PMID- 14666759
TI  - [Clinical observation on the efficacy enhancing and toxicity attenuating effect
      of nuzhen yangyin granule to the anti-parkinsonism therapy mainly with Medopa].
AB  - OBJECTIVE: To observe and assess the efficacy enhancing and toxicity attenuating
      effect of Nuzhen Yangyin Granule (NYG) to the anti-parkinsonism (paralysis
      agitans) therapy with Medopa and Artane. METHODS: Adopting the randomized double
      blinded method, the effect of adding NYG to 30 patients with Parkinsonism in the
      treated group, who already received anti-Parkinsonism treatment but showing
      decreased response to Medopa and Artane and with obvious adverse reaction, was
      observed and controlled by 30 patients treated by adding placebo. RESULTS: The
      total effective rate in the treated group and the control group was 86.7% and
      56.7% respectively, the total syndrome improving rate was 90% and 56.7%
      respectively and the toxicity attenuating rate 90% and 43.3% respectively,
      comparison between the two groups showed significant difference (P < 0.05 or P <
      0.01). NYG also showed markedly effective in reducing the adverse reactions of
      Medopa and Artane on digestive, neuro-psychiatric and cardiovascular system.
      CONCLUSION: NYG has obvious efficacy enhancing and toxicity attenuating effects
      caused by the anti-Parkinsonism treatment with Medopa and Artane.

PMID- 14666760
TI  - [Clinical study on effect of yuantong capsule in treating vascular dementia].
AB  - OBJECTIVE: To observe the clinical effect of Yuantong Capsule (YTC) in treating
      vascular dementia (VD). METHODS: Eighty-three patients of VD were randomized on
      ratio of 2:1 into two groups, the 54 patients in the treated group were treated
      with YTC orally administered, 3 times a day, 1 capsule in each time. The
      remaining 29 patients in the control group were treated with Hydergine orally, 3
      times a day, 2 mg in each time. The therapeutic course for both groups was 2
      months. RESULTS: The therapeutic effect in the treated group was significantly
      better than that in the control group, significant difference (P < 0.05 or P <
      0.01) was shown in comparison of the two groups in terms of the mini-mental state
      examination (MMSE) and activity of daily living (ADL) test, symptoms scoring,
      total effective rate, and laboratory indexes findings. CONCLUSION: The
      therapeutic effect of YTC in treating VD was obvious.

PMID- 14666761
TI  - [Clinical study of yishen jianpi yangxue tongli therapy in treating polycystic
      ovary syndrome].
AB  - OBJECTIVE: To observe the effect of Yishen Jianpi Yangxue Tongli Therapy (YJYTT)
      in treating polycystic ovary syndrome (PCOS) and to explore the therapeutic
      mechanism of YJYTT. METHODS: One hundred and seven PCOS patients with syndrome
      differentiation of TCM as Pi-Shen Yang deficiency were randomly divided into two
      groups, the treated group (n = 76) was treated with Chinese herbal medicine,
      while the control group (n = 31) was treated by clomiphen. The therapeutic effect
      in both groups and the change of body mass index (BMI), Ferriman-Gallway (F-G)
      score, serum sex hormones and serum oral glucose tolerance test (OGTT) before and
      after treatment were observed. RESULTS: The comparison of total effective rate
      between two groups was insignificantly different, but the pregnancy rate of the
      treated group (65.7%) was markedly higher than that of control group (25.0%, P <
      0.01). Also, significant difference was shown in the aspect of BMI, F-G score,
      serum testosterone (T), luteinizing hormone (LH) and OGTT, etc. between the two
      groups (P < 0.05). CONCLUSION: The YJYTT could markedly improve the clinical
      symptoms and pregnancy rate of PCOS patients, particularly showing good effect to
      the clomiphen resistant patients. The mechanism possibly was due to its
      regulation on hypothalamus-pituitary-ovarium axis and reducing the insulin
      resistance.

PMID- 14666762
TI  - [Randomized controlled clinical study on effect of Chinese compound changjitai in
      treating diarrheic irritable bowel syndrome].
AB  - OBJECTIVE: To verify the clinical efficacy and safety of the proven Chinese
      Compound Changjitai (CJT), in treating the diarrheic irritable bowel syndrome
      (DIBS). METHODS: Randomized controlled open clinical trial design was adopted, 45
      patients were randomly divided into two groups, CJT and pinaverium bromide (PVB)
      were given as treated and control agent respectively. IBS scoring system (BSS),
      defecation state questionnaire (DSQ) were used to record the changes of the
      patients' main symptoms before and after treatment. RESULTS: The total effective
      rate of CJT group was 83.3%, while that of PVB was 73.3%. CJT was superior in
      efficacy to that of PVB in improving stool quality, reducing defecation episodes
      of diarrheic patients, alleviating tenesmus symptoms, decreasing bellyache days
      and ameliorating abdominal distention. Any drug-related adverse reaction was not
      seen. CONCLUSION: The efficacy of CJT in treating DIBS is definite and without
      any toxic and adverse effects.

PMID- 14666763
TI  - [Clinical observation on treatment of diabetic peripheral neuropathy with qi
      supplementing and blood-activating therapy].
AB  - OBJECTIVE: To observe the clinical efficacy of Qi-supplementing and blood
      activating (QSBA) in treating diabetic peripheral nephropathy (DPN). METHODS:
      Sixty-eight type 2 diabetes mellitus patients with Qi deficiency-blood stasis
      Syndrome were randomly divided into two groups, the neurotrophic agents were used
      in both groups, while QSBA herbs were used in the treated group additionally. The
      treatment course was 2 months. Blood glucose (BG), triglyceride (TG), total
      cholesterol (TC) and nerve conduction velocity (NCV) were detected before and
      after treatment. RESULTS: After treatment, the BG, blood lipid, NCV were improved
      significantly (P < 0.05) in both groups, but the improvement was more significant
      in the QSBA treated group than in the control group (P < 0.05). CONCLUSION: QSBA,
      in treating DPN, can not only improve its symptoms, but also ameliorate the NCV.

PMID- 14666764
TI  - [Clinical observation on xiehuo yangyin powder in treating 30 initial stage of
      toxic and diffuse goiter patients].
AB  - OBJECTIVE: To observe the therapeutic effect of Xiehuo Yangyin powder (XHYY) in
      treating the initial stage of toxic and diffuse goiter (Graves' disease).
      METHODS: Sixty patients were randomly divided into two groups, the treated group
      (n = 30) was treated with XHYY and methimazole, while the control group (n = 30)
      was treated with methimazole alone. The TCM syndrome score and thyroxin level in
      the two groups were compared and analyzed before, and 2 weeks, 12 weeks after
      treatment. RESULTS: The syndrome score and thyroxin level in the treated group 2
      weeks, 4 weeks, 12 weeks after treatment were reduced in comparing with before
      treatment, with the improvement better than those in the control group in the
      corresponding stages (P < 0.05). CONCLUSION: The Chinese herbal medicine XHYY
      plus methimazole, in treating Graves' disease, could rapidly and effectively
      improve the patients' clinical symptoms and lower the thyroxin level, reduce the
      daily taken of methimazole.

PMID- 14666765
TI  - [Therapeutic effect of qingyi decoction and tetrandrine in treating severe acute
      pancreatitis in miniature pigs and serum drug level determination].
AB  - OBJECTIVE: To investigate the therapeutic effect of Qingyi Decoction (QYD) and
      tetrandrine (Tet), used singly or combind, in treating miniature pigs with severe
      acute pancreatitis (SAP) and its mechanism. METHODS: Thirty-two Guizhou miniature
      pigs were made into SAP model by pancreatic duct retrograde injection of 5%
      sodium taurocholate. They were randomly divided into 4 groups: the control group,
      the QYD group, the Tet group and the combined treated group. The serum amylase
      activity and interleukin-1 and 6 (IL-1, IL-6) contents in serum from vena cava
      and portal vein were tested by biochemistry and radioimmunoassay (RIA). Serum
      emodin and plasma Tet levels were measured by high performance liquid
      chromatography (HPLC) 24, 48 and 72 hrs after treatment. And the pathological
      changes of pancreas, lung and liver were observed under microscope. RESULTS: The
      mortality of SAP pigs was reduced significantly and the inflammatory injury of
      the organs was ameliorated obviously in all treated groups, and the increased
      amylase activity and IL-1, IL-6 levels was attenuated. The therapeutic effect was
      much more obvious, and the plasma Tet level at different time points were much
      higher in the combined treated group than those in the other two groups treated
      by single drug (P < 0.01). CONCLUSION: Both QYD and Tet could treat effectively
      SAP through multiple pathways, combination of them reveals an elevation of serum
      drug concentration and shows a synergistic effect.

PMID- 14666766
TI  - [Comparative study on the regulatory effects on senescence related cell cycle
      gene expression by TCM principles of tonifying shen, invigorating pi benefiting
      qi, and activating blood circulation].
AB  - OBJECTIVE: To compare the effects of TCM therapeutic principles of tonifying Shen
      (TS), benefiting Qi (BQ), invigorating Pi (IP) and activating blood circulation
      (ABC) herbs in regulating the gene expression in senescence related cell cycle.
      METHODS: Drug sera containing TCM herbs of the above-mentioned principles were
      used to treat the aged human diploid fibroblast cell line 2BS. The effect of TCM
      on the senescence related cell cycle and its related gene expression (P16INK4,
      Cyclin D1 and PCNA) were examined by means of cell proliferative doublings, flow
      cytometry, RT-PCR and Western blot analysis. RESULTS: TCM herbs of TS and BQ
      could improve the cell cycle, down-regulate the P16 and Cyclin D1 mRNA/protein
      expression, up-regulate PCNA mRNA/protein expression, while TCM herbs of IP and
      ABC showed insignificant effect on these indexes. CONCLUSION: TCM herbs of TS and
      BQ have effect in improving cell cycle, it may be achieved through promoting the
      P16 pathway of gene expression.

PMID- 14666767
TI  - [Effect of supplemented danggui shaoyao powder and its disassembled prescriptions
      on lymphocytes proliferation in aged rats].
AB  - OBJECTIVE: To study the effect of supplemented Danggui Shaoyao San (DSS) and its
      disassembled prescriptions on function of lymphocyte in aged rats. METHODS: Rats
      aged 18 months were administered with decoction of DSS and its disassembled
      prescriptions separately in groups for 3 weeks to prepare drug containing serum.
      Samples of ConA induced rats splenic lymphocytes proliferation was treated
      respectively with prepared drug serum, for testing their effect on lymphocyte
      proliferation using methyl thiazolyl tetrazolium (MTT) method, and isoprel (ISO)
      and propranolol were taken as the controls. RESULTS: The A value of lymphocyte
      proliferation in the drug serum treated groups was significantly different from
      that in the control groups (P < 0.01), which could be reduced markedly after
      treatment with ISO, but could restore to the level before ISO treatment by adding
      drug serum or propranolol. CONCLUSION: DSS and/or its disassembled prescriptions
      could raise the lymphocyte proliferation in aged rats significantly, it also
      shows antagonizing effect against the inhibition of ISO on lymphocyte
      proliferation.

PMID- 14666768
TI  - [Experimental study on expression of GM-CSF from human endothelial cells and
      monocytes induced by total saponins of panax ginseng].
AB  - OBJECTIVE: To study the effect of total saponins of Panax ginseng (TSPG) on the
      expression of granulocytemacrophage colony-stimulating factor (GM-CSF) from human
      endothelial cells and monocytes and the relationship between TSPG and human
      granulocytopoiesis and monocytopoiesis modulation. METHODS: Adopting the
      hematopoietic progenitor cells culture in vitro, hematopoietic growth factor
      biological assay, immunocytochemistry and nucleic acid in situ hybridization, the
      GM-CSF expression in the endothelial cells and monocytes were detected. RESULTS:
      The conditioned cultural media of endothelial and monocytes induced and prepared
      by TSPG, could significantly promote the proliferation and differentiation of
      human colony forming unit-granulocyte macrophage (CFU-GM), and enhance the
      protein and mRNA expression of GM-CSF in endothelial cells and monocytes.
      CONCLUSION: TSPG could possibly through direct or indirect route, promote
      hematopoietic, induce endothelial cells and monocytes in the microenvironment to
      synthetize and secrete GM-CSF, so as to further promote the proliferation and
      differentiation of human CFU-GM.

PMID- 14666769
TI  - [Preliminary study on effects of Trichosanthes kirilowi root on hela cells].
AB  - OBJECTIVE: To investigate the cytotoxic effect of extracts of Trichosanthes
      kirilowi (TK) root on Hela cells in vitro and its probable anti-tumor mechanism.
      METHODS: The cytotoxic effect in vitro on the growth of Hela cells was evaluated
      by microculture tetrazolium assay (MTT). Cell ultrastructural changes were
      examined by scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM), and DNA agarose electrophoresis was performed to determine
      apoptosis and biochemical changes of Hela cells. RESULTS: Exposure of Hela cells
      to TK extracts for 24-48 hrs resulted in a cell growth arrest, which showed in a
      time- and dose-dependent manner (r > 0.880, P < 0.01). With SEM and TEM, marked
      changes were observed, including microvilli disappearance or reduction, cell
      membrane vesiculation, cell shrinkage, condensation of chromosomes and apoptotic
      bodies with complete membrane. Besides, the apoptosis of Hela cells was confirmed
      by typical DNA ladder formation on gel electrophoresis. CONCLUSION: Extracts of
      TK has a marked anti-tumor activity and could induce apoptosis of Hela cells.

PMID- 14666770
TI  - [Review of the relation between polymorphism of genes and TCM syndrome
      differentiation].

PMID- 14666771
TI  - [Some opinions on the integrative Chinese and Western medical study of diabetes
      mellitus].

PMID- 14666772
TI  - [Clinical observation on treatment of children spastic cerebral palsy by combined
      therapy with acupuncture, moxibustion, massage and bacillus botulinus type A].

PMID- 14666773
TI  - [Observation on effect of qi-supplementing blood-activating and stasis-removing
      principle in treating patients with systemic lupus erythematosus of blood-stasis
      type].

PMID- 14666774
TI  - [Clinical observation of bianbiqing on the effect of colonic transit time in
      constipation patients with asthenia syndrom].

PMID- 14666776
TI  - [Discussion on the English translation of the TCM terms of "wind, cold, hotness,
      damp, dryness and fire"].

PMID- 14666777
TI  - [Analysis on the writings published in the garden of basic level in the CJIM].

PMID- 14666775
TI  - [Influence of luyoutal on serum cytokines in patients with depression].

PMID- 14666778
TI  - [Regulatory action of Chinese herbs on the signal transmission abnormality in
      oncogenesis].

PMID- 14666779
TI  - [Prevalence of hepatitis B and C viruses in a chronic hemodialysis center in
      Dakar].
AB  - In endemic areas of hepatitis B and C, hemodialysis patients are highly exposed
      to these infections. So the authors studied the prevalence of hepatitis B and C
      viruses among chronic hemodialysis patients of CHU A. Le Dantec of Dakar in a
      cross study carried out from June 1996 to June 1997, in order to identify risk
      factors and suggest appropriate prophylaxis. The study concerned fifteen chronic
      hemodialysis patients in an unit of hemodialysis in Dakar. For each patient,
      clinical and biochemical data were collected serological markers of B and C
      viruses were tested and HCV-RNA in case of seropositivity to C virus. The mean
      age of patients were 48 years and average duration of hemodialysis was 40 months.
      Hepatic injury was silent in all cases. Only one patient (6.7%) was AgHBs carrier
      while 9 patients (60%) were positive for antibodies anti HBs without previous
      hepatitis B vaccine. Twelve patients (80%) were found to be HCV-antibody positive
      and half of them were HCV. RNA positive. Average value of alanine amino
      transferase was higher in HCV-viremic patients than in seropositive but non
      viremic patients, although normal. Genotype 2 ac was found in 3 HCV viremic
      patients but it could not be determined in 3 other patients. Hemodialysis
      duration and number of blood transfusions were found to be risk factors of HCV
      infection. The high prevalence of HCV seropositivity among chronic hemodialysis
      patients in Dakar has led to strengthen precautions in our hemodialysis unit. HCV
      serological screening in blood donors is advocated.

PMID- 14666780
TI  - [Tetanus: epidemiological aspects at the Infectious Disease Clinics at the Fann
      University Hospital Center in Dakar].
AB  - This retrospective study was carried out to assess the recent epidemiological
      aspects of tetanus in Senegal. Based on the records of tetanus cases admitted at
      the Infectious Diseases Clinic in Dakar over a 7-year periode (1990-1996), this
      study showed that tetanus is still a major public health concern in Senegal. A
      global prevalence rate of 18.8% was found. Portals of entry were noticed to be:
      dirty wounds (48%), the umbilical stumps (19%), non sterile intra-muscular
      injections (4.5%), surgery (3.3%) and traditional practices (4.2%). Nevertheless,
      in a high proportion of cases (13.3%), the portal of entry was not found. A 30.3%
      case fatality rate was observed, that varied significantly according to portals
      of entry, reaching 60.4% in umbilical tetanus. It is recommended here that the
      immunization programme against tetanus be reinforced and supported by I E C
      Strategies together with retraining of medical personnel.

PMID- 14666781
TI  - [Lumbar hernia through the Jean Louis Petit triangle: anatomic and clinical
      aspects].
AB  - Lumbar hernia through Jean Louis Petit Triangles is rare. Usually asymptomatic,
      it is sometime revealed by lumbar mass or a complication. Surgical treatment
      consists on parietal repair. This could be done by direct suture, muscular plasty
      or prothetic material. We hereby, report three cases of lumbar hernia. We get the
      opportunity to make an update in the anatomical, clinical and therapeutical point
      to view.

PMID- 14666782
TI  - [Scintigraphic aspects of thyroid nodules investigated at the University Hospital
      Center of Dakar].
AB  - The authors studied the scintigraphical appearances of thyroid nodules. This
      study on 8 years period enabled the authors to list 876 thyroid nodules. The
      scintigraphy shows: 14.05% of isofixant nodules, 10.73% of "hot" nodules, 58.44%
      of "cold" nodules, 16.78% of heteromultinodular goitries. The scintigraphy proved
      its great importance as in the diagnostic as in the way of therapy of this
      pathology.

PMID- 14666783
TI  - [Conduction disorders in chronic parietal endocarditis or endomyocardial
      fibrosis. 170 cases at the Cardiology Institute of Abidjan].
AB  - The authors have conducted research on conduction disturbances in the
      endomyocardial fibrosis, synonymous with chronic parietal endocarditis, about 170
      cases at the Institute of Cardiology in Abidjan, from January 1977 to June 1991.
      The anatomical and/or angiographic examination have permitted to describe 64
      cases of right fibrosis, 24 cases of left fibrosis and 82 cases of bilateral
      fibrosis. Conduction anomalies have been observed among 42.9% of the patients.
      Among 92 anomalies recorded, the most frequent has been the first degree heart
      block (43.5%) and the incomplete right bundle branch block (30.4%). The old age
      of the patients and the right localization were the factors associated with
      conduction disturbances in endomyocardial fibrosis (difference not significant).
      Yet, fibrosis surgery, especially the decortication of the fibrous endocardium of
      the right ventricle, have generated one or many conduction anomalies among most
      of our operated patients. The right branch of the fasciculus of the His has been
      the most injured by the fragmented techniques of METRAS who had, therefore, the
      merit to have minimized the incidence of the complete post-operative heart blocks
      still high in European and Brazilian series. In term of prognosis, no conduction
      disturbance has directly caused a patient's death, even if those anomalies cannot
      be totally ruled out in the 16 cases of sudden death.

PMID- 14666784
TI  - [Microbiological quality of street-vendor ice cream in Dakar].
AB  - During a multicenter study initiated by the International Network of Pasteur
      Institutes and Associated Institutes, microbiological quality of street-vended
      ice creams in Dakar was evaluated. 313 samples of ice creams from 170 street
      vendors were collected and tested for common foodborne pathogens and indicator
      organisms. Results showed that microbiological quality of 45% of tested samples
      was unsatisfactory because of large populations of aerobic mesophilic organisms
      (36.7%), thermotolerant coliforms bacteria (21.4%) and sometimes E. coli.
      (10.6%). Strict pathogens as Salmonella, Shigella and Vibrio cholerae were not
      found. An investigation conducted among vendors showed a lack of education and
      training; these vendors need information about food preparation and storage
      practices that reduce microbiological contamination of foods.

PMID- 14666785
TI  - [Vascular parkinsonian syndrome in 21 case studies, two of which were anatomic].
AB  - A clinicopathological study of parkinsonian syndrome witch occurred after stroke,
      is done by the authors. That is a retrospective study concerning 2 anatomic cases
      from 21 vascular parkinsonism. All the patients were admitted in the clinique
      neurologique de Fann from 1970 to 1990. They were 15 men and 6 women. Their age
      ranged between 45 to 75 years (mean 59.66). The 2 autopsied cases had lesions
      located in the thalamus as the superior part and a discreet cortical atrophy in
      the one case, and in the other case, we can see similar lesions in the right
      external capsule and in the inferior part of the putamen. Another lesion of
      haemorrhage infarct was located in the left temporal lobe. The locus niger was
      macroscopically normal in the 2 cases. Anatomical lesions observed have been
      localized in the putamen and in the external capsule in the associatical cerebral
      cortex in the second case and in the first one, lesions are located in the
      thalamus and in the cortex. These lesions were not well correlated with
      neurological signs. The different clinical aspects are discussed. From this
      study, it results that arterial damages associated with hypertension and
      atheromatosis might touch dopaminergic structures responsible of parkinsonism
      with sometime good sensitivity to levodopa.

PMID- 14666786
TI  - [Serum cortisol level variations in thyroid diseases].
AB  - This work studies the thyroid disorders impact on adrenals glands by measuring
      total cortisol. Radioimmunoassays of thyroid hormones and cortisol were performed
      in 108 subjects, aged 20-52 years, with thyroid diseases. Our results show low
      cortisol values (80.35 nmol/L) in 4.77% of hyperthyroids, high values in 3.57% of
      hyperthyroids (1348.18 nmol/L) and 12.5% of hypothyroids (969.05 nmol/L). In
      hyperthyroidism, thyroid hormone stimulates the secretion of 11 ceto metabolites
      biologically inactive, unable to slow pituitary activity, inducing an increased
      production of endogene cortisol. Excessive catabolism can lead to the exhausting
      of overstimulated adrenal glands, and therefore to a decreased cortisol. In
      hypothyroidism, high cortisol results of increase cortisol half life and decrease
      of metabolic clearance. Control mechanisms often allow normal cortisol values.
      These alterations in functional activity of adrenal glands, seen in nearly 10% of
      these subjects, sometimes command a specific attitude in diagnosis and therapy.

PMID- 14666787
TI  - [Adnexal masses in the Surgical Clinic of the University Hospital Center of
      Dakar, 74 cases].
AB  - The aim of this study was to assesss epidemiological, clinical and the
      therapeutic aspects of annexial masses. We have performed a retrospective study
      from 15/09/1994 up to 31/12/1997 including 74 patients. The prevalence rate was
      18.40% of the overall gynecologic surgery in our department. Mean age was 36
      years old. The range 30-41 years represented 40.5% of our cases. The mean gestity
      was 4 and the average parity 4. The most common clinical features were pelvic
      pains (75.57%) and hypogastric masses (50%). The duration of the disease ranged
      from 1 to 10 years. The general status was good in 94.59% of cases, bad with
      ascites in 5.41%. The annexial masses were cystic in 87.83%. The ovarian cysts
      were located at the both sides in 45.94, and bilateral in 8.10%. The annexial
      masses were solid in 9.45%. An abscess was found in 6.75%. We have performed an
      annexectomy in 66.1% and a cystectomy in 16.21%. The post operative complications
      were wound suppuration in 13.51%. The mortality rate was 1.35%. At the long-term
      follow up we have noticed an eventration in 1.35% and a recurrence with need of
      reintervention in 16.21%. The pathologic exam found a benign tumor in 95.16% and
      a carcinoma in 4.84%. The annexial masses are very common in our practice. They
      involve young multipare women. The main clinical outcome is pelvic pains.
      Annexectomy is the principal treatment.

PMID- 14666788
TI  - [Vulvar cancers. Retrospective study of 23 cases at the Cancer Institute of
      Dakar].
AB  - The vulvar cancer is an uncommon disease which is beginning mostly on vulvar
      intraepithelial neoplasma and it keeps a very bad prognostic. The purpose of this
      study is to report the epidemiological, the anatomo-clinic and and to discuss the
      treatment. We tell about 23 vulvar cancer from 1956 to 1995 which were followed
      at the cancer Institut of Dakar. The mean age of patients is 47 years and they
      are on menopause in 78.6%. The most of the tumors are ulcerate (96%). The
      clinical investigation find according the staging of FIGO: 15 tumors (T2), 8
      tumors (T3), 6 tumors (N1), 9 tumors (N2) and 1 tumor (M1b). The surgery is the
      principal treatment with 6 radical vulvectomy and 17 palliative vulvectomy. The
      surgery was associated with radiotherapy and chemotherapy. So the vulvar cancer
      is uncommon in our country and concern the young wives. The vulvectomy with
      lymphadenectomy is the principal treatment; the prognostic still very bad because
      the diagnostic is often later.

PMID- 14666789
TI  - [Partial laryngectomies at the University Hospital Center of Dakar].
AB  - Our experience on partial laryngectomies stretched on a period of 16 years. In an
      unfavorable medical environment, we issue our indicative criteria throughout this
      experience. From January 1st 1981 to December, 31st 1996, 14 patients have had a
      partial laryngectomy in University Hospital Center of Dakar. The average year was
      56 and the sex-ratio was 1 woman out of 13 men. There were 13 carcinomas and 1
      cas of acute dysplasia. 4 patients have had vertical partial laryngectomy, 5 have
      had a horizontal partial laryngectomy and 5 a partial laryngectomy on the upper
      out of the cricoid cartilage with the ganglia. After a 3 years close look, on 10
      patients, we noted that 1 died, 1 disappeared, and 8 still were living.
      Carcinological failures consisted in 3 development by stages and 1 cas of a 2nd
      localisation. As for as functional results, the removal of the nozzle and the
      elimination of the nasogastric grohe of supply, were effective for respective
      average allotted time of 11 and 12 days. This laryngeal partial surgery seem
      scarce in our practice (12% of the patient who have had it). The improvement of
      results go to the choice of indications, the information the formation and the
      acquisition of technical stools more efficient.

PMID- 14666790
TI  - [Tetanus osteoarticular complications in Dakar].
AB  - To assess the epidemiological and clinical features of osteoarticular symptoms
      during tetanus infection, we carried out a retrospective study in infectious
      Diseases Ward of the University Teaching Hospital in Dakar (Senegal). Over a
      period of 7 years (1990-1996), 1, 199 cases of tetanus of more than 1 month of
      age were diagnosed. Among those who survived (n = 948), 18 cases of osteo
      articular manifestations were observed (1.8%): 15 presented with vertebral
      fracture located within the thoracical part T4-T8 (83.3%) while 3 patients had
      para-articular osteoma in the elbows (16.7%). These complications occurred on
      stage II (89%) and stage III (11%) of Mollaret's classification of tetanus
      infection. Males were more represented than females (sex-ratio = 5) and the
      median age was 13 years (range = 6-45 years). The mean hospitalisation duration
      was significantly higher for patients with para-articular osteoma (6 weeks) than
      for those with vertebral fracture (3 weeks). No major functional impairment was
      noticed during hospitalisation and patients required only physiotherapy and
      clinical and radiological surveillance. Although not frequent and of some little
      functional consequence, osteoarticular complications of tetanus, should invite to
      improve the antitetanic immunization strategies in developing countries.

PMID- 14666791
TI  - [Protein-energy malnutrition in children less than five years old in a rural zone
      in Senegal (Khombole)].
AB  - A survey on 400 children less than five years old living in three villages of the
      sanitary district of Khombole has been realized from 17th to 25th April 1997 in
      order to evaluate the existence of malnutrition and the hazard factor linked to
      it. All children have been weighed and measured. The paraclinic assessment made
      up by a rate of haemoglobin and a parasitical test of the, motions have been
      realized on 275 children. The emaciation concerns 8% of the children and the
      statural backwardness 34.7% of them. The malnutrition is variable from one
      village to another. The percentage of children suffering from a severe
      malnutrition according to the classification of Gomez concerns 4.5%. Geophagy,
      intestinal parasitosis, and anaemia are closely related to chronic malnutrition.
      The results show the existence of a precarious nutritional situation in rural
      area requiring new policies of struggle against malnutrition.

PMID- 14666792
TI  - [Infections in Senegalese children and adolescents with sickle cell anemia:
      epidemiological aspects].
AB  - Infection is the main factor of morbidity and mortality in children with sickle
      cell disease (SCD). The objective of this study is to determine it's
      epidemiologic outline in senegalese children and adolescents with SCD. We
      retrospectively studied infection data in all the charts of a cohort of 323
      patients with SCD (307 SS, 13 SC and 3 s beta + thalassemia) followed at Albert
      Royer children hospital from january 1991 to december 1997. Serum sampling was
      systematically made for HIV and antigen HBs serology in all patients we received
      in the last 3 months (october to december 1997). Patients were aged from 5 months
      to 22 years (medium age = 8 years). 813 infection episodes were diagnosed,
      concerning 184 patients (56 per cent). SS patients were more affected (59 per
      cent) than the others (23 per cent, p = 0.04). ENT and broncho-pulmonary onsets
      were more frequent but had a generally benign course. Menigitidis, septicemia and
      osteomyelitis were exclusively diagnosed in SS patients. Their prevalences in
      this group were respectively: 1.0 per cent, 4.9 per cent and 9.8 per cent. HIV
      serology was determined in 155 patients, including 41 per cent with blood
      transfusion antecedents. All tests were negative. HBs antigen was determined in
      104 patients and seroprevalence was 7.7 per cent in the whole group and 6.0 per
      cent in patients with transfusion antecedents and 7.7 per cent for the others.
      Plasmodium falciparum malaria onset was observed in 9.6 per cent of our patients
      and there was no case of cerebral malaria. Infection was involved in 9 of the 11
      cases of death. Then infection constitute the major problem in children and
      adolescents with SCD in Dakar. However prevalences of severe onsets are
      comparable to data in Europe despite our poor follow up conditions. Senegal
      haplotype may lead to a good tolerance of SCD. Negative HIV serology and low HBs
      antigen seroprevalence in transfused patients are attributed to a relatively low
      level of HIV prevalence in the general population and a good transfusion security
      in Senegal.

PMID- 14666793
TI  - [Urinary tract infections in Dakar: etiologies, therapeutic basis].
AB  - This prospective study, performed in Fann University Teaching Hospital from
      January 1st to December 31st 1998, concern 1446 samples of urine. Enterobacteria
      (87.56%) were the most frequent aetiology, and Escherichia coli (48.7%) was the
      leading species in this family. The strains of E. coli present more resistant
      profil to beta-lactams (70.27%). Fluoroquinolons are active on more than 80% of
      the strains responsible of urinary tract infection in Dakar.

PMID- 14666794
TI  - [Etiologies of chronic renal insufficiency in a adult internal medicine service
      in Dakar].
AB  - Chronic renal failure (CRF) sets public health problems both as its prevalence
      and its morbidity. The treatment is costly, that's why developing countries must
      engage in preventive strategies. In this view, a retrospective study was led in
      Le Dantec Hospital from January 1st, 1998 to December 31st 1993. As a preliminary
      to a countrywide survey, it is necessary to find out the causes of CRF clarify
      the causes of CRF in a hospital setting and sketch out a preventive strategy. The
      patients included in this study were those with CRF. The diagnosis of CRF were
      based on medical history data, anemia, but mainly biological and ultrasound
      imaging: creatininima more than 18 mg/l, and/or creatinine clearance less than 80
      ml/mn, whose diagnosis was little sized kidney. Of the 5276 in patients, 384 had
      CRF representing 7% of sample. Only 261 cases were retained broken down into 119
      females and 142 males (sex-ratio: 1.19). Age span ranges from 15 to 88 years with
      a mean of 44 years. Etiologies were dominated by unknown causes, 89 cases
      (34.23%). Nephroangiosclerosis was the most common known cause, 65 cases (25%)
      followed by diabetes nephropathy with 54 cases (20.69%) and chronic
      glomerulonephretic representing 41 cases (15.76%). Other causes were identified
      in various proportions: cortical necrosis (4 casesa, hereditary nephropathies (2
      cases), interstitial nephropathy (1 case), nephroponophteois, kidney
      polykystosis, prostate adenoma and bilharziosis were all found in one case each.
      This study pointed out to a need for a nation-wide survey to define the
      aetiologies of CRF. The study also showed that an early diagnosis and adequate
      treatment of high blood pressure, diabetes and GNC should certainly constitute
      the principal axes of investigation for prevention.

PMID- 14666795
TI  - [Epidemiological and therapeutic aspects of rectal cancer in Senegal: 74 cases at
      the Cancer Institute of Dakar].
AB  - Through a retrospective study of 74 cancer of rectum the autors determine the
      epidemiology, the anatomic appearance and discuss the treatment, the prognostic.
      The mean age of patients was 48 years and the Duke's staging found: 16 stages B,
      46 stages C and 12 stages D. The pathological anatomy showed: 58 adenocarcinoma,
      9 colloidal adenocarcinoma, 4 epidermoidal carcinoma, 2 lymphosarcoma, 1
      anaplasic adenocarcinoma. The operability rate was 66.2%, the resectability was
      40.8% and the sphincteral preserving was 8.1%. The radiotherapy preceded the
      surgery in 6 cases and associated the chemotherapy. The chemotherapy preceded the
      surgery thein 14 cases and succeeded in 2 cases. The mortality was 24.4% and the
      recidivation 35%. The global survival 5 years was 32%. The prognostic could
      better by an earlier diagnostic and a multidisciplinary treatment.

PMID- 14666796
TI  - [Cancers of the anus: 32 cases].
AB  - The purpose of this retrospective study about 32 anal carcinoma was to determine
      the epidemoilogy, to discuss the therapeutic indications. The mean age of
      patients was 56.42 years and the protologic antecedent was 14%. According to the
      clinical staging: 1 patient was T1, 2 T2, 19 T3, 10T4; 1 No, 2 Nx, 7 N1, 10 N2,
      12 N3; 25 M x, 5 MO, 2 M1. The histologic classification of OMS found: 17
      epidermoid carcinoma, 12 glandular carcinoma, 1 transitional cell carcinoma, and
      1 non classify cancer. 14 radical resection and 3 local resection were realised,
      8 patients had an exclusive radiotherapy: 2 curative radiotherapy and 6
      palliative. The morbidity was 9.37% and dominated by perineal suppuration and the
      mortality was 3.12%. The adjunctive radiotherapy must be the first treatment of
      the anal cancer in our countries.

PMID- 14666797
TI  - [Protein profile of Senegalese children presenting with nephrotic syndrome].
AB  - In Senegal, nephrotic syndrome usually occurs upon malnutrition that confers it
      its specificity and has brought us to establish the proteinic profile of
      Senegalese children suffering from it, in the aim to improve its treatment.
      Twenty children on the average of six years, hospitalized for nephrotic syndrome,
      were chosen. They were compared to 20 healthy children of the same age group, and
      20 other children hospitalized for a non-renal inflammatory syndrome. For each
      subject were dosed total blood proteins and albumin. The protein electrophoresis
      has permitted to evaluate the alpha-1, alpha-2, beta and gamma globulins. We have
      observed predominance of boys with a 2.33 sex ratio. Our patients presenting a
      nephrotic syndrome were about six years old; no case has been noted before two
      years. Total proteins and albumin have decreased respectively to 52.10 g/l and 16
      g/l. This diminishing is essentially linked to the massive urinary escape of
      plasmatic proteins and would explain partly the increase of lipids. The alpha-1
      globulins were equally lowered but the alpha-2 globulins were increased by 40% of
      total proteins. Beta globulins have decreased, following the evolution of gamma
      globulins. In Senegal, The early age of nephrotic syndrome occurrence and the
      biological perturbations of the proteinic profile, recommend global and quick
      treatment considering food recovery and nutrition. The correction of these
      parameters being able to constitute in one hand an element of accessible and
      reliable supervision, and one the other hand the basis of complete treatment.

PMID- 14666798
TI  - [Guillain-Barre syndrome in children: experience in the neurology service of
      Dakar].
AB  - A retrospective survey has been conducted from january 1979 to january 1999 about
      the young inpatients file records of the department of neurology of Dakar. 19
      cases of Guillain-Barre's syndrome have been collected, representing 2.3% of the
      children admitted in the department of neurology. The children were 18 months to
      16 years old. The sex ratio was 1.4. Infectious disease has been reported in
      68.4% of the cases during the 4 weeks preceding the neurological features. The
      notion of vaccination was found in 5.3% of the cases. The motor deficit was
      frequent, represented by paraparesis in 63.2% and quadriparesis in 36.8% of the
      cases. The mean duration of the hospitalisation was 28 days. 52.6% of the
      patients have completely recovered from their motor deficit and this recovery was
      unachieved in 36.8%. No fatal event has been detected. The therapeutical means
      were represented by vitaminotherapy B1B6B12 associated with kinesitherapy. Our
      results reveal a less severe evolution and better prognosis of Guillain-Barre's
      syndrome affecting children, instead of the absence of more appropriate means of
      treatment such as plasma exchange and intravenous immune globulin.

PMID- 14666799
TI  - [Epidemiological factors, treatment and prognosis of uterine sarcomas: 14 cases
      at the Cancer Institute of Dakar].
AB  - The study of uterus sarcoma took in interest because these tumors were
      unrecognized and sat nowadays many questions. The purpose of this study is to
      review the epidemiological factors, the problems of treatment and prognostic of
      uterus sarcoma. It's a retrospective study of 14 sarcomas of uterus reported from
      1959 to 1997. The mean age of the patients was 54 years and they were on
      menopause in 78.6%. The clinical investigation found according the FIGO staging:
      6 stage I (42.6%), 4 stage II (28.4%), 1 stage III (7.1%) and 3 stage IV (21.4%).
      The leiomyosarcoma (42.6%) appeared as the more frequent histologic lesion.
      Surgery was the principal treatment: it was alone on 3 cases (24.9%), associated
      with chemotherapy on 8 cases (66.8%) and one patient had an association surgery,
      chemotherapy and radiotherapy. The global survival was 21.4% at 2 years and all
      the patients were dead at 5 years and it seemed that it would be better when the
      patients were treated by radical surgery associated with chemotherapy and
      radiotherapy.

PMID- 14666800
TI  - [Cri-du-chat syndrome. A case report].
AB  - We report a documented case in Senegal with cri-du-chat syndrome diagnosed in a 3
      months old girl. Our patient benefited from clinical examination, ECG (15
      derivations), chest X ray and standard laboratory tests. The cry has been
      recorded on a magnetic band. We performed also a pulsed-Doppler, two dimensional
      and TM echocardiography. Chromosomal analysis has been realized. These data are
      discussed and compared to the literature. At admission this patient presents
      characteristic cat like cry. At examination, there is a facial dysmorphy,
      important growth retardation and feeding dyspnea. Auscultation shows a 3/6 left
      sub-clavicular systolic murmur. Laboratory tests show anemia (hemoglobin = 7.8
      g/dl). Chest x-ray showed a cardio-thoracic ratio at 0.61 with increased
      pulmonary vascular markings. ECG showed right ventricular hypertrophy.
      Echocardiography-Doppler revealed persistent ductus arteriosus (PDA). Chromosomal
      analysis shows deletion of the short arm of chromosome 5. After treatment with
      digitalis and diuretics there was an improvement of cardiac failure. Diagnosis of
      cri-du-chat syndrome is easy when characteristic cat-like-cry is present.
      Cardiovascular abnormalities are unfrequent in this syndrome (20% of the cases).
      They are dominated by ventricular septal defect and PDA. Hemodynamic failure and
      related growth retardation can lead to cardiac surgery.

PMID- 14666801
TI  - [Recent traumatic peroneal tendon dislocation: a case report].
AB  - Peroneal tendons dislocation describes a permanent or intermittent displacement
      of these tendons out of the retro malleolar sucket to its lateral side. It was
      described in fist in 1803 by Monteggia. It remains a rare affectation, dominantly
      of traumatic causes, mostly by passed in emergency situation. Also in its rarity,
      it remains remarkable for its diagnostic interest but also for its management
      which remains only surgical. This case concerned an adult of 24 years old, victim
      of closed trauma of the right ankle, the ankle was forced in varus and supine
      position. Ths initial diagnosis was a benign sprain which was later rectified 14
      days after for a diagnosis of peroneal tendons dislocation. During the operation,
      a rupture of the retinaculum like type II of Eckert and Davis was noticed. A
      simple suture technique using Exner method give a good result 14 months later.
      The authors insist after this case indifferential diagnosis with sprain and
      recommended a surgical repair in recent lesions.

PMID- 14666802
TI  - [Permanent cardiac stimulation in Senegal: preliminary experience at the
      Cardiology Clinic of Dakar].
AB  - We report a prospective and descriptive study in 12 patients who had pacemaker
      implantation from may. 1996 and dec. 1997. Our patients benefited from complete
      clinical examination, ECG (12 derivations), standard laboratory tests, chest X
      ray. Pulsed-Doppler, two dimensional and TM echocardiography have been performed.
      Stimulation was achieved using endocardial lead introduced percutaneously. During
      the study, 12 patients over 22, representing 55% of the subjects with symptomatic
      conduction defects, had definitive pacemaker implantation. Mean age was 53.8
      years +/- 18. Most of the patients lived in Dakar. Sex-ratio was 0.58 (7 males/5
      females). Most of the patients (83%) had low socio-economical status. Before
      implantation mean heart rate was 47 bpm +/- 20.8. Mean blood pressure was 155
      mmHg +/- 26.7 (systolic) and 71.6 +/- 20.8 mmHg (diastolic). Heart failure was
      present in 5 patients/12. Others symptoms were mainly syncope (83%). Mean
      cardiothoracic ratio was 0.56 +/- 0.09. Over a 14 months period we have implanted
      7 double chamber stimulators (DDD) and 5 monochamber (VVI). Over a 210 days
      follow-up, main problems are infection of the pocket in 2 patients. In one of
      them culture was positive. In Senegal, it is necessary to develop cardiac
      stimulation. Pacemakers should be available for all patients with symptomatic
      conduction defects. A national center for electrophysiologic studies and
      pacemaker implantation is a priority.

PMID- 14666803
TI  - The pyramid of plastic surgery today.

PMID- 14666804
TI  - Ultrasound-assisted lipoplasty.
AB  - The use of ultrasound-assisted lipoplasty (UAL) to assist in the removal of
      subcutaneous fat has been practiced in Europe for nearly 15 years and over the
      last 7 years has gained popularity in the United States. Liposuction is now one
      of the most commonly performed cosmetic procedures by board-certified plastic
      surgeons. This article will review the UAL procedure, its history, regulatory
      issues, instrumentation and equipment needed. It will also review changes and
      recent updates, clinical protocol, complications, and future considerations.

PMID- 14666805
TI  - Body contouring of the trunk/thigh aesthetic unit.
AB  - Modern body lifting is an exciting frontier for patients and the plastic surgery
      team. Aesthetic body contour deformities often involve multiple areas of the
      trunk and thighs. Surgery must take into account the effect on the overall
      aesthetic balance of the body. While the results can be dramatic and fulfilling,
      the surgeries are labor-intensive and challenging, and the recovery requires
      patient commitment and compliance.

PMID- 14666806
TI  - A review of breast contouring.
AB  - This article provides a comprehensive review of breast contouring and recent
      advances. Most of the material discussed covers both breast reduction and
      mastopexy, as well as reasons for breast contouring, advances in surgical
      techniques, results of breast contouring, nursing interventions, and insurance
      issues.

PMID- 14666807
TI  - The Internet as an educational tool for breast augmentation.
AB  - The new and rapidly expanding role of the Internet to inform and educate has
      provided the public with valuable information about medications, diagnosis,
      treatments, and surgeries. The purpose of this article is to share a brief
      explanation of how the nurse can play a role in patient education by interactive
      communication via the Internet.

PMID- 14666808
TI  - Body dysmorphic disorder: recognition and treatment.
AB  - Body dysmorphic disorder (BDD) is classified as a somatoform disorder in the
      Diagnostic and Statistical Manual of Mental Disorder-IV-TR (DSM-IV-TR) (American
      Psychiatric Association, 2000). According to the DSM-IV-R, BDD is characterized
      as a preoccupation with an imagined defect in appearance. If a slight physical
      anomaly exists, the person's concern is markedly excessive and this preoccupation
      causes clinically significant distress or impairment in social, occupational, or
      other important areas of functioning. This diagnosis is most appropriately used
      when symptoms associated with this dissatisfaction with the body shape and size
      are not better explained by an eating disorder (American Psychiatric Association,
      2000).

PMID- 14666809
TI  - Safe usage of lidocaine for liposuction.

PMID- 14666810
TI  - Successful photography of body contouring.

PMID- 14666811
TI  - Financial and speed collections.

PMID- 14666812
TI  - Office education: preparing for liposuction.

PMID- 14666813
TI  - Using the uniform in politics: where do we draw the line?

PMID- 14666814
TI  - Reducing the impact of stroke.

PMID- 14666815
TI  - It's real, basic nursing'.

PMID- 14666816
TI  - The cost of compromise.

PMID- 14666817
TI  - A consistent and reliable tool for malnutrition screening.
AB  - Malnutrition is both preventable and treatable and yet it continues to undermine
      the health of a significant proportion of the UK population. The Malnutrition
      Advisory Group (MAG) has launched a screening tool for use by all health
      professionals to screen patients with any disease or condition. The malnutrition
      universal screening tool (MUST) is endorsed by the British Dietetic Association,
      the RCN and the Registered Nursing Homes Association. These groups are now
      actively working with MAG to develop appropriate professional training
      opportunities.

PMID- 14666818
TI  - Ensuring that having a vasectomy is an informed decision.
AB  - Vasectomy or male sterilisation is the severing or electrocoagulation of the vas
      deferens connecting the testes to the seminal vesicles and urethra. It is a safe
      and a highly effective operation that offers a permanent method of contraception.
      Reversal of a vasectomy is possible but can be difficult and is not always
      successful. The permanency of the procedure means that careful counselling is
      essential and, where appropriate, should be conducted with both partners.

PMID- 14666819
TI  - What you need to know about ... paediatric constipation.

PMID- 14666820
TI  - Educating nursing staff involved in the provision of dementia care.
AB  - Evidence from several studies suggests that general nurses and acute health care
      staff do not always have an adequate understanding of the needs of people with
      dementia. This has major implications for the quality of care that is delivered
      and the well-being of people with dementia and a concurrent medical or surgical
      condition. This article describes how the creation of the role of nurse educator
      in dementia care helped to address this problem in one NHS trust.

PMID- 14666821
TI  - Acute pancreatitis: symptoms, diagnosis and management.
AB  - Pancreatitis is a relatively common condition that affects approximately one per
      cent of the population. Although the majority of attacks are mild, it is fatal in
      one in four people who develop it in a severe form. Clinical manifestations are
      so varied that the condition should be considered in the differential diagnosis
      of all upper abdominal pain until serum amylase concentrations become normal.
      Specific treatment is unavailable, therefore therapy is supportive, including the
      management of complications if and when they develop.

PMID- 14666822
TI  - The administration of drugs via enteral feeding tubes.
AB  - The practice of administering drugs via enteral feeding tubes has become complex.
      The range of enteral feeding tubes and medicines has increased dramatically in
      recent years and this has led to a gap between clinical practice and best
      practice.

PMID- 14666823
TI  - Usage of sip feeds in elderly care.
AB  - A study by Gosney (2003) aimed to identify the number of prescriptions and
      consumption of nutritional supplements (sip feeds) over a 24-hour period on an
      elderly care ward. This included the measurement and collection of anthropometric
      and biochemical data of patients who did and did not receive sip feeds in order
      to compare the indication for their use and calculate the cost of wasted feed.

PMID- 14666824
TI  - The provision of nutritional support for people with cancer.
AB  - Nutritional support is one of the most fundamental aspects of nursing practice.
      Evidence suggests that many patients are malnourished when admitted to hospital
      and this is a particular problem for patients with cancer (Whitman, 2000).

PMID- 14666825
TI  - Preventing health care-associated infections during enteral feeding.
AB  - IN the late 1980s, enteral feeding became common practice in hospitals for
      patients who were unable to feed themselves. It was therefore inevitable that
      those requiring long-term artificial feeding--that is, for more than 30 days-
      would continue this practice at home.

PMID- 14666826
TI  - How to ... manage your time effectively.

PMID- 14666827
TI  - Practice-based learning and improvement: an introduction.

PMID- 14666828
TI  - Practice-based learning and improvement: a dream that can become a reality.
AB  - Systematically enhancing learning from experience (practice-based learning)
      dominates the teachings of Sir William Osler and adult learning theorists such as
      Eduard Lindeman, Malcolm Knowles, and Cyril Houle. Because of time constraints,
      most physicians have not implemented methods that systematically facilitate
      learning from day-to-day work, but improvements in information technology offer
      the promise of making systematic practice-based learning practical. At least four
      ingredients need to be incorporated to significantly enhance learning from
      experience: a database that makes it possible to study individual practices;
      methods for supplying short, quick answers to questions while seeing patients; a
      reminder system to avoid errors of omission; and the opportunity to discuss
      practice data with colleagues. Great progress has been made, but significant
      barriers still must be overcome before a majority of physicians will participate.
      In particular, methods of data collection must be simplified, the delivery of
      point-of-care information and reminders must become more automatic, and
      physicians must develop skills to make the discussion of practice data
      acceptable, stimulating, and not unduly punitive.

PMID- 14666829
TI  - Place matters in physician practice and learning.
AB  - Since the early 1960s, most discussions about the improvement of continuing
      medical education (CME) have begun by seeking a better understanding of how
      physicians learn. The goal of this movement has been to put physician learners
      and their learning needs, not new research findings, at the center of the
      educational process. This has led CME away from the update model of education and
      into many innovative and exciting educational developments. However, as the
      conditions of medical practice have been changing in the past 20 years, the
      possibilities and conceptions of CME have also changed. Many in medicine and CME
      now recognize that the real world of physician decision making takes place in a
      highly charged political-economic context, where the interaction between the
      patient and physician is perhaps the least complex element. From this fundamental
      starting point, an emerging discourse has begun in CME that addresses physicians'
      changing work environments, the accountability schemes and financial incentives
      built into medical practice, and the importance of physicians' community of peers
      in making practice changes. We need to build on these observations to change the
      focus from "how physicians learn" to "where physicians learn." From this new
      perspective, physician practice and learning are seen as fundamentally social
      acts, and our attention is drawn to all of the ways in which "place matters."
      Attention to where physicians practice and learn can be used to improve CME.

PMID- 14666830
TI  - Stakeholder expectations in practice-based medicine.
AB  - Competitive pressures are forcing physicians from solo practice into new
      organizational structures. These new structures and the technologies supporting
      them have generated suggestions for improving medical practice. This article
      examines the unspoken assumption often accompanying these suggestions that
      practice improvement can come about through a closer alignment of the practice's
      goals and values with its stakeholders' expectations. Because conflict among
      competing goals is inevitable in a resource-scarce environment, an important
      question for each practice, and for each individual physician in a practice, is
      how to adjudicate conflicts of value when the goals of the practice appear to
      collide. This essay concludes with a proposal for an adjudicating process to help
      resolve these conflicts in practice-based medicine.

PMID- 14666831
TI  - Systems thinking: a new lens for old problems.
AB  - This article introduces systems thinking and identifies its implications for
      practice-based learning and improvement. The article defines systems, identifies
      fundamental aspects of systems thinking, and provides strategies for creating
      more practice-based learning environments in medical contexts.

PMID- 14666832
TI  - Teaching performance improvement: an opportunity for continuing medical
      education.
AB  - Practicing physicians generally are not engaged in either the methods of
      performance improvement for health care or the measurement and reporting of
      clinical outcomes. The principal reasons are lack of compensation for such work,
      the perception that the work of performance improvement adds no value and is a
      waste of time, the lack of knowledge and skill in the use of basic tools for
      outcomes measurement and performance improvement, the failure of medical
      educators to teach these skills, and the inability of mentors to model their use
      in practice. In this article, an overview of the history of quality improvement
      or performance improvement in general and the adoption of two methods of
      improvement (Plan-Do-Study-Act and SIX SIGMA) by health care is given. Six simple
      tools that are easy to understand and use and could be used in every continuing
      medical education (CME) program are then explained and illustrated. Postgraduate
      medical educators and CME program directors must step up to the challenge of
      teaching these skills. By learning to include them in planning, evaluation,
      policy making, and needs assessments of CME programs, the skills of every
      physician could be improved. Additional goals of every CME program could be
      accountability for outcomes, reduction of errors, alignment of incentives, and
      advocacy for the very best in evidence-based health care. To develop activities
      that affect physician practice and population health, CME professionals must
      partner with performance improvement experts for needs assessment and evaluation
      of outcomes data. An understanding of performance improvement principles helps
      those in performance improvement and those in CME to determine which educational
      activities might be expected to influence physician competency and performance.

PMID- 14666833
TI  - Information mastery: integrating continuing medical education with the
      information needs of clinicians.
AB  - Traditional continuing medical education (CME) has been disconnected from the
      actual practice of medicine and has not focused on providing the most useful
      information in the most efficient way. Physicians have different information
      needs at different times. When asked at the end of a day of patient care,
      physicians will typically report having had one question for every four or five
      patients. However, direct observation during patient care reveals many more
      questions. In the outpatient primary care setting, most studies have found, on
      average, that about two clinical questions are generated during every three
      patient encounters, with even higher numbers reported in the inpatient teaching
      setting. Thus, a physician seeing 25 patients in a typical day of outpatient care
      may have 15 clinical questions. Because clinical questions are the result of
      critical reflection by a clinician on his or her practice, they are central, to
      physician learning. This connection between "need" and learning is consistent
      with generally accepted theories of adult learning. When applied to continuing
      education, this connection suggests that physicians will learn best when learning
      is in the context of patient care, answers their questions, does not take too
      much time, and is directly applicable to their work. Pursuing answers to these
      questions and answering them with the best available evidence, at the time the
      answer is needed, may well change the physician's general approach to patient
      care.

PMID- 14666834
TI  - Physician leadership: influence on practice-based learning and improvement.
AB  - In response to the technology and information explosion, practice-based learning
      and improvement is emerging within the medical field to deliver systematic
      practice-linked improvements. However, its emergence has been inhibited by the
      slow acceptance of evidence-based medicine among physicians, who are reluctant to
      embrace proven high-performance leadership principles long established in other
      high-risk fields. This reluctance may be attributable to traditional medical
      training, which encourages controlling leadership styles that magnify the
      resistance common to all change efforts. To overcome this resistance, physicians
      must develop the same leadership skills that have proven to be critical to
      success in other service and high-performance industries. Skills such as self
      awareness, shared authority, conflict resolution, and nonpunitive critique can
      emerge in practice only if they are taught. A dramatic shift away from control
      and blame has become a requirement for achieving success in other industries
      based on complex group process. This approach is so mainstream that the burden of
      proof that cooperative leadership is not a requirement for medical improvement
      falls to those institutions perpetuating the outmoded paradigm of the past.
      Cooperative leadership skills that have proven central to implementing change in
      the information era are suggested as a core cultural support for practice-based
      learning and improvement. Complex adaptive systems theory, long used as a way to
      understand evolutionary biology, and more recently computer science and
      economics, predicts that behavior emerging among some groups of providers will be
      selected for duplication by the competitive environment. A curriculum framework
      needed to teach leadership skills to expand the influence of practice-based
      learning and improvement is offered as a guide to accelerate change.

PMID- 14666835
TI  - Practice-based learning and improvement.
AB  - Workplace learning is becoming increasingly important in all fields. While
      workplace learning in medicine, also called practice-based learning and
      improvement (PBLI) is not new, understanding how it works and how it fits with an
      individual physician's continuing professional development is new. In this
      article, we describe seven issues associated with PBLI and then pose questions
      for reflections, as continuing medical education (CME) planners consider working
      with PBLI.

PMID- 14666836
TI  - New Jersey experiment. Eight hospitals will participate in CMS 'gainsharing'
      project, in which doctors can earn bonuses of up to 25% on Medicare fees.
AB  - A CMS project will let doctors earn bonuses for helping hospitals cut inpatient
      costs, using software designed by Michael Kalison, left. But not everyone is
      excited about the plan, including U.S. Rep. Pete Stark, the California Democrat
      who championed the physician self-referral legislation the CMS is waiving for the
      program.

PMID- 14666837
TI  - After the storm. Medicare bill foes vow to overturn provisions.

PMID- 14666838
TI  - Rating adjustment. Moody's ponders corporate rules for not-for-profits.

PMID- 14666839
TI  - Weapon of debt reconstruction. Ohio hospital hopes to stay open after filing
      second Chapter 11.

PMID- 14666840
TI  - The architecture of reform. How design of imaging facilities can be template for
      a new health system.

PMID- 14666841
TI  - Grudge match. With a new CT heart scan gaining acclaim, radiologists and
      cardiologists are ready to go to the mat again in battle over control of the
      procedure.

PMID- 14666842
TI  - Acting the part. As HHS' interim IG, Corrigan says she's able to use every skill
      she's ever developed in her leading role.

PMID- 14666843
TI  - Sleep--is the 24/7 lifestyle leaving us seriously short?

PMID- 14666844
TI  - Will the UK's sexual health strategy work?

PMID- 14666845
TI  - Continuing to breast feed: how health professionals can help mothers.
AB  - A National Breast Feeding Adviser from the Department of Health discusses current
      breast-feeding rates and the UK's new infant feeding policy which recommends
      exclusive breast feeding for the first six months of the infant's life. The
      author outlines the main reasons why many mothers give up breast feeding sooner
      than this. She provides several practical tips for health professionals on
      providing positive encouragement, education and advice for mothers to help them
      continue. These are targeted at some of the key stages at which mothers are
      likely to abandon breast feeding.

PMID- 14666846
TI  - The new "breast from birth" growth charts. An updated version of the paper given
      at the Primary Care Conference and Exhibition, May 2003.
AB  - The Child Growth Foundation has published the first weight reference charts
      specifically designed for the breast-fed infant. Based on a sample of 120 long
      term British breast-fed babies, the charts demonstrate the particular growth
      pattern of breast-fed babies. This differs from formula-fed infants in that
      breast-fed babies initially gain weight more rapidly, but from two to three
      months of age their weight gain decreases and they begin to move downwards across
      centiles. At present breast-fed babies are measured against the standard British
      1990 weight reference chart rather than one that reflects the pattern of the long
      term breast-fed baby. The author, Tam Fry from the Child Growth Foundation,
      argues that the new charts will prevent mothers and health professionals from
      becoming anxious and changing the infant from breast to formula milk when growth
      begins to slow down. He also suggests that the charts could be used as the
      reference for all British babies, whatever the means of feeding.

PMID- 14666847
TI  - Health and fitness series--5. Managing anorexia nervosa and other eating
      disorders.
AB  - At a time when obesity is a major public health concern, society paradoxically
      prefers thinness. This, along with the increase in dieting seen over recent
      years, has inevitably been linked to a rise in the incidence of eating disorders.
      This article describes the features and complications of eating disorders and
      gives advice on how these disorders can be identified and managed.

PMID- 14666848
TI  - Egg and sperm donation: an issue for health care professionals?
AB  - The author, who is Chair of the National Gamete Donation Trust, outlines the
      problem of individuals for whom the only hope of having a child of their own is
      through infertility treatment using donated eggs or sperm (gamtete donation).
      Although there are licensed centres where this treatment is available, there is a
      serious shortage of donor eggs for infertile women. The National Fertility and
      Embryo Authority has ruled against payment for donor eggs but women who have
      given eggs report satisfaction at having been able to help others, despite the
      discomfort and inconvenience. The author stresses the need to raise awareness of
      gamete donation among the public and health professionals and lists agencies
      providing further information.

PMID- 14666849
TI  - [The Specialist Prize in Nursing Sciences].

PMID- 14666850
TI  - [In memory of Annamaria de Feo].

PMID- 14666851
TI  - [Survey on quality of life of patients undergoing dialytic treatment].
AB  - The Nottingham Health Profile (NHP) was administered to 85 dialysis patients
      treated at Mestre Hospital, to assess their quality of life and compare any
      differences between haemodialysis (HD) and peritoneal dialysis (PD) patients. The
      two groups were similar for the main characteristics. Overall dialysis patients
      do not enjoy a good quality of life. Comparing baseline demographic and clinical
      scores, 72.9% patients have problems with energy and 69.4 with mobility, 47.1%
      refer pain and 54.1% sleep disorders. The main differences between HD and PD
      patients concern psychological reactions, where 42.9% of HD patients report "at
      risk/compromised" scores compared to 17.2% of PD patients. NHP showed to be an
      easy to administer and efficient instrument in identifying areas of concern for
      dialysis patients.

PMID- 14666852
TI  - [Quality of life in patients with unusual diseases: experience of nurses at the
      clinical research center for unusual diseases Aldo e Cele Dacco].
AB  - The Information Centre for Rare Diseases (CIMR) of the Mario Negri Institute, has
      promoted a specific study on quality of life of patients with Takayasu's
      arteritis, a chronic vasculitis with unclear etiology, that affects primarily
      aorta and its main branches. The aim of the study is to assess the QoL of Italian
      Takayasu's arteritis patients referring to the CIMR, using the SF-36 Health
      Survey. The SF-36 questionnaire was submitted to 61 Takayasu arteritis patients
      who covered the inclusion criteria of the study, with a response rate of 85.25%,
      (6 males and 46 females). Expectedly, the overall SF-36 scores of the study
      population were lower compared to the general Italian population specifically
      with respect to General Health and Vitality scales. More extensive research would
      be required to explore gender differences suggested by the study.

PMID- 14666853
TI  - [Ergonomic analysis of nursing activities in relation to the development of
      musculoskeletal disorders].
AB  - Musculoskeletal disorders are frequent among nurses. The literature so far
      focused mainly on back pain while paying little attention to disorders of the
      upper and lower limbs. Back pain is associated to patients' handling, but we know
      very little on the effect of awkward postures due to frequent bending and
      twisting and of work organisation which could also be involved in the genesis of
      these disorders. The pain localised to the musculoskeletal apparatus, including
      the presence of multiple complaints, was studied in a group of 70 nurses, with
      Estev and Vistat questionnaires, together with the possible association to work
      conditions. An ergonomic analysis of nursing activities (the postures and
      cognitive workload) was carried out to uncover associations to the risk of
      developing musculoskeletal disorders. Results show an involvement of all
      musculoskeletal sites and a high prevalence of multiple pain complaints (54% of
      the nurses). Ergonomic analysis highlighted the adoption of awkward postures for
      prolonged times. Moreover, nurses are frequently interrupted and their working
      pace is under continuous time pressure. Cognitive workload and work organisation
      should also be addressed, besides the postures, as factors which could compromise
      the health of nurses and influence the quality of care.

PMID- 14666854
TI  - [Reception of the ASL 3 "Genovese": the point of view of the citizens and
      operators].
AB  - The quality of the reception of the patients in the health services is one of the
      projects of one of the Local Health Authorities of Genova, with the aim of
      improving its personalization, information and humanization and, therefore, its
      perceived quality. The judgements of patients and health workers were collected.
      Ten focus groups with 146 patients representing different populations (mothers,
      elderly, people living in suburbs) were activated, and 2644 questionnaires were
      distributed to the health workers (nurses, technicians, clerks etc) of the
      hospitals and districts (response rate 62%). Efficiency is the key meaning of
      reception for health care workers (giving information, orienting receiving with
      politeness and kindness); whilst patients value more other aspects such as the
      interpersonal relationship and the humanization (empathy, listening, answer to
      needs). Both stress the need of easing procedures and clinical pathways. Patients
      and health care workers judge physical environments (rooms, furnitures, signs,
      bathrooms) inadequate and for patients this judgement is more negative for the
      hospital compared to the district. Scarcity of readily accessible personnel and a
      non-individual centered approach are the two main specific complaints, while a
      general observation of dissatisfaction is attributed to the fact that everything
      seems to be left to the good will of individual health care workers. The data
      collected are now used to plan educational initiatives, protocols more broadly to
      redefine procedures of reception. Because of their role and number nurses may
      certainly play a pivotal role in this process.

PMID- 14666855
TI  - [Research on quality and quality of research: for a critical reflection on
      methods of qualitative research].

PMID- 14666856
TI  - [Pharmacological surveillance centered on the patient: problem-based
      bibliographic guide].

PMID- 14666857
TI  - [Drug plundering].

PMID- 14666858
TI  - Rebuilding an empire. Once a crown jewel of healthcare in the Middle East, Iraq's
      system needs a complete overhaul, everything from equipment to staff.
AB  - As work begins to rebuild Iraq's infrastructure, hospitals and primary-care
      facilities are major priorities. While security concerns have prevented some U.S.
      civilians from traveling there to lend their assistance, hospital executives soon
      could participate in exchange programs to educate their Iraqi counterparts. James
      Haveman, left, is senior U.S. adviser to the Iraqi Ministry of Health.

PMID- 14666859
TI  - Extracting payment. Hospitals try collecting before patients leave ER.

PMID- 14666860
TI  - Partnerships get scrutiny.

PMID- 14666861
TI  - AHA links with 'U.S. News'. Hospital directory to be separate from rankings.

PMID- 14666862
TI  - Rising by degrees. Management titles, diplomas lead to higher salaries for
      physicians, survey shows.

PMID- 14666863
TI  - Storm warning. 'Rainmaker' doctors bring in big bucks for hospitals, but when
      oversight goes awry, they also can bring a deluge of legal problems.

PMID- 14666864
TI  - By the numbers. Top healthcare bond counsel firms.

PMID- 14666865
TI  - Nebulizer coding made easy.

PMID- 14666866
TI  - Practice expenses.

PMID- 14666867
TI  - Sick relatives? Get involved!

PMID- 14666868
TI  - Create a first-rate first impression.

PMID- 14666869
TI  - Why I go back to Vietnam.

PMID- 14666870
TI  - The world according to HIPAA.

PMID- 14666871
TI  - Do you know enough about your parents' finances?

PMID- 14666872
TI  - I'm a doctor ... and I played one on TV.

PMID- 14666873
TI  - "I didn't know I was suing you!".

PMID- 14666874
TI  - If patients question your Rx.

PMID- 14666875
TI  - When an insurer won't cover your best advice.

PMID- 14666876
TI  - Legislative update.

PMID- 14666877
TI  - Tax exempt status and articles of incorporation.

PMID- 14666878
TI  - Breast cancer and SIDS awareness.

PMID- 14666879
TI  - ANA launches back injury prevention campaign handle with care.

PMID- 14666880
TI  - 12 tips on writing for nursing journals.

PMID- 14666881
TI  - My journey into nursing.

PMID- 14666882
TI  - Angels among us.

PMID- 14666883
TI  - A vision from research to practice.

PMID- 14666884
TI  - Lower-cost defibrillator.

PMID- 14666885
TI  - Preventing monkeypox.

PMID- 14666886
TI  - AstraZeneca to pay $355 million fine.

PMID- 14666887
TI  - Concerns about Paxil for children.

PMID- 14666888
TI  - Deceptive marketing practices for dietary supplements halted.

PMID- 14666889
TI  - First once-daily protease inhibitor.

PMID- 14666890
TI  - First biologic for allergy-related asthma.

PMID- 14666891
TI  - Combination diabetes device.

PMID- 14666893
TI  - FDA announces initiative to curb counterfeit drugs.

PMID- 14666892
TI  - Barr Laboratories recalls Nortrel contraceptive.

PMID- 14666894
TI  - New test predicts heart risk.

PMID- 14666895
TI  - Consumer guide for malaria drug.

PMID- 14666896
TI  - FDA approves new drug for treatment of erectile dysfunction in men.

PMID- 14666897
TI  - Severe childhood ADHD may predict alcohol, substance use in teen years.

PMID- 14666899
TI  - MedWatch: managing risks at the FDA.

PMID- 14666898
TI  - HHS, FDA implement Food Security Research Program.
AB  - A new $5 million research program will help the Food and Drug Administration
      develop technologies and strategies to minimize potential threats to the safety
      and security of the nation's food supply.

PMID- 14666900
TI  - Greater access to generic drugs. New FDA initiatives to improve drug reviews and
      reduce legal loopholes.

PMID- 14666901
TI  - First test approved to help detect West Nile virus.

PMID- 14666902
TI  - Revealing trans fats.

PMID- 14666903
TI  - Nasal flu vaccine approved.

PMID- 14666904
TI  - Former FDA press officer looks back at 100.

PMID- 14666905
TI  - Inside clinical trials: testing medical products in people.

PMID- 14666906
TI  - Daily aspirin therapy.

PMID- 14666907
TI  - Idaho woman sentenced for touting bogus medical cure.

PMID- 14666908
TI  - Trans fatty acids: better decisions or information overload?

PMID- 14666909
TI  - Lexiva (fosamprenavir) approved.
AB  - The FDA approved a prodrug that becomes amprenavir in the body, but has practical
      advantages over amprenavir.

PMID- 14666910
TI  - Warning against tenofovir + ddI + 3TC, and "triple nuke" combinations.
AB  - Another regimen consisting only of nucleoside-analog drugs has shown
      unsatisfactory suppression of HIV.

PMID- 14666911
TI  - Clinton Foundation gets big price reduction--to 40 cents a day for three-drug
      combination.
AB  - The price of triple-combination antiretroviral treatment in poor countries can
      now be less than 40 cents a day.

PMID- 14666912
TI  - Returning to work after disability; what you should know. Interview by John S.
      James.
AB  - A leader in the movement to help people consider returning to work after
      disability looks at some of the medical, financial/legal, vocational, and
      psychosocial issues involved--and how to get help with them (interview, part 1 of
      2).

PMID- 14666913
TI  - Meeting notes from the 2nd International AIDS Society Conference on HIV
      Pathogenesis and Treatment. T-20 salvage results hold up at 48 weeks.
AB  - In a combined analysis from TORO-1 and TORO-2, T-20 remains effective as "deep
      salvage" out to 48 weeks.

PMID- 14666914
TI  - Meeting notes from the 2nd International AIDS Society Conference on HIV
      Pathogenesis and Treatment. Atazanavir in treatment-experienced patients.
AB  - Two industry-sponsored prospective studies provide some clarification regarding
      the optimal use of the new PI atazanavir in PI-experienced patients.

PMID- 14666915
TI  - The evolution of community outreach at ASP.

PMID- 14666916
TI  - The CDC's 2003 National HIV Prevention Conference.

PMID- 14666917
TI  - Leadership training program: where do we go from here?

PMID- 14666918
TI  - HIPAA: understanding your rights of insurance portability and privacy.

PMID- 14666919
TI  - New treatment available for AIDS cachexia.

PMID- 14666920
TI  - News from the 2nd IAS Conference on HIV Pathogenesis and Treatment.

PMID- 14666921
TI  - NRTI-related mitochondrial toxicity in an HIV-infected woman.

PMID- 14666922
TI  - Risk, HIV and STD prevention.

PMID- 14666923
TI  - An overview of sexually transmitted disease.

PMID- 14666924
TI  - Nanofabrication for micropatterned cell arrays by combining electron beam
      irradiated polymer grafting and localized laser ablation.
AB  - Most methods reported for cell-surface patterning are generally based on
      photolithography and use of silicon or glass substrates with processing analogous
      to semiconductor manufacturing. Herein, we report a novel method to prepare
      patterned plastic surfaces to achieve cell arrays by combining homogeneous
      polymer grafting by electron beam irradiation and localized laser ablation of the
      grafted polymer. Poly(N-isopropylacrylamide) (PIPAAm) was covalently grafted to
      surfaces of tissue culture-grade polystyrene dishes. Subsequent ultraviolet ArF
      excimer laser exposure to limited square areas (sides of 30 or 50 microm)
      produced patterned ablative photodecomposition of only the surface region
      (approximately 100-nm depth). Three-dimensional surface profiles showed that
      these ablated surfaces were as smooth and flat as the original tissue culture
      grade polystyrene surfaces. Time-of-flight secondary ion mass spectrometry
      analysis revealed that the ablated domains exposed basal polystyrene and were
      surrounded with PIPAAm-grafted chemistry. Before cell seeding, fibronectin was
      adsorbed selectively onto ablated domains at 20 degrees C, a condition in which
      the non-ablated grafted PIPAAm matrix remains highly hydrated. Hepatocytes seeded
      specifically adhered onto the ablated domains adsorbed with fibronectin. Because
      PIPAAm, inhibits cell adhesion and migration even at 37 degrees C when the
      grafted density is > 3 microg/cm2, all the cells were confined within the ablated
      domains. A 100-cell domain array was achieved by this method. This surface
      modification technique can be utilized for fabrication of cell-based biosensors
      as well as tissue-engineered constructs.

PMID- 14666925
TI  - Use of vascular endothelial cell growth factor gene transfer to enhance
      implantable sensor function in vivo.
AB  - In the current study, we developed and validated a simple, rapid and safe in vivo
      model to test gene transfer and sensor function in vivo. Using the model, we
      tested the specific hypothesis that in vivo gene transfer of angiogenic factors
      at sites of biosensor implantation would induce neovascularization surrounding
      the sensor and thereby enhance biosensor function in vivo. As the in vivo site
      for testing of our gene transfer cell and biosensor function systems, the
      developing chorioallantoic membrane (CAM) of the embryo was utilized. Vascular
      endothelial cell growth factor (VEGF) was used as a prototype for angiogenic
      factor gene transfer. A helper-independent retroviral vector derived from Rous
      sarcoma virus (RSV), designated RCAS, was used for gene transfer of the murine
      VEGF (mVEGF) gene (mVEGF:RCAS) into the DF-1 chicken cell line (designated
      mVEGF:DF-1). Initially, the ability of VEGF:DF-1 cells to produce VEGF and RCAS
      viral vectors containing the mVEGF gene (mVEGF:RCAS) was validated in vitro and
      in vivo, as was the ability of the mVEGF:DF-1 cells to induce neovascularization
      in the ex ova CAM model. Using the system, we determined the ability of mVEGF:DF
      1 cells to enhance acetaminophen sensor function in vivo, by inducing
      neovascularization at sites of sensor implantation in the ex ova CAM model. For
      these studies, acetaminophen sensors were placed on 8-day-old ex ova CAMs,
      followed by addition of media or cells (mVEGF:DF-1 cells or GFP:DF-1 cells) at
      the sites of biosensor implantation on the CAM. At 4 to 10 days after sensor
      placement, the biosensor function was determined by measuring sensor response to
      an intravenous injection of acetaminophen. Sensors implanted on CAMs with buffer
      or control cells (GFP:DF-1 cells) displayed no induced neovascularization around
      the sensor and had minimal/baseline sensor responses to intravenous acetaminophen
      injection (media, 133.33 +/- 27.64 nA; GFP:DF-1, 187.50 +/- 55.43 nA).
      Alternatively, the sensors implanted with mVEGF:DF-1 cells displayed massive
      neovascularization and equally massive sensor response to intravenous injection
      of acetaminophen (VEGF:DF-1, 1387.50 +/- 276.42 nA). These data clearly
      demonstrate that enhancing vessel density (i.e., neovascularization) around an
      implanted sensor dramatically enhances sensor function in vivo.

PMID- 14666926
TI  - Jordanian population data on five STR forensic loci: D16S539, TPOX, CSF1PO, Penta
      D, and Penta E.
AB  - The allele distributions at five STR loci, D16S539, TPOX, CSF1PO, Penta D, and
      Penta E have been determined. None of the five loci were found to deviate from
      Hardy-Weinberg expectations according to the results of the G (homogeneity) test.

PMID- 14666927
TI  - The evolution of Eisenmenger's eponymic enshrinement.

PMID- 14666928
TI  - Chronic myelomonocytic leukemia.

PMID- 14666929
TI  - Spinal manipulative therapy is an independent risk factor for vertebral artery
      dissection.

PMID- 14666930
TI  - Spinal manipulative therapy is an independent risk factor for vertebral artery
      dissection.

PMID- 14666931
TI  - Practice parameter: evaluation of the child with global developmental delay.

PMID- 14666937
TI  - Etiology of maxillary necrosis.

PMID- 14666938
TI  - Exogenous bone morphogenetic protein may improve distraction osteogenesis
      outcomes.

PMID- 14666939
TI  - Benefits of the brush biopsy.

PMID- 14666940
TI  - Ageism in trauma call?

PMID- 14666941
TI  - cAMP-independent relaxation of smooth muscle cells via Gs-coupled receptors.

PMID- 14666942
TI  - Support of prompt adoption of ICD-10-CM and ICD-10-PCS medical code set standards
      in the United States.

PMID- 14666943
TI  - Muscle fiber characteristics and performance correlates of male Olympic-style
      weightlifters.
AB  - Biopsies fro the vastus lateralis muscle of male weightlifters (WL; n=6; X +/-
      SE, age=27.0 +/- 2.1 years), and non-weight-trained men (CON; n=7; age=27.0 +/-
      2.0 years) were compared for fiber types, myosin heavy chain (MHC) and titin
      content, and fiber type-specific capillary density. Differences (p<0.05) were
      observed for percent fiber types IIC (WL=0.4 +/- 0.2, CON=2.4 +/- 0.8); IIA
      (WL=50.5 +/- 3.2, CON=26.9 +/- 3.7); and IIB (WL=1.7 +/- 1.4, CON=21.0 +/- 5.3),
      as well as percent MHC IIa (WL=65.3 +/- 2.4, CON=52.1 +/- 4.2) and percent MHC
      IIB (WL=0.9 +/- 0.9; CON=18.2 +/- 6.1). All WL exhibited only the titin-1
      isoform. Capillary density (caps.mm(-2)) for all fiber types combined was greater
      for the CON subjects (WL=192.7 +/- 17.3; CON=262.9 +/- 26.3), due primarily to a
      greater capillary density in the IIA fibers. Weightlifting performances and
      vertical jump power were correlated with type II fiber characteristics. These
      results suggest that successful weightlifting performance is not dependent on IIB
      fibers, and that weightlifters exhibit large percentages of type IIA muscle
      fibers and MHC IIa isoform content.

PMID- 14666944
TI  - Effects of short-term training using powercranks on cardiovascular fitness and
      cycling efficiency.
AB  - Powercranks use a specially designed clutch to promote independent pedal work by
      each leg during cycling. We examined the effects of 6 wk of training on cyclists
      using Powercranks (n=6) or normal cranks (n=6) on maximal oxygen consumption
      (VO2max) and anaerobic threshold (AT) during a graded exercise test (GXT), and
      heart rate (HR), oxygen consumption (VO2), respiratory exchange ration (RER), and
      gross efficiency (GE) during a 1-hour submaximal ride at a constant load.
      Subjects trained at 70% of VO2max for 1 h.d(-1), 3 d.wk(-1), for 6 weeks. The GXT
      and 1-hour submaximal ride were performed using normal cranks pretraining and
      posttraining. The 1-hour submaximal ride was performed at an intensity equal to
      approximately 69% of pretraining VO2max with VO2, RER, GE, and HR determined at
      15-minute intervals during the ride. No differences were observed between or
      within groups for VO2max or AT during the GXT. The Powercranks group had
      significantly higher GE values than the normal cranks group (23.6 +/- 1.3% versus
      21.3 +/- 1.7%, and 23.9 +/- 1.4% versus 21.0 +/- 1.9% at 45 and 60 min,
      respectively), and significantly lower HR at 30, 45, and 60 minutes and VO2 at 45
      and 60 minutes during the 1-hour submaximal ride posttraining. It appears that 6
      weeks of training with Powercranks induced physiological adaptations that reduced
      energy expenditure during a 1-hour submaximal ride.

PMID- 14666945
TI  - Effects of vitamin E and C supplementation either alone or in combination on
      exercise-induced lipid peroxidation in trained cyclists.
AB  - Seven trained male cyclists (ate 22.3 +/- 2 years) participated in 4 separate
      supplementation phases. They ingested 2 capsules per day containing the following
      treatments: placebo (placebo plus placebo); vitamin C (1 g per day vitamin C plus
      placebo); vitamin C and E (1 g per day vitamin C plus 200 IU per kg vitamin E);
      and vitamin E (400 IU per kg vitamin E plus placebo). The treatment order
      (placebo, vitamin C, vitamin C and E, and vitamin E) was the same for all
      subjects. Performance trials consisting of a 60-minute steady state ride (SSR)
      and a 30-minute performance ride (PR) on Cybex 100 Metabolic cycles were
      performed after each trial. Workloads of 70% of the VO2max were set for the SSR
      and PR rides, with pedal rate maintained at 90 rpm (SSR) or self determined (PR).
      Blood samples (5 ml) were drawn pre- and postexercise and analyzed for
      malonaldehyde (MDA) and lactic acid. The results indicate that vitamin E
      treatment was more effective than vitamin C alone or vitamin C and E. Pre
      exercise plasma levels of MDA in the vitamin E trial was 39% below the pre
      exercise MDA levels of the placebo: 2.94 +/- 0.54 and 4.81 +/- 0.65 micromol per
      ml, respectively. Plasma MDA following exercise in the vitamin E group was also
      lower than teh placebo: 4.32 +/- 0.37 vs 7.89 +/- 1.0 micromol per ml,
      respectively. Vitamin C supplementation, on the other hand, elevated both the
      resting and exercise plasma levels of MDA. None of th supplemental phases had any
      significant effect on performance. In conclusion, the results indicate that 400
      IU/day of vitamin E reduces membrane damage more effectively than vitamin C but
      does not enhance performance. Athletes are encouraged to include antioxidants,
      such as vitamin E and C, in their diet to counteract these detrimental effects of
      exercise. The data presented here suggests that 400 IU/day of vitamin E will
      provide adequate protection but supplementing the diet with 1 g per day of
      vitamin C may promote cellular damage. However neither of these vitamins, either
      alone or in combination, will enhance exercise performance.

PMID- 14666946
TI  - Tooth key.

PMID- 14666947
TI  - [Study of the fibrinolytic, anti-coagulative, thrombolytic and hemorheologic
      action of Lumbricus].

PMID- 14666948
TI  - [Advances in the study on chemical constituents and pharmacology of Gelsemium
      elegans (Gardn. et Champ.) Benth].

PMID- 14666949
TI  - [Advances in the study of Cantharidin and its derivatives].

PMID- 14666950
TI  - Relationship between plaque morphology of carotid artery and aortic valve
      calcification.
AB  - Aortic and mitral valvular calcifications are found to be associated with
      atherosclerotic risk factors and are largely accepted as part of a generalized
      atherosclerotic process. As well as the severity of stenosis, embologenic
      properties of plaques are also responsible for ischemic potentials of
      atherosclerotic plaques in carotid arteries. In this study, the authors aimed to
      define the characteristics of plaque morphology in patients with and without
      aortic valvular calcification (AVC) and to show the association between AVC and
      carotid plaque characteristics. Carotid plaque morphology in 182 consecutive
      patients with AVC was compared with plaque characteristics in 170 patients
      without AVC. Risk factors for atherosclerosis, age, and gender were similar in
      patients with and without AVC. The presence of carotid atherosclerosis, complex
      atheromas, and carotid artery stenosis was significantly higher in patients with
      AVC when compared with those without AVC (p < 0.001, p < 0.001, and p < 0.05,
      respectively). Unstable plaques (Types I and II) were also found to be more
      common in the patients with AVC than in those without AVC (p < 0.001). This study
      demonstrated the strong correlation between AVC and carotid atheromas. The
      plaques in patients with AVC are more unstable in morphology than in those
      without AVC, and this may explain the higher stroke incidence in these patients.

PMID- 14666951
TI  - Prediction of short-term progression or regression of atherosclerotic coronary
      artery disease by lipoprotein (a): a quantitative coronary angiographic study.
AB  - This study assessed whether progression of coronary artery atherosclerotic
      lesions could be predicted in the short term using various lipid profiles. In 37
      patients (61.9 +/- 9.5 years) undergoing coronary angioplasty and with 6-month
      follow-up angiography, quantitative coronary angiography of a new or changed
      lesion was performed in the follow-up examination, except for intervention
      vessels. The progression-regression score of the assessed lesion was calculated
      as the baseline minus the follow-up minimal lumen diameter. The serum lipoprotein
      (a) level was higher in the progression group (progression-regression score >
      0.15 mm), than in the regression group (< or = -0.15 mm; p < 0.01) and the no
      change group (within +/- 0.15 mm; p < 0.05). Remnant-like lipoprotein particle
      cholesterol and apolipoprotein-B levels were also higher in the progression
      group. However, multiple regression analysis of the progression showed that the
      progression-regression score was independently correlated with lipoprotein (a)
      alone (R = 0.50, p < 0.05). This shows that lipoprotein (a) is an independent
      predictor of coronary atherosclerotic lesion progression over the short term.

PMID- 14666952
TI  - Stroke rate of off-pump coronary artery bypass; aortocoronary bypass versus in
      situ bypass.
AB  - Off-pump coronary artery bypass (OPCAB) using in-situ grafts does not require
      aortic manipulation, and it is theoretically free from the risk of stroke.
      Because of the limited availability of in-situ grafts, aortocoronary bypass has
      been conducted in addition to in-situ grafting. In this paper, the authors
      prospectively investigated whether or not on aortocoronary bypass increases the
      incidence of stroke after off-pump bypass. Perioperative data were collected
      prospectively from patients who underwent isolated off-pump bypass at their
      hospital group between March 1997 and February 2002. The patients were divided
      into 2 groups; group AC (patients with at least 1 aortocoronary bypass, n = 280)
      and group IS (patients with all in-situ grafts, n = 234). Patients with 3-vessel
      disease more frequently underwent aortocoronary bypass and patients with a
      history of stroke, calcified ascending aorta, or renal failure more often
      underwent in-situ graft. The number of distal anastomoses was greater in group AC
      (3.5 +/- 1.0) than in group IS (2.7 +/- 1.1), p < 0.0001. Patient recovery and
      complication rates were similar, including the occurrence of postoperative
      stroke: 3.0% (7/234) in group IS vs 0.7% (2/280) in group AC, p = 0.051, NS. The
      graft patency and remote results were not significantly different between the 2
      groups. Side clamping of the aorta used in off-pump aortocoronary bypass does not
      increase the risk of postoperative strokes compared to in-situ bypass.
      Postoperative stroke after OPCAB may depend on the patient's preoperative
      comorbidities.

PMID- 14666953
TI  - Comparison of changes in diastolic functions after aortic valve replacement with
      freestyle stentless porcine xenografts in patients with restrictive and
      nonrestrictive physiology.
AB  - In this study, the effect of valve replacement on diastolic parameters was
      evaluated preoperatively and postoperatively at 3, 6, and 12 months by comparing
      diastolic parameters in patients after aortic valve replacement with freestyle
      stentless porcine xenografts for aortic stenosis. Depending on deceleration time
      (DT) and isovolumetric relaxation time (IVRT) with preoperative echocardiographic
      assessment, patients were divided into two groups: restrictive physiology (DT <
      or = 150 msec and IVRT < 100 msec, 20 patients), and nonrestrictive physiology
      (DT > 150 msec and IVRT > or = 100 msec, 27 patients). Although left ventricular
      mass index significantly decreased in both groups, improvement in DT, IVRT, and
      ejection fraction occurred only in patients with restrictive physiology. As a
      result, the patients with restrictive diastolic characteristics had more benefit
      than the patients with nonrestrictive physiology after aortic valve replacement.

PMID- 14666954
TI  - Left ventricular mass in dippers and nondippers with newly diagnosed
      hypertension.
AB  - Hypertensive subjects can be subdivided into 2 groups, dippers and nondippers,
      according to the presence or the lack of a nocturnal fall of blood pressure of
      more than 10%. Several studies have investigated cardiac organ damage in the 2
      groups with discordant results, but they included subjects with different onset,
      severity, and treatment of hypertension. The authors selected 23 dippers and 17
      nondippers affected by newly (< 1 year) diagnosed grades 1 and 2 hypertension,
      never treated, who underwent 24-hour ambulatory blood pressure monitoring and M
      mode echocardiography. They did not find significant differences between the 2
      groups as regards the echocardiographic left ventricular and atrial dimensions or
      regarding the left ventricular mass, left ventricular mass index, or relative
      wall thickness. Also no significant differences were found in the rate of either
      left ventricular remodeling or left ventricular hypertrophy. These data suggest
      that nondipping status is not associated with a higher level of cardiac
      involvement in the early phases of hypertension compared to dipping status.

PMID- 14666955
TI  - The degree of albuminuria is related to left ventricular hypertrophy in
      hypertensive diabetics and is associated with abnormal left ventricular filling:
      a pilot study.
AB  - The association of albuminuria and left ventricular (LV) hypertrophy (LVH) in
      diabetics aggravates the prognosis. The authors studied the relation between LVH
      and the degree of albuminuria in diabetics and investigated the relationship of
      albuminuria to LV filling. A comparison was made between 30 hypertensive
      diabetics, 10 of whom had microalbuminuria (MIC) and 20 had macroalbuminuria
      (MAC), and 18 diabetics who were normotensive and normalbuminuric (NOR). LV mass
      index (LVMI) and LV ejection fraction (LVEF) were measured during
      echocardiography. LV filling pattern at rest and at peak standardized isometric
      exercise (IME) using handgrip was assessed by measuring E/A (peak velocity of the
      early/atrial filling waves) of the transmitral flow during Doppler and
      echocardiography. Each patient underwent a stress ECG test. LVMI was higher in
      MAC (132.3 +/- 55.4) than in MIC (115.6 +/- 32.5) or NOR (90.0 +/- 31.8)
      (p<0.01). There were more patients in MAC with LVH (n = 13) and abnormal filling
      (n = 9 at rest and 16 with IME) than in MIC (LVH = 5, abnormal filling = 1 at
      rest and 10 during IME) or NOR (LVH = 3, abnormal filling = 1 at rest and 9
      during IME) (p < 0.02). LVMI was not related to LVEF. Although blood pressure was
      not different between MAC and MIC groups, it was significantly higher than in the
      NOR group. This study suggests that a high degree of albuminuria in hypertensive
      diabetics is associated with greater value for LVMI and an increased incidence of
      LVH independent of blood pressure level or systolic LV function. LVH is
      associated with abnormal LV filling. The degree of albuminuria may predict LVMI
      and LVH, which are associated with abnormal LV filling. This association of
      abnormal LV filling with albuminuria in hypertensive diabetic patients may
      account for their high risk of cardiovascular events.

PMID- 14666956
TI  - Early benefit from structured care with atorvastatin in patients with coronary
      heart disease and diabetes mellitus.
AB  - This is a prospective evaluation of the effect of structured care of dyslipidemia
      with atorvastatin (strict implementation of guidelines) versus usual care
      (physician's standard of care) on morbidity and mortality of patients with
      coronary heart disease (CHD) and diabetes mellitus (DM). From 1600 consecutive
      CHD patients randomized to either form of care in the GREek Atorvastatin and CHD
      Evaluation Study (GREACE), 313 had DM: 161 in the structured care arm and 152 in
      the usual care arm. All patients were followed up for a mean of 3 years. In the
      structured care group, patients were treated with atorvastatin to achieve the
      National Cholesterol Education Program (NCEP) low-density lipoprotein cholesterol
      (LDL-C) treatment goal of <2.6 mmol/L (100 mg/dL). Primary endpoints were all
      cause and coronary mortality, coronary morbidity, and stroke. In the structured
      care group, 156 patients (97%) were taking atorvastatin (10-80 mg/day; mean, 23.7
      mg/day) throughout the study; the NCEP LDL-C treatment goal was reached by 150
      patients (93%). Only 17% (n=26) of the usual care patients were on long-term
      hypolipidemic drug treatment and 4% (n=6) reached the NCEP LDL-C treatment goal.
      During the study, 46 of 152 (30.3%) CHD patients with DM on usual care
      experienced a major vascular event or died versus 20 of 161 (12.5%) patients on
      structured care; relative risk reduction (RRR) 58%, p<0.0001. RRR for all-cause
      mortality was 52%, p=0.049; coronary mortality 62%, p=0.042; coronary morbidity
      59%, p<0.002; and stroke 68%, p=0.046. Event rate curves started deviating from
      the sixth treatment month and the RRR was almost 60% by the 12th month. RRRs
      remained at that level until the end of the study, when they became statistically
      significant. The cost/life-year gained with structured care was estimated at 6200
      US dollars. In CHD patients with DM, structured care of dyslipidemia with
      atorvastatin to achieve the NCEP LDL-C treatment goal, reduces all-cause and
      coronary mortality, coronary morbidity, and stroke by more than one half within a
      3-year period, in comparison to usual care. Clinical benefit is manifested as
      early as the sixth month of treatment.

PMID- 14666957
TI  - Increasing circulation in the lower limb under general anesthesia using the A-V
      impulse system.
AB  - The action of foot impulse technology (FIT) in reducing the risk of deep vein
      thrombosis (DVT) is well established. We hypothesized that intraoperative use of
      FIT devices will be effective in the prophylaxis of DVT. The aim of this study
      was to investigate the effect of a FIT device (A-V impulse system) on the venous
      flow of the lower extremity using duplex ultrasound scanning while the patient
      was under general anesthesia. Thirteen surgical patients who had no lower limb
      vessel lesions were selected for the study. Duplex scanning was used to measure
      blood velocity in the right common femoral vein, with and without the foot pump,
      before and during general anesthesia. The mean resting velocity was 33.2 +/- 5.5
      cm/sec in the pre-anesthetic state, 32.1 +/- 4.2 cm/sec under anesthetic, and
      30.4 +/- 5.0 cm/sec postoperatively. The peak velocities with the pump active
      were 38.6 +/- 5.0 cm/sec before anesthetic, 54.6 +/- 5.9 cm/sec while
      anesthetized, and 52.7 +/- 7.8 cm/sec postoperatively. The measured increases
      while under anesthesia and postoperatively both reached statistical significance
      (p<0.05). Our study demonstrated that use of the A-V impulse system causes a
      statistically significant increase in venous velocity of the lower extremity
      while the patient is under general anesthesia.

PMID- 14666958
TI  - Division or occlusion of patent ductus arteriosus?
AB  - The traditional and most effective form of treatment of persistent ductus
      arteriosus is surgical ductal division. New therapeutic techniques such as
      intraluminal ductal occlusion are currently recommended to replace the
      traditional treatment procedure. The purpose of this paper is to analyze the
      state of the art of these new therapeutic modalities. From reports in the medical
      literature, the authors analyzed the indications, results, and complications of
      the intraluminal ductal occlusion procedures. They applied the Student's t test
      for independent samples to evaluate the results of intraluminal patent ductus
      arteriosus occlusion by means of umbrellas, buttons, coils, and Gianturco-Grifka
      and Amplatzer occluders, respectively, in 2,691 patients collected from the
      medical literature. According to their analysis the results of intraluminal
      ductal occlusion with coils were as follows: success 83.7 +/- 12.2%, failure 3.9
      +/- 2.8%, incomplete ductal occlusion 17.5 +/- 15.3%, need for surgery 2.8 +/-
      3.8%, need for a second intraluminal procedure 5.8 +/- 9.9%, and device
      embolization 6.2 +/- 7.2%. The use of the Gianturco-Grifka device showed the
      following results: success 96.0 +/- 5.6%, failure 4.0 +/- 5.6%, incomplete ductal
      occlusion 4.0 +/- 5.6%, need for surgery 0%, need for a second intraluminal
      procedure 4.0 +/- 5.6%, and device embolization 4.0 +/- 5.6%. The Amplatzer
      occluder showed the following results: success 92.8 +/- 6.1%, failure 7.2 +/-
      6.1%, incomplete ductal occlusion 2.0 +/- 4.3%, need for surgery 0%, need for a
      second intraluminal procedure 0.8 +/- 1.7%, and device embolization 0.5 +/- 1.3%.
      According to the state of the art, intraluminal ductal occlusion with Gianturco
      Grifka device and Amplatzer occluder reduces the proportion of incomplete
      obstructions and need for surgery. Additionally, the use of the Amplatzer
      occluder reduces need for a second procedure and the embolization rate. Although
      the results obtained with the new procedures are better than those obtained
      previously, they are still not totally satisfactory.

PMID- 14666959
TI  - Effect of intracoronary estradiol on postischemic microvascular damage in a
      porcine model: a myocardial contrast echocardiographic study.
AB  - Coronary microvascular damage can occur in the presence of myocardial ischemia
      even if epicardial vessels are patent, a phenomenon known as "no-reflow."
      Estrogens have favorable effects on coronary conductance and resistance arteries,
      and may have therapeutic value in ischemic syndromes. Myocardial contrast
      echocardiography (MCE) is a promising method for evaluating microvascular damage.
      In this study, the authors hypothesized that acute intracoronary 17beta-estradiol
      administration can reduce postischemic microvascular damage, which is evaluated
      by MCE, in a porcine model. Sixteen male pigs were randomized into 2 groups: the
      treatment group (n = 9) received intracoronary estradiol in increasing doses, and
      the control group (n = 7) received intracoronary vehicle (dimethylsulfoxide,
      DMSO). Microvascular damage was induced by balloon catheter occlusion followed by
      reperfusion of the left circumflex coronary artery (LCX). MCE using Levovist with
      harmonic imaging was performed before and during 15-minute balloon occlusion of
      the proximal LCX to determine perfusion areas of the left anterior descending
      artery (LAD) and LCX. MCE was performed immediately postocclusion and after each
      injection of estradiol (1, 10, and 100 nmol/L) or DMSO. Videodensitometry
      measurements were performed as a quantitative marker for myocardial microvascular
      damage. Videodensitometry results were expressed as peak intensity ratios.
      Intracoronary estradiol induced a significant reduction in myocardial
      microvascular damage after ischemic episode by videodensitometry measurements
      when compared to intracoronary DMSO. The authors conclude that intracoronary
      injection of estradiol reduces postischemic microvascular damage measured by MCE
      in a porcine model.

PMID- 14666960
TI  - A pedigree analysis of familial hypercholesterolemia in monozygote twin brothers.
AB  - The current study was designed to investigate the features of a family with
      familial hypercholesterolemia (FH). Twenty members of 3 generations in a family
      with hypercholesterolemia were enrolled in the study. The data collected were
      from clinical observation and subjected to pedigree analysis. The proband was a
      41-year-old male who suffered from angina pectoris with multi-vessel stenosis of
      coronary arteries at the age of 40. Among 20 members, 8 individuals had FH in
      this family with a total incidence of 40% (54.5% [6/11] in male and 22.2% [2/9]
      in female). The serum total cholesterol level was increased in childhood from 7.1
      to 10.8 mmol/L and tended to increase with increasing age. In addition, the level
      of total cholesterol was increased in monozygote twin brothers and their
      offspring in the family. This pedigree analysis showed that FH appears to be a
      hereditary disease of autosomal dominance, and attention should be paid,
      especially in the only son or daughter society of China.

PMID- 14666961
TI  - Aortic dissection after aortic valve replacement--a case report and literature
      review.
AB  - Type A aortic dissection occurs in 0.6% of patients late after aortic valve
      replacement. However, little information is available about risk factors for
      developing this complication, nor are recommendations for elective replacement of
      the ascending aorta available. The authors present a 78-year-old woman who
      developed type A aortic dissection thirty months after aortic valve replacement;
      ascending aorta was normal at the time of aortic valve replacement.

PMID- 14666962
TI  - Spontaneous coronary artery dissection in a woman receiving 5-fluorouracil--a
      case report.
AB  - A 39-year-old woman with cervical cancer treated with pelvic radiation therapy
      and 5-fluorouracil (5-FU) was hospitalized for dehydration and intractable
      vomiting. She developed an acute ST-elevation myocardial infarction (MI) that
      extended electrocardiographically after thrombolytic therapy. Coronary
      angiography demonstrated a completely occluded left anterior descending (LAD)
      artery with extensive coronary dissection that was treated successfully with
      stenting. The authors discuss several factors that may have contributed to the
      spontaneous coronary artery dissection (SCAD) including chemotherapy-induced
      vasospasm, hemodynamic stress of vomiting, and hormonal changes associated with
      pelvic radiation.

PMID- 14666963
TI  - Sinus node dysfunction in a heart transplant patient secondary to severe sinus
      node artery obstruction--a case report.
AB  - A case of sinus node dysfunction is reported secondary to severe sinus node
      artery obstruction 3 years after orthotopic heart transplantation. The patient
      first presented with frequent dizzy spells and presyncopal episodes for 3 months
      and then recurrent syncope in the presence of an acute myocardial infarction.
      Coronary angiography showed a diffusely narrowed sinus node artery without any
      apparent collateral vessels. The sinus node artery had had only minimal distal
      disease 3 months previously. A dual chamber permanent pacemaker was implanted
      with significant improvement in clinical symptoms.

PMID- 14666964
TI  - Polymyositis complicated with complete atrioventricular block--a case report and
      review of the literature.
AB  - A 35-year-old woman, diagnosed with polymyositis about 5 years before was
      admitted to the authors' clinics with syncope attack due to complete
      atrioventricular (AV) block. Progression of left bundle branch block to complete
      AV block despite all immune-suppressive treatment, and rarity of this
      complication in patients with polymyositis prompted the authors to report this
      case.

PMID- 14666965
TI  - Coronary arteriomegaly in a patient with Ehlers-Danlos syndrome and multiple
      aneurysms--a case report.
AB  - The authors report a case of coronary arteriomegaly in a patient with Ehlers
      Danlos syndrome and multiple aneurysms who presented with myocardial infarction.
      Coronary arteriography revealed distal "pruning" of vessels without occlusive
      disease. Fibroblast cultures excluded Ehlers-Danlos syndrome types IV and VII.
      Literature review suggests this may represent a previously unidentified vascular
      syndrome.

PMID- 14666966
TI  - HMGI(Y) gene expression in colorectal cancer: comparison with some histological
      typing, grading, and clinical staging.
AB  - We investigated HMGI(Y) gene expression in 81 pairs of frozen samples obtained
      from colorectal carcinomas and adjacent normal colorectal mucosas and in four
      samples from colorectal mucosa from patients without neoplastic diseases. In this
      group, HMGI(Y)-positive/-negative expression was compared with some histological
      features, grading, and clinical staging of neoplasms investigated to assess its
      potential role as a prognostic marker for colorectal cancer. Expression of
      HMGI(Y) gene was found in 51 of 81 cases of colorectal cancers, while, in normal
      mucosa, expression of this gene was not observed. HMGI(Y) gene expression was
      associated with more advanced tumors (T3, T4) and metastases to lymph nodes (N1,
      N2). The most interesting finding was that expression of this gene correlated
      with distant metastases. HMGI(Y) gene expression was detected in all cases
      classified as M1 (n = 19, p = 0.0008). We did not find any association between
      age, gender, tumor localization, histological type and this gene expression.

PMID- 14666967
TI  - The relationship between primary gastric B-cell lymphoma and immunoglobulin heavy
      chain (IgH) gene rearrangement--a histopathological study of primary gastric
      lymphomas.
AB  - The aim of this study was to review our primary gastric lymphoma cases according
      to the new WHO classifications and to investigate the histopathological features
      of B-cell lymphomas. In addition, B-cell monoclonality was analyzed for
      immunoglobulin heavy chain (IgH) gene rearrangement using the polymerase chain
      reaction at the site of the lymphoma lesion, transitional lesion, and the non
      lymphoma lesion. Specimens resected from 31 primary gastric lymphomas were
      examined. There were 28 cases (90.3%) of B-cell lymphoma and three cases (9.7%)
      of T-cell lymphoma. The B-cell lymphomas were classified as low-grade mucosa
      associated lymphoid tissue (MALT) lymphoma (LGML) (9%), high-grade MALT lymphoma
      (HGML) (42%), and diffuse large B-cell lymphoma (DLBCL) (29%).
      Histopathologically, lymphoepithelial lesions (LEL) were higher in LGML (100%)
      than in DLBCL (22%), with statistical significance (p < 0.05). A monoclonal
      pattern of IgH rearrangement was detected in LGML (50.0%), HGML (60.0%), and
      DLBCL (80.6%), with a statistically significant difference between LGML and DLBCL
      (p < 0.01). The IgH monoclonal pattern may reflect the gross appearance of
      lymphoma or the lymphoma infiltration depth. Superficial spreading and shallow
      growth in LGML may correspond to an oligoclonal pattern, and mass-forming and
      deep invasive growth in DLBCL may correspond to a more monoclonal pattern.

PMID- 14666968
TI  - Elevated E-cadherin and alpha/beta-catenin expression after androgen deprivation
      therapy in prostate adenocarcinoma.
AB  - The histological patterns of anti-androgen-treated prostate adenocarcinoma mimic
      high grade tumors classified according to the widely used Gleason scoring system.
      However, the biological characteristics of anti-androgen treated carcinoma are
      largely unknown. E-cadherin, alpha-catenin, and beta-catenin adhesion molecules
      are down-regulated in pharmacologically untreated high grade prostate carcinoma.
      In this study, we used immunohistochemical techniques to investigate their
      expression in twenty acinar adenocarcinomas after anti-androgen therapy in
      prostatectomy specimens. After adrogen ablation therapy, expression of all these
      adhesion molecules was higher than that of pretreatment biopsies of the same
      patient group and high grade matched untreated controls. These results emphasize
      the inaccuracy of the Gleason score for anti-androgen-treated prostate
      adenocarcinoma and the more differentiated phenotype of prostate adenocarcinoma
      after anti-hormonal therapy.

PMID- 14666969
TI  - Flow cytometric cerebrospinal fluid analysis in children.
AB  - Flow cytometry (FC) is of increasing importance for the analysis of cerebrospinal
      fluid (CSF) lymphocytes because of its ability to detect a large spectrum of
      cellular characteristics (granularity, volume, surface antigen expression) even
      in small amounts of cells. Data on CSF FC in children are very limited. Here, we
      summarize our 3-year experience of CSF FC routinely performed in pediatric
      patients with assumed inflammatory central nervous system (CNS) disease. Among
      109 samples sent for analysis, flow cytometric detection of major leukocyte
      subsets was possible in 78% (85 out of 109), which exceeds the 31% rate of our
      retrospective microscopic pediatric control group. Apart from physiologic
      lymphocytes (100%) or monocytes (48%), 11 out of these 85 samples showed
      granulocytes, two showed proliferated monocytes, and nine displayed proliferated
      lymphocytes. In most children, the proliferated lymphocytes consisted of a
      polyclonal population of CD4+ and CD8+ T cells. Compared with literature data,
      eight children showed abnormally composed lymphocyte subsets (surface antigen
      expression) within the main lymphocyte population. However, none of these changes
      was specific for distinct diseases or allowed a distinction between patients with
      and without primary inflammatory processes. These data suggest that CSF FC may be
      the most effective modality to differentiate major CSF leukocyte subsets. At
      present, further differentiation of distinct cell populations, such as
      proliferated lymphocytes, is of limited clinical impact. This may, however, gain
      increasing interest in the future.

PMID- 14666970
TI  - Effect of prenatal phenytoin administration on the fine structure of rat
      myocardium and aorta.
AB  - Phenytoin (PHT) is an antiepileptic drug known to have teratogenic effects. The
      aim of this study was to examine the ultrastructure of the left ventricle, the
      left atrium, and the aorta of 3-month-old offspring and 4-month-old mother
      animals after oral PHT (150 mg/kg/day) administration to Wistar/DV rats on days 7
      18 of gestation. Electron microscopy of the myocardium revealed a heterogeneous
      population of cardiomyocytes with conventional architecture, and hypoxia/ischemia
      like subcellular changes. Cardiomyocytes of offspring hearts were more vulnerable
      to PHT administration compared with the mother animals. Atrial cardiomyocytes of
      both mother animals and offspring were less affected by PHT than the ventricular
      ones. In the myocardium, both interstitial fibrosis and injury of capillaries
      were noted. Electron microscopy of the aorta revealed a higher resistance of
      maternal endothelial and smooth muscle cells to PHT compared with offspring
      cells. Nuclei of endothelial and smooth muscle cells showed pronounced mitotic
      activity with one and/or two hyperactive nucleoli, more frequently observed in
      offspring. PHT administration resulted in aortic arteriogenesis in both offspring
      and mother animals. Interestingly, bundles of myocardial fibers consisting of
      ischemia-like altered cardiomyocytes with own capillary network were noted in off
      spring aortic adventitia. These results are indicative of harmful effects of PHT
      on rat myocardium and aorta.

PMID- 14666971
TI  - Solitary fibrous tumor of the thyroid with capsular invasion.
AB  - This report describes the clinical and pathologic findings of a peculiar case of
      solitary fibrous tumor of the thyroid gland that showed capsular invasion. After
      four and a half years of follow-up, neither local recurrence nor metastasis has
      developed.

PMID- 14666972
TI  - Autoimmune disease-associated lymphadenopathy from dermatomyositis. A case
      report.
AB  - A case of autoimmune disease-associated lymphadenopathy (ADAL) in the lymph nodes
      linked to well documented dermatomyositis is presented. A 49-year-old Japanese
      woman was affected by a left axillary and a left inguinal lymphadenopathy at the
      onset of disease. A biopsy specimen taken from a left inguinal lymph node showed
      distortion of the nodal architecture and polymorphous lymphoid infiltration
      containing many plasma cells and plasmacytoid cells with scattered transformed
      lymphocytes, as well as a large number of capillaries. The polytypic nature of B
      lymphocytes was demonstrated by immunohistochemistry and polymerase chain
      reaction. Epstein-Barr virus-associated lymphoplasmacytic infiltrates may occur
      in patients immunosuppressed by methotrexate administered for the treatment of
      dermatomyositis. However, Epstein-Barr virus-encoded small RNA-positive cells
      were not identified by in situ hybridization. Moreover, the patient had no
      history of methotrexate therapy.

PMID- 14666973
TI  - An unusual coincidence of multiple synchronous kidney tumors with a metachronous
      rectal adenocarcinoma.
AB  - In synchronous surgery specimens (right-sided nephrectomy and left-sided partial
      nephrectomy), a unique combination of a papillary (chromophil) renal cell
      carcinoma (4 x 3.7 x 3.5 cm) and a renal oncocytoma (11 x 10 x 9 mm) in the right
      kidney and a renal carcinoid (2.5 x 2.3 x 1.1 cm) in the resected part of the
      left kidney has been found. This multiplicity and bilaterality, based on the
      findings of three distinct histogenetic types of kidney tumors, was accompanied
      by a metachronous rectal adenocarcinoma discovered 14 months later. After
      surgery, no radiation or other oncologic therapy was given. At present, our
      patient is well without any evidence of neoplastic disease three years after
      primary diagnosis. To the best of our knowledge, this is the first case of a
      combination of three distinct histogenetic types of synchronous renal tumors
      associated with a metachronous rectal adenocarcinoma treated with simple surgery.
      In the absence of cytogenetic studies, the possibility of a the presence of a
      hereditary renal cancer syndrome must be considered.

PMID- 14666974
TI  - The variable part of the dnaK gene as an alternative marker for phylogenetic
      studies of rhizobia and related alpha Proteobacteria.
AB  - DnaK is the 70 kDa chaperone that prevents protein aggregation and supports the
      refolding of damaged proteins. Due to sequence conservation and its ubiquity this
      chaperone has been widely used in phylogenetic studies. In this study, we applied
      the less conserved part that encodes the so-called alpha-subdomain of the
      substrate-binding domain of DnaK for phylogenetic analysis of rhizobia and
      related non-symbiotic alpha-Proteobacteria. A single 330 bp DNA fragment was
      routinely amplified from DNA templates isolated from the species of the genera,
      Azorhizobium, Bradyrhizobium, Mesorhizobium, Rhizobium and Sinorhizobium, but
      also from some non-symbiotic alpha Proteobacteria such as Blastochloris,
      Chelatobacter and Chelatococcus. Phylogenetic analyses revealed high congruence
      between dnaK sequences and 16S rDNA trees, but they were not identical. In
      contrast, the partition homogeneity tests revealed that dnaK sequence data could
      be combined with other housekeeping genes such as recA, atpD or glnA. The dnaK
      trees exhibited good resolution in the cases of the genera Mesorhizobium,
      Sinorhizobium and Rhizobium, even better than usually shown by 16S rDNA
      phylogeny. The dnaK phylogeny supported the close phylogenetic relationship of
      Rhizobium galegae and Agrobacterium tumefaciens (R. radiobacter) C58, which
      together formed a separate branch within the fast-growing rhizobia, albeit closer
      to the genus Sinorhizobium. The Rhizobium and Sinorhizobium genera carried an
      insertion composed of two amino acids, which additionally supported the
      phylogenetic affinity of these two genera, as well as their distinctness from the
      Mesorhizobium genus. Consistently with the phylogeny shown by 16S-23S rDNA
      intergenic region sequences, the dnaK trees divided the genus Bradyrhizobium into
      three main lineages, corresponding to B. japonicum, B. elkanii, and
      photosynthetic Bradyrhizobium strains that infect Aeschynomene plants. Our
      results suggest that the 330 bp dnaK sequences could be used as an additional
      taxonomic marker for rhizobia and related species (alternatively to the 16S rRNA
      gene phylogeny).

PMID- 14666975
TI  - Effect of food processing on the fate of DNA with regard to degradation and
      transformation capability in Bacillus subtilis.
AB  - Soymilk, tofu, corn masa, and cooked potato were produced from transgenic raw
      materials and the effect of processing on the degradation of DNA was studied.
      Major degrading factors were for soymilk and tofu the mechanical treatment of
      soaked soybeans and for corn masa and cooked potatoes the thermal treatment. In
      the processed foods no DNA fragments > 1.1 kb were detected. We included in our
      studies the effect of the size of donor DNA and length of the homologous sequence
      on the marker rescue transformation of B. subtilis LTH 5466, which was monitored
      by restoration of deleted nptII. When DNA fragments (168, 414, 658, and 792 bp)
      of nptII and linearized plasmid DNA (pGEM-T-1, 3168 bp and pGEM-T-2, 3792 bp)
      containing the 168 bp or 792 bp fragments, respectively, were used as donor DNA,
      it was observed that the efficiency of marker rescue decreased with decreasing
      length of homologous sequence. The use of a larger plasmid (pMR2, 5786 bp)
      containing the 792 bp fragment revealed higher efficiency of marker rescue
      compared to pGEM-T-2. The nptII fragments resulted in lower efficiencies compared
      to plasmid DNA containing the same fragment. For the 792 bp fragment and the
      linearized plasmid pMR2 a first-order dependency of the frequency of marker
      rescue transformation on the DNA concentration was observed. Based on the
      acquired data, the hypothetical frequency of transformation of transgenic DNA to
      B. subtilis in cooked potatoes was calculated to be equal to 8.5 x 10(-19) and
      1.2 x 10(-27) for homologous and illegitimate recombination, respectively. These
      data permit to roughly estimate the time after which a person (10(8) years) or
      the world population (15 days) is exposed to one transformant generated by
      homologous recombination event, when the daily consumption per person is 130 g of
      cooked potatoes.

PMID- 14666976
TI  - Cry29A and Cry30A: two novel delta-endotoxins isolated from Bacillus
      thuringiensis serovar medellin.
AB  - Two novel crystal protein genes from a highly mosquitocidal Bacillus
      thuringiensis serovar medellin strain were cloned and sequenced. The
      corresponding proteins, Cry29A and Cry30A, were nontoxic when tested individually
      against the mosquito species bioassayed (Aedes aegypti, Culex pipiens and
      Anopheles stephensi). However, Cry29A synergized the toxicity of Cry11Bb against
      Aedes aegypti by a four-fold factor.

PMID- 14666977
TI  - Psychrophilic Planococcus maitriensis sp.nov. from Antarctica.
AB  - An orange pigmented bacterium, S1, was isolated from a cyanobacterial mat sample
      collected in the vicinity of Schirmacher Oasis, Maitri, the Indian station, in
      Antarctica. The bacterium is Gram-positive and possesses all the characteristics
      of the genus Planococcus. It is non-sporulating, motile and has A4alpha type
      peptidoglycan, MK-7 and MK-8 as the major menaquinones and anteiso-C(15:0) as the
      major fatty acid. Based on the phylogenetic characteristics, the bacterium S1 is
      identified as a close relative of Planococcus citreus with which it shares 98.12%
      similarity at the 16S rRNA gene level but exhibits a low similarity of 52% at the
      whole genome level. Apart from the above major differences, S1 also exhibits
      phenotypic differences with Planococcus citreus and other members of the genus
      Planococcus. Based on these differences, the bacterium S1 is identified as a new
      species of the genus Planococcus for which the name Planococcus maitriensis is
      proposed. The type strain of Planococcus maitriensis is S1(T) (= MTCC 4827; DSM
      15305).

PMID- 14666978
TI  - Actinomadura mexicana sp. nov. and Actinomadura meyerii sp. nov., two novel soil
      sporoactinomycetes.
AB  - The taxonomic position of two soil isolates, strains A288(T) and A290(T)
      [provisionally assigned to the genus Actinomadura] was clarified in a polyphasic
      study. The organisms showed a combination of chemotaxonomic and morphological
      properties typical of actinomadurae. They also formed distinct phyletic lines in
      the 16S rRNA Actinomadura gene tree; strain A288(T) was associated with A.
      nitritigenes whereas strain A290(T) was closely related to a group that consisted
      of A. citrea, A. coerulea, A. glauciflava, A. luteofluorescens and A.
      verrucosospora. Strains A288(T) and A290(T) showed key phenotypic features which
      readily distinguish them from one another and from representatives of related
      validly described species of Actinomadura. It is proposed that the two organisms
      be classified as new species of the genus Actinomadura. The names proposed for
      the new taxa are Actinomadura mexicana (A290(T) = DSM 44485(T) = NRRL B
      24203(T)), and Actinomadura meyerii (A288(T) = DSM 44485(T) = NRRL B-24203(T)).

PMID- 14666979
TI  - Actinomyces hongkongensis sp. nov. a novel Actinomyces species isolated from a
      patient with pelvic actinomycosis.
AB  - A bacterium was isolated from the pus of a patient with pelvic actinomycosis. The
      cells were strictly anaerobic, straight, non-sporulating, Gram-positive rods. It
      grows on sheep blood agar as non-haemolytic, pinpoint colonies after 24 hours of
      incubation at 37 degrees C in anaerobic environment. It is non-motile and does
      not produce catalase. 16S ribosomal RNA (rRNA) gene sequencing showed that there
      were 6.6% difference between the 16S rRNA gene sequence of the bacterium that of
      Actinomyces marimammalium (GenBank Accession no. AJ276405), a new species
      described in 2001, isolated from two seals and a porpoise. For these reasons a
      new species, Actinomyces hongkongensis sp. nov., is proposed, for which HKU8(T)
      is the type strain. Further studies should be performed to ascertain the
      potential of this bacterium to become an important cause of actinomycosis.

PMID- 14666980
TI  - Chryseobacterium miricola sp. nov., a novel species isolated from condensation
      water of space station Mir.
AB  - Classification of strain W3-B1, which was isolated from condensation water in the
      Russian space laboratory Mir, was investigated by a polyphasic taxonomic
      approach. Cells of strain W3-B1 were nonmotile, asporogenous, gram-negative
      slender rods with rounded ends. 16S rRNA gene sequence analysis indicated that
      organism should be placed in the genus Chryseobacterium. This organism contains
      menaquinone MK-6 as the predominent isoprenoid quinone and 3-OH iso 17:0 (40%),
      iso 15:0 (33%) as the major fatty acids. Phylogenetically, the nearest relative
      of strain W3-B1 is Chryseobacterium meningosepticum with sequence similarity of
      98.4%, but DNA-DNA hybridization resulted in similarity values of only 52.3%. The
      G+C mol% is 34.6 mol%. Based upon results obtained by morphological, biochemical,
      chemotaxonomic, and molecular methods, strain W3-B1 was clearly distinguishable
      from other Chryseobacterium species. For these reasons, a novel species of family
      Flavobacteriaceae is proposed; strain W3-B1(T) (= GTC 862(T) = JCM 11413(T) = DSM
      14571(T)) is the type strain.

PMID- 14666981
TI  - Candidatus "Scalindua brodae", sp. nov., Candidatus "Scalindua wagneri", sp.
      nov., two new species of anaerobic ammonium oxidizing bacteria.
AB  - Anaerobic ammonium oxidation (anammox) is both a promising process in wastewater
      treatment and a long overlooked microbial physiology that can contribute
      significantly to biological nitrogen cycling in the world's oceans. Anammox is
      mediated by a monophyletic group of bacteria that branches deeply in the
      Planctomycetales. Here we describe a new genus and species of anaerobic ammonium
      oxidizing planctomycetes, discovered in a wastewater treatment plant (wwtp)
      treating landfill leachate in Pitsea, UK. The biomass from this wwtp showed high
      anammox activity (5.0 +/- 0.5 nmol/mg protein/min) and produced hydrazine from
      hydroxylamine, one of the unique features of anammox bacteria. Eight new
      planctomycete 16S rRNA gene sequences were present in the 16S rRNA gene clone
      library generated from the biomass. Four of these were affiliated to known
      anammox 16S rRNA gene sequences, but branched much closer to the root of the
      planctomycete line of descent. Fluorescence in situ hybridization (FISH) with
      oligonucleotide probes specific for these new sequences showed that two species
      (belonging to the same genus) together made up > 99% of the planctomycete
      population which constituted 20% of the total microbial community. The
      identification of these organisms as typical anammox bacteria was confirmed with
      electron microscopy and lipid analysis. The new species, provisionally named
      Candidatus "Scalindua brodae" and "Scalindua wagneri" considerably extend the
      biodiversity of the anammox lineage on the 16S rRNA gene level, but otherwise
      resemble known anammox bacteria. Simultaneously, another new species of the same
      genus, Candidatus "Scalindua sorokinii", was detected in the water column of the
      Black Sea, making this genus the most widespread of all anammox bacteria
      described so far.

PMID- 14666982
TI  - Characterisation of persistent and sporadic Listeria monocytogenes strains by
      pulsed-field gel electrophoresis (PFGE) and amplified fragment length
      polymorphism (AFLP).
AB  - This study was set up to evaluate the genetic similarity or dissimilarity of
      persistent and sporadic Listeria monocytogenes strains existing in eleven food
      processing facilities, including fish, dairy, meat and poultry processing plants.
      In each plant persistent and sporadic strains were selected on the basis of PFGE
      typing results. A total of 17 strains representing persistent strains and 38
      sporadic strains originating from eleven food processing plants were included in
      the study. PFGE macrorestriction patterns of persistent and sporadic strains from
      different processing plants were compared and the strains were further studied by
      amplified fragment length polymorphism (AFLP), being a characterisation method
      giving more whole genome based information. The 17 persistent and 38 sporadic
      strains showed 14 and 35 pulsotypes, 14 and 28 AFLP types, respectively. The
      combination of PFGE and AFLP typing results yielded a total of 48 genotypes.
      Thirteen of 15 genotypes presented by persistent strains were only associated
      with persistent strains and similarly 94% (33/35) of genotypes showed by sporadic
      strains were recovered among sporadic strains only. Our results showed that L.
      monocytogenes strains causing persistent contamination differ from sporadic
      strains. In AFLP analysis persistent strains did not, however, form any specific
      clusters and neither was there any difference between the known two genomic
      groups. These results indicate that even though persistent strains differ from
      sporadic strains there seems not to be any specific evolutional lineage of
      persistent strains.

PMID- 14666983
TI  - Identification of Carnobacterium, Lactobacillus, Leuconostoc and Pediococcus by
      rDNA-based techniques.
AB  - Ribosomal DNA-based techniques including the analysis of profiles generated by
      ISR amplification, ISR restriction and ARDRA have been evaluated as molecular
      tools for identifying Carnobacterium, Lactobacillus, Leuconostoc and Pediococcus.
      They have been applied for the molecular characterization of 91 strains with the
      following identities: eight Carnobacterium including the eight type species of
      the genus; 61 Lactobacillus including 40 type strains out of 45 species, 13
      Leuconostoc, out of them 11 are type strains and three are subspecies of Lc.
      mesenteroides; and nine strains representing the six species of genus
      Pediococcus. The genetic relationship displayed between these species by rrn
      based profiles is sustained by their phylogenetic relationships and can therefore
      be considered useful for taxonomic purposes. Profiles obtained by ISR
      amplification allowed identification at genus level of Carnobacterium and
      Leuconostoc, and even at species level in genus Carnobacterium. Genera
      Lactobacillus and Pediococcus could not be distinguished from each other by
      applying this technique. The Lactobacillus species analysed here (45) were
      differentiated using ARDRA-DdeI and ISR-DdeI profiles, sequentially, and
      Pediococcus species by ISR-DdeI profiles. It was necessary to combine profiles
      generated by restriction of ISR-DdeI, ARDRA-DdeI and ARDRA-HaeIII in order to
      complete the identification of Leuconostoc species.

PMID- 14666984
TI  - Identification of Bifidobacterium species using rep-PCR fingerprinting.
AB  - The aim of the present study was to evaluate the use of repetitive DNA element
      PCR fingerprinting (rep-PCR) for the taxonomic discrimination among the currently
      described species within the genus Bifidobacterium. After evaluating several
      primer sets targeting the repetitive DNA elements BOX, ERIC, (GTG)s and REP, the
      BOXA1R primer was found to be the most optimal choice for the establishment of a
      taxonomical framework of 80 Bifidobacterium type and reference strains.
      Subsequently, the BOX-PCR protocol was tested for the identification of 48
      unknown bifidobacterial isolates originating from human faecal samples and
      probiotic products. In conclusion, rep-PCR fingerprinting using the BOXA1R primer
      can be considered as a promising genotypic tool for the identification of a wide
      range of bifidobacteria at the species, subspecies and potentially up to the
      strain level.

PMID- 14666985
TI  - The taxonomic position of Saccharomyces boulardii as evaluated by sequence
      analysis of the D1/D2 domain of 26S rDNA, the ITS1-5.8S rDNA-ITS2 region and the
      mitochondrial cytochrome-c oxidase II gene.
AB  - A taxonomic study was carried out on eight strains of Saccharomyces boulardii.
      Morphological and physiological characteristics were consistent with those of
      Saccharomyces cerevisiae. Sequences of the D1/D2 domain of the 26S rDNA were
      identical for all strains examined and had a similarity value of 100% compared to
      sequences of the type strain of S. cerevisiae (CBS 1171T) and strain S288c. For
      all S. boulardii isolates was found the exact same ITS1-5.8S rDNA-ITS2 sequence,
      which displayed a close resemblance with the sequences published for S288c
      (99.9%), CBS 1171(T) (99.3%) and other S. cerevisiae strains. Sequence analysis
      of the mitochondrial cytochrome-c oxidase II gene (COX2) also resulted in
      identical sequences for the S. boulardii isolates and comparisons with available
      nucleotide sequences revealed close relatedness to strains of S. cerevisiae
      including S288c (99.5%) and CBS 1171(T) (96.6%). The electrophoretic karyotypes
      of the S. boulardii strains appeared quite uniform and although very typical of
      S. cerevisiae, they formed a cluster separate from strains of this species. The
      results of the present study strongly indicate a close relatedness of S.
      boulardii to S. cerevisiae and thereby support the recognition of S. boulardii as
      a member of S. cerevisiae and not as a separate species.

PMID- 14666986
TI  - Molecular approaches for the detection and identification of bifidobacteria and
      lactobacilli in the human gastrointestinal tract.
AB  - In this review an overview of various molecular techniques and their application
      for the detection and identification of bifidobacteria and lactobacilli in the
      gastrointestinal (GI) tract is presented. The techniques include molecular typing
      techniques such as amplified ribosomal DNA restriction analysis (ARDRA), randomly
      amplified polymorphic DNA (RAPD), pulsed field gel electrophoresis (PFGE),
      ribotyping and community profiling techniques such as PCR coupled to temperature
      and denaturing gradient gel electrophoresis (PCR-TGGE and PCR-DGGE,
      respectively). Special attention is given to oligonucleotide probes and primers
      that target the ribosomal RNA (rRNA) sequences and their use in PCR and different
      hybridisation techniques such as DNA microarrays and fluorescent in situ
      hybridisation (FISH). In addition, recent findings based on the molecular studies
      of bifidobacteria and lactobacilli in the GI-tract are reviewed.

PMID- 14666987
TI  - Genetic and ecological structure of Hafnia alvei in Australia.
AB  - Multilocus enzyme electrophoresis of 161 Hafnia alvei isolates from 158 hosts and
      3 water column samples collected in Australia revealed that this species consists
      of two genetically distinct groups. The two groups of H. alvei differed
      significantly in their genetic structure and host distribution. The taxonomic
      class of the host but not geographic locality explained a significant proportion
      of the observed genetic and biochemical variation among strains within each
      genetic group.

PMID- 14666988
TI  - Isolation of Burkholderia cepacia complex genomovars from waters.
AB  - The aim of this study was to develop a selective enrichment broth as an aid for
      the isolation of Burkholderia cepacia complex (Bcc) bacteria from water. To allow
      growth of all nine genomovars, mixtures of two carbon sources had to be used,
      i.e. L-arabinose/D-cellobiose or L-arabinose/L-threonine. Selectivity was
      provided by polymyxin B and 9-chloro-9-(4-diethylaminophenyl)-10-phenylacridan (C
      390). Following enrichment, Bcc bacteria were isolated on a diagnostic O/F agar
      supplemented with gentamicin. A preliminary bio-diversity study on 28 surface
      waters yielded five different genomovars, i.e. B. cepacia (genomovar I), B.
      multivorans, B. cenocepacia, B. vietnamiensis and B. anthina. Drinking waters did
      not contain Bcc bacteria. However, the genomovar pattern from a given sample
      varied with the enrichment broth used.

PMID- 14666989
TI  - Design and evaluation of specific PCR primers for rapid and reliable
      identification of Staphylococcus xylosus strains isolated from dry fermented
      sausages.
AB  - Rapid and reliable identification of Staphylococcus xylosus was achieved by
      species-specific PCR assays. Two sets of primers, targeting on xylulokinase
      (xylB) and 60 kDa heat-shock protein (hsp60) genes of S. xylosus, respectively,
      were designed. Species-specificity of both sets of primers was evaluated by using
      27 reference strains of the DSM collection, representing 23 different species of
      the Staphylococcus genus and 3 species of the Kocuria genus. Moreover, 90 wild
      strains isolated from different fermented dry sausages were included in the
      analysis. By using primers xylB-F and xylB-R the expected PCR fragment was
      obtained only when DNA from S. xylosus was used. By contrast, amplification
      performed by using primers xylHs-F and xylHs-R produced a single PCR fragment, of
      the expected length, when DNA from S. xylosus, S. haemolyticus, S. intermedius
      and S. kloosii were used as template. Nevertheless, AluI digestion of the xylHs
      F/xylHs-R PCR fragment allowed a clear differentiation of these 4 species. The
      rapidity (about 4 h from DNA isolation to results) and reliability of the PCR
      procedures established suggests that the method may be profitably applied for
      specific detection and identification of S. xylosus strains.

PMID- 14666990
TI  - Genetic diversity of bradyrhizobial populations from diverse geographic origins
      that nodulate Lupinus spp. and Ornithopus spp.
AB  - The genetic diversity of 45 bradyrhizobial isolates that nodulate several Lupinus
      and Ornithopus species in different geographic locations was investigated by 16S
      rDNA PCR-RFLP and sequence analysis, 16S-23S rDNA intergenic spacer (IGS) PCR
      RFLP analysis, and ERIC-PCR genomic fingerprinting. Reference strains of
      Bradyrhizobium japonicum, B. liaoningense and B. elkanii and some Canarian
      isolates from endemic woody legumes in the tribe Genisteae were also included.
      The 16S rDNA-RFLP analysis resolved 9 genotypes of lupin isolates, a group of
      fourteen isolates presented restriction-genotypes identical or very similar to B.
      japonicum, while another two main groups of isolates (69%) presented genotypes
      that clearly separated them from the reference species of soybean. 16S rDNA
      sequencing of representative strains largely agreed with restriction analysis,
      except for a group of six isolates, and showed that all the lupin isolates are
      relatives of B. japonicum, but different lineages were observed. The 16S-23S IGS
      RFLP analysis showed a high resolution level, resolving 19 distinct genotypes
      among 30 strains analysed, and so demonstrating the heterogeneity of the 16S-RFLP
      groups. ERIC-PCR fingerprint analysis showed an enormous genetic diversity
      producing a different pattern for each but two of the isolates. Phylogeny of nodC
      gene was independent from the 16S rRNA phylogeny, and showed a tight relationship
      in the symbiotic region of the lupin isolates with isolates from Canarian
      genistoid woody legumes, and in concordance, cross-nodulation was found. We
      conclude that Lupinus is a promiscuous host legume that is nodulated by rhizobia
      with very different chromosomal genotypes, which could even belong to several
      species of Bradyrhizobium. No correlation among genomic background, original host
      plant and geographic location was found, so, different chromosomal genotypes
      could be detected at a single site and in a same plant species, on the contrary,
      an identical genotype was detected in very different geographical locations and
      plants.

PMID- 14666991
TI  - Detection of ingested bacteria in benthic ciliates using fluorescence in situ
      hybridization.
AB  - Fluorescence in situ hybridization (FISH) was applied to detect ingested natural
      bacteria within the food vacuoles of ciliates harvested from the natural
      sediment. In addition to this important qualitative aspect, FISH was also
      successfully used to measure the bacterivory of a culture of the ciliate
      Tetrahymena pyriformis on natural field sediment bacteria. In this feeding
      experiment, we compared the FISH technique with the only available alternative
      technique using fluorescently stained sediment (FS-sediment). The ingestion rate
      of unstained sediment bacteria determined by FISH was 4.6 bacteria per ciliate
      and hour. In contrast, Tetrahymena pyriformis cells that fed on bacteria from FS
      sediment ingested 12.7 bacteria per ciliate and hour. Bacterial abundances in the
      sediment were equal in both sediment types (4 x 10(8) cells g sediment dry
      weight(-1)) when determined by DAPI counts. However, when analyzed using DTAF
      counts, the number of bacteria in the FS-sediment increased to 9.7 x 10(8) cells
      g sediment dry weight(-1). From our findings we conclude that bacterivory by
      ciliates is overestimated when FS-sediment is used because DTAF stains bacteria
      as well as protein-containing detritus particles, which are also ingested by many
      ciliates. In contrast, FISH is a direct, a posteriori method that specifically
      stains phylogenetic lineages, e.g. eubacteria, after ingestion and thereby avoids
      a false determination of the number of ingested bacteria. Thus this method can
      also be used for the study of natural ciliate bacterivory in benthic systems.

PMID- 14666992
TI  - New Penicillium species associated with bulbs and root vegetables.
AB  - Taxa of the Penicillium series Corymbifera are known for their strongly
      fasciculate growth and association with the rhizosphere of vegetables and flower
      bulbs. Using micromorphology, colony characteristics on various media and
      chemotaxonomic profiling, P. albocoremium sensu stricto and two new species, P.
      radicicola and P. tulipae, are redescribed during a taxonomic survey of P.
      albocoremium isolates contained within the IBT culture collection. Although these
      novel taxa are micromorphologically quite similar, their unique secondary
      metabolite profiles individually distinguish them from isolates of P.
      albocoremium. Moreover, the following metabolites produced by these species are
      known mycotoxins: citrinin, penicillic acid and terrestric acid by P. radicicola
      and terrestric acid and penitrem A by P. tulipae.

PMID- 14666993
TI  - Comparative organ system development: continuing the series.

PMID- 14666994
TI  - Postnatal anatomical and functional development of the heart: a species
      comparison.

PMID- 14666995
TI  - Species comparison of anatomical and functional immune system development.
AB  - The components of the immune system have not been traditionally emphasized as
      potential target organs in standard developmental and reproductive toxicity
      (DART) protocols. A number of workshops have been organized in recent years to
      examine scientific questions that underlie developmental immunotoxicity tests,
      and the interpretation of results as they relate to human risk assessment. A key
      question that must be addressed is to determine the most appropriate species and
      strains to model the developing human immune system. The objective of this review
      is to compare the anatomical and functional development of the immune system in
      several species important to either preclinical studies for drug development or
      safety assessments for chemicals, with what is known in humans. The development
      of the immune system in humans will be compared to what is known in mice, rats,
      dogs and nonhuman primates.

PMID- 14666996
TI  - Pretreatment with periodate-oxidized adenosine enhances developmental toxicity of
      inorganic arsenic in mice.
AB  - BACKGROUND: Inorganic arsenic, given by injection to pregnant laboratory animals,
      can induce malformations. Arsenic methylation can be inhibited by periodate
      oxidized adenosine (PAD). Severe human health effects from high chronic arsenic
      exposure have mainly been reported in populations with significant levels of
      malnutrition, which may enhance toxicity by diminishing arsenic methylating
      capacity. This study sought to determine the effect of inhibition of arsenic
      methylation on the developmental toxicity of arsenic in a mammalian model.
      METHODS: PAD (100 microM/kg, i.p.), was given to pregnant CD-1 strain mice 30 min
      before 7.5mg/kg sodium arsenite [As(III)], i.p., or 17.9 mg/kg sodium arsenate
      [As(V)], i.p., on gestation day 8 (GD 8; copulation plug = GD 0). Control dams
      received As(III), As(V), or PAD alone or were untreated. Test dams were killed on
      GD 17, and their litters were examined for mortality and gross and skeletal
      defects. RESULTS: Pretreatment with PAD before either arsenical resulted in
      increased maternal toxicity and lower fetal weights. Pretreatment also caused
      higher prenatal mortality, with 8 of 21 and 5 of 17 litters totally resorbed in
      the PAD plus As(III) and PAD plus As(V) treatment groups, respectively.
      Significant increases in the incidences of exencephaly, ablepharia, and anomalies
      of the vertebral centra, sternebrae, and ribs were also associated with PAD
      pretreatment. Short tail (3 fetuses in 3 litters) was seen only following PAD
      plus As(III) treatment. CONCLUSIONS: These results demonstrate that the
      developmental toxicity of inorganic arsenic can be enhanced by PAD, due possibly
      to inhibited methylation of arsenic.

PMID- 14666997
TI  - Comparison of prostate gene expression and tissue weight changes as monitors of
      antiandrogen activity in GNRH-inhibited rats.
AB  - BACKGROUND: The Hershberger assay for antiandrogens and modifiers of steroid
      biosynthesis uses surgically-castrated rats. We described an adaptation of the
      assay using the GnRH inhibitor Antarelix in place of surgical castration [Ashby
      J, Lefevre PA, Deghenghi R, Wallis N. Regulatory Toxicology and Pharmacology
      34:188-203, 2001], and concomitantly described changes in expression of the
      androgen-dependent prostatic genes PBP C3, TRPM-2, and ODC as a possible
      complement to gravimetric analysis of the sex accessory tissues (SAT) [Nellemann
      C, Vinggaard AM, Dalgaard M, Hossaini A, Larsen J-J. Toxicology 163:29-38, 2001.
      METHODS: The present study describes the results of combining these two
      modifications into a single assay. During the course of these experiments it was
      shown that SD rats gave similar results to AP rats and that the higher
      stimulatory dose of testosterone propionate (TP) used in our experiments gave
      stronger assay responses to FLU than the lower dose of TP used by some earlier
      investigators. The potent antiandrogen flutamide (FLU) and the weak antiandrogen
      DDE were used to evaluate this modified assay. RESULTS: For all parameters
      studied (SAT weights and changes in expression of the 3 prostatic genes) FLU gave
      the expected positive results. The weak antiandrogen DDE gave variable and mainly
      non-reproducible responses. Use of DDE as a weak antiandrogen accelerated
      assessment of the new assay. CONCLUSIONS: Possible reasons for this failure to
      detect DDE are discussed, and it is concluded that the modified assay is
      unsuitable for use in its present form. The use of gene expression analyses
      together with evaluation of SAT weights is a promising tool as an early and
      sensitive marker of antiandrogen action, but more work is needed on the choice of
      time frame as well as the selection of genes to monitor.

PMID- 14666998
TI  - Gastroschisis is caused by the combination of carbon monoxide and protein-zinc
      deficiencies in mice.
AB  - BACKGROUND: Gastroschisis is a rare congenital defect of the abdominal wall. Its
      occurrence is noted primarily in the offspring of young mothers who often smoke
      during pregnancy. The incidence of gastroschisis has been increasing in many
      countries in recent years. The etiology of gastroschisis is not known. METHODS:
      Pregnant mice of CD-1 strain were maintained on 17 and 9% protein diets mixed
      with deficient, normal, or supplemental zinc levels throughout gestation. The
      dams in each protein-zinc diet group were randomly divided in two groups. One
      group was exposed to air (control) and the other to 500 ppm carbon monoxide (CO)
      in air, in environmental chambers, from gestation days (GD) 8-18. The dams were
      sacrificed by carbon dioxide asphyxiation on GD 18, and data on malformations was
      collected. RESULTS: The rates of fetal mortality and malformations were increased
      by protein and zinc deficiencies. Carbon monoxide exposure also increased fetal
      mortality. In the low protein group, the rate of fetal mortality was inversely
      related to the dietary zinc level, and the rate of fetal malformations was
      highest in the zinc deficient group. The incidence of gastroschisis in the low
      protein/zinc deficient/CO exposed group was 47%, and 60% of the litters were
      affected. The incidence of gastroschisis in the rest of the low protein/zinc
      diets/air or CO groups was 0. CONCLUSION: The data indicates that gastroschisis
      is caused by the combination of protein-zinc deficiencies and carbon monoxide
      exposure during gestation. The finding may be relevant to human populations that
      experience protein and zinc deficiencies during gestation, and are exposed to CO
      pollution, or cigarette, or marijuana smoke during pregnancy.

PMID- 14666999
TI  - Effect of feed restriction on Hershberger and pubertal male assay endpoints.
AB  - BACKGROUND: The Hershberger and male pubertal onset assays have been identified
      as possible Tier I screening tests to detect endocrine-active compounds (EACs).
      Both tests rely on changes in reproductive and/or accessory sex gland (ASG)
      weights in young animals. Because chemical treatment may affect growth rate, the
      relationship between body weight and reproductive/ASG weights was examined using
      feed restriction (FR) to produce a targeted 10% decrease in body weight. METHODS:
      In the male pubertal onset assay, 23-day-old rats (12/group) were given ad lib
      feed or FR until euthanized at 45, 49, 52, 56, or 59 days of age. Despite a 10%
      body weight differential, pubertal onset was not significantly delayed and testes
      weights were conserved. Absolute prostate, ventral prostate, seminal vesicle,
      epididymides, and liver weights were decreased by FR. Relative weights for the
      prostate, ventral prostate, and seminal vesicles were similar to controls, but
      relative epididymides and liver weights still exhibited FR-mediated changes. In
      the Hershberger assay, male rats (12/group) castrated at 36 days of age were
      given ad lib feed or FR in the presence or absence of testosterone propionate (T)
      from 46-55, 50-59, or 56-65 days of age. At 56, 60, and 66 days of age, rats were
      euthanized. In untreated animals, FR did not alter absolute ventral prostate,
      seminal vesicles, or Cowper's gland weights; however, absolute and relative
      weights of the levator anibulbocavernosus muscles (LABC) were affected. In T
      treated animals, absolute organ weights (the ventral prostate, seminal vesicles,
      LABC, and glans penis) were relatively insensitive to FR. The weight of the
      Cowper's gland was affected only at 66 days of age. RESULTS: These data show that
      reproductive and ASG organ weight endpoints in the Hershberger and male pubertal
      onset assays can be influenced by FR levels that produce a 10% change in terminal
      body weight. CONCLUSIONS: The establishment of objective criteria for a positive
      or negative result is problematic due to the confounding effects of body weight
      on some endpoints. Furthermore, a 10% decrease in body weight seems to be
      excessive as a requirement for high-dose toxicity in these assays due to possible
      indictment of agents that are not EACs, as well as potential masking of EAC
      effects coincident with body weight changes. Minimally, caution must be used in
      interpreting assay results in the presence of a 10% body weight change,
      recognizing the possible confounding effects of this degree of growth
      suppression.

PMID- 14667000
TI  - Maternal-fetal distribution and prenatal toxicity of 2,2,4-trimethyl-1,2
      dihydroquinoline in the rat.
AB  - BACKGROUND: Polnoks R (poly-2,2,4-trimethyl-1,2-dihydroquinoline) is used as an
      antioxidant in elastomer processing. It is an embryotoxic and fetotoxic agent.
      This chemical given per os to female rats induces also teratogenic effect but
      only at doses toxic to the mother. The aim of the study was to evaluate prenatal
      development and tissue distribution in rats exposed to 2,2,4-trimethyl-1,2
      dihydroquinoline (TMDHQ), a monomer of Polnoks R. METHODS: Females were exposed
      orally to unlabeled TMDHQ during organogenesis at doses 50-400 mg/kg to asses
      prenatal toxicity and to radiolabeled 14C monomer at a dose 210 mg/kg to evaluate
      tissues distribution. RESULTS: TMDHQ administered to pregnant females per os at
      doses 100 mg/kg and higher produced teratogenic effect (cleft palate, wavy ribs,
      kyphoscoliosis, exencephaly, external hydrocephalus, hydronephrosis, and renal
      hypoplasia). Peak 14C-radioactivity was found in mothers' plasma about 10 hr
      after administration of this compound at dose 210 mg/kg. The accretion of 14C
      proceeded with a kinetic constant of 0.35 hr(-1) and a half-life of 53.3 hr.
      Kidneys are the main organs of monomer excretion. The highest concentration of
      14C in maternal tissues 24 hr after oral dosing was found in adipose tissue,
      sciatic nerve, muscles, kidneys, and liver. Radiocarbon retention in fetuses was
      the highest in kidneys at all time points after dosing. CONCLUSIONS: This study
      has demonstrated that transplacental exposure to Polnoks R monomer is teratogenic
      in rats. 14C retention in placenta, amniotic fluid, and fetal tissues indicates
      that this compound or its metabolites penetrate into placenta to the fetus.

PMID- 14667001
TI  - Effects of gestational exposure to ethane dimethanesulfonate in CD-1 mice:
      microtia and preliminary hearing tests.
AB  - BACKGROUND: Microtia is a reduction in pinna size, usually seen in humans in
      conjunction with other medical conditions. We report microtia in CD-1 mice after
      gestational exposure to ethane dimethanesulfonate (EDS), an alkylating agent and
      adult rat Leydig cell toxicant. METHODS: Time-pregnant CD-1 mice were
      administered 0, 80, or 160 mg EDS/kg on gestation days (GD) 11-17, or 0 or 160 mg
      EDS/kg on GD 11-13, GD 13-15 or GD 15-17. Pinnae were measured on postnatal days
      (PND) 4, 8, 18, and 28; and were observed for detachment from birth through PND
      8. Branchial-arch derived skeletal structures and histology of the pinna was
      examined on PND 4 and 24. Brainstem auditory evoked response (BAER) tests were
      carried out at approximately PND 160 to determine possible effects on hearing.
      RESULTS: All offspring of EDS-treated dams exhibited bilateral, dose-related
      decreases in pinna size. Gestational exposure during GD 11-13 produced smaller
      ears than during GD 13-15 or 15-17, but not as small as the GD 11-17 regimen.
      Ossification of other pharyngeal arch derivatives was delayed whereas histology
      was unremarkable. BAER analysis showed a decrease in the proportion of adult
      offspring producing a quantifiable response to varied auditory stimuli among EDS
      treated litters. CONCLUSIONS: Gestational exposure to EDS affects pinna
      development in the mouse, with a broad period of sensitivity during the second
      half of gestation. Microtia induced by EDS may be associated with hearing
      deficits, suggesting functional importance of pinna size or additional effects of
      EDS on ear development not detected by morphological examination.

PMID- 14667002
TI  - Gender differences in burnout among Dutch dentists.
AB  - OBJECTIVES: Differences between the sexes in the manifestation of burnout have
      been reported for different occupational groups. Although some gender-specific
      explanations for this finding have been forwarded, there is a paucity of studies
      in which the relation with other work-related gender differences is examined. The
      objective of this study was to analyze gender differences in burnout among
      dentists and to identify possible concomitant factors. METHODS: Male (n = 411)
      and female (n = 81) Dutch dentists filled out the Dutch version of the Maslach
      Burnout Inventory (MBI) together with several health and work-related
      questionnaires. RESULTS: Results showed male dentists to report a higher score on
      the depersonalization dimension of the MBI than did female dentists. No gender
      differences were found on the other dimensions (i.e. emotional exhaustion and
      personal accomplishment). Moreover, no gender-related differences in experienced
      work-stress or health-related aspects were found. It was found, however, that
      male dentists put in working hours and see more patients per week when compared
      to female dentists. Also, a difference in mean age was found. Our main finding
      was that the difference in depersonalization disappears when controlling for
      working hours and age. CONCLUSIONS: Gender differences in burnout among dentists
      do exist. However, our results indicate that underlying factors, such as working
      hours, have a profound effect on these differences. These results can have direct
      practical consequences, for instance, in distinguishing between groups concerning
      the way burnout scores should be interpreted.

PMID- 14667003
TI  - Chewing ability of subjects with shortened dental arches.
AB  - OBJECTIVES: The objective was to study chewing ability in subjects with shortened
      dental arches in Tanzania. METHODS: A sample of 725 adults with shortened dental
      arches comprising intact anterior regions and 0-8 occluding pairs of posterior
      teeth and 125 adults with complete dental arches were recruited. Subjects were
      classified into nine categories according to arch length and symmetry. Chewing
      ability was investigated by interview on chewing complaints and on perceived
      difficulty of chewing 20 common Tanzanian foods, 12 soft, and 8 hard. RESULTS:
      Categories with extreme shortened arches (0-2 pairs of occluding premolars)
      reported most frequent (95-98%) and most severe complaints ('cannot chew all
      foods' or 'have to use special or specially prepared food'). Categories with
      intact premolar regions and at least one occluding pair of molars had nearly no
      complaints (95-97%). The other arch categories had an intermediate volume of
      complaints (33-54%). Perceived difficulty of chewing deteriorated with a decrease
      of occluding pairs of teeth. Subjects with 0-2 pairs of occluding premolars had
      major difficulties with chewing. Subjects with 3-4 pairs of occluding premolars
      or asymmetric arches comprising a short side with none or one pair of premolars
      and a long side including at least one occluding pair of molars had more
      difficulties with chewing compared to subjects with more complete dental arches.
      As a whole, they perceived for hard foods, 'minor problems, not adapted'.
      CONCLUSIONS: Shortened dental arches with intact premolar regions and at least
      one occluding pair of molars provide sufficient chewing ability. Shortened arches
      with 3-4 pairs of occluding premolars and asymmetric arches with a long side
      result in impairment of chewing ability, especially for hard foods. In extremely
      shortened arches comprising 0-2 occluding premolars, chewing ability is severely
      impaired.

PMID- 14667004
TI  - Agreement between mothers and children aged 11-14 years in rating child oral
      health-related quality of life.
AB  - OBJECTIVES: To assess the agreement between mothers and children concerning the
      child's oral health-related quality of life. METHODS: A total of 42 pairs of
      mothers and children aged 11-14 years with oral and orofacial conditions
      completed the parental (PPQ) and child (CPQ(11-4)) components of the Child Oral
      Health Quality of Life Questionnaire. The PPQ and CPQ(11-14) are analogous
      questionnaires with 31 common items. Agreement between overall and subscale
      scores derived from the questionnaires were assessed in comparison and in
      correlation analyses. The former used mean directional differences between
      mothers and children to assess bias and mean absolute differences to assess
      agreement at the group level. The latter used intraclass correlation coefficients
      (ICCs) to assess agreement at the level of individual mother-child pairs.
      RESULTS: At the group level, agreement between mothers and children was good.
      There was little evidence of bias in mothers' reports compared to those of their
      children. The mean absolute difference in overall scores constituted 9% of the
      possible range of scores. However, the significance of this difference is
      difficult to interpret. The ICC for overall scores was 0.70 indicating
      substantial agreement between mother and child pairs. However, the ICCs for the
      emotional and social well-being subscales indicated moderate agreement only.
      There was a suggestion that the level of agreement varied according to the
      characteristics of the child. CONCLUSION: Although mothers may be used as proxies
      for their children in some circumstances and for some purposes, the views of both
      should be obtained in order to fully represent child oral health-related quality
      of life.

PMID- 14667005
TI  - Time and duration of eruption of first and second permanent molars: a
      longitudinal investigation.
AB  - OBJECTIVE: The aim of this study was to investigate the variation in (i) the time
      (age) of eruption and (ii) the duration of the eruption of first (M1) and second
      (M2) permanent molar teeth. Finally, the study also provides data about the
      association between time of eruption of the first of the M1s and the first of the
      M2s. METHODS: The study was carried out in Nexo Public Dental Health Service,
      Denmark. All children who, in a period of 12 months, had the first of their M1s
      or M2s recorded as erupted and the occlusal surface still partly covered by
      gingiva formed the study groups (N = 69 and 112 children, respectively). The
      continued eruption of all four molar teeth was recorded at recall intervals not
      exceeding 4 months until functional occlusion was obtained. RESULTS: First
      permanent molars: eruption time--girls: from the age of 5 years and 3 months to 7
      years and 8 months (mean 6.1 years); boys: from 5 years and 2 months to 7 years
      and 10 months (mean 6.3 years). The duration of eruption--girls: from 5 to 32
      months (mean 15.4 months); boys: from 7 to 28 months (mean 15.0). Second
      permanent molars: eruption time--girls: from the age of 8 years and 11 months to
      14 years and 4 months (mean 11.3 years); boys: from 9 years and 11 months to 13
      years and 11 months (mean 12.0 years). The duration of eruption--girls: from 12
      to 44 months (mean 27.1 months); boys: from 9 to 45 months (mean 27.9 months). No
      correlation was found between the time of eruption and the duration of eruption
      of M1 or M2. There was a strong positive association between the time of eruption
      of the M1s and the M2s (r(s) = 0.81). CONCLUSIONS: A tremendous variation was
      found in time of eruption and in duration of eruption of permanent molars. This
      variation highlights the importance of individualizing caries preventive
      strategies for children.

PMID- 14667006
TI  - Relationship of dental status, sociodemographic status, and oral symptoms to
      perceived need for dental care.
AB  - OBJECTIVE: Previous studies have noted a discrepancy between clinically
      determined oral health status (normative need), patients' perceptions, and
      perceived significance of dental signs and symptoms. Our objective was to
      quantify the relationships between normative need and self-reports to improve our
      understanding of the factors that contribute to perceived need for care. METHODS:
      Clinical examination and questionnaire data were derived from the Florida Dental
      Care Study, a study of oral health and dental care, in a representative sample of
      community-dwelling adults aged > or = 45 years. The questionnaire provided
      information about presence of signs and symptoms, self-ratings of oral health,
      perceived need for dental care, and sociodemographic status (SDS). Perceived need
      was measured on a 4-point nominal scale. RESULTS: Self-reported broken filling,
      broken denture, cavities, loose tooth, teeth that look bad, and toothache were
      strongly associated with self-reported perceived need for dental care.
      Satisfaction with dental health was also associated with perceived need, but self
      rated oral health was not. Most measures of SDS were associated with perceived
      need. However, in a single multiple regression, with self-reported signs and
      symptoms accounted for, race, age group, sex, and educational attainment were not
      significantly associated with a currently perceived dental problem. CONCLUSIONS:
      Certain dental signs and symptoms were significantly associated with perceived
      need for dental care, as were certain aspects of SDS; even once differences in
      dental signs and symptoms had been taken into account. Disaggregating measurement
      of perceived need from a single dichotomous ('yes/no') scale to a 4-point nominal
      scale was elucidative.

PMID- 14667007
TI  - Caries incidence rates in Swedish adolescents and young adults with particular
      reference to adjacent approximal tooth surfaces: a methodological study.
AB  - OBJECTIVES: The objective was to assess the dependence of the caries status of
      the adjacent approximal surface on the incidence of approximal caries. METHODS:
      At baseline, the material consisted of a cohort of 536 Swedish children. The
      individuals were followed through annual bitewing radiographs from the age of 11
      13 to 21-22 years. A radiographic scoring system was used to assess the caries
      status of the surfaces: scores 0 and 1 = sound surface to score 4 = caries in the
      outer half of the dentine. A model was used to calculate the dependence of the
      caries status of adjacent approximal tooth surfaces. The unit of analysis was a
      pair of adjacent approximal surfaces and in all, 12 pairs of posterior approximal
      surfaces were analysed. RESULTS: The individual caries rates of the 24 posterior
      approximal surfaces ranged from 1.3 to 8.3 new caries lesions per 100 tooth
      surface-years. The caries rate of an approximal tooth surface depended on the
      caries status of the adjacent surface: a sound surface next to a sound surface
      had a relatively small risk of developing caries, while the risk increased 1.6
      32.3 times if the adjacent surface was in a caries state as judged
      radiographically. The distal surface of the first molar developed caries more
      often than the mesial surface of the second molar. CONCLUSIONS: The caries rate
      of an approximal tooth surface was 1.6-32.3 times higher if the adjacent surface
      was in a caries state compared to when the latter was sound.

PMID- 14667008
TI  - Patient participation during dental consultations: the influence of patients'
      characteristics and dentists' behavior.
AB  - OBJECTIVE: This study examined the influence of the following variables on
      patients' information-seeking and participating behavior during emergency
      treatment: patients' preferences for information and participation, patients'
      coping style, patients' socio-demographic variables, and dentists' communicative
      behavior. METHODS: The sample consisted of 83 patients receiving emergency care
      from 13 different dentists. Consultations were videotaped in order to assess
      dentists' and patients' behavior. Dentists' communicative behavior was coded by
      means of the Communication in Dental Settings Scale (CDSS); scores for patients'
      behavior included the number and nature of questions asked during the
      consultation, attempts to offer diagnoses, and whether or not patients made the
      decision to undergo treatment themselves. At home, patients filled out a
      questionnaire that included scales to measure their preference for information
      and participation and other background variables. RESULTS: Results showed that
      patients' desire for information and participation, together with other
      variables, was not reflected in their overt behavior. Furthermore, dentists'
      communicative behavior was unrelated to patients' information-seeking and
      participating behavior. CONCLUSIONS: Scores on the CDSS show that still there is
      a discrepancy between the legal prerequisites of information-giving and emergency
      dental practice. Therefore, dentists' information-giving behavior should be
      improved in order to enhance the patients' right to make informed decisions.

PMID- 14667009
TI  - Tobacco prevention in Swedish dental care.
AB  - OBJECTIVE: To assess tobacco prevention in Swedish dental care and to identify
      barriers. Also, to investigate whether dentists and dental hygienists were
      familiar with recently published review of smoking cessation methods. METHODS: A
      questionnaire was mailed to all 353 dental hygienists and 528 dentists in
      Stockholm County. RESULTS: The overall response rate was 61% for the dentists and
      67% for the dental hygienists. Nearly all considered smoking to be a major health
      issue, but one out of two was not convinced that smokeless tobacco use was a
      major health problem. A small minority was routinely engaged in cessation
      support. However, on the aggregate level, the active dentists and hygienists
      advised annually approximately 70 000 and 40 000 smokers, respectively. The main
      barrier to cessation counseling was lack of smoking cessation experts to refer to
      and was followed by a lack of reimbursement, a lack of knowledge, time
      constraints, and a feeling of inadequacy. Also, one out of two dentists and 3 out
      of 10 hygienists did not see it as a part of their job to help patients stop
      smoking. Approximately 10% in both groups made use of the review of smoking
      cessation methods. Fifty per cent of these had increased their cessation
      consultations by an average of 30% because of the guidelines. On the average,
      dentists and hygienists had spent approximately 1.4 and 2.9 h, respectively,
      during the previous month on all smoking cessation activities. CONCLUSIONS:
      Despite several barriers, there is an excellent potential for a more active role
      in tobacco cessation counseling in Swedish dental care.

PMID- 14667010
TI  - A 5-year evaluation of two glass-ionomer cements used as fissure sealants.
AB  - OBJECTIVE: To evaluate the retention and caries preventive effect of two glass
      ionomers used as fissure sealants: one resin modified glass ionomer (A) and one
      conventional glass-ionomer cement (B). SAMPLES AND METHODS: The permanent first
      molars of 100 children, 6-8 years of age at the start of the study, were sealed.
      Material A was applied on one side (right side, upper, and lower) and material B
      was applied on the contralateral side (left side, upper, and lower) of the mouth.
      The control group was composed of 108 children who did not receive fissure
      sealant but received oral health education. After 5 years, 64.0% of the children
      of the experimental group and 73.0% of the children of the control group were
      available for reexamination. RESULTS: Material A was completely lost in 74.2% and
      material B in 89.0% (Wilcoxon matched pairs test, P < 0.05). Total retention rate
      was 1.6% for materials A and B. After 5 years, caries increment was 21.5% for the
      experimental group and 34.2% for the control group (chi2-test, P < 0.05).
      CONCLUSION: Sealing pits and fissures with glass-ionomer cements was effective in
      preventing caries.

PMID- 14667011
TI  - An oral health promotion program for an urban minority population of preschool
      children.
AB  - The objective of this project was to design, implement and evaluate an oral
      health promotion program for inner-city Vietnamese preschool children in
      Vancouver, British Columbia, Canada. The project comprised of four general
      phases: information-gathering, project planning, project implementation, and
      project evaluation. The information-gathering phase of the project demonstrated
      extensive tooth decay in young children, bottle use during the day and during
      sleep-time long past recommended weaning age, and a belief of many parents that
      primary teeth were not important. Based on this information, the project planning
      committee designed a program that featured one-to-one counseling supported by
      community-wide activities. A Vietnamese lay health counselor provided counseling
      to mothers with telephone follow-up that coincided with scheduled infant
      immunization visits to a twice-monthly Child Health Clinic for Vietnamese
      families. At all the follow-up assessment clinics scheduled over the 7-year
      duration of this continuing project, mothers who had had more than one counseling
      visit reported significantly less use of sleep-time and daytime bottles for their
      children, and their children demonstrated significantly reduced prevalence of
      caries compared to similarly aged children at baseline. One-to-one counseling
      with regular follow-up provided by a lay person of similar background and culture
      to the participants is an effective way to facilitate adoption of healthy
      behaviors and to improve oral health of children.

PMID- 14667012
TI  - Conceptual foundations for infectious disease surveillance.
AB  - The purpose of this report is to offer concepts for consideration in developing
      infectious disease surveillance systems, defined here as active, formal, and
      systematic processes intentionally directed to rapidly seek out and identify
      infectious disease agents or disease. Performance of surveillance systems can be
      judged by their accuracy (sensitivity and specificity), precision
      (repeatability), timeliness, multiple utility, and value. Surveillance system
      operation and function necessary to achieve high performance are defined in part
      by characteristics of the specific infectious disease, including disease
      transition state dynamics, that define probabilities of being in the latent,
      infectious, or clinical phase of disease. Two key components of surveillance are
      the sampling scheme, which is intended to maximize the probability of capturing
      an infected animal or specimen as soon as possible after the herd has been
      exposed, and the diagnostic assays, which should maximize the probability of
      detecting the agent, or evidence of the agent, if it is present in the specimen,
      while minimizing the likelihood of a false-positive result. Proportional risk
      sampling, targeted sampling, and repeated sampling are strategies that can
      improve overall surveillance system accuracy and particularly the temporal
      sensitivity related to early detection. Hierarchical sampling schemes and
      multiplexed assays can maximize efficiency and improve utility by serving
      multiple surveillance systems and purposes. Development of the surveillance
      systems needed to address emerging and foreign animal diseases will necessarily
      require design and architecture that are highly probability-driven to maximize
      surveillance sensitivity and specificity and to minimize cost.

PMID- 14667013
TI  - Uterine neoplasia in 13 cats.
AB  - Thirteen uterine tumors were diagnosed in 13 cats and accounted for 0.29% of all
      feline neoplasms received during a 9.6-year period. Age at diagnosis ranged from
      3 to 16 years; median 9 years. Six were Domestic Shorthair cats, and 7 were
      purebred cats of 5 different breeds. Eight adenocarcinomas and 1 mixed Mullerian
      tumor (adenosarcoma) comprised the endometrial tumors. Myometrial tumors included
      3 leiomyomas and 1 leiomyosarcoma. One of the adenocarcinomas developed in the
      uterine stump of an ovariohysterectomized cat; the other cats were sexually
      intact. Concurrent mammary adenocarcinoma was diagnosed in 1 cat with uterine
      adenocarcinoma and in another with uterine leiomyoma. Tumors were discovered
      during elective ovariohysterectomy in 2 cats, but at least 3 others had
      experienced reproductive problems (infertility or pyometra). Five cats presented
      for abdominal or pelvic masses. Endometrial adenocarcinomas were positive
      immunohistochemically for cytokeratins and negative for smooth muscle actin
      (SMA): 1 of 6 cats was positive for vimentin and 4 of 8 were positive for
      estrogen receptor-alpha (ER alpha). Adenosarcoma stromal cells were positive for
      vimentin and ER alpha but negative for cytokeratins and SMA. Smooth muscle tumors
      were positive for vimentin and SMA and negative for cytokeratins. Leiomyomas, but
      not the leiomyosarcomas, were positive for ER alpha. Adenocarcinomas in 4 cats
      had metastasized by the time of ovariohysterectomy. Two other cats were
      euthanized 5 months after ovariohysterectomy; at least one of these cats had
      developed an abdominal mass that was not examined histologically. Only 2 cats
      with endometrial adenocarcinoma had disease-free intervals longer than 5 months
      after surgery. Metastasis was not detected in any mesenchymal tumor; however,
      these cats were either euthanized on discovery of the tumor or the tumor was
      first detected at necropsy.

PMID- 14667014
TI  - Determination of the median toxic dose of type C botulinum toxin in lactating
      dairy cows.
AB  - Because of the difficulty in identifying botulinum toxin in cattle, it is
      hypothesized that cattle are sensitive to levels of toxin below the detection
      limits of current diagnostic techniques (the mouse protection bioassay and the
      immunostick enzyme-linked immunosorbent assay [ELISA] for type C botulinum
      toxin). Using an up-down method for toxicologic testing, the median toxic dose
      (MTD50) for cattle was determined. Four lactating Holstein cows were dosed at
      0.125 or 0.25 ng/kg with Clostridium botulinum type C toxin and failed to develop
      clinical signs of botulism during the 7-day observation period. Three cows given
      0.50 ng/kg of toxin developed clinical signs of botulism. From these results, the
      MTD50 was calculated at 0.388 ng/kg (3.88 mouse lethal doses/kg) using the trim
      logit method. These results suggest that cattle are 12.88 times more sensitive to
      type C botulinum toxin than a mouse on a per kilogram weight basis. The mouse
      protection bioassay and the immunostick ELISA for type C botulinum toxin failed
      to identify the presence of the toxin in the serum, blood, and milk samples taken
      from all 7 animals.

PMID- 14667015
TI  - Molecular detection of Anaplasma platys in dogs using polymerase chain reaction
      and reverse line blot hybridization.
AB  - Several polymerase chain reactions (PCRs) and a reverse line blot hybridization
      (RLB) method were used to identify Anaplasma platys in dogs held in a kennel in
      Italy. Whereas PCR techniques confirmed the presence of A. platys, the RLB method
      not only correlated the results obtained by PCR but also ruled out the presence
      of other species such as Ehrlichia canis or E. chaffeensis. There was no
      correlation between infection status and age or breed of the dogs. Polymerase
      chain reaction performed on the Rhipicephalus sanguineus ticks collected from
      those dogs showed that they were also infected with A. platys. Sequences obtained
      from some samples and compared with those within the GenBank also confirmed the
      presence of A. platys.

PMID- 14667016
TI  - Short-term repeatability of measurements of antimicrobial susceptibility of
      Escherichia coli isolated from feces of feedlot cattle.
AB  - Short-term stability of measurements of antimicrobial susceptibility of
      Escherichia coli isolated from feces of feedlot cattle is important in developing
      monitoring and surveillance programs. Frequent evaluations (i.e., daily) are
      resource intensive and in some situations may be impractical for long-term
      sampling protocols. Consequently, a point-in-time measurement will need to be
      used to represent conditions in the perisampling period. In this study, 30 fecal
      samples were collected from each of 6 cattle pens on a commercial cattle feedlot
      on 2 occasions separated by 48 hours. Escherichia coli was isolated from single
      and pooled samples. The isolates were tested for antimicrobial susceptibility
      against a panel of 17 antimicrobials. Resistance to 5 antimicrobials (ampicillin,
      nalidixic acid, streptomycin, sulfamethoxazole, and tetracycline) was detected in
      single and pooled samples from both sampling periods (days 1 and 3). The
      prevalence of isolates resistant to these 5 antimicrobials was 2% or higher in
      all treatment combinations except for pools obtained from day 3 samples. Lower
      levels of resistance to 6 more antimicrobials were detected inconsistently across
      the single and pooled samples. Logistic models constructed for the antimicrobials
      to which the E. coli isolates were most commonly resistant demonstrated that
      there were no significant differences between periods (P > 0.10) and between
      single and pooled samples (P > 0.20). The distribution of the number of
      antimicrobials to which isolates were resistant was consistent for the single
      samples across periods, but there appeared to be a lower prevalence of any
      resistance in day 1 pooled samples. A larger number of resistant phenotypes were
      detected in the single samples than in the pooled samples, and resistant
      phenotypes with prevalence of less than 2% were detected inconsistently across
      periods and single and pooled samples. Resistance to individual antimicrobials
      was consistent by all measures when the prevalence was at least 2%. Inconsistent
      results were obtained for antimicrobials to which resistance rarely occurred. The
      apparent inconsistencies do not appear to be related to external factors but
      rather to sampling intensity. Short-term stability is a plausible assumption
      under sampling strategies that are designed to detect specific levels of
      prevalence. However, when resistance levels fall below these levels, there will
      likely be fluctuations in the presence or absence of rare resistant phenotypes
      and in their prevalence and central tendency measures.

PMID- 14667017
TI  - Detection of Escherichia coli O157:H7 in cattle feces using a polymerase chain
      reaction-based fluorogenic 5' nuclease (TaqMan) detection assay after secondary
      enrichment.
AB  - Currently, methods for recovering and identifying Escherichia coli O157:H7 from
      cattle feces are inconsistent and hindered by their inability to specifically and
      rapidly detect small numbers of organisms from this complex and highly variable
      matrix. A standard approach for isolating and characterizing E. coli O157:H7 from
      cattle feces was compared with a polymerase chain reaction (PCR)-based 5'
      nuclease assay specific for E. coli O157:H7 that included a secondary enrichment
      step. The PCR-based method proved a better indicator of the presence of the
      organism than the culture procedure. Retests indicated that the inclusion of a
      secondary enrichment step and the subsequent analysis by the 5' nuclease assay
      were reproducible and specific. Escherichia coli O157:H7 could be detected in
      fecal samples that were otherwise negative after a primary enrichment step,
      immunomagnetic separation, and plating onto sorbitol MacConkey agar plates
      containing cefixime and tellurite (CT-SMAC). In samples that were initially
      identified as culture positive but PCR negative, retesting of the culture
      isolates on CT-SMAC indicated that the sorbitol fermentation interpretations
      could frequently not be repeated in retests, whereas retesting using the 5'
      nuclease assay on the original samples demonstrated a high level of agreement
      with the initial PCR conclusions. These results indicate the necessity of
      confirmatory evaluation of isolates culturally recovered by standard cultural
      methods that involve the interpretation of CT-SMAC. The high level of
      disagreement between initial culture results and retests, and the high level of
      agreement between initial PCR results and retests, indicates the advantages of a
      gene-based detection system for identifying E. coli O157:H7 in cattle feces.
      Screening large numbers of fecal samples for E. coli O157:H7 would appear to be
      feasible by integrating the use of enrichment media in serial rounds of
      incubation with a PCR-based fluorogenic detection procedure in high throughput
      detection systems that had automated liquid-handling capabilities.

PMID- 14667018
TI  - Reproduction of postweaning multisystemic wasting syndrome in pigs experimentally
      inoculated with a Swedish porcine circovirus 2 isolate.
AB  - In recent years, porcine circovirus type 2 (PCV2)-associated postweaning
      multisystemic wasting syndrome (PMWS) has been reported worldwide. However, to
      date, PMWS has not been reported in Sweden despite the demonstration of serum
      antibodies to a PCV2-like virus in Swedish pigs. This communication reports the
      experimental reproduction of clinical PMWS after inoculation of colostrum
      deprived (CD) pigs, derived from a Northern Ireland herd, with an isolate of PCV2
      virus recovered from a clinically normal Swedish pig that was necropsied in 1993.
      The clinical disease and histological lesions observed in CD pigs inoculated with
      this virus were indistinguishable from those observed in previous studies on CD
      pigs inoculated with a PCV2 virus isolate recovered from pigs with PMWS. These
      results highlight the disease potential of PCV2 isolated from regions apparently
      free of PMWS and suggest that the status of the host and its environment is an
      important factor in the development of clinical PMWS.

PMID- 14667019
TI  - A single-tube multiplex reverse transcription-polymerase chain reaction for
      detection and differentiation of vesicular stomatitis Indiana 1 and New Jersey
      viruses in insects.
AB  - A multiplex single-tube reverse transcription-polymerase chain reaction (RT-PCR)
      has been developed for the detection and differentiation of vesicular stomatitis
      viruses (VSV), Indiana 1 and New Jersey, from insect samples. Using this assay,
      detection of either or both viruses in as little as 20 fg of total RNA from
      tissue culture was achieved, along with detection of vesicular stomatitis (VS)
      RNA from macerates containing 2 infected mosquitoes in pools of 10-30 noninfected
      mosquitoes. Vesicular stomatitis virus was detected by RT-PCR in all culture
      positive samples, and detection as low as 4 plaque forming units per milliliter
      was achieved. Comparison between RT-PCR and tissue culture revealed that RT-PCR
      was able to detect VSV in a volume of insect macerate averaging almost 100 times
      less than that required for detection by tissue culture. The reported RT-PCR is a
      potential valuable tool for rapid and sensitive detection and differentiation of
      VS in insects because intense work associated with viral isolation, the
      cytotoxicity of insect extracts, and separate virus identification steps can be
      avoided. Potential application to detection and differentiation of VSV serotypes
      from vertebrate hosts is addressed.

PMID- 14667020
TI  - Results of a new serologic test suggest an association of Waddlia chondrophila
      with bovine abortion.
AB  - Waddlia chondrophila is a little-known intracellular organism belonging to the
      order Chlamydiales that has twice been isolated from aborted bovine fetuses. To
      initiate an investigation of the possibility that W. chondrophila may be an
      abortifacient pathogen, a serologic test was developed and used to screen bovine
      sera that were submitted to the Washington Animal Disease Diagnostic Laboratory
      (Pullman, WA). A highly significant statistical association (P < 0.00001) was
      observed when comparing antibody titers in cows that had aborted with those in
      other classes of cattle. Although this result is consistent with the possibility
      that infection with W. chondrophila may be a cause of bovine abortion, it is also
      possible that seroprevalence simply increases with age or that exposure rates
      differ between cows and other classes of cattle. Future serologic studies should
      specifically compare antibody titers between aborting cows and carefully matched
      nonaborting cohorts.

PMID- 14667021
TI  - Molecular and antigenic characterization of Bordetella bronchiseptica isolated
      from a wild southern sea otter (Enhydra lutris nereis) with severe suppurative
      bronchopneumonia.
AB  - Bordetella bronchiseptica was isolated in pure culture from the lung, abdomen,
      and intestine of a wild free-ranging southern sea otter (Enhydra lutris nereis)
      with severe, suppurative bronchopneumonia. Immunohistochemistry, using antiserum
      raised to B. bronchiseptica, revealed strong positive staining of bacteria
      attached to bronchial ciliated epithelia as well as scattered positive staining
      in affected alveoli. Western blot analysis demonstrated that virulence factors,
      filamentous hemagglutinin, pertactin, and adenylate cyclase toxin are produced by
      the sea otter B. bronchiseptica isolate. Ribotype analysis using Pvu II
      restriction digests indicated that this isolate is most similar to strains
      commonly obtained in domestic dogs and cats.

PMID- 14667022
TI  - A case of yellow fever in a brown howler (Alouatta fusca) in Southern Brazil.
AB  - Many brown howlers (Alouatta fusca) have died in a 3-month period in a
      subtropical forest in Southern Brazil. One was examined after a systemic illness.
      According to clinical signs, and necropsy and histopathology findings, yellow
      fever virus (YFV) infection was suspected. Tissue sections from liver, kidney,
      and lymphoid organs were screened by immunohistochemistry for YFV antigens. Cells
      within those tissues stained positively with a polyclonal antibody against YFV
      antigens (1:1,600 dilution), and yellow fever was diagnosed for the first time in
      the brown howler in the area.

PMID- 14667023
TI  - In vitro evaluation of the susceptibility of Edwardsiella ictaluri, etiological
      agent of enteric septicemia in channel catfish, Ictalurus punctatus (Rafinesque),
      to florfenicol.
AB  - In vitro studies were conducted to assess the sensitivity of Edwardsiella
      ictaluri, the etiological agent of enteric septicemia of catfish (ESC), to the
      antibacterial drug florfenicol (FFC). Twelve different E. ictaluri isolates from
      cases submitted between 1994 and 1997 to the Thad Cochran National Warmwater
      Aquaculture Center fish diagnostic laboratory (Stoneville, MS) were used for
      testing. These isolates originated from channel catfish (Ictalurus punctatus)
      infected with E. ictaluri through natural outbreaks of ESC in the commercial
      catfish ponds in Mississippi. Seven hundred sixty-seven additional cultures of E.
      ictaluri were obtained from channel catfish infected experimentally with E.
      ictaluri. In some of these experimental infections, FFC was used for treatment.
      These cultures of E. ictaluri were identified by morphological and biochemical
      tests. Kirby-Bauer zones of inhibition (in mm) for FFC against E. ictaluri were
      determined using standard methods. The minimum inhibitory concentration (MIC) of
      FFC was determined for the natural outbreak E. ictaluri isolates and arbitrarily
      selected experimental cultures. The zones of inhibition for FFC tested with E.
      ictaluri ranged from 31 to 51 mm. The MIC for FFC tested with E. ictaluri was
      consistently 0.25 microg/ml. Edwardsiella ictaluri tested in these studies were
      highly sensitive to FFC in vitro.

PMID- 14667024
TI  - Detection of Tritrichomonas foetus by polymerase chain reaction in cultured
      isolates, cervicovaginal mucus, and formalin-fixed tissues from infected heifers
      and fetuses.
AB  - A rapid, reliable polymerase chain reaction (PCR) assay, originally developed for
      definitive laboratory identification of the bovine venereal pathogen
      Tritrichomonas foetus from cultures of male reproductive tract fluids, was used
      for testing the following: 1) cultured, geographically disparate trichomonad
      isolates, 2) formalin-fixed tissues from infected heifers and naturally infected
      fetuses, and 3) cervicovaginal mucus (CVM) from experimentally infected females.
      In 12 of 12 Western Hemisphere isolates of pathogenic T. foetus (isolated from
      outbreaks of clinical trichomoniasis or from screening surveys) and in 1 of 1
      American Type Culture Collection strain of Tritrichomonas suis, PCR yielded a
      positive result, i.e., a 347-base pair amplicon in the 5.8S ribosomal RNA and
      internal transcribed spacer (5.8S-ITS) region of the genome, whereas cultures of
      Trichomonas vaginalis and Trichomonas gallinae did not produce a PCR product. The
      PCR assay was also positive in formalin-fixed, paraffin-embedded endometrial
      samples from 4 of 4 experimentally infected heifers, as well as in archived
      tissues from 2 of 2 T. foetus-infected aborted bovine fetuses that were submitted
      to the diagnostic laboratory from a natural outbreak. It was negative in fixed,
      embedded uterine tissues of 2 of 2 uninfected virgin heifers used as negative
      controls and in archived fixed gut tissue of a T. gallinae-infected pigeon. In
      another experiment, CVM aspirated from 4 of 4 experimentally infected heifers in
      the fifth or sixth postinfection week yielded a positive PCR product of the
      expected size, whereas CVM from 2 of 2 controls were PCR negative. Pending
      validation in larger clinical studies, the PCR assay for the 5.8S-ITS coding
      region of the T. foetus genome offers the prospect of definitive identification
      of this agent directly from CVM or from formalin-fixed tissues or when false
      positive culture results are suspected.

PMID- 14667025
TI  - Establishment of proliferative cell nuclear antigen gene as an internal reference
      gene for polymerase chain reaction of a wide range of archival and fresh
      mammalian tissues.
AB  - Polymerase chain reaction (PCR) from paraffin-embedded tissues provides a
      powerful tool to amplify DNA from a variety of recent and archival material.
      Because DNA from paraffin-embedded samples is more degraded than from fresh
      material, the amplification of reference genes is essential to exclude false
      negative results. This study describes the use of the proliferative cell nuclear
      antigen (PCNA) gene as a reference gene in a range of animal species and in
      humans. The PCNA-PCR to amplify a fragment extending from exon 5 through exon 6
      and including the intervening intron 6 gave a reproducible pattern, with a 280
      base pair (bp) band from canine, equine, bovine, ovine, and caprine samples
      showing high sequence homology. Porcine, guinea pig, tiger, and lion samples,
      however, gave an additional fragment of approximately 197 bp. The whole intron 6
      from these fragments is missing, possibly representing a pseudogene. In feline
      samples only the 197-bp fragment could be detected. This study shows that the
      PCNA gene is highly conserved across a broad range of animal species and is well
      suited as an internal control for PCR analysis in veterinary medicine.

PMID- 14667026
TI  - Heparin in vitro sensitivity of the activated partial thromboplastin time in
      canine plasma depends on reagent.
AB  - The in vitro heparin sensitivity of 6 different commercial activated partial
      thromboplastin time (APTT) reagents was investigated based on artificial plasma
      samples prepared by addition of sodium heparin at different activities (0-1.5
      IU/ml) to pooled normal canine plasma. Statistical analysis using 2-way analysis
      of variance was based on APTT ratios (APTT/mean APTT control). Significant
      differences between the APTT ratios of different APTT reagents (P < 0.00001) were
      found, which also depended on heparin activity (interaction between the factors;
      P < 0.00001). For example, mean APTT ratio at 0.7 IU/ml heparin varied between
      1.2 and 2.5. The results of this study indicate that recommendations for the
      control of heparin therapy in dogs by APTT ratio should be reagent specific.

PMID- 14667027
TI  - A reverse transcriptase-polymerase chain reaction assay for the diagnosis of
      turkey coronavirus infection.
AB  - This study reports on the development of a reverse transcriptase-polymerase chain
      reaction (RT-PCR) for the specific detection of turkey coronavirus (TCoV). Of the
      several sets of primers tested, 1 set of primers derived from the P gene and 2
      sets derived from the N gene of TCoV could amplify the TCoV genome in the
      infected samples. The RT-PCR was sensitive and specific for TCoV and did not
      amplify other avian RNA and DNA viruses tested except the infectious bronchitis
      virus (IBV). To overcome the problem of IBV amplification, a set of separate
      primers was designed from the spike protein gene of IBV. The RT-PCR under the
      same conditions as above could effectively differentiate between TCoV and IBV.
      The closely related bovine coronavirus and transmissible gastroenteritis virus of
      pigs were differentiated from TCoV using the same RT-PCR with slight
      modifications. The results of RT-PCR correlated well with the results of the
      immunofluorescent test for the same samples tested at the Purdue University
      Animal Disease Laboratory, West Lafayette, Indiana. The nucleotide sequence and
      projected amino acid sequence comparison of the P gene of different isolates of
      TCoV from 5 different states in the United States revealed a close association
      among the different isolates of TCoV.

PMID- 14667028
TI  - Seroprevalence of antibodies to Sarcocystis neurona in equids residing in
      Oklahoma.
AB  - A sampling of equids from the state of Oklahoma produced an estimate of
      seroprevalence of antibody to Sarcocystis neurona to be about 89.2%. This figure
      represents the highest currently reported regional seroprevalence of antibody to
      this organism. Regional differences in seroprevalence were found in the western
      quadrants of the state relative to the eastern quadrants of the state, with a
      significantly higher seroprevalence in the eastern regions. Thoroughbreds were
      found to exhibit a statistically significant lower seroprevalence as a breed
      group when compared with other breeds sampled.

PMID- 14667029
TI  - Haematological analyses in rainbow trout Oncorhynchus mykiss affected by viral
      haemorrhagic septicaemia (VHS).
AB  - Rainbow trout Oncorhynchus mykiss weighing 87 +/- 15 g (mean +/- SD) were
      infected with viral haemorrhagic septicaemia virus (VHSV) and the haematological
      and biochemical profiles of peripheral blood examined. Depending on the clinical
      signs and gross pathology, the fish were divided into 2 groups: Group A included
      fish in the acute stage, Group B comprised fish in the chronic stage. Red blood
      cells were subjected to 6 haematological tests and blood plasma to 14 biochemical
      tests, which provided findings on changed substrate concentrations and enzyme
      activities. Diseased fish, compared to healthy fish, had a significantly lower
      red blood cell count, and lower haematocrit and haemoglobin levels. As for the
      biochemical parameters, the fish had less total protein, creatinine, glucose,
      triacylglycerol, inorganic phosphate, total calcium and sodium, and more blood
      urea, nitrogen and potassium. Uric acid levels remained unchanged. Increases were
      recorded in the catalytic concentration of alanine aminotransferase, aspartate
      aminotransferase and lactate dehydrogenase. A decrease was recorded in the
      catalytic concentration of alkaline phosphatase. Fish with VHS in the chronic
      stage, compared with healthy fish, were in worse condition, with a significantly
      reduced Fulton coefficient and Clark coefficient, and a higher hepatosomatic
      index and visceral somatic index.

PMID- 14667030
TI  - Effect of intraperitoneally administered IL-1beta-derived peptides on resistance
      to viral haemorrhagic septicaemia in rainbow trout Oncorhynchus mykiss.
AB  - The present work provides the first information concerning the immunostimulatory
      activity of trout interleukin (IL)-1beta-derived peptides in vivo. Previous
      studies have demonstrated the ability of 2 such peptides, referred to as P1 and
      P3, to up-regulate a range of important immune parameters in vitro. P1
      corresponds to fragment 146-157 (YVTPVPIETEAR) of the trout sequence and is
      analogous to a biologically active mammalian IL-1beta-derived peptide, whilst P3
      was synthesised to complex with the IL-1 receptor and corresponds to fragment 197
      206 (YRRNTGVDIS) of the trout sequence. Optimal migration of peritoneal
      leucocytes, peptide induced phagocytosis and intracellular respiratory burst
      activity occurred following intraperitoneal injection of 3.0 micromol of P3.
      Furthermore, resistance to viral haemorrhagic septicaemia virus (VHSV) was soon
      augmented (2 d) post-injection of P3.

PMID- 14667031
TI  - Characterization of aquabirnaviruses from flounder Pseudopleuronectes americanus
      and mummichog Fundulus heteroclitus in the Chesapeake Bay, Virginia, USA.
AB  - Viruses were isolated in cell culture from tissue homogenates of flounder
      Pseudopleuronectes americanus and mummichog Fundulus heteroclitus in the
      Chesapeake Bay, Virginia, USA. Neutralization and immunofluorescence tests with
      aquabirnavirus (West Buxton strain)-specific polyclonal antisera indicated that
      both viruses were aquabirnaviruses belonging to Serogroup A, the most common
      aquabirnavirus serogroup in the United States. This was confirmed by RT-PCR, with
      primers targeting the VP3 and VP2 gene of aquabirnaviruses. The VP2-specific RT
      PCR cDNA amplification product was sequenced and deduced amino-acid sequences
      were compared with known sequences of the type strains of the 9 serotypes of
      aquabirnavirus Serogroup A. This demonstrated that the viruses from both flounder
      and mummichog belong to aquabirnavirus Genogroup 1. The flounder isolate
      exhibited deduced amino acid sequence similarities of 98.1% with the Jasper
      strain of serotype A9, and 97.7% with the West Buxton strain of serotype A1. The
      isolate from mummichog exhibited deduced amino acid sequence similarities of
      99.1% with the West Buxton strain of Serotype A1 and 94.8% with the Jasper
      isolate of Serotype A9. Similarities of deduced amino acid sequences ranged from
      79.9 to 86.9%, with representatives of the other 7 serotypes. This is the first
      report of an aquabirnavirus from mummichog F. heteroclitus and only the fifth
      report of an aquabirnavirus from a flounder species.

PMID- 14667032
TI  - Genotyping of Flavobacterium psychrophilum using PCR-RFLP analysis.
AB  - Genetic variability among 242 strains of Flavobacterium psychrophilum was
      characterized using polymerase chain reaction (PCR) followed by restriction
      fragment length polymorphism (RFLP) analysis. Universal Primers GYR-1 and GYR-1R,
      which were designed to amplify the gyrase subunit B gene (gyrB), yielded a 1178
      bp PCR product encoding gyrB and a 290 bp PCR product of anonymous DNA from all
      F. psychrophilum strains tested. In the RFLP analysis of the anonymous 290 bp DNA
      marker, the restriction enzyme HinfI generated 2 cleavage patterns (Genotypes A
      and B). Genotype A was found only in isolates from ayu (n = 109), while Genotype
      B was found in isolates from coho salmon (n = 11), ayu (n = 35), rainbow trout (n
      = 43) and other fishes (n = 44). In the second experiment, Primers PSY-G1F and
      PSY-G1R specific for F. psychrophilum, were used to amplify gyrB. The specific
      primer pair amplified the expected size (1017 bp) PCR product from all F.
      psychrophilum strains. In the RFLP analysis of the gyrB, the restriction enzyme
      RsaI produced 2 genotypes, R and S. Genotype R was found in isolates from coho
      salmon (n = 6), ayu (n = 27), rainbow trout (n = 39) and other fishes (n = 4).
      Genotype S was found in isolates from coho salmon (n = 5), ayu (n = 117), rainbow
      trout (n = 4) and other fishes (n = 40).

PMID- 14667033
TI  - Epizootiology and histopathology of Parvicapsula sp. in coho salmon Oncorhynchus
      kisutch.
AB  - The epizootiology and histopathology of the myxosporean Parvicapsula sp. was
      studied during monthly health surveys of 4 groups of coho salmon Oncorhynchus
      kisutch at a commercial farm in Puget Sound, Washington, USA, from 1984 to 1986.
      No Parvicapsula sp. was detected in histological samples taken from juvenile fish
      in fresh water, but the parasite was detected in fish from all groups 2 to 8 mo
      after transfer to seawater net pens. Groups placed in seawater net pens in
      November and December had a higher prevalence of infection, and a longer period
      of continuous detected infection, than those introduced into net pens in May. For
      the groups transferred to seawater in November and December, the highest
      infection prevalence (45 to 90%) was detected during the following March and
      April. Among 13 tissues examined histologically, only the pseudobranch and kidney
      were positive for Parvicapsula sp., with 26 (62%) of 42 positive fish showing
      infections only in the pseudobranch, 5 (12%) showing infections only in the
      kidney, and 11 (26%) showing infections in both organs. Both the pseudobranch and
      kidney were apparent primary infection sites, but pseudobranch infections
      appeared to persist longer in a population. Pseudobranch infections were
      frequently heavy and associated with extensive inflammation and necrosis of
      filament and lamellar tissues. The kidney had been the only infection site
      reported for Parvicapsula sp. in previous studies of coho salmon.

PMID- 14667034
TI  - Spatio-temporal dynamics of the parasitic nematode Anguillicola crassus in
      Flanders, Belgium.
AB  - Despite Egusa's earlier warning of the damage that the parasitic nematode
      Anguillicola crassus could inflict on the European eel Anguilla anguilla, its
      introduction in Europe was a fact in the early 1980s. Based on an elaborate
      dataset on Anguillicola crassus infection of 11 river catchments, this paper
      presents the results of a detailed study on the dispersal of the parasite in
      Flanders, Belgium, and the host-parasite relationship. In addition, data from
      1986 and 1997 are used for comparative purposes, providing a perspective on the
      temporal infection pattern over 15 yr. The presence of A. crassus in Flanders was
      first discovered in 1985; 2 yr later a survey revealed a prevalence of 34.1% and
      a mean infection intensity of 5.5, based on adult nematodes only, and 10 yr later
      the parasite was present at all 11 sites sampled. Prevalence had increased to
      62.5 % but the mean infection intensity had decreased to 3.9 adults per infected
      eel. Finally, in the year 2000, a third study revealed that A. crassus was
      present in 139 of 140 investigated sites; a further increase in prevalence to
      68.7% and a decrease in mean infection intensity to 3.4 adults per infected eel
      was observed. When all larval stages were taken into account, mean prevalence
      amounted to 88.1% and mean intensity to 5.5 adults. The high infection level in
      Flanders is thought to be the result of restocking with glass eel and yellow eel,
      both of which are susceptible to A. crassus. The general infection parameters
      were similar in all 11 river catchments. It is possible that in Flanders both
      prevalence and mean infection intensity are stabilizing due to density-dependent
      regulation of the parasite infrapopulation. Fibrotic swimbladder walls were
      observed, mainly in large eels, and 20% of the total number of nematodes
      consisted of encapsulated larvae in the surveys of 1997 and 2000; 8 cases of
      swimbladder regeneration were observed.

PMID- 14667035
TI  - Mucous cell responses in gill and skin of brown trout Salmo trutta fario in
      acidic, aluminium-containing stream water.
AB  - Morphometric examination was carried out on the gills and skin of wild and caged
      hatchery brown trout Salmo trutta fario in an acidic (pH 4.9 to 5.4; Al 203 to
      250 microg l(-1)) and in a non-acidic (pH 6.7 to 7.0; Al 27 to 67 microg l(-1))
      stream in the Vosges Mountains (NE France) to assess the sublethal effects of
      acidic water on the mucous cell response. The caged fish were randomly collected
      after 2, 4, 7 and 11 d and the wild fish were obtained by electrofishing. After 2
      d, a reduction of both mucous cell (MC) number and size was observed in the gills
      of fish held in the acidic stream, suggesting a massive mucus discharge.
      Hyperplasia and hypertrophy of cells immediately followed this mucus secretion.
      In the same fish population, skin examination showed a slight and delayed
      decrease of MC number but a significant increase of cell size. The number of
      mucous cells of gills and skin was similar in both wild trout populations,
      whereas a significant MC hypertrophy was observed in the wild fish of the acidic
      stream. The present field experiment indicates that caged fish could be useful as
      early indicators of acidification. In addition, the examination of wild
      populations suggested the occurrence of adaptive mechanisms, information that
      might be of importance in the context of river recovery programs.

PMID- 14667036
TI  - Cardiomyopathy syndrome in farmed Atlantic salmon Salmo salar: occurrence and
      direct financial losses for Norwegian aquaculture.
AB  - Cardiomyopathy syndrome (CMS) was first diagnosed in the mid-1980s in farmed
      Atlantic salmon in Norway, and later also in Scotland and the Faeroe Islands. In
      Norway the number of diagnosed cases increased from 25 to 103 in the period from
      1998 to 2001 according to the National Veterinary Institute (NVI) records. Very
      little is known about the causes of the disease and there is no documentation of
      its impact on the farmed salmon industry. This field survey was performed to
      collect information on occurrence, risk factors and the economic importance of
      CMS in sea farmed Atlantic salmon Salmo salar in Norway. Data were collected in
      January 2001 from a total of 174 groups of farmed salmon which had been
      previously transferred to sea during 1999 and 2000. Approximately 11.5% of all
      groups of salmon in our study experienced cases of CMS. Affected fish were
      presumably in generally good condition prior to time of death. In fish which had
      completed the seawater production cycle, CMS occurred more than 1 yr (median 395
      d, >2 kg body weight) after seawater transfer. In fish transferred into the sea
      during autumn 2000 which had not completed the seawater cycle during the study
      period, CMS was diagnosed at a weight as low as 700 g. Although sudden death is
      characteristic, CMS may be regarded as a chronic disease, with moderately
      elevated mortality rates at site level. Affected groups showed significantly
      increased mortality, causing a direct annual financial loss for the industry of
      Euros 4.5 to 8.8 million on fish farms. Preventive prescheduled slaughtering of
      salmon, which is performed on many affected farms, may be too costly when done
      too early.

PMID- 14667037
TI  - Salinity effects on immune parameters of Ruditapes philippinarum challenged with
      Vibrio tapetis.
AB  - The occurrence of brown ring disease (BRD) in farmed Manila clams Ruditapes
      philippinarum is seasonal. Development of the disease is believed to require the
      presence of the infective agent Vibrio tapetis and particular environmental
      conditions. This paper studies the effect of salinity (20 to 40 per thousand) on
      measurable immune parameters of Manila clams, and the progression of BRD in
      experimentally infected individuals. At 20 per thousand salinity, the total
      haemocyte count was reduced and disease prevalence was highest. At 40 per
      thousand salinity significantly fewer clams presented signs of BRD, and this was
      correlated with increases in the total haemocyte count, hyalinocyte count,
      phenoloxidase levels and phagocytic activity of haemocytes. Inoculation of clams
      with V. tapetis did not have a significant effect on the immune parameters
      measured. Thus, this laboratory-based study relates environmental stress to
      disease development.

PMID- 14667038
TI  - Prevalence and infection intensity of the ovarian parasite Marteilioides
      chungmuensis during an annual reproductive cycle of the oyster Crassostrea gigas.
AB  - The occurrence of Marteilioides chungmuensis, a protozoan paramyxean parasite in
      the reproductive system of the Pacific oyster Crassostrea gigas, was observed at
      Gosung Bay, Korea. Seasonal variation in gonad development was investigated in a
      suspended cultured oyster population. Gametogenesis began in February and first
      spawning was observed between mid and late June when surface water temperature
      reached 22 to 25 degrees C. Spawning activity extended from mid June to late
      September, with 2 marked spawning peaks in June and August. Histological
      examination indicated that gonad development paralleled seasonal fluctuations in
      water temperature. Spawning in late June was partly associated with a sudden drop
      in salinity due to large freshwater inputs to the Bay with the summer monsoon. M.
      chungmuensis occurred in developing and fully mature eggs of spawning oysters in
      late June to January, but were not observed from February to May. Monthly mean
      infection intensity was high in late June when most oysters had their first
      spawning period. The infection level was also relatively high in late August and
      November, when oysters were spawning or had completed spawning. Several oysters
      collected in November (11.4%) and December (16.3%) carried a large quantity of
      ripe but M. chungmuensis-infected eggs, suggesting that infection also causes
      spawning failure by delaying spawning and destroying ripe oocytes.

PMID- 14667039
TI  - Argyrophilic nucleolar organizer regions (AgNORs) in interphases and metaphases
      of normal and neoplastic gill cells of Macoma balthica (Bivalvia: Tellinidae)
      from the Gulf of Gdansk, Baltic Sea.
AB  - Chromosome analysis of gill cells of different populations of Macoma balthica
      (L.) from the Bay of Gdansk (Baltic Sea) revealed 2 clam categories, 1 with
      neoplastic features and 1 without. Silver-staining was performed on interphase
      and metaphase cells of both categories. The mean argyrophilic nucleolar organizer
      region (AgNOR) count per abnormal interphase cell was significantly higher than
      in normal interphase cells. Normal silver-stained metaphases had 3 nucleolar
      organizer region (NOR) chromosome phenotypes. The location of the NORs in the
      most frequent phenotype (55.6% in 54 metaphases scored) was interstitial on the
      largest metacentric chromosome pair, Pair No. 1. Abnormal silver-stained
      metaphases had a higher number of active NOR sites. Different phenotypes were
      observed (frequency greater than 10% for 67 metaphases scored); 2 were similar to
      those in normal metaphases and 5 were ectopic. The higher activity of AgNORs
      observed in abnormal cells confirmed the diagnosis of malignant neoplasia.

PMID- 14667040
TI  - Lactococcus garvieae in wild Red Sea wrasse Coris aygula (Labridae).
AB  - Lactococcus garvieae infection in wild wrasse Coris aygula is reported, and the
      serological and molecular characteristics of the isolate are described. This is
      the first evidence of the presence of this pathogen in the Red Sea, and it
      follows the recent diagnosis of Mycobacterium marinum and Streptococcus iniae in
      wild fish from the same region. Whether all 3 pathogens are strains endemic to
      the Red Sea, or recent introductions into the region, remains to be determined,
      but their appearance over a period of a few years in wild fish populations in the
      northern Red Sea is consistent with an emerging trend affecting marine organisms
      on a global level in areas subjected to intense anthropogenic impacts.

PMID- 14667041
TI  - Potential use of stem cells in neuroreplacement therapies for neurodegenerative
      diseases.
AB  - The use of stem cells for neuroreplacement therapy is no longer science fiction-
      it is science fact. We have succeeded in the development of neural and
      mesenchymal stem cell transplantation to produce neural cells in the brain. We
      have also seen improvement in cognitive function following stem cell
      transplantation in a memory-impaired aged animal model. These results promise a
      bright future for stem cell therapies in neurodegenerative diseases. Before we
      begin to think about clinical applications beyond the present preclinical
      studies, we have to consider the pathophysiological environment of individual
      diseases and weigh the factors that affect stem cell biology. Here, I not only
      review potential therapeutic applications of stem cell strategies in
      neurodegenerative diseases, but also discuss stem cell biology regarding factors
      that are altered under disease conditions.

PMID- 14667042
TI  - From genes to photosynthesis in Arabidopsis thaliana.
AB  - Although photosynthesis in higher plants is of cyanobacterial descent, it differs
      strikingly in organization and regulation from the prokaryotic process. Genomics,
      proteomics, and comparative genome analysis are now providing powerful new tools
      for the molecular dissection of photosynthesis in higher plants. Mutant screens
      and reverse genetics identify an increasing number of gene-function relationships
      that have a bearing on photosynthesis, revealing a marked interdependency between
      photosynthesis and other cellular processes. Photosynthesis-related functions are
      mostly located in the chloroplast, but can also be located in other compartments
      of the plant cell. The analysis by DNA-array hybridization of mRNA expression
      patterns both in the chloroplast and the nucleus, under various environmental
      conditions and/or in different genetic backgrounds that affect the function of
      the plastid, is rapidly improving our understanding of how photosynthesis is
      regulated, and it reveals that plastid-to-nucleus signaling plays a central role
      in its control.

PMID- 14667043
TI  - Homologous recombination and gene targeting in plant cells.
AB  - Gene targeting has become an indispensable tool for functional genomics in yeast
      and mouse; however, this tool is still missing in plants. This review discusses
      the gene targeting problem in plants in the context of general knowledge on
      recombination and gene targeting. An overview on the history of gene targeting is
      followed by a general introduction to genetic recombination of bacteria, yeast,
      and vertebrates. This abridged discussion serves as a guide to the following
      sections, which cover plant-specific aspects of recombination assay systems, the
      mechanism of recombination, plant recombination genes, the relationship of
      recombination to the environment, approaches to stimulate homologous
      recombination and gene targeting, and a description of two plant systems, the
      moss Physcomitrella patens and the chloroplast, that naturally have high
      efficiencies of gene targeting. The review concludes with a discussion of
      alternatives to gene targeting.

PMID- 14667044
TI  - Redox control, redox signaling, and redox homeostasis in plant cells.
AB  - Redox chemistry is a key feature of life. Oxidized substrates are reduced to
      synthesize functional molecules; reduced substrates are oxidized for energy
      supply. In addition, cells must fight against uncontrolled oxidation of essential
      constituents, a process that continuously occurs in an atmosphere of 21% O2. The
      redox situation is further complicated in plants with their highly reactive
      photosynthetic metabolism. To this end it is now well established that redox
      regulation is a central element in adjusting plant metabolism and development to
      the prevailing environmental conditions. This review introduces general redox
      chemistry and the main components of the cellular redox network, namely pyridine
      nucleotides, ascorbate, glutathione, lipoic acid, tocopherol, thioredoxins,
      glutaredoxins, peroxiredoxins, and other thiol proteins. Examples for redox
      sensing, transduction, redox-regulated enzymes and transcription, and the
      function of regulatory circuits are presented. Emphasis is placed on redox
      regulation of photosynthesis, which is the best understood metabolism governed by
      redox control on essentially all levels, ranging from gene transcription to
      translation, assembly and turnover, as well as short-term adaptation by state
      transition and enzyme activity. Increasing evidence shows the importance of redox
      regulation in the context of transport, plant development, and programmed cell
      death.

PMID- 14667045
TI  - The cellular and molecular bases of vertebrate lens regeneration.
AB  - Lens regeneration takes place in some vertebrates through processes of cellular
      dedifferentiation and transdifferentiation, processes by which certain
      differentiated cell types can give rise to others. This review describes the
      principal forms of lens regeneration that occur in vivo as well as related in
      vitro systems of transdifferentiation. Classic experimental studies are reviewed
      that define the tissue interactions that trigger these events in vivo. Recent
      molecular analyses have begun to identify the genes associated with these
      processes. These latter studies generally reveal tremendous similarities between
      embryonic lens development and lens regeneration. Different models are proposed
      to describe basic molecular pathways that define the processes of lens
      regeneration and transdifferentiation. Finally, studies are discussed suggesting
      that fibroblast growth factors play key roles in supporting the process of lens
      regeneration. Retinoids, such as retinoic acid, may also play important roles in
      this process.

PMID- 14667047
TI  - Enumeration and simulation of marriage node graphs on zero-loop pedigrees.
AB  - We present a method that for the marriage node graph of a zero-loop pedigree will
      enumerate all possible pedigrees that share the same underlying tree structure.
      The enumeration method leads naturally to a scheme for simulating from a uniform
      distribution on such pedigrees. This is extended to simulating pedigrees for
      which the underlying marriage node graph is a tree of any particular size.

PMID- 14667046
TI  - Modelling host tissue degradation by extracellular bacterial pathogens.
AB  - Extracellular bacterial pathogens such as Pseudomonas aeruginosa are able to
      penetrate into host tissues (given an initial breech in the outer barrier, e.g. a
      wound) through the action of exo-toxins and degradative exo-enzymes. A
      mathematical model of this process is presented which, in the absence of
      significant immune response, predicts the progression of the bacteria into the
      tissue as a travelling wave whose velocity can be determined explicitly in terms
      of the model parameters. Simple in vitro experiments in protein-based matrices
      are performed which yield results consistent with this behaviour. A complementary
      in vitro experimental system with distinct qualitative behaviour is also studied,
      giving further insight and confidence in the modelling approach.

PMID- 14667048
TI  - Mathematical modelling of comedo ductal carcinoma in situ of the breast.
AB  - The growth of a tumour in a cylindrical duct with compliant walls is examined in
      order to model the early stages of ductal carcinoma in situ (DCIS) of the breast,
      the earliest known stage of breast cancer. A nutrient-limited growth model is
      formulated, in which cell movement is described by a Stokes flow constitutive
      relation. The interactions between the expansive forces created by tumour cell
      proliferation and the stresses that develop in the compliant basement membrane
      are studied using asymptotic and numerical methods. In this way we show how the
      duct wall deforms as the tumour grows and also how the progression of the tumour
      along the duct depends upon the stiffness of the wall. By varying key parameters
      we determine how treatment, protease production and the inclusion of the
      surrounding stroma affect the growth. Finally, we discuss the biological
      relevance of our results and suggest possible directions for future work.

PMID- 14667049
TI  - Insecticidal activity of the enantiomers of fipronil.
AB  - The two enantiomers of the insecticide fipronil were made by preparative HPLC.
      The insecticidal activities of the racemic mixture and the two enantiomers
      against selected agricultural or household pests (cotton stainer, Dysdercus
      cingulatus F; grain weevil, Sitophilus granarius L and house fly, Musca domestica
      L) were determined. There was no significant difference in acute or residual
      activity between the racemic mixture and the enantiomers of fipronil, indicating
      that there is no preferred chiral form of the compound in these key species of
      important insects. This observation clearly suggests that there is no major scope
      for marketing the insecticide in a one-enantiomer form.

PMID- 14667050
TI  - Modelling approaches to compare sorption and degradation of metsulfuron-methyl in
      laboratory micro-lysimeter and batch experiments.
AB  - Results of laboratory batch studies often differ from those of outdoor lysimeter
      or field plot experiments--with respect to degradation as well as sorption.
      Laboratory micro-lysimeters are a useful device for closing the gap between
      laboratory and field by both including relevant transport processes in
      undisturbed soil columns and allowing controlled boundary conditions. In this
      study, sorption and degradation of the herbicide metsulfuron-methyl in a loamy
      silt soil were investigated by applying inverse modelling techniques to data sets
      from different experimental approaches under laboratory conditions at a
      temperature of 10 degrees C: first, batch-degradation studies and, second, column
      experiments with undisturbed soil cores (28 cm length x 21 cm diameter). The
      column experiments included leachate and soil profile analysis at two different
      run times. A sequential extraction method was applied in both study parts in
      order to determine different binding states of the test item within the soil.
      Data were modelled using ModelMaker and Hydrus-1D/2D. Metsulfuron-methyl half
      life in the batch-experiments (t1/2 = 66 days) was shown to be about four times
      higher than in the micro-lysimeter studies (t1/2 about 17 days). Kinetic sorption
      was found to be a significant process both in batch and column experiments.
      Applying the one-rate-two-site kinetic sorption model to the sequential
      extraction data, it was possible to associate the stronger bonded fraction of
      metsulfuron-methyl with its kinetically sorbed fraction in the model. Although
      the columns exhibited strong significance of multi-domain flow (soil
      heterogeneity), the comparison between bromide and metsulfuron-methyl leaching
      and profile data showed clear evidence for kinetic sorption effects. The use of
      soil profile data had significant impact on parameter estimates concerning
      sorption and degradation. The simulated leaching of metsulfuron-methyl as it
      resulted from parameter estimation was shown to decrease when soil profile data
      were considered in the parameter estimation procedure. Moreover, it was shown
      that the significance of kinetic sorption can only be demonstrated by the
      additional use of soil profile data in parameter estimation. Thus, the exclusive
      use of efflux data from leaching experiments at any scale can lead to fundamental
      misunderstandings of the underlying processes.

PMID- 14667051
TI  - The ability of indigenous micro-organisms to degrade isoproturon, atrazine and
      mecoprop within aerobic UK aquifer systems.
AB  - The potential for the herbicides isoproturon, atrazine and mecoprop to degrade in
      the major UK aquifers of chalk, sandstone and limestone was studied using
      laboratory microcosms spiked at 100 microg litre(-1). Significant mecoprop
      degradation was only observed in sandstone groundwater samples. Atrazine
      transformation, based on the formation of metabolites, did occur in most
      groundwater samples, but only at a rate of 1-3% per year. A potential to degrade
      isoproturon was observed in groundwater samples from each of the aquifer types,
      with the most rapid and consistent degradation occurring at the sandstone field
      site. Biodegradation was confirmed by the formation of monodesmethyl- and
      didesmethyl-isoproturon. Isoproturon degradation potential rates obtained from
      the groundwater microcosms could not be correlated with either dissolved organic
      carbon or numbers of bacteria in the groundwater. It was noted that the ability
      of the groundwater at a field site to degrade a pesticide was not related to
      performance of the soil above.

PMID- 14667052
TI  - Linking fluorescence induction curve and biomass in herbicide screening.
AB  - A suite of dose-response bioassays with white mustard (Sinapis alba L) and sugar
      beet (Beta vulgaris L) in the greenhouse and with three herbicides was used to
      analyse how the fluorescence induction curves (Kautsky curves) were affected by
      the herbicides. Bentazone, a photosystem II (PSII) inhibitor, completely blocked
      the normal fluorescence decay after the P-step. In contrast, fluorescence decay
      was still obvious for flurochloridone, a PDS inhibitor, and glyphosate, an EPSP
      inhibitor, which indicated that PSII inhibition was incomplete. From the numerous
      parameters that can be derived from OJIP-steps of the Kautsky curve the relative
      changes at the J-step [Fvj = (Fm - Fj)/Fm] was selected to be a common response
      parameter for the herbicides and yielded consistent dose-response relationships.
      Four hours after treatment, the response Fvj on the doses of bentazone and
      flurochloridone could be measured. For glyphosate, the changes of the Kautsky
      curve could similarly be detected 4 h after treatment in sugar beet, but only
      after 24 hs in S alba. The best prediction of biomass in relation to Fvj was
      found for bentazone. The experiments were conducted between May and August 2002
      and showed that the ambient temperature and solar radiation in the greenhouse
      could affect dose-response relationships. If the Kautsky curve parameters should
      be used to predict the outcome of herbicide screening experiments in the
      greenhouse, where ambient radiation and temperature can only partly be
      controlled, it is imperative that the chosen fluorescence parameters can be used
      to predict accurately the resulting biomass used in classical bioassays.

PMID- 14667053
TI  - Investigation of alternatives to methyl bromide for management of Meloidogyne
      javanica on greenhouse grown tomato.
AB  - The root galling index and the densities of eggs in roots and juveniles in soil
      of the root-knot nematode Meloidogyne javanica (Treub) Chitwood on tomato, and
      the effect of these on crop yield were assessed in greenhouse experiments
      applying various treatments at two different sites in Crete, Greece. Tomato crops
      were grown for four cycles by rotating nematode-resistant (first and third spring
      crops) with susceptible (second and fourth autumn crops) cultivars and receiving
      the following treatments: (a) untreated control; (b) methyl bromide application
      before the first and third crops; (c) application of the fungus Pochonia
      chlamydosporia (Goddard) Zare, Gams & Evans before planting the first, third and
      fourth crops with a supplementary application three weeks after the beginning of
      the fourth crop; (d) application of oxamyl in both sites and fenamiphos in site 1
      only at the second and fourth crops; (e) combination of treatments (c) and (d).
      The fungus density in soil was monitored three weeks after application and at the
      end of each crop, when roots were lifted. Pochonia chlamydosporia had a variable
      establishment and did not control the nematode. Its pathogenicity on eggs was not
      demonstrated, as in all cases galls were big, with all egg masses inside and
      protected from infection. The methyl bromide treatment significantly reduced root
      galling and egg production compared to other treatments in all crop cycles and
      the yield of the fourth crop was significantly greater. Nematicides reduced
      nematode densities compared with untreated controls and the fungus treatment, but
      they were less effective than methyl bromide and resulted in increased yield in
      one site only.

PMID- 14667054
TI  - An index for selective toxicity of miticides to phytophagous mites and their
      predators based on orchard trials.
AB  - Data from nine trials conducted from 1990 to 1998 in apple orchards in Nova
      Scotia and Quebec, Canada, were used to estimate the predator-prey selectivity of
      miticides and their potential compatibility with biological control of mites. The
      European red mite Panonychus ulmi (Koch) was the dominant and more harmful
      phytophagous species, followed by the apple rust mite, Aculus schlechtendali
      (Nalepa). Two predacious mites, the phytoseiid, Typhlodromus pyri Sheuten, and
      the stigmaeid, Zetzellia mali (Ewing), were often found in the orchards. We used
      one minus the ratio of mite-days in treated plots to those in the control plots
      as an index of population suppression and toxicity of the miticides. Miticides
      were then categorized into classes similar to those employed by the International
      Organization for Biological Control to rate pesticide toxicity to natural enemies
      of insect and mite pests. Selectivity of miticides was mostly based on toxicity
      to P ulmi, the major pest, versus toxicity to T pyri, the major predator, with
      some consideration of the two lesser species, A schlechtendali and Z mali. In
      most cases, our findings were in accord with other studies. Abamectin and
      clofentezine had favourable selectivity (more toxic to the two phytophagous mites
      than to T pyri). The higher recommended rate of pyridaben (450 g ha(-1)) and two
      rates of spirodiclofen (180 and 240 g ha(-1)) were neutral (equally toxic to
      pests and predators). The lower rate of pyridaben (216 g ha(-1)), dicofol,
      formetanate hydrochloride and propargite were unfavourably selective (more toxic
      to T pyri). A higher than recommended rate of pyridaben (2160 g ha(-1)) applied
      before bloom was disruptive--P ulmi-days after treatment were actually greater
      than with the untreated control. P ulmi resistance to dicofol and propargite were
      probable complicating factors in some of the orchard trials.

PMID- 14667055
TI  - Multiple mechanisms account for variation in base-line sensitivity to azole
      fungicides in field isolates of Mycosphaerella graminicola.
AB  - Molecular mechanisms that account for variation in base-line sensitivity to azole
      fungicides were examined in a collection of twenty field isolates, collected in
      France and Germany, of the wheat pathogen Mycosphaerella graminicola (Fuckel)
      Schroeter. The isolates tested represent the wide baseline sensitivity to the
      azole fungicide tebuconazole described previously. The isolates were cross
      sensitive to other azoles tested, such as cyproconazole and ketoconazole, but not
      to unrelated chemicals like cycloheximide, kresoxim-methyl or rhodamine 6G.
      Progenies from a genetic cross between an isolate with an intermediate and a high
      sensitivity to azoles displayed a continuous range of phenotypes with respect to
      cyproconazole sensitivity, indicating that variation in azole sensitivity in this
      haploid organism is polygenic. The basal level of expression of the ATP-binding
      cassette transporter genes MgAtr1-MgAtr5 from Mgraminicola significantly varied
      amongst the isolates tested, but no clear increase in the transcript level of a
      particular MgAtr gene was found in the less sensitive isolates. Cyproconazole
      strongly induced expression of MgAtr4, but no correlation between expression
      levels of this gene and azole sensitivity was observed. One isolate with
      intermediate sensitivity to azoles over-expressed CYP51, encoding cytochrome P450
      sterol 14alpha-demethylase from M graminicola. Isolates with a low or high
      sensitivity to azoles were tested for accumulation of cyproconazole, but no clear
      correlation between reduced accumulation of the fungicide in mycelium and
      sensitivity to azoles was observed. Therefore, differences in accumulation cannot
      account exclusively for the variation in base-line sensitivity of the isolates to
      azoles. The results indicate that multiple mechanisms account for differences in
      base-line sensitivity to azoles in field isolates of M graminicola.

PMID- 14667056
TI  - Development of a new application apparatus for entomopathogenic nematodes.
AB  - This paper describes the assessment of nematode spray application methods and
      details the redesign of a spinning disc applicator for the improved application
      of the infective juveniles of entomopathogenic nematodes to foliage. The
      assessment highlighted fundamental design features that prevent efficient and
      accurate nematode application and these are dealt with in turn specifically to
      enable improved nematode application. The redesigned or prototype spinning disc
      was shown to improve nematode carriage in droplets, leading to greater deposition
      of nematodes per unit area. There is a trade-off between spray droplet coverage
      of the target surface and the production of a suitable droplet spectrum for
      nematode carriage.

PMID- 14667057
TI  - Partial characterization and insecticidal properties of Ricinus communis L
      foliage flavonoids.
AB  - Aqueous leaf extract of Ricinus communis L (Euphorbiaceae), a cultivated plant in
      tropical countries, showed excellent insecticidal activity against Callosobruchus
      chinensis L (Coleoptera: Bruchidae). We have isolated and tested flavonoids as
      insecticidal and antimicrobial agents. The isolated flavonoids showed potential
      insecticidal, ovicidal and oviposition deterrent activities against C chinensis
      L. However, antimicrobial activity against the common microbial infestants of
      stored pulses, of which C chinensis is a major pest, was found to be
      insignificant. Two bands having Rf 0.63 and 0.69 were seen on HPTLC plates using
      mobile phase benzene + ethyl acetate + methanol + formic acid (12 + 4.5 + 2 + 1.5
      by volume) as eluant. The Rf values and scanning of the spectrum in the
      ultraviolet region, showed identity with the flavonoids quercetin and kaempferol.
      This was further confirmed using HPLC and IR and UV spectrometry. HPLC and HPTLC
      chromatograms also suggested quercetin to be the major flavonoid present in the
      hydrolyzed aqueous leaf extract of R communis.

PMID- 14667058
TI  - Selection for imidacloprid resistance in Nilaparvata lugens: cross-resistance
      patterns and possible mechanisms.
AB  - A field population of brown planthoppers (Nilaparvata lugens Stal) was collected
      and selected for imidacloprid resistance in the laboratory. The resistance
      increased by 11.35 times in 25 generations and the resistance ratio reached 72.83
      compared with a laboratory susceptible strain. The selected resistant strain
      showed obvious cross-resistance to all the acetylcholine receptor targeting
      insecticides tested (monosultap 1.44-fold, acetamiprid 1.61-fold, imidacloprid
      homologues JS599 2.46-fold and JS598 3.17-fold), but not to others. Further study
      demonstrated that TPP and DEM had no synergism on imidacloprid. However, PBO
      displayed significant synergism in some different strains, and the synergism
      increased with resistance (S strain 1.20, field population 1.43 and R strain
      2.93). PBO synergism to cross-resistant insecticides was also found in the
      resistant strain (monosultap 1.25, acetamiprid 1.39, JS598 1.94 and JS599 2.02).
      We concluded that esterase and glutathione S-transferase play little role in
      imidacloprid detoxification. The increase of the P450-monooxygenases
      detoxification is an important mechanism for imidacloprid resistance and target
      resistance may also exist in this species.

PMID- 14667059
TI  - Characterisation of castor oil by on-line and off-line non-aqueous reverse-phase
      high-performance liquid chromatography-mass spectrometry (APCI and UV/MALDI).
AB  - A non-aqueous reverse-phase HPLC method, based on two columns in series, has been
      used to separate the major triacylglycerols (TAGs) from commercial castor oil and
      to perform either on-line negative ion atmospheric pressure chemical ionisation
      (APCI), or off-line positive ion matrix-assisted laser desorption ionisation
      (MALDI)/MS. The resulting Mass Spectra showed chloride-attached TAG molecules [M
      + CI]- in the case of negative-ion APCI, and sodium-attached TAG molecules [M +
      Na]+ in the case of positive-ion MALDI. For MALDI time-of-flight (TOF)/MS, a
      liquid binary matrix system consisting of sodium ferrocyanide and glycerol was
      applied, resulting in excellent TAG sensitivity, which was necessary for the
      determination of trace amounts of TAGs in castor oil. Both techniques allowed
      unambiguous molecular mass determination of the intact TAG molecules with no
      thermal degradation. Furthermore, seamless post source decay (PSD) fragment ion
      analysis by means of a curved field reflector TOF mass spectrometer allowed the
      determination of the fatty acid composition of each individual TAG. Castor oil
      contained eight different TAGs which were successfully determined by both APCI
      and MALDI techniques. In each TAG, at least two units of 12-hydroxy-9
      octadecenoic acid (ricinoleic acid) were present. The following fatty acids were
      determined by seamless PSD fragment ion analysis and APCI/MALDI molecular mass
      determination as TAG substructures: ricinoleic acid, palmitic acid, stearic acid,
      oleic acid, linoleic acid, linolenic acid, dihydroxy stearic acid and eicosenoic
      acid. Triricinolein was the dominating TAG.

PMID- 14667060
TI  - The simultaneous determination of 1-aminocyclopropane-1-carboxylic acid and
      cyclopropane-1,1-dicarboxylic acid in Lycopersicum esculentum by high-performance
      liquid chromatography--electrospray tandem mass spectrometry.
AB  - Varying concentrations of cyclopropane-1,1-dicarboxylic acid (CDA), an inhibitor
      of 1-aminocyclopropane-1-carboxylic acid oxidase, added to the solid culture
      medium of tomato nodal shoot segments resulted in a reduction in the level of
      endogenous ethylene according to the concentration of inhibitor applied.
      Following treatment with inhibitor, plants were homogenised and the
      concentrations of CDA and of 1-aminocyclopropane-1-carboxylic acid (ACC) were
      measured simultaneously in the resulting juice using an HPLC-ESI/MS-MS method.
      The levels of CDA and ACC measured in the plant tissues were associated with the
      concentration of inhibitor added to the solid medium. The HPLC-ESI/MS-MS method
      described produced limits of detection of 0.8 pmol for ACC and of 4 pmol for CDA.

PMID- 14667061
TI  - Approach to the study of C-glycosyl flavones by ion trap HPLC-PAD-ESI/MS/MS:
      application to seeds of quince (Cydonia oblonga).
AB  - Ion trap HPLC-PAD-ESI/MS/MS has been used to study C-glycosyl flavones in quince
      seeds. Comparative analysis of the ions [(M-H)-60]-, [(M-H)-90]- and [(M-H)-120]-
      from 6-C- and 8-C-glycosyl flavone isomers, together with their respective
      retention times, allowed deductions to be made about the nature of the sugar
      units and the positions of C-glycosylation. Vicenin-2 (6,8-di-C-glucosyl
      apigenin), lucenin-2 (6,8-di-C-glucosyl luteolin), stellarin-2 (6,8-di-C-glucosyl
      chrysoeriol), isoschaftoside (6-C-arabinosyl-8-C-glucosyl apigenin), schaftoside
      (6-C-glucosyl-8-C-arabinosyl apigenin), 6-C-pentosyl-8-C-glucosyl chrysoeriol and
      6-C-glucosyl-8-C-pentosyl chrysoeriol were identified in quince seed.

PMID- 14667062
TI  - Quantification of sideroxylonals in Eucalyptus foliage by high-performance liquid
      chromatography.
AB  - This paper describes the extraction and quantification of sideroxylonals, a group
      of formylated phloroglucinol compounds found in the foliage of some eucalypt
      species. Samples of dry, ground foliage were Soxhlet-extracted with light
      petroleum spirit:acetone (4:1) and the resultant extract analysed (in the
      presence of internal standard) by reversed-phase HPLC without further
      purification. The yield of sideroxylonals was exponential with time and showed an
      inflection at ca. 4 h of extraction. It is recommended that samples be extracted
      for 6 h, giving a 92% recovery of the sideroxylonals. The title compounds
      deteriorate under various conditions, e.g. 10% are lost when foliage is oven
      dried at 40 degrees C compared to freeze-drying. Storing samples in mobile phase
      led to a slow deterioration of sideroxylonals with a 7% loss after 4 days, while
      22% of these compounds were lost from dry, ground eucalypt leaf stored at room
      temperature for 20 months.

PMID- 14667063
TI  - Determination of the lipid classes and fatty acid profile of Niger (Guizotia
      abyssinica Cass.) seed oil.
AB  - Niger seeds (Guizotia abyssinica Cass.), which are of interest as a new source of
      vegetable oils, were subjected to Soxhlet-extraction with n-hexane and the
      extract analysed using a combination of CC, GC, TLC and normal-phase HPLC. The
      total lipid content was ca. 300 mg/g seed material, and the fatty acid profile
      showed a high content of linoleic acid (up to 63%) together with palmitic acid
      (17%), oleic acid (ca. 11%), and stearic acid (ca. 7%). CC separation over silica
      gel eluted with solvents of increasing polarity yielded 291 mg/g of neutral
      lipids, 5.76 mg/g of glycolipids, and 0.84 mg/g of phospholipids. GC analysis
      showed that the major fatty acid present in all lipid classes was linoleic acid
      together with minor amounts of palmitic, oleic and stearic acids. Polar lipid
      fractions, however, were characterised by higher levels of palmitic acid and a
      lower content of linoleic acid. Phospholipid classes separated by normal-phase
      HPLC consisted of phosphatidylcholine (ca. 49%), phosphatidylethanolamine (22%),
      phosphatidylinositol (14%), phosphatidylserine (ca. 8%), and minor amounts (2-3%)
      of phosphatidylglycerol and lysophosphatidylcholine.

PMID- 14667064
TI  - Variation in the composition of the heartwood flavonoids of Prunus avium by on
      column capillary gas chromatography.
AB  - A fast and simple extraction procedure, coupled with on-column gas
      chromatography, has been developed in order to investigate the relative amounts
      of flavonoids in individual trees within several homogeneous populations of
      Prunus avium. Eight known flavonoid aglycones were isolated from the heartwood of
      P. avium and multivariate analysis was employed in order to characterise
      population groups.

PMID- 14667065
TI  - Quantification of tagitinin C in Tithonia diversifolia by reversed-phase high
      performance liquid chromatography.
AB  - A simple, rapid and reliable reversed-phase high-performance liquid
      chromatographic method for the determination of tagitinin C, an anti-plasmodial
      sesquiterpene lactone isolated from the aerial parts of Tithonia diversifolia,
      has been developed. The assay has been used to quantify tagitinin C in various
      extracts of the aerial parts of T. diversifolia.

PMID- 14667066
TI  - A bioassay for insect deterrent compounds found in plant and animal tissues.
AB  - A general field bioassay for detecting biologically active compounds in plants
      and insects has been developed and tested for efficacy and sensitivity.
      Methanolic extracts, in sucrose solution, of 20 plant and six caterpillar species
      were offered to the ponerine ant Paraponera clavata and the feeding preferences
      observed. The bioassay resulted in the detection of nine plant and three
      caterpillar species with ant-deterrent extracts, and 11 plant and three
      caterpillar species with neutral or attractant extracts. All of the plants
      showing ant-deterrent characteristics which had been chemically investigated in
      our laboratory, or for which chemical literature was available, contained
      secondary metabolites of known deterrence. Both naturally occurring and
      artificial differences in chemical concentrations could be detected using the
      bioassay. The method provides a means of screening plants and insects for
      compounds that are insect anti-feedants or that can modify insect behaviour.

PMID- 14667067
TI  - Current awareness in phytochemical analysis.

PMID- 14667068
TI  - Developing Mac Keith 'college'.

PMID- 14667069
TI  - Evolution in a journal.

PMID- 14667070
TI  - Factors associated with microcephaly at school age in a very-low-birthweight
      population.
AB  - The neonatal predictors of microcephaly, defined as a head circumference <5th
      centile in children born preterm, has not been systematically assessed. Children
      were drawn from the Developmental Epidemiology Network (DEN) cohort of very low
      birthweight children (VLBW: 500-1500g) born from 1991 to 1993 at three sites in
      the USA. Neurological assessments were carried out among 198 singleton children
      (mean age 6 years 8 months, SD 0.5 years). Ninety-six children (48.5%) were male.
      Microcephaly was observed in 30 children (15%) and, using multivariate analysis,
      it was found to be associated with gestational age <26 weeks and bronchopulmonary
      dysplasia (BPD). Sonography-defined white-matter damage (WMD, i.e. echolucency or
      echodensities) was not associated with increased odds of microcephaly, while
      occurrence of intraventricular hemorrhage (IVH) was in univariate but not
      multivariate analysis. In analyses that excluded children with IVH/WMD, odds of
      microcephaly increased in dose-related fashion according to number of days on
      ventilator: >5 days, OR=4.5; 95%CI=1.4 to 15; >10 days, OR=5.7; 95%CI=1.7 to 19;
      >15 days OR=8.3; 95% CI=2.3 to 29.2. Among children without BPD, microcephaly was
      not associated with differences in IQ, while IQ scores among children with BPD or
      any ventilation were disproportionately lower among those with microcephaly. In
      multivariate analyses predicting IQ at age 7 years, microcephaly was found to
      modify the association between neonatal lung disease and IQ.

PMID- 14667071
TI  - Stressful life events in pregnancy and head circumference at birth.
AB  - A strong association between stress in pregnancy and small head circumference in
      infants at birth was reported in 1994. This important finding has never been
      replicated. In a follow-up study of 4211 participants with singleton pregnancies,
      information on life events was collected twice during pregnancy and head
      circumference measured shortly after birth following standard procedures. No
      association was found between experienced or perceived stress as a result of life
      events during pregnancy and head circumference in the infants. In conclusion,
      stress in pregnancy may influence foetal brain development in many ways, but we
      found no support for an effect on the size of the brain as measured by head
      circumference at birth.

PMID- 14667072
TI  - Acquired epileptic dysgraphia: a longitudinal study.
AB  - A male presenting with benign partial epilepsy with rolandic spikes from the age
      of 7 years was evaluated at age 11 years for worsening of his epilepsy associated
      with a specific regression of graphomotor skills. A longitudinal study over
      nearly 2 years showed an improvement in handwriting to an almost normal level
      under modified antiepileptic therapy. A detailed analysis with a computer
      monitored graphics table showed at first a rapid improvement of skills followed
      by protracted slower progress. We argue that the initial rapid recovery of skills
      was directly linked to the improvement of his epilepsy. The slower late
      acquisition of motor programmes that had never been fully established was due to
      long-standing interference by his epilepsy. The specificity of the deficit within
      the graphomotor system and its possible neurobiological basis are also discussed.
      The analytical method and approach used in a single patient might provide an
      example for other patients in whom epilepsy can interfere in the acquisition,
      progress, and maintenance of new skills and can be responsible for selective
      deficits.

PMID- 14667073
TI  - Cognitive status of young adults with spina bifida.
AB  - The cognitive status of 168 Dutch young adults (103 females, 65 males; mean age
      20 years 9 months, age range 16 to 25 years) with spina bifida (SB) was examined.
      The main purpose was to establish the effect of the type of SB (occulta or
      aperta) and the effect of hydrocephalus (HC) within the group with SB aperta
      (AHC+). Results indicated, on average, a lower cognitive status of persons with
      AHC+ (n=111) than of persons with SB occulta (n=37) and of persons with SB aperta
      without HC (AHC-; n=20). Almost half the young adults with AHC+ had cognitive
      impairments of some sort. These included more domain specific impairments (70%)
      as well as a more general cognitive deficit (30%). Cognitive status of persons
      with SB occulta and of those with AHC- was similar to that in the healthy
      population. The presence of associated pathology, rather than SB per se, has a
      negative effect on cognitive status.

PMID- 14667074
TI  - Sensorimotor recovery in children after traumatic brain injury: analyses of gait,
      gross motor, and fine motor skills.
AB  - The recovery of gait, gross motor proficiency, and hand function was examined in
      23 children (13 males, 10 females; age 4 years 7 months to 15 years 10 months)
      with traumatic brain injury (TBI) over five months of in patient rehabilitation.
      We used gait analysis, the Gross Motor Function Measure, the Developmental Hand
      Function Test, and the Purdue Pegboard test. Brain injury had been severe
      (initial Glasgow Coma Scale GCS <8) in 17 children and moderate (GCS 8-10) in six
      children. Compared with healthy control children of the same age and sex,
      repeated gait analyses in ambulatory children with brain injury showed
      significant reductions of velocity, stride length and cadence, and impaired
      balance. Spatiotemporal gait variables were correlated with Gross Motor Function
      Measure scores. Hand function tests revealed deficits in fine motor skills,
      speed, and coordination. Degree of impairment increased with trauma severity.
      Despite significant improvements, differences in gait velocity, stride length,
      and hand function of children with brain injuries and controls were still present
      about 8 months after TBI. Hand motor skills improved less than gait. Young age at
      injury was not associated with better recovery.

PMID- 14667075
TI  - Ultrasound-guided botulinum toxin injection technique for the iliopsoas muscle.
AB  - Intramuscular botulinum toxin A injections are beneficial for the treatment of
      functional shortening of the iliopsoas muscle, but it is difficult to achieve
      precise needle positioning and injection. As a solution to this we present an
      ultrasound-guided injection technique for the iliopsoas muscle using an anterior
      approach from the groin. The procedure was performed 26 times in 13 patients
      (seven males, six females; mean age 11 years, SD 9 years 8 months; age range 4 to
      31 years), 10 times bilaterally. Indications were functional iliopsoas shortening
      due to cerebral palsy (17 hips), hereditary spastic paraplegia (four hips), and
      Perthes disease (five hips). In all cases the iliopsoas muscle was identified
      easily by ultrasound; the placement of the injection needle and injection into
      the site of interest were observed during real time. No complications were
      encountered. Botulinum toxin A (BTX-A) injections have become established as a
      standard procedure for the treatment of functional shortening of different
      muscles in persons with spasticity or dystonia (Kessler et al. 1999, Bakheit et
      al. 2001, Kirschner et al. 2001). Optimal needle placement is essential to avoid
      severe side effects and to assess lack of response to the drug or incorrect
      region of injection. While injection into superficial, very palpable muscles is
      quite easy, the approach to other muscles such as the iliopsoas muscle may be
      more difficult and the placement of the needle for an optimal injection site is
      harder to control. As a solution to this, we present an ultrasound-guided
      injection technique. The main indications for BTX-A injections in the iliopsoas
      muscle are dynamic hip flexion deformities mostly due to spastic conditions which
      may compromise walking (increased anterior pelvic tilt during the whole gait
      cycle, decreased hip extension at terminal stance, increased peak hip flexion
      during swing; Molenaers et al. 1999. Another indication might be decentration of
      the femoral head (as part of an injection programme which also includes other
      muscles like the adductors and the medial hamstrings) for pain relief, reducing
      care difficulties and, possibly, prevention of further decentration (Porta 2000,
      Foster et al. 2001, Deleplanque et al. 2002, Lubik et al. 2002). In Perthes
      disease, BTX-A injections in the iliopsoas muscle and the adductors may prevent a
      fixed deformity, which is a negative prognostic factor.

PMID- 14667076
TI  - Alternating hemiplegia of childhood: a syndrome inherited with an autosomal
      dominant trait.
AB  - Alternating hemiplegia of childhood is a rare disorder characterized by recurrent
      attacks of hemiplegia affecting either side of the body, oculomotor and autonomic
      disturbances, movement disorders, and progressive cognitive impairment. We report
      on one family with autosomal dominant alternating hemiplegia. The disorder was
      first recognized in a 9-year-old child, the third son of the family, who
      presented with learning disability, tonic-clonic seizures, dystonic attacks, and
      episodes of alternating hemiplegia starting at the age of 2 1/2 years. His mother
      and three brothers had similar symptoms. The maternal uncle, who has learning
      disability, had experienced multiple dystonic attacks. Tests performed on the
      family, including computerized tomography, magnetic resonance imaging, and
      magnetic resonance angiography of the brain as well as metabolic evaluation, were
      normal. Cytogenetic analysis was normal and mitochondrial DNA analysis revealed
      no deletions or mutations in the four affected family members and the
      grandmother. An autosomal dominant mode of inheritance is suggested by the fact
      that both sexes are affected in two generations.

PMID- 14667077
TI  - Intracerebral varicella-zoster virus reactivation in congenital varicella
      syndrome.
AB  - Patients with congenital varicella syndrome (CVS) typically present with clinical
      symptoms consisting of skin lesions, neurological defects, eye diseases, and/or
      limb hypoplasia. In rare cases, isolated manifestations in the brain or eye have
      been reported. The varicella-zoster virus (VZV), as the causative agent of CVS,
      could only be detected in a few infants with CVS. In addition, there is little in
      the literature on antiviral treatment of infants born with signs of CVS. We
      report a case of CVS in a male infant who presented with generalized clonic
      cerebral seizures at age 4 months. An endogenous intracerebral viral reactivation
      following intrauterine VZV infection was assumed. After the diagnosis was
      confirmed virologically, acyclovir was administered intravenously for 10 days and
      afterwards orally for 3 weeks. This antiviral treatment was aimed at preventing
      progression of the disease. We concluded from this case that infants with
      intrauterine VZV infection can suffer intracerebral VZV reactivations that
      require antiviral treatment.

PMID- 14667078
TI  - Epilepsy and perisylvian polymicrogyria in a patient with Kabuki syndrome.
AB  - Kabuki syndrome is a dysmorphogenic syndrome which has been reported in over 300
      patients since it was first described in Japan in 1981. In addition to its
      cardinal features (typical facies, mild-to-moderate learning disability, short
      stature, skeletal anomalies, and dermatoglyphic abnormalities with persistent
      foetal fingerpads), neurological anomalies are frequently reported, including
      epilepsy in 8% of those with the syndrome. We present here a 22-year-old white
      female patient with refractory partial epilepsy, Kabuki syndrome, and bilateral
      perisylvian polymicrogyria on MRI: the first reported case of this association.
      The aetiology of the syndrome, including the diverse genetic changes recognized,
      is then discussed.

PMID- 14667079
TI  - Early and self-injurious behavior in young children born at-risk: a preliminary
      analysis.

PMID- 14667080
TI  - Management of drooling: 10 years after the Consortium on Drooling 1990.

PMID- 14667081
TI  - Audit Office reviews progress on animal identification and tracking.

PMID- 14667082
TI  - Vet to be struck off for dishonesty.

PMID- 14667083
TI  - Progress in understanding brucellosis.

PMID- 14667084
TI  - Incidence of quinolone resistance in strains of Salmonella isolated from poultry,
      cattle and pigs in Germany between 1998 and 2001.
AB  - This paper reports the susceptibility to the quinolone nalidixic acid and the
      fluoroquinolone ciprofloxacin of 14,514 strains of Salmonella isolated in Germany
      from poultry, cattle and pigs between 1998 and 2001. Quinolone-resistant
      salmonellae were most frequently isolated from poultry, with a prevalence of 10.2
      to 16.8 per cent. Poultry-associated serotypes, such as Salmonella Paratyphi B (d
      tartrate positive), Salmonella Hadar and Salmonella Virchow, had the highest
      prevalence of quinolone resistance, ranging between 35 and 74 per cent. All the
      nalidixic acid-resistant strains also had a reduced susceptibility to
      ciprofloxacin, with minimum inhibitory concentrations (MICS) of 0.125 to 2
      microg/ml. A comparison of the MICS for ciprofloxacin of the strains of these
      poultry-associated serotypes and Salmonella Enteritidis phage type 4 isolated in
      1998/99 and 2000/01 indicated that there had been a shift towards higher MIC
      values of up to 2 microg/ml. The quinolone resistance-determining region (QRDR)
      of the gyrA gene and the homologue region of the parC gene of 31 selected strains
      were sequenced. Several different amino acid changes were observed in gyrA of the
      quinolone-resistant isolates at positions 83 and 87, but no substitutions were
      observed in parC.

PMID- 14667085
TI  - Clinical and radiographic study of bone and joint lesions in 26 dogs with
      leishmaniasis.
AB  - Twenty-six dogs with parasitologically confirmed leishmaniasis and abnormalities
      of gait were studied to determine the most common radiological patterns of bone
      and joint lesions. The clinical findings included either lameness, joint pain and
      crepitation, soft tissue swelling and/or muscle atrophy. Bone lesions were
      observed radiographically in 12 of the 26 dogs; the radius and ulna were affected
      in seven, the tibia in six and the femur in six. Joint lesions were observed
      radiographically in 15 of the 26 dogs; the carpus and stifle were affected in all
      15, and the tarsus in nine. There was a tendency for the bones and joints to be
      affected bilaterally. The radiographic patterns observed were different in the
      long bones and the joints. In the long bones, the most common pattern was
      periosteal and intramedullary proliferation, involving the diaphyses and related
      to the nutrient foramen; in the joints, two patterns, either non-erosive or
      erosive polyarthritis with soft-tissue swelling, were observed. The changes
      observed in the synovial fluid were associated in most cases with osteolytic
      lesions. However, Leishmania organisms were identified in the synovial fluid from
      joints without bony radiographic changes.

PMID- 14667086
TI  - Idiopathic granulomatous pneumonia in seven horses.
AB  - The history, clinical signs and pathological findings in seven adult horses with
      histologically confirmed idiopathic granulomatous disease, primarily of the
      lungs, are reviewed. They ranged in age from eight to 21 years, five were
      geldings and two were females, they belonged to five breeds and there were no
      seasonal or geographical associations. The primary clinical signs were chronic
      weight loss, exercise intolerance and respiratory distress which did not respond
      to conventional treatment. The most consistent physical findings were depression,
      anorexia, tachycardia, tachypnoea and adventitious lung sounds. Thoracic
      radiographs revealed a diffuse, structured, nodular, interstitial pulmonary
      pattern in each horse. Haematological measurements suggested a chronic
      inflammatory process and the cytology of transtracheal washes was consistent with
      a mild suppurative inflammation. Idiopathic granulomatous pneumonia was confirmed
      histologically in each of the horses, either postmortem or by a lung biopsy. The
      horses responded poorly to medical treatment and only one of three treated horses
      is still alive.

PMID- 14667087
TI  - Recovery of pathogenic Staphylococcus aureus from broiler hatchery air samples.

PMID- 14667088
TI  - Infestation of Dermestes carnivorus in a saker falcon (Falco cherrug).

PMID- 14667090
TI  - SPVS seminar for final-year students.

PMID- 14667089
TI  - BSE surveillance and emergency slaughter of cattle for human consumption.

PMID- 14667091
TI  - Electric shock collars and tail docking.

PMID- 14667092
TI  - Changing behaviour in the common horse tapeworm.

PMID- 14667093
TI  - Increased mortality on a free-range layer site.

PMID- 14667094
TI  - Renal artery stenosis: a new facet of the antiphospholipid (Hughes) syndrome.

PMID- 14667095
TI  - Left-sided heart valve abnormalities and risk of ischemic cerebrovascular
      accidents in patients with systemic lupus erythematosus.
AB  - The aim of the study was to assess the relationship between ischemic
      cerebrovascular accidents (ICVAs), that is, transient ischemic attack (TIA) or
      stroke, and left-sided heart valve abnormalities (LHVAs) in patients with
      systemic lupus erythematosus (SLE). In total, 71 consecutive SLE patients were
      studied. At baseline, history, clinical and laboratory evaluations, as well as
      trans-thoracic echocardiography (TTE) were performed. From the original
      population, so patients were followed up for a mean time of 5.80 +/- 1.53 years.
      After a mean period of 5.39 +/- 1.42 years; 40 patients underwent a repeat TTE.
      Previous ICVA history was present at baseline in 16 patients (22.5%). Of these,
      13 (81.2%) had evidence of LHVAs on TTE. Previous ICVAs were significantly
      associated to diagnosis of secondary anti-phospholipid syndrome (SAPS),
      positivity for anti-cardiolipin antibodies (aCl), and LHVAs. Multivariate
      analysis confirmed the correlation between previous ICVAs and LHVAs. LHVAs were
      not more commonly observed in patients with SAPS compared to patients without
      SAPS. At the end of follow-up, irrespective of any differences in antithrombotic
      treatment, ICVAs had occurred in 13 patients. During follow-up, ICVAs had
      recurred in seven patients, while a first event TIA occurred in one patient.
      Multivariate analysis confirmed the relationship between ICVAs and LHVAs, and a
      trend towards a positive correlation of the former with SAPS. This study
      demonstrates that LHVAs represent a compelling risk factor for the development of
      ICVAs in SLE patients. Conversely, SAPS and aCl positivity, although associated
      with ICVAs, did not clearly correlate with LHVAs in our study. These results
      provide insight on the pathogenesis of ICVAs and may give clues on the potential
      efficacy of preventive/therapeutic strategies in different SLE subpopulations.

PMID- 14667096
TI  - Cerebral hypoperfusion detected by SPECT in patients with systemic lupus
      erythematosus is related to clinical activity and cumulative tissue damage.
AB  - Cerebral single-photon emission computed tomography (SPECT) is a sensitive
      technique for the detection of central nervous system (CNS) involvement in
      systemic lupus erythematosus (SLE). The objective was to determine whether a
      relationship exists between cerebral hypoperfusion as detected by cerebral SPECT,
      cumulative tissue damage and the clinical activity of SLE. Cerebral technetium
      99m-L,L-ethyl cysteinate dimer (99mTc-ECD) SPECT was performed in two groups of
      patients: 10 women with SLE (Group A) who had no previous history of major
      neuropsychiatric (NPS) manifestations and no minor NPS symptoms in the last six
      months, and 57 unselected women with SLE (Group B). In the same week that SPECT
      was performed, the SLE disease activity index (SLEDAI), SLICC/ACR damage index,
      native anti-DNA antibodies (ELISA) and erythrocyte sedimentation rate (ESR) were
      determined. In Group A, cerebral SPECT showed moderate or severe hypoperfusion
      (abnormal SPECT) in five patients without NPS symptoms, unrelated to age (mean
      24.8 versus 27.8 years) or disease duration (mean 6.8 versus 9 years). Patients
      with significant cerebral hypoperfusion had greater clinical disease activity
      (mean SLEDAI 13.6 versus 7.6) (SLEDAI > 7 in 5/5 versus 1/5; Fisher: 0.023; OR:
      33; 95% CI: 2.3-469.8) and ESR (mean 43.6 versus 9.8; P < 0.05). In Group B, the
      mean age of the 57 unselected women with SLE was 37 years (SD 6.3) and the mean
      duration of the disease was 9.7 years (SD 6.3). Cerebral SPECT revealed normal
      perfusion or mild hypoperfusion (normal SPECT) in 30 patients (52.6%), and
      moderate or severe hypoperfusion in 27 (47.4%). Hypoperfusion was unrelated to
      age, duration of SLE or concentrations of anti-DNA antibodies and C3 and C4
      fractions. Patients with significant cerebral hypoperfusion had more active
      clinical disease (mean SLEDAI 13.92; SD 8.44 versus 4.56; SD 4.15) (Mann-Whitney,
      P < 0.005), more cumulative tissue damage (mean SLICC 2.66; SD 2.84 versus 1.03;
      SD 1.51) (Mann-Whitney, P = 0.035), and higher ESR values (mean 28.7; SD 22.5
      versus 17.7; SD 13.3) (Mann-Whitney, P = 0.023) than patients with normal SPECT
      studies. Significant cerebral hypoperfusion was related both to NPS
      manifestations present at the time of the study (17 of 27, 63% versus 3 of 30,
      10%) (OR: 15.3) and cumulative manifestations (19 of 27, 70.4% versus 8 of 30,
      26.7%) (OR: 6.5), whether mild (OR: 5.5) or severe (OR: 8.2). In conclusion,
      cerebral hypoperfusion detected by SPECT in patients with SLE is related to
      clinical activity (SLEDAI), cumulative tissue damage (SLICC) and concomitant or
      previous NPS manifestations.

PMID- 14667097
TI  - Antiphospholipid antibodies and antiphospholipid syndrome in 57 children and
      adolescents with systemic lupus erythematosus.
AB  - The presence of antiphospholipid (aPL) antibodies and antiphospholipid syndrome
      (APS) was researched in 57 children and adolescents with systemic lupus
      erythematosus (SLE). The frequency of aPL antibodies was 75.4% (anticardiolipin
      70.2% and lupus anticoagulant 29.1%). The positivity for these antibodies
      fluctuated during the course of the disease. No association was found between aPL
      antibodies and clinical or laboratory manifestations or the autoantibodies
      studied, nor with the activity or gravity of the SLE. APS was diagnosed in 14% of
      the cases (eight patients), on average three years after the diagnosis of SLE.
      Four patients had arterial thrombosis (stroke, three; transient ischaemic attack,
      one; amaurosis fugax, two; renal, one), one presented with deep vein thrombosis
      (DVT) and three had involvement of small calibre vessels (osteonecrosis, two;
      transverse myelitis, one). Recurrences were observed in three of the eight cases
      (37.5%), with a mean interval of 13 months between the events. The presence of
      APS was associated with haemolytic anaemia, leukopenia, thrombocytopenia,
      coagulation abnormalities, ischaemic cerebrovascular accidents, amaurosis fugax,
      osteonecrosis and interstitial pneumonitis. A negative association was observed
      between APS and the presence of anti-Ro antibodies.

PMID- 14667098
TI  - Poor prognosis of end-stage renal disease in systemic lupus erythematosus: a
      cohort of Chinese patients.
AB  - We studied the clinical course of 26 systemic lupus erythematosus (SLE) patients
      who started regular dialysis at our hospital and whose stay exceeded a three
      month duration in order to investigate the long-term prognosis in a Chinese
      cohort. Clinical and serological activities of lupus before and after dialysis
      were analysed. To compare the long-term survival rate, controls were set using 78
      age-matched end-stage renal disease (ESRD) patients who did not have SLE or
      diabetes mellitus and entered the chronic dialysis program at a similar period
      with SLE dialysis patients. There was a significant decrease in clinical lupus
      activity after starting regular dialysis (P < 0.05); however, the serological
      activity remained the same. The five-and ten-year survival rates were
      significantly lower in the SLE patients (73 and 38% in the SLE group versus 95
      and 88% in the non-SLE group, P < 0.05). SLE patients had a 4.3-times higher risk
      of death than non-SLE patients (P < 0.05, 95% confidence interval, 1.2-15.2).
      Also, the deceased SLE patients had persistent lower serum levels of complement
      3. SLE patients with ESRD remain clinically quiescent despite persistent
      serological abnormalities and have a worse prognosis than other uremia patients
      in the Chinese population.

PMID- 14667099
TI  - Testing for anti-nucleosome antibodies in daily practice: a monocentric
      evaluation in 1696 patients.
AB  - The objective was to report our experience of the detection of anti-nucleosome
      (anti-Nuc) antibodies (Ab) in a large series of consecutive patients, and to
      compare these results with those of anti-nuclear and anti-dsDNA Ab. In total,
      1696 consecutive patients with suspected or confirmed autoimmune disease were
      tested over a two-year period. The biological investigation included detection of
      anti-nuclear, anti-dsDNA and anti-Nuc Ab. Among 1696 sera, 382 (23%) were
      negative for all Ab tested (anti-nuclear, anti-dsDNA and anti-Nuc) and 1314 (77%)
      were positive for at least one Ab. Anti-Nuc Ab were positive in 350/1314
      patients. In this group, 249/350 (71%) also had positive anti-nuclear and anti
      dsDNA, 97/350 (28%) had only positive anti-nuclear Ab without anti-dsDNA Ab and
      4/350 (1%) had both anti-dsDNA and anti-Nuc Ab without anti-nuclear Ab. No
      patient had 'isolated' anti-Nuc Ab. Clinical data were available for 307/350 anti
      Nuc positive patients. Systemic lupus erythematosus (SLE) was diagnosed in
      240/307 (78%) patients, including 43 SLE patients with negative anti-dsDNA Ab. In
      conclusion, this study extends the relevance of anti-Nuc Ab to routine use for
      the diagnosis of connective tissue diseases, mainly anti-dsDNA Ab negative SLE.

PMID- 14667100
TI  - Synthetic CpG oligodeoxynucleotides accelerate the development of lupus nephritis
      during preactive phase in NZB x NZWF1 mice.
AB  - The effect of synthetic CpG-oligodeoxynucleotides (CpG-ODN) on the development of
      lupus nephritis during preactive phase (within seven months of age) in autoimmune
      lupus NZB x NZWF1 (B/WF1) mice was examined. Treatment of CpG-ODN was started at
      the age of 2.75 months and continued until 6.25 months. Overt disease began at
      the age of six months and progressed linearly at the age of 6.75 months in CpG
      ODN-treated, but not control ODN-treated (control) groups. Also compared to
      control group, CpG-ODN-treated mice exhibited a severe glomerulonephritis (GN),
      with prominent deposits of IgG2a and C3, which paralleled increased titre of
      IgG2a type anti-nuclear antibody in the blood. Among several cytokines
      (interleukin, IL-6, IL-4, IL-1alpha, IL-10, interferon-gamma and tumor necrosis
      factor-alpha) in blood, IL-6 production paralleled the development of lupus
      nephritis. The present study suggests that CpG-ODN may enhance IL-6 production.
      The role of IL-6 in the development of GN will be discussed.

PMID- 14667101
TI  - The heterogeneity of neuropsychiatric systemic lupus erythematosus is reflected
      in lack of association with cerebrospinal fluid cytokine profiles.
AB  - The objective was to study the occurrence of autoantibodies and cytokines in
      serum and cerebrospinal fluid (CSF) in neuropsychiatric systemic lupus
      erythematosus (NPSLE). In total, 28 consecutive patients with NPSLE and 16
      systemic lupus erythematosus (SLE) patients without neuropsychiatric involvement
      (non-NPSLE) were studied. IFN-alpha, IL-6, IL-10, soluble terminal complement
      complex (TCC), anti-ribosomal P protein antibodies (anti-P) and anti-cardiolipin
      antibodies (aCL) were measured in serum and CSF by immunoassays. Analyses of
      white blood cell differential count, CSF-albumin/serum-albumin ratio, IgG-index
      in CSF and isoelectric focusing in serum and CSF were also performed. CSF
      specimens from 23 healthy individuals were used as controls. IFN-alpha was
      elevated in the CSF of 5 of 28 NPSLE patients compared to three of 14 among the
      non-NPSLE patients. IL-6 was elevated in CSF in three of 26 NPSLE patients.
      Normal concentration of IL-10 was found in CSF in all 27 NPSLE-patients analysed.
      IFN-alpha in serum was elevated in 18 of 28 NPSLE patients. No distinct clinical
      phenotype was related to elevated cytokine concentration in serum or CSF. One
      patient with cerebral involvement complicated by progressive multifocal
      leukoencephalopathy displayed a very high IFN-alpha concentration in serum. High
      concentration of TCC was present in CSF from only one patient with systemic
      vasculitis and focal cerebral symptoms. In conclusion, the results of this study
      suggest that the diagnostic value of serum and CSF concentrations of IFN-alpha,
      IL-10, IL-6 and TCC is limited in unselected neuropsychiatric SLE, probably due
      to the heterogeneity of NPSLE pathogenesis.

PMID- 14667102
TI  - The two hit hypothesis in the antiphospholipid syndrome: acute ischaemic heart
      involvement after valvular replacement despite anticoagulation in a patient with
      secondary APS.
AB  - A patient with the antiphospholipid syndrome (APS), in whom a nonfatal myocardial
      infarction ensued after valvular heart replacement despite anticoagulation, is
      described. The report further stresses the role of concomitant risk co-factors in
      inducing thrombotic events and points out that cardiosurgery might represent a
      potential major risk for myocardial ischaemic damage in APS.

PMID- 14667103
TI  - Coexistence of lupus anticoagulant and acquired haemophilia in a patient with
      monoclonal gammopathy of unknown significance.
AB  - Acquired haemophilia or factor VIII (FVIII) deficiency, caused by FVIII inhibitor
      antibodies, is a very rare condition that commonly results in severe haemorrhagic
      complications. We report a case of acquired haemophilia presenting with a left
      calfnontraumatic haematoma. The patient was also found to have lupus
      anticoagulant (LAC). The simultaneous presence of LAC and FVIII inhibitor is
      exceedingly rare. The differentiation between these two conditions is crucial,
      because both result in a prolongation of the activated partial thromboplastin
      time test, which does not correct when mixed with the plasma of a normal control;
      however, the clinical manifestations range from thrombosis in the presence of LAC
      to massive haemorrhage with FVIII inhibitors.

PMID- 14667104
TI  - Systemic lupus erythematous with recurrent Guillain-Barre-like syndrome treated
      with intravenous immunoglobulins.
AB  - We report on an unusual case of a young African male with systemic lupus
      erythematosus who developed an acute, severe Guillain-Barre-like peripheral
      neuropathy associated with ascites. The illness appeared to respond dramatically
      to a short course of intravenous immunoglobulins. Eight months later he had
      recurrence of identical features. He required respiratory support. On this
      occasion there was no response to intravenous immunoglobulins or other measures
      and he died of sepsis after a protracted period of paralysis.

PMID- 14667105
TI  - Epidemiology of systemic lupus erythematosus in a northern Spanish population:
      gender and age influence on immunological features.
AB  - The present work was planned to research epidemiological and immunological
      features of systemic lupus erythematosus (SLE) in a Caucasian population from the
      north of Spain (Asturias). There is only one specialized immunology laboratory in
      this region where samples from all patients with a plausible or a firm diagnosis
      of SLE are referred for immunological analysis. Since 1992 we have reviewed
      registered data from samples submitted to the immunology laboratory with a firm,
      definitive diagnosis of SLE, based on the fulfillment of the American College of
      Rheumatology (ACR) criteria. We have constructed a database, which included 367
      SLE patients. The point prevalence was 34.12/ 100 000 (95% CI: 30.63-37.61/100
      000), whereas the incidence rate calculated during the last five years was
      2.15/100 000/year (95% CI: 1.76-2.54/100 000/year). The female/male ratio varied
      according to the age at diagnosis, being maximum (50 : 1) between 22 and 28
      years. The median age at diagnosis was significantly lower in females than in
      males. Immunological features also yielded sex and age peculiarities. The
      percentage of patients with anti-SSa antibodies yielded significant differences
      between males (18.6%) and females (34.6%). Anti-RNP and anti-Sm antibodies were
      more frequently present in childhood-onset patients, the difference with the
      oldest-onset group being statistically significant. Other analyses did not show
      significant differences, although, as a whole, we observed a trend towards a
      higher presence of autoantibodies related to an early disease onset.

PMID- 14667106
TI  - Periorbital oedema in systemic lupus erythematosus.

PMID- 14667107
TI  - Gender influence in suicidal behaviour of Polish adolescents.
AB  - OBJECTIVE: The aim of the study was to assess the prevalence and possible suicide
      attempts and ideation predictors in the school population of girls and boys in
      the city of Lodz. METHOD: A self-administered anonymous questionnaire was
      distributed to a representative (random) sample of 1663 students, aged 14-21.
      Boys and girls reporting no suicidal behaviour (NSB) constitute the control
      groups; the characteristics of these groups were compared to those of the groups
      with suicidal behaviour (SB), with focus on the associations between different
      variables and gender, separately for suicidal ideation (SI) and suicide attempts
      (SA). RESULTS: About 37% of girls and 25% of boys reported suicidal ideation and
      about 11% and 5%, respectively, suicide attempts. Boys were more likely to make
      multiple suicide attempts. The relation between SB and the history of psychiatric
      treatment was the same for both sexes. Boys with SB were significantly more often
      fascinated with death, and girls were significantly more often exposed to
      difficult family situations.

PMID- 14667108
TI  - Puberty, sexual development and eating disorders in adolescent outpatients.
AB  - This study examined puberty and psychosexual state in a clinical sample of
      adolescents attending for assessment because of eating disorders (ED). A total of
      57 adolescents (girls) aged 14-21 years (mean age 16.9 years) having either
      anorexia nervosa (AN) or bulimia nervosa (BN) were studied by semi-structured
      interviews and structured self-report questionnaires considering the timing of
      menarche, dating and attitudes to sexuality. The age at menarche did not differ
      statistically significantly between AN and BN. It was significantly lower in the
      BN group than in the normal population, but no statistically significant
      difference was found between the AN group and normal population. The general
      attitudes to sexuality were more negative in the AN group than in the BN group.
      In the AN group, there were also fewer dating experiences and interest in dating
      than in the BN group. After controlling for the effect of age, age at menarche
      and duration of ED, negative attitudes to sexuality and no dating experiences
      were still best predicted by AN. The results suggest different ways of coping
      with the developmental challenges in sexuality in AN and BN during adolescence.

PMID- 14667109
TI  - Sexually abused girls: patterns of psychopathology and exploration of risk
      factors.
AB  - This paper studies the patterns of psychopathology in sexually abused girls. It
      also explores some environmental risk factors for psychopathology including abuse
      characteristics and environmental experiences. The data are derived from the
      baseline assessment of 81 sexually abused girls referred to the London Child
      Sexual Abuse Psychotherapy Outcome Study (collaborative Tavistock and Maudsley
      project). Data about abuse were collected from the parent or foster parent using
      a standardised, semi-structured interview format. The girls' psychopathology was
      assessed using the Kiddie-SADS schedule. Widespread and serious psychopathology
      in sexually abused girls attending a psychotherapy clinic previously reported in
      a small-scale study was confirmed; so, too, was the extent of comorbidity and
      impairment of psychosocial functioning. Further, a significant association was
      found between children looked after away from home and high rates of Separation
      Anxiety Disorder. No such significant associations were found for Major
      Depressive Disorder nor impairment of functioning. Multivariate prediction
      analysis revealed that significant predictors of Major Depressive Disorder
      consisted of seriousness of abuse, the abuser not being a parent figure, and the
      abuse not being recent; the only significant predictor of Separation Anxiety
      Disorder was that the abuser was not a parent figure; finally, impairment of
      general functioning was strongly predicted by the greater seriousness of abuse
      and also by the abuser/s not being a parent figure. Theoretical explanations
      advanced for the reported associations have a sense of face validity: that girls
      abused by strangers will be at risk of developing Separation Anxiety Disorders;
      that serious sexual abuse is followed by the development of a Major Depressive
      Disorder and a high level of impairment of social functioning.

PMID- 14667110
TI  - Service utilisation by children with conduct disorders--findings from the GB
      National Study.
AB  - BACKGROUND: Children with conduct disorders and their families come into contact
      with a range of community and specialist agencies. METHODS: The aim of this study
      was to establish the lifetime service utilisation rates among children with
      conduct disorders from the Great Britain National Study (N = 10,438), and to
      examine the association between comorbid disorders, family and social factors,
      and service utilisation. The Development and Well-Being Assessment, a service
      checklist, and a battery of family and social functioning measures were used.
      RESULTS: The weighted prevalence of oppositional and conduct disorders was 5.4%.
      Within this group (N = 403), 241 (59.8%) had conduct disorder only, 79 (19.6%)
      comorbid emotional, 72 (17.9%) comorbid hyperkinetic, and 11 (2.7%) comorbid
      emotional and hyperkinetic disorders. These subgroups were compared on service
      utilisation with children with other psychiatric disorders (N = 351). Children
      with conduct disorders had significantly higher lifetime rates of utilisation of
      social and educational services than children with other psychiatric disorders.
      Contact with primary health, specialist health, and educational services was
      significantly associated with comorbid physical and psychiatric disorders. In
      contrast, contact with social services was associated with family discord and
      social sector tenancy. CONCLUSIONS: The findings are discussed in the context of
      organisation and co-ordination of health, other statutory, and non-statutory
      services, also taking into account previous research on interventions for
      children with conduct disorders and their families.

PMID- 14667111
TI  - Psychosocial impairment is significant in young referred children with and
      without psychiatric diagnoses and cognitive delays--applicability and reliability
      of diagnoses in face of co-morbidity.
AB  - "Subthreshold" psychiatric symptoms with clinically significant psychosocial
      impairment are a diagnostic problem. They may reduce the reliability of
      classifications and the communicative value of diagnostic descriptions when
      specific diagnostic categories cannot be applied. This study was undertaken in
      order to test the reliability and applicability of psychiatric diagnoses and
      psychosocial functioning scores as well as differences in psychosocial impairment
      in children referred to a neuropsychiatric outpatient unit. Two hundred and
      nineteen young children were diagnosed on all ICD-10 axes, except Axis V. First,
      reliability was tested with moderate to good results for psychiatric diagnoses
      (Kw = 0.55 and 0.73) and psychosocial impairment (ICC 1.1 = 0.71). Additional
      specification of the criteria for some of the Axis I diagnoses reduced the number
      of children with "subthreshold" conditions without a psychiatric diagnosis.
      Second, the severity of psychosocial impairment differed significantly between
      five psychiatric groups. Children with "subthreshold" conditions were as impaired
      psychosocially as those with hyperkinetic disorder and more so than children with
      emotional, social, and emotional and behavioural disorders. High chronological
      age, low IQ, low level of social skills, and psychiatric group (PDD) predicted
      psychosocial impairment. Third, the "subthreshold" group often had language
      problems (14 out of 18 children) unless they were mentally retarded.

PMID- 14667112
TI  - Psychopathy as a disorder of empathy.

PMID- 14667113
TI  - Central venous access catheters: radiological management of complications.
AB  - A great variety of central venous access devices such as tunneled and non
      tunneled central venous catheters (CVC) as well as port systems are implanted by
      interventional radiologists at an increasing rate. There are some possible
      immediate, early, and late complications related to the implantation technique,
      care, and maintenance of CVCs. This review will illustrate possible complications
      of CVCs and will discuss risk factors. Different strategies will be shown
      regarding the prevention and treatment of complications.

PMID- 14667114
TI  - Frequent embolization in peripheral angioplasty: detection with an embolism
      protection device (AngioGuard) and electron microscopy.
AB  - PURPOSE: To evaluate the deliverability and protection capabilities of an
      embolism protection filter in angioplasty of peripheral arteries. METHODS: The
      Angioguard emboli capture guidewire system was applied in 11 patients with
      femoropopliteal lesions (6 stenoses, 3 occlusions, 2 controls). Data on lesion
      crossing, flow deceleration and macroembolization were recorded. Filter membranes
      were evaluated with scanning electron microscopy (SEM). RESULTS: System delivery
      was successful in all patients. Primary lesion crossing was feasible in four of
      six stenoses; predilatation was required in two of six. Marked flow deceleration
      was recorded in six patients. Emboli next to the filter were detected in each
      patient with concentric plaques, but could not reliably be removed with the
      filter. Downstream macroembolization was also present in all patients with
      concentric stenoses, but in none with chronic occlusion. None of the patients had
      clinical signs of ischemia. SEM analysis demonstrated only small particles on
      control group filters and non-obliterating fibrinous conglomerates on filters
      used in chronic occlusion. Substantial obliteration was seen on several filters
      used in stenotic lesions. CONCLUSION: Microembolization of fibrin aggregates is a
      common incident in balloon angioplasty of femoropopliteal stenoses.
      Macroembolization occurred more frequently than previously reported. The use of
      embolism protection filters aided in the detection but not in the removal of
      larger emboli.

PMID- 14667116
TI  - Three-dimensional ultrasound-based navigation combined with preoperative CT
      during abdominal interventions: a feasibility study.
AB  - PURPOSE: Three-dimensional (3D) intraoperative ultrasound may be easier to
      interpret when used in combination with less noisy preoperative image data such
      as CT. The purpose of this study was to evaluate the use of preoperative image
      data in a 3D ultrasound-based navigation system specially designed for minimally
      invasive abdominal surgery. A prototype system has been tested in patients with
      aortic aneurysms undergoing clinical assessment before and after abdominal aortic
      stent-graft implantation. METHODS: All patients were first imaged by spiral CT
      followed by 3D ultrasound scanning. The CT volume was registered to the patient
      using fiducial markers. This enabled us to compare corresponding slices from 3D
      ultrasound and CT volumes. The accuracy of the patient registration was evaluated
      both using the external fiducial markers (artificial landmarks glued on the
      patient's skin) and using intraoperative 3D ultrasound as a measure of the true
      positioning of anatomic landmarks inside the body. RESULTS: The mean registration
      accuracy on the surface was found to be 7.1 mm, but increased to 13.0 mm for
      specific landmarks inside the body. CT and ultrasound gave supplementary
      information of surrounding structures and position of the patient's anatomy. Fine
      tuning the initial patient registration of the CT data with a multimodal CT to
      intraoperative 3D ultrasound registration (e.g., mutual information), as well as
      ensuring no movements between this registration and image guidance, may improve
      the registration accuracy. CONCLUSION: Preoperative CT in combination with 3D
      ultrasound might be helpful for guiding minimal invasive abdominal interventions.

PMID- 14667115
TI  - Extracranial carotid artery stenting in surgically high-risk patients using the
      Carotid Wallstent endoprosthesis: midterm clinical and ultrasound follow-up
      results.
AB  - The purpose of this study was to evaluate the feasibility, safety and midterm
      outcome of elective implantation of the Carotid Wallstent in patients considered
      to be at high surgical risk. In a prospective study, 54 carotid artery stenoses
      in 51 patients were stented over a 24-month period. Three patients underwent
      bilateral carotid artery stenting. Institutional inclusion criteria for invasive
      treatment of carotid occlusive disease (carotid endarterectomy or carotid artery
      stenting) are patients presenting with a 70% or more symptomatic stenosis and
      those with an 80% or more asymptomatic stenosis having a life-expectancy of more
      than 1 year. All patients treated by carotid artery stenting were considered at
      high risk for carotid endarterectomy because of a hostile neck (17 patients-
      31.5%) or because of severe comorbidities (37 patients--68.5%). No cerebral
      protection device was used. Of the 54 lesions, 33 (61.1%) were symptomatic and 21
      (38.8%) were asymptomatic. Follow-up was performed by physical examination and by
      duplex ultrasonography at 1 month, 6 months, 1 year and 2 years after the
      procedure. All 54 lesions could be stented successfully without periprocedural
      stroke. Advert events during follow-up (mean 13.9 +/- 5.7 months) were non-stroke
      related death in 6 patients (11.1%), minor stroke in 4 stented hemispheres
      (7.4%), transient ipsilateral facial pain in 1 patient (1.8%), infection of the
      stented surgical patch in 1 patient (1.8%) and asymptomatic instent restenosis in
      4 patients (7.4%). The percutaneous implantation of the Carotid Wallstent, even
      without cerebral protection device, appears to be a safe procedure with
      acceptable clinical and ultrasonographic follow-up results in patients at high
      surgical risk. But some late adverse events such as ipsilateral recurrence of non
      disabling (minor) stroke or instent restenosis still remain real challenging
      problems.

PMID- 14667117
TI  - Angioplasty or stenting in adult coarctation of the aorta? A retrospective single
      center analysis over a decade.
AB  - For over 11 years, endovascular treatment by angioplasty (PTA) alone or stenting
      of adult coarctation at a single center was evaluated. We retrospectively
      reviewed 28 consecutive patients (31 interventions), median age 25 years, treated
      between 1991 and 2002, 20 of whom had native coarctation. Thirteen patients had
      PTA alone (16 procedures) (10 "kissing balloon" angioplasty comprising 12
      interventions, and 3 single balloon angioplasty comprising 4 interventions) and
      15 patients were stented (15 procedures), including 6 secondary and 9 primary
      stents. There were no procedural or 30-day complications. For the whole group,
      the median follow-up was 6.6 years (range 1-10 years). In the PTA group, median
      follow-up was 9 years (range 3-10) and in the stenting group it was 3 years
      (range 1-5). There were 9 restenoses in the PTA group (6 after "kissing balloons"
      and 3 after single balloon) comprising 56% of the angioplasties (9/16
      procedures). There was 1 restenosis in the stenting group diagnosed at computed
      tomography (CT). The patient was clinically well. For the whole group there were
      significant reductions in systolic blood pressure (BP) (p = 0.0003), diastolic BP
      (p = 0.004) and number of drugs per patient (p = 0.045) at latest follow-up post
      treatment. Five patients discontinued therapy. Analysis of the groups revealed
      that the reduction of systolic and diastolic BP and number of drugs did not reach
      statistical significance in the PTA group but were significant in the stent
      group. The endovascular management of adult coarctation is safe. Stents may be
      more effective than PTA alone but longer-term follow-up of stents is required.

PMID- 14667118
TI  - Transluminally placed endovascular grafts for venous lesions in patients on
      hemodialysis.
AB  - This report summarizes a feasibility study of transluminally placed endovascular
      grafts (TPEG) using pre-expanded polytetrafluoroethylene (PTFE) to treat venous
      abnormalities in patients on hemodialysis. Seventeen patients with peripheral (n
      = 11) or central (n = 6) venous lesions were treated with TPEG devices. Covered
      Gianturco stents were used for the peripheral lesions and covered Palmaz stents
      were used for central lesions. Venous abnormalities included vascular rupture
      after balloon angioplasty or surgical thrombectomy (n = 4), stenosis associated
      with an aneurysm (n = 2) and occlusive disease and central stenoses not
      responsive to balloon angioplasty (n = 11). The mean primary patency period was
      37 days. The mean secondary patency period was 215 days. At 60, 180, and 360 days
      the primary and secondary patency rates were 40%, 32%, and 32%, and 70%, 55%, and
      39%, respectively. Follow-up studies have shown various outcomes of the implanted
      TPEG devices, which have included stenoses within the TPEG (n = 2), stenoses
      central to the TPEG (n = 1), stenoses peripheral to the TPEG (n = 3), acute
      thrombosis extending to the TPEG without a stenosis (n = 1), graft abandoned with
      patent TPEG (n = 6), and TPEG patent within primary patency period at last follow
      up (n = 4). The TPEG devices, made with pre-expanded PTFE, appear safe in the
      short term, do not prevent progressive dialysis access site failure, and need to
      be compared to PTA and endovascular stenting in a randomized prospective trial.

PMID- 14667119
TI  - Retrograde vs. antegrade puncture for infra-inguinal angioplasty.
AB  - This study was done to compare antegrade punctures with a retrograde puncture
      technique for infrainguinal angioplasty. A group of 100 consecutive patients (71
      men, 29 women) were randomized for antegrade puncture or retrograde puncture of
      the common femoral artery. Following retrograde puncture the guidewire was
      'turned' and placed into the superficial femoral artery. The time for gaining
      access, screening time, radiation dose, patient height, weight and complications
      were recorded. All patients were reviewed the day after the procedure and within
      3 months. Data from 46 patients (34 males and 12 females) in the retrograde group
      and 44 (28 males and 16 females) in the antegrade group were available for
      analysis. Mean procedure time, screening time, radiation dose, height and weight
      were 8.3 minutes (range 3-22), 2.1 minutes (0.3-6.5), 7950 mGy cm(-2) (820
      71250), 169 cm (149-204) and 79 kg (32-108) for retrograde puncture and 8 min (2
      60), 0.7 min (0.0-3.2), 1069 mGy cm(-2) (0-15400), 169 cm (152-186) and 75 kg (39
      125) for antegrade punctures, respectively. An average of 1.2 (1-2) punctures was
      required for retrograde and 1.75 (1-8) for antegrade. Seven small hematomas
      occurred with antegrade and three for retrograde puncture. Retrograde puncture is
      technically easier with a tendency to fewer complications but results in a higher
      radiation dose. This technique should be used in difficult patients at high risk
      of haematoma formation.

PMID- 14667120
TI  - Comparison of pain after uterine artery embolization using tris-acryl gelatin
      microspheres versus polyvinyl alcohol particles.
AB  - When compared in a uterine artery embolization (UAE) animal model, Embospheres
      (ES) (Biosphere Medical, Rockland, MA) were found to induce less uterine ischemia
      than polyvinyl alcohol (PVA) particles. Given this finding, we aimed to test the
      hypothesis that ES is associated with less pain after UAE than PVA in human
      patients. We performed retrospective analysis on data from 72 consecutive UAE
      patients, collected from a prospectively acquired database. Patient-controlled
      analgesia (PCA) pump-delivered morphine sulfate (MS) dosages were compared
      between patients who received ES versus PVA. Subjective pain scores (SPS) were
      also compared between the two groups. Secondary outcome measures, including
      embolic volume and clinical outcome data, were also collected. Linear regression
      and t-test statistical analyses were performed. Null hypotheses were rejected at
      the p < 0.05 level. Mean follow-up period in the PVA population was 178 days
      (range 28-426), versus 96 days (range 24-197) in the ES population. The mean MS
      doses used by ES and PVA patients were 37.2 (s.d. 23.5) versus 47.1 (s.d. 26.8),
      respectively. This difference was not significant (p > 0.15). Utilizing a
      standard 0-10 pain scale, the mean peak SPS for the ES and PVA groups were 5.58
      (s.d. 2.77) and 5.07 (s.d. 2.99), respectively. The difference was not
      significant. The mean amount of embolic material used in each ES and PVA patient
      was 4.86 cc (s.d. 3.01) and 3.52 cc (s.d. 1.63), respectively. The difference
      revealed a strong trend toward statistical significance (p = 0.05). There was one
      treatment failure in each group of patients. Within both patient samples, no
      significant correlation was found when comparing the volume of embolic used and
      subsequent MS dose. Despite a strong trend toward a significantly higher volume
      of ES used per patient, there is no subjective or objective difference in pain
      after UAE with ES when compared to PVA.

PMID- 14667121
TI  - Hyperthermia in the treatment of cholangiocarcinoma: development and testing of
      an endobiliary microwave device.
AB  - PURPOSE: The aim of this study was to create, perfect and test a hyperthermia
      balloon catheter for local treatment of cholangiocarcinoma. The device should
      induce hyperthermia in tumor tissue by acting locally in the bile duct lumen in
      contact with the tumor-infiltrated duct wall. In addition, it should exert tissue
      compression to cause an appreciable reduction in tumor microvasculature flow,
      thus improving thermal performance. METHODS: According to the design
      specifications, the working temperature range should allow the device to be used
      for hyperthermia therapy either in combination with radiation and/or chemotherapy
      (radio/chemo-sensitizing effect at 42-45 degrees C) or alone (induction of
      coagulation necrosis above 65 degrees C). The balloon serves as an anchoring
      system during treatment and as a functional element to induce tissue compression.
      In vitro mechanical evaluation of the pressure/volume relationship, with the
      balloon inside rigid walled conduits, was performed. The heating shape around the
      catheter tip was determined by egg-white heating tests (coagulation at about 65
      degrees C). Moreover, heating tests were carried out with explanted pig liver
      parenchyma. The temperature profile over time at different depths from the
      catheter axis was traced. RESULTS: Three prototypes were manufactured. Mechanical
      functional tests showed that a 14 Fr deflated diameter balloon was suitable for
      bile duct diameters up to 11 mm. Thermal egg-white tests produced 4 cm long, 3 cm
      in diameter ellipsoidal heating figures in 30 min. In the biological tissue tests
      a coagulated area of similar geometry and comparable volume was produced.
      CONCLUSION: The results of tests confirm the device's usefulness and versatility.

PMID- 14667122
TI  - In vivo evaluation of the effects of gravitational force (+Gz) on over-the-wire
      stainless steel Greenfield inferior vena cava filter in swine.
AB  - This study was done to determine the effect of exposure to gravitational force
      (acceleration stress) on in vivo over-the-wire stainless steel Greenfield
      inferior vena cava filters. Fifteen pigs underwent venous cut down and placement
      of a stainless steel Greenfield filter. A 4-week observation period simulated
      realistic convalescence and allowed sufficient time for epithelialization. Ten
      pigs were exposed to acceleration stress in a centrifuge (3G run for 15 sec
      followed by rest until return to baseline heart rate, then a 9G run for 15 sec),
      with inertial loading in a head-to-tail direction (+Gz). Fluoroscopy during
      acceleration stress allowed assessment for filter migration. Five pigs were not
      exposed to acceleration stress. AP and lateral abdominal radiographs were
      obtained at post-filter placement, convalescence, and centrifuge exposure to
      determine the position and integrity of the filter. All 15 IVCs were resected and
      evaluated for gross or histological injury to the vessel wall. IVC filter
      placement was technically successful in all 15 pigs. Radiographic measurements
      were limited secondary to differences in pig positioning. Fluoroscopy showed no
      filter migration. All filters were securely attached to the vena cava by the
      hooks without gross evidence of perforation or hemorrhage. There were varying
      degrees of fibroplasia involving the hooks and tip of the filters in both the
      control and experimental groups. Histologically, there was evidence of prior
      hemorrhage at the level of the hooks, which was similar between the control and
      experimental groups. It is concluded that Greenfield filter position and vena
      caval integrity at the implantation site is unaffected by high acceleration
      stress.

PMID- 14667123
TI  - Pancreatitis-induced extrahepatic portal vein stenosis treated by percutaneous
      transhepatic stent placement.
AB  - One month after onset of an acute biliary pancreatitis, a 75-year-old man
      developed refractory ascites. Duplex ultrasound and CT scan revealed a focal
      stenosis of the extrahepatic portal vein as confirmed by transhepatic direct
      portography. In the same session, this stenosis, responsible for symptomatic
      prehepatic portal hypertension, was successfully dilated and stented and
      afterwards a residual pressure gradient of 1 mmHg over the stented segment was
      measured. One week after the stenting procedure the patient was free of ascites
      and control physical and biochemical examination one year later is completely
      normal.

PMID- 14667124
TI  - The role of preoperative TIPSS to facilitate curative gastric surgery.
AB  - The use of TIPSS to facilitate radical curative upper gastrointestinal surgery
      has not been reported. We describe a case in which curative gastric resection was
      performed for carcinoma of the stomach after a preoperative TIPSS and
      embolization of a large gastric varix in a patient with portal hypertension.

PMID- 14667125
TI  - Fatal complications after self-expandable metallic stent placement for inferior
      vena cava syndrome.
AB  - We present the case of a 71-year-old man with inferior vena cava syndrome due to
      metastatic lymph nodes from hepatocellular carcinoma with serious complications
      that were strongly suspected to result from rapid changes in hemodynamics after
      self-expandable metallic stent placement.

PMID- 14667126
TI  - Dissecting aneurysm of the superior mesenteric artery successfully treated by
      endovascular stent-graft placement.
AB  - Spontaneous and isolated dissecting aneurysm of the superior mesenteric artery is
      a rare event that has been successfully treated by surgery in several reported
      cases. To our knowledge, we present the first case of a patient with spontaneous
      and isolated dissecting aneurysm of the superior mesenteric artery that was
      successfully treated by endovascular stent-graft placement.

PMID- 14667127
TI  - Percutaneous closure of an iatrogenic puncture of the aortic arch.
AB  - We report on the management of a rare complication of a vascular sheath being
      placed inadvertently in the aorta rather than in the venous system following
      thrombolytic therapy administration in a patient presenting with an acute
      myocardial infarction and complete heart block.

PMID- 14667128
TI  - Successful angioplasty of a superficial femoral artery stenosis caused by a
      suture-mediated closure device.
AB  - We report the successful angioplasty of an acute arterial narrowing after suture
      mediated closure (SMC) of a femoral arterial puncture. A 75-year-old woman
      underwent a cerebral arteriogram via a right common femoral artery puncture. The
      arteriotomy site was closed with a SMC device. Four days after placement the
      patient complained of pain in her right calf after walking. An arteriogram 7 days
      after SMC showed a severe focal stenosis at the origin of the superficial femoral
      artery involving the presumed puncture site. The lesion was successfully treated
      with balloon angioplasty. The patient at 6 months was asymptomatic.

PMID- 14667129
TI  - Radiofrequency ablation treatment in proximity to the gallbladder without
      subsequent acute cholecystitis.
AB  - Initial reports have suggested that proximity of liver tumors to the gallbladder
      may increase the risk for cholecystitis after radiofrequency ablation. A colon
      adenocarcinoma metastasis to the liver in contact with the gallbladder was
      successfully treated with radiofrequency ablation without subsequent
      cholecystitis.

PMID- 14667130
TI  - Intrahepatic regional portal blood flow modulation using percutaneous US
      monitoring portal vein compression during radiofrequency thermal ablation.

PMID- 14667131
TI  - Thyroid hormones: beneficial or deleterious for bone?
AB  - The mechanism of action as well as the clinical effects of thyroid hormones on
      bone has been of interest for more than a century. With the appearance of new
      treatment modalities for thyroid function disorders, the accompanying alterations
      in bone metabolism appeared to be rare. However, the introduction of new
      diagnostic tools, such as osteodensitometry and biochemical bone markers, has
      changed our view since they were able to show smaller but important changes in
      bone mineral metabolism associated with thyroid function disorders. Now, we know
      that hyperthyroidism is associated with an increased life-time risk for
      fractures, even after achieving euthyroidism. This fact may play an important
      role in the higher mortality rate among previously hyperthyroid patients later in
      life. Subclinical hyperthyroidism may also affect bone density, however, its
      effect on fracture rate remains to be established. The lack of thyroid hormones
      will alter normal growth during childhood. Adult hypothyroid patients tend to
      exhibit higher than normal bone density. Despite rather increased bone quantity,
      hypothyroidism is accompanied with increased fracture risk before and after
      diagnosis. The effect of thyroid hormone treatment on bone tissue is somewhat
      controversial. Nevertheless, only patients with suppressed thyroid-stimulating
      hormone (TSH) appear to loose bone and have higher fracture incidence, whereas
      patients with a TSH level in the normal range seem to have similar bone mineral
      content and fracture rate as euthyroid subjects. In summary, most of thyroid
      function disorders may result in reduced bone density and/or increased fracture
      rate that should be taken into consideration at clinical evaluation.

PMID- 14667132
TI  - Osteoprotegerin levels in primary hyperparathyroidism: effect of
      parathyroidectomy and association with bone metabolism.
AB  - The effect of parathyroid hormone (PTH) on the production of osteoprotegerin
      (OPG) remains controversial. Most in vitro studies indicate that PTH decreases
      OPG secretion by the osteoblast, but in vivo observations are conflicting. In
      primary hyperparathyroidism (PHPT), hypersecretion of PTH leads to enhanced bone
      resorption and formation with increased risk of fracture. Patients with PHPT are
      cured by surgery, resulting in normalization of PTH levels and bone metabolism,
      but the concomitant effects on OPG production are not known. The hypothesis of
      the present study was that the circulating level of OPG is diminished in patients
      with PHPT and increases with successful parathyroidectomy. We also speculated
      that serum OPG may determine the magnitude of bone loss up to the time of
      surgery. In the present study, 20 patients (17 women and 3 men, mean age 62 y)
      with PHPT who were candidates for surgical cure were examined before and 12
      months after surgery. Bone turnover markers decreased and BMD increased
      significantly after surgery. Serum OPG did not correlate with PTH before surgery
      (r = 0.07, P = 0.77) and was not affected by parathyroidectomy (P = 0.79). After
      normalization of PTH, bone formation markers showed significant (P1NP) and near
      significant (osteocalcin) correlations with serum OPG. In conclusion, serum OPG
      is not decreased in patients with PHPT, nor is serum OPG to any demonstrable
      extent regulated by PTH pre- or postoperatively.

PMID- 14667133
TI  - Dual hip bone mineral density in postmenopausal women: geometry and effect of
      physical activity.
AB  - The objectives of this study were to (1) obtain both femoral neck strength (FNS)
      and hip axis length (HAL) values from left and right femurs (regardless of hip
      dominance) measured by DXA and evaluate their relationship with BMD of all hip
      regions including total hip, (2) determine if there is a difference between
      dominant and nondominant hip BMD in any of the hip regions, and (3) determine how
      physical activity influences hip BMD. Participants were 136, generally healthy
      Caucasian women (57.4-88.6 years). BMD was measured by DPX-MD. Past and present
      activity was assessed by the Allied Dunbar National Fitness Survey for older
      adults and normal/brisk walking pace was measured in a straight hallway. FNS
      analysis uses femoral geometry to calculate stresses at the femoral neck for two
      loading conditions: Safety Factor Index (SF) indicates risk of fracture for
      forces generated during a one-legged stance, and Fall Index (FI) indicates risk
      of fracture for forces generated during a fall on the greater trochanter. Simple
      and multiple regression analyses were used to determine predictive ability of
      HAL, SF, and FI for respective hip BMD values. There was no statistical
      difference in BMD between two hips in any of the measured regions, however, the
      nondominant hip correlated better with other skeletal sites. Subjects with a
      faster normal walking speed had higher neck BMD in the nondominant hip, 0.832 +/-
      0.12 vs. 0.791 +/- 0.10 g/cm2 (P < 0.05). Longer HAL of the left hip was
      negatively related to neck, trochanter, shaft, and total hip BMD. FI was
      significantly associated with all sites of the hip BMD, while SF was associated
      only with neck and wards BMC (P < 0.05). In summary: (1) a longer HAL is
      associated with lower BMD and a higher FI with higher BMD, (2) it might be
      sufficient to measure BMD in only the nondominant hip, and (3) walking at a
      faster pace may positively benefit femoral neck BMD. Therefore, it appears that
      HAL, SF, and FI all play important roles in estimating fracture risk and should
      be assessed along with BMD when using DXA.

PMID- 14667134
TI  - Architectural measures of the cancellous bone of the mandibular condyle
      identified by principal components analysis.
AB  - As several morphological parameters of cancellous bone express more or less the
      same architectural measure, we applied principal components analysis to group
      these measures and correlated these to the mechanical properties. Cylindrical
      specimens (n = 24) were obtained in different orientations from embalmed
      mandibular condyles; the angle of the first principal direction and the axis of
      the specimen, expressing the orientation of the trabeculae, ranged from 10
      degrees to 87 degrees. Morphological parameters were determined by a method based
      on Archimedes' principle and by micro-CT scanning, and the mechanical properties
      were obtained by mechanical testing. The principal components analysis was used
      to obtain a set of independent components to describe the morphology. This set
      was entered into linear regression analyses for explaining the variance in
      mechanical properties. The principal components analysis revealed four
      components: amount of bone, number of trabeculae, trabecular orientation, and
      miscellaneous. They accounted for about 90% of the variance in the morphological
      variables. The component loadings indicated that a higher amount of bone was
      primarily associated with more plate-like trabeculae, and not with more or
      thicker trabeculae. The trabecular orientation was most determinative (about 50%)
      in explaining stiffness, strength, and failure energy. The amount of bone was
      second most determinative and increased the explained variance to about 72%.
      These results suggest that trabecular orientation and amount of bone are
      important in explaining the anisotropic mechanical properties of the cancellous
      bone of the mandibular condyle.

PMID- 14667135
TI  - Systemic effects on bone healing of a new hyaluronic acid-like bacterial
      exopolysaccharide.
AB  - Critical Size Defect (CSD) technique was used to evaluate the systemic activities
      on bone regeneration capacity of a newly discovered hyaluronic acid-like
      exopolysaccharide synthesized by a bacteria originating from a deep sea
      hydrothermal vent. Some systemic effects were previously detected on earlier
      experiments. A 5 mm diameter hole was made on each parietal bone of male rats.
      The right hole was filled with 0.5 mg of a new bacterial exopolysaccharide
      referenced HE 800, while the left hole remained free of any treatment. After 21
      days, the holes and surrounding tissues were examined by direct examination, X
      rays, and histological staining. Using HE 800, bone healing was almost complete
      after only 21 days in the treated hole and always complete in the control side by
      some systemic effect. Neovascularization was also observed along with an
      organized trabecular bone on both sides. No abnormal bone growth or conjunctival
      abnormalities were noticed. At the end of the experiment, 90.1% ( +/- 5.2) bone
      healing (n = 20) was observed on the treated side; conversely, the control side
      animals demonstrate an amazing healing 100% (+/- 0.5) by a systemic effect.

PMID- 14667136
TI  - A CAG repeat polymorphism in the androgen receptor gene is associated with
      reduced bone mass and increased risk of osteoporotic fractures.
AB  - Osteoporosis is a common disease with a strong genetic component. Hypogonadism
      results in low bone mass and it increases significantly the risk of osteoporosis
      in both sexes. The estrogen and androgen receptor genes are therefore strong
      candidates for mediating the genetic influence on bone mass and risk of
      osteoporosis. A CAG repeat in the first exon of the androgen receptor (AR) is
      associated with reduced transcriptional activity of the AR. We therefore examined
      whether this CAG repeat polymorphism is associated with changes in bone mass and
      risk of osteoporotic fractures in 284 osteoporotic patients with vertebral
      fractures and 327 normal individuals. The number of CAG repeats varied between 13
      and 30 in men and between 7 and 34 in women. The short and long alleles comprised
      19.2 +/- 2.5 and 19.0 +/- 2.3 repeats (ns) and 22.7 +/- 2.4 and 21.9 +/- 2.4 (P <
      0.01) in women with vertebral fractures and normal women, respectively. This
      difference was also reflected in the average number of CAG repeats: 21.0 +/- 2.0
      in osteoporotic women vs. 20.5 +/- 2.0 in normal women (P < 0.05). 54.8% of women
      with osteoporotic fractures vs. 45.9% of normal women had average number of CAG
      repeats of 21 and more (chi2 = 3.11, P = 0.08). Logistic regression analyses
      revealed that both the average number of CAG repeats and the length of the long
      allele were significant predictors of osteoporotic fractures in women (P < 0.05
      and P < 0.01, respectively). Men with vertebral fractures had 20.0 +/- 2.8 CAG
      repeats compared with 20.7 +/- 2.5 CAG repeats in normal men (ns). Linear
      regression analysis revealed that the length of the long allele was negatively
      correlated with BMD of the lumbar spine (P < 0.05) and femoral neck (P < 0.05) in
      women. In men, linear regression analyses demonstrated that BMD of the lumbar
      spine (P < 0.05), femoral neck (P < 0.05) and total hip (P < 0.05) was positively
      correlated with length of the CAG repeat polymorphism. In conclusion, we have
      demonstrated that the CAG repeat polymorphism in the first exon of the AR gene is
      associated with reduced bone mass and increased risk of osteoporotic fractures in
      women.

PMID- 14667137
TI  - No evidence for linkage and/or association of human alpha2-HS glycoprotein gene
      with bone mineral density variation in Chinese nuclear families.
AB  - Osteoporosis is an important health problem in the world. Alpha2-HS glycoprotein
      (AHSG) is involved in bone formation and metabolism and has been considered as an
      important candidate gene for osteoporosis. In this study, we simultaneously
      tested linkage and/or association of the AHSG gene with the variation of bone
      mineral density (BMD), an important risk factor for osteoporosis. A sample of
      1,260 subjects from 401 Chinese nuclear families (including both parents and
      their daughters) were studied. The daughters' ages ranged from 20 to 45 years.
      All the subjects were genotyped by PCR-RFLP (polymerase chain reaction
      restriction fragment length polymorphism) at polymorphic Sac I site inside the
      exon 7 of the AHSG gene. This polymorphism involves a nucleotide substitution of
      C to G at the middle nucleotide of the codon at amino acid position 238,
      resulting in the replacement of threonine (ACC) with serine (AGC). BMD was
      measured at the lumbar spine and hip region by dual-energy X-ray absorptiometry
      (DXA). Using the QTDT (quantitative trait transmission disequilibrium test), we
      found no significant results for association or linkage between the AHSG gene and
      BMD variation at the spine or hip. Our data provided no evidence to support the
      AHSG gene as a quantitative trait locus (QTL) for the BMD variation in a Chinese
      population.

PMID- 14667138
TI  - Targeted overexpression of vitamin D receptor in osteoblasts increases calcium
      concentration without affecting structural properties of bone mineral crystals.
AB  - Increased cross-sectional area and strength of long bones has been observed in
      transgenic mice with 2-fold (OSV9) and 3-fold (OSV3) elevation of osteoblast
      vitamin D receptor (VDR) levels. In the present study, mineralization density
      distributions, including typical calcium content (Ca(Peak)) and homogeneity of
      mineralization (Ca(Width)) of femoral bone and growth plate cartilage, were
      determined by quantitative backscattered electron imaging (qBEI). Fourier
      transform infrared (FTIR) microspectroscopy was used to examine mineral content,
      collagen and crystal maturation, and scanning small angle X-ray scattering
      (scanning-SAXS) for studying mineral particle thickness and alignment. In
      addition, X-ray diffraction (XRD) of distal tibiae revealed mineral particle c
      axis size. In trabecular bone, the increase in Ca(Peak) was significant for both
      OSV9 (+ 3.14%, P = 0.03) and OSV3 (+ 3.43%, P = 0.02) versus controls with 23.61
      +/- 0.45 S.D. wt% Ca baseline values. In cortical bone, Ca(Peak) was enhanced for
      the OSV3 mice (+ 1.84%, P = 0.02) versus controls with 26.61 +/- 0.28 S.D. wt%
      Ca, and OSV9 having intermediate values. Additionally, there was significantly
      increased homogeneity of mineralization as denoted by a reduction of Ca(Width) (
      8.4%, P = 0.01) in primary spongiosa. FTIR microspectroscopy, with the exception
      of an increased collagen maturity in OSV3 trabecular bone (+ 9.9%, P = 0.02),
      XRD, and scanning-SAXS indicated no alterations in the nanostructure of
      transgenic bone. These findings indicate that elevation of osteoblastic vitamin D
      response led to formation of normal bone with higher calcium content. These
      material properties, together with indications of decreased bone resorption in
      secondary spongiosa and increased cortical periosteal bone formation, appear to
      contribute to the improved mechanical properties of their long bones and suggest
      an important physiological role of the vitamin D-endocrine system in normal bone
      mineralization.

PMID- 14667139
TI  - Local anabolic effects of growth hormone on intact bone and healing fractures in
      rats.
AB  - The local effects of rat growth hormone (rGH) injected at the surfaces of intact
      tibial diaphyses and healing tibial diaphysial fractures were investigated in 10
      month-old female rats. Intact diaphysial bones: rats were injected daily for 14
      days with vehicle, 2 microg rGH, or 20 microg rGH at the surface of the right
      tibial diaphysis. After 10 days of injection the animals were labeled with
      calcein. At the rGH-injected location, increased external diaphysial bone
      dimensions and increased calcein-labeled area were seen, and the responses to rGH
      were dose dependent. The new bone formed at the periosteal surface was woven
      bone. At the opposite left tibia, no systemic effect of rGH was found. rGH did
      not influence body weight changes during the treatment, or muscle mass or serum
      IGF-I at the end of the treatment. Healing diaphysial fractures: a closed
      fracture was made in the right tibial diaphysis, and stabilized by medullary
      nailing. The fractures were tested after 21 days and 98 days of healing. During
      the first 21 days of healing, all rats were injected daily with either vehicle or
      20 microg rGH at the surface of the fracture line. In the 21-day healing rGH
      group, ultimate load, ultimate stiffness, external callus dimensions, and
      external callus volume of the fractures were increased. rGH did not affect body
      weight changes during this healing period or serum IGF-I at the end of the
      healing period. In the 98-day healing rGH group, ultimate load was still
      increased compared with the vehicle group, although a ninefold increase took
      place in the vehicle group between days 21 and 98 of healing. External callus
      dimensions of the fractures were increased in the rGH group, whereas body weight
      changes during the healing period were not affected.

PMID- 14667140
TI  - Regulation of osteoclasts by calcitonin and amphiphilic calcitonin conjugates:
      role of cytosolic calcium.
AB  - The peptide hormone calcitonin is a potent inhibitor of osteoclastic resorption,
      but it is unstable and poorly absorbed following oral administration. Conjugates
      of salmon calcitonin covalently linked to low-molecular-weight amphiphilic
      polymers show improved stability and absorption. The purpose of this study was to
      investigate the biological activity of these conjugates in vitro using rat
      osteoclasts and HEK-293 cells transfected with the C1a isoform of the calcitonin
      receptor. Salmon calcitonin or its conjugates (10 pM-10 nM) caused rapid arrest
      of osteoclast membrane ruffling and subsequent retraction. The same amphiphilic
      polymer attached to an unrelated protein had no effect on osteoclast morphology
      or motility. Since calcitonin-induced retraction of osteoclasts is thought to be
      mediated by Ca2+ signaling, we investigated the effects of calcitonin and its
      conjugates on cytosolic free Ca2+ concentration ([Ca24]i). In HEK-293 cells
      transfected with the calcitonin receptor, these agents induced transient
      elevations of [Ca2+]i. However, the rise of [Ca2+]i in HEK-293 cells occurred at
      concentrations 100-1000-fold higher than those required to elicit osteoclast
      retraction. To investigate the role of Ca2+ in osteoclast retraction, we
      preloaded cells with BAPTA to buffer changes in [Ca2+]i. BAPTA decreased the
      initial rate of calcitonin-induced osteoclast retraction, but it did not affect
      the degree of retraction 2-3 hours following calcitonin, indicating that
      retraction is mediated primarily by Ca(2+)-independent processes. We conclude
      that calcitonin conjugates cause osteoclast retraction and [Ca2+]i signaling in a
      manner similar to that elicited by calcitonin. Thus, orally bioavailable
      calcitonin conjugates show potential for use as antiresorptive agents.

PMID- 14667141
TI  - Induction of p53 expression and function by estrogen in osteoblasts.
AB  - While estrogen's role in maintaining bone health relates to its action on
      osteoclasts, not much is presently known about the role of estrogen with respect
      to osteoblasts. Our laboratory is involved in studying the function of the p53
      tumor suppressor gene in osteoblast differentiation. This study was therefore
      designed to understand the role of estrogen in osteoblast growth and
      differentiation and its effect on p53 function. ROS 17/2.8 cells, stably
      transfected with a construct containing multiple copies of a p53 response element
      fused to a chloramphenicol acetyl transferase (CAT) gene, were used to monitor
      wild-type p53 activity. Maximal p53 activity was observed when E2 was given at
      concentrations between 10(-12) and 10(-15) M. This increase in p53 activity was
      due to a change in transcription and peaked at about 16 hours after treatment. An
      increase in p53 activity was followed by an increase in expression of p53
      regulated genes p21 and mdm2. This increase in p53 activity was partially
      inhibited by inclusion of estrogen antagonist ICI 182,780. Bone- specific markers
      osteocalcin and alkaline phophatase increased after treatment with E2, as did
      changes in estrogen receptors alpha and beta. Upregulation of osteocalcin was
      reduced when cycloheximide was added to E2, suggesting the presence of
      intermediates in the enhancement of osteocalcin gene transcription. These
      findings suggest that E2 can directly mediate an increase in p53 expression and
      function. The relevance of this to osteoblast differentiation is discussed.

PMID- 14667142
TI  - Coexpression of bone sialoprotein (BSP) and the pivotal transcriptional regulator
      of osteogenesis, Cbfa1/Runx2, in malignant melanoma.
AB  - Bone sialoprotein (BSP) is a member of the SIBLINGS family, normally restricted
      to the skeleton, but it has been shown to be ectopically expressed in some human
      invasive carcinomas. BSP expression in human cancer was initially associated with
      the ability of BSP-expressing tumors to metastasize to bone, although the
      mechanism whereby BSP expression should facilitate homing of cancer cells to the
      bone marrow environment has remained unexplained. More recently, clinical and
      experimental data have converged in highlighting a potential link between BSP
      expression and tumor invasiveness in general. We show here that human malignant
      melanoma cells express BSP in vivo as a function of extent of local invasion, and
      that expression of BSP mRNA and protein in melanoma cells is associated with the
      expression of the transcriptional regulator of osteogenic cell differentiation,
      Cbfa1/Runx2. It has been well established that expression of Cbfa1/Runx2 in the
      mouse is normally restricted to bone-forming cells. In the mouse, Cbfa1/Runx2
      dictates osteogenic differentiation of mesodermal cells by regulating bone
      specific genes. Since it also regulates expression of at least two matrix
      metalloproteases implicated in tumor invasion and metastasis (collagenase 3,
      membrane type 1 matrix metalloproteinase), we propose that the relationship
      between BSP expression and an invasive behavior in human epithelial cancer cells
      may be rooted in a common transcriptional control exerted by Cbfa1.

PMID- 14667143
TI  - Differential effects of calmodulin and protein kinase C antagonists on bone
      resorption and acid transport activity.
AB  - Tamoxifen inhibits bone resorption by disrupting calmodulin-dependent processes.
      Since tamoxifen inhibits protein kinase C in other cells, we compared the effects
      of tamoxifen and the PKC inhibitor, bis indolylmaleimide II (bIM), on bone
      resorption and acid transport activity in isolated membrane vesicles. Bis
      indolylmaleimide inhibited bone resorption 50% with an IC50 approximately 3
      microM, as well as acid transport activity in a concentration -dependent manner
      with an IC50 of approximately 0.4 IM. The IC50 of bIM for inhibiting acid
      transport activity was similar to that of calmodulin antagonists. The potassium
      ionophore, valinomycin, failed to restore bIM or tamoxifen-dependent inhibition
      of acid transport, suggesting that bIM and tamoxifen both inhibit H(+)-ATPase
      activity. Half maximal inhibitory concentrations of tamoxifen and bIM were not
      additive in acid transport assays, suggesting different sites of action.
      Furthermore, exogenous calmodulin blocked tamoxifen, but not bIM, -dependent
      inhibition of acid transport. We also compared the effects of tamoxifen and bIM
      on phosphorylation of proteins in isolated membrane fractions as determined by
      32P incorporation and autoradiography. Tamoxifen had no effect on protein
      phosphorylation in contrast to bIM, which inhibited phosphorylation of eight
      proteins with different apparent kinetics. The data suggest that, while tamoxifen
      and bIM both affect H(+)-ATPase activity, the mechanisms of action are different.

PMID- 14667145
TI  - The suprachiasmatic nucleus: a clock of multiple components.
AB  - Although impressive progress has been made in understanding the molecular basis
      of pacemaker function in the suprachiasmatic nucleus (SCN), fundamental questions
      about cellular and regional heterogeneity within the SCN, and how this
      heterogeneity might contribute to SCN pacemaker function at a tissue level, have
      remained unresolved. To reexamine cellular and regional heterogeneity within the
      SCN, the authors have focused on two key questions: which SCN cells are
      endogenously rhythmic and/or directly light responsive? Observations of
      endogenous rhythms of electrical activity, gene/protein expression, and protein
      phosphorylation suggest that the SCN in mammals examined to date is composed of
      anatomically distinct rhythmic and nonrhythmic components. Endogenously rhythmic
      neurons are primarily found in rostral, dorsomedial, and ventromedial portions of
      the nucleus; at mid and caudal levels, the distribution of endogenously rhythmic
      cells in the SCN has the appearance of a "shell." The majority of nonrhythmic
      cells, by contrast, are located in a central "core" region of the SCN, which is
      complementary to the shell. The location of light-responsive cells, defined by
      direct retinohypothalamic input and light-induced gene expression, largely
      overlaps the location of nonrhythmic cells in the SCN core, although, in hamsters
      and mice light-responsive cells are also present in the ventral portion of the
      rhythmic shell. While the relative positions of rhythmic and light-responsive
      components of the SCN are similar between species, the precise boundaries of
      these components, and neurochemical phenotype of cells within them, are variable.
      Intercellular communication between these components may be a key feature
      responsible for the unique pacemaker properties of the SCN observed at a tissue
      and whole animal level.

PMID- 14667144
TI  - Congenic mice reveal sex-specific genetic regulation of femoral structure and
      strength.
AB  - Genetic linkage studies in C3H/HeJ (C3H) and C57BL/6J (B6) mice identified
      several chromosomal locations or quantitative trait loci (QTL) linked to femoral
      volumetric bone mineral density (vBMD). From QTL identified on chromosomes (chr)
      1, 4, 6, 13, and 18, five congenic mouse strains were developed. In each of these
      mice, genomic DNA from the QTL region of the donor C3H strain was transferred
      into the recipient B6 strain. Here we report the effects of donated C3H QTL on
      femoral structure, cortical vBMD and bending strength. Femoral structure was
      quantified by the polar moment of inertia (Ip) at the mid-diaphysis, which
      reflects the bending or torsional rigidity of the femur. Although the C3H
      progenitor mice have a smaller Ip than B6 progenitor mice, the congenic mice
      carrying the C3H segment at Chr 4 had significantly increased Ip in both males
      and females, giving these mice stronger femora. In female mice from the congenic
      Chr 1 strain, Ip was increased whereas male mice from the Chr 1 strain had
      smaller femoral cross-sections and significantly reduced Ip. This sex-specific
      effect on femoral structure was seen to a lesser extent in Chr 18 congenic mice.
      In addition, cortical vBMD was measured using peripheral quantitative computed
      tomography. Cortical vBMD was similar among most congenic strains except in Chr 6
      congenic mice, where cortical vBMD was significantly less in females, but not in
      males. We conclude that (1) chromosomal QTL from C3H mice, which are genetically
      linked to total femoral vBMD, also regulate femoral structure; (2) the QTL on Chr
      4 improves femoral structure and strength; (3) QTL on Chr 1 and 18 impart sex
      specific effects on femoral structure; and (4) the QTL on Chr 6 imparts a sex
      specific effect on cortical vBMD and femoral strength.

PMID- 14667146
TI  - New quantitative trait loci for the genetic variance in circadian period of
      locomotor activity between inbred strains of mice.
AB  - Provisional quantitative trait loci (QTL) for circadian locomotor period and
      wheel-running period have been identified in recombinant inbred (RI) mouse
      strains. To confirm those QTL and identify new ones, the genetic component of
      variance of the circadian period was partitioned among an F2 intercross of RI
      mouse strains (BXD19 and CXB07). First, a genomic survey using 108 SSLP markers
      with an average spacing of 15 cM was carried out in a population of 259 (BXD19 x
      CXB07)F2 animals. The genome-wide survey identified two significant QTL for
      period of locomotor activity measured by infrared photobeam crossings on mouse
      chromosomes 1 (lod score 5.66) and 14 (lod score 4.33). The QTL on distal
      chromosome 1 confirmed a previous report based on congenic B6.D2-Mtv7a/Ty mice.
      Lod scores greater than 2.0 were found on chromosomes 1, 2, 6, 12, 13, and 14. In
      a targeted extension study, additional genotyping was performed on these
      chromosomes in the full sample of 341 F2 progeny. The 6 chromosome-wide surveys
      identified 3 additional QTL on mouse chromosomes 6, 12, and 13. The QTL on
      chromosome 12 overlaps with circadian period QTL identified in several prior
      studies. For wheel-running period, the chromosome-wide surveys identified QTL on
      chromosomes 2 and 13 and one highly suggestive QTL on proximal chromosome 1. The
      results are compared to other published studies of QTL of circadian period.

PMID- 14667147
TI  - Noncircadian regulation and function of clock genes period and timeless in
      oogenesis of Drosophila melanogaster.
AB  - Circadian clock genes are ubiquitously expressed in the nervous system and
      peripheral tissues of complex animals. While clock genes in the brain are
      essential for behavioral rhythms, the physiological roles of these genes in the
      periphery are not well understood. Constitutive expression of the clock gene
      period was reported in the ovaries of Drosophila melanogaster; however, its
      molecular interactions and functional significance remained unknown. This study
      demonstrates that period (per) and timeless (tim) are involved in a novel
      noncircadian function in the ovary. PER and TIM are constantly expressed in the
      follicle cells enveloping young oocytes. Genetic evidence suggests that PER and
      TIM interact in these cells, yet they do not translocate to the nucleus. The
      levels of TIM and PER in the ovary are affected neither by light nor by the lack
      of clock-positive elements Clock (Clk) and cycle (cyc). Taken together, these
      data suggest that per and tim are regulated differently in follicle cells than in
      clock cells. Experimental evidence suggests that a novel fitness-related
      phenotype may be linked to noncircadian expression of clock genes in the ovaries.
      Mated females lacking either per or tim show nearly a 50% decline in progeny, and
      virgin females show a similar decline in the production of mature oocytes.
      Disruption of circadian mechanism by either the depletion of TIM via constant
      light treatment or continuous expression of PER via GAL4/UAS expression system
      has no adverse effect on the production of mature oocytes.

PMID- 14667148
TI  - Photoperiodic regulation of circulating leukocytes in juvenile Siberian hamsters:
      mediation by melatonin and testosterone.
AB  - The reproductive system of Siberian hamsters (Phodopus sungorus) undergoes rapid
      phenotypic responses to changes in day length that occur around the time of
      weaning. The present experiments tested whether the immune system of Siberian
      hamsters is similarly photoperiodic early in life and whether photoperiodic
      changes in melatonin or gonadal hormone secretions mediate any such responses to
      day length. Circulating blood leukocyte concentrations (WBC) were measured in
      juvenile male Siberian hamsters that were gestated in long-days (LD), transferred
      to short-days (SD) on the day of birth, and subsequently either remained in SD or
      were transferred from SD to LD at 18 days of age (day 18). WBC values were
      comparable between LD and SD hamsters on day 18. Between day 18 and day 32, SD
      hamsters exhibited a 3-fold increase in WBC, whereas LD hamsters failed to
      undergo a significant increase in WBC during this interval. WBC of LD hamsters
      was significantly lower than that of SD hamsters on day 25 and on day 32. In LD
      housed males, peripheral injections of melatonin delivered so as to extend the
      nocturnal duration of elevated endogenous melatonin secretion (i.e., provided in
      late afternoon) on days 18-31 increased WBC as measured on day 32. Peripubertal
      (day 17) gonadectomy abolished the immunosuppressive effect of LD exposure on
      WBC, and treatment with silastic implants containing testosterone suppressed WBC
      independent of photoperiod treatment. These data indicate that juvenile Siberian
      hamsters are immunologically responsive to photoperiod and that the leukocyte
      responses to day length are the result of melatonin-mediated effects of
      photoperiod on testicular hormone secretion.

PMID- 14667149
TI  - Circadian rhythms of locomotor activity in solitary and social species of African
      mole-rats (family: Bathyergidae).
AB  - Mole-rats are strictly subterranean and hardly, if ever, come into contact with
      external light. As a result, their classical visual system is severely regressed
      and the circadian system proportionally expanded. The family Bathyergidae
      presents a unique opportunity to study the circadian system in the absence of the
      classical visual system in a range of species. Daily patterns of activity were
      studied in the laboratory under constant temperature but variable lighting
      regimes in individually housed animals from 3 species of mole-rat exhibiting
      markedly different degrees of sociality. All 3 species possessed individuals that
      exhibited endogenous circadian rhythms under constant darkness that entrained to
      a light-dark cycle. In the solitary species, Georychus capensis, 9 animals
      exhibited greater activity during the dark phase of the light cycle, while 2
      individuals expressed more activity in the light phase of the light cycle. In the
      social, Cryptomys hottentotus pretoriae, 5 animals displayed the majority of
      their activity during the dark phase of the light cycle and the remaining 2
      exhibited more activity during the light phase of the light cycle. Finally in the
      eusocial Cryptomys damarensis, 6 animals displayed more activity during the light
      phase of the light cycle, and the other 2 animals displayed more activity during
      the dark phase of the light cycle. Since all three mole-rat species are able to
      entrain their locomotor activity to an external light source, light must reach
      the SCN, suggesting a functional circadian clock. In comparison to the solitary
      species, the 2 social species display a markedly poorer response to light in all
      aspects. Thus, in parallel with the sociality continuum, there exists a continuum
      of sensitivity of the circadian clock to light.

PMID- 14667150
TI  - Different effects of intensity and duration of locomotor activity on circadian
      period.
AB  - An outstanding unresolved issue in chronobiology is how the level of locomotor
      activity influences length of the free-running, endogenous circadian period
      (tau). To address this issue, the authors studied a novel model, 4 replicate
      lines of laboratory house mice (Mus domesticus) that had been selectively bred
      for high wheel-running activity (S) and their 4 unselected control (C) lines.
      Previous work indicates that S mice run approximately twice as many
      revolutions/day and exhibit an altered dopaminergic function as compared with C
      mice. The authors report that S mice have a tau shorter by about 0.5 h as
      compared with C mice. The difference in tau was significant both under constant
      light (control lines: tau = 25.5 h; selected: tau = 24.9 h) and under constant
      dark (control lines: 23.7 h; selected: 23.4 h). Moreover, the difference remained
      statistically significant even when the effects of running speed and time spent
      running were controlled in ANCOVA. Thus, something more fundamental than just
      intensity or duration of wheel-running activity per se must underlie the
      difference in tau between the S and C lines. However, despite significant
      difference in total wheel-running activity between females and males, tau did not
      differ between the sexes. Similarly, among individuals within lines, tau was not
      correlated with wheel-running activity measured as total revolutions per day.
      Instead, tau tended to decrease with average running speed but increase with time
      spent running. Finally, within individuals, an increase in time spent running
      resulted in decreased tau in the next few days, but changes in running speed had
      no statistically significant effect. The distinctions between effects of duration
      versus intensity of an activity, as well as between the among- versus within
      individual correlations, are critical to understanding the relation between
      locomotor activity and pace of the circadian clock.

PMID- 14667151
TI  - Entrainment of 2 subjective nights by daily light:dark:light:dark cycles in 3
      rodent species.
AB  - Recent work with exotic 24-h light:dark:light:dark (LDLD) cycles indicates
      surprising flexibility in the entrainment patterns of Syrian hamsters. Following
      exposure to an LDLD cycle, hamsters may adopt a form of rhythm splitting in which
      markers of subjective night (e.g., activity, melatonin) are expressed in each of
      the twice daily scotophases. This pattern contrasts markedly with that of
      conventionally entrained hamsters in which markers of subjective night are
      expressed once daily in only 1 of the 2 dark periods. The "split" entrainment
      pattern was examined further here in Syrian and Siberian hamsters and in mice
      exposed to LDLD 7:5:7:5, a condition that reliably induces split activity rhythms
      in all 3 species. The phase angle of entrainment and activity duration were
      generally similar comparing the 2 daily activity bouts in each species. The
      stability of this split entrainment state was assessed by deletions of
      photophases on individual days, by exposure to skeleton photoperiods, and by
      transfer to constant darkness. As in Syrian hamsters, the one-time substitution
      of darkness for one 7-h photophase did not grossly alter activity patterns of
      Siberian hamsters but acutely disrupted the split rhythms of mice. Skeleton light
      pulses of progressively shorter duration did not significantly alter split
      entrainment patterns of either Syrian or Siberian hamsters. Both species
      continued to exhibit stable entrainment with activity expressed in alternate
      scotophases of an LD 1:5 cycle presented 4 times daily. In contrast, the split
      activity rhythms of mice were not maintained under skeleton pulses. In constant
      darkness, rhythms of Siberian hamsters remained distinctly split for a minimum of
      2 cycles. Split entrainment to these novel LDLD and 4-pulse skeleton lighting
      regimes demonstrates a marked degree of plasticity common to the circadian
      systems of several rodent species and identifies novel entrainment patterns that
      may be reliably elicited with simple environmental manipulations. Inter- and
      intraspecific differences in the stability of split activity rhythms likely
      reflect differences in coupling interactions between the component circadian
      oscillators, which, adopting separate phase relations to these novel LD cycles,
      yield a split entrainment pattern.

PMID- 14667153
TI  - Dithizone derivatives as sensitive water soluble chromogenic reagents for the ion
      chromatographic determination of inorganic and organo-mercury in aqueous
      matrices.
AB  - Water-soluble sulfonate and the novel carboxylate analogues of dithizone,
      combined with ion interaction chromatography on a Dionex Acclaim 120 C18 silica
      column (250 x 4.6 mm id) with an eluent consisting of 10 mM tetrabutylammonium
      bromide and 60:40 methanol:water, have been developed as highly sensitive
      chromogenic ligands for the quantitative isocratic determination of inorganic and
      organo-mercury compounds in aqueous matrices in under 12 min. Using an optimised
      post column reagent system containing 0.65 mM dye, 0.5% Triton X-100 and 50 mM
      sodium hydroxide, good linearity (0-7.5 mg L(-1) R2 > 0.999), reproducibility
      using peak area measurements (RSD 0.69-1.38%, n = 8), and limits of detection (4
      12 microg L(-1)) were achieved for methyl mercury, inorganic mercury and phenyl
      mercury.

PMID- 14667152
TI  - Combinations of bright light, scheduled dark, sunglasses, and melatonin to
      facilitate circadian entrainment to night shift work.
AB  - Various combinations of interventions were used to phase-delay circadian rhythms
      to correct their misalignment with night work and day sleep. Young participants
      (median age = 22, n = 67) participated in 5 consecutive simulated night shifts
      (2300 to 0700) and then slept at home (0830 to 1530) in darkened bedrooms.
      Participants wore sunglasses with normal or dark lenses (transmission 15% or 2%)
      when outside during the day. Participants took placebo or melatonin (1.8 mg
      sustained release) before daytime sleep. During the night shifts, participants
      were exposed to a moving (delaying) pattern of intermittent bright light
      (approximately 5000 lux, 20 min on, 40 min off, 4-5 light pulses/night) or
      remained in dim light (approximately 150 lux). There were 6 intervention groups
      ranging from the least complex (normal sunglasses) to the most complex (dark
      sunglasses + bright light + melatonin). The dim light melatonin onset (DLMO) was
      assessed before and after the night shifts (baseline and final), and 7 h was
      added to estimate the temperature minimum (Tmin). Participants were categorized
      by their amount of reentrainment based on their final Tmin: not re-entrained
      (Tmin before the daytime dark/sleep period), partially re-entrained (Tmin during
      the first half of dark/sleep), or completely re-entrained (Tmin during the second
      half of dark/ sleep). The sample was split into earlier participants (baseline
      Tmin < or = 0700, sunlight during the commute home fell after the Tmin) and later
      participants (baseline Tmin > 0700). The later participants were completely re
      entrained regardless of intervention group, whereas the degree of re-entrainment
      for the earlier participants depended on the interventions. With bright light
      during the night shift, almost all of the earlier participants achieved complete
      re-entrainment, and the phase delay shift was so large that darker sunglasses and
      melatonin could not increase its magnitude. With only room light during the night
      shift, darker sunglasses helped earlier participants phase-delay more than normal
      sunglasses, but melatonin did not increase the phase delay. The authors recommend
      the combination of intermittent bright light during the night shift, sunglasses
      (as dark as possible) during the commute home, and a regular, early daytime
      dark/sleep period if the goal is complete circadian adaptation to night-shift
      work.

PMID- 14667154
TI  - Analysis of green copper pigments in illuminated manuscripts by micro-Raman
      spectroscopy.
AB  - In the majority of the literature describing green coloured materials used on
      ancient painting layers (15th or 16th century), two copper greens are mainly
      cited: malachite [CuCOr3 x Cu(OH)2] and verdigris [Cu(CH3COO)2 x [Cu(OH)2]3 x
      2H2O]. It is shown, by micro-Raman spectroscopy, that the artists were actually
      employing more than these two copper greens, in particular various copper
      sulfates, among which the most common pigment found is posnjakite [CuSO4 x
      3Cu(OH)2 x H2O]. In contrast to the PIXE (particle induced X-ray emission)
      technique, Raman spectroscopy is a technique of choice, able to distinguish not
      only a copper sulfate from a carbonate or acetate but also the different sulfates
      themselves; in this respect, we found that the high wavenumber region (2800-4000
      cm(-1)), characteristic of H2O vibrations, is of particular interest. It is also
      shown that numerous green areas were created with mixtures of a copper sulfate
      mixed with other pigments, for instance to enhance the colour depth. Finally, in
      some cases, no green pigment is actually employed but the colour is obtained by
      intimately mixing yellow and blue pigments. All these results led to a new look
      at the pigments which were in use on the palettes of the ancient artists.

PMID- 14667155
TI  - FT-Raman spectroscopy of lichens on dolomitic rocks: an assessment of metal
      oxalate formation.
AB  - The FT-Raman spectra of five epilithic lichen taxa growing on dolomite and
      magnesium-rich carbonate rocks have been analysed and interpreted for the key
      molecular marker bands associated with calcium oxalate monohydrate (whewellite),
      calcium oxalate dihydrate (weddelite) and magnesium oxalate dihydrate. From the
      results, it can be concluded that the biomineral product of lichen
      biodeterioration involves the calcareous part of the substratum only; no trace of
      magnesium oxalate has been found in the Raman spectra. Two of the species,
      Lecanora sulfurea and Aspicilia calcarea, produce calcium oxalate monohydrate
      exclusively, but Dirina massiliensis f. sorediata, D. massiliensis f.
      massiliensis and Tephromela atra produce significant quantities of the dihydrate.
      An explanation is advanced for the exclusive accumulation of calcium oxalate into
      the lichen thallus despite the significant presence of magnesium ions.

PMID- 14667156
TI  - The acoustic spectrophonometer: a novel bioanalytical technique based on
      multifrequency acoustic devices.
AB  - A measurement technique similar to optical absorption spectroscopy but based on
      evanescent acoustic waves is described in this paper. This format employs a
      planar spiral coil to vibrate a single crystal of quartz from 6 to 400 MHz, in
      order to measure multifrequency acoustic spectra. Consistency with the defined
      Sauerbrey and Kanazawa terms K1 and K2 when applied to multiple frequencies was
      found for these specific operating conditions in terms of a significant fit
      between the measured and calculated values: For an IgG surface density of 13.5 ng
      mm(-2) the measured value of K1 is 22.5 x 10(-6) and the calculated value is 20.4
      x 10(-6), whilst for glycerol viscous loadings of 5.131 cP the measured value of
      K2 is 0.47 and the calculated value is 0.54. Thus for these specific surface
      loadings the multifrequency data fits to the predictions of the Sauerbrey model
      to within 10% and to Kanazawa model within 13%. However collective frequency
      shifts for 5.131 cP solutions of sucrose, dextran and glucose were found to
      exhibit an unanticipated additional variability (R2 < 0.4) with frequency, but
      retained a square root of frequency dependency within a factor 2 of the
      interpolated K2 values. The response to the 5.131 cP dextran solution was found
      to be significantly below the other isoviscous solutions, with a substantially
      reduced frequency shift and K2 value than would be expected from its bulk
      viscosity. In comparison with these viscous solutions, IgG protein films
      consistently produced linear frequency shifts with little scatter (R2 > 0.96)
      that were proportional to the operating frequency, and fully consistent with the
      Sauerbrey model under these specific conditions. A t-test value of 14.52 was
      calculated from the variance and mean of the two groups, and demonstrates that
      the acoustic spectrophonometer can be used to distinguish between the acoustic
      impedance characteristics of two chemical systems that are not clearly
      differentiable at a single operating frequency.

PMID- 14667157
TI  - Analysis of pesticide residues in lettuce by large volume-difficult matrix
      introduction-gas chromatography-time of flight-mass spectrometry (LV-DMI-GC-TOF
      MS).
AB  - A multi-residue method is described that eliminates the need for a clean-up step
      and thus allows the rapid determination of pesticides in crude extracts of
      lettuce. Samples were extracted with a mixture of ethyl acetate, Na2SO4 and
      NaHCO3 and the crude extracts analysed directly using large volume-difficult
      matrix introduction (LV-DMI) in combination with gas chromatography-time of
      flight-mass spectrometry (GC-TOF-MS). The LV-DMI procedure described was
      evaluated for the analysis of dimethoate, pyrimethanil, chlorothalonil,
      vinclozolin, furalaxyl and oxadixyl. Satisfactory response was obtained at the
      lowest calibrated level (LCL) of 0.0025 microg ml(-1), with good linearity over
      the range 0.0025-0.5 microg ml(-1) (0.005-1.0 mg kg(-1) equivalent). Average
      recoveries between 73 and 118% were obtained at the 0.01-0.5 mg kg(-1) levels
      with RSD values < or = 13%.

PMID- 14667158
TI  - Fast volatile organic compound recovery from soil standards for analysis by
      thermal desorption gas chromatography.
AB  - The development of high-throughput environmental screening assays are needed to
      meet high-specification data quality objectives (DQOs) that require large numbers
      of samples to be taken and analysed rapidly. The acquisition and stabilisation of
      the sample is a key technical and operational challenge in analytical sequences
      associated with the determination of volatile organic compound (VOC)
      contamination of soils. Further the development of miniaturised and embedded
      analytical systems for environmental conditioning monitoring requires the
      development of new sampling techniques. A proof-of-concept study is described
      that shows how pressurised gas, in this case carbon dioxide, may be used to
      recover reversibly-bound VOCs from soil into an adsorbent sampler, and then
      analysed by thermal desorption-gas chromatography. The effects of the volume of
      the pressurised gas, the gas flow rate and the mass of the soil sample on the
      recovery efficiency and breakthrough from the adsorbent trap were investigated in
      a preliminary characterisation study. Two distinct approaches were identified.
      The first involved ventilation of the voids within the soil matrix to displace
      the soil-gas headspace, a rapid screening approach. The second involved a more
      prolonged purge of the matrix to strip reversibly bound species into the gas
      phase and hence pass them into the adsorbent trap, a purge and trap approach. The
      shortest possible sample processing time required to yield analytically useful
      responses was 5 s with the use of the headspace approach. In this case n-octane,
      benzene and toluene were recovered from conditioned spiked soil samples at
      concentrations in the range 42 to 1690 mg kg(-1). The limit of detection for the
      system was estimated to be no greater than 1.2 mg kg(-1). Using the purge and
      trap variant enabled recovery efficiencies greater than 93% to be achieved with
      liquid spikes of n-octane onto soil samples. These preliminary studies showed
      that a system based on this approach would need to balance recovery efficiency,
      time and analyte breakthrough from the adsorbent trap.

PMID- 14667159
TI  - A 50% n-octylmethyl, 50% diphenyl-polysiloxane as stationary phase with unique
      selectivity for gas chromatography.
AB  - An n-octylmethyl, diphenyl-polysiloxane called SOP-50-Octyl was prepared by a
      condensation reaction of bis(dimethylamino) n-octylmethylsilane with
      diphenylsilanediol. The resulting copolymer was a gum with high molecular weight
      and was obtained with a yield of 80%. 1H and 29Si NMR spectroscopy revealed that
      the copolymer was a 52% octylmethyl, 48% diphenyl-polysiloxane with random
      microstructure. Small cyclic impurities could be almost quantitatively removed
      via a purification step. SOP-50-Octyl was used as stationary phase for the
      preparation of wall coated open tubular fused silica capillary columns for gas
      liquid chromatography. The capillary columns exhibited high separation efficiency
      and high inertness. The stationary phase offered a unique selectivity due to its
      unique composition. The Rohrschneider-McReynolds constants indicated a low
      overall polarity in spite of the high phenyl content, as the polarity was
      distinctly decreased by the octyl substituent. Furthermore, the octyl substituent
      was responsible for a high column bleed, reducing the maximum allowable operating
      temperature to 280 degrees C. The elution temperatures of apolar compounds were
      increased due to increased interaction of the octyl substituent with the
      analytes. Some applications with volatile and semi-volatile organic compounds
      illustrate that SOP-50-Octyl is an excellent choice for confirmational analyses.

PMID- 14667160
TI  - Study of continuous two-dimensional thermal field-flow fractionation of polymers.
AB  - Two-dimensional thermal field-flow fractionation (2D-ThFFF) is a new instrumental
      technique devised for continuous fractionation of soluble macromolecules and
      particles. The sample mixture is introduced into a disc-shaped channel and the
      separated sample components are collected continuously from the channel outlets.
      The method is based on a two-dimensional fractionation mechanism with radial and
      tangential flow components in the channel. The effects of flow components and
      thermal gradient on the fractionation were studied in the separation of
      polystyrene samples of different molecular masses using cyclohexane or a binary
      solvent consisting of 25% ethylbenzene and 75% cyclohexane as carrier. The
      continuous separation of polystyrene samples was improved with increasing thermal
      gradient and with the use of slow radial and tangential flow rates. The technique
      can be applied to preparative continuous separation of macromolecules.

PMID- 14667161
TI  - Capillary electrochromatography with monolithic-silica columns. II. Preparation
      of amphiphilic silica monoliths having surface-bound cationic octadecyl moieties
      and their chromatographic characterization and application to the separation of
      proteins and other neutral and charged species.
AB  - Three different synthetic routes have been introduced and evaluated for the
      preparation of amphiphilic silica-based monoliths possessing surface-bound
      octadecyl ligands and positively charged groups. The amphiphilic silica monoliths
      (designated as cationic C18-monoliths) have been designed for use in reversed
      phase capillary electrochromatography (RP-CEC) with hydro-organic mobile phases.
      These amphiphilic stationary phases yielded anodic electroosmotic flow (EOF) over
      a wide range of mobile phase pH. The magnitude of EOF remained constant up to pH
      4.0 and then decreased at pH > 4.0 due to the ionization of silanol groups and
      the subsequent decrease in the net positive surface charge density of the
      amphiphilic monoliths. The cationic C18-monoliths exhibited reversed-phase
      chromatography (RPC) behavior toward non-polar solutes (e.g., alkyl benzenes),
      which parallels that observed with octadecyl-silica (ODS) monoliths. On the other
      hand, the amphiphilic stationary phases exhibited both non-polar and polar
      interactions toward slightly polar solutes such as anilines and PTH-amino acids.
      CEC retention factor k* and velocity factor k*e, which reflects the contribution
      of the electrophoretic mobility, were evaluated for charged solutes such as
      anilines and proteins.

PMID- 14667162
TI  - Solvent and pH effects on fast and ultrasensitive 1,1'-oxalyldi(4
      methyl)imidazole chemiluminescence.
AB  - Solvent and pH effects on fast and ultrasensitive 1,1'-oxalyldi(4
      methyl)imidazole chemiluminescence (OD4MI-CL) were studied. The influences of
      these two factors on the complex OD4MI-CL reaction are discussed within a
      conceptual prototype for developing aqueous and non-aqueous capillary
      electrophoresis (ACE and NACE) devices with OD4MI-CL detection. The reaction
      channel length and OD4MI yield from the reaction between bis(2,4,6
      trichlorophenyl) oxalate (TCPO) and 4-methylimidazole in the channel will be
      influenced by pH, water volume fraction, and cosolvent properties of the
      solution. Optimum OD4MI-CL efficiency is observed at pH 6.5 when 1-propanol,
      which has a low dielectric constant (epsilon = 20.8), is used as the NACE solvent
      in the separation channel. Water (epsilon = 80.1), the solvent in the ACE
      separation channel, acts similarly to a high dielectric constant organic solvent
      in NACE because the disadvantages normally associated with TCPO-CL reactions in
      water disappear due to the faster OD4MI-CL reaction versus OD4MI decomposition in
      aqueous solution. Therefore, it is expected that the OD4MI-CL detection system
      can be used in both NACE and ACE devices without requiring detector
      modifications. We also conclude that OD4MI-CL detection in NACE and ACE devices
      will be much more sensitive than the TCPO-CL detection used in current NACE
      devices.

PMID- 14667163
TI  - Liquid polymer nano-PEBBLEs for Cl- analysis and biological applications.
AB  - The first nanometer scale anion sensing fluorescent spherical nanosensors, or
      PEBBLEs (probes encapsulated by biologically localized embedding) have been
      developed for the intracellular monitoring of chloride. The general scheme for
      the polymerization and introduction of sensing components creates a matrix that
      allows for the utilization of the highly selective ionophores used in poly(vinyl
      chloride) and poly(decyl methacrylate) ion-selective electrodes. We have
      demonstrated that our previously developed scheme for cation sensors can be
      utilized to tailoring selective submicron sensors for use in intracellular
      measurements of biologically relevant anions for which selective enough
      fluorescent probes do not exist. Three schemes were attempted for the development
      of chloride sensitive PEBBLEs. The first two used the Chloride ionophore
      indium(III) octaethylporphyrin chloride (In(OEP)Cl) (1) as an ionophore working
      in tandem with a chromoionophore and (2) as a chromoionophore with a peak shift
      generated by chloride mediated breaking of hydroxide ion-bridged porphyrin dimer.
      The third method used the optically silent Chloride ionophore III (ETH 9033)
      working in tandem with chromoionophore III (ETH 5350) to indirectly monitor Cl-
      activity by reporting the H+ coextracted into the matrix. Method 3 gave the most
      promising results, at a pH of 7.2 these PEBBLEs have a limit of detection of 0.2
      mM Cl- with a linear dynamic range of 0.4 mM-190 mM Cl-. These PEBBLEs were
      delivered into C6 glioma cells, utilizing a gene gun, and intracellular chloride
      levels were monitored during ion-channel stimulation by kainic acid.

PMID- 14667164
TI  - Electrochemical biosensors utilising electron transfer in heme proteins
      immobilised on Fe3O4 nanoparticles.
AB  - Fe3O4 nanoparticles cast on pyrolytic graphite (PG) electrodes were used to
      immobilize hemoglobin (Hb), myoglobin (Mb) and horseradish peroxidase (HRP). The
      Fe3O4 nanoparticles provided a favorable microenvironment for the proteins to
      directly transfer electrons with electrodes. The protein-Fe3O4 films were used to
      electrochemically catalyze the reduction of oxygen, trichloroacetic acid, nitrite
      and hydrogen peroxide, and showed a potential applicability in fabricating
      biosensors. Transmission electron microscopy (TEM), UV-visible absorption and
      reflectance absorption infrared (RAIR) spectroscopy, and cyclic and square wave
      voltammetry, were used to characterize the films.

PMID- 14667165
TI  - Rapid polyelectrolyte-based immunofiltration technique for testosterone detection
      in serum samples.
AB  - A new immunofiltration assay for testosterone is proposed. During the first step
      of the assay, testosterone molecules in serum samples compete in solution with
      the testosterone-peroxidase conjugate for interaction with anti-testosterone
      antibodies pre-bound to the conjugate between staphylococcal protein A and
      polymethacrylate polyanion. The reaction mixture is then filtered through a
      membrane charged with immobilized poly(N-ethyl-4-vinylpyridinium) polycation. The
      filtration is accompanied by a rapid separation of the polyanion containing
      complexes due to high-affinity electrostatic interactions. Following removal of
      unbound compounds the immobilized peroxidase is detected using a substrate that
      produces an insoluble coloured product. The proposed assay has been shown to
      combine high speed (20 min) and sensitivity (0.1 ng ml(-1)), and to be applicable
      for out-of-laboratory conditions. Based on densitometric measurements, the RSD of
      the assay is calculated to be 3.2-5.1% (n = 4). The proposed assay is 4 times
      faster than the microplate enzyme immunoassay (ELISA) based on the same
      immunoreagents. Pre-incubation of the antibody and the polyanion-protein A
      conjugate at a certain ratio excludes the influence of immunoglobulins from the
      tested serum samples on the assay results. The polyanion-protein A conjugate can
      be used as a universal reagent, eliminating the necessity to modify specific
      antibodies for each immunoassay.

PMID- 14667166
TI  - Determination of trace concentrations of dissolved nitric oxide in a biological
      buffer.
AB  - A new real-time method for measuring a trace concentration of nitric oxide (NO)
      in a complex matrix routinely used in pharmacological studies of its bioactivity
      is described. NO was quantified as a gas by chemiluminescence after extraction
      from a continuous liquid sample flow with a limit of detection of 0.042 nmol dm(
      3) at a signal to noise ratio of 3. Theories to calculate the concentration of NO
      in the liquid sample flow from a direct measurement of NO in the extraction
      carrier gas are presented. The efficiency of extraction is determined by a
      stopflow experiment. An example is presented of the measurement of the steady
      state concentrations of NO in Krebs-bicarbonate buffer at pH 7.4 and 37 degrees C
      when its liquid surface is sequentially exposed to gases containing various
      concentrations of NO in O2 plus CO2.

PMID- 14667167
TI  - Gas phase electrochemical detection of single latex particles.
AB  - In this study we describe zero current potentiometric measurements in a gaseous
      flame electrolyte, for the detection of single latex particles. Combustion of
      polystyrene latex particles when added to a premixed hydrogen/oxygen/nitrogen
      flame, results in an increase in charged species relative to the surrounding
      hydrogen flame. As a consequence of this increase in ionic concentration over
      background, short-lived potential difference transients were measured between two
      platinum indicator electrodes placed in a two-compartment flame electrochemical
      cell (described in Electrochem. Commun., 2001, 3, 675-681). The frequency of the
      transient events was dependent on the number density of latex particles in
      solution. It is proposed that each short-lived transient event corresponds to the
      combustion of single latex particles in a flame. A potential difference maximum
      of 0.56 V when 3.0 microm diameter particles were added to the flame was
      measured. Also it was shown that it is possible to detect 0.3 microm diameter
      latex particles using the same technique. It is postulated that the physical
      basis of the potential difference is due to the establishment of
      diffusion/junction potential due to the increase in ionisation from polystyrene
      combustion at the surface of one indicator electrode. This methodology may be
      applied to the detection of particulates composed of ionisable species (organic
      or inorganic) in gaseous environment such as bacteria, viruses, pollen grains and
      dust.

PMID- 14667168
TI  - A novel flow-through microdialysis separation unit with integrated differential
      potentiometric detection for the determination of chloride in soil samples.
AB  - In this paper, a novel and miniaturised flow-through dialysis-based
      potentiometric detector is proposed for the determination of chloride in soil
      samples. The outstanding feature of the designed unit is the integration of
      analyte isolation from matrix constituents via membrane separation with
      differential potentiometric detection. Two identical tubular all-solid-state
      Ag/AgCl ion selective electrodes (ISEs) were assembled respectively at the inlet
      and outlet of the acceptor channel. Thus, as a consequence of the continuous
      forward flow of solutions through the microdialyser the outlet tube becomes the
      indicator electrode for the analyte diffusate while the nested tube at the
      entrance serves as reference electrode. The effect of physical and chemical
      parameters on the mass transfer efficiency is discussed in detail and compared
      with conventional configurations involving downstream detection. The membrane
      morphology for optimum dialysis performance is also thoroughly evaluated in terms
      of thickness, porosity and molecular weight cut-off. Higher dialysis efficiency
      and reduction of dilution factors up to a value of 5 were attained by halting the
      recipient stream temporarily. Under the optimised conditions, a dynamic working
      range of 5-5000 mg l(-1) chloride with a linear interval between 10 and 5000 mg
      l(-1) (for 1 min stopped-flow and 200 microl sample volume), a repeatability
      better than 3.0% and a 3 sigma(blank) detection limit of 1.2 mg l(-1) chloride
      were the analytical figures of merit of the devised configuration. The
      potentiometric dialysis sensor features extreme tolerance to high molecular
      weight interfering matrix compounds (> 1000 mg l(-1) humic acid), which makes it
      specially suited for the interference-free potentiometric determination of
      chloride in soils containing high levels of organic matter. The miniature size,
      low-reagent consumption and high analytical throughput (25-40 h(-1)) also warrant
      its applicability to in-field monitoring or screening schemes. The accuracy of
      the measurements was assessed using ion-chromatography as an external reference
      method. A mean t-test showed no statistical differences between both
      methodologies at the 95% confidence level.

PMID- 14667169
TI  - Pollution toxicity to the transmission of larval digeneans through their
      molluscan hosts.
AB  - The increased occurrence of pollutants in ecosystems is a continuing area of
      concern. It is known that numerous diseases of wild aquatic animals can occur
      with decreased or increased prevalences in areas associated with high or chronic
      levels of pollution. This may have serious implications for environmental health.
      There has consequently been an increasing number of laboratory and field studies
      on disease transmission under polluted conditions, especially focusing on
      digeneans of medical or economic importance. The effect of pollutants to the
      transmission of larval digeneans (miracidia, cercariae, metacercariae) and snail
      digenean interactions is therefore considered. An overview and interpretation of
      the published literature on laboratory and field studies is provided. It is
      apparent from these studies that the influence of pollutants on digenean
      transmission is highly complex with much of the observed effects in the
      laboratory often masked by a complexity of other factors in the field. Future
      studies would benefit from a standardisation of experimental procedures,
      increasing the number of combined laboratory and field studies, and increasing
      the complexity of the experiments undertaken.

PMID- 14667170
TI  - Marine parasites as pollution indicators: an update.
AB  - Eight major reviews are cited to indicate a recent knowledge explosion on the use
      of marine parasites as potential indicators of pollution. A literature update is
      given for the period 1995-2001. An analysis of the publications cited is used to
      provide 10 refined criteria for selecting parasites as indicator/monitor species.
      Previously unpublished data on Diclidophora merlangi and Dictyocotyle coeliaca
      confirm their value as potential indicators of hydrocarbon pollution in the North
      Sea. An extensive knowledge of D. merlangi is summarised to emphasize its
      potential value as an indicator species and also to encourage studies on the
      health status and immune responses of its host when subjected to pollutant
      stressors and infection with this monogenean. A discussion focuses on
      publications which have reported significant recent advances in this area of
      research and also on accompanying issues, problems and controversies. These
      selected publications are used to suggest species, stages in the development of
      species and assemblages of species worthy of further more detailed investigations
      into their value as indicators/monitors of pollution. It is predicted that
      further good progress will be made when contaminants can be accurately
      identified, their precise effects on both host and parasite can be measured by
      histochemical and biological methods and the roles of contaminants and parasites
      in causing disease can be assessed separately. About 100 references are cited.

PMID- 14667171
TI  - Parasite communities as indicators of recovery from pollution: parasites of roach
      (Rutilus rutilus) and perch (Perca fuviatilis) in central Finland.
AB  - We compared parasite communities in fish taken from a polluted lake (L. Vatia)
      and two control lakes before (1986) and after (1995) nine years of markedly
      reduced chemical and nutrient loading from a pulpmill in central Finland.
      Discriminant analyses of the 1995 data, using a function based on the 1986 data,
      showed that the parasite communities in the fish from the two control lakes had
      changed relatively little, whereas those from L. Vatia had converged on those
      from the mesotrophic control lake, indicating substantial recovery from the
      effects of pollution. Only a few species of parasites provided evidence for
      recovery. These were anodontid glochidia, which had increased markedly in perch,
      Rhipidocotyle fennica in roach and R. campanula in both fish species. This
      suggests that the recovery of the polluted lake involved increased populations of
      anadontid clams in shallow waters. On the other side decrease of Dermocystidium
      percae on perch fins and Ichthyophthirius multifiliis on roach indicate increased
      immune responses in the fish, reflecting better water quality. Other parts of the
      system have apparently not yet recovered.

PMID- 14667172
TI  - Accumulation of heavy metals by intestinal helminths in fish: an overview and
      perspective.
AB  - Intestinal helminths of fish are of increasing interest as potential
      bioindicators for heavy metal contamination in aquatic habitats. Among these
      parasites cestodes and acanthocephalans in particular have an enormous heavy
      metal accumulation capacity exceeding that of established free living sentinels.
      Metal concentrations several thousand times higher in acanthocephalans than in
      host tissues were described from field and laboratory studies. Whereas larval
      stages inside their intermediate hosts are not able to take up high quantities of
      metals, young worms begin to take up metals immediately after infection of the
      final host. After four to five weeks of exposure, the parasites reach a steady
      state concentration orders of magnitude higher than the ambient water level.
      Thus, acanthocephalans are not only very effective in taking up metals, but they
      can also respond very rapidly to changes in environmental exposure. The mechanism
      which enable acanthocephalans to take up metals from the intestinal lumen of the
      host appears to be based on the presence of bile acids, which form organo
      metallic complexes that are easily absorbed by the worms due to their
      lipophilicity. Investigations of the environmental conditions affecting metal
      uptake have shown that the parasites are more consistent and reliable indicators
      for metal pollution than the host tissues as metal levels of the latter are much
      more dependent on the water chemistry. Thus, after some years of research on the
      uptake of metals by acanthocephalans and on the factors affecting metal
      accumulation in intestinal parasites it should be asked if acanthocephalans meet
      the criteria commonly accepted for sentinels. If parasites can be considered as
      promising sentinels, we need reasons for the establishment of 'new' indicators.
      Therefore, this review summarises the present knowledge about parasites as
      bioindicators and compares the accumulation properties of parasites and
      established free living indicators. Finally, this review presents possible
      answers to the question why it could be advantageous to have new and even more
      sensitive indicators for environmental monitoring purposes.

PMID- 14667173
TI  - Fish macroparasites as indicators of heavy metal pollution in river sites in
      Austria.
AB  - This paper describes two approaches to evaluate the use of fish macroparasites as
      bioindicators of heavy metal pollution at selected river stretches in Austria.
      Firstly changes in the diversity and richness of endoparasites of the cyprinid
      barbel, Barbrus barbuls (L.), were tested in relation to heavy metal contents in
      the aquatic system. Secondly, the bioaccumulation potential of cadmium, lead and
      zinc was assessed in the acanthocephalan, Pomphorhynchus laevis (Miller, 1776),
      and compared with that in the muscle, liver and intestine of its barbel host. The
      present results indicated that in order to validate the role of parasite
      community patterns related to heavy metal pollution, more investigations on food
      web dynamics, interelationships between parasites and the presence/absence of
      intermediate hosts will be essential. Heavy metal concentrations differed
      significantly between the organs of barbel and P. laevis (P=0.001) with levels up
      to 2860 fold in the parasite. The high level of heavy metal accumulation in P.
      laevis compared with that in its barbel host, suggests that despite variability
      in the parasite infrapopulation, host mobility and feeding behaviour, P. laevis
      is a most sensitive indicator of heavy metals in aquatic ecosystems.

PMID- 14667174
TI  - Inflammatory interactions in fish exposed to pollutants and parasites: a role for
      apoptosis and C reactive protein.
AB  - Although previous studies have highlighted the inflammatory responses of fish
      infected with parasites and exposed to pollutants, very little is known about how
      these two stressors interact within the fish. In this review, which also contains
      original data, the effect of these two parameters on the fish inflammatory
      response is assessed and, in particular, the role of apoptosis and the acute
      phase protein, C reactive protein, is evaluated. In Cyprinus carpio exposed to
      0.5 mg NH4+ l(-1) or 0.1 mg Cd2+ l(-1) and experimentally infected with the blood
      fluke, Sanguinicola inermis, the pollutant type and the order in which the fish
      experiences the parasite and toxicant, significantly affects the ultrastructural
      appearance and cellular content of the pronephros and thymus. This is reflected
      in the intensity of infection where the pollutant appears to have less effect on
      an established infection. Both stressors, pollutant and infection, may mediate
      their effects via the endocrine system. Studies have revealed that cortisol at
      100 ng ml(-1) is able to induce apoptosis in pronephric cells of carp and that an
      increase in apoptosis is associated with an increase in phagocytosis in this
      immune organ. In addition, C reactive protein, which is used as a biomarker of
      the inflammatory response in humans and other mammals, is evaluated as a possible
      indicator of physiological states in fish exposed to pathogens and pollutants.

PMID- 14667175
TI  - Cadmium effects on Ichthyophthirius: evidence for metal-sequestration in fish
      tissues following administration of recombinant vaccines.
AB  - We are developing Tetrahymena thermophila as a delivery system for recombinant
      vaccines against parasitic protozoa, including the common fish parasite,
      Ichthyophthirius multifiliis. T. thermophila cell lines expressing I. multifiliis
      genes under the control of a cadmium-inducible metallothionein gene promoter
      conferred strong protection against a lethal parasite challenge when administered
      parenterally to naive fish. Nevertheless, given that heavy metals can be toxic to
      parasites, a question arose as to whether protection resulted from Cd residues
      carried over with the vaccine, rather than acquired immunity per se. To address
      this issue, we examined the sensitivity of I. multifiliis to Cd in vitro and
      determined Cd concentrations in different host tissues following i.p. injection
      of juvenile channel catfish with the recombinant vaccine. We found that CdCl2 at
      concentrations > or = 50 ppb were lethal to I. multifiliis theronts in vitro.
      Furthermore, Cd concentrations were clearly elevated in fish tissues and reached
      levels equivalent to 74 ng/g wet weight (74 ppb) in the skin within 14 days of
      injection with recombinant T. thermophila. Nevertheless, fish injected with non
      transformed Tetrahymena grown in the presence or absence of CdCl2 showed no
      significant difference in either relative survival or parasite load following
      direct challenge with I. multifiliis.

PMID- 14667176
TI  - The expression of immune-regulatory genes in rainbow trout, Oncorhynchus mykiss,
      during a natural outbreak of proliferative kidney disease (PKD).
AB  - Proliferative kidney disease (PKD) is a parasitic infection of salmonid fish
      characterized by an apparently abnormal immune response to the presence of the
      myxozoan parasite, Tetracapsuloides bryosalmonae. In order to examine the nature
      of the immune response at the molecular level, the expression of a range of
      immune regulatory genes, including cytokines and cyclooxygenase (COX)-2 was
      examined in naive unexposed fish and in naive fish exposed to parasite-infected
      water at three points during the course of a natural outbreak of PKD. Since fish
      with advanced PKD pathology generally exhibit increased susceptibility to
      secondary infections which is typical of stress/cortisol-mediated immune
      suppression, a further aim of this work was to examine in vitro the influence of
      the glucocorticoid cortisol on the bacterial lipopolysaccharide (LPS)-induced
      expression of the trout cytokine genes studied. Two weeks after the initial
      sampling, naive exposed fish showed a specific profile of up-regulated tumor
      necrosis factor (TNF)-alpha2, COX-2 and, to a lesser extent, transforming growth
      factor (TGF)-beta1 expression. As the disease pathology increased, TNF-alpha2 and
      COX-2 expression returned to normal levels. Stress levels of cortisol suppressed
      the LPS inducibility of pro-inflammatory cytokine genes, although TGF-beta1 and
      TNF-alpha2 appeared to be refractory. These data demonstrate that specific immune
      responses at the molecular level are affected during PKD infection, with the
      cortisol suppression of cytokine expression in vitro providing a possible link to
      PKD-mediated cytokine down-regulation and immune suppression.

PMID- 14667177
TI  - Endocrine disruption, parasites and pollutants in wild freshwater fish.
AB  - Disruption of the endocrine system has been shown to occur in wild freshwater
      fish populations across the globe. Effects range from subtle changes in the
      physiology and sexual behaviour of fish to permanently altered sexual
      differentiation, impairment of gonad development and/or altered fertility. A wide
      variety of adverse environmental conditions may induce endocrine disruption,
      including sub-optimal temperatures, restricted food supply, low pH, environmental
      pollutants, and/or parasites. Furthermore, it is conceivable that any/all of
      these factors could act simultaneously to cause a range of disparate or inter
      related effects. Some of the strongest evidence for a link between an adverse
      health effect, as a consequence of endocrine disruption, and a causative agent(s)
      is between the condition of intersex in wild roach (Rutlius rutilus) in UK rivers
      and exposure to effluents from sewage treatment works. The evidence to indicate
      that intersex in roach (and other cyprinid fish living in these rivers) is caused
      by chemicals that mimic and/or disrupt hormone function/balance in treated sewage
      effluent is substantial. There are a few parasites that affect the endocrine
      system directly in fish, including the tape worm Ligula intestinalis and a few
      parasites from the micropsora phylum. L. intestinalis acts at the level of the
      hypothalamus restricting GnRH secretion (resulting in poorly developed gonads)
      and is one of the very few examples where an endocrine disrupting event has been
      shown to result in a population-level effect (reducing it). It is well
      established that many parasites affect the immune system and thus the most common
      effect of parasites on the endocrine system in fish is likely to be an indirect
      one.

PMID- 14667178
TI  - Lipase inhibition attenuates the acute inhibitory effects of oral fat on food
      intake in healthy subjects.
AB  - The lipase inhibitor, orlistat, is used in the treatment of obesity and reduces
      fat absorption by about 30%. However, the mean weight loss induced by orlistat is
      less than expected for the degree of fat malabsorption. It was hypothesised that
      lipase inhibition with orlistat attenuates the suppressive effects of oral fat on
      subsequent energy intake in normal-weight subjects. Fourteen healthy, lean
      subjects (nine males, five females; aged 25 +/- 1.3 years) were studied twice, in
      a double-blind fashion. The subjects received a high-fat yoghurt 'preload' (males
      400 g (2562 kJ); females 300 g (1923 kJ)), containing orlistat (120 mg) on one
      study day (and no orlistat on the other 'control' day), 30 min before ad libitum
      access to food and drinks; energy intake was assessed during the following 8 h.
      Blood samples were taken at regular intervals for the measurement of plasma
      cholecystokinin (CCK). Each subject performed a 3 d faecal fat collection
      following each study. Energy intake during the day was greater following orlistat
      (10,220 (SEM 928) kJ) v. control (9405 (SEM 824) kJ) (P=0.02). On both days
      plasma CCK increased (P<0.05) after the preload. Plasma CCK 20 min following
      ingestion of the preload was less after orlistat (4.1 (SEM 0.9) pmol/l) v.
      control (5.3 (SEM 0.9) pmol/l (P=0.028); however there was no difference in the
      area under the curve 0-510 min between the two study days. Fat excretion was
      greater following orlistat (1017 (SEM 168) kJ) v. control (484 (SEM 90) kJ)
      (P=0.004). In conclusion, in healthy, lean subjects the acute inhibitory effect
      of fat on subsequent energy intake is attenuated by orlistat and the increase in
      energy intake approximates the energy lost due to fat malabsorption.

PMID- 14667179
TI  - Postprandial carbohydrate metabolism in healthy subjects and those with type 2
      diabetes fed starches with slow and rapid hydrolysis rates determined in vitro.
AB  - The objective of the present study was to investigate the effects of starches
      with differing rates of hydrolysis on exposure to pancreatin in vitro on
      postprandial carbohydrate metabolism in healthy subjects and in subjects with
      type 2 diabetes. Two test starches, prepared from uncooked native granular starch
      products, and naturally enriched with 13C, were consumed in a randomized
      crossover design by eight healthy and thirteen type 2 diabetic subjects. One
      starch was characterized in vitro as being rapidly hydrolysed (R, 94% after 180
      min), and the other was more slowly hydrolysed (S, 51% after 180 min). Each
      subject consumed 50 g of each test starch. In addition, the type 2 diabetic
      subjects consumed 89.7 g of the S starch on a separate occasion. Blood samples
      were taken at 10 min intervals for 3 h, and at 20 min intervals for a further 3 h
      during a 6 h postprandial period. Breath 13CO2 enrichment was measured at the
      same time points, and indirect calorimetry was performed for seven 20 min
      sessions immediately before and during the 6 h postprandial period. With the R
      starch, plasma glucose concentrations and serum insulin concentrations rose
      faster and the maximum glucose change was approximately 1.8 times that for the S
      starch, averaged across both subject groups. The areas under the curves for
      glucose and insulin were, respectively, 1.7 and 1.8 times higher for the R starch
      compared with the S starch, averaged across both subject groups. The rate of
      13CO2 output and the proportion of 13C recovered in breath after consumption of
      the R starch was similar for both subject groups. The results provide evidence
      that starches which have different rates of hydrolysis in vitro result in
      different patterns of glycaemia and insulinaemia in both healthy adults and in
      diet-controlled type 2 diabetic subjects. Data from the hydrolysis of novel
      starch products in vitro, therefore, are useful in predicting glycaemic responses
      in vivo.

PMID- 14667180
TI  - The optimum dietary indispensable amino acid pattern for growing Atlantic salmon
      (Salmo salar L.) fry.
AB  - To determine the optimum indispensable (I) amino acid (AA) balance in Atlantic
      salmon (Salmo salar L.) fry, a single protocol established for the pig was
      adapted. The balance was calculated from the reduction in N gain after replacing
      about 45% of a single IAA by a mixture of dispensable AA in isonitrogenous diets.
      We confirmed that the mixture of AA simulating the AA pattern of cod-meal protein
      and gelatine (46:3, w/w) was used with the same efficiency as cod-meal protein
      and gelatine. From the deletion experiment an optimum balance between the IAA was
      derived. Expressed relative to lysine = 100, the optimal balance was: arginine 76
      (SE 0.2), histidine 28 (SE 2.2), methionine + cystine 64 (SE 1.7), phenylalanine
      + tyrosine 105 (SE 1.6), threonine 51 (SE 2.4), tryptophan 14 (SE 0.7), valine 59
      (SE 1.7). No estimates were made for isoleucine and leucine. Expressed as g/16 g
      N, the optimal balance was: arginine 4.0 (SE 0.0), histidine 1.5 (SE 0.1), lysine
      5.3 (SE 0.2), methionine + cystine 3.4 (SE 0.1), phenylaline + tyrosine 5.6 (SE
      0.1), threonine 2.7 (SE 0.1), tryptophan 0.7 (SE 0.0), valine 3.1 (SE 0.1). This
      AA composition is close to that of the Atlantic salmon whole-body, but using it
      as an estimation of the IAA requirements may lead to an overestimation of the
      branched-chain AA requirements and an underestimation of aromatic and S
      containing AA requirements. The results are discussed in accordance with the key
      assumptions associated with the model used (broken-line model, IAA efficiencies
      and maintenance requirements).

PMID- 14667181
TI  - Conjugated linoleic acid (CLA)-enriched milk fat inhibits growth and modulates
      CLA-responsive biomarkers in MCF-7 and SW480 human cancer cell lines.
AB  - Milk enriched in conjugated linoleic acid (CLA) was obtained from cows on pasture
      supplemented with full-fat rapeseeds (FFR; 2.26 g cis 9, trans 11 (c9,t11)
      CLA/100 g fatty acid methyl esters) and full-fat soyabeans (1.83 g c9,t11-CLA100
      g fatty acid methyl esters). A control milk fat (1.69 g c9,t11-CLA/100 g fatty
      acid methyl esters) was obtained from cows fed on pasture only. The present study
      assessed the potency of the CLA-enriched milk fats to modulate biomarkers that
      had previously been observed to respond to c9,t11-CLA in the MCF-7 and SW480 cell
      lines. Cell numbers decreased (P<0.05) by up to 61 and 58% following the
      incubation of MCF-7 and SW480 cells, respectively, for 4 d with milk fats
      (yielding CLA concentrations between 60.2 and 80.6 microM). The FFR milk fat,
      containing the highest CLA content, increased (P<0.05) [14C]arachidonic acid (AA)
      uptake into the monoacylglycerol fraction of MCF-7 and SW480 cells while it
      decreased (P<0.05) uptake into the phospholipid fraction of the latter. This milk
      fat also decreased (P<0.05) [14C]AA conversion to prostaglandin (PG) E2 while
      increasing conversion to PGF2alpha in both cell lines. All milk-fat samples
      increased (P<0.05) lipid peroxidation as measured by 8-epi-PGF2alpha in both cell
      lines. In SW480 cells the milk-fat samples decreased (P<0.05) bcl-2 and cytosolic
      glutathione levels while increasing (P<0.05) membrane-associated annexin V
      levels. All milk-fat samples decreased (P<0.05) the expression of ras in SW480
      cells. These data suggest that milk-fat CLA was effective at modulating synthetic
      CLA-responsive biomarkers.

PMID- 14667182
TI  - Hepatic fatty acid metabolism in rats fed diets with different contents of C18:0,
      C18:1 cis and C18:1 trans isomers.
AB  - In the present study the effects of some C18 fatty acids on hepatic fatty acid
      metabolism have been compared. Male rats were fed cholesterol-free diets
      containing either C18:0, C18:1 cis or C18:1 trans isomers as the variables. In
      accordance with previous work, oleic acid in the diet caused an increase in
      cholesterol concentration in the liver and in the lipoprotein fraction of density
      (d; kg/l) < 1.006. Oleic acid also reduced the triacylglycerol:cholesterol value
      in this fraction. Surprisingly, the C18:1 trans isomers diet induced a decrease
      in the amount of cholesterol in total plasma as well as in the 1.019 < d < 1.063
      lipoprotein fraction. Both oleic acid and C18:1 trans isomers increased the
      concentration of triacylglycerols in the liver. The two C18:1 fatty acids
      differently influenced the hepatic activities of carnitine palmitoyltransferase-I
      and 3-hydroxy-acyl-CoA dehydrogenase; both enzymes were inhibited by C18:1 trans
      isomers, while no change was induced by oleic acid. The activity of the citrate
      carrier was lower in the oleic acid- and C18:1 trans isomers-fed rats, when
      compared with the rats fed stearic acid. No diet effects were seen for the
      activities of acetyl-CoA carboxylase, fatty acid synthase, diacylglycerol
      acyltransferase, citrate synthase and phosphofructokinase. The results are
      interpreted in that oleic acid raised liver triacylglycerol by reducing the
      secretion of it with the d < 1.006 lipoprotein fraction whereas the C18:1 trans
      isomers enhanced liver triacylglycerol by lowering the hepatic oxidation of fatty
      acids.

PMID- 14667183
TI  - Steroids in the intestinal tract of rats are affected by dietary-fibre-rich
      barley-based diets.
AB  - The aim of the present study was to investigate the influence of dietary-fibre
      (DF)-rich barley-based diets on bile acids (BA) and neutral sterols (NS) in the
      intestinal tract of rats. For this purpose, young male Wistar rats (n 50; ten per
      group) weighing about 67 g were fed either a barley-free diet (control group) or
      diets containing 500 g barley meal extrudates/kg or a barley meal-Novelose
      mixture (groups A-D) for 6 weeks. These barley products contained 7-24 g
      resistant starch/100 g and 7-12 g (1 --> 3),(1 --> 4)-beta-glucan/100 g. More
      steroids were transported towards the lower parts of the intestinal tract when
      higher concentrations of macromolecular DF were present in the diets (P < 0.001).
      Tauroconjugated and primary BA dominated in the contents of the small intestine.
      Intense enzymic conversion of BA occurred in the caecum and colon. The
      fermentation of DF affected indirectly the amount of formed secondary BA. The
      main BA present in the caecal contents were muricholic acids, hyodeoxycholic acid
      and cholic acid. The BA spectrum in the colonic contents was different from that
      in the caecum. A higher concentration of NS appeared in the intestinal contents
      of the groups fed the barley-based diets than in the controls (P < 0.005). The
      microbial conversion of cholesterol to coprostanol, cholestanone and coprostanone
      was influenced by the amount and composition of the DF in the gut. DF in the diet
      may affect the concentration and spectrum of steroids in the intestinal tract.
      The results are relevant for the discussion of mechanisms behind the cholesterol
      lowering effects of DF.

PMID- 14667184
TI  - Villus height and gut development in weaned piglets receiving diets containing
      either glucose, lactose or starch.
AB  - The present study was designed to evaluate the differential effects of dietary
      glucose, lactose and starch on small-intestinal morphology, organ weights. pH of
      chyme and haptoglobin levels in blood plasma of weaned piglets. It was
      hypothesised that lactose consumption would ameliorate the weaning-induced
      decrease in gut integrity. A total of forty-two barrows were used. Piglets were
      weaned at 27 (SD 0.8) d of age and weighed 8.0 (SD 0.51) kg. On the day before
      weaning (day -1) all pigs were blocked according to body weight and randomly
      assigned to seven groups (n 6 per group). The groups differed in diet and day of
      dissection. On the day of weaning, dissection was performed on one group of six
      piglets. The remaining groups were fed one of three experimental diets in which
      glucose, lactose or starch had been iso-energetically exchanged, supplying 24%
      dietary energy. The piglets received a liquid diet (air-dry meal:water of 1:2,
      w/w). The piglets were given access to a maximum of dietary energy in order to
      prevent confounding between feed intake and villus architecture. The piglets were
      dissected and sampled on days 0, 3, or 10 post-weaning. The results show that the
      carbohydrate source did not affect growth performance, organ weights, villus
      architecture, pH of chyme and plasma haptoglobin level. The weaning transition
      resulted in decreased villus height and increased haptoglobin levels. In the
      contents of the caecum and large intestine, the pH decreased after weaning. It is
      concluded that at least under conditions of similar feed intake and low
      infectious pressure, dietary lactose does not ameliorate the weaning-induced
      compromise of small-intestinal integrity when compared with either glucose or
      starch.

PMID- 14667185
TI  - Dietary conjugated linoleic acid differentially alters fatty acid composition and
      increases conjugated linoleic acid content in porcine adipose tissue.
AB  - Conjugated linoleic acids (CLA) have been shown to decrease body fat content in
      pigs. It is possible that feeding pigs diets rich in CLA may increase carcass
      lipid CLA to levels that could provide health benefits when included as a part of
      a healthy diet. Therefore, the aim of the present study was to determine whether
      dietary CLA supplementation has any effect on the fatty acid composition of
      subcutaneous and intramuscular adipose tissue in pigs. Thirty-five female cross
      bred (Large White x Landrace) pigs (initial weight 57.2 kg and initial P2 back
      fat 11.5 mm) were used in the present study. Pigs were housed individually and
      randomly allocated to one of six dietary treatments (0.00, 1.25, 2.50, 5.00, 7.50
      and 10.00 g CLA55 (55 g CLA isomers/100 g total fatty acids; Natural Lipids Ltd,
      Hovdebygda, Norway)/kg) and fed their respective diets for 8 weeks. Twelve CLA
      isomers in the diet and in pig tissue lipids were separated by Ag+-HPLC. CLA was
      incorporated at fivefold higher levels in subcutaneous fat as compared with
      intramuscular fat and in a dose-dependant manner. Overall, the transfer
      efficiency of CLA was maximized at 5.00 g CLA55/kg. However, there was clear
      selectivity in the uptake or incorporation of cis,trans-9,11 isomer over the
      trans,cis-10,12 isomer. In general, CLA supplementation produced significant
      changes in skeletal muscle and adipose tissue fatty acid composition, indicating
      that dietary CLA had a potent affect on lipid transport and metabolism in vivo.
      Significant increases in myristic, palmitic and palmitoleic acids and a reduction
      in arachidonic acid were observed, suggesting an alteration in activity of delta5
      , delta6- and delta9-desaturases in pig adipose tissue. In conclusion, feeding
      pigs diets supplemented with CLA increases carcass lipid CLA, but also results in
      changes in the fatty acid profile in pig fat that could potentially outweigh the
      benefits of CLA.

PMID- 14667186
TI  - Effect of insulin-like growth factor-I on nitrogen balance and intestinal
      galactose transport in rats with moderate liver cirrhosis.
AB  - The malnutrition caused by liver cirrhosis (LC) often worsens the course of the
      disease. Patients affected by LC often have a low bioavailability of the anabolic
      liver peptide insulin-like growth factor (IGF)-I. The present study was
      undertaken to investigate the effect of low doses of IGF-I on the nutritional
      status and in vivo jejunal transport of D-galactose in anatomically,
      pathologically and biochemically confirmed moderate, non-ascitic, cirrhotic rats.
      LC was experimentally induced in growing rats by inhalation of CCl4 and addition
      of phenobarbital to drinking water. Both the nutritional status, as evaluated by
      N balance, and in vivo intestinal transport of D-galactose, were significantly
      impaired in cirrhotic rats. As compared with healthy rats, administration of 20
      microg human recombinant IGF-I/kg body weight for 14 d to cirrhotic rats
      significantly improved N balance variables and restored in vivo intestinal
      transport of the sugar. However, IGF-I had no effect on the steatorrhoea
      associated with LC. These results suggest that low doses of IGF-I may have
      beneficial effects on the malnutrition associated with moderate LC.

PMID- 14667187
TI  - Effects of intraruminal propionate supplementation on nitrogen utilisation by the
      portal-drained viscera, the liver and the hindlimb in lambs fed frozen rye grass.
AB  - The influence of propionate supplementation on the splanchnic metabolism of amino
      acids (AA) and other N compounds (urea-N and NH3-N) and the supply of AA and NH3
      N to the hindlimb was investigated in growing lambs. Six rumen-cannulated and
      multicatheterised lambs (32.2 kg) were fed frozen rye grass at 690 kJ
      metabolisable energy intake/d per kg average metabolic body weight. They were
      infused intraruminally with a salt solution (control) or with propionate
      solutions at 0.23 mol/l (P1) or 0.41 mol/l (P2) infused at a maximal rate of 1.68
      (SD 0.057) ml/min according to a repeated Latin square design. The propionate
      infusion did not increase the net portal appearance of total AA (TAA)-N but
      increased that of some branched-chain AA (valine and to a lesser extent
      isoleucine). Simultaneously, the propionate treatment (especially P2) induced an
      increased TAA utilisation by the liver. This was due mainly to an increased
      (+79%; P<0.07) utilisation of the essential AA and particularly the branched
      chain AA. A stimulation of protein synthesis in the liver is hypothesised since
      (1) propionate stimulated insulin secretion and (2) utilisation of non-essential
      AA were less influenced by the propionate treatment in the liver (except for
      alanine), suggesting that the AA utilised by the liver were directed towards
      protein synthesis rather than towards oxidation or urea synthesis. At the
      splanchnic level, the propionate treatment did not have any effect on the TAA,
      non-essential AA and essential AA, except for a net splanchnic release that was
      decreased for leucine (P<0.02) and methionine (P<0.01) and increased for
      threonine (P<0.05). The propionate treatment did not have any effect on the
      hindlimb uptake of AA (essential and non-essential). As a consequence, even
      though the propionate treatment induced some major alterations in the splanchnic
      metabolism of AA, there were no changes in the net AA balance in the hindlimb
      (and hence probably on muscle growth). The role of the splanchnic tissues in the
      regulation of the AA supply to the peripheral tissues (such as muscle) therefore
      appears to be prominent in the regulation of muscle growth. Whether the
      peripheral tissues regulate their own supply by interacting with the splanchnic
      tissues (and especially the liver) or the liver is the only regulator of the AA
      supply to the muscle remains in doubt.

PMID- 14667188
TI  - Effect of high-fat feeding on metabolic efficiency and mitochondrial oxidative
      capacity in adult rats.
AB  - The changes in metabolic efficiency, body composition, and nutrient partitioning
      induced by high-fat feeding were evaluated in adult rats (90 d of age). The
      alterations in serum free triiodothyronine, insulin, and leptin levels, as well
      as in hepatic and skeletal muscle metabolism, were also assessed. Rats were fed
      either a low- or a high-fat diet for 2 weeks. Relative to the low-fat feeding,
      energy intake and expenditure, as well as body-energy gain, lipid gain, and
      energetic efficiency, were increased by the high-fat feeding. Increased serum
      leptin levels accompanied these variations. A positive correlation between serum
      leptin levels and percentage of body fat was found in the rats fed the low- or
      high-fat diet, with a significant divergence between the slope of the regression
      lines. Furthermore, a negative correlation between serum leptin level and energy
      intake was found in the rats fed the low-fat diet, while a positive correlation
      was found in the rats fed the high-fat diet. Finally, the high-fat feeding
      decreased the hepatic and skeletal muscle mitochondrial oxidative capacity. It is
      concluded that, in adult rats, a nutritional factor such as a high level of fat
      in the diet induces obesity, leptin resistance, and impairment of mitochondrial
      capacity, all phenomena typical of unrestrained aged rats.

PMID- 14667189
TI  - Comparison of commonly used procedures, including the doubly-labelled water
      technique, in the estimation of total energy expenditure of women with special
      reference to the significance of body fatness.
AB  - According to the report of the World Health Organization (1985), total energy
      expenditure (TEE) in human subjects can be calculated as BMR x physical activity
      level (PAL). However, other reports have pointed out limitations in the suggested
      procedure related to the % body fat of the subjects. The purpose of the present
      study was to evaluate the World Health Organization (1985) procedure in thirty
      four healthy women with BMI 18-39 kg/m2. BMR and TEE were measured using indirect
      calorimetry (BMRmeas) and the doubly-labelled water method (TEEref) respectively.
      When assessed using the doubly-labelled water and skinfold-thickness methods, the
      women had 34 (SD 8) and 33 (SD 6) % body fat respectively. On the basis of
      guidelines provided by the World Health Organization (1985), 1.64 was selected to
      represent the average PAL of the women. Furthermore, PAL was also assessed by
      means of an accelerometer (PALacc), heart-rate recordings (PAL(HR)) and a
      questionnaire (PALq). These estimates were: PALacc 1.71 (SD 0.17), PAL(HR) 1.76
      (SD 0.24), PALq 1.86 (SD 0.27). These values were lower than TEEref/BMRref, which
      was 1.98 (SD 0.21). BMR assessed using equations recommended by the World Health
      Organization (1985) (BMRpredicted) overestimated BMR by 594 (SD 431) kJ/24 h.
      However, when TEE was calculated as BMRpredicted x PALacc, BMRpredicted x PAL(HR)
      and BMRpredicted x PALq respectively, average results were in agreement with
      TEEref. Furthermore, TEE values based on BMRpredicted and PALacc, PAL(HR), PALq
      as well as on PAL = 1.64, minus TEEref, were significantly correlated with body
      fatness. When the same PAL value (1.64) was used for all subjects, this
      correlation was particularly strong. Thus, the World Health Organization (1985)
      procedure may give TEE results that are biased with respect to the body fatness
      of subjects.

PMID- 14667191
TI  - Infant intake of fatty acids from human milk over the first year of lactation.
AB  - Despite the importance of human milk fatty acids for infant growth and
      development, there are few reports describing infant intakes of individual fatty
      acids. We have measured volume, fat content and fatty acid composition of milk
      from each breast at each feed over a 24 h period to determine the mean daily
      amounts of each fatty acid delivered to the infant from breast milk at 1, 2, 4,
      6, 9 and 12 months of lactation in five women. Daily (24 h) milk production was
      336.60 (SEM 26.21) and 414.49 (SEM 28.39) ml and milk fat content was 36.06 (SEM
      1.37) and 34.97 (SEM 1.50) g/l for left and right breasts respectively over the
      course of the first year of lactation. Fatty acid composition varied over the
      course of the day (mean CV 14.3 (SD 7.7) %), but did not follow a circadian
      rhythm. The proportions (g/100 g total fatty acids) of fatty acids differed
      significantly between mothers (P<0.05) and over the first year of lactation
      (P<0.05). However, amounts (g) of most fatty acids delivered to the infant over
      24 h did not differ during the first year of lactation and only the amounts of
      18:3n-3, 22:5n-3 and 22:6n-3 delivered differed between mothers (P<0.05). Mean
      amounts of 18:2n-6, 18:3n-3, 20:4n-6 and 22:6n-3 delivered to the infant per 24 h
      over the first year of lactation were 2.380 (SD 0.980), 0.194 (SD 0.074), 0.093
      (SD 0.031) and 0.049 (SD 0.021) g respectively. These results suggest that
      variation in proportions of fatty acids may not translate to variation in the
      amount delivered and that milk production and fat content need to be considered.

PMID- 14667190
TI  - Mitochondrial energy metabolism in a model of undernutrition induced by
      dexamethasone.
AB  - The present investigation was undertaken to evaluate whether mitochondrial energy
      metabolism is altered in a model of malnutrition induced by dexamethasone (DEX)
      treatment (1.5 mg/kg per d for 5 d). The gastrocnemius and liver mitochondria
      were isolated from DEX-treated, pair-fed (PF) and control (CON) rats. Body weight
      was reduced significantly more in the DEX-treated group (-16%) than in the PF
      group (-9%). DEX treatment increased liver mass (+59% v. PF, +23% v. CON) and
      decreased gastrocnemius mass. Moreover, in DEX-treated rats, liver mitochondria
      had an increased rate of non-phosphorylative O2 consumption with all substrates
      (approximately +42%). There was no difference in enzymatic complex activities in
      liver mitochondria between rat groups. Collectively, these results suggest an
      increased proton leak and/or redox slipping in the liver mitochondria of DEX
      treated rats. In addition, DEX decreased the thermodynamic coupling and
      efficiency of oxidative phosphorylation. We therefore suggest that this increase
      in the proton leak and/or redox slip in the liver is responsible for the decrease
      in the thermodynamic efficiency of energy conversion. In contrast, none of the
      variables of energy metabolism determined in gastrocnemius mitochondria was
      altered by DEX treatment. Therefore, it appears that DEX specifically affects
      mitochondrial energy metabolism in the liver.

PMID- 14667192
TI  - Evaluation of two foot-to-foot bioelectrical impedance analysers to assess body
      composition in overweight and obese adolescents.
AB  - The objective of the present study was to determine the accuracy of two foot-to
      foot (FF) bioelectrical impedance analysers (BIA) to assess body composition in
      overweight and obese adolescents, compared with dual-energy X-ray absorptiometry
      (DXA) and hand-to-foot (HF) BIA. Body composition was assessed in fifty-three
      overweight or obese adolescents (BMI 27.9 (SD 4.1) kg/m2; aged 13-16 years) by
      DXA (Hologic QDR-4500; Hologic Inc., Bedford, MA, USA) and BIA (HF (BIA 101, RJL
      System, Detroit, IL, USA) and FF (Body Fat Monitor Scale BF-625, Tanita
      Corporation of America Inc., Arlington Heights, IL, USA; Tefal Bodymaster Vision,
      Tefal, Rumilly, France)). Bland-Altman tests showed that, compared with DXA, FF
      Tanita and FF-Tefal underestimated (P<0.05) fat mass (FM) less than HF-BIA (-1.7
      (SD 3.1), -0.7 (SD 5.8) and -2.3 (SD 2.2) kg respectively, P<0.001). However, the
      limits of agreement between DXA and FF-Tanita or FF-Tefal were much greater than
      those obtained with HF-BIA (-7.7 and +4.3, - 12.0 and +10.6 v. -2.1 and +6.7 kg
      respectively). The differences between FM assessed using the FF-Tanita or the FF
      Tefal analyser and DXA increased with the waist:hip ratio, and were higher in
      boys than in girls. The major limiting factor of FF-BIA was the inter-individual
      variability in FM estimates. In conclusion, FF-BIA and DXA are not
      interchangeable methods. FF-BIA could be acceptable to assess body composition in
      large groups of overweight or obese adolescents, but cannot be recommended for
      body composition assessment in obese subjects because of the large errors in
      individual estimates.

PMID- 14667193
TI  - n-3 fatty acid metabolism in women.

PMID- 14667194
TI  - Prevention of life-threatening infections due to encapsulated bacteria in
      children with hyposplenia or asplenia: a brief review of current recommendations
      for practical purposes.
AB  - The aim of the present work was to summarise in a single paper all the options
      for prevention of life-threatening infections due to encapsulated bacteria in
      patients with hyposplenism or asplenia. Prevention of these infections should be
      obtained in all patients with 1) patient and family education, 2) prophylaxis by
      means of vaccination against Haemophilus influenzae and Streptococcus pneumoniae,
      3) antibiotic prophylaxis, based primarily on penicillin, 4) delay of elective
      splenectomy or use methods of tissue salvage in splenic trauma. Vaccination is
      not effective against all serotypes of S. pneumoniae and Neisseria meningitidis
      causing life-threatening infections in hypo/asplenic patients. Moreover,
      antibacterial prophylaxis could select antibacterial-resistant pathogens and is
      highly conditioned by patient's compliance. Therefore, empirical antibacterial
      therapy of fever and/or suspected infection should be recommended to all
      splenectomised patients independently from time elapsing from splenectomy,
      vaccinal status and assumption of antibacterial prophylaxis.

PMID- 14667195
TI  - Bulky disease is the most important prognostic factor in Hodgkin lymphoma stage
      IIB.
AB  - The aim of this study was to evaluate treatment results for Hodgkin lymphoma (HL)
      patients younger than 60 yr in stage IIB, treated according to the Swedish
      National Care Programme. The intention was also to identify specific subgroups
      depending on the number of negative prognostic factors the patients have, in
      order to optimise and differentiate future treatment. In total, 99 patients with
      HL stage IIB, diagnosed between 1985 and 1994, have been analysed. There were 47
      men and 52 women and the median age was 33 yr (range 17-59). Eighty-six patients
      presented with supradiaphragmatic disease and 13 with infradiaphragmatic. The HL
      specific and overall 10-yr survival was 73 and 65%, respectively. The HL-specific
      survival for patients in pathological stage IIB tended to be better, although not
      statistically significant than for clinical stage IIB, despite less chemotherapy
      (P = 0.1). The patients in stage IIB who were selected for laparotomy were,
      however, younger and with fewer negative prognostic factors. The only significant
      negative prognostic factor was bulky disease (P = 0.001). The following factors
      also tended to have a negative influence on the prognosis although not
      statistically significant: the International Prognostic Score, the number of
      involved lymph node stations, extranodal involvement and leucocyte count > 15 x
      10(9)/L. In conclusion, we suggest that bulky disease should be taken into
      account when treating patients with stage IIB HL.

PMID- 14667196
TI  - Telomere shortening in patients with plasma cell disorders.
AB  - OBJECTIVES: Telomeres are essential for maintaining chromosomal integrity; their
      shortening is associated with chromosome instability. The aim of this work was to
      study telomere length (TL) on bone marrow (BM) cells from patients with multiple
      myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).
      METHODS: Thirty-one MM patients: 12 at diagnosis (D), 11 at relapse (R) and eight
      at remission (RE) and two cases with MGUS were studied. TL based on terminal
      restriction fragment (TRF) assay was evaluated. Cytogenetic and molecular
      cytogenetic analyses were performed. Telomeric associations (TAs) on BM
      metaphases were also studied. RESULTS: TRF analysis in total MM patients showed a
      mean TRF peak value (5.20 +/- 0.35 kb) shorter than those observed in controls
      (8.5 +/- 0.5 kb) (P < 0.001). Moreover, TRF at D and R showed a significant
      telomere shortening (P < 0.001), with TL restored at RE. A strong correlation
      with the percentage of BM plasma cell infiltration (BMPCI) (rK = -0.540; P =
      0.002) was found. Patients with abnormal karyotypes (AK) had significantly
      shorter TRFs than that observed in MM patients with normal karyotypes (P < 0.05).
      TRFs in MGUS patients did not differ with respect to controls. TA analysis showed
      an increased percentage in MM (19.46 +/- 1.98%) with respect to MGUS (6.12 +/-
      1.87%) and normal BM cells (2.00 +/- 0.93%) (P < 0.001). CONCLUSIONS: MM patients
      showed a significant reduction in TL (> 60% of BMPCI and AK), suggesting a
      probable association with clinical evolution. Moreover, our findings support the
      idea that telomere shortening usually leads to increased frequencies of TAs and
      chromosome instability.

PMID- 14667197
TI  - Multiparametric analysis of immature cell populations in umbilical cord blood and
      bone marrow.
AB  - Adult stem cells are finding increased therapeutic potential not least in tissue
      regeneration protocols. The cell sources being proposed for such protocols
      include embryonic, umbilical cord blood (CB) and adult bone marrow (BM). Although
      embryonic sources are controversial, CB and marrow are available immediately. The
      appropriate cells of use in these sources are considered to be extremely rare and
      a characterisation of the starting cell source is important for the development
      of adult stem cell protocols and ex vivo expansion. Umbilical CB and BM
      mononuclear cells were labelled for the antigens CD34, CD133, CD117, CD164, Thy-1
      or CD38, and additional intracellular CD34 antigen. Three dimensional flow
      cytometric analyses were carried out together with dual laser confocal microscope
      analysis for antigen profile expression. Variable levels of immaturity were
      detected on CB and BM populations using internal and external CD34 antigen. For
      CB and BM cells, internal CD34 (intCD34+) could be detected on co-expressing
      CD133+ cells before expression of external CD34 antigen (extCD34+). CD38 co
      expression analysis also showed that a small but distinct group of cells
      expressing low CD38 and no external CD34 antigen could be detected. Additional
      phenotyping of these cells using CD117, Thy-1, CD164 and CD133 demonstrated
      variable primitive status detectable within the external CD34- population. Newly
      harvested primary CB and BM populations were shown to contain not only cellular
      populations of known standard sequential maturity but also populations of more
      extreme rarity. The presence of cells which lacked extracellular CD34 antigen, in
      both CB and BM, but which possessed CD133, has important implications for
      purification of human stem cells in clinical applications.

PMID- 14667198
TI  - Correlation of c-kit expression and cell cycle regulation by transforming growth
      factor-beta in CD34+ CD38- human bone marrow cells.
AB  - To investigate the relationship between c-kit expression and cell cycle
      regulation by endogenous transforming growth factor-beta (TGF-beta) in human bone
      marrow hematopoietic progenitor cells, CD34+ CD38- c-kit(low/-) and CD34+ CD38- c
      kit(high) populations were cultured in stem cell factor, thrombopoietin,
      interleukin-3 (IL-3), IL-6, granulocyte colony-stimulating factor,
      granulocyte/macrophage colony-stimulating factor and anti-TGF-beta, and analyzed
      for cell cycle status. Arrest in G0/G1 was most prominent in the precultured
      CD34+ CD38- c-kit(low/-) subset (95.62 +/- 4.15%). While postcultured CD34+ CD38-
      c-kit(high) cells initiated from CD34+ CD38- c-kit(high) cells entered cell cycle
      within 36 hr, postcultured CD34+ CD38- c-kit(low/-) cells initiated from CD34+
      CD38- c-kit(low/-) cells remained dormant until 36 hr and entered cell cycle
      within 90 hr. Anti-TGF-beta increased the percentage of S/G2M phase postcultured
      CD34+ CD38- c-kit(high) cells (from 19.08 +/- 11.95 to 47.04 +/- 2.93%), but no
      significant change was observed in postcultured CD34+ CD38- c-kit(low/-) cells.
      These results suggest that endogenous TGF-beta plays an important role in the
      cell cycle arrest of c-kit(high) but not c-kit(low/-) cells in CD34+ CD38- cells,
      which proliferate without undergoing differentiation. The different regulatory
      mechanism of cell cycle entry of the CD34+ CD38- c-kit(high) and CD34+ CD38- c
      kit(low/-) subsets might be the result of differences in their sensitivity to
      endogenous TGF-beta.

PMID- 14667200
TI  - Low L-selectin (CD62L) expression in acute myeloid leukemia correlates with a bad
      cytogenetic risk.
AB  - OBJECTIVES: Interactions between hemopoietic cells and the stromal
      microenvironment or immunoreactive cells are mediated by specific cell surface
      receptors. The expression of those molecules may alter the adhesive qualities
      (mobility and homing) as well as immune response behavior of leukemic blasts. L
      Selectin (CD62L) is suggested to play a role in the redistribution and homing of
      hemopoietic progenitor cells to the bone marrow (BM). Down-regulation of L
      selectin is responsible for mobilization of blasts from the BM into the
      circulation and ligation of L-selectin stimulates proliferation of progenitor
      cells. This could have an influence on the process of leukemia. METHOD: We have
      studied the expression of L-selectin on mononuclear BM cells of 36 acute myeloid
      leukemia (AML) patients at first diagnosis by FACS analysis using a directly
      fluorescein isothiocyanate conjugated antibody (clone DRE G56). RESULTS: On
      average the patients presented with 88% blasts in the BM. The expression tended
      to be higher in primary (p) AML compared with secondary (s) AML. L-Selectin was
      very heterogenously expressed in all FAB groups. Highest expression was found in
      cases with AML-M4 with four of nine cases presenting with an inv(16) karyotype.
      Separating our patient cohort in cytogenetic risk groups we could detect a
      significantly higher expression of L-selectin in cases with a 'good risk'
      karyotype and a very low expression in cases with a 'bad risk' karyotype (P =
      0.037). Comparing patients who achieved remission after double induction therapy
      (responders) with patients who showed persisting disease (non-responders) we
      found a higher percentage of L-selectin+ cases or cells in the responder group
      than in the non-responder group, although the differences were not significant
      because of only five cases in the 'non-responder' group. Evaluating cut-off
      points greatest differences in relapse-free survival probabilities were found in
      patients who presented with > or = 30% L-selectin+ BM cells compared with cases
      with < 30%: 86% of cases with > or = 30% L-selectin+ cells were still in
      remission after a mean follow up time of only 8 months compared with only 46% in
      the group with < 30% L-selectin+ cells. CONCLUSIONS: We can conclude that (i)
      expression of L-selectin on AML blasts is variable. This reveals the great
      diversitiy of immunophenotypes in AML and might contribute to identify individual
      blast phenotypes in order to detect minimal residual disease in remission. (ii)
      Low L-selectin expression correlates with a bad cytogenetic risk, with a lower
      probability to achieve remission and with a shorter relapse-free survival time.
      This might reflect a decreased homing of the blasts to the BM as well as an
      impaired cytotoxic T-cell reaction against leukemic cells. The expression of L
      selectin on leukemic blasts might be influenced by different cytokine therapies
      (e.g. with interferon alpha) and this might result in an altered hematologic
      reconstitution after cytotoxic therapies as well as in an altered immunologic
      recognition of blasts.

PMID- 14667199
TI  - Effects of anoxia on megakaryocyte progenitors derived from cord blood CD34pos
      cells.
AB  - BACKGROUND: Severe hypoxic insults to the fetus and neonate are associated with
      the development of thrombocytopenia. The thrombocytopenia in some cases is the
      result of disseminated intravascular coagulation, but that mechanism fails to
      account for all, perhaps the majority, of cases. OBJECTIVE: We hypothesized that
      human fetal megakaryocyte (Mk) progenitors are directly adversely affected by
      transient anoxia. DESIGN AND METHODS: To test this, we isolated CD34pos cells
      from the umbilical cord blood of 10 healthy term neonates, and exposed these to
      0% or 20% O2 for 24 h, with or without recombinant thrombopoietin (rTpo, 50
      ng/mL). After 24 h, a portion of the CD34pos cells were harvested for flow
      cytometric evaluation of apoptosis. The remaining cells were cultured for an
      additional 10-12 days, under normoxic conditions, in a collagen-based serum-free
      system containing rTpo, IL-3, and IL-6. In this way, we sought to determine the
      effect of transient anoxia on clonogenic capacity of Mk progenitors. RESULTS:
      Contrary to our hypothesis, anoxia did not increase either apoptosis or cell
      death of the CD34pos cells. The addition of rTpo was protective, with a
      significant decrease in apoptosis and cell death (P < 0.0001), and an increase in
      the number of Mk colonies cultured (P = 0.04). There was no difference between
      the normoxic and anoxic groups in proliferative potential of the Mk progenitor
      cells. CONCLUSIONS: The thrombocytopenia observed in neonates following an acute
      hypoxic event is not likely due to a direct deleterious effect of hypoxia on Mk
      progenitors.

PMID- 14667201
TI  - Elevated plasma levels of TIMP-1 correlate with plasma suPAR/uPA in patients with
      chronic myeloproliferative disorders.
AB  - Chronic myeloproliferative disorders (MPD) are characterized by progressive
      remodelling of bone marrow stroma as evidenced by increased deposition of
      extracellular matrix proteins, neoangiogenesis and displacement of normal
      haematopoietic cells by fibrotic tissue. The family of metalloproteinases (MMPs)
      and tissue inhibitors of metalloproteinase (TIMPs) serve to facilitate and
      inhibit matrix degradation processes, respectively. In an attempt to investigate
      potential markers for bone marrow remodelling processes, we investigated plasma
      levels of total-, free- and complexed TIMP-1, TIMP-2, MMP-2 and MMP-9 in a
      patient cohort comprising 17 with myelofibrosis (MF), 17 with polycythaemia vera
      (PV), 15 with essential thrombocythaemia (ET), 1 with a transitional MPD and 30
      controls. Compared with controls, total- (P < 0.0001) (median: 132.6 microg/L vs.
      80.8 microg/L), free- (P < 0.0001) (median: 126.4 microg/L vs. 65.8 microg/L) and
      complexed TIMP-1 (P = 0.0009) (median: 17.7 microg/L vs. 10.7 microg/L)
      concentration was significantly higher in the patients. TIMP-1 was significantly
      correlated with plasma soluble urokinase plasminogen activator receptor (P =
      0.003) and urokinase plasminogen activator (P < 0.0001), respectively, suggesting
      a common cellular origin. No statistical significant difference between TIMP-2
      and MMP-2 levels was observed between patients and controls. Furthermore, a
      significant correlation between free TIMP-1 and TIMP-2 levels was detected (r =
      0.56; P < 0.0001). Median MMP-9 concentration was significantly higher among PV
      patients compared with controls (P = 0.0015), and 41% of patients with PV (7/17)
      had MMP-9 values that were above the mean + 2SD of plasma MMP-9 levels found in
      controls. The ratio of total TIMP-1/MMP-9 was significantly higher in patients
      with MF compared with controls (P = 0.0004). These findings suggest that a
      disturbed TIMP-1/MMP ratio may reflect an imbalance of the extracellular
      homeostasis towards an increased matrix deposition promoting fibrosis.

PMID- 14667202
TI  - A 29-yr-old man with multiple myeloma presenting with subcutaneous masses.
AB  - We report the case of a 29-yr-old man with multiple myeloma who presented
      initially with subcutaneous plasmacytomas. These are the atypical features of his
      clinical course: (a) age of the patient; (b) unusual clinical presentation with
      subcutaneous masses; (c) lack of 'typical' features of multiple myeloma (renal
      failure, hypercalcaemia, and bone pain); and (d) disease progression as
      extramedullary recurrences.

PMID- 14667203
TI  - Hydroxyurea-induced pneumonitis in a patient with chronic idiopathic
      myelofibrosis after prolonged drug exposure.
AB  - We describe a 63-yr-old patient diagnosed with chronic idiopathic myelofibrosis
      whose disease was treated with hydroxyurea for 2 yr. He developed respiratory
      symptoms that were extensively investigated including lung biopsy. Clinical,
      radiological and histological features were compatible with a diagnosis of
      hydroxyurea-induced pneumonitis. Following drug withdrawal there was remarkable
      improvement in clinical and radiological findings.

PMID- 14667204
TI  - Ursodeoxycholic acid treatment of idiopathic thrombocytopenic purpura with liver
      dysfunction.
AB  - Ursodeoxycholic acid (UDCA) is known to reduce immunoglobulin from B cells and
      cytokine production from T cells. We found that UDCA increased the platelet count
      in two idiopathic thrombocytopenic purpura (ITP) patients who have liver
      dysfunction. UDCA was tolerated and did not cause diarrhea in the amounts used.
      Further investigation is needed to evaluate the effectiveness of UDCA in ITP
      patients.

PMID- 14667205
TI  - Shwachman-Diamond syndrome with late-onset neutropenia and fatal acute myeloid
      leukaemia without maturation: a case report.
AB  - We report on a male patient affected by Shwachman Diamond syndrome (SDS) who
      presented an unusual delayed neutropenia and then developed a poorly
      differentiated acute myeloid leukaemia (M0-AML) with trilineage myelodysplasia in
      adulthood. Conventional cytogenetics revealed complex karyotypic changes
      (monosomies 20, 21, 22, additional 15p). The patient was treated with
      conventional chemotherapy but never reached complete remission of leukaemia and
      died 18 months after diagnosis. SDS is an inherited bone marrow failure syndrome
      with a high propensity to leukaemic transformation. Since neutropenia may be
      intermittent or with delayed onset, and leukaemic transformation may not occur
      until adulthood, full blood count should be regularly monitored in such patients.

PMID- 14667206
TI  - Aplastic anemia following administration of a tumor necrosis factor-alpha
      inhibitor.
AB  - Upregulation of tumor necrosis factor-alpha (TNF-alpha) has been implicated in
      the pathogenesis of several inflammatory conditions, including rheumatoid
      arthritis. Therapeutic agents such as antibodies or soluble TNF-alpha receptor
      analogs, which block TNF-alpha activity are a recent addition to the therapeutic
      armamentarium for the conditions. We describe a patient who developed aplastic
      anemia complicated by sepsis after receiving etanercept, a TNF-alpha receptor
      analog, for the treatment of rheumatoid arthritis. Pancytopenia resolved within 3
      wk of discontinuing etanercept. To our knowledge, this is the first report of
      aplastic anemia associated with TNF-alpha blockade.

PMID- 14667207
TI  - Hyperdiploid karyotype in a child with hypocellular primary myelodysplastic
      syndrome.

PMID- 14667208
TI  - Design and synthesis of novel bioactive peptides and peptidomimetics.

PMID- 14667209
TI  - Synthesis, in vitro affinity, and efficacy of a bis 8-ethynyl-4H-imidazo[1,5a]-
      [1,4]benzodiazepine analogue, the first bivalent alpha5 subtype selective
      BzR/GABA(A) antagonist.
AB  - The synthesis and in vitro affinity of the alpha5beta3gamma2 (alpha5) subtype
      selective BzR/GABA(A) antagonist 7 is described. This ligand is selective for
      alpha5 subtypes in vitro and is a potent antagonist of the effects of diazepam
      only at alpha5beta3gamma2 subtypes (oocytes). Ligands such as 7 will be important
      in the determination of which physiological function(s) are subserved by this
      GABA(A) alpha5 subtype.

PMID- 14667210
TI  - Systematic surface scan of the most favorable interaction sites of magnesium ions
      with tetracycline.
AB  - AM1 semiempirical molecular orbital calculations have been used to probe the
      complexation sites for naked and hydrated magnesium ions to the different
      conformations and protonation states of tetracycline. The calculations reveal a
      wealth of possible magnesium complexation sites within a small energy range, but
      also indicate that magnesium complexation does not change the conformational
      behavior of tetracycline significantly. A hitherto unknown solvated conformation
      is suggested for deprotonated tetracycline.

PMID- 14667211
TI  - Enantioselective responses to a phosphorothioate analogue of lysophosphatidic
      acid with LPA3 receptor-selective agonist activity.
AB  - The metabolically stabilized LPA analogue, 1-oleoyl-2-O-methyl-rac
      glycerophosphothioate (OMPT), is a potent agonist for the LPA(3) G-protein
      coupled receptor. A new enantiospecific synthesis of both (2R)-OMPT and (2S)-OMPT
      is described. Calcium release assays in both LPA(3)-transfected insect Sf9 and
      rat hepatoma Rh7777 cells showed that (2S)-OMPT was 5- to 20-fold more active
      than (2R)-OMPT. Similar results were found for calcium release, MAPK and Akt
      activation, and IL-6 release in human OVCAR3 ovarian cancer cells.

PMID- 14667212
TI  - Novel sst(4)-selective somatostatin (SRIF) agonists. 1. Lead identification using
      a betide scan.
AB  - Hypothesizing that structural constraints in somatostatin (SRIF) analogues may
      result in receptor selectivity, and aiming to characterize the bioactive
      conformation of somatostatin at each of its five receptors, we carried out an
      N(beta)-methylated aminoglycine (Agl) scan of the octapeptide H-c[Cys(3)-Phe(6)
      Phe(7)-dTrp(8)-Lys(9)-Thr(10)-Phe(11)-Cys(14)]-OH (SRIF numbering) (ODT-8) that
      is potent at all SRIF receptor subtypes (sst's) but sst(1). We found that H-c[Cys
      LAgl(N(beta)Me,benzoyl)-Phe-DTrp-Lys-Thr-Phe-Cys]-OH (4), H-c[Cys-Phe
      LAgl(N(beta)Me,benzoyl)-Trp-Lys-Thr-Phe-Cys]-OH (6), H-c[Cys-Phe
      LAgl(N(beta)Me,benzoyl)-dTrp-Lys-Thr-Phe-Cys]-OH (8), and H-c[DCys-Phe
      LAgl(N(beta)Me,benzoyl)-DTrp-Lys-Thr-Phe-Cys]-OH (10) had high affinity (IC(50) =
      14.3, 5.4, 5.2, and 3.4 nM, respectively) and selectivity for sst(4) (>50-fold
      over the other receptors). The l-configuration at positions 7 and 8 (l(7), l(8))
      yields greater sst(4) selectivity than the l(7), d(8) configuration (6 versus 8).
      Peptides with the d(7), l(8) (7) and d(7), d(8) (9) configurations are
      significantly less potent at all receptors. H-c[Cys-Phe-Phe-DTrp-LAgl(betaAla)
      Thr-Phe-Cys]-OH (16), H-c[Cys-Phe-Phe-DTrp-DAgl(betaAla)-Thr-Phe-Cys]-OH (17),
      and their N(beta)Me derivatives at position 9 (18, 19) were essentially inactive.
      Potent but less sst(4)-selective were members of the Agl-scan at positions 10, H
      c[Cys-Phe-Phe-dTrp-Lys-lAgl(N(beta)Me,HO-Ac)-Phe-Cys]-OH (20, IC(50) = 6.5 nM),
      and 11, H-c[Cys-Phe-Phe-DTrp-Lys-Thr-LAgl(N(beta)Me,benzoyl)-Cys]-OH (22, IC(50)
      = 6.9 nM), while the d-configuration at positions 10 (21) and 11 (23) led to
      reduced affinity. One of our best analogues, 8, is an agonist when tested for its
      ability to inhibit forskolin-stimulated cAMP accumulation in sst(4)-transfected
      CCL39 cells (EC(50) = 1.01 nM). All Agl-containing analogues were first
      synthesized using unresolved Fmoc-Agl(N(beta)Me,Boc)-OH, and the diastereomers
      were separated using HPLC. Chiral assignment at the Agl-containing residue was
      subsequently done using enzymatic degradation and by de novo synthesis in the
      cases of H-c[Cys-Phe-DAgl(N(beta)Me,benzoyl)-DTrp-Lys-Thr-Phe-Cys]-OH (9) and H
      c[DCys-Phe-DAgl(N(beta)Me,benzoyl)-DTrp-Lys-Thr-Phe-Cys]-OH (11), starting with
      the papain-resolved Fmoc-DAgl(Boc). These results suggested that the orientation
      of side chains at position 6, 7, or 11 with respect to the side chains of
      residues 8 and 9 may be independently responsible for sst(4) selectivity.

PMID- 14667213
TI  - Novel sst(4)-selective somatostatin (SRIF) agonists. 2. Analogues with beta
      methyl-3-(2-naphthyl)alanine substitutions at position 8.
AB  - We present a family of human sst(4)-selective, high-affinity (IC(50) = 2-4 nM)
      cyclic somatostatin (SRIF) octapeptides. These peptides result from the
      substitution of dTrp(8) in H-c[Cys(3)-Phe(6)-Phe(7)-DTrp(8)-Lys(9)-Thr(10)
      Phe(11)-Cys(14)]-OH (SRIF numbering) (ODT-8) by one of the four conformationally
      biased stereoisomers of beta-methyl-3-(2-naphthyl)alanine (beta-Me2Nal). Whereas
      H-c[Cys-Phe-Phe-DNal-Lys-Thr-Phe-Cys]-OH (ODN-8, 2) has high affinity and
      marginal selectivity for human sst(3) (Reubi et al., Proc. Natl. Acad. Sci.
      U.S.A. 2000, 97, 13973-13978), H-c[Cys-Phe-Tyr-D-threo-beta-Me2Nal-Lys-Thr-Phe
      Cys]-OH (5) has high affinity for all sst's except for sst(1); H-c[Cys-Phe-Tyr-L
      threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH (6) has high affinity for sst(4) (IC(50) =
      2.1 nM), with more than 50-fold selectivity toward the other receptors. Analogues
      7 and 8, containing d- and l-erythro-beta-Me2Nal instead of the corresponding
      threo derivatives at position 8, are essentially inactive at all receptors.
      Substitution of Tyr(7) in 5 and 6 by Aph(7) resulted in 9 and 10 with similar
      affinity patterns overall yet lowered affinity. The substitution of DCys(3) for
      Cys(3) in 5 and 6 yielded H-c[DCys-Phe-Tyr-D-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]
      OH (11) and H-c[DCys-Phe-Tyr-L-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH (12), with
      biological profiles almost identical to those of their parents 5 and 6 (i.e.,
      high affinity for sst(2-5) for 11 and high affinity and selectivity for sst(4)
      for 12). Analogue 12, with high sst(4) affinity combined with the highest sst(4)
      selectivity among all tested compounds, is an agonist in the cAMP accumulation
      assay (EC(50) = 1.29 nM). Cold monoiodination of 12 yielded 14, with loss of
      sst(4) selectivity and loss of high affinity (IC(50) = 21 nM). Introduction of
      Tyr(2) in 9 and 10 and substitution of Cys(3) by dCys(3), to yield 15 and 16
      (IC(50) = 9.8 and 61 nM, respectively, for sst(4) and limited selectivity),
      failed to generate a high-affinity (125)iodinatable sst(4)-selective ligand.
      Substitution of Phe by Tyr at position 11 in H-c[DCys-Phe-Phe-L-threo-beta-Me2Nal
      Lys-Thr-Phe-Cys]-OH yielded 18 (IC(50) = 11.8 nM at sst(4)), with limited sst(4)
      selectivity (30-fold or greater at the other receptors) yet only slightly
      improved affinity over that of 14. Cold monoiodination of 18 yielded 20 (IC(50) =
      30 nM at sst(4) and high selectivity). Whereas we were able, in this study, to
      identify a new family of sst(4)-selective, high-affinity compounds, our
      additional goal, to identify highly potent and sst(4)-selective ligands amenable
      to (125)iodination, could not be achieved satisfactorily. On the other hand, some
      of the diastereomers identified in this study, such as 5, 11, 17, and 19, are
      very potent ligands at all receptors but sst(1).

PMID- 14667214
TI  - Novel sst(4)-selective somatostatin (SRIF) agonists. 3. Analogues amenable to
      radiolabeling.
AB  - After our discovery that H-c[Cys-Phe-Phe-DNal-Lys-Thr-Phe-Cys]-OH (ODN-8) had
      high affinity and marginal selectivity for human sst(3) (part 2 of this series:
      Erchegyi et al. J. Med. Chem., preceding paper in this issue)(11) and that H
      c[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-OH (ODT-8, 3) had high affinity and marginal
      selectivity for human sst(4), that H-c[Cys-Phe-Tyr-D-threo-beta-Me2Nal-Lys-Thr
      Phe-Cys]-OH had high affinity for all sst's except for sst(1), and that H-c[Cys
      Phe-Tyr-L-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH had high affinity for sst(4)
      (IC(50) = 2.1 nM), with more than 50-fold selectivity toward the other receptors
      (parts 1 and 2 of this series: Rivier et al. and Erchegyi et al. J. Med. Chem.,
      preceding papers in this issue), we found H-c[Cys-Phe-Phe-Trp-Lys-Thr-Phe-Cys]-OH
      (OLT-8, 2), H-c[Cys-Phe-Phe-L-threo-beta-MeTrp-Lys-Thr-Phe-Cys]-OH (4) and H
      c[Cys-Phe-Phe-D-threo-beta-MeTrp-Lys-Thr-Phe-Cys]-OH (5) to have very high
      affinity for sst(4) (IC(50) = 0.7, 1.8, and 4.0 nM, respectively) and 5- to 10
      fold selectivity versus the other sst's. From earlier work, we concluded that an
      l-amino acid at position 8 and a tyrosine or 4-aminophenylalanine substitution at
      position 7 may lead to high sst(4) selectivity. In fact, [Tyr(7)]-2 (6) and
      [Tyr(7)]-3 (7) show ca. 5-fold selectivity for sst(4), and [Aph(7)]-2 (8) and
      [Aph(7)]-3 (9) have high sst(4) affinity (IC(50) = 1.2 and 0.88 nM, respectively)
      and selectivity, suggesting that indeed an l-residue at position 8 will direct
      selectivity toward sst(4). Unexpectedly, [Ala(7)]-2 (10) and [Ala(7)]-3 (11) have
      very high sst(4) affinity (IC(50) = 0.84 and 0.98 nM, respectively) and
      selectivity (>600- and 200-fold, respectively). The combination of Tyr(2) and
      dTrp(8) in analogues 14 and 22 did not affect the affinity of the analogues for
      sst(4) (IC(50) = 1.2 and 1.1 nM, respectively) but resulted in loss of
      selectivity, whereas the combination of Tyr(2) and LTrp(8) in H-Tyr-c[Cys-Phe-Aph
      Trp-Lys-Thr-Phe-Cys]-OH (13) and H-Tyr-c[Cys-Phe-Ala-Trp-Lys-Thr-Phe-Cys]-OH(19)
      retained high affinity (IC(50) = 1.9 and 1.98 nM, respectively) and sst(4)
      selectivity (>50 and >250, respectively). Interestingly, the same substitutions
      at positions 2 and 7, with l-threo-beta-MeTrp at position 8, yielded a much less
      selective analogue (20). Carbamoylation of the N-terminus of most of these
      analogues resulted in slightly improved affinity, selectivity, or both. Other
      amino acid substitutions in this series, such as those with Amp (25, 26), Orn
      (27), or IAmp (29) at position 7, were also tolerated but with a 2- to 3-fold
      loss of affinity and concomitant loss of selectivity. Analogous peptides with a
      tyrosine at position 11 (31-36) were less selective than the corresponding
      peptides with a tyrosine at position 2. Several analogues in this series compared
      favorably with the non-peptide L-803,087 (37) in terms of affinity and
      selectivity. Analogues 8, 10, and 21 potently inhibited the forskolin-stimulated
      cAMP production in sst(4)-transfected cells, therefore acting as full agonists.
      Cold monoiodination of 19 yielded 21, with retention of high sst(4) selectivity
      and affinity (IC(50) = 3.5 nM). (125)Iodinated 19 selectively binds to sst(4)
      transfected cells but not to sst(1-3)- or sst(5)-transfected cells. Binding in
      sst(4)-transfected cells was completely displaced by SRIF-28 or the sst(4)
      selective L-803,087.

PMID- 14667215
TI  - Novel sst(4)-selective somatostatin (SRIF) agonists. 4. Three-dimensional
      consensus structure by NMR.
AB  - The three-dimensional NMR structures of eight cyclic octapeptide analogues of
      somatostatin (SRIF) are described. These analogues, with the basic sequence H
      c[Cys(3)-Phe(6)-Xxx(7)-Yyy(8)-Lys(9)-Thr(10)-Zzz(11)-Cys(14)]-OH (the numbering
      refers to the position in native SRIF), with Xxx(7) being Phe/Ala/Tyr, Yyy(8)
      being Trp/DTrp/D-threo-beta-Me2Nal/L-threo-beta-Me2Nal, and Zzz(11) being
      Phe/Ala, exhibit potent and highly selective binding to human SRIF type 4
      (sst(4)) receptors. The conformations reveal that the backbones of these
      analogues do not have the usual type-II' beta-turn reported in the literature for
      sst(2)-subtype-selective analogues. Instead, the structures contain a unique
      arrangement of side chains of Yyy(8), Lys(9), and Phe(6) or Phe(11). The
      conformational preferences and results from biological analyses of these
      analogues (parts 1-3 of this series, Rivier et al., Erchegyi et al., and Erchegyi
      et al., J. Med. Chem. 2003, preceding papers in this issue) allow a detailed
      study of the structure-activity relationship of SRIF. The proposed consensus
      structural motif at the binding pocket for the sst(4)-selective analogues
      requires a unique set of distances between an indole/2-naphthyl ring, a lysine
      side chain, and another aromatic ring. This motif is necessary and sufficient to
      explain the binding affinities of all of the analogues studied and is distinct
      from the existing model suggested for sst(2)/sst(5) selectivity.

PMID- 14667216
TI  - Rational design of an indolebutanoic acid derivative as a novel aldose reductase
      inhibitor based on docking and 3D QSAR studies of phenethylamine derivatives.
AB  - A series of 45 phenethylamine derivatives were synthesized and evaluated for
      their inhibitory activity against pig kidney aldose reductase (ALR2, EC
      1.1.1.21). Their IC(50) values ranged from 400 microM to 24 microM. The binding
      modes of compounds at the active site of ALR2 were examined using flexible
      docking. The results indicated that phenethylamine derivatives nicely fit into
      the active pocket of ALR2 by forming various hydrogen bonding and hydrophobic
      interactions. 3D-QSAR analysis was also conducted using FlexX-docked alignment of
      the compounds. The best prediction was obtained by CoMSIA combined with
      hydrophobic and hydrogen bond donor/acceptor field (q(2) = 0.557, r(2) = 0.934).
      A new derivative, 4-oxo-4-(4-hydroxyindole)butanoic acid, was designed, taking
      into account the CoMSIA field and the binding mode derived by FlexX docking. This
      rationally designed compound exhibits an ALR2 inhibition with an IC(50) value of
      7.4 microM, which compares favorably to that of a well-known ALR2 inhibitor,
      tolrestat (IC(50) = 16 microM) and represents a potency approximately 240-fold
      higher than that of an original phenethylamine lead compound, YUA001.

PMID- 14667217
TI  - Investigation of neuraminidase-substrate recognition using molecular dynamics and
      free energy calculations.
AB  - Development of the new generation of therapeutics against the influenza viral
      coat protein neuraminidase is a response to the continuing threat of influenza
      epidemics. A variety of structurally similar compounds have been reported that
      vary greatly in their ability to inhibit neuraminidase, a critical enzyme that
      cleaves sialic acid and promotes virion release. To determine how neuraminidase
      exhibits this wide range of affinities with structurally similar compounds,
      molecular dynamic simulations, coupled with free energy calculations, were used
      to determine the binding components of a series of neuraminidase inhibitors.
      Using four cocrystal structures of neuraminidase-inhibitor complexes, we examined
      the structural and energetic components of ligand potency and selectivity. An in
      depth energetic analysis, including internal energy, entropy, and nonbonded
      interactions, reveals that potency of ligand binding is governed by nonpolar
      contacts. Electrostatic components generally oppose binding, although two of the
      best inhibitors use electrostatic interactions to orient the ligand. This
      investigation suggests that the enhanced selectivity and potency of the better
      ligands may arise from an improved positioning of their ligand atoms in the
      active site due to polar and hydrophobic functionalities. Simulations that
      included crystal water molecules in the active site indicate that the more potent
      ligands make less use of water-mediated interactions.

PMID- 14667218
TI  - Optimization of the pharmacophore model for 5-HT7R antagonism. Design and
      synthesis of new naphtholactam and naphthosultam derivatives.
AB  - We present in this study an optimization of a preliminary pharmacophore model for
      5-HT(7)R antagonism, with the incorporation of recently reported ligands and
      using an efficient procedure with the CATALYST program. The model consists of
      five features: a positive ionizable atom (PI), a H-bonding acceptor group (HBA),
      and three hydrophobic regions (HYD). This model has been supported by the design,
      synthesis, and biological evaluation of new naphtholactam and naphthosultam
      derivatives of general structure I (39-72). A systematic structure-affinity
      relationship (SAFIR) study on these analogues has allowed us to confirm that the
      model incorporates the essential structural features for 5-HT(7)R antagonism. In
      addition, computational simulation of the complex between compound 56 and a
      rhodopsin-based 3D model of the 5-HT(7)R transmembrane domain has permitted us to
      define the molecular details of the ligand-receptor interaction and gives
      additional support to the proposed pharmacophore model for 5-HT(7)R antagonism:
      (i) the HBA feature of the pharmacophore model binds Ser(5.42) and Thr(5.43),
      (ii) the HYD1 feature interacts with Phe(6.52), (iii) the PI feature forms an
      ionic interaction with Asp(3.32), and (iv) the HYD3 (AR) feature interacts with a
      set of aromatic residues (Phe(3.28), Tyr(7.43)). These results provide the tools
      for the design and synthesis of new ligands with predetermined affinities and
      pharmacological properties.

PMID- 14667219
TI  - Synthesis and structure-activity relationship of aminobenzophenones. A novel
      class of p38 MAP kinase inhibitors with high antiinflammatory activity.
AB  - We wish to report the synthesis and structure-activity relationship (SAR) of a
      series of 4-aminobenzophenones, as a novel compound class with high
      antiinflammatory activity. Our initial lead, (4-[(2
      aminophenyl)amino]phenyl)(phenyl)methanone (3), was systematically optimized and
      resulted in compounds that potently inhibited the release of the proinflammatory
      cytokines IL-1beta and TNF-alpha in human peripheral blood mononuclear cells
      stimulated by LPS. One of the most potent compounds, among others, was (4-[(2
      aminophenyl)amino]-2-chlorophenyl)(2-methylphenyl)methanone (45) with IC(50)
      values of 14 and 6 nM for the inhibition of IL-1beta and TNF-alpha, respectively.
      Furthermore, we found these types of compounds to be potent and selective p38 MAP
      kinase inhibitors, e.g. 45 had an IC(50) value of 10 nM. Molecular modeling was
      used to rationalize our SAR data and to propose a model for the interaction of
      compound 45 with the p38 MAP kinase. The model involved a favorable hydrogen bond
      between the carbonyl group of the benzophenone and the NH of Met-109, positioning
      ring A in the hydrophobic pocket I of the enzyme. Good antiinflammatory effects
      were demonstrated in two murine models of dermatitis after topical application
      (oxazolone and TPA model).

PMID- 14667220
TI  - Structure-based design, synthesis, and antimicrobial activity of indazole-derived
      SAH/MTA nucleosidase inhibitors.
AB  - The structure-based design, synthesis, and biological activity of a novel
      indazole-containing inhibitor series for S-adenosyl
      homocysteine/methylthioadenosine (SAH/MTA) nucleosidase are described. Use of 5
      aminoindazole as the core scaffold provided a structure-guided series of low
      nanomolar inhibitors with broad-spectrum antimicrobial activity. The
      implementation of structure-based methodologies provided a 6000-fold increase in
      potency over a short timeline (several months) and an economy of synthesized
      compounds.

PMID- 14667221
TI  - Shape signatures: a new approach to computer-aided ligand- and receptor-based
      drug design.
AB  - A unifying principle of rational drug design is the use of either shape
      similarity or complementarity to identify compounds expected to be active against
      a given target. Shape similarity is the underlying foundation of ligand-based
      methods, which seek compounds with structure similar to known actives, while
      shape complementarity is the basis of most receptor-based design, where the goal
      is to identify compounds complementary in shape to a given receptor. These
      approaches can be extended to include molecular descriptors in addition to shape,
      such as lipophilicity or electrostatic potential. Here we introduce a new
      technique, which we call shape signatures, for describing the shape of ligand
      molecules and of receptor sites. The method uses a technique akin to ray-tracing
      to explore the volume enclosed by a ligand molecule, or the volume exterior to
      the active site of a protein. Probability distributions are derived from the ray
      trace, and can be based solely on the geometry of the reflecting ray, or may
      include joint dependence on properties, such as the molecular electrostatic
      potential, computed over the surface. Our shape signatures are just these
      probability distributions, stored as histograms. They converge rapidly with the
      length of the ray-trace, are independent of molecular orientation, and can be
      compared quickly using simple metrics. Shape signatures can be used to test for
      both shape similarity between compounds and for shape complementarity between
      compounds and receptors and thus can be applied to problems in both ligand- and
      receptor-based molecular design. We present results for comparisons between small
      molecules of biological interest and the NCI Database using shape signatures
      under two different metrics. Our results show that the method can reliably
      extract compounds of shape (and polarity) similar to the query molecules. We also
      present initial results for a receptor-based strategy using shape signatures,
      with application to the design of new inhibitors predicted to be active against
      HIV protease.

PMID- 14667222
TI  - Analyses of activity for factor Xa inhibitors based on Monte Carlo simulations.
AB  - Monte Carlo/Extended Linear Response (MC/ELR) simulations have been conducted on
      60 inhibitors of human factor Xa to determine the important interactions
      associated with their activity. A variety of physicochemical descriptors were
      configurationally averaged during the course of the simulations of each inhibitor
      bound to factor Xa and free in water. A regression equation was then derived; it
      reproduces the experimental inhibition data with a correlation coefficient, r(2),
      of 0.74, an rms error of 0.67 kcal/mol, and an average unsigned error of 0.60
      kcal/mol using only two physically reasonable descriptors. The two factors that
      emerged as important in determining inhibitory potential are (1) favorable van
      der Waals interactions between protein and ligand and (2) direct hydrogen bonding
      between the inhibitor and protein. The conclusions were supported with structural
      analyses and results of MC/free energy perturbation (FEP) calculations.

PMID- 14667223
TI  - Computer modeling of selective regions in the active site of nitric oxide
      synthases: implication for the design of isoform-selective inhibitors.
AB  - Selective inhibition of nitric oxide synthase (NOS) isoforms has great
      therapeutic potential in the treatment of certain disease states arising from the
      pathological overproduction of nitric oxide. In this study three structures of
      each NOS isoform were employed to examine selective regions in the active site
      using the GRID/CPCA approach. In the GRID calculations, 10 probes covering
      hydrophobic, steric, and hydrogen-bond-acceptor and -donor interactions were used
      to calculate the molecular interaction fields (MIFs) in the active site. The side
      chain flexibility of the residues and the grid spacings were considered at the
      same time. Consensus principal component analysis (CPCA) was applied to analyze
      the MIFs differences in the active site between the NOS isoforms. By combining
      the cutout tool with GRID/CPCA pseudofield differential plots, several selective
      regions in the active site were identified. The selectivity analysis showed that
      the most important determinants for NOS inhibitor selectivity are hydrophobic and
      charge-charge interactions. Twenty-five inhibitors of NOS were then docked into
      the active site using the program AutoDock3.0. The regions identified as being
      important for selectivity by this method are in excellent agreement with
      inhibitor structure-activity relationships. A rational usage of the selective
      region described in this work should make it possible to develop NOS isoform
      selective inhibitors.

PMID- 14667225
TI  - Three-dimensional quantitative structure-activity relationship analyses of
      peptide substrates of the mammalian H+/peptide cotransporter PEPT1.
AB  - The utilization of the carrier protein PEPT1 for the absorption of peptidomimetic
      drug molecules is a promising strategy for oral drug administration and
      increasing bioavailability. In the absence of structural information on the
      binding mode of substrates to PEPT1, a computational study was conducted to
      explore the structural requirements for substrates and to derive a predictive
      model that may be used for the design of novel orally active drugs. A comparative
      molecular field analysis (CoMFA) and a comparative molecular similarity indices
      analysis (CoMSIA) were performed on a series of 79 dipeptide-type substrates for
      which affinity data had been collected in a single test system under the same
      conditions. These studies produced models with conventional r(2) and cross
      validated coefficient (q(2)) values of 0.901 and 0.642 for CoMFA and 0.913 and
      0.776 for CoMSIA. The models were validated by an external test set of 19
      dipeptides and dipeptide derivatives. CoMSIA contour maps were used to identify
      the recognition elements that are relevant for the binding of PEPT1 substrates.
      The 3D QSAR models provide an insight in the interactions between substrates and
      PEPT1 on the molecular level and allow the prediction of affinity constants of
      new compounds.

PMID- 14667224
TI  - Design, synthesis, and biological evaluation of indenoisoquinoline topoisomerase
      I inhibitors featuring polyamine side chains on the lactam nitrogen.
AB  - The indenoisoquinolines are a class of noncamptothecin topoisomerase I inhibitors
      that display significant cytotoxicity in human cancer cell cultures. They offer a
      number of potential advantages over the camptothecins, including greater chemical
      stability, formation of more persistent cleavage complexes, and induction of a
      unique pattern of DNA cleavage sites. Molecular modeling has suggested that
      substituents on the indenoisoquinoline lactam nitrogen would protrude out of the
      DNA duplex in the ternary cleavage complex through the major groove. This
      indicates that relatively large substituents in that location would be tolerated
      without compromising biological activity. As a strategy for increasing the
      potencies and potential therapeutic usefulness of the indenoisoquinolines, a
      series of compounds was synthesized containing polyamine side chains on the
      lactam nitrogen. The rationale for the synthesis of these compounds was that the
      positively charged ammonium cations would increase DNA affinity through
      electrostatic binding to the negatively charged DNA backbone, and the polyamines
      might also facilitate cellular uptake by utilization of polyamine transporters.
      The key step in the synthesis involved the condensation of Schiff bases,
      containing protected amine side chains, with substituted homophthalic anhydrides,
      to afford cis-3-aryl-4-carboxy-1-isoquinolones. These isoquinolones were then
      converted to indenoisoquinolines with thionyl chloride. Although monoamines were
      much more potent than the lead compound, no significant increase in potency was
      observed through incorporation of additional amino groups in the side chain.
      However, one of the monoamine analogues, which features a bis(2
      hydroxyethyl)amino group in the side chain, proved to be one of the most
      cytotoxic indenoisoquinoline synthesized to date, with a GI50 mean-graph midpoint
      (MGM) of 0.07 microM in the NIH human cancer cell culture screen, and
      topoisomerase I inhibitory activity comparable to that of camptothecin.

PMID- 14667226
TI  - Parallel solid-phase synthesis and evaluation of inhibitors of Streptomyces
      coelicolor type II dehydroquinase.
AB  - A series of 1-substituted and 4-substituted benzyl analogues of the known
      inhibitor (1S,3R,4R)-1,3,4-trihydroxy-5-cyclohexene-1-carboxylic acid has been
      synthesized and tested as inhibitors of Streptomyces coelicolor type II
      dehydroquinase. The solid-phase syntheses of 18 new analogues are reported. The
      most potent inhibitor, 2-nitrobenzyloxy analogue 5i, has K(i) of 8 microM, more
      than 30 times lower than the K(M) of the substrate and approximately 4 times more
      potent than the original inhibitor. The binding modes of the synthesized
      analogues in the active site were studied by molecular docking with GOLD 2.0.

PMID- 14667227
TI  - Synthesis and biological evaluation of 3-(4-substituted-phenyl)-N-hydroxy-2
      propenamides, a new class of histone deacetylase inhibitors.
AB  - Inhibitors of histone deacetylases (HDACs) have been shown to induce
      differentiation and/or apoptosis of human tumor cells. Novel 3-(4-substituted
      phenyl)-N-hydroxy-2-propenamides have been prepared as a new class of HDAC
      inhibitors and evaluated for their antiproliferative activity and HDAC inhibitory
      activity. Incorporation of a 1,4-phenylene carboxamide linker, shown by 5, and a
      4-(dimethylamino)phenyl or 4-(pyrrolidin-1-yl)phenyl group as a cap substructure
      generated highly potent hydroxamic acid-based HDAC inhibitors 5a and 5b.

PMID- 14667228
TI  - Synthesis and structure-activity relationship of mannose-based peptidomimetics
      selectively blocking integrin alpha4beta7 binding to mucosal addressin cell
      adhesion molecule-1.
AB  - As part of our ongoing research in the development of alpha4beta7 integrin
      antagonists, we are interested in peptidomimetics based on a rigid scaffold to
      allow the display of essential side chains in a suitable binding conformation
      while eliminating backbone amide bonds and therefore improving pharmacokinetic
      parameters of the drug. Except for a few examples, peptidomimetics scaffolds have
      only been moderately successful and often yield molecules that lack the potency
      of their peptide counterparts. However, we present herein a successful
      application of using a rigid scaffold. Starting from a mannopyranoside analogue
      previously discovered in our laboratory as an inhibitor of the
      alpha4beta1/vascular cell adhesion molecule interaction, a biased library of
      functionalized carbohydrates was developed. One compound emerged from this
      library as an active and selective antagonist toward the alpha4beta7/mucosal
      addressin cell adhesion molecule interaction. Conformational implications and the
      relevance of different pharmacophoric patterns will be discussed in order to
      explain the reverse selectivity and enhanced affinity.

PMID- 14667229
TI  - Synthesis and biological evaluation of iodinated and fluorinated 9-(2
      hydroxypropyl) and 9-(2-hydroxyethoxy)methyl purine nucleoside analogues.
AB  - The novel fluorinated and iodinated purine derivatives containing 9-(2
      hydroxypropyl) (1a-7a and 9a-13a) and 9-(2-hydroxyethoxymethyl) (1b-3b, 5b, and
      7b-12c) side chains were synthesized by a multistep synthetic route involving
      Baltz-Schiemann's fluorination and diazotation/iodination as key reactions. An
      unequivocal proof for the stereostructure of 5b was obtained by X-ray structure
      analysis. New compounds were evaluated for their cytostatic activity against
      murine leukemia (L1210); mammary carcinoma (FM3A); and human T-lymphocytes
      (Molt4/C8 and CEM), melanoma (HBL), cervical carcinoma (HeLa), colon carcinoma
      (HT29 and SW620), laryngeal carcinoma (Hep2), and pancreatic carcinoma (MiaPaCa2)
      as well as diploid fibroblasts (WI38). Of all the compounds, the 2-aminopurin-6
      thione derivative 9a showed the most pronounced inhibitory activity against human
      SW620 cells. The 2-aminopurin-6-thione derivative 9b exhibited the most selective
      inhibitory activity against human HeLa, Hep2, SW620, and murine L1210 cell
      proliferation as compared to normal fibroblast (WI38) cell proliferation. None of
      the compounds showed inhibitory activities against HIV-1, HIV-2, HSV-1, and HSV
      2, vaccinia, vesicular stomatitis, parainfluenza-3, reovirus-1, Sindbis,
      Coxsackie B4, or respiratory syncytial virus. The new purine derivatives, and
      particularly 9a and 9b, appear to demonstrate sufficient cytostatic potency and
      selectivity to justify further evaluation of their potential.

PMID- 14667230
TI  - Novel lavendamycin analogues as potent HIV-reverse transcriptase inhibitors:
      synthesis and evaluation of anti-reverse transcriptase activity of amide and
      ester analogues of lavendamycin.
AB  - Novel lavendamycins including two water soluble derivatives were synthesized via
      short and efficient methods. Pictet-Spengler condensation of 7-N-acylamino-2
      formylquinoline-5,8-diones with tryptophans produced lavendamycin esters or
      amides 11-17. Lavendamycins 18-21 were obtained, respectively, by further
      transformations of 13-15 and 17. Several lavendamycins were found to be potent
      HIV reverse transcriptase inhibitors with very low toxicity in vitro and in vivo.
      Several compounds also acted either additively or synergistically to inhibit
      enzyme activity together with AZT-triphosphate.

PMID- 14667231
TI  - Improving structure-based virtual screening by multivariate analysis of scoring
      data.
AB  - Three different multivariate statistical methods, PLS discriminant analysis, rule
      based methods, and Bayesian classification, have been applied to multidimensional
      scoring data from four different target proteins: estrogen receptor alpha
      (ERalpha), matrix metalloprotease 3 (MMP3), factor Xa (fXa), and acetylcholine
      esterase (AChE). The purpose was to build classifiers able to discriminate
      between active and inactive compounds, given a structure-based virtual screen.
      Seven different scoring functions were used to generate the scoring matrices. The
      classifiers were compared to classical consensus scoring and single scoring
      functions. The classifiers show a superior performance, with rule-based methods
      being most effective. The precision of correctly predicting an active compound is
      about 90% for three of the targets and about 25% for acetylcholine esterase. On
      the basis of these results, a new two-stage approach is suggested for structure
      based virtual screening where limited activity information is available.

PMID- 14667232
TI  - Bisintercalating threading diacridines: relationships between DNA binding,
      cytotoxicity, and cell cycle arrest.
AB  - We have synthesized a series of bis(9-aminoacridine-4-carboxamides) linked via
      the 9-position with neutral flexible alkyl chains, charged flexible polyamine
      chains, and a semirigid charged piperazine-containing chain. The carboxamide side
      chains comprise N,N-dimethylaminoethyl and ethylmorpholino groups. The compounds
      are designed to bisintercalate into DNA by a threading mode, in which the side
      chains are intended to form hydrogen-bonding contacts with the O6/N7 atoms of
      guanine in the major groove, and the linkers are intended to lie in the minor
      groove. By this means, we anticipate that they will dissociate slowly from DNA,
      and be cytotoxic as a consequence of template inhibition of transcription. The
      dimers remove and reverse the supercoiling of closed circular DNA with helix
      unwinding angles ranging from 26 degrees to 46 degrees, confirming bifunctional
      intercalation in all cases, and the DNA complexes of representative members
      dissociate many orders of magnitude more slowly than simple aminoacridines.
      Cytotoxicity for human leukemic CCRF-CEM cells was determined, the most active
      agents having IC(50) values of 35-50 nM in a range extending over 20-fold, with
      neither the dimethylaminoethyl nor the ethylmorpholino series being intrinsically
      more toxic. In common with established transcription inhibitors, the morpholino
      series, with one exception, have no effect on cell cycle distribution in randomly
      dividing CCRF-CEM populations. By contrast, the dimethylaminoethyl series, with
      two exceptions, cause G2/M arrest in the manner of topoisomerase poisons,
      consistent with possible involvement of topoisomerases in their mode of action.
      Thus, the cellular response to these bisintercalating threading agents is complex
      and appears to be determined by both their side chain and linker structures.
      There are no simple relationships between structure, cytotoxicity, and cell cycle
      arrest, and the origins of this complexity are unclear given that the compounds
      bind to DNA by a common mechanism.

PMID- 14667233
TI  - Generation of bis-cationic heterocyclic inhibitors of Bacillus subtilis HPr
      kinase/phosphatase from a ditopic dynamic combinatorial library.
AB  - Ditopic dynamic combinatorial libraries were generated and screened toward
      inhibition of the bifunctional enzyme HPr kinase/phosphatase from Bacillus
      subtilis. The libraries were composed of all possible combinations resulting from
      the dynamic interconversion of 16 hydrazides and five monoaldehyde or dialdehyde
      building blocks, resulting in libraries containing up to 440 different
      constituents. Of all possible acyl hydrazones formed, active compounds containing
      two terminal cationic heterocyclic recognition groups separated by a spacer of
      appropriate structure could be rapidly identified using a dynamic deconvolution
      procedure. Thus, parallel testing of sublibraries where one specific component
      was excluded basically revealed all the essential components. A potent ditopic
      inhibitor, based on 2-aminobenzimidazole, was identified from the process.

PMID- 14667234
TI  - Synthesis and pharmacological identification of neutral histamine H1-receptor
      antagonists.
AB  - In the present study we searched for neutral antagonists for the human histamine
      H(1)-receptor (H(1)R) by screening newly synthesized ligands that are
      structurally related to H(1)R agonists for their affinity using radioligand
      displacement studies and by assessing their functional activity via performing a
      NF-kappaB driven reporter-gene assay that allows for the detection of both
      agonistic and inverse agonistic responses. Starting from the endogenous agonist
      for the H(1)R, histamine, we synthesized and tested various analogues and
      ultimately identified several compounds with partial inverse agonistic properties
      and two neutral H(1)-receptor antagonists, namely 2-[2-(4,4-diphenylbutyl)-1H
      imidazol-4-yl]ethylamine (histabudifen, 18d) (pK(i) = 5.8, alpha = 0.02) and 2-[2
      (5,5-diphenylpentyl)-1H-imidazol-4-yl]ethylamine (histapendifen, 18e) (pK(i) =
      5.9, alpha = -0.09).

PMID- 14667235
TI  - Constrained derivatives of stylostatin 1. 1. Synthesis and biological evaluation
      as potential anticancer agents.
AB  - Hydroxyaminolactams have been used as constrained surrogates of the Ser-Leu
      dipeptide in the synthesis of analogues of the cycloheptapeptide stylostatin 1
      (2). The rate of cyclization through formation of the Ile-Pro amide bond allowed
      us to prove that the valerolactams used induced a turn in the linear precursor.
      Ring closure at the Pro-Phe amide bond was much quicker and provided access to
      larger amounts of the target structures, with high purity. The conformation of
      psi-stylostatin 4 was compared to that of native stylostatin 1 using NMR
      analysis. The ability of three psi-stylostatins and the native stylostatin 1 to
      inhibit growth of cancer cell lines was tested. None of the compounds showed
      activity below 1 microM. A possible relationship between the decrease in activity
      and the presence of the piperidone Ser-Leu surrogate is considered.

PMID- 14667236
TI  - 2-arylureidobenzoic acids: selective noncompetitive antagonists for the homomeric
      kainate receptor subtype GluR5.
AB  - A series of 2-arylureidobenzoic acids (AUBAs) was prepared by a short and
      effective synthesis, and the pharmacological activity at glutamate receptors was
      evaluated in vitro and in vivo. The compounds showed noncompetitive antagonistic
      activity at the kainate receptor subtype GluR5. The most potent compounds showed
      more than 50-fold selectivity for GluR5 compared to GluR6 and the AMPA receptor
      subtypes GluR1-4. The structure-activity relationships for the AUBAs showed
      distinct structural requirements for the substituents on the two aromatic ring
      systems. Only para-substituents were tolerated on the benzoic acid moiety (ring
      A), whereas ring B tolerated a variety of substituents, but with a preference for
      lipophilic substituents. The most potent compounds had a 4-chloro substituent on
      ring A and 3-chlorobenzene (6b), 2-naphthalene (8h), or 2-indole (8k) as ring B
      and had IC(50) values of 1.3, 1.2, and 1.2 microM, respectively, in a functional
      GluR5 assay. Compound 6c (IC(50) = 4.8 microM at GluR5) showed activity in the in
      vivo ATPA rigidity test, indicating that 6c has better pharmacokinetic properties
      than 8h, which was inactive in this test. The AUBAs are the first example of a
      series of noncompetitive GluR5-selective antagonists and may prove to be
      important pharmacological tools and leads in the search for therapeutic
      glutamatergic agents.

PMID- 14667238
TI  - Estimation of central aortic pressure by SphygmoCor requires accurate peripheral
      pressure measurement.

PMID- 14667239
TI  - Estimation of central aortic pressure: shedding new light or clouding the issue?

PMID- 14667241
TI  - Vision related quality of life and topical glaucoma treatment side effects.
AB  - BACKGROUND: Local tolerance of topical glaucoma treatment is important to achieve
      a good compliance. The aim of this study was to evaluate the consequences of
      local anti-glaucoma drug side effects on the vision-related quality of life
      (QoL). METHODS: A mail survey was sent to 20,000 homes of a panel representative
      of the French population asking whether one member of the family was suffering
      from ocular hypertension (OHT) or glaucoma. (POAG) A computer-assisted telephone
      interviewing system was used to confirm self-reported glaucoma, to describe the
      disease and its treatment, and medical item consumption. Vision-related QoL was
      assessed with the NEI-VFQ-25 (National Eye Institute Visual - Function
      Questionnaire) and local tolerance with the COMTOL (Comparison of Ophthalmic
      Medications for TOLerability). RESULTS: 13,352 homes (66.7%) answered the mail.
      581 people declared they were suffering from glaucoma or OHT. Prevalence was
      1.8%, increasing with age. 204 patients were selected at random Their NEI-VFQ-25
      global score showed an overall good QoL. Two domain scores showed some
      deterioration: general health and driving. 62.4% of the patients cited at least
      one local side effect. 25.4% had burning, 20.8% blurred vision and 20.2% tearing.
      Poor vision related QoL was associated with the presence of local side effects
      leading to poor perceived treatment satisfaction. Dissatisfied patients visited
      their ophthalmologist more frequently. CONCLUSION: Based on a representative
      French sample, poor vision related QoL was associated with topical drug side
      effects that also impact patient satisfaction and compliance. Longitudinal data
      collection should be performed to confirm our findings.

PMID- 14667242
TI  - Raised houses reduce mosquito bites.
AB  - BACKGROUND: In many parts of continental Africa house construction does not
      appear to impede entry of malaria vectors and, given their generally late biting
      cycle, the great majority of transmission takes place indoors. In contrast, many
      houses in Sao Tome, 140 km off the coast of Gabon, are raised on stilts and built
      of wooden planks. Building on stilts is a time-honoured, but largely untested,
      way of avoiding mosquito bites. Exposure may also be affected by mosquito
      activity times and age composition of host-seeking females. A study was therefore
      undertaken on the island of Sao Tome to determine if exposure to Anopheles
      gambiae, the only vector on the island, varied with house construction or time of
      the night. METHODS: A series of all-night landing collections were undertaken out
      of doors at ground level, inside houses at ground level, on the verandas of, and
      inside houses built on stilts. The gonotrophic age of an unselected sample of
      insects from the first three hours of landing collection (18:00-21:00) was
      determined by dissection. In addition, 1,149 miniature light-trap collections
      were obtained from 125 houses in the study area. Numbers collected were related
      to house construction. RESULTS: Biting of An. gambiae took place primarily
      outside at ground level. Less than one third of biting occurred inside houses.
      Houses built on stilts had half the number of An. gambiae in them compared to
      those built at ground level. Conversely houses with an eaves gap had more An.
      gambiae in them than houses without such a gap. Gonotrophic age did not affect
      house entry rates in An. gambiae. House construction affected Culex
      quinquefasciatus less than An. gambiae. Mean density per house, derived from a
      series of 1,490 randomly assigned light-trap collections, was over-dispersed with
      18% of houses having 70% of the vectors. CONCLUSION: House construction plays an
      important role in determining exposure to malaria vectors in Sao Tome. Neighbours
      can have very different exposure levels. Recommendations for improvement in
      control are given.

PMID- 14667243
TI  - Linking field-based ecological data with remotely sensed data using a geographic
      information system in two malaria endemic urban areas of Kenya.
AB  - BACKGROUND: Remote sensing technology provides detailed spectral and thermal
      images of the earth's surface from which surrogate ecological indicators of
      complex processes can be measured. METHODS: Remote sensing data were overlaid
      onto georeferenced entomological and human ecological data randomly sampled
      during April and May 2001 in the cities of Kisumu (population asymptotically
      equal to 320,000) and Malindi (population asymptotically equal to 81,000), Kenya.
      Grid cells of 270 meters x 270 meters were used to generate spatial sampling
      units for each city for the collection of entomological and human ecological
      field-based data. Multispectral Thermal Imager (MTI) satellite data in the
      visible spectrum at five meter resolution were acquired for Kisumu and Malindi
      during February and March 2001, respectively. The MTI data were fit and
      aggregated to the 270 meter x 270 meter grid cells used in field-based sampling
      using a geographic information system. The normalized difference vegetation index
      (NDVI) was calculated and scaled from MTI data for selected grid cells.
      Regression analysis was used to assess associations between NDVI values and
      entomological and human ecological variables at the grid cell level. RESULTS:
      Multivariate linear regression showed that as household density increased, mean
      grid cell NDVI decreased (global F-test = 9.81, df 3,72, P-value = <0.01;
      adjusted R2 = 0.26). Given household density, the number of potential anopheline
      larval habitats per grid cell also increased with increasing values of mean grid
      cell NDVI (global F-test = 14.29, df 3,36, P-value = <0.01; adjusted R2 = 0.51).
      CONCLUSIONS: NDVI values obtained from MTI data were successfully overlaid onto
      georeferenced entomological and human ecological data spatially sampled at a
      scale of 270 meters x 270 meters. Results demonstrate that NDVI at such a scale
      was sufficient to describe variations in entomological and human ecological
      parameters across both cities.

PMID- 14667244
TI  - Randomised prospective study for the effect of therapy on residual beta cell
      function in type-1 diabetes mellitus [ISRCTN70703138].
AB  - BACKGROUND: Newly diagnosed insulin-dependent diabetes mellitus is characterised
      by a temporary recovery of endogeneous insulin ("remission") after the beginning
      of medical treatment with subcutaneous insulin injections. Although most
      diabetologists think, that insulin reserve is related to reduced occurrence of
      diabetic long-term complications, such as eye, nerve and kidney disease, there is
      only one prospective controlled clinical study (the DCCT) addressing this
      question, however as secondary hypothesis. METHODS/DESIGN: Therefore, we composed
      a trial consisting of two cohorts with two therapeutic options within each cohort
      (conventional versus intensive therapy) and a three-year follow-up. In one group
      the patients are randomly assigned to the treatment regimes to test the
      statistical alternative hypothesis if variable insulin dosage is superior to
      fixed insulin injection in preserving insulin reserve measured by C-peptide in
      serum. Another group includes patients who prefer one of the two therapies,
      decline randomisation, but consent to follow-up. Apart from the determination of
      insulin reserve as a biological parameter a second primary endpoint was defined
      as 'therapeutic failure' according to the criteria of the European Association
      for the Study of Diabetes. Patients pass a training program to help them self
      manage diabetes. A standardised protocol is being set up to minimize centre
      effects and bias of health care providers. Potential patient dependent bias will
      be investigated by questionnaires measuring psychic coping processes of people
      with diabetes. Management of visit dates is directly navigated by the database.
      Automated visit-reminders are mailed to patients and caregivers to optimise the
      number of visits on schedule. Data quality is regularly monitored and centres are
      informed on the results of continuous data management.

PMID- 14667245
TI  - Wavelets filtering for classification of very noisy electron microscopic single
      particles images--application on structure determination of VP5-VP19C
      recombinant.
AB  - BACKGROUND: Images of frozen hydrated [vitrified] virus particles were taken
      close-to-focus in an electron microscope containing structural signals at high
      spatial frequencies. These images had very low contrast due to the high levels of
      noise present in the image. The low contrast made particle selection,
      classification and orientation determination very difficult. The final purpose of
      the classification is to improve the signal-to-noise ratio of the particle
      representing the class, which is usually the average. In this paper, the proposed
      method is based on wavelet filtering and multi-resolution processing for the
      classification and reconstruction of this very noisy data. A multivariate
      statistical analysis (MSA) is used for this classification. RESULTS: The MSA
      classification method is noise dependent. A set of 2600 projections from a 3D map
      of a herpes simplex virus--to which noise was added--was classified by MSA. The
      classification shows the power of wavelet filtering in enhancing the quality of
      class averages (used in 3D reconstruction) compared to Fourier band pass
      filtering. A 3D reconstruction of a recombinant virus (VP5-VP19C) is presented as
      an application of multi-resolution processing for classification and
      reconstruction. CONCLUSION: The wavelet filtering and multi-resolution processing
      method proposed in this paper offers a new way for processing very noisy images
      obtained from electron cryo-microscopes. The multi-resolution and filtering
      improves the speed and accuracy of classification, which is vital for the 3D
      reconstruction of biological objects. The VP5-VP19C recombinant virus
      reconstruction presented here is an example, which demonstrates the power of this
      method. Without this processing, it is not possible to get the correct 3D map of
      this virus.

PMID- 14667246
TI  - Delayed leukocytosis after hard strength and endurance exercise: aspects of
      regulatory mechanisms.
AB  - BACKGROUND: During infections, polymorphonuclear neutrophilic granulocytes (PMN)
      are mobilized from their bone marrow stores, travel with blood to the affected
      tissue, and kill invading microbes there. The signal(s) from the inflammatory
      site to the marrow are unknown, even though a number of humoral factors that can
      mobilize PMN, are well known. We have employed a standardized, non-infectious
      human model to elucidate relevant PMN mobilizers. Well-trained athletes performed
      a 60-min strenuous strength workout of leg muscles. Blood samples were drawn
      before, during and just after exercise, and then repeatedly during the following
      day. Cortisol, GH, ACTH, complement factors, high-sensitive CRP (muCRP), IL-6, G
      CSF, IL-8 (CXCL8) and MIP-1beta (CCL4) were measured in blood samples. PMN
      chemotaxins in test plasma was assessed with a micropore membrane technique.
      RESULTS: About 5 hr after the workout, blood granulocytosis peaked to about 150%
      of baseline. Plasma levels of GH increased significantly 30 min into and 5 min
      after the exercise, but no increase was recorded for the other hormones. No
      significant correlation was found between concentrations of stress hormones and
      the subjects' later occurring PMN increases above their individual baselines.
      Plasma G-CSF increased significantly - but within the normal range - 65 min after
      the workout. IL-6 increased very slightly within the normal range, and the
      chemokines IL-8 and MIP-1beta did not increase consistently. However, we found a
      significant increase of hitherto non-identified PMN-chemotactic activity in
      plasma 35, 50, and 60 min after the exercise. No systemic complement activation
      was detected, and (mu)CRP was within the reference range at rest, 5 h and 23 h
      after the exercise. After endurance exercise, similar findings were made, except
      for a cortisol response, especially from non-elite runners. CONCLUSION:
      Apparently, a multitude of humoral factors can - directly or indirectly -
      mobilize PMN from marrow to blood; some of the factors are, others are not known
      to be, chemotactic. Under different conditions, different selections of these
      mobilizers may be used. In the late granulocytosis after heavy, long-lasting
      exercise a number of factors thought capable of mimicking the granulocytosis of
      infectious diseases were apparently irrelevant.

PMID- 14667247
TI  - Clasp knife in the gut: a case report.
AB  - BACKGROUND: A wide range of foreign bodies has been retrieved from the gut and
      reported. The presentation may be in the form of complications like intestinal
      obstruction, perforation and formation of abscesses etc but there is no case
      report of a half open clasp knife being retrieved from the ileum, the patient
      having thrived, in spite of its presence for a period of eight months. CASE
      PRESENTATION: A 30-year-old administrative clerk had undergone emergency
      abdominal surgery eight months previously under mysterious circumstances at a
      remote district hospital and had recovered completely. Later the blade of a knife
      was accidentally detected when an X ray of the abdomen was done during a routine
      follow-up visit to his family physician. Surgery revealed a clasp knife in the
      ileum, which was retrieved. The presence of an entero-enteric fistula short
      circuiting the loop was the secret of his earlier survival. CONCLUSIONS: To the
      best of our information this is the first case-report of a clasp knife in the gut
      and of the patient thriving in spite of its presence. We report here the dramatic
      sequence of events.

PMID- 14667248
TI  - The creation of new rotation arc to the rat latissimus dorsi musculo-cutaneous
      flap with delay procedures.
AB  - BACKGROUND: Latissimus dorsi musculocutaneous flap is one of the most frequently
      performed reconstructive techniques in surgery. Latissimus dorsi muscle has two
      arcs of rotation. It is classified as type V muscle. This muscle can be elevated
      on the thoracodorsal artery to cover large defects in the anterior chest and
      also, the muscle can be elevated on the segmental vessels to cover midline
      defects posteriorly. The aim of this study was to create a new arc of rotation on
      a vertical axis for the muscle and investigate effectiveness of vascular and
      chemical delays on the latissimus dorsi muscle flap with an inferior pedicle in
      an experimental rat model. We hypothesized that the latissimus dorsi muscle would
      be based on inferior pedicle by delay procedures. METHODS: We tested two
      different types of delay: vascular and combination of vascular and chemical. We
      also tried to determine how many days of "delay" can elicit beneficial effects of
      vascular and combination delays in an inferior pedicled latissimus dorsi
      musculocutaneous flap. To accomplish this, 48 male Sprague-Dawley rats were
      randomly subjected to vascular or combination delay (vascular and chemical). In
      addition, one ear of each rat was assigned into a delay procedure and the other
      ear was used as a control. Results were evaluated macroscopically, and micro
      angiography and histological examinations were also performed. As a result, there
      was a significant difference in viable flap areas between vascular delay alone
      and control groups (p < 0.05). RESULTS: The higher rate of flap viability was
      obtained in seven-day vascular delay alone. However, there was no significant
      difference in the viability between seven-day vascular delay and five-day
      vascular delay (p < 0.05), so the earliest time when the flap viability could be
      obtained was at five days. The rate of flap viability was significantly higher in
      the vascular delay combined with chemical delay than the control group (p <
      0.05). CONCLUSION: The combination of vascular and chemical delays increased the
      rate of viability. Nevertheless, there was no significant difference between
      vascular delay alone and combination of vascular and chemical delays. Chemical
      delay did not significantly decrease the delay period. Better histological and
      microangiographical results were achieved in delay groups compared to control
      groups. We concluded that the arch of the latissimus dorsi musculocutaneous flap
      can be changed and the flap can be used for various purposes with the delay
      procedures.

PMID- 14667249
TI  - The Greek translation of the symptoms rating scale for depression and anxiety:
      preliminary results of the validation study.
AB  - BACKGROUND: The aim of the current study was to assess the reliability, validity
      and the psychometric properties of the Greek translation of the Symptoms Rating
      Scale For Depression and Anxiety. The scale consists of 42 items and permits the
      calculation of the scores of the Beck Depression Inventory (BDI)-21, the BDI 13,
      the Melancholia Subscale, the Asthenia Subscale, the Anxiety Subscale and the
      Mania Subscale METHODS: 29 depressed patients 30.48 +/- 9.83 years old, and 120
      normal controls 27.45 +/- 10.85 years old entered the study. In 20 of them (8
      patients and 12 controls) the instrument was re-applied 1-2 days later.
      Translation and Back Translation was made. Clinical Diagnosis was reached by
      consensus of two examiners with the use of the SCAN v.2.0 and the IPDE. CES-D and
      ZDRS were used for cross-validation purposes. The Statistical Analysis included
      ANOVA, the Spearman Correlation Coefficient, Principal Components Analysis and
      the calculation of Cronbach's alpha. RESULTS: The optimal cut-off points were:
      BDI-21: 14/15, BDI-13: 7/8, Melancholia: 8/9, Asthenia: 9/10, Anxiety: 10/11.
      Chronbach's alpha ranged between 0.86 and 0.92 for individual scales. Only the
      Mania subscale had very low alpha (0.12). The test-retest reliability was
      excellent for all scales with Spearman's Rho between 0.79 and 0.91. CONCLUSIONS:
      The Greek translation of the SRSDA and the scales that consist it are both
      reliable and valid and are suitable for clinical and research use with
      satisfactory properties. Their properties are close to those reported in the
      international literature. However one should always have in mind the limitations
      inherent in the use of self-report scales.

PMID- 14667250
TI  - Fusion to GFP blocks intercellular trafficking of the sucrose transporter SUT1
      leading to accumulation in companion cells.
AB  - BACKGROUND: Plant phloem consists of an interdependent cell pair, the sieve
      element/companion cell complex. Sucrose transporters are localized to enucleate
      sieve elements (SE), despite being transcribed in companion cells (CC). Due to
      the high turnover of SUT1, sucrose transporter mRNA or protein must traffic from
      CC to SE via the plasmodesmata. Localization of SUT mRNA at plasmodesmatal
      orifices connecting CC and SE suggests RNA transport, potentially mediated by RNA
      binding proteins. In many organisms, polar RNA transport is mediated through RNA
      binding proteins interacting with the 3'-UTR and controlling localized protein
      synthesis. To study mechanisms for trafficking of SUT1, GFP-fusions with and
      without 3'-UTR were expressed in transgenic plants. RESULTS: In contrast to
      plants expressing GFP from the strong SUC2 promoter, in RolC-controlled
      expression GFP is retained in companion cells. The 3'-UTR of SUT1 affected
      intracellular distribution of GFP but was insufficient for trafficking of SUT1,
      GFP or their fusions to SEs. Fusion of GFP to SUT1 did however lead to
      accumulation of SUT1-GFP in the CC, indicating that trafficking was blocked while
      translational inhibition of SUT1 mRNA was released in CCs. CONCLUSION: A fusion
      with GFP prevents targeting of the sucrose transporter SUT1 to the SE while
      leading to accumulation in the CC. The 3'-UTR of SUT1 is insufficient for
      mobilization of either the fusion or GFP alone. It is conceivable that SUT1-GFP
      protein transport through PD to SE was blocked due to the presence of GFP,
      resulting in retention in CC particles. Alternatively, SUT1 mRNA transport
      through the PD could have been blocked due to insertion of GFP between the SUT1
      coding sequence and 3'-UTR.

PMID- 14667251
TI  - Relationship between gene co-expression and probe localization on microarray
      slides.
AB  - BACKGROUND: Microarray technology allows simultaneous measurement of thousands of
      genes in a single experiment. This is a potentially useful tool for evaluating co
      expression of genes and extraction of useful functional and chromosomal
      structural information about genes. RESULTS: In this work we studied the
      association between the co-expression of genes, their location on the chromosome
      and their location on the microarray slides by analyzing a number of eukaryotic
      expression datasets, derived from the S. cerevisiae, C. elegans, and D.
      melanogaster. We find that in several different yeast microarray experiments the
      distribution of the number of gene pairs with correlated expression profiles as a
      function of chromosomal spacing is peaked at short separations and has two
      superimposed periodicities. The longer periodicity has a spacing of 22 genes
      (approximately 42 Kb), and the shorter periodicity is 2 genes (approximately 4
      Kb). CONCLUSION: The relative positioning of DNA probes on microarray slides and
      source plates introduces subtle but significant correlations between pairs of
      genes. Careful consideration of this spatial artifact is important for analysis
      of microarray expression data. It is particularly relevant to recent microarray
      analyses that suggest that co-expressed genes cluster along chromosomes or are
      spaced by multiples of a fixed number of genes along the chromosome.

PMID- 14667252
TI  - Phylogenomic identification of five new human homologs of the DNA repair enzyme
      AlkB.
AB  - BACKGROUND: Combination of biochemical and bioinformatic analyses led to the
      discovery of oxidative demethylation - a novel DNA repair mechanism catalyzed by
      the Escherichia coli AlkB protein and its two human homologs, hABH2 and hABH3.
      This discovery was based on the prediction made by Aravind and Koonin that AlkB
      is a member of the 2OG-Fe2+ oxygenase superfamily. RESULTS: In this article, we
      report identification and sequence analysis of five human members of the (2OG
      Fe2+) oxygenase superfamily designated here as hABH4 through hABH8. These
      experimentally uncharacterized and poorly annotated genes were not associated
      with the AlkB family in any database, but are predicted here to be
      phylogenetically and functionally related to the AlkB family (and specifically to
      the lineage that groups together hABH2 and hABH3) rather than to any other
      oxygenase family. Our analysis reveals the history of ABH gene duplications in
      the evolution of vertebrate genomes. CONCLUSIONS: We hypothesize that hABH 4-8
      could either be back-up enzymes for hABH1-3 or may code for novel DNA or RNA
      repair activities. For example, enzymes that can dealkylate N3-methylpurines or
      N7-methylpurines in DNA have not been described. Our analysis will guide
      experimental confirmation of these novel human putative DNA repair enzymes.

PMID- 14667253
TI  - Evolution of phage with chemically ambiguous proteomes.
AB  - BACKGROUND: The widespread introduction of amino acid substitutions into
      organismal proteomes has occurred during natural evolution, but has been
      difficult to achieve by directed evolution. The adaptation of the translation
      apparatus represents one barrier, but the multiple mutations that may be required
      throughout a proteome in order to accommodate an alternative amino acid or
      analogue is an even more daunting problem. The evolution of a small bacteriophage
      proteome to accommodate an unnatural amino acid analogue can provide insights
      into the number and type of substitutions that individual proteins will require
      to retain functionality. RESULTS: The bacteriophage Qbeta initially grows poorly
      in the presence of the amino acid analogue 6-fluorotryptophan. After 25 serial
      passages, the fitness of the phage on the analogue was substantially increased;
      there was no loss of fitness when the evolved phage were passaged in the presence
      of tryptophan. Seven mutations were fixed throughout the phage in two independent
      lines of descent. None of the mutations changed a tryptophan residue.
      CONCLUSIONS: A relatively small number of mutations allowed an unnatural amino
      acid to be functionally incorporated into a highly interdependent set of
      proteins. These results support the 'ambiguous intermediate' hypothesis for the
      emergence of divergent genetic codes, in which the adoption of a new genetic code
      is preceded by the evolution of proteins that can simultaneously accommodate more
      than one amino acid at a given codon. It may now be possible to direct the
      evolution of organisms with novel genetic codes using methods that promote
      ambiguous intermediates.

PMID- 14667254
TI  - Statistical significance for hierarchical clustering in genetic association and
      microarray expression studies.
AB  - BACKGROUND: With the increasing amount of data generated in molecular genetics
      laboratories, it is often difficult to make sense of results because of the vast
      number of different outcomes or variables studied. Examples include expression
      levels for large numbers of genes and haplotypes at large numbers of loci. It is
      then natural to group observations into smaller numbers of classes that allow for
      an easier overview and interpretation of the data. This grouping is often carried
      out in multiple steps with the aid of hierarchical cluster analysis, each step
      leading to a smaller number of classes by combining similar observations or
      classes. At each step, either implicitly or explicitly, researchers tend to
      interpret results and eventually focus on that set of classes providing the
      "best" (most significant) result. While this approach makes sense, the overall
      statistical significance of the experiment must include the clustering process,
      which modifies the grouping structure of the data and often removes variation.
      RESULTS: For hierarchically clustered data, we propose considering the strongest
      result or, equivalently, the smallest p-value as the experiment-wise statistic of
      interest and evaluating its significance level for a global assessment of
      statistical significance. We apply our approach to datasets from haplotype
      association and microarray expression studies where hierarchical clustering has
      been used. CONCLUSION: In all of the cases we examine, we find that relying on
      one set of classes in the course of clustering leads to significance levels that
      are too small when compared with the significance level associated with an
      overall statistic that incorporates the process of clustering. In other words,
      relying on one step of clustering may furnish a formally significant result while
      the overall experiment is not significant.

PMID- 14667255
TI  - PubMatrix: a tool for multiplex literature mining.
AB  - BACKGROUND: Molecular experiments using multiplex strategies such as cDNA
      microarrays or proteomic approaches generate large datasets requiring biological
      interpretation. Text based data mining tools have recently been developed to
      query large biological datasets of this type of data. PubMatrix is a web-based
      tool that allows simple text based mining of the NCBI literature search service
      PubMed using any two lists of keywords terms, resulting in a frequency matrix of
      term co-occurrence. RESULTS: For example, a simple term selection procedure
      allows automatic pair-wise comparisons of approximately 1-100 search terms versus
      approximately 1-10 modifier terms, resulting in up to 1,000 pair wise
      comparisons. The matrix table of pair-wise comparisons can then be surveyed,
      queried individually, and archived. Lists of keywords can include any terms
      currently capable of being searched in PubMed. In the context of cDNA microarray
      studies, this may be used for the annotation of gene lists from clusters of genes
      that are expressed coordinately. An associated PubMatrix public archive provides
      previous searches using common useful lists of keyword terms. CONCLUSIONS: In
      this way, lists of terms, such as gene names, or functional assignments can be
      assigned genetic, biological, or clinical relevance in a rapid flexible
      systematic fashion. http://pubmatrix.grc.nia.nih.gov/

PMID- 14667256
TI  - Acute myocardial infarction from spontaneous coronary artery dissection a case
      report and review of the literature.
AB  - Spontaneous coronary artery dissection is a rare event as a cause of acute
      myocardial infarction. Optimal treatment remains unclear. In this report, we
      describe a case of spontaneous acute coronary artery dissection presenting as
      recurrent acute myocardial infarction in a postmenopausal woman, successfully
      treated with systemic thrombolysis. The case is discussed with review of the
      pertinent literature.

PMID- 14667257
TI  - An unusual cause of dyspnea.
AB  - The case of a 71-year-old woman who presented with dyspnea and palpitations is
      presented. Workup yielded a diagnosis of Fabry's disease, and the patient was
      referred for therapy. Fabry's disease is a disorder of glycosphingolipid
      metabolism and has forms that are limited to the myocardium. There is evidence
      that it has been underrecognized as a cause of cardiac hypertrophy. Because
      screening can be done with a simple blood test and new treatment options appear
      promising, we recommend consideration of Fabry's disease in the workup of
      patients with cardiac hypertrophy.

PMID- 14667258
TI  - A new treatment modality in heart failure enhanced external counterpulsation
      (EECP).
AB  - Heart failure remains a significant health problem in the United States and in
      the world. Despite a surfeit of recent diagnostic and therapeutic advances,
      patients with heart failure remain inadequately helped. The overwhelming need for
      new and better therapies continues to stimulate scientists to investigate new
      technologies. Over the past several years the use of enhanced external
      counterpulsation as a treatment for chronic angina has steadily increased.
      Recently, its potential role in heart failure management has been shown. We
      review the role of enhanced external counterpulsation in heart failure management
      as an emerging noninvasive outpatient therapy.

PMID- 14667259
TI  - Cardiac troponin levels in heart failure.
AB  - Congestive heart failure (CHF) is a major cardiovascular disorder that is
      increasing in incidence, prevalence, and lethality. The prognostic significance
      of cardiac troponin levels among symptomatic and asymptomatic CHF has attracted
      recent interest. We sought to assess the significance of cardiac troponins in
      heart failure. These cardiac markers are associated with decreased left
      ventricular ejection fraction and poor prognosis in patients with CHF and are
      related to the severity of heart failure. The mechanism for the release of these
      markers seems to be from ventricular remodeling, ongoing myocyte degeneration,
      the presence of coronary artery disease, and reduced coronary reserve. In
      addition to B-type (brain) natriuretic peptide (BNP), cardiac troponin levels
      measured in patients admitted to the hospital could help risk-stratify patients
      and manage them effectively. BNP and cardiac troponins are easy to measure and
      can be repeated many times to follow patients, without interobserver variability.
      Theoretically, BNP is a marker of heart failure status and cardiac troponin is a
      marker of myocyte injury. The first therapeutic goal could be relief of
      circulatory congestion and lowering of BNP. The second goal could be attenuation
      of myocyte injury and lowering of cardiac troponins. Measuring and monitoring the
      levels of both could be highly effective means to reliably stratify the patients
      into low-, intermediate-, and high-risk groups for cardiac events and progression
      of heart failure. Furthermore, large-scale trials are necessary to establish them
      as noninvasive monitoring markers of heart failure and effectiveness of
      treatment.

PMID- 14667260
TI  - Heat shock proteins in cardiovascular disease a new therapeutic target.
AB  - Cells have the capability of defending themselves from various stressors by
      activating a genetic program with the production of substances known as heat
      shock proteins and their regulatory partners, the heat shock transcription
      factors. In this article, heat shock proteins are discussed, including their
      roles in pathophysiology and as possible pharmacologic targets to treat disease.
      Multiple investigations have demonstrated an elevation in heat shock proteins in
      patients with systemic hypertension, coronary artery disease, carotid
      atherosclerosis, and myocardial infarction and ischemia. As we further understand
      how to manipulate their expression, we can explore pharmacologic interventions
      and gene transfection techniques that can safely be used in humans.

PMID- 14667261
TI  - Spontaneous conversion of atrial fibrillation in the setting of biventricular
      pacing.

PMID- 14667262
TI  - A rare noncardiac cause for acute myocardial infarction in a 13-year-old patient.
AB  - A case of ST-segment elevation myocardial infarction in an adolescent patient is
      presented. The patient presented with resting angina and echocardiographic
      evidence of wall motion abnormalities in the inferior and posterior segments. The
      patient was known to have metastatic hepatocellular carcinoma. Tumor was seen in
      the left inferior pulmonary vein and is proposed to be the source of embolism
      causing myocardial infarction. Secondary to intracranial metastatic lesions, the
      patient was treated conservatively with opiates, nitrates, and beta-blockers.
      This case is an opportunity to review the causes and management of myocardial
      infraction in pediatric patients and represents a rare cause of embolic
      myocardial infraction.

PMID- 14667263
TI  - Drug-eluting stents. A review of the current literature.
AB  - Coronary interventions have revolutionized the treatment of coronary artery
      disease (CAD). Stents, which were used initially for the complications arising
      from coronary angiography gradually, came to occupy a more prominent role in
      coronary interventions. However, restenosis remained a limiting factor from a
      therapeutic point of view. Recent development of drug-eluting stents is a step
      toward overcoming this problem. This development has elicited a great interest in
      both physician as well as patient communities. We have reviewed the available
      medical evidence regarding drug-eluting stents.

PMID- 14667264
TI  - Glucocorticoid-remediable aldosteronism.
AB  - Glucocorticoid remediable aldosteronism (GRA) appears to be the most common
      monogenic form of human hypertension. As a result of chimeric gene duplication,
      aldosterone is ectopically synthesized in the zona fasciculata of the adrenal
      gland under the control of adrenocorticotropin (ACTH). Affected individuals are
      typically hypertensive, often with onset in youth, and demonstrate refractoriness
      to standard antihypertensives such as angiotensin-converting enzyme inhibitors
      and beta-blockers. GRA subjects are normokalemic but often develop hypokalemia
      when treated with a potassium-wasting diuretic. Analysis of affected kindreds has
      demonstrated a high prevalence of early cerebral hemorrhage, largely as a result
      of aneurysms. Identification of affected individuals should allow direct
      neurovascular screening and targeted antihypertensive therapy.

PMID- 14667265
TI  - AIDS associated with severe cor pulmonale and large pericardial effusion with
      cardiac tamponade.
AB  - Cardiac involvement in patients with advanced HIV/AIDS is common, including
      pericardial effusion and pulmonary hypertension. Although there is an increased
      incidence of pericardial effusion in patients with AIDS, most are small and
      asymptomatic. The presence of a pericardial effusion and/or pulmonary
      hypertension is associated with shortened survival. We present a case of a 43
      year-old man with AIDS and advanced cardiovascular involvement who developed
      severe cor pulmonale and a large pericardial effusion with cardiac tamponade.

PMID- 14667266
TI  - Transient atrioventricular block associated with intracranial hemorrhage.
AB  - Electrocardiographic changes and/or cardiac arrhythmias can be demonstrated in a
      majority of patients with intracranial hemorrhage. We present a rare case who
      developed intracranial hemorrhage associated with transient high-degree advanced
      atrioventricular block.

PMID- 14667267
TI  - Myocardial ischemia and congestive heart failure from a left main to coronary
      sinus fistula.
AB  - A coronary artery fistula (CAF) is a rare congenital anomaly first reported by
      Krause in 1865. It is defined as a direct communication between the coronary
      artery and any surrounding cardiac chamber or vascular structure, which bypasses
      the myocardial capillary bed. The incidence of small CAFs in an adult population,
      undergoing cardiac catheterization at the Cleveland Clinic, was 0.13%. In the
      same series, the incidence of large or multiple fistulas was less than that of
      small fistulas and was present in 0.05% of all patients screened. The natural
      history of CAF in adults remains undefined, as does the best approach to managing
      these patients with recommendations for early closure as well as conservative
      management found in the medical literature. We present a patient initially
      diagnosed with a clinically silent CAF who presents 10 years later with symptoms
      and many of the classic findings of a CAF. An alternative model for the
      management of CAF in adults is discussed.

PMID- 14667268
TI  - Clinical lung cancer indexed in Index Medicus and Medline.

PMID- 14667269
TI  - Highlights from the 10th World Conference on Lung Cancer. Vancouver, British
      Columbia, Canada, August 10-14, 2003.

PMID- 14667270
TI  - Granulocyte-macrophage colony-stimulating factor gene-transfected autologous
      tumor cell vaccine: focus[correction to fcous] on non-small-cell lung cancer.
AB  - Traditionally, non-small-cell lung cancer (NSCLC) is not thought of as an
      immunosensitive malignancy. However, recent clinical results with GVAX, a
      granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced
      autologous tumor vaccine, may suggest otherwise. This review summarizes immune
      induced activity caused by GM-CSF protein and GM-CSF gene-transfected vaccines.
      Initial indication of use for GM-CSF protein (sargramostim) was to improve
      neutrophil recovery following cytotoxic chemotherapy. However, several trials
      involving patients with hematologic malignancy demonstrated improvement in
      survival related to delayed disease progression in patients receiving
      sargramostim in combination with chemotherapy. Subsequently, others explored
      potential antitumor activity with sargramostim in a variety of trials. Results
      did not consistently demonstrate sufficient antitumor activity to justify routine
      use of sargramostim as an anticancer agent. Preclinical work with GM-CSF gene
      transfected vaccines, however, did demonstrate significant activity, thereby
      justifying clinical investigation. Patients with metastatic NSCLC who had
      previously failed chemotherapy demonstrated response to GVAX (3 of 33 complete
      responses) and dose-related improvement in survival (471 days vs. 174 days).

PMID- 14667271
TI  - Cell cycle modulators for the treatment of lung malignancies.
AB  - It has become clear in the past decade that most human malignancies, including
      lung neoplasms, have aberrations in cell cycle control. The tumor suppressor gene
      retinoblastoma is an important player in the G1/S transition and its function is
      abnormal in most human neoplasms. Retinoblastoma function is lost as a result of
      phosphorylation by the cyclin-dependent kinases (CDKs). Thus, modulation of CDKs
      may have an important use for the therapy and prevention of human neoplasms.
      Direct CDK modulators are small molecules that target specifically the adenosine
      triphosphate binding site of CDKs. In contrast, indirect CDK modulators affect
      CDK function by modulation of upstream pathways required for CDK activation. The
      first example of a direct small-molecule CDK modulator tested in the clinic,
      flavopiridol, is a pan-CDK inhibitor that not only promotes cell cycle arrest but
      also halts transcriptional elongation, promotes apoptosis, induces
      differentiation, and has antiangiogenic properties. The second example of direct
      small-molecule CDK modulators tested in clinical trials is UCN-01 (7
      hydroxystaurosporine). UCN-01 has interesting preclinical features: it inhibits
      Ca2+-dependent protein kinase C, promotes apoptosis, arrests cell cycle
      progression at G1/S, and abrogates checkpoints upon DNA damage. In summary, novel
      small-molecule CDK modulators are being tested in the clinic with interesting
      results. Although these small molecules are directed toward a very prevalent
      cause of carcinogenesis, their role in the clinical armamentarium is still
      uncertain.

PMID- 14667272
TI  - Management of advanced non-small-cell lung cancer in elderly populations.
AB  - Elderly patients, defined as those >or= 70 years of age, represent approximately
      40% of all patients diagnosed with non-small-cell lung cancer in the United
      States. Nonetheless, elderly patients have been underrepresented in national
      cooperative group trials, and many do not receive appropriate treatment. Whereas
      the benefit of systemic chemotherapy in younger patients is accepted by most
      clinicians, there remains a great deal of skepticism with respect to older
      patients, who are often labeled unfit for chemotherapy. More recent studies with
      a special focus on elderly patients demonstrate that these patients indeed
      benefit from chemotherapy. The landmark Elderly Lung Cancer Vinorelbine Italian
      Study Group trial and the Multicentre Italian Lung Cancer in the Elderly Study
      clarified the role of vinorelbine in the treatment of elderly patients.
      Retrospective and prospective subgroup analyses from selected North American
      trials suggested that elderly patients also benefit from platinum-based
      combinations. Whether elderly patients should be treated with single-agent versus
      combination chemotherapy is discussed in this review. The available data suggest
      that patients should be evaluated for chemotherapy based on their performance
      status and comorbidities rather than age alone. For elderly patients judged fit
      to receive combination chemotherapy, carboplatin-based regimens are a reasonable
      option. In elderly patients with less than optimal performance status or
      significant comorbid conditions, single-agent therapy may be more appropriate.

PMID- 14667273
TI  - Phase II study of an alternate carboplatin and gemcitabine dosing schedule in
      advanced non-small-cell lung cancer.
AB  - We conducted a phase II single-institution trial in a homogenous patient
      population with advanced non-small-cell lung cancer to determine whether changing
      the carboplatin schedule in the carboplatin/gemcitabine doublet would enhance
      tolerability and/or results. Thirty patients with stage IIIB (with malignant
      effusion) or stage IV disease received gemcitabine 1100 mg/m2, days 1 and 8 plus
      carboplatin at an area under the curve of 5 on day 8. Cycles were repeated every
      28 days, up to 6 cycles. A response rate of 10% was demonstrated (none complete),
      but an additional 45% of patients had stable disease. The median time to
      progression was 5.8 months and the median survival was 8.3 months. A 1-year
      survival rate of 27% and a 2-year survival rate of 16% were seen. The main
      nonhematologic toxicity was non-neutropenic infection. Thrombocytopenia occurred
      in 8 patients (27%; 7 grade 3, 1 grade 4). Carboplatin/gemcitabine with a day 8
      administration of carboplatin is well tolerated with a similar survival to
      established platinum-based doublets.

PMID- 14667274
TI  - Molecular pathogenesis of malignant mesothelioma and its relationship to simian
      virus 40.
AB  - Malignant mesothelioma is a relatively rare tumor, but the incidence of the
      disease appears to be increasing. Unique molecular changes are associated with
      the disease that distinguish it from lung cancers. Smoking is not an etiologic
      factor; the major causative agent is asbestos exposure, usually many years or
      decades before the development of the tumor. Recently, a simian virus, SV40, has
      been associated with malignant mesotheliomas and is a probable cofactor in tumor
      development. The molecular changes caused by each of these major etiologic
      factors and their interrelationships are the focus of this review.

PMID- 14667275
TI  - Antitumor activity and tolerability of gefitinib in patients with non-small-cell
      lung cancer treated in an expanded access program.
AB  - We present a series of cases that illustrate potential benefits of the targeted
      agent gefitinib for patients with advanced and heavily pretreated non-small-cell
      lung cancer (NSCLC). In 2 phase II clinical trials, 250 mg/day of gefitinib
      produced objective tumor response rates of 18% and 11%, with excellent tolerance
      in patients with advanced NSCLC who had previously received standard
      chemotherapy. Treatment with gefitinib also led to improvements in disease
      related symptoms in approximately 40% of cases. Gefitinib is one of a class of
      agents that selectively inhibit the epidermal growth factor receptor-tyrosine
      kinase, which is aberrantly activated in many human solid tumors. Gefitinib
      treatment resulted in objective radiographic regressions of tumor and symptom
      improvement in patients with advanced, heavily pretreated NSCLC in clinical
      trials and in the Expanded Access Program. This series illustrates that the
      benefits of gefitinib are not limited to patients selected for clinical trial
      participation but can be generalized to the broader population of patients with
      NSCLC.

PMID- 14667276
TI  - Sodium-wasting nephropathy caused by cisplatin in a patient with small-cell lung
      cancer.
AB  - We describe a case of severe hyponatremia following chemotherapy administration
      in a patient with small-cell lung cancer. There was no evidence of the syndrome
      of inappropriate antidiuretic hormone (SIADH) secretion. The clinical and
      laboratory findings were consistent with a sodium-wasting nephropathy
      complicating cisplatin administration. There are few well-documented reports of
      cisplatin-associated hyponatremia in the medical literature. We have summarized
      the relevant literature and attempted to define the differential diagnosis of
      hyponatremia in this setting. Most cases are accounted for by sodium-losing
      nephropathy of SIADH, but many reported cases contain insufficient data for
      classification. Appropriate attention to the evaluation of hyponatremia following
      platinum-based chemotherapy is needed to properly treat these conditions.

PMID- 14667277
TI  - Current status and future directions in breast cancer therapy.
AB  - With the majority of breast cancers in the United States diagnosed at an early
      stage, treatment is focused on cure and the prevention of relapse due to
      micrometastatic disease. Because systemic adjuvant therapy effectively prevents
      or delays some relapses and deaths in early-stage disease, this treatment
      approach has become widespread throughout most of the Western world. The mainstay
      of care for patients with breast cancer has become local therapy, consisting of
      surgery, radiation treatment, or both, along with adjuvant systemic therapy,
      which can include tamoxifen, combination chemotherapy, hormonal therapy, or a
      combination of these treatments. Despite this wide range of effective therapeutic
      interventions, therapy for metastatic disease remains focused on improving
      overall survival and maintaining quality of life. Future efforts are focused on
      improving current treatment options by optimizing dose regimens, developing
      effective chemotherapy combinations, using novel approaches such as HER2/neu
      antibody-directed therapies, and providing palliative care in the latter stages
      of disease.

PMID- 14667278
TI  - Current status of liposomal anthracycline therapy in metastatic breast cancer.
AB  - Doxorubicin is a mainstay for the treatment of metastatic breast cancer (MBC);
      however, its use is limited by toxicity, particularly cardiotoxicity. Novel drug
      delivery systems using liposomes have been developed to maintain the clinical
      utility of conventional doxorubicin while minimizing cardiotoxicity. Three
      liposomal anthracyclines have been developed: liposomal daunorubicin,
      nonpegylated liposomal doxorubicin, and pegylated liposomal doxorubicin.
      Liposomal daunorubicin, currently approved in the United States for the treatment
      of AIDS-related Kaposi sarcoma, has shown preliminary activity in MBC in a phase
      I trial; further investigation is ongoing. Nonpegylated liposomal doxorubicin,
      which is not available in the United States, has demonstrated activity similar to
      that of conventional doxorubicin (both as a single agent and in combinations).
      Pegylated liposomal doxorubicin has demonstrated activity in phase II and III
      trials when used alone or in combination with other chemotherapeutic agents in
      patients with MBC. It is currently approved in the United States and Europe for
      AIDS-related Kaposi sarcoma and platinum/paclitaxel-refractory ovarian carcinoma;
      in Europe and Canada, it is also approved as monotherapy for MBC. In addition,
      accumulating evidence suggests that the combination of liposomal anthracyclines
      (pegylated and nonpegylated) and trastuzumab is active, with acceptable toxicity.
      Based on these encouraging experiences, randomized clinical trials are ongoing or
      planned to further assess the therapeutic potential of pegylated liposomal
      doxorubicin as a single agent and in combination with other chemotherapeutic
      agents and targeted agents, such as trastuzumab, for MBC.

PMID- 14667280
TI  - Editorial: Looking beyond the obvious.

PMID- 14667279
TI  - Aromatase inhibitors in breast cancer therapy.
AB  - Recent advances have been made in the hormonal treatment of breast cancer with
      the advent of third-generation aromatase inhibitors (anastrozole, letrozole, and
      exemestane). These newer agents have substantial antitumor activity and appear to
      be as effective as tamoxifen, with fewer adverse effects. Recent reports indicate
      that anastrozole is more effective than tamoxifen as adjuvant endocrine therapy
      in postmenopausal women with breast cancer. This report provides an overview of
      the clinical trials conducted to date with the aromatase inhibitors as first- and
      second-line therapies, with an emphasis on recently updated analyses comparing
      anastrozole with tamoxifen in the adjuvant setting.

PMID- 14667281
TI  - Mitochondrial uptake of sestamibi distinguishes between normal, inflammatory
      breast changes, pre-cancers, and infiltrating breast cancer.
AB  - The evaluation of breast tissue using nuclear imaging is dependent upon the
      delivery and uptake of the isotope by breast tissue. This is dependent upon blood
      flow to the breast and functioning mitochondria. This 2-part study investigated
      (1) differences in uptake of sestamibi when blood flow is enhanced (breast
      enhanced scintigraphy test [BEST]), and (2) differences in isotope uptake in
      normal (Nl) breast tissue, inflammatory changes in breast tissue (ICB), and
      breast cancer (CA). In the first part of the study, 10 women were compared using
      both Miraluma and BEST imaging; in the second part, 195 people were studied using
      BEST imaging only. The results were compared with histopathologic specimens.
      Little difference was noted between Miraluma and BEST imaging in the first part.
      Women with ICB showed a statistically significant (P <.05) increase in isotope
      uptake using BEST imaging. This difference was even more significant (P <.005) in
      women with CA. During the second part of the study, BEST imaging demonstrated an
      exponential increase in tracer uptake. When maximal count activity was compared,
      there was a statistically significant (P <.001) difference between Nl and ICB,
      between ICB and atypia (A), and between A and CA. BEST imaging demonstrated
      significant increases in isotope delivery when compared with Miraluma imaging.
      These differences allowed differentiation of breast tissue, including the
      detection of early changes in breast tissue.

PMID- 14667282
TI  - Breast enhanced scintigraphy testing distinguishes between normal, inflammatory
      breast changes, and breast cancer: a prospective analysis and comparison with
      mammography.
AB  - The detection of breast cancer has primarily focused on anatomic findings,
      whereas assessment of physiologic information using nuclear imaging has been used
      for the detection of heart disease. Using this approach, the authors developed a
      method (breast enhanced scintigraphy test [BEST]) for differentiation of breast
      tissue by enhancing the delivery of isotope. To determine if this technique could
      distinguish between normal (Nl), inflammatory changes of the breast (ICB), and
      breast cancer (CA), 100 women were prospectively studied using BEST imaging, and
      results were compared with mammography and pathology findings using either biopsy
      or ductoscopy approaches. Mammography demonstrated a sensitivity and specificity
      of 69% and 84%, respectively. Using BEST imaging, maximal count activity (MCA)
      was able to distinguish between Nl, ICB, and CA. The results of 2-tailed t test
      analysis demonstrated statistically significant differences between Nl and ICB
      MCA (P </=.001); ICB and CA MCA(P </=.001); and N1 and CA MCA(P </=.001). Using
      MCA results obtained via BEST imaging, breast tissue was able to be
      differentiated, whereas mammography was able to detect breast cancer in only 69%
      of cases and incorrectly identified cancer in 16% of cases.

PMID- 14667283
TI  - Integrative tumor board: recently diagnosed lung cancer.

PMID- 14667284
TI  - The rise and fall of PC-SPES: new generation of herbal supplement, adulterated
      product, or new drug?

PMID- 14667285
TI  - PC-SPES: a brief overview.
AB  - PC-SPES is a botanically based dietary supplement that has been used by men
      following prostate cancer treatment to reduce prostate-specific antigen levels.
      It is a complex matrix comprising 8 herbs whose known chemistry and biology do
      not account for the observed clinical activity. Recent disclosures have forced
      the product to be withdrawn from the market. Aspects of previous scientific
      research on the product, including clinical information, are reviewed, and some
      suggestions are offered for the future scientific needs of this product. Some
      thoughts are also offered on what the recall of PC-SPES means for the future
      scientific directions of the dietary supplement industry.

PMID- 14667286
TI  - Integration of herbal medicine into modern medical practices: issues and
      prospects.
AB  - The integration of herbal medicine into modern medical practices including cancer
      treatments must take into account the interrelated issues of quality, safety, and
      efficacy. Quality is the paramount issue because it can affect the efficacy
      and/or safety of the herbal products being used. Current product quality ranges
      from very high to very low due to intrinsic, extrinsic, and regulatory factors.
      Intrinsically, species differences, organ specificity, diurnal and seasonal
      variations can affect the qualitative and quantitative accumulation of active
      chemical constituents in the source medicinal plants. Extrinsically,
      environmental factors; field collection methods such as cultivation, harvest,
      post-harvest transport and storage; manufacturing practices; inadvertent
      contamination and substitution; and intentional adulteration are contributing
      factors to the quality of herbal medicinal products. Source plant materials that
      are contaminated with microbes, microbial toxins, environmental pollutants, or
      heavy metals; or finished products that are adulterated with foreign toxic plants
      or synthetic pharmaceutical agents can lead to adverse events. Substandard source
      materials or finished products will yield therapeutically less effective agents.
      Herbal medicine quality can also be attributed to regulatory practices. In a
      number of countries, herbal medicines are unregulated, which has led to product
      quality differences. Product quality improvement may be achieved by implementing
      control measures from the point of medicinal plant procurement under good
      agricultural practices (GAPs) and the manufacture of the finished botanical
      products under good manufacturing practices (GMPs), plus post-marketing quality
      assurance surveillance. The lack of pharmacological and clinical data on the
      majority of herbal medicinal products is a major impediment to the integration of
      herbal medicines into conventional medical practices. For valid integration,
      pharmacological and especially, clinical studies, must be conducted on those
      plants lacking such data. Adverse events, including drug-herb interaction must
      also be monitored to promote a safe integration of efficacious herbal medicine
      into conventional medical practices.

PMID- 14667287
TI  - Point-counterpoint: the immune system in cancer.

PMID- 14667289
TI  - How to count curves: from nineteenth-century problems to twenty-first-century
      solutions.
AB  - Find the next term in the sequence 1, 1, 12, 620, 87304. This particular problem
      belongs to a branch of mathematics called enumerative geometry. This is concerned
      with curve-counting - counting the number of curves that can be drawn on a
      particular geometric object. The sequence above is easy to describe: each term
      represents the number of curves, with increasing complexity, one can draw though
      a certain number of points on a plane. Despite its simplicity, the problem
      remained unsolved for most of the twentieth century. The solution - a formula
      with which one may calculate any term in the series - was discovered only in the
      century's closing decade. This article will describe the above problem, and some
      of the unexpected mathematics and physics that was used in finding its solution
      [corrected]

PMID- 14667290
TI  - Pattern formation in large domains.
AB  - Pattern formation is a phenomenon that arises in a wide variety of physical,
      chemical and biological situations. A great deal of theoretical progress has been
      made in understanding the universal aspects of pattern formation in terms of
      amplitudes of the modes that make up the pattern. Much of the theory has sound
      mathematical justification, but experiments and numerical simulations over the
      last decade have revealed complex two-dimensional patterns that do not have a
      satisfactory theoretical explanation. This paper focuses on quasi-patterns, where
      the appearance of small divisors causes the standard theoretical method to fail,
      and ends with a discussion of other outstanding problems in the theory of two
      dimensional pattern formation in large domains.

PMID- 14667291
TI  - A black box at the end of the rainbow: searching for the perfect preconditioner.
AB  - Solution of large systems of linear algebraic equations is required in many areas
      of science and technology, and when several million unknown variables are
      involved, this apparently simple problem can assume gargantuan proportions.
      During the last half century many methods have been developed with the aim of
      providing reliable and cost-effective solutions to a wide range of system types.
      Many of these use 'pre-conditioners' to improve efficiency. The end-user, perhaps
      with limited knowledge of the mathematical basis, is presented with the task of
      choosing between a bewildering array of competing linear solvers and
      preconditioners. Here we survey currently available techniques and consider the
      feasibility of producing 'black-box' software capable of solving any linear
      system without further user input.

PMID- 14667292
TI  - Bayesian computation: a statistical revolution.
AB  - The 1990s saw a statistical revolution sparked predominantly by the phenomenal
      advances in computing technology from the early 1980s onwards. These advances
      enabled the development of powerful new computational tools, which reignited
      interest in a philosophy of statistics that had lain almost dormant since the
      turn of the century. In this paper we briefly review the historic and
      philosophical foundations of the two schools of statistical thought, before
      examining the implications of the reascendance of the Bayesian paradigm for both
      current and future statistical practice.

PMID- 14667293
TI  - Recent progress in Bose-Einstein condensation experiments.
AB  - When the atoms in a gas are cooled to extremely low temperatures, their quantum
      mechanical nature starts to dominate the properties of the whole gas. Under the
      appropriate conditions, the atoms will 'condense' into a single quantum state of
      the system-a phenomenon known as Bose-Einstein condensation (BEC). The resulting
      'condensate' behaves as a single, observable quantum-mechanical object. During
      the last decade, this new state of matter has displayed many remarkable
      properties. In this paper, we review some of the most recent experimental
      developments in the BEC field, highlighting the role of atomic interactions and
      the high degree of control with which condensates may be manipulated.

PMID- 14667294
TI  - Unconventional superconductivity and novel quantum order.
AB  - Superconductors have many unusual properties not observed in normal metals. The
      superconducting state is attributed to the pairing of electrons. Conventional
      forms of superconductivity are produced by distortions in the underlying crystal
      structure of the material. Recently, it has become evident that not all forms of
      superconductivity can be explained in this way. The way pairing occurs has to be
      redressed in these materials. Of particular interest is the interplay between
      magnetism and superconductivity and the consequences this may have on pair
      formation.

PMID- 14667295
TI  - Parametric light generation.
AB  - Since its invention more than 40 years ago, the laser has become an indispensable
      optical tool, capable of transforming light from its naturally incoherent state
      to a highly coherent state in space and time. Yet, due to fundamental
      limitations, operation of the laser remains confined to restricted spectral and
      temporal regions. Nonlinear optics can overcome this limitation by allowing
      access to new spectral and temporal regimes through the exploitation of suitable
      dielectric materials in combination with the laser. In particular, optical
      parametric oscillators are versatile coherent light sources with unique
      flexibility that can provide optical radiation across an entire spectral range
      from the ultraviolet to the far-infrared and over all temporal scales from
      continuous wave to the ultrafast femtosecond domain.

PMID- 14667296
TI  - Organic materials for second-harmonic generation: advances in relating structure
      to function.
AB  - The relationships between molecular structure and the nonlinear optical
      phenomenon second-harmonic generation (SHG) are discussed. New-found
      relationships built up from basic structural axioms that were deduced in the
      1970s and 1980s are the particular focus of this article, using structural
      results from X-ray and neutron-diffraction studies. The molecular and
      supramolecular manifestations of the SHG effect are borne out, although ways to
      optimize the effect on the molecular scale feature predominantly, since control
      of SHG on the supramolecular scale remains difficult given present limitations.
      The use of a variety of templates to generate head-to-tail oriented host-guest
      species thereby bypassing such limitations is described. The paper concludes with
      a look ahead at next generation 'octupolar' SHG-active compounds, the prediction
      of new series of SHG-active compounds via data-mining computational procedures,
      and developments in diffraction technology that may enable structural movies of a
      molecule to be captured during the SHG process. A practical assessment of the
      viability of organic SHG materials for industrial application is reviewed with a
      positive outcome, thus indicating a promising future for organic SHG materials.

PMID- 14667297
TI  - Recent advances in electron imaging, image interpretation and applications:
      environmental scanning electron microscopy.
AB  - One of the latest developments in electron microscopy is the environmental
      scanning electron microscope (ESEM), which enables soft, moist and/or
      electrically insulating materials to be viewed without pre-treatment, unlike
      conventional scanning electron microscopy, in which specimens must be solid, dry
      and usually electrically conductive. Such an advance has significant implications
      for studies of the 'native' surfaces of specimens including rocks and minerals,
      polymers, biological tissues and cells, food and pharmaceutical products,
      precious artefacts and forensic material, for example. Previous types of electron
      microscopes made scientists think carefully about the physics of electron-beam
      interactions with specimens and, hence, the interpretation of images. We now face
      additional factors influencing the emission and detection of electron signals,
      unique to the imaging of specimens in the partial vacuum of an ESEM. Just as
      importantly, we must consider the thermodynamic and kinetic stability of
      specimens, as appropriate, and explore the possibilities for new applications,
      particularly those of a dynamic nature. This paper briefly describes some of the
      issues involved and reviews the current state of understanding.

PMID- 14667298
TI  - The carbon nanocosmos: novel materials for the twenty-first century.
AB  - Carbon is one of the elements most abundant in nature. It is essential for living
      organisms and, as an element, occurs in several morphologies. Nowadays, carbon is
      encountered widely in our daily lives in its various forms and compounds, such as
      graphite, diamond, hydrocarbons, fibres, soot, oil, complex molecules, etc.
      However, in the last decade, carbon science and technology have enlarged its
      scope following the discovery of fullerenes (carbon nanocages) and the
      identification of carbon nanotubes (rolled graphene sheets). These novel
      nanostructures possess physico-chemical properties different from those of bulk
      graphite and diamond. It is expected that numerous technological applications
      will arise using such fascinating structures. This account summarizes the most
      relevant achievements regarding the production, properties and applications of
      nanoscale carbon structures and, in particular, of carbon nanotubes. It is
      believed that nanocarbons will be crucial for the development of emerging
      technologies in the following years.

PMID- 14667299
TI  - Molecular bioelectronics.
AB  - Biological macromolecules have evolved over many millions of years into
      structures primed, in some cases, for both specific surface recognition and
      facile, directional electron tunnelling. The redox-active centres of
      metalloproteins play a central role in photosynthesis and respiration. The
      processes by which constructive man-made interfaces to these moieties can be
      generated have advanced greatly during the past two decades or so. Together with
      recent advances in molecular manipulation, analyses and lithographic fabrication,
      this knowledge has led to us to the point where bioelectronic devices can be
      designed and interrogated with good levels of reproducibility.

PMID- 14667300
TI  - Ultrafast nanomagnets: seeing data storage in a new light.
AB  - Magnetic materials provide the most important form of erasable data storage for
      information technology today. The demand for increased storage capacity has
      caused bit sizes and features of the read-write transducers to be reduced to the
      nanoscale. However, increased storage capacity is only useful if there is a
      commensurate reduction in the time taken to read and write the data. In this
      article, the basic principles that determine the behaviour of nanomagnetic
      materials are introduced and their use in data-storage systems is described.
      Particular attention is paid to processes that limit the speed of operation of
      the data-storage system. It is shown that optical pump-probe experiments may be
      used to characterize dynamic magnetic processes with femtosecond temporal
      resolution. The macroscopic magnetization of a ferromagnet can be made to precess
      in response to an optically triggered magnetic field pulse, leading to reduced
      switching times. Alternatively, an ultrashort laser pulse may be used to
      manipulate the magnitude of the magnetization on femtosecond time-scales, leading
      to an ultrafast demagnetization in certain ferromagnets, and providing new
      insight into magnetotransport phenomena. Finally, the outlook for increased
      record and replay rates is assessed and the prospect of further use of optical
      techniques within magnetic data-storage technology is discussed.

PMID- 14667301
TI  - Near-field microscopy: throwing light on the nanoworld.
AB  - Optical microscopy with nanoscale resolution, beyond that which is possible with
      conventional diffraction-limited microscopy, may be achieved by scanning a
      nanoantenna in close proximity to a sample surface. This review will first aim to
      provide an overview of the basic principles of this technique of scanning near
      field optical microscopy (SNOM), before moving on to consider the most widely
      implemented form of this microscopy, in which the sample is illuminated through a
      small aperture held less than 10 nm from the sample surface for optical imaging
      with a resolution of ca. 50 nm. As an example of the application of this
      microscopy, the results of SNOM measurements of light-emitting polymer
      nanostructures are presented. In particular, SNOM enables the unambiguous
      identification of the different phases present in the nanostructures, through the
      local analysis of the fluorescence from the polymers. The exciting new
      possibilities for high-resolution optical microscopy and spectroscopy promised by
      apertureless SNOM techniques are also considered. Apertureless SNOM may involve
      local scattering of light from a sample surface by a tip, local enhancement of an
      optical signal by a metal tip, or the use of a fluorescent molecule or
      nanoparticle attached to a tip as a local optical probe of a surface. These new
      optical nanoprobes offer the promise of optical microscopy with true nanometre
      spatial resolution.

PMID- 14667302
TI  - Intelligent machines in the twenty-first century: foundations of inference and
      inquiry.
AB  - The last century saw the application of Boolean algebra to the construction of
      computing machines, which work by applying logical transformations to information
      contained in their memory. The development of information theory and the
      generalization of Boolean algebra to Bayesian inference have enabled these
      computing machines, in the last quarter of the twentieth century, to be endowed
      with the ability to learn by making inferences from data. This revolution is just
      beginning as new computational techniques continue to make difficult problems
      more accessible. Recent advances in our understanding of the foundations of
      probability theory have revealed implications for areas other than logic. Of
      relevance to intelligent machines, we recently identified the algebra of
      questions as the free distributive algebra, which will now allow us to work with
      questions in a way analogous to that which Boolean algebra enables us to work
      with logical statements. In this paper, we examine the foundations of inference
      and inquiry. We begin with a history of inferential reasoning, highlighting key
      concepts that have led to the automation of inference in modern machine-learning
      systems. We then discuss the foundations of inference in more detail using a
      modern viewpoint that relies on the mathematics of partially ordered sets and the
      scaffolding of lattice theory. This new viewpoint allows us to develop the logic
      of inquiry and introduce a measure describing the relevance of a proposed
      question to an unresolved issue. Last, we will demonstrate the automation of
      inference, and discuss how this new logic of inquiry will enable intelligent
      machines to ask questions. Automation of both inference and inquiry promises to
      allow robots to perform science in the far reaches of our solar system and in
      other star systems by enabling them not only to make inferences from data, but
      also to decide which question to ask, which experiment to perform, or which
      measurement to take given what they have learned and what they are designed to
      understand.

PMID- 14667303
TI  - Modelling the world in real time: how robots engineer information.
AB  - Programming robots and other autonomous systems to interact with the world in
      real time is bringing into sharp focus general questions about representation,
      inference and understanding. These artificial agents use digital computation to
      interpret the data gleaned from sensors and produce decisions and actions to
      guide their future behaviour. In a physical system, however, finite computational
      resources unavoidably impose the need to approximate and make selective use of
      the information available to reach prompt deductions. Recent research has led to
      widespread adoption of the methodology of Bayesian inference, which provides the
      absolute framework to understand this process fully via modelling as informed,
      fully acknowledged approximation. The performance of modern systems has improved
      greatly on the heuristic methods of the early days of artificial intelligence. We
      discuss the general problem of real-time inference and computation, and draw on
      examples from recent research in computer vision and robotics: specifically
      visual tracking and simultaneous localization and mapping.

PMID- 14667304
TI  - Engineering the next generation of large-area displays: prospects and pitfalls.
AB  - Considerable effort is currently expounded on the development and improvement of
      the myriad display technologies that have come to the market place. In this
      paper, several key questions are addressed in the development of the future
      generation of large-area field-emission-based displays based on semiconducting
      amorphous carbon thin films and carbon nanotubes (CNTs). The development of
      carbon-based cathodes has to date proceeded along empirical lines, with attempts
      to correlate the variation of field-emission characteristics with changes in
      deposition or post-deposition processing parameters, often without a full
      explanation being forthcoming. In addition, there have been incidents of
      incorrect interpretation of some of the results, due to a lack of appreciation of
      the significant differences between the different types of amorphous carbon film
      that exist. It is only recently that a fuller understanding of the different
      electron-emission mechanisms has begun to emerge through an understanding of the
      roles played by the electrical and structural inhomogeneity at nanometre level.
      This 'intrinsic dielectric inhomogeneity' is shown to possess some remarkable
      electronic properties, which also have important consequences for extrinsic
      inhomogeneous nanometre systems such as CNT and CNT-polymer-composite-based
      displays. The future outlook for broad-area displays based on amorphous carbon
      and CNTs is also addressed.

PMID- 14667305
TI  - Foundations for offshore wind turbines.
AB  - An important engineering challenge of today, and a vital one for the future, is
      to develop and harvest alternative sources of energy. This is a firm priority in
      the UK, with the government setting a target of 10% of electricity from renewable
      sources by 2010. A component central to this commitment will be to harvest
      electrical power from the vast energy reserves offshore, through wind turbines or
      current or wave power generators. The most mature of these technologies is that
      of wind, as much technology transfer can be gained from onshore experience.
      Onshore wind farms, although supplying 'green energy', tend to provoke some
      objections on aesthetic grounds. These objections can be countered by locating
      the turbines offshore, where it will also be possible to install larger capacity
      turbines, thus maximizing the potential of each wind farm location. This paper
      explores some civil-engineering problems encountered for offshore wind turbines.
      A critical component is the connection of the structure to the ground, and in
      particular how the load applied to the structure is transferred safely to the
      surrounding soil. We review previous work on the design of offshore foundations,
      and then present some simple design calculations for sizing foundations and
      structures appropriate to the wind-turbine problem. We examine the deficiencies
      in the current design approaches, and the research currently under way to
      overcome these deficiencies. Designs must be improved so that these alternative
      energy sources can compete economically with traditional energy suppliers.

PMID- 14667306
TI  - Multilayered materials: a palette for the materials artist.
AB  - Developments in the understanding of how materials behave enable us to design
      material structures to display specified properties. We introduce multilayered
      materials as systems in which new properties, not found in their constituents in
      bulk form, can emerge. The importance of transmission electron microscopy to
      determine structure-property relationships in nanoscale multilayers through
      characterization of their atomic and electronic structure is emphasized. Two
      examples of technologically useful multilayer systems are considered in more
      detail: hard coatings made from nitride multilayer films and the new structures
      and magnetic properties that are found in some metal multilayer systems. Finally,
      we discuss the future developments that are required to fully exploit the novel
      properties found in multilayered materials.

PMID- 14667307
TI  - The concept of drift and its application to multiphase and multibody problems.
AB  - The concept of drift is built around understanding how a rigid body moving in a
      straight line distorts a material sheet in an unbounded perfect fluid. As the
      body moves from infinity through a material sheet, which is initially
      perpendicular to the direction of translation of the body, the sheet is
      permanently distorted. Darwin showed that the 'drift' volume, D(f), formed
      between the distorted and undistorted sheet is equal to C(m)V, where the added
      mass coefficient, C(m), characterizes the shape of the body whose volume is V.
      Darwin's result is important for two reasons: first, it provides a means of
      quantifying how dyed fluid is transported from one place to another and
      dispersed; second, it provides a fundamental Lagrangian coordinate system to
      study inhomogeneous inviscid problems. The aim of this article is to review
      Darwin's contribution to fluid mechanics. By drawing on recent experimental
      measurements of drift and the drift volume, we aim to demonstrate how Darwin's
      drift concept has developed and to describe its broader significance for
      multiphase and multibody problems.

PMID- 14667308
TI  - New directions in fluid dynamics: non-equilibrium aerodynamic and microsystem
      flows.
AB  - Fluid flows that do not have local equilibrium are characteristic of some of the
      new frontiers in engineering and technology, for example, high-speed high
      altitude aerodynamics and the development of micrometre-sized fluid pumps,
      turbines and other devices. However, this area of fluid dynamics is poorly
      understood from both the experimental and simulation perspectives, which hampers
      the progress of these technologies. This paper reviews some of the recent
      developments in experimental techniques and modelling methods for non-equilibrium
      gas flows, examining their advantages and drawbacks. We also present new results
      from our computational investigations into both hypersonic and microsystem flows
      using two distinct numerical methodologies: the direct simulation Monte Carlo
      method and extended hydrodynamics. While the direct simulation approach produces
      excellent results and is used widely, extended hydrodynamics is not as well
      developed but is a promising candidate for future more complex simulations.
      Finally, we discuss some of the other situations where these simulation methods
      could be usefully applied, and look to the future of numerical tools for non
      equilibrium flows.

PMID- 14667309
TI  - Solar sailing: mission applications and engineering challenges.
AB  - Solar sailing is emerging as a promising form of advanced spacecraft propulsion,
      which can enable exciting new space-science mission concepts. By exploiting the
      momentum transported by solar photons, solar sails can perform high-energy orbit
      transfer manoeuvres without the need for reaction mass. Missions such as
      planetary-sample return, multiple small-body rendezvous and fast missions to the
      outer Solar System can therefore be enabled with the use of only a modest launch
      vehicle. In addition, new families of highly non-Keplerian orbits have been
      identified that are unique to solar sails, and can enable new ways of performing
      space-science missions. While the opportunities presented by solar sailing are
      appealing, engineering challenges are still to be solved before the technology
      finally comes to fruition.

PMID- 14667310
TI  - Introduction.
AB  - It is embarrassing that 95% of the Universe is unaccounted for. Galaxies and
      larger-scale cosmic structures are composed mainly of "dark matter", whose nature
      is still unknown. Favoured candidates are weakly interacting particles that have
      survived from the very early Universe, but more exotic options cannot be
      excluded. (There are strong arguments that the dark matter is not composed of
      baryons.) Intensive experimental searches are being made for the "dark" particles
      (which pervade our entire Galaxy), but we have indirect clues to their nature
      too. Inferences from galactic dynamics and gravitational lensing allow
      astronomers to "map" the dark-matter distribution; comparison with numerical
      simulations of Galaxy formation can constrain (for example) the particle
      velocities and collision cross-sections; and, of course, progress in
      understanding the extreme physics of the ultra-early Universe could offer clues
      to what particles might have existed then, and how many would have survived. The
      mean cosmic density of dark matter (plus baryons) is now pinned down to be only
      ca.30% of the so-called critical density corresponding to a "flat" Universe.
      However, other recent evidence-microwave background anisotropies, complemented by
      data on distant supernovae-reveals that our Universe actually is "flat", but that
      its dominant ingredient (ca.70% of the total mass energy) is something quite
      unexpected: "dark energy" pervading all space, with negative pressure. We now
      confront two mysteries. (i) Why does the Universe have three quite distinct basic
      ingredients-baryons, dark matter and dark energy-in the proportions (roughly) 5%,
      25% and 70%? (ii) What are the (almost certainly profound) implications of the
      "dark energy" for fundamental physics?

PMID- 14667311
TI  - Cosmic microwave background snapshots: pre-WMAP and post-WMAP.
AB  - We highlight the remarkable evolution in the cosmic microwave background (CMB)
      power spectrum C(l) as a function of multipole l over the past few years, and in
      the cosmological parameters for minimal inflation models derived from it: from
      anisotropy results before 2000; in 2000 and 2001 from Boomerang, Maxima and the
      Degree Angular Scale Interferometer (DASI), extending l to approximately 1000;
      and in 2002 from the Cosmic Background Imager (CBI), Very Small Array (VSA),
      ARCHEOPS and Arcminute Cosmology Bolometer Array Receiver (ACBAR), extending l to
      approximately 3000, with more from Boomerang and DASI as well. Pre-WMAP (pre
      Wilkinson Microwave Anisotropy Probe) optimal band powers are in good agreement
      with each other and with the exquisite one-year WMAP results, unveiled in
      February 2003, which now dominate the l less, similar 600 bands. These CMB
      experiments significantly increased the case for accelerated expansion in the
      early Universe (the inflationary paradigm) and at the current epoch (dark energy
      dominance) when they were combined with "prior" probabilities on the parameters.
      The minimal inflation parameter set, [omega(b), omega(cdm), Omega(tot),
      Omega(Lambda), n(s), tau(C), sigma(8)], is applied in the same way to the
      evolving data. C(l) database and Monte Carlo Markov Chain (MCMC) methods are
      shown to give similar values, which are highly stable over time and for different
      prior choices, with the increasing precision best characterized by decreasing
      errors on uncorrelated "parameter eigenmodes". Priors applied range from weak
      ones to stronger constraints from the expansion rate (HST-h), from cosmic
      acceleration from supernovae (SN1) and from galaxy clustering, gravitational
      lensing and local cluster abundance (LSS). After marginalizing over the other
      cosmic and experimental variables for the weak + LSS prior, the pre-WMAP data of
      January 2003 compared with the post-WMAP data of March 2003 give Omega(tot) =
      1.03(-0.04)(+0.05) compared with 1.02(-0.03)(+0.04), consistent with (non
      Baroque) inflation theory. Adding the flat Omega(tot) = 1 prior, we find a nearly
      scale-invariant spectrum, n(s) = 0.95(-0.04)(+0.07) compared with 0.97(
      0.02)(+0.02). The evidence for a logarithmic variation of the spectral tilt is
      less than or approximately 2sigma. The densities are for: baryons, omega(b)
      identical with Omega(b)h(2) = 0.0217(-0.002)(+0.002) (compared with 0.0228(
      0.001)(+0.001)), near the Big Bang nucleosynthesis (BBN) estimate of 0.0214 +/-
      0.002; CDM, omega(cdm) = Omega(cdm)h(2) = 0.126(-0.012)(+0.012) (compared with
      0.121(-0.010)(+0.010)); the substantial dark (unclustered) energy, Omega(Lambda)
      approximately 0.66(-0.09)(+0.07) (compared with 0.70(-0.05)(+0.05)). The dark
      energy pressure-to-density ratio w(Q) is not well constrained by our weak + LSS
      prior, but adding SN1 gives w(Q) less than or approximately -0.7 for January 2003
      and March 2003, consistent with the w(Q) = -1 cosmological constant case. We find
      sigma(8) = 0.89(-0.07)(+0.06) (compared with 0.86(-0.04)(+0.04)), implying a
      sizable Sunyaev-Zel'dovich (SZ) effect from clusters and groups; the high-l power
      found in the January 2003 data suggest sigma(8) approximately 0.94(-0.16)(+0.08)
      is needed to be SZ-compatible.

PMID- 14667312
TI  - Dark energy: recent observations and future prospects.
AB  - Dark energy presents us with a challenging puzzle: understanding the new physics
      seen in the acceleration of the expansion of the Universe. Measurements using
      type-Ia supernovae (SNe) first detected this acceleration, and this approach
      remains the most direct route to studying the details of the Universe's expansion
      history that can teach us more about the nature of the dark energy. Such
      measurements are, however, extremely demanding in both precision and accuracy,
      since the different dark-energy models predict very small differences in the
      expansion history. While several cosmological probes may reach the required
      statistical uncertainties, the key measurement limit will be the systematic
      uncertainty. The supernova-measurement approach has the advantage of well-studied
      systematic uncertainties, allowing a next-generation experiment to be pursued. We
      briefly review the progress to date and examine the promise of future surveys
      with large numbers of SNe and well-bounded systematics.

PMID- 14667313
TI  - Large-scale structure and matter in the Universe.
AB  - This paper summarizes the physical mechanisms that encode the type and quantity
      of cosmological matter in the properties of large-scale structure, and reviews
      the application of such tests to current datasets. The key lengths of the horizon
      size at matter-radiation equality and at last scattering determine the total
      matter density and its ratio to the relativistic density; acoustic oscillations
      can diagnose whether the matter is collisionless, and small-scale structure or
      its absence can limit the mass of any dark-matter relic particle. The most
      stringent constraints come from combining data on present-day galaxy clustering
      with data on CMB anisotropies. Such an analysis breaks the degeneracies inherent
      in either dataset alone, and proves that the Universe is very close to flat. The
      matter content is accurately consistent with pure cold dark matter, with ca. 25%
      of the critical density, and fluctuations that are scalar only, adiabatic and
      scale invariant. It is demonstrated that these conclusions cannot be evaded by
      adjusting either the equation of state of the vacuum, or the total relativistic
      density.

PMID- 14667314
TI  - A quintessential introduction to dark energy.
AB  - Most of the energy in the Universe consists of some form of dark energy that is
      gravitationally self-repulsive and that is causing the expansion of the Universe
      to accelerate. The possible candidates are a vacuum energy density (or,
      equivalently, a cosmological constant) and quintessence, a time-evolving,
      spatially inhomogeneous component with negative pressure. In this review, we
      focus on quintessence and ideas on how it might solve the cosmic coincidence
      problem, how it might be distinguished observationally from a cosmological
      constant, and how it may affect the overall cosmic history of the Universe.

PMID- 14667315
TI  - Cusps and rotation curves in cold-dark-matter haloes.
AB  - I report on recent numerical simulations designed to study the inner structure of
      cold-dark-matter (CDM) haloes. This work confirms and extends earlier indications
      that the mass profiles of CDM haloes are roughly independent of mass and that the
      dark-matter density appears to diverge in a central "cusp". Our simulations also
      show that CDM halo-density profiles get increasingly shallow inwards down to the
      innermost radius (r(min)) resolved by the simulations, with no evidence for
      convergence to a well-defined asymptotic value (beta(0)) of the logarithmic
      slope. The dark mass contained within r(min) places strong constraints on
      beta(0); cusps as steep as beta(0) approximately -1.5 are clearly ruled out in
      our highest resolution simulations, although beta(0) less, similar -1 is
      consistent with the numerical data. The circular-velocity curves of the simulated
      CDM haloes are generally consistent with the rotation curves of low-surface
      brightness (LSB) galaxies in the literature, but there are also some clearly
      discrepant cases. This disagreement has been interpreted as excluding the
      presence of cusps, but I argue that it may just reflect the difference between
      circular velocity and rotation speed likely to arise in gaseous discs embedded
      within realistic triaxial haloes. The perceived challenge to the CDM paradigm
      stemming from LSB rotation curves may thus plausibly result from the complex
      three-dimensional structure of CDM haloes, and might be resolved without appeal
      to a drastic revision of the paradigm.

PMID- 14667316
TI  - Neutrino mass measurements.
AB  - Before we can be sure we have a dark-matter problem we have to first be certain
      that no known particle can account for the missing matter. The last possibility
      has long been the neutrino, which, while massless in the Standard Model of
      particle physics, is the second most numerous particle in the Universe (after the
      photon) and thus (if massive) a potential source of substantial unaccounted for
      mass. Recent neutrino oscillation measurements have, in fact, confirmed that the
      Standard Model is incomplete and that neutrinos have mass. However, recent
      measurements have confirmed that the resulting mass is insufficient for neutrinos
      to make up the bulk of the dark matter. In fact, observations of the matter
      distribution in the Universe are now competing with laboratory measurements in
      their sensitivity to the absolute masses of neutrinos. The article discusses all
      these measurements and gives some guesses about where we may get in our
      measurements of neutrino masses in the future.

PMID- 14667317
TI  - Experimental searches for galactic halo axions.
AB  - A very light axion would be copiously produced during the Big Bang as a zero
      temperature Bose gas, and it would possess vanishingly small couplings to matter
      and radiation. It thus represents an ideal cold dark matter candidate. Galactic
      halo axions may be detected by their resonant conversion to microwave photons in
      a high-Q cavity permeated by a strong magnetic field. A large-scale search for
      the axion is ongoing in the US with sufficient sensitivity to see axions of
      plausible model couplings. Dramatic breakthroughs in the development of near
      quantum limited superconducting quantum interference device amplifiers promise to
      improve the sensitivity of the experiment by a factor of 30 in the near future.
      In Japan, a group has been developing a Rydberg atom single-quantum detector as
      an alternative to linear amplifiers for a microwave-cavity axion experiment.
      Should the axion be discovered, the predicted fine structure in the axion signal
      would be rich in information about the history of galactic formation.

PMID- 14667318
TI  - Indirect detection of weakly interacting massive particles.
AB  - Several experiments are performing searches for dark matter in the Galaxy in the
      form of weakly interacting massive particles (WIMPs). A major search technique is
      to look for secondary particles originating from the annihilation of pairs of
      WIMPs at various locations in the Galaxy. The nature of the experiment depends on
      the species of secondary particle searched for. This paper outlines the
      motivation for such searches and describes the present experimental status.
      Existing data from searches from positron, anti-proton, gamma-ray and neutrino
      detectors will be presented, together with details of future experiments under
      construction.

PMID- 14667319
TI  - Direct WIMP detection with cryogenic detectors.
AB  - Cryogenic detectors have been developed since the mid 1980s and have been applied
      successfully to dark-matter searches since the mid 1990s. Among the advantages of
      cryogenic detectors are their high sensitivity to nuclear recoil, their low
      detection thresholds, the wide choice of target materials and the possibility of
      implementing event type recognition on an event-by-event basis. I explain the
      basics of cryogenic detectors, review various implementations, discuss advantages
      and drawbacks and give an overview of current dark-matter-search experiments
      based upon cryogenic detectors.

PMID- 14667320
TI  - Direct detection of weakly interacting massive particles using non-cryogenic
      techniques.
AB  - A flux of weakly interacting neutral particles incident on the Earth would
      produce occasional nuclear-recoil events in any material. These could be detected
      as scintillation or ionization pulses in suitable target materials. Expected
      rates are in the range 1-10(-4) events kg(-1) d(-1). These must be distinguished
      from much higher rates due to backgrounds from gamma and beta background, even in
      deep underground locations. Methods of uniquely identifying nuclear recoils are
      described using crystal scintillators, scintillation and ionization processes in
      liquid xenon, and ionization tracks in gases. World progress on these techniques
      and future prospects are summarized. A possible future weakly interacting massive
      particle detector based on mechanical recoil of suspended microgranules is
      proposed which, with advances in nanotechnology, could eventually be extended to
      the detection of low-energy relic neutrinos.

PMID- 14667321
TI  - Dark matter and dark energy: summary and future directions.
AB  - This paper reviews the progress reported at the Discussion Meeting and advertises
      some possible future directions in our drive to understand dark matter and dark
      energy. Additionally, a first attempt is made to place in context the exciting
      new results from the Wilkinson Microwave Anisotropy Probe satellite, which were
      published shortly after this meeting. In the first part of this paper, pieces of
      observational evidence shown here that bear on the amounts of dark matter and
      dark energy are reviewed. Subsequently, particle candidates for dark matter are
      mentioned, and detection strategies are discussed. Finally, ideas are presented
      for calculating the amounts of dark matter and dark energy, and possibly relating
      them to laboratory data.

PMID- 14667322
TI  - A comparative analysis of the modification of sexual desire of users of oral
      hormonal contraceptives and intrauterine contraceptive devices.
AB  - OBJECTIVE: To compare the influence of oral hormonal contraceptives (OCs) and the
      use of intrauterine contraceptive devices (IUDs) on the modification of sexual
      desire. MATERIALS AND METHODS: A prospective observational study of 1073 women
      using OCs or an IUD at the Family Planning Center 'Marina Alta' in Alicante,
      Spain. In order to evaluate the relative risk regarding the decrease in libido
      attributed to each contraceptive method, a logistic regression analysis was
      undertaken which considered the factors of age adjustment, level of studies,
      family planning information, relationship with partner, age when sexual
      relationships were initiated, parity, contraceptive method previously used and
      the duration of use of the contraceptive method. RESULTS: No differences in the
      decrease of sexual desire were observed between the use of the OC and IUD (odds
      ratio (OR) 1.32; 95% confidence interval (CI) 0.70-2.49), yet differences were
      noted, however, in relation to age (OR 1.05; 95% CI 1.01-1.10). Although these
      differences were not statistically significant, a high level of awareness
      regarding family planning was shown to increase sexual desire when compared to a
      lower level of information on this subject (OR 0.64; 95% CI 0.41-1.01). Sexual
      desire was seen to decrease if the quality of the relationship with the partner
      was average (OR 2.24; 95% CI 1.36-3.69) or poor (OR 4.69; 95% CI 1.93-11.4).
      Nulliparous women showed a greater decrease in sexual desire in relation to women
      who had already given birth (OR 1.57; 95% CI 1.00-2.47). Sexual desire was
      greater if the contraceptive method had already been in use for 6-12 months (OR
      0.41; 95% CI 0.17-0.98). CONCLUSIONS: Sexual desire does not vary in relation to
      the use of OCs or IUDs, yet it does decrease with age, in nulliparous women and
      in those with an average or poor relationship with their partner. Furthermore,
      sexual desire shows an increase between the first 6 and 12 months of
      contraceptive treatment.

PMID- 14667323
TI  - Frequency of bacterial vaginosis among women attending for intrauterine device
      insertion at an inner-city family planning clinic.
AB  - The aim of this study was to investigate the rate of bacterial vaginosis in women
      attending an inner-city family planning clinic for intrauterine device (IUD)
      insertion. In a population of 86 women, eight (9.3%) and 20 (23.2%) were found to
      have bacterial vaginosis according to the criteria of Amsel and Nugent,
      respectively. Sensitivity, specificity, positive and negative predictive values
      were calculated in relation to bacterial vaginosis for Amsel's criteria. The
      detection of clue cells demonstrated excellent sensitivity (85%). Positive amine
      test and vaginal discharge demonstrated poor sensitivity (50% and 55%,
      respectively). Our results suggest that Gram staining of vaginal specimens may be
      of use to identify the presence of bacterial vaginosis prior to IUD insertion.

PMID- 14667324
TI  - Why do university students use hormonal emergency contraception?
AB  - OBJECTIVES: To establish why university students in Finland, who have easy access
      to well-affordable health services, still use hormonal emergency contraception.
      METHOD: All students who sought emergency contraception in the Tampere Student
      Health Station during the period from 1 September 2000 to 31 December 2001
      received a questionnaire on their use of it. Of the total, 114 (67%) were
      returned. RESULTS: Two-thirds of respondents experienced condom failure, and the
      remainder used no contraception. In open answers, respondents gave many
      explanations as to why they had used no contraception, e.g. having been over
      passionate or drunk. CONCLUSION: Finnish students use emergency contraception,
      but to no great extent. Our results indicate that service providers should pay
      attention to sexual health in the full sense but not omit to give detailed advice
      on condom use during counselling.

PMID- 14667325
TI  - Health personnel perceptions about emergency contraception in primary health-care
      centers.
AB  - OBJECTIVE: The aim of this study was to assess the knowledge, attitudes and
      practices regarding emergency contraception in primary health-care workers.
      METHODS: This survey was conducted among health-care personnel in 20 primary
      healthcare centers in Izmir. A self-administered questionnaire was completed by
      190 health-care personnel (doctors, nurses and midwives). Specific questions
      regarding knowledge of emergency contraception were asked. RESULTS: In all, 22%
      of personnel had received specialized training in family planning. Of the
      respondents, 53.7% had heard of emergency contraception. General practitioners
      were much more well informed than other health personnel. CONCLUSION: Primary
      health-care personnel play a significant role in the provision of reproductive
      health care for women. There is a need to educate primary health-care personnel
      further about emergency contraception.

PMID- 14667326
TI  - Analysis of risk factors associated with uterine perforation by intrauterine
      devices.
AB  - OBJECTIVE: To determine the risk factors for intrauterine devices (IUDs) being
      displaced into the abdominal cavity. METHODS: This prospective follow-up study
      was conducted between 1996 and 2002, at the family planning clinic of a referral
      hospital. All 8343 women who had a copper T-380A IUD inserted underwent
      ultrasound examination after 1 year. Relative risk estimates and logistic
      regression analyses were performed to determine the risk factors associated with
      uterine perforation by intrauterine devices. RESULTS: Eighteen uterine
      perforations occurred during the study, giving an incidence of 2.2 per 1000
      insertions. When the time elapsed after the last delivery until IUD insertion is
      considered, postplacental insertion and insertion after 6 months postpartum were
      found not to increase the risk of uterine perforation. However, IUD insertion 0-3
      months postpartum increased the risk of uterine perforation (odds ratio (OR)
      11.7, 95% confidence interval (CI) 2.8-49.2) as did insertions at 3-6 months
      postpartum (OR 13.2, CI 2.8-62). Increasing parity decreased the risk (OR 0.04,
      CI 0.01-0.1) and increasing number of abortions increased the risk (OR 2.1, CI
      1.2-3.6). CONCLUSION: It is safer to postpone IUD insertion until 6 months after
      delivery.

PMID- 14667327
TI  - Perception of efficacy and safety as determinants for use and discontinuation of
      birth control methods in Muslim Jordanian women.
AB  - OBJECTIVE: This study was conducted to identify the perceptions of working Muslim
      Jordanian women regarding the efficacy and safety of their contraceptive methods,
      and whether these perceptions affected method choice or discontinuation. METHODS:
      A prospective study on 207 married working women of reproductive age was
      conducted between March and June 2002. RESULTS: The majority of women were using
      an intrauterine device (IUD), fewer were using traditional methods and oral
      contraceptive pills. Effectiveness was the main reason for choosing IUD and pill
      methods, while concerns about safety were the main reason for discontinuation.
      Safety was the main reason for choosing traditional methods and poor efficacy was
      the reason for discontinuation. CONCLUSION: Health-care professionals need to
      increase the use of proper contraceptive methods and compliance by providing
      counseling services and correcting any misperceptions regarding birth control
      methods before and during use.

PMID- 14667328
TI  - Use of an oral contraceptive containing drospirenone in an extended regimen.
AB  - As well as providing reliable contraception, modern low-dose oral contraceptives
      may offer some non-contraceptive advantages. Positive effects on problems such as
      edema with weight increase and breast tenderness, bloating, dysmenorrhea, and an
      improvement in skin and hair condition have been reported in several studies
      using an oral contraceptive containing drospirenone. If these disorders are cycle
      dependent, use of the contraceptive in an extended regimen may be of additional
      benefit. The study reported in this paper followed 1433 women, 175 of whom took
      the drospirenone-containing pill continuously for between 42 and 126 days. Some
      symptoms of the premenstrual syndrome were influenced very satisfactorily by
      administration in an extended regimen.

PMID- 14667329
TI  - An unusual cause of vesical stone: a migrant intrauterine device.
AB  - Intrauterine contraceptives devices have been in use for many years. Although
      perforation of the uterus by an intrauterine device is not uncommon, intravesical
      migration with secondary stone formation is a rare complication. We report on a
      32-year-old woman in whom an intrauterine contraceptive device (Copper T)
      migrated from her uterus into the bladder. She had lower urinary tract symptoms
      for nearly 2 years but sought no treatment. The onset of hematuria and fear of
      cancer prompted her to seek treatment. On investigation, a vesical stone was
      discovered that had formed on a copper T contraceptive device. It was removed via
      suprapubic cystostomy. In any woman in whom an intrauterine device is fitted and
      who presents with lower urinary tract symptoms, the possibility of intravesical
      migration of the device should be included in the differential diagnosis.

PMID- 14667330
TI  - The automatic pilot of honeybees.
AB  - Using scanning harmonic radar, we make visible for the first time the complete
      trajectories of "goal-vector" flights in honeybees. We demonstrate that bees
      captured at an established feeding station, and released elsewhere, nevertheless
      embark on the previously learned vector flight that would have taken them
      directly home from the station, had they not been artificially displaced. Almost
      all of the bees maintained accurate compensation for lateral wind drift, and many
      completed the full length of the vector flight before starting to search for
      their hive. Our results showed that bees tend to disregard landscape cues during
      these vector flights, at least initially, and rely on the "optic flow" of the
      ground beneath them, and their sun compass, to judge both direction and distance.

PMID- 14667331
TI  - Spread of cattle led to the loss of matrilineal descent in Africa: a
      coevolutionary analysis.
AB  - Matrilineal descent is rare in human societies that keep large livestock.
      However, this negative correlation does not provide reliable evidence that
      livestock and descent rules are functionally related, because human cultures are
      not statistically independent owing to their historical relationships (Galton's
      problem). We tested the hypothesis that when matrilineal cultures acquire cattle
      they become patrilineal using a sample of 68 Bantu- and Bantoid-speaking
      populations from sub-Saharan Africa. We used a phylogenetic comparative method to
      control for Galton's problem, and a maximum-parsimony Bantu language tree as a
      model of population history. We tested for coevolution between cattle and
      descent. We also tested the direction of cultural evolution--were cattle acquired
      before matriliny was lost? The results support the hypothesis that acquiring
      cattle led formerly matrilineal Bantu-speaking cultures to change to patrilineal
      or mixed descent. We discuss possible reasons for matriliny's association with
      horticulture and its rarity in pastoralist societies. We outline the daughter
      biased parental investment hypothesis for matriliny, which is supported by data
      on sex, wealth and reproductive success from two African societies, the
      matrilineal Chewa in Malawi and the patrilineal Gabbra in Kenya.

PMID- 14667332
TI  - Multiple overseas dispersal in amphibians.
AB  - Amphibians are thought to be unable to disperse over ocean barriers because they
      do not tolerate the osmotic stress of salt water. Their distribution patterns
      have therefore generally been explained by vicariance biogeography. Here, we
      present compelling evidence for overseas dispersal of frogs in the Indian Ocean
      region based on the discovery of two endemic species on Mayotte. This island
      belongs to the Comoro archipelago, which is entirely volcanic and surrounded by
      sea depths of more than 3500 m. This constitutes the first observation of endemic
      amphibians on oceanic islands that did not have any past physical contact to
      other land masses. The two species of frogs had previously been thought to be
      nonendemic and introduced from Madagascar, but clearly represent new species
      based on their morphological and genetic differentiation. They belong to the
      genera Mantidactylus and Boophis in the family Mantellidae that is otherwise
      restricted to Madagascar, and are distinguished by morphology and mitochondrial
      and nuclear DNA sequences from mantellid species occurring in Madagascar. This
      discovery permits us to update and test molecular clocks for frogs distributed in
      this region. The new calibrations are in agreement with previous rate estimates
      and indicate two further Cenozoic transmarine dispersal events that had
      previously been interpreted as vicariance: hyperoliid frogs from Africa to
      Madagascar (Heterixalus) and from Madagascar to the Seychelles islands
      (Tachycnemis). Our results provide the strongest evidence so far that overseas
      dispersal of amphibians exists and is no rare exception, although vicariance
      certainly retains much of its importance in explaining amphibian biogeography.

PMID- 14667333
TI  - Fitness reduction and potential extinction of wild populations of Atlantic
      salmon, Salmo salar, as a result of interactions with escaped farm salmon.
AB  - The high level of escapes from Atlantic salmon farms, up to two million fishes
      per year in the North Atlantic, has raised concern about the potential impact on
      wild populations. We report on a two-generation experiment examining the
      estimated lifetime successes, relative to wild natives, of farm, F(1) and F(2)
      hybrids and BC(1) backcrosses to wild and farm salmon. Offspring of farm and
      "hybrids" (i.e. all F(1), F(2) and BC(1) groups) showed reduced survival compared
      with wild salmon but grew faster as juveniles and displaced wild parr, which as a
      group were significantly smaller. Where suitable habitat for these emigrant parr
      is absent, this competition would result in reduced wild smolt production. In the
      experimental conditions, where emigrants survived downstream, the relative
      estimated lifetime success ranged from 2% (farm) to 89% (BC(1) wild) of that of
      wild salmon, indicating additive genetic variation for survival. Wild salmon
      primarily returned to fresh water after one sea winter (1SW) but farm and
      'hybrids' produced proportionately more 2SW salmon. However, lower overall
      survival means that this would result in reduced recruitment despite increased
      2SW fecundity. We thus demonstrate that interaction of farm with wild salmon
      results in lowered fitness, with repeated escapes causing cumulative fitness
      depression and potentially an extinction vortex in vulnerable populations.

PMID- 14667334
TI  - The effect of foraging parameters on the probability that a dive is successful.
AB  - In this paper, we investigate the foraging decisions of an animal that dives to
      obtain its food. It might seem reasonable to use the probability that the diver
      is successful in any dive as an indicator of habitat quality. We use a dynamic
      model of optimal prey choice to show that this interpretation of diving success
      is not generally valid. In particular, we show that diving success is not
      directly proportional to the overall rate of gain that can be achieved in an
      environment. Furthermore, some environmental factors can have a non-monotonic
      effect on the probability of success. For example, as the travel time to the
      foraging area increases, the probability of success may first increase and then
      decrease. We point out that the same conclusions are likely to apply in the
      context of mate choice, i.e. the probability of getting a mate may not be an
      indicator of the quality of the environment in terms of reproductive success.

PMID- 14667335
TI  - Speed versus accuracy in collective decision making.
AB  - We demonstrate a speed versus accuracy trade-off in collective decision making.
      House-hunting ant colonies choose a new nest more quickly in harsh conditions
      than in benign ones and are less discriminating. The errors that occur in a harsh
      environment are errors of judgement not errors of omission because the colonies
      have discovered all of the alternative nests before they initiate an emigration.
      Leptothorax albipennis ants use quorum sensing in their house hunting. They only
      accept a nest, and begin rapidly recruiting members of their colony, when they
      find within it a sufficient number of their nest-mates. Here we show that these
      ants can lower their quorum thresholds between benign and harsh conditions to
      adjust their speed-accuracy trade-off. Indeed, in harsh conditions these ants
      rely much more on individual decision making than collective decision making. Our
      findings show that these ants actively choose to take their time over judgements
      and employ collective decision making in benign conditions when accuracy is more
      important than speed.

PMID- 14667336
TI  - A fitness cost of learning ability in Drosophila melanogaster.
AB  - Maintenance of substantial genetic variation for learning ability in many animal
      populations suggests that learning ability has fitness costs, but there is little
      empirical evidence for them. In this paper, we demonstrate an evolutionary trade
      off between learning ability and competitive ability in Drosophila melanogaster.
      We show that the evolution of an improved learning ability in replicated
      experimental fly populations has been consistently associated with a decline of
      larval competitive ability, compared with replicated control populations. The
      competitive ability was not affected by crossing of the replicate populations
      within each selection regime, excluding differential inbreeding as a potential
      confounding factor. Our results provide evidence for a constitutive fitness cost
      of learning ability, i.e. one that is paid irrespective of whether or not the
      learning ability is actually used.

PMID- 14667337
TI  - Immune response inhibits associative learning in insects.
AB  - In vertebrates, it is well established that there are many intricate interactions
      between the immune system and the nervous system, and vice versa. Regarding
      insects, until now little has been known about the link between these two
      systems. Here, we present behavioural evidence indicating a link between the
      immune system and the nervous system in insects. We show that otherwise non
      infected honeybees whose immune systems are challenged by a non-pathogenic
      immunogenic elicitor lipopolysaccharide (LPS) have reduced abilities to associate
      an odour with sugar reward in a classical conditioning paradigm. The cost of an
      immune response therefore not only affects survival of the host, as previously
      shown, but also everyday behaviour and memory formation.

PMID- 14667338
TI  - Adaptive innate immunity? Responsive-mode prophylaxis in the mealworm beetle,
      Tenebrio molitor.
AB  - A primary infection by a parasite may indicate a higher risk of being reinfected
      in the near future (since infection may indicate that enemies are becoming more
      abundant). Acquired immunity does not exist in invertebrates despite the fact
      that they also face increased risks of reinfection following primary exposure.
      However, when subjected to immune insult, insects can produce immune responses
      that persist for long enough to provide prophylaxis. Because these immune
      responses are costly, persistence must be maintained through a selective
      advantage. We tested for the possibility that these long-lasting immune responses
      provided increased resistance to later infections by experimentally mimicking a
      primary immune insult (pre-challenge) in larvae of the mealworm beetle, Tenebrio
      molitor, with lipopolysaccharides (LPS) prior to early or late exposure to spores
      of the entomopathogenic fungus Metarhizium anisopliae. We found that pre
      challenged larvae produced a long-lasting antimicrobial response, which provided
      a survival benefit when the larvae were exposed to fungal infection. These
      results suggest that the observed response is functionally "adaptive".

PMID- 14667339
TI  - Correlated evolution between host immunity and parasite life histories in
      primates and oxyurid parasites.
AB  - Maturation time is a pivotal life-history trait of parasitic nematodes,
      determining adult body size, as well as daily and total fecundity. Recent
      theoretical work has emphasized the influence of prematurational mortality on the
      optimal values of age and size at maturity in nematodes. Eosinophils are a family
      of white blood cells often associated with infections by parasitic nematodes.
      Although the role of eosinophils in nematode resistance is controversial, recent
      work has suggested that the action of these immune effectors might be limited to
      the larval stages of the parasite. If eosinophils act on larval survival, one
      might predict, in line with theoretical models, that nematode species living in
      hosts with large eosinophil numbers should show reduced age and size at maturity.
      We tested this prediction using the association between the pinworms (Oxyuridae,
      Nematoda) and their primate hosts. Pinworms are highly host specific and are
      expected to be involved in a coevolutionary process with their hosts. We found
      that the body size of female parasites was negatively correlated with eosinophil
      concentration, whereas the concentration of two other leucocyte families
      neutrophils and lymphocytes-was unrelated to female body size. Egg size of
      parasites also decreased with host eosinophil concentration, independently of
      female size. Male body size was unrelated to host immune parameters. Primates
      with the highest immune defence, therefore, harbour small female pinworms laying
      small eggs. These results are in agreement with theoretical expectations and
      suggest that life histories of oxyurid parasites covary with the immune defence
      of their hosts. Our findings illustrate the potential for host immune defence as
      a factor driving parasite life-history evolution.

PMID- 14667340
TI  - Experimental manipulation of egg carotenoids affects immunity of barn swallow
      nestlings.
AB  - The yolk of bird eggs contains maternal carotenoids that may act as antioxidants
      thus influencing offspring performance and survival. However, to our knowledge,
      this hypothesis has not been subjected to experimental tests and the function of
      transmission of carotenoids to the egg is largely unknown. We directly
      manipulated the concentration of the main carotenoid (lutein) in the eggs of barn
      swallows (Hirundo rustica) and analysed the effect of experimental manipulation
      on growth of nestlings and two fundamental components of their acquired immunity.
      Nestlings hatched from lutein-inoculated eggs had larger T-cell-mediated immune
      response compared with those of two control groups. T-cell-mediated immune
      response predicted nestling survival until fledging. However, lutein inoculation
      did not affect antibody response to an immunogen, body mass, tarsus length or
      plumage development. Nestling body mass and plumage development declined with egg
      laying order, but the effects of lutein inoculation were independent of egg
      laying order for all traits. Our results show that maternal yolk carotenoids can
      have a major effect in promoting a fundamental component of immunity that
      predicts offspring survival and suggests that adaptive early maternal effects can
      be mediated by transmission of antioxidants to eggs.

PMID- 14667341
TI  - Melanin-based plumage coloration and flight displays in plovers and allies.
AB  - Plovers and their allies exhibit an impressive diversity of melanin-based plumage
      patterns ranging from non-melanized to completely melanized species. We use
      phylogenetic comparative methods to test whether melanization has evolved in
      relation to sexual selection for attracting mates, to selection for signalling
      territory defence, or to natural selection for camouflage. First, according to
      sexual-selection theory, melanized plumage has evolved to amplify the courtship
      displays of males. As predicted by this hypothesis, we found that males with
      aerial displays had more melanized plumage than males of ground-displaying
      species. In addition, sexual dimorphism in melanization was greater in species
      with display flights than in species with ground displays. Second, melanization
      may have evolved through social interactions to signal competitive ability in
      territory defence. We did not find evidence for this hypothesis, since breeding
      density was unrelated to the melanization of either sex. Finally, melanized
      plumage may camouflage the incubating parent. The latter hypothesis was not
      supported, since melanization was unrelated either to the darkness of nest
      substrate or the extent of vegetation cover. Taken together, our results are most
      consistent with the sexual-selection hypothesis, and suggest that melanized
      plumage has evolved to enhance the aerial displays of male plovers.

PMID- 14667342
TI  - Analysis of diversification: combining phylogenetic and taxonomic data.
AB  - The estimation of diversification rates using phylogenetic data has attracted a
      lot of attention in the past decade. In this context, the analysis of incomplete
      phylogenies (e.g. phylogenies resolved at the family level but unresolved at the
      species level) has remained difficult. I present here a likelihood-based method
      to combine partly resolved phylogenies with taxonomic (species-richness) data to
      estimate speciation and extinction rates. This method is based on fitting a birth
      and-death model to both phylogenetic and taxonomic data. Some examples of the
      method are presented with data on birds and on mammals. The method is compared
      with existing approaches that deal with incomplete phylogenies. Some applications
      and generalizations of the approach introduced in this paper are further
      discussed.

PMID- 14667343
TI  - A supertree of early tetrapods.
AB  - A genus-level supertree for early tetrapods is built using a matrix
      representation of 50 source trees. The analysis of all combined trees delivers a
      long-stemmed topology in which most taxonomic groups are assigned to the tetrapod
      stem. A second analysis, which excludes source trees superseded by more
      comprehensive studies, supports a deep phylogenetic split between lissamphibian
      and amniote total groups. Instances of spurious groups are rare in both analyses.
      The results of the pruned second analysis are mostly comparable with those of a
      recent, character-based and large-scale phylogeny of Palaeozoic tetrapods.
      Outstanding areas of disagreement include the branching sequence of lepospondyls
      and the content of the amniote crown group, in particular the placement of
      diadectomorphs as stem diapsids. Supertrees are unsurpassed in their ability to
      summarize relationship patterns from multiple independent topologies. Therefore,
      they might be used as a simple test of the degree of corroboration of nodes in
      the contributory analyses. However, we urge caution in using them as a
      replacement for character-based cladograms and for inferring macroevolutionary
      patterns.

PMID- 14667344
TI  - Plastic reproductive strategies in a clonal marine invertebrate.
AB  - Plastic reproductive allocation may allow individuals to maximize their fitness
      when conditions vary. Mate availability is one condition that may determine the
      fitness of an individual's allocation strategy. Using a variety of methods, I
      detected evidence of plastic allocation to asexual (clonal) reproduction in
      response to mate availability in the brittle star Ophiactis savignyi. There were
      more mature individuals in populations in which both sexes were present, and
      clones from these populations had fewer clone-mates than clones from single-sex
      populations. Animals placed with mates in a field experiment divided less
      frequently than animals without a mate. These findings demonstrate that animals
      reduce their allocation to asexual reproduction when mates are present and when a
      loss of fecundity associated with cloning would decrease offspring production.
      This plasticity is probably adaptive because it maximizes sexual-reproductive
      potential when fertilization is more likely, but maximizes survival of the clone
      when mates are absent and gametes are unlikely to be converted to offspring.

PMID- 14667345
TI  - Exhaustive sample set among Viverridae reveals the sister-group of felids: the
      linsangs as a case of extreme morphological convergence within Feliformia.
AB  - Although molecular studies have helped to clarify the phylogeny of the
      problematic family Viverridae, a recent phylogenetic investigation based on
      cytochrome b (cyt b) has excluded the Asiatic linsangs (genus Prionodon) from the
      family. To assess the phylogenetic position of the Asiatic linsangs within the
      Feliformia, we analysed an exhaustive taxonomic sample set with cyt b and newly
      produced transthyretin intron I sequences (TR-I-I). TR-I-I alone and cyt b +TR-I
      I combined (maximum-likelihood analysis) highly support the position of Asiatic
      linsangs as sister-group of the Felidae. The estimation of minimum divergence
      dates from molecular data suggests a splitting event ca. 33.3 million years (Myr)
      ago, which lends support to historical assertions that the Asiatic linsangs are
      "living fossils" that share a plesiomorphic morphotype with the Oligocene
      feliform Paleoprionodon. The African linsang is estimated to appear more than 20
      Myr later and represents the sister-group of the genus Genetta. Our phylogenetic
      results illustrate numerous morphological convergences of "diagnostic" characters
      among Feliformia that might be problematic for the identification of fossil taxa.
      The morphotype reappearance from the Asiatic to the African linsangs suggests
      that the genome of the Feliformia conserved its potential ability of expression
      for a peculiar adaptive phenotype throughout evolution, in this case arboreality
      and hypercarnivory in tropical forest.

PMID- 14667346
TI  - Immune function across generations: integrating mechanism and evolutionary
      process in maternal antibody transmission.
AB  - The past 30 years of immunological research have revealed much about the
      proximate mechanisms of maternal antibody transmission and utilization, but have
      not adequately addressed how these issues are related to evolutionary and
      ecological theory. Much remains to be learned about individual differences within
      a species in maternal antibody transmission as well as differences among species
      in transmission or utilization of antibodies. Similarly, maternal-effects theory
      has generally neglected the mechanisms by which mothers influence offspring
      phenotype. Although the environmental cues that generate maternal effects and the
      consequent effects for offspring phenotype are often well characterized, the
      intermediary physiological and developmental steps through which the maternal
      effect is transmitted are generally unknown. Integration of the proximate
      mechanisms of maternal antibody transmission with evolutionary theory on maternal
      effects affords an important opportunity to unite mechanism and process by
      focusing on the links between genetics, environment and physiology, with the
      ultimate goal of explaining differences among individuals and species in the
      transfer of immune function from one generation to the next.

PMID- 14667347
TI  - Cryptic speciation on the high seas; global phylogenetics of the copepod family
      Eucalanidae.
AB  - Few genetic data are currently available to assess patterns of population
      differentiation and speciation in planktonic taxa that inhabit the open ocean. A
      phylogenetic study of the oceanic copepod family Eucalanidae was undertaken to
      develop a model zooplankton taxon in which speciation events can be confidently
      identified. A global survey of 20 described species (526 individuals) sampled
      from 88 locations worldwide found high levels of cryptic diversity at the species
      level. Mitochondrial (16S rRNA, CO1) and nuclear (ITS2) DNA sequence data support
      12 new genetic lineages as highly distinct from other populations with which they
      are currently considered conspecific. Out of these 12, at least four are new
      species. The circumglobal, boundary current species Rhincalanus nasutus was found
      to be a cryptic species complex, with genetic divergence between populations
      unrelated to geographic distance. 'Conspecific' populations of seven species
      exhibited varying levels of genetic differentiation between Atlantic and Pacific
      basins, suggesting that continental landmasses form barriers to dispersal for a
      subset of circumglobal species. A molecular phylogeny of the family based on both
      mitochondrial (16S rRNA) and nuclear (ITS2, 18S rRNA) gene loci supports
      monophyly of the family Eucalanidae, all four eucalanid genera and the 'pileatus'
      and 'subtenuis' species groups.

PMID- 14667348
TI  - Evolution of the olfactory code in the Drosophila melanogaster subgroup.
AB  - The Drosophila melanogaster subgroup has been the focus of numerous studies about
      evolution. We address the question of how the olfactory code has evolved among
      the nine sister species. By using in vivo electrophysiological measurements, so
      called single-cell recordings, we have established the ligand affinity of a
      defined subset of olfactory receptor neurons (ORNs) across all nine species. We
      show that the olfactory code as relayed by the investigated subset of ORNs is
      conserved to a striking degree. Distinct shifts in the code have occurred only
      within the simulans clade. However, these shifts are restricted to an altered
      tuning profile of the same single ORN type in all three of the simulans siblings
      and a more drastic change unique to D. sechellia, involving a complete loss of
      one sensillum type in favour of another. The alterations observed in D. sechellia
      may represent a novel host-specific adaptation to its sole host, morinda fruit
      (Morinda citrifolia). The overall high degree of similarity of the code within
      the subgroup is intriguing when considering the great variety in distributions as
      well as in habitat and host choice of the siblings, factors that could greatly
      affect the olfactory system.

PMID- 14667349
TI  - Natural image statistics mediate brightness 'filling in'.
AB  - Although the human visual system can accurately estimate the reflectance (or
      lightness) of surfaces under enormous variations in illumination, two
      equiluminant grey regions can be induced to appear quite different simply by
      placing a light-dark luminance transition between them. This illusion, the Craik
      Cornsweet-O'Brien (CCOB) effect, has been taken as evidence for a low-level
      'filling-in' mechanism subserving lightness perception. Here, we present evidence
      that the mechanism responsible for the CCOB effect operates not via propagation
      of a neural signal across space but by amplification of the low spatial frequency
      (SF) structure of the image. We develop a simple computational model that relies
      on the statistics of natural scenes actively to reconstruct the image that is
      most likely to have caused an observed series of responses across SF channels.
      This principle is tested psychophysically by deriving classification images (CIs)
      for subjects' discrimination of the contrast polarity of CCOB stimuli masked with
      noise. CIs resemble 'filled-in' stimuli; i.e. observers rely on portions of the
      stimuli that contain no information per se but that correspond closely to the
      reported perceptual completion. As predicted by the model, the filling-in process
      is contingent on the presence of appropriate low SF structure.

PMID- 14667350
TI  - A simple visual system without neurons in jellyfish larvae.
AB  - Earlier detailed studies of cnidarian planula larvae have revealed a simple
      nervous system but no eyes or identifiable light sensing structures. Here, we
      describe the planula of a box jellyfish, Tripedalia cystophora, and report that
      these larvae have an extremely simple organization with no nervous system at all.
      Their only advanced feature is the presence of 10-15 pigment-cup ocelli, evenly
      spaced across the posterior half of the larval ectoderm. The ocelli are single
      cell structures containing a cup of screening pigment filled with presumably
      photosensory microvilli. These rhabdomeric photoreceptors have no neural
      connections to any other cells, but each has a well-developed motor-cilium,
      appearing to be the only means by which light can control the behaviour of the
      larva. The ocelli are thus self-contained sensory-motor entities, making a
      nervous system superfluous.

PMID- 14667351
TI  - Month of birth predicted reproductive success and fitness in pre-modern Canadian
      women.
AB  - Conditions experienced during early development affect human health and survival
      in adulthood, but whether such effects have consequences for fitness is not
      known. One surrogate for early conditions is month of birth, which is known to
      influence health and survival in many human populations. We show that in
      nineteenth century Canada, month of birth predicted a woman's fitness measured by
      the number of grandchildren produced, with the genetic contribution to the
      following generations by women born in different months differing by over seven
      grandchildren. This difference was mainly caused by differences in the
      reproductive rates of both mothers and their offspring, rather than differences
      in their survival. Women born in the best months of the year had longer
      reproductive lifespans, larger numbers of live births and raised more offspring
      to adulthood than those who were born in the worst months. Furthermore, the
      offspring of those women born in the best months also had greater reproductive
      rates, suggesting that month of birth also influenced a mother's ability to
      invest in her offspring. Our results suggest that early conditions may have
      important consequences for human lifetime reproductive performance within and
      between generations, and that timing of birth had large effects on fitness in
      this rural community.

PMID- 14667352
TI  - Give unto others: genetically unrelated cotton-top tamarin monkeys preferentially
      give food to those who altruistically give food back.
AB  - Altruistic food giving among genetically unrelated individuals is rare in nature.
      The few examples that exist suggest that when animals give food to unrelated
      others, they may do so on the basis of mutualistic or reciprocally altruistic
      relationships. We present the results of four experiments designed to tease apart
      the factors mediating food giving among genetically unrelated cotton-top tamarins
      (Saguinus oedipus), a cooperatively breeding New World primate. In experiment 1
      we show that individuals give significantly more food to a trained conspecific
      who unilaterally gives food than to a conspecific who unilaterally never gives
      food. The apparent contingency of the tamarins' food-giving behaviour motivated
      the design of experiments 2-4. Results from all three experiments show that
      altruistic food giving is mediated by prior acts of altruistic food giving by a
      conspecific. Specifically, tamarins do not give food to unrelated others when the
      food received in the past represents the by-product of another's selfish actions
      (experiments 2 and 3) or when a human experimenter gives them food (experiment 4)
      as did the unilateral altruist in experiment 1. By contrast, if one tamarin gives
      another food without obtaining any immediate benefit, then the recipient is more
      likely to give food in return. Overall, results show that tamarins altruistically
      give food to genetically unrelated conspecifics, discriminate between altruistic
      and selfish actions, and give more food to those who give food back. Tamarins
      therefore have the psychological capacity for reciprocally mediated altruism.

PMID- 14667353
TI  - Reducing a cost of traumatic insemination: female bedbugs evolve a unique organ.
AB  - The frequent wounding of female bedbugs (Cimex lectularius: Cimicidae) during
      copulation has been shown to decrease their fitness, but how females have
      responded to this cost in evolutionary terms is unclear. The evolution of a
      unique anatomical structure found in female bedbugs, the spermalege, into which
      the male's intromittent organ passes during traumatic insemination, is a possible
      counteradaptation to harmful male traits. Several functions have been proposed
      for this organ, and we test two hypotheses related to its role in sexual
      conflict. We examine the hypotheses that the spermalege functions to (i) defend
      against pathogens introduced during traumatic insemination; and (ii) reduce the
      costs of wound healing during traumatic insemination. Our results support the
      'defence against pathogens' hypothesis, suggesting that the evolution of this
      unique cimicid organ resulted, at least partly, from selection to reduce the
      costs of mating-associated infection. We found no evidence that the spermalege
      reduces the costs of wound healing.

PMID- 14667354
TI  - Costly traumatic insemination and a female counter-adaptation in bed bugs.
AB  - Male bed bugs pierce females through the body wall and inseminate directly into
      the body cavity. It has previously been shown that such traumatic insemination
      carries costs for females, and sexual conflict regarding the mode of insemination
      should thus propel male-female coevolution. Since males accumulate sexually
      antagonistic adaptations, females should evolve counter-adaptations that
      efficiently abate the costs to females of sexual interactions. Yet, unambiguous
      experimental evidence for female counter-adaptations is lacking. In bed bugs, the
      spermalege (a highly modified region of the abdomen where the male usually
      pierces the female) may represent a female counter-adaptation. We assess the
      female costs of traumatic insemination by varying the rate of insemination on the
      one hand, and the rate and mode of piercing trauma to females on the other. Our
      results show that female mating costs are not extreme-elevated mating rate
      shortened female lifespan but had no significant effect on lifetime egg
      production. More importantly, additional abdominal piercing in the spermalege had
      no effect on females whereas even a very low rate of such piercing outside the
      spermalege reduced female lifetime egg production by 50%. Thus, females are well
      counter-adapted to the intrusive mode of insemination exhibited by male bed bugs
      and the costs of elevated mating are comparable with those in other insects, as
      predicted by theory. We therefore demonstrate that the spermalege efficiently
      reduces the direct costs of piercing trauma to females, and hence provide
      experimental evidence for a female counter-adaptation to a sexually antagonistic
      male trait.

PMID- 14667355
TI  - Slow pace of life in tropical sedentary birds: a common-garden experiment on four
      stonechat populations from different latitudes.
AB  - It has been hypothesized that organisms living at different latitudes or in
      different environments adjust their metabolic activity to the prevailing
      conditions. However, do differences in energy turnover simply represent a
      phenotypic adaptation to the local environment, or are they genetically based? To
      test this, we obtained nestling stonechats (Saxicola torquata) from equatorial
      Kenya (0 degrees N), Ireland (51.5 degrees N), Austria (47.5 degrees N) and
      Kazakhstan (51.5 degrees N). Birds were hand-raised and kept in Andechs, Germany.
      We measured their resting metabolic rates (RMR) and locomotor activity at an age
      of ca. 14 months (July) and 20 months (January), when birds went through
      postnuptial moult (July), and neither moulted nor exhibited enlarged gonads or
      migratory activity (January). RMR was generally higher during moult, but differed
      among populations: RMR was lowest in the resident Kenyan birds, higher in mostly
      sedentary Irish birds, and highest in migratory Austrian and Kazakhstan birds.
      Thus our data demonstrate that even in birds kept from early life under common
      garden conditions, the 'pace of life', as indicated by metabolic turnover, is
      lower in sedentary tropical than in north-temperate migratory individuals of the
      same species. Such intrinsically low energy expenditure in sedentary tropical
      birds may have important implications for slow development, delayed senescence
      and high longevity in many tropical organisms.

PMID- 14667356
TI  - Multiple male traits interact: attractive bower decorations facilitate attractive
      behavioural displays in satin bowerbirds.
AB  - Sexually selected male courtship displays often involve multiple behavioural and
      physical traits, but little is known about the function of different traits in
      mate choice. Here, we examine female courtship behaviours to learn how male
      traits interact to influence female mating decisions. In satin bowerbirds
      (Ptilonorhynchus violaceus), successful males give highly aggressive, intense
      behavioural displays without startling females. Males do this by modulating their
      displays in response to female crouching, which signals the display intensity
      that females will tolerate without being startled. Females typically visit
      multiple males for multiple courtships before choosing a mate, and females show
      differing tolerance for intense displays during their first courtship with each
      male. We test three hypotheses that may explain this: (i) familiarity with the
      courting male; (ii) the order of the courtship in mate-searching; and (iii) the
      attractiveness of the courting male. We found that females are more tolerant of
      intense displays during first courtships with attractive males; this increased
      female tolerance may allow attractive males to give higher intensity courtship
      displays that further enhance their attractiveness. We then examined why this is
      so, finding evidence that females are less likely to be startled by males with
      better physical displays (bower decorations), and this reduced startling then
      contributes to male courtship success. This role of physical displays in
      facilitating behavioural displays suggests a novel mechanism by which multiple
      physical and behavioural traits may influence female choice.

PMID- 14667357
TI  - Climate variation and regional gradients in population dynamics of two hole
      nesting passerines.
AB  - Latitudinal gradients in population dynamics can arise through regional variation
      in the deterministic components of the population dynamics and the stochastic
      factors. Here, we demonstrate an increase with latitude in the contribution of a
      large-scale climate pattern, the North Atlantic Oscillation (NAO), to the
      fluctuations in size of populations of two European hole-nesting passerine
      species. However, this influence of climate induced different latitudinal
      gradients in the population dynamics of the two species. In the great tit the
      proportion of the variability in the population fluctuations explained by the NAO
      increased with latitude, showing a larger impact of climate on the population
      fluctuations of this species at higher latitudes. In contrast, no latitudinal
      gradient was found in the relative contribution of climate to the variability of
      the pied flycatcher populations because the total environmental stochasticity
      increased with latitude. This shows that the population ecological consequences
      of an expected climate change will depend on how climate affects the
      environmental stochasticity in the population process. In both species, the
      effects will be larger in those parts of Europe where large changes in climate
      are expected.

PMID- 14667358
TI  - Antimicrobial egg cleaning by the fringed darter (Perciformes: Percidae:
      Etheostoma crossopterum): implications of a novel component of parental care in
      fishes.
AB  - Broad-spectrum antimicrobial compounds have recently been identified in the
      epidermal mucus of fishes and probably serve as a first line of defence against
      microbial pathogens. Because of the ubiquitous nature of fungi and bacteria in
      aquatic systems, defence against these pathogens should be required throughout
      the lifespan of fishes, including the egg stage. We conducted experiments on
      Etheostoma crossopterum (Percidae: Catonotus), the fringed darter, to determine
      if the presence of a guarding male inhibits microbial colonization of eggs. Based
      on results from a combination of in-stream experiments, in vitro microbial
      assays, and morphological characteristics and behaviour of breeding males, we
      propose that antimicrobial egg cleaning by the guarding male is an effective
      component of parental care in these fish. Although innate antimicrobial compounds
      have been identified in a variety of organisms ranging from insects to
      vertebrates, integration of these compounds into a species's reproductive life
      history has been identified only in a small number of insect species. The results
      from this study not only indicate that E. crossopterum males provide a novel form
      of vertebrate parental care, but also have implications regarding the evolution
      of parental care in fishes and transitional evolutionary stages from no parental
      care to male parental care.

PMID- 14667359
TI  - Species difference in adaptive use of public information in sticklebacks.
AB  - Animals foraging on variable food sources can refine their estimates of patch
      quality by monitoring the success of others (i.e. collect 'public information').
      Here, we show that both three-spined sticklebacks (Gasterosteus aculeatus) and
      nine-spined sticklebacks (Pungitius pungitius) use past cues provided by others
      to locate food but only nine-spined sticklebacks use prior public information to
      assess patch quality, regardless of whether demonstrators were conspecifics or
      heterospecifics. Moreover, nine-spined but not three-spined sticklebacks
      preferentially hid in vegetation during the demonstration, a position from which
      they could observe both patches simultaneously and collect public information. We
      conclude that species differences in the use of public information can be
      explained by variations in habitat choice and response to predation. Our findings
      expand current understanding of the scope of public-information use in animals by
      showing that fishes can use public-information in a foraging context and from
      heterospecifics. The study suggests that public-information use is an adaptation
      that allows animals vulnerable to predation to acquire valuable foraging
      information at low risk.

PMID- 14667360
TI  - Current transport of leatherback sea turtles (Dermochelys coriacea) in the ocean.
AB  - While the long-distance movements of pelagic vertebrates are becoming known
      thanks to satellite telemetry, the factors determining their courses have hardly
      been investigated. We have analysed the effects of oceanographic factors on the
      post-nesting movements of three satellite-tracked leatherback turtles
      (Dermochelys coriacea) moving in the southwest Indian Ocean. By superimposing the
      turtle tracks on contemporaneous images of sea-surface temperatures and sea
      height anomalies, we show that currentrelated features dominate the shape of the
      reconstructed routes. After an initial offshore movement, turtles moved along
      straight routes when in the core of the current, or executed loops within eddies.
      Large parts of the routes were strikingly similar to those of surface drifters
      tracked in the same region. These findings document that long-lasting oceanic
      movements of marine turtles may be shaped by oceanic currents.

PMID- 14667361
TI  - The paradox of the parasites: implications for biological invasion.
AB  - The enemy-release hypothesis for biological invasions supposes that invasive
      species may be more successful in their introduced ranges than in their native
      ranges owing to the absence of coevolved natural enemies. Recent studies
      supporting this hypothesis have found that introduced plants and animals are less
      parasitized in their introduced ranges than in their native ranges. Expanding on
      this theory, I hypothesize that the role of enemy release may differ among the
      introduction, establishment and spread phases of an invasion. I present a simple
      model indicating that parasite release is unlikely to greatly affect the chance
      of establishment in populations with and without an immune subpopulation. The
      specific numerical relationship between the number of individuals introduced and
      the chance of establishment depends on a relationship between virulence, here
      conceptualized as the chance for the extinction of a lineage, and the fraction of
      the population infected at introduction. These results support the idea of a
      'filter effect' in which different biological processes regulate the different
      phases of an invasion.

PMID- 14667362
TI  - Sex as a response to oxidative stress: the effect of antioxidants on sexual
      induction in a facultatively sexual lineage.
AB  - The evolution of sex is one of the long-standing unsolved problems in biology.
      Although in many lineages sex is an obligatory part of the life cycle and is
      associated with reproduction, in prokaryotes and many lower eukaryotes, sex is
      facultative, occurs in response to stress and often involves the formation of a
      stress-resistant dormant form. The proximate and ultimate causes of the
      connection between stress and sex in facultatively sexual lineages are unclear.
      Because most forms of stress result in the overproduction of cellular reactive
      oxygen species (ROS), we address the hypothesis that this connection involves ROS
      and possibly reflects the ancestral role of sex as an adaptive response to the
      damaging effects of stress-induced ROS (i.e. oxidative stress). Here, we report
      that two antioxidants inhibit sexual induction in a facultatively sexual species 
      the multicellular green alga, Volvox carteri. Furthermore, the nature of the sex
      response and the effect of an iron chelator on sexual induction are consistent
      with sex being a response to the DNA-damaging effects of ROS. In addition, we
      present preliminary data to suggest that sex, cell-cycle arrest and apoptosis are
      alternative responses to increased levels of oxidative stress.

PMID- 14667363
TI  - Representing occluded objects in the human infant brain.
AB  - One of the most striking phenomena in cognitive development has been the apparent
      failure of infants to show 'object permanence' in manual reaching tasks although
      they show evidence for representing hidden objects in studies measuring looking
      times. We report a neural correlate of object permanence in six-month-old
      infants: a burst of gamma-band EEG activity over the temporal lobe that occurs
      during an occlusion event and when an object is expected to appear from behind an
      occluder. We interpret this burst as being related to the infants' mental
      representation of the occluded object.

PMID- 14667364
TI  - Evidence from rhesus macaques suggests that male coloration plays a role in
      female primate mate choice.
AB  - Male animals of many species use conspicuous coloration to attract mates. Among
      mammals, primates possess the most brilliant secondary sexual coloration.
      However, whether colour plays a part in primate female mate choice remains
      unknown. Adult male rhesus macaques undergo a hormonally regulated increased
      reddening of facial and anogenital skin during their mating season. We
      experimentally investigated whether red male facial coloration is preferred by
      simultaneously presenting female rhesus macaques (n = 6) with computer
      manipulated pale and red versions of 24 different male faces. The duration and
      direction of gaze were measured to discern visual preferences. Females exhibited
      preferences for the red versions of male faces. It is proposed that male
      coloration might provide a cue to male quality.

PMID- 14667365
TI  - Evolutionary trade-offs between reproduction and dispersal in populations at
      expanding range boundaries.
AB  - During recent climate warming, some species have expanded their ranges northwards
      to keep track of climate changes. Evolutionary changes in dispersal have been
      demonstrated in these expanding populations and here we show that increased
      dispersal is associated with reduced investment in reproduction in populations of
      the speckled wood butterfly, Pararge aegeria. Evolutionary changes in flight
      versus reproduction will affect the pattern and rate of expansion at range
      boundaries in the future, and understanding these responses will be crucial for
      predicting the distribution of species in the future as climates continue to
      warm.

PMID- 14667366
TI  - The cause of 50 million-year-old colour.
AB  - Multilayer reflectors cause structural, 'metallic' colours in a diversity of
      animals today, yet are unknown in extinct species. We identify a multilayer
      reflector, causing structural colour, in a 50-million-year-old beetle from
      Messel, Germany. It is proposed that the original material of this reflector has
      been preserved, although this is not a precondition for determining original
      colours from ancient multilayer reflectors. Therefore, the potential exists to
      reveal the original colours of other (particularly arthropod) extinct species.

PMID- 14667367
TI  - Selection for parasitoid resistance alters mating success in Drosophila.
AB  - Parasite-mediated sexual selection is still a widely discussed hypothesis for the
      understanding of the evolution of secondary sex traits. Furthermore, it has
      sparked new fields such as ecological immunology. Despite this, most tests have
      been restricted to the manipulation of parasite loads. Here, we provide a new
      experimental approach, where resistance itself was manipulated. Parasitoid
      resistant Drosophila melanogaster males achieved a higher mating success compared
      with non-resistant conspecifics. The underlying mechanism however remains
      elusive.

PMID- 14667368
TI  - Plant species descriptions show signs of disease.
AB  - It is well known that diseases can greatly influence the morphology of plants,
      but often the incidence of disease is either too rare or the symptoms too obvious
      for the 'abnormalities' to cause confusion in systematics. However, we have
      recently come across several misinterpretations of disease-induced traits that
      may have been perpetuated into modern species inventories. Anther-smut disease
      (caused by the fungus Microbotryum violaceum) is common in many members of the
      Caryophyllaceae and related plant families. This disease causes anthers of
      infected plants to be filled with dark-violet fungal spores rather than pollen.
      Otherwise, their vegetative morphology is within the normal range of healthy
      plants. Here, we present the results of a herbarium survey showing that a number
      of type specimens (on which the species name and original description are based)
      in the genus Silene from Asia are diseased with anther smut. The primary visible
      disease symptom, namely the dark-violet anthers, is incorporated into the
      original species descriptions and some of these descriptions have persisted
      unchanged into modern floras. This raises the question of whether diseased type
      specimens have erroneously been given unique species names.

PMID- 14667369
TI  - Novel, posterior sensory organ in the trochophore larva of Phyllodoce maculata
      (Polychaeta).
AB  - A new posterior sensory organ (PSO), located at the dorsal midline of the
      hyposphere, is described by immunocytochemical detection of acetylated alpha
      tubulin and serotonin (5-HT) in a laser-scanning microscope, as well as three
      dimensional reconstructions after optical serial sectioning in the trochophore
      larva of the polychaete Phyllodoce maculata (Phyllodocidae). The unpaired PSO
      consists of five bipolar sensory cells, two of them being 5-HT immunopositive,
      which send axons to the cerebral ganglion and prototroch nerve. The dendrites of
      these cells project to the surface and bear one cilium each. A single neuronal
      fibre from the apical sensory organ innervates the PSO.

PMID- 14667370
TI  - The evolution of cursorial carnivores in the Tertiary: implications of elbow
      joint morphology.
AB  - The evolution of cursorial adaptations in Tertiary (65-1.65 Myr ago) carnivores
      has been a contentious issue. Most such studies have focused on the relationship
      between hind limb proportions and running speed. Here, we show morphometrically
      that in extant carnivores, the elbow joint has evolved in two distinct directions
      with mutually exclusive implications for locomotor ability and prey procurement.
      Some carnivores retain supinatory ability, allowing them to manipulate prey and
      other items with the forepaws. Such carnivores can become very large. Other
      carnivores lose the ability to supinate and become cursors. This allows for only
      moderate size increase. Modern carnivores above ca. 20 kg body mass are committed
      to one or other of these strategies. This threshold coincides with a postulated
      threshold in carnivore physiology. The biaxial pattern mostly follows
      phylogenetic lines, but a strong selective regime can override this signal, as
      shown by the extant cheetah. Oligocene (33.7-23.8 Myr ago) and early-middle
      Miocene (23.8-11.2 Myr ago) carnivores follow the same pattern, though in the
      Miocene the pattern is shifted towards larger body mass, which may be owing to
      the extraordinary richness of browsing ungulates at this time.

PMID- 14667371
TI  - Reduced oxygen at high altitude limits maximum size.
AB  - The trend towards large size in marine animals with latitude, and the existence
      of giant marine species in polar regions have long been recognized, but remained
      enigmatic until a recent study showed it to be an effect of increased oxygen
      availability in sea water of a low temperature. The effect was apparent in data
      from 12 sites worldwide because of variations in water oxygen content controlled
      by differences in temperature and salinity. Another major physical factor
      affecting oxygen content in aquatic environments is reduced pressure at high
      altitude. Suitable data from high-altitude sites are very scarce. However, an
      exceptionally rich crustacean collection, which remains largely undescribed, was
      obtained by the British 1937 expedition from Lake Titicaca on the border between
      Peru and Bolivia in the Andes at an altitude of 3809 m. We show that in Lake
      Titicaca the maximum length of amphipods is 2-4 times smaller than other low
      salinity sites (Caspian Sea and Lake Baikal).

PMID- 14667372
TI  - Evidence for Golgi bodies in proposed 'Golgi-lacking' lineages.
AB  - Golgi bodies are nearly ubiquitous in eukaryotic cells. The apparent lack of such
      structures in certain eukaryotic lineages might be taken to mean that these
      protists evolved prior to the acquisition of the Golgi, and it raises questions
      of how these organisms function in the absence of this crucial organelle. Here,
      we report gene sequences from five proposed 'Golgi-lacking' organisms (Giardia
      intestinalis, Spironucleus barkhanus, Entamoeba histolytica, Naegleria gruberi
      and Mastigamoeba balamuthi). BLAST and phylogenetic analyses show these genes to
      be homologous to those encoding components of the retromer, coatomer and adaptin
      complexes, all of which have Golgi-related functions in mammals and yeast. This
      is, to our knowledge, the first molecular evidence for Golgi bodies in two major
      eukaryotic lineages (the pelobionts and heteroloboseids). This substantiates the
      suggestion that there are no extant primitively 'Golgi-lacking' lineages, and
      that this apparatus was present in the last common eukaryotic ancestor, but has
      been altered beyond recognition several times.

PMID- 14667373
TI  - Infection increases the value of nuptial gifts, and hence male reproductive
      success, in the Hymenolepis diminuta-Tenebrio molitor association.
AB  - During copulation, male insects pass accessory gland components to the female
      with the spermatophore. These gifts can affect female reproductive behaviour,
      ovulation and oviposition. Here, we show that female mealworm beetles, Tenebrio
      molitor, mated with males infected with metacestodes of the rat tapeworm,
      Hymenolepis diminuta, produced significantly more offspring than those mated with
      uninfected males. There is a significant positive relationship between parasite
      intensity in the male and reproductive output in the female. Infection results in
      a significant increase in bean-shaped accessory gland (BAG) size. We suggest that
      infected males pass superior nuptial gifts to females and discuss the confounding
      effects of infection in male and female beetles upon overall fitness costs of
      infection for the host and the likelihood that the parasite is manipulating host
      investment in reproduction.

PMID- 14667374
TI  - Growth trades off with habitat specialization.
AB  - How differences in niche breadth evolve and are maintained remains largely
      unknown. The 'jack of all trades is master of none' model of resource
      specialization has been widely considered, but, to our knowledge, never before
      supported empirically. It invokes performance trade-offs associated with
      specialization. Specialists should outperform generalists on a subset of
      resources, but be unable to maintain high performance over a broader range of
      resources. By contrast, generalists should perform less well, on average, using a
      greater diversity of resources. We report such trade-offs among four coral goby
      species in the wild. Habitat specialists grew faster than generalists in one of
      two habitats. Average growth rates of generalists were less than that of
      specialists, but more consistent between habitats. Performance trade-offs
      associated with resource specialization could influence the evolution and
      maintenance of narrow niche breadth.

PMID- 14667375
TI  - Range limits and parasite prevalence in a freshwater snail.
AB  - Geographical range limits are thought to be set by species' physiological or
      ecological adaptation to abiotic factors, but the importance of biotic factors
      such as parasitism in determining range limits has not been well explored. In
      this study the prevalence of trematode parasitism in populations of a freshwater
      gastropod snail, Lymnaea stagnalis, increased sharply as this species approached
      its western UK range limit. The likelihood of trematode infection increased with
      snail size, but high prevalence at the range edge was not a result of
      interpopulation variation in snail size. Changes in population growth rates
      resulting from high rates of parasitism at the range edge could contribute to
      range limitation. The mechanism driving high rates of parasitism at the range
      edge is not clear, but changes in abiotic factors towards the range limit may
      influence snail life history and immune response to trematode infection,
      indirectly altering the prevalence of parasites in marginal host populations.

PMID- 14667376
TI  - How might individual honeybees measure massive volumes?
AB  - We suggest how individual honeybees might measure the large volumes of potential
      nest sites and propose a key experimental test for our model.

PMID- 14667377
TI  - Spontaneous male death during copulation in an orb-weaving spider.
AB  - Males of some cannibalistic species of spiders and insects appear to sacrifice
      themselves by allowing the female to eat them, and the adaptive significance of
      such drastic terminal reproductive investment has recently been demonstrated for
      a spider. Typically, the female has to kill the male, but it has been suggested
      that males of some species in the cannibalistic orb-weaving spider genus Argiope
      may die in copula without female 'collaboration'. Here, we provide the first
      experimental evidence to our knowledge of programmed sudden death after onset of
      copulation in males of the spider Argiope aurantia. Our observations reveal that
      males invariably die during the insertion of their second pedipalp, regardless of
      whether they mate with newly moulted, defenceless females or with older mature
      females that often attack them. We determined experimentally that the death of
      males is triggered immediately upon insertion of the second palp, when males
      become unresponsive, and heartbeat ceases within minutes of insertion. We discuss
      the possible adaptive significance of programmed death during copulation, and
      argue that male death has evolved in a context other than sexual cannibalism.

PMID- 14667378
TI  - The emergent properties of a dolphin social network.
AB  - Many complex networks, including human societies, the Internet, the World Wide
      Web and power grids, have surprising properties that allow vertices (individuals,
      nodes, Web pages, etc.) to be in close contact and information to be transferred
      quickly between them. Nothing is known of the emerging properties of animal
      societies, but it would be expected that similar trends would emerge from the
      topology of animal social networks. Despite its small size (64 individuals), the
      Doubtful Sound community of bottlenose dolphins has the same characteristics. The
      connectivity of individuals follows a complex distribution that has a scale-free
      power-law distribution for large k. In addition, the ability for two individuals
      to be in contact is unaffected by the random removal of individuals. The removal
      of individuals with many links to others does affect the length of the
      'information' path between two individuals, but, unlike other scale-free
      networks, it does not fragment the cohesion of the social network. These self
      organizing phenomena allow the network to remain united, even in the case of
      catastrophic death events.

PMID- 14667379
TI  - Extremely short lifespan in the annual fish Nothobranchius furzeri.
AB  - Evolutionary theories of senescence postulate that lifespan is determined by the
      age-dependent decrease in the effects of natural selection. Factors that
      influence survival and reproduction at early life stages have a larger impact on
      fitness than factors that influence later life stages. According to these views,
      selection for rapid sexual maturation and a steep age-dependent decrease in
      fitness drive the evolution of short lifespans. Here, we report on the survival
      trajectory of Nothobranchius furzeri (Pisces: Ciprinodontidae): a member of a
      group of annual species found in temporary bodies of water whose life expectancy
      in the wild is limited to a few months. We find that maximum survival of N.
      furzeri in the laboratory is less than 12 weeks. The temporal trajectory of
      survival shows an age-dependent increase in the mortality rate that is typical of
      organisms with defined lifespans. The lifespan of N. furzeri is exceptionally
      short for a vertebrate: owing to its small size and the possibility of
      propagation in captivity, N. furzeri could be used as a convenient model for
      ageing research.

PMID- 14667380
TI  - Is a decline in offspring quality a necessary consequence of maternal age?
AB  - Recent studies in two species of Drosophila have demonstrated a negative effect
      of parental age on offspring fitness, including a reduced hatch rate of eggs and
      larval-to-adult viability. This has led to a call to consider the decline of
      offspring quality as a function of parental age in theoretical considerations of
      the evolution of ageing. We have tested whether a decline in egg and larval
      quality of older mothers is a general feature of senescence by examining it in
      the cockroach Nauphoeta cinerea. We also tested whether maternal age affected the
      reproductive potential of daughters. Although maternal age at first reproduction
      profoundly affected maternal fitness, there was no difference in hatch rate or
      larval viability between the offspring of young and old mothers. Likewise, the
      reproductive potential of the daughters of young and old mothers was the same.
      Thus, while maternal age effects may be important aspects of ageing in some
      systems, the generality and overall importance for theories of ageing remain
      unclear.

PMID- 14667381
TI  - Sensory integration in the hydrodynamic world of rainbow trout.
AB  - Water movements, of both abiotic and biotic origin, provide a wealth of
      information for fishes. They detect these water movements by arrays of
      hydrodynamic sensors located on the surface of the body as superficial neuromasts
      and embedded in subdermal lateral line canals. Recently, the anatomical dichotomy
      between superficial and canal neuromasts has been matched by demonstrations of a
      corresponding functional dichotomy. Superficial neuromasts are sensitive to water
      flows over the surface of the fish and are the sub-modality that participates in
      orientation to water currents, a behaviour known as rheotaxis. The canal
      neuromasts are sensitive to water vibration and it is this sub-modality that
      determines the localization of artificial prey. Recently, however, it has been
      shown that the complex behaviour of natural prey capture in the dark requires
      input from both lateral line sensory submodalities and here we show that the
      ability of trout to hold station behind a stationary object in fast flowing water
      also requires integration of information from both sub-modalities.

PMID- 14667382
TI  - Removing the confounding effect of habitat specialization reveals the stabilizing
      contribution of diversity to species variability.
AB  - Earlier studies have found that diversity, S, stabilizes the relative variability
      of combined biomass or abundance of species making up a community. However, the
      effect of S on variability of constituent species has been elusive. We
      hypothesize that the proportion of specialists increases with S and, because
      specialists are more variable, this shift in composition will mask the
      stabilizing effect of S on populations of species making up a community. The test
      uses data on variability and ecological specialization of species in 49 natural
      rock pool invertebrate communities. Initial analyses produced inconclusive
      results similar to earlier studies. However, when variability owing to species'
      specialization was factored out, S reduced species' abundance variability,
      although not in all communities. Our study explains why the stabilizing effect of
      diversity on populations has not been found earlier.

PMID- 14667383
TI  - Characterization of methanogenic and methanotrophic assemblages in landfill
      samples.
AB  - A greater understanding of the tightly linked trophic groups of anaerobic and
      aerobic bacteria residing in municipal solid waste landfills will increase our
      ability to control methane emissions and pollutant fate in these environments. To
      this end, we characterized the composition of methanogenic and methanotrophic
      bacteria in samples taken from two regions of a municipal solid waste landfill
      that varied in age. A method combining polymerase chain reaction amplification,
      restriction fragment length polymorphism analysis and phylogenetic analysis was
      used for this purpose. 16S rDNA sequence analysis revealed a rich assemblage of
      methanogens in both samples, including acetoclasts, H2/CO2-users and formate
      users in the newer samples and H2/CO2-users and formate-users in the older
      samples, with closely related genera including Methanoculleus, Methanofollis,
      Methanosaeta and Methanosarcina. Fewer phylotypes of type 1 methanotrophs were
      observed relative to type 2 methanotrophs. Most type 1 sequences clustered within
      a clade related to Methylobacter, whereas type 2 sequences were broadly
      distributed among clades associated with Methylocystis and Methylosinus species.
      This genetic characterization tool promises rapid screening of landfill samples
      for genotypes and, therefore, degradation potentials.

PMID- 14667384
TI  - Unusual gut contents in a Cretaceous ichthyosaur.
AB  - Despite ichthyosaurs being one of the most extensively studied Mesozoic marine
      reptile groups, there is little documented direct evidence of dietary habits in
      most taxa. Here, we report the discovery of hatchling-sized marine protostegid
      turtle remains and an enantiornithine bird (in association with actinopterygian
      fish and phosphatic nodules) within the body cavity of a gravid female
      ichthyosaur (Platypterygius longmani) from the Lower Cretaceous of Australia;
      this is the first evidence, to our knowledge, of feeding by ichthyosaurs upon
      both turtles and birds. The exceptionally preserved gut contents show little
      evidence of digestion, suggesting consumption shortly before the ichthyosaur's
      death. Poor swimming ability may have made hatchling turtles easy prey that could
      have been either swallowed whole or processed by shake feeding. Ingestion of bird
      remains probably occurred through scavenging. Opportunistic feeding on
      vertebrates is at odds with existing interpretations of dietary habits in
      Cretaceous ichthyosaurs, which favour predation primarily upon cephalopods. Such
      specialization is considered a contributing factor in the group's ultimate
      extinction. However, the evidence here that at least some forms were able to use
      a wide range of available food types suggests that the decline of ichthyosaurs in
      the mid-Cretaceous may be linked to other factors such as competition with
      ecologically analogous pursuit predators.

PMID- 14667385
TI  - Facultative symbionts are associated with host plant specialization in pea aphid
      populations.
AB  - The pea aphid, Acyrthosiphon pisum, shows significant reproductive isolation and
      host plant specialization between populations on alfalfa and clover in New York.
      We examine whether specialization is seen in pea aphids in California, and
      whether fitness on alternative host plants is associated with the presence of
      bacterial symbionts. We measured the fitness of alfalfa- and clover-derived
      aphids on both types of plants and found no evidence for specialization when all
      aphid lineages were considered simultaneously. We then screened all aphids for
      the presence of four facultative bacterial symbionts: PAR, PASS, PABS and PAUS.
      Aphids with PAUS were host-plant specialized, having twice as many offspring as
      other aphids on clover, and dying on alfalfa. Other aphids showed no evidence of
      specialization. Additionally, aphids with PABS had 50% more offspring than aphids
      with PASS when on alfalfa. Thus, specialist and generalist aphid lineages
      coexist, and specialization is symbiont associated. Further work will resolve
      whether PAUS is directly responsible for this variation in fitness or whether
      PAUS is incidentally associated with host-plant specialized aphid lineages.

PMID- 14667386
TI  - Parasite removal and its impact on litter size and body condition in Columbian
      ground squirrels (Spermophilus columbianus).
AB  - The current interest in studies of parasite-host relationships is focusing on the
      impact of parasites on mate choice, sexual selection and individual fitness.
      While most studies have been done on birds and fishes, little is known about the
      interactions between parasites and reproductive success in mammals. In this
      study, I experimentally removed ectoparasites (mainly fleas) from some female
      Columbian ground squirrels using a commercially available powder, whereas other
      squirrels were left untreated as controls. The anti-parasite treatment led to an
      increase in female body condition during lactation and at weaning and an increase
      in litter size. The increase of body mass in treated females between birth of the
      young and weaning is also different from observations done over 8 years in the
      same population, where untreated females usually lost mass. In close to 400
      litters from untreated females in the same area, only 2% had litter sizes as big
      as the treated females. I conclude that ectoparasites can have a profound impact
      not only on individuals but probably on the dynamics of the whole population.

PMID- 14667387
TI  - Subtle manipulation of egg sex ratio in birds.
AB  - Mothers are predicted to overproduce male or female eggs when the relative
      fitness gains from one sex are higher and outweigh the costs of manipulation.
      However, in birds such biases are often difficult to distinguish from
      differential embryo or chick mortality. Using a molecular technique to identify
      the sex of early embryos, we aim to determine the effect of maternal nutrition on
      zebra finch (Taeniopygia guttata) egg sex ratios after 2 days of incubation,
      which is as close to conception as is currently possible. We found no overall
      bias in the sex ratio of eggs laid and sex did not differ with relative laying
      order under any diet regime. However, mothers on a low-quality diet did produce a
      female bias in small clutches and a slight male bias in large clutches. On a high
      quality diet, mothers produced a male bias in small clutches and a female bias in
      large clutches. Those on a standard diet produced a roughly even sex ratio,
      irrespective of clutch size. These observed biases in egg sex are partly in line
      with predictions that, in this species, daughters suffer disproportionately from
      poor rearing conditions. Thus, when relatively malnourished, mothers should only
      rear daughters in small broods and vice versa. Sex-ratio patterns in this species
      therefore appear to be subtle.

PMID- 14667388
TI  - Immune response is energetically costly in white cabbage butterfly pupae.
AB  - Parasite-driven coevolution has led hosts to develop a complicated and
      potentially costly defence machinery, consisting mainly of the immune system.
      Despite the evidence for the trade-offs between immune function and life-history
      traits, it is still obscure how the costs of using and maintaining the immune
      function are paid. We tested whether immune challenge is energetically costly for
      white cabbage butterfly (Pieris brassicae L.) diapausing pupa. Individuals
      challenged with nylon implant raised their standard metabolic rate nearly 8%
      compared to the controls. Hence, costs of activation of immune system in insect
      pupa can be expressed in energetic currency.

PMID- 14667389
TI  - Efficient utilization of very dilute aquatic sperm: sperm competition may be more
      likely than sperm limitation when eggs are retained.
AB  - Fertilization success may be severely limited in marine invertebrates that spawn
      both male and female gametes. In a diverse group of aquatic organisms only sperm
      are released, with sperm-egg fusion occurring at the mother. Here, we report
      fertilization kinetics data for two such 'brooding' or 'spermcast' species-
      representing each major clade of the animal kingdom. High levels of fertilization
      were achieved at sperm concentrations of two or three orders of magnitude lower
      than is common with broadcast spawning species. At a concentration of 100 sperm
      ml(-1), fertilization rates of a bryozoan and colonial ascidian were near
      maximum, whereas most broadcast spawners would have displayed near complete
      reproductive failure. A further experiment looked at the rate of uptake of sperm
      under natural conditions. Results suggested that sperm released at ca. 0.9 m from
      an acting female could be collected at a rate of 3-12 times greater than the
      minimum required simply to avoid sperm limitation. Thus, evolutionary pressures
      on gametic and other reproductive characteristics of many species that release
      sperm but retain eggs may be quite different from those of broadcast spawners and
      may confer on the former an enhanced scope for sperm competition and female
      choice.

PMID- 14667390
TI  - Effects of sperm on female longevity in the bumble-bee Bombus terrestris L.
AB  - The male ejaculate, particularly the accessory gland products, has been shown to
      affect female survival (as is best understood in Drosophila melanogaster). So
      far, these findings have primarily been discussed in the context of a sexual
      conflict and multiple mating. Here, we show that in the bumble-bee Bombus
      terrestris, male genotype influences female longevity even though B. terrestris
      generally is a singly mated species and male and female interests may thus be
      more convergent. In addition, the effect could not be owing to accessory gland
      products, as we artificially inseminated the queens with the content of the
      accessory testes only.

PMID- 14667391
TI  - Marine protected areas in 'nonlinear' ecosystems.
AB  - The very large changes observed within marine communities, owing to excessive
      harvesting, have been attributed to switches between alternative stable states.
      Correspondingly large reductions in overall fishing effort are usually difficult
      to implement. For such 'nonlinear' ecosystems, introducing large marine protected
      areas, with low to zero harvesting, but without reduction in overall fishing
      effort, can give a marked increase in total yield of the depleted stocks. These
      increases, however, are still less than can be achieved by reducing fishing
      effort.

PMID- 14667392
TI  - Arizonasaurus and its implications for archosaur divergence.
AB  - The Moenkopi Formation has yielded partial and isolated remains of important
      archosaurs including rauisuchian skull fragments and isolated poposaur centra and
      pelvic girdle elements. A recently discovered skeleton referable to Arizonasaurus
      babbitti shows that most of these archosaurian remains belong to one taxon.
      Characteristics of the skeleton of Arizonasaurus show that it belongs to a poorly
      known group of Middle Triassic (240-230 Myr ago) archosaurs called the
      ctenosauriscids, and that ctenosauriscids are or are closely related to
      poposaurs. Furthermore, many characteristics of Arizonasaurus provide evidence
      that poposaurids and ctenosauriscids are derived rauisuchians. The presence of a
      poposaurid in the early Middle Triassic suggests that the divergence of birds and
      crocodiles occurred earlier than previously thought. Middle Triassic
      ctenosauriscids also allow the correlation of Triassic faunas in Europe, Asia,
      North America and Africa. The Moenkopi Formation fauna represents a transitional
      fauna between Early and Late Triassic faunas.

PMID- 14667393
TI  - Sapayoa aenigma: a New World representative of 'Old World suboscines'.
AB  - Passerine birds are very plastic in their adaptations, which has made it
      difficult to define phylogenetic lineages and correctly allocate all species to
      these. Sapayoa aenigma, a member of the large group of New World flycatchers, has
      been difficult to place, and DNA-DNA hybridization experiments have indicated
      that it may have been misplaced. This is confirmed here, as base sequencing of
      two nuclear genes places it as a deep branch in the group of broadbills and
      pittas of the Old World tropics. The peculiar distribution of this lineage may be
      best explained in terms of a Gondwanic and Late Cretaceous origin of the
      passerine birds, as this particular lineage dispersed from the Antarctic
      landmass, reaching the Old World tropics via the drifting Indian plate, and South
      America via the West Antarctic Peninsula.

PMID- 14667394
TI  - Cleaner wrasse prefer client mucus: support for partner control mechanisms in
      cleaning interactions.
AB  - Recent studies on cleaning behaviour suggest that there are conflicts between
      cleaners and their clients over what cleaners eat. The diet of cleaners usually
      contains ectoparasites and some client tissue. It is unclear, however, whether
      cleaners prefer client tissue over ectoparasites or whether they include client
      tissue in their diet only when searching for parasites alone is not profitable.
      To distinguish between these two hypotheses, we trained cleaner fish Labroides
      dimidiatus to feed from plates and offered them client mucus from the parrotfish
      Chlorurus sordidus, parasitic monogenean flatworms, parasitic gnathiid isopods
      and boiled flour glue as a control. We found that cleaners ate more mucus and
      monogeneans than gnathiids, with gnathiids eaten slightly more often than the
      control substance. Because gnathiids are the most abundant ectoparasites, our
      results suggest a potential for conflict between cleaners and clients over what
      the cleaner should eat, and support studies emphasizing the importance of partner
      control in keeping cleaning interactions mutualistic.

PMID- 14667395
TI  - Geographical variation and sexual dimorphism of phenoloxidase levels in Japanese
      beetles (Popillia japonica).
AB  - Phenoloxidase (PO) production can be used as an indicator of pathogen defence in
      insects. The geographical mosaic of coevolution implies that traits associated
      with pathogen defence will vary across a geographical range. Bateman's principle
      implies that the benefit of increased defence levels is greater for females than
      males. To test both of these hypotheses, we sampled four populations of Japanese
      beetles, Popillia japonica, across Vermont: two were from locations using
      biological pest control, and two locations did not use biocontrol. We quantified
      defence levels (PO) and parasite resistance in males and females from each
      population. Populations from areas with biocontrol exhibited greater PO
      production, females produced more PO, populations with higher levels of PO
      suffered less mortality from pathogen exposure, and PO levels positively
      correlate with increased mortality in the absence of parasitism. Results support
      the geographical mosaic of coevolution and the implications of Bateman's
      principle.

PMID- 14667396
TI  - Sexual selection and individual genetic diversity in a songbird.
AB  - Here, we report for the first time, to our knowledge, a strong correlation
      between a measure of individual genetic diversity and song complexity, a sexually
      selected male trait in sedge warblers, Acrocephalus schoenobaenus. We also find
      that females prefer to mate with males who will maximize this diversity in
      individual progeny. The genetic diversity of each offspring is further increased
      by means of nonrandom fertilization, as we also show that the fertilizing sperm
      contains a haplotype more genetically distant to that of the egg than expected by
      chance. These findings suggest that species' mating preferences may be subject to
      fine tuning aimed at increasing offspring viability through increased genetic
      diversity. This includes external and internal mechanisms of selection, even
      within the ejaculate of a single male.

PMID- 14667397
TI  - Does female mortality drive male semelparity in dasyurid marsupials?
AB  - In some members of the marsupial families Didelphidae and Dasyuridae, males are
      semelparous, that is, they live for only one mating season. Semelparity is
      proposed to be the result of the high energy demands of competing for matings
      with many females during a short breeding season. We argue that high adult female
      mortality rates between mating and weaning of the offspring selects for a
      'bethedging' mating strategy in males. We tested this hypothesis in a well
      studied field population of Antechinus agilis by estimating the number of females
      a male needs to mate with in order to have a high chance of siring at least one
      offspring that survives to the next breeding season. Our hypothesis predicts that
      species in which males are semelparous should have higher female mortality rates
      than species in which males are iteroparous. The limited available data for
      dasyurid marsupials support this prediction.

PMID- 14667398
TI  - Major histocompatibility complex and mate choice in sand lizards.
AB  - In mice and man, females prefer males with a major histocompatibility complex
      (MHC) genotype different to their own. We tested whether this phenomenon also
      occurs in the Swedish sand lizard (Lacerta agilis). Females in a laboratory
      experiment preferred to associate with odour samples obtained from more distantly
      related males at the MHC class 1 loci. Data on free-ranging lizards suggest that
      associations between males and females are nonrandom with respect to MHC
      genotype. However, male spatial distribution and mobility during the mating
      season suggest that the non-random pairing process in the wild may also be driven
      by corresponding genetic benefits to males pairing with less related females.

PMID- 14667400
TI  - Cellular development.

PMID- 14667401
TI  - On best behavior: cadherins drive slow muscle to their limits.

PMID- 14667402
TI  - Sensing membrane curvature.

PMID- 14667403
TI  - The secret life of Smoothened.

PMID- 14667404
TI  - Auxin transport: the fountain of life in plants?

PMID- 14667405
TI  - Online with stem cells.

PMID- 14667406
TI  - Drosophila nonmuscle myosin II promotes the asymmetric segregation of cell fate
      determinants by cortical exclusion rather than active transport.
AB  - Cell fate diversity can be achieved through the asymmetric segregation of cell
      fate determinants. In the Drosophila embryo, neuroblasts divide asymmetrically
      and in a stem cell fashion. The determinants Prospero and Numb localize in a
      basal crescent and are partitioned from neuroblasts to their daughters (GMCs).
      Here we show that nonmuscle myosin II regulates asymmetric cell division by an
      unexpected mechanism, excluding determinants from the apical cortex. Myosin II is
      activated by Rho kinase and restricted to the apical cortex by the tumor
      suppressor Lethal (2) giant larvae. During prophase and metaphase, myosin II
      prevents determinants from localizing apically. At anaphase and telophase, myosin
      II moves to the cleavage furrow and appears to "push" rather than carry
      determinants into the GMC. Therefore, the movement of myosin II to the
      contractile ring not only initiates cytokinesis but also completes the
      partitioning of cell fate determinants from the neuroblast to its daughter.

PMID- 14667407
TI  - The Drosophila cell survival gene discs lost encodes a cytoplasmic Codanin-1-like
      protein, not a homolog of tight junction PDZ protein Patj.
AB  - The Drosophila gene discs lost (dlt) has been reported to encode a homolog of the
      vertebrate tight junction PDZ protein Patj, and was thought to play a role in
      cell polarity. Using rescue experiments and sequence analyses, we show that dlt
      mutations disrupt the Drosophila Codanin-1 homolog, a cytoplasmic protein, and
      not the PDZ protein. Mutations in human Codanin-1 are associated with congenital
      dyserythropoietic anemia type I (CDA I). In Drosophila, the genomic organization
      of dlt is unusual. dlt shares its first untranslated exon with alpha-spectrin,
      and both genes are coexpressed throughout development. We show that dlt is not
      required for cell polarity but is needed for cell survival and cell cycle
      progression. Finally, we present evidence that the PDZ protein previously thought
      to be encoded by dlt is not required for viability. We propose to rename this PDZ
      protein after its vertebrate homolog, Patj (Pals-associated tight junction
      protein).

PMID- 14667408
TI  - CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of
      Aurora-B at inner centromeres and for kinetochore function.
AB  - The Aurora (Ipl1)-related kinases are universal regulators of mitosis. We now
      show that Aurora-A, in addition to Aurora-B, regulates kinetochore function in
      human cells. A two-hybrid screen identified the kinetochore component CENP-A as a
      protein that interacts with Aurora-A. Aurora-A phosphorylated CENP-A in vitro on
      Ser-7, a residue also known to be targeted by Aurora-B. Depletion of Aurora-A or
      Aurora-B by RNA interference revealed that CENP-A is initially phosphorylated in
      prophase in a manner dependent on Aurora-A, and that this reaction appears to be
      required for the subsequent Aurora-B-dependent phosphorylation of CENP-A as well
      as for the restriction of Aurora-B to the inner centromere in prometaphase.
      Prevention of CENP-A phosphorylation also led to chromosome misalignment during
      mitosis as a result of a defect in kinetochore attachment to microtubules. Our
      observations suggest that phosphorylation of CENP-A on Ser-7 by Aurora-A in
      prophase is essential for kinetochore function.

PMID- 14667409
TI  - Cadherin-mediated differential cell adhesion controls slow muscle cell migration
      in the developing zebrafish myotome.
AB  - Slow-twitch muscle fibers of the zebrafish myotome undergo a unique set of
      morphogenetic cell movements. During embryogenesis, slow-twitch muscle derives
      from the adaxial cells, a layer of paraxial mesoderm that differentiates medially
      within the myotome, immediately adjacent to the notochord. Subsequently, slow
      twitch muscle cells migrate through the entire myotome, coming to lie at its most
      lateral surface. Here we examine the cellular and molecular basis for slow-twitch
      muscle cell migration. We show that slow-twitch muscle cell morphogenesis is
      marked by behaviors typical of cells influenced by differential cell adhesion.
      Dynamic and reciprocal waves of N-cadherin and M-cadherin expression within the
      myotome, which correlate precisely with cell migration, generate differential
      adhesive environments that drive slow-twitch muscle cell migration through the
      myotome. Removing or altering the expression of either protein within the myotome
      perturbs migration. These results provide a definitive example of homophilic cell
      adhesion shaping cellular behavior during vertebrate development.

PMID- 14667411
TI  - Imprinting of the MEA Polycomb gene is controlled by antagonism between MET1
      methyltransferase and DME glycosylase.
AB  - The MEA Polycomb gene is imprinted in the Arabidopsis endosperm. DME DNA
      glycosylase activates maternal MEA allele expression in the central cell of the
      female gametophyte, the progenitor of the endosperm. Maternal mutant dme or mea
      alleles result in seed abortion. We identified mutations that suppress dme seed
      abortion and found that they reside in the MET1 methyltransferase gene, which
      maintains cytosine methylation. Seeds with maternal dme and met1 alleles survive,
      indicating that suppression occurs in the female gametophyte. Suppression
      requires a maternal wild-type MEA allele, suggesting that MET1 functions upstream
      of, or at, MEA. DME activates whereas MET1 suppresses maternal MEA::GFP allele
      expression in the central cell. MET1 is required for DNA methylation of three
      regions in the MEA promoter in seeds. Our data suggest that imprinting is
      controlled in the female gametophyte by antagonism between the two DNA-modifying
      enzymes, MET1 methyltransferase and DME DNA glycosylase.

PMID- 14667410
TI  - Isl1 identifies a cardiac progenitor population that proliferates prior to
      differentiation and contributes a majority of cells to the heart.
AB  - Hearts of mice lacking Isl1, a LIM homeodomain transcription factor, are
      completely missing the outflow tract, right ventricle, and much of the atria.
      isl1 expression and lineage tracing of isl1-expressing progenitors demonstrate
      that Isl1 is a marker for a distinct population of undifferentiated cardiac
      progenitors that give rise to the cardiac segments missing in isl1 mutants. Isl1
      function is required for these progenitors to contribute to the heart. In isl1
      mutants, isl1-expressing progenitors are progressively reduced in number, and FGF
      and BMP growth factors are downregulated. Our studies define two sets of
      cardiogenic precursors, one of which expresses and requires Isl1 and the other of
      which does not. Our results have implications for the development of specific
      cardiac lineages, left-right asymmetry, cardiac evolution, and isolation of
      cardiac progenitor cells.

PMID- 14667413
TI  - The importance of genetic recombination for fidelity of chromosome pairing in
      meiosis.
AB  - In budding yeast, absence of the Hop2 protein leads to extensive synaptonemal
      complex (SC) formation between nonhomologous chromosomes, suggesting a crucial
      role for Hop2 in the proper alignment of homologous chromosomes during meiotic
      prophase. Genetic analysis indicates that Hop2 acts in the same pathway as the
      Rad51 and Dmc1 proteins, two homologs of E. coli RecA. Thus, the hop2 mutant
      phenotype demonstrates the importance of the recombination machinery in promoting
      accurate chromosome pairing. We propose that the Dmc1/Rad51 recombinases require
      Hop2 to distinguish homologous from nonhomologous sequences during the homology
      search process. Thus, when Hop2 is absent, interactions between nonhomologous
      sequences become inappropriately stabilized and can initiate SC formation.
      Overexpression of RAD51 largely suppresses the meiotic defects of the dmc1 and
      hop2 mutants. We conclude that Rad51 is capable of carrying out a homology search
      independently, whereas Dmc1 requires additional factors such as Hop2.

PMID- 14667412
TI  - Knockdown of zebrafish Fancd2 causes developmental abnormalities via p53
      dependent apoptosis.
AB  - Mechanisms underlying the multiple developmental defects observed in Fanconi
      anemia (FA) patients are not well defined. We have identified the zebrafish
      homolog of human FANCD2, which encodes a nuclear effector protein that is
      monoubiquitinated in response to DNA damage, targeting it to nuclear foci where
      it preserves chromosomal integrity. Fancd2-deficient zebrafish embryos develop
      defects similar to those found in children with FA, including shortened body
      length, microcephaly, and microophthalmia, which are due to extensive cellular
      apoptosis. Developmental defects and increased apoptosis in Fancd2-deficient
      zebrafish were corrected by injection of human FANCD2 or zebrafish bcl2 mRNA, or
      by knockdown of p53, indicating that in the absence of Fancd2, developing tissues
      spontaneously undergo p53-dependent apoptosis. Thus, Fancd2 is essential during
      embryogenesis to prevent inappropriate apoptosis in neural cells and other
      tissues undergoing high levels of proliferative expansion, implicating this
      mechanism in the congenital abnormalities observed in human infants with FA.

PMID- 14667414
TI  - The Hop2 protein has a direct role in promoting interhomolog interactions during
      mouse meiosis.
AB  - The S. cerevisiae Hop2 protein and its fission yeast homolog Meu13 are required
      for proper homologous chromosome pairing and recombination during meiosis. The
      mechanism of this requirement is, however, not understood. The previous studies
      in Saccharomyces suggested that Hop2 is a guardian of meiotic chromosome synapsis
      with the ability to prevent or resolve deleterious associations between
      nonhomologous chromosomes. We have generated a Hop2 knockout mouse that shows
      profound meiotic defects with a distinct and novel phenotype. Hop2(-/-)
      spermatocytes arrest at the stage of pachytene-like chromosome condensation.
      Axial elements are fully developed, but synapsis of any kind is very limited.
      Immunofluorescence analysis of meiotic chromosome spreads indicates that while
      meiotic double-stranded breaks are formed and processed in the Hop2 knockout,
      they fail to be repaired. In aggregate, the Hop2 phenotype is consistent with a
      direct role for the mouse Hop2 protein in promoting homologous chromosome
      synapsis.

PMID- 14667415
TI  - A Tcf4-positive mesodermal population provides a prepattern for vertebrate limb
      muscle patterning.
AB  - Nai;ve myogenic cells migrate from the somites into the developing vertebrate
      limb, where they simultaneously differentiate into myotubes and form distinct
      anatomical muscles. Limb signals have been hypothesized to direct the pattern of
      muscles formed, but the molecular nature of these signals and the identity of the
      cells that produce them have remained unclear. We have identified a population of
      lateral plate-derived limb mesodermal cells in both chick and mouse that
      expresses the transcription factor Tcf4 in a muscle-specific pattern
      independently of the muscle cells themselves. Functional experiments in the chick
      demonstrate that TCF4 and the Wnt-beta-catenin pathway in these limb mesodermal
      cells are critical for muscle patterning. We propose that Tcf4-expressing cells
      establish a prepattern in the limb mesoderm that determines the sites of myogenic
      differentiation and thus establishes the basic pattern of limb muscles.

PMID- 14667416
TI  - Spatial regulation of developmental signaling by a serpin.
AB  - An extracellular serine protease cascade generates the ligand that activates the
      Toll signaling pathway to establish dorsoventral polarity in the Drosophila
      embryo. We show here that this cascade is regulated by a serpin-type serine
      protease inhibitor, which plays an essential role in confining Toll signaling to
      the ventral side of the embryo. This role is strikingly analogous to the function
      of the mammalian serpin antithrombin in localizing the blood-clotting cascade,
      suggesting that serpin inhibition of protease activity may be a general mechanism
      for achieving spatial control in diverse biological processes.

PMID- 14667417
TI  - Self-generated alcohol outcomes in 8th and 10th graders: exposure to vicarious
      sources of alcohol information.
AB  - The perceived positive and negative outcomes of alcohol use were studied in a
      sample of normal 8th and 10th grade students. Participants' responses provided
      associative frequency norms valuable for future research. Regression analyses
      showed (1) none of the individual-difference variables (alcohol use, exposure to
      vicarious sources of alcohol information, such as televised advertising, and
      demographics) predicted self-generated responses, and (2) alcohol use and first
      hand observation of others' drinking did predict the valence respondents assigned
      to the outcomes. Results support and extend the findings of Stacy, Galaif,
      Sussman, and Dent [Psychology of Addictive Behaviors 10(1) 1996 18], wherein self
      generated drug use outcomes appeared to be available in memory regardless of
      previous drug use or other individual differences.

PMID- 14667418
TI  - Beyond modeling: parenting practices, parental smoking history, and adolescent
      cigarette smoking.
AB  - This study explored parental beliefs and behaviors designed to convey an
      antismoking message across levels of self-reported parent and adolescent smoking
      behavior. Parental self-efficacy, beliefs about smoking, the family relationship,
      antismoking messages, reactions to smoking, and household smoking rules were
      explored. Participants were 345 6th, 8th, and 10th graders (50% female; 93%
      White) and their parents (86% mothers). Beliefs about smoking, parental efficacy,
      and rules varied across levels of both parental and adolescent smoking. Parents
      with a history of smoking and parents of adolescents who had tried smoking were
      less efficacious, held weaker antismoking beliefs, and less often reported
      household smoking rules. Overall, examining parental behavior across levels of
      both parent and youth smoking is important. Similarly, parental efficacy, not
      previously studied in relation to parenting about smoking, may be important to
      target in future interventions.

PMID- 14667419
TI  - fMRI BOLD response to alcohol stimuli in alcohol dependent young women.
AB  - BACKGROUND: Cue reactivity in alcohol dependent adults has revealed autonomic,
      cognitive, and neural responses to alcohol-related stimuli that differ from those
      of nonabusers. Cue reactivity and craving responses have not been studied in
      youth. METHOD: Alcohol-dependent young women (n=8) and female light social
      drinkers (n=9) ages 18-24 were administered an alcohol cue reactivity task during
      functional magnetic resonance imaging (fMRI) to examine brain response to alcohol
      related words. RESULTS: Alcohol dependent young women demonstrated significantly
      more blood oxygen level dependent (BOLD) response than nonabusers during alcohol
      word presentation trials relative to neutral word trials in subcallosal, anterior
      cingulate, left prefrontal, and bilateral insular regions (P<.025). However,
      controls showed greater response to alcohol words in some right hemisphere
      cortical regions. Increased craving after cue exposure correlated with increased
      subcallosal cortex BOLD response to alcohol cues (r=.87) among alcohol dependent
      subjects. CONCLUSIONS: This pilot study corroborates previous reports of
      increased limbic and frontal response to substance cues and extends these
      findings to young alcohol dependent women. This limbic reaction may underlie the
      elevated physiological response and altered cognitive reactions to alcohol
      stimuli that are observed in alcohol dependent individuals.

PMID- 14667420
TI  - A comparison of four self-report smoking cessation outcome measures.
AB  - Interventions for smoking cessation have been developed by researchers in a
      number of distinct disciplines. As a result, a variety of different outcome
      measures have been developed and employed. This paper will report an analysis
      that compares four smoking cessation outcome measures on data gathered from three
      population-based studies: (1) 24-hour point prevalence abstinence, (2) 7-day
      point prevalence abstinence, (3) 30-day prolonged abstinence, and (4) 6-month
      prolonged abstinence. The three studies provided a total of 41 mean estimates for
      the first three measures but only 28 mean estimates for the 6-month prolonged
      abstinence measure. The data demonstrate an extremely high relationship between
      all four measures. The first three measures (24-hour point prevalence, 7-day
      point prevalence, and 30-day prolonged abstinence) all correlated in excess of.98
      with each other. The only measure that did not demonstrate the same degree of
      almost perfect equivalence was 6-month prolonged abstinence, but even here the
      lowest correlation with the other three measures was.82. For practical purposes,
      the first three measures will result in the same conclusions when used as outcome
      measures in smoking cessation studies.

PMID- 14667421
TI  - Covariation in addictive behaviours: a study of addictive orientations using the
      Shorter PROMIS Questionnaire.
AB  - Previous research has suggested that different addictive behaviours are linked,
      such that decreases in one may lead to compensatory increases in another, or even
      that one addiction may lead to another. Such views on "cross addiction" are
      encouraged by the prevailing tendency amongst researchers from very different
      theoretical backgrounds to view different addictions as serving a common
      function, such as mood alteration, or the "management of hedonic tone." Previous
      studies have suggested that different addictions may usefully be grouped
      according to how they covary. The present study, using factor and cluster
      analyses, confirms the importance of a division between "hedonistic" and
      "nurturant" addictions, but with the need for further subdivisions within those
      categories. Hedonism comprises a "drug use" factor and an "interpersonal
      dominance" factor. Nurturance comprises both "self-regarding" and "other
      regarding" factors. Theoretically, the results suggest that different addictions
      illustrate contrasting techniques of interpersonal manipulation. Clinically, the
      results indicate the drawbacks of addressing addictive behaviours singly, and the
      potential importance of addictive orientations in treatment, and relapse
      prevention.

PMID- 14667422
TI  - Node-link-mapping-enhanced group treatment for pathological gambling.
AB  - Two experiments evaluated a group treatment for pathological gambling that used
      node-link mapping techniques to enhance treatment effectiveness. In Experiment 1,
      13 (8 female) pathological gamblers were randomly assigned to either a mapping
      group (n=4), a nonmapping group (n=4), or a wait-list control group (n=5). The
      treatments were conducted by Master's level counselors during 90-min sessions
      conducted twice per week for 8 weeks. Participants were assessed pre- and post-8
      weeks and then 6 months later on Diagnostic and Statistical Manual of Mental
      Disorders 4th ed. (DSM-IV) pathological gambling criteria, three self-ratings of
      control of gambling, gambling expenditure, and gambling bout duration. Experiment
      2 replicated the mapping (n=9; 8 female) and wait-list (n=10; 8 female)
      conditions of Experiment 1 and expanded the dependent measures to include
      assessment of changes in cooccurring depression and anxiety. The node-link
      mapping-enhanced group treatment produced improvements in more of the dependent
      measures of pathological gambling than treatment without maps (Experiment 1) or
      an equivalent-length waiting period (Experiments 1 and 2). It also produced
      larger decreases in cooccurring depression and anxiety than an equivalent-length
      waiting period (Experiment 2). The results are consistent with previous treatment
      research with substance abusers.

PMID- 14667423
TI  - Methamphetamine use behaviors and gender differences.
AB  - This analysis describes methamphetamine (MA) use behaviors in a broad cross
      section of (N=350) former clients from a large publicly funded treatment system
      and examines differences between males and females in drug use history, MA
      initiation and motivators, MA-related problems, acquisition, distribution,
      manufacture, and treatment characteristics. Results show polydrug use, prolonged
      MA use before treatment, initiation primarily through friends, common sensation
      seeking motivators (to have fun, get high, and experiment), numerous problems
      related to MA use (including paranoia, violent behavior, hallucinations,
      financial problems, and legal and work problems), and a majority who have sold
      MA. Gender differences appear in selected aspects of motivators and routes of
      initiation, access to MA, use patterns, and MA-related problems. Such description
      of behaviors and gender differences can provide a basis for development of
      treatment strategies and points of departure for future research.

PMID- 14667424
TI  - Cigarette smoking in a student sample: neurocognitive and clinical correlates.
AB  - Why do adolescents begin to smoke in the face of profound health risks and
      aggressive antismoking campaigns? The present study tested predictions based on
      two theoretical models of tobacco use in young adults: (1) the self-medication
      model; and (2) the orbitofrontal/disinhibition model. Investigators speculated
      that a significant number of smokers were self-medicating since nicotine
      possesses mood-elevating and hedonic properties. The self-medication model
      predicts that smokers will demonstrate increased rates of psychopathology
      relative to nonsmokers. Similarly, researchers have suggested that individuals
      with attention-deficit/hyperactivity disorder (ADHD) employ nicotine to enhance
      cognitive function. The ADHD/self-medication model predicts that smokers will
      perform poorly on tests of executive function and report a greater number of ADHD
      symptoms. A considerable body of research indicates that tobacco use is
      associated with several related personality traits including extraversion,
      impulsivity, risk taking, sensation seeking, novelty seeking, and antisocial
      personality features. Antisocial behavior and related personality traits as well
      as tobacco use may reflect, in part, a failure to effectively employ reward and
      punishment cues to guide behavior. This failure may reflect orbitofrontal
      dysfunction. The orbitofrontal/disinhibition model predicts that smokers will
      perform poorly on neurocognitive tasks considered sensitive to orbitofrontal
      dysfunction and will obtain significantly higher scores on measures of behavioral
      disinhibition and antisocial personality relative to nonsmokers. To test these
      predictions, we administered a battery of neuropsychological tests, clinical
      scales, and personality questionnaires to university student smokers and
      nonsmokers. Results did not support the self-medication model or the ADHD/self
      medication model; however, findings were consistent with the
      orbitofrontal/disinhibition model.

PMID- 14667425
TI  - Alcohol, tobacco, and other drug use among Asian American and Pacific Islander
      Adolescents in California and Hawaii.
AB  - As an aggregate group, the lowest rates of alcohol, tobacco, and other drug
      (ATOD) use are often reported for Asian Americans/Pacific Islanders (AAPIs),
      compared to other groups. However, the low rates are often based upon samples
      with small representations of AAPIs, or represented by only one or two AAPI
      groups. Consequently, reliable data on the rates of ATOD use among specific AAPI
      subgroups are severely lacking. Using data from school surveys collected from 9th
      grade students in California and 10th grade students in Hawaii, we compared the
      ATOD rates of Whites, Chinese, Filipino, Japanese, and Pacific Islander/Native
      Hawaiian adolescents. We found considerable variation in ATOD rates among
      subgroups of AAPIs, variation that was consistent across surveys. Chinese
      reported the lowest ATOD rates; Whites, Pacific Islanders, and Native Hawaiians
      reported among the highest. We found similar variation in need for alcohol and
      other drug treatment for these groups. Implications of these findings and
      recommendations for future research are discussed.

PMID- 14667426
TI  - Alcohol problem recognition as a function of own and others' perceived drinking.
AB  - A self-regulation model was applied for predicting alcohol problem recognition.
      With the rate of others' alcohol use serving as a standard, problem recognition
      was predicted to increase the more one perceived one's drinking rate to be above
      others' use. Within the context of a classroom-administered survey, 707
      nonabstaining undergraduates reported their drinking rates and estimated other
      students' drinking rates for annual drinking frequency, average weekly drinking
      quantity, and recent heavy drinking frequency. The independent roles of one's own
      and others' drinking rates, as well as the discrepancy between these two rates in
      predicting problem recognition, were examined. Findings were consistent with a
      self-regulation account. Across measures, only own drinking rate independently
      predicted problem recognition. Others' drinking rate interacted with own drinking
      rate in predicting problem recognition on the quantity measure. Specifically, the
      more heavy drinkers perceived their own quantity to be above others', the higher
      their problem recognition. Finally, gender effects were observed. Although men
      reported higher problem recognition than women, women reflected more on their
      drinking rates for problem recognition.

PMID- 14667427
TI  - A cognitive model of binge drinking: the influence of alcohol expectancies and
      drinking refusal self-efficacy.
AB  - While binge drinking-episodic or irregular consumption of excessive amounts of
      alcohol-is recognised as a serious problem affecting our youth, to date there has
      been a lack of psychological theory and thus theoretically driven research into
      this problem. The current paper develops a cognitive model using the key
      constructs of alcohol expectancies (AEs) and drinking refusal self-efficacy
      (DRSE) to explain the acquisition and maintenance of binge drinking. It is
      suggested that the four combinations of the AE and DRSE can explain the four
      drinking styles. These are normal/social drinkers, binge drinkers, regular heavy
      drinkers, and problem drinkers or alcoholics. Since AE and DRSE are cognitive
      constructs and therefore modifiable, the cognitive model can thus facilitate the
      design of intervention and prevention strategies for binge drinking.

PMID- 14667428
TI  - Discriminating reinforcement expectancies for studying from future time
      perspective in the prediction of drinking problems.
AB  - In recent work, Levy and Earleywine [Addict. Behav. (2003)] have proposed an
      expectancy framework of choice for the study of alcohol abuse. Within this
      framework, the link between alcohol expectancies and drinking problems is studied
      in the context of expectancies for alternative behaviors. Preliminary findings
      showed that studying expectancies predicted drinking problems among college
      students who hold high positive alcohol expectancies. Since the expected gain
      from studying is inherently long-term, further validation of these results
      requires to discriminate studying expectancies from the personality construct of
      future time perspective (FTP), which has been previously shown to predict
      substance use. In this study, studying expectancies produced larger group
      differences than FTP on all measures of drinking problems and habits. These
      differences remained significant after controlling for FTP. The results of the
      current study thus replicate previous findings and provide further support for an
      expectancy model of choice. Future research may explore whether enhancing
      studying expectancies can reduce drinking problems among college and high school
      students.

PMID- 14667429
TI  - Social and cognitive factors contributing to the intention to undergo a smoking
      cessation treatment.
AB  - Elaborating on a recently developed perspective, it is predicted that interest in
      the use of smoking cessation treatments (SCTs) is typical of 'dissonant smokers,'
      that is, smokers who dearly want to quit but feel unable to do so. Further, it is
      assumed that the interest in the use of SCTs is more prevalent among subjects who
      believe in the efficacy of these treatments. Finally, it is assumed that past
      behavior has an important influence on the interest in the use of SCTs. The
      theory was tested using analysis of linear-structural relations (LISREL) on a
      Dutch national probability sample of 763 adults, all smoking cigarettes and/or
      cigars. Results show that interest in the use of SCTs was positively influenced
      by being old, information seeking about smoking cessation in the past, nicotine
      dependency, having undergone a SCT in the past, experiencing social stimulation
      for abstinence, seeing many advantages and or many disadvantages with regards to
      abstinence, and having a positive attitude towards SCTs.

PMID- 14667430
TI  - Compulsive smoking: the development of a Rasch homogeneous scale of nicotine
      dependence.
AB  - The unidimensionality of nicotine dependence has not been established firmly yet.
      The aim of this study was to assess the dimensionality of nicotine dependence,
      preferably meeting the strict assumptions of the Rasch model. First, we examined
      the validity of the Fagerstrom Test for Nicotine Dependence (FTND) [Br. J.
      Addict. 86 (1991) 1119.] in 1525 smokers who participated in a national survey
      considering smoking behavior. Two factors were found, suggesting that the FTND
      does not measure a unidimensional construct. Factor analysis of 19 other
      dependence items in 512 smokers resulted in four factors of which three were
      interpretable: compulsive smoking, social problems due to smoking, and physical
      dependence. We focused on smoking compulsivity. This factor turned out to consist
      of a four-item Rasch homogeneous scale. Two items of the FTND with face validity
      of smoking compulsivity were found to fit into the scale. The results of Rasch
      analysis were in support of a continuum of compulsivity. Difficulty refraining
      from smoking in places where it is forbidden was found to indicate highest
      compulsivity. Several correlates with smoking compulsivity were found. We
      conclude that compulsive smoking is one important dimension of nicotine
      dependence, which may account for the considerable relapse of this disorder.

PMID- 14667431
TI  - Size, consistency, and stability of stage effects for smoking cessation.
AB  - In the transtheoretical model (TTM), the stage effect is one of the most
      important determinants of health behavior change. Randomly assigned to 1 of 11
      treatment conditions were 4653 smokers. A total of 66 stage effects were possible
      with 6 for each of the 11 treatment groups. The results suggest that brief stage
      matched interventions that help populations progress one stage could produce 75%
      more abstinence. Interventions that help populations progress two stages could
      produce 300% more abstinence. The results also support the importance of
      replicating the stage effects across treatment conditions and over time.

PMID- 14667432
TI  - An experimental test of an alcohol expectancy challenge in mixed gender groups of
      young heavy drinkers.
AB  - Several studies have shown that a multisession experiential expectancy challenge
      successfully reduces positive alcohol expectancies and alcohol use in heavy
      drinking young men, but this has not been shown for heavy drinking young women.
      Main aim of this study was to test the effect of a multisession expectancy
      challenge in mixed gender groups of young heavy drinkers. Twenty-five (11 males)
      heavy drinking students were randomly assigned to the expectancy challenge or
      control condition (the challenge was adapted to be more suitable for women).
      Positive expectancies decreased significantly in the experimental but not in the
      control group. In the experimental group, positive expectancies decreased
      significantly more in women than in men, and alcohol use showed a statistical
      trend in the same direction. These findings are the first to indicate that a
      multisession expectancy challenge may result in reduced positive expectancies and
      alcohol consumption in young heavy drinking women. An important next question is
      whether a single experiential session could be effective because recruitment for
      a multisession challenge proved difficult, which is problematic for further
      implementation.

PMID- 14667433
TI  - Only one in three people with alcohol abuse or dependence ever seek treatment.
AB  - The proportion of respondents who had a lifetime diagnosis of alcohol abuse or
      dependence who ever attended addiction treatment was determined using data from a
      Canadian population survey. Only one in three of these respondents had ever
      attended treatment for their alcohol concerns. Respondents' age and severity of
      alcohol problem (alcohol abuse versus dependence) were significantly associated
      with addiction treatment attendance.

PMID- 14667434
TI  - Computer-mediated intervention to prevent drug abuse and violence among high-risk
      youth.
AB  - This research evaluated a computer-mediated intervention for preventing drug
      abuse and violence. Research participants were economically disadvantaged youth,
      defined as early adolescents from households with family incomes below the
      Federal poverty line. Based on cognitive-behavioral skills approaches shown
      effective in past research, computer intervention was compared with
      conventionally delivered intervention in a pretest-posttest, control group
      design. Outcome findings revealed that youth assigned to the computer or
      conventional intervention arms achieved more positive pretest-to-posttest gain
      scores than youth in the control arm on several variables. These variables were:
      how youth regarded people who used drugs, strategies for avoiding trouble, and
      ways for controlling their tempers. One item, the ability to refuse drug offers,
      favored youth in the conventional intervention arm over those in the computer or
      control arms. Combined with prior work on computer-delivered interventions, data
      from this study lend added support to the viability of computer approaches for
      preventing drug abuse, violence, and other problem behavior among early
      adolescent youth.

PMID- 14667435
TI  - 5-hydroxytryptamine 1A receptor activation reduces cutaneous vasoconstriction and
      fever associated with the acute inflammatory response in rabbits.
AB  - 5-Hydroxytryptamine(1A) (5-HT1A) receptor activation reduces body temperature
      partially by dilating the thermoregulatory cutaneous vascular bed, thereby
      increasing heat transfer to the environment. Constriction of this vascular bed,
      with consequent reduction of heat transfer to the environment, contributes to
      fever associated with the acute inflammatory response. Thus activation of 5-HT1A
      receptors might inhibit thermoregulatory cutaneous vasoconstriction and reduce
      the fever associated with the acute inflammatory response. The present study
      tested this hypothesis in conscious unrestrained rabbits. The acute inflammatory
      reaction was induced with i.v. lipopolysaccharide (LPS, 0.5 microg/kg). Body
      temperature was measured with an i.p. telemetric probe, and ear pinna blood flow
      was measured with a chronically implanted Doppler ultrasonic probe. 5-HT1A
      receptors were activated with i.v. 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH
      DPAT). LPS increased body temperature by +1.7+/-0.2 degrees C during the first
      hour after administration. The ear pinna Doppler blood flow signal fell from 69+/
      11 to 5+/-1 cm/s within 15 min (n=7, P<0.01) and remained at a low level for
      approximately 1 h after LPS. When administered 45 min after LPS, 8-OH-DPAT (0.1
      mg/kg i.v.) reversed this fall, increasing the Doppler signal from 6+/-1 to 55+/
      7 cm/s (P<0.01, n=6), and reduced the rise in body temperature. Treatment with 8
      OH-DPAT (0.1 mg/kg i.v.) 5 min before and 30 min after LPS entirely prevented the
      LPS-induced fall in ear pinna blood flow, and reduced the rise in body
      temperature from 1.7+/-0.2 degrees C to 0.7+/-0.2 (n=7, P<0.01). Treatment with
      WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2
      pyridinyl)cyclohexanecarboxamide trihydrochloride) (0.1 mg/kg i.v.) prevented and
      reversed the effects of 8-OH-DPAT. Thus activation of 5-HT1A receptors reduces
      thermoregulatory cutaneous vasoconstriction and fever occurring as part of the
      acute inflammatory response. Our findings elucidate the neurotransmitter
      mechanisms underlying expression of an important component of the febrile
      response, and suggest that drugs with 5-HT1A agonist properties might be
      therapeutically useful when it is clinically important to reduce this response.

PMID- 14667436
TI  - Cortical-area specific block of genetically determined absence seizures by
      ethosuximide.
AB  - Absence epilepsy is characterised by a paroxysmal loss of consciousness, of
      abrupt onset and termination, and is associated with a bilateral synchronous
      spike and wave discharge (SWD) on the electroencephalogram. Absence seizures
      involve an interplay between thalamic and cortical structures, although most
      research has so far focussed on sensory thalamic nuclei and the reticular
      thalamic nucleus (RTN). Thus, microinfusion of ethosuximide (ETX), a first choice
      anti-absence drug, into either the ventrobasal thalamus or RTN of the genetic
      absence epilepsy rat from Strasbourg (GAERS), a validated rat model of absence
      epilepsy, does not produce immediate cessation of seizure activity, as is seen
      following systemic administration. As recent evidence indicates a seizure
      initiation site within the peri-oral region of the primary somatosensory cortex
      (S1po), we have now applied ETX into S1po as well as the somatosensory cortex
      forelimb region (S1FL) and the motor cortex (M1) of freely moving GAERS.
      Microinfusion of 10 or 20 nmol/side of ETX into S1po produced an immediate
      cessation of seizure activity. A less marked response was produced when even a
      higher dose (200 nmol/side) was infused into S1FL. No reduction of SWD was seen
      when ETX was infused into M1. Microinfusion of CGP 36742 (5 nmol/side), a GABA(B)
      antagonist, produced immediate cessation of seizure activity in both S1po and M1
      and a delayed effect in S1FL. These data suggest that the ability of ETX to
      abolish genetically determined absence seizures is cortical-area specific and
      support the involvement of S1po in the initiation of SWDs.

PMID- 14667437
TI  - Knockdown of spinal cord postsynaptic density protein-95 prevents the development
      of morphine tolerance in rats.
AB  - The activation of spinal cord N-methyl-D-aspartate (NMDA) receptors and
      subsequent intracellular cascades play a pivotal role in the development of
      opioid tolerance. Postsynaptic density protein-95 (PSD-95), a molecular
      scaffolding protein, assembles a specific set of signaling proteins around NMDA
      receptors at neuronal synapses. The current study investigated the possible
      involvement of PSD-95 in the development of opioid tolerance. Opioid tolerance
      was induced by intrathecal injection of morphine sulfate (20 microg/10 microl)
      twice a day for 4 consecutive days. Co-administration of morphine twice daily and
      PSD-95 antisense oligodeoxynucleotide (50 microg/10 microl) once daily for 4 days
      not only markedly reduced the PSD-95 expression and its binding to NMDA receptors
      in spinal cord but also significantly prevented the development of morphine
      tolerance. In contrast, co-administration of morphine twice daily and PSD-95
      missense oligodeoxynucleotide (50 microg/10 microl) once daily for 4 days did not
      produce these effects. The PSD-95 antisense oligodeoxynucleotide at the doses we
      used did not affect baseline response to noxious thermal stimulation or locomotor
      function. The present study indicates that the deficiency of spinal cord PSD-95
      attenuates the development of opioid tolerance. These results suggest that PSD-95
      might be involved in the central mechanisms of opioid tolerance and provide a
      possible new target for prevention of development of opioid tolerance.

PMID- 14667438
TI  - Carbachol in the pontine reticular formation of C57BL/6J mouse decreases
      acetylcholine release in prefrontal cortex.
AB  - The prefrontal cortex and brainstem modulate autonomic and arousal state control
      but the neurotransmitter mechanisms underlying communication between prefrontal
      cortex and brainstem remain poorly understood. This study examined the hypothesis
      that microdialysis delivery of carbachol to the pontine reticular formation (PRF)
      of anesthetized C57BL/6J (B6) mouse modulates acetylcholine (ACh) release in the
      frontal association cortex. Microdialysis delivery of carbachol (8.8 mM) to the
      PRF caused a significant (P<0.01) decrease (-28%) in ACh release in the frontal
      association cortex, a significant (P<0.01) decrease (-23%) in respiratory rate,
      and a significant (P<0.01) increase (223%) in time to righting after anesthesia.
      Additional in vitro studies used the [(35)S]guanylyl-5'-O-(gamma-thio)
      triphosphate ([(35)S]GTPgammaS) assay to test the hypothesis that muscarinic
      cholinergic receptors activate guanine nucleotide binding proteins (G proteins)
      in the frontal association cortex and basal forebrain. In vitro treatment with
      carbachol (1 mM) caused a significant (P<0.01) increase in [(35)S]GTPgammaS
      binding in the frontal association cortex (62%) and basal forebrain nuclei
      including medial septum (227%), vertical (210%) and horizontal (165%) limbs of
      the diagonal band of Broca, and substantia innominata (127%). G protein
      activation by carbachol was concentration-dependent and blocked by atropine,
      indicating that the carbachol-stimulated [(35)S]GTPgammaS binding was mediated by
      muscarinic cholinergic receptors. Together, the in vitro and in vivo data show
      for the first time in B6 mouse that cholinergic neurotransmission in the PRF can
      significantly alter ACh release in frontal association cortex, arousal from
      anesthesia, and respiratory rate.

PMID- 14667439
TI  - Normalization of glutamate decarboxylase gene expression in the entopeduncular
      nucleus of rats with a unilateral 6-hydroxydopamine lesion correlates with
      increased GABAergic input following intermittent but not continuous levodopa.
AB  - The expression of mRNA encoding for the 67 kilodalton isoform of glutamate
      decarboxylase (GAD67) was examined by in situ hybridization histochemistry in the
      entopeduncular nucleus (EP) of adult rats with a 6-hydroxydopamine unilaterally
      lesion of dopamine neurons. Our results provide original evidence that continuous
      or intermittent levodopa administration is equally effective at reversing the
      lesion-induced increase in GAD67 mRNA expression in the EP when compared with
      vehicle controls. To characterize the GABAergic interactions that may mediate
      levodopa-induced alterations in the EP, double-labeling in situ hybridization was
      conducted with a combination of GAD67 radioactive and preproenkephalin or
      preprotachykinin digoxigenin-labeled complementary RNA probes in the striatum.
      Levels of GAD67 mRNA labeling were significantly increased by intermittent, but
      not continuous levodopa. Analysis at the cellular level in a dorsal sector of the
      striatum revealed that GAD67 mRNA levels increased predominantly in
      preproenkephalin-unlabeled neuronal profiles, presumably striatal/EP neurons
      (+99.3%). Saturation analyses of (3)H-flunitrazepam binding to GABA(A) receptors
      in the EP showed that the increase in GAD67 mRNA in preproenkephalin-unlabeled
      neurons by intermittent levodopa paralleled a significant decrease in number of
      GABA(A) receptors (Bmax) in the EP ipsilateral to the lesion. Continuous levodopa
      failed to alter striatal GAD67 mRNA levels, or the number or affinity of GABA(A)
      receptors when compared with vehicle-treated controls. These results suggest the
      normalization of GAD gene expression in the EP by intermittent levodopa involves
      an increase in GABAergic inhibition by striatonigral/EP neurons of the direct
      pathway. Conversely, the effects of continuous levodopa on GAD mRNA levels in the
      EP do not appear to be mediated by GABA.

PMID- 14667440
TI  - Mouse strains that lack spinal dynorphin upregulation after peripheral nerve
      injury do not develop neuropathic pain.
AB  - Several experimental models of peripheral neuropathy show that a significant
      upregulation of spinal dynorphin A and its precursor peptide, prodynorphin, is a
      common consequence of nerve injury. A genetically modified mouse strain lacking
      prodynorphin does not exhibit sustained neuropathic pain after nerve injury,
      supporting a pronociceptive role of elevated levels of spinal dynorphin. A null
      mutation of the gamma isoform of protein kinase C (PKCgamma KO [knockout]), as
      well as an inbred mouse strain, 129S6, also does not manifest behavioral signs of
      neuropathic pain following peripheral nerve injury. The objective of this study
      was to extend our observations to these genetic models to test the hypothesis
      that elevated levels of spinal dynorphin are essential for the maintenance of
      abnormal pain. In PKCgamma wild-type mice and the outbred mouse strain ICR,
      ligation of the L5 and L6 spinal nerves (SNL) elicited both tactile
      hypersensitivity and thermal hyperalgesia. Both strains showed a significant
      elevation in dynorphin in the lumbar spinal dorsal horn following SNL. Spinal
      administration of an anti-dynorphin A antiserum blocked the thermal and tactile
      hypersensitivity in both strains of mice. However, the PKCgamma KO mice and the
      129S6 mice (which express PKCgamma) did not show abnormal pain after SNL; neither
      strain showed elevated levels of spinal dynorphin. The multiple phenotypic
      deficits in PKCgamma KO mice confound the interpretation of the proposed role of
      PKCgamma-expressing spinal neurons in neuropathic pain states. Additionally, the
      data show that the regulation of spinal dynorphin expression is a common critical
      feature of expression of neuropathic pain.

PMID- 14667441
TI  - Neuronal activity in the periaqueductal gray and bordering structures during
      vocal communication in the squirrel monkey.
AB  - In seven freely moving squirrel monkeys (Saimiri sciureus), the neuronal activity
      in the periaqueductal gray (PAG) and bordering structures was registered during
      vocal communication, using a telemetric single-unit recording technique. In 9.3%
      of the PAG neurons, a vocalization-correlated activity was found. Four reaction
      types could be distinguished: a) neurons, showing an activity burst immediately
      before vocalization onset; b) neurons, firing during vocalization, and starting
      shortly before vocalization onset; c) neurons, firing exclusively during
      vocalization; d) neurons, firing in the interval between perceived vocalizations
      (i.e. vocalizations produced by group mates) and self-produced vocal response.
      All PAG neurons showed a marked vocalization-type specificity. None of the
      neurons reflected simple acoustic parameters, such as fundamental frequency or
      amplitude, in its discharge rate. None of the neurons reacted to vocalizations of
      other animals not responded to by the experimental animal. All four reaction
      types found in the PAG were also found in the reticular formation bordering the
      PAG, though in lower density.

PMID- 14667442
TI  - Muscarinic autoreceptors related with calcium channels in the strong and weak
      inputs at polyinnervated developing rat neuromuscular junctions.
AB  - Using intracellular recording, we studied how several muscarinic antagonists
      affected the evoked endplate potentials in singly and dually innervated endplates
      of the levator auris longus muscle from 3 to 6-day-old rats. In dually innervated
      fibers, a second endplate potential (EPP) may appear after the first one when we
      increase the stimulation intensity. The lowest and highest EPP amplitudes are
      designated "small-EPP" and "large-EPP," respectively. In singly innervated
      endplates and large-EPP, we found an inhibition of acetylcholine release by M1
      receptor antagonists pirenzepine and MT-7 (more than 30%) and M2-receptor
      antagonists methoctramine and AF-DX 116 (more than 40%). The small-EPP was also
      inhibited by both M2-receptor antagonists methoctramine (approximately 70%) and
      AF-DX 116 (approximately 40%). However, the small-EPP was enhanced by M1-receptor
      antagonists pirenzepine (approximately 90%) and MT-7 (approximately 50%). The M4
      receptor selective antagonists tropicamide and MT-3 can also increase the small
      EPP amplitude (75% and 120%, respectively). We observed a graded change from a
      multichannel involvement (P/Q- N- and L-type voltage-dependent calcium channels)
      of all muscarinic responses (M1-, M2- and M4-mediated) in the small-EPP to the
      single channel (P/Q-type) involvement of the M1 and M2 responses in the singly
      innervated endplates. This indicates the existence of a progressive calcium
      channels shutoff in parallel with the specialization of the adult type P/Q
      channel. In conclusion, muscarinic autoreceptors can directly modulate large-EPP
      generating ending potentiation, and small-EPP generating ending depression
      through their association with the calcium channels during development.

PMID- 14667443
TI  - Differential expression of alpha 1 and beta subunits of voltage dependent Ca2+
      channel at the neuromuscular junction of normal and P/Q Ca2+ channel knockout
      mouse.
AB  - Voltage-dependent calcium channels (VDCC) have a key role in neuronal function
      transforming the voltage signals into intracellular calcium signals. They are
      composed of the pore-forming alpha(1) and the regulatory alpha(2)delta, gamma and
      beta subunits. Molecular and functional studies have revealed which alpha(1)
      subunit gene product is the molecular constituent of each class of native calcium
      channel (L, N, P/Q, R and T type). Electrophysiological and immunocytochemical
      studies have suggested that at adult mouse motor nerve terminal (MNT) only P/Q
      type channels, formed by alpha(1A) subunit, mediate evoked transmitter release.
      The generation of alpha(1A)-null mutant mice offers an opportunity to study the
      expression and localization of calcium channels at a synapse with complete loss
      of P/Q calcium channel. We have investigated the expression and localization of
      VDCCs alpha(1) and beta subunits at the wild type (WT) and knockout (KO) mouse
      neuromuscular junction (NMJ) using fluorescence immunocytochemistry. The
      alpha(1A) subunit was observed only at WT NMJ and was absent at denervated
      muscles and at KO NMJ. The subunits alpha(1B), alpha(1D) and alpha(1E) were also
      present at WT NMJ and they were over- expressed at KO NMJ suggesting a
      compensatory expression due to the lack of the alpha(1A). On the other hand, the
      beta(1b), beta(2a) and beta(4) were present at the same levels in both genotypes.
      The presence of other types of VDCC at WT NMJ indicate that they may play other
      roles in the signaling process which have not been elucidated and also shows that
      other types of VDCC are able to substitute the alpha(1A) subunit, P/Q channel
      under certain pathological conditions.

PMID- 14667444
TI  - Potential pathways for intercellular communication within the calbindin
      subnucleus of the hamster suprachiasmatic nucleus.
AB  - In mammals, the suprachiasmatic nucleus (SCN) is the master circadian pacemaker.
      Within the caudal hamster SCN, a cluster of neurons containing the calcium
      binding protein, calbindin-D28K (CB), has been implicated in circadian
      locomotion. However, calbindin-immunoreactive (CB+) neurons in the calbindin
      subnucleus (CBsn) do not display a circadian rhythm in spontaneous firing [Eur J
      Neurosci 16 (2002) 2469]. Previously, we proposed that intercellular
      communication might be essential in integrating outputs from rhythmic (CB-)
      neurons and nonrhythmic (CB+) neurons to produce a circadian output in the intact
      animal. The primary aim of this study is to provide a neuroanatomical framework
      to better understand intercellular communication within the CBsn. Using
      reconstructions of previously recorded neurons, we demonstrate that CB+ neurons
      have significantly more dendrites than CB- neurons. In addition, CBsn neurons
      have dorsally oriented dendritic arbors. Using double-label confocal microscopy,
      we show that GABA colocalizes with CB+ neurons and GABA(A) receptor subunits make
      intimate contacts with neurons in the CBsn. Transforming growth factor alpha
      (TGFalpha), a substance shown to inhibit locomotion [Science 294 (2001) 2511], is
      present within the CBsn. In addition, neurons in this region express the
      epidermal growth factor receptor, the only receptor for TGFalpha. Lastly, we show
      that CB+ neurons are coupled to CB+ and CB- neurons by gap junctions. The current
      study provides a structural framework for synaptic communication, electrical
      coupling, and signaling via a growth factor within the CBsn of the hamster SCN.
      Our results reveal connections that have the potential for integrating cellular
      communication within a subregion of the SCN that is critically involved in
      circadian locomotion.

PMID- 14667445
TI  - Abdominal surgery induces mu opioid receptor endocytosis in enteric neurons of
      the guinea-pig ileum.
AB  - Immunohistochemistry and confocal microscopy were used to investigate mu opioid
      receptor (muOR) internalization in enteric neurons of the guinea-pig ileum
      following abdominal surgery. The following surgical procedures were performed
      under halothane or isofluorane anesthesia: a) midline abdominal skin incision, b)
      laparotomy or c) laparotomy with intestinal manipulation. Gastrointestinal
      transit was evaluated by using a non-absorbable marker and measuring fecal pellet
      output. In neurons from normal and control (anesthesia alone) animals, muOR was
      predominantly at the cell surface. muOR endocytosis following skin incision was
      not significantly different from controls (21.2+/-3.5% vs. 13.7+/-2.1%, mean+/
      S.E.M.), whereas it was significantly increased by laparotomy (46.5+/-6.1%;
      P<0.01 vs. controls) or laparotomy plus intestinal manipulation (40.5+/-6.1%;
      P<0.01 vs. controls) 30 min following surgery compared with controls. muOR
      endocytosis remained elevated at 4 h (38.6+/-1.2%; P<0.01 vs. controls), whereas
      it was similar to controls at 6 and 12 h (17.5+/-5.8% and 11.2+/-3.0%). muOR
      endocytosis occurred in cholinergic and nitrergic neurons. Gastrointestinal
      transit was significantly delayed by laparotomy or laparotomy plus intestinal
      manipulation (12.8+/-1.2 and 13.8+/-0.6 h vs. 7.0+/-0.5 in controls; P<0.01), but
      was not significantly changed by skin incision (8.2+/-0.6 h). The findings of the
      present study support the concept that the noxious stimulation caused by
      abdominal surgery induces release of endogenous opioids thus resulting in muOR
      endocytosis in neurochemically distinct enteric neurons. muOR internalization can
      serve as indirect evidence of opioid release and as a means to visualize neuronal
      pathways activated by opioids.

PMID- 14667446
TI  - Functional coupling, desensitization and internalization of virally expressed mu
      opioid receptors in cultured dorsal root ganglion neurons from mu opioid receptor
      knockout mice.
AB  - Although mu opioid receptors desensitize in various cell lines in vitro, the
      relationship of this change in signaling efficacy to the development of tolerance
      in vivo remains uncertain. It is clear that a system is needed in which
      functional mu opioid receptor expression is obtained in appropriate neurons so
      that desensitization can be measured, manipulated, and mutated receptors
      expressed in this environment. We have developed a recombinant system in which
      expression of a flag-tagged mu opioid receptor is returned to dorsal root ganglia
      neurons from mu opioid receptor knockout mice in vitro. Flow cytometry analysis
      showed that adenoviral-mediated expression of the amino-terminal flag-tagged mu
      opioid receptor in neurons resulted in approximately 1.3x10(6) receptors/cell.
      Many mu opioid receptor cell lines express a similar density of receptors but
      this is approximately 7x greater than the number of endogenous receptors
      expressed by matched wild-type neurons. Inhibition of the high voltage-activated
      calcium currents in dorsal root ganglia neurons by the mu agonist, D-Ala(2), N
      MePhe(4), Gly(5)-ol-enkephalin (DAMGO), was not different between the endogenous
      and flag-tagged receptor at several concentrations of DAMGO used. Both receptors
      desensitized equally over the first 6 h of DAMGO pre-incubation, but after 24 h
      the response of the endogenous receptor to DAMGO had desensitized further than
      the flag- tagged receptor (71+/-3 vs 29+/-7% respectively; P<0.002), indicating
      less desensitization in neurons expressing a higher density of receptor. Using
      flow cytometry to quantify the percentage of receptors remaining on the neuronal
      cell surface, the flag-tagged receptor internalized by 17+/-1% after 20 min and
      55+/-2% after 24 h of DAMGO. These data indicate that this return of function
      model in neurons recapitulates many of the characteristics of endogenous mu
      opioid receptor function previously identified in non-neuronal cell lines.

PMID- 14667447
TI  - Roles of ryanodine and inositol triphosphate receptors in regulation of plateau
      potentials in turtle spinal motoneurons.
AB  - Generation of plateau potentials in spinal motoneurons depends on activation of
      voltage sensitive L-type Ca(2+) channels. These channels are facilitated by
      metabotropic receptors known to promote release of Ca(2+) from intracellular
      stores. The aim of this study is to determine if Ca(2+)-release receptors in the
      endoplasmic reticulum (ER) that are sensitive to ryanodine (RyRs) and to inositol
      triphosphate receptors (IP(3)Rs) contribute to the generation of plateau
      potentials. The effects of antagonists to RyRs, IP(3)Rs and phospholipase C (PLC)
      were tested on discharge patterns associated with plateau potentials in
      motoneurons in slices from the spinal cord of the turtle. Plateau-related
      discharge patterns, un-facilitated or facilitated by agonists for group I
      glutamate metabotropic receptors, muscarine-sensitive cholinergic receptors or L
      type Ca(2+) channels were inhibited by blockade of RyRs. In contrast, antagonists
      of IP(3)Rs or PLC preferentially inhibited plateau-related discharge patterns
      when facilitated by activation of metabotropic receptors but in only half of the
      cells when promoted in the absence of metabotropic facilitators. Our findings
      show that RyRs and IP(3)Rs regulate the generation of plateau potentials in
      motoneurons and suggest that RyRs may be directly involved with activation of the
      plateau potential.

PMID- 14667448
TI  - Immunolocalization of peroxisome proliferator-activated receptors and retinoid X
      receptors in the adult rat CNS.
AB  - Peroxisome proliferator-activated and retinoid X receptors (PPARs and RXRs) are
      transcription factors belonging to the steroid hormone receptor superfamily. Upon
      activation by their ligands, PPARs and RXRs bind to their target genes as
      heterodimers. Ligands of these receptors include lipophylic molecules, such as
      retinoids, fatty acids and eicosanoids, the importance of which in the metabolism
      and functioning of the nervous tissue is well documented. The immunohistochemical
      distribution of PPARs and RXRs in the CNS of the adult rat was studied by means
      of a sensitive biotinyl-tyramide method. All PPAR (alpha, beta/delta and gamma)
      and RXR (alpha, beta and gamma) isotypes were detected and found to exhibit
      specific patterns of localization in the different areas of the brain and spinal
      cord. The presence of the nuclear receptors was observed in both neuronal and
      glial cells. While PPAR beta/delta and RXR beta showed a widespread distribution,
      alpha and gamma isotypes exhibited a more restricted pattern of expression. The
      frontal cortex, basal ganglia, reticular formation, some cranial nerve nuclei,
      deep cerebellar nuclei, and cerebellar Golgi cells appeared rather rich in all
      studied receptors. Based on our data, we suggest that in the adult CNS, PPARs and
      RXRs, besides playing roles common to many other tissues, may have specific
      functions in regulating the expression of genes involved in neurotransmission,
      and therefore play roles in complex processes, such as aging, neurodegeneration,
      learning and memory.

PMID- 14667449
TI  - A neuroprotective role of extracellular signal-regulated kinase in N-acetyl-O
      methyldopamine-treated hippocampal neurons after exposure to in vitro and in vivo
      ischemia.
AB  - In response to cerebral ischemia, neurons activate survival/repair pathways in
      addition to death cascades. Activation of cyclic AMP-response-element-binding
      protein (CREB) is linked to neuroprotection in experimental animal models of
      stroke. However, a role of the mitogen-activated protein kinase/extracellular
      signal-regulated kinase kinase (MAPK/ERK or MEK), an upstream kinase for CREB,
      and its relation to CREB phosphorylation in neuroprotection in cerebral ischemia
      has not been delineated. Previously, we reported that N-acetyl-O-methyldopamine
      (NAMDA) significantly protected CA1 neurons after transient forebrain ischemia [J
      Neurosci 19 (1999b) 87.8]. The current study is to investigate whether NAMDA
      induced neuroprotection occurs via the activation of ERK and its downstream
      effector, CREB. NAMDA induced ERK1/2 and CREB phosphorylation with increased
      survival of HC2S2 hippocampal neurons subjected to oxygen-glucose deprivation.
      These effects were reversed by U0126, a MEK kinase inhibitor. Similarly, animals
      treated with NAMDA following ischemia showed increased ERK and CREB
      phosphorylation in the CA1 subregion of the hippocampus during early reperfusion
      period with increased number of surviving neurons examined 7 days following
      ischemia. The NAMDA-induced neuroprotection was abolished by U0126 administered
      shortly after reperfusion. The results showed that the ERK-CREB signaling pathway
      might be involved in NAMDA-induced neuroprotection following transient global
      ischemia and imply that the activation of the pathway in neurons may be an
      effective therapeutic strategy to treat stroke or other neurological syndromes.

PMID- 14667450
TI  - Transgenic mice expressing F3/contactin from the transient axonal glycoprotein
      promoter undergo developmentally regulated deficits of the cerebellar function.
AB  - We have shown that transgenic transient axonal glycoprotein (TAG)/F3 mice, in
      which the mouse axonal glycoprotein F3/contactin was misexpressed from a
      regulatory region of the gene encoding the transient axonal glycoprotein TAG-1,
      exhibit a transient disruption of cerebellar granule and Purkinje cell
      development [Development 130 (2003) 29]. In the present study we explore the
      neurobehavioural consequences of this mutation. We report on assays of
      reproductive parameters (gestation length, litter size and offspring viability)
      and on somatic and neurobehavioural end-points (sensorimotor development, homing
      performance, motor activity, motor coordination and motor learning). Compared
      with wild-type littermates, TAG/F3 mice display delayed sensorimotor development,
      reduced exploratory activity and impaired motor activity, motor coordination and
      motor learning. The latter parameters, in particular, were affected also in adult
      mice, despite the apparent recovery of cerebellar morphology, suggesting that
      subtle changes of neuronal circuitry persist in these animals after development
      is complete. These behavioural deficits indicate that the finely coordinated
      expression of immunoglobulin-like cell adhesion molecules such as TAG-1 and
      F3/contactin is of key relevance to the functional, as well as morphological
      maturation of the cerebellum.

PMID- 14667451
TI  - Alpha-2 adrenergic receptor development in rat CNS: an autoradiographic study.
AB  - During development norepinephrine plays a role in determining the morphologic
      organization of the CNS and the density and future responsiveness of adrenergic
      receptors. alpha-2 Adrenergic receptors, one of three adrenergic receptor types,
      regulate important adult CNS functions and may have a distinct role during
      development. We examined alpha-2 receptor distribution and density in the rat
      brain at postnatal days 1, 5, 10, 15, 21, 28 and in adults using the antagonist
      [(3)H]RX821002 for autoradiography. Binding kinetics and pharmacology for alpha-2
      adrenergic receptors were the same in adults and neonates. There was an overall
      increase in alpha-2 receptor levels during postnatal development with great
      variability in pattern and timing of receptor density changes among brain
      regions. Three major patterns were apparent. First, in many regions receptor
      density increased during postnatal development, generally reaching adult levels
      around postnatal day 15. Within this group there was variability in timing
      between regions and there were several regions with receptor densities higher
      than adult levels during the postnatal period. Second, there were regions with
      very high levels of receptors at birth and little or no change in density during
      the postnatal period. Third, some regions demonstrated decreasing or transient
      expression of alpha-2 adrenergic receptors in the course of postnatal
      development, including white matter regions, cerebellum and many brainstem
      nuclei, suggesting specific roles for alpha-2 receptors during development. This
      study investigates the development of alpha-2 adrenergic receptors in the rat
      CNS. It demonstrates there is region-specific regulation of alpha-2 receptor
      development and identifies brain regions where these receptors may play a
      specific and critical role in the regulation normal development.

PMID- 14667452
TI  - Nitric oxide-mediated activation of extracellular signal-regulated kinase (ERK)
      and c-jun N-terminal kinase (JNK) during hypoxia in cerebral cortical nuclei of
      newborn piglets.
AB  - Previous studies have shown that mitogen-activated protein kinases, such as
      extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK),
      mediate signal transduction from cell surface receptors to the nucleus and
      phosphorylate anti-apoptotic proteins thereby regulating programmed cell death.
      The present study tests the hypotheses that hypoxia activates ERK and JNK in
      neuronal nuclei of newborn piglets and the hypoxia-induced activation of ERK and
      JNK is mediated by nitric oxide (NO). Activated ERK and JNK were assessed by
      determining phosphorylated ERK and JNK using immunoblotting in six normoxic (Nx)
      and 10 hypoxic (Hx) and five N-nitro-L-arginine (a NOS inhibitor, 40 mg/kg,) 
      pretreated hypoxic (N-nitro-L-arginine [NNLA]-Hx) 3-5 day old piglets. Hypoxia
      was induced by decreasing inspired oxygen from 21% to 7% for 60 min. Cerebral
      tissue hypoxia was documented biochemically by determining the tissue levels of
      ATP and phosphocreatine (PCr). Cortical neuronal nuclei were isolated and the
      nuclear protein was analyzed for activated ERK and JNK using anti-phosphorylated
      ERK and JNK antibodies. Protein bands were detected using enhanced
      chemiluminescence method and analyzed by imaging densitometry. Protein density
      was expressed as absorbance ODxmm(2). ATP levels were 4.57+/-0.45 micromoles/g
      brain in the Nx group, 1.29+/-0.23 micromoles/g brain in the Hx group (P<0.05 vs
      Nx) and 1.50+/-0.14 micromoles/g brain in the NNLA-Hx group (P<0.05 vs Nx). PCr
      levels were 3.77+/-0.36 micromoles/g brain in the Nx group, 0.77+/-0.13
      micromoles/g brain in the hypoxic group (P<0.05) and 1.02+/-0.24 in the NNLA-Hx
      group (P<0.05 vs Nx). Density of phosphorylated ERK protein was 170.5+/-53.7
      ODxmm(2) in the Nx group as compared with 419.6+/-63.9 ODxmm(2) in the hypoxic
      group (P<0.001 vs Nx) and 270.0+/-28.7 in the NNLA-Hx group (P<0.002 vs Hx).
      Density of phosphorylated JNK protein was 172.8+/-42.8 ODxmm(2) in the normoxic
      group as compared with 364.6+/-60.1 ODxmm(2) in the Hx group (P<0.002) and
      254.8+/-24.8 in the NNLA-Hx group (P<0.002 vs Hx). The data demonstrate increased
      phosphorylation of ERK and JNK during hypoxia indicating that hypoxia results in
      activation of ERK and JNK in neuronal nuclei of newborn piglets. The
      administration of NNLA, a NOS inhibitor, prevented the hypoxia-induced
      phosphorylation of ERK and JNK indicating that the hypoxia-induced activation of
      ERK and JNK in the cerebral cortical nuclei of newborn piglets is NO-mediated

PMID- 14667453
TI  - Overwhelmingly asynchronous firing of rat subthalamic nucleus neurones in brain
      slices provides little evidence for intrinsic interconnectivity.
AB  - In Parkinson's disease the neurones of the subthalamic nucleus show increased
      synchrony and oscillatory burst discharge, thought to reflect a breakdown of
      parallel processing in basal ganglia circuitry. To understand better the
      mechanisms underlying this transition, we sought to mimic this change in firing
      pattern within sagittal slices of rat midbrain. The firing patterns of up to four
      simultaneously extracellularly recorded subthalamic nucleus (STN) neurones were
      analysed using burst and oscillation detection programs, and correlated activity
      between pairs of neurones assessed. In control conditions all but 11 of 488 (2%)
      neurones fired in a predominantly tonic pattern (with mean oscillation frequency
      >3 Hz), with no significantly cross-correlated activity in any of 393 pairs of
      neurones. The glutamate antagonists DL-2-amino-phosphonopentanoic acid (APV), 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6-methyl-2-(phenylethynyl)pyridine
      (MPEP) did not change the firing rate or pattern of these cells, providing no
      evidence for a role of glutamatergic collaterals within the STN under these
      conditions. The GABA(A) receptor antagonist bicuculline and GABA(B) receptor
      antagonist (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2
      hydroxypropyl]phenylmethyl phosphinic acid (CGP 55845) were also without effect
      on firing rate or pattern in these cells, suggesting that there was no active
      input from other GABAergic basal ganglia nuclei in this slice. The dopamine
      receptor antagonist haloperidol caused no significant change to firing rate or
      pattern of firing in these cells, suggesting that there was no active
      dopaminergic input in this slice. Excitations of STN neurones by muscarine, (+)-1
      aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD), N-methyl-D-aspartic acid
      (NMDA) or dopamine were all unaccompanied by a change in firing pattern or any
      significant correlated activity between STN neurone pairs. Burst firing could be
      induced in STN neurones with either the potassium channel blocker
      tetraethylammonium (TEA; 10 mM; in 100/138 [72%] of cells) or with a combination
      of NMDA and the calcium-activated potassium channel blocker apamin (in 101/216
      [47%] of cells). Burst firing in TEA was unchanged by CNOX and APV, MPEP,
      CGP55845, haloperidol, dopamine, and ACPD, although muscarine produced a
      significant increase in oscillation frequency. Burst firing in NMDA and apamin
      was unchanged by CNQX and APV, dopamine, muscarine and ACPD, although bicuculline
      caused a significant increase in oscillation frequency. Such burst firing was not
      accompanied by synchrony in any condition, either alone, or during application of
      excitatory agents or glutamate or GABA antagonists. As the bursting seen here was
      unaccompanied by the synchronous activity that has often been observed
      (pathologically) in vivo, it probably reflects solely intrinsic STN neuronal
      properties, rather than network activity. No functional role was found for
      glutamatergic collaterals within the STN, either when cells are firing tonically
      or burst firing. The circuitry needed to produce synchrony in the STN is most
      likely not intrinsic to the STN itself, but requires connections with other basal
      ganglia nuclei, and/or the cortex, which are not present in this preparation.

PMID- 14667454
TI  - Role of 5-HT1B receptors in entrainment disorder of Otsuka Long Evans Tokushima
      fatty (OLETF) rats.
AB  - The role of 5-HT1A and 5-HT1B receptors in entrainment function was studied in
      Otsuka Long Evans Tokushima fatty (OLETF) rats and control Long Evans Tokushima
      Otsuka (LETO) rats. Light-induced (100 lux, 30 min) Fos expression in the
      suprachiasmatic nucleus was studied. Light-induced Fos expression was
      significantly decreased in OLETF rats compared to that in LETO rats. The decrease
      of light-induced Fos expression in OLETF rats was significantly reversed by
      pretreatment with the 5-HT1B receptor antagonist, isamoltan (3 mg/kg, i.p.).
      Simultaneous administration of CGS12066B (5 mg/kg, i.p.), a 5-HT1B agonist,
      blocked the reversal effect of isamoltan on Fos expression. Fos expression was
      not changed in LETO rats by pretreatment with isamoltan (3 mg/kg, i.p.). The Fos
      expression in LETO and OLETF rats was significantly decreased by pretreatment
      with the 5-HT1A antagonist, WAY-100,635. Phase shifts in locomotor activity
      paralleled the Fos expression. Light-induced phase shifts of locomotor activity
      in OLETF rats were significantly smaller than those in LETO rats. The phase
      shifts were significantly increased by isamoltan (3 mg/kg, i.p.) in OLETF rats.
      These results suggest that 5-HT1B receptors are involved in the reduced
      entrainment function of OLETF rats.

PMID- 14667455
TI  - Delayed onset of Huntington's disease in mice in an enriched environment
      correlates with delayed loss of cannabinoid CB1 receptors.
AB  - Huntington's disease (HD) is a late onset progressive genetic disorder
      characterised by motor dysfunction, personality changes, dementia and premature
      death. The disease is caused by an unstable expanded trinucleotide (CAG) repeat
      encoding a polyglutamine stretch in the IT15 gene for huntingtin, a protein of
      unknown function. Transgenic mice expressing exon one of the human HD gene with
      an expanded polyglutamine region develop many features of human HD. Exposure of
      these mice to an "enriched" environment delays the onset of motor disorders and
      slows disease progression [Nature 404 (2000) 721]. We have compared the levels of
      receptor binding of a range of basal ganglia neurotransmitter receptors believed
      to be important in HD, in normal mice and R6/1 transgenic HD mice housed in
      either enriched or standard laboratory environments. HD mice housed in a normal
      environment show a loss of cannabinoid CB1 and dopamine D1 and D2 receptors in
      the striatum and the corresponding output nuclei of the basal ganglia. HD mice
      exposed to an enriched environment show equivalent loss of D1 and D2 receptors as
      their "non-enriched" counterparts; in contrast, the "enriched" mice show
      significantly less depletion of CB1 receptors. In the brains of humans diagnosed
      with HD cannabinoid CB1 receptors are selectively lost from the basal ganglia
      output nuclei prior to the development of other identifiable neuropathology
      [Neuroscience 97 (2000) 505]. Our results therefore show that an enhanced
      environment slows the rate of loss of one of the first identifiable neurochemical
      deficits of HD. This suggests that delaying the loss of CB1 receptors, either by
      environmental stimulation or pharmacologically, may be beneficial in delaying
      disease progression in HD patients.

PMID- 14667456
TI  - Contribution of peripheral N-methyl-D-aspartate receptors to c-fos expression in
      the trigeminal spinal nucleus following acute masseteric inflammation.
AB  - In this study, we examined the contribution of N-methyl-D-aspartate (NMDA)
      receptors on c-fos expression in the trigeminal brainstem nuclei following acute
      muscle inflammation. Mustard oil (MO; 20%, 30 microL) injected into the masseter
      muscle induced extensive peripheral edema and Fos-like immunoreactivity (Fos-LI)
      in several trigeminal brainstem areas including the subnucleus caudalis of the
      trigeminal spinal nucleus (Vc), the ventral and dorsal regions of the
      Vc/subnucleus interpolaris transition zone, and the paratrigeminal nucleus. In
      order to assess the effect of antagonizing NMDA receptors on MO-induced Fos-LI,
      rats were pre-treated with two different doses of i.v. MK-801 (0.3 mg/kg, 3
      mg/kg), a non-competitive NMDA receptor antagonist, 30 min prior to MO injection.
      Additional groups of rats received MK-801 (0.3 mg/kg) directly in the masseter
      muscle or in the biceps muscle 5 min prior to MO injection. A higher dose of i.v.
      MK-801 (3 mg/kg) and MK-801 given locally into the masseter muscle (0.3 mg/kg)
      produced a significant reduction in total number of MO-induced Fos-LI. Further
      analyses revealed that pre-treatment with MK-801 (3 mg/kg i.v.) significantly
      reduced the Fos-LI all throughout the Vc. Only at the caudal Vc, there was a dose
      dependent reduction of MO induced Fos-LI. Pre-treatment with masseteric MK-801
      also significantly reduced the Fos-LI in the caudal Vc, with the effect greater
      than that produced by the same dose of MK-801 given intravenously. These results
      suggest that peripheral NMDA receptors contribute to nociceptive processing from
      craniofacial muscles.

PMID- 14667457
TI  - Group I metabotropic glutamate receptors in spiral ganglion neurons contribute to
      excitatory neurotransmissions in the cochlea.
AB  - Evidence has accumulated over the years supporting glutamate as the primary
      neurotransmitter used by hair cells in afferent cochlear neurotransmission.
      Besides acting on ionotropic glutamate receptors, glutamate also activates second
      messenger systems via G-protein-coupled metabotropic glutamate receptors (mGluRs)
      to modulate neuronal excitability. However, it is unclear whether mGluRs
      participate in cochlear neurotransmission. We present evidence directly
      supporting a functional role for group I metabotropic glutamate receptors
      (mGluRIs) in spiral ganglion (SG) neurons. The presence of mGluRI and downstream
      G-protein subunits was demonstrated by molecular biology and immunolabeling
      methods. Direct activation of mGluRIs in cultured SG neurons resulted in
      transient increases of intracellular Ca(++) concentration and transient inward
      currents that gave rise to firings of multiple action potentials. These responses
      showed mGluRI pharmacological specificity and quickly desensitized. We next
      examined changes in cochlear function after noise exposure as a result of
      pharmacologically manipulating cochlear glutamate neurotransmission. These in
      vivo tests showed that blocking non-N-methyl-D-aspartic acid glutamate receptors
      was sufficient to eliminate compound action potentials of the auditory nerve, and
      pharmacologically inhibiting mGluRIs in the cochlea did not significantly affect
      the hearing threshold. In contrast, blocking mGluRIs lowered the amplitude of
      compound action potentials at louder sound levels and reduced the noise-induced
      temporary threshold shift. Our results suggest that although mGluRIs did not
      initiate fast excitatory cochlear neurotransmission, their activation contributed
      to the growth of excitatory responses of the cochlea. As a result, the cochlea
      was more resistant to noise-induced temporary hearing losses without the
      activation of mGluRIs in SG neurons.

PMID- 14667458
TI  - Simple and complex visual motion response properties in the anterior medial bank
      of the lateral suprasylvian cortex.
AB  - The cortical regions surrounding the suprasylvian sulcus have previously been
      associated with motion processing. Of the six areas originally described by
      Palmer et al. [J Comp Neurol 177 (1978) 237], the posteromedial lateral
      suprasylvian (PMLS) cortex has attracted the greatest attention. Very little
      physiological information is available concerning other suprasylvian visual
      areas, and in particular, the anteromedial lateral suprasylvian cortex (AMLS).
      Based on its cortical and sub-cortical connectivity patterns, the AMLS cortex is
      a likely candidate for higher-order motion processing in cat visual cortex. We
      have investigated this possibility by studying the receptive field sensitivity of
      AMLS neurons to complex motion stimuli. Neurons in AMLS cortex exhibited large
      (mean of 354 degrees (2)) and complex-like receptive fields, and most of them
      (74%) were classified as direction selective on the basis of their responses to
      sinusoidal drifting gratings. Most importantly, direction selectivity was present
      for complex motion stimuli. A subset of the neurons sampled (eight of 38 cells;
      21%) exhibited pattern-motion selectivity in response to moving plaid patterns.
      The capacity of AMLS neurons to signal higher-order stimuli was further supported
      by their selectivity to moving complex random-dot kinematograms. Finally, 45% of
      20 neurons were direction selective to a radial optic flow stimulus. Overall,
      these results suggest that AMLS cortex is involved in higher-order analyses of
      visual motion. It is possible that the AMLS cortex represents a region between
      PMLS and the anterior ectosylvian visual area in a functional hierarchy of areas
      involved in motion integration.

PMID- 14667459
TI  - Localization of vesicular glutamate transporters and neuronal nitric oxide
      synthase in rat nucleus tractus solitarii.
AB  - Previously we reported that glutamate and neuronal nitric oxide synthase (nNOS)
      colocalize in neurons of the nucleus tractus solitarii (NTS). That finding
      provided anatomical support for the suggestion that nitric oxide and glutamate
      interact in cardiovascular regulation by the NTS. Here we test the hypothesis
      that nNOS colocalizes with vesicular glutamate transporters (VGluT1 and VGluT2)
      in the NTS. Immunoreactivity (IR) for VGluT better identifies glutamatergic
      terminals than does glutamate-IR, which may label metabolic as well as
      transmitter stores of the amino acid. We used fluorescent immunohistochemistry
      combined with confocal laser scanning microscopy to study IR for VGluT1, VGluT2
      and nNOS in rat NTS. A high density of VGluT1-IR positive fibers was present in
      the gracilis and cuneatus nuclei while in the NTS we found a moderate density in
      the lateral and interstitial subnuclei and a low density in the dorsolateral,
      ventral and intermediate subnuclei. The medial, central, commissural and
      gelatinosus subnuclei contained few VGluT1-IR containing fibers. Thus, VGluT1
      containing fibers are not prominent in portions of the NTS where cardiovascular
      afferent fibers terminate. In contrast, we found a high density of VGluT2-IR
      containing fibers in the gelatinosus subnucleus and subpostremal area and a
      moderate density in cardiovascular regions such as the dorsolateral and medial
      subnuclei as well as in the central and lateral subnuclei. We found a low density
      in the ventral, intermediate, interstitial and commissural subnuclei. VGluT1-IR
      and VGluT2-IR rarely colocalized in fibers within the NTS. VGluT1-IR did not
      colocalize with nNOS, but VGluT2-IR and nNOS-IR colocalized in fibers in all NTS
      subnuclei. When compared with the other NTS subnuclei, the dorsolateral,
      gelatinosus and subpostremal subnuclei had higher frequencies of colocalization
      of VGluT2-IR and nNOS-IR. VGluT2-IR positive fibers were also apposed to nNOS-IR
      positive fibers throughout the NTS. These data support our hypothesis and confirm
      that glutamatergic fibers in the NTS contain nNOS.

PMID- 14667460
TI  - Chemically defined feedback connections from infragranular layers of sensory
      association cortices in the rat.
AB  - The primary visual (V1), auditory (AI), and somatosensory (SI) cortices are
      reciprocally connected with their respective sensory association cortices. In the
      rat, we have previously demonstrated that some of the connections arising from
      the secondary somatosensory (SII) and parietal insular (PA) cortices and
      terminating in the SI, are characterized by the expression of latexin, a
      candidate protein of carboxypeptidase A inhibitor. Here, by using retrograde
      tracing and latexin-immunohistochemistry, we show that latexin-expressing neurons
      in other association cortices of different sensory modalities also contribute to
      the feedback projections to the corresponding primary sensory cortices. These are
      the lateral part of the secondary visual cortex (V2L), temporal association
      cortex, and the dorsal and ventral (AIIv) parts of the secondary auditory belt
      cortex. Within sublayer VIa of the V2L, AIIv and SII, the majority of the V1-, AI
      and SI-projecting neurons respectively, are latexin-immunopositive. In contrast
      to feedback connections, far fewer latexin-expressing neurons participate in
      callosal or intrahemispheric feedforward connections. The latexin-expressing
      neurons constitute a virtually completely different population from
      corticothalamic neurons within the infragranular layers. Given that latexin might
      participate in the modulation of neuronal activity by controlling the protease
      activity, latexin-expressing feedback pathways would play a unique role in the
      modulation of sensory perception.

PMID- 14667461
TI  - Halothane augments event-related gamma oscillations in rat visual cortex.
AB  - Cortical gamma oscillations have been associated with neural processes supporting
      cognition and the state of consciousness but the effect of general anesthesia on
      gamma oscillations is controversial. Here we studied the concentration-dependent
      effect of halothane on gamma (20-60 Hz) power of event-related potentials (ERP)
      in rat primary visual cortex. ERP to light flashes repeated at 5-s intervals was
      recorded with chronically implanted, bipolar, intracortical electrodes at
      selected steady-state halothane concentrations between 0 and 2%. gamma-Band power
      was calculated for 0-1000, 0-300 and 300-1000 ms poststimulus periods and
      corresponding prestimulus (PS) periods. Multitaper power spectral analysis was
      used to estimate gamma power from both single-trial and average ERP in order to
      differentiate between phase-locked (evoked) and non-phase-locked (induced) gamma
      activities. Significant PS gamma power was present at all halothane
      concentrations. Flash elicited an increase in gamma power that lasted up to 1 s
      poststimulus at all halothane concentrations. Halothane at intermediate
      concentrations (0.5-1.2%) augmented both PS and ERP gamma power two to four times
      relative to the waking baseline. gamma Power was not different between waking and
      deeply anesthetized (2%) levels. gamma Power reached maximum, as predicted by a
      Gaussian fit of power-concentration data, at halothane concentration (0.86%)
      similar to the concentration (0.73%) that abolished the righting reflex, a
      behavioral index of loss of consciousness. Evoked, i.e. stimulus-locked, gamma
      power was present during the first 300 ms poststimulus but not later, and was
      approximately 50% of single-trial ERP gamma power. Single-trial gamma power was
      present also at 300-1000 ms poststimulus, reflecting ERP not phase-locked to the
      stimulus. In summary, these observations suggest that (1) gamma activity is
      present in states ranging from waking to deep halothane anesthesia, (2) halothane
      does not prevent the transfer of visual input to striate cortex even at surgical
      plane of anesthesia, and (3) anesthetic-induced loss of consciousness, as
      reflected by the loss of righting reflex, is not correlated with a reduction in
      gamma power. Variance with other studies may be due to an underestimation of
      gamma power by ERP signal averaging as compared with single-trial analysis.

PMID- 14667462
TI  - Comparative fos immunoreactivity in the brain after forebrain, brainstem, or
      combined seizures induced by electroshock, pentylenetetrazol, focally induced and
      audiogenic seizures in rats.
AB  - To help discern sites of focal activation during seizures of different phenotype,
      the numbers of Fos immunoreactive (FI) neurons in specific brain regions were
      analyzed following "brainstem-evoked," "forebrain-evoked" and forebrain/brainstem
      combination seizures induced by a variety of methods. First, pentylenetetrazol
      (PTZ, 50 mg/kg) induced forebrain-type seizures in some rats, or forebrain
      seizures that progressed to tonic/clonic brainstem-type seizures in other rats.
      Second, minimal electroshock induced forebrain seizures whereas maximal
      electroshock (MES) induced tonic brainstem-type seizures in rats. Third,
      forebrain seizures were induced in genetically epilepsy-prone rats (GEPRs) by
      microinfusion of bicuculline into the area tempestas (AT), while brainstem
      seizures in GEPRs were induced by audiogenic stimulation. A final set was
      included in which AT bicuculline-induced forebrain seizures in GEPRs were
      transiently interrupted by audiogenic seizures (AGS) in the same animals. These
      animals exhibited a sequence combination of forebrain clonic seizure, brainstem
      tonic seizure and back to forebrain clonic seizures. Irrespective of the methods
      of induction, clonic forebrain- and tonic/clonic brainstem-type seizures were
      associated with considerable Fos immunoreactivity in several forebrain
      structures. Tonic/clonic brainstem seizures, irrespective of the methods of
      induction, were also associated with FI in consistent brainstem regions. Thus,
      based on Fos numerical densities (FND, numbers of Fos-stained profiles),
      forebrain structures appear to be highly activated during both forebrain and
      brainstem seizures; however, facial and forelimb clonus characteristic of
      forebrain seizures are not observable during a brainstem seizure. This
      observation suggests that forebrain-seizure behaviors may be behaviorally masked
      during the more severe tonic brainstem seizures induced either by MES, PTZ or AGS
      in GEPRs. This suggestion was corroborated using the sequential seizure paradigm.
      Similar to findings using MES and PTZ, forebrain regions activated by AT
      bicuculline were similar to those activated by AGS in the GEPR. However, in the
      combination seizure group, those areas that showed increased FND in the forebrain
      showed even greater FND in the combination trial. Likewise, those areas of the
      brainstem showing FI in the AGS model, showed an even greater effect in the
      combination paradigm. Finally, the medial amygdala, ventral hypothalamus and
      cortices of the inferior colliculi showed markedly increased FND that appeared
      dependent upon activation of both forebrain and brainstem seizure activity in the
      same animal. These findings suggest these latter areas may be transitional areas
      between forebrain and brainstem seizure interactions. Collectively, these data
      illustrate a generally consistent pattern of forebrain Fos staining associated
      with forebrain-type seizures and a consistent pattern of brainstem Fos staining
      associated with brainstem-type seizures. Additionally, these data are consistent
      with a notion that separate seizure circuitries in the forebrain and brainstem
      mutually interact to facilitate one another, possibly through involvement of
      specific "transition mediating" nuclei.

PMID- 14667464
TI  - Genotoxicity testing of the furylethylene derivative 1-(5-bromofur-2-yl)-2-bromo
      2-nitroethene in cultured human lymphocytes.
AB  - The genotoxic potential of the compound 1-(5-bromofur-2-yl)-2-bromo-2-nitroethene
      (G-1) was evaluated in peripheral blood lymphocytes cultured in vitro, at
      concentrations ranging from 1 to 20 microg/ml. Micronuclei (MN) and sister
      chromatid exchanges (SCE) were scored as biomarkers of genotoxic effects. To
      detect the role of metabolic enzymes on the genotoxicity of this furylethylenic
      derivative, cultures for MN and SCE demonstrations were treated for 3 h with and
      without the S9 microsomal fraction as well as for 48 h without S9. Under the
      conditions of the study, the test agent did not induce significant increases in
      the frequency of micronucleated cells, irrespective of the presence/absence of
      the metabolic fraction. Nevertheless, a slight/moderate increase in the SCE
      frequency was observed in those cultures treated without the S9 mix. In addition,
      cytotoxic/cytostatic effects of the G-1 compound were observed mainly in cultures
      without S9 fraction, as indicated by the reduction of cell proliferation measured
      by the cytokinesis block proliferation index (CBPI) and the proliferative rate
      index (PRI).

PMID- 14667463
TI  - The FEMA GRAS assessment of cinnamyl derivatives used as flavor ingredients.
AB  - This publication is the seventh in a series of safety evaluations performed by
      the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In
      1993, the Panel initiated a comprehensive program to re-evaluate the safety of
      more than 1700 GRAS flavoring substances under conditions of intended use.
      Elements that are fundamental to the safety evaluation of flavor ingredients
      include exposure, structural analogy, metabolism, pharmacokinetics and
      toxicology. Flavor ingredients are evaluated individually and in the context of
      the available scientific information on the group of structurally related
      substances. Scientific data relevant to the safety evaluation of the use of
      cinnamyl derivatives as flavoring ingredients is evaluated.

PMID- 14667466
TI  - Inhibition of N-acetyltransferase activity and gene expression in human colon
      cancer cell lines by diallyl sulfide.
AB  - Diallyl sulfide (DAS) is one of the major components of garlic (Allium sativum)
      and is widely used in the world for food. In this study, DAS was selected for
      testing the inhibition of arylamine N-acetyltransferase (NAT) activity (N
      acetylation of 2-aminofluorene) and gene expression (mRNA NAT) in human colon
      cancer cell lines (colo 205, colo 320 DM and colo 320 HSR). The NAT activity was
      examined by high performance liquid chromatography and indicated that a 24 h DAS
      treatment decreases N-acetylation of 2-aminofluorene in three colon (colo 205,
      320 DM and colo 320 HSR) cancer cell lines. The NAT enzymes (protein) were
      analyzed by western blotting and flow cytometry and it indicated that DAS
      decreased the levels of NAT in three colon (colo 205, 320 DM and colo 320 HSR)
      cancer cell lines. The gene expression of NAT (mRNAT NAT) was determined by
      polymerase chain reaction (PCR), it was shown that DAS affect mRNA NAT expression
      in examined human colon cancer cell lines. This report is the first to
      demonstrate that DAS does inhibit human colon cancer cell NAT activity and gene
      expression.

PMID- 14667467
TI  - Lack of genotoxicity of potassium iodate in the alkaline comet assay and in the
      cytokinesis-block micronucleus test. Comparison to potassium bromate.
AB  - Iodine could be added to the diet of human population in the form of iodide or
      iodate but iodate had not been adequately tested for genotoxicity and
      carcinogenicity. In the present study, genotoxic effects of potassium iodate were
      evaluated in vitro using the alkaline comet assay and the cytokinesis-block
      micronucleus assay on CHO cells and compared to halogenate salt analogues
      potassium bromate and chlorate and also to their respective reduced forms
      (potassium iodide, bromide and chloride). The results showed that the comet assay
      failed to detect the presence of DNA damage after a treatment of cells by
      potassium iodate for concentrations up to 10 mM. This absence of primary DNA
      damage was confirmed in the cytokinesis-block micronucleus assay. In the same
      way, results showed that potassium chlorate as well as potassium iodide, bromide
      and chloride did not induced DNA damage in the alkaline comet assay for doses up
      to 10 mM. By contrast, potassium bromate exposure led to an increase in both DNA
      damage and frequency of micronucleated cells. The repair of bromate-induced DNA
      damage was incomplete 24 h after the end of treatment. These results seem to
      indicate that potassium bromate would induce DNA damage by several mechanisms
      besides oxidative stress.

PMID- 14667468
TI  - Oral (gavage), in utero and postnatal exposure of Sprague-Dawley rats to low
      doses of tributyltin chloride. Part 1: Toxicology, histopathology and clinical
      chemistry.
AB  - Tributyltin (TBT) is a biocide that contaminates foods, especially shellfish. TBT
      is an endocrine disrupter in several marine species and is neurotoxic and
      immunotoxic in mammals. We have examined the effects of exposure to low doses of
      tributyltin chloride (TBTC) from day 8 of gestation until adulthood. Pregnant
      rats were gavaged daily with 0, 0.025, 0.25 or 2.5 mg TBTC/kg body weight from
      day 8 of gestation until weaning. Stomach contents of suckling pups contained
      undetectable levels of TBT and dibutyltin (DBT) levels were detectable only in
      the highest TBTC dose used, indicating negligible lactational transfer to pups.
      Post weaning, pups were gavaged daily with the same dose of TBTC administered to
      their mothers and sacrificed on post-natal days (PND) 30 (males and females), 60
      (females) and 90 (males). TBTC had no effects on dams' body weights, food
      consumption, litter size, sex ratio or survival of pups to weaning. However, all
      doses of TBTC significantly affected parameters of the growth profile of the pups
      (mean body weights, average slope, curvature) and the ratio of weekly food
      consumption to weekly body weight gain indicated enhanced food conversion to body
      mass in females but a decreased conversion in males. Liver, spleen and thymus
      weights were also affected by TBTC. In male pups dosed at 2.5 mg/kg/day, reduced
      serum thyroxine levels were evident, indicating that the thyroid is a target for
      TBTC toxicity. No histopathological lesions were seen in the liver but elevated
      serum alanine aminotransferase, gamma-glutamyl transferase and amylase indicated
      hepatotoxicity. Significant decreases in liver weights in female pups exposed to
      0.025 mg/kg/day TBTC were observed at PND 60. Decreases in spleen and thymus
      weights also pointed towards toxic effects of TBTC on the immune system. The
      0.025 mg/kg/day TBTC should have been a no affect dose and yet this dose caused
      significant effects on growth profiles, decreased liver weights and elevated
      serum GGT levels in females.

PMID- 14667469
TI  - Oral (gavage), in utero and post-natal exposure of Sprague-Dawley rats to low
      doses of tributyltin chloride. Part II: effects on the immune system.
AB  - The immunotoxic effects of tributyltin chloride (TBTC) were examined in the
      offspring of Sprague-Dawley rats exposed in utero from day 8 of gestation,
      through lactation and post-weaning until pups reached the age of 30 days (male
      and female), 60 days (female) and 90 days (male). Daily oral (gavage) doses of
      0.025, 0.25 and 2.5 mg/kg body weight/day were administered in olive oil 7
      days/week. Immunologic endpoints were investigated at the termination of each
      study. Statistically significant results (P<0.05) included the following: At 30
      days, the mean percent and absolute natural killer (NK) cell numbers were
      increased in male and female rats treated with the high TBTC dose. At 60 days,
      female rats had increased mean serum IgM levels at the low and high TBTC doses,
      increased mean percentage CD4(+)8(+) (immature) T lymphocytes at the middle and
      high doses, a non-linear dose-response increase in NK cell activity at the 50:1
      and 100:1 effector:target cell ratios (pairwise comparisons significant at the
      low dose compared with control), and increased mean numbers of L. monocytogenes
      colony-forming bacteria on Day 2 post-infection (significant for trend) and Day 3
      post infection (pairwise comparisons significant only in the middle dose). The 90
      day male rats had decreased mean serum IgA levels at the middle dose group;
      increased IgM levels at the high dose group, increased IgG levels at the middle
      and high doses; decreased IgG2(a) in the high dose compared to the control; a
      dose-related increase in the mean percentage NK cell numbers (pairwise
      comparisons significant at the high dose compared with the control) and increased
      mean NK cell activity (pairwise comparisons significant at all dose groups
      compared with the control). The delayed-type hypersensitivity response to
      oxazolone was increased in the low and middle doses and decreased in the high
      dose. Thymus atrophy was observed in the high TBTC dose across all ages. Thus, in
      utero and post-natal treatment of F1 rats with low levels of TBTC affected some
      aspects of humoral and cell mediated immunity as well as the number and function
      of cells which are involved in the host's immunosurveillance mechanisms against
      tumours and viral infections.

PMID- 14667470
TI  - A comparison of in vitro toxicities of cigarette smoke condensate from Eclipse
      cigarettes and four commercially available ultra low-"tar" cigarettes.
AB  - Eclipse is a cigarette that primarily heats rather than burns tobacco. R.J.
      Reynolds Tobacco Company (RJRT) has previously reported the results of in vitro
      toxicity studies comparing Eclipse with University of Kentucky 1R5F and 1R4F
      reference cigarettes. To characterize the differences between Eclipse and very
      low yielding/ultra low-"tar" (vULT) tobacco-burning cigarettes, RJRT conducted a
      comparative evaluation of the genotoxicity and cytotoxicity of mainstream
      cigarette smoke condensate (CSC) from Eclipse and three vULT tobacco-burning
      cigarettes (Now 83 Box, Merit Ultima and Carlton Soft Pack) as well as the
      leading ultra low-"tar" (ULT) brandstyle (Marlboro Ultra Lights) under four
      smoking regimens: (1) FTC-35 ml puff volume every 60 s for a 2 s duration
      (35/60/2); (2) 50/30/2, 0% vents blocked; (3) Massachusetts-45/30/2, 50% vents
      blocked; (4) Canadian-55/30/2, 100% vents blocked. Ames testing indicated that
      Eclipse CSC was less (P<0.05) mutagenic than CSC from the four cigarettes under
      all smoking regimens when compared on a revertants per mg Total Particulate
      Matter (TPM) basis. When mutagenicity was calculated on a revertants per
      cigarette basis the mutagenicity of Eclipse CSC was lower (P<0.05) than the
      mutagenicity of Merit Ultima, Carlton Soft Pack, and Marlboro Ultra Lights,
      regardless of the puffing regimen. On a per cigarette basis, the calculated
      mutagenicity of Eclipse was higher (P<0.05) than Now 83 Box cigarettes in the FTC
      and 50/30/2 regimens but lower (P<0.05) in the Massachusetts and Canadian
      regimens. Eclipse CSC was less (P<0.05) cytotoxic as measured in the neutral red
      assay (based on EC(50) values-microg TPM/ml media) than the CSC from the four
      test cigarettes regardless of the regimen used. Collectively, these data
      demonstrate that the toxicity of CSC from Eclipse is significantly reduced
      relative to the activity of CSC from the tested vULT cigarettes and the Marlboro
      Ultra Lights.

PMID- 14667471
TI  - Toxicological and metabolic investigations of the safety of N-alpha-lauroyl-L
      arginine ethyl ester monohydrochloride (LAE).
AB  - Studies were conducted to assess the safety of N-alpha-lauroyl-L-arginine ethyl
      ester monohydrochloride, (LAE), a novel food preservative, or Mirenat-N (a 25%
      solution of LAE in propylene glycol). Short term studies demonstrated low acute
      toxicity. LAE was shown to have mild dermal irritation effects but neither LAE
      nor Mirenat-N are skin sensitizers. LAE was demonstrated to be a severe eye
      irritant. In two 13-week feeding studies in rats, systemic NOAELs were
      established for LAE at 15,000 ppm and for Mirenat-N at 50,000 ppm. There were no
      signs of neurotoxicity with LAE after 13-weeks at dietary levels as high as
      50,000 ppm. Embryo-fetal studies with LAE in rats and rabbits showed no
      developmental effects at oral gavage doses up to 2000 and 1000 mg/kg/day for rats
      and rabbits, respectively. NOAELs for systemic maternal effects (reduced food
      intake and body weights in rabbits) were 2000 mg/kg/day for rats and 300
      mg/kg/day for rabbits. In a battery of 5 in vitro genotoxicity tests with LAE or
      Mirenat-N, neither material was observed to have genotoxic (clastogenic or
      mutagenic) activity. Metabolism studies with LAE show that it is rapidly
      metabolized to the amino acid arginine by hydrolysis of the ethyl ester and
      lauroyl amide functions. The arginine subsequently enters the naturally occurring
      urea cycle where it is further metabolized to ornithine and urea and eventually
      to CO(2) through normal mammalian biochemical pathways. The other product of LAE
      cleavage is lauric acid, which is a human dietary component found in many plant
      sources, and as such, would enter into normal fatty acid metabolism.

PMID- 14667472
TI  - Species-specific uncertainty factors for compounds eliminated principally by
      renal excretion in humans.
AB  - An uncertainty factor of 100 is used to derive health-based guidance values for
      human intakes of chemicals based on data from studies in animals. The 100-fold
      factor comprises 10-fold factors for species differences and for interindividual
      differences in response. Each 10-fold factor can be subdivided into toxicokinetic
      and toxicodynamic aspects with a 4.0-fold factor to allow for kinetic differences
      between test species and humans. The current work determined the extent of
      interspecies differences in the internal dose (toxicokinetics) of compounds which
      are eliminated primarily by renal excretion in humans. An analysis of the
      published data showed that renal excretion was also the main route of elimination
      in the test species for most of the identified probe substrates. Interspecies
      differences were apparent for both the mechanism of renal excretion (glomerular
      filtration, tubular secretion and/or reabsorption) and the extent of plasma
      protein binding, both of which may affect renal clearance and therefore the
      magnitude of species differences in the internal dose. For compounds which are
      eliminated unchanged by both humans and the test species, the average differences
      in the internal doses between humans and animals were 1.6 for dogs, 3.3 for
      rabbits, 5.2 for rats and 13 for mice. This suggests that for renal excretion,
      the differences between humans and the rat and especially the mouse may exceed
      the 4.0-fold default factor for toxicokinetics.

PMID- 14667473
TI  - Human variability in the renal elimination of foreign compounds and renal
      excretion-related uncertainty factors for risk assessment.
AB  - Renal excretion is an important route of elimination for xenobiotics and three
      processes determine the renal clearance of a compound [glomerular filtration
      (about 120 ml/min), active renal tubular secretion (>120 ml/min) and passive
      reabsorption (<120 ml/min)]. Human variability in kinetics has been quantified
      using a database of 15 compounds excreted extensively by the kidney (>60% of a
      dose) to develop renal-excretion related uncertainty factors for the risk
      assessment of environmental contaminants handled via this route. Data were
      analysed from published pharmacokinetic studies (after oral and intravenous
      dosing) in healthy adults and other subgroups using parameters relating primarily
      to chronic exposure [renal and total clearances, area under the plasma
      concentration time-curve (AUC)] and acute exposure (Cmax). Interindividual
      variability in kinetics was low for both routes of exposure, with coefficients of
      variation of 21% (oral) and 24% (intravenous) that were largely independent of
      the renal processes involved. Renal-excretion related uncertainty factors were
      below the default kinetic uncertainty factor of 3.16 for most subgroups analysed
      with the exception of the elderly (oral data) and neonates (intravenous data) for
      whom renal excretion-related factors of 4.2 and 3.2 would be required to cover up
      to 99% of these subgroups respectively.

PMID- 14667474
TI  - Lethal and teratogenic effects of naringenin evaluated by means of an amphibian
      embryo toxicity test (AMPHITOX).
AB  - The effect of naringenin on the survival and morphogenesis of amphibian embryos
      was evaluated by means of the AMPHITOX test reporting early life stage and
      chronic toxicity effects. Lethality, malformation incidence and the degree of
      adverse effects were concentration-dependent. The Teratogenic Index (TI) for
      naringenin was 2 pointing out the high developmental hazard of this substance.
      For instance, 10 mg/l naringenin exerted 100% malformations while only 30% of the
      abnormal embryos died. Main abnormalities were reduced body size, axial curves,
      microcephaly, abdominal edema, underdeveloped gills and delayed development.
      Scanning electronic microscopy (SEM) showed alterations in epithelial cell shapes
      related to malformations. The results obtained by means of treatment of Bufo
      arenarum embryos with naringenin from complete operculum stage onwards show that
      at this final stage of development, the susceptibility of the embryos to this
      flavonoid is slightly lower for lethal effects but exerted sublethal adverse
      effects such as transient narcosis, abnormal contortions, loss of equilibrium,
      reduced motility and edema. Overall, amphibian early life stages appeared more
      susceptible to the embryotoxicity associated with exposure to naringenin,
      especially at concentrations greater than 5 mg/l. This increased susceptibility
      may result from the relatively high rates of cellular differentiation and
      morphogenesis that occur at this early stage of development.

PMID- 14667475
TI  - Evaluation of the dermal subchronic toxicity of phenoxyethyl isobutyrate in the
      rat.
AB  - Phenoxyethyl isobutyrate (PEIB) is a fragrance and food ingredient that has been
      granted GRAS status and approved by the FDA for food use. The present studies
      investigated the dermal absorption parameters and subchronic toxicity of PEIB.
      For the absorption, distribution and elimination study, Sprague-Dawley rats
      received a dermal application of 2-[ring U 14C]-PEIB under occlusion for 6 h.
      PEIB was diluted in diethyl phthalate (DEP) to administer, a total application
      volume of 2 ml/kg, concentrations of 0.5, 5 and 50% ( congruent with 10, 100 and
      1000 mg PEIB/kgBW). Approximately 61-69% of the applied dose was recovered from
      the dressing and skin surface washing procedure performed after 6-h exposure. By
      72 h post dose, systemic elimination of radioactivity was congruent with 18 to
      19% of the absorbed dose via the urine with small amounts also found in the feces
      (<1.0%). Terminal (72 h) tissue analysis showed that 0.35-0.72% of the applied
      dose of radioactivity was retained in the carcass with low levels (</=0.03%)
      measured also in the liver, kidney and gastrointestinal tract. Plasma levels
      increased in a dose-related manner, with concentrations equal to 0.02, 0.2 and
      2.0 microg equiv/ml from low to high dose, respectively. The total recovery for
      these studies ranged from 92.2 to 96.2% of the dermally applied radioisotope. In
      a 13-week subchronic rat toxicity study, daily dermal applications of PEIB were
      made under occlusion for 6 h. All groups were dosed at a constant 2 ml/kgBW
      volume of PEIB in the DEP vehicle at concentrations calculated to administer 0,
      100, 300 or 1000 mg PEIB/kgBW/day. Clinical observations, assessments of skin
      irritation, hematology, and blood chemistry, necropsy, and gross and
      histopathologic evaluation of tissues demonstrated no treatment-related effects.
      The local skin irritation and systemic toxicity no-observed-effect-levels (NOELs)
      for PEIB in this study were determined to be >1000 mg/kgBW/day.

PMID- 14667476
TI  - Toxicity of hypercaloric diet and monosodium glutamate: oxidative stress and
      metabolic shifting in hepatic tissue.
AB  - The present study examines the effects of a hypercaloric diet on hepatic glucose
      metabolism of young rats, with and without monosodium glutamate (MSG)
      administration, and the association of these treatments with evaluating markers
      of oxidative stress. Male weaned Wistar rats (21 days old) from mothers fed with
      a hypercaloric diet or a normal diet, were divided into four groups (n=6):
      control (C) fed with control diet; (MSG) treated with MSG (4 mg/g) and control
      diet; (HD) fed with hypercaloric diet and (MSG-HD) treated with MSG and HD. Rats
      were sacrificed after the oral glucose tolerance test (OGTT), at 45 days of
      treatments. Serum was used for insulin determination. Glycogen, hexokinase(HK),
      glucose-6-phosphatase(G6PH), lipid hydroperoxide, superoxide dismutase(SOD) and
      glutathione peroxidase(GSH-Px) were determined in liver. HD rats showed
      hypoglycemia, hyperinsulinemia, and high hepatic glycogen, HK and decreased G6PH.
      MSG and MSG-HD had hyperinsulinemia, hyperglycemia, decreased HK and increased
      G6PH in hepatic tissue. These animals had impaired OGTT. HD, MSG and MSG-HD
      groups had increased lipid hydroperoxide and decreased SOD in hepatic tissue.
      Hypercaloric diet and monosodium glutamate administration induced alterations in
      metabolic rate of glucose utilization and decreased antioxidant defenses.
      Therefore, the hepatic glucose metabolic shifting induced by HD intake and MSG
      administration were associated with oxidative stress in hepatic tissue.

PMID- 14667477
TI  - Safety evaluation of ice-structuring protein (ISP) type III HPLC 12 preparation.
      Lack of genotoxicity and subchronic toxicity.
AB  - Ice-structuring proteins (ISPs) naturally occur in a range of species (including
      edible plants and fish) that need to protect themselves against freeze damage.
      ISPs have potential applications in a number of areas including cryopreservation
      and frozen foods manufacture. However, these materials are not currently
      generally available for commercial use. ISP type III HPLC 12 is of particular
      interest and although it is likely to be consumed naturally, its toxicological
      safety has not previously been assessed. This paper presents data from a set of
      in vitro and in vivo genotoxicity assays (bacterial mutation, chromosome
      aberration, mammalian cell gene mutation and rat bone marrow micronucleus) and a
      3-month repeat-dose gavage study in the rat using high levels of ISP type III
      HPLC 12 preparation produced by recombinant baker's yeast. No evidence was seen
      of a genotoxic potential (using levels accepted as limit concentrations for the
      assays used) or notable subchronic toxicity following oral administration for 3
      months in the rat at up to 580 mg ISP type III HPLC 12/kg/day, the highest dose
      tested (which was considered to be a NOAEL).

PMID- 14667478
TI  - Improving the organisation and delivery of cardiac rehabilitation.

PMID- 14667479
TI  - Multidisciplinary care of heart failure: what have we learned and where can we
      improve?

PMID- 14667480
TI  - Building bridges: the American Heart Association-European Society of Cardiology's
      International Nursing Collaboration.
AB  - This paper described the formal collaboration between the American Heart
      Association's Council on Cardiovascular Nursing and the European Society of
      Cardiology's Working Group on Cardiovascular Nursing. This collaboration
      comprises following dimensions: (1). further expansion on collaboration on annual
      conferences; (2). development of mentoring initiatives; (3). initiation of
      research collaboration; (4). development of joint guidelines; and (5).
      appointment of liaison persons of AHA to ESC and vice versa.

PMID- 14667481
TI  - Perceptions and experiences of heart disease: a literature review and
      identification of a research agenda in older women.
AB  - BACKGROUND: Following diagnosis of heart disease women have poorer health related
      outcomes compared with men. Nursing science lacks well-evaluated interventions to
      address the specific rehabilitative needs of older women with heart disease. This
      paper seeks to inform the development of nursing intervention studies by a review
      of published studies on the experiences and rehabilitative needs of older women
      with heart disease. METHODS: The CINAHL, MEDLINE, FAMILY and PsychINFO databases
      were searched, identifying literature published from 1982 and written in English.
      Keywords used were women, old* (old, older) women, elderly women and: heart
      disease, heart failure, cardiac and rehabilitation. Hand searching of nursing and
      medical textbooks also occurred. These searches resulted in over 120 articles
      that met the criteria of describing experiences, perceptions, psychological
      responses and support rehabilitative needs of older women. RESULTS: Older women
      present with symptoms that are different from those derived from a male-dominated
      research agenda and further there is a paucity of data related to evaluation of
      interventions tailored to the needs of women. Key themes emerging from the
      literature review include not only that older women compared with men have a
      poorer prognosis and experience greater disability moreover they: (1). are at a
      higher risk of psychosocial distress; (2). have a greater need for instrumental
      support and social support; (3). have an altered perception of risk; and (4).
      demonstrate the need for specific rehabilitation programs, tailored to their
      needs. CONCLUSION: Future research should develop and evaluate intervention
      studies that better meet the unique needs of older women with heart disease.
      Particular emphasis needs to be on psychosocial aspects, given evidence that
      identify these are major concerns for women.

PMID- 14667482
TI  - Development and testing of the Cholesterol-Lowering Diet Self-Efficacy Scale.
AB  - A cornerstone of treatment for hypercholesterolemia is dietary therapy. However,
      maintaining adherence to the therapeutic diet has been difficult for patients.
      There is evidence that self-efficacy is a predictor of positive behavior change
      like that involved in or necessary for initiating or maintaining recommended diet
      therapy for cholesterol reduction. This paper reports on two studies guided by
      Bandura's self-efficacy theory. The first study focuses on development and
      initial psychometric evaluation of an instrument measuring self-efficacy for
      adhering to a cholesterol-lowering diet in a sample of 44 cardiac rehabilitation
      patients; the second establishes psychometric properties of the instrument in a
      sample of 228 subjects treated for hypercholesterolemia. In both studies,
      subgroups completed the instrument a second time to provide data on the
      instrument's temporal stability. The Cholesterol-Lowering Diet Self-Efficacy
      Scale consists of 33 statements, some with branches for a total of 56 items. The
      scale measures several components of the eating habits domain related to adhering
      to a cholesterol-lowering eating plan, and shows good reliability and validity.
      Reported self-efficacy is related to prior persistence and past success in
      modifying and maintaining dietary changes, and also to concurrent measures of
      dietary adherence behaviors. The scale is psychometrically sound thus far and
      seems adequate in identifying success in achieving and maintaining a cholesterol
      lowering eating plan.

PMID- 14667483
TI  - Patient's view of heart failure: from the understanding to the quality of life.
AB  - BACKGROUND: Non-pharmacological management is one of heart failure treatment
      cornerstones. Despite its importance several studies showed lack of clinical
      advising by medical staff as well as poor patient compliance to education and
      pharmacological treatment. Hospitalizations and symptoms of heart failure
      negatively influence patients' quality of life. In Slovenia there is a scarcity
      of non-pharmacological management and quality of life data in heart failure
      patients. AIMS: We wanted to obtain data on heart failure patient's quality of
      life and their satisfaction with management of the condition in Slovenia.
      METHODS: During 6 weeks, patients from one university and two community Slovenian
      hospitals were prospectively enrolled to the EuroHeart survey. We invited 415
      patients (mean age 70.6+/-11.4 years, 53% men) to attend an interview 12 weeks
      after the discharge. Out of 415 eligible patients 25 (6%) died during follow up
      period and 187 (45%) attended the interview. Twenty-three percent of them were re
      hospitalized. Vast majority (89%) of interviewed patients were aware of their
      heart condition but only 61% were satisfied with the explanation of their
      clinical condition given by medical staff. On average they were taking 6.3+/-2.3
      drugs. General clinical advice (salt intake 65%, cholesterol or fat intake 63%)
      was more common than specific (daily weighing 35%, avoidance of non-steroidal
      anti-inflammatory drugs 17%). Patients reported high adherence as only 3% of
      given advice were neglected. Symptoms of heart failure were much less common at
      rest than during daily activity (breathlessness in 20% and 78%, fatigue in 18%
      and 81%, respectively). Psychological symptoms as anxiety (70%), depression (50%)
      and stress (48%) were common, as well as cognitive and sleep disturbances, both
      present in more than half of the patients. CONCLUSIONS: Patients with heart
      failure experienced restrictions in quality of life and psychological status. Non
      pharmacological and pharmacological management and patient's satisfaction with
      medical care were below optimal. Educational strategies for medical staff and
      patients as well as organization of an out-patient setting in community hospitals
      are needed.

PMID- 14667484
TI  - Practical application of educational rhetoric: a pathway to expert cardiac nurse
      practice?
AB  - Cardiac nursing takes place within various spheres of health care, reaching into
      primary, secondary and tertiary care within theses, cardiac expertise falls
      within four domains: health promotion, cardiac prevention and rehabilitation,
      acute, chronic and episodic care and palliative care. This paper sets out the
      possibility for a staged development of the cardiac nurse, which could promote
      homogeneity in role, skill and practice. A framework ('Expert Cardiac Nurse
      Pathway') for the United Kingdom, is proposed here, and views on its usefulness
      throughout Europe are sought.

PMID- 14667485
TI  - Health-related quality of life in pacemaker patients: a single and
      multidimensional self-rated health comparison study.
AB  - Since implantation of the first permanent pacemaker in 1958, significant advances
      have been made in pacemaker technology. To date, however, health-related quality
      of life (HRQoL) in a large pacemaker population has not been investigated. With
      dwindling clinical resources, it is important to study HRQoL in a pacemaker
      population in a reliable and straightforward manner. This study aimed to
      determine and compare single and multidimensional self-rated health (SRH) in a
      pacemaker population in terms of sociodemographic characteristics, pacemaker mode
      and symptoms. The findings showed that irrespective of whether the perspective
      was single or multidimensional, this Swedish pacemaker population (n=697) with a
      mean age of 76 years had an acceptable HRQoL. Men, aged 65-84 years, persons who
      were cohabiting, who had their own dwelling, who had a DDD or who had a pacemaker
      for <or=3 and 4-7 years experienced better HRQoL. Efforts need to be made for
      women, single persons, the elderly and retired persons. In conclusion, the SRH of
      a pacemaker population can be trustworthy established by means of a single
      dimensional SRH question.

PMID- 14667486
TI  - 'Grasp life again'. A qualitative study of the motive power in myocardial
      infarction patients.
AB  - Myocardial infarction is the most common cause of death in Sweden today and is
      responsible for approximately 30% of all deaths. The aim of this study was to
      obtain increased knowledge and understanding of what motive power is and how it
      affects the individual's rehabilitation and return to a functioning daily life.
      Thirteen patients, six females and seven males, who had experienced a myocardial
      infarction, aged between 39 and 72 years and with a minimum interval from
      myocardial infarction diagnosis of at least 12 months, were interviewed. Grounded
      theory was the method used for data collection and analysis, since the method is
      focusing on social processes and interaction. The analysis process identified
      motive power as a core category: zest for life. The participants expressed a
      desire and a longing to continue living. The participants' experiences of their
      disease as well as being discharged from hospital forced them to reorientation.
      Autonomy, the individual's own active decision-making, plays a significant role
      in this zest for life. Care for was identified as the support base for zest for
      life. As health-care professionals we must, at a very early stage on the ward,
      form an idea of what kind of patient we have in front of us.

PMID- 14667487
TI  - Parental influence on models of primary prevention of cardiovascular disease in
      children.
AB  - BACKGROUND: Lifestyle behaviors such as overeating and physical inactivity
      contribute significantly to CVD, the leading cause of morbidity and mortality
      among adults globally. CVD risk factors that begin in children often track into
      adulthood. Parents are believed to influence the health behaviors of their
      children. OBJECTIVE: To review the literature on parental influence on children's
      health beliefs and behaviors, particularly eating and exercise behaviors as
      indicators of CV health, school-based CVD risk reduction programs, and
      racial/ethnic, gender and socioeconomic considerations for models of primary
      prevention of CVD in children. METHODS: Seventeen studies that included parents
      as either a source of information, change agent or participant in a CVD risk
      reduction intervention were identified searching the Medline, CINAHL and PsycINFO
      databases from 1980 through 2002. RESULTS: Children's lifestyle health beliefs
      and behaviors are significantly influenced by positive parental modeling and
      involvement in exercise and healthy eating; parental influence on children's
      behavior lasts beyond adolescence; parents are effective teachers of health
      habits at home when prompted by health educators; and parental influences vary by
      ethnicity/race, socioeconomics and gender. CONCLUSIONS: A broader base of
      knowledge that is socioculturally sensitive must be developed about what parents
      and children believe is healthy, how parents model beliefs and behaviors for
      their children, and how to build self-efficacy for positive health behaviors.

PMID- 14667488
TI  - Adherence to long-term therapies: evidence for action.

PMID- 14667489
TI  - [Re symposium: "Approaches to optimize the discovery of CNS receptor imaging
      probes for use in drug discovery and development"].

PMID- 14667490
TI  - Predicting the success of a radiopharmaceutical for in vivo imaging of central
      nervous system neuroreceptor systems.
AB  - In vivo imaging of the central nervous system (CNS) neuroreceptors in humans
      began was used in the early 1980s. Now, some twenty years later, the success of
      radiopharmaceutical imaging is still often one based on empiricism and
      serendipity. Nevertheless, a number of factors can be identified based on the
      robot experience in developing these radiotracers. This article will describe
      some of the issues that may be useful in choosing approaches to radiolabel
      ligands as future imaging agents of neuroreceptors, transporters and
      intrasynaptic measures of neurotransmitters. A description of the current process
      from hypothesis to radiochemical preclinical development, non-human primate
      imaging development of quantitative procedures finally leading to toxicology,
      dosimetry and eventually human applications are provided. The role of important
      factors including metabolism and lipophilicity, affinity and other factors for
      optimizing radiolabeling strategies is dealt with. Furthermore, issues involving
      decision making of how far to extend efforts in developing a radiotracer and when
      might be an appropriate stopping place are discussed. Finally some typical
      examples of the use of these radiotracers, especially with emphasis on stable
      drug design and development, are provided. These include occupancy studies and
      mechanism of action studies. In summary, the prediction of tracer success
      includes: first, identification of appropriate targets and precursors, then
      systematic optimization of ligands with continuous feedback from pharmacokinetics
      and iterative improvement based on unsuccessful tracers. This article is intended
      to present a pragmatic overview of the radiopharmaceutical development process
      with emphasis on the CNS.

PMID- 14667491
TI  - Relationships between radiotracer properties and image quality in molecular
      imaging of the brain with positron emission tomography.
AB  - In molecular imaging of the brain, many factors affect the reliability of the
      quantitative information that can be derived from the imaging process. This
      article discusses factors impacting on the imaging quality that are related to
      the radiotracer per se. Following a brief summary of key concepts in receptor
      quantification, a number of these factors are discussed, including selectivity,
      affinity, delivery, and lipophilicity. Concepts discussed in the theoretical
      section are then illustrated, by reviewing a recent comparative evaluation of
      four agents developed to label the serotonin transporter ([(11)C]ADAM,
      [(11)C]DASB, [(11)C]DAPA, and [(11)C]AFM). Specifically, the relationship between
      affinity and lipophilicity, measured in vitro, and several scanning parameters
      are investigated. These include peripherical metabolism, brain uptake, required
      scanning time, nonspecific binding, and binding potential. It is shown that,
      within a given structural family, affinity and lipophilicity are associated with
      scan outcome in a relatively predictable manner.

PMID- 14667492
TI  - Determination of lipophilicity and its use as a predictor of blood-brain barrier
      penetration of molecular imaging agents.
AB  - Compound lipophilicity is a fundamental physicochemical property that plays a
      pivotal role in the absorption, distribution, metabolism, and elimination (ADME)
      of therapeutic drugs. Lipophilicity is expressed in several different ways,
      including terms such as Log P, clogP, delta Log P, and Log D. Often a parabolic
      relationship exists between measured lipophilicity and in vivo brain penetration
      of drugs, where those moderate in lipophilicity often exhibit highest uptake.
      Reduced brain extraction of more lipophilic compounds is associated with
      increased non-specific binding to plasma proteins. More lipophilic compounds can
      also be more vulnerable to P450 metabolism, leading to faster clearance. Very
      polar compounds normally exhibit high water solubility, fast clearance through
      the kidneys, and often contain ionizable functional groups that limit blood-brain
      barrier (BBB) penetration. The brain penetration and specific to non-specific
      binding ratios exhibited in vivo by positron emission tomography (PET) and single
      photon emission computed tomography (SPECT) radiotracers involves a complex
      interplay between many critical factors, including lipophilicity, receptor
      affinity, metabolism, molecular size and shape, ionization potential, and
      specific binding to BBB efflux pumps or binding sites on albumin or other plasma
      proteins. This paper explores situations in which lipophilicity is a good
      predictor of BBB penetration, as well as those where this correlation is poor.
      The more commonly used methods for measuring lipophilicity are presented, and the
      various terms often found in the literature outlined. An attempt is made to
      describe how this information can be used in optimizing the development of PET
      and SPECT tracers that target the central nervous system (CNS).

PMID- 14667493
TI  - Autoradiography with positron emitting isotopes in positron emission tomography
      tracer discovery.
AB  - Rapid development of labeling chemistry and generation of new chemical entities
      for biologic interactions via combinatorial chemistry and high throughput
      screening gives great potential for the development of new positron emission
      tomography (PET) tracer candidates. It must, however, be realized that a large
      fraction of these candidates will fail to characterize the desired biochemistry
      in vivo due to undesirable properties that are not relevant to providing a
      specific signal in vitro. A full characterization of a PET tracer is a lengthy
      and expensive procedure, and it is necessary to establish confidence via a number
      of assays that a tracer will provide useful data in the target species (generally
      human). These assays should also serve as a background to choose or to reject a
      tracer at an early time point, conserving valuable resources and time.
      Autoradiography performed as an ex vivo binding technique or as ex vivo recording
      of in vivo tracer distribution are, in this respect, very important tools.
      Autoradiography binding methods allow a range of frozen tissues to be sectioned
      and incubated with the PET tracer, and with due caution and controls with
      selective blockade of binding, quantitative values can be obtained with respect
      to tracer binding and its regional distribution. The method is easy to learn and
      set up, and should be included in all PET research and development labs. Ex vivo
      autoradiography of selected organs or whole animals gives qualitative images of a
      tracer's distribution with high resolution and is especially valid for 18F
      labeled tracers. When tracer administration is not limited by mass due to
      specific radioactivity, 11C-tracers can also be readily used. This method is
      attractive to use as a complement to small animal imaging due to its high
      resolution and anatomical correlate. Living slice autoradiography is a more
      cumbersome method, but has an advantage of utilizing live tissue that retains
      certain metabolic functions. The use of these different methods in the validation
      of tracers and for supplying complementary information is illustrated.

PMID- 14667494
TI  - Application of LC-MS to the analysis of new radiopharmaceuticals.
AB  - Liquid chromatography in combination with mass spectrometry (LC-MS) is key to the
      identification of metabolites in new molecular imaging probes. These metabolites
      can be generated using hepatocytes from various species in vitro. Metabolites
      produced from 4-fluoro-N-[2-[4-(2-methoxylphenyl)piperazino]ethyl]-N-(2
      pyridyl)cyclohexane carboxamide (FCWAY) using rat and human hepatocytes are
      different, whereas metabolites from (3-(3-fluoropropylthio)-1,2,5-thiadiazol-4
      yl)-tetrahydro-l-methyl-pyridine (FP-TZTP) using rat and human hepatocytes were
      similar. The combination of LC-MS and hepatocytes are an indispensable tool in
      the development of new molecular imaging probes.

PMID- 14667495
TI  - 2-Dialkylamino-6-acylmalononitrile substituted naphthalenes (DDNP analogs): novel
      diagnostic and therapeutic tools in Alzheimer's disease.
AB  - This article presents a comprehensive review of the in vitro and in vivo
      detection of neurofibrillary tangles (NFTs) and beta-amyloid senile plaques
      (SPs), neuropathological lesions found in the brains of the Alzheimer's disease
      (AD) patients, using FDDNP and its analogs. FDDNP and its analogs have excellent
      ability to bind to NFTs and SPs in vitro as shown by binding assays, confocal
      fluorescence microscopy with stained AD brain tissue and digital autoradiography
      with [18F]FDDNP. [18F]FDDNP-PET molecular imaging permits detection of these
      pathologies in living subjects. The discovery of a new binding site to Abeta(1
      40) fibrils as a result of FDDNP binding also opens a therapeutic opportunity for
      early treatment of Alzheimer's disease. FDDNP shares a previously unrecognized
      common binding site on Abeta(1-40) fibrils and senile plaques with non-steroidal
      anti-inflammatory drugs (NSAIDs) (e.g., naproxen and ibuprofen). Naproxen,
      ibuprofen and even FDDNP significantly inhibit aggregation of the Abeta(1-40)
      peptide in the micromolar range. This new binding site on Abeta(1-40) fibrils
      also offers a molecular template for design of anti-aggregation drugs without the
      secondary effects of NSAIDs. Therefore it is anticipated that a new vision for
      prevention, early diagnosis and treatment of Alzheimer's disease would be rapidly
      developing.

PMID- 14667496
TI  - Iodinated tracers for imaging amyloid plaques in the brain.
AB  - Excessive amounts of protein deposits, beta-amyloid (Abeta) plaques, are commonly
      detected in the postmortem brains of Alzheimer's disease (AD) patients. These
      Abeta plaques are believed to play an important role in the pathogenesis of the
      disease. Development of Abeta plaque-specific imaging agents for detecting and
      monitoring the changes of Abeta plaque deposition in living brains are reported.
      These agents, if successfully developed, may serve as potential biomarkers for
      the disease. Several iodinated derivatives based on variety of core structures
      are labeled with radioiodine as single photon emission computed tomography
      (SPECT) imaging agents. Thioflavin (or benzothiazole) derivatives displayed
      excellent in vitro characteristics with high binding affinities for Abeta
      aggregates (in subnanomolar to nanomolar range) and excellent plaque labeling of
      AD brain sections. However, the in vivo kinetic properties appeared unfavorable
      for further development. A novel series of imidazo-pyridine derivative, such as 2
      (4'-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine (IMPY), exhibited highly
      desirable in vivo properties. Additional structural modification resulting in
      stilbene derivatives displayed good binding affinities for Abeta aggregates. In
      addition, fluorene compounds with a rigid tricyclic structure showed in vitro and
      in vivo characteristics as potential SPECT imaging agents. Criteria for selection
      of radioiodinated tracers with suitable in vivo properties to detect amyloid
      plaques are discussed.

PMID- 14667497
TI  - Homeobox genes and cancer: new OCTaves for an old tune.
AB  - In this issue of Cancer Cell, Gidekel et al. demonstrate that Oct-4, a member of
      the POU class of homeobox genes, is a critical player in the genesis of
      testicular germ cell tumors. This study provides further evidence that
      deregulated expression of homeobox genes, which occurs in many solid tumors, is
      functionally relevant for carcinogenesis and highlights unique features that
      distinguish homeobox genes from other cancer-promoting genes.

PMID- 14667498
TI  - Tumor vasculature address book: identification of stage-specific tumor vessel zip
      codes by phage display.
AB  - Using in vivo phage display technology with murine tumorigenesis models, two
      reports have identified peptide motifs that selectively home to distinct
      molecular vascular targets in a tumor type- and stage-specific manner (Hoffman et
      al., 2003 and Joyce et al., 2003 [this issue of Cancer Cell]). By probing the
      surface-protein repertoire of these unique vascular beds, a pioneering draft of a
      molecular roadmap to decipher the heterogeneity of the vascular system in the
      context of carcinogenic progression has been plotted. Analysis of these phage
      peptides that differentially home to dysplastic or invasive tumor vasculature
      will lay the foundation for identifying unique functional tumor vascular-specific
      motifs that could potentially be applied to targeted therapeutic and imaging
      modalities.

PMID- 14667499
TI  - Modeling transformation and metastasis in Drosophila.
AB  - Transformation and metastasis are complex, multistep processes. Two recent papers
      exploit powerful Drosophila genetics techniques to explore cooperation between
      multiple genetic manipulations and to model these processes. In particular,
      oncogenic Ras is found to collaborate with disruption of cell polarity to trigger
      massive neoplasia and metastasis. These studies promise further progress in
      research into the causes of cancer.

PMID- 14667500
TI  - Advancing the field of drug delivery: taking aim at cancer.
AB  - Drug delivery systems for cancer therapeutics have now been used by millions of
      patients and have resulted in the creation of new therapies as well as
      significantly improving existing ones. Here we discuss a number of the drug
      delivery systems that have been approved by regulatory authorities and that are
      currently in clinical use, such as controlled delivery of cancer therapeutics,
      local chemotherapy, polymer drug conjugates, liposomal systems, and transdermal
      drug delivery patches. The next generation of "smart" drug delivery approaches
      such as controlled release microchips are discussed as are some of the future
      challenges and directions in this field.

PMID- 14667501
TI  - Will mTOR inhibitors make it as cancer drugs?

PMID- 14667502
TI  - Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in
      hematopoietic tissue.
AB  - Wnt5a is a member of the Wnt family of secreted glycoproteins that play essential
      organizing roles in development. Similar to other Wnt members, Wnt5a can
      upregulate cell proliferation and has been proposed to have oncogenic function.
      Here we report that Wnt5a signals through the noncanonical Wnt/Ca++ pathway to
      suppress cyclin D1 expression and negatively regulate B cell proliferation in a
      cell-autonomous manner. Wnt5a hemizygous mice develop myeloid leukemias and B
      cell lymphomas that are clonal in origin and display loss of Wnt5a function in
      tumor tissues. Furthermore, analysis of human primary leukemias reveals deletion
      of the WNT5A gene and/or loss of WNT5A expression in a majority of the patient
      samples. These results demonstrate that Wnt5a suppresses hematopoietic
      malignancies.

PMID- 14667503
TI  - Oct-3/4 is a dose-dependent oncogenic fate determinant.
AB  - The Oct-3/4 transcription factor sustains embryonic stem (ES) cell self-renewal
      and is a dose-dependent cell fate determinant. In the adult male, its expression
      is restricted to type A spermatogonia. We show that Oct-3/4 is expressed in all
      human testicular germ cell tumors (GCTs) tested, even in the early premalignant
      component. We demonstrate that Oct-3/4 dictates ES cells' oncogenic potential in
      a dose-dependent manner; high levels increase the malignant potential of ES cell
      derived tumors while Oct-3/4 inactivation induces regression of the malignant
      component. Oct-3/4 expression in a heterologous cell system transforms
      nontumorigenic cells and endows tumorigenicity in nude mice. Our findings suggest
      that Oct-3/4 is not only a distinctive immunohistochemical marker for GCTs, but
      also plays a critical role in the genesis of these tumors.

PMID- 14667504
TI  - Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of
      transcription.
AB  - Recent efforts to develop pharmacologic agents that restore function to mutant
      forms of p53 hold significant promise in cancer therapy. Here, we examine the
      effects of such pharmacologic activation of p53 function using a small molecule,
      PRIMA-1, and a model system employing a p53 protein fused to a mutant steroid
      binding domain of the murine estrogen receptor (p53ERtam) that renders it
      responsive only in the presence of 4-hydroxytamoxifen. In either case, p53
      activation triggered apoptosis that was not inhibited by the presence of
      macromolecular synthesis inhibitors. This p53-induced, transcription-independent
      apoptosis is Bax dependent, proceeds in the absence of a nucleus, and involves
      Bax translocation and cytochrome c release. Hence, pharmacologic p53 modulators
      can activate a transcription-independent apoptotic program.

PMID- 14667505
TI  - Progressive vascular changes in a transgenic mouse model of squamous cell
      carcinoma.
AB  - Phage display was used to identify homing peptides for blood vessels in a mouse
      model of HPV16-induced epidermal carcinogenesis. One peptide, CSRPRRSEC,
      recognized the neovasculature in dysplastic skin but not in carcinomas. Two other
      peptides, with the sequences CGKRK and CDTRL, preferentially homed to
      neovasculature in tumors and, to a lesser extent, premalignant dysplasias. The
      peptides did not home to vessels in normal skin, other normal organs, or the
      stages in pancreatic islet carcinogenesis in another mouse model. The CGKRK
      peptide may recognize heparan sulfates in tumor vessels. The dysplasia-homing
      peptide is identical to a loop in kallikrein-9 and may bind a kallikrein
      inhibitor or substrate. Thus, characteristics of the angiogenic vasculature
      distinguish premalignant and malignant stages of skin tumorigenesis.

PMID- 14667506
TI  - Stage-specific vascular markers revealed by phage display in a mouse model of
      pancreatic islet tumorigenesis.
AB  - The vasculature in the angiogenic stages of a mouse model of pancreatic islet
      carcinogenesis was profiled in vivo with phage libraries that display short
      peptides. We characterized seven peptides distinguished by their differential
      homing to angiogenic progenitors, solid tumors, or both. None homed appreciably
      to normal pancreatic islets or other organs. Five peptides selectively homed to
      neoplastic lesions in the pancreas and not to islet beta cell tumors growing
      subcutaneously, xenotransplant tumors from a human cancer cell line, or an
      endogenously arising squamous cell tumor of the skin. Three peptides with
      distinctive homing to angiogenic islets, tumors, or both colocalized with markers
      that identify endothelial cells or pericytes. One peptide is homologous with pro
      PDGF-B, which is expressed in endothelial cells, while its receptor is expressed
      in pericytes.

PMID- 14667507
TI  - The t(1;3) breakpoint-spanning genes LSAMP and NORE1 are involved in clear cell
      renal cell carcinomas.
AB  - By positional cloning, we identified two breakpoint-spanning genes in a familial
      clear cell renal cell carcinoma (CCRCC)-associated t(1;3)(q32.1;q13.3): LSAMP and
      NORE1 (RASSF1 homolog). Both genes are downregulated in 9 of 9 RCC cell lines.
      While the NORE1A promoter predominantly presents partial methylation in 6 of the
      cell lines and 17/53 (32%) primary tumors, the LSAMP promoter is completely
      methylated in 5 of 9 cell lines and in 14/53 (26%) sporadic and 4 familial
      CCRCCs. Expression of LSAMP and NORE1A proteins in CCRCC cell lines inhibited
      cell proliferation. These characteristics indicate that LSAMP and NORE1A may
      represent new candidate tumor suppressors for CCRCC.

PMID- 14667509
TI  - Smart drugs in prostate cancer.
AB  - OBJECTIVES: Growth signaling is instrumental in tumor development. Insight into
      signaling pathways by molecular and cellular biology has changed the development
      of new anticancer agents. Outside the field of urology specifically targeted
      drugs such as imatinib mesylate and gefitinib showed impressive anticancer
      activity in chronic myeloid leukemia and non-small cell lung cancer,
      respectively. METHODS: Literature search of PubMed documented publications and
      abstracts from meetings. RESULTS: Preclinical data in prostate cancer shows
      upregulation of a wide variety of growth factors and their receptors such as
      PDGF, EGF, IGF, FGF, and VEGF suggesting efficacy of agents targeting these
      pathways. Here the preclinical evidence and first clinical data on the use of
      growth signal targeting in prostate cancer is reviewed. Although some anticancer
      efficacy of signal transduction inhibition monotherapy was reported, combination
      with chemotherapy and radiotherapy seemed most promising in prostate cancer.
      CONCLUSION: So-called smart drugs are small molecules targeted at specific growth
      signaling pathways. These new drugs will dominate clinical trials in the years to
      come either as single-drug modality, but more likely as combination treatment.

PMID- 14667510
TI  - Lymphoedema in urological cancer.
AB  - OBJECTIVES: To review the evidence underlying the diagnosis, pathology and
      treatment of lymphoedema of the lower extremities and genitalia from or following
      the treatment for urological cancer, and to suggest possible underlying
      pathophysiological mechanisms that may explain its development. METHODS: Reviews
      of the epidemiological, surgical, and scientific literature and personal
      experience of treatment of patients are used to build a picture of clinical
      setting and the physiological principles underlying lymphoedema of the leg.
      RESULTS: Lymphoedema of the leg and genitals results in serious morbidity for the
      patient. The incidence is largely unknown, but varies according to the type and
      location of tumours and may be up to 50% in advanced stages of penile carcinoma,
      or following its treatment. Although the aetiology of the condition is either
      iatrogenic, or associated with malignancy, the underlying pathophysiology is not
      well understood. CONCLUSIONS: Recent studies in breast cancer related lymphoedema
      point to underlying vascular as well as lymphatic problems, but the parallels
      with lower limb lymphoedema are not known.

PMID- 14667511
TI  - Role of bisphosphonates in prostate cancer.
AB  - OBJECTIVE(S): To investigate the role of bisphosphonates in the long-term
      supportive care of patients with prostate cancer, an emerging medical challenge.
      Although the success of current therapeutic options has extended the survival of
      patients with prostate cancer, they often develop skeletal morbidity from disease
      and treatment-related effects that undermine skeletal integrity. METHODS: Studies
      were identified through MEDLINE searches, review of bibliographies of relevant
      articles, and review of abstracts from scientific meetings. RESULTS: Low bone
      mass is prevalent in patients in early stages of prostate cancer, although the
      reasons for this correlation are unknown. Furthermore, androgen deprivation
      therapy (ADT) by either pharmaceutical (including hormonal) or surgical
      castration causes significant decreases in bone mineral density. Pamidronate has
      been shown to prevent bone loss, whereas zoledronic acid has been shown to
      increase bone mass in men undergoing ADT. Finally, zoledronic acid is the only
      bisphosphonate that has demonstrated efficacy in reducing objectively measurable
      skeletal complications in patients with bone metastases secondary to prostate
      cancer. CONCLUSION: Bisphosphonates, zoledronic acid in particular, have potent
      activities against osteoclasts, which affect bone integrity. Zoledronic acid has
      now become an additional option that can provide benefits to patients with
      prostate cancer throughout the course of their disease.

PMID- 14667512
TI  - pT0 after radical prostatectomy: overtreatment for insignificant prostate cancer?

PMID- 14667513
TI  - Pathological T0 prostate cancer without neoadjuvant therapy: clinical
      presentation and follow-up.
AB  - INTRODUCTION AND OBJECTIVES: Radical prostatectomy is a standard therapy for
      patients with prostate cancer diagnosed by prostatic needle biopsy, prostate
      cytology, transurethral resection of the prostate or prostatectomy. In a small
      group of patients no tumour can be found in the radical prostatectomy specimen.
      These cases are classified as stage pT0. The aim of this study was to evaluate
      the clinical presentation of this entity and their prognosis. MATERIAL AND
      METHODS: In a nation-wide database the clinical data of 3609 patients with
      prostate cancer were collected. 28 patients (0.8%) were staged as pT0 in the
      radical prostatectomy specimen. The data included age, prostate specific antigen
      (PSA), and pathological report at diagnosis, histology of the radical
      prostatectomy specimen and follow-up data. RESULTS: The diagnosis was made by
      TURP (transurethral resection of the prostate) in 15, prostatectomy in 2, needle
      biopsy in 11, and cytology in 2 patients. For patients who underwent TURP or
      prostatectomy the preoperative staging was T1a in 10 and T1b in 5 cases. 12
      patients diagnosed by biopsy or cytology were classified T2a and one patient
      after biopsy as T2b. 9 patients had a GI- and 19 a GII-tumour, GIII-pattern was
      not represented. The mean age at diagnosis was 64.7 years (range 53-79 years).
      The PSA at the time of diagnosis was <4ng/ml in 8 cases; 4-10ng/ml in 16 cases
      and >10ng/ml in 4 patients. One patient presented with a micrometastasis in a
      single lymph node. Median follow-up was 62 months (19-150). All patients had
      undetectable PSA levels following surgery. No patient presented with clinical or
      biochemical progression. One patient died with no evidence of disease at 133
      months after radical prostatectomy. CONCLUSIONS: None of the clinical parameters
      had a strong association with a pathologically proven T0 situation after radical
      prostatectomy in this setting. Interestingly no patient had a high-grade tumour.
      None of the patients classified as pT0 had a biochemical or clinical relapse
      during follow-up.

PMID- 14667514
TI  - Prognosis of stage pT0 after prolonged neoadjuvant endocrine therapy of prostate
      cancer: a matched-pair analysis.
AB  - OBJECTIVES: Stage pT0 following prolonged neoadjuvant endocrine therapy (PPNET)
      of prostate cancer is of great clinical interest, because this finding suggests
      maximum tumor damage. Therefore pT0 patients are expected to have an extremely
      favorable PSA progression rate. The purpose of this study was to assess whether
      the PSA progression rate of pT0 patients after PPNET is lower than that of non
      pT0 patients after PPNET. METHODS: 174 patients with previously untreated,
      clinical stage cT1-3 carcinomas were submitted to PSA monitored complete androgen
      deprivation therapy followed by radical prostatectomy (RP). In 138 patients the
      RP specimens showed residual cancer, in 36 patients no residual cancer was found.
      Biochemical progression was defined as PSA >/=0.2ng/ml. To control for
      confounding prognostic factors (Gleason score, cT-stage) between both groups a
      matched-pair analysis for the cumulative risk of biochemical failure was
      performed, resulting in 30 matched pairs. RESULTS: With a median follow-up of
      37.9 and 46.0 months in the matched non-pT0 and pT0 cohort respectively, matched
      pair analysis failed to demonstrate significant differences in crude PSA relapse
      free survival between both groups (p=0.7758). CONCLUSION: The results suggest
      that patients converted into pT0 after PPNET do not represent a subgroup with an
      extremely favorable prognosis. However our results have to be confirmed by the
      assessment of larger cohorts of pT0 patients with a longer follow-up. The
      presented data do not allow drawing any conclusions on the prognostic impact of
      PPNET in general.

PMID- 14667515
TI  - Cyclooxygenase-2 expression in bladder cancer: correlation with poor outcome
      after chemotherapy.
AB  - OBJECTIVES: Cycylooxygenase-2 (Cox-2) has been shown to play a significant role
      in the carcinogenesis of various human tumours. Recent experimental work suggests
      that Cox-2 expression may reduce the cytotoxic effects of chemotherapy and
      radiation therapy. We examined Cox-2 expression in bladder cancer and its
      relationship to clinicopathologic factors, survival data, and outcome in patients
      receiving cisplatin-based chemotherapy. METHODS: In 157 patients after cystectomy
      for bladder cancer, Cox-2 was assessed immunohistochemically; 62 patients had
      received chemotherapy, either adjuvant or for metastatic disease. Results were
      correlated with clinical data, survival and outcome of chemotherapy. RESULTS: Cox
      2 expression was present in 131 patients (83.4%). Expression did not correlate
      with tumour stage and histologic grade, but was significantly related to
      histologic subtype (TCC vs. SCC, p=0.038). Survival analysis showed no relation
      between Cox-2 expression and overall and disease-free survival; however, in the
      subgroup of 62 patients who received chemotherapy, strong Cox-2 expression
      significantly correlated with poor overall survival (p=0.01). CONCLUSIONS: High
      expression of Cox-2 in bladder cancer patients receiving chemotherapy was
      significantly associated with shorter survival. Further studies are warranted to
      clarify if combining chemotherapy with Cox-2-inhibition has an impact on response
      and survival rates.

PMID- 14667516
TI  - Frequency, clinical presentation and evolution of renal oncocytomas: multicentric
      experience from a European database.
AB  - OBJECTIVES: To understand the clinical behavior of renal oncocytoma in a
      retrospective analysis of a European multicentric nephrectomies database.
      METHODS: The records of 891 patients who underwent surgical resection of renal
      neoplasm were reviewed. Relevant clinical and pathological data for each patient
      were retrieved in a database. RESULTS: Thirty-two (3.6%) cases of renal
      oncocytoma were identified. Twenty patients (62.5%) were asymptomatic. No case of
      lymphatic invasion or metastatic disease, nor any evidence of vascular or fat
      tissue invasion was found. Thirty-one cases (96%) exhibited low mitotic activity.
      In one case the presence of renal clear cell carcinoma (diameter: 1.5cm) was
      found. After a median follow-up of 42 months, 87.5% of patients were alive with
      no evidence of tumor, while 9.3% of patients had died for non-malignant causes.
      One patient had not treated the tumor surgically and was disease-free at a 27
      month follow-up. CONCLUSIONS: Renal oncocytoma is a benign neoplasm,
      characterized by slow growth and excellent prognosis after surgery. Nephron
      sparing techniques may be adequate for tumor removal.

PMID- 14667517
TI  - Impact on active scope deflection and irrigation flow of all endoscopic working
      tools during flexible ureteroscopy.
AB  - OBJECTIVE: Flexible ureteroscopy is nowadays an alternative effective option for
      treatment of upper urinary tract stones, especially in the lower renal pole.
      Access in this case is often limited by active deflection capabilities of the
      instrument which is always deteriorated by the passage of different tools through
      the working channel. Insertion of them limits also the irrigation flow and so
      that the visibility. These deteriorations vary largely following the tool
      inserted. We performed an in vitro evaluation of deterioration of active
      deflection, possibility of tool insertion in maximal active deflection and
      irrigation flow in 6 different flexible ureteroscopes with almost all of tools
      available. METHODS: A total of 546 measures of maximal deflection, test of
      passage of tools in maximal deflection and measures of irrigation flow passage
      through the working channel were made on 6 different ureteroscopes, the ACMI DUR
      8, the ACMI DUR-8 "Elite", the Karl Storz 11274 AA, the Karl Storz 11278 AU1
      "Flex-X", the Wolf 7325.172 and the Olympus URF/P-3 without any tool inserted and
      with 22 different tools (14 extraction devices and 8 lithotripsy probes).
      RESULTS: Larger caliber tools resulted in more deflection degradation than
      smaller ones but it is more evident in case of use of non-nitinol tools instead
      of the nitinol ones. Generally lithotripsy probes affected active deflection more
      than nitinol extractions tools but different brand laser fibres present different
      results. Usually 1.6 and 1.9F electro hydraulic probes offer a slightly better
      deflection than does the 200micro laser fibre. Ballistic shock probes are so
      stiff that can not be used for treating lower renal pole stones. CONCLUSIONS: An
      array of different instruments are nowadays available for upper renal endoscopic
      treatment but they differ largely on stiffness and on obstruction to irrigation
      flow. Laser probes are very problematic to insert in the already deflected
      instruments, something that is less evident with the EHL probes and the smaller
      nitinol extraction tools. Irrigation flow is inversely proportional to the
      diameter of the tool inserted. Tools with a diameter of 3 French or more block
      totally the flow.

PMID- 14667518
TI  - Peripheral afferent nerve stimulation for treatment of lower urinary tract
      irritative symptoms.
AB  - OBJECTIVES: To assess the efficacy of posterior tibial nerve stimulation for
      treatment of lower urinary tract irritative symptoms (urgency, frequency, urge
      incontinence and pelvic pain). PATIENTS AND METHODS: 51 female patients with a
      mean age of 55 years were enrolled in the study. The patients presented with the
      following symptoms: Frequency/urgency 26 patients (50.98%), urge incontinence 22
      (43.13%) and interstitial cystitis 3 patients (5.88%). The technique consists in
      administering low voltage electric stimulation via a 3-5cm needle placed above
      the tibial malleolus. Patients received weekly stimulations of 30 minutes for a
      10-week period. Quality of life questionnaires and voiding diaries before and
      after treatment were completed. Moreover, the results were evaluated by patients.
      The variables analysed include: daytime and nighttime voiding frequency, daytime
      and nighttime voiding volume, daytime and nighttime leakage episodes and
      hypogastric pain. RESULTS: A statistically significant improvement was seen in
      all variables, especially remarkable in relation to frequency/urgency, impact on
      women quality of life and hypogastric pain, being less marked in relation to
      leakage episodes and voiding volume. CONCLUSIONS: Afferent nerve stimulation
      offers an alternative treatment for managing lower urinary tract irritative
      symptoms. However, it would be advisable to confirm the results obtained by means
      of long-term randomized, follow-up studies.

PMID- 14667519
TI  - Neuroselective current perception threshold evaluation of bladder mucosal sensory
      function.
AB  - OBJECTIVE: To evaluate human bladder mucosal sensory function by neuroselective
      Current Perception Threshold (CPT) measures from healthy and neuropathic
      bladders. METHODS: Eight healthy volunteers and 38 patients with urinary symptoms
      underwent conventional urodynamic tests including water-filling cystometry and
      ice water test. Standardized neuroselective CPT measures were obtained from the
      left index finger and the mucosa of the posterior bladder wall. Three different
      CPTs were obtained from each test site using a constant alternating current
      sinusoid waveform electrical stimulus presented at 2000Hz, 250Hz and 5Hz
      stimulation frequencies, which could selectively reflect the functions of the
      large myelinated fibers (A-beta-fiber), the small myelinated fibers (A-delta
      fiber), and the unmyelinated fibers (C-fiber), respectively. RESULTS: As the
      determination of CPT values on the finger skin, the CPT values in the bladder
      could be determined using the neuroselective measures in all patients but three
      who had no sensory response (absence of sensation) caused by complete spinal
      injury. In the 8 patients with detrusor hyperreflexia due to incomplete spinal
      cord injury (supra-sacral lesion), the bladder CPT value (4.0+/-1.9) at 5Hz was
      significantly lower (p<0.01) than that in the controls (26.2+/-17.7). In the
      neurogenic bladders determined to be underactive (n=11, including post pelvic
      surgery, post infra-sacral level spinal cord injury and diabetes patients), the
      higher CPT values of bladder mucosal sensory functions were found at 5Hz
      (p<0.05), 250Hz (p=0.07), and 2000Hz (p<0.05) compared to the controls.
      CONCLUSIONS: Quantitative neuroselective measurement of CPT values in the human
      bladder mucosal function was feasible. Hypersensitivity or hyposensitivity of the
      urinary sensory function could be determined using the CPT values in comparison
      to control. The quantitative neuroselective estimation of the bladder sensory
      functions in different types of sensory peripheral nerve fibers may contribute to
      the appropriate selection of therapeutic strategy in patients with urinary
      sensory dysfunction.

PMID- 14667520
TI  - Surgical treatment of Peyronie's disease by the intracavernosal plaque excision
      method: a new surgical technique.
AB  - OBJECTIVE: A new surgical method of treating Peyronie's disease consisting in
      intracavernosal excision of the plaque is presented. MATERIAL AND METHODS: The
      operation was performed on 16 men aged from 34 to 65 years (mean 50.2 years). The
      angle of penile curvature was 30 degrees to 60 degrees. Thirteen (81.25%) had
      impaired intercourse because of penile deformity and in 3 (18.75%) patients it
      was prevented by marked penile curvature. The mean quality of life score (QoL)
      was evaluated as 4.8. The operation consists in incising the corpus cavernosum
      parallel to the plaque and through this incision removing the plaque from the
      inside without incising or replacing the underlaying tunica albuginea. RESULTS:
      Follow-up examinations made after 3, 6 and 12 months revealed normal, painless
      erection in all the patients. In 2 (12.5%) intercourse was impaired only by
      persistent penile curvature of over 20 degrees. Mean QoL score -1.1. CONCLUSIONS:
      In our opinion intracavernosal plaque excision is a simple method, easier to
      perform and less invasive than the operative methods applied to date. It
      eliminates the pain, does not result in a shortening of the penis, loss of
      sensation or erectile dysfunction. It ensures a considerable improvement in the
      QoL of the patients treated.

PMID- 14667521
TI  - Long-term results of a prospective randomized study comparing two different
      antireflux techniques in orthotopic bladder substitution.
AB  - PURPOSE: We compared the long-term functional results following two different
      reflux prevention techniques in orthotopic ileal bladder substitution in a
      prospective controlled randomized study. METHODS: The study included 60 patients
      for whom orthotopic bladder replacement was indicated. The treated patients were
      prospectively randomized into two groups: group I (30 patients) underwent ileal W
      neobladder with serous lined extramural tunnel and group II (30 patients)
      received hemi-Kock pouch with intussuscepted nipple valve. Laboratory evaluation
      included estimation of serum creatinine while radiological studies included IVU
      and voiding studies. Urodynamic evaluation was an integral part of our
      investigation. RESULTS: Patients and tumor characteristics were comparable
      between both groups. No operative or postoperative mortality were observed in
      either. Early complications were encountered in 5 (16.7%) and 4 (13.3%) patients
      in the two treated groups respectively (p=0.72) and most were treated
      conservatively. Twenty patients in group I and 19 in group II were evaluable. The
      mean follow up was 73.9+/-6.6 and 72.9+/-5.6 months in the treated groups
      respectively. Day and night time continence was comparable between both groups.
      Ascending studies demonstrated reflux in 3 (7.7%) of the reimplanted units in
      group I versus 2 (5.3%) in group II (p=0.81); IVU showed uretero-ileal
      anastomotic strictures in 2 renal units with both the serous lined extramural
      tunnel (5.1%) and the ileal nipple valve (5.3%) techniques (p=0.98). One patient
      in group I had pouch stone compared with 5 in group II (p=0.08). Urodynamic
      characteristics were also comparable in both groups. CONCLUSION: The study
      provided evidence that the long-term functional results following serous lined
      extramural tunnel are as equal as the nipple valve. Furthermore, it spares the
      use of extra-bowel length, does not need staples and allows retrograde endoscopic
      procedures.

PMID- 14667522
TI  - Determinants of erectile dysfunction risk in a large series of Italian men
      attending andrology clinics.
AB  - OBJECTIVE: To assess determinants of ED in men who asked for a free of charge
      andrologic consultation during a week focused on andrologic prevention in Italy.
      METHODS: Men were invited to attend 178 participating andrology centers for a
      free of charge visit for counselling about urologic or andrologic conditions.
      Data were recorded with a simple questionnaire used by all centers. RESULTS: 2499
      (19.9%) were diagnosed having ED. The frequency of ED increased with age, ranging
      from 4.6% in men under 25 years, to 37.6% in men over 74. In comparison with men
      with primary education the OR of ED was 0.8 (95% CI 0.7-0.9) in men with
      secondary education and 0.7 (95% CI 0.6-0.9) in those with university degree.
      After adjusting for age, the risk of ED was significantly higher in men consuming
      more than 3 glasses/day of alcoholic drinking (OR 1.4, 95% CI 1.1-2.0), in
      subjects smoking more than 10 cigarettes/day (OR 1.2, CI 95% 1.1-1.4) and in
      former smokers (OR 1.2, CI 95% 1.1-1.4). Men performing at least two hours per
      week of physical activity had a decreased risk of ED (OR 0.8, CI 95% 0.7-0.9). We
      found an increased risk of ED in men with diabetes (OR 1.2, 95% CI 1.1-1.4),
      hypertension (OR 1.3, 95% CI 1.1-1.4), cardiopathy (OR 1.5, 95% CI 1.3-1.8) and
      hypercholesterolemia (OR 1.4, 95% CI 1.2-1.6). CONCLUSIONS: This study provides
      further data on determinants of ED risk in a large data set and underlines the
      relationship between ED and cardiovascular diseases.

PMID- 14667523
TI  - Diagnostic significance of PSA density adjusted by transition zone volume in
      males with PSA levels between 2 and 4ng/ml.
AB  - OBJECTIVE: To investigate the diagnostic significance of prostate-specific
      antigen (PSA), density (PSAD), and PSAD adjusted by transition zone volume
      (PSATZD) in men with PSA levels between 2.1 and 4.0ng/ml. METHODS: Between 1993
      and 2000, 69 men with PSA levels between 2.1 and 4.0ng/ml underwent transrectal
      ultrasonography (TRUS) and 8-core prostate biopsy. Diagnostic accuracies for
      various cut-offs of PSAD and PSATZD were investigated according to subdivided PSA
      levels of 2.1 to 3.0ng/ml and 3.1 to 4.0ng/ml. RESULTS: The detection rate of
      prostate cancer was 21.7% (15/69). The percentage of patients with extracapsular
      disease was 33.3% (5/15) and primary Gleason grade 4 or 5 was obtained in 4
      (26.7%) patients. The transition zone volume and PSATZD in cancer cases were
      significantly different in comparison with those in non-cancer cases. The area
      under the receiver operating characteristic curve for PSATZD was significantly
      higher in comparison with that for PSAD in the same subdivided PSA ranges. The
      diagnostic efficiency for PSATZD was higher than that for PSAD. The diagnostic
      efficiency showed the highest value at the cut-off level for PSATZD of 0.23 and
      0.28 in men with PSA levels of 2.1 to 3.0ng/ml and 3.1 to 4.0ng/ml, respectively.
      CONCLUSIONS: The use of PSATZD cut-offs as a biopsy indication may reduce many
      unnecessary biopsies without missing most prostate cancer cases in the PSA range
      of 2.1 to 4.0ng/ml.

PMID- 14667524
TI  - Intravesical infusion of resiniferatoxin by a temporary in situ drug delivery
      system to treat interstitial cystitis: a pilot study.
AB  - PURPOSE: Interstitial cystitis (IC), a syndrome characterized by motor and
      sensory dysfunction of the lower urinary tract, represents a diagnostic and
      therapeutic challenge even to highly skilled physicians. We investigated the
      technical feasibility and the clinical efficacy of a prolonged intravesical
      instillation of RTX by in situ drug delivery system in patients with IC. MATERIAL
      AND METHODS: 5 female patients (mean age 48.7 years) received a prolonged
      infusion of a saline solution containing 10nM of resiniferatoxin at the flow rate
      25microl/h by the MiniMed 407C Infusion Pump (MiniMed Sylmar, CA, USA), connected
      to sovrapubic 5Fr mono Pigtail catheter, for 10 days. All patients reported
      frequency, nocturia and urgency, and symptoms of pelvic pain for at least six
      months. They showed the absence of urinary tract infection within the last three
      months, the absence of functional disorders of lower urinary tract and no other
      vesical or urethral pathology. The pre-treatment (PT) frequency/volume (FV) chart
      and a pain score (VAS score) were recorded. Patients were evaluated after 30 days
      from the end of infusion (primary end point, PEP) and after three months
      (secondary end point, SEP). RESULTS: At PEP frequency reduced from 11.3+/-1.39 to
      7.4+/-1.51 (p<0.01) and nocturia from 3.6+/-0.54 to 1.2+/-0.44 (p<0.01). A highly
      significant reduction of pain score was observed at PEP: it decreased to 2.4+/
      0.54 from 6.7+/-0.83 (p<0.01). The pain score remained significantly lower at SEP
      (3.2+/-0.44 p<0.05). Nocturia was also statistically reduced at SEP (1.9+/-0.74)
      as well as frequency (8.7+/-1.76). No side effects were reported during the
      infusion as well as after the removal of the catheter. CONCLUSION: The present
      study demonstrates that the prolonged intravesical instillation of a drug by in
      situ drug delivery system is a feasible procedure and seems to support the
      efficacy of RTX in the treatment of IC patients. However further studies are
      necessary and mandatory to confirm our results and to define the exact action
      mechanism of prolonged infusion of RTX, the dosage and the treatment schedule.

PMID- 14667525
TI  - Laparoscopic extraperitoneal adenomectomy (Millin): pilot study on feasibility.
AB  - OBJECTIVE: The aim of the present work is to describe the surgical technique and
      to assess the feasibility of laparoscopic extraperitoneal adenomectomy in a pilot
      study. METHODS: Eighteen consecutive patients in whom an open adenomectomy was
      planned were operated on in a laparoscopic extraperitoneal fashion. In all
      patients indication was based on objective signs of obstruction. The laparoscopic
      approach was standard in all cases as follows: creation of a preperitoneal
      workspace, haemostatic control of lateral venous vesicoprostatic pedicles,
      transversal anterior incision of the prostate capsule, progressive enucleation of
      the adenoma with the help of an harmonic scalpel, suture of the posterior bladder
      neck to the prostate fossa, closure of the prostate capsule, and retrieval of the
      specimen. Feasibility was assessed by objective operative parameters
      (reconversion, operating time, and blood loss and transfusion requirements) and
      per operative complications. Data on short term follow-up are also available.
      RESULTS: Mean age of the patients was 67.8 years (S.D. 6.2) and mean prostatic
      weight calculated by TRUS 95.1cm(3) (S.D. 28.1). Mean maximal flow (Q(max)) was
      4.3ml/s (S.D. 3.4) with four patients (22.2%) presenting in retention. Mean
      duration of intervention was 145min (S.D. 32.5) and mean blood loss 192ml (S.D.
      178). Mean excised tissue was 47.6g (S.D. 30). Neither conversions to open
      prostatectomy nor transfusions were required. The urethral catheter remained in
      place an average of 3.0 days (S.D. 2.4) in 14 patients, while 4 needed a re
      catheterization. Mean postoperative hospital stay was 5.9 days (S.D. 5.5). Five
      patients (27.7%) presented complications during follow-up, mild in most of the
      cases but one who required a secondary intervention for persistent obstruction.
      CONCLUSIONS: Laparoscopic extraperitoneal adenomectomy (Millin's procedure) is
      feasible with a reasonable complication rate. Although comparison with open
      adenomectomy is not yet available, this technique might have potential advantages
      in terms of blood loss and postoperative catheter time.

PMID- 14667526
TI  - Alfuzosin improves penile erection triggered by apomorphine in spontaneous
      hypertensive rats.
AB  - OBJECTIVES: Growing evidence suggest that BPH is a risk factor for ED. Since
      alfuzosin is a cornerstone in the treatment of BPH patients, we assessed the
      effect of alfuzosin on erectile function in rats when combined with a pro
      erectile drug such as apomorphine. METHODS: Potencies of alfuzosin, apomorphine
      or the combination to relax norepinephrine (NE) precontracted corpus cavernosum
      tissue of spontaneous hypertensive rats (SHR) were determined. In anaesthetized
      rats, intracavernous and blood pressures were recorded after administration of
      apomorphine (10-250microg/kg s.c.) and alfuzosin (3-30microg/kg i.v.). RESULTS:
      Alfuzosin fully relaxed the NE-precontracted penile tissue (pIC(50)=6.62+/-0.7)
      while apomorphine, up to 10microM, did not produce any relaxation. The potency of
      alfuzosin to relax erectile tissue was not further enhanced with 10microM
      apomorphine. Apomorphine induced erections in rat while alfuzosin alone did not.
      However, alfuzosin (30microg/kg) significantly enhanced the potency of
      apomorphine, to induce erections (ED(50)=25microg/kg versus 57microg/kg). In
      addition, alfuzosin even at 3microg/kg, significantly increased the
      intracavernous pressure (ICP) during erectile events up to 52-55mmHg when
      compared to ICP values of 29mmHg with 50microg/kg apomorphine alone. CONCLUSION:
      These results show that alfuzosin enhances the number and amplitude of erections
      induced by apomorphine in SHR. Therefore, clinical evaluation of alfuzosin in
      association with apomorphine is warranted.

PMID- 14667527
TI  - A novel technique to eliminate cross-contamination when making wells on slides
      for rabies diagnosis.
AB  - The direct fluorescent antibody (DFA) rabies diagnostic test requires demarcating
      desirable areas of brain tissue slip smear slides to be stained, traditionally
      achieved by applying paint from a tech pen or using a wax pencil to form a circle
      or dam-like ring or well into which rabies conjugate is expelled. Unfortunately,
      using these instruments poses a possibility of cross-contamination by transfer
      via the pen or pencil tip of rabies antigen from one slide to another. A new
      method was developed to avoid cross-contamination. The open end of a disposable
      glass test tube, dipped into a shallow reservoir of nail polish, was used to
      apply a dam-like ring about the slip smear area to be stained, after which the
      test tube was discarded, thereby precluding tissue transfer.

PMID- 14667528
TI  - Real-time quantitative PCR-based serum neutralization test for detection and
      titration of neutralizing antibodies to chicken anemia virus.
AB  - Detection and titration of chicken anemia virus (CAV)-neutralizing antibodies has
      relied on tedious, time-consuming passaging of infected cells, or subjective
      recognition of cytopathic effect in individual cells, because CAV replicates in
      culture only in lymphoblastoid cell lines, and thus generates no plaques. This
      paper describes a rapid method, in which CAV genomes in infected cells are
      quantitated by qPCR 3-4 days postinfection (p.i.), without passaging cells. Three
      sera, weakly positive with a commercial CAV ELISA kit, from broiler chickens
      immunized with a commercial CAV vaccine, were used to develop the assay. Virus
      neutralization titers of these sera were determined using two different CAV
      susceptible cell lines (MDCC-MSB1 and MDCC-CU147) by the conventional method of
      passaging cells infected with 10,000 TCID(50) CAV per well, and by qPCR-based
      methods using cells infected with 100 or 10,000 TCID(50) per well in 24-well or
      96-well plates. The method was also adapted to conventional PCR. The positive
      sera exhibited virus neutralization activity at dilutions ranging from 1:10 to
      1:320 by the various assays. Although virus neutralization titers differed
      somewhat depending on the assay conditions used, the relative order of the titers
      of the three positive sera was the same for all assays. The qPCR-based assays are
      as sensitive and more rapid for detection of neutralizing antibody than the
      conventional assay based on passaging infected cells, and more sensitive for
      detection of low-level CAV antibodies than a commercial blocking ELISA.

PMID- 14667529
TI  - Stable expression of three genes from a tricistronic retroviral vector containing
      a picornavirus and 9-nt cellular internal ribosome entry site elements.
AB  - Retroviral vectors are used widely to deliver heterologous genes into cells. In
      order to express three genes from a single RNA molecule, a retroviral vector that
      contains two divergent internal ribosome entry site (IRES) sequences has been
      constructed successfully. To eliminate the high frequency of recombination within
      a mulicistronic retrovirus vector, a 9-nt segment of a cellular mRNA IRES and a
      picornaviral IRES were used, since these two IRES sequences have minimal sequence
      homology. After a single round of replication, most cells infected with this
      vector stably expressed the three genes while approximately 40% of cells infected
      with another tricistronic retroviral vector that contains two copies of an
      identical IRES sequence lost expression of the gene located between these two
      sequences.

PMID- 14667530
TI  - Validation of a foot-and-mouth disease antibody screening solid-phase competition
      ELISA (SPCE).
AB  - This paper describes the validation of a solid-phase competition enzyme-linked
      immunosorbent assay (SPCE) for the serological detection of antibody to serotype
      O foot-and-mouth disease (FMD) in sheep, cattle and pigs. The specificity of the
      SPCE was calculated from the results of testing known negative sera from sheep,
      cattle and pigs (n=3030, 1418 and 1495, respectively). The mean percentage
      inhibition (PI) for known negative sheep, cattle and pig sera were 19.3, 24.1 and
      20.8%, respectively. The specificity of the SPCE at a cut-off point (COP) of 60
      PI was 99.50% for sheep sera, 99.44% for cattle sera and 100% for pig sera. The
      analytical sensitivity of the SPCE was examined by testing sera from sheep,
      cattle and pigs. Based on the testing of serial bleeds from experimentally
      infected animals, seroconversion at the 60 PI COP occurred between 4 and 9 days
      post-infection or -exposure, similar to that observed using the virus
      neutralisation test (VNT) with a COP of 1/45. When applied to 267 sheep and 143
      pig samples, that were obtained in Great Britain (GB) during the 2001 FMD UK
      outbreak, the SPCE identified more positive samples than did the VNT. Estimates
      of the accuracy, repeatability and reproducibility of the SPCE were verified
      during the large-scale serosurveillance necessitated by the 2001 outbreak.
      Results from field and experimental sera showed that when compared against the
      VNT, the sensitivity of the SPCE was less affected by the choice of virus strain
      used in the test. Using the O(1) UKG 2001 FMD virus in the VNT with samples
      representative of the uninfected GB sheep population, the test specificity was
      100% at a COP of 1/45.

PMID- 14667531
TI  - A simple method for the rapid purification of copia virus-like particles from
      Drosophila Schneider 2 cells.
AB  - Drosophila retrotransposon copia produces virus-like particles (VLPs) in cultured
      Drosophila cells. The VLPs contain copia RNA and reverse transcriptase activity,
      and thus, play a major role in copia replication. Here, we report a rapid and
      simple method for the purification of copia VLPs from Drosophila Schneider 2 (S2)
      cells. The VLP purification procedure consists of a series of short
      centrifugation steps and eliminates the tedious and time-consuming performance of
      sucrose, metrizamide and cesium chloride (CsCl) gradients. The purity and
      presence of VLPs at different purification steps was monitored by transmission
      electron microscopy (TEM), immunochemical detection methods, and by Northern blot
      analysis. In addition to providing a fast protocol for VLP purification, our
      results also show that copia particles are mainly located in the nucleus of S2
      cells. This new protocol may find broad applications for the purification of
      various other VLPs, and thus, may be of great value to other investigators with
      similar interests.

PMID- 14667532
TI  - Sensitive and specific detection of proviral bovine leukemia virus by 5' Taq
      nuclease PCR using a 3' minor groove binder fluorogenic probe.
AB  - Sensitive assays are required to detect proviral bovine leukemia virus (BLV) in
      donor cattle used for the in vivo preparation of Australian tick fever vaccines.
      5' Taq nuclease assays using 3' minor groove binder DNA probes (TaqManMGB) were
      developed and compared to conventional PCR assays for sensitive detection of
      Australian BLV. Seven beef and dairy herds were screened using DNA prepared by a
      variety of protocols to evaluate these tests. Comparative sensitivities of PCR
      tests were determined by testing log(10) dilutions of plasmids with inserted BLV
      sequences. Animals were also screened by the BLV standard agar-gel
      immunodiffusion test (AGID) and commercial enzyme linked immunosorbent assays
      (ELISA) for antibodies, and an ELISA for detecting viral antigens expressed (VAE)
      in lymphocyte cultures. The TaqMan MGB assay based on the pol region was the most
      sensitive and specific for the detection of BLV. This is the first report of a
      sensitive BLV 5' Taq nuclease assay.

PMID- 14667533
TI  - Assessment of different commercial RNA-extraction and RT-PCR kits for detection
      of hepatitis A virus in mussel tissues.
AB  - In the present study, the efficiency of several nucleic acid extraction and RT
      PCR commercial kits for the detection of hepatitis A virus (HAV) from seeded
      mussel tissue samples was evaluated in comparison with the "in-house" method used
      currently in our laboratory. The best results were achieved with Total Quick RNA
      Cells & Tissues version mini (Talent) for RNA extraction and the Superscript One
      Step RT-PCR System (Life Technologies) for the RT-PCR reaction, obtaining a
      detection limit of 0.1-1pfu/mg of mussel tissue. A slightly lower sensitivity (in
      1logunit) was achieved using the Rneasy plant mini kit (Qiagen) and the Total
      Quick RNA Cells & Tissues version maxi in combination with the Superscript RT-PCR
      system. The conventional method usually employed in our laboratory resulted in a
      sensitivity of 300pfu/mg of tissue. Taken together, these findings indicate that
      the combination of Total Quick RNA Cells & Tissues version mini and Superscript
      One-Step RT-PCR System cannot only improve significantly the sensitivity for the
      HAV detection from mussel, but are also labor and time saving and easy to
      standardize.

PMID- 14667534
TI  - Quantitative detection of human immunodeficiency virus type 1 (HIV-1) viral load
      by SYBR green real-time RT-PCR technique in HIV-1 seropositive patients.
AB  - HIV-1 viral load represents a basic marker for evaluation of the rate and
      severity of HIV-1 related disease and to monitor the effectiveness of treatment.
      An SYBR green-based real-time RT-PCR (SYBR green real-time RT-PCR) revealed by
      Light Cycler technology was evaluated for quantitation of HIV-1 RNA viral load in
      plasma of HIV-1 seropositive patients. The performance of the SYBR green real
      time PCR was assessed on 56 HIV-1 seropositive patients under highly active
      retroviral therapy (HAART) and 25 blood donors. The results demonstrated that
      this technique detected 50 HIV-1 RNA copies per millilitre of plasma. Moreover,
      we compared real-time RT-PCR with the b-DNA technique considered widely a
      reference technique for HIV-1 RNA viral load measurement. The parallel
      quantitative analysis of HIV-1 positive samples showed a high correlation
      (r=0.908) between the two methods. Although b-DNA and the real-time-based method
      gave similar sensitivity, the assay determined quantitatively HIV-1 RNA copies in
      4 out of 16 samples shown as undetectable by b-DNA. The SYBR green real-time RT
      PCR represents a good alternative to b-DNA assay in HIV-1 viral load
      determination especially during the monitoring of HAART treatment.

PMID- 14667535
TI  - A simple semi-rapid HIV-1&2 confirmatory immunoassay using magnetic particles.
AB  - The Bionor HIV-1&2 Confirmatory Test is a semi-rapid simple immunoassay based on
      magnetic particles for the confirmation of serological status to human
      immunodeficiency virus (HIV). The specificity and sensitivity of this assay was
      evaluated by comparison with the Diagnostic Biotechnology HIV-1 Western blot (WB)
      2.2 and the HIV-2/SBL-6669 WB. Bionor's confirmatory test demonstrated 98%
      specificity when testing sero-negative blood donors and false positive sera in
      screening tests compared to 81.5 and 71.6%, respectively, using the HIV-1 WB. The
      sensitivity of this assay for HIV-1 antibody positive sera was 97.9% compared to
      the WB which was 99.5%. When testing confirmed HIV-2 antibody positive samples,
      2/100 scored negative using this confirmatory test similar to other HIV-2 peptide
      based line immunoassays available commercially, whilst 8/100 were indeterminate
      reacting to HIV-2 membrane antigens only. Bionor's confirmatory test detected HIV
      1 seropositivity earlier than the WB in longitudinal seroconversion panels and
      could discriminate between HIV-1 and -2 infection. The number of indeterminate
      responses was generally reduced significantly using Bionor's confirmatory test
      compared to the HIV-1 WB. The greater specificity, speed and ease of
      interpretation of Bionor's confirmatory test renders it an attractive and cost
      effective alternative to the WB for confirming HIV serological status worldwide.

PMID- 14667536
TI  - Viral growth assay to evaluate the replicative capacity of HIV-1 isolates.
AB  - The replicative capacity of HIV is studied by carrying out replication
      competition experiments with the insertion of the gene of interest. These assays
      cannot capture the complicated patterns of mutations of different genes.A cross
      sectional study was carried out on 10 HIV-infected nai;ve patients and on 15
      patients failing HAART. The CD8-depleted PBMCs, with known proviral DNA and
      cellular HIV-RNA copy numbers, were cultured. A reference curve was determined
      using the data obtained from 10 nai;ve patients. The replicative capacity was
      calculated as the ratio multiplied by 100 of the p24 antigen level of isolates
      over the p24 antigen level determined on the reference curve.A linear correlation
      between p24 antigen level and the infectious doses of HIV-DNA alone or plus
      cellular RNA copy number of PBMCs was found in naive patients (r=0.63, P<0.001
      and r=0.67, P<0.001, respectively). Although all patients failing therapy had
      strains with impaired replicative capacity, a wide range of values (0.1-74.5%)
      was detected. All strains with a replicative capacity above 10% had non
      nucleoside reverse transcriptase inhibitors related mutations.A viral assay to
      evaluate the HIV replicative capacity is described. The high variability of
      replicative capacity confirms the need to undertake replicative capacity assay
      using the whole virus.

PMID- 14667537
TI  - Performance attributes of the LCx HCV RNA quantitative assay.
AB  - The LCx HCV RNA quantitative assay (Abbott Laboratories, North Chicago, IL) is
      designed to use competitive reverse transcriptase-polymerase chain reaction (RT
      PCR) and microparticle enzyme immunoassay (MEIA), in combination with a modified
      Qiagen sample preparation method, to measure the level of hepatitis C virus (HCV)
      in human plasma and serum. The assay provides quantitative results in
      international units (IU) of HCV RNA/ml, in copies of HCV RNA/ml, or their log
      (base 10) equivalents. A conversion study determined that 1IU equals 4.3 copies.
      The LCx HCV assay detected HCV RNA transcripts representative of genotypes 1-6
      with near equal efficiency. The assay did not cross-react with high
      concentrations of 21 potentially cross-reactive microorganisms or with 100 HCV
      negative specimens. The lower limit of detection was demonstrated to be 23IU/ml.
      The LCx assay had similar sensitivity to the Roche Amplicor HCV (version 2.0)
      qualitative assay when used to test panels containing 6, 12, 23, and 47IU/ml. The
      assay linear range was shown to extend from 23 to 2.3millionIU/ml. The intra
      assay standard deviation (S.D.) was < or =0.066 logIU/ml for the four HCV
      positive samples tested, while for the same samples the observed inter-assay S.D.
      was < or =0.075 logIU/ml. The overall mean assay quantitation value for seven HCV
      positive WHO-standardized Acrometrix NAP linearity panel members was within 0.06
      logIU/ml of the mean assigned value. The assay was demonstrated to correlate
      acceptably against the Roche Amplicor HCV monitor test (version 2.0). These data
      suggest that the assay is standardized appropriately against the WHO standard
      across its linear range and can be used for quantitation of HCV. In addition,
      with a sensitivity of 23IU/ml, the assay can be used to determine if post-therapy
      viral clearance has occurred.

PMID- 14667538
TI  - Quantitation of hepatitis B surface antigen by an automated chemiluminescent
      microparticle immunoassay.
AB  - A fully automated chemiluminescent microparticle immunoassay (Architect HBsAg QT)
      was used for the detection and quantitation of hepatitis B surface antigen
      (HBsAg). The assay is capable of processing up to 800 HBsAg tests per hour. The
      concentration of HBsAg is determined by utilizing a previously generated
      Architect HBsAg calibration curve. Architect HBsAg QT sensitivity was found to be
      around 0.2ng/ml which is equivalent or superior to other known and commercially
      available enzyme immunoassays and/or chemiluminescent immunoassays. We performed
      a quantitative study of HBsAg, HBeAg, HBV-DNA and HBV-DNA polymerase in over 733
      sera obtained from 43 chronic hepatitis B carriers. Serum HBsAg levels detected
      by Architect HBsAg QT were found to be higher in HBeAg-positive than in anti-HBe
      positive HBV chronic carriers and correlated with the level of serum HBV-DNA and
      HBV-DNA polymerase.

PMID- 14667540
TI  - Convolution of mini distributions for fitting evoked synaptic amplitude
      histograms.
AB  - According to a basic formulation of the quantal model, evoked synaptic currents
      are made up of a linear summation of uniquantal synaptic currents, which in turn
      are equivalent to the spontaneous miniature synaptic currents ('minis') that
      often persist when evoked neurotransmitter release is blocked. Here I describe a
      convolution method for calculating linear summations of the 'mini' amplitude
      distribution, which can then be fitted to the measured amplitude distribution for
      evoked synaptic currents. Provided certain conditions are satisfied, this method
      can give information about the statistics of neurotransmitter release even when
      clear quantal peaks are not apparent in the evoked amplitude distribution. The
      method is illustrated by an experiment in which the appropriate minis are
      identified with the asynchronous excitatory postsynaptic currents that follow
      synaptic stimulation when the cell is bathed in strontium. Finally, I discuss the
      assumptions behind the convolution method, and the conditions under which the
      properties of the minis are likely to be appropriate for an analysis of this
      type.

PMID- 14667541
TI  - Variance-mean analysis: a simple and reliable approach for investigating synaptic
      transmission and modulation.
AB  - The mechanisms underlying synaptic plasticity can be investigated by analyzing
      synaptic amplitude fluctuations before and after a synaptic modulation. However,
      many older fluctuation analysis techniques rely on models of synaptic
      transmission that incorporate unrealistic simplifying assumptions or have too
      many free parameters. As a result, these techniques have sometimes produced
      counterintuitive or contradictory results. In contrast, the variance-mean (V-M)
      technique requires fewer assumptions and is more robust than previous approaches.
      It achieves these improvements by focusing on two key parameters of synaptic
      transmission, the average probability that a vesicle is released from a synaptic
      terminal following a presynaptic stimulus (Pav), and the average amplitude of the
      postsynaptic response to a vesicle of transmitter (Qav). To apply V-M analysis, a
      fluctuating postsynaptic current (PSC) is recorded at several different
      extracellular Ca2+ or Cd2+ concentrations. The variance of the PSC amplitude is
      plotted against the mean amplitude at each concentration, forming a parabola. The
      degree of parabolic curvature estimates Pav, and the limiting slope under low
      release conditions estimates Qav. The shape of the V-M parabola changes in
      characteristic ways following each of the three standard forms of synaptic
      modulation: a change in Qav (postsynaptic), a change in Pav (presynaptic), or a
      change in the number of terminals (N). The approach does not require specialized
      software, and can even be implemented as a purely graphical technique. V-M
      analysis has been used to investigate the site of expression of long-term
      potentiation and the mechanisms underlying paired-pulse depression. This report
      presents a detailed mathematical development of the technique, and explores the
      limiting conditions under which it can confidently be applied. V-M analysis
      requires fewer than 100 PSC amplitude measurements to accurately estimate Pav and
      Qav, and it can reliably identify whether a synaptic modulation occurs at a pre-
      or postsynaptic site. In contrast to other techniques, V-M analysis is largely
      insensitive to recording noise, nonuniform modulation and intrinsic variability
      of the unitary synaptic amplitude.

PMID- 14667542
TI  - Estimation of nonuniform quantal parameters with multiple-probability fluctuation
      analysis: theory, application and limitations.
AB  - Synapses are a key determinant of information processing in the central nervous
      system. Investigation of the mechanisms underlying synaptic transmission at
      central synapses is complicated by the inaccessibility of synaptic contacts and
      the fact that their temporal dynamics are governed by multiple parameters.
      Multiple-probability fluctuation analysis (MPFA) is a recently developed method
      for estimating quantal parameters from the variance and mean amplitude of evoked
      steady-state synaptic responses recorded under a range of release probability
      conditions. This article describes the theoretical basis and the underlying
      assumptions of MPFA, illustrating how a simplified multinomial model can be used
      to estimate mean quantal parameters at synapses where quantal size and release
      probability are nonuniform. Interpretations of the quantal parameter estimates
      are discussed in relation to uniquantal and multiquantal models of transmission.
      Practical aspects of this method are illustrated including a new method for
      estimating quantal size and variability, approaches for optimising data
      collection, error analysis and a method for identifying multivesicular release.
      The advantages and limitations of investigating synaptic function with MPFA are
      explored and contrasted with those for traditional quantal analysis and more
      recent optical quantal analysis methods.

PMID- 14667544
TI  - Quantal analysis based on density estimation.
AB  - When direct measurements of the quantal parameters for a synapse cannot be made,
      these parameters can be extracted from an analysis of the fluctuations in the
      evoked response at that synapse. In this article, a decision tree is described in
      which the ability of the data to match simple models of quantal transmission is
      rigorously compared with its ability to fit progressively more complex models.
      The Wilks statistic is the basis for this comparison. The procedure commences
      with optimal transformation of peak amplitude measurements into a probability
      density function (PDF). It then examines this PDF against various models of
      transmission, commencing with a multi-modal but non-quantal distribution, then to
      a multi-modal distribution with quantal peak separation with and without quantal
      variability, and, finally, the constraints of uniform and non-uniform release
      probabilities are imposed. These procedures are illustrated by example. A
      comparison is made between the relative sensitivities of the Wilks statistic and
      the chi2 goodness-of-fit criteria in rejecting inappropriate models at all stages
      in these procedures.

PMID- 14667543
TI  - Combining deconvolution and fluctuation analysis to determine quantal parameters
      and release rates.
AB  - Analysis methods are described which integrate information from fluctuation
      analysis with that from deconvolution. Together the two approaches allow to
      derive a consistent quantitative description of quantal release (both evoked,
      spontaneous and asynchronous) under conditions in which quantal parameters may
      change during a repetitively applied stimulation protocol. Specifically, our
      methods take into account the effects of accumulating transmitter in the synaptic
      cleft and postsynaptic receptor desensitization, which may develop during strong
      stimulation. Several ways to handle non-stationarities are described. Examples
      are provided for the Calyx of Held, a glutamatergic synapse, in which both the
      pre- and the postsynaptic compartments can be voltage-clamped.

PMID- 14667545
TI  - Combining principal component and spectral analyses with the method of moments in
      studies of quantal transmission.
AB  - This chapter considers methods for measurements of postsynaptic responses and
      simple approaches to the estimation of parameters of quantal release in synapses
      of the central nervous system of vertebrates. The use of these methods is
      illustrated by the analysis of single-fibre and "minimal" monosynaptic
      postsynaptic potentials (PSPs) or currents (PSCs) recorded from neurons of the
      frog spinal cord and rat hippocampus. First, we briefly discuss traditional
      methods of the response measurements using peak amplitudes or areas, further
      focusing on a novel method based on multivariate statistical techniques of the
      principal component analysis (PCA). This approach provides typically better
      signal-to-noise ratios and is able to separate two or more response components,
      which can arise due to activation of more than one presynaptic fibre, axon
      collaterals, receptor subtypes or spatially separated transmission sites. Second,
      spectral analysis is introduced as the method of choice to verify whether the
      amplitude fluctuations of the postsynaptic responses have a quantal nature and to
      obtain estimations of the "basic" quantal parameters, i.e. the quantal size (Q)
      and mean quantal content (m), without introducing assumptions on release
      statistics. Third, we show how the method of moments could be applied in the
      framework of the Poisson and binomial models to estimate the basic quantal
      parameters and parameters p and n, which reflect the release probability and
      maximum number of quanta released (or the number of effective release sites),
      respectively. Fourth, we show that the analysis of the moments can also be
      instrumental to reveal non-uniformity of release probabilities and compare how
      several competing models of neurotransmitter release fit to multiple experimental
      data sets.

PMID- 14667546
TI  - Anti-TNF alpha therapy in spondyloarthropathy: deciding who to treat.

PMID- 14667547
TI  - Arthroscopy for knee osteoarthritis.

PMID- 14667548
TI  - What keeps serum calcium levels stable?
AB  - Many body functions require that serum calcium levels remain stable over time.
      This stability is provided by cooperation among three organs: two effectors, the
      bone and the kidney, which control calcium movements into and out of the
      extracellular compartment, and the parathyroid glands, which produce and release
      parathyroid hormone (PTH). PTH acts on the bone and renal tubule. Provided the
      amount released is appropriate, this keeps extracellular calcium levels stable.

PMID- 14667549
TI  - Occupational bone diseases.
AB  - Occupational bone diseases are uncommon, with fewer than 400 cases recognized in
      France since 1990, although many cases have escaped diagnosis. The symptoms lack
      specificity, raising diagnostic challenges. Greater awareness of these conditions
      and of their pathophysiological mechanisms would provide much needed improvement
      in diagnosis and prevention.

PMID- 14667550
TI  - Shoulder surgery: from cuff repair to joint replacement. An update.
AB  - REPAIRING FULL THICKNESS CUFF TEARS.--Despite the sound rationale for repairing
      full-thickness rotator cuff tears, the procedure may fail to restore cuff
      integrity, which is indispensable to optimal cuff function. The functional role
      of each cuff muscle and the factors associated with anatomic failure
      (particularly those related to the muscles and tendons) provide a basis for
      rational patient selection and for determination of the best surgical strategy on
      a case-by-case basis. SHOULDER ARTHROPLASTY IN PATIENTS WITH GLENOHUMERAL JOINT
      DISEASE.--Total shoulder arthroplasty in patients with glenohumeral joint disease
      provides better outcomes than humeral hemiarthroplasty. The choice between a semi
      constrained total prosthesis and a reverse constrained total prosthesis should be
      based on the nature of the joint disease (either centered humeral head or normal
      cuff function or migrated humeral head and abnormal cuff function). At present,
      only the semi-constrained total prosthesis has been proved effective in the long
      term when used in a patient with a centered humeral head and active cuff. This
      provides additional support for repairing cuff tears whenever possible in
      patients who are still young.

PMID- 14667551
TI  - Evaluating inflammatory joint disease: how and when can autoantibodies help?
AB  - The diagnosis of inflammatory joint disease rests on a constellation of symptoms,
      signs, laboratory test results and, occasionally, histological findings.
      Classification criteria have been developed by national learned societies,
      international panels of experts or, more rarely, an expert working alone. These
      criteria are intended to provide a common language for therapeutic trials and
      international publications. Yet, they are often inappropriately used as
      diagnostic tools for the individual patient. Identification of an early
      seroimmunologic marker with high sensitivity and specificity for classifying
      patients with recent-onset joint disease is a daunting challenge. Test
      performance characteristics such as sensitivity, specificity, positive and
      negative predictive values, and the positive or negative likelihood ratio help to
      assess the diagnostic usefulness of a laboratory test in a specific situation.
      The difference between the pretest and posttest likelihoods of obtaining a
      positive or negative result measures the usefulness, or performance, of a
      laboratory test in a specific situation according to the prevalence of the
      disease. A higher positive likelihood ratio indicates a more useful test. In a
      patient with inflammatory joint disease, the diagnosis can be sought by assaying
      a limited number of autoantibodies according to a decision tree. Thus, IgM
      rheumatoid factors (latex test or ELISA) and antibodies to filaggrin or other
      citrullinated proteins (antikeratin antibodies by indirect immunofluorescent
      assay or anticyclic citrullinated peptides by ELISA) identify more than 70% of
      cases of early rheumatoid arthritis with greater than 98% specificity. If these
      markers are negative, testing for antinuclear antibodies by indirect
      immunofluorescent assay on HEp-2 cells identifies 99% of cases of lupus and
      progressive systemic sclerosis. Confirmation of the diagnosis can be obtained by
      characterizing the autoantibodies: thus, presence of antidouble-stranded DNA
      (dsDNA, by the Farr radioimmunoassay, indirect immunofluorescent assay on
      Crithidia luciliae, or ELISA (IgG)) or of antinucleosome antibodies (ELISA)
      indicates lupus, whereas anticentromere, antitopoisomerase I (Scl 70), and
      antinucleolar antibodies point to progressive systemic sclerosis. A positive test
      for antibodies to soluble nuclear antigens of the U1 RNP type suggests mixed
      connective tissue disease or lupus but may indicate scleroderma. Anti-Sm
      antibodies are found in fewer than 10% of lupus patients but are highly specific.
      Anti-SSA (Ro) and anti-SSB (La) suggest lupus or primary Sjogren's syndrome. When
      tests are negative for ANA, several antibodies to cytoplasmic organelles are
      valuable diagnostic tools, such as anti-J01 for polymyositis syndromes and
      antiribosome antibodies for lupus, although their sensitivity is modest (20-25%).
      Finally antineutrophil cytoplasmic antibodies (ANCAs) ensure the diagnosis of
      small-vessel vasculitides, which often involve the lungs and kidneys. Thus, in
      diffuse Wegener's granulomatosis, ANCAs exhibiting the classic cytoplasmic
      pattern and corresponding by ELISA to anti-PR3 are found. In microscopic
      polyangiitis the ANCAs are peripheral and correspond by ELISA to
      antimyeloperoxidase antibodies. Tests for other antibodies are less often needed
      to evaluate inflammatory joint disease.

PMID- 14667552
TI  - Nonpharmacological prevention of osteoporotic fractures.
AB  - In postmenopausal women, the nonpharmacological prevention of osteoporotic
      fractures pursues the dual objective of minimizing bone loss and preventing
      falls. In women with a low fracture risk, optimizing the dietary intake of
      calcium is the main nutritional goal. Regular sustained physical activity should
      be encouraged. In older women, the high risk of proximal femoral fractures
      warrants a number of preventive measures, including calcium and vitamin D
      supplementation, correction of protein deficiency if needed, and minimization of
      the risk of falls. Hip protectors may be useful in institutionalized women at
      high risk for falls. These nonpharmacological measures should be part of a
      comprehensive customized management program used to complement standard
      pharmacological therapy.

PMID- 14667553
TI  - Genetics and clinical practice in rheumatology.
AB  - The dramatic advances made recently in human genome research are fueling
      considerable interest in genetic testing. A specific feature of genetic testing
      is that the results are final and impact not only the patient, but also the
      entire family. Those elements should be factored into the risk/benefit ratio
      evaluation. In France, legislation the differentiates diagnostic tests in
      symptomatic patients from predictive tests in asymptomatic patients with affected
      family members. Only multidisciplinary groups with both clinical and genetic
      expertise can order predictive tests. In all cases the physician must sign a
      statement that informed consent was obtained from the patient prior to testing.
      The test must be done in an accredited laboratory and the result communicated by
      the physician to the patient. Patient confidentiality must be respected,
      particularly regarding family members. In monogenic diseases, the diagnostic
      weight of genetic testing is often considerable, although the limitations should
      be borne in mind. In multifactorial diseases, genetic testing seeks to identify
      risk factors that are usually associated with a low level of risk. The result
      should be interpreted in the light of the clinical presentation, family history,
      and genetic background. The predictive value is closely dependent on the clinical
      presentation but is generally limited, most notably when family members are
      affected. Great care should be taken to avoid causing undue anxiety among
      individuals with positive test results. Diseases that illustrate these aspects
      include Paget's disease of bone, of which inherited variants caused by a mutation
      in a single gene on chromosome 5 have been identified recently, and rheumatoid
      arthritis, which is a multifactorial disease.

PMID- 14667554
TI  - Efficacy data on teriparatide (parathyroid hormone) in patients with
      postmenopausal osteoporosis.
AB  - Until recently, the only therapeutic agents available for postmenopausal
      osteoporosis acted by inhibiting bone resorption and decreased the fracture risk
      by no more than 50%. Teriparatide, the recombinant 1-34 fragment of human
      parathyroid hormone, is a bone formation enhancer that has recently been licensed
      for use in established postmenopausal osteoporosis. Intermittent parathyroid
      hormone administration preferentially stimulates bone formation. The resultant
      increase in bone mass and improvement in bone architecture translate into a large
      decrease in the fracture risk that constitutes a major advance in the treatment
      of postmenopausal osteoporosis. Further work is needed to define the role for
      teriparatide in the therapeutic strategy for postmenopausal osteoporosis and to
      determine whether this agent is best used alone or in synchronous or sequential
      combination with bone resorption inhibitors.

PMID- 14667555
TI  - Vectors for gene therapy of joint disorders.

PMID- 14667556
TI  - Development of new molecules, vectors and cells for therapy of arthritis.

PMID- 14667557
TI  - Modulation of pathways regulating both the invasiveness and apoptosis in
      rheumatoid arthritis synovial fibroblasts.

PMID- 14667558
TI  - Gene therapy in cartilage using electroporation.

PMID- 14667559
TI  - Mesenchymal stem cells and rheumatoid arthritis.

PMID- 14667560
TI  - Risks and benefits of articular gene therapy.

PMID- 14667561
TI  - Contribution of routine joint aspiration to the diagnosis of infection before hip
      revision surgery.
AB  - OBJECTIVES: To define the sensitivity and specificity of routine preoperative hip
      aspiration for diagnosing hip prosthesis infection (HPI) and to separately
      analyze subgroups with and without a clinical suspicion of HPI before aspiration.
      METHODS: From June 1994 to June 1997, all patients scheduled for hip revision
      surgery underwent aspiration of the hip under image intensifier guidance.
      Microbiological results were compared between these preoperative specimens and
      the intraoperative specimens. The reason for surgery was either a clinical
      suspicion of HPI or pain suggesting loosening. RESULTS: The study patients had
      had multiple surgical procedures. HPI was suspected clinically in 39.4% of cases.
      Of the 109 patients who underwent aspiration, 54 had true-negative results, nine
      had false-negative results, and 44 had true-positive results (there were no false
      positive results), yielding a sensitivity of 83% and a specificity of 100%.
      Diagnostic efficiency was 91.6%, positive predictive value was 100%, and negative
      predictive value was 85.7%. In the subset of 43 patients with a clinical
      suspicion of HPI, aspiration identified all the causative organisms in 60.5% of
      cases. Of the 66 patients with no clinical suspicion of HPI, 12 had HPI, and
      aspiration provided the diagnosis preoperatively in seven of these patients,
      radically changing their management plans. Restricting routine aspiration to
      patients whose prosthesis had been implanted within the last 5 years or whose
      erythrocyte sedimentation rate (ESR) was above 30 mm/h would not have modified
      our findings. CONCLUSIONS: Hip aspiration before revision surgery for pain is
      effective in detecting HPI, which can simulate aseptic loosening. However, this
      investigation may be noncontributive in patients who have had their prosthesis
      for more than 5 years and whose ESR is less than 30 mm/h.

PMID- 14667562
TI  - Smoking, gender and rheumatoid arthritis-epidemiological clues to etiology.
      Results from the behavioral risk factor surveillance system.
AB  - OBJECTIVES: This study was undertaken to confirm and extend our earlier
      observation that gender is a biological effect modifier of smoking-rheumatoid
      arthritis (RA) relationship in a diverse national survey sample in the United
      States. METHODS: Smoking history of 644 cases of RA and 1509 geographically
      matched general population controls were compared using weighted logistic
      regression. RESULTS: There were 644 respondents with RA (cases) and 1509
      geographically matched controls. Cases were significantly younger, less educated,
      more likely to be single and female than controls. Among cases 57% were smokers
      while among controls 49% smoked. Among women, after adjusting for age,
      hysterectomy had an age adjusted odds ratio 1.45, (95% CI 0.99-2.10) and
      menopause an adjusted odds ratio 1.18 (95% CI 0.99-2.10) were associated with
      smoking. In univariable analysis ever-smoking was associated with increased risk
      of RA (odds ratio 1.34, 95% CI 1.0-1.81). Among the strata of smokers, there was
      an increasing gradient of risk with increasing exposure to smoking (P = 0.041).
      In separate multivariable models, smoking increased the risk in men (odds ratio
      2.29, 95% CI 1.35-3.90) while in women the risk was not elevated (odds ratio
      0.98, 95% CI 0.67-1.42). After adjusting for the statistically significant
      interaction both female gender (odds ratio 2.30, 95% CI 1.39-3.83) and having
      ever smoked (odds ratio 2.31, 95% CI 1.36-3.94) emerged as significant risk
      factors for RA. CONCLUSIONS: Gender interacts with smoking in by an unknown
      mechanism to lead to differential risk of RA.

PMID- 14667563
TI  - Magnetic resonance imaging in reflex sympathetic dystrophy syndrome of the foot.
AB  - OBJECTIVE: The purpose was to analyze magnetic resonance imaging (MRI)
      abnormalities in reflex sympathetic dystrophy syndrome (RSDS) of the foot, with
      the goal of helping to meet the difficult diagnostic challenges raised by this
      condition. METHODS: Retrospective study of 20 patients with RSDS of the foot, 15
      at the warm phase and five at the dystrophic phase. RESULTS: Of the 15 patients
      at the warm phase, seven had evidence of bone edema (low signal on T1-weighted
      images and high signal on T2, T2 STIR, and fat saturation images) and five had
      occult fractures (linear band of low signal on T1 and T2 weighted images with no
      enhancement after contrast injection). Other abnormalities included soft tissue
      changes in three patients, joint effusion in five, and synovial hypertrophy in
      one. Of the five patients at the dystrophic phase, one had a fracture with a
      joint effusion, one had isolated joint edema, and three had normal MRI findings.
      CONCLUSION: Bone marrow edema is inconsistent at the warm phase of RSDS and is
      never present at the dystrophic phase. Thus, absence of bone edema does not rule
      out RSDS. Fractures may be visible by MRI in one-third of patients with RSDS and
      no clinical or plain radiography evidence of fracturing.

PMID- 14667564
TI  - Evaluating changes in health status: sensitivity to change of the modified Arabic
      Health Assessment Questionnaire in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To test the correlation between clinical improvements in patients with
      rheumatoid arthritis (RA) as defined by the American College of Rheumatology
      (ACR) response criteria and functional improvements as assessed by functional
      measures in the modified Arabic version of the Health Assessment Questionnaire
      (Arabic-HAQ) and to estimate the sensitivity to change of the Arabic-HAQ, in a
      prospective study. METHODS: Eighty-two patients with active RA were given
      methotrexate and followed up prospectively for 12 months. ACR response rates and
      score improvements on the modified Arabic-HAQ were compared. RESULTS: The Arabic
      HAQ scores showed significant sensitivity to change after 6 and 12 months and
      were significantly correlated with the ACR response. Percentages of agreement
      with ACR response levels were high after 6 months and higher still after 12
      months. Standardized effect sizes were 2.34 and 2.84 after 6 and 12 months,
      respectively. Relative efficiency of the total Arabic-HAQ score in relation to
      the tender joint count was greater than 1. CONCLUSION: The Arabic-HAQ is valid
      and sensitive to functional status changes in patients with RA. The results are
      comparable to those of the original HAQ. Thus, the Arabic-HAQ can be used to
      evaluate treatments and to identify changes that are important to RA patients.

PMID- 14667565
TI  - Assessment of the test-retest reliability and construct validity of a modified
      Lequesne index in knee osteoarthritis.
AB  - OBJECTIVES: To assess the test-retest reliability and the construct validity of a
      modified version of the Lequesne index. METHODS: Patients with symptomatic knee
      osteoarthritis (OA) fulfilling the revised criteria of the American College of
      Rheumatology completed the Lequesne index twice at a 3-h interval. Impairment
      outcome measures and patients' perceived discomfort in walking and handicap were
      recorded. An item-by-item analysis was performed. Items having insufficient
      psychometric properties were excluded. Test-retest reliability was assessed using
      the intra-class correlation coefficient (ICC) and the Bland and Altman method.
      Construct validity was investigated using Spearman rank correlation coefficient
      and a factor analysis was performed. RESULTS: Eighty-eight patients were
      included. One question assessing pain (question IE) had a weak reliability (Kappa
      (kappa) = 0.39) and was excluded. The test-retest reliability of the modified
      questionnaire was excellent (ICC = 0.95). Expected convergent and divergent
      correlations were achieved except for visual analog scale pain (VAS P) and VAS
      handicap (VAS H) (0.46 and 0.40, respectively), and the "a priori" double
      stratification was confirmed by factor analysis, explaining 48.7% of the
      variance. CONCLUSION: The modified form of the Lequesne index has sufficient
      psychometric properties to be used to assess pain and function in knee OA in a
      French population.

PMID- 14667566
TI  - Hemarthrosis in acquired hemophilia. Two case-reports.
AB  - The many causes of hemarthrosis include acquired hemophilia due to production of
      autoantibodies to factor VIII. We report two very different cases. CASE 1: This
      woman experienced onset of juvenile idiopathic arthritis at 8 years of age. Her
      first child was born when she was 28-years-old. Three months after delivery,
      vaginal bleeding and recurrent hemarthrosis led to a diagnosis of acquired
      hemophilia (isolated APTT prolongation, 1% VIIIc activity, and 58 U of anti
      factor VIII antibody). Treatment included glucocorticoid therapy, prothrombin
      complex, and intravenous immunoglobulins. She achieved a full recovery within a
      year. CASE 2: In this 84-year-old woman, spontaneous recurrent hemarthrosis with
      hematomas revealed idiopathic acquired hemophilia. Treatment included prothrombin
      complex, factor VIII concentrates, and intravenous immunoglobulins, followed by
      cyclophosphamide and glucocorticoid therapy. Recovery was complete within a year.
      The diagnosis, etiology, prognosis, and treatment of acquired hemophilia are
      discussed. CONCLUSION: Although rare, acquired hemophilia should be considered
      among the causes of hemarthrosis, particularly as a favorable outcome can be
      expected with early diagnosis and appropriate treatment.

PMID- 14667567
TI  - Unusually prolonged course of tuberculous dactylitis with osteitis.
AB  - We report a case of tuberculous dactylitis that was unusual in two regards: the
      bone was infected, and the course was prolonged and atypical, with a spontaneous
      clinical remission followed by a recurrence that led to the diagnosis.

PMID- 14667568
TI  - Intramedullary cavernous angioma. Two case-reports.
AB  - Intramedullary cavernous angiomas are extremely rare. We retrospectively reviewed
      two cases in a 24-year-old man and 40-year-old woman. T2-weighted magnetic
      resonance images showed the cavernoma at the cervical and lower thoracic spine,
      respectively. The patient with cervical involvement also had an asymptomatic
      cavernoma in the cerebellum. In both patients, the outcome was favorable after
      complete surgical removal of the lesion.

PMID- 14667569
TI  - Magnetic resonance imagery and degenerative disease: an experiment from Britanny
      with 105 patients.

PMID- 14667570
TI  - Hyperphosphatemia in multiple myeloma.

PMID- 14667571
TI  - Identification of two proopiomelanocortin genes in zebrafish (Danio rerio).
AB  - Characterization of a newly cloned proopiomelanocortin (POMC) gene in the teleost
      zebrafish, Danio rerio, is reported. This gene is formed by three exons and two
      introns, and its complete cDNA codes for a polypeptide of 222 amino acids.
      Zebrafish proopiomelanocortin (zfPOMC) contains the consensus sequences for ACTH,
      gamma-LPH, beta-MSH and beta-endorphin (beta-END). RT-PCR expression studies
      indicate that zfPOMC is selectively expressed in nervous tissue and in the
      pituitary gland. An homologous sequence to zfPOMC in the zebrafish genome is also
      presented. It is possible that this sequence represents part of a duplicate POMC,
      which might have appeared as a result of an extra genome duplication that have
      taken place in the cyprinidae family or even in all teleosts. Comparisons between
      the two zebrafish beta-endorphins and among these peptides and its homologues in
      other species are also presented.

PMID- 14667572
TI  - Striatal neurons but not nigral dopaminergic neurons in neonatal primary cell
      culture express endogenous functional N-methyl-D-aspartate receptors.
AB  - Developmental expression of N-methyl-D-aspartate (NMDA) receptor subunits were
      determined and compared in striatal and nigral neurons in neonatal primary cell
      cultures. In striatal neurons, NR1, NR2A and NR2B mRNAs and immunoreactivity, and
      NR2D mRNA were found and the maximal levels of NR1 mRNA and immunoreactivity
      expression were found at 6 day-in-vitro (DIV). NMDA receptors found at this stage
      in striatal neurons are likely to contain NR1 plus NR2A, NR2B and NR2D subunits.
      In nigral neurons, NR1 and NR2B mRNAs and immunoreactivity, and NR2D mRNA were
      found and the maximal level of NR1 immunoreactivity expression was found at 10
      DIV. Unlike striatal neurons, NMDA receptors found in nigral neurons are likely
      to contain NR1 plus NR2B and NR2D subunits only. NMDA-induced toxicity assays
      showed that striatal neurons were most susceptible to cell death at around 10 DIV
      but nigral neurons were not susceptible to NMDA-induced cell death at all stages.
      In addition, patch clamp analysis revealed that functional NMDA receptors could
      only be found in striatal neurons but not in nigral dopaminergic neurons in
      vitro. The present results indicate that striatal and nigral neurons are
      programmed to express distinct NMDA receptor subunits during their endogenous
      development in cell cultures. Despite dopaminergic neurons in culture display
      NMDA receptor subunits, functional NMDA receptors are not assembled. The present
      findings have demonstrated that dopaminergic neurons in vitro may behave very
      differently to their counterparts in vivo in terms of NMDA receptor-mediated
      responses. Our results also have implications in transplantations using
      dopaminergic neurons in vitro in treatments of Parkinson's disease.

PMID- 14667573
TI  - Cloning of a novel orphan G protein-coupled receptor (GPCR-2037): in situ
      hybridization reveals high mRNA expression in rat brain restricted to neurons of
      the habenular complex.
AB  - The family of G protein-coupled receptors (GPCRs) is one of the largest protein
      families in the mammalian genome. Receptors belonging to this class mediate the
      effects of very diverse ligands and are responsible for signaling events by
      affecting the activities of enzymes and ion channels. Here we describe the
      cloning and identification of GPCR-2037, a novel and previously not identified
      member of the large family of GPCRs. This orphan GPCR displays several typical
      features of family A type of GPCRs and shows highest homology with the galanin
      receptors 2 and 3. In rat brain, in situ hybridization showed that expression of
      GPCR-2037 mRNA was exclusively localized to neurons of the habenular complex. The
      expression was particularly prominent in the medial habenular nucleus, whereas
      the lateral habenular nucleus exhibited a lower number of labeled cells. The
      restricted and unique expression pattern of GPCR-2037 in the rat brain suggests a
      role for this orphan GPCR in the habenular complex, a brain structure implicated
      in the modulation of various physiological functions. Further studies involving
      the identification of the GPCR ligand will enable the functional characterization
      of this orphan receptor and its role in regulating the habenular complex.

PMID- 14667574
TI  - Rat retinal ganglion cells upregulate the pro-apoptotic BH3-only protein Bim
      after optic nerve transection.
AB  - Increased expression of Bim, a pro-apoptotic member of the Bcl-2 family, has been
      shown to be critical for neuronal apoptosis. To study the involvement of Bim in
      injury-induced cell death in retina, Bim expression was studied in normal rat
      retina and in retina after optic nerve transection using quantitative RT-PCR and
      immunohistochemistry. As a complement to this, the apoptotic regulators Bax, Bcl
      2, caspase-3 and phosphorylated c-jun were studied. The relative levels of Bim
      mRNA in retina were significantly higher 4 days after optic nerve transection and
      below normal levels at 14 days after transection. A parallel increase in the
      number of Bim-immunoreactive cells in the retinal ganglion cell layer could be
      seen. Bim-immunoreactivity localized to retrogradely True Blue-labeled retinal
      ganglion cells. The relative mRNA levels for both Bax and Bcl-2 were higher at 4
      days after transection when compared to normal. Immunoreactivity for Bax, Bcl-2
      as well as for caspase-3 and phosphorylated c-jun, indicative of cell death,
      localized to True Blue-identified retinal ganglion cells 4 days after injury. Bcl
      2 immunoreactivity was also seen on other cells, most likely Muller glia cells.
      In addition, optic nerve transection caused an increase in Bim, Bax, and Bcl-2
      mRNA levels in optic nerve and superior colliculus. Our results suggest that Bim
      is involved in injury-induced retinal ganglion cell death and indicate that the
      increase in Bim and Bax expression promote cell death of axotomized retinal
      ganglion cells whereas the elevation in Bcl-2 in retina may contribute to the
      control of the extent of apoptosis after the optic nerve transection.

PMID- 14667575
TI  - ATF3 enhances c-Jun-mediated neurite sprouting.
AB  - The AP-1 transcription factor c-Jun is induced in axotomized neurons of the
      peripheral and central nervous systems, and in both cases upregulation of c-Jun
      expression has been correlated with axonal regeneration. More recently there has
      been interest in the c-Jun-related bZIP transcription factor, ATF3, and its
      function in neurons. ATF3 is also induced in nerve cells in response to axotomy
      and there is a correlation between increased ATF3 expression and upregulation of
      c-Jun in surviving neurons. Moreover, c-Jun is able to induce expression of ATF3.
      We investigated the effect of co-expressing c-Jun and ATF3 in two neuronal-like
      cell lines to model transcriptional events occurring in axotomized neurons
      undergoing regeneration. We show that expression of ATF3 with c-Jun significantly
      enhances c-Jun-mediated neurite sprouting, and that this phenotype is most likely
      mediated by a physical association of these two transcription factors. Our
      results suggest that a program of axonal regeneration is initiated when both c
      Jun and ATF3 are upregulated in neurons in response to axotomy.

PMID- 14667576
TI  - Day-night variations in zinc sensitivity of GABAA receptor-channels in rat
      suprachiasmatic nucleus.
AB  - In the suprachiasmatic nucleus (SCN), electrical activity, secretion, and other
      cellular functions undergo profound rhythm during day-night cycle due to
      oscillatory expression of clock gene constituents. Although SCN is enriched with
      gamma-aminobutyric acid (GABA)-ergic neurons, it is unknown whether there are
      circadian changes in the GABAA receptor expression and/or function. Here we
      investigated the possible daily variations in zinc sensitivity of GABAA channels
      in rat SCN neurons maintained in brain slices. Extracellular zinc inhibited GABA
      induced currents in all ventrolateral (VL) and dorsomedial (DM) SCN neurons
      studied, as well as in neurons of non-SCN regions. In SCN neurons, the currents
      evoked by 30 microM GABA were inhibited by Zn2+ with an IC50 of 50.3+/-3.2
      microM, whereas currents evoked by 100 microM GABA were inhibited with an IC50 of
      181.6+/-32.0 microM. The antagonist action of zinc saturated at 97.4+/-0.7% for
      30 microM GABA and 91.6+/-2.7% for 100 microM GABA. These observations indicate
      that Zn2+ inhibits SCN GABAA receptor competitively and in part non
      competitively. In SCN neurons, but not in other neurons, the zinc sensitivity
      varied with daily time. During the day, the calculated IC50 for zinc was
      significantly lower than during the night (43.9+/-4.7 microM vs. 58.6+/-3.8,
      respectively). These results indicate that native GABAA receptors in SCN neurons
      display pharmacological properties of receptors having and not having gamma
      subunit and that the proportionality of these receptors could change during the
      day and night.

PMID- 14667577
TI  - Iba1-expressing microglia respond to herpes simplex virus infection in the mouse
      trigeminal ganglion.
AB  - Microglial response in the trigeminal ganglion of mice corneally inoculated with
      herpes simplex virus (HSV) was investigated. Virus-infected neurons of the
      trigeminal ganglion did not exhibit apoptotic signal, while those of the
      trigeminal sensory brainstem nucleus did. Cells expressing ionized calcium
      binding adapter molecule 1 (Iba1), a specific marker of microglia/macrophages,
      increased in number in the virally infected region of the trigeminal ganglion,
      with morphological transformation to an activated phenotype, frequently detected
      as perineural satellites. Further microglial transformation to macropahges was
      not evident. Iba1-immunopositive perineural satellites also appeared in the
      vicinity of virally infected region. Such activated microglia expressed basic
      fibroblast growth factor (bFGF) molecules. The reverse transcription-polymerase
      chain reaction (RT-PCR) detected upregulated synthesis of mRNA for bFGF in the
      trigeminal ganglion. In contrast, in the trigeminal sensory brainstem nucleus, a
      small number of bFGF-producing cells appeared only in the vicinity of virally
      infected area. Collectively, Iba1-bearing microglia exist in the mouse trigeminal
      ganglion and respond to herpes simplex virus infection, most likely conferring
      neuroprotective functions upon the trigeminal ganglion.

PMID- 14667578
TI  - Dorz1, a novel gene expressed in differentiating cerebellar granule neurons, is
      down-regulated in Zic1-deficient mouse.
AB  - The Zic1 gene encodes a zinc finger protein that controls vertebrate neural
      development. A previous study showed that Zic1 is expressed in developing and
      mature cerebellar granule neurons, and that Zic1-deficient cerebellum is
      hypoplastic and lacks a lobule of the anterior lobe. In the present study, we
      searched for genes de-regulated in the cerebellum to understand the molecular
      basis of cerebellar development. A novel gene, Dorz1, was identified and
      characterized as one of the most significantly down-regulated genes in Zic1
      deficient cerebellum by the DNA microarray analysis. The expression of Dorz1 in
      the developing cerebellum peaked at embryonic day 17.5, and at that stage Dorz1
      transcripts were detected in cerebellar granule neuron precursors where Zic1
      expression is enhanced. In addition, Dorz1 expression was up-regulated in
      cultured cells overexpressing Zic1. These results suggest that Dorz1 expression
      is positively regulated by Zic1 during cerebellar development.

PMID- 14667579
TI  - Effect of acoustic stress on glucocorticoid receptor mRNA in the cochlea of the
      guinea pig.
AB  - As a first step toward elucidating the mechanism underlying the therapeutic
      effect of glucocorticoids on acute noise-induced hearing loss, we used
      semiquantitative reverse transcription polymerase chain reaction to study the
      level of glucocorticoid receptor (GR) mRNA in the cochlea of the guinea pig after
      acoustic overstimulation. The cochleas were dissected and divided into three
      portions (lateral portion, medial portion and modiolus). In the lateral portion,
      the glucocorticoid receptor mRNA level was significantly decreased 2 h after
      exposure to a 120 dB SPL sound and both 2 and 6 h after exposure to a 130 dB SPL
      sound. To determine where in the cochlea the changes in glucocorticoid receptor
      mRNA levels occur, in situ hybridization histochemistry was performed with
      digoxigenin-labeled sense and antisense RNA probes complementary to guinea pig
      glucocorticoid receptor mRNA. Glucocorticoid receptor mRNA was demonstrated in
      the spiral ligament, stria vascularis, spiral limbus and spiral ganglion.
      Moreover, the glucocorticoid receptor mRNA level was decreased in the spiral
      ligament, especially in the spiral prominence of the basal turn, 2 h after
      exposure to the 130 dB SPL sound. These results could imply that the therapeutic
      effect of glucocorticoids in the cochlea might be mediated in the spiral
      ligament, particularly in the spiral prominence.

PMID- 14667580
TI  - Modulation of the beta1-3 voltage-gated sodium channels in rat vestibular and
      facial nuclei after unilateral labyrinthectomy and facial nerve section: an in
      situ hybridization study.
AB  - We investigated whether the production of the mRNAs for the auxiliary beta
      subunits of the Na channels are modulated in deafferented medial vestibular
      nucleus (MVN) and in axotomized facial motoneurons. No beta1-3 mRNAs modulation
      was detected at any time following unilateral labyrinthectomy in the deafferented
      and intact medial vestibular nucleus. In contrast, beta1 gene expression in the
      axotomized facial nucleus decreased compared to controls as soon as day post
      lesion 3.

PMID- 14667581
TI  - Semi-quantitative expression analysis of ephrin mRNAs in the deafferented
      hippocampus.
AB  - To search for gene expression changes probably responsible for deafferentation
      induced reorganization in the brain, we have analyzed the expression of mRNAs for
      ephrin-A1, -A2, -A3, -A5 and -B1 in the rat hippocampus following transection of
      the entorhinal afferents by semi-quantitative reverse transcription polymerase
      chain reaction (RT-PCR). We found that their expression in the deafferented
      hippocampus increased significantly by 7 days, reached the maximum at 14 days and
      almost recovered to control levels by 60 days post-lesion. It is notable that the
      up-regulation of ephrin mRNAs occurs during the reorganization in the
      deafferented hippocampus, suggesting that ephrins may be involved in the
      plasticity events of the adult brain after lesion.

PMID- 14667582
TI  - Helix peptide immunoreactivity pattern in the nervous system of juvenile aplysia.
AB  - Distribution of neurons immunopositive to antibody against the small peptides
      encoded by the Helix Command-Specific 2 (HCS2) gene in the central nervous system
      of juvenile Aplysia californica was investigated. The HCS2 gene is specifically
      expressed in the withdrawal behavior neurons of the terrestrial snail Helix
      lucorum. In Aplysia, 20-25 immunopositive neuronal somata were observed on dorsal
      surface of each pleural ganglion (including a giant pleural neuron). The HCS2
      encoded peptide immunopositive fibers were observed in neuropiles of all ganglia
      and in many nerves. Functional significance of Aplysia immunopositive cells is
      discussed.

PMID- 14667583
TI  - Help wanted.

PMID- 14667584
TI  - Sleeve lobectomy or pneumonectomy: optimal management strategy using decision
      analysis techniques.
AB  - BACKGROUND: The choice between sleeve lobectomy and pneumonectomy is
      controversial for patients with early-stage lung cancer and who have acceptable
      lung function. METHODS: We performed a meta-analysis of results of sleeve
      lobectomy and pneumonectomy published in English from 1990 to 2003. A decision
      model was developed with 5-year survival, quality-adjusted life years (QALY), and
      cost effectiveness as the outcomes, and sensitivity analyses were performed.
      RESULTS: The model favored sleeve lobectomy (3.5 percentage point survival
      advantage) when the reward was 5-year survival; the results were influenced
      primarily by the 5-year survival rates for patients who did not develop recurrent
      cancer. Sleeve lobectomy was strongly favored when the reward was QALY (1.53 QALY
      advantage). Sleeve lobectomy was more cost effective than pneumonectomy, and had
      an incremental cost effectiveness ratio of $1,300/QALY. CONCLUSIONS: In patients
      with anatomically appropriate early-stage lung cancer, sleeve lobectomy offers
      better long-term survival and quality of life than does pneumonectomy and is more
      cost effective.

PMID- 14667585
TI  - Menopausal effects on presentation, treatment, and survival of women with non
      small cell lung cancer.
AB  - BACKGROUND: Small population studies have reported higher survival rates for
      women than men with non-small cell lung carcinoma (NSCLC). Because human NSCLC
      cells express estrogen receptors, we evaluated hormonally active and inactive
      women to identify biologically mediated differences. METHODS: A total of 14,676
      US women with stage I through IV primary non-small cell lung cancer (NSCLC) from
      the 1992 to 1997 Surveillance, Epidemiology, and End Results database were
      grouped into two categories based on the average menopausal age of 51 years as
      defined by the American College of Obstetricians and Gynecologists: ages 31 to 50
      premenopausal (n = 2,230, 15%) and ages 51 to 70 postmenopausal (n = 12,446,
      85%). Extreme ages were excluded. Statistics were calculated with chi(2) or Mann
      Whitney tests, Kaplan-Meier estimates with log-rank tests, and Cox proportional
      hazards models. RESULTS: Premenopausal women more commonly presented with
      advanced clinical stage, less favorable histology (adenocarcinoma), and poorly
      differentiated tumors, and more often underwent pneumonectomies. Surgery with
      curative intent was performed in 31% premenopausal and 33% postmenopausal women
      (p = 0.03). Overall survival for premenopausal and postmenopausal women was not
      significantly different (median 10 and 9 months, all stages; 70 and 71 months,
      stages I and II). Adjusting for significant covariates (stage, histology, size,
      grade, extent of surgery), postmenopausal women had higher lung-cancer-related
      deaths (hazard ratio, 1.14; 95% confidence interval, 1.03 to 1.27). CONCLUSIONS:
      Premenopausal women presented more often with advanced disease and underwent more
      extensive resection, yet had survival advantage after covariate adjustment.
      Additionally, postmenopausal women had a survival advantage compared with their
      male counterparts. Results suggest that estrogen exposure creates a milieu that
      may confer a protective effect through some yet unknown mechanisms that determine
      outcome of the neoplastic process and warrant further investigation.

PMID- 14667586
TI  - Lung resection for non-small-cell lung cancer in patients older than 70:
      mortality, morbidity, and late survival compared with the general population.
AB  - BACKGROUND: Operative mortality and morbidity in elderly patients operated on for
      non-small-cell lung cancer are acceptable. However, risk factors for hospital
      mortality and the benefits for the patients in the long term are insufficiently
      defined, and survival compared with the general population is not known. METHODS:
      From January 1989 to October 2001, 126 consecutive patients older than 70 years
      of age underwent resection for non-small-cell lung cancer. Each patient was
      scaled according to the Charlson Comorbidity Index. Postoperative events were
      divided into minor and major complications. Risk factors for complications and
      long-term survival were assessed by univariate and multivariate logistic
      regression analysis. Survival was compared with the yearly expected survival
      rates of the general population. RESULTS: The hospital mortality was 3.2%. Minor
      complications occurred in 71 (57%) patients, major complications, in 16 (13%)
      patients. No risk factor was predictive for major complications. However, a
      Charlson comorbidity grade of 3 to 4 was predictive for major complications (odds
      ratio, 12.6; 95% confidence interval, 1.5 to 108.6). Our study showed a 5- and 10
      year survival rate of 37% (95% confidence interval, 23 to 51) and 15% (95%
      confidence interval, 8 to 22). Smoking (odds ratio, 2.3), chronic obstructive
      pulmonary disease (odds ratio, 2.1), and pathologic stage IIIA (odds ratio, 2.2)
      or IIIB (odds ratio, 11.9) were risk factors for long-term survival. The observed
      survival was lower than the expected survival, but the difference decreased with
      increasing time after pulmonary resection. CONCLUSIONS: Pulmonary resection for
      non-small-cell lung cancer in patients older than 70 years shows acceptable
      morbidity and mortality. The Charlson index is a better predictor of
      complications than individual risk factors. In time survival is no longer
      correlated with the disease but follows the same pattern as the general
      population.

PMID- 14667587
TI  - Enduring challenge in the treatment of nonsmall cell lung cancer with clinical
      stage IIIB: results of a trimodality approach.
AB  - BACKGROUND: Stage IIIb (T4/N3) non-small-cell lung cancer (NSCLC) is considered
      an inoperable disease and treatment is an enduring challenge. Surgery after
      induction therapy seems to improve locoregional control. We report the results of
      a phase II prospective trimodality trial (chemotherapy and concomitant
      radiotherapy plus surgery) in patients with stage IIIb NSCLC. METHODS: From
      November 1992 to June 2000, 39 patients (37 men and 2 women, mean age 65 years)
      with clinical stage IIIb (34 T4N0 to 2, 4 T2 to 3N3, 1 T4N3, excluding T4 for
      malignant pleural effusion) entered the study. They received intravenous
      infusions of cisplatin 20 mg/m(2) and 5-fluorouracil 1,000 mg/m(2) (days 1 to 4
      and 25 to 28) combined with a total dose of 50.4 Gy radiotherapy delivered over 4
      weeks (1.8 Gy daily). Upon clinical restaging responders underwent surgery.
      RESULTS: All patients were available for clinical restaging. No complete response
      was observed. Twenty-one patients had partial response (53.8%), 16 had stable
      disease (41%), and 2 had progressive disease (5.2%). Hematologic toxicity was
      moderate. Twenty-two patients (56.4%), 21 with partial response and 1 with stable
      disease, underwent surgery with no perioperative death. A radical resection was
      possible in 21 cases. Nine lobectomies, 3 bilobectomies, and 9 pneumonectomies
      were performed. Complications occurred in 5 patients (23.6%). Fourteen of the
      patients who underwent surgery (66.6%) showed a pathologic downstaging. A
      complete pathologic response was obtained in 9 cases (49%). Overall 5-year
      survival (Kaplan-Meier) was 23%. Resected versus non-resected patients showed a
      significant difference: 38% versus 5.6% (p = 0.028, log rank). CONCLUSIONS: This
      trimodal approach for stage IIIb NSCLC appears safe and effective. It provides
      good therapeutic results with acceptable morbidity in surgical cases.

PMID- 14667588
TI  - Induction chemoradiotherapy and surgical resection for selected stage IIIB non
      small-cell lung cancer.
AB  - BACKGROUND: Combination chemotherapy using an oral combination of uracil and
      tegafur (UFT) plus cisplatin and concurrent thoracic radiotherapy is reported to
      have a high response rate and less toxicity for locally advanced non-small-cell
      lung cancer (NSCLC) patients. We performed a phase II trial using this
      chemoradiotherapy as an induction treatment. METHODS: Patients with marginally
      resectable stage IIIB NSCLC, an age younger than 70 years, a performance status
      of 0 or 1, and good organ function were eligible. The UFT (400 mg/m(2)) was
      administered orally on days 1 through 14 and 22 through 35 and cisplatin (80
      mg/m(2)) was injected intravenously on days 8 and 29. Radiotherapy with a total
      dose of 40 Gy was delivered in 20 fractions from day 1. A surgical resection was
      performed from 3 to 6 weeks after completing the induction treatment. RESULTS:
      Twenty-seven patients, 18 male and 9 female with a median age of 56 years and
      ranging from 36 to 69 years, were entered into the phase II trial. Clinical T4
      and N3 cancers were observed in 22 and 7 patients, respectively. Twenty-five
      (93%) achieved a partial response. The most frequently observed adverse event was
      grade 3 leukopenia in 26%. Of 25 patients who underwent a thoracotomy, 22 had a
      tumor resection. In all 22 patients a complex resection including a resection of
      the superior vena cava, carina, and vertebrae was required. Operative morbidity
      and mortality rates were 36% and 4% respectively. The calculated 1-year and 3
      year survival rates of all 27 patients were 73% and 56% respectively.
      CONCLUSIONS: Chemotherapy using UFT plus cisplatin and concurrent radiotherapy as
      induction treatment and a surgical resection for patients with marginally
      resectable stage IIIB NSCLC is feasible and promising. However it is difficult to
      conduct multi-institutional trials even for selected stage IIIB disease as a
      complex resection in almost all patients is necessary.

PMID- 14667590
TI  - Obstacles for shortening hospitalization after video-assisted pulmonary resection
      for lung cancer.
AB  - BACKGROUND: Video-assisted thoracic surgery for lung cancer facilitates early
      postoperative recovery when patients are treated by critical pathway management.
      Thus, we developed an original programmed regimen for postoperative management,
      evaluated the validity of this regimen, and analyzed clinical factors influencing
      postoperative recovery. METHODS: Forty consecutive patients with suspicious lung
      cancer undergoing anatomic pulmonary resection with video-assisted thoracic
      surgery were enrolled in this prospective study. After surgery, all patients who
      underwent anatomic resection were managed using our programmed regimen; a patient
      was considered recovered when the regimen had been completed. RESULTS: On final
      pathologic examination, 37 cases were determined to have lung cancer and
      underwent anatomic resection. The mean number of resected segments was 3.6. There
      were no complications caused by postoperative management. The mean day of
      postoperative recovery was 3.7 days and median, 3 days. Significant preoperative
      factors related to recovery were age, breathlessness, performance status,
      radiologic emphysema, partial pressure of arterial oxygen, and predictive
      postoperative forced expiratory volume in 1 second. The overall number of these
      risk factors was specifically related to postoperative recovery (p < 0.01): the
      rate of recovery on postoperative day 3 was 100% in patients with no risk, 68% in
      those with one to three risks, and 22% in those with four to six risks.
      CONCLUSIONS: Our original regimen is useful as a critical pathway for the
      management of lung cancer patients undergoing video-assisted thoracic surgery.
      Furthermore, we created specific criteria to identify risk factors related to
      postoperative recovery that may be useful in planning hospitalization for
      patients undergoing video-assisted thoracic surgery.

PMID- 14667591
TI  - Quality of life after tailored combined surgery for stage I non-small-cell lung
      cancer and severe emphysema.
AB  - BACKGROUND: We analyzed the early and long-term quality of life changes occurring
      in 16 patients undergoing tailored combined surgery for stage I non-small-cell
      lung cancer (NSCLC) and severe emphysema. METHODS: Mean age was 65 +/- 5 years.
      All patients had severe emphysema with severely impaired respiratory function and
      quality of life. Tumor resection was performed with sole lung volume reduction
      (LVR) in 5 patients, separate wedge resection in 3 patients, segmentectomy in 2
      patients, and lobectomy in 6 patients. A bilateral LVR was performed in 5
      patients. Quality of life was assessed at baseline and every 6 months
      postoperatively by the Short-form 36 (SF-36) item questionnaire. RESULTS: Mean
      follow-up was 44 +/- 21 months. All tumors were pathologic stage I. There was no
      hospital mortality nor major morbidity. Significant improvements occurred for up
      to 36 months in the general health (p = 0.02) domain and for up to 24 months in
      physical functioning (p = 0.02), role physical (p = 0.005), and general health (p
      = 0.01) SF-36 domains. Associated improvements regarded dyspnea index (-1.3 +/-
      0.6) forced expiratory volume in one second (+0.28 +/- 0.2L), residual volume (
      1.18 +/- 0.5L) and 6-minute-walking test distance (+86 +/- 67 m). Actuarial 5
      year survival was similar to that of patients with no cancer undergoing LVRS
      during the same period (68% vs 82%, p = not significant). CONCLUSIONS: Our study
      suggests that selected patients with stage I NSCLC and severe emphysema may
      significantly benefit from tailored combined surgery in terms of long-term
      quality of life and survival.

PMID- 14667592
TI  - Discrepancy of computed tomographic image between lung and mediastinal windows as
      a prognostic implication in small lung adenocarcinoma.
AB  - BACKGROUND: There have been no proven preoperative indicators for postoperative
      survival of patients with an adenocarcinoma, the incidence of which has been
      increasing lately. METHODS: Of 952 consecutive patients operated on for primary
      lung cancer between 1995 and 2002, 167 patients with a proven adenocarcinoma 3 cm
      or less in diameter underwent complete removal of the primary tumor. We examined
      their computed tomographic scans to estimate tumor shadow disappearance rate
      (TDR), which was defined as the ratio of the tumor area of the mediastinal window
      to that of the lung window, reviewed the clinical records, and evaluated their
      relation to prognosis. RESULTS: On univariate analyses, size of the tumor (p =
      0.0380), TDR (p = 0.0018), carcinoembryonic antigen (p = 0.0001) pathologic stage
      (p < 0.0001), nodal involvement (p < 0.0001), lymphatic invasion (p = 0.0001),
      and vascular invasion (p = 0.0017) were significantly associated with prognosis.
      Also, the outcomes of multivariate analyses for preoperative factors indicated
      that TDR (p = 0.0340) and carcinoembryonic antigen (p = 0.0047) are significant
      independent prognostic determinants. The 5-year survival was 48% in cases with a
      TDR of 0% to 25%, 87% in those with a TDR of 26% to 50%, 97% in those with a TDR
      of 51% to 75%, and 100% in those with a TDR of 76% to 100%. The incidence of
      lymphatic, vascular invasion, and nodal metastases was lower in patients with a
      higher TDR. CONCLUSIONS: Small-sized adenocarcinomas with a higher TDR showed
      less lymphatic, vascular vessel invasion, or nodal involvement, and demonstrated
      longer survival, suggesting that TDR was associated with clinical-pathologic
      characteristics and tumor aggressiveness. Preoperative assessment of TDR may be
      useful to identify an appropriate candidate for a lesser pulmonary resection.

PMID- 14667594
TI  - Basaloid carcinoma of the lung: a really dismal histologic variant?
AB  - BACKGROUND: Basaloid carcinoma of the lung has been reported as an uncommon and
      highly aggressive form of nonsmall cell lung cancers. Even in stage I and II of
      basaloid carcinoma, a 5-year survival rate of only 15% has been reported and it
      has been suggested that different treatment modalities for basaloid carcinoma
      should be considered. The aim of this study was to determine the prognostic
      implications of a basaloid carcinoma of the lung. METHODS: This study included a
      series of 291 surgically resected lung tumors, which were originally diagnosed as
      a poorly or undifferentiated carcinoma, a small cell carcinoma, or an atypical
      carcinoid. Of these, 35 basaloid carcinoma patients were identified and compared
      with 167 poorly differentiated squamous cell carcinoma (PDSC) patients in terms
      of the preoperative clinical data, the procedure performed, and the survival
      outcome. RESULTS: The overall incidence of basaloid carcinoma was 4.8%. The
      actuarial 5-year survival rate was 40.6% in patients with PDSC and 36.5% in those
      with basaloid carcinoma (p = 0.86). In stage I and II patients, the actuarial 5
      year survival rate was 53.9% in the PDSC group and 57.2% in the basaloid group (p
      = 0.97). There were no differences in the recurrence rate and the relapse pattern
      (p = 0.584). Cox's proportional hazards model revealed that an age equal to 60
      years old (hazard ratio 2.179, p = 0.000) and an advanced stage (hazard ratio
      2.264, p = 0.000) were the risk factors for postoperative survival in both
      groups. CONCLUSIONS: Basaloid carcinoma of the lung does not have a worse
      prognosis than the other nonsmall cell lung cancers. Although it is obvious that
      a basaloid carcinoma is a unique histologic entity, it does not require a
      different treatment modality due to the similar clinical behavior with other
      nonsmall cell lung cancers.

PMID- 14667595
TI  - Assessment of outcomes in typical and atypical carcinoids according to latest WHO
      classification.
AB  - BACKGROUND: Pulmonary carcinoid tumors represent a group of malignant neoplasms
      comprised of neuroendocrine cells. In 1999, the World Health Organization
      (W.H.O.) proposed the definitive classification of neuroendocrine tumors based on
      the criteria from Travis and associates. The W.H.O. described two different
      groups of carcinoid tumors: typical carcinoids (TC) and atypical carcinoids (AC).
      Few reports have reviewed their data according to the current classification, and
      therefore, prognosis and standard therapy for TC and AC are still uncertain.
      METHODS: From 1980 to 2001, 98 pulmonary resections have been performed for
      primary bronchial carcinoid tumors in our Thoracic Department of the University
      of Milan. We reviewed original histology using the current W.H.O. criteria and
      identified 88 patients with TC and 10 with AC. We reviewed the outcomes in each
      group. RESULTS: The 5 year-overall survival rate was 91.9% for TC and 71% for AC.
      The 10-year overall survival rate was 89.7% for TC and 60% for AC. The 5-year TNM
      related survival rates in the TC group were: IA-B, 100%; IIA-B, 75%; and IIIA,
      50%. At 10 years, they were: IA-B, 100%; IIA-B, 75%; and IIIA, 0%. The 5-year
      survival rates in the AC group were: IA-B, 100%; IIA-B, 100%; and IIIA, 0%. At 10
      years, they were: IA-B, 100%; IIA-B, 66%; and IIIA, 0%. CONCLUSIONS: Prognosis is
      favorable for both subtypes in the early stage. Advanced stages are related to
      better prognosis in TC. Recurrences rate is worse in the AC subtype. Our data
      suggest avoiding limited resections when feasible in AC. Parenchyma-sparing
      resections should be encouraged in TC.

PMID- 14667596
TI  - Management of the second episode of spontaneous pneumothorax: a decision
      analysis.
AB  - BACKGROUND: Optimal management for patients presenting a second episode of
      spontaneous pneumothorax remains controversial. The aim of this study was to
      compare two possible treatment strategies, video-assisted thoracic surgery (VATS)
      and conservative management, in order to assess which of the two was better
      adapted for the treatment of the second episode of spontaneous pneumothorax.
      METHODS: The authors propose a decision analytic model including a cost
      effectiveness study to compare two clinical strategies: VATS (reference strategy)
      and conservative management (alternative strategy). Data were obtained from a
      Medline search for English language articles and cost estimates were derived from
      the financial and public health departments of our hospital. The model was
      analyzed to determine the baseline strategy leading to the highest expected
      effectiveness and the lowest expected cost. RESULTS: Conservative management
      offered a slight advantage in expected effectiveness value (99.99 vs 99.93 for
      VATS). VATS produced the lowest expected cost (4347 vs 7536 for conservative
      management). The incremental cost-effectiveness ratio was 57,750. Within the
      ranges tested, the sensitivity analysis presented consistent results in terms of
      effectiveness and advocated conservative management as the best strategy. In
      terms of cost, with the exception of length of stay, the sensitivity analysis was
      insensitive in estimating the different probabilities, and favored VATS over
      conservative management. CONCLUSIONS: In the management of the second episode of
      spontaneous pneumothorax, VATS offers substantial savings in cost for only a
      slight decrease in effectiveness, when compared with conservative management.

PMID- 14667597
TI  - Intrapleural fibrinolytic treatment of multiloculated postpneumonic pediatric
      empyemas.
AB  - BACKGROUND: Progression of empyema, with the development of fibrinous adhesions
      and loculations, makes simple drainage difficult or impossible. The appropriate
      management remains controversial. Intrapleural fibrinolytic treatment to
      facilitate drainage of loculated empyema instead of open thoracotomy has been
      advocated since the 1950s. The aim of this study was to assess the effectiveness
      of intrapleural fibrinolytic treatment in postpneumonic pediatric empyemas.
      METHODS: In our clinic, we used intrapleural fibrinolytic agents in 72 pediatric
      patients with multiloculated empyema between 1994 and 2002. Streptokinase,
      250,000 U in 100 mL of 0.9% saline solution (59 patients), and urokinase, 100,000
      U in 100 mL of 0.9% saline solution (13 patients), were instilled daily into the
      chest tube, and the tube was clamped for 4 hours followed by suction. This
      treatment was continued daily for 2 to 10 days until resolution was demonstrated
      by chest radiograms or computed chest tomography. RESULTS: The rate of drainage
      after fibrinolytic treatment was increased 73.77%. Treatment was ineffective in
      14 (19.44%) of 72 patients who underwent fibrinolytic instillation. Treatment was
      discontinued because of allergic reaction and pleural hemorrhage in 1 patient,
      and because of development of bronchopleural fistula in another one. The regimen
      was completely successful in 43 (59.72%) patients, and partially successful in
      another 15 (20.83%). Twelve of those patients who had failure eventually required
      decortication and recovered completely. One patient died of sepsis and pleural
      hemorrhage; another patient died because of food aspiration. CONCLUSIONS: In all
      patients with loculations except those with a bronchopleural fistula,
      intrapleural fibrinolytic treatment should be tried. Thus, the majority of
      children with loculated empyemas can be treated successfully without invasive
      interventions, such as thoracoscopic debridements or open surgery.

PMID- 14667599
TI  - Is open thoracotomy still a good treatment option for the management of empyema
      in children?
AB  - BACKGROUND: The incidence of pediatric postpneumonic empyema increases, and there
      is little consensus on its management. Open thoracotomy has been linked with high
      morbidity and prolonged hospitalization. Our aim was to review the outcome after
      open thoracotomy and to provide a set of data for comparison with other treatment
      modalities. METHODS: Forty-four children (median age, 8 years, 2 months to 16
      years) undergoing surgery for postpneumonic empyema between 1993 and 2002 in our
      unit were studied. RESULTS: The median time from onset of symptoms to admission
      in a pediatric unit was 8 days (range, 2 to 63 days), the median time from
      pediatric admission to surgical referral was 3 days (range, 0 to 19 days), and
      the median time from surgical admission to thoracotomy was 1 day (range, 0 to 2
      days). Eight children had a chest drain before surgical admission. Six patients,
      who were referred late (19 to 69 days), had lung abscesses. A limited muscle
      sparing thoracotomy (44 patients), formal decortication (36 patients), lung
      debridement (5 patients), and lobectomy (1 patient) were performed. After
      thoracotomy, median time to apyrexia was 1 day (range, 0 to 27 days) and drain
      removal was 3 days (range, 1 to 16 days). A pathogen was isolated in 21 patients.
      There were no deaths. Four children with abscesses remained septic and had
      lobectomies (2 patients) and debridements (2 patients). The median postoperative
      hospital stay was 5 to 53 days. One child had postpneumonic empyema develop and
      had decortication 3 months postoperatively. At follow-up, all children were doing
      well and had satisfactory radiographs. The Kaplan-Meier 5-year and 10-year
      survival rate, freedom from any reoperation, and freedom from hospital
      readmission were 100%, 87%, and 98%, respectively. CONCLUSIONS: Open thoracotomy
      remains an excellent option for management of stage II-III empyema in children.
      When open thoracotomy is performed in a timely manner there is low morbidity and
      it provides rapid resolution of symptoms with a short hospital stay. However,
      delayed referrals may result in advanced pulmonary sepsis and a protracted
      clinical course. The late results are encouraging. Use of thoracoscopy or
      fibrinolysis should be considered on the basis of their own merit, not on the
      assumption of probable adverse outcomes after thoracotomy.

PMID- 14667600
TI  - Lymphogenous and hematogenous metastasis of thymic epithelial tumors.
AB  - BACKGROUND: A TNM classification has been established for various tumors.
      However, the TNM classification of thymic epithelial tumor has not been
      established yet. METHODS: We received replies to a questionnaire on thymic
      epithelial tumors from 115 institutes. We compiled a database of 1,320 patients
      with thymic epithelial tumor (1,093 thymomas, 186 thymic carcinomas, and 41
      thymic carcinoids) who were treated between 1990 and 1994. We used a tentative
      TNM classification of thymoma presented by Yamakawa and associates in 1991. The
      regional lymph nodes of the thymus were classified into three groups: anterior
      mediastinal lymph nodes (N1), intrathoracic lymph nodes (N2), and extrathoracic
      lymph nodes (N3). RESULTS: The rate of lymphogenous metastasis in thymoma, thymic
      carcinoma, and thymic carcinoid was 1.8%, 27%, and 28%, respectively. Most tumors
      with lymph node metastasis metastasized to N1 (thymoma, 90%; thymic carcinoma,
      69%; thymic carcinoid, 91%). The 5-year survival rates of N0, N1, and N2 thymoma
      were 96%, 62%, and 20%, respectively. The 5-year survival rates of N0, N1(,) N2,
      and N3 thymic carcinoma were 56%, 42%, 29%, and 19%, respectively. The 5-year
      survival rates of M0 and M1 thymoma were 95% and 57%. The 5-year survival rates
      of M0 and M1 thymic carcinoma were 51% and 35%. Multivariate analysis
      demonstrated that survival of patients with thymoma was dependent on the clinical
      stage of Masaoka and complete resection. In thymic carcinoma, survival was
      dependent on lymph node metastasis and complete resection. CONCLUSIONS: The N
      factor was one of the predictors of survival in thymoma and thymic carcinoma.
      However, M factor showed less influence on survival than T or N factors.

PMID- 14667602
TI  - Long-term outcome after multimodality treatment for stage III thymic tumors.
AB  - BACKGROUND: Surgery remains the cornerstone of therapy for thymic tumors, but the
      optimal treatment for advanced, infiltrative lesions is still controversial. The
      introduction of multimodality protocols has substantially modified survival and
      recurrence rate. We reviewed our 13-year prospective experience with
      multimodality treatment of stage III thymoma and thymic carcinoma. METHODS: Since
      1989 we have prospectively used a multimodality approach in 45 stage III thymic
      tumors. Sixteen patients (35%) had myasthenia gravis. Twenty-three patients (51%)
      had pure or predominantly cortical thymoma (group 1), 11 (24.5%) had well
      differentiated thymic carcinoma (group 2), and 11 (24.5%) had thymic carcinoma
      (group 3). Tumors that were not considered radically resectable at preoperative
      workup underwent biopsy and induction chemotherapy (15 patients, 33%) followed by
      surgical resection; all patients were referred for adjuvant chemoradiotherapy.
      RESULTS: No operative mortality was recorded; 1 treatment-related death during
      adjuvant chemotherapy was observed in group 1. Complete resection was feasible in
      91% of patients in groups 1 and 2 and 82% in group 3. The overall 10-year
      survival was 78%. Ten-year survival for groups 1 and 2 was 90% and 85%,
      respectively; 8-year survival for group 3 was 56%. During follow-up, tumor
      recurrence was noted in 3 patients (13%) from group 1, 3 (27%) from group 2, and
      3 (27%) from group 3. CONCLUSIONS: Multimodality treatment with induction
      chemotherapy (when required) and adjuvant chemoradiotherapy offers encouraging
      results for stage III thymic tumors; the outcome is more favorable for cortical
      thymoma and well-differentiated thymic carcinoma.

PMID- 14667603
TI  - Postoperative systemic artery to pulmonary vessel fistula: analysis of three
      cases.
AB  - BACKGROUND: Systemic artery to pulmonary vessel fistulas (SAPVF) occur through
      pleural adhesions from miscellaneous origin. We report 3 cases of acquired SAPVF
      that developed late after thoracotomy. METHODS: There was one pleurectomy for
      pneumothorax, one sleeve main bronchial resection, and one lower-middle
      bilobectomy. These SAPVF were discovered 4, 18, and 21 years after surgery.
      RESULTS: One patient underwent two unsuccessful embolizations. One patient
      underwent an unsuccessful attempt at surgical treatment after a previous
      embolization. Both have persistent SAPVF with minimal clinical discomfort 5 and
      13 years later. One patient remains without treatment. CONCLUSIONS: In the
      literature 13 cases of SAPVF have been reported after lung resection, pleural
      drainage, axillary abcess drainage, closed chest trauma, parietal pleurectomy,
      and talc poudrage. Potential treatments of SAPVF include embolization, resection
      of pleural adhesion, and artery ligation. The effectiveness of these techniques
      is uncertain and the follow-up is too short to draw any clear conclusions.
      Embolization seems to be a useful tool in case of a single afferent artery.
      Surgical treatment seems to achieve more durable results than embolization but
      carries a higher risk of bleeding in the case of large SAPVF. Because SAPVF are
      well tolerated and complications are uncommon, clinical follow-up may be
      warranted in most cases.

PMID- 14667604
TI  - Severe hyperhidrosis: clinical features and current thoracoscopic surgical
      management.
AB  - BACKGROUND: Severe hyperhidrosis is a debilitating disorder primarily affecting
      the palmar, plantar, and axillary regions. The purpose of our study was to review
      patient characteristics, surgical technique, and outcome of patients undergoing
      outpatient thoracoscopic sympathectomy for severe hyperhidrosis. METHODS: A
      series of 309 hyperhidrosis patients underwent thoracoscopy for T2-T3
      sympathectomy. Of these, 180 underwent prospective evaluation to more precisely
      identify pre- and postoperative features. RESULTS: The primary indication for
      surgery was palmar hyperhidrosis (PH) in 302 of 309 patients (97.7%), although in
      7 patients (2.3%) axillary hyperhidrosis (AH) was the primary indication. A
      family history was elicited in 74 of 132 (56.1%) and a provocative response to
      hand lotion was present in 101 of 132 (76.5%). Thoracoscopic sympathectomy
      afforded almost instantaneous cures for PH, with marked improvement in 100% for
      whom the sympathectomy was done. Of 180 patients prospectively questioned in
      detail, 173 (96.1%) had some degree of plantar hyperhidrosis. Of these, 148
      (84.4%) had some improvement, with 70 (40.5%) achieving complete relief of the
      plantar hyperhidrosis. In 98 patients who had some complaints of AH, 68 (69.4%)
      were completely relieved of the AH, while 25 (25.5%) were relieved but not
      completely cured. In 7 patients, the primary indication for sympathectomy was AH
      and of these, 3 (42.9%) had complete relief, 2 (28.6%) had partial relief, and 2
      (28.6%) had no relief. Of the entire series of 309 patients, 4 (1.3%) developed
      severe compensatory hyperhidrosis (CH). In 180 prospectively questioned patients,
      CH was present in 81 (45%). CONCLUSIONS: The most frequent presentation of
      hyperhidrosis involves the hands and feet. A family history of the disorder is
      common, and there is usually a provocative effect with hand lotion. Sympathectomy
      at the level of the T2-T3 ganglia is curative for PH, and in 80% of instances
      will improve plantar hyperhidrosis when in combination with PH. Sympathectomy for
      AH is not as effective as for PH. CH is common, occurring in nearly half, but
      only rarely is extreme and problematic. Bilateral thoracoscopic sympathectomy may
      be safely done as an outpatient procedure for most patients.

PMID- 14667605
TI  - Comparison of tracheal and nasal chondrocytes for tissue engineering of the
      trachea.
AB  - BACKGROUND: This study was undertaken to evaluate the feasibility of creating
      engineered tracheal equivalents grown in the shape of cylindrical cartilaginous
      structures using sheep nasal cartilage-derived chondrocytes. We also tested sheep
      tracheal and nasal septum for cell yield and quality of the engineered cartilage
      each produced. METHODS: Nasal septum and tracheal tissue were harvested from
      sheep. Chondrocytes from each were separately isolated from the tissues and
      suspended in culture media. Tracheal and nasal chondrocytes were seeded onto
      separate polyglycolic acid matrices. Cell-polymer constructs were cultured for 1
      week and then wrapped around a 7-mm diameter x 30-mm length silicon tube and
      implanted subcutaneously on the back of nude mice for 8 weeks (each, n = 6). Both
      of the tissue-engineered tracheas (TET) were harvested and analyzed for
      histological, biochemical, and biomechanical properties. These values were
      compared with native sheep trachea. RESULTS: The morphology and histology of both
      tracheal-chondrocyte TET and nasal-chondrocyte TET closely resembled that of
      native sheep trachea. Safranin-O staining showed that tissue-engineered cartilage
      was organized into lobules with round, angular lacunae, each containing a single
      chondrocyte. Chondrocytes from the trachea or nasal septum produced tissue with
      similar mechanical properties and had similar glycosaminoglycan and
      hydroxyproline content. CONCLUSIONS: This study demonstrates that the property of
      TET using nasal chondrocytes is similar to that obtained using tracheal
      chondrocytes. This has the potential benefit of facilitating an autologous
      approach for repair of segmental tracheal defects using an easily obtained
      chondrocyte population.

PMID- 14667606
TI  - Results with the freestyle porcine aortic root for right ventricular outflow
      tract reconstruction in children.
AB  - BACKGROUND: The ideal choice for valved reconstruction of the right ventricular
      outflow tract (RVOT) in children is undetermined. This study explores the
      Freestyle porcine aortic root for these patients. METHODS: From January 1998 to
      December 2002, 56 patients ages 1.6 to 29.9 years old (mean 11.8 years old)
      underwent RVOT reconstruction using a Freestyle porcine aortic root. The patients
      averaged 1.9 prior operations (range 0 to 5) for tetralogy of Fallot +/-
      pulmonary atresia (28 patients), critical pulmonary stenosis (10 patients), Ross
      procedure (5 patients), pulmonary atresia/intact ventricular septum (4 patients),
      complete atrioventricular septal defect +/- tetralogy of Fallot (4 patients), and
      others (5 patients). At time of RVOT reconstruction, 42 patients (75%) had
      additional procedures including the following: tricuspid or mitral repair (24
      patients), pulmonary arterioplasty +/- Glenn (12 patients), ventricular septal
      defect closure (5 patients), aortic valve replacement (3 patients), placement of
      a cardioverter/defibrillator or pacemaker (3 patients), and others (8 patients).
      RESULTS: One patient developed mediastinitis; another was treated for Candida
      endocarditis (his excised homograft unexpectedly grew Candida). All patients are
      well on follow-up from 2 to 60 months (mean 30 +/- 20 months) with no deaths. The
      patient with endocarditis underwent conduit replacement for recurrent pulmonary
      stenosis 3.5 years postoperatively. Echocardiography revealed mild or no
      pulmonary insufficiency in 93%. The calculated mean peak systolic RVOT gradient
      by echocardiography was 19.7 +/- 15.4 mm Hg. CONCLUSIONS: These data demonstrate
      excellent results with the Freestyle bioprosthesis for RVOT reconstruction in
      children. This valve may serve as a readily available alternative to homograft
      valves in RVOT reconstruction, particularly since early insufficiency seems to be
      less problematic. Questions of long-term durability and significance of
      echocardiographic stenosis remain unanswered.

PMID- 14667607
TI  - Medtronic freestyle valves in right ventricular outflow tract reconstruction.
AB  - BACKGROUND: Various pulmonary valve substitutes, with their inherent limitations,
      have been used in children and young adults. We chose the Medtronic Freestyle
      (Medtronics, Minneapolis, MN) valve because of its excellent hemodynamics, known
      durability in adults, and design features that allow modifications during
      implantation. METHODS: Over a 3 1/2 year period the Freestyle valve was implanted
      in 47 patients age 2 to 58 years (mean 14.2, median 12.0) in the pulmonary
      position. All patients had pulmonic stenosis and(or) insufficiency from previous
      operations for tetralogy (27), pulmonary atresia (6), truncus (4), or other
      diagnosis (10). The indication for surgery was pure pulmonary insufficiency in 11
      patients, pulmonic stenosis in 3, and mixed stenosis and insufficiency in 33.
      Root replacement technique was used with additional enlargement of the pulmonary
      artery branches in 10 patients. RESULTS: Intraoperatively, one patient sustained
      a right ventricle tear and one a circumflex coronary artery injury during the
      dissection. There was one postoperative death. Two patients developed late
      subvalvular pannus formation, one of whom required reoperation. One patient was
      found to have an echo gradient of 95 mm Hg due to decreased leaflet motion and
      underwent cardiac catheterization at which the peak systolic gradient was
      determined to be 50 mm Hg. He has not required reintervention during his 3 1/2
      years of follow-up. The remaining 43 patients have minimal gradients or
      insufficiency. All surviving patients are in New York Heart Association (NYHA)
      Class I. CONCLUSIONS: The Medtronic Freestyle valve is an attractive alternative
      for RVOT (right ventricular outflow tract) reconstruction in children. It is
      readily available, versatile, and has excellent hemodynamic characteristics.
      Although long term follow-up is not yet available, longevity of this prosthesis,
      and freedom from complications, will hopefully be superior to valves with stents.

PMID- 14667608
TI  - Risk factors for sudden death after repair of tetralogy of Fallot.
AB  - BACKGROUND: Sudden cardiac death remains the most common cause of death after
      repair of tetralogy of Fallot. It has been suggested that sudden cardiac death is
      related to right ventricular hypertrophy or dilation. However, it is uncertain
      whether the preoperative patient status or operative techniques predispose for
      sudden cardiac death. METHODS: From 1958 to 1977, 658 patients underwent repair
      of tetralogy of Fallot at our institution at a median age of 12.2 +/- 8.6 years.
      One third had at least one previous palliative operation 4.6 +/- 2.5 years
      earlier. A total of 490 patients survived the first postoperative year and were
      analyzed for sudden cardiac death. During a follow-up period of 25.3 +/- 5.8
      years (range, 1.0 to 35.5 years), 42 patients died, and 15 (36%) of those deaths
      were as a result of sudden cardiac death. RESULTS: Actuarial 10-year, 20-year,
      and 30-year survival rates were 97%, 94%, and 89%. Freedom from sudden cardiac
      death was 99%, 98%, and 95% after 10, 20, and 30 years. The risk of sudden
      cardiac death increased after 10 years from 0.06%/y to 0.20%/y. Univariate
      predictors (p < 0.1) of sudden cardiac death were use of an outflow tract patch
      (p = 0.068), male sex (p = 0.048), no previous palliation (p = 0.013), and higher
      preoperative New York Heart Association status (p = 0.014). Multivariate analysis
      confirmed these risk factors except use of an outflow tract patch. CONCLUSIONS:
      The most important risk factors for sudden cardiac death were higher preoperative
      New York Heart Association class and no previous palliation. Thus, early surgical
      intervention is recommended. The risk of sudden cardiac death increases with
      time, suggesting that long-term follow-up by specialized cardiologists or
      pediatricians should be intensified. However, all patients who died suddenly had
      at least two risk factors at the time of surgery.

PMID- 14667609
TI  - Commissural malalignment of aortic-pulmonary sinus in complete transposition of
      great arteries.
AB  - BACKGROUND: Translocation of the coronary artery to the neoaorta is essential in
      the arterial switch operation. The goal of this study is to investigate (1) the
      frequency of commissural malalignment in complete transposition of the great
      arteries, (2) the usefulness of echocardiography in diagnosis of commissural
      malalignment, and (3) the impact of commissural malalignment on surgery. METHODS:
      We retrospectively reviewed the medical records of 28 patients with complete
      transposition of the great arteries who underwent an arterial switch operation
      from February 2000 to August 2001. RESULTS: Commissural malalignment was expected
      preoperatively in 11 patients by echocardiography and was confirmed in 13
      patients intraoperatively. Four patterns of commissural malalignment were
      present: (1) sinus-facing of the pulmonary valve, (2) sinus-facing of the aortic
      valve, (3) sinus-facing of both valves, and (4) bicuspid pulmonary valve
      (functionally sinus-facing). Two patterns of severity were present: major and
      minor. To avoid torsion and stretching of the coronary arteries during surgery,
      various methods were needed: more extensive dissection of the coronary artery,
      trap door incision, supracommissural or juxtacommissural transfer, both coronary
      transfer to the same sinus, tube reconstruction of the coronary artery, and
      neoaorta dextrorotation anastomosis. One patient who had severe commissural
      malalignment died during the operation, and the cause of death was probably
      stretching or torsion of the coronary artery. CONCLUSIONS: The recognition of
      malalignment of the facing sinus in transposition of the great arteries can be
      detected preoperatively by echocardiography. The surgical procedure of the
      arterial switch operation is influenced by the presence of commissural
      malalignment. Preoperative awareness of commissural malalignment seems to be
      helpful for surgeons to predict the need for an alternative operational
      procedure.

PMID- 14667610
TI  - Cavopulmonary assist: circulatory support for the univentricular Fontan
      circulation.
AB  - BACKGROUND: Following Fontan palliation, the univentricular circulation is
      notable for coexisting systemic venous hypertension and pulmonary arterial
      hypotension. Assisted cavopulmonary blood flow to overcome this pressure gradient
      would restore the circulation to one more closely resembling normal two-ventricle
      physiology. We hypothesized that mechanical augmentation of cavopulmonary blood
      flow would provide physiologic stability in a model of cavopulmonary diversion
      and univentricular circulation. METHODS: Yearling sheep (n = 13, mean weight 56.5
      kg) underwent total cavopulmonary diversion on cardiopulmonary bypass. The
      superior and inferior vena cavae were anastomosed directly to the right pulmonary
      artery. Axial flow pumps were positioned within both vena cavae to assist blood
      flow from the systemic venous circulation into the pulmonary vasculature.
      Baseline ventilation was resumed, cardiopulmonary bypass was weaned, and pump
      support was titrated to obtain normal physiologic measurement. Cardiopulmonary
      data were collected for 6 hours. RESULTS: All animals demonstrated hemodynamic
      stability without need for volume loading, inotropic support, or pulmonary
      vasodilator therapy. Cardiac output, pulmonary vascular resistance, pulmonary
      arterial pressure, inferior vena caval pressure, and arterial pCO(2) and pO(2)
      values 6 hours after intervention were similar to baseline values. Arterial
      lactate levels steadily decreased throughout the cavopulmonary assist period.
      CONCLUSIONS: Cavopulmonary assist with a percutaneous pump provides physiologic
      stability in a model of total cavopulmonary diversion and univentricular Fontan
      circulation without altering regional volume distribution or cardiac output. This
      mode of circulatory support may have potential to benefit patients with marginal
      Fontan hemodynamics in both the early and late time periods.

PMID- 14667612
TI  - Effects of controlled antegrade pulmonary blood flow on cardiac function after
      bidirectional cavopulmonary anastomosis.
AB  - BACKGROUND: Bidirectional cavopulmonary anastomosis (BCPA) has been used as an
      intermediate stage in the treatment of patients with single-ventricle physiology.
      Leaving additional antegrade pulmonary blood flow has been shown to improve
      postoperative arterial blood oxygen saturations; however, controversy continues
      over whether the potential increase in systemic venous pressure is detrimental.
      We studied the effects of controlled antegrade pulmonary blood flow on cardiac
      function in patients after BCPA. METHODS: From January 1993 to July 2000, 128
      patients underwent BCPA. Mean age at operation was 6.2 +/- 4 months (range 2 to
      36 months). In group 1 (n = 72), restricted antegrade pulmonary blood flow was
      maintained through a native narrowed pulmonary valve or by adjustment of
      previously placed pulmonary artery band with the goal of maintaining the mean
      pulmonary artery pressure less than 16 mm Hg. In group 2 (n = 56), BCPA was the
      only source of pulmonary blood flow. RESULTS: One hospital death (0.8%) occurred.
      The mean pulmonary artery pressure at the end of the operation was 13 +/- 2 mm Hg
      in group 1 compared with 12 +/- 2 mm Hg in group 2, a difference that was not
      significant. Patients in group 1 had higher arterial oxygen saturations (84% +/-
      3% compared with 74% +/- 3% in group 2, p < 0.05), and shorter mean hospital stay
      (9 +/- 3 days compared with 15 +/- 2 days, p < 0.05). Persistent pleural effusion
      (> 10 days) or late chylothorax occurred in 4 patients from group 1 and 3 from
      group 2, a difference that was not significant. During a mean follow-up of 36 +/-
      10 months no late deaths occurred. The mean oxygen saturation remained higher in
      group 1, 80% +/- 3% compared with 74% +/- 4% in group 2, and the hematocrit was
      lower, at 38% +/- 3% compared with 46% +/- 4% (p < 0.05 for both comparisons).
      Cardiac catheterizations were performed in 68 patients before completion Fontan.
      Total pulmonary artery (Nakata) index was 263 +/- 34 mm(2)/m(2) in group 1 (n =
      40) and 188 +/- 13 mm(2)/m(2) in group 2 (n = 28) (p < 0.05). The mean pulmonary
      artery pressure and mean ventricular end-diastolic pressure were similar.
      CONCLUSIONS: Controlled antegrade pulmonary blood flow may have favorable effects
      on cardiac function for a selected group of patients and does not appear to have
      adverse effects on subsequent suitability for completion Fontan.

PMID- 14667614
TI  - Clipped tube fenestration after extracardiac Fontan allows for simple
      transcatheter coil occlusion.
AB  - BACKGROUND: Expensive devices are increasingly used to close a patent
      fenestration after a modified Fontan operation. We report our 5-year
      institutional experience of clipped tube fenestration after extracardiac Fontan
      operation, which allows for simple transcatheter coil occlusion. METHODS: We
      retrospectively reviewed 30 children, median age of 4.0 years (range, 2.4 to 8.8
      years) who underwent extracardiac Fontan operation between May 1996 and May 2001,
      and were fenestrated using a 4- to 8-mm diameter clipped tube graft. RESULTS: Ten
      children had a patent fenestration occluded by transcatheter placement of 15
      detachable coils (5- to 8-mm diameter). Aortic oxygen saturations increased on
      average by 5.5% (2% to 14%) and mean pressures in the Fontan circuit by 2.5 mm Hg
      (0 to 3 mm Hg). Four had immediate complete occlusion angiographically and 6 had
      trivial residual shunt, but complete occlusion by echocardiography at follow-up.
      There have been no immediate complications, late coil embolizations,
      thromboembolic events, or documented hemolysis within a follow-up after coil
      implantation of 1.7 years (0.4 to 4.5 years). Spontaneous fenestration closure
      was documented in 8 patients at cardiac catheterization and 9 patients by
      echocardiography with consistent improvement in resting transcutaneous oxygen
      saturation. Two children with a patent fenestration have been considered
      inappropriate for closure, and there was one early surgical death. There have
      been no complications related to the tube fenestration modification within a
      follow-up postoperation of 2.6 years (0.1 to 5.5 years). CONCLUSIONS: Clipped
      tube fenestration after extracardiac Fontan operation is a useful surgical
      modification that allows for simple transcatheter coil occlusion.

PMID- 14667615
TI  - Surgical resection of ventricular cardiac fibromas: early and late results.
AB  - BACKGROUND: Cardiac fibromas are rare tumors. Indications for and preferred type
      of operation are controversial, and little is known about early and late results
      of operation. METHODS: We retrospectively reviewed records of 18 patients who
      underwent resection of ventricular cardiac fibromas from 1964 to October 2002.
      Follow-up was obtained from current medical records and recent telephone and
      written correspondence. RESULTS: Seventeen patients had complete resection and 1
      had subtotal resection of one or more fibromas. Tumors were located in the left
      ventricle (n = 12), septum (n = 4), or right ventricle (n = 2). A 2-month-old
      infant died intraoperatively. None of the surviving 17 patients had complete
      heart block. Follow-up lasted up to 33.7 years for a total of 172.1 patient
      years. There were no late deaths. Fourteen patients were asymptomatic, 1 was in
      New York Heart Association functional class II, and 2 were in class III. There
      was no recurrence of tumor after complete resection and no change in size of
      residual tumor in the 1 patient who underwent subtotal resection. CONCLUSIONS:
      Although cardiac transplantation has been suggested by some as a preferable
      operation, most ventricular fibromas, even though extensive, can be completely
      resected with excellent early and late results. For patients with tumors
      extending into critical locations, subtotal excision can also give excellent late
      survival.

PMID- 14667616
TI  - Changing management of cardiac myxoma based on a series of 40 cases with long
      term follow-up.
AB  - BACKGROUND: Cardiac myxoma is generally considered to be a surgical emergency.
      However, as a result of progress in echocardiography and the increasing age of
      the patients presenting with this disease, the clinical presentation has changed
      and the management of cardiac myxoma now needs to be reviewed. METHODS: Between
      1978 and 2001, 40 patients (16 men and 24 women) between the ages of 6 months and
      82 years (mean age, 55.6 years) were operated on for cardiac myxoma. Signs of
      heart failure with pulmonary congestion (22%) or pulmonary embolism (20%)
      indicated a high-risk emergency situation in some cases, whereas, in other cases
      (58%), the patient's condition was stable and the clinical presentation was less
      worrying. However, the tumor was always removed within 24 hours of admission.
      Most cases of cardiac myxoma observed over the last decade correspond to stable
      forms, as echocardiography has revealed smaller tumors in generally elderly
      patients. RESULTS: The postoperative mortality was 7.5% (3 patients). No patients
      were lost to follow-up, and the mean follow-up was 13.6 years. One patient was
      reoperated for recurrence 3 years postoperatively. Five patients required further
      cardiac surgery: three mitral valve replacements, one coronary artery bypass
      graft, and one angioplasty. The 15-year survival rate was 69%. CONCLUSIONS:
      Myxoma tends to be observed in a more elderly and higher risk population, often
      at an early stage. The classic approach of emergency surgery is not always
      appropriate in these stable forms, allowing more thorough preoperative assessment
      of these patients.

PMID- 14667617
TI  - Long-term results of reoperative mitral valve surgery in patients with rheumatic
      disease.
AB  - BACKGROUND: Reoperative (redo) mitral valve surgery is still a continuing
      challenge to surgeons. The aim of this study was to detect the factors that
      affect late mortality or morbidity after redo mitral valve surgery in patients
      with rheumatic disease. METHODS: Between May 1983 and February 2003, 92 patients
      who underwent redo mitral valve surgery for rheumatic disease were enrolled. Risk
      factors influencing survival or cardiac events were investigated with univariate
      analysis and a Cox model. RESULTS: Operative mortality rate was 4.2%. Kaplan
      Meier actuarial analysis demonstrated an 84.7% 5-year, a 69.5% 10-year, and a
      65.9% 15-year survival. Multivariate analysis demonstrated that age at surgery
      and preoperative New York Heart Association (NYHA) class were found to be
      independent predictors of late deaths, and that higher age, advanced NYHA class,
      and previous mitral valve replacement were independent predictors of cardiac
      events. CONCLUSIONS: Redo mitral valve surgery can be achieved with low early
      mortality. However, long-term results of redo mitral surgery are not necessarily
      satisfactory in patients with preoperative advanced NYHA class or with a previous
      mechanical heart valve, and especially in 60 years or older age.

PMID- 14667619
TI  - Aorto-mitral annular dynamics.
AB  - BACKGROUND: The aortic and mitral valves are coupled through fibrous aorto-mitral
      continuity, but their synchronous dynamic physiology has not been completely
      characterized. METHODS: Seven sheep underwent implantation of five radiopaque
      markers on the left ventricle, 10 on the mitral annulus, and 3 on the aortic
      annulus. One of the mitral annulus markers was placed at the center of aorto
      mitral continuity (mitral annulus "saddle horn"). Animals were studied with bi
      plane videofluoroscopy 7 to 10 days postoperatively. Total circumference and
      lengths of mitral fibrous annulus, mitral muscular annulus, aortic fibrous
      annulus, and aortic muscular annulus were calculated throughout the cardiac cycle
      from three dimensional marker coordinates as was mitral annular area and aortic
      annular area. Aorto-mitral angle was determined as the angle between the centroid
      of the aortic annulus markers, the saddle horn, and the centroid of the mitral
      annulus markers. Aortic annulus and mitral annulus flexion was expressed as the
      difference between maximum and minimum values of the aortic and mitral annulus
      angles during the cardiac cycle. RESULTS: Mitral and aortic annular areas changed
      in roughly a reciprocal fashion during late diastole and early systole with an
      overall 32 +/- 8% change in aortic annular area and a 13 +/- 13% change in mitral
      annular area. Aortic fibrous annulus changed much less than aortic muscular
      annulus (6 +/- 2% vs 18 +/- 4%; p = 0.0003) as did mitral fibrous annulus
      relative to mitral muscular annulus (4 +/- 1% vs 8 +/- 2%; p = 0.004). Aortic
      annulus and mitral annulus flexion was 8 +/- 2 degrees and increased to 11 +/- 2
      degrees (p = 0.009) with inotropic stimulation. CONCLUSIONS: Dynamic aortic and
      mitral annular area changes were not mediated through the anatomic fibrous
      continuity. Aorto-mitral flexion, which increased with enhanced contractility,
      may facilitate left ventricle ejection. The effect of valvular surgical
      interventions on aorto-mitral flexion needs further investigation.

PMID- 14667620
TI  - Mortality and morbidity after total arch replacement using a branched arch graft
      with selective antegrade cerebral perfusion.
AB  - BACKGROUND: The early outcome after aortic arch surgery has improved. However,
      some operative survivors have died as a result of postoperative problems soon
      after discharge. This study determines the factors affecting mortality within 1
      year of total arch replacement. METHODS: Between July 1993 and November 2001, 103
      patients (mean age 65 +/- 11 years, 26 women, 35 dissections) underwent total
      arch replacement through a median sternotomy using a branched arch graft with
      selective cerebral perfusion. Eighteen operations including 14 acute dissections
      were performed on an emergency basis. Concomitant procedures were root
      replacement in 5 patients, mitral valve replacement in 1, coronary artery bypass
      in 14, and open endovascular stent-graft in 9. The average time (minutes) for
      bypass, aortic cross-clamp, selective cerebral perfusion, and distal arrest were
      respectively 273 +/- 79, 163 +/- 54, 145 +/- 36, and 69 +/- 22. RESULTS:
      Mechanical heart support was necessary in 3 patients. Stroke occurred in 9
      patients, transient neurologic dysfunction in 7, and paraplegia/paraparesis in 4.
      The only independent determinant for postoperative stroke was a history of stroke
      (odds ratio 16.3, 95% confidence interval: 2.8 to 93.8). Thirty-one patients
      required ventilator support for more than 5 days. Hemodialysis was needed in 5
      patients. Sternal infection or mediastinitis occurred in 6 patients. The in
      hospital mortality was 12% (12 of 103). The actuarial survival rate at 1 year was
      83%, and was 67% at 5 years. For the 1-year mortality independent determinants
      were emergency surgery (odds ratio 5.3, 95% confidence interval: 1.6 to 17.9) and
      age 75 years or older (odds ratio 4.0, 95% confidence interval: 1.1 to 13.9).
      CONCLUSIONS: Total arch replacement using a branched arch graft with selective
      antegrade cerebral perfusion has a favorable 1-year mortality rate except for
      patients undergoing emergency surgery and for elderly patients.

PMID- 14667621
TI  - Routine extended graft replacement for an acute type A aortic dissection and the
      patency of the residual false channel.
AB  - BACKGROUND: Recent surgical progress has had an impact on the mortality of acute
      type A aortic dissection. Routine aortic arch replacement, irrespective of the
      location of the intimal tears, may improve not only the outcome of the residual
      dissection but the operative mortality, because complete resection of intimal
      tears, including those invisible through the aortotomy in the ascending aorta is
      achieved. METHODS: During the past 7 years, total aortic arch replacement was
      performed in 50 consecutive patients with acute type A aortic dissection.
      Cerebral protection was achieved by deep hypothermia associated with
      pharmacologic cerebroplegia. Computed tomography and aortic angiography were
      performed to examine 48 patients for the possible presence of residual false
      channels before discharge. RESULTS: The duration of circulatory arrest ranged
      from 30 to 84 minutes. The hospital mortality was 10%, and a cerebral
      complication was observed in 1 patient. No evidence of a persisting false channel
      was detected in 27 patients (54%) who were totally thrombosed. During the follow
      up period (range: 2 months to 7 years), 2 patients died of hepatoma or pneumonia,
      respectively, and 2 patients underwent reoperation for recurrence of a dissection
      at the sinus of Valsalva. The Kaplan-Meier method estimated a 7-year survival of
      82%, and a 7-year freedom from reoperation of 93%. CONCLUSIONS: These results
      suggest that our aggressive use of routine aortic arch grafting can be
      accomplished with an acceptable risk and that our strategy not only improved the
      late results but the mortality associated with repairs for acute type A aortic
      dissection.

PMID- 14667622
TI  - Extraanatomic aortic bypass for repair of aortic arch coarctation via sternotomy:
      midterm clinical and magnetic resonance imaging results.
AB  - BACKGROUND: We analyzed our 22 years of experience with extraanatomic bypass
      grafting for repair of aortic arch coarctation in adults. Results from early and
      midterm follow-up with clinical evaluation and magnetic resonance angiography are
      reported. METHODS: Between November 1979 and December 2001, 18 consecutive
      patients aged 18 to 61 years (mean, 31.8 +/- 13.3 years) underwent extraanatomic
      bypass grafting to repair coarctation of the aortic arch. Six patients (33.3%)
      had recoarctation after previous repair through a left thoracotomy, and 3 (16.7%)
      had associated cardiac diseases. The operative technique used in all patients was
      ascending aorta-to-descending thoracic aorta bypass with a polyethylene
      terephthalate fiber (Dacron) graft through a median sternotomy and posterior
      pericardial approach. RESULTS: Follow-up was completed in all patients, with a
      mean duration of 5.6 +/- 5.7 years (range, 12 months to 22 years). The follow-up
      interval exceeded 10 years in 5 patients. No neurologic complications, early or
      late mortality, late reoperations, or graft complications occurred. Six patients
      (33.3%) had mild hypertension. All patients were asymptomatic with patent Dacron
      grafts confirmed by echocardiography. Magnetic resonance angiography, performed
      in 15 (83.3%) patients, revealed that the Dacron grafts were still patent at a
      mean interval of 4.0 +/- 6.2 years (range, 5 days to 22 years) after repair.
      CONCLUSIONS: Extraanatomic ascending aorta-to-descending thoracic aorta bypass
      grafting for repair of aortic arch coarctation in adults is safe, with low
      morbidity and no mortality. The favorable midterm results indicate this technique
      is a safe and less invasive means of repairing aortic arch coarctation or
      recoarctation in adults.

PMID- 14667623
TI  - Anatomical study of blood supply to the spinal cord.
AB  - BACKGROUND: Low incidences of spinal cord ischemia after thoracoabdominal aortic
      aneurysm repair, despite sacrifice of all segmental arteries, have recently been
      reported. This, however, cannot be explained by previous anatomical findings,
      which prompted us to perform an anatomical study of blood supply to the spinal
      cord. METHODS: Fifty-five spinal cords from Japanese formol-fixed cadavers (mean
      age, 79 +/- 10 years) were studied. Diameters of the anterior spinal artery (ASA)
      above and below the junction with the arteria radicularis magna (ARM) and
      diameters of the ARM were measured using the NIH image program (National
      Institutes of Health Image 1.58). RESULTS: The degree of narrowing of the ASA,
      defined as the diameter above the ARM expressed as a percentage of the diameter
      below the ARM, ranged from 23% to 161% and averaged 66% +/- 30%. The degree of
      narrowing was plotted against the ARM diameter divided by the ASA diameter above
      the junction to examine the impact of the degree of narrowing on distal spinal
      blood flow from the ARM. The degree of narrowing was related to distal spinal
      blood flow from the ARM (r= 0.56, p < 0.0001). CONCLUSIONS: The degree of
      narrowing of the ASA varies considerably. Furthermore, distal spinal blood supply
      becomes progressively dependent on the ARM as the narrow point of the ASA becomes
      narrower. These anatomical findings of spinal blood supply should be useful for
      elucidating the mechanisms of spinal cord injury after repair of extensive
      thoracoabdominal aneurysms.

PMID- 14667624
TI  - Cerebral physiology and outcome after hypothermic circulatory arrest followed by
      selective cerebral perfusion.
AB  - BACKGROUND: This study explored the impact of an interval of hypothermic
      circulatory arrest (HCA) preceding selective cerebral perfusion (SCP) on cerebral
      physiology and outcome. This protocol allows use of SCP during aortic surgery
      without the threat of embolization inherent in balloon catheterization of often
      severely atherosclerotic cerebral vessels. METHODS: In this blinded study, 30
      pigs (20 to 22 kg) were randomized after cooling to 20 degrees C. Pigs in the HCA
      CPB group (n = 10) underwent 30 minutes of HCA followed by 60 minutes of total
      body perfusion (CPB); HCA-SCP pigs (n = 10) underwent 30 minutes of HCA followed
      by 60 minutes of SCP, and SCP pigs (n = 10) had 90 minutes of SCP without prior
      HCA. Fluorescent microspheres enabled calculation of cerebral blood flow during
      perfusion and recovery. Hemodynamics, intracranial pressure, cerebrovascular
      resistance, and cerebral oxygen consumption were also monitored. Daily behavioral
      scores were obtained for 7 days postoperatively. RESULTS: In all groups, cerebral
      oxygen consumption fell significantly with cooling (p < 0.0001), remained low
      during perfusion, and rebounded promptly with rewarming; cerebral oxygen
      consumption was significantly (p = 0.027) greater during SCP than during HCA-CPB.
      Cerebral blood flow was significantly higher throughout SCP in the HCA-SCP group
      (p < 0.0001) than with CPB. Cerebrovascular resistance during SCP and HCA-SCP was
      significantly lower (p = 0.036) than during CPB. Behavioral scores were
      significantly better with SCP than with HCA-CPB throughout recovery, but did not
      differ between SCP and HCA-SCP. CONCLUSIONS: This study suggests that a short
      period of HCA preceding SCP provides global cerebral protection comparable to
      continuous SCP, implying that in clinical practice, a short period of HCA to
      reduce risk of embolization will not compromise the superior cerebral protection
      provided by SCP.

PMID- 14667625
TI  - Long-term results of cardiac transplantation in patients 65 years of age and
      older: a comparative analysis.
AB  - BACKGROUND: Advanced age is viewed by some transplant centers as a
      contraindication for heart transplantation secondary to concerns regarding
      decreased survival. METHODS: Between January 1992 and June 2002, 63 of 881 (7.2%)
      orthotopic heart transplants were performed in patients above 65 years. These
      patients were compared to 63 recipients below age 65 who were matched for sex,
      etiology of heart failure, United Network for Organ Sharing status, and
      immunosuppression therapy era. RESULTS: Mean age was 67.1 +/- 2.3 years (range,
      65.0 to 74.8) for the older group and 48.1 +/- 14.5 years (range, 18.3 to 64.4)
      for the younger group (p < 0.001). There was no significant difference in the
      incidence of diabetes, hypertension, chronic obstructive pulmonary disease, or
      peripheral vascular disease between the groups (p = not significant) although
      there were more patients with prior myocardial infarctions in the older group (p
      < 0.001). There was no significant difference in overall survival between the
      groups, with 1-, 3-, 5-, and 10-year actuarial survival of 85.8%, 80.3%, 73.1%,
      and 49.9% for the older group; and 86.9%, 83.4%, 75.0%, and 57.0% for the younger
      group (p = 0.597). Postoperative intensive care unit stay and overall hospital
      stay were similar for the two groups (p = not significant). There was no
      significant difference between the groups in freedom from infection or rejection
      at 1, 3, or 5 years after transplant (p = not significant) although the incidence
      of transplant coronary artery disease was higher in the older group (p = 0.025).
      CONCLUSIONS: These data demonstrate similar short-term and long-term results for
      elderly and young recipients undergoing cardiac transplantation. This supports
      proceeding with transplantation in carefully selected elderly patients.

PMID- 14667626
TI  - A multicenter comparison of intraaortic balloon pump utilization in isolated
      coronary artery bypass graft surgery.
AB  - BACKGROUND: Single-center studies suggest substantial variation in intraaortic
      balloon pump (IABP) utilization. Our purpose is to examine IABP utilization over
      time and across medical centers. METHODS: This was a prospective cohort of 29,961
      consecutive patients undergoing isolated coronary artery bypass graft surgery,
      between 1995 and 2000, at 10 centers (eight in northern New England and two in
      Canada). RESULTS: A total of 2,678 (8.9%) patients received an IABP. The rate of
      preoperative IABP insertion was 6.3%, and that of intra- or postoperative
      insertion was 2.6%. During the 6 years, IABP use increased from 7.0% to 10.3%
      (p(trend) <0.001). Preoperative IABP insertion increased from 5.4% to 7.8%
      (p(trend) < 0.001). There was no significant increase in intra-/postoperative
      IABP insertion 1.7% to 3.4% (p(trend) = 0.34). Adjustment for changes in patient
      and disease characteristics did not substantially alter these results. The rate
      of IABP use varied substantially by center, from 5.9% to 16.4% (p < 0.001).
      Adjustment for patient and disease characteristics resulted in variation from
      4.8% to 12.8% across the 10 centers (p < 0.001). The adjusted rates of
      preoperative IABP insertion varied from 3.6% to 13.7% (p < 0.001), and the rates
      of intra-/postoperative IABP insertion ranged from 1.0% to 5.2% (p < 0.001).
      There was no significant correlation between the rates of preoperative and intra
      /postoperative IABP use (r(s) = 0.085, p = 0.815). CONCLUSIONS: During the 6
      years, there was a 47% increase in the rate of IABP utilization. Even after
      adjustment, there was almost threefold variation in IABP use across centers. This
      variation likely reflects lack of consensus on the appropriate use of the IABP in
      CABG patients.

PMID- 14667628
TI  - Risk factor analysis of Swedish Left Ventricular Assist Device (LVAD) patients.
AB  - BACKGROUND: The use of left ventricular assist devices (LVADs) is established as
      a bridge to heart transplantation. METHODS: All Swedish patients on the waiting
      list for heart transplantation, treated with LVAD since 1993 were retrospectively
      collected into a database and analyzed in regards to risk factors for mortality
      and morbidity. RESULTS: Fifty-nine patients (46 men) with a median age of 49
      years (range, 14 to 69 years), Higgins score median of 9 (range, 3 to 15),
      EuroScore median of 10 (range, 5 to 17) were investigated. Dominating diagnoses
      were dilated cardiomyopathy in 61% (n = 36) and ischemic cardiomyopathy in 18.6%
      (n = 11). The patients were supported with LVAD for a median time of 99.5 days
      (range, 1 to 873 days). Forty-five (76%) patients received transplants, and 3
      (5.1%) patients were weaned from the device. Eleven patients (18.6%) died during
      LVAD treatment. Risk factor analysis for mortality before heart transplantation
      showed significance for a high total amount of autologous blood transfusions (p <
      0.001), days on mechanical ventilation postoperatively (p < 0.001), prolonged
      postoperative intensive care unit stay (p = 0.007), and high central venous
      pressure 24 hours postoperatively and at the final measurement (p = 0.03 and
      0.01, respectively). Mortality with LVAD treatment was 18.6% (n = 11). High C
      reactive protein (p = 0.001), low mean arterial pressure (p = 0.03), and high
      cardiac index (p = 0.03) preoperatively were risk factors for development of
      right ventricular failure during LVAD treatment. CONCLUSIONS: The Swedish
      experience with LVAD as a bridge to heart transplantation was retrospectively
      collected into a database. This included data from transplant and nontransplant
      centers. Figures of mortality and morbidity in the database were comparable to
      international experience. Specific risk factors were difficult to define
      retrospectively as a result of different protocols for follow-up among
      participating centers.

PMID- 14667630
TI  - Early and medium-term results after on-pump and off-pump coronary artery surgery:
      a propensity score analysis.
AB  - BACKGROUND: Comparative publications on beating-heart off-pump coronary artery
      bypass grafting (OPCAB) surgery versus conventional coronary artery bypass
      grafting (CCAB) surgery frequently do not offer conclusive information because of
      investigator bias. METHODS: Trying to eliminate this problem, a propensity score
      analysis of the data of all CCAB patients (n = 517) and OPCAB patients (n = 133)
      operated on by the same surgeons during the same time period (1998 to 2001) was
      applied. After matching patients with similar propensity score values, 97 CCAB
      patients and 72 OPCAB patients entered the final analysis. RESULTS: Early results
      were similar in both groups: the 30-day mortality reached 1.4% in the CCAB group
      and 2.8% in the OPCAB group; strokes did not happen. Perioperative myocardial
      infarctions occurred in 4.1% of the CCAB patients and 4.3% of the OPCAB patients.
      Drainage blood loss in the first 24 hours after surgery (830 +/- 687 mL, CCAB
      group; and 909 +/- 678 mL, OPCAB group) was similar (p = 0.06) in both groups.
      Medium term results (freedom from percutaneous transluminal coronary angioplasty
      or reoperation, freedom from myocardial infarction, freedom from stroke, and the
      quality of life) also were not significantly different between the off-pump and
      on-pump groups after a mean follow-up of 27 +/- 11 months. CONCLUSIONS: Our
      results suggest that elective-surgery patients with coronary artery disease can
      be operated on either on-pump or off-pump with the same early and late mortality
      and morbidity.

PMID- 14667631
TI  - Preoperative C-reactive protein and outcome after coronary artery bypass surgery.
AB  - BACKGROUND: C-reactive protein (CRP) is a predictor of early and late outcome
      after coronary angioplasty, but there is scant data on its impact on the outcome
      after coronary artery bypass grafting (CABG). METHODS: The predictive value of
      preoperative CRP was evaluated in a series of 764 patients who underwent on-pump
      CABG. RESULTS: During the in-hospital stay, 13 patients (1.7%) died, 45 (4.5%)
      developed low cardiac output syndrome, and 28 (3.7%) suffered minor or major
      cerebrovascular complications. Patients with a preoperative serum concentration
      of CRP>/=1.0 mg/dL had a higher risk of overall postoperative death (5.3% vs
      1.1%, p = 0.001), cardiac death (4.4% vs 0.8%, p = 0.002), low cardiac output
      syndrome (8.8% vs 3.7%, p = 0.01), and any cerebrovascular complication (4.4% vs
      3.5%, p = 0.66). Preoperative serum concentration of CRP>/=1.0 mg/dL was
      significantly more frequent among patients with history of myocardial infarction,
      diabetes, lower limb ischemia, low left ventricular ejection fraction, NYHA class
      IV, and in those undergoing urgent or emergency operation. At multivariate
      analysis, preoperative serum concentration of CRP >/= 1.0 mg/dL (p = 0.01, O.R.:
      6.97) and left ventricular ejection fraction (p = 0.01, O.R.: 0.95) were
      independent predictors of postoperative death. Postoperative mortality rate was
      0.3% among patients with preoperative CRP < 1.0 mg/dL and an ejection fraction
      >/=50%, whereas it was 21.4% among those with a preoperative CRP >/= 1.0 mg/dL
      and an ejection fraction less than 50% (p < 0.0001). CONCLUSIONS: Preoperative
      serum concentration of CRP in patients undergoing on-pump coronary artery bypass
      surgery is an important determinant of postoperative outcome.

PMID- 14667632
TI  - Our experiences for off-pump coronary artery bypass grafting to the circumflex
      system.
AB  - BACKGROUND: Complete revascularization has been difficult in off-pump coronary
      artery bypass grafting (OPCAB). Hemodynamic deterioration often prevents access
      to the circumflex territory. This study presents instrumentation for accessing
      the circumflex territory, and our clinical experience. METHODS: From August 1999
      through December 2002, 140 patients underwent OPCAB via sternotomy in our
      institution. The 114 requiring reconstruction of the circumflex artery are the
      subjects of this study. There were no exclusion criteria. A series of techniques
      and instruments were developed to provide access to the circumflex area while
      hemodynamic stability was preserved, including the left pericardial traction
      technique, compression of the right pericardium, a right sternal retractor, and a
      type of shunt tube. RESULTS: Patients received an average of 3.2 grafts (range, 2
      to 6). Complete revascularization was achieved in 95% of the cases. Complications
      included respiratory insufficiency (0.8%), renal dysfunction (7%), and sternal
      wound infection (0.8%). Blood transfusions were required in 10 patients (8%). No
      patient suffered perioperative myocardial infarction or stroke. No operation was
      converted to cardiopulmonary bypass. There was no operative death. Predischarge
      angiography demonstrated a 99% patency rate. CONCLUSIONS: With our techniques and
      instruments, off-pump coronary revascularizaion of the circumflex area may be
      performed safely to achieve complete revascularization. Early clinical results
      are excellent, but long-term longitudinal follow-up is required to assess the
      future effectiveness of OPCAB procedure with our techniques.

PMID- 14667633
TI  - Risks and benefits of bilateral internal thoracic artery grafting in diabetic
      patients.
AB  - BACKGROUND: There is a tendency to avoid the bilateral internal thoracic artery
      (ITA) grafting in diabetics. However, we no longer consider diabetes a reason for
      excluding the bilateral use of ITAs. We compare the early and long-term results
      in diabetic cases treated by coronary artery bypass grafting (CABG) using
      unilateral and bilateral ITA grafts. METHODS: A total of 303 consecutive diabetic
      cases of CABG using ITA grafts between April 1991 and January 2003 were reviewed.
      Of these, 149 (49%) were being treated with insulin. The cases were divided into
      two groups: 179 cases in which bilateral ITA grafts had been used and 124 in
      which a unilateral ITA graft had been used. RESULTS: The mortality for the
      bilateral ITA group and unilateral ITA group were 1.7% and 1.6%, respectively.
      The fact that patients were receiving insulin had no effect on the mortality of
      CABG. A review of morbidity revealed that no differences were found between the
      two groups. The survival curves, cardiac-death-free curves, and cardiac-event
      free curves showed that there was no difference between the use of one or two ITA
      grafts in diabetics, while bilateral use of ITA grafts was significantly better
      than unilateral use in a comparable group of nondiabetics operated during the
      same time period. CONCLUSIONS: There was no significant difference in operative
      mortality related to single or double ITA grafting in diabetics. There was also
      no difference between the use of one or two ITA grafts in diabetics in regard to
      long-term follow-up.

PMID- 14667634
TI  - Differential in vitro response of the human radial artery versus left internal
      thoracic artery to cerivastatin: implications to bypass grafting.
AB  - BACKGROUND: This study investigated acute (in vitro) and long-term (in vivo)
      effects of statins on the vascular function of human radial artery (RA) and left
      internal thoracic artery (LITA). METHODS: RA and LITA specimens were divided into
      vascular rings, which were incubated in the absence or presence of 10(-6) mol/L
      Cerivastatin for 2 or 24 hours. In terms of preoperative statin treatment, four
      groups included: group 1 [preop statin(-)/in vitro cerivastatin(-)]; group 2
      [preop(-)/in vitro(+)]; group 3 [preop(+)/in vitro(-)]; and group 4 [preop(+)/in
      vitro(+)]. Endothelial function was assessed with acetylcholine (10(-9) to 10(-5)
      mol/L) following contraction by 3 x 10(-8) mol/L endothelin-1. RESULTS: Although
      endothelium-dependent vasodilatation was higher in RA (57.7% +/- 3.5%) than in
      LITA (46.5% +/- 3.8%, p = 0.046), there was no significant evidence that it
      depended on the preoperative use of statins or incubation period. In vitro
      incubation with cerivastatin significantly increased endothelium-dependent
      vasodilatation by 14.2% +/- 2.4% (p < 0.0001) independent of artery types
      (RA/LITA). There was no significant evidence that endothelium-dependent
      vasodilatation depended on the preoperative use of statins or incubation period.
      CONCLUSIONS: In vitro incubation with cerivastatin preserved endothelial function
      more effectively than preoperative use of statins. This could have implications
      to perioperative use of statins for patients undergoing coronary surgery.

PMID- 14667635
TI  - Limitations for manual and telemanipulator-assisted motion tracking--implications
      for endoscopic beating-heart surgery.
AB  - BACKGROUND: Surgical performance is limited by human factors. Beating-heart
      surgery requires full dexterity and motion tracking. Currently techniques for
      total endoscopic beating-heart bypass grafting using telemanipulation systems are
      being developed. The aim of this study was to assess the limitations for manual
      and telemanipulator-assisted motion tracking using the da Vinci telemanipulator
      system. METHODS: To simulate beating-heart conditions an endoscopic trainer was
      developed. Twenty subjects were asked to touch targets manually and with
      telemanipulator assistance with different patterns of increasing index of
      difficulty (resting model, unstabilized, and stabilized model with a frequency of
      35, 60, and 90 beats per minute). In addition one task was performed using
      different scaling ratios on a resting model. The times between hits as well as
      errors were electronically recorded. RESULTS: There was no significant impact of
      various frequencies and amplitudes for manual tracking. The average values for
      the delay (k(m)[ms]) and information-processing (c(m) [ms/bit]) constants for the
      manual tasks were 201 ms and 86 ms/bit respectively. Both the delay constant
      (k(t) = 630 ms; p < 0.0005) and the information-processing constant (c(t) = 250
      ms/bit; p < 0.0005) were increased for the telemanipulator-assisted tasks at
      rest. When working on moving targets telemanipulator-assisted tracking required
      significantly more time and led to more errors. At a frequency of 90 beats per
      minute telemanipulator-assisted tracking became more difficult. CONCLUSIONS:
      Endoscopic beating-heart bypass grafting requires optimal stabilization to avoid
      inaccuracies due to incomplete motion tracking. At higher frequencies
      telemanipulator-assisted tracking became more difficult, demonstrating the
      technical limits of current telemanipulator technology.

PMID- 14667638
TI  - Successful diagnosis of penetrating cardiac injury using surgeon-performed
      sonography.
AB  - BACKGROUND: Patients with penetrating cardiac injuries have a high mortality. The
      utilization of sonography in these patients may lead to earlier diagnosis and
      definitive surgical intervention. METHODS: A retrospective review of all patients
      admitted to a level I trauma center were examined from March 1996 to March 2001
      (17,241 patients). Patients were identified with penetrating thoracic injuries
      and were evaluated for mechanism of injury, sonographic findings (subxiphoid and
      parasternal windows), injury severity score, length of stay, and mortality.
      Surgeons performed all sonography. RESULTS: There were 478 patients who underwent
      sonography for penetrating thoracic injuries. Twenty-three patients were
      identified with positive sonographic findings. Subsequently 20 patients had a
      cardiac injury at surgery. There were no missed injuries. The 3 patients with
      false positive findings had congestive heart failure (2 patients) and morbid
      obesity (1 patient). Mean time to operation was 13 minutes. Mean injury severity
      score was 33. Mean intensive care unit and hospital stay was 3.1 days and 7.2
      days respectively. Sonography had a specificity of 99.3% and sensitivity of 100%
      for identifying penetrating cardiac injury and a positive predictive value of 87%
      and negative predictive value of 100%. There were no hospital deaths.
      CONCLUSIONS: Early diagnosis and management using surgeon performed sonography
      may reduce the high mortality associated with penetrating cardiac injury.

PMID- 14667637
TI  - Perioperative changes in cerebral blood flow after cardiac surgery: influence of
      anemia and aging.
AB  - BACKGROUND: Stroke occurs in 2% to 5% and cognitive dysfunction occurs acutely in
      60% to 80% of patients early after cardiac surgery. Both may have long-term
      consequences. Research into mechanisms behind these sequelae has been focused
      intraoperatively, although there is little reason to believe that injury is
      limited to this period. Aging prominently increases the incidence of these
      sequelae. Anemia with cardiac surgery is acute and severe, should cause an
      increase in cerebral blood flow (CBF), and may impact stroke and cognitive
      function in this setting. To better understand changes in perioperative CBF
      physiology we have measured changes in CBF and the influence of anemia and aging
      on these changes. METHODS: Cerebral blood flow was measured using the noninvasive
      continuous arterial spin labeling perfusion magnetic resonance imaging method.
      Cerebral blood flow, mean arterial pressure, hemoglobin, hemoglobin oxygen
      saturation, and cardiopulmonary bypass time were recorded in 12 subjects before
      and 6 +/- 2 days after cardiac surgery. RESULTS: Cerebral blood flow increased
      from 44.6 +/- 15.6 mL100 g(-1)min(-1) to 64.4 +/- 20.1 mL100 g(-1)min(-1) after
      cardiac surgery, or 49.1% +/- 26.7%, (p < 0.0001). The absolute change in CBF
      (DeltaCBF) was predicted by the following regression model: DeltaCBF = -55 +
      0.64(Age) + 0.53(CBF(Pre)) -3.3(DeltaHgb); R(2) = 0.81; p = 0.003, where CBF(Pre)
      is the baseline preoperative CBF and DeltaHgb is the change in hemoglobin from
      preoperative to postoperative periods. CONCLUSIONS: Cerebral blood flow increases
      after cardiac surgery, and anemia appears to be an important cause. Age appears
      also to be an important covariate, with advancing age further increasing the
      magnitude of this hyperemia. The interrelationship of aging and anemia, in
      determining perioperative changes in CBF, and potentially cerebral oxygenation,
      may have important implications for the understanding of perioperative stroke and
      cognitive dysfunction after cardiac surgery.

PMID- 14667639
TI  - Deep sternal wound infection: a sternal-sparing technique with vacuum-assisted
      closure therapy.
AB  - BACKGROUND: Vacuum-assisted closure therapy is a novel treatment employed to aid
      wound healing in different areas of the body and recently also in sternotomy
      wounds. Aggressive vacuum-assisted closure treatment of the sternum in
      postoperative deep wound infection enhances sternal preservation and the rate of
      possible rewiring. METHODS: The records of 40 consecutive patients with deep
      sternal wound infection were reviewed. Sternal bone sparing was achieved by using
      layers of paraffin gauze (Jelonet; Smith and Nephew Medical, Hull, UK) at the
      bottom of the wound in order to cover and protect visible parts of the right
      ventricle, lung tissue, and grafts from the sternal edges. Two separate layers of
      polyurethane foam (KCI, Copenhagen, Denmark) were placed so as to fit between the
      sternal edges and subcutaneously. A continuous negative pressure of 125 mm Hg was
      applied and subsequent revision was made exclusively in nongranulation areas.
      RESULTS: There were no deaths during the 90 days of follow-up. Three late deaths
      unrelated to the infection and three subcutaneous fistulas occurred during the
      total follow-up period (3 to 41 months). The median duration of the vacuum
      assisted closure therapy was 10 days (range, 3 to 34). The series represents a
      total of 474 days with the vacuum-assisted closure device without serious adverse
      events. CONCLUSIONS: In our opinion this modified vacuum-assisted closure therapy
      is a safe and reproducible option to bridge patients with postoperative deep
      sternal wound infection to complete healing. Reconstruction of the sternum was
      achieved in all patients without the use of muscle or omental flap surgery.

PMID- 14667641
TI  - Modulation of calcium transport improves myocardial contractility and enzyme
      profiles after prolonged ischemia-reperfusion.
AB  - BACKGROUND: Ischemia-reperfusion (IR) injury causes myocardial dysfunction in
      part through intracellular calcium overload. A recently described pharmacologic
      compound, MCC-135 (5-methyl-2-[1-piperazinyl] benzenesulfonic acid monohydrate,
      Mitsubishi Pharma Corporation), alters intracellular calcium levels. This project
      tested the hypothesis that MCC-135 would influence regional myocardial
      contractility when administered at reperfusion and after a prolonged period of
      ischemia. METHODS: A circumflex snare and sonomicrometry crystals within remote
      and area-at-risk regions were placed in pigs (n = 18, 32 kg). Coronary occlusion
      was instituted for 120 minutes followed by 180 minutes of reperfusion. At 105
      minutes of ischemia pigs were randomly assigned to IR only (n = 11) or MCC-135
      (IR-MCC [300 microg. kg(-1). h(-1), n = 7]) administered intravenously. Regional
      myocardial contractility was determined by calculation of the regional end
      systolic pressure-dimension relation (RESPDR [mm Hg/cm]). Myocardial injury was
      determined by measurement of plasma levels of myocyte-specific enzymes. RESULTS:
      At 90 minutes ischemia, mean troponin-I was 35 +/- 8 ng/mL with no significant
      difference between groups. At 180 minutes reperfusion, heart rate was increased
      by 18% +/- 5% in the IR only group (p < 0.05) and was reduced by 11% +/- 4% with
      IR-MCC (p < 0.05). At 90 minutes ischemia RESPDR was reduced from baseline by 51%
      +/- 6% (p < 0.05). By 30 minutes reperfusion, reductions in RESPDR were
      attenuated with IR-MCC compared with IR only values. The CK-MB levels were
      increased at 180 minutes reperfusion in the IR only group (52 +/- 9 ng/mL)
      compared with baseline (6 +/- 1 ng/mL, p < 0.05) but were attenuated with IR-MCC
      (24 +/- 4 ng/mL, p < 0.05) compared with IR only values. CONCLUSIONS: Despite
      similar degrees of injury at 90 minutes ischemia MCC-135 improved regional
      contractility and reduced the egress of CK-MB. Moreover MCC-135 was associated
      with decreased heart rate, a determinant of myocardial oxygen demand.
      Pharmacologic modulation of calcium transport ameliorates myocardial dysfunction
      in the acute IR period.

PMID- 14667643
TI  - Cell transplantation to prevent heart failure: a comparison of cell types.
AB  - BACKGROUND: Autologous cell transplantation may restore viable muscle after a
      myocardial infarction. We compared the effect of three cell types or an
      angiotensin-converting enzyme (ACE) inhibitor on preservation of ventricular
      function after cardiac injury. METHODS: A uniform transmural myocardial scar was
      created in adult rats by cryoinjury. Three weeks later the rats were randomly
      assigned to one of four blinded treatments: transplantation with 5 x 10(6) aortic
      smooth muscle cells (SMC, n = 12), ventricular heart cells (VHC, n = 13),
      skeletal muscle cells (SKC, n = 13) or culture medium alone (control, n = 11).
      The ACE inhibitor group (n = 8) received enalapril (1.0 mg/kg per day), also
      beginning 3 weeks after cryoinjury. Five and 12 weeks after transplantation, left
      ventricle (LV) function was assessed in a Langendorff apparatus, and histologic
      and immunohistological evaluation of the LV scars was performed. RESULTS: At 5
      weeks, greater scar elastin content and better LV function was noted with cell
      transplantation or ACE inhibitor therapy compared with control rats (p < 0.05).
      Twelve weeks after transplantation, cell-transplanted rats still had greater
      elastin content and better LV function than control rats, although elastin
      content and LV function had declined in ACE inhibitor-treated animals to levels
      below those observed in control rats (p < 0.05). CONCLUSIONS: Transplantation of
      SMC, VHC, and SKC preserved ventricular function equivalent to the effects of an
      ACE inhibitor. Muscle cell transplantation, but not ACE inhibitor therapy,
      continues to be effective later after cryoinjury. No differences were detected
      between the muscle cells.

PMID- 14667645
TI  - Novel surgical system for reducing lung tissue and preventing air leaks.
AB  - PURPOSE: This study assessed the feasibility of using the VALR surgical system
      (Spiration Inc, Redmond, WA), limited by federal law to investigational use, for
      capturing and reducing a selected portion of affected lobes in patients
      undergoing lobectomy. DESCRIPTION: The tested system consists of a hand-held
      vacuum-regulated introducer loaded with a flexible, silicone sleeve. Targeted
      tissue is drawn into the introducer and the silicone sleeve is deployed and
      sutured in place. The end of the proximal sleeve includes a compression band for
      applying uniform radial pressure, suture ports, and silicone lugs lining the
      inner lumen for reinforcing sleeve position. EVALUATION: The system was effective
      in capturing 25% to 30% tissue of each lobe tested. Mean intraoperative test time
      was 8.5 minutes. The compression sleeve did not slip or dislodge after suturing,
      and no tissue damage or leaks were observed. CONCLUSIONS: It was feasible using
      vacuum to draw and isolate a portion of pulmonary tissue within a silicone
      sleeve. The system was intuitive to apply, easy to use, and produced effective
      reduction and sealing of tissue.

PMID- 14667647
TI  - Bronchial sleeve resection for posttransplant stricture.
AB  - Nonanastomotic bronchial stenosis is a rare complication of lung transplantation.
      We report a case of a bilateral lung transplant recipient who experienced
      recalcitrant stenosis of the bronchus intermedius. All attempts at conservative
      management failed, and the stricture was successfully treated by a parenchymal
      sparing segmental sleeve resection. Although rare, this is an important technique
      in the management of this difficult problem.

PMID- 14667648
TI  - Complex extralobar sequestration in a 24-year-old woman.
AB  - Extralobar sequestration is a congenital acquired disease more frequently
      observed after birth or during infancy. In half of the cases, it is associated
      with another malformation. In the following case we report the observation of a
      24-year-old female with right extralobar sequestration associated with a
      diaphragmatic hernia and containing gastric mucosa and a congenital cystic
      adenomatoid lung malformation. Such malformative lung tissue is known to
      potentially degenerate and justifies surgery even when patients are asymptomatic.

PMID- 14667649
TI  - Combined video-assisted thoracoscopic lung volume reduction surgery and lobectomy
      in a high-risk patient.
AB  - Nonsmall cell lung cancer often occurs in patients with severe emphysema.
      Lobectomy in these patients is often contraindicated due to extensive parenchymal
      destruction and subsequent pulmonary insufficiency. Video-assisted thoracoscopic
      lobectomy has been described as a less morbid procedure in high-risk patients.
      Lung volume reduction surgery has been shown to improve pulmonary function in
      selected patients with emphysema. We describe the successful combination of
      lobectomy and lung volume reduction surgery (LVRS) with a video-assisted
      thoracoscopic (VATS) approach in a high-risk patient with Stage I nonsmall cell
      lung cancer.

PMID- 14667650
TI  - Calcifying fibrous pseudotumor of the pleura: a rare location.
AB  - Calcifying fibrous pseudotumor is a rare lesion recently reported in the
      literature. We report a new case occurring in the pleura, which is an unusual
      location. The patient, a 38-year-old woman, had a left pleural mass revealed by
      chest roentgenograms. The tumor was resected by video-assisted thoracotomy. Only
      26 cases have been reported in the literature to date, but only 4 cases have been
      reported in the pleura. The pathogenesis is discussed but remains uncertain.
      Tumor resection appears to be the best option and the clinical course is benign.
      However, the number of cases to date is insufficient to establish therapeutic
      recommendations.

PMID- 14667651
TI  - Thymoliposarcoma.
AB  - Thymoliposarcoma is an exceedingly rare thymic neoplasm with only five reports in
      English literature to date. We report another patient, a 36-year-old male, who
      developed local recurrences 4-years after initial resection. The
      clinicopathologic features of the present and previously reports were compared
      with particular emphasis on their morphologic spectrum and differential
      diagnosis.

PMID- 14667652
TI  - Bronchial adenoma: an unusual cause of recurrent pneumonia in childhood.
AB  - Primary lung tumors are rare in childhood and often overlooked owing to the
      nonspecific presentation. We report the case of a 15-year-old boy with a 3-year
      history of recurrent pneumonia always involving the right lower lobe due to
      bronchial mucinous adenoma. After endoscopic removal the tumor recurred locally,
      necessitating open surgical resection of the tumor. In a child with localized
      recurrent pneumonia of uncertain pathogenesis, the differential diagnosis should
      include a primary lung tumor. Bronchial adenomas should not be removed
      endoscopically; patients must undergo open thoracotomy for surgical excision.

PMID- 14667653
TI  - Traumatic aortic transection in a child with an anomalous right subclavian
      artery.
AB  - We describe a child who presented with a traumatic aortic transection in the
      setting of anomalous origin of the right subclavian artery. This abnormal arch
      anatomy may influence the diagnosis, anatomic location, and technique of surgical
      repair of the injury.

PMID- 14667654
TI  - Restrictive interatrial communication in hypoplastic left heart syndrome after
      modified Fontan repair.
AB  - The occurrence of pulmonary venous obstruction after total cavopulmonary
      connection with intraatrial lateral tunnel is a rare occurrence. We present two
      cases of hypoplastic left heart syndrome with restrictive interatrial
      communication presenting late after this type of modified Fontan repair. This
      occurred even after complete excision of the atrial septum at the time of Stage 1
      Norwood in both cases. A novel approach to this problem of resecting the roof of
      the coronary sinus was utilized to enlarge the interatrial communication.

PMID- 14667655
TI  - Atresia of coronary sinus ostium with retrograde drainage via persistent left
      superior vena cava.
AB  - Atesia of the coronary sinus ostium (ACSO) with retrograde drainage of cardiac
      veins via the left superior vena cava (LSVC) is a very rare abnormality. This
      condition is usually asymptomatic during life and a majority of the cases were
      reported as incidental postmortem findings. If there is retrograde venous
      drainage via persistent LSVC, this communication cannot be ligated irrespective
      of its size or the presence of a communicating vein because of resultant cardiac
      congestion and edema. We report herein a 9-month-old Chinese female who underwent
      repair of a perimembranous ventricular septal defect, patent ductus arteriosus
      and secundum atrial septal defect. During the operation, ligation of LSVC
      resulted in myocardial congestion and distension of the heart. The release of
      ligature decompressed the heart immediately.

PMID- 14667656
TI  - Palliative open heart surgery in an infant with factor VII deficiency.
AB  - An infant with factor VII deficiency underwent palliative open heart surgery for
      pulmonary atresia with an intact ventricular septum. No references had been found
      on the management of this rare coagulation disorder in infantile cardiac surgery.
      We describe the peri- and postoperative management with a replacement therapy
      including a recombinant factor VIIa concentrate. We conclude that an appropriate
      replacement therapy is needed to control bleeding during open heart surgery with
      factor VII deficiency.

PMID- 14667657
TI  - Use of recombinant factor VIIa as a rescue treatment for intractable bleeding
      following repeat aortic arch repair.
AB  - Hemorrhage, refractory to aggressive conventional therapy, at a rate of 16 L/hr
      following separation from cardiopulmonary bypass for aortic arch repair, was
      controlled with a dose of 90 microg/kg of recombinant factor VIIa, repeated once
      after 2 hours.

PMID- 14667658
TI  - Cavernous hemangioma of the tricuspid valve: minimally invasive surgical
      resection.
AB  - Cardiac hemangioma is a rare, benign vascular tumor, occurring with an incidence
      of 1% to 2% of all detected benign heart neoplasms. Hemangioma of the tricuspid
      valve has never been previously reported. We describe the successful excision of
      this tumor through a right anterolateral mini-thoracotomy in a 49-year-old woman.
      Competency of the valve was confirmed intraoperatively and at discharge by
      transesophageal echocardiography.

PMID- 14667659
TI  - A modified valve-on-valve approach for aortic root replacement.
AB  - We describe an alternative surgical technique for aortic root replacement in a
      patient whose aortic valve was previously replaced with a bioprosthesis. It
      consists of resecting the leaflets of the original bioprosthesis in situ,
      amputating the struts, and suturing the skirt of a composite graft on the
      preserved annulus of the original bioprosthesis. Coronary circulation is
      reconstructed according to the Cabrol modification. This approach simplifies and
      shortens the procedure of aortic root replacement, minimizing the potential
      hazard of hemorrhage from the proximal suture line in these cases.

PMID- 14667660
TI  - Resolved hypersensitivity myocarditis after ventricular circulatory assist.
AB  - Hypersensitivity myocarditis is known to be a cardiac manifestation of a delayed
      type hypersensitivity response caused by drug treatment. In heart transplantation
      candidates the incidence is elevated. We report the case of a patient with end
      stage heart failure who underwent implantation of a left ventricular assist
      device as a bridge to transplantation. The histologic investigation of the left
      ventricular specimen obtained during device implantation revealed the diagnosis
      of a hypersensitivity myocarditis. Ten months later this lesion showed complete
      reversibility within specimens of the explanted heart, maybe as a result of the
      termination of inotropic therapy after implantation of the left ventricular
      assist device.

PMID- 14667661
TI  - New strategy for treatment of MRSA mediastinitis: one-stage procedure for omental
      transposition and closed irrigation.
AB  - Mediastinitis due to methicillin-resistant Staphylococcus aureus is a devastating
      potential complication of cardiac surgery. We treated 4 patients with this
      condition using a new technique. First we performed an early radical removal of
      infected tissue and omental transposition with direct primary closure of the
      sternum and closed continuous irrigation with saline/vancomycin hydrochloride;
      that was followed by an administration of intravenous antibiotics. We obtained
      good clinical results, which are reported herein along with the clinical courses.

PMID- 14667662
TI  - Thymic intracapsular hematoma caused by blunt chest trauma.

PMID- 14667663
TI  - Images of the human coronary sinus ostium obtained from isolated working hearts.

PMID- 14667664
TI  - Special considerations on the implantation technique for the MicroMed-DeBakey
      ventricular assist device axial pump.
AB  - Implantable continuous flow axial pumps were introduced to clinical settings in
      November 1998 with the MicroMed-DeBakey ventricular assist device. Axial pumps
      continuously unload the failing left ventricle and accurate positioning of the
      inflow cannula prevents substantial reductions in pump flow. Considerations on
      the implantation technique are made to minimize surgical trauma, to prevent
      ventricular collapse, to optimize inflow conditions (flow increased from 4.3 +/-
      0.6 to 6.7 +/- 0.3 L/min), and to facilitate the subsequent transplantation.

PMID- 14667665
TI  - New approach in treatment of acute cardiogenic shock requiring mechanical
      circulatory support.
AB  - In 12 patients with acute cardiogenic shock who required mechanical circulatory
      support a short-term Abiomed BVS 5000 extracorporeal assist device was implanted
      using the inflow and outflow cannulas of the BerlinHeart extracorporeal assist
      device. In 7 patients suitable for long-term support the Abiomed pumps were later
      exchanged for BerlinHeart pumps. This approach avoids the risks associated with
      repeat sternotomy and use of cardiopulmonary bypass and decreases the total costs
      of patient care.

PMID- 14667666
TI  - Totally normothermic aortic arch replacement without circulatory arrest.
AB  - The authors propose a new strategy of normothermic perfusion for replacement of
      the aortic arch to avoid the complications of profound hypothermic circulatory
      arrest. Six patients underwent complete replacement of the aortic arch under
      normothermia using two pumps for the body (one for the brain and the
      thoracoabdominal aortic branches) and one for the heart. The surgical procedure
      was performed with no time limit. There were no operative or late deaths. No
      patients had neurologic deficit and all were rapidly extubated with uneventful
      postoperative courses. The method preserves autoregulation of cerebral blood flow
      and maintains body perfusion without high vascular resistances.

PMID- 14667667
TI  - A technique for evaluating competitive flow for intraoperative decision making in
      coronary artery surgery.
AB  - The effect of native coronary competitive flow on the patency of arterial and
      saphenous vein grafts is controversial. We use a simple intraoperative technique
      to evaluate competitive flow that allows us to make informed intraoperative
      decisions regarding anastomotic quality, vessel runoff, and competing native
      coronary blood flow.

PMID- 14667668
TI  - Heparin-induced thrombocytopenia and cardiac surgery.
AB  - Unfractionated heparin given during cardiopulmonary bypass is remarkably
      immunogenic, as 25% to 50% of postcardiac surgery patients develop heparin
      dependent antibodies during the next 5 to 10 days. Sometimes, these antibodies
      strongly activate platelets and coagulation, thereby causing the prothrombotic
      disorder, heparin-induced thrombocytopenia. The risk of heparin-induced
      thrombocytopenia is 1% to 3% if unfractionated heparin is continued beyond the
      first postoperative week. When cardiac surgery is urgently needed for a patient
      with acute or subacute heparin-induced thrombocytopenia, options include an
      alternative anticoagulant (bivalirudin, lepirudin, or danaparoid) or combining
      unfractionated heparin with a platelet antagonist (epoprostenol or tirofiban). As
      heparin-induced thrombocytopenia antibodies are transient, unfractionated heparin
      alone is appropriate in a patient with previous heparin-induced thrombocytopenia
      whose antibodies have disappeared.

PMID- 14667669
TI  - Statins in coronary bypass surgery: rationale and clinical use.
AB  - Statin therapy prevents the first occurrence and recurrence of coronary events
      and reduces cardiovascular and general mortality in patients with coronary artery
      disease. These compounds modulate a variety of processes involved in the
      pathophysiology of arteriosclerosis and vascular graft disease by lipid-dependent
      and lipid-independent (pleiotropic) mechanisms. As a result, statins produce
      angiographic and clinical benefits in patients undergoing coronary bypass
      surgery. We review the present knowledge about the effects of statins on this
      pathologic condition and the evidence supporting an early treatment initiation.

PMID- 14667670
TI  - Leg wound infection after coronary artery bypass grafting: a meta-analysis
      comparing minimally invasive versus conventional vein harvesting.
AB  - The great saphenous vein remains the most commonly harvested conduit for
      revascularization in coronary artery bypass grafting (CABG). Our aim is to
      compare minimally invasive vein harvest techniques to conventional vein harvest
      with regards to leg wound infection rates. A meta-analysis of identified
      randomized controlled trials, reporting a comparison between the two techniques
      published between 1965 and 2002, was undertaken. The outcome of interest was leg
      wound infection. Fourteen randomized studies were identified and included in the
      meta-analysis. Our study revealed that wound infection was significantly lower in
      the minimally invasive vein harvest group (odds ratio 0.22 with 95% confidence
      intervals of 0.14 to 0.34). Our study suggests that using minimally invasive
      techniques might reduce leg wound infection rate following great saphenous vein
      harvesting for CABG. Further research is required to evaluate the potential
      benefits of minimally invasive vein harvesting techniques on the cost of
      postoperative care and quality of the harvested vein.

PMID- 14667671
TI  - The evolution of cardiovascular surgery in China.
AB  - The history of the development of cardiovascular surgery in China was little
      known to the West not only because the majority of the earlier reports were
      published almost exclusively in the Chinese language but also because China was
      essentially closed to the West before the 1980s. We present here an account of
      how some Chinese surgeons struggled to establish a new specialty in a country
      that makes up more than one fifth of the world population.

PMID- 14667672
TI  - The STS future planning conference for adult cardiac surgery.

PMID- 14667673
TI  - Usefulness of pulsatile bidirectional cavopulmonary shunt in high-risk Fontan
      patients.

PMID- 14667675
TI  - Expected freedom from structural degeneration and patient outgrowth for the
      bovine jugular vein conduit: is it possible to calculate a safe rate for
      children?

PMID- 14667677
TI  - Assessment of different procedures for surgical left atrial appendage exclusion.

PMID- 14667678
TI  - Revisiting Dr Carlos Duran's work.

PMID- 14667681
TI  - Gibbon and his Heart-Lung Machine: 50 Years and Beyond. Philadelphia,
      Pennsylvania, USA. May 2, 2003.

PMID- 14667682
TI  - John Gibbon and the heart-lung machine: a personal encounter and his import for
      cardiovascular surgery.

PMID- 14667683
TI  - Reminiscences of John H. Gibbon, Jr, MD.

PMID- 14667684
TI  - Retrospective on Dr Gibbon and his heart-lung machine.

PMID- 14667685
TI  - Remembering John H. Gibbon, Jr, MD.

PMID- 14667686
TI  - Recollections on Dr John H. Gibbon, Jr.

PMID- 14667687
TI  - Laboratory work preceding the first clinical application of cardiopulmonary
      bypass.

PMID- 14667688
TI  - The evolution of the helical reservoir pump-oxygenator system at the University
      of Minnesota.
AB  - Open heart surgery was not possible before the early 1950s. The development of
      controlled cross-circulation at the University of Minnesota in 1953 was a major
      contributing factor toward operating safely on the interior of the heart. Cross
      circulation required connecting a donor's arterial and venous blood vessels to
      those of a smaller recipient whose heart could then be opened for corrective
      surgery. At that time no mechanical system was available to serve the role of the
      donor. The need to replace the donor was recognized. The author describes his
      experience with the development of the helical reservoir bubble oxygenator, which
      replaced the donor in cross-circulation supported open heart surgery. Other
      sidelights of the author's experience during the early days of open heart surgery
      at the University of Minnesota Department of Surgery are also recounted.

PMID- 14667689
TI  - The development of the modern oxygenator.
AB  - From 1953 when Gibbon first successfully supported a patient with extracorporeal
      circulation to about 1980 many different types of oxygenators were developed.
      Since their introduction in the early 1980s, microporous hollow fiber oxygenators
      with blood flow outside the fiber have become the dominant type of oxygenator in
      use. Their success has been due to both the ability to specify the required
      properties for a good oxygenator and the application of modern design tools,
      especially computational fluid dynamics, to the design process. The result has
      been the availability of many oxygenators from different manufacturers that
      differ to some extent in their performance but all of which provide adequate
      performance for successful and safe clinical use.

PMID- 14667690
TI  - Advances in the heart-lung machine after John and Mary Gibbon.

PMID- 14667691
TI  - The development and use of extracorporeal membrane oxygenation in neonates.
AB  - Extracorporeal membrane oxygenation (ECMO) is the utilization of a modified heart
      lung machine to provide temporary support for patients with severe respiratory or
      cardiac failure. In contrast to patients managed with traditional cardiopulmonary
      bypass, patients on ECMO undergo cannulation of relatively accessible blood
      vessels, are maintained at normal body temperature, and only require partial
      anticoagulation with heparin. Although first developed for use in adults, ECMO
      has been most successful in the treatment of newborn infants with life
      threatening pulmonary failure. Since 1974, over 17,000 infants have received ECMO
      with a 78% survival rate. There is a 15%-20% incidence of neurodevelopmental
      disabilities among ECMO survivors.

PMID- 14667692
TI  - Mechanical heart valves: 50 years of evolution.
AB  - The past 50 years have witnessed remarkable progress in the development of safe,
      hemodynamically favorable mechanical heart valves. Starr-Edwards aortic and
      mitral ball valves introduced in the mid-1960s, continue to be used successfully
      worldwide. More than 100,000 Omniscience and Omnicarbon tilting-disc valves have
      been implanted since 1978 with essentially no mechanical failure; similar results
      have been obtained with more than 300,000 Hall-Kaster and Medtronic-Hall tilting
      disc valves over the past 25 years. Pyrolytic carbon, originally used to
      encapsulate nuclear fuel rods, has been adapted for the fabrication of discs,
      leaflets and the housings for more than 2 million mechanical valves. The St. Jude
      bileaflet valves, totally fabricated from pyrolytic carbon, have remained
      virtually unchanged in design since their introduction in 1977. More than 1.3
      million of these valves have been implanted worldwide with virtually no reported
      failures of the carbon leaflets or housings. Similarly, pyrolytic carbon
      bileaflet Carbomedics valves have been implanted in more than 500,000 patients
      since 1986. Now, 50 years after Dr Gibbon's seminal achievement, patients with
      debilitating valve disease can have elective valve replacement (mechanical or
      tissue) with an operative mortality approaching 1% to 2% and a low lifetime
      complication rate.

PMID- 14667693
TI  - Advances in the treatment of coronary artery disease.
AB  - Initial pioneering efforts of direct coronary artery bypass were all performed on
      a beating heart. Although originally introduced into cardiac surgery for the
      repair of intracardiac defects, the ability of John Gibbon's heart-lung machine
      to create a motionless, bloodless operative field catalyzed coronary artery
      bypass surgery. During the ensuing decades tens of millions of patients benefited
      from coronary revascularization on cardiopulmonary bypass. As we celebrate the
      50th anniversary of the invention of the heart-lung machine the landscape of
      interventional treatment of coronary artery disease has shifted dramatically.
      Although instrumental in the genesis of the field of coronary revascularization,
      the role of the heart-lung machine has now diminished. Two thirds of all coronary
      revascularization is now performed by percutaneous approaches and one fourth of
      all coronary artery bypass grafting procedures are performed without the heart
      lung machine. However owing to the complexity of patients now requiring
      revascularization as well as recently introduced incremental improvements to
      cardiopulmonary bypass including coated, low prime circuits, closed integrated
      systems, and pharmacologic adjuncts Gibbon's heart-lung machine will continue to
      play an integral role in this field.

PMID- 14667694
TI  - The emerging role of pharmacogenomics in the treatment of patients with heart
      failure.

PMID- 14667695
TI  - Surgical treatment of congestive heart failure: evolving options.

PMID- 14667696
TI  - Knowledge, expectations, and inductive reasoning within conceptual hierarchies.
AB  - Previous research (e.g. Cognition 64 (1997) 73) suggests that the privileged
      level for inductive inference in a folk biological conceptual hierarchy does not
      correspond to the "basic" level (i.e. the level at which concepts are both
      informative and distinct). To further explore inductive inference within
      conceptual hierarchies, we examine relations between knowledge of concepts at
      different hierarchical levels, expectations about conceptual coherence, and
      inductive inference. In Experiments 1 and 2, 5- and 8-year-olds and adults listed
      features of living kind (Experiments 1 and 2) and artifact (Experiment 2)
      concepts at different hierarchical levels (e.g. plant, tree, oak, desert oak),
      and also rated the strength of generalizations to the same concepts. For living
      kinds, the level that showed a relative advantage on these two tasks differed;
      the greatest increase in features listed tended to occur at the life-form level
      (e.g. tree), whereas the greatest increase in inductive strength tended to occur
      at the folk-generic level (e.g. oak). Knowledge and induction also showed
      different developmental trajectories. For artifact concepts, the levels at which
      the greatest gains in knowledge and induction occurred were more varied, and
      corresponded more closely across tasks. In Experiment 3, adults reported beliefs
      about within-category similarity for concepts at different levels of animal,
      plant and artifact hierarchies, and rated inductive strength as before. For
      living kind concepts, expectations about category coherence predicted patterns of
      inductions; knowledge did not. For artifact concepts, both knowledge and
      expectations predicted patterns of induction. Results suggest that beliefs about
      conceptual coherence play an important role in guiding inductive inference, that
      this role may be largely independent of specific knowledge of concepts, and that
      such beliefs are especially important in reasoning about living kinds.

PMID- 14667697
TI  - Antecedent frequency effects during the processing of pronouns.
AB  - An eye-movement reading experiment investigated whether the ease with which
      pronouns are processed is affected by the lexical frequency of their antecedent.
      Reading times following pronouns with infrequent antecedents were faster than
      following pronouns with frequent antecedents. We argue that this is consistent
      with a saliency account, according to which infrequent antecedents are more
      salient than frequent antecedents. The results are not predicted by accounts
      which claim that readers access all or part of the lexical properties of the
      antecedent during the processing of pronouns.

PMID- 14667698
TI  - Priming infants to attend to color and pattern information in an individuation
      task.
AB  - Wilcox (Cognition 72 (1999) 125) reported that infants are more sensitive to form
      than surface features when individuating objects in occlusion events: it is not
      until 7.5 months that infants spontaneously use pattern information, and 11.5
      months that they spontaneously use color information, as the basis for object
      individuation. The present research assessed the extent to which infants'
      sensitivity to surface features could be increased under more supportive
      conditions. More specifically, we examined whether younger infants could be
      primed to draw on color and pattern features in an individuation task if they
      were first shown the functional value of attending to color and pattern
      information (i.e. the color or the pattern of an object predicted the function it
      would engage in). Five experiments were conducted with infants 4.5 to 9.5 months
      of age. The main findings were that 9.5- and 7.5-month-olds could be primed to
      use color information, and 5.5- and 4.5-month-olds could be primed to attend to
      pattern information, after viewing the function events. The results are discussed
      in terms of the kinds of experiences that can lead to increased sensitivity to
      surface features and the mechanisms that support feature priming in young
      infants.

PMID- 14667699
TI  - A mechanism of implicit lexicalized phonological recoding used concurrently with
      underdeveloped explicit letter-sound skills in both precocious and normal reading
      development.
AB  - These are findings of theoretical interest from: (i) follow-up of a case study of
      a precocious reader; and (ii) normally developing readers who served as
      comparison groups. The precocious reader was first reported when 2-3 years of age
      (Cognition 74 (2000) 177). From 3 to 7 years of age her precocious reading
      development continued, her word reading accuracy increasing from the 8- to the 16
      year-level, although her phonemic awareness skills remained underdeveloped
      relative to word reading. Nonword reading continued to develop rapidly. Her word
      reading, however, was more than phonological recoding. At 5 years of age, in
      comparison with reading-level matched normal 11-year-olds she exhibited strong
      effects of semantic characteristics of words and evidence of well-specified
      lexical orthographic representations. In common with normal comparison 11-year
      olds, who had not received instruction in explicit phonics, her explicit letter
      sound skills were underdeveloped but she possessed high speed and accuracy in
      nonword reading, a result most theories of the acquisition of reading fail to
      explain. Her responses to irregularly spelt nonwords indicated higher proficiency
      than the 11-year-olds in acquiring lexical orthographic representations not
      predictable from prior phonological recoding knowledge. It is considered that
      this proficiency contributes to an explanation of her precocious reading
      development. A mechanism of implicit lexicalized phonological recoding is
      involved which explains the dissociation of skills in both the precocious reader
      and normally developing readers.

PMID- 14667700
TI  - A new synthesis of the oligosaccharide domain of acarbose.
AB  - Synthesis of the oligosaccharide domain of acarbose was reinvestigated and was
      optimally performed using a maltosidic acceptor, already bearing a alpha-D-Glc-(1
      ->4)-D-Glc bond, and a new D-fucopyranosyl donor. The crucial glycosylation step
      was improved by varying three different parameters and notably by focusing on the
      C-4 protecting group of the fucosyl residue, solvent and promoter. The resulting
      trisaccharide was further transformed into an electrophilic species in order to
      open further derivatization perspectives for designing new acarbose analogues.
      Substitution reactions were efficiently carried out with azide and thiocyanate
      anions. Two other potentially interesting trisaccharidic compounds were also
      synthesized, i.e. the C-4III amine and the corresponding isothiocyanate.

PMID- 14667701
TI  - Studies on the endogenous L-selectin ligands: systematic and highly efficient
      total synthetic routes to lactamized-sialyl 6-O-sulfo Lewis X and other novel
      gangliosides containing lactamized neuraminic acid.
AB  - Systematic syntheses of lactamized neuraminic acid-containing gangliosides GM4,
      sulfated sialylparagloboside, and sulfated/nonsulfated sialyl Lewis X are
      described. The highly efficient, one-step lactamization of neuraminic acid was
      accomplished by treatment of the N-deacetylated sialic acid (neuraminic acid)
      containing gangliosides with HBTU and HOBt in DMF at 65 degrees C. Both the
      lactamized neuraminic acid residue and the sulfate group at O-6 of the GlcNAc
      residue were found to be involved in the antigenic determinant defined by G159
      monoclonal antibody, while the fucose residue may not be critical for the
      recognition by G159 mAb.

PMID- 14667702
TI  - Synthesis of two heptasaccharide analogues of the lentinan repeating unit.
AB  - beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)
      [beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->6)]-beta-D-Glcp (18) and the allyl
      glycoside of beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp-(1-->3)-beta-D
      Glcp-(1-->3)-beta-D-Glcp-(1-->3)[-beta-D-Glcp-(1-->6)]-alpha-D-Glcp (29) were
      synthesized as the analogues of the lentinan repeating heptaose by building the
      pentasaccharide backbones first, followed by attaching the side chains. 4,6-O
      benzylidenated mono-13 or disaccharide 8 were used as the acceptor to ensure the
      beta linkage in the synthesis of 18, while 4,6-O-benzylidenated disaccharides 21
      and 23 were used as the donor and acceptor, respectively, to ensure the beta
      linkage in the synthesis of 29.

PMID- 14667703
TI  - Utilization of nosylepimines of 1,6-anhydro-beta-D-hexopyranoses for the
      preparation of halogenated aminosaccharides.
AB  - The aziridine ring cleavage of N-nosylepimines 3 and 7 having D-allo and D-manno
      configurations with halides led regioselectively to N-o-nitrobenzenesulfonylated
      2-halo-3-amino- and 3-halo-2-amino-2,3-dideoxy derivatives of 1,6-anhydro-beta-D
      glucopyranose 8-14 in 59-81% yields. Removal of o-nitrobenzenesulfonyl protecting
      group with benzenethiol afforded aminosaccharides, which were converted into more
      stable hydrochlorides 15-18.

PMID- 14667704
TI  - The effect of (1-->3)-beta-D-glucans, carboxymethylglucan and schizophyllan on
      human leukocytes in vitro.
AB  - (1-->3)-beta-D-glucans are known as potent inductors of humoral and cell-mediated
      immunity in humans and animals. (1-->3)-beta-D-glucans isolated from various
      sources differ in their chemical structure and physical parameters and
      consequently in their immunomodulatory potential. In this study the
      immunomodulatory activity of two (1-->3)-beta-D-glucans schizophyllan (SPG) and
      carboxymethylglucan (CMG) was determined and compared on human blood leukocytes
      in vitro. Both SPG and CMG activated blood phagocytes and lymphocytes as
      demonstrated by increased whole blood production of reactive oxygen species, by
      increased production of pro-inflammatory cytokines IL-6, IL-8, and TNF-alpha, by
      increased surface expression of CD69 on lymphocytes, and by altered expression of
      CD11b and CD62L on polymorphonuclear leukocytes and monocytes. SPG demonstrated a
      significantly higher potential to stimulate blood phagocytes and production of
      selected pro-inflammatory cytokines than CMG. The higher potency of SPG to
      stimulate human blood phagocytes in vitro could be caused by factors such as
      higher branching frequencies or neutral polymer charge of SPG or different
      conformation in solution if compared with CMG.

PMID- 14667705
TI  - cDNA cloning of an alginate lyase from abalone, Haliotis discus hannai.
AB  - An alginate lyase, termed HdAly in the present paper, was isolated from the
      hepatopancreas of abalone, Haliotis discus hannai, by ammonium sulfate
      fractionation, followed by TOYOPEARL CM-650M column chromatography. Enzymatic
      properties of HdAly were similar to those of previously reported Haliotis and
      Turbo poly(M) lyases, e.g., it preferentially degraded a poly(beta-D-mannuronate)
      rich substrate with an optimal pH and temperature at pH 8.0 and 45 degrees C,
      respectively. In order to determine the primary structure of abalone lyase that
      is still poorly understood, cDNAs for HdAly were cloned by PCR from the abalone
      hepatopancreas cDNA library and sequenced. From the nucleotide sequences of the
      cDNAs, the sequence of 909 bp in total was determined, and the amino acid
      sequence of 273 residues was deduced from the translational region of 822 bp
      locating at nucleotide positions 27-848. The N-terminal region of 16 residues,
      except for the initiation Met in the deduced sequence, was regarded as the signal
      peptide since it was absent in the HdAly protein and showed high similarity to
      the consensus sequence for signal peptides of eukaryote secretary proteins. This
      suggests that HdAly is initially produced as a precursor possessing the signal
      peptide in hepatopancreatic cells and then secreted into digestive tract as the
      mature form. Thus, the mature HdAly was regarded to consist of 256 residues with
      the calculated molecular mass of 28895.5 Da. The amino acid sequence of HdAly
      showed 85 and 28% identity to those of Turbo cornutus alginate lyase SP2 and the
      C-terminal region of Chlorella virus lyase-like protein CL2, respectively, while
      it showed no significant identity to those of any bacterial alginate lyases. In
      order to provide the basis for the structure-function studies and various
      applications of the abalone lyase, a bacterial expression system was constructed
      by means of the HdAly-cDNA and pET-3a expression plasmid. Although the active
      recombinant HdAly was hardly produced at a cultivation temperature 37 degrees C
      in Escherichia coli BL21 (DE3), a small amount of soluble and active enzyme could
      be produced when the temperature was lowered to 19 degrees C.

PMID- 14667706
TI  - An isocratic separation of underivatized gentamicin components, 1H NMR assignment
      and protonation pattern.
AB  - A simple method for the separation of the major components of commercial
      gentamicin sulfate (C-1, C-1a, C-2, C-2a) by high-performance liquid
      chromatography (HPLC) on an analytical and a semipreparative scale was developed.
      The method utilized ion-pair reversed-phase chromatography, isocratic elution
      with an aqueous solution containing 9% trifluoroacetic acid and 2.5% acetonitrile
      as the mobile phase at a flow rate of 2 and 9 mL/min for analytical and
      semipreparative columns, respectively. Detection was carried out at 213 nm
      without derivatization. The protonation pattern of the separated gentamicins was
      determined by potentiometry and 15N and 1H NMR. The full proton NMR assignment
      for gentamicin C-1 was obtained through the use of 1H 1D and 2D 1H-1H COSY
      measurements.

PMID- 14667707
TI  - Chain conformation of sulfated derivatives of beta-glucan from sclerotia of
      Pleurotus tuber-regium.
AB  - Six water-insoluble (1-->3)-beta-D-glucan fractions TM8-1 to TM8-6 with weight
      average molecular mass Mw ranging from 5.76 to 77.4x10(4) obtained from the
      sclerotia of Pleurotus tuber-regium were sulfated to produce the water-soluble
      fractions S-TM8-1 to S-TM8-6 with Mw from 6.0 to 64.8x10(4). The degree of
      substitution (DS) of S-TM8 fractions was analyzed by elemental analysis (EA) to
      be 1.14-1.74. The 13C NMR results indicated that the C-6 was fully substituted,
      and C-2, C-4 were partially substituted by the sulfo-groups. The Mw and the
      intrinsic viscosity [eta] of the S-TM8 fractions were measured, respectively, by
      size-exclusion chromatography combined with laser light scattering (SEC-LLS), LLS
      and viscometry in phosphate buffer solution (PBS) at 37 degrees C. The
      dependences of [eta] and radius of gyration <s2>z(1/2) on Mw for the S-TM8
      samples were found to be [eta]=1.89x10(-2) Mw(0.70) (cm3/g) and
      <s2>z(1/2)=1.12x10(-4) Mw(0.81) (nm) in the Mw range tested. Based on current
      theories for a wormlike chain model, the molar mass per unit contour length ML
      and persistence length q of the S-TM8 were calculated to be 990 nm(-1) and 8.5
      nm, respectively. The relatively higher q value suggested a more expanded
      flexible chain of S-TM8 in PBS. The water-solubility and relatively expanded
      chain conformation of the STM8 fractions were considered to be significant to
      their antiviral activity.

PMID- 14667708
TI  - Acid hydrolysis of native and annealed starches and branch-structure of their
      Naegeli dextrins.
AB  - Eight commercial starches, including common corn, waxy corn, wheat, tapioca,
      potato, Hylon V, Hylon VII, and mung bean starch, were annealed by a multiple
      step process, and their gelatinization characteristics were determined. Annealed
      starches had higher gelatinization temperatures, reduced gelatinization ranges,
      and increased gelatinization enthalpies than their native starches. The annealed
      starches with the highest gelatinization enthalpies were subjected to acid
      hydrolysis with 15.3% H2SO4, and Naegeli dextrins were prepared after 10 days'
      hydrolysis. Annealing increased the acid susceptibility of native starches in the
      first (rapid) and the second (slow) phases with potato starch showing the
      greatest and high amylose starches showing the least changes. Starches with a
      larger shift in onset gelatinization temperature also displayed a greater percent
      hydrolysis. The increase in susceptibility to acid hydrolysis was proposed to
      result from defective and porous structures that resulted after annealing.
      Although annealing perfected the crystalline structure, it also produced void
      space, which led to porous structures and possible starch granule defects. The
      molecular size distribution and chain length distribution of Naegeli dextrins of
      annealed and native starches were analyzed. The reorganization of the starch
      molecule during annealing occurred mainly within the crystalline lamellae.
      Imperfect double helices in the crystalline lamellae improved after annealing,
      and the branch linkages at the imperfect double helices became protected by the
      improved crystalline structure. Therefore, more long chains were observed in the
      Naegeli dextrins of annealed starches than in native starches.

PMID- 14667709
TI  - Volumetric behaviour of maltose-water, maltose-glycerol and starch-sorbitol-water
      systems mixtures in relation to structural relaxation.
AB  - The densities of amorphous maltose-water, maltose-glycerol and starch-sorbitol
      water mixtures were measured using a vibrating-tube density meter and pycnometry.
      The volumetric change on mixing was investigated through the calculation of the
      quantity DeltaV/V, the difference between (experimental) volume of the mixture
      and the linear composition weighted pure constituent volumes (ideal mixing). For
      all of the systems studied the quantity DeltaV/V was negative and approached a
      minimum of -0.03 and -0.015 at mass fractions of maltose in the region of 0.75
      and 0.85 for the maltose-water and maltose-glycerol mixtures, respectively.
      Results are discussed in the context of volume change due to structural
      relaxation of vitreous materials and related to the phenomenon of
      antiplasticisation.

PMID- 14667710
TI  - Acetan:glucomannan interactions--a molecular modeling study.
AB  - X-ray fiber diffraction patterns from deacylated acetan and glucomannan (konjac
      mannan) blends are diagnostic of good orientation and modest polycrystallinity.
      The meridional reflection on the sixth layer line suggests that the binary
      complex is a 6-fold helix of pitch 55.4 A. A molecular modeling study
      incorporating this information reveals that a double helix in which one strand is
      acetan and the other glucomannan is stereochemically feasible. While the backbone
      and side groups are sufficiently flexible to allow the chains to associate with
      the same or opposite polarity, the parallel model is superior in terms of unit
      cell packing. The results are compatible with the observed synergy; namely the
      weak gelation behavior of the complex. The molecular model can be generalized for
      the binary system when acetan is replaced by xanthan or glucomannan by
      galactomannan.

PMID- 14667711
TI  - Consequences of rigidity and conformational locking in a 4,4-dimethyl-1,3
      dioxolane ring system during protection of internal diol.
AB  - The presence of an isopropylidene ketal protection of an internal diol in 3,4-O
      isopropylidene-D-arabino-1-C-phenyl hexanone locks it in a conformation that
      prevents its cyclization to a pyranose ring.

PMID- 14667712
TI  - Phase-variation of the truncated lipo-oligosaccharide of Neisseria meningitidis
      NMB phosphoglucomutase isogenic mutant NMB-R6.
AB  - The detection of antibodies specific to meningococcal lipo-oligosaccharides
      (LOSs; outer-core-->inner-core-->lipid A) in sera of patients convalescent from
      meningococcal infection suggests the potential use of LOS as a vaccine to combat
      pathogenic Neisseria spp. Removal of the outer-core region, which expresses
      glycans homologous to human blood-group antigens, is a required first-step in
      order to avoid undesirable immunological reactions following vaccination. To this
      end, we describe here the structural makeup of the LOS produced by serogroup B N.
      meningitidis NMB isogenic phosphoglucomutase (Pgm) mutant (NMB-R6). The dominant
      LOS types produced by NMB-R6 expressed a deep-truncated inner-core region, GlcNAc
      (1-->2)-LDHepII-(1-->3)-LDHepI-(1-->5)-[Kdo-2-->4]-Kdo-->lipid A, with one PEA
      unit attached at either O-6 or O-7 of LDHepII, or with two simultaneously PEA
      moieties attached at O-3 and O-6 or O-3 and O-7 of the same unit. Unexpectedly,
      this mutation did not completely deactivate the production of Glc, as some LOS
      molecules were observed to carry Glc at O-4 of LDHepI and at O-3 of LDHepII. A
      glycoconjugate vaccine comprised of NMB-R6 LOSs is currently being evaluated in
      our laboratory.

PMID- 14667713
TI  - Metal ion interactions with sugars. The crystal structure and FT-IR study of the
      NdCl3-ribose complex.
AB  - The single-crystal structure of neodymium chloride-ribopyranose pentahydrate,
      NdCl3.C5H10O5.5H2O was determined to have Mr=490.80, a=9.138(11), b=8.830(10),
      c=9.811(11) A, beta=94.087(18) degrees, V=789.7(16) A3, P2(1), Z=2, mu=0.71073 A
      and R=0.0198 for 2075 observed reflections. The ligand of the title complex was
      observed in a disordered state and two molecular configurations of
      NdCl3.C5H10O5.5H2O were found in the single crystal as a pair of isomers. Both
      ligand moieties of the two molecules are ribopyranose forms, providing three
      hydroxyl groups in ax-eq-ax orientation for coordination. One ligand of the pair
      of isomers is beta-D-ribopyranose in the 1C4 conformation, and the other is alpha
      D-ribopyranose in the 4C1 conformation. The Nd3+ ion is nine-coordinated with
      five Nd-O bonds from water molecules, three Nd-O bonds from hydroxyl groups of
      the ribopyranose and one Nd-Cl bond from chloride ion. The hydroxyl groups, water
      molecules, 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 accordance with those of X-ray spectroscopy.

PMID- 14667714
TI  - Viscosity B-coefficients and activation parameters for viscous flow of a solution
      of heptanedioic acid in aqueous sucrose solution.
AB  - Viscosity and density data for the system of heptanedioic acid dissolved in
      aqueous sucrose solution at temperature range from 288.15 to 313.15 K have been
      measured. The viscosity B-coefficients for heptanedioic acid in aqueous sucrose
      solution has been calculated. The effect of temperature and sucrose concentration
      on the B-coefficients is discussed. On the basis of the Feakins equation, the
      activation parameters (Deltamu3++, DeltaH3++, DeltaS3++, DeltaG12(0)++,
      DeltaH12(0)++ and DeltaS12(0)++) for viscous flow of the solution have been
      evaluated, together with the Gibbs energy of transfer for the solute from the
      ground state solvent to the hypothetical viscous transition state solvent
      (DeltaG3++(1-1')). The effect of sucrose concentration and temperature on the
      activation parameters has been discussed.

PMID- 14667715
TI  - Regional and global contamination by POPs. Editorial.

PMID- 14667716
TI  - Primary sources of selected POPs: regional and global scale emission inventories.
AB  - During the last decade, a number of studies have been devoted to the sources and
      emissions of Persistent Organic Pollutants (POPs) at regional and global scales.
      While significant improvements in knowledge have been achieved for some
      pesticides, the quantitative understanding of the emission processes and emission
      patterns for "non-pesticide" POPs are still considered limited. The key issues
      remaining for the non-pesticide POPs are in part determined by their general
      source classification. For industrial chemicals, such as the polychlorinated
      biphenyls (PCBs), there is considerable uncertainty with respect to the relative
      importance of atmospheric emissions from various source categories. For PCBs,
      temperature is discussed as a potential key factor influencing atmospheric
      emission levels and patterns. When it comes to the unintentional by-products of
      combustion and industrial processes (PCDD/Fs), there is still a large uncertainty
      with respect to the relative contribution of emissions from unregulated sources
      such as backyard barrel burning that requires further consideration and
      characterisation. For hexachlorobenzene (HCB), the relative importance of primary
      and secondary atmospheric emissions in controlling current atmospheric
      concentrations remains one of the key uncertainties. While these and other issues
      may remain unresolved, knowledge concerning the emissions of POPs is a
      prerequisite for any attempt to understand and predict the distribution and fate
      of these chemicals on a regional and global scale as well as to efficiently
      minimise future environmental burdens.

PMID- 14667717
TI  - Seasonal and long-term trends in atmospheric PAH concentrations: evidence and
      implications.
AB  - Atmospheric monitoring data for selected polynuclear aromatic hydrocarbons (PAHs)
      were compiled from remote, rural and urban locations in the UK, Sweden, Finland
      and Arctic Canada. The objective was to examine the seasonal and temporal trends,
      to shed light on the factors which exert a dominant influence over ambient PAH
      levels. Urban centres in the UK have concentrations 1-2 orders of magnitude
      higher than in rural Europe and up to 3 orders of magnitude higher than Arctic
      Canada. Interpretation of the data suggests that proximity to primary sources
      'drives' PAH air concentrations. Seasonality, with winter (W) > summer (S), was
      apparent for most compounds at most sites; high molecular weight compounds (e.g.
      benzo[a]pyrene) showed this most clearly and consistently. Some low molecular
      weight compounds (e.g. phenanthrene) sometimes displayed S>W seasonality at some
      rural locations. Strong W>S seasonality is linked to seasonally-dependent sources
      which are greater in winter. This implicates inefficient combustion processes,
      notably the diffusive domestic burning of wood and coal. However, sometimes
      seasonality can also be strongly influenced by broad changes in meteorology and
      air mass origin (e.g. in the Canadian Arctic). The datasets examined here suggest
      a downward trend for many PAHs at some sites, but this is not apparent for all
      sites and compounds. The inherent noise in ambient air monitoring data makes it
      difficult to derive unambiguous evidence of underlying declines, to confirm the
      effectiveness of international source reduction measures.

PMID- 14667718
TI  - Distribution of some organochlorine compounds in pine needles from Central and
      Northern Europe.
AB  - Levels of selected organochlorine compounds in pine needles were measured in two
      sampling series. The first series collected in 1989 covered Southern Germany to
      Northern Scandinavia, and the second collected in 1990 covered Czechoslovakia to
      Estonia. The levels of alpha-hexachlorocyclohexane (alpha-HCH) and
      hexachlorobenzene (HCB) were relatively uniform throughout Europe, while the
      levels of gamma-hexachlorocyclohexane (gamma-HCH) and the DDT group show higher
      levels in the southern parts of the investigated area. The deposition patterns of
      all compounds except alpha-HCH indicate a dependence on fresh release from
      diffuse or point sources rather than global fractionation. The analytes
      accumulate in the needles until senescence starts and, generally, the oldest
      needles have the highest concentrations. The accumulation rate of the analytes in
      mountain pine needles is about half that of Scots pine needles indicating the
      importance of species differences.

PMID- 14667719
TI  - Soil-air exchange of organochlorine pesticides in the Southern United States.
AB  - Soil samples were collected from 30 farms in Alabama, Louisiana and Texas during
      1999-2000 to determine residues of organochlorine pesticides (OCPs). One or more
      of the DDT compounds (p,p'-DDT, o,p'-DDT, p,p'-DDD, p,p'-DDE, o,p'-DDE) was above
      the quantitation limit (0.1 ng g(-1) dry weight) in every soil, and toxaphene was
      above the quantitation limit (3 ng g(-1)) in 26 soils. Chlordanes, dieldrin and
      hexachlorocyclohexane (HCH) isomers occurred less frequently (quantitation limits
      0.1 ng g(-1) for dieldrin and 0.05 ng g(-1) for chlordanes and HCHs). OCPs were
      measured in air at 40 cm above the soil at selected farms to investigate soil-air
      partitioning. Concentrations of OCPs in air were positively and significantly
      (P<0.001-0.004) correlated to soil concentrations for toxaphene, p,p'-DDT, o,p'
      DDT, p,p'-DDE, dieldrin, and trans-nonachlor. The regression was weaker (P=0.022)
      for cis-chlordane and not significant for trans-chlordane (P=0.43) nor gamma-HCH
      (P=0.80). Approach to soil-air equilibrium was assessed by calculating fugacities
      in the soil and air (f(s) and f(a)) for samples with quantifiable residues in
      both compartments. The fugacity fraction f(s)=0.5 at equilibrium and is <0.5 or
      >0.5 for net deposition and net volatilisation, respectively. Fugacity fractions
      varied greatly for different soil-air pairs, reflecting generally disequilibrium
      conditions. Mean fugacity fractions indicated near-equilibrium for some OCPs
      (p,p'-DDE, chlordanes, trans-nonachlor and dieldrin) and net volatilisation for
      others (p,p'-DDT, o,p'-DDT, toxaphene, gamma-HCH). Chiral analysis showed that
      enantioselective degradation of (+) or (-) o,p'-DDT in soil was accompanied by
      enrichment or depletion of the corresponding enantiomers in the overlying air,
      although there appeared to be some dilution by racemic o,p'-DDT from regional air
      transport.

PMID- 14667720
TI  - PCB in soils and estimated soil-air exchange fluxes of selected PCB congeners in
      the south of Sweden.
AB  - PCB concentrations were studied in different soils to determine the spatial
      variation over a region of approximately 11 000 km(2). PCB congener pattern was
      used to illustrate the spatial differences, as shown by principal component
      analysis (PCA). The relationship to different soil parameters was studied. PCB
      concentrations in soil showed a large variation between sampling-areas with
      median concentrations ranging between 2.3 and 332 ng g(-1) (dw). Highest
      concentrations were found at two sites with sandy soils, one with extremely high
      organic carbon content. Both sites were located on the west coast of southern
      Sweden. Soils with similar soil textures (i.e. sandy silt moraine) did not show
      any significant differences in PCB concentrations. PCB congener composition was
      shown to differ between sites, with congener patterns almost site-specific. PCB
      in air and precipitation was measured and the transfer of chemicals between the
      soil and air compartments was estimated. Soil-air fugacity quotient calculations
      showed that the PCBs in the soil consistently had a higher fugacity than the PCBs
      in the air, with a median quotient value of 2.7. The gaseous fluxes between soil
      and air were estimated using standard modelling equations and a net soil-air flux
      estimated by subtracting bulk deposition from gaseous soil-air fluxes. It was
      shown that inclusion of vertical sorbed phase transport of PCBs in the soil had a
      large effect on the direction of the net soil-air exchange fluxes.

PMID- 14667721
TI  - Air-sea gas exchange of HCHs and PCBs and enantiomers of alpha-HCH in the
      Kattegat Sea region.
AB  - Concentrations and air-water gas exchange of polychlorinated biphenyls (PCBs) and
      hexachlorocyclohexanes (HCHs) were determined in nine paired air and water
      samples. The samples were collected monthly in the Kattegat Sea between December
      1998 and November 1999. Average fugacity and flux values indicated that PCBs were
      oversaturated in the water, while HCHs were net deposited. Variations were large
      over the year, especially during spring and summer. Air parcel back trajectories
      suggested that air concentrations over the Kattegat Sea are largely dependent of
      air mass origin. Seasonal trends were detected for airborne HCHs and for PCBs in
      water. The air and water enantiomeric compositions of alpha-HCH indicated that a
      larger portion of alpha-HCH in air originated from the underlying water during
      summer than during winter.

PMID- 14667722
TI  - Evaluation of sequentially-coupled POP fluxes estimated from simultaneous
      measurements in multiple compartments of an air-water-sediment system.
AB  - Bulk atmospheric deposition fluxes, air-water exchange fluxes, particle settling
      fluxes out of the upper water column, sediment trap fluxes in deep waters, and
      sediment burial fluxes of polychlorinated biphenyls (PCBs) and polycyclic
      aromatic hydrocarbons (PAHs) were simultaneously measured in the Koster Fjord,
      eastern Skagerak, on the Swedish west coast. The aim of the study was to compare
      the magnitude and direction of the compound fluxes in the system in order to
      diagnose key fate processes. The PCB and PAH fluxes via net atmospheric
      deposition, settling particles out of the surface and through deep waters, as
      well as into the accreting underlying sediments were shown to be remarkably
      similar, agreeing within a factor of a few for any given target compound. Fluxes
      of all PCB and PAH target compounds remained fairly constant with water column
      depth. Thus there was no evidence for net desorption from sinking particles. The
      net unidirectional and near balancing of vertical fluxes suggests a net transport
      of PCBs and PAHs from the atmosphere to the continental shelf sediments in the
      Koster Fjord, which is consistent with the hypothesis that the shelf sediments
      are important sinks for these compounds.

PMID- 14667723
TI  - Current issues and uncertainties in the measurement and modelling of air
      vegetation exchange and within-plant processing of POPs.
AB  - Air-vegetation exchange of POPs is an important process controlling the entry of
      POPs into terrestrial food chains, and may also have a significant effect on the
      global movement of these compounds. Many factors affect the air-vegetation
      transfer including: the physicochemical properties of the compounds of interest;
      environmental factors such as temperature, wind speed, humidity and light
      conditions; and plant characteristics such as functional type, leaf surface area,
      cuticular structure, and leaf longevity. The purpose of this review is to
      quantify the effects these differences might have on air/plant exchange of POPs,
      and to point out the major gaps in the knowledge of this subject that require
      further research. Uptake mechanisms are complicated, with the role of each factor
      in controlling partitioning, fate and behaviour process still not fully
      understood. Consequently, current models of air-vegetation exchange do not
      incorporate variability in these factors, with the exception of temperature.
      These models instead rely on using average values for a number of environmental
      factors (e.g. plant lipid content, surface area), ignoring the large variations
      in these values. The available models suggest that boundary layer conductance is
      of key importance in the uptake of POPs, although large uncertainties in the
      cuticular pathway prevents confirmation of this with any degree of certainty, and
      experimental data seems to show plant-side resistance to be important. Models are
      usually based on the assumption that POP uptake occurs through the lipophilic
      cuticle which covers aerial surfaces of plants. However, some authors have
      recently attached greater importance to the stomatal route of entry into the leaf
      for gas phase compounds. There is a need for greater mechanistic understanding of
      air-plant exchange and the 'scaling' of factors affecting it. The review also
      suggests a number of key variables that researchers should measure in their
      experiments to allow comparisons to be made between studies in order to improve
      our understanding of what causes any differences in measured data between sites.

PMID- 14667724
TI  - Evidence for the "grasshopper" effect and fractionation during long-range
      atmospheric transport of organic contaminants.
AB  - Although there is indisputable evidence that long-range atmospheric transport
      (LRAT) of organic contaminants occurs on a global scale, uncertainties remain
      about the detailed mechanism and extent of this phenomenon as well as the
      physical-chemical properties which facilitate LRAT. In this study, we discuss how
      mass balance models and monitoring data can contribute to a fuller understanding
      of the mechanism and extent of LRAT. Specifically we address the issues of
      "grasshopping" or "hopping" (the extent to which molecules are subject to
      multiple hops as distinct from a single emission-deposition event) and "global
      fractionation" (the differing behavior of chemicals as they are transported). It
      is shown that simple mass balance models can be used to assist the interpretation
      of monitoring data while also providing an instrument that can be used to assess
      the LRAT potential and the extent of hopping that organic substances may
      experience. The available evidence supports the notion that many persistent
      organic pollutants experience varying degrees of "hopping" during their
      environmental journey and as a consequence become fractionated with distance from
      source.

PMID- 14667725
TI  - Latitudinal and seasonal capacity of the surface oceans as a reservoir of
      polychlorinated biphenyls.
AB  - The oceans play an important role as a global reservoir and ultimate sink of
      persistent organic pollutants (POPs) such as polychlorinated biphenyls congeners
      (PCBs). However, the physical and biogeochemical variables that affect the
      oceanic capacity to retain PCBs show an important spatial and temporal
      variability which have not been studied in detail, so far. The objective of this
      paper is to assess the seasonal and spatial variability of the ocean's maximum
      capacity to act as a reservoir of atmospherically transported and deposited PCBs.
      A level I fugacity model is used which incorporates the environmental variables
      of temperature, phytoplankton biomass, and mixed layer depth, as determined from
      remote sensing and from climatological datasets. It is shown that temperature,
      phytoplankton biomass and mixed layer depth influence the potential PCB reservoir
      of the oceans, being phytoplankton biomass specially important in the oceanic
      productive regions. The ocean's maximum capacities to hold PCBs are estimated.
      They are compared to a budget of PCBs in the surface oceans derived using a level
      III model that assumes steady state and which incorporates water column settling
      fluxes as a loss process. Results suggest that settling fluxes will keep the
      surface oceanic reservoir of PCBs well below its maximum capacity, especially for
      the more hydrophobic compounds. The strong seasonal and latitudinal variability
      of the surface ocean's storage capacity needs further research, because it plays
      an important role in the global biogeochemical cycles controlling the ultimate
      sink of PCBs. Because this modeling exercise incorporates variations in downward
      fluxes driven by phytoplankton and the extent of the water column mixing, it
      predicts more complex latitudinal variations in PCBs concentrations than those
      previously suggested.

PMID- 14667726
TI  - Investigating the occurrence of persistent organic pollutants (POPs) in the
      arctic: their atmospheric behaviour and interaction with the seasonal snow pack.
AB  - POPs in the Arctic are the focus of international concern due to their occurrence
      and accumulation in Arctic food webs. This paper presents an overview of the
      major pathways into the Arctic and details contemporary studies that have focused
      on the occurrence and transfer of POPs between the major Arctic compartments,
      highlighting areas where there is a lack of quantitative information. The
      behaviour of these chemicals in the Arctic atmosphere is scrutinised with respect
      to long-term trends and seasonal behaviour. Subtle differences between the PCBs
      and OC pesticides are demonstrated and related to sources outside of the Arctic
      as well as environmental processes within the Arctic. Unlike temperate regions,
      contaminant fate is strongly affected by the presence of snow and ice. A
      description of the high Arctic snow pack is given and the physical
      characteristics that determine chemical fate, namely the specific surface area of
      snow and wind driven ventilation, are discussed. Using a well-characterised fresh
      snow event observed at Alert (Canadian high Arctic) [Atmos. Environ. 36(2002)
      2767] the flux of gamma-HCH out of the snow is predicted following snow ageing.
      Under conditions of wind (10 m/s) it is estimated that approximately 75% of the
      chemical may be re-emitted to the atmosphere within 24 h following snowfall,
      compared with just approximately 5% under conditions of no wind. The implications
      of this are raised and areas of further research suggested.

PMID- 14667727
TI  - Long-range transport and global fractionation of POPs: insights from multimedia
      modeling studies.
AB  - The long-range transport of persistent organic pollutants (POPs) is investigated
      with two multimedia box models of the global system. ChemRange is a purely
      evaluative, one-dimensional steady-state (level III) model; CliMoChem is a two
      dimensional model with different temperatures, land/water ratios and vegetation
      types in different latitudinal zones. Model results are presented for three case
      studies: (i) the effect of atmospheric aerosol particles on the long-range
      transport of POPs, (ii) the effect of oceanic deposition on the long-range
      transport of different PCB congeners, (iii) the global fractionation of different
      PCB congeners. The model results for these case studies show: (i) the low
      atmospheric half-lives estimated for several organochlorine pesticides are likely
      to be inconsistent with the observed long-range transport of these compounds;
      (ii) export to the deep sea reduces the potential for long-range transport of
      highly hydrophobic compounds (but does not remove these chemicals from the
      biosphere); (iii) there are different meanings of the term global fractionation
      that refer to different aspects of the fractionation process and need to be
      distinguished. The case-study results further indicate that the influences of
      varying environmental conditions on the physicochemical properties and the
      degradation rate constants of POPs need to be determined.

PMID- 14667728
TI  - Prediction of overall persistence and long-range transport potential with
      multimedia fate models: robustness and sensitivity of results.
AB  - The hazard indicators persistence (P) and long-range transport potential (LRTP)
      are used in chemicals assessment to characterize chemicals with regard to the
      temporal and spatial extent of their environmental exposure. They are often
      calculated based on the results of multimedia fate models. The environmental and
      substance-specific input parameters of such models are subject to a range of
      methodological uncertainties and also influenced by natural variability. We
      employed probabilistic uncertainty analysis to quantify variance in P and LRTP
      predictions for chemicals with different partitioning and transport behavior.
      Variance found in the results is so large that it prevents a clear distinction
      between chemicals. Additionally, only small improvements are observed when
      evaluating the results relative to a benchmark chemical. This can be explained by
      the dominance of substance-specific parameters and the only small direct
      influence of environmental parameters on P and LRTP as model outcomes. The
      findings underline the importance of learning how environmental conditions cause
      variability in substance behavior for improved substance ranking and
      classification.

PMID- 14667729
TI  - Indicators for persistence and long-range transport potential as derived from
      multicompartment chemistry-transport modelling.
AB  - Total environmental and compartmental residence times as a measure for
      persistence as well as indicators for long-range transport potential (LRTP) have
      been derived from global geo-referenced modelling and LRTP is characterized in
      two geographic directions for the first time. A dynamic multicompartment
      chemistry-transport model (MCTM) was used to study the fate of the insecticides
      DDT and alpha-hexachlorocyclohexane (alpha-HCH) during the first 2 years upon
      entry. The indicators for LRTP were defined such as to address the tendencies of
      substance distributions to migrate ('plume displacement', PD) and to spread into
      remote areas ('spatial spreading', SS). The indicators deliver values as function
      of time upon entry. With the aim to address the effect of location of entry on
      environmental fate, scenarios of emission from the territories of seven countries
      were studied. It was found that the effect of location of entry on the spatial
      scale of countries (400-4000 km) is significant for the compartmental
      distribution and the inter-compartmental mass exchange fluxes (e.g., number of
      atmospheric cycles, 'hops'). Location of entry introduces uncertainties in the
      order of a factor of 5 for the total environmental residence time, tau(overall),
      and a factor of 5-20 for PD and SS. For the 2nd year upon entry into the
      environment, tau(overall)=317-1527 days are predicted for DDT and 101-463 days
      for alpha-HCH. The influence of location of entry does affect the substance
      ranking, i.e. we cannot simply state that DDT is more persistent than alpha-HCH,
      but for one scenario studied, application in China, the opposite is predicted.
      Precipitation patterns proved to be significant, besides other climate
      parameters, for atmospheric residence time. Integration of the location of entry
      in chemicals risk assessments is therefore recommended. In general, persistence
      and some indicators for LRTP, pertinent to their definition, refer to the fate of
      a large fraction, e.g., 63% (=1-1/e) or 90%, but not the total substance burden.
      The choice of this fraction may have the consequence of a normative step which
      defines the spatial and temporal extensions of a related chemicals risk
      assessment and may affect substance ranking.

PMID- 14667730
TI  - BETR-World: a geographically explicit model of chemical fate: application to
      transport of alpha-HCH to the Arctic.
AB  - The Berkeley-Trent (BETR)-World model, a 25 compartment, geographically explicit
      fugacity-based model is described and applied to evaluate the transport of
      chemicals from temperate source regions to receptor regions (such as the Arctic).
      The model was parameterized using GIS and an array of digital data on weather,
      oceans, freshwater, vegetation and geo-political boundaries. This version of the
      BETR model framework includes modification of atmospheric degradation rates by
      seasonally variable hydroxyl radical concentrations and temperature. Degradation
      rates in all other compartments vary with seasonally changing temperature.
      Deposition to the deep ocean has been included as a loss mechanism. A case study
      was undertaken for alpha-HCH. Dynamic emission scenarios were estimated for each
      of the 25 regions. Predicted environmental concentrations showed good agreement
      with measured values for the northern regions in air, and fresh and oceanic water
      and with the results from a previous model of global chemical fate. Potential for
      long-range transport and deposition to the Arctic region was assessed using a
      Transfer Efficiency combined with estimated emissions. European regions and the
      Orient including China have a high potential to contribute alpha-HCH
      contamination in the Arctic due to high rates of emission in these regions
      despite low Transfer Efficiencies. Sensitivity analyses reveal that the
      performance and reliability of the model is strongly influenced by parameters
      controlling degradation rates.

PMID- 14667731
TI  - Modeling transport and deposition of contaminants to ecosystems of concern: a
      case study for the Laurentian Great Lakes.
AB  - Transfer efficiency (TE) is introduced as a model output that can be used to
      characterize the relative ability of chemicals to be transported in the
      environment and deposited to specific target ecosystems. We illustrate this
      concept by applying the Berkeley-Trent North American contaminant fate model
      (BETR North America) to identify organic chemicals with properties that result in
      efficient atmospheric transport and deposition to the Laurentian Great Lakes. By
      systematically applying the model to hypothetical organic chemicals that span a
      wide range of environmental partitioning properties, we identify combinations of
      properties that favor efficient transport and deposition to the Lakes. Five
      classes of chemicals are identified based on dominant transport and deposition
      pathways, and specific examples of chemicals in each class are identified and
      discussed. The role of vegetation in scavenging chemicals from the atmosphere is
      assessed, and found to have a negligible influence on transfer efficiency to the
      Great Lakes. Results indicate chemicals with octanol-water (K(ow)) and air-water
      (K(aw)) partition coefficients in the range of 10(5)-10(7) and 10(-4)-10(-1)
      combine efficient transport and deposition to the Great Lakes with potential for
      biaccumulation in the aquatic food web once they are deposited. A method of
      estimating the time scale for atmospheric transport and deposition process is
      suggested, and the effects of degrading reactions in the atmosphere and
      meteorological conditions on transport efficiency of different classes of
      chemicals are discussed. In total, this approach provides a method of identifying
      chemicals that are subject to long-range transport and deposition to specific
      target ecosystems as a result of their partitioning and persistence
      characteristics. Supported by an appropriate contaminant fate model, the approach
      can be applied to any target ecosystem of concern.

PMID- 14667732
TI  - Modelling the fate of persistent organic pollutants in Europe: parameterisation
      of a gridded distribution model.
AB  - A regionally segmented multimedia fate model for the European continent is
      described together with an illustrative steady-state case study examining the
      fate of gamma-HCH (lindane) based on 1998 emission data. The study builds on the
      regionally segmented BETR North America model structure and describes the
      regional segmentation and parameterisation for Europe. The European continent is
      described by a 5 degrees x5 degrees grid, leading to 50 regions together with
      four perimetric boxes representing regions buffering the European environment.
      Each zone comprises seven compartments including; upper and lower atmosphere,
      soil, vegetation, fresh water and sediment and coastal water. Inter-regions flows
      of air and water are described, exploiting information originating from GIS
      databases and other georeferenced data. The model is primarily designed to
      describe the fate of Persistent Organic Pollutants (POPs) within the European
      environment by examining chemical partitioning and degradation in each region,
      and inter-region transport either under steady-state conditions or fully
      dynamically. A test case scenario is presented which examines the fate of
      estimated spatially resolved atmospheric emissions of lindane throughout Europe
      within the lower atmosphere and surface soil compartments. In accordance with the
      predominant wind direction in Europe, the model predicts high concentrations
      close to the major sources as well as towards Central and Northeast regions.
      Elevated soil concentrations in Scandinavian soils provide further evidence of
      the potential of increased scavenging by forests and subsequent accumulation by
      organic-rich terrestrial surfaces. Initial model predictions have revealed a
      factor of 5-10 underestimation of lindane concentrations in the atmosphere. This
      is explained by an underestimation of source strength and/or an underestimation
      of European background levels. The model presented can further be used to predict
      deposition fluxes and chemical inventories, and it can also be adapted to provide
      characteristic travel distances and overall environmental persistence, which can
      be compared with other long-range transport prediction methods.

PMID- 14667733
TI  - Evaluating multimedia/multipathway model intake fraction estimates using POP
      emission and monitoring data.
AB  - This paper presents a structured evaluation of a novel multimedia chemical fate
      and multi-pathway human exposure model for Western Europe, IMPACT 2002, using
      data for PCDD/F congeners. PCDD/F congeners provide an illustration of the
      potential use of POPs (Persistent Organic Pollutant) data for the evaluation of
      such models. Based on available emission estimates, model predictions with and
      without spatial resolution are evaluated at three different stages against
      monitored data: at environmental contamination levels, food exposure
      concentration, and in terms of human intake fractions (iF): the fraction of an
      emission that is taken in by the population. The iF is approximately 3.5.10(-3)
      for emissions of dioxin in Western Europe. This iF compares well to the
      traditional non-spatial multi-media/-pathway model predictions of 3.9.10(-3) for
      the same region and to 2.10(-3) for the USA. Approximately 95% of the intake from
      Western European emissions occurs within the same region, 5% being transferred
      out of the region in terms of food contaminants and atmospheric advective
      transport.

PMID- 14667734
TI  - Numerical evaluation of the PCBs transport over the Northern Hemisphere.
AB  - The numerical evaluation of selected PCB congener (28, 118, 153, 180) transport
      over the Northern Hemisphere is carried out for 1996 using MSCE-POP model. This
      model is a multicompartment three-dimensional one and includes various
      environmental media such as the atmosphere, soil, vegetation, seawater, and sea
      ice. The spatial resolution is 2.5 degrees x2.5 degrees for all media except
      marine one (1.25 degrees x1.25 degrees ). The main model output information is
      deposition fluxes, spatial distribution of concentrations in environmental media,
      pathways and source-receptor relationships. Calculation results are analysed for
      the whole hemisphere and the Arctic region. In particular, this gives an
      opportunity to estimate the contributions of individual emission source groups to
      the Arctic pollution. The reliability of the model assessment is analysed by
      comparison between calculated and observed data.

PMID- 14667735
TI  - Effects of time-averaging climate parameters on predicted multicompartmental fate
      of pesticides and POPs.
AB  - With the aim to investigate the justification of time-averaging of climate
      parameters in multicompartment modelling the effects of various climate
      parameters and different modes of entry on the predicted substances' total
      environmental burdens and the compartmental fractions were studied. A simple, non
      steady state zero-dimensional (box) mass-balance model of intercompartmental mass
      exchange which comprises four compartments was used for this purpose. Each two
      runs were performed, one temporally unresolved (time-averaged conditions) and a
      time-resolved (hourly or higher) control run. In many cases significant
      discrepancies are predicted, depending on the substance and on the parameter. We
      find discrepancies exceeding 10% relative to the control run and up to an order
      of magnitude for prediction of the total environmental burden from neglecting
      seasonalities of the soil and ocean temperatures and the hydroxyl radical
      concentration in the atmosphere and diurnalities of atmospheric mixing depth and
      the hydroxyl radical concentration in the atmosphere. Under some conditions it
      was indicated that substance sensitivity could be explained by the magnitude of
      the sink terms in the compartment(s) with parameters varying. In general,
      however, any key for understanding substance sensitivity seems not be linked in
      an easy manner to the properties of the substance, to the fractions of its burden
      or to the sink terms in either of the compartments with parameters varying.
      Averaging of diurnal variability was found to cause errors of total environmental
      residence time of different sign for different substances. The effects of time
      averaging of several parameters are in general not additive but synergistic as
      well as compensatory effects occur. An implication of these findings is that the
      ranking of substances according to persistence is sensitive to time resolution on
      the scale of hours to months. As a conclusion it is recommended to use high
      temporal resolution in multi-media modelling.

PMID- 14667736
TI  - How do you sleep at night, Mr Blair?

PMID- 14667737
TI  - Are we ready for a paradigm change in cervical cancer screening?

PMID- 14667738
TI  - Is the diagnosis important for the treatment of patients with shoulder
      complaints?

PMID- 14667739
TI  - Unhappy neighbourhood: spatial genome organisation and lymphomagenesis in B
      cells.

PMID- 14667740
TI  - The West Nile season.

PMID- 14667741
TI  - Management of women who test positive for high-risk types of human
      papillomavirus: the HART study.
AB  - BACKGROUND: Certain types of human papillomavirus (HPV) are the primary cause of
      almost all cervical cancers. HPV testing of cervical smears is more sensitive but
      less specific than cytology for detecting high-grade cervical intraepithelial
      neoplasia (CIN2+). HPV testing as a primary screening approach requires efficient
      management of HPV-positive women with negative or borderline cytology. We aimed
      to compare the detection rate and positive predictive values of HPV assay with
      cytology and to determine the best management strategy for HPV-positive women.
      METHODS: We did a multicentre screening study of 11085 women aged 30-60 years.
      Women with borderline cytology and women positive for high-risk HPV with negative
      cytology were randomised to immediate colposcopy or to surveillance by repeat HPV
      testing, cytology, and colposcopy at 12 months. FINDINGS: HPV testing was more
      sensitive than borderline or worse cytology (97.1% vs 76.6%, p=0.002) but less
      specific (93.3% vs 95.8%, p<0.0001) for detecting CIN2+. Of 825 randomised women,
      surveillance at 12 months was as effective as immediate colposcopy. In women
      positive for HPV at baseline, who had surveillance, 73 (45%) of 164 women with
      negative cytology and eight (35%) of 23 women with borderline cytology were HPV
      negative at 6-12 months. No CIN2+ was found in these women, nor in women with an
      initial negative HPV test with borderline (n=211) or mild (32) cytology.
      INTERPRETATION: HPV testing could be used for primary screening in women older
      than 30 years, with cytology used to triage HPV-positive women. HPV-positive
      women with normal or borderline cytology (about 6% of screened women) could be
      managed by repeat testing after 12 months. This approach could potentially
      improve detection rates of CIN2+ without increasing the colposcopy referral rate.

PMID- 14667742
TI  - Cardiac catheterisation guided by MRI in children and adults with congenital
      heart disease.
AB  - BACKGROUND: Fluoroscopically guided cardiac catheterisation is an essential tool
      for diagnosis and treatment of congenital heart disease. Drawbacks include poor
      soft tissue visualisation and exposure to radiation. We describe the first 16
      cases of a novel method of cardiac catheterisation guided by MRI with
      radiographic support. METHODS: In our cardiac catheterisation laboratory, we
      combine magnetic resonance and radiographic imaging facilities. We used MRI to
      measure flow and morphology, and real-time MRI sequences to visualise balloon
      angiographic catheters. 12 patients underwent diagnostic cardiac catheterisation,
      two had interventional cardiac catheterisations, and for two patients, MRI was
      used to plan radiofrequency ablation for treatment of tachyarrhythmias. FINDINGS:
      In 14 patients, some or all of the cardiac catheterisation was guided by MRI. In
      two patients undergoing radiofrequency ablation, catheters were manipulated with
      use of fluoroscopic guidance and outcome was assessed with MRI. All patients
      received lower amounts of radiation than controls. There was some discrepancy
      between pulmonary vascular resistance calculated by flow derived from MRI and the
      traditional Fick method. We were able to superimpose fluoroscopic images of
      electro physiology electrode catheters on the three dimensional MRI of the
      cardiac anatomy. INTERPRETATION: We have shown that cardiac catheterisation
      guided by MRI is safe and practical in a clinical setting, allows better soft
      tissue visualisation, provides more pertinent physiological information, and
      results in lower radiation exposure than do fluoroscopically guided procedures.
      MRI guidance could become the method of choice for diagnostic cardiac
      catheterisation in patients with congenital heart disease, and an important tool
      in interventional cardiac catheterisation and radiofrequency ablation.

PMID- 14667743
TI  - Effect of ultrasound screening on the rate of first operative procedures for
      developmental hip dysplasia in Germany.
AB  - BACKGROUND: Ultrasound screening for developmental hip dysplasia and early
      conservative treatment might prevent later hip operations. A national hip
      ultrasound-screening programme, undertaken during the first 6 weeks of life, was
      introduced across Germany in 1996 and was continued for 5 years. We assessed the
      rate of first operation on the hip during this programme. METHODS: A national
      active surveillance programme of initial operations for developmental hip
      dysplasia was started in 1997 and continued for 5 years. Screening participation
      was assessed by a random digit dialing telephone survey. Cases were children aged
      between 10 weeks and 5 years at first operation, who had had no underlying
      disease leading to developmental hip dysplasia. Completeness of case
      ascertainment was validated with a capture-recapture study in a representative
      subsample. Calculated incidences were compared with previously established rates.
      FINDINGS: About 90% of all children were screened. 147 cases in the first year,
      and between 81 and 105 for subsequent years were reported. Treatment included
      closed reductions 353 (66%), open reductions 61 (11%), and osteotomies 121 (23%).
      Developmental hip dysplasia was diagnosed by ultrasound before 6 weeks of age in
      272 (55%) of cases, 64 (13%) were screened at the recommended time but had normal
      findings, 70 (14%) had delayed screening, and 89 (18%) were not screened. Capture
      recapture estimates suggested that 52% of cases were reported. The corrected
      incidence for first operation was 0.26 per 1000 livebirths (95% CI 0.22-0.32).
      INTERPRETATION: Ultrasound screening seems to prevent many, but not all,
      operations for developmental hip dysplasia. Rates of timely screening (ie, before
      6 weeks of age) and training of doctors in ultrasound screening need to be
      improved.

PMID- 14667745
TI  - Acquisition of 16S rRNA methylase gene in Pseudomonas aeruginosa.
AB  - BACKGROUND: Bacteria develop resistance to aminoglycosides by producing
      aminoglycoside-modifying enzymes such as acetyltransferase, phosphorylase, and
      adenyltransferase. These enzymes, however, cannot confer consistent resistance to
      various aminoglycosides because of their substrate specificity. Notwithstanding,
      a Pseudomonas aeruginosa strain AR-2 showing high-level resistance (minimum
      inhibitory concentration >1024 mg/L) to various aminoglycosides was isolated
      clinically. We aimed to clone and characterise the genetic determinant of this
      resistance. METHODS: We used conventional methods for DNA manipulation,
      susceptibility testing, and gene analyses to clone and characterise the genetic
      determinant of the resistance seen. PCR detection of the gene was also done on a
      stock of P aeruginosa strains that were isolated clinically since 1997. FINDINGS:
      An aminoglycoside-resistance gene, designated rmtA, was identified in P
      aeruginosa AR-2. The Escherichia coli transformant and transconjugant harbouring
      the rmtA gene showed very high-level resistance to various aminoglycosides,
      including amikacin, tobramycin, isepamicin, arbekacin, kanamycin, and gentamicin.
      The 756-bp nucleotide rmtA gene encoded a protein, RmtA. This protein showed
      considerable similarity to the 16S rRNA methylases of aminoglycoside-producing
      actinomycetes, which protect bacterial 16S rRNA from intrinsic aminoglycosides by
      methylation. Incorporation of radiolabelled methyl groups into the 30S ribosome
      was detected in the presence of RmtA. Of 1113 clinically isolated P aeruginosa
      strains, nine carried the rmtA gene, as shown by PCR analyses. INTERPRETATION:
      Our findings strongly suggest intergeneric lateral gene transfer of 16S rRNA
      methylase gene from some aminoglycoside-producing microorganisms to P aeruginosa.
      Further dissemination of the rmtA gene in nosocomial bacteria could be a matter
      of concern in the future.

PMID- 14667746
TI  - Peritoneal dialysis and an inguinal hernia.

PMID- 14667747
TI  - A girl with a sore ear.

PMID- 14667748
TI  - Effects of a SARS-associated coronavirus vaccine in monkeys.
AB  - The causative agent of severe acute respiratory syndrome (SARS) has been
      identified as a new type of coronavirus. Here, we have investigated the ability
      of adenoviral delivery of codon-optimised SARS-CoV strain Urbani structural
      antigens spike protein S1 fragment, membrane protein, and nucleocapsid protein to
      induce virus-specific broad immunity in rhesus macaques. We immunised rhesus
      macaques intramuscularly with a combination of the three Ad5-SARS-CoV vectors or
      a control vector and gave a booster vaccination on day 28. The vaccinated animals
      all had antibody responses against spike protein S1 fragment and T-cell responses
      against the nucleocapsid protein. All vaccinated animals showed strong
      neutralising antibody responses to SARS-CoV infection in vitro. These results
      show that an adenoviral-based vaccine can induce strong SARS-CoV-specific immune
      responses in the monkey, and hold promise for development of a protective vaccine
      against the SARS causal agent.

PMID- 14667749
TI  - Screening for hereditary haemochromatosis within families and beyond.
AB  - Screening programmes for haemochromatosis that include follow-up identification
      of relatives are claimed to be cost effective. We assessed uptake of screening by
      first-degree relatives of two groups of index cases: people homozygous for the
      C282Y mutation ascertained by genetic screening of blood donors; and patients
      presenting clinically with haemochro matosis. Only 40 (24%) of 165 relatives of
      blood donors had been tested. By contrast, testing uptake in 121 relatives of
      patients diagnosed clinically was more than double that (53%), despite
      unstructured provision of genetic information. A substantial number of untested
      relatives had undiagnosed iron overload. Overall efficacy of population screening
      for haemochromatosis is undermined by these observations.

PMID- 14667750
TI  - Hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cause of cancer, and its
      incidence is increasing worldwide because of the dissemination of hepatitis B and
      C virus infection. Patients with cirrhosis are at the highest risk and should be
      monitored every 6 months. Surveillance can lead to diagnosis at early stages,
      when the tumour might be curable by resection, liver transplantation, or
      percutaneous treatment. In the West and Japan, these treatments can be applied to
      30% of patients, and result in 5-year survival rates higher than 50%. Resection
      is indicated among patients who have one tumour and well-preserved liver
      function. Liver transplantation benefits patients who have decompensated
      cirrhosis and one tumour smaller than 5 cm or three nodules smaller than 3 cm,
      but donor shortage greatly limits its applicability. This difficulty might be
      overcome by living donation. Most HCC patients are diagnosed at advanced stages
      and receive palliative treatments, which have been assessed in the setting of 63
      randomised controlled trials during the past 25 years. Meta-analysis shows that
      only chemoembolisation improves survival in well-selected patients with
      unresectable HCC.

PMID- 14667751
TI  - Human Taeniasis and cysticercosis in Asia.
AB  - CONTEXT: Human Taeniasis caused by the pork, Taenia solium, or beef, T saginata,
      tapeworm arises after eating pork or beef contaminated with metacestodes, the
      larval stage of these parasites. Taeniasis with T solium can lead to
      neurocysticercosis and threaten others by accidental ingestion of eggs released
      from asymptomatic Taeniasis patients. The 2003 World Health Assembly declared
      that T solium is of worldwide public-health importance, and that it is an
      eradicable parasitic disease worldwide. Adult taeniid tapeworms expelled from
      people in almost all Asian countries appeared to be T saginata (the so-called
      Asian Taenia), even though they ate pork. The organism is now named T asiatica,
      and has been found in Taiwan, Korea, China, Vietnam, and Indonesia. But it has
      been difficult to differentiate T saginata from beef and Asian Taenia from pork.
      STARTING POINT: Marshall Lightowlers and colleagues (Int J Parasitol 2003; 33:
      1207-17) recently demonstrated that recombinant oncosphere vaccines against
      several taeniid cestodes, including T ovis, T saginata, T solium, and
      Echinococcus granulosus, are highly effective. Protection was almost 100%, in the
      laboratory and in the field. These researchers found several common features,
      including a predicted secretory signal sequence, and one or two copies of a
      fibronectin type III domain, each encoded by separate exons within the associated
      gene. WHERE NEXT? Molecular and immunological techniques, including vaccine
      research and development of animal models for differentiation of taeniid species
      in humans, have greatly advanced over the past decade. The clinical importance of
      infections by these taeniids, including T asiatica, in humans, and the potential
      for cysticercosis attributable to T asiatica in humans, needs further study.

PMID- 14667752
TI  - Anaesthesia, surgery, and challenges in postoperative recovery.
AB  - Surgical injury can be followed by pain, nausea, vomiting and ileus, stress
      induced catabolism, impaired pulmonary function, increased cardiac demands, and
      risk of thromboembolism. These problems can lead to complications, need for
      treatment in hospital, postoperative fatigue, and delayed convalescence.
      Development of safe and short-acting anaesthetics, improved pain relief by early
      intervention with multimodal analgesia, and stress reduction by regional
      anaesthetic techniques, beta-blockade, or glucocorticoids have provided important
      possibilities for enhanced recovery. When these techniques are combined with a
      change in perioperative care a pronounced enhancement of recovery and decrease in
      hospital stay can be achieved, even in major operations. The anaesthetist has an
      important role in facilitating early postoperative recovery by provision of
      minimally-invasive anaesthesia and pain relief, and by collaborating with
      surgeons, surgical nurses, and physiotherapists to reduce risk and pain.

PMID- 14667753
TI  - Estimates of HIV-1 prevalence from national population-based surveys as a new
      gold standard.

PMID- 14667754
TI  - Sustainable schistosomiasis control--the way forward.

PMID- 14667755
TI  - One should never forget about heredity.

PMID- 14667756
TI  - The EUROPA trial.

PMID- 14667757
TI  - The EUROPA trial.

PMID- 14667758
TI  - The EUROPA trial.

PMID- 14667759
TI  - The EUROPA trial.

PMID- 14667761
TI  - Combine EUROPA and HOPE.

PMID- 14667762
TI  - Autonomy and anorexia nervosa.

PMID- 14667763
TI  - Securing Iraq's health.

PMID- 14667764
TI  - Securing Iraq's health.

PMID- 14667765
TI  - Food crisis and AIDS: the Indian perspective.

PMID- 14667766
TI  - Spotted-fever-group rickettsioses in north Asia.

PMID- 14667767
TI  - Power shutdowns and biological standards.

PMID- 14667768
TI  - Hip protectors.

PMID- 14667769
TI  - Training of skilled birth attendants in Bangladesh.

PMID- 14667770
TI  - Monitoring mortality in general practice: a simpler solution?

PMID- 14667771
TI  - Constipation as a presenting symptom of multiple sclerosis.

PMID- 14667772
TI  - Adults with congenital heart disease.

PMID- 14667773
TI  - Putting Jenner back in his place.

PMID- 14667775
TI  - Putting Jenner back in his place.

PMID- 14667776
TI  - Veracity in medicine.

PMID- 14667778
TI  - Smoking targets.

PMID- 14667780
TI  - Some steps toward a central theory of ecosystem dynamics.
AB  - Ecology is said by many to suffer for want of a central theory, such as Newton's
      laws of motion provide for classical mechanics or Schroedinger's wave equation
      provides for quantum physics. From among a plurality of contending laws to govern
      ecosystem behavior, the principle of increasing ascendency shows some early
      promise of being able to address the major questions asked of a theory of
      ecosystems, including, "How do organisms come to be distributed in time and
      space?, what accounts for the log-normal distribution of species numbers?, and
      how is the diversity of ecosystems related to their stability, resilience and
      persistence?" While some progress has been made in applying the concept of
      ascendency to the first issue, more work is needed to articulate exactly how it
      relates to the latter two. Accordingly, seven theoretical tasks are suggested
      that could help to establish these connections and to promote further
      consideration of the ascendency principle as the kernel of a theory of
      ecosystems.

PMID- 14667781
TI  - Comparative receptor surface analysis of octopaminergic antagonists for the
      locust neuronal octopamine receptor.
AB  - In drug discovery, it is common to have measured activity data for a set of
      compounds acting upon a particular protein but not to have knowledge of the three
      dimensional structure of the protein active site. In the absence of such three
      dimensional information, one can attempt to build a hypothetical model of the
      receptor site that can provide insight about receptor site characteristics. Such
      a model is known as a comparative receptor surface analysis (CoRSA) model, which
      provides compact and quantitative descriptors which capture three-dimensional
      information about a putative receptor site. The quantitative structure-activity
      relationship (QSAR) of a set of 20 antagonists for octopamine (OA) receptor 3 in
      locust nervous tissue, was analyzed using CoRSA. Three-dimensional energetics
      descriptors were calculated from receptor surface model (RSM)-ligand interaction
      and these three-dimensional descriptors were used in QSAR analysis. The
      predictive character of the QSAR was further assessed using 24 agonists for OA
      receptor as test molecules. An RSM was generated using some subset of the most
      active structures and the results provided useful information in the
      characterization and differentiation of OA receptor.

PMID- 14667782
TI  - Photosynthetic models with maximum entropy production in irreversible charge
      transfer steps.
AB  - Steady-state bacterial photosynthesis is modelled as cyclic chemical reaction and
      is examined with respect to overall efficiency, power transfer efficiency, and
      entropy production. A nonlinear flux-force relationship is assumed. The simplest
      two-state kinetic model bears complete analogy with the performance of an ideal
      (zero ohmic resistance of the P-N junction) solar cell. In both cases power
      transfer to external load is much higher than the 50% allowed by the impedance
      matching theorem for the linear flux-force relationship. When maximum entropy
      production is required in the transition with a load, one obtains high optimal
      photochemical yield of 97% and power transfer efficiency of 91%. In more complex
      photosynthetic models, entropy production is maximized in all irreversible
      electron/proton (non-slip) transitions in an iterative procedure. The resulting
      steady-state is stable with respect to an extremely wide range of initial values
      for forward rate constants. Optimal proton current increases proportionally to
      light intensity and decreases with an increase in the proton-motive force (the
      backpressure effect). Optimal affinity transfer efficiency is very high and
      nearly perfectly constant for different light absorption rates and for different
      electrochemical proton gradients. Optimal overall efficiency (of solar into
      proton-motive power) ranges from 10% (bacteriorhodopsin) to 19% (chlorophyll
      based bacterial photosynthesis). Optimal time constants in a photocycle span a
      wide range from nanoseconds to milliseconds, just as corresponding experimental
      constants do. We conclude that photosynthetic proton pumps operate close to the
      maximum entropy production mode, connecting biological to thermodynamic evolution
      in a coupled self-amplifying process.

PMID- 14667783
TI  - Artificial neural networks for prediction of mycobacterial promoter sequences.
AB  - A multilayered feed-forward ANN architecture trained using the error-back
      propagation (EBP) algorithm has been developed for predicting whether a given
      nucleotide sequence is a mycobacterial promoter sequence. Owing to the high
      prediction capability ( congruent with 97%) of the developed network model, it
      has been further used in conjunction with the caliper randomization (CR) approach
      for determining the structurally/functionally important regions in the promoter
      sequences. The results obtained thereby indicate that: (i) upstream region of -35
      box, (ii) -35 region, (iii) spacer region and, (iv) -10 box, are important for
      mycobacterial promoters. The CR approach also suggests that the -38 to -29 region
      plays a significant role in determining whether a given sequence is a
      mycobacterial promoter. In essence, the present study establishes ANNs as a tool
      for predicting mycobacterial promoter sequences and determining
      structurally/functionally important sub-regions therein.

PMID- 14667784
TI  - Rival penalized competitive learning (RPCL): a topology-determining algorithm for
      analyzing gene expression data.
AB  - DNA arrays have become the immediate choice in the analysis of large-scale
      expression measurements. Understanding the expression pattern of genes provide
      functional information on newly identified genes by computational approaches.
      Gene expression pattern is an indicator of the state of the cell, and abnormal
      cellular states can be inferred by comparing expression profiles. Since co
      regulated genes, and genes involved in a particular pathway, tend to show similar
      expression patterns, clustering expression patterns has become the natural method
      of choice to differentiate groups. However, most methods based on cluster
      analysis suffer from the usual problems (i) dead units, and (ii) the problem of
      determining the correct number of clusters (k) needed to classify the data.
      Selecting the k has been an open problem of pattern recognition and statistics
      for decades. Since clustering reveals similar patterns present in the data,
      fixing this number strongly influences the quality of the result. While there is
      no theoretical solution to this problem, the number of clusters can be decided by
      a heuristic clustering algorithm called rival penalized competitive learning
      (RPCL). We present a novel implementation of RPCL that transforms the correct
      number of clusters problem to the tractable problem of clustering based on the
      degree of similarity. This is biologically significant since our implementation
      clusters functionally co-regulated genes and genes that present similar patterns
      of expression. This new approach reveals potential genes that are co-involved in
      a biological process. This implementation of the RPCL algorithm is useful in
      differentiating groups involved in concerted functional regulation and helps to
      progressively home into patterns, which are closely similar.

PMID- 14667785
TI  - Use of a novel Hill-climbing genetic algorithm in protein folding simulations.
AB  - We have developed a novel Hill-climbing genetic algorithm (GA) for simulation of
      protein folding. The program (written in C) builds a set of Cartesian points to
      represent an unfolded polypeptide's backbone. The dihedral angles determining the
      chain's configuration are stored in an array of chromosome structures that is
      copied and then mutated. The fitness of the mutated chain's configuration is
      determined by its radius of gyration. A four-helix bundle was used to optimise
      simulation conditions, and the program was compared with other, larger, genetic
      algorithms on a variety of structures. The program ran 50% faster than other GA
      programs. Overall, tests on 100 non-redundant structures gave comparable results
      to other genetic algorithms, with the Hill-climbing program running from between
      20 and 50% faster. Examples including crambin, cytochrome c, cytochrome B and
      hemerythrin gave good secondary structure fits with overall alpha carbon atom rms
      deviations of between 5 and 5.6 A with an optimised hydrophobic term in the
      fitness function.

PMID- 14667786
TI  - Study on the relationship between intake of trace elements and breast cancer
      mortality with chemometric methods.
AB  - Several chemometric methods were employed to survey the interaction among the
      trace elements and the relationship between the intake of these elements and the
      breast cancer mortality. It is indicated that there are strong interactions among
      the trace elements so as to form a dynamic balance; the intake of Cr is the most
      important factor that could cause the increase of breast cancer mortality; no
      definite relation can be observed between the intake of Cu and that of Zn.
      However, either the ratio of the intake of Cu and that of Zn or the intake of Cd
      could show a certain state of dynamic balance among some of the trace elements.
      Comparison of the analytical methods reveals that it is important to select a
      suitable method so as to obtain the most appropriate explanation.

PMID- 14667787
TI  - AIDS in Africa: the impact of coinfections on the pathogenesis of HIV-1
      infection.
AB  - The intimate relationship between the HIV-1 life-cycle and the activation state
      of cells supporting viral replication results in a dynamic interaction between
      coinfections and HIV-1 replication in dually infected people. The immunologic
      impact of recurrent coinfections has the potential to increase viral replication,
      viral genotypic heterogeneity and CD4 T lymphocyte loss, leading to accelerated
      decline in immune function, reduced survival and increased HIV-1 transmission
      risk. These effects may play a particularly significant role in the HIV-1
      epidemic in sub-Saharan Africa. The mechanisms underlying these effects on virus
      host dynamics are reviewed and data describing the impact of tuberculosis,
      malaria, schistosomiasis and genital ulceration on HIV-1 infection are presented.

PMID- 14667788
TI  - Global epidemiology of paediatric tuberculosis.
AB  - Tuberculosis is one of the major infections affecting children worldwide. It
      causes significant morbidity and mortality, especially in infants and young
      children. Factors such as overcrowding, poverty and the HIV epidemic have all
      contributed to the resurgence of tuberculosis globally. The highest rates of
      tuberculosis occur in resource-poor countries and over the last decade case
      notifications in children have been increasing steadily, particularly in Sub
      Saharan Africa. Mycobacterium tuberculosis infects millions of children worldwide
      every year, yet accurate information on the extent and distribution of disease in
      children is not available for most of the world. We describe some of the unique
      aspects of tuberculosis infection in children and review the epidemiology of
      disease in children worldwide.

PMID- 14667789
TI  - Severe acute respiratory syndrome in Taiwan: analysis of epidemiological
      characteristics in 29 cases.
AB  - OBJECTIVES: To describe the clinical characteristics and outcomes of patients
      with severe acute respiratory syndrome (SARS). METHODS: Between March 28 and June
      30 '2003, 29 patients with probable SARS seen at Shin Kong Wu Ho-Su Memorial
      Hospital, Taipei, were analysed. RESULTS: Presenting symptoms included fever
      (100%), cough (69.0%), chills or rigor (62.1%), and shortness of breath (41.4%).
      Mean days to defervescence were 6.8+/-2.9 days, but fever recurred in 15 patients
      (51.7%) at 10.9+/-3.4 days. Common laboratory features included lymphopenia
      (72.4%), thrombocytopenia (34.5%) and elevated C-reactive protein (CRP), lactate
      dehydrogenase (LDH), and aspartate aminotransferase (AST) (93.1, 62.1, 44.8%,
      respectively). All patients except one had initial abnormal chest radiographs and
      20 (69.0%) had radiological worsening at 7.5+/-2.6 days. Nine patients (31.0%)
      subsequently required mechanical ventilation with four deaths (13.8%). Most
      patients with clinical deterioration responded to pulse corticosteroid therapy
      (14 out of 17) but six complicated with nosocomial infections. The risk factors
      associated with severe disease were presence of diarrhoea, high peak LDH and CRP,
      high AST and creatine kinase on admission and high peak values. CONCLUSIONS:
      Prudent corticosteroid use, vigilant microbiological surveillance and appropriate
      antibiotics coverage are the key to successful treatment.

PMID- 14667790
TI  - Evaluation of outpatient treatment with ertapenem in a double blind controlled
      clinical trial of complicated skin/skin structure infections.
AB  - OBJECTIVES: The patient characteristics and the efficacy and safety of ertapenem
      1 g once daily vs. piperacillin-tazobactam 13.5 g divided Q6H were examined in
      patients who received outpatient parenteral antimicrobial therapy (OPAT) during a
      clinical trial of complicated skin/skin structure infections. METHODS: The
      population analyzed included 363 patients treated at US sites in a large
      randomized double-blind study. RESULTS: In this analysis, 146 (40%) patients at
      19 (66%) sites were managed by OPAT. A lower proportion of treated patients who
      received OPAT had severe infection (12% vs. 20%, P=0.03). In evaluable patients
      managed by OPAT, 45 (83.3%) of 54 treated with ertapenem and 41 (82.0%) of 50
      treated with piperacillin-tazobactam were cured at the test of cure assessment 10
      21 days post-therapy (OR 1.2 (95% CI, 0.4-3.2), P=0.78). The safety profile of
      both drugs was generally similar; diarrhoea was the most common adverse event in
      both groups. CONCLUSIONS: In this trial of complicated skin/skin structure
      infection, OPAT was commonly used by US investigators. Among patients who
      received OPAT, ertapenem 1 g daily was as effective as piperacillin-tazobactam
      3.375 g Q6H.

PMID- 14667791
TI  - Antibacterial resistance among children with community-acquired respiratory tract
      infections (PROTEKT 1999-2000).
AB  - OBJECTIVE: To determine the susceptibility of bacterial respiratory tract
      pathogens, isolated from children (0-12 years) as part of the global PROTEKT
      surveillance study (1999-2000), to a range of antibacterials, including the
      ketolide telithromycin. METHODS: Minimum inhibitory concentrations of the
      antibacterials studied were determined at a central laboratory using the NCCLS
      microdilution broth method. Macrolide resistance mechanisms were detected by PCR.
      RESULTS: Of 779 Streptococcus pneumoniae isolates worldwide, 43% were non
      susceptible to penicillin (18% intermediate; 25% resistant) and 37% were
      resistant to erythromycin, with considerable intercountry variation. Eighteen per
      cent of 653 Haemophilus influenzae and >90% of 316 Moraxella catarrhalis isolates
      produced beta-lactamase. Of 640 Streptococcus pyogenes isolates, 10% were
      resistant to erythromycin, with considerable intercountry variation. All S.
      pneumoniae and 99.8% of H. influenzae isolates were susceptible to telithromycin
      using breakpoints proposed to the NCCLS (<or=1 and <or=4 mg/L, respectively). All
      M. catarrhalis and 97% of S. pyogenes and isolates were susceptible to <or=1 mg/L
      telithromycin. CONCLUSIONS: Antibacterial resistance complicates the empirical
      treatment of respiratory tract infections in children and requires continued
      monitoring. Telithromycin may be a useful therapeutic alternative as it is highly
      active against strains exhibiting various resistance phenotypes.

PMID- 14667792
TI  - Antimicrobial susceptibility among community-acquired respiratory tract pathogens
      in the USA: data from PROTEKT US 2000-01.
AB  - OBJECTIVES: The PROTEKT US surveillance program (Prospective Resistant Organism
      Tracking and Epidemiology for the Ketolide Telithromycin in the United States)
      commenced in 2000 to document the emergence and spread of antimicrobial
      resistance among respiratory tract pathogens in the United States. METHODS:
      During 2000-2001, 206 centers from 154 cities/metropolitan areas collected 16,727
      clinical isolates (Streptococcus pneumoniae, n=10103, Streptococcus pyogenes,
      n=3918, Haemophilus influenzae, n=2706). RESULTS: Among S. pneumoniae isolates,
      38.9% showed decreased susceptibility to penicillin (12.5% intermediate, 26.4%
      resistant) with marked geographical variability. The erythromycin resistance rate
      was 31.0% and highly correlated with penicillin resistance. The rate of
      fluoroquinolone resistance was 0.8%. Telithromycin was nearly uniformly active
      against S. pneumoniae (MIC(90) 0.5 mg/l). All isolates of S. pyogenes were
      penicillin-susceptible, 5.5% were resistant to erythromycin. Telithromycin
      minimum inhibitory concentrations (MICs) were lower than clindamycin and
      macrolide MICs against S. pyogenes (MIC(90) 0.03 mg/l versus 0.25 mg/l and 0.12
      mg/l, respectively). 28.3% of H. influenzae isolates produced beta-lactamase.
      Telithromycin activity versus H. influenzae was not affected by beta-lactamase
      production. CONCLUSIONS: The PROTEKT US study confirms the widespread prevalence
      of antimicrobial resistance among common bacterial respiratory pathogens in the
      US, and re-affirms the importance of continued surveillance to guide optimum
      empiric therapy for patients with Community-acquired respiratory tract infections
      (CARTIs). The new ketolide, telithromycin, maintained potent activity against
      study isolates in vitro and offers promise for the effective treatment of CARTIs.

PMID- 14667793
TI  - Differential induction of TNF-alpha and NOS2 by mitogen-activated protein kinase
      signaling pathways during Mycobacterium bovis infection.
AB  - The role of mitogen-activated protein kinase (MAPK) signaling pathways in the
      regulation of TNF-alpha and NOS2 production by human monocytes infected with
      Mycobacterium bovis BCG was examined. Inhibition studies showed that ERK1/2 and
      p38 MAPK activation were necessary for the monocyte response to M. bovis
      infection. Analysis of MAPK activation showed rapid phosphorylation of ERK1/2 and
      p38 in response to M. bovis BCG. Phosphorylation was not due to an autocrine
      effect of TNF-alpha secretion, since an anti-TNF-alpha antibody had no
      significant effect on the levels of p38 phosphorylation. The inhibitor PD98059
      significantly reduced M. bovis BCG-induced TNF-alpha production and almost
      completely abrogated phosphorylation of ERK1/2; in addition the potent MEK
      inhibitor U0126 also abrogated phosphorylation. In contrast, studies using
      inhibitors selective for ERK1/2 and p38 showed that p38 plays an essential role
      in the induction of NOS2, whereas the role of ERK1/2 was minor. These results
      suggest that ERK1/2 and p38 kinases differentially regulate the M. bovis BCG
      mediated induction of TNF-alpha and NOS2 in human monocytes.

PMID- 14667794
TI  - Comparative roles of macrophages and NK cells in the host innate resistance of
      mice to Mycobacterium fortuitum infection.
AB  - OBJECTIVES: Profiles of host innate resistance to Mycobacterium fortuitum (MFT)
      infection in mice and the roles of macrophages (Mphis) and NK cells in host
      resistance to MFT infection were studied. METHODS: MFT-infected mice with or
      without the treatments to reduce Mphis and NK cells were examined for survival
      and the bacterial loads in the kidneys during the course of infection. RESULTS: A
      unique profile of strain difference was found in the innate resistance of mice to
      MFT. A/J, C3H/He and DBA/2 mice were susceptible, while BALB/c, B10A and C57BL/6
      mice were resistant, in terms of survival after MFT infection. Such profiles of
      host resistance to MFT were essentially correlated with the ability of individual
      strain mice to prevent the bacterial growth in the early periods after infection.
      These profiles were different from the strain difference controlled by Bcg gene.
      Studies using carrageenan, anti-asialo GM1 antibody, and NK cell-deficient beige
      mice indicated the important roles of Mphis and NK cells in the host innate
      defense against MFT. CONCLUSIONS: These findings suggest that Bcg gene does not
      control the host resistance to MFT and that both Mphis and NK cells play crucial
      roles in the host innate resistance to MFT infection.

PMID- 14667795
TI  - Fever of unknown origin in Turkey: evaluation of 87 cases during a nine-year
      period of study.
AB  - OBJECTIVES: To investigate fever of unknown origin (FUO) in 87 patients. METHODS:
      We investigated 87 (61 male) patients with FUO using the criteria of Petersdorf
      and Beeson [Medicine 40 (1961) 1] hospitalized between January 1994 and August
      2002 at Cukurova University Hospital. RESULTS: The median age of the patients was
      38.5 years (range: 14-80 years). Eleven patients (12.6%) were over 65. The mean
      duration of hospitalization was 22.5+/-13 days. Infectious diseases were the most
      common causes of FUO. Tuberculosis (n=15, 17.2%), infective endocarditis (n=6),
      abdominal abscess (n=6), brucellosis (n=5), urinary tract infection (n=5),
      visceral leishmaniasis (n=4), salmonellosis (n=3), rhinocerebral mucormycosis
      (n=4), atypical pneumonia, cerebral toxoplasmosis, Cytomegalovirus infection or
      encephalitis were diagnosed in 51 (58.6%) patients. The second most common causes
      of FUO were collagen vascular diseases (n=16, 18.3%) determined as vasculitis
      syndrome, adult Still's disease (n=4), systemic lupus erythematosus, Behcet's
      disease, juvenile ankylosing spondylitis. Neoplasm was found in 12 (13.7%)
      patients; (non-Hodgkin lymphoma, Hodgkin lymphoma, chronic myeloid leukemia,
      gastrointestinal tract carcinoma, glioma). Miscellaneous diseases thyroiditis,
      granulomatous hepatitis were diagnosed in two (2.2%) patients. On admission, six
      patients (6.8%) were neutropenic. CONCLUSIONS: Infectious diseases, especially
      tuberculosis, were the leading diagnostic category of FUO in this study. Adult
      Still's disease was more common than expected. An aetiological diagnosis could
      not be reached in six (7%) patients who were followed for 1 year. Five of these
      patients completely recovered, and one patient died.

PMID- 14667796
TI  - Cerebral venous and dural sinus thrombosis in severe falciparum malaria.
AB  - Common causes of coma in falciparum malaria are cerebral malaria, hypoglycaemia
      and electrolyte disturbances. Focal deficits due to arterial infarcts may
      sometimes occur in children, but are rare in adults. Three adults with falciparum
      malaria who had fever, altered consciousness and focal neurological deficits (one
      of whom also had seizures) are being reported here. CT scan of the brain revealed
      haemorrhagic infarction of the cerebral cortex and subcortical white matter with
      surrounding oedema suggestive of venous infarction in all three patients. The
      diagnosis of cerebral venous thrombosis was missed in the first patient, and was
      detected only at autopsy. In the next two patients, superior sagittal sinus
      thrombosis was confirmed angiographically. Only one patient survived; the other
      two died of increased intracranial pressure. Two of the three patients also had
      Plasmodium vivax co-infection. A hypercoagulable state resulting from severe
      malaria may be responsible for this rare and potentially fatal complication.
      Cerebral malaria may be associated with raised intracranial pressure due to
      cerebral oedema. Cerebral venous thrombosis may worsen this and adversely affect
      outcome. This diagnosis should be suspected in patients with severe malaria who
      develop focal neurological deficits and confirmed by appropriate imaging;
      judicious use of local thrombolytic therapy may help improve outcome.

PMID- 14667797
TI  - Seroprevalence of Chlamydia pneumoniae infection in Taiwan.
AB  - OBJECTIVES: To survey the seroprevalence of Chlamydia pneumoniae (C. pneumoniae)
      infection in healthy subjects in Taiwan. MATERIALS AND METHODS: We used
      microimmunofluorescence antibody assay to survey the prevalence of antibodies to
      C. pneumoniae in 620 serum samples from healthy subjects aged 6 months to 86
      years in Taiwan. RESULTS: The mean prevalence (+/-SD) of IgG antibodies against
      C. pneumoniae at titer greater than or equal 1:16 was 55.8% (range 7.8-81.8%).
      The antibody prevalence was low in children under the age of 10 years (7.8%), and
      increased rapidly with age. Most individual acquired infection during the second
      and third decades of life with highest antibody prevalence reached up to 81.8% at
      fifth decade of life and remained high (70%) thereafter. CONCLUSIONS: Chlamydia
      pneumoniae infection is highly endemic in Taiwan. These data contribute to the
      understanding of asymptomatic infections with C. pneumoniae in general population
      and should serve as a basis for studies on the role of C. pneumoniae infections
      and their related diseases.

PMID- 14667798
TI  - Fungal peritonitis in patients on continuous ambulatory peritoneal dialysis: a
      single centre Indian experience.
AB  - BACKGROUND: Fungal peritonitis (FP) is a serious complication in patients on
      continuous ambulatory peritoneal dialysis (CAPD). We reviewed our FP cases to
      analyse the causative agents and possible risk factors in relation to FP and its
      outcome and mortality. METHODS: Records of all FP cases were reviewed. FP was
      diagnosed based on effluent cell count and positive fungal culture in suitable
      media. RESULTS: Between October 1993 and November 2001, 261 patients underwent
      CAPD. FP was detected in 28 patients, one episode in each patient (14.3% of the
      total peritonitis episodes). Candida species and dematiaceous fungi+/-Candida
      species were responsible for 89.3 and 10.7% of episodes, respectively. Patients
      with preceding bacterial peritonitis (BP) developed FP more frequently (25.6%)
      than de novo cases (2.9%) (P<0.0001) and lower proportion of them continued CAPD
      (8.6% vs. 60%; P=0.007). Mortality in patients having abdominal pain with and
      without fever, and catheter in situ was significantly higher than in those
      patients who did not have these risk factors (9/11 vs. 6/17, P=0.01; 13/17 vs.
      2/11, P=0.003; 6/6, vs. 9/22, P=0.01, respectively). CONCLUSIONS: Higher
      proportion of our patients had FP; preceding BP was a significant risk factor for
      development of FP and technique failure. Abdominal pain+/-fever in patients and
      catheter in situ were identified as risk factors associated with mortality.

PMID- 14667799
TI  - Uncommon mutation pattern of a hepatitis B virus isolate from genotype F
      infecting a patient with AIDS.
AB  - OBJECTIVE: To study the genomic variations of a hepatitis B virus (HBV) isolate
      in a patient coinfected with human immunodeficiency virus type 1 (HIV-1) who
      developed severe hepatitis and died of AIDS. METHODS: Two blood samples were
      collected, the first one during the asymptomatic phase of HIV-1 infection, and
      the other, 3 years later, few months before the death of the patient. Both
      samples were HBsAg and anti-HBe positive. Pre-S/S and precore-core genome regions
      were PCR amplified and analyzed. RESULTS: The HBV isolate belonged to genotype F,
      cluster IV. A number of unique amino acid substitutions were found in the surface
      antigen gene and the overlapping polymerase coding region of HBV genomes derived
      from both samples. However, these substitutions reflected natural variations
      rather than mutations of clinical significance. The precore stop codon mutation
      A(1896) was present in both genomes. Furthermore, the HBV genome derived from the
      second, but not first sample, showed two out-of-frame core interval deletions,
      one and 103 nucleotides in length, respectively. CONCLUSIONS: This is the first
      report of an HBV isolate from genotype F with core internal deletions. Our
      results suggest an association between specific core mutations and the severe
      hepatitis developed by the patient.

PMID- 14667800
TI  - TB and coeliac disease.
AB  - We report 2 cases of pulmonary tuberculosis, which did not respond to adequate
      therapy. Both these patients were later found to have coeliac disease, which led
      to malabsorption of the TB medications. On treating the coeliac disease with a
      gluten free diet, the patients responded to TB treatment.

PMID- 14667801
TI  - Fatal Scopulariopsis brevicaulis infection in a paediatric stem-cell transplant
      patient treated with voriconazole and caspofungin and a review of Scopulariopsis
      infections in immunocompromised patients.

PMID- 14667802
TI  - Antibiotics prescription in hospitalized patients at a Chinese University
      hospital.

PMID- 14667803
TI  - Genetic amplification of the transcriptional response to hypoxia as a novel means
      of identifying regulators of angiogenesis.
AB  - The cellular response to hypoxia involves the promotion of angiogenesis, leading
      to increased blood flow and oxygenation. The macrophage has been identified as an
      orchestrator of this response in several pathologies, through the release of
      angiogenic factors in response to hypoxia. We have produced the first
      comprehensive transcriptome analysis of hypoxic primary human macrophages with
      respect to the regulation of angiogenesis. There is a marked induction of genes
      encoding factors known to stimulate angiogenesis, rather than factors that
      inhibit this process. We show that overexpression of the transcription factor
      EPAS1 using a recombinant adenoviral vector amplifies the induction of genes
      encoding angiogenic proteins in response to hypoxia. This defines a new strategy
      for enhancing transcriptome and proteome analyses by overexpressing disease
      implicated genes using viral gene transfer methodologies.

PMID- 14667804
TI  - cDNA cloning, genomic structure, chromosomal mapping, and expression analysis of
      parotid secretory protein in pig.
AB  - A novel cDNA has been isolated from pig parotid glands by 3' and 5' rapid
      amplification of cDNA ends and designated parotid secretory protein (PSP). The
      open reading frame of this cDNA covers 714 bases, encoding 238 amino acids, which
      show 56% identity with human PSP at the level of the primary protein structure.
      The PSP genomic sequence comprises eight exons and seven introns, is
      approximately 22 kb in size, determined by sequencing, and maps to pig chromosome
      17q21-q23. RT-PCR, dot blot, and Northern blot analyses demonstrated that PSP is
      strongly expressed in parotid glands, but is not present in heart, liver, lung,
      kidney, muscle, or stomach. A search for functionally significant protein motifs
      revealed consensus sequences for casein kinase II phosphorylation and N
      myristoylation. We observed a unique amino acid sequence pattern consisting of
      the residues Leu-X(6)-Leu-X(6)-Leu-X(7)-Leu-X(6)-Leu-X(6)-Leu near the amino
      terminal portion of the protein, which is similar to the leucine zipper.

PMID- 14667805
TI  - Convergent evolution in primates and an insectivore.
AB  - The cardiovascular risk factor LPA has a puzzling distribution among mammals, its
      presence being limited to a subset of primates and a member of the insectivore
      lineage, the hedgehog. To explore the evolutionary history of LPA, we performed
      extensive genomic sequence comparisons of multiple species with and without an
      LPA gene product, such as human, baboon, hedgehog, lemur, and mouse. This
      analysis indicated that LPA arose independently in a subset of primates,
      including baboon and human, and an insectivore, the hedgehog, and was not simply
      lost by species lacking it. The similar structural domains shared by the hedgehog
      and primate LPA indicate that they were formed by a unique molecular mechanism
      involving the convergent evolution of paralogous genes in these distant species.

PMID- 14667806
TI  - Molecular cloning of nonsecreted endothelial cell-derived lipase isoforms.
AB  - To expand our knowledge of factors involved in lipid metabolism in the blood
      vessel wall, we have cloned unique molecular isoforms of endothelial cell-derived
      lipase (EDL) (HGMW-approved symbol/LIPG). One isoform encoded a truncated protein
      (EDL2a) lacking the first 80 amino acid residues of the previously characterized
      EDL1a isoform, including the signal peptide. A similar second clone (EDL2b) was
      identified that lacked not only the first 80 amino acids, but also a 74-amino
      acid region that encodes a portion of the lid domain. RT-PCR analysis confirmed
      expression of EDL2a/2b isoforms in several human tissues and cultured cells,
      including endothelial cells. Western blot and immunofluorescence studies using
      stable transfectants revealed that EDL2a and EDL2b were localized in the cytosol,
      while, EDL1a was secreted into the culture medium. Cell extracts of EDL2a/2b
      transfectants did not have triglyceride or phospholipase activity. Thus
      endothelial cells express three EDL isoforms, two of which remain intracellular
      and do not function as lipases.

PMID- 14667807
TI  - Identification of genes involved in estrogenic action in the human prostate using
      microarray analysis.
AB  - Estrogens have profound effects on the developing prostate and are suspected to
      contribute to the development of benign prostatic hyperplasia, but the mechanism
      by which this hormone elicits its regulatory function still remains largely
      unknown. Using complementary RNA microarrays comprising approximately 10,000
      oligonucleotide gene targets we compared differences in mRNA expression of
      estradiol-treated and untreated prostatic stromal cells in vitro. Based on a
      threshold of greater than twofold change, 228, 241, and 464 of the expressed
      genes were found to be regulated by estradiol after 10, 24, and 48 h of
      treatment, respectively. The secondary analysis of one estradiol-activated
      transcript, namely lipopolysaccharide-binding protein, and four estradiol
      repressed genes, namely ras homolog gene family member E (RhoE/Rnd3), ubiquitin
      thiolesterase, interleukin 6, and interleukin 8 (IL-8), by real-time quantitative
      PCR confirmed the results of the microarray analysis. Moreover, IL-8 and RhoE
      were found to be down-regulated by estradiol at the protein level as well. We
      identified a set of genes involved in a wide range of cellular functions that are
      potentially important for understanding the molecular basis of estradiol action
      in the prostate.

PMID- 14667808
TI  - Transcriptome analysis of early chondrogenesis in ATDC5 cells induced by bone
      morphogenetic protein 4.
AB  - We performed serial analysis of gene expression (SAGE) profiling in mouse
      chondrogenic ATDC5 cells before and 6 h after the onset of chondrogenesis induced
      by BMP4. A total of 43,656 SAGE tags (21,875 and 21,781 tags from the uninduced
      and induced libraries, respectively) were analyzed. Our analysis predicted that
      139 transcripts were differentially represented in the two libraries (p < 0.05),
      including 72 downregulated and 67 upregulated transcripts. Ninety-five of them
      matched single UniGene entries (77 known genes and 18 ESTs), while 12 tags
      corresponded to potentially novel genes. Surprisingly, many of these known genes
      have never been implicated in chondrogenic differentiation. Interestingly, we
      found that a significant fraction of these genes formed physical linkage groups.
      This suggests that the transcriptional control by BMP signaling is in part
      targeted to genes in certain chromosomal domains. Together, our results provide
      novel insights into molecular events regulated by BMP signaling in
      chondrogenesis.

PMID- 14667809
TI  - Distribution pattern of Notch3 mutations suggests a gain-of-function mechanism
      for CADASIL.
AB  - Mutations in Notch3 cause the syndrome CADASIL (cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy). The mechanism by
      which these mutations result in a CADASIL phenotype has been widely speculated
      upon. A first step toward understanding a disease mechanism is to learn whether
      the mutations result in the loss of Notch3 function, in particular, its role in
      signaling or in the gain of a novel function. Notch3 genomic sequences were
      analyzed for sites of conservation across species. We present here a
      bioinformatic analysis of the Notch paralogs and orthologs that suggest that
      CADASIL mutations result in a gain of function. This finding diminishes the
      likelihood that a Notch3 signaling deficit is responsible for the phenotype and
      increases the likelihood that CADASIL joins the growing list of neurological
      diseases with protein deposits due to misfolding and aggregation.

PMID- 14667810
TI  - Functional analysis of bacterial artificial chromosomes in mammalian cells: mouse
      Cdc6 is associated with the mitotic spindle apparatus.
AB  - Bacterial artificial chromosomes (BACs) provide a well-characterized resource for
      studying the functional organization of genes and other large chromosomal
      domains. To facilitate functional studies in cell cultures, we have developed a
      simple approach for generating stable cell lines with variable copy numbers of
      any BAC. Here we describe hamster cell lines with BAC transgenes that express
      mouse Cdc6 at levels that correlate with BAC copy number; show that mouse Cdc6 is
      regulated normally during the cell cycle, binds chromatin, and is degraded during
      apoptosis; and report a novel fraction of Cdc6 that associates with the spindle
      apparatus during mitosis. With RNA interference to assess genetic complementation
      by BAC alleles, this system will facilitate functional studies on large
      chromosomal domains at variable copy number in mammalian cell models.

PMID- 14667811
TI  - Evolutionary conservation of a 2-kb intronic sequence flanking a tissue-specific
      alternative exon in the PTBP2 gene.
AB  - nPTB is a member of the polypyrimidine tract-binding (PTB) protein family, which
      participates in alternative pre-mRNA processing. Tissue-specific splicing of exon
      10 in nPTB (HGMW-approved symbol PTBP2) may play an important role in regulating
      the functional activity of nPTB in neuronal versus nonneuronal cells. In this
      study, we found that 297 consecutive intronic nucleotides flanking this
      alternatively spliced exon 10 were identical between human, green monkey, mouse,
      rat, and pig, while 207 consecutive intronic nucleotides were identical between
      human and bird DNA. In addition, a 2-kb sequence spanning this intron region
      showed 85 and 70% conservation in mammal and bird DNA, respectively. Unexpected
      intergenic sequence conservation between human and mouse genomes has recently
      been identified. We have now identified intragenic (intronic) sequence
      conservation from mammals to birds. The striking conservation of this large
      segment of flanking intronic sequence suggests an important role in tissue
      specific splice site selection and may function in regulating the production of
      functional nPTB.

PMID- 14667812
TI  - A gene expressed exclusively in acute B lymphoblastic leukemias.
AB  - Representational difference analysis, a cDNA subtraction approach, was used to
      identify genes that are expressed in acute leukemia but not in normal
      hematological tissues. We isolated a cDNA fragment from a cell line derived from
      a B cell acute lymphoblastic leukemia bearing two Philadelphia chromosomes. The
      cDNA derives from an orphan gene that was named BLACE. BLACE is located in region
      7q36 and encodes a major 5.3-kb transcript and several alternatively spliced
      minor transcripts. Significant expression of BLACE was detected by RT-PCR and
      quantitative RT-PCR in bone marrow samples from B cell acute lymphoblastic
      leukemia patients. BLACE was not or was scarcely expressed in other types of
      hematological malignancies, in normal tissues, and in solid tumors.

PMID- 14667813
TI  - Gene expression in sheep skin and wool (hair).
AB  - We sequenced 2939 ESTs from fetal and adult sheep skin. Stages of gestation were
      picked to coincide with the major events in skin appendage (wool follicle)
      formation. Clustering analysis generated a nonredundant set of ESTs 2435 strong
      (83% nonredundant). Approximately 24% of these gave no hit to NCBI build 29 of
      the human genome, while 35% were tentatively classified by putative function
      based on BLASTX hits with a p(N) of <10(-4). In addition to bioinformatics
      analysis of our ESTs and gene mapping, we have generated a large EST spatial
      expression data set using in situ hybridization. One thousand one hundred forty
      two ESTs have been used for in situ localization; about 31% are from adult sheep
      skin, 39% from late gestation fetal sheep skin, and 30% from midgestation fetal
      sheep skin. These probes have been used in over 3000 hybridization experiments.
      In this report, we summarize the results of in situs on adult sheep skin.

PMID- 14667814
TI  - Gene structure and expression of the 5'-(CGG)(n)-3'-binding protein (CGGBP1).
AB  - The human nuclear 5'-(CGG)(n)-3'-binding protein (CGGBP1) influences the
      expression of the fragile X mental retardation (FMR1) gene by specifically
      interacting with the 5'-(CGG)(n>5)-3' repeat in its 5' untranslated region. Here,
      we show that CGGBP1 binds to 5'-(CGG)(n)-3' repeats with n>or=5 and to
      interrupted repeats. The genomic and mRNA organization of the human and murine
      CGGBP1 genes was studied and the human gene was mapped to chromosome 3p. Due to
      alternative polyadenylation, mRNAs of 1.2 and 4.5 kb are transcribed at varying
      ratios in human and murine cells and in embryonic, fetal, and adult tissues. The
      human and the murine genes, including promoters and large parts of the
      untranslated regions, are highly conserved. A sequence of 235 nucleotides 5'
      upstream of CGGBP1 is essential for promoter activity in transfection
      experiments. Complete in vitro methylation inactivates the promoter, which is
      unmethylated in human cells as shown by bisulfite genomic sequencing.

PMID- 14667816
TI  - Structural diversity and functional implications of the eukaryotic TDP gene
      family.
AB  - TDP-43 is an RNA-binding protein that functions in mammalian cells in
      transcriptional repression and exon skipping. The gene encoding TDP-43 (HGMW
      approved gene symbol TARDBP) is conserved in human, mouse, Drosophila
      melanogaster, and Caenorhabditis elegans. Sequence comparison of the coding
      regions of the TDP genes among the four taxa reveals an extraordinarily low rate
      of sequence divergence, suggesting that the TDP genes carry out essential
      functions in these organisms. With DNA transfection assay, we have established
      the importance of the glycine-rich domain for the exon-skipping activity of TDP
      43. Both human and mouse TDP genes belong to a gene family that also consists of
      a number of processed pseudogenes. Interestingly, combined database analysis and
      cDNA cloning have demonstrated that the primary transcript of the mammalian TDP
      genes undergoes alternative splicing to generate 11 mRNAs, including the one
      encoding TDP-43. Eight of the 11 splicing events involved the use of four each of
      the 5'-donor and 3'-acceptor sites, all of which reside within the last exon of
      the TDP-43 mRNA. The existence of multispliced isoforms of TDP-encoded proteins
      provides further support for the functional complexity of the eukaryotic TDP
      genes.

PMID- 14667815
TI  - Regulation of aldehyde reductase expression by STAF and CHOP.
AB  - Aldehyde reductase is involved in the reductive detoxification of reactive
      aldehydes that can modify cellular macromolecules. To analyze the mechanism of
      basal regulation of aldehyde reductase expression, we cloned the murine gene and
      adjacent regulatory region and compared it to the human gene. The mouse enzyme
      exhibits substrate specificity similar to that of the human enzyme, but with a 2
      fold higher catalytic efficiency. In contrast to the mouse gene, the human
      aldehyde reductase gene has two alternatively spliced transcripts. A fragment of
      57 bp is sufficient for 25% of human promoter activity and consists of two
      elements. The 3' element binds transcription factors of the Sp1 family. Gel-shift
      assays and chromatin immunoprecipitation as well as deletion/mutation analysis
      reveal that selenocysteine tRNA transcription activating factor (STAF) binds to
      the 5' element and drives constitutive expression of both mouse and human
      aldehyde reductase. Aldehyde reductase thus becomes the fourth protein-encoding
      gene regulated by STAF. The human, but not the mouse, promoter also binds C/EBP
      homologous protein (CHOP), which competes with STAF for the same binding site.
      Transfection of the human promoter into ethoxyquin-treated mouse 3T3 cells
      induces a 3.5-fold increase in promoter activity and a CHOP-C/EBP band appears on
      gel shifts performed with the 5' probe from the human aldehyde reductase
      promoter. Induction is attenuated in similar transfection studies of the mouse
      promoter. Mutation of the CHOP-binding site in the human promoter abolishes CHOP
      binding and significantly reduces ethoxyquin induction, suggesting that CHOP
      mediates stimulated expression in response to antioxidants in the human. This
      subtle difference in the human promoter suggests a further evolution of the
      promoter toward responsiveness to exogenous stress and/or toxins.

PMID- 14667817
TI  - A protein encoded by a member of the multicopy Ssty gene family located on the
      long arm of the mouse Y chromosome is expressed during sperm development.
AB  - Multicopy Y-chromosomal genes in human and mouse have been postulated to play a
      role in spermatogenesis. The mouse Y long arm (Yq) carries hundreds of supposedly
      intronless copies of Ssty, for which no protein has hitherto been identified;
      mice lacking Yq are sterile with grossly abnormal sperm. We have now identified
      an Ssty-encoded protein (Ssty1) that is expressed in spermatids. The protein is
      absent from spermatids of mice that lack Yq, but is not reduced in mice with a
      two-thirds reduction of Ssty copies, implying that most do not produce this
      protein. Furthermore, no protein was produced by a strongly transcribed
      intronless Ssty transgene, raising doubts as to the protein-encoding potential of
      these intronless genes. We have now identified an intron-containing copy that is
      also present in multiple copies on Yq. One or more intron-containing copies are
      retained in the Ssty-deficient mice and may be the source of the Ssty1 protein.

PMID- 14667818
TI  - Physical and linkage mapping of mammary-derived expressed sequence tags in
      cattle.
AB  - This study describes the physical and linkage mapping of 42 gene-associated
      markers developed from mammary gland-derived expressed sequence tags to the
      cattle genome. Of the markers, 25 were placed on the USDA reference linkage map
      and 37 were positioned on the Roslin 3000-rad radiation hybrid (RH) map, with 20
      assignments shared between the maps. Although no novel regions of conserved
      synteny between the cattle and the human genomes were identified, the coverage
      was extended for bovine chromosomes 3, 7, 15, and 29 compared with previously
      published comparative maps between human and bovine genomes. Overall, these data
      improve the resolution of the human-bovine comparative maps and will assist
      future efforts to integrate bovine RH and linkage map data.

PMID- 14667819
TI  - Analysis of a high-throughput yeast two-hybrid system and its use to predict the
      function of intracellular proteins encoded within the human MHC class III region.
AB  - High-throughput (HTP) protein-interaction assays, such as the yeast two-hybrid
      (Y2H) system, are enormously useful in predicting the functions of novel gene
      products. HTP-Y2H screens typically do not include all of the reconfirmation and
      specificity tests used in small-scale studies, but the effects of omitting these
      steps have not been assessed. We performed HTP-Y2H screens that included all
      standard controls, using the predicted intracellular proteins expressed from the
      human MHC class III region, a region of the genome associated with many
      autoimmune diseases. The 91 novel interactions identified provide insight into
      the potential functions of many MHC genes, including C6orf47, LSM2, NELF-E
      (RDBP), DOM3Z, STK19, PBX2, RNF5, UAP56 (BAT1), ATP6G2, LST1/f, BAT2, Scythe
      (BAT3), CSNK2B, BAT5, and CLIC1. Surprisingly, our results predict that 1/3 of
      the proteins may have a role in mRNA processing, which suggests clustering of
      functionally related genes within the human genome. Most importantly, our
      analysis shows that omitting standard controls in HTP-Y2H screens could
      significantly compromise data quality.

PMID- 14667820
TI  - Characterization of a new mRNA species from the human histamine N
      methyltransferase gene.
AB  - Histamine N-methyltransferase (HNMT), a cytosolic histamine-metabolizing enzyme,
      is the only known product of the 50-kb human HNMT. Here, a detailed investigation
      of HNMT products revealed the existence of a new brain mRNA product of HNMT. This
      species, named HNMT-Short (HNMT-S), encodes a 126-amino-acid protein. Northern
      blot analysis detected HNMT-S mRNA (1.0 kb) in placenta, but not in several other
      human tissues. In addition, unlike the known HNMT cDNA, HNMT-S cDNA did not
      result in histamine-methylating activity after transfection into COS-7 cells.
      These studies show that HNMT-S is a new mRNA species and putative protein product
      from HNMT. The physiological role of HNMT-S remains to be investigated.

PMID- 14667821
TI  - Assessment of the gene content of the chromosomal regions flanking bovine DGAT1.
AB  - As a first step towards verifying the candidate status of DGAT1 as the causal
      gene for milk fat percentage in cattle, we constructed a bovine BAC contig
      spanning 576 kb of the chromosomal region containing DGAT1. High content of NotI
      sites (21 within the contig) indicated that the region is gene-rich. Twenty-three
      genes neighboring DGAT1 were mapped, including two bovine cDNA sequences that
      have no orthologous sequences within the NCBI sequence databases. On average,
      2015 bp for each of the 23 neighboring genes were sequenced and entered into
      EMBL. Likewise, 10 new STS markers were established by BAC-end sequencing. Within
      the genes and STS markers, 55 polymorphisms were discovered. These will form the
      basis of future linkage disequilibrium studies to test whether any genes
      neighboring DGAT1 are associated with variation in milk fat percentage, thereby
      testing the candidate status of DGAT1.

PMID- 14667822
TI  - Fkbp8: novel isoforms, genomic organization, and characterization of a forebrain
      promoter in transgenic mice.
AB  - The immunophilin homolog FKBP8 has been implicated in the regulation of
      apoptosis. Here we show that the 38-kDa form of FKBP8 (FKBP38) derives from a
      truncated ORF. The extended FKBP8 ORFs are 46 and 44 kDa in mouse and 45 kDa in
      human. Although the genomic organization of mouse and human FKBP8 is
      evolutionarily conserved, additional first exons are encoded by the murine locus.
      A 4.4-kb murine Fkbp8 gene fragment, containing a GC-rich potential promoter,
      directed expression of a LacZ reporter gene to forebrain neurons in transgenic
      mice. Expression of the transgene was observed in CA1 pyramidal neurons of the
      hippocampus in transgenic mice from three lines. One transgenic founder mouse
      exhibited widespread forebrain expression of the LacZ transgene that resembles
      the pattern for the endogenous Fkbp8 gene. Thus promoter/enhancer elements for
      forebrain expression are located around the first exons of the mouse Fkbp8 gene.

PMID- 14667823
TI  - Function of the ubiquitin proteolytic pathway in the eye.
AB  - The ubiquitin pathway (UP) is involved in regulation of many essential cellular
      processes usually by the degradation of regulators of these processes. For
      example the UP is involved in regulation of cell cycle, proliferation,
      differentiation, organogenesis, development, and signal transduction in the lens
      and retina. A functional UP has also been documented in the cornea. Upon aging or
      exposure to stress there is an accumulation of damaged proteins, including
      ubiquitinated proteins, in the lens and retina. Some of these proteins may be
      cytotoxic. Thus, an active UP may be required to avoid such age and disease
      related accumulation of damaged proteins. In this review we will explain the
      biochemistry of the UP and we will document the most important studies regarding
      UP function in the lens, retina and cornea.

PMID- 14667824
TI  - Cell volume response to hyposmotic shock and elevated cAMP in bovine trabecular
      meshwork cells.
AB  - PURPOSE: Hyposmolar perfusion of intact trabecular meshwork (TM) induces a
      decrease in its hydraulic conductivity (Lp). However, exposure to agents that
      elevate intracellular cAMP in TM cells increases Lp. Since volume of TM cells
      could directly influence porosity of the TM and hence Lp, this study has
      investigated changes in volume in response to acute hyposmotic shock (i.e.
      regulatory volume decrease or RVD) and elevated cAMP in cultured TM cells.
      METHODS: Bovine trabecular meshwork cells (BTMC), grown on glass coverslips and
      loaded with the fluorescent dye MQAE, were used to measure rapid changes in cell
      volume using the principle of dynamic fluorescence quenching. Activation of
      volume-regulated anion channels (VRAC) was assessed by measuring volume-sensitive
      Cl(-) currents (I(Cl,swell)) in the whole cell configuration of the patch clamp
      technique and by determining the swelling-induced enhancement in I(-)
      permeability using the halide-sensitivity of MQAE. Expressions of ClC (chloride
      channels of the ClC gene family), P-glycoprotein (Pgp), and cystic fibrosis
      transmembrane regulator (CFTR) Cl(-) channels were examined by RT-PCR. Elevation
      of cAMP in response to forskolin was confirmed by determining the phosphorylation
      of cAMP response element-binding protein and activating transcription factor-1
      (CREB, ATF-1), which form the downstream targets of protein kinase A. RESULTS: As
      a response to hyposmotic shock, there was an acute increase in cell volume but
      there was no robust RVD. Patch clamp experiments showed activation of a
      characteristic Cl(-) current in response to cell swelling. This Cl(-) current was
      inhibited by NPPB (100microM) and fluoxetine (50microM), both of which are known
      blockers of VRAC. Experiments, which used the halide-sensitivity of MQAE, also
      indicated a 9-fold increase in I(-) influx upon cell swelling (8.9+/-4.6; n=9),
      consistent with activation of a VRAC-like Cl(-) current. To examine whether RVD
      is limited by K(+) conductance, the swollen cells were exposed to gramicidin,
      which is known to induce cation channel activity. Such a maneuver led to
      secondary swelling with [Na(+)](o)=140mM but a rapid shrinkage [Na(+)](o)=8mM
      indicating that the RVD is limited by cationic conductance necessary for K(+)
      efflux. Exposure to forskolin, which resulted in CREB and ATF-1 phosphorylation,
      caused a reversible decrease in cell volume (14.5+/-5%; n=20) under isosmotic and
      hyposmotic conditions. RT-PCR analysis confirmed expression of ClC-2, ClC-5, and
      Pgp Cl(-) channels in bovine TM cells. However, ClC-3 and CFTR were not
      expressed. CONCLUSIONS: TM cells respond to acute hyposmotic shock in an
      osmometric manner, but their RVD is limited by K(+) conductance. The lack of CFTR
      expression and decrease in cell volume in response to forskolin concomitant with
      hyposmolarity suggest that elevated cAMP activates a K(+) conductance. Thus, the
      altered resistance to aqueous outflow in response to hyposmotic perfusion of the
      TM and elevated cAMP may be attributed to persistent cell swelling and cell
      shrinkage, respectively.

PMID- 14667826
TI  - Radius of curvature and asphericity of the anterior and posterior surface of
      human cadaver crystalline lenses.
AB  - The purpose of this study was to measure the shape of the anterior and posterior
      surface of human cadaver lenses in situ using a corneal topography system.
      Measurements were performed on 13 pairs of eyes using the PAR Corneal Topography
      System (PAR-CTS). The age of the donors ranged from 46 to 93 years, with an
      average age of 76.4 years. Anterior lens topography was measured after excision
      of the cornea and iris. Posterior lens topography was measured after sectioning
      the posterior segment and adherent vitreous. The PAR-CTS files providing raw
      surface height were exported for analysis. In each surface, 18 meridians
      separated by 10 degrees were fitted using conic sections to obtain values of the
      apical radius of curvature (R) and shape factor (p). The average apical radius of
      curvature and asphericity were R=10.15+/-1.39mm and p=4.27+/-1.39 for the
      anterior surface and R=-6.25+/-0.79mm and p=-0.64+/-1.85 for the posterior
      surface. A significant variation of the radius of curvature and shape factor as a
      function of the meridian angle (lens astigmatism) was found in some lenses.
      Contrary to previous findings, the anterior lens surface was found to steepen
      toward the periphery.

PMID- 14667825
TI  - Role of Gas6/Axl signaling in lens epithelial cell proliferation and survival.
AB  - Axl is a receptor tyrosine kinase that is activated by Gas6, a growth factor that
      belongs to the vitamin K-dependent protein family. Although Gas6 binding to Axl
      has been shown to transmit mitogenic and/or antiapoptotic signals to a variety of
      cell types, the role of the Axl-Gas6 system in normal and pathological lens
      biology is not known. We demonstrate for the first time that Axl protein is
      expressed in normal rat and bovine lens and that its ligand, Gas6, is present in
      bovine aqueous humor. In addition, we have detected tyrosine-phosphorylated Axl
      in normal rat and bovine lens epithelial tissues. We further show that human
      recombinant Gas6 is able to act as a growth factor in cultured human lens
      epithelial cells by activating Axl and then the AKT signaling pathway. Gas6
      mediates a survival and anti-apoptotic response in cultured human lens epithelial
      cells subjected to serum-starvation (48-72hr), or treated with transforming
      growth factor beta1 (5 ng ml(-1), 48hr) or tumor necrosis alpha (100 ng ml(-1),
      48hr), as demonstrated by increased number of viable cells, and decreased DNA
      condensation or caspase-3 activity. In contrast, Gas6 is not able to block
      apoptosis induced by staurosporin (1microM, 5-24hr) in human lens epithelial
      cells. Taken together, these data suggest that the Gas6/Axl signaling plays an
      important role in the control of lens epithelial cell growth and survival and
      hence in the maintenance of lens homeostasis.

PMID- 14667827
TI  - Short-term study of retinal pigment epithelium sheet transplants onto Bruch's
      membrane.
AB  - The purpose of this study is to investigate the survival and behaviour of retinal
      pigment epithelium sheets transplanted onto hydraulically debrided Bruch's
      membrane. Uncultured retinal pigment epithelium sheets obtained from male cats
      and sandwiched between two gelatin sheets were transplanted onto the tapetal area
      of female cats after native retinal pigment epithelium was debrided. For
      controls, the gelatin carrier was transplanted after debridement. Each transplant
      or control specimen was analyzed histologically and immunohistochemically.
      Transplanted male retinal pigment epithelial cells were identified by in situ
      labelling of the cat Y chromosome. Over half of the transplants appeared as
      retinal pigment epithelium multilayers in the subretinal space. Retinal pigment
      epithelium pigment dispersion into the subretinal space was seen in most of the
      transplants, and retinal pigment epithelium pigment infiltration into the neural
      retina was seen in all 7-day survival transplants. A few condensed darkly stained
      retinal pigment epithelium nuclei and Terminal Transferase dUTP Nick End
      Labelling-positive retinal pigment epithelium cells were observed in all
      transplants. Cellular retinaldehyde-binding protein was present up to day-7 in
      most transplanted RPE cells. In both transplant and control specimens, the
      antibody against the Ki-67 nuclear antigen labelled a few retinal pigment
      epithelium cells at day-3. Terminal Transferase dUTP Nick End Labelling-positive
      outer nuclear layer nuclei were most frequently observed at day-1 but were much
      less frequent at day-3 in both transplants and controls. The survival and
      effectiveness of retinal pigment epithelium sheet transplants appeared similar to
      the retinal pigment epithelium microaggregates transplants conducted previously
      in this model.

PMID- 14667828
TI  - 17Beta-estradiol confers a protective effect against transforming growth factor
      beta2-induced cataracts in female but not male lenses.
AB  - Transforming growth factor-beta2 (TGF-beta2) induces anterior subcapsular
      cataracts, with a marked increase in cytoskeletal and extracellular matrix
      proteins, such as alpha-smooth muscle actin (alphaSMA). It has been shown that
      17beta-estradiol (E2) can prevent TGF-beta2-induced cataracts in lenses from
      ovariectomized female rats. The purpose of the current study was to extend this
      finding by testing whether E2 can prevent TGF-beta2-induced cataracts and inhibit
      the induction of alphaSMA gene expression in normal male and normal, non
      ovariectomized female rats.Sex-specific differences were observed in 17-week-old
      rat lenses incubated in 0.15 ng ml(-1) TGF-beta2 and in 10(-8)M E2 plus TGF
      beta2. TGF-beta2 induced approximately twice as many anterior subcapsular plaques
      and 1.5 times the level of alphaSMA transcripts in male lenses compared to female
      lenses. Notably, E2 inhibited plaque formation and the induction of alphaSMA
      transcripts in female rat lenses but not in male rat lenses. E2 also inhibited
      the induction of alphaSMA in TGF-beta2-incubated lenses from ovariectomized
      female rats.E2 prevented lens opacification and the induction of alphaSMA gene
      expression in female, but not male, lenses. This sex-specific difference may have
      implications for studies on the therapeutic use of estradiol for treatment of
      secondary cataract.

PMID- 14667829
TI  - Distribution of caveolin-1 in bovine lens and redistribution in cultured bovine
      lens epithelial cells upon confluence.
AB  - The distribution of caveolin-1 in the lens and lens epithelial cells was
      determined to assess possible roles in cholesterol trafficking, cell to cell
      communication and signal transduction. Bovine lenses and cultured bovine lens
      epithelial cells (BLEC) were divided into subcellular fractions and the
      distribution of proteins recognized by three different caveolin-1 antibodies
      determined. The immunolocalization of caveolin-1 in the lens epithelium and in
      subconfluent and confluent cultured BLEC was probed by fluorescence microscopy
      and laser scanning confocal microscopy. EGF induced phosphorylation of caveolin-1
      was detected by Western blotting with an anti-phosphotyrosine antibody to
      immunoprecipitated caveolin-1 from BLEC and human cancer cells. Monomeric
      caveolin-1 of about 26 kDa was detected in the epithelial cell membrane of
      cultured BLEC and fresh epithelia and in the plasma membrane fraction of lens
      cortical fiber cells. Caveolin-1 of cultured BLEC redistributed from the
      cytoplasm to plasma membrane as the cells proceeded from subconfluent to
      confluent states. The apparent abundance of caveolin-1 in cortical fiber cell
      plasma membrane is consistent with possible roles in distribution of lens
      membrane cholesterol and membrane structure. The presence of caveolin-1 in the
      plasma membrane of epithelial cells at - but not before - confluency is
      consistent with a role of caveolin-1 in cell to cell communications. EGF
      stimulated phosphorylation of caveolin-1 in human A431 cells but not lens cells.

PMID- 14667830
TI  - Inter-ocular and inter-session reliability of the electroretinogram photopic
      negative response (PhNR) in non-human primates.
AB  - PURPOSE: To assess the inter-ocular and inter-session reliability for a range of
      parameters derived from the photopic electroretinogram (ERG) in a group of normal
      non-human primates. METHODS: Inter-ocular differences for photopic ERGs were
      assessed in a group of normal anesthetized adult rhesus monkeys (Macaca mulatta,
      n=29); inter-session reliability was assessed for 23 eyes of 23 animals tested 3
      months later. Signals were acquired using Burian-Allen contact lens electrodes,
      whereby the contralateral cornea served as a reference. Photopic ERGs were
      elicited using red Ganzfeld flashes (-0.5-0.67 log photopic cd.sm(-2)) on a rod
      suppressing blue-background (30 scotopic cdm(-2)). Measurement reliability was
      established for a-wave, b-wave, photopic negative response (PhNR) and oscillatory
      potential (OP) amplitudes, as well as for their implicit times, by calculation of
      the 95% limits-of-agreement (LOA) and the coefficient-of-variation (COV) for each
      parameter. RESULTS: OP and a-wave amplitudes increased with intensity up to 0.67
      log photopic cd.sm(-2), following a typical saturating function, whereas b-wave
      and PhNR amplitudes both declined above 0.42 log photopic cd.sm(-2). Inter
      session variability was greater than inter-ocular variability. The inter-session
      COVs for PhNR amplitude (10-20%) were similar to the other photopic ERG
      components (a-wave: 12-17%, b-wave: 12-17%, OPs: 13-19%). Inter-session LOAs were
      also similar across components, but on average, were smallest for responses to
      moderate intensities (0.0-0.42 log photopic cd.sm(-2)). CONCLUSION: In non-human
      primates, the 95% LOA for inter-session measurements of the photopic ERG a-wave,
      b-wave, OPs and PhNR are all similar. Inner-retinal damage may best be measured
      using the PhNR amplitude for moderately bright stimulus intensities. B-wave and
      PhNR amplitudes for brighter flashes are smaller and more variable. The ratio of
      PhNR:b-wave amplitudes manifests smaller variability and may therefore be useful
      for detection of selective PhNR loss.

PMID- 14667831
TI  - Rabbit retinal ganglion cell survival after optic nerve section and its effect on
      the inner plexiform layer.
AB  - Structural modifications of the inner retina were studied after optic nerve
      section (ONS) in the rabbit. Retinal ganglion cells (RGC) were labelled by
      injection of Fast Blue into the optic nerve, and counted under fluorescent light
      in control retina and retina 7, 14, 21 and 26 days post-axotomy. Studies on
      retinal cross-sections were also performed. For this purpose, retinal sections
      were stained with haematoxylin-eosin and immunohystochemistry for alpha1 and
      beta2/beta3 sub-units of the GABA(A) receptors. One week after axotomy, there was
      no significant loss in the number of ganglion cells with respect to control
      counts (1086+/-173cellsmm(-2) in the visual streak and 119+/-46cellsmm(-2) in the
      periphery, mean+/-SD, n=5). At 14 days post-axotomy, 271+/-46cellsmm(-2) remained
      in the visual streak and 33+/-6cellsmm(-2) in the periphery, corresponding to a
      mean survival of 27%. The number of ganglion cells decreased further on the
      following days, reaching 7.54% 1 month after ONS. A significant reduction in the
      thickness of the inner plexiform and ganglion cell layers was also observed in
      retinal cross-sections. Immunocytochemical studies show a remarkable
      disorganization of the layer stratification in the inner plexiform layer (IPL).
      We conclude that after ONS, RGC death occurs mainly between 7 and 14 days post
      axotomy and a progressive death up to 26 days, causing a decrease in the
      thickness of the IPL and subsequent disorganization of its layers.

PMID- 14667832
TI  - Effect of nucleotide P2Y2 receptor agonists on outward active transport of
      fluorescein across normal blood-retina barrier in rabbit.
AB  - BACKGROUND: To evaluate the effect of nucleotide P2Y(2) receptor agonists INS542
      and uridine 5'-triphosphate (UTP) on the outward active transport of fluorescein
      across rabbit blood-retina barrier (BRB) in vivo. METHODS: Injection (0.1 ml) of
      INS542 (0.1 or 1mM), phosphate buffered solution, or UTP (1 or 10mM) was made in
      Dutch-belted rabbits. Differential vitreous fluorophotometry (DVF) was performed
      3hr later and the fluorescein (F)/fluorescein monoglucuronide (FG) ratio was then
      calculated. F/FG ratios are inversely proportional to outward active transport of
      F across BRB at the level of the retinal pigment epithelium (RPE). In another set
      of experiments, the effect of 0.1 ml vitreous injection of INS542 (1mM) on F/FG
      ratios was evaluated at different time points ranging from 0.5 to 48hr before
      conducting DVF. RESULTS: F/FG ratios obtained 3hr after intravitreal injection
      were as follows (mean+/-standard error): 0.49+/-0.14 (0.1mM INS542), 0.19+/-0.04
      (1mM INS542), 0.48+/-0.09 (PBS), 0.40+/-0.08 (1mM UTP) and 0.36+/-0.05 (10mM
      UTP). The F/FG ratio for 1mM INS542 was significantly lower than in the other
      groups (P<0.05). In the time course experiments, a significant decrease in the
      F/FG ratios was observed between 1 and 12hr following administration of INS542
      when compared with F/FG ratios obtained in the contralateral (untreated) eye.
      CONCLUSION: Intravitreal administration of INS542 (but not UTP) enhances outward
      active transport of F across RPE in intact rabbit eye, indicating that activation
      of P2Y(2) receptors in vivo directly stimulates RPE active transport.

PMID- 14667833
TI  - Bfsp2 mutation found in mouse 129 strains causes the loss of CP49 and induces
      vimentin-dependent changes in the lens fibre cell cytoskeleton.
AB  - Here we report the first natural mutation in the mouse Bfsp2 gene.
      Characterisation of mouse Bfsp2 in the 129X1/SvJ revealed a mutation that deleted
      the acceptor site of exon 2. This results in exon 1 being erroneously spliced to
      exon 3 causing a frameshift in the reading frame and the introduction of a stop
      codon at position 2 of exon 3 in the Bfsp2 transcript. RT-PCR studies of lens RNA
      isolated from 129S1/SvImJ, 129S2/SvPas and 129S4/SvJae strains confirmed the
      presence of this mutation in these diverse 129 strains and similar mutations were
      found in both CBA and 101 strains, but not in C3H or C57BL/6J mouse strains. This
      mutation is predicted to result in a severely truncated protein product called
      CP49, comprising essentially only exon 1, but polyclonal antibodies to CP49
      failed to detect either full length or fragments of CP49 in extracts made from
      either 129S1/SvImJ or 129S4/SvJae suggesting that these 129 strains lack CP49
      protein. Like the knockout of Bfsp2 reported recently, filensin protein levels
      and its proteolytic processing were altered also in the 129S1/SvImJ and
      129S4/SvJae strains compared to C57BL/6J. Electron microscopy of the lens
      cytoskeleton from 129S2/SvPas revealed similar morphological changes in the
      cytoskeleton as compared to the CP49 knockout, with beaded and intermediate
      filaments being apparently replaced by poorly defined filament-like material.
      Vimentin was a key component of this residual material as shown by immunoelectron
      microscopy and by the generation of a CP49/vimentin double knockout mouse. This
      report of a natural mutation in Bfsp2 in the 129 and other mouse strains also has
      important implications for lens studies that have used the 129X1/SvJ strain in
      knockout strategies.

PMID- 14667834
TI  - Activation of ERK1/2 MAP kinase pathway induces tight junction disruption in
      human corneal epithelial cells.
AB  - Activation of protein kinase C (PKC) by exposure of cultured human corneal
      epithelial cells to phorbol 12-myristate 13-acetate (PMA) resulted in an increase
      in paracellular permeability as evidenced by a decrease in transepithelial
      electrical resistance (TER). A change in the membrane distribution of the tight
      junction protein ZO-1 was also observed in the PMA-treated cells. In contrast,
      when the cells were treated with PMA in the presence of PD98059, a specific
      inhibitor of mitogen-activated protein kinase (MAPK) kinase, all barrier
      characteristics were preserved, suggesting that PKC induces tight junction
      disruption through the activation of MAPK. The role of this signaling pathway in
      the regulation of epithelial permeability was further elucidated by the use of
      corneal epithelial-derived cell lines expressing constitutively activated (ca) or
      dominant-negative (dn) mutants of MAPK kinase-1 (MEK1). Transfectants of caMEK1,
      when compared to parental cells, had higher levels of phosphorylated
      extracellular regulated protein kinase (ERK), altered distribution of ZO-1 and
      occludin, and much reduced TER. On the other hand, dnMEK1 transfectants had lower
      but detectable levels of ERK phosphorylation, more flattened morphology, and,
      most importantly, significantly higher TER when compared to parental cells. Our
      study demonstrates that activation of PKC causes the disruption of tight
      junctions through activation of MAP kinase and that the MAP kinase signaling
      pathway plays a key role in the regulation of epithelial cell morphology and
      barrier function in the cornea.

PMID- 14667835
TI  - Functional and structural reversibility of H-7 effects on the conventional
      aqueous outflow pathway in monkeys.
AB  - To determine the mechanism of H-7-induced outflow resistance decrease, the
      reversibility of H-7 effects on outflow pathway was studied physiologically and
      morphologically in live monkey eyes. Total outflow facility was measured by two
      level constant pressure perfusion before (baseline measurement) and after (post
      drug measurement) anterior chamber (AC) exchange with 300microM H-7 or vehicle in
      opposite eyes of eight monkeys. H-7 was then removed by AC exchange with drug
      free vehicle in both eyes, followed by a 2.5hr waiting period, after which
      outflow facility was measured again with (Group 2; n=4) or without (Group 1; n=4)
      another preceding drug-free AC exchange. For morphological study, five monkeys
      were initially perfused similarly to Group 1 in physiology, but the facility
      measurement beginning 2.5hr after drug removal was either omitted or replaced by
      gold solution infusion. Following baseline measurement, two of the five monkeys
      received H-7 or vehicle in opposite eyes, while three monkeys received H-7 in
      both eyes 2.5hr apart, contributing one H-7-treated 'recovery' eye and one H-7
      treated 'acute' eye. After perfusion, both eyes of all five monkeys were studied
      by light and electron microscopy. Outflow facility during post-drug measurement
      in the H-7-treated eye was significantly increased by two-fold. However, the
      facility increase was reduced when measured beginning 2.5hr after drug removal,
      with the reduction being greater in Group 1. 'Recovered' outflow facility after
      drug removal gradually increased again under continuous AC infusion with drug
      free vehicle. Morphologically, major changes in and around Schlemm's canal (SC)
      in the H-7-treated 'acute' eye included protrusion of the entire inner wall (IW)
      into SC, relaxation of the IW cells and reorganization of the IW cytoskeleton.
      The changes in IW cells and juxtacanalicular region of the H-7-treated 'recovery'
      eye were non-uniform, with areas resembling the vehicle-treated eye ('contracted
      areas') and areas resembling the H-7-treated 'acute' eye ('relaxed areas'). The
      average junction-to-junction distances in the IW cells of the H-7-treated
      'recovery' eye were intermediate between the vehicle-treated eye and the H-7
      treated 'acute' eye. In conclusion, H-7's effect on outflow facility seems
      reversible, but AC exchange or continuous infusion with drug-free vehicle can re
      elevate the 'recovered' outflow facility. Major morphological changes in the TM
      immediately after H-7 include IW protrusion, cellular relaxation and cytoskeleton
      reorganization. The decrease in 'relaxed areas' in the TM, in conjunction with
      the reversed outflow facility, 2.5hr after drug removal suggests that cellular
      relaxation in the TM is the structural basis for H-7-induced increase in outflow
      facility.

PMID- 14667836
TI  - Dietary caloric restriction may delay the development of cataract by attenuating
      the oxidative stress in the lenses of Brown Norway rats.
AB  - Dietary caloric restriction (CR) is the only experimental intervention that can
      reliably retard the development of cataract in a normal animal model. Here we
      have studied the possible mechanisms by which CR retards the age-related
      degeneration of the lens of Brown Norway rats. We have found that CR slowed
      protein insolubilization and blunted declines of the total soluble thiols,
      protein thiols, reduced glutathione and ascorbic acid levels in the lenses of old
      BN rats. From the lens protein point of view, the development of cataract in rat
      lenses has 3 stages: (1) the precipitation of gamma-crystallin, (2) the
      insolubilization of beta-crystallin, and (3) the final precipitation of alpha
      crystallin which was saturated with other denatured lens proteins. A similar
      sequence is also observed when the lens proteins are subjected to oxidative
      stress in vitro. These data are the first to suggest that CR may retard the age
      related degeneration of the lens by attenuating the oxidative stress in the lens.
      Since oxidative stress is likely a main cause of human cataract, CR intervention
      may be relevant to humans as well.

PMID- 14667838
TI  - The RGD story: a personal account.

PMID- 14667839
TI  - An X-ray scattering investigation of corneal structure in keratocan-deficient
      mice.
AB  - The transparency of the cornea has been closely linked with the characteristic
      size and arrangement of its constituent collagen fibrils. This arrangement, in
      turn, is thought to depend on interactions with intervening matrix proteoglycans.
      The purpose of this investigation was to examine fibrillar collagen organisation
      in the corneas of mice homozygous for a null mutation in keratocan, a keratan
      sulfate-containing proteoglycan. Low-angle synchrotron X-ray scattering
      techniques were used. We found that keratocan-deficient mice had corneal collagen
      fibrils with significantly larger diameters than those in wild-type littermates.
      Furthermore, there was an increase in the centre-to-centre spacing of the
      collagen fibrils that was accompanied by a decrease in nearest-neighbour
      fibrillar order. We hypothesise that a lack of keratocan might lower the number
      of keratan sulfate proteoglycans that associate with collagen, leading to
      alterations in their diameters and spatial arrangements. Alternatively, it might
      change the osmotic balance between the inside and outside of fibrils, causing
      them to swell and move further apart.

PMID- 14667840
TI  - ECM gene expression correlates with in vitro tissue growth and development in
      fibrin gel remodeled by neonatal smooth muscle cells.
AB  - A tissue growth and development process occurred in neonatal SMC-fibrin gel
      constructs when cultured in DMEM supplemented with TGF-beta1 and insulin over a 5
      week period. These constructs may thus serve as the basis for cardiovascular
      tissue replacements and future models of cardiovascular tissue growth, repair and
      regeneration. Following fibrin gel contraction during week 1, peak rates of SMC
      proliferation, collagen production and tropoelastin production occurred between
      weeks 1-4. Organized, cross-linked collagen and elastic fibers replaced the
      degrading fibrin over weeks 3-5 and were manifested as increased mechanical
      strength. The peak rate of SMC proliferation (weeks 1-2) preceded that for
      maximum collagen production (weeks 2-4), which was consistent with the 3 week
      time point of maximum expression of collagen type I and III from qRT-PCR.
      Insoluble elastin quantification revealed that the majority of elastic fibers
      were produced by week 4, which was also consistent with the qRT-PCR data showing
      a dramatic down-regulation of tropoelastin expression by week 4, indicating
      elastogenesis occurred during the early stages of tissue growth and development.
      There was a strong up-regulation of lysyl oxidase expression during weeks 1-3
      with a peak in expression at week 3, correlating with the phases of collagen and
      tropoelastin production. An increase in MMP-2 expression over weeks 1-5 suggested
      an increase in ECM remodeling as the tissue developed. Mechanical strength
      doubled over weeks 4-5 when production of collagen and elastic fibers and
      expression of lysyl oxidase were subsiding. This may have been due in part to the
      more organized collagen fibrils evident from the histological sections in weeks 3
      5.

PMID- 14667841
TI  - Multidrug resistance protein-6 (MRP6) in human dermal fibroblasts. Comparison
      between cells from normal subjects and from Pseudoxanthoma elasticum patients.
AB  - Multidrug resistance protein-6 (MRP6) is a membrane transporter whose deficiency
      leads to the connective tissue disorder Pseudoxanthoma elasticum (PXE). In vitro
      dermal fibroblasts from normal and PXE subjects, homozygous for the R1141X
      mutation, were compared for their ability to accumulate and to release
      fluorescent calcein, in the absence and in the presence of inhibitors and
      competitors of the MDR-multidrug resistance protein (MRP) systems, such as 3-(3
      (2-(7-choro-2 quinolinyl) ethenyl)phenyl ((3-dimethyl amino-3-oxo-propyl)thio)
      methyl) propanoic acid (MK571), verapamil (VPL), vinblastine (VBL), chlorambucil
      (CHB), benzbromarone (BNZ) and indomethacin (IDM). In the absence of chemicals,
      calcein accumulation was significantly higher and the release significantly
      slower in PXE cells compared to controls. VBL and CHB reduced calcein release in
      both cell strains, without affecting the differences between PXE and control
      fibroblasts. VPL, BNZ and IDM consistently delayed calcein release from both
      control and PXE cells; moreover, they abolished the differences between normal
      and MRP6-deficient fibroblasts observed in the absence of chemicals. These
      findings suggest that VPL, BNZ and IDM interfere with MRP6-dependent calcein
      extrusion in in vitro human normal fibroblasts. Interestingly, MK571 almost
      completely abolished calcein release from PXE cells, whereas it induced a strong
      but less complete inhibition in control fibroblasts, suggesting that MRP6 is not
      inhibited by MK571. Data show that MRP6 is active in human fibroblasts, and that
      its sensitivity to inhibitors and competitors of MDR-MRPs' membrane transporters
      is different from that of other translocators, namely, MRP1. It could be
      suggested that MRP1 and MRP6 transport different physiological substances and
      that MRP6 deficiency cannot be overcome by other membrane transporters, at least
      in fibroblasts. These data further support the hypothesis that MRP6 deficiency
      may be relevant for fibroblast metabolism and responsible for the metabolic
      alterations of these cells at the basis of connective tissue clinical
      manifestations of PXE.

PMID- 14667842
TI  - ADAMTSL-3/punctin-2, a novel glycoprotein in extracellular matrix related to the
      ADAMTS family of metalloproteases.
AB  - The complete primary structure of ADAMTSL-3/punctin-2, a novel member of the
      family designated ADAMTSL (a disintegrin-like and metalloprotease domain with
      thrombospondin type I motifs-like), was determined by cDNA cloning from a human
      placenta library. The predicted open reading frame encodes a protein of 1690
      amino acids that has considerable similarity to ADAMTSL-1/punctin-1. These multi
      domain proteins lack both a protease domain and a disintegrin-like domain but are
      remarkably similar in their domain organization to the ADAMTS proteases, hence
      the name ADAMTS-like. Punctin-2 contains thrombospondin type 1 repeats (TSRs), a
      cysteine-rich domain and a cysteine-free spacer domain in the precise order in
      which they occur in the ADAMTS proteases. However, the number and organization of
      the TSRs in punctin-2 is unique with respect to the ADAMTS proteases. Punctin-2
      contains 13 TSRs arranged in two arrays separated by a region containing three
      immunoglobulin-like repeats. Northern blot analysis of RNA from human adult
      tissues demonstrated that ADAMTSL3 is widely expressed, with highest expression
      in liver, kidney, heart and skeletal muscle, whereas it is expressed at low
      levels in mouse embryos. We characterized two punctin-2 polyclonal antisera.
      Using these and a monoclonal antibody to a C-terminal myc tag, we show that in
      transfected COS-7 cells, punctin-2 is expressed as a 210-kDa glycoprotein that is
      located in the extracellular matrix. The domain structure of punctin-2 and its
      matrix localization suggest that it might play a role in cell-matrix interactions
      or in assembly of specific extracellular matrices.

PMID- 14667844
TI  - Monotreme biology.

PMID- 14667843
TI  - Molecular cloning, genomic organization and developmental expression of the
      Xenopus laevis hyaluronan synthase 3.
AB  - The content of hyaluronan (HA), a polymer of the extracellular matrix involved in
      a variety of physiological and pathological processes, depends on the activity of
      synthetic (HAS) and degrading enzymes. Since HA is also involved in
      embryogenesis, we have used Xenopus as a model organism because information is
      available for HAS1 and HAS2, but not for HAS3. We report the sequence of xlHAS3
      mRNA, its genomic organization and its expression in adult tissues as well as
      during embryonic development. Interestingly, evidence from in situ hybridization
      indicates that xlHAS3 expression is restricted to the developing inner ear and
      cement gland. In addition, we have correlated the expression pattern of the
      enzymes involved in HA metabolism with the HA content during development.

PMID- 14667845
TI  - Diving behaviour, dive cycles and aerobic dive limit in the platypus
      Ornithorhynchus anatinus.
AB  - We investigated the diving behaviour, the time allocation of the dive cycle and
      the behavioural aerobic dive limit (ADL) of platypuses (Ornithorhynchus anatinus)
      living at a sub-alpine Tasmanian lake. Individual platypuses were equipped with
      combined data logger-transmitter packages measuring dive depth. Mean dive
      duration was 31.3 s with 72% of all dives lasting between 18 and 40 s. Mean
      surface duration was 10.1 s. Mean dive depth was 1.28 m with a maximum of 8.77 m.
      Platypuses performed up to 1600 dives per foraging trip with a mean of 75 dives
      per hour. ADL was estimated by consideration of post-dive surface intervals vs.
      dive durations. Only 15% of all dives were found to exceed the estimated ADL of
      40 s, indicating mainly aerobic diving in the species. Foraging platypuses
      followed a model of optimised recovery time, the optimal breathing theory. Total
      bottom duration or total foraging duration per day is proposed as a useful
      indicator of foraging efficiency and hence habitat quality in the species.

PMID- 14667846
TI  - Immunoglobulin genetics of Ornithorhynchus anatinus (platypus) and Tachyglossus
      aculeatus (short-beaked echidna).
AB  - In this paper, we review data on the monotreme immune system focusing on the
      characterisation of lymphoid tissue and of antibody responses, as well the recent
      cloning of immunoglobulin genes. It is now known that monotremes utilise
      immunoglobulin isotypes that are structurally identical to those found in
      marsupials and eutherians, but which differ to those found in birds and reptiles.
      Monotremes utilise IgM, IgG, IgA and IgE. They do not use IgY. Their IgG and IgA
      constant regions contain three domains plus a hinge region. Preliminary analysis
      of monotreme heavy chain variable region diversity suggests that the platypus
      primarily uses a single VH clan, while the short-beaked echidna utilises at least
      4 distinct VH families which segregate into all three mammalian VH clans.
      Phylogenetic analysis of the immunoglobulin heavy chain constant region gene
      sequences provides strong support for the Theria hypothesis. The constant region
      of IgM has proven to be a useful marker for estimating the time of divergence of
      mammalian lineages.

PMID- 14667847
TI  - Electrolocation in the platypus--some speculations.
AB  - In the platypus, electroreceptors are located in rostro-caudal rows in skin of
      the bill, while mechanoreceptors are uniformly distributed across the bill. The
      electrosensory area of the cerebral cortex is contained within the tactile
      somatosensory area, and some cortical cells receive input from both
      electroreceptors and mechanoreceptors, suggesting a close association between the
      tactile and electric senses. Platypus can determine the direction of an electric
      source, perhaps by comparing differences in signal strength across the sheet of
      electroreceptors as the animal characteristically moves its head from side to
      side while hunting. The cortical convergence of electrosensory and tactile inputs
      suggests a mechanism for determining the distance of prey items which, when they
      move, emit both electrical signals and mechanical pressure pulses. Distance could
      be computed from the difference in time of arrival of the two signals. Much of
      the platypus' feeding is done by digging in the bottom of streams with the bill.
      Perhaps the electroreceptors could also be used to distinguish animate and
      inanimate objects in this situation where the mechanoreceptors would be
      continuously stimulated. Much of this is speculation, and there is still much to
      be learned about electroreception in the platypus and its fellow monotreme, the
      echidna.

PMID- 14667848
TI  - The anatomy of the cerebral cortex of the echidna (Tachyglossus aculeatus).
AB  - The cerebral cortex of the echidna is notable for its extensive folding and the
      positioning of major functional areas towards its caudal extremity. The
      gyrification of the echidna cortex is comparable in magnitude to prosimians and
      cortical thickness and neuronal density are similar to that seen in rodents and
      carnivores. On the other hand, many pyramidal neurons in the cerebral cortex of
      the echidna are atypical with inverted somata and short or branching apical
      dendrites. All other broad classes of neurons noted in therian cortex are also
      present in the echidna, suggesting that the major classes of cortical neurons
      evolved prior to the divergence of proto- and eutherian lineages. Dendritic spine
      density on dendrites of echidna pyramidal neurons in somatosensory cortex and
      apical dendrites of motor cortex pyramidal neurons is lower than that found in
      eutheria. On the other hand, synaptic morphology, density and distribution in
      somatosensory cortex are similar to that in eutheria. In summary, although the
      echidna cerebral cortex displays some structural features, which may limit its
      functional capacities (e.g. lower spine density on pyramidal neurons), in most
      structural parameters (e.g. gyrification, cortical area and thickness, neuronal
      density and types, synaptic morphology and density), it is comparable to
      eutheria.

PMID- 14667849
TI  - Body mass, age and sexual maturity in short-beaked echidnas, Tachyglossus
      aculeatus.
AB  - During the course of this 12 year field study body masses of 11 hatchling
      echidnas (Tachyglossus aculeatus multiaculeatus) and 25 pouch young between the
      ages of 5 and 60 days were recorded. Body mass increased from 0.3 to
      approximately 50 g in the first half of pouch life. It then quadrupled before
      young were placed in a burrow at 45 to 55 days of age. There was a positive
      correlation between the body mass of the female and that of her young at weaning.
      From 33 subadult echidnas located, tagged and radio tracked during this study,
      body masses of 10 were monitored to sexual maturity, i.e. when first encountered
      in a courtship train. Minimum age of sexual maturity ranged between 5 and 12
      years. As subadults, there was no difference between mean body masses of males
      and females. At sexual maturity, mean body mass of females was significantly
      higher. No correlation was found between age at sexual maturity and body mass nor
      was there a significant difference in age of males and females at sexual
      maturity.

PMID- 14667850
TI  - The monotreme genome: a patchwork of reptile, mammal and unique features?
AB  - The first specimen of platypus (Ornithorhynchus anatinus) that reached Britain in
      the late 18th century was regarded a scientific hoax. Over decades the anatomical
      characteristics of these unique mammals, such as egg laying and the existence of
      mammary glands, were hotly debated before they were accepted. Within the last 40
      years, more and more details of monotreme physiology, histology, reproduction and
      genetics have been revealed. Some show similarities with birds or reptiles, some
      with therian mammals, but many are very specific to monotremes. The genome is no
      exception to monotreme uniqueness. An early opinion was that the karyotype,
      composed of a few large chromosomes and many small ones, resembled bird and
      reptile macro- and micro-chromosomes. However, the platypus genome also features
      characteristics that are not present in other mammals, such as a complex
      translocation system. The sex chromosome system is still not resolved. Nothing is
      known about dosage compensation and, unlike in therian mammals, there seems to be
      no genomic imprinting. In this article we will recount the mysteries of the
      monotreme genome and describe how we are using recently developed technology to
      identify chromosomes in mitosis, meiosis and sperm, to map genes to chromosomes,
      to unravel the sex chromosome system and the translocation chain and investigate
      X inactivation and genomic imprinting in monotremes.

PMID- 14667851
TI  - Tactile neural mechanisms in monotremes.
AB  - Monotremes, perhaps more than any other order of mammals, display an enormous
      behavioural reliance upon the tactile senses. In the platypus, Ornithorhynchus
      anatinus, this is manifest most strikingly in the special importance of the bill
      as a peripheral sensory organ, an importance confirmed by electrophysiological
      mapping that reveals a vast area of the cerebral cortex allocated to the
      processing of tactile inputs from the bill. Although behavioural evidence in the
      echidna, Tachyglossus aculeatus, suggests a similar prominence for tactile inputs
      from the snout, there is also a great reliance upon the distal limbs for digging
      and burrowing activity, pointing to the importance of tactile information from
      these regions for the echidna. In recent studies, we have investigated the
      peripheral tactile neural mechanisms in the forepaw of the echidna to establish
      the extent of correspondence or divergence that has emerged over the widely
      different evolutionary paths taken by monotreme and placental mammals.
      Electrophysiological recordings were made from single tactile sensory nerve
      fibres isolated in fine strands of the median or ulnar nerves of the forearm.
      Controlled tactile stimuli applied to the forepaw glabrous skin permitted an
      initial classification of tactile sensory fibres into two broad divisions,
      according to their responses to static skin displacement. One displayed slowly
      adapting (SA) response properties, while the other showed a selective sensitivity
      to the dynamic components of the skin displacement. These purely dynamically
      sensitive tactile fibres could be subdivided according to vibrotactile
      sensitivity and receptive field characteristics into a rapidly adapting (RA)
      class, sensitive to low frequency (</=50 Hz) vibration and another class,
      sensitive to a broader range of vibrotactile frequencies (approx. 50-300 Hz). The
      differential tactile sensitivity of the three principal fibre classes and their
      individual coding characteristics, determined by quantitative stimulus-response
      analysis, indicate first, that this triad of fibre classes can subserve high
      acuity tactile signalling from the echidna footpad and second, that peripheral
      tactile sensory mechanisms are highly conserved across evolutionarily-divergent
      mammalian orders.

PMID- 14667852
TI  - Plasma glucocorticoid concentrations in free-ranging platypuses (Ornithorhynchus
      anatinus): response to capture and patterns in relation to reproduction.
AB  - Energy demands in the platypus are likely to increase in the breeding season,
      which occurs from winter to early spring. Glucocorticoids, which play a major
      role in energy mobilisation, were measured in consecutive blood samples from free
      ranging adults at approximately monthly intervals throughout the year. Glucose
      and free fatty acids were also measured in some samples. Plasma concentrations of
      glucocorticoids rose significantly during the first 30 min after capture,
      accompanied by a rise in free fatty acids, but no corresponding increase in
      glucose concentrations. We observed a strong pattern in plasma glucocorticoids in
      samples collected within 15 min of capture (indicative of pre-disturbance
      concentrations) in different phases of the annual reproductive cycle, with
      significantly higher levels in both males and females in the breeding season
      compared to the non-breeding season. These data, and the decline in tail fat
      stores that occur towards the end of the mating period (around October), suggest
      that platypus experience high-energy demands during this phase of reproduction.
      Plasma glucocorticoid concentrations in females sampled during the lactation
      period (October-February) were relatively low, and similar to those in females
      sampled in the non-breeding, non-lactation period (March-June). The latter
      requires further investigation as results may have been influenced by sampling
      limitations.

PMID- 14667853
TI  - Field energetics of free-living, lactating and non-lactating echidnas
      (Tachyglossus aculeatus).
AB  - We measured daily energy expenditure (DEE) and water turnover rates in lactating
      and non-lactating short beaked echidnas (Tachyglossus aculeatus) using the doubly
      labelled water technique during the lactation period in spring. Reproductively
      inactive echidnas were on average significantly heavier (median: 3354 g; range:
      2929-3780 g; N=4) than lactating females (median: 2695 g; range: 2690-2715 g;
      N=3) during the equivalent time period. The median water flux rate of lactating
      echidnas (152 ml day(-1); range: 120-198 ml day(-1)) did not differ significantly
      from that of non-lactating females (170 ml day(-1); range: 128-227 ml day(-1)).
      The median DEE of echidnas that were lactating was 645 kJ day(-1) (range: 581-850
      kJ day(-1)), which was not different from the median DEE of non-reproductive
      control females (763 kJ day(-1); range: 720-766 kJ day(-1)). Lactating females
      somehow compensate for the energy costs of milk production, resulting in a daily
      energy budget that is not different from that of non-reproductive females. At
      least part of their energy minimising strategy could involve the use of moderate
      heterothermy, allowing a greater proportion of daily energy expenditure to
      diverted to milk production.

PMID- 14667854
TI  - Body temperature in captive long-beaked echidnas (Zaglossus bartoni).
AB  - The routine occurrence of both short-term (daily) and long-term torpor
      (hibernation) in short-beaked echidnas, but not platypus, raises questions about
      the third monotreme genus, New Guinea's Zaglossus. We measured body temperatures
      (T(b)) with implanted data loggers over three and a half years in two captive
      Zaglossus bartoni at Taronga Zoo, Sydney. The modal T(b) of both long-beaks was
      31 degrees C, similar to non-hibernating short-beaked echidnas, Tachyglossus
      aculeatus, in the wild (30-32 degrees C) and to platypus (32 degrees C),
      suggesting that this is characteristic of normothermic monotremes. T(b) cycled
      daily, usually over 2-4 degrees C. There were some departures from this pattern
      to suggest periods of inactivity but nothing to indicate the occurrence of long
      term torpor. In contrast, two short-beaked echidnas monitored concurrently in the
      same pen showed extended periods of low T(b) in the cooler months (hibernation)
      and short periods of torpor at any time of the year, as they do in the wild.
      Whether torpor or hibernation occurs in Zaglossus in the wild or in juveniles
      remains unknown. However, given that the environment in this study was conducive
      to hibernation in short-beaks, which do not easily enter torpor in captivity, and
      their large size, we think that torpor in wild adult Zaglossus is unlikely.

PMID- 14667855
TI  - Control of breathing in the echidna (Tachyglossus aculeatus) during hibernation.
AB  - Resting non-hibernating echidnas are characterised by low metabolic rates, but
      also have a very low respiratory frequency and a variable respiratory minute
      volume, often resulting in low levels of arterial O(2) and high CO(2). As the
      echidna lies at one physiological extreme among the hibernators, in terms of its
      large size and low metabolism and ventilatory requirement when not hibernating, a
      study of control of breathing during hibernation in echidnas should provide a
      useful test of the generality of various models. We used non-invasive techniques
      to study breathing patterns and the control of ventilation in 6 echidnas.
      Hibernating echidnas (T(b) range 7-10 degrees C) showed episodic breathing with
      bursts of breaths (average 36+/-16 breaths in 24+/-5 min) followed by a period of
      apnea (76+/-17 min) then a series (8+/-4) of slow breaths at 14+/-1 min intervals
      leading up to the next burst. Increasing CO(2) levels in the inspired air
      increased the number of breaths in a burst, eventually leading to continuous
      breathing. Inter burst breaths were controlled by O(2): hypoxia increased inter
      burst breaths, and decreased burst length, while hyperoxia abolished inter burst
      breaths and increased the apneic period. Overall, while CO(2) was a strong
      respiratory stimulus in hibernating echidnas, O(2) had little effect on total
      ventilation, but did have a strong effect on the breathing pattern.

PMID- 14667856
TI  - Review of the monotreme fossil record and comparison of palaeontological and
      molecular data.
AB  - Monotremes have traditionally been considered a remnant group of mammals
      descended from archaic Mesozoic stock, surviving to the present day on the
      relatively isolated Australian continent. Challenges to this orthodoxy have been
      spurred by discoveries of 'advanced' Cretaceous monotremes (Steropodon galmani,
      Archer, M., et al., 1985. First Mesozoic mammal from Australia-an Early
      Cretaceous monotreme, Nature. 318, 363-366) as well as by results from molecular
      data linking monotremes to therian mammals (specifically to marsupials in some
      studies). This paper reviews the monotreme fossil record and briefly discusses
      significant new information from additional Cretaceous Australian material.
      Mesozoic monotremes (including S. galmani) were a diverse group as evidenced by
      new material from the Early Cretaceous of New South Wales and Victoria currently
      under study. Although most of these new finds are edentulous jaws (limiting
      dental comparisons and determination of dietary niches), a range of sizes and
      forms has been determined. Some of these Cretaceous jaws exhibit archaic features
      in particular evidence for the presence of a splenial bone in S. galmani-not seen
      in therian mammals or in post-Mesozoic (Tertiary and Quaternary) monotreme taxa.
      Tertiary monotremes were either archaic ornithorhynchids (toothed platypuses in
      the genera Monotrematum and Obdurodon) or tachyglossids (large echidnas in the
      genera Megalibgwilia and Zaglossus). Quaternary ornithorhynchid material is
      referable to the sole living platypus species Ornithorhynchus anatinus.
      Quaternary echidnas, however, were moderately diverse and several forms are known
      (Megalibgwilia species; 'Zaglossus' hacketti; Zaglossus species and Tachyglossus
      aculeatus).

PMID- 14667857
TI  - Ventilation and metabolic rate in the platypus: insights into the evolution of
      the mammalian breathing pattern.
AB  - The platypus (Ornithorhyncus anatinus) is characterized by a rate of oxygen
      consumption (V(O2))that is higher than that reported for other similar sized
      monotremes, similar to marsupials and somewhat lower than eutherians. The
      platypus is also characterized by a breathing pattern, more typical of a diving
      mammal, with a high 'inspiratory drive' and a post-inspiratory pause. Further,
      the platypus reveals an attenuated hyperventilatory response to hypoxia and a
      reduced hyperpnoea to hypercapnia; such a response to these chemical stimuli is
      commonly observed in semi-fossorial and diving mammals. Nevertheless, under
      conditions of normoxia, ventilation (V(E))is matched to (V(O(2)) such that the
      convection requirement (V(E)/V(O2)) is similar to that reported for other mammals
      (approx. 37). The apparent consistency of the convection requirement in mammals
      suggests the blueprint for the design of the mammalian respiratory system has
      remained an interspecies constant in the three divergent extant sub-classes of
      mammals.

PMID- 14667858
TI  - Antibody response to sheep red blood cells in platypus and echidna.
AB  - There is limited information regarding the kinetics of antibody responses
      exhibited by the platypus and the echidna in response to a T cell dependent
      antigen. In this preliminary study a platypus, an echidna and a rabbit were
      inoculated with sheep red blood cells to compare their antibody responses and
      kinetics. The antibody titres, produced by the platypus and echidna, were less
      than those elicited in the rabbit. Furthermore, the echidna and platypus
      exhibited a weak secondary response. This was most likely due to a failure of the
      platypus and echidna to undergo the characteristic IgM to IgG isotype switch
      following second antigen exposure. The conformational structure of these
      antibodies may differ from eutherian antibodies. This was further supported by a
      heat sensitivity experiment that indicated that these antibodies are more labile
      than rabbit immunoglobulins and therefore structurally less stable.

PMID- 14667859
TI  - Conservative treatment may be beneficial for young women with atypical
      endometrial hyperplasia or endometrial adenocarcinoma.
AB  - OBJECTIVE: To evaluate whether an alternative treatment to radical hysterectomy
      exists for young women with endometrial adenocarcinoma. DESIGN: A review of the
      literature (70 articles) plus personal results. SETTING: University hospital.
      PATIENT(S): Women with atypical endometrial hyperplasia or adenocarcinoma. MAIN
      OUTCOME MEASURE(S): The recurrence rate and the pregnancy rate after conservative
      therapy. CONCLUSION(S): Conservative treatment of well-differentiated stage I
      endometrial adenocarcinoma can be considered in young patients, with close
      surveillance to diagnose any possible recurrence.

PMID- 14667860
TI  - Effects of letrozole on superovulation with gonadotropins in women undergoing
      intrauterine insemination.
AB  - OBJECTIVE: To investigate the effects of letrozole in patients undergoing
      superovulation with gonadotropins and IUI. DESIGN: Retrospective analysis.
      SETTING: Academic teaching hospital. PATIENT(S): Women younger than 40 years of
      age with patent fallopian tubes and infertility of more than 1 year in duration
      who were undergoing IUI and gonadotropin therapy. INTERVENTION(S): Gonadotropins
      alone administered from day 3 or a combination of letrozole, 5 mg/d on day 3 to
      7, and gonadotropins starting on day 5 of the menstrual cycle. Ultrasonography
      was performed before initiation of treatment, on day 9 of menstrual cycle, and as
      required thereafter until the dominant follicle reached 18 mm in diameter.
      Ovulation was triggered with 10,000 IU of hCG, and IUI was performed 24 and 48
      hours later. MAIN OUTCOME MEASURE(S): Gonadotropin requirements, endometrial
      thickness, number of follicles, and pregnancy rate. RESULT(S): All 205 IUI
      treatment cycles conducted from March 2001 to March 2002 were included.
      Gonadotropins alone were used in 145 cycles and combination therapy was used in
      60 cycles. Patients cotreated with letrozole required fewer gonadotropin
      administrations (median difference, 300 IU [95% confidence interval (CI), 225-375
      IU]), developed more follicles larger than 14 mm (median difference, 1 follicle
      [95% CI, 1-2 follicles), and had a thinner endometrium (median difference, 1 mm
      [95% CI, 0.4-1.6 mm]). The pregnancy rate did not differ between patients using
      gonadotropin alone and those using gonadotropin plus letrozole (20.9% vs. 21.6%).
      CONCLUSION(S): The addition of letrozole to gonadotropins decreases gonadotropin
      requirements, increases the number of pre-ovulatory follicles and decreases
      endometrial thickness, without a negative effect on pregnancy rates.

PMID- 14667861
TI  - Comparison of the effects of letrozole and clomiphene citrate on ovarian
      follicles, endometrium, and hormone levels in the rat.
AB  - OBJECTIVE: To compare the effects of letrozole and clomiphene citrate in the rat
      in terms of number of ovarian follicles; endometrial thickness; and serum levels
      of E2, FSH, LH, and T. DESIGN: Controlled prospective study. SETTING: University
      research laboratory. ANIMAL(S): Thirty sexually mature female Wistar-Albino rats
      that were 20 weeks of age. INTERVENTION(S): Letrozole, 5 mg/kg of body weight
      daily (10 rats); clomiphene citrate, 100 microg/kg daily (10 rats); or saline
      solution, 2 mL/d (10 rats). After 2 days, rats were euthanized and
      ovariectomized. MAIN OUTCOME MEASURE(S): Number of mature follicles, endometrial
      thickness, and serum levels of hormones. RESULT(S): Mean levels of FSH, LH, E2,
      and T; number of mature follicles; and ovary size differed among the groups,
      whereas the mean endometrial thickness did not differ. CONCLUSION(S): In rats,
      the effect of letrozole on follicular maturation is similar to that of clomiphene
      citrate.

PMID- 14667862
TI  - Ovulation induction is not the same as superovulation: the effect of selective
      estrogen receptor modulators and aromatase inhibitors.

PMID- 14667863
TI  - Letrozole: ovulation or superovulation?

PMID- 14667864
TI  - Ovulation induction in women with infertility: a new indication for aromatase
      inhibitors.

PMID- 14667866
TI  - Risk factors and clinical features of recurrent ectopic pregnancy: a case control
      study.
AB  - OBJECTIVE: To compare signs and symptoms between patients with recurrent and
      single ectopic pregnancies. DESIGN: Case-control study. SETTING: University
      medical center. PATIENT(S): Three hundred six women with single ectopic
      pregnancies and 61 women with recurrent ectopic pregnancies. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Risk factors, historical factors, and findings at
      presentation that may predispose to recurrent ectopic pregnancy. RESULT(S): The
      risk of recurrent ectopic pregnancy was increased with a history of surgery,
      history of live birth, and history of spontaneous miscarriage and not with a
      history of gonorrhea, chlamydia, pelvic inflammatory disease, Caesarean section,
      or pregnancy termination. Patients with a recurrent ectopic pregnancy had a
      nonsignificant trend toward higher initial hCG values. The majority of
      ultrasounds in both groups were nondiagnostic on presentation. The patients with
      recurrent ectopic pregnancy were less likely to have bleeding on initial
      presentation, though both groups had similar complaints of pain. CONCLUSION(S):
      Secondary prevention of ectopic pregnancy is problematic because of the paucity
      of risk factors that can be modified to diminish the odds of recurrence.
      Clinicians' ability to both diagnose and counsel patients at risk for recurrent
      ectopic pregnancy can be optimized by awareness of the clinical features of this
      condition.

PMID- 14667867
TI  - Acute and chronic presentation of ectopic pregnancy may be two clinical entities.
AB  - OBJECTIVE: The diagnosis of ectopic pregnancy (EP) is often confirmed at
      presentation (acute), but often requires serial beta-hCG levels to confirm the
      diagnosis (chronic). The purpose of this study is to analyze whether these
      clinical presentations represent a spectrum of disease. DESIGN: The retrospective
      cohort study of 452 patients diagnosed with EP at the University of Pennsylvania
      in the years 1990-1999. SETTING: University of Pennsylvania, Philadelphia,
      Pennsylvania. PATIENT(S): Four hundred fifty-two patients diagnosed with EP.
      Patients diagnosed with EP were divided into two groups according to the time of
      diagnosis. MAIN OUTCOME MEASURE(S): A total of 37 parameters were examined
      including historic and demographic factors, findings at presentation, and
      treatment and outcome variables. RESULT(S): The two groups were similar in terms
      of historic EP risk factors. Multivariable analysis demonstrates that women with
      a chronic presentation were less likely to have received fertility medications
      (odds ratio [OR] 0.23; 95% confidence interval [CI] 0.06-0.84), less likely to
      present with pain (OR 0.29; 95% CI 0.12-0.71), have a lower beta-hCG level at
      presentation (9,849 mIU/mL +/- 16,726 vs. 1,787 mIU/mL +/- 4,717), lower chance
      of rupture (OR 0.19; 95% CI 0.05-0.73), and less frequently have blood type 0.
      CONCLUSION(S): Women diagnosed with ectopic pregnancy can be categorized into two
      groups, those with an acute presentation and those with a chronic presentation.
      Differences in risk factors, presentation, and outcome may reflect differences in
      trophoblast viability or invasive potential.

PMID- 14667868
TI  - The graduated embryo score predicts the outcome of assisted reproductive
      technologies better than a single day 3 evaluation and achieves results
      associated with blastocyst transfer from day 3 embryo transfer.
AB  - OBJECTIVE: To evaluate the graduated embryo score (GES) for predicting assisted
      reproductive technology (ART) outcome compared to a single morphologic evaluation
      on day 3 of culture (grade A: > or =7 cells; <20% fragmentation). DESIGN:
      Prospective cohort analysis. SETTING: Private practice. PATIENT(S): Women aged
      <40 years with a normal uterine cavity treated with ART (n = 106).
      INTERVENTION(S): Embryos were graded by GES and by day 3 morphologic
      characteristics alone before ET. Cycle outcomes were compared with embryo grade.
      MAIN OUTCOME MEASURE(S): Ongoing gestation and implantation rates. RESULT(S):
      Overall ongoing gestation and implantation rates were 48% and 26%, respectively.
      With 1+ embryo GES > or =70 (n = 77), the rates were 62% and 36%, respectively,
      which were significantly higher than for those with 0 embryos GES > or =70 (n =
      29). With 1+ grade A embryo (n = 102), the rates were 50% and 27%, respectively.
      Transfer of more than one embryo GES > or =70 did not improve the pregnancy rate,
      but did increase the risk of multiple gestations. A single day 3 evaluation had
      an extremely low specificity (7%) compared to GES (47%). Graduated embryo scoring
      (GES) was an excellent predictor of pregnancy and implantation rates from
      blastocyst transfer. Day of transfer did not affect pregnancy rates, although
      implantation was higher from day 5 embryo transfer (ET) than from day 3 ET, as
      fewer embryos were transferred. CONCLUSION(S): Transfer of one or more embryo GES
      > or =70 predicts pregnancy and implantation rates better than a single
      morphologic evaluation on day 3 and achieves ART outcomes associated with
      blastocyst transfer from day 3 ET, making extended culture unnecessary for most
      patients.

PMID- 14667869
TI  - Delay of embryo transfer to day 5 results in decreased initial serum beta-human
      chorionic gonadotropin levels.
AB  - OBJECTIVE: To investigate the impact of delaying the transfer of in vitro
      fertilized embryos to day 5 on embryo development by comparing serum beta-hCG
      levels in pregnancies established after day 3 embryo transfers and those after
      day 5 blastocyst transfers at equivalent time intervals after fertilization.
      DESIGN: A retrospective analysis. SETTING: Assisted reproductive technology
      center in an academic research environment. PATIENT(S): Women who had an embryo
      transfer procedure performed after in vitro fertilization (IVF) at Northwestern
      University's IVF Program between January 1999 and December 2001 were included in
      this study. INTERVENTION(S): Embryo transfer was performed either on day 3 or day
      5 after oocyte retrieval for IVF (day 0), depending on the availability of good
      quality embryos on day 3. MAIN OUTCOME MEASURE(S): Serum beta-hCG concentrations
      determined 13 and 15 days after fertilization in pregnancies established by
      transferring cleavage-stage embryos on day 3 or blastocysts on day 5. RESULT(S):
      In singleton pregnancies, serum beta-hCG concentrations were 75 +/- 54 (mean +/-
      SD, n = 203) or 62 +/- 41 (n = 109) IU/mL after day 3 or day 5 transfers,
      respectively. In twin pregnancies, the beta-hCG concentrations were 162 +/- 105
      (n = 52) or 109 +/- 55 (n = 49) after day 3 or day 5 transfers, respectively. The
      percentage increases in beta-hCG concentrations between the first and second
      measurements were similar in the two groups (day 3: 144 +/- 109, day 5: 142 +/-
      63, not statistically significant). CONCLUSION(S): Initial beta-hCG
      concentrations in pregnancies resulting from day 5 transfers were lower than
      those from day 3 transfers when assessed at equivalent intervals from
      fertilization. This suggests that embryo development or implantation may be
      impaired by the additional 2 days in culture.

PMID- 14667871
TI  - Uterine cavity findings and hysteroscopic interventions in patients undergoing in
      vitro fertilization-embryo transfer who repeatedly cannot conceive.
AB  - OBJECTIVE: To assess hysteroscopic findings in patients undergoing IVF-ET who
      repeatedly failed to conceive despite transfer of good-quality embryos. DESIGN:
      Prospective, observational study. SETTING: Clinical research unit for
      reproductive medicine in a private clinic. PATIENT(S): Fifty-five patients with a
      normal uterine cavity on hysterosalpingography before the initial IVF-ET cycle
      and two previous failed IVF-ET attempts despite transfer of a minimum of two good
      quality embryos on each occasion. INTERVENTION(S): Standard transvaginal
      ultrasonography and diagnostic and therapeutic hysteroscopy. MAIN OUTCOME
      MEASURE(S): Endometrial findings on transvaginal ultrasonography and hysteroscopy
      and outcome of the cycles after surgical hysteroscopy and antibiotic therapy.
      RESULT(S): Twenty-five (45%) patients had abnormal endometrial findings and
      underwent treatment to correct the lesions. All patients underwent a third IVF-ET
      cycle. Pregnancy (50% vs. 20%) and implantation (19% vs. 5.5%) rates were
      significantly higher in patients who were treated for uterine abnormalities than
      in patients who had normal uterine cavities on hysteroscopy. CONCLUSION(S): The
      incidence of pathologic findings on hysteroscopy is high in patients with
      repeated failures of IVF-ET. Evaluation of endometrial integrity by hysteroscopy
      is highly valuable and should be applied to all such cases.

PMID- 14667870
TI  - Transfer of nonselected transferable day 3 embryos in low embryo producers.
AB  - OBJECTIVE: To examine the implantation potential of embryos from assisted
      reproductive technology cycles with low embryo production and to assess the
      effects of clinical variables and embryo scores (ES) on pregnancy outcome.
      DESIGN: Prospective clinical study. SETTING: Assisted reproductive technology
      unit in a tertiary medical center. PATIENT(S): From July 1998 to December 2001,
      280 cycles in 229 infertile couples produced a limited number of one, two, or
      three embryos 3 days after oocyte retrieval and underwent fresh embryo transfer
      (ET). INTERVENTION(S): Embryos with two or more blastomeres were scored and
      transferred. MAIN OUTCOME MEASURE(S): ES and implantation rate per ET. RESULT(S):
      Of 863 fresh ET cycles during the study period, 32.4% (280) were low embryo
      producers. Among them, there were no significant differences in average ES of
      individual embryos in single, dual, or triple ET or in embryos obtained from
      patients with low or high E2 responses, or young or old age. Embryos derived from
      conventional IVF had a better ES than those derived from intracytoplasmic sperm
      injection. The clinical pregnancy rate was strongly correlated with the
      cumulative ES. Implantation rates were similar among and between groups, with an
      average rate of 15.9%. CONCLUSION(S): Embryos of low embryo producers had an
      inherently low implantation potential that appeared to be unrelated to the number
      of embryos transferred, female age, ovarian E2 genesis, or fertilization method.
      The cumulative ES can serve as a predictor of pregnancy.

PMID- 14667872
TI  - Predictive value of the number of oocytes retrieved at ultrasound-directed
      follicular aspiration with regard to fertilization rates and pregnancy outcome in
      intracytoplasmic sperm injection treatment cycles.
AB  - OBJECTIVE: To determine the number of oocytes sufficient for satisfactory
      fertilization and pregnancy rates in intracytoplasmic sperm injection cycles.
      DESIGN: A retrospective analysis. SETTING: A private assisted conception unit.
      PATIENT(S): Women in whom at least one oocyte was retrieved in consecutive
      ultrasound-directed follicular aspirations between June 1999 and June 2001.
      INTERVENTION(S): Standard protocol for pituitary down-regulation and ovarian
      stimulation. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, embryos
      transferred, fertilization, and pregnancy rates. RESULT(S): The numbers of
      oocytes obtained per cycle were classified into groups A, B, C, and D, consisting
      of 110, 124, 96, and 122 cycles, with 1-5, 6-10, 11-15, >15 oocytes retrieved
      from each patient in each group, respectively. The chance of not obtaining a
      viable oocyte for injection was highest in group A (5.5%). Most fertilization
      failures occurred in group A (11.8%). Total cleavage failure occurred in the
      greatest percentage of cycles in group A (3.6%) with a significantly lower mean
      number of embryos (1.9 +/- 1.7) being transferred. The clinical pregnancy rate
      was also lowest in group A (7.1%) compared with groups B (25.8%), C (20.8%), and
      D (23.8%). CONCLUSION(S): Retrieval of between 6 and 10 oocytes per patient and
      transfer of a maximum of three cleavage-stage embryos results in high pregnancy
      rates.

PMID- 14667873
TI  - Blastocyst formation, karyotype, and mitochondrial DNA of interspecies embryos
      derived from nuclear transfer of human cord fibroblasts into enucleated bovine
      oocytes.
AB  - OBJECTIVE: To establish an interspecies somatic cell nuclear transfer (iSCNT)
      technique for deriving blastocysts having human chromosome complements without
      sacrificing human oocytes. DESIGN: Prospective, randomized study undertaken in
      vitro. SETTING: University-affiliated hospital and laboratory, Seoul National
      University. PATIENT(S): Postpartum women with natural spontaneous vaginal
      delivery. INTERVENTION(S): Human cord fibroblasts were retrieved from five
      postpartum women from whom informed consent was obtained. After subculture and
      cryopreservation, serum-starved cells were transferred into enucleated bovine
      oocytes. MAIN OUTCOME MEASURE(S): Embryo development, karyotype, and the presence
      of mitochondrial DNA (mtDNA). RESULT(S): A total 1,742 oocytes were provided for
      iSCNT and results showed that both fibroblast batch and reconstruction method
      significantly affected iSCNT outcome. An iSCNT using a single DC pulse of 1.9-2.1
      kV/cm for 20 microseconds yielded better rates of fusion (30%-56%) and cleavage
      (36%) than the other iSCNT protocols. Four to 9% interspecies embryos produced
      with the optimized method developed to morulae or blastocysts after cultured in a
      serum-free medium. Results from karyotyping demonstrated that 56% of interspecies
      embryos evaluated had human chromosome complements. In polymerase chain reaction
      (PCR) analysis of a single embryo, both human and bovine mtDNAs were detected
      until the 16-cell stage, whereas only the bovine mtDNA was found beyond the
      morula stage. CONCLUSION(S): An iSCNT using human cord fibroblasts and bovine
      oocytes can yield blastocysts and the results of karyotyping and mtDNA analysis
      confirmed the feasibility of the iSCNT technique.

PMID- 14667874
TI  - A prospective longitudinal study of the physical, psychomotor, and intellectual
      development of singleton children up to 5 years who were conceived by
      intracytoplasmic sperm injection compared with children conceived spontaneously
      and by in vitro fertilization.
AB  - OBJECTIVE: To assess the somatic, psychomotor, and intellectual development of
      children conceived through intracytoplasmic single sperm injection (ICSI) over
      the whole preschool period. DESIGN: Prospective, controlled, cohort study.
      SETTING: Fertility clinic in Brussels, Belgium. PATIENT(S): Sixty-six ICSI
      conceived children prospectively compared with 52 IVF-conceived and 59
      spontaneously conceived children. All children were full-term singletons.
      INTERVENTION(S): Home visits by a trained psychologist. Standardized interviews.
      Assessments using the revised Brunet-Lezine scale and the revised Wechsler
      preschool and primary scale of intelligence. MAIN OUTCOME MEASURE(S): Physical
      growth and general health. Formal developmental and intellectual assessments.
      RESULT(S): Children conceived by ICSI were healthy: no significant differences
      appeared in the incidence of combined congenital malformations (11.3%), health
      problems (44.1%), surgical interventions (18.6%), and hospitalizations (6.8%),
      nor for the developmental assessments (mean developmental quotient at 9 months:
      93.9; at 18 months: 102.0). For the intellectual assessments, the between-group
      differences disappeared when adjusted for levels of parental education (mean
      intelligence quotient at 3 years: 97.0; at 5 years: 103.3). CONCLUSION(S): This
      pilot study shows that throughout the preschool period, ICSI-conceived children
      have psychomotor and intellectual development similar to that of IVF-conceived
      and spontaneously conceived children. These conclusions need to be confirmed by
      multicenter studies.

PMID- 14667875
TI  - Recombinant human follicle-stimulating hormone as a pretreatment for idiopathic
      oligoasthenoteratozoospermic patients undergoing intracytoplasmic sperm
      injection.
AB  - OBJECTIVE: To evaluate the efficacy of recombinant human FSH pretreatment in
      improving fertilization and pregnancy rates in oligozoospermic patients who are
      undergoing ICSI. DESIGN: Prospective, controlled, clinical study. SETTING: A
      research institute's reproductive unit. PATIENT(S): Thirty-three subjects with
      idiopathic oligoasthenoteratozoospermia who failed to conceive after previous
      ICSI attempts. INTERVENTION(S): Treatment with recombinant human FSH 150 IU for 3
      months (23 patients) or no treatment (10 patients); clinical, hormonal, and
      seminal evaluation before and after treatment. MAIN OUTCOME MEASURE(S):
      Testicular volume, sperm parameters, FSH, LH, T, E(2), and inhibin B plasma
      levels, E/T ratio, and fertilization and pregnancy rates. RESULT(S): Treatment
      with 150 IU of FSH induced a significant increase in testicular volume and sperm
      parameters. The mean fertilization rate (FR) after ICSI cycles was higher,
      although not significantly, in treated patients when compared with controls (62.3
      +/- 22.4 vs. 47.2 +/- 20.4). A strong negative correlation was observed between
      FR and serum FSH, inhibin B and E/T ratio in controls, whereas in treated
      patients, FR correlated with posttreatment inhibin B levels. The pregnancy rate
      in the entire treated group was 30.4%. No pregnancies were recorded in the
      control group. CONCLUSION(S): Recombinant human FSH may be a valuable
      pretreatment for oligozoospermic patients undergoing ICSI and may influence
      testicular paracrine activity.

PMID- 14667876
TI  - Correlation between sperm motility and sperm chromatin structure assay
      parameters.
AB  - OBJECTIVE: To evaluate the association between chromatin structure and sperm
      motility. DESIGN: Cross-sectional prospective study. SETTING: Scanian Andrology
      Centre, Malmo, Sweden; ENEA Casaccia, Rome, Italy; and Department of Occupational
      Medicine, Aarhus University, Aarhus, Denmark. PATIENT(S): One hundred seventy-one
      males from Danish first pregnancy planner couples (group 1) and 278 Swedish
      military conscripts (group 2). MAIN OUTCOME MEASURE(S): Sperm chromatin structure
      assay (SCSA) parameters, DNA fragmentation index (DFI), high DNA stainable (HDS),
      and sperm motility, which was evaluated manually and by use of computer-aided
      sperm analysis (CASA). RESULT(S): A statistically significant negative
      correlation between DFI and the CASA percentage of motile sperms (group 1: r = 
      0.53; group 2: r = -0.38) was found. For the manual motility assessment, the
      correlation coefficients were slightly lower. Furthermore, HDS correlated
      negatively with CASA sperm motility (group 1: r = -0.39; group 2: r = -0.36) and
      percentage of World Health Organization category A motile sperm. In multiple
      linear regression analysis, concentration and SCSA parameters, but not the time
      of abstinence, were statistically significant predictors of sperm motility.
      CONCLUSION(S): There is a moderate correlation between sperm motility and SCSA
      parameters. The study supports the assumption that both SCSA and motility can be
      relatively independent predictors of male fertility.

PMID- 14667877
TI  - Pregnancy rates are higher with intracytoplasmic morphologically selected sperm
      injection than with conventional intracytoplasmic injection.
AB  - OBJECTIVE: To verify whether microinjection into retrieved oocytes of motile
      spermatozoa with morphologically normal nuclei, strictly defined by high power
      light microscopy (x >6000), improves the IVF/intracytoplasmic sperm injection
      (ICSI) pregnancy rate in couples with repeated ICSI failures. DESIGN: Comparative
      prospective study testing routine IVF/ICSI outcome parameters against those of
      modified ICSI based on morphological selection of spermatozoa with normal nuclei.
      SETTING: Male factor fertility laboratory and IVF center. PATIENT(S): Sixty-two
      couples, with at least two previous consequent pregnancy failed ICSI cycles,
      underwent a single ICSI trial preceded by morphological selection of spermatozoa
      with normal nuclei. Fifty of these couples were matched with couples who
      underwent a routine ICSI procedure at the same IVF center and exhibited the same
      number of previous ICSI failures. INTERVENTION(S): Standard ICSI and modified
      ICSI. MAIN OUTCOME MEASURE(S): ICSI pregnancy rate. RESULT(S): The matching study
      revealed that pregnancy rate after modified ICSI was significantly higher than
      that of the routine ICSI procedure (66.0% vs. 30.0%). CONCLUSION(S):
      Microinjection into retrieved oocytes of selected spermatozoa with strictly
      defined morphologically normal nuclei improves significantly the incidence of
      pregnancy in couples with previous ICSI failures.

PMID- 14667878
TI  - Effects of age on DNA double-strand breaks and apoptosis in human sperm.
AB  - OBJECTIVE: This study was designed to explore the relationship between men's age
      and DNA damage and apoptosis in human spermatozoa. DESIGN: Semen samples were
      collected from men between the ages of 20 and 57 years. Sperm DNA double-strand
      breaks were assessed using the neutral microgel electrophoresis (comet) assay,
      and apoptosis was estimated using the DNA diffusion assay. SETTING: Academic
      medical center. PATIENT(S): Sixty-six men aged 20 to 57 years were recruited from
      infertility laboratory and general populations and consented to donate a semen
      sample. Recruitment was determined by time and day of analysis; the only
      exclusions were for azoospermia, prostatitis, or prior cancer therapy.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): DNA damage and apoptosis in human
      sperm. RESULT(S): Age correlated with an increasing percentage of sperm with
      highly damaged DNA (range: 0-83%) and tended to inversely correlate with
      percentage of apoptotic sperm (range: 0.3%-23%). For example, percentage of sperm
      with highly damaged DNA, comet extent, DNA break number, and other comet measures
      was statistically significantly higher in men aged 36-57 years than in those aged
      20-35 years, but percentage apoptosis was statistically significantly lower in
      the older group. Semen analysis showed percentage motility to be significantly
      higher in younger age groups. CONCLUSION(S): This study clearly demonstrates an
      increase in sperm double-stranded DNA breaks with age. Our findings also suggest
      for the first time an age-related decrease in human sperm apoptosis. These novel
      findings may indicate deterioration of healthy sperm cell selection process with
      age.

PMID- 14667879
TI  - Evaluation of nuclear DNA damage in spermatozoa from infertile men with
      varicocele.
AB  - OBJECTIVE: To examine levels of sperm DNA damage and oxidative stress (OS) in
      infertile men with varicocele. DESIGN: Prospective controlled study. SETTING:
      Male infertility clinic, Glickman Urological Institute, Cleveland Clinic
      Foundation, Cleveland, Ohio. PATIENT(S): Thirty-one infertility patients and 16
      fertile controls. INTERVENTION(S): Sperm DNA fragmentation index (DFI), levels of
      seminal reactive oxygen species (ROS), and total antioxidant capacity (TAC) were
      assessed using the sperm chromatin structure assay, chemiluminescence assay, and
      enhanced chemiluminescence assay, respectively. ROS-TAC score was calculated as a
      measure of OS. MAIN OUTCOME MEASURE(S): Median (interquartile range) DFI and ROS
      TAC scores. RESULT(S): Sixteen of the 31 patients had left varicocele [grade I (n
      = 3), grade II (n = 10), and grade III(n = 3)], and the remaining 15 had normal
      genital examination. Patients with varicoceles had significantly higher percent
      DFI than controls (25%, range: 20%-35%; vs. 15%, range: 10%-22%). Patients with
      varicoceles had significantly lower ROS-TAC scores (21, range: 9.5-31) than the
      infertile patients with normal genital examination (34, range: 28-42) or the
      controls (40.3, range: 38-44). CONCLUSION(S): Infertile men with varicoceles
      showed significantly increased spermatozoal DNA damage that appears to be related
      to high levels of OS in semen.

PMID- 14667880
TI  - Significance of mRNA levels of connexin37, connexin43, and connexin45 in
      luteinized granulosa cells of controlled hyperstimulated follicles.
AB  - OBJECTIVE: To evaluate the mRNA levels of connexins in different sizes of
      luteinized follicles. DESIGN: Semiquantitative reverse transcriptase-polymerase
      chain reaction (RT-PCR) to determine the connexin mRNA levels in the granulosa
      cells of 91 luteinized follicles. SETTING: Academic tertiary care medical center
      and research unit of university. PATIENT(S): Ninety-one female patients on
      controlled ovarian hyperstimulation (COH). INTERVENTION(S): Sonoguided aspiration
      to collect the oocytes and the granulosa cells simultaneously. MAIN OUTCOME
      MEASURE(S): The RT-PCR data are normalized by comparing the intensity of the
      connexins to the intensity of internal controls (beta-actin). The follicles are
      grouped according to the size and the mRNA levels of the connexins. The
      correlations among the size of the follicles, the outcome of oocytes, and the
      mRNA levels of the connexins are compared by Fisher's exact test and Mann-Whitney
      test. RESULT(S): The mRNA levels of the connexins are low in the follicles equal
      or larger than 5.5 mL. High cx43 levels are linked to good prognosis of oocytes.
      CONCLUSION(S): The luteinized granulosa cells from the large follicles are
      relatively quiescent in the connexin mRNA expression. In addition to the volume,
      the mRNA levels of cx43 may serve as a marker to predict the outcome of oocytes.

PMID- 14667881
TI  - Premature luteinization during gonadotropin-releasing hormone antagonist cycles
      and its relationship with in vitro fertilization outcome.
AB  - OBJECTIVE: To determine the prevalence and the effect of premature luteinization
      in GnRH antagonist IVF-ET cycles. DESIGN: Prospective observational study.
      SETTING: In vitro fertilization-embryo transfer (IVF-ET) program at the Instituto
      Valenciano de Infertilidad. PATIENT(S): Eighty-one infertile patients undergoing
      controlled ovarian hyperstimulation with gonadotropins and GnRH antagonist for
      IVF-ET. INTERVENTION(S): Gonadotropin-releasing hormone (GnRH) antagonist was
      administered from stimulation day 6. Serum P, E(2), and LH were determined on the
      day of hCG administration. MAIN OUTCOME MEASURE(S): Cycles were grouped according
      to serum P level on the day of hCG administration (<1.2 ng/mL or > or =1.2
      ng/mL). Clinical pregnancy and implantation rates were determined. RESULT(S): The
      incidence of premature luteinization was 38.3%. Total recombinant FSH dose and
      stimulation days differed significantly between the groups. Pregnancy rate (25.8%
      vs. 54.0%) and implantation rate (13.8% vs. 32.0%) were significantly lower in
      the premature luteinization group. CONCLUSION(S): Premature luteinization during
      GnRH antagonist IVF-ET cycles is a frequent event that is associated with lower
      pregnancy and implantation rates. Progesterone elevations are not related to
      serum LH levels and may reflect the mature granulosa cell response to high FSH
      exposure.

PMID- 14667883
TI  - Effects of mifepristone on expression of endothelial nitric oxide synthase in
      human endometrium during the implantation phase.
AB  - OBJECTIVE: To investigate the effects of the antiprogestin mifepristone on
      expression of endothelial (eNOS) nitric oxide synthase in human endometrium
      during the implantation phase. DESIGN: Prospective clinical study. SETTING:
      Teaching university hospital. PATIENT(S): Endometrial samples were obtained from
      nine healthy women with proven fertility. INTERVENTION(S): One control and one
      treatment cycle were performed. Treatment with 200 mg of mifepristone was
      administered on LH day 2. Endometrial biopsy specimens were obtained on LH day 6
      to 8. MAIN OUTCOME MEASURE(S): Expression of eNOS was identified by using
      immunohistochemistry and Western blot assay, and messenger RNA levels were
      determined with semiquantitative reverse transcription polymerase chain reaction.
      RESULT(S): Endothelial nitric oxide synthase was detected in vascular endothelium
      and glandular epithelium in the endometrium. Treatment with mifepristone
      significantly decreased eNOS expression in the endometrial glandular epithelium
      but did not affect endothelial eNOS. CONCLUSION(S): Mifepristone has differential
      effects on eNOS expression in the epithelium and endothelium in the human
      endometrium at the time of implantation. The results support a role of epithelial
      eNOS in human endometrial receptivity.

PMID- 14667882
TI  - Laparoscopic evaluation following failure to achieve pregnancy after ovulation
      induction with clomiphene citrate.
AB  - OBJECTIVE: To assess the value of laparoscopic evaluation of the pelvis after
      failure to achieve pregnancy with clomiphene citrate-induced ovulation and to
      determine whether predictors for significant pelvic pathology can be isolated.
      DESIGN: Retrospective study. SETTING: Tertiary care academic medical center.
      PATIENT(S): Ninety-two patients failing to conceive after four ovulatory cycles
      with clomiphene citrate with a normal hysterosalpingogram who underwent
      laparoscopic evaluation of the pelvis. INTERVENTION(S): Laparoscopy. MAIN OUTCOME
      MEASURE(S): Presence of pelvic pathology and predictors of pelvic disease.
      RESULT(S): Of the 92 patients studied, 32 patients (34.8%) had a "positive"
      laparoscopy (i.e., stages III and IV endometriosis, an endometrioma, pelvic
      adhesions, and/or tubal disease), 27 patients (29.3%) had stage I or II
      endometriosis, and 30 patients (32.6%) had a normal pelvis. The predictors for
      intrapelvic disease were a history of dyspareunia, no prior use of oral
      contraceptive pills, and no prior use of any form of contraception. Almost 40% of
      women with predictors had a "positive" laparoscopy, compared with only 12.5% of
      patients without predictors; however, the majority of patients (91.3%) had at
      least one predictor. CONCLUSION(S): More than one third of the patients failing
      to conceive after four ovulatory cycles of clomiphene citrate had significant
      intrapelvic pathology. Although predictors for intrapelvic disease were isolated,
      their high prevalence reduced their predictive value.

PMID- 14667884
TI  - Fluctuation of 6Ckine expression in human endometrium during the menstrual cycle.
AB  - OBJECTIVE: To clarify the expression of 6Ckine, a potential chemoattractant for
      endometrial natural killer (NK) cells, in the human endometrium. DESIGN:
      Experimental study. SETTING: Department of obstetrics and gynecology at a medical
      university. PATIENT(S): Fifty-seven fertile women 25 to 52 years of age who had
      regular menstrual cycles and normal endometrium and were undergoing hysterectomy.
      INTERVENTION(S): Endometrium was obtained from operative samples. MAIN OUTCOME
      MEASURE(S): Tissue was immunostained to determine the localization of 6Ckine in
      the endometrium throughout the menstrual cycle. The number of NK cells was
      counted in 10 nonoverlapping stromal areas. The concentration of 6Ckine in
      homogenized endometrium was determined by enzyme-linked immunosorbent assay.
      RESULT(S): Endometrial surface, glandular epithelial cells, and perivascular
      stromal cells were immunoreactive for 6Ckine throughout the menstrual cycle with
      some fluctuation. In addition, some T cells, NK cells, and macrophages in the
      stroma were immunoreactive for 6Ckine. The 6Ckine concentration was low in the
      proliferative phase but elevated in the secretory phase. It showed a moderate
      positive correlation with the number of endometrial NK cells. CONCLUSION(S):
      6Ckine may be a potential chemoattractant for endometrial NK cells.

PMID- 14667885
TI  - Relationship between insulin resistance and gonadotropin dissociation in obese
      and nonobese women with polycystic ovary syndrome.
AB  - OBJECTIVE: To test the interdependence between insulin resistance (IR) and
      gonadotropin dissociation (GD) in polycystic ovary syndrome (PCOS). DESIGN: Cross
      sectional prospective study. SETTING: Clinical research center. PATIENT(S):
      Thirty-two PCOS patients aged 19-34 years; 16 obese (BMI > or = 27) and 16
      nonobese (BMI < 27). INTERVENTION(S): A 75-g oral glucose tolerance test (OGTT)
      and a 100-microg i.v. GnRH test were performed on different days. Blood was taken
      at 0, 30, 60, 90, 120, and 180 minutes in each test. Serum glucose, insulin, LH,
      and FSH were measured. MAIN OUTCOME MEASURE(S): Area under the curve was
      calculated for glucose, insulin, and glucose-to-insulin ratio (GIR), and for LH,
      FSH, and LH-FSH ratio. RESULT(S): Glucose, insulin, and GIR were not modified
      significantly during the GnRH test, nor LH, FSH and LH-FSH ratio throughout the
      OGTT. There were no significant differences in GIR response of patients with and
      without GD, nor in LH-FSH ratio of patients with and without IR, after OGTT and
      GnRH test. However, obese patients with IR had a significantly larger (P<.04)
      area under the curve for LH-FSH ratio than those without IR after GnRH test, but
      not after OGTT test. CONCLUSION(S): Insulin resistance and GD do not appear to be
      related events in PCOS, suggesting that each one might be determined by different
      genetic disorders. However, IR can affect GD after chronic stimulation in obese
      patients.

PMID- 14667886
TI  - Measurement of inhibin A and inhibin pro-alphaC in early human pregnancy and
      their role in the prediction of pregnancy outcome in patients with recurrent
      pregnancy loss.
AB  - OBJECTIVE: To examine the temporal relationship among inhibin A, beta-hCG, and
      pro-alphaC in early pregnancy and to determine whether the measurement of these
      hormones has any role in prediction of pregnancy outcome in patients with
      recurrent spontaneous miscarriage. DESIGN: Prospective descriptive study.
      SETTING: A tertiary referral center for recurrent miscarriage. PATIENT(S): Thirty
      six pregnant women with previous history of recurrent spontaneous pregnancy loss.
      INTERVENTION(S): Serial blood samples were collected prospectively at 6, 8, 10,
      and 12 weeks of gestation and were analyzed for inhibin A and inhibin pro-alphac
      using a two-site enzyme-linked immunosorbent assay as well as for beta-hCG using
      the microparticle enzyme immunoassay. MAIN OUTCOME MEASURE(S): Serum levels of
      inhibin A, inhibin pro-alphac, and beta-hCG. RESULT(S): The patients were
      allocated to two groups according to the pregnancy outcome: group 1 consisted of
      patients whose pregnancy continued beyond 20 weeks (control group); and group 2
      consisted of patients who spontaneously aborted (aborted group). There was a
      significant difference in inhibin A concentrations between the control and
      aborted groups at 8, 10, and 12 weeks' gestation. Significant differences in beta
      hCG concentrations between the two groups is evident only at 10 weeks' gestation.
      There were no significant differences in inhibin pro-alphac concentrations
      between the two groups at any gestational age. Assessment of the trend in the
      control group over the study period showed a significant increase in inhibin A
      and beta-hCG but not inhibin pro-alphac levels. CONCLUSION(S): Low serum levels
      of inhibin A at early gestational age in pregnancies destined to miscarry suggest
      a role for this glycoprotein as a marker for early pregnancy viability. Its
      measurement at the time of the first pregnancy test might be able to predict
      pregnancy outcome.

PMID- 14667887
TI  - Female sexual arousal: a behavioral analysis.
AB  - OBJECTIVE: This study was designed to assess female sexual arousal by using a
      combination of physiologic measures and self-reported level of arousal. DESIGN:
      Twenty subjects viewed a 23-minute sequence of randomly ordered relaxation and
      erotic tapes, both with and without auditory stimulus. The physiologic parameters
      of vaginal blood flow, galvanic skin resistance, respiration, pulse, and blood
      pressure, as well as self-reported level of arousal, were simultaneously recorded
      and correlated with video segments. SETTING: An academic teaching hospital.
      PATIENT(S): The 20 subjects (mean age +/- SD: 24.9 +/- 3.0 years) included
      Caucasian (10), Hispanic (2), Asian-American (4), and African-American (4) women.
      All women were screened for normal sexual function with the Female Sexual
      Function Index (FSFI) and with the Beck Anxiety Inventory and Beck Depression
      Inventory. INTERVENTION(S): Randomly ordered sequences of erotic and relaxation
      tapes with and without sound. MAIN OUTCOME MEASURE(S): Physiologic and behavioral
      data, as well as subjective arousal rating, were acquired. The resulting set of
      multichannel data was correlated with erotic segments and analyzed for sound vs.
      no sound and time to maximal physiologic arousal. RESULT(S): Four independent
      variables were found to have beta values that were significantly different from
      0: respiration (mean = -0.239, SD = 0.177, range = -0.55-0.09, t = -6.04), VPP
      (mean = 0.158, SD = 0.37, range = -0.48-0.80, t = 1.91), rVPP (mean = 0.161, SD =
      0.35, range = -0.537-0.686, t = 2.075), and erotic marker (mean = 0.582, SD =
      0.191, range = 0.16-0.85, t = 13.6). Neither heart rate nor galvanic skin
      resistance beta values approached significance. Respiration period was correlated
      negatively with arousal rating, indicating that subjects breathed faster when
      aroused. Auditory stimuli during erotic segments did not increase subjective
      arousal, and for both subjective arousal rating as well as VPP measurement,
      maximal response occurred within 2 minutes. CONCLUSION(S): Simultaneous
      measurement of vaginal blood flow, respiration, pulse, and a variable accounting
      for the onset and offset of erotic video segments accounts for approximately 50%
      of the variance in predicting subjective female arousal. Regardless of the
      presence or absence of audio input, 2 minutes was the average minimum time
      required to reach maximal arousal in young, sexually functional women.

PMID- 14667888
TI  - Uterine fibroids and gynecologic pain symptoms in a population-based study.
AB  - OBJECTIVE: To determine the association between dyspareunia, dysmenorrhea, and
      noncyclic pelvic pain and the presence and characteristics of uterine fibroids.
      DESIGN: Population-based cross-sectional study. SETTING: Desio, Italy.
      PATIENT(S): Six hundred thirty-five non-care-seeking participants of the Seveso
      Women's Health Study with an intact uterus who underwent transvaginal ultrasound.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ultrasound-detected presence of
      uterine fibroids and fibroid characteristics including volume, number, location,
      and position. Current dyspareunia, dysmenorrhea, and noncyclic pelvic pain was
      measured by self-report on a visual analog scale. RESULT(S): Uterine fibroids
      were detected in 96 women (15%). Women with fibroids were more likely to report
      moderate or severe dyspareunia (adjusted odds ratio [OR] = 2.8, 95% confidence
      interval [CI] = 0.9-8.3, statistically significant trend) and moderate or severe
      noncyclic pelvic pain (adjusted OR = 2.6, 95% CI = 0.9-7.6, statistically
      significant trend) than women without fibroids. Moderate or severe dysmenorrhea
      was not associated with the presence of fibroids (adjusted OR = 1.1, 95% CI = 0.5
      2.6). Number and total volume of fibroids were not related to pain.
      CONCLUSION(S): This is the first population-based study of gynecologic pain
      symptoms and fibroids. Dyspareunia and noncyclic pelvic pain, but not
      dysmenorrhea, increased in severity with the presence of uterine fibroids.
      Fibroid-associated pain symptomatology in a non-care-seeking population may be
      different from that of a clinic population.

PMID- 14667889
TI  - Long-term low-dose dehydroepiandrosterone oral supplementation in early and late
      postmenopausal women modulates endocrine parameters and synthesis of neuroactive
      steroids.
AB  - OBJECTIVE: To evaluate the effects of a low-dose DHEA supplementation on hormonal
      parameters in early and late postmenopausal women. DESIGN: Prospective case
      study. SETTING: Postmenopausal women in a clinical research environment.
      PATIENT(S): Twenty postmenopausal women were divided in two groups according to
      age (50-55 and 60-65 years). INTERVENTION(S): All patients underwent hormonal
      evaluation before and at 3, 6, 9, and 12 months of therapy (25 mg/d of DHEA
      orally). Pelvic ultrasound examination and Kupperman score were performed before
      and after 3, 6, and 12 months of therapy. MAIN OUTCOME MEASURE(S): Plasma DHEA,
      DHEAS, estrone (E1), E2, P, androstenedione (A), T, dihydrotestosterone, 17alpha
      hydroxyprogesterone (17-OHP), cortisol (F), allopregnanolone, beta-endorphin,
      sexual hormone-binding globulin (SHBG), LH, FSH, growth hormone (GH), and insulin
      like growth factor-1 (IGF-1) concentrations. RESULT(S): The levels of all the
      steroids that derive from DHEA metabolism increased in plasma with DHEA
      administration. Also neurosteroids (namely allopregnanolone) and endorphin showed
      increased plasma levels, whereas both gonadotropins were significantly reduced.
      Endometrial thickness did not change throughout the study period. CONCLUSION(S):
      Administration of low doses (25 mg) of DHEA positively modulates several
      endocrine parameters in early and late postmenopausal women, inducing the
      increase of the androgenic, estrogenic, and progestogenic milieu and reducing the
      climateric symptoms, similarly to estroprogestin replacement therapy. These data
      suggest that DHEA supplementation is a more effective replacement therapy than a
      simple "dietary supplement."

PMID- 14667890
TI  - Visualization of atypical hatching of a human blastocyst in vitro forming two
      identical embryos.

PMID- 14667891
TI  - Coincidental diagnosis of an occult hilar steroid cell tumor of the ovary and a
      cortisol-secreting adrenal adenoma in a 49-year-old woman with severe
      hyperandrogenism.
AB  - OBJECTIVE: To report an exceptional association between an occult ovarian steroid
      cell tumor and a cortisol-secreting adrenal adenoma. DESIGN: Case report.
      SETTING: Endocrinology and nutrition unit at a general hospital in Spain.
      PATIENT(S): A 49-year-old woman who presented with persistence of severe
      hyperandrogenism after removal of a left adrenal adenoma. INTERVENTION(S): An
      endocrine study evaluating serum androgens, adrenal function, and tumor markers
      was ordered. Transvaginal sonography was done to rule out an ovarian tumor.
      Finally, a selective catheterization of ovarian veins allowed the correct
      diagnosis. MAIN OUTCOME MEASURE(S): Clinical and endocrine description of the
      patient and preoperative localization of the source of T secretion. RESULT(S):
      After adrenal surgery, urinary free cortisol levels decreased to normal values,
      but serum T remained within the tumoral range (3.04 ng/mL). Selective
      catheterization of ovarian veins revealed a gradient of T concentration in the
      right ovary. After bilateral annexectomy, a microscopic steroid cell tumor of
      hilar type was found in the right ovary. Serum T fell within the normal range,
      and hirsutism progressively improved. CONCLUSION(S): This unusual association
      between an occult-virilizing ovarian steroid cell tumor and a cortisol-secreting
      adrenal adenoma illustrates the value of an accurate preoperative workup in women
      with severe hyperandrogenism.

PMID- 14667892
TI  - Use of a gonadotropin-releasing hormone antagonist for endometrial maturation and
      synchronization in an ovum recipient.
AB  - OBJECTIVE: To report the novel use of hMG and the GnRH antagonist for endometrial
      preparation and synchronization in a woman participating in an ovum donation
      program who was resistant to endometrial preparation with estrogen replacement.
      DESIGN: Case report. SETTING: Tertiary fertility center. PATIENT(S): The patient
      had inadequate endometrial maturation, as determined by pelvic ultrasound
      (thickness of <5 mm), after estrogen replacement. Ovarian hyperstimulation with
      hMG and a GnRH antagonist resulted in an endometrial thickness of 7.5 mm.
      Synchronization with a ovum donor resulted in a delivered twin gestation.
      INTERVENTION(S): : Late follicular transvaginal ultrasound. MAIN OUTCOME
      MEASURE(S): Appropriate endometrial maturation and pregnancy. RESULT(S):
      Appropriate endometrial maturation. CONCLUSION(S): For women with inadequate
      endometrial maturation with simple estrogen replacement, ovarian hyperstimulation
      with hMG and a GnRH antagonist can yield appropriate endometrial maturation for
      pregnancy through ovum donation.

PMID- 14667893
TI  - Assisted reproduction in patients with early-stage ovarian malignancies.
AB  - OBJECTIVE: To determine the outcome of women with early-stage ovarian
      malignancies who subsequently underwent assisted reproductive technologies (ART).
      DESIGN: Retrospective study. SETTING: Academic assisted reproductive technology
      program. PATIENT(S): Four infertile women who were previously diagnosed with
      early-stage ovarian malignancies. INTERVENTION(S): Controlled ovulation
      hyperstimulation, IVF, and/or gamete intrafallopian transfer treatments using
      clomiphene citrate and/or gonadotropins. MAIN OUTCOME MEASURE(S): Development of
      tumor recurrence and disease-free interval. RESULT(S): All four women remain free
      of disease for up to 15 years after treatment. Three of the four women achieved
      pregnancy. CONCLUSION(S): In patients with early-stage ovarian malignancies,
      conservative therapy followed by ovarian stimulation for assisted reproduction is
      an acceptable strategy.

PMID- 14667894
TI  - Willingness of volunteer blood donors to be volunteer semen donors.

PMID- 14667895
TI  - Endometrial volume as assessed by three-dimensional ultrasound is a predictor of
      pregnancy outcome after in vitro fertilization and embryo transfer.

PMID- 14667896
TI  - Increased concentration of vascular endothelial growth factor in the follicular
      fluid of patients with endometriosis does not affect the outcome of in vitro
      fertilization-embryo transfer.

PMID- 14667897
TI  - Use of clomiphene citrate in in vitro fertilization (IVF) and
      IVF/intracytoplasmic sperm injection cycles.

PMID- 14667898
TI  - The Glu298-->Asp polymorphism of the endothelial nitric oxide synthase gene is
      associated with endometriosis.

PMID- 14667899
TI  - Effect of intravaginal misoprostol use on uterine artery blood flow in patients
      with myoma uteri.

PMID- 14667900
TI  - Transport of embryos resulting from intracytoplasmic sperm injection, but not
      oocytes, adversely affects implantation.

PMID- 14667901
TI  - Prognostic value of embryo quality?

PMID- 14667903
TI  - hCG--mass units, molar conversions, and the standardization of biologic units.

PMID- 14667905
TI  - hCG--mass units, molar conversions, and the standardization of biologic units.

PMID- 14667906
TI  - Need bulletproof randomization.

PMID- 14667908
TI  - Estimating the efficacy of emergency contraception.

PMID- 14667909
TI  - Need bulletproof randomization.

PMID- 14667911
TI  - Trying to avoid bias in case-control and case-cohort studies.

PMID- 14667913
TI  - Trying to avoid bias in case-control and case-cohort studies.

PMID- 14667914
TI  - Hormonal contraception, immune responses, and pelvic inflammatory disease.

PMID- 14667916
TI  - Oversight, overlap, or not immediately relevant?

PMID- 14667917
TI  - Oversight, overlap, or not immediately relevant?

PMID- 14667919
TI  - Sexual dysfunction and sperm count--association?

PMID- 14667923
TI  - Revised minimum standards for practices offering assisted reproductive
      technologies.

PMID- 14667924
TI  - Mitochondrial biogenesis as a cellular signaling framework.
AB  - The identification, more than 50 years ago, of mitochondria as the site of
      oxidative energy metabolism has prompted studies that have unraveled the
      complexity of the numerous biosynthetic and degradative reactions, fundamental to
      cell function, carried out by these organelles. These activities depend on a
      distinctive mitochondrial structure, with different enzymes and reactions
      localized in discrete membranes and aqueous compartments. The characteristic
      mitochondrial structural organization is the product of both synthesis of
      macromolecules within the mitochondria and the import of proteins and lipids
      synthesized outside the organelle. Synthesis and import of mitochondrial
      components are required for mitochondrial proliferation, but rather than
      producing new organelles, these processes may facilitate the growth of pre
      existing mitochondria. Recent evidence indicates that these events are regulated
      in a complex way by several agonists and environmental conditions, through
      activation of specific transcription factors and signaling pathways. Some of
      these are now being elucidated. Generation of nitric oxide (NO) appears to be a
      novel player in this scenario, possibly acting as a unifying molecular switch to
      trigger the whole mitochondriogenic process.

PMID- 14667925
TI  - Comparative efficacy of novel platinum(IV) compounds with established
      chemotherapeutic drugs in solid tumour models.
AB  - Platinum(II)-based anticancer drugs are associated with high reactivity and thus
      a poor biological stability. The platinum(IV)-complexes display potential
      advantages due to their greater stability and bioreductive activation, thereby
      allowing a greater proportion of the drug to arrive at the target intact. All
      compounds tested were able to produce cytotoxicity in monolayer cell cultures,
      however, the potencies of platinum(IV) drugs were lower than that observed for
      the platinum(II) compounds or established organic chemotherapeutic agents. There
      was no significant alteration in the potency of platinum(II) or (IV) compounds to
      produce cytotoxicity in multicellular tumour spheroids (MCTS) compared to
      monolayer cultures. All the organic and platinum-based cytotoxic agents produced,
      to varying degrees, either a retardation or reduction in MCTS growth.
      Proliferating cells were restricted to the outer two to three cellular layers in
      intermediate (d=350 microm) and large (d=600 microm) MCTS. Regardless of MCTS
      size, drug treatment produced a larger and more widely distributed proliferating
      cell population, consistent with the recruitment of quiescent cells to the
      proliferating pool following cytotoxic damage. Histology indicated that the
      predominant morphological change was that of apoptosis, although there was some
      drug-dependent effects such as the metaphase arrest produced by vinblastine and
      chromatin dispersal to the periphery of nuclei produced by doxorubicin. In
      summary, whilst the platinum(IV) derivatives were able to produce cytotoxicity
      via apoptosis, the introduction of a stable axial group significantly retarded
      the rate at which this occurred.

PMID- 14667926
TI  - Glucuronidation as a mechanism of intrinsic drug resistance in colon cancer
      cells: contribution of drug transport proteins.
AB  - We have recently shown that drug conjugation catalysed by UDP
      glucuronosyltransferases (UGTs) functions as an intrinsic mechanism of resistance
      to the topoisomerase I inhibitors 7-ethyl-10-hydroxycamptothecin and NU/ICRF 505
      in human colon cancer cells and now report on the role of drug transport in this
      mechanism. The ability of transport proteins to recognise NU/ICRF 505 as a
      substrate was evaluated in model systems either transfected with breast cancer
      resistance protein 1 (Bcrp1), multidrug-resistance protein 2 (Mrp2) or Mrp3, or
      overexpressing MRP1 or P-170 glycoprotein. Results from chemosensitivity assays
      suggested that NU/ICRF 505 was not a substrate for any of the above proteins. In
      drug accumulation studies in human colon cancer cell lines NU/ICRF 505 was taken
      up avidly and retained in cells lacking UGTs (HCT116), whereas, following equally
      rapid uptake, it was cleared rapidly from cells displaying UGT activity (HT29) as
      glucuronide metabolites. HT29 cells were shown to express MRP1 and 3, but not P
      170 glycoprotein, MRP2 or breast cancer-resistance protein. The major glucuronide
      of NU/ICRF 505 inhibited ATP-dependent transport of estradiol 17-beta-glucuronide
      in Sf9 insect cell membrane vesicles containing MRP1 or MRP3, while co-incubation
      of HT29 cells with the MRP antagonist, MK571, significantly restored
      intracellular concentrations of NU/ICRF 505. These data lead us to conclude that
      the presence of a glucuronide transporter is essential for glucuronidation to
      represent a major de novo resistance mechanism and that UGTs will contribute more
      as a primary resistance mechanism when the parent drug (e.g. NU/ICRF 505) is not
      itself recognised by transport proteins.

PMID- 14667927
TI  - Mechanism of mahanine-induced apoptosis in human leukemia cells (HL-60).
AB  - Mahanine, a carbazole alkaloid occurs in the edible part of Micromelum minutum,
      Murraya koenigii and related species has been found to induce apoptosis in human
      myeloid cancer cell (HL-60). Concentration of 10 microM mahanine caused a
      complete inhibition of cell proliferation and the induction of apoptosis in a
      time dependent manner. Mahanine-induced cell death was characterized with the
      changes in nuclear morphology, DNA fragmentation, activation of caspase like
      activities, poly(ADP-ribose) polymerase cleavage, release of cytochrome c into
      cytosol and stimulation of reactive oxygen species generation. The cell death was
      completely prevented by a pancaspase inhibitor benzyloxycarbonyl-L-aspart-1-yl
      [(2,6-dichlorobenzoyl)oxy]methane (Z-Asp-CH(2)-DCB). Mahanine activated various
      caspases such as caspase-3, -6, -8 and -9 (like) activities but not caspase-1
      like activity. More than 70% cell survival was observed in the presence of a
      caspase-3 inhibitor. In addition, co-treatment of cyclosporin A markedly
      increased the survival of mahanine-treated HL-60 cells. Flow cytometric analysis
      revealed that mahanine decreased the mitochondrial membrane potential of intact
      cells, and disrupted cell cycle progression by increasing the number of cells in
      sub-diploid region, concomitantly with the decrease of cells in diploid phases,
      particularly at late hours of apoptosis. The overall results suggest that
      mahanine down regulates cell survival factors by activation of caspase-3 through
      mitochondrial dependent pathway, and disrupts cell cycle progression.

PMID- 14667928
TI  - Propolin C from propolis induces apoptosis through activating caspases, Bid and
      cytochrome c release in human melanoma cells.
AB  - We had demonstrated that two prenylflavanones, propolin A and propolin B,
      isolated and characterized from Taiwanese propolis, induced apoptosis in human
      melanoma cells and significantly inhibited xanthine oxidase activity. Here, we
      have isolated a third compound called propolin C. The chemical structure of
      propolin C has been characterized by NMR and HRMS spectra, and was identical to
      nymphaeol-A. However, no biological activities of this compound have ever been
      reported. In the present study, propolin C effectively induced a cytotoxic effect
      on human melanoma cells, with an IC(50) of about 8.5 microM. DNA flow cytometric
      analysis indicated that propolin C actively induced apoptosis in human melanoma
      cells and there is a marked loss of cells from the G2/M phase of the cell cycle.
      To address the mechanism of the apoptosis effect of propolin C, we evaluated the
      effect of propolin C on induction of apoptosis-related proteins in human melanoma
      cells. The levels of procaspase-8, Bid, procaspase-3, and poly(ADP-ribose)
      polymerase were decreased in dose- or time course-dependent manners. Moreover,
      propolin C was capable of releasing cytochrome c from mitochondria to cytosol.
      The findings suggest that propolin C may activate a mitochondria-mediated
      apoptosis pathway. On other hand, propolin C is a potential antioxidant agent and
      shows a strong capability to scavenge free radicals and inhibit on xanthine
      oxidase activity with IC(50) of about 17.0microM. In conclusion, the isolation
      and characterization of propolin C from bee propolis are described for the first
      time, and this compound is a powerful inducer of apoptosis in human melanoma
      cells.

PMID- 14667929
TI  - Anti-proliferation effect of 5,5-diphenyl-2-thiohydantoin (DPTH) in human
      vascular endothelial cells.
AB  - The aim of this study was to examine the anti-proliferation effect of 5,5
      diphenyl-2-thiohydantoin (DPTH), an analogue of antiepileptic drug phenytoin (5,5
      diphenylhydantoin), on human umbilical vein endothelial cells (HUVEC) and its
      possible molecular mechanism underlying. Here we demonstrated that DPTH at a
      range of concentrations (12.5-50 microM) dose- and time-dependently inhibited DNA
      synthesis and decreased cell number in cultured HUVEC, but not human fibroblasts.
      DPTH was not cytotoxic at these concentrations. [3H]Thymidine incorporation and
      flow cytometry analyses demonstrated that treatment of HUVEC with DPTH arrested
      the cell at the G0/G1 phase of the cell cycle. Western blot analysis revealed
      that the protein level of p21 increased after DPTH treated. In contrast, the
      protein levels of p27, p53, cyclins A, D1, D3 and E, cyclin-dependent kinase
      (CDK)2, and CDK4 in HUVEC were not changed significantly after DPTH treatment.
      Immunoprecipitation showed that the formations of the CDK2-p21 and CDK4-p21
      complex, but not the CDK2-p27 and CDK4-p27 complex, were increased in the DPTH
      treated HUVEC. Kinase assay further demonstrated that both CDK2 and CDK4 kinase
      activities were decreased in the DPTH-treated HUVEC. Pretreatment of HUVEC with a
      p21 antisense oligonucleotide reversed the DPTH-induced inhibition of
      [3H]thymidine incorporation into HUVEC. In conclusion, these data suggest that
      DPTH inhibits HUVEC proliferation by increasing the level of p21 protein, which
      in turn inhibits CDK2 and CDK4 kinase activities, and finally interrupts the cell
      cycle. The findings from the present study suggest that DPTH might have the
      potential to inhibit the occurrence of angiogenesis.

PMID- 14667930
TI  - Flavin-dependent antioxidant properties of a new series of meso-N,N'-dialkyl
      imidazolium substituted manganese(III) porphyrins.
AB  - A number of synthetic manganese complexes exhibit both in vitro and in vivo
      catalytic antioxidant activities. This study reports that the antioxidant
      potencies of a new series of meso-N,N'-dialkyl-imidazolium substituted
      manganese(III) porphyrins are dependent, in part, on their ability to redox cycle
      with endogenous flavin-dependent oxidoreductases. Inhibition of lipid
      peroxidation activities of these novel cationic porphyrins was compared using rat
      brain homogenate as a source of lipids and endogenous oxidoreductases. Iron and
      ascorbate was used as initiators of lipid peroxidation, and two indices of lipid
      peroxidation (thiobarbituric acid reactive species (TBARS) and F(2)-isoprostanes)
      were determined. All meso-N,N'-dialkyl-imidazolium substituted porphyrins tested
      were potent inhibitors of lipid peroxidation with IC(50) ranging from 0.1 to 34
      microM with a metal-dependent potency of Mn(III)>>Co(III)>Zn(II). A flavin
      dependent oxidoreductase antioxidant process was supported by the ability of the
      diphenyleneiodonium chloride (DPI, a flavoenzyme inhibitor) to decrease the
      potency of Mn-porphyrins in the lipid peroxidation model and that Mn-porphyrins
      stimulate NADPH oxidation in rat brain homogenates. These data suggest that
      metalloporphyrins may have differential antioxidant effects in tissues due to the
      presence or absence of flavin-dependent oxidoreductases.

PMID- 14667931
TI  - Medetomidine analogs as selective agonists for the human alpha2-adrenoceptors.
AB  - alpha(2)-Adrenoceptor (AR) agonists have therapeutic applications in a variety of
      diseases. Medetomidine, an alpha(2)-AR agonist, belongs to 4-substituted
      imidazole class of compounds and is highly selective for the alpha(2)-AR. The
      benzylic methyl group of medetomidine and naphthalene imidazole was proposed to
      interact with rat brain alpha(2)-ARs via a methyl binding pocket in a manner
      analogous to its presence in alpha-methyl norepinephrine. A series of derivatives
      containing hydrophilic and hydrophobic substituents, as well as chiral and
      conformationally rigid analogs were used. In current binding and functional
      studies using human alpha(2)-AR subtypes expressed in Chinese hamster ovary
      cells, optimal interactions were observed with the presence of the methyl group
      on the benzylic carbon atom of naphthyl imidazole. Data obtained with various
      analogs have demonstrated that size, electronegativity, lipophilicity, chirality
      and conformational flexibility of the substituents at the carbon bridge of
      naphthyl imidazole are important factors for interaction of the imidazole class
      of ligands with these alpha(2)-AR subtypes. Taken collectively, the results
      obtained support the existence of the methyl binding pocket for optimal ligand
      receptor binding interactions in human alpha(2)-AR subtypes. Further, the results
      also suggest that, additional modifications of medetomidine and naphthyl methyl
      imidazole at the benzylic carbon atom, and/or on the aromatic and imidazole ring
      systems could provide insights into the chemical requirements for optimizing
      alpha(2)-AR subtype selectivity. This could eventually lead to the discovery of
      promising compounds for the evaluation of the physiological importance of the
      three alpha(2)-AR subtypes.

PMID- 14667932
TI  - Effects of triaryl phosphates on mouse and human nuclear receptors.
AB  - The constitutively active receptor (CAR) is a crucial regulator of genes encoding
      for enzymes active in drug/steroid oxidation, conjugation, and transport. In our
      attempt to isolate the endogenous inhibitory ligand(s) for the mouse CAR, we
      found surprisingly that the inhibitory activity was associated with di- and tri
      isopropylated phenyl phosphates that were present in livers of untreated mice.
      Trans-activation experiments in mammalian cells with synthetic compounds verified
      that mouse CAR was inhibited by various isopropylated phenyl phosphates (40-80%).
      Such triaryl phosphates are widely used as fire retardants, lubricants, and
      plasticizers, and some of them are known to disturb reproduction by currently
      unknown mechanisms. Equipped with the finding that these compounds could interact
      with mouse CAR, we proceeded to determine their functional effects on other
      nuclear receptors. Human CAR and pregnane X receptor (PXR) were variably
      activated (2-5-fold) by triaryl phosphates while mouse PXR, peroxisome
      proliferator-activated receptor-alpha, and vitamin D receptor were refractory.
      Among steroid hormone receptors, the human androgen receptor was inhibited by
      triphenyl phosphate and di-ortho-isopropylated phenyl phosphate (40-50%) and
      activated by di- and tri-para-substituted phenyl phosphates (2-fold). Our results
      add to the list of CAR and PXR activators and suggest steroid-dependent
      biological pathways that may contribute to the reproductive effects of triaryl
      phosphates.

PMID- 14667933
TI  - Gene expression changes in rat liver following exposure to liver growth agents:
      role of Kupffer cells in xenobiotic-mediated liver growth.
AB  - Many xenobiotics are known to cause liver enlargement and hepatocarcinogenesis in
      rats, although the molecular mechanisms that underlie this effect remain largely
      undefined. Human exposure to several of these compounds, including
      glucocorticoids and peroxisome proliferators may be significant, due to their use
      in both pharmaceutical and industrial processes. It is therefore important to
      elucidate the molecular mechanisms underlying this abnormal liver enlargement in
      rats, as this will enable more accurate extrapolation of the possible outcomes of
      human exposure. Male Sprague-Dawley rats were dosed with the peroxisome
      proliferator Wy-14,643 and changes in liver gene expression examined using
      subtractive suppression hybridisation examined either 12 of 24hr later. Twenty
      five transcripts were identified which showed differential gene expression in
      liver following exposure to Wy-14,643. Biochemical indices of liver growth (DNA
      synthesis, apoptosis) showed that these changes correlated with the initiation of
      liver enlargement. Rats were next treated with either Wy-14,643, cyproterone
      acetate and dexamethasone, chemically and mechanistically-distinct hepatomegalic
      compounds. Carboxylesterase and Kupffer cell receptor mRNA levels were seen to
      alter in a qualitatively similar fashion for all three compounds, and in a liver
      specific fashion. In addition, these changes correlated with a decrease in the
      density of Kupffer cells within the liver, which are known to release mitogenic
      cytokines, and have been linked to Wy-14,643-induced cell proliferation. We
      therefore propose that Kupffer cells play a role in a general mechanism of
      xenobiotic-mediated liver enlargement.

PMID- 14667934
TI  - Inhibition of osteoclast formation by 3-methylcholanthrene, a ligand for
      arylhydrocarbon receptor: suppression of osteoclast differentiation factor in
      osteogenic cells.
AB  - We investigated the effects of 3-methylcholanthrene (3MC), a ligand for
      arylhydrocarbon receptor (AhR), on osteoclastogenesis. Osteoclast-like cells, in
      cocultures with mouse spleen cells and clonal osteogenic stromal ST2 cells, are
      formed from spleen cells by a combination of the receptor activator of nuclear
      factor-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF)
      produced by ST2 cells in response to 1alpha,25(OH)(2) Vitamin D(3). 3MC dose
      dependently inhibited the formation of mono- and multinuclear osteoclast-like
      cells. However, 3MC did not inhibit the formation of osteoclast-like cells from
      mouse spleen cells which was supported by the exogenous soluble RANKL and M-CSF.
      3MC did not affect the formation of an actin ring and pits on slices of dentine
      by osteoclast-like cells, both of which are typical indices of osteoclast
      activity. These results suggest that 3MC affects osteoclast-supporting cells such
      as ST2 cells but not osteoclast precursor cells and mature osteoclastic cells.
      When we measured the expression levels of RANKL mRNA in ST2 cells, 3MC dose
      dependently decreased the level of this mRNA. However, 3MC did not affect levels
      of mRNAs for osteoprotegerin (OPG), M-CSF, and the receptor of 1alpha,25(OH)(2)
      Vitamin D(3) in ST2 cells. Furthermore, soluble RANKL was able to counteract the
      inhibitory effect of 3MC on the formation of osteoclast-like cells. Our findings
      indicate that 3MC inhibits osteoclastogenesis via the inhibition of RANKL
      expression in osteoblastic cells.

PMID- 14667935
TI  - Adenosine A3 receptor-mediated regulation of p38 and extracellular-regulated
      kinase ERK1/2 via phosphatidylinositol-3'-kinase.
AB  - The adenosine A(3) receptor generally couples to the G(i) class of heterotrimeric
      G proteins, thereby decreasing cAMP levels and also mediating signaling via
      release of betagamma subunits. Here we describe the central role of
      phosphatidylinositol-3'-kinase (PI3K) for adenosine A(3) receptor-induced
      intracellular signaling to the stress-activated protein kinase p38 and the
      extracellular signal-regulated protein kinases ERK1/2. We used Chinese hamster
      ovary cells expressing the human adenosine A(3) receptor, phospho-specific
      antibodies and different pharmacological tools to dissect the signaling pathways
      involving PI3K. The adenosine receptor agonist 5'N-ethylcarboxamidoadenosine
      induced a time- and dose-dependent increase in p38 and ERK1/2 phosphorylation,
      two signaling pathways that appeared also to be activated in the immortalized
      microglia cell line N13, which expressed endogenous adenosine A(3) receptors. The
      5'N-ethylcarboxamidoadenosine-induced effects on p38 and ERK1/2 in CHO cells were
      blocked by pertussis toxin pretreatment and were sensitive to pharmacological
      inhibition of PI3K. In addition, inhibition of Rac/Cdc42, small GTPases of the
      Rho family, by clostridium toxin B, diminished p38 phosphorylation but did not
      affect ERK1/2. Furthermore, we identified the serine 727 site of signal
      transducer and activator of transcription STAT3 as a probable downstream target
      of ERK1/2, and thereby provide evidence that adenosine A(3) receptor mediated
      ERK1/2 activation has functional consequences.

PMID- 14667936
TI  - Rapid tyrosine phosphorylation of focal adhesion kinase, paxillin, and p130Cas by
      gastrin in human colon cancer cells.
AB  - Although the expression of CCK(2) receptors is widely reported in human
      colorectal cancers, little is known on its role in mediating the proliferative
      effects of mature amidated gastrin (G17 amide) on colorectal cancers. The purpose
      of the present study was to determine the effects of G17 amide on tyrosine
      phosphorylation of focal adhesion kinase (FAK), paxillin, and p130 Crk-associated
      substrate (p130(Cas)) in Colo 320 cells, a human colorectal cancer cell line
      which expresses CCK(2) receptors. By immunoprecipitation and immunoblotting, an
      increase in tyrosine phosphorylation of FAK (tyrosine-397), paxillin (tyrosine
      31), and p130(Cas) was detected in a time- and dose-dependent manner.
      Overexpression of CCK(2) receptors in Colo 320 cells (Colo 320 WT) by stable
      transfection with the human CCK(2) receptor cDNA resulted in an increased
      tyrosine phosphorylation of FAK, paxillin, and p130(Cas). After incubation with 1
      microM L-365,260, a specific CCK(2) receptor antagonist, this increase was
      completely inhibited. Our results demonstrate that in human colon cancer cells,
      gastrin caused a rapid tyrosine phosphorylation of FAK, paxillin, and p130(Cas)
      by activation of CCK(2) receptor. The phosphorylation of these proteins might be
      important in mediating gastrin effects on proliferation, apoptosis, and
      metastasis.

PMID- 14667937
TI  - Selective expression of Kir6.1 protein in different vascular and non-vascular
      tissues.
AB  - K(ATP) channels are composed of pore-forming subunits Kir6.x and auxiliary
      subunits SURx. These channels play important roles in modulating the
      contractility of vascular smooth muscle cells (SMCs) by altering membrane
      potentials. The molecular basis of K(ATP) channels in vascular SMCs is unclear
      and the expression of different K(ATP) channel subunits at protein level in
      various tissues still undetermined. In this study, using an anti-Kir6.1 antibody,
      we detected the expression of Kir6.1 proteins in rat vascular tissues including
      mesenteric artery, pulmonary artery, aorta, and tail artery. Kir6.1 proteins were
      also identified in heart and other non-vascular tissues including spleen and
      brain, but they were undetectable in liver and kidney. Immunocytochemical study
      revealed the expression of Kir6.1 proteins in cultured rat thoracic aortic SMCs.
      Using the whole-cell patch-clamp technique, it was found that the intracellularly
      applied anti-Kir6.1 antibody significantly inhibited K(ATP) channel currents in
      HEK-293 cells that were stably transfected with Kir6.1 cDNA. A better
      understanding of differential expression of Kir6.1 proteins in various vascular
      and non-vascular tissues may help discern different molecular basis and functions
      of K(ATP) channel complexes in these tissues.

PMID- 14667938
TI  - Lack of hypotriglyceridemic effect of gemfibrozil as a consequence of age-related
      changes in rat liver PPARalpha.
AB  - We have investigated if changes in hepatic lipid metabolism produced by old age
      are related to changes in liver peroxisome proliferator-activated receptor alpha
      (PPARalpha). Our results indicate that 18-month-old rats showed a marked decrease
      in the expression and activity of liver PPARalpha, as shown by significant
      reductions in PPARalpha mRNA, protein and binding activity, resulting in a
      reduction in the relative mRNA levels of PPARalpha target genes, such as liver
      carnitine-palmitoyl transferase-I (CPT-I) and mitochondrial medium-chain acyl-CoA
      dehydrogenase (MCAD). Further, in accordance with a liver PPARalpha deficiency in
      old rats, treatment of old animals with a therapeutic dose of gemfibrozil (GFB)
      (3mg/kg per day, 21 days) was ineffective in reducing plasma triglyceride
      concentrations (TG), despite attaining a 50% reduction in TG when GFB was
      administered to young animals at the same dose and length of treatment. We
      hypothesize that the decrease in hepatic PPARalpha can be related to a state of
      leptin resistance present in old animals.

PMID- 14667939
TI  - Inhibition of RANTES expression by indirubin in influenza virus-infected human
      bronchial epithelial cells.
AB  - The human bronchial epithelial cells are the primary sites of influenza virus
      infection. In this study, the effect of indirubin on the expression of the
      chemokine regulated on activation, normal T cell expressed and secreted (RANTES)
      by the influenza virus-infected H292 human epithelial cell line was examined. The
      expression of RANTES mRNA was analyzed using reverse transcription polymerase
      chain reaction and the concentration of RANTES production was determined by the
      enzyme-linked immunosorbent assay. At the non-cytotoxic concentrations, indirubin
      was found to reduce both the expression and production of RANTES in influenza
      A/NWS/33-infected H292 cells. Inhibition was also observed in influenza virus
      B/Lee-infected cells. Significant reduction of the expression of IL-8 was not
      observed after the infection. Indirubin-3'-oxime, a recently developed derivative
      with kinase inhibitory activity, also mediates a potent inhibitory effect on the
      expression of RANTES. The influenza virus infection-induced phosphorylation of
      the nuclear transcription NF-kB regulatory molecule IkBalpha and the p38 MAP
      kinase were also found to be inhibited by indirubin-3'-oxime. This finding
      suggests that indirubin is one of the components in the Chinese medicinal herbs
      Isatis indigotica and Strobilanthes cusia with immunomodulatory activity on the
      expression of RANTES.

PMID- 14667940
TI  - Protection against lipopolysaccharide-induced sepsis and inhibition of
      interleukin-1beta and prostaglandin E2 synthesis by silymarin.
AB  - Silymarin is known to have hepatoprotective and anticarcinogenic effects.
      Recently, anti-inflammatory effect of silymarin is attracting an increasing
      attention, but the mechanism of this effect is not fully understood. Here, we
      report that silymarin protected mice against lipopolysaccharide (LPS)-induced
      sepsis. In this model of sepsis, silymarin improved the rate of survival of LPS
      treated mice from 6 to 38%. To further investigate the mechanism responsible for
      anti-septic effect of silymarin, we examined the inhibitory effect of silymarin
      on interleukin-1beta (IL-1beta) and prostaglandin E2 (PGE2) production in
      macrophages. Silymarin dose-dependently suppressed the LPS-induced production of
      IL-1beta and PGE2 in isolated mouse peritoneal macrophages and RAW 264.7 cells.
      Consistent with these results, the mRNA expression of IL-1beta and cyclooxygenase
      2 was also completely blocked by silymarin in LPS-stimulated RAW 264.7 cells.
      Moreover, the LPS-induced DNA binding activity of nuclear factor-kappaB/Rel was
      also inhibited by silymarin in RAW 264.7 cells. Taken together, these results
      demonstrate that silymarin has a protective effect against endotoxin-induced
      sepsis, and suggest that this is mediated, at least in part, by the inhibitory
      effect of silymarin on the production of IL-1beta and PGE2.

PMID- 14667941
TI  - Inhibition of formyl-methionyl-leucyl-phenylalanine-stimulated respiratory burst
      in human neutrophils by adrenaline: inhibition of Phospholipase A2 activity but
      not p47phox phosphorylation and translocation.
AB  - The polymorphonuclear neutrophil (PMN)-respiratory burst plays a key role in host
      defense and inflammatory reactions. Modulation of this key neutrophil function by
      endogenous agents and the mechanisms involved are poorly understood. This study
      was designed to analyze the mechanisms involved in the effect of adrenaline on
      neutrophil superoxide anions production. Using the superoxide dismutase (SOD)
      inhibitable cytochrome c reduction assay, we report here that the beta-adrenergic
      agonist, adrenaline at physiologic concentrations (5-100 nM) inhibited formyl
      methionyl-leucyl-phenylalanine (fMLP)-stimulated but not phorbol-myristate
      acetate (PMA)-stimulated PMN superoxide anion production. The inhibitory effect
      of adrenaline runs in parallel with an increase in intracellular levels of cAMP
      which was reversed by the protein kinase A (PKA) inhibitor H-89, suggesting a
      role for PKA in mediating the inhibitory effect of adrenaline on fMLP-induced
      superoxide production. Adrenaline at physiological concentrations did not inhibit
      the fMLP-stimulated membrane translocation of the NADPH oxidase components
      p47phox and p67phox, nor the fMLP-stimulated phosphorylation of p47phox. However,
      adrenaline strongly depressed the activity of the cytosolic isoform of
      Phospholipase A(2) (cPLA(2)). We suggest that adrenaline inhibits fMLP induced
      superoxide production upstream of the NADPH oxidase via a mechanism involving PKA
      and cPLA(2).

PMID- 14667942
TI  - Evidence that unsaturated fatty acids are potent inhibitors of renal UDP
      glucuronosyltransferases (UGT): kinetic studies using human kidney cortical
      microsomes and recombinant UGT1A9 and UGT2B7.
AB  - Renal ischaemia is associated with accumulation of fatty acids (FA) and
      mobilisation of arachidonic acid (AA). Given the capacity of UDP
      glucuronosyltransferase (UGT) isoforms to metabolise both drugs and FA, we
      hypothesised that FA would inhibit renal drug glucuronidation. The effect of FA
      (C2:0-C20:5) on 4-methylumbelliferone (4-MU) glucuronidation was investigated
      using human kidney cortical microsomes (HKCM) and recombinant UGT1A9 and UGT2B7
      as the enzyme sources. 4-MU glucuronidation exhibited Michaelis-Menten kinetics
      with HKCM (apparent K(m) (K(m)(app)) 20.3 microM), weak substrate inhibition with
      UGT1A9 (K(m)(app) 10.2 microM, K(si) 289.6 microM), and sigmoid kinetics with
      UGT2B7 (S(50)(app)440.6 microM) Similarly, biphasic UDP-glucuronic acid (UDPGA)
      kinetics were observed with HKCM (S(50) 354.3 microM) and UGT1A9 (S(50) 88.2
      microM). In contrast, the Michaelis-Menten kinetics for UDPGA observed with
      UGT2B7 (K(m)(app) 493.2 microM) suggested that kinetic interactions with UGTs
      were specific to the xenobiotic substrate and the co-substrate (UDPGA). FA (C16:1
      C20:5) significantly inhibited (25-93%) HKCM, UGT1A9 or UGT2B7 catalysed 4-MU
      glucuronidation. Although linoleic acid (LA) and AA were both competitive
      inhibitors of 4-MU glucuronidation by HKCM (K(i)(app) 6.34 and 0.15 microM,
      respectively), only LA was a competitive inhibitor of UGT1A9 (K(i)(app) 4.06
      microM). In contrast, inhibition of UGT1A9 by AA exhibited atypical kinetics.
      These data indicate that LA and AA are potent inhibitors of 4-MU glucuronidation
      catalysed by human kidney UGTs and recombinant UGT1A9 and UGT2B7. It is
      conceivable therefore that during periods of renal ischaemia FA may impair renal
      drug glucuronidation thus compromising the protective capacity of the kidney
      against drug-induced nephrotoxicity.

PMID- 14667943
TI  - Retraction notice of a previous article published in Gait and Posture.

PMID- 14667944
TI  - Retraction of "Gait analysis and energy consumption of below-knee amputees
      wearing three different prosthetic feet" [Gait and Posture 12 (2000) 162-168].

PMID- 14667945
TI  - Medio-lateral motion of the center of mass during obstacle crossing distinguishes
      elderly individuals with imbalance.
AB  - This study was performed to investigate whether elderly patients with imbalance
      can be distinguished from healthy elderly subjects by comparing their whole body
      center of mass (COM) motion in the medio-lateral (M-L) direction during obstacle
      crossing. Nine healthy elderly adults and six elderly patients having complaints
      of 'dizziness' or 'unsteadiness' during walking (three with bilateral/unilateral
      vestibular weakness and three with unclear diagnosis) were recruited to perform
      unobstructed level walking and crossing of obstacles set to 2.5, 5, 10 and 15% of
      each subject's height. Kinematics of the COM was calculated using a weighted sum
      average of a 13-segment biomechanical model. There were no significant group
      differences for the temporal-distance gait parameters during all testing
      conditions. However, elderly patients with balance disorders demonstrated
      significantly greater and faster lateral motion of the COM when crossing over
      obstacles. These measurements distinguish elderly patients with imbalance from
      healthy elderly subjects. Furthermore, the increased M-L motion of the COM during
      obstacle crossing showed a positive correlation with an increased M-L range of
      motion of the swing foot trajectory. This increase in M-L motion indicates a
      compensatory adjustment in the swing foot trajectory to land the swing foot at an
      appropriate location that would establish a new base of support to counter the
      balance disturbance in the frontal plane.

PMID- 14667946
TI  - Head and trunk stabilization strategies during forward and backward walking in
      healthy adults.
AB  - The purpose of this study was to investigate the head and trunk equilibrium
      strategies while walking forwards and backwards under different conditions (eyes
      open vs. closed, hard vs. soft surface) in a sample of 11 consenting healthy
      adult subjects. Nine markers placed on the subject allowed us to record the
      kinematics of the head, spine and pelvis segments while walking. The data were
      acquired and analyzed using an optical TV-image processor (ELITE system). For
      each locomotor trial, the walking speed as well as the absolute angular
      dispersions and the anchoring indexes (AI) of six segments around the roll and
      pitch axes were calculated to assess the head and trunk equilibrium strategies. A
      three-way repeated measures analysis of variance was used to depict differences
      between the walking conditions. The results showed that the walking speed was
      affected by the locomotion tasks (P < 0.05) with values ranging from 1.10 +/-
      0.21 m s(-1) for natural conditions (walking forwards on a hard surface, eyes
      open) to 0.79 +/- 0.15 m s(-1) for the most unusual conditions (walking backwards
      on a foam support, eyes closed). In general, walking backwards reduced the
      angular dispersion of the spine segments while the absolute angular dispersions
      of the head and pelvis did not vary significantly with any factors (P > 0.05).
      The AI around the roll axis indicated good stabilization in space of the head and
      pelvis with high positive values and this stability increased while the subject
      was walking backwards on a soft surface (foam). By contrast, the spinal segments
      were predominantly stabilized on the underlying segment (negative AI), and this
      stabilization even increased when the subjects walked backwards on a soft
      surface. Increasing the locomotion difficulty thus induced a generally rigid ('en
      bloc') functioning of the spinal segments and increased effectiveness of the head
      and pelvis stabilization strategies in space, especially when walking backwards
      on a soft surface.

PMID- 14667947
TI  - Methods for calculating internal mechanical work: comparison using elite runners.
AB  - Two methods for calculating internal work-the absolute work method, based on
      changes in mechanical energy, and the absolute power method, based on the powers
      produced by the joint moments of force-were compared. The results from both
      methods were normalized to body mass and running speed to obtain the 'internal
      biomechanical cost' (IBC). The IBCs of normal running for eight runners were
      compared to their IBCs for four inefficient running styles. The absolute power
      method was able to detect the inefficient runs significantly more often than the
      absolute work method (chi2 = 3.22, P < 0.05). In addition, the absolute power
      method showed less variability quantifying both internal and external work. In
      conclusion, the absolute power method was judged the superior technique for
      quantifying mechanical energy costs of running.

PMID- 14667948
TI  - Coordination of axial rotation and step execution: deficits in Parkinson's
      disease.
AB  - To determine why parkinsonian patients (PP) present some difficulties to initiate
      locomotion, a diagonal step has been investigated in two tasks in five control
      subjects (CS) and in ten PP. In the first task, the subjects had to perform one
      diagonal step without change in their orientation (WR); in the second task, they
      had to perform one diagonal step with a body rotation in the step direction (RO).
      The defended hypothesis is that the gait initiation deficits in Parkinson disease
      are a consequence of their difficulties to coordinate al the component of a
      complex movement. The analysed parameters were the duration of the postural and
      movement phases, the step length and velocity, and the amplitude of the
      horizontal ground reaction forces during each phase. Compared to CS, the PP
      showed a lengthening of the postural phase, a decrease in the step length and
      velocity and a reduction of the horizontal forces. The comparisons between the
      performances obtained in the WR versus those obtained the RO show in CS that the
      performances remained unchanged, whereas in PP the performances were
      significantly more altered in the RO. It illustrates the specific deficit
      occurring in PP while performing complex tasks where coordination between several
      components has to be achieved simultaneously.

PMID- 14667949
TI  - Postural and movement adaptations by individuals with a unilateral below-knee
      amputation during gait initiation.
AB  - The present study examined the compensatory strategies adopted by individuals
      with a unilateral below-knee amputation (BKA) during gait initiation. Eleven
      individuals with a unilateral BKA and 11 able-bodied subjects initiated gait at
      three step length conditions (+0, +25 and +50% of preferred step length). A lead
      limb condition was also introduced, such that all participants were required to
      initiate gait with both their left and right limbs. For all step length and lead
      limb conditions, it was found that individuals with a unilateral BKA required
      more time to initiate gait, as compared with the able-bodied. This increase in
      movement duration was attributed to the stability and movement limitations of the
      prosthetic limb. On the other hand, by prolonging the task duration, these
      individuals were also able to employ a 'horizontal impulse' strategy, whereby
      they could create a similar magnitude of horizontal impulse as the able-bodied
      without the need to apply a large magnitude of peak antero-posterior (A-P) force.

PMID- 14667950
TI  - Characteristic gait kinematics in persons with lumbosacral myelomeningocele.
AB  - Thirty self-ambulatory children with mid-lumbar to low-sacral myelomeningocele
      who walked without aids and 21 control children were evaluated by three
      dimensional gait analysis. Characteristic kinematic patterns and parameters in
      the trunk, pelvis, hip, knee and ankle were analyzed with respect to groups with
      successive weakness of the ankle plantarflexor, ankle dorsiflexor, hip abductor,
      hip extensor and knee flexor muscles. Extensive weakness of the plantarflexors
      resulted in kinematic alterations in the trunk, pelvis, hip and knee and in all
      three planes seen as knee flexion, anterior pelvic tilt and trunk and pelvic
      rotation. Additional extensive weakness of the dorsiflexors made little
      difference in the walking strategy. Large kinematic alterations in all planes
      were observed where there was a large extent of additional weakness of the hip
      abductor but strength remaining in the hip extensors. In this group, gait was
      characterized by large lateral sway of the trunk, rotation of the trunk and
      pelvis, pelvic hike and increased extension of the knees. In the group with total
      poresis hip extensors but yet some knee flexion, gait was similar to the previous
      group but there was less sagittal plane movement greates and posterior trunk
      tilt. Gait analysis provides an understanding of the compensatory strategies
      employed in these patients. Clinical management can be directed towards
      stabilizing the lower extremities and accommodating large upper body motion to
      preserve this method of self-ambulation even in children who have considerable
      hip extensor and abductor weakness.

PMID- 14667951
TI  - Cross-validation of marker configurations to measure pelvic kinematics in gait.
AB  - External tracking of three-dimensional lumbar spine and pelvic oscillations is a
      method recently used in clinical gait analysis. This investigation validated the
      use of plate mounted marker configurations overlying the median sacral crest (S1)
      against single marker sets placed over the anterior and posterior superior iliac
      spine for the assessment of angular kinematic profiles of the pelvis during
      treadmill ambulation. Rotational pelvic movements of 12 asymptomatic male
      subjects were recorded by a 3D-ultrasonic measurement device using four single
      markers placed over the anterior and posterior superior iliac spine.
      Additionally, three external ultrasound markers were mounted on a rigid plate
      placed over S1. No significant differences (P > 0.05) for movement variability or
      range of motion between marker configurations could be obtained. It could be
      concluded that trucking of plate-mounted markers overlying S1 seems to be
      adequate for monitoring rotational pelvic motions in normal gait.

PMID- 14667953
TI  - An overview of infliximab, etanercept, efalizumab, and alefacept as biologic
      therapy for psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic skin disorder that affects approximately 2% of
      the US and European populations. One of the major focuses in psoriasis research
      has been the development of biologic therapies that provide selective,
      immunologically directed intervention with fewer adverse effects than traditional
      therapies. OBJECTIVE: The aim of this review was to summarize the progress of 4
      biologic agents available or under investigation for clinical use: infliximab,
      etanercept, efalizumab, and alefacept. METHODS: Relevant information was
      identified through a MEDLINE search of the literature (1966 to May 2003) using
      the terms biologic therapy, psoriasis, infliximab, etanercept, efalizumab, and
      alefacept. In addition, meeting posters from the American Academy of Dermatology
      (2003) and International Investigative Dermatology (2003) were reviewed and
      included if perceived to be reliable and relevant. RESULTS: In a Phase II trial
      of infliximab, the percentages of patients reaching > or =75% improvement from
      baseline in the psoriasis area and severity index (PASI 75) at week 10 were as
      follows: 6% with placebo (3/51), 72% with infliximab 3 mg/kg (71/98), and 88%
      with infliximab 5 mg/kg (87/99). In a Phase III study, 34% of patients receiving
      etanercept 25 mg SC twice weekly (55/162) achieved PASI 75 at 12 weeks and 44%
      (71/162) at 24 weeks. Also, 49% of those receiving etanercept 50 mg (81/164)
      achieved PASI 75 at 12 weeks, and 59% (97/164) at 24 weeks. In 2 Phase III trials
      with SC efalizumab 1.0 mg/kg or 2.0 mg/kg or placebo, 30% in the 1.0-mg/kg per
      week group (117/394) achieved PASI 75; in the 2.0-mg/kg per week group, 28%
      (113/409) did. In the placebo, 3.4% (10/292) achieved PASI 75. In a Phase III
      trial of IM alefacept 15 mg once weekly for 12 weeks, IM alefacept 10 mg once
      weekly for 12 weeks, or placebo, 21% of the 15-mg dose group (35/166) achieved
      PASI 75 at 2 weeks after the last dose, compared with 5% of the placebo group
      (8/168). In a Phase III study of the efficacy and tolerability of once-weekly
      alefacept 7.5 mg via IV bolus, 14% (53/367) and 4% (7/186) of patients receiving
      alefacept and placebo achieved PASI 75 at week 14, respectively. Among those who
      received 2 courses of alefacept, 40% (73/183) and 71% (130/183) achieved PASI 75
      and > or = 50% improvement in PASI, respectively. All 4 drugs have been generally
      well tolerated. CONCLUSIONS: In the patients treated to date, infliximab,
      etanercept, efalizumab, and alefacept have achieved successful therapy of
      psoriasis without the organ toxicity seen with traditional systemic therapies.
      Potential limitations in the use of these agents include the expected high costs
      of treatment, lack of long-term follow-up, and the selective nature of the
      patient populations treated thus far.

PMID- 14667954
TI  - Newer antiepileptic drugs: possible uses in the treatment of neuropathic pain and
      migraine.
AB  - BACKGROUND: Both neuropathic pain and migraine are now being treated with a
      variety of newer antiepileptic drugs (AEDs). The proven efficacy of gabapentin in
      postherpetic neuralgia (PHN) and painful diabetic neuropathy (PDN), and of
      divalproex sodium in the prevention of migraine has led to increased clinical
      investigation of the newer AEDs for these conditions. While basic and clinical
      research are expanding the knowledge base concerning the fundamental mechanisms
      of neuropathic pain and migraine, growing recognition of the similarities in the
      pathophysiology of epilepsy, migraine, and various chronic pain disorders has
      further heightened interest in exploring the newer AEDs in the treatment of these
      conditions. OBJECTIVE: The goals of this article were to review the empiric basis
      and scientific rationale for the use of AEDs in the treatment of neuropathic pain
      and migraine; summarize available clinical research on the use of 5 newer AEDs
      (gabapentin, lamotrigine, oxcarbazepine, topiramate, and zonisamide) in these
      conditions; and provide a summary comparison of the dosing, tolerability, and
      drug-interaction potential of these agents. METHODS: Relevant English-language
      articles were identified through searches of MEDLINE (1990-March 2003), American
      Academy of Neurology abstracts (1999-2003), and American Epilepsy Society
      abstracts (2000-2002). The search terms were antiepileptic medication or drug,
      migraine headache, neuropathic pain, pathophysiology, treatment, mechanism of
      action, gabapentin, lamotrigine, oxcarbazepine, topiramate, and zonisamide.
      CONCLUSIONS: The newer AEDs possess the potential advantages of better
      tolerability and fewer drug-drug interactions compared with standard treatments
      such as tricyclic antidepressants or established AEDs. However, with the
      exception of data supporting the efficacy of gabapentin in PHS and PDN, there is
      currently insufficient evidence to determine whether the newer AEDs have equal or
      superior efficacy relative to proven pharmacotherapies.

PMID- 14667955
TI  - Double-masked, randomized, placebo-controlled clinical study of the mast cell
      stabilizing effects of treatment with olopatadine in the conjunctival allergen
      challenge model in humans.
AB  - OBJECTIVE: The purpose of this study was to assess the effects of olopatadine on
      the release of mast cell-derived mediators after conjunctival allergen
      challenge(CAC) in humans. METHODS: This was a double-masked, randomized, placebo
      controlled clinical trial. Subjects with a clinical history of seasonal allergic
      conjunctivitis (but no current symptoms or treatment at baseline) were studied.
      At visit 1, subjects underwent bilateral CAC with increasing doses of allergen
      every 15 minutes until a significant clinical reaction was obtained, then were
      evaluated at 15 minutes and 5 hours after CAC. At visit 2 (2 weeks later),
      subjects were rechallenged to confirm the allergic response. Subjects exhibiting
      positive reactions at both visits (at both 15 minutes and 5 hours) were
      randomized and instructed to treat 1 eye with olopatadine and the contralateral
      eye with placebo (commercially available artificial ears) in a double-masked
      fashion twice daily for the 5 days immediately preceding visit 3. At visit 3,
      bilateral CAC was performed with the same dose as at visit 2. Itching and redness
      were recorded. Tear cytology for inflammatory cell counts(ie, neutrophils,
      eosinophils, and lymphocytes) was carried out using precolored slides, and cell
      numbers were counted at 400x magnification. Tear histamine was assessed using
      radioimmunoassay histamine measurement. Intercellular adhesion molecule (ICAM)
      1/CD54 monoclonal antibody was used for immunohistochemical staining of
      conjunctival epithelial cells obtained by impression cytology. Slides were
      examined by 3 masked investigators and redness was classified on a scale of 0
      (absent) to 3 (very intense). RESULTS: Ten subjects completed the trial.
      Olopatadine significantly reduced postchallenge itching and redness compared with
      placebo (P < 0.01 and P < 0.03,respectively). Olopatadine also reduced the number
      of neutrophils and the total number of cells at 30 minutes (both P = 0.015), and
      the number of eosinophils(P < 0.001), neutrophils (P < 0.004), lymphocytes (P =
      0.011), and total number of cells (P = 0.001) at 5 hours postchallenge compared
      with placebo. Tear histamine levels were significantly lower after challenge in
      the eyes pretreated with olopatadine compared with placebo (mean [SD], 7 [8] vs
      22 [12] nmol/L; P = 0.04). Olopatadine significantly reduced tear histamine
      levels compared with those measured in the same eyes after CAC at visit 2 (P =
      0.001), whereas placebo did not affect histamine levels. Olopatadine also
      significantly reduced ICAM-1 expression compared with placebo at 30 minutes and 5
      hours postchallenge(P < 0.03 and P < 0.01, respectively). CONCLUSION: In the
      present study, olopatadine significantly reduced the levels of histamine,
      cellular infiltrate, and ICAM expression compared with placebo after CAC,
      suggesting that it reduced the release of mast cell-derived mediators in humans.
      This inhibition of mediator release correlated with reduction of itching and
      redness.

PMID- 14667956
TI  - Absolute oral bioavailability of rosuvastatin in healthy white adult male
      volunteers.
AB  - BACKGROUND: Rosuvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A-reductase
      inhibitor developed for the treatment of dyslipidemia. The results of clinical
      trials suggest that it is effective and well tolerated. OBJECTIVES: The goals of
      this study were to determine the absolute bioavailability of an oral dose of
      rosuvastatin and to describe the intravenous pharmacokinetics of rosuvastatin in
      healthy volunteers. METHODS: This was a randomized, open-label, 2-way crossover
      study consisting of 2 trial days separated by a > or =7-day washout period.
      Healthy male adult volunteers were given a single oral dose of rosuvastatin 40 mg
      on one trial day and an intravenous infusion of rosuvastatin 8 mg over 4 hours on
      the other. Pharmacokinetic and tolerability assessments were conducted up to 96
      hours after dosing. A 3-compartment pharmacokinetic model was fitted to the
      plasma concentration-time profiles obtained for each volunteer after intravenous
      dosing. RESULTS: Ten white male volunteers entered and completed the trial. Their
      mean age was 35.7 years (range, 21-51 years), their mean height was 177 cm
      (range, 169-182 cm), and their mean body weight was 77.6 kg (range, 68-85 kg).
      The absolute oral bioavailability of rosuvastatin was estimated to be 20.1%,and
      the hepatic extraction ratio was estimated to be 0.63. The mean volume of
      distribution at steady state was 134 L. Renal clearance accounted for
      approximately 28% of total plasma clearance (48.9 L/h). Single oral and
      intravenous doses of rosuvastatin were well tolerated in this small number of
      healthy male volunteers. CONCLUSIONS: The absolute oral bioavailability of
      rosuvastatin in these 10 healthy volunteers was approximately 20%, and absorption
      was estimated to be 50%. The volume of distribution at steady state was
      consistent with extensive distribution of rosuvastatin to the tissues. The modest
      absolute oral bioavailability and high hepatic extraction of rosuvastatin are
      consistent with first-pass uptake into the liver after oral dosing. Rosuvastatin
      was cleared by both renal and nonrenal routes; tubular secretion was the
      predominant renal process.

PMID- 14667957
TI  - Pharmacokinetic and pharmacodynamic properties of eptifabatide in healthy
      subjects receiving unfractionated heparin or the low-molecular-weight heparin
      enoxaparin.
AB  - BACKGROUND: The rationale for the combined use of glycoprotein (GP) IIb/Illa
      inhibitors, such as eptifibatide, and antithrombin agents, such as unfractionated
      heparin (UFH), in patients presenting with non-ST-segment elevation (NSTE) acute
      coronary syndrome (ACS) and those scheduled for percutaneous coronary
      intervention is based on the fact that these therapies target the complementary
      pathophysiologic mechanisms responsible for ischemic adverse effects. The results
      of a recent study indicated that the combination of eptifibatide and enoxaparin
      is associated with a reduced rate of ischemic adverse effects compared with the
      combination of eptifibatide and UFH. Therefore, the coadministration of
      eptifibatide with enoxaparin is an attractive option for the management of
      patients with NSTE ACS. OBJECTIVE: This study was designed to determine whether
      the substitution of enoxaparin for UFH, when coadministered with eptifibatide,
      affects the pharmacokinetic and pharmacodynamic properties of eptifibatide.
      METHODS: This open-label, crossover study was conducted at the Quintiles Clinical
      Pharmacology Unit (Lenexa, Kansas). Healthy subjects were sequentially treated
      with the GP IIb-IIIa inhibitor eptifibatide (180 microg/kg bolus + 2.0
      microg/kg.min infusion) plus UFH or eptifibatide plus the low-molecular-weight
      heparin enoxaparin, on 2 occasions, separated by a 6- to 14-day washout period.
      The order of administration of the 2 regimens was random. The primary end point
      of the study was the steady-state plasma concentration of eptifibatide (Css);
      secondary end points included the inhibition of platelet aggregation, area under
      the plasma-concentration time curve, apparent volume of distribution, plasma
      elimination half-life (t 1/2), and total body eptifibatide clearance (Cl).
      RESULTS: A total of 14 subjects (10 men, 4 women; mean [SD] age, 53.2 [6.0]years)
      were enrolled. The mean (SD) Css of eptifibatide was essentially identical when
      it was coadministered with either UFH or enoxaparin (1640 [227] ng/mL and 1610
      (229) ng/mL, respectively). In addition, no clinically significant differences
      were found between the coadministration of UFH versus enoxaparin in platelet
      aggregation inhibition, t 1/2, eptifibatide Cl, or other pharmacokinetic
      parameters. Both regimens were well tolerated; no serious adverse effects were
      reported. CONCLUSION: The results in this population of healthy subjects, age
      matched to the intended target population, suggest that eptifibatide can be used
      in the treatment of NSTE ACS effectively, with good tolerability, and without
      dose adjustment when coadministered with enoxaparin instead of with UFH.

PMID- 14667958
TI  - A randomized trial of laypersons' perception of the benefit of osteoporosis
      therapy: number needed to treat versus postponement of hip fracture.
AB  - BACKGROUND: Information on the benefits of therapeutic interventions can be ex
      pressed in various ways, including relative risk reduction, absolute risk
      reduction,and number needed to treat (NNT). An alternative to such risk-based
      measures is postponement of an adverse outcome (eg, hip fracture in the case of
      osteoporosis). OBJECTIVE: The goal of this study was to examine whether
      laypersons' perception of the benefit of an osteoporosis therapy differs when it
      is presented in terms of the NNT to avoid 1 hip fracture compared with the
      duration of postponement of hip fracture. METHODS: This was a cross-sectional,
      randomized, controlled trial. Face-to-face interviews of a representative sample
      of the Danish population were conducted in respondents' homes. Respondents were
      randomized to receive information about the benefits of a hypothetical
      osteoporosis intervention either in terms of different magnitudes of NNT (10, 50,
      100, or 400) or different durations of postponement of hip fracture (1 month, 6
      months, 1 year, or 4 years). Participants were subsequently asked if they would
      consent to the intervention. RESULTS: A total of 1728 individuals were contacted
      at home and asked if they would take part in a face-to-face interview; 967 (56%)
      were successfully interviewed. The age (mean age, 44.5 years; range, 20-74 years)
      and sex distribution (51% male, 50% female) of the sample was similar to that of
      the general Danish population. Based on NNTs of 10, 50, 100, and 400, the
      proportions of respondents who said they would consent to the intervention were a
      respective 65%,61%, 63%, and 57%. Increasing NNT was not significantly associated
      with a lower proportion of consent (test for trend chi-square(1)= 0.75; P = NS).
      Forty-three percent of respondents indicated that the concept of NNT was
      difficult to understand, and 38% interpreted NNT in a way that was probably
      incorrect. In terms of postponement of hip fracture by 1 month, 6 months, 1 year,
      and 4 years, the proportions who said they would consent to the intervention were
      a respective 25%, 40%, 39%, and 53%. Increasing postponement of hip fracture was
      significantly associated with higher proportions of consent (test for trend chi
      square(1)= 20.09;P < 0.001). Logistic regression analysis found that consenting
      to therapy was inversely associated with age (NNT: OR, 0.83; 95% CI, 0.72-0.96;
      postponement of fracture: OR, 0.84; 95% CI, 0.73-0.98) and with the magnitude of
      benefit presented in terms of postponement of fracture. No other variables were
      significantly associated with consent to therapy. CONCLUSIONS: When laypersons
      were presented with brief information about the benefit of a hypothetical
      osteoporosis intervention and were then offered this therapy, their choices were
      sensitive to the magnitude of treatment benefit when it was presented in terms of
      postponement of hip fracture but not in terms of NNT. These findings suggest that
      it may be easier for laypersons to understand a potential treatment benefit in
      terms of postponement of fracture rather than NNT.

PMID- 14667959
TI  - Tolerability and effects on quality of life of twice-daily extended-release
      carbamazepine in adults with seizure disorders: an open-label, 12- to 36-month
      continuation study.
AB  - BACKGROUND: An earlier 6-month, multicenter, open-label study in patients with
      complex partial seizures found that a switch from multiple daily doses of
      conventional carbamazepine (CBZ) to twice-daily CBZ extended-release capsules(CBZ
      ERC) was well tolerated, with maintenance of seizure control over the study
      period and significant improvements in quality of life (P < 0.001). OBJECTIVE:
      The goal of the present study was to assess the tolerability and effects on
      quality of life of twice-daily CBZ-ERC over the longer term in patients with
      seizure disorders. METHODS: This was a multicenter, open-label assessment of the
      long-term(12-36 months) tolerability and quality-of-life effects of twice-daily
      CBZ-ERC given at a daily dose equivalent to the daily dose of CBZ taken before
      study en-try. The regimen could be adjusted as clinically indicated up to a daily
      dose of 1600 mg. Patients could receive up to 2 other antiepileptic drugs during
      the study. RESULTS: One hundred eighteen patients were enrolled. In patients
      completing>12 months of study therapy, a significant decrease in the highest mean
      2-day frequency of generalized tonic-clonic seizures was observed over the first
      12 months (P = 0.005). The significant improvements in quality of life achieved
      in the earlier study were maintained during the present study. Of 37 patients who
      were discontinued from the study, 9 met criteria mandating withdrawal from the
      study due to exacerbation of seizures. Three patients were discontinued from the
      study for adverse events judged to be unrelated to study drug. Low incidences of
      rash (3.4%) and weight gain (0.8%) were reported. CONCLUSIONS: In this population
      of adults with seizure disorders, CBZ-ERC twice daily was well tolerated during
      12 to 36 months of open-label treatment,with no increase in seizure frequency or
      decrease in quality of life.

PMID- 14667960
TI  - Use of gabapentin for postherpetic neuralgia: results of two randomized, placebo
      controlled studies.
AB  - BACKGROUND: Postherpetic neuralgia (PHN), which affects up to 70% of elderly
      persons with herpes zoster, can have debilitating effects, including physical and
      social disability and significant psychological distress. A variety of agents
      have been used, either singly or in combination, to control PHN, including
      topical and oral analgesics, antidepressants, and antiepileptic drugs (AEDs).
      However, PHN often proves refractory to these therapies. OBJECTIVE: This article
      reviews available data on the use of the newer AED gabapentin for the control of
      PHN. METHODS: A MEDLINE search was undertaken to identify all randomized, placebo
      controlled trials on the use of gabapentin in PHN. The search terms were
      gabapentin and postherpetic neuralgia. RESULTS: The literature search identified
      2 published studies of the efficacy of gabapentin in a total of 563 patients with
      PHN that had persisted for at least 3 months after the healing of herpes zoster
      rash. The studies employed multiple outcome measures, including visual analog and
      Likert scales for pain intensity, and quality-of-life and functional measures
      that included the Medical Outcomes Study 36-item Short Form Health Survey (SF-36)
      and the Profile of Mood States. At maximum target dosages of 1800 to 3600 mg/d,
      gabapentin produced significant reductions in mean daily pain scores compared
      with placebo on both visual analog(P < 0.001) and Likert scales (P < 0.01).
      Improvements were also seen on the SF-36 subscales for physical functioning,
      bodily pain, vitality, and mental health(P < 0.01). CONCLUSION: Gabapentin may
      provide benefits in terms of alleviation of pain and overall quality of life in
      patients with chronic PHN.

PMID- 14667961
TI  - A Medicare Rx benefit: so close and yet so far.

PMID- 14667962
TI  - Epidemiologic impact and cost-effectiveness of universal infant vaccination with
      a 7-valent conjugated pneumococcal vaccine in the Netherlands.
AB  - BACKGROUND: Streptococcus pneumoniae is one of the main causes of bacterial
      meningitis, bacteremia, pneumonia, and otitis media in the Netherlands. These
      diseases lead to substantial mortality, morbidity, and costs. The societal impact
      is especially severe because most cases occur in very young infants. OBJECTIVE:
      The aim of this study was to estimate the epidemiological impact and cost
      effectiveness of universal infant vaccination with a 7-valent conjugated
      pneumococcal vaccine in the Netherlands. METHODS: Decision analysis was performed
      using epidemiological data and data on health care resource use from 1996 to
      2001. A model was used to project the impact of pneumococcal vaccination on the
      incidence of pneumococcal infections in infants and children from birth to age 10
      years. Costs, benefits, and health gains were estimated, and cost-effectiveness
      was calculated. All analyses were performed from a societal perspective. RESULTS:
      On average, 339 cases per year of invasive pneumococcal infection occurred in
      infants and children from birth to age 10 years in the Netherlands from 1996 to
      2001. The model predicted that introduction of the 7-valent conjugated
      pneumococcal vaccine would prevent 48 cases of bacterial meningitis and 88 cases
      of pneumococcal bacteremia per year, as well as 42,695 cases of pneumococcal
      otitis media and 3411 cases of invasive pneumococcal pneumonia. The model also
      predicted that vaccination would save 13 lives per year and prevent 31 cases of
      lifelong sequelae, rendering 382 discounted quality-adjusted life-years (QALYs)
      gained or 329 discounted life-years gained per year. Considering these health
      gains, vaccination would prevent Euro 9,453,600 of direct and indirect medical
      costs of meningococcal and pneumococcal infections in the Netherlands, including
      acute medical care, management of sequelae, and lost time at work. With a vaccine
      price of Euro 40 per dose, the base-case cost-effectiveness ratio would be Euro
      71,250 per QALY. The model was sensitive to changes in incidence of infections,
      vaccine effectiveness, and vaccine price. CONCLUSIONS: Our analytic model
      predicted that universal pneumococcal vaccination of infants in the Netherlands
      could prevent a large number of pneumococcal infections and considerably reduce
      related mortality and morbidity. However, the baseline cost-effectiveness ratio
      of such a vaccination program would be relatively unfavorable compared with other
      interventions implemented in the Netherlands.

PMID- 14667963
TI  - Effects of simvastatin and atorvastatin in hypercholesterolemic patients.

PMID- 14667965
TI  - Proceedings of the Second International Symposium on Progestins, Progesterone
      Receptor Modulators and Progesterone Antagonists. November 20-23, 2002. Siena,
      Italy.

PMID- 14667966
TI  - Progesterone receptor transcription and non-transcription signaling mechanisms.
AB  - The diverse effects of progesterone on female reproductive tissues are mediated
      by the progesterone receptor (PR), a member of the nuclear receptor family of
      ligand-dependent transcription factors. Thus, PR is an important therapeutic
      target in female reproduction and in certain endocrine dependent cancers. This
      paper reviews our understanding of the mechanism of action of the most widely
      used PR antagonist RU486. Although RU486 is a competitive steroidal antagonist
      that can displace the natural hormone for PR, it's potency derives from
      additional "active antagonism" that involves inhibiting the activity of PR
      hormone agonist complexes in trans through heterodimerization and competition for
      binding to progesterone response elements on target DNA, and by recruitment of
      corepressors that have the potential to actively repress gene transcription. An
      additional functional role for PR has recently been defined whereby a
      subpopulation of PR in the cytoplasm or cell membrane is capable of mediating
      rapid progesterone induced activation of certain signal transduction pathways in
      the absence of gene transcription. This paper also reviews recent results on the
      mechanism of the extra-nuclear action of PR and the potential biological roles
      and implications of this novel PR signaling pathway.

PMID- 14667967
TI  - Progesterone-dependent regulation of female reproductive activity by two distinct
      progesterone receptor isoforms.
AB  - The steroid hormone, progesterone, is a central coordinator of all aspects of
      female reproductive activity. The physiological effects of progesterone are
      mediated by interaction of the hormone with specific intracellular progesterone
      receptors (PRs) that are expressed from a single gene as two protein isoforms and
      that are members of the nuclear receptor superfamily of transcription factors.
      Analysis of the structural and functional relationships of each isoform using in
      vitro systems has demonstrated that the PR-A and PR-B proteins have different
      transcription activation properties when liganded to progesterone. More recently,
      selective ablation of the PR-A and PR-B proteins in mice had facilitated
      examination of the contribution of the individual PR isoforms to the pleiotropic
      reproductive activities of progesterone. Analysis of the phenotypic consequences
      of these mutations on female reproductive function has provided proof of concept
      that the distinct transcriptional responses to PR-A and PR-B observed in cell
      based transactivation assays are reflected in a distinct tissue-selective
      contribution of the individual isoforms to the reproductive activities of
      progesterone. In PR-A knock-out mice, in which the expression of the PR-A isoform
      is selectively ablated (PRAKO), the PR-B isoform functions in a tissue-specific
      manner to mediate a subset of the reproductive functions of PRs. Ablation of PR-A
      does not affect response of the mammary gland or thymus to progesterone but
      results in severe abnormalities in ovarian and uterine function leading to female
      infertility. More recent studies using PR-B knock-out (PRBKO) mice have shown
      that ablation of PR-B does not affect either ovarian, uterine or thymic responses
      to progesterone but results in reduced mammary ductal morphogenesis and
      alveologenesis during pregnancy. Thus, PR-A is both necessary and sufficient to
      elicit the progesterone-dependent reproductive responses necessary for female
      fertility, while the PR-B isoform is required to elicit normal proliferative and
      differentiative responses of the mammary gland to progesterone. This review will
      summarize our current understanding of the selective contribution of the two PR
      isoforms to progesterone action.

PMID- 14667968
TI  - Progesterone involvement in breast development and tumorigenesis--as revealed by
      progesterone receptor "knockout" and "knockin" mouse models.
AB  - In light of recent clinical trials, the debate concerning the risks and benefits
      of progestin-based postmenopausal hormone replacement therapy (HRT) has reached a
      renewed level of urgency. Irrespective of the position taken, the consensus is
      that more basic research needs to be performed to address progesterone's
      fundamental role in mammary development and tumorigenesis. Towards this end, the
      progesterone receptor knockout (PRKO) mouse demonstrated that progesterone is
      essential for pregnancy-associated mammary gland ductal side-branching and
      alveologenesis and that these morphological changes are dependent on progesterone
      induced mammary epithelial proliferation. Importantly, the PRKO mouse showed that
      the progesterone-proliferative signal significantly contributes to mammary tumor
      susceptibility in an established mammary tumor model. Insight into the cellular
      mechanism(s) by which progesterone affects mammary morphogenesis has been
      disclosed by a new PR-LacZ knockin mouse, which revealed that PR's spatial
      expression pattern undergoes precise choreographed distributional changes that
      precede key stages in postnatal mammary development. In the case of early
      pregnancy, the segregation of cells undergoing progesterone-induced proliferation
      from those that express PR implicates a paracrine mode of action for progesterone
      induced mammary epithelial proliferation, whereas the preparturient decline of PR
      expression underscores the need to remove this signal for full functional
      differentiation of this tissue. Our findings support the proposal that the
      mammary gland's normal response to the progesterone-signal is dependent upon
      specific spatial organizational patterns of PR expression and that derailment in
      these cellular processes may contribute to abnormal mammary development,
      including cancer. This review concludes by emphasizing the need to identify the
      downstream molecular targets that mediate progesterone's effects in this tissue.
      Identification of such targets will not only enhance our mechanistic
      understanding of progesterone's role in mammary development and cancer, but may
      also facilitate the formulation of new design strategies in breast cancer
      diagnosis and/or treatment.

PMID- 14667969
TI  - Steroid receptors and proliferation in the human breast.
AB  - Despite recent gains in our knowledge of the hormonal control of proliferation
      and differentiation in the rodent mammary gland, the factors regulating these
      processes in the human are poorly understood. We have developed a model in which
      intact normal human breast tissue is grafted subcutaneously into adult female
      athymic nude mice and treated with oestrogen (E) and/or progesterone (P) at human
      physiological serum levels. We have shown that (i) E and not P is the major
      epithelial cell mitogen in the adult non-pregnant, non-lactating breast, (ii) E
      induces progesterone receptor (PR) expression and (iii) PR expression is
      maximally induced at low E concentrations while a higher amount of E is required
      to stimulate proliferation. These data raised the question of whether one cell
      type demonstrated two different responses to the two different E concentrations
      or whether PR expression and proliferation occurred in separate cell populations.
      Using dual label immunofluorescence, we showed that steroid receptor expression
      and proliferation (Ki67 antigen) are detected in separate cell populations in
      normal human breast epithelium, and that cells expressing the oestrogen receptor
      alpha (ERalpha) invariably contained the PR. We also reported that this
      separation between steroid receptor expression and proliferation observed in the
      normal human epithelium is disrupted at an early stage in breast tumourigenesis.
      One interpretation supported by our recent findings is that some ERalpha/PR
      positive epithelial cells are quiescent breast stem cells that act as "steroid
      hormone sensors". Such hormone sensor cells might secrete positive or negative
      paracrine/juxtacrine factors dependent on the prevailing E or P concentration to
      influence the proliferative activity of adjacent ERalpha/PR-negative epithelial
      cells.

PMID- 14667970
TI  - Progesterone receptors in endometrial cancer invasion and metastasis: development
      of a mouse model.
AB  - Progestagens inhibit growth of endometrial cancer cells in vivo and in vitro, and
      also are reported to inhibit endometrial cancer cell invasion. The progesterone
      receptor (PR) isotypes PRA and PRB have different transcriptional activity. There
      are indications that relative over expression of PRB could lead to development of
      a more invasive phenotype in endometrial cancer. To study the effect of
      progestagens and the two PR isotypes on tumor dissemination, in vitro and in vivo
      models should be applied. The Ishikawa endometrial cancer cell line (clone 3H12)
      was transfected to stably express a high level of human PRB (hPRB), which
      resulted in the PRB-1 sub-cell line. Ovariectomized athymic NMRI nu/nu mice were
      injected intraperitoneally with these PRB-1 cells. After 3, 5 and 10 weeks, the
      animals were sacrificed. Spread of PRB-1 cells in and outside the peritoneal
      cavity was studied macroscopically and microscopically, and also by PCR
      detection. After 10 weeks, the PRB-1 cells had formed extensive tumor mass in the
      peritoneal cavity. Also, cells could be detected outside the peritoneal cavity,
      indicating metastatic ability of these cells. The present study describes an in
      vivo model that can provide a valuable tool in studying the influence of
      progestagens and the two PR isotypes on endometrial cancer cell invasion and
      metastasis.

PMID- 14667971
TI  - Paracrine regulation of endometrial function: interaction between progesterone
      and corticotropin-releasing factor (CRF) and activin A.
AB  - Under the influence of ovarian steroid hormones, endometrial cells aer able to
      produce a wide variety of growth factors and peptide hormones that area believed
      to promote: (1) physiological growth and differentiation during the endometrial
      cycle; (2) decidualization, an essential preparative event for establishment of
      pregnancy; and (3) pathological growth and differentiation in endometriosis and
      cancer. Among the local factors produced by the human endometrium, corticotropin
      releasing factor (CRF) and activin A have been evaluated in terms of localization
      and effects. CRF is a neuropeptide expressed by the epithelial and stromal cells
      of the human endometrium in increasing amounts from the endometrial proliferative
      to the secretory phase. CRF expression also increases in the pregnant
      endometrium, from early in the pregnancy until term. CRF-type 1 receptor mRNA is
      only expressed by stromal cells. Progesterone induces CRF gene expression and
      release from decidualized cells and CRF decidualizes cultured stromal endometrial
      cells. Urocortin, a CRF-related peptide, has been identified in endometrial
      epithelial and stromal cells, and its function is still under investigation.
      Activin A is a growth factor expressed in increasing amounts throughout
      endometrial phases by both epithelial and stromal cells. This growth factor is
      secreted into the uterine cavity with higher levels in the secretory phase.
      Maternal decidua expresses activin A mRNA in increasing amounts from early
      pregnancy until term. Human endometrium also expresses activin-A receptors and
      follistatin, its binding protein. Activin A decidualizes cultured human
      endometrial stromal cells (an effect reversed by follistatin) and modulates
      embryonic trophoblast differentiation and adhesion. Activin A is expressed in
      endometriosis and endometrial adenocarcinoma.

PMID- 14667972
TI  - Two pathways of progesterone action in the human endometrium: implications for
      implantation and contraception.
AB  - The endometrium is the site of implantation and pregnancy. Preparation for this
      important biological event relies primarily on progesterone, which takes the
      estrogen-primed endometrium toward a state of receptivity. As a steroid target
      tissue, the endometrium is also prone to abnormal growth sometimes leading to the
      development of hyperplasia or cancer. It is the balance between estrogen and
      progesterone that maintains the endometrium in a state of health and provides the
      synchronous timing necessary for a successful implantation to occur. In our
      efforts to understand the role of progesterone in the endometrium we have focused
      on the use of specific protein biomarkers. Based on examination of a cell
      adhesion molecule, the alphavbeta3 integrin, and its ligand, osteopontin, we have
      come to conclude that progesterone action can be direct or indirect. Progesterone
      acting on the stromal compartment provides paracrine mediators that influence
      epithelial gene expression. Conversely, acting directly, progesterone may
      primarily stimulate gene expression of the endometrial epithelium. The complexity
      of the system is extended since progesterone itself works through two different
      receptor isoforms. Regulated differential expression of PR-A versus PR-B also
      appears to fine tune the effect of progesterone on specific genes. Progesterone
      may also inhibit specific genes that undergo cyclic variation during the
      menstrual cycle. Together, using in vitro models we have shown that progesterone
      dynamically regulates gene expression in the endometrium and that imbalances
      between estrogen and progesterone may have far reaching consequences on normal
      cycle fecundity and on the balance between health and disease in this hormone
      target tissue.

PMID- 14667973
TI  - Effects of progesterone on growth factor expression in human uterine leiomyoma.
AB  - It is now evident that the use of levonorgestrel-releasing intrauterine system
      (LNg-IUS) is effective for long-term management of menorrhagic women with uterine
      myomas because of a striking reduction in menorrhagia. This prompted us to
      characterize the effects of progesterone (P4) on the growth and apoptosis of
      uterine leiomyoma cells. On the other hand, we have recently noted that epidermal
      growth factor (EGF) and IGF-I play a crucial role in prompting uterine leiomyoma
      growth through stimulating the proliferative potential and inhibiting apoptosis
      of cultured human leiomyoma cells. In the present review, attention was paid to
      evaluate the effects of P4 on the expression of growth factors (EGF, IGF-I) and
      apoptosis-related factors (TNFalpha, Bcl-2 protein) in cultured uterine leiomyoma
      cells. Treatment with P4 augmented EGF and Bcl-2 protein expression, but
      inhibited IGF-I and TNFalpha expression in cultured leiomyoma cells. It is known
      that TNFalpha induces apoptosis in a variety of cell types and Bcl-2 protein is
      an apoptosis-inhibiting gene product. Thus, the results obtained suggest that P4
      has dual actions on uterine leiomyoma growth: one is to stimulate leiomyoma cell
      growth and survival through up-regulating EGF and Bcl-2 protein expression as
      well as down-regulating TNFalpha expression in those cells, and the other is to
      inhibit leiomyoma cell growth through down-regulating IGF-I expression in those
      cells. This may explain why the size of uterine myomas during use of LNg-IUS
      increases in some but decreases in other instances. This may also explain why the
      size of uterine myomas during pregnancy does not increase despite the
      overwhelming increase in circulating concentrations of sex steroid hormones.

PMID- 14667974
TI  - Actions of progesterone and its 5alpha-reduced metabolites on the major proteins
      of the myelin of the peripheral nervous system.
AB  - The sciatic nerve, and the Schwann cells in particular, are able to synthesize
      progesterone and possess the enzymes forming the 5alpha-reduced and the 3alpha
      5alpha-reduced derivatives of progesterone: dihydroprogesterone and
      tetrahydroprogesterone. Moreover, the progesterone receptor (PR) is present in
      the sciatic nerve and in Schwann cell cultures. These facts suggest that
      progesterone and its derivatives might play a role in the control of the
      synthesis of the two major proteins of the peripheral nervous system (PNS): the
      glycoprotein Po (Po) and peripheral myelin protein 22 (PMP22). We have shown
      that: (a) dihydroprogesterone enhances the low mRNA levels of Po in the sciatic
      nerve of aged male rats; (b) progesterone and its derivatives stimulate the gene
      expression of Po in the sciatic nerve of adult rats and in Schwann cell cultures;
      (c) tetrahydroprogesterone increases PMP22 gene expression in the sciatic nerve
      of adult rats and in Schwann cell cultures. In additional experiments, utilizing
      agonists and antagonists of PR and GABAA receptor, we have observed that
      progesterone and its derivatives control Po gene expression via the PR, while
      tetrahydroprogesterone modulates the expression of PMP22 through the GABAA
      receptor.

PMID- 14667975
TI  - In vitro effects of progesterone and progestins on vascular cells.
AB  - The impact of progesterone on the cardiovascular system is relevant, but not as
      well characterized as the effects of estrogens. The recent early interruption of
      the conjugated equine estrogens (CEE)-medroxyprogesterone acetate (MPA) arm of
      the Women's Health Initiative trial, but not of the parallel CEE-only treatment
      arm, suggesting the possibility of harmful cardiovascular effects of the
      progestins, boosts the debate on the role of progesterone and progestins on the
      vascular tree. The data available up to now show the presence of important
      regulatory effects of progestagens on vascular cells. Additionally, the presence
      of a progestagen results in diverse modifications of the effects of estrogens,
      sometimes acting synergically, others being neutral or antagonizing estrogens'
      effects. Notwithstanding the availability of consistent observations on the
      functional effects of progestins on the cardiovascular system, the molecular
      mechanisms of progestins actions on vascular cells have been up to now only
      scarcely characterized. Novel mechanisms of signal transduction are being
      discovered for progesterone receptors in different tissues, some of which are
      independent of gene transcription regulation, and are therefore indicated as
      "nongenomic." Furthermore, the contribution to signal transduction of co
      activators is currently widely investigated, in order to understand the ways to
      tissue-specificity and to engineer new progesterone receptor modulators. The
      understanding of the molecular basis of progesterone receptor signaling in
      vascular tissue is therefore of paramount importance for the development of
      hormonal agents with an optimal cardiovascular profile.

PMID- 14667976
TI  - Endocrine regulation of cervical ripening in humans--potential roles for gonadal
      steroids and insulin-like growth factor-I.
AB  - Cervical softening is crucial for a normal parturition and corresponds to
      remodeling of the dominating cervical extra cellular matrix (ECM). The onset of
      labor as well as cervical ripening is under hormonal control. To get further
      information about the endocrine regulation of term cervical ripening the
      following study was undertaken: cervical biopsies were obtained vaginally at
      elective caesareans, after normal vaginal delivery and after PGE2 or
      antiprogestin RU486. Biopsies from non-pregnant women served as controls. The
      concentrations of estrogen receptor (ER) and progesterone receptor (PR) protein
      were quantitated by EIA and the mRNA levels by solution hybridization. The
      ERalpha and beta were localized by immunohistochemistry, identified by RT-PCR and
      quantitated by solution hybridization. The co-localizations of CD45 (leukocyte
      antigen) and CD68 (macrophage antigen) were studied by immunohistochemistry. The
      cervical concentrations of ER and PR proteins decreased at term to 15 and 25%,
      respectively, compared to the non-pregnant levels. A further decrease was
      measured in the maximal ripened cervix at parturition. The mRNA levels were
      unchanged but IGF-I mRNA reached a maximum at term. ERalpha mRNA was
      significantly decreased until delivery, whereas ERbeta mRNA, like IGF-I; was
      maximum at term. By immunostaining ERbeta could be co-localized with CD45
      leukocyte antigen and CD68 macrophage specific antigen. Oral administration of
      RU486 induced a significant increase in ER protein concentration, whereas PGE2
      and spontaneous ripening did not. These findings indicate that cervical ripening
      is related to significant local hormonal changes.

PMID- 14667977
TI  - Progestin-regulated expression of tissue factor in decidual cells: implications
      in endometrial hemostasis, menstruation and angiogenesis.
AB  - Expression of tissue factor (TF), the primary initiator of hemostasis via
      thrombin formation, is induced during progesterone (P4)-stimulated
      decidualization of human endometrial stromal cells (HESCs), and remains elevated
      in decidualized HESCs of luteal and gestational endometrium. In HESC monolayers,
      progestins elevate TF mRNA and protein levels and estradiol (E2) plus progestin
      further enhance TF levels for weeks despite no response to E2 alone. This in
      vitro model mimics the chronic differential ovarian steroid upregulation of TF
      levels associated with in vivo decidualization. After incubation of HESCs with E2
      plus progestin to elevate TF expression, the antiprogestin RU486 completely
      reversed this upregulation. Thus, progesterone withdrawal transformed
      decidualization-associated hemostasis of the luteal phase endometrium to the
      hemorrhagic milieu of menstruation. Transient transfections with TF promoter
      constructs containing SP and EGR-1 binding sites before and after inactivation by
      site-directed mutagenesis revealed that Sp1 mediates basal and progestin-enhanced
      TF transcriptional activity. Progesterone receptor involvement in TF expression
      was further confirmed since RU486 was a pure antagonist of progestin-enhanced TF
      mRNA and protein expression, and progestin-enhanced, but not basal, Sp1-mediated
      transcriptional activity. Enhanced TF mRNA and protein levels in HESCs require co
      incubation with progestin and epidermal growth factor receptor (EGFR) agonist
      indicating that the EGFR mediates progestin-enhanced TF expression. A peak in the
      primary angiogenic agent, vascular endothelial growth factor (VEGF) in luteal
      phase endometrium may be indirectly regulated by P4. Neither E2, nor progestin,
      nor E2 plus progestin affected VEGF expression in glandular epithelial and
      stromal cells, whereas thrombin enhanced VEGF mRNA and protein levels in
      decidualized HESCs, but not in the epithelial cells. Transudation of clotting
      factors to perivascular decidual cell TF in the luteal phase would generate
      thrombin, enabling it to act as an autocrine enhancer of VEGF in decidualized
      HESCs. Abnormal uterine bleeding complicates long-term progestin only
      contraceptive use. After Norplant administration, endometrial VEGF levels are
      elevated and TF levels are selectively enhanced in decidualized HESCs at bleeding
      sites. Over-expressed VEGF causes blood vessels to become leaky, increasing
      clotting factor access to decidualized HESC-expressed TF to promote feed-forward
      thrombin and VEGF formation. Since thrombin and VEGF induce angiogenesis via
      separate endothelial cell receptors, they may synergize to elicit aberrant
      angiogenesis, and ultimately lead to focal bleeding.

PMID- 14667978
TI  - Steroidogenesis and apoptosis in the mammalian ovary.
AB  - Ovarian cell death is an essential process for the homeostasis of ovarian
      function in human and other mammalian species. It ensures the selection of the
      dominant follicle and the demise of excess follicles. In turn, this process
      minimizes the possibility of multiple embryo development during pregnancy and
      assures the development of few, but healthy embryos. Degeneration of the old
      corpora lutea in each estrous/menstrual cycle by programmed cell death is
      essential to maintain the normal cyclicity of ovarian steroidogenesis. Although
      there are multiple pathways that can determine cell death or survival, crosstalk
      among endocrine, paracrine and autocrine factors, as well as among
      protooncogenes, tumor suppressor genes, survival genes and death genes, plays an
      important role in determining the fate of ovarian somatic and germ cells. The
      establishment of immortalized rat and human steroidogenic granulosa cell lines
      and the investigation of pure populations of primary granulosa cells allows
      systematic studies of the mechanisms that control steroidogenesis and apoptosis
      in granulosa cells. We have discovered that during initial stages of granulosa
      cell apoptosis progesterone production does not decrease. In contrast, we found
      that it is elevated up to 24h following the onset of the apoptotic stimuli
      exerted by starvation, cAMP, p53 or TNF-alpha stimulation, before total cell
      collapse. These observations raise the possibility for an alternative unique
      apoptotic pathway, one not involving mitochondrial Cyt C release associated with
      the destruction of mitochondrial structure and steroidogenic function. Using mRNA
      from apoptotic cells and affymetrix DNA microarray technology we discovered that
      granzyme B, a protease that normally resides in T cytotoxic lymphocytes and
      natural killer cells of the immune system is expressed and activated in granulosa
      cells. Thus, the apoptotic signals could bypass mitochondrial signals for
      apoptosis, which can preserve their steroidogenic activity until complete cell
      destruction. This unique apoptotic pathway assures cyclicity of estradiol and
      progesterone release in the estrous/menstruous cycle even during the initial
      stages of apoptosis.

PMID- 14667979
TI  - The significance of the 20-carbonyl group of progesterone in steroid receptor
      binding: a molecular dynamics and structure-based ligand design study.
AB  - Polar functional groups in the A- and D-ring (positions 3 and 17beta or 20) are
      common to all natural and synthetic steroid hormones. It was assumed that these
      pharmacophoric groups are involved in strong hydrogen bonding interactions with
      the respective steroid receptors. High resolution X-ray structures of the
      estrogen and androgen receptors have confirmed these assumptions. Also site
      directed mutagenesis studies of the human progesterone receptor (hPR) suggest an
      important role for Cys891 in the recognition of the progesterone 20-carbonyl
      group. Surprisingly, the crystal structure of the hPR ligand binding domain (LBD)
      in complex with progesterone suggests that the carbonyl oxygen in position 20
      (O20) is not involved in hydrogen bond contacts. To investigate these surprising
      and contradicting results further, we performed a molecular dynamics simulation
      of the hPR-progesterone complex in an aqueous environment. The simulation
      revealed hPR-Cys891 as the sole but weak hydrogen bonding partner of progesterone
      in the D-ring. In contrast to the site-directed mutagenesis data a major role of
      hPR-Cys891 in progesterone recognition could not be confirmed. Isolated hydrogen
      bond acceptors, such as the prosterone O20 group, in a relatively lipophilic
      environment of the receptor led to a decrease in affinity of the ligand. Based on
      this consideration and the structure of the PR, we designed compounds lacking
      such an acceptor function. If the X-ray structure and the calculations were
      right, these compounds should bind with comparable or higher affinity versus that
      of progesterone. E-17-Halomethylene steroids were synthesized and
      pharmacologically characterized in vitro and in vivo. Although the compounds are
      unable to form hydrogen bonds with the hPR in the D-ring region, they bind with
      superior affinity and exert stronger in vivo progestational effects than
      progesterone itself. Our investigations have confirmed the results of the X-ray
      structure and disproved the old pharmacophore model for progestogenic activity,
      comprising two essential polar functional groups on both ends of the steroid
      core. The 20-carbonyl group of progesterone is likely to play a role beyond PR
      binding, e.g. in the context of other functions via the androgen and
      mineralocorticoid receptors and as a site of metabolic inactivation.

PMID- 14667980
TI  - All progestins are not created equal.
AB  - A variety of progestins are available for therapeutic use. It is convenient to
      classify them into those related in chemical structure to progesterone or
      testosterone. Progestins related to progesterone can be subdivided into pregnanes
      and 19-norpregnanes, whereas those related to testosterone can be subdivided into
      those with and without a 17-ethinyl group. 17-Ethinylated progestins consist of
      the families of norethindrone (estranes) and levonorgestrel (13-ethylgonanes).
      Progestins administered orally undergo extensive hepatic first pass metabolism
      primarily by reduction and conjugation, and in most instances, relatively high
      progestin doses are required for therapeutic use. There are limited reliable data
      on the pharmacokinetics of most progestins. Some progestins are prodrugs,
      requiring transformation prior to exhibiting progestational activity. Qualitative
      and quantitative tests utilizing either human or animal species have been used to
      establish progestin potency. However, profound differences in progestational
      activity are often observed between human and animal tissues. Also, there is a
      misconception about androgenicity of progestins due largely to extrapolation of
      data from rat studies to the human. Progestins differ widely in their chemical
      structures, structure-function relationships, metabolism, pharmacokinetics, and
      potencies; they are not created equal.

PMID- 14667981
TI  - Conception and pharmacodynamic profile of drospirenone.
AB  - Progesterone is more than a progestin. Beyond functions in cycle and pregnancy,
      progesterone binds with high affinity to the mineralocorticoid receptor (MR)
      acting as an antagonist, with obvious significance for electrolyte homeostasis,
      an array of MR-related functions in the circulation as well as in the CNS.
      Progesterone induces natriuresis at physiological concentrations. Lack of
      antimineralocorticoid activity with conventional progestins may account for
      sodium and water retention, minor elevation of blood pressure and "pill
      hypertension" in susceptible women on oral contraceptives. Ethinylestradiol (EE)
      contributes to this problem by distinct activation of the renin-angiotensin
      aldosterone (RAAS) system. Drospirenone (DRSP: 6beta,7beta,15beta,16beta
      dimethylene-3-oxo 17alpha-pregn-4-ene-21,17 carbolactone) is the first synthetic
      progestin with antialdosterone activity. DRSP and progesterone bind to PR in
      uterine (affinity of both is about 30% of R5020) and MR in kidney cytosol
      (affinity about 230 and 100% of aldosterone, respectively). Intrauterine
      administration of DRSP in silastic tubes induced maximum local progestational
      effects in rabbits. At systemic subcutaneous (s.c.) administration (McPhail
      assay) full endometrial transformation was obtained at 1mg per animal per day. At
      1-3mg DRSP per animal per day subcutaneously, pregnancy maintenance after
      ovariectomy, antiovulatory activity, and antimineralocorticoid activity were seen
      in the respective assays in rats. The latter activity indicates about eight-fold
      higher potency than spironolactone. DRSP decreased blood pressure in male
      hypertensive rats, whereas an increase was noted under conventional progestins.
      DRSP also prevented hypertension and fetal growth retardation in pregnant rats
      after L-NAME, an inhibitor of nitric oxide synthase. DRSP has antiandrogenic
      activity. Feminizing effects were recorded during sexual differentiation in male
      fetuses at high doses. Powerful antiandrogenic effects were also seen in gonad
      intact and testosterone substituted castrated male rats. The antiandrogenic
      potency of DRSP is superior to that of spironolactone but below that of
      cyproterone acetate. Endometrial transformation, inhibition of ovulation, and
      antimineralocorticoid, i.e. natriuretic effects and mild antiandrogenic effects
      were recorded at the same range of oral doses (0.5-4 mg per day) in humans.
      Combined with EE (3 mg DRSP+30 microg EE), DRSP provides effective inhibition of
      ovulation and cycle control. Body weight compared to conventional oral
      contraceptives was reduced. DRSP (3 mg per day+15, 20, or 30 microg ethinyl
      estradiol per day) prevented the mild increase of blood pressure seen under a
      conventional levonorgestrel-containing contraceptive and even tended to reduce
      pretreatment blood pressure. Studies on modulation (i.e. inhibition) of
      glucocorticoid effects at the MR in the CNS remain an unexplored and interesting
      area for research.

PMID- 14667982
TI  - Nestorone: clinical applications for contraception and HRT.
AB  - The 19-nor derivatives of progesterone are referred to as "pure" progestational
      molecules as they bind almost exclusively to the progesterone receptor (PR)
      without interfering with receptors of other steroids. In this category is
      Nestorone, which has strong progestational activity and antiovulatory potency
      with no androgenic or estrogenic activity in vivo. These properties make it
      highly suitable for use in contraception and hormonal therapy (HT). Due to its
      high potency, very low doses of Nestorone may be delivered via long-term
      sustained-release delivery systems. Nestorone, 75 or 100 microg per day, released
      by vaginal ring has suppressed ovulation in women, with inhibition of follicular
      maturation. A vaginal ring releasing both 150 microg of Nestorone and 15 microg
      of ethinyl estradiol per day has effectively suppressed ovulation for 13
      consecutive cycles. Nestorone has also been used effectively in a single implant
      for contraception in breastfeeding women and shows promise for use in transdermal
      systems as a contraceptive or for HT when combined with estrogen.

PMID- 14667983
TI  - The preclinical biology of a new potent and selective progestin: trimegestone.
AB  - Trimegestone (TMG) is a 19-norpregnane progestin being developed, in combination
      with an estrogen, for the treatment of postmenopausal symptoms. TMG binds to the
      human progesterone receptor with an affinity greater than medroxyprogesterone
      acetate (MPA), norethindrone (NET), and levonorgestrel (LNG). In contrast, TMG
      binds with low affinity to the androgen, glucocorticoid and mineralocorticoid
      receptor and has no measurable affinity for the estrogen receptor. Compared to
      other progestins, TMG demonstrates an improved separation of its PR affinity from
      its affinity to other classical steroid hormone receptors. In vivo, TMG has
      potent progestin activity. For example, TMG produces glandular differentiation of
      the uterine endometrium in rabbits and is about 30 and 60 times more potent than
      MPA and NET, respectively. In the rat, TMG maintains pregnancy, induces deciduoma
      formation, inhibits ovulation and has uterine anti-estrogenic activity. With
      respect to these endpoints, TMG appears to be more potent and selective on
      uterine epithelial responses than other classical progestin responses. In vivo,
      TMG does not have significant androgenic, glucocorticoid, anti-glucocorticoid or
      mineralocorticoid activity but does have anti-mineralocorticoid activity and
      modest anti-androgenic effects. This overall profile is qualitatively similar to
      progesterone. When TMG is administered chronically, it antagonizes the effect of
      estradiol on the uterus but does not antagonize the beneficial bone sparing
      activity of estradiol. In rat studies evaluating CNS GABAA receptor modulatory
      activity, TMG is less active on this likely undesirable endpoint than
      progesterone and norethindrone acetate, which may translate into fewer mood
      related side effects. The results indicate that TMG is a potent and selective
      progestin with a preclinical profile well suited for hormone replacement therapy.

PMID- 14667984
TI  - Clinical experience with trimegestone as a new progestin in HRT.
AB  - Trimegestone (TMG) is a novel, 19-norpregnane progestin, which demonstrates
      endometrial selectivity with a reduced progestin-related side effect profile when
      compared to several other currently marketed progestins. TMG has been studied in
      combination with 17beta-estradiol (17beta-E2) and conjugated equine estrogens
      (CEE). TMG-containing HRT agents were effective in relieving vasomotor symptoms
      and providing protection from endometrial hyperplasia with < or =1% hyperplasia.
      In clinical trials with sequential regimens, TMG provided predictable withdrawal
      bleeding associated with a low incidence of irregular and prolonged bleeding.
      Clinical studies of continuous combined regimens of estrogen/TMG combinations
      demonstrated high levels of amenorrhea. Both 17beta-E2 and CEE/TMG combinations
      have shown improved bone mineral density and quality-of-life assessments. Both
      continuous combined and sequential regimens of 17beta-E2/TMG and CEE/TMG have a
      favorable clinical profile. TMG provides an important new option for the
      treatment of postmenopausal symptoms and the prevention of osteoporosis.

PMID- 14667985
TI  - Use of dydrogesterone as a progestogen for oral contraception.
AB  - Dydrogesterone is a potent orally active progestogen that has been used in
      clinical practice for over 40 years. Chemically, it belongs to the class of
      retrosteroids. Dydrogesterone is closely related to endogenous progesterone. It
      differs from most other synthetic progestogens in that it has no estrogenic,
      androgenic, glucocorticoid, or anabolic effects. The use of progestogens such as
      dydrogesterone is indicated in all cases of relative or absolute endogenous
      progesterone deficiency. Nowadays, dydrogesterone is mainly used in hormone
      replacement therapy (HRT). The present pilot study explored whether
      dydrogesterone could also be used as a progestogen for oral contraception. Given
      its highly favorable safety and tolerability profile, it would provide
      improvement over existing progestogens currently used in oral contraceptives
      (OCs). The results of this study indicate that dydrogesterone might indeed be a
      suitable candidate for use in oral contraception. This concept is currently being
      investigated further in two open-label phase II trials.

PMID- 14667986
TI  - The progesterone derivative dydrogesterone abrogates murine stress-triggered
      abortion by inducing a Th2 biased local immune response.
AB  - Stress is known to induce abortions in mice and humans, putatively via increased
      levels of abortogenic Th1 cytokines and a decrease of progesterone. Adequate
      levels of progesterone exert an antiabortive response through binding to the
      progesterone-receptor, which induces the release of progesterone-induced blocking
      factor (PIBF) from lymphocytes. PIBF is highly pregnancy-protective by induction
      of a Th2 biased immune activity. The aim of this study was to investigate the
      effect of the progesterone derivative dydrogesterone (6-dehydro
      retroprogesterone) in stress-triggered murine abortion. DBA/2J-mated CBA/J female
      mice were randomized in different groups: two groups were treated with different
      dydrogesterone dosages in a single injection before exposure to sound stress on
      Day 5 of pregnancy, one group was exposed to stress without dydrogesterone
      treatment, the fourth group received no stress and no dydrogesterone. On
      gestation Day 13, a highly elevated abortion rate was detected in stressed mice
      compared to control mice. Stressed animals presented lower levels of progesterone
      and PIBF in plasma and a reduced staining intensity of progesterone receptor at
      the feto-maternal interface. Injection of dydrogesterone abrogated the effect of
      stress on the abortion rate. Further, dydrogesterone increased levels of plasma
      PIBF in stressed mice, but did not affect progesterone levels. Interestingly,
      dydrogesterone dramatically increased the percentage of IL-4 positive decidual
      immune cells in stressed mice. Our data suggest that dydrogesterone abrogates
      stress-triggered abortion by inducing a Th2 biased local immune response.

PMID- 14667987
TI  - MPA and postmenopausal coronary artery atherosclerosis revisited.
AB  - Whether progestins, particularly medroxyprogesterone acetate (MPA), attenuate the
      cardiovascular benefits of postmenopausal estrogen replacement therapy (ERT) has
      been controversial for over a decade. Concerns related first to findings that MPA
      attenuated increases of high density lipoprotein cholesterol (HDLC)
      concentrations of postmenopausal women compared to conjugated equine estrogen
      (CEE) alone. That observation was followed by early cynomolgus monkey studies
      that suggested MPA decreased estrogen's cardiovascular benefits (vascular
      reactivity and coronary artery atherosclerosis inhibition). In a more recent and
      larger trial with cynomolgus monkeys, no differences were seen in the coronary
      artery atherosclerosis protective effect of CEE when MPA was co-administered
      (HRT). The lack of attenuation of ERTs benefits by progestins has also been seen
      in at least three studies of carotid artery intima-media thickness (IMT) of
      postmenopausal women. Additionally, the majority of studies of vascular
      reactivity of postmenopausal women have not found differences when CEE is given
      alone or with MPA. Seven observational studies of cardiovascular outcomes of
      postmenopausal women permit separate consideration of ERT versus HRT use; there
      is no evidence of attenuation of ERTs benefits by progestin use. In conclusion,
      it is evident that the current experimental, clinical, and observational data do
      not provide evidence that progestins attenuate estrogen's cardiovascular
      benefits.

PMID- 14667988
TI  - Risk of breast cancer with progestins: critical assessment of current data.
AB  - Whether progestins protect against the risk of breast cancer or enhance that risk
      has been a major area of controversy over the past several years. Observational
      studies have reported conflicting results and experimental studies examining
      whether progestins exert mitogenic or anti-mitogenic actions on breast tissue
      report divergent results. Based upon a wide range of animal, epidemiologic and
      clinical data, most investigators agree that estrogens contribute to the
      development of breast neoplasms. However, the additional effect of progestins on
      this risk has been the subject of substantial discussion and controversy. A
      variety of experiments have been carried out using human breast cancer cells
      grown in vitro and as xenografts in nude mice. These studies demonstrated both
      mitogenic and anti-mitogenic effects depending upon the precise experimental
      conditions. Two potential reasons for these differences include differential
      metabolism of progestins into inhibitory pregnenes or stimulatory 5-alpha-reduced
      pregnanes or the presence of a protein (GPR 30) which allows the anti-mitogenic
      effects of progestins to be manifest. Based upon the conflicting nature of the
      results in experimental studies, we believe that only data in patients provide
      substantial insight into the actions of progestins on the intact human breast.
      Studies have now demonstrated that cell proliferation and breast density is
      higher during the luteal than during the follicular phase of the menstrual cycle.
      In postmenopausal women, long-term exposure to estrogen plus a progestin results
      in a marked enhancement of proliferation of the terminal duct lobular units as
      well as in breast density. These data, taken together, provide substantial
      evidence that progestins are mitogenic on the human breast when given long term
      to postmenopausal women. To critically evaluate the observational studies
      regarding breast cancer risk from progestins, we developed a set of stringent
      criteria for acceptance of individual studies. Four of the five studies meeting
      these criteria reported a greater risk of breast cancer with combination
      estrogen/progestin regimens than with estrogen alone. More importantly, the first
      randomized, prospective, controlled trial of the risk of breast cancer with an
      estrogen/progestin combination (the Women's Health Initiative Study) has now been
      published. This study reported a 26% increased relative risk of breast cancer
      with the estrogen/progestin combination. Based upon these data, we believe that
      progestins do add to the risk of breast cancer over and above that imparted by
      estrogen alone. The attributable risk during use for 5 years or less is small but
      increases logarithmically during long-term use. The majority of data regarding
      progestins are derived from regimens using MPA. However, we conclude from our
      analysis that the burden of proof regarding progestins has now shifted. One must
      now prove that an estrogen/progestin combination is safe with respect to breast
      cancer rather than having to prove it harmful.

PMID- 14667989
TI  - Use of progestins in male contraception.
AB  - Hormonal male contraception aims at suppression of spermatogenesis to azoospermia
      or at least to severe oligoasthenozoospermia, incompatible with the ability to
      induce a pregnancy. The general principle of this approach is based on
      interference with the endocrine regulation of spermatogenesis, i.e. the
      suppression of gonadotropins. Since both FSH (through the Sertoli cell) and LH
      (through the Leydig cell and testosterone (T)) are required for normal
      spermatogenesis, both gonadotropins need to be suppressed as strongly as
      possible. In East Asian men this can be achieved with T alone (preferably in
      depot preparations such as T undecanoate) but only two-thirds of Caucasian men
      respond with adequate sperm suppression. Therefore, in Caucasian men additional
      substances such as GnRH antagonists or progestins are required to suppress the
      pituitary. Over the past 30 years many combinations of various T preparations
      with different progestins have been tested in clinical trials. Since self
      applicable steroid combinations (e.g. oral levonorgestrel or desogestrel with
      transdermal T) showed low effectiveness, currently injections and implants are
      under clinical development. Long-acting intramuscular T esters (e.g. T
      undecanoate), T pellets or implants (e.g. MENT) are combined with injections of
      DMPA or noresthisterone enanthate or with implants containing levonorgestrel or
      etonogestrel. Acute side-effects of these combinations appear to be minimal and
      tolerable, long-term effects need to be investigated.

PMID- 14667990
TI  - Progestins in hormonal therapy (HT) today, tomorrow and the next day: a
      roundtable discussion.

PMID- 14667991
TI  - Progesterone antagonists and progesterone receptor modulators: an overview.
AB  - Since the original description of the structure of the antiprogestin,
      mifepristone, was published, numerous related compounds have been synthesized
      which may function as progesterone antagonists (PAs) or progesterone receptor
      modulators (PRMs). The latter are mixed agonists-antagonists. Both PAs and PRMs
      have therapeutic applications in female health care. Mifepristone is
      predominantly a PA and displays only minimum agonist activity in certain systems.
      Together with a prostaglandin, mifepristone can terminate pregnancies of less
      than 9 weeks duration, and it may also be used at later gestational ages.
      Mifepristone causes expulsion of the uterine contents following intrauterine
      fetal death. A mifepristone-prostaglandin combination has been shown to be very
      effective treatment in women with menses delay of 11 days or less. Many PAs and
      PRMs display antiproliferative effects in the endometrium. Serum estradiol levels
      however remain in the early to mid-follicular phase range. For this reason, they
      have application in the treatment of endometriosis and myoma without being
      associated with bone loss and hypoestrogenism. PRMs may also find application in
      the treatment of dysfunctional bleeding as well as an adjunct to estrogens in
      hormone replacement therapy in postmenopausal women. Many PAs have contraceptive
      potential by suppressing follicular development and blocking the LH surge. Low
      doses may also be potential contraceptives by retarding endometrial maturation
      without affecting ovulation or inducing bleeding. Mifepristone is an excellent
      agent for use as an emergency "postcoital" contraceptive. PAs may also be useful
      in IVF programs to prevent a premature LH surge and to delay the emergence of the
      implantation window. In addition to their use in women's health care,
      mifepristone and several other PAs are potent antiglucocorticoid agents and may
      be used to treat ACTH-independent Cushing's syndrome. They may also be used in
      the treatment of tumors containing steroid receptors and in other situations
      which require suppression of the ACTH-cortisol axis.

PMID- 14667992
TI  - Regulation of gene expression by PRA-910, a novel progesterone receptor
      modulator, in T47D cells.
AB  - Progestins play an important role in women's health and are used in oral
      contraception, hormone therapy, and treatment of reproductive disorders. The
      effects of progestins upon gene expression in breast epithelium are poorly
      understood. In an attempt to characterize the molecular mechanism of progestin
      action, we used a gene expression profiling approach to examine the action of a
      novel progestin in the T47D cell model, a human breast cancer cell line. PRA-910
      is a novel, nonsteroidal progesterone receptor modulator (PRM) with species
      specific activities identified in a screen for selective PRMs. To understand the
      mechanism of action for PRA-910 in T47D cells, we compared its gene regulation to
      progesterone (P4) and RU486 through Affymetrix U95A GeneChip analysis and TaqMan
      RT-PCR. PRA-910, P4, and RU486 regulated 50, 108, and 16 genes by threefold or
      greater versus vehicle, respectively, with 18 genes having similar regulation for
      P4 and PRA-910. These data confirm and extend previous findings for T47D cells.
      We also obtained time course, concentration-response, cyclohexamide sensitivity,
      and PR-specificity data for two progestin-regulated genes, ATP1A1 and CLDN8. Our
      data demonstrate that PRA-910 has a unique gene regulation profile distinct from
      both P4 and RU486. Further investigation of the underlying mechanism for these
      differences is ongoing.

PMID- 14667993
TI  - Pharmacologic properties of CDB(VA)-2914.
AB  - CDB(VA)-2914 (17alpha-acetoxy-11beta-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9
      diene-3,20-dione) is a synthetic steroid that demonstrates potent progesterone
      antagonist activity in vitro and in vivo. Its binding and antagonist potency with
      respect to the glucocorticoid receptor is significantly reduced compared to that
      of mifepristone, indicating that CDB(VA)-2914 belongs to a new class of
      dissociated progesterone receptor modulators that have reduced antiglucorticoid
      activity. The pharmacological effects of CDB(VA)-2914 have been examined in a
      variety of animal models, the results of which are reviewed in this paper.
      CDB(VA)-2914 inhibits ovulation in rats in a dose-dependent manner upon single
      dose oral administration and exhibits antifertility activity during continuous
      low-dose administration. CDB(VA)-2914 is also effective in animal models of
      postcoital contraception. This paper also presents the results of metabolism
      studies undertaken to link the results of the animal models to potential human
      applications. Because of its unique pharmacological profile, CDB(VA)-2914 is a
      promising candidate for use in contraception as well as treatment of uterine
      fibroids and endometriosis.

PMID- 14667994
TI  - Development of the selective progesterone receptor modulator CDB-2914 for
      clinical indications.
AB  - CDB-2914 (17 alpha-acetoxy-11 beta-[4-N,N-dimethylaminophenyl]-19-norpregna-4,9
      diene-3,20-dione) is a 19-norprogesterone derivative that acts as an antagonist
      in progesterone-responsive tissues. It binds to progesterone receptors A and B
      with high affinity. After oral dosing in humans, CDB-2914 serum levels peak at 60
      90 min. CDB-2914 binds to serum proteins and is cleared slowly. Doses of 1, 10
      and 50 mg exhibit proportional increases in peak serum levels, but serum levels
      from higher doses, 100 and 200 mg, are not dose-dependent, suggesting saturation
      of carrier sites. The biological effects of CDB-2914 vary according to time of
      the menstrual cycle that the drug is given. In the mid-follicular phase, CDB-2914
      (50 mg) inhibits follicular development and delays ovulation and menses. At 100
      mg, in some cases the original follicle ceases development and a new follicle is
      recruited. Endometrial maturation is delayed at all doses tested (10, 50, 100
      mg). Given at mid-luteal phase, there was a dose-dependent effect on menses, with
      higher doses (100-200 mg) resulting in earlier menses. On average, CDB-2914 tends
      to lengthen the menstrual cycle by approximately 1-2 days although the amount of
      delay varies with timing in the menstrual cycle and dose.

PMID- 14667995
TI  - Asoprisnil (J867): a selective progesterone receptor modulator for gynecological
      therapy.
AB  - Asoprisnil is a novel selective steroid receptor modulator that shows unique
      pharmacodynamic effects in animal models and humans. Asoprisnil, its major
      metabolite J912, and structurally related compounds represent a new class of
      progesterone receptor (PR) ligands that exhibit partial agonist and antagonist
      activities in vivo. Asoprisnil demonstrates a high degree of receptor and tissue
      selectivity, with high-binding affinity for PR, moderate affinity for
      glucocorticoid receptor (GR), low affinity for androgen receptor (AR), and no
      binding affinity for estrogen or mineralocorticoid receptors. In the rabbit
      endometrium, both asoprisnil and J912 induce partial agonist and antagonist
      effects. Asoprisnil induces mucification of the guinea pig vagina and has
      pronounced anti-uterotrophic effects in normal and ovariectomized guinea pigs.
      Unlike antiprogestins, asoprisnil shows only marginal labor-inducing activity
      during mid-pregnancy and is completely ineffective in inducing preterm
      parturition in the guinea pig. Asoprisnil exhibits only marginal
      antiglucocorticoid activity in transactivation in vitro assays and animal models.
      In male rats, asoprisnil showed weak androgenic and anti-androgenic properties.
      In toxicological studies in female cynomolgus monkeys, asoprisnil treatment
      abolished menstrual cyclicity and endometrial atrophy. Early clinical studies of
      asoprisnil in normal volunteers demonstrated a dose-dependent suppression of
      menstruation irrespective of the effects on ovulation, with no change in basal
      estrogen concentrations and no antiglucocorticoid effects. Unlike progestins,
      asoprisnil does not induce breakthrough bleeding. With favorable safety and
      tolerability profiles thus far, asoprisnil appears promising as a novel treatment
      of gynecological disorders, such as uterine fibroids and endometriosis.

PMID- 14667996
TI  - A role for the androgen receptor in the endometrial antiproliferative effects of
      progesterone antagonists.
AB  - In women and nonhuman primates, treatment with progesterone antagonists
      suppresses estrogen-dependent mitotic activity in the endometrial glands. This
      antiproliferative effect is paradoxical, because progesterone antagonists do not
      bind to the estrogen receptor (ER). While this phenomenon has been termed a
      "functional noncompetitive antiestrogenic effect," it does not occur in all
      species or in all regions of the primate reproductive tract, so is best referred
      to as an "endometrial antiproliferative effect." Recent studies of ours in both
      women and macaques revealed that the endometrial androgen receptor (AR) was
      increased by progesterone antagonist treatment. Because androgens are known to
      suppress estrogen-dependent endometrial proliferation, we hypothesized that the
      AR was involved in the antiproliferative effects induced by progesterone
      antagonists. In a test of this hypothesis, we administered the antiandrogen,
      flutamide, along with progesterone antagonists to ovariectomized, estrogen
      treated macaques. Flutamide counteracted the suppressive effects of the
      progesterone antagonists on endometrial wet weight, thickness, stromal
      compaction, and mitotic index. Hyaline degeneration of the spiral arteries was
      also blocked by flutamide. These data implicate the AR as a functional component
      of the mechanism through which progesterone antagonists induce endometrial
      antiproliferative effects in the presence of estrogens.

PMID- 14667997
TI  - Chronic low-dose antiprogestin impairs preimplantation embryogenesis, but not
      oocyte nuclear maturation or fertilization in rhesus monkeys.
AB  - Continual administration of low doses of the antiprogestin ZK137316 permits
      ovarian/menstrual cyclicity, but prevents pregnancy in female rhesus monkeys. The
      sites of contraceptive action remain unknown. This study determined whether
      chronic, low-dose antiprogestin exposure during follicular development impairs
      oocyte maturation in vivo, as well as fertilization and preimplantation
      embryogenesis in vitro. Adult, female rhesus monkeys exhibiting normal menstrual
      cycles received vehicle (n=9) or 0.03 mg ZK137316 (n=8)/kg body weight i.m. daily
      for 3 months. Controlled ovarian stimulation with recombinant gonadotropins was
      initiated in the 3rd month. Oocytes collected from preovulatory follicles were
      evaluated for nuclear maturity and inseminated in vitro. Preimplantation
      embryonic development was monitored in vitro. The total number of oocytes and
      percentage collected at each nuclear stage were similar in both groups. More
      (P<0.05) atretic oocytes were recovered following antiprogestin relative to
      vehicle treatment. Fertilization rates and percentages of embryos that progressed
      to the morula stage were similar between groups, but antiprogestin-treated
      females exhibited less (P<0.05) normal cleavage. Embryonic development was
      accelerated by 1 day (P<0.05) from the 16-cell to the morula stage in the
      antiprogestin group relative to vehicle. Despite this, the majority of embryos
      became blastocysts within 6 days in vitro in the antiprogestin group, but fewer
      expanded (P=0.09) and hatched (P<0.05) compared to vehicle. During in vivo
      treatment with chronic, low-dose antiprogestin, oocytes retained their ability to
      resume and complete meiosis as well as fertilize following insemination in vitro.
      However, preimplantation embryogenesis in vitro was impaired, particularly during
      the later stages of blastocyst development. Thus, antiprogestin exposure during
      follicular development altered oocyte functions that are critical for normal
      preimplantation embryogenesis; this may contribute to pregnancy prevention.

PMID- 14667998
TI  - Effects of onapristone on postmenopausal endometrium.
AB  - The progesterone antagonist mifepristone (RU486, Exelgyn) has been shown to exert
      a paradoxical agonist effect on postmenopausal endometrium. We conducted a study
      to investigate the effects of the 'pure' antiprogestin onapristone (ZK 98 299,
      Schering AG) on postmenopausal endometrium. Seventeen postmenopausal subjects (45
      62 years), took 2 mg of oestradiol and either placebo, 1 mg onapristone or 10 mg
      of onapristone, daily for 56 days. An endometrial biopsy was performed during the
      final week of treatment and assessed for histology and immunohistochemistry for
      oestrogen receptors (ER), progesterone (PR), androgen receptors (AR) and the cell
      proliferation marker Ki 67. FSH fell in all 14 subjects who completed the study,
      consistent with the effect of oestradiol treatment. There was a dose-dependent
      additive effect of onapristone on suppression of gonadotrophins. All endometrial
      biopsies showed proliferative endometrium. A similar pattern and intensity of
      immunostaining of ER, PR and Ki 67 was observed in all groups, with positive
      immunoreactivity in both glands and stroma. AR immunostaining was observed in
      both glands and stroma from all subjects, but there was an increase in intensity
      of immunostaining within the glandular epithelium of women receiving 10 mg
      onapristone. The antiprogestin onapristone, in contrast to mifepristone, is not
      agonistic on postmenopausal endometrium and does not exert obvious
      antiproliferative effects. It does however cause a dose dependent suppression of
      FSH and LH release.

PMID- 14667999
TI  - Antiprogestins as a model for progesterone withdrawal.
AB  - The key physiological function of the endometrium is preparation for
      implantation; and in the absence of pregnancy, menstruation and repair. The
      withdrawal of progesterone is the initiating factor for breakdown of the
      endometrium. The modulation of sex steroid expression and function with
      pharmacological agents has provided an invaluable tool for studying the
      functional responses of the endometrium to sex steroids and their withdrawal. By
      administration of the antiprogestin mifepristone, it is possible to mimic
      progesterone withdrawal and study local events in early pregnancy decidua that
      may play a role in the process of early pregnancy failure. Our data indicate that
      antagonism of progesterone action at the receptor level results in an up
      regulation of key local inflammatory mediators, including NF-kappaB, interleukin
      8 (IL-8), monocyte chemotactic peptide-1 (MCP-1), cyclooxygenase 2 (COX-2) and
      others in decidua. Bleeding induced by mifepristone in the mid-luteal phase of
      the cycle is associated with changes in the endometrium similar to those that
      precede spontaneous menstruation including up-regulation of COX-2 and down
      regulation of PGDH. Administration of antagonists of progesterone provide an
      excellent model to study the mechanisms involved in spontaneous and induced
      abortion as well as providing information which may help devise strategies for
      treating breakthrough bleeding associated with hormonal contraception.

PMID- 14668000
TI  - Effects of mifepristone on endometrial receptivity.
AB  - At the development of receptivity the endometrium undergoes specific changes.
      Several factors have been suggested as markers of endometrial receptivity. A
      common feature for most of these factors is that they are directly, or
      indirectly, regulated by progesterone. The effect of various doses and regimens
      of mifepristone on endometrial development and markers of receptivity has been
      studied. Timed endometrial biopsies were assessed by immunhistochemistry, reverse
      transcriptase polymerase chain reaction (RT-PCR) and electron microscopy. In
      addition the contraceptive efficacy of these regimens was investigated.
      Administration of 200 mg of mifepristone immediately post ovulation has a
      pronounced effect on endometrial development and on suggested markers of
      receptivity. This regimen has been shown to be an effective contraceptive method.
      When 10 mg is given pre or post ovulation, only minor effects on the endometrium
      are observed. Our studies show that mifepristone, when administered in low doses
      that do not affect ovulation, significantly affects some of the studied markers
      of endometrial receptivity and reduces pregnancy rates; however, these activities
      are more pronounced with the higher dose, which is more effective. Our findings
      provide insight into the regulation of progesterone receptors of various
      suggested markers of endometrial receptivity and the possibility of using
      mifepristone for endometrial contraception.

PMID- 14668001
TI  - Synergistic effects of antiprogestins and iNOS or aromatase inhibitors on
      establishment and maintenance of pregnancy.
AB  - Progesterone is known to be involved in many steps in female reproduction
      including control of implantation and uterine-cervical function during pregnancy.
      Our studies in rats and guinea pigs indicate that progesterone inhibits uterine
      contractility and cervical softening during pregnancy. Progesterone levels or
      actions decline near the end of pregnancy leading to the onset of labor.
      Treatment with progestin agonists prolongs pregnancy and inhibits cervical
      softening, whereas treatment with antiprogestins (mifepristone or onapristone)
      stimulates uterine contractility, cervical softening and premature delivery. Thus
      the effect of progesterone receptor modulators in the uterus and cervix depend up
      on the degree of intrinsic agonistic/antagonistic activities. Our recent studies
      show that progesterone interacts with nitric oxide (NO) to maintain pregnancy and
      that administration of progesterone antagonists with NO synthase inhibitors act
      synergistically to stimulate labor. In addition our studies show that
      combinations of progesterone antagonists with aromatase inhibitors act
      synergistically to induce labor. Similarly antiprogestins interact with NO
      synthase or aromatase inhibitors to block implantation through action on the
      endometrium. These studies suggest new applications for combined therapies of
      progestin receptor modulators with aromatase inhibitors or agents that modify NO
      production for contraception, stimulation of labor, estrogen-dependent diseases
      and improved outcomes in pregnancy.

PMID- 14668002
TI  - The antiprogestin-dependent GeneSwitch system for regulated gene therapy.
AB  - Antiprogestin-controlled gene regulation systems, initially developed by Bert
      O'Malley and colleagues, are based on the unusual properties of certain truncated
      progesterone receptor ligand-binding domains (PR-LBDdelta19). These modified PR
      LBDs have lost the ability to respond to progestins, but have gained the ability
      to respond to antiprogestins as agonists, rather than as antagonists. When a
      modified PR-LBD is joined to specific DNA-binding and transcription activator
      domains, the resultant chimeric protein functions as an antiprogestin-inducible
      transcription factor for transgenes linked to promoters with specific DNA-binding
      sites. Antiprogestin-inducible gene regulation systems have been used to regulate
      transgene expression in cultured cells, transgenic animals, and for in vivo gene
      transfer studies using viral- or plasmid-based vectors. We have designed a
      plasmid-based, muscle-specific GeneSwitch system that is delivered to skeletal
      muscle by electroporation and provides regulated erythropoietin (EPO) expression
      in mice and rats in a manner that is dependent on orally administered
      mifepristone (MFP). Regulation was effective at low doses of MFP and provided
      regulated biological responses (hematocrit changes) for more than 6 months. This
      plasmid-based, antiprogestin-inducible EPO/GeneSwitch system has the potential to
      be a convenient, long-lasting and effective gene-based therapy for the treatment
      of anemia.

PMID- 14668003
TI  - Mechanisms of action of emergency contraception.
AB  - The use of levonorgestrel (LNG) alone or combined with ethinylestradiol (Yuzpe
      regimen), for hormonal emergency contraception (HEC) has been approved in several
      countries whereas in others it is still under debate or has been rejected under
      the claim that these formulations abort the developmental potential of the
      embryo. The issue is whether they act by preventing fertilization or by impeding
      the successful development of the zygote through and beyond implantation. Until
      now, published work has left this issue largely unresolved, and this paucity of
      knowledge sustains heated controversies in many settings. A single study
      indicates that LNG impairs sperm migration in the genital tract of women in ways
      that could interfere with fertilization. Several studies in women examined the
      effects of HEC on the outcome of the leading follicle, but lack of precision in
      the timing of treatment relative to follicular growth, maturation, or rupture
      confers great variability and inconsistency of results within and between
      studies. Nonetheless, results indicate that ovulatory dysfunction may account for
      the prevention of pregnancy in a large proportion of cases. Studies searching for
      possible alterations of the endometrium at the time implantation would normally
      take place, found minimal changes of doubtful significance. Recent studies in
      animals cast serious doubts that LNG prevents pregnancy by interfering with post
      fertilization events. Failure to prevent expected pregnancies is close to 25% in
      women, and this is likely to be accounted for entirely by treatment given too
      late to prevent fertilization. The exact mode of action of HEC remains
      undetermined.

PMID- 14668004
TI  - Mifepristone: a novel estrogen-free daily contraceptive pill.
AB  - When the first synthetic progesterone antagonist (mifepristone) was synthesized
      over 20 years ago, it was clear that it had a potential as an antifertility
      agent. Research into the use of antiprogestogens for contraception have
      concentrated on three general approaches: (1) inhibition of ovulation, (2)
      inhibition of implantation and (3) disruption of implantation or "menstrual
      induction". The effect of mifepristone on the ovarian and endometrial cycle
      depends on dose, timing and frequency of administration. Doses of 10 mg per day
      or more suppress follicular development and estradiol levels. Ovulatory cycles
      are maintained in the dose of less than 2 mg although there is increased
      variability in cycle length. The endometrium shows some minor asynchronous
      changes, although these are not sufficient to prevent pregnancy. We have chosen
      to investigate daily doses between 2 and 5 mg which inhibit ovulation and
      menstruation in over 90% of cycles while still maintaining follicular development
      and levels of estradiol within the range found during the follicular phase. The
      endometrium shows proliferative or cystic changes lined by a layer of inactive
      glandular epithelium set in densely packed stroma. There is, however, an absence
      of proliferative activity as reflected by a reduced mitotic index and Ki67
      staining. These unusual histological appearances are associated with
      downregulation of PR but a massive upregulation of AR in particularly glandular
      epithelium. The antiproliferative effect of mifepristone is reassuring suggesting
      that the risk of atypical hyperplasia due to the effect of prolonged exposure to
      estrogen unopposed by progesterone is low. In a pilot study, there were no
      pregnancies in 200 months of exposure in 50 women who used this method as their
      sole method of contraception. Daily mifepristone could provide a novel
      contraceptive method which should be devoid of the risks associated with estrogen
      containing combined oral contraceptive (COC), e.g. venous thromboembolism. The
      health benefits of avoiding the morbidity associated with menstruation are
      considerable. Recent surveys suggest that amenorrhoea would be popular with many
      women.

PMID- 14668005
TI  - Levonorgestrel and mifepristone in emergency contraception.
AB  - Research on new technologies by the Special Programme of Research, Development
      and Research Training in Human Reproduction at WHO has led to the development of
      two new methods for emergency contraception, the levonorgestrel regimen and a low
      dose mifepristone regimen. In 4 years, the levonorgestrel regimen has already
      been approved in some 95 countries. We review this research and present combined
      data from our multinational trials and combined estimates of efficacy for
      mifepristone and for levonorgestrel separately. Data were available for 6283
      women in 10 mg mifepristone groups and 4098 women in levonorgestrel groups. One
      of these studies compared the two methods, namely a randomized, double-blind
      trial in which we also investigated a single dose of 1.5 mg of levonorgestrel.
      Both levonorgestrel and mifepristone are effective for emergency contraception
      and prevent a high percentage of pregnancies when used within a few days after
      coitus. Mifepristone is associated with later return of menses compared to
      levonorgestrel.

PMID- 14668006
TI  - Mifepristone for the prevention of breakthrough bleeding in new starters of depo
      medroxyprogesterone acetate.
AB  - Depo-medroxyprogesterone acetate (DMPA) is an effective injectable contraceptive
      with worldwide availability. However, it is associated with a high incidence of
      breakthrough bleeding (BTB) during the first 6 months of use which often leads to
      discontinuation. Mifepristone is a progesterone receptor antagonist that has been
      demonstrated to decrease BTB caused by the levonorgestrel subdermal implant
      (Norplant). The purpose of this study was to determine if mifepristone would
      decrease BTB in new starters of DMPA. Twenty regularly cycling women who were new
      starters of DMPA were randomized to receive 50 mg of mifepristone or placebo
      every 2 weeks for 24 weeks. Percent days of BTB and number of cycles with
      bleeding intervals > or =8 and > or =14 days were evaluated using daily bleeding
      diaries. Ovulation was determined by measuring thrice-weekly urinary metabolites
      of estrogen and progesterone. Endometrial concentrations of ER and PR were
      determined by immunohistochemistry. Mifepristone significantly decreased the
      percent days of BTB and the number of cycles with prolonged bleeding intervals
      when compared to placebo. No subject ovulated in either group. ER immunostaining
      increased and PR immunostaining decreased after mifepristone treatment. In
      conclusion, a 50 mg dose of mifepristone taken every 2 weeks decreases the
      incidence of BTB in new starters of DMPA. This effect may be due to modulation of
      endometrial estrogen and progesterone receptors.

PMID- 14668007
TI  - Common trafficking pathway for variant antigens destined for the surface of the
      Plasmodium falciparum-infected erythrocyte.
AB  - Intraerythrocytic Plasmodium falciparum exports proteins to the cytosol and to
      the plasma membrane of the host cell. We here present data revealing the
      existence of a unique common pathway for the surface bound traffic of the
      clonally variant antigens, repeated-interspersed-antigen (RIFINS) and P.
      falciparum erythrocyte-membrane-protein-1 (PfEMP1). RIFIN- and PfEMP1-specific
      antibodies were found to stain single small vesicles (SSV) that bud off from the
      parasitophorus vacuolar membrane (PMV) at 6-10 h post-invasion. Large multimeric
      vesicle (LMV) assemblies, composed of subunits each of a similar size to that of
      a SSV, appeared as the dominant vesicle type carrying the variant antigens in the
      cytosol as the parasites developed into early trophozoite stages (> or = 16 h
      post-invasion). Later, more than 24 h post-invasion, large spinle-like vesicles
      (LSLV) built up as the LMV approached and accumulated underneath the erythrocyte
      membrane. LMV were found to associate both with the Maurer's cleft antigen Pf332
      and with lipids as seen by fluorescent BODIPY-Ceramide staining. Co-traffic of
      Pf332 with RIFINS and PfEMP1 occurred in sub-compartmentalized LMV, as the
      variant antigens co-localized at the outer rim while Pf332 occupied the core of
      the vesicle complex. Formation of LMV for the trafficking of RIFINS and PfEMP1 is
      a prominent feature of freshly isolated P. falciparum and of in vitro propagated
      K+ as well as K- parasites, seemingly independent of the knob-associated
      histidine-rich protein (KAHRP). In vitro cultured 3D7 clones lack LMV formation
      and traffic the variant antigens in vesicles of a similar size to that of the
      SSV.

PMID- 14668008
TI  - A member of a conserved Plasmodium protein family with membrane-attack
      complex/perforin (MACPF)-like domains localizes to the micronemes of sporozoites.
AB  - Pore-forming proteins are employed by many pathogens to achieve successful host
      colonization. Intracellular pathogens use pore-forming proteins to invade host
      cells, survive within and productively interact with host cells, and finally
      egress from host cells to infect new ones. The malaria-causing parasites of the
      genus Plasmodium evolved a number of life cycle stages that enter and replicate
      in distinct cell types within the mosquito vector and vertebrate host. Despite
      the fact that interaction with host-cell membranes is a central theme in the
      Plasmodium life cycle, little is known about parasite proteins that mediate such
      interactions. We identified a family of five related genes in the genome of the
      rodent malaria parasite Plasmodium yoelii encoding secreted proteins all bearing
      a single membrane-attack complex/perforin (MACPF)-like domain. Each protein is
      highly conserved among Plasmodium species. Gene expression analysis in P. yoelii
      and the human malaria parasite Plasmodium falciparum indicated that the family is
      not expressed in the parasites blood stages. However, one of the genes was
      significantly expressed in P. yoelii sporozoites, the stage transmitted by
      mosquito bite. The protein localized to the micronemes of sporozoites, organelles
      of the secretory invasion apparatus intimately involved in host-cell infection.
      MACPF-like proteins may play important roles in parasite interactions with the
      mosquito vector and transmission to the vertebrate host.

PMID- 14668009
TI  - Chloroquine resistance in Plasmodium chabaudi: are chloroquine-resistance
      transporter (crt) and multi-drug resistance (mdr1) orthologues involved?
AB  - We have identified in the rodent malaria parasite Plasmodium chabaudi orthologues
      of two Plasmodium falciparum genes, pfcrt and pfmdr1 which have been implicated
      as determinants of chloroquine resistance in the latter species. The sequences of
      the P. chabaudi genes, denoted, respectively, pccg10 and pcmdr1, were first
      determined in the chloroquine-sensitive clone AS, and found to be highly similar
      to those of P. falciparum. For pccg10, there was a nucleotide sequence identity
      of 68.6% and amino acid sequence identity of 75.1% within the predicted coding
      region. For pcmdr1, the sequence identities were 75.0% (nucleotide) and 78.1%
      (amino acid). The sequences of the genes were then determined in three P.
      chabaudi clones selected from clone AS which possessed three different levels of
      resistance to chloroquine. The sequences of both genes in all mutants were found
      to be identical to those of the sensitive AS from which they had been derived.
      Polymorphic sites were found in both genes between the AS clones and a
      genetically unrelated sensitive clone AJ. Analysis of genetic crosses between AJ
      and resistant AS clones showed no linkage between inherited parental alleles of
      pccrt and pcmdr1 and drug responses of the cloned progeny. This showed that
      neither of these genes, nor genes closely linked to them, were determinants of
      the chloroquine resistance in the P. chabaudi mutants.

PMID- 14668010
TI  - Trypanosoma cruzi response to the oxidative stress generated by hydrogen
      peroxide.
AB  - As an intracellular parasite, Trypanosoma cruzi is exposed to reactive oxygen
      species. The study of the proteins involved in the hydroperoxide detoxification
      cascade, tryparedoxin peroxidase included, may lead to the development of a more
      specific chemotherapy for Chagas'disease. In this work, the involvement of TcCPX
      in T. cruzi resistance to oxidant-mediated injury was investigated. At low
      concentrations of hydrogen peroxide cell proliferation was stimulated and
      parasites increased their resistance to sub-lethal doses of H2O2 (100 microM) if
      previously treated with a non-toxic concentration of H2O2 (20 microM). Incubation
      of cells with different H2O2 concentrations induced a dose-dependent increase in
      TcCPX levels, as detected by Western blotting analysis. The increase in TcCPX
      levels in the presence of high H2O2 concentrations possibly reflects an initial
      cell attempt to promote detoxification. To further demonstrate TcCPX involvement
      in T. cruzi response to oxidative stress, TcCPX overexpressing cells were
      produced. Compared to pTEX transformed cells, pTEX-TcCPX mutant cells showed a
      higher mRNA level (129%), without a corresponding increase in protein production
      (11%), suggesting that regulation of gene expression occurs at post
      transcriptional levels. Furthermore, parasite treatment with 200 microM H2O2 for
      30 min, led to an increase in mRNA (192%), but not in protein levels (24%).
      Higher mRNA levels correlated to protein levels were observed only after longer
      H2O2 incubation periods (1-2 h), suggesting that protein translation occurs
      accordingly to parasite needs. An increase in glucose-6-phosphate dehydrogenase
      activity was observed in pTEX-TcCPX epimastigotes that could provide cells with
      extra reducing power and a higher growth index.

PMID- 14668011
TI  - Arachidonic acid synthetic pathways of the oyster protozoan parasite, Perkinsus
      marinus: evidence for usage of a delta-8 pathway.
AB  - The meront stage of the oyster protozoan parasite, Perkinsus marinus, is capable
      of synthesizing saturated and unsaturated fatty acids including the essential
      fatty acid, arachidonic acid [20:4(n-6)]. Eukaryotes employ either delta-6 (Delta
      6) or delta-8 (Delta-8) desaturase pathway or both to synthesize arachidonic
      acid. To elucidate the arachidonic acid synthetic pathways in P. marinus, meronts
      were incubated with deuterium-labeled precursors [18:1(n-9)-d6, 18:2(n-6)-d4,
      18:3(n-3)-d4, and 20:3(n-3)-d8]. The lipids were extracted, converted to fatty
      acid methyl esters, and analyzed using gas chromatography/mass spectrometry and
      gas chromatography/flame ionization detection. Deuterium-labeled 18:2(n-6),
      20:2(n-6), 20:3(n-6), and 20:4(n-6) were detected in meront lipids after 1-, 3-,
      5-, and 10-day incubation with 18:1(n-9)-d6. Deuterium-labeled 20:2(n-6), 20:3(n
      6) and 20:4(n-6) were found in lipids from meronts after incubation with 18:2(n
      6)-d4 methyl ester. No labeled 18:3(n-6) was detected in either incubation.
      Apparently, when incubated with 18:1(n-9)-d6, the parasite first desaturated
      18:1(n-9)-d6 to 18:2(n-6)-d6 by Delta-12 desaturase, then to 20:2(n-6)-d6 by
      elongation, and ultimately desaturated to 20:3(n-6)-d6 and 20:4(n-6)-d6 using the
      sequential Delta-8 and Delta-5 desaturation. Similarly, when incubated with
      18:2(n-6)-d4, P. marinus converted the 18:2(n-6)-d4 to 20:2(n-6)-d4 by elongation
      and 20:2(n-6)-d4 to 20:3(n-6)-d4 by Delta-8 desaturase then by Delta-5 desaturase
      to 20:4(n-6)-d4. These results provide evidence that P. marinus employed the
      Delta-8 rather Delta-6 pathway for arachidonic acid synthesis. Additional support
      for the presence of a Delta-8 pathway was the demonstrated ability of the
      parasite to metabolize 18:3(n-3)-d4 to 20:3(n-3)-d4 and 20:4(n-3)-d4, and 20:3(n
      3)-d8 to 20:4(n-3)-d6 and 20:5(n-3)-d6 using the sequential position-specific
      Delta-8 and Delta-5 desaturases.

PMID- 14668012
TI  - The Plasmodium circumsporozoite protein is involved in mosquito salivary gland
      invasion by sporozoites.
AB  - Plasmodium sporozoites develop in oocysts on the midgut wall of the mosquito and
      are released into the hemocoel. Approximately 15-20% of oocyst sporozoites will
      successfully attach to and invade salivary glands, their target organ. We have
      previously shown that the major surface protein of sporozoites, the
      circumsporozoite (CS) protein, binds specifically to salivary glands and not to
      other mosquito organs exposed to circulating hemolymph. In addition, a peptide
      from the N-terminal portion of CS protein inhibits binding of the protein to the
      glands. In this study, we have extended these findings and show that both the
      protein and the peptide can inhibit sporozoite invasion of salivary glands.

PMID- 14668013
TI  - Purification, characterization and kinetic properties of the multifunctional
      thioredoxin-glutathione reductase from Taenia crassiceps metacestode
      (cysticerci).
AB  - The multifunctional enzyme thioredoxin-glutathione reductase (TGR) was purified
      to homogeneity from the soluble fraction of Taenia crassiceps metacestode
      (cysticerci). Specific activities of 17.5 and 4.7 U mg(-1) were obtained with
      Plasmodium falciparum thioredoxin and GSSG, respectively, at pH 7.75. Under the
      same conditions, Km values of 17, 15, and 3 microM were respectively calculated
      for thioredoxin, GSSG and NADPH. The kcat/Km ratio of T. crassiceps TGR for both
      thioredoxin and GSSG falls in the range observed for typical thioredoxin
      reductases and glutathione reductases. Purified enzyme also showed glutaredoxin
      activity, with a specific activity of 19.2 U mg(-1) with hydroxyethyl disulfide
      as substrate. Both thioredoxin and GSSG disulfide reductase activities were fully
      inhibited by nanomolar concentrations of the gold compound auranofin, supporting
      the existence of an essential selenocysteine residue. Relative molecular mass of
      native enzyme was 136,000 +/- 3000, while the corresponding value per subunit,
      obtained under denaturing conditions, was 66,000 +/- 1000. These results suggest
      TGR exists as a dimeric protein. Isoelectric point of the enzyme was at pH 5.2.
      Moderate or high concentrations of GSSG, but neither thioredoxin nor NADPH,
      resulted in a markedly hysteretic kinetic, characterized by a lag time before the
      steady state velocity was reached. The magnitude of the lag time was dependent on
      GSSG and enzyme concentration. Preincubation of the enzyme with micromolar
      concentrations of GSH or DTT abolished the hysteresis, suggesting that a thiol
      disulfide exchange mechanism is involved.

PMID- 14668014
TI  - Inositolphosphoceramide is not a substrate for the first steps in the
      biosynthesis of glycoinositolphospholipids in Trypanosoma cruzi.
AB  - The major free glycoinositolphospholipids and protein-linked
      glycoinositolphospholipids in Trypanosoma cruzi contain ceramide as the lipid
      moiety. Ceramide was not found in mammalian glycosylphosphatidylinositol (GPI)
      anchors. An alkylglycerol, either as a lyso species or acylated has been also
      found in T. cruzi anchors. However, unlike African trypanosomes, no
      diacylglycerol was detected in the GPI-anchors. Using a membrane preparation from
      epimastigotes upon labelling with UDP[3H]GlcNAc we identified [3H]GlcNAcPI as the
      first step of GPI biosynthesis. Both, alkylacylglycerol (major) and
      diacylglycerol are constituents of the lipid. Although inositolphosphoceramide is
      the main inositolphospholipid in epimastigotes, it does not incorporate GlcNAc.
      The de-N-acetylation step afforded [3H]GlcN(alkylacylglycerol)PI and we also
      detected the [3H]GlcN(lysoacyl)PI. A new metabolite, phosphoGlcN(lysoacyl)PI,
      which was formed on long incorporation times, was characterized by chemical and
      enzymatic degradations. Several [3H]-Man labelled GPI precursors were obtained by
      in vitro GDP[3H]-Man labelling in the presence of UDPGlcNAc. All of them were
      sensitive to PI-PLC and to saponification conditions, thus, supporting a
      glycerolipid structure.

PMID- 14668015
TI  - Differential accumulation of mutations localized in particular domains of the
      mucin genes expressed in the vertebrate host stage of Trypanosoma cruzi.
AB  - The surface of Trypanosoma cruzi is covered by mucin-type glycoproteins involved
      in parasite protection, attachment and immunoevasion. The gene family coding for
      the mucins expressed by the parasite in the vertebrate host, named TcMUC, is
      composed of several hundred members and presents high variability. The genes
      encoding mucins expressed in the insect-dwelling parasite stages are part of a
      much more homogeneous family, named TcSMUG. Here, we addressed the organization
      and evolution of physically linked T. cruzi mucin genes by sequencing large
      chromosomal fragments containing these genes. Specific accumulation of mutations
      was restricted to particular domains of TcMUC genes, showing that these regions
      have, or have had, an accelerated evolution rate. Sequence analysis of several
      TcMUC genes allowed for the identification of members sharing features of TcMUC I
      and II, thus evidencing that one group of genes was generated from the other. The
      highly conserved intergenic regions of both TcMUC and TcSMUG families contained
      TG-rich microsatellites that were not present in unrelated genes in the cosmids,
      suggesting a role for homologous recombination in shuffling and/or amplification
      of T. cruzi mucin genes. The comparison of putative homologous TcMUC II genes
      from different strains of T. cruzi showed that their central variable domains are
      conserved. This conservation was always higher at the DNA level suggesting
      positive selection in these particular regions of TcMUC II genes.

PMID- 14668016
TI  - Human serum haptoglobin is toxic to Plasmodium falciparum in vitro.
AB  - Innate immune responses are important in the control of malaria, particularly in
      those who have not yet mounted an effective adaptive response. Here we report
      that the human serum acute phase protein, haptoglobin, is toxic to Plasmodium
      falciparum cultured in vitro. This effect is phenotype dependent and occurs
      during the trophozoite phase of the asexual life cycle. We propose that the
      increased levels of haptoglobin seen in the acute phase response may be
      protective against malaria in humans.

PMID- 14668017
TI  - Drug resistance-associated pfCRT mutations confer decreased Plasmodium falciparum
      digestive vacuolar pH.
AB  - Elucidating the altered physiology of various chloroquine resistant (CQR) strains
      of Plasmodium falciparum is essential for understanding the molecular basis of
      CQR. In this study, we have devised several new methods for analyzing digestive
      vacuolar (DV) pH for individual intraerythrocytic parasites under continuous
      perfusion. These use controlled illumination power and novel data acquisition
      software, and are based on either acridine orange (AO) emission spectra or
      ratiometric 5-(and 6-)carboxy-2',7'-dimethyl-3'-hydroxy-6'-N-ethylaminospiro
      [isobenzofuran-1(3H),9'-(9H)xanthen]-3-one (DM NERF) excitation. Results show
      that DV pH is more acidic for laboratory strains of CQR parasites relative to
      chloroquine sensitive (CQS). Using mutant pfcrt allelic exchange clones not
      previously exposed to chloroquine (CQ), we now show a direct association between
      acid DV pH, CQ resistance and mutation of pfcrt to either South American (7G8) or
      South East Asian (Dd2) CQR-associated alleles. Surprisingly, these alleles confer
      a similar degree of DV acidification. Verapamil (VPL) reversed acid DV pH for the
      Dd2 mutant C3(Dd2) clone, in a surprisingly rapid fashion, but did not reverse
      acid DV pH for the 7G8 mutant C6(7G8) clone. Thus, there is a direct link between
      expression of two major CQR-associated pfcrt alleles and altered parasite DV
      physiology. The data also support models that envision direct but allele-specific
      interaction between PfCRT and VPL.

PMID- 14668019
TI  - Ambient glucose concentration and gene expression in Plasmodium falciparum.

PMID- 14668018
TI  - Characterization and cloning of GP50, a Taenia solium antigen diagnostic for
      cysticercosis.
AB  - GP50, a Taenia solium protein diagnostic for cysticercosis has been cloned,
      sequenced, and characterized. GP50 is one diagnostic component of the lentil
      lectin purified glycoprotein (LLGP) antigens that have been used for antibody
      based diagnosis of cysticercosis in a Western blot assay for nearly 15 years.
      GP50 is a glycosylated and GPI-anchored membrane protein. The native protein
      migrates at 50kDa, but the predicted molecular weight of the mature protein is
      28.9. Antigenically active recombinant GP50 has been expressed in a baculovirus
      expression system. The antigenic activity of both the native and recombinant
      proteins is dependent upon the correct formation of disulfide bonds. GP50,
      purified from cysticerci, has two homologs expressed in the adult worm, TSES33
      and TSES38. Both are diagnostic for taeniasis. In spite of the amino acid
      similarities between GP50 and the TSES proteins, each appears to be a stage
      specific antigen. A preliminary evaluation of recombinant GP50 in a Western blot
      assay showed 100% specificity for cysticercosis and 90% sensitivity for
      cysticercosis positive serum samples reactive with the GP50 component of LLGP.

PMID- 14668020
TI  - Schistosoma mansoni histone acetyltransferase GCN5: linking histone acetylation
      to gene activation.

PMID- 14668021
TI  - Effects of depletion and overexpression of the Trypanosoma brucei ribonuclease L
      inhibitor homologue.

PMID- 14668022
TI  - Services for men at publicly funded family planning agencies, 1998-1999.
AB  - CONTEXT: Men's reproductive health needs are receiving increased attention, but
      most family planning clinic clients are female, and clinics have reported
      barriers to serving men. METHODS: A 1999 survey of publicly funded agencies that
      administer family planning clinics asked several questions about current policies
      and services and the number of men served in 1998. Data on 17 services were
      collected, as well as the proportion of clients who were male and agencies'
      barriers to serving men. RESULTS: The services most commonly offered to men in
      1999 were condom provision and sexually transmitted disease (STD) counseling (95%
      of all agencies), contraceptive counseling (93%), and STD treatment (90%) and
      testing (89%). The proportions offering various male reproductive health services
      were lowest among hospital-based clinics. Eighty-seven percent of agencies served
      some male contraceptive or STD clients in 1998; those that did served a mean of
      255 men and a median of 50. The male client caseload increased between 1995 and
      1998 at 53% of agencies, and four out of five agencies were interested in serving
      more men in the future. The most commonly reported barriers to serving men were
      men's unawareness that services were available (58%) and inadequate agency
      funding (55%). CONCLUSIONS: Although most clients of publicly funded family
      planning agencies are women, a nonnegligible number are men. Additional efforts
      are needed to determine the best way to deliver reproductive health services to
      men.

PMID- 14668023
TI  - The other half of the equation: Serving young men in a young women's reproductive
      health clinic.
AB  - CONTEXT: Efforts to improve reproductive health typically target women. Family
      planning agencies serving high-risk young women may be particularly suited to
      integrating young men in their health promotion efforts. METHODS: In 2001, a
      family planning clinic in San Francisco serving primarily young women opened a
      male clinic as part of a male involvement program that includes education and
      outreach components. Client volume was assessed by reviewing billing data. New
      male clients completed questionnaires on their demographic characteristics,
      sexual and health-seeking behavior, and reason for clinic visit. Before and after
      the male clinic opened, female clients completed questionnaires assessing their
      satisfaction with services and their attitudes on males' being served at the
      clinic. Data were analyzed by using descriptive and chi-square statistics.
      RESULTS: In the first year of the male clinic, the number of adolescent and adult
      male clients served at the facility increased by 192% and 119%, respectively,
      over the previous year. Among 110 males making first visits, 88% came for
      sexually transmitted disease testing or treatment. Three-quarters had learned of
      the clinic by word of mouth--from a sexual partner (37%), friend (29%) or sibling
      (6%)--rather than directly from outreach efforts. The proportion of female
      respondents very or mostly satisfied with their care was similarly high before
      (98%) and after (92%) the male clinic opened. CONCLUSIONS: Increasing capacity
      within the female reproductive health model to serve males is feasible. To reach
      at-risk males, "in-reach" efforts with female clients may be as important as
      targeted outreach efforts.

PMID- 14668024
TI  - Man2Man: a promising approach to addressing the sexual and reproductive health
      needs of young men.

PMID- 14668025
TI  - The Young Men's Clinic: addressing men's reproductive health and
      responsibilities.

PMID- 14668026
TI  - Integrating Chlamydia trachomatis control services for males in female
      reproductive health programs.

PMID- 14668027
TI  - Making males mindful of their sexual and procreative identities: using self
      narratives in field settings.

PMID- 14668028
TI  - Adult idiopathic thrombocytopenic purpura.

PMID- 14668029
TI  - Clopidogrel: interactions with the P2Y12 receptor and clinical relevance.

PMID- 14668030
TI  - Platelet counts and interleukin-6 (IL-6) promoter polymorphism in patients with
      Gaucher disease.
AB  - INTRODUCTION: The purpose of this study was to ascertain whether polymorphism of
      the IL-6 promoter gene affects platelet counts among patients with Gaucher
      disease since it has been shown that in healthy individuals, the CC genotype is
      correlated with lower platelet counts. METHODS: Blood samples from all adult
      patients seen at a referral clinic during a 12 month period were taken for PCR
      analysis for the IL-6 promoter polymorphism. Platelet counts were culled from the
      records on date of presentation and prior to advent of enzyme replacement therapy
      where relevant. RESULTS: Of 138 Ashkenazi Jewish patients, 31 patients had
      platelet counts <60,000/mm<PRE>3</PRE> and 37 patients had normal platelet counts
      (>150,000/mm<PRE>3</PRE>). Of the former group, 4/31 (13%) and of the latter
      group, 3/37 (8%), had the CC genotype. Although all seven patients had relatively
      mild Gaucher disease (only one required therapy), there was no statistically
      significant difference in allele frequency of the IL-6 promoter polymorphism in
      either group relative to healthy Ashkenazi Jews. CONCLUSION: Whether comparing
      patients with Gaucher disease with normal platelet counts or with
      thrombocytopenia to healthy Ashkenazi Jews, there was no difference in frequency
      of the CC state. Thus, the IL-6 promoter polymorphism may not influence Gaucher
      disease to induce lower platelet counts as shown in other normal Caucasians.

PMID- 14668031
TI  - Bone marrow and peripheral blood C-kit ligand concentrations in patients with
      thrombocytosis and thrombocytopenia.
AB  - C-kit ligand (stem cell factor, SCF) is a hematopoietic growth factor with
      diverse effects. It has stimulatory effects on megakaryocytopoiesis acting in
      synergism with interleukin-3 (IL-3), thrombopoietin (TPO) and granulocyte
      macrophage colony stimulating factor (GM-CSF). The relationship between SCF and
      megakaryocytopoiesis, especially the correlations between blood and bone marrow
      SCF levels have been not clearly established in the literature. We therefore,
      investigated peripheral and bone marrow SCF levels in patients with
      thrombocytosis and thrombocytopenia. Subjects were divided into three groups:
      those with (i) thrombocytopenia, (ii) thrombocytosis and (iii) healthy adults as
      controls. When the three groups were compared, the mean peripheral blood SCF
      level of the thrombocytosis group (2149+/-197) was significantly higher than the
      thrombocytopenia (1586+/-178) and normal control groups (1371+/-68; p<0.05) and
      the bone marrow SCF level was higher (2694+/-267) than the thrombocytopenia group
      (1700+/-182; p<0.05). In the correlation analysis, considering all the groups
      together the bone marrow and peripheral blood SCF concentrations were positively
      and significantly correlated (p<0.01; r=0.93). Correlations between platelet
      number and both bone marrow SCF concentration (p<0.01; r=0.51) and peripheral
      blood concentrations (p<0.01; r=0.40) were also shown. Our results indicate that
      SCF is operative in the pathological megakaryopoiesis of clonal origin and
      reactive thrombocytosis both in the local bone marrow microenvironment and the
      peripheral circulating blood. We feel that further studies on the platelet-SCF
      relationship and SCF levels in different disease states are required.

PMID- 14668032
TI  - Leukemia associated clonal expansion of TCR Vbeta subfamily T cells.
AB  - The analysis of the T cell receptor (TCR) Vbeta repertoire is one of the most
      sensitive methods to identify the clonal expansion T cells which respond to tumor
      associated antigens. Recently, studies have focused on clonally expanded T cells
      from patients or normal donors induced by leukemia associated antigens in vivo or
      in vitro. Understanding such clonality and restricted usage of TCR Vbeta
      repertoire of leukemia-associated expanded T cells may be useful for the design
      of new immuno-therapeutic strategy for leukemia.

PMID- 14668033
TI  - Urokinase plasminogen activator receptor and soluble matrix metalloproteinase-9
      in acute myeloid leukemia patients: a possible relation to disease invasion.
AB  - Extracellular proteolytic enzymes of the urokinase-type plasminogen activator
      (uPA) and metalloproteinase (MMP) family play a crucial role in the matrix
      degradation and tissue remodeling process characteristic of malignant disorders.
      The receptor for urokinase plasminogen activator (uPAR) serves to localize and
      intensify the action of UPA and is expressed on the surface of malignant cells.
      Although the biological significance of MMP-9 and soluble urokinase receptor in
      growth and progression of lymphoid neoplasm is understood, its clinical
      significance in acute myeloid leukemia (AML) has not been fully elucidated. In
      this study, we determined the levels of soluble urokinase-type plasminogen
      activator receptor (suPAR), cellular uPAR and sMMP-9 in 43 newly diagnosed AML
      patients at diagnosis, before chemotherapy, and also studied 10 normal subjects
      served as a control group. After chemotherapy suPAR and MMP-9 were determined at
      remission and relapse. The levels of suPAR, cellular PAR were significantly
      higher (P= 0.001, 0.001) and MMP-9 was significantly lower (P=0.001) in AML
      patients at diagnosis as compared to controls. suPAR and MMP-9 levels were
      significantly lower in AML patients who achieved complete remission (CR) as
      compared to those who did not (P= 0.001 for both). Levels of suPAR and MMP-9 were
      significantly correlated to peripheral blood blast cells (r= 0.88, P= 0.001; r=
      0.65, P= 0.001, respectively) and blast cell distribution ratio (BCDR, r= 0.84,
      P= 0.001; r=65, P= 0.001, respectively). suPAR, cellular PAR and MMP-9 were
      significantly higher in patients with extramedullary infiltration as compared
      with those without (P= 0.001, 0.001, <0.05). The suPAR, cellular uPAR, and MMP-9
      levels were uneven in AML FAB subtypes being highest in M5(P<0.05 for all). MMP-9
      and suPAR levels were correlated with the disease status. In AML survivors, MMP
      9, cellular uPAR and suPAR were significantly lower as compared to non-survivors
      (P= 0.001 for all). In conclusion, MMP-9 and su PAR levels might be used as a
      marker for disease activity and may contribute to blast cell dissemination. MMP-9
      and suPAR may be target molecules in the strategy of treatment of AML.

PMID- 14668034
TI  - Lamivudine therapy in acute leukemia patients who are hepatitis B surface antigen
      carriers.
AB  - BACKGROUND: Reactivation of hepatitis B in patients receiving chemotherapy for
      acute leukemia may give rise to a variety of clinical patterns including
      hepatitis, asymtomatic hepatic dysfunction, massive hepatic necrosis and fatal
      hepatic failure. Lamivudine is a nucleoside analogue which can directly suppress
      Hepatitis B virus (HBV) replication. We reviewed our combined experience to
      evaluate the role of lamivudine as prophylaxis in acute leukemia patients who
      were HBsAg carriers treated with chemotherapy between July 2000 and October 2002
      at the Numune Education and Research Hospitals (Ankara, Turkey) retrospectively.
      METHODS: We investigated 75 acute leukemia patients who received chemotherapy.
      Thirteen (17.3%) of 75 acute leukemia patients were HbsAg positive and of 7
      (53.3%) were HBV DNA positive. Two patients (patients 5 and 6) had a chemotherapy
      regimen that included corticosteroids and were HBsAg and HBV DNA negative but
      anti HBc total positive. HBsAg positive patients with or without HBV DNA
      positivity were treated with a dose of 100 mg/day lamivudine commencing when
      chemotherapy was initiated. Lamivudine started at the beginning of chemotherapy
      and was maintained for 6 months following the cessation of chemotherapy. During
      lamivudine treatment, Aspartate aminotransferase (AST), Alanine aminotransferase
      (ALT), Gama glutamile transpeptidase (GGT), Alkaline phosphatase (ALP) were
      followed. RESULTS: Of the 8 patients who presented with hepatic dysfunction
      during the first chemotherapy cycle, 4 improved during the second course. After
      completing chemotherapy, the levels of hepatic enzymes were in the normal range
      in all but one patient. With lamivudune prophylaxis, HBV DNA positivity did not
      develop in any of the HBV DNA negative patients. The two patients who received
      corticosteroids with their first chemotherapy cycle became positive for HBsAg and
      HBV DNA and were given Lamivudine when the seroconversion was established. Median
      follow up from the diagnosis of leukemia was 14.5 months. Survival rate at the
      end of follow up was 5 (38%) for the 13 patients. CONCLUSIONS: As this infection
      is endemic in our country and the exposure to blood products is high in these
      patients, HBV infection is more common. Prophylaxis with daily administration of
      lamivudine to HBsAg carriers who are candidates for chemotherapy seems to be
      effective and may prevent chemotherapy induced HBV reactivation and hepatic
      failure.

PMID- 14668035
TI  - Preparative therapies used for those with Fanconi's anemia undergoing stem cell
      transplants and subsequent engraftment rates.
AB  - Fanconi anemia patients are often treated with stem cell transplants to prevent
      myelodysplastic changes or leukemic progression. A variety of preparative
      regimens have been utilized. A case of a 13-year-old child with Fanconi's anemia
      is presented to highlight the preparative therapy utilized, engraftment rates
      which have been seen and the incidence of graft-vs.-host disease (GvHD). A review
      of the literature suggests the most successful preparative therapies with the
      highest engraftment rates and also suggests the best GvHD regimens.

PMID- 14668036
TI  - The use of positron emission tomography with [18F] 2-fluoro-D-2-deoxyglucose (FDG
      PET) in Hodgkin and non-Hodgkin's lymphoma.
AB  - Positron emission tomography (PET) has obtained a place in the management of
      patients with hematologic disease particularly those with lymphoproliferative
      disorders. In the staging and monitoring of cancer, the use of PET in combination
      with fluorine-18 fluorodeoxyglucose (FDG) has already demonstrated its benefit
      when compared with conventional imaging modalities. One such area which has
      already profited from the use of PET is Hodgkin's disease (HD) and non-Hodgkin's
      lymphoma (NHL). Computed tomography and magnetic resonance imaging are equivalent
      in staging and monitoring disease, while gallium-67 imaging is more useful in HD
      and high grade NHL for studies of response to therapy.Paul et al. in 1987 were
      the first to describe PET imaging in patients with lymphoma; since this time a
      number of studies have demonstrated that PET technique is superior to 67 Ga
      imaging in staging lymphoma before therapy and is useful in the evaluation and
      the prediction of relapse after high dose therapy with stem cell
      transplantation.PET is based on the utilisation of positron emitting
      radiopharmaceuticals and the detection in coincidence of the two nearly collinear
      511-keV photons emitted following positron annihilation with an electron in vivo.
      By surrounding the patients with detectors, a large number of acquired coincident
      events can lead to the construction of an image of the in vivo radioisotope
      distribution.

PMID- 14668037
TI  - The regulatory mechanism of IL-6-dependent proliferation of human myeloma cells.
AB  - Multiple myeloma (MM) is a malignant tumor of plasma cells in the bone marrow.
      Interleukin 6 (IL-6) is an indispensable growth factor for myeloma cells. The
      heterogeneity of myeloma cells are the characteristics of MM, categorized into
      five sub-populations, two immature cells, MPC-1<PRE>-</PRE> CD49e<PRE>-</PRE>
      CD45<PRE>+/-</PRE>, intermediate cells, MPC-1<PRE>+</PRE> CD49e<PRE>-</PRE>
      CD45<PRE>+/-</PRE>, and mature cells, MPC-1<PRE>+</PRE> CD49e<PRE>+</PRE>
      CD45<PRE>+</PRE>. Only MPC-1<PRE>-</PRE> CD49e<PRE>-</PRE> CD45<PRE>+</PRE>
      immature cells (~2% of total myeloma cells) respond to IL-6 to proliferate. CD45
      protein tyrosine phosphatase is the determinant of IL-6 dependent cell growth of
      myeloma cells, although well studied IL-6 signal transducing factors, such as, IL
      6Ra, gp130, Jak2, STAT3, and MAPK, are activated and involved in the process.
      Immature CD45<PRE>-</PRE> cells converted to CD45<PRE>+</PRE> cells after IL-6
      stimulation both in U266 cells and sorted myeloma cells from the bone marrow
      aspirates of MM patients. CD45<PRE>-</PRE> cells are relatively resistant to
      serum starvation compared to CD45<PRE>+</PRE> cells. Because IL-6 level in the
      bone marrow is low even in MM patients, the CD45<PRE>-</PRE> phenotype of myeloma
      cells may protect the cells from apoptosis. These findings of a tuning effect of
      CD45 on myeloma cell proliferation may aid the study of IL-6 dependent
      proliferation of myeloma cells and lead to the development of new therapies for
      MM patients.

PMID- 14668038
TI  - Persistent questions about the treatment of severe aplastic anemia in children as
      illustrated by five cases.
AB  - We present our recent experience treating five children with severe aplastic
      anemia (SAA). One patient was transplanted and the remaining 4 patients were
      treated with immunosuppression of various types and duration. These five cases
      illustrate the many outstanding points which remain to be clarified regarding the
      care of children with SAA. We have outlined the treatment options available to
      each of these patients and the path that we followed along with their outcomes.
      Additional research and consideration is necessary to arrive at definitive
      answers to the questions posed by these five cases.

PMID- 14668039
TI  - Arterialization of venous blood for differentiation of sickle cell subjects in
      vaso-occlusive crisis.
AB  - These studies were designed as two experiments. Experiment 1 was performed to
      validate the hypothesis that oxygen saturation of the venous blood may be a
      marker for vaso-occlusive crisis (VOC) in sickle cell patients undergoing
      hydroxyurea (HU) treatments. Experiment 2 was performed to test the hypothesis
      that an acute increase in the blood nitric oxide (NO) concentration by
      administering HU modulates the perception of pain in sickle cell subjects in VOC.
      The percent saturations of oxyhemoglobin (%O<PRE>2</PRE>Hb), reduced hemoblogin
      (%RHb), carboxy-hemoglobin (%COHb), met-hemoglobin (%MHb), fetal hemoglobin
      (HbF), and nitric oxide metabolites were measured in venous blood samples
      collected from sickle cell disease (SCD) who were on and off HU and O<PRE>2</PRE>
      at steady state and during VOC. The results showed the ratio of
      %O<PRE>2</PRE>Hb/RHb in VOC+HU was significantly higher than patients in the
      steady state who were on and off of HU (p<0.05). The %COHb was higher in all SCD
      groups, %COHb values were significantly different in SCD at steady state who were
      on HU. HU and O<PRE>2</PRE> treatment did not play important role on venous blood
      %O<PRE>2</PRE>Hb and pain scores in SCD during VOC. A single oral dose of HU was
      associated with a significant increase in the venous concentration of nitric
      oxide metabolites (NOx), p<0.05. These findings suggest that the ratio
      %O<PRE>2</PRE>Hb/RHb in venous blood and pain scores differentiate HU-untreated
      and HU-treated at steady state subjects from HU-treated subjects in VOC; however,
      the acute increase in venous NOx produced by administering HU to HU-treated
      subjects in VOC does not explain this difference.

PMID- 14668040
TI  - Phlebotomy-mobilized iron as a surrogate for liver iron content in
      hemochromatosis patients.
AB  - We sought to establish the relationship of quantitative hepatic iron measurements
      and phlebotomy-mobilized iron in a large sample of HFE C282Y homozygotes with a
      hemochromatosis phenotype. Thus, we analyzed data from 79 unrelated C282Y
      homozygotes from treatment centers in Rochester, NY and Birmingham, AL who had
      undergone liver biopsy with measurement of hepatic iron content and who had
      achieved iron depletion (serum ferritin <25 ng/l) with quantitative phlebotomy.
      The sample consisted of 57 men and 22 women; their median age at diagnosis was 47
      years (range 23-76 years). Sixty-three of 79 (79.7%) had hepatic iron index (HII;
      MUmol/g dry weight of liver divided by age in years) >=1.9, a conventional
      phenotypic definition of hemochromatosis. The mean quantity of phlebotomy
      mobilized iron (+/- 1 sd) was 6.4 g (+/-4.0 g) in men (range 2.0-18.0 g) and 6.2
      g (+/-5.8) in women (range 0.7-22.5 g). There was a significant positive
      correlation of liver iron levels with phlebotomy-mobilized iron in this patient
      sample (Pearson coefficient 0.75; R<PRE>2</PRE>=55.5%). This relationship was
      also demonstrable when data from males and females were analyzed separately. We
      calculated a phlebotomy-mobilized iron index (MII: phlebotomy-mobilized iron in
      mg divided by age in years) using the corresponding regression equations and
      evaluated its use as a surrogate for HII. Thus, a phlebotomy-mobilized iron of
      3.5 g corresponds to liver iron levels of 80 MUmol/g dry weight, and a MII of 80
      corresponds to HII of 1.9. Forty-six of 79 subjects met all four phenotypic
      criteria for hemochromatosis (liver iron levels >=80 MUmol/g, HII>=1.9,
      phlebotomy-mobilized iron >=3.5 g and MII>=80). Of the 20 subjects with MII<80, 9
      had a HII>=1.9. Conversely, 5 of 16 subjects with HII<1.9 had MII>=80 and 8 had
      phlebotomy-mobilized iron >=3.5 g. Most patients with a hemochromatosis phenotype
      and evidence of moderate or severe iron overload (>80%) are homozygous for the
      common HFE missense mutation C282Y. Thus, clinicians rely increasingly on HFE
      mutation analysis to diagnose hemochromatosis and on quantitative phlebotomy to
      estimate the severity of iron overload in many cases. Liver biopsy is now
      employed in selected patients to visualize fibrosis or cirrhosis and to identify
      coincidental hepatic disease. We conclude that the use of the MII permits a
      retrospective estimation of the age-adjusted severity of iron overload that has a
      diagnostic value similar to that of the HII in hemochromatosis patients with
      C282Y homozygosity.

PMID- 14668041
TI  - Splenic mass in a 42-year-old woman.

PMID- 14668044
TI  - The insulin-like growth factor system.
AB  - The insulin-like growth factor (IGF) system in ubiquitous and plays a role in
      every tissue of the body. It is comprised of ligands, receptors and binding
      proteins, each with specific functions. While it plays an essential role in
      embryonic and post-natal development, the IGF system is also important in normal
      adult physiology. There are now numerous examples of diseases such as diabetes,
      cancer, and malnutrition in which the IGF system is a major player and, not
      surprisingly, there are attempts to affect these disorders by manipulating the
      system.

PMID- 14668045
TI  - The role of the insulin-like growth factors and their binding proteins in glucose
      homeostasis.
AB  - The insulin like growth factors (IGF-I and -II) are structurally and functionally
      related to insulin. While insulin is a key regulator of glucose homeostasis over
      the short term, emerging evidence suggests that the IGFs are involved in the
      longer term glucose homeostasis, possibly by modulating insulin sensitivity.
      Unlike insulin, the IGFs are present in most biological fluids as complexes with
      high affinity binding proteins, the insulin-like growth factor binding proteins
      (IGFBPs). The IGFBPs regulate the bioavailability of the IGFs. Of the six IGFBPs
      identified there is evidence from studies in transgenic mice that both IGFBP-1
      and IGFBP-3 may have a role in glucose regulation.

PMID- 14668046
TI  - Trophic factors and cytokines in early diabetic glomerulopathy.
AB  - The intent of this review is to focus on recent advances in the understanding of
      the factors responsible for the progressive pathologic features of diabetic
      kidney disease, with special attention to various growth factors and cytokines
      that appear to be important in this process. In addition, emphasis is centered on
      relatively early stages of the disease, because animal models have been most
      helpful to date in understanding this stage of the disease process. Although
      tubulointerstitial changes are of critical importance in the progression of
      diabetic nephropathy, especially in the evolution to end-stage renal disease,
      there is a general consensus that glomerular pathology occurs first. Therefore,
      attention is limited to factors that may be important in the development of early
      diabetic glomerulopathy, including transforming growth factor-beta (TGF-beta),
      insulin-like growth factor (IGF)-I, vascular endothelial growth factor (VEGF)-A,
      and connective tissue growth factor (CTGF).

PMID- 14668047
TI  - The insulin-like growth factor system and neurological complications in diabetes.
AB  - The IGF system plays vital roles in neuronal development, metabolism,
      regeneration and survival. It consists of IGF-I, IGF-II, insulin, IGF-I-receptor,
      and those of IGF-II and insulin as well as IGF-binding proteins. In the last
      decades it has become clear that perturbations of the IGF system play important
      roles in the pathogenesis of diabetic neurological complications. In the
      peripheral nervous system IGF-I, insulin, and C-peptide particularly in type 1
      diabetes participate in the development of axonal degenerative changes and
      contributes to impaired regenerative capacities. These abnormalities of the IGF
      system appear to be less pronounced in type 2 diabetes, which may in part account
      for the relatively milder neurological complications in this type of diabetes.
      The members of the IGF system also provide anti-apoptotic effects on both
      peripheral and central nervous system neurons. Furthermore, both insulin and C
      peptide and probably IGF-I possess gene regulatory capacities on myelin
      constituents and axonal cytoskeletal proteins. Therefore, replenishment of
      various members of the IGF system provides a reasonable rational for prevention
      and treatment of diabetic neurological complications.

PMID- 14668048
TI  - Insulin-like growth factor replacement therapy for diabetic neuropathy:
      experimental basis.

PMID- 14668049
TI  - Nerve growth factor and diabetic neuropathy.
AB  - Neuropathy is one of the most debilitating complications of both type 1 and type
      2 diabetes, with estimates of prevalence between 50-90% depending on the means of
      detection. Diabetic neuropathies are heterogeneous and there is variable
      involvement of large myelinated fibers and small, thinly myelinated fibers. Many
      of the neuronal abnormalities in diabetes can be duplicated by experimental
      depletion of specific neurotrophic factors, their receptors or their binding
      proteins. In experimental models of diabetes there is a reduction in the
      availability of these growth factors, which may be a consequence of metabolic
      abnormalities, or may be independent of glycemic control. These neurotrophic
      factors are required for the maintenance of the neurons, the ability to resist
      apoptosis and regenerative capacity. The best studied of the neurotrophic factors
      is nerve growth factor (NGF) and the related members of the neurotrophin family
      of peptides. There is increasing evidence that there is a deficiency of NGF in
      diabetes, as well as the dependent neuropeptides substance P (SP) and calcitonin
      gene-related peptide (CGRP) that may also contribute to the clinical symptoms
      resulting from small fiber dysfunction. Similarly, NT3 appears to be important
      for large fiber and IGFs for autonomic neuropathy. Whether the observed growth
      factor deficiencies are due to decreased synthesis, or functional, e.g. an
      inability to bind to their receptor, and/or abnormalities in nerve transport and
      processing, remains to be established. Although early studies in humans on the
      role of neurotrophic factors as a therapy for diabetic neuropathy have been
      unsuccessful, newer agents and the possibilities uncovered by further studies
      should fuel clinical trials for several generations. It seems reasonable to
      anticipate that neurotrophic factor therapy, specifically targeted at different
      nerve fiber populations, might enter the therapeutic armamentarium.

PMID- 14668050
TI  - Growth factors in proliferative diabetic retinopathy.
AB  - Many growth factors are implicated in the pathogenesis of proliferative diabetic
      retinopathy. Alteration of growth factors and their receptors in diabetes has
      been shown in both experimental and clinical studies. Sustained hyperglycemia
      resulting from long-standing diabetes leads to several biochemical abnormalities
      that consequently result in retinal hypoxia. Retinal oxygenation state regulates
      various growth factors that promote angiogenesis in order to meet the oxygen
      demands of the tissue. However, unregulated expression of these growth factors
      and induction of complex cascades leading to augmentation of other proangiogenic
      factors, which may not be regulated by tissue oxygenation, leads to uncontrolled
      retinal neovascularization and blindness in diabetic patients.

PMID- 14668051
TI  - Role of neuropoietic cytokines in development and progression of diabetic
      polyneuropathy: from glucose metabolism to neurodegeneration.
AB  - Diabetic neuropathy develops as a result of hyperglycemia-induced local metabolic
      and microvascular changes in both type I and type II diabetes mellitus. Diabetic
      neuropathy shows slower impulse conduction, axonal degeneration, and impaired
      regeneration. Diabetic neuropathy affects peripheral, central, and visceral
      sensorimotor and motor nerves, causing improper locomotor and visceral organ
      dysfunctions. The pathogenesis of diabetic neuropathy is complex and involves
      multiple pathways. Lack of success in preventing neuropathy, even with successful
      treatment of hyperglycemia, suggests the presence of early mediators between
      hyperglycemia-induced metabolic and enzymatic changes and functional and
      structural properties of Schwann cells (SCs) and axons. It is feasible that once
      activated, such mediators can act independently of the initial metabolic stimulus
      to modulate SC-axonal communication. Neuropoietic cytokines, including
      interleukin-1 (IL-1), interleukin-6 (IL-6), leukemia inhibitory factor (LIF),
      ciliary neurotrophic factor (CNTF), tumor necrosis factor alpha (TNF-alpha), and
      transforming growth factor beta (TGF-beta), exhibit pleiotrophic effects on
      homeostasis of glia and neurons in central, peripheral, and autonomic nervous
      system. These cytokines are produced locally by resident and infiltrating
      macrophages, lymphocytes, mast cells, SCs, fibroblasts, and sensory neurons.
      Metabolic changes induced by hyperglycemia lead to dysregulation of cytokine
      control. Moreover, their regulatory roles in nerve degeneration and regeneration
      may potentially be utilized for the prevention and/or therapy of diabetic
      neuropathy.

PMID- 14668052
TI  - Toxicogenomics of non-viral vectors for gene therapy: a microarray study of
      lipofectin- and oligofectamine-induced gene expression changes in human
      epithelial cells.
AB  - Of the non-viral vectors, cationic lipid (CL) formulations are the most widely
      studied for the delivery of genes, antisense oligonucleotides and gene silencing
      nucleic acids such as small interfering RNAs. However, little is known about the
      impact of these delivery systems on global gene expression in target cells. In an
      attempt to study the geno-compatibility of CL formulations in target cells, we
      have used microarrays to examine the effect of Lipofectin and Oligofectamine on
      the gene expression profiles of human A431 epithelial cells. Using the
      manufacturer's recommended CL concentrations routinely used for gene delivery,
      cDNA microarray expression profiling revealed marked changes in the expression of
      several genes for both Lipofectin- and Oligofectamine-treated cells. Data from
      the 200 spot arrays housing 160 different genes indicated that Lipofectin or
      Oligofectamine treatment of A431 cells resulted in more than 2-fold altered
      expression of 10 and 27 genes, respectively. The downstream functional
      consequences of CL-induced gene expression alterations led to an increased
      tendency of cells to enter early apoptosis as assessed by annexin V-FITC flow
      cytometry analyses. This effect was greater for Oligofectamine than Lipofectin.
      Observed gene expression changes were not sufficient to induce any significant
      DNA damage as assessed by single cell gel electrophoresis (COMET) assay. These
      data highlight the fact that inadvertent gene expression changes can be induced
      by the delivery formulation alone and that these may, ultimately, have important
      safety implications for the use of these non-viral vectors in gene-based
      therapies. Also, the induced non-target gene changes should be taken into
      consideration in gene therapy or gene silencing experiments using CL formulations
      where they may potentially mask or interfere with the desired genotype and/or
      phenotype end-points.

PMID- 14668053
TI  - Hydroxocobalamin uptake into the cerebrospinal fluid after nasal and intravenous
      delivery in rats and humans.
AB  - The possibility of direct transport of hydroxocobalamin from the nasal cavity
      into the cerebrospinal fluid (CSF) after nasal administration in rats was
      investigated and the results were compared with a human study. Hydroxocobalamin
      was given to rats (n=8) both intranasally (214 microg/rat) and intravenously
      (49.5 microg/rat) into the jugular vein using a Vascular Access Port (VAP). Prior
      to and after drug administration, blood and CSF samples were taken and analysed
      by radioimmunoassay. The AUCCSF/AUCplasma ratio after nasal delivery does not
      differ from the ratio after intravenous infusion, indicating that
      hydroxocobalamin enters the CSF via the blood circulation across the blood-brain
      barrier (BBB). This same transport route is confirmed by the cumulative AUC-time
      profiles in CSF and plasma, demonstrating a 30 min delay between plasma
      absorption and CSF uptake of hydroxocobalamin in rats and in a comparative human
      study. The present results in rats show that there is no additional uptake of
      hydroxocobalamin in the CSF after nasal delivery compared to intravenous
      administration, which is in accordance with the results found in humans. This
      indicates a predictive value of the used rat model for the human situation when
      studying the nose to CSF transport of drugs.

PMID- 14668054
TI  - A multi-domain protein system based on the HC fragment of tetanus toxin for
      targeting DNA to neuronal cells.
AB  - One goal of gene therapy is the targeted delivery of therapeutic genes to defined
      tissues. One attractive target is the central nervous system as there are several
      neuronal degenerative diseases which may be amenable to gene therapy. At present
      there is a lack of delivery systems that are able to target genes specifically to
      neuronal cells. Multi-domain proteins were designed and constructed to facilitate
      the delivery of exogenous genes to neuronal cells. Neuronal targeting activity of
      the proteins was achieved by inclusion of the HC fragment of tetanus toxin
      (TeNT), a protein with well-characterised tropism for the central nervous system.
      The yeast Gal4 DNA-binding domain enabled specific binding of DNA while the
      translocation domain from diphtheria toxin (DT) was included to facilitate
      crossing of the endosomal vesicle. One multi-domain protein, containing all three
      of these domains, was found to transfect up to 8% of neuroblastoma N18-RE105
      cells with marker genes. Monitoring the transfection by confocal microscopy
      indicated that this protein-DNA transfection complex is to some extent localised
      at the cell surface, suggesting that further improvements to translocating this
      membrane barrier may yield higher transfection levels. The demonstration that
      this multi-domain protein can target genes specifically to neuronal cells is a
      first step in the development of novel vectors for the delivery of genes with
      therapeutic potential to diseased neuronal tissues.

PMID- 14668055
TI  - Use of block copolymers of poly(ortho esters) and poly (ethylene glycol) micellar
      carriers as potential tumour targeting systems.
AB  - Amphiphilic AB and ABA block copolymers have been prepared from poly (ortho
      esters) and poly (ethylene glycol). Such block copolymers readily form micellar
      dispersions in water, or buffers. The CMC is in the range of 3 x 10(-4)-5 x 10(
      4) g/l which is a value low enough to assure retention of micelle integrity upon
      intravenous injection. The size, as determined by dynamic light scattering was in
      the 40-70 nm range. The micelles can be stored in lyophilized form for at lest 8
      months and easily reconstituted to the original properties. The micelles are
      stable in PBS at pH 7.4 and 37 degrees C for 3 days and in a citrate buffer at pH
      5.5 and 37 degrees C for 2 h. Stability in the presence of bovine serum albumin
      depends on the structure of the block copolymer and especially the length of the
      POE block.

PMID- 14668056
TI  - Activity of hydrolytic enzymes in tumour cells is a determinant for anti-tumour
      efficacy of the melphalan containing prodrug J1.
AB  - Recently, we presented a series of melphalan containing di- and tripeptides with
      high cytotoxic activity and J1 (l-melphalanyl-p-l-fluorophenylalanine ethyl
      ester) was identified as one of the most interesting compounds. It was speculated
      that the increased activity compared to melphalan itself, demonstrated both in
      vitro and in vivo, resided in increased transport over the tumour cell membrane
      and/or hydrolytic cleavage and liberation of melphalan inside the cells. Indeed,
      overexpression of hydrolytic enzymes like peptidases, esterases and proteases has
      been described in several types of human malignancies, thus providing a target
      for selective chemotherapy. In this work, the details of the increased activity
      was further investigated and potential tumour selectivity is discussed. The
      intracellular delivery of melphalan is investigated in detail using peptidase
      resistant dipeptide derivatives, by enzyme inhibitors and probes for enzymatic
      activity and by studying the time dependency of drug effect as well as
      intracellular drug concentrations (cellular pharmacokinetics). The results show
      that the activity of the dipeptide mustards is highly dependent on intracellular
      hydrolysis, which result in rapid intracellular release of the alkylating unit
      (i.e. free melphalan) in cells with high enzymatic activity. The maximum
      intracellular melphalan concentration following J1 exposure was reached already
      after 15 min, thereafter declining with a half-life of approximately 1 h. This
      rapid intracellular loading resulted in less reduction of activity for J1 than
      for melphalan and six other standard drugs when human tumour cell lines were
      exposed to the drugs for a limited time (simulating short half-life in vivo).
      Peptidase inhibitors inhibited the activity and intracellular release of
      melphalan, and dipeptide derivatives designed to resist the action of peptidases
      was less active than the corresponding normal dipeptide.

PMID- 14668057
TI  - Development of enteric-coated pectin-based matrix tablets for colonic delivery of
      theophylline.
AB  - The present work was aimed at developing a new colonic drug delivery system which
      takes advantage of the combined approaches of a specifically colon-biodegradable
      pectin matrix with a pH-sensitive Eudragit S100 polymeric coating. The developed
      system was able to suitably retard the onset of drug release and to provide a
      colon-specific delivery, thus overcoming the problems of pectin solubility in the
      upper gastrointestinal tract and low site-specificity of simple pH-dependent
      systems. Due to the poor compactability properties of pectin, it was used in
      mixture with Emdex, a hydrophilic directly-compressible material, in order to
      make it possible to prepare tablets by direct compression. Theophylline (TP) was
      used as model drug due to its suitable pharmacokinetic properties for colonic
      delivery and good absorption in the large intestine. The effects of varying the
      type of pectin (low and high methoxylated, or amidated), the pectin:Emdex ratio
      and the level of the pH-dependent polymeric coating on drug release behavior were
      investigated. Release tests were performed using sequential liquids simulating
      the physiological variation of pH and the effect of the presence or not of
      pectinolytic enzymes into the simulated colonic medium was evaluated. Thirty
      percent (w/w) was the the minimum content of Emdex for obtaining directly
      compressible tablets with sufficient hardness to withstand the coating process
      and 27% (w/w) was the minimum coating amount for obtaining an adequate lag time
      before the onset of drug release. After lag time, linear nearly zero-order
      profiles were obtained whose slope (i.e. the drug release rate) depended on both
      the Emdex content and the pectin type. Comparison of the results obtained in the
      presence or not of pectynolitic enzymes allowed selection of the high
      methoxylated pectin as the most interesting candidate for specific colonic
      delivery since it was the least water-soluble and the most susceptible to
      enzymatic degradation, thus assuring a greater site-specificity of drug release.
      Finally, the importance of using appropriate dissolution test conditions to
      adequately characterize the drug release profiles from delivery systems endowed
      with a microflora-activated drug release triggering mechanism has been
      demonstrated.

PMID- 14668058
TI  - Effects of membrane type and liquid/liquid phase boundary on in vitro release of
      ketoprofen from gel formulations.
AB  - The aim of this study was to test the hypothesis that the most appropriate model
      for studying the diffusional release of an active from a topical formulation is
      one in which the membrane offers minimal resistance to release and involves a
      receptor phase that presents the least possible interfacial discontinuity. Using
      ketoprofen as the active, a series of simple gels were prepared consisting of
      PEG400 thickened with Cabosil M5. Using Franz-type diffusion cells, three
      different types of membrane (two porous and one non-porous) were compared, as
      were receptor phases of PEG400 (component of formulation) and PBS. Of the
      membranes tested only 0.2 microm nylon provided consistent first order kinetics
      for a range of gel consistencies, indicating negligible influence of the
      membrane. The non-porous silicone membrane did not show first order kinetic
      profile confirming the diffusional nature of such a membrane. From the non
      thickened formulations, diffusional release into a receptor phase of PEG400 was
      some 3x that into PBS, whereas from the formulation thickened with 5% Cabosil M5,
      diffusional release into a receptor phase of PEG400 was 6x lower than that into
      PBS. Diffusional release into PBS did not follow first order kinetics while
      diffusion into PEG400 did, suggesting that the existence of a discontinuity
      affected the release process. Although the importance of zero-resistance
      membranes is of perhaps obvious importance, it is often not stated in the
      literature. The existence of phase/hydrodynamic boundaries in release studies can
      be a source of significant inaccuracy.

PMID- 14668059
TI  - Phorbol esters alter alpha4 and alphad integrin usage during eosinophil adhesion
      to VCAM-1.
AB  - We examined the effect of the protein kinase C activator phorbol-12-myristate-13
      acetate (PMA) on the human eosinophil adhesion molecule phenotype and attachment
      to VCAM-1 via alpha4 and alphad integrins under static and flow conditions. PMA
      increased surface expression of alphad integrins and decreased alpha4 integrin
      expression. Under static conditions, eosinophils bound well to VCAM-1, primarily
      via alpha4beta1 integrins, with a minor alphadbeta2 integrin component.
      Unexpectedly, PMA-stimulated eosinophils bound equally well to VCAM-1 and albumin
      in a temperature- and divalent cation-dependent manner, yet adhesion was
      independent of beta1 and beta2 integrins. Under flow conditions, eosinophils
      readily attached to VCAM-1, and adhesion was inhibited by both alpha4 and alphad
      mAbs (95 and 50% inhibition, respectively). Many fewer PMA-stimulated eosinophils
      bound to VCAM-1 under flow conditions, but both alpha4 and alphad mAbs inhibited
      adhesion equally. Thus, PMA alters eosinophil integrin expression and the
      relative contributions of alpha4 and alphad integrins during attachment to VCAM
      1.

PMID- 14668060
TI  - The beta3 integrin gene is expressed at high levels in the major haematopoietic
      and lymphoid organs, vascular system, and skeleton during mouse embryo
      development.
AB  - Integrins are a family of cell surface molecules that mediate the attachment of
      cells to the extracellular matrix (ECM). These alphabeta heterodimers are
      involved in many biological processes. We used northern blotting and in situ
      hybridization to study the pattern of beta3 integrin gene expression during mouse
      embryogenesis. Northern blotting detected two species of beta3 mRNA from 7 to 17
      days post coitum (dpc). These transcripts were abundant in the adult testis,
      kidney, liver, spleen, and heart. In situ hybridization experiments detected high
      levels of beta3 in the major haematopoietic and lymphoid organs: yolk sac, liver,
      and thymus. Moreover, beta3 transcripts were also detected in the vascular
      system, where beta3 integrin probably plays a key role in angiogenesis and
      vasculogenesis. We also detected a hybridization signal in the gut, the
      bronchioles of the lungs, and the bladder wall. beta3 transcripts were also
      present in the medullary regions of the adrenal glands and in the developing
      skeleton. Our study shows that beta3 gene expression is not restricted to the
      liver and gut during mouse development. We also detected beta3 integrin mRNA in
      the yolk sac, vessels, lung, bladder, and developing bones. Our data suggest that
      beta3 integrin plays a key role in many important physiological processes like
      haematopoiesis, angiogenesis, phagocytosis, and bone resorption.

PMID- 14668061
TI  - ICAM-1 mediated tumor-mesothelial cell adhesion is modulated by IL-6 and TNF
      alpha: a potential mechanism by which surgical trauma increases peritoneal
      metastases.
AB  - Peritoneal metastases frequently occur in different gastrointestinal cancers and
      have a poor prognosis. It is known that surgical injury promotes tumor growth and
      local recurrence rates and also the degree of surgical trauma correlated with the
      amount of tumor implantation into the peritoneum. The mechanism that mediates
      tumor cell adhesion to the mesothelium is not fully understood. This study
      investigates the role of ICAM-1, an important mediator of trans-mesothelial
      leucocyte migration, in tumor-mesothelial interactions as the initial step in the
      development of peritoneal recurrence using an in vitro model incorporating
      mesothelial cell monolayer derived from omental samples. We also investigate how
      the cytokines interleukins 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha)
      modulate this process. We demonstrate that ICAM-1 blockade reduces the ability of
      both pancreatic and colonic cancer cell lines to adhere to the mesothelium.
      Preincubation of the mesothelial cell monolayer with either IL-6 or TNF-alpha
      enhances tumor cell adhesion, and this is associated with an increased expression
      of ICAM-1. Mesothelial CD44 expression, which has previously been implicated in
      this process, was unaffected by these cytokines. The use of an inhibitory
      monoclonal antibody against ICAM-1 attenuated the enhanced adhesion mediated by
      IL-6 or TNF-alpha. This study suggests that mesothelial ICAM-1 plays a role in
      the adhesion of tumor cells to the peritoneum in the development of peritoneal
      metastases.

PMID- 14668062
TI  - IGF-1 modulation of rat cardiac fibroblast behavior and gene expression is age
      dependent.
AB  - The collagenous extracellular matrix (ECM) forms a stress-tolerant network that
      is essential for proper function of the vertebrate heart. Profound changes have
      been detected in the interstitial ECM concurrent with developmental and disease
      processes of the heart. These alterations in either the organization or
      accumulation of ECM components markedly affect myocardial function. Studies have
      shown that a number of biochemical factors, including angiotensin II,
      transforming growth factor-beta, and insulin-like growth factors, modulate
      collagen expression by heart fibroblasts, however, few studies have examined the
      differential effects of these factors on fibroblasts from animals of different
      physiological backgrounds. The present studies were carried out to determine
      whether cardiac fibroblasts isolated from different aged animals (fetal,
      neonatal, and adult) have diverse responses to insulin-like growth factor-1 (IGF
      1). Fibroblasts isolated from fetal, neonatal, and adult rat hearts were treated
      with IGF-1, and several downstream responses were measured, including collagen
      gel contraction, adhesion to ECM, and expression of interstitial collagen and
      integrins. IGF-1 affected these parameters to different degrees, depending on the
      age of the animal from which the fibroblasts were isolated. These experiments
      indicate that IGF-1 is a potent modulator of fibroblast behavior in general;
      however, significant differences are apparent in the responsiveness of cells to
      this growth factor depending on the age of the animal of origin. Future
      experiments will be directed at determining how the in vivo chemical and
      biomechanical environment affects the response of heart fibroblasts to growth
      factors such as IGF-1.

PMID- 14668064
TI  - Cigarette smoking among Chinese Americans and the influence of linguistic
      acculturation.
AB  - Less acculturated Chinese Americans experience cultural and language barriers.
      The present study assessed the relationship between linguistic aspects of
      acculturation and cigarette smoking among Chinese Americans. A cross-sectional,
      self-administered survey was administered to a consecutive sample of 541 Chinese
      American adults (aged 18 years or older) attending four pediatric, medical, or
      dental practices located in Philadelphia's Chinatown from November 2000 to
      February 2001. Linguistic acculturation was measured by adapting a reliable and
      valid acculturation scale developed for Southeast Asians. English and Chinese
      language proficiency subscales were utilized to analyze the association between
      language proficiency and current smoking. Whereas 25% of Chinese American men
      reported current smoking, only 3% of Chinese American women reported current
      smoking. Chinese American men with lower English proficiency reported
      significantly higher rates of current smoking compared with Chinese American men
      with a higher level of English proficiency (33% vs. 18%, p<.01). Less English
      proficient Chinese American male smokers were less likely to have received advice
      from a physician to quit smoking (50% vs. 85%, p=.01). In multivariate analysis,
      increased English proficiency was associated with decreased odds of current
      smoking (OR=0.38, 95% CI=0.16-0.89) among Chinese American men after controlling
      for confounding variables. In conclusion, higher English proficiency was
      associated with decreased current smoking among Chinese American men. Chinese
      American men with limited English proficiency should especially be targeted for
      tobacco control interventions. Further research is needed to assess whether
      acculturation is associated with smoking among Chinese American women and with
      use of smoking cessation treatments and services by Chinese American smokers.

PMID- 14668065
TI  - Platelet monoamine oxidase B activity changes across 31 days of smoking
      abstinence.
AB  - Although recent studies demonstrate that tobacco cigarette smoke substantially
      inhibits both central nervous system and blood platelet monoamine oxidase (MAO)
      activity, little is known about the time course of MAO increases after smoking
      cessation. Therefore, changes in platelet MAO-B activity and mood were assessed
      before and at multiple times after quitting smoking. Quitting smoking was
      associated with a significant (22%) increase in MAO activity by day 3 and with a
      maximum increase (about 50%) by day 10 that was maintained through day 31 of
      abstinence. However, abstinence-related increases in depressive mood peaked at
      day 2 of abstinence, a week more rapidly than the peak increase in MAO-B
      activity. Neither mood nor MAO-B activity returned to baseline or smoking control
      levels across the 31-day abstinence period. The asynchrony of increased negative
      affect and MAO-B activity during the first few days of abstinence may reflect any
      of several possibilities. First, the duration of the platelet life cycle may not
      reflect central MAO-B or MAO-A activity. Second, MAO-B may not contribute to or
      index mood changes during the first days of abstinence though it may contribute
      to protracted abstinence-induced negative affect. These findings are discussed in
      terms of the hypothesis that platelet MAO activity reflects central nervous
      system MAO changes that promote increased depressive affect resulting from
      smoking abstinence.

PMID- 14668066
TI  - Increasing readiness to stop smoking in women undergoing cervical screening:
      evaluation of two leaflets.
AB  - This study evaluated the impact of informing women smokers of the link between
      smoking and cervical cancer. Women smokers aged 20-64 years from two general
      practices in the United Kingdom were randomly assigned to receive an extended
      leaflet, a brief leaflet, or no leaflet. Both leaflets informed women of the
      threat of cervical cancer, how stopping smoking would decrease their
      vulnerability to it, and the effectiveness of smoking cessation services. The
      extended leaflet included an elaborated explanation of how smoking adversely
      affects the cervix. Questionnaires were completed by 172 women. The main outcome
      was readiness to stop smoking within the next 6 months. Secondary outcomes were
      perceptions of severity and vulnerability to cervical cancer, beliefs about the
      effectiveness of reducing susceptibility by stopping smoking, and self-efficacy
      in stopping smoking. Women sent the briefer leaflet were more likely to be ready
      to stop smoking within the next 6 months compared with those sent the extended
      leaflet (75% vs. 46%, 95% CI=11%-48%) and those not sent a leaflet (75% vs. 40%,
      95% CI=19%-52%). Compared with smokers not sent a leaflet, those sent either of
      the two leaflets perceived their vulnerability to cervical cancer as higher and
      had greater expectations that stopping smoking would reduce this risk. In
      conclusion, providing women with brief written information about the link between
      smoking and cervical cancer increases their readiness to stop smoking. The impact
      on smoking cessation of combining such information with advice from health
      professionals conducting cervical screening needs to be evaluated.

PMID- 14668067
TI  - Characterization of chronic nicotine exposure on the survival of the spastic Han
      Wistar rat.
AB  - Excitotoxicity has been implicated as a mechanism of cell death in many
      neurodegenerative disorders. Cell culture studies have shown that neuroprotection
      can be induced by preincubation with the acetylcholine agonist nicotine. We
      investigated the possible neuroprotective effects of nicotine in the spastic Han
      Wistar rat, which suffers from glutamate excitotoxicity affecting two central
      nervous system regions: The hippocampus and the cerebellum. To investigate
      nicotine's possible neuroprotection, we treated 25-day-old mutant and normal
      siblings with 50-75 mg/l nicotine in their drinking solutions. The 75-ml/l dose
      significantly improved motor activity and increased longevity of the mutants
      (p<.05). To assess whether nicotine protected individual neurons, we performed
      hematoxylin and eosin (H&E) staining of brain sections. The histological data
      indicated that nicotine increased the survival of Purkinje cells in the mutants
      by as much as 50% but did not prevent cell death. To investigate whether the
      neuroprotection by nicotine was due to changes in nicotinic receptor expression,
      we performed immunohistochemical studies by staining for the alpha 3, alpha 4,
      and alpha 7 receptor subunits in mutant and normal rats. The alpha 4 subunit was
      upregulated by nicotine treatment in the cerebellum and was noted to have lower
      levels throughout the hippocampus of mutant animals. The alpha 3 and alpha 7
      subunits showed no change in expression among all groups.

PMID- 14668068
TI  - The meanings of smoking among Chinese American and Taiwanese American college
      students.
AB  - Smoking on college campuses in the United States has increased at an alarming
      rate since the early 1980s. Smoking rates differ according to students'
      culture/ethnicity and are linked to levels of acculturation. Little is known
      concerning the determinants of smoking in college populations. To develop
      effective smoking interventions targeting college smoking, an understanding of
      why these populations are taking up tobacco is vital. The meanings with which
      adolescents imbue smoking have been related to smoking behaviors in adolescent
      populations. Meanings of particular behaviors are strongly influenced by cultural
      background and acculturation. Meanings of smoking have not yet been investigated
      in culturally diverse college-aged populations. This in-depth qualitative
      investigation examined the meanings of smoking among Chinese and Taiwanese
      students, who are among the fastest growing populations on U.S. college campuses.
      These groups were selected to attempt to trace why Asian American students are at
      higher risk for increased smoking prevalence than any other ethnic group.
      Personal, functional, and socially relevant meanings emerged as powerful factors
      that direct smoking behaviors. Because smoking is not accepted as readily in the
      United States as it is in China and Taiwan, subjects reported experiencing a
      profound shift in social norms after immigration, which led to a change in
      meanings of smoking. These changes in meanings precipitated changes in smoking
      behavior. Smokers reported reducing tobacco use or quitting altogether.
      Implications of these findings as they relate to patterns of smoking in Chinese
      American and Taiwanese American populations are discussed.

PMID- 14668069
TI  - Short-term adolescent nicotine exposure in rats elicits immediate and delayed
      deficits in T-lymphocyte function: critical periods, patterns of exposure, dose
      thresholds.
AB  - Prenatal nicotine exposure elicits lasting deficiencies in T-lymphocyte
      mitogenesis, and the period of vulnerability extends into adolescence, the stage
      at which smoking typically commences. We explored the importance of nicotine
      exposure patterns (continuous infusion vs. repeated subcutaneous injections),
      dose-effect relationships, and specificity of the effects. Adolescent rats were
      given nicotine infusions for 1 week beginning on postnatal day (PN) 30, using a
      regimen (6 mg/kg/day) that produces plasma nicotine levels (25 ng/ml) similar to
      those in smokers; another group received 2 mg/kg/day. At the end of the infusion
      period (PN37), T-lymphocyte mitogenic responses to concanavalin A were deficient
      in the group receiving 6 mg/kg/day; values for the 2 mg/kg/day group were
      intermediate between controls and the 6 mg/kg/day group. One week after the
      termination of nicotine treatment, responses returned to normal, only to reemerge
      in young adulthood (PN65), at which stage adverse effects were significant even
      for the group that received 2 mg/kg/day. In contrast to the T-cell alterations, B
      lymphocyte responses were unaffected. Administering the same total doses of
      nicotine by twice-daily subcutaneous injections over the 1-week treatment period
      (1 or 3 mg/kg per injection) did not evoke deficits in responses of either T
      cells or B-cells, even though the high dose produced overt systemic toxicity and
      persistent weight loss. Our results indicate that adolescent nicotine exposure,
      even at levels below those associated with active smoking, elicits selective
      deficits in T-lymphocyte function. Although short-term adaptations may correct
      the effects, deficits reemerge in young adulthood despite cessation of nicotine
      exposure.

PMID- 14668070
TI  - Common factors across acute subjective effects of nicotine.
AB  - Nicotine intake acutely induces many different subjective mood effects, which may
      be critical to understanding nicotine reinforcement. Some of these effects may
      cluster together, perhaps reflecting common underlying mechanisms (e.g.,
      catecholamine release). In this study of 93 smokers, ex-smokers, and nonsmokers,
      we conducted factor analyses of responses to a battery of subjective measures (23
      visual-analog scale items and Profile of Mood States [POMS] scales) following
      acute nicotine nasal spray administration. The goal was to identify homogeneous
      clusters among these diverse effects of nicotine. A subject's response to
      nicotine on each measure was determined by the slope of his or her dose-response
      curve (0, 10, 20 microg/kg nicotine). Results of factor analyses identified five
      factors, labeled "head rush" (head rush, buzzed, lightheaded, jittery), "positive
      affect" (comfortable, satisfied, relaxed, etc.), "negative affect" (anger,
      depression, tension), "fatigued" (tired, sedated, fatigue), and "energized"
      (stimulated, vigor). The factor structure was consistent between smoking status
      groups. However, as expected, groups differed on mean factor scores for head
      rush, positive affect, and energized, perhaps reflecting tolerance to these
      effects of nicotine. Although these specific findings require replication, they
      suggest that acute subjective responses to nicotine can be captured by a few
      common factors, potentially simplifying this assessment. Similar research may
      provide directions for exploring potential mechanisms responsible for these broad
      subjective effects of nicotine.

PMID- 14668071
TI  - The consistency of acute responses to nicotine in humans.
AB  - Nicotine has many acute subjective, physiological, and behavioral effects in
      humans, some of which may explain why nicotine produces dependence. Individual
      differences in the magnitude of these effects (i.e., nicotine sensitivity) are of
      interest to many researchers, such as those examining vulnerability to dependence
      and processes related to chronic tolerance. However, such characterization of
      individual differences depends on the consistency of the observed responses, and
      the consistency of acute effects of nicotine in humans has not been studied
      systematically. We examined the consistency of the acute effects of the same dose
      of nicotine administered by nasal spray across multiple drug administration
      trials, within as well as between sessions. Subjective (i.e., self-reported
      effects), cardiovascular, and performance measures were assessed following each
      of four dosing trials of nicotine (20 microg/kg) on three sessions and of placebo
      on one session. For those measures in which the main effect of nicotine vs.
      placebo was significant, intraclass correlations were calculated for different
      sets of trials across different numbers of sessions. Our objective was to
      determine whether the consistency of responses declined when those responses were
      based on smaller numbers of trials or sessions, in an effort to guide future
      research in this area. Results indicated that the consistency of nicotine effects
      is generally high, even across trials within just one session. Additional
      research is needed to determine the generalizability of these findings to other
      methods of nicotine administration, including smoking, and to clarify the extent
      to which this consistency reflects characteristic consistency of the
      pharmacological actions of nicotine per se vs. consistency of nonspecific
      responses to the drug administration procedure.

PMID- 14668072
TI  - Surveillance of smokeless tobacco nicotine, pH, moisture, and unprotonated
      nicotine content.
AB  - Smokeless tobacco is a complex chemical mixture, including not only the
      components of the tobacco leaf but also chemicals added during the manufacturing
      process. Smokeless tobacco contains the addictive chemical nicotine and more than
      20 cancer-causing chemicals, including the potent tobacco-specific nitrosamines.
      The National Toxicology Program of the National Institutes of Health has
      concluded that oral use of smokeless tobacco is a human carcinogen. Therefore,
      smokeless tobacco is not a safe alternative to cigarettes. In fact, smokeless
      tobacco use begins primarily during early adolescence and can lead to nicotine
      dependence and increased risk of becoming a cigarette smoker. Under the
      Comprehensive Smokeless Tobacco Health Education Act of 1986 (15 U.S.C. 4401 et
      seq., Pub. L. 99-252), tobacco manufacturers report annually to the Centers for
      Disease Control and Prevention (CDC) on the total nicotine, unprotonated
      nicotine, pH, and moisture content of their smokeless tobacco products. This
      information is considered "trade secret," or confidential, in accordance with 5
      U.S.C. 552(b)(4) and 18 U.S.C. 1905 and cannot be released to the public. In an
      effort to provide consumers and researchers with information on the nicotine
      content of smokeless tobacco, CDC arranged for the analysis of popular brands of
      smokeless tobacco. The results of this CDC study show that pH is a primary factor
      in the amount of nicotine that is in the most readily absorbable, unprotonated
      form. Furthermore, this study found that the brands of moist snuff smokeless
      tobacco with the largest amount of unprotonated nicotine also are the most
      frequently sold brands.

PMID- 14668073
TI  - The effect of methoxsalen on nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK) metabolism in vivo.
AB  - Nicotine is metabolized to the inactive metabolite cotinine by cytochrome P450
      2A6. NNK, or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, is a potent
      procarcinogen shown to be activated to a reactive mutagenic metabolite by the
      enzyme CYP2A6. We studied the effect of inhibiting CYP2A6 on smoking behavior and
      metabolism of the procarcinogen NNK. In study 1, abstinent smokers (n=7) received
      methoxsalen (a potent CYP2A6 inhibitor), 30-50 mg orally, one-half hour before
      three subcutaneous nicotine injections (31 microg/kg) were given at hourly
      intervals. Methoxsalen increased mean plasma nicotine by 47% (p<.01) and mean
      nicotine area under the curve (AUC) by 63% (p<.0001); and decreased nicotine
      clearance by 39% (p<.0001), relative to placebo. In study 2, smokers (n=11) were
      told to maintain their same number of cigarettes smoked while receiving
      methoxsalen, 10 mg orally three times daily for 3 days. On day 3 of methoxsalen
      treatment, a 29% increase in plasma nicotine/expired-air CO (an index of smoke
      exposure) (p=0.03) was observed. Urinary levels of trans 3'-hydroxycotinine
      (metabolized by CYP2A6 from cotinine) also were decreased (p<.0001), and
      significantly more NNK was metabolized to the inactive NNAL-glucuronide (1.04+/
      0.54 pmol/mg on day 1 to 1.37+/-0.74 pmol/mg on day 4, p<.01) relative to
      placebo. Thus, treatment with the CYP2A6 inhibitor methoxsalen in vivo increases
      the routing of NNK to the inactive NNAL-glucuronide and decreases smoking. CYP2A6
      inhibition may have potential as an exposure reduction or cessation strategy in
      tobacco dependence.

PMID- 14668074
TI  - An exploratory study of control of smoking in the home to reduce infant exposure
      to environmental tobacco smoke.
AB  - This study examined control of environmental tobacco smoke (ETS) exposure in the
      home by new mothers and identified factors related to the establishment of home
      smoking control rules. Pregnant women who, at 28 weeks gestation, reported they
      had not smoked in the past 28 days were enrolled in a randomized smoking
      cessation study. Telephone interviews were conducted at 6 weeks, 3 months, 6
      months, and 12 months postpartum. A Home Smoking Control Index, composed of four
      items (whether the mother smokes in the home, the partner smokes in the home,
      other household smokers are asked to smoke outside, and visitors who smoke are
      asked to smoke outside), was used to classify homes as having a home smoking
      policy in effect, no policy or an incomplete policy, or no policy needed.
      Sociodemographic variables and maternal self-efficacy were examined in relation
      to the index data among 325 women who had need to exercise control of smoking in
      the home: 63% had a home smoking policy in effect at 3 months, 60% at 6 months,
      and 64% at 12 months postpartum. Predictors of policy at 6 and 12 months included
      (a) having a policy in effect at the previous assessment, (b) confidence in
      limiting infant ETS exposure in the home, and (c) perceived difficulty in
      preventing exposure. Early establishment of a policy appears to be important for
      ensuring sustained infant ETS avoidance over time. The index measures key actions
      that influence infant exposure and warrants further testing for use in
      intervention trials.

PMID- 14668075
TI  - Bupropion SR and counseling for smoking cessation in actual practice: predictors
      of outcome.
AB  - To date, only one study has been published on individual characteristics
      associated with outcome following standard treatment with bupropion SR for
      smoking cessation. To investigate treatment outcome beyond the 6-week end-of
      treatment point, the present study examined characteristics associated with more
      clinically relevant smoking endpoints following treatment with bupropion SR in a
      large health care system. A total of 1,524 smokers (649 men and 875 women) of
      average age 45.1 years were randomized to receive one of four combinations of
      bupropion SR (150 or 300 mg) and behavioral counseling (tailored mailings or
      proactive telephone counseling) and assessed for point-prevalent smoking status
      at 3 and 12 months. Multiple logistic regression analyses of potential risk
      factors for 12-month point-prevalent smoking and for persistent smoking (point
      prevalent smoking at both follow-ups) following treatment were conducted for men
      and women combined and separately. Risk factors for smoking at both endpoints in
      the combined sample included treatment with tailored mailings, female gender,
      younger age, higher levels of tobacco dependence, shorter previous quit attempts,
      previous use of nicotine replacement therapy, and report of current depressive
      symptoms or lifetime depression. Risk factors for smoking following treatment
      identified in women only included treatment with the lower dose of bupropion SR,
      younger age, and higher perceived stress, whereas those that were unique to men
      included the presence of lifetime depression. The results are discussed in terms
      of their implications for the need for more effective treatments in general, and
      the role of individual differences in the likelihood of returning to smoking
      following treatment for quitting.

PMID- 14668076
TI  - Heavy smokers: a qualitative analysis of attitudes and beliefs concerning
      cessation and continued smoking.
AB  - In this qualitative analysis, we conducted intensive interviews of a group of
      heavy smokers to better understand psychosocial characteristics related to
      smoking and quitting. A total of 51 heavy smokers were recruited to participate
      in this study. In-depth interviews lasting 60-90 min explored factors related to
      smoking and attitudes toward cessation. N'Vivo was used to analyze the data. We
      modeled a number of factors related to heavy smoking in this population. A
      comprehensive model appeared to fit the data well. Key factors related to heavy
      smoking included those that promote smoking, those that influence quitting,
      perceptions of quitting, and explanations of failure. Along each of these
      dimensions, clusters of variables, such as the social environment, emotional
      identity, addiction, and physical health, emerged as being important in
      understanding the perceptions of heavy smokers when it comes to smoking and
      quitting. The models add important information to our understanding of heavy
      smokers. This work indicates that this sample of heavy smokers had many issues
      around smoking and quitting, including the perceived difficulty of quitting,
      physical and psychological addictions to smoke, reinforcement for smoking, and a
      tendency to procrastinate in quitting.

PMID- 14668077
TI  - Does the DRD2-Taq1 A polymorphism influence treatment response to bupropion
      hydrochloride for reduction of the nicotine withdrawal syndrome?
AB  - Bupropion hydrochloride is effective in promoting long-term abstinence from
      smoking and may reduce risk for relapse through attenuation of withdrawal
      symptoms and craving. Bupropion is a weak dopamine reuptake inhibitor, and
      individual genetic variation in the dopamine D2 receptor has been associated with
      nicotine dependence in case-control studies. Thirty smokers were randomly
      assigned to bupropion or placebo and interviewed using the Minnesota Nicotine
      Withdrawal Scale on two occasions: prior to starting medication and after 14 days
      on bupropion or placebo. The individual symptoms of craving, irritability, and
      anxiety were significantly reduced in the bupropion group, whereas no withdrawal
      symptoms were diminished in the placebo group. Within the bupropion group,
      subgroup analyses with stratification by genotype demonstrated that craving,
      irritability, and anxiety were significantly attenuated only among subjects with
      DRD2-Taq1 A2/A2 genotypes. In the DRD2-Taq1 A1/A1 and A1/A2 groups, no
      significant reduction was seen in any individual symptom of the nicotine
      withdrawal syndrome. These data suggest that bupropion attenuates specific
      symptoms of the nicotine withdrawal syndrome and that this effect may be modified
      by genotype for the dopamine D2 receptor.

PMID- 14668078
TI  - Secondhand smoke and earaches in adolescents: the Florida Youth Cohort Study.
AB  - The association between second-hand smoke exposure and adolescent middle ear
      problems has not been examined. A random sample stratified by region was drawn
      from a list that included approximately 40% of all Florida households with
      children in grades 4-7. A total of 785 Florida adolescents initially enrolled in
      the 4th-7th grade participated in three telephone interviews conducted over a 24
      month period. At the round 3 interview, 10.3% of participants reported one or
      more earaches within the previous 30 days. Several second-hand smoke exposure
      questions asked at each of the three interviews were associated with the number
      of reported earaches. Stepwise polytomous logistic regression indicated that
      parental smoking inside the home reported at the round 3 interview was associated
      with the number of reported earaches (OR=3.11, 95% CI=1.70-5.66). Once this
      variable was selected, none of the other second-hand smoke exposure variables
      offered additional predictive value (p>.1). None of the non-second-hand smoke
      exposure variables, including the participant's own history of tobacco use, had
      any association with the reporting of earaches (p>.05). Second-hand smoke
      exposure is associated with self-reported earaches in adolescents. These findings
      should be replicated in a study in which clinical measures of middle ear function
      are performed.

PMID- 14668079
TI  - Labetalol treatment enhances the attenuation of tobacco withdrawal symptoms by
      nicotine in abstinent smokers.
AB  - The noradrenergic system may mediate some of the acute physiological effects of
      nicotine and nicotine withdrawal symptoms. This study examined the effects of
      labetalol, an alpha- and beta-adrenergic receptor blocker, on acute physiological
      and subjective effects of intravenous nicotine and on tobacco withdrawal
      symptoms. Five female and four male smokers participated in a double-blind,
      placebo-controlled, crossover study. Following overnight abstinence from smoking,
      subjects were treated orally with a single 100- or 200-mg dose of labetalol or
      placebo in each of three experimental sessions. Two hours after the medication
      treatment, subjects received an intravenous injection of 15 microg/kg nicotine.
      The nicotine-induced increases in heart rate were attenuated with the high dose
      of labetalol. No treatment effects were found for systolic or diastolic blood
      pressure changes. For the subjective effects of nicotine, treatment with both
      high and low doses of labetalol enhanced the ratings of "head rush" and "drug
      strength." The attenuation of tobacco withdrawal symptoms following intravenous
      nicotine administration was significantly greater with high-dose labetalol
      treatment, compared with placebo. These results support the proposed role of
      adrenergic receptors in nicotine withdrawal symptoms. The utility of adrenergic
      blockers, in combination with nicotine replacement therapies, for smoking
      cessation needs to be examined further in controlled clinical trials.

PMID- 14668080
TI  - Sex-selective hippocampal alterations after adolescent nicotine administration:
      effects on neurospecific proteins.
AB  - Nicotine is a neuroteratogen that targets cell development and synaptic function
      into adolescence, when smoking typically commences. We used a rat model of
      adolescent nicotine exposure to characterize the types of cells involved in
      hippocampal alterations. Nicotine was given to adolescent rats by minipump
      infusions from postnatal day (PN) 30 to PN47.5, using a dose rate (6 mg/kg/day)
      that replicates the plasma nicotine levels found in smokers. We examined specific
      neuronal and astrocyte proteins in the posttreatment period (PN50, PN60), when
      deficits in neurotransmission first appear: glial fibrillary acidic protein
      (GFAP), a marker for astrocytes; neurofilament 68-kDa protein (NF68), which is
      concentrated in the neuronal perikaryon and proximal neurites; and neurofilament
      200-kDa protein (NF200), which is found in axonal projections distal to the
      perikaryon. Adolescent nicotine treatment evoked a significant decrease across
      all three markers, with the effect restricted to females and showing
      intensification between PN50 and PN60. These changes correspond to the sex
      selectivity and temporal course over which other biomarkers indicate hippocampal
      cell damage and alterations in synaptic function. We conclude that administration
      of nicotine to adolescent rats alters neuroproteins in the female hippocampus
      during withdrawal, effects that could contribute to neurobehavioral deficits.

PMID- 14668081
TI  - A softer view of hardening.

PMID- 14668082
TI  - What's new in nicotine & tobacco research?

PMID- 14668083
TI  - Transdisciplinary tobacco use research.

PMID- 14668084
TI  - Facilitating transdisciplinary research: the experience of the transdisciplinary
      tobacco use research centers.
AB  - Cigarette smoking is the largest preventable cause of death and morbidity in the
      United States. Heightened recognition of this public health concern has led
      researchers from multiple and varied disciplines to address this complex and
      multidimensional behavior. The need for an alternative research paradigm,
      focusing on a transdisciplinary approach that integrates work across disciplines
      in order to advance the field most quickly, has been identified. This recognized
      need led to the development of the Transdisciplinary Tobacco Use Research Centers
      (TTURC) initiative, funded jointly by the National Cancer Institute, the National
      Institute on Drug Abuse, and The Robert Wood Johnson Foundation. This paper
      discusses the formation and early implementation stages of the initiative,
      including meetings that led to the development of the TTURCs, funders' and
      research centers' perspectives on implementation, and early observations about
      the products of the initiative.

PMID- 14668085
TI  - Evaluating transdisciplinary science.
AB  - The past two decades have seen a growing interest and investment in
      transdisciplinary research teams and centers. The Transdisciplinary Tobacco Use
      Research Centers (TTURCs) exemplify large-scale scientific collaborations
      undertaken for the explicit purpose of promoting novel conceptual and
      methodological integrations bridging two or more fields. Until recently, few
      efforts have been made to evaluate the collaborative processes, and the
      scientific and public policy outcomes, of such centers. This manuscript offers a
      conceptual framework for understanding and evaluating transdisciplinary science
      and describes two ongoing evaluation studies covering the initial phase of the
      TTURC initiative. The methods and measures used by these studies are described,
      and early evaluative findings from the first 4 years of the initiative are
      presented. These data reveal progress toward intellectual integration within and
      between several of the TTURCs, and cumulative changes in the collaborative
      behaviors and values of participants over the course of the initiative. The data
      also suggest that different centers may follow alternative pathways toward
      transdisciplinary integration and highlight certain environmental,
      organizational, and institutional factors that influence each center's readiness
      for collaboration. Methodological challenges posed by the complexities of
      evaluating large-scale scientific collaborations (including those that
      specifically aspire toward transdisciplinary integrations spanning multiple
      fields) are discussed. Finally, new directions for future evaluative studies of
      transdisciplinary scientific collaboration, both within and beyond the field of
      tobacco science, are described.

PMID- 14668086
TI  - Training the transdisciplinary scientist: a general framework applied to tobacco
      use behavior.
AB  - The complexity of public health problems, including the problem of tobacco use
      behaviors, calls for formal efforts to train transdisciplinary scientists. These
      scientists can approach problems by using new conceptual frameworks and
      methodological tools that integrate different disciplinary perspectives.
      Transdisciplinary training focuses on developing strong scientists with superb
      core skills while protecting against creating scientists who are "jack of all
      trades, master of none." Transdisciplinary training is relatively new, with no
      accepted training model in place. In this paper, we provide a general framework
      for transdisciplinary training at the advanced graduate and postgraduate levels,
      with particular reference to tobacco use behaviors. We identify the core
      attitude, knowledge, and skills competencies that are essential to conducting
      tobacco use research with a transdisciplinary approach. We outline the structural
      components of transdisciplinary training that allow for the development of the
      competencies and discuss what facilitates the transdisciplinary training process.
      We also discuss the numerous challenges and obstacles to transdisciplinary
      training. These include the readiness of early-career trainees to undergo
      transdisciplinary training, professional development risks taken by trainees,
      administrative and budgetary obstacles inherent in traditional academic
      institutional structures, and the limited opportunities established scientists
      have for transitioning their research programs in a transdisciplinary direction.
      If these obstacles can be overcome, the potential exists for a new generation of
      transdisciplinary scientists to be trained and be well positioned to make
      important and unique advances in our understanding of tobacco use and other
      public health problems.

PMID- 14668087
TI  - Intergenerational transmission of tobacco use and dependence: a transdisciplinary
      perspective.
AB  - Numerous questions remain regarding the intergenerational transmission of tobacco
      use and dependence, and some of these questions are best approached from a
      transdisciplinary perspective. For example, considering both genetic and
      environmental influences on cigarette smoking promises to be a fruitful venue for
      future investigations. In this paper, we consider the evidence regarding
      intergenerational influences on the transmission of tobacco use and nicotine
      dependence in both humans and animal models; our focus will be on genetic
      influences, in utero exposure to nicotine, and some postnatal influences.
      Research gaps that exist between scientific disciplines are highlighted, and some
      directions for future research are suggested.

PMID- 14668088
TI  - Tobacco use across the formative years: a road map to developmental
      vulnerabilities.
AB  - Different vulnerabilities are launched or play a more active role at different
      developmental stages and different ages. Furthermore, the interplay between
      developmental and biological, psychosocial, and environmental vulnerabilities is
      expected to differ across stages of smoking. This article focuses on the
      intersection of vulnerability associated with adolescence with tobacco-use
      vulnerability resulting from biological, psychological, and environmental
      characteristics of an adolescent. Recommendations include the following: (a)
      Effectively treat childhood and adolescent behavioral and emotional disorders
      that place adolescents at risk; (b) target programs toward specific high-risk
      subgroups; (c) incorporate training in self-control, affect regulation, and
      healthy coping strategies into educational programs and extracurricular
      activities; (d) encourage youth to develop healthy sources of success and
      satisfaction; (e) encourage communities and states to launch environmental,
      policy, and regulatory initiatives to protect youth from tobacco; (f) consider
      bold initiatives that will require fundamental changes in public attitudes,
      including monetary rewards for nonsmoking, heightened penalties for facilitating
      and engaging in underage smoking, and government subsidies for substitute
      pharmacological agents.

PMID- 14668089
TI  - Transdisciplinary science applied to the evaluation of treatments for tobacco
      use.
AB  - Transdisciplinary research involves the integration of measures and methods
      across diverse response systems and levels of analysis, with that integration
      occurring via a synthesis of theories and models of different scientific
      disciplines. This paper first discusses the need for transdisciplinary research.
      The paper then articulates a model to guide the comprehensive evaluation of
      treatments for tobacco use and discusses how transdisciplinary research might be
      integrated into this treatment evaluation model. The potential benefits and costs
      of a transdisciplinary approach are discussed, along with selected research
      projects from the Transdisciplinary Tobacco Use Research Centers.

PMID- 14668090
TI  - Exploring the cultural context of tobacco use: a transdisciplinary framework.
AB  - Understanding culture is an essential key to reducing tobacco use.
      Conceptualizations of culture vary across scientific disciplines and theoretical
      orientations. Because of the complexity of the causes and effects of tobacco use,
      no single discipline has sufficient capacity to undertake a comprehensive
      approach to studying culture and tobacco. Transdisciplinary research offers a
      means of bridging disciplinary perspectives. This paper reviews epidemiological
      data on observed variation in smoking patterns across national groups,
      ethnicities and genders, and presents reasons for studying culture in tobacco
      control research. We discuss and contrast conceptualizations and specific
      definitions of culture and identify aspects of each conceptualization that are
      relevant to research on tobacco. We present a multilevel, multidimensional
      conceptual framework for transdisciplinary research teams to use to think
      together about the influence of culture on tobacco and of tobacco on culture. The
      framework challenges researchers to think about how the sociocultural context
      influences tobacco use at micro, meso, and macro levels. Finally, we offer
      suggestions for improving transdisciplinary research on culture and tobacco.

PMID- 14668091
TI  - Suppression of tumor necrosis factor-alpha-induced neutrophil adherence responses
      by essential oils.
AB  - BACKGROUND: In aromatherapy, essential oils are used as anti-inflammatory
      remedies, but experimental studies on their action mechanisms are very limited.
      AIMS: To assess their anti-inflammatory activities, effects of essential oils on
      neutrophil activation were examined in vitro. METHODS: Neutrophil activation was
      measured by tumor necrosis factor-alpha (TNF-alpha)-induced adherence reaction of
      human peripheral neutrophils. RESULTS: All essential oils tested at 0.1%
      concentration suppressed TNF-alpha-induced neutrophil adherence,and, in
      particular, lemongrass, geranium and spearmint oils clearly lowered the reaction
      even at 0.0125%. Similar inhibitory activities for the neutrophil adherence were
      obtained by their major constituent terpenoids: citral, geraniol, citronellol and
      carvone. In contrast, very popular essential oils, tea tree oil and lavender oil,
      did not display the inhibitory activity at the concentration. CONCLUSION: Thus,
      some essential oils used as antiinflammatory remedies suppress neutrophil
      activation by TNF-alpha at a low concentration (0.0125-0.025 %) in vitro.

PMID- 14668092
TI  - Dexamethasone-induced and estradiol-induced CREB activation and annexin 1
      expression in CCRF-CEM lymphoblastic cells: evidence for the involvement of cAMP
      and p38 MAPK.
AB  - AIMS: Annexin 1 (ANXA1), a member of the annexin family of calcium-binding and
      phospholipid-binding proteins, is a key mediator of the anti-inflammatory actions
      of steroid hormones. We have previously demonstrated that, in the human
      lymphoblastic CCRF-CEM cell line, both the synthetic glucocorticoid hormone,
      dexamethasone (Dex), and the estrogen hormone, 17beta-estradiol (E2beta), induce
      the synthesis of ANXA1, by a mechanism independent of the activation of their
      nuclear receptors. Recently, it was reported that the gene coding for ANXA1
      contains acAMP-responsive element (CRE). In this work, we investigated whether
      Dex and E2beta were able to induce the activation of CRE binding proteins (CREB)
      in the CCRF-CEM cells. Moreover, we studied the intracellular signalling pathways
      involved in CREB activation and ANXA1 synthesis in response to Dex and E2beta;
      namely, the role of cAMP and the p38 mitogen activated protein kinase (MAPK).
      RESULTS: The results show that Dex and E2beta were as effective as the cAMP
      analogue, dBcAMP, in inducing CREB activation. On the contrary, dBcAMP induced
      ANXA1 synthesis as effectively as these steroid hormones. Furthermore, the cAMP
      antagonist, Rp-8-Br-cAMPS, and the specific p38 MAPK inhibitor,SB203580,
      effectively prevented both Dex-induced, E2beta-induced and dBcAMP-induced CREB
      activation and ANXA1 synthesis. CONCLUSIONS: Taken together, our results suggest
      that,in CCRF-CEM cells, Dex-induced and E2beta-inducedANXA1 expression requires
      the activation of the transcription factor CREB, which in turn seems to be
      mediated by cAMP and the p38 MAPK. These findings also suggest that, besides the
      nuclear steroid hormone receptors, other transcription factors, namely CREB, may
      play important roles in mediating the anti-inflammatory actions of
      glucocorticoids and oestrogen hormones.

PMID- 14668093
TI  - Evaluation of caspase 1 and sFas serum levels in patients with systemic
      sclerosis: correlation with lung dysfunction, joint and bone involvement.
AB  - Recent studies point out at the role of apoptosis disturbances in the development
      of systemic sclerosis(SSc). The aim of our study was to examine caspase 1 and
      sFas serum levels in scleroderma patients and correlate the obtained results with
      skin involvement and internal organ changes. We studied 29 patients (14 with
      limited and 15 with diffuse SSc). The extension of skin involvement was measured
      using Total Skin Score (TSS). Internal organ involvement was assessed by
      specialist procedures. Serum caspase 1 and sFas levels were measured by enzyme
      linked immunosorbent assay. We found correlation between sFas serum level and
      duration of Raynaud's phenomenon and TSS; caspase 1 serum level correlated only
      with TSS. Correlations between caspase 1 and lung dysfunction and sFas levels
      with joint and bone involvement in SSc patients were also observed. The obtained
      results revealed that disturbances of apoptosis might play a role in SSc
      pathogenesis. Caspase 1 and sFas serum levels correlate with the skin involvement
      severity, lung dysfunction, joint and bone changes.

PMID- 14668094
TI  - Oxidative and adhesive responses of human neutrophils to nitrovasodilators in
      vitro: the role of protein kinases.
AB  - BACKGROUND: Sodium nitroprusside (SNP) and molsidomine are used in the treatment
      of coronary heart disease. Since the neutrophils play a pathological role in
      ischaemic heart disease, it is important to understand the direct action of
      nitrovasodilators on their function. AIM: We examined the effects of SNP and 3
      morpholinosydnonimine (SIN-1, molsidomine metabolite) on the respiratory burst of
      human neutrophils and their adhesion in vitro . The influence of nitric oxide
      (NO)donors on the activity of protein kinases, which are involved in the NADPH
      oxidase activation, was also investigated. METHODS: The respiratory burst of
      neutrophils was determined by chemiluminescence and fluorescence methods, while
      the adhesion was assayed by adherence of neutrophils to the plastic surface.
      RESULTS: NO donors decreased the oxidative burst of activated neutrophils.
      However, the effects of SNP and SIN-1 strongly depended on the treatment time of
      neutrophils and on the stimulus employed to cells activation. Protein kinase C
      inhibitor did not prevent the inhibitory effect of SIN-1, but diminished the
      inhibitory effect of SNP on the neutrophils' respiratory burst. Protein tyrosine
      kinase inhibitor did not affect the action of SNP, but diminished the inhibitory
      effect of SIN-1 on fMLP-stimulated but not on PMA stimulated oxidative burst of
      neutrophils. This suggests that SNP action is mainly associated with protein
      kinase C, while SIN-1 is associated with protein tyrosine kinase activity. We
      also found that SIN-1 but not SNP diminished the adhesive activity of
      neutrophils. CONCLUSIONS: Our data show that SIN-1 biological effect on some
      neutrophils activity is different from both spermine NONOate and SNP, and mainly
      depends on ONOO(-), while SNP action is mediated by NO.

PMID- 14668095
TI  - Role of soluble gp130 in the tumour necrosis factor-alpha expression and its
      production by peripheral blood mononuclear cells.
AB  - BACKGROUND: In our previous study we found that rhsIL-6R, along with recombinant
      human interleukin-6, plays a regulatory role in the immune response by modulating
      the tumour necrosis factor-alpha(TNF-alpha) expression and its production by
      peripheral blood mononuclear cells (PBMC). We also suggested that sIL-6R with IL
      6 secreted by human PMN (neutrophils) influenced the TNF-alpha expression and its
      production by autologous PBMC. AIMS: Since soluble gp130 (sgp130) is a natural
      inhibitor for sIL-6R/interleukin-6 responses, in the present study we estimated
      an effect of exogenous recombinant human sgp130 and sgp130 secreted by PMN on the
      TNF-alpha expression and its production by PBMC. METHODS: Cells were isolated
      from whole blood of healthy persons. The PMN were cultured in 96-well plates for
      1 h at 37 degrees C in a humidified incubator with 5% CO2. After the incubation,
      the culture supernatant of PMN was removed and added to the PBMC. PBMC were
      incubated for 1 h at 37 degrees C in the same conditions. Cytoplasmic protein
      fractions of PMN and, for comparative purpose of PBMC, were analysed for presence
      of sgp130 by western blotting with the use of monoclonal antibody capable of
      detecting this protein. In the culture supernatants of PMN we examined the
      concentrations of sgp130 by human enzyme-linked immunosorbent assay. TNF-alpha
      was measured at the protein levels as well as the mRNA levels. RESULTS AND
      CONCLUSIONS: The present results revealed that exogenous recombinant human
      sgp130modulates the TNF-alpha expression and production by PBMC. In contrast, we
      did not find any effect of sgp130 secreted by PMN on the TNF-alpha expression and
      its production by autologous PBMC.

PMID- 14668096
TI  - Levels of serum IL-1beta, IL-2, IL-8 and tumor necrosis factor-alpha in patients
      with unstable angina pectoris.
AB  - OBJECTIVES: Inflammation is the most important mechanism of plaque disruption
      playing an essential role in acute coronary syndromes. It is controversial
      whether the inflammatory mediators are the cause or the result in the development
      of plaque rupture. Stimulation of interleukins increases adhesion molecules,
      fibrinogen and plasminogen activator inhibitors,which cause the activation of
      inflammation and thrombosis. However, the importance of interleukins in acute
      coronary syndromes has not been clearly defined. We did not find any article
      concerning relations between the levels of serum interleukin(IL)-1beta, IL-2, IL 
      8 and tumor necrosis factor (TNF)-alpha in patients with unstable angina pectoris
      (UAP). So the aim of this study was to determine the levels of serum I -1b, IL-2,
      IL-8 and TNF-alpha during the early stage of UAP. METHODS AND RESULTS: Thirty
      seven patients with UAP(12 females and 25 males; mean age, 57.5 +/- 9.7 years)
      within 6 h of admission and 20 healthy volunteers(eight females and 12 males;
      mean age, 51.3 +/- 6.3 years) were included in the study. IL-1beta, IL-2, IL-8
      and TNF-alpha levels were measured using the enzyme-linked immunosorbent assay
      method. Patients with acute or chronic inflammation, renal failure or chronic
      heart failure were excluded from the study. The age, gender and risk factors of
      the study and control groups were similar. The levels of IL-1beta, IL-8 and TNF
      alpha were significantly increased (p < /0.0001, p < /0.001 and p < /0.016,
      respectively) in patients with UAP. There was no difference of IL-2 levels
      between the UAP group and controls. CONCLUSION: We detected high levels of IL
      1beta, IL-8 and TNF-alpha in patients with UAP during early phase. We suggest
      that proinflammatory cytokines (e.g. IL-1beta,IL-8, TNF-alpha) may play an
      important role in the development of atherosclerosis and its complications.

PMID- 14668098
TI  - Cases for change in mental health: partnership working in mental health services.
AB  - This article examines our current state of knowledge about partnership working
      between health and social care in UK adult mental health services. Drawing on a
      narrative review of the literature commissioned by the National Institute for
      Mental Health, this paper focuses on 43 documents from the review which discuss
      partnership issues. After exploring the rationale for partnership working,
      potential barriers and possible ways forward, the paper identifies gaps in the
      existing literature and discusses the implications of the review for current
      health and social care policy.

PMID- 14668099
TI  - The emergent role of the link worker: a study in collaboration.
AB  - Partnership working is integral to New Labour's approach to modernising health
      and social care services for vulnerable groups such as children with complex
      needs. This paper draws on an initiative from Cornwall and the Isles of Scilly in
      which strategic and operational change have been promoted across the health and
      social care community in order to provide co-ordinated assessment and care for
      children with complex needs and their families. The introduction of link workers
      has been central, key contacts for families and professionals alike who are drawn
      from a wide range of backgrounds. The political imperative for partnership,
      combined with the commitment and commonality of purpose of front-line staff, has
      proved sufficient to facilitate inter-professional working without many of the
      enabling factors that are often regarded as important, such as co-location or
      parity of status. However, a number of organisational barriers to sustainability
      remain and the degree to which a strong operational lead can secure the necessary
      breadth of strategic resource allocation and support remains questionable.

PMID- 14668100
TI  - How team working influences discharge planning from hospital: a study of four
      multi-disciplinary teams in an acute hospital in England.
AB  - A research project was carried out to critically explore and analyse what factors
      in an interdisciplinary/multidisciplinary context inhibited or promoted decision
      making for the discharge planning process for patients returning home from an
      acute hospital in London. This was done through observations, informal
      interviewing and focus groups held on two wards and with the supported discharge
      rehabilitation team. Data were analysed and a conceptual framework developed,
      highlighting the important factors namely: leadership, team working and
      communication, affected by behaviours, feelings and resources, including
      environmental as well as personnel resources. Further analysis of the data
      suggested that leadership, which acted as a nerve centre for pivoting
      information, orchestrating and representing the team, and ensuring good outcomes
      were all important for decision-making in discharge planning. Team working, based
      on sharing, agreeing responsibilities, roles and boundaries, developing trust,
      learning together were all important factors. The study showed that good team
      working and leadership are vital to the success of effective discharge planning,
      but these aspects are rarely investigated and few resources are targeted on
      improving them.

PMID- 14668101
TI  - Learning to work together: using the presage, process, product (3P) model to
      highlight decisions and possibilities.
AB  - Collaborative practice is seen as a core aspect of professional practice and,
      therefore, a focus of professional education. Current interprofessional and
      quality assurance literature provides enumeration and discussion of a range of
      competencies required for effective collaborative practice. Case studies of
      education and training related to collaborative competences rarely discuss the
      nature of influences on development, delivery and learning. Barriers to
      development and delivery have been identified for interprofessional education,
      but we want to move beyond the mental picture of climbing over or moving around
      fixed hurdles. Learning opportunities are complex dynamic systems, seeking
      equilibrium. The creative tension of influences provides opportunities for
      insightful management. This paper uses the systems-form 3P (presage-process
      product) model of learning and teaching (Biggs, 1993) to help examine the nature
      of educational opportunities designed to promote collaborative working. Presage,
      process and product factors are identified and discussed. We argue that
      untangling (or at least seeing) the web of influences on learning to work
      together promotes critical awareness and encourages more informed and timely
      decisions.

PMID- 14668102
TI  - Utilization of research methodology in designing and developing an
      interdisciplinary course in ethics.
AB  - Development research methodology was utilized to design an interdisciplinary
      ethics course for students from seven disciplines: dental hygiene, nursing, nurse
      anesthesia, occupational therapy, physician assistant, physical therapy, and
      social work. Two research questions, 'What content areas should be considered for
      inclusion in an interdisciplinary course in Ethics?' and 'What design framework,
      format, or structure would best fit the content chosen?' guided the study. An
      interdisciplinary faculty design team conducted a comparative analysis of each of
      the seven discipline's codes of ethics to find common topics of interest. Further
      analysis then grouped these topics into eight categories of professional
      responsibility. The result was a fifteen-week course with validated content
      relevant to all disciplines.

PMID- 14668103
TI  - Institutional collaboration and competition in community-based education.
AB  - We sought to determine whether competition for community-based training sites
      exists among health professions schools, and to examine faculty and senior
      administrators' perspectives on institutional collaboration for community-based
      education. Eight academic health centers (AHCs) in the USA were selected by
      objective criteria for their significant community involvement. Chief executive
      officers, vice chancellors, deans, and the individuals responsible for community
      based education, research and community service responded to written surveys. The
      overall response rate was 79% (n = 91). Responses were subjected to quantitative
      and qualitative analyses. Leaders of community-based education reported that
      "competition for community-based training sites" is a barrier to community
      involvement. "Competition for community-based training sites"was positively
      related to 'call for increasing percentage of graduates to enter primary care
      careers' (0.30, p < 0.01) and negative related to "collaboration exists between
      the community and your school/AHC" ( - 0.28, p < 0.05). Respondents reported that
      a moderate level of collaboration across schools exists. While medical school
      respondents reported having collaborative relationships with other health
      professions schools and with the community, nursing respondents reported
      medicine's performance at a significantly lower level. Public health and nursing
      faculty reported that they are competing with medical schools for sites they had
      traditionally used for their students. Competition for sites is an unintended
      outcome of the increased emphasis on community-based education in health
      professions curricula. We recommend AHCs form joint committees across schools to
      effectively address community-based sites as a limited resource, and to consider
      a wider range of community-based organizations as training partners.

PMID- 14668104
TI  - Primary health care teams: team members' perceptions of the collaborative
      process.

PMID- 14668105
TI  - Discharge planning and multidisciplinary teamwork: an interprofessional
      battlefield?

PMID- 14668109
TI  - Vehicle and mode of administration effects on the induction of aberrant crypt
      foci in the colons of male F344/N rats exposed to bromodichloromethane.
AB  - Bromodichloromethane (BDCM) and tribromomethane given by corn oil gavage were
      previously found to induce neoplasia in the large intestine of rats. Our chronic
      bioassay of BDCM administered in drinking water failed to produce colon neoplasia
      in male F344/N rats. We recently reported that BDCM induces aberrant crypt foci
      (ACF), putative precursor lesions in the development of colon cancer, when
      included in the drinking water of male rats. To investigate whether ACF induced
      by BDCM could be promoted by corn oil (CO), male F344/N rats were exposed to 0.7
      g BDCM/L in drinking water or 50 mg BDCM/kg body weight by oral gavage in CO.
      Animals exposed to drinking water, CO, or 15 mg/kg azoxymethane (AOM) (ip)
      constituted the negative, vehicle, and positive controls. After 26 wk, colons
      were examined for ACF. A significant decrease in water consumption was observed
      in both the positive controls and BDCM-treated animals; however, no difference
      was noted in final body weight. The administration of CO to AOM-exposed animals
      produced a significant increase in total ACF when compared to AOM alone. BDCM
      produced a significant increase in ACF when compared to control, but no
      difference was noticed between BDCM exposure by oral CO gavage and control.
      Additionally, no difference was noted between BDCM exposure by drinking water and
      by oral CO gavage. This study demonstrates that the formation of ACF is
      independent of the route of BDCM exposure (drinking water vs. oral corn oil
      gavage), with both routes producing similar ACF values of 1.33 +/- 0.49 and 1.5
      +/- 0.51 ACF/colon.

PMID- 14668108
TI  - Evidence of gender-and tissue-specific promoter methylation and the potential for
      ethinylestradiol-induced changes in Japanese medaka (Oryzias latipes) estrogen
      receptor and aromatase genes.
AB  - In order to explore the potential of DNA methylation to serve as a biomarker of
      toxicity, thus establishing a link between exposure to environmental contaminants
      and physiologically significant changes in gene expression, tissue- and gender
      specific methylation patterns in the promoter regions of estrogen receptor (ER)
      and aromatase genes of Japanese medaka (Oryzias latipes) were determined. Adult
      male and female medaka were exposed to either 0 or 500 ng/L 17 alpha
      ethinylestradiol (EE) for 14d via a waterborne exposure. Livers, gonads, and
      brains were removed and genomic DNA was extracted. Samples of genomic DNA were
      then analyzed by bisulfite-mediated methylation-specific polymerase chain
      reaction (PCR) of an approximately 300-bp region containing suspected methylation
      sites from the two genes, amplified, cloned, and sequenced. ER protein content in
      exposed medaka was significantly induced in all male and female tissues compared
      to controls. Aromatase activity in exposed medaka was significantly increased in
      the male brain, testes, and female brain as compared to controls. The methylation
      changes described by these studies indicate the potential for anthropogenic
      alteration of the mechanisms controlling gene expression, as well as gender- and
      tissue-specific sensitivity. While methylation differences were not paralleled by
      changes in protein expression in this study, changes in methylation have the
      potential to impact the regulation of normal gene expression and these changes
      could be transmitted to offspring.

PMID- 14668110
TI  - Assessment methods for concerns about contaminated sites.
AB  - The management and protection of environmental resources from anthropogenic
      stressors require public support. Understanding the concerns of the public with
      respect to environmental problems allows policymakers and managers to make wise
      decisions. In this study, three methods of assessing public concerns about
      Brookhaven National Laboratory, a Department of Energy facility on Long Island,
      NY, were compared using (1) an open-ended question about concerns, (2) a rating
      of a list of concerns, and (3) a ranking of the highest and lowest concern from a
      list provided. The greatest global and local concerns (as expressed as an open
      ended question) were pollution and environmental health, while the greatest
      concerns about Brookhaven National Laboratory (BNL) also included human health.
      Accidents, loss of public and ecological health, and nuclear material were rated
      the highest concerns on a rating scale. However, when asked to pick out the most
      important issue about BNL from a list, protecting human health and protecting
      ecology were the problems of most concern; protecting economic interests was
      rated the lowest. The three methods gave congruent results. No new concerns of
      major significance turned up on the open-ended question, suggesting that if a
      method is inclusive, a list of concerns can be given to stakeholders for
      quantitative analysis of public perceptions. Understanding of public concerns is
      critical to making sound management decisions, and this article contributes to
      our understanding of how to evaluate concerns about contaminated sites,
      particularly in urban areas.

PMID- 14668111
TI  - Physiologically based pharmacokinetic modeling of arsenic in the mouse.
AB  - A remarkable feature of the carcinogenicity of inorganic arsenic is that while
      human exposures to high concentrations of inorganic arsenic in drinking water are
      associated with increases in skin, lung, and bladder cancer, inorganic arsenic
      has not typically caused tumors in standard laboratory animal test protocols.
      Inorganic arsenic administered for periods of up to 2 yr to various strains of
      laboratory mice, including the Swiss CD-1, Swiss CR:NIH(S), C57Bl/6p53(+/-), and
      C57Bl/6p53(+/+), has not resulted in significant increases in tumor incidence.
      However, Ng et al. (1999) have reported a 40% tumor incidence in C57Bl/6J mice
      exposed to arsenic in their drinking water throughout their lifetime, with no
      tumors reported in controls. In order to investigate the potential role of tissue
      dosimetry in differential susceptibility to arsenic carcinogenicity, a
      physiologically based pharmacokinetic (PBPK) model for inorganic arsenic in the
      rat, hamster, monkey, and human (Mann et al., 1996a, 1996b) was extended to
      describe the kinetics in the mouse. The PBPK model was parameterized in the mouse
      using published data from acute exposures of B6C3F1 mice to arsenate, arsenite,
      monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) and validated using
      data from acute exposures of C57Black mice. Predictions of the acute model were
      then compared with data from chronic exposures. There was no evidence of changes
      in the apparent volume of distribution or in the tissue-plasma concentration
      ratios between acute and chronic exposure that might support the possibility of
      inducible arsenite efflux. The PBPK model was also used to project tissue
      dosimetry in the C57Bl/6J study, in comparison with tissue levels in studies
      having shorter duration but higher arsenic treatment concentrations. The model
      evaluation indicates that pharmacokinetic factors do not provide an explanation
      for the difference in outcomes across the various mouse bioassays. Other possible
      explanations may relate to strain-specific differences, or to the different
      durations of dosing in each of the mouse studies, given the evidence that
      inorganic arsenic is likely to be active in the later stages of the carcinogenic
      process.

PMID- 14668112
TI  - Ultraviolet radiation downregulates allergy in BALB/c mice.
AB  - The immunosuppressive effects of exposure to ultraviolet radiation (UVR) are well
      known and the underlying mechanisms extensively studied. The suppression of Th1
      appears to account for UVR suppression of contact hypersensitivity and delayed
      type hypersensitivity responses and increased susceptibility to certain
      infections and tumor development. The underlying mechanisms suggest Th2-mediated
      responses associated with immediate-type hypersensitivity and allergic lung
      disease should be unchanged or possibly enhanced by UVR. The hypothesis that UVR
      exposure enhances allergic lung disease in BALB/c mice was tested. Effects of UVR
      on sensitization and elicitation of respiratory hypersensitivity were assessed
      using a fungal extract, Metarhizium anisopliae (MACA), as the allergen. BALB/c
      mice were sham or UVR (8 KJ/m(2)) exposed 3d before involuntary aspiration (IA)
      of MACA or vehicle. The mice received UVR exposures before the first and second
      of three IAs in the sensitization protocol and 3 d before the fourth IA in the
      elicitation protocol. Serum and bronchoalveolar lavage fluid (BALF) were
      harvested before (d 21, sensitization/d 24, elicitation) and at 1 (d 22/d 28), 3
      (d 24/d 29), and 7 (d 28/d 35) d following the last IA. UVR exposure prior to
      sensitization suppressed two hallmarks of allergic disease, immune-mediated
      inflammation (eosinophil influx) and total immunoglobulin (Ig)E compared to the
      sham-UVR controls. There were no differences attributable to UVR exposure in
      previously sensitized mice. These data suggest that UVR exposure prior to
      sensitization suppresses allergic responses but has no effect on the elicitation
      of allergic responses in previously sensitized individuals. Consequently, there
      is no evidence that exposure to UVR enhances the induction or expression of
      allergic lung disease.

PMID- 14668113
TI  - Exposure to carbon nanotube material: aerosol release during the handling of
      unrefined single-walled carbon nanotube material.
AB  - Carbon nanotubes represent a relatively recently discovered allotrope of carbon
      that exhibits unique properties. While commercial interest in the material is
      leading to the development of mass production and handling facilities, little is
      known of the risk associated with exposure. In a two-part study, preliminary
      investigations have been carried out into the potential exposure routes and
      toxicity of single-walled carbon nanotube material (SWCNT)--a specific form of
      the allotrope. The material is characterized by bundles of fibrous carbon
      molecules that may be a few nanometers in diameter, but micrometers in length.
      The two production processes investigated use-transition metal catalysts, leading
      to the inclusion of nanometer-scale metallic particles within unrefined SWCNT
      material. A laboratory-based study was undertaken to evaluate the physical nature
      of the aerosol formed from SWCNT during mechanical agitation. This was
      complemented by a field study in which airborne and dermal exposure to SWCNT was
      investigated while handling unrefined material. Although laboratory studies
      indicated that with sufficient agitation, unrefined SWCNT material can release
      fine particles into the air, concentrations generated while handling material in
      the field were very low. Estimates of the airborne concentration of nanotube
      material generated during handling suggest that concentrations were lower than 53
      microg/m(3) in all cases. Glove deposits of SWCNT during handling were estimated
      at between 0.2 mg and 6 mg per hand.

PMID- 14668114
TI  - Phylogenetic systematics and evolution of primate-derived Pneumocystis based on
      mitochondrial or nuclear DNA sequence comparison.
AB  - Previous studies have demonstrated that the agent of Pneumocystis pneumonia
      (PcP), Pneumocystis carinii, is actually a complex of eukaryotic organisms, and
      cophylogeny could explain the distribution of the hosts and parasites. In the
      present work, we tested the hypothesis of cophylogeny between the primate-derived
      Pneumocystis group and their hosts. Specific strains isolated from 20 primate
      species, including humans, were used to produce a phylogeny of the parasites.
      Aligned sequences corresponding to DNA sequences of three genes (DHPS, mtSSU
      rRNA, and mtLSU-rRNA) were separately analyzed and then combined in a single data
      set. The resulting parasite phylogeny was compared with different controversial
      phylogenies for the hosts. This comparison demonstrated that, depending upon
      which topology is accepted for the hosts, at least 61% and perhaps 77% of the
      homologous nodes of the respective cladograms of the hosts and parasites may be
      interpreted as resulting from codivergence events. This finding and the high
      specificity of these parasites suggests that cophylogeny may be considered the
      dominant pattern of evolution for Pneumocystis organisms, representing a new
      example of parallel evolution between primates and their specific parasites.
      Because the phylogeny of Pneumocystis followed very closely the differentiation
      of their hosts at the species level, the study of the parasites could provide
      valuable information on the phylogeny of their hosts. We used this information to
      explore controversial hypotheses of the phylogeny of the Platyrrhini by
      comparison with the phylogeny of their specific Pneumocystis parasites. If these
      organisms were closely associated as lung parasites with primates through the
      ages, the hypothesis of the Pneumocystis spp. being new pathogenic agents could
      be refuted. However, these organisms are opportunistic symbionts, becoming
      pathogenic whenever the immunological defences of their hosts decline. This study
      also provides support for the hypothesis that the different Pneumocystis species
      are genetically independent organisms, helping to clarify their taxonomic status.

PMID- 14668115
TI  - Time flies, a new molecular time-scale for brachyceran fly evolution without a
      clock.
AB  - The insect order Diptera, the true flies, contains one of the four largest
      Mesozoic insect radiations within its suborder Brachycera. Estimates of
      phylogenetic relationships and divergence dates among the major brachyceran
      lineages have been problematic or vague because of a lack of consistent evidence
      and the rarity of well-preserved fossils. Here, we combine new evidence from
      nucleotide sequence data, morphological reinterpretations, and fossils to improve
      estimates of brachyceran evolutionary relationships and ages. The 28S ribosomal
      DNA (rDNA) gene was sequenced for a broad diversity of taxa, and the data were
      combined with recently published morphological scorings for a parsimony-based
      phylogenetic analysis. The phylogenetic topology inferred from the combined 28S
      rDNA and morphology data set supports brachyceran monophyly and the monophyly of
      the four major brachyceran infraorders and suggests relationships largely
      consistent with previous classifications. Weak support was found for a basal
      brachyceran clade comprising the infraorders Stratiomyomorpha (soldier flies and
      relatives), Xylophagomorpha (xylophagid flies), and Tabanomorpha (horse flies,
      snipe flies, and relatives). This topology and similar alternative arrangements
      were used to obtain Bayesian estimates of divergence times, both with and without
      the assumption of a constant evolutionary rate. The estimated times were
      relatively robust to the choice of prior distributions. Divergence times based on
      the 28S rDNA and several fossil constraints indicate that the Brachycera
      originated in the late Triassic or earliest Mesozoic and that all major lower
      brachyceran fly lineages had near contemporaneous origins in the mid-Jurassic
      prior to the origin of flowering plants (angiosperms). This study provides
      increased resolution of brachyceran phylogeny, and our revised estimates of fly
      ages should improve the temporal context of evolutionary inferences and genomic
      comparisons between fly model organisms.

PMID- 14668116
TI  - Systematics of the lizard family pygopodidae with implications for the
      diversification of Australian temperate biotas.
AB  - We conducted a phylogenetic study of pygopodid lizards, a group of 38 species
      endemic to Australia and New Guinea, with two major goals: to reconstruct a
      taxonomically complete and robustly supported phylogeny for the group and to use
      this information to gain insights into the tempo, mode, and timing of the
      pygopodid radiation. Phylogenetic analyses of mitochondrial DNA (mtDNA), nuclear
      DNA (nDNA), and previously published morphological data using parsimony, maximum
      likelihood, and Bayesian methods on the independent and combined three data sets
      yielded trees with similar and largely stable ingroup topologies. However,
      relationships among the six most inclusive and unambiguously supported clades
      (Aprasia, Delma, Lialis, Ophidiocephalus, Pletholax, and Pygopus) varied
      depending on data set analyzed. We used parametric bootstrapping to help us
      understand which of the three-branch schemes linking these six taxa was most
      plausible given our data. We conclude based on our results that the arrangement
      ((((Delma, Lialis)Pygopus)Pletholax)(Aprasia, Ophidiocephalus)) represents the
      best hypothesis of intergeneric relationships. A second major problem to arise in
      our study concerned the inability of our two outgroup taxa (Diplodactylus) to
      root trees properly; three different rooting locations were suggested depending
      upon analysis. This long-branch attraction problem was so severe that the
      outgroup branch also interfered with estimation of ingroup relationships. We
      therefore used the molecular clock method to root the pygopodid tree. Results of
      two independent molecular clock analyses (mtDNA and nDNA) converged upon the same
      root location (branch leading to Delma). We are confident that we have found the
      correct root because the possibility of our clock estimates agreeing by chance
      alone is remote given that there are 65 possible root locations (branches) on the
      pygopodid tree (approximately 1 in 65 odds). Our analysis also indicated that
      Delma fraseri is not monophyletic, a result supported by a parametric
      bootstrapping test. We elevated the Western Australian race, Delma f. petersoni,
      to species status (i.e., Delma petersoni) because hybridization and incomplete
      lineage sorting could be ruled out as potential causes of this paraphyletic gene
      tree and because D. grayii is broadly sympatric with its sister species D.
      fraseri. Climate changes over the past 23 million years, which transformed
      Australia from a wet, green continent to one that is largely dry and brown, have
      been suspected as playing a major role in the diversification of Australia's
      temperate biotas. Our phylogenetic analyses of pygopodid speciation and
      biogeography revealed four important findings consistent with this climate change
      diversification model: (1) our fossil-calibrated phylogeny shows that although
      some extant pygopodid lineages predate the onset of aridification, 28 of 33
      pygopodid species included in our study seem to have originated in the last 23
      million years; (2) relative cladogenesis tests suggest that several major clades
      underwent higher than expected rates of speciation; (3) our findings support
      earlier studies showing that speciation of mesic-adapted biotas in the
      southeastern and southwestern corners of Australia largely occurred within each
      of these regions between 12 and 23 million years ago as opposed to repeated
      dispersal between these regions; and (4) we have identified for the first time
      the existence of several pairs of sympatric sister species of lizards living in
      arid and semiarid ecosystems. These sympatric sister species seem to be younger
      than allopatric or parapatric sister-species pairs, which is not consistent with
      previous beliefs.

PMID- 14668117
TI  - Least and most powerful phylogenetic tests to elucidate the origin of the seed
      plants in the presence of conflicting signals under misspecified models.
AB  - Several tests of molecular phylogenies have been proposed over the last decades,
      but most of them lead to strikingly different P-values. I propose that such
      discrepancies are principally due to different forms of null hypotheses. To
      support this hypothesis, two new tests are described. Both consider the composite
      null hypothesis that all the topologies are equidistant from the true but unknown
      topology. This composite hypothesis can either be reduced to the simple
      hypothesis at the least favorable distribution (frequentist significance test
      [FST]) or to the maximum likelihood topology (frequentist hypothesis test [FHT]).
      In both cases, the reduced null hypothesis is tested against each topology
      included in the analysis. The tests proposed have an information-theoretic
      justification, and the distribution of their test statistic is estimated by a
      nonparametric bootstrap, adjusting P-values for multiple comparisons. I applied
      the new tests to the reanalysis of two chloroplast genes, psaA and psbB, and
      compared the results with those of previously described tests. As expected, the
      FST and the FHT behaved approximately like the Shimodaira-Hasegawa test and the
      bootstrap, respectively. Although the tests give overconfidence in a wrong tree
      when an overly simple nucleotide substitution model is assumed, more complex
      models incorporating heterogeneity among codon positions resolve some conflicts.
      To further investigate the influence of the null hypothesis, a power study was
      conducted. Simulations showed that FST and the Shimodaira-Hasegawa test are the
      least powerful and FHT is the most powerful across the parameter space. Although
      the size of all the tests is affected by misspecification, the two new tests
      appear more robust against misspecification of the model of evolution and
      consistently supported the hypothesis that the Gnetales are nested within
      gymnosperms.

PMID- 14668118
TI  - Phylogenetics of fanged frogs: testing biogeographical hypotheses at the
      interface of the asian and Australian faunal zones.
AB  - The interface of the Asian and Australian faunal zones is defined by a network of
      deep ocean trenches that separate intervening islands of the Philippines and
      Wallacea (Sulawesi, the Lesser Sundas, and the Moluccas). Studies of this region
      by Wallace marked the genesis of the field of biogeography, yet few workers have
      used molecular methods to investigate the biogeography of taxa whose distribution
      spans this interface. Some taxa, such as the fanged frogs of the ranid genus
      Limnonectes, have distributions on either side of the zoogeographical lines of
      Wallace and Huxley, offering an opportunity to ask how frequently these purported
      barriers were crossed and by what paths. To examine diversification of
      Limnonectes in Southeast Asia, the Philippines, and Wallacea, we estimated a
      phylogeny from mitochondrial DNA sequences obtained from a robust geographic
      sample. Our analyses suggest that these frogs dispersed from Borneo to the
      Philippines at least twice, from Borneo to Sulawesi once or twice, from Sulawesi
      to the Philippines once, and from the Philippines to Sulawesi once. Dispersal to
      the Moluccas occurred from Sulawesi and to the Lesser Sundas from Java/Bali.
      Species distributions are generally concordant with Pleistocene aggregate island
      complexes of the Philippines and with areas of endemism on Sulawesi. We conclude
      that the recognition of zoogeographic lines, though insightful, may oversimplify
      the biogeography of widespread taxa in this region.

PMID- 14668119
TI  - Reconstructing ancestral patterns of colonization and dispersal in the Hawaiian
      understory tree genus Psychotria (Rubiaceae): a comparison of parsimony and
      likelihood approaches.
AB  - Systematic and biogeographical relationships within the Hawaiian clade of the
      pantropical understory shrub genus Psychotria (Rubiaceae) were investigated using
      phylogenetic analysis of 18S-26S ribosomal DNA internal (ITS) and external (ETS)
      transcribed spacers. Phylogenetic analyses strongly suggest that the Hawaiian
      Psychotria are monophyletic and the result of a single introduction to the
      Hawaiian Islands. The results of phylogenetic analyses of ITS and ETS partitions
      alone give slightly different topologies among basal lineages of the Hawaiian
      clade; however, such differences are not well supported. Relationships in the
      section Straussia clade in particular are not well resolved because of few
      nucleotide changes on internal branches, suggesting extremely rapid radiation in
      the lineage. Parsimony and likelihood reconstructions of ancestral geographical
      distributions using the topologies inferred from both parsimony and likelihood
      analysis of combined data and using different combinations of models and branch
      lengths gave highly congruent results. However, for one internal node
      (corresponding to the majority of the "greenwelliae" clade), parsimony
      reconstructions were unable to distinguish between three possible island states,
      whereas likelihood reconstructions resulted in clear ordering of possible states,
      with the island of Oahu slightly more probable than other islands under all but
      one model and branch length combination considered (the Jukes-Cantor-like model
      with branch lengths inferred under parsimony, under which conditions Maui Nui is
      more probable). A pattern of colonization from oldest to youngest islands was
      inferred from the phylogeny, using maximum parsimony and maximum likelihood.
      Additionally, a much higher incidence of intraisland versus interisland
      speciation was inferred.

PMID- 14668120
TI  - Novel versus unsupported clades: assessing the qualitative support for clades in
      MRP supertrees.
AB  - Matrix representation with parsimony (MRP) supertree construction has been
      criticized because the supertree may specify clades that are contradicted by
      every source tree contributing to it. Such unsupported clades may also occur
      using other supertree methods; however, their incidence is largely unknown. In
      this study, I investigated the frequency of unsupported clades in both simulated
      and empirical MRP supertrees. Here, I propose a new index, QS, to quantify the
      qualitative support for a supertree and its clades among the set of source trees.
      Results show that unsupported clades are very rare in MRP supertrees, occurring
      most often when there are few source trees that all possess the same set of taxa.
      However, even under these conditions the frequency of unsupported clades was
      <0.2%. Unsupported clades were absent from both the Carnivora and Lagomorpha
      supertrees, reflecting the use of large numbers of source trees for both. The
      proposed QS indices are correlated broadly with another measure of quantitative
      clade support (bootstrap frequencies, as derived from resampling of the MRP
      matrix) but appear to be more sensitive. More importantly, they sample at the
      level of the source trees and thus, unlike the bootstrap, are suitable for
      summarizing the support of MRP supertree clades.

PMID- 14668121
TI  - Branch lengths and support: revisited.

PMID- 14668122
TI  - Phylogenetic methods and aetosaur interrelationships: a rejoinder.

PMID- 14668123
TI  - Are the dental data really at odds with the molecular data? Morphological
      evidence for whale phylogeny (re)reexamined.

PMID- 14668125
TI  - Matrix representations with parsimony or with distances: two sides of the same
      coin?

PMID- 14668128
TI  - From data to knowledge in e-health applications: an integrated system for medical
      information modelling and retrieval.
AB  - The system described in this paper uses the technological advances in information
      technology in order to influence and improve healthcare practice by enabling the
      flexible modelling, direct representation and adaptable use of medical knowledge.
      It aims at resolving a number of difficulties encountered by current information
      repositories, such as costly customization, reusability, high maintenance and
      poor information modelling, by employing the architecture of the functional data
      model (FDM), while maintaining full interoperability with existing systems by
      means of XML. On the information-modelling front the system supports a variety of
      modelling techniques that are especially relevant to medical applications, such
      as complex objects, incomplete or missing information, partially structured data
      and multimedia content. A prototype implementation of the system has been
      developed which consists of a multimedia-enhanced version of the functional
      database language FDL, and a web-based, two-way translator interface between the
      application's native language and XML. This interface provides full
      interoperability with other, heterogeneous systems over the web, thus,
      significantly reducing the complexity of developing distributed healthcare
      systems and e-health applications.

PMID- 14668129
TI  - Security issues in the electronic transmission of prescriptions.
AB  - The UK government has stated within its plan of reform for the National Health
      Service that a secure system for the Electronic Transfer of Prescriptions will be
      available by 2004. The objectives of this paper are to highlight the significant
      barriers faced in securing an ETP system, to provide a critical analysis of the
      security mechanisms in the models currently being piloted and to suggest an
      alternative revised model which overcomes the identified deficiencies and
      security hurdles. To identify the significant security issues relevant to the
      adoption of ETP, the authors have combined their analysis of present prescription
      processing practice with their knowledge of computer security. The authors
      identify and describe how the issues of patient confidentiality, authorization,
      identity authentication, audit, scalability, availability and reliability are
      significant barriers to the adoption of ETP, particularly if they effect ease of
      use. The paper's contribution to the field of ETP is to suggest solutions to each
      of the identified security issues and to combine the solutions together in a
      revised and developed model.

PMID- 14668130
TI  - Identifying exposures of in vitro fertilization from drug reimbursement files: a
      case study from Finland.
AB  - OBJECTIVE: This article describes an innovative method to identify infertility
      interventions from drug reimbursement data, which did not contain diagnoses.
      METHODS: An algorithm of usual infertility care steps was designed and
      information on drug prescriptions were retrieved from the Drug Reimbursement
      Register and linked to a register covering examinations and interventions in
      private health care. The data were compared to in vitro fertilization (IVF)
      statistics and the Birth Register. RESULTS: Despite the novelty of the idea, the
      complexity of the pharmacological details, the use of administrative registers
      not commonly used for research, and the involvement of two institutions, the
      identification of the exposed cohorts went well. An estimated 16 work-weeks were
      used. The numbers of started IVF-cycles with fresh embryos were similar to those
      in statistics, but our data had more transfers of frozen embryos. The linkage to
      the Birth Register gave further support that our algorithm worked well.
      Classification into different IVF-classes was not accurate. CONCLUSION: Even
      though diagnoses were not recorded in the Finnish drug reimbursement data, the
      algorithm approach allowed exposure identification.

PMID- 14668131
TI  - Development of Web-based intervention system for periodontal health: a pilot
      study in the workplace.
AB  - BACKGROUND: It has recently been accepted that periodontal disease is a risk
      factor for not only tooth loss but also systemic diseases. An effective system of
      public intervention for periodontal health to enable continuous intervention of
      dental professionals has been sought. We developed a Web-based intervention
      system regarding periodontal health and evaluated the effects of the system in
      the workplace. METHODS: The system was capable of storage and display of
      personalized oral health records including video images pertaining to toothbrush
      manipulation within their own oral cavities based on instructions by dental
      professionals. The system enabled clients to view movement of their own skill,
      and repeatedly. Thirteen workers of a company were randomized to either an
      experimental or control group. The control group received face-to-face
      toothbrushing instruction at the company and follow-up via telephone. The
      experimental group received follow-up through our system in addition to those
      components employed in the control group. MAIN RESULTS: The workers in the
      experimental group benefited in terms of improvements of not only plaque removal
      but also periodontal health over 3 months. CONCLUSIONS: These results indicate
      that implementation of an Web-based approach for periodontal health affords the
      possibility of remote instruction and produces additional public benefit.

PMID- 14668132
TI  - Neural networks for the prediction of spirometric reference values.
AB  - Normal lung function values are conventionally calculated according to prediction
      equations. The primary objective of this study is the development of a different
      method for the prediction of FVC and FEV1 parameters, in order to achieve better
      correlation of the predicted values to the real ones. Using a sample from the
      Greek elderly population that was separated into two groups (a training and a
      testing one), a number of artificial neural networks were trained. Considering
      that men and women were studied separately and that two parameters (FVC, FEV1)
      were the target of the study, four cases came up. In each case two neural
      networks were trained using different transfer functions, number of neurons and
      number of layers. When passing the inputs of the testing data set to the trained
      networks it was found that the outputs were well correlated with the
      corresponding measures of the sample. Furthermore, the match with the sample, for
      a number of neural networks developed, was better compared to the matches of
      Baltopoulos et al. study that used the same sample for developing prediction
      equations. This high match allows the potential use of neural networks for
      predicting not only FVC and FEV1 but also other spirometric parameters.

PMID- 14668133
TI  - Transport of physiological nucleosides and anti-viral and anti-neoplastic
      nucleoside drugs by recombinant Escherichia coli nucleoside-H(+) cotransporter
      (NupC) produced in Xenopus laevis oocytes.
AB  - The recently identified human and rodent plasma membrane proteins CNT1, CNT2 and
      CNT3 belong to a gene family (CNT) that also includes the bacterial nucleoside
      transport protein NupC. Heterologous expression in Xenopus oocytes has
      established that CNT1-3 correspond functionally to the three major concentrative
      nucleoside transport processes found in human and other mammalian cells (systems
      cit, cif and cib, respectively) and mediate Na(+) - linked uptake of both
      physiological nucleosides and anti-viral and anti-neoplastic nucleoside drugs.
      Here, one describes a complementary Xenopus oocyte transport study of Escherichia
      coli NupC using the plasmid vector pGEM-HE in which the coding region of NupC was
      flanked by 5'- and 3'-untranslated sequences from a Xenopus beta-globin gene.
      Recombinant NupC resembled human (h) and rat (r) CNT1 in nucleoside selectivity,
      including an ability to transport adenosine and the chemotherapeutic drugs 3'
      azido-3'-deoxythymidine (AZT), 2',3'- dideoxycytidine (ddC) and 2'-deoxy-2',2'
      difluorocytidine (gemcitabine), but also interacted with inosine and 2',3'-
      dideoxyinosine (ddl). Apparent affinities were higher than for hCNT1, with
      apparent K(m) values of 1.5-6.3 microM for adenosine, uridine and gemcitabine,
      and 112 and 130 microM, respectively, for AZT and ddC. Unlike the relatively low
      translocation capacity of hCNT1 and rCNT1 for adenosine, NupC exhibited broadly
      similar apparent V(max) values for adenosine, uridine and nucleoside drugs. NupC
      did not require Na(+) for activity and was H(+) - dependent. The kinetics of
      uridine transport measured as a function of external pH were consistent with an
      ordered transport model in which H(+) binds to the transporter first followed by
      the nucleoside. These experiments establish the NupC-pGEM-HE/oocyte system as a
      useful tool for characterization of NupC-mediated transport of physiological
      nucleosides and clinically relevant nucleoside therapeutic drugs.

PMID- 14668134
TI  - Functional expression and characterization of a purine nucleobase transporter
      gene from Leishmania major.
AB  - Leishmania major, like all the other kinetoplastid protozoa, are unable to
      synthesize purines and rely on purine nucleobase and nucleoside acquisition
      across the parasite plasma membrane by specific permeases. Although, several
      genes have been cloned that encode nucleoside transporters in Leishmania and
      Trypanosoma brucei, much less progress has been made on nucleobase transporters,
      especially at the molecular level. The studies reported here have cloned and
      expressed the first gene for a L. major nucleobase transporter, designated
      LmaNT3. The LmaNT3 permease shows 33% identity to L. donovani nucleoside
      transporter 1.1 (LdNT1.1) and is, thus, a member of the equilibrative nucleoside
      transporter (ENT) family. ENT family members identified to date are nucleoside
      transporters, some of which also transport one or several nucleobases. Functional
      expression studies in Xenopus laevis oocytes revealed that LmaNT3 mediates high
      levels of uptake of hypoxanthine, xanthine, adenine and guanine. Moreover, LmaNT3
      is an high affinity transporter with K(m) values for hypoxanthine, xanthine,
      adenine and guanine of 16.5 +/- 1.5, 8.5 +/- 0.6, 8.5 +/- 1.1, and 8.8 +/- 4.0
      microM, respectively. LmaNT3 is, thus, the first member of the ENT family
      identified in any organism that functions as a nucleobase rather than nucleoside
      or nucleoside/nucleobase transporter.

PMID- 14668135
TI  - Differential modulation of Kv1 channel-mediated currents by co-expression of
      Kvbeta3 subunit in a mammalian cell-line.
AB  - The effect of Kvbeta3 subunit co-expression on currents mediated by the Shaker
      related channels Kv1.1 to Kv1.6 in Chinese hamster ovary (CHO) cells was studied
      with patch-clamp techniques. In the presence of Kvbeta3, differences in the
      voltage dependence of activation for Kv1.1, Kv1.3 and Kv1.6 were detected, but
      not for Kv1.2- and Kv1.4-mediated currents. Co-expression of Kvbeta3 did not
      cause a significant increase in current density for any of the tested channels.
      In contrast to previous studies in Xenopus oocyte expression system, Kvbeta3
      confered a rapid inactivation to all except Kv1.3 channels. Also, Kv1.6 channels
      that possess an N-type inactivation prevention (NIP) domain for Kvbeta1.1,
      inactivated rapidly when co-expressed with Kvbeta3. Onset and recovery kinetics
      of channel inactivation distinctly differed for the various Kv1alpha/Kvbeta3
      subunit combinations investigated in this study. The results indicate that the
      choice of expression system may critically determine Kvbeta3 inactivating
      activity. This suggests that the presence of an inactivating domain and a
      receptor in a channel pore, although necessary, may not be sufficient for an
      effective rapid N-type inactivation of Kv1 channels in heterologous expression
      systems.

PMID- 14668136
TI  - Direct block of the cystic fibrosis transmembrane conductance regulator Cl(-)
      channel by niflumic acid.
AB  - Niflumic acid is widely used to inhibit Ca(2+) -activated Cl(-) channels.
      However, the chemical structure of niflumic acid resembles that of diphenylamine
      2-carboxylate, a drug that inhibits the cystic fibrosis transmembrane conductance
      regulator (CFTR) Cl(-) channel. To investigate how niflumic acid inhibits CFTR
      Cl(-) channel, we studied recombinant wild-type human CFTR in excised inside-out
      membrane patches. When added to the intracellular solution, niflumic acid caused
      a concentration- and voltage-dependent decrease of CFTR Cl(-) current with half
      maximal inhibitory concentration (K(i)) of 253 microM and Hill co-efficient of
      approximately 1, at -50 mV. Niflumic acid inhibition of single CFTR Cl(-)
      channels was characterized by a very fast, flickery block that decreased
      dramatically current amplitude without altering open-probability. Consistent with
      these data, spectral analysis of CFTR Cl(-) currents suggested that channel block
      by niflumic acid was described by the closed <--> open <--> blocked kinetic
      scheme with blocker on rate (k(on)) = 13.9 x 10(6) M(-1)s(-1), off rate
      (k(off))=3348 s(-1) and dissociation constant (K(d)) = 241 microM, at -50 mV.
      Based on these data, we tested the effects of niflumic acid on transepithelial
      Cl(-) secretion and cyst growth using type I MDCK epithelial cells. Niflumic acid
      (200 microM) inhibited cAMP-stimulated, bumetanide-sensitive short-circuit
      current by 55%. Moreover, the drug potently retarded cyst growth. We conclude
      that niflumic acid is an open-channel blocker of CFTR that inhibits Cl(-)
      permeation by plugging the channel pore. It or related agents might be of value
      in the development of new therapies for autosomal dominant polycystic kidney
      disease.

PMID- 14668137
TI  - Mechanistic contributions of residues in the M1 transmembrane domain of the
      nicotinic receptor to channel gating.
AB  - The nicotinic receptor (AChR) is a pentamer of homologous subunits with an
      alpha(2)betaepsilondelta composition in adult muscle. Each subunit contains four
      transmembrane domains (M1-M4). Position 15' of the M1 domain is phenylalanine in
      alpha subunits while it is isoleucine in non-alpha subunits. Given this peculiar
      conservation pattern, we studied its contribution to muscle AChR activation by
      combining mutagenesis with single-channel kinetic analysis. AChRs containing the
      mutant alpha subunit (alphaF15'I) as well as those containing the reverse
      mutations in the non-alpha subunits (betaI15'F, deltaI15'F, and epsilonI15'F)
      show prolonged lifetimes of the diliganded open channel resulting from a slower
      closing rate with respect to wild-type AChRs. The kinetic changes are not
      equivalent among subunits, the beta subunit, being the one that produces the most
      significant stabilization of the open state. Kinetic analysis of betaI15'F of
      AChR channels activated by the low-efficacious agonist choline revealed a 10-fold
      decrease in the closing rate, a 2.5-fold increase in the opening rate, a 28-fold
      increase in the gating equilibrium constant in the diliganded receptor, and a
      significant increase opening in the absence of agonist. Mutations at betaI15'
      showed that the structural bases of its contribution to gating is complex. Rate
      equilibrium linear free-energy relationships suggest an approximately 70% closed
      state-like environment for the beta15' position at the transition state of
      gating. The overall results identify position 15' as a subunit-selective
      determinant of channel gating and add new experimental evidence that gives
      support to the involvement of the M1 domain in the operation of the channel
      gating apparatus.

PMID- 14668138
TI  - Functional characterization of the Escherichia coli K-12 yiaMNO transport protein
      genes.
AB  - The yiaMNO genes of Escherichia coli K-12 encode a binding protein-dependent
      secondary, or tri-partite ATP-independent periplasmic (TRAP), transporter. Since
      only a few members of this family have been functionally characterized to date,
      we aimed to identify the substrate for this transporter. Cells that
      constitutively express the yiaK-S gene cluster metabolized the rare pentose L
      xylulose, while deletion of the yiaMNO transporter genes reduced L-xylulose
      metabolism. The periplasmic substrate-binding protein YiaO was found to bind L
      xylulose, and stimulated L-xylulose uptake by spheroplasts. These date indicate
      that the yiaMNO transporter mediates uptake of this rare pentose.

PMID- 14668139
TI  - Actin and microtubule regulation of trans-Golgi network architecture, and copper
      dependent protein transport to the cell surface.
AB  - The Menkes disease ATPase (MNK) is a copper transporter that localizes to the
      mammalian trans-Golgi network (TGN) and shows substantial co-localization wih a
      ubiquitous TGN resident protein and marker, TGN46. We tested our hypothesis that
      these two TGN residents and integral membrane proteins are localized to
      biochemically distinct TGN sub-compartments using constitutively active mutant
      proteins and drugs that disrupt membrane traffic, lumenal pH and the cellular
      cytoskeleton. The pH-disrupting agent, monensin, causes MNK to be more diffusely
      distributed with partial separation of staining patterns for these two TGN
      residents. Expression of a constitutively active Rho-kinase (ROCK-KIN), which
      causes formation of juxta-nuclear astral actin arrays, also effects separation of
      MNK and TGN46 staining patterns. Treatment of ROCK-KIN expressing cells with
      latrunculin B, an actin-depolymerizing agent, causes complete overlap of MNK and
      TGN46 staining patterns with concomitant disappearance of polymerized actin. When
      microtubules are depolymerized in ROCK-KIN expressing cells by nocodazole, both
      MNK and TGN46 are found in puncate structures throughout the cell. However, a
      substantial proportion of MNK is still found in a juxta-nuclear location in
      contrast to TGN46. Actin distribution in these cells reveals that juxta-nuclear
      MNK is distinct to the astral actin clusters in ROCK-KIN expressing cells where
      the microtubules were depolymerized. The TGN to cell-surface transport of MNK
      requires both actin and microtubules networks, whilst the constitutive
      trafficking of proteins is independent of actin. Taken together, our findings
      indicate that at least two TGN sub-domains are regulated by separate cytoskeletal
      dynamics involving actin and tubulin.

PMID- 14668140
TI  - Ion channels formed in planar lipid bilayers by the dipteran-specific Cry4B
      Bacillus thuringiensis toxin and its alpha1-alpha5 fragment.
AB  - Trypsin activation of Cry4B, a 130-kDa Bacillus thuringiensis (Bt) protein,
      produces a 65-kDa toxin active against mosquito larvae. The active toxin is made
      of two protease resistant-products of ca. 45 kDa and ca. 20 kDa. The cloned 21
      kDa fragment consisting of the N-terminal region of the toxin was previously
      shown to be capable of permeabilizing liposomes. The present study was designed
      to test the following hypotheses: (1) Cry4B, like several other Bt toxins, is a
      channel-forming toxin in plannar lipid bilayers; and (2) the 21-kDa N-terminal
      region, which maps for the first five helices (alpha1-alpha5) of domain 1 in
      other Cry toxins, and which putatively shares a similar tri-dimensional
      structure, is sufficient to account for the ion channel activity of the whole
      toxin. Using circular dichroism spectroscopy and planar lipid bilayers, we showed
      that the 21-kDa polypeptide existed as an alpha-helical structure and that both
      Cry4B and its alpha1-alpha5 fragment formed ion channels of 248 +/- 44 pS and 207
      +/- 23 pS, respectively. The channels were cation-selective with a potassium-to
      chloride permeability ratio of 6.7 for Cry4B and 4.5 for its fragment. However,
      contrary to the full-length toxin, the alpha1-alpha5 region formed channels at
      low dose; they tended to remain locked in their open state and displayed
      flickering activity bouts. Thus, like the full-length toxin, the alpha1-alpha5
      region is a functional channel former. A pH-dependent, yet undefined region of
      the toxin may be involved in regulating the channel properties.

PMID- 14668141
TI  - The effects of cognitive abilities on driving in people with Parkinson's disease.
AB  - OBJECTIVE: The aim was to develop a cognitive screening procedure, which could be
      used to identify cognitive problems in patients with Parkinson's disease, which
      might affect their safety to drive. DESIGN: Two group comparison of those found
      safe to drive and those found unsafe. SETTING: People living in the community who
      were attending an outpatient Movement Disorders clinic or who had been referred
      to a Regional Mobility Centre. PARTICIPANTS: Fifty-one people with Parkinson's
      disease who were driving or who wished to resume driving. The 41 men and 10 women
      were aged 44 - 85 years (mean 64.4 SD 9.1). MAIN MEASURES: Webster's Rating
      Scale, Unified Parkinson's Disease Rating Scale motor examination, Stroke Drivers
      Screening Assessment, Adult Memory and Information Processing Battery, Stroop,
      Paced Auditory Serial Addition Task and a Tapping task. RESULTS: The unsafe
      drivers were significantly more disabled, as assessed on Webster's Scale, than
      those who were found safe to drive. There were no significant differences in the
      cognitive abilities of safe and unsafe drivers. The most common faults, which
      caused drivers to be judged unsafe, were lack of observations to the side at
      junctions, poor positioning on the road and poor driving on roundabouts. There
      were significant correlations (p < 0.05) between driving ability and performance
      on the SDSA Dot Cancellation task and the AMIPB Story Recall and Information
      Processing A. CONCLUSIONS: Cognitive abilities were not found to be associated
      with fitness to drive in people with Parkinson's disease. Webster's Rating Scale
      differentiated between safe and unsafe drivers. This could be used to determine
      who to refer to a mobility centre for advice on fitness to drive.

PMID- 14668142
TI  - Prevalence of post-stroke depression in an Irish sample and its relationship with
      disability and outcome following inpatient rehabilitation.
AB  - PURPOSE: (1). To examine the prevalence of depressive symptoms and operationally
      defined depressive disorder (major depression) in an Irish sample of subjects
      undergoing inpatient rehabilitation following their first stroke. (2). To
      investigate factors predictive of depression following stroke. (3). To examine
      the relationship between post-stroke depression and outcome following inpatient
      rehabilitation. METHODS: Fifty consecutive patients meeting inclusion criteria
      who were admitted for inpatient rehabilitation to a specialised unit following
      their first stroke were prospectively studied. INCLUSION CRITERIA: first stroke 3
      - 12 months previously, lesion identified on CT or MRI, age 18 - 65 years, at
      least some sensory/motor impairment, no pre-existing disabling condition and
      Barthel Index score > 14 prior to stroke. Mood (Center for Epidemiologic Studies
      Depression scale, Hamilton Depression Rating Scale, DSM-IV diagnostic criteria
      for Major Depressive Disorder), Cognition (Mini-Mental State Examination) and
      Disability (Barthel Index, Rankin Disability Scale) were assessed one week after
      admission (baseline) and again after 2 months of rehabilitation. Outcome was
      measured as effectiveness of rehabilitation (Shah et al., 1990) and length of
      inpatient stay (LOS). RESULTS: 10/50 (20%) of the sample met criteria for major
      depressive disorder on admission. The best predictor of depression was gender,
      with females having a two-fold higher rate of both subjectively reported and
      objectively rated depressive symptoms. Depression was unrelated to baseline
      Barthel Disability, side of lesion or previous psychiatric history. The best
      predictor of effectiveness of rehabilitation was baseline Barthel Disability
      score. Depression did not predict either effectiveness or LOS. CONCLUSION: (1).
      Major depression is common in subjects undergoing rehabilitation following their
      first stroke. (2). Females appear to be especially at risk, possibly reflecting
      an increased general risk of depression. (3). Depression in our sample was not
      related to functional disability following stroke or early functional outcome
      following rehabilitation.

PMID- 14668143
TI  - Impairments, disabilities and health related quality of life after treatment for
      breast cancer: a follow-up study 2.7 years after surgery.
AB  - PURPOSE: The aim of this study was to assess impairments, disabilities and health
      related Quality of Life (QOL) after treatment of breast cancer and to analyse the
      relationship between treatment modalities, impairments, disabilities and health
      related QOL. METHOD: Fifty-five patients who underwent a modified radical
      mastectomy or a segmental mastectomy with axillary lymph node dissection were
      retrospectively assessed with a mean follow up of 2.7 years after treatment.
      Impairments were assessed by means of measuring active shoulder range of motion,
      grip strength, arm volume and pain. Disabilities were assessed by means of the
      Shoulder Disability Questionnaire (SDQ) and health related QOL was assessed by
      means of the RAND 36-item Health Survey (RAND-36). SETTING: University Hospital
      Groningen (The Netherlands). RESULTS: Pain (60%) and reduction of grip-strength
      (40%) were the most frequent impairments found. The prevalence of impaired range
      of motion and oedema was 9 - 16% respectively 15%. Mean group score of the SDQ
      was 33.7 (sd: 32.1) and mean scores of the RAND-36 differed significantly for
      physical functioning, vitality and health perception to that of a female norm
      group. Radiotherapy and chemotherapy were significant factors in the prediction
      of impaired range of motion. Pain and restricted range of motion explained 61%
      respectively 12% of the variance in disability (SDQ). In the prediction of health
      related QOL, pain, grip strength and arm volume were significant factors
      respectively in six, three and two domains. CONCLUSIONS: Pain is the most
      frequent assessed impairment after breast cancer treatment with strong
      relationship to perceived disability and health related QOL. Disability is mild
      and health related QOL (RAND-36) differed in three of the nine domains with a
      female norm group.

PMID- 14668144
TI  - Rehabilitation following hip fracture surgery: a comparative study of females and
      males.
AB  - PURPOSE: To compare patient, fracture and rehabilitation variables between male
      and female patients during the rehabilitation period immediately following
      surgical repair of hip fracture (HF). METHODS: A prospective cohort study was
      conducted in a rehabilitation geriatric ward in a tertiary university hospital in
      southern Israel. The study group consisted of 808 elderly patients, 65 years of
      age or older, selected for hospitalized rehabilitation following surgery for HF.
      The measurements included functional studies by the Functional Independence
      Measure (FIM) scale, mental status by Folstein Minimental Test and Clock Drawing
      Test, Geriatric Depression Screening Scale (GDS), demographic and social
      parameters, laboratory tests, length of rehabilitation, complications and
      mortality during rehabilitation. RESULTS: Six hundred and fourteen patients (76%)
      were women and 194 (24%) were men. The mean age ( +/- SD) of the women was 78.4
      +/- 7.1 years and of the men was 77.8 +/- 7.5 (NS). There were no significant
      differences between women and men in terms of the anatomic site of the fracture
      or the type of surgery, the complication rate or mortality during rehabilitation,
      the length of time needed for rehabilitation, the framework to which the patient
      was discharged, FIM values before the HF, on admission and at the end of
      rehabilitation, or the difference between FIM scores at these last two points in
      time. CONCLUSIONS: In selected elderly patients with HF gender does not affect
      variables associated with hip fracture, the rehabilitation process immediately
      following the fracture, or the results of rehabilitation.

PMID- 14668145
TI  - Long-term outcome of equestrian injuries in children.
AB  - PURPOSE: To investigate the possible development of long-term disabilities
      arising from paediatric equestrian injuries. METHOD: All patients, aged 17 years
      or younger, treated in a hospital setting because of an equestrian injury during
      a five-year period received a questionnaire. A reference population and healthy
      friends served as controls. RESULTS: Four years post-injury, 41 of the 100
      respondents still experienced disabilities following the injury. The median
      Injury Severity Score was 4. Absenteeism from school lasted 2 weeks, and from
      horse riding, 4 months. Compared to the reference population, the results of the
      Child Health Questionnaire were poorer considering most of its subscales. In
      comparison with the friends, the patients only scored lower on 'physical
      functioning'. The risk factors concerning poor long-term outcomes were being an
      advanced rider, sustaining injuries other than fractures of the extremities or
      sustaining subsequent injuries following the riding accident. CONCLUSIONS:
      Although equestrian injuries in children are minor to moderate in their severity,
      these injuries are significant considering that a large proportion of patients
      experience long-term disabilities.

PMID- 14668146
TI  - Impact of middle ear effusion on balance performance in children.
AB  - Middle ear effusion (MEE) is a common childhood disease characterized by
      accumulation of fluid in the middle ear. MEE treatment focuses on the resultant
      conductive hearing loss. Recently, researchers have investigated the potential
      effects of MEE on balance. PURPOSE: The purpose of this study was to compare
      balance of children with MEE to that of healthy children and to examine whether a
      relation exists between balance skills and the degree of muscle strength.
      METHODS: Twenty children with MEE and twenty healthy children aged 4.5 - 7.5
      years underwent balance and strength sub-tests of Bruininks - Oseretsky Test of
      Motor Performance (BOTMP) and electronystagmography recordings (ENG). Parents
      completed a questionnaire designed to elicit their perceptions of their child's
      balance abilities in daily living activities. RESULTS: MEE children performed
      significantly worse than did the control group on BOTMP balance sub-test. BOTMP
      strength subtest indicated that children with MEE had poorer muscle strength than
      the control group, although the difference was not significant. ENG results
      showed no pathologic recordings in both study group and control group. Finally, a
      significant correlation was found between parents' responses on the questionnaire
      and their child's performance on BOTMP balance subtest. CONCLUSIONS: MEE may
      negatively impact children's balance, while muscle strength is less affected.
      Furthermore, the BOTMP appears to be a sensitive assessment of balance
      disturbances in children with MEE.

PMID- 14668147
TI  - The reliability and validity of the Xhosa version of the EQ-5D.
AB  - SETTING: This study aimed to examine the reliability and validity of the Xhosa
      version of the EQ-5D, a Health Related Quality of Life measure which is often
      used as an outcome measure in clinical trials, within an urban Xhosa speaking
      population. SUBJECTS AND OUTCOME MEASURES: The test-retest reliability was
      examined on a community and institutional sample of 88 subjects, who were
      interviewed twice, one week apart. Forty-nine out- and in-patients participated
      in the second part of the study, in which the concurrent validity of the EQ-5D
      against existing Xhosa measures of similar domains as the EQ-5D was examined.
      RESULTS: The Intraclass correlation (ICC) co-efficients between the first and
      second interviews ranged from 0.39 to 0.75 in different domains. The ICC for the
      Visual Analogue Scale of health state was 0.63. In the validity study, those who
      reported no problems with mobility demonstrated a significantly higher gait
      velocity. There was a significant difference between the rank ordering of scores
      on the four domains of self-care, usual activities pain/discomfort and
      anxiety/depression and the scores obtained on the 'gold standard' tests. RESULTS
      AND CONCLUSIONS: It is concluded that, although some domains might need to be
      examined further, the Xhosa EQ-5D is a valid and reliable instrument with which
      to determine HRQoL in an urban Xhosa speaking population. In order to ensure
      validity of results in multicultural research and drug trials, it is essential
      that more outcome measures are subjected to rigorous translation and testing of
      validity and reliability.

PMID- 14668148
TI  - Reliability, validity and factor structure of the upper limb subscale of the
      Motor Assessment Scale (UL-MAS) in adults following stroke.
AB  - PURPOSE: The upper limb items of the Motor Assessment Scale (MAS) have been shown
      to be a sensitive, valid and reliable measure of upper limb function for adults
      following stroke, however the validity and reliability of summing these items
      into an independent subscale has not yet been evaluated. The stability, internal
      consistency and construct validity of the upper limb MAS subscale (UL-MAS) was
      assessed in this study. METHOD: Twenty-seven inpatients following stroke (mean
      age = 67 years, range = 40 - 80) were sampled from an acute, inpatient
      rehabilitation setting. Patients were evaluated with 'Upper Arm Function', 'Hand
      Movements', and 'Advanced Hand Activities' items of the MAS by masked
      physiotherapists who had received standardized training in administration of the
      MAS. RESULTS: All items were explained by one factor on confirmatory factor
      analysis and correlated significantly with one another and with the composite
      (summed total) score. Internal consistency analysis produced a Cronbach's alpha
      of 0.83 which did not benefit from removal of any items. CONCLUSIONS: The
      acceptable internal consistency score obtained verifies the validity and
      reliability of using the UL-MAS as an independent scale. This study has also
      verified the construct validity of the UL-MAS subscale and provides a valuable
      extension of previous work, which together demonstrates the value of the UL-MAS
      as a responsive, valid and reliable measure of upper limb function in adults
      following stroke. The UL-MAS produced a single, composite score that could be
      interpreted as a total score for upper limb function in this population.

PMID- 14668149
TI  - Effects of biofeedback treatment on gait in children with cerebral palsy.
AB  - PURPOSE: We evaluated the effectiveness of biofeedback treatment on gait function
      in children with cerebral palsy. METHOD: Thirty-six children with spastic
      cerebral palsy and dynamic equinus deformity were included in the study. The
      biofeedback group consisted of 21 children who each received EMG biofeedback
      training plus conventional exercise programme. The control group consisted of 15
      children who each received conventional exercise programme only. Active range of
      motion of the ankle joints, muscle tone of plantar flexors, and gait function of
      the children were evaluated and compared. RESULTS: The biofeedback group
      displayed statistically significant improvements regarding tonus of plantar
      flexor muscles and active ROM of ankle joints (p < 0.000 for all parameters).
      Gait function showed statistically significant progress in both of the groups,
      but the biofeedback group was superior to controls. CONCLUSIONS: Children with
      cerebral palsy and dynamic equinus deformities may benefit from biofeedback
      treatment for ambulation.

PMID- 14668150
TI  - Barriers to accessing safe motherhood and reproductive health services: the
      situation of women with disabilities in Lusaka, Zambia.
AB  - PURPOSE: To ascertain how well health services in Lusaka, Zambia currently meet
      the safe motherhood and reproductive health care needs of women who have physical
      impairment leading to disability. METHODS: A qualitative study was conducted in
      Lusaka, Zambia. In-depth tape-recorded interviews were conducted with 24
      purposively selected women with disabilities and with 25 safe
      motherhood/reproductive public sector health service providers. Qualitative
      analysis was conducted using NVivo software. RESULTS: Women with disabilities
      encounter various social, attitudinal and physical barriers to accessing safe
      motherhood and reproductive health (RH) services in this particular setting. The
      strong desire for children and affection can increase vulnerability to sexual
      exploitation. At the same time, a generalized assumption among reproductive
      health service providers that women with disabilities will not be sexually
      active, and not require RH services, leads to increased vulnerability to sexually
      transmitted infection including HIV. Once pregnant, traditional beliefs about
      transmission of disabilities can create barriers to integration in ante-natal
      clinics. Nurse-midwives' fear of delivery complications in women with physical
      impairments can also result in routine over-referral to a tertiary maternity
      facility which is outside the locality and harder for women with mobility
      limitations to get to. CONCLUSION: Greater understanding of the influences
      underpinning societal attitudes towards sexuality and disability in this setting,
      and more extensive communication between health care staff and women with
      disabilities would facilitate positive action towards improving safe motherhood
      and reproductive health services for women with disabilities.

PMID- 14668151
TI  - Chloronaphthalenes as food-chain contaminants: a review.
AB  - Chloronaphthalenes are dioxin-like environmental and food contaminants that for
      many years have undergone diffusion from dispersed emission sources of various
      types on a global scale. When released into ambient air like many other
      semivolatile organohalogen compounds, chloronaphthalenes undergo various
      processes and pathways including sequestering by plant vegetation and biota.
      Recently available data indicate that sequestering rates of chloronaphthalenes by
      plant biomass and including edible plants as well as concentrations in food
      sources of plant origin can be greater than was earlier predicted. Additionally,
      it become known very recently that in some highly industrialized countries such
      as Japan, Canada and the UK, the technical chloronaphthalene mixtures are still a
      subject of industrial and commercial interest, even if such activities are
      illegal. Recent achievements in HRGC-HRMS have enabled elucidation and
      quantification of the chloronaphthalene congener composition in environmental
      matrices, food sources and technical mixtures, their persistency, environmental
      fate, accumulation in biota and potential for food chain biomagnification.
      However, at the same time this raised questions regarding human exposure to these
      compounds. By the late 1990s, these developments added to the relatively rapidly
      growing knowledge on these compounds and especially individual congener
      properties such as thermodynamic and physicochemical features and toxicity.
      Multistage fractionation has recently enabled routine congener-specific
      quantification of tetra- to octachloronaphthalene in various matrices. This paper
      reviews the literature on chloronaphthalenes as food chain contaminants and
      covers their origin, physicochemical properties, toxicity, environmental
      concentrations and persistency, and homologue group and congener composition in
      various matrices. The review also covers distribution in environmental
      compartments and subsequent fate and migration to food sources, as well as the
      magnitude of dietary intake and human body concentrations. Data on
      chloronaphthalene residues in food, however, are still scare, an exception being
      seafood sources and recently available data from Spain on their concentrations in
      staple foods and dietary intake.

PMID- 14668153
TI  - Assessment of food intake input distributions for use in probabilistic exposure
      assessments of food additives.
AB  - A key component of a food chemical exposure assessment using probabilistic
      analysis is the selection of the most appropriate input distribution to represent
      exposure variables. The study explored the type of parametric distribution that
      could be used to model variability in food consumption data likely to be included
      in a probabilistic exposure assessment of food additives. The goodness-of-fit of
      a range of continuous distributions to observed data of 22 food categories
      expressed as average daily intakes among consumers from the North-South Ireland
      Food Consumption Survey was assessed using the BestFit distribution fitting
      program. The lognormal distribution was most commonly accepted as a plausible
      parametric distribution to represent food consumption data when food intakes were
      expressed as absolute intakes (16/22 foods) and as intakes per kg body weight
      (18/22 foods). Results from goodness-of-fit tests were accompanied by lognormal
      probability plots for a number of food categories. The influence on food additive
      intake of using a lognormal distribution to model food consumption input data was
      assessed by comparing modelled intake estimates with observed intakes. Results
      from the present study advise some level of caution about the use of a lognormal
      distribution as a mode of input for food consumption data in probabilistic food
      additive exposure assessments and the results highlight the need for further
      research in this area.

PMID- 14668152
TI  - Structure determination of minor red pigment in carthamus red colorant isolated
      by preparative LC/MS.
AB  - Carthamin is a well-known major pigment in carthamus red colourant. When analysed
      by HPLC on an ODS column, the colorant separated into two distinct reddish
      pigments, with both components having almost identical photodiode array spectra.
      LC/MS analysis suggested one of the compounds was carthamin, whilst the other was
      an unknown minor pigment. The minor pigment was purified and isolated from the
      colorant by preparative LC/MS collecting the faction based on monitoring the
      deprotonated molecule [M-H](-) m/z 953 in electrospray negative-ion mode. The
      structure was elucidated as a hydroxyethyl ether of carthamin, a novel compound,
      by means of NMR and HR-FAB-MS analyses.

PMID- 14668154
TI  - Comparative evaluation of the performance of two commercial kits for the
      detection of central nervous system tissue in meat.
AB  - The ScheBo Brainostic test, which detects neuron-specific enolase by Western
      blotting, and the r-Biopharm Ridascreen Risk Material ELISA test, which detects
      the presence of glial fibrillary acidic protein, were evaluated using meats
      containing spinal cord and brain central nervous system (CNS) tissue from ovine
      and bovine species. The meats were pork, cooked pork sausage, raw minced lamb and
      cooked minced lamb. Spiking of the CNS tissue ranged from 0.01 to 5%. No false
      positives were observed with either test using the manufacturers' analytical
      protocols. The presence or absence of CNS tissue was correctly determined in 20
      of 20 samples using the ScheBo Brainostic test and 18 of 20 samples using the
      Ridascreen tests. When results were placed in categories according to quantity of
      CNS tissue detected, 19 of 20 samples were classified correctly using the
      Brainostic test and 14 of 20 samples using the Ridascreen test. Both kits were
      considered appropriate for reporting the presence of 1% or more CNS tissue in
      meat products, but the ScheBo Brainostic test was more consistent at detecting
      the presence of CNS tissues below the 1% level. Overall, the format of the
      Ridascreen test was technically easier to use, and the data simpler to interpret.

PMID- 14668155
TI  - Distribution of multiple pesticide residues in apple segments after home
      processing.
AB  - The effects of washing, storing, boiling, peeling, coring and juicing on
      pesticide residue were investigated for field-sprayed Discovery and Jonagold
      apples. Residues of chlorpyrifos, cypermethrin, deltamethrin, diazinon,
      endosulfan, endosulfan sulfate, fenitrothion, fenpropathrin, iprodione, kresoxim
      methyl, lambda-cyhalothrin, quinalphos, tolylfluanid and vinclozolin in the
      processed apples were analysed by gas chromatography. Statistical analysis showed
      that reductions of 18-38% were required to obtain significant effects of
      processing practices, depending on pesticide and apple variety. Juicing and
      peeling the apples significantly reduced all pesticide residues. In the case of
      detectable pesticide residues, 1-24% were distributed in the juice and in the
      peeled apple. None of the pesticide residues was significantly reduced when the
      apples were subject to simple washing or coring. Storing significantly reduced
      five of the pesticide residues: diazinon, chlorpyrifos, fenitrothion, kresoxim
      methyl and tolylfluanid, by 25-69%. Residues of the metabolite endosulfan sulfate
      were increased by 34% during storage. Boiling significantly reduced residues of
      fenitrothion and tolylfluanid by 32 and 81%, respectively. Only a few of the
      observed effects of processing could be explained by the physical or chemical
      characteristics of the pesticides. No differences in effect of processing due to
      apple variety were identified.

PMID- 14668156
TI  - Determination of the herbicide isoproturon in cereal grains and pasta by LC with
      LC/MS confirmation.
AB  - A method was developed for the determination of the herbicide isoproturon in
      wheat, maize, oats and pasta, with a limit of determination of 0.05 mg kg(-1).
      Isoproturon was extracted from moistened samples using a mixture of acetone,
      hexane and dichloromethane. The resulting extract was cleaned-up by solid-phase
      extraction using aminopropyl-bonded silica cartridges and analysed by reversed
      phase liquid chromatography with photodiode array detection. Confirmation was by
      electrospray liquid chromatography-mass spectrometry. Recoveries from seven
      samples of each of the four matrices spiked with isoproturon at 0.05 and 0.5 mg
      kg(-1) were in the range 88-104%. The method was used to monitor cereal grains
      and pasta as part of the UK food monitoring programme.

PMID- 14668157
TI  - Ochratoxin A in raisins and currants: basic extraction procedure used in two
      small marketing surveys of the occurrence and control of the heterogeneity of the
      toxins in samples.
AB  - A basic extraction procedure for analysis of ochratoxin A (OTA) in currants and
      raisins is described, as well as the occurrence of OTA and a control of
      heterogeneity of the toxin in samples bought for two small marketing surveys
      1999/2000 and 2001/02. Most samples in the surveys were divided into two
      subsamples that were individually prepared as slurries and analysed separately.
      The limit of quantification for the method was estimated as 0.1 microg kg(-1) and
      recoveries of 85, 90 and 115% were achieved in recovery experiments at 10, 5 and
      0.1 microg kg(-1), respectively. Of all 118 subsamples analysed in the surveys,
      96 (84%) contained ochratoxin A at levels above the quantification level and five
      samples (4%) contained more than the European Community legislation of 10 microg
      kg(-1). The OTA concentrations found in the first survey were in the range < 0.1
      19.0 microg kg(-1) with a median concentration of 0.9 microg kg(-1). In the
      2001/02 study, the range was < 0.1-34.6 microg kg(-1) with a median of 0.2 microg
      kg(-1). Big differences were often achieved between individual subsamples of the
      original sample, which indicate a wide heterogeneous distribution of the toxin.
      Data from the repeatability test as well as recovery experiments from the same
      slurries showed that preparation of slurries as described here seemed to give a
      homogeneous and representative sample. The extraction with the basic sodium
      bicarbonate-methanol mixture used in the surveys gave similar or somewhat higher
      OTA values on some samples tested in a comparison with a weak phosphoric acid
      water-methanol extraction mixture.

PMID- 14668158
TI  - Aflatoxin B1 and its interconverting metabolite aflatoxicol in milk: the
      situation in Mexico.
AB  - Between 1996 and 1998, 580 litres of milk in Mexico were surveyed for aflatoxin
      B(1) (AFB(1)) and its metabolite aflatoxicol (AFL), which are mutagenic and
      carcinogenic mycotoxins that interconvert AFB(1)-AFL-AFB(1). The seven most
      consumed brands from different regions of Mexico included pasteurized and
      ultrapasteurized milk with four different fat levels: whole fat (28-33 g l(-1)),
      half-skimmed (10-20 g l(-1)), light (1-4 g l(-1)) and with vegetable oil (33 g l(
      1)). Aflatoxins in each sample were concentrated with total aflatoxin
      immunoaffinity columns and quantitated by high-performance liquid chromatography.
      A milk sample was considered contaminated if it contained >/=0.05 microg l(-1)
      AFL. Pasteurization and ultrapasteurization of milk did not control contamination
      with AFL, which was present in 13% of samples at >/=0.05 microg l(-1) and in 8%
      at >/=0.5 microg l(-1), with a range of AFL from 0 to 12.4 microg l(-1). AFB(1)
      was present mainly in traces (0-0.4 microg l(-1)). The safest milk in relation to
      AFL contamination was imported milk powder with vegetable oil. There was a
      significant correlation between contamination of milk with AFL and the autumn
      (p<0.0002); the fat content was not significant.

PMID- 14668159
TI  - European survey of contamination of homogenized baby food by epoxidized soybean
      oil migration from plasticized PVC gaskets.
AB  - The results are reported of a European survey of the contamination of baby food
      with epoxidized soyabean oil (ESBO). Fat from the sample was extracted,
      transmethylated and derivatized for analysis by gas chromatography/mass
      spectrometry (GC/MS). Analysis was carried out of 248 samples of various types of
      foodstuffs from the 15 European Union Member States as well as Switzerland. ESBO
      was found in 95 of 248 samples analysed at levels from 1.5 to 135.2 mg kg(-1).
      The highest concentrations were found in main dish mixed foods such as vegetables
      and meat or carbohydrate- and vegetable-based mixes. Levels exceeded 30 mg kg(-1)
      in 15% of the samples, and 4% exceeded the overall migration limit fixed for
      plastics in the European Union of 60 mg kg(-1). This level of contamination is
      significant, confirming results from previous surveys and indicating a risk for
      the tolerable daily intake to be exceeded. These results suggest that an emphasis
      must be placed for more systematic research with a focus on the parameters for
      migration.

PMID- 14668160
TI  - Perceptual lane width, wide perceptual road centre markings and driving speeds.
AB  - The possibility that driving speeds could be reduced through the use of lane
      delineation was explored. Using a high-fidelity driving simulator, 28 experienced
      drivers were measured on seven two-lane rural roads with lane widths of 3.6, 3.0,
      or 2.5 m, and with either a standard centreline (control), a wide painted hatched
      road centre marking, or a wide white gravel road centre marking. Driving speeds
      were reduced on the narrowest lane width road, and further reduced on straight
      road sections that contained the centre marking with painted hatching. It was
      concluded that the narrow lane width increased steering workload and reduced
      speeds through a speed-steering workload trade-off, whilst the hatched road
      centre marking enhanced peripheral visual speed perception, leading to higher
      speed estimations and slower speeds. Therefore, narrowing the lane width below
      3.0 m by using a painted hatched road centre marking should be an effective way
      to reduce driving speeds.

PMID- 14668161
TI  - Factors affecting performance on a target monitoring task employing an automatic
      tracker.
AB  - The experiments in this paper examined the extent to which performance on a task
      employing an automatic tracker was similar to performance on tasks employing
      other types of automation that have been studied more extensively. Automated
      target tracking is being used in many sensor and navigation systems to improve
      performance and help the operator cope with increased data loads. With many
      automated systems these goals are not met. In particular, the operator often
      misses errors made by the automated system and may report no decrease in
      workload. Several hypotheses have been offered for the operator's failure to
      monitor an automated system adequately. These include lack of experience with the
      manual task, a vigilance decrement, complacency, and inappropriate level of
      automation. The relevance of each of these hypotheses to failure to monitor an
      automatic tracker adequately was examined. Performance and perceived workload on
      a target tracking task employing an automatic tracker, in which participants had
      to detect and then update the position of several targets (e.g. ships) at regular
      intervals, were measured as a function of number of targets, training with the
      manual task, experience, and time on task. The results suggested that failure to
      detect errors made by the automated system was due largely to the lack of
      visibility of the automation errors relative to other errors. However,
      complacency could not be ruled out entirely. Unlike some other tasks, the
      availability of a reliable automatic tracker did lead to a substantial reduction
      in perceived workload.

PMID- 14668162
TI  - Display-control compatibility: the relationship between performance and judgments
      of performance.
AB  - This study examined whether people can judge the usability of display-control
      mappings. Participants identified one of two alternatives which were presented in
      a questionnaire. Several types of stimuli were tested, ranging from simple shapes
      to semantic stimuli. Choices were found to be predominately correct when
      usability was defined by an unambiguous spatial relationship between displays and
      controls. In contrast, estimates were less accurate for items which did not
      solely rely on spatial congruence. The findings were interpreted in terms of the
      factors that need to be considered for judgments to be free of error.

PMID- 14668163
TI  - Muscle activity during patient transfers: a preliminary study on the influence of
      lift assists and experience.
AB  - The purpose of this study was to examine muscle activity patterns during patient
      handling during manual transfers, and transfers using floor and ceiling lifts.
      EMG patterns during transfers from bed to wheelchair and wheelchair to bed as
      well as patient repositioning in novices and experienced participants were
      examined. Surface EMG was recorded from the upper and lower erector spinae,
      latissimus dorsi and trapezius muscles bilaterally. Overall, normalized mean and
      peak muscle activity were lowest using the ceiling lift, increasing with the
      floor lift, which were lower than manual transfers (novices: all p < 0.01).
      Experienced patient handlers demonstrated approximately two times greater
      trapezius and latissimus dorsi activity than novices, combined with lower mean
      erector spinae activity (p < 0.05, for most tasks). Integrated EMG for all
      muscles was directly proportional to the transfer time and was lowest during the
      manual transfer followed by the ceiling lift, with the floor lift being highest.
      The difference between the muscle activity patterns between the experienced and
      novice patient handlers may suggest a learned behaviour to protect the spine by
      distributing load to the shoulder. Further examination of the muscle activation
      patterns differences between experience levels could improve training techniques
      to develop better patient handling strategies.

PMID- 14668164
TI  - Shiftwork experience and the value of time.
AB  - Dissatisfaction with shiftwork has been shown to increase with age and work
      experience. The objective was to determine if differences in preferred paid work
      time existed between shiftworkers with different lengths of shiftwork experience
      and age-matched non-shiftworkers (controls). A questionnaire was used to
      determine how controls and shiftworkers with different shiftwork experience
      perceived the value of preferred work time across the week. Participants were
      required to value each hour across the days of the week on a scale from 0 (least
      preference) to 10 (highest preference). Data were analysed across groups to
      produce mean and standard deviation matrices. Unpaired t-tests determined
      significant differences between groups. This study found that preferred hours-of
      work change with years of shiftwork experience. For shiftworkers in their first 5
      years and those in their 30th-year-plus of shiftwork, night work was a low
      priority. Shiftworkers with 17 - 30 years experience indicated a preference for
      work any time across the week. Overall, shiftworkers extended their preferred
      work hours to include the evenings and weekend. Controls adhered more strongly to
      current societal norms. The results suggest that a person initially undertaking
      shiftwork may well be one with a less restrictive perception of time and its use,
      however, this perception may alter over time.

PMID- 14668165
TI  - Effect of single and double strap backpacks on lung function.
AB  - Carrying heavy and moderate military loads in backpacks or as body armour
      compresses the chest, causing a change in lung function that is typical of a
      restrictive ventilatory impairment. It is not known if a lighter backpack load of
      only 6 kg, such as is typical of loads carried by students, will have a similar
      effect on lung function. There have been no studies examining whether backpacks
      of different strapping styles have an effect on lung function. Several designs of
      student backpack have recently been introduced to the market. One of the most
      popular is a single-strap backpack. This study examined Forced Vital Capacity
      (FVC), Forced Expiratory Volume in one second (FEV1), FEV1.FVC( - 1)% and Peak
      Expiratory Flow (PEF) in 13 participants (4 males, 9 females) wearing each of two
      6 kg backpacks, one with two shoulder straps (a Double Strap Backpack (DSB)) and
      the other with a single strap (a Single Strap Backpack (SSB)) worn across the
      shoulder and chest. In comparison with the control of no pack (N), SSB
      significantly reduced FVC (by 3.94%, p = 0.006) but there were no significant
      differences in FEV1, FEV1. FVC( - 1)% and PEF. The DSB also significantly reduced
      FVC (by 1.97%, p = 0.034) but no significant differences were found in FEV1,
      FEV1. FVC( - 1)% and PEF measures. In comparison with DSB, the SSB was associated
      with a significantly lower FVC (by 2.05%, p = 0.049) and FEV1 (by 1.88%, p =
      0.029) but there were no significant changes in FEV1. FVC( - 1)% and PEF. It is
      concluded that a backpack load of 6 kg could produce a mild restrictive type of
      ventilatory impairment in lung function. This effect was greater for a single
      cross-chest strap than for a more conventional double strap harness.

PMID- 14668166
TI  - Effect of backpack fit on lung function.
AB  - Carrying loads close to the trunk with a backpack causes a restrictive type of
      change in lung function in which Forced Vital Capacity (FVC) and Forced
      Expiratory Volume in 1 s (FEV1) are reduced without a corresponding decrement in
      the FEV1.FVC( - 1) %. It is not known whether this is due to the weight of the
      load acting on the chest or to the tightness of fit of the shoulder and chest
      straps and waist belt of the pack harness. This study examined FVC, FEV1,
      FEV1.FVC( - 1) %, peak expiratory flow (PEF), forced expiratory flow between 0.2
      and 1.2 s (FEF0.2 - 1.2) after the start of expiration and between 25 and 75% of
      each FVC (FEF25 - 75%) in 12 healthy males wearing a 15 kg backpack in which the
      shoulder and chest straps and hip belt were loosened by 3 cm from a 'comfort fit'
      to achieve a 'loose pack' fit (LPF) and tightened by 3 cm from CF to achieve a
      'tight pack' fit (TPF). In comparison with the control condition of no pack, a
      loose pack fit significantly reduced FVC (by 3.6%, p < 0.01), FEV1 (by 4.3%, p <
      0.01) and FEF25 - 75% (by 8.4%, p < 0.01). A tight pack fit significantly reduced
      FVC (by 8.1%, p < 0.01) and FEV1 (by 9.1%, p < 0.001). It also significantly
      reduced FEF0.2 - 1.2 (by 7.3%, p < 0.05) and FEF25 - 75% (by 21%, p < 0.01). In
      comparison with a loose pack fit, the tight pack fit was associated with a
      significantly lower FVC (by 4.6%, p < 0.01), FEV1 (by 5.0%, p < 0.01), FEF25 -
      75% (by 13.8%, p < 0.01) and a fall in FEF0.2 - 1.2 (by 5.5%). The latter was
      approaching significance (p = 0.077). There were no significant changes in
      FEV1.FVC( - 1)% and PEF. It is concluded that tightening the fit of a backpack
      significantly affects lung function in a manner that is typical of a restrictive
      change in lung function and is very similar in pattern to that of wearing a
      loosely fitted loaded backpack. The effect of tightness of fit is additional to
      that due to the weight of the load alone and may also reduce expiratory flow at
      low lung volumes.

PMID- 14668167
TI  - Determination of worker physiological cost in workspace reach envelopes.
AB  - Oxygen uptake (VO2), heart rate (HR) and myoelectric activity (EMG) were measured
      while performing a repetitive task in the normal, maximum and extreme workspace
      reach envelopes. The VO2 and HR increased significantly from the normal to the
      maximum to the extreme workspace reach envelope. The average increases in VO2
      when compared to the normal workspace were 19 and 52%, respectively. The
      corresponding average increases in HR were 6 and 14%, respectively. The increase
      in EMG for anterior deltoid, upper trapezious and erector spinae showed a
      significant increase from normal to maximum and from maximum to extreme
      workspaces. The average increases in EMG for anterior deltoid, upper trapezious
      and erector spinae, compared to the normal workspace were 96, 37 and 48%
      respectively for the maximum workspace and 193, 95 and 106% for the extreme
      workspace, respectively. The research indicated for the first time that during
      task performance, worker physiological cost would increase significantly with the
      increase in workspace reach levels.

PMID- 14668168
TI  - Kinematics of head-trunk movements while entering and exiting a car.
AB  - The study of free and natural accessibility movements for a medium-sized car was
      carried out, recording the motor performances of ten participants by means of a
      motion analysis system. The experimental protocol used passive markers to
      implement a two-segment biomechanical model for the analysis of the head-trunk
      complex. The kinematic variables quantify the motor patterns, and showed specific
      features that can be related to the individual anthropometric characteristics and
      to the car geometry differences: tall participants used a neck flexion and a
      leftwards bending of the head, while short participants extended the neck and
      bent the head to the right. The different seat positions (short participants move
      forwards the seat) along with the principal need to avoid any body interference
      with the car, can explain the observed strategies. From the wider analysis of the
      movements in relation to the vehicle's features and to the anthropometric size of
      the participants, this approach could lead to an extension of the design criteria
      for those structural components of the car which have been demonstrated to
      significantly influence the human-machine interaction.

PMID- 14668170
TI  - Image parameters for driving with indirect viewing systems.
AB  - Indirect viewing systems such as tv cameras can potentially support drivers under
      low visibility conditions or when the driver's field of view (FOV) is restricted.
      In three experiments, we identified the critical image parameters of such systems
      on vehicle control. We used a taskbattery that measured lateral and longitudinal
      vehicle control in both simulated and real world driving. Important parameters
      are magnification factor (compared to unity, a magnification of 0.5 leads to a
      lower course stability and overestimation of speed and distance) and FOV
      (increasing the FOV from 50 degrees to 100 degrees improves performance in
      lateral control tasks). However, the positive effects of a doubled FOV cannot
      outweigh the negative effects of magnification 0.5, when both factors are
      confounded. Less critical is the image resolution (lowering the image resolution
      leads to distance overestimation and degraded longitudinal control) and image
      update rate (rates below 5 - 10 Hz decrease lateral control). Camera viewpoint
      (i.e., the location of the camera) is not critical for vehicle control. Overall,
      we can conclude that vehicle control with an indirect viewing system is
      proficient when the image parameters are adequately chosen. This supports the
      further development of these kind of driver support systems.

PMID- 14668171
TI  - In-vehicle vibration study of child safety seats.
AB  - This paper reports experimental measurements of the in-vehicle vibrational
      behaviour of stage 0&1 child safety seats. Road tests were performed for eight
      combinations of child, child seat and automobile. Four accelerometers were
      installed in the vehicles and orientated to measure as closely as possible in the
      vertical direction; two were attached to the floor and two located at the human
      interfaces. An SAE pad was placed under the ischial tuberosities of the driver at
      the seat cushion and a child pad, designed for the purpose of this study, was
      placed under the child. Four test runs were made over a pave' (cobblestone)
      surface for the driver's seat and four for the child seat at both 20 km h(-1) and
      40 km h(-1). Power spectral densities were determined for all measurement points
      and acceleration transmissibility functions (ATFs) were estimated from the floor
      of the vehicle to the human interfaces. The system composed of automobile seat,
      child seat and child was found to transmit greater vibration than the system
      composed of automobile seat and driver. The ensemble mean transmissibility in the
      frequency range from 1 to 60 Hz was found to be 77% for the child seats systems
      as opposed to 61% for the driver's seats. The acceleration transmissibility for
      the child seat system was found to be higher than that of the driver's seat at
      most frequencies above 10 Hz for all eight systems tested. The measured ATFs
      suggest that the principal whole-body vibration resonance of the children
      occurred at a mean frequency of 8.5, rather than the 3.5 to 5.0 Hz typically
      found in the case of seated adults. It can be concluded that current belt
      fastened child seats are less effective than the vehicle primary seating systems
      in attenuating vibrational disturbances. The results also suggest the potential
      inability of evaluating child comfort by means of existing whole-body vibration
      standards.

PMID- 14668172
TI  - Effect of caffeine on target detection and rifle marksmanship.
AB  - Thirteen healthy and rifle-trained male military reservists performed shooting
      sessions on two separate occasions 1 h following the ingestion of placebo or 300
      mg of caffeine. Shooting included both friend-foe (FF) and vigilance (VIG) tasks,
      and were performed in the following order: two FF sequences (4 min each), four
      VIG sequences (30 min each), and two additional FF sequences. The shooting
      sessions lasted approximately 2.5 h under outdoor conditions (air temperature
      range from - 3 to 14 degrees C) and were held 48 h apart in a counter-balanced
      order. Performance measures during the shooting session included engagement time,
      friend-foe discrimination, and marksmanship accuracy and precision. Assessments
      of thermal comfort, tiredness, and debilitating symptoms preceded and followed
      the shooting session, while a self-assessment on performance was administered
      post-shooting only. Blood was sampled immediately prior to the beginning of the
      shooting session and was used to determine plasma caffeine, cortisol, and
      testosterone levels. Engagement times were faster and certain measures of
      accuracy and precision were impaired during the later FF and VIG sequences.
      However, caffeine ingestion had no affect upon any of the marksmanship measures,
      although it did alleviate cold stress and tiredness. That caffeine ingestion did
      not affect target detection and rifle marksmanship is a finding that differs from
      other studies, and is explained by a beneficial arousal caused by the mild level
      of cold stress experienced by the participants.

PMID- 14668173
TI  - Measurement and prediction of single and multi-digit finger strength.
AB  - Hand and finger strength has direct application in the design of human-machine
      interfaces involving the whole hand or single digits. Limited finger strength
      data is available, however, particularly for practical situations such as
      pinching and poking. A study was conducted in which strength in a variety of
      couplings was collected from 100 participants, in order to enhance and supplement
      the existing literature. Differences between couplings, gender, and age groups
      were evaluated. Strength was significantly higher for multi-digit couplings as
      compared with single digit couplings (p < 0.05). In addition, female strength was
      approximately 70% of male strength across all couplings. No significant
      differences were found between three age groups ranging from 18 to 40 + years
      old. Multiple regression models were used to determine whether finger strength
      could be predicted from other strength measures and anthropometry. Regression
      results suggest that finger strength can be predicted with only moderate accuracy
      using these variables (R2-adj: 0.45 - 0.64; standard error: 12 - 19 N). Such
      models are easy to implement, however, and begin to overcome the limitations of
      direct finger strength measurements.

PMID- 14668174
TI  - Traffic sign symbol comprehension: a cross-cultural study.
AB  - The objective of this study was to evaluate the comprehension levels of highway
      traffic sign symbols used in different countries, to identify underlying rules
      that affect comprehension levels, and recommend approaches to deal with the
      problem. The need for such an evaluation was based on today's travel culture
      where people are often licensed in one country and then drive--without any
      further training--in another country. We compared the comprehension levels of
      different traffic sign symbols in four countries with moderate to high levels of
      motorization: Canada, Finland, Israel, and Poland. Five different driver
      populations were sampled in each country: novice drivers, college students,
      tourists, problem drivers, and older drivers. There were large differences in
      comprehension among specific sign messages, different countries, and different
      driver populations. Signs were comprehended best when they were consistent with
      general ergonomic guidelines for display design as they relate to spatial
      compatibility, conceptual compatibility, physical representation, familiarity,
      and standardization. Illustrations of compliance with these principles and
      violations of these principles are presented, and their implication for traffic
      safety are discussed. Specific recommendations for sign design that is compliant
      with ergonomic principles, and for greater international cooperation in sign
      symbol design are made.

PMID- 14668175
TI  - A study on the student pilot's mental workload due to personality types of both
      instructor and student.
AB  - The main purpose of this paper is to provide the ideal flight crew combination
      for instructor and student pilots in order to enhance the flight training effects
      based on Myers Briggs Type Indicator (MBTI) theory. In addition to personality,
      various levels of flight difficulty are considered in order to investigate their
      potential interaction effect in terms of student pilots' mental workload measured
      in heart rate, altitude deviation, NASA-TLX (Task Load Index) and subjective
      degree of personality harmony. Based on an experiment performed in a real flight
      situation, we found significant effects of personality combinations in terms of
      all four outcome measures. Both group C types of instructors and students who are
      concrete, realistic and have mechanical skills turn out to be the ideal flight
      crew combination. A structural equation model, fitted to analyse causality among
      the four response variables, implied that as the heart rate increased, the
      altitude deviation increased. In addition, as the altitude deviation and
      personality harmony increased, NASA-TLX increased. The results of this study are
      expected to provide a theoretical basis for manning the flight crew combinations
      and thereby enhancing the efficiency of flight training.

PMID- 14668176
TI  - No interference of task complexity with circadian rhythmicity in a constant
      routine protocol.
AB  - Time course in task performance has been studied extensively. In particular, the
      investigation of circadian rhythmicity in task performance that varied in
      complexity. However, these studies disclosed heterogeneous outcomes. This could
      be the result of confounding exogenous factors, the use of diverse tasks, as well
      as accumulating sleepiness interfering with the underlying circadian drive. The
      present study varied task demands systematically within a single task and a dual
      task, using a constant routine protocol to examine the unmasked influence of the
      endogenous circadian oscillator on the periodicity of performance. Moreover, the
      subjects were divided into an early-start and a late-start group to estimate the
      potential interaction of circadian rhythmicity with the duration of prior
      wakefulness. The results revealed a distinct congruence in the circadian rhythms
      of all performance measures, with which prior wakefulness (< 40 h) did not
      interact. Also, single-task as well as dual-task complexity did not interfere
      with circadian rhythmicity. In conclusion, when sufficiently controlled for
      masking exogenous factors, task complexity is removed from the underlying
      circadian rhythms.

PMID- 14668178
TI  - Cardioversion of persistent atrial fibrillation--not yet an outdated treatment.

PMID- 14668179
TI  - Predicting the risk of atrial fibrillation after coronary artery bypass surgery.
AB  - Atrial fibrillation (AF) is the most common arrhythmia, with an incidence of 17
      33%, after coronary artery bypass grafting (CABG) and it increases the cost of
      operative treatment. beta-Blocker therapy reduces markedly the incidence of
      postoperative AF. The more effective preventive methods, e.g. amiodarone therapy
      or atrial pacing, are not cost-effective for all the patients. Thus,
      identification of patients at high risk of AF after CABG would be helpful. This
      review summarizes the predictors of postoperative AF and the current methods for
      risk stratification. In summary, identification of the patients at high risk of
      postoperative AF remains a challenge. The clinical usefulness of most of the
      conventional factors, e.g. age or history of AF, is low. Even attempts to build
      logistic regression models based on the pre- and intraoperative variables have
      failed to provide powerful predictors for postoperative AF after CABG. From the
      new predictors, the P-wave duration in signal-averaged ECG looks promising.
      Sensitivity and negative predictive value are high, positive predictive value
      remains low, which limits its usefulness. Contrary, even detailed analysis of
      standard 12-lead ECG or measure of heart rate variability has failed to provide
      useful information for risk stratification. A new method for risk stratification
      has been developed in our centre. The diagnostic accuracy of high-rate atrial
      pacing seems to be sufficient to identify a group of patients to whom
      prophylactic treatment could be proactively targeted. Further experience is,
      however, warranted to verify significance of this method in everyday clinical
      practice.

PMID- 14668180
TI  - Results from clinical trials on ST-elevation myocardial infarction in a historic
      perspective with some pathophysiological aspects.
AB  - OBJECTIVE: Since the publication of the large trials on streptokinase and aspirin
      improving mortality related to an acute ST-elevation myocardial infarction
      (STEMI) there has been numerous studies on improving treatment results with new
      fibrinolytics, adjuvant heparin therapy and primary percutaneous intervention
      (PCI). The aim of the present overview is, in a historic perspective, to link
      some of the pathophysiology of mechanisms related to plaque rupture and following
      thrombosis to the effects of drug combinations and PCI observed in major clinical
      trials conducted in patients with STEMI. DESIGN: The overview comprises short
      analyses of the initial streptokinase trials (GISSI-1 and ISIS-2), the
      comparisons between streptokinase and tissue plasminogen activator (rt-PA) and
      the role of adjuvant heparin treatment (GISSI-2, ISIS-3, GUSTO I). Also included
      is the comparison between the new bolus-teplases and traditional, accelerated
      infusion of rt-PA (GUSTO III and ASSENT-2) and between unfractionated heparin
      (UFH) and low molecular weight heparin (LWMH) given in addition to tenecteplase
      (ASSENT-3). The pathophysiology of the antiplatelet and antithrombin effects is
      described, in order to elucidate the treatment differences observed in the
      trials. In addition, the role of primary PCI is discussed in view of the results
      in a recent meta-analysis of controlled comparisons with fibrinolytic therapy.
      RESULTS: Based upon these trials it seems that the optimal thrombolytic treatment
      is a combination of a bolus-teplase (tenecteplae) and LMWH given on top of
      aspirin. Primary PCI may be the most optimal treatment, provided given early
      following STEMI (<1 h), but whether PCI is the best alternative for all patients
      with STEMI is still a matter of debate. CONCLUSION: During the last 15 years the
      optimal antithrombotic treatment of STEMI has developed from a combination of
      streptokinase and aspirin to the new bolus-teplases combined with LMWH and
      aspirin. The use of primary PCI may be a better alternative than fibrinolytic
      therapy, but such a statement needs confirmation in a large comparison between
      PCI and a quick infusion of modern fibrinolytic agents.

PMID- 14668181
TI  - Poor maintenance of sinus rhythm after electrical cardioversion of patients with
      atrial fibrillation or flutter: a 5-year follow-up of 268 consecutive patients.
AB  - OBJECTIVE: To report long-term results of direct current (DC)-cardioversion in
      unselected patients with atrial fibrillation (AF) or flutter. DESIGN: The study
      was a retrospective 5-year follow-up of all patients undergoing DC-cardioversion
      for AF or flutter at our institution between 1993 and 1997. RESULTS: Three
      hundred and eighty-five DC-cardioversions were performed in 268 patients. Two
      hundred and forty-nine patients underwent cardioversion for the first time. Of
      these, 183 (74%) were converted to sinus rhythm. During the first month of follow
      up 105 (57%) relapsed into AF. Only 33 patients (13%) of the 249 patients
      scheduled for cardioversion remained in sinus rhythm after 1 year. In
      multivariate analysis arrhythmia duration was the only variable that was
      associated with successful cardioversion. Periprocedural complications occurred
      in 9.9% of the cardioversions. CONCLUSION: In daily routine only a minority of
      patients will maintain sinus rhythm after DC-cardioversion for AF or flutter.
      Also, DC-cardioversion is not without risk. These observational data suggest a
      conservative approach to re-establishment of sinus rhythm in patients with AF.

PMID- 14668182
TI  - Global dispersion of right atrial repolarization in healthy pigs and patients.
AB  - OBJECTIVE: To investigate the feasibility of monophasic action potential (MAP)
      mapping using an electroanatomical mapping system (CARTO) in obtaining
      information on global dispersion of atrial repolarization and to evaluate the
      role of dispersion of repolarization in the genesis of paroxysmal atrial
      fibrillation (PAF). METHODS AND RESULTS: Right atrial MAPs were recorded from 53
      +/- 18 sites in 10 healthy pigs and 33 +/- 21 sites in 6 patients with and 4
      patients without history of PAF. In pigs, the global dispersions of activation
      time (AT), MAP duration and end of repolarization time (EOR), 70 +/- 8, 95 +/- 18
      and 121 +/- 28 ms, respectively, were significantly greater than those among 10,
      20 and 30 sites. In patients with PAF, the global dispersions of MAP duration and
      EOR (128 +/- 10 and 149 +/- 31 ms) were significantly greater than those in
      patients without PAF (84 +/- 10 and 91 +/- 17 ms). CONCLUSION: MAP mapping using
      the CARTO system was feasible in experimental and clinical settings in obtaining
      information on global dispersion of atrial repolarization. The number of
      recording sites could significantly affect repolarization parameters. The
      dispersions of atrial repolarization were significantly greater in patients with
      PAF than those without, suggesting the involvement of an increased dispersion of
      repolarization in the genesis of PAF.

PMID- 14668183
TI  - Recent unstable angina and off-pump coronary artery bypass grafting is not
      related to postoperative atrial fibrillation.
AB  - OBJECTIVE: Atrial fibrillation (AF) is the most frequently encountered
      postoperative arrhythmic complication after coronary artery bypass grafting
      (CABG). The purpose of the present study was to investigate the incidence and
      predictors of postoperative AF in patients with stable and unstable angina
      pectoris undergoing on-pump and off-pump CABG procedures. DESIGN: One hundred and
      seventeen stable, unstable on-pump and off-pump CABG patients were included in
      the present study. Holter data were collected 1 day before the operation to the
      2nd postoperative day. AF was registered as positive if any AF event occurred.
      RESULTS: The overall incidence of postoperative AF and sustained AF was 31.6 and
      25.6%, respectively. Postoperative AF incidences in stable on-pump, unstable on
      pump and stable off-pump patients were 29.5, 39.0 and 25%, respectively (p =
      0.412). Patients with AF had compromised postoperative haemodynamic function,
      greater need of inotropic support and antiarrhythmic medication, and longer
      intensive care unit (ICU) stays. CONCLUSION: Post-CABG AF is associated with more
      complicated postoperative outcome. Recent unstable angina and off-pump procedure
      is not related to the occurrence of post-CABG AF.

PMID- 14668184
TI  - Electroanatomic mapping of transseptal conduction during coronary sinus pacing in
      patients with paroxysmal atrial fibrillation.
AB  - OBJECTIVE: To delineate the electrophysiological properties of transseptal
      conduction from the left to the right atrium in patients with paroxysmal atrial
      fibrillation (AF). DESIGN AND RESULTS: Right atrial mapping using the
      electroanatomic mapping technique was performed at 111 +/- 16 sites in 16
      patients with paroxysmal AF during pacing from distal coronary sinus (CS). A
      single transseptal breakthrough near the CS ostium was observed in all patients.
      The activation time from the pacing site to the earliest septal activation site
      was 47 +/- 13 ms. The total septal activation time (68 +/- 16 ms) was markedly
      longer but the total right atrial activation time (118 +/- 17 ms) was similar to
      that in patients without AF in a previous observation. CONCLUSION: During distal
      CS pacing, a preferential site of transseptal conduction near the CS ostium was
      demonstrated in patients with paroxysmal AF. This has clinical implications when
      surgical dissection or catheter ablation is considered to eliminate interatrial
      connection in patients with AF.

PMID- 14668185
TI  - Prediction of atrial fibrillation in patients with severe mitral stenosis--role
      of atrial contribution to ventricular filling.
AB  - OBJECTIVE: Atrial contribution to ventricular filling was studied to assess its
      role in predicting the future development of atrial fibrillation (AF) in patients
      with severe mitral stenosis (MS) and sinus rhythm. DESIGN: Two hundred and eight
      patients with severe MS and sinus rhythm were followed up for 1 year. Baseline
      data were compared between group I (who developed AF at follow-up) and group II
      (who maintained sinus rhythm). Left atrial size, severity of MS, velocity time
      integral (VTI) of mitral valve flow and VTI due to atrial systole (A-VTI) were
      noted. Percentage contribution of A-VTI to the total VTI (A-%) was calculated.
      Sensitivity and specificity of A-% to predict the onset of AF was obtained.
      RESULTS: Left atrial size, severity of MS and total VTI were similar in the two
      groups. Group I patients were older (31.1 +/- 9.1 and 18.4 +/- 6.5 years,
      respectively, p < 0.03) with smaller A-VTI (5.3 +/- 2.2 and 6.7 +/- 3.4 cm,
      respectively, p < 0.01) and A-% (8.9 +/- 1.8 and 11.2 +/- 2.7, respectively, p <
      0.003). A-% of <9% (mean value of A-VTI in group I) had high sensitivity (84%,
      positive predictive value 76%) and specificity (80%, negative predictive value
      87%) to predict the development of AF. CONCLUSION: Atrial contribution to
      ventricular filling is reduced in patients prone to develop AF (due to
      inefficient left atrial contraction, much before its dilatation). It can be used
      for early identification of patients likely to develop AF with high sensitivity
      and specificity. It is simple, easily available, cost-effective and will guide
      earlier intervention and more frequent follow-up. There is a preclinical loss in
      atrial pump function much before the eventual onset of AF.

PMID- 14668186
TI  - N-acetylcysteine as an additive to crystalloid cardioplegia increased oxidative
      stress capacity in CABG patients.
AB  - OBJECTIVE: This prospective, randomized study was designed to assess the effects
      of N-acetylcysteine (NAC) in coronary artery bypass graft (CABG) patients.
      DESIGN: Thirty-five consenting CABG patients with normal myocardial function were
      randomly divided into control (C) patients (N = 20) who received crystalloid
      (Plegisol) cardioplegia, and NAC patients receiving NAC in a 0.04 mol/l solution
      (N = 15) in Plegisol. Simultaneous coronary sinus and aortic blood samples, and
      myocardial biopsies were taken 1, 5 and 10 min after declamping. Hemodynamics was
      measured invasively for 24 h. RESULTS: There were no adverse effects observed.
      The myocardial glutathione content was significantly better preserved (p =
      0.0001) and myeloperoxidase activity was over two times lower in the NAC group
      than in the C group (p = 0.03). The trap capacity gradient between the aorta and
      the coronary sinus increased significantly during the first minute of reperfusion
      in the treatment group (p = 0.001) when compared with the C group. In the first
      minute after reperfusion there were more leukocytes sequestered in the coronary
      circulation (p = 0.04) in the C group. The invasive hemodynamic data did not
      differ significantly between the groups. The incidence of arrhythmias was equal.
      CONCLUSION: NAC increased tissue capacity against oxidative stress and decreased
      inflammatory response in CABG patients with normal ejection fraction.

PMID- 14668187
TI  - Comparison of the centrifugal and roller pump in elective coronary artery bypass
      surgery--a prospective, randomized study with special emphasis upon platelet
      activation.
AB  - Objective--Evaluation of the centrifugal pump vs roller pump concerning effects
      upon platelet function, hemolysis and clinical outcome in elective coronary
      artery bypass surgery. Design--Thirty-four patients were randomized to
      centrifugal or roller pump. Platelet activation was studied by flow cytometry
      before, during and up to 3 days after bypass. Results--Duration of bypass,
      ischemic period, peripheral anastomoses, hospital stay and mortality did not
      differ. In roller pump patients, platelet aggregates increased by 250% between
      end of bypass and 3 h postoperatively (p < 0.001). A secondary, fivefold increase
      in number of platelet aggregates was found on the 3rd postoperative day (p <
      0.001). In the centrifugal pump group, these changes were not significant.
      Hemolysis increased (20%) at end of bypass and 3 h postoperatively (p < 0.005),
      and decreased to preoperative levels the next day without group difference.
      Conclusion--Platelet aggregation was significantly increased in roller compared
      with centrifugal pump patients, indicating higher susceptibility to postoperative
      thrombotic complications with the roller pump. Otherwise, there was no clinical
      evidence for superiority of the centrifugal pump.

PMID- 14668188
TI  - The immediate effects of deep breathing exercises on atelectasis and oxygenation
      after cardiac surgery.
AB  - Objective--To investigate the effects of deep breathing performed on the second
      postoperative day after coronary artery bypass graft surgery. Design--The
      immediate effects of 30 deep breaths performed without a mechanical device (n =
      21), with a blow bottle device (n = 20) and with an inspiratory resistance
      positive expiratory pressure mask (n = 20) were studied. Spiral computed
      tomography and arterial blood gas analyses were performed immediately before and
      after the intervention. Results--Deep breathing caused a significant decrease in
      atelectatic area from 12.3 +/- 7.3% to 10.2 +/- 6.7% (p < 0.0001) of total lung
      area 1 cm above the diaphragm and from 3.9 +/- 3.5% to 3.3 +/- 3.1% (p < 0.05) 5
      cm above the diaphragm. No difference between the breathing techniques was found.
      The aerated lung area increased by 5% (p < 0.001). The PaO (2) increased by 0.2
      kPa (p < 0.05), while PaCO (2) was unchanged in the three groups. Conclusion--A
      significant decrease of atelectatic area, increase in aerated lung area and a
      small increase in PaO (2) were found after performance of 30 deep breaths. No
      difference between the three breathing techniques was found.

PMID- 14668196
TI  - Neuroinformatics in model organisms.

PMID- 14668197
TI  - Expression analysis of the lingerer gene in the larval central nervous system of
      Drosophila melanogaster.
AB  - The lingerer (lig) gene is necessary for initiation and termination of copulatory
      behavior in Drosophila melanogaster. The lig gene encodes cytoplasmic proteins,
      and is expressed in the central nervous system (CNS) during the late third-instar
      larval stage when the lig function is required for normal copulation to occur
      after adult eclosion. To characterize the lig-expressing cells in the late third
      instar larval CNS, we have isolated a genomic fragment containing the
      promoter/enhancer region of the lig gene, and established transgenic lines in
      which expression of reporter genes is controlled by the lig promoter/enhancer. In
      the larval brain, reporter genes were expressed in all of the glial cells and in
      clusters of neurons that projected contralaterally. In the larval ventral
      ganglion, reporter genes were expressed in subperineurial glia, peripheral exit
      glia, and a number of interneurons, but not in motor neurons. In the cloned
      promoter/enhancer region, we have found the sequence motif for binding of the
      REPO protein, a transcription factor essential for the differentiation and
      maintenance of glial cells. The lig gene is thus one of the candidate target
      genes for the REPO transcription factor.

PMID- 14668198
TI  - Cell-specific expression of the lark RNA-binding protein in Drosophila results in
      morphological and circadian behavioral phenotypes.
AB  - Past studies have implicated the Drosophila LARK protein in the circadian control
      of adult eclosion behavior. LARK has a broad tissue pattern of distribution, and
      is pan-neuronal in the differentiated brain. In certain peptidergic neurons, LARK
      abundance changes in a circadian manner. However, the precise cellular
      requirement for LARK, with respect to circadian behavior, is still not known. To
      explore this issue, we employed the GAL4/UAS binary expression system to increase
      LARK abundance in defined neuronal cell types. Interestingly, LARK expression in
      Crustacean Cardioactive Peptide (CCAP) neurons caused an early-eclosion
      phenotype, whereas a similar perturbation in the Eclosion Hormone (EH) cells
      resulted in abnormally late peaks of eclosion. Surprisingly, LARK expression in
      Pigment Dispersing Factor (PDF)- or TIMELESS (TIM)-containing clock neurons
      caused behavioral arrhythmicity, even though clock protein cycling was found to
      be normal in these flies. Although the observed effects of LARK expression
      mirrored those seen with genetic ablation of the relevant peptidergic
      populations, there was no evidence of defective cell development or morphology.
      This suggests that an alteration of cell function rather than cell death is the
      cause of the aberrant phenotypes. Diminished PDF immunoreactivity in flies
      expressing LARK in the PDF neurons suggests that an effect on neuropeptide
      synthesis, transport, or release may contribute to the observed arrhythmicity.
      Importantly, the expression of LARK in several other cell populations did not
      have detectable effects on development, viability or behavior, indicating a
      specificity of action within certain cell types.

PMID- 14668199
TI  - Effects of combining a cryptochrome mutation with other visual-system variants on
      entrainment of locomotor and adult-emergence rhythms in Drosophila.
AB  - "For every behavioral observation, there is an equal and opposite observation."
      S. Benzer Photoreception is an important component of rhythm systems and is
      involved in adjusting circadian clocks to photic features of daily cycles. In
      Drosophila, it has been suggested that there are three light input pathways to
      the clock that underlie rhythms of adult behavior: One involves the eyes; the
      other two extraocular photoreception through a structure called the Hofbauer
      Buchner (H-B) eyelet and light reception carried out by pacemaker neurons
      themselves, mediated by a substance called cryptochrome. All photoreceptor cells
      including the H-B eyelet have been surmised to be removed by glass-null
      mutations. Mutations in the no-receptor-potential-A (norpA) gene cause the
      compound eyes and ocelli to be non-functional and may also affect the eyelet's
      function. The one cryptochrome mutant known (cryb) harbors an amino-acid
      substitution in the blue-light absorbing protein encoded by this gene. With
      regard to adult locomotor rhythms, all single mutants (gl60j, norpAP41, and cryb)
      re-entrained to altered light:dark (LD) cycles in which the L phase involved
      relatively intense light. Dropping light levels ca. 10 or ca. 30-fold permitted
      small percentages of doubly-mutant gl60j cryb flies clearly to re-synchronize
      their behavior. The marginal re-entrainability in the lowest-light situation
      nevertheless involved superior responsiveness of the gl60j cryb type, compared
      with that observed previously using a different re-entrainment protocol.
      Furthermore, transgenic types in which rhodopsin-expressing cells within the H-B
      eyelet were ablated or suffered from the effects of tetanus-toxin also entrained
      with behavior similar or superior to that of gl60j cryb at a low light level.
      Light inputs that are necessary to synchronize periodic adult emergence can be
      inferred (from previous studies) to involve a cry-dependent pathway and perhaps
      also a norpA-dependent one, so that combining mutations in these two genes would
      cause cultures to be unentrainable. The current results were that each singly
      mutant type eclosed rhythmically; flies emerging from norpAP41;cryb cultures also
      (on balance) exhibited solid eclosion rhythmicity. The ensemble of these
      behavioral and adult-emergence results suggest that additional light-to-clock
      pathways function within the system; alternatively, that rhythm assays employed
      here have teased out residual function of the mutated CRY protein.

PMID- 14668200
TI  - Prevalence of the fragile X syndrome in Yugoslav patients with non-specific
      mental retardation.
AB  - Mutations at two fragile sites, FRAXA and FRAXE, loci are caused by an expansion
      of a CGG/GCC trinucleotide repeat and are characterized by mental retardation.
      Here we report molecular screening survey of 97 unrelated individuals diagnosed
      with non-specific mental retardation (MR), which produced positive test for FRAXA
      in two boys and none positive for the FRAXE mutation. In addition, we studied
      allelic frequency distribution for the FRAXA locus in this group of mentally
      retarded patients, as well as in the 99 healthy subjects of Yugoslav population.
      The distribution of FMR1 CGG repeat size in both groups was similar: the most
      common allele contained 29 repeats (32.86% in the healthy population and 54.54%
      in MR population), followed by the allele with 28 CGG repeats (21.43% in the
      healthy and 12.2% in MR population). Premutation alleles with more than 45
      repeats were not found in control nor in the MR group.

PMID- 14668201
TI  - Association analysis of 5-HTTLPR variants, 5-HT2a receptor gene 102T/C
      polymorphism and migraine.
AB  - It is well known that migraine has a strong genetic component, although the type
      and number of genes involved is not yet clear. There is evidence to suggest that
      serotonin-related genes participate in the pathogenesis of migraine. Previous
      studies have shown that gender differences influence the serotonergic
      neurotransmission and, in addition, the migraine prevalence is higher in females
      than males. Therefore, we investigated the functional polymorphism in the
      upstream regulatory region of the serotonin transporter gene (5-HTTLPR) and the
      102T/C polymorphism of the 5-HT2A receptor gene in the Hungarian female
      population. These genes were analysed in 126 migraine sufferers (with or without
      aura)and 101 unrelated healthy controls using case control design. A borderline
      association (chi2 = 3.84, df = 1, p = 0.049; OR = 1.45, 95% CI = 1.00-2.12)
      between 5-HTTLPR short (S) allele and migraine was found. No significant
      difference between migraine sufferers and controls was observed for the 102T/C
      polymorphism of 5-HT2A receptor gene. Furthermore, there was no significant
      interaction between5-HTTLPR and 102T/C polymorphisms in our study population. In
      conclusion, our results support that the genetic susceptibility of migraine may
      be associated with a locus at or near the 5-HT transporter gene.

PMID- 14668202
TI  - Dose-response study of intrafollicular injection of insulin-like growth factor-I
      on follicular fluid factors and follicle dominance in mares.
AB  - The effect of insulin-like growth factor-I (IGF-I) on the concentrations of
      follicular fluid factors during follicle deviation and the development of
      dominance was studied in mares in two experiments. Transvaginal ultrasound
      guidance was used for intrafollicular injection and subsequent sequential
      sampling of follicular fluid. Treatment involved a single injection of IGF-I into
      the second-largest follicle (F2) at the expected beginning of deviation (Hour 0)
      based on diameter (> or =20 mm) of the largest follicle (F1). Mares in IGF-I
      groups were given a dose of 500 microg (experiment 1) or 250, 25, or 2.5 microg
      (experiment 2). Ablation of F1 at Hour 24 was done in experiment 1, but not in
      experiment 2. The 500- and 250-microg doses stimulated growth, leading to
      ovulation of F2 in 10 of 10 and 4 of 5 mares in the two experiments,
      respectively, compared to 4 of 12 and 0 of 5 in saline-injected controls. These
      doses prevented (P < 0.05) the increase in IGF binding protein-2 and
      androstenedione that occurred in F2 of controls and increased (P < 0.05) the
      concentrations of activin-A, inhibin-A, and vascular endothelial growth factor
      (VEGF). The 500-microg dose stimulated higher (P < 0.05) concentrations of
      estradiol, but not until Hour 48, whereas the lower doses were ineffective. In
      experiment 2, free IGF-I concentrations in F2 at Hour 24 decreased progressively
      as the dose decreased so that concentrations for the 2.5-microg dose were higher
      (P < 0.05) than in F2 of controls and similar (not significantly different) to
      endogenous concentrations in F1. Correspondingly, concentrations of
      androstenedione in F2 at Hour 24 were lower (P < 0.05) and concentrations of
      activin-A, inhibin-A, and VEGF were higher (P < 0.05) after treatment of F2 with
      the 2.5-microg dose than in F2 of controls and were similar to concentrations in
      F1. Hence, a physiologic intrafollicular dose of IGF-I did not stimulate
      estradiol production but reduced the production of androstenedione and stimulated
      the production of activin-A, inhibin-A, and VEGF during follicle selection in
      mares.

PMID- 14668203
TI  - Regulation of luteinizing hormone/human chorionic gonadotropin receptor
      expression: a perspective.
AB  - The LH/hCG receptor, a member of the G protein coupled receptor family mediates
      the cellular actions of LH in the ovary. A considerable amount of information
      regarding its structure, mechanism of activation, and regulation of expression
      has emerged in recent years. Here we provide a brief overview of the current
      information on the structural organization of the receptor and the mechanism of
      receptor mediated signaling as well as an in-depth discussion on recent
      developments pertaining to the regulation of receptor expression. Specifically,
      we describe studies from our laboratory showing that the posttranscriptional
      regulation of the receptor involves an LH/hCG receptor mRNA-binding protein. We
      also propose a model to explain the loss of steady-state LH/hCG receptor mRNA
      levels during receptor down-regulation.

PMID- 14668204
TI  - Adamts-1 is essential for the development and function of the urogenital system.
AB  - Successful ovulation and implantation processes play a crucial role in female
      fertility. Adamts-1, a matrix metalloproteinase with disintegrin and
      thrombospondin motifs, has been suggested to be regulated by the progesterone
      receptor in the hormonal pathway leading to ovulation. With the primary aim of
      investigating the role of Adamts-1 in female fertility, we generated Adamts-1
      null mice. Forty-five percent of the newborn Adamts-1 null mice die, with death
      most likely caused by a kidney malformation that becomes apparent at birth.
      Surviving female null mice were subfertile, whereas males reproduced normally.
      Ovulation in null females was impaired because of mature oocytes remaining
      trapped in ovarian follicles. No uterine phenotype was apparent in Adamts-1 null
      animals. Embryo implantation occurred normally, the uteri were capable of
      undergoing decidualization, and no morphological changes were observed. These
      results demonstrate that a functional Adamts-1 is required for normal ovulation
      to occur, and hence the Adamts-1 gene plays an important role in female
      fertility, primarily during the tissue remodeling process of ovulation.

PMID- 14668205
TI  - Cloning and localization of three forms of gonadotropin-releasing hormone,
      including the novel whitefish form, in a salmonid, Coregonus clupeaformis.
AB  - Cells containing different GnRH peptides currently are thought to have distinct
      locations and functions in the brain. Lake whitefish is the first salmonid
      species to have three forms of GnRH peptide in contrast to later-evolving
      salmonids (salmon and trout) in which only two forms have been identified. Our
      objective was to isolate the cDNAs that code for these transcripts and to
      localize the transcripts for the three forms of GnRH in adult lake whitefish
      brain. Also, we provide phylogenetic analysis of these three whitefish genes
      based on their preprohormone sequence. From whitefish we isolated cDNAs encoding
      chicken (c)GnRH-II, salmon (s)GnRH, and the novel whitefish (wf)GnRH. The three
      cDNAs each encode only one GnRH and are placed in separate groups with
      phylogenetic analysis. A combination of in situ hybridization and
      immunocytochemistry with two antisera revealed neurons that expressed protein
      and/or mRNA for cGnRH-II in the midbrain and hindbrain; sGnRH in the olfactory
      nerve and bulb, ventral telencephalon, and preoptic area; and wfGnRH in the same
      latter two brain regions and the hypothalamus. Thus, in the anterior brain, cells
      containing sGnRH and wfGnRH were in the same brain areas but not at identical
      locations in the ventral telencephalon and preoptic area. Based on our results,
      we speculate that both sGnRH and wfGnRH have gonadotropin-releasing roles in the
      lake whitefish brain.

PMID- 14668206
TI  - Membrane type 1-matrix metalloproteinase (MMP)-associated MMP-2 activation
      increases in the rat ovary in response to an ovulatory dose of human chorionic
      gonadotropin.
AB  - Gonadotropins stimulate ovarian proteolytic enzyme activity that is believed to
      be important for the remodeling of the follicular extracellular matrix. Membrane
      type 1-matrix metalloproteinase (MT1-MMP) has been identified in vitro as an
      activator of pro-MMP-2 by forming a complex with tissue inhibitors of
      metalloproteinase-2 (TIMP-2). In the present study, the expression pattern of MT1
      MMP mRNA and the role of MT1-MMP were examined in the ovary using the
      gonadotropin-treated immature rat model. Ovaries were collected at selected times
      after eCG or hCG. RNase protection assays revealed a transient increase in MT1
      MMP mRNA beginning 4 h after hCG. High expression of MT1-MMP mRNA was localized
      to the theca-interstitial layer of developing and preovulatory follicles, while
      low expression was observed in the granulosa cell layer of developing follicles
      by in situ hybridization. The localization pattern of MT1-MMP mRNA was compared
      with TIMP-2 mRNA. Both MMP-2 and TIMP-2 mRNA were expressed in the theca layer of
      preovulatory follicles, showing a similarity to MT1-MMP mRNA expression. To
      further determine whether MT1-MMP activates pro-MMP-2 in the ovary, crude plasma
      membrane fractions from preovulatory ovaries were analyzed by gelatin zymography.
      In plasma membrane fractions, pro-MMP-2 increased around the time of ovulation.
      Upon incubation, pro-MMP-2 was activated with the highest levels of activation at
      12 h post-hCG. The addition of MT1-MMP antibody or excess TIMP-2 to membrane
      fractions inhibited pro-MMP-2 activation. The increase in MT1-MMP mRNA may be an
      important part of the mechanism necessary for the efficient generation of active
      MMP-2 during the ovulatory process.

PMID- 14668207
TI  - Testicular expression and distribution of the rat bcl2 modifying factor in
      response to reduced intratesticular testosterone.
AB  - The Bcl2 modifying factor (Bmf) is a pro-apoptotic member of the Bcl2 family of
      apoptosis-related proteins that has been shown to initiate apoptosis in response
      to the loss of attachment of cells from their basal lamina (anoikis).
      Experimental reduction in intratesticular testosterone concentration brings about
      the death of spermatids as a consequence of their sloughing from Sertoli cells.
      Given the role of Bmf in anoikis in other systems, we hypothesized that Bmf would
      be expressed in germ cells and that its expression and normal distribution might
      be altered under conditions that induce widespread germ cell loss. To test these
      hypotheses, we demonstrated that Bmf indeed is expressed in the testis and cloned
      the full-length rat Bmf cDNA. Immunohistochemistry revealed that Bmf is present
      in the subacrosomal space of postmeiotic spermatids from step 4 to 16 of
      spermiogenesis. To test the hypothesis that Bmf expression and distribution are
      altered by conditions that elicit anoikis, intratesticular testosterone was
      reduced by implanting Silastic capsules containing testosterone and estradiol
      into adult rats for 8 weeks. As hypothesized, this resulted in a significant
      change in Bmf distribution relative to untreated animals. In particular, Bmf
      exhibited a loss of its normal subacrosomal distribution, becoming redistributed
      throughout the cytoplasm and nucleus, and appeared in cells in which it is not
      normally expressed (e.g., pachytene spermatocytes). Additionally, Bmf mRNA
      expression increased in response to lowered testosterone. These results suggest
      that Bmf may well be involved in germ cell apoptosis and/or anoikis in response
      to decreased intratesticular testosterone concentration.

PMID- 14668208
TI  - Expression and localization of hypoxia-inducible factor-1 subunits in the adult
      rat epididymis.
AB  - The epididymal epithelium contributes to formation of a luminal fluid that is
      essential for the protection of spermatozoa from a variety of insults including
      changes in oxygen tension. A key regulator of the response to oxygen debt in many
      cells is hypoxia-inducible factor-1 (HIF-1). A transcription factor composed of
      alpha and beta subunits, HIF-1 activates genes that mediate oxygen homeostasis
      and cell survival pathways or trigger cell death responses. Previously we have
      shown that HIF-1alpha mRNA is expressed in the adult rat epididymis. Goals of
      this study were to determine whether HIF-1alpha protein is activated by ischemia
      in the rat epididymis, to determine whether epididymal HIF-1alpha mRNA expression
      is androgen dependent, and to identify epididymal cell types expressing HIF
      1alpha and beta. Immunoblot analysis revealed that HIF-1alpha protein is
      primarily present in corpus and cauda of the normoxic epididymis and unaffected
      by ischemia, whereas HIF-1beta was detected equally in all regions and also
      unaffected by ischemia. HIF-1alpha mRNA expression in all regions was not
      affected by 15 days bilateral orchiectomy. Principal cells stained positive for
      HIF-1alpha by immunocytochemistry, with the epithelium of initial segment and
      caput epididymidis staining less intensely than corpus and cauda. HIF-1beta
      immunoreactivity was equally present in principal cells in all regions. Clear,
      narrow, and basal cells were unreactive for HIF-1alpha and beta. The presence of
      HIF-1 in normoxic epididymis and the regional distribution of HIF-1alpha suggests
      fundamental differences in how proximal and distal regions of the epididymis
      maintain oxygen homeostasis to protect the epithelium and spermatozoa from
      hypoxia.

PMID- 14668209
TI  - Female sex steroid hormones and pregnancy regulate receptors for calcitonin gene
      related peptide in rat mesenteric arteries, but not in aorta.
AB  - Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide known
      to be involved in the regulation of vascular tone. Results of previous studies
      from our laboratory and others suggest that vascular sensitivity to CGRP is
      enhanced during pregnancy and that the female sex steroid hormones estradiol
      17beta (E2) and progesterone (P4) may be involved in this process. We
      hypothesized that CGRP receptors in the mesenteric artery are increased during
      pregnancy and with sex steroid hormone treatments. In the present study, we
      investigated whether pregnancy and female sex steroid hormones modulate the CGRP
      receptors CGRP-A and CGRP-B in the mesenteric artery in the rat. The CGRP-A
      receptor consists of calcitonin receptor-like receptor (CRLR) and receptor
      activity-modifying protein 1 (RAMP1); however, the CGRP-B receptor needs to be
      further characterized. Messenger RNA levels for CRLR and RAMP1 were assessed by
      reverse transcription-polymerase chain reaction, and CGRP-B receptor proteins
      levels were determined by Western blot analysis. In addition, [125I]CGRP binding
      was measured by Scatchard analysis. Both mRNA for CGRP-A (CRLR and RAMP1) and the
      protein for CGRP-B receptors in mesenteric arteries were increased with pregnancy
      compared to nonpregnant, diestrous animals. A P4 antagonist, RU-486,
      downregulated and P4 upregulated these receptors in mesenteric arteries (P <
      0.05) in pregnant rats. In adult ovariectomized rats, P4 upregulated CRLR and
      RAMP1 mRNA levels as well as [125I]CGRP-binding sites. The CGRP-B-receptor
      protein levels were significantly (P < 0.05) elevated by P4 and by combined E2
      and P4 treatment. Together with earlier findings, these data suggest that
      increases in the expression of CGRP-A (CRLR and RAMP1) and CGRP-B receptors in
      mesenteric arteries may be important in reducing vascular resistance and in
      vascular adaptations that occur during pregnancy; in addition, P4 may be involved
      in this process.

PMID- 14668210
TI  - Analysis of imprinted messenger RNA expression during bovine preimplantation
      development.
AB  - While the expression and epigenetic differences of imprinted genes have been
      extensively characterized in the mouse and human, little is known about imprinted
      genes in livestock species. In the current study, eight genes that are imprinted
      in the human or mouse were investigated in preimplantation bovine embryos.
      Amplified cDNA was created from three single metaphase II (MII) oocytes or
      embryos throughout preimplantation development. The imprinted genes Dlk1 and Mest
      (isoform 1) had no detectable transcripts during preimplantation development.
      Gnas and Grb10 were expressed in most embryos from the 2-cell to blastocyst
      stages of development. Mest (isoform 2) was expressed in all oocytes and embryos,
      except for one blastocyst sample. Ndn and Xist were expressed from the 8-16-cell
      stage (maternal-to-zygotic transition, MZT) onwards. Sgce was expressed until the
      MZT, and Nnat in both early (alpha form) and late (beta form) stage embryos. The
      paternally imprinted genes Gnas, Grb10, and Xist were expressed in both in vitro
      fertilized (IVF) and parthenogenetically activated (PA) blastocysts as expected.
      Of the four maternally imprinted genes expressed in the blastocyst (Mest, Ndn,
      Nnat, and Sgce), Nnat alone showed differential mRNA expression between IVF and
      PA blastocysts, suggesting imprinting by this stage of development. In
      conclusion, seven of the eight genes investigated showed mRNA expression during
      preimplantation development, indicating a potential role during early
      development. Also significant is the observation that Nnat is imprinted by the
      blastocyst stage of development although the other genes are not, indicating a
      temporal imprinting program.

PMID- 14668211
TI  - Expression and regulation of lipocalin-type prostaglandin d synthase in rat
      testis and epididymis.
AB  - Lipocalin-type prostaglandin D synthase (L-PGDS), a bifunctional protein, is
      expressed in the male reproductive organs of many species. However, the
      expression and regulation of L-PGDS in rat are still uncertain. The present study
      investigated the regionalization and regulation of L-PGDS expression in rat
      testis and epididymis by in situ hybridization and immunohistochemistry under the
      conditions of sexual maturation, castration, and ethylene dimethane sulfonate
      (EDS) treatments. In sexually mature rats, L-PGDS mRNA was weakly expressed only
      in the testicular peritubular cells, whereas L-PGDS immunostaining was highly
      detected in the Leydig cells by Day 70 postpartum. During sexual maturation, L
      PGDS mRNA expression was highly detected in the caput, corpus, and cauda of the
      epididymis 70 days after birth. Compared with normal L-PGDS expression in adult
      epididymis, both L-PGDS mRNA expression and protein immunostaining were
      significantly reduced in the caput, corpus, and cauda epididymis after
      castration. Testosterone propionate treatment induced a significant increase of L
      PGDS expression in the epididymis of castrated rats. Compared with adult rat
      epididymis, L-PGDS mRNA and protein expression was down-regulated after EDS
      treatment. Testosterone propionate treatment could induce an increase of L-PGDS
      mRNA and protein expression in the epididymis of EDS-treated rats. In conclusion,
      both castration and EDS treatments caused a significant decrease of L-PGDS
      expression in the epididymis, whereas testosterone propionate treatment could
      induce an increase of L-PGDS expression in the epididymis of both castrated and
      EDS-treated rats, indicating that L-PGDS expression in the rat epididymis can be
      up-regulated by testosterone.

PMID- 14668212
TI  - Circadian regulation of gonadotropin-releasing hormone neurons and the
      preovulatory surge in luteinizing hormone in the diurnal rodent, Arvicanthis
      niloticus, and in a nocturnal rodent, Rattus norvegicus.
AB  - Daily rhythms in the timing of the preovulatory surge and the display of
      reproductive behavior are reversed in diurnal and nocturnal rodents, but little
      is known about the neural mechanisms underlying these differences. We examined
      this issue by comparing a diurnal murid rodent, Arvicanthis niloticus (the grass
      rat), to a nocturnal one, Rattus norvegicus (the lab rat). In the first study, we
      established that sequential estradiol and progesterone treatment induces a
      proestrous-like rise in LH secretion and in the percentage of GnRH neurons that
      express Fos in grass rats, as is the case in lab rats. Next, we tested the
      hypothesis that differences in the timing of estrus-related events in diurnal and
      nocturnal species are caused by differences in rhythms in responsiveness to
      steroid hormones. We found rhythms in GnRH neuron activity, as indicated by Fos,
      that were 12 hours out of phase in grass rats and lab rats. These patterns
      persisted in both species when animals were housed in constant darkness for 5
      days, suggesting that they are driven by an endogenous circadian mechanism. These
      results indicate that steroid-primed grass rats and lab rats are similar with
      respect to the temporal relationship among estrus-related events, but that the
      timing of these events relative to the light-dark cycle is dramatically different
      and that this difference is caused by endogenous circadian mechanisms.

PMID- 14668213
TI  - Proteolytic degradation of insulin-like growth factor binding proteins by ovarian
      follicles: a control mechanism for selection of dominant follicles.
AB  - This review summarizes evidence for the role of proteolytic enzymes that degrade
      and inactivate insulin-like growth factor binding proteins (IGFBP) during
      follicular development in mammals. In some species (e.g., bovine), evidence
      indicates that decreases in IGFBP-4 and -5 levels in estrogen-dominant
      preovulatory follicles are likely due, in part, to increased protease activity,
      whereas lower levels of IGFBP-2 are not due to increased proteolysis. Increased
      IGFBP-4 and -5 protease along with lower amounts of IGFBP-4 binding activity and
      greater amounts of free IGF-I are some of the earliest developmental changes
      documented in bovine growing antral follicles. This protease activity has
      recently been ascribed to serine metalloprotease(s), including pregnancy
      associated plasma protein-A (PAPP-A), which was first detected in human
      follicular fluid nearly 20 yr ago. Other recent studies verified the presence of
      PAPP-A mRNA in granulosa cells of humans, monkeys, cattle, mice, and pigs.
      Increases in the amount of PAPP-A mRNA in granulosa cells during follicular
      development occurs in some but not all species, indicating that other proteases
      or protease inhibitors may be involved in IGFBP degradation. Whether the hormonal
      control of PAPP-A production/activity by the ovary differs between monotocous and
      polytocous animals will require further study. These protease-induced decreases
      in IGFBP-4 and -5 likely cause increased levels of bioavailable (or free) IGFs
      that stimulate steroidogenesis and mitogenesis in developing dominant follicles,
      which ultimately prepare the follicle(s) and oocyte(s) for successful ovulation
      and fertilization.

PMID- 14668214
TI  - Effects of chilling on structural aspects of early preantral mouse follicles.
AB  - Chilling injury is one of the major limiting factors for achieving optimal
      cryopreservation of gametes. This study aimed to determine potential chilling
      induced damage on several structural aspects of early preantral mouse follicles.
      Mechanically isolated intact early preantral follicles (type 3b-4) were exposed
      to 0 degrees C for 1, 5, 10, or 30 min. Control and chilled follicles were
      analyzed by confocal microscopy after staining for tubulin, F-actin, and
      chromatin, and by electron microscopy. Chilling for only 1 min was sufficient to
      cause depolymerization of microtubules in the oocyte and the surrounding
      granulosa cell layer as evidenced by a substantial decrease in fluorescence
      intensity after antitubulin labeling. Cooling for longer periods caused
      alterations in microtubule organization in the follicle-enclosed oocyte. These
      alterations included the loss of interphase microtubules, concomitant with the
      formation of perinuclear or cortical microtubule asters and sometimes a complete
      disappearance of microtubules. The extent of microtubule modification was related
      to the time of chilling, but was fully reversible after rewarming follicles at 37
      degrees C for 1 h. Chilling had only minor effects on the actin-containing
      elements located predominantly in the oocyte cortex and the transzonal
      projections. Ultrastructural analysis confirmed that oocyte-somatic cell
      interactions were present. There was no influence on the chromatin configuration
      within the follicle-enclosed oocyte. These results indicate that mouse follicles
      are relatively tolerant to direct chilling injury and, as a consequence, are able
      to withstand the cooling-warming steps during conventional cryopreservation
      procedures.

PMID- 14668215
TI  - Expression and role of the ether-a-go-go-related (MERG1A) potassium-channel
      protein during preimplantation mouse development.
AB  - Potassium channels play important roles in many cellular processes, including
      cell-cycle progression and cell differentiation. In the present study, we
      investigated the pattern of expression of the mouse ether-a-go-go-related (KCNH2;
      MERG1A) potassium channel during mouse embryogenic development. Analysis by
      reverse transcription-polymerase chain reaction revealed maternal MERG1A
      transcripts until the late 2-cell stage of development, after which MERG1A
      expression from the zygotic genome was low until the 8-cell stage, then rose in
      the morula, but was low in trophoblast compared to inner cell mass cells. A
      trophoblast stem cell line also was shown to express MERG1A mRNA. Immunoblotting
      of oocytes, blastocysts, and the trophoblast stem cell line revealed different
      posttranslationally processed forms of MERG1A. Immunofluorescence analysis showed
      that the subcellular localization of MERG1A varied at different stages of the
      embryogenic cell cycle. In addition, MERG1A protein levels increased following
      compaction at the 8-cell stage, and its distribution became polarized. This
      relocalization of MERG1A was affected by treatment with specific inhibitors of
      ether-a-go-go-related gene (ERG)-channel function and of actin polymerization.
      Puromycin treatment of morulae indicated that membrane-associated MERG1A had a
      half-life of greater than 24 h. The ERG-specific inhibitor E-4031 reduced the
      incidence of blastocyst formation and the number of cells per blastocyst. These
      results show that MERG1A is developmentally regulated and suggest that it might
      play a role in early mouse embryogenic development.

PMID- 14668216
TI  - Combining DNA expression with positional information to detect functional
      silencing of chromosomal regions.
AB  - MOTIVATION: Loss of chromosomal material is often observed in cancer cells. In
      this situation the expression of genes is related to their position on the
      genome. Epigenetic phenomena may also silence several genes in the same region of
      a chromosome. While cytogenetic or other molecular genetic methods spot changes
      of DNA copy number, they cannot detect other causes of silencing. RESULTS: We
      propose a method that utilizes the link from expression information gained from
      high-density DNA microarrays to the gene locus according to current databases.
      Statistical methods adequate to spot conspicuous runs of non-expressed genes are
      introduced and compared to one another by merit of their power and robustness
      against false positives. AVAILABILITY: Code for the formulae can be obtained (R
      code) via http://www.panix.com/~derwisch/hannes/longrun

PMID- 14668218
TI  - JXP4BIGI: a generalized, Java XML-based approach for biological information
      gathering and integration.
AB  - MOTIVATION: In the post-genomic era, biologists interested in systems biology
      often need to import data from public databases and construct their own system
      specific or subject-oriented databases to support their complex analysis and
      knowledge discovery. To facilitate the analysis and data processing, customized
      and centralized databases are often created by extracting and integrating
      heterogeneous data retrieved from public databases. A generalized methodology for
      accessing, extracting, transforming and integrating the heterogeneous data is
      needed. RESULTS: This paper presents a new data integration approach named
      JXP4BIGI (Java XML Page for Biological Information Gathering and Integration).
      The approach provides a system-independent framework, which generalizes and
      streamlines the steps of accessing, extracting, transforming and integrating the
      data retrieved from heterogeneous data sources to build a customized data
      warehouse. It allows the data integrator of a biological database to define the
      desired bio-entities in XML templates (or Java XML pages), and use embedded
      extended SQL statements to extract structured, semi-structured and unstructured
      data from public databases. By running the templates in the JXP4BIGI framework
      and using a number of generalized wrappers, the required data from public
      databases can be efficiently extracted and integrated to construct the bio
      entities in the XML format without having to hard-code the extraction logics for
      different data sources. The constructed XML bio-entities can then be imported
      into either a relational database system or a native XML database system to build
      a biological data warehouse. AVAILABILITY: JXP4BIGI has been integrated and
      tested in conjunction with the IKBAR system (http://www.ikbar.org/) in two
      integration efforts to collect and integrate data for about 200 human genes
      related to cell death from HUGO, Ensembl, and SWISS-PROT (Bairoch and Apweiler,
      2000), and about 700 Drosophila genes from FlyBase (FlyBase Consortium, 2002).
      The integrated data has been used in comparative genomic analysis of x-ray
      induced cell death. Also, as explained later, JXP4BIGI is a middleware and
      framework to be integrated with biological database applications, and cannot run
      as a stand-alone software for end users. For demonstration purposes, a
      demonstration version is accessible at (http://www.ikbar.org/jxp4bigi/demo.html).

PMID- 14668217
TI  - Annotation pattern of ESTs from Spodoptera frugiperda Sf9 cells and analysis of
      the ribosomal protein genes reveal insect-specific features and unexpectedly low
      codon usage bias.
AB  - MOTIVATION: A whole set of Expressed Sequence Tags (ESTs) from the Sf9 cell line
      of Spodoptera frugiperda is presented here for the first time. By this way we
      want to identify both conserved and specific genes of this pest species. We also
      expect from this analysis to find a class of protein sequences providing a tool
      to explore genomic features and phylogeny of Lepidoptera. RESULTS: The ESTs
      display both housekeeping as well as developmentally regulated genes, and a high
      percentage of sequences with unknown function. Among the identified ORFs, almost
      all ribosomal proteins (RPs) were found with high EST redundancy and hence
      sequence accuracy. The codon usage found among RP genes is in average
      surprisingly much less biased in Lepidoptera than in other organisms. Other
      Spodoptera genes also displayed a low bias, suggesting a general genome
      expression feature in this Lepidoptera. We also found that the L35A and L36 RP
      sequences, respectively, display 40 and 10 amino-acid insertions, both being
      present only in insects. Sequence analysis suggests that they are probably not
      subjected to a strong selective pressure and may be good phylogenetic markers for
      Lepidoptera. Most interestingly, the Lepidoptera sequences of 9 RP genes
      displayed a specific signature different from the canonical one. We conclude that
      the RP family allows valuable comparative genomics and phylogeny of Lepidoptera.
      AVAILABILITY: All EST sequence data are available from the private 'Spodo-Base'
      upon request.

PMID- 14668219
TI  - Efficient estimation of emission probabilities in profile hidden Markov models.
AB  - MOTIVATION: Profile hidden Markov models provide a sensitive method for
      performing sequence database search and aligning multiple sequences. One of the
      drawbacks of the hidden Markov model is that the conserved amino acids are not
      emphasized, but signal and noise are treated equally. For this reason, the number
      of estimated emission parameters is often enormous. Focusing the analysis on
      conserved residues only should increase the accuracy of sequence database search.
      RESULTS: We address this issue with a new method for efficient emission
      probability (EEP) estimation, in which amino acids are divided into effective and
      ineffective residues at each conserved alignment position. A practical study with
      20 protein families demonstrated that the EEP method is capable of detecting
      family members from other proteins with sensitivity of 98% and specificity of 99%
      on the average, even if the number of free emission parameters was decreased to
      15% of the original. In the database search for TIM barrel sequences, EEP
      recognizes the family members nearly as accurately as HMMER or Blast, but the
      number of false positive sequences was significantly less than that obtained with
      the other methods. AVAILABILITY: The algorithms written in C language are
      available on request from the authors.

PMID- 14668220
TI  - Combining phylogenetic data with co-regulated genes to identify regulatory
      motifs.
AB  - MOTIVATION: Discovery of regulatory motifs in unaligned DNA sequences remains a
      fundamental problem in computational biology. Two categories of algorithms have
      been developed to identify common motifs from a set of DNA sequences. The first
      can be called a 'multiple genes, single species' approach. It proposes that a
      degenerate motif is embedded in some or all of the otherwise unrelated input
      sequences and tries to describe a consensus motif and identify its occurrences.
      It is often used for co-regulated genes identified through experimental
      approaches. The second approach can be called 'single gene, multiple species'. It
      requires orthologous input sequences and tries to identify unusually well
      conserved regions by phylogenetic footprinting. Both approaches perform well, but
      each has some limitations. It is tempting to combine the knowledge of co
      regulation among different genes and conservation among orthologous genes to
      improve our ability to identify motifs. RESULTS: Based on the Consensus algorithm
      previously established by our group, we introduce a new algorithm called PhyloCon
      (Phylogenetic Consensus) that takes into account both conservation among
      orthologous genes and co-regulation of genes within a species. This algorithm
      first aligns conserved regions of orthologous sequences into multiple sequence
      alignments, or profiles, then compares profiles representing non-orthologous
      sequences. Motifs emerge as common regions in these profiles. Here we present a
      novel statistic to compare profiles of DNA sequences and a greedy approach to
      search for common subprofiles. We demonstrate that PhyloCon performs well on both
      synthetic and biological data. AVAILABILITY: Software available upon request from
      the authors. http://ural.wustl.edu/softwares.html

PMID- 14668221
TI  - Scoring clustering solutions by their biological relevance.
AB  - MOTIVATION: A central step in the analysis of gene expression data is the
      identification of groups of genes that exhibit similar expression patterns.
      Clustering gene expression data into homogeneous groups was shown to be
      instrumental in functional annotation, tissue classification, regulatory motif
      identification, and other applications. Although there is a rich literature on
      clustering algorithms for gene expression analysis, very few works addressed the
      systematic comparison and evaluation of clustering results. Typically, different
      clustering algorithms yield different clustering solutions on the same data, and
      there is no agreed upon guideline for choosing among them. RESULTS: We developed
      a novel statistically based method for assessing a clustering solution according
      to prior biological knowledge. Our method can be used to compare different
      clustering solutions or to optimize the parameters of a clustering algorithm. The
      method is based on projecting vectors of biological attributes of the clustered
      elements onto the real line, such that the ratio of between-groups and within
      group variance estimators is maximized. The projected data are then scored using
      a non-parametric analysis of variance test, and the score's confidence is
      evaluated. We validate our approach using simulated data and show that our
      scoring method outperforms several extant methods, including the separation to
      homogeneity ratio and the silhouette measure. We apply our method to evaluate
      results of several clustering methods on yeast cell-cycle gene expression data.
      AVAILABILITY: The software is available from the authors upon request.

PMID- 14668222
TI  - Classification of protein quaternary structure with support vector machine.
AB  - MOTIVATION: Since the gap between sharply increasing known sequences and slow
      accumulation of known structures is becoming large, an automatic classification
      process based on the primary sequences and known three-dimensional structure
      becomes indispensable. The classification of protein quaternary structure based
      on the primary sequences can provide some useful information for the biologists.
      So a fully automatic and reliable classification system is needed. This work
      tries to look for the effective methods of extracting attribute and the algorithm
      for classifying the quaternary structure from the primary sequences. RESULTS:
      Both of the support vector machine (SVM) and the covariant discriminant
      algorithms have been first introduced to predict quaternary structure properties
      from the protein primary sequences. The amino acid composition and the auto
      correlation functions based on the amino acid index profile of the primary
      sequence have been taken into account in the algorithms. We have analyzed 472
      amino acid indices and selected the four amino acid indices as the examples,
      which have the best performance. Thus the five attribute parameter data sets
      (COMP, FASG, NISK, WOLS and KYTJ) were established from the protein primary
      sequences. The COMP attribute data set is composed of amino acid composition, and
      the FASG, NISK, WOLS and KYTJ attribute data sets are composed of the amino acid
      composition and the auto-correlation functions of the corresponding amino acid
      residue index. The overall accuracies of SVM are 78.5, 87.5, 83.2, 81.7 and
      81.9%, respectively, for COMP, FASG, NISK, WOLS and KYTJ data sets in jackknife
      test, which are 19.6, 7.8, 15.5, 13.1 and 15.8%, respectively, higher than that
      of the covariant discriminant algorithm in the same test. The results show that
      SVM may be applied to discriminate between the primary sequences of homodimers
      and non-homodimers and the two protein sequence descriptors can reflect the
      quaternary structure information. Compared with previous Robert Garian's
      investigation, the performance of SVM is almost equal to that of the Decision
      tree models, and the methods of extracting feature vector from the primary
      sequences are superior to Robert's binning function method. AVAILABILITY:
      Programs are available on request from the authors.

PMID- 14668224
TI  - caCORE: a common infrastructure for cancer informatics.
AB  - MOTIVATION: Sites with substantive bioinformatics operations are challenged to
      build data processing and delivery infrastructure that provides reliable access
      and enables data integration. Locally generated data must be processed and stored
      such that relationships to external data sources can be presented. Consistency
      and comparability across data sets requires annotation with controlled
      vocabularies and, further, metadata standards for data representation.
      Programmatic access to the processed data should be supported to ensure the
      maximum possible value is extracted. Confronted with these challenges at the
      National Cancer Institute Center for Bioinformatics, we decided to develop a
      robust infrastructure for data management and integration that supports advanced
      biomedical applications. RESULTS: We have developed an interconnected set of
      software and services called caCORE. Enterprise Vocabulary Services (EVS) provide
      controlled vocabulary, dictionary and thesaurus services. The Cancer Data
      Standards Repository (caDSR) provides a metadata registry for common data
      elements. Cancer Bioinformatics Infrastructure Objects (caBIO) implements an
      object-oriented model of the biomedical domain and provides Java, Simple Object
      Access Protocol and HTTP-XML application programming interfaces. caCORE has been
      used to develop scientific applications that bring together data from distinct
      genomic and clinical science sources. AVAILABILITY: caCORE downloads and web
      interfaces can be accessed from links on the caCORE web site
      (http://ncicb.nci.nih.gov/core). caBIO software is distributed under an open
      source license that permits unrestricted academic and commercial use. Vocabulary
      and metadata content in the EVS and caDSR, respectively, is similarly
      unrestricted, and is available through web applications and FTP downloads.
      SUPPLEMENTARY INFORMATION: http://ncicb.nci.nih.gov/core/publications contains
      links to the caBIO 1.0 class diagram and the caCORE 1.0 Technical Guide, which
      provide detailed information on the present caCORE architecture, data sources and
      APIs. Updated information appears on a regular basis on the caCORE web site
      (http://ncicb.nci.nih.gov/core).

PMID- 14668223
TI  - Algorithms for large-scale genotyping microarrays.
AB  - MOTIVATION: Analysis of many thousands of single nucleotide polymorphisms (SNPs)
      across whole genome is crucial to efficiently map disease genes and understanding
      susceptibility to diseases, drug efficacy and side effects for different
      populations and individuals. High density oligonucleotide microarrays provide the
      possibility for such analysis with reasonable cost. Such analysis requires
      accurate, reliable methods for feature extraction, classification, statistical
      modeling and filtering. RESULTS: We propose the modified partitioning around
      medoids as a classification method for relative allele signals. We use the
      average silhouette width, separation and other quantities as quality measures for
      genotyping classification. We form robust statistical models based on the
      classification results and use these models to make genotype calls and calculate
      quality measures of calls. We apply our algorithms to several different
      genotyping microarrays. We use reference types, informative Mendelian
      relationship in families, and leave-one-out cross validation to verify our
      results. The concordance rates with the single base extension reference types are
      99.36% for the SNPs on autosomes and 99.64% for the SNPs on sex chromosomes. The
      concordance of the leave-one-out test is over 99.5% and is 99.9% higher for AA,
      AB and BB cells. We also provide a method to determine the gender of a sample
      based on the heterozygous call rate of SNPs on the X chromosome. See
      http://www.affymetrix.com for further information. The microarray data will also
      be available from the Affymetrix web site. AVAILABILITY: The algorithms will be
      available commercially in the Affymetrix software package.

PMID- 14668225
TI  - Global snapshot of a protein interaction network-a percolation based approach.
AB  - MOTIVATION: Biologically significant information can be revealed by modeling
      large-scale protein interaction data using graph theory based network analysis
      techniques. However, the methods that are currently being used draw conclusions
      about the global features of the network from local connectivity data. A more
      systematic approach would be to define global quantities that measure (1) how
      strongly a protein ties with the other parts of the network and (2) how
      significantly an interaction contributes to the integrity of the network, and
      connect them with phenotype data from other sources. In this paper, we introduce
      such global connectivity measures and develop a stochastic algorithm based upon
      percolation in random graphs to compute them. RESULTS: We show that, in terms of
      global connectivities, the distribution of essential proteins is distinct from
      the background. This observation highlights a fundamental difference between the
      essential and the non-essential proteins in the network. We also find that the
      interaction data obtained from different experimental methods such as
      immunoprecipitation and two-hybrid techniques contribute differently to network
      integrities. Such difference between different experimental methods can provide
      insight into the systematic bias present among these techniques. SUPPLEMENTARY
      INFORMATION: The full list of our results can be found in the supplemental web
      site
      http://www.nas.nasa.gov/Groups/SciTech/nano/msamanta/projects/percolation/index.p
      p

PMID- 14668226
TI  - SEMEDA: ontology based semantic integration of biological databases.
AB  - MOTIVATION: Many molecular biological databases are implemented on relational
      Database Management Systems, which provide standard interfaces like JDBC and ODBC
      for data and metadata exchange. By using these interfaces, many technical
      problems of database integration vanish and issues related to semantics remain,
      e.g. the use of different terms for the same things, different names for
      equivalent database attributes and missing links between relevant entries in
      different databases. RESULTS: In this publication, principles and methods that
      were used to implement SEMEDA (Semantic Meta Database) are described. Database
      owners can use SEMEDA to provide semantically integrated access to their
      databases as well as to collaboratively edit and maintain ontologies and
      controlled vocabularies. Biologists can use SEMEDA to query the integrated
      databases in real time without having to know the structure or any technical
      details of the underlying databases. AVAILABILITY: SEMEDA is available at
      http://www-bm.ipk-gatersleben.de/semeda/. Database providers who intend to grant
      access to their databases via SEMEDA are encouraged to contact the authors.

PMID- 14668227
TI  - Susceptibility of non-linear systems as an approach to metabolic responses.
AB  - MOTIVATION: Recent developments of several analytical techniques and fast
      sampling procedures are making it possible to study non-linear dynamics on an
      automated basis. Approaches that suggest experimental setups and fully exploit
      the data are needed. To prevent unreliable fits of parameters to experimental
      data, model-independent methods would be advantageous. One such method consists
      in representing the response of a system by means of a transformation or
      functional, of an excitation, i.e. a flux of a metabolite. RESULTS: A functional
      of unknown form can be expanded in series if its functional derivatives are
      known. An algorithm for calculating such generalized derivatives from impulse
      perturbation experiments was developed. The only assumption was that the implicit
      kinetics is time-independent, i.e. the system is time-invariant. The method is
      illustrated on a part of fructose catabolism. A reaction network that involves 14
      metabolites and 11 enzymes and includes several branches and feedback loops is
      considered. It is shown that the method provides good approximations to the
      responses of this complex system. AVAILABILITY: FUNDER is available from
      http://bbm1.ucm.es/torralba/funder/down/ SUPPLEMENTARY INFORMATION:
      http://bbm1.ucm.es/torralba/funder/

PMID- 14668228
TI  - Metabolic pathways in three dimensions.
AB  - MOTIVATION: Currently a substantial research effort is devoted to automated
      representation of metabolic and gene networks. Automatic visualization plays a
      significant role in such efforts, and becomes an important problem on its own.
      Graphical visualization of metabolic pathways has to be information dense and not
      'overloaded', recognizable and unified, close to traditional and algebraically
      consistent. The use of three-dimensional 'virtual reality' visualizations may
      help to understand better the intricate topology of metabolic and regulatory
      networks. RESULTS: A system of visualizing metabolic networks as graphs in three
      dimensional space by means of Virtual Reality Modeling Language (VRML) is
      presented. The system is based on an XML-compliant MNV ('Metabolic Network
      Visualizer') language, and comprises MNV language standard and parser, MNV to
      VRML translator, and interactive pathway constructor, all unified by the HTML
      graphic user interface. AVAILABILITY: The MNV can be accessed in viewer mode at
      http://www.patronov.net/sciencevr/mnv/indexview.html or in constructor mode at
      http://www.patronov.net/sciencevr/mnv/indexmake.html SUPPLEMENTARY INFORMATION:
      The figures for the paper as well as the Appendices may be found at
      http://www.patronov.net/sciencevr/mnv/screenshots.html

PMID- 14668229
TI  - Accelerating screening of 3D protein data with a graph theoretical approach.
AB  - MOTIVATION: The Dictionary of Interfaces in Proteins (DIP) is a database
      collecting the 3D structure of interacting parts of proteins that are called
      patches. It serves as a repository, in which patches similar to given query
      patches can be found. The computation of the similarity of two patches is time
      consuming and traversing the entire DIP requires some hours. In this work we
      address the question of how the patches similar to a given query can be
      identified by scanning only a small part of DIP. The answer to this question
      requires the investigation of the distribution of the similarity of patches.
      RESULTS: The score values describing the similarity of two patches can roughly be
      divided into three ranges that correspond to different levels of spatial
      similarity. Interestingly, the two iso-score lines separating the three classes
      can be determined by two different approaches. Applying a concept of the theory
      of random graphs reveals significant structural properties of the data in DIP.
      These can be used to accelerate scanning the DIP for patches similar to a given
      query. Searches for very similar patches could be accelerated by a factor of more
      than 25. Patches with a medium similarity could be found 10 times faster than by
      brute-force search.

PMID- 14668230
TI  - A random variance model for detection of differential gene expression in small
      microarray experiments.
AB  - MOTIVATION: Microarray techniques provide a valuable way of characterizing the
      molecular nature of disease. Unfortunately expense and limited specimen
      availability often lead to studies with small sample sizes. This makes accurate
      estimation of variability difficult, since variance estimates made on a gene by
      gene basis will have few degrees of freedom, and the assumption that all genes
      share equal variance is unlikely to be true. RESULTS: We propose a model by which
      the within gene variances are drawn from an inverse gamma distribution, whose
      parameters are estimated across all genes. This results in a test statistic that
      is a minor variation of those used in standard linear models. We demonstrate that
      the model assumptions are valid on experimental data, and that the model has more
      power than standard tests to pick up large changes in expression, while not
      increasing the rate of false positives. AVAILABILITY: This method is incorporated
      into BRB-ArrayTools version 3.0 (http://linus.nci.nih.gov/BRB-ArrayTools.html).
      SUPPLEMENTARY MATERIAL: ftp://linus.nci.nih.gov/pub/techreport/RVM_supplement.pdf

PMID- 14668231
TI  - Assessing sequence comparison methods with the average precision criterion.
AB  - MOTIVATION: Comprehensive performance assessment is important for improving
      sequence database search methods. Sensitivity, selectivity and speed are three
      major yet usually conflicting evaluation criteria. The average precision (AP)
      measure aims to combine the sensitivity and selectivity features of a search
      algorithm. It can be easily visualized and extended to analyze results from a set
      of queries. Finally, the time-AP plot can clearly show the overall performance of
      different search methods. RESULTS: Experiments are performed based on the SCOP
      database. Popular sequence comparison algorithms, namely Smith-Waterman
      (SSEARCH), FASTA, BLAST and PSI-BLAST are evaluated. We find that (1) the low
      complexity segment filtration procedure in BLAST actually harms its overall
      search quality; (2) AP scores of different search methods are approximately in
      proportion of the logarithm of search time; and (3) homologs in protein families
      with many members tend to be more obscure than those in small families. This
      measure may be helpful for developing new search algorithms and can guide
      researchers in selecting most suitable search methods. AVAILABILITY: Test sets
      and source code of this evaluation tool are available upon request.

PMID- 14668232
TI  - Using credibility intervals instead of hypothesis tests in SAGE analysis.
AB  - MOTIVATION: Statistical methods usually used to perform Serial Analysis of Gene
      Expression (SAGE) analysis are based on hypothesis testing. They answer the
      biologist's question: 'what are the genes with differential expression greater
      than r with P-value smaller than P?'. Another useful and not yet explored
      question is: 'what is the uncertainty in differential expression ratio of a
      gene?'. RESULTS: We have used Bayesian model for SAGE differential gene
      expression ratios as a more informative alternative to hypothesis tests since it
      provides credibility intervals. AVAILABILITY: The model is implemented in R
      statistical language script and is available under GNU/GLP copyleft at
      supplemental web site. SUPPLEMENTARY INFORMATION:
      http://www.ime.usp.br/~rvencio/SAGEci/

PMID- 14668233
TI  - A CART-based approach to discover emerging patterns in microarray data.
AB  - MOTIVATION: Cancer diagnosis using gene expression profiles requires supervised
      learning and gene selection methods. Of the many suggested approaches, the method
      of emerging patterns (EPs) has the particular advantage of explicitly modeling
      interactions among genes, which improves classification accuracy. However,
      finding useful (i.e. short and statistically significant) EP is typically very
      hard. METHODS: Here we introduce a CART-based approach to discover EPs in
      microarray data. The method is based on growing decision trees from which the EPs
      are extracted. This approach combines pattern search with a statistical procedure
      based on Fisher's exact test to assess the significance of each EP. Subsequently,
      sample classification based on the inferred EPs is performed using maximum
      likelihood linear discriminant analysis. RESULTS: Using simulated data as well as
      gene expression data from colon and leukemia cancer experiments we assessed the
      performance of our pattern search algorithm and classification procedure. In the
      simulations, our method recovers a large proportion of known EPs while for real
      data it is comparable in classification accuracy with three top-performing
      alternative classification algorithms. In addition, it assigns statistical
      significance to the inferred EPs and allows to rank the patterns while
      simultaneously avoiding overfit of the data. The new approach therefore provides
      a versatile and computationally fast tool for elucidating local gene interactions
      as well as for classification. AVAILABILITY: A computer program written in the
      statistical language R implementing the new approach is freely available from the
      web page http://www.stat.uni-muenchen.de/~socher/

PMID- 14668234
TI  - The MUSC DNA Microarray Database.
AB  - SUMMARY: The Medical University of South Carolina (MUSC) DNA Microarray Database
      is a web-accessible archive of DNA microarray data. The database was developed
      using the DNA microarray project/data management system, micro ArrayDB.
      Annotations for each DNA microarray project and associated cRNA target
      information are stored in a MySQL relational database and linked to array
      hybridization data (raw and normalized). At the discretion of investigators, data
      are placed into the public domain where they can be interrogated and downloaded
      through a web browser. In addition to serving as an online resource of gene
      expression data, the MUSC DNA Microarray Database is a model for other academic
      DNA microarray data repositories. AVAILABILITY: Browsing and downloading of MUSC
      DNA Microarray Database information can be done after registration at
      http://proteogenomics.musc.edu/pss/home.php.

PMID- 14668235
TI  - MREPATT: detection and analysis of exact consecutive repeats in genomic
      sequences.
AB  - We have developed a program to determine the number, length and position of exact
      consecutive repeats of short sequences in DNA fragments or whole genomes. The
      program also gives the statistical significance of results by comparing them with
      those expected for a random sequence generated according to a Markovian model.
      AVAILABILITY: MREPATT can be accessed on line at http://www.lsi.upc.es/~alggen
      under the RESEARCH and SEARCH links.

PMID- 14668236
TI  - gff2aplot: Plotting sequence comparisons.
AB  - SUMMARY: gff2aplot is a program to visualize the alignment of two sequences
      together with their annotations. Input for the program consists of single or
      multiple files in GFF-format which specify the alignment coordinates and
      annotation features of both sequences. Output is in PostScript format of any
      size. The features to be displayed are highly customizable to meet user specific
      needs. The program serves to generate print-quality images for comparative genome
      sequence analysis. AVAILABILITY: gff2aplot is freely available under the GNU
      software licence and can be downloaded from the address specified below.
      SUPPLEMENTARY INFORMATION: http://genome.imim.es/software/gfftools/GFF2APLOT.html

PMID- 14668237
TI  - MUTAGEN: multi-user tool for annotating genomes.
AB  - SUMMARY: MUTAGEN is a free prokaryotic annotation system. It offers the
      advantages of genome comparison, graphical sequence browsers, search facilities
      and open-source for user-specific adjustments. The web-interface allows several
      users to access the system from standard desktop computers. The Sulfolobus
      acidocaldarius genome, and several plasmids and viruses have so far been analysed
      and annotated using MUTAGEN. AVAILABILITY: MUTAGEN is released as open-source
      software under GPL. The code is available for download and/or contribution at
      http://dac.molbio.ku.dk/bioinformatics/MUTAGEN/

PMID- 14668238
TI  - LOX-DB-- database on lipoxygenases.
AB  - SUMMARY: Lipoxygenases are a family of enzymes involved in a variety of human
      diseases like inflammation, asthma, artherosclerosis and cancer. The
      lipoxygenases database (LOX-DB) aims to be a web accessible compendium of
      information in particular on the mammalian members of this multigene family. This
      resource includes molecular structures, reference data, tools for structural and
      computational analysis as well as links to related information maintained by
      others. The data can be retrieved by the use of various search options and
      analyzed applying publicly available visualization tools. AVAILABILITY: LOX-DB is
      available at http://www.dkfz-heidelberg.de/spec/lox-db/

PMID- 14668239
TI  - GoFigure: automated Gene Ontology annotation.
AB  - SUMMARY: We have developed a web tool to predict Gene Ontology (GO) terms. The
      tool accepts an input DNA or protein sequence, and uses BLAST to identify
      homologous sequences in GO annotated databases. A graph is returned to the user
      via email. AVAILABILITY: The tool is freely available at:
      http://udgenome.ags.udel.edu/frm_go.html/

PMID- 14668240
TI  - PRIMEX: rapid identification of oligonucleotide matches in whole genomes.
AB  - SUMMARY: PRIMEX (PRImer Match EXtractor) can detect oligonucleotide sequences in
      whole genomes, allowing for mismatches. Using a word lookup table and server
      functionality, PRIMEX accepts queries from client software and returns matches
      rapidly. We find it faster and more sensitive than currently available tools.
      AVAILABILITY: Running applications and source code have been made available at
      http://bioinformatics.cribi.unipd.it/primex

PMID- 14668241
TI  - KISS for STRAP: user extensions for a protein alignment editor.
AB  - SUMMARY: The Structural Alignment Program STRAP is a comfortable comprehensive
      editor and analyzing tool for protein alignments. A wide range of functions
      related to protein sequences and protein structures are accessible with an
      intuitive graphical interface. Recent features include mapping of mutations and
      polymorphisms onto structures and production of high quality figures for
      publication. Here we address the general problem of multi-purpose program
      packages to keep up with the rapid development of bioinformatical methods and the
      demand for specific program functions. STRAP was remade implementing a novel
      design which aims at Keeping Interfaces in STRAP Simple (KISS). KISS renders
      STRAP extendable to bio-scientists as well as to bio-informaticians. Scientists
      with basic computer skills are capable of implementing statistical methods or
      embedding existing bioinformatical tools in STRAP themselves. For bio
      informaticians STRAP may serve as an environment for rapid prototyping and
      testing of complex algorithms such as automatic alignment algorithms or
      phylogenetic methods. Further, STRAP can be applied as an interactive web applet
      to present data related to a particular protein family and as a teaching tool.
      REQUIREMENTS: JAVA-1.4 or higher. AVAILABILITY:
      http://www.charite.de/bioinf/strap/

PMID- 14668242
TI  - SNOW: standard nomenclature wizard to help searching for (bio) chemical
      standardized names.
AB  - When developing bioinformatical tools dealing with enzymatic activity, metabolism
      or enzymatic networks, the problem of the lack of a clear nomenclature for
      biochemical compounds often arises. This problem leads us to develop a small web
      based tool (SNOW, Standard NOmenclature Wizard) which may help to find
      recommended and trivial names or the correct closest spelling for a query
      compound name, if it exists. AVAILABILITY: Web-based interface available at
      http://ibb.uab.es/snow/ SUPPLEMENTARY INFORMATION:
      http://ibb.uab.es/snow/snow_moreinfo.html

PMID- 14668243
TI  - Machaon CVE: cluster validation for gene expression data.
AB  - This paper presents a cluster validation tool for gene expression data. Machaon
      CVE (Clustering and Validation Environment) system aims to partition samples or
      genes into groups characterized by similar expression patterns, and to evaluate
      the quality of the clusters obtained. AVAILABILITY: The program is freely
      available for non-profit use on request at
      http://www.cs.tcd.ie/Nadia.Bolshakova/Machaon.html SUPPLEMENTARY INFORMATION:
      http://www.cs.tcd.ie/Nadia.Bolshakova/Machaon.html

PMID- 14668244
TI  - DnaSP, DNA polymorphism analyses by the coalescent and other methods.
AB  - SUMMARY: DnaSP is a software package for the analysis of DNA polymorphism data.
      Present version introduces several new modules and features which, among other
      options allow: (1) handling big data sets (approximately 5 Mb per sequence); (2)
      conducting a large number of coalescent-based tests by Monte Carlo computer
      simulations; (3) extensive analyses of the genetic differentiation and gene flow
      among populations; (4) analysing the evolutionary pattern of preferred and
      unpreferred codons; (5) generating graphical outputs for an easy visualization of
      results. AVAILABILITY: The software package, including complete documentation and
      examples, is freely available to academic users from: http://www.ub.es/dnasp

PMID- 14668245
TI  - SPEPlip: the detection of signal peptide and lipoprotein cleavage sites.
AB  - SUMMARY: SPEPlip is a neural network-based method, trained and tested on a set of
      experimentally derived signal peptides from eukaryotes and prokaryotes. SPEPlip
      identifies the presence of sorting signals and predicts their cleavage sites. The
      accuracy in cross-validation is similar to that of other available programs: the
      rate of false positives is 4 and 6%, for prokaryotes and eukaryotes respectively
      and that of false negatives is 3% in both cases. When a set of 409 prokaryotic
      lipoproteins is predicted, SPEPlip predicts 97% of the chains in the signal
      peptide class. However, by integrating SPEPlip with a regular expression search
      utility based on the PROSITE pattern, we can successfully discriminate signal
      peptide-containing chains from lipoproteins. We propose the method for detecting
      and discriminating signal peptides containing chains and lipoproteins.
      AVAILABILITY: It can be accessed through the web page at
      http://gpcr.biocomp.unibo.it/predictors/

PMID- 14668246
TI  - ModLoop: automated modeling of loops in protein structures.
AB  - SUMMARY: ModLoop is a web server for automated modeling of loops in protein
      structures. The input is the atomic coordinates of the protein structure in the
      Protein Data Bank format, and the specification of the starting and ending
      residues of one or more segments to be modeled, containing no more than 20
      residues in total. The output is the coordinates of the non-hydrogen atoms in the
      modeled segments. A user provides the input to the server via a simple web
      interface, and receives the output by e-mail. The server relies on the loop
      modeling routine in MODELLER that predicts the loop conformations by satisfaction
      of spatial restraints, without relying on a database of known protein structures.
      For a rapid response, ModLoop runs on a cluster of Linux PC computers.
      AVAILABILITY: The server is freely accessible to academic users at
      http://salilab.org/modloop

PMID- 14668247
TI  - Characterizing gene sets with FuncAssociate.
AB  - SUMMARY: FuncAssociate is a web-based tool to help researchers use Gene Ontology
      attributes to characterize large sets of genes derived from experiment.
      Distinguishing features of FuncAssociate include the ability to handle ranked
      input lists, and a Monte Carlo simulation approach that is more appropriate to
      determine significance than other methods, such as Bonferroni or idak p-value
      correction. FuncAssociate currently supports 10 organisms (Vibrio cholerae,
      Shewanella oneidensis, Saccharomyces cerevisiae, Schizosaccharomyces pombe,
      Arabidopsis thaliana, Caenorhaebditis elegans, Drosophila melanogaster, Mus
      musculus, Rattus norvegicus and Homo sapiens). AVAILABILITY: FuncAssociate is
      freely accessible at http://llama.med.harvard.edu/Software.html. Source code (in
      Perl and C) is freely available to academic users 'as is'.

PMID- 14668248
TI  - Lymphangioleiomyomatosis: insights about, and from, a rare disease.

PMID- 14668249
TI  - Noninvasive ventilation for cardiogenic pulmonary edema: froth and bubbles?

PMID- 14668250
TI  - Pump and circumstances.

PMID- 14668251
TI  - Corticosteroids: the "terminator" of all untreatable serious pulmonary illness.

PMID- 14668252
TI  - Competing benefits of tumor necrosis factor-alpha for bacteria and for host
      defense.

PMID- 14668253
TI  - In celebration of expectoration: induced sputum indices as outcome measures in
      cystic fibrosis.

PMID- 14668254
TI  - Ventilator-induced lung injury occurs in rats, but does it occur in humans?

PMID- 14668255
TI  - Severe acute respiratory syndrome and influenza: virus incursions from southern
      China.

PMID- 14668256
TI  - Advances in critical care hepatology.

PMID- 14668257
TI  - Modafinil and sleepiness.

PMID- 14668258
TI  - Weaning failure, muscle injury, and fatigue.

PMID- 14668259
TI  - Obstructive hypopneas in children and adolescents: normal values.

PMID- 14668260
TI  - Oxidative stress decreases pHi and Na(+)/H(+) exchange and increases excitability
      of solitary complex neurons from rat brain slices.
AB  - Putative chemoreceptors in the solitary complex (SC) are sensitive to hypercapnia
      and oxidative stress. We tested the hypothesis that oxidative stress stimulates
      SC neurons by a mechanism independent of intracellular pH (pH(i)). pH(i) was
      measured by using ratiometric fluorescence imaging microscopy, utilizing either
      the pH-sensitive fluorescent dye BCECF or, during whole cell recordings, pyranine
      in SC neurons in brain stem slices from rat pups. Oxidative stress decreased
      pH(i) in 270 of 436 (62%) SC neurons tested. Chloramine-T (CT), N
      chlorosuccinimide (NCS), dihydroxyfumaric acid, and H(2)O(2) decreased pH(i) by
      0.19 +/- 0.007, 0.20 +/- 0.015, 0.15 +/- 0.013, and 0.08 +/- 0.002 pH unit,
      respectively. Hypercapnia decreased pH(i) by 0.26 +/- 0.006 pH unit (n = 95). The
      combination of hypercapnia and CT or NCS had an additive effect on pH(i), causing
      a 0.42 +/- 0.03 (n = 21) pH unit acidification. CT slowed pH(i) recovery mediated
      by Na(+)/H(+) exchange (NHE) from NH(4)Cl-induced acidification by 53% (n = 20)
      in CO(2)/HCO(3)(-)-buffered medium and by 58% (n = 10) in HEPES-buffered medium.
      CT increased firing rate in 14 of 16 SC neurons, and there was no difference in
      the firing rate response to CT with or without a corresponding change in pH(i).
      These results indicate that oxidative stress 1). decreases pH(i) in some SC
      neurons, 2). together with hypercapnia has an additive effect on pH(i), 3).
      partially inhibits NHE, and 4) directly affects excitability of CO(2)/H(+)
      chemosensitive SC neurons independently of pH(i) changes. These findings suggest
      that oxidative stress acidifies SC neurons in part by inhibiting NHE, and this
      acidification may contribute ultimately to respiratory control dysfunction.

PMID- 14668261
TI  - Colistin interactions with the mammalian urothelium.
AB  - Here we describe the effect of colistin on the barrier function of the mammalian
      urinary bladder epithelium. Addition of colistin to the mucosal solution of the
      rabbit urinary bladder epithelium (urothelium) resulted in an increase in the
      transepithelial conductance. The magnitude of the increase in transepithelial
      conductance was dependent on the membrane voltage, concentration of colistin, and
      presence of divalent cations in the bath solution. The initial site of action of
      colistin was at the apical membrane. Colistin increased the membrane conductance
      only when the apical membrane potential was cell interior negative. The more
      negative the membrane potential, the larger the conductance increase. The
      concentration dependence of the conductance increase saturated, suggesting a
      membrane binding site. Divalent cations decreased the magnitude of the
      conductance increase. This divalent cation action occurred at two sites: one in
      competition with colistin for a membrane binding site, and the other by rapidly
      blocking the induced conductance. At short exposure times, the increase in
      conductance was reversed by either removing colistin from the bath or changing
      the voltage so that the apical membrane was cell interior positive. At long
      exposure times, the increase was only partially reversible by voltage or removal
      from the bath. This finding suggests that at long exposure times, there is a
      toxic effect of colistin on the urothelium.

PMID- 14668262
TI  - A novel mouse-driven ex vivo flow chamber for the study of leukocyte and platelet
      function.
AB  - Various in vitro and in vivo techniques exist for study of the microcirculation.
      Whereas in vivo systems impress with their physiological fidelity, in vitro
      systems excel in the amount of reduction that can be achieved. Here we introduce
      the autoperfused ex vivo flow chamber designed to study murine leukocytes and
      platelets under well-defined hemodynamic conditions. In our model, the murine
      heart continuously drives the blood flow through the chamber, providing a wide
      range of physiological shear rates. We used a balance of force approach to
      quantify the prevailing forces at the chamber walls. Numerical simulations show
      the flow characteristics in the chamber based on a shear-thinning fluid model. We
      demonstrate specific rolling of wild-type leukocytes on immobilized P-selectin,
      abolished by a blocking MAb. When uncoated, the surfaces having a constant shear
      rate supported individual platelet rolling, whereas on areas showing a rapid drop
      in shear platelets interacted in previously unreported grapelike conglomerates,
      suggesting an influence of shear rate on the type of platelet interaction. In
      summary, the ex vivo chamber amounts to an external vessel connecting the
      arterial and venous systems of a live mouse. This method combines the strengths
      of existing in vivo and in vitro systems in the study of leukocyte and platelet
      function.

PMID- 14668263
TI  - Nature versus nurture in childhood obesity: a familiar old conundrum.

PMID- 14668264
TI  - Nutritional risk predictors of beta cell autoimmunity and type 1 diabetes at a
      young age.
AB  - Type 1 diabetes is an immune-mediated disease characterized by a preclinical
      prodrome during which beta cell autoimmunity proceeds at a variable rate. Large
      geographic differences and a conspicuous increase in incidence, especially among
      young children since the 1950s, and the relatively low concordance in identical
      twins are factors that favor a critical role of environmental factors in the
      etiology of this disease. Only approximately 5% or fewer subjects with HLA
      conferred genetic susceptibility to type 1 diabetes actually develop the clinical
      disease. Breastfeeding, nicotinamide, zinc, and vitamins C, D, and E have been
      reported as possibly protecting against type 1 diabetes, whereas N-nitroso
      compounds, cow milk, increased linear growth, and obesity may increase the risk.
      Thus far, only the significance of infant feeding, cow milk, and vitamin D have
      been studied in both case-control and cohort settings. The major shortcoming of
      most studies done so far is that only single dietary exposures have been assessed
      at single time points. Putative nutritional and other confounding factors have
      received little attention as have the limitations of the dietary methods used.
      There is little firm evidence of the significance of nutritional factors in the
      etiology of type 1 diabetes. The availability of good markers of preclinical type
      1 diabetes and of genetic risk have decreased the sample sizes needed and made
      longitudinal cohort studies of the assessment of children's diets feasible.

PMID- 14668265
TI  - Changes in childhood food consumption patterns: a cause for concern in light of
      increasing body weights.
AB  - Childhood obesity is currently at its highest: recent statistics show that 16% of
      children between the ages of 6 and 11 y are overweight [> or =95th percentile of
      body mass index (BMI; in kg/m(2)) for age] and that an additional 14.3% are at
      risk of becoming overweight (> or =85th percentile but < 95th percentile of BMI
      for age). As children's body weights have increased, so has their consumption of
      fast foods and soft drinks. The proportion of foods that children consumed from
      restaurants and fast food outlets increased by nearly 300% between 1977 and 1996.
      Children's soft drink consumption has also increased during those years, and now
      soft drinks provide soft drink consumers 188 kcal/d beyond the energy intake of
      nonconsumers. These changes in food intakes among children may partly explain the
      rise in childhood obesity observed in the past few years. Although the mechanism
      of appetite regulation will not be explored in this report, it is hypothesized
      that the greater energy intakes in children who consume large amounts of soft
      drinks and fast foods are not compensated for by increased physical activity or
      decreased energy intakes. Furthermore, overweight and obesity in childhood may
      predispose persons to morbidity in adulthood. Blood pressure and fasting insulin
      and cholesterol concentrations are higher in overweight children than in normal
      weight children. This review focuses on current food patterns and eating habits
      of children, in an attempt to explain their increasing BMI. In addition, a
      critical review of food service and political practices regarding food choices
      for children at school is included.

PMID- 14668266
TI  - Vitamin C and cancer chemoprevention: reappraisal.
AB  - Several studies have reported that even a moderate daily dose of supplementary
      vitamin C (200 mg) induces the formation of genotoxins from lipid hydroperoxides,
      thereby resulting in DNA damage and initiation of carcinogenesis. However, other
      reports questioned the experimental designs used and suggested that the
      chemopreventive effects of vitamin C may be linked to the inhibition of tumor
      promotion as well as to the blocking of tumor initiation. In this article, we
      discuss issues of contention and some controversies related to the potential
      chemopreventive effects of vitamin C in carcinogenesis.

PMID- 14668267
TI  - Recovery from relapse among successful weight maintainers.
AB  - BACKGROUND: Little is known about the natural history of weight change among
      persons who are successful at losing weight. OBJECTIVE: This study evaluated the
      occurrence of weight regain and recovery among 2400 persons in the National
      Weight Control Registry (NWCR) who had lost an average (+/- SD) of 32.1 +/- 17.8
      kg and had kept it off for 6.5 +/- 8.1 y. DESIGN: Participants were evaluated
      prospectively over 2 y. RESULTS: The mean reported weight change from entry into
      the NWCR to 2 y later was 3.8 +/- 7.6 kg. At year 2, 96.4% of the sample remained
      > or =10% below their maximum lifetime weight. However, small regains were
      common, and few persons were able to re-lose weight after any weight regain. Of
      the participants who gained any weight between baseline and year 1 (n = 1483;
      65.7%), only 11.0% returned to their baseline weight or below at year 2. Of the
      participants who relapsed, which was defined as a weight regain of > or =5% at
      year 1 (n = 575, or 25.5% of the sample), only 4.7% returned to their baseline
      weight or below at year 2, and only 12.9% re-lost at least half of their year 1
      gain by year 2. Logistic regression showed that recovery was related to gaining
      less at year 1 and to smaller increases in depressive symptoms between baseline
      and year 1. CONCLUSION: Although successful weight losers continued to maintain a
      large percentage of their weight losses over 2 y, recovery from even minor weight
      regain was uncommon.

PMID- 14668268
TI  - Dietary fiber and progression of atherosclerosis: the Los Angeles Atherosclerosis
      Study.
AB  - BACKGROUND: Several epidemiologic studies found weak protective relations between
      dietary fiber intake and the risk of cardiovascular disease events. However, few
      of the studies addressed possible mechanisms of the effect. OBJECTIVE: In the
      present study, we estimated relations between the progression of atherosclerosis
      and the intake of selective dietary fiber fractions. Mediation of the relations
      by serum lipids was also investigated. DESIGN: Participants who were free of
      heart disease and aged 40-60 y were recruited into the cohort (n = 573; 47%
      women). The intima-media thickness (IMT) of the common carotid arteries was
      measured ultrasonographically at the baseline examination and at 2 follow-up
      examinations (n = 500), dietary intakes were assessed with six 24-h recalls (3 at
      baseline and 3 at the first follow-up examination), and blood samples were
      analyzed at baseline and at both follow-up examinations. RESULTS: A significant
      inverse association was observed between IMT progression and the intakes of
      viscous fiber (P = 0.05) and pectin (P = 0.01). Correction for measurement error
      increased the magnitude of these estimated effects. The ratio of total to HDL
      cholesterol was inversely related to the intakes of total fiber (P = 0.01),
      viscous fiber (P = 0.05), and pectin (P = 0.01). The magnitude of the association
      between IMT progression and the intakes of viscous fiber and pectin was
      attenuated by adjustment for serum lipids. CONCLUSIONS: The intake of viscous
      fiber, especially pectin, appears to protect against IMT progression. Serum
      lipids may act as a mediator between dietary fiber intake and IMT progression.

PMID- 14668269
TI  - Hypertension is related to the degradation of dietary frying oils.
AB  - BACKGROUND: The family kitchen resembles an uncontrolled laboratory experiment,
      and some discrepancies in the relation between the risk of hypertension and
      dietary fat may be partly due to the manipulation to which the fats were
      subjected. OBJECTIVE: We investigated whether deterioration in the quality of the
      cooking oils in the family household contributes to the risk of high blood
      pressure. DESIGN: The study was cross-sectional. Anthropometric measurements were
      obtained for 1226 persons aged 18-65 y who were selected randomly from the
      municipal census of Pizarra, Spain. An oral-glucose-tolerance test was given to
      1020 of these persons. Samples of the cooking oil being used were taken from the
      kitchens of a random subset of 538 persons. The concentrations of polar compounds
      and polymers were used as markers of the deterioration of the oils. The strength
      of association between variables was measured by calculating the odds ratio from
      logistic models. RESULTS: Hypertension was strongly associated with obesity and
      was influenced by sex, diabetes, and age. The presence of excess polar compounds
      in the cooking oil and the use of sunflower oil were related to the risk of
      hypertension, whereas the concentration of monounsaturated fatty acids in the
      serum phospholipids was negatively related to this risk. These associations
      remained after inclusion in the models of age, sex, obesity, and the presence of
      carbohydrate metabolism disorder. CONCLUSIONS: The risk of hypertension is
      positively and independently associated with the intake of cooking oil polar
      compounds and inversely related to blood concentrations of monounsaturated fatty
      acids.

PMID- 14668271
TI  - Dietary patterns associated with risk factors for cardiovascular disease in
      healthy US adults.
AB  - BACKGROUND: Certain nutrients are well established as dietary risk factors for
      cardiovascular disease (CVD), but dietary patterns may be a better predictor of
      CVD risk. OBJECTIVE: This study tested the hypothesis that the complex dietary
      behaviors of US adults can be grouped into major dietary patterns that are
      related to risk factors for CVD. DESIGN: With the use of food-frequency
      questionnaire data from the third National Health and Nutrition Examination
      Survey, dietary patterns of healthy US adults (>/or =20 y old; n = 13 130) were
      identified by factor analysis. Log-transformed biomarker data were associated
      with major dietary patterns after control for confounding variables in regression
      analyses. All statistical analyses accounted for the survey design and sample
      weights. RESULTS: Of 6 dietary patterns identified, 2 patterns emerged as the
      most predominant: the Western pattern was characterized by high intakes of
      processed meats, eggs, red meats, and high-fat dairy products, and the American
      healthy pattern was characterized by high intakes of green, leafy vegetables;
      salad dressings; tomatoes; other vegetables (eg, peppers, green beans, corn, and
      peas); cruciferous vegetables; and tea. The Western pattern was associated (P <
      0.05) positively with serum C-peptide, serum insulin, and glycated hemoglobin and
      inversely with red blood cell folate concentrations after adjustment for
      confounding variables. The American-healthy pattern had no linear relation with
      any of the biomarkers examined. CONCLUSIONS: The identification of common dietary
      patterns among free-living persons is promising for characterizing high-risk
      groups at the US population level. The dietary patterns identified here are
      similar to those reported in other nonrepresentative samples and are associated
      with biomarkers of CVD risk, which confirms that dietary pattern analysis can be
      a valuable method for assessing dietary intakes when predicting CVD risk.

PMID- 14668270
TI  - Dietary linolenic acid is inversely associated with plasma triacylglycerol: the
      National Heart, Lung, and Blood Institute Family Heart Study.
AB  - BACKGROUND: Dietary intake of linolenic acid is associated with a decreased risk
      of cardiovascular disease mortality. However, the mechanisms by which dietary
      linolenic acid affects cardiovascular disease risk are not clearly understood.
      OBJECTIVE: We examined the association between dietary linolenic acid and plasma
      triacylglycerol concentrations. DESIGN: In a cross-sectional design, we studied
      4440 white subjects (2036 men and 2404 women) aged 25-93 y who participated in
      the National Heart, Lung, and Blood Institute Family Heart Study. We used
      generalized linear models to estimate adjusted mean triacylglycerol
      concentrations according to categories of total dietary linolenic acid (alpha-
      and gamma-linolenic acid) intake. RESULTS: The mean dietary linolenic acid
      intakes were 0.81 and 0.69 g/d for the men and the women, respectively. High
      consumption of dietary linolenic acid was associated with young age; high intakes
      of energy, fat, carbohydrates, fruit, vegetables, and fish; low HDL cholesterol;
      current smoking; and frequent consumption of creamy salad dressing. High
      consumption of dietary linolenic acid was also associated with low plasma
      triacylglycerol concentrations. From the lowest to the highest quintile of
      linolenic acid intake, the multivariate-adjusted mean triacylglycerol
      concentrations were 1.75 (95% CI: 1.65, 1.85), 1.74 (1.66, 1.82), 1.69 (1.61,
      1.77), 1.66 (1.58, 1.74), and 1.54 (1.44, 1.64) mmol/L, respectively (P for
      linear trend = 0.007). When linolenic acid was used as a continuous variable, the
      corresponding regression coefficient was -0.2811 (-0.4922, -0.07001).
      CONCLUSIONS: Consumption of total linolenic acid is inversely related to plasma
      triacylglycerol concentrations in both white men and white women. This suggests a
      pathway by which dietary linolenic acid might reduce cardiovascular disease risk.

PMID- 14668272
TI  - Bioelectrical impedance measurements in patients with gastrointestinal disease:
      validation of the spectrum approach and a comparison of different methods for
      screening for nutritional depletion.
AB  - BACKGROUND: Bioelectrical impedance spectroscopy (BIS) may be of value in
      identifying patients with nutritional depletion. OBJECTIVE: The primary aim of
      the study was to assess the validity of BIS in patients with gastrointestinal
      disease. The secondary aim was to compare different screening methods for
      identifying nutritionally depleted patients. DESIGN: In 70 patients with
      gastrointestinal disease, BIS measurements were performed and fluid compartments
      were calculated from extrapolated resistance (R) values of extracellular (R(ECW))
      and intracellular (R(ICW)) water based on mixture equations. Results were
      compared with total body water and ECW, which were measured by dilution methods.
      Patients were classified as depleted if their actual fat-free mass (FFM) was <90%
      of their ideal FFM (iFFM). Different screening approaches for depletion were
      compared: the impedance vector method and the resistance index (RI) in relation
      to iFFM (RI/iFFM). RESULTS: Total body water and ICW were largely underestimated
      (4 L) in the not-depleted patients but not in the depleted patients. In both
      groups, ECW was slightly overestimated (0.6-0.7 L). The critical frequency was
      60% higher and the membrane capacitance was 40% lower in the depleted than in the
      not-depleted patients. The impedance vector method failed to identify depleted
      patients, whereas the proposed ratio at R(50) (R measured at 50 kHz) and R(inf)
      (R at infinite frequency) resulted in comparable sensitivity (86%) and
      specificity (73-80%). CONCLUSIONS: BIS measures of body fluids are influenced by
      the presence of depletion, probably because of alterations in the electric
      properties of the body at the cellular level. However, for screening purposes,
      the use of the ratio (L(2)/R)/iFFM at R(50) and R(inf) may be of value.

PMID- 14668273
TI  - Diet and food insufficiency among Hispanic youths: acculturation and
      socioeconomic factors in the third National Health and Nutrition Examination
      Survey.
AB  - BACKGROUND: Low socioeconomic status is associated with poor diet, food
      insufficiency, and poor child health. Hispanic households have disproportionately
      low incomes. Acculturation-related changes may augment the effects of poverty on
      children's diet and health. OBJECTIVE: The goal was to determine the associations
      that acculturation, measured by parents' language use, and income have with
      dietary intakes and food insufficiency among Hispanic youths. DESIGN: Data on
      2985 Hispanic youths aged 4-16 y were from the third National Health and
      Nutrition Examination Survey (1988-1994). Nutrient intake data were from one 24-h
      dietary recall. The analysis was controlled for demographic, socioeconomic, and
      program variables. RESULTS: Parents' exclusive use of Spanish was associated in
      bivariate analyses with differences in intakes of energy, protein, sodium, and
      folate and in percentages of energy from fat and saturated fat. When other
      factors were controlled for, less acculturation was associated with differences
      in intakes of energy and sodium and in percentages of energy from fat and
      saturated fat. Individuals in poorer households had higher intakes of energy,
      protein, sodium, and some micronutrients. Although not significant for all
      indicators of food insufficiency, consistent patterns showed that household food
      insufficiency decreased with less acculturation (odds ratio: 0.4; 95% CI: 0.2,
      0.7 for adult meal size reduced) and increased with low income [odds ratio: 5.9
      (3.0, 11.7) for not enough food and 5.4 (2.2, 13.4) for child meal size reduced].
      CONCLUSIONS: Both acculturation and poverty have roles in children's diets and in
      household food insufficiency. Culturally specific public health and nutrition
      education should complement efforts to improve the financial security of low
      income households.

PMID- 14668274
TI  - Use of cod liver oil during the first year of life is associated with lower risk
      of childhood-onset type 1 diabetes: a large, population-based, case-control
      study.
AB  - BACKGROUND: In Norway, cod liver oil is an important source of dietary vitamin D
      and the long-chain n-3 fatty acids eicosapentaenoic acid and docosahexaenoic
      acid, all of which have biological properties of potential relevance for the
      prevention of type 1 diabetes. OBJECTIVE: The main objective was to investigate
      whether the use of dietary cod liver oil or other vitamin D supplements, either
      by the mother during pregnancy or by the child during the first year of life, is
      associated with a lower risk of type 1 diabetes among children. DESIGN: We
      designed a nationwide case-control study in Norway with 545 cases of childhood
      onset type 1 diabetes and 1668 population control subjects. Families were
      contacted by mail, and they completed a questionnaire on the frequency of use of
      cod liver oil and other vitamin D supplements and other relevant factors.
      RESULTS: Use of cod liver oil in the first year of life was associated with a
      significantly lower risk of type 1 diabetes (adjusted odds ratio: 0.74; 95% CI:
      0.56, 0.99). Use of other vitamin D supplements during the first year of life and
      maternal use of cod liver oil or other vitamin D supplements during pregnancy
      were not associated with type 1 diabetes. CONCLUSION: Cod liver oil may reduce
      the risk of type 1 diabetes, perhaps through the antiinflammatory effects of long
      chain n-3 fatty acids.

PMID- 14668275
TI  - Meal modulation of circulating interleukin 18 and adiponectin concentrations in
      healthy subjects and in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: A single high-fat meal induces endothelial activation, which is
      associated with increased serum concentrations of inflammatory cytokines.
      OBJECTIVE: We compared the effect of 3 different meals on circulating
      concentrations of interleukin 8 (IL-8), interleukin 18 (IL-18), and adiponectin
      in healthy subjects and in patients with type 2 diabetes mellitus. DESIGN: Thirty
      patients with newly diagnosed type 2 diabetes and 30 matched, nondiabetic
      subjects received the following 3 isoenergetic (780 kcal) meals separated by 1-wk
      intervals: a high-fat meal; a high-carbohydrate, low-fiber (4.5 g) meal; and a
      high-carbohydrate, high-fiber meal in which refined-wheat flour was replaced with
      whole-wheat flour (16.8 g). We analyzed serum glucose and lipid variables and
      serum IL-8, IL-18, and adiponectin concentrations at baseline and at 2 and 4 h
      after ingestion of the meals. RESULTS: Compared with nondiabetic subjects,
      diabetic patients had higher fasting IL-8 (P < 0.05) and IL-18 (P < 0.01)
      concentrations and lower adiponectin concentrations (P < 0.01) at baseline. In
      both nondiabetic and diabetic subjects, IL-18 concentrations increased and
      adiponectin concentrations decreased (P < 0.05) from baseline concentrations
      after consumption of the high-fat meal. After consumption of the high
      carbohydrate, high-fiber meal, serum IL-18 concentrations decreased from baseline
      concentrations (P < 0.05) in both nondiabetic and diabetic subjects; adiponectin
      concentrations decreased after the high-carbohydrate, low-fiber meal in diabetic
      patients. IL-8 concentrations did not change significantly after consumption of
      any of the 3 meals. CONCLUSIONS: This study provides evidence that circulating IL
      18 and adiponectin concentrations are modulated by familiar foodstuffs in humans.
      Meal modulation of cytokines involved in atherogenesis may represent a safe
      strategy for ameliorating atherogenetic inflammatory activity in diabetic
      patients.

PMID- 14668276
TI  - Variability of measured resting metabolic rate.
AB  - BACKGROUND: The necessity of a 12-h fast before resting metabolic rate (RMR) is
      measured is often a barrier to measuring RMR. OBJECTIVE: We compared RMR
      measurements obtained in the morning and afternoon and across repeated days to
      elucidate the magnitude and sources of variability. DESIGN: Healthy men (n = 12)
      and women (n = 25) aged 21-67 y, with body mass indexes (in kg/m(2)) ranging from
      17 to 34 and body fat ranging from 6% to 54%, completed 4 RMR measurements. RMR
      measurements were made in the morning (after a 12-h fast and 12 h postexercise)
      and in the afternoon (after a 4-h fast and 12 h postexercise) on 2 separate days
      with the ventilated-hood technique. Body composition was assessed by dual-energy
      X-ray absorptiometry. RESULTS: Mean (+/- SE) afternoon RMR was significantly
      higher than morning RMR on both visit 1 (1593.5 +/- 35.6 compared with 1508.0 +/-
      31.5 kcal/d; P = 0.001) and visit 2 (1602 +/- 29.3 compared with 1511.4 +/- 35.9
      kcal/d; P = 0.001). The 2 morning measurements (r = 0.93) and the 2 afternoon
      measurements (r = 0.93) were highly correlated, and no significant differences
      between measurements were observed. The mean difference between the morning and
      afternoon measurements was 99.0 +/- 35.8 kcal/d (6%). CONCLUSIONS: Repeated
      morning and evening measurements of RMR were stable and highly correlated. Day-to
      day measurements of RMR were not significantly different. RMR measured in the
      afternoon after a 4-h fast and exercise was approximately 100 kcal/d higher than
      RMR measured in the morning.

PMID- 14668277
TI  - Intestinal parasites increase the dietary lysine requirement in chronically
      undernourished Indian men.
AB  - BACKGROUND: We previously used the 24-h indicator amino acid balance method to
      show that the lysine requirement in undernourished Indian men from low
      socioeconomic and unsanitary environments is approximately 50% higher than the
      mean requirement of 30 mg lysine. kg(-1). d(-1) in well-nourished men. OBJECTIVE:
      It is possible that this higher lysine requirement in persons with chronic
      undernutrition is due to environmental influences, including the presence of
      intestinal parasites. We assessed this possibility by using 24-h indicator amino
      acid balance (with leucine) at both the "normal" requirement for lysine intake
      and the higher requirement, before and after successful treatment to eradicate
      intestinal parasites in affected, undernourished men. DESIGN: Fourteen
      chronically undernourished men were studied before and after treatment for
      intestinal parasites, during each of two 7-d (6-d dietary adaptation plus 1-d
      tracer experiment) diet periods supplying either 30 (n = 7) or 45 (n = 7) mg
      lysine. kg(-1). d(-1) from an L-amino acid diet. Twenty-four-hour indicator amino
      acid balance was estimated on day 6 by [(13)C]leucine tracer infusion. RESULTS:
      Before the parasite treatment, subjects were in neutral 24-h leucine balance at
      both lysine intakes. After the eradication of intestinal parasites, there was a
      significant (P < 0.001) improvement in 24-h leucine balances, which were positive
      at both lysine intakes. CONCLUSIONS: On the basis of the 24-h indicator amino
      acid balance approach, it appears that intestinal infestation with parasites
      increases the requirement for lysine and that this may be one factor responsible
      for the higher lysine requirement observed in persons with chronic
      undernutrition.

PMID- 14668278
TI  - Water-miscible, emulsified, and solid forms of retinol supplements are more toxic
      than oil-based preparations.
AB  - BACKGROUND: It is well established that an excessive intake of retinol (vitamin
      A) is toxic; however, it has been > 25 y since the last extensive treatise of
      case reports on this subject. OBJECTIVE: The objectives were to identify and
      evaluate all individual cases of retinol toxicity published in the scientific
      literature that assessed the thresholds and symptoms induced by high intakes of
      retinol and to compare the toxicity of different physical forms of retinol
      preparations. DESIGN: We performed a meta-analysis of case reports on toxicity
      claimed to be induced by intakes of excessive amounts of dietary retinol (ie,
      retinol and retinyl esters in foods or supplements). Using free text and MESH
      (medical subheading) strategies in PubMed, we identified 248 articles in the
      scientific literature. From these initial articles we identified other relevant
      citations. The final database consisted of 259 cases in which individual data on
      dose, sex, age, time of exposure, and symptoms are reported. RESULTS: Chronic
      hypervitaminosis A is induced after daily doses of 2 mg retinol/kg in oil-based
      preparations for many months or years. In contrast, doses as low as 0.2 mg
      retinol. kg(-1). d(-1) in water-miscible, emulsified, and solid preparations for
      only a few weeks caused chronic hypervitaminosis A. Thus, water-miscible,
      emulsified, and solid preparations of retinol are approximately 10 times as toxic
      as are oil-based retinol preparations. The safe upper single dose of retinol in
      oil or liver seems to be approximately 4-6 mg/kg body wt. These thresholds do not
      vary considerably with age. CONCLUSIONS: The results of the present study
      indicate that the physical form of retinol supplements is a major determinant of
      toxicity. The use of water-miscible, emulsified, and solid preparations of
      retinol should therefore be carefully considered before being used in supplements
      and fortifications.

PMID- 14668279
TI  - Body iron stores and their determinants in healthy postmenopausal US women.
AB  - BACKGROUND: Data on the determinants of body iron stores in middle-aged women are
      sparse. OBJECTIVE: We prospectively evaluated nondietary and dietary determinants
      of iron stores. DESIGN: Using blood samples collected in 1989-1990, we measured
      plasma ferritin concentrations in 620 healthy postmenopausal women aged 44-69 y
      who participated in the Nurses' Health Study. Food-frequency questionnaires
      completed in 1980, 1984, and 1986 were used to calculate average dietary intakes.
      Generalized linear regression and multiple logistic regression models were used
      to assess the association between plasma ferritin and its determinants. RESULTS:
      Among these postmenopausal women, the median plasma ferritin concentration was
      73.8 ng/mL (interquartile range: 41.6-125.8 ng/mL), 2.7% were iron depleted
      (ferritin concentration < 12 ng/mL), and 9.8% had an elevated ferritin
      concentration (> 200 ng/mL). Age, time since menopause, time since the last
      postmenopausal hormone (PMH) use, body mass index, iron supplement use, and
      alcohol and heme-iron intakes were positively associated with ferritin
      concentrations, whereas PMH use, physical activity, aspirin use, and
      gastrointestinal ulcer were inversely related. The association between heme-iron
      intake and ferritin was most apparent among the women who consumed > 30 g
      alcohol/d. CONCLUSIONS: Our prospective data confirm that in postmenopausal
      women, intakes of heme iron, supplemental iron, and alcohol are dietary
      determinants of plasma ferritin, and age, PMH use, body mass index, physical
      activity, aspirin use, and gastrointestinal ulcer are nondietary determinants.

PMID- 14668280
TI  - High-, but not low-bioavailability diets enable substantial control of women's
      iron absorption in relation to body iron stores, with minimal adaptation within
      several weeks.
AB  - BACKGROUND: Adaptation of iron absorption in response to dietary iron
      bioavailability is less likely in premenopausal women, who generally have lower
      iron stores, than in men. OBJECTIVE: The objective of the study was to ascertain
      whether iron absorption in women adapts to dietary iron bioavailability and
      whether adaptation reflects altered absorptive efficiency or adjustment to
      specific inhibitors or enhancers of absorption. DESIGN: Heme- and nonheme-iron
      absorption from either high- or low-bioavailability diets was measured at 0 and
      10 wk in premenopausal women as they consumed one of the diets for 12 wk
      (randomized 2 x 2 factorial design). The high- and low-bioavailability diets
      contained similar amounts of total iron, as 13.1 and 14.8 mg/d nonheme and 2.0
      and 0.3 mg/d heme iron, respectively, and they differed in contents of meat,
      ascorbate, whole grains, legumes, and tea. RESULTS: In premenopausal women, the
      efficiency of nonheme-iron absorption (P = 0.06, two-tailed test), but not of
      heme-iron absorption, tended to adapt in response to a 12-wk difference in
      dietary iron bioavailability, whether absorption was tested with high- or low
      bioavailability menus. Bioavailability, but not adaptation, substantially
      influenced total iron absorption (approximately 6-fold). In contrast with iron
      absorption from the low-bioavailability diet, that from the high-bioavailability
      diet consistently was inversely associated with serum ferritin. CONCLUSION: Only
      the high-bioavailability diet enabled women to absorb more iron in relation to
      their low iron stores. Women consuming the high-bioavailability diet absorbed up
      to 4.5 mg (30-35%) dietary iron with minimal influence of the diet consumed
      during the previous 10 wk.

PMID- 14668281
TI  - Role of the small intestine in postpartum weight retention in mice.
AB  - BACKGROUND: Approximately 25% of women retain 5 kg of the weight gained during
      pregnancy, but the physiologic factors underlying excessive postpartum weight
      gain are not known. OBJECTIVE: The objective of the study was to determine
      whether pregnancy-related adaptive increases in intestinal nutrient transport are
      retained after parturition and therefore contribute to postpartum weight gain.
      DESIGN: We measured body weight and intestinal nutrient transport in virgin (V,
      control), primiparous (P, one pregnancy), and multiparous (M, 3 pregnancies) mice
      at parturition (day 1), during lactation (days 14 and 21), at weaning (day 28),
      after weaning (day 40), and during aging (days 70, 120, 200, and 300). RESULTS:
      In M and P mice, body weight and the weight and length of the small intestine
      were greatest during lactation; they then decreased but did not return to
      prepregnancy values until 300 d after parturition. Intestinal villus heights were
      maximal at lactation and remained high < or = 200 d after parturition. Total
      intestinal transport capacity for D-glucose, D-fructose, and L-proline was also
      greatest during lactation, and the lactation-enhanced transport capacity was
      retained < or = 70 d after parturition. M mice retained more body weight and
      intestinal transport capacity postpartum than did P mice. Aging per se had little
      or no effect on body weight or intestinal weight, length, and nutrient transport.
      The dramatic, lactation-related increases in intestinal nutrient transport
      capacity were due mainly to increases in intestinal mass. CONCLUSIONS: Postpartum
      retention of pregnancy- and lactation-related increases in intestinal nutrient
      uptake capacity may play a significant role in postpartum body weight retention.
      These adaptive increases may be cumulative and may result in greater weight
      retention in mice with multiple pregnancies.

PMID- 14668282
TI  - Calcium absorption is significantly higher in adolescents during pregnancy than
      in the early postpartum period.
AB  - BACKGROUND: Early childbearing may limit skeletal consolidation and increase
      calcium demands in adolescents. OBJECTIVE: The purpose of this study was to
      characterize calcium absorption in pregnant and lactating adolescents. DESIGN:
      Fractional calcium absorption was evaluated in 23 adolescents (mean +/- SD age:
      16.5 +/- 1.4 y) during the third trimester of pregnancy (34.7 +/- 1.0 wk
      gestation) and again in 15 of these adolescents 31 +/- 8 d after delivery. Eight
      adolescents were breastfeeding their infants during the follow-up study.
      Fractional calcium absorption was determined by using oral ((46)Ca or (44)Ca) and
      intravenous ((42)Ca) stable calcium isotopes. Total-body and lumbar spine bone
      mineral density were measured in adolescents during the postpartum period by
      using dual-energy X-ray absorptiometry. RESULTS: Fractional calcium absorption
      was significantly greater during pregnancy than at 3-4 wk postpartum [0.526 +/-
      0.152 (n = 23) compared with 0.297 +/- 0.108 (n = 15); P < 0.0001]. Lumbar spine
      z scores measured 19-44 d after delivery (n = 15) were significantly associated
      with calcium intake during pregnancy (y = -3.53 + 0.107x; R(2) = 0.355, P < 0.02)
      and were inversely related to fractional calcium absorption during pregnancy (y =
      3.489 - 6.66x; R(2) = 0.52, P = 0.002). A total of 33% (5/15) of adolescents had
      lumbar spine z scores that met the definition of osteopenia (n = 3) or
      osteoporosis (n = 2) in the early postpartum period. CONCLUSIONS: Calcium
      absorption in adolescents was significantly higher during the third trimester of
      pregnancy than in the early postpartum period, and higher calcium intakes during
      pregnancy appeared to be protective against loss of trabecular bone at the lumbar
      spine.

PMID- 14668283
TI  - Effects of maternal micronutrient supplementation on fetal loss and infant
      mortality: a cluster-randomized trial in Nepal.
AB  - BACKGROUND: We previously reported that maternal micronutrient supplementation in
      rural Nepal decreased low birth weight by approximately 15%. OBJECTIVE: We
      examined the effect of daily maternal micronutrient supplementation on fetal loss
      and infant mortality. DESIGN: The study was a double-blind, cluster-randomized,
      controlled trial among 4926 pregnant women and their 4130 infants in rural Nepal.
      In addition to vitamin A (1000 microg retinol equivalents), the intervention
      groups received either folic acid (FA; 400 microg), FA + iron (60 mg), FA + iron
      + zinc (30 mg), or multiple micronutrients (MNs; the foregoing plus 10 microg
      vitamin D, 10 mg vitamin E, 1.6 mg thiamine, 1.8 mg riboflavin, 2.2 mg vitamin B
      6, 2.6 microg vitamin B-12, 100 mg vitamin C, 64 microg vitamin K, 20 mg niacin,
      2 mg Cu, and 100 mg Mg). The control group received vitamin A only. RESULTS: None
      of the supplements reduced fetal loss. Compared with control infants, infants
      whose mothers received FA alone or with iron or iron + zinc had a consistent
      pattern of 15-20% lower 3-mo mortality; this pattern was not observed with MNs.
      The effect on mortality was restricted to preterm infants, among whom the
      relative risks (RRs) were 0.36 (95% CI: 0.18, 0.75) for FA, 0.53 (0.30, 0.92) for
      FA + iron, 0.77 (0.45, 1.32) for FA + iron + zinc, and 0.70 (0.41, 1.17) for MNs.
      Among term infants, the RR for mortality was close to 1 for all supplements
      except MNs (RR: 1.74; 95% CI: 1.00, 3.04). CONCLUSIONS: Maternal micronutrient
      supplementation failed to reduce overall fetal loss or early infant mortality.
      Among preterm infants, FA alone or with iron reduced mortality in the first 3 mo
      of life. MNs may increase mortality risk among term infants, but this effect
      needs further evaluation.

PMID- 14668284
TI  - Iron supplementation during infancy--effects on expression of iron transporters,
      iron absorption, and iron utilization in rat pups.
AB  - BACKGROUND: Studies conducted in human infants suggest developmental changes in
      the regulation of iron absorption; however, little is known about the molecular
      mechanisms regulating iron absorption during infancy. Two intestinal iron
      transporters, divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1), were
      recently identified. OBJECTIVE: The objective was to investigate at a molecular
      level the regulation of iron absorption during infancy in a rat pup model. We
      examined the developmental expression of DMT1 and FPN1 and the effects of iron
      supplementation on their expression and on iron absorption and utilization during
      infancy. DESIGN: Rat pups were given daily oral doses of 0, 30, or 150 microg Fe
      from day 2 to day 20 after birth. On days 10 and 20 after birth, (59)Fe
      absorption, tissue minerals, and intestinal DMT1, FPN1, and ferritin expression
      were examined. To assess developmental expression, DMT1 and FPN1 were examined in
      control rats from days 1 to 50 after birth. RESULTS: Intestinal DMT1 and FPN1
      were significantly affected by age; expression increased dramatically by day 40.
      On day 10, no significant effect of iron supplementation on DMT1 and FPN1 gene
      expression or on iron absorption was observed. By day 20, DMT1 and FPN1
      expression and iron absorption had decreased significantly with iron
      supplementation. CONCLUSIONS: During early infancy, rat pups are unable to down
      regulate intestinal iron transporters or iron absorption in response to iron
      supplementation, whereas down-regulation occurs during late infancy. The current
      findings provide evidence of the developmental regulation of iron absorption,
      which emphasizes the need for caution when giving iron supplements to infants at
      an early age.

PMID- 14668285
TI  - Predictors of body fat gain in nonobese girls with a familial predisposition to
      obesity.
AB  - BACKGROUND: Conflicting evidence exists on the causal factors underlying the
      development of excess adiposity in children. OBJECTIVE: We determined the effect
      of energy expenditure (EE), muscle energetics, and physical fitness on weight and
      fat gain in prepubertal girls with or without a predisposition to obesity.
      DESIGN: Normal-weight girls (n = 101) were recruited at 8 y of age according to
      parental body mass index. Eighty-eight girls completed the 2-y study, and the
      groups were as follows: LN, girls with 2 lean parents; LNOB, girls with 1 obese
      and 1 lean parent; and OB, girls with 2 obese parents. Measurements of weight,
      height, and body composition were taken 1 and 2 y after baseline. Girls underwent
      baseline measurements of EE by 24-h calorimetry and doubly labeled water, of
      muscle metabolism by (31)P nuclear magnetic resonance, and of fitness. RESULTS:
      Fat mass (FM) and percentage body fat (%BF) differed significantly between the
      groups at years 1 and 2; the OB group had higher FM (P = 0.03) and %BF (P =
      0.046) at year 1 and higher FM (P = 0.047) at year 2 than did the LN group. After
      adjustment for baseline weight, group, time, ethnicity, and Tanner stage, sleep
      EE, basal EE, 24-h EE, and peak oxygen uptake were negatively associated with FM
      and %BF (P < 0.04). After adjustment for the same variables, muscle oxidative
      capacity and free-living total EE were negatively and positively predictive,
      respectively, of changes in %BF between 8 and 10 y of age (both P = 0.04).
      CONCLUSIONS: Nonobese girls with 2 obese parents have a significant risk of
      developing obesity. High free-living total EE and low muscle oxidative capacity
      predict high rates of fat gain.

PMID- 14668286
TI  - Lycopene, beta-carotene, and colorectal adenomas.
AB  - BACKGROUND: Epidemiologic studies found that high tomato intakes reduce the risk
      of colorectal cancers. This beneficial effect is assumed to be caused by high
      intakes of lycopene, a carotenoid with strong antioxidant activity that is
      present predominantly in tomatoes. OBJECTIVE: We assessed the relation between
      plasma lycopene concentrations and colorectal adenomas, the precursors for most
      colorectal cancers. In addition, the concentrations of 2 other antioxidants, beta
      carotene and alpha-tocopherol, were measured. DESIGN: White subjects undergoing a
      complete colonoscopy were included in the study (73 with adenomas, 63 without any
      polyps, and 29 with hyperplastic polyps). A detailed dietary history and
      information on alcohol consumption and smoking habits were collected from all
      subjects. Plasma lycopene, beta-carotene, and alpha-tocopherol concentrations
      were measured by using HPLC. RESULTS: Patients with adenomas and control subjects
      without polyps did not differ significantly in body mass index; intakes of
      energy, fat, protein, carbohydrates, fiber, beta-carotene, and alcohol; or
      prevalence of smoking, but patients with adenomas were slightly older. The median
      plasma lycopene concentration was significantly lower in the adenoma group than
      in the control group (-35%; P = 0.016). The median plasma beta-carotene
      concentration also tended to be lower in the adenoma group (-25.5%), but the
      difference was not significant. In the multiple logistic regression, only smoking
      (odds ratio: 3.02; 95% CI: 1.46, 6.25; P = 0.003) and a plasma lycopene
      concentration < 70 microg/L (odds ratio: 2.31; 1.12, 4.77; P = 0.023) were risk
      factors for adenomatous polyps. Patients with hyperplastic polyps did not differ
      significantly from control subjects in any variable. CONCLUSION: Our findings
      support the hypothesis that lycopene contributes to the protective effect of high
      tomato intakes against the risk of colorectal adenomas.

PMID- 14668287
TI  - High serum ferritin is not identical to high iron stores.

PMID- 14668289
TI  - Conflicting evidence of iron and zinc interactions in humans: does iron affect
      zinc absorption?

PMID- 14668290
TI  - A neural network model of flexible spatial updating.
AB  - Neurons in many cortical areas involved in visuospatial processing represent
      remembered spatial information in retinotopic coordinates. During a gaze shift,
      the retinotopic representation of a target location that is fixed in the world
      (world-fixed reference frame) must be updated, whereas the representation of a
      target fixed relative to the center of gaze (gaze-fixed) must remain constant. To
      investigate how such computations might be performed, we trained a 3-layer
      recurrent neural network to store and update a spatial location based on a gaze
      perturbation signal, and to do so flexibly based on a contextual cue. The network
      produced an accurate readout of target position when cued to either reference
      frame, but was less precise when updating was performed. This output mimics the
      pattern of behavior seen in animals performing a similar task. We tested whether
      updating would preferentially use gaze position or gaze velocity signals, and
      found that the network strongly preferred velocity for updating world-fixed
      targets. Furthermore, we found that gaze position gain fields were not present
      when velocity signals were available for updating. These results have
      implications for how updating is performed in the brain.

PMID- 14668291
TI  - Differential contribution of early visual areas to the perceptual process of
      contour processing.
AB  - We investigated contour processing and figure-ground detection within human
      retinotopic areas using event-related functional magnetic resonance imaging
      (fMRI) in 6 healthy and naive subjects. A figure (6 degrees side length) was
      created by a 2nd-order texture contour. An independent and demanding foveal
      letter-discrimination task prevented subjects from noticing this more peripheral
      contour stimulus. The contour subdivided our stimulus into a figure and a ground.
      Using localizers and retinotopic mapping stimuli we were able to subdivide each
      early visual area into 3 eccentricity regions corresponding to 1) the central
      figure, 2) the area along the contour, and 3) the background. In these subregions
      we investigated the hemodynamic responses to our stimuli and compared responses
      with or without the contour defining the figure. No contour-related blood
      oxygenation level-dependent modulation in early visual areas V1, V3, VP, and MT+
      was found. Significant signal modulation in the contour subregions of V2v, V2d,
      V3a, and LO occurred. This activation pattern was different from comparable
      studies, which might be attributable to the letter-discrimination task reducing
      confounding attentional modulation. In V3a, but not in any other retinotopic
      area, signal modulation corresponding to the central figure could be detected.
      Such contextual modulation will be discussed in light of the recurrent processing
      hypothesis and the role of visual awareness.

PMID- 14668292
TI  - Temporal dynamics of binocular disparity processing in the central visual
      pathway.
AB  - To solve the stereo correspondence problem (i.e., find the matching features of a
      visual scene in both eyes), it is advantageous to combine information across
      spatial scales. The details of how this is accomplished are not clear.
      Psychophysical studies and mathematical models have suggested various types of
      interactions across spatial scale, including coarse to fine, fine to coarse,
      averaging, and population coding. In this study, we investigate dynamic changes
      in disparity tuning of simple and complex cells in the cat's striate cortex over
      a short time span. We find that disparity frequency increases and disparity
      ranges decrease while optimal disparity remains constant, and this conforms to a
      coarse-to-fine mechanism. We explore the origin of this mechanism by examining
      the frequency and size dynamics exhibited by binocular simple cells and neurons
      in the lateral geniculate nucleus (LGN). The results suggest a strong role for a
      feed-forward mechanism, which could originate in the retina. However, we find
      that the dynamic changes seen in the disparity range of simple cells cannot be
      predicted from their left and right eye monocular receptive field (RF) size
      changes. This discrepancy suggests the possibility of a dynamic nonlinearity or
      disparity specific feedback that alters tuning or a combination of both
      mechanisms.

PMID- 14668293
TI  - Functional connectivity of disparity-tuned neurons in the visual cortex.
AB  - Different mechanisms have been proposed concerning how disparity-tuned neurons
      might be connected to produce the signals for depth perception. Here we present
      neurophysiological evidence providing insight on this issue. We have recorded
      simultaneously from pairs of disparity-tuned neurons in the cat's striate cortex.
      The purpose was to determine the relationships between disparity tuning and
      functional connectivity revealed through neural cross-correlograms. Monosynaptic
      connections tend to be stronger between pairs of cells with similar disparity
      tuning. Pairs of complex cells tend to have either similar tuning or nearly
      opposite tuning with an absence of quadrature relations. Pairs with at least one
      simple cell do have some nearly quadrature relationships when they are recorded
      from the same electrode. Coarse-to-fine connections (i.e., the presynaptic cell
      has lower disparity frequency and larger disparity range) tend to be stronger but
      less frequent than those of a fine-to-coarse nature. Our results are consistent
      with a system that produces weighted averaging across cells that are tuned to
      similar disparities but different disparity scales to reduce false matches.

PMID- 14668294
TI  - Interpretation of a discontinuity in the sense of verticality at large body tilt.
AB  - Results of earlier spatial-orientation studies focusing on the sense of
      verticality have emphasized an intriguing paradox. Despite evidence that nearly
      veridical signals for gravicentric head orientation and egocentric visual
      stimulus orientation are available, roll-tilted subjects err in the direction of
      the long body axis when adjusting a visual line to vertical in darkness (Aubert
      effect). This has led to the suggestion that a central egocentric bias signal
      with fixed strength and direction acts to pull the perceived vertical to the
      subjects' zenith (M-model). In the present study, the subjective visual vertical
      (SVV) was tested in six human subjects, across the entire 360 degrees range. For
      comparison, body-tilt estimates from four subjects where collected in a separate
      series of experiments. For absolute tilts up to approximately 135 degrees, SVV
      responses showed a gradually increasing Aubert effect that could not be
      attributed to errors in perceived body tilt but was nicely in line with the M
      model. At larger absolute tilts, SVV errors abruptly reversed sign, now showing a
      pattern concordant with errors in body-tilt estimates but incompatible with the M
      model. These results suggest that, in the normal working range, the perception of
      external space and the perception of body posture are based on different
      processing of body-tilt signals. Beyond this range, both spatial-orientation
      tasks seem to rely mainly on a common tilt signal.

PMID- 14668295
TI  - Reduced muscle selectivity during individuated finger movements in humans after
      damage to the motor cortex or corticospinal tract.
AB  - We investigated how damage to the motor cortex or corticospinal tract affects the
      selective activation of finger muscles in humans. We hypothesized that damage
      relatively restricted to the motor cortex or corticospinal tract would result in
      unselective muscle activations during an individuated finger movement task.
      People with pure motor hemiparesis attributed to ischemic cerebrovascular
      accident were tested. Pure motor hemiparetic and control subjects were studied
      making flexion/extension and then abduction/adduction finger movements. During
      the abduction/adduction movements, we recorded muscle activity from 3 intrinsic
      finger muscles: the abductor pollicis brevis, the first dorsal interosseus, and
      the abductor digit quinti. Each of these muscles acts as an agonist for only one
      of the abduction/adduction movements and might therefore be expected to be active
      in a highly selective manner. Motor cortex or corticospinal tract damage in
      people with pure motor hemiparesis reduced the selectivity of finger muscle
      activation during individuated abduction/adduction finger movements, resulting in
      reduced independence of these movements. Abduction/adduction movements showed a
      nonsignificant trend toward being less independent than flexion/extension
      movements in the affected hands of hemiparetic subjects. These changes in the
      selectivity of muscle activation and the consequent decrease in individuation of
      movement were correlated with decreased hand function. Our findings imply that,
      in humans, spared cerebral motor areas and descending pathways that remain might
      activate finger muscles, but cannot fully compensate for the highly selective
      control provided by the primary motor cortex and the crossed corticospinal
      system.

PMID- 14668296
TI  - Tuning of a basic coordination pattern constructs straight-ahead and curved
      walking in humans.
AB  - We tested the hypothesis that common principles govern the production of the
      locomotor patterns for both straight-ahead and curved walking. Whole body
      movement recordings showed that continuous curved walking implies substantial,
      limb-specific changes in numerous gait descriptors. Principal component analysis
      (PCA) was used to uncover the spatiotemporal structure of coordination among
      lower limb segments. PCA revealed that the same kinematic law accounted for the
      coordination among lower limb segments during both straight-ahead and curved
      walking, in both the frontal and sagittal planes: turn-related changes in the
      complex behavior of the inner and outer limbs were captured in limb-specific
      adaptive tuning of coordination patterns. PCA was also performed on a data set
      including all elevation angles of limb segments and trunk, thus encompassing 13
      degrees of freedom. The results showed that both straight-ahead and curved
      walking were low dimensional, given that 3 principal components accounted for
      more than 90% of data variance. Furthermore, the time course of the principal
      components was unchanged by curved walking, thereby indicating invariant
      coordination patterns among all body segments during straight-ahead and curved
      walking. Nevertheless, limb- and turn-dependent tuning of the coordination
      patterns encoded the adaptations of the limb kinematics to the actual direction
      of the walking body. Absence of vision had no significant effect on the
      intersegmental coordination during either straight-ahead or curved walking. Our
      findings indicate that kinematic laws, probably emerging from the interaction of
      spinal neural networks and mechanical oscillators, subserve the production of
      both straight-ahead and curved walking. During locomotion, the descending command
      tunes basic spinal networks so as to produce the changes in amplitude and phase
      relationships of the spinal output, sufficient to achieve the body turn.

PMID- 14668297
TI  - Processing deficits in primary visual cortex of amblyopic cats.
AB  - Early esotropic squint frequently results in permanent visual deficits in one
      eye, referred to as strabismic amblyopia. The neurophysiological substrate
      corresponding to these deficits is still a matter of investigation.
      Electrophysiological evidence is available for disturbed neuronal interactions in
      both V1 and higher cortical areas. In this study, we investigated the modulation
      of responses in cat V1 to gratings at different orientations and spatial
      frequencies (SFs; 0.1-2.0 cycles/degrees) with optical imaging of intrinsic
      signals. Maps evoked by both eyes were well modulated at most spatial
      frequencies. The layout of the maps resembled that of normal cats, and iso
      orientation domains tended to cross adjacent ocular dominance borders
      preferentially at right angles. Visually evoked potentials (VEPs) were recorded
      at SFs ranging from 0.1 to 3.5 cycles/degrees and revealed a consistently weaker
      eye for the majority of squinting cats. At each SF, interocular differences in
      VEP amplitudes corresponded well with differences in orientation response and
      selectivity in the maps. At 0.7-1.3 cycles/ degrees, population orientation
      selectivity was significantly lower for the weaker eye in cats with VEP
      differences compared with those with no VEP amplitude differences. In addition,
      the cutoff SF, above which gratings no longer induced orientation maps, was lower
      for the weaker eye (> or =1.0 cycles/degrees). These data reveal a close
      correlation between the loss of visual acuity in amblyopia as assessed by VEPs
      and the modulation of neuronal activation as seen by optical imaging of intrinsic
      signals. Furthermore, the results indicate that amblyopia is associated with
      altered intracortical processing already in V1.

PMID- 14668298
TI  - Sleep deprivation effects on growth factor expression in neonatal rats: a
      potential role for BDNF in the mediation of delta power.
AB  - The sleeping brain differs from the waking brain in its electrophysiological and
      molecular properties, including the expression of growth factors and immediate
      early genes (IEG). Sleep architecture and homeostatic regulation of sleep in
      neonates is distinct from that of adults. Hence, the present study addressed the
      question whether the unique homeostatic response to sleep deprivation in neonates
      is reflected in mRNA expression of the IEG cFos, brain-derived nerve growth
      factor (BDNF), and basic fibroblast growth factor (FGF2) in the cortex. As sleep
      deprivation is stressful to developing rats, we also investigated whether the
      increased levels of corticosterone would affect the expression of growth factors
      in the hippocampus, known to be sensitive to glucocorticoid levels. At postnatal
      days 16, 20, and 24, rats were subjected to sleep deprivation, maternal
      separation without sleep deprivation, sleep deprivation with 2 h recovery sleep,
      or no intervention. mRNA expression was quantified in the cortex and hippocampus.
      cFos was increased after sleep deprivation and was similar to control level after
      2 h recovery sleep irrespective of age or brain region. BDNF was increased by
      sleep deprivation in the cortex at P20 and P24 and only at P24 in the
      hippocampus. FGF2 increased during recovery sleep at all ages in both brain
      regions. We conclude that cortical BDNF expression reflects the onset of adult
      sleep-homeostatic response, whereas the profile of expression of both growth
      factors suggests a trophic effect of mild sleep deprivation.

PMID- 14668299
TI  - Cellular effects of deep brain stimulation: model-based analysis of activation
      and inhibition.
AB  - Deep brain stimulation (DBS) is an effective therapy for medically refractory
      movement disorders. However, fundamental questions remain about the effects of
      DBS on neurons surrounding the electrode. Experimental studies have produced
      apparently contradictory results showing suppression of activity in the
      stimulated nucleus, but increased inputs to projection nuclei. We hypothesized
      that cell body firing does not accurately reflect the efferent output of neurons
      stimulated with high-frequency extracellular pulses, and that this decoupling of
      somatic and axonal activity explains the paradoxical experimental results. We
      studied stimulation using the combination of a finite-element model of the
      clinical DBS electrode and a multicompartment cable model of a thalamocortical
      (TC) relay neuron. Both the electric potentials generated by the electrode and a
      distribution of excitatory and inhibitory trans-synaptic inputs induced by
      stimulation of presynaptic terminals were applied to the TC relay neuron. The
      response of the neuron to DBS was primarily dependent on the position and
      orientation of the axon with respect to the electrode and the stimulation
      parameters. Stimulation subthreshold for direct activation of TC relay neurons
      caused suppression of intrinsic firing (tonic or burst) activity during the
      stimulus train mediated by activation of presynaptic terminals. Suprathreshold
      stimulation caused suppression of intrinsic firing in the soma, but generated
      efferent output at the stimulus frequency in the axon. This independence of
      firing in the cell body and axon resolves the apparently contradictory
      experimental results on the effects of DBS. In turn, the results of this study
      support the hypothesis of stimulation-induced modulation of pathological network
      activity as a therapeutic mechanism of DBS.

PMID- 14668300
TI  - In vivo multiphoton microscopy of deep brain tissue.
AB  - Although fluorescence microscopy has proven to be one of the most powerful tools
      in biology, its application to the intact animal has been limited to imaging
      several hundred micrometers below the surface. The rest of the animal has eluded
      investigation at the microscopic level without excising tissue or performing
      extensive surgery. However, the ability to image with subcellular resolution in
      the intact animal enables a contextual setting that may be critical for
      understanding proper function. Clinical applications such as disease diagnosis
      and optical biopsy may benefit from minimally invasive in vivo approaches.
      Gradient index (GRIN) lenses with needle-like dimensions can transfer high
      quality images many centimeters from the object plane. Here, we show that
      multiphoton microscopy through GRIN lenses enables minimally invasive,
      subcellular resolution several millimeters in the anesthetized, intact animal,
      and we present in vivo images of cortical layer V and hippocampus in the
      anesthetized Thy1-YFP line H mouse. Microangiographies from deep capillaries and
      blood vessels containing fluorescein-dextran and quantum dot-labeled serum in
      wild-type mouse brain are also demonstrated.

PMID- 14668301
TI  - Localized IP3-evoked Ca2+ release activates a K+ current in primary vagal sensory
      neurons.
AB  - Electrophysiological and microfluorimetric techniques were used to determine
      whether intracellular photorelease of caged IP(3), and the consequent release of
      Ca(2+), could trigger a Ca(2+)-activated K(+) current (I(IP3)). Photorelease of
      caged IP(3) evoked an I(IP3) that averaged 2.36 +/- 0.35 (SE) pA/pF in 24 of 28
      rabbit primary vagal sensory neurons (nodose ganglion neurons, NGNs) voltage
      clamped at -50 mV. I(IP3) was abolished by intracellular BAPTA (2 mM), a Ca(2+)
      chelator. Changing the K(+) equilibrium potential by increasing extracellular
      K(+) ion concentration caused a predicted Nernstian shift in the reversal
      potential of I(IP3). These results indicated that I(IP3) was a Ca(2+)-dependent
      K(+) current. I(IP3) was unaffected by three common antagonists of Ca(2+)
      activated K(+) currents: bath-applied iberiotoxin (50 nM) or apamin (100 nM), and
      intracellular 8-Br-cAMP (100 microM) included in the patch pipette. We have
      previously demonstrated that both IP(3)-evoked Ca(2+) release and Ca(2+)-induced
      Ca(2+) release (CICR) are co-expressed in NGNs and that CICR can trigger a Ca(2+)
      activated K(+) current. In the present study, using caffeine, a CICR agonist, to
      selectively attenuate intracellular Ca(2+) stores, we showed that IP(3)-evoked
      Ca(2+) release occurs independently of CICR, but interestingly, that a component
      of I(IP3) requires CICR. These data suggest that IP(3)-evoked Ca(2+) release
      activates a K(+) current that is pharmacologically distinct from other Ca(2+)
      activated K(+) currents in NGNs. We describe several models that explain our
      results based on Ca(2+) signaling microdomains in NGNs.

PMID- 14668302
TI  - Synthesis of multiwhisker-receptive fields in subcortical stations of the
      vibrissa system.
AB  - This study addresses the origins of multiwhisker-receptive fields of neurons in
      the thalamic ventral posterior medial (VPM) nucleus of the rat. We sought to
      determine whether multiwhisker-receptive field synthesis occurs in VPM through
      convergent projections from the principalis (PrV) and interpolaris (SpVi) nuclei,
      or in PrV by intersubnuclear projections from the spinal trigeminal complex. We
      tested these hypotheses by recording whisker-evoked responses in PrV and VPM
      before and after electrolytic lesion of the SpVi in lightly anesthetized rats.
      Before the lesion PrV cells responded, on average, to 3.2 +/- 1.2 whiskers but
      responsiveness was reduced to 1.07 +/- 0.31 whisker after the lesion. A similar
      reduction of receptive field size was observed in VPM, where neurons responded,
      on average, to 2.94 +/- 0.95 whiskers before the lesion and to 1.05 +/- 0.22
      whisker after the lesion. Thus one can conclude that intersubnuclear projections
      mediate surround whisker-receptive fields in PrV, and therefore in VPM. However,
      it has previously been shown that parasagittal brain stem transection, which
      severed ascending projections from SpVi, but left intersubnuclear connections
      intact, rendered VPM cells monowhisker responsive. We wondered whether midline
      brain stem lesion modified receptive field properties in SpVi. In normal rats
      SpVi cells responded, on average, to 7.52 +/- 4.25 whiskers, but responsiveness
      was dramatically reduced to 1.47 +/- 1.07 whisker after the lesion. Together
      these results indicate that the synthesis of surround receptive fields in
      subcortical stations relies almost exclusively on intersubnuclear projections
      from the spinal trigeminal complex to the PrV.

PMID- 14668303
TI  - A Wigglesworth classic: how cells make patterns.

PMID- 14668304
TI  - Intrinsic autoregulation of cardiac output in rainbow trout (Oncorhynchus mykiss)
      at different heart rates.
AB  - Intrinsic regulation of the heart in teleosts is partly driven by central venous
      pressure, which exerts a modulatory role on stroke volume according to the well
      known Frank-Starling mechanism. Although this mechanism is well understood from
      heart perfusion studies, less is known about how this mechanism operates in vivo,
      where heart rate varies markedly. We used zatebradine, a bradycardic agent, to
      attain resting heart rates in surgically instrumented animals. A dose of
      zatebradine of 2.79+/-0.47 mg l(-1) decreased heart rate by half, from 44.4+/
      4.19 beats min(-1) to 22.1+/-1.9 beats min(-1). Zatebradine had no significant
      effect on the peripheral vasculature and no inotropic effects, so was a suitable
      pharmacological agent with which to manipulate heart rate. When heart rate
      halved, cardiac output dropped to 87.5+/-4.6% of the control value, due to the
      concomitant increase in stroke volume to 165+/-13%. In vivo recordings of venous
      pressure at varying heart rates indicated that the partial compensation in
      cardiac output was possible through an increase in pressure in the sinus venosus,
      from -0.06+/-0.04 kPa at a control heart rate of 58.3+/-3.5 beats min(-1) (N=10)
      to 0.07+/-0.05 kPa after injection of zatebradine (4 mg kg(-1)). The operation of
      the so-called time-dependent autoregulatory mechanism was further demonstrated in
      perfused hearts. The positive pressures recorded in the sinus venosus at low
      heart rates coincident with non-invasive measurements in trout suggest that
      atrial filling in trout is more dependent on the build-up of pressure in the
      venous circulation (vis-a-tergo filling) than a suction mechanism during
      ventricular contraction (vis-a-fronte filling).

PMID- 14668305
TI  - Partitioning of evaporative water loss in white-winged doves: plasticity in
      response to short-term thermal acclimation.
AB  - We investigated changes in the relative contributions of respiratory evaporative
      water loss (REWL) and cutaneous evaporative water loss (CEWL) to total
      evaporative water loss (TEWL) in response to short-term thermal acclimation in
      western white-winged doves Zenaida asiatica mearnsii. We measured REWL, CEWL,
      oxygen consumption and carbon dioxide production in a partitioned chamber using
      flow-through respirometry. In doves housed for 2-4 weeks in a room heated to ca.
      43 degrees C during the day, TEWL increased from 5.5+/-1.3 mg g(-1) h(-1) at an
      air temperature (T(a)) of 35 degrees C to 19.3+/-2.5 mg g(-1) h(-1) at T(a)=45
      degrees C. In doves housed at room temperature for the same period, TEWL
      increased from 4.6+/-1.1 mg g(-1) h(-1) at T(a)=35 degrees C to 16.1+/-4.6 mg g(
      1) h(-1) at T(a)=45 degrees C. The CEWL of heat-acclimated doves increased from
      3.6+/-1.2 mg g(-1) h(-1) (64% of TEWL) at 35 degrees C to 15.0+/-2.1 mg g(-1) h(
      1) (78% of TEWL) at T(a)=45 degrees C. Cool-acclimated doves exhibited more
      modest increases in CEWL, from 2.7+/-0.7 mg g(-1) h(-1) at T(a)=35 degrees C to
      7.8+/-3.4 mg g(-1) h(-1) at T(a)=45 degrees C, with the contribution of CEWL to
      TEWL averaging 53% over this T(a) range. Cool-acclimated doves became mildly
      hyperthermic (body temperature T(b)=42.9+/-0.4 degrees C) and expended 35% more
      energy relative to heat-acclimated doves (T(b)=41.9+/-0.6 degrees C) at T(a)=45
      degrees C, even though TEWL in the two groups was similar. In each of the two
      groups, metabolic rate did not vary with T(a), and averaged 7.1+/-0.5 mW g(-1) in
      cool-acclimated doves and 6.3+/-0.8 mW g(-1) in heat-acclimated doves. The
      differences in TEWL partitioning we observed between the two experimental groups
      resulted from a consistently lower skin water vapour diffusion resistance (r(v))
      in the heat-acclimated doves. At T(a)=45 degrees C, r(v) in the cool-acclimated
      doves was 120+/-81 s cm(-1), whereas r(v) in the heat-acclimated doves was 38+/-8
      s cm(-1). Our data reveal that in Z. a. mearnsii, TEWL partitioning varies in
      response to short-term thermal acclimation.

PMID- 14668306
TI  - Dynamics of leg muscle function in tammar wallabies (M. eugenii) during level
      versus incline hopping.
AB  - The goal of our study was to examine whether the in vivo force-length behavior,
      work and elastic energy savings of distal muscle-tendon units in the legs of
      tammar wallabies (Macropus eugenii) change during level versus incline hopping.
      To address this question, we obtained measurements of muscle activation (via
      electromyography), fascicle strain (via sonomicrometry) and muscle-tendon force
      (via tendon buckles) from the lateral gastrocnemius (LG) and plantaris (PL)
      muscles of tammar wallabies trained to hop on a level and an inclined (10
      degrees, 17.4% grade) treadmill at two speeds (3.3 m s(-1) and 4.2 m s(-1)).
      Similar patterns of muscle activation, force and fascicle strain were observed
      under both level and incline conditions. This also corresponded to similar
      patterns of limb timing and movement (duty factor, limb contact time and hopping
      frequency). During both level and incline hopping, the LG and PL exhibited
      patterns of fascicle stretch and shortening that yielded low levels of net
      fascicle strain [LG: level, -1.0+/-4.6% (mean +/- S.E.M.) vs incline, 0.6+/-4.5%;
      PL: level, 0.1+/-1.0% vs incline, 0.4+/-1.6%] and muscle work (LG: level, -8.4+/
      8.4 J kg(-1) muscle vs incline, -6.8+/-7.5 J kg(-1) muscle; PL: level, -2.0+/-0.6
      J kg(-1) muscle vs incline, -1.4+/-0.7 J kg(-1) muscle). Consequently, neither
      muscle significantly altered its contractile dynamics to do more work during
      incline hopping. Whereas electromyographic (EMG) phase, duration and intensity
      did not differ for the LG, the PL exhibited shorter but more intense periods of
      activation, together with reduced EMG phase (P<0.01), during incline versus level
      hopping. Our results indicate that design for spring-like tendon energy savings
      and economical muscle force generation is key for these two distal muscle-tendon
      units of the tammar wallaby, and the need to accommodate changes in work
      associated with level versus incline locomotion is achieved by more proximal
      muscles of the limb.

PMID- 14668307
TI  - Postprandial response of gastric pH in leopard sharks (Triakis semifasciata) and
      its use to study foraging ecology.
AB  - Changes in gastric pH of leopard sharks Triakis semifasciata were quantified as
      an indicator of feeding frequency and ration size. Continuous in situ
      measurements of gastric pH were made in captive adult leopard sharks using an
      autonomous pH/temperature probe for periods ranging from 5-16 days. Instrumented
      sharks were fed meals of squid at different ration sizes. Gastric fluid samples
      were also taken from non-instrumented juvenile leopard sharks at different time
      intervals after feeding, and the pH measured to quantify effects of the pH probe
      in the stomach. Continuous in situ measurements of pH show that empty stomachs
      have a low pH of 1.54+/-1.42 (mean +/- S.D.) and that feeding causes a rapid
      increase in pH to 3.11+/-0.71, followed by a gradual decrease back down to
      baseline levels. There was a positive relationship between changes in pH and meal
      size (r(2)=0.72, P=0.001). There were no significant differences in pH between
      continuous in situ and laboratory serial sample measurements. Together these
      findings indicate that gastric acid secretion may be continuous in leopard
      sharks, and that changes in gastric pH may be used to estimate feeding
      chronology, frequency and ration size of leopard sharks in the field.

PMID- 14668308
TI  - Locomotion of lizards on inclines and perches: hindlimb kinematics of an arboreal
      specialist and a terrestrial generalist.
AB  - Arboreal animals, especially lizards, often traverse three-dimensional networks
      of narrow perches with variable and steep inclines, but the effects of both
      incline and narrow surfaces on the locomotor movement and function of limbs are
      poorly understood. Thus, we quantified the three-dimensional hindlimb kinematics
      of a specialized arboreal lizard, Chamaeleo calyptratus, moving horizontally, and
      up and down a 30 degrees incline on a narrow (2.4 cm) perch and a flat surface.
      We compared the flat-surface data of C. calyptratus with those of an anatomically
      generalized terrestrial lizard, Dipsosaurus dorsalis. Inclines had significant
      main effects for relatively few kinematic variables of C. calyptratus (11%)
      compared to D. dorsalis (73%). For C. calyptratus, the main effects of locomotor
      surface were nearly three times more widespread than those of incline. The foot
      of C. calyptratus was markedly anterior to the hip at footfall, primarily as a
      result of an unusually extended knee for a lizard. A large amount of knee flexion
      during early stance may be used by C. calyptratus to actively pull the body
      forward in a manner not found in D. dorsalis. Unexpectedly, the pelvic rotation
      of C. calyptratus greatly exceeded that of D. dorsalis and, unlike D. dorsalis,
      was not affected by incline. The more medial location of the foot of C.
      calyptratus on the narrow perch during stance was primarily a result of knee
      flexion rather than femur depression. Unlike previous qualitative descriptions of
      chameleons, our data for the hindlimb posture of C. calyptratus during stance
      indicate that the limb was not particularly erect.

PMID- 14668309
TI  - In vivo muscle activity in the hindlimb of the arboreal lizard, Chamaeleo
      calyptratus: general patterns and the effects of incline.
AB  - Arboreal animals often move on surfaces with variable and steep inclines, but the
      changes in hindlimb muscle activity in response to incline are poorly understood.
      Thus, we studied the hindlimb muscle activity in the arboreal specialist,
      Chamaeleo calyptratus, moving up and down 45 degrees inclines and on a horizontal
      surface. We quantified electromyograms (EMGs) from nine hindlimb muscles, and
      correlated EMGs with three-dimensional hindlimb kinematics. Kinematics changed
      little with incline, but the EMGs changed substantially. Most of the changes in
      EMGs were for amplitude rather than timing, and the EMGs of the hip and thigh
      muscles had more conspicuous changes with incline than those of the lower limb
      muscles. Unlike most other vertebrates, chameleons flexed the knee substantially
      during the first half of stance while the foot was anchored to the perch, and the
      amplitude of two large knee flexors increased when moving uphill compared to
      level and downhill. Thus, knee flexion in early stance probably contributes
      significantly to propulsion in C. calyptratus. During stance, the caudofemoralis
      EMGs of C. calyptratus correlated well with femur retraction, knee flexion and
      posterior femur rotation, and their amplitudes were higher on uphill and level
      surfaces than on the downhill surface. During the second half of stance,
      iliotibialis EMGs correlated well with knee extension, and their amplitude was
      highest on the uphill surface and lowest on the downhill surface. Many of the
      muscles in the hindlimb of C. calyptratus changed activity with incline in a
      manner similar to the propulsive limb muscles in mammals. Although muscle strain
      often increases when animals need more power to move uphill, the minimal changes
      in the hindlimb kinematics of C. calyptratus with incline imply little change in
      muscle strain.

PMID- 14668310
TI  - Top-down regression of the avian oviduct during late oviposition in a small
      passerine bird.
AB  - Egg production in oviparous vertebrates is assumed to be costly but the
      physiological basis of any costs remains unknown. The avian oviduct is a highly
      differentiated linear organ, with five functionally specific regions. Here we
      show that the oviduct regresses rapidly "from the top down" as soon as the more
      proximal regions have completed their function but while the distal regions still
      retain an oviductal egg. In zebra finches Taeniopygia guttata, oviduct mass did
      not differ between early laying birds at the 1-egg stage compared with late
      laying birds (with one remaining yolky follicle; dry mass, 151-167 mg). However,
      in birds with no remaining yolky follicles but with an oviductal egg, oviduct
      mass decreased to 94 mg (44%). Regression occurred unequally among different
      regions of the oviduct, with significant decreases in the proximal
      infundibulum/magnum and isthmus regions (59% and 40%, respectively), but no
      change in distal shell gland/vagina mass. The shell gland did not regress until
      after the last oviposition. Thus, the avian oviduct has a highly regulated size
      function relationship consistent with a high maintenance energy cost for this
      organ. We suggest that oviduct function is a significant contributor to the
      physiological costs of egg production and might mediate individual variation in
      maternal effects associated with non-yolk components of egg quality (e.g.
      immunoglobulins, lysozyme).

PMID- 14668311
TI  - Alpha-adrenergic regulation of systemic peripheral resistance and blood flow
      distribution in the turtle Trachemys scripta during anoxic submergence at 5
      degrees C and 21 degrees C.
AB  - Anoxic exposure in the anoxia-tolerant freshwater turtle is attended by
      substantial decreases in heart rate and blood flows, but systemic blood pressure
      (P(sys)) only decreases marginally due to an increase in systemic peripheral
      resistance (R(sys)). Here, we investigate the role of the alpha-adrenergic system
      in modulating R(sys) during anoxia at 5 degrees C and 21 degrees C in the turtle
      Trachemys scripta, and also describe how anoxia affects relative systemic blood
      flow distribution (%.Q(sys)) and absolute tissue blood flows. Turtles were
      instrumented with an arterial cannula for measurement of P(sys) and ultrasonic
      flow probes on major systemic blood vessels for determination of systemic cardiac
      output ((.Qsys)). Alpha-adrenergic tone was assessed from vascular injections of
      alpha-adrenergic agonists and antagonists (phenylephrine and phentolamine,
      respectively) during normoxia and following either 6 h (21 degrees C) or 12 days
      (5 degrees C) of anoxic submergence. Coloured microspheres, injected through a
      left atrial cannula during normoxia and anoxia, as well as after alpha-adrenergic
      stimulation and blockade during anoxia at both temperatures, were used to
      determine relative and absolute tissue blood flows. Anoxia was associated with an
      increased R(sys) and functional alpha-adrenergic vasoactivity at both acclimation
      temperatures. However, while anoxia at 21 degrees C was associated with a high
      systemic alpha-adrenergic tone, the progressive increase of R(sys) at 5 degrees C
      was not mediated by alpha-adrenergic control. A redistribution of blood flow away
      from ancillary vascular beds towards more vital circulations occurred with anoxia
      at both acclimation temperatures. %.Q(sys) and absolute blood flow were reduced
      to the digestive and urogenital tissues (approximately 2- to 15-fold), while
      %.Q(sys) and absolute blood flows to the heart and brain were maintained at
      normoxic levels. The importance of liver and muscle glycogen stores in fueling
      anaerobic metabolism were indicated by increases in %.Q(sys) to the muscle at 21
      degrees C (1.3-fold) and liver at 5 degrees C (1.7-fold). As well, the crucial
      importance of the turtle shell as a buffer reserve during anoxic submergence was
      indicated by 40-50% of .Q(sys) being directed towards the shell during anoxia at
      both 5 degrees C and 21 degrees C. Alpha-adrenergic stimulation and blockade
      during anoxia caused few changes in %.Q(sys) and absolute tissue blood flow.
      However, there was evidence of alpha-adrenergic vasoactivity contributing to
      blood flow regulation to the liver and shell during anoxic submergence at 5
      degrees C.

PMID- 14668312
TI  - Are melanized feather barbs stronger?
AB  - Melanin has been associated with increased resistance to abrasion, decreased wear
      and lowered barb breakage in feathers. But, this association was inferred without
      considering barb position along the rachis as a potentially confounding variable.
      We examined the cross-sectional area, breaking force, breaking stress, breaking
      strain and toughness of melanized and unmelanized barbs along the entire rachis
      of a primary feather from an osprey (Pandion haliaetus). Although breaking force
      was higher for melanized barbs, breaking stress (force divided by cross-sectional
      area) was greater for unmelanized barbs. But when position was considered, all
      mechanical differences between melanized and unmelanized barbs disappeared. Barb
      breaking stress, breaking strain and toughness decreased, and breaking stiffness
      increased, distally along the rachis. These proximal-distal material property
      changes are small and seem unlikely to affect flight performance of barbs. Our
      observations of barb bending, breaking and morphology, however, lead us to
      propose a design principle for barbs. We propose that, by being thicker-walled
      dorso-ventrally, the barb's flexural stiffness is increased during flight; but,
      by allowing for twisting when loaded with dangerously high forces, barbs firstly
      avoid failure by bending and secondly avoid complete failure by buckling rather
      than rupturing.

PMID- 14668313
TI  - Cold-acclimation in Peromyscus: temporal effects and individual variation in
      maximum metabolism and ventilatory traits.
AB  - Thermal acclimation in small endotherms provides an excellent model for the study
      of physiological plasticity, as energy requirements can be easily manipulated and
      the results are relevant for natural conditions. Nevertheless, how physiology
      changes throughout acclimation, and how individuals vary in their response to
      acclimation, remain poorly understood. Here we describe a high temporal
      resolution study of cold acclimation in the deer mouse Peromyscus maniculatus.
      The experimental design was based on repeated measures at short intervals
      throughout cold acclimation, with controls (maintained at constant temperature)
      for measurement artifacts. We monitored body mass, maximum metabolic rate in cold
      exposure and ventilatory traits (respiratory frequency, tidal and minute volume
      and oxygen extraction) for 3 weeks at 23 degrees C. Then, half of the individuals
      were held for 7 weeks at 5 degrees C. Body mass was differently affected by cold
      acclimation depending on sex. Maximal metabolism ((O(2)max)) increased
      significantly during the first week of cold acclimation, "overshot" after 5 weeks
      and dropped to a plateau about 34% above control values at week 7. Similarly,
      ventilatory traits increased during cold acclimation, though responses were
      different in their kinetics and magnitude. Body mass, maximum metabolism, and
      most ventilatory traits were repeatable after 7 weeks in control and cold
      acclimated animals. However, repeatability tended to be lower in the cold
      acclimated group, especially while animals were still acclimating. Our results
      show that acclimation effects may be under- and/or overestimated, depending on
      when trials are performed, and that different traits respond differently, and at
      different rates, to acclimation. Hence, future studies should be designed to
      ensure that animals have attained steady-state values in acclimation experiments.

PMID- 14668314
TI  - Seasonal metabolic depression, substrate utilisation and changes in scaling
      patterns during the first year cycle of tegu lizards (Tupinambis merianae).
AB  - The tegus increase in body mass after hatching until early autumn, when the
      energy intake becomes gradually reduced. Resting rates of oxygen consumption in
      winter drop to 20% of the values in the active season ((O(2))=0.0636 ml g(-1) h(
      1)) and are nearly temperature insensitive over the range of 17-25 degrees C
      (Q(10)=1.55). During dormancy, plasma glucose levels are 60% lower than those in
      active animals, while total protein, total lipids and beta-hydroxybutyrate are
      elevated by 24%, 43% and 113%, respectively. In addition, a significant depletion
      of liver carbohydrate (50%) and of fat deposited in the visceral fat bodies (24%)
      and in the tail (25%) and a slight loss of skeletal muscle protein (14%) were
      measured halfway through the inactive period. Otherwise, glycogen content is
      increased 4-fold in the brain and 2.3-fold in the heart of dormant lizards,
      declining by the onset of arousal. During early arousal, the young tegus are
      still anorexic, although (O(2)) is significantly greater than winter rates. The
      fat deposits analysed are further reduced (62% and 45%, respectively) and there
      is a large decrease in tail muscle protein (50%) together with a significant
      increase in glycogen (2-3-fold) and an increase in plasma glucose (40%), which
      suggests a role for gluconeogenesis as a supplementary energy source in arousing
      animals. No change is detectable in citrate synthase activity, but beta
      hydroxyacyl CoA dehydrogenase activities are strongly affected by season,
      reaching a 3-fold and 5-fold increase in the liver tissue of winter and arousing
      animals, respectively, and becoming reduced by half in skeletal muscle and heart
      of winter animals compared with late fall or spring active individuals. From
      hatching to late autumn, the increase of the fat body mass relatively to body
      mass is disproportionate (b=1.44), and the mass exponent changes significantly to
      close to 1.0 during the fasting period. The concomitant shift in the (O(2)) mass
      exponent in early autumn (b=0.75) to values significantly greater than 1.0 in
      late autumn and during winter dormancy indicates an allometric effect on the
      degree of metabolic depression related to the size of the fat stores and suggests
      greater energy conservation in the smaller young.

PMID- 14668315
TI  - Adaptive function of soil consumption: an in vitro study modeling the human
      stomach and small intestine.
AB  - Despite occurring in a wide variety of taxa, deliberate soil consumption
      (geophagy) is a poorly understood behavior. In humans, geophagy is sometimes
      considered aberrant or a sign of metabolic dysfunction. However, geophagy is
      normally assigned an adaptive function in nonhuman primates and various other
      organisms. One hypothesis submits that clay-rich soil adsorbs intestinal insults,
      namely plant metabolites or diarrhoea-causing enterotoxins. Here we test the
      capacity of kaolin, a commonly ingested clay, to adsorb quinine (an alkaloid) and
      two types of tannin (digestion-inhibitors). Trials were conducted in vitro using
      the TNO Intestinal Model, a device that closely simulates digestion by the human
      stomach and small intestine. Kaolin reduced the bioavailability of each compound
      by < or =30%. However, because we could not replicate clay-epithelial adhesion
      and reduced motility, these results may underestimate adsorption in vivo. We also
      show that kaolin fails to render calcium oxalate soluble. We conclude that
      gastrointestinal adsorption is the most plausible function of human geophagy.
      Adaptive advantages include greater exploitation of marginal plant foods and
      reduced energetic costs of diarrhoea, factors that could account for the high
      frequency of geophagy in children and pregnant women across the tropics.

PMID- 14668316
TI  - Ontogeny of osmoregulatory structures and functions in the green crab Carcinus
      maenas (Crustacea, Decapoda).
AB  - The ontogeny of osmoregulation, the development of branchial transporting
      epithelia and the expression of the enzyme Na+/K+-ATPase were studied in Carcinus
      maenas (L.) obtained from the North Sea, Germany. Laboratory-reared zoea larvae,
      megalopae and young crabs were exposed to a wide range of salinities, and
      hemolymph osmolality was measured after 24 h exposure time (72 h in juveniles).
      Zoea I larvae slightly hyper-regulated in dilute media (10.2 per thousand and
      17.0 per thousand ) and osmoconformed at >17 per thousand. All later zoeal stages
      (II-IV) osmoconformed in salinities from 10.2 per thousand to 44.3 per thousand.
      The megalopa hyper-regulated at salinities from 10.2 to 25.5 per thousand. Young
      crabs hyperregulated at salinities from 5.3 per thousand to 25.5 per thousand,
      showing an increase in their osmoregulatory capacity. The development of
      transporting epithelia and the expression of Na+/K+-ATPase were investigated by
      means of transmission electron microscopy and immunofluorescence microscopy. In
      the zoea IV, only a very light fluorescence staining was observed in gill buds.
      Epithelial cells were rather undifferentiated, without showing any features of
      ionocytes. Gills were present in the megalopa, where Na+/K+-ATPase was located in
      basal filaments of the posterior gills. In crab I juveniles and adults, Na+/K+
      ATPase was noted in the three most posterior pairs of gills, but lacking in
      anterior gills. Ionocytes could first be recognized in filaments of megalopal
      posterior gills, persisting through subsequent stages at the same location. Thus,
      the development of the gills and the expression of Na+/K+-ATPase are closely
      correlated with the ontogeny of osmoregulatory abilities. The morphological two
      step metamorphosis of C. maenas can also be regarded as an osmo-physiological
      metamorphosis, (i) from the osmoconforming zoeal stages to the weakly regulating
      megalopa, and (ii) to the effectively hyper-regulating juvenile and adult crabs.

PMID- 14668317
TI  - Acclimation of sperm motility apparatus in seawater-acclimated euryhaline tilapia
      Oreochromis mossambicus.
AB  - Euryhaline tilapia Oreochromis mossambicus can reproduce in freshwater and in
      seawater. Regulation of sperm motility appears to be modulated during acclimation
      of the fish from freshwater to seawater, being independent of extracellular Ca2+
      in freshwater and dependent on extracellular Ca2+ in seawater. In the presence of
      extracellular Ca2+, sperm of seawater-acclimated tilapia (SWT) showed motility
      even in a hypertonic environment, whereas sperm of freshwater-acclimated tilapia
      (FWT) were not motile. The Ca2+ indicator, fluo-3, revealed that intracellular
      Ca2+ concentration, [Ca2+]i, of SWT sperm increased only in the presence of
      extracellular Ca(2+) in hypotonic or hypertonic conditions. Since the increased
      [Ca2+]i in FWT sperm occurred under hypotonic conditions via intracellular Ca2+
      stores, it is likely that tilapia modulate their source of increasing [Ca2+]i
      from intracellular stores (in FWT sperm) to extracellular stores (in SWT sperm).
      Experiments using demembranated sperm revealed that Ca2+ is necessary for
      activation of motility, suggesting that Ca2+ plays a key role in motility
      regulation in SWT sperm. We detected three phosphoproteins associated with the
      activation of sperm motility. Serine and threonine residues of two proteins of 15
      kDa and 18 kDa became dephosphorylated in hypotonic conditions but remained
      phosphorylated in hypertonic conditions, suggesting that these protein
      phosphorylations were not only related to motility activation under hypertonic
      conditions but also resistant to osmotic pressure. The threonine residue(s) of a
      41 kDa protein was also phosphorylated in dry sperm, even in FWT sperm in
      motility-feasible hypotonic conditions. It is likely that acclimation of the
      motility apparatus is associated with modulation of the flow of Ca2+ to increase
      [Ca2+]i and protein phosphorylation.

PMID- 14668318
TI  - A facilitative urea transporter is localized in the renal collecting tubule of
      the dogfish Triakis scyllia.
AB  - Reabsorption of filtered urea by the kidney tubule is essential for retaining
      high levels of urea in body fluids of marine elasmobranchs. To elucidate the
      mechanisms of urea reabsorption, we examined the distribution of a facilitative
      urea transporter (UT) in the kidney of the dogfish Triakis scyllia. We isolated a
      cDNA encoding a UT that is homologous to the facilitative UT cloned from another
      dogfish species, Squalus acanthias. The Triakis UT mRNA is abundantly expressed
      in the kidney, while low levels of expression were detected in the brain and
      liver. In the dogfish kidney, each nephron makes four turns and traverses
      repeatedly between bundle zone and sinus zone. In the bundle zone, the resulting
      five tubular segments are arranged in a countercurrent loop fashion.
      Immunohistochemistry using specific antibodies raised against the cloned UT
      revealed that, among the nephron segments, the UT is expressed exclusively in the
      final segment of the bundle zone, i.e. in the collecting tubule of the Triakis
      kidney. In contrast to the limited localization of UT, the transport enzyme
      Na+/K+-ATPase is distributed in the basolateral membrane of numerous tubular
      segments both in the sinus zone and the bundle zone. However, in the collecting
      tubule, Na+/K+-ATPase immunoreactivity was not detected. The present study
      suggests that the collecting tubule is responsible for the reabsorption of urea
      in the marine elasmobranch kidney. Other countercurrent segments may contribute
      to production of a driving force for facilitative diffusion of urea through the
      UT.

PMID- 14668319
TI  - Seasonality of the red blood cell stress response in rainbow trout (Oncorhynchus
      mykiss).
AB  - The beta-adrenergic stress response in red blood cells (RBCs) of rainbow trout
      shows seasonal changes in expression. We have explored the mechanisms
      underpinning this response by following, over a period of 27 months, changes in
      beta-adrenergic receptor (beta-AR) binding characteristics, beta-adrenergically
      stimulated RBC Na(+)/H(+) exchanger (betaNHE) activity, together with beta-AR and
      betaNHE mRNA levels and plasma steroid hormone and lactate levels. These
      parameters were measured at approximately monthly intervals in a single
      population of fish held under semi-natural conditions. Membrane-bound, high
      affinity beta-ARs were present in RBCs at all sampling times, varying from 668+/
      112 receptors cell(-1) to 2654+/-882 receptors cell(-1) (mean +/- S.E.M.; N=8).
      betaNHE activity, however, was reduced by 57% and 34% in December 1999 and
      February 2001, respectively, compared with an otherwise sustained influx that
      averaged 110.4+/-2.3 mmol l(-1) RBCs h(-1) (N=119). Only one reduction coincided
      with a spawning period but both were preceded by transient increases in
      circulating testosterone. betaNHE activity measured under standard conditions was
      not correlated with the number or affinity of beta-ARs nor with water
      temperature, but both beta-AR numbers and betaNHE activity were positively
      related to their respective mRNA levels (P=0.005 and 0.038, respectively).
      Pharmaceutical intervention in the transduction cascade linking the beta-AR and
      betaNHE failed to indicate any failure of the transduction elements in RBCs
      displaying low betaNHE activity. Similarly, we failed to demonstrate any link
      between seasonal cortisol fluctuations and seasonally reduced betaNHE activity.
      However, the betaNHE activity of age-separated RBC fractions showed that younger
      RBCs had a significantly higher betaNHE response than older RBCs, consistent with
      the seasonal reductions in betaNHE being linked to turnover of RBCs and
      erythropoiesis. Testosterone is known to induce erythropoiesis and we conclude
      that seasonal reductions in betaNHE are not caused by changes in beta-AR numbers
      but may be linked to testosterone-induced erythropoiesis.

PMID- 14668320
TI  - Antennal movements reveal associative learning in the American cockroach
      Periplaneta americana.
AB  - Using antennal movements as an indicator of learning and retention, an
      associative learning paradigm has been developed to investigate associative
      memory between visual and olfactory stimuli. Experiments were performed on the
      restrained cockroach Periplaneta americana, which normally moves its antennae
      towards a localized odor source. Such "antennal projection responses" (APRs) are
      exploited to demonstrate long-term memory, where an APR is elicited by a
      conditioned stimulus (CS; green light point source) paired with a spatially
      coincident odor [the unconditioned stimulus (US)]. Association of the CS with the
      US is established after five trials. Before training, a visual cue alone does not
      elicit an APR. This behavior is elicited by a visual cue only after pairing it
      with an odor stimulus. The acquired APR to the green light cue persists for up to
      72 h, indicative of long-term memory. This paradigm is thus suitable for future
      studies of neural correlates of learning and memory on restrained animals.

PMID- 14668321
TI  - Spatial learning in the restrained American cockroach Periplaneta americana.
AB  - Spatial learning abilities were tested in restrained cockroaches by observing
      antennal projection responses towards the positions of a learned visual cue
      perceived monocularly by one eye in the context of a second stimulus provided to
      the contralateral eye. Memory of the position of the conditioning stimulus
      relative to the contralateral reference stimulus was tested by altering the
      relative positions of the two stimuli. Memory of the conditioning stimulus is
      retained if the angle between the conditioning stimulus and the contralateral
      reference stimulus is maintained. The results suggest that during learning the
      insect recognizes spatial relationships between the conditioning stimulus and the
      contralateral reference stimulus. Possible mechanisms, such as retinotopic
      matching versus angular matching, are discussed.

PMID- 14668322
TI  - Crystal structures of phosphodiesterases 4 and 5 in complex with inhibitor 3
      isobutyl-1-methylxanthine suggest a conformation determinant of inhibitor
      selectivity.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes
      controlling cellular concentrations of the second messengers cAMP and cGMP.
      Crystal structures of the catalytic domains of cGMP-specific PDE5A1 and cAMP
      specific PDE4D2 in complex with the nonselective inhibitor 3-isobutyl-1
      methylxanthine have been determined at medium resolution. The catalytic domain of
      PDE5A1 has the same topological folding as that of PDE4D2, but three regions show
      different tertiary structures, including residues 79-113, 208-224 (H-loop), and
      341-364 (M-loop) in PDE4D2 or 535-566, 661-676, and 787-812 in PDE5A1,
      respectively. Because H- and M-loops are involved in binding of the selective
      inhibitors, the different conformations of the loops, thus the distinct shapes of
      the active sites, will be a determinant of inhibitor selectivity in PDEs. IBMX
      binds to a subpocket that comprises key residues Ile-336, Phe-340, Gln-369, and
      Phe-372 of PDE4D2 or Val-782, Phe-786, Gln-817, and Phe-820 of PDE5A1. This
      subpocket may be a common site for binding nonselective inhibitors of PDEs.

PMID- 14668323
TI  - Inhibition of HIV-1 replication by cell-penetrating peptides binding Rev.
AB  - New therapeutic agents able to block HIV-1 replication are eagerly sought after
      to increase the possibilities of treatment of resistant viral strains. In this
      report, we describe a rational strategy to identify small peptide sequences
      owning the dual property of penetrating within lymphocytes and of binding to a
      protein target. Such sequences were identified for two important HIV-1 regulatory
      proteins, Tat and Rev. Their association to a stabilizing domain consisting of
      human small ubiquitin-related modifier-1 (SUMO-1) allowed the generation of small
      proteins named SUMO-1 heptapeptide protein transduction domain for binding Tat
      (SHPT) and SUMO-1 heptapeptide protein transduction domain for binding Rev
      (SHPR), which are stable and efficiently penetrate within primary lymphocytes.
      Analysis of the antiviral activity of these proteins showed that one SHPR is
      active in both primary lymphocytes and macrophages, whereas one SHPT is active
      only in the latter cells. These proteins may represent prototypes of new
      therapeutic agents targeting the crucial functions exerted by both viral
      regulatory factors.

PMID- 14668324
TI  - Novel roles of retinoid X receptor (RXR) and RXR ligand in dynamically modulating
      the activity of the thyroid hormone receptor/RXR heterodimer.
AB  - Many members of the type II nuclear receptor subfamily function as heterodimers
      with the retinoid X receptor (RXR). A permissive heterodimer (e.g. peroxisome
      proliferator-activated receptor/RXR) allows for ligand binding by both partners
      of the receptor complex. In contrast, RXR has been thought to be incapable of
      ligand binding in a nonpermissive heterodimer, such as that of thyroid hormone
      receptor (TR)/RXR, where it has been referred to as a silent partner. However, we
      recently presented functional evidence suggesting that RXR in the TR/RXR
      heterodimer can bind its natural ligand 9-cis-RA in cells. Here we extended our
      study of the interrelationship of TR and RXR. We examined the potential
      modulatory effect of RXR and its ligand on the activity of TR, primarily using a
      Gal4-TR chimera. This study led to several novel and unexpected findings: 1)
      heterodimerization of apo-RXRalpha (in the absence of 9-cis-RA) with Gal4-TR
      inhibits T3-mediated transactivation; 2) the inhibition of Gal4-TR activity by
      RXRalpha is further enhanced by 9-cis-RA; 3) two different RXR subtypes (alpha
      and beta) differentially modulate the activity of Gal4-TR; 4) the N-terminal A/B
      domains of RXR alpha and beta are largely responsible for their differential
      modulation of TR activity; and 5) the RXR ligand 9-cis-RA appears to
      differentially affect T3-mediated transactivation from the Gal4-TR/RXRalpha
      (which is inhibited by 9-cis-RA) and TRE-bound TR/RXRalpha (which is further
      activated by 9-cis-RA) heterodimers. Taken together, these results further
      support our recent proposal that the RXR component in a TR/RXR heterodimer is not
      silent and, more importantly, reveal novel aspects of regulation of the activity
      of the TR/RXR heterodimer by RXR and RXR ligand.

PMID- 14668325
TI  - Peroxisome proliferator-activated receptor gamma ligands regulate myeloperoxidase
      expression in macrophages by an estrogen-dependent mechanism involving the -463GA
      promoter polymorphism.
AB  - A functional myeloperoxidase (MPO) promoter polymorphism, -463GA, has been
      associated with incidence or severity of inflammatory diseases, including
      atherosclerosis and Alzheimer's disease, and some cancers. The polymorphism is
      within an Alu element encoding four hexamer repeats recognized by nuclear
      receptors (AluRRE). Here we show that peroxisome proliferator-activated receptor
      gamma (PPARgamma) agonists strongly regulate MPO gene expression through the
      AluRRE. Opposite effects were observed in granulocyte/macrophage colony
      stimulating factor (GMCSF)- versus macrophage colony-stimulating factor (MCSF)
      derived macrophages (Mphi): Expression was markedly up-regulated (mean 26-fold)
      in MCSF-Mphi and down-regulated (34-fold) in GMCSF-Mphi. This was observed with
      rosiglitazone and three other PPARgamma ligands of the thiazolidinedione class,
      as well as the natural prostaglandin metabolite 15-deoxy-Delta(12,14)
      prostaglandin J(2). The selective PPARgamma antagonist, GW9662, blocked both the
      positive and negative effects on MPO expression. Gel retardation assays showed
      PPARgamma bound hexamers 3/4, and estrogen receptor-alpha bound hexamers 1/2,
      with -463A in hexamer 1 enhancing binding. Estrogen blocked PPARgamma effects on
      MPO expression, especially for the A allele. Charcoal filtration of fetal calf
      serum eliminated the block of PPARgamma, whereas replenishing the medium with
      17beta-estradiol reinstated the block. These findings suggest a model in which
      estrogen receptor binds the AluRRE, preventing PPARgamma binding to the adjacent
      site. The positive and negative regulation by PPARgamma ligands, and the block by
      estrogen, was also observed in transgenic mice expressing the G and A alleles.
      The mouse MPO gene, which lacks the primate-specific AluRRE, was unresponsive to
      PPARgamma ligands, suggesting the human MPO transgenes will enhance the utility
      of mouse models for diseases involving MPO, such as atherosclerosis and
      Alzheimer's.

PMID- 14668326
TI  - Enhanced binding of TonB to a ligand-loaded outer membrane receptor: role of the
      oligomeric state of TonB in formation of a functional FhuA.TonB complex.
AB  - The ferric hydroxymate uptake (FhuA) receptor from Escherichia coli facilitates
      transport of siderophores ferricrocin and ferrichrome and siderophore-antibiotic
      conjugates such as albomycin and rifamycin CGP 4832. FhuA is also the receptor
      for phages T5, T1, Phi80, UC-1, for colicin M and for the antimicrobial peptide
      microcin MccJ21. Energy for transport is provided by the cytoplasmic membrane
      complex TonB.ExbB.ExbD, which uses the proton motive force of the cytoplasmic
      membrane to transduce energy to the outer membrane. To accomplish energy
      transfer, TonB contacts outer membrane receptors. However, the stoichiometry of
      TonB. receptor complexes and their sites of interaction remain uncertain. In this
      study, analyses of FhuA interactions with two recombinant TonB proteins by
      analytical ultracentrifugation revealed that TonB forms a 2:1 complex with FhuA.
      The presence of the FhuA-specific ligand ferricrocin enhanced the amounts of
      complex but is not essential for its formation. Surface plasmon resonance
      experiments demonstrated that FhuA.TonB interactions are multiple and have
      apparent affinities in the nanomolar range. TonB also possesses two distinct
      binding regions: one in the C terminus of the protein, for which binding to FhuA
      is ferricrocin-independent, and a higher affinity region outside the C terminus,
      for which ferricrocin enhances interactions with FhuA. Together these experiments
      establish that FhuA.TonB interactions are more intricate than originally
      predicted, that the TonB.FhuA stoichiometry is 2:1, and that ferricrocin
      modulates binding of FhuA to TonB at regions outside the C-terminal domain of
      TonB.

PMID- 14668327
TI  - Modification of ligand-independent B cell receptor tonic signals activates
      receptor editing in immature B lymphocytes.
AB  - Maturation of B lymphocytes strictly depends on the signaling competence of the B
      cell antigen receptor (BCR). Autoreactive receptors undergo negative selection
      and can be replaced by receptor editing. In addition, the process of maturation
      of non-self B cells and migration to the spleen, referred to as positive
      selection, is limited by the signaling competence of the BCR. Using 3-83Tg mice
      deficient of CD19 we have shown that signaling incompetence not only blocks
      positive selection but also activates receptor editing. Here we study the role of
      ligand-independent BCR tonic tyrosine phosphorylation signals in activation of
      receptor editing. We find that editing, immature 3-83Tg B cells deficient of CD19
      have elevated BCR tonic signals and that lowering these tonic signals effectively
      suppresses receptor editing. Furthermore, we show that elevation of BCR tonic
      signals in non-editing, immature 3-83Tg B cells stimulates significant receptor
      editing. We also show that positive selection and developmental progression from
      the bone marrow to the spleen are limited to cells capable of establishing
      appropriate tonic signals, as in contrast to immature cells, splenic 3-83Tg B
      cells deficient of CD19 have BCR tonic signals similar to those of the control 3
      83Tg cells. This developmental progression is accompanied by activation of
      molecules signaling for growth and survival. Hence, we suggest that ligand
      independent BCR tonic signals are required for promoting positive selection and
      suppressing the receptor-editing mechanism in immature B cells.

PMID- 14668328
TI  - The mechanisms by which family 10 glycoside hydrolases bind decorated substrates.
AB  - Endo-beta-1,4-xylanases (xylanases), which cleave beta-1,4 glycosidic bonds in
      the xylan backbone, are important components of the repertoire of enzymes that
      catalyze plant cell wall degradation. The mechanism by which these enzymes are
      able to hydrolyze a range of decorated xylans remains unclear. Here we reveal the
      three-dimensional structure, determined by x-ray crystallography, and the
      catalytic properties of the Cellvibrio mixtus enzyme Xyn10B (CmXyn10B), the most
      active GH10 xylanase described to date. The crystal structure of the enzyme in
      complex with xylopentaose reveals that at the +1 subsite the xylose moiety is
      sandwiched between hydrophobic residues, which is likely to mediate tighter
      binding than in other GH10 xylanases. The crystal structure of the xylanase in
      complex with a range of decorated xylooligosaccharides reveals how this enzyme is
      able to hydrolyze substituted xylan. Solvent exposure of the O-2 groups of xylose
      at the +4, +3, +1, and -3 subsites may allow accommodation of the alpha-1,2
      linked 4-O-methyl-d-glucuronic acid side chain in glucuronoxylan at these
      locations. Furthermore, the uronic acid makes hydrogen bonds and hydrophobic
      interactions with the enzyme at the +1 subsite, indicating that the sugar
      decorations in glucuronoxylan are targeted to this proximal aglycone binding
      site. Accommodation of 3'-linked l-arabinofuranoside decorations is observed in
      the -2 subsite and could, most likely, be tolerated when bound to xylosides in -3
      and +4. A notable feature of the binding mode of decorated substrates is the way
      in which the subsite specificities are tailored both to prevent the formation of
      "dead-end" reaction products and to facilitate synergy with the xylan degradation
      accessory enzymes such as alpha-glucuronidase. The data described in this report
      and in the accompanying paper indicate that the complementarity in the binding of
      decorated substrates between the glycone and aglycone regions appears to be a
      conserved feature of GH10 xylanases.

PMID- 14668329
TI  - Bcl-3 and NFkappaB p50-p50 homodimers act as transcriptional repressors in
      tolerant CD4+ T cells.
AB  - The transcriptional events that control T cell tolerance are still poorly
      understood. To investigate why tolerant T cells fail to produce interleukin (IL)
      2, we analyzed the regulation of NFkappaB-mediated transcription in CD4(+) T
      cells after tolerance induction in vivo. We demonstrate that a predominance of
      p50-p50 homodimers binding to the IL-2 promoter kappaB site in tolerant T cells
      correlated with repression of NFkappaB-driven transcription. Impaired
      translocation of the p65 subunit in tolerant T cells was a result from reduced
      activation of IkappaB kinase and poor phosphorylation and degradation of
      cytosolic IkappaBs. Moreover, tolerant T cells expressed high amounts of the p50
      protein. However, the increased expression of p50 could not be explained by
      activation-induced de novo synthesis of the precursor p105, which was
      constitutively expressed in tolerant T cells. We also demonstrate the exclusive
      induction of the IkappaB protein B cell lymphoma 3 (Bcl-3) in tolerant T cells as
      well as its specific binding to the NFkappaB site. These results suggest that the
      cellular ratio of NFkappaB dimers, and thus the repression of NFkappaB activity
      and IL-2 production, are regulated at several levels in tolerant CD4(+) T cells
      in vivo.

PMID- 14668330
TI  - Ammonium sensing in Escherichia coli. Role of the ammonium transporter AmtB and
      AmtB-GlnK complex formation.
AB  - The Amt proteins are high affinity ammonium transporters that are conserved in
      all domains of life. In bacteria and archaea the Amt structural genes (amtB) are
      invariably linked to glnK, which encodes a member of the P(II) signal
      transduction protein family, proteins that regulate many facets of nitrogen
      metabolism. We have now shown that Escherichia coli AmtB is inactivated by
      formation of a membrane-bound complex with GlnK. Complex formation is reversible
      and occurs within seconds in response to micromolar changes in the extracellular
      ammonium concentration. Regulation is mediated by the
      uridylylation/deuridylylation of GlnK in direct response to fluctuations in the
      intracellular glutamine pool. Furthermore under physiological conditions AmtB
      activity is required for GlnK deuridylylation. Hence the transporter is an
      integral part of the signal transduction cascade, and AmtB can be formally
      considered to act as an ammonium sensor. This system provides an exquisitely
      sensitive mechanism to control ammonium flux into the cell, and the conservation
      of glnK linkage to amtB suggests that this regulatory mechanism may occur
      throughout prokaryotes.

PMID- 14668331
TI  - The prion curing agent guanidinium chloride specifically inhibits ATP hydrolysis
      by Hsp104.
AB  - The molecular chaperone Hsp104 from Saccharomyces cerevisiae dissolves protein
      aggregates in the cell and is thus of crucial importance for the thermotolerance
      of yeast. In addition to this disaggregase activity, Hsp104 has a key function in
      yeast prion propagation, as Hsp104 was found to be essential for the maintenance
      of the associated phenotypes. In vivo data suggest that Hsp104 function is
      affected by guanidinium chloride. Adding small amounts of this compound to yeast
      medium causes curing of the prions: cells lose their prion-related phenotype.
      Guanidinium chloride was also found to impair heat shock resistance. Here, we
      present a detailed in vitro analysis showing that guanidinium chloride is an
      uncompetitive inhibitor of Hsp104. Micromolar concentrations of this agent reduce
      the ATPase activity of Hsp104 to approximately 35% of its normal activity. This
      inhibition is not related to the denaturing properties of this compound, because
      Hsp104 was not affected by urea. Guanidinium ions selectively bind to the
      nucleotide-bound, hexameric state of the molecular chaperone. Thus, they increase
      the affinity of Hsp104 for adenine nucleotides and promote the nucleotide
      dependent oligomerization of the chaperone. Our findings strongly suggest that
      guanidinium chloride causes curing of yeast prions by perturbing the ATPase of
      Hsp104, which is essential for both prion propagation and thermotolerance.

PMID- 14668332
TI  - Mechanism of chorismate synthase. Role of the two invariant histidine residues in
      the active site.
AB  - Chorismate synthase catalyzes the last step in the common shikimate pathway
      leading to aromatic compounds such as the aromatic amino acids. The reaction
      consists of the 1,4-anti-elimination of the 3-phosphate group and the C-(6proR)
      hydrogen from 5-enolpyruvylshikimate 3-phosphate to yield chorismate. Although
      this reaction does not involve a net redox change, the enzyme has an absolute
      requirement for reduced flavin mononucleotide, which is not consumed during the
      reaction. Two invariant histidine residues are found in the active site of the
      enzyme: His(17) and His(106). Using site-directed mutagenesis, both histidines
      were replaced by alanine, reducing the activity 10- and 20-fold in the H106A and
      H17A mutant protein, respectively. Based on the characterization of the two
      single mutant proteins, it is proposed that His(106) serves to protonate the
      monoanionic reduced FMN, whereas His(17) protonates the leaving phosphate group
      of the substrate. An enzymatic reaction mechanism in keeping with the
      experimental results is presented.

PMID- 14668333
TI  - Janus kinase 2 modulates the apolipoprotein interactions with ABCA1 required for
      removing cellular cholesterol.
AB  - ATP-binding cassette transporter A1 (ABCA1) mediates transport of cellular
      cholesterol and phospholipids to high density lipoprotein (HDL) apolipoproteins,
      such as apoA-I. ABCA1 mutations can cause a severe HDL deficiency and
      atherosclerosis. Here we show that the protein-tyrosine kinase (TK) Janus kinase
      2 (JAK2) modulates the apolipoprotein interactions with ABCA1 required for
      removing cellular lipids. The protein kinase A (PKA) inhibitor H89, the TK
      inhibitor genistein, and the JAK2 inhibitor AG490 suppressed apoA-I-mediated
      cholesterol and phospholipid efflux from ABCA1-expressing cells without altering
      the membrane ABCA1 content. Whereas PKA inhibition had no effect on apoA-I
      binding to cells or to ABCA1, TK and JAK2 inhibition greatly reduced these
      activities. Conversely, PKA but not JAK2 inhibition significantly reduced the
      intrinsic cholesterol translocase activity of ABCA1. Mutant cells lacking JAK2
      had a severely impaired apoA-I-mediated cholesterol and phospholipid efflux and
      apoA-I binding despite normal ABCA1 protein levels and near normal cholesterol
      translocase activity. Thus, although PKA modulates ABCA1 lipid transport
      activity, JAK2 appears to selectively modulate apolipoprotein interactions with
      ABCA1. TK-mediated phosphorylation of ABCA1 was undetectable, implicating the
      involvement of another JAK2-targeted protein. Acute incubation of ABCA1
      expressing cells with apoA-I had no effect on ABCA1 phosphorylation but
      stimulated JAK2 autophosphorylation. These results suggest that the interaction
      of apolipoproteins with ABCA1-expressing cells activates JAK2, which in turn
      activates a process that enhances apolipoprotein interactions with ABCA1 and
      lipid removal from cells.

PMID- 14668334
TI  - The Schizosaccharomyces pombe corepressor Tup11 interacts with the iron
      responsive transcription factor Fep1.
AB  - The Schizosaccharomyces pombe fep1(+) gene encodes a GATA transcription factor
      that represses the expression of iron transport genes in response to elevated
      iron concentrations. This transcriptional response is altered only in strains
      harboring a combined deletion of both tup11(+) and tup12(+) genes. This suggests
      that Tup11 is capable of negatively regulating iron transport gene expression in
      the absence of Tup12 and vice versa. The tup11(+)- and tup12(+)-encoded proteins
      resemble the Saccharomyces cerevisiae Tup1 corepressor. Using yeast two-hybrid
      analysis we show that Tup11 and Fep1 physically interact with each other. The C
      terminal region from amino acids 242 to 564 of Fep1 is required for interaction
      with Tup11. Within this region, a minimal domain encompassing amino acids 405-541
      was sufficient for Tup11-Fep1 association. Deletion mapping analysis revealed
      that the WD40-repeat sequence motifs of Tup11 are necessary for its interaction
      with Fep1. Analysis of Tup11 mutants with single amino acid substitutions in the
      WD40 repeats suggested that the Fep1 transcription factor interacts with a
      putative flat upper surface on the predicted beta-propeller structure of this
      motif. Further analysis by in vivo coimmunoprecipitation showed that Tup11 and
      Fep1 are physically associated. In vitro pull-down experiments further verified a
      direct interaction between the Fep1 C terminus and the Tup11 C-terminal WD40
      repeat domain. Taken together, these results describe the first example of a
      physical interaction between a corepressor and an iron-sensing factor controlling
      the expression of iron uptake genes.

PMID- 14668335
TI  - Observation and characterization of the interaction between a single
      immunoglobulin binding domain of protein L and two equivalents of human kappa
      light chains.
AB  - Detailed stopped-flow studies in combination with site-directed mutagenesis,
      isothermal titration calorimetry data and x-ray crystallographic knowledge have
      revealed that the biphasic pre-equilibrium fluorescence changes reported for a
      single Ig-binding domain of protein L from Peptostreptococcus magnus binding to
      kappa light chain are due to the binding of the kappa light chain at two separate
      sites on the protein L molecule. Elimination of binding site 2 through the
      mutation A66W has allowed the K(d) for kappa light chain binding at site 1 to be
      measured by stopped-flow fluorescence and isothermal titration calorimetry
      techniques, giving values of 48.0 +/- 8.0 nM and 37.5 +/- 7.3 nM respectively.
      Conversely, a double mutation Y53F/L57H eliminates binding at site 1 and has
      allowed the K(d) for binding at site 2 to be determined. Stopped-flow fluorimetry
      suggests this to be 3.4 +/- 0.8 microM in good agreement with the value of 4.6 +/
      0.8 microM determined by isothermal titration calorimetry. The mutation Y53F
      reduces the affinity of site 1 to approximately that of site 2.

PMID- 14668336
TI  - Regulation of annexin A2 by reversible glutathionylation.
AB  - The annexin A2-S100A10 heterotetramer (AIIt) is a multifunctional Ca(2+)
      dependent, phospholipid-binding, and F-actin-binding phosphoprotein composed of
      two annexin A2 subunits and two S100A10 subunits. It was reported previously that
      oxidative stress from exogenous hydrogen peroxide or generated in response to
      tumor necrosis factor-alpha results in the glutathionylation of Cys(8) of annexin
      A2. In this study, we demonstrate that AIIt is an oxidatively labile protein
      whose level of activity is regulated by the redox status of its sulfhydryl
      groups. Oxidation of AIIt by diamide resulted in a time- and concentration
      dependent loss of the ability of AIIt to interact with phospholipid liposomes and
      F-actin. The inhibitory effect of diamide on the activity of AIIt was partially
      reversed by dithiothreitol. In addition, incubation of AIIt with diamide and GSH
      resulted in the glutathionylation of AIIt in vitro. Mass spectrometry established
      the incorporation of 2 mol of GSH/mol of annexin A2 subunit at Cys(8) and
      Cys(132). Glutathionylation potentiated the inhibitory effects of diamide on the
      activity of AIIt. Furthermore, AIIt could be deglutathionylated by glutaredoxin
      (thiol transferase). Thus, we show for the first time that AIIt can undergo
      functional reactivation by glutaredoxin, therefore establishing that AIIt is
      regulated by reversible glutathionylation.

PMID- 14668337
TI  - Identification of specific functional subdomains within the linker histone H10 C
      terminal domain.
AB  - Linker histone binding to nucleosomal arrays in vitro causes linker DNA to form
      an apposed stem motif, stabilizes extensively folded secondary chromatin
      structures, and promotes self-association of individual nucleosomal arrays into
      oligomeric tertiary chromatin structures. To determine the involvement of the
      linker histone C-terminal domain (CTD) in each of these functions, and to test
      the hypothesis that the functions of this highly basic domain are mediated by
      neutralization of linker DNA negative charge, four truncation mutants were
      created that incrementally removed stretches of 24 amino acids beginning at the
      extreme C terminus of the mouse H1(0) linker histone. Native and truncated H1(0)
      proteins were assembled onto biochemically defined nucleosomal arrays and
      characterized in the absence and presence of salts to probe primary, secondary,
      and tertiary chromatin structure. Results indicate that the ability of H1(0) to
      alter linker DNA conformation and stabilize condensed chromatin structures is
      localized to specific C-terminal subdomains, rather than being equally
      distributed throughout the entire CTD. We propose that the functions of the
      linker histone CTD in chromatin are linked to the characteristic intrinsic
      disorder of this domain.

PMID- 14668338
TI  - Inhibition of apoptosis signal-regulating kinase 1 by nitric oxide through a
      thiol redox mechanism.
AB  - Nitric oxide is an endogenous thiol-reactive molecule that modulates the
      functions of many regulatory proteins by a thiol-redox mechanism. NO has now been
      shown to inhibit the activation of apoptosis signal-regulating kinase 1 (ASK1) in
      murine fibrosarcoma L929 cells through such a mechanism. Exposure of L929 cells
      to interferon-gamma resulted in the endogenous production of NO and in inhibition
      of the activation of ASK1 by hydrogen peroxide. The interferon-gamma-induced
      inhibition of ASK1 activity was blocked by N(G)-nitro-l-arginine, an inhibitor of
      NO synthase. Furthermore, the NO donor S-nitro-N-acetyl-dl-penicillamine (SNAP)
      inhibited ASK1 activity in vitro, and this inhibition was reversed by thiol
      reducing agents such as dithiothreitol and beta-mercaptoethanol. SNAP did not
      inhibit the kinase activities of MKK3, MKK6, or p38 in vitro. The inhibition of
      ASK1 by interferon-gamma was not changed by 1H- (1,2,4)oxadiazolo[4,3
      alpha]quinoxalin-1-one, an inhibitor of guanylyl cyclase nor was it mimicked by 8
      bromo-cyclic GMP. Site-directed mutagenesis revealed that replacement of cysteine
      869 of ASK1 by serine rendered this protein resistant to the inhibitory effects
      both of interferon-gamma in intact cells and of SNAP in vitro. Co
      immunoprecipitation data showed that NO production inhibited a binding of ASK1,
      but not ASK1(C869S), to MKK3 or MKK6. Moreover, interferon-gamma induced the S
      nitrosylation of endogenous ASK1 in L929 cells. Together, these results suggest
      that NO mediates the interferon-gamma-induced inhibition of ASK1 in L929 cells
      through a thiolredox mechanism.

PMID- 14668339
TI  - Androgen receptor mediates non-genomic activation of phosphatidylinositol 3-OH
      kinase in androgen-sensitive epithelial cells.
AB  - Androgens are known to modulate many cellular processes such as cell growth and
      survival by binding to the androgen receptor (AR) and activating the
      transcription of target genes. Recent data suggested that AR can also mediate non
      transcriptional actions outside the nucleus in addition to its ligand-inducible
      transcription factor function. Here, we describe a transcription-independent
      activation of the phosphatidylinositol 3-OH kinase (PI3-K) signaling pathway by
      androgens. Using non-transformed androgen-sensitive epithelial cells, we show
      that androgens enhance the PI3-K activity by promoting accumulation of
      phosphoinositide-3-P phospholipids in vitro. This activation is found in
      conjunction with an increased time-dependent phosphorylation of the downstream
      kinase AKT/protein kinase B on both Ser(473) and Thr(308) residues. Hormone
      stimulated phosphorylation of AKT requires AR since incubation with the anti
      androgen bicalutamide completely abolishes the androgen-stimulated AKT
      phosphorylation. Accordingly, we show that androgens increase AKT phosphorylation
      level in prostatic carcinoma PC3 cells only once they have been transfected with
      AR. Downstream, androgens enhance phosphorylation of transcription factor FKHR
      (Forkhead in rhabdomyosarcoma)-L1 and proapoptotic Bad protein and promote cell
      survival as they can counteract an apoptotic process. We also report that non
      genomic effects of androgens are based on direct interaction between AR and the
      p85alpha regulatory subunit of class I(A) PI3-K. Together, these novel findings
      point out an important and physiologically relevant link between androgens and
      the PI3-K/AKT signaling pathway in governing cell survival.

PMID- 14668340
TI  - Xenopus death receptor-M1 and -M2, new members of the tumor necrosis factor
      receptor superfamily, trigger apoptotic signaling by differential mechanisms.
AB  - Signaling through the tumor necrosis factor receptor (TNFR) superfamily can lead
      to apoptosis or promote cell survival, proliferation, and differentiation. A
      subset of this family, including TNFR1 and Fas, signals cell death via an
      intracellular death domain and therefore is termed the death receptor (DR)
      family. In this study, we identified new members of the DR family, designated xDR
      M1 and xDR-M2, in Xenopus laevis. The two proteins, which show high homology
      (71.7% identity), have characteristics of the DR family, that is, three cysteine
      rich domains, a transmembrane domain, and a death domain. To elucidate how
      members of xDR-M subfamily regulate cell death and survival, we examined the
      intracellular signaling mediated by these receptors in 293T and A6 cells.
      Overexpression of xDR-M2 induced apoptosis and activated caspase-8, c-Jun N
      terminal kinase, and nuclear factor-kappaB, although its death domain to a
      greater extent than did that of xDR-M1 in 293T cells. A caspase-8 inhibitor
      potently blocked this apoptosis induced by xDR-M2. In contrast, xDR-M1 showed a
      greater ability to induce apoptosis through its death domain than did xDR-M2 in
      A6 cells. Interestingly, a general serine protease inhibitor, but not the caspase
      8 inhibitor, blocked the xDR-M1-induced apoptosis. These results imply that
      activation of caspase-8 or serine protease(s) may be required for the xDR-M2- or
      xDR-M1-induced apoptosis, respectively. Although xDR-M1 and xDR-M2 are very
      similar to each other, the difference in their death domains may result in
      diverse signaling, suggesting distinct roles of xDR-M1 and xDR-M2 in cell death
      or survival.

PMID- 14668341
TI  - Ribosomes specifically bind to mammalian mitochondria via protease-sensitive
      proteins on the outer membrane.
AB  - The interaction of ribosomes with specific components of membranes is one of the
      central themes to the co-translational targeting and import of proteins. To
      examine ribosome binding to mammalian mitochondria, we used ribosome-nascent
      chain complexes (RNCs) to follow the in vitro binding of ribosomes that
      correspond to the initial targeting stage of proteins. Mitochondria were found to
      contain a limited number of RNC binding sites on the outer membrane. It required
      more than twice the amount of non-translating ribosomes to inhibit RNC binding by
      one-half, indicating that RNCs have a competitive binding advantage. In addition,
      we found that RNCs bind mainly through the ribosomal component and not the
      nascent chain. RNCs bind via protease-sensitive proteins on the outer membrane,
      as well as by protease-insensitive components suggesting that two classes of
      receptors exist. We also show that binding is sensitive to cation conditions.
      Nearly all of the binding was inhibited in 0.5 m KCl, indicating that they
      interact with the membrane primarily through electrostatic interactions. In
      addition, disruption of RNC structure by removing magnesium causes the complete
      inhibition of binding under normal binding conditions indicating that it is the
      intact ribosome that is crucial for binding and not the nascent chain. These
      findings support the hypothesis that the outer mitochondrial membrane contains
      receptors specific for ribosomes, which would support the conditions necessary
      for co-translational import.

PMID- 14668342
TI  - A highly conserved NTRK3 C-terminal sequence in the ETV6-NTRK3 oncoprotein binds
      the phosphotyrosine binding domain of insulin receptor substrate-1: an essential
      interaction for transformation.
AB  - Receptor tyrosine kinases are integral components of cellular signaling pathways
      and are frequently deregulated in malignancies. The NTRK family of neurotrophin
      receptors mediate neuronal cell survival and differentiation, but altered NTRK
      signaling has also been implicated in oncogenesis. The ETV6-NTRK3 (EN) gene
      fusion occurs in human pediatric spindle cell sarcomas and secretory breast
      carcinoma, and encodes the oligomerization domain of the ETV6 transcription
      factor fused to the protein-tyrosine kinase domain of NTRK3. The EN protein
      functions as a constitutively active protein-tyrosine kinase with potent
      transforming activity in multiple cell lineages, and EN constitutively activates
      both the Ras-MAPK and phosphatidylinositol 3-kinase-Akt pathways. EN
      transformation is associated with constitutive tyrosine phosphorylation of
      insulin receptor substrate-1 (IRS-1). Further, IRS-1 functions as the adaptor
      protein linking EN to downstream signaling pathways. However, the exact nature of
      the EN-IRS-1 interaction remains unknown. We now demonstrate that EN specifically
      binds the phosphotyrosine binding domain of IRS-1 via an interaction at the C
      terminus of EN. An EN mutant lacking the C-terminal 19 amino acids does not bind
      IRS-1 and lacks transforming ability. Moreover, expression of an IRS-1
      polypeptide containing the phosphotyrosine binding domain acts in a dominant
      negative manner to inhibit EN transformation, and overexpression of IRS-1
      potentiates EN transforming activity. These findings indicate that EN.IRS-1
      complex formation through the NTRK3 C terminus is essential for EN
      transformation.

PMID- 14668343
TI  - Differential signaling to apoptotic and necrotic cell death by Fas-associated
      death domain protein FADD.
AB  - Two general pathways for cell death have been defined, apoptosis and necrosis.
      Previous studies in Jurkat cells have demonstrated that the Fas-associated death
      domain (FADD) is required for Fas-mediated signaling to apoptosis and necrosis.
      Here we developed L929rTA cell lines that allow Tet-on inducible expression and
      FK506-binding protein (FKBP)-mediated dimerization of FADD, FADD-death effector
      domain (FADD-DED), or FADD-death domain (FADD-DD). We show that expression and
      dimerization of FADD leads to necrosis. However, pretreatment of the cells with
      the Hsp90 inhibitor geldanamycin, which leads to proteasome-mediated degradation
      of receptor interacting protein 1 (RIP1), reverts FKBP-FADD-induced necrosis to
      apoptosis. Expression and dimerization of FADD-DD mediates necrotic cell death.
      We found that FADD-DD is able to bind RIP1, another protein necessary for Fas
      mediated necrosis. Expression and dimerization of FADD-DED initiates apoptosis.
      Remarkably, in the presence of caspase inhibitors, FADD-DED mediates necrotic
      cell death. Coimmunoprecipitation studies revealed that FADD-DED in the absence
      procaspase-8 C/A is also capable of recruiting RIP1. However, when procaspase-8
      C/A and RIP1 are expressed simultaneously, FADD-DED preferentially recruits
      procaspase-8 C/A.

PMID- 14668344
TI  - Alpha-thrombin-mediated phosphatidylinositol 3-kinase activation through release
      of Gbetagamma dimers from Galphaq and Galphai2.
AB  - Chinese hamster embryonic fibroblasts (IIC9 cells) express the Galpha subunits
      Galphas, Galphai2, Galphai3, Galphao, Galpha(q/11), and Galpha13. Consistent with
      reports in other cell types, alpha-thrombin stimulates a subset of the expressed
      G proteins in IIC9 cells, namely Gi2, G13, and Gq as measured by an in vitro
      membrane [35S]guanosine 5'-O-(3-thio)triphosphate binding assay. Using specific
      Galpha peptides, which block coupling of G-protein receptors to selective G
      proteins, as well as dominant negative xanthine nucleotide-binding Galpha
      mutants, we show that activation of the phosphatidylinositol 3-kinase/Akt pathway
      is dependent on Gq and Gi2. To examine the role of the two G proteins, we
      examined the events upstream of PI 3-kinase. The activation of the PI 3
      kinase/Akt pathway by alpha-thrombin in IIC9 cells is blocked by the expression
      of dominant negative Ras and beta-arrestin1 (Phillips-Mason, P. J., Raben, D. M.,
      and Baldassare, J. J. (2000) J. Biol. Chem. 275, 18046-18053, and Goel, R.,
      Phillips-Mason, P. J., Raben, D. M., and Baldassare, J. J. (2002) J. Biol. Chem.
      277, 18640-18648), indicating a role for Ras and beta-arrestin1. Interestingly,
      inhibition of Gi2 and Gq activation blocks Ras activation and beta-arrestin1
      membrane translocation, respectively. Furthermore, expression of the Gbetagamma
      sequestrant, alpha-transducin, inhibits both Ras activation and membrane
      translocation of beta-arrestin1, suggesting that Gbetagamma dimers from Galphai2
      and Galphaq activate different effectors to coordinately regulate the PI 3
      kinase/Akt pathway.

PMID- 14668345
TI  - Hypertriglyceridemia in lecithin-cholesterol acyltransferase-deficient mice is
      associated with hepatic overproduction of triglycerides, increased lipogenesis,
      and improved glucose tolerance.
AB  - Lecithin-cholesterol acyltransferase deficiency is frequently associated with
      hypertriglyceridemia (HTG) in animal models and humans. We investigated the
      mechanism of HTG in the ldlr-/- x lcat-/- (double knockout (dko)) mice using the
      ldlr-/- x lcat+/+ (knock-out (ko)) littermates as control. Mean fasting
      triglyceride (TG) levels in the dko mice were elevated 1.75-fold compared with
      their controls (p < 0.002). Both the very low density lipoprotein and the low
      density lipoprotein/intermediate density lipoprotein fractions separated by fast
      protein liquid chromatography were TG-enriched in the dko mice. In vitro
      lipolysis assay revealed that the dko mouse very low density lipoprotein (d <
      1.019 g/ml) fraction separated by ultracentrifugation was a more efficient
      substrate for lipolysis by exogenous bovine lipoprotein lipase. Post-heparin
      lipoprotein lipase activity was reduced by 61% in the dko mice. Hepatic TG
      production rate, determined after intravenous Triton WR1339 injection, was
      increased 8-fold in the dko mice. Hepatic mRNA levels of sterol regulatory
      element binding protein-1 (srebp-1) and its target genes acetyl-CoA carboxylase-1
      (acc-1), fatty acid synthase (fas), and stearoyl-CoA desaturase-1 (scd-1) were
      significantly elevated in the dko mice compared with the ko control. The hepatic
      mRNA levels of LXRalpha (lxralpha) and its target genes including angiopoietin
      like protein 3 (angptl-3) in the dko mice were unchanged. Fasting glucose and
      insulin levels were reduced by 31 and 42%, respectively in the dko mice, in
      conjunction with a 49% reduction in hepatic pepck-1 mRNA (p = 0.014). Both the
      HTG and the improved fasting glucose phenotype seen in the dko mice are at least
      in part attributable to an up-regulation of the hepatic srebp-1c gene.

PMID- 14668346
TI  - Kaposi's sarcoma-associated herpesvirus-encoded vIRF-3 stimulates the
      transcriptional activity of cellular IRF-3 and IRF-7.
AB  - Kaposi's sarcoma-associated herpesvirus has been linked to Kaposi's sarcoma, body
      cavity-based lymphoma, and Castleman's disease. The Kaposi's sarcoma-associated
      herpesvirus genome contains a cluster of open reading frames encoding proteins
      (vIRFs) with homology to the cellular transcription factors of the interferon
      regulatory factor family. vIRF-3, also called LANA2, is a latently expressed
      nuclear protein. Here we demonstrate that vIRF-3 directly interacts with cellular
      interferon regulatory factor (IRF) IRF-3, IRF-7, and the transcriptional co
      activator CBP/p300. The mapping of the vIRF-3 binding domain revealed that vIRF-3
      associates with both IRF-3 and IRF-7 through its C-terminal region. The p300
      domain, which interacts with vIRF-3, is distinct from the previously identified
      IBiD domain, to which both vIRF-1 and IRF-3 bind. Thus, in contrast to vIRF-1,
      vIRF-3 neither blocks the interaction between IRF-3 and p300 nor inhibits the
      histone acetylation. Although vIRF-3 is not a DNA-binding protein, it is
      recruited to the IFNA promoters via its interaction with IRF-3 and IRF-7. The
      presence of vIRF-3 in the enhanceosome assembled on the IFNA promoters increases
      binding of IRF-3, IRF-7, and acetylated histone H3 to this promoter region.
      Consequently, vIRF-3 stimulates the IRF-3- and IRF-7-mediated activation of type
      I interferon (IFNA and IFNB) genes and the synthesis of biologically active type
      I interferons in infected B cells. These studies illustrate that vIRF-3 and vIRF
      1 have clearly distinct functions. In addition to its co-repressor activity, vIRF
      3 can also act as a transcriptional activator on genes controlled by cellular IRF
      3 and IRF-7.

PMID- 14668347
TI  - Functional characterization of Caenorhabditis elegans heteromeric amino acid
      transporters.
AB  - Mammalian heteromeric amino acid transporters (HATs) are composed of a multi
      transmembrane spanning catalytic protein covalently associated with a type II
      glycoprotein (e.g. 4F2hc, rBAT) through a disulfide bond. Caenorhabditis elegans
      has nine genes encoding close homologues of the HAT catalytic proteins. Three of
      these genes (designated AAT-1 to AAT-3) have a much higher degree of similarity
      to the mammalian homologues than the other six, including the presence of a
      cysteine residue at the position known to form a disulfide bridge to the
      glycoprotein partner in mammalian HATs. C. elegans also has two genes encoding
      homologues of the heteromeric amino acid transporter type II glycoprotein
      subunits (designated ATG-1 and ATG-2). Both ATG, and/or AAT-1, -2, -3 proteins
      were expressed in Xenopus oocytes and tested for amino acid transport function.
      This screen revealed that AAT-1 and AAT-3 facilitate amino acid transport when
      expressed together with ATG-2 but not with ATG-1 or the mammalian type II
      glycoproteins 4F2hc and rBAT. AAT-1 and AAT-3 covalently bind to both C. elegans
      ATG glycoproteins, but only the pairs with ATG-2 traffic to the oocyte surface.
      Both of these functional, surface-expressed C. elegans HATs transport most
      neutral amino acids and display the highest transport rate for l-Ala and l-Ser
      (apparent K(m) 100 microm range). Similar to their mammalian counterparts, the C.
      elegans HATs function as (near) obligatory amino acid exchangers. Taken together,
      this study demonstrates that the heteromeric structure and the amino acid
      exchange function of HATs have been conserved throughout the evolution of
      nematodes to mammals.

PMID- 14668348
TI  - 11-Dehydro-thromboxane B2, a stable thromboxane metabolite, is a full agonist of
      chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) in
      human eosinophils and basophils.
AB  - Thromboxane (TX) A(2), a cyclooxygenase-derived mediator involved in allergic
      responses, is rapidly converted in vivo to a stable metabolite, 11-dehydro
      TXB(2), which is considered to be biologically inactive. In this study, we found
      that 11-dehydro-TXB(2), but not the TXA(2) analogue U46,619 or TXB(2), activated
      eosinophils and basophils, as assayed by flow cytometric shape change. 11-Dehydro
      TXB(2) was also chemotactic for eosinophils but did not induce, nor inhibit,
      platelet aggregation. Chemoattractant receptor-homologous molecule expressed on
      TH2 cells (CRTH2) is an important chemoattractant receptor expressed by
      eosinophils, basophils, and TH2 lymphocytes, and prostaglandin (PG)D(2) has been
      shown to be its principal ligand. 11-Dehydro-TXB(2) induced calcium flux mainly
      from intracellular stores in eosinophils, and this response was desensitized
      after stimulation with PGD(2) but not other eosinophil chemoattractants. Shape
      change responses of eosinophils and basophils to 11-dehydro-TXB(2) were inhibited
      by the thromboxane (TP)/CRTH2 receptor antagonist ramatroban, but not the
      selective TP antagonist SQ29,548, and were insensitive to pertussis toxin. The
      phospholipase C inhibitor U73,122 attenuated both 11-dehydro-TXB(2)- and PGD(2)
      induced shape change. 11-Dehydro-TXB(2) also induced the chemotaxis of BaF/3
      cells transfected with hCRTH2 but not naive BaF/3 cells. At a threshold
      concentration, 11-dehydro-TXB(2) had no antagonistic effect on CRTH2-mediated
      responses as induced by PGD2. These data show that 11-dehydro-TXB(2) is a full
      agonist of the CRTH2 receptor and hence might cause CRTH2 activation in cellular
      contexts where PGD-synthase is not present. Given its production in the allergic
      lung, antagonism of the 11-dehydro-TXB(2)/CRTH2axis may be of therapeutic
      relevance.

PMID- 14668349
TI  - The Plasmodium falciparum PfGatp is an endoplasmic reticulum membrane protein
      important for the initial step of malarial glycerolipid synthesis.
AB  - During its 48-h asexual life cycle within human erythrocytes, Plasmodium
      falciparum grows to many times its own size and divides to produce 16-32 new
      parasites. This rapid multiplication requires active synthesis of new membranes
      and is fueled by phospholipid precursors and fatty acids that are scavenged from
      the human host. Plasmodium membrane biogenesis relies heavily on the expression
      of parasite enzymes that incorporate these precursors into phospholipids.
      However, little is known about the genes involved in membrane biogenesis or where
      this process takes place within the parasite. Here, we describe the analysis in
      P. falciparum of the first step of phospholipid biosynthesis that controls
      acylation of glycerol 3-phosphate (GPAT) at the sn-1 position. We show that this
      activity is of parasite origin and is specific for glycerol 3-phosphate
      substrate. We have identified the gene, PfGAT, encoding this activity in P.
      falciparum and reconstituted its codon composition for optimal expression in the
      yeast Saccharomyces cerevisiae. PfGAT complements the lethality of a yeast double
      mutant gat1Deltagat2Delta, lacking GPAT activity. Biochemical analysis revealed
      that PfGatp is a low affinity GPAT enzyme with a high specificity for C16:0 and
      C16:1 substrates. PfGatp is an integral membrane protein of the endoplasmic
      reticulum expressed throughout the intraerythrocytic life cycle of the parasite
      but induced mainly at the trophozoite stage. This study, which describes the
      first protozoan GPAT gene, reveals an important role for the endoplasmic
      reticulum in the initial step of Plasmodium membrane biogenesis.

PMID- 14668350
TI  - Structural requirements of synthetic muropeptides to synergize with
      lipopolysaccharide in cytokine induction.
AB  - Muropeptides contribute to the recognition of bacteria by modulating immune
      responses: the structural requirements for adjuvant activity were described in
      the seventies. During the last years, our knowledge of bacterial pattern
      recognition has increased dramatically and the importance of the absence of
      contaminations in both muropeptide preparations and other bacterial stimuli has
      become clear. We investigated a panel of 15 synthetic Limulus-negative
      muropeptides, four of them synthesized for the first time, as to their potency to
      synergize with lipopolysaccharide (LPS) in cytokine induction in human whole
      blood. No muropeptide was capable of stimulating cytokine release from human
      blood. However, as little as 20 nM of the muropeptides N-acetyl-muramyl-l-alanyl
      d-isoglutamine (muramyl dipeptide, M(AdiQ)), N-acetyl-glucosamine-muramyl
      dipeptide GM(AdiQ), or C(18)M(AdiQ), which carries a non-natural additional fatty
      acid, sufficed to induce an up to 3 log-order shift in tumor necrosis factor
      alpha-release in response to 100 pg/ml LPS. The release of interleukin-1beta,
      interleukin-6, and interleukin-10 was also significantly enhanced although to a
      lesser extent. The synergistic effect was stereoselective with M(AdiQ) being the
      minimal active principle. Synergy was also observed on the transcriptional level
      by means of real-time PCR. Smaller molecules like N-acetylmuramic acid (M), aM,
      carrying a naturally occurring 1,6-anhydro-bound in M or M(A), containing only
      the amino acid l-alanine neither synergized with LPS nor influenced the synergy
      of other muropeptides with LPS. In conclusion, these data show that nanomolar
      quantities of muropeptides dramatically potentiate LPS-induced monocyte
      activation. This has implications for pyrogenicity testing and endotoxemia in
      patients.

PMID- 14668351
TI  - Autocatalytic conversion of recombinant prion proteins displays a species
      barrier.
AB  - The most unorthodox feature of the prion disease is the existence of an abnormal
      infectious isoform of the prion protein, PrP(Sc). According to the "protein-only"
      hypothesis, PrP(Sc) propagates its abnormal conformation in an autocatalytic
      manner using the normal isoform, PrP(C), as a substrate. Because autocatalytic
      conversion is considered a key element of prion replication, in this study I
      tested whether in vitro conversion of recombinant PrP into abnormal isoform
      displays specific features of an autocatalytic process. I found that recombinant
      human PrP formed two distinct beta-sheet rich isoforms, the beta-oligomer and the
      amyloid fibrils. The kinetics of the fibrils formation measured at different pH
      values were consistent with a model in which the beta-oligomer was not on the
      kinetic pathway to the fibrillar form. As judged by electron microscopy, an
      acidic pH favored to the long fibrils, whereas short fibrils morphologically
      similar to "prion rods" were formed at neutral pH. At neutral pH the conversion
      to the fibrils can be seeded with small aliquots of preformed fibrils. As small
      as 0.001% aliquot displayed seeding activity. The conversion of human PrP was
      seeded with high efficacy only with the preformed fibrils of human but not mouse
      PrP and vice versa. These studies illustrate that in vitro conversion of
      recombinant PrP displays specific features of an autocatalytic process and mimics
      the transmission barrier of prion propagation observed in vivo. I speculate that
      this model can be used as a rapid assay for assessing the intrinsic propensities
      of prion transmission between different species.

PMID- 14668352
TI  - The SANT2 domain of the murine tumor cell DnaJ-like protein 1 human homologue
      interacts with alpha1-antichymotrypsin and kinetically interferes with its serpin
      inhibitory activity.
AB  - The murine tumor cell DnaJ-like protein 1 or MTJ1/ERdj1 is a membrane J-domain
      protein enriched in microsomal and nuclear fractions. We previously showed that
      its lumenal J-domain stimulates the ATPase activity of the molecular chaperone
      BiP/GRP78 (Chevalier, M., Rhee, H., Elguindi, E. C., and Blond, S. Y. (2000) J.
      Biol. Chem. 275, 19620-19627). MTJ1/ERdj1 also contains a large carboxyl-terminal
      cytosolic extension composed of two tryptophan-mediated repeats or SANT domains
      for which the function(s) is unknown. Here we describe the cloning of the human
      homologue HTJ1 and its interaction with alpha(1)-antichymotrypsin (ACT), a member
      of the serine proteinase inhibitor (serpin) family. The interaction was initially
      identified in a two-hybrid screening and further confirmed in vitro by dot blots,
      native electrophoresis, and fluorescence studies. The second SANT domain of HTJ1
      (SANT2) was found to be sufficient for binding to ACT, both in yeast and in
      vitro. Single tryptophan-alanine substitutions at two strictly conserved residues
      significantly (Trp-497) or totally (Trp-520) abolished the interaction with ACT.
      SANT2 binds to human ACT with an intrinsic affinity equal to 0.5 nm.
      Preincubation of ACT with nearly stoichiometric concentrations of SANT2 wild-type
      but not SANT2: W520A results in an apparent loss of ACT inhibitory activity
      toward chymotrypsin. Kinetic analysis indicates that the formation of the
      covalent inhibitory complex ACT-chymotrypsin is significantly delayed in the
      presence of SANT2 with no change on the catalytic efficiency of the enzyme. This
      work demonstrates for the first time that the SANT2 domain of MTJ1/HTJ1/ERdj1
      mediates stable and high affinity protein-protein interactions.

PMID- 14668353
TI  - Lipopenia and skin barrier abnormalities in DGAT2-deficient mice.
AB  - The synthesis of triglycerides is catalyzed by two known acyl-CoA:diacylglycerol
      acyltransferase (DGAT) enzymes. Although they catalyze the same biochemical
      reaction, these enzymes share no sequence homology, and their relative functions
      are poorly understood. Gene knockout studies in mice have revealed that DGAT1
      contributes to triglyceride synthesis in tissues and plays an important role in
      regulating energy metabolism but is not essential for life. Here we show that
      DGAT2 plays a fundamental role in mammalian triglyceride synthesis and is
      required for survival. DGAT2-deficient (Dgat2(-/-)) mice are lipopenic and die
      soon after birth, apparently from profound reductions in substrates for energy
      metabolism and from impaired permeability barrier function in the skin. DGAT1 was
      unable to compensate for the absence of DGAT2, supporting the hypothesis that the
      two enzymes play fundamentally different roles in mammalian triglyceride
      metabolism.

PMID- 14668354
TI  - Robert C. King: an appreciation of his work.

PMID- 14668355
TI  - Teaching advanced genetics without lectures.
AB  - In an effort to increase student engagement and therefore student learning, an
      advanced genetics course was developed in which traditional lectures were
      eliminated. Instead, students were required to complete reading assignments
      before each class meeting, and those readings were then the topic of group
      discussion. Assigned readings alternated between text assignments and articles
      from the primary literature. Students were made accountable for their own
      preparation by the administration of a quiz at the start of each class. Group
      discussion of the topics engaged students in the learning process and
      readministration of the quiz at the end of class allowed them to benefit from the
      group interaction and understanding. Interspersing text readings and primary
      literature led to student understanding of how genetic knowledge is acquired and
      interpreted and how experimental detail leads to the construction of general
      models.

PMID- 14668356
TI  - Genomic rearrangements at rrn operons in Salmonella.
AB  - Most Salmonella serovars are general pathogens that infect a variety of hosts.
      These "generalist" serovars cause disease in many animals from reptiles to
      mammals. In contrast, a few serovars cause disease only in a specific host. Host
      specific serovars can cause a systemic, often fatal disease in one species yet
      remain avirulent in other species. Host-specific Salmonella frequently have large
      genomic rearrangements due to recombination at the ribosomal RNA (rrn) operons
      while the generalists consistently have a conserved chromosomal arrangement. To
      determine whether this is the result of an intrinsic difference in recombination
      frequency or a consequence of lifestyle difference between generalist and host
      specific Salmonella, we determined the frequency of rearrangements in vitro.
      Using lacZ genes as portable regions of homology for inversion analysis, we found
      that both generalist and host-specific serovars of Salmonella have similar
      tolerances to chromosomal rearrangements in vitro. Using PCR and genetic
      selection, we found that generalist and host-specific serovars also undergo
      rearrangements at rrn operons at similar frequencies in vitro. These observations
      indicate that the observed difference in genomic stability between generalist and
      host-specific serovars is a consequence of their distinct lifestyles, not
      intrinsic differences in recombination frequencies.

PMID- 14668358
TI  - Evolution in Saccharomyces cerevisiae: identification of mutations increasing
      fitness in laboratory populations.
AB  - Since the publication of the complete sequence of the genome of Saccharomyces
      cerevisiae, a number of comprehensive investigations have been initiated to gain
      insight into cellular function. The focus of these studies has been to identify
      genes essential for survival in specific environments or those that when mutated
      cause gross phenotypic defects in growth. Here we describe Ty1-based mutational
      approaches designed to identify genes, which when mutated generate evolutionarily
      significant phenotypes causing small but positive increments on fitness. As
      expected, Ty1 mutations with a positive fitness effect were in the minority.
      However, mutations in two loci, one inactivating FAR3 and one upstream of CYR1,
      identified in evolving populations, were shown to have small but significantly
      positive fitness effects.

PMID- 14668357
TI  - Activity of mitochondrially synthesized reporter proteins is lower than that of
      imported proteins and is increased by lowering cAMP in glucose-grown
      Saccharomyces cerevisiae cells.
AB  - We selected for increased phenotypic expression of a synthetic cox2::arg8m-G66S
      reporter gene inserted into Saccharomyces cerevisiae mtDNA in place of COX2.
      Recessive mutations in ras2 and cyr1, as well as elevated dosage of PDE2, allowed
      cox2::arg8m-G66S to support Arg prototrophy. Each of these genetic alterations
      should decrease cellular cAMP levels. The resulting signal was transduced through
      redundant action of the three cAMP-dependent protein kinases, TPK1, TPK2, and
      TPK3. ras2 had little or no effect on the level of wild-type Arg8p encoded by
      cox2::ARG8m, but did increase Arg8p activity, as judged by growth phenotype. ras2
      also caused increased fluorescence in cells carrying the synthetic cox3::GFPm
      reporter in mtDNA, but had little effect on the steady-state level of GFP
      polypeptide detected immunologically. Thus, decreased cAMP levels did not affect
      the synthesis of mitochondrially coded protein reporters in glucose-grown cells,
      but rather elevated activities in the matrix that promote efficient folding.
      Furthermore, we show that when Arg8p is synthesized in the cytoplasm and imported
      into mitochondria, it has greater activity than when it is synthesized in the
      matrix. Thus, mitochondrially synthesized proteins may not have the same access
      to matrix chaperones as cytoplasmically synthesized proteins emerging from the
      import apparatus.

PMID- 14668359
TI  - A role for GEA1 and GEA2 in the organization of the actin cytoskeleton in
      Saccharomyces cerevisiae.
AB  - Profilin is an actin monomer-binding protein implicated in the polymerization of
      actin filaments. In the budding yeast Saccharomyces cerevisiae, the pfy1-111
      rho2delta double mutant has severe growth and actin cytoskeletal defects. The
      GEA1 and GEA2 genes, which code for paralog guanosine exchange factors for Arf
      proteins, were identified as multicopy suppressors of the mutant phenotype. These
      two genes restored the polarized distribution of actin cortical patches and
      produced visible actin cables in both the pfy1-111 rho2delta and pfy1delta cells.
      Thus, overexpression of GEA1 or GEA2 bypassed the requirement for profilin in
      actin cable formation. In addition, gea1 gea2 double mutants showed defects in
      budding and in actin cytoskeleton organization, while overexpression of GEA1 or
      GEA2 led to the formation of supernumerary actin cable-like structures in a
      Bni1p/Bnr1p-dependent manner. The ADP-ribosylation factor Arf3p may be a target
      of Gea1p/Gea2p, since overexpression of ARF3 partially suppressed the profilin
      deficient phenotype and a deletion of ARF3 exacerbated the phenotype of a pfy1
      111 mutant. Gea1p, Gea2p, Arf1p, and Arf2p but not Arf3p are known to function in
      vesicular transport between the endoplasmic reticulum and the Golgi. In this
      work, we demonstrate a role for Gea1p, Gea2p, and Arf3p in the organization of
      the actin cytoskeleton.

PMID- 14668361
TI  - The global transcriptional activator of Saccharomyces cerevisiae, Gcr1p, mediates
      the response to glucose by stimulating protein synthesis and CLN-dependent cell
      cycle progression.
AB  - Growth of Saccharomyces cerevisiae requires coordination of cell cycle events
      (e.g., new cell wall deposition) with constitutive functions like energy
      generation and duplication of protein mass. The latter processes are stimulated
      by the phosphoprotein Gcr1p, a transcriptional activator that operates through
      two different Rap1p-mediated mechanisms to boost expression of glycolytic and
      ribosomal protein genes, respectively. Simultaneous disruption of both mechanisms
      results in a loss of glucose responsiveness and a dramatic drop in translation
      rate. Since a critical rate of protein synthesis (CRPS) is known to mediate
      passage through Start and determine cell size by modulating levels of Cln3p, we
      hypothesized that GCR1 regulates cell cycle progression by coordinating it with
      growth. We therefore constructed and analyzed gcr1delta cln3delta and gcr1delta
      cln1delta cln2delta strains. Both strains are temperature and cold sensitive;
      interestingly, they exhibit different arrest phenotypes. The gcr1delta cln3delta
      strain becomes predominantly unbudded with 1N DNA content (G1 arrest), whereas
      gcr1delta cln1delta cln2delta cells exhibit severe elongation and apparent M
      phase arrest. Further analysis demonstrated that the Rap1p/Gcr1p complex mediates
      rapid growth in glucose by stimulating both cellular metabolism and CLN
      transcription.

PMID- 14668360
TI  - Phenotypic and transcriptional plasticity directed by a yeast mitogen-activated
      protein kinase network.
AB  - The yeast pheromone/filamentous growth MAPK pathway mediates both mating and
      invasive-growth responses. The interface between this MAPK module and the
      transcriptional machinery consists of a network of two MAPKs, Fus3 and Kss1; two
      regulators, Rst1 and Rst2 (a.k.a. Dig1 and Dig2); and two transcription factors,
      Ste12 and Tec1. Of 16 possible combinations of gene deletions in FUS3, KSS1,
      RST1, and RST2 in the sigma1278 background, 10 display constitutive invasive
      growth. Rst1 was the primary negative regulator of invasive growth, while other
      components either attenuated or enhanced invasive growth, depending on the
      genetic context. Despite activation of the invasive response by lesions at the
      same level in the MAPK pathway, transcriptional profiles of different invasive
      mutant combinations did not exhibit a unified program of gene expression. The
      distal MAPK regulatory network is thus capable of generating phenotypically
      similar invasive-growth states (an attractor) from different molecular
      architectures (trajectories) that can functionally compensate for one another.
      This systems-level robustness may also account for the observed diversity of
      signals that trigger invasive growth.

PMID- 14668362
TI  - Five RecA-like proteins of Schizosaccharomyces pombe are involved in meiotic
      recombination.
AB  - The genome of Schizosaccharomyces pombe contains five genes that code for
      proteins with sequence similarity to the Escherichia coli recombination protein
      RecA: rad51+, rhp55+, rhp57+, rlp1+, and dmc1+. We analyzed the effect of
      deletion of each of these genes on meiotic recombination and viability of spores.
      Meiotic recombination levels were different from wild type in all recA-related
      mutants in several genetic intervals, suggesting that all five RecA homologs of
      S. pombe are required for normal levels of meiotic recombination. Spore viability
      was reduced in rad51, rhp55, and rhp57 mutants, but not in rlp1 and dmc1. It is
      argued that reduction of crossover is not the only cause for the observed
      reduction of spore viability. Analysis of double and triple mutants revealed that
      Rad51 and Dmc1 play major and partially overlapping roles in meiotic
      recombination, while Rhp55, Rhp57, and Rlp1 play accessory roles. Remarkably,
      deletion of Rlp1 decreases the frequency of intergenic recombination
      (crossovers), but increases intragenic recombination (gene conversion). On the
      basis of our results, we present a model for the involvement of five RecA-like
      proteins of S. pombe in meiotic recombination and discuss their respective roles.

PMID- 14668363
TI  - Cellular differentiation in response to nutrient availability: The repressor of
      meiosis, Rme1p, positively regulates invasive growth in Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, the transition from a nutrient-rich to a
      nutrient-limited growth medium typically leads to the implementation of a
      cellular adaptation program that results in invasive growth and/or the formation
      of pseudohyphae. Complete depletion of essential nutrients, on the other hand,
      leads either to entry into a nonbudding, metabolically quiescent state referred
      to as G0 in haploid strains or to meiosis and sporulation in diploids. Entry into
      meiosis is repressed by the transcriptional regulator Rme1p, a zinc-finger
      containing DNA-binding protein. In this article, we show that Rme1p positively
      regulates invasive growth and starch metabolism in both haploid and diploid
      strains by directly modifying the transcription of the FLO11 (also known as MUC1)
      and STA2 genes, which encode a cell wall-associated protein essential for
      invasive growth and a starch-degrading glucoamylase, respectively. Genetic
      evidence suggests that Rme1p functions independently of identified signaling
      modules that regulate invasive growth and of other transcription factors that
      regulate FLO11 and that the activation of FLO11 is dependent on the presence of a
      promoter sequence that shows significant homology to identified Rme1p response
      elements (RREs). The data suggest that Rme1p functions as a central switch
      between different cellular differentiation pathways.

PMID- 14668364
TI  - The Ras/PKA signaling pathway may control RNA polymerase II elongation via the
      Spt4p/Spt5p complex in Saccharomyces cerevisiae.
AB  - The Ras signaling pathway in Saccharomyces cerevisiae controls cell growth via
      the cAMP-dependent protein kinase, PKA. Recent work has indicated that these
      effects on growth are due, in part, to the regulation of activities associated
      with the C-terminal domain (CTD) of the largest subunit of RNA polymerase II.
      However, the precise target of these Ras effects has remained unknown. This study
      suggests that Ras/PKA activity regulates the elongation step of the RNA
      polymerase II transcription process. Several lines of evidence indicate that
      Spt5p in the Spt4p/Spt5p elongation factor is the likely target of this control.
      First, the growth of spt4 and spt5 mutants was found to be very sensitive to
      changes in Ras/PKA signaling activity. Second, mutants with elevated levels of
      Ras activity shared a number of specific phenotypes with spt5 mutants and vice
      versa. Finally, Spt5p was efficiently phosphorylated by PKA in vitro. Altogether,
      the data suggest that the Ras/PKA pathway might be directly targeting a component
      of the elongating polymerase complex and that this regulation is important for
      the normal control of yeast cell growth. These data point out the interesting
      possibility that signal transduction pathways might directly influence the
      elongation step of RNA polymerase II transcription.

PMID- 14668365
TI  - The SONB(NUP98) nucleoporin interacts with the NIMA kinase in Aspergillus
      nidulans.
AB  - The Aspergillus nidulans NIMA kinase is essential for mitotic entry. At
      restrictive temperature, temperature-sensitive nimA alleles arrest in G2, before
      accumulation of NIMA in the nucleus. We performed a screen for extragenic
      suppressors of the nimA1 allele and isolated two cold-sensitive son (suppressor
      of nimA1) mutants. The sonA1 mutant encoded a nucleoporin that is a homolog of
      yeast Gle2/Rae1. We have now cloned SONB, a second nucleoporin genetically
      interacting with NIMA. sonB is essential and encodes a homolog of the human
      NUP98/NUP96 precursor. Similar to NUP98/NUP96, SONB(NUP98/NUP96) is
      autoproteolytically cleaved to generate SONB(NUP98) and SONB(NUP96). SONB(NUP98)
      localizes to the nuclear pore complex and contains a GLEBS domain (Gle2 binding
      sequence) that binds SONA(GLE2). A point mutation within the GLEBS domain of
      SONB1(NUP98) suppresses the temperature sensitivity of the nimA1 allele and
      compromises the physical interaction between SONA(GLE2) and SONB1(NUP98). The
      sonB1 mutation also causes sensitivity to hydroxyurea. We isolated the histone
      H2A-H2B gene pair as a copy-number suppressor of sonB1 cold sensitivity and
      hydroxyurea sensitivity. The data suggest that the nucleoporins SONA(GLE2) and
      SONB(NUP98) and the NIMA kinase interact and regulate nuclear accumulation of
      mitotic regulators to help promote mitosis.

PMID- 14668366
TI  - Suppressor mutations bypass the requirement of fluG for asexual sporulation and
      sterigmatocystin production in Aspergillus nidulans.
AB  - Asexual sporulation (conidiation) in the filamentous fungus Aspergillus nidulans
      requires the early developmental activator fluG. Loss of fluG results in the
      blockage of both conidiation and production of the mycotoxin sterigmatocystin
      (ST). To investigate molecular mechanisms of fluG-dependent developmental
      activation, 40 suppressors of fluG (SFGs) that conidiate without fluG have been
      isolated and characterized. Genetic analyses showed that an individual
      suppression is caused by a single second-site mutation, and that all sfg
      mutations but one are recessive. Pairwise meiotic crosses grouped mutations to
      four loci, 31 of them to sfgA, 6 of them to sfgB, and 1 each to sfgC and sfgD,
      respectively. The only dominant mutation, sfgA38, also mapped to the sfgA locus,
      suggesting a dominant negative mutation. Thirteen sfgA and 1 sfgC mutants
      elaborated conidiophores in liquid submerged culture, indicating that loss of
      either of these gene functions not only bypasses fluG function but also results
      in hyperactive conidiation. While sfg mutants show varying levels of restored
      conidiation, all recovered the ability to produce ST at near wild-type levels.
      The fact that at least four loci are defined by recessive sfg mutations indicates
      that multiple genes negatively regulate conidiation downstream of fluG and that
      the activity of fluG is required to remove such repressive effects.

PMID- 14668367
TI  - Pka, Ras and RGS protein interactions regulate activity of AflR, a Zn(II)2Cys6
      transcription factor in Aspergillus nidulans.
AB  - Sterigmatocystin (ST) is a carcinogenic polyketide produced by several
      filamentous fungi including Aspergillus nidulans. Expression of ST biosynthetic
      genes (stc genes) requires activity of a Zn(II)2Cys6 transcription factor, AflR.
      aflR is transcriptionally and post-transcriptionally regulated by a G
      protein/cAMP/protein kinase A (PkaA) signaling pathway involving FlbA, an RGS
      (regulator of G-protein signaling) protein. Prior genetic data showed that FlbA
      transcriptional regulation of aflR was PkaA dependent. Here we show that mutation
      of three PkaA phosphorylation sites in AflR allows resumption of stc expression
      in an overexpression pkaA background but does not remediate stc expression in a
      deltaflbA background. This demonstrates negative regulation of AflR activity by
      phosphorylation and shows that FlbA post-transcriptional regulation of aflR is
      PkaA independent. AflR nucleocytoplasmic location further supports PkaA
      independent regulation of AflR by FlbA. GFP-tagged AflR is localized to the
      cytoplasm when pkaA is overexpressed but nuclearly located in a deltaflbA
      background. aflR is also transcriptionally and post-transcriptionally regulated
      by RasA. RasA transcriptional control of aflR is PkaA independent but RasA post
      transcriptional control of AflR is partially mediated by PkaA.

PMID- 14668368
TI  - The PHOA and PHOB cyclin-dependent kinases perform an essential function in
      Aspergillus nidulans.
AB  - Unlike Pho85 of Saccharomyces cerevisiae, the highly related PHOA cyclin
      dependent kinase (CDK) of Aspergillus nidulans plays no role in regulation of
      enzymes involved in phosphorous acquisition but instead modulates differentiation
      in response to environmental conditions, including limited phosphorous. Like
      PHO85, Aspergillus phoA is a nonessential gene. However, we find that expression
      of dominant-negative PHOA inhibits growth, suggesting it may have an essential
      but redundant function. Supporting this we have identified another cyclin
      dependent kinase, PHOB, which is 77% identical to PHOA. Deletion of phoB causes
      no phenotype, even under phosphorous-limited growth conditions. To investigate
      the function of phoA/phoB, double mutants were selected from a cross of strains
      containing null alleles and by generating a temperature-sensitive allele of phoA
      in a deltaphoB background. Double-deleted ascospores were able to germinate but
      had a limited capacity for nuclear division, suggesting a cell cycle defect.
      Longer germination revealed morphological defects. The temperature-sensitive phoA
      allele caused both nuclear division and polarity defects at restrictive
      temperature, which could be complemented by expression of mammalian CDK5.
      Therefore, an essential function exists in A. nidulans for the Pho85-like kinase
      pair PHOA and PHOB, which may involve cell cycle control and morphogenesis.

PMID- 14668369
TI  - Quantitative classification and natural clustering of Caenorhabditis elegans
      behavioral phenotypes.
AB  - Genetic analysis of nervous system function relies on the rigorous description of
      behavioral phenotypes. However, standard methods for classifying the behavioral
      patterns of mutant Caenorhabditis elegans rely on human observation and are
      therefore subjective and imprecise. Here we describe the application of machine
      learning to quantitatively define and classify the behavioral patterns of C.
      elegans nervous system mutants. We have used an automated tracking and image
      processing system to obtain measurements of a wide range of morphological and
      behavioral features from recordings of representative mutant types. Using
      principal component analysis, we represented the behavioral patterns of eight
      mutant types as data clouds distributed in multidimensional feature space.
      Cluster analysis using the k-means algorithm made it possible to quantitatively
      assess the relative similarities between different behavioral phenotypes and to
      identify natural phenotypic clusters among the data. Since the patterns of
      phenotypic similarity identified in this study closely paralleled the functional
      similarities of the mutant gene products, the complex phenotypic signatures
      obtained from these image data appeared to represent an effective diagnostic of
      the mutants' underlying molecular defects.

PMID- 14668370
TI  - Patterns of selection against transposons inferred from the distribution of Tc1,
      Tc3 and Tc5 insertions in the mut-7 line of the nematode Caenorhabditis elegans.
AB  - To identify the factors (selective or mutational) that affect the distribution of
      transposable elements (TEs) within a genome, it is necessary to compare the
      pattern of newly arising element insertions to the pattern of element insertions
      that have been fixed in a population. To do this, we analyzed the distribution of
      recent mutant insertions of the Tc1, Tc3, and Tc5 elements in a mut-7 background
      of the nematode Caenorhabditis elegans and compared it to the distribution of
      element insertions (presumably fixed) within the sequenced genome. Tc1 elements
      preferentially insert in regions with high recombination rates, whereas Tc3 and
      Tc5 do not. Although Tc1 and Tc3 both insert in TA dinucleotides, there is no
      clear relationship between the frequency of insertions and the TA dinucleotide
      density. There is a strong selection against TE insertions within coding regions:
      the probability that a TE will be fixed is at least 31 times lower in coding
      regions than in noncoding regions. Contrary to the prediction of theoretical
      models, we found that the selective pressure against TE insertions does not
      increase with the recombination rate. These findings indicate that the
      distribution of these three transposon families in the genome of C. elegans is
      determined essentially by just two factors: the pattern of insertions, which is a
      characteristic of each family, and the selection against insertions within coding
      regions.

PMID- 14668371
TI  - A microsatellite variability screen for positive selection associated with the
      "out of Africa" habitat expansion of Drosophila melanogaster.
AB  - We report a "hitchhiking mapping" study in D. melanogaster, which searches for
      genomic regions with reduced variability. The study's aim was to identify
      selective sweeps associated with the "out of Africa" habitat expansion. We
      scanned 103 microsatellites on chromosome 3 and 102 microsatellites on the X
      chromosome for reduced variability in non-African populations. When the
      chromosomes were analyzed separately, the number of loci with a significant
      reduction in variability only slightly exceeded the expectation under neutrality-
      six loci on the third chromosome and four loci on the X chromosome. However, non
      African populations also have a more pronounced average loss in variability on
      the X chromosomes as compared to the third chromosome, which suggests the action
      of selection. Therefore, comparing the X chromosome to the autosome yields a
      higher number of significantly reduced loci. However, a more pronounced loss of
      variability on the X chromosome may be caused by demographic events rather than
      by natural selection. We therefore explored a range of demographic scenarios and
      found that some of these captured most, but not all aspects of our data. More
      theoretical work is needed to evaluate how demographic events might
      differentially affect X chromosomes and autosomes and to estimate the most likely
      scenario associated with the out of Africa expansion of D. melanogaster.

PMID- 14668373
TI  - Study of dosage compensation in Drosophila.
AB  - Using a sensitive RT-QPCR assay, we analyzed the regulatory effects of sex and
      different dosage compensation mutations in Drosophila. To validate the assay, we
      showed that regulation for several genes indeed varied with the number of
      functional copies of that gene. We then confirmed that dosage compensation
      occurred for most genes we examined in male and female flies. Finally, we
      examined the effects on regulation of several genes in the MSL pathway, presumed
      to be involved in sex-dependent determination of regulation. Rather than seeing
      global alterations of either X chromosomal or autosomal genes, regulation of
      genes on either the X chromosome or the autosomes could be elevated, depressed,
      or unaltered between sexes in unpredictable ways for the various MSL mutations.
      Relative dosage for a given gene between the sexes could vary at different
      developmental times. Autosomal genes often showed deranged regulatory levels,
      indicating they were in pathways perturbed by X chromosomal changes. As
      exemplified by the BR-C locus and its dependent Sgs genes, multiple genes in a
      given pathway could exhibit coordinate regulatory modulation. The variegated
      pattern shown for expression of both X chromosomal and autosomal loci underscores
      the complexity of gene expression so that the phenotype of MSL mutations does not
      reflect only simple perturbations of genes on the X chromosome.

PMID- 14668372
TI  - A sensitized genetic screen to identify novel regulators and components of the
      Drosophila janus kinase/signal transducer and activator of transcription pathway.
AB  - The JAK/STAT pathway exerts pleiotropic effects on a wide range of developmental
      processes in Drosophila. Four key components have been identified: Unpaired, a
      secreted ligand; Domeless, a cytokine-like receptor; Hopscotch, a JAK kinase; and
      Stat92E, a STAT transcription factor. The identification of additional components
      and regulators of this pathway remains an important issue. To this end, we have
      generated a transgenic line where we misexpress the upd ligand in the developing
      Drosophila eye. GMR-upd transgenic animals have dramatically enlarged eye
      imaginal discs and compound eyes that are normally patterned. We demonstrate that
      the enlarged-eye phenotype is a result of an increase in cell number, and not
      cell volume, and arises from additional mitoses in larval eye discs. Thus, the
      GMR-upd line represents a system in which the proliferation and differentiation
      of eye precursor cells are separable. Removal of one copy of stat92E
      substantially reduces the enlarged-eye phenotype. We performed an F1 deficiency
      screen to identify dominant modifiers of the GMR-upd phenotype. We have
      identified 9 regions that enhance this eye phenotype and two specific enhancers:
      C-terminal binding protein and Daughters against dpp. We also identified 20
      regions that suppress GMR-upd and 13 specific suppressors: zeste-white 13,
      pineapple eye, Dichaete, histone 2A variant, headcase, plexus, kohtalo, crumbs,
      hedgehog, decapentaplegic, thickveins, saxophone, and Mothers against dpp.

PMID- 14668374
TI  - Heterochromatic self-association, a determinant of nuclear organization, does not
      require sequence homology in Drosophila.
AB  - Chromosomes of higher eukaryotes contain blocks of heterochromatin that can
      associate with each other in the interphase nucleus. A well-studied example of
      heterochromatic interaction is the brown(Dominant) (bwD) chromosome of D.
      melanogaster, which contains an approximately 1.6-Mbp insertion of AAGAG repeats
      near the distal tip of chromosome 2. This insertion causes association of the tip
      with the centric heterochromatin of chromosome 2 (2h), which contains megabases
      of AAGAG repeats. Here we describe an example, other than bwD, in which distally
      translocated heterochromatin associates with centric heterochromatin.
      Additionally, we show that when a translocation places bwD on a different
      chromosome, bwD tends to associate with the centric heterochromatin of this
      chromosome, even when the chromosome contains a small fraction of the sequence
      homology present elsewhere. To further test the importance of sequence homology
      in these interactions, we used interspecific mating to introgress the bwD allele
      from D. melanogaster into D. simulans, which lacks the AAGAG on the autosomes. We
      find that D. simulans bwD associates with 2h, which lacks the AAGAG sequence,
      while it does not associate with the AAGAG containing X chromosome
      heterochromatin. Our results show that intranuclear association of separate
      heterochromatic blocks does not require that they contain the same sequence.

PMID- 14668375
TI  - Recombination, dominance and selection on amino acid polymorphism in the
      Drosophila genome: contrasting patterns on the X and fourth chromosomes.
AB  - Surveys of nucleotide polymorphism and divergence indicate that the average
      selection coefficient on Drosophila proteins is weakly positive. Similar surveys
      in mitochondrial genomes and in the selfing plant Arabidopsis show that weak
      negative selection has operated. These differences have been attributed to the
      low recombination environment of mtDNA and Arabidopsis that has hindered adaptive
      evolution through the interference effects of linkage. We test this hypothesis
      with new sequence surveys of proteins lying in low recombination regions of the
      Drosophila genome. We surveyed >3800 bp across four proteins at the tip of the X
      chromosome and >3600 bp across four proteins on the fourth chromosome in 24
      strains of D. melanogaster and 5 strains of D. simulans. This design seeks to
      study the interaction of selection and linkage by comparing silent and
      replacement variation in semihaploid (X chromosome) and diploid (fourth
      chromosome) environments lying in regions of low recombination. While the data do
      indicate very low rates of exchange, all four gametic phases were observed both
      at the tip of the X and across the fourth chromosome. Silent variation is very
      low at the tip of the X (thetaS = 0.0015) and on the fourth chromosome (thetaS =
      0.0002), but the tip of the X shows a greater proportional loss of variation than
      the fourth shows relative to normal-recombination regions. In contrast,
      replacement polymorphism at the tip of the X is not reduced (thetaR = 0.00065,
      very close to the X chromosome average). MK and HKA tests both indicate a
      significant excess of amino acid polymorphism at the tip of the X relative to the
      fourth. Selection is significantly negative at the tip of the X (Nes = -1.53) and
      nonsignificantly positive on the fourth (Nes approximately 2.9), analogous to the
      difference between mtDNA (or Arabidopsis) and the Drosophila genome average. Our
      distal X data are distinct from regions of normal recombination where the X shows
      a deficiency of amino acid polymorphism relative to the autosomes, suggesting
      more efficient selection against recessive deleterious replacement mutations. We
      suggest that the excess amino acid polymorphism on the distal X relative to the
      fourth chromosome is due to (1) differences in the mutation rate for selected
      mutations on the distal X or (2) a greater relaxation of selection from stronger
      linkage-related interference effects on the distal X. This relaxation of
      selection is presumed to be greater in magnitude than the difference in
      efficiency of selection between X-linked vs. autosomal selection.

PMID- 14668376
TI  - Effect of the Suppressor of Underreplication (SuUR) gene on position-effect
      variegation silencing in Drosophila melanogaster.
AB  - It has been previously shown that the SuUR gene encodes a protein located in
      intercalary and pericentromeric heterochromatin in Drosophila melanogaster
      polytene chromosomes. The SuUR mutation suppresses the formation of ectopic
      contacts and DNA underreplication in polytene chromosomes; SuUR+ in extra doses
      enhances the expression of these characters. This study demonstrates that
      heterochromatin-dependent PEV silencing is also influenced by SuUR. The SuUR
      protein localizes to chromosome regions compacted as a result of PEV; the SuUR
      mutation suppresses DNA underreplication arising in regions of polytene
      chromosomes undergoing PEV. The SuUR mutation also suppresses variegation of both
      adult morphological characters and chromatin compaction observed in rearranged
      chromosomes. In contrast, SuUR+ in extra doses and its overexpression enhance
      variegation. Thus, SuUR affects PEV silencing in a dose-dependent manner.
      However, its effect is expressed weaker than that of the strong modifier Su(var)2
      5.

PMID- 14668377
TI  - Protein evolution and codon usage bias on the neo-sex chromosomes of Drosophila
      miranda.
AB  - The neo-sex chromosomes of Drosophila miranda constitute an ideal system to study
      the effects of recombination on patterns of genome evolution. Due to a fusion of
      an autosome with the Y chromosome, one homolog is transmitted clonally. Here, I
      compare patterns of molecular evolution of 18 protein-coding genes located on the
      recombining neo-X and their homologs on the nonrecombining neo-Y chromosome. The
      rate of protein evolution has significantly increased on the neo-Y lineage since
      its formation. Amino acid substitutions are accumulating uniformly among neo-Y
      linked genes, as expected if all loci on the neo-Y chromosome suffer from a
      reduced effectiveness of natural selection. In contrast, there is significant
      heterogeneity in the rate of protein evolution among neo-X-linked genes, with
      most loci being under strong purifying selection and two genes showing evidence
      for adaptive evolution. This observation agrees with theory predicting that
      linkage limits adaptive protein evolution. Both the neo-X and the neo-Y
      chromosome show an excess of unpreferred codon substitutions over preferred ones
      and no difference in this pattern was observed between the chromosomes. This
      suggests that there has been little or no selection maintaining codon bias in the
      D. miranda lineage. A change in mutational bias toward AT substitutions also
      contributes to the decline in codon bias. The contrast in patterns of molecular
      evolution between amino acid mutations and synonymous mutations on the neo-sex
      linked genes can be understood in terms of chromosome-specific differences in
      effective population size and the distribution of selective effects of mutations.

PMID- 14668378
TI  - Genetic modifiers of tauopathy in Drosophila.
AB  - In Alzheimer's disease and related disorders, the microtubule-associated protein
      Tau is abnormally hyperphosphorylated and aggregated into neurofibrillary
      tangles. Mutations in the tau gene cause familial frontotemporal dementia. To
      investigate the molecular mechanisms responsible for Tau-induced
      neurodegeneration, we conducted a genetic modifier screen in a Drosophila model
      of tauopathy. Kinases and phosphatases comprised the major class of modifiers
      recovered, and several candidate Tau kinases were similarly shown to enhance Tau
      toxicity in vivo. Despite some clinical and pathological similarities among
      neurodegenerative disorders, a direct comparison of modifiers between different
      Drosophila disease models revealed that the genetic pathways controlling Tau and
      polyglutamine toxicity are largely distinct. Our results demonstrate that kinases
      and phosphatases control Tau-induced neurodegeneration and have important
      implications for the development of therapies in Alzheimer's disease and related
      disorders.

PMID- 14668379
TI  - A temperature-sensitive allele of Drosophila sesB reveals acute functions for the
      mitochondrial adenine nucleotide translocase in synaptic transmission and dynamin
      regulation.
AB  - Rapidly reversible, temperature-sensitive (ts) paralytic mutants of Drosophila
      have been useful in delineating immediate in vivo functions of molecules involved
      in synaptic transmission. Here we report isolation and characterization of orangi
      (org), an enhancer of shibire (shi), a ts paralytic mutant in Drosophila dynamin.
      org is an allele of the stress sensitive B (sesB) locus that encodes a
      mitochondrial adenine nucleotide translocase (ANT) and results in a unique ts
      paralytic behavior that is accompanied by a complete loss of synaptic
      transmission in the visual system. sesB(org) reduces the restrictive temperature
      for all shi(ts) alleles tested except for shi(ts1). This characteristic allele
      specific interaction of sesB(org) with shi is shared by abnormal wing discs
      (awd), a gene encoding nucleoside diphosphate kinase (NDK). sesB(org) shows
      independent synergistic interactions, an observation that is consistent with a
      shared pathway by which org and awd influence shi function. Genetic and
      electrophysiological analyses presented here, together with the observation that
      the sesB(org) mutation reduces biochemically assayed ANT activity, suggest a
      model in which a continuous mitochondrial ANT-dependent supply of ATP is required
      to sustain NDK-dependent activation of presynaptic dynamin during a normal range
      of synaptic activity.

PMID- 14668380
TI  - Drosophila calmodulin mutants with specific defects in the musculature or in the
      nervous system.
AB  - We have studied lethal mutations in the single calmodulin gene (Cam) of
      Drosophila to gain insight into the in vivo functions of this important calcium
      sensor. As a result of maternal calmodulin (CaM) in the mature egg, lethality is
      delayed until the postembryonic stages. Prior to death in the first larval
      instar, Cam nulls show a striking behavioral abnormality (spontaneous backward
      movement) whereas a mutation, Cam7, that results in a single amino acid change
      (V91G) produces a very different phenotype: short indented pupal cases and pupal
      death with head eversion defects. We show here that the null behavioral phenotype
      originates in the nervous system and involves a CaM function that requires
      calcium binding to all four sites of the protein. Further, backward movement can
      be induced in hypomorphic mutants by exposure to high light levels. In contrast,
      the V91G mutation specifically affects the musculature and causes abnormal
      calcium release in response to depolarization of the muscles. Genetic interaction
      studies suggest that failed regulation of the muscle calcium release channel, the
      ryanodine receptor, is the major defect underlying the Cam7 phenotype.

PMID- 14668381
TI  - Demography and natural selection have shaped genetic variation in Drosophila
      melanogaster: a multi-locus approach.
AB  - Demography and selection have been recognized for their important roles in
      shaping patterns of nucleotide variability. To investigate the relative effects
      of these forces in the genome of Drosophila melanogaster, we used a multi-locus
      scan (105 fragments) of X-linked DNA sequence variation in a putatively ancestral
      African and a derived European population. Surprisingly, we found evidence for a
      recent size expansion in the African population, i.e., a significant excess of
      singletons at a chromosome-wide level. In the European population, such an excess
      was not detected. In contrast to the African population, we found evidence for
      positive natural selection in the European sample: (i) a large number of loci
      with low levels of variation and (ii) a significant excess of derived variants at
      the low-variation loci that are fixed in the European sample but rare in the
      African population. These results are consistent with the hypothesis that the
      European population has experienced frequent selective sweeps in the recent past
      during its adaptation to new habitats. Our study shows the advantages of a
      genomic approach (over a locus-specific analysis) in disentangling demographic
      and selective forces.

PMID- 14668382
TI  - Patterns of nucleotide polymorphism and divergence in the odorant-binding protein
      genes OS-E and OS-F: analysis in the melanogaster species subgroup of Drosophila.
AB  - The Olfactory Specific-E and -F genes (OS-E and OS-F) belong to the odorant
      binding protein gene family, which includes the general odorant-binding proteins
      and the pheromone-binding proteins. In Drosophila melanogaster, these genes are
      arranged in tandem in a genomic region near the centromere of chromosome arm 3R.
      We examined the pattern of DNA sequence variation in an approximately 7-kb
      genomic region encompassing the two OS genes in four species of the melanogaster
      subgroup of Drosophila and in a population sample of D. melanogaster. We found
      that both the OS-E and the OS-F gene are present in all surveyed species.
      Nucleotide divergence estimates would support that the two genes are functional,
      although they diverge in their functional constraint. The pattern of nucleotide
      variation in D. melanogaster also differed between genes. Variation in the OS-E
      gene region exhibited an unusual and distinctive pattern: (i) a relatively high
      number of fixed amino acid replacements in the encoded protein and (ii) a peak of
      nucleotide polymorphism around the OS-E gene. These results are unlikely under
      the neutral model and suggest the action of natural selection in the evolution of
      the two odorant-binding protein genes.

PMID- 14668383
TI  - Linkage disequilibrium patterns across a recombination gradient in African
      Drosophila melanogaster.
AB  - Previous multilocus surveys of nucleotide polymorphism have documented a genome
      wide excess of intralocus linkage disequilibrium (LD) in Drosophila melanogaster
      and D. simulans relative to expectations based on estimated mutation and
      recombination rates and observed levels of diversity. These studies examined
      patterns of variation from predominantly non-African populations that are thought
      to have recently expanded their ranges from central Africa. Here, we analyze
      polymorphism data from a Zimbabwean population of D. melanogaster, which is
      likely to be closer to the standard population model assumptions of a large
      population with constant size. Unlike previous studies, we find that levels of LD
      are roughly compatible with expectations based on estimated rates of crossing
      over. Further, a detailed examination of genes in different recombination
      environments suggests that markers near the telomere of the X chromosome show
      considerably less linkage disequilibrium than predicted by rates of crossing
      over, suggesting appreciable levels of exchange due to gene conversion. Assuming
      that these populations are near mutation-drift equilibrium, our results are most
      consistent with a model that posits heterogeneity in levels of exchange due to
      gene conversion across the X chromosome, with gene conversion being a minor
      determinant of LD levels in regions of high crossing over. Alternatively, if
      levels of exchange due to gene conversion are not negligible in regions of high
      crossing over, our results suggest a marked departure from mutation-drift
      equilibrium (i.e., toward an excess of LD) in this Zimbabwean population. Our
      results also have implications for the dynamics of weakly selected mutations in
      regions of reduced crossing over.

PMID- 14668384
TI  - Quantitative trait loci for susceptibility to tapeworm infection in the red flour
      beetle.
AB  - Parasites have profound effects on host ecology and evolution, and the effects of
      parasites on host ecology are often influenced by the magnitude of host
      susceptibility to parasites. Many parasites have complex life cycles that require
      intermediate hosts for their transmission, but little is known about the genetic
      basis of the intermediate host's susceptibility to these parasites. This study
      examined the genetic basis of susceptibility to a tapeworm (Hymenolepis diminuta)
      in the red flour beetle (Tribolium castaneum) that serves as an intermediate host
      in its transmission. Quantitative trait loci (QTL) mapping experiments were
      conducted with two independent segregating populations using amplified fragment
      length polymorphism (AFLP) markers and randomly amplified polymorphic DNA (RAPD)
      markers. A total of five QTL that significantly affected beetle susceptibility
      were identified in the two reciprocal crosses. Two common QTL on linkage groups 3
      and 6 were identified in both crosses with similar effects on the phenotype, and
      three QTL were unique to each cross. In one cross, the three main QTL accounted
      for 29% of the total phenotypic variance and digenic epistasis explained 39% of
      the variance. In the second cross, the four main QTL explained 62% of the
      variance and digenic epistasis accounted for only 5% of the variance. The actions
      of these QTL were either overdominance or underdominance. Our results suggest
      that the polygenic nature of beetle susceptibility to the parasites and epistasis
      are important genetic mechanisms for the maintenance of variation within or among
      beetle strains in susceptibility to tapeworm infection.

PMID- 14668385
TI  - Sequence differentiation associated with an inversion on the neo-X chromosome of
      Drosophila americana.
AB  - Sex chromosomes originate from pairs of autosomes that acquire controlling genes
      in the sex-determining cascade. Universal mechanisms apparently influence the
      evolution of sex chromosomes, because this chromosomal pair is characteristically
      heteromorphic in a broad range of organisms. To examine the pattern of initial
      differentiation between sex chromosomes, sequence analyses were performed on a
      pair of newly formed sex chromosomes in Drosophila americana. This species has
      neo-sex chromosomes as a result of a centromeric fusion between the X chromosome
      and an autosome. Sequences were analyzed from the Alcohol dehydrogenase (Adh),
      big brain (bib), and timeless (tim) gene regions, which represent separate
      positions along this pair of neo-sex chromosomes. In the northwestern range of
      the species, the bib and Adh regions exhibit significant sequence differentiation
      for neo-X chromosomes relative to neo-Y chromosomes from the same geographic
      region and other chromosomal populations of D. americana. Furthermore, a
      nucleotide site defining a common haplotype in bib is shown to be associated with
      a paracentric inversion [In(4)ab] on the neo-X chromosome, and this inversion
      suppresses recombination between neo-X and neo-Y chromosomes. These observations
      are consistent with the inversion acting as a recombination modifier that
      suppresses exchange between these neo-sex chromosomes, as predicted by models of
      sex chromosome evolution.

PMID- 14668386
TI  - Targeted gene expression using the GAL4/UAS system in the silkworm Bombyx mori.
AB  - The silkworm Bombyx mori is one of the most well-studied insects in terms of both
      genetics and physiology and is recognized as the model lepidopteran insect. To
      develop an efficient system for analyzing gene function in the silkworm, we
      investigated the feasibility of using the GAL4/UAS system in conjunction with
      piggyBac vector-mediated germ-line transformation for targeted gene expression.
      To drive the GAL4 gene, we used two endogenous promoters that originated from the
      B. mori actin A3 (BmA3) and fibroin light-chain (FiL) genes and the artificial
      promoter 3xP3. GFP was used as the reporter. In initial tests of the function of
      the GAL4/UAS system, we generated transgenic animals that carried the UAS-GFP
      construct plus either BmA3-GAL4 or 3xP3-GAL4. GFP fluorescence was observed in
      the tissues of GFP-positive animals, in which both promoters drove GAL4 gene
      expression. Animals that possessed only the GAL4 gene or UAS-GFP construct did
      not show GFP fluorescence. In addition, as a further test of the ability of the
      GAL4/UAS system to drive tissue-specific expression we constructed FiL-GAL4 lines
      with 3xP3-CFP as the transformation marker. FiL-GAL4 x UAS-GFP crosses showed GFP
      expression in the posterior silk gland, in which the endogenous FiL gene is
      normally expressed. These results show that the GAL4/UAS system is applicable to
      B. mori and emphasize the potential of this system for controlled analyses of B.
      mori gene function.

PMID- 14668387
TI  - Genetic and phenotypic analysis of alleles of the Drosophila chromosomal JIL-1
      kinase reveals a functional requirement at multiple developmental stages.
AB  - In this study we provide a cytological and genetic characterization of the JIL-1
      locus in Drosophila. JIL-1 is an essential chromosomal tandem kinase and in JIL-1
      null animals chromatin structure is severely perturbed. Using a range of JIL-1
      hypomorphic mutations, we show that they form an allelic series. JIL-1 has a
      strong maternal effect and JIL-1 activity is required at all stages of
      development, including embryonic, larval, and pupal stages. Furthermore, we
      identified a new allele of JIL-1, JIL-1(h9), that encodes a truncated protein
      missing COOH-terminal sequences. Remarkably, the truncated JIL-1 protein can
      partially restore viability without rescuing the defects in polytene chromosome
      organization. This suggests that sequences within this region of JIL-1 play an
      important role in establishing and/or maintaining normal chromatin structure. By
      analyzing the effects of JIL-1 mutations we provide evidence that JIL-1 function
      is necessary for the normal progression of several developmental processes at
      different developmental stages such as oogenesis and segment specification. We
      propose that JIL-1 may exert such effects by a general regulation of chromatin
      structure affecting gene expression.

PMID- 14668389
TI  - Population subdivision and molecular sequence variation: theory and analysis of
      Drosophila ananassae data.
AB  - Population subdivision complicates analysis of molecular variation. Even if
      neutrality is assumed, three evolutionary forces need to be considered:
      migration, mutation, and drift. Simplification can be achieved by assuming that
      the process of migration among and drift within subpopulations is occurring fast
      compared to mutation and drift in the entire population. This allows a two-step
      approach in the analysis: (i) analysis of population subdivision and (ii)
      analysis of molecular variation in the migrant pool. We model population
      subdivision using an infinite island model, where we allow the migration/drift
      parameter Theta to vary among populations. Thus, central and peripheral
      populations can be differentiated. For inference of Theta, we use a coalescence
      approach, implemented via a Markov chain Monte Carlo (MCMC) integration method
      that allows estimation of allele frequencies in the migrant pool. The second step
      of this approach (analysis of molecular variation in the migrant pool) uses the
      estimated allele frequencies in the migrant pool for the study of molecular
      variation. We apply this method to a Drosophila ananassae sequence data set. We
      find little indication of isolation by distance, but large differences in the
      migration parameter among populations. The population as a whole seems to be
      expanding. A population from Bogor (Java, Indonesia) shows the highest variation
      and seems closest to the species center.

PMID- 14668388
TI  - A theoretical model for the regulation of Sex-lethal, a gene that controls sex
      determination and dosage compensation in Drosophila melanogaster.
AB  - Cell fate commitment relies upon making a choice between different developmental
      pathways and subsequently remembering that choice. Experimental studies have
      thoroughly investigated this central theme in biology for sex determination. In
      the somatic cells of Drosophila melanogaster, Sex-lethal (Sxl) is the master
      regulatory gene that specifies sexual identity. We have developed a theoretical
      model for the initial sex-specific regulation of Sxl expression. The model is
      based on the well-documented molecular details of the system and uses a
      stochastic formulation of transcription. Numerical simulations allow quantitative
      assessment of the role of different regulatory mechanisms in achieving a robust
      switch. We establish on a formal basis that the autoregulatory loop involved in
      the alternative splicing of Sxl primary transcripts generates an all-or-none
      bistable behavior and constitutes an efficient stabilization and memorization
      device. The model indicates that production of a small amount of early Sxl
      proteins leaves the autoregulatory loop in its off state. Numerical simulations
      of mutant genotypes enable us to reproduce and explain the phenotypic effects of
      perturbations induced in the dosage of genes whose products participate in the
      early Sxl promoter activation.

PMID- 14668390
TI  - Genetic modifier screens in Drosophila demonstrate a role for Rho1 signaling in
      ecdysone-triggered imaginal disc morphogenesis.
AB  - Drosophila adult leg development provides an ideal model system for
      characterizing the molecular mechanisms of hormone-triggered morphogenesis. A
      pulse of the steroid hormone ecdysone at the onset of metamorphosis triggers the
      rapid transformation of a flat leg imaginal disc into an immature adult leg,
      largely through coordinated changes in cell shape. In an effort to identify links
      between the ecdysone signal and the cytoskeletal changes required for leg
      morphogenesis, we performed two large-scale genetic screens for dominant
      enhancers of the malformed leg phenotype associated with a mutation in the
      ecdysone-inducible broad early gene (br1). From a screen of >750 independent
      deficiency and candidate mutation stocks, we identified 17 loci on the autosomes
      that interact strongly with br1. In a complementary screen of approximately
      112,000 F1 progeny of EMS-treated br1 animals, we recovered 26 mutations that
      enhance the br1 leg phenotype [E(br) mutations]. Rho1, stubbloid, blistered
      (DSRF), and cytoplasmic Tropomyosin were identified from these screens as br1
      interacting genes. Our findings suggest that ecdysone exerts its effects on leg
      morphogenesis through a Rho1 signaling cascade, a proposal that is supported by
      genetic interaction studies between the E(br) mutations and mutations in the Rho1
      signaling pathway. In addition, several E(br) mutations produce unexpected
      defects in midembryonic morphogenetic movements. Coupled with recent evidence
      implicating ecdysone signaling in these embryonic morphogenetic events, our
      results suggest that a common ecdysone-dependent, Rho1-mediated regulatory
      pathway controls morphogenesis during the two major transitions in the life
      cycle, embryogenesis and metamorphosis.

PMID- 14668391
TI  - Genetic interactions between the RhoA and Stubble-stubbloid loci suggest a role
      for a type II transmembrane serine protease in intracellular signaling during
      Drosophila imaginal disc morphogenesis.
AB  - The Drosophila RhoA (Rho1) GTPase is essential for postembryonic morphogenesis of
      leg and wing imaginal discs. Mutations in RhoA enhance leg and wing defects
      associated with mutations in zipper, the gene encoding the heavy chain of
      nonmuscle myosin II. We demonstrate here that mutations affecting the RhoA
      signaling pathway also interact genetically with mutations in the Stubble
      stubbloid (Sb-sbd) locus that encodes an unusual type II transmembrane serine
      protease required for normal leg and wing morphogenesis. In addition, a leg
      malformation phenotype associated with overexpression of Sb-sbd in prepupal leg
      discs is suppressed when RhoA gene dose is reduced, suggesting that RhoA and Sb
      sbd act in a common pathway during leg morphogenesis. We also characterized six
      mutations identified as enhancers of zipper mutant leg defects. Three of these
      genes encode known members of the RhoA signaling pathway (RhoA, DRhoGEF2, and
      zipper). The remaining three enhancer of zipper mutations interact genetically
      with both RhoA and Sb-sbd mutations, suggesting that they encode additional
      components of the RhoA signaling pathway in imaginal discs. Our results provide
      evidence that the type II transmembrane serine proteases, a class of proteins
      linked to human developmental abnormalities and pathology, may be associated with
      intracellular signaling required for normal development.

PMID- 14668392
TI  - Green fluorescent protein tagging Drosophila proteins at their native genomic
      loci with small P elements.
AB  - We describe a technique to tag Drosophila proteins with GFP at their native
      genomic loci. This technique uses a new, small P transposable element (the Wee-P)
      that is composed primarily of the green fluorescent protein (GFP) sequence
      flanked by consensus splice acceptor and splice donor sequences. We demonstrate
      that insertion of the Wee-P can generate GFP fusions with native proteins. We
      further demonstrate that GFP-tagged proteins have correct subcellular
      localization and can be expressed at near-normal levels. We have used the Wee-P
      to tag genes with a wide variety of functions, including transmembrane proteins.
      A genetic analysis of 12 representative fusion lines demonstrates that loss-of
      function phenotypes are not caused by the Wee-P insertion. This technology allows
      the generation of GFP-tagged reagents on a genome-wide scale with diverse
      potential applications.

PMID- 14668393
TI  - Distribution of temperature tolerance quantitative trait loci in Arctic charr
      (Salvelinus alpinus) and inferred homologies in rainbow trout (Oncorhynchus
      mykiss).
AB  - We searched for quantitative trait loci (QTL) affecting upper temperature
      tolerance (UTT) in crosses between the Nauyuk Lake and Fraser River strains of
      Arctic charr (Salvelinus alpinus) using survival analysis. Two QTL were detected
      by using two microsatellite markers after correcting for experiment-wide error. A
      comparative mapping approach localized these two QTL to homologous linkage groups
      containing UTT QTL in rainbow trout (Oncorhynchus mykiss). Additional marginal
      associations were detected in several families in regions homologous to those
      with QTL in rainbow trout. Thus, the genes underlying UTT QTL may antedate the
      divergence of these two species, which occurred by approximately 16 MYA. The data
      also indicate that one pair of homeologs (ancestrally duplicated chromosomal
      segments) have contained QTL in Arctic charr since the evolution of salmonids
      from a tetraploid ancestor 25-100 MYA. This study represents one of the first
      examples of comparative QTL mapping in an animal polyploid group and illustrates
      the fate of QTL after genome duplication and reorganization.

PMID- 14668394
TI  - Abundant mtDNA diversity and ancestral admixture in Colombian criollo cattle (Bos
      taurus).
AB  - Various cattle populations in the Americas (known as criollo breeds) have an
      origin in some of the first livestock introduced to the continent early in the
      colonial period (16th and 17th centuries). These cattle constitute a potentially
      important genetic reserve as they are well adapted to local environments and show
      considerable variation in phenotype. To examine the genetic ancestry and
      diversity of Colombian criollo we obtained mitochondrial DNA control region
      sequence information for 110 individuals from seven breeds. Old World haplogroup
      T3 is the most commonly observed CR lineage in criollo (0.65), in agreement with
      a mostly European ancestry for these cattle. However, criollo also shows
      considerable frequencies of haplogroups T2 (0.9) and T1 (0.26), with T1 lineages
      in criollo being more diverse than those reported for West Africa. The
      distribution and diversity of Old World lineages suggest some North African
      ancestry for criollo, probably as a result of the Arab occupation of Iberia prior
      to the European migration to the New World. The mtDNA diversity of criollo is
      higher than that reported for European and African cattle and is consistent with
      a differentiated ancestry for some criollo breeds.

PMID- 14668395
TI  - The contribution of genetic diversity to the spread of infectious diseases in
      livestock populations.
AB  - This article uses stochastic simulations with a compartmental epidemic model to
      quantify the impact of genetic diversity within animal populations on the
      transmission of infectious disease. Genetic diversity is defined by the number of
      distinct genotypes in the population conferring resistance to microparasitic
      (e.g., viral or bacterial) infections. Scenarios include homogeneous populations
      and populations composed of few (finite-locus model) or many (infinitesimal
      model) genotypes. Genetic heterogeneity has no impact upon the expected value of
      the basic reproductive ratio (the primary description of the transmission of
      infection) but affects the variability of this parameter. Consequently,
      increasing genetic heterogeneity is associated with an increased probability of
      minor epidemics and decreased probabilities of both major (catastrophic)
      epidemics and no epidemics. Additionally, heterogeneity per se is associated with
      a breakdown in the expected relationship between the basic reproductive ratio and
      epidemic severity, which has been developed for homogeneous populations, with
      increasing heterogeneity generally resulting in fewer infected animals than
      expected. Furthermore, increased heterogeneity is associated with decreased
      disease-dependent mortality in major epidemics and a complex trend toward
      decreased duration of these epidemics. In summary, more heterogeneous populations
      are not expected to suffer fewer epidemics on average, but are less likely to
      suffer catastrophic epidemics.

PMID- 14668396
TI  - An analysis of microsatellite loci in Arabidopsis thaliana: mutational dynamics
      and application.
AB  - Microsatellite loci are among the most commonly used molecular markers. These
      loci typically exhibit variation for allele frequency distribution within a
      species. However, the factors contributing to this variation are not well
      understood. To expand on the current knowledge of microsatellite evolution, 20
      microsatellite loci were examined for 126 accessions of the flowering plant,
      Arabidopsis thaliana. Substantial variability in mutation pattern among loci was
      found, most of which cannot be explained by the assumptions of the traditional
      stepwise mutation model or infinite alleles model. Here it is shown that the
      degree of locus diversity is strongly correlated with the number of contiguous
      repeats, more so than with the total number of repeats. These findings support a
      strong role for repeat disruptions in stabilizing microsatellite loci by reducing
      the substrate for polymerase slippage and recombination. Results of cluster
      analyses are also presented, demonstrating the potential of microsatellite loci
      for resolving relationships among accessions of A. thaliana.

PMID- 14668397
TI  - Mapping of quantitative trait loci controlling adaptive traits in coastal Douglas
      fir. III. Quantitative trait loci-by-environment interactions.
AB  - Quantitative trait loci (QTL) were mapped in the woody perennial Douglas fir
      (Pseudotsuga menziesii var. menziesii [Mirb.] Franco) for complex traits
      controlling the timing of growth initiation and growth cessation. QTL were
      estimated under controlled environmental conditions to identify QTL interactions
      with photoperiod, moisture stress, winter chilling, and spring temperatures. A
      three-generation mapping population of 460 cloned progeny was used for genetic
      mapping and phenotypic evaluations. An all-marker interval mapping method was
      used for scanning the genome for the presence of QTL and single-factor ANOVA was
      used for estimating QTL-by-environment interactions. A modest number of QTL were
      detected per trait, with individual QTL explaining up to 9.5% of the phenotypic
      variation. Two QTL-by-treatment interactions were found for growth initiation,
      whereas several QTL-by-treatment interactions were detected among growth
      cessation traits. This is the first report of QTL interactions with specific
      environmental signals in forest trees and will assist in the identification of
      candidate genes controlling these important adaptive traits in perennial plants.

PMID- 14668398
TI  - The extended auricle1 (eta1) gene is essential for the genetic network
      controlling postinitiation maize leaf development.
AB  - The maize leaf is composed of distinct regions with clear morphological
      boundaries. The ligule and auricle mark the boundary between distal blade and
      proximal sheath and are amenable to genetic study due to the array of mutants
      that affect their formation without severely affecting viability. Herein, we
      describe the novel maize gene extended auricle1 (eta1), which is essential for
      proper formation of the blade/sheath boundary. Homozygous eta1 individuals have a
      wavy overgrowth of auricle tissue and the blade/sheath boundary is diffuse.
      Double-mutant combinations of eta1 with genes in the knox and liguleless pathways
      result in synergistic and, in some cases, dosage-dependent interactions. While
      the phenotype of eta1 mutant individuals resembles that of dominant knox
      overexpression phenotypes, eta1 mutant leaves do not ectopically express knox
      genes. In addition, eta1 interacts synergistically with lg1 and lg2, but does not
      directly affect the transcription of either gene in leaf primordia. We present
      evidence based on genetic and molecular analyses that eta1 provides a downstream
      link between the knox and liguleless pathways.

PMID- 14668399
TI  - Heterochronic expression of sexual reproductive programs during apomictic
      development in Tripsacum.
AB  - Some angiosperms reproduce by apomixis, a natural way of cloning through seeds.
      Apomictic plants bypass both meiosis and egg cell fertilization, producing
      progeny that are genetic replicas of the mother plant. In this report, we analyze
      reproductive development in Tripsacum dactyloides, an apomictic relative of
      maize, and in experimental apomictic hybrids between maize and Tripsacum. We show
      that apomictic reproduction is characterized by an alteration of developmental
      timing of both sporogenesis and early embryo development. The absence of female
      meiosis in apomictic Tripsacum results from an early termination of female
      meiosis. Similarly, parthenogenetic development of a maternal embryo in apomicts
      results from precocious induction of early embryogenesis events. We also show
      that male meiosis in apomicts is characterized by comparable asynchronous
      expression of developmental stages. Apomixis thus results in an array of possible
      phenotypes, including wild-type sexual development. Overall, our observations
      suggest that apomixis in Tripsacum is a heterochronic phenotype; i.e., it relies
      on a deregulation of the timing of reproductive events, rather than on the
      alteration of a specific component of the reproductive pathway.

PMID- 14668400
TI  - Partial diploidization of meiosis in autotetraploid Arabidopsis thaliana.
AB  - Meiosis was analyzed cytogenetically in autotetraploids of Arabidopsis, including
      both established lines and newly generated autotetraploid plants. Fluorescent in
      situ hybridization with 5S and 45S rDNA probes was used to identify the different
      chromosomes at metaphase I of meiosis. Multivalents were observed frequently in
      all the lines analyzed, but there were significant differences in multivalent
      frequency not only between the newly generated tetraploids and the established
      lines but also among the different established lines. The new tetraploids showed
      high multivalent frequencies, exceeding the theoretical 66.66% predicted by the
      simple random-end pairing model, in some cases significantly, thus indicating
      that Arabidopsis autotetraploids have more than two autonomous pairing sites per
      chromosome, despite their small sizes. The established lines showed fewer
      multivalents than the new autotetraploids did, but the extent of this reduction
      was strongly line and chromosome dependent. One line in particular showed a large
      reduction in multivalents and a concomitant increase in bivalents, while the
      other lines showed lesser reductions in multivalents. The reduction in
      multivalents was not uniformly distributed across chromosomes. The smaller
      chromosomes, especially chromosomes 2 and 4, showed the most marked reductions
      while the largest chromosome (1) showed virtually no reduction compared to the
      new tetraploids. It is concluded that the established autotetraploid lines have
      undergone a partial diploidization of meiosis, but not necessarily genetical
      diploidization, since their creation. Possible mechanisms for the resulting
      change in meiotic chromosome behavior are discussed.

PMID- 14668401
TI  - Quantitative trait locus analysis of leaf dissection in tomato using Lycopersicon
      pennellii segmental introgression lines.
AB  - Leaves are one of the most conspicuous and important organs of all seed plants. A
      fundamental source of morphological diversity in leaves is the degree to which
      the leaf is dissected by lobes and leaflets. We used publicly available segmental
      introgression lines to describe the quantitative trait loci (QTL) controlling the
      difference in leaf dissection seen between two tomato species, Lycopersicon
      esculentum and L. pennellii. We define eight morphological characteristics that
      comprise the mature tomato leaf and describe loci that affect each of these
      characters. We found 30 QTL that contribute one or more of these characters. Of
      these 30 QTL, 22 primarily affect leaf dissection and 8 primarily affect leaf
      size. On the basis of which characters are affected, four classes of loci emerge
      that affect leaf dissection. The majority of the QTL produce phenotypes
      intermediate to the two parent lines, while 5 QTL result in transgression with
      drastically increased dissection relative to both parent lines.

PMID- 14668402
TI  - A consensus linkage map for sugi (Cryptomeria japonica) from two pedigrees, based
      on microsatellites and expressed sequence tags.
AB  - A consensus map for sugi (Cryptomeria japonica) was constructed by integrating
      linkage data from two unrelated third-generation pedigrees, one derived from a
      full-sib cross and the other by self-pollination of F1 individuals. The progeny
      segregation data of the first pedigree were derived from cleaved amplified
      polymorphic sequences, microsatellites, restriction fragment length
      polymorphisms, and single nucleotide polymorphisms. The data of the second
      pedigree were derived from cleaved amplified polymorphic sequences, isozyme
      markers, morphological traits, random amplified polymorphic DNA markers, and
      restriction fragment length polymorphisms. Linkage analyses were done for the
      first pedigree with JoinMap 3.0, using its parameter set for progeny derived by
      cross-pollination, and for the second pedigree with the parameter set for progeny
      derived from selfing of F1 individuals. The 11 chromosomes of C. japonica are
      represented in the consensus map. A total of 438 markers were assigned to 11
      large linkage groups, 1 small linkage group, and 1 nonintegrated linkage group
      from the second pedigree; their total length was 1372.2 cM. On average, the
      consensus map showed 1 marker every 3.0 cM. PCR-based codominant DNA markers such
      as cleaved amplified polymorphic sequences and microsatellite markers were
      distributed in all linkage groups and occupied about half of mapped loci. These
      markers are very useful for integration of different linkage maps, QTL mapping,
      and comparative mapping for evolutional study, especially for species with a
      large genome size such as conifers.

PMID- 14668403
TI  - Detection and effects of a homeologous reciprocal transposition in Brassica
      napus.
AB  - A reciprocal chromosomal transposition was identified in several annual oilseed
      Brassica napus genotypes used as parents in crosses to biennial genotypes for
      genetic mapping studies. The transposition involved an exchange of interstitial
      homeologous regions on linkage groups N7 and N16, and its detection was made
      possible by the use of segregating populations of doubled haploid lines and
      codominant RFLP markers. RFLP probes detected pairs of homeologous loci on N7 and
      N16 for which the annual and biennial parents had identical alleles in regions
      expected to be homeologous. The existence of an interstitial reciprocal
      transposition was confirmed by cytological analysis of synaptonemal complexes of
      annual x biennial F1 hybrids. Although it included approximately one-third of the
      physical length of the N7 and N16 chromosomes, few recombination events within
      the region were recovered in the progenies of the hybrids. Significantly higher
      seed yields were associated with the parental configurations of the rearrangement
      in segregating progenies. These progenies contained complete complements of
      homeologous chromosomes from the diploid progenitors of B. napus, and thus their
      higher seed yields provide evidence for the selective advantage of allopolyploidy
      through the fixation of intergenomic heterozygosity.

PMID- 14668404
TI  - Detecting population growth, selection and inherited fertility from haplotypic
      data in humans.
AB  - The frequency of a rare mutant allele and the level of allelic association
      between this allele and one or several closely linked markers are frequently
      measured in genetic epidemiology. Both quantities are related to the time elapsed
      since the appearance of the mutation in the population and the intrinsic growth
      rate of the mutation (which may be different from the average population growth
      rate). Here, we develop a method that uses these two kinds of genetic data to
      perform a joint estimation of the age of the mutation and the minimum growth rate
      that is compatible with its present frequency. In absence of demographic data, it
      provides a useful estimate of population growth rate. When such data are
      available, contrasts among estimates from several loci allow demographic
      processes, affecting all loci similarly, to be distinguished from selection,
      affecting loci differently. Testing these estimates on populations for which data
      are available for several disorders shows good congruence with demographic data
      in some cases whereas in others higher growth rates are obtained, which may be
      the result of selection or hidden demographic processes.

PMID- 14668405
TI  - The problem of counting sites in the estimation of the synonymous and
      nonsynonymous substitution rates: implications for the correlation between the
      synonymous substitution rate and codon usage bias.
AB  - Most methods for estimating the rate of synonymous and nonsynonymous substitution
      per site define a site as a mutational opportunity: the proportion of sites that
      are synonymous is equal to the proportion of mutations that would be synonymous
      under the model of evolution being considered. Here we demonstrate that this
      definition of a site can give misleading results and that a physical definition
      of site should be used in some circumstances. We illustrate our point by
      reexamining the relationship between codon usage bias and the synonymous
      substitution rate. It has recently been shown that the rate of synonymous
      substitution, calculated using the Goldman-Yang method, which encapsulates the
      mutational-opportunity definition of a site at a high level of sophistication, is
      either positively correlated or uncorrelated to synonymous codon bias in
      Drosophila. Using other methods, which account for synonymous codon bias but
      define a site physically, we show that there is a negative correlation between
      the synonymous substitution rate and codon bias and that the lack of a negative
      correlation using the Goldman-Yang method is due to the way in which the number
      of synonymous sites is counted. We also show that there is a positive correlation
      between the synonymous substitution rate and third position GC content in
      mammals, but that the relationship is considerably weaker than that obtained
      using the Goldman-Yang method. We argue that the Goldman-Yang method is
      misleading in this context and conclude that methods that rely on a mutational
      opportunity definition of a site should be used with caution.

PMID- 14668406
TI  - Rank-based statistical methodologies for quantitative trait locus mapping.
AB  - This article addresses the identification of genetic loci (QTL and elsewhere)
      that influence nonnormal quantitative traits with focus on experimental crosses.
      QTL mapping is typically based on the assumption that the traits follow normal
      distributions, which may not be true in practice. Model-free tests have been
      proposed. However, nonparametric estimation of genetic effects has not been
      studied. We propose an estimation procedure based on the linear rank test
      statistics. The properties of the new procedure are compared with those of
      traditional likelihood-based interval mapping and regression interval mapping via
      simulations and a real data example. The results indicate that the nonparametric
      method is a competitive alternative to the existing parametric methodologies.

PMID- 14668407
TI  - Chromosome condensation defects in barren RNA-interfered Drosophila cells.
AB  - Barren, the Drosophila homolog of XCAP-H, is one of three non-SMC subunits of
      condensin, a conserved 13S multiprotein complex required for chromosome
      condensation. Mutations in barren (barr) were originally shown to affect sister
      chromatid separation during mitosis 16 of the Drosophila embryo, whereas
      condensation defects were not detected. In contrast, mutations in yeast homologs
      of barren result in defective mitotic chromosome condensation as well as
      irregular chromatid separation. We have used double-stranded RNA-mediated
      interference (RNAi) to deplete Barren in Drosophila S2 cells. Our analyses
      indicate that inactivation of barr leads to extensive chromosome condensation and
      disrupts chromatid segregation.

PMID- 14668408
TI  - Compositional biases and polyalanine runs in humans.
AB  - Human proteins containing polyalanine tracts tend to have runs of other amino
      acids and their open reading frames (ORFs) display a biased codon usage. Their
      alanine, glycine, proline, and histidine content strongly correlates with the GC
      content of the third codon base, suggesting that the compositional specificity of
      these proteins is dictated to a great extent by the evolution of their ORFs.

PMID- 14668409
TI  - Effect of misoriented sites on neutrality tests with outgroup.
AB  - Several neutrality tests use outgroups to infer the ancestral and derived states
      for polymorphism data. However, homoplasy can result in the incorrect inference
      of the derived variant. We show that empirically derived rates of misorientation
      strongly influence Fay and Wu's H-test, especially when the sample size is large.

PMID- 14668410
TI  - The EGL-13 SOX domain transcription factor affects the uterine pi cell lineages
      in Caenorhabditis elegans.
AB  - We isolated egl-13 mutants in which the pi cells of the Caenorhabditis elegans
      uterus initially appeared to develop normally but then underwent an extra round
      of cell division. The data suggest that egl-13 is required for maintenance of the
      pi cell fate.

PMID- 14668411
TI  - Genome-wide germline-enriched and sex-biased expression profiles in
      Caenorhabditis elegans.
AB  - We performed a genome-wide analysis of gene expression in C. elegans to identify
      germline- and sex-regulated genes. Using mutants that cause defects in germ cell
      proliferation or gametogenesis, we identified sets of genes with germline
      enriched expression in either hermaphrodites or males, or in both sexes.
      Additionally, we compared gene expression profiles between males and
      hermaphrodites lacking germline tissue to define genes with sex-biased expression
      in terminally differentiated somatic tissues. Cross-referencing hermaphrodite
      germline and somatic gene sets with in situ hybridization data demonstrates that
      the vast majority of these genes have appropriate spatial expression patterns.
      Additionally, we examined gene expression at multiple times during wild-type
      germline development to define temporal expression profiles for these genes. Sex-
      and germline-regulated genes have a non-random distribution in the genome, with
      especially strong biases for and against the X chromosome. Comparison with data
      from large-scale RNAi screens demonstrates that genes expressed in the oogenic
      germline display visible phenotypes more frequently than expected.

PMID- 14668412
TI  - Caspases function in autophagic programmed cell death in Drosophila.
AB  - Self-digestion of cytoplasmic components is the hallmark of autophagic programmed
      cell death. This auto-degradation appears to be distinct from what occurs in
      apoptotic cells that are engulfed and digested by phagocytes. Although much is
      known about apoptosis, far less is known about the mechanisms that regulate
      autophagic cell death. Here we show that autophagic cell death is regulated by
      steroid activation of caspases in Drosophila salivary glands. Salivary glands
      exhibit some morphological changes that are similar to apoptotic cells, including
      fragmentation of the cytoplasm, but do not appear to use phagocytes in their
      degradation. Changes in the levels and localization of filamentous Actin, alpha
      Tubulin, alpha-Spectrin and nuclear Lamins precede salivary gland destruction,
      and coincide with increased levels of active Caspase 3 and a cleaved form of
      nuclear Lamin. Mutations in the steroid-regulated genes beta FTZ-F1, E93, BR-C
      and E74A that prevent salivary gland cell death possess altered levels and
      localization of filamentous Actin, alpha-Tubulin, alpha-Spectrin, nuclear Lamins
      and active Caspase 3. Inhibition of caspases, by expression of either the caspase
      inhibitor p35 or a dominant-negative form of the initiator caspase Dronc, is
      sufficient to inhibit salivary gland cell death, and prevent changes in nuclear
      Lamins and alpha-Tubulin, but not to prevent the reorganization of filamentous
      Actin. These studies suggest that aspects of the cytoskeleton may be required for
      changes in dying salivary glands. Furthermore, caspases are not only used during
      apoptosis, but also function in the regulation of autophagic cell death.

PMID- 14668413
TI  - Tcf3: a transcriptional regulator of axis induction in the early embryo.
AB  - The roles of Lef/Tcf proteins in determining cell fate characteristics have been
      described in many contexts during vertebrate embryogenesis, organ and tissue
      homeostasis, and cancer formation. Although much of the accumulated work on these
      proteins involves their ability to transactivate target genes when stimulated by
      beta-catenin, Lef/Tcf proteins can repress target genes in the absence of
      stabilized beta-catenin. By ablating Tcf3 function, we have uncovered an
      important requirement for a repressor function of Lef/Tcf proteins during early
      mouse development. Tcf3-/- embryos proceed through gastrulation to form mesoderm,
      but they develop expanded and often duplicated axial mesoderm structures,
      including nodes and notochords. These duplications are preceded by ectopic
      expression of Foxa2, an axial mesoderm gene involved in node specification, with
      a concomitant reduction in Lefty2, a marker for lateral mesoderm. By contrast,
      expression of a beta-catenin-dependent, Lef/Tcf reporter (TOPGal), is not
      ectopically activated but is faithfully maintained in the primitive streak. Taken
      together, these data reveal a unique requirement for Tcf3 repressor function in
      restricting induction of the anterior-posterior axis.

PMID- 14668414
TI  - Multiple roles of Hoxa11 and Hoxd11 in the formation of the mammalian forelimb
      zeugopod.
AB  - Mutations in the 5' or posterior murine Hox genes (paralogous groups 9-13)
      markedly affect the formation of the stylopod, zeugopod and autopod of both
      forelimbs and hindlimbs. Targeted disruption of Hoxa11 and Hoxd11 or Hoxa10,
      Hoxc10 and Hoxd10 result in gross mispatterning of the radius and ulna or the
      femur, respectively. Similarly, in mice with disruptions of both Hoxa13 and
      Hoxd13, development of the forelimb and hindlimb autopod is severely curtailed.
      Although these examples clearly illustrate the major roles played by the
      posterior Hox genes, little is known regarding the stage or stages at which Hox
      transcription factors intersect with the limb development program to ensure
      proper patterning of the principle elements of the limb. Moreover, the cellular
      and/or molecular bases for the developmental defects observed in these mutant
      mice have not been described. In this study, we show that malformation of the
      forelimb zeugopod in Hoxa11/Hoxd11 double mutants is a consequence of
      interruption at multiple steps during the formation of the radius and ulna. In
      particular, reductions in the levels of Fgf8 and Fgf10 expression may be related
      to the observed delay in forelimb bud outgrowth that, in turn, leads to the
      formation of smaller mesenchymal condensations. However, the most significant
      defect appears to be the failure to form normal growth plates at the proximal and
      distal ends of the zeugopod bones. As a consequence, growth and maturation of
      these bones is highly disorganized, resulting in the creation of amorphous bony
      elements, rather than a normal radius and ulna.

PMID- 14668415
TI  - Skeletal development is regulated by fibroblast growth factor receptor 1
      signalling dynamics.
AB  - Ligand-dependent signalling pathways have been characterised as having morphogen
      properties where there is a quantitative relationship between receptor activation
      and response, or threshold characteristics in which there is a binary switch in
      response at a fixed level of receptor activation. Here we report the use of a
      bacterial artificial chromosome (BAC)-based transgenic system in which a
      hypermorphic mutation has been introduced into the murine Fgfr1 gene. These mice
      exhibit cranial suture and sternal fusions that are exacerbated when the BAC copy
      number is increased. Surprisingly, increasing mutant BAC copy number also leads
      to the de novo appearance of digit I polydactyly in the hind limb and
      transformations of the vertebrae. Polydactyly is accompanied by a reduction of
      programmed cell death in the developing hind limb. Candidate gene analysis
      reveals downregulation of Dkk1 in the digit I field and upregulation of Wnt5a and
      Hoxd13. These findings show that Fgfr1-mediated developmental pathways exhibit
      differing signalling dynamics, whereby development of the cranial sutures and
      sternum follows a morphogen mode, whereas development of the vertebral column and
      the hind limbs has threshold signalling properties.

PMID- 14668416
TI  - Advances and contemporary issues in prophylaxis for deep vein thrombosis.

PMID- 14668417
TI  - Temporal trends in prevention of venous thromboembolism following primary total
      hip or knee arthroplasty 1996-2001: findings from the Hip and Knee Registry.
AB  - BACKGROUND: The Hip and Knee Registry is an observational database comprising
      data on practices of US orthopedic surgeons during 1996 to 2001. We examined
      trends in the use of prophylaxis for venous thromboembolism (VTE) among patients
      who underwent primary total hip arthroplasty (THA) or total knee arthroplasty
      (TKA). METHODS: Data on 9,327 THA and 13,846 TKA patients were submitted between
      1996 and 2001 by 464 orthopedic surgeons from 319 hospitals in 42 of the United
      States. RESULTS: During 1996 to 2001, 44% of THA patients and 38% of TKA patients
      were male, and 93% and 92% were white, respectively. The median age of THA and
      TKA patients increased from 66 to 68 years and 68 to 69 years, respectively,
      between 1996 and 2001 (p < 0.001), while the mean length of hospital stay
      decreased from 4.7 to 3.7 days and 4.5 to 3.7 days, respectively (p < 0.001). Use
      of spinal or epidural anesthesia increased from 34 to 46% for THA and 43 to 54%
      for TKA patients (p < 0.001). One or more types of thromboprophylaxis were
      administered to 99% of patients. The following were the most common types of
      thromboprophylaxis: elastic stockings (61% and 58%), warfarin (56% and 53%), low
      molecular-weight heparin (38% and 40%), and intermittent pneumatic compression
      (35% and 32%) in THA and TKA patients, respectively. Aspirin was used for
      thromboprophylaxis in 4% of THA and 7% of TKA patients. One or more type of in
      hospital prophylaxis matching the 2001 American College of Chest Physicians
      (ACCP) recommendations were administered to 89% of THA and 91% of TKA patients
      between 1996 and 2001. During this period, in-hospital use of ACCP prophylaxis
      recommendations increased from 88 to 94% following THA (p < 0.001). This increase
      was also observed for prophylaxis administered to TKA patients, although this did
      not reach statistical significance. CONCLUSIONS: Recent trends in the management
      of patients undergoing THA and TKA in the United States, including shorter
      lengths of hospital stay and increased use of spinal/epidural anesthesia, present
      a challenge to orthopedic surgeons who wish to provide their patients with
      effective prophylaxis for VTE. Despite these challenges, nearly all surgeons
      participating in the Hip and Knee Registry are providing types of prophylaxis
      consistent with evidence-based consensus recommendations. Although there are
      concerns regarding increased bleeding risk due to the use of anticoagulants in
      patients receiving spinal/epidural anesthesia, there was a significant increase
      in the use of spinal/epidural anesthesia between 1996 and 2001. During this same
      period, the proportion of patients receiving spinal/epidural anesthesia who were
      also administered anticoagulants as prophylaxis increased significantly.

PMID- 14668418
TI  - Prevention of venous thromboembolism in the ICU.
AB  - BACKGROUND: Although venous thromboembolism (VTE) is an important cause of
      morbidity and mortality in critical care unit patients, the risk of VTE and its
      prevention have been poorly characterized in this population. Evidence-based
      thromboprophylaxis guidelines are also not available for these critically ill
      patients. OBJECTIVES: To review the prevalence of VTE, to summarize the available
      clinical trials of thromboprophylaxis, and to outline a practical approach to the
      prevention of VTE in critical care unit patients. METHODS: Systematic review of
      the relevant literature. RESULTS: Most patients in critical care units have at
      least one major risk factor for VTE, and many patients have multiple risk
      factors. Objectively confirmed deep-vein thrombosis (DVT) rates varied from 13 to
      31% among the four prospective studies in which critical care unit patients did
      not receive prophylaxis. We were able to identify only three randomized trials of
      thromboprophylaxis conducted in critical care units. The results of these studies
      suggest that both low-dose heparin and low-molecular-weight heparin are
      efficacious in preventing DVT compared with no prophylaxis. Fourteen studies
      reported that compliance with some form of thromboprophylaxis occurred in 33 to
      100% of critically ill patients. CONCLUSIONS: There is a paucity of data
      assessing the risks and prevention of VTE in critical care settings. Selection of
      prophylaxis for these challenging patients involves a consideration of the
      thromboembolic and bleeding risks, both of which may vary in the same patient
      from day to day.

PMID- 14668419
TI  - New pentasaccharides for prophylaxis of deep vein thrombosis: pharmacology.
AB  - Fondaparinux is the first of a new class of antithrombotic compounds, the
      synthetic pentasaccharides. By binding rapidly and strongly to antithrombin, its
      sole physiologic target in plasma, fondaparinux catalyzes specifically the
      inhibition of factor Xa, which results in effective and linear dose-dependent
      inhibition of thrombin generation. Fondaparinux does not bind to platelets. Its
      antithrombotic effect has been demonstrated in several animal models of arterial
      and venous thrombosis. At equivalent antithrombotic concentrations, fondaparinux
      induced less bleeding than unfractionated heparin in experimental bleeding
      models. Furthermore, it did not cross-react with sera from patients with heparin
      induced thrombocytopenia. Administered subcutaneously, the absorption of
      fondaparinux is complete, rapid, and independent of dose. It has a linear
      pharmacokinetic profile, and its half-life of approximately 17 h allows for once
      daily dosing. Fondaparinux is almost completely excreted by the kidneys. Owing to
      the limited intrasubject and intersubject variability, routine monitoring and
      dose adjustments should not be required for most patients. Fondaparinux has been
      approved for use in thromboprophylaxis after major orthopedic surgery, where it
      has demonstrated its efficacy compared to a low-molecular-weight heparin. Its
      clinical development in other indications is ongoing.

PMID- 14668420
TI  - New pentasaccharides for the prophylaxis of venous thromboembolism: clinical
      studies.
AB  - Fondaparinux, a selective inhibitor of factor Xa, is the first of a new class of
      antithrombotic compounds, the synthetic pentasaccharides. Its benefit-to-risk
      ratio in preventing venous thromboembolism after major orthopedic surgery was
      investigated in four randomized, double-blind international phase III trials in
      patients undergoing surgery for hip fracture, elective hip replacement, and major
      knee surgery. Compared to enoxaparin, fondaparinux administered at a subcutaneous
      dose of 2.5 mg qd, starting postoperatively, reduced the overall incidence of
      venous thromboembolism up to day 11 by 55.2% (p < 0.001). The incidence of
      clinically relevant bleeding was low and did not differ between the two groups.
      Overall, fondaparinux achieved optimal efficacy and safety when treatment was
      initiated > or =6 h after the surgical procedure. In a further randomized double
      blind trial, 4 weeks of prophylaxis with fondaparinux after hip fracture surgery
      reduced the risk of venous thromboembolism by 96% as compared to 1 week of
      prophylaxis, and was well tolerated. Fondaparinux has been recently approved for
      use in thromboprophylaxis after major orthopedic surgery. The clinical
      development of fondaparinux in other thromboprophylactic indications is ongoing.

PMID- 14668421
TI  - Controversies in timing of the first dose of anticoagulant prophylaxis against
      venous thromboembolism after major orthopedic surgery.
AB  - Adjusted doses of oral warfarin sodium or fixed doses of subcutaneous low
      molecular-weight heparin (LMWH) are the standard approaches for preventing venous
      thromboembolism following major orthopedic surgery of the legs. In recent years,
      new anticoagulants have been compared with either LMWH or warfarin. The optimal
      timing for the first dose of LMWH prophylaxis and of the new anticoagulants is
      controversial. Recent clinical trials of LMWH and of newer anticoagulants have
      provided new information on the relationship between the timing of the first
      anticoagulant dose and the efficacy and safety of thromboprophylaxis after major
      orthopedic surgery. These data on the optimal timing of initiating prophylaxis
      come from limited direct randomized comparisons of different timing with the same
      anticoagulant, subgroup analysis of large studies with a single anticoagulant,
      indirect comparisons across studies in systematic reviews, and single randomized
      trials comparing different anticoagulants. In the direct comparison of the same
      anticoagulant, preoperative initiation of the same regimen of LMWH (dalteparin)
      increased major bleeding, without improved antithrombotic efficacy compared to
      the early postoperative regimen. Fondaparinux, 2.5 mg, begun 6 h postoperatively
      is more effective and as safe as the currently approved regimens of enoxaparin
      begun either 12 h preoperatively, or 12 to 24 h postoperatively, in patients
      undergoing major orthopedic surgery. In a subgroup analysis of several large
      randomized trials, fondaparinux, 2.5 mg, begun < 6 h postoperatively was
      associated with increased major bleeding, without improved efficacy. The results
      of indirect comparisons also favor the use of a 6-h postoperative starting time
      for the first dose, while the single randomized trials comparing different
      anticoagulants performed to date are not helpful in establishing an optimal time
      for the first dose. The aggregate clinical research evidence supports the
      following general conclusions about the relationship between the timing of the
      first anticoagulant dose and the efficacy and safety of prophylaxis: (1)
      preoperative initiation is not required for good efficacy and, when begun within
      2 h of surgery, increases major bleeding; (2) initiation at 6 h postoperatively
      is effective and not associated with increased major bleeding; (3) initiation < 6
      h postoperatively increases major bleeding, without improved efficacy; thus, 6 h
      appears to be the threshold for early postoperative administration; and (4)
      initiation 12 to 24 h postoperatively may be less effective than initiation at 6
      h, but further randomized trials comparing the same anticoagulant initiated at
      different times postoperatively (eg, 6 h vs 12 h) are required to establish
      definitively the optimal timing of the first anticoagulant dose.

PMID- 14668422
TI  - Duration of venous thromboembolism prophylaxis after surgery.
AB  - Venous thromboembolism (VTE) prophylaxis is indicated while in the hospital after
      major surgery. There is evidence that the prevalence of asymptomatic deep-vein
      thrombosis, detected by routine venography after major orthopedic surgery, is
      lower at hospital discharge in patients who have received 10 days rather than 5
      days of prophylaxis. This observation supports the current American College of
      Chest Physicians (ACCP) recommendation for a minimum of 7 to 10 days of
      prophylaxis after hip and knee replacement, even if patients are discharged from
      the hospital within 7 days of surgery. As risk of VTE persists for up to 3 months
      after surgery, patients at high risk for postoperative VTE may benefit from
      extended prophylaxis (eg, an additional 3 weeks after the first 7 to 10 days).
      Extended prophylaxis with low-molecular-weight heparin (LMWH) reduces the
      frequency of postdischarge VTE by approximately two thirds after hip replacement;
      however, the resultant absolute reduction in the frequency of fatal pulmonary
      embolism is small (ie, estimated at 1 per 2,500 patients). Indirect evidence
      suggests that, compared with LMWH, efficacy of extended prophylaxis after hip
      replacement is greater with fondaparinux, similar with warfarin, and less with
      aspirin. Extended prophylaxis is expected to be of less benefit after knee than
      after hip replacement. In keeping with current ACCP recommendations, at a
      minimum, extended prophylaxis should be used after major orthopedic surgery in
      patients who have additional risk factors for VTE (eg, previous VTE, cancer). If
      anticoagulant drug therapy is stopped after 7 to 10 days, an additional month of
      prophylaxis with aspirin should be considered.

PMID- 14668423
TI  - The economics of venous thromboembolism prophylaxis: a primer for clinicians.
AB  - Cost-effectiveness information can help health-system participants make decisions
      about diagnostic or therapeutic innovations that are more expensive but
      incrementally safe and effective. However, these analyses cannot help decide
      whether a less expensive approach is "sufficient" and funds ought to be allocated
      to other medical issues entirely. At present, formulary committees are commonly
      determining that medications are "mostly equivalent" in efficacy and safety and
      choosing individual medications or classes of medications based on cost.
      Clinicians may not agree with these decisions and will need to understand their
      rationale. For prophylaxis of venous thromboembolism after hip and knee
      replacement and hip fracture surgery, many preventive modalities are available
      with different safety and efficacy profiles and different costs. It is possible
      to list the important safety and efficacy outcomes of prophylaxis, estimate their
      incidences and costs, and "model" comparisons of one modality vs another, in
      order to help decide whether one is preferable.

PMID- 14668424
TI  - Mission (not) impossible. Endocrinologist Nir Barzilai, a former chief instructor
      of medics for the Israeli army, is determined to elucidate the relations among
      body fat, blood lipids, insulin, and aging.

PMID- 14668425
TI  - Can new neurons replace memories lost?
AB  - It now appears that new neurons are produced not only in the healthy adult brain
      but also in the brains of patients with Alzheimer's disease (AD). Although the
      function of new neurons in the healthy brain is unknown, there is evidence that
      they are involved in certain types of memory formation and that their survival is
      enhanced dramatically and persistently by learning experiences. The evidence that
      neurogenesis, or at least the expression of proteins unique to immature neurons,
      occurs during the late stages of AD raises the possibility that their production
      could be enhanced earlier in the disease process before so many neurons and
      memories are lost.

PMID- 14668426
TI  - MR quantification of hepatic iron concentration.
AB  - PURPOSE: To evaluate the accuracy of magnetic resonance (MR) imaging in the
      quantification of hepatic iron concentration. MATERIALS AND METHODS: Between
      April 1999 and June 2001, 112 patients were recruited prospectively. All had
      undergone liver biopsy and hepatic iron concentration quantification with
      spectrophotometry, followed by MR imaging. MR imaging involved use of four
      gradient-echo sequences and one spin-echo sequence. Signal intensity (SI) was
      measured on images obtained with each sequence by means of regions of interest
      placed in the liver and paraspinal muscle to obtain the liver-to-muscle SI ratio.
      The relationship between hepatic iron concentration and SI ratio for each
      sequence was analyzed with multiple linear regression. Receiver operating
      characteristic analysis was performed to find the diagnostic thresholds. RESULTS:
      Sixty-eight patients had normal hepatic iron levels (<36 micromol/g), 23 had
      hemosiderosis (36-80 micromol/g), and 21 had hemochromatosis (>80 micromol/g).
      With all sequences, an inverse linear relationship between iron concentration and
      SI ratio was apparent. The authors generated a mathematic model to estimate the
      iron concentrations from MR imaging data (r = 0.937). For estimated
      concentrations of more than 85 micromol/g, the positive predictive value for
      hemochromatosis was 100%; for those less than 40 micromol/g, the negative
      predictive value for hemochromatosis was 100%. For estimated concentrations of
      more than 58 micromol/g, the positive predictive value for iron overload was
      100%; for those less than 20 micromol/g, the negative predictive value for iron
      overload was 100%. CONCLUSION: MR imaging is a useful and noninvasive diagnostic
      tool for quantification of hepatic iron concentration.

PMID- 14668427
TI  - Variations in calcaneonavicular morphology demonstrated with radiography.
AB  - PURPOSE: To determine and classify radiographically demonstrated variations in
      calcaneonavicular morphology and to estimate prevalence in a clinically relevant
      patient population. MATERIALS AND METHODS: Retrospective review was performed of
      foot radiographs obtained during diagnostic evaluation of 460 consecutive
      patients who presented to the emergency department with acute foot pain.
      Variations in calcaneonavicular morphology depicted on the medial oblique view
      (obtained at a 45 degrees angle) were classified into four groups according to
      morphologic type (types 1-4), and the prevalence of each type was calculated.
      Chi2 analysis was used to compare the prevalence of each type in male patients
      and in female patients. One-way analyses of variance were used to compare mean
      ages of patients for each type and mean calcaneonavicular gaps for each type.
      RESULTS: The prevalence of morphologic types 1, 2, and 3 was 94.3%, 2.8%, and
      2.8%, respectively. The combined prevalence of types 2 and 3 (calcaneonavicular
      coalitions produced by synchondrosis and syndesmosis, respectively) was 5.6% (95%
      CI: 3.5%, 7.8%). There were no patients with type 4 morphology (synostosis). The
      numbers of male patients and female patients with morphologic types 1-3 were
      approximately equal (P =.9), and there was no statistically significant
      correlation between any of these three morphologic types and patient age (P =.2).
      The calcaneonavicular gap was significantly narrower in types 2 and 3 than in
      type 1 (P =.01), which was characterized as the normal morphology. CONCLUSION:
      The general prevalence of calcaneonavicular coalition (synchondrosis and
      syndesmosis) may be greater than previously reported, but further research is
      needed to prove the validity of this hypothesis.

PMID- 14668428
TI  - Multi-detector row CT of left ventricular function with dedicated analysis
      software versus MR imaging: initial experience.
AB  - PURPOSE: To determine left ventricular (LV) volumetric and functional parameters
      from retrospectively electrocardiographically gated multi-detector row computed
      tomography (CT) by using semiautomated analysis software and to correlate results
      with those of magnetic resonance (MR) imaging. MATERIALS AND METHODS: In 30
      patients (mean age, 59.2 years +/- 7.1 [SD]) known to have or suspected of having
      coronary artery disease, four-channel multi-detector row CT was performed with
      standard technique, and diastolic and systolic image reconstructions were
      generated. With commercially available analysis software capable of semiautomated
      contour detection, end diastolic and end systolic LV volumes were determined from
      short-axis secondary CT reformations. Steady-state free-precession cine MR images
      were acquired in short-axis orientation within 48 hours and analyzed by using
      dedicated software. Bland-Altman analysis was performed to calculate limits of
      agreement and systematic errors between CT and MR imaging. RESULTS: Mean end
      diastolic (138.8 mL +/- 31.9) and end systolic (53.9 mL +/- 21.2) LV volumes as
      determined with CT correlated well with MR imaging measurements (142.0 mL +/-
      32.5 [r = 0.93] and 54.9 mL +/- 22.8 [r = 0.94], respectively [P <.001]). LV
      ejection fraction (61.6% +/- 10.6 for CT vs 62.3% +/- 10.1 for MR imaging; r =
      0.89) and stroke volume (84.6 mL +/- 20.9 for CT vs 86.9 mL +/- 21.5 for MR
      imaging; r = 0.88) also showed good correlation (P <.001). Bland-Altman analysis
      showed acceptable limits of agreement (+/-9.8% for ejection fraction) without
      systematic errors. CONCLUSION: In selected patients, semiautomated analysis
      software enables LV volumetric and functional analysis based on multi-detector
      row CT data sets, the results of which correlate well with MR imaging findings.

PMID- 14668429
TI  - Cell surface expression of an endoplasmic reticulum resident heat shock protein
      gp96 triggers MyD88-dependent systemic autoimmune diseases.
AB  - Heat shock proteins have been implicated as endogenous activators for dendritic
      cells (DCs). Without tissue distress or death, these intracellular molecules are
      inaccessible to surface receptor(s) on DCs, possibly to avoid uncontrolled DC
      activation and breakdown of immunologic tolerance. We herein addressed this
      hypothesis in transgenic mice by enforcing cell surface expression of gp96, a
      ubiquitous heat shock protein of the endoplasmic reticulum. Although a pan
      specific promoter is used for transgene expression, neither the expression level
      nor the tissue distribution of the endogenous gp96 was altered by this maneuver.
      However, cell surface gp96 induced significant DC activations and spontaneous
      lupus-like autoimmune diseases, even though the development/functions of
      lymphocytic compartments were unaltered. Using a bone marrow chimera approach, we
      further demonstrated that both DC activation and autoimmunity elicited by cell
      surface gp96 are dependent on the downstream adaptor protein MyD88 for signaling
      by Toll/IL-1 receptor family. Our study not only established the proinflammatory
      property of cell surface gp96 in vivo, but also suggested a chronic stimulation
      of DCs by gp96 as a pathway to initiate spontaneous autoimmune diseases.

PMID- 14668430
TI  - Trophoblast expression of fms-like tyrosine kinase 1 is not required for the
      establishment of the maternal-fetal interface in the mouse placenta.
AB  - Fms-like tyrosine kinase 1 (Flt1)/vascular endothelial growth factor (VEGF)
      receptor 1, a receptor for VEGF-A and placental growth factor, is expressed in
      the spongiotrophoblast layer that segregates the maternal and fetal vasculature
      in the mouse placenta. A soluble form of Flt1 (sFlt1) produced in the mouse and
      human placenta can also be detected in the maternal blood. Levels of maternal
      sFlt1 are elevated in preeclampsia, suggesting that placental sFlt1 plays roles
      in regulating the maternal vasculature during pregnancy. However, it remains to
      be determined whether placental Flt1/sFlt1 serves as a regulator of VEGF-A
      activity in the placenta per se. Here, we investigated the placental development
      in Flt1-deficient mice. Flt1 is expressed in a subpopulation of ectoplacental
      cone cells and later marks the spongiotrophoblast cells, peri/endovascular
      trophoblast cells, and trophoblast glycogen cells. The labyrinth of Flt1lacZ/lacZ
      placentae lacked the fetal capillary network because of a defect in allantoic
      mesoderm invasion. To address whether the absence of Flt1 in the trophoblast
      alone affects placental development, we investigated chimeric placentae comprised
      of Flt1lacZ/lacZ trophoblast and Flt1+/+ mesoderm, generated by tetraploid
      aggregation. Fetal growth was supported normally, and no defect in the formation
      of placental circulation into the maternal spiral artery or invasion of
      peri/endovascular trophoblast was detected. These findings indicate that
      trophoblast-derived Flt1/sFlt1 is dispensable for the initial establishment of
      the maternal-fetal interface in the mouse placenta. Targeting maternal sFlt1
      levels for treatment of preeclampsia may thus be possible without affecting the
      proper formation of the placenta.

PMID- 14668431
TI  - Unstable mutants in the peripheral endosomal membrane component ALS2 cause early
      onset motor neuron disease.
AB  - Mutations in ALS2, carrying three putative guanine exchange factor (GEF) domains,
      are causative for a juvenile, autosomal recessive form of amyotrophic lateral
      sclerosis (ALS), primary lateral sclerosis, and infantile-ascending hereditary
      spastic paralysis. Endogenous ALS2 is shown here to be enriched in nervous tissue
      and to be peripherally bound to the cytoplasmic face of endosomal membranes, an
      association that requires the amino-terminal "RCC1 (regulator of chromatin
      condensation)-like" GEF domain. Disease-causing mutants and a naturally truncated
      isoform of ALS2 are shown to be rapidly degraded when expressed in cultured human
      cells, including lymphocytes derived from patients with ALS2 mutations. Thus,
      mutations in the ALS2 gene linked to early-onset motor neuron disease uniformly
      produce loss of activity through decreased protein stability of this endosomal
      GEF.

PMID- 14668432
TI  - Electron tomography analysis of envelope glycoprotein trimers on HIV and simian
      immunodeficiency virus virions.
AB  - We used electron tomography to directly visualize trilobed presumptive envelope
      (env) glycoprotein structures on the surface of negatively stained HIV type 1
      (HIV-1) and simian immunodeficiency virus (SIV) virions. Wild-type HIV-1 and SIV
      virions had an average of 8-10 trimers per virion, consistent with predictions
      based on biochemical evidence. Mutant SIVs, biochemically demonstrated to contain
      high levels of the viral env proteins, averaged 70-79 trimers per virion in
      tomograms. These correlations strongly indicate that the visualized trimers
      represent env spikes. The env trimers were without obvious geometric distribution
      pattern or preferred rotational orientation. Combined with biochemical analysis
      of gag/env ratios in virions, these trimer counts allow calculation of the number
      of gag molecules per virion, yielding an average value of approximately 1400.
      Virion and env dimensions were also determined. Image-averaging analysis of SIV
      env trimers revealed a distinct chirality and strong concordance with recent
      molecular models. The results directly demonstrate the presence of env trimers on
      the surface of AIDS virus virions, albeit at numbers much lower than generally
      appreciated, and have important implications for understanding virion formation,
      virus interactions with host cells, and virus neutralization.

PMID- 14668434
TI  - Channel gating forces govern accuracy of mechano-electrical transduction in hair
      cells.
AB  - Sensory hair cells are known for the exquisite displacement sensitivity with
      which they detect the sound-evoked vibrations in the inner ear. In this article,
      we determine a stochastically imposed fundamental lower bound on a hair cell's
      sensitivity to detect mechanically coded information arriving at its hair bundle.
      Based on measurements of transducer current and its noise in outer hair cells and
      the application of estimation theory, we show that a hair cell's transducer
      current carries information that allows the detection of vibrational amplitudes
      with an accuracy on the order of nanometers. We identify the transducer channel's
      molecular gating force as the physical factor controlling this accuracy in
      proportion to the inverse of its magnitude. Further, we show that the match of
      stochastic channel noise to gating-spring noise implies that the gating apparatus
      operates at the threshold of negative stiffness.

PMID- 14668433
TI  - Abnormal surface liquid pH regulation by cultured cystic fibrosis bronchial
      epithelium.
AB  - Cystic fibrosis (CF) transmembrane conductance regulator (CFTR)-dependent airway
      epithelial bicarbonate transport is hypothesized to participate in airway surface
      liquid pH regulation and contribute to lung defense. We measured pH and ionic
      composition in apical surface liquid (ASL) on polarized normal (NL) and CF
      primary bronchial epithelial cell cultures under basal conditions, after cAMP
      stimulation, and after challenge with luminal acid loads. Under basal conditions,
      CF epithelia acidified ASL more rapidly than NL epithelia. Two ASL pH regulatory
      paths that contributed to basal pH were identified in the apical membrane of
      airway epithelia, and their activities were measured. We detected a ouabain
      sensitive (nongastric) H+,K+-ATPase that acidified ASL, but its activity was not
      different in NL and CF cultures. We also detected the following evidence for a
      CFTR-dependent HCO3- secretory pathway that was defective in CF: (i). ASL [HCO3-]
      was higher in NL than CF ASL; (ii). activating CFTR with forskolin/3-isobutyl-1
      methylxanthine alkalinized NL ASL but acidified CF ASL; and (iii). NL airway
      epithelia more rapidly and effectively alkalinized ASL in response to a luminal
      acid challenge than CF epithelia. We conclude that cultured human CF bronchial
      epithelial pHASL is abnormally regulated under basal conditions because of absent
      CFTR-dependent HCO3- secretion and that this defect can lead to an impaired
      capacity to respond to airway conditions associated with acidification of ASL.

PMID- 14668435
TI  - Leukocyte-inspired biodegradable particles that selectively and avidly adhere to
      inflamed endothelium in vitro and in vivo.
AB  - We exploited leukocyte-endothelial cell adhesion chemistry to generate
      biodegradable particles that exhibit highly selective accumulation on inflamed
      endothelium in vitro and in vivo. Leukocyte-endothelial cell adhesive particles
      exhibit up to 15-fold higher adhesion to inflamed endothelium, relative to
      noninflamed endothelium, under in vitro flow conditions similar to that present
      in blood vessels, a 6-fold higher adhesion to cytokine inflamed endothelium
      relative to non-cytokine-treated endothelium in vivo, and a 10-fold enhancement
      in adhesion to trauma-induced inflamed endothelium in vivo due to the addition of
      a targeting ligand. The leukocyte-inspired particles have adhesion efficiencies
      similar to that of leukocytes and were shown to target each of the major
      inducible endothelial cell adhesion molecules (E-selectin, P-selectin, vascular
      cell adhesion molecule 1, and intercellular adhesion molecule 1) that are up
      regulated at sites of pathological inflammation. The potential for targeted drug
      delivery to inflamed endothelium has significant implications for the improved
      treatment of an array of pathologies, including cardiovascular disease,
      arthritis, inflammatory bowel disease, and cancer.

PMID- 14668436
TI  - Donation of catalytic residues to RNA polymerase active center by transcription
      factor Gre.
AB  - During transcription elongation, RNA polymerase (RNAP) occasionally loses its
      grip on the growing RNA end and backtracks on the DNA template. Prokaryotic Gre
      factors rescue the backtracked ternary elongating complex through stimulation of
      an intrinsic endonuclease activity, which removes the disengaged 3' RNA segment.
      By using RNA-protein crosslinking in defined ternary elongating complexes, site
      directed mutagenesis, discriminative biochemical assays, and docking of the two
      protein structures, we show that Gre acts by providing two carboxylate residues
      for coordination of catalytic Mg2+ ion in the RNAP active center. A similar
      mechanism is suggested for the functionally analogous eukaryotic SII factor. The
      results expand the general two-metal model of RNAP catalytic mechanism whereby
      one of the Mg2+ ions is permanently retained, whereas the other is recruited ad
      hoc by an auxiliary factor.

PMID- 14668437
TI  - The Drosophila homolog of Down's syndrome critical region 1 gene regulates
      learning: implications for mental retardation.
AB  - Mental retardation is the most common phenotypic abnormality seen in Down's
      syndrome (DS) patients, yet the underlying mechanism remains mysterious. DS
      critical region 1 (DSCR1), located on chromosome 21, is overexpressed in the
      brain of DS fetus and encodes an inhibitor of calcineurin, but its physiological
      significance is unknown. To study its functional importance and role in mental
      retardation in DS, we generated Drosophila mutants of nebula, an ortholog of
      human DSCR1. Here, we report that both nebula loss-of-function and overexpression
      mutants exhibit severe learning defects that are attributed by biochemical
      perturbations rather than maldevelopment of the brain. These results, combined
      with our data showing that the same biochemical signaling pathway is altered in
      human DS fetal brain tissue overexpressing DSCR1, suggest that alteration of
      DSCR1 expression could contribute to mental retardation in DS.

PMID- 14668438
TI  - Contribution of transient receptor potential channels to the control of GABA
      release from dendrites.
AB  - Neuronal dendrites have been shown to actively contribute to synaptic information
      transfer through the Ca2+-dependent release of neurotransmitter, although the
      underlying mechanisms remain elusive. This study shows that the increase in
      dendritic gamma-aminobutyric acid (GABA) release from thalamic interneurons
      mediated by the activation of 5-hydroxytryptamine type 2 receptors requires Ca2+
      entry that does not involve Ca2+ release nor voltage-gated Ca2+ channels in the
      plasma membrane but that is critically dependent on the transient receptor
      potential (TRP) protein TRPC4. These data ascribe a functional role of agonist
      activated TRP channels to the release of transmitters from dendrites, thereby
      indicating a principle underlying synaptic interactions in the brain.

PMID- 14668439
TI  - An efficient proteomics method to identify the cellular targets of protein kinase
      inhibitors.
AB  - Small molecule inhibitors of protein kinases are widely used in signal
      transduction research and are emerging as a major class of drugs. Although
      interpretation of biological results obtained with these reagents critically
      depends on their selectivity, efficient methods for proteome-wide assessment of
      kinase inhibitor selectivity have not yet been reported. Here, we address this
      important issue and describe a method for identifying targets of the widely used
      p38 kinase inhibitor SB 203580. Immobilization of a suitable SB 203580 analogue
      and thoroughly optimized biochemical conditions for affinity chromatography
      permitted the dramatic enrichment and identification of several previously
      unknown protein kinase targets of SB 203580. In vitro kinase assays showed that
      cyclin G-associated kinase (GAK) and CK1 were almost as potently inhibited as
      p38alpha whereas RICK [Rip-like interacting caspase-like apoptosis-regulatory
      protein (CLARP) kinase/Rip2/CARDIAK] was even more sensitive to inhibition by SB
      203580. The cellular kinase activity of RICK, a known signal transducer of
      inflammatory responses, was already inhibited by submicromolar concentrations of
      SB 203580 in intact cells. Therefore, our results warrant a reevaluation of the
      vast amount of data obtained with SB 203580 and might have significant
      implications on the development of p38 inhibitors as antiinflammatory drugs.
      Based on the procedures described here, efficient affinity purification
      techniques can be developed for other protein kinase inhibitors, providing
      crucial information about their cellular modes of action.

PMID- 14668440
TI  - Imaging linear birefringence and dichroism in cerebral amyloid pathologies.
AB  - New advances in polarized light microscopy were used to image Congo red-stained
      cerebral amyloidosis in sharp relief. The rotating-polarizer method was used to
      separate the optical effects of transmission, linear birefringence, extinction,
      linear dichroism, and orientation of the electric dipole transition moments and
      to display them as false-color maps. These effects are typically convolved in an
      ordinary polarized light microscope. In this way, we show that the amyloid
      deposits in Alzheimer's disease plaques contain structurally disordered centers,
      providing clues to mechanisms of crystallization of amyloid in vivo. Comparisons
      are made with plaques from tissues of subjects having Down's syndrome and a prion
      disease. In plaques characteristic of each disease, the Congo red molecules are
      oriented radially. The optical orientation in amyloid deposited in blood vessels
      from subjects having cerebral amyloid angiopathy was 90 degrees out of phase from
      that in the plaques, suggesting that the fibrils run tangentially with respect to
      the circumference of the blood vessels. Our result supports an early model in
      which Congo red molecules are aligned along the long fiber axis and is in
      contrast to the most recent binding models that are based on computation. This
      investigation illustrates that the latest methods for the optical analysis of
      heterogeneous substances are useful for in situ study of amyloid.

PMID- 14668441
TI  - Structural basis for PAS domain heterodimerization in the basic helix--loop-
      helix-PAS transcription factor hypoxia-inducible factor.
AB  - Biological responses to oxygen availability play important roles in development,
      physiological homeostasis, and many disease processes. In mammalian cells, this
      adaptation is mediated in part by a conserved pathway centered on the hypoxia
      inducible factor (HIF). HIF is a heterodimeric protein complex composed of two
      members of the basic helix-loop-helix Per-ARNT-Sim (PAS) (ARNT, aryl hydrocarbon
      receptor nuclear translocator) domain family of transcriptional activators,
      HIFalpha and ARNT. Although this complex involves protein-protein interactions
      mediated by basic helix-loop-helix and PAS domains in both proteins, the role
      played by the PAS domains is poorly understood. To address this issue, we have
      studied the structure and interactions of the C-terminal PAS domain of human HIF
      2alpha by NMR spectroscopy. We demonstrate that HIF-2alpha PAS-B binds the
      analogous ARNT domain in vitro, showing that residues involved in this
      interaction are located on the solvent-exposed side of the HIF-2alpha central
      beta-sheet. Mutating residues at this surface not only disrupts the interaction
      between isolated PAS domains in vitro but also interferes with the ability of
      full-length HIF to respond to hypoxia in living cells. Extending our findings to
      other PAS domains, we find that this beta-sheet interface is widely used for both
      intra- and intermolecular interactions, suggesting a basis of specificity and
      regulation of many types of PAS-containing signaling proteins.

PMID- 14668442
TI  - Juvenile emotional experience alters synaptic composition in the rodent cortex,
      hippocampus, and lateral amygdala.
AB  - A quantitative anatomical study in the rodent anterior cingulate and
      somatosensory cortex, hippocampus, and lateral amygdala revealed region-, cell-,
      and dendrite-specific changes of spine densities in 3-week-old Octodon degus
      after repeated parental separation. In parentally separated animals significantly
      higher spine densities were found on the apical and basal dendrites of the
      cingulate cortex (up to 143% on apical and 138% on basal dendrite). Branching
      order analysis revealed that this effect is seen on all segments of the apical
      dendrite, whereas on the basal dendrites significantly higher spine densities
      were seen only on the outer branches (third to fifth dendritic segments).
      Increased spine densities were also observed on the hippocampal CA1 pyramidal
      neurons (up to 109% on the distal apical segments and up to 106% on the basal
      segment) compared with the control group. In contrast, significantly reduced
      spine densities were observed on the granule cell dendrites in the dentate gyrus
      (down to 92%) and on the apical dendrites in the medial nucleus of the amygdala
      (down to 95%). No significant changes of spine densities were seen in the
      somatosensory cortex (except for an increase in the proximal apical segments) and
      in the lateral nucleus of the dorsal amygdala (except for an increase in the
      proximal basal dendritic segments). These results demonstrate that repeated
      stressful emotional experience alters the balance of presumably excitatory
      synaptic inputs of pyramidal neurons in the limbic system. Such experience
      induced modulations of limbic circuits may determine psychosocial and cognitive
      capacities during later life.

PMID- 14668443
TI  - Rapid protein fold determination using unassigned NMR data.
AB  - Experimental structure determination by x-ray crystallography and NMR
      spectroscopy is slow and time-consuming compared with the rate at which new
      protein sequences are being identified. NMR spectroscopy has the advantage of
      rapidly providing the structurally relevant information in the form of unassigned
      chemical shifts (CSs), intensities of NOESY crosspeaks [nuclear Overhauser
      effects (NOEs)], and residual dipolar couplings (RDCs), but use of these data are
      limited by the time and effort needed to assign individual resonances to specific
      atoms. Here, we develop a method for generating low-resolution protein structures
      by using unassigned NMR data that relies on the de novo protein structure
      prediction algorithm, rosetta [Simons, K. T., Kooperberg, C., Huang, E. & Baker,
      D. (1997) J. Mol. Biol. 268, 209-225] and a Monte Carlo procedure that searches
      for the assignment of resonances to atoms that produces the best fit of the
      experimental NMR data to a candidate 3D structure. A large ensemble of models is
      generated from sequence information alone by using rosetta, an optimal assignment
      is identified for each model, and the models are then ranked based on their fit
      with the NMR data assuming the identified assignments. The method was tested on
      nine protein sequences between 56 and 140 amino acids and published CS, NOE, and
      RDC data. The procedure yielded models with rms deviations between 3 and 6 A,
      and, in four of the nine cases, the partial assignments obtained by the method
      could be used to refine the structures to high resolution (0.6-1.8 A) by repeated
      cycles of structure generation guided by the partial assignments, followed by
      reassignment using the newly generated models.

PMID- 14668444
TI  - An oxocarbenium-ion intermediate of a ribozyme reaction indicated by kinetic
      isotope effects.
AB  - Many of the enzymes that catalyze reactions at nucleotide glycosidic linkages
      proceed through either a reactive oxocarbenium-ion intermediate or a transition
      state with considerable oxocarbenium character. To investigate how an RNA active
      site deals with the catalytic challenge of nucleotide synthesis, we probed the
      transition state of a ribozyme able to promote the formation of a pyrimidine
      nucleotide. Primary and secondary kinetic isotope effects indicate that this
      ribozyme stabilizes a highly dissociative reaction with considerable sp2
      hybridization and negligible bond order between the departing pyrophosphate
      leaving group and the anomeric carbon. The small primary 13C isotope effect of
      1.002 +/- 0.003 indicates that the reaction is likely to be less concerted than
      that observed for protein nucleotide synthesis enzymes, which typically have
      primary 13C isotope effects of 1.02-1.03. The dissociative nature of the ribozyme
      reaction most resembles the reaction of some hydrolytic enzymes, such as uracil
      DNA glycosylase, which uses the negative charges found in the phosphodiester
      backbone of its DNA substrate to transiently stabilize an oxocarbenium ion during
      hydrolysis. The detectable hydrolysis observed in the ribozyme reaction indicates
      that shielding of this reactive intermediate from water is a significant
      challenge for RNA, which protein enzymes that synthesize nucleotides have managed
      to overcome during evolution, apparently by the utilization of more concerted
      chemistry.

PMID- 14668445
TI  - Positional cloning and characterization of Mei1, a vertebrate-specific gene
      required for normal meiotic chromosome synapsis in mice.
AB  - The mouse meiotic mutant Mei1 was isolated in a screen for infertile mice
      descended from chemically mutagenized embryonic stem cells. Homozygotes of both
      sexes are sterile due to meiotic arrest caused by defects in chromosome synapsis.
      Notably, RAD51 protein does not load onto Mei1 mutant meiotic chromosomes,
      suggesting that there is a defect in either recombinational repair or the
      production of double-strand breaks (DSBs) that require such repair. Here, we show
      that treatment of mutant males with cisplatin restores RAD51 loading, suggesting
      that mutant spermatocytes have intact recombinational repair mechanisms. Levels
      of histone H2AX phosphorylation (gammaH2AX) at leptonema are significantly
      reduced compared with wild-type controls but comparable to that seen in animals
      deficient for SPO11, the molecule required for catalyzing DSB formation during
      meiosis. These observations provide evidence that genetically programmed DSB
      induction is defective in Mei1 leptotene spermatocytes. We also report the
      positional cloning of Mei1, which encodes a product without significant homology
      to any known protein. Expressed almost exclusively in gonads, Mei1 has no
      apparent homologs in yeast, worms, or flies. However, Mei1 orthologs are present
      in the genomes of mammals, chickens, and zebrafish. Thus, Mei1 is required for
      vertebrate meiosis. To our knowledge, Mei1 is the first meiosis-specific mutation
      identified by forward genetic approaches in mammals.

PMID- 14668446
TI  - Single-molecule fluorescence resonance energy transfer reveals a dynamic
      equilibrium between closed and open conformations of syntaxin 1.
AB  - Protein conformational transitions form the molecular basis of many cellular
      processes, such as signal transduction and membrane traffic. However, in many
      cases, little is known about their structural dynamics. Here we have used dynamic
      single-molecule fluorescence to study at high time resolution, conformational
      transitions of syntaxin 1, a soluble N-ethylmaleimide-sensitive factor attachment
      protein receptors protein essential for exocytotic membrane fusion. Sets of
      syntaxin double mutants were randomly labeled with a mix of donor and acceptor
      dye and their fluorescence resonance energy transfer was measured. For each set,
      all fluorescence information was recorded simultaneously with high time
      resolution, providing detailed information on distances and dynamics that were
      used to create structural models. We found that free syntaxin switches between an
      inactive closed and an active open configuration with a relaxation time of 0.8
      ms, explaining why regulatory proteins are needed to arrest the protein in one
      conformational state.

PMID- 14668447
TI  - Disruption of hepatitis C virus RNA replication through inhibition of host
      protein geranylgeranylation.
AB  - Hepatitis C virus (HCV) RNA replication depends on viral protein association with
      intracellular membranes, but the influence of membrane composition on viral
      replication is unclear. We report that HCV RNA replication and assembly of the
      viral replication complex require geranylgeranylation of one or more host
      proteins. In cultured hepatoma cells, HCV RNA replication was disrupted by
      treatment with lovastatin, an inhibitor of 3-hydroxy-3-methyglutaryl CoA
      reductase, or with an inhibitor of protein geranylgeranyl transferase I, each of
      which induced the dissolution of the HCV replication complex. Viral replication
      was not affected by treatment of cells with an inhibitor of farnesyl transferase.
      When added to lovastatin-treated cells, geranylgeraniol, but not farnesol,
      restored replication complex assembly and viral replication. Inasmuch as the HCV
      genome does not encode a canonical geranylgeranylated protein, the data suggest
      the involvement of a geranylgeranylated host protein in HCV replication.
      Inhibition of its geranylgeranylation affords a therapeutic strategy for
      treatment of HCV infection.

PMID- 14668448
TI  - Migration and differentiation of neural precursor cells can be directed by
      microglia.
AB  - Recent reports have supported the existence of neural stem cells in the adult
      mammalian CNS. Important features of such cells are self-renewal and
      multipotency, i.e., they can give rise to neurons, astrocytes, and
      oligodendrocytes and thus in principle replace lost cells in the CNS.
      Observations in several animal models of CNS diseases have shown that by unknown
      mechanisms endogenous as well as exogenous precursor cells preferentially migrate
      to damaged areas. Microglia are immunoreactive cells of nonneural lineage
      resident in the CNS. After injury to the CNS, microglia are rapidly activated and
      found concentrated at the sites of injury. In the present article we show, in two
      different assays, that soluble factors released from mouse microglial cells
      direct the migration of neural CNS precursor cells. We also provide evidence that
      microglia have the capacity to influence the differentiation of both adult and
      embryonic neural precursor cells toward a neuronal phenotype. Given that an
      invariant feature of pathological processes in CNS is the activation of
      microglia, these results indicate an important and unique role for microglia in
      directing the replacement of damaged or lost cells in the CNS.

PMID- 14668451
TI  - The discovery of HIV as the cause of AIDS.

PMID- 14668449
TI  - Use of Sindbis virus-mediated RNA interference to demonstrate a conserved role of
      Broad-Complex in insect metamorphosis.
AB  - The transcription factor Broad-Complex (BR-C) is required for differentiation of
      adult structures as well as for the programmed death of obsolete larval organs
      during metamorphosis of the fruit fly Drosophila melanogaster. Whether BR-C has a
      similar role in other holometabolous insects could not be proven without a loss
      of-function genetic test, performed in a non-drosophilid species. Here we use a
      recombinant Sindbis virus as a tool to silence BR-C expression in the silkmoth
      Bombyx mori. The virus expressing a BR-C antisense RNA fragment reduced
      endogenous BR-C mRNA levels in infected tissues (adult wing and leg primordia)
      via RNA interference (RNAi). The RNAi knock-down of BR-C resulted in the failure
      of animals to complete the larval-pupal transition or in later morphogenetic
      defects, including differentiation of adult compound eyes, legs, and wings from
      their larval progenitors. BR-C RNAi also perturbed the programmed cell death of
      larval silk glands. These developmental defects correspond to loss-of-function
      phenotypes of BR-C Drosophila mutants in both the morphogenetic and degenerative
      aspects, suggesting that the critical role of BR-C in metamorphosis is
      evolutionarily conserved. We also demonstrate that the Sindbis virus is a useful
      vehicle for silencing of developmental genes in new insect models.

PMID- 14668450
TI  - Evidence that transgenes encoding components of the Wnt signaling pathway
      preferentially induce mammary cancers from progenitor cells.
AB  - Breast cancer is a genetically and clinically heterogeneous disease, and the
      contributions of different target cells and different oncogenic mutations to this
      heterogeneity are not well understood. Here we report that mammary tumors induced
      by components of the Wnt signaling pathway contain heterogeneous cell types and
      express early developmental markers, in contrast to tumors induced by other
      signaling elements. Expression of the Wnt-1 protooncogene in mammary glands of
      transgenic mice expands a population of epithelial cells expressing progenitor
      cell markers, keratin 6 and Sca-1; subsequent tumors express these markers and
      contain luminal epithelial and myoepithelial tumor cells that share a secondary
      mutation, loss of Pten, implying that they arose from a common progenitor.
      Mammary tumors arising in transgenic mice expressing beta-catenin and c-Myc,
      downstream components of the canonical Wnt signaling pathway, also contain a
      significant proportion of myoepithelial cells and cells expressing keratin 6.
      Progenitor cell markers and myoepithelial cells, however, are lacking in mammary
      tumors from transgenic mice expressing Neu, H-Ras, or polyoma middle T antigen.
      These results suggest that mammary stem cells and/or progenitors to mammary
      luminal epithelial and myoepithelial cells may be the targets for oncogenesis by
      Wnt-1 signaling elements. Thus, the developmental heterogeneity of different
      breast cancers is in part a consequence of differential effects of oncogenes on
      distinct cell types in the breast.

PMID- 14668452
TI  - Unstable coronary-artery plaques.

PMID- 14668453
TI  - Chronic allograft nephropathy.

PMID- 14668454
TI  - Out of the shadows--MRI and the Nobel Prize.

PMID- 14668455
TI  - Comparison of sequential three-drug regimens as initial therapy for HIV-1
      infection.
AB  - BACKGROUND: The optimal sequencing of antiretroviral regimens for the treatment
      of infection with human immunodeficiency virus type 1 (HIV-1) is unknown. We
      compared several different antiretroviral treatment strategies. METHODS: This
      multicenter, randomized, partially double-blind trial used a factorial design to
      compare pairs of sequential three-drug regimens, starting with a regimen
      including zidovudine and lamivudine or a regimen including didanosine and
      stavudine in combination with either nelfinavir or efavirenz. The primary end
      point was the length of time to the failure of the second three-drug regimen.
      RESULTS: A total of 620 subjects who had not previously received antiretroviral
      therapy were followed for a median of 2.3 years. Starting with a three-drug
      regimen containing efavirenz combined with zidovudine and lamivudine (but not
      efavirenz combined with didanosine and stavudine) appeared to delay the failure
      of the second regimen, as compared with starting with a regimen containing
      nelfinavir (hazard ratio for failure of the second regimen, 0.71; 95 percent
      confidence interval, 0.48 to 1.06), as well as to delay the second virologic
      failure (hazard ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09), and
      significantly delayed the failure of the first regimen (hazard ratio, 0.39) and
      the first virologic failure (hazard ratio, 0.34). Starting with zidovudine and
      lamivudine combined with efavirenz (but not zidovudine and lamivudine combined
      with nelfinavir) appeared to delay the failure of the second regimen, as compared
      with starting with didanosine and stavudine (hazard ratio, 0.68), and
      significantly delayed both the first and the second virologic failures (hazard
      ratio for the first virologic failure, 0.39; hazard ratio for the second
      virologic failure, 0.47), as well as the failure of the first regimen (hazard
      ratio, 0.35). The initial use of zidovudine, lamivudine, and efavirenz resulted
      in a shorter time to viral suppression. CONCLUSIONS: The efficacy of
      antiretroviral drugs depends on how they are combined. The combination of
      zidovudine, lamivudine, and efavirenz is superior to the other antiretroviral
      regimens used as initial therapy in this study.

PMID- 14668456
TI  - Comparison of four-drug regimens and pairs of sequential three-drug regimens as
      initial therapy for HIV-1 infection.
AB  - BACKGROUND: It is unclear whether therapy for human immunodeficiency virus type 1
      (HIV-1) should be initiated with a four-drug or two sequential three-drug
      regimens. METHODS: In this multicenter trial we compared initial therapy
      involving four-drug regimens containing efavirenz and nelfinavir in combination
      with either didanosine and stavudine or zidovudine and lamivudine with therapy
      involving two consecutive three-drug regimens the first of which contained either
      efavirenz or nelfinavir. RESULTS: A total of 980 subjects were followed for a
      median of 2.3 years. There was no significant difference in the occurrence of
      regimen failures between the group that received the four-drug regimen containing
      didanosine, stavudine, nelfinavir, and efavirenz and the groups that received the
      three-drug regimens beginning with didanosine, stavudine, and nelfinavir (hazard
      ratio for regimen failure, 1.24) or didanosine, stavudine, and efavirenz (hazard
      ratio, 1.01). There was no significant difference between the group that received
      the four-drug regimen containing zidovudine, lamivudine, nelfinavir, and
      efavirenz and the groups that received the three-drug regimens beginning with
      zidovudine, lamivudine, and nelfinavir (hazard ratio, 1.06) or zidovudine,
      lamivudine, and efavirenz (hazard ratio, 1.45). A four-drug regimen was
      associated with a longer time to the first regimen failure than the three-drug
      regimens containing didanosine, stavudine, and nelfinavir (hazard ratio for a
      first regimen failure, 0.55); didanosine, stavudine, and efavirenz (hazard ratio,
      0.63); or zidovudine, lamivudine, and nelfinavir (hazard ratio, 0.49), but not
      the three-drug regimen containing zidovudine, lamivudine, and efavirenz (hazard
      ratio, 1.21). CONCLUSIONS: There was no significant difference in the duration of
      successful HIV-1 treatment between a single four-drug regimen and two consecutive
      three-drug regimens. Among these treatment strategies, initiating therapy with
      the three-drug regimen of zidovudine, lamivudine, and efavirenz is the optimal
      choice.

PMID- 14668457
TI  - Intraplaque hemorrhage and progression of coronary atheroma.
AB  - BACKGROUND: Intraplaque hemorrhage is common in advanced coronary atherosclerotic
      lesions. The relation between hemorrhage and the vulnerability of plaque to
      disruption may involve the accumulation of free cholesterol from erythrocyte
      membranes. METHODS: We stained multiple coronary lesions from 24 randomly
      selected patients who had died suddenly of coronary causes with an antibody
      against glycophorin A (a protein specific to erythrocytes that facilitates anion
      exchange) and Mallory's stain for iron (hemosiderin), markers of previous
      intraplaque hemorrhage. Coronary lesions were classified as lesions with
      pathologic intimal thickening, fibrous-cap atheromas with cores in an early or
      late stage of necrosis, or thin-cap fibrous atheromas (vulnerable plaques). The
      arterial response to plaque hemorrhage was further defined in a rabbit model of
      atherosclerosis. RESULTS: Only traces of glycophorin A and iron were found in
      lesions with pathologic intimal thickening or fibrous-cap atheromas with cores in
      an early stage of necrosis. In contrast, fibroatheromas with cores in a late
      stage of necrosis or thin caps had a marked increase in glycophorin A in regions
      of cholesterol clefts surrounded by iron deposits. Larger amounts of both
      glycophorin A and iron were associated with larger necrotic cores and greater
      macrophage infiltration. Rabbit lesions with induced intramural hemorrhage
      consistently showed cholesterol crystals with erythrocyte fragments, foam cells,
      and iron deposits. In contrast, control lesions from the same animals had a
      marked reduction in macrophages and lipid content. CONCLUSIONS: By contributing
      to the deposition of free cholesterol, macrophage infiltration, and enlargement
      of the necrotic core, the accumulation of erythrocyte membranes within an
      atherosclerotic plaque may represent a potent atherogenic stimulus. These factors
      may increase the risk of plaque destabilization.

PMID- 14668458
TI  - The natural history of chronic allograft nephropathy.
AB  - BACKGROUND: With improved immunosuppression and early allograft survival, chronic
      allograft nephropathy has become the dominant cause of kidney-transplant failure.
      METHODS: We evaluated the natural history of chronic allograft nephropathy in a
      prospective study of 120 recipients with type 1 diabetes, all but 1 of whom had
      received kidney-pancreas transplants. We obtained 961 kidney-transplant-biopsy
      specimens taken regularly from the time of transplantation to 10 years
      thereafter. RESULTS: Two distinctive phases of injury were evident as chronic
      allograft nephropathy evolved. An initial phase of early tubulointerstitial
      damage from ischemic injury (P<0.05), prior severe rejection (P<0.01), and
      subclinical rejection (P<0.01) predicted mild disease by one year, which was
      present in 94.2 percent of patients. Early subclinical rejection was common
      (affecting 45.7 percent of biopsy specimens at three months), and the risk was
      increased by the occurrence of a prior episode of severe rejection and reduced by
      tacrolimus and mycophenolate therapy (both P<0.05) and gradually abated after one
      year. Both subclinical rejection and chronic rejection were associated with
      increased tubulointerstitial damage (P<0.01). Beyond one year, a later phase of
      chronic allograft nephropathy was characterized by microvascular and glomerular
      injury. Chronic rejection (defined as persistent subclinical rejection for two
      years or longer) was uncommon (5.8 percent). Progressive high-grade arteriolar
      hyalinosis with luminal narrowing, increasing glomerulosclerosis, and additional
      tubulointerstitial damage was accompanied by the use of calcineurin inhibitors.
      Nephrotoxicity, implicated in late ongoing injury, was almost universal at 10
      years, even in grafts with excellent early histologic findings. By 10 years,
      severe chronic allograft nephropathy was present in 58.4 percent of patients,
      with sclerosis in 37.3 percent of glomeruli. Tubulointerstitial and glomerular
      damage, once established, was irreversible, resulting in declining renal function
      and graft failure. CONCLUSIONS: Chronic allograft nephropathy represents
      cumulative and incremental damage to nephrons from time-dependent immunologic and
      nonimmunologic causes.

PMID- 14668459
TI  - Use of an anti-interleukin-5 antibody in the hypereosinophilic syndrome with
      eosinophilic dermatitis.

PMID- 14668460
TI  - Images in clinical medicine. Cecal Kaposi's sarcoma.

PMID- 14668461
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 38-2003. A 12-year-old girl with fever and coma.

PMID- 14668462
TI  - HIV therapy--what do we know, and when do we know it?

PMID- 14668463
TI  - The meningococcal vaccine--public policy and individual choices.

PMID- 14668464
TI  - Hepatic diseases--hitting the target with inhibitory RNAs.

PMID- 14668465
TI  - Oral anticoagulation and stroke in atrial fibrillation.

PMID- 14668466
TI  - HIV infection masquerading as monoclonal gammopathy of unknown significance.

PMID- 14668467
TI  - Oxygen-saturation targets in extremely preterm infants.

PMID- 14668468
TI  - Bulimia nervosa.

PMID- 14668469
TI  - Molecular epidemiology of tuberculosis.

PMID- 14668470
TI  - Inhibition of food intake by peptide YY3-36.

PMID- 14668471
TI  - Mechanisms of drug addiction.

PMID- 14668472
TI  - False positive test for aspergillus antigenemia related to concomitant
      administration of piperacillin and tazobactam.

PMID- 14668473
TI  - Keratoderma blennorrhagicum.

PMID- 14668474
TI  - Images in clinical medicine. Peripheral embolism from an aortic-arch atheroma.

PMID- 14668475
TI  - EFA6, exchange factor for ARF6, regulates the actin cytoskeleton and associated
      tight junction in response to E-cadherin engagement.
AB  - We addressed the role of EFA6, exchange factor for ARF6, during the development
      of epithelial cell polarity in Madin-Darby canine kidney cells. EFA6 is located
      primarily at the apical pole of polarized cells, including the plasma membrane.
      After calcium-triggered E-cadherin-mediated cell adhesion, EFA6 is recruited to a
      Triton X-100-insoluble fraction and its protein level is increased concomitantly
      to the accelerated formation of a functional tight junction (TJ). The expression
      of EFA6 results in the selective retention at the cell surface of the TJ protein
      occludin. This effect is due to EFA6 capacities to promote selectively the
      stability of the apical actin ring onto which the TJ is anchored, resulting in
      the exclusion of TJ proteins from endocytosis. Finally, our data suggest that
      EFA6 effects are achieved by the coordinate action of both its exchange activity
      and its actin remodeling C-terminal domain. We conclude that EFA6 is a signaling
      molecule that responds to E-cadherin engagement and is involved in TJ formation
      and stability.

PMID- 14668476
TI  - The role of heat shock transcription factor 1 in the genome-wide regulation of
      the mammalian heat shock response.
AB  - Previous work has implicated heat shock transcription factor 1 (HSF1) as the
      primary transcription factor responsible for the transcriptional response to heat
      stress in mammalian cells. We characterized the heat shock response of mammalian
      cells by measuring changes in transcript levels and assaying binding of HSF1 to
      promoter regions for candidate heat shock genes chosen by a combination of genome
      wide computational and experimental methods. We found that many heat-inducible
      genes have HSF1 binding sites (heat shock elements, HSEs) in their promoters that
      are bound by HSF1. Surprisingly, for 24 heat-inducible genes, we detected no HSEs
      and no HSF1 binding. Furthermore, of 182 promoters with likely HSE sequences, we
      detected HSF1 binding at only 94 of these promoters. Also unexpectedly, we found
      48 genes with HSEs in their promoters that are bound by HSF1 but that
      nevertheless did not show induction after heat shock in the cell types we
      examined. We also studied the transcriptional response to heat shock in
      fibroblasts from mice lacking the HSF1 gene. We found 36 genes in these cells
      that are induced by heat as well as they are in wild-type cells. These results
      provide evidence that HSF1 does not regulate the induction of every transcript
      that accumulates after heat shock, and our results suggest that an independent
      posttranscriptional mechanism regulates the accumulation of a significant number
      of transcripts.

PMID- 14668477
TI  - Role of binding of plectin to the integrin beta4 subunit in the assembly of
      hemidesmosomes.
AB  - We have previously shown that plectin is recruited into hemidesmosomes through
      association of its actin-binding domain (ABD) with the first pair of fibronectin
      type III (FNIII) repeats and a small part of the connecting segment (residues
      1328-1355) of the integrin beta4 subunit. Here, we show that two proline residues
      (P1330 and P1333) in this region of the connecting segment are critical for
      supporting beta4-mediated recruitment of plectin. Additional binding sites for
      the plakin domain of plectin on beta4 were identified in biochemical and yeast
      two-hybrid assays. These sites are located at the end of the connecting segment
      (residues 1383-1436) and in the region containing the fourth FNIII repeat and the
      C-tail (residues 1570-1752). However, in cells, these additional binding sites
      cannot induce the assembly of hemidesmosomes without the interaction of the
      plectin-ABD with beta4. Because the additional plectin binding sites overlap with
      sequences that mediate an intramolecular association of the beta4 cytoplasmic
      domain, we propose that they are not accessible for binding and need to become
      exposed as the result of the binding of the plectin-ABD to beta4. Furthermore,
      these additional binding sites might be necessary to position the beta4
      cytoplasmic domain for an optimal interaction with other hemidesmosomal
      components, thereby increasing the efficiency of hemidesmosome assembly.

PMID- 14668478
TI  - Epidermolysis bullosa simplex-type mutations alter the dynamics of the keratin
      cytoskeleton and reveal a contribution of actin to the transport of keratin
      subunits.
AB  - Dominant keratin mutations cause epidermolysis bullosa simplex by transforming
      keratin (K) filaments into aggregates. As a first step toward understanding the
      properties of mutant keratins in vivo, we stably transfected epithelial cells
      with an enhanced yellow fluorescent protein-tagged K14R125C mutant. K14R125C
      became localized as aggregates in the cell periphery and incorporated into
      perinuclear keratin filaments. Unexpectedly, keratin aggregates were in dynamic
      equilibrium with soluble subunits at a half-life time of <15 min, whereas
      filaments were extremely static. Therefore, this dominant-negative mutation acts
      by altering cytoskeletal dynamics and solubility. Unlike previously postulated,
      the dominance of mutations is limited and strictly depends on the ratio of mutant
      to wild-type protein. In support, K14R125C-specific RNA interference experiments
      resulted in a rapid disintegration of aggregates and restored normal filaments.
      Most importantly, live cell inhibitor studies revealed that the granules are
      transported from the cell periphery inwards in an actin-, but not microtubule
      based manner. The peripheral granule zone may define a region in which keratin
      precursors are incorporated into existing filaments. Collectively, our data have
      uncovered the transient nature of keratin aggregates in cells and offer a
      rationale for the treatment of epidermolysis bullosa simplex by using short
      interfering RNAs.

PMID- 14668479
TI  - The yeast casein kinase Yck3p is palmitoylated, then sorted to the vacuolar
      membrane with AP-3-dependent recognition of a YXXPhi adaptin sorting signal.
AB  - Our previous work found the two yeast plasma membrane-localized casein kinases
      Yck1p and Yck2p to be palmitoylated on C-terminal Cys-Cys sequences by the
      palmitoyl transferase Akr1p. The present work examines a third casein kinase,
      Yck3p, which ends with the C-terminal sequence Cys-Cys-Cys-Cys-Phe-Cys-Cys-Cys.
      Yck3p is palmitoylated and localized to the vacuolar membrane. While the C
      terminal cysteines are required for this palmitoylation, Akr1p is not.
      Palmitoylation requires the C-terminal Yck3p residues 463-524, whereas
      information for vacuolar sorting maps to the 409-462 interval. Vacuolar sorting
      is disrupted in cis through deletion of the 409-462 sequences and in trans
      through mutation of the AP-3 adaptin complex; both cis- and trans-mutations
      result in Yck3p missorting to the plasma membrane. This missorted Yck3p restores
      37 degrees C viability to yck1Delta yck2-ts cells. yck1Delta yck2-ts suppressor
      mutations isolated within the YCK3 gene identify the Yck3p vacuolar sorting
      signal-the tetrapeptide YDSI, a perfect fit to the YXXPhi adaptin-binding
      consensus. Although YXXPhi signals have a well-appreciated role in the adaptin
      mediated sorting of mammalian cells, this is the first signal of this class to be
      identified in yeast.

PMID- 14668480
TI  - Phagocytosis of necrotic cells by macrophages is phosphatidylserine dependent and
      does not induce inflammatory cytokine production.
AB  - Apoptotic cells are cleared by phagocytosis during development, homeostasis, and
      pathology. However, it is still unclear how necrotic cells are removed. We
      compared the phagocytic uptake by macrophages of variants of L929sA murine
      fibrosarcoma cells induced to die by tumor necrosis factor-induced necrosis or by
      Fas-mediated apoptosis. We show that apoptotic and necrotic cells are recognized
      and phagocytosed by macrophages, whereas living cells are not. In both cases,
      phagocytosis occurred through a phosphatidylserine-dependent mechanism,
      suggesting that externalization of phosphatidylserine is a general trigger for
      clearance by macrophages. However, uptake of apoptotic cells was more efficient
      both quantitatively and kinetically than phagocytosis of necrotic cells. Electron
      microscopy showed clear morphological differences in the mechanisms used by
      macrophages to engulf necrotic and apoptotic cells. Apoptotic cells were taken up
      as condensed membrane-bound particles of various sizes rather than as whole
      cells, whereas necrotic cells were internalized only as small cellular particles
      after loss of membrane integrity. Uptake of neither apoptotic nor necrotic L929
      cells by macrophages modulated the expression of proinflammatory cytokines by the
      phagocytes.

PMID- 14668481
TI  - Transcriptional remodeling in response to iron deprivation in Saccharomyces
      cerevisiae.
AB  - The budding yeast Saccharomyces cerevisiae responds to depletion of iron in the
      environment by activating Aft1p, the major iron-dependent transcription factor,
      and by transcribing systems involved in the uptake of iron. Here, we have studied
      the transcriptional response to iron deprivation and have identified new Aft1p
      target genes. We find that other metabolic pathways are regulated by iron: biotin
      uptake and biosynthesis, nitrogen assimilation, and purine biosynthesis. Two
      enzymes active in these pathways, biotin synthase and glutamate synthase, require
      an iron-sulfur cluster for activity. Iron deprivation activates transcription of
      the biotin importer and simultaneously represses transcription of the entire
      biotin biosynthetic pathway. Multiple genes involved in nitrogen assimilation and
      amino acid metabolism are induced by iron deprivation, whereas glutamate
      synthase, a key enzyme in nitrogen assimilation, is repressed. A CGG palindrome
      within the promoter of glutamate synthase confers iron-regulated expression,
      suggesting control by a transcription factor of the binuclear zinc cluster
      family. We provide evidence that yeast subjected to iron deprivation undergo a
      transcriptional remodeling, resulting in a shift from iron-dependent to parallel,
      but iron-independent, metabolic pathways.

PMID- 14668482
TI  - Phosphorylation of high-mobility group protein A2 by Nek2 kinase during the first
      meiotic division in mouse spermatocytes.
AB  - The mitogen-activated protein kinase (MAPK) pathway is required for maintaining
      the chromatin condensed during the two meiotic divisions and to avoid a second
      round of DNA duplication. However, molecular targets of the MAPK pathway on
      chromatin have not yet been identified. Here, we show that the architectural
      chromatin protein HMGA2 is highly expressed in male meiotic cells. Furthermore,
      Nek2, a serine-threonine kinase activated by the MAPK pathway in mouse pachytene
      spermatocytes, directly interacts with HMGA2 in vitro and in mouse spermatocytes.
      The interaction does not depend on the activity of Nek2 and seems constitutive.
      On progression from pachytene to metaphase, Nek2 is activated and HMGA2 is
      phosphorylated in an MAPK-dependent manner. We also show that Nek2 phosphorylates
      in vitro HMGA2 and that this phosphorylation decreases the affinity of HMGA2 for
      DNA and might favor its release from the chromatin. Indeed, we find that most
      HMGA2 associates with chromatin in mouse pachytene spermatocytes, whereas it is
      excluded from the chromatin upon the G2/M progression. Because hmga2-/- mice are
      sterile and show a dramatic impairment of spermatogenesis, it is possible that
      the functional interaction between HMGA2 and Nek2 plays a crucial role in the
      correct process of chromatin condensation in meiosis.

PMID- 14668483
TI  - Sec61p contributes to signal sequence orientation according to the positive
      inside rule.
AB  - Protein targeting to the endoplasmic reticulum is mediated by signal or signal
      anchor sequences. They also play an important role in protein topogenesis,
      because their orientation in the translocon determines whether their N- or C
      terminal sequence is translocated. Signal orientation is primarily determined by
      charged residues flanking the hydrophobic core, whereby the more positive end is
      predominantly positioned to the cytoplasmic side of the membrane, a phenomenon
      known as the "positive-inside rule." We tested the role of conserved charged
      residues of Sec61p, the major component of the translocon in Saccharomyces
      cerevisiae, in orienting signals according to their flanking charges by site
      directed mutagenesis by using diagnostic model proteins. Mutation of R67, R74, or
      E382 in Sec61p reduced C-terminal translocation of a signal-anchor protein with a
      positive N-terminal flanking sequence and increased it for signal-anchor proteins
      with positive C-terminal sequences. These mutations produced a stronger effect on
      substrates with greater charge difference across the hydrophobic core of the
      signal. For some of the substrates, a charge mutation in Sec61p had a similar
      effect as one in the substrate polypeptides. Although these three residues do not
      account for the entire charge effect in signal orientation, the results show that
      Sec61p contributes to the positive-inside rule.

PMID- 14668484
TI  - Global gene expression responses of fission yeast to ionizing radiation.
AB  - A coordinated transcriptional response to DNA-damaging agents is required to
      maintain genome stability. We have examined the global gene expression responses
      of the fission yeast Schizosaccharomyces pombe to ionizing radiation (IR) by
      using DNA microarrays. We identified approximately 200 genes whose transcript
      levels were significantly altered at least twofold in response to 500 Gy of gamma
      IR in a temporally defined manner. The majority of induced genes were core
      environmental stress response genes, whereas the remaining genes define a
      transcriptional response to DNA damage in fission yeast. Surprisingly, few DNA
      repair and checkpoint genes were transcriptionally modulated in response to IR.
      We define a role for the stress-activated mitogen-activated protein kinase
      Sty1/Spc1 and the DNA damage checkpoint kinase Rad3 in regulating core
      environmental stress response genes and IR-specific response genes, both
      independently and in concert. These findings suggest a complex network of
      regulatory pathways coordinate gene expression responses to IR in eukaryotes.

PMID- 14668485
TI  - A striking quality control subcompartment in Saccharomyces cerevisiae: the
      endoplasmic reticulum-associated compartment.
AB  - The folding of nascent secretory and membrane proteins is monitored by the
      endoplasmic reticulum (ER) quality control system. Misfolded proteins are
      retained in the ER and can be removed by ER-associated degradation. As a model
      for the ER quality control of multispanning membrane proteins in yeast, we have
      been studying mutant forms of Ste6p. Here, we identify mislocalized mutant forms
      of Ste6p that induce the formation of, and localize to, prominent structures that
      are absent in normal cells. We have named these structures ER-associated
      compartments (ERACs), based on their juxtaposition to and connection with the ER,
      as observed by fluorescence and electron microscopy. ERACs comprise a network of
      tubulo-vesicular structures that seem to represent proliferated ER membranes.
      Resident ER lumenal and membrane proteins are present in ERACs in addition to
      their normal ER localization, suggesting there is no barrier for their entry into
      ERACs. However, the forms of Ste6p in ERACs are excluded from the ER and do not
      enter the secretory pathway; instead, they are ultimately targeted for ER
      associated degradation. The presence of ERACs does not adversely affect secretory
      protein traffic through the ER and does not lead to induction of the unfolded
      protein response. We propose that ERACs may be holding sites to which misfolded
      membrane proteins are specifically diverted so as not to interfere with normal
      cellular functions. We discuss the likelihood that related ER membrane
      proliferations that form in response to certain other mutant or unassembled
      membrane proteins may be substantially similar to ERACs.

PMID- 14668486
TI  - Regulation of longevity in Caenorhabditis elegans by heat shock factor and
      molecular chaperones.
AB  - The correlation between longevity and stress resistance observed in long-lived
      mutant animals suggests that the ability to sense and respond to environmental
      challenges could be important for the regulation of life span. We therefore
      examined the role of heat shock factor (HSF-1), a master transcriptional
      regulator of stress-inducible gene expression and protein folding homeostasis, in
      the regulation of longevity. Down-regulation of hsf-1 by RNA interference
      suppressed longevity of mutants in an insulin-like signaling (ILS) pathway that
      functions in the nervous system of Caenorhabditis elegans to influence aging. hsf
      1 was also required for temperature-induced dauer larvae formation in an ILS
      mutant. Using tissue-specific expression of wild-type or dominant negative HSF-1,
      we demonstrated that HSF-1 acts in multiple tissues to regulate longevity. Down
      regulation of individual molecular chaperones, transcriptional targets of HSF-1,
      also decreased longevity of long-lived mutant but not wild-type animals. However,
      suppression by individual chaperones was to a lesser extent, suggesting an
      important role for networks of chaperones. The interaction of ILS with HSF-1
      could represent an important molecular strategy to couple the regulation of
      longevity with an ancient genetic switch that governs the ability of cells to
      sense and respond to stress.

PMID- 14668487
TI  - Novel kelch-like protein, KLEIP, is involved in actin assembly at cell-cell
      contact sites of Madin-Darby canine kidney cells.
AB  - Dynamic rearrangements of cell-cell adhesion underlie a diverse range of
      physiological processes, but their precise molecular mechanisms are still
      obscure. Thus, identification of novel players that are involved in cell-cell
      adhesion would be important. We isolated a human kelch-related protein, Kelch
      like ECT2 interacting protein (KLEIP), which contains the broad-complex,
      tramtrack, bric-a-brac (BTB)/poxvirus, zinc finger (POZ) motif and six-tandem
      kelch repeats. KLEIP interacted with F-actin and was concentrated at cell-cell
      contact sites of Madin-Darby canine kidney cells, where it colocalized with F
      actin. Interestingly, this localization took place transiently during the
      induction of cell-cell contact and was not seen at mature junctions. KLEIP
      recruitment and actin assembly were induced around E-cadherin-coated beads placed
      on cell surfaces. The actin depolymerizing agent cytochalasin B inhibited this
      KLEIP recruitment around E-cadherin-coated beads. Moreover, constitutively active
      Rac1 enhanced the recruitment of KLEIP as well as F-actin to the adhesion sites.
      These observations strongly suggest that KLEIP is localized on actin filaments at
      the contact sites. We also found that N-terminal half of KLEIP, which lacks the
      actin-binding site and contains the sufficient sequence for the localization at
      the cell-cell contact sites, inhibited constitutively active Rac1-induced actin
      assembly at the contact sites. We propose that KLEIP is involved in Rac1-induced
      actin organization during cell-cell contact in Madin-Darby canine kidney cells.

PMID- 14668488
TI  - A unique region of RILP distinguishes it from its related proteins in its
      regulation of lysosomal morphology and interaction with Rab7 and Rab34.
AB  - Rab7 and Rab34 are implicated in regulation of lysosomal morphology and they
      share a common effector referred to as the RILP (Rab-interacting lysosomal
      protein). Two novel proteins related to RILP were identified and are tentatively
      referred to as RLP1 and RLP2 (for RILP-like protein 1 and 2, respectively).
      Overexpression of RILP caused enlarged lysosomes that are positioned more
      centrally in the cell. However, the morphology and distribution of lysosomes were
      not affected by overexpression of either RLP1 or RLP2. The molecular basis for
      the effect of RILP on lysosomes was investigated, leading to the demonstration
      that a 62-residue region (amino acids 272-333) of RILP is necessary for RILP's
      role in regulating lysosomal morphology. Remarkably, transferring this 62-residue
      region unique to RILP into corresponding sites in RLP1 rendered the chimeric
      protein capable of regulating lysosome morphology. A correlation between the
      interaction with GTP-bound form of both Rab proteins and the capability of
      regulating lysosomes was established. These results define a unique region in
      RILP responsible for its specific role in regulating lysosomal morphology as well
      as in its interaction with Rab7 and Rab34.

PMID- 14668489
TI  - gamma-tubulin plays an essential role in the coordination of mitotic events.
AB  - Recent data from multiple organisms indicate that gamma-tubulin has essential,
      but incompletely defined, functions in addition to nucleating microtubule
      assembly. To investigate these functions, we examined the phenotype of mipAD159,
      a cold-sensitive allele of the gamma-tubulin gene of Aspergillus nidulans.
      Immunofluorescence microscopy of synchronized material revealed that at a
      restrictive temperature mipAD159 does not inhibit mitotic spindle formation.
      Anaphase A was inhibited in many nuclei, however, and after a slight delay in
      mitosis (approximately 6% of the cell cycle period), most nuclei reentered
      interphase without dividing. In vivo observations of chromosomes at a restrictive
      temperature revealed that mipAD159 caused a failure of the coordination of late
      mitotic events (anaphase A, anaphase B, and chromosomal disjunction) and nuclei
      reentered interphase quickly even though mitosis was not completed successfully.
      Time-lapse microscopy also revealed that transient mitotic spindle abnormalities,
      in particular bent spindles, were more prevalent in mipAD159 strains than in
      controls. In experiments in which microtubules were depolymerized with benomyl,
      mipAD159 nuclei exited mitosis significantly more quickly (as judged by
      chromosomal condensation) than nuclei in a control strain. These data reveal that
      gamma-tubulin has an essential role in the coordination of late mitotic events,
      and a microtubule-independent function in mitotic checkpoint control.

PMID- 14668491
TI  - Rac GTPase instructs nuclear factor-kappaB activation by conveying the SCF
      complex and IkBalpha to the ruffling membranes.
AB  - Nuclear factor-kappaB (NF-kappaB) is a ubiquitously expressed transcription
      factor that plays a central role in directing a vast range of cellular functions.
      Its activation is controlled by the Rac GTPase and relies on the coordinated
      cooperation of the E3-ligase complex SCF(betaTrCP), composed by Skp-1/Cullin-1,
      Rbx/Roc1, and the beta-TrCP proteins. Recently, Cullin-1 has been reported to
      form a complex with the activated Rac GTPase. Here, we show that the specific
      activation of the Rac GTPase, besides directing its own positioning, induces the
      relocalization of the SCF component Cullin-1 to the ruffling membranes. This
      occurred only if the ruffles were stimulated by the Rac GTPase and was
      accompanied by the repositioning to the same intracellular compartment of the SCF
      protein Skp-1 and the ubiquitin-like molecule Nedd-8. The SCF substrate IkBalpha
      was also directed to the ruffling membranes in a Rac-dependent way. The novelty
      of these findings is in respect to the demonstration that the correct positioning
      at the ruffling membranes is crucial for the subsequent series of events that
      leads to IkBalpha proteasomal degradation and the resultant activation of NF
      kappaB. Consequently, this points to the role of Rac as a docking molecule in NF
      kappaB activation.

PMID- 14668490
TI  - Mammalian late vacuole protein sorting orthologues participate in early endosomal
      fusion and interact with the cytoskeleton.
AB  - In Saccharomyces cerevisiae, the class C vacuole protein sorting (Vps) proteins,
      together with Vam2p/Vps41p and Vam6p/Vps39p, form a complex that interacts with
      soluble N-ethylmaleimide-sensitive factor attachment protein receptor and Rab
      proteins to "tether" vacuolar membranes before fusion. To determine a role for
      the corresponding mammalian orthologues, we examined the function, localization,
      and protein interactions of endogenous mVps11, mVps16, mVps18, mVam2p, and mVam6.
      We found a significant proportion of these proteins localized to early endosome
      antigen-1 and transferrin receptor-positive early endosomes in Vero, normal rat
      kidney, and Chinese hamster ovary cells. Immunoprecipitation experiments showed
      that mVps18 not only interacted with Syntaxin (Syn)7, vesicle-associated membrane
      protein 8, and Vti1-b but also with Syn13, Syn6, and the Sec1/Munc18 protein
      mVps45, which catalyze early endosomal fusion events. Moreover, anti-mVps18
      antibodies inhibited early endosome fusion in vitro. Mammalian mVps18 also
      associated with mVam2 and mVam6 as well as with the microtubule-associated Hook1
      protein, an orthologue of the Drosophila Hook protein involved in endosome
      biogenesis. Using in vitro binding and immunofluorescence experiments, we found
      that mVam2 and mVam6 also associated with microtubules, whereas mVps18, mVps16,
      and mVps11 associated with actin filaments. These data indicate that the late Vps
      proteins function during multiple soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor-mediated fusion events throughout the endocytic
      pathway and that their activity may be coordinated with cytoskeletal function.

PMID- 14668492
TI  - Reconstituted TOM core complex and Tim9/Tim10 complex of mitochondria are
      sufficient for translocation of the ADP/ATP carrier across membranes.
AB  - Precursor proteins of the solute carrier family and of channel forming Tim
      components are imported into mitochondria in two main steps. First, they are
      translocated through the TOM complex in the outer membrane, a process assisted by
      the Tim9/Tim10 complex. They are passed on to the TIM22 complex, which
      facilitates their insertion into the inner membrane. In the present study, we
      have analyzed the function of the Tim9/Tim10 complex in the translocation of
      substrates across the outer membrane of mitochondria. The purified TOM core
      complex was reconstituted into lipid vesicles in which purified Tim9/Tim10
      complex was entrapped. The precursor of the ADP/ATP carrier (AAC) was found to be
      translocated across the membrane of such lipid vesicles. Thus, these components
      are sufficient for translocation of AAC precursor across the outer membrane.
      Peptide libraries covering various substrate proteins were used to identify
      segments that are bound by Tim9/Tim10 complex upon translocation through the TOM
      complex. The patterns of binding sites on the substrate proteins suggest a
      mechanism by which portions of membrane-spanning segments together with flanking
      hydrophilic segments are recognized and bound by the Tim9/Tim10 complex as they
      emerge from the TOM complex into the intermembrane space.

PMID- 14668494
TI  - Open fractures of the calcaneus: soft-tissue injury determines outcome.
AB  - BACKGROUND: Studies of open calcaneal fractures have been limited and have not
      analyzed results according to wound location, severity of soft-tissue disruption,
      fracture type, or treatment method. In this study, results were evaluated on the
      basis of the hypothesis that early surgical intervention was indicated. METHODS:
      Between 1989 and 1997, 503 calcaneal fractures were treated at our institution,
      and forty-three of these fractures, in forty-two patients, were open (8.5%).
      According to the Gustilo classification there were nine type-I, eight type-II,
      twelve type-IIIA, and thirteen type-IIIB open fractures as well as one type-IIIC
      open fracture. All fractures were treated according to the same protocol,
      consisting of intravenous administration of antibiotics chosen on the basis of
      the wound type, irrigation and debridement in the operating room, temporary wound
      coverage, and initial stabilization of the limb. Definitive final fixation was
      performed after the wound was clean, and soft-tissue swelling was minimal. The
      final follow-up examinations were performed at a minimum of two years after
      treatment. Clinical results were graded with use of the AOFAS (American
      Orthopaedic Foot and Ankle Society) score. RESULTS: An infection developed at the
      sites of 37% of the forty-three fractures, with osteomyelitis developing at the
      sites of 19%. Seven of the nine type-I open fractures were treated with open
      reduction and internal fixation or with primary fusion, with no major
      complications and a good-to-excellent short-term result. Three of the eight type
      II open fractures were complicated by an infection. Three of the twelve type-IIIA
      open fractures and ten of the thirteen type-IIIB open fractures were complicated
      by an infection. Six of the infections associated with a type-IIIB open fracture
      progressed to osteomyelitis, and three of those cases led to an amputation.
      Overall, thirteen (50%) of the twenty-six type-III open fractures were
      complicated by an infection, with osteomyelitis occurring in seven (27%). Thirty
      three patients with a total of thirty-four open calcaneal fractures were
      available for follow-up at a minimum of two years, and an average of fifty-five
      months. The average AOFAS hindfoot score for the twenty-seven patients who had
      not undergone amputation was 71 points. CONCLUSIONS: Open calcaneal fractures
      have a high propensity for deep infection despite the use of an aggressive
      treatment protocol to prevent it. It appears that type-I and type-II open
      fractures associated with a medial wound can be treated with open reduction and
      internal fixation. Type-II fractures associated with a wound in another location
      should be treated with limited or no internal fixation. Type-III open fractures,
      and especially type-IIIB open fractures, require extensive debridement and prompt
      soft-tissue coverage as soon as possible. Early internal fixation should be
      avoided in this subgroup because of the high rates of osteomyelitis and
      subsequent amputation.

PMID- 14668495
TI  - Thermal capsular shrinkage for treatment of multidirectional instability of the
      shoulder.
AB  - BACKGROUND: Capsular laxity is the main pathology in patients with
      multidirectional instability, and thermal shrinkage has been commonly employed to
      treat this condition. The objective of this study was to evaluate thermal
      capsular shrinkage as a treatment of multidirectional instability of the
      shoulder. METHODS: Nineteen consecutive patients with multidirectional
      instability were treated with thermal shrinkage. Fifteen patients had involuntary
      instability, and four had voluntary instability. The predominant direction of the
      instability was anteroinferior in ten patients and posterior in five; four
      patients had instability in multiple directions. Patients were followed for a
      minimum of two years or until surgical failure and recurrence of symptoms.
      Postoperatively, the patients wore a sling for three weeks, and they were
      evaluated regularly at three, six, and twelve months. The Western Ontario
      Shoulder Instability Index as well as subjective and objective evaluations of the
      patient's function, range of motion, pain, and instability were used as clinical
      outcome measures. RESULTS: Nine patients had recurrence of the instability at an
      average of nine months (range, seven to fourteen months) following the surgical
      procedure. Four patients had sensory dysesthesias in the axillary nerve
      distribution, and one of them had deltoid weakness. All neurological symptoms
      resolved within nine months. The surgical procedure failed in the five patients
      with predominantly posterior instability. It failed in only two of the ten
      patients with predominantly anteroinferior instability, and overall this group
      had objective improvement. CONCLUSIONS: Thermal capsular shrinkage used to treat
      multidirectional instability had a substantial failure rate with associated
      postoperative complications, including recurrence of instability (nine of the
      nineteen patients), stiffness (five patients), and neurological symptoms (four
      patients).

PMID- 14668496
TI  - Fate of cementless acetabular components retained during revision total hip
      arthroplasty.
AB  - BACKGROUND: Removal of a well-fixed cementless acetabular component can result in
      increased operative time and postoperative morbidity. The objectives of this
      retrospective study were to determine whether retention of a well-fixed
      acetabular component at the time of isolated femoral revision was compatible with
      long-term socket survival. METHODS: The records of eighty-three consecutive
      patients (ninety hips) in whom a well-fixed cementless socket had been retained
      during revision of a femoral component were reviewed. The mean age of the
      patients was 48.7 years at the time of the primary arthroplasty and 54.1 years at
      the time of femoral revision. The radiographic analysis was based on
      anteroposterior radiographs and was performed by a single independent reviewer.
      The intraoperative criterion for stability of the socket was the absence of
      movement at the bone-implant interface during the application of direct pressure
      to the edges of the socket in four quadrants with use of a metallic pusher.
      RESULTS: At the time of the isolated femoral revision, no socket demonstrated a
      radiolucent line measuring >1 mm in any two zones and forty of the ninety hips
      had periacetabular osteolysis. The mean size of the osteolytic lesions was 5.71
      cm(2) (range, 0.4 to 24.2 cm(2)), and twenty-eight of the forty hips underwent
      bone-grafting. The mean duration of follow-up was 9.7 years after the isolated
      femoral revision and 14.9 years after the primary arthroplasty. Five acetabular
      sockets were revised at a mean of 6.8 years after the femoral revision. Only one
      of these sockets had failed because of aseptic loosening. With revision of the
      acetabular component for any reason as the end point, the survival rate was 98.7%
      at five years and 93.5% at ten years after the femoral revision and 100% at ten
      years and 93.9% at fifteen years after the primary arthroplasty. No hip showed
      recurrence or expansion of periacetabular osteolysis. The prevalence of
      dislocation was 16% (fourteen of ninety). CONCLUSIONS: Revision of a stable,
      cementless acetabular component solely on the basis of its duration in vivo or
      the presence of periacetabular osteolysis does not appear to be warranted.
      Retention of the socket with grafting of larger periacetabular osteolytic lesions
      appears to be consistent with satisfactory socket longevity.

PMID- 14668497
TI  - Older women with fractures: patients falling through the cracks of guideline
      recommended osteoporosis screening and treatment.
AB  - BACKGROUND: Many older patients with fractures are not managed in accordance with
      evidence-based clinical guidelines for osteoporosis. Guidelines recommend that
      these patients receive treatment for clinically apparent osteoporosis or have
      bone mineral density measurements followed by treatment when appropriate. This
      cohort study was conducted to further characterize the gap between guidelines and
      actual practice with regard to bone mineral density measurement and treatment of
      older women after a fracture. Our purpose was to aid in the design of more
      effective future interventions. METHODS: We identified female members of a not
      for-profit group-model health maintenance organization who were fifty years of
      age or older and who had a diagnosis of a new fracture as defined in the study.
      We used administrative databases and the clinical electronic medical records to
      obtain data on demographics, diagnoses, drugs dispensed by the pharmacy, and the
      measurement of bone mineral density. RESULTS: The study population included 3812
      women with an average age of 71.3 years. Fewer than 12% of the women had a
      diagnosis of osteoporosis prior to the index fracture; 10.7% had an increased
      risk for secondary osteoporosis and 38.8%, for falls because of a diagnosis or
      medication. It was found that 46.4% of the study population had been managed as
      specified by clinical guidelines. The patients who had been managed as specified
      by the guidelines were younger and less likely to have the risk factor of a
      weight of <127 lb (58 kg), a hip fracture, or a wrist fracture. They were also
      more likely to be taking steroids on a chronic basis and to have had a vertebral
      fracture. The percentage of women who had measurement of bone mineral density
      increased during the study period, from 1.3% in 1998 to 10.2% in 2001. Of the
      patients receiving treatment for osteoporosis, 73.6% adhered to the treatment
      regimen. CONCLUSIONS: Adherence to guidelines for evaluation and treatment for
      osteoporosis after a patient sustained a fracture did not improve between 1998
      and 2001 despite the promulgation of evidence-based guidelines. Methods to
      enhance education and facilitate processes of care will be necessary to reduce
      this gap. It may be fruitful to target high-risk subgroups for tailored
      interventions for prevention of refracture.

PMID- 14668498
TI  - Harrington and Cotrel-Dubousset instrumentation in adolescent idiopathic
      scoliosis. Long-term functional and radiographic outcomes.
AB  - BACKGROUND: Previous studies have shown that the long-term clinical outcome does
      not correlate with the radiographic outcome in patients treated with Harrington
      instrumentation for adolescent idiopathic scoliosis. Cotrel-Dubousset
      instrumentation has been reported to provide better correction radiographically,
      but it is unclear whether it provides better long-term clinical or functional
      outcomes. We are not aware of any long-term studies comparing Harrington and
      Cotrel-Dubousset instrumentation. METHODS: Seventy-eight patients in whom
      adolescent idiopathic scoliosis was treated with Harrington instrumentation and
      fifty-seven in whom it was treated with Cotrel-Dubousset instrumentation
      participated in this study. The mean duration of follow-up was 20.8 years for the
      Harrington instrumentation group and 13.0 years for the Cotrel-Dubousset
      instrumentation group. The mean age at the time of follow-up was thirty-six years
      and twenty-eight years, respectively. Radiographs were made preoperatively and at
      the two-year and final follow-up examinations. The Scoliosis Research Society
      questionnaire was completed, a physical examination was performed, and spinal
      mobility and non-dynamometric trunk strength were measured at the final follow-up
      visit. RESULTS: The mean preoperative Cobb angle of the thoracic curves was 53
      degrees in the Harrington instrumentation group and 55 degrees in the Cotrel
      Dubousset instrumentation group. The mean numbers of vertebrae included in the
      instrumentation were 10.7 and 9.9, respectively. At the two-year follow-up
      evaluation, the mean postoperative Cobb angles were 38 degrees and 25 degrees,
      respectively (p < 0.0001). At the final follow-up evaluation, the mean angles
      were 45 degrees and 32 degrees (p < 0.0001). No significant difference in
      thoracic kyphosis or lumbar lordosis was observed between the study groups at the
      final follow-up evaluation. The average score on the Scoliosis Research Society
      questionnaire was 97 points in both groups. Measurements of non-dynamometric
      trunk strength corresponded with age and sex-adjusted reference values, on the
      average, but patients with Cotrel-Dubousset instrumentation performed
      significantly better in the squatting test (p = 0.010). Abnormal lumbar extension
      and trunk side-bending were significantly more common in the Harrington
      instrumentation group (p = 0.050 and p = 0.0061, respectively). Complications
      were recorded for nine (12%) of the patients treated with Harrington
      instrumentation and fifteen (26%) of those treated with Cotrel-Dubousset
      instrumentation (p = 0.027). CONCLUSIONS: Cotrel-Dubousset instrumentation
      yielded better long-term functional and radiographic outcomes in patients with
      adolescent idiopathic scoliosis than did Harrington instrumentation. However,
      complications were more common in the Cotrel-Dubousset instrumentation group.

PMID- 14668499
TI  - Surgical treatment of limb-length discrepancy following total hip arthroplasty.
AB  - BACKGROUND: Although most patients with limb-length discrepancy following total
      hip arthroplasty have manageable symptoms, others may be disabled as a result of
      pain or functional impairment. In these patients, reoperation may be indicated to
      equalize the limb lengths. There is a paucity of published data regarding the
      outcome of surgical intervention to treat this problem. The purpose of the
      present study was to evaluate the results of revision hip surgery for the
      treatment of symptomatic limb-length discrepancy. METHODS: We retrospectively
      reviewed the clinical and radiographic records of patients who had undergone
      revision hip surgery at our institution for the treatment of a symptomatic limb
      length discrepancy following a previous total hip arthroplasty. We identified
      twenty-one patients (twenty-one hips) who had an average age of sixty-six years
      at the time of revision hip arthroplasty. The average duration of follow-up was
      2.8 years, and no patient was lost to follow-up. The indications for revision hip
      arthroplasty were severe hip and/or back pain for eleven patients, instability of
      the hip for eight, hip pain and ipsilateral limb paresthesia for one, and hip
      pain and ipsilateral foot drop for one. RESULTS: Revision arthroplasty was
      performed at a mean of eight months (range, six days to six years) after primary
      total hip replacement. The mean limb-length discrepancy at the time of the
      revision was 4 cm (range, 2 to 7 cm). Following revision arthroplasty, which
      involved revision of a malpositioned acetabular and/or femoral component,
      equalization of the limb lengths was achieved in fifteen patients. In the
      remaining six patients, the mean discrepancy had decreased to 1 cm. The mean
      Harris hip score improved significantly, from 56.5 points before the revision to
      83.2 points at the time of the latest follow-up (p < 0.005). All but two patients
      were satisfied with the outcome of the revision surgery. CONCLUSIONS: Limb-length
      discrepancy following hip arthroplasty can be associated with pain, paresthesia,
      and hip instability. In these patients, careful evaluation of the position and
      orientation of the components may reveal the cause of the discrepancy. Revision
      arthroplasty may be indicated when a surgically correctable cause of limb-length
      discrepancy can be identified.

PMID- 14668500
TI  - Surgeon experience and clinical and economic outcomes for shoulder arthroplasty.
AB  - BACKGROUND: Previous studies have demonstrated that a high surgical volume for
      certain surgical procedures reduces morbidity and improves economic outcome;
      however, to our knowledge, no study has demonstrated a similar relationship
      between volume and outcome for total shoulder arthroplasty and hemiarthroplasty.
      The objective of this study was to determine whether increased surgeon experience
      was associated with improved clinical and economic outcomes for patients
      undergoing total shoulder arthroplasty or hemiarthroplasty. METHODS: We analyzed
      discharge data on patients treated between 1994 and 2000 from the Maryland Health
      Services Cost Review Commission, which has a statewide hospital discharge
      database of all patients in the state of Maryland. The database included all
      patients undergoing total shoulder arthroplasty and hemiarthroplasty. We assessed
      the relationship between surgeon volume (low, medium, and high) and the risk of
      complications, length of stay, and total charges. The statistics were adjusted
      for procedure, age, gender, race, marital status, comorbidity, diagnosis,
      insurance type, income, and hospital volume. RESULTS: For the 1868 discrete total
      shoulder arthroplasties and hemiarthroplasties done in the state of Maryland, the
      risk of at least one complication associated with the procedures done by the high
      volume surgeon group was nearly half that associated with the procedures done by
      the low-volume surgeon group (adjusted odds ratio, 0.6; 95% confidence interval,
      0.4 to 0.9). High-volume surgeons were three times more likely than were low
      volume surgeons to have patients with a hospital stay of less than six days (odds
      ratio, 0.3; 95% confidence interval, 0.2 to 0.6). Although the average cost of
      hospitalization was $1000 less in the high-volume surgeon group compared with the
      low-volume surgeon group, this reduction did not reach significance after
      adjustment for multiple variables (odds ratio, 0.8; 95% confidence interval, 0.5
      to 1.4). CONCLUSIONS: This study indicates that the patients of surgeons with
      higher average annual caseloads of total shoulder arthroplasties and
      hemiarthroplasties have decreased complication rates and hospital lengths of stay
      compared with the patients of surgeons who perform fewer of these procedures.
      These analyses of hospital discharge data are limited because of a lack of
      prospective data, operative details, and patient outcomes data. However, this
      study emphasizes the importance of continued education for orthopaedic surgeons
      who perform shoulder arthroplasty.

PMID- 14668501
TI  - Comparison of the wear rates of twenty-eight and thirty-two-millimeter femoral
      heads on cross-linked polyethylene acetabular cups in a wear simulator.
AB  - BACKGROUND: The use of larger femoral head sizes in total hip arthroplasty has
      been shown to reduce the rate of dislocation and to increase the range of motion;
      however, such components have been associated with unacceptably high polyethylene
      wear rates. Studies have shown dramatic differences in wear rates between
      nominally cross-linked polyethylene (i.e., polyethylene that is cross-linked
      during radiation sterilization) and elevated cross-linked polyethylene (i.e.,
      polyethylene that is cross-linked to a higher degree than that obtained by
      radiation sterilization alone). The aim of this study was to test the effect of
      increased cross-linking and of increased head size on polyethylene wear rates.
      METHODS: Four groups of acetabular liners obtained from a single manufacturer,
      including 28-mm-diameter nominally cross-linked, 32-mm-diameter nominally cross
      linked, 28-mm-diameter elevated cross-linked, and 32-mm-diameter elevated cross
      linked polyethylene liners, were tested. Three implants from each group were
      tested in a twelve-station hip wear simulator with use of 90% bovine serum as a
      lubricant. The liners were articulated with the appropriately sized cobalt
      chromium femoral head. Additional liners from each design were subjected only to
      the same load without motion to serve as load-soak controls to account for any
      weight gain due to fluid absorption. Gravimetric analysis was performed every
      500,000 cycles for a total of five million cycles. RESULTS: Nominally cross
      linked liners demonstrated mean wear rates of 14.97 and 16.92 mg per million
      cycles for the 28-mm and 32-mm head sizes, respectively. Both of the elevated
      cross-linked liners had significantly lower wear rates than the nominally cross
      linked liners, with a mean of 1.51 and 2.57 mg per million cycles for the 28-mm
      and 32-mm head sizes, respectively (p < 0.001). CONCLUSION: The dramatic
      reduction in wear rates with polyethylene cross-linking, even with the larger
      head size, may increase the potential for use of 32-mm head components in total
      hip arthroplasty.

PMID- 14668502
TI  - In vivo somatic cell gene transfer of an engineered Noggin mutein prevents BMP4
      induced heterotopic ossification.
AB  - BACKGROUND: The formation of the skeleton requires inductive signals that are
      balanced with their antagonists in a highly regulated negative feedback system.
      Inappropriate or excessive expression of BMPs (bone morphogenetic proteins) or
      their antagonists results in genetic disorders affecting the skeleton, such as
      fibrodysplasia ossificans progressiva. BMP signaling mediated through binding to
      its receptors is a critical step in the induction of abnormal ossification.
      Therefore, we hypothesized that engineering more effective inhibitors of this BMP
      signaling process may lead to the development of therapies for such conditions.
      METHODS: BMP4-induced heterotopic ossification was used as a model for testing
      the ability of the BMP antagonist Noggin to block de novo bone formation, either
      by local or systemic delivery. Since Noggin naturally acts locally, a Noggin
      mutein, hNOGDeltaB2, was engineered and was shown to circulate systemically, and
      its ability to block heterotopic ossification was tested in a mouse model with
      use of adenovirus-mediated somatic cell gene transfer. RESULTS: A mouse model of
      BMP4-induced heterotopic ossification was developed. Local delivery of wild-type
      NOG inhibited heterotopic ossification, but systemic administration was
      ineffective. In contrast, systemic delivery of the adenovirus encoding
      hNOGDeltaB2 resulted in systemic levels that persisted for more than two weeks
      and were sufficient to block BMP4-induced heterotopic ossification. CONCLUSIONS:
      BMP4-induced heterotopic ossification can be prevented in vivo either by local
      delivery of wild-type Noggin or after somatic cell gene transfer of a Noggin
      mutein, hNOGDeltaB2. Furthermore, the data in the present study provide proof of
      concept that a naturally occurring factor can be engineered for systemic delivery
      toward a desirable pharmacological outcome. CLINICAL RELEVANCE: Blocking bone
      formation is clinically relevant to disorders of heterotopic ossification in
      humans, such as fibrodysplasia ossificans progressiva. Furthermore, development
      of BMP antagonists as therapeutic agents may provide modalities for the treatment
      of other pathologic conditions that arise from aberrant expression of BMPs and/or
      from a lack of their antagonists.

PMID- 14668503
TI  - A prospective, randomized trial comparing the limited contact dynamic compression
      plate with the point contact fixator for forearm fractures.
AB  - BACKGROUND: The most effective type of plate fixation for diaphyseal forearm
      fractures has not been defined. We performed a prospective, randomized trial in
      which the limited contact dynamic compression plate (LC-DCP) was compared with
      the Point Contact Fixator (PC-Fix) for the treatment of forearm fractures at one
      center. METHODS: Ninety-two patients with 125 forearm fractures were recruited
      for the study and were randomly assigned to fracture fixation with one of the two
      devices. The average age of the patients was thirty-six years. The average
      duration of follow-up was twenty-two months. Patients were assessed periodically
      with use of radiographs and were assessed with regard to pain and function at
      time of the latest follow-up. RESULTS: Three patients (four fractures) in the PC
      Fix group and five patients (five fractures) in the LC-DCP group had a delayed
      union, but no patient in either group had a nonunion. With the numbers available,
      there was no significant difference between the two groups with regard to
      operative time, time to union, callus formation, pain, or functional outcome.
      Deep infection occurred in one patient with a closed fracture in the PC-Fix group
      and in one patient with an open fracture in the LC-DCP group. In addition, one
      refracture occurred in each group. Both refractures occurred at the site of a
      screw track. CONCLUSION: Despite the differences in the concept of fracture
      fixation, these two implants appear to be equally effective for the treatment of
      diaphyseal forearm fractures.

PMID- 14668504
TI  - Correction of sagittal plane spinal deformities with unit rod instrumentation in
      children with cerebral palsy.
AB  - BACKGROUND: To our knowledge, there have been no previous studies addressing the
      indications for and the results of treatment of patients with cerebral palsy and
      concomitant kyphosis or lordosis without scoliosis. The purpose of the present
      study was to identify the indications for and the results of treatment of
      patients with cerebral palsy who have a spinal curve deformity solely in the
      sagittal plane. METHODS: We conducted a retrospective review of the data on all
      patients with cerebral palsy who had a sagittal plane spinal deformity but no
      coronal plane deformity, had undergone posterior spinal fusion with unit rod
      instrumentation at our institution, and had been followed for at least two years.
      Medical records and radiographs were reviewed for symptoms, type and magnitude of
      deformity, age at surgery, duration of surgery, nutritional status,
      complications, and concomitant medical problems. RESULTS: Twenty-four patients
      ten boys and fourteen girls-were identified. Eight patients had a hyperlordotic
      deformity, fourteen had a hyperkyphotic deformity, and two exhibited both.
      Surgical indications included severe seating problems that could not be rectified
      with wheelchair modifications (eighteen patients), severe back pain (four
      patients), superior mesenteric artery syndrome that was refractory to
      conservative treatment (two patients), and a hyperlordotic deformity with a loss
      of bowel and bladder control (one patient). It was found that specific technical
      concerns had to be addressed when the unit rod instrumentation was used. The mean
      preoperative hyperkyphotic curve of 93.8 degrees was corrected to a mean of 35.8
      degrees postoperatively and was a mean of 34.8 degrees at the last visit. The
      mean preoperative hyperlordotic curve of 91.8 degrees was corrected to a mean of
      43.6 degrees postoperatively and was a mean of 48.6 degrees at the last visit.
      All patients with seating problems and back pain had improvement or resolution of
      the problem after the surgery. The superior mesenteric artery syndromes, losses
      of bowel and bladder function, and malnutrition all resolved completely after the
      surgery. CONCLUSIONS: Patients with cerebral palsy and a severe sagittal plane
      deformity (> or =70 degrees ) can be treated successfully with posterior spinal
      fusion with use of unit rod instrumentation. Indications for treatment include
      loss of sitting ability or balance, back pain, loss of bowel or bladder function,
      and superior mesenteric artery syndrome that is unresponsive to medical
      management.

PMID- 14668505
TI  - Ganz reinforcement ring for reconstruction of acetabular defects in revision
      total hip arthroplasty.
AB  - BACKGROUND: In revision total hip arthroplasty, bone loss due to loosening and
      migration of the acetabular component makes fixation of a new implant difficult.
      The purpose of this study was to evaluate the clinical and radiographic outcomes
      of the use of the Ganz reinforcement ring with nonstructural allograft in the
      reconstruction of acetabular defects. METHODS: Sixty-one acetabular revisions
      performed with use of the Ganz reinforcement ring and nonstructural allograft,
      between 1989 and 1992, in fifty-seven patients with aseptic loosening met our
      selection criteria. Eleven hips in eleven patients were lost to follow-up,
      leaving fifty hips available for evaluation five years or more following surgery.
      According to the American Academy of Orthopaedic Surgeons classification, twenty
      four acetabular defects were Type II, twenty-four were Type III, and two were
      Type IV. Clinical and radiographic evaluations were carried out at a mean of six
      and nine years after surgery. Twelve more patients were lost to follow-up before
      the most recent evaluation. RESULTS: The mean Merle d'Aubigne composite score
      increased significantly compared with the preoperative score (p < 0.001). There
      were seven failures: six cases of aseptic loosening and one case of septic
      arthritis. Graft incorporation and bone remodeling occurred in all hips but three
      in which the ring fixation had been inadequate at the time of surgery. The Kaplan
      Meier survivorship rate, with use of revision or loosening of the component as
      the criterion of failure, was 81% at ten years. Inadequate fixation of the
      implant at the time of surgery was the only multivariate predictor of failure (p
      = 0.003). CONCLUSIONS: Patients treated with acetabular revision with a Ganz
      reinforcement ring had reconstitution of periacetabular bone stock as well as
      good clinical and radiographic results, provided that the ring had been fixed
      adequately at the time of surgery. This procedure may not be the preferred
      approach for reconstructing segmental defects of the medial wall or pelvic
      discontinuity.

PMID- 14668506
TI  - Extracortical bone bridging in tumor endoprostheses. Radiographic and histologic
      analysis.
AB  - BACKGROUND: Aseptic loosening remains a major problem following prosthetic
      replacement after resection of periarticular tumors. Attempts to decrease the
      rate of loosening led to the introduction of a composite segmental prosthesis in
      which the shoulder of the intramedullary stem is porous-coated to allow
      extracortical bone bridging and bone ingrowth. The purposes of this study were to
      determine the extent of extracortical bone bridging around, and the amount of
      bone growth into, the porous-coated shoulder of endoprostheses implanted
      following the resection of periarticular bone tumors and to correlate the
      radiographic and histologic findings. METHODS: Twenty tumor endoprostheses
      implanted with use of the extracortical bone-bridging technique were evaluated
      radiographically to determine the extent of extracortical bone and the amount of
      bone ingrowth. Five of these endoprostheses were retrieved and subjected to
      histologic analysis with backscattered electron microscopy and transmitted light
      microscopy to determine the extent of bone ingrowth. RESULTS: At a mean of twenty
      eight months postoperatively, varying amounts of extracortical bone formation
      were seen radiographically in all patients. Radiographs also appeared to show
      bone growth into the porous-coated segment of all implants. However, histologic
      analysis of the five retrieved prostheses revealed that none of the extracortical
      bone had actually grown into the porous-coated segment of the implant.
      CONCLUSIONS: This study confirmed that autogenous bone-grafting of the bone
      implant junction of a tumor endoprosthesis consistently results in the formation
      of extracortical bone. Although radiographs seemed to indicate that this bone
      grows into the porous coating, this was not confirmed histologically. Growth of
      extracortical bone into the extramedullary, porous-coated portion of tumor
      endoprostheses in humans may not be attainable with the current prosthetic design
      and surgical technique.

PMID- 14668507
TI  - Osteoporosis and vitamin-D deficiency among postmenopausal women with
      osteoarthritis undergoing total hip arthroplasty.
AB  - BACKGROUND: Several epidemiological studies have shown a lower prevalence of
      osteoporotic hip fractures in patients with osteoarthritis. Other studies have
      demonstrated elevated bone mineral density in patients with osteoarthritis. The
      prevailing view is that there may be an inverse relationship between
      osteoarthritis and osteoporosis. The purposes of the present study were to
      describe a subgroup of patients with osteoarthritis who were found to have
      osteoporosis and to assess the vitamin-D status and other risk factors for low
      bone density in osteoarthritic subjects with and without osteoporosis. METHODS:
      The bone mineral density of the spine, the proximal part of the femur, and the
      total body was measured with dual-energy x-ray absorptiometry in sixty-eight
      postmenopausal white women who were scheduled to undergo total hip replacement
      for advanced osteoarthritis. The serum levels of 25-hydroxyvitamin D, 1,25
      dihydroxyvitamin D, intact parathyroid hormone, osteocalcin, and bone-specific
      alkaline phosphatase and the urinary level of N-telopeptide were measured.
      Information from validated lifestyle, dietary, and demographic questionnaires was
      also evaluated. RESULTS: Seventeen (25%) of the sixty-eight women had occult
      osteoporosis (as indicated by a T score of less than -2.5). Fifteen (22%) of the
      sixty-eight subjects had vitamin-D deficiency, and three (4%) had an elevated
      serum parathyroid hormone level. Only two of the seventeen osteoporotic women had
      vitamin-D deficiency. On the basis of these numbers, vitamin-D status was not
      correlated with bone density (p = 0.32). Analysis of the relationship between the
      number of years since menopause and osteoporosis or markers of elevated bone
      turnover showed that osteoporosis was detected throughout the postmenopausal
      period. CONCLUSION: A substantial portion of these sixty-eight white women with
      osteoarthritis of the hip had occult osteoporosis and hypovitaminosis D. Vitamin
      D deficiency was not restricted to the group with low bone density. These results
      support the need to consider the presence of both osteoporosis and vitamin-D
      deficiency in women with advanced osteoarthritis.

PMID- 14668508
TI  - Accuracy of measurement of polyethylene wear with use of radiographs of total hip
      replacements.
AB  - BACKGROUND: Although a number of methods are used to estimate polyethylene liner
      wear from radiographs of total hip replacements, there is no consensus with
      regard to the accuracy of these methods. The purpose of this study was to compare
      the accuracy of several such measurement methods with use of both laboratory
      radiographs and routine clinical radiographs. METHODS: A phantom apparatus was
      designed to simulate random values of three-dimensional wear, with varying
      degrees of cup abduction and anteversion, and to obtain anteroposterior and cross
      table lateral radiographs with each value. Wear was measured with use of the
      Charnley duoradiographic method, the Livermore method, and the method described
      by Dorr and Wan, as well as with use of PolyWare and Hip32 software packages,
      both with and without three-dimensional measurements. Clinical wear was measured
      from conventional radiographs made prior to revision surgery in fourteen patients
      and was compared with wear measured directly from the retrieved liners with use
      of a coordinate measuring machine. RESULTS: With laboratory radiographs, median
      errors were 0.1 mm with the Livermore method and both computerized methods, 0.23
      mm with the Charnley method, and 1.7 mm with the method of Dorr and Wan. Maximum
      errors were between 0.6 mm (Livermore) and 4.3 mm (Dorr and Wan). In contrast,
      with use of clinical radiographs, median errors ranged between 0.2 mm (Hip32) and
      0.6 mm (Dorr and Wan). Maximum errors ranged between 1.8 mm (Dorr and Wan) and
      2.5 mm (Livermore). CONCLUSIONS: With laboratory radiographs, computerized
      methods of polyethylene wear measurement offered distinctly greater accuracy than
      did manual methods; however, with clinical radiographs, they offered only
      slightly better accuracy. Although the increased accuracy of computerized methods
      may be necessary in research settings, manual methods provided sufficient
      accuracy for routine clinical assessment of wear.

PMID- 14668509
TI  - Extended trochanteric osteotomy in complex primary total hip arthroplasty. A
      brief note.
AB  - BACKGROUND: The extended trochanteric osteotomy has been a useful approach for
      patients undergoing revision total hip arthroplasty; however, it has not been
      well described as an approach for those undergoing complex primary total hip
      arthroplasty. The purpose of the present report is to describe our experience
      with the use of an extended trochanteric osteotomy for patients undergoing
      complex primary total hip arthroplasty. METHODS: Six patients underwent primary
      total hip arthroplasty with use of an extended trochanteric osteotomy. The
      reasons for the use of this technique included severe femoral deformity, removal
      of intraosseous hardware, and high-riding developmental hip dysplasia. A fully
      porous-coated femoral component with diaphyseal fixation was used for all
      reconstructions. The mean age of the patients at the time of surgery was fifty
      six years. Clinical and radiographic evaluation was performed at a minimum of two
      years. RESULTS: After a mean duration of follow-up of fifty months, all patients
      had an osseointegrated, stable femoral component. The site of the extended
      trochanteric osteotomy healed in five of the six patients. One patient had
      nonunion at the osteotomy site and a fracture at the base of the greater
      trochanter, with a subsequent fracture of the femoral component. The mean Merle
      D'Aubigne and Postel pain and walking scores improved from 2.2 and 2.3
      preoperatively to 5.3 and 4.7 at the time of the final follow-up (p < 0.001).
      CONCLUSIONS: The extended trochanteric osteotomy is useful for the correction of
      femoral deformity and facilitates the removal of intraosseous hardware in
      carefully selected patients undergoing complex primary total hip arthroplasty.

PMID- 14668510
TI  - Chronic rotator cuff injury and repair model in sheep.
AB  - BACKGROUND: Most rotator cuff surgery is performed on chronic tears. As there is
      no animal model in which to examine the physiology of muscle and tendon injury
      and repair in this setting, we developed a chronic rotator cuff injury model in
      sheep. METHODS: The infraspinatus tendon was released in thirty-six female sheep.
      Biopsy specimens were obtained from the muscle and were analyzed for fat content.
      The force generated by the muscle with supramaximal stimulation was recorded
      intraoperatively. A control group (twelve sheep) underwent an immediate tendon
      repair. In the remaining twenty-four sheep, the tendon was wrapped in a dura
      substitute to prevent scarring and was repaired at six weeks (eight sheep) and
      eighteen weeks (sixteen sheep) after release. In the immediate repair group, four
      animals were killed at six weeks; four, at twelve weeks; and four, at twenty
      weeks. In the six-week delayed repair group, four animals were killed at twelve
      weeks and four were killed at twenty weeks after the repair. In the eighteen-week
      delayed repair group, eight animals were killed at twelve weeks; four, at twenty
      weeks; and four, at thirty weeks after the repair. Muscle biopsies and testing
      were repeated prior to killing of the animals. RESULTS: The average force of
      muscle contraction decreased 3.6 lb (1.6 kg) by six weeks after the injury and
      3.9 lb (1.8 kg) by eighteen weeks after the injury. After the repair, the force
      of contraction in the six-week group improved by 0.8 lb (0.4 kg) at twelve weeks
      postoperatively and by 1.3 lb (0.6 kg) at twenty weeks postoperatively. In
      contrast, no improvement occurred in the eighteen-week group until thirty weeks
      after the repair, at which time a 0.9-lb (0.4-kg) improvement was noted. There
      was a twelvefold increase in intramuscular fat concentration; this lipid
      infiltration was partially reversed after the tendon repair. Isolated tendon
      samples demonstrated an increase in the modulus of elasticity after chronic
      detachment that partially corrected after the tendon repair in the earlier (six
      week) repair group. CONCLUSIONS: We found that earlier repair of the tendon
      results in a more rapid recovery of both muscle function and tendon elasticity
      compared with a more delayed repair. We concluded that there may be a "point of
      no return" in rotator cuff injury after which the elasticity of the muscle-tendon
      unit does not return to normal.

PMID- 14668511
TI  - Forearm and elbow injury: the influence of rotational position.
AB  - BACKGROUND: The purpose of this study was to develop an axial loading forearm
      fracture model and to determine the influence of forearm rotation on the fracture
      pattern. METHODS: Twenty-six cadaveric arms were thawed in saline solution.
      Pressure-sensitive film was sealed and was placed through a lateral arthrotomy
      into the radiocapitellar joint. The arm was potted at the proximal part of the
      humerus with the elbow in extension. Rotational range of motion was measured with
      use of a goniometer starting from a supinated position (0 degrees ). Specimens
      were placed in a vertical position at various angles of forearm rotation, and a
      27-kg mass was raised to 90 cm and was dropped onto the distal part of the
      radius. The pressure film was removed and was analyzed to determine the
      radiocapitellar joint contact area following impact. Each arm was dissected, and
      the injury pattern was assessed. RESULTS: Both-bone forearm fractures (proximal
      radial fractures with concomitant distal ulnar fractures) occurred at 5 degrees
      +/- 2.6 degrees of rotation, isolated radial head fractures occurred at 44.4
      degrees +/- 5.2 degrees of rotation, and Essex-Lopresti fractures (radial head
      fractures with tearing of the interosseous membrane) occurred at 70 degrees +/-
      25.2 degrees of rotation. The distribution of Essex-Lopresti and radial head
      fractures was significantly different at a cutpoint of 54 degrees of forearm
      rotation (p = 0.009), and the distribution of radial head fractures and both-bone
      forearm fractures was significantly different at a cutpoint of 10 degrees of
      forearm rotation (p = 0.001). The percent contact area of the radial head varied
      with the injury pattern (p = 0.029). Marginal radial head fractures occurred at
      46.7 degrees +/- 6.6 degrees of rotation with a contact area of 30.9% +/- 8.6%,
      while comminuted radial head fractures occurred at 74.4 degrees +/- 27.2 degrees
      of rotation with a contact area of 53.9% +/- 8.3%. CONCLUSION: The amount of
      forearm rotation at the time of axial load impact directly influenced the injury
      pattern. Furthermore, the radial head contact area and the fracture severity
      increased in pronation compared with supination.

PMID- 14668512
TI  - Evaluation of contemporary software methods used to quantify polyethylene wear
      after total hip arthroplasty.
AB  - BACKGROUND: Radiographic measurements of the wear of total hip arthroplasty
      implants are indirect measurements based on radiographic determinations of the
      location of the femoral head relative to the acetabular component. Using the
      simplest case of zero wear, we assessed the reproducibility and accuracy of two
      software applications designed to quantify wear from clinical radiographs.
      METHODS: After a cobalt-chromium head was glued into the polyethylene liner of a
      titanium shell, one cross-table lateral radiograph and three anteroposterior
      pelvic radiographs were made for twelve permutations of acetabular component
      angulation. The three anteroposterior radiographs differed only with regard to
      the cephalocaudal positioning of the prosthesis relative to the x-ray tube. To
      assess method reproducibility, each anteroposterior radiograph was assumed to be
      both the initial and the latest follow-up radiograph of a wear analysis. To
      assess method accuracy, each anteroposterior radiograph was paired in a wear
      analysis with each of the two anteroposterior radiographs made when the component
      was in the same angulation but at a different cephalocaudal position relative to
      the tube (one radiograph was the initial follow-up radiograph while the second
      was the latest follow-up radiograph). The analyses of reproducibility and
      accuracy were performed both with and without inclusion of the lateral radiograph
      made with the component in the same angulation. RESULTS: Both methods fared well
      in the reproducibility analyses, with mean linear and volumetric wear values of
      0.00 to 0.07 mm and 0 to 24 mm(3), respectively. In the accuracy analyses, the
      mean linear and volumetric wear values derived with the two methods were 0.26 to
      0.40 mm and 78 to 126 mm(3), respectively. CONCLUSIONS: Whereas the results of
      the reproducibility analyses showed that the methods were consistent in
      determining the relative positions of the head and shell from a given
      anteroposterior radiograph or pair of anteroposterior and lateral radiographs,
      the non-zero wear results obtained in the accuracy analyses proved that these
      positional determinations were often inaccurate. Thus, while contemporary
      software methods may yield reproducible results, their accuracy is limited by
      their inability to correctly determine the position of the head relative to the
      acetabular component.

PMID- 14668513
TI  - Magnetic resonance imaging of patellofemoral kinematics with weight-bearing.
AB  - BACKGROUND: Previous studies of the patellofemoral joint have been limited by the
      use of invasive techniques, measurements under non-weight-bearing conditions,
      cadaveric specimens, or computerized models. It has been shown that soft tissue
      and bone can be accurately quantified with magnetic resonance imaging. The
      present study was designed to define the relationship between the patellofemoral
      contact area and patellofemoral kinematics in vivo. METHODS: Ten subjects with
      clinically normal knee joints were scanned with high-resolution magnetic
      resonance imaging while they pushed a constant weight (133 N) on the foot-plate
      of a custom-designed load-bearing apparatus. Images were obtained at five
      positions of flexion between -10 degrees and 60 degrees. Three-dimensional
      reconstructions were used to measure the patellofemoral cartilage contact area,
      patellar centroid, patellar medial and inferior translation, patellar medial and
      inferior tilt, and patellar varus-valgus rotation. All translation and area
      measurements were normalized on the basis of the interepicondylar distance.
      Random-effects models of quadratic regressions were used to evaluate the data.
      RESULTS: The mean contact area ranged from 126 mm(2) in extension to 560 mm(2) at
      60 degrees of flexion. The patella translated inferiorly to a maximum distance of
      34 mm at 60 degrees of flexion and translated medially to a maximum distance of
      3.2 mm at 30 degrees of flexion before returning to nearly 0 mm at 60 degrees of
      flexion. The patella tilted inferiorly to a mean of nearly 35 degrees at 60
      degrees of flexion and medially to a maximum of 4.2 degrees at 30 degrees of
      flexion. By 60 degrees of flexion, the centroid of the contact area had shifted
      to an inferior and posterior maximum of 20 and 10 mm, respectively. CONCLUSIONS:
      We found that lateral patellar subluxation and tilt occurred in these normal
      knees at full extension and the patella was reduced into the trochlear groove at
      30 degrees of flexion. Therefore, we believe that lateral patellar tilt and
      subluxation observed during arthroscopy of the extended knee may not represent a
      pathological condition.

PMID- 14668514
TI  - Intramedullary rod fixation compared with blade-plate-and-screw fixation for
      tibiotalocalcaneal arthrodesis: a biomechanical investigation.
AB  - BACKGROUND: Achieving stable fixation when performing tibiotalocalcaneal
      arthrodesis can be challenging, especially in osteopenic bone. The purpose of the
      current investigation was to compare the stiffness and fatigue endurance of blade
      plate-and-screw fixation with intramedullary rod fixation in a cadaveric model.
      METHODS: In ten matched pairs of fresh-frozen cadaveric legs, a
      tibiotalocalcaneal arthrodesis was performed with use of a blade-plate and a 6.5
      mm sagittal screw in one leg and with use of an intramedullary rod in the
      contralateral leg. After an initial load-deformation curve was obtained, each
      specimen was loaded to 270 N through 250,000 cycles at a rate of 3 Hz. RESULTS:
      Blade-plate-and-screw fixation resulted in significantly higher mean initial and
      final stiffness and decreased plastic deformation than did intramedullary rod
      fixation. In addition, there was an inverse correlation between bone-mineral
      density and the difference in plastic deformation noted between the specimens of
      each pair. CONCLUSIONS: Blade-plate fixation is biomechanically superior to
      intramedullary fixation for tibiotalocalcaneal arthrodesis.

PMID- 14668515
TI  - Preserving limb length with an osteomyocutaneous autograft salvaged from the
      surgical specimen. A case report.

PMID- 14668516
TI  - Periprosthetic knee joint infection following colonoscopy. A case report.

PMID- 14668517
TI  - Periarticular aneurysm following total knee replacement in hemophilic
      arthropathy. A case report.

PMID- 14668518
TI  - Nonunion of a triquetral body fracture. A case report.

PMID- 14668519
TI  - Hemarthrosis associated with failure of a mobile meniscal-bearing total knee
      arthroplasty. A case report.

PMID- 14668522
TI  - Great to greater: opportunities and challenges for the American Orthopaedic
      Association in the early twenty-first century. Challenges in our academic
      mission.

PMID- 14668520
TI  - Understanding the limitations of the journal impact factor.
AB  - The impact factor, a simple mathematical formula reflecting the number of
      citations of a journal's material divided by the number of citable materials
      published by that same journal, has evolved to become one of the most influential
      tools in modern research and academia. The impact factor can be influenced and
      biased (intentionally or otherwise) by many factors. Extension of the impact
      factor to the assessment of journal quality or individual authors is
      inappropriate. Extension of the impact factor to cross-discipline journal
      comparison is also inappropriate. Those who choose to use the impact factor as a
      comparative tool should be aware of the nature and premise of its derivation and
      also of its inherent flaws and practical limitations.

PMID- 14668523
TI  - Women in surgical residency training programs.
AB  - BACKGROUND: Increasing numbers of women are entering surgical fields. The purpose
      of this study was to assess whether orthopaedic surgery is significantly
      different from other surgical fields in the recruitment of women to training
      programs. METHODS: We analyzed data from the American Association of Medical
      Colleges as reported in annual issues on medical education in the Journal of the
      American Medical Association for the years 1970 to 2001, excluding 1975. Using
      linear regression models, we analyzed two factors: changes in the percentage of
      women within orthopaedic residencies (i.e., the ratio of men to women) and
      changes in the percentage of all female residents who choose to enter
      orthopaedics compared with other types of surgical residencies. RESULTS: The
      percentage of women in the entering classes of medical school has increased from
      11.1% in 1970 to 47.8% in 2001, while the percentage of women in orthopaedics has
      increased from 0.6% in 1970 to 9.0% in 2001. Orthopaedic residencies have the
      lowest percentage of women compared with all other primary surgical specialties.
      Only thoracic surgery, a field entered secondarily after the completion of
      general surgical training, has a lower percentage. The increases in the
      percentage of women in orthopaedics over the past thirty years have been
      significantly lower than those in every other primary surgical field (including
      general surgery, obstetrics and gynecology, ophthalmology, otolaryngology, and
      urology), except neurosurgery, and are markedly different from the percentages of
      women in the entering classes of medical school. The percentage of all female
      residents who choose an orthopaedic residency is 0.6%, a number that has not
      changed over the past twenty years. CONCLUSIONS: Orthopaedic surgery has not had
      the same success in recruiting female trainees that other surgical fields have
      had. Furthermore, there appears to be a leveling of the recruitment rate over the
      past two decades, indicating that the higher numbers of women entering medicine
      will not be sufficient to improve gender representation in orthopaedic surgery
      training.

PMID- 14668524
TI  - Quantifying the extent of femoral head involvement in osteonecrosis.

PMID- 14668525
TI  - Accuracy of needle placement into the intra-articular space of the knee.

PMID- 14668526
TI  - Magnetic resonance imaging of the rheumatic cervical spine.

PMID- 14668527
TI  - Patellar resurfacing in total knee arthroplasty.

PMID- 14668528
TI  - Granulomatous inflammation after Hylan G-F 20 viscosupplementation of the knee.

PMID- 14668529
TI  - Preoperative autologous donation for hip replacement.

PMID- 14668530
TI  - Autologous chondrocyte implantation and osteochondral cylinder transplantation in
      cartilage repair of the knee joint.

PMID- 14668531
TI  - Slipping or recurrent dislocation of the patella: with the report of eleven
      cases. American Journal of Orthopedic Surgery, Vol. 1, pp. 293-308, 1903.

PMID- 14668532
TI  - TOR signaling.
AB  - The mammalian target of rapamycin, mTOR, is a protein Ser-Thr kinase that
      functions as a central element in a signaling pathway involved in the control of
      cell growth and proliferation. The activity of mTOR is controlled not only by
      amino acids, but also by hormones and growth factors that activate the protein
      kinase Akt. The signaling pathway downstream of Akt leading to mTOR involves the
      protein products of the genes mutated in tuberous sclerosis, TSC1 and TSC2, and
      the small guanosine triphosphatase, Rheb. In cells, mTOR is found in a complex
      with two other proteins, raptor and mLST8. In this review, we describe recent
      progress in understanding the control of the mTOR signaling pathway and the role
      of mTOR-interacting proteins.

PMID- 14668534
TI  - The expression of spinach glycolate oxidase (GO) in E. coli and the application
      of GO in the production of glyoxylic acid.
AB  - The complementary deoxyribonucleic acid (cDNA) coding spinach glycolate oxidase
      (GO) was amplified by reverse transcription polymerase chain reaction (RT-PCR),
      using the total ribonucleic acid (RNA) of spinach leaves as the template, and was
      cloned into cloning vector pMD18-T. After the DNA sequence was determined, the go
      gene was subcloned into Escherichia coli expression vectors. Sodium dodecyl
      sulfatepolyacrylamide gel electrophoresis (SDS-PAGE) analysis showed that
      recombinant GO was expressed in E. coli BL21 (DE3)(pTIG-Trx-GO) and E. coli BL21
      (DE3)(pET-22b(+)-GO). The result of the enzyme activity assay and the oxidation
      of glycolate to glyoxylate catalyzed by the whole cells of E. coli BL21 (DE3)(pET
      22b(+)-GO) proved the feasibility of using E. coli cells to produce glyoxylic
      acid.

PMID- 14668535
TI  - Expression and purification of a novel mannose-binding lectin from Pinellia
      ternata.
AB  - Pinellia ternata agglutinin (PTA) from the tubers of P. ternata is a monocot
      mannose-binding lectin that catalytically agglutinated rabbit erythrocytes. The
      potential effect of PTA has gained considerable interest in recent years owing to
      clinical use of native PTA as the preparation against cancer and for plant
      protection against insect pests. Here we report a successful strategy to allow
      high-level expression of PTA as inclusion bodies in Escherichia coli M15.
      Purification of refolded recombinant protein from solubilized inclusion bodies by
      Ni-NTA agarose affinity chromatography yielded biological activity recombinant
      PTA (final yield of about 10 mg/L). The recombinant PTA agglutinated rabbit
      erythrocytes to a dilution similar to that determined for "native" lectin
      purified from P. ternata. The expression and purification system makes it
      possible to obtain sufficient quantities of biologically active and homogenous
      recombinant PTA sufficient to carry out advanced clinical trials. This is the
      first report on the large-scale expression and purification of biologically
      active recombinant PTA from E. coli.

PMID- 14668536
TI  - Single-base discrimination mediated by proofreading 3' phosphorothioate-modified
      primers.
AB  - It has been well known for decades that deoxyribonucleic acid (DNA) polymerases
      with proofreading function have a higher fidelity in primer extension as compared
      to those without 3' exonuclease activities. However, polymerases with
      proofreading function have not been used in single nucleotide polymorphism (SNP)
      assays. Here, we describe a new method for single-base discrimination by
      proofreading the 3' phosphorothioate-modified primers using a polymerase with
      proofreading function. Our data show that the combination of a polymerase with 3'
      exonuclease activity and the 3' phosphorothioate-modified primers work
      efficiently as a single-base mismatch-operated on/off switch. DNA polymerization
      only occurred from matched primers, whereas mismatched primers were not extended
      at the broad range of annealing temperature tested in our study. This novel
      single-base discrimination method has potential in SNP assays.

PMID- 14668537
TI  - Blockade of plasmid replication mediated by peptide nucleic acids.
AB  - Because peptide nucleic acids (PNAs) are capable of blocking amplification of
      deoxyribonucleic acid (DNA) by Taq DNA polymerase in vitro, we postulated that
      PNAs might be able to block replication in vivo. To explore this possibility, we
      assessed the ability of PNA to specifically block the replication of pUC19
      plasmids by allowing a PNA, directed against segments of the Ampr sequence to
      bind to pUC19 prior to electroporation into Escherichia coli, strain DH10B.
      Colonies produced by this maneuver not only remained sensitive to ampicillin but
      were also incapable of blue color production on X-gal-containing media, thus
      demonstrating true blockade of pUC19 replication, rather than antisense activity.
      The ability of the PNA to prevent pUC19 replication in these experiments was
      shown to be dose related. Attempts to prevent the replication of E. coli using a
      PNA directed against a portion of the lac Z sequence found within the bacterial
      genome were not uniformly successful. Subsequent experiments showed that the
      electroporated PNA did not consistently enter a sufficient number of cells for an
      effect to be demonstrated in the assays used. Nonetheless, this is the first
      demonstration of in vivo complete replication blockade by a PNA and opens up the
      potential for new forms of specific antibiosis in both prokaryotic and eukaryotic
      cells.

PMID- 14668538
TI  - Structural basis of matrix metalloproteinases and tissue inhibitors of
      metalloproteinases.
AB  - The matrix metalloproteinases (MMPs) constitute a family of secreted/cell-surface
      anchored multidomain zinc endopeptidases, all of which exhibit a catalytic domain
      of a common metzincin-like topology, and which are involved in degradation of the
      extracellular matrix but also in a number of other biologic processes. Normally,
      the proteolytic activity of the MMPs is precisely regulated by their main
      endogenous protein inhibitors, in particular the tissue inhibitors of
      metalloproteinases (TIMPs). Disruption of this balance results in serious
      diseases such as arthritis, tumor growth, and tumor metastasis, rendering the
      MMPs attractive targets for inhibition therapy. Knowledge of their tertiary
      structures is crucial for a full understanding of their functional properties and
      their associations with dysfunctions. Since the reports of the first atomic
      structures of MMPs and TIMPs in 1994, considerable structural information has
      become available about both of these families of substances. Many of the MMP
      structures have been determined as complexes with synthetic inhibitors,
      facilitating knowledge-based drug design. This review focuses on the currently
      available 3D structural information about MMPs and TIMPs.

PMID- 14668539
TI  - The use of hydrolysis and hairpin probes in real-time PCR.
AB  - In this review we discuss the limitations of traditional PCR methods and
      introduce real-time PCR, a fluorescence-based detection system, as a method that
      overcomes these limitations. We describe the technologies involved in real-time
      PCR including the design of hydrolysis and hairpin probes and the practical
      applications of such systems.

PMID- 14668540
TI  - Advances in pharmacogenomic research and development.
AB  - Technological achievements in the last 5 to 10 yr and their application to
      sequencing and polymorphism discovery in the human genome have fostered a renewed
      interest in the genetic basis of drug response. Consequently, the field of
      pharmacogenetics/pharmacogenomics has been gaining momentum, fueled not only on
      technology but also on results of empirical studies of the human genome and on
      genetic epidemiology studies of real drugs in patient populations. This review
      discusses some of the recent advances in pharmacogenomic research and development
      over the last few years that include understanding the architecture of the human
      genome, the creation of population deoxyribonucleic acid (DNA)/data banks,
      assessment of the clinical validity of genetic markers, and experience with
      regulatory aspects of pharmacogenomics.

PMID- 14668541
TI  - Typing single-nucleotide polymorphisms using a gel-based sequencer: a new data
      analysis tool and suggestions for improved efficiency.
AB  - Single-nucleotide polymorphisms (SNPs) are increasingly used as genetic markers.
      Although a high number of SNP-genotyping techniques have been described, most
      techniques still have low throughput or require major investments. For
      laboratories that have access to an automated sequencer, a single-base extension
      (SBE) assay can be implemented using the ABI SNaPshot trade mark kit. Here we
      present a modified protocol comprising multiplex template generation, multiplex
      SBE reaction, and multiplex sample analysis on a gel-based sequencer such as the
      ABI 377. These sequencers run on a Macintosh platform, but on this platform the
      software available for analysis of data from the ABI 377 has limitations. First,
      analysis of the size standard included with the kit is not facilitated. Therefore
      a new size standard was designed. Second, using Genotyper (ABI), the analysis of
      the data is very tedious and time consuming. To enable automated batch analysis
      of 96 samples, with 10 SNPs each, we developed SNPtyper. This is a spreadsheet
      based tool that uses the data from Genotyper and offers the user a convenient
      interface to set parameters required for correct allele calling. In conclusion,
      the method described will enable any lab having access to an ABI sequencer to
      genotype up to 1000 SNPs per day for a single experimenter, without investing in
      new equipment.

PMID- 14668542
TI  - Apoptosis, proliferation, and expression of p53 and bcl-2 in endocervical
      glandular intraepithelial lesions and invasive endocervical adenocarcinoma.
AB  - We evaluated apoptosis, proliferation, and p53 and bcl-2 expression in a spectrum
      of intraepithelial and invasive endocervical glandular lesions currently
      recognized by the World Health Organization as adenocarcinoma in situ, lesions
      with atypia "less than adenocarcinoma in situ" (endocervical glandular dysplasia
      and endocervical glandular atypia), and invasive adenocarcinoma. Aside from
      nuclear atypia, increased mitotic activity and apoptosis are consistent and
      closely correlated morphologic features of endocervical adenocarcinoma in situ.
      Apoptotic bodies and mitotic figures were counted in 32 examples of normal
      endocervical glands, 35 of endocervical glandular atypia, 30 of endocervical
      glandular dysplasia, 34 of adenocarcinoma in situ, and 30 of invasive
      adenocarcinoma. These results were correlated with immunohistochemical staining
      for MIB1, bcl-2, and p53 performed on 20 examples of each. Mitotic counts, p53
      expression, and bcl-2 expression all increased significantly and in proportion to
      the degree of atypia in the spectrum of endocervical lesions. Apoptotic body
      counts and MIB1 expression also increased significantly with increasing atypia,
      but showed higher levels in adenocarcinoma in situ than in invasive
      adenocarcinoma. Apoptosis correlates with proliferation as measured by mitotic
      counts and MIB1, and also with p53 and bcl-2 expression. Apoptosis appears to be
      an important mechanism in the pathogenesis of endocervical glandular lesions and
      may be useful as an aid in their evaluation and diagnosis.

PMID- 14668543
TI  - Utility of HPV analysis for evaluation of possible metastatic disease in women
      with cervical cancer.
AB  - In a woman with cervical cancer and a distant lesion, the histologic distinction
      of metastatic cervical cancer versus another primary tumor or metastases from
      another cancer can be difficult and has important clinical implications. Criteria
      for inclusion in the study were a history of primary cervical cancer and a new
      lesion in which the pathologic differential diagnosis was metastatic cervical
      cancer versus new primary versus metastatic ovarian carcinoma. Ten cases were
      identified. The cervical cancers and the other lesion(s) were tested for human
      papillomavirus DNA by in situ hybridization and human papillomavirus RNA (E6/E7)
      by reverse transcriptase in situ polymerase chain reaction. Human papillomavirus
      DNA was detected in the primary cervical cancer by in situ hybridization in five
      of nine cases; viral RNA was detected by reverse transcriptase in situ polymerase
      chain reaction in nine of nine cases (one case was not available for viral
      testing). In six cases, human papillomavirus was detected in the subsequent
      lesion (three lung, one cervical lymph node, two retroperitoneum), documenting
      the latter was metastatic cervical cancer. Human papillomavirus was not detected
      in the other four cases (two lung, two retroperitoneum in women with ovarian
      cancer), documenting that they were either primary lung cancers or metastatic
      ovarian cancers, respectively. Reverse transcriptase in situ polymerase chain
      reaction for human papillomavirus RNA is a reliable method to differentiate
      metastatic cervical carcinoma from either a new primary tumor or a metastasis
      from another cancer.

PMID- 14668544
TI  - Overexpression/amplification of HER-2/neu is uncommon in invasive carcinoma of
      the uterine cervix.
AB  - The aim of this study was to investigate HER-2/neu (c-erbB2)
      overexpression/amplification in carcinoma of the uterine cervix using
      immunohistochemistry and fluorescent in situ hybridization (FISH) to assess
      whether anti-p185c-erbB2 therapy might have potential benefits in patients with
      advanced invasive cervical carcinoma. The authors used a protocol for p185c-erbB2
      immunohistochemistry (clone CB11) that has been previously calibrated using FISH
      as the gold standard, showing a 98% accuracy rate in a large series of breast
      carcinomas. Immunolabeling for p185c-erbB2 was present in 24 of 82 (29%) of the
      tumors, but only 2 tumors (2%) with a labeling of more than 60% of the cells were
      considered positive for overexpression. FISH analysis did not find HER-2/neu gene
      amplification in these cases, although five other tumors showed weak and/or focal
      immunolabeling. There was no correlation between the presence of immunolabeling
      and age, histologic type, or clinical stage. Overexpression/amplification of HER
      2/neu is uncommon in invasive cervical carcinoma, suggesting that there is little
      indication for using anti-p185c-erbB2 therapy in the treatment of these patients.

PMID- 14668545
TI  - Molecular analysis of endometrial hyperplasia in HNPCC-suspicious patients may
      predict progression to endometrial carcinoma.
AB  - Women predisposed to hereditary nonpolyposis colorectal cancer are at high risk
      of developing endometrial carcinoma at a young age. Hereditary nonpolyposis
      colorectal cancer-associated endometrial carcinomas are of the endometrioid type,
      usually arise from complex atypical hyperplasia, and often show microsatellite
      instability. To identify occult hereditary nonpolyposis colorectal cancer
      individuals among endometrial carcinoma patients, we examined complex atypical
      hyperplasias and endometrial carcinomas of 60 women < or =50 years of age (mean
      age: 35.7 years) using microsatellite instability, immunohistochemistry, and DNA
      sequence analysis. Three patient groups were recruited: group 1, patients with
      complex atypical hyperplasia exclusively (n = 27); group 2, patients with complex
      atypical hyperplasia and synchronous or metachronous endometrial carcinoma (n =
      15); group 3, patients with endometrial carcinoma only (n = 18). Overall, 13 of
      33 endometrial carcinomas (39%) displayed high-level microsatellite instability.
      None of the complex atypical hyperplasias in group 1 had high-level
      microsatellite instability or loss of hMLH1/hMSH2 protein expression. In group 2
      patients, 33% of complex atypical hyperplasias and 53% of endometrial carcinomas
      had high-level microsatellite instability. Loss of hMSH2 protein expression was
      found in six endometrial carcinoma patients, five of them with verified hMSH2
      germline mutations, including four patients with high-level microsatellite
      instability in complex atypical hyperplasia. Among group 3 patients, 28% of
      endometrial carcinomas displayed high-level microsatellite instability; three of
      those five endometrial carcinomas were from patients with multiple extrauterine
      hereditary nonpolyposis colorectal cancer-associated tumors. We conclude that
      young women (< or =50 years of age) with concurrent complex atypical hyperplasia
      and multiple hereditary nonpolyposis colorectal cancer-associated carcinomas are
      at risk of developing high-level microsatellite instability endometrial
      carcinoma. Combined microsatellite instability and immunohistochemistry analysis
      allows the identification of a high proportion of hereditary nonpolyposis
      colorectal cancer patients among young women with endometrial carcinoma and
      complex atypical hyperplasia. All complex atypical hyperplasias with high-level
      microsatellite instability progressed to endometrial carcinoma. Only one third of
      the complex atypical hyperplasias with microsatellite stability progressed to
      high-level microsatellite instability endometrial carcinoma, while seven complex
      atypical hyperplasias progressed to microsatellite stability endometrial
      carcinoma. Microsatellite analysis of complex atypical hyperplasia in young
      patients may therefore be a useful prognostic marker for predicting possible
      progression to high-level microsatellite instability endometrial carcinomas.

PMID- 14668546
TI  - Incidental findings in uterine prolapse specimen: frequency and implications.
AB  - Uterine prolapse is a benign and common condition, especially in older women. In
      this study, we investigated the frequency and implications of incidental findings
      in uteri removed for prolapse. We found a high frequency of incidental findings
      that was greater than previously reported and a correlation between the
      occurrence of leiomyomata and adenomyosis. As long as all grossly visible lesions
      are sampled, two routine sections were found to be sufficient to identify all
      significant lesions.

PMID- 14668547
TI  - Histopathology, FIGO stage, and BRCA mutation status of ovarian cancers from the
      Gilda Radner Familial Ovarian Cancer Registry.
AB  - Studies of the histopathology of ovarian cancer arising in patients with germline
      mutations in BRCA1 or BRCA2 have shown inconsistent findings. We analyzed the
      large number of tumors from women enrolled in the Gilda Radner Familial Ovarian
      Cancer Registry for correlations between histopathology and BRCA mutation status.
      Histopathology slides and reports were reviewed for histology, grade, and stage
      for cancers of the ovary or peritoneum in 220 women from 126 Gilda Radner
      Familial Ovarian Cancer Registry families. At least one affected member of each
      family was analyzed for mutations in the BRCA1 and BRCA2 genes, and tumors from
      mutation-positive families were compared with those from mutation-negative
      families. Of 70 patients from 38 BRCA1-positive families, 69 had epithelial
      ovarian carcinoma and one had a dysgerminoma. Fifteen of 16 patients from nine
      BRCA2-positive families had epithelial ovarian cancer, and one had a primary
      peritoneal cancer. Of 134 patients from 79 BRCA-negative families, 118 had
      epithelial ovarian carcinoma, 11 had ovarian borderline tumors, three had
      nonepithelial tumors, and two had primary peritoneal carcinoma. There were fewer
      grade 1 (p < 0.001) and stage I (p = 0.005) cancers in patients from BRCA
      positive families than in patients from BRCA-negative families. Neither mucinous
      nor borderline tumors were found in the BRCA-positive families. In conclusion,
      ovarian cancers arising in women from BRCA-positive families are more likely to
      be high-grade and have extraovarian spread than tumors arising in women from BRCA
      negative families. Borderline and mucinous tumors do not appear to be part of the
      phenotype of families with germline mutations in the BRCA genes.

PMID- 14668548
TI  - Atypical epithelial proliferation in fallopian tubes in prophylactic salpingo
      oophorectomy specimens from BRCA1 and BRCA2 germline mutation carriers.
AB  - Although growing numbers of tubal carcinomas in carriers of BRCA1 and BRCA2
      germline mutations have been reported, very little is known about the nature and
      frequency of their possible precursor lesions. The aim of this study is to
      investigate the occurrence of atypical proliferative tubal lesions in grossly
      normal fallopian tubes from 26 women with BRCA1 and BRCA2 germline mutations who
      underwent prophylactic salpingo-oophorectomy and whose ovaries were
      histologically negative for carcinoma. Fallopian tubes from 49 women who had
      undergone hysterectomy with salpingo-oophorectomy for uterine leiomyoma served as
      controls. In the 22 BRCA1-mutated women, there were two in situ carcinomas and
      two atypical hyperplasias of the tubal epithelium. The tubes of the BRCA2-mutated
      women and of the 49 control women did not show any atypical proliferation. The
      frequency of proliferative lesions of the tubal epithelium, including in situ
      carcinoma, appears to be increased in BRCA1 mutation carriers. Removal and
      thorough examination of the fallopian tubes at the time of surgical prophylaxis
      for ovarian cancer is therefore recommended.

PMID- 14668549
TI  - The histologic type and stage distribution of ovarian carcinomas of surface
      epithelial origin.
AB  - Advances over the past decade suggest a need to reassess the distribution of
      ovarian surface epithelial tumors. A series of 220 consecutive invasive ovarian
      carcinomas, including carcinosarcomas and peritoneal carcinomas, was reviewed.
      Notable findings include: 7% of tumors were carcinosarcomas; 22% of cases of
      peritoneal serous carcinomatosis were of peritoneal origin; <3% of cases were
      mucinous carcinomas; and only one malignant Brenner tumor (0.5%) and no pure
      transitional cell carcinomas were identified. If peritoneal carcinomas,
      carcinosarcomas, and mixed carcinomas with a serous component are combined with
      serous carcinomas, this group accounts for 78% of all cases and 87% of advanced
      stage cases, suggesting a greater uniformity to epithelial ovarian cancer than
      previously appreciated.

PMID- 14668550
TI  - Signet-ring stromal tumor of the ovary: clinicopathologic analysis and comparison
      with Krukenberg tumor.
AB  - Signet-ring stromal tumor is a rare ovarian neoplasm that can mimic Krukenberg
      tumor because of the presence of signet-ring cells in both tumors. The
      clinicopathologic features of three signet-ring stromal tumors, one of which has
      been previously reported, were analyzed and compared with 10 Krukenberg tumors.
      Patients with signet-ring stromal tumor ranged in age from 34 to 41 years (mean:
      36.7 years). All signet-ring stromal tumors were unilateral and stage IA, whereas
      60% and 40% of Krukenberg tumors were bilateral or associated with extraovarian
      tumor, respectively. The signet-ring stromal tumors were devoid of epithelial
      differentiation (glands, nests, cords), whereas all of the Krukenberg tumors
      contained these epithelial structures at least focally. In contrast to signet
      ring stromal tumors, the signet-ring cells of Krukenberg tumors were positive for
      periodic acid-Schiff with diastase and cytokeratins but negative for vimentin.
      The patients with signet-ring stromal tumors were alive without disease at follow
      up interval of 1 month to 17.4 years (mean: 7.4 years). In summary, signet-ring
      stromal tumor is a rare, benign, ovarian tumor that may be mistaken for
      Krukenberg tumor. Although the combination of operative and histopathologic
      findings allow their distinction, histochemical and immunohistochemical stains
      may also be useful.

PMID- 14668551
TI  - The value of Cdx2 immunostaining in differentiating primary ovarian carcinomas
      from colonic carcinomas metastatic to the ovaries.
AB  - Histologic differentiation of primary ovarian carcinoma from colonic carcinoma
      metastatic to the ovary may be difficult. Cytokeratin 7 (CK7) and cytokeratin 20
      (CK20) immunostaining is usually used, but these markers lack specificity for
      ovarian and intestinal epithelium, and overlapping results have been reported.
      Cdx2 is a transcription factor whose expression in normal tissues is limited to
      the intestinal epithelium. It is also expressed in the vast majority of colonic
      carcinomas and in a sizeable proportion of cases of gastric, pancreatobiliary,
      and ovarian mucinous carcinomas. We evaluated Cdx2, CK7, and CK20 expression in
      50 ovarian carcinomas (15 serous, 20 mucinous, and 15 endometrioid), 15 colonic
      carcinomas metastatic to the ovaries, and 20 primary colonic carcinomas. The
      extent (1-25%/1+, 26-75%/2+, >75%/3+) and intensity (weak/1+, strong/2+) of
      staining were recorded semiquantitatively. All primary and metastatic colonic
      carcinomas had diffuse (3+) strong Cdx2 reactivity. All serous and endometrioid
      tumors were Cdx2 negative, whereas mucinous carcinomas had 1+ or 2+
      immunoreactivity. All ovarian carcinomas had strong diffuse CK7 staining, whereas
      all colonic carcinomas were negative for CK7. CK20 stained diffusely and strongly
      all primary and metastatic colonic carcinomas and was 1+ or 2+ in all mucinous
      carcinomas, in 67% of serous carcinomas, and in 33% of endometrioid carcinomas.
      In conclusion, 1) Cdx2 is a highly sensitive (100%) marker for colonic carcinoma
      metastatic to the ovary; 2) Cdx2 is more specific than CK20 as it is not
      expressed by serous and endometrioid carcinomas; and 3) a limited panel of Cdx2
      and CK7 helps in distinguishing colonic carcinomas metastatic to the ovaries
      (Cdx2+/CK7-) from primary ovarian serous (Cdx2-/CK7+), endometrioid (Cdx2-/CK7+),
      and mucinous (Cdx2+/CK7+) carcinomas.

PMID- 14668552
TI  - Hepatocyte paraffin 1 antibody does not distinguish primary ovarian tumors with
      hepatoid differentiation from metastatic hepatocellular carcinoma.
AB  - Anti-hepatocyte antibody, hepatocyte paraffin 1, is a monoclonal antibody that is
      highly specific for normal and neoplastic hepatocytes and that can differentiate
      hepatocytic from nonhepatocytic tumors. This marker has been rarely studied in
      extra-hepatic tumors and to our knowledge has not been investigated in ovarian
      tumors with hepatoid differentiation. We studied hepatocyte paraffin 1
      immunoreactivity in a series of ovarian hepatoid carcinomas, ovarian hepatoid
      yolk sac tumors (YSTs), and hepatocellular carcinomas metastatic to the ovary to
      assess the potential utility of hepatocyte paraffin 1 in differential diagnosis.
      Hepatocyte paraffin 1 positivity was seen in three of seven ovarian hepatoid
      carcinomas, five of eight hepatoid yolk sac tumors, and six of eight metastatic
      hepatocellular carcinomas. The extent of positivity ranged from <25% to >50% of
      the tumor cells. There was strong coarsely granular cytoplasmic staining in all
      three tumor types without a distinctive staining pattern in any group. The degree
      of hepatic differentiation correlated with hepatocyte paraffin 1 positivity in
      the three groups: 83% of the well differentiated tumors, 50% of the moderately
      differentiated tumors, and none of the poorly differentiated tumors were
      positive. All ovarian hepatoid carcinomas were either immunoreactive for alpha
      fetoprotein or had an elevated serum alpha-fetoprotein level; more than half of
      these tumors were hepatocyte paraffin 1 negative. All but one hepatocyte paraffin
      1 negative hepatoid yolk sac tumor and ovarian hepatocellular carcinoma were also
      negative for alpha-fetoprotein. In conclusion, hepatocyte paraffin 1 is positive
      in primary ovarian tumors with hepatoid differentiation, with the degree of
      hepatocyte paraffin 1 positivity correlating with the degree of hepatoid
      differentiation. Hepatocyte paraffin 1, however, is not useful in distinguishing
      metastatic hepatocellular carcinoma from primary ovarian hepatoid carcinoma or
      hepatoid yolk sac tumor.

PMID- 14668553
TI  - Ischemic fasciitis: an unusual vulvovaginal spindle cell lesion.
AB  - Ischemic fasciitis is a benign reactive lesion that most commonly occurs in
      elderly, immobile patients in weight-bearing areas that are subject to
      intermittent ischemia with subsequent tissue breakdown and regenerative changes.
      The lesion can be clinically and pathologically mistaken for malignancy. Here we
      describe the first reported case of ischemic fasciitis of the vulvovaginal region
      in a 20-year-old paraplegic woman who presented with a clinically suspicious
      vulvar swelling. Histologic examination showed surface ulceration and underlying
      fibrinoid necrosis with surrounding reactive atypical fibroblast-like cells and
      small blood vessels, the characteristic histologic features of ischemic
      fasciitis.

PMID- 14668554
TI  - Spindle cell vulvar hemangiomatosis associated with enchondromatosis: a rare
      variant of Maffucci's syndrome.
AB  - Spindle cell hemangioma is a rare vascular tumor that most frequently involves
      the distal extremities, especially the hand. We report a case of spindle cell
      hemangiomatosis of the vulva in an 18-year-old woman with Maffucci's syndrome,
      the first report of such a case, to the best of our knowledge. The vascular
      lesions, present from the age of 2, were located in the right olecranon, the
      third left toe, and the vulva. Spindle cell hemangiomas are either benign
      neoplasms or hamartomatous malformations.

PMID- 14668555
TI  - Skene's gland adenocarcinoma resembling prostatic adenocarcinoma.
AB  - An 88-year-old woman presented with gross hematuria and a 3-cm periurethral mass.
      Biopsy revealed an adenocarcinoma resembling prostatic adenocarcinoma; the tumor
      cells were positive for keratin and prostate-specific antigen. The serum level of
      prostate-specific antigen was elevated; the carcinoembryonic antigen and CA-125
      serum levels were normal. One year after external beam radiotherapy, the patient
      is without evidence of disease. This is the sixth case of a urethral prostatic
      type adenocarcinoma, tumors that are most likely of Skene's gland origin.

PMID- 14668556
TI  - Recurrent verruciform xanthoma of the vulva.
AB  - Verruciform xanthoma is a rare, benign, mucocutaneous, nondestructive lesion
      characterized by proliferation of non-Langerhans lipid-rich histiocytes. We
      describe the clinical and pathologic findings in a 30-year-old female with
      recurrent verruciform xanthoma of the vulva 8 years after initial therapy. The
      differential diagnosis includes seborrheic keratosis, verruca simplex, condyloma
      acuminatum, granular cell myoblastoma, vulvar intraepithelial neoplasia, bowenoid
      papulosis, erythroplasia of Queyrat, and verrucous carcinoma.

PMID- 14668557
TI  - Sarcoma botryoides of the uterine cervix in a 46-year-old woman: case report and
      literature review.
AB  - Sarcoma botryoides, which usually occurs in the vagina in childhood, is rare in
      the female reproductive tract of adult women, especially those over the age of
      40. We present a case of sarcoma botryoides of the uterine cervix that was an
      incidental finding in a 46-year-old woman. The tumor formed a grape-like cervical
      polyp that was locally excised, but rapidly recurred. Total abdominal
      hysterectomy and bilateral salpingo-oophorectomy were performed. The myxoid tumor
      had a cambium layer and was composed of spindle-shaped myoblastic cells without
      apparent cross-striations. The tumor cells were immunoreactive for MyoD1 and
      myogenin. Postoperative chemotherapy (vincristine and actinomycin D) was given
      according to the Intergroup Rhabdomyosarcoma Study protocol, and the patient was
      alive without recurrence 45 months postoperatively. This is the only the fourth
      case reported in detail of a sarcoma botryoides of the uterine cervix in a
      patient over the age of 40.

PMID- 14668558
TI  - History of gynecological pathology. XV. Dr. Carl Arnold Ruge.

PMID- 14668559
TI  - Stromal reaction is a feature of diffusely infiltrating endometrial
      adenocarcinoma.

PMID- 14668560
TI  - Asynchronism of the recovery of baroreflex sensitivity, blood pressure, and
      consciousness from anesthesia in rats.
AB  - Anesthesia inhibits arterial baroreflex functions such as baroreflex sensitivity
      (BRS). The main objective of the present study was to determine the time course
      of BRS recovery from anesthesia and to determine whether BRS recovery is
      synchronous with the recovery of consciousness and blood pressure (BP).
      Experiments were performed in male Sprague-Dawley rats using different commonly
      used anesthetics at routine doses through intraperitoneal administration: (1)
      diazepam/ketamine, a mixture of diazepam (5 mg/kg) and ketamine (50 mg/kg); (2)
      chloral hydrate (0.3 g/kg); (3) sodium pentobarbital (30 mg/kg); and (4) urethane
      (1.0 g/kg). The anesthetic state, evaluated by algesthesia and cornea reflex, was
      maintained for 1-2.5 hours. The BRS, assessed by intravenous injection of
      phenylephrine, was inhibited rapidly and dramatically, with maximum depressions
      of 51%-80%. The BRS recovery time was approximately 5 hours for
      diazepam/ketamine, chloral hydrate, and pentobarbital, but more than 24 hours for
      urethane. Compared with BRS inhibition, BP reduction was less pronounced by 8%
      (not significant) for diazepam/ketamine and by 12%-30% for the others. The BP
      recovery time was approximately 2 hours, with the exception of chloral hydrate
      (>6 hours). In conclusion, after anesthesia, BRS inhibition is more obvious than
      BP reduction, and the recovery of BRS lags behind the recovery of consciousness
      or BP.

PMID- 14668561
TI  - Glucocorticoids decrease GTP cyclohydrolase and tetrahydrobiopterin-dependent
      vasorelaxation through glucocorticoid receptors.
AB  - Excess glucocorticoids result in decreased aortic dilation and expression of
      guanosine triphosphate (GTP) cyclohydrolase 1 (GTPCH1) messenger RNA (mRNA), the
      rate-limiting enzyme in the production of the nitric oxide synthase (NOS)
      cofactor tetrahydrobiopterin (BH4). It was hypothesized that this response is a
      genomic effect mediated through the glucocorticoid receptor (GR). Endothelium
      intact rat aortas were incubated with dexamethasone (DEX; 1.3 x 10(-6) M) or
      vehicle for 2 or 6 hours and isometric force generation was measured. Maximum
      acetylcholine-induced relaxation in DEX-2hr aortas was not different compared
      with control values; however, acetylcholine-induced relaxations in DEX-6hr aortas
      were significantly decreased. Coincubation with sepiapterin (10(-4) M), which
      produces BH4 via a salvage pathway, restored relaxation in DEX-6hr aortas to that
      of controls. Coincubation with the GR antagonist mifepristone (10(-6) M)
      completely blocked the DEX-induced decrease in relaxation. Spironolactone (10(-5)
      M), a mineralocorticoid receptor antagonist, had no effect. GTPCH1 mRNA
      expression was significantly decreased in DEX-6hr aortas compared with control
      values. This was blocked by mifepristone; however, spironolactone and
      cycloheximide did not prevent the decrease of GTPCH1 by DEX. These results
      support the hypothesis that GTPCH1 downregulation by glucocorticoids is mediated
      through the GR and contributes to reduced endothelium-dependent relaxation.

PMID- 14668562
TI  - Different AT1 receptor subtypes at pre- and postjunctional sites: AT1A versus
      AT1B receptors.
AB  - Angiotensin (AT) II is known to enhance responses to electrical field stimulation
      (EFS) via AT1 receptors located on sympathetic nerve terminals. Differences in
      potency exist between AT1 receptor antagonists regarding the inhibition of the
      prejunctional and postjunctional AT1 receptors. It is hypothesized that
      prejunctional AT1 receptors might belong to the AT1B receptor subtype.
      Accordingly, the authors investigated whether AT1B receptor inhibition by high
      concentrations of PD123319 could suppress ATII-augmented noradrenergic
      transmission (prejunctional) in the rabbit thoracic aorta by means of a
      noradrenaline spillover model. Additionally, the influence of PD123319 on ATII
      enhanced constrictor responses to electrical field stimulation was investigated
      in the isolated rabbit mesenteric artery. Furthermore, the authors investigated
      whether PD123319 could influence the constrictor responses (postjunctional) to
      ATII in both preparations. In the thoracic aorta, ATII (10 nM) caused a
      significant enhancement of EFS-evoked [3H]-noradrenaline release by a factor of
      2.0 +/- 0.1. This reinforcement could be inhibited by PD123319 (0.1, 1, and 10
      microM). The constrictor response to ATII was unaffected by PD123319. In the
      mesenteric artery, ATII (0.5 nM) caused a significant enhancement of constrictor
      responses to EFS by factors of 2.9 +/- 0.3, 2.3 +/- 0.3, and 1.6 +/- 0.1 at 1, 2,
      and 4 Hz, respectively. This enhancement could be attenuated by PD123319 (1 and
      10 microM). The constrictor response to ATII was unaffected by PD123319. It is
      concluded that the prejunctional AT1 receptors belong to the AT1B subtype whereas
      postjunctional AT1 receptors do not.

PMID- 14668563
TI  - Evaluation of luminal endothelin-converting enzyme activity in the pulmonary and
      coronary circulations.
AB  - The endothelin-converting enzymes are distributed on both the surface of the
      endothelium and intracellularly. Whether circulating big-endothelin-1 can be
      hydrolyzed in plasma by lumen-bound endothelin-converting enzymes is unknown. The
      lung is the major site for hydrolysis of angiotensin-I to angiotensin-II by the
      angiotensin-converting enzyme; because of its high content in endothelin
      converting enzymes, we hypothesized that the lung could similarly hydrolyze
      circulating big-endothelin-1. Since big-endothelin-1 produced by the lung can
      modulate coronary vascular tone, the heart may also have the capacity to
      hydrolyze circulating big-endothelin-1. Isolated lungs and hearts from Sprague
      Dawley rats were perfused at 10 mL/min. Clearance of trace doses of human I125big
      endothelin-1 was quantified using the indicator-dilution curves technique with
      labeled albumin as a vascular reference. Single-pass hydrolysis was assessed by
      bolus injection of human big-endothelin-1 (24 fmol) followed by serial ELISA
      determinations of big-endothelin-1 and endothelin-1 levels in effluent samples.
      To exclude possible uptake of produced endothelin-1, 10(-6) M BQ788 was added to
      the perfusate. The injections had no effect on perfusion pressures. There was no
      detectable clearance of I125big-endothelin-1 in the lung; however the heart
      extracted 14 +/- 1% of the injected tracer. There was no detectable big
      endothelin-1 hydrolysis in the pulmonary as well as in the coronary circulations.
      The pulmonary circulation does not clear or hydrolyze circulating big-endothelin
      1 suggesting that endothelin-converting enzymes are predominantly used for
      intracellular and/or abluminal conversion of locally produced big-endothelin-1.
      Mild coronary uptake of big-endothelin-1 suggests that this circulating peptide
      could modulate coronary vascular tone.

PMID- 14668564
TI  - Age-related changes of vitamin A status.
AB  - Ageing is an independent risk factor for the development of cardiovascular
      disease. The ageing process is known to be associated with increased oxidative
      stress and an increased risk for cardiovascular and other diseases, such as
      cancer. To delay this process, therapeutic strategies involving the use of
      naturally occurring antioxidants, such as vitamin A, have gained considerable
      interest. Therefore, we wanted to investigate in a model of mammalian ageing
      whether changes in tissue and plasma levels of vitamin A occur with increasing
      age. This would constitute a prime rationale for its dietary supplementation.
      Experiments were performed in three different age groups (4-6 months old, 19
      months old, 32-35 months old) of F1 (F344 x BN) healthy male rats that were fed a
      normal diet without any additional supplementation. Vitamin A and carotenoids in
      plasma and major organs were measured by reverse-phase high-performance liquid
      chromatography. In 3-year-old rats, vitamin A levels were found to be decreased
      in plasma (P < 0.0001) as compared with young and middle-aged animals. However,
      they were markedly increased in the main storage organ (ie, the liver) (P < 0.01
      0.0001), and also in the aortic vessel wall. They were undetectable in the heart,
      irrespective of age. Increased tissue levels of vitamin A, especially in the
      vasculature, may be part of an age-associated self-regulatory process of
      adaptation, possibly as a counter-regulation against oxidative tissue damage.
      Based upon the assumption that in elderly humans, as in our animal model, a
      similar demand-regulated mechanism may work independently of additional dietary
      vitamin A supplementation, one may question the strategy of large clinical
      interventional trials using vitamin A or its derivatives beyond normal dietary
      intake.

PMID- 14668565
TI  - Inhibition of neointimal proliferation in balloon-injured arteries using non
      anticoagulant heparin-carrying polystyrene.
AB  - Non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) has a higher activity
      to inhibit proliferation and migration of smooth muscle cells (SMCs) than heparin
      (Hep), periodate-oxidized (IO4-) Hep, and periodate-oxidized alkaline-degraded
      low molecular weight (IO4-LMW-) Hep. Less than 10 microg/ml of NAC-HCPS
      significantly inhibited the proliferation and migration of SMCs in vitro, while
      over 10-fold higher concentrations of Hep, IO4-Hep, and IO4-LMW-Hep were required
      to obtain the same inhibition. On the other hand, neointimal growth (intimal
      cross-section area and intimal cross-section area/medial cross-section area
      ratio) in vivo following vascular injury 28 days after balloon denudation in a
      rat carotid artery was substantially inhibited with high dose of intravenous
      administration (total 30 mg) of respectively IO4-Hep, IO4-LMW-Hep, and NAC-HCPS.
      A low-dose (total 10 mg) administration of IO4-Hep and IO4-LMW-Hep did not
      prevent the neointimal growth when compared with the control; only NAC-HCPS
      (total 10 mg) was able to significantly inhibit the neointimal. Thus, NAC-HCPS
      has a more-than 10-fold larger activity to inhibit SMC activities such as
      proliferation and migration in vitro, when comparing with Hep, IO4-Hep, and IO4
      LMW-Hep; NAC-HCPS also prevents neointimal growth in vivo at lower doses.

PMID- 14668566
TI  - Coxsackievirus B3 infection compromises endothelial-dependent vasodilation of
      coronary resistance arteries.
AB  - The mechanisms of coronary artery dysfunction in coxsackievirus B3 (CVB3)
      mediated viral myocarditis are poorly understood. We used pressure myography of
      mouse septal coronary arteries to determine the early and late effects of CVB3
      infection on vascular function. Male CD-1 mice (age 6-7 weeks) were infected with
      CVB3 (1.75 x 10(10) pfu, i.p.). Control mice were injected with PBS. Mice were
      killed at 3, 7, and 42 days post infection, and the ventricular septal artery was
      dissected and mounted on a pressure myograph. Pressure-induced myogenic tone was
      similar in CVB3-infected and sham-infected mice at 3 and 7 days post infection.
      However, at 42 days post infection constriction of septal arteries to pressures
      equal to or less than 60 mm Hg was enhanced in CVB3-infected mice compared with
      sham controls. Agonist-induced vasodilation, as assessed by response to
      acetylcholine (1 nM-3 microM), was unaltered at early time points (days 3 and 7)
      in CVB3-infected mice. At later time points (day 42), there was a significant
      decrease in ACh-induced vasodilation in CVB3-infected mice. Bosentan, an ET-1
      (ETA and ETB) receptor antagonist, did not completely ameliorate the reduced ACh
      induced vasodilation in 42-day infected mice, indicating that ET-1 does not
      contribute to vascular dysfunction. Smooth muscle function, as measured by
      constriction to KCl or dilation to sodium nitroprusside, was unchanged in
      infected mice at early and late time points. Immunohistochemistry and ET-1
      immunoassay were then performed to assess ET-1 levels in CVB3- and sham-infected
      hearts. There were no differences in ET-1 protein localization or levels at 42
      days post infection in sham- and CVB3-infected animals. Finally, in situ
      hybridization and TUNEL staining were performed to assess viral localization and
      cell death in CVB3-infected hearts. There was no detectable CVB3 or TUNEL
      positivity in the endothelium of coronary arteries. Therefore, late impairment of
      endothelial-dependent vasorelaxation of coronary resistance vessels in CVB3
      induced myocarditis does not appear to involve altered ET-1 expression but may be
      secondary to decreased stimulated NO secretion by the endothelium.

PMID- 14668567
TI  - Relative contribution of estrogen withdrawal and gonadotropins increase secondary
      to ovariectomy on prostaglandin generation in mesenteric microvessels.
AB  - Recent studies have established that ovariectomy impairs endothelial function,
      partially by increasing vasoconstrictor prostaglandins generation. Because
      ovariectomy causes concomitant lack of estrogen and increase of gonadotropins
      (ie, LH and FSH), in this study we explored the relative role of estrogen and
      LH/FSH in modulating vasoconstrictor prostaglandins generation in mesenteric
      arteriolar bed of SHR. Endothelium-dependent relaxation to acetylcholine (ACh)
      and bradykinin (Bk) was markedly reduced in ovariectomized (OVX) compared with
      SHR in physiological estrus (OE). Estrogen replacement (OVX + E), but not the
      decrease in LH/FSH levels with leuprolide (OVX + Leu), corrected the altered
      vasorelaxation response in OVX. Treatment of mesenteries with diclofenac,
      prostaglandin-H synthase (PGHS) inhibitor, significantly enhanced the relaxing
      response in arteries from OVX and OVX + Leu, but not those from OE, indicating
      that a PGHS-derived vasoconstrictor has modified the endothelium-dependent
      response during estrogen but not LH/FSH deprivation. Confirming these data, in
      response to exogenous arachidonic acid, whereas arteries from OVX and OVX + Leu
      exhibited a marked and similar vasoconstrictor response, the arteries from OE and
      OVX + E rats exhibited a slight vasodilation. We also demonstrated by RT-PCR that
      ovariectomy significantly increased PGHS-2 but not PGHS-1 mRNA expression in
      comparison to OE. The PGHS-2 overexpression in OVX was corrected by estrogen
      replacement, but not by the reduction of LH/FSH levels. Altogether these data
      strongly support a role for hypoestrogenism rather than LH/FSH enhancement,
      associated with the removal of ovaries, in the increase of vasoconstrictor
      prostaglandins, possibly by a mechanism involving PGHS-2 overexpression.

PMID- 14668568
TI  - Twice-daily administration of a long-acting angiotensin-converting enzyme
      inhibitor has greater effects on neurohumoral factors than a once-daily regimen
      in patients with chronic congestive heart failure.
AB  - Although many clinical trials have evaluated the use of long-acting angiotensin
      converting enzyme (ACE) inhibitors in patients with chronic congestive heart
      failure (CHF), there are no data regarding whether a once-daily or twice-daily
      regimen is preferable with respect to effects on the neuroendocrine system. To
      address this issue, the authors evaluated the comparative effects of the
      administration schedule on neurohumoral factors and autonomic nervous activity in
      patients with CHF. Thirty-two patients with mild compensated CHF received
      lisinopril (5-20 mg/d) orally either once a day (n = 17) or twice a day (n = 15)
      for more than 3 months. After this initial therapy, patients receiving a once
      daily regimen switched to a twice-daily regimen and vice-versa, and patients were
      followed for an additional 3 months. Neurohumoral factors and the coefficient of
      variance in the electrocardiographic R-R interval (CVRR) were measured.
      Hemodynamic parameters, renal function, plasma concentrations of brain
      natriuretic peptide and aldosterone, and CVRR did not differ between the two
      regimens. However, the plasma concentration of norepinephrine was significantly
      lower, and plasma renin activity tended to be lower with the twice-daily regimen.
      These findings suggest that twice-daily administration of long-acting ACE
      inhibitors may have better effects on the neuroendocrine system than a once-daily
      regimen in patients with mild CHF.

PMID- 14668569
TI  - Effects of immunoglobulin upon murine myocarditis caused by influenza A virus:
      superiority of intact type to F(ab')2 type.
AB  - Influenza viruses play the largest role in the worldwide epidemiology of
      infectious diseases. Management of some inflammatory disease (eg, Kawasaki
      disease) with immunoglobulin has been demonstrated to be effective. We examined
      the effects of intact type and F(ab')2 type of immunoglobulin preparations upon
      murine influenza A virus myocarditis in mice. In vitro study showed that intact
      type and F(ab')2 type of immunoglobulin preparations exhibit antiviral activities
      against many substrains of influenza virus and other cardiotropic viruses. Dose
      dependent suppression of an influenza A virus (NWS) was demonstrated by
      management with both intact immunoglobulin and F(ab')2 fragments of
      immunoglobulin. The dose inhibiting 50% of plaques was the same between intact
      type and F(ab')2 type (both 0.0002 mg/dl). Intact immunoglobulin, but not F(ab')2
      fragments of immunoglobulin, suppressed serum macrophage inflammatory protein-2
      (MIP-2) productions in influenza A virus-infected macrophages in vitro, which is
      a murine counterpart of interleukin-8. This suppression of MIP-2 production by
      intact immunoglobulin treatment was blocked by a specific Fc receptor (Fc gamma
      III/II receptor) antibody pretreatment. Intact immunoglobulin or F(ab')2
      fragments of immunoglobulin were administered to virus-inoculated A/J mice
      intraperitoneally daily, starting simultaneously with virus inoculation
      (Experiment I) and 2 days after the virus inoculation (Experiment II), until 10
      days after virus inoculation. In Experiment I, survival was higher in treated
      than in control mice; intact type and F(ab')2 type immunoglobulins administration
      completely suppressed the development of myocarditis. In Experiment II, survival
      rate was significantly higher and myocarditis was less severe in intact
      immunoglobulin-treated mice, but not in F(ab')2 fragments-treated mice compared
      with untreated mice. Serum neutralizing antibody titers in treated mice were
      significantly higher compared with untreated mice in Experiments I and II. In
      addition, serum MIP-2 concentrations in intact immunoglobulin-treated mice, but
      not in F(ab')2 fragments-treated mice, were lower compared with untreated mice in
      Experiment II. Immunoglobulin therapy suppresses influenza A virus myocarditis by
      increasing neutralizing antibody titers and the suppression of myocardial virus
      activities. From the standpoint of suppression of MIP-2 concentrations, intact
      type is superior to F(ab')2 type. Thus, immunoglobulin treatment may be promising
      for prevention of influenza virus myocarditis.

PMID- 14668570
TI  - Effect of morning and bedtime dosing with cilnidipine on blood pressure, heart
      rate, and sympathetic nervous activity in essential hypertensive patients.
AB  - Cilnidipine has a blocking action against N-type calcium channels as well as L
      type calcium channels. We studied the effect of morning and bedtime dosing on
      circadian variation of blood pressure (BP), heart rate (HR), and activity of the
      autonomic nervous system, using an open randomized crossover study in 13
      essential hypertensive patients. An automated device allowed 24-hour monitoring
      of ambulatory BP and HR and the power spectrum of the R-R interval, at the
      observation period, the morning dosing regimen, and the bedtime dosing regimen.
      Morning dosing and bedtime dosing with cilnidipine reduced the average systolic
      BP over 24 hours, during daytime, and during nighttime. The average HR and the
      average LF/HF ratio over 24 hours, during daytime, and during nighttime, were
      similar for the three periods. Both morning and bedtime dosing reduced the
      maximum systolic BP in the early morning and suppressed the morning rise of BP,
      which were accompanied by partial inhibition of the increase in LF/HF ratio. Our
      results show that cilnidipine administered once daily is an efficient
      antihypertensive drug regardless of the time of dosing, without reflex
      tachycardia and increase in sympathetic nervous activity, and with partial
      inhibition of the morning activation of the sympathetic nervous system.

PMID- 14668571
TI  - In vitro effects of clopidogrel on the platelet-subendothelium interaction,
      platelet thromboxane and endothelial prostacyclin production, and nitric oxide
      synthesis.
AB  - Clopidogrel is an antiplatelet drug that belongs to the group of thienopyridines.
      Because of its main mechanism of action most studies of clopidogrel have centered
      on the platelet ADP pathway. The aim of the present study was to compare the
      effects of clopidogrel, ticlopidine, and aspirin, on platelet activation by
      collagen (the main inducer of platelet activation in vivo), prostanoid, and NO
      production, and the effects on blood perfusion experiments. Clopidogrel inhibited
      platelet aggregation induced in whole blood by collagen and TxB2 production to a
      greater extent than did ticlopidine. Prostacyclin synthesis did not change after
      incubation with thienopyridines, whereas aspirin inhibited synthesis in a dose
      dependent manner. Thienopyridines increased NO production to a greater extent
      than did aspirin. All three drugs impaired the platelet-subendothelium
      interaction under flow conditions. With thienopyridines, the presence of
      endothelium did not modify the percentage of the surface coated by platelets.

PMID- 14668572
TI  - Pharmacologically distinct intracellular calcium pools regulate tonic and
      oscillatory responses in porcine thoracic duct.
AB  - The present study investigated the mechanisms by which the thromboxane A2 mimetic
      U46619 can elicit phasic and tonic contractions in the pig thoracic duct, whereas
      other agonists like 5-hydroxytryptamine (5-HT) produce tonic contractions only.
      Tonic contractions in response to either agonist were abolished by the l-type
      voltage-operated calcium channel (VOCC) inhibitor nifedipine, the store-operated
      calcium channel inhibitor SKF 96365, the calcium-sensitive chloride channel
      (ClCa) inhibitor niflumic acid, and by removal of extracellular Cl-. Superimposed
      phasic responses to U46619 were abolished by only nifedipine. Inhibitors of K+
      channels did not prevent phasic contractions to U46619. The IP3 receptor
      antagonist 2-APB attenuated tonic contractions only, whereas ryanodine and
      removal of extracellular Na+ selectively abolished phasic contractions to U46619.
      Therefore, selective initiation of phasic contractions by U46619 appears to
      depend on intracellular Ca2+ from a ryanodine-sensitive store that causes
      depolarization via Na+/Ca2+ exchange, whereas tonic contractions to U46619 and 5
      HT are mediated primarily by release of IP3-mobilized intracellular Ca2+ that
      subsequently causes ClCa opening, membrane depolarization, and Ca2+ entry via l
      type VOCC.

PMID- 14668573
TI  - Sepiapterin decreases vasorelaxation in nitric oxide synthase inhibition-induced
      hypertension.
AB  - Exogenous BH4 (tetrahydrobiopterin) has been shown to improve endothelial
      function in cardiovascular disease; however, in the presence of elevated
      superoxide levels and decreased nitric oxide synthase (NOS) activity, BH4 may
      become autoxidized, resulting in reduced vasodilation. The authors tested the
      hypothesis that increasing BH4 will further reduce endothelium-dependent
      relaxation in aortas from rats made hypertensive by NOS inhibition. N omega-nitro
      L-arginine (L-NNA, approximately 49 mg/kg/d) was administered in the rats'
      drinking water for 4 days. Systolic blood pressures, measured by tail-cuff
      technique, were significantly increased in L-NNA-treated rats. Endothelium-intact
      aortic segments were isolated and hung in organ chambers for the measurement of
      isometric force generation. Aortas from L-NNA-treated rats had decreased
      relaxation to acetylcholine compared with controls, and this was further
      decreased after incubation with sepiapterin. Superoxide dismutase (SOD) restored
      relaxation in aortas from L-NNA-treated rats to that of control. In addition, SOD
      or ascorbic acid reversed the sepiapterin-induced decrease in relaxation in
      aortas from L-NNA treated rats. Aortas from L-NNA-treated rats in the absence and
      presence of sepiapterin, and sepiapterin-treated control aortas, had increased
      dihydroethidium staining for superoxide compared with untreated controls. These
      results support the hypothesis that sepiapterin further reduces vasodilation in
      the presence of NOS inhibition and may be caused by BH4 autoxidation.

PMID- 14668574
TI  - Effect of atropine on denervated rabbit ear blood vessels.
AB  - Surgical denervation of rabbit ear blood vessel beds was combined with the
      isolated perfused rabbit ear technique to investigate the mechanism of atropine's
      vasodilator action. Intramuscular injection of atropine 0.2 mg/kg dilated the
      denervated blood vessels in the rabbit ear like innervated ones in vivo. Atropine
      at the maximal concentration (Cmax) of 3 x 10(-6) to 3 x 10(-4) M did not
      increase effluent flow of the isolated perfused denervated rabbit ear under
      constant perfusion pressure, but chlorpromazine at a Cmax of 10(-6) M and
      acetylcholine (ACh) at 2.5 x 10(-7) M significantly increased it and
      noradrenaline (NA) at 10(-7) M significantly decreased it. Atropine at Cmax of 3
      x 10(-7) M did not affect, but at 3 x 10(-6) M it abolished the increase of the
      effluent flow induced by ACh 2.5 x 10(-7) M. Atropine at 3 x 10(-7) M did not
      affect it, but at 10(-6), 3 x 10(-6), and 10(-5) it significantly alleviated the
      decrease of effluent flow induced by NA 10(-7) M. Because the increase of
      effluent flow of rabbit ear under constant perfusion pressure reflects
      vasodilation of the ear to some extent, the study suggests that atropine has no
      direct vasodilator action; its vasodilator action is not attributed to blockade
      of M-cholinoreceptors located on the vascular wall; however, the alpha1
      adrenoceptor might be a target site mediating atropine's vasodilator action in
      vivo.

PMID- 14668575
TI  - Role of endothelin-1 and thromboxane A2 in the pulmonary hypertension induced by
      heparin-protamine interaction in anesthetized dogs.
AB  - This study aimed to study the role of thromboxane A2 (TXA2) and endothelin-1 (ET
      1) in the pulmonary hypertension induced by interaction of heparin-protamine in
      anesthetized dogs. The effect of inhaled nitric oxide (NO) was also investigated
      in this model. Dogs were anesthetized and instrumented for acquisition of mean
      arterial blood pressure, mean arterial pulmonary pressure (MPAP), and pulmonary
      pressure gradient (PPG). Cardiac index (CI), heart rate, and index of systemic
      vascular resistance were also obtained. Intravenous administration of heparin
      (500 IU/kg) 3 minutes before protamine (10 mg/kg) caused marked pulmonary
      hypertension, as evaluated by the increase in MPAP and PPG. This was accompanied
      by systemic hypotension, CI decrease, and tachycardia. Indomethacin (10 mg/kg),
      dazoxiben (10 mg/kg), or tezosentan (10-mg/kg bolus plus 10-mg/kg/h infusion)
      significantly reduced the increase in MPAP and PPG, but had no effect on the
      systemic hypotension. Similar results were obtained with inhaled NO (3 ppm).
      Plasma TXB2 levels were markedly elevated during the pulmonary hypertension, and
      this was abolished in indomethacin-treated dogs. Our study shows that interaction
      of heparin-protamine in anesthetized dogs lead to TXA2- and ET-1-mediated
      pulmonary hypertension. Drugs that interfere with the synthesis of these
      mediators as well as inhaled NO may be of beneficial value to control this
      disorder.

PMID- 14668576
TI  - Characterization of cysteinyl leukotriene receptors on human saphenous veins:
      antagonist activity of montelukast and its metabolites.
AB  - The aims of this study were to determine the cysteinyl leukotriene (CysLT)
      receptors expressed in the human saphenous vein, to examine contractile response
      to LTC4 and LTD4, to evaluate antagonist activity of montelukast, a specific
      CysLT1 receptor antagonist used in asthma, and to characterize the CysLT
      receptors involved in the contractile response. The analysis by reverse
      transcriptase polymerase chain reaction indicated that CysLT1 and CysLT2
      receptors are expressed by saphenous veins. In varicose vein rings, the potencies
      (pD2) of LTC4 and LTD4 were similar: 7.4 +/- 0.2 and 7.4 +/- 0.1, respectively.
      Pretreatment with acivicin, a gamma-glutamyl transpeptidase (gamma-GT) inhibitor,
      to prevent potential metabolism of LTC4 to LTD4, did not alter the response to
      LTC4. In nondistended vein rings from patients undergoing arterial bypass, the
      LTC4 pD2 was 7.8 +/- 0.1, and pretreatment with S-hexyl-GSH, a potent gamma-GT
      inhibitor, caused a fourfold rightward shift of the LTC4 concentration-response
      curve. In varicose and nondistended saphenous vein rings, montelukast (10(-8) and
      10(-7) M) exerted a potent activity against LTD4 and LTC4, in the presence or
      absence of gamma-GT inhibitors. In varicose vein rings, the two active
      metabolites of montelukast also exerted antagonist activities with potencies
      similar to montelukast. BAY u9773 (CysLT2 agonist/dual CysLT1/CysLT2 antagonist)
      did not cause contraction and inhibited the LTC4- and LTD4-induced contractions.
      In conclusion, human saphenous veins express CysLT1 and CysLT2 receptors, but
      only CysLT1 receptors are implicated in the contraction.

PMID- 14668577
TI  - Effect of 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors (statins) on
      tissue paraoxonase 1 and plasma platelet activating factor acetylhydrolase
      activities.
AB  - The authors investigated the effect of pravastatin and fluvastatin on paraoxonase
      1 (PON1) activity in plasma, liver, heart, and kidney, as well as on plasma
      platelet activating factor acetylhydrolase (PAF-AH) in the rat. The animals
      received pravastatin at doses of 4 and 40 mg/kg/d or fluvastatin at doses of 2 or
      20 mg/kg/d for 3 weeks. Fluvastatin (20 mg/kg/d) reduced plasma PON1 activity
      toward paraoxon and phenyl acetate by 23.6% and 17.4%, respectively. The lower
      dose of this drug as well as both doses of pravastatin had no effect on plasma
      PON1. PON1 activity toward paraoxon in the liver of rats treated with 20 mg/kg/d
      fluvastatin was 27.5% lower than in the control group, and the activity toward
      phenyl acetate was reduced by 25.4% and 35.9% in rats receiving 2 and 20 mg/kg/d
      of this drug, respectively. Fluvastatin at 2 and 20 mg/kg/d also decreased
      cardiac PON1 by 31.3% and 27.3%, respectively. Both statins reduced PON1 activity
      in the renal cortex and medulla. Statins had no effect on plasma PAF-AH. It is
      concluded that fluvastatin reduces PON1 activity more efficiently than does
      pravastatin. Reducing effect on PON1 may negatively modulate atheroprotective
      potential of statins and may contribute to differences in antiatherosclerotic
      properties of different drugs in this group.

PMID- 14668578
TI  - Effects of high ticlopidine doses on platelet function in acute coronary syndrome
      patients.
AB  - BACKGROUND: We investigated whether higher doses of ticlopidine combined with
      acetylsalicylic acid would allow a faster inhibition of platelet activation and
      aggregation in patients with acute coronary syndromes potentially undergoing
      percutaneous coronary intervention with stent placement. METHODS: Seventeen
      patients presenting with acute coronary syndromes and candidates for possible
      percutaneous coronary intervention were randomized to ticlopidine 250 mg or 500
      mg twice daily for 5 days. Platelet aggregation and activation were assessed at
      baseline before the first dose and daily for 5 days. RESULTS: After 2 days of
      treatment, 500 mg twice daily of ticlopidine produced a significantly larger
      reduction in platelet activation and aggregation than 250 mg twice daily. Mean
      platelet activation was 17.6 +/- 3.3% lower with 500 mg twice daily from days 3
      to 6 (P < or = 0.05). Mean platelet aggregation was 16.9 +/- 0.6% lower in
      patients treated with the higher dose on days 3 through 6 when compared with
      those on ticlopidine 250 mg twice daily (P < 0.05). CONCLUSIONS: A faster and
      stronger inhibition of platelet activation and aggregation is obtained when 500
      mg twice daily of ticlopidine is administered daily in combination with
      acetylsalicylic acid in patients with acute coronary syndromes.

PMID- 14668579
TI  - Site-specific intracoronary delivery of octreotide in humans: a pharmacokinetic
      study to determine dose-efficacy in restenosis prevention.
AB  - Somatostatin analogues have been shown to inhibit smooth muscle cell
      proliferation after local administration in vivo in animal models and in vitro
      using human coronary smooth muscle cell cultures. However, the optimal dosage for
      attaining effective site-specific administration remains undefined. This study
      was performed to determine the required theoretical dose of the somatostatin
      analogue, octreotide, to be delivered site specifically, for prevention of
      restenosis after coronary angioplasty in humans using a previously described
      methodology to determine regional pharmacokinetics of site-specific intracoronary
      administrated compounds. In 7 patients, 111In-octreotide, a gamma-labeled
      somatostatin analogue, was infused post angioplasty at the site of dilatation via
      a coil-balloon and quantified using a radio-isotopic technique. Efficiency of
      delivery ranged from 0.1% to 2.7% of the total infused dose of 0.18 microg,
      corresponding to a mean peak delivered amount of 1.8 +/- 1.9 ng. Total locally
      bioavailable 111In-octreotide reached 2.28 +/- 2.15 ng h. Based on current in
      vitro bioavailability and peak concentration data to inhibit proliferation and
      thymidine incorporation in human coronary smooth muscle cells, a 4000x higher
      averaged dose (approximately 700 microg) should be infused site specifically to
      obtain a biologic efficacy in 50% of the treated patients (ED50). Quantification
      of regional pharmacokinetics enables the determination of a theoretical site
      specific dose for achieving appropriate bioavailability above the therapeutic
      threshold concentration for smooth muscle cell inhibition. This approach is
      proposed for the determination of the appropriate site-specific coronary infusion
      dose for the inhibition of restenosis after balloon angioplasty.

PMID- 14668580
TI  - Omapatrilat decreased macrophage oxidative status and atherosclerosis progression
      in atherosclerotic apolipoprotein E-deficient mice.
AB  - Oxidative stress is an important risk factor in the pathogenesis of
      atherosclerosis. Angiotensin-converting enzyme (ACE) inhibitors attenuate
      atherosclerosis and oxidative stress in animal models. Omapatrilat, a
      VasoPeptidase-inhibitor, selectively inhibits both Neutral-Endo-Peptidase (NEP)
      and ACE. OBJECTIVE: In this study, we analyzed the effect of Omapatrilat
      administration (1, 4, or 20mg/kg/d, for 12 weeks) to atherosclerotic
      apolipoprotein E-deficient (E0) mice on their blood pressure (BP), serum and
      macrophage oxidative status, and atherosclerotic lesion area. RESULTS: Following
      administration of Omapatrilat (4 mg/kg/d and 20 mg/kg/d), the mice systolic and
      diastolic BP significantly decreased by up to 33% and 25% respectively, compared
      with placebo-treated mice. However, administration of Omapatrilat at 1mg/kg/d did
      not affect the mice BP. The Omapatrilat-treated mice serum susceptibility to
      lipid peroxidation was reduced by up to 21%, and their serum paraoxonase activity
      was increased by up to 24%, compared with placebo-treated mice. Peritoneal
      macrophages from Omapatrilat-treated (20 mg/kg/d) mice exhibited a reduced
      oxidative stress, evidenced by a reduction in macrophage lipid peroxide content
      (by 45%), cholesteryl-linoleate hydroperoxide content (by 48%), and oxidized
      glutathione levels (by 40%). Finally, the area of the mice atherosclerotic lesion
      was dose-dependently reduced, by 50%, 67%, and 82%, following Omapatrilat
      administration at 1mg/kg/d, 4 mg/kg/d, and 20 mg/kg/d respectively, compared with
      placebo-treated mice. CONCLUSION: Omapatrilat has a substantial anti
      atherosclerotic effect, which can be related not only to BP reduction but also to
      its ability to reduce oxidative stress in atherosclerotic E0 mice.

PMID- 14668581
TI  - Antioxidant activity of nebivolol in the rat aorta.
AB  - The beta-blocker nebivolol is a racemic mixture of D- and L- enantiomers that
      displays negative inotropic as well as direct vasorelaxant activity. In addition,
      it has been proposed that nebivolol exerts endothelium-protective effects caused
      by its antioxidant properties. In the present study we investigated the effect of
      D-, L-, and d/l-nebivolol on reactive oxygen species (ROS)-induced endothelial
      damage and compared it with carvedilol and metoprolol. Isolated rat aortic rings
      were exposed to ROS by electrolysis of the organ bath medium. Before and after
      electrolysis, endothelial function was measured by preconstricting the vessels
      with phenylephrine followed by the addition of methacholine. Carvedilol and
      nebivolol protected against ROS-induced endothelial damage, whereas metoprolol
      did not. The protective effect of nebivolol proved not to be stereoselective.
      Furthermore, we attempted to determine whether nebivolol acts a scavenger itself
      or whether another mechanism is involved. By means of HPLC measurements it was
      shown that nebivolol concentrations were decreased after exposure to electrolysis
      induced ROS, thus indicating that nebivolol is degraded by its reaction with ROS.
      Functional experiments, in the rat aorta, demonstrated that exposure of nebivolol
      to ROS also affects its vasodilator activity. In conclusion, the present study
      demonstrates that nebivolol alleviates ROS-induced impairment of endothelium
      dependent vasorelaxation. This protective effect is very likely the result of a
      direct ROS-scavenging action by the nebivolol molecule itself.

PMID- 14668582
TI  - Involvement of reactive oxygen species in angiotensin II-induced
      vasoconstriction.
AB  - In recent years it has been shown that angiotensin II (Ang II) stimulates
      formation of reactive oxygen species (ROS), presumably by activation of NAD(P)H
      oxidase. This ROS formation has been primarily associated with cellular growth
      regulation by Ang II. The objective of the present study was to investigate
      whether these ROS contribute to Ang II-induced vasoconstriction. Experiments were
      performed in isolated rat thoracic aorta. Concentration response curves were
      constructed for Ang II in the absence and presence of the NAD(P)H oxidase
      inhibitor DPI, and ROS scavengers catalase and EUK-8. Inhibition of NAD(P)H
      oxidase as well as scavenging of ROS, decreased the contractile response to Ang
      II. Administration of NADPH, a substrate for NAD(P)H oxidase, produced
      vasoconstriction that proved to be sensitive for DPI, catalase, and EUK-8.
      Exposure of the vessels to exogenous ROS, induced by electrolysis of the organ
      bath medium, also resulted in a contractile response that was decreased by ROS
      scavenging. The results suggest that ROS play a role in Ang II-induced
      vasoconstriction via the activation of NAD(P)H oxidase.

PMID- 14668583
TI  - Measuring fecal incontinence.
AB  - The measurement of fecal incontinence is challenging. Because fecal incontinence
      is a symptom, the subjective perception of the patient must be the foundation of
      any evaluation of incontinence or the impact of incontinence. The lack of a
      criterion standard makes testing measures for reliability and validity more
      difficult. Despite this, many measures are available and can be divided into
      three broad categories: descriptive measures that do not provide summary scores;
      severity measures that assess the frequency and type of incontinence; and impact
      measures that assess the effect of incontinence on quality of life. The strengths
      and weaknesses of currently available measures are presented in this review.

PMID- 14668584
TI  - Safety and effectiveness of temperature-controlled radio-frequency energy
      delivery to the anal canal (Secca procedure) for the treatment of fecal
      incontinence.
AB  - PURPOSE: This multicenter study evaluated the safety and efficacy of radio
      frequency energy delivery to the anal canal for the treatment of fecal
      incontinence. METHODS: Fifty patients at five centers were enrolled. All reported
      fecal incontinence at least once per week for three months, and medical and/or
      surgical management failed to help their symptoms. At baseline and at six months,
      patients completed questionnaires (Cleveland Clinic Florida Fecal Incontinence
      score (0-20), fecal incontinence-related quality of life, Short Form-36, and
      visual analog scale) and underwent anorectal manometry, endoanal ultrasound, and
      pudendal nerve terminal motor latency testing. On an outpatient basis using local
      anesthesia, radio-frequency energy was delivered via an anoscopic device with
      multiple needle electrodes (Secca system) to create thermal lesions deep to the
      mucosa of the anal canal. RESULTS: Forty-three females and seven males (aged 61.1
      +/- 13.4 (mean +/- standard deviation); range, 30-80 years) were treated. Mean
      duration of fecal incontinence was 14.9 years. Treatment time was 37 +/- 9
      minutes. At six months, the mean Cleveland Clinic Florida Fecal Incontinence
      score improved from 14.5 to 11.1 (P < 0.0001). All parameters in the Fecal
      Incontinence Quality of Life scales were improved (lifestyle (from 2.5-3.1; P <
      0.0001); coping (from 1.9-2.4; P < 0.0001), depression (from 2.8-3.3; P =
      0.0004); embarrassment (from 1.9-2.5; P < 0.0001)). Responders, as assessed by a
      systematic referenced analog scale, reported a median 70 percent resolution of
      symptoms. The mean Short Form-36 social function improved from 64.3 to 76 (P =
      0.003). There were no changes in endoanal ultrasound or pudendal nerve terminal
      motor latency assessment, or in anal manometry. Complications included mucosal
      ulceration (one superficial, one with underlying muscle injury) and delayed
      bleeding (n = 1). CONCLUSION: This multicenter trial demonstrates that radio
      frequency energy can be safely delivered to the lower rectum and anal canal. The
      Secca procedure significantly improved the Cleveland Clinic Florida Fecal
      Incontinence score and the overall quality of life for most patients having
      undergone the procedure.

PMID- 14668586
TI  - Contemporary outcomes of total pelvic exenteration in the treatment of colorectal
      cancer.
AB  - PURPOSE: Total pelvic exenteration is performed infrequently in selected patients
      with locally advanced or recurrent colorectal cancer. We reviewed our
      contemporary experience with pelvic exenteration for colorectal cancer to
      identify selection criteria and prognostic factors for long-term survival.
      METHODS: Between 1991 and 2000, 55 patients (males, 29; median age, 62 years)
      undergoing total pelvic exenteration for colorectal cancer were identified from a
      prospective database. Clinicopathologic variables were evaluated as prognostic
      indicators of long-term survival by log-rank test and multivariate Cox
      regression. RESULTS: Indications for surgery were recurrent colorectal cancer in
      71 percent and primary colorectal cancer in 29 percent. Of 39 patients with
      recurrent colorectal cancer, 85 percent had previous radiotherapy, and 64 percent
      had previous abdominoperineal resection. At the time of pelvic exenteration, 49
      percent of patients received intraoperative radiation, and 20 percent required
      sacrectomy. Complete resection with negative margins was achieved in 73 percent.
      Perioperative mortality after pelvic exenteration was 5.5 percent, and
      complications included perineal wound infection (40 percent), pelvic abscess (20
      percent), abdominal wound infection (18 percent), and cardiopulmonary events (18
      percent). Median disease-specific survival for all patients was 48.9 (range, 3.2
      105.6) months. Univariate analysis identified five factors associated with
      decreased survival: male gender, recurrent colorectal cancer, previous
      abdominoperineal resection, positive surgical margin, and administration of
      intraoperative radiation. On multivariate analysis, only previous
      abdominoperineal resection was an independent predictor of unfavorable outcome (P
      < 0.04). CONCLUSIONS: Total pelvic exenteration can be performed safely in highly
      selected patients with colorectal cancer and can result in significantly
      prolonged survival. Less satisfactory outcomes are observed in patients whose
      indication for pelvic exenteration is recurrent colorectal cancer after
      abdominoperineal resection.

PMID- 14668587
TI  - Predictive factors for lymph node metastasis in T1 stage colorectal carcinomas.
AB  - PURPOSE: Selective endoscopic resection may cure early colorectal cancer (T1),
      but the management is controversial. There is concern about the small risk of
      lymph node metastasis, which will not be treated by endoscopic resection alone.
      The authors sought predictive markers of lymph node metastasis to assist patient
      management. METHODS: The authors retrospectively analyzed consecutive cases of T1
      stage colorectal cancer resected using endoscopic resection or bowel surgery over
      the period 1979 to 2000. The risk of lymph node metastasis was analyzed using
      logistic regression model for the markers selected by univariate analysis: the
      type of initial treatment, depth of submucosal invasion, lymphatic channel
      invasion, differentiation of histology, and invasive front histology. RESULTS:
      Two hundred seventy-eight patients were available for study. Twenty-one had lymph
      node metastasis. Depth of submucosal invasion (> or = 2,000 microm) and lymphatic
      channel invasion significantly predicted risk of lymph node metastasis in
      multivariate analysis. When these two factors were adopted for the prediction of
      lymph node metastasis, sensitivity, specificity, positive predictive value, and
      negative predictive value were 100, 55.6, 15.6, and 100 percent, respectively.
      CONCLUSIONS: Depth of submucosal invasion and lymphatic channel invasion were
      accurate predictive factors for lymph node metastasis. These two factors could be
      used in selecting appropriate cases for surgery after endoscopic resection.

PMID- 14668589
TI  - Single-surgeon surgery in laparoscopic colonic resection.
AB  - PURPOSE: Short-term benefits have been demonstrated for laparoscopic-assisted
      colectomy. However, minimally invasive surgery is still in an evolutionary phase.
      In demonstrating that robotic devices also are useful in laparoscopic colonic
      surgery, it is fundamental to prove that a single surgeon can perform almost the
      entire operation on his own. METHODS: A single surgeon performed forty-one,
      laparoscopic-assisted, colorectal resections with the assistance of a robotic
      device (Automated Endoscopic System for Optimal Positioning, Computer Motion)
      maneuvering the laparoscope. A surgical assistant was included only for the open
      part of the operation. Main outcome measures were conversion rate, total
      operating time, and percentage of assistance by a second surgeon. RESULTS: There
      were no intraoperative complications, one case of conversion to open surgery, and
      three postoperative complications. The total operating time ranged from 126 to
      252 minutes. A single surgeon with the assistance of a robotic device was able to
      perform approximately 70 percent of an ileocecal resection, 70 percent of a right
      hemicolectomy, 80 percent of a sigmoid resection, and 85 percent of a anterior
      rectal resection without further help of a surgeon. CONCLUSIONS: A single surgeon
      with the assistance of a computerized robotic system can complete at least two
      thirds of a laparoscopic-assisted, colorectal resection on his own. The use of a
      robotic device in laparoscopic-assisted, colonic surgery is safe, efficient, and
      feasible, and will prove even more so in future. This also will result in a
      patient-driven demand for high-standard, minimally invasive surgery.

PMID- 14668588
TI  - Comparison of robotically performed and traditional laparoscopic colorectal
      surgery.
AB  - INTRODUCTION: Robotic laparoscopic surgery is postulated to result in better
      surgical results by allowing improved instrument manipulation and three
      dimensional vision. The authors' experience performing robot-assisted
      laparoscopic colorectal surgery is reported. METHOD: Standard laparoscopic
      procedures with robot-assisted laparoscopic colon mobilization and vascular
      ligation were performed. Data relating to the operative procedure, hospital stay,
      and direct costs were collected. Results were compared with age, gender, and
      procedure case-matched controls taken from a prospective laparoscopic colorectal
      surgery database. RESULTS: Six robot-assisted laparoscopic surgeries (2 right
      hemicolectomies, 3 sigmoid colectomies, and 1 Wells rectopexy) were performed
      between December 2001 and June 2002. There was no associated morbidity. Operative
      time was increased from a median time of 108 minutes for standard laparoscopic
      colorectal surgery to 165 minutes for robot-assisted laparoscopic surgeries (P =
      0.0313; Wilcoxon matched-pairs signed-rank test for nonparametric data). This was
      primarily a result of the time required for robot set-up. Blood loss, length of
      stay, and hospital cost were not significantly different between groups.
      Additional direct equipment costs for RAC cases included robotic laparoscopic
      instruments and sterile drapes (approximately US $350 per case), without
      including acquisition and maintenance costs for the robot. CONCLUSION: Robot
      assisted laparoscopic colectomy is a feasible and safe procedure. Although three
      dimensional vision and dexterity are facilitated, operative time is increased and
      the overall additional expense of robotics is of concern. Robot-assisted
      laparoscopic colectomy requires further evaluation to establish clinical and
      financial benefits before introduction to routine practice. Such techniques may,
      in the future, facilitate complex laparoscopic techniques.

PMID- 14668590
TI  - How aggressive should we be in patients with stage IV colorectal cancer?
AB  - PURPOSE: The prognosis for metastatic colorectal cancer is grave. Whether to
      perform surgical resection or palliative treatment remains controversial for this
      advanced disease. In this retrospective study, we collected data from patients
      with Stage IV colorectal cancer to identify prognostic factors for predicting
      selection criteria for surgical treatment in patients with metastatic disease.
      METHODS: A retrospective chart review was performed for patients treated from
      1992 to 1999 from the Koo Foundation Sun Yat-Sen Cancer Center Tumor Registry.
      Seventy-four patients were identified as having Stage IV disease at the time of
      diagnosis. Data concerning the patients' demographics, laboratory results,
      operative procedure, mortality, morbidity, and survival were collected.
      Independent variables and survival time were analyzed by the independent t-test
      method. The difference was considered statistically significant at P < 0.05.
      RESULTS: Overall survival time for the patients with Stage IV colorectal cancer
      was 16.1 months. Survival in the curative resection group was significantly
      longer than that in the noncurative group (31.9 vs. 12.7; P < 0.016). The
      operative mortality and morbidity rates were 5.6 percent (4 of 71) and 21.1
      percent (15 of 71), respectively. The two most common complications were leakage
      at the site of anastomosis and urinary tract infection. Based on these results,
      we conclude that patients older than 65 years, with metastases at multiple sites,
      intestinal obstruction, preoperative carcinoembryonic antigen level > or =500
      ng/ml, lactate dehydrogenase > or =350 units/liter, hemoglobin <10 mg/dl, or
      hepatic parenchymal replacement by tumor >25 percent have poor prognosis for
      surgical intervention. CONCLUSION: Whether to perform primary tumor resection in
      patients with asymptomatic Stage IV colorectal cancer remains controversial;
      however, the more aggressively we perform radical resection and metastasectomy to
      selected patients, the more survival benefits the patients obtain.

PMID- 14668591
TI  - Carcinoembryonic antigen mRNA in the mesenteric vein is not a predictor of
      hepatic metastasis in patients with resectable colorectal cancer: a long-term
      study.
AB  - PURPOSE: The clinical value of carcinoembryonic antigen messenger ribonucleic
      acid in the draining venous blood has been controversial because of short
      observation period. The authors prospectively investigated the clinical
      significance of detection of carcinoembryonic antigen messenger ribonucleic acid
      in the draining venous blood to predict hepatic metastases in patients with
      resectable colorectal cancer. METHODS: Drainage venous blood from 80 patients who
      underwent curative resections for colorectal cancer were obtained immediately
      before surgery to determine the presence of cancer cells by means of reverse
      transcription polymerase chain reaction. RESULTS: After an average follow-up
      period of 52.1 months, 7 of the 35 patients (20 percent) with positive
      carcinoembryonic antigen messenger ribonucleic acid had hepatic metastases,
      whereas 2 of the 45 patients (4.5 percent) with negative carcinoembryonic antigen
      messenger ribonucleic acid had hepatic metastases. The cumulative probability of
      hepatic metastatic recurrence rate differed significantly between two patient
      groups with positive or negative carcinoembryonic antigen messenger ribonucleic
      acid expression in the drainage vein (log-rank, 4.900; P = 0.0269). However, 28
      of the 35 patients (80 percent) with positive carcinoembryonic antigen messenger
      ribonucleic acid did not have hepatic metastases. Additionally, Cox proportional
      hazards models identified the presence of lymph node metastases as the only
      independent predictor of hepatic metastatic recurrence. CONCLUSIONS: This study
      failed to demonstrate the high predictive value of carcinoembryonic antigen
      messenger ribonucleic acid detection in the draining venous blood for the
      development of hepatic metastases. However, the authors demonstrated that the
      presence of cancer cells in the draining venous blood was the essential and
      initial step to the development of hepatic metastasis.

PMID- 14668592
TI  - Clinical application of radioimmunoguided surgery in colorectal cancer using 125I
      labeled carcinoembryonic antigen-specific monoclonal antibody submucosally.
AB  - PURPOSE: The aim of this study was to evaluate the applicability of 125I-labeled
      carcinoembryonic antigen-specific monoclonal antibody CL58 in clinical
      radioimmunoguided surgery for colorectal cancer. METHODS: First, we tested the
      purity and affinity constant of CL58 and measured the binding affinity of CL58 to
      colorectal cancer cells and normal cells. Second, we injected 125I-labeled CL58
      into nude mice with colon cancers. Then, samples from the tumor, blood, and
      normal tissues of injected mice were weighed and counted in a gamma-ray counter
      for assessment of biodistribution. Finally, we administered 125I-labeled CL58
      submucosally in 29 patients with colorectal cancer via endoscope.
      Radioimmunoguided surgery was performed 3 to 14 days later with a portable gamma
      detecting probe to obtain the counts in the target sites. Tumor-to-normal tissue
      ratio of 3 was taken as the lowest positive threshold value for primary lesions,
      wall infiltration, and lymph node metastasis. In addition, all the samples were
      examined by routine histopathology. Lymph nodes negative by routine
      histopathology were subjected to immunohistochemical staining with
      anticytokeratin to detect the lymphatic micrometastasis. RESULTS: The affinity
      constant of CL58 was 7.5 x 109 M-. Moreover, CL58 reacted strongly to the
      colorectal cancer cell lines, but not to the normal control cells. Furthermore,
      the tumor tissues showed significant intake of 125I-labeled CL58, as compared
      with that of normal tissues. The sensitivity of radioimmunoguided surgery in
      detecting primary lesions was 93.1 percent, and the specificity of
      radioimmunoguided surgery to correctly identify negative incisional margins for
      tumor infiltration was 95.5 percent. For the detection of lymphatic metastasis,
      the sensitivity of radioimmunoguided surgery was 92.0 percent and the specificity
      was 87.8 percent. The sensitivity of radioimmunoguided surgery in detecting lymph
      node metastasis was significantly higher when compared with traditional clinical
      methods (P = 0.0087). The specificity of radioimmunoguided surgery to identify
      negative incisional margins was also significantly higher when compared with
      traditional clinical methods (P = 0.0117). The sensitivity and specificity of
      radioimmunoguided surgery in detecting lymph nodes metastasis showed statistical
      significance, as compared with traditional clinical methods. Immunohistochemistry
      verified the existence of lymphatic micrometastasis in radioimmunoguided surgery
      positive but histology-negative lymph nodes. CONCLUSIONS: This study indicates
      that radioimmunoguided surgery for colorectal cancer using 125I-labeled
      anticarcinoembryonic antigen monoclonal antibody submucosally enables surgeons to
      define lymphatic metastasis, thus successfully guiding surgeons in performing
      personalized radical operation.

PMID- 14668593
TI  - Rectal endometriosis: high sensitivity and specificity of endorectal ultrasound
      with an impact for the operative management.
AB  - PURPOSE: In patients with histopathologically proven or suspected endometriosis
      with possible involvement of the rectum, endorectal ultrasound was performed to
      determine the sensitivity and specificity of this method with regard to rectal
      wall involvement and the impact on the following operation. METHODS: In an
      historical cohort analysis, 85 females with histopathologically proven or
      suspected endometriosis with possible involvement of the rectum were treated
      between 1992 and 2001. Endorectal ultrasound was performed with a 7.5 MHz real
      time unit, and results of endorectal ultrasound were compared with intraoperative
      findings and histopathologic diagnosis of 65 patients undergoing operation. A
      questionnaire was used to evaluate postoperative signs and symptoms. RESULTS: Of
      65 patients undergoing surgery, 37 underwent laparotomy with 25 resections of the
      bowel and 28 laparoscopy. In 31 of 32 patients with suspected rectal wall
      infiltration, preoperative endorectal ultrasound diagnosis was confirmed. In
      patients in whom endorectal ultrasound showed no rectal wall involvement,
      histopathology revealed infiltration in one patient, leading to sensitivity of 97
      percent and specificity of 97 percent with regard to rectal wall involvement. In
      terms of the deepness of rectal wall infiltration, endorectal ultrasound had a
      sensitivity of 76 percent with regard to infiltration of the muscularis propria
      and 66 percent for infiltration of the submucosa. Operations led to a significant
      (P < 0.05) reduction of preoperative symptoms by approximately 60 percent.
      CONCLUSIONS: Endorectal ultrasound is a useful, noninvasive technique for
      preoperative evaluation of possible rectal wall involvement in endometriosis.
      Based on the high sensitivity and specificity, recommendation for laparotomy and
      bowel resection in cases with suspected rectal involvement can be facilitated.

PMID- 14668594
TI  - Impact of two different types of anal retractor on fecal continence after fistula
      repair: a prospective, randomized, clinical trial.
AB  - PURPOSE: This study was designed to compare two different types of anal
      retractors (Parks vs. Scott) with regard to their impact on fecal continence
      after fistula repair. METHODS: Between November 2000 and November 2001, 30
      patients were randomized into two groups. In Group A (n = 15), a Parks retractor
      was used during fistula repair, whereas in Group B (n = 15), the repair was
      performed with a Scott retractor. Before and three months after surgery, maximum
      anal resting pressure and maximum anal squeeze pressure were recorded. In
      addition, continence status was evaluated using both the Rockwood Fecal
      Incontinence Severity Index and the scoring system according to Parks. RESULTS:
      In Group A, the median anal resting pressure dropped from 76 mmHg to 42 mmHg. In
      Group B, no significant difference was observed between the preoperative and
      postoperative anal resting pressure. The difference in the changes from baseline
      between the two groups was statistically significant (P = 0.035). No significant
      changes in anal squeeze pressure were observed. In Group A, the median Rockwood
      fecal incontinence score increased from 0 to 12. In Group B, the median Rockwood
      fecal incontinence score did not change after the operation. The difference
      between the two groups was statistically significant (P = 0.038). CONCLUSIONS:
      The use of a Parks retractor during perianal fistula repair has a deteriorating
      effect on fecal continence, probably because of damage to the internal anal
      sphincter. Because this side effect was not observed after the use of a Scott
      retractor, we advocate the use of this retractor during all fistula repairs.

PMID- 14668595
TI  - Feasibility of early closure of loop ileostomies: a pilot study.
AB  - PURPOSE: A loop ileostomy is constructed to protect a distal anastomosis, and
      closure is usually performed not earlier than after two to three months. Earlier
      closure might reduce stoma-related morbidity, improve quality of life, and still
      effectively protect the distal anastomosis. This pilot study was designed to
      investigate the feasibility of early closure of loop ileostomies, i.e., during
      the same hospital admission as the initial operation. METHODS: Twenty-seven
      consecutive patients with a protective loop ileostomy were included. If patient's
      recovery was uneventful, water-soluble contrast enema examination was performed,
      preferably after seven to eight days. If no radiologic signs of leakage were
      detected, the ileostomy was closed during the same hospital admission. RESULTS:
      Twenty-seven patients (8 females; mean age, 60 years) were analyzed. Eighteen
      patients had early ileostomy closure on average 11 (range, 7-21) days after the
      initial procedure. In nine patients the procedure was postponed because of
      leakage of the anastomosis (n = 3), delayed recovery (n = 1), small bowel
      obstruction (n = 1), gastroparesis (n = 1), logistic reasons (n = 2), or
      irradical cancer resection followed by radiotherapy (n = 1). There was no
      mortality and four mild complications occurred after early closure: superficial
      wound infection (n = 2), intravenous-catheter sepsis (n = 1), small bowel
      obstruction (n = 1). CONCLUSION: Closure of a loop ileostomy early after the
      initial operation was feasible in 18 of 27 patients and was associated with low
      morbidity and no mortality.

PMID- 14668596
TI  - Increased anal resting pressure and rectal sensitivity in Crohn's disease.
AB  - PURPOSE: Anal pathology occurs in 20 to 80 percent of patients with Crohn's
      disease in which abscesses, fistulas, and fissures account for considerable
      morbidity. The etiology is not clearly defined, but altered anorectal pressures
      may play a role. This study was designed to investigate anorectal physiologic
      conditions in patients with Crohn's disease compared with healthy controls.
      METHODS: Twenty patients with Crohn's disease located in the ileum (n = 9) or the
      colon (n = 11) without macroscopic proctitis or perianal disease were included.
      All were subjected to rectal examination, anorectal manometry, manovolumetry, and
      rectoscopy. Comparison was made with a reference group of 173 healthy controls of
      whom 128 underwent anorectal manometry, 29 manovolumetry, and 16 both
      examinations. RESULTS: Maximum resting pressure and resting pressure area were
      higher in patients than in controls (P = 0.017 and P = 0.011, respectively),
      whereas maximum squeeze pressure and squeeze pressure area were similar. Rectal
      sensitivity was increased in patients expressed as lower values both for volume
      and pressure for urge (P = 0.013 and P = 0.014, respectively) as well as maximum
      tolerable pressure (P = 0.025). CONCLUSIONS: This study demonstrates how patients
      with Crohn's disease without macroscopic proctitis have increased anal pressures
      in conjunction with increased rectal sensitivity. This may contribute to later
      development of anal pathology, because increased intra-anal pressures may
      compromise anal circulation, causing fissures, and also discharging of fecal
      matter into the perirectal tracts, which may have a role in infection and fistula
      development.

PMID- 14668597
TI  - Effects of recombinant human growth hormone and nandrolone phenylpropionate on
      the healing of ischemic colon anastomosis in rats.
AB  - PURPOSE: Recombinant human growth hormone and nandrolone phenylpropionate are two
      different anabolic agents. This study was designed to investigate the effects of
      these anabolic agents on the healing of ischemic colon anastomosis in rats.
      METHODS: Seventy adult male Wistar rats were divided into five groups (n = 14).
      Group I was the sham laparotomy group. In the other groups, surgical procedures
      consisting of transsection and anastomosis were made at a distance 3 cm from the
      peritoneal reflection. Group II was the nonischemic control group. Ischemic colon
      model was produced in the remaining groups. Group III was the untreated control
      group. Groups IV and V received recombinant human growth hormone and nandrolone
      phenylpropionate, respectively. Bursting pressure and hydroxyproline levels were
      measured on the third and seventh postoperative days to evaluate anastomotic
      healing. RESULTS: Recombinant human growth hormone increased both collagen
      deposition and bursting pressure significantly at postoperative Days 3 and 7
      compared with the sham and untreated control groups (P < 0.005). When compared
      with the untreated control, nandrolone phenylpropionate significantly increased
      collagen deposition at postoperative Days 3 and 7 (P < 0.005) and bursting
      pressure only at postoperative Day 3 (P < 0.005). CONCLUSIONS: Recombinant human
      growth hormone has more favorable therapeutic effects on the healing of ischemic
      colonic anastomoses than nandrolone phenylpropionate. Recombinant human growth
      hormone also improves healing of nonischemic colonic anastomosis.

PMID- 14668598
TI  - Familial adenomatous polyposis and duodenal lymphoma: report of a case.
AB  - The occurrence of duodenal polyposis is well recognized in familial adenomatous
      polyposis. Lymphoid hyperplasia in association with familial adenomatous
      polyposis usually occurs in the terminal ileum, but it can occur in the duodenum
      and may be endoscopically difficult to distinguish from an adenoma. A case report
      is presented in which a 54-year-old male with familial adenomatous polyposis, who
      20 years earlier had a subtotal colectomy and ileorectal anastomosis, presented
      with a large rectal villous tumor and was found to have a duodenal extranodal
      marginal zone lymphoma of mucosa-associated lymphoid tissue. The role of lymphoid
      hyperplasia in the development of mucosa-associated lymphoid tissue lymphoma is
      discussed, as well as the issue of mucosa-associated lymphoid tissue lymphoma in
      familial adenomatous polyposis. In cases in which biopsies of polypoid lesions in
      patients with familial adenomatous polyposis show dense lymphoid aggregates, flow
      cytometry may assist in the diagnosis.

PMID- 14668599
TI  - Rectal adenocarcinoma with germ-cell differentiation: report of a case.
AB  - A 26-year-old male presented with a colorectal adenocarcinoma with germ-cell
      differentiation and an isolated elevation of serum alpha-fetoprotein. He was
      treated with platinum/etoposide/bleomycin chemotherapy with a decrease in serum
      alpha-fetoprotein and in the size of the primary tumor. An ongoing tumor-marker
      response occurred when the patient was switched to concurrent 5-fluorouracil
      chemotherapy and radiation therapy. The patient underwent a palliative diversion
      of his rectal cancer 10 months after diagnosis, developed liver metastasis at 12
      months, and died 20 months after diagnosis.

PMID- 14668600
TI  - Subtotal colectomy and cecosigmoid anastomosis for colonic systemic sclerosis:
      report of a case and review of the literature.
AB  - PURPOSE: We report a case of subtotal colonic involvement of systemic sclerosis,
      successfully managed by subtotal colectomy and cecosigmoid anastomosis, and
      review the literature on surgical management. METHODS: A patient had profound
      slow transit constipation and severe colonic involvement on nuclear transit
      study. Surgery was conservative, with preservation of distal sigmoid colon and
      the ileocecal valve. A literature search regarding management of colonic systemic
      sclerosis was conducted. RESULTS: The surgery was uncomplicated and near normal
      bowel function was restored. The literature indicates that colonic involvement is
      common in systemic sclerosis and that surgery is sometimes required for severe
      disease or the development of complications. CONCLUSIONS: If surgery is required
      for colonic involvement in systemic sclerosis, it should be directed at the
      segmental distribution of the disease, preserving the colon if possible and
      considering the possibility of concurrent small-bowel involvement. Nuclear
      colonic transit study is helpful in guiding the extent of surgery.

PMID- 14668601
TI  - Pursestring placement before transsection of the rectum for facilitating the
      stapled low colorectal anastomosis.
AB  - We propose a simple, easy technique to perform a stapled colorectal anastomosis
      close to the anal sphincter that may help to lower leak rates. This is the same
      technique used by us for successful performance of intrathoracic and abdominal
      esophagoenteric mechanical anastomoses. The technique consists of hand sewing a
      double pursestring suture before sectioning the rectum.

PMID- 14668602
TI  - Mesenteric vein thrombosis after proctocolectomy for inflammatory bowel disease.

PMID- 14668603
TI  - Idiopathic slow-transit constipation: an almost exclusively female disorder.

PMID- 14668604
TI  - Patients on bisphosphonates should not be at increased risk for hypocalcemic
      induced tetany when given Fleet Phospho-soda.

PMID- 14668605
TI  - Safety of botulinum toxin therapies.

PMID- 14668606
TI  - Quality of life after subtotal colectomy for constipation: selection of the right
      patient, operation, and tools to measure outcome.

PMID- 14668607
TI  - Prone position and positive end-expiratory pressure in acute respiratory distress
      syndrome.
AB  - OBJECTIVE: To determine whether positive end-expiratory pressure (PEEP) and prone
      position present a synergistic effect on oxygenation and if the effect of PEEP is
      related to computed tomography scan lung characteristic. DESIGN: Prospective
      randomized study. SETTING: French medical intensive care unit. PATIENTS: Twenty
      five patients with acute respiratory distress syndrome. INTERVENTIONS: After a
      computed tomography scan was obtained, measurements were performed in all
      patients at four different PEEP levels (0, 5, 10, and 15 cm H2O) applied in
      random order in both supine and prone positions. MEASUREMENTS AND MAIN RESULTS:
      Analysis of variance showed that PEEP (p <.001) and prone position (p <.001)
      improved oxygenation, whereas the type of infiltrates did not influence
      oxygenation. PEEP and prone position presented an additive effect on oxygenation.
      Patients presenting diffuse infiltrates exhibited an increase of Pao2/Fio2
      related to PEEP whatever the position, whereas patients presenting localized
      infiltrates did not have improved oxygenation status when PEEP was increased in
      both positions. Prone position (p <.001) and PEEP (p <.001) reduced the true
      pulmonary shunt. Analysis of variance showed that prone position (p <.001) and
      PEEP (p <.001) reduced the true pulmonary shunt. The decrease of the shunt
      related to PEEP was more pronounced in patients presenting diffuse infiltrates. A
      lower inflection point was identified in 22 patients (88%) in both supine and
      prone positions. There was no difference in mean lower inflection point value
      between the supine and the prone positions (8.8 +/- 2.7 cm H2O vs. 8.4 +/- 3.4 cm
      H2O, respectively). CONCLUSIONS: PEEP and prone positioning present additive
      effects. The prone position, not PEEP, improves oxygenation in patients with
      acute respiratory distress syndrome with localized infiltrates.

PMID- 14668608
TI  - Decrease in PaCO2 with prone position is predictive of improved outcome in acute
      respiratory distress syndrome.
AB  - OBJECTIVE: To determine whether gas exchange improvement in response to the prone
      position is associated with an improved outcome in acute lung injury (ALI)/acute
      respiratory distress syndrome (ARDS). DESIGN: Retrospective analysis of patients
      in the pronation arm of a controlled randomized trial on prone positioning and
      patients enrolled in a previous pilot study of the prone position. SETTING:
      Twenty-eight Italian and two Swiss intensive care units. PATIENTS: We studied 225
      patients meeting the criteria for ALI or ARDS. INTERVENTIONS: Patients were in
      prone position for 10 days for 6 hrs/day if they met ALI/ARDS criteria when
      assessed each morning. Respiratory variables were recorded before and after 6 hrs
      of pronation with unchanged ventilatory settings. MEASUREMENTS AND MAIN RESULTS:
      We measured arterial blood gas alterations to the first pronation and the 28-day
      mortality rate. The independent risk factors for death in the general population
      were the Pao2/Fio2 ratio (odds ratio, 0.992; confidence interval, 0.986-0.998),
      the minute ventilation/Paco2 ratio (odds ratio, 1.003; confidence interval, 1.000
      1.006), and the concentration of plasma creatinine (odds ratio, 1.385; confidence
      interval, 1.116-1.720). Pao2 responders (defined as the patients who increased
      their Pao2/Fio2 by > or =20 mm Hg, 150 patients, mean increase of 100.6 +/- 61.6
      mm Hg [13.4 +/- 8.2 kPa]) had an outcome similar to the nonresponders (59
      patients, mean decrease -6.3 +/- 23.7 mm Hg [-0.8 +/- 3.2 kPa]; mortality rate
      44% and 46%, respectively; relative risk, 1.04; confidence interval, 0.74-1.45, p
      =.65). The Paco2 responders (defined as patients whose Paco2 decreased by > or =1
      mm Hg, 94 patients, mean decrease -6.0 +/- 6 mm Hg [-0.8 +/- 0.8 kPa]) had an
      improved survival when compared with nonresponders (115 patients, mean increase 6
      +/- 6 mm Hg [0.8 +/- 0.8 kPa]; mortality rate 35.1% and 52.2%, respectively;
      relative risk, 1.48; confidence interval, 1.07-2.05, p =.01). CONCLUSION:
      ALI/ARDS patients who respond to prone positioning with reduction of their Paco2
      show an increased survival at 28 days. Improved efficiency of alveolar
      ventilation (decreased physiologic deadspace ratio) is an important marker of
      patients who will survive acute respiratory failure.

PMID- 14668609
TI  - Relationship of pulmonary artery catheter use to mortality and resource
      utilization in patients with severe sepsis.
AB  - OBJECTIVE: To examine the relationship of pulmonary artery catheter (PAC) use to
      patient outcomes, including mortality rate and resource utilization, in patients
      with severe sepsis in eight academic medical centers. DESIGN: Case-control,
      nested within a prospective cohort study. SETTING: Eight academic tertiary care
      centers. PATIENTS: Stratified random sample of 1,010 adult admissions with severe
      sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome
      measures were in-hospital mortality, total hospital charge, and length of stay
      (LOS) for patients with and without PAC use. The case-matched subset of patients
      included 141 pairs managed with and without the use of a PAC. The mortality rate
      was slightly but not statistically significantly lower among the PAC use group
      compared with those not using a PAC (41.1% vs. 46.8%, p =.34). Even this trend
      disappeared after we adjusted for the Charlson comorbidity score and sepsis
      specific Acute Physiology and Chronic Health Evaluation (APACHE) III (adjusted
      odds ratio, 1.02; 95% confidence interval, 0.61-1.72). In linear regression
      models adjusted for the Charlson comorbidity score, sepsis-specific APACHE III,
      surgical status, receipt of a steroid before sepsis onset, presence of a Hickman
      catheter, and preonset LOS, no significant differences were found for total
      hospital charges (139,207 US dollars vs. 148,190, adjusted mean comparing PAC and
      non-PAC group, p =.57), postonset LOS (23.4 vs. 26.9 days, adjusted mean, p
      =.32), or total LOS in intensive care unit (18.2 vs. 18.8 days, adjusted mean, p
      =.82). CONCLUSIONS: Among patients with severe sepsis, PAC placement was not
      associated with a change in mortality rate or resource utilization, although
      small nonsignificant trends toward lower resource utilization were present in the
      PAC group.

PMID- 14668610
TI  - Impact of adequate empirical antibiotic therapy on the outcome of patients
      admitted to the intensive care unit with sepsis.
AB  - OBJECTIVES: Our primary goal was to evaluate the impact on in-hospital mortality
      rate of adequate empirical antibiotic therapy, after controlling for confounding
      variables, in a cohort of patients admitted to the intensive care unit (ICU) with
      sepsis. The impact of adequate empirical antibiotic therapy on early (<3 days),
      28-day, and 60-day mortality rates also was assessed. We determined the risk
      factors for inadequate empirical antibiotic therapy. DESIGN Prospective cohort
      study. SETTING: ICU of a tertiary hospital. PATIENTS: All the patients meeting
      criteria for sepsis at admission to the ICU. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Four hundred and six patients were included. Microbiological
      documentation of sepsis was obtained in 67% of the patients. At ICU admission,
      sepsis was present in 105 patients (25.9%), severe sepsis in 116 (28.6%), and
      septic shock in 185 (45.6%). By multivariate analysis, predictors of in-hospital
      mortality were Sepsis-related Organ Failure Assessment (SOFA) score at ICU
      admission (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.19-1.40), the
      increase in SOFA score over the first 3 days in the ICU (OR, 1.40; 95% CI, 1.19
      1.65), respiratory failure within the first 24 hrs in the ICU (OR, 3.12; 95% CI,
      1.54-6.33), and inadequate empirical antimicrobial therapy in patients with
      "nonsurgical sepsis" (OR, 8.14; 95% CI, 1.98-33.5), whereas adequate empirical
      antimicrobial therapy in "surgical sepsis" (OR, 0.37; 95% CI, 0.18-0.77) and
      urologic sepsis (OR, 0.14; 95% CI, 0.05-0.41) was a protective factor. Regarding
      early mortality (<3 days), factors associated with fatality were
      immunosuppression (OR, 4.57; 95% CI, 1.69-13.87), chronic cardiac failure (OR,
      9.83; 95% CI, 1.98-48.69) renal failure within the first 24 hrs in the unit (OR,
      8.63; 95% CI, 3.31-22.46), and respiratory failure within the first 24 hrs in the
      ICU (OR, 12.35; 95% CI, 4.50-33.85). Fungal infection (OR, 47.32; 95% CI, 5.56
      200.97) and previous antibiotic therapy within the last month (OR, 2.23; 95% CI,
      1.1-5.45) were independent variables related to administration of inadequate
      antibiotic therapy. CONCLUSIONS: In patients admitted to the ICU for sepsis, the
      adequacy of initial empirical antimicrobial treatment is crucial in terms of
      outcome, although early mortality rate was unaffected by the appropriateness of
      empirical antibiotic therapy.

PMID- 14668611
TI  - Implementation of an institutional program to improve clinical and financial
      outcomes of mechanically ventilated patients: one-year outcomes and lessons
      learned.
AB  - OBJECTIVE: To determine the effect of an institutional approach to the care of
      patients requiring mechanical ventilation for longer than three consecutive days
      in five adult intensive care units (ICU) on clinical and financial outcomes.
      DESIGN: A multidisciplinary team was selected from five adult ICUs to design the
      approach. Planning occurred from August 1999 to September 2000. The process was
      called outcomes management (OM) and included an evidence-based clinical pathway,
      protocols for weaning and sedation use, and the selection of four advanced
      practice nurses (called outcomes managers) to manage and monitor the program.
      SETTING: The project was completed in a 550-bed mid-Atlantic academic medical
      center. The ICUs included the following: coronary care, medical ICU, neuroscience
      ICU, surgical trauma ICU, and thoracic cardiovascular ICU. PATIENTS: The sample
      included 595 pre-OM patients and 510 post-OM patients mechanically ventilated for
      greater than three consecutive days. INTERVENTIONS: Full implementation of the OM
      approach occurred in March 2001. Retrospective baseline (18 months pre-OM) and
      prospective (12 months OM) clinical and financial data were compared.
      MEASUREMENTS AND MAIN RESULTS: Statistically significant differences in clinical
      outcomes were demonstrated in the managed patients compared with those managed
      before the institutional approach. Outcomes include ventilator duration (median
      days declined from ten to nine; p =.0001), ICU length of stay (median days
      declined from 15 to 12; p =.0008), hospital length of stay (median days declined
      from 22 to 20; p =.0001), and mortality rate (declined from 38% to 31%, p =.02).
      More than 3,000,000 US dollars cost savings were realized in the OM group.
      CONCLUSIONS: This institutional approach to the care of patients ventilated >3
      days improved all clinical and financial outcomes of interest. To date, few
      similar initiatives have demonstrated similar results. The approach and lessons
      learned in this process improvement project may be helpful to other institutions
      attempting to improve outcomes in this vulnerable population.

PMID- 14668612
TI  - Priority setting in a hospital critical care unit: qualitative case study.
AB  - OBJECTIVE: To describe priority setting for admissions in a hospital critical
      care unit and to evaluate it using the ethical framework of "accountability for
      reasonableness. DESIGN: Qualitative case study and evaluation using the ethical
      framework of accountability for reasonableness. SETTING: A medical/surgical
      intensive care unit in a large urban university-affiliated teaching hospital in
      Toronto, Canada. PARTICIPANTS: Critical care unit staff including medical
      directors, nurses, residents, referring physicians, and members of a hospital
      committee that formulated an admissions policy. INTERVENTIONS: Modified thematic
      analysis of documents, interviews with participants, and direct observation of
      critical care unit rounds. Evaluation using the four conditions of Daniels and
      Sabin's accountability for reasonableness: relevance, publicity,
      appeals/revisions, and enforcement. MEASUREMENTS AND MAIN RESULTS: We examined
      key features and participants' views about the priority setting process.
      Decisions to admit patients involve a complex cluster of reasons. Both medical
      and nonmedical reasons are used, although the nonmedical reasons are less well
      documented and understood. Medical directors, who are the chief decision makers,
      differ in their reasoning. Admitting decisions and reasons are usually explained
      to referring staff but seldom to patients and families, and nonmedical reasons
      are seldom surfaced. A hospital critical care admissions policy exists but is not
      used and is not known to all stakeholders. A formal appeals/revisions process
      exists, but appeals usually involve informal negotiations. The existence of
      priority programs in the hospital (e.g., transplantation) adds complexity and
      heightens disagreement by stakeholders. CONCLUSION: We have described and
      evaluated admissions decision making in a hospital's critical care unit. The key
      lesson of our study is not only the specific findings obtained here but also how
      combining a case study approach with the ethical framework of "accountability for
      reasonableness" can be used to identify good practices and opportunities for
      improving the fairness of priority setting in intensive care.

PMID- 14668613
TI  - Intrahepatic synthesis of tumor necrosis factor-alpha related to cardiac surgery
      is inhibited by interleukin-10 via the Janus kinase (Jak)/signal transducers and
      activator of transcription (STAT) pathway.
AB  - SUMMARY: OBJECTIVES To identify the signaling pathways involved in the anti
      inflammatory shift of the cytokine balance due to hypothermia during
      cardiopulmonary bypass. DESIGN Experimental animal study. SETTING Department of
      experimental surgery of a university hospital. SUBJECTS Young pigs. INTERVENTIONS
      Animals underwent normothermic (37 degrees C) or hypothermic (28 degrees C)
      cardiopulmonary bypass (n = 6 each). Samples of liver tissue were taken before
      and 6 hrs after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS
      Intrahepatic expression of tumor necrosis factor-alpha, interleukin-10, inducible
      nitric oxide synthase, and suppressor of cytokine signaling-3 was detected by
      reverse transcriptase polymerase chain reaction and/or Western blotting.
      Concentrations of the inhibitory protein of nuclear factor-kappaB, IkappaB, and
      of the signal transducer and activator of transcription (STAT)-3 were measured by
      Western blotting. The DNA-binding activity of nuclear factor-kappaB and STAT-3
      was assessed by electrophoretic mobility shift and supershift assays. Liver cell
      necrosis and apoptosis were assessed by histology and terminal deoxynucleotidyl
      transferase-mediated dUTP nick end-labeling assay, respectively. Pigs operated on
      in hypothermia showed significantly higher intrahepatic concentrations of
      interleukin-10 and lower concentrations of tumor necrosis factor-alpha than the
      others. They also showed a lower percentage of hepatic cell necrosis but not of
      apoptosis. This anti-inflammatory reaction observed in the hypothermic group was
      associated with a higher expression of suppressor of cytokine signaling-3 and
      with increased activation of STAT-3. Activation of nuclear factor-kappaB and
      expression of inducible nitric oxide synthase, however, were not significantly
      different between both groups. CONCLUSION Our results show that hypothermia
      during cardiopulmonary bypass up-regulates interleukin-10 via STAT-3 activation,
      which in turn leads to the attenuation of tumor necrosis factor-alpha expression
      and to hepatic protection.

PMID- 14668614
TI  - Apoptosis signal-regulating kinase 1-mediated signaling pathway regulates
      hydrogen peroxide-induced apoptosis in human pulmonary vascular endothelial
      cells.
AB  - OBJECTIVE: Reactive oxygen species initiate pulmonary vascular endothelial cell
      damage leading to an increase in endothelial permeability resulting in the
      production of pulmonary edema. Apoptosis signal-regulating kinase (ASK)-1 is a
      ubiquitously expressed mitogen-activated protein kinase kinase kinase (MAPKKK)
      that activates the MKK3/MKK6-p38 MAPK and the SEK1-c-Jun N-terminal kinase (JNK)
      signaling cascade. ASK1 has been implicated in cytokine- and stress-induced
      apoptosis. However, little is known about the role of ASK1 in apoptosis in
      hydrogen peroxide (H2O2)-stimulated pulmonary vascular endothelial cells and how
      ASK1-mediated apoptosis is executed. To clarify this issue, we examined the role
      of ASK1-p38 MAPK/JNK cascade in apoptosis and caspase-3 activation in H2O2
      stimulated pulmonary vascular endothelial cells. DESIGN: Experimental laboratory
      study. SETTING: University laboratory. SUBJECTS: Normal human pulmonary artery
      endothelial cells. INTERVENTIONS: Western blot analysis and quantification of
      apoptosis in cells. MEASUREMENTS AND MAIN RESULTS: The results showed that H2O2
      induced ASK1 phosphorylation and concomitantly p38 MAPK and JNK phosphorylation
      as well as induced caspase-3 activation in pulmonary vascular endothelial cells.
      To further characterize the role of ASK1 cascade in H2O2-induced apoptosis of
      pulmonary vascular endothelial cells, the dominant negative form of ASK1-stably
      transfected porcine artery endothelial cells was used. p38 MAPK and JNK
      phosphorylation, caspase-3 activation, and apoptosis in the dominant negative
      form of ASK1-stably transfected porcine artery endothelial cells were depressed
      compared with those in the parental porcine artery endothelial cells. CONCLUSION:
      ASK1-p38 MAPK/JNK cascade regulates apoptosis of H2O2-stimulated human pulmonary
      vascular endothelial cells.

PMID- 14668615
TI  - Neurologic intensive care resource use after brain tumor surgery: an analysis of
      indications and alternative strategies.
AB  - OBJECTIVE: Greater demand and limited resources for intensive care monitoring for
      patients with neurologic disease may change patterns of intensive care unit
      utilization. The necessity and duration of intensive care unit management for all
      neurosurgical patients after brain tumor resection are not clear. This study
      evaluates a) the preoperative and perioperative variables predictive of extended
      need for intensive care unit monitoring (>1 day); and b) the type and timing of
      intensive care unit resources in patients for whom less intensive postoperative
      monitoring may be feasible. DESIGN: Retrospective chart review. SETTING: A
      neurocritical care unit of a university teaching hospital. PATIENTS: Patients
      were 158 consecutive postoperative brain tumor resection patients admitted to a
      neurocritical care unit within a 1-yr period (1998-1999). INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Twenty-three patients (15%) admitted to the
      neurocritical care unit for >24 hrs were compared with 135 (85%) patients
      admitted for <24 hrs. Predictors of >1-day stay in the neurocritical care unit in
      a logistic regression model were a tumor severity index comprising radiologic
      characteristics of tumor location, mass effect, and midline shift on the
      preoperative magnetic resonance imaging scan (odds ratio, 12.5; 95% confidence
      interval, 3.1-50.5); an intraoperative fluid score comprising estimated blood
      loss, total volume of crystalloid, and other colloid/hypertonic solutions
      administered (odds ratio, 1.8; 95% confidence interval, 1.2-2.6); and
      postoperative intubation (odds ratio, 67.5; 95% confidence interval, 6.5-702.0).
      Area under the receiver operating characteristic curve for the model of
      independent predictors for staying >1 day in the neurocritical care unit was
      0.91. Neurocritical care unit resource use was reviewed in detail for 134 of 135
      patients who stayed in the neurocritical care unit for <1 day. Sixty-five (49%)
      patients required no interventions beyond postanesthetic care and frequent
      neurologic exams. A total of 226 intensive care unit interventions were performed
      (mean +/- sd, 1.7 +/- 2.6) in 69 (51%) patients. Ninety (67%) patients had no
      further interventions after the first 4 hrs. Neurocritical care unit resource use
      beyond 4 hrs, largely consisting of intravenous analgesic use (72% of orders),
      was significantly associated with female gender, benign tumor on frozen section
      biopsy, and postoperative intubation (chi-square, p <.05). CONCLUSIONS: A small
      fraction of patients require prolonged intensive care unit stay after craniotomy
      for tumor resection. A patient's risk of prolonged stay can be well predicted by
      certain radiologic findings, large intraoperative blood loss, fluid requirements,
      and the decision to keep the patient intubated at the end of surgery. Of those
      patients requiring intensive care unit resources beyond the first 4 hrs, the
      interventions may not be critical in nature. A prospective outcome study is
      required to determine feasibility, cost, and outcome of patients cared for in
      extended recovery and then transferred to a skilled nursing ward.

PMID- 14668616
TI  - Role of functional plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism
      in susceptibility, severity, and outcome of meningococcal disease in Caucasian
      children.
AB  - OBJECTIVE: Meningococcal sepsis invariably is associated with coagulopathy. We
      have previously reported an association between mortality rate in meningococcal
      disease and the functional 4G/5G promoter polymorphism of the plasminogen
      activator-inhibitor (PAI)-1 gene in a small patient cohort. In a much larger
      cohort, we aimed to confirm these results and further investigate the role of the
      4G/5G polymorphism in determining susceptibility, outcome, and complications of
      disease.DESIGN Susceptibility was investigated in two separate studies, a case
      control study and a family-based transmission study, each test using a separate
      patient cohort. Severity was investigated using clinical diagnosis, the presence
      of vascular complications, Pediatric Risk of Mortality (PRISM)-predicted
      morality, and actual mortality. SETTING: University hospital and laboratories.
      SUBJECTS: Subjects were 510 UK pediatric patients, 210 parents of patients, and
      155 UK Caucasian controls. INTERVENTIONS: DNA extraction and 4G/5G PAI-1
      genotyping was carried out using published techniques. MEASUREMENTS AND MAIN
      RESULTS: Predicted mortality distribution differed significantly between
      genotypes (p =.05) with a significantly higher median PRISM in the 4G/4G (41.1%)
      than the 4G/5G (23.4%) and 5G/5G (19.0%) genotyped patients combined (p =.02).
      Actual mortality rate was significantly associated with both genotype (chi-square
      = 14.8, p =.001) and allele frequencies (chi-square = 14.0, p <.0001), with more
      deaths in the 4G/4G (28.4%) than the 4G/5G and 5G/5G genotyped patients combined
      (14.9%; chi-square = 7.9; p =.005; risk ratio, 1.9; 95% confidence interval, 1.2
      3.0). Logistic regression indicated a 40% and 91% reduction in the odds of dying
      if a patient was either 4G/5G or 5G/5G, respectively, in comparison to a 4G
      homozygous patient. When analyzed by clinical diagnosis, the association with
      death was found only in the sepsis group (chi-square = 18.7, p <.0001; risk
      ratio, 2.7; 95% confidence interval, 1.6-4.6). In survivors of disease, a
      significantly higher proportion of 4G/4G patients suffered from vascular
      complications (chi-square = 6.7, p =.03; risk ratio, 2.4; 95% confidence
      interval, 1.1-5.0). The 4G/5G polymorphism was not associated or linked with
      susceptibility (case-control result, p =.6; family-based transmission study
      results, p =.2). CONCLUSIONS: This study confirms that Caucasian pediatric
      patients carrying the functional PAI-1 4G/4G genotype are at an increased risk of
      developing vascular complications and dying from meningococcal disease.

PMID- 14668617
TI  - Poisonings and overdoses in the intensive care unit: general and specific
      management issues.
AB  - OBJECTIVE: To provide current information on general and specific interventions
      for overdoses likely to require intensive care. DESIGN: Review of literature
      relevant to selected interventions for general management of overdoses and
      specific poisons. RESULTS: The benefit of interventions to decrease absorption or
      enhance elimination of toxins is limited to a relatively small number of specific
      agents. Antidotes and certain interventions may be helpful in preventing or
      treating toxicity in specific poisonings when used appropriately. Intensive
      supportive care is also necessary to achieve good outcomes. CONCLUSION: Knowledge
      of the indications and limitations of current interventions for poisonings and
      overdoses is important for care of the critically ill poisoned patient.

PMID- 14668618
TI  - Positive end-expiratory pressure or prone position: is that the question?

PMID- 14668619
TI  - Prone position, carbon dioxide elimination, and survival: a turn for the better?

PMID- 14668620
TI  - Who benefits from pulmonary artery catheterization?

PMID- 14668621
TI  - Improving survival for sepsis: on the cutting edge.

PMID- 14668622
TI  - Look before you leap.

PMID- 14668623
TI  - Intensive care unit admissions do not pass the reasonableness test.

PMID- 14668624
TI  - Hypothermia: cooling down inflammation.

PMID- 14668625
TI  - In meningococcal disease 4G bad, 5G good.

PMID- 14668626
TI  - Prone position: not yet justified in neurologic injury.

PMID- 14668630
TI  - Overview of the State of the Art Expert Meeting of the Intercontinental Childhood
      ITP Study Group (ICIS).

PMID- 14668627
TI  - Maleimide-polyethylene glycol-modified human hemoglobin.

PMID- 14668631
TI  - The etiology of childhood immune thrombocytopenic purpura: how complex is it?
AB  - Recent developments in genomics and basic immunology have provided a new set of
      tools for investigation into the etiology and treatment of childhood immune
      thrombocytopenia purpura (ITP). The genomic revolution is generating a catalog of
      germ-line common genetic variants, some of which could influence the
      susceptibility or outcome of ITP. Similarly, in vitro analyses and animal models
      have been employed to probe the basic alterations underlying ITP. The emergence
      of a more refined understanding of complex diseases such as ITP has important
      implications for prevention, therapy, and follow-up. The relative contribution of
      the genetic component and its interaction with the strong environmental stimulus,
      such as an acute, antecedent viral infection, remains to be determined.

PMID- 14668632
TI  - Pathogenic T-cell responses in patients with autoimmune thrombocytopenic purpura.
AB  - Autoimmune thrombocytopenic purpura (AITP) is a bleeding disorder in which
      autoantibodies are directed against an individual's own platelets, leading to
      enhanced clearance through Fc receptor (R)-mediated phagocytosis by macrophages
      residing in the reticuloendothelial system, particularly in the spleen. This
      review surveys the recent current literature and updates our understanding of the
      cell-mediated immunology of AITP. It will focus on the relationship between T
      cell reactivities and cytokine profiles in patients with AITP. Understanding
      these cellular immune aspects of AITP is vital for developing antigen-specific
      immunotherapies to treat the disease.

PMID- 14668633
TI  - Role of Fcgamma receptors in the pathogenesis and treatment of idiopathic
      thrombocytopenic purpura.
AB  - Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized
      by autoantibody-mediated platelet destruction. Platelets with associated IgG are
      targeted for destruction by phagocytic cells bearing Fc receptors in the
      reticuloendothelial system. While there are a variety of therapeutics available
      for this incompletely understood disease, one of the treatments of choice is
      infusion of intravenous immunoglobulin (IVIG). This review will discuss the
      pathophysiology of ITP with an emphasis on the role of Fcgamma receptors in both
      the pathogenesis and treatment of the disease by IVIG. Other prominent theories
      of the mechanisms of action of IVIG, including the role of anti-idiotype
      antibodies, will also be addressed.

PMID- 14668634
TI  - Platelet function and immune response.
AB  - Altered platelet function may cause abnormal bleeding tendency or thrombosis. The
      goal of this article is to provide insights for understanding how platelet
      functions are related to immune response. Autoantibodies and drug-induced
      platelet antibodies have been demonstrated to downregulate or enhance platelet
      function. Drug-induced immune thrombocytopenia is an important adverse effect of
      glycoprotein IIb/IIIa antagonists. Platelets respond to binding of glycoprotein
      IIb/IIIa by partial platelet activation. This includes conformational changes of
      glycoprotein IIb/IIIa. Membrane changes may expose immunogenic neoantigens
      capable of abnormally altering immune responses. The presence of drug-dependent
      antibodies in an unexpectedly high frequency compared with the frequency of overt
      thrombocytopenia has opened a model for further studies. These may include
      monitoring of antiplatelet immune responses when new platelet antagonists are
      developed and comparisons of specific immune responses in other acute
      thrombocytopenias, such as those induced by quinidine or heparin and that
      associated with gold therapy or in acute profound thrombocytopenia, which may
      follow vaccination with live attenuated viruses.

PMID- 14668635
TI  - Investigation and management of newly diagnosed childhood idiopathic
      thrombocytopenic purpura: problems and proposed solutions.
AB  - The purpose of this paper is to describe current problems in investigation and
      management of newly diagnosed childhood idiopathic thrombocytopenic purpura
      (ITP). An Intercontinental Childhood ITP Study Group was established in 1997 with
      the aim to promote international clinical research based on a research
      environment and network of physicians. Initial and still ongoing projects include
      registries to collect data on the natural history of ITP, demographics of
      patients with ITP, and its management. Registry I was successful, with data on
      almost 3,000 patients from 38 countries. Registry II investigates the occurrence
      and severity of bleeding at the time of diagnosis and within 2 years of follow
      up. Current problems are listed and discussed. An international network of
      physicians similar to that of malignant diseases for the conduct of clinical
      research and regular scientific meetings is the basis for solutions of the
      identified problems.

PMID- 14668636
TI  - Childhood chronic immune thrombocytopenic purpura: unresolved issues.
AB  - Chronic immune thrombocytopenic purpura (ITP), defined as a platelet count of
      below 150 x 109/L persisting for more than 6 months from onset of illness, occurs
      in approximately 20% to 25% of children with acute-onset ITP. A small subset of
      these patients (approximately 5%) will manifest symptomatic, severe
      thrombocytopenia (platelet counts <20 x 109/L) at 1 year or longer following
      diagnosis, and may require splenectomy. Complete/partial response rates following
      splenectomy in children with primary chronic ITP are of the order of 70% to 75%;
      response rates are lower in children with secondary ITP and those with complex
      autoimmune cytopenias (e.g., Evans syndrome). Laparoscopic splenectomy is
      increasingly preferred over open splenectomy. Patients should be immunized with
      the pneumococcal, Haemophilus type b and meningococcal vaccines before
      splenectomy; the duration of postsplenectomy antibiotic prophylaxis using
      penicillin or an equivalent antibiotic is controversial but should be at least
      until 5 years of age and for a minimum of 1 year postsplenectomy. Some experts
      advocate life-long antibiotic prophylaxis. Treatment of postsplenectomy failures
      is a challenge; partial/complete remission rates are low, and multimodality
      therapy may be more efficacious than monotherapy. The presence of an accessory
      spleen should be sought and removal considered if present. The role of newer
      treatment modalities such as anti-CD 20 remains to be established.

PMID- 14668637
TI  - Idiopathic thrombocytopenic purpura in adults.
AB  - Immune thrombocytopenic purpura (ITP) is an organ-specific autoimmune disorder in
      which platelets opsonized by antiplatelet antibodies are destroyed by the
      reticuloendothelial system. As a result the peripheral blood platelet count is
      low; if sufficiently severe, it may lead to bruising and mucocutaneous bleeding.
      The disorder may occur in adults and in children; in the former the disease
      affects primarily females, whereas the childhood type affects the sexes equally.
      For most individuals the disorder is minor, requiring little treatment, but
      patients with more severe forms of the disease require therapy to elevate the
      platelet count to a safe level to prevent serious bleeding. Therapies include
      corticosteroids, intravenous immunoglobulin, splenectomy, and immunosuppressive
      agents. Because there have been few trials in ITP, there is little evidence to
      guide treatment, and all the treatments may have adverse effects in terms of
      morbidity and mortality. The American Society of Hematology and British Committee
      for Standards in Haematology guidelines provide a framework for management but
      nonetheless are based on little evidence. In this paper the authors review the
      management of ITP in adults, children, and pregnant women and highlight some of
      the novel therapies being explored in this disorder, in addition to some of the
      ongoing laboratory research exploring the mechanisms underlying the disease.

PMID- 14668638
TI  - Alloimmune thrombocytopenias.
AB  - Alloimmunization against platelet antigens may take place during pregnancy and
      following transfusion or transplantation. The resulting antibodies bind to the
      target platelet antigens and may lead to a rapid sequestration of incompatible
      platelets. The alloimmune thrombocytopenias are classified into neonatal
      alloimmune thrombocytopenia, post-transfusion purpura, passive alloimmune
      thrombocytopenia, transplantation-associated alloimmune thrombocytopenia, and
      platelet transfusion refractoriness. Neonatal alloimmune thrombocytopenia occurs
      in roughly one of 1,000 births and is the most important type in children. The
      management of affected infants during pregnancy is yet not established, and the
      most rapidly effective treatment after delivery is the transfusion of compatible
      platelets.

PMID- 14668639
TI  - Bleeding signs in children with idiopathic thrombocytopenic purpura.
AB  - Too little emphasis has been placed upon bleeding signs in children with
      idiopathic thrombocytopenic purpura (ITP). The frequency, location, and severity
      of clinical bleeding should dominate management considerations and the actual
      platelet count should be de-emphasized. With the notable exception of
      intracranial bleeding, virtually all prior literature reports describing case
      series or randomized trials of ITP have not addressed or even mentioned bleeding
      signs in study subjects. Future clinical investigations in childhood ITP should
      include a careful description of bleeding manifestations in the study populations
      and should assess outcome in terms of bleeding signs, quality of life, toxicity
      of therapy, cost, and, incidentally, the platelet count.

PMID- 14668640
TI  - Severe bleeding in idiopathic thrombocytopenic purpura.
AB  - Immune thrombocytopenia in childhood is usually an acute self-limiting disorder
      and despite very low platelet counts is rarely complicated by serious bleeding.
      Several surveys indicate that only 5% or fewer children experience serious
      bleeding, most commonly from the nose or gastrointestinal tract. Such children
      need urgent measures to control bleeding, both transfusion where necessary and
      pharmacotherapy to raise the platelet count. Not infrequently the response of the
      count is less than optimal. While intracranial hemorrhage is the most feared and
      serious complication, it is rare, occurring in about 0.3% of cases, and if
      treated promptly usually has a good outcome. Treatment prior to intracranial
      hemorrhage does not necessarily prevent it, and it may occur after many months of
      otherwise clinically mild disease. The relative risk increases with the length of
      time a child has a very low platelet count. An international registry will help
      to collect more information about these important cases. Menstrual bleeding can
      cause severe problems for adolescents and may need a multidisciplinary approach
      with hormonal manipulation of the menstrual cycle.

PMID- 14668641
TI  - Mechanisms of action of therapeutics in idiopathic thrombocytopenic purpura.
AB  - Idiopathic thrombocytopenic purpura (ITP) is a common immune disorder caused by
      platelet-reactive autoantibodies. Antibody-coated platelets are cleared more
      rapidly from the circulation, often in the spleen, than they can be replaced by
      compensatory stimulation of platelet production in the bone marrow. In some
      patients, platelet production is depressed as well. ITP in adults does not
      generally remit spontaneously, and most patients require treatment to prevent
      bleeding at one time or another. Therapy with corticosteroids, danazol,
      intravenous immune globulin, anti-D antibody, and several other agents inhibits
      clearance of the antibody-coated platelets but is rarely curative. Most patients
      will sustain a hemostatic response after splenectomy, although relapses may occur
      at any time. Patients may be more responsive to these same modalities after
      splenectomy, but treatment with an immunosuppressant that inhibits T- and B-cell
      function and cooperation, including azathioprine, cyclophosphamide, cyclosporine,
      mycophenolate mofetil, or anti-CD20, may be required. Antiviral therapy is useful
      in patients with HIV or hepatitis C infection, but no consensus has been reached
      as to the efficacy of antibiotics to eradicate Helicobacter pylori. Promising
      results have been seen in several patients treated with a modified
      thrombopoietin. It may be possible to design therapeutics that exploit the
      apparent restricted immunoglobulin gene usage by antiplatelet antibodies, perhaps
      in the form of engineered anti-idiotypic antibodies or other compounds that
      specifically target autoantibody-producing B cells. Rationale therapy awaits a
      more thorough understanding of autoantibody production.

PMID- 14668642
TI  - Antiplatelet antibodies in chronic adult immune thrombocytopenic purpura: assays
      and epitopes.
AB  - Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder
      characterized by thrombocytopenia due to autoantibody-induced platelet
      destruction. The majority of these autoantibodies are directed to epitopes on
      either glycoprotein (GP) IIb-IIIa or GPIb-IX. The newer antigen-specific
      autoantibody assays are capable of detecting both platelet-associated and plasma
      autoantibodies and have a definite role in the diagnosis of immune
      thrombocytopenia. A positive assay provides strong evidence for the presence of
      immune thrombocytopenia both in chronic ITP and in other diseases where immune
      thrombocytopenia may occur, such as collagen vascular disease and
      lymphoproliferative disorders. However, a negative assay does not rule out the
      presence of ITP. Somewhat concerning is the large number of patients who have
      negative assays. Several possible explanations for these observations are
      discussed. Recent studies have localized some ITP autoepitopes to specific
      regions of GPIIb-IIIa and GPIb-IX. Most autoepitopes on GPIIb-IIIa are
      conformational, in view of their dependence on divalent cations, and are
      localized to the N-terminal portion of GPIIb, while the GPIb-IX autoepitopes that
      have been identified are localized to GPIb amino acids 333-341.

PMID- 14668643
TI  - Using decision analysis techniques to deal with "unanswerable" questions in
      idiopathic thrombocytopenic purpura.
AB  - Idiopathic thrombocytopenic purpura (ITP) is a common disorder with rare adverse
      outcomes. This makes it a particularly difficult area in which to undertake
      conventional studies. An alternative method for solving clinical questions is
      decision analysis, which is in essence a computer-assisted synthesis of the
      literature. Using the example of a newly diagnosed ITP patient, the author
      attempts to answer the question of whether a bone marrow aspirate (BMA) is
      required prior to starting steroids. Using decision analysis methodology, the
      author determines that BMA is not essential prior to starting steroids. More
      importantly, three variables critical to the decision-making process are
      determined: the risk of death from the BMA procedure, the altered chance of
      survival for a patient with acute lymphoblastic leukemia (ALL) inappropriately
      given steroids, and how sensitive the complete blood count is at determining the
      risk of ALL. This scenario demonstrates the value of decision analysis and lays
      the groundwork for future endeavors.

PMID- 14668644
TI  - Quality of life in children and families with bleeding disorders.
AB  - Quality of life (QoL) in children and adolescents with bleeding disorders and
      their families is a relatively new topic. It is important to understand more
      about QoL in this patient population to evaluate and if necessary to improve the
      care patients receive. To achieve this aim, a questionnaire to assess patients'
      QoL in hemophilia was developed and psychometrically tested. Three hundred twenty
      hemophiliac children and adolescents from six European countries and their
      families were asked to fill out a questionnaire regarding different aspects of
      their well-being and functioning, as well as their views on hemophilia care.
      Generic QoL questionnaires showed that children with hemophilia have a higher QoL
      than other patients with chronic disease, such as asthma/atopic dermatitis and
      obesity. Several determinants affected patients' QoL (e.g., number of bleeds,
      social support). Parents' and children's assessments differed with regard to
      social and emotional aspects of QoL. The study showed that variations in QoL can
      be explained by clinical and psychosocial factors and suggested that QoL can be
      assessed and enhanced both by medical and non-medical (e.g., psychological)
      interventions.

PMID- 14668645
TI  - Local and cultural aspects of childhood idiopathic thrombocytopenic purpura: a
      summary of statements from the 12 countries worldwide.
AB  - Idiopathic thrombocytopenic purpura (ITP) is a heterogeneous bleeding disorder.
      The Intercontinental Childhood ITP Study Group (ICIS) analyzed demographic data
      and outcome in a prospective registry of over 2,000 children with ITP. In
      addition, participating centers from 12 different countries worldwide were asked
      to describe their local and cultural aspects of ITP management to provide a
      summary statement of the variable diagnostic and management approaches for
      childhood ITP. The statements of the 15 reports from 12 countries are summarized
      under eight main areas to reflect the variability in approach to ITP among
      different countries. The management of ITP in children differs dramatically
      worldwide in terms of observation only, medical treatment, bleeding symptoms,
      acceptable platelet counts, need for hospitalization or outpatient treatment, and
      medical care climate. The majority of experimental treatments, surveys, and
      guidelines are not evidence-based. Although there is a great need for cooperative
      studies to learn more about diagnosis, management, and prognosis in the
      heterogeneous disorder of ITP, local and cultural variations must be considered
      in international investigations.

PMID- 14668646
TI  - New developments in idiopathic thrombocytopenic purpura (ITP): cooperative,
      prospective studies by the Intercontinental Childhood ITP Study Group.
AB  - Based on 6 years of experience with worldwide cooperation of investigators in the
      field of hematology, the International Childhood ITP Study Group (ICIS) has
      provided a long-term concept for prospective studies and new, evidence-based
      definitions of idiopathic thrombocytopenic purpura (ITP). Structured interactions
      between the cooperating investigators, the ICIS board, the writing committees, an
      expert panel, and the central operative office are summarized in the Rules of the
      ICIS. Preliminary experience shows high acceptance of the activities of the ICIS
      by participants from many countries. There is good cooperation, resulting in
      analyses and publication of results. New areas of focus for ICIS include the
      formation of an expert panel, regular meetings, and publication of results from
      current studies. Long-term financial resources must be found. ICIS is looking
      back on 6 constructive years of international cooperation resulting in new or
      confirmatory evidence regarding the demographics, diagnosis, natural history, and
      management of childhood ITP. New structures and cooperation must be identified to
      continue this productive endeavor.

PMID- 14668647
TI  - ITP: an overview of the conference and future directions with an abbreviated ITP
      history.

PMID- 14668648
TI  - Complementary and alternative medicine: is it just a case of more tools for the
      medical bag?

PMID- 14668649
TI  - Research methodology: implications for CAM pain research.
AB  - The National Cancer Institute's Office of Cancer Complementary and Alternative
      Medicine established a series of expert panels to develop the state of the
      science in research methodologies in CAM cancer research. Panelists from both
      conventional and CAM research draw on their expertise in their relative fields to
      apply their knowledge and expertise to specific topic areas within cancer CAM.
      The first panel is focused on cancer symptom research. The discussion and
      conclusions raised by this panel primarily address pain research but are
      applicable to other symptoms as well. This article will focus on the panel
      presentations that are most applicable to CAM pain research in both cancer and
      noncareer pain populations, identifying the major challenges and conclusions
      offered by the panelists.

PMID- 14668650
TI  - Manual therapies for pain control: chiropractic and massage.
AB  - OBJECTIVES: To evaluate the effectiveness of chiropractic and massage therapy for
      the reduction of any type of pain. METHODS: Systematic reviews of chiropractic
      and massage as a means of pain control were located and evaluated. RESULTS: Six
      systematic reviews were found, 4 of chiropractic and 2 of massage therapy.
      Promising evidence emerged from some of these reviews but neither for
      chiropractic nor for massage was there fully convincing evidence for
      effectiveness in controlling musculoskeletal or other pain. DISCUSSION: The
      notion that chiropractic or massage are effective interventions for pain control
      has not been demonstrated convincingly through rigorous clinical trials.

PMID- 14668651
TI  - Selected CAM therapies for arthritis-related pain: the evidence from systematic
      reviews.
AB  - OBJECTIVES: The purpose is to examine what is known about the efficacy of
      selected complementary and alternative medicine (CAM) therapies for pain from
      arthritis and related conditions based on systematic reviews and meta-analyses.
      METHODS: Results specifically related to pain were retrieved from review articles
      of acupuncture, homeopathy, herbal remedies, and selected nutritional
      supplements. RESULTS: Evidence exists to support the efficacy of reducing pain
      from osteoarthritis (OA) for acupuncture; devil's claw, avocado/soybean
      unsaponifiables, Phytodolor and capsaicin; and chondroitin, glucosamine, and
      SAMe. Strong support exists for gamma linolenic acid (GLA) for pain of rheumatoid
      arthritis (RA). CONCLUSIONS: Despite support for some of the most popular CAM
      therapies for pain from arthritis-related conditions, additional high quality
      research is needed for other therapies, especially for herbals and homeopathy.

PMID- 14668652
TI  - Dietary constituents as novel therapies for pain.
AB  - The use of complementary and alternative medicine has dramatically increased in
      the United States. The effects of select dietary constituents in animal models
      and clinical pain states are reviewed. Specifically, the antinociceptive and
      analgesic properties of soybeans, sucrose, and tart cherries are discussed. The
      potential actions of dietary constituents as antiinflammatory and antioxidant
      agents are presented.

PMID- 14668653
TI  - Mind-body therapies for the management of pain.
AB  - This paper reviews the evidence for mind-body therapies (eg, relaxation,
      meditation, imagery, cognitive-behavioral therapy) in the treatment of pain
      related medical conditions and suggests directions for future research in these
      areas. Based on evidence from randomized controlled trials and in many cases,
      systematic reviews of the literature, the following recommendations can be made:
      1) multi-component mind-body approaches that include some combination of stress
      management, coping skills training, cognitive restructuring and relaxation
      therapy may be an appropriate adjunctive treatment for chronic low back pain; 2)
      multimodal mind-body approaches such as cognitive-behavioral therapy,
      particularly when combined with an educational/informational component, can be an
      effective adjunct in the management of rheumatoid and osteoarthritis; 3)
      relaxation and thermal biofeedback may be considered as a treatment for recurrent
      migraine while relaxation and muscle biofeedback can be an effective adjunct or
      stand alone therapy for recurrent tension headache; 4) an array of mind-body
      therapies (eg, imagery, hypnosis, relaxation) when employed pre-surgically, can
      improve recovery time and reduce pain following surgical procedures; 5) mind-body
      approaches may be considered as adjunctive therapies to help ameliorate pain
      during invasive medical procedures.

PMID- 14668654
TI  - Levetiracetam in the treatment of neuropathic pain: three case studies.
AB  - CASE REPORTS: A 55-year-old woman presented with numbness and pain in both lower
      extremities. The pain was of sudden onset and of 4 months' duration. A nerve
      conduction study demonstrated a bilateral sensorimotor peripheral neuropathy with
      axonal and demyelinating features of a mild degree. Initial treatment with oral
      thiamine and topiramate had little efficacy and caused unacceptable side effects.
      A switch to 1500 mg bid levetiracetam plus nortriptyline resulted in a 60%
      improvement in pain symptoms. A 75-year-old man presented with numbness in both
      feet of 5 years' duration. The sensation of numbness had progressed to persistent
      pain, resulting in sleep disruption. The patient's use of oral thiamine did not
      lead to pain relief, but the addition of 500 mg levetiracetam once in the evening
      led to a complete resolution of his pain and to sleep improvement. A 67-year-old
      obese male was referred from a podiatrist with progressive dysfunction in both
      lower extremities that developed over a 1-year period. Walking more than a few
      steps resulted in sharp, shooting pain that at night disrupted sleep. A nerve
      conduction study demonstrated a severe bilateral sensorimotor peripheral
      neuropathy with axonal and demyelinating features. Treatment with 1000 mg
      levetiracetam bid resulted in complete absence of pain. CONCLUSIONS: In these 3
      case studies, levetiracetam was demonstrated to be an effective therapy in the
      treatment of neuropathic pain. It has the benefits of a low incidence of adverse
      events and an improvement in patients' sleep.

PMID- 14668655
TI  - Health care providers' attitudes and beliefs towards common low back pain: factor
      structure and psychometric properties of the HC-PAIRS.
AB  - OBJECTIVE: The factor structure, reliability and validity of the Health Care
      Providers' Pain and Impairment Relationship Scale (HC-PAIRS) were determined in
      the current study. Furthermore, the ability of the HC-PAIRS to serve as a
      predictor for work and activity recommendations of paramedical health care
      providers was examined. DESIGN: For the current study, 156 therapists from
      several paramedical disciplines (mostly physiotherapy, manual therapy,
      chiropractic, and McKenzie) completed the HC-PAIRS and questionnaires measuring
      the perceived harmfulness of physical activities. Furthermore, the therapists
      gave recommendations for work and physical activity for patients described in
      vignettes. Since a factor structure was already known for the HC-PAIRS a
      confirmatory factor analysis was carried out. Reliability of the HC-PAIRS was
      determined by computing Cronbach's alpha. Validity was examined by reviewing
      associations between scores on the HC-PAIRS and scores on measures of the
      harmfulness of physical activities and recommendations for work and physical
      activity. Regression analyses were carried out to determine whether scores on the
      HC-PAIRS were a predictor of recommendations for work and physical activity while
      controlling for other variables. RESULTS: In contrast to previous research,
      factor analysis revealed only 1 factor and suggested that 2 items should be
      removed from the HC-PAIRS. This factor had a Cronbach's alpha of 0.84. The HC
      PAIRS showed adequate validity. All associations between scores on the HC-PAIRS
      and scores on measures of the harmfulness of physical activities and
      recommendations for work and physical activity were in the expected directions
      and ranged between 0.25 and 0.62 (P < 0.01). Scores on the HC-PAIRS were the only
      significant predictor of recommendations for work and physical activity when
      controlling for possible confounders including gender, years of experience in the
      treatment of back pain, judgments of severity of symptoms, and judgments of
      severity of pathology. CONCLUSION: The HC-PAIRS appears to be a reliable and
      valid measure of health care providers' attitudes and beliefs about the
      relationship between pain and impairment. The role of health care providers'
      attitudes in the treatment of low back pain is discussed.

PMID- 14668656
TI  - The attitudes and beliefs of physiotherapy students to chronic back pain.
AB  - OBJECTIVES: To describe the attitudes and beliefs of physiotherapy students to
      chronic low back pain (LBP) and to investigate whether these attitudes change
      following exposure to a teaching module on chronic back pain. Also, to
      investigate the effect of current or previous LBP on student attitudes and
      beliefs. METHODS: Six hundred and eighteen third and fourth year undergraduate
      physiotherapy students completed the Health Care Providers' Pain and Impairment
      Relationship Scale (HC-PAIRS), 305 of these completing a further scale following
      exposure to a specialized teaching module about chronic back pain. The scale
      contains 15 statements that attribute patients' impairment and disability to
      pain. The student marked on a Likert scale how strongly they agreed with each
      item, with possible scores varying from 15-105. RESULTS: The mean HC-PAIRS scores
      for Year 3 physiotherapy students in 1998, 1999, and 2000 were 54.2 (SD = 8.7),
      55 (SD = 9.4), and 50.9 (SD = 9.3) respectively. The mean HC-PAIRS score for Year
      4 physiotherapy students in 1998 was 52 (SD = 8.9). There was no difference in HC
      PAIRS scores between subjects with and without a history of LBP (HC-PAIRS score
      50.5 vs. 50.0 P = 0.4). There was a significant difference between the before and
      after teaching scores for Year 3 students surveyed immediately following the
      teaching module (1998 Year 3 cohort, mean difference -6.6, 95% CI -8.6 to -4.5,
      2000 Year 3 cohort, mean difference -7.7, 95% CI -10.9 to -4.6); however this
      result needs to be viewed with caution due to the number of students unable to be
      followed up. DISCUSSION: These results suggest that the attitudes and beliefs of
      third year physiotherapy students not exposed to teaching are similar to those of
      community providers. There is no difference between students with and without a
      history of LBP.

PMID- 14668657
TI  - An anatomic study of the sacral hiatus: a basis for successful caudal epidural
      block.
AB  - STUDY DESIGN: An anatomic study of the sacral hiatus using isolated sacra.
      OBJECTIVES: To clarify the anatomic variations of the sacral hiatus using the
      bony landmarks of the sacrum for improving the reliability of caudal epidural
      block (CEB). BACKGROUND DATA: The CEB has been widely used for the diagnosis and
      treatment of lumbar spinal disorders. The reliability of CEB is 70%-80% in the
      literatures. The cause of failure of CEB may depend on anatomic basis. METHODS: A
      total of 92 isolated sacra were used in this study. The bony landmarks were
      sacral hiatus and sacral cornua. Morphologic types of the sacral hiatus were
      classified using these landmarks. Also, location of the apex of sacral hiatus,
      diameter of the sacral canal at the apex of sacral hiatus, and the distance
      between bilateral cornua were measured. Two orthopedic surgeons performed
      measurements independently. RESULTS: Forty-two percent of the cases have both
      hiatus and cornu. Four percent of the cases showed the absent hiatus. The apex of
      sacral hiatus existed at the level of S4 vertebrae in 64% of the cases. The
      average diameter of the sacral canal was 6.0 +/- 1.9 mm. The average distance of
      bilateral sacral cornua was 10.2 +/- 0.35 mm. There were closed hiatus in 3% of
      cases. CONCLUSIONS: The sacral hiatus has anatomic variations. Understanding of
      these variations may improve the reliability of CEB.

PMID- 14668658
TI  - A randomized controlled trial of radiofrequency denervation of the ramus
      communicans nerve for chronic discogenic low back pain.
AB  - OBJECTIVE: The objective of this study was to determine the efficacy of
      percutaneous radiofrequency (RF) thermocoagulation of the ramus communicans nerve
      in patients suffering from chronic discogenic low back pain. METHODS: Forty-nine
      patients who suffered chronic discogenic low back pain at only 1 painful
      vertebral level, and whose pain continued after undergoing intradiscal
      electrothermal annuloplasty (IDET), were randomly assigned to 1 of 2 treatment
      groups. The lesion group (n = 26) received RF thermocoagulation of the ramus
      communicans nerve. Patients in the control group (n = 23) received an injection
      of lidocaine without radiofrequency. Visual analog scale (VAS) pain scores,
      analgesic requirements, SF-36 subscales, and the overall patient satisfaction
      with the procedure were tabulated. RESULTS: The average follow-up period was 4
      months. The patient-reported VAS pain scores were significantly lower (P < 0.05)
      in the lesion group. The scores of the RF lesion group improved by a mean
      increase of 11.3 points (P < 0.05) on the SF-36 bodily pain subscale, and by a
      mean increase of 12.4 points on the physical function subscale (P < 0.05). In a
      follow-up analysis within the RF lesion group, VAS pain scores improved by a mean
      reduction of 3.32 (P = 0.001). The scores improved by a mean increase of 14.5
      points (P = 0.005) on the SF-36 bodily pain subscale and 15.2 points(P = 0.002)
      on the physical function subscale within the RF lesion group. One patient in the
      lesion group complained of mild lower limb weakness, but he completely recovered
      at postoperative 15 days without any serious problems. DISCUSSION: In patients
      with chronic discogenic low back pain, percutaneous RF denervation of the ramus
      communicans nerve should be considered as a treatment option.

PMID- 14668659
TI  - Don't give up, don't ever give up: success is a choice.

PMID- 14668660
TI  - A review of laparoscopic ureteral injury in pelvic surgery.
AB  - The objective of this study was to review the body of literature in reference to
      ureteral injury during laparoscopic surgeries and to determine: 1) the reported
      rates of ureteral injury; 2) the initial laparoscopic surgeries during which
      ureteral injury occurred; 3) the time of injury recognition (intra- versus
      postoperative); 4) the type, 5) the location, and 6) the mode of injury repair;
      and 7) the surgical laparoscopic instruments involved in ureteral injury. The
      appropriate medical subject heading (MSH) terms were selected and used in a
      search of the Medline computerized database and the online American College of
      Obstetricians and Gynecologists database. World literature published in the
      English language on ureteral injury during laparoscopic surgery between 1966 and
      2003 was reviewed.A total of 70 reported instances of ureteral injury during
      laparoscopic surgery were identified among 2491 reported cases in which ureteral
      laparoscopic complications were discussed. Incidences of injury ranged from <1%
      to 2%. These 2491 cases of laparoscopy were presented as a mixed group, which
      included case reports, small series of studies, as well as longer, consecutive
      studies. In 18 of the 70 (25.7%) cases, the initial laparoscopic procedures
      during which ureteral injury occurred were not described or specified. In cases
      in which the type of laparoscopic surgery was specified, 14 of the 70 (20.0%)
      total cases of ureteral injury occurred during laparoscopically assisted vaginal
      hysterectomy (LAVH). Ureteral injury was identified intraoperatively in 6 of 70
      (8.6%) cases, postoperatively in 49 of 70 (70.0%) cases, and, in 15 of 70 (21.4%)
      cases, the time of diagnosis was not specified. In 36 of the 70 (51.4%) reported
      injuries, the type of injury was not specified or described. In instances in
      which the types of injury were described, transection occurred most commonly,
      accounting for 14 of 70 (20.0%) injuries. The location of ureteral injury was not
      specified in 46 of the 70 (65.7%) cases. When location was specified, injuries
      most often occurred at or above the pelvic brim, accounting for 10 of the total
      70 (14.3%). Electrocautery was involved in 17 of the 70 (24.3%) cases of ureteral
      injury, but in 34 of the 70 (48.6%) cases, the surgical laparoscopic instrument
      involved was not reported. A laparotomy was used to repair the ureteral injury in
      43 of 70 (61.4%) cases.Ureteral injuries reported in peer-reviewed journals often
      lack detailed presentation of the initial laparoscopic surgeries during which
      ureteral injury occurred, or of the type, the location, and the instrumentation
      involved in ureteral injury. A high incidence of ureteral injury was found among
      the laparoscopic procedures analyzed in this review. Laparoscopically-assisted
      vaginal hysterectomy was the leading procedure in which injury occurred, and
      instruments involved in electrocoagulation were associated with the most injuries
      incurred during laparoscopic surgery.

PMID- 14668661
TI  - Labor analgesia for the parturient with an uncommon disorder: a common dilemma in
      the delivery suite.
AB  - There appears to be an absence of uniform guidelines for management of labor
      analgesia in pregnant patients with uncommon medical conditions such as Marfan's
      syndrome, Ehlers-Danlos syndrome, achondroplastic dwarfism, previous back
      surgery, and kyphoscoliosis. A Medline search for articles highlighting
      considerations for obstetric anesthesia in parturients with these disorders was
      performed. Because of the multiorgan involvement and varied presentations of
      these disorders, no uniform or routine obstetric anesthetic recommendations can
      be made. In the absence of uniform obstetric anesthesia guidelines for pregnant
      patients with Marfan's syndrome, Ehlers-Danlos syndrome, achondroplastic
      dwarfism, previous back surgery, and kyphoscoliosis, the decision whether to
      administer regional anesthesia (epidural labor analgesia) should be based on an
      individual risk-to-benefit ratio on a case-by-case basis.

PMID- 14668662
TI  - Levels of alpha-fetoprotein during pregnancy and early infancy in normal and
      disease states.
AB  - Alpha-fetoprotein (AFP) was 1 of the first serum protein markers to serve in the
      dual capacities of tumor marker and fetal defect marker, ie, an oncofetal
      protein, in the clinical laboratory. Although the serum-marker capacity of AFP
      has long been used, less is known of the fluid compartments of this oncofetal
      protein during fetal and perinatal development. In this review, the biologic
      activities of AFP are discussed in light of its presence in the various biologic
      fluid compartments: fetal serum, amniotic fluid, cord blood, urine, and maternal
      serum. AFP concentrations within the biologic fluids are considered in the
      context of gestational age, sex, body weight, and anatomic location. Discussion
      follows concerning the relationships and roles of AFP in various developmental
      disorders such as hypothyroidism, folate deficiencies, autoimmune disorders,
      acquired immunodeficiency disorder (AIDS), congenital heart defects, cystic
      fibrosis, preeclampsia/hypertension, and platelet aggregation disorders. Based on
      its presence in so many types of birth defects, malformations, and congenital
      anomalies, AFP can be seen to serve as a form of molecular "duct tape" during
      pregnancy and postnatal development.

PMID- 14668663
TI  - The association between profit levels and quality of care in California nursing
      homes.

PMID- 14668664
TI  - Quality of care in nursing homes: an analysis of relationships among profit,
      quality, and ownership.
AB  - BACKGROUND: Recent work has highlighted a negative correlation between
      proprietary status and nursing home quality of care. This relationship might be
      explained by the context in which proprietary homes operate. However, another
      possible explanation is that some proprietary homes take excessive profit to the
      detriment of care quality. OBJECTIVE: To examine the relationship between profit
      levels and quality in proprietary and nonproprietary nursing homes (NHs),
      accounting for resident and market characteristics. METHODS: Data on 1098 free
      standing NHs were taken from the California Office of Statewide Health Planning
      and Development, the On-line Survey Certification and Reporting System, and
      California licensing and statistical reports for 1998 and 1999. Tobit
      multivariate techniques were used to examine the relationship between deficiency
      citations and a range of explanatory variables, including profit. RESULTS:
      Proprietary homes in California had significantly lower quality of care than
      nonproprietary homes. A stratified analysis revealed that, controlling for
      resident, facility, and market characteristics, profits located within the
      highest 14% of the proprietary sector's profit distribution were associated with
      significantly more total deficiencies and serious deficiencies. This relationship
      was not found in nonproprietary facilities. Other factors related to deficiencies
      included the ethnic mix of residents and facility size. CONCLUSIONS: Within the
      context in which proprietary homes operate, profit above a given threshold is
      associated with a higher number of deficiencies. Given this and the role of the
      proprietary sector in NH care, careful monitoring of profit levels in this sector
      appears warranted.

PMID- 14668666
TI  - Assessing the effect of Taiwan's outpatient prescription drug copayment policy in
      the elderly.
AB  - OBJECTIVES: This study uses variance cost analysis and regression analysis as
      tools for investigating the initial effects of Taiwan's outpatient prescription
      drug copayment program in the elderly. Under its new National Health Insurance
      program, Taiwan implemented a prescription drug cost-sharing program August 1,
      1999. We compare an elderly population's prescription drug use after the policy
      was implemented with an elderly population's prescription drug use before the
      policy change to describe initial and general consequences of the drug cost
      sharing program. METHODS: Approximately 240,000 patients aged 65 and over
      representing 1,600,000 outpatient prescriptions were drawn from 21 hospitals in
      the Taipei area for the study using a stratified random sampling method. Variance
      analysis, as used primarily in accounting, was applied to decompose overall cost
      variance of the policy into the sum of variances of several specific factors that
      are important to policymakers. The cost variances of each specific factor can be
      further decomposed into sublevels of analyses. Regression analysis is then
      applied to better understand covariates that might influence drug cost variances
      of significant magnitude. RESULTS: The initial effects of the policy change did
      not reverse the trend of drug cost increases. Instead, there was a significant
      increase in total prescription drug costs in the cost-sharing group
      (approximately 12.86%) and an even higher increase rate in the non-cost-sharing
      group (approximately 51.42%). The main reason for the drug cost increase for the
      cost-sharing group was attributed to an increase in average drug costs per
      prescription (explaining 69.20% of the variance). We found physicians seemed to
      prescribe more expensive drugs and extend prescription duration, especially when
      drug costs exceed the upper bound of the cost-sharing schedule. By contrast, the
      main factor contributing to the increase in drug costs for the non-cost-sharing
      group was an increase in average prescription duration (explaining 64.98% of the
      variance). The increase mainly results from the effect of extended prescriptions
      for chronic diseases that were designed to reduce unnecessary visits for refills.
      DISCUSSION: The significant increase in average drug price per prescription
      indicates that many prescriptions could move above the upper bound of the cost
      sharing schedule. The results suggest that the Bureau of National Health
      Insurance should increase the upper bound. We do not think these effects are
      unique to Taiwan. Rather, these effects should be considered as countries change
      their outpatient drug benefit programs. We also found a decrease in utilization
      of essential drugs with an increase in utilization of nonessential drugs for
      patients subject to copayments. The results suggest potential adverse effects on
      patients' health outcome.

PMID- 14668667
TI  - A randomized trial of four patient satisfaction questionnaires.
AB  - BACKGROUND: Patient satisfaction surveys are increasingly used by hospitals. Many
      questionnaires are available, but little evidence exists to guide the choice of
      the most suitable instrument. OBJECTIVE: To compare the acceptability and patient
      perceptions of 4 patient satisfaction questionnaires. RESEARCH DESIGN: Randomized
      trial of 4 satisfaction questionnaires: Picker, Patient Judgment System (PJS),
      Sequs, and a locally developed Lausanne questionnaire. SUBJECTS: Patients
      discharged from 2 Swiss teaching hospitals (n = 2850). MEASURES: Response rates,
      missing data, completion time, and patient ratings of the questionnaire (5-point
      agree-disagree scale). RESULTS: Response rates were similar across instruments
      (Picker: 70%, PJS: 71%, Sequs: 68%, Lausanne: 73%; P= 0.27). The Picker
      questionnaire had the most missing responses (mean per item: Picker: 3.1%, PJS:
      1.9%, Sequs: 1.6%, Lausanne: 1.1%; P<0.001) and took the longest to complete
      (minutes: Picker: 19.3, PJS: 12.5, Sequs: 13.4, Lausanne: 13.1; P<0.001), but the
      fewest patients indicated that the questionnaire failed to address at least 1
      important aspect of the hospital stay (Picker: 28.2%, PJS: 38.8%, Sequs: 39.1%,
      Lausanne: 28.9%; P<0.001). Patient evaluations of the questionnaires were
      generally similar; the most favorable assessment was chosen by approximately half
      of the respondents (average of 10 items: Picker: 46.5%, PJS: 46.2%, Sequs: 47.4%,
      Lausanne: 48.2%; P= 0.60). Key survey results differed considerably by
      questionnaire. CONCLUSIONS: No questionnaire emerged as uniformly better than the
      others in terms of acceptability and patient evaluations. All 4 could be used for
      patient satisfaction surveys.

PMID- 14668668
TI  - Factors associated with pattern of care before surgery for breast cancer in
      Quebec between 1992 and 1997.
AB  - BACKGROUND: Practice guidelines for breast cancer emphasize the importance of
      establishing an accurate diagnosis using a minimum number of procedures and
      selecting optimal treatment regimens. Understanding the determinants of waiting
      time is essential to develop optimum interventions to reduce delay. OBJECTIVES:
      The purpose of this study is to estimate the extent to which variability in 1)
      the number of procedures before surgery and 2) waiting time from initial
      procedure to surgery are explainable by factors related to the woman, to the
      provider, and to the care setting. RESEARCH DESIGN: Records of physicians' fee
      for-service claims were obtained for 23,370 women undergoing breast cancer
      surgery in Quebec between 1992 and 1997. Multilevel logistic regression was used
      to determine predictors of having multiple procedures before surgery.
      Hierarchical linear regression models were used to identify predictors of waiting
      time, separately for women with lymph node involvement and without this
      involvement. RESULTS: Overall, 23% of the women had 3 or more procedures before
      surgery with significant variation found across hospitals and surgeons. Number of
      procedures was a strong predictor of waiting time. Waiting time also varied by
      stage, age, comorbidity, a history of benign disease, surgical setting, calendar
      time, month of initial procedure, and hospital teaching status. CONCLUSION:
      Although variability in waiting time was more strongly influenced by the
      characteristics of the women rather than by physician- or hospital-related
      factors, most variation remained unexplained by the factors included in this
      study. To reduce overall waiting time, strategies would need to be systemically
      applied.

PMID- 14668669
TI  - Hospitalizations for arthritis and other rheumatic conditions: data from the 1997
      National Hospital Discharge Survey.
AB  - OBJECTIVE: To describe the impact of arthritis and other rheumatic conditions on
      hospitals by describing the magnitude and characteristics of these
      hospitalizations. METHODS: Data from the 1997 National Hospital Discharge Survey
      were used to examine this impact. Arthritis was defined using International
      Classification of Diseases, 9th Revision, Clinical Modification, codes specified
      by the National Arthritis Data Workgroup. Arthritis-related hospitalizations were
      analyzed by principal diagnosis of arthritis and by any-listed arthritis
      diagnosis. RESULTS: In 1997, there were an estimated 744,000 hospitalizations
      with a principal arthritis diagnosis (3% of hospitalizations). Compared with
      nonarthritis hospitalizations, persons hospitalized with a principal arthritis
      diagnosis were older, had fewer comorbidities, had shorter hospital stays, were
      more likely to undergo a procedure, and were more likely to be discharged to
      short- and long-term care facilities. The most common diagnoses and procedures
      related to osteoarthritis. This profile was consistent with a healthier-than
      average hospital population electively admitted for specific procedures and
      subsequent rehabilitation. There were an estimated 2.5 million hospitalizations
      with an any-listed arthritis diagnosis (>9% of hospitalizations). Persons
      hospitalized with an any-listed arthritis diagnosis were older, had more
      comorbidities, and had longer hospital stays than those with principal arthritis
      or nonarthritis hospitalizations. This profile was consistent with a sicker-than
      average hospital population nonelectively admitted for reasons other than their
      arthritis, especially cardiovascular disease. CONCLUSION: Arthritis has a sizable
      impact on the hospital care system. As our population ages, this impact, in both
      human and economic terms, is likely to increase.

PMID- 14668670
TI  - Reliability of clinical guideline development using mail-only versus in-person
      expert panels.
AB  - BACKGROUND: Clinical practice guidelines quickly become outdated. One reason they
      might not be updated as often as needed is the expense of collecting expert
      judgment regarding the evidence. The RAND-UCLA Appropriateness Method is one
      commonly used method for collecting expert opinion. We tested whether a less
      expensive, mail-only process could substitute for the standard in-person process
      normally used. METHODS: We performed a 4-way replication of the appropriateness
      panel process for coronary revascularization and hysterectomy, conducting 3
      panels using the conventional in-person method and 1 panel entirely by mail. All
      indications were classified as inappropriate or not (to evaluate overuse), and
      coronary revascularization indications were classified as necessary or not (to
      evaluate underuse). Kappa statistics were calculated for the comparison in
      ratings from the 2 methods. RESULTS: Agreement beyond chance between the 2 panel
      methods ranged from moderate to substantial. The kappa statistic to detect
      overuse was 0.57 for coronary revascularization and 0.70 for hysterectomy. The
      kappa statistic to detect coronary revascularization underuse was 0.76. There
      were no cases in which coronary revascularization was considered inappropriate by
      1 method, but necessary or appropriate by the other. Three of 636 (0.5%)
      hysterectomy cases were categorized as inappropriate by 1 method but appropriate
      by the other. CONCLUSIONS: The reproducibility of the overuse and underuse
      assessments from the mail-only compared with the conventional in-person conduct
      of expert panels in this application was similar to the underlying
      reproducibility of the process. This suggests a potential role for updating
      guidelines using an expert judgment process conducted entirely through the mail.

PMID- 14668671
TI  - Transitioning the second-generation antihistamines to over-the-counter status: a
      cost-effectiveness analysis.
AB  - BACKGROUND: A U.S. Food and Drug Administration advisory committee deemed the
      second-generation antihistamines (SGA) safe for over-the-counter use against the
      preliminary opposition of the manufacturers. As a result, loratadine is now
      available over-the-counter. First-generation antihistamines (FGA) are associated
      with an increased risk of unintentional injuries, fatalities, and reduced
      productivity. Access to SGA over-the-counter could result in decreased use of
      FGA, thereby reducing deleterious outcomes. The societal impact of transitioning
      this class of medications from prescription to over-the-counter status has
      important policy implications. OBJECTIVE: To examine the cost-effectiveness of
      transitioning SGA to over-the-counter status from a societal perspective.
      RESEARCH DESIGN: A simulation model of the decision to transition SGA to over-the
      counter status was compared with retaining prescription-only status for a
      hypothetical cohort of individuals with allergic rhinitis in the United States.
      Estimates of costs and effectiveness were obtained from the medical literature
      and national surveys. Sensitivity analysis was performed using a second-order
      Monte Carlo simulation. MAIN OUTCOME MEASURES: Discounted, quality-adjusted life
      years saved as a result of amelioration of allergic rhinitis symptoms and
      avoidance of motor vehicle, occupational, public and home injuries and
      fatalities; discounted direct and indirect costs. RESULTS: Availability of SGA
      over-the-counter was associated with annual savings of 4 billion dollars (2.4-5.3
      billion dollars) or 100 dollars (64-137 dollars) per allergic rhinitis sufferer
      and 135,061 time-discounted quality-adjusted life years (84,913-191,802). The
      sensitivity analysis provides evidence in support of these results. CONCLUSION:
      Making SGA available over-the-counter is both cost-saving and more effective for
      society, largely as a result of reduced adverse outcomes associated with FGA
      induced sedation. Further study is needed to determine the differential impact on
      specific vulnerable populations.

PMID- 14668672
TI  - Support for smoking cessation interventions in physician organizations: results
      from a national study.
AB  - OBJECTIVES: To document the extent to which physician organizations, defined as
      medical groups and independent practice associations, are providing support for
      smoking cessation interventions and to identify external incentives and
      organizational characteristics associated with this support. METHODS: This
      research uses data from the National Study of Physician Organizations and the
      Management of Chronic Illness, conducted by the University of California at
      Berkeley, to document the extent to which physician organizations provide support
      for smoking cessation interventions. Of 1587 physician organizations nationally
      with 20 or more physicians, 1104 participated, for a response rate of 70%.
      RESULTS: Overall, 70% of physician organizations offered some support for smoking
      cessation interventions. Specifically, 17% require physicians to provide
      interventions, 15% evaluate interventions, 39% of physician organizations offer
      smoking health promotion programs, 25% provide nicotine replacement therapy
      starter kits, and materials are provided on pharmacotherapy (39%), counseling
      (37%), and self-help (58%). Factors positively associated with organizational
      support include income or public recognition for quality measures, financial
      incentives to promote smoking cessation interventions, requirements to report
      HEDIS (Health Plan Employer Data and Information Set) scores, awareness of the
      1996 Clinical Practice Guideline on Smoking Cessation, being a medical group,
      organizational size, percentage of primary care physicians, and hospital/HMO
      ownership of the organization. CONCLUSION: Physician organizations are providing
      support for smoking cessation interventions, yet the level of support might be
      improved with more extensive use of external incentives. Financial incentives
      targeted specifically at promoting smoking cessation interventions need to be
      explored further. Additionally, emphasis on quality measures should continue,
      including an expansion of HEDIS smoking cessation measures.

PMID- 14668673
TI  - Community-based care and risk of nursing home placement.
AB  - OBJECTIVE: To test the substitution hypothesis, that community-based care reduces
      the probability of institutional placement for at-risk elderly. RESEARCH DESIGN:
      The closure of the Social Health Maintenance Organization (Social HMO) at
      HealthPartners (HP) in Minnesota in 1994 and the continuation of the Social HMO
      at Kaiser Permanente Northwest (KPNW) in Oregon/Washington comprised a "natural
      experiment." Using multinomial logistic regression analyses, we followed cohorts
      of Social HMO enrollees for up to 5 years, 1995 to 1999. To adjust for site
      effects and secular trends, we also followed age- and gender-matched Medicare-Tax
      Equity and Fiscal Responsibility Act (TEFRA) cohorts, enrolled in the same HMOs
      but not in the Social HMOs. SUBJECTS: All enrollees in the Social HMO for at
      least 4 months in 1993 and an age-gender matched sample of Medicare-TEFRA
      enrollees. To be included, individuals had to be alive and have a period out of
      an institution after January 1, 1995 (total n = 18,143). MEASURES: The primary
      data sources were the electronic databases at HP and KPNW. The main outcomes were
      long-term nursing home placement (90+ days) or mortality. Covariates were age,
      gender, a comorbidity index, and geographic site effect. RESULTS: Adjusting for
      variations in the 2 sites, we found no difference in probability of mortality
      between the 2 cohorts, but approximately a 40% increase in long-term
      institutional placement associated with the termination of the Social HMO at
      HealthPartners (odds ratio, 1.43; 95% confidence interval, 1.15-1.79).
      CONCLUSIONS: The Social HMO appears to help at-risk elderly postpone long-term
      nursing home placement.

PMID- 14668674
TI  - Service connection for PTSD is not a gender issue: comment on Murdoch et al.

PMID- 14668677
TI  - Usher in a new era of nurturing.

PMID- 14668678
TI  - What are "Shared Visions--New Pathways"?
AB  - "Shared Visions - New Pathways" (SVNP) is an initiative that will progressively
      sharpen the focus of the accreditation process on operational systems critical to
      patient care safety and quality.

PMID- 14668679
TI  - Prevent discrimination against employees in the reserves.
AB  - Learn how the Uniformed Service Employment and Reemployment Rights Act may affect
      your staff members.

PMID- 14668680
TI  - Breakthroughs beckon new approaches to existing procedures.
AB  - The latest technology supplements cardiac care, sedation monitoring, and
      infection control.

PMID- 14668681
TI  - Evolving infection control standards challenge compliance.
AB  - Advances target JCAHO patient safety goal compliance, hand hygiene and
      antisepsis, intravenous site preparation, and West Nile Virus prevention.

PMID- 14668682
TI  - Telemetry heightens nurses' vigilance, patients' mobility.
AB  - Telemetry monitoring yields better workflow and enhanced productivity.

PMID- 14668683
TI  - Polished automation tools allow patient safety to shine.
AB  - Follow the impact of computerized provider order entry on an acute care team.

PMID- 14668684
TI  - Today's challenges shape tomorrow's technology, part 2.
AB  - In part 2 of this series, examine technologies critical to nursing's viability,
      now and in the near future.

PMID- 14668685
TI  - Implantable pumps deliver innovative pain management.
AB  - Implantable pump technology carries numerous patient care benefits.

PMID- 14668686
TI  - Boost regulatory compliance with electronic nursing documentation.
AB  - Demonstrate accountability and uncompromised patient care with exceptional
      documentation from electronic systems.

PMID- 14668687
TI  - Uncover the latest techniques in wound bed preparation.
AB  - A multistep approach to healing wound beds includes thorough assessment and
      appropriate product selection.

PMID- 14668688
TI  - Hypertrophic obstructive cardiomyopathy: mechanism of obstruction and response to
      therapy.
AB  - Hypertrophic cardiomyopathy is a primary, usually familial, disorder of heart
      muscle whose primary feature is muscular hypertrophy without recognized cause
      that encroaches on the ventricular chamber, reducing chamber area and volume. In
      roughly 25% of cases, there is associated obstruction to left ventricular outflow
      (hypertrophic obstructive cardiomyopathy [HOCM]). This article details the
      mechanism of obstruction in HOCM, focusing on obstruction at the mitral valve
      level, and reviews the pharmacologic and surgical therapies currently available.
      Mainstays of pharmacologic therapy include b-blockers, calcium channel blockers
      (verapamil in particular), and/or disopyramide. Surgical therapies include septal
      myotomy/myectomy, which has become the gold standard to which other therapies are
      compared, and mitral valve replacement. During the past 10 years, atrio
      ventricular sequential pacing and alcohol septal ablation have been proposed as
      less invasive alternatives to surgery. A single, optimal therapy for patients
      with HOCM and refractory symptoms has not been established, and decisions
      regarding surgical versus noninvasive therapies need to be individualized based
      on functional status, comorbidities, local expertise in the surgical and
      nonsurgical techniques, and patient preference.

PMID- 14668690
TI  - Lipid abnormalities in insulin resistant states.
AB  - There are many metabolic consequences of insulin resistance and multiple
      conditions associated with insulin resistant states. The most obvious pathology
      associated with insulin resistance is type 2 diabetes mellitus, but other
      manifestations include hypertension, central obesity, a hypercoagulable state,
      and dyslipidemia. The atherogenic dyslipidemia associated with insulin resistant
      states is characterized by hypertriglyceridemia; an increase in very-low-density
      lipoprotein secretion from the liver; an increase in atherogenic small, dense low
      density lipoprotein; and a decrease in high-density lipoprotein cholesterol. Each
      of these lipid abnormalities is an independent risk factor for coronary artery
      disease, and in concert, the cardiovascular risk is magnified. Therefore, insulin
      resistant states should be identified as early as possible in patients, and these
      lipid abnormalities should be assessed and treated.

PMID- 14668689
TI  - Pharmacologic reperfusion strategies for the treatment of ST-segment elevation
      myocardial infarction.
AB  - The primary goal of therapy for acute ST-segment elevation myocardial infarction
      (STEMI) is rapid, complete, and sustained restoration of infarct-related artery
      (IRA) blood flow. Both pharmacologic and mechanical restoration of antegrade
      coronary blood flow in patients with STEMI have been demonstrated to improve left
      ventricular function, to reduce infarct size, and to reduce mortality. The
      benefits of myocardial reperfusion, including prevention of infarct expansion,
      reduction of ventricular remodeling, and improvement of electrical stability, are
      amplified when IRA patency can be achieved quickly after the onset of symptoms,
      particularly in the first 2 hours-a time window that is particularly challenging
      for mechanical methods of reperfusion, even at high-volume percutaneous coronary
      intervention centers. Despite this demonstrated clinical benefit of reperfusion
      therapy, substantial challenges exist in identifying the precise combination of
      therapeutic agents and strategies that will maximize patient outcomes. This
      review focuses on the evolving pharmacologic treatment strategies for STEMI.

PMID- 14668691
TI  - A modern approach to malignant hilar biliary obstruction.
AB  - Management of patients with malignant hilar biliary obstruction is challenging
      for all specialists involved in their care. Evaluation should focus on potential
      surgical resection, which offers the principal chance of cure; liver
      transplantation is offered as an experimental treatment at a few centers. Attempt
      at curative surgical resection is appropriate for selected tumors and often
      requires partial hepatectomy. Diagnosis and staging is now facilitated by the use
      of magnetic resonance cholangiopancreatography (MRCP), spiral computed
      tomography, and endoscopic ultrasonography, which should largely supplant
      invasive cholangiography. Use of endoscopic retrograde cholangiopancreatography
      and percutaneous transhepatic cholangiography should be limited primarily to
      palliation of jaundice in patients with unresectable tumors and to establish
      tissue diagnoses in ambiguous cases. Palliation of jaundice is optimal with self
      expanding metallic stents. Safe and effective drainage can be achieved by using
      MRCP for targeted endoscopic placement of unilateral metal stents in most cases,
      with bilateral stents rarely required unless undrained ducts are contaminated.
      Other palliative modalities for bile duct tumors include surgical bypass,
      intraluminal and external beam radiation therapy, chemotherapy, and photodynamic
      therapy.

PMID- 14668692
TI  - Postpolypectomy and post-cancer resection surveillance.
AB  - Recent guidelines on postpolypectomy surveillance have focused on identifying
      patients with adenomas who are at high risk for development of significant
      neoplasms (cancer or "advanced adenoma") after clearing colonoscopy and should
      undergo frequent follow-up examinations and those at low risk who require
      infrequent follow-up examinations. This article reviews the guideline
      recommendations from the American College of Gastroenterology, American
      Gastroenterological Association consortium, and the American Cancer Society, and
      discusses the rationale for the recommended intervals of colonoscopic
      examinations in low and high-risk postpolypectomy patients. When colorectal
      cancer is identified, the initial colonoscopic goal in the peri-operative period
      is to clear the colon of synchronous neoplasms. After this is accomplished, the
      goal shifts to performance of colonoscopy at intervals that are appropriate for
      prevention and early detection of second cancers. These intervals often
      approximate those used in postpolypectomy surveillance. An exception to this
      approach is patients with rectal cancer operated by traditional blunt dissection
      techniques, for which there is a rationale for interval flexible sigmoidoscopy
      and/or rectal ultrasound to look for local recurrences.

PMID- 14668693
TI  - The efficacy of oral 5-ASAs in the treatment of active ulcerative colitis: a
      systematic review.
AB  - The authors set out to critically review the current data on the efficacy of oral
      5-aminosalicylic acid (5-ASA) agents for active ulcerative colitis (UC). Thirty
      one studies were identified; 19 met entry criteria. Three trials with mesalamine
      showed statistical significance versus placebo; those with olsalazine or
      balsalazide did not. No agent was statistically different from sulfasalazine. In
      2 of 3 trials of balsalazide versus mesalamine, results for defined primary and
      secondary endpoints failed to demonstrate statistically significant differences.
      Studies suggest that mesalamine is superior to placebo for treating active UC.
      Five-ASA products appear to be as effective as sulfasalazine, but available data
      do not suggest a difference in efficacy between any of the 5-ASA preparations.

PMID- 14668694
TI  - Bioequivalence of azathioprine products.
AB  - All azathioprine oral tablets are considered bioequivalent by the Food and Drug
      Administration based on traditional testing. However, since these tests were
      conducted, it has been determined that some patients have a deficiency of the
      enzyme most responsible for the metabolism of 6-mercaptopurine-thiopurine
      methyltransferase (TPMT). Azathioprine is rapidly converted to 6-mercaptopurine,
      its active metabolite. So it is possible that differences in TPMT activity may
      influence the bioequivalence of azathioprine products among individuals,
      especially those patients deficient in TPMT enzyme activity. However, this
      possibility has not been evaluated.

PMID- 14668695
TI  - Diagnostic and therapeutic utility of B-type natriuretic peptide in patients with
      renal insufficiency and decompensated heart failure.
AB  - Chronic kidney disease (CKD) and congestive heart failure (CHF) are
      epidemiologically and pathophysiologically linked. A recent study in patients
      with severe CHF demonstrated that renal plasma flow was inversely correlated with
      pulmonary capillary wedge pressure, right atrial pressure, pulmonary pressure,
      and right ventricular ejection fraction. This article reviews the utility of B
      type natriuretic peptide (BNP) levels in assessing cardiac function and volume
      status in patients with CKD and examines the safety and efficacy of BNP therapy
      in patients with renal insufficiency and decompensated heart failure.

PMID- 14668696
TI  - Treatment of the acute decompensation of heart failure: efficacy and
      pharmacoeconomics of early initiation of therapy in the emergency department.
AB  - Most patients admitted with acute decompensated heart failure (ADHF) go through
      the emergency department as their initial point of care. New diagnostic tests
      hold the promise to improve the clinical accuracy of the emergency physicians'
      diagnosis. Beyond that there is growing recognition that the treatment provided
      initially has an important impact on the subsequent inpatient course. Basic care
      for ADHF has involved oxygen as needed, diuretics, and, occasionally, topical or
      sublingual nitroglycerin. A substantial proportion of patients are treated with
      vasoactive agents including inotropes and vasodilators such as nitroglycerin and
      nesiritide. Unfortunately, inotropes have not been demonstrated to improve the
      outcome of heart failure and, in fact, may be deleterious. The newer agent,
      nesiritide, has the advantage of being a balanced vasodilator with favorable
      effects on diuresis, symptom relief, and neurohormones. Evidence from registries
      indicates that early initiation of nesiritide compared to delayed initiation
      leads to improved outcomes with shorter lengths of stay, shorter stays in the
      intensive care unit, and a lower mortality rate. This article reviews the initial
      management of ADHF, the role of early initiation of vasodilator therapy, and the
      pharmacoeconomics of nesiritide treatment.

PMID- 14668697
TI  - The Acute Decompensated Heart Failure National Registry (ADHERE): opportunities
      to improve care of patients hospitalized with acute decompensated heart failure.
AB  - Heart failure is a leading cause of hospitalization for adults in the United
      States. Patients hospitalized with acute decompensated heart failure (ADHF) face
      a substantial risk of in-hospital mortality and rehospitalization. Despite the
      large number of patients hospitalized and this substantial risk, data on these
      patients have been limited and there has been little effort to improve the
      quality of care for patients hospitalized with ADHF. The Acute Decompensated
      HEart Failure National REgistry (ADHERE(tm)) was designed to bridge this gap in
      knowledge and care by prospectively studying characteristics, management, and
      outcomes in a broad sample of patients hospitalized with ADHF. Participating
      community and university hospitals identified patients with a primary or
      secondary discharge diagnosis of heart failure and collected medical history,
      management, treatments, and health outcomes via secure web browser technology. As
      of July 2003, 65,180 patients have been enrolled from 263 hospitals. Initial data
      have provided important insights into the clinical characteristics, patterns of
      care, and outcomes of these patients. ADHERE documents significant delays in
      diagnosis and initiation of ADHF therapies as well as substantial under-use of
      evidence-based, guideline-recommended chronic heart failure therapies at hospital
      discharge. As such, there are substantial opportunities to improve the quality of
      care for ADHF patients in the nation's hospitals. The ADHERE Hospital Toolkit has
      been designed to provide hospital teams with effective proactive instruments to
      improve the quality of care for patients with ADHF. If successfully implemented,
      the improvements in short- and long-term clinical outcomes for ADHF patients are
      expected to be substantial.

PMID- 14668698
TI  - Insulin resistance: from benign to type 2 diabetes mellitus.
AB  - Type 2 diabetes has become the most frequently encountered metabolic disorder in
      the world, currently affecting 5% to 10% of most populations, and the incidence
      continues to grow among developing nations. Two fundamental abnormalities are
      involved in the pathogenesis of type 2 diabetes: Resistance to the biologic
      activities of insulin in glucose and lipid metabolism and inadequate insulin
      secretion from the pancreatic B cells. In genetically predisposed individuals,
      type 2 diabetes is pathogenically linked with progressive obesity, especially
      adiposity that is visceral or ectopic in distribution. While microvascular
      complications (retinopathy, nephropathy, neuropathy) continue to plague patients
      with longstanding type 2 diabetes, cardiovascular disease has assumed particular
      importance, accounting for more than 80% of adverse outcomes among patients.
      Since the aggressive management of diabetes and its complications poses a
      considerable challenge, large trials to prevent the progression to overt diabetes
      in persons at high risk have recently demonstrated that lifestyle modification
      and pharmaceutical therapy can be successful approaches. A better understanding
      of the complex relationship between obesity and both the development of type 2
      diabetes and its cardiovascular complications may provide additional treatment
      targets in the future to prevent the devastating chronic morbidity of this
      disorder.

PMID- 14668699
TI  - The relation of insulin resistance syndromes to risk of cardiovascular disease.
AB  - Diabetes mellitus is one of the most common problems challenging physicians in
      the 21st century. Type 2 diabetes mellitus accounts for at least 90% of all
      cases, which can be attributed in part to an aging population and the prevalence
      of obesity and sedentary lifestyles. In addition to the major impact on quality
      of life, diabetes accounts for a significant proportion of global healthcare
      expenditure, with the majority of costs attributable to treatment of its long
      term complications. The principal cause of diabetes mortality is cardiovascular
      disease (CVD). There is a long period, prior to clinical detection of the
      disease, in which insulin resistance and hyperglycemia gradually worsen, and
      vascular complications develop. This article reviews the relationship between
      diabetes and the risk of CVD.

PMID- 14668700
TI  - Treating the diabetic patient: appropriate care for glycemic control and
      cardiovascular disease risk factors.
AB  - Diabetes, a leading cause of morbidity and mortality in the United States, is
      associated with a 2- to 4-fold increase in the risk of coronary artery disease.
      As the population in the United States has aged, the incidence of obesity,
      hypertension, glucose intolerance, and dyslipidemia has increased significantly,
      culminating in the current epidemic of type 2 diabetes mellitus. Strict glycemic
      control must, therefore, be accompanied with proven therapies (such as
      antihypertensives and lipid-lowering agents) to reduce cardiovascular events.
      Patients with type 2 diabetes have average low-density lipoprotein (LDL) levels
      but have an increased number of small, dense LDL particles, which are associated
      with a 3-fold increase in cardiovascular disease. Type 2 diabetes mellitus is
      also associated with increased triglyceride rich atherogenic particles, which
      trigger inflammation. In addition to glycemic control and drug therapy, lifestyle
      modifications (eg, diet, weight loss, and exercise) also play an important role
      in managing diabetes. Therefore, strict glycemic control, pharmacologic therapy,
      and lifestyle modifications are parts of a comprehensive strategy to prevent both
      microvascular and macrovascular events in patients with type 2 diabetes.

PMID- 14668701
TI  - The role of the thiazolidinediones in the practical management of patients with
      type 2 diabetes and cardiovascular risk factors.
AB  - The American Diabetes Association's objective for treating patients with type 2
      diabetes mellitus is to normalize glycemia and glycosylated hemoglobin
      concentrations while controlling blood pressure, cholesterol, and other
      cardiovascular risk factors. This article focuses on the role of
      thiazolidinediones (TZDs) in the management of patients with type 2 diabetes with
      comorbid cardiovascular disease. Insulin resistance is one of the earliest and
      main defects in type 2 diabetes and is strongly linked to comorbid cardiovascular
      conditions. The TZDs rosiglitazone and pioglitazone work mainly by reducing
      insulin resistance and may have the potential to alter the natural history of
      type 2 diabetes and reduce the cardiovascular mortality and morbidity associated
      with this condition.

PMID- 14668702
TI  - The management of the diabetic patient with prior cardiovascular events.
AB  - Patients with diabetes are at high risk for cardiovascular (CV) events and heart
      failure. Approximately 2-3 million diabetics in the U.S. have had a history of
      prior CV events. The prevalence of diabetes in patients with heart failure ranges
      from 24% reported in clinical trials to 47% among hospitalized patients, and an
      estimated 1-2 million persons in the U.S. have diabetes and heart failure.
      Diabetes substantially increases the risk of mortality after acute coronary
      syndromes and also increases the risk of hospitalizations and mortality in
      patients with heart failure. It is now recognized that activation of multiple
      neurohormonal systems is central in the pathophysiology of diabetes, CV events,
      and heart failure. Pharmacologic intervention in these systems (eg, angiotensin
      converting enzyme (ACE) inhibition, aldosterone-receptor antagonism, and beta
      blockade) has been shown to decrease morbidity and mortality in diabetics with
      prior CV events and/or heart failure. Despite this awareness, ACE inhibitors,
      aldosterone antagonists, and beta-blockers are underutilized, and deaths and
      hospitalizations caused by CV events and heart failure in diabetic patients have
      steadily increased. Concerns about an increased incidence of hypoglycemia,
      worsening dyslipidemia, and decreased insulin sensitivity resulting from the use
      of beta-blockers may be preventing physicians from prescribing these agents for
      diabetic patients. Beta-blockade in conjunction with ACE inhibition should be
      standard therapy for all diabetic patients. Optimal glycemic control therapy for
      patients with heart failure has not been well-defined, and there is an urgent
      need for randomized clinical trials to determine optimal treatment.

PMID- 14668703
TI  - Insulin resistance in dilated cardiomyopathy.
AB  - The recognition that insulin resistance is an accompaniment to advanced dilated
      cardiomyopathy is a relatively recent revelation, but the consequences may be
      considerable for the failing heart. The failing heart develops a dependence on
      glucose as its preferred metabolic substrate, given the efficiency of glucose
      oxidation in the generation of high-energy phosphates. The increased preference
      for glucose oxidation requires that glucose transport and oxidation be highly
      regulated. Myocardial insulin resistance in advanced dilated cardiomyopathy
      limits both glucose uptake and oxidation and impairs the heart's ability to
      generate much needed adenosine triphosphate. We provide evidence of insulin
      resistance in dilated cardiomyopathy and explore the relationship to increased
      sympathetic nervous system activation, lipolysis, and the subsequent alteration
      in the insulin signaling cascade. Together, these data provide a growing
      rationale for the development of clinical strategies to overcome insulin
      resistance in dilated cardiomyopathy.

PMID- 14668704
TI  - Epidemiology of contrast-induced nephropathy.
AB  - Decreasing levels of renal function act as a major adverse prognostic factor
      after contrast exposure with or without percutaneous coronary intervention. In
      chronic kidney disease, the most important risk factor for the development of
      contrast-induced nephropathy (CIN) is an estimated glomerular filtration rate </=
      60 mL/min/1.73 m2. Additional risk factors include diabetes, proteinuria, volume
      depletion, heart failure, and intraprocedural events. Overall, CIN occurs in
      approximately 15% of radiocontrast procedures, with < 1% requiring dialysis. CIN
      is directly related to increases in hospitalization length, cost, and long-term
      morbidity. For those patients who require dialysis, a 30% in-hospital mortality
      rate and 80% 2-year mortality rate can be expected. CIN is predictable and
      presents an opportunity to utilize preventive strategies, given the increasing
      numbers of patients undergoing contrast procedures worldwide.

PMID- 14668705
TI  - Understanding the consequences of contrast-induced nephropathy.
AB  - Several investigations have discovered important physiologic links in the
      development of contrast-induced nephropathy (CIN). Studies using a canine kidney
      model showed that contrast media produce a direct cytotoxic effect on the renal
      structures. Also, there is increasing evidence that apoptosis is involved in CIN
      as a result of cell injury. It has been suggested that hemodynamic changes
      resulting from administration of contrast media may contribute to the development
      of CIN, although the data are not conclusive. Several vasoactive substances, such
      as endothelin, prostaglandins, nitric oxide, and adenosine, have been implicated
      in the pathogenesis of CIN, as have immune mechanisms. Several factors contribute
      to the development of CIN, including preexisting renal insufficiency, older age,
      diabetes mellitus, reduced left ventricular systolic function, advanced heart
      failure, acute myocardial infarction, and shock. The authors also present the
      risk score they developed to help clinicians identify patients with different
      responses to contrast exposure.

PMID- 14668706
TI  - What every cardiologist should know about intravascular contrast.
AB  - Contrast-enhanced x-ray imaging remains essential to the diagnosis and treatment
      of many types of cardiac and vascular disease. Despite the rapid advancements in
      less invasive imaging techniques, only traditional angiography provides a high
      resolution, real-time, dynamic view of vascular structures. Cardiologists have
      become concerned about contrast selection since the introduction of new agents
      over the last 2 decades. This concern has sparked three sequential debates within
      our community: the cost effectiveness of low osmolal contrast; whether nonionic
      agents are prothrombogenic; and whether the potential for nephrotoxicity differs
      between contrasts. Following is a summary of clinically relevant aspects of the
      cost effectiveness of low osmolal contrast and the prothrombogenicity of nonionic
      agents. These issues are important not only to those who perform angiography, but
      also to those who refer patients to, or follow them after, the procedure.

PMID- 14668707
TI  - Pathogenesis of contrast-induced nephropathy: experimental and clinical
      observations with an emphasis on the role of osmolality.
AB  - Experimental studies suggest that the pathogenesis of contrast media
      nephrotopathy is due to a combination of renal ischemia and direct tubular
      epithelial cell toxicity. Clinical studies to date have demonstrated a reduction
      in clinical contrast nephropathy with the introduction of low-osmolar and, more
      recently, iso-osmolar contrast media. Numerous experimental studies have examined
      the role of osmolality per se in the pathogenesis of contrast nephropathy, with
      conflicting results. Whether iso-osmolar contrast media are the least nephrotoxic
      iodinated contrast media needs to be determined with large prospective randomized
      clinical trials.

PMID- 14668708
TI  - A review of pharmacologic interventions to prevent contrast-induced nephropathy.
AB  - The serious clinical implications of contrast-induced nephropathy (CIN) have
      focused researchers on prevention strategies. Increased coverage of CIN in major
      medical journals and at major cardiovascular meetings, including the
      Transcatheter Cardiovascular Therapeutics (sponsored by the Cardiovascular
      Research Foundation), American College of Cardiology, and American Heart
      Association conferences, highlight this concern. Development of CIN prevention
      strategies is ongoing, but efforts have been hampered by an incomplete
      understanding of CIN pathophysiology. The most popular theories include contrast
      induced renal tubular ischemia, free radical formation, and a direct tubular
      toxic effect. Proponents of an ischemia model direct clinical trials evaluating
      the efficacy of a variety of vasodilators, while those who favor a free radical
      or direct toxicity theory study antioxidants and free radical scavengers, or a
      variety of contrast agents varying in osmolality, ionicity, and viscosity. A
      comprehensive review of the more important and contemporary CIN prevention trials
      is provided to assist the cardiologist, radiologist, or nephrologist in
      developing his or her own data-driven approach to CIN prevention.

PMID- 14668709
TI  - Recent clinical trials of iodixanol.
AB  - In patients with well-preserved renal function, the choice of contrast agent
      appears to have little impact on the development of contrast-induced nephropathy
      (CIN). However, in patients with underlying renal insufficiency and diabetes
      mellitus, it has been shown that the use of low-osmolar media is associated with
      a lower incidence of CIN compared with high-osmolar agents. Previously, it was
      unknown whether further benefit would be derived from the use of iso-osmolar
      contrast media. Recent studies, including Nephrotoxicity in High-Risk Patients
      Study of Iso-osmolar and Low-Osmolar Nonionic Contrast Media (NEPHRIC), have
      shown a reduction in the incidence of CIN with the iso-osmolar contrast agent
      iodixanol compared with low-osmolar agents in patients with renal insufficiency
      and diabetes. The peak rise in serum creatinine was significantly reduced with
      iodixanol (0.13 mg/dL vs 0.55 mg/dL, P <.001). The incidence of CIN, defined as a
      peak rise > 0.5 mg/dL, was decreased from 26% to 3%, P <.0002 when iodixanol was
      used. An ongoing, multicenter, prospective, double-blind, randomized study
      (Visipaque Angiography/Interventions with Laboratory Outcomes for Renal
      Insufficiency [VALOR]) is evaluating the potential benefit of iodixanol in
      reducing CIN in patients with preexisting renal impairment. Accumulating evidence
      suggests that the use of iso-osmolar contrast agents in conjunction with other
      proven measures, especially adequate intravenous hydration and contrast dosage
      limitation, can reduce the morbidity and mortality associated with CIN. These
      measures have the potential for a significant reduction in health care costs.

PMID- 14668710
TI  - Update: influenza activity--United States, 2003-04 season.
AB  - Influenza began circulating in the United States unusually early this season, and
      influenza activity nationwide is expected to increase. Cases of severe disease,
      including deaths, have been reported in children. This report summarizes
      influenza activity in the United States during the weeks ending October 4
      December 6, 2003. During the week ending December 6, influenza activity was
      reported to CDC as widespread in 24 states. The early season and the unusually
      high and persistent demand for vaccine have resulted in a decreasing supply of
      trivalent inactivated vaccine. Emphasis should be placed on vaccinating persons
      at high risk for complications from influenza, including healthy children aged 6
      23 months. Healthy persons aged 5-49 years who wish to receive vaccine should
      consider being vaccinated with the intranasally administered live, attenuated
      influenza vaccine (LAIV), a substantial supply of which remains available.

PMID- 14668711
TI  - Revised U.S. surveillance case definition for severe acute respiratory syndrome
      (SARS) and update on SARS cases--United States and worldwide, December 2003.
AB  - During the 2003 epidemic of severe acute respiratory syndrome (SARS), CDC and the
      Council of State and Territorial Epidemiologists (CSTE) developed surveillance
      criteria to identify persons with SARS. The surveillance case definition changed
      throughout the epidemic as understanding of the clinical, laboratory, and
      transmission characteristics of SARS-associated coronavirus (SARS-CoV) increased.
      On June 26, CSTE adopted a position statement to add SARS-CoV disease to the
      National Notifiable Disease Surveillance System (NNDSS). The position statement
      included criteria for defining a SARS case for national reporting. On November 3,
      CSTE issued a new interim position statement with a revised SARS case definition.
      This report summarizes the new U.S. surveillance case definition for SARS and
      updates reported cases of SARS worldwide and in the United States.

PMID- 14668712
TI  - Reptile-associated salmonellosis--selected states, 1998-2002.
AB  - During 1998-2002, CDC received reports from state health departments regarding
      Salmonella infections in persons who had contact with reptiles (e.g., lizards,
      snakes, and turtles). Salmonella infections usually cause gastroenteritis but can
      result in invasive illness (e.g., septicemia and meningitis), especially in
      infants and immunocompromised persons. For decades, reptiles have been known as a
      source for salmonellosis; however, numerous reptile owners remain unaware that
      reptile contact places them and other household members, including children, at
      greater risk for salmonellosis. Increasing evidence suggests that amphibians
      (e.g., frogs, toads, newts, and salamanders) also can pose risks for
      salmonellosis in humans. This report describes cases of reptile-associated
      salmonellosis in six states, offers recommendations on preventing transmission of
      Salmonella from reptiles and amphibians to humans, and provides an update on
      state regulations mandating education at pet stores about salmonellosis.

PMID- 14668713
TI  - Public health dispatch: tuberculosis outbreak among homeless persons--King
      County, Washington, 2002-2003.
AB  - The Public Health-Seattle and King County (PH-SKC) Tuberculosis Control Program,
      with assistance from the Washington State Department of Health and CDC, is
      continuing to investigate an ongoing outbreak of tuberculosis (TB) disease among
      homeless persons in Seattle. This report describes patient characteristics,
      methods used to identify active TB cases and contacts at highest risk for
      exposure, and control measures under way to prevent further transmission of this
      outbreak strain of Mycobacterium tuberculosis.

PMID- 14668714
TI  - Presidential Address: Minimally invasive endocrine surgery--standard of treatment
      or hype?

PMID- 14668715
TI  - Results of initial operation for hyperparathyroidism in patients with multiple
      endocrine neoplasia type 1.
AB  - BACKGROUND: Hyperparathyroidism in patients with multiple endocrine neoplasia
      type 1 (MEN1) is characterized by multiglandular disease and a propensity for
      recurrence after parathyroidectomy (PTx). This study analyzes outcomes of a
      cohort of MEN1 patients undergoing initial PTx at one institution. METHODS:
      Between April 1960 and September 2002, 92 patients with MEN1 underwent initial
      PTx. Outcomes were analyzed based on extent of parathyroid resection. RESULTS:
      Fourteen percent had 2.5 or fewer glands resected, 69% had subtotal PTx, and 17%
      had total PTx (88% with immediate autotransplantation). The initial surgical cure
      rate was 98%. Excluding 6 patients lost to follow-up, 33% have developed
      recurrent hyperparathyroidism (in 46% after < or =2.5 PTx, in 33% after subtotal,
      and in 23% after total PTx). Median recurrence-free survival was not
      statistically significantly different between subtotal versus total PTx, but it
      was longer for subtotal and total PTx compared with lesser resection (16.5 vs 7.0
      years, respectively, P=.03). The incidence of severe hypoparathyroidism was 46%
      after total versus 26% after subtotal PTx. CONCLUSIONS: Subtotal and total PTx
      result in durable control of MEN1-associated hyperparathyroidism and have longer
      recurrence-free intervals compared with lesser resection. The high incidence of
      severe hypoparathyroidism after total PTx suggests that subtotal PTx is the
      initial operation of choice in this setting.

PMID- 14668716
TI  - The role of human achaete-scute homolog-1 in medullary thyroid cancer cells.
AB  - BACKGROUND: Human achaete-scute homolog-1 (hASH1) is a transcription factor that
      is expressed highly in neuroendocrine tumors such as medullary thyroid cancer
      (MTC). Thyroid C-cells do not develop in hASH1 knockout mice, which suggests that
      hASH1 is essential for normal C-cell development. METHODS: To determine the
      effect of raf-1 induction on hASH1 and hormone production, we used an estrogen
      inducible raf-1 construct in MTC cell line (TT) cells (TT-raf cells). TT or TT
      raf cells were treated with control or 1 microM estradiol. After 48 hours, the
      cells were analyzed for levels of hASH1 and chromogranin A by Western blotting
      and for calcitonin production by enzyme-linked immunosorbent assay. RESULTS:
      Activation of raf-1 in the TT-raf cells resulted in high levels of phosphorylated
      MEK and ERK1/2, a morphologic transdifferentiation, and a decrease in
      chromogranin A and calcitonin levels that are associated with a reduction in
      hASH1 production. Furthermore, using MEK inhibitors, we demonstrated that these
      raf-1-mediated changes are dependent on MEK but not ERK1/2 activation.
      CONCLUSION: hASH1 down-regulation by raf-1 in MTC cells is associated with a
      significant decrease in hormone production. Thus, hASH1 appears to be important
      in the endocrine phenotype of MTC tumors and may serve as a molecular target for
      the treatment of patients with MTC.

PMID- 14668717
TI  - Androgen-secreting adrenal tumors.
AB  - BACKGROUND: Adrenal tumors that secrete androgens exclusively are extraordinarily
      rare. The aim of this study was to characterize patients with pure androgen
      secreting adrenal tumors. METHODS: A retrospective chart review from January 1946
      through November 2002 identified 11 female patients with pure androgen-secreting
      adrenal tumors. RESULTS: The mean age was 23.4 years (range, 1-52). The most
      common presenting symptoms were hirsutism, acne, and clitoral enlargement.
      Elevated 17-ketosteroids were found in seven of nine tested patients. Computed
      tomogram, ultrasound, or both localized tumors in six of seven patients. All
      tumors were surgically resected, one laparoscopically, all without complications.
      Five of the 11 tumors were malignant. Mean weight and mean maximal diameter for
      benign and malignant tumors were 44 g and 4.2 cm and 232 g and 9.8 cm,
      respectively. Mean hospital stay was 8.5 days, with excess androgen production
      resolved in all patients. Recurrence and disease-related death occurred in only
      one patient who had pulmonary metastases at diagnosis. The remaining patients had
      no recurrence of tumor at mean follow-up of 11.7 years (range, 0.5-32 years).
      CONCLUSIONS: Pure androgen-producing tumors are extremely rare. Approximately 50%
      are benign, and surgical resection provides excellent treatment if the tumors are
      not metastatic at the time of diagnosis.

PMID- 14668720
TI  - Medullary thyroid carcinoma: results of a standardized surgical approach in a
      contemporary series of 80 consecutive patients.
AB  - BACKGROUND: The surgical management and follow-up strategy in patients with
      medullary thyroid carcinoma (MTC) remain controversial because of the lack of
      data on the natural history of these tumors and their patterns of progression.
      METHODS: We reviewed the records of all patients who underwent a cervical
      operation for MTC between 1991 and 2002. Compartment-oriented surgery (COS) was
      performed to minimize the risk of cervical recurrence. RESULTS: We identified 92
      consecutive patients who underwent a cervical operation for MTC: 80 had invasive
      MTC, and 12 had C-cell hyperplasia after prophylactic thyroidectomy for familial
      MTC. Ten (13%) of the 80 patients with invasive MTC presented with distant
      metastases and underwent COS to achieve local-regional control; cervical
      recurrence developed in none, but three have died of MTC. The remaining 70
      patients underwent COS for primary (n=23) or recurrent (n=47) MTC. Disease
      recurred in 18 (26%) of these 70 patients at a median follow-up of 35 months,
      with 10 (14%) of the recurrences being cervical. Recurrent disease was associated
      with a basal calcitonin level of >250 pg/mL in all but four patients, two of whom
      showed tumor dedifferentiation. In contrast, only 5 (11%) patients without
      evidence of recurrence had basal calcitonin levels of >250 pg/mL at last follow
      up. CONCLUSIONS: Complete COS minimizes cervical recurrence. Radiographic
      evidence of recurrent disease is unlikely when the calcitonin level is < or =250
      pg/mL. These data could be used to develop a logical, cost-effective treatment
      and follow-up strategy for patients with MTC.

PMID- 14668719
TI  - RET rearrangements in archival oxyphilic thyroid tumors: new insights in
      tumorigenesis and classification of Hurthle cell carcinomas?
AB  - BACKGROUND: Oncocytic carcinomas (Hurthle cell carcinomas [HCCs]) are commonly
      considered a subgroup of follicular thyroid carcinomas (FTCs). Recent
      characterization of a subgroup of "Hurthle cell" papillary thyroid carcinomas
      (PTCs) was based on the identification of PTC-specific RET hybrid oncogenes in
      HCCs. METHODS: We examined 27 HCCs, 4 oxyphilic FTCs, 5 oxyphilic PTCs, 2 poorly
      differentiated carcinomas arising from HCCs (HCC-UTCs), and 16 oxyphilic
      adenomas. Total RNA was extracted from paraffin-embedded thyroid neoplasms by a
      novel macrodissection technique that uses a cylindric punch. After reverse
      transcription-polymerase chain reaction-based screening for RET rearrangements,
      the samples were tested for all known RET/PTC 1 to 11 hybrids with the use of
      artificially constructed chimeric sequences as controls. RESULTS: The elimination
      of C cells by punching dissection significantly reduced RET wild-type expression.
      RET hybrid oncogenes (7x RET/PTC1, 1x RET/PTC1L, 2x RET/PTC3, 5 uncharacterized
      RET/PTCx) were demonstrated in 7 of 27 HCCs, in 0 of 4 oxyphilic FTCs, in 4 of 5
      oxyphilic PTCs, in 1 of 2 HCC-UTCs, and in 3 of 16 oxyphilic adenomas.
      CONCLUSION: Our results suggest that the expression of rearranged RET hybrid
      oncogenes (1) is present in a similar percentage of HCCs when compared with the
      literature on nonoxyphilic PTCs, (2) defines PTC-like HCCs better than
      histomorphologic characterization, (3) excludes HCCs as a subgroup of FTCs, and
      (4) may play a role in the early tumorigenesis of oncocytic tumors.

PMID- 14668721
TI  - Prognostic value of hMLH1 methylation and microsatellite instability in
      pancreatic endocrine neoplasms.
AB  - BACKGROUND: The aberrant promoter methylation of the mismatch repair gene, hMLH1,
      is associated with microsatellite instability (MSI) in cancer cells and often is
      associated with a favorable prognosis. METHODS: Pancreatic endocrine neoplasms
      (PENs) were obtained from 48 patients who underwent surgical resection.
      Methylation-specific polymerase chain reaction was used to detect methylation in
      the hMLH1 promoter. Tumor MSI at loci BAT26, BAT25, D2S123, D5S346, and D17S250
      was determined with microsatellite polymerase chain reaction. RESULTS:
      Hypermethylation of the hMLH1 promoter was present in 11 of 48 PENs (23%). Five
      of the 11 hMLH1-methylated PENs were found to be microsatellite unstable, and MSI
      was restricted to PENs with hMLH1 hypermethylation. Tumor recurrence at 2 years
      after surgical resection was significantly less common among the hMLH1-methylated
      PENs (11%), compared with the unmethylated PENs (35%; P=.038). Patients with
      hMLH1-methylated PENs experienced improved 5-year survival (100%) compared with
      patients with unmethylated tumors (56%; P=.010). Likewise, MSI-positive PENs were
      associated with improved survival compared with MSI-negative tumors (100% vs 59%;
      P=.017) at 5 years. CONCLUSION: As in hereditary nonpolyposis colorectal cancer
      in which MSI is associated with improved survival, methylation of hMLH1 leads to
      MSI in PENs and affords a favorable prognosis.

PMID- 14668722
TI  - The impact of minimally invasive parathyroidectomy on the way endocrinologists
      treat primary hyperparathyroidism.
AB  - BACKGROUND: Minimally-invasive parathyroidectomy (MIP) appears to be changing
      preoperative treatment and referral patterns for sporadic, nonfamilial, non
      multiple endocrine neoplasia, primary hyperparathyroidism (PHPT). METHODS: The
      American Association of Clinical Endocrinologists membership was surveyed by mail
      (n=1406 members) regarding physician practices and surgical referral patterns for
      PHPT. RESULTS: Seven hundred eighty-eight respondents (56%) practiced 17.0+/-0.4
      years and referred 63%+/-1% of patients with PHPT for operation. Most
      endocrinologists (90%) used localizing studies before surgical referral
      (sestamibi, ultrasound scanning, technetium/thallium scanning, magnetic resonance
      imaging, computed tomography). Respondents identified symptoms, calcium
      homeostasis, bone density, health status, age, and general anesthesia risk as the
      most important considerations for surgical referral. Most respondents (79%)
      indicated that MIP availability would increase the number of patients who were
      referred for operation (P<.001), although most of the respondents stated that MIP
      would change the extent and duration of preoperative evaluations (P<.001).
      Respondents in practice for fewer years were more likely to refer patients for
      MIP (P<.001) and minimize preoperative evaluation (P<.05). Endocrinologists who
      had a patient with a complication after traditional parathyroidectomy were more
      likely to embrace MIP (P<.05). CONCLUSIONS: MIP availability decreases the extent
      and duration of preoperative evaluation while decreasing the time from diagnosis
      to referral. MIP also lowers the endocrinologists' surgical referral threshold
      for PHPT, although it emphasizes the perceived shortcomings of traditional
      parathyroidectomy that are held by many physicians.

PMID- 14668723
TI  - Is preoperative iodine 123 meta-iodobenzylguanidine scintigraphy routinely
      necessary before initial adrenalectomy for pheochromocytoma?
AB  - BACKGROUND: Iodine 123 meta-iodobenzylguanidine (MIBG) scintigraphy has been used
      in patients with clinical suspicion of pheochromocytoma to confirm the nature of
      an adrenal or extraadrenal mass or to identify occult disease. Additionally, it
      may be used to identify unsuspected bilaterality or metastases in the setting of
      a known unilateral adrenal mass before operation. We sought to determine the role
      of (123)I MIBG scintigraphy in this apparently routine preoperative setting. Our
      hypothesis was that (123)I MIBG would provide additional preoperative information
      that could modify operative intervention. METHODS: All patients undergoing (123)I
      MIBG scintigraphy at our institution between 1992 and 2002 were identified. MIBG
      results, operative procedures and findings, and pathologic findings were
      retrospectively reviewed and compared. RESULTS: The (123)I MIBG scintigraphy was
      performed in a total of 315 patients. Of these, 48 were patients with an initial
      biochemical diagnosis of pheochromocytoma and a unilateral adrenal mass. 47 of
      the 48 (98%) primary scans were positive for a single focus of activity
      concordant with anatomic imaging data from computed tomography or magnetic
      resonance imaging and operative findings. The (123)I MIBG did not reveal
      unsuspected metastatic or bilateral disease in any patient. CONCLUSION: In this
      large series of patients undergoing (123)I MIBG scintigraphy, the test served
      only to confirm diagnostic impressions and corroborate anatomic imaging. The
      (123)I MIBG did not alter the operative management of any patient with a solitary
      adrenal lesion in the clinical context of biochemically-proven catecholamine
      excess.

PMID- 14668724
TI  - Who performs endocrine operations in the United States?
AB  - BACKGROUND: Endocrine surgery is a discipline that is dedicated to high-quality
      care of patients with endocrine surgical disease. The relationship between its
      "identity" as a separate field and clinical practice patterns is not known.
      METHODS: The National Inpatient Sample was searched by the International
      Classification of Diseases-9th revision-Clinical Modification codes for
      parathyroidectomy, thyroidectomy, and adrenalectomy for the years 1988 through
      2000. The surgeons who performed these operations were profiled by 2 methods:
      Method A, by the percentage of the total primary International Classification of
      Diseases-9th revision-Clinical Modification procedure codes that were the
      selected endocrine procedures; method B, by absolute number of index endocrine
      procedures performed per year. Only patients with complete coding data for the
      surgeons were included. RESULTS: In this sample, surgeons whose practice was
      comprised of 25% or less of these endocrine procedures performed 11,071
      parathyroidectomies (78% of total), 46,210 thyroidectomies (82% of total), and
      4209 adrenalectomies (94% of total). In contrast, surgeons whose practice was
      comprised of more than 75% of these endocrine procedures performed 769
      parathyroidectomies (5% of total), 1560 thyroidectomies (3% of total), and 128
      adrenalectomies (3% of total). CONCLUSION: If these data can be extrapolated to
      indicate generalized practice patterns, the majority of common operations for
      endocrine disease are performed by surgeons whose practice is not focused on
      endocrine surgery. However, much of this effect is due to the fact that non
      endocrine surgeons far outnumber endocrine surgeons. This understanding of
      clinical practice patterns will be important to consider during future studies
      that seek to determine the relationship between surgeon volume and patient
      outcomes.

PMID- 14668725
TI  - Intragenic allelic loss and promoter hypermethylation of the RIZ1 tumor
      suppressor gene in parathyroid tumors and pheochromocytomas.
AB  - BACKGROUND: Loss of heterozygosity (LOH) at chromosome 1p is a common abnormality
      in both parathyroid tumors and pheochromocytomas. The recently characterized
      tumor suppressor gene RIZ1, located at 1p36, has emerged as a putative candidate
      to be involved in endocrine tumorigenesis. MATERIAL: Presence of allelic loss,
      promoter hypermethylation, and mutational aberrations of the RIZ1 gene were
      investigated using PCR-based techniques in 47 parathyroid tumors and 23
      pheochromocytomas. Gene expression studies used the RNAse protection assay.
      RESULTS: RIZ1 mRNA is expressed in pathologic tissues of the parathyroid and
      adrenal medulla. Thirteen of 47 (28%) parathyroid tumors, and 9/23 (39%)
      pheochromocytomas displayed LOH within the RIZ1 gene locus. Promoter
      hypermethylation of RIZ1 was detected in 36% of the parathyroid tumors and was
      related to LOH at the RIZ1 locus (P=.01), and absence of somatic mutation of the
      MEN1 gene (P=.044). In the pheochromocytomas, none of the benign tumors, but 2/4
      malignant specimens exhibited RIZ1 promoter hypermethylation. CONCLUSION:
      Alteration of the RIZ1 gene locus via intragenic allelic loss and promoter
      hypermethylation seem common in parathyroid tumors. Inactivation of the RIZ1 gene
      may cause parathyroid tumorigenesis via a mechanism in which genetic alteration
      of the MEN1 gene is redundant.

PMID- 14668726
TI  - Therapy for calciphylaxis: an outcome analysis.
AB  - BACKGROUND: Violaceous skin lesions that progress to nonhealing ulcerations and
      gangrene characterize calciphylaxis. These lesions, which are associated with
      secondary hyperparathyroidism, are resistant to medical therapy and may lead to
      amputation, uncontrollable sepsis, and death. METHODS: In this retrospective
      analysis, patient, disease, and treatment variables were obtained from the
      patients' medical records. Paired t-tests, chi-square analysis, and two-tailed
      Fisher's exact tests compared variables. Survival curves were generated using the
      Kaplan-Meier method; the log-rank test determined survival differences. RESULTS:
      From 1993 to 2001, 35 patients were treated; 26 (74%) were female and 20 (57%)
      were African-American. The cause of the renal failure was hypertension in 37% and
      diabetes mellitus in 26%. Twenty-three patients (66%) underwent a parathyroid
      resection involving 4 glands and autotransplantation in 12, 3(1/2) glands in 7,
      and <3(1/2) glands in 4. Median follow-up was 26 months (range 2 to 90 months).
      Surgical patients showed improvement in serum calcium, phosphate, and parathyroid
      hormone values (P<.05) and had a longer median overall survival (80 months) than
      nonsurgical patients (35 months) (P<.001). CONCLUSIONS: Parathyroid resection for
      calciphylaxis reduces serum calcium, phosphate, and parathyroid hormone values
      and improves clinical response and overall survival.

PMID- 14668727
TI  - Role of preoperative ultrasonography in the surgical management of patients with
      thyroid cancer.
AB  - BACKGROUND: Cervical recurrence occurs in up to 30% of patients with
      differentiated thyroid carcinoma. We retrospectively compared preoperative
      transcutaneous ultrasonography and physical examination (PE) results in the
      detection of local-regional metastases (lymph node and soft tissue) in patients
      with thyroid cancer. METHODS: Data were collected retrospectively from the
      medical records of patients with thyroid carcinoma who underwent preoperative
      ultrasonography. Patients were divided into 3 groups: group 1, those undergoing
      primary thyroid/neck surgery; group 2, those undergoing reoperation for
      persistent disease; and group 3, those undergoing reoperation for recurrent
      thyroid carcinoma. For each group, we recorded the frequencies with which
      ultrasonography detected disease in a neck compartment (central or lateral) that
      was normal on PE. RESULTS: Two hundred twelve patients underwent operation for
      primary, persistent, or recurrent papillary (n=130), medullary (n=61), or
      follicular/Hurthle cell (n=21) carcinoma. Ultrasonography detected additional
      sites of metastatic disease not appreciated on PE in 21 (20%) of 107 group 1
      patients, 9 (32%) of 28 group 2 patients, and 52 (68%) of 77 group 3 patients.
      The surgical procedure performed was altered by the information obtained from
      preoperative ultrasonography in 82 (39%) of the 212 patients. Of the 107 group 1
      patients, cervical recurrence has been detected in only 6 (6%) at a median follow
      up of 36 months, in spite of 67 (63%) having tumors larger than 2 cm or lymph
      node metastases. CONCLUSIONS: Preoperative high-quality ultrasonography detected
      lymph node or soft-tissue metastases in neck compartments believed to be
      uninvolved by PE in 39% of patients. Ultrasound findings altered the operative
      procedure in these patients, facilitating complete resection of disease and
      potentially minimizing local-regional recurrence.

PMID- 14668728
TI  - Iodine -131 metaiodobenzylguanidine is an effective treatment for malignant
      pheochromocytoma and paraganglioma.
AB  - INTRODUCTION: Iodine 131-meta-iodobenzylguanidine ((131)I-MIBG) has been applied
      to the palliative treatment of metastatic pheochromocytoma in small studies. We
      report our institutional experience for the treatment of metastatic
      pheochromocytoma and paraganglioma. METHODS: We performed a retrospective review
      of 33 patients with metastatic pheochromocytoma (n=22) and paraganglioma (n=11)
      treated at our institution with (131)I-MIBG over a 10-year period. RESULTS:
      Patients received a mean dose of 388+/-131 mCi (131)I-MIBG. Median survival after
      treatment was 4.7 years. Most patients experienced a symptomatic response leading
      to an improved survival (4.7 years vs 1.8 years, P<.01). Patients with a
      measurable hormone response demonstrated an increased survival in comparison to
      those with no response (4.7 years vs 2.6 years, P=.01). Patients who received a
      high dose (>500 mCi) as their initial therapy also had improved survival (3.8
      years vs 2.8 years, P=.02). CONCLUSION: These data support (131)I-MIBG treatment
      for select patients with metastatic pheochromocytoma. In our experience,
      prolonged survival was best predicted by symptomatic and hormone response to
      (131)I-MIBG treatment. An initial dose of 500 mCi may be optimal. The benefit of
      (131)I-MIBG treatment for metastatic pheochromocytoma must also be weighed
      against its side effects.

PMID- 14668729
TI  - Detection and prognostic relevance of cytokeratin 20 in differentiated and
      anaplastic thyroid carcinomas by RT-PCR.
AB  - BACKGROUND: Metastatic disease in epithelial cancer results from tumor cell
      dissemination. We investigated an expression of cytokeratin 20 (CK20) by reverse
      transcriptase-polymerase chain reaction (RT-PCR) in differentiated (DTC) and
      anaplastic thyroid carcinomas (ATC) and correlated the results with TNM
      categories and the clinical follow-up. METHODS: Tissue and blood samples of 32
      patients with papillary (PTC), 17 patients with follicular (FTC), and 7 patients
      with ATC were obtained during operation and subjected to CK20 RT-PCR. RESULTS: An
      expression of CK20 transcripts was detected in 47% of the tissue samples of PTC,
      71% of the FTC, and 14% of the ATC. Patients with CK20-positive FTC had a
      significantly better outcome than patients with CK20-negative FTCs (P=.0016).
      Disseminated tumor cells were found in 9 of 22 (41%) blood samples of patients
      with CK20-positive carcinomas. The detection of CK20 transcripts in peripheral
      blood correlated with tumor categories. Four of 8 (50%) patients with DTC and
      circulating tumor cells developed local or distant recurrence compared with 3 of
      13 (23%) patients with CK20-positive carcinomas and CK20-negative blood samples.
      CONCLUSION: Our results suggest that CK20 might be a suitable differentiation
      marker in thyroid carcinomas. In patients with CK20-positive tumors, those with
      CK20-positive blood samples had a poorer prognosis. We suggest that patients with
      thyroid cancer with positive CK20 blood samples should be evaluated for further
      adjuvant therapies after surgery.

PMID- 14668730
TI  - Comparison of intraoperative iPTH assay (QPTH) criteria in guiding
      parathyroidectomy: which criterion is the most accurate?
AB  - BACKGROUND: The quick parathyroid hormone assay (QPTH) reliably measures intact
      parathyroid hormone (iPTH) levels intraoperatively. The accuracy in predicting
      postoperative calcemia is related to blood sample timing and the criteria
      applied. To improve specificity or to decrease the cost of QPTH, several criteria
      have been used to predict complete excision. This study compares the Miami
      criterion with other published QPTH criteria in predicting operative outcome.
      METHODS: QPTH and the Miami criterion (iPTH drop > or =50% from the highest of
      either preincision or pre-excision level at 10 minutes after gland excision),
      were used to predict postoperative calcium levels of 341 consecutive patients
      with sporadic primary hyperparathyroidism who were followed > or =6 months after
      the operation or recognized as operative failures. Intraoperative iPTH values of
      these patients were reanalyzed with the use of 5 published criteria to predict
      complete resection. Postoperative calcium levels were correlated with criteria
      predictions. RESULTS: Miami criterion correctly predicted postoperative calcium
      levels in 329 of 341 patients and was incorrect in 12 (3 false positives, 9 false
      negatives). With the use of other criteria, 2 of the 3 false-positive results
      would be prevented, but the 3% rate of false-negative predictions would increase
      to between 6% and 24%, causing unnecessary neck explorations to search for
      multiglandular disease. CONCLUSIONS: Surgeons trying to increase QPTH specificity
      significantly decrease the accuracy and intraoperative usefulness of the assay.
      The Miami criterion has the highest accuracy when compared with other criteria.

PMID- 14668731
TI  - Peak stimulated insulin secretion is associated with specific changes in gene
      expression profiles in sporadic insulinomas.
AB  - BACKGROUND: The molecular pathways that are responsible for pathologic insulin
      secretion by insulinomas have not been characterized. We studied gene expression
      profiles from insulinomas and determined associations between these changes and
      preoperative peak serum insulin levels. METHODS: Ten patients with insulinomas
      underwent calcium-stimulated arteriography and surgical resection. Tumor RNA was
      isolated; corresponding complementary DNA was hybridized to 10K human
      complementary DNA arrays. Pooled human islet cell complementary DNA served as the
      control. Cluster analysis of gene expression and analysis of expression ratios
      was performed. RESULTS: Nineteen genes were up-regulated at least 3-fold in
      insulinomas compared with controls, which included the genes for islet amyloid
      polypeptide and proprotein convertase type 2. Cluster analysis revealed 2 groups
      of patients with insulinoma and with distinct patterns of gene expression. Mean
      peak serum insulin values between groups were 196 and 1100 (U/mL (P<.05), which
      demonstrates a significant difference in insulin response to calcium stimulation
      between these 2 groups. CONCLUSION: We show that genes that are relevant to the
      pathogenesis of hyperinsulinemia are expressed preferentially in insulinomas. In
      addition, patients with a distinct and common pattern of gene expression had
      significantly higher stimulated insulin secretion levels. The study of these
      genes may help to identify the biochemical pathways that are responsible for
      pathologic insulin secretion.

PMID- 14668732
TI  - Intracaval endovascular ultrasonography for large adrenal and retroperitoneal
      tumors.
AB  - BACKGROUND: An accurate diagnosis of inferior vena cava (IVC) invasion is
      important in deciding the surgical strategy for a large adrenal tumor. We
      investigated the diagnostic value of intracaval endovascular ultrasonography
      (ICEUS) for invasion of the IVC by a large adrenal tumor. METHODS: Nine of 163
      patients with adrenal and retroperitoneal tumors underwent ICEUS between 1993 and
      2002. Intravascular ultrasonography was performed through the right femoral vein
      with the use of an 8Fr, 20-MHz transducer. The diagnostic criterion for detecting
      IVC invasion with ICEUS was identification of destruction of a single echogenic
      layer of the IVC wall or identification of an intracaval tumor mass. The ICEUS
      finding was confirmed by pathologic examination. RESULTS: The mean diameter of
      the tumors in 9 patients undergoing ICEUS and resection was 12.6 cm (range, 8.6
      16 cm). Pathologic diagnosis varied: adrenocortical carcinoma, 4; malignant
      pheochromocytoma, 1; leiomyosarcoma, 1; metastatic lung cancer, 1; paraganglioma,
      1; and neurilemmoma, 1. Vascular invasion was identified in 2 patients by ICEUS
      and confirmed by examination of resected specimens. The sensitivity, specificity,
      and positive predictive values of ICEUS for the diagnosis of the IVC invasion
      were 100%, 100%, and 100%, respectively. However, these values for computed
      tomography were 100%, 14%, and 25%, respectively; and for cavography, 100%, 57%,
      and 40%, respectively. CONCLUSIONS: ICEUS provides confirmatory information
      regarding tumor invasion of the IVC. This modality also can assist in formulating
      an operative strategy for large adrenal or retroperitoneal tumors.

PMID- 14668733
TI  - Double adenomas revisited: nonuniform distribution favors enlarged superior
      parathyroids (fourth pouch disease).
AB  - BACKGROUND: A double adenoma (DA) is a recognized clinical entity of primary
      hyperparathyroidism (HPT) and is presumed to have uniform location distribution.
      We reviewed our experience with 2-gland parathyroid disease to identify anatomic
      patterns and implications for surgical management. METHODS: Clinical
      characteristics were reviewed for 828 consecutive patients with HPT at 2
      endocrine referral centers that practice bilateral neck exploration with
      intraoperative parathyroid hormone (IOPTH) measurement. RESULTS: Fifteen percent
      (127 of 828) of HPT patients demonstrated 2 enlarged glands; 13% (107 of 828), 3-
      or 4-gland hyperplasia; and 71% (592 of 828), single adenomas. DAs in superior
      parathyroids affected 57 of 127 (45%) patients, an observed frequency 3-fold
      higher than expected (P<.001, chi-square test). DAs were larger than normal
      glands (240+/-575 mg vs 28+/-23 mg, P<.001), and superior parathyroid adenomas
      were larger than adenomas at other sites (421+/-983 mg vs 202+/-353 mg, P=.002).
      Technetium 99 metastable (Tc99m)-sestamibi imaging and IOPTH identified DAs
      correctly in only 5 of 84 (6%) and 19 of 75 (25%) of patients tested,
      respectively. CONCLUSIONS: DAs have nonuniform anatomic distribution with
      predilection for abnormal growth in bilateral superior parathyroids-embryologic
      remnants of the fourth branchial pouch. Since additional abnormal glands were
      detected by observation with technetium 99 metastable (Tc99m)-sestamibi imaging
      and IOPTH rarely aiding detection, unilateral neck exploration may predispose to
      persistent or recurrent HPT.

PMID- 14668734
TI  - The diagnostic dilemma of follicular variant of papillary thyroid carcinoma.
AB  - BACKGROUND: Given the difference in surgical management between follicular
      neoplasms and papillary thyroid carcinoma (PTC), we sought to determine the
      sensitivity of fine-needle aspiration (FNA) and intraoperative pathologic study
      (IP), frozen section and cytologic study, in establishing a diagnosis of
      follicular variant of papillary thyroid carcinoma (FVPTC) and how these
      techniques impact operative management. METHODS: A retrospective chart review was
      performed of patients who underwent thyroidectomy for nodular disease between
      June 1997 and June 2002 identifying patients with a final diagnosis of FVPTC. FNA
      and IP results were reviewed in this group of patients and correlated with those
      of final histopathologic study. The sensitivity of FNA and IP was calculated.
      RESULTS: Eighty-two patients had a final diagnosis of FVPTC. Eighty-six
      preoperative FNAs were obtained in 80 patients, leading to a diagnosis of PTC in
      7 (sensitivity 9%). Intraoperative pathologic study was performed in 31 patients
      with suspicious FNA results, of which 13 were definitive for PTC (sensitivity
      42%). Overall, IP was obtained in 42 patients, of which 15 were positive for PTC
      (sensitivity 36%). CONCLUSION: Although the sensitivity of FNA in establishing a
      diagnosis of FVPTC is low, FNA identifies patients with suspicious lesions in
      whom IP is important in guiding operative management.

PMID- 14668735
TI  - Circadian cardiac autonomic nerve dysfunction in primary hyperparathyroidism
      improves after parathyroidectomy.
AB  - BACKGROUND: Primary hyperparathyroidism has been associated with premature death
      in cardiovascular diseases, but reversibility and background mechanisms are
      uncertain. This study investigates autonomic nervous function in
      hyperparathyroidism because disturbances in this respect have been related to
      increased cardiovascular morbidity. METHODS: Twenty-one consecutive patients with
      hyperparathyroidism and 23 matched control subjects without interfering
      medication underwent electrocardiographic recordings and ambulatory blood
      pressure (ABP) determination during a 24-hour period. Patients were re-examined
      at normocalcemia 1 year after parathyroidectomy. Heart rate variability was
      analyzed in subjects with sinus rhythm and normal atrioventricular conduction;
      time domain measures were calculated from the RR-intervals, and frequency domain
      variables were obtained with an autoregressive algorithm, which expressed power
      distribution (high, low, or very low frequency). RESULTS: Nocturnal increase in
      low frequency was blunted in cases versus control subjects (103+/-128 m(2) vs
      430+/-171 m(2); P=.03). Very low frequency at nighttime correlated inversely with
      serum parathormone (r=-0.33; P<.05) and increased postoperatively (P=.03). ABP
      was higher both at daytime and nighttime (P<.05) in patients and remained
      unchanged after surgery. Systolic ABP correlated with the parathormone (r=0.47;
      P<.01). CONCLUSION: Results suggest altered circadian autonomic function in
      hyperparathyroidism that can improve after parathyroidectomy. Despite elevated
      blood pressure, ABP shows retained diurnal rhythm, which indicates different
      pathophysiologic mechanisms behind the 2 predictors of cardiovascular death in
      hyperparathyroidism.

PMID- 14668736
TI  - Critical size of residual adrenal tissue and recovery from impaired early
      postoperative adrenocortical function after subtotal bilateral adrenalectomy.
AB  - BACKGROUND: Subtotal bilateral adrenalectomy may preserve adrenocortical
      function. Little is known about the early postoperative function of the adrenal
      remnant. METHOD: In 10 patients with bilateral adrenal tumors (pheochromocytomas,
      adrenocortical nodular hyperplasia, and adrenal metastases), plasma
      adrenocorticotropic hormone (ACTH), serum cortisol, and maximal cortisol
      liberation were examined with an ACTH test after subtotal bilateral
      adrenalectomy, which left 15% to 30% of adrenal tissue in situ. RESULTS: In the
      early postoperative period, all patients had normal basal serum cortisol levels
      (mean, 415+/-208 nmol/L; normal morning range, 138-690 nmol/L) but pathologically
      increased plasma ACTH levels (mean, 55+/-42 pmol/mL; normal, <10.1 pmol/L). In 6
      patients, a pathologic ACTH test result was observed. During follow-up (mean,
      11.3+/-7.6 months), all patients were found to have a normal ACTH test result.
      None of the patients required steroid supplementation. However, in patients with
      both familial pheochromocytoma and impaired adrenocortical function during the
      early postoperative period, the maximal increase of serum cortisol after ACTH
      stimulation was significantly reduced (mean, 301+/-86.8 nmol/L) compared with
      control subjects (mean, 490+/-132.6 nmol/L; P=.019). CONCLUSION: After subtotal
      bilateral adrenalectomy left 15% to 30% of adrenal tissue in situ, functional
      recovery could be observed in all patients. However, subclinical impairment of
      the adrenocortical function with questionable clinical significance has to be
      considered in some of the patients. Especially during the early postoperative
      period, careful observation of the patients without exogenous steroid
      administration is required.

PMID- 14668737
TI  - When should thyroidectomy be performed in familial medullary thyroid carcinoma
      gene carriers with non-cysteine RET mutations?
AB  - BACKGROUND: Once familial medullary thyroid carcinoma gene carrier status is
      established, thyroidectomy must be performed in infancy for mutations in exon 10,
      but in familial medullary thyroid carcinoma with non-cysteine RET mutations,
      which is characterized by a late onset of C-cell disease, the appropriate timing
      of thyroidectomy is unclear. METHODS: We analyzed the cases of 76 patients who
      underwent thyroidectomy (mean age, 35.2 years); 66 patients underwent concomitant
      lymphadenectomy. RESULTS: Before the operation, 35 patients had abnormal basal
      calcitonin levels. Nine and 30 patients had negative or positive pentagastrin
      test results, respectively. We found normal thyroid in 4% of the patients, C-cell
      hyperplasia in 29% of the patients, medullary thyroid carcinoma in 67% of the
      patients (microscopic in 82.4%), and nodal metastases in 19.6% of the patients.
      The aggressiveness of the disease varied significantly between those patients
      with preoperative positive pentagastrin test results and those patients with high
      basal calcitonin levels, with a surgical cure rate of 60% and 34.3%,
      respectively. All patient who did not achieve cure had high basal preoperative
      calcitonin levels, which were related to macroscopic medullary thyroid carcinoma
      and nodal metastases in 5 of 9 patients. CONCLUSION: Thyroidectomy should not be
      delayed until basal calcitonin level becomes abnormal, at which time advanced
      disease may be present. As soon as the pentagastrin stimulation test becomes
      abnormal, operation should be undertaken on early staged disease to achieve cure
      for the patient. When performed while pentagastrin stimulation test is still
      negative, thyroidectomy may be truly prophylactic and should be recommended at 5
      to 6 years.

PMID- 14668738
TI  - Negative preoperative localization studies are highly predictive of
      multiglandular disease in sporadic primary hyperparathyroidism.
AB  - BACKGROUND: The development of localization studies and quick parathyroid hormone
      assay (QPTH) has allowed the development of focused surgery in sporadic primary
      hyperparathyroidism. The aim of this investigation was to determine whether
      localization studies select a specific population of patients. METHODS: From 1999
      to 2001, 213 patients underwent surgery for sporadic primary hyperparathyroidism.
      All were investigated with sestamibi scanning and ultrasonography. When at least
      1 study showed a positive result (n=175), the patient underwent a video-assisted
      approach with QPTH. When results were negative (n=38), the patient underwent
      cervicotomy and exploratory procedures of all 4 parathyroid glands. RESULTS: All
      patients are cured (mean follow-up, 17.8+/-10.3 months [SD]). Patients with
      negative preoperative study results had a high risk of multiglandular disease
      (12/38 patients; 31,6%), compared with patients with 1 positive study result
      (3/83 patients; 3.6%; P<.0001) and those with 2 concordant positive study results
      (0/92 patients; P<.0001). CONCLUSION: When preoperative localization study
      results are negative, the patient has a high risk of multiglandular disease, and
      a conventional cervicotomy with identification of the 4 glands is recommended
      strongly. When only 1 localization study is positive, the risk of multiglandular
      disease justifies the use of QPTH during a focused approach. When positive
      localization study results are concordant, the use of QPTH is questionable during
      a focused approach.

PMID- 14668739
TI  - Loss of heterozygosity of the VHL gene identifies malignancy and predicts death
      in follicular thyroid tumors.
AB  - BACKGROUND: Follicular thyroid tumors (FTT) usually require resection to
      distinguish adenoma from carcinoma. Better markers that predict histologic
      subtype and prognosis are needed for FTT. METHODS: Seventeen benign and malignant
      FTT with follow-up were selected. Pathologic diagnosis was confirmed, tumor and
      normal tissue were microdissected, and DNA was extracted. Polymerase chain
      reaction (PCR) products for a microsatellite marker at the von Hippel Lindau gene
      (VHL) gene locus (3p26) were analyzed with semiquantitative capillary gel
      electrophoresis to detect loss of heterozygosity (LOH). Data were assessed for
      statistical significance with chi(2). RESULTS: Mean follow-up was 77 months
      (range 29 to 120 months). Four cases were uninformative (homozygous
      microsatellite). Among 13 evaluable patients (6 adenomas, 7 follicular cancers)
      LOH of VHL was present only in carcinomas (P=.013). LOH was present in 4/4
      patients with recurrence and 0/3 patients without recurrence (P=.017). Death from
      disease has occurred in 3 patients. LOH of VHL was strongly associated with death
      from disease (P=.034). CONCLUSIONS: FTT can be analyzed for LOH at the VHL gene
      locus. In this initial study, LOH of VHL was highly specific for malignancy and
      predicted death from disease. The analysis of VHL may provide for preoperative
      detection in cytologic samples with potential impact on clinical management of
      FTT.

PMID- 14668740
TI  - Intraoperative parathyroid hormone assay and parathyroid reoperations.
AB  - BACKGROUND: The purpose of this study was to determine whether intraoperative
      parathyroid hormone (IOPTH) assay improved results of reoperations. METHODS: One
      hundred two patients with persistent/recurrent sporadic primary
      hyperparathyroidism underwent 108 reoperations (1996-2002). IOPTH was not used
      (n=58) from 1996-1998 (group 1). IOPTH was used (n=50) from 1999-2002 (group 2).
      Sensitivity and positive predictive value of IOPTH and its influence on surgical
      strategy were analyzed. A 50% decrease occurring 10 minutes after removal of
      parathyroid tumor was used to determine if all abnormal tissue had been removed.
      RESULTS: Groups 1 (58 patients) and 2 (50 patients) were comparable except for
      duration of follow-up. The cure rate was 84% (group 1, 87%; group 2, 82%, P=0.7).
      Hypocalcemia developed in 20 patients (permanent in 2 patients). There was 1
      permanent vocal cord paralysis and 1 patient died of toxic shock syndrome. IOPTH
      successfully predicted cure in 44 of 49 patients (sensitivity, 90%); the positive
      predictive value was 90%. Values for parathyroid hormone level and the ratio
      parathyroid hormone/calcium at day 1 were at least as accurate as IOPTH in
      predicting cure. IOPTH was helpful in 1 patient but misleading in 4 patients. It
      failed to modify intraoperative strategy in most other patients. CONCLUSIONS:
      IOPTH testing was relatively reliable in patients with persistent or recurrent
      sporadic primary hyperparathyroidism, but the test unfortunately failed to
      improve the overall success rate at reoperation.

PMID- 14668741
TI  - Aggressive surgery for metastatic liver neuroendocrine tumors.
AB  - BACKGROUND: Neuroendocrine tumors of the gastrointestinal tract (carcinoids,
      pancreatic endocrine tumors) have low malignant potential but can decrease
      survival rates if they spread to the liver (LNET). METHODS: The records of 16
      patients with LNET primarily from gastrointestinal carcinoids treated surgically
      were retrospectively reviewed. RESULTS: There were 12 women and 4 men. Median age
      was 56 years (range 25 to 75). Thirteen (81%) had a carcinoid tumor and 5 had
      gastrinoma. Two patients with multiple endocrine neoplasia type 1 had both a
      gastric carcinoid and a jejunal gastrinoma. Eight patients (50%) had the
      carcinoid syndrome. Each patient had all identifiable LNET either resected or
      ablated. Ten patients had liver wedge resections, 1 right trisegmentectomy, 5
      left hepatic lobectomies, and 2 radiofrequency ablations. Thirteen (81%) patients
      had concomitant bowel resections. Two patients had concomitant total
      gastrectomies to remove stomach primaries. The final patient had an
      extraintestinal pelvic primary or a liver primary. There were no operative
      deaths, and all 8 (100%) patients with the carcinoid syndrome had amelioration of
      symptoms. The 5-year actuarial survival rate was 82% with a median follow-up of
      32 months. CONCLUSIONS: This study demonstrates that liver and concomitant
      extrahepatic surgery can be performed safely in patients with liver metastases
      because of carcinoids or pancreatic endocrine tumors. It results in excellent
      long-term survival and amelioration of symptoms. Surgery should be the first-line
      therapy for patients with LNET.

PMID- 14668742
TI  - Adrenal-preserving laparoscopic surgery in selected patients with bilateral
      adrenal tumors.
AB  - BACKGROUND: There have been few reports of laparoscopic adrenal-sparing surgery
      for bilateral adrenal tumors. We review our experience with this type of surgery
      with the aim of evaluating its feasibility and safety. METHODS: Over a 4-year
      period, we treated 9 patients with bilateral benign adrenal tumors. Seven
      patients had bilateral pheochromocytomas (MEN 2: 5, VHL: 1, sporadic: 1), and 2
      patients had Cushing's syndrome caused by bilateral adrenocortical adenomas.
      Laparoscopic procedures were performed by a flank approach. The mean diameter of
      the tumors was 3.7 cm (range, 2.0-8.5 cm). RESULTS: All the tumors were removed
      laparoscopically. Four patients with hereditary pheochromocytomas underwent
      bilateral total adrenalectomy because of the large tumor size and multiplicity.
      The other 5 patients were treated successfully with preservation of
      adrenocortical function. In 4 of these 5 patients, the adrenal tumors were 3 cm
      or less in diameter. None of the patients experienced surgical complications. At
      a mean follow-up of 16 months (range, 4-40 months), none of the 5 patients who
      were treated by adrenal-sparing surgery required corticosteroid replacement.
      CONCLUSION: Laparoscopic surgery is feasible for the treatment of bilateral
      adrenal tumors. Adrenal-preserving laparoscopic surgery may be practicable for
      the removal of these tumors, if the tumor on either side is 3 cm or less in
      diameter; however, our follow up is short (mean, 16 months).

PMID- 14668750
TI  - Single implant-supported molar and premolar crowns: a ten-year retrospective
      clinical report.
AB  - Evidence of the successful use of osseointegrated dental implants for the
      restoration of individual teeth has been reported for anterior teeth more
      frequently than for posterior teeth. Contiguous implants placed in posterior
      quadrants are often splinted without clear rationale. This clinical report
      describes the data collected from the charts of patients provided with implant
      supported single crowns in posterior quadrants in a prosthodontic practice in
      southern California. Forty-nine patients with 126 implants restored with molar or
      premolar crowns were recalled for examination after periods ranging from 6 months
      to 10 years. The implant failure rate was 4.6%, with complications of abutment
      screw loosening (7%) and loss of cement bond (22%). Osseointegrated implants in
      molar and premolar positions may be restored as single crowns.

PMID- 14668751
TI  - Restoring function and esthetics in a patient with amelogenesis imperfecta: a
      clinical report.
AB  - This clinical report describes the prosthodontic treatment for an 18-year-old man
      diagnosed with amelogenesis imperfecta. The aim of treatment was to reduce dental
      sensitivity and to restore esthetics and masticatory function. Metal-ceramic
      fixed partial dentures were placed on posterior teeth to modify the occlusion,
      and porcelain laminate veneers were placed to improve the esthetics of the
      maxillary anterior teeth. Clinical examination 12 months after treatment revealed
      no evidence of disorders associated with the restored teeth or their supporting
      structures.

PMID- 14668752
TI  - Improved edge strength in a facial prosthesis by incorporation of tulle: a
      clinical report.
AB  - This clinical report describes the use of tulle for increasing the tear
      resistance of a facial prosthesis. By incorporating tulle, a prosthesis' margins
      may be more stable, more resistant to tearing, and less likely to deform while
      adhesive, cosmetics, and cleaning agents are applied and removed.

PMID- 14668753
TI  - The use of resorbable collagen membrane in conjunction with autogenous bone graft
      and inorganic bovine mineral for buccal/labial alveolar ridge augmentation: a
      pilot study.
AB  - STATEMENT OF PROBLEM: No study provides human histologic evidence regarding the
      use of resorbable collagen membrane for a 2-stage localized alveolar augmentation
      procedure. PURPOSE: The purpose of this pilot study was to evaluate the potential
      of use of a resorbable collagen membrane in conjunction with an autogenous bone
      graft and inorganic bovine mineral (IBM) for labial/buccal alveolar ridge
      augmentation prior to placing dental implants. Material and methods Seven
      consecutively treated human patients participated in the study. All patients
      received labial/buccal alveolar ridge augmentation. An autogenous block graft was
      secured at the recipient site with fixation screws and a mixture of autogenous
      particulate with IBM was placed at the periphery. Resorbable collagen membrane
      was used as a barrier. Radiographic and laboratory measurements were made to
      quantify ridge augmentation and resorption rate. Preoperative and postoperative
      stone casts were used to quantify alveolar ridge augmentation. Volumetric
      evaluation was measured in mL whereas linear laboratory evaluation was measured
      in millimeters. Measurements were made 1 and 6 months after bone grafting.
      Histologic and histomorphometric analysis from the grafted area evaluated new
      bone formation, and osteoconductivity of IBM. RESULTS: For all patients Type II
      to III bone quality was achieved at the augmented sites. The implant survival
      rate was 100% at second-stage surgery. No complication was observed at the
      recipient sites. Radiographic evaluation revealed 4.65 mm labial/lingual
      augmentation, whereas laboratory analysis revealed 4.57 mm. Volumetric laboratory
      analysis demonstrated 1.00 (+/- 0.29) mL alveolar ridge augmentation 6 months
      after bone grafting and 13.79% resorption between months 1 and 6.
      Histomorphometric analysis revealed that on average, the area occupied by bone
      was 34.28% (range 24 to 50; +/-9.05),] soft tissue 46.00% (+/-9.20%; range 30% to
      55%), and IBM particles 19.71% (+/-11.74%, range 3% to 42%). The proportion of
      the surface of the IBM particles in contact with bone was 47.14% (range 15% to
      64%; SD 17.21%). CONCLUSIONS: Resorbable collagen membranes may be used as
      barriers for labial/buccal alveolar ridge augmentation procedures.

PMID- 14668754
TI  - Finite element analysis to determine implant preload.
AB  - STATEMENT OF PROBLEM: The nature of the forces used to clamp implant components
      together, and how they are generated and sustained, is lacking in the literature.
      PURPOSE: This study examined the dynamic nature of developing the preload in an
      implant complex using finite element analysis. METHODS: The implant complex was
      modeled in accordance with the geometric designs for the Nobel Biocare implant
      systems. A thread helix design for the abutment screw and implant screw bore was
      modeled to create the geometric design for these units of the implant systems.
      Using the software programs HyperWorks and LS3D-Dyna, 2 3-dimensional finite
      element models of (1) a Branemark System 3.75 x 10-mm titanium Mark III implant,
      a CeraOne titanium abutment, a Unigrip gold alloy abutment screw, and (2) a
      Replace Select System 4.30 x 10-mm titanium implant, a Straight Esthetic titanium
      abutment, and a TorqTite titanium abutment screw were created. Modeling the
      threads to the machining specifications permitted simulation of screw tightening.
      The abutment screws were subjected to a tightening torque in increments of 1 Ncm
      from 0 to 64 Ncm using ABAQUS software. Using these models, the effect of the
      coefficient of friction on the development of preload amount in the implant
      complex during and after abutment screw tightening was determined. In the first
      experiment, the coefficient of friction was set to 0.20 between the titanium
      bearing surface of the abutments and the implant bearing surfaces, and 0.26
      between the gold abutment screw and the titanium implant screw bore. In the
      second experiment, the coefficient of friction was varied; the titanium implant
      and titanium abutment bearing surfaces were set to a coefficient of friction of
      0.20, whereas the Mark III gold and the Replace Select titanium abutment screws
      and their respective titanium screw bores in the implants were set to 0.12. The
      preload amount (N) was determined from the finite element analysis. RESULTS: The
      stress distribution pattern clearly demonstrated a transfer of preload force from
      the screw to the implant during tightening. A preload of 75% of the yield
      strength of the abutment screw was not established using the recommended
      tightening torques. CONCLUSION: Using finite element analysis, a torque of 32 Ncm
      applied to the abutment screws in the implant assemblies studied in the presence
      of a coefficient of friction of 0.26 resulted in a lower than optimum preload for
      the abutment screws. To reach the desired preload of 75% of the yield strength,
      using a torque of 32 Ncm applied to the abutment screws in the implant assemblies
      studied, the coefficient of friction between the implant components should be
      0.12.

PMID- 14668755
TI  - In vitro assessment of retention of four esthetic dowels to resin core foundation
      and teeth.
AB  - STATEMENT OF PROBLEM: Several new esthetic dowel systems are currently available
      for the restoration of endodontically treated teeth. These dowel systems enhance
      the esthetic quality of all-ceramic restorations better than metallic dowel
      systems. PURPOSE: The purpose of this study was to evaluate the retentive
      strength of composite and ceramic endodontic dowel systems to the tooth and to
      the core foundation. MATERIAL AND METHODS: The following dowel systems were
      tested: resin dowels (Fibrekor [FR]; Luscent [LU]; Twin Luscent Anchor [TLU]);
      ceramic dowels (Cerapost [CR]; Cosmopost [CO]); and a titanium dowel (ParaPost XH
      [Ti]). In Part I of the study, core retention was tested by forming Bis-Core
      resin (n=12) cores around dowels followed by separation using a universal testing
      machine. In Part II, 60 (n=12) extracted human canines were endodontically
      treated, and dowel spaces were prepared using the corresponding drill for each
      dowel system. Nine-millimeter resin and ceramic dowels were cemented with C & B
      resin luting agent. Additionally, 2 groups (n=12) of Ti dowels cemented with C &
      B resin luting agent and zinc phosphate luting agent served as control groups.
      Retention was tested using a universal testing machine to separate the dowels
      from teeth. One-way analysis of variance and Student Newman-Keuls tests were
      conducted for statistical analysis (alpha=.05). Surface texture of all dowel
      systems tested was examined using SEM at original magnification x25 and x250.
      RESULTS: Core retention of Ti was higher than all esthetic dowels tested
      (alpha<.05), but FR had higher core retention than the other esthetic dowels
      tested. Resin dowels had better retention to teeth than ceramic dowels
      (alpha<.05). CONCLUSION: The esthetic dowel systems were less retentive for the
      resin core material than the titanium control. Resin dowel systems were more
      retentive in the root than the ceramic dowels but were similar to the titanium
      control.

PMID- 14668756
TI  - Factors determining post selection: a literature review.
AB  - Most endodontically treated teeth require a post-and-core build-up for restoring
      the teeth to optimum health and function. Selection of an appropriate post-and
      core system from the wide variety of those available may be a clinical dilemma.
      Therefore, the purpose of this article is to review the literature to identify
      the various factors that influence the selection of the post-and-core assembly.
      English-language peer-reviewed articles between 1961 and 2002 were identified
      using MEDLINE, as well as a hand search. The following key words were used: post,
      design, retention, fracture resistance, survivability, and esthetics. Selection
      of a post and core system should satisfy many interrelated biologic, mechanical,
      and esthetic factors to optimally restore the endodontically treated tooth to
      adequate form and function. This review may serve as a guide to aid the clinician
      in the selection of a post-and-core system.

PMID- 14668757
TI  - The influence of porcelain layer thickness on the final shade of ceramic
      restorations.
AB  - STATEMENT OF PROBLEM: Ceramic restorations should be made of porcelain layers of
      different opacity, shade, and thickness in order to provide a natural appearance.
      By means of CAD/CAM layering technology such as CICERO, it is feasible to produce
      all-ceramic crowns with porcelain layers of predetermined thickness. However, it
      is not yet known whether changes in thickness of these porcelain layers within
      the clinically available space can perceivably influence the overall shade of the
      restoration. PURPOSE: The purpose of this study was to determine, quantitatively,
      the effect of different thickness ratios of opaque porcelain (OP) and translucent
      porcelain (TP) layers on the overall shade of all-ceramic specimens. MATERIAL AND
      METHODS: The CIELAB values of 5 assembled specimens, each consisting of 2 or 3
      discs (CORE 0.70 mm/OP--0, 0.25, 0.50, 0.75, or 1.00 mm/TP 1.00, 0.75, 0.50,
      0.25, or 0 mm) were determined with a spectrophotometer for the Vita shades A1,
      A2, and A3. Distilled water was used to attain optical contact between the
      layers. Black or white backgrounds were used to assess the influence of the
      background on the final shade. Color differences (DeltaE) between layered
      specimens were determined. Correlation between the thickness ratio and the L*,
      a*, and b* values was calculated by 2-tailed Spearman correlation analysis.
      RESULTS: The results indicated that small changes in OP/TP thickness ratio can
      perceivably influence the final shade of the layered specimens (DeltaE>1).
      Redness a* and yellowness b* increased with the thickness of OP for all shades.
      Redness a* (P<.01 for all shades) correlated more strongly with thickness than
      yellowness b* (P<.01 for A1 and A3; P<.05 for A2). The lightness (L*) was shade
      dependent. The correlation (r) between OP/TP thickness and L* was 0.975 (P<.01)
      for shade A1, 0.700 (not statistically significant) for shade A2, and 0.900
      (P<.05) for shade A3. CONCLUSION: Small changes in thickness and shade of opaque
      and translucent porcelain layers can influence the final shade of the layered
      porcelain specimen.

PMID- 14668758
TI  - Attitudes of Saudi male patients toward the replacement of teeth.
AB  - STATEMENT AND PROBLEM: [corrected] The objective of tooth replacement is the
      restoration of esthetics and function. Patient perceptions of esthetic and
      functional needs may not match the dental professional's assessment of these
      needs. PURPOSE: The objective of this study was to investigate the relationship
      between patient perceptions and professional assessments of prosthetic treatment
      needs in a population limited to Saudi men. MATERIAL AND METHODS: The study
      population comprised 238 Saudi Arabian men between the ages of 16 and 77.
      Subjects were classified in accordance with 3 parameters: age (16-25, 26-35, 36
      45, or >45 years); completed education (primary, high school, or higher
      education); and number of missing teeth (1, 2-3, 4-6, or >6). A structured
      interview was conducted and each subject was asked 3 closed-ended (yes/no)
      questions on tooth loss and its effects. The interview was followed by a dental
      examination in which each subject's dental status and normative treatment needs
      were assessed. Patient perception data were compared to professionally assessed
      need. Data were analyzed with McNemar's test (alpha=.05). RESULTS: Overall, 82%
      (194) of subjects expressed the need to replace their missing teeth. Forty-four
      percent (105) believed that tooth loss negatively affected their appearance, and
      63% (150) thought that tooth loss reduced their chewing efficiency. The
      discrepancy between perceived and professionally assessed need in regard to
      function was significant (P<.01). CONCLUSION: Within the limitations of this
      study, subjective perceptions of esthetic and functional treatment needs were
      highly variable among the Saudi male patients evaluated. Patient perceptions
      could not be predictably estimated by professionally assessed clinical need.

PMID- 14668759
TI  - Comparison of fracture tests of denture base materials.
AB  - STATEMENT OF PROBLEM: Clinical studies have shown midline fracture to be a common
      problem in dentures. In order to evaluate the resistance of denture base resins
      against fracture, not only impact strength measurements but also fracture
      toughness tests should be performed. PURPOSE: The aim of this study was to
      determine the fracture toughness of denture base resins and to compare the
      results with impact strength measurements. MATERIALS AND METHODS: Seven heat
      polymerized denture base resins were chosen for the study: 5 high impact (GC
      Luxon, Injectall IPF HI-I, Ivocap Plus, Lucitone 199, and Trevalon HI) and 2
      conventional (Major Base 2 and Probase Hot). Three series of 12 specimens were
      used for the Charpy impact test (specimen dimensions: 80 x 10 x 4 mm, notch
      depth: 2 mm) and 2 Izod impact tests (specimen dimensions: 50 x 6 x 4 mm; notch
      depth: 1.2 mm for the first series, 3.4 mm for the second series). The maximum
      stress intensity factor (K(I,max)) (MPa.m(1/2)) and the work of fracture (WOF)
      (kJ/m2) were measured for 8 specimens in a fracture toughness test (specimen
      dimensions: 40 x 8 x 4; notch depth: 3.2 to 3.3 mm). A 1-way ANOVA with a post
      hoc Tukey-Kramer test (alpha=.05) was used to compare the data. RESULTS: The
      results achieved by the different materials and the rankings varied, depending on
      which parameter was considered. For example, the 1.2-mm Izod impact strength of
      Ivocap Plus (2.49 +/- 0.24 kJ/m2) was not significantly different from GC Luxon
      (2.64 +/- 0.15 kJ/m2) and significantly higher than Major Base 2 (1.99 +/- 0.23
      kJ/m2) and Probase Hot (1.79 +/- 0.20 kJ/m2) (P<.001). On the other hand, the
      Charpy impact strength of Ivocap Plus (1.47 +/- 0.16 kJ/m2) was almost half the
      value of GC Luxon (2.85 +/- 0.05 kJ/m2) and not significantly different from
      Major Base 2 (1.36 +/- 0.03 kJ/m2) and Probase Hot (1.36 +/- 0.09 kJ/m2). In the
      fracture toughness test, the K(I,max) values of GC Luxon (2.63 +/- 0.09
      MPa.m(1/2)), Lucitone 199 (2.53 +/- 0.08 MPa.m(1/2)), Trevalon HI (2.56 +/- 0.13
      MPa.m(1/2)), and Ivocap Plus (2.41 +/- 0.04 MPa.m(1/2)) were not significantly
      different. Among all parameters, the WOF value appeared to be the test that
      allowed a clear differentiation between the products, placing Probase Hot (0.27
      +/- 0.03 kJ/m2) and Major Base 2 (0.38 +/- 0.03 kJ/m2) on a low level, Injectall
      IPF HI-I (0.63 +/- 0.17 kJ/m2) on an intermediate level, Ivocap Plus (1.12 +/-
      0.06 kJ/m2) on a medium-high level, and Lucitone 199 (1.41 +/- 0.06 kJ/m2), GC
      Luxon (1.50 +/- 0.17 kJ/m2), and Trevalon HI (1.58 +/- 0.07 kJ/m2) on a high
      level. CONCLUSION: Specimen geometry and testing configuration influenced the
      impact strength measurements. The fracture toughness method seems to be more
      suitable than impact strength measurements to demonstrate the effects of resin
      modifications. The differences between conventional and so-called "high-impact"
      denture base resins are more clearly demonstrated with fracture toughness
      measurements.

PMID- 14668760
TI  - In vitro deformation of acetyl resin and metal alloy removable partial denture
      direct retainers.
AB  - STATEMENT OF THE PROBLEM: Acetyl resin removable partial denture (RPD) direct
      retainers may provide an esthetic alternative to conventional metal direct
      retainers. The effect of repeated stress on acetyl resin direct retainers is
      unknown. PURPOSE: This study compared deformation of acetyl resin and metal alloy
      RPD direct retainers after repeated dislodgments over a test die. MATERIAL AND
      METHODS: Ten acetyl resin (Thermoflex) and 10 metal alloy (Ticonium Premium 100)
      RPD direct retainers, fabricated to manufacturers' specifications, were dislodged
      over a stainless steel die by means of a laboratory test apparatus for a
      simulated 3-year period (5000 cycles). Occlusal and facial digital images made
      before and after cycling were measured (mm) for direct retainer deformation by
      using computer-imaging software (Scion Image 1.62). Student t tests (alpha=.05)
      were performed for statistical comparisons. RESULTS: A significant difference in
      deformation between acetyl resin and metal alloy direct retainers occurred in the
      occlusal view (P=.045), but not in the facial view (P=.832). Average deformation
      varied but was greatest in the occlusal view: 0.09 +/- 0.8 mm for acetyl resin
      direct retainers compared with 0.01 +/- 0.9 mm for metal alloy direct retainers.
      Average facial view deformations revealed no significant differences: 0.039 +/-
      0.6 mm for metal alloy and 0.033 +/- 0.7 mm for acetyl resin direct retainers.
      CONCLUSION: Within the limitations of this in vitro study, significantly greater
      deformation resulted with acetyl resin compared with metal alloy direct retainers
      after 3 years of simulated use.

PMID- 14668761
TI  - Finite element analysis of stresses in molars during clenching and mastication.
AB  - STATEMENT OF PROBLEM: During physiological functions of the masticatory system
      such as swallowing and chewing, teeth are subjected to variations in force
      application. Most in vitro analyses of stress have not analyzed the combined
      forces acting on teeth. PURPOSE: The purpose of this study was to analyze the
      stresses induced in a mandibular molar during clenching and chewing of morsels
      with various elastic moduli. MATERIALS AND METHODS: The investigation was
      performed by means of finite element analysis with the use of contact elements.
      Two-dimensional models of the mandibular first molar and the crown of the
      opposing maxillary molar were created. The computerized simulation evaluated the
      clenching and chewing of 4 morsels with different elastic moduli (similar to hard
      gum, tough meat, bone, and combination of hard gum and bone). The movement of the
      studied teeth was simulated in the frontal plane. Teeth models crushed morsels
      and closed into the maximal intercuspation position. The values of stresses in
      the mandibular molar were calculated during these situations. RESULTS: The study
      revealed that clenching of molars and chewing morsels of high elastic moduli
      resulted in maximal equivalent stresses within occlusal enamel. During
      mastication of morsels of low elastic moduli the stress concentration was located
      in the cervical region of the lingual side of the mandibular molar. Masticating a
      low-elasticity morsel containing a fragment of bone caused the highest equivalent
      stresses in the lingual wall and high tensile stresses in enamel near the central
      intercuspal fissure of the tooth studied. CONCLUSION: During mastication of
      various morsels, maximal equivalent stresses occurred in occlusal enamel and in
      the cervical region of the lingual wall of the first mandibular molar. The more
      unfavorable and highest stresses were exerted during mastication of
      nonhomogeneous morsels.

PMID- 14668762
TI  - Use of casting tape for support of an extraoral impression.
AB  - This article describes a technique for using casting tape to support irreversible
      hydrocolloid material when making extraoral impressions to increase patient
      comfort, save time, and produce less tissue distortion.

PMID- 14668763
TI  - Laboratory-processed acrylic resin provisional restoration with cast metal
      substructure for immediately loaded implants.
AB  - Most methods of immediate loading of implants reported in the literature involve
      retrofitting a pre-existing denture to the implants. This article describes and
      illustrates clinical and laboratory procedures for immediate loading of implants
      in the edentulous mandible with the use of a laboratory-processed, provisional,
      screw-retained, implant-supported fixed complete denture that incorporates a cast
      metal reinforcement.

PMID- 14668764
TI  - Fabrication of occlusal device for protection of implant overdenture abutments
      with O-ring attachments.

PMID- 14668765
TI  - Anterior deprogramming device fabrication using a thermoplastic material.
AB  - This article presents a simple and efficient technique to fabricate an anterior
      deprogramming device using a thermoplastic material. The material, softened by
      heating, is adapted to the maxillary incisors while moldable. The operator guides
      the mandible into closure as the material stiffens. The device is then trimmed,
      and a posterior centric relation record is made using the recording material of
      choice.

PMID- 14668766
TI  - Using a supporting base for complete or removable partial denture definitive
      impressions.

PMID- 14668767
TI  - Use of a feeler gauge to measure the gap between adjacent teeth.

PMID- 14668769
TI  - Activity of the uptake-1 norepinephrine transporter as measured by I-123 MIBG in
      heart failure patients with a loss-of-function polymorphism of the presynaptic
      alpha2C-adrenergic receptor.
AB  - BACKGROUND: Patients with a deletion of 4 consecutive amino acids in the gene
      encoding for the alpha(2C)-adrenergic receptor (alpha(2C)Del322-325) have an
      increased prevalence of clinical heart failure, worse clinical status, and a
      lower left ventricular ejection fraction compared with patients without this
      deletion. We postulated that patients with the alpha(2C)Del322-325 polymorphism
      would have a compensatory increase in norepinephrine uptake-1 transporter
      activity as measured by iodine 123 metaiodobenzylguanidine (MIBG). METHODS AND
      RESULTS: Thirty-nine patients with heart failure related to idiopathic dilated
      cardiomyopathy were studied. Demographic characteristics, left ventricular
      ejection fraction, maximum oxygen consumption, exercise duration, and plasma
      norepinephrine levels did not differ between patients with the alpha(2C) receptor
      polymorphism (n = 9) and those without it (n = 30). Patients with the
      alpha(2C)Del322-325 polymorphism had significantly greater heart-to-mediastinum
      ratios of I-123 MIBG at 4 hours after tracer injection (1.60 +/- 0.19 vs 1.41 +/-
      0.19, P =.0117) and greater background-corrected heart counts per pixel at 4
      hours compared with patients without the polymorphism. CONCLUSIONS: Patients with
      genetic impairment of the alpha(2C)-adrenergic receptor have augmented activity
      of the norepinephrine uptake-1 transporter as measured by I-123 MIBG. Further
      studies are needed to clarify the mechanism by which uptake-1 transporter
      activity is increased in this setting.

PMID- 14668770
TI  - Coronary calcium screening in asymptomatic patients as a guide to risk factor
      modification and stress myocardial perfusion imaging.
AB  - BACKGROUND: Previous studies have demonstrated a correlation between the extent
      of coronary artery calcification (CAC) and atherosclerotic plaque. As a result,
      CAC screening could be useful in predicting cardiovascular risk in individuals in
      whom atherosclerosis is developing. One possible method of detecting and
      quantifying CAC is by x-ray computed tomography, which potentially allows one to
      stratify patients into groups requiring risk factor modification or follow-up
      testing such as myocardial perfusion single photon emission computed tomography
      (SPECT). METHODS AND RESULTS: This study was designed to evaluate the clinical
      utility of multidetector computed tomography (MDCT) in a cardiology practice
      setting. A retrospective analysis was performed on data from 794 asymptomatic
      patients who underwent CAC screening over an 8-month period. On the basis of the
      CAC score and physician consultation, 102 patients underwent subsequent
      myocardial perfusion SPECT imaging. A substudy was also conducted in 306 patients
      to measure the interscan variability of MDCT across different CAC score ranges.
      CAC was detected in 422 of 794 patients. Of these, the CAC was moderate (Agatston
      score = 101-400) in 14% and severe (>400) in 9%. Patients with 3 or more cardiac
      risk factors were most likely to exhibit moderate to severe CAC. In myocardial
      perfusion SPECT testing, no patient with an Agatston score lower than 100 had an
      abnormal study. In contrast, 41% of patients with severe CAC had an abnormal
      SPECT study. In the reproducibility substudy the minimal CAC group had the
      largest variability (86.0%) whereas the severe CAC group had the lowest
      variability (9.5%). CONCLUSION: CAC screening with MDCT is justified for
      asymptomatic patients with 3 or more cardiac risk factors. However, risk factor
      assessment is poor at predicting which individuals will have CAC if fewer risk
      factors are present. In terms of the interscan variability, MDCT is capable of
      following changes in CAC for patients with Agatston scores greater than 100.
      Finally, this study demonstrated that an Agatston score of 400 is a logical
      threshold to initiate follow-up myocardial perfusion SPECT testing.

PMID- 14668772
TI  - Myocardial contractile reserve determined by dobutamine stress Tc-99m tetrofosmin
      quantitative gated SPECT predicts late spontaneous improvement in cardiac
      function in patients with recent-onset dilated cardiomyopathy.
AB  - BACKGROUND: We evaluated whether dobutamine stress technetium 99m tetrofosmin
      (DSTF) quantitative gated single photon emission computed tomography (QGS) could
      predict late spontaneous improvement of cardiac function in patients with
      idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: The study included
      26 patients with recently diagnosed (<2 months) idiopathic DCM and a left
      ventricular ejection fraction (LVEF) lower than 45%. DSTF-QGS was performed in
      all patients to measure LVEF at rest and during dobutamine infusion (10 microg.
      kg(-1). min(-1)). LVEF and left ventricular end-diastolic volume (LVEDV) were
      determined by echocardiography, and New York Heart Association (NYHA) functional
      class was estimated at baseline and after 1 year. After 1 year of treatment, the
      echocardiographic LVEF improved by greater than 5% in 13 patients (group A) but
      did not improve in the remaining 13 patients (group B). At baseline, the
      echocardiographic LVEF, LVEDV, and NYHA functional class were similar in both
      groups. However, there was a greater increase in the LVEF during the dobutamine
      infusion portion of the DSTF-QGS (DeltaLVEF) in group A than in group B (13.1% +/
      5.9% vs 2.6% +/- 4.1%, P <.0001). If a critical value for the DeltaLVEF of 7.0%
      was used to predict improvement in LVEF after treatment, the sensitivity was
      84.7% and the specificity was 84.7%. LVEDV and NYHA functional class improved to
      a greater extent in group A than in group B. CONCLUSIONS: DSTF-QGS can be used to
      predict late spontaneous improvement in cardiac function and symptoms after
      treatment in patients with idiopathic DCM.

PMID- 14668771
TI  - Tc-99m tetrofosmin tomography after nitrate administration in patients with
      ischemic left ventricular dysfunction: relation to metabolic imaging by PET.
AB  - BACKGROUND: In patients with ischemic left ventricular (LV) dysfunction,
      myocardial perfusion imaging after nitrate administration may improve the
      identification of dysfunctional but viable myocardium. This study was designed to
      assess the relationship between tetrofosmin uptake after nitrate administration
      and metabolic activity as assessed by positron emission tomography (PET) in
      patients with ischemic LV dysfunction. METHODS AND RESULTS: Thirty-six patients
      with chronic myocardial infarction and LV dysfunction (ejection fraction, 35% +/-
      6%) underwent resting technetium 99m tetrofosmin single photon emission computed
      tomography (SPECT) imaging under control conditions (baseline) and after
      sublingual administration of 10 mg isosorbide dinitrate. Within 1 week, all
      patients underwent metabolic PET imaging with fluorine 18-fluorodeoxyglucose.
      Tetrofosmin uptake and metabolic activity were measured in 13 segments/patient.
      Regional LV function was assessed in corresponding segments by echocardiography.
      On baseline tetrofosmin imaging, 53 (40%) of the 131 akinetic or dyskinetic
      segments had reduced (<55% of peak activity) tracer uptake. Of these segments, 14
      (26%) showed enhanced tetrofosmin uptake after nitrate administration (>/=10% vs
      baseline) and the remaining 38 (74%) did not change. The sensitivity and
      specificity of baseline tetrofosmin SPECT for detecting preserved metabolic
      activity were 69% and 86%, respectively. After nitrate administration, the
      sensitivity was higher (81%, P <.05 vs baseline) whereas the specificity was not
      different (86%, P = not significant). Concordance between tetrofosmin SPECT and
      PET in differentiating viable and necrotic myocardium was observed in 94 (72%) of
      the 131 akinetic or dyskinetic segments at baseline (kappa = 0.35) and in 108
      segments (82%) after nitrate administration (kappa = 0.53). CONCLUSIONS: After
      nitrate administration, tetrofosmin uptake in dysfunctional segments correlated
      with metabolic activity as assessed by fluorodeoxyglucose PET imaging better than
      baseline. Thus tetrofosmin SPECT after nitrate administration may improve the
      identification of ischemic but still viable myocardium in patients with chronic
      ischemic LV dysfunction.

PMID- 14668773
TI  - Risk stratification of patients after myocardial revascularization by stress Tc
      99m tetrofosmin myocardial perfusion tomography.
AB  - BACKGROUND: The aim of this study was to assess the incremental prognostic value
      of stress technetium 99m tetrofosmin imaging after myocardial revascularization.
      METHODS AND RESULTS: We studied 381 patients (aged 60 +/- 10 years, 270 men), 4.5
      +/- 3.2 years after myocardial revascularization (coronary artery bypass grafting
      in 201 patients and percutaneous coronary intervention in 180 patients), who
      underwent exercise or dobutamine stress tetrofosmin single photon emission
      computed tomography. Events during a mean follow-up period of 3.5 +/- 1.4 years
      were cardiac death in 22 patients, nonfatal myocardial infarction in 11 patients
      (33 hard cardiac events), and late revascularization in 50 patients. There was no
      incidence of hard cardiac events in the 100 patients with normal perfusion. Hard
      cardiac events occurred in 19% of patients with reversible perfusion
      abnormalities and in 4% of patients without them (P <.01). The incidence of hard
      cardiac events was similar in patients with and without angina before stress
      testing (17/197 [8.6%] vs 16/184 [8.7%]). In a multivariate analysis model,
      predictors of cardiac death were stress rate pressure product and abnormal
      perfusion. Reversible perfusion abnormalities were independently associated with
      the composite endpoints of cardiac death, nonfatal myocardial infarction, and
      late revascularization. In an incremental multivariate analysis model, an
      abnormal scan was additive to clinical data in the prediction of hard cardiac
      events (model chi(2) = 17 vs 11, P <.01). CONCLUSION: Stress Tc-99m tetrofosmin
      myocardial perfusion imaging provides independent prognostic information for the
      prediction of cardiac events after myocardial revascularization. Symptoms are not
      predictive of outcome, and therefore asymptomatic patients should not be deferred
      from stress testing. A normal study identifies a very low-risk population in whom
      no further intervention is required.

PMID- 14668774
TI  - Effect of collimator choice on quantitative assessment of cardiac iodine 123 MIBG
      uptake.
AB  - BACKGROUND: Quantitative accuracy in iodine 123 studies may be impaired by septal
      penetration. We evaluated the effect of collimator choice on estimation of the
      heart-to-mediastinum (H/M) ratio in cardiac I-123 metaiodobenzylguanidine (MIBG)
      imaging. METHODS AND RESULTS: A low-energy high-resolution (LEHR) collimator,
      special LEHR (SLEHR) collimator, and medium-energy (ME) collimator were used. In
      experiments in which a phantom of simple geometry was used, the use of the LEHR
      collimator provided the lowest contrast accuracy, suggesting the effect of septal
      penetration. Thoracic phantom studies demonstrated contamination of heart and
      mediastinum counts by lung and liver activities, which was greatest with the LEHR
      collimator and least with the ME collimator. In 8 patients anterior chest views
      were acquired successively with the three collimators after I-123 MIBG injection.
      H/M ratios were significantly higher with the SLEHR collimator than with the LEHR
      collimator and were still higher with the ME collimator. The difference in H/M
      ratios between the LEHR and ME collimators showed a high positive correlation
      with the lung-to-mediastinum ratio. CONCLUSIONS: Collimator choice substantially
      influences estimation of the H/M ratios in cardiac I-123 MIBG imaging. The use of
      an ME collimator provides high quantitative accuracy and may enhance reliability
      in the evaluation of cardiac sympathetic nerve function.

PMID- 14668775
TI  - The suitability of gamma camera coincidence systems for nitrogen 13-labeled
      ammonia myocardial perfusion imaging: a quantitative comparison with full-ring
      PET.
AB  - BACKGROUND: The aim of this study was to examine the quality of nitrogen 13
      labeled ammonia (NH(3)) perfusion data from coincidence-capable gamma camera
      positron emission tomography (GC-PET) systems compared with that from full-ring
      positron emission tomography (FR-PET). METHODS AND RESULTS: The performance
      parameters of the GC-PET system were examined and found adequate for imaging at
      the activity levels used clinically. We studied 15 patients who underwent stress
      and rest N-13-labeled NH(3) perfusion imaging on FR-PET and GC-PET systems.
      Quantitative analysis of perfusion values showed that GC-PET uptake was
      significantly lower than FR-PET uptake in 67.6% of segments. Bland-Altman
      analysis showed that the mean difference between FR-PET and GC-PET values was
      from 5.3% to 5.9%. Stress FR-PET identified 49 segments as having impaired
      perfusion, 46 (93.9%) of which were also identified by GC-PET. Fifty-six
      additional segments were identified as abnormal by GC-PET. These findings
      indicated a general overestimation of defect size on GC-PET. Analysis of the
      degree of perfusion reduction also found that GC-PET tended to overestimate
      defect contrast. These findings are similar to those previously found by workers
      examining fluorine 18-fluorodeoxyglucose uptake by both techniques. CONCLUSIONS:
      Good concordance was shown between GC-PET and FR-PET systems for N-13-labeled
      NH(3) perfusion imaging, although further work is required to optimize the
      technique.

PMID- 14668776
TI  - Relationship between right ventricular ejection fraction and maximum exercise
      oxygen consumption: a methodological study in chronic heart failure patients.
AB  - BACKGROUND: Peak oxygen consumption at maximum exercise (peak VO(2)) predicts
      survival in chronic heart failure (CHF) patients. Right ventricular ejection
      fraction (RVEF) at rest has been reported to correlate with peak VO(2). We
      evaluated the strength and consistency of the association between peak VO(2) and
      RVEF measured by different radionuclide ventriculography (RNV) techniques in a
      prospective cohort study. METHODS AND RESULTS: In 58 consecutive CHF patients
      (mean age, 53 years; 39 patients with dilated cardiomyopathy; 48 men), upright
      symptom-limited bicycle ergometry was performed. During exercise, ventilatory and
      gas exchange data were recorded and peak VO(2) was calculated. RVEF was
      calculated by use of first-pass (FP) RNV with single and dual region of interest
      (ROI) acquisition and planar multigated acquisition (MUGA). Irrespective of the
      method used, RVEF showed no relevant correlation with the corresponding peak
      VO(2) value (r = 0.11 for FP single ROI, r = 0.06 for FP dual ROI, r = 0.16 for
      MUGA). Peak VO(2) or changes in peak VO(2) after 6 and 12 months of follow-up
      were not determined by RVEF measurements. CONCLUSION: In CHF patients no
      association was found between peak VO(2) at maximum exercise and RVEF at rest
      with different RNV techniques. Changes in exercise capacity are not reliably
      reflected by changes in RVEF measurements at rest.

PMID- 14668777
TI  - Analysis of current nuclear cardiology literature in MEDLINE database: a study of
      gated SPECT imaging using PubMed.
AB  - BACKGROUND: Easy access to relevant clinical information is necessary for
      physicians to make the best decisions for patient management. The increasing
      amount of information available has made it difficult for physicians to retrieve
      up-to-date information efficiently. We sought to determine the accessibility and
      accuracy of indexing in the nuclear cardiology literature by conducting sample
      searches in the MEDLINE database on the topic of gated single photon emission
      computed tomography (SPECT) imaging. METHODS AND RESULTS: The MEDLINE database
      was initially searched by use of both a primary and a comprehensive search
      strategy on PubMed for publications in English from 1994 to 2000. A total of 260
      papers were retrieved from the primary search and 306 additional papers from the
      comprehensive search. Only 204 of the 566 citations from the combined electronic
      searches were truly relevant to gated SPECT. The resulting specificity index
      (precision) was 36%. A hand search was conducted in 11 top journals from 1994 to
      2000. It yielded 81 additional citations that were missed by the PubMed search.
      The sensitivity index (recall) was calculated for all 11 journals. The Journal of
      Nuclear Cardiology had the highest rate of publication but the lowest rate of
      recall (44%). The clinical nuclear cardiology terminology and classifications
      were compared with the available Medical Subject Headings (MeSH) and MeSH Trees
      used for indexing in MEDLINE. CONCLUSIONS: There are 6 nuclear cardiology
      techniques, including gated SPECT and myocardial perfusion imaging, that are not
      specifically indexed in the current MEDLINE database. The lack of specific MeSH
      headings and indexing structure results in low recall and precision for retrieval
      of nuclear cardiology literature. We recommend 2 additions to the MeSH Tree
      Structure and 6 new MeSH headings.

PMID- 14668778
TI  - Rest perfusion defects in patients with no history of myocardial infarction
      predict the presence of a critical coronary artery stenosis.
AB  - BACKGROUND: The rest/stress sequence in myocardial perfusion single photon
      emission computed tomography (SPECT) (MPS) permits evaluation of rest images
      before stress testing, allowing the identification of unexpected perfusion
      defects (PDs). We sought to study the angiographic correlates of these resting
      PDs. METHODS AND RESULTS: This study comprised 139 consecutive patients with no
      history of myocardial infarction referred for MPS whose stress test was canceled
      because of the observation of unexpected resting PDs (rest group). Of these, 60
      patients (43.2%) were referred for angiography after MPS (6.0 +/- 11.5 days).
      Angiographic referral rates and results were compared with those of a diagnostic
      population (n = 3565) who demonstrated stress-induced PDs (stress group) on
      rest/stress MPS. The mean age in the rest group was 73 +/- 12.5 years, and 73%
      were men. The frequency of referral for angiography was higher in the rest group
      (43.2% vs 19.8%, P <.0001). In addition, the rest group more frequently had
      significant coronary artery disease (CAD) (>/=70%) (95% vs 80%, P =.008) and
      critical CAD (>/=90%) (80% vs 66%, P =.038). CONCLUSION: The rest/stress sequence
      for MPS enables the identification of patients with unexpected resting PD,
      usually resulting from critical CAD, in whom unnecessary stress testing can be
      avoided.

PMID- 14668779
TI  - Discrepancy between myocardial ischemia and luminal stenosis in patients with
      left internal mammary artery grafting to left anterior descending coronary
      artery.
AB  - BACKGROUND: Left internal mammary artery (LIMA) grafting to the left anterior
      descending artery (LAD) is known to have long-term patency. However, myocardial
      ischemia in the territories supplied by LIMA to LAD is still demonstrated. The
      aim of this study is to examine the relationships between the extent, location,
      and clinical outcome of myocardial ischemia in LAD territories (ILAD) by use of
      myocardial perfusion imaging (MPI) and angiographic characteristics of such a
      bypass conduit. METHODS AND RESULTS: We studied 38 consecutive patients with
      prior coronary artery bypass grafting who showed stress-induced ischemia in LIMA
      to LAD territories by MPI single photon emission computed tomography between the
      years 1996-2000. All patients underwent quantitative coronary angiography within
      6 months of the nuclear study. Single photon emission computed tomography
      parameters of ILAD were assessed by location (septum, apex, anterior, and
      anterolateral) and included extension score (1-4 per patient), severity score (0
      3 per territory), and total sum score. LIMA to LAD quantitative coronary
      angiography parameters included minimal lumen diameter, lesion length, reference
      diameter, and diameter stenosis (percentage). LAD and LIMA diameters and ratio
      (in normal segments) were determined within 10 mm proximal and distal to the
      anastomotic site. The study group was compared with 18 control subjects without
      ischemia or stenosis treated with LIMA to LAD. The patients were followed up for
      cardiac death at an interval of 3.2 +/- 1.5 years from the time of MPI testing.
      The patients' mean age was 66 +/- 12 years (31 men and 7 women); the mean period
      after surgery was 6.2 +/- 1.5 years. The ILAD distribution was as follows:
      septum, 12 (32%); apex, 20 (52%); anterior, 24 (63%); and anterolateral, 18
      (47%). The mean extension score was 1.9 +/- 1.0, and the mean total sum score was
      3.4 +/- 2.3. Of 38 patients with ILAD, only 17 (45%) had greater than 50% luminal
      stenosis (2 LIMA and 15 anastomosis or distal). Among clinical variables during
      stress testing, the prevalence of angina was significantly higher in the luminal
      stenotic patients versus patients without stenosis (P =.04). A significant
      correlation was found between anterior wall ischemia and reference diameter (r = 
      0.7, P =.002) and between total sum score and minimal lumen diameter (r = -0.48,
      P =.05). Of note, the LAD-to-LIMA ratio was significantly lower in patients with
      ILAD and without luminal stenosis compared with the control group (0.73 +/- 0.16
      vs 0.87 +/- 0.15, P =.004). Cardiac death occurred in 8 patients (21%), 5
      patients with luminal stenosis versus 3 patients without stenosis (P = not
      significant). CONCLUSIONS: In patients with LIMA to LAD anastomosis, myocardial
      ischemia could occur even without angiographic luminal stenosis and apparently
      reflects a mismatch between LAD and LIMA diameters at distal anastomotic sites.
      Regarding the similar prevalence of cardiacdeath, invasive evaluation and
      aggressive treatment are recommended in all patients with ischemia in LIMA/LAD
      territories.

PMID- 14668780
TI  - Noninvasive detection of collateral flow to the infarct-related coronary artery
      in patients after myocardial infarction by Tl-201 tomographic imaging.
AB  - BACKGROUND: The determination of viability and perfusion within the infarct zone
      in post-myocardial infarction patients has both therapeutic and prognostic
      significance. Reversibility of thallium 201 uptake within the territory of the
      infarct-related coronary artery (IRA) as shown by single photon emission computed
      tomography (SPECT) is associated with a jeopardized but viable myocardium. We
      aimed to test the hypothesis that for post-myocardial infarction patients
      undergoing Tl-201 stress-redistribution SPECT, a scintigraphic pattern of distal
      reversibility without proximal reversibility within a defect corresponding to the
      IRA territory is a marker of collateral flow to the occluded culprit artery.
      METHODS AND RESULTS: We assessed Tl-201 SPECT imaging results of 78 patients with
      IRA occlusion as demonstrated by angiography 7 +/- 1 months after myocardial
      infarction. Angiography demonstrated the presence of collateral flow in 57
      patients and its absence in 21 patients. Distal reversibility was present in 42
      of the 57 patients with collateral flow (sensitivity, 74%) and was absent in 16
      of the 21 patients without collateral flow (specificity, 76%). Collateral flow to
      the IRA was demonstrated in 42 of 47 patients with distal reversibility (group A)
      (positive predictive value, 89%) and absent in 16 of 31 patients with a fixed
      defect without reversibility (group B) (P <.001) (negative predictive value,
      52%). CONCLUSIONS: In patients after myocardial infarction, a Tl-201 SPECT
      redistribution pattern of distal reversibility without proximal reversibility
      within a defect in the IRA territory is a noninvasive marker of collateral flow
      to the culprit artery with a high positive predictive value that may provide
      valuable information on patient management. A larger prospective study in an
      unselected patient population is needed to further evaluate the clinical value of
      this marker.

PMID- 14668781
TI  - Utility of stress myocardial perfusion imaging performed before
      electrophysiologic testing.
AB  - BACKGROUND: Patients considered for electrophysiologic study (EPS) are often
      first referred for stress myocardial perfusion scintigraphy (MPS) to assess for
      inducible ischemia before testing. The purpose of this investigation was to
      determine the utility of this approach by examining the relationship between MPS
      and any interim cardiac catheterization and revascularization, as well as the
      results and safety of EPS. METHODS AND RESULTS: All patients undergoing EPS
      within 30 days after MPS at our institution between January 1997 and June 2000
      were studied. Two hundred fifty-one patients met the inclusion criteria. The
      incidence of inducible sustained monomorphic ventricular tachycardia at EPS (IND)
      was 16%. One hundred twenty-nine patients had MPS ischemia (83 with high-risk
      features), but only twelve patients in all underwent revascularization between
      MPS and EPS. There were no ischemic complications during EPS. The presence of
      isolated ischemia on MPS was associated with a low rate of IND, not different
      from normal MPS findings (2%-3%). The combination of infarct and ischemia on MPS
      was associated with a high rate of IND that was similar to infarct alone (34% and
      50%, respectively; P =.28). CONCLUSIONS: Patients with high-risk MPS results are
      more likely to undergo revascularization before EPS than patients with low-risk
      or normal MPS results. However, most patients with high-risk MPS results undergo
      EPS without interim revascularization, and no patient had an ischemia-related
      complication at EPS. Larger studies will be required to confirm this observation.
      MPS infarct, not ischemia, is associated with IND at EPS.

PMID- 14668782
TI  - The perfusable tissue index: a marker of myocardial viability.

PMID- 14668783
TI  - Coronary calcium scoring: what does it really mean?

PMID- 14668784
TI  - The quest for myocardial viability: Is there a role for nitrate-enhanced imaging?

PMID- 14668785
TI  - A conceptual paradox of MIBG uptake in heart failure: retention with
      incontinence!

PMID- 14668786
TI  - American society of nuclear cardiology consensus statement: reporting of
      radionuclide myocardial perfusion imaging studies.

PMID- 14668787
TI  - Impact of gating errors with electrocardiography gated myocardial perfusion
      SPECT.

PMID- 14668788
TI  - Hiatal hernia detected by Tc-99m tetrofosmin SPECT.

PMID- 14668789
TI  - Leishmaniasis host response loci (lmr1-3) modify disease severity through a
      Th1/Th2-independent pathway.
AB  - The severity of disease caused by infection with Leishmania major depends
      critically on the genetics of the host. Early induction of T helper (Th)1-type
      immune responses in the resistant C57BL/6 mice and Th2-type responses in the
      susceptible BALB/c mice are thought to determine cure or disease, respectively.
      We have previously mapped three host response loci in a genetic cross between
      C57BL/6 and BALB/c mice, and here we show definitively the involvement of these
      loci in disease severity using animals congenic for each of the loci.
      Surprisingly, in the late stage of infection when the difference in disease
      severity between congenic and parental mice was most pronounced, their cytokine
      profile correlated with the genetic background of the mice and not with the
      severity of disease. This indicates that the loci that we have mapped are acting
      by a mechanism independent of Th phenotype.

PMID- 14668790
TI  - Generation of a functional, soluble tapasin protein from an alternatively spliced
      mRNA.
AB  - The loading of newly synthesised MHC class I molecules (MHCI) with peptides
      requires the involvement of several endoplasmic reticulum (ER)-resident cofactors
      including calnexin, calreticulin, transporter associated with antigen processing,
      ERp57 and tapasin. In the absence of tapasin, MHC I complexes are loaded with
      suboptimal peptides and their recognition by cytotoxic T cells raised to high
      affinity, immunodominant peptide epitopes is impaired. Here, we describe the
      cloning and functional assessment of an alternative spliced form of tapasin. From
      the EST database, we obtained a partially spliced tapasin cDNA that retained
      introns 4-6. When transfected into the tapasin-deficient cell line 0.220, the
      cDNA produced an alternatively spliced tapasin transcript that contained intron 5
      (74 bp). This introduced a new stop codon that terminated translation immediately
      before the putative transmembrane domain and led to a tapasin molecule containing
      the lumenal domain plus 8 extra novel amino acids at its C-terminus. This
      molecule promoted peptide loading of HLA-B5 in 0.220 cell line, and restored
      normal HLA-B5 surface expression. However, the peptides loaded onto HLA-B5 were
      suboptimal compared to those loaded onto HLA-B5 in the presence of wild-type
      tapasin.

PMID- 14668791
TI  - Pharmacogenomics and clinical medicine: passing flirtation or marriage?

PMID- 14668793
TI  - Arsenic enhances the activation of Stat1 by interferon gamma leading to
      synergistic expression of IRF-1.
AB  - Arsenic trioxide (As2O3) can induce clinical remission in patients with acute
      promyelocytic leukemia (APL), including those who have relapsed after treatment
      with all-trans-retinoic acid (RA). In vitro studies with the APL-derived NB4 cell
      line showed that As2O3 exerts a dose-dependent dual effect, which induces
      apoptosis at 1 microM, whereas at a lower concentration of 0.1 microM, a partial
      differentiation of APL is observed. In non-APL cells, interferon (IFN) alpha and
      1 microM As2O3 act synergistically to induce apoptosis. In this report, we show
      that in NB4 cells and in two RA-resistant NB4-derived cell lines, NB4-R1 and NB4
      R2, IFNalpha or IFNgamma combined with 0.1 microM As2O3 lead to an increased
      maturation effect. Moreover, IFNgamma alone is able to differentiate RA-sensitive
      and -resistant cells with a higher maturation effect on NB4-R2 cells. In
      contrast, all these cells underwent apoptosis in the presence of the cytokine and
      a higher concentration of As2O3. IFNgamma boosted As2O3-induced apoptosis in APL
      cells as tested by TUNEL, Annexin V staining and activation of caspase 3. As2O3
      differently altered IFN-induced gene products; it downregulated PML/RARalpha and
      PML, did not alter PKR and Stat1, and upregulated interferon regulatory family
      (IRF)-1. Synergism by IFNgamma and arsenic on IRF-1 expression is mediated by a
      composite element in the IRF-1 promoter that includes an IFNgamma-activation site
      (GAS) overlapped by a nonconsensus site for nuclear factor kappa B (NFkappaB).
      Arsenic has no effect on NFkappaB, whereas it enhances the activation of Stat1 by
      IFNgamma in NB4 cells leading to an increase in IRF-1 expression.

PMID- 14668794
TI  - CD95/Fas signaling in human melanoma cells: conditional expression of CD95L/FasL
      overcomes the intrinsic apoptosis resistance of malignant melanoma and inhibits
      growth and progression of human melanoma xenotransplants.
AB  - The significance of CD95/Fas ligand expression by melanoma cells has remained a
      controversial matter in recent years. On the other hand, CD95 activation may
      represent a powerful tool for eliminating tumor cells. Here, we demonstrate
      expression of CD95 in 15/17 human melanoma cell lines analysed, but complete lack
      of CD95 ligand (CD95L). Overexpression of CD95 in a tetracycline-inducible
      expression system enhanced melanoma cell sensitivity to CD95 ligation but was
      unable to trigger apoptosis by itself. In clear contrast, all melanoma cells
      tested responded with increased apoptosis to conditional expression of CD95L (2
      10-fold), both after transient and after stable transfection. Activation of
      caspase-8, Bid cleavage, cytochrome c release and caspase-3 activation followed
      after CD95L induction indicating a functional CD95-signaling cascade. CD95L was
      also able to enhance the proapoptotic effect of chemotherapeutics applied in
      parallel. Nude mouse experiments revealed that tumorigenicity was lost when
      melanoma xenografts were triggered to express CD95L. In addition, further
      progression of pre-existing melanomas was inhibited and even regression was seen
      after induction of CD95L expression. Due to these data, transfection of CD95L
      proofs as a highly efficient tool against melanoma cells in vitro and in vivo,
      and targeted expression of CD95L may thus represent a suitable strategy for
      melanoma therapy.

PMID- 14668795
TI  - Retinoic acid receptor alpha and retinoid-X receptor-specific agonists
      synergistically target telomerase expression and induce tumor cell death.
AB  - Retinoids modulate growth and differentiation of cancer cells through activation
      of gene transcription via the nuclear retinoic-acid receptors (RAR) and retinoid
      X receptors (RXR). Their use in differentiation therapy of acute promyelocytic
      leukemia (APL) represents a model concept for reprogramming cancer cells.
      However, they also regulate antiproliferative genes whose functions do not
      mechanistically concur to this program. Recently, we have shown that,
      independently of maturation, a long-term all-trans retinoic acid (ATRA) treatment
      of the maturation-resistant APL cell line (NB4-LR1) represses telomerase (hTERT),
      leading to telomere shortening and death. Using retinoid-receptor-specific
      agonists, we demonstrate herein that cross-talk between RARalpha and RXR dual
      liganded to their respective agonists resulted in strong synergistic
      downregulation of hTERT and subsequent cell death. Importantly, unlike ATRA, this
      synergy was obtained at very low agonist concentrations and occurred in other
      ATRA maturation-resistant APL cells. These findings provide the first
      demonstration that dual-liganded RXR and RARalpha signaling should allow
      efficient targeting of telomerase in differentiation-resistant tumor cells. Such
      a combination therapy might hold promise in clinic to avoid side effects of ATRA
      whose administration can indiscriminately activate all RARs. Given the tissue
      specific expression of RARs, a tissue-selective therapy targeting telomerase in
      tumor cells by synthetic agonists can be envisioned.

PMID- 14668797
TI  - Characterization and functional analysis of the p42Ets-1 variant of the mouse Ets
      1 transcription factor.
AB  - We have identified the mouse exon VII splice variant of the Ets-1 transcription
      factor. The variant is expressed in all cell lines which express ets-1, at lower
      levels, it is also expressed in the mouse embryo in vivo. The corresponding
      protein, p42Ets-1, is a transcription factor as it is able to bind to specific
      DNA sequences and to transactivate a bona fide ETS reporter vector. A comparison
      of optimal DNA-binding sites shows that p42Ets-1 binds to more various DNA
      sequences than p51Ets-1; p42Ets-1 recognizes the same optimal consensus sequence
      as p51Ets-1, but also many variations of it, mainly at base -1, which is located
      just prior to the GGAA/T core sequence. The binding differences were quantified
      by surface plasmon resonance analyses and the protein region responsible for the
      differences in DNA sequence recognition located in the Val280-Glu302 fragment,
      which is encoded by exon VII. The specific DNA-binding properties of each isoform
      translates into clear differences in activity, p42Ets-1 transactivates the
      natural VE-cadherin gene promoter through both ETS-binding site (EBS)2 and EBS4
      whereas p51Ets-1 is mainly active on EBS4. Altogether, our data suggest that
      p42Ets-1 acts as a distinct transcription factor from p51Ets-1.

PMID- 14668796
TI  - Epidermal growth factor receptor-dependent activation of Gab1 is involved in ErbB
      2-mediated mammary tumor progression.
AB  - Activation of the epidermal growth factor receptor (EGFR) family is thought to
      play an important role in mammary tumorigenesis and metastasis. The potent
      transforming activity of the EGFR family is due to their ability to
      heterodimerize with each other in response to a number of mitogenic ligands. The
      formation of EGFR and ErbB-2 heterodimers has been recently implicated as an
      important factor in the induction of sporadic human breast cancers. To directly
      assess whether the catalytic activity of EGFR is required for ErbB-2 induction of
      mammary tumors, we have interbred transgenic mice expressing ErbB-2 oncogene
      under the transcriptional control of the mouse mammary tumor virus (MMTV)
      promoter/enhancer to a naturally occurring mouse mutant carrying a catalytically
      impaired EGFR (waved-2 mice). Although the female transgenic mice possessing
      mutant EGFR developed mammary tumors, the tumors occurred only after a delayed
      latency period, and were fewer in number. The impaired tumor phenotype was
      further correlated with debilitated phosphorylation of the Gab1 multisubstrate
      adapter. These observations provide evidence that efficient ErbB-2-induced
      mammary tumor progression requires EGFR-dependent activation of Gab1.

PMID- 14668798
TI  - Stability of the Peutz-Jeghers syndrome kinase LKB1 requires its binding to the
      molecular chaperones Hsp90/Cdc37.
AB  - Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by
      the presence of multiple gastrointestinal polyps and an increased risk for
      various types of cancers. Inactivating germline mutations of the LKB1 gene, which
      encodes a serine/threonine kinase, are responsible for the majority of PJS cases.
      Here, we show that the heteromeric complex containing the molecular chaperones
      Hsp90 and Cdc37/p50 interacts with the kinase domain of LKB1. Treatment of cells
      with either geldanamycin or novobiocin, two pharmacological inhibitors of Hsp90
      causes the destabilization of LKB1. Furthermore, geldanamycin treatment leads to
      the ubiquitination and the rapid degradation of LKB1 by the proteasome-dependent
      pathway. In addition, we found that a LKB1 point mutation identified in a
      sporadic testicular cancer, weakens the interaction of LKB1 with both Hsp90 and
      Cdc37/p50 and enhances its sensitivity to the destabilizing effect of
      geldanamycin. Collectively, our results demonstrate that the Hsp90/Cdc37 complex
      is a major regulator of the stability of the LKB1 tumor suppressor. Furthermore,
      these data draw attention to the possible adverse consequences of antitumor drugs
      that target Hsp90, such as antibiotics related to geldanamycin, which could
      disrupt LKB1 function and promote the development of polyps and carcinomatous
      lesions.

PMID- 14668799
TI  - Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation.
AB  - The transcription factor GATA-1 plays a significant role in erythroid
      differentiation and association with CBP stimulates its activity by acetylation.
      It is possible that histone deacetylases (HDACs) repress the activity of GATA-1.
      In the present study, we investigated whether class I and class II HDACs interact
      with GATA-1 to regulate its function and indeed, GATA-1 is directly associated
      with HDAC3, HDAC4 and HDAC5. The expression profiling and our previous
      observation that GATA-2 interacts with members of the HDAC family prompted us to
      investigate further the biological relevance of the interaction between GATA-1
      and HDAC5. Coexpression of HDAC5 suppressed the transcriptional potential of GATA
      1. Our results demonstrated that GATA-1 and HDAC5 colocalized to the nucleus of
      murine erythroleukemia (MEL) cells. Furthermore, a portion of HDAC5 moved to the
      cytoplasm concomitant with MEL cell erythroid differentiation, which was induced
      by treatment with N,N'-hexamethylenebisacetamide. These observations support the
      suggestion that control of the HDAC5 nucleocytoplasmic distribution might be
      associated with MEL cell differentiation, possibly through regulated GATA-1
      transactivation.

PMID- 14668800
TI  - Chimaerism and erythroid marker expression after microinjection of human acute
      myeloid leukaemia cells into murine blastocysts.
AB  - It has been suggested that the embryonic microenvironment can control the
      survival and the transformed phenotype of tumour cells. Here, we addressed the
      hypothesis that the murine embryonic microenvironment can induce the
      differentiation of human tumour cells. To examine such interactions, we injected
      human leukaemic cells into preimplantation murine blastocysts at embryonic day
      3.5 of gestation (E3.5). Microinjection of human KG-1 myeloid leukaemia cells and
      primary human acute myeloid leukaemia (AML) cells led to the generation of
      chimaeric embryos and adults. We observed that in E12.5 murine embryos, KG-1
      cells were preferentially detected in yolk sac and peripheral blood, while
      primary AML cells mainly seeded the aorta gonad mesonephros region of chimaeric
      embryos. Analysis of the donor contribution in 15 different adult tissues showed
      that progeny of primary AML cells seeded to various haematopoietic and
      nonhaematopoietic tissues. Chimaeric embryos and adults showed no apparent tumour
      formation. Furthermore, analysis of chimaeric E12.5 embryos revealed that the
      progeny of human KG-1 cells activated erythroid-specific human globin and
      glycophorin A expression. In summary, our data indicate that human AML cells
      activate markers of erythroid differentiation after injection into early murine
      embryos.

PMID- 14668801
TI  - BRAF mutations characterize colon but not gastric cancer with mismatch repair
      deficiency.
AB  - Genes from the RAF family are Ras-regulated kinases involved in growth cellular
      responses. Recently, a V599E hotspot mutation within the BRAF gene was reported
      in a high percentage of colorectal tumors and significantly associated to
      defective mismatch repair (MMR). Additionally, BRAF mutations were described only
      in K-Ras-negative colon carcinomas, suggesting that BRAF/K-Ras activating
      mutations might be alternative genetic events in colon cancer. We have addressed
      to what extent the tumorigenic-positive selection exerted by BRAF mutations seen
      in colorectal MMR-deficient tumors was also involved in the tumorigenesis of
      gastric cancer. Accordingly, BRAF mutations were detected in 34% (25/74) of
      colorectal MMR-deficient tumors and in 5% (7/142) of MMR-proficient colorectal
      cases (P=0.0001). All mutations found in the MSI cases corresponded to the
      previously reported hotspot V599E. Two D593K and a K600E additional mutations
      were also detected in three MSS cases. However, only one mutation of BRAF was
      found within 124 MSS gastric tumors and none in 37 MSI gastric tumors, clearly
      suggesting that BRAF mutations are not involved in gastric tumorigenesis.
      Nonetheless, a high incidence of mutations of K-Ras was found within the MSI
      gastric group of tumors (P=0.0005), suggesting that the activation of K-Ras
      dependent pathways contributes to the tumorigenesis of gastric cancers with MMR
      deficiency. Accordingly, our results show evidences that BRAF mutations
      characterize colon but not gastric tumors with MMR deficiency and are not
      involved in the tumorigenesis of gastric cancer of the mutator phenotype pathway.

PMID- 14668802
TI  - Cell migration and the control of post-natal T-cell lymphopoiesis in the thymus.

PMID- 14668803
TI  - Homing and cellular traffic in lymph nodes.

PMID- 14668804
TI  - Ocular immune privilege: therapeutic opportunities from an experiment of nature.

PMID- 14668805
TI  - Regulating antigen-receptor gene assembly.

PMID- 14668806
TI  - Regulation of JAK-STAT signalling in the immune system.

PMID- 14668807
TI  - Therapeutic angiogenesis in cardiovascular disease.

PMID- 14668808
TI  - Targeting the Nogo receptor to treat central nervous system injuries.

PMID- 14668809
TI  - COX-2 and beyond: Approaches to prostaglandin inhibition in human disease.

PMID- 14668810
TI  - Ace revisited: a new target for structure-based drug design.

PMID- 14668811
TI  - New targets for allergic rhinitis--a disease of civilization.

PMID- 14668812
TI  - Virtual drug discovery and development for neglected diseases through public
      private partnerships.

PMID- 14668813
TI  - Aromatase inhibitors for breast cancer: lessons from the laboratory.

PMID- 14668814
TI  - Stem cells and breast cancer: A field in transit.

PMID- 14668815
TI  - Unconventional therapy for prostate cancer: good, bad or questionable?

PMID- 14668816
TI  - AP-1: a double-edged sword in tumorigenesis.

PMID- 14668817
TI  - Analysing differential gene expression in cancer.

PMID- 14668818
TI  - Merlin and ERM proteins: unappreciated roles in cancer development?

PMID- 14668819
TI  - Derivation of embryonic germ cells and male gametes from embryonic stem cells.
AB  - Egg and sperm cells (gametes) of the mouse are derived from a founder population
      of primordial germ cells that are set aside early in embryogenesis. Primordial
      germ cells arise from the proximal epiblast, a region of the early mouse embryo
      that also contributes to the first blood lineages of the embryonic yolk sac.
      Embryonic stem cells differentiate in vitro into cystic structures called
      embryoid bodies consisting of tissue lineages typical of the early mouse embryo.
      Because embryoid bodies sustain blood development, we reasoned that they might
      also support primordial germ cell formation. Here we isolate primordial germ
      cells from embryoid bodies, and derive continuously growing lines of embryonic
      germ cells. Embryonic germ cells show erasure of the methylation markers
      (imprints) of the Igf2r and H19 genes, a property characteristic of the germ
      lineage. We show that embryoid bodies support maturation of the primordial germ
      cells into haploid male gametes, which when injected into oocytes restore the
      somatic diploid chromosome complement and develop into blastocysts. Our ability
      to derive germ cells from embryonic stem cells provides an accessible in vitro
      model system for studies of germline epigenetic modification and mammalian
      gametogenesis.

PMID- 14668820
TI  - Lunar dreams, again.

PMID- 14668821
TI  - A new home for molecular biologists.

PMID- 14668822
TI  - Berkeley accused of biotech bias as ecologist is denied tenure.

PMID- 14668823
TI  - Ecologists attack endangered-species logjam.

PMID- 14668824
TI  - Swamp row bogs down Singapore's bid to reclaim land.

PMID- 14668825
TI  - Plague trial verdict leaves biologists split on biodefence.

PMID- 14668826
TI  - National Science Foundation facing budget let-down.

PMID- 14668827
TI  - Mystery remains as journal withdraws paper.

PMID- 14668828
TI  - Maths institute planned to meet multiplying demand.

PMID- 14668829
TI  - Sheep horns downsized by hunters' taste for trophies.

PMID- 14668830
TI  - Europe dithers over regulations for stem-cell research.

PMID- 14668833
TI  - QUAD system offers fair shares to all authors.

PMID- 14668832
TI  - Boom, or bust?

PMID- 14668834
TI  - Tidewater glaciers move at their own pace.

PMID- 14668839
TI  - Basic concepts: to put it simply...

PMID- 14668841
TI  - Quantum optics: light at a standstill.

PMID- 14668840
TI  - Virus evolution: epidemics-in-waiting.

PMID- 14668842
TI  - Chemistry: cellulose stacks up.

PMID- 14668843
TI  - Geomorphology: nature, nurture and landscape.

PMID- 14668845
TI  - Signal transduction: molecular monogamy.

PMID- 14668846
TI  - Chirality: organic films with a twist.

PMID- 14668847
TI  - Obituary: Bertram N. Brockhouse (1918-2003).

PMID- 14668849
TI  - Geomorphology: solitary wave behaviour of sand dunes.

PMID- 14668850
TI  - Genetics: influence of TOR kinase on lifespan in C. elegans.

PMID- 14668851
TI  - Metabolism: ecology shapes bird bioenergetics.

PMID- 14668852
TI  - Geochronology: dating of the Herto hominin fossils.

PMID- 14668854
TI  - Centre-surround inhibition among olfactory bulb glomeruli.
AB  - Centre-surround inhibition--the suppression of activity of neighbouring cells by
      a central group of neurons--is a fundamental mechanism that increases contrast in
      patterned sensory processing. The initial stage of neural processing in olfaction
      occurs in olfactory bulb glomeruli, but evidence for functional interactions
      between glomeruli is fragmentary. Here we show that the so-called 'short axon'
      cells, contrary to their name, send interglomerular axons over long distances to
      form excitatory synapses with inhibitory periglomerular neurons up to 20-30
      glomeruli away. Interglomerular excitation of these periglomerular cells potently
      inhibits mitral cells and forms an on-centre, off-surround circuit. This
      interglomerular centre-surround inhibitory network, along with the well
      established mitral-granule-mitral inhibitory circuit, forms a serial, two-stage
      inhibitory circuit that could enhance spatiotemporal responses to odours.

PMID- 14668855
TI  - Crystal structure of plant photosystem I.
AB  - Oxygenic photosynthesis is the principal producer of both oxygen and organic
      matter on Earth. The conversion of sunlight into chemical energy is driven by two
      multisubunit membrane protein complexes named photosystem I and II. We determined
      the crystal structure of the complete photosystem I (PSI) from a higher plant
      (Pisum sativum var. alaska) to 4.4 A resolution. Its intricate structure shows 12
      core subunits, 4 different light-harvesting membrane proteins (LHCI) assembled in
      a half-moon shape on one side of the core, 45 transmembrane helices, 167
      chlorophylls, 3 Fe-S clusters and 2 phylloquinones. About 20 chlorophylls are
      positioned in strategic locations in the cleft between LHCI and the core. This
      structure provides a framework for exploration not only of energy and electron
      transfer but also of the evolutionary forces that shaped the photosynthetic
      apparatus of terrestrial plants after the divergence of chloroplasts from marine
      cyanobacteria one billion years ago.

PMID- 14668856
TI  - The essential signature of a massive starburst in a distant quasar.
AB  - Observations of carbon monoxide emission in high-redshift (zeta > 2) galaxies
      indicate the presence of large amounts of molecular gas. Many of these galaxies
      contain an active galactic nucleus powered by accretion of gas onto a
      supermassive black hole, and a key question is whether their extremely high
      infrared luminosities result from the active galactic nucleus, from bursts of
      massive star formation (associated with the molecular gas), or both. In the Milky
      Way, high-mass stars form in the dense cores of interstellar molecular clouds,
      where gas densities are n(H2) > 10(5) cm(-3) (refs 1, 2). Recent surveys show
      that virtually all galactic sites of high-mass star formation have similarly high
      densities. The bulk of the cloud material traced by CO observations, however, is
      at a much lower density. For galaxies in the local Universe, the HCN molecule is
      an effective tracer of high-density molecular gas. Here we report observations of
      HCN emission from the infrared-luminous 'Cloverleaf' quasar (at a redshift zeta =
      2.5579). The HCN line luminosity indicates the presence of 10 billion solar
      masses of very dense gas, an essential feature of an immense starburst, which
      contributes, together with the active galactic nucleus it harbours, to its high
      infrared luminosity.

PMID- 14668857
TI  - Stationary pulses of light in an atomic medium.
AB  - Physical processes that could facilitate coherent control of light propagation
      are under active exploration. In addition to their fundamental interest, these
      efforts are stimulated by practical possibilities, such as the development of a
      quantum memory for photonic states. Controlled localization and storage of
      photonic pulses may also allow novel approaches to manipulating of light via
      enhanced nonlinear optical processes. Recently, electromagnetically induced
      transparency was used to reduce the group velocity of propagating light pulses
      and to reversibly map propagating light pulses into stationary spin excitations
      in atomic media. Here we describe and experimentally demonstrate a technique in
      which light propagating in a medium of Rb atoms is converted into an excitation
      with localized, stationary electromagnetic energy, which can be held and released
      after a controllable interval. Our method creates pulses of light with stationary
      envelopes bound to an atomic spin coherence, offering new possibilities for
      photon state manipulation and nonlinear optical processes at low light levels.

PMID- 14668858
TI  - An off-normal fibre-like texture in thin films on single-crystal substrates.
AB  - In the context of materials science, texture describes the statistical
      distribution of grain orientations. It is an important characteristic of the
      microstructure of polycrystalline films, determining various electrical, magnetic
      and mechanical properties. Three types of texture component are usually
      distinguished in thin films: random texture, when grains have no preferred
      orientation; fibre texture, for which one crystallographic axis of the film is
      parallel to the substrate normal, while there is a rotational degree of freedom
      around the fibre axis; and epitaxial alignment (or in-plane texture) on single
      crystal substrates, where an in-plane alignment fixes all three axes of the grain
      with respect to the substrate. Here we report a fourth type of texture--which we
      call axiotaxy--identified from complex but symmetrical patterns of lines on
      diffraction pole figures for thin films formed by solid-state reactions. The
      texture is characterized by the alignment of planes in the film and substrate
      that share the same d-spacing. This preferred alignment of planes across the
      interface manifests itself as a fibre texture lying off-normal to the sample
      surface, with the fibre axis perpendicular to certain planes in the substrate.
      This texture forms because it results in an interface, which is periodic in one
      dimension, preserved independently of interfacial curvature. This new type of
      preferred orientation may be the dominant type of texture for a wide class of
      materials and crystal structures.

PMID- 14668859
TI  - Coupled spatial variations in precipitation and long-term erosion rates across
      the Washington Cascades.
AB  - Past studies of tectonically active mountain ranges have suggested strong
      coupling and feedbacks between climate, tectonics and topography. For example,
      rock uplift generates topographic relief, thereby enhancing precipitation, which
      focuses erosion and in turn influences rates and spatial patterns of further rock
      uplift. Although theoretical links between climate, erosion and uplift have
      received much attention, few studies have shown convincing correlations between
      observable indices of these processes on mountain-range scales. Here we show that
      strongly varying long-term (>10(6)-10(7) yr) erosion rates inferred from apatite
      (U-Th)/He cooling ages across the Cascades mountains of Washington state closely
      track modern mean annual precipitation rates. Erosion and precipitation rates
      vary over an order of magnitude across the range with maxima of 0.33 mm yr(-1)
      and 3.5 m yr(-1), respectively, with both maxima located 50 km west (windward) of
      the topographic crest of the range. These data demonstrate a strong coupling
      between precipitation and long-term erosion rates on the mountain-range scale. If
      the range is currently in topographic steady state, rock uplift on the west flank
      is three to ten times faster than elsewhere in the range, possibly in response to
      climatically focused erosion.

PMID- 14668860
TI  - Links between erosion, runoff variability and seismicity in the Taiwan orogen.
AB  - The erosion of mountain belts controls their topographic and structural evolution
      and is the main source of sediment delivered to the oceans. Mountain erosion
      rates have been estimated from current relief and precipitation, but a more
      complete evaluation of the controls on erosion rates requires detailed
      measurements across a range of timescales. Here we report erosion rates in the
      Taiwan mountains estimated from modern river sediment loads, Holocene river
      incision and thermochronometry on a million-year scale. Estimated erosion rates
      within the actively deforming mountains are high (3-6 mm yr(-1)) on all
      timescales, but the pattern of erosion has changed over time in response to the
      migration of localized tectonic deformation. Modern, decadal-scale erosion rates
      correlate with historical seismicity and storm-driven runoff variability. The
      highest erosion rates are found where rapid deformation, high storm frequency and
      weak substrates coincide, despite low topographic relief.

PMID- 14668861
TI  - Decoupling of erosion and precipitation in the Himalayas.
AB  - The hypothesis that abrupt spatial gradients in erosion can cause high strain
      rates in active orogens has been supported by numerical models that couple
      erosional processes with lithospheric deformation via gravitational feedbacks.
      Most such models invoke a 'stream-power' rule, in which either increased
      discharge or steeper channel slopes cause higher erosion rates. Spatial
      variations in precipitation and slopes are therefore predicted to correlate with
      gradients in both erosion rates and crustal strain. Here we combine observations
      from a meteorological network across the Greater Himalaya, Nepal, along with
      estimates of erosion rates at geologic timescales (greater than 100,000 yr) from
      low-temperature thermochronometry. Across a zone of about 20 km length spanning
      the Himalayan crest and encompassing a more than fivefold difference in monsoon
      precipitation, significant spatial variations in geologic erosion rates are not
      detectable. Decreased rainfall is not balanced by steeper channels. Instead,
      additional factors that influence river incision rates, such as channel width and
      sediment concentrations, must compensate for decreasing precipitation. Overall,
      spatially constant erosion is a response to uniform, upward tectonic transport of
      Greater Himalayan rock above a crustal ramp.

PMID- 14668862
TI  - Undesirable evolutionary consequences of trophy hunting.
AB  - Phenotype-based selective harvests, including trophy hunting, can have important
      implications for sustainable wildlife management if they target heritable traits.
      Here we show that in an evolutionary response to sport hunting of bighorn trophy
      rams (Ovis canadensis) body weight and horn size have declined significantly over
      time. We used quantitative genetic analyses, based on a partly genetically
      reconstructed pedigree from a 30-year study of a wild population in which trophy
      hunting targeted rams with rapidly growing horns, to explore the evolutionary
      response to hunter selection on ram weight and horn size. Both traits were highly
      heritable, and trophy-harvested rams were of significantly higher genetic
      'breeding value' for weight and horn size than rams that were not harvested. Rams
      of high breeding value were also shot at an early age, and thus did not achieve
      high reproductive success. Declines in mean breeding values for weight and horn
      size therefore occurred in response to unrestricted trophy hunting, resulting in
      the production of smaller-horned, lighter rams, and fewer trophies.

PMID- 14668863
TI  - The role of evolution in the emergence of infectious diseases.
AB  - It is unclear when, where and how novel pathogens such as human immunodeficiency
      virus (HIV), monkeypox and severe acute respiratory syndrome (SARS) will cross
      the barriers that separate their natural reservoirs from human populations and
      ignite the epidemic spread of novel infectious diseases. New pathogens are
      believed to emerge from animal reservoirs when ecological changes increase the
      pathogen's opportunities to enter the human population and to generate subsequent
      human-to-human transmission. Effective human-to-human transmission requires that
      the pathogen's basic reproductive number, R(0), should exceed one, where R(0) is
      the average number of secondary infections arising from one infected individual
      in a completely susceptible population. However, an increase in R(0), even when
      insufficient to generate an epidemic, nonetheless increases the number of
      subsequently infected individuals. Here we show that, as a consequence of this,
      the probability of pathogen evolution to R(0) > 1 and subsequent disease
      emergence can increase markedly.

PMID- 14668864
TI  - Plankton effect on cod recruitment in the North Sea.
AB  - The Atlantic cod (Gadus morhua L.) has been overexploited in the North Sea since
      the late 1960s and great concern has been expressed about the decline in cod
      biomass and recruitment. Here we show that, in addition to the effects of
      overfishing, fluctuations in plankton have resulted in long-term changes in cod
      recruitment in the North Sea (bottom-up control). Survival of larval cod is shown
      to depend on three key biological parameters of their prey: the mean size of
      prey, seasonal timing and abundance. We suggest a mechanism, involving the
      match/mismatch hypothesis, by which variability in temperature affects larval cod
      survival and conclude that rising temperature since the mid-1980s has modified
      the plankton ecosystem in a way that reduces the survival of young cod.

PMID- 14668865
TI  - Visual control of action but not perception requires analytical processing of
      object shape.
AB  - The visual perception of object shape depends on 'holistic' processing in which a
      given dimension cannot be perceptually isolated from the other dimensions of the
      object. The visual control of action (such as grasping an object), however, which
      is mediated by cortical areas that are largely independent of those mediating
      conscious perception, must take into account only the most action-relevant
      dimension of an object without being misled by other non-relevant object
      features. Here we report the results of two experiments showing that vision for
      perception and vision for action deal with objects in a fundamentally different
      manner. We tested participants' ability to make perceptual judgements of the
      width of different rectangular objects or to grasp them across their width, while
      in both cases ignoring length. Participants could not ignore length when making
      perceptual judgements of width but they could completely ignore length when
      grasping the same objects. These results suggest that in situations in which the
      elementary dimensions of an object's shape are perceived in a holistic manner,
      the same dimensions are treated analytically when a visually guided action is
      directed at that same object.

PMID- 14668866
TI  - Parallel colour-opponent pathways to primary visual cortex.
AB  - The trichromatic primate retina parses the colour content of a visual scene into
      'red/green' and 'blue/yellow' representations. Cortical circuits must combine the
      information encoded in these colour-opponent signals to reconstruct the full
      range of perceived colours. Red/green and blue/yellow inputs are relayed by the
      lateral geniculate nucleus (LGN) of thalamus to primary visual cortex (V1), so
      understanding how cortical circuits transform these signals requires
      understanding how LGN inputs to V1 are organized. Here we report direct
      recordings from LGN afferent axons in muscimol-inactivated V1. We found that
      blue/yellow afferents terminated exclusively in superficial cortical layers 3B
      and 4A, whereas red/green afferents were encountered only in deeper cortex, in
      lower layer 4C. We also describe a distinct cortical target for 'blue-OFF' cells,
      whose afferents terminated in layer 4A and seemed patchy in organization. The
      more common 'blue-ON' afferents were found in 4A as well as lower layer 2/3.
      Chromatic information is thus conveyed to V1 by parallel, anatomically segregated
      colour-opponent systems, to be combined at a later stage of the colour circuit.

PMID- 14668867
TI  - Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1.
AB  - Regulated apoptosis is essential for both the development and the subsequent
      maintenance of the immune system. Interleukins, including IL-2, IL-4, IL-7 and IL
      15, heavily influence lymphocyte survival during the vulnerable stages of VDJ
      rearrangement and later in ensuring cellular homeostasis, but the genes
      specifically responsible for the development and maintenance of lymphocytes have
      not been identified. The antiapoptotic protein MCL-1 is an attractive candidate,
      as it is highly regulated, appears to enhance short-term survival and functions
      at an apical step in genotoxic deaths. However, Mcl-1 deficiency results in peri
      implantation lethality. Here we show that mice conditional for Mcl-1 display a
      profound reduction in B and T lymphocytes when MCL-1 is removed. Deletion of Mcl
      1 during early lymphocyte differentiation increased apoptosis and arrested the
      development at pro-B-cell and double-negative T-cell stages. Induced deletion of
      Mcl-1 in peripheral B- and T-cell populations resulted in their rapid loss.
      Moreover, IL-7 both induced and required MCL-1 to mediate lymphocyte survival.
      Thus, MCL-1, which selectively inhibits the proapoptotic protein BIM, is
      essential both early in lymphoid development and later on in the maintenance of
      mature lymphocytes.

PMID- 14668868
TI  - Optimization of specificity in a cellular protein interaction network by negative
      selection.
AB  - Most proteins that participate in cellular signalling networks contain modular
      protein-interaction domains. Multiple versions of such domains are present within
      a given organism: the yeast proteome, for example, contains 27 different Src
      homology 3 (SH3) domains. This raises the potential problem of cross-reaction. It
      is generally thought that isolated domain-ligand pairs lack sufficient
      information to encode biologically unique interactions, and that specificity is
      instead encoded by the context in which the interaction pairs are presented. Here
      we show that an isolated peptide ligand from the yeast protein Pbs2 recognizes
      its biological partner, the SH3 domain from Sho1, with near-absolute specificity-
      no other SH3 domain present in the yeast genome cross-reacts with the Pbs2
      peptide, in vivo or in vitro. Such high specificity, however, is not observed in
      a set of non-yeast SH3 domains, and Pbs2 motif variants that cross-react with
      other SH3 domains confer a fitness defect, indicating that the Pbs2 motif might
      have been optimized to minimize interaction with competing domains specifically
      found in yeast. System-wide negative selection is a subtle but powerful
      evolutionary mechanism to optimize specificity within an interaction network
      composed of overlapping recognition elements.

PMID- 14668869
TI  - Gating of the rapid shade-avoidance response by the circadian clock in plants.
AB  - The phytochromes are a family of plant photoreceptor proteins that control
      several adaptive developmental strategies. For example, the phytochromes perceive
      far-red light (wavelengths between 700 and 800 nm) reflected or scattered from
      the leaves of nearby vegetation. This provides an early warning of potential
      shading, and triggers a series of 'shade-avoidance' responses, such as a rapid
      increase in elongation, by which the plant attempts to overgrow its neighbours.
      Other, less immediate, responses include accelerated flowering and early
      production of seeds. However, little is known about the molecular events that
      connect light perception with increased growth in shade avoidance. Here we show
      that the circadian clock gates this rapid shade-avoidance response. It is most
      apparent around dusk and is accompanied by altered expression of several genes.
      One of these rapidly responsive genes encodes a basic helix-loop-helix protein,
      PIL1, previously shown to interact with the clock protein TOC1 (ref. 4).
      Furthermore PIL1 and TOC1 are both required for the accelerated growth associated
      with the shade-avoidance response.

PMID- 14668871
TI  - San Diego.

PMID- 14668872
TI  - Good neighbours.

PMID- 14668873
TI  - The view from the top.

PMID- 14668874
TI  - Genesis of a high-tech hub.

PMID- 14668875
TI  - Best of both worlds.

PMID- 14668876
TI  - Turning technology into gold.

PMID- 14668877
TI  - Tomorrow's world.

PMID- 14668878
TI  - Different directions?

PMID- 14668879
TI  - In search of the elite.

PMID- 14668880
TI  - High-tech, high society.

PMID- 14668881
TI  - To affinity and beyond.

PMID- 14668882
TI  - Playing with the pieces.

PMID- 14668883
TI  - Going into production.

PMID- 14668884
TI  - Antibodies where you want them.

PMID- 14668886
TI  - Forcing the market.

PMID- 14668887
TI  - A developing theme for AIDS.

PMID- 14668888
TI  - Gene therapy of coronary artery disease with phvegf165--early outcome.
AB  - BACKGROUND: Gene therapy is a new, experimental method of treatment in patients
      with coronary artery disease (CAD). AIM: To determine the safety and efficacy of
      gene encoding vascular endothelial growth factor (VEGF165) administered directly
      into the myocardium as the single treatment or combined with coronary artery by
      pass grafting (CABG). METHODS: VEGF gene transfer was performed in 22 patients
      (20 male, 2 female, ages from 48 to 73 years old). A 200 micro g of the plasmid
      encoding VEGF165 was injected into the ischaemic myocardium which could not be
      surgically revascularised in patients undergoing CABG (n=14), and 400 micro g -
      in patients without CABG (n=8). The value of ejection fraction (EF), myocardial
      perfusion, angiogram, ventriculography, and nitroglycerine consumption as well as
      quality of life were evaluated pre- and postoperatively. RESULTS: The majority of
      patients had no complications and no fatal outcome was observed. Two patients
      developed acute myocardial infarction. Left ventricular function values improved
      and the majority of patients were free from angina 6 months after surgery.
      Patients reported improved quality of life and a reduction in nitroglycerine
      usage. A reduction in the ischaemic defects detected by SPECT was also observed.
      In some patients angiography revealed improved collateral filling. CONCLUSIONS:
      Direct myocardial administration of genes encoding VEGF165 can be an effective
      method of treatment in patients with chronic and advanced CAD either as a
      supplementary treatment or as a single therapy.

PMID- 14668889
TI  - Cardiological syndrome X. Non-invasive assessment of endothelial function and
      arterial compliance.
AB  - BACKGROUND: Mechanisms responsible for cardiological syndrome X are complex and
      not well understood. It has been postulated that impaired endothelial function
      and abnormal reactivity of coronary vessels may play a role in the pathogenesis
      of this condition. AIM: To assess mechanical properties of peripheral arterial
      vessels and both endothelium-dependent and endothelium-independent vessel
      reactivity in patients with or without atherosclerotic lesions in coronary
      arteries. METHODS: The study group consisted of 100 patients with typical angina
      and positive exercise test who underwent coronary angiography. Based on
      angiographic results, the patients were divided into two groups: 50 patients with
      normal coronary angiograms and 50 age- and gender-matched patients with at least
      one significant coronary artery lesion (coronary artery disease (CAD) group). The
      control group consisted of 40 healthy volunteers without risk factors of
      atherosclerosis. The compliance of arterial vessels was assessed by automatic
      measurement of pulse wave velocity (PWV). Endothelial function was examined by
      ultrasonographic measurement of the diameter of brachial artery following passive
      hyperaemia (endothelium-dependent vessel distension) and following nitroglycerine
      (endothelium-independent mechanism). RESULTS: Among all three studied groups, the
      PWV values were the highest in patients with CAD. Patients with syndrome X had
      significantly higher PWV than in controls. A cut-off PWV value of 10.5 m/s
      distinguished patients with syndrome X from those with CAD. Endothelium-dependent
      arterial distensibility was significantly lower in patients with syndrome X than
      in controls; the lowest values were observed in patients with CAD. Among patients
      with syndrome X, the endothelium-dependent arterial vessel distensibility was the
      only parameter significantly influencing PWV results. CONCLUSIONS: PWV was
      significantly increased in patients with syndrome X which suggests a decreased
      arterial vessel compliance. These results and the impairment of endothelium
      dependent relaxation suggest a similar pathomechanism of altered arterial
      reactivity in patients with syndrome X and in patients with CAD.

PMID- 14668890
TI  - Serial echocardiographic assessment of the left ventricular function after direct
      PCI.
AB  - BACKGROUND: Acute myocardial infarction (AMI) causes remodelling of the left
      ventricle (LV). Restoration of patency of an infarct-related artery by
      percutaneous coronary interventions (PCI) may prevent or inhibit cardiac
      remodelling. AIM: To assess LV contractility and function by serial
      echocardiographic examinations. METHODS: The study group consisted of 61 patients
      (47 males, mean age 60+/-10 years) with acute MI treated with direct PCI.
      Echocardiography was performed 6-8 days after PCI, and 1, 6 and 12 months
      thereafter. RESULTS: LV ejection fraction increased significantly at the end of
      the first month in comparison with the baseline examination whereas EF values
      obtained after 6 months and after 1 year were not significantly different. Wall
      motion score index showed a significant improvement after one month, whereas it
      did not show any further improvement when measured after 6 or 12 months after
      AMI. The baseline LV end-diastolic diameter was 49+/-6 mm and did not change
      after one or 6 months, whereas it increased significantly 12 months after AMI.
      The baseline LV end-systolic diameter was 37+/-5 mm. At the one-month and six
      month examinations it was similar to the baseline values but increased
      significantly to 38+/-6 mm after one year. CONCLUSIONS: These results confirm the
      beneficial effects of PCI-induced infarct-related artery patency on LV
      remodelling after AMI.

PMID- 14668891
TI  - Acute coronary syndrome: potassium, magnesium and cardiac arrhythmia.
AB  - BACKGROUND: Cardiac arrhythmia is often present in patients with acute coronary
      syndrome (ACS) and may be due to the electrolyte imbalance. AIM: To assess the
      prevalence and clinical significance of electrolyte imbalance in ACS. METHODS:
      Serum potassium and magnesium levels were measured within the first few hours in
      204 consecutive patients with ACS admitted to our department over a period of 23
      months. Cardiac arrhythmia was documented using continuous ECG monitoring,
      telemetry or standard ECG. RESULTS: Hypokalemia was observed in 34% of patients,
      and was significantly associated with the occurrence of life-threatening
      ventricular arrhythmias (26% of patients with potassium level <4 mmol/l vs 11.9%
      of patients with normokalemia, p<0.001). No relationship was found between
      potassium level and supraventricular arrhythmias or in-hospital mortality.
      Decreased magnesium serum concentration was found in 22% of patients but was not
      significantly associated with cardiac arrhythmias or mortality. CONCLUSIONS:
      Hypokalemia and hypomagnesemia are often present in patients with ACS. The former
      is associated with dangerous ventricular arrhythmias. Early assessment of
      electrolyte serum concentration is needed in order to implement proper
      supplementation.

PMID- 14668892
TI  - Subacute stent thrombosis following coronary angioplasty: incidence and risk
      factors.
AB  - BACKGROUND: Subacute stent thrombosis was a significant complication in the early
      years of coronary stenting, often leading to myocardial infarction, need for
      urgent surgery or even death. The introduction of intracoronary ultrasound
      enabled the identification and proper treatment of the main causes of stent
      thrombosis, reducing the rate of this complication to 1%. AIM: To identify risk
      factors of subacute stent thrombosis. METHODS: Data concerning 845 procedures
      with a single stent implantation in patients with stable or unstable angina,
      undergoing this procedure between 1998 and 2000, were analysed. RESULTS: Subacute
      stent thrombosis occurred in 13 (1.54%) patients. Risk factors for this
      complication included urgent procedures (so-called bailout stenting), improper
      pre-treatment with drugs ("ad hoc" procedures), dissection uncovered by stent,
      and poor final result of procedure (higher degree of residual stenosis). The
      majority of these patients developed myocardial infarction in spite of the fact
      that the patency of stented vessel was quickly achieved in all but one patient.
      CONCLUSIONS: Urgent stenting, improper drug pre-treatment and suboptimal result
      of the procedure are the risk factors of subacute stent thrombosis.

PMID- 14668893
TI  - [Myocardial infarction in a patient with hemophilia A--a case report].
AB  - A 43-year-old men with hemophilia A was admitted to CCU due to anginal pain
      lasting for sixteen hours. ECG revealed anterior wall myocardial infarction and
      elevated CK and MB-CK levels confirmed the diagnosis. Exercise test performed
      later was positive and the patient underwent elective coronary angiography which
      showed 90% stenosis of left anterior descending (LAD) and closed circumflex
      coronary artery. Next, angioplasty of LAD, preceded by antihemophilic globulin
      (factor VIII) administration, was successfully performed.

PMID- 14668894
TI  - [Thrombocytopenia and disseminated intravascular coagulation in a patient with
      left atrial myxoma--a case report].
AB  - A case of a 47-year-old man, a Jehovah's Witness, with left atrial myxoma is
      presented. Clinical presentation included several months of thrombocytopenia and
      disseminated intravascular coagulation. Deterioration of heart failure was
      complicated by pneumonia and worsening of disseminated intravascular coagulation.
      Therapeutic challenges related to patient's religious beliefs are discussed.

PMID- 14668895
TI  - [Acute myocardial infarction treated with primary PCI complicated by pulmonary
      embolism--a case report].
AB  - A case of 53-year-old male who was admitted to the hospital due to a chest pain,
      is presented. ECG showed ST elevation in precordial leads. The patient was
      successfully treated with primary angioplasty. On the third day of
      hospitalization, he collapsed with hypotension. Routine echocardiographic
      examination revealed signs of pulmonary embolism. An adequate pharmacotherapy was
      implemented and the patient improved. After 10 days of treatment and
      rehabilitation he was discharged home. The present case report points out on
      pulmonary embolism as a rare but potentially life-threatening complication of
      coronary angioplasty.

PMID- 14668896
TI  - [Pulmonary embolism in a patient with unstable angina treated with surgical
      revascularisation--a case report].
AB  - A case of a 58-year-old female patient with unstable angina is presented. Two
      weeks earlier the patient suffered from acute myocardial infarction treated with
      thrombolysis. The patient underwent surgical revascularisation which was
      complicated by acute pulmonary embolism. Repeated surgery and inspection of
      pulmonary arteries revealed the presence of thrombus which was successfully
      removed. The post-operative course was uneventful. The causes and treatment of
      pulmonary embolism complicating coronary artery by-pass grafting are discussed.

PMID- 14668897
TI  - [Cardiovascular complications of influenza].

PMID- 14668905
TI  - [Infective endocarditis complicated by abscess and perforation of mitral valve--a
      case report].
AB  - A case of a 47-year-old male admitted to our department due to acute myocardial
      infarction, treated effectively with primary angioplasty, is presented. Three
      weeks earlier the patient was admitted to another hospital with a suspicion of
      infective endocarditis. Echocardiography performed in our department after the
      patient recovered from acute phase of MI revealed the presence of mitral valve
      abscess which caused valve perforation. The patient was transferred to another
      institution for cardiac surgery.

PMID- 14668906
TI  - [Electrocardiogram of the month].

PMID- 14668907
TI  - [Angiogram of the month].

PMID- 14668908
TI  - [Pharmacological treatment in patients undergoing coronary angioplasty].

PMID- 14668910
TI  - In vitro and in vivo analyses of the biological activity of RGD peptides towards
      Ab Bomirski melanoma.
AB  - The RGD sequence is present in many extracellular matrix proteins and
      intracellular proteins, including caspases. Synthetic RGD peptides may affect
      adhesion, migration and tumour metastasis, or directly induce apoptosis. Several
      RGD peptides were synthesised, and their anti-adhesive and cytotoxic properties
      were analysed in vitro. The most active peptide (poly RGD) was also tested in
      vivo to assess its modulatory activity on melanoma growth. Synthetic RGD peptides
      inhibit the adhesion of Ab melanoma cells to fibronectin. Poly RGD significantly
      inhibits primary tumour growth. There was no observed cytotoxicity of poly RGD
      towards Ab cells in a medium with 10% serum; however, under the same conditions,
      the anti-adhesive effect of poly RGD was still visible. Experiments on Jurkat
      cells indicated a weak cytotoxicity of poly RGD and a significant cytotoxicity of
      GRGDNP (the reference cytotoxic peptide), retained only under serum-free
      conditions. The anti-tumour effect of poly RGD observed in the Ab Bomirski
      melanoma model is probably due to an anti-adhesive mechanism. The proapoptotic
      activity of RGD peptides is dependent on the absence of serum.

PMID- 14668911
TI  - The interaction of daunorubicin and mitoxantrone with the red blood cells of
      acute myeloid leukemia patients.
AB  - The effect of DNR and MIT on erythrocyte membrane structure was examined using
      Electron Spin Resonance spectroscopy and the fluorimetric technique. The results
      suggest that the in vivo interaction of the drugs with the RBCs of AML patients
      led to a perturbation in the structure of plasma membrane components. Differences
      between DNR and MIT were only noted in the interaction of the drugs with deeper
      regions of the lipid bilayer

PMID- 14668912
TI  - Identification of Phoenix dactylifera L. varieties based on amplified fragment
      length polymorphism (AFLP) markers.
AB  - The amplified fragment length polymorphism (AFLP) technique was applied to
      identify palm varieties. Fluorescence labelled primers were used in selective
      amplifications and the amplified fragments were detected on capillary gel
      electrophoresis using an automated DNA sequencer with the analysis fragment
      option. This is a rapid and efficient technique for detecting a large number of
      DNA markers on the date palm. Phoenix dactylifera L. varieties Bou-Fegous,
      Medjool, and E-528 from Estacion Phoenix (Elche), Spain, were analysed, yielding
      a total of 310 AFLP fragments derived from five primer combinations. The process
      for regenerating the date palm cultivars from in vitro tissue culture should
      yield individuals phenotypically and genetically identical to the explant they
      are derived from. The AFLP markers obtained were successfully used for comparing
      and identifying vitroplants of palm.

PMID- 14668913
TI  - Increased lipogenic potential of rat adipose tissue after repeated dieting--the
      role of SREBP-1 transcription factor.
AB  - Repeated dieting is one of the methods used for weight reduction; however, its
      effectiveness is questionable. We developed an experimental, rat model of
      repeated dieting, which mimics the dietary approach used in the treatment of
      obesity in humans. In this experimental model, despite the lower caloric intake,
      decreased body mass and reduced fat stores, the lipogenic potential of adipose
      tissue increased. We observed a substantial increase in fatty acid synthase (a
      key lipogenic enzyme) gene expression in rat adipose tissue accompanied by a 9
      fold increase in the serum insulin level. Fatty acid synthase gene expression is
      controlled at the transcriptional level by SREBP-1. In this study, a remarkable
      increase (24-fold) in SREBP-1 protein amount, parallel to that in fatty acid
      synthase mRNA level, protein concentration and enzyme activity was observed after
      multiple cycles of fasting-refeeding. Although it is possible that the
      interactions between transcription factors are more complex, we propose that the
      pivotal role in the increase of the lipogenic potential of adipose tissue after
      repeated dieting may be played by SREBP-1.

PMID- 14668914
TI  - Quantitative analysis of LacCer/CDw17 in human myelogenous leukaemic cells.
AB  - LacCer/CDw17 is the most abundant GSL in neutrophils. The cell-surface and
      intracellular presence of LacCer was determined quantitatively using anti-CDw17
      mAbs in a flow cytometry assay. The quantified alterations in the level of CDw17
      antigen expression are consistent with alterations in LacCer content, determined
      chemically. Our results show that CDw17 antigen expression defines successive
      stages in the maturation of the myeloid cell. The assessment of cell-surface and
      intracellular CDw17 expression may be useful in evaluating neutrophil
      physiological status.

PMID- 14668915
TI  - Capsaicin-induced activation of erythrocyte membrane sodium/potassium and calcium
      adenosine triphosphatases.
AB  - Capsaicin is the pungent ingredient present in hot peppers of the genus Capsicum.
      Capsaicin's effect on sensory neurons has been well studied; however, its effect
      on non-neuronal cells is still not fully understood. This study was undertaken to
      evaluate the effect of capsaicin on erythrocyte membrane enzymes: Na+/K(+)-ATPase
      and Ca(2+)-ATPase. Treatment with capsaicin (0.01-100 microM) caused a transient
      increase in the activities of both enzymes; the effect declined at lower
      concentrations of capsaicin, and no significant effect was observed at 0.01
      microM capsaicin. The effect of capsaicin was fast with a significant (p<0.01)
      activation of enzyme activity observed within minutes of incubation. The findings
      on the effect of capsaicin on human erythrocyte membrane enzymes Na+/K(+)-ATPase
      and Ca(2+)-ATPase signify the importance of the non-neuronal effects of
      capsaicin, and the need for evaluating the physiological impact of high capsaicin
      (capsicum) consumption in some regions of the world.

PMID- 14668916
TI  - Antimutagenic activity of new analogues of fluphenazine.
AB  - Fluphenazine (FPh) exhibited antimutagenic activity in lymphocyte cultures,
      markedly decreasing genotoxic effects of standard mutagenic agents present in
      cell cultures. However, the strong pharmacological activity of this neuroleptic
      drug, together with its serious side effects on the central nervous system,
      limits its use as an antimutagenic compound. In this paper we describe a route of
      chemical synthesis of FPh analogues that are more hydrophilic than the model
      compound, thus probably penetrate more weakly through the blood-brain barrier.
      These new analogues were tested for their antimutagenic and pro-apoptotic
      activities in human lymphocyte cultures, genotoxically damaged in vitro with
      benzo[a]pyrene [40 microM, 30 min] and subsequently cultured for 48 h in the
      presence of the tested compounds. The fluphenazine analogues enhanced apoptosis
      in genotoxically damaged lymphocytes more strongly than the model compound did.
      The increase of apoptotic cell frequency was the highest with compound 4a [2
      (trifluoromethyl)-10-[3-(diethanolamino)-2-hydroxypropyl] phenothiazine]--a 35%
      higher effect than that of fluphenazine. The cytotoxicity of derivative 4a was
      the lowest among the tested compounds; it was 60% lower than that of
      fluphenazine. The antimutagenic effect of 4a was about 10% stronger than that of
      fluphenazine. Compound 4a also had the highest hydrophilicity of the new FPh
      analogues. Compound 4a was chosen for further study as a potentially usable
      antimutagen that would only weakly penetrate the central nervous system.

PMID- 14668917
TI  - The dependence of Fluorescein-PE fluorescence intensity on lipid bilayer state.
      Evaluating the interaction between the probe and lipid molecules.
AB  - The degree of dependence of a lipid bilayer's surface properties on its
      conformational state is still an unresolved question. Surface properties are
      functions of molecular organization in the complex interfacial region. In the
      past, they were frequently measured using fluorescence spectroscopy. Since a
      fluorescent probe provides information on its local environment, there is a need
      to estimate the effect caused by the probe itself. In this paper, we address this
      question by calculating how lipid head-group orientation effects the fluorescence
      intensity of Fluorescein-PE (a probe that is sensitive to surface potential). In
      the theoretical model assumed the lipid bilayer state and the interactions
      between the charged fluorescent probe and the surrounding lipid molecules was
      evaluated. The results of this theoretical analysis were compared with
      experimentally obtained data. A lipid bilayer formed from DPPC was chosen as the
      experimental system, since it exhibits all the major conformational states within
      a narrow temperature range of 30 degrees C-45 degrees C. Fluorescein-PE
      fluorescence intensity depends on local pH, which in turn is sensitive to local
      electrostatic potential in the probe's vicinity. This local electrostatic
      potential is generated by lipid head-group dipole orientation. We have shown that
      the effect of the probe on lipid bilayer properties is limited when the lipid
      bilayer is in the gel phase, whereas it is more pronounced when the membrane is
      liquid-crystalline. This implies that Fluorescein-PE is a good reporter of local
      electrostatic fields when the lipid bilayer is in the gel phase, and is a poor
      reporter when the membrane is in the liquid-crystalline state.

PMID- 14668918
TI  - The chromosomal location of rye AFLP bands.
AB  - 23 AFLP bands were assigned to different rye chromosomes by means of two
      different sets of wheat-rye addition lines. Only one AFLP band could be assigned
      to 4R, and no specific AFLPs were found on the 5R chromosome. Only one AFLP band
      was explicitly assigned to 4R, and no specific AFLPs were found on the 5R
      chromosome. At least seven co-migrating AFLPs showed the same chromosomal
      location in both sets of addition lines. A total of 22 AFLPs were assigned to
      chromosome 1R using wheat-rye substitution lines. Six of them have counterparts
      in one of the addition lines analyzed, but only four have the same chromosomal
      location. Six and four of the total AFLPs located using addition (23) and
      substitution (22) lines segregated in the mapping population DS2 x RXL10, but
      only six were simultaneously assigned to the same chromosome by both approaches.
      Although co-migrating AFLPs could be located on different rye chromosomes using
      addition and substitution lines, we believe that AFLPs can be useful as rye
      chromosome markers.

PMID- 14668919
TI  - An assessment of the resistance gene analogues of Oryza sativa ssp. japonica:
      their presence and structure.
AB  - Rice is the first cereal genome of known draft sequence, and the finished
      sequence for it is now nearly complete. In this paper, we describe a preliminary
      analysis of known rice genes aimed to detect resistance gene analogues of known
      structural classes. Putative resistance genes were identified in a dual approach-
      by using BLASTP searches to identify candidate sequences and by using Hidden
      Markov Models to predict domain presence in the candidates. The set of proteins
      examined was obtained from the publicly available data of TIGR (The Institute for
      Genomic Research). 1744 distinct RGAs were identified, 597 of which belonged to
      the NBS-LRR class. Supplementary data (sequences and annotations) is available on
      the web site http:/gkoczyk.bioinfo.pl/CMBL.

PMID- 14668920
TI  - The total antioxidant capacity of blood plasma during cardiovasculary bypass
      surgery in patients with coronary heart disease.
AB  - We studied he effect of ischemia and reperfusion on the total antioxidant
      capacity (TAC) of blood plasma during cardiopulmonary bypass surgery employing
      the modified St. Thomas Hospital cardioplegic solution. TAC was determined using
      the FRAP method. TAC decreased during surgery, but no further decrease in TAC was
      observed during reperfusion, indicating that it is a relatively stable parameter
      of the antioxidative barrier of the body.

PMID- 14668921
TI  - Culture treatments for enhancing post-thaw recovery of cryopreserved suspension
      cells of potato cv. Desiree.
AB  - An efficient and reproducible protocol has been developed for the
      cryopreservation of cell suspension cultures of the potato (Solanum tuberosum L.)
      cv. Desiree. An evaluation was made of the effectiveness of different pre-culture
      and post-thaw treatments on cell growth, as measured by changes in biomass. Cell
      suspensions were cultured in UM medium supplemented with 0.25, 0.5, 0.625, 0.75
      or 1.0 M sucrose prior to cryopreservation. Sucrose-treated cells were harvested
      from suspension and 0.75 ml packed cell volumes placed in 2 ml capacity
      polypropylene vials with 0.5 ml of chilled cryoprotectant (glycerol 46.0 g 1(-1),
      dimethylsulphoxide 39.0 g 1(-1), sucrose 342.0 g 1(-1) proline 5.0 g 1(-1); pH
      5.8). Cells were frozen at -0.5 degrees C min(-1) from 0 to -35 degrees C, held
      at -35 degrees C for 35 min and stored, for 10 days, in liquid nitrogen (-196
      degrees C). The most effective pre-treatment, in terms of subsequent post-thaw
      cell viability as assessed by fluorescein diacetate uptake or
      triphenyltetrazolium chloride reduction, was culture with 0.75 M sucrose. For
      this treatment, the mean absorbance (490 nm) following triphenyltetrazolium
      chloride reduction was 88% greater (p < 0.05) than control and 59% greater (p <
      0.05) for thawed cells also cultured on supporting filter paper discs.

PMID- 14668922
TI  - Desulfovibrio desulfuricans lipopolysaccharides induce endothelial cell IL-6 and
      IL-8 secretion and E-selectin and VCAM-1 expression.
AB  - The aim of this study was to determine whether Desulfovibrio desulfuricans
      derived LPS stimulate the release of IL-6 and IL-8 from ECs and the expression of
      their adhesion molecules at the transcriptional level. Confluent monolayers of
      HUVEC were incubated in the absence or presence of 20 microg/ml and 60 microg/ml
      LPSs derived from the DdT and DdA bacterial strains. Also, the simultaneous
      stimulation of cells with LPSs and IL-1beta was evaluated. The levels of
      cytokines released were measured using ELISA. LPS-activated HUVEC increased the
      secretion of both IL-6 and IL-8, which was not LPS dose dependent. The expression
      of E-selectin and VCAM-1 was assessed by TR-PCR. The transcripts were detectable
      at all the concentrations (20, 40, 60 microg/ml) of LPSs used. These results
      suggest that D. desulfuricans LPS may activate immune functions in endothelial
      cells and influence the inflammatory response during bacteremia caused by these
      bacteria.

PMID- 14668923
TI  - Dicarboxylate platinum(II) complexes as inhibitors of plasma membrane H(+)-ATPase
      in the yeast Saccharomyces cerevisiae.
AB  - A series of cytotoxic neutral dicarboxylatoplatinum(II) complexes containing
      D(+), L(-) or DL-malate dianion and ethylenediamine or 1-ethylimidazole as
      ligands were examined using ATPase activity assays and the proton extrusion test.
      ATPase activity assays in vitro on plasma membrane H+-ATPase and on mitochondrial
      ATPase were carried out. The concentrations of compounds inhibiting enzyme
      activity to 50 per cent (J50) was determined. The new platinum complexes showed a
      stronger level of inhibition of both ATPases than the reference carboplatin; this
      inhibitory activity is related to a stereoisomeric form of anionic platinum
      ligands. ATPase inhibition in vivo was tested by glucose-stimulated proton
      extrusion and the influence of platinum compounds on this process in yeast cells
      was determined. Significant differences in activity levels were observed between
      those complexes with 1-ethylimidazole and those with ethylenediamine.

PMID- 14668924
TI  - Analysis of high-pressure-induced disruption of human erythrocytes by flow
      cytometry.
AB  - High-pressure-induced hemolysis is suppressed by pretreating human erythrocytes
      at 49 degrees C, or enhanced by pretreatment with trypsin. So, the response of
      these pretreated cells to a pressure of 200 MPa was examined using flow
      cytometry. In the case of intact erythrocytes, a major product was fragmented
      particles. From 49 degrees C-pretreated cells, vesicles were mainly released.
      Trypsin-pretreated cells mainly produced open ghosts. Additionally, intact
      erythrocytes, 49 degrees C-pretreated ones, and trypsin-pretreated ones also
      released at 200 MPa vesicles of diameter 464 +/- 9, 259 +/- 18, and 574 +/- 16
      nm, respectively. These results suggest that mother cells, fragmented particles,
      vesicles, and open ghosts from 200 MPa-treated erythrocytes are easily monitored
      by flow cytometry and that the size of released vesicles may also be an important
      factor in high-pressure-induced hemolysis.

PMID- 14668925
TI  - Force generation by cellular motors.
AB  - Cell motility processes in non-muscle cells depend on the activity of motor
      proteins that bind to either microtubules or actin filaments. From presently
      available data it must be concluded that the driving force is generated by
      transient interaction of the respective motors with microtubules or actin
      filaments which then activates the binding and hydrolysis of ATP. This reaction
      results in an abrupt discharge of the motor molecule, the direction of which is
      determined by the spatial orientation of its binding to the helical and polar
      vehicle. The latter is thereby propelled in its length direction and
      simultaneously undergoes an axial rotation, while the expelled motor exerts an
      oppositely directed current in the surrounding fluid, comparable to jet
      propulsion. Force production, propulsion velocities and energy requirements known
      from in vitro studies comply with those derived from the theory. The theory opens
      new ways for the understanding of cellular activities such as particle transport,
      mitosis and morphodynamics.

PMID- 14668926
TI  - Cellular organelle transport and positioning by plasma streaming.
AB  - Our analysis of known data reveals that translocations of passively movable
      cellular organelles from tiny granules up to large cell nuclei can be ascribed to
      transport by streaming cytoplasm. The various behaviours, such as velocity
      changes during more or less interrupted movements, forth and back shuttling and
      particle rotation result from different types of plasma circulation. Fast
      movements over long distances, as observed in the large characean internodial
      cells occur in strong streams generated by myosin in bundles of actin filaments
      in the direction of the barbed filament ends. Slow movements with frequent
      reversions of the direction are typical for neuronal axons, in which an
      anterograde plasma flow, produced in a thin layer of membrane-attached actin
      filaments, is compensated by a retrograde stream, produced by dynein activity in
      the central bundle of microtubules. Here particle rotation is due to steep flow
      velocity gradients, and frequent changes of particle movements result from minor
      particle displacements in radial directions. Similar shuttling of pigment
      granules in the lobes of epidermal chromatophores results from the same
      mechanism, whereby the centrifugal movement along astral microtubules is due to
      flow generated by excess of kinesin activity and the centripetal movement to the
      plasma recycling through the intermicrotubular space. If the streaming pattern is
      reversed by switching to excess dynein activity, the moving granules are trapped
      in the high microtubule density at the aster center. The presence of larger
      bodies in asters disturbs the regular, kinesin-dependent microtubule distribution
      in such a way that a superimposed centrifugal plasma flow develops in the
      microtubule-dense layer along them, which is recycled in the microtubule-free
      space, created by their presence. Consequently, at excess kinesin activity,
      nuclei, mitochondria as well as chromosome fragments move towards the aster
      center until they reach a dynamically stabilized position that depends on the
      local microtubule density. These various behaviours are not rationally
      explainable by models based on a mechanical stepping along microtubules or actin
      filaments.

PMID- 14668927
TI  - Objectives and strategies for rheumatoid arthritis therapy: yesterday vs. today.
AB  - The goals for the treatment of rheumatoid arthritis have changed from slowing the
      disease process only after a definitive diagnosis is made, to intervening early
      to minimize disease activity and achieve and maintain remission. To meet the new
      goals, both monotherapy and combination therapy must be administered not only
      early but aggressively, and aggressive therapy must be sustained. In addition,
      the efficacy of this treatment design can only be achieved if disease activity is
      monitored.

PMID- 14668928
TI  - Appropriate and effective rheumatoid arthritis control: role of TNF antagonists.
AB  - There are several unmet needs for the appropriate and effective control of
      rheumatoid arthritis (RA), namely rapid onset of action; effectiveness in disease
      modifying antirheumatic drug (DMARD)-resistant disease, including improvements in
      signs and symptoms, disability, quality of life and radiographic progression;
      sustainability of response; and a good risk/benefit ratio. Tumor necrosis factor
      (TNF) antagonists appear to address these needs and consequently have set a new
      therapeutic standard for the treatment of RA and have made it possible for
      rheumatologists to target remission as a primary therapeutic goal.

PMID- 14668929
TI  - Role of adalimumab, a novel TNF antagonist in advancing rheumatoid arthritis
      control.
AB  - Adalimumab was approved by the U.S. Food and Drug Administration in 2002 for the
      treatment of moderate to severe rheumatoid arthritis and was granted approval
      from the European Medicines Evaluation Agency (EMEA) in September 2003. The
      standard dose is 40 mg given subcutaneously every other week, and the drug can be
      used alone or in combination with disease-modifying antirheumatic drugs such as
      methotrexate. The efficacy of adalimumab has been demonstrated in clinical trials
      with more than 2400 patients. In these trials, adalimumab has acted rapidly to
      reduce the signs and symptoms of disease, with responses sustained over the long
      term. The significant inhibition of disease progression seen with adalimumab has
      led to significant improvements in physical function and health-related quality
      of life. Data from the clinical safety database in nearly 2500 patients have also
      shown that the drug is generally safe and well-tolerated.

PMID- 14668930
TI  - Olmesartan, an AT1-selective antihypertensive agent.
AB  - Olmesartan is an angiotensin II receptor antagonist indicated for the treatment
      of essential hypertension. Angiotensin II is an important hormonal effector and
      end-product of the renin-angiotensin system. When it binds to its endogenous
      receptor sites, it causes widespread vasoconstriction and a subsequent increase
      in blood pressure. Olmesartan works by selectively binding to AT(1) against the
      pathophysiologic events leading to diabetic nephropathy and cardiovascular
      morbidity/mortality. This end-organ protection is independent of olmesartan's
      blood pressure lowering properties and is therefore thought to be mediated by
      different mechanisms. In summary, olmesartan has an efficacy profile superior to
      other available antihypertensive agents, with a tolerability profile comparable
      to that of placebo. In addition, the convenience of its once-daily dosing means
      that olmesartan should be considered not only as an alternative, but also as a
      first-line treatment for patients with mild to severe essential hypertension.
      Thus, olmesartan appears to be a very promising new therapy for the treatment of
      hypertension.

PMID- 14668931
TI  - Interferon gene therapy for the treatment of cancer and viral infections.
AB  - Interferons exhibit strong antiproliferative, antiviral and immunomodulatory
      properties. A combination of these properties makes them ideal candidates for the
      treatment of cancer and viral infections. However, their use as a protein
      therapeutic is limited due to their short serum half-life and certain undesirable
      side-effects. Some of these limitations are likely to be overcome by using
      interferons in a gene therapy modality. Gene therapy offers the advantage of
      generating higher sustained local concentration of this cytokine. In addition, it
      is possible to target the desired tissues and/or tumors by using specific
      promoters and to modulate the levels of the cytokine by using regulatable
      promoters. Results from studies in experimental tumor models of gene therapy for
      cancer and for certain viral infections have been encouraging and suggest that
      this may be a feasible and attractive alternative to interferon protein therapy.

PMID- 14668932
TI  - Nesiritide in perspective: evolving approaches to the management of acute
      decompensated heart failure.
AB  - Nesiritide is currently indicated for the management of acute decompensated heart
      failure defined by the presence of volume overload and dyspnea at rest or with
      minimal activities. Hypotension and cardiogenic shock are the major
      contraindications to nesiritide use. The recommended dosing schedule is a 2 micro
      g/kg bolus followed by a 0.01 micro g/kg/min infusion. Some clinicians, however,
      opt to begin the infusion at the recommended dose without a loading bolus in
      nonemergency situations. The average duration of infusion in the Vasodilation in
      the Management of Acute Congestive Heart Failure (VMAC) trial was approximately
      28 hours. Clinical efficacy endpoints included resolution of dyspnea and
      reduction of volume overload. Appropriate oral drug therapy for heart failure
      management should be initiated during the nesiritide infusion. The 15-year
      transition of B-type natriuretic peptide from a newly discovered physiologic
      entity to clinical use in the diagnosis and treatment of heart failure provides a
      remarkable example of rapid technological improvement and enhanced clinical
      understanding. As with most advances, the process of rolling back the frontiers
      of knowledge has posed even more questions. However, we must not overlook the
      progress to date, simply because all of the answers are not yet available.

PMID- 14668933
TI  - Influence of genetic markers on survival in non-small cell lung cancer.
AB  - Cisplatin or carboplatin is commonly used with gemcitabine, docetaxel, paclitaxel
      or vinorelbine as chemotherapy doublets in the treatment of advanced non-small
      cell lung cancer. Several randomized trials have failed to identify major
      differences in survival between any of these doublets. This lack of evidence for
      improvement in survival with any chemotherapy regimen has created a tabula rasa
      in which no more large randomized trials should be conducted with out including a
      genetic analysis. Patients see survival as their major concern, and other
      considerations, such as cost of treatment and qualify of life, are relegated to
      lower positions. Genetic alterations related to the transcription-coupled repair
      pathway of the nucleotide excision repair system (TC-NER) have revealed the
      subset of patients who are resistant to cisplatin. TC-NER involves genes that are
      deficient in rare inborn disorders such as Cockayne syndrome and xeroderma
      pigmentosum. For a long time, ERCC1 mRNA levels have been known to correlate with
      DNA repair capacity in various tissues. Levels of DNA cisplatin adducts in
      peripheral blood and buccal mucosa cells predict chemotherapy response, and high
      ERCC1 mRNA levels have been related to chemoresistance in ovarian cancer and in
      malignant lymphocytes from chronic lymphocytic leukemia. Moreover , in some
      instances, mRNA expression has been correlated with polymorphisms. Overexpression
      of ERCC1 correlates with poor survival gemcitabine/cisplatin-treated non-small
      cell lung cancer patients. An ongoing customized ERCC1-based chemotherapy trial
      has been established on this knowledge. Patients are randomized to the control
      arm of cisplatin/docetaxel is combined with cisplatin or gemcitabine according to
      ERCC1 levels. To date, 80 patients have been included. At the preclinical level,
      ERCC1 and XPD mRNA expression correlate with each other, and overexpression of
      XPD causes selective cisplatin resistance in human tumor cell lines. Some XPD
      polymorphisms have been associated with lower DNA repair capacity. In our
      experience, time to disease progression is significantly higher in
      gemcitabine/cisplatin-treated patients with the Lys751Gln genotype (9.6 months)
      than in those with the Lys751Lys genotype (4.2 months; p = 0.03). Other
      polymorphisms involved in parallel DNA repair systems may well provide the same
      information, indicating a high degree of biological redundancy. The
      overexpression of the subunit M1 of ribonucleotide reductase (RRM1) has been
      linked to gemcitabine resistance in our retrospective assessment. Preliminary
      findings indicate that a subset of gemcitabine/cisplatin-treated patients with
      low ERCC1 and RRM1 mRNA levels show a significantly longer survival. This
      highlights the possibilities of individually tailored chemotherapy. However, in
      patients treated with cisplatin/vinorelbine, the opposite effect has been
      observed. Patients with Lys751Lys had a longer time to progression. When
      docetaxel was added to gemcitabine/cisplatin, patients with Lys751Lys also had
      better survival. Our findings indicate that TC-NER status can help to decide
      between cisplatin/gemcitabine and docetaxel/ cisplatin. TC-NER-dependent activity
      is similar to other anticancer agents that cause DNA-binding enzymes to kill
      cells (topoisomerase inhibitors). At least 50% of non-small cell lung cancer
      patients harbor Lys751Lys and can benefit from docetaxel/ cisplatin treatment.
      Genes involved in spindle formation, centrosome functions and mRNA transport
      along the microtubule tracks should provide further information on potential
      markers of docetaxel resistance.

PMID- 14668934
TI  - Wound healing: the role of growth factors.
AB  - Wound healing is a complex biological process that requires cellular interactions
      between a variety of cells, including fibroblasts, myofibroblasts, smooth muscle
      cells, endothelial cells, keratinocytes and immune cells. These interactions are
      mediated by numerous factors such as growth factors, hormones, blood components
      and second messengers. Several growth factors that are released at the wound site
      are presumed to be necessary for wound healing. These include epidermal growth
      factor (EGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF),
      keratinocyte growth factor (KGF), platelet-derived growth factor (PDGF),
      transforming growth factor (TGF) and vascular endothelial growth factor (VEGF).
      The clinical use of growth factors to stimulate the healing of wounds is
      currently being investigated. Several growth factors, including PDGF, FGF-2, IGF
      and KGF, have been used in clinical trials, and PDGF is currently approved for
      use in human medicine.

PMID- 14668935
TI  - Clinical impact of drug-drug interactions with systemic azole antifungals.
AB  - The number of drug-drug interactions is remarkably high among hospitalized
      patients receiving systemic azole antifungal agents. Recent estimates suggest
      that as many as 95% of hospitalized patients treated with azole antifungals may
      receive medications capable of producing a major or moderate pharmacokinetic
      interaction. The antifungal properties of the azoles stem from their propensity
      to inhibit fungal cytochrome P-450 enzymes. In humans, however, azole antifungals
      also interfere with several hepatic and intestinal cytochrome P-450 isoenzymes
      responsible for the metabolism of numerous drugs. As a result, the azole
      antifungals have drug-drug interactions with a plethora of drug classes,
      including H(1)-antihistamines, antineoplastics, steroids, antimicrobials,
      antiretrovirals, opioids, long acting barbiturates, cardiovascular agents,
      psychotropics and oral contraceptives. These interactions are so numerous that it
      is extremely difficult to remember them all and would be even harder to
      prospectively predict their consequences in an individual patient. In fact, any
      drug that shares the same cytochrome P-450 isoenzymes for metabolism may
      potentially to give rise to drug-drug interactions in vivo. Patients with
      specific polymorphisms are probably at especially high risk. Certain drug
      combinations with azoles should be absolutely avoided, while other combinations
      may be prescribed provided monitoring of drug levels is undertaken, dosage
      reduction of one or more of the drugs is made (as appropriate) and/or careful
      monitoring of clinical parameters is performed.

PMID- 14668936
TI  - Mechanisms underlying cancer-induced symptoms.
AB  - In addition to the physical and emotional suffering induced by the diagnosis of
      cancer, patients are subjected to additional discomfort and suffering from
      symptoms induced by both the disease and its treatment. While an increasing
      amount of clinical and basic science research has focused on these issues, our
      understanding of the mechanisms underlying cancer-related symptoms remains
      incomplete. This article summarizes what is known about the mechanisms underlying
      the common symptoms of pain, cachexia, nausea and vomiting, dyspnea, fatigue and
      mood disorders, as well as the implications of these findings for therapeutic
      intervention.

PMID- 14668937
TI  - Incretins and their analogues as new antidiabetic drugs.
AB  - Glucagon-like peptide 1 (GLP-1) is a gut (incretin) hormone with multiple actions
      that could potentially contribute to an antidiabetic effect. This includes: (a)
      glucose-dependent insulinotropic actions; (b) glucagonostatic actions; (c) a
      reduction in appetite/promotion of satiety leading to reduced food intake and
      weight reduction; (d) the deceleration of gastric emptying; and (e) the
      stimulation of islet growth, differentiation and regeneration. Thus, multiple
      aspects of the type 2 diabetic phenotype can potentially be improved or even
      corrected by GLP-1. The native gut hormone, however, after intravenous injection
      or absorption from subcutaneous depots, is proteolytically degraded and
      eliminated from the circulation too quickly to be useful for the treatment of
      diabetes. GLP-1 derivatives (receptor agonists) with prolonged pharmacokinetics
      that promise a potential for clinical use in the near future are being developed.

PMID- 14668938
TI  - In silico approaches, and in vitro and in vivo experiments to predict induction
      of drug metabolism.
AB  - Despite being described more than 40 years ago, the molecular mechanism that
      regulates hepatic induction of cytochromes P450 and other drug-metabolizing
      enzymes and drug transporters by xenobiotics has remained enigmatic until
      recently. A major breakthrough was the discovery of the orphan nuclear receptors
      pregnane X receptor and constitutive androstane receptor playing key roles as
      species-specific xenosensors in this induction response. Using this newly
      acquired knowledge, the human induction response can now be more accurately
      predicted. This is of considerable clinical importance, since induction of
      cytochrome P450s and other enzymes can lead to unwanted drug-drug interactions,
      adverse drug reactions and drug toxicity. In this review, in vitro, in vivo and
      in silico techniques are discussed that can identify troublesome compounds at an
      early stage and that can help to design new, safer medicines faster.

PMID- 14668939
TI  - Pharmacological manipulation of glutamate transport.
AB  - L-Glutamic acid acts as the major excitatory neurotransmitter and, at the same
      time, represents a potential neurotoxin for the mammalian central nervous system
      (CNS). The termination of excitatory transmission and the maintenance of
      physiologic levels of extracellular glutamate, which is necessary to prevent
      excitotoxicity, are prominently mediated by a family of high-affinity sodium
      dependent excitatory amino acid transporters (EAATs). Five subtypes of EAATs have
      been cloned, possessing distinct pharmacology, localization, sensitivity to
      transport inhibitors and modulatory mechanisms. Expression and activity of EAATs
      have been shown to be amenable to fine endogenous and, potentially,
      pharmacological regulation by substrate itself, growth factors, second
      messengers, hormones, biological oxidants, inflammatory mediators and
      pathological conditions. The present review describes basic pharmacological
      studies, mostly performed on animal models or cell preparations, in order to
      obtain an updated picture of the known regulatory mechanisms of single EAAT
      expression and activity. New insight into molecular pathways involved in EAAT
      regulation will allow pharmacological manipulation of excitatory CNS activity,
      possibly avoiding adverse effects of glutamate receptor blockade.

PMID- 14668940
TI  - Bcl-xL as an antiapoptotic molecule for cardiomyocytes.
AB  - It is now widely accepted that two forms of cell death, apoptosis and necrosis,
      occur in cardiomyocytes, and increasing evidence indicates that apoptosis plays
      an important role in the pathophysiology of cardiovascular diseases. Currently,
      two major pathways in the induction of apoptosis are known to occur in
      cardiomyocytes, the mitochondrial pathway and the death receptor pathway. Bcl-2
      family proteins are key regulators of apoptosis in the mitochondrial pathway.
      Among them, Bcl-x(L), which is structurally similar to Bcl-2 and functions as an
      antiapoptotic molecule, is involved in diseases such as ischemic heart diseases
      and heart failure. In this review, we focus on the role of Bcl-x(L) in apoptosis
      in cardiomyocytes and discuss the potential use of Bcl-x(L) as a cardioprotective
      therapy for cardiac diseases.

PMID- 14668941
TI  - Possible involvement of the ERK signaling cascade in bipolar disorder: behavioral
      leads from the study of mutant mice.
AB  - Despite the devastating impact that bipolar disorder has on the lives of millions
      worldwide, little is known for certain about its etiology or pathophysiology.
      Whereas research has traditionally focused on biogenic amines, it is becoming
      increasingly more apparent that intracellular pathways are involved in the
      etiology and treatment of the disease and that a true understanding of the
      pathophysiology of bipolar disorder must address its neurobiology at different
      physiological levels, that is, molecular, cellular, systems and behavioral
      levels. There is now considerable biochemical evidence that the antimanic agents
      lithium and valproate robustly activate the ERK signaling cascade in
      therapeutically relevant paradigms. This raises the possibility that this pathway
      may play a role in the antimanic effects of these agents. The present paper
      reviews behavioral studies that may shed light on the involvement of the ERK
      pathway in affective-like behaviors in animals. The available literature suggests
      that genetic manipulations of the brain-derived neurotrophic factor (BDNF)-ERK
      kinase pathway produces a variety of changes in affective-like behaviors, with
      most changes consistent with manic-like behavior. Thus, overall, mice with
      targeted mutation of the BDNF gene exhibited increased spontaneous locomotion and
      increased response to acute amphetamine, altered response to chronic cocaine,
      increased aggression, increase in risk-taking behavior, as demonstrated by time
      spent in the center of an open field, and changes in eating patterns. Although it
      has to be acknowledged that the currently available behavioral data from the BDNF
      ERK pathway mutants is less than ideal to offer real substantiation relating this
      pathway to bipolar disorder, the data still supports the possibility that this
      pathway modulates manic-like behavior in animals, and perhaps mania in humans.

PMID- 14668942
TI  - Molecule of the month. Cinacalcet hydrochloride.

PMID- 14668943
TI  - Recent advances in nephrology.
AB  - The World Congress of Nephrology was held in Berlin, Germany, June 8-12, 2003.
      The meeting offered the newest advances in basic and clinical nephrology science
      and was attended by about 9,000 scientists and clinicians from around the world.
      During the congress, results of the treatment of Fabry's disease with enzyme
      replacement therapy, the results of the treatment of anemia in patients with
      chronic kidney disease with new erythropoietic agents (darbepoetin alfa,
      continuous erythropoiesis receptor activator), and the management of secondary
      hyperparathyroidism and calcium-phosphorus disorders in uremia with calcimimetic
      agents and new phosphate binders, such as lanthanum carbonate, were discussed.
      Furthermore, recent studies evaluating the efficacy and safety of new
      immunosuppressive agents and their combination for the treatment of renal
      transplant recipients were also presented.

PMID- 14668944
TI  - The potential role of antileukotriene drugs in atherosclerosis.
AB  - Developing drugs to treat atherosclerosis is a daunting task. However, recent
      studies of advanced human atherosclerotic lesions have yielded new information on
      potential mechanisms of inflammation and immune responses in late-stage human
      atherosclerosis. As leukotrienes (LTs) are among the most powerful inflammatory
      mediators known and because the 5-lipoxygenase pathway is expressed in diseased
      arteries, the roles of LTs in atherogenesis merit consideration. It is also of
      interest to consider pharmacological strategies to develop anti-LT drugs in
      atherogenesis.

PMID- 14668945
TI  - Physiological function of ABCG1.
AB  - Since ATP-binding cassette transporter A1 (ABCA1) was discovered as the cause of
      Tangier disease and familial high-density lipoprotein (HDL) deficiency, many
      investigators have been interested in the relationship between ABC transporters
      and the mechanism underlying abnormal lipid metabolism. ABCG1 is an ABC half
      transporter that facilitates efflux excess cholesterol from macrophages. To
      elucidate the potential physiological role of ABCG1, we have initiated a series
      of studies overexpressing ABCG1, using an adenovirus vector (rABCG1-Adv) in C57BL
      mice. Overexpression of ABCG1 in the liver of mice using recombinant ABCG1
      vectors results in decreased plasma HDL levels and increased biliary cholesterol
      excretion, and indicates that ABCG1 can modulate plasma lipoprotein levels in
      vivo. ABCG1 and the other ABC transporters might play an important role in
      cholesterol homeostasis, especially in the liver.

PMID- 14668946
TI  - 4-Hydroxyphenylpyruvate dioxygenase as a drug discovery target.
AB  - The molecular mechanism for 4-hydroxyphenylpyruvate dioxygenase (4-HPPD)
      inhibition by nitisinone, a recently approved new drug for the treatment of
      hereditary tyrosinemia type I, has been satisfactorily explained by its action as
      an analogue to the substrate 4-hydroxyphenylpyruvate. In addition, a novel
      induced conformationally restricted 4-HPPD inhibitor, diketonitrile, which serves
      as a nonclassical bioisostere for rigid cyclic 1,3-diketone derivatives, has been
      introduced. Further application of the molecular mode of action of nitisinone in
      rational design of potential inhibitors for alpha-ketoglutarate-coupled
      dioxygenases is discussed.

PMID- 14668947
TI  - Cellular and molecular events underlying ischemia-induced neuronal apoptosis.
AB  - Neurons subjected to ischemia undergo necrosis or apoptosis depending on their
      anatomic distribution and the severity and duration of ischemia. Recent work has
      shown that apoptosis can occur in some settings, primarily within the ischemic
      penumbra. It is recognized that both mitochondrial and death-receptor pathways
      are involved in the transduction of apoptotic signals in the context of cerebral
      ischemia. Recent data also highlight the pivotal role of caspase 3 in the
      execution of ischemia-induced apoptosis, although a caspase-independent pathway
      is gaining increasing attention. In this review, we examine some of these
      findings and their potential therapeutic implications for ischemic stroke.

PMID- 14668948
TI  - The role of the hypocretinergic system in the integration of networks that
      dictate the states of arousal.
AB  - Recent studies have led to the discovery of a neuropeptide system that regulates
      arousal states. The hypocretins (hcrt1 and hcrt2, also called the orexins) are
      neuropeptides of related sequence derived from the same precursor whose
      expression is restricted to a few thousand neurons of the lateral hypothalamus.
      Two G-protein-coupled receptors for the hypocretins have been identified, and
      these have different distributions within the central nervous system and
      differential affinities for the two hypocretins. Hypocretin fibers project
      throughout the brain, including several areas implicated in cardiovascular
      function and regulation of the sleep-wake cycle. Central administration of
      synthetic hypocretin-1 affects blood pressure, hormone secretion and locomotor
      activity, and increases wakefulness while suppressing rapid eye movement sleep.
      Most human patients with narcolepsy have greatly reduced levels of hypocretin
      peptides in their cerebral spinal fluid and no or barely detectable hypocretin
      neurons in their hypothalami, suggestive of autoimmune attack. Development of
      nonpeptidergic hypocretin antagonists may prove useful in sleep disorders,
      whereas hypocretin agonists may be used to treat narcolepsy and excessive daytime
      sleepiness. The hypocretins are also an excellent target for the pharmacological
      treatment of the deregulated arousal state that characterizes depression or
      addictive behavior.

PMID- 14668949
TI  - Modulation of metabotropic glutamate receptors as potential treatment for acute
      and chronic neurodegenerative disorders.
AB  - It is well established that in both animal models and humans, traumatic or
      ischemic insults to the brain or spinal cord cause an excessive release of
      excitatory amino acids, including glutamate. Moreover, multiple in vivo and in
      vitro studies show that excessive release of glutamate, and subsequent activation
      of ionotropic (iGluRs) and metabotropic (mGluRs) classes of glutamate receptors,
      cause neuronal cell death through either necrosis or apoptosis. Although studies
      in adult animals have demonstrated the neuroprotective effects of inhibiting
      iGluRs following central nervous system injury, results from human trials have
      been disappointing. Furthermore, treatment with iGluR antagonists alone can
      exacerbate apoptotic cell death in the developing brain. Recently, an alternative
      approach has examined the modulatory effects of mGluRs on excitotoxicity and
      neuronal cell death. Experimental studies have shown that modulation of all
      groups (I, II, III) of mGluR can be neuroprotective, and that effects across
      groups may be additive. Group I mGluR includes mGluR1 and mGluR5. Although these
      receptors show certain common signal transduction pathways, activation or
      inhibition of these two receptors have very different actions on necrotic and
      apoptotic neuronal cell death. Recent work has shown that activation of mGluR5
      significantly attenuates neuronal apoptosis in a variety of model systems. Given
      the proposed role of apoptotic cell death in both acute and chronic
      neurodegenerative disorders, these observations suggest that this receptor may be
      an interesting novel target for the development of effective neuroprotective
      treatment.

PMID- 14668950
TI  - The complex biology of the receptor for the insulin-like growth factor-1.
AB  - The receptor for the insulin-like growth factor-1 (IGF-1R) controls a wide
      variety of cellular functions. IGF-1R is a tyrosine kinase receptor that is
      activated by the binding of a ligand to the extracellular domain. There are three
      ligands for IGF-1R: IGF-I, IGF-II and insulin at supraphysiological
      concentrations. The binding of the ligand activates the catalytic activity of the
      tyrosine kinase domain, which in turn causes the autophosphorylation of IGF-1R.
      As a consequence of autophosphorylation, the activated IGF-1R sends a potent
      mitogenic signal to the cell nucleus. It has been clearly shown that an
      overexpressed and activated IGF-1R is quasi-obligatory for the establishment of a
      malignant cell phenotype. Interestingly, the targeting of IGF-1R can reverse the
      malignant phenotype in cancer cells, without affecting the biology of normal
      cells. For these reasons, IGF-1R seems to be a very promising candidate target
      for cancer therapy. In addition, IGF-1R protects cells from apoptosis and
      promotes cell growth and proliferation. However, more recent studies have also
      shown that IGF-1R regulates cell adhesion and motility, and, in certain cellular
      contexts, can induce differentiation. Indeed, the biology of the IGF-1R appears
      more complex than previously thought. The goal of this review is to describe the
      multiple functions displayed by IGF-1R in cell biology.

PMID- 14668951
TI  - Molecule of the month. Diquafosol tetrasodium.

PMID- 14668952
TI  - Cardiovascular research in Australia.
AB  - The Baker Heart Research Institute (BHRI), one of Australia's finest research
      facilities, played host to the 27th annual Australasian Section of the
      International Society for Heart Research meeting, New Science at the Heart of New
      Therapies, August 7-9, 2003. This report discusses the keynote lectures
      (Prophylactic Effects of Statins on Ischaemic Heart Disease, Diet and Wine as
      Cardioprotection, Artificial Heart Technology and Therapeutics) and the symposia
      presented at the meeting. The topics for the symposia were vascular regulatory
      mechanisms, adaptation and regulation of myocardial metabolism, signaling and
      mechanisms in hypertrophy/fibrosis, gender and cardiovascular disease and the
      dilemma of diabetes. The high standard of the presented material clearly
      demonstrates the strength that Australia in general and the BHRI in particular
      have in cardiovascular research.

PMID- 14668953
TI  - [Successes and research challenges in the German Democratic Republic. Concept and
      effect on health care policy].

PMID- 14668954
TI  - [The journal Nuklearmedizin: does the subtitle Journal of Functional and
      Molecular Imaging describe the current practice of publishing?].
AB  - AIM AND METHOD: The scientific publications in the 2001 and 2002 issues of the
      journal Nuklearmedizin. Journal of Functional and Molecular Imaging were analyzed
      retrospectively with regard to molecular imaging/therapy content criteria.
      RESULTS: Out of a total of 82 original papers and case reports 83% were based on
      molecular or functional methods, 91% of them using commercially available
      tracers, 57% were categorized as molecular imaging, 11% as molecular therapy, 12%
      as functional imaging and 2% as functional therapy. 3% of the studies were
      categorized as experimental research. Researchers from medical specialties other
      than nuclear medicine were co-authors in 71% of the articles, they were rooted in
      basic medical sciences in 16%. Of the 65 original papers 51% were predominantly
      dedicated to methodological development; 49% of them were prospective studies.
      CONCLUSION: The subtitle Journal of Functional and Molecular Imaging describes
      the current practice of publishing in Nuklearmedizin. The number of authors from
      other specialties shows that multidisciplinary integration within the field of
      molecular imaging is performed. Nevertheless, more integration of basic medical
      sciences is needed. Nuklearmedizin contributes to the insight of molecular
      imaging and to its clinical application in humans.

PMID- 14668955
TI  - [Analysis of (18)F-FDG uptake patterns in PET for diagnosis of septic and aseptic
      loosening after total hip arthroplasty].
AB  - AIM: Identification of typical patterns for fluorodeoxy-glucose (FDG) uptake in
      positron emission tomography (PET) to detect aseptic loosening of hip prosthesis
      (ace-tabular and/or femoral component) and prosthetic infection. METHODS: 18
      patients with painful hip prosthesis underwent PET using a dedicated full ring
      scanner after application of 200-300 MBq FDG. The interface between bone and
      surrounding soft tissue or bone as displayed on coronal slices was divided into
      12 segments in accordance with the classifications of Delee and Gruen. FDG uptake
      in each of the segments was scored (0-3) by two independent observers.
      Intraoperative findings were regarded as the gold standard. RESULTS: After
      surgical revision 14 acetabular components and 9 femoral components were found to
      be loose and prosthetic infection was present in 7 prostheses. Loosening of the
      acetabular component was correlated to enhanced uptake in the middle of the
      acetabular interface, while loosening of the femoral component was correlated to
      enhanced uptake in the proximal and middle segment of the lateral femoral
      interface and the proximal segment of the medial femoral interface. A similar
      pattern was found in prosthetic infection with high uptake along the middle
      portion of the lateral femoral interface. In 6 of 7 infected prostheses loosening
      of the acetabular and of the femoral component was present. Taking the typical
      uptake patterns as criteria for loosening and grade 3 uptake as an additional
      criterion for septic loosening the accuracy of PET imaging in the detection of
      loosening of the acetabular or the femoral component and of prosthetic infection
      was 72, 78 and 89%, respectively. CONCLUSION: This pilot study presents FDG-PET
      as a promising diagnostic tool for patients with painful hip prostheses. Its
      clinical value should be evaluated in a larger patient population.

PMID- 14668956
TI  - Iodine excretion during stimulation with rhTSH in differentiated thyroid
      carcinoma.
AB  - AIM: Elevated iodine intake is a serious problem in the diagnostic and
      therapeutic application of (131)iodine in patients with differentiated thyroid
      cancer. Therefore, iodine avoidance is necessary 3 months in advance.
      Additionally, endogenous stimulation requires withdrawal of thyroid hormone
      substitution for 4 weeks. Exogenous stimulation using recombinant human TSH
      (rhTSH) enables the continuous substitution of levothyroxine, which contains
      65.4% of its molecular weight in iodine. Thus, a substantial source of iodine
      intake is maintained during exogenous stimulation. Although this amount of stable
      iodine is comparable to the iodine intake in regions of normal iodine supply, it
      may reduce the accumulation of radioiodine in thyroid carcinoma tissue. The aim
      of this study was to assess the iodine excretion depending on different ways of
      stimulation. METHODS: Iodine excretion was measured in 146 patients in the long
      term follow up after differentiated thyroid carcinoma. Patients were separated
      into 2 groups, those on hormone withdrawal (G I) and rhTSH-stimulated patients on
      hormone substitution (G II). RESULTS: Iodine excretion was significantly lower in
      hypothyroid patients (G I, median 50 micro g/l, range: 25-600 micro g/l) than in
      those under levothyroxine medication (G II, median 75 micro g/l, 25-600 micro
      g/l, p <0.027). TSH in G I (median 57.0 micro U/ml, range: 14.4-183 micro U/ml)
      was significantly lower (p <0.001) than in G II (117 micro U/ml, 32.2-281 micro
      U/ml). CONCLUSION: Iodine excretion was higher in patients under rhTSH
      stimulation than after hormone withdrawal. This may indicate an increased iodine
      pool in rhTSH-stimulated patients (deiodination of levothyroxine), thus limiting
      the sensitivity of radioiodine scanning to the level of endogenous stimulation
      despite significantly higher TSH levels during rhTSH-stimulation.

PMID- 14668957
TI  - Multicenter study differentiated thyroid carcinoma (MSDS). Diminished acceptance
      of adjuvant external beam radiotherapy.
AB  - AIM: The Multicenter Study Differentiated Thyroid Carcinoma (MSDS) is an ongoing
      study in Germany, Austria, and Switzerland on the clinical benefit of adjuvant
      external beam radiotherapy (RTx) for locally invasive differentiated thyroid
      carcinoma (DTC) in TNM stages pT4 pN0/1/x M0/x (5th ed. 1997). METHODS: MSDS was
      designed as a prospective randomized trial. Patients receive thyroidectomy,
      radioiodine therapy (RIT) to ablate the thyroid remnant, and TSH-suppressive L
      thyroxine therapy with or without RTx after documented elimination of cervical
      iodine-131 uptake (http://msds-studie.uni-muenster.de). RESULTS: 311 patients
      were enrolled between January 2000 and March 2003. 279 patients met the trial's
      inclusion criteria. 45 consented to randomization, of whom 17 were randomized
      into treatment arm A (RTx) and 18 into arm B (no RTx). Advised by the trial's
      independent Data Monitoring and Safety Committee, the MSDS steering committee
      decided to terminate randomization in April 2003 and continue MSDS as a
      prospective cohort study. 23 of the 234 patients in the observation arm of the
      trial were prescribed RTx by their physicians. Thus, 14% of the trial cohort were
      randomized or assigned to receive RTx (in-tention-to-treat analysis). In
      contrast, at least 44% of all patients with pT4 papillary DTC in Germany in the
      nation-wide PCES study underwent RTx in 1996 (p <0.001, chi(2)-test).
      CONCLUSIONS: Acceptance of external beam RTx as a treatment modality for DTC has
      receded to a degree that accrual of a sufficient number of patients for a
      randomized trial has been impossible. Observation of the trial cohort is
      continued in order to assess clinical event rates with and without RTx and
      chronic RTx toxicity.

PMID- 14668958
TI  - [Radiation doses deriving from patients treated with (166)Ho-ferric hydroxide].
AB  - AIM: To estimate radiation doses deriving from patients treated with (166)Ho
      ferric hydroxide. METHODS: For radiation synoviorthesis about 900 +/- 100 MBq
      (166)Ho ferric hydroxide was injected into the knee joint of 16 patients. To
      estimate the radiation exposure of persons in the neighbourhood of the patients
      measurements of the dose rates were performed at 0.5 m, 1 m and 2 m distance of
      the treated joint 10 min after tracer injection. Measurements were carried out
      with and without radiation protection devices of the syringe. RESULTS: The
      initial values of the dose rate were 11.9 micro Sv/h at 0.5 m, 3.5 micro Sv/h at
      1 m and 1 micro Sv/h at 2 m distance, respectively. The whole body doses were 2.9
      micro Sv for the physician and 4.6 micro Sv for the technologist. The finger
      doses for the technologist and the physician were ranging from 65 to 111 micro
      Sv. After discharge at home other persons might receive 118 micro Sv. CONCLUSION:
      Our results, under very strict assumptions, clearly demonstrate that the
      calculated radiation exposure to medical and non medical personnel is well below
      the maximum annual dose limit. The use of any additional radiation protection
      device as syringe shielding does not significantly lower radiation exposure.

PMID- 14668960
TI  - Myocardial blood flow and coronary flow reserve in children with "normal"
      epicardial coronary arteries after the onset of Kawasaki disease assessed by
      positron emission tomography.
AB  - Myocardial blood flow (MBF) was investigated in children (14.2 +/- 5.01 years)
      with "resolved" coronary involvement after the onset of Kawasaki disease and
      angiographically normal epicardial coronary arteries. Ten asymptomatic children
      with a history of Kawasaki disease had electrocardiography, echocardiography, and
      positron emission tomography (PET) 10.3 +/- 6.01 years after onset of the acute
      illness. Myocardial perfusion was assessed by NH(3)- PET at rest and after
      vasodilatation and compared with that of 10 healthy volunteers (26.1 +/- 6.3
      years). No patient had signs of myocardial ischemia; on echocardiography
      ventricular function was normal without dyskinetic areas or signs of enlargement
      or stenosis of the proximal coronary arteries. There was no statistical
      significant difference between patients and volunteers in MBF at rest (0.86 +/-
      0.27 vs 0.77 +/- 0.17 ml/g/min), whereas MBF after vasodilatation (2.42 +/- 0.81
      vs 3.10 +/- 0.8 ml/g/min) and coronary flow reserve (CFR) (2.89 +/- 0.26 vs 4.09
      +/- 1.01 mmHg/ml/g/min) were significantly attenuated in the Kawasaki group. No
      stress-induced perfusion defects could be detected. In children with a history of
      Kawasaki disease and angiographically normal epicardial coronary arteries, there
      is a significant attenuation of MBF after vasodilatation and a significant
      reduction of CFR. Impairment of vasoreactive ability may indicate residual damage
      of the coronary arteries and may be a risk factor for atherosclerosis in
      adulthood.

PMID- 14668961
TI  - Predictors of successful transcatheter closure of atrial septal defect by cardiac
      magnetic resonance imaging.
AB  - The location, size, and rim of an atrial septal defect (ASD) are major
      determining factors for transcatheter closure. We compared the measurements of
      ASD size and the characteristics of atrial septal rim using cardiac magnetic
      resonance imaging (MRI) with those obtained using transesophageal
      echocardiography (TEE). Patients with an ASD that met established criteria were
      selected for evaluation by cardiac MRI and TEE. There were 66 patients who
      underwent both TEE and cardiac MRI. Bland-Altman comparative analysis was
      performed to demonstrate agreement between measurement of ASD by MRI and balloon
      sizing compared to measurement of ASD by TEE and balloon sizing. Twelve patients
      were excluded from transcatheter closure of ASD. TEE did not demonstrate an
      adequate measurement of the posterior inferior rim in 10 of 66 patients. Fifty
      four patients underwent transcatheter closure using the Amplatzer septal
      occluder. Of these, 52 patients had successful closure (ASD measurements of 25.9
      +/- 5.6 mm using MRI and 21.9 +/- 5.8 mm using TEE). The median device size was
      28 mm (range, 11-38). Patients who had successful closure had a significantly
      smaller major axis of ASD and larger posterior inferior rim compared to those of
      patients who were excluded from the closure procedure. Cardiac MRI showed a
      better correlation of ASD diameter measurement to balloon sizing compared to TEE.
      We believe that the most important predictive factor for successful transcatheter
      closure of an ASD is an adequate posterior inferior rim, which is best visualized
      using cardiac MRI.

PMID- 14668962
TI  - Pulmonary agenesis with congenital heart disease.
AB  - The combined anomalies of pulmonary agenesis and congenital heart disease are
      exceedingly rare and a highly lethal association. We describe four cardiovascular
      operations in three patients with this association. Open-heart surgery was
      performed in two patients, and palliative heart surgery was performed in two
      patients. One patient died 100 days after the operation because of severe
      tracheal stenosis and renal failure, but the other two patients are doing well.
      Surgical access through a thoracotomy, instead of a median approach, was adequate
      in all patients. Careful evaluation and a precise understanding of the anatomy
      are necessary for the surgical management of these patients.

PMID- 14668963
TI  - Enhanced coronary blood flow and abnormal blood flow in the aortic isthmus in
      severe fetal anemia.
AB  - Coronary arteries are not normally visualized by fetal echocardiograms. Reversal
      of flow in the transverse aortic arch is most often seen in association with
      severe coarctation. We describe a case of a near-term fetus whose fetal
      echocardiogram showed very prominent coronary arteries and severe reversal of
      flow in the transverse aorta suggestive of a coarctation who was postnatally
      confirmed to have normal intracardiac and aortic anatomy. We discuss the pitfalls
      in clinical diagnosis in this case to alert pediatric cardiologists of transient
      perturbations in physiology masquerading as heart disease.

PMID- 14668964
TI  - Concomitant occasional use of salbutamol influences bronchoprotective
      responsiveness afforded by formoterol in patients with the glycine-16 genotype.
AB  - BACKGROUND: Predisposition to subsensitivity with long-acting beta(2)-agonists
      (LABA) or regular short-acting beta(2)-agonists (SABA) is related to
      polymorphisms at codon 16 of the beta(2)-adrenoceptor. OBJECTIVE: To determine
      whether the use of occasional SABA induces further baseline downregulation of the
      beta(2)-adrenoceptor to that of endogenous catecholamines alone, in Gly-16
      patients. METHODS: A post-hoc analysis of two studies was performed. Twenty-three
      homozygous Gly-16 asthmatic patients received 12 microg inhaled formoterol either
      o.d. or b.i.d. for 2 weeks. Patients had been supplied with ipratropium bromide
      (IB) to use as reliever therapy preferentially over salbutamol. Spirometry and
      adenosine monophosphate (AMP) bronchial challenge was performed after 7-14 days
      of placebo and after active treatment. RESULTS: A review of domiciliary diary
      card data indicated 13 patients (mean FEV(1): 76.8% pred., AMP PC(20): 23.4
      mg/ml) did not require salbutamol, and 10 patients (mean FEV(1): 77.9% pred., AMP
      PC(20): 27.9 mg/ml) required occasional salbutamol (1.67 puffs/day) during run-in
      and/or formoterol periods. No significant difference in spirometry or AMP PC(20)
      were found between the populations after placebo. After formoterol, compared with
      placebo, patients requiring occasional salbutamol had no improvement in AMP
      PC(20) [geometric mean PC(20) (and 95% CI): 28.0 mg/ml (20.5-38.4) versus 34.46
      mg/ml (25.1-47.3)], while those patients not requiring salbutamol had a
      significant ( p<0.05) improvement in AMP PC(20) with formoterol compared with
      placebo [89.9 mg/ml (52.4-154.3) versus 30.6 mg/ml (17.8-52.5)]. This amounted to
      a 3.12-fold (95% CI: 0.16-6.07) geometric mean fold difference between groups.
      CONCLUSIONS: Our results indicate that homozygous Gly-16 patients using
      occasional salbutamol have reduced responsiveness to formoterol in terms of
      bronchoprotection to AMP than patients not using salbutamol. Patients expressing
      the homozygous gly-16 genotype of the beta(2)-adrenoceptor genotype receiving a
      LABA may benefit from the substitution of their usual SABA for an alternative
      reliever.

PMID- 14668965
TI  - Relationship between lipids and bone mass in 2 cohorts of healthy women and men.
AB  - A number of recent findings seem to indicate that fat and bone metabolism are
      strictly connected. We investigated the relationship between lipid profile and
      bone mineral density (BMD) in 236 either pre- or postmenopausal women, aged 35-81
      years, attending our osteoporosis center ("clinic group"). In order to verify the
      consistency of the results, 265 men and 481 women aged 68-75, participating in a
      population-based epidemiological investigation ("community cohort"), were also
      studied. Lumbar spine, femoral neck, total hip and total body BMD, total body
      fat, % fat mass and lean mass were measured using dual energy X-ray
      absorptiometry (DXA). In the clinic group, lumbar spine and hip BMD Z score
      values were both strongly related to all measured serum lipids: the relationship
      was negative for HDL cholesterol ( P < 0.05) and Apo A lipoprotein ( P < 0.000)
      and positive for LDL cholesterol ( P < 0.05), Apo B lipoprotein ( P < 0.001) and
      triglycerides ( P < 0.05). When BMD values were adjusted for body weight and BMI,
      most relationships remained statistically significant. In the community cohort,
      total body and hip BMD values were strongly related in both men and women to age,
      body weight, height, BMI, fat mass, lean mass, % fat mass. Total body and hip BMD
      were significantly related to serum lipids in both women and men. The
      relationship was negative for HDL cholesterol and positive for total cholesterol,
      triglycerides and LDL cholesterol. Most of these relationships (triglycerides,
      HDL cholesterol, LDL/HDL cholesterol ratio in women, and all measured lipids in
      men) remained statistically significant ( P values ranging from 0.000 to 0.03)
      when the BMD values were adjusted also for anthropometric measures (body weight,
      height, fat mass). This study demonstrates for the first time that the lipid
      profile is strictly related to bone mass in both men and women. The
      interpretation of this association remains hypothetical but it might open new
      perspectives for understanding the mechanisms controlling bone metabolism.

PMID- 14668966
TI  - Characterization of osteocalcin (BGP) and matrix Gla protein (MGP) fish specific
      antibodies: validation for immunodetection studies in lower vertebrates.
AB  - In fish species the basic mechanisms of bone development and bone remodeling are
      not fully understood. The classification of bone tissue in teleosts as cellular
      or acellular and the presence of transitional states between bone and cartilage
      and the finding of different types of cartilage in teleosts not previously
      recognized in higher vertebrates emphasizes the need for a study on the
      accumulation of the Gla-containing proteins MGP and BGP at the cellular level. In
      the present study, polyclonal antibodies developed against BGP and MGP from A.
      regius (a local marine teleost fish) and against MGP from G. galeus (a Pacific
      Ocean shark), were tested by Western blot for their specificity against BGP and
      MGP from several other species of teleost fish and shark. For this purpose we
      extracted and purified both proteins from various marine and freshwater teleosts,
      identified them by N-terminal amino acid sequence analysis and confirmed the
      presence of gamma-carboxylation in the proteins with the use of a stain specific
      for Gla residues. Each antibody recognized either BGP or MGP with no cross
      reaction between proteins detected. All purified fish BGPs and MGPs tested were
      shown to be specifically recognized, thus validating the use of these antibodies
      for further studies.

PMID- 14668967
TI  - An examination of triassic cynodont tooth enamel chemistry using fourier
      transform infrared spectroscopy.
AB  - The Cynodontia are considered to be particularly significant as their remains
      document the reptile-to-mammal transition during the Permian and Triassic
      periods. Studies examining cynodont morphology and anatomy have shown that these
      animals acquired increasingly mammal-like characteristics during their evolution.
      In this study, we use Fourier Transform Infrared spectroscopy to assess the
      enamel structure of several Triassic cynodonts. Extant Crocodylus niloticus and
      Varanus enamel spectra as well as published extant and fossil mammalian data were
      used as comparisons. The profiles of the cynodont spectra resemble biological
      apatite, in spite of their great age. The ratio of structural carbonate to
      phosphate in these cynodonts is significantly higher than in the extant and
      fossil mammals, but very similar to the extant reptiles. We suggest that the
      enamel apatite structure of these cynodonts was more similar to the reptilian
      rather than the mammalian pattern.

PMID- 14668968
TI  - Sensitive flow-injection chemiluminescence determination of terbutaline sulfate
      based on enhancement of the luminol-permanganate reaction.
AB  - A novel and highly sensitive chemiluminescence (CL) method for the determination
      of terbutaline sulfate, coupled with flow-injection analysis (FIA), is described
      in this paper. The method is based on enhancement by terbutaline sulfate of the
      chemiluminescence emission of the luminol-permanganate system under alkaline
      conditions. Under the conditions selected the concentration of terbutaline
      sulfate is proportional to CL intensity in the range 5 x 10(-10)-5 x 10(-7) g mL(
      1), with a detection limit of 1.7 x 10(-10) g mL(-1) (3 sigma). The relative
      standard deviation is 2.8% for 1 x 10(-8) g mL(-1) terbutaline sulfate ( n=11).
      Ninety samples can be determined per hour. The proposed method has been used to
      determine terbutaline sulfate in pharmaceutical preparations and in plasma and
      urine samples with satisfactory results. The possible mechanism of the
      chemiluminescence reaction is discussed briefly.

PMID- 14668970
TI  - Effects of 17 alpha-ethinylestradiol on zoo- and phytoplankton in lentic
      microcosms.
AB  - The effects of 17 alpha-ethinylestradiol (EE), an endocrine disruptor, on zoo-
      and phytoplankton were studied in outdoor 230-L still-water microcosms. Cell
      density and biomass, diversity, and community composition were analyzed. Five
      microcosms were treated by controlled release for six weeks, three by direct
      application of EE. To investigate recovery, sampling was continued for four weeks
      after treatment. Most characteristics of the zooplankton were not unambiguously
      affected by EE. Only the relative density of copepods, especially of their
      larvae, decreased significantly after EE application. For phytoplankton, no
      unambiguous concentration- or toxodose-correlated effects on any biotic
      characteristics could be found. However, most properties of the phytoplankton
      deviated from those of controls, i.e. tended to be smaller (number of species per
      microcosm, biomass, cell density) or covered a wider range (diversity, evenness).
      PCA indicated a shift of species structure in the treated microcosms. This was
      supported by the species scores calculated by the principal response curve
      method, although the principal response curve itself showed no clear EE
      correlated shifts. High variability within the biocenosis between microcosms and
      over time, probably because of disturbance of the ecosystem before starting of
      the test, might have superimposed EE-dependent effects.

PMID- 14668969
TI  - Characterization of peptide-protein interactions using photoaffinity labeling and
      LC/MS.
AB  - The combination of photoaffinity labeling (PAL) with modern mass spectrometric
      techniques is a powerful approach for the characterization of peptide-protein
      interactions. Depending on the analytical strategy applied, a PAL experiment can
      provide different levels of information ranging from the identification of
      interaction partners to the structural characterization of ligand-binding sites.
      On the basis of LC/MS data generated in the framework of the identification of
      the binding site of the neuropeptide corticotropin-releasing factor (CRF) on its
      binding protein (CRFBP), the key role of LC/MS in the characterization of
      photoadducts on different structural levels was demonstrated. Covalent
      photoadducts of rat CRFBP (rCRFBP) were obtained by PAL with different mono- and
      bifunctional benzophenone photoprobes designed on the basis of the sequence of
      the synthetic CRF fragment human/rat CRF(6-33) which binds to CRFBP with high
      affinity. In view of the stoichiometry, LC/MS analysis revealed that the
      photoadducts consisted of one molecule of photoprobe and one molecule of rCRFBP.
      For a further characterization of the photoadducts on the oligopeptide level,
      enzymatic digests of unlabeled rCRFBP and of the respective photoadduct were
      compared by peptide mapping monitored with LC/MS. Thereby, it was found that the
      photoprobe that contained the photophore at its N-terminus labeled the amino acid
      sequence rCRFBP(34-38), whereas the photoprobe that contained the photophore at
      its C-terminus labeled rCRFBP(12-26). On the basis of the characterization of the
      photoadduct formed by rCRFBP and the bifunctional photoprobe that contained
      photophores on both termini, semiquantitative comparison of different enzymatic
      digests was accomplished by application of the mass-selective multiple ion
      chromatogram strategy.

PMID- 14668971
TI  - A simple and robust set-up for on-column sample preconcentration--nano-liquid
      chromatography--electrospray ionization mass spectrometry for the analysis of N
      acylhomoserine lactones.
AB  - A simple method for the simultaneous, rapid and sensitive determination of N
      acylhomoserine lactone signaling molecules in bacterial isolates, without prior
      sample preconcentration and with minimal sample cleanup, is presented. The
      analysis relies on the combination of analyte preconcentration and separation on
      a single device: a relatively large sample volume (1-5 microL) is directly loaded
      onto a laboratory-made, miniaturized (75 microm i. d.) reverse phase nano-liquid
      chromatography column, connected on-line to a microelectrospray-ionization ion
      trap mass spectrometer. In a first step the analyte is adsorbed (and so
      concentrated) at the beginning of the column, and is eluted and selectively
      separated in a second step by the organic mobile phase. Sample preconcentration
      follows the mechanisms of solid phase extraction on a nano-scale, while
      separation takes place according to classical liquid chromatography separation
      principles. The columns can be manufactured easily, are simply connected, and
      used with minimal solvent amounts; this makes this method extremely robust and
      cost-effective. The analytical setup was found to be routinely quantitative down
      to a concentration of 10 ng/mL (corresponding to a total analyte amount of 10 pg
      or ca. 50 fmol). The limit of detection was reached at 1 ng/mL (1 pg, ca. 5
      fmol). Compared to the classical AHL analysis of bacterial cultures with
      biosensors, where selectivity and sensitivity is often limited, this rapid
      analytical technique is a substantial qualitative and quantitative improvement.
      Two unsubstituted N-acylhomoserine lactones could be identified and quantified
      from a Burkholderia cepacia culture supernatant in a chloroform extract.

PMID- 14668972
TI  - Trace determination of peptides in water samples using packed capillary liquid
      chromatography with UV and MS detection and characterization of peptide oxidation
      products by MS.
AB  - A capillary liquid chromatographic column switching method has been developed for
      fast and sensitive determination of peptides in water samples. Sample volumes of
      1 mL were loaded onto a (320 microm I.D. x30 mm) 10 microm Kromasil C(18) pre
      column, providing on-line analyte enrichment, prior to back-flushed elution onto
      a (320 microm I.D. x150 mm) 3.5 microm Kromasil C(18) analytical column. Loading
      flow rates of 250 microL/min and a mobile phase composition of
      acetonitrile/water/trifluoroacetic acid (22/77.9/0.1, v/v) provided a total
      analysis time of less than 25 minutes for the test peptides angiotensin II,
      bombesin, bradykinin, corazonin, neurotensin and substance P, using temperature
      programmed elution. In addition, solvent gradient elution and combined solvent
      gradient elution and temperature programming were explored. Using on-capillary UV
      detection at 210 nm resulted in a concentration limit of detection (cLOD) of
      about 1 ng/mL. The method was validated over the concentration range 1-100 ng/mL,
      yielding a coefficient of correlation of 0.997 or better. The within-assay ( n=6)
      and between-assay ( n=6) precisions of peak areas were on average 6% RSD and 5%
      RSD, respectively. When the method was applied to spiked chlorinated tap water
      samples, it was found that peptides containing methionine, tryptophan and cystine
      were oxidized. Identification of the oxidation products of the peptides in
      hypochlorite-treated water was done with positive electrospray ionization time-of
      flight mass spectrometric detection.

PMID- 14668973
TI  - A meta-analysis of the response to chronic L-dopa in patients with schizophrenia:
      therapeutic and heuristic implications.
AB  - RATIONALE: While it is generally believed that administration of the dopamine
      precursor levodopa ( L-dopa) exacerbates symptoms of schizophrenia, numerous
      reports suggest that adjunctive L-dopa may be beneficial. This body of literature
      has not been critically reviewed. OBJECTIVES: On the basis of published studies,
      to determine whether L-dopa administered concomitantly with antipsychotic drugs
      provides a beneficial response in patients with schizophrenia. METHODS: This
      review examined 30 studies involving 716 patients. Due to wide methodological
      variability and limited statistical information, only five studies encompassing
      160 patients could be included in a meta-analysis. The others were evaluated
      qualitatively. RESULTS: When L-dopa was added to antipsychotic drugs, the overall
      improvement was moderate ( d=0.71) and highly significant ( P<0.0001). There were
      16 other studies in which L-dopa was added to antipsychotic drugs, but which did
      not meet criteria for inclusion in the meta-analysis. In these, worsening
      occurred in less than 20% of patients; the percentage of improved patients varied
      widely but had a central tendency around 50%. CONCLUSIONS: . In patients already
      on antipsychotic drugs, the addition of L-dopa can be beneficial. Dopamine
      agonists merit further consideration as adjuncts to antipsychotic drugs in the
      treatment of schizophrenia.

PMID- 14668974
TI  - Patterns of functional activity associated with cocaine self-administration in
      the rat change over time.
AB  - RATIONALE: Although imaging studies in human addicts have been valuable for
      identifying the neural substrates of the effects of abused drugs, few studies
      have used this approach in animal models where conditions can be carefully
      controlled. OBJECTIVE: To define the substrates that mediate the effects of
      cocaine in a rodent model of cocaine self-administration using the 2
      [(14)C]deoxyglucose method and to assess changes in these patterns over the
      course of drug exposure. METHODS: Male Sprague-Dawley rats self-administered
      cocaine (0.75 mg/kg per injection; FR2; 21 injections/session) and control rats
      received saline infusions in the same pattern as the cocaine rats for 5 or 30
      days. Metabolic mapping was applied immediately after the final session. RESULTS:
      Following 5 days of self-administration, rates of glucose utilization were
      decreased in the nucleus accumbens, and increased in autonomic brainstem
      structures and in sensorimotor regions. After 30 days of cocaine exposure, self
      administration reduced glucose utilization throughout the dorsal and ventral
      striatum, central nucleus of the amygdala, medial forebrain bundle, and
      infralimbic and prelimbic prefrontal cortices. In addition, at this time point
      glucose utilization was no longer elevated in any autonomic or sensorimotor brain
      regions. CONCLUSIONS: These data demonstrate that the distribution of functional
      activity associated with self-administered cocaine undergoes considerable change
      over the course of drug exposure. While increases in metabolic rates were largely
      found in autonomic and sensorimotor structures after short-term cocaine access,
      decreases were prominent in mesocorticolimbic regions after prolonged exposure.
      These differences in the patterns of brain activity that develop with long-term
      cocaine self-administration may play a role in the transition to habitual drug
      seeking behavior.

PMID- 14668975
TI  - Effects of nicotine chewing gum on a real-life motor task: a kinematic analysis
      of handwriting movements in smokers and non-smokers.
AB  - RATIONALE: In laboratory tasks nicotine has consistently been shown to improve
      psychomotor performance. OBJECTIVES: The aim of the present experiment was to
      assess the effects of nicotine on a skilled task of everyday life in smoking and
      non-smoking healthy adults. METHODS: Assessment of handwriting movements of 38
      non-deprived smokers and 38 non-smokers was performed following the chewing of
      gum containing 0 mg, 2 mg or 4 mg of nicotine. A digitising tablet was used for
      the assessment of fine motor movements. Subjects were asked to perform a simple
      writing task. Movement time, velocity and acceleration of the handwriting
      movements were measured. Furthermore, every writing specimen was independently
      rated by two examiners regarding the quality of handwriting. RESULTS: Kinematic
      analysis of writing movements revealed that nicotine could produce absolute
      improvements in handwriting. Following nicotine administration, reduced movement
      times, increased velocities and more fluent handwriting movements were observed.
      These improvements were more striking in smokers than in non-smokers. No effects
      of nicotine were found with regard to the quality of handwriting. CONCLUSION: The
      results suggest that nicotine can enhance psychomotor performance to a
      significant degree in a real-life motor task.

PMID- 14668976
TI  - Ability of dopamine antagonists to inhibit the locomotor effects of cocaine in
      sensitized and non-sensitized C57BL/6 mice depends on the challenge dose.
AB  - RATIONALE: Studies in rats examining the ability of selective dopamine D(2)
      receptor class antagonists to attenuate the effects of a cocaine challenge have
      suggested that these agents are less potent in attenuating sensitized as opposed
      to non-sensitized locomotion. A potential issue with these studies is that the
      same challenge dose is used in sensitized and control conditions even though that
      dose may occupy different positions on the respective dose-response curves.
      OBJECTIVES: To examine whether the ability of dopamine antagonists to attenuate
      cocaine-induced locomotion differs between sensitized and non-sensitized animals
      if they are challenged with the same dose of cocaine, and with the lowest dose to
      maximally increase locomotion, which is lower in sensitized than in non
      sensitized animals. METHODS: Mice were treated repeatedly with 20 mg/kg cocaine
      or saline (for 3 consecutive days) and then challenged (after an 11-day drug-free
      interval) with different challenge doses of cocaine after pretreatment with a
      dopamine antagonist or saline. RESULTS: Using the same challenge dose of cocaine
      in both repeated treatment conditions (i.e. 20 mg/kg), the D(2 )class antagonists
      eticlopride and raclopride were less potent in attenuating the locomotor effects
      of cocaine in sensitized than those in non-sensitized animals. In contrast, when
      the lowest doses to maximally increase locomotion in each of the repeated
      treatment conditions were used (10 and 40 mg/kg), the D(2 )class antagonists
      attenuated the locomotor effects of cocaine in sensitized and non-sensitized
      animals with similar potencies. The ability of the D(1) class antagonist SCH23390
      to attenuate the effects of cocaine demonstrated a similar dependency on the
      challenge dose. CONCLUSIONS: These results show that, under the present
      conditions, the ability of dopamine antagonists to attenuate cocaine-induced
      locomotion is similar in sensitized and non-sensitized animals when challenged
      with pharmacologically equivalent doses of cocaine, but not when challenged with
      the same dose.

PMID- 14668977
TI  - The opioid antagonist naltrexone reduces the reinforcing effects of Delta 9
      tetrahydrocannabinol (THC) in squirrel monkeys.
AB  - RATIONALE: Experimental evidence from animal studies suggests reciprocal
      functional interactions between endogenous brain cannabinoid and opioid systems.
      There is recent evidence for a role of the opioid system in the modulation of the
      reinforcing effects of synthetic cannabinoid CB1 receptor agonists in rodents.
      Since Delta(9)-tetrahydrocannabinol (THC), the natural psychoactive ingredient in
      marijuana, is actively and persistently self-administered by squirrel monkeys,
      this provides an opportunity to directly study involvement of opioid systems in
      the reinforcing effects of THC in non-human primates. OBJECTIVES: To study the
      effects of naltrexone, an opioid antagonist, on THC self-administration behavior
      in squirrel monkeys. METHODS: Monkeys pressed a lever for intravenous injections
      of THC under a ten-response, fixed-ratio (FR) schedule with a 60-s time-out after
      each injection. Effects of pre-session treatment with naltrexone (0.03-0.3 mg/kg
      intramuscularly, 15 min before session) for 5 consecutive days on self
      administration of different doses of THC (2-8 microg/kg per injection) were
      studied. RESULTS: Self-administration responding for THC was significantly
      reduced by pretreatment with 0.1 mg/kg naltrexone for five consecutive daily
      sessions. Naltrexone pretreatment had no significant effect on cocaine self
      administration responding under identical conditions. CONCLUSIONS: Self
      administration behavior under a fixed-ratio schedule of intravenous THC injection
      was markedly reduced by daily pre-session treatment with naltrexone, but remained
      above saline self-administration levels. These findings demonstrate for the first
      time the modulation of the reinforcing effects of THC by an opioid antagonist in
      a non-human primate model of marijuana abuse.

PMID- 14668978
TI  - In vitro vasodilator mechanisms of the indole alkaloids rhynchophylline and
      isorhynchophylline, isolated from the hook of Uncaria rhynchophylla (Miquel).
AB  - Rhynchophylline (Rhy) and isorhynchophylline (Isorhy), indole alkaloids from
      Uncaria hooks, reportedly exert hypotensive and vasodilatory effects, but the
      mechanism of action is unclear. We therefore investigated the relaxant effects of
      these two isomeric alkaloids in rat arteries in vitro, in particular in respect
      of the various functional Ca2+ pathways. Both Rhy and Isorhy relaxed aortic rings
      precontracted with phenylephrine (PE, 1 microM) in a dose-dependent manner (3-300
      microM). Removal of endothelium and preincubation with L-NAME (300 microM)
      slightly inhibited but did not prevent the relaxant response. These results
      indicate that Rhy and Isorhy act largely in an endothelium-independent manner.
      Unlike nicardipine, both alkaloids not only inhibited the contraction induced by
      60 mM KCl (IC50 20-30 microM), but also that induced by PE and U46619, albeit to
      a lesser extent (IC50 100 and 200 microM, respectively). These results suggest
      that Rhy and Isorhy may act via multiple Ca2+ pathways. In contrast to their
      inhibitory effects on KCl-induced and receptor-mediated contractions, where both
      isomers were comparably potent, Rhy was more potent than Isorhy at higher
      concentrations (>100 microM) in inhibiting both caffeine (25 mM)- and
      cyclopiazonic acid (CPA, 30 microM)-induced contractions. Similar results
      observed with caffeine in Ca2+-containing medium were also observed in Ca2+-free
      medium. However, 0.1-0.3 microM nicardipine (which completely inhibited KCl
      induced contraction) had no significant inhibitory effect on CPA-induced
      contractions. Taken together, these results indicate discrimination between these
      two isomers with respect to Ca2+-induced Ca2+ release and non-L-type Ca2+
      channel, but not for IP3-induced Ca2+ release and L-type Ca2+ channels. Similar
      relaxant responses to KCl- and caffeine-induced contractions were seen when these
      two alkaloids were tested on the smaller mesenteric and renal arteries. In
      conclusion, the vasodilatory effects of Rhy and Isorhy are largely endothelium
      independent and are mediated by L-type Ca2+ channels. At higher concentrations,
      they also affect other Ca2+-handling pathways, although to a lesser extent. While
      there is no discrimination between the two isomers with respect to the
      contraction induced by KCl or agonists (PE and U46619), differential effects
      between Rhy and Isorhy were seen on caffeine- and CPA-induced contractions.

PMID- 14668979
TI  - Molecular analysis of a subcellular compartment: the magnetosome membrane in
      Magnetospirillum gryphiswaldense.
AB  - The ability of magnetotactic bacteria (MTB) to orient and migrate along magnetic
      field lines is based on magnetosomes, which are membrane-enclosed intracellular
      crystals of a magnetic iron mineral. Magnetosome biomineralization is achieved by
      a process involving control over the accumulation of iron and deposition of the
      magnetic particle, which has a specific morphology, within a vesicle provided by
      the magnetosome membrane. In Magnetospirillum gryphiswaldense, the magnetosome
      membrane has a distinct biochemical composition and comprises a complex and
      specific subset of magnetosome membrane proteins (MMPs). Classes of MMPs include
      those with presumed function in magnetosome-directed uptake and binding of iron,
      nucleation of crystal growth, and the assembly of magnetosome membrane
      multiprotein complexes. Other MMPs comprise protein families of so far unknown
      function, which apparently are conserved between all other MTB. The mam and mms
      genes encode most of the MMPs and are clustered within several operons, which are
      part of a large, unstable genomic region constituting a putative magnetosome
      island. Current research is directed towards the biochemical and genetic analysis
      of MMP functions in magnetite biomineralization as well as their expression and
      localization during growth.

PMID- 14668981
TI  - [Diabetes mellitus and bladder function. What should be considered?].
AB  - Increasing prevalence of diabetes mellitus and rising patient life expectancy are
      causing an accumulation of urologic late complications-despite or due to steadily
      improving medical health care. The prevalence of diabetic cystopathy (impaired
      bladder sensation, increased bladder capacity, sometimes accompanied by voiding
      difficulties and residual urine) is 25% in non-insulin-dependent diabetics and
      48% in insulin-dependent diabetics. Autonomic and peripheral neuropathy lead to
      detrusor hyposensitivity, and chronic overstretching of the bladder causes
      myogenic detrusor hypocontractility. Since diabetic cystopathy often develops
      insidiously and asymptomatically, prevention of secondary complications such as
      recurrent urinary tract infections, vesicorenal reflux, nephrolithiasis, and
      pyelonephritis requires the urologist's full attention as well as early and
      repeated urodynamic diagnostics. Comorbidities can lead to a variety of
      urodynamic findings. Therapeutic options are generally conservative (timed
      voiding, micturition training, CIC, pharmacotherapy) and should be part of an
      integrated interdisciplinary health care approach since undiscovered
      complications involving non-urologic organ systems create a higher long-term
      socioeconomic burden than preventive support provided by other specialists.

PMID- 14668982
TI  - [Bladder dysfunction due to rare neurological disorders].
AB  - Diseases or lesions of the central or peripheral nervous system involving the
      innervation of the lower urinary tract lead to neurogenic bladder dysfunction.
      Results are typical changes in storage and voiding function of the bladder
      according to pathophysiological and urodynamical criteria. In case of
      neurological disorders the neurological symptoms are not always the leading ones.
      The differential diagnosis of correlating bladder dysfunction is often difficult
      and special pathophysiological knowledge is necessary. Etiological factors are
      congenital, degenerative, vascular, inflammatory and immunological processes or
      tumour-specific changes of the nervous system. In many cases urodynamic
      evaluation and early interdisciplinary cooperation is necessary for special
      differentiation and diagnosis, especially of those diseases which rarely lead to
      initial bladder symptoms. The "nonneurogenic neurogenic bladder" or "Hinman
      Syndrom" is well known in the literature but shouldn't be diagnosed until
      possible neurological reasons are excluded by modern diagnostic tools with newest
      imaging techniques.

PMID- 14668983
TI  - [Bladder dysfunction and surgery in the small pelvis. Therapeutic possibilities].
AB  - The more extensive a surgical procedure in a small pelvis, the higher the risk
      for the lower urinary tract with its nerve supply and nerve plexus. This concerns
      mainly the sympathetic chains, the parasympathetic structures and, rarely, the
      visceral supply of the pelvic floor. Direct trauma to the bladder and its
      vascular supply as well as indirect injury by displacement of the bladder need to
      be seriously considered. Problems with micturition and impaired storage capacity
      of the bladder are the result. Complete urodynamic examination and follow-up can
      help in differentiating between temporary and persisting disturbances and in
      taking therapeutical decisions. The most evident postoperative complication is
      disturbed micturition, managed initially by suprapubic urinary diversion,
      followed as soon as possible by intermittent self-catheterisation. This is the
      only way to avoid overstretching of the bladder, recurring urinary tract
      infection and damage to the upper urinary tract. Restoration of spontaneous
      micturition can be supported by drug treatment with parasympatholytics and/or
      alpha-blockers if the measured bladder pressure and residual urine are within
      tolerable limits. For electrostimulation of micturition, intravesical therapy,
      although timeconsuming, is best suited because it can easily be done on an
      outpatient basis. More promising seems bilateral sacral neuromodulation, which,
      however, is a rather complicated and expensive procedure. Surgical procedures to
      reduce the voiding resistance of the bladder involve the risk of postoperative
      incontinence because the sphincter function in those patients is often disturbed
      too. Persisting problems with bladder storage capacity as a result of tumor
      surgery in the small pelvis are frequently secondary to retention of urine
      (overflow incontinence). In these cases, regular evacuation of the bladder by
      intermittent self-catheterisation can lead to social acceptance. Reduced bladder
      compliance and lowering of the urethral leak pressure point may result in stress
      and urge incontinence, which, according to the established rules, should be
      managed by physiotherapy and behaviour therapy as well as drug therapy and only
      in exceptional cases by surgical measures. Prevention of postoperative bladder
      dysfunction can be tried by tissue- and nerve-sparing surgical techniques, but is
      always determined by oncological aspects.

PMID- 14668984
TI  - [Bladder dysfunction due to spinal cord compression. Treatment modes and
      results].
AB  - Bladder dysfunction is often observed in cases of spinal compression and is
      commonly caused by spinal tumors, trauma, or degenerative spine disease.
      Microsurgical decompression is the most important therapy. The earlier
      microsurgery is performed, the better the chances are for recovery of bladder
      function.

PMID- 14668985
TI  - [Bladder disorders in dementia and Alzheimer's disease. Rational diagnostic and
      therapeutic options].
AB  - In addition to cognitive failures, urinary incontinence is the central symptom in
      patients with demential syndromes. Cerebral atrophic processes with loss of
      cerebral bladder control result in the typical uninhibited bladder with urge
      syndrome and urge incontinence. In principle, all diagnostic and therapeutic
      options are available for those patients. However, the extent and invasivity of
      diagnostic as well as therapeutic procedures should individually be adapted to
      the patient's symptoms, age, physical and mental status. In most of the cases,
      non-invasive diagnostic procedures, with the bladder diary as the central
      diagnostic tool, are able to classify the bladder disorder. The patient's
      capability of active cooperation to the therapy and the prerequisites in nursing
      support determine the therapeutic strategies which are above all pharmacological
      relaxation of the detrusor, continence training programmes including behavioural
      modification and optimizing the patient's supply with pads. In most of the cases
      complete continence cannot be achieved. Therefore the primary aim of the therapy
      in patients with demential syndromes must be the guarantee of social continence
      which allows the patient an integration in his social environment.

PMID- 14668986
TI  - [The medication-induced dysfunction of the urinary bladder].
AB  - Bladder dysfunction can result from pathological changes in the bladder itself,
      of its central neurological regulation, (BPS), or of non-urological diseases such
      as diabetes or heart failure. Medication-induced bladder dysfunction can mostly
      be treated by simple changes in the pharmacological therapy. Bladder dysfunction
      can be induced pharmacologically by activating or inhibitory influences on
      adrenergic, sympathetic, beta-receptor-induced relaxation of the detrusor, alpha
      receptor-induced contraction of the bladder neck, or cholinergic,
      parasympathetic, muscarinic receptor-induced contraction of the detrusor.
      Diuretics can increase urine production, thus possibly leading to incontinence.
      If incontinence occurs in patients, treatment should be stopped if possible and
      additional pharmacological therapy should not be started before medication
      induced bladder dysfunction is excluded.

PMID- 14668987
TI  - [New insights into the role of estogens and their receptors in prostate cancer].
AB  - The present review gives a survey on the differential expression of estrogen
      receptors alpha and beta (ERalpha, ERbeta) and the progesterone receptor (PR) in
      human prostate tissue and discusses their potential implications for normal and
      abnormal prostatic growth. The differentiation compartment of the prostatic
      epithelium (secretory luminal cells) expresses high levels of ERbeta, while the
      ERalpha is restricted to the proliferation compartment (basal cells). In high
      grade prostatic intraepithelial neoplasia (HGPIN), ERalpha gene expression
      extends to luminal cells and thus may mediate cancerogenic effects of estrogens
      on the dysplastic epithelium. Conversely, the ERbeta is downregulated in HGPIN
      indicating that the chemopreventive effects of phytoestrogens mediated by the
      ERbeta are partially lost. Irrespective of grades and stages, prostate cancer
      retains high levels of the ERbeta, which is partially lost in androgen
      insensitive stages of the disease. In contrast with breast cancer, the presence
      of the ERalpha and the progesterone receptor (PR) is a late event in prostate
      cancer progression. At least 30% of metastatic and androgen-insensitive tumors
      express high levels of the PR indicating that these tumors harbor a functional
      ERalpha. The antiestrogen raloxifene has growth-inhibitory effects on androgen
      insensitive prostate cancer cells in vitro and induces apoptotic cell death in a
      dose-dependent fashion. These data provide a rationale for clinical trials to
      study the efficiency of antiestrogens in the medical treatment of advanced
      prostate cancer.

PMID- 14668988
TI  - [Misdiagnosis of urinalysis due to in vivo formation of urinary stones].
AB  - The occurrence of biochemically unaltered urinalyses in patients with severe
      recurrent stone formation is not a rare observation in practice. The possible
      reasons for that phenomenon are manifold. We show that stone growth-related
      urinary depletion of lithogenic constituents caused by acute growth of urinary
      calculi in vivo can be an important reason for the observed phenomenon. The
      described process which can strongly influence the urinary composition occurs in
      any stone-bearing patient. Thus, it is strongly recommended that stone-related
      alterations be taken into account when interpreting the urinalyses of these
      patients. Based on simplified model assumptions, the extent of the expected
      chemical depletion effect can be calculated for any stone patient's urine sample.
      In two easy-to-use nomograms, we have combined the key parameters which govern
      the process, allowing the user a fast and easy estimation.

PMID- 14668989
TI  - [Bilateral testicular masses in the scope of adrenogenital syndrome].
AB  - Testicular masses in male individuals with the adrenogenital syndrome (AGS) are a
      clinical and pathological diagnostic dilemma. The major differential diagnosis of
      gonadal nodules in this setting includes interstitial Leydig cell tumors and
      secondary benign tumors possibly of adrenal origin. We report a case of
      adrenogenital syndrome occurring in a 14-year-old boy. Examinations to clarify
      the cause of his dwarfism and bilateral testicular masses revealed 21-hydroxylase
      deficiency. The testes were not tender and were firm and nodular on palpation.
      The serum levels of adrenocorticotrophic hormone (ACTH), 17 alpha
      hydroxyprogesterone (17-alpha-OHP), testosterone, and aldosterone were found to
      be elevated. Under corticosteroid therapy the serum marker abnormalities were
      corrected and there was gradual regression of the tumor lesions in both testes.
      Testicular tumors with adrenogenital syndrome are typically bilateral and develop
      in untreated or inadequately treated males with AGS.

PMID- 14668990
TI  - [Acute meningitis after transrectal prostate biopsy].
AB  - Acute meningitis caused by Escherichia coli is a rare disease in adulthood.
      Medical procedures, e.g. surgical interventions, have been described as a cause.
      Infection by blood transmission of fecal E. coli is also known. We report a case
      of acute meningitis after transrectal prostate biopsy. E. coli could be
      identified both in the cerebrospinal fluid and in the blood culture. A broad
      initial antibiotic therapy was administered. After cultural isolation of E. coli
      the therapy was switched to cefotaxime. The initially comatose patient recovered
      swiftly.

PMID- 14668991
TI  - [Morphology and functional anatomy of the growing thorax].
AB  - Morphogenesis of most thoracic organs and structures is not finished with birth
      but perpetuates in postnatal life. The postnatal growth is partly associated with
      enormous changes in structure, morphology, and function. Our study presents an
      overview of morphological, topological and functional peculiarities of thoracic
      anatomy during infancy, childhood and adolescence. It focuses on the development
      of the mammary gland, osseous structures of the chest wall, thymus, heart, and
      lungs. Most of the presented data are based on post-mortem studies. Measurements
      and numerical data are mainly included for illustration of growth-associated
      changes.

PMID- 14668992
TI  - [Digital radiography of the chest in pediatric patients].
AB  - The hopes placed in digital radiography have been fulfilled only partly in
      pediatric radiology. Specifically, the option of gaining reduced radiation
      exposure in combination with a similar or even improved image quality was hard to
      realize. The only portable digital system available for a long time were storage
      phosphors which were disadvantaged by an extremely limited dose-quantum
      efficiency (DQE) in comparison to digital flat panel detectors. New developments
      and the introduction of the dual-reading system led to image qualities comparable
      to film-screen-systems with high resolution and achievable without dose increase,
      sometimes even with dose reduction. A study using an animal model suggests that
      these systems can even be used in preterm infants with very low birth weights. A
      new portable flat panel detector by Canon may improve digital chest radiography
      in pediatric patients.

PMID- 14668993
TI  - [Low dose multislice CT in the pediatric patient].
AB  - In the past years, multislice CT (MS-CT) has become an important diagnostic
      modality for the radiological evaluation of the thorax in children and
      adolescents. However, the higher stochastic radiation risks in pediatric
      patients, as compared to adults, necessitate a prudent use of MS-CT. This article
      presents an overview of the benefits of multislice CT and a variety of
      possibilities for radiation reduction in pediatric patients of different ages.

PMID- 14668994
TI  - [3D cross section of the laryngotracheal tract. A new method for visualization
      and quantification of tracheal stenoses].
AB  - PURPOSE: Demonstration of a technique for 3D assessment of tracheal stenoses,
      regarding site, length and degree, based on spiral computed tomography (S-CT).
      PATIENTS AND METHODS: S-CT scanning and automated segmentation of the laryngo
      tracheal tract (LTT) was followed by the extraction of the LTT medial axis using
      a skeletonisation algorithm. Orthogonal to the medial axis the LTT 3D cross
      sectional profile was computed and presented as line charts, where degree and
      length were obtained. Values for both parameters were compared between 36
      patients and 18 normal controls separately. Accuracy and precision was derived
      from 17 phantom studies. RESULTS: Average degree and length of tracheal stenoses
      were found to be 60.5% and 4.32 cm in patients compared to minor caliber changes
      of 8.8% and 2.31 cm in normal controls (p <0.005). For the phantoms an excellent
      correlation between the true and computed 3D cross sectional profile was found (p
      <0.005) and an accuracy for length and degree measurements of 2.14 mm and 2.53%
      respectively could be determined. The corresponding figures for the precision
      were found to be 0.92 mm and 2.56%. CONCLUSION: LTT 3D cross sectional profiles
      permit objective, accurate and precise assessment of LTT caliber changes. Minor
      LTT caliber changes can be observed even in normals and, in case of an otherwise
      normal S-CT study, can be regarded as artefacts.

PMID- 14668995
TI  - [High-resolution computed tomography (HRCT) of the pediatric lung].
AB  - High-resolution computed tomography (HRCT) of the lung is a very valuable method
      in the evaluation of children with acute and chronic lung disease due to the high
      spatial resolution and precise display of anatomy and pathology without
      superposition. The following publication will describe an optimized HRCT
      technique in order to reduce dose, explain various HRCT pattern and explain
      typical pediatric lung diseases.

PMID- 14668996
TI  - [Thoracic sonography in infancy and childhood].
AB  - Thoracic sonography has become an established imaging tool for evaluating
      specific paediatric thoracic diseases; particularly queries such as thymomegaly,
      pleural effusion, pulmonal sequester or thoracic small part pathology may be
      reliably addressed. Using appropriate ultrasound equipment the well trained and
      experienced investigator may diagnose these conditions without the need for a
      radiating imaging modality or help to evaluate equivocal findings on chest plain
      films. The important requisites as well as the established disease entities that
      pose an indication for thoracic ultrasound are listed and described. The
      restrictions and setbacks are discussed, and an algorithm for additional imaging
      and typical scenarios is supposed in order to help and encourage the meaningful
      and efficient use of this non-ionising, easy applicable imaging tool to chest
      queries. In conclusion, this review tries to give an overview of the restrictions
      and indications for thoracic sonography in neonates, infants and children as a
      useful imaging tool when indicated.

PMID- 14668997
TI  - [Radiomorphology of inflammatory lung diseases in childhood].
AB  - Imaging plays an important role in the diagnosis and therapy of children with
      suspected pulmonary infections. The role consists in confirmation or exclusion of
      pneumonia, differentiation between the entities, exclusion of other causes and
      evaluation of related complications.

PMID- 14668998
TI  - [Benign and malignant pulmonary tumors in childhood].
AB  - Pulmonary tumors in children are rare. Nevertheless, there are besides malign
      primary neoplasms and metastases also some benign tumors that the radiologist
      should know. The identification of some tumors is difficult, since some of them
      may mimic pulmonary inflammation. The first diagnostic tool is chest radiography.
      After that, a CT with contrast medium should be performed, if possible a
      multislice-CT (MSCT). Identification of mediastinal structures is best with MRI.

PMID- 14668999
TI  - [Thoracic findings in pediatric patients with cystic fibrosis].
AB  - Cystic fibrosis is the most common autosomal recessive metabolic disease in
      Europe with an incidence of 1:2500. The severity of the lung disease is the most
      important factor of morbidity and mortality in CF-patients. Because of the better
      diagnostic and therapeutic modalities life expectancy has increased
      significantly. The underlying pathology is a defect of chromosome 7, which
      encodes the regulation of the fluid balance across the cell membrane which
      effects chloride as well as sodium. The exocrine glands produce a viscous mucus
      which obstructs the airways and promotes infections. The result is the
      destruction of lung parenchyma. In daily routine, chest x-ray is still the most
      important radiological tool, although computed tomography depicts changes in
      morphology earlier and more exactly. Recent research studies show that MRI has
      because of its additional functional options-interesting aspects for the future.

PMID- 14669000
TI  - [Bilateral acoustic neurinoma].

PMID- 14669003
TI  - The effect of food abundance on territory size and population density of juvenile
      steelhead trout (Oncorhynchus mykiss).
AB  - Optimal territory size models predict a decrease in territory size with
      increasing food abundance. However, most of these models may not be applicable to
      juvenile salmonids in streams, because they defend contiguous territories at high
      densities. The optimal size of a contiguous territory is predicted to (1) be
      independent of food abundance when food is rare and (2) decrease only when food
      abundance is high enough to induce a reduction in territory size below the
      contiguous optimum. To test these predictions, we raised equal densities of
      juvenile steelhead trout in outdoor stream channels over a 32-fold range of food
      abundance in the absence of emigration for 25 days. Increasing competition for
      scarce food resulted in increasing mortality, higher willingness to emigrate,
      higher variance in body mass, lower growth, lower population density and lower
      biomass. The size of territories decreased with increasing local population
      density, and increased with increasing body size. However, territory size did not
      change with food abundance, a result consistent with the prediction of a
      contiguous territory size model. On average, total salmonid biomass increased 5.7
      times in response to the 32-fold increase in food abundance. Our data provide
      strong support for an earlier quantitative relationship between the abundance of
      stream salmonids and their food.

PMID- 14669002
TI  - Release of active and depot GDF-5 after adenovirus-mediated overexpression
      stimulates rabbit and human intervertebral disc cells.
AB  - To develop new therapeutic options for the treatment of disc degeneration we
      tested the possibility of overexpression of active growth and differentiation
      factor (GDF) 5 and of transforming growth factor (TGF) beta(1) by adenoviral gene
      transfer and characterized its effect on cell proliferation and matrix synthesis
      of cultured rabbit and human intervertebral disc cells. Recombinant adenovirus
      encoding for GDF-5 or TGF-beta(1) was developed and transgene expression
      characterized by RT-PCR, western blot and ELISA. Growth and matrix synthesis of
      transduced cells was measured by [(3)H]thymidine or [(35)S]sulfate incorporation.
      Disc cells expressed the receptors BMPR1A, BMPR1B, and BMPR2, which are relevant
      for GDF-5 action. Adenovirus efficiently transferred the GDF-5 gene or the TGF
      beta(1) gene to rabbit and human intervertebral disc cells. About 50 ng GDF-5
      protein/10(6 )cells per 24 h or 7 ng TGF-beta(1) protein/10(6 )cells per 24 h was
      produced. According to western blotting, two GDF-5 forms, with molecular weights
      consistent with the activated GDF-5 dimer and the proform, were secreted over the
      3 weeks following gene transfer. Overexpressed GDF-5 and TGF-beta(1) were
      bioactive and promoted growth of rabbit disc cells in monolayer culture. Our
      results suggest that ex vivo gene delivery of GDF-5 and TGF-beta(1) is an
      attractive approach for the release of mature and pre-GDF-5 in surrounding
      tissue. This leads us to hope that it will prove possible to improve the
      treatment of degenerative disc disease by means of ex vivo gene transfer of
      single or multiple growth factors.

PMID- 14669001
TI  - Leukocyte recruitment and acute renal failure.
AB  - Despite advances in medical technology, acute renal failure (ARF) still
      represents a major challenge in clinical medicine, as morbidity and mortality
      have remained unchanged over the past two decades. The pathophysiology of ARF is
      highly complex and only poorly understood; new insights into the pathophysiology
      of ARF are therefore of utmost importance to develop better understanding and
      therapies. Acute tubular necrosis (ATN) is the predominant cause of ARF and often
      arises as a consequence of septic, toxic, or ischemic insults. The recruitment of
      leukocytes into the kidney has recently emerged as a key event in the development
      of experimental ischemic and septic ARF. A few descriptive clinical studies
      support this idea. However, the clinical relevance of various animal models
      remains unclear, as does the importance of different leukocyte subsets, and even
      methodological aspects as how to quantify renal leukocyte recruitment. This
      review summarizes and critically evaluates experimental findings that provide
      insight into the role of leukocytes and their recruitment during ARF. We aim to
      provide a valid description of ARF, illustrate animal models of ARF, review
      qualitative and quantitative methods to assess renal leukocyte recruitment, and
      discuss the components of the leukocyte recruitment cascade and their role in
      ARF.

PMID- 14669004
TI  - The effect of mean and variance in resource supply on survival of annuals from
      Mediterranean and desert environments.
AB  - Resource availability is often characterized by mean annual amounts, while
      ignoring the spatial variation within habitats and the temporal variation within
      a year. Yet, temporal and spatial variation may be especially important for
      identifying the source of stress in low productivity environments such as deserts
      where resources are often pulsed and resource renewal events are separated by
      long periods of low resource availability. Therefore, the degree of stress will
      be determined in part by the length of time between recharge events. Here, we
      investigated the effect of timing and total amount of water application on two
      congeneric pairs, each with a population from a low (desert) and a high
      (Mediterranean) productivity habitat. As expected, highest survival and greatest
      growth were found at low or intermediate recharge intervals, and the magnitude of
      response to increases in total seasonal amounts was greater for Mediterranean
      species than desert species. The species that had greater survival switched in
      the hierarchy under high total water depending on interval length. These results
      demonstrate that temporal variation in resource availability can be as important
      as annual total amounts for plant performance and that response to temporal
      dynamics can vary between species. This has implications for community-level
      processes, as competitive hierarchies may switch based on resource dynamics
      rather than only total availability.

PMID- 14669005
TI  - Does pollination limit tolerance to browsing in Ipomopsis aggregata?
AB  - Ungulate browsing of flowering stalks of the semelparous herb Ipomopsis aggregata
      leads to regrowth of lateral inflorescences, a response that has been reported to
      yield overcompensation in some cases (browsed plants with higher reproductive
      success than unbrowsed), but undercompensation in others. Little is known about
      the mechanisms that cause such variable tolerance to herbivory. We explored one
      possible mechanism--variation in effects of browsing on pollination--by clipping
      I. aggregata inflorescences to mimic browsing, observing subsequent visits by
      pollinators and nectar-robbers, and adding pollen by hand to flowers of some
      clipped and unclipped plants. Clipping reduced floral display size and increased
      inflorescence branching, but neither hummingbirds, the primary pollinators, nor
      nectar-robbing bumblebees showed any preference for unclipped versus clipped
      plants. Clipping delayed flowering; this shift in phenology caused clipped plants
      to miss the peak of hummingbird activity and to have lower per-flower visitation
      rates than unclipped controls in one year, but to have greater overlap with birds
      and higher visitation rates in the subsequent year. In three sites and 2 years,
      clipped plants exposed to natural pollination suffered extreme undercompensation,
      producing on average only 16% as many seeds as unclipped controls. This was not
      directly attributable to clipping effects on pollination, however, because
      clipped plants were unable to increase fecundity when provided with supplemental
      pollen by hand. Taken altogether, our results suggest that compensation was
      constrained less by indirect effects of browsing on pollination than by its
      direct impacts on resource availability and hence on the ability of plants to
      regrow lost inflorescence tissue and to fill seeds. Exploring the physiological
      and developmental processes involved in regrowth of inflorescences and
      provisioning of seeds is a promising future direction for research designed to
      understand variation in browsing tolerance.

PMID- 14669006
TI  - Multiple disturbances accelerate invasion of reed canary grass (Phalaris
      arundinaceaL.) in a mesocosm study.
AB  - Disturbances that intensify with agriculture and/or urban development are thought
      to promote the spread of invasive plants, such as the clonal perennial reed
      canary grass (Phalaris arundinaceaL). To test this relationship and interactions
      among disturbances, we subjected wet prairie assemblages within 1.1 m(2)
      mesocosms to invasion by Phalaris and addition of nutrients, sediments, and
      flooding. Species richness decreased with the application of sediments and/or
      flooding of 4 consecutive weeks or longer. Losses of up to six dominant and
      subdominant species in these treatments increased light transmission through the
      plant canopy by as much as 400% over the control. Light availability in July and
      September was a strong predictor of end-of-season aboveground biomass of
      Phalaris. Phalaris was also 35% and 195% more productive when nutrients were
      added at low and high levels, respectively. Multiple factors in combination were
      usually additive in their effects on invasion, but sediments and nutrients
      interacted with flood regime to synergistically increase invasion in some cases.
      A separate experiment likewise revealed a synergistic interaction between added
      nutrients and simulated grazing. We suggest that multiple factors be mitigated
      simultaneously to reduce invasion of Phalaris.

PMID- 14669007
TI  - Precipitation pulse size effects on Sonoran Desert soil microbial crusts.
AB  - Deserts are characterized by low productivity and substantial unvegetated space,
      which is often covered by soil microbial crust communities. Microbial crusts are
      important for nitrogen fixation, soil stabilization and water infiltration, but
      their role in ecosystem production is not well understood. This study addresses
      the following questions: what are the CO2 exchange responses of crusts to pulses
      of water, does the contribution of crusts to ecosystem flux differ from the soil
      respiratory flux, and is this contribution pulse size dependent? Following water
      application to crusts and soils, CO2 exchange was measured and respiration was
      partitioned through mixing model analysis of Keeling plots across treatments.
      Following small precipitation pulse sizes, crusts contributed 80% of soil-level
      CO2 fluxes to the atmosphere. However, following a large pulse event, roots and
      soil microbes contributed nearly 100% of the soil-level flux. Rainfall events in
      southern Arizona are dominated by small pulse sizes, suggesting that crusts may
      frequently contribute to ecosystem production. Carbon cycle studies of arid land
      systems should consider crusts as important contributors because of their dynamic
      responses to different pulse sizes as compared to the remaining ecosystem
      components.

PMID- 14669011
TI  - Auditory system.

PMID- 14669009
TI  - Modulation of penetrance by the wild-type allele in dominantly inherited
      erythropoietic protoporphyria and acute hepatic porphyrias.
AB  - We have recently demonstrated that in an autosomal dominant porphyria,
      erythropoietic protoporphyria (EPP), the coinheritance of a ferrochelatase (FECH)
      gene defect and of a wild-type low-expressed FECH allele is generally involved in
      the clinical expression of EPP. This mechanism may provide a model for phenotype
      modulation by minor variations in the expression of the wild-type allele in the
      other three autosomal dominant porphyrias that exhibit incomplete penetrance:
      acute intermittent porphyria (AIP), variegata porphyria (VP) and hereditary
      coproporphyria (HC), which are caused by partial deficiencies of hydroxy-methyl
      bilane synthase (HMBS), protoporphyrinogen oxidase (PPOX) and coproporphyrinogen
      oxidase (CPO), respectively. Given the dominant mode of inheritance of EPP, VP,
      AIP and HC, we first confirmed that the 200 overtly porphyric subjects (55 EPP,
      58 AIP, 56 VP; 31 HC) presented a single mutation restricted to one allele (20
      novel mutations and 162 known mutations). We then analysed the available single
      nucleotide polymorphisms (SNPs) present at high frequencies in the general
      population and spreading throughout the FECH, HMBS, PPOX and the CPO genes in
      four case-control association studies. Finally, we explored the functional
      consequences of polymorphisms on the abundance of wild-type RNA, and used
      relative allelic mRNA determinations to find out whether low-expressed HMBS, PPOX
      and the CPO alleles occur in the general population. We confirm that the wild
      type low-expressed allele phenomenon is usually operative in the mechanism of
      variable penetrance in EPP, but conclude that this is not the case in AIP and VP.
      For HC, the CPO mRNA determinations strongly suggest that normal CPO alleles with
      low-expression are present, but whether this low-expression of the wild-type
      allele could modulate the penetrance of a CPO gene defect in HC families remains
      to be ascertained.

PMID- 14669012
TI  - How synapses in the auditory system wax and wane: theoretical perspectives.
AB  - Spike-timing-dependent synaptic plasticity has recently provided an account of
      both the acuity of sound localization and the development of temporal-feature
      maps in the avian auditory system. The dynamics of the resulting learning
      equation, which describes the evolution of the synaptic weights, is governed by
      an unstable fixed point. We outline the derivation of the learning equation for
      both the Poisson neuron model and the leaky integrate-and-fire neuron with
      conductance synapses. The asymptotic solutions of the learning equation can be
      described by a spectral representation based on a biorthogonal expansion.

PMID- 14669013
TI  - Subthreshold outward currents enhance temporal integration in auditory neurons.
AB  - Many auditory neurons possess low-threshold potassium currents ( I(KLT)) that
      enhance their responsiveness to rapid and coincident inputs. We present
      recordings from gerbil medial superior olivary (MSO) neurons in vitro and
      modeling results that illustrate how I(KLT) improves the detection of brief
      signals, of weak signals in noise, and of the coincidence of signals (as needed
      for sound localization). We quantify the enhancing effect of I(KLT) on temporal
      processing with several measures: signal-to-noise ratio (SNR), reverse
      correlation or spike-triggered averaging of input currents, and interaural time
      difference (ITD) tuning curves. To characterize how I(KLT), which activates below
      spike threshold, influences a neuron's voltage rise toward threshold, i.e., how
      it filters the inputs, we focus first on the response to weak and noisy signals.
      Cells and models were stimulated with a computer-generated steady barrage of
      random inputs, mimicking weak synaptic conductance transients (the "noise"),
      together with a larger but still subthreshold postsynaptic conductance, EPSG (the
      "signal"). Reduction of I(KLT) decreased the SNR, mainly due to an increase in
      spontaneous firing (more "false positive"). The spike-triggered reverse
      correlation indicated that I(KLT) shortened the integration time for spike
      generation. I(KLT) also heightened the model's timing selectivity for coincidence
      detection of simulated binaural inputs. Further, ITD tuning is shifted in favor
      of a slope code rather than a place code by precise and rapid inhibition onto MSO
      cells (Brand et al. 2002). In several ways, low-threshold outward currents are
      seen to shape integration of weak and strong signals in auditory neurons.

PMID- 14669014
TI  - Distributed coding of sound locations in the auditory cortex.
AB  - Although the auditory cortex plays an important role in sound localization, that
      role is not well understood. In this paper, we examine the nature of spatial
      representation within the auditory cortex, focusing on three questions. First,
      are sound-source locations encoded by individual sharply tuned neurons or by
      activity distributed across larger neuronal populations? Second, do temporal
      features of neural responses carry information about sound-source location?
      Third, are any fields of the auditory cortex specialized for spatial processing?
      We present a brief review of recent work relevant to these questions along with
      the results of our investigations of spatial sensitivity in cat auditory cortex.
      Together, they strongly suggest that space is represented in a distributed
      manner, that response timing (notably first-spike latency) is a critical
      information-bearing feature of cortical responses, and that neurons in various
      cortical fields differ in both their degree of spatial sensitivity and their
      manner of spatial coding. The posterior auditory field (PAF), in particular, is
      well suited for the distributed coding of space and encodes sound-source
      locations partly by modulations of response latency. Studies of neurons recorded
      simultaneously from PAF and/or A1 reveal that spatial information can be decoded
      from the relative spike times of pairs of neurons - particularly when responses
      are compared between the two fields - thus partially compensating for the absence
      of an absolute reference to stimulus onset.

PMID- 14669015
TI  - Representation of spectrotemporal sound information in the ascending auditory
      pathway.
AB  - The representation of sound information in the central nervous system relies on
      the analysis of time-varying features in communication and other environmental
      sounds. How are auditory physiologists and theoreticians to choose an appropriate
      method for characterizing spectral and temporal acoustic feature representations
      in single neurons and neural populations? A brief survey of currently available
      scientific methods and their potential usefulness is given, with a focus on the
      strengths and weaknesses of using noise analysis techniques for approximating
      spectrotemporal response fields (STRFs). Noise analysis has been used to foster
      several conceptual advances in describing neural acoustic feature representation
      in a variety of species and auditory nuclei. STRFs have been used to
      quantitatively assess spectral and temporal transformations across mutually
      connected auditory nuclei, to identify neuronal interactions between spectral and
      temporal sound dimensions, and to compare linear vs. nonlinear response
      properties through state-dependent comparisons. We propose that noise analysis
      techniques used in combination with novel stimulus paradigms and parametric
      experiment designs will provide powerful means of exploring acoustic feature
      representations in the central nervous system.

PMID- 14669016
TI  - Gain adjustment of inhibitory synapses in the auditory system.
AB  - A group of central auditory neurons residing in the lateral superior olivary
      nucleus (LSO) responds selectively to interaural level differences and may
      contribute to sound localization. In this simple circuit, ipsilateral sound
      increases firing of LSO neurons, whereas contralateral sound inhibits the firing
      rate via activation of the medial nucleus of the trapezoid body (MNTB). During
      development, individual MNTB fibers arborize within the LSO, but they undergo a
      restriction of their boutons that ultimately leads to mature topography. A
      critical issue is whether a distinct form of inhibitory synaptic plasticity
      contributes to MNTB synapse elimination within LSO. Whole-cell recording from LSO
      neurons in brain slices from developing gerbils show robust long-term depression
      (LTD) of the MNTB-evoked IPSP/Cs when the MNTB was activated at a low frequency
      (1 Hz). These inhibitory synapses also display mixed GABA/glycinergic
      transmission during development, as assessed physiologically and
      immunohistochemically (Kotak et al. 1998). While either glycine or GABA(A)
      receptors could independently display inhibitory LTD, focal delivery of GABA, but
      not glycine, at the postsynaptic-locus induces depression. Furthermore, the
      GABA(B) receptor antagonist, SCH-50911, prevents GABA or synaptically induced
      depression. Preliminary evidence also indicated strengthening of inhibitory
      transmission (LTP) by a distinct pattern of inhibitory activity. These data
      support the idea that GABA is crucial for the expression inhibitory LTD and that
      this plasticity may underlie the early refinement of inhibitory synaptic
      connections in the LSO.

PMID- 14669017
TI  - Binaural processing in the synthesis of auditory spatial receptive fields.
AB  - The owl's auditory system computes interaural time (ITD) and interaural level
      (ILD) differences to create a two-dimensional map of auditory space. Space
      specific neurons are selective for combinations of ITD and ILD, which define,
      respectively, the horizontal and vertical dimensions of their receptive fields.
      ITD curves for postsynaptic potentials indicate that ICx neurons integrate the
      results of binaural cross correlation in different frequency bands. However, the
      difference between the main and side peaks is slight. ICx neurons further enhance
      this difference in the process of converting membrane potentials to impulse
      rates. Comparison of subthreshold postsynaptic potentials (PSPs) and spike output
      for the same neurons showed that receptive fields measured in PSPs were much
      larger than those measured in spikes in both ITD and ILD dimensions. A
      multiplication of separate postsynaptic potentials tuned to ITD and ILD can
      account for the combination sensitivity of these neurons to ITD-ILD pairs.

PMID- 14669018
TI  - The synthesis and use of the owl's auditory space map.
AB  - The barn owl ( Tyto alba) is capable of capturing prey by passive hearing alone,
      guided by a topographic map of auditory space in the external nucleus of its
      inferior colliculus. The neurons of this auditory space map have discrete spatial
      receptive fields that result from the computation of interaural differences in
      the level (ILD) and time-of-arrival (ITD) of sounds. Below we review the
      synthesis of the spatial receptive fields from the frequency-specific ITDs and
      ILDs to which the neurons are tuned, concentrating on recent studies exploiting
      virtual auditory space techniques to analyze the contribution of ILD. We then
      compared the owl's spatial discrimination, assessed behaviorally, with that of
      its space map neurons. Spatial discrimination was assessed using a novel paradigm
      involving the pupillary dilation response (PDR), and neuronal acuity was assessed
      by measuring the changes in firing rate resulting from changes in source
      location, scaled to the variance. This signal-detection-based approach revealed
      that the change in the position of the neural image on this map best explains the
      spatial discrimination measured using the PDR. We compare this result to recent
      studies in mammalian systems.

PMID- 14669019
TI  - Modeling coincidence detection in nucleus laminaris.
AB  - A biologically detailed model of the binaural avian nucleus laminaris is
      constructed, as a two-dimensional array of multicompartment, conductance-based
      neurons, along tonotopic and interaural time delay (ITD) axes. The model is based
      primarily on data from chick nucleus laminaris. Typical chick-like parameters
      perform ITD discrimination up to 2 kHz, and enhancements for barn owl perform ITD
      discrimination up to 6 kHz. The dendritic length gradient of NL is explained
      concisely. The response to binaural out-of-phase input is suppressed well below
      the response to monaural input (without any spontaneous activity on the opposite
      side), implicating active potassium channels as crucial to good ITD
      discrimination.

PMID- 14669020
TI  - Primary auditory cortex of cats: feature detection or something else?
AB  - Neurons in sensory cortices are often assumed to be "feature detectors",
      computing simple and then successively more complex features out of the incoming
      sensory stream. These features are somehow integrated into percepts. Despite many
      years of research, a convincing candidate for such a feature in primary auditory
      cortex has not been found. We argue that feature detection is actually a
      secondary issue in understanding the role of primary auditory cortex. Instead,
      the major contribution of primary auditory cortex to auditory perception is in
      processing previously derived features on a number of different timescales. We
      hypothesize that, as a result, neurons in primary auditory cortex represent
      sounds in terms of auditory objects rather than in terms of feature maps.
      According to this hypothesis, primary auditory cortex has a pivotal role in the
      auditory system in that it generates the representation of auditory objects to
      which higher auditory centers assign properties such as spatial location, source
      identity, and meaning.

PMID- 14669021
TI  - A proposed role for the Polycomb group protein dRING in meiotic sister-chromatid
      cohesion.
AB  - ORD protein is required for accurate chromosome segregation during male and
      female meiosis in Drosophila melanogaster. Null ord mutations result in random
      segregation of sister chromatids during both meiotic divisions because cohesion
      is completely abolished prior to kinetochore capture of microtubules during
      meiosis I. Previous analyses of mutant ord alleles have led us to propose that
      the C-terminal half of the ORD protein mediates protein-protein interactions that
      are essential for sister-chromatid cohesion. To identify proteins that interact
      with ORD, we conducted a yeast two-hybrid screen using an ORD bait and isolated
      dRING, a core subunit of the Drosophila Polycomb repressive complex 1. We show
      that a missense mutation in ORD completely ablates the two-hybrid interaction
      with dRING and prevents nuclear retention of the mutant ORD protein in male
      meiotic cells. Using affinity-purified antibodies generated against full-length
      recombinant dRING, we demonstrate that dRING protein is expressed in the male and
      female gonads and colocalizes extensively with ORD on the chromatin of primary
      spermatocytes during G2 of meiosis. Our results suggest a novel role for the
      Polycomb group protein dRING and are consistent with the model that interaction
      of dRING and ORD is required to promote the proper segregation of meiotic
      chromosomes.

PMID- 14669022
TI  - Cerebral anaplastic pleomorphic xanthoastrocytoma with meningeal dissemination at
      first presentation.
AB  - INTRODUCTION: Pleomorphic xanthoastrocytoma (PXA) is a rare brain glial tumour
      found in young patients. Most cases are reported as evolving low-grade neoplasms
      associated with a long survival after complete surgical resection. Some PXAs,
      however, can demonstrate secondary malignant transformation or progress with a
      short survival. Anaplastic histological features at first presentation or
      secondary meningeal dissemination have rarely been reported. CASE REPORT: We
      describe the case of a cerebral PXA in a 7-year-old girl presenting with
      anaplastic histological features and craniospinal meningeal dissemination that
      progressed rapidly with a poor outcome.

PMID- 14669023
TI  - Brainstem gliomas.
AB  - INTRODUCTION: Brainstem gliomas have historically been one of the most difficult
      pediatric cancers to treat. Tumors arising in the brainstem were once uniformly
      discounted as surgically unresectable lesions. Early neurosurgeons thought this
      location to be inoperable and fraught with disaster. The advent of computed
      tomography (CT), magnetic resonance imaging (MRI), and sophisticated
      neurophysiological monitoring techniques have significantly advanced the surgical
      treatment of these precarious lesions. REVIEW: Brainstem gliomas are now
      recognized as a heterogenous group of tumors. They have been broadly classified
      into several categories depending upon the classification scheme. All these
      classification systems provide a framework to predict growth patterns, surgical
      resectability, and overall prognosis of these tumors. These systems allow the
      surgeon to obtain a better understanding of the distinction between low-grade
      tumors and diffuse inoperable tumor types. The authors review the current
      literature and management of brainstem tumors.

PMID- 14669024
TI  - Putative phenoloxidases in the tunicate Ciona intestinalis and the origin of the
      arthropod hemocyanin superfamily.
AB  - In addition to the respiratory copper-containing proteins for which it is named,
      the arthropod hemocyanin superfamily also includes phenoloxidases and various
      copperless storage proteins (pseudo-hemocyanins, hexamerins and hexamerin
      receptors). It had long been assumed that these proteins are restricted to the
      arthropod phylum. However, in their analysis of the predicted genes in the Ciona
      intestinalis (Urochordata:Tunicata) genome, Dehal et al. (Science 298:2157-2167)
      proposed that the sea squirt lacks hemoglobin but uses hemocyanin for oxygen
      transport. While there are, nevertheless, four hemoglobin genes present in Ciona,
      we have identified and cloned two cDNA sequences from Ciona that in fact belong
      to the arthropod hemocyanin superfamily. They encode for proteins of 794 and 775
      amino acids, respectively. The amino acids required for oxygen binding and other
      structural important residues are conserved in these hemocyanin-like proteins.
      However, phylogenetic analyses and mRNA expression data suggest that the Ciona
      hemocyanin-like proteins rather act as phenoloxidases, possibly involved in
      humoral immune response. Nevertheless, the putative Ciona phenoloxidases
      demonstrate that the hemocyanin superfamily emerged before the Protostomia and
      Deuterostomia diverged and allow for the first time the unequivocal rooting of
      the arthropod hemocyanins and related proteins. Phylogenetic analyses using
      neighbor-joining and Bayesian methods show that the phenoloxidases form the most
      ancient branch of the arthropod proteins, supporting the idea that respiratory
      hemocyanins evolved from ancestors with an enzymatic function. The hemocyanins
      evolved in agreement with the expected phylogeny of the Arthropoda, with the
      Onychophora diverged first, followed by the Chelicerata and Pancrustacea. The
      position of the myriapod hemocyanins is not resolved.

PMID- 14669025
TI  - Sensitivity to spectral interaural intensity difference cues in space-specific
      neurons of the barn owl.
AB  - Barn owls use interaural intensity differences to localize sounds in the vertical
      plane. At a given elevation the magnitude of the interaural intensity difference
      cue varies with frequency, creating an interaural intensity difference spectrum
      of cues which is characteristic of that direction. To test whether space-specific
      cells are sensitive to spectral interaural intensity difference cues, pure-tone
      interaural intensity difference tuning curves were taken at multiple different
      frequencies for single neurons in the external nucleus of the inferior
      colliculus. For a given neuron, the interaural intensity differences eliciting
      the maximum response (the best interaural intensity differences) changed with the
      frequency of the stimulus by an average maximal difference of 9.4+/-6.2 dB. The
      resulting spectral patterns of these neurally preferred interaural intensity
      differences exhibited a high degree of similarity to the acoustic interaural
      intensity difference spectra characteristic of restricted regions in space.
      Compared to stimuli whose interaural intensity difference spectra matched the
      preferred spectra, stimuli with inverted spectra elicited a smaller response,
      showing that space-specific neurons are sensitive to the shape of the spectrum.
      The underlying mechanism is an inhibition for frequency-specific interaural
      intensity differences which differ from the preferred spectral pattern.
      Collectively, these data show that space-specific neurons are sensitive to
      spectral interaural intensity difference cues and support the idea that behaving
      barn owls use such cues to precisely localize sounds.

PMID- 14669026
TI  - [Classification of ocular surface disease. Part 1].
AB  - The ocular surface consists of the lid margin, conjunctiva and cornea which
      together with the tear system represent a functional entity. The diagnosis of
      ocular surface disease can be very difficult due to the similarity of various
      disease entities. The classification should be made on the pathological and
      pathophysiological characteristics of ocular surface disease. The first part of
      the classification comprises diseases of the lid margin, the tear system as well
      as diseases of the conjunctiva. Both the clinical presentation as well as the
      underlying pathophysiological and pathological characteristics of the most
      important ocular surface diseases are reviewed.

PMID- 14669027
TI  - [Dry eye disease as a complex dysregulation of the functional anatomy of the
      ocular surface. New concepts for understanding dry eye disease].
AB  - INTRODUCTION: Dry eye disease is a disorder of the tear film that results in
      epithelial damage and in a disruption of the normal homeostasis at the ocular
      surface. It is widespread and causes symptoms ranging from discomfort to
      blindness. METHODS: A review of the existing literature was used to compare
      different past and recent concepts for the understanding of dry eye disease with
      a focus on aspects of the integrating functional anatomy of the ocular surface.
      RESULTS: The understanding of the pathogenesis of dry eye disease has proceeded
      from the mere recognition of a lack of tears to a consideration of their quality
      and to the concept of wetting of the ocular surface. However, several other
      aspects as epithelial differentiation, innervation, hormonal status or immune
      protection contribute to the intact functional anatomy of the ocular surface.
      Recently it has been recognized that immunologically regulated mechanisms of
      inflammation represent a primary or secondary pathogenetic factor for dry eye
      disease. This is conceivably regulated by the cells of the physiological mucosal
      immune defence system, the eye-associated lymphoid tissue (EALT). Androgens
      represent an important trophic factor for the ocular surface and their deficiency
      predisposes to inflammation. CONCLUSION: Dry eye disease represents a complex
      dysregulation of the functional anatomy of the ocular surface that can start from
      different alterations (e.g. insufficient secretion, defects in wetting or
      innervation). Immune-based inflammation is able to interconnect and negatively
      reinforce these different pathomechanisms, resulting in a vicious circle.

PMID- 14669028
TI  - [Eye-associated lymphoid tissue (EALT) is continuously spread throughout the
      ocular surface from the lacrimal gland to the lacrimal drainage system].
AB  - INTRODUCTION: Components of the mucosal immune system (MALT) have been identified
      in the conjunctiva (as CALT) and the lacrimal drainage system (as LDALT). Their
      structural and functional relation with the established immune protection by the
      lacrimal gland is unclear. MATERIAL AND METHODS: Macroscopically normal and
      complete tissues of the conjunctiva, lacrimal drainage system and lacrimal gland
      from human body donors were investigated by analysis of translucent whole mounts,
      and using histology, immunohistology as well as scanning and transmission
      electron microscopy. RESULTS: A typical diffuse lymphoid tissue, composed of
      effector cells of the immune system (T-lymphocytes and IgA producing plasma
      cells) under an epithelium that contains the IgA transporter SC, is not isolated
      in the conjunctiva and lacrimal drainage system. It is anatomically continuous
      from the lacrimal gland along its excretory ducts into the conjunctiva and from
      there via the lacrimal canaliculi into the lacrimal drainage system. Lymphoid
      follicles occur in a majority (about 60%) and with bilateral symmetry. The
      topography of CALT corresponds to the position of the cornea in the closed eye.
      CONCLUSION: These results show that the MALT of the lacrimal gland, conjunctiva
      and lacrimal drainage system constitute an anatomical and functional unit for
      immune protection of the ocular surface. Therefore it should be integrated as an
      "eye-associated lymphoid tissue" (EALT) into the MALT system of the body. EALT
      can detect ocular surface antigens by the lymphoid follicles and can supply other
      organs and the ocular surface including the lacrimal gland with specific effector
      cells via the regulated recirculation of lymphoid cells.

PMID- 14669029
TI  - [Phantom pain after eye enucleation].
AB  - BACKGROUND: Phantom pain is a well known and extensively documented complication
      after limb amputation. Nearly all surgical disciplines have to deal with phantom
      symptoms related to different anatomical regions and organs but limited data is
      available about phantom eye pain (PEP) after enucleation. Only one pilot study is
      present in literature. It was the aim of this study to analyze a group of
      patients with a standardized surgical procedure of enucleation concerning the
      incidence of PEP and its relation to further preoperative and postoperative data.
      PATIENTS AND METHODS: A standardized questionnaire was sent to all enucleation
      patients with primary orbital implant performed between 1/1/1986 and 12/31/1995
      at Munster University. Data of 94 patients could be analyzed with regard to PEP,
      perioperative pain symptoms and further ophthalmological and surgical data.
      RESULTS: 24 of 94 patients reported PEP after enucleation. The frequency of PEP
      was less than once per month in the majority of patients (71%). 2 of 24 patients
      suffered from PEP on more than 4 days/month. Perioperative pain symptoms (ocular
      pain [OP], preoperative and postoperative headache) were reported with a higher
      proportion (each p<0.0025) in patients with PEP compared to those not affected by
      PEP. All patients with a preoperative history of OP longer than 5 years and 75%
      of patients with OP longer than 12 months of pre-enucleation OP were affected by
      PEP. CONCLUSIONS: Phantom eye pain is present in nearly 1/4 of patients after
      enucleation and is significantly related to other perioperative pain symptoms.

PMID- 14669030
TI  - [Ocular toxocariasis. Diagnostic and therapeutic options].
AB  - BACKGROUND: The diagnosis of ocular toxocariasis can be difficult and the aim of
      this study was to evaluate the benefit of ELISA testing of vitreous body fluid.
      PATIENTS AND METHODS: We present five consecutively treated patients with ocular
      symptoms of toxocariasis, three of these patients presenting with epiretinal
      membranes and subretinal granulomas were vitrectomized. Vitreous and body fluid
      and serum were tested for toxocara antibodies by ELISA. Moreover vitreous body
      fluid of 10 patients with epiretinal membranes of other origins were examined by
      the same ELISA. RESULTS: In all three operated patients toxocara antibodies were
      detected in the vitreous fluid but ELISA testing of serum samples was negative in
      two of the three patients. Visual acuity increased or remained stable in the
      operated patients. The ELISA test was negative in all vitreous fluid samples of
      the control group. CONCLUSIONS: ELISA testing of vitreous body fluid can prove
      the presence of toxocara infection when no systemic signs of infection are
      present and no antibodies are detectable in the serum. Well-timed vitrectomy is a
      suitable therapy for vitreo-retinal complications in ocular toxocariasis to
      improve prognosis and to confirm the diagnosis.

PMID- 14669031
TI  - [Immunohistochemical detection of altered low density lipoprotein (ox-LDL) in the
      vessel walls of patients with giant cell arteritis].
AB  - BACKGROUND AND PURPOSE: Recent data indicate that lipid peroxidation is
      implicated in the pathogenesis of giant cell arteritis with a close anatomic
      relationship between reactive oxygen species and oxidatively injured vascular
      tissue. PATIENTS AND METHODS: Immunohistochemistry utilizing anti-ox-LDL was
      performed on paraffin sections of isolated temporal arteries obtained from
      patients (n=23) suspected of having temporal arteritis. Enrichment as well as
      staining intensity of ox-LDL in vascular tissue was analysed by digital image
      planimetry. RESULTS: Temporal arteries with biopsy proven temporal arteritis
      (n=11) presented with significantly higher enrichment of ox-LDL in the intima
      (16.9+/-4.2% vs. 11.25+/-2.3%; p<0.01) and mean (9.6+/-2.4% vs. 6.75+/-1.8%;
      p<0.01) as compared to healthy controls. Comparable results for the staining
      intensity were found in the intimal (2.8+/-0.5 eU vs. 1.7+/-0.4 eU; p<0.01) and
      medial layer (1.55+/-0.5 eU vs. 1.04+/-0.6 eU; p<0.01) of diseased patients
      compared to controls. CONCLUSIONS: Accumulation of ox-LDL in the intimal layer,
      especially at the intima-media-border, was closely related to disruption of the
      elastica interna and adjacent vascular tissue, presumably contributing to the
      underlying process of intimal hyperplasia through unimpeded migration of smooth
      muscle and accumulation inflammatory cells.

PMID- 14669032
TI  - [Diagnosis and follow-up of non-diabetic macular edema with optical coherence
      tomography (OCT)].
AB  - INTRODUCTION: Objective and quantitative follow-up of macular edema with present
      clinical methods is limited. We studied to what extent optical coherence
      tomography (OCT) may be clinically useful in diagnosis and follow-up of non
      diabetic macular edema. PATIENTS AND METHODS: We evaluated 106 eyes with non
      diabetic macular edema retrospectively considering diagnosis, foveal retinal
      thickness in OCT, fluorescein angiographic findings and visual acuity. RESULTS:
      In 60 of 61 eyes (98%) the diagnosis of macular edema was confirmed by
      fluorescein angiography. There was only a minor correlation between visual acuity
      and foveal retinal thickness (r=0.32, p=0.001). Follow-up of 24 eyes showed a
      statistically significant decrease of foveal retinal thickness under therapy from
      420+/-165 microm to 354+/-165 microm (p=0,035) as well as a small improvement in
      visual acuity from 0.30 to 0.38 (p=0.025). CONCLUSION: OCT can diagnose macular
      edema non-invasively and thus may replace fluorescein angiography as an invasive
      method. The reduction of macular edema in the course of therapeutic measures can
      be documented objectively with OCT.

PMID- 14669033
TI  - [Severe course and contingent risk factors in optic neuropathy and myelopathy
      after tuberculostatics].
AB  - A male patient with tuberculous lymphadenopathy was treated with a four-fold
      therapy of ethambutol, isoniacide, rifampicin and pyracinamide. After 10 weeks
      the patient suffered from photophobia. Although ethambutol was discontinued
      vision decreased and visual field defects occurred as well as signs of
      myelopathy. Isoniacide was then discontinued and in the subsequent phase the
      vision was slowly restored over a period of 36 months. The combined toxicity of
      ethambutol and isoniacide seems to have been the main cause of the severe and
      protracted optic neuropathy.

PMID- 14669034
TI  - [Examination of preschool children for refractive errors. First experience using
      a handheld autorefractor].
AB  - BACKGROUND: Since ametropia is a leading cause of amblyopia refractive screening
      of preschool children is recommended. Measurement of refraction using tabletop
      autorefractors can be difficult or impossible due to lack of cooperation in this
      age group. The intention of the present study is to evaluate the use of a new
      handheld autorefractor for screening in kindergartens. METHODS: A total of 216
      children aged 3.5-4.5 years were examined without cycloplegia using the handheld
      autorefractor (SureSight, Welch Allyn) in their kindergartens. RESULTS: Using the
      test device the majority of the examined eyes showed mild hyperopia (on average
      +1.18+/-0.87 dpt spherical equivalent) and mild astigmatism (on average 0.60+/
      0.46 dpt cylinder power). The reproducibility of repeated autorefractor readings
      was higher for cylinder power and axis than for the spherical equivalent.
      Autorefractor readings of 55 eyes could be compared with the results of
      cycloplegic retinoscopy. The results were similar between the two measurements
      with differences of no more than 0.5 dpt in 18.2% for the spherical equivalent,
      in 82.1% for cylinder power, and in 66.6% for axis (weighted axis difference).
      There was adequate cooperation in 99.5% of the children. CONCLUSION: The handheld
      autorefractor proved an accuracy of measurement comparable to that of
      conventional tabletop autorefractors for cylinder power and axis with limitations
      in accuracy for the spherical equivalent. Validity and threshold values for
      relevant abnormalities are to be evaluated in further studies. By the high
      cooperation rate the instrument proved useful for screening examinations in
      preschool children.

PMID- 14669035
TI  - [Schnyder's crystalline corneal dystrophy. Further narrowing of the linkage
      interval at chromosome 1p34.1-p36?].
AB  - BACKGROUND: Schnyder's crystalline corneal dystrophy (SCCD) is a rare autosomal
      dominant disease and can occur in association with hyperlipoproteinemia. The
      disease has been mapped to chromosome 1p34.1-p36. CASE REPORT: We report on a 66
      year-old woman and her son with Schnyder's crystalline corneal dystrophy. The
      mother had type IV hyperlipoproteinemia and hypercholesterolemia while her son
      had hypercholesterolemia with elevated LDL-cholesterol. Analysis of
      microsatellite markers within the candidate interval of 1p34.1-p36 showed that
      the affected son and his unaffected brother had inherited different alleles only
      for the proximal marker D1S228 from their affected mother. CONCLUSIONS: The
      haplotype analysis suggests that either recombination has occurred, which would
      allow the candidate interval to be narrowed down, or alternatively, the SCCD in
      the reported family is not linked to chromosome 1, which would be a first
      indication of genetic heterogeneity in this disease. To reduce the risk of
      cardiovascular disease, hyperlipidemia should always be excluded in patients with
      Schnyder's crystalline corneal dystrophy.

PMID- 14669036
TI  - [Unilateral visual deterioration due to macular tumour of unclear origin. 32-year
      old female patient with sudden low vision in the right eye].

PMID- 14669037
TI  - [Unclear, bilateral retinal dystrophy. 35-year old female patient with glare
      sensation].

PMID- 14669038
TI  - Magnetic resonance imaging in the evaluation of treatment response of lateral
      epicondylitis of the elbow.
AB  - The purpose of this study was to investigate the treatment response in lateral
      epicondylitis (tennis elbow) by MRI. Magnetic resonance imaging was obtained in
      30 patients with clinical symptoms of lateral epicondylitis of the elbow using T1
      , T2- and T2-weighted fat-saturated (FS) sequences. The patients were randomised
      to either i.m. corticosteroid injection ( n=16) or immobilisation in a wrist
      splint ( n=14). Magnetic resonance imaging of the elbow was performed on a 1.5-T
      MR system at baseline and after 6 weeks. The extensor carpi radialis (ECRB)
      tendon, the radial collateral ligament, lateral humerus epicondyle at tendon
      insertion site, joint fluid and signal intensity changes within brachio-radialis
      and anconeus muscles were evaluated on the MR unit's workstation before and after
      6 weeks of treatment. The MRI was performed once in 22 healthy controls for
      comparison and all images evaluated by an investigator blinded to the clinical
      status of the subjects. The MR images showed thickening with separation of the
      ECRB tendon from the radial collateral ligament and abnormal signal change in 25
      of the 30 patients on the T1-weighted sequences at inclusion. The signal
      intensity of the ECRB tendon was increased in 24 of the 30 patients with lateral
      epicondylitis of the elbow on the T2-weighted FS sequences. In the patients there
      were no associations between pathologically signal intensity within the ECRB
      tendon on T1- and T2-weighted sequences and the degree of self-reported pain
      (Dumbells test) at inclusion. In general, the MRI changes persisted in the
      patients at follow-up after 6 weeks despite clinical remission. The increased
      signal intensity within the extensor tendon is indicative of lateral
      epicondylitis humeri. The changes in signal intensity and morphology of ECRB
      tendon seem to be chronic and may persist despite clinical improvement.

PMID- 14669039
TI  - Comparison of four modulators of drug metabolism as protectants against the
      hepatotoxicity of the novel antitumor drug yondelis (ET-743) in the female rat
      and in hepatocytes in vitro.
AB  - PURPOSE: Yondelis (ET-743), a tetrahydroisoquinoline alkaloid isolated from a
      marine tunicate, is a novel drug with demonstrated anticancer activity in early
      clinical trials against sarcoma, breast and ovarian carcinoma. Yondelis has
      myelotoxic and hepatotoxic side effects, the latter reflected by reversible
      transaminitis and cholangitis. In the female rat pretreatment with high-dose
      dexamethasone has been shown to abrogate yondelis-mediated hepatotoxicity, an
      effect tentatively linked to its ability to induce cytochrome P450 CYP3A
      isoenzymes, which metabolize yondelis. Here we tested the hypothesis that
      pretreatment of rats with modulators of hepatic drug metabolism, beta
      naphthoflavone, phenobarbitone or N-acetylcysteine, protect rat livers against
      the effects of yondelis. METHODS: Female rats received yondelis (40 microg/kg
      intravenously) and liver damage in vivo was assessed in terms of changes in
      plasma levels of bilirubin, alkaline phosphatase (ALP) and aspartate
      aminotransferase (AST) and by histopathology. In order to investigate yondelis
      toxicity in vitro, hepatocytes isolated from untreated rats or from rats
      pretreated with dexamethasone, beta-naphthoflavone or phenobarbitone were
      maintained in culture and exposed to yondelis. RESULTS: Pretreatment with beta
      naphthoflavone and phenobarbitone ameliorated yondelis-mediated hepatotoxicity in
      vivo. The former abrogated plasma indicators on day 3, but hardly on day 6, and
      the latter suppressed elevation of bilirubin, but not of ALP or AST. Pretreatment
      with N-acetylcysteine did not protect from, but slightly exacerbated, yondelis
      induced liver changes. Hepatocytes from naive animals or from pretreated rats did
      not differ in their susceptibility towards yondelis-induced cytotoxicity in
      vitro. Nor did inclusion of N-acetylcysteine (1 m M) in the cellular incubation
      medium affect yondelis-induced hepatocytotoxicity. CONCLUSIONS: The results
      suggest that certain inducers of cytochrome P450 enzymes such as dexamethasone
      and beta-naphthoflavone can protect rat liver against the unwanted effects of
      yondelis, but such protection cannot be mimicked in in vitro experiments using
      liver cells in culture.

PMID- 14669040
TI  - Mantle cell lymphoma: established therapeutic options and future directions.
AB  - During the last few years, new insights into the biology of mantle cell lymphoma
      have been obtained. However, with a median survival of only 3 years, mantle cell
      lymphoma remains the lymphoma subtype with the poorest prognosis. At initial
      diagnosis most patients present with advanced Ann Arbor stage III or IV and
      conventional chemotherapy hardly alters the continuously declining survival
      curve. Recently, two prospective randomized studies of the German Low Grade
      Lymphoma Study Group (GLSG) clearly confirmed the superiority of a combined
      immunochemotherapy. In a randomized study of the European mantle cell lymphoma
      Network, consolidation with myeloablative radiochemotherapy followed by
      autologous stem cell transplantation improved the progression-free survival in
      patients younger than 65 years. However, relapses are still observed at a high
      frequency. Thus, new therapeutic strategies such as radioactively labeled
      antibodies or molecular targeting agents (e.g. Bortezomib or flavopiridol) are
      urgently warranted to further improve the clinical outcome of mantle cell
      lymphoma.

PMID- 14669056
TI  - Biotechnology and molecular biology of the alpha-glucosidase inhibitor acarbose.
AB  - The alpha-glucosidase inhibitor acarbose, O-[4,6-dideoxy-4[1 s-(1,4,6/5)-4,5,6
      trihydroxy-3-hydroxymethyl-2-cyclohexen-1-yl]-amino-alpha-D-glucopyranosyl]-(1-
      >4)- O-alpha-D-glucopyranosyl-(1-->4)-D-glucopyranose, is produced in large-scale
      fermentation by the use of strains derived from Actinoplanes sp. SE50. It has
      been used since 1990 in many countries in the therapy of diabetes type II, in
      order to enable patients to better control blood sugar contents while living with
      starch-containing diets. Thus, it is one of the latest successful products of
      bacterial secondary metabolism to be introduced into the pharmaceutical world
      market. Cultures of Actinoplanes sp. also produce various other acarbose-like
      components, of which component C is hard to separate during downstream
      processing, which is one of the most modern work-up processes developed to date.
      The physiology, genetics and enzymology of acarbose biosynthesis and metabolism
      in the producer have been studied to some extent, leading to the proposal of a
      new pathway and metabolic cycle, the "carbophore". These data could give clues
      for further biotechnological developments, such as the suppression of side
      products, enzymological or biocombinatorial production of new metabolites and the
      engineering of production rates via genetic regulation in future.

PMID- 14669057
TI  - An easy method for screening and isolating rod mutants of Bacillus subtilis.
AB  - A convenient and rapid method for screening and identifying rod mutants of
      Bacillus subtilis is described. At the restrictive temperature (45 degrees C),
      all rod mutants of B. subtilis screened lost their ability to sporulate. The
      morphology and colour of mutant colonies grown on sporulation agar plates
      differed from those of rod+ cells, which were able to sporulate even at elevated
      temperature. These characteristics provide an alternative approach for the
      identification of rod mutants in B. subtilis culture by streaking the cells onto
      a minimal glucose agar plate and incubating at the restrictive temperature. After
      30 h of incubation at this temperature, rod mutants are easily identified. This
      method will facilitate the screening and isolation of rod mutants of B. subtilis.

PMID- 14669058
TI  - 3-hydroxypropionaldehyde: applications and perspectives of biotechnological
      production.
AB  - 3-hydroxypropionaldehyde (3-HPA) forms, together with HPA-hydrate and HPA-dimer,
      a dynamic, multi-component system (HPA system) used in food preservation, as a
      precursor for many modern chemicals such as acrolein, acrylic acid, and 1,3
      propanediol (1,3-PDO), and for polymer production. 3-HPA can be obtained both
      through traditional chemistry and bacterial fermentation. To date, 3-HPA has been
      produced from petrochemical resources as an intermediate in 1,3-PDO production.
      In vivo, glycerol is converted in one enzymatic step into 3-HPA. The 3-HPA
      producing Lactobacillus reuteri is used as a probiotic in the health care of
      humans and animals. The biotechnological production of 3-HPA from renewable
      resources is desirable both for use of 3-HPA in foods and for the production of
      bulk chemicals. The main challenge will be the efficient production and recovery
      of pure 3-HPA.

PMID- 14669059
TI  - Molecular cloning and characterization of calreticulin from rainbow trout (
      Oncorhynchus mykiss).
AB  - Calreticulin (CRT) is a highly conserved, high-capacity, calcium-binding protein
      shared among vertebrates, invertebrates and higher plants. Its biological
      importance, highlighted by its highly conserved nature, is supported by its
      crucial physiological and immunological functions. Within the endoplasmic
      reticulum, CRT serves as a calcium modulator and a lectin-like chaperone for
      glycoproteins, especially class I major histocompatibility receptors. To date,
      CRT cDNA clones have been isolated from a wide range of phyla, yet little is
      known about this gene in fish species, the largest and most diverse group of
      jawed vertebrates. This report describes the cloning of a cDNA from a rainbow
      trout pronephros library that encodes a deduced 419-amino acid protein, which
      includes a predicted 20-amino acid signal peptide and has a 69% amino acid
      identity to both murine and human CRT. Like its mammalian counterparts, this cDNA
      contains conserved cysteine residues believed to form a disulphide bond, a
      proline-rich region which includes a potential N-glycosylation site, and a highly
      acidic C-terminal domain terminating with the endoplasmic reticulum retrieval
      sequence, KDEL. Reverse transcription tissue-distribution assays indicate it is
      ubiquitously expressed in all tissues tested with highest expression in liver,
      while Southern blotting indicates it is a single copy gene.

PMID- 14669061
TI  - Radiological approach to disorders of arterial brain vessels associated with
      childhood arterial stroke-a comparison between MRA and contrast angiography.
AB  - Recent studies of arterial ischaemic stroke in children have emphasised the
      higher frequency of cerebral arterial abnormalities than believed previously,
      explaining some of the strokes thought to have been idiopathic. Moreover,
      recurrent strokes are significantly more frequent in children with multiple risk
      factors, including those with demonstrable vascular abnormalities. Thus, cerebral
      arterial imaging is essential for the understanding and therapeutic approach to
      this pathology. Contrast angiography (CA) is the reference examination for the
      diagnosis of cerebral arterial abnormalities, but MR angiography (MRA) is a
      sensitive and non-invasive method to evaluate the vasculopathy of childhood
      stroke. In this article we highlight recent data concerning localisation and
      characterisation of arterial lesions and discuss the yield of MRA compared with
      CA.

PMID- 14669060
TI  - Arranging the elements of the potassium channel: the T1 domain occludes the
      cytoplasmic face of the channel.
AB  - The voltage-gated potassium channel is currently one of the few membrane proteins
      where functional roles have been mapped onto specific segments of sequence.
      Although high-resolution structures of the transmembrane portions of three
      bacterial potassium channels, the tetramerization domain and the cytoplasmic
      "ball" are available, their relative spatial arrangement in mammalian channels
      remains a matter of ongoing debate. Cryo-electron microscopic images of the six
      transmembrane voltage-gated Kv channel have been reconstructed at up to 18 A
      resolution, revealing that the T1 domain tetramerizes and is suspended below the
      transmembrane segments. However, the resolution of these images is insufficient
      to reveal the location of the third piece of the puzzle, the inactivating ball
      domain. We have used the aberrant interactions observed in a series of chimaeric
      channels to establish that an assembled T1 domain restricts access to the
      cytoplasmic face of the channel, suggesting that the N-terminal "ball and chain"
      may be confined in the space between the T1 domain and the transmembrane portion
      of the channel.

PMID- 14669062
TI  - Computer-assisted detection of pulmonary nodules: preliminary observations using
      a prototype system with multidetector-row CT data sets.
AB  - The continued revolution in multidetector-row CT (MDCT) scanning increases the
      quality of lung imaging but at the cost of a greater burden of data for review
      and interpretation. This article discusses our preliminary experience with
      prototype software for lung nodule detection and characterization using MDCT data
      sets. We discuss the potential role of computer-assisted detection (CAD) as
      applied to the automatic detection of lung nodules. We also review the process of
      CAD, outline its potential results, and explore how it may fit into existing
      radiology practice. Finally, we discuss MDCT data-acquisition parameters and how
      they may affect the performance of CAD.

PMID- 14669063
TI  - Determining the view of chest radiographs.
AB  - Automatic identification of frontal (posteroanterior/anteroposterior) vs. lateral
      chest radiographs is an important preprocessing step in computer-assisted
      diagnosis, content-based image retrieval, as well as picture archiving and
      communication systems. Here, a new approach is presented. After the radiographs
      are reduced substantially in size, several distance measures are applied for
      nearest-neighbor classification. Leaving-one-out experiments were performed based
      on 1,867 radiographs from clinical routine. For comparison to existing
      approaches, subsets of 430 and 5 training images are also considered. The overall
      best correctness of 99.7% is obtained for feature images of 32 x 32 pixels, the
      tangent distance, and a 5-nearest-neighbor classification scheme. Applying the
      normalized cross correlation function, correctness yields still 99.6% and 99.3%
      for feature images of 32 x 32 and 8 x 8 pixel, respectively. Remaining errors are
      caused by image altering pathologies, metal artifacts, or other interferences
      with routine conditions. The proposed algorithm outperforms existing but
      sophisticated approaches and is easily implemented at the same time.

PMID- 14669064
TI  - Soft copy display requirements for digital mammography.
AB  - One of the advantages of digital mammography is to display mammograms on softcopy
      (electronic displays). Softcopy display of mammography is challenging because of
      the spatial and contrast resolution demands present in mammograms. We have
      designed and developed a softcopy mammography display application, Mammoview,
      which is capable of allowing radiologists to read mammograms as quickly and as
      accurately as they can on film alternators. We review the studies using Mammoview
      to elucidate the requirements of a successful softcopy display station. The
      design and development of the Mammoview softcopy display station are described in
      this article, and results of several studies using Mammoview are reported,
      including subjective feedback from Radiological Society of North America (RSNA)
      conference demonstrations, and clinical studies measuring performance in terms of
      speed and accuracy. Additional analysis of user interactions and user feedback is
      used to study the successes and shortcomings of mammography display stations like
      Mammoview. Overall, radiologist readings using Mammoview have been shown to be as
      fast and as accurate as readings using mammography film alternators. However,
      certain parts of the softcopy interface were more successful than their film
      counterparts, whereas others were less successful. Data analysis of the recorded
      human-computer interactions for the softcopy component of the clinical trial
      indicate statistically significant correlations between the difference in review
      time of softcopy versus alternator readings and three factors: the number of
      interactions, the reader, and the size of the image being reviewed. The first
      factor (number of interactions) suggests that simpler interfaces require less
      time to use; the second factor, the reader, supports previous findings that
      radiologists vary in how fast they read screening mammography studies; the third,
      size of image, suggests that the speed of softcopy review is increased relative
      to film readings when images are significantly larger than the display size.
      Feedback from radiologists using the system in clinical trials and at
      demonstration exhibits at RSNA indicated good acceptance of the interface and
      easy adaptation. Radiologists indicated that they felt comfortable using the
      interface, and that they would use such a softcopy interface in clinical
      practice. Finally, preliminary work suggests that the addition of a simple
      interaction to incorporate computer-aided detection (CAD) results would improve
      reading accuracy without significantly increasing reader times.

PMID- 14669065
TI  - Assessment of a novel, high-resolution, color, AMLCD for diagnostic medical image
      display: luminance performance and DICOM calibration.
AB  - This article documents the results of the first in a series of experiments
      designed to evaluate the suitability of a novel, high resolution, color, digital,
      liquid crystal display (LCD) panel for diagnostic quality, gray scale image
      display. The goal of this experiment was to measure the performance of the
      display, especially with respect to luminance. The panel evaluated was the IBM
      T221 22.2" backlit active matrix liquid crystal display (AMLCD) with native
      resolution of 3840 x 2400 pixels. Taking advantage of the color capabilities of
      the workstation, we were able to create a 256-entry grayscale calibration look-up
      table derived from a palette of 1786 nearly gray luminance values. We also
      constructed a 256-entry grayscale calibration look-up table derived from a
      palette of 256 true gray values for which the red, green, and blue values were
      equal. These calibrations will now be used in our evaluation of human contrast
      detail perception on this LCD panel.

PMID- 14669066
TI  - Tools for managing image flow in the modality to clinical-image-review chain.
AB  - Web-based clinical-image viewing is commonplace in large medical centers. As
      demands for product and performance escalate, physicians, sold on the concept of
      "any image, anytime, anywhere," fret when image studies cannot be viewed in a
      time frame to which they are accustomed. Image delivery pathways in large medical
      centers are oftentimes complicated by multiple networks, multiple picture
      archiving and communication systems (PACS), and multiple groups responsible for
      image acquisition and delivery to multiple destinations. When studies are
      delayed, it may be difficult to rapidly pinpoint bottlenecks. Described here are
      the tools used to monitor likely failure points in our modality to clinical-image
      viewing chain and tools for reporting volume and throughput trends. Though
      perhaps unique to our environment, we believe that tools of this type are
      essential for understanding and monitoring image-study flow, re-configuring
      resources to achieve better throughput, and planning for anticipated growth.
      Without such tools, quality clinical-image delivery may not be what it should.

PMID- 14669067
TI  - Impact of electronic signature on radiology report turnaround time.
AB  - The purpose of this study was to measure the impact of electronic signature on
      report turnaround time. The Radiology Information System (RIS) database was
      interrogated to obtain a file containing all examinations recorded within a one
      month period. Two sectors were specifically studied: abdominal ultrasound and
      chest radiography. Each of these sectors had one reader per day. The periods
      studied were October 2001 (before implementation of electronic signature) and
      February 2002 (3 months after electronic signature implementation). For the
      abdominal ultrasound examinations, the median time from transcription to final
      signature decreased from 11 days to 3 days with the introduction of electronic
      signature ( P < 0.001). For the chest radiographs, the median time from
      transcription to final signature decreased from 10 days to 5 days with the
      introduction of electronic signature ( P < 0.001). Electronic signature
      significantly shortens the time interval between transcription and finalization
      of radiology reports.

PMID- 14669068
TI  - From traditional reading rooms to a soft copy environment: radiologist
      satisfaction survey.
AB  - Academic radiologists are experiencing increased clinical workloads. New
      technology such as picture archiving and communication systems (PACS) are often
      justified on the premise of increased efficiency. The authors believe that
      efficiency can be influenced by the image interpretation environment, and thus
      they set out to establish baseline satisfaction levels with this environment. The
      authors surveyed 90 Indiana University (IU) faculty radiologists, fellows, and
      residents. Their survey was implemented with a questionnaire sent via e-mail.
      Questions focused on satisfaction with the current soft-copy reading environments
      and preferences regarding improvements. Of the 90 radiologists surveyed, 55 (61%)
      responded. Several key findings emerged: (1) Overall satisfaction with the soft
      copy environment is low, with nearly half (46%) of respondents rating themselves
      as "very dissatisfied" or "dissatisfied." (2) Faculty are least satisfied
      regarding work space ergonomics, room layout, and amount of work space.
      Appropriate lighting also emerged as an area with low satisfaction and high
      importance. (3) Ninety-eight percent of respondents indicated that an "ideal"
      soft-copy environment would have a positive effect on their efficiency. The
      dissatisfaction with the current soft-copy interpretation environments used by
      the IU radiologists indicates that this is an area that requires attention.
      Furthermore, there may be a direct relationship between radiologist efficiency
      and satisfaction with the image interpretation environment. Attention should be
      focused on this environment during a soft-copy technology implementation to
      ensure that planned efficiency gains are realized.

PMID- 14669069
TI  - Acrylonitrile potentiates noise-induced hearing loss in rat.
AB  - Acrylonitrile, one of the 50 most commonly produced industrial chemicals, has
      recently been identified as a promoter of noise-induced hearing loss (NIHL). This
      agent has the potential to produce oxidative stress through multiple pathways. We
      hypothesize that acrylonitrile potentiates NIHL as a consequence of oxidative
      stress. The objectives of this study were to characterize acrylonitrile exposure
      conditions that promote permanent NIHL in rats and determine the ability of this
      nitrile to produce auditory dysfunction by itself. Additionally, we sought to
      determine whether a spin-trap agent that can form adducts with ROS would protect
      against the effects of acrylonitrile. Acrylonitrile administration produced
      significant elevation in NIHL detected as a loss in compound action potential
      sensitivity. The effect was particularly robust for high-frequency tones and
      particularly when acrylonitrile and noise were given on repeated occasions.
      Acrylonitrile by itself did not disrupt threshold sensitivity. Administration of
      the spin-trap agent phenyl- N- tert-butylnitrone (PBN), given to rats prior to
      acrylonitrile and noise, did block the elevation of NIHL by acrylonitrile.
      However, PBN at the dose and time interval given was ineffective in protecting
      auditory function in subjects exposed to noise alone. The results suggest that
      oxidative stress may play a role in the promotion of NIHL by acrylonitrile.

PMID- 14669070
TI  - Usefulness of immunoblotting and Goldmann-Witmer coefficient for biological
      diagnosis of toxoplasmic retinochoroiditis.
AB  - Toxoplasmosis is a frequent cause of retinochoroiditis. Although the diagnosis
      relies mainly on ophthalmological examination, biological approaches are
      particularly useful in patients with atypical lesions. In a prospective study to
      determine the value of immunoblotting and immune load calculation in the
      diagnosis of active toxoplasmic retinochoroiditis, aqueous humor samples from 21
      patients with retinochoroiditis and 5 control patients with cataracts were
      tested. Immune load was calculated on the basis of intraocular antibody
      production. The immune load ratio between aqueous humor and serum (Goldmann
      Witmer coefficient) was significant (i.e. >2) in 9 of the 17 (53%) patients with
      retrospectively documented toxoplasmic retinochoroiditis. Immunoblotting
      suggested local antibody production in 10 of 17 (59%) patients. The combination
      of the two techniques gave a sensitivity of 71% (12/17). Both techniques were
      negative in the four patients in whom the final diagnosis of toxoplasmic
      retinochoroiditis was negative and in the five patients with cataracts. These
      results confirm the value of combining these two techniques. Moreover,
      immunoblotting has the advantages of being easy to perform and of requiring a
      very small sample.

PMID- 14669071
TI  - A case of multiorgan failure following interruption of antiretroviral treatment.
AB  - Reported here is an exceptional case of acute retroviral syndrome resembling
      septic shock that occurred in a chronic HIV-infected patient shortly following
      planned interruption of antiretroviral treatment. The therapeutic strategy, which
      is aimed at improving the immunological control of HIV infection, can therefore
      be deleterious in chronically infected patients and should be avoided outside of
      closely monitored clinical trials.

PMID- 14669072
TI  - Haemophilus parainfluenzae: an underdiagnosed pathogen of biliary tract
      infections?
AB  - Presented here is a case of monobacterial peritonitis complicating cholecystitis
      and caused by an uncommon agent of gastrointestinal infections, Haemophilus
      parainfluenzae. The pathogenic role of this organism in digestive infections,
      particularly in those of the biliary tract, has been reported increasingly though
      sporadically. Indeed, it has been shown to be a coloniser of the gastrointestinal
      tract, and a recent hypothesis of an ascending route of infection to the biliary
      tract has been postulated to partly explain its pathogenicity. More frequent
      identification of Haemophilus parainfluenzae as a causal agent of biliary tract
      infection would probably be obtained through the use of specific culture media,
      since its potential implication has been demonstrated.

PMID- 14669073
TI  - Efficacy and safety of cefotaxime in combination with metronidazole for empirical
      treatment of brain abscess in clinical practice: a retrospective study of 66
      consecutive cases.
AB  - Sixty-six consecutive patients with brain abscesses referred to a department of
      neurosurgery during a 10-year period and treated with cefotaxime were studied
      retrospectively by means of a prospectively designed protocol whose main areas of
      emphasis were duration of antibiotic treatment, sterilization rate, clinical
      outcome in relation to prognostic factors, and side effects. Sixty-two of these
      patients were treated additionally with metronidazole, and surgery was performed
      in 53 patients. Mental status was altered in 33 patients, 11 of whom were
      comatose. Rupture of the abscess into the ventricles occurred in eight patients.
      Death was attributable to brain abscess formation in three patients (4.5%). Forty
      six percent of the surviving patients recovered without any neurological
      deficits. Reversible adverse reactions, which occurred in 38 patients, were the
      most common reason for withdrawal of cefotaxime. In 76% of these cases, there was
      a significant improvement before the onset of the adverse reaction. The median
      duration of parenteral antibiotic treatment was 36, 41, 22, and 46 days in
      patients treated with excision, aspiration, evacuation of subdural empyema, and
      antibiotics alone, respectively. Taking prognostic factors into consideration,
      mortality attributable to brain abscess was lower than previously reported. This
      finding, along with the abscess sterilization results, indicates that cefotaxime
      in combination with metronidazole is a highly effective treatment but is
      associated with a high frequency of reversible side effects. The results indicate
      that a shorter duration of treatment should be investigated.

PMID- 14669074
TI  - Short-term memory effects on the representation of two-dimensional space in the
      rhesus monkey.
AB  - Human subjects represent the location of a point in 2D space using two
      independent dimensions (x-y in Euclidean or radius-angle in polar space), and
      encode location in memory along these dimensions using two levels of
      representation: a fine-grain value and a category. Here we determined whether
      monkeys possessed the ability to represent location with these two levels of
      coding. A rhesus monkey was trained to reproduce the location of a dot in a
      circle by pointing, after a delay period, on the location where a dot was
      presented. Five different delay periods (0.5-5 s) were used. The results showed
      that the monkey used a polar coordinate system to represent the fine-grain
      spatial coding, where the radius and angle of the dots were encoded
      independently. The variability of the spatial response and reaction time
      increased with longer delays. Furthermore, the animal was able to form a
      categorical representation of space that was delay-dependent. The responses
      avoided the circumference and the center of the circle, defining a categorical
      radial prototype around one third of the total radial length. This radial
      category was observed only at delay durations of 3-5 s. Finally, the monkey also
      formed angular categories with prototypes at the obliques of the quadrants of the
      circle, avoiding the horizontal and vertical axes. However, these prototypes were
      only observed at the 5-s delay and on dots lying on the circumference. These
      results indicate that monkeys may possess spatial cognitive abilities similar to
      humans.

PMID- 14669075
TI  - Are readers of our face readers of our minds? Dogs (Canis familiaris) show
      situation-dependent recognition of human's attention.
AB  - The ability of animals to use behavioral/facial cues in detection of human
      attention has been widely investigated. In this test series we studied the
      ability of dogs to recognize human attention in different experimental situations
      (ball-fetching game, fetching objects on command, begging from humans). The
      attentional state of the humans was varied along two variables: (1) facing versus
      not facing the dog; (2) visible versus non-visible eyes. In the first set of
      experiments (fetching) the owners were told to take up different body positions
      (facing or not facing the dog) and to either cover or not cover their eyes with a
      blindfold. In the second set of experiments (begging) dogs had to choose between
      two eating humans based on either the visibility of the eyes or direction of the
      face. Our results show that the efficiency of dogs to discriminate between
      "attentive" and "inattentive" humans depended on the context of the test, but
      they could rely on the orientation of the body, the orientation of the head and
      the visibility of the eyes. With the exception of the fetching-game situation,
      they brought the object to the front of the human (even if he/she turned his/her
      back towards the dog), and preferentially begged from the facing (or seeing)
      human. There were also indications that dogs were sensitive to the visibility of
      the eyes because they showed increased hesitative behavior when approaching a
      blindfolded owner, and they also preferred to beg from the person with visible
      eyes. We conclude that dogs are able to rely on the same set of human facial cues
      for detection of attention, which form the behavioral basis of understanding
      attention in humans. Showing the ability of recognizing human attention across
      different situations dogs proved to be more flexible than chimpanzees
      investigated in similar circumstances.

PMID- 14669076
TI  - Incorporation of either molybdenum or tungsten into formate dehydrogenase from
      Desulfovibrio alaskensis NCIMB 13491; EPR assignment of the proximal iron-sulfur
      cluster to the pterin cofactor in formate dehydrogenases from sulfate-reducing
      bacteria.
AB  - We report the characterization of the molecular properties and EPR studies of a
      new formate dehydrogenase (FDH) from the sulfate-reducing organism Desulfovibrio
      alaskensis NCIMB 13491. FDHs are enzymes that catalyze the two-electron oxidation
      of formate to carbon dioxide in several aerobic and anaerobic organisms. D.
      alaskensis FDH is a heterodimeric protein with a molecular weight of 126+/-2 kDa
      composed of two subunits, alpha=93+/-3 kDa and beta=32+/-2 kDa, which contains
      6+/-1 Fe/molecule, 0.4+/-0.1 Mo/molecule, 0.3+/-0.1 W/molecule, and 1.3+/-0.1
      guanine monophosphate nucleotides. The UV-vis absorption spectrum of D.
      alaskensis FDH is typical of an iron-sulfur protein with a broad band around 400
      nm. Variable-temperature EPR studies performed on reduced samples of D.
      alaskensis FDH showed the presence of signals associated with the different
      paramagnetic centers of D. alaskensis FDH. Three rhombic signals having g-values
      and relaxation behavior characteristic of [4Fe-4S] clusters were observed in the
      5-40 K temperature range. Two EPR signals with all the g-values less than two,
      which accounted for less than 0.1 spin/protein, typical of mononuclear Mo(V) and
      W(V), respectively, were observed. The signal associated with the W(V) ion has a
      larger deviation from the free electron g-value, as expected for tungsten in a
      d(1) configuration, albeit with an unusual relaxation behavior. The EPR
      parameters of the Mo(V) signal are within the range of values typically found for
      the slow-type signal observed in several Mo-containing proteins belonging to the
      xanthine oxidase family of enzymes. Mo(V) resonances are split at temperatures
      below 50 K by magnetic coupling with one of the Fe/S clusters. The analysis of
      the inter-center magnetic interaction allowed us to assign the EPR
      distinguishable iron-sulfur clusters with those seen in the crystal structure of
      a homologous enzyme.

PMID- 14669077
TI  - Serum levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) in colorectal
      cancer patients.
AB  - PURPOSE: Expression of tissue inhibitor of metalloproteinases (TIMP)-1 in
      colorectal cancer tissue is known to be related to disease progression; however,
      the clinical significance of measuring the blood level of TIMP-1, which we
      evaluate herein, has not yet been clarified. METHODS: The serum level of TIMP-1
      was measured by a one-step enzyme immunoassay in 123 patients who underwent
      resection of primary colorectal cancer. RESULTS: An elevated level of serum TIMP
      1 was associated with advanced Dukes' stage ( P = 0.03), greater diameter of the
      primary tumor ( P = 0.03), more lymph node metastasis ( P = 0.04), and liver
      metastasis ( P < 0.001). There was a weakly positive correlation between the
      serum carcinoembryonic antigen (CEA) level and the serum TIMP-1 level. In
      patients who underwent potentially curative resection, the disease-free survival
      was not different between those with a high TIMP-1 level (>=203.5 ng/ml, n = 32)
      and those with a low TIMP-1 level (<203.5 ng/ml, n = 66, P = 0.62). In patients
      with Dukes' stage D cancer who underwent noncurative resection, the survival
      times were not different between those with a high TIMP-1 level ( n = 13) and
      those with a low TIMP-1 level ( n = 10, P = 0.20). CONCLUSIONS: Elevated levels
      of serum TIMP-1 reflect the extent of colorectal cancer, without a close
      correlation with the serum CEA level. These findings suggest that measuring the
      serum TIMP-1 level would not help to predict the prognosis of patients with
      colorectal cancer.

PMID- 14669078
TI  - Intestinal rotation anomalies in childhood: review of 22 years' experience.
AB  - PURPOSE: We review our experience of treating intestinal rotation anomalies in
      infants and children in the 22-year period between 1978 and 2000. METHODS: The
      type of operation performed, postoperative complications, and mortality were
      compared in three age groups. Group 1 consisted of neonates <1 month old, Group 2
      consisted of infants aged <1 year old, and Group 3 consisted of children aged >1
      year old. RESULTS: There were 101 infants and children, with a female : male
      ratio of 2 : 1. Of the 101 patients, 72 (71%) were neonates, with a mean age of
      11.8 days (range 1-28 days); 20 (19.8%) were under the age of 1 year, with a mean
      age of 6.7 months (range 1-12 months); and 9 (8.9%) were >1 year of age, with a
      mean age of 6 years (range 1-9 years). Eighty-five (84%) patients underwent
      emergency procedures. Ladd's operation was performed in all patients, with
      various additional procedures. The most frequent postoperative complications were
      adhesive intestinal obstruction, stoma necrosis, evisceration, and short bowel
      syndrome. The mortality rate was 36% in Group 1, 20% in Group 2, and 0% in Group
      3. CONCLUSIONS: In this series surgery was usually performed as an emergency
      procedure, with higher morbidity and mortality in newborns than in older infants
      and children.

PMID- 14669079
TI  - The effects of melatonin on angiogenesis and wound healing.
AB  - PURPOSE: The pineal gland hormone melatonin is a well-known neoroendocrine
      hormone. In addition to its immunomodulator effect, it also has a positive effect
      on monocyte, cytokine, and fibroblast proliferations, which also influence
      angiogenesis. This study investigated the effects of melatonin hormone on
      angiogenesis in wound healing on 100 Wistar-Albino rats. METHODS: The rats were
      divided into two groups. Melatonin dissolved in 0.9% NaCl was administered to the
      study group in a dose of 0.4 mg/kg/rat per day (0.25 cc/rat per day), and 0.9%
      NaCl to the control group in a dose of 0.25 cc/rat per day. Incisions 5 cm in
      length were made on the back skin of the rats and the wounds were closed with a
      skin stapler. Excisional biopsies from healing tissues were taken on the 3rd,
      7th, 10th, 14th, and 21st postoperative days. Angiogenesis was evaluated in
      healing tissues by light and electron microscopy and by hydroxyproline level
      measurements. RESULTS: The commencement of neovascularization and a significant
      increase ( P << 0.05) in the number of vessels were observed at all stages of the
      study group but not in the control group. The tissue hydroxyproline levels were
      also higher in the study group than in the control group. CONCLUSIONS: Melatonin
      may have a positive effect on both angiogenesis and wound healing.

PMID- 14669080
TI  - Effect of nifedipine on the healing of left colonic anastomoses in rats.
AB  - PURPOSE: Ca(2+) channel blockers inhibit collagenase production and have a
      vasodilatatory effect. They also restrict the formation of ischemia-reperfusion
      induced free oxygen radicals. The aim of this study was to assess the effect of
      nifedipine on the healing of colonic anastomoses in a rat model. METHODS: Sixty
      Wistar rats weighing 240-290 g were divided into four groups of 15 rats each: a
      3rd day control group (group A), a 3rd day treatment group (group B), a 7th day
      control group (group C), and a 7th day treatment group (group D). The treatment
      groups were given Nifedipine 3 mg/kg per day orally as three divided doses.
      RESULTS: The bursting pressure values of the anastomoses in the treatment groups
      were significantly higher than those in the control groups ( P < 0.05). The
      hydroxyproline content was also significantly higher in the treatment groups than
      in the control groups ( P < 0.05). Histologic examination confirmed that
      nifedipine treatment significantly increased collagen deposition and fibroblast
      ingrowth compared with controls ( P < 0.05). CONCLUSIONS: These results clearly
      showed that nifedipine enhanced the stability of colonic anastomoses during the
      first postoperative week.

PMID- 14669081
TI  - Breast cancer with endocrine differentiation: report of two cases showing
      different histologic patterns.
AB  - We report two cases of breast cancer with endocrine differentiation. Case 1 was a
      56-year-old woman with a 2-cm tumor in the upper outer quadrant of the right
      breast and right axillary lymphadenopathy. Excisional biopsy suggested carcinoma
      and we performed breast-conserving surgery with lymph node dissection. Histologic
      examination revealed breast cancer with endocrine differentiation resembling
      small cell carcinoma of the lung, with one nodal metastasis. Case 2 was a 71-year
      old woman with a 2.5-cm tumor in the upper outer quadrant of the right breast.
      Aspiration cytology suggested carcinoma and we performed mastectomy with lymph
      node dissection. Histologic examination revealed a carcinoid tumor, as one of the
      breast cancers with endocrine differentiation, but no nodal metastasis. The two
      patients are now disease-free 26 and 12 months after surgery, respectively.

PMID- 14669082
TI  - Positive response to oral chemoendocrine combination therapy using 5"-deoxy-5
      fluorouridine for locally advanced breast cancer with carcinomatous pleurisy:
      report of a case.
AB  - A 60-year-old postmenopausal woman presented with an ulcerating and bleeding
      tumor in her right breast. On physical examination, the tumor was found mainly in
      the D area of the right breast, and was associated with ulceration and thoracic
      rigidity. Chest X-ray showed a pleural effusion in her right chest and a computed
      tomography scan after thoracentesis showed multiple bilateral pleural nodules.
      Thus, a diagnosis of unresectable advanced breast cancer (T4cN2M1b, PLE) was
      made. She was given oral 5"-deoxy-5-fluorouridine (5"-DFUR) with
      medroxyprogesterone acetate, followed by tamoxifen, without any severe adverse
      reactions, and was subsequently followed up as an outpatient. Her tumor gradually
      decreased in size, the thoracic rigidity disappeared, and the pleural
      dissemination and effusion resolved. Thereafter, a radical mastectomy was
      performed and histologically, the tumor was Grade 1a. She had no signs of
      recurrence or metastasis 14 months postoperatively. Therefore, oral
      chemoendocrine combination therapy with 5"-DFUR resulted in a favorable quality
      of life, there were no severe adverse reactions, and the patient was able to be
      managed as an outpatient.

PMID- 14669083
TI  - Surgical management of aneurysms of the aortic arch vessels and their branches:
      report of four cases.
AB  - We review the cases of four patients with aneurysms of the aortic arch vessels
      and their branches. Two patients had a subclavian artery aneurysm, one had an
      innominate artery aneurysm, and one had a carotid artery aneurysm. We performed
      surgical reconstruction in all four patients in view of the life-threatening
      complications of these aneurysms. The approach, methods of surgical repair, and
      cerebral protection are discussed following these four case reports.

PMID- 14669084
TI  - Nonocclusive mesenteric ischemia after aorto-iliac reconstruction of a ruptured
      abdominal aortic aneurysm: report of a case.
AB  - We report a case of nonocclusive mesenteric ischemia (NOMI), which developed
      after Y-grafting for a ruptured abdominal aortic aneurysm (AAA). A 71-year-old
      man was referred to our hospital with severe abdominal pain and signs of shock.
      Computed tomography revealed a ruptured AAA, and emergency aneurysmectomy and
      aortic grafting were performed. However, on postoperative day 7, a large amount
      of pus was seen oozing from the surgical wound. An emergency laparotomy revealed
      segmental, highly diffuse necrotic changes of the small intestine, but pulsation
      of the marginal artery in the necrotic region was palpable and blood flow was
      well audible by Doppler ultrasound. These findings were consistent with a
      diagnosis of NOMI.

PMID- 14669085
TI  - Pericardiectomy to treat constrictive pericarditis in a patient with
      hyperbilirubinemia: report of a case.
AB  - An 18-year-old man was admitted to our hospital with abdominal distension and
      edema of both legs. His total serum bilirubin level was 5.2 mg/dl.
      Echocardiography showed impaired left ventricular contraction, and computed
      tomography showed a thickened pericardium with massive pleural effusion and
      ascites. Cardiac catheterization showed both a dip and a plateau in the right
      ventricle pressure curve, based on which we diagnosed constrictive pericarditis.
      The selected treatment option was a pericardiectomy. We dissected the thickened
      pericardium, which was about 7-10 mm thick, and removed as much as possible
      through a median sternotomy without cardiopulmonary bypass. Postoperatively, his
      hemodynamics and renal dysfunction improved, and the serum bilirubin level
      gradually decreased. We report this case to show how pericardiectomy was
      effective not only for improving this patient's hemodynamics, but also for
      resolving his hyperbilirubinemia. The relevant literature is reviewed following
      this case report.

PMID- 14669087
TI  - Successful laparoscopic right gastroepiploic aneurysmectomy: report of a case.
AB  - A 75-year-old woman presented with a pulsatile, movable mass, about 5 cm in
      diameter, in her lower abdomen. Abdominal ultrasonography revealed a circular
      mass with a variable hypo- and isoechoic border and a hypoechoic center. Color
      Doppler echography showed blood flow in the hypoechoic center, which was strongly
      enhanced on contrast-enhanced computed tomography. Based on these findings, we
      diagnosed a splanchnic artery aneurysm; however, celiac arteriography, performed
      twice, could not definitively identify it. An operation was performed under the
      tentative diagnosis of an aneurysm of the superior mesenteric artery or the
      gastroepiploic artery. On laparoscopic exploration, a globe-shaped mass, about 5
      cm in diameter, was found in the right side of the greater omentum, which was
      diagnosed as an aneurysm of the right gastroepiploic artery. We resected the
      aneurysm laparoscopically and the patient had an uneventful postoperative course.
      Thus, laparoscopic surgery was effective for this patient who required no
      vascular reconstruction.

PMID- 14669086
TI  - T-tube management of a major leakage of the cervical esophagogastrostomy after
      subtotal esophagectomy: report of three cases.
AB  - A major leakage of the cervical esophagogastrostomy caused by necrosis of the
      esophageal substitute was successfully managed in three patients by inserting a T
      tube. After partial necrosis of the gastric tube had been confirmed, a T-tube was
      inserted into the esophagus and the gastric tube through the reopened cervical
      wound. In one patient, a plastic esophageal prosthesis and subsequently, a
      covered self-expandable metallic stent were intubated over the fistula after T
      tube removal to prevent salivary leakage and anastomotic stenosis. In the other
      two patients, the sump tube, which had been inserted through the gastrostomy for
      decompression during surgery, was replaced with a large chest drainage tube, the
      tip of which was positioned in the esophagus, after T-tube removal. The fistula
      was closed without severe stenosis, and oral feeding was resumed on postoperative
      days 71 and 64, respectively.

PMID- 14669088
TI  - Laparoscopic distal gastrectomy for severe corrosive gastritis: report of a case.
AB  - We report a case of severe corrosive gastritis caused by alkali ingestion, which
      was successfully treated by laparoscopic gastrectomy. A 38-year-old Japanese
      woman attempted suicide by ingesting Drano. She was treated conservatively for 3
      months, but severe stenosis of the antrum secondary to scarification resulted in
      outlet obstruction. A Billroth I distal gastrectomy was performed through a
      laparoscopy-assisted approach. The patient had an uneventful postoperative course
      and was discharged on the 13th day after her operation. She was subsequently able
      to tolerate a normal diet, gained weight, and is now emotionally stable.

PMID- 14669089
TI  - Plexiform schwannoma of the small intestine: report of a case.
AB  - Plexiform schwannoma is a benign peripheral nerve sheath tumor composed
      exclusively of schwann cells arranged in a plexiform pattern. Most plexiform
      schwannomas are skin tumors and there has been only one case report of this tumor
      originating in the colon. We describe herein the first known case of plexiform
      schwannoma of the small intestine occurring without any relationship to
      schwannomatosis or neurofibromatosis. A 57-year-old man presented with a short
      history of abdominal pain, vomiting, and bloody stool after each meal.
      Jejunography demonstrated multiple nodular tumors in the small intestine. We
      resected the small intestine laparoscopically. The tumors consisted of multiple
      white nodules in the submucosal and subserosal layers. Microscopic examination
      revealed that each tumor was composed mainly of Antony A tissue, compatible with
      conventional schwannoma. Immunohistochemically, the tumors were positive for S
      100, vimentin, and neuron-specific enolase, and negative for HHF35, Alpha-SMA,
      and c-kit. No evidence of recurrence has been found in 38 months of follow-up.

PMID- 14669090
TI  - Acute small bowel obstruction secondary to ileal endometriosis: report of a case.
AB  - We report a case of acute small bowel obstruction occurring secondary to
      endometriosis of the terminal ileum. Ileal endometriosis is a rare condition that
      can cause acute small bowel obstruction. As this case and others in the
      literature highlight, establishing a preoperative diagnosis is very difficult due
      to the vagueness of symptoms and similarity in presentation to other causes of
      obstruction, and is based on a high index of suspicion. However, this disorder
      should be considered in the differential diagnosis of women of child-bearing age
      who present with symptoms of obstruction. The definitive treatment includes
      resection of the involved segment with primary anastomosis, and adjuvant hormonal
      therapy may prevent recurrence.

PMID- 14669091
TI  - Primary choriocarcinoma of the jejunum: report of a case.
AB  - We report a case of primary choriocarcinoma of the jejunum in a 45-year-old man,
      which was finally diagnosed by immunohistochemical analysis of a surgically
      resected specimen. Despite combined systemic chemotherapy, the patient died of
      progressive liver metastases 5 months after surgery. The serum human chorionic
      gonadotropin (HCG) level increased dramatically as the liver tumor progressed.
      According to our review of the 13 cases of primary or secondary choriocarcinoma
      of the small intestine reported in the English-language literature up until 2001,
      the characteristic symptoms are massive gastrointestinal bleeding and elevation
      of the serum HCG. Early diagnosis and prompt initiation of chemotherapy provide
      the only chance of improving the extremely poor prognosis associated with this
      rare neoplasm.

PMID- 14669092
TI  - Gastric outlet obstruction caused by a heterotopic pancreas in a pregnant woman:
      report of a case.
AB  - A 26-year-old Japanese woman who was 23 weeks pregnant presented with nausea,
      vomiting, and abdominal pain. Gastroduodenal endoscopic examination revealed an
      oval-shaped submucosal tumor obstructing the gastric outlet at the prepyloric
      area in the stomach. Magnetic resonance imaging showed a 5-cm cystic tumor and we
      suspected a degenerated gastrointestinal stromal tumor. No other radiological
      tests were done because of the associated risks to the fetus. Distal gastrectomy
      was performed and a histological diagnosis of heterotopic pancreas was confirmed.
      The patient had an uneventful postoperative course and was discharged 19 days
      after her operation. She delivered a healthy, full-term male infant 3 months
      later. This case of an ectopic pancreas obstructing the gastric outlet in a
      pregnant woman is reported and discussed due to its rarity.

PMID- 14669093
TI  - Prepancreatic postduodenal portal vein: report of a case.
AB  - We report an unusual case of a prepancreatic postduodenal portal vein (PPPV),
      incidentally discovered during total gastrectomy. If it had not been noticed,
      this portal vein might have been ligated and divided with disastrous
      consequences. This anomaly was not diagnosed preoperatively, but it could have
      been. Although embryological anomalies of the portal venous system, such as PPPV
      and preduodenal portal vein, are rarely encountered in abdominal surgery,
      surgeons must be aware of their possibility and be able to recognize them to
      avoid major intraoperative injury.

PMID- 14669094
TI  - Inflammatory pseudotumor of the spleen: report of a case.
AB  - We report the case of an inflammatory pseudotumor of the spleen in an
      asymptomatic 55-year-old woman, whose lesion was accidentally found and
      clinically misdiagnosed to be lymphoma. An inflammatory pseudotumor of the spleen
      was histopathologically diagnosed following a splenectomy. This lesion is a
      benign, reactive, and inflammatory process and its etiopathogenesis still remains
      elusive. The preoperative diagnosis is difficult and the optimal management of
      the asymptomastic patient with the disease is unclear. This entity should be kept
      in mind in the differential diagnosis of splenic space-occupying lesions.

PMID- 14669095
TI  - Diversity of an ectomycorrhizal fungal community studied by a root tip and total
      soil DNA approach.
AB  - Molecular methods based on soil DNA extracts are increasingly being used to study
      the fungal diversity of ectomycorrhizal (EM) fungal communities in soil. Contrary
      to EM root tip identification, the use of molecular methods enables
      identification of extramatrical mycelia in soil. To compare fungal diversity as
      determined by root tip identification and mycelial identification, six soil
      samples were analysed. Root tips were extracted from the six samples and after
      amplification, the basidiomycete diversity on the root tips was analysed by
      denaturing gradient gel electrophoresis (DGGE). The soil from the six samples was
      sieved, total soil DNA was extracted and after amplification, the basidiomycete
      diversity in the soil fractions was analysed by DGGE. Fourteen different bands
      were excised from the DGGE gel and sequenced; fungal taxon names could be
      assigned to eight bands. Out of a total of 14 fungal taxa detected in soil, 11
      fungal taxa were found on root tips, of which seven were EM fungal taxa. To
      examine whether the sieving treatment would affect EM species diversity, two
      different sieve mesh sizes were used and in addition, the organic soil fraction
      was analysed separately. DGGE analysis showed no differences in banding pattern
      for the different soil fractions. The organic fraction gave the highest DGGE band
      intensities. This work demonstrates that there is a high correspondence between
      basidiomycete diversity detected by molecular analysis of root tips and soil
      samples, irrespective of the soil fraction being analysed.

PMID- 14669096
TI  - Citrate anticoagulation in pediatric continuous venovenous hemofiltration.
AB  - Regional citrate anticoagulation has become a common alternative to systemic
      heparinization in adult continuous venovenous hemofiltration (CVVH) practice. We
      report our experience with the technique in critically ill children. We carried
      out a retrospective chart review of a 22-bed pediatric intensive care unit. CVVH
      with pre-filter citrate and systemic calcium replacement infusions was performed
      according to a strict protocol in nine consecutive critically ill children. All
      charts were reviewed for patient characteristics and CVVH circuit parameters,
      including filter survival. All complications were noted. Nurse specialists were
      interviewed about the practical management of citrate anticoagulation. All
      patient measurements of blood urea nitrogen, creatinine, sodium, ionized calcium
      (iCa), potassium, and bicarbonate were collected over the CVVH period. In seven
      patients, 12 simultaneous citrate measurements were taken from patient blood, pre
      filter blood, and hemofiltrate fluid. Nine patients (mean age 8.8+/-6.8 years)
      were treated with CVVH and regional citrate anticoagulation for 1-14 days (mean
      5.2+/-4.0 days). Of 19 filters used, 15 were replaced non-electively (mean filter
      survival 55.6+/-22.0 h). Control of azotemia and hyperkalemia was good. Sodium
      and iCa levels were well maintained. Bicarbonate levels were elevated in four
      patients without adverse effects. The mean systemic citrate level at equilibrium
      was 1.6+/-0.23 mmol/l. No systemic bleeding complications were observed. In
      children, regional citrate anticoagulation provides equivalent filter survival to
      heparin without bleeding complications. With good staff preparation, it is simple
      to perform and safe with respect to metabolic side effects.

PMID- 14669097
TI  - Muscle involvement in a patient with Henoch-Schonlein purpura nephritis.
AB  - Although Henoch-Schonlein purpura (HSP) is a small-vessel vasculitis affecting
      multiple organ systems, muscle involvement has rarely been reported. This report
      describes muscle pain and weakness in a patient with HSP nephritis (HSPN). A 13
      year-old boy suffered from purpura, abdominal pain, and symmetrical muscle pain
      and weakness of the extremities. He was diagnosed as having HSP with muscle
      involvement. His abdominal pain and muscle involvement improved 1 week after
      commencing oral prednisolone therapy. The patient subsequently developed biopsy
      proven HSPN. It should be noted that, although rare, muscle involvement might
      occur in HSP as in other systemic vasculitides. The precise pathogenic mechanism
      underlying its development is currently unclear.

PMID- 14669098
TI  - Repeat renal biopsy in children with severe idiopathic tubulointerstitial
      nephritis.
AB  - Idiopathic (primary) tubulointerstitial nephritis (TIN) of childhood is
      relatively rare. Four children, two with concomitant uveitis, aged 8-14 years,
      with idiopathic TIN who underwent repeat renal biopsy were retrospectively
      evaluated. At presentation, all had a significant elevation of the urinary
      beta(2)-microglobulin/creatinine ratio (beta2MG ratio), ranging from 10100 to
      44550, with increased histological indices of tubulointerstitial scores (TI
      scores) in excess of 6 points. Three of the children received prednisolone (PSL)
      therapy following diagnosis, while the remaining child received the therapy 30
      months after the first renal biopsy. In the children that received prompt PSL
      therapy, a rapid decrease in urinary beta2MG ratio was observed and the TI scores
      obtained at a mean interval of 16 months after the first biopsy decreased to less
      than 5, while preserving renal function. In the remaining child that received
      delayed PSL therapy, persistent elevations of urinary beta2MG ratio and TI scores
      were observed. He subsequently progressed to chronic renal insufficiency. These
      clinical findings suggest that persistent elevations of urinary beta2MG ratio and
      TI scores are indicators of progression of renal failure in TIN. For successful
      treatment, early therapeutic intervention should be deployed in selected patients
      with severe idiopathic TIN.

PMID- 14669099
TI  - Ultrasonography in the evaluation of renal scarring using DMSA scan as the gold
      standard.
AB  - Dimercaptosuccinic acid (DMSA) renal scan is presently the technique of choice
      for assessing renal scars. Recent advances suggest that ultrasonography could
      replace DMSA scan for this purpose. This paper describes the experience of a
      tertiary pediatric referral hospital performing ultrasonography and DMSA scans in
      the assessment of renal scarring. Investigations were conducted 3-6 months after
      patients presented with urinary tract infection (UTI). Results were extracted
      from the radiology information system and recorded for analysis. All children
      with a UTI who had undergone DMSA and ultrasound examination on the same day
      between January 1995 and December 1999 were included; 930 kidneys were compared.
      DMSA scan was utilized as the reference method. When used to detect focal renal
      scarring, ultrasonography had a sensitivity of 5.2%, specificity of 98.3%, a
      positive predictive value (PPV) of 50% and a negative predictive value (NPV) of
      75.8%. When used to detect diffuse renal scarring, ultrasonography had a
      sensitivity of 47.2%, specificity of 91.8%, PPV of 60.8% and NPV of 86.6%. Our
      results demonstrate that although ultrasonography has a good specificity for the
      detection of renal scarring compared with DMSA, it has low sensitivity, PPV and
      NPV. Ultrasonography cannot be substituted for DMSA scan in the evaluation of
      focal renal scarring.

PMID- 14669100
TI  - The operating room of the future: what, when and why?

PMID- 14669101
TI  - [The diagnostic process in Neurology: from clinical reasoning to assessment of
      diagnostic tests].

PMID- 14669102
TI  - [Diagnostic reasoning in neurology. An analysis of the more frequent errors].
AB  - Diagnostic reasoning is a cognitive proccess that has various performance and
      results. There are several kinds of clinical reasoning, such as model or pattern
      recognizing, causal or physiopathologic reasoning, deterministic, exhaustive, and
      hypotetic-deductive ones. Each form of reasoning may be relevant in certain
      clinical context, and all of the forms are also complementary. The logical
      consequence of diagnostic reasoning, like every cognitive proccess, is a clinical
      error. It is necessary that the neurologist knows the principles of diagnostic
      reasoning and the more frequent errors and biases. These can be summarized as:
      errors associated with the proccess of taking history and clinical examination,
      mnesic and semantic components of clinical reasoning, failure of hipotetic-
      deductive reasoning, and inadequate use of probability theory in Medicine.

PMID- 14669103
TI  - [All that neurologist would like to know about sensitivity, specificity and
      predictive values].
AB  - The aim of the diagnostic process is to establish the prevalence or probability
      of a disease given a clinical picture. A diagnostic test could be considered as
      every piece of information obtained from a patient. Diagnostic test can be done
      throughout technical devices, medical examinations or questionnaire. The
      diagnostic test offers information that allows us to classify patients according
      a different probability to be sick. The operative validity of a test can be done
      in terms of diagnostic accuracy. It means the ability to truly classify a patient
      in the right clinical situation. Diagnostic accuracy is the quality of the
      information provided by a test (sensitivity, specificity). Diagnostic usefulness
      is the practical value of the provided information. The predictive value of a
      diagnostic test depends on its accuracy and the prevalence of the disease in the
      setting where the diagnostic process is to be made. Decision making with the
      information provided by the test implies to consider the consequences of the
      false result.

PMID- 14669104
TI  - [Ethical issues of diagnostic tests in neurology].
AB  - The presence of ethical issues in the diagnostic testing process is a common
      experience in Neurology. Pacient Ls consent has often some difficulties because
      of the limited capacity of neurological patients due to cognitive impairment,
      neurological deficits or emotional disturbances. An explicit assessment of
      capacity should be performed, including the analysis of patient Ls ability to
      make complex decisions and its operational components. The consent must also
      include other ethical and legal considerations. When neurologists make the
      election of diagnostic tests, they have two obligations: being beneficent with
      their patients and using health resources properly because of distributive
      justice. Diagnostic necessities and knowledge of efficiency of tests must be
      defined in order to make beneficent and just diagnostic decisions.

PMID- 14669105
TI  - [Reflections on screening of neurological diseases].
AB  - The concepts and significance of screening and case-finding in neurological
      diseases are briefly introduced. The utility of case-finding in dementia and
      Alzheimer fs disease in primary care and in older adults is analyzed. A
      literature review of this subject and the screening data of the NEDICES study are
      discussed. It is concluded that there is no trial about this subject. For this
      reason it is not possible to recommend for or against routine screening for
      dementia in older adults in primary care. With the available evidence many
      authors recommend screening for dementia in the elderly with cognitive and
      functional decline in primary care. The Parkinson disease case-finding in primary
      care is briefly discussed. Prospective studies to investigate the screening for
      neurological diseases in primary care are a research priority.

PMID- 14669106
TI  - [Theoretical bases for the critical reading of neurological articles on
      diagnostic tests].
AB  - Neurologists usually order diagnostic tests in clinical practice. A growing
      number and sophistication of the diagnostic tests in the last decades are
      evident. It is necessary for the clinician to know the operative functioning and
      accuracy of such tools. In addition, when reading a scientific paper about
      diagnostic test, the neurologist must pay attention to some methodological
      questions. These can be summarized as: a) blind and independent comparison
      between test result and gold standard, b) adequate gold standard, c) diagnostic
      test must be applied in appropriate spectrum of the disease, d) to appraise
      possible selection bias, and e) sufficient description of methodology, so it
      allow to replicate the study. Moreover, the evaluation should include data about
      test utility, and explain risk-benefit balance for the patients in whom it is
      used.

PMID- 14669107
TI  - [Practical exercises on diagnostic test interpretation].
AB  - Although medical literature places great emphasis on therapy, diagnosis remains
      an essential part of medical practice. We present four clinical cases that show
      the interaction between pre-test probabilities and the accuracy of investigations
      (sensitivity, specificity, predictive values and likelihood ratios) The first
      example studies the influence of meningeal signs in the diagnosis of meningitis.
      The second one analyzes the diagnostic utility of investigations in patients
      suspected of dementia. The third example examines the change in the probability
      of carpal tunnel syndrome depending on the physical examination and the
      electrodiagnostic studies. The last example explains the use of ROC curves in the
      diagnosis of demyelinating disease with CSF-IgG index.

PMID- 14669108
TI  - [Hepato-biliary and pancreatic surgery].

PMID- 14669109
TI  - [Surgical therapy of hepatocellular carcinoma].
AB  - Hepatocellular carcinoma (HCC) accounts for most primary malignancies of the
      liver. The most important risk factor is liver cirrhosis. HCC can be traced by
      the tumor marker alpha-fetoprotein. Patients with a known liver cirrhosis should
      regularly be screened, including sonography and alpha-fetoprotein evaluation.
      Surgical therapy - either partial liver resection or liver transplantation - is
      the only treatment that can potentially achieve long-term survival. The presence
      of liver cirrhosis is likely to induce postoperative liver insufficiency and is
      associated with higher local tumor recurrence rate. Patients without liver
      cirrhosis or Child-Pugh A patients with tumors smaller than 5 cm may be
      considered as the ideal target group for resection. For more advanced stages of
      cirrhosis and tumors of less than 5 cm up to 7 cm in size, liver transplantation
      offers a better prognosis. Long waiting time for a suitable organ negatively
      influences liver transplantation outcome. Living donor liver transplantation is a
      novel therapeutic option that improves posttransplant survival and extends the
      indication for transplantation in hepatocellular carcinoma.

PMID- 14669110
TI  - [Systemic treatment for hepatocellular carcinoma].
AB  - Hepatocellular carcinoma (HCC) is one of the most frequent malignancies
      worldwide. A variety of pharmacological strategies has been evaluated in the
      treatment of HCC: classical chemotherapy, tamoxifen, octreotide, thymostimulin,
      pravastatin, (131)I-lipiodol as well as transarterial chemoperfusion (TAC) and
      chemoembolisation (TACE). TACE monotherapy or TACE combined with pravastatin
      resulted in a survival benefit of selected HCC patients. New strategies such as
      immunotherapy, antiangiogenic agents or cyclooxygenase inhibitors are under
      clinical investigation and might play a role in future therapies for HCC.
      Efficient strategies for the primary prevention of HCC are available and
      promising concepts in the secondary prevention have been reported.

PMID- 14669111
TI  - [Surgical treatment of colorectal liver metastases].
AB  - Resection is the only curative treatment of colorectal liver metastases proofed
      by a long-term follow-up. The operation is indicated if the metastases are
      completely removable with sufficient liver parenchyma remaining after resection
      and if the patient is fit for surgery. The resection is not indicated in cases
      with non resectable extrahepatic tumours and lymph node metastases distal the
      hepatoduodenal ligament. The postoperative mortality amounts to about 5 % and the
      5-year-survival-rates range between 20 and 40 % depending on the selection of
      patients. Aims of new concepts of operative therapy are the improvement of
      resectability by preoperative portal vein embolization, the resection combined
      with local destructive methods and preoperative chemotherapy. Additionally, new
      drugs for adjuvant treatment after resection of metastases are studied. The
      interdisciplinary discussion of the course before and after therapy is essential
      for the individual optimal treatment.

PMID- 14669112
TI  - [Percutaneous treatment of liver metastases].
AB  - Thermal coagulation therapy is a rapidly evolving technique for the treatment of
      primary and secondary hepatic tumors. Radiofrequency is gaining most of the
      attention of these techniques due to its superior effectiveness. This article
      outlines technical considerations, indications and clinical results with RF
      ablation in the liver.

PMID- 14669113
TI  - [Surgical treatment for hilar cholangiocarcinoma (Klatskin's tumor)].
AB  - Surgical treatment of hilar bile duct carcinoma remains difficult, which is due
      to the inadequate possibilities in assessing tumor extent during the preoperative
      diagnostic procedure as well as intraoperatively. Radical resection with negative
      histologic margins offers the best chance for long-term survival. The decision
      regarding the appropriate surgical approach is challenging due to the complexity
      of tumor localization and neighboring vascular structures. Aggressive resection
      demands extended liver resection, which is associated with the risk of
      postoperative liver failure. However, even limited surgery such as hilar
      resection can be curative and leads to long-term survival in individual cases.
      The principles of surgical oncology have led to more aggressive procedures,
      including the combination of liver transplantation and multivisceral resection,
      and can be performed with calculable morbidity and mortality. Nevertheless, the
      high risk of tumor recurrence under long-term immunosuppression, the limited
      availability of donor organs and the excellent results of liver transplantation
      in non-malignant diseases do not justify this procedure at present. Neoadjuvant
      radiochemotherapy has failed to demonstrate major benefit. In patients with
      irresectable tumor or distant metastases palliative measures are aimed at
      restoring an unobstructed bile flow with endoscopic placement of metal stents.
      Palliative treatment with additional radio- or photodynamic therapy may be
      considered in individual cases.

PMID- 14669114
TI  - [Endoscopic and radiological interventional therapy of benign and malignant bile
      duct stenoses].
AB  - Since the development of therapeutic endoscopic retrograde
      cholangiopancreatography and percutaneous transhepatic biliary drainage, two non
      interventional therapeutic options are available for the treatment of benign and
      malignant bile duct stenosis. Stenosis of different aetiology, which can be
      classified as benign after completion of the diagnoses, can be treated with good
      long-term dilation success in 50 to 90 % of all cases. The aim of palliative
      drainage therapy of malignant bile duct stenosis is the improvement of quality of
      life by removing the jaundice and the pruritus. In addition, the development of
      cholangitis as well as impending deterioration of the hepatic function can be
      prevented. By photodynamic therapy it seems possible to achieve an improvement of
      quality of life and of the prognosis in cholangiocarcinoma.

PMID- 14669115
TI  - [Management of bile duct injuries following laparoscopic cholecystectomy].
AB  - INTRODUCTION: The aim of the present study is to analyse our experience in the
      treatment of bile duct injury following laparoscopic cholecystectomy and to
      propose an algorithm for the management. PATIENTS AND METHODS: From January 1990
      to March 2002 175 patients with biliary tract injury sustained during
      laparoscopic cholecystectomy were treated at our institution. We divided the
      injuries into five basic types according to the mechanism, localisation and time
      of manifestation of the lesion. Risk factors affecting the outcome after
      operative repair were analysed by uni- and multivariate analysis. RESULTS: There
      were 46 patients with peripheral bile leak (Type A). Endoscopic treatment was
      successful in 92 %. 8 patients presented with an occlusion of the common bile
      duct (CBD) (Type B). Five of 6 patients with an incomplete occlusion of the CBD
      could be treated by endoscopic options. Of 52 patients that presented a lateral
      lesion of the CBD (Type C), endoscopic treatment was successful in 35 patients
      (67 %), but surgical treatment was necessary in 17 (33 %). 27 patients with a
      complete transsection of the CBD required surgical reconstruction. Endoscopic
      treatment was successful in 34 of 42 patients with a late stenosis of the CBD. 11
      of 55 patients (20 %) developed postoperative biliary complications. Univariate
      analysis identified three factors to be significant predictors of outcome: 1.
      attempts of repair before referral, 2. combined bile duct and hepatic artery
      injury, 3. Reconstruction in a situation of peritonitis. After a median follow-up
      of 44.6 months (2-109) a successful outcome was obtained in 51 of 55 (93 %)
      patients, including those requiring a secondary procedure for recurrent
      stricture. CONCLUSIONS: Peripheral leakages, small lateral lesions and short
      stenosis usually can be treated endoscopically. Extended lateral injuries,
      complete CBD transsections and long stenoses require surgical therapy. For a
      successful therapy a specialized multidisciplinary team is crucial.

PMID- 14669116
TI  - [Reconstruction of bile duct lesions by an autologous vein graft and a bio
      degradable endoluminal stent in an animal model: technique and clinical impact].
AB  - INTRODUCTION: In this study a new treatment of bile duct lesions was
      investigated. A segment of the bile duct was replaced by an autologous venous
      interponate which had been endoluminally stented with a braided bio-degradable
      stent. METHODS: A total of 18 pigs (20-28 kg) was divided into three equal groups
      (I-III). In each group a 2 cm segment of the jugular vein was harvested. The
      animals in Group I (vein group, n = 6) underwent resection of a 2 cm long segment
      of the common bile duct which was replaced solely by the venous interponate, in
      Group II (stent group, n = 6) the venous interponate had been endoluminally
      stented by a braided bio-degradable stent. Group III (control group, n = 6)
      underwent only a circular mobilization of the common bile duct. Postoperatively
      survival rate, general condition as well as the weight were observed and checked
      for 6 months. During surgery and finally after sacrifice after 6 months blood and
      tissue samples were taken and semiquantitatively scored concerning grade of
      inflammation and fibrosis. RESULTS: In the stent and control group all animals
      survived in good condition. 3 pigs of the vein group died within 3 weeks showing
      signs of biliary peritonitis, another one died due to a high grade stenosis of
      the common bile duct with secondary biliary cirrhosis after 4 months. In the
      stent group all animals survived until sacrifice after 6 months. On examination
      the venous interponate was laminated with bile duct epithelium showing the
      diameter of the implanted stent. CONCLUSION: The reconstruction of bile duct
      lesions by a venous interponate in combination with a bio-degradable stent is
      easy to perform and represents a clinically interesting alternative to the
      biliodigestive anastomosis because of the preservation of the sphincter oddi.
      After 6 months the stent is completely absorbed and the venous interponate is
      laminated with bile duct epithelium.

PMID- 14669117
TI  - [Surgical anatomy of main intrahepatic portal tracts].
AB  - The aim of the study was the identification of anatomical characteristics of
      lymphobiliary interactions and their presumed connections in the intrahepatic
      portal tracts. Morphological investigation of vascular-fibrous structures in the
      intrahepatic portal tracts of 75 adults liver samples was performed. It was
      described that the single segments of the intrahepatic structures and their
      fibrous tunics constitute of three vascular-fibrous sheathes orbiculary
      surrounding each other. The extramural biliary mucous glands provide the
      connections between the lymphatic and intrahepatic biliary systems.

PMID- 14669118
TI  - [Perioperative risk assessment in surgery - an analysis in 10 395 patients].
AB  - The aim of this study was to perform a risk analysis on the basis of routinely
      documented variables (age, sex, ASA-classification, priority of operation,
      malignant disease, intraperitoneal or intrathoracic operation and duration of
      operation) to identify surgical patients who benefit from a more complex risk
      assessment. PATIENTS AND METHODS: In a prospective observational trial we
      analysed a consecutive series of 10 395 patients who were operated on in our
      General Surgical Department from January 1996 until December 2000 in respect to
      in-hospital mortality. The variables were examined in univariate tests. Factors
      with significant impact were subsequently included in a multiple logistic
      regression analysis. This was done for all variables and afterwards for each ASA
      class separately. Predictive accuracy of the prediction model was calculated by
      the area under a receiver operating characteristic curve (AUC (ROC)). RESULTS:
      The overall mortality was 3.9 %. For ASA-classes 2 to 4 we were able to establish
      a prediction model by means of multiple logistic regression that identified ASA
      classification (Odds Ratio [OR ] ASA-class 3 = 3.7; OR ASA-class 4 = 22.4), age
      (OR 1.019 per year), duration of operation (OR for duration > or = 240 min =
      2.25), intraperitoneal/intrathoracic operation (OR = 4.6), emergency operation
      (OR = 3.1), and malignant disease (OR = 1.5) as independent predictive factors.
      Both risk group 1 and risk group 5 were excluded from the analysis because there
      was no mortality in risk group 1 and too few patients in risk group 5. We found
      an AUC (ROC) of 91.6 % for the considered ASA-classes. CONCLUSION: The ASA
      classification is a good instrument for the assessment of perioperative
      mortality. Its predictive power can substantially be improved in the classes 2 to
      4 by the variables age, duration of operation, intraperitoneal or intrathoracic
      operation, priority of operation, and malignant disease.

PMID- 14669119
TI  - [Does Charlson-comorbidity index correlate with short-term outcome in patients
      with gastric cancer?].
AB  - OBJECTIVES: Because of the high prevalence of coexisting medical conditions in
      patients with gastrointestinal cancer, clinical investigators often need to
      adjust for comorbidity when assessing the effect of comorbidity on patient
      outcome. Comorbidity in cancer has been shown to be a major determinant in
      treatment selection and survival. However, none of the comorbidity studies in
      patients with gastric cancer reported in the literature have been performed using
      the Charlson comorbidity index. The purpose of this study was to examine the
      applicability of the CCI and usefulness of the CCI as a predictor in patients
      with gastric cancer and to examine whether it correlates with short- term outcome
      in these patients. METHOD: Study design was a prospective study. The study
      population was drawn from our department and included 139 patients who underwent
      curative treatment of gastric cancer between 1.1.1997 and 31.12.2001. All
      patients were staged by the CCI for comorbidity and divided into three groups
      based on the comorbidity severity staging. Group 1 included patients with no
      comorbidity, group 2 included those with low-level comorbidity and group 3 those
      with severe comorbidity. Outcomes were compared based on these divisions
      performing uni- and multivariate analysis. RESULTS: 35 patients (25.2 %) had no,
      55 (39.6 %) low and 39 (35.2 %) severe comorbidity. 28.8 % of patients showed no
      or mild, 14.4 % moderate and 14.4 % of patients severe postoperative
      complications and 5.8 % died in hospital postoperatively. 30-day-mortality was
      3.6 % (n = 5). There was no statistical significant correlation between CCI and
      occurrence of postoperative complications, severity of postoperative course and
      postoperative stay in hospital. In multivariate analysis only age was an
      independent factor for postoperative course. CONCLUSION: The method of
      classifying comorbidity by CCI provides a simple, readily applicable and valid
      method of estimating risk of death from comorbid disease for use in longitudinal
      studies and in outcomes research from administrative databases. In gastric
      cancer, however, the CCI was found not to be a valid prognostic indicator.

PMID- 14669120
TI  - [Intralobar pulmonary sequestration].
AB  - Sequestration is defined as an area of abnormal pulmonary tissue not connected
      with the bronchial tree, supplied by an aberrant systemic artery and without a
      normal pulmonary function. Extralobar (ELS) and intralobar (ILS) forms are
      distinguished. During the year 2002 the authors diagnosed and operated upon two
      cases of the intralobar form of pulmonary sequestration, and in last 25 years
      five cases - 4 x ILS and 1 x ELS. Reported are a 35 year old man with relapsing
      infections of the sequester and a 21 year old woman where the sequestration was
      accidentally found without clinical symptoms. The focus was localized in both
      cases in the left lower lobe of the lungs, anomalous supply arteries derived from
      the thoracic aorta. Venous drainage of the sequester was different - in the man a
      systemic drainage via the v. azygos, in the woman via the pulmonary veins was
      found. In one case the diagnosis was made on the basis of angiography and
      computer tomography, in the other case it was made on the basis of multidetector
      CT angiography (MDCTA). Both findings were treated by primary surgical
      intervention lobectomy. The postoperative course was uneventful.

PMID- 14669121
TI  - [Life-threatening complication of the Nuss-procedure for funnel chest. A case
      report].
AB  - This report is the first description of an additional major complication seen
      with the Nuss repair. In addition to the conventional Rehbein and Ravitch
      operations for funnel chest, the minimally invasive procedure developed by Nuss
      has recently been added to the therapeutic options. The present report describes
      the case of a 21-year-old man who underwent a Nuss repair with implantation of 2
      pectus bars 4 months previously. During the primary operation the central tendon
      of the left diaphragm was unnoticed injured. We performed an emergency operation
      on the patient to repair an incarcerated diaphragmatic hernia. The thorax was
      found to contain not only the entire, twisted stomach, but also the transverse
      colon and the spleen. During induction of anaesthesia the patient suffered a
      cardiovascular collapse. After successful resuscitation, thoraco-abdominal
      surgery was performed and the diaphragm closed from the thoracic side. Other
      authors have also reported major life-threatening complications of the Nuss
      procedure, such as perforation of the heart. A careful evaluation of this
      procedure and the establishment of clear indications taking the age of the
      patient, the thoracic deformity and connective tissue disease into account, are
      mandatory to avoid discredit of this method.

PMID- 14669122
TI  - [Massive localized lymphedema - a rare entity].
AB  - Massive localized lymphedema is a rare disease. Only a few cases have been
      described in the literature. These monstrous pseudotumors of the subcutis are
      mostly localized in the inguinal region or at the lower extremity. These tumors
      often show a slow growth for many years. Besides hernias, lipomatous tumors must
      be distinguished. The therapy of choice is the excision of the tumor. Relapse is
      not uncommon in the few cases described in the literature so far. The diagnostic
      procedure and therapy of an 48-year-old women with a massive localized lymphedema
      weighing about 22 kg are demonstrated and discussed.

PMID- 14669123
TI  - Myoblasts for survive 16 weeks after intracardiac transfer and start
      differentiation.
AB  - INTRODUCTION: Skeletal myoblasts have been shown to survive transfer into
      myocardial scar tissue. The purpose of this study was to investigate
      differentiation after intramyocardial transplantation. Additionally, we evaluated
      an intravital fluorescence dye. MATERIALS AND METHODS: Skeletal myoblasts were
      harvested from 8 male inbred Lewis rats and expanded in culture. For each
      transplantation planned, 10(6) cells were trypsinized and incubated for three
      minutes with 2 ml of buffered PKH-26 solution (Sigma, St. Louis). This dye was
      integrated into the cell membrane. After washing three times, the cells were
      plated again for two more days. The cells were then transplanted into the hearts
      of 60 female Lewis-rats, mean weight 380 g (260 - 450 g). At implantation, 10(6)
      cells suspended in 100 microliters were injected into the apex region of the left
      ventricle. 12 animals served as the control group with only cell medium injected.
      Animals were sacrificed after 1, 2, 6, 8, 12, and 16 weeks (n = 10 each). The
      hearts were explanted and serial frozen sections of the hearts were prepared for
      detecting labeled cells. Sections with labeled cells were stained
      immunohistochemically for Myo D1 (myogenic origin), n-cam (early myotubes),
      desmin (muscular filament), myosin light chain (muscular contractile protein),
      and connexin 43 (tight junction). RESULTS: Cell labeling was successful in all
      cases. After two days, the myoblasts had recovered from the staining procedure.
      The fluorescing dye, however, was only rarely transmitted by cell division.
      Marked cells were found in the intercellular spaces between the cardiac myofibers
      in at least 8 animals from each group. No fibrotic reaction or inflammation was
      seen surrounding the transplanted cells. Up to 6 weeks after implantation, the
      cells stained positive for n-cam and Myo D1, and particularly for desmin. More n
      cam positive cells were found than labeled cells, indicating cell division after
      the cell transfer. Two animals suffered sudden death after a follow-up time of 8
      and 10 weeks, which was possibly due to cardiac arrhythmia. After 8 weeks, the
      cells formed conglomerates and stained positive for desmin, myosin light chain,
      and connexin 43. The cells were not structurally integrated into the recipient
      myocardial tissue, however. CONCLUSIONS: Myoblasts divided further after
      transplantation into rat myocardium. Positive staining for desmin demonstrated
      the development of myofibers. Starting at 8 weeks after transplantation, the
      cells started differentiation without reaching structural integration during
      follow-up. Labeling the cells with PKH-26 proved to be a reliable method to
      detect the cells.

PMID- 14669124
TI  - Cardiopulmonary bypass impairs left ventricular function determined by
      conductance catheter measurement.
AB  - OBJECTIVE: Postoperative cardiac depression is attributed to ischemia and the
      effects of cardiopulmonary bypass (CPB). To evaluate the effect of CPB alone on
      postoperative left ventricular (LV) dysfunction, we used a conductance catheter
      to determine the LV performance by pressure-volume relation before and after CPB.
      METHODS: Twenty-two 3-week-old piglets underwent sternotomy and normothermic CPB
      for one hour. A conductance catheter was placed in the LV cavity. End-systolic
      pressure-volume relationships (ESPVR), left ventricular end-diastolic pressure
      (LVEDP) and systemic vascular resistance (SVR) were measured under steady-state
      conditions before and 15 min after weaning from CPB in group A (n = 11). Group B
      included 11 piglets without CPB and served as control. RESULTS: There was no
      difference between groups before initiating CPB. As an indication of depressed LV
      function, the ESPVR slope (mmHg/ml) was significantly lower in group A after
      weaning from CPB than in group B (1.69 +/- 0.5 vs. 1.86 +/- 0.55; p = 0.008). In
      group A, peak dP/dt (max index) (mmHg/s/m (2)) decreased markedly (1596 +/- 339
      vs. 2045 +/- 206; p = 0.03), while LVEDP (mmHg) was significantly increased (11.7
      +/- 2.6 vs. 5.4 +/- 0.9; p < 0.0001). In addition, SVR (index) (dyn x s x cm (
      5)/m (2)) in group A was significantly lower (1407 +/- 176 vs. 1677 +/- 313; p <
      0.0001) than in group B. CONCLUSION: Using the very sensitive conductance
      catheter technique in a pig model, we could show that CPB leads to a significant
      depression of LV contractility and elastance even without ischemic arrest.

PMID- 14669125
TI  - Adequacy of perfusion during hypothermia: regional distribution of
      cardiopulmonary bypass flow, mixed venous and regional venous oxygen saturation -
      hypothermia and distribution of flow and oxygen.
AB  - BACKGROUND: Hypothermia during CPB is used to reduce metabolic activity, thus
      protecting organs and tissues. The aim of this study was to investigate the
      relationship between regional and mixed venous oxygen saturation and distribution
      of pump flow with respect to hypothermia. METHODS: Twenty-five patients
      undergoing a Ross procedure were included in a prospective, controlled study.
      During standard CPB, temperature was reduced stepwise to 28 degrees C. Blood
      gases (a-stat regimen) were analysed in samples from the inferior (IVC) and the
      superior vena cava (SVC), arterial and mixed venous blood. Flow was detected
      separately in the SVC, IVC, arterial, and collecting venous line. Samples were
      taken, and flows were measured before CPB, during hypothermia, during rewarming,
      and 30 min after CPB discontinuation. RESULTS: Oxygen saturation in the IVC was
      lower than in the SVC and in mixed venous blood at all times (max. difference -
      17.3 +/- 3.0 % during hypothermia, - 23.8 +/- 2.9 % during rewarming, p < 0.01).
      There was a statistical correlation of mixed and IVC venous oxygen saturation (r
      = 0.79, p < 0.001) but not of SVC venous blood. Hypothermia had a major influence
      on pump flow distribution as backflow from the SVC decreased significantly in
      favour of IVC flow with increasing degree of hypothermia (increase of flow
      difference from 1.15 +/- 0.23 l/min to 1.49 +/- 0.36 l/min, p < 0.01).
      Temperature profiles were similar when detected in aorta, pulmonary artery,
      tympanum and nasopharygeum, but differed significantly from other sites.
      CONCLUSIONS: During hypothermic CPB, regional deoxygenation occurs in spite of
      normal mixed venous saturation. The level of hypothermia has a major impact on
      bypass flow distribution with cerebral perfusion reduction. Methods of regional
      oxygenation assessment are needed, and altered strategies during hypothermia have
      to be taken into consideration.

PMID- 14669126
TI  - Initial experiences with the Impella device in patients with cardiogenic shock -
      Impella support for cardiogenic shock.
AB  - BACKGROUND: We planned a study to assess the safety, feasibility, and efficacy of
      the Impella micro-axial blood pump in patients with cardiogenic shock. METHODS:
      From January 2001 to September 2002 inclusive, 16 patients in cardiogenic shock
      (maximal inotropic support and with IABP in 11 cases) underwent left ventricle
      unloading with the Impella pump. 6 were placed via the femoral artery (patients
      in the coronary care unit) and 10 directly through the aorta (postcardiotomy
      heart failure). In three patients, the device was used in combination with ECMO.
      Mean age was 60 years (range 43 - 75), 11 were male. RESULTS: A stable pump flow
      of 4.24 +/- 0.28 l/min was reached (3.3 +/- 1.9 l/min in patients with ECMO and
      Impella). Mean blood pressure before Impella) support was 57.4 +/- 13 mmHg, which
      increased to 74.9 +/- 13 mmHg after 6 hours and 80.6 +/- 17 mmHg (p = 0.003)
      after 24 hours. Cardiac output increased from 4.1 +/- 1.3 l/min to 5.5 +/- 1.3 (p
      = 0.003) and 5.9 +/-1.9 l/min (p = 0.01) at 6 and 24 hours. Mean pulmonary wedge
      pressure decreased from 29 +/- 10 mmHg to 17 +/- 5 mmHg and 18 +/- 7 mmHg at 6 (p
      = 0.04) and 24 hours. Blood lactate levels decreased significantly after 6 hours
      of support (from 2.7 +/- 1 to 1.3 +/- 0.5 mmol/l, p = 0.004). Device-related
      complications included three sensor failures (no clinical action), one pump
      displacement (replacement) and six incidences of haemolysis (peak free plasma
      haemoglobin > 100 mg/dl, no clinical action). Eleven patients (68 %) were weaned,
      six (37 %) survived. CONCLUSIONS: Left ventricular unloading with the Impella
      pump via the transthoracic or femoral approach is feasible and safe. Support led
      to a decrease in pulmonary capillary wedge pressure, increase in cardiac output
      and mean blood pressure, and improved organ perfusion in patients with severe
      cardiogenic shock.

PMID- 14669127
TI  - Five-year follow-up after long plaque-bridging coronary arteriotomy for diffuse
      coronary artery disease.
AB  - Long arteriotomy bridging a stenotic plaque or segment may improve runoff in
      diffuse coronary artery disease. However, patency might be impaired due to
      vascular wall pathology. OBJECTIVE: To determine the patency rates of plaque
      bridging arteriotomy compared to conventional coronary artery bypass grafting.
      METHODS: Between May 1995 and December 1998, 104 patients with a mean age of 65
      +/- 7 years received a long arteriotomy extending over a heavily plaqued area in
      an effort to treat their diffuse coronary artery disease. The length of the
      arteriotomy ranged from 14 mm to 40 mm. We retrospectively analyzed the intra
      individual bypass graft patency rates by multidetector-computed tomography or
      coronary angiography. RESULTS: The mean follow-up was 5 years. There were 5 (4.8
      %) early and 10 (9.6 %) late deaths, three non-cardiovascular. Graft patency for
      internal thoracic artery (ITA) to left anterior descending artery (LAD) (plaque
      bridging) was 94.8 %, for saphenous vein graft (SVG) to circumflex artery (CX)
      (plaque-bridging) 67 %, and SVG to right coronary artery (RCA) (plaque-bridging)
      79.5 %. Graft patency for ITA to LAD (conventional) was 94.9 %, for SVG to CX
      (conventional) 72.4 %, and SVG to RCA (conventional) 75 %. Freedom from angina
      was 82.8 % (n = 58/70), freedom from myocardial infarction was 95.7 % (n =
      67/70), freedom from reintervention was 91.4 % (n = 64/70) and freedom from
      reoperation was 100 % (n = 70/70). CONCLUSION: Diffuse coronary artery disease
      can be treated by extending the arteriotomy over the plaques, with graft patency
      rates comparable to bypass grafts onto less diseased segments.

PMID- 14669128
TI  - Procalcitonin is a valuable prognostic marker in cardiac surgery but not specific
      for infection.
AB  - BACKGROUND: The prognostic value of elevated serum levels of procalcitonin (PCT)
      in patients early after cardiac surgery on cardiopulmonary bypass (CPB) remains
      unclear. In a prospective study, we investigated whether PCT is useful as a
      prognostic marker in cardiac surgery with respect to mortality, complications and
      infections, and whether PCT is a specific marker for occurrence of infections.
      METHODS: Within 8 months, a subset of 80 high-risk patients (APACHE II-score:
      25.1 +/- 4.7 (mean +/- SD)) out of a consecutive cohort of 776 patients was
      investigated. Demographic data, operative data and clinical endpoints (mortality,
      infection, severe complication) were documented. Serum levels of PCT were
      analyzed preoperatively and at postoperative day 1. RESULTS: Hospital mortality
      in this high-risk group was 21.3 %, infections occurred in 33.8 % and
      complications in 58.8 % of the patients. Preoperative PCT was normal in all
      patients. Postoperative PCT was increased in non-survivors compared to survivors
      (34.3 +/- 7.0 ng/ml vs. 15.9 +/- 4.9 ng/ml; p < 0.05), in patients with severe
      complications (30.3 +/- 6.7 ng/ml vs. 5.5 +/- 1.4 ng/ml; p < 0.05) and in
      patients with infections (38.4 +/- 11.3 ng/ml vs. 10.8 +/- 1.6 ng/ml; p < 0.05).
      Area under receiver operating characteristic curve for PCT as predictor of
      mortality, infections and complications was 0.772 (95 %-confidence-interval (CI):
      0.651 - 0.894), 0.720 (95 %-CI: 0.603 - 0.837) and 0.861 (95 %-CI: 0.779 -
      0.943), respectively. PCT was not different with infectious compared to non
      infectious complications. CONCLUSIONS: High levels of PCT are associated with
      mortality, infections, and severe complications early after cardiac surgery using
      cardiopulmonary bypass and therefore provide a valuable prognostic marker.
      However, PCT does not discriminate between infectious and non-infectious
      complications.

PMID- 14669129
TI  - Concept for diagnosis and therapy of unilateral recurrent laryngeal nerve
      paralysis following thoracic surgery.
AB  - BACKGROUND: Injury to the recurrent laryngeal nerve is a potential complication
      in thoracic surgery, and may lead to postoperative dysfunction due to the
      resulting insufficient glottal closure. The aim of this study was, first, to
      develop an interdisciplinary concept of early diagnosis and adequate therapy of
      recurrent laryngeal nerve paralysis (RLNP), and second, to investigate efficiency
      of this approach. METHODS: 120 patients (77 male, 43 female) aged between 15 and
      85 years (mean 57 years) were examined otolaryngologically before and after
      thoracic surgery. Individual therapeutic modalities were chosen according to
      established criteria. RESULTS: In 18 patients (15 %), RLNP was found (16 left, 2
      right). Five had already been diagnosed preoperatively. Functional voice therapy,
      stimulation-current therapy or external vocal fold medialization was performed
      depending on the prognostic criteria. CONCLUSIONS: RLNP following thoracic
      surgery requires immediate diagnosis and therapeutic strategy to minimize
      postoperative complications and to overcome impairments in the voice, swallowing,
      and coughing. The interdisciplinary concept presented in this study is especially
      advisable in high-risk RLNP procedures.

PMID- 14669130
TI  - Non-small-cell superior sulcus tumor: results of en bloc resection in fifty-six
      patients - non-small-cell pancoast.
AB  - BACKGROUND: Various multidisciplinary approaches are taken in the treatment of
      superior sulcus tumors. The purpose of this study was to determine the outcome,
      long-term results, and factors associated with prolonged survival after
      administering different combined radiosurgical regimens in a single institution.
      METHODS: Between 1986 and 2000, 56 patients (43 men, 13 women) with superior
      sulcus tumor and histology of non-small-cell lung cancer underwent surgical
      resection. There were four treatment groups: I - preoperative radiation and
      operation (n = 15); II - preoperative radiation, operation and postoperative
      radiation (n = 22); III - operation and postoperative radiation (n = 10) and IV -
      no radiotherapy (n = 9). Survival was calculated by the Kaplan-Meier method and
      prognostic factors were assessed for significance by log-rank test and Cox
      regression analysis. RESULTS: The five-year survival rate after complete
      resection and N0/1 was 34 %. Of the prognostic factors analyzed, the histology,
      type of irradiation regimen and Horner's syndrome did not influence survival.
      Completeness of resection and mediastinal lymph node involvement clearly
      influences survival in univariate analysis. Age, sex and TNM classification were
      found to be independent significant prognostic factors for survival following
      resection. CONCLUSION: With superior sulcus tumors, every attempt should be made
      to resect the tumor completely by en bloc chest-wall resection with lobectomy and
      systematic hilar and mediastinal lymph node dissection. Mediastinal exploration
      by routine mediastinoscopy is recommended for identification of patients with
      advanced nodal involvement. Long-term survival may be relative to care taken in
      patient selection and extent of the resection performed. No significant
      difference in survival of patients with different irradiation regimens could be
      demonstrated in this study.

PMID- 14669131
TI  - Treatment of post-pneumonic empyema thoracis.
AB  - OBJECTIVE: The present study evaluates the management of 65 consecutive patients
      with post-pneumonic empyema thoracis (PET) treated in our department during the
      last ten years. MATERIALS: There were 51 male (78.5 %) and 14 female (21.5 %)
      aged 23 - 82 years. The initial cause of PET was pneumonia (postoperative and
      posttraumatic empyemas were excluded). In 2 cases, a bronchopleural fistula
      coexisted. Diagnosis was based on clinical, radiological and pleural fluid
      culture findings. Pneumonococci and staphylococci were the predominant bacterial
      isolates in our series. RESULTS: Tube thoracostomy drainage (TS) was performed in
      all our patients. Forty-nine patients (75.4 %) were successfully treated with TS
      alone. The other 16 patients were submitted to thoracotomy: lung decortication (n
      = 14) along with segmentectomy in two cases and the Eloesser procedure, also in
      two cases. The mortality rate reached 9.2 % (n = 6). Septic shock, multiple organ
      failure, cardiac insufficiency, and end-stage renal failure were the causes.
      CONCLUSIONS: 1. Complete drainage and full lung expansion by tube thoracostomy
      with suction are essential in the management of post-pneumonic empyema thoracis.
      Surgery should only be carried out right away if these conditions are not
      achieved. 2. Despite clinical experience and the major strategies and procedures
      available, the mortality remains high.

PMID- 14669132
TI  - Chylothorax: a complication following lung resection in patients with NSCLC -
      chylothorax following lung resection.
AB  - BACKGROUND: Chylothorax following lung resection is not as rare as a
      postoperative complication as previously reported due to systematic lymph node
      dissection in patients undergoing lung resection for NSCLC. METHODS: We
      retrospectively reviewed our cases that had undergone lung resection for NSCLC
      and investigated the frequency and outcome of chylothorax in these patients. The
      factors investigated were the site and type resection, technique of systematic
      lymph node dissection, tumour histology and disease stage. RESULTS: Seven of 673
      patients that had undergone lung resection were complicated by chylothorax (1.04
      %), following lobectomy in 5 (1.28 %) and pneumonectomy in 2 (0.7 %) (p = 0.36).
      The fistula closed spontaneously in 5 patients between 4 - 17 days
      postoperatively (71 %). One of the patients in the conservative management group
      died on the 28th day postoperatively due to pneumonia (14 %). The remaining 2
      patients underwent rethoracotomy on the 5th and 6th days. CONCLUSIONS: These
      results suggest that the site of operation, type resection, and technique of
      systematic nodal dissection, tumour histology and disease stage do not influence
      the development of chylothorax in patients with NSCLC. The chylous fistula
      following lung resection for NSCLC tends to close spontaneously.

PMID- 14669133
TI  - Ruptured intercostal artery pseudoaneurysm after blunt thoracic trauma.
AB  - Here, we present the case of ruptured intercostal artery pseudoaneurysm two
      months after blunt thoracic trauma. Ruptured aneurysm hemorrhaged into the
      retroperitoneal space due to adhesion in the intrathoracic space. We
      unsuccessfully embolized the aneurysm during an angiographic procedure and
      performed the aneurysmectomy, removing the hematoma, using a retroperitoneal
      approach. Ruptured intercostal artery pseudoaneurysm after blunt thoracic trauma
      may have caused the delayed life-threatening hemorrhage.

PMID- 14669134
TI  - Left atrial thrombus mistaken as a tumor after heart transplantation.
AB  - The occurrence of neoplastic malignancy due to chronic immunosuppression in heart
      transplant recipients is a well-known threat. Continuous check-ups are therefore
      mandatory in this patient group. We describe the case of a 58-year-old man
      transplanted for dilated cardiomyopathy. During regular diagnostic check-up, a
      solid mass in the left atrium was discovered on the transesophageal
      echocardiogram. Since the mass became progressively larger over three years and
      showed features of neither myxoma nor thrombus, a cardiac sarcoma was suspected.
      A secondary diagnostic magnetic resonance tomography (MRT) investigation was
      contraindicated due to an implanted pacemaker. Intraoperatively, the mass proved
      to be an organized thrombus. Surgery had to be performed without an established
      accurate diagnosis due to a suspected malignancy in chronically immunosuppressed
      patients.

PMID- 14669135
TI  - Obstructed coarctation in a right aortic arch in an adult female.
AB  - Coarctation of a right aortic arch is rare congenital anomaly. We report a rare
      case of a 24-year-old female with coarctation of the right aortic arch with
      aberrant left subclavian artery between the right common carotid and right
      subclavian arteries. The coarctation progressed into complete obstruction as the
      interruption of the aorta in adulthood. To prevent cerebral complications and
      progression to heart failure, surgical procedure was selected. Extraanatomical
      bypass grafting between the ascending and descending aorta was successfully
      performed using cardiopulmonary bypass. Some patients diagnosed with interruption
      of the aortic arch in adulthood might be displaying progression of undiagnosed
      coarctation, as our in case. Three-dimensional computed tomography was useful to
      detect the obstructive lesion and to determine the surgical approach and methods.

PMID- 14669137
TI  - [Experience in the treatment of multiple sclerosis with interferon beta in
      Galicia].
AB  - OBJECTIVE: To analyze the experience in daily clinical practice of interferon
      beta (IFN-beta) treatment in relapsing-remitting (RR) and secondary progressive
      (SP) multiple sclerosis (MS) in Galicia (Spain). PATIENTS AND METHODS: Patients
      with RR-MS and SP-MS treated with IFN-beta1a and 1b between 1995 and
      December/2000, analyzing demographic and clinical data. RESULTS: 313 patients
      were included, with a mean age of 38.2 years. A total of 296 patients (94.6%)
      were clinically defined MS and 17 (5.4%) were laboratory supported (Poser
      criteria); 84.6% of the patients were RR and 15.4% were SP. The mean duration of
      the disease prior to treatment was 7.06 years. Betaferon was used in 52.4%
      patients (115 RR-MS and 47 SP-MS), Avonex in 26% and Rebif in 21.6%. Relapse rate
      was reduced in 68.8% for the RR-MS for Betaferon-treated patients, 73.3% for
      Avonex treated and 35.7% for Rebif-treated patients. Betaferon reduced relapse
      rate in 50% for SP-MS. The global EDSS remained stable during IFN-beta treatment.
      During treatment, 33% of Betaferon, 60.5% of Avonex and 54.5% of Rebif-treated
      patients remained relapse-free. Treatment was suspended in 12.9% of Betaferon,
      6.2% of Avonex, and 3% Rebif-treated patients. The most frequent causes of
      treatment suspension were increase in disability and in relapse count.
      CONCLUSIONS: The present study supports the benefits of IFN-beta treatment in RR
      MS and SP MS in daily clinical practice, with reduction in relapses count and
      incapacity, good over-all tolerance and low incidence of serious adverse side
      effects.

PMID- 14669136
TI  - Mapping multiple sclerosis susceptibility to the HLA-DR locus in African
      Americans.
AB  - An underlying complex genetic susceptibility exists in multiple sclerosis (MS),
      and an association with the HLA-DRB1*1501-DQB1*0602 haplotype has been repeatedly
      demonstrated in high-risk (northern European) populations. It is unknown whether
      the effect is explained by the HLA-DRB1 or the HLA-DQB1 gene within the
      susceptibility haplotype, which are in strong linkage disequilibrium (LD).
      African populations are characterized by greater haplotypic diversity and
      distinct patterns of LD compared with northern Europeans. To better localize the
      HLA gene responsible for MS susceptibility, case-control and family-based
      association studies were performed for DRB1 and DQB1 loci in a large and well
      characterized African American data set. A selective association with HLA-DRB1*15
      was revealed, indicating a primary role for the DRB1 locus in MS independent of
      DQB1*0602. This finding is unlikely to be solely explained by admixture, since a
      substantial proportion of the susceptibility chromosomes from African American
      patients with MS displayed haplotypes consistent with an African origin.

PMID- 14669138
TI  - [Effectiveness and tolerability of levetiracetam in 43 children and adolescents
      with epilepsy].
AB  - INTRODUCTION: Levetiracetam (LEV) is the latest antiepileptic drug (AED) to be
      marketed, and is indicated for use in association in adults with focal seizures.
      AIMS: The purpose of this study is to report on our experience of administering
      LEV to children and adolescents with pharmacoresistant epilepsies. PATIENTS AND
      METHODS: Retrospective open trial involving the observation of 43 children and
      adolescents with refractory epilepsies, using associated LEV for more than 6
      months on an individual basis, the aim of which was to evaluate the repercussions
      on the frequency of the seizures, together with the adverse and beneficial side
      effects of LEV administration. RESULTS: With mean doses of LEV of 45.01 +/- 33.02
      mg/kg/day the frequency of seizures was reduced by >50% in 65% of patients, while
      seizures were completely eradicated in 14% of patients; adverse side effects were
      reported in 28% of patients, although these were usually transient or tolerable,
      as LEV administration only had to be stopped for this reason in two cases
      (4.65%). Relatives noted an improvement in social behaviour and in cognitive
      skills in the case of 15 children (34.9%). CONCLUSIONS: 1. LEV is an effective
      drug that is well tolerated in children and adolescents with refractory
      epilepsies; 2. Its effectiveness in different types of seizures suggests a broad
      therapeutic spectrum; 3. LEV is a well tolerated drug with favourable side
      effects, a fact that is rarely reported with regard to other AED.

PMID- 14669139
TI  - [The neurological diagnoses in the preadoptive medical records from Russia].
AB  - INTRODUCTION: Russia is the second country of origin of the adopted foreign
      children in Spain. The Russian preadoptive medical records offer a little and
      confused information. OBJECTIVE: In a series of preadoptive medical records from
      Russia to analyze the emitted neurological diagnoses in the newborn period and
      its relation with perinatal data and formulated neurological diagnoses to the
      date of its elaboration. MATERIALS AND METHODS: Seventy-two records submitted to
      a consultant from August 1999 to August 2003 were reviewed. Demographic,
      perinatal data and neurological diagnoses were compiled, making comparative
      statistical study. RESULTS: The mean age (SD) of the children (86.1% male) was of
      21.5 (12.1) months. All the analyzed perinatal data were described in only 15.3%
      of the records. The number of neurological diagnoses in the newborn period was
      higher when histories of Apgar score < or =6-7 (1.7:1), 'perinatal encephalopathy
      of hypoxic, ischemic and/or traumatic origin' (1.6:1), maternal health problem
      during the gestation (1.3:1), gestational age < or =37 weeks (1.2:1),
      intrauterine growth delay and/or low weight (1.2:1) were described, and when
      diagnoses of psychomotor development delay (1.6:1) and microcephaly (1.2:1) to
      the emission of the report were formulated, although statistically significant
      differences were not observed. CONCLUSIONS: Evaluation of the preadoptive medical
      report is not sufficient to value the physical and mental health of the Russian
      children. In order to diminish the risk it is necessary to form to the future
      parents concerning the medical data of interest that they must obtain and the
      video characteristics that they must make, to be able to value with greater
      guarantee the physical, neurosensorial and maturative development of the assigned
      child.

PMID- 14669140
TI  - [Selective attention disorders associated with a history of occupational exposure
      to organic solvents].
AB  - INTRODUCTION: The cognitive effects of long-term exposure to organic solvents
      could be similar to those triggered by certain neurodegenerative diseases. AIMS:
      The purpose of this study was to evaluate the effects exerted by accumulated
      exposure on the cognitive functions. PATIENTS AND METHODS: 105 subjects with an
      average history of exposure of 19.3 years were evaluated using seven computerised
      cognitive tasks (CPT, digit-symbol substitution, Stroop, memory span, word
      learning and recognition, and TRD) and results were later compared with the
      performance of a non-exposure group and with a normative reference. A study was
      made of the association between the length of exposure and performance in the
      variables in which the exposed subjects displayed significantly lower values than
      control subjects. In order to evaluate the effect exerted by age, regression
      functions between performance and age were calculated for each group. RESULTS:
      Only the indicators from the Stroop and digit-symbol tasks correlated with the
      length of exposure. The regression functions between performance and age for each
      group showed that the former decreased significantly faster among exposed
      subjects than among controls. CONCLUSIONS: Findings suggest that, while recent
      exposure seems to have an effect on a wide range of functions, chronic exposure
      exerts a selective influence on a smaller group. In this case, only selective
      attention appears to deteriorate. Similar deficits have been observed in the
      early stages of patients with Alzheimer's and Parkinson's.

PMID- 14669141
TI  - [Use of anticonvulsive drugs during pregnancy and the risk of malformations in
      the newborn: a meta-analysis].
AB  - OBJECTIVE: To determine the risk, if any, of anticonvulsants use on the foetus
      with respect to major malformations. MATERIALS AND METHODS: MEDLINE, EMBASE,
      SCISEARCH and programs as ProQuest, HINARI and Ovid were searched for human
      studies. Studies that examined the effects of systematic exposure to any
      anticonvulsant during pregnancy (any dose, any duration, indicated for any type
      of epilepsy) were eligible. Studies that assessed major malformations in the
      infants were eligible. Major malformations were defined using the criteria
      described by Holmes. The number of neonates exposed to anticonvulsants who did
      and did not exhibit major malformations, and the number of neonates not exposed
      to anticonvulsants who did and did not exhibit major malformations, were
      extracted in the form of 2 x 2 tables. The odds ratio (OR), relative risk and 95%
      confidence interval (CI) was calculated for each of the studies. RESULTS: Ten
      cohort studies and four case control studies were included. A total of 2,509
      cases and 433,890 controls were included. Major malformations were found in 9.8%
      among the exposed children and 7.4% among the non exposed. (OR: 2.7; CI 95%:
      2.062-3.641; p<0.000). There was no evidence of an association between any
      anticonvulsant and a specific major malformation. CONCLUSIONS: The available
      epidemiological data support the hypothesis that anticonvulsants increase the
      risk of major malformations by an order of 2- to 3-fold.

PMID- 14669142
TI  - [A single deletion of mitochondrial DNA in a Brazilian patient with chronic
      progressive external ophthalmoplegia].
AB  - INTRODUCTION: The syndrome of chronic progressive external ophthalmoplegia (CPEO)
      has been associated to the presence of large deletion, single or multiple, in the
      mitochondrial DNA of skeletal muscle. CASE REPORT: We report a sporadic case of
      chronic progressive external ophthalmoplegia that began at age 19 years and was
      associated with ragged red fibers in skeletal muscle. Genetic analysis of
      mitochondrial DNA revealed the presence of a single deletion of 4237 bp that
      encompasses the nucleotide positions 9486 to 13722, a location that has not been
      described before, and flanked by a direct repeat sequence. The deletion is
      flanked by a direct repeat. CONCLUSIONS: The amount of deleted mitochondrial DNA
      (55%) in this patient's muscle suggests that this deletion is the molecular cause
      of the phenotypic presentation of this patient.

PMID- 14669143
TI  - [Ischemic optic neuropathy following a dural arteriovenous fistula. Vascular
      steal phenomenon].
AB  - CASE REPORT: We report the case of a 46-year-old patient, with a dural
      arteriovenous fistula in the left cavernous sinus fed by dural branches of both
      carotid siphons, by recurrent branches of the left ophthalmic artery (LOA) and by
      dural branches of the left external carotid artery. Twenty-four hours after
      arterial embolisation with polyvinyl alcohol particles, the patient suffered
      visual loss in the left eye. All feeders were embolized except the recurrent
      branches of the LOA, which became hypertrophied. Fluorescein angiography of the
      retina was normal. Transocular Doppler ultrasound showed a turbulent, inverted,
      low resistance flow in the LOA distal part, and a high resistance anterograde
      flow in the left central artery of the retina, which accounted for an ischemic
      optic neuropathy. CONCLUSIONS: The ischemic optic neuropathy resulted from a
      vascular steal phenomenon. Hypertrophy of recurrent branches of the LOA, after
      embolization of the remaining feeders, contributed to a low resistance shunt
      between the LOA proximal part and the left cavernous sinus. This shunt caused the
      inversion of flow in the distal part of the artery and the subsequent decrease of
      retrobulbar blood supply.

PMID- 14669144
TI  - [Recurring ischemic cerebral infarction caused by primary thrombocytosis in
      infancy].
AB  - INTRODUCTION: Ischemic cerebrovascular disease includes a set of entities that
      are produced by disorders in components of the blood, the blood flow, the walls
      of blood vessels or the heart, and can be anatomical, functional or even mixed.
      CASE REPORT: We describe the case of an 18-month-old male patient with
      compensated celiac disease, with repeated ischemic strokes in different
      territories, including the right posterior cerebral artery and middle cerebral
      artery, in the course of a hypercoagulable state due to essential thrombocytosis.
      Computerised axial tomography scans, brain angioresonance, a complete blood
      chemistry analysis and bone marrow biopsy were all performed and confirmed the
      previous diagnosis. Exchange transfusion, antiplatelet drugs and a platelet
      production inhibitor (anagrelide) were begun as therapy. At present, the patient
      is 2 years old and still has a slight direct hemiparesis, which is complete and
      predominantly faciobrachial, with no alterations to language. CONCLUSIONS:
      Cerebral infarctions in infancy are infrequent, and their presentation obliges
      the attending clinician to seek causes that are not usual. In our patient the
      hypocoagulability came about due to essential thrombosis, which is rare in
      infancy. The cause behind the infarction determines the chances of its recurring.
      Acetylsalicylic acid did not prove to be effective for this purpose. We suggest
      using carbamazepine for the treatment of kinesigenic dystonias.

PMID- 14669145
TI  - [Hyperhomocysteinemia-related cerebral venous thrombosis].
AB  - INTRODUCTION: Moderate hyperhomocysteinemia is a causal risk factor for
      atherosclerosis and venous thromboembolism. Recent researches have tried to find
      out a causal relationship. However, only a small number of cases have been
      reported on hyperhomocysteinemia and cerebral venous thrombosis in the world
      medical literature. CASE REPORT: We present the case of a 21 years old woman, and
      oral contraceptives taker, who consulted for a one week clinical picture of
      biparietal headache, nausea and vomiting. Examination revealed bilateral
      papilledema, and subsequent CT scan, MRI and MR angiography showed thrombosis of
      the left lateral sinus. Immunologic tests (antinuclear antibodies,
      antiphospholipid antibodies) were negative. Hypercoagulability studies showed
      persistent homocysteine high levels. The patient improved and was discharged
      after treatment with anticoagulants and therapeutic measures against brain edema.
      DISCUSSION: The 70 percent of the patients with thrombosis of the cerebral venous
      sinuses present hypercoagulable states, including moderate hyperhomocysteinemia.
      Several mechanisms are proposed for venous thrombosis in hyperhomocysteinemia,
      homocysteine induced endothelial dysfunction between others. Otherwise, oral
      contraceptives can increase the risk of venous thrombosis in other prothrombotic
      conditions. Folic acid and vitamins supplementation therapy are commented.

PMID- 14669146
TI  - [Brain aneurysms: an infrequent cause of transient ischemic stroke].
AB  - INTRODUCTION: Ischemic symptomatology related to the presence of saccular brain
      aneurysms is infrequent, and this makes it difficult to reach a widespread
      agreement about the most suitable treatment. CASE REPORT: A 17-year-old male with
      symptoms of little stroke produced by distal embolisation of an aneurysm in the
      middle cerebral artery. The patient was treated by endovascular aneurysm
      exclusion. CONCLUSIONS: In patients with no other identifiable cause of ischemic
      attacks, the possible presence of a brain aneurysm must be taken into account.
      First choice treatment is the obliteration of the aneurysm using endovascular
      techniques. If the approach to the aneurysm (either endovascular or surgical)
      entails a high risk for the patient, another possibility is to use antiplatelet
      drugs.

PMID- 14669148
TI  - [The various meanings of the term 'omnipotence'].
AB  - DEVELOPMENT: In this paper, we briefly review the characteristics of the how the
      human psychobiological unit progresses in the early ages. The pre-eminence of the
      affective axis is underlined, the shades of narcissism, egocentrism and pseudo
      omnipotence present in such early stages are highlighted, and emphasis is placed
      on how the morbid persistence of such shades throughout adult life can distort
      the subject's evaluations. This is more specifically so if they badly taint the
      subject's image of God. The author briefly analyzes the organic stratum
      underlying emotional affective life and discusses the relationships of the joint
      integration between the brain and the visceral world. The study also includes
      contributions by leading Spanish thinkers about the serene conception of the
      omnipotence of God and finishes by comparing the complexity of the brain with the
      interaction of the galaxies in the universe. CONCLUSIONS: The paper describes the
      psychobiological structure of the human personality, from its most archaic and
      childish positions, steeped in egocentrism and pseudo-omnipotence, and points out
      how they extend into adulthood. The frequency and the risk of projections of God
      (not abstract, not 'all-embracing') are also stressed, and the most up to date
      and serene theology is followed. It is pointed out that the complexity of the
      brain is greater than that of a system of galaxies.

PMID- 14669149
TI  - Hepatic induction of mitochondrial and cytosolic acyl-coenzyme a
      hydrolases/thioesterases in rats under conditions of diabetes and fasting.
AB  - Acyl-coenzyme A (CoA) hydrolases/thioesterases are a group of enzymes that
      catalyze the hydrolysis of acyl-CoA thioesters to free fatty acids and CoA-SH.
      The potency of these enzymes may serve to modulate intracellular concentrations
      of acyl-CoAs, free fatty acids, and CoA to affect various cellular functions,
      including lipid metabolism. In this study, we investigated the effect of diabetes
      and fasting on the protein levels of mitochondrial (MTE-I) and cytosolic acyl-CoA
      thioesterases (CTE-I), multigene family members of this class of enzymes, in
      adult rat liver. Rats were treated with alloxan to induce diabetes or fasted for
      72 hours. Western blot analysis with the liver homogenates revealed 2.8-fold and
      3.8-fold increases in MTE-I and 8.5-fold and 9.2-fold increases in CTE-I under
      the diabetic and fasting conditions, respectively, compared with the control in
      which the level of MTE-I was 4.3-fold higher than CTE-I. Serum level of free
      fatty acids was elevated 5-fold and 2.5-fold in diabetic and fasted rats,
      respectively. These results confirm the adaptive induction of MTE-I and CTE-I in
      response to fatty acid overload in the liver, being consistent with their
      auxiliary role in fatty acid degradation.

PMID- 14669150
TI  - Apolipoprotein AI- and AI:AII-containing lipoproteins in white men and women of
      the HERITAGE Family study: Associations with metabolic risk profile variables.
AB  - It is now well established that an increased high-density lipoprotein (HDL)
      cholesterol level, especially in the HDL(2) subfraction, is associated with a
      reduced risk of coronary heart disease (CHD). However, little is known about the
      associations between the apolipoprotein (apo) composition of HDL and CHD
      metabolic risk factors. In the present study, we examined the gender differences
      in plasma concentration of HDL containing apo AI only (LpAI) versus both apoAI
      and apoAII (LpAI/AII), and also compared their associations with body
      composition, adipose tissue (AT) distribution, and metabolic risk profile
      variables. For that purpose, we measured fasting plasma lipoprotein-lipid levels
      including LpAI and LpAI/AII concentrations in a sample of 215 men and 174 women,
      all Caucasians, of the HERITAGE Family Study. All subjects underwent
      anthropometric, body fatness (underwater weighing) and abdominal AT accumulation
      (computed tomography) measurements. We found that, women had higher LpAI and
      lower LpAI/AII concentrations compared with men. Whereas in women, LpAI levels
      were correlated to body fat mass and waist circumference, no association between
      body composition, fat distribution, and LpAI concentrations was noted in men.
      Increased LpAI concentrations were associated with higher HDL(2) cholesterol
      levels in both men and women. Overall, elevated LpAI and LpAI/AII concentrations
      showed contrasting associations with metabolic risk profile variables as high
      LpAI, but not LpAI/AII concentrations were associated with a more favorable
      metabolic risk profile. We also found that high HDL cholesterol appeared to be
      more closely related to a better metabolic risk profile than high LpAI in both
      genders. Our results suggest that LpAI and HDL cholesterol levels are good
      correlates of the metabolic profile, but that HDL cholesterol concentrations
      could still represent a better index in CHD risk assessment.

PMID- 14669151
TI  - Postprandial changes in the distribution of apolipoprotein AIV between
      apolipoprotein B- and non apolipoprotein B-containing lipoproteins in obese
      women.
AB  - Plasma apolipoprotein AIV (apo AIV) level has been shown to be a good marker of
      triglyceride changes after a high-fat diet. However, the distribution of apo AIV
      between apo B- and non-apo B-containing lipoproteins (Lp) during the postprandial
      state has not been described as well as the influence of obesity on this
      distribution. Our aim was to study the influence of parameters related to obesity
      and insulin resistance on the postprandial changes in apo AIV-containing Lp after
      a high-fat meal in obese women. Twenty-three overweight or obese women (body mass
      index [BMI] ranging from 29.1 and 64.0 kg.1 m(-2)), for whom blood samples were
      taken after fasting overnight, participated in the study. Thirteen of these obese
      women were given a fatty meal and, in this case, blood samples were taken at fast
      and 30 minutes, 1, 2, 4, and 6 hours after ingestion of the fat meal. Apo AIV
      containing particle families, Lp B:AIVf (family [f] of particles containing at
      least apo B and apo AIV) and Lp AIV non-Bf (family [f] of particles containing
      apo AIV, but free of apo B) were quantified by sandwich enzyme-linked
      immunosorbent assay (ELISA). When fasting, Lp B:AIVf and Lp AIV non-Bf did not
      correlate with any of the parameters related to obesity and insulin resistance,
      if one excepts a positive correlation between HDL-cholesterol (HDL-C) and Lp AIV
      non-Bf. Postprandial lipemia was associated with a trend towards an increase in
      the plasma levels of apo AIV-containing Lp 6 hours after fat ingestion. The
      postprandial peak of Lp B:AIVf and Lp AIV non-Bf occurred 2 hours after the
      triglyceride peak. The distribution between apo B- and non-apo B-containing Lp
      did not change after ingestion of the fat meal, if one excepts a tendancy towards
      a lower ratio of bound and nonbound forms at 8 hours. Fasting plasma Lp B:AIVf
      concentration correlated with the area under the curve (AUC) of plasma
      triglycerides (beta = 0.11, P <.02). In a multivariate analysis, BMI (beta =
      51.85, P <.001), fasting triglycerides (beta = 431.08, P <.01), and low-density
      lipoprotein-cholesterol (LDL-C) (beta = 2638.57, P <.005) were independent and
      positive determinants of the AUC of Lp AIV non-Bf, while waist circumference
      (beta = -23.94, P <.001), cholesterol (beta = -1655.02, P <.01), and systolic
      blood pressure (beta = -6.34, P <.05) were negative and independent determinants
      of this AUC. Fasting Lp B:AIVf may represent a good marker of the postprandial
      triglyceride increase in obese women. Changes in apo AIV concentrations in apo B-
      and non-apo B-containing Lp after a fat meal depend mainly on the degree of
      obesity rather than on insulin resistance. This effect is more obvious for Lp AIV
      non-Bf than for Lp B:AIVf.

PMID- 14669152
TI  - The relationship between simple anthropometric indices and C-reactive protein:
      ethnic and gender differences.
AB  - C-reactive protein (CRP) is an independent risk factor for cardiovascular disease
      (CVD) that is strongly associated with indicators of body fat, yet the effect of
      potential confounders, such as ethnic background and gender has not been
      characterized. Our purpose was to determine the effect ethnicity and gender has
      on the relationship between CRP, body mass index (BMI), waist circumference (WC),
      and waist-to-hip ratio (WHR) in men and women of Chinese and European descent.
      BMI, WC, WHR, and CRP were measured in European (n = 91) and Chinese (n = 91) men
      and women recruited from local hospital staff. Pearson correlation coefficients
      were determined between CRP, age, and anthropometric measures for the entire
      cohort and stratified by ethnicity and gender. Multiple regression analyses were
      performed using interactions between BMI, WC, and WHR for each ethnicity and
      gender with CRP as the outcome. CRP levels were significantly lower in Chinese
      compared with Europeans, but this difference disappeared after correction for
      either BMI or WC. In women, BMI (r =.55, P <.01) and WC (r =.59, P <.01)
      correlated with CRP. Gender significantly interacted with WC to predict CRP after
      adjusting for age, smoking status, alcohol, and BMI (P <.05). There was a
      nonsignificant interaction between gender and BMI as a predictor of CRP.
      Differences in CRP remained significant after adjusting for WHR. The relationship
      between CRP levels and BMI or WC was similar between men and women of Chinese and
      European descent. Gender significantly modified the relationship between CRP and
      WC. At a WC beyond 70 cm, CRP levels increased at a greater rate in women than
      men.

PMID- 14669153
TI  - Lipoprotein lipase activator NO-1886 (ibrolipim) accelerates the mRNA expression
      of fatty acid oxidation-related enzymes in rat liver.
AB  - The lipoprotein lipase (LPL) activator NO-1886 (ibrolipim) has been shown to have
      potential benefits for the treatment of obesity in rats. However, the anti
      obesity mechanism of NO-1886 has not been clearly understood. To address this, we
      studied the effects of NO-1886 on the mRNA expression of fatty acid oxidation
      related enzymes in rats. The respiratory quotient (RQ) in rats administered a
      single oral dose of NO-1886 was significantly lower than control rats under both
      fed and fasted conditions. NO-1886 orally administered to rats for 7 days caused
      1.54-fold increase in carnitine palmitoyl transferase II (CPTII) mRNA in the
      carnitine palmitoyl transferase system. Furthermore, NO-1886 caused a 1.47-fold
      increase in long-chain acyl-CoA dehydrogenase (LCAD) mRNA, a 1.49-fold increase
      in acetyl-CoA acyltransferase 2 (ACAA2) mRNA, and a 1.24-fold increase in enoyl
      CoA hydratase (ECH) mRNA in rats, all which are liver beta-oxidation enzymes. NO
      1886 also increased uncoupling protein-2 (UCP2) mRNA levels in liver by 1.42-fold
      when compared to the control group. These results suggest that the LPL activator
      NO-1886 may accelerate the expression of fatty acid oxidation-related enzymes,
      resulting in a reduction of RQ.

PMID- 14669154
TI  - Metabolic and psychosocial effects of minimal invasive gastric banding for morbid
      obesity.
AB  - Obesity is considered a primary risk factor for cardiovascular disease and
      related mortality. The current study aimed to investigate the efficacy of minimal
      invasive gastric banding (GB) surgery for reducing caloric intake in morbid
      obesity, and to analyze the effects of weight loss on body composition and
      metabolic and psychosocial outcomes. Twenty-six adult severely obese patients
      (mean body mass index [BMI], 48.1 kg/m(2); range, 42 to 56) underwent adjustable
      silicone laparoscopic GB. Nine additional obese patients who declined surgery
      were treated with metformin (2 g daily) and served as a small additional group
      (BMI, 50.5 kg/m(2); range, 41 to 68). Presurgery and 17 +/- 2.2 months
      postoperatively, body composition (fat mass [FM], lean body mass [LBM], body
      water) and serum parameters (lipids, glucose, thyrotropin-stimulating hormone
      [TSH]) were determined. Quality of life (QoL) was evaluated by a standardized
      self-rating questionnaire (Short Form-36 [SF-36]), and supplemented by measures
      of physical complaints and psychological distress. After GB, weight loss was 21
      +/- 14.9 kg (14%, P <.001). It was associated with a decrease in FM by 14 +/- 8.6
      kg (18%, P <.001), LBM by 4 +/- 2.7 kg (5%, P <.001), body water by 4 +/- 3.4 L
      (7%, P <.01), systolic blood pressure by 16 +/- 26.3 mm Hg (10%, P <.05), total
      cholesterol by 0.69 +/- 1.29 mmol/L (12%, P <.05), and low-density lipoprotein
      cholesterol (LDL-C) by 0.38 +/- 0.39 mmol/L (10%, P <.05). Highly significant
      interactions between surgery and time were noted for weight (P <.005), BMI (P
      <.005), and FM (P <.007, analysis of variance [ANOVA]). Preoperatively, 14 of 26
      patients (54%) had high fasting blood sugar levels (type 2 diabetics) and 11
      (42%) had impaired glucose tolerance, whereas postoperatively, for baseline
      glucose levels a trend to decrease was noted. Neither malabsorption nor anemia
      was observed. QoL improved after GB; in particular, physical functioning and well
      being increased (P <.01), and somatic complaints (eg, dyspnea and heart
      complaints, pain in legs and arms) markedly decreased (P =.008). In the metformin
      group, neither relevant weight loss nor a significant decrease of biochemical
      values was observed. Minimal invasive GB is a successful therapeutic tool for
      reducing FM in morbidly obese patients. Weight loss resulted in improved
      metabolic parameters, suggesting a lowered atherogenic risk.

PMID- 14669155
TI  - Mechanisms involved in the stimulatory effect of advanced glycation end products
      on growth of rat aortic smooth muscle cells.
AB  - Hyperglycemia is an important cause of accelerated atherosclerosis in diabetic
      patients. We examined the effect of hyperglycemia and advanced glycation end
      products (AGE) on proliferation of rat aortic smooth muscle cells (SMC) in
      culture; in vivo, this event is believed to contribute importantly to
      atherogenesis in diabetes mellitus. Glucose itself dose-dependently inhibited
      thymidine uptake by SMC, but AGE increased thymidine uptake, suggesting that SMC
      proliferation is accelerated by AGE. To examine possible mechanisms for this
      effect, we studied nuclear factor-kappa B (NF-kappaB) activation and the tyrosine
      phosphorylation pathway; AGE stimulated NF-kappaB activity, but phosphorylation
      of the platelet-derived growth factor (PDGF) receptor was unchanged. In Chinese
      hamster ovary (CHO) cells overexpressing galectin-3, an AGE receptor related to
      atherosclerosis, AGE increased thymidine uptake. This suggests SMC proliferation
      is enhanced by AGE via galectin-3. As pathways involving AGE-galectin-3
      interaction thus may be involved in macroangiopathy, AGE appears to be important
      to the role of SMC in accelerated atherosclerosis associated with diabetes
      mellitus.

PMID- 14669156
TI  - Association of cholesteryl ester transfer protein activity and TaqIB polymorphism
      with lipoprotein variations in Japanese subjects.
AB  - Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl
      ester from high-density lipoprotein (HDL) to apolipoprotein (apo)B-containing
      lipoproteins, whereby it potentially regulates steady-state concentrations of HDL
      cholesterol (HDL-C), as well as low-density lipoprotein-cholesterol (LDL-C). We
      performed a multicenter trial to assess the association of CETP activity with
      plasma lipoprotein levels in 591 Japanese subjects. Women had significantly
      higher CETP activity (15%) and mass (24%) compared to men. For both genders CETP
      activity was negatively correlated with HDL-C and HDL(2)-C, but positively
      correlated with LDL-C. B2 allele frequency in TaqIB polymorphism was 40%, with no
      gender difference. TaqIB genotypes were significantly associated with CETP
      activity and HDL-C level (both P <.001). B1B1 had the highest CETP activity and
      the lowest HDL-C concentrations, whereas B2B2 had the lowest CETP activity and
      the highest HDL-C concentrations. However, no statistically significant
      differences in triglycerides (TG) or LDL-C were observed across TaqIB genotypes.
      Multivariate analysis revealed that determinants of HDL-C were age, gender, body
      mass index (BMI), smoking, alcohol intake, exercise, CETP activity, and TG, and
      for LDL-C were BMI, age, and CETP. These data demonstrate that CETP activity is a
      significant determinant of HDL-C and LDL-C levels and that TaqIB CETP gene
      polymorphism affects CETP activity and HDL-C level in Japanese population
      examined.

PMID- 14669157
TI  - Substrate concentration and metabolism in left and right muscles of rats.
AB  - Skeletal muscle fiber heterogeneity among muscle groups is well known; however,
      laterality of muscle metabolism has not been addressed. In the present studies,
      metabolite concentrations in left and right gastrocnemius, tibialis anterior,
      quadriceps, and soleus muscles and their response to exogenous insulin have been
      compared in fasted awake rats. The results indicated that the concentrations of
      muscle free glycerol (P >.4), glycerol 3-phosphate (P >.1) nonesterified fatty
      acids (NEFA) (P >.6) and intramyocellular triglycerides (imcTG) (P >.08) are
      comparable between left and right of the same muscle, and are similar among mixed
      glycolytic-oxidative muscles. The concentration of free glycerol in soleus
      responded to exogenous insulin in a pattern distinct to that seen for the mixed
      muscles. The results support interchangeable use of left and right side of same
      muscles, and probably among different muscles of similar fiber type, but not
      muscles of different fiber types.

PMID- 14669158
TI  - Effect of improving glycemic control on low-density lipoprotein particle size in
      type 2 diabetes.
AB  - The current study sought to assess the effect of improving glycemic control in
      type 2 diabetes on the components of diabetic dyslipidemia, especially low
      density lipoprotein (LDL) size. A total of 33 type 2 diabetic patients (48.5%
      women, age 59.6 +/- 11.1 years, body mass index [BMI] 28.9 +/- 4.9, diabetes
      duration 6 [0 to 40] years, 40.7% on insulin) were seen at the hospital because
      of poor glycemic control (hemoglobin A(1c) [HbA(1c)] 10.33% +/- 1.89%).
      Triglyceride, LDL-cholesterol (LDLc, Friedewald/ ultracentrifugation), high
      density lipoprotein HDL-cholesterol (HDLc, direct method), apolipoproteins AI
      (apoAI) and B (apoB) (immunoturbidimetry), and LDL size (gradient gel
      electrophoresis) were measured at baseline and after improvement in glycemic
      control (decrease >/= 1 percentage point in HbA(1c) and final HbA(1c) </= 8%).
      Improvement in glycemic control (HbA(1c) 7.01% +/- 0.63%, P <.0005 v baseline)
      after a follow-up of 3.5 (range, 1 to 13) months resulted in a significant
      reduction in LDLc (3.34 +/- 1.02 v 3.62 +/- 1.15 mmol/L, P <.05) and apoB (1.07
      +/- 0.25 v 1.17 +/- 0.29 g/L, P <.01) and an increase in HDLc (1.21 +/- 0.32 v
      1.13 +/- 0.34 mmol/L, P <.05) and apoAI (1.36 +/- 0.24 v 1.27 +/- 0.24 mmol/L, P
      < 0.01) in the whole group, and an increase in LDL particle size (25.61 +/- 0.53
      v 25.10 +/- 0.31 nm, P <.005) in the 14 patients showing LDL phenotype B at
      baseline. No significant changes were seen in body weight or BMI. We conclude
      that improvement of glycemic control in type 2 diabetes improves most of the
      components of diabetic dyslipidemia, including a shift towards larger LDL
      particles in subjects with phenotype B.

PMID- 14669159
TI  - Similar insulin secretory response to a gastric inhibitory polypeptide bolus
      injection at euglycemia in first-degree relatives of patients with type 2
      diabetes and control subjects.
AB  - Insulin secretion following the intravenous infusion of gastric inhibitory
      polypeptide (GIP) is diminished in patients with type 2 diabetes and at least a
      subgroup of their first-degree relatives at hyperglycemic clamp conditions.
      Therefore, we studied the effects of an intravenous bolus administration of GIP
      at normoglycemic conditions in the fasting state. Ten healthy control subjects
      were studied with an intravenous bolus administration of placebo, and of 7, 20,
      and 60 pmol GIP/kg body weight (BW), respectively. Forty-five first-degree
      relatives of patients with type 2 diabetes and 33 matched control subjects were
      studied with (1) a 75-g oral glucose tolerance test (OGTT) and (2) an intravenous
      bolus injection of 20 pmol GIP/kg BW with blood samples drawn over 30 minutes for
      determination of plasma glucose, insulin, C-peptide, and GIP. Statistical
      analysis applied repeated-measures analysis of variance (ANOVA) and Duncan's post
      hoc tests. Insulin secretion was stimulated after the administration of 20 and of
      60 pmol GIP/kg BW in the dose-response experiments (P <.0001). GIP administration
      (20 pmol/kg BW) led to a significant rise of insulin and C-peptide concentrations
      in the first-degree relatives and control subjects (P <.0001), but there was
      difference between groups (P =.64 and P =.87, respectively). Also expressed as
      increments over baseline, no differences were apparent (Delta(insulin), 7.6 +/-
      1.2 and 7.6 +/- 1.6 mU/L, P =.99; Delta(C-peptide), 0.35 +/- 0.06 and 0.38 +/-
      0.08 ng/mL, P =.75). Integrated insulin and C-peptide responses after GIP
      administration significantly correlated with the respective insulin and C-peptide
      responses after glucose ingestion (insulin, r = 0.78, P <.0001; C-peptide, r =
      0.35, P =.0015). We conclude that a reduced insulinotropic effect of GIP in first
      degree relatives of patients with type 2 diabetes cannot be observed at
      euglycemia. Therefore, a reduced GIP-induced insulin secretion in patients with
      type 2 diabetes and their first-degree relatives at hyperglycemia is more likely
      due to a general defect of B-cell function than to a specific defect of the GIP
      action.

PMID- 14669160
TI  - Lipolysis in skeletal muscle is decreased in high-fat-fed rats.
AB  - The intracellular triglyceride content in skeletal muscle is increased in insulin
      resistant states such as obesity or high-fat feeding. It has been hypothesized
      that increased fatty acid oxidation resulting from increased lipolysis of
      intramyocellular triglycerides may be responsible for this insulin resistance.
      This study was undertaken to examine whether insulin resistance is associated
      with increased lipolysis in skeletal muscle in rats fed a high-fat diet. Sprague
      Dawley rats were fed a high-fat diet for 5 weeks. Lipolysis in skeletal muscle
      and adipose tissue was determined by measuring the interstitial glycerol
      concentrations using a microdialysis method in basal and hyperinsulinemic
      euglycemic clamp conditions. In the basal state, plasma free fatty acid (FFA)
      levels were higher in high-fat-fed rats than in low fat-fed rats (P <.05). In
      contrast, plasma glycerol levels (P <.001) and interstitial glycerol
      concentrations of skeletal muscle (P <.05) and adipose tissue (P <.01) were lower
      in high fat-fed rats than in low fat-fed rats. Plasma (P <.05) and interstitial
      glycerol concentrations (P <.05 for skeletal muscle, P <.01 for adipose tissue)
      during the hyperinsulinemic euglycemic clamps were also lower in the high-fat
      diet group. These results do not support the idea that increased fatty acid
      oxidation resulting from increased lipolysis of intramyocellular triglycerides is
      responsible for the insulin resistance in high fat-fed rats.

PMID- 14669161
TI  - What is the contribution of differences in three measures of tumor necrosis
      factor-alpha activity to insulin resistance in healthy volunteers?
AB  - To address the potential role that tumor necrosis factor-alpha (TNF-alpha) might
      play in modulation of insulin resistance in healthy, nondiabetic individuals, we
      compared plasma TNF-alpha and soluble TNF-alpha receptor 2 (sTNF-R2)
      concentrations, as well as TNF-alpha polymorphisms, in 94 healthy individuals,
      stratified into insulin-resistant (IR) and insulin-sensitive (IS) groups based on
      their plasma insulin concentrations 120 minutes after oral glucose on 2 occasions
      (1993 and 2000). The IR group (n = 50; 29 men and 21 women) was in the upper
      quartile and the IS group (n = 44; 24 men and 20 women) in the lowest quartile of
      the distribution of post-glucose challenge insulin concentrations in a large
      unselected population (>50 v <23 microU/mL). The IR group had significantly
      higher values for body mass index, waist-to-hip girth, fasting and post-glucose
      challenge insulin concentrations, and fasting triglyceride concentrations, and
      lower high-density lipoprotein cholesterol concentrations as compared to the IS
      group. Despite the fact that they were relatively more obese, and insulin
      resistant, plasma concentrations of TNF-alpha were similar in the IR (1.6 +/- 0.6
      pg/mL) and IS (1.7 +/- 0.6 pg/mL) groups, as were the concentrations (5.4 +/- 1.4
      v 5.8 +/- 2.0 pg/mL) of sTNF-R2. Furthermore, TNF-alpha polymorphisms (detected
      by polymerase chain reaction [PCR]) were similar in the 2 groups, with
      essentially identical allelic frequencies of the 238 (10.3% v 9.4%) and 308
      polymorphisms (17.9% v 18.7%). In conclusion, plasma TNF-alpha and sTNF-R2
      concentrations, as well as TNF-alpha gene polymorphisms, were not different in
      healthy volunteers stratified into IR and IS groups on the basis of their plasma
      insulin response to an oral glucose challenge. Given these data, it does not
      appear that differences in TNF-alpha activity contribute to the marked variations
      in insulin action that occur in healthy individuals.

PMID- 14669162
TI  - Potassium supplementation improves the natriuretic response to central volume
      expansion in primary aldosteronism.
AB  - Potassium depletion induced by dietary potassium restriction is known to cause
      sodium retention, while potassium supplementation is known to increase urinary
      sodium excretion. However, the ability of potassium deficiency to affect
      mineralocorticoid-induced sodium retention in aldosterone-producing adenoma (APA)
      subjects has not been extensively investigated, neither in baseline conditions
      nor when facilitating natriuresis through a physiological manoeuver such as
      central blood volume expansion. With the aim of testing the hypothesis that
      potassium supplementation would attenuate the mineralocorticoid-induced sodium
      retention, in 7 APA patients elevation of serum potassium was obtained by
      infusion of isosmotic potassium chloride (KCl) at a constant rate of 36 mmol/h
      for a 2-hour period for 5 consecutive days. The same patients were also submitted
      to acute central volume expansion by head-out water immersion (WI) associated
      with either low or normal serum potassium levels. The assessment of natriuresis
      in baseline condition and during WI was also performed in 10 age-matched control
      subjects. Central hypervolemia by WI induced a significant natriuretic response
      in APA hypokalemic subjects; on the other hand, in the same APA subjects giving
      potassium supplementation, WI-induced urinary sodium excretion was significantly
      higher (P <.001) than that obtained during WI at normal potassium intake
      (hypokalemic condition). Blood pressure responses and hormonal profiles were
      almost superimposable during the 2 WI experiments performed at different serum
      potassium levels. By confirming that amelioration of hypokalemia attenuates
      mineralocorticoid-induced sodium retention, this study also suggests that
      potassium intake may represent an important determinant of mineralocorticoid
      escape.

PMID- 14669163
TI  - High levels of urinary pentosidine, an advanced glycation end product, in
      children with acute exacerbation of atopic dermatitis: relationship with
      oxidative stress.
AB  - Pentosidine is an advanced glycation end product formed by sequential glycation
      and oxidation. The formation of pentosidine is increased in diseases associated
      with oxidative stress, such as inflammatory conditions. The aim of the present
      study was to determine the urinary concentration of pentosidine in atopic
      dermatitis (AD) and its relationship to the inflammatory status of AD. Urine
      samples of 32 children with AD and 30 age-matched healthy control subjects were
      assayed for pentosidine, pyrraline (another advanced glycation end product formed
      by nonoxidative glycation), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) (an
      established marker of oxidative stress). Of these 3 markers, urinary
      concentrations of pentosidine were significantly higher in patients with acute
      exacerbation of AD than in healthy controls and patients with stable AD. Urinary
      concentrations of 8-OHdG were significantly higher in AD patients with and
      without acute exacerbation than in healthy controls. Urinary pentosidine levels
      correlated significantly with those of 8-OHdG when all data of healthy controls
      and AD patients were plotted. In patients with acute exacerbation of AD, both
      urinary pentosidine and 8-OHdG significantly decreased after 7 to 9 days of
      treatment. Our findings in patients with acute exacerbation of AD suggest that
      pentosidine levels are partly determined by the prevailing oxidative stress in
      these patients.

PMID- 14669164
TI  - Enhanced insulin signaling via Shc in human breast cancer.
AB  - Insulin is a mild mitogen and has been shown to potentiate mitogenic influence of
      other growth factors. Because hyperinsulinemia and/or overexpression of insulin
      receptors have been linked to development, progression, and outcome of breast
      cancer, we attempted to evaluate the mechanism of these associations. We have
      compared the expression of insulin receptors and the magnitude of insulin
      signaling in breast tumors and adjacent normal mammary tissue samples obtained
      from 20 patients. We observed that insulin binding more than doubled in the
      tumors as compared with the normal tissue (P <.01 by paired t test). Insulin
      signaling to Shc, judged by the magnitude of its phosphorylation, was also
      significantly enhanced in the tumors. In contrast, the phosphorylation of the
      insulin-receptor substrate-1 (IRS-1), Akt, and mitogen-activated protein (MAP)
      kinase were identical in the tumorous and normal mammary tissues. Finally, tumors
      displayed significantly increased amounts of farnesylated p21 Ras and
      geranylgeranylated Rho-A (P <.01), consistent with Shc-dependent activation of
      farnesyl (FTase) and geranylgeranyl transferases (GGTase) in the tumor tissue. We
      conclude that the mechanism of the mitogenic influence of insulin in breast
      cancer may include increased expression of insulin receptors, preferential
      hyperphosphorylation of Shc, and increased amounts of prenylated p21 Ras and Rho
      A in tumor tissue as compared with adjacent normal mammary tissue.

PMID- 14669165
TI  - Low adipocyte-derived plasma protein adiponectin concentrations are associated
      with the metabolic syndrome and small dense low-density lipoprotein particles:
      atherosclerosis and insulin resistance study.
AB  - Circulating plasma adiponectin, an adipocyte-derived protein, has been shown to
      be decreased in obese subjects as well as in patients with type 2 diabetes and
      also in subjects who do not have diabetes, but are insulin resistant. We assessed
      the relationship between plasma levels of adiponectin, the metabolic syndrome and
      the occurrence of small dense LDL particles (pattern B) in 101 clinically healthy
      middle-aged subjects recruited from the general population. Low adiponectin
      levels were associated with the metabolic syndrome and low-density lipoprotein
      (LDL) particle size (r =.55, P <.001). The relationship between adiponectin and
      LDL particle size remained in a multiple regression model, in which adiponectin
      and total body fat explained 30% of the variability in LDL particle size.
      Furthermore, subjects in the lowest tertile of adiponectin had an increased risk
      of having pattern B (risk odds ratio [ROR] = 5.6). Because this was a cross
      sectional study, no conclusions can be drawn about causality. This is the first
      population-based study in man demonstrating a relationship between small dense
      LDL particles and adiponectin.

PMID- 14669166
TI  - Regulation of glucose kinetics during intense exercise in humans: effects of
      alpha- and beta-adrenergic blockade.
AB  - This study examined the effect of combined alpha- and beta-adrenergic blockade on
      glucose kinetics during intense exercise. Six endurance-trained men exercised for
      20 minutes at approximately 78% of their peak oxygen consumption (Vo(2))
      following ingestion of a placebo (CON) or combined alpha- (prazosin
      hydrochloride) and beta- (timolol maleate) adrenoceptor antagonists (BLK). Plasma
      glucose increased during exercise in CON (0 minutes: 5.5 +/- 0.1; 20 minutes: 6.5
      +/- 0.3 mmol. L(-1), P <.05). In BLK, the exercise-induced increase in plasma
      glucose was abolished (0 minutes: 5.7 +/- 0.3; 20 minutes: 5.7 +/- 0.1 mmol. L(
      1)). Glucose kinetics were measured using a primed, continuous infusion of [6,6
      (2)H] glucose. Glucose production was not different between trials; on average
      these values were 25.3 +/- 3.9 and 30.9 +/- 4.4 micromol. kg(-1). min(-1) in CON
      and BLK, respectively. Glucose uptake during exercise was greater (P <.05) in BLK
      (30.6 +/- 4.6 micromol. kg(-1). min(-1)) compared with CON (18.4 +/- 2.5
      micromol. kg(-1). min(-1)). In BLK, plasma insulin and catecholamines were higher
      (P <.05), while plasma glucagon was unchanged from CON. Free fatty acids (FFA)
      and glycerol were lower (P <.05) in BLK. These findings demonstrate that
      adrenergic blockade during intense exercise results in a blunted plasma glucose
      response that is due to enhanced glucose uptake, with no significant change in
      glucose production.

PMID- 14669167
TI  - Developmental plasticity in sympathetic nervous system response to fasting in
      adipose tissues of male rats.
AB  - While fasting suppresses sympathetic nervous system (SNS) activity in most
      peripheral tissues, the response of sympathetic nerves in white adipose tissue
      (WAT) is reportedly stimulatory. To confirm this finding and to determine if the
      fasting response in WAT is susceptible to developmental modification, SNS
      activity was compared in fed and fasted animals using techniques of
      [3H]norepinephrine ([3H]NE) turnover. Studies were performed in commercially
      reared 7-week-old male rats, in male rats reared in the local vivarium, and in
      male rats reared until 30 days of age at either 18 degrees C or 30 degrees C. In
      commercially reared animals, [3H]NE turnover was elevated in epididymal fat
      during the second day of fasting, a response not seen during the preceding or
      succeeding day of fasting. On the other hand, in rats reared from birth in the
      local vivarium a 1-day fast led to suppression of SNS activity in epididymal fat.
      In rats reared at 18 degrees C for the first 30 days of life, fasting suppressed
      SNS activity in retroperitoneal fat in contrast to the absence of this response
      noted in 30 degrees C-reared rats. These studies demonstrate that sympathetic
      responses in WAT to fasting in young adult, male rats are susceptible to
      modification by the environmental conditions present during the first month of
      life.

PMID- 14669168
TI  - Polycystic ovary syndrome, the G1691A factor V Leiden mutation, and plasminogen
      activator inhibitor activity: associations with recurrent pregnancy loss.
AB  - Our specific aim was to assess associations of thrombophilia, hypofibrinolysis,
      and polycystic ovary syndrome (PCOS) with recurrent pregnancy loss (RPL) (>/=3
      consecutive pregnancy losses < 20 weeks gestation). Prospective studies were
      performed in 33 Caucasian women referred for diagnosis and treatment of PCOS who
      were subsequently found to have RPL and in 16 Caucasian women referred for
      diagnosis and treatment of RPL, who did not have PCOS. Cases (PCOS-RPL, RPL
      without PCOS) were compared with controls (116 healthy Caucasian females) for the
      G1691A Factor V Leiden, G20210A prothrombin, C677T methylenetetrahydrofolate
      reductase (MTHFR), plasminogen activator inhibitor 4G/5G, and platelet
      glycoprotein PL A1A2 gene mutations. Cases were compared with controls (44
      healthy adult Caucasian females) for serologic coagulation tests including
      homocysteine, proteins C, S, free S, antithrombin III, anticardiolipin antibodies
      IgG and IgM, dilute Russel's viper venom time, activated partial thromboplastin
      time, Factor VIII, Factor XI, lipoprotein (Lp)(a), and plasminogen activator
      inhibitor activity (PAI-Fx). The 33 Caucasian women with PCOS subsequently found
      to have RPL were 10% of a cohort of 322 Caucasian women who had >/= 1 previous
      pregnancy and had been referred for diagnosis and therapy of PCOS over a 4.3-year
      period. The Factor V Leiden G1691 mutation was present in 6 of 33 women (18%)
      with PCOS-RPL and in 3 of 16 women with RPL without PCOS (19%) versus 2 of 116
      (1.7%) female controls, Fisher's P (p(f)) =.0016, p(f) =.013. The 33 PCOS-RPL
      cases also differed from the 44 female controls for high PAI-Fx (>21.1 U/mL), 38%
      versus 8%, p(f) =. 004. The thrombophilic G1691A Factor V Leiden mutation is
      associated with RPL in women with and without PCOS; hypofibrinolysis (high PAI
      Fx) is also associated with RPL in women with PCOS.

PMID- 14669169
TI  - A novel peroxisome proliferator-activated receptor (PPAR)gamma agonist, NIP-222,
      reduces urinary albumin excretion in streptozotocin-diabetic mice independent of
      PPARgamma activation.
AB  - NIP-222 is a novel peroxisome proliferator-activated receptor (PPAR)gamma
      agonist. This study provides evidence that NIP-222 decreases urinary albumin
      excretion (UAE) in diabetic mice independent of its PPARgamma activation. We
      compared the effect of NIP-222 and another PPARgamma agonist, troglitazone, on
      UAE, plasma glucose level, blood pressure, and creatinine clearance (C(cr)) in
      streptozotocin (STZ)-induced diabetic mice. Treatment for 3 weeks with NIP-222
      (30 mg/kg) was associated with a significant decrease in UAE without any change
      in blood pressure, creatinine clearance, or plasma glucose level. In contrast,
      UAE did not decrease in mice treated with troglitazone (300 mg/kg). These results
      indicate that NIP-222 has PPARgamma independent effects on UAE in diabetic mice
      and suggest that this agent may have potential to minimize the development and
      progression of diabetic nephropathy.

PMID- 14669170
TI  - Effect of pramlintide on A1C and body weight in insulin-treated African Americans
      and Hispanics with type 2 diabetes: a pooled post hoc analysis.
AB  - An unresolved problem in the management of type 2 diabetes is that improvement of
      glycemic control with insulin, insulin secretagogues, and insulin sensitizers is
      often accompanied by undesired weight gain. This problem is of particular concern
      in ethnic groups with a high propensity for diabetes and obesity, such as African
      Americans and Hispanics. Two 1-year, randomized, double-blind, placebo-controlled
      clinical trials in insulin-treated patients with type 2 diabetes have shown that
      adjunctive therapy with pramlintide, an analog of the human beta-cell hormone
      amylin, reduces A(1C) with concomitant weight loss, rather than weight gain. To
      assess the effect of pramlintide in various ethnic groups with type 2 diabetes
      using insulin, we conducted a pooled post hoc analysis of the 2 trials, which
      included all Caucasian (n = 315), African American (n = 47), and Hispanic (n =
      48) patients (age 57 years, A(1C) 9.1%, body mass index [BMI] 33 kg/m(2), mean
      values) who completed 52 weeks of treatment with either pramlintide (120 microg
      twice daily or 150 microg 3 times a day) or placebo. Primary endpoints included
      changes from baseline to week 52 in A(1C) and body weight. Collectively,
      pramlintide-treated patients achieved significant reductions from baseline in
      both A(1C) and body weight (placebo-corrected treatment effects at week 52: -0.5%
      and -2.6 kg, respectively, both P <.0001). The simultaneous reduction in A(1C)
      and body weight at week 52 was evident across all 3 ethnic groups and appeared to
      be most pronounced in African Americans (-0.7%, -4.1 kg), followed by Caucasians
      (-0.5%, -2.4 kg) and Hispanics (-0.3%, -2.3 kg). The glycemic improvement with
      pramlintide was not associated with an increased incidence of hypoglycemia over
      the entire study period (43% pramlintide v 40% placebo). Nausea, the most common
      adverse event associated with pramlintide treatment, was mostly mild and confined
      to the first 4 weeks of therapy (25% pramlintide v 16% placebo) with comparable
      patterns in the 3 ethnic groups. Thus, pending further experience, the combined
      improvement in glycemic and weight control with pramlintide treatment appears to
      be generalizable to a broad population of mixed ethnicity.

PMID- 14669171
TI  - Adrenocortical responses to submaximal exercise in postmenopausal black and white
      women.
AB  - The purpose of this study was to determine whether racial differences exist in
      the dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and
      cortisol concentrations of black and white postmenopausal women at rest and in
      response to submaximal exercise. Twenty-three postmenopausal women (13 white and
      10 black) were studied on 2 occasions. On one occasion subjects rested quietly
      for 4 hours (control day), whereas on the other occasion after 50 minutes of
      rest, subjects exercised at 70% of Vo(2) peak for 30 minutes on a cycle ergometer
      (exercise day). Blood was sampled at rest, during exercise, and during recovery
      and assayed for DHEA, DHEAS, and cortisol concentrations. Resting DHEA and
      cortisol concentrations and integrated area under the curve (AUC) were similar
      between the black and white women; however, the black women had lower resting
      DHEAS concentrations compared with the white women (DHEAS, black: 1.32 +/- 0.29 v
      white: 2.18 +/- 0.25 micromol. L(-1), P <.05). Regardless of race, DHEA and
      cortisol AUC increased significantly above resting values (P <.01), but the
      exercise AUC for DHEA and cortisol were not different between the black and white
      women (DHEA: 607 +/- 133 and 824 +/- 108 min x nmol. L(-1); cortisol: 9,604 +/-
      1,247 and 8,076 +/- 1,093 min x nmol. L(-1), respectively). No exercise-induced
      change in integrated DHEAS AUC was found in either group. In conclusion, racial
      differences exist in the resting DHEAS levels of postmenopausal women, but with
      no racial differences in resting DHEA and cortisol concentrations. Race had no
      impact on these adrenal hormone responses to submaximal exercise.

PMID- 14669172
TI  - Pro12Ala polymorphism of the PPAR-gamma2 gene is related to increased levels of
      oxidized low-density lipoprotein (LDL) autoantibodies in patients with type 2
      diabetes mellitus.

PMID- 14669176
TI  - Healing of advanced pressure ulcers by a generic total contact seat: 2 randomized
      comparisons with low air loss bed treatments.
AB  - DESIGN: Randomized prospective cohort study. SETTING: Long-term care facilities.
      PARTICIPANTS: Two hundred seven subjects with stage III or IV pressure ulcers.
      INTERVENTION: Two separate randomized control studies of advanced pressure ulcers
      that compared wound healing on 3 different support surfaces. Subjects were
      allocated to low air loss bed, upgraded bed overlay (only in study 1), or 4h/d
      sitting on an experimental generic total contact seat. The seat was designed
      using prosthetics principles aimed at distributing pressure off bony prominences
      onto less pressure-sensitive areas. Subjects were followed for 6 months or until
      they were totally healed. MAIN OUTCOME MEASURES: Number of subjects who totally
      healed, time to total healing, and pressure ulcer status score after 4 weeks of
      treatment. Interface pressures and functional capacity were also measured at 4
      weeks. RESULTS: In study 1, 3 subjects worsened on the bed overlay condition and
      were withdrawn from the study. None worsened on low air loss or generic total
      contact seat. At 4 weeks in both studies, pressure ulcer status score was lowest
      for the generic total contact seat (P<.0001), compared with the other surfaces.
      Subject populations were similar, so to analyze total healing, results from both
      studies were combined. Total healing of pressure ulcers occurred as early as 4
      weeks in some subjects using the generic total contact seat. Even at 8 weeks,
      total healing was primarily seen with use of that seat, on which interface
      pressures, function, and seating tolerance were best. CONCLUSIONS: Faster healing
      and better function indicate that treatment using the generic total contact seat
      is superior to low air loss bed therapy, which is standard care for advanced
      pressure ulcers.

PMID- 14669177
TI  - A staged management diabetes foot program versus standard care: a 1-year cost and
      utilization comparison in a state public hospital system.
AB  - OBJECTIVE: To determine whether staged management of foot ulcers reduces health
      care costs and utilization. DESIGN: Nonrandomized retrospective study using data
      from 1998-1999 in the Louisiana public hospital system. SETTING: Louisiana public
      hospital system. PARTICIPANTS: Forty-five patients with diabetes foot ulcer who
      received staged management foot care and 169 patients with diabetes foot ulcer
      who received standard foot care. INTERVENTIONS: Staged management of foot ulcers
      consisting of devices to offload pressure; self-care education; and, after
      healing, custom-fabricated orthoses and footwear, and monitored progressive
      ambulation. MAIN OUTCOME MEASURES: One-year levels of the number of foot-related
      inpatient hospitalizations, number of amputation-related hospitalizations, total
      number of foot-related inpatient days, total charges for foot-related inpatient
      hospitalizations, all-cause outpatient visits, total charges for all-cause
      outpatient visits, and combined outpatient and foot-related inpatient charges.
      RESULTS: Over the 12-month study period, the staged management group had a lower
      foot-related hospitalization rate than did the comparison group (.09 admissions
      per person vs.50 admissions per person, P=.0002); lower foot-related inpatient
      days (.91d per person vs 3.97d per person, P=.0289); lower foot-related inpatient
      charges ($1321 per person vs $5411 per person, P=.0151); fewer amputation-related
      hospitalizations (.04 per person vs.19 per person, P=.0351); fewer emergency
      department visits (.60 visits per person vs 1.22 visits per person, P=.0043);
      lower emergency department charges ($104 per person vs $208 per person, P=.0057);
      and lower total charges ($4776 per person vs $9402 per person, P=.0141). The
      staged management group had a higher number of outpatient visits (24.91 per
      person vs 8.04 per person, P<.0001) and higher outpatient charges ($2169 per
      person vs $1471 per person, P<.0001). CONCLUSIONS: A staged management diabetes
      foot program significantly reduced emergency department and hospital utilization
      and charges in a statewide public hospital system.

PMID- 14669178
TI  - Differences in physical performance between men and women with and without
      lymphoma.
AB  - OBJECTIVES: To describe and compare physical performance profiles in men and
      women with lymphoma with age- and gender-matched controls and to examine
      relationships among fatigue severity and physical performance in men and women
      with lymphoma. DESIGN: Case-control study. SETTING: Outpatient lymphoma service
      in a major cancer teaching hospital. PARTICIPANTS: Fifty-one patients with
      lymphoma (26 women, 25 men), age- and gender-matched to 51 subjects without
      lymphoma. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A physical
      performance test battery consisting of a 50-ft (15-m) walk, a 6-minute walk,
      forward reach, repeated sit-to-stand, repeated reach-up, timed belt tie, sock
      test, and coin test. Patients also completed the Brief Fatigue Inventory (BFI).
      RESULTS: Multivariate analysis of variance was significant for main effects of
      group (F(8,89)=27.12, P<.05) and gender (F(8,89)=3.09, P<.05), and there was no
      significant interaction. Subsequent analyses found significant differences
      between groups and gender in the repeated reach-up task, forward reach, 50-ft
      walk, and distance walked in 6 minutes. Correlations among physical performance
      tasks and total BFI interference scores were moderate (r range,.27-.43; P<.05)
      for tasks involving upper extremity, and stronger (r range,.51 to -.73; P<.05)
      for tasks that involved whole-body movements. CONCLUSION: There is a leveling
      effect of lymphoma across gender on most tasks. The significant relations between
      physical performance tasks and fatigue are suggestive of the pervasive influence
      of fatigue on physical function.

PMID- 14669179
TI  - Recovery of standing balance and functional mobility after stroke.
AB  - OBJECTIVE: To examine the extent to which recovery of functional balance and
      mobility is accompanied by change in a few specific physiologic measures of
      postural control. DESIGN: Longitudinal prospective study. SETTING: Laboratory
      setting in Ontario. PARTICIPANTS: Twenty-seven volunteers (age, 64.2+/-13.7y)
      undergoing 4 weeks of rehabilitation after stroke participated. At initial
      testing, patients were 32.7+/-18.4 days poststroke and exhibited a moderate level
      of motor recovery (lower-extremity and postural control, stages 3-4 on the
      Chedoke-McMaster Stroke Assessment Impairment Inventory). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Three functional measures (Berg Balance Scale,
      Clinical Outcome Variables Scale, gait speed) were assessed. Three physiologic
      measures (electromyographic data of hamstrings and soleus muscles bilaterally,
      postural sway, arm acceleration) were taken while subjects stood quietly on a
      force platform and while they performed a rapid shoulder flexion movement of the
      nonparetic upper extremity. RESULTS: After 1 month of rehabilitation, there was
      an overall significant improvement in all outcome measures (functional,
      physiologic). However, 10 patients failed to show any improvement in the
      electromyographic activation of hamstrings muscle on the paretic side in response
      to the rapid arm movement. These patients compensated by increasing the
      anticipatory activation of the nonparetic hamstrings. CONCLUSION: After stroke,
      patients showed improvement in both physiologic and functional measures of
      balance and mobility over a 1-month period. We have identified some patients who
      may be using compensatory strategies to increase function. The factors that may
      predict those patients who are likely to use compensatory strategies awaits
      further study.

PMID- 14669180
TI  - Immediate effects of speed-dependent treadmill training on gait parameters in
      early Parkinson's disease.
AB  - OBJECTIVE: To compare the immediate effects of different training interventions
      on gait parameters in patients with early Parkinson's disease (PD). DESIGN:
      Randomized, multiple intervention crossover pilot study. SETTING: A
      rehabilitation center for adult persons with neurologic disorders. PARTICIPANTS:
      Seventeen patients with early PD (Hoehn and Yahr stages I through III) and gait
      disturbances. INTERVENTION: Patients were randomly assigned to varying sequences
      of the following interventions over 4 consecutive days: structured speed
      dependent treadmill training (STT), limited progressive treadmill training (LTT),
      conventional gait training (CGT), and a control intervention. MAIN OUTCOME
      MEASURES: Basic gait parameters (overground walking speed and stride length at
      self-adapted speeds) and parameters of gait analysis based on vertical ground
      reaction forces. RESULTS: STT and LTT improved all basic gait parameters and the
      double stance duration compared with preintervention values (P<.05). No changes
      were found after CGT and the control intervention (P<.05). Significantly higher
      gains were observed in all basic gait parameters after STT and LTT when compared
      with CGT and the control intervention (P<.05). Additionally, a greater reduction
      of double stance duration was found after STT than after the control intervention
      (P<.001). No significant differences in gains were observed between STT and LTT,
      or between CGT and the control intervention, in all gait parameters. CONCLUSION:
      The main disturbances of gait in PD, namely, speed and stride length, can be
      improved through a single intervention of STT or LTT, but not through CGT and the
      control intervention.

PMID- 14669181
TI  - Treadmill training with partial body-weight support after total hip arthroplasty:
      a randomized controlled trial.
AB  - OBJECTIVE: To compare treadmill training with partial body-weight support (TT
      BWS) and conventional physical therapy (PT) in ambulatory patients with hip
      arthroplasty. DESIGN: Randomized controlled trial. SETTING: Rehabilitation
      center. PARTICIPANTS: Eighty patients with a fully loadable implant who could
      walk independently with crutches after unilateral total hip arthroplasty were
      randomized to receive either TT-BWS (treatment group) or conventional PT
      (controls), for 10 working days. INTERVENTIONS: Each patient received 45 minutes
      of individualized PT, either treadmill training plus PT in the experimental or PT
      alone in the control group. MAIN OUTCOME MEASURES: The Harris score, recorded by
      blind assessors, served as the primary outcome measure. Secondary outcome
      measures were the hip extension deficit, gait velocity, gait symmetry, affected
      hip abductor power; hip abductor amplitude of electromyographic activation; and
      the interval from surgery to abandoning crutches. RESULTS: At the end of
      training, the treatment group's Harris score was 13.6 points higher (P<.0001)
      than the control group's score. Further, hip extension deficit was 6.8 degrees
      less (P<.0001), gait symmetry was 10% greater (P=.001), affected hip abductor was
      stronger (Medical Research Council grades 4.24 vs 3.73; P<.0001), and the
      amplitude of gluteus medius activity was 41.5% greater (P=.001) than those
      measures for controls. Gait velocity did not differ in the 2 groups. These
      significant differences in favor of the treatment group persisted at 3 and 12
      months. The treatment group abandoned crutches sooner than the control group (3
      vs 8wk). In the treatment group, 39 patients finished treatment, 35 appeared at
      3, and 26 at 12 months for follow-up. In the control group, the corresponding
      numbers were 40, 35, and 24 patients, respectively. CONCLUSION: TT-BWS is more
      effective than conventional PT at restoring symmetrical independent walking after
      hip replacement.

PMID- 14669182
TI  - Differential responses to measures of gait performance among healthy and
      neurologically impaired individuals.
AB  - OBJECTIVES: To compare gait during a 5-minute walk among healthy individuals,
      persons with spinal cord injury (SCI), and stroke survivors and to investigate
      whether simultaneous measures of oxygen consumption enhance information about
      performance. DESIGN: Descriptive study. SETTING: Veterans Affairs medical center.
      PARTICIPANTS: Thirty-nine healthy individuals, 10 persons with SCI, and 20 stroke
      survivors. INTERVENTIONS: Participants were fitted with a portable gas analyzer
      and walked on a 5-m walkway for 5 minutes. MAIN OUTCOME MEASURES: Measures of
      walk distance, gait speed, gait energy expenditure (GEE), and gait cost were
      obtained, along with measures of ventilation (.Ve), ventilation and carbon
      dioxide production slope (.Ve . .VCo2), oxygen pulse, and heart rate. RESULTS:
      The SCI group (127.65+/-81.74m) walked less than the stroke survivors (148.80+/
      64.3m) or the healthy group (268.90+/-35.01m) but had higher energy demands, as
      shown by GEE (SCI group, 13.28+/-3.23mL.kg(-1).min(-1); stroke group, 10.18+/
      2.14mL.kg(-1).min(-1); healthy group, 9.61+/-1.90mL.kg(-1).min(-1)) and by gait
      cost (SCI group,.57+/-.40 mL.kg(-1).m(-1); stroke group,.40+/-.52mL.kg(-1).m(-1);
      healthy group,.18+/-.02mL.kg(-1).m(-1)). Compared with the healthy group, the
      stroke group had higher .Ve (stroke group, 22.34+/-5.20L/min vs healthy group,
      16.11+/-3.22L/min) and .Ve . .VCo2 slope (24.22+/-8.80 vs 18.73+/-5.44,
      respectively). CONCLUSION: Use of metabolic assessment during the 5-minute walk
      was feasible and provided further information for evaluating gait performance
      with the subjects studied.

PMID- 14669183
TI  - Cardiorespiratory fitness and walking ability in subacute stroke patients.
AB  - OBJECTIVES: To evaluate the cardiorespiratory fitness of subacute stroke patients
      and to determine whether reduced fitness is associated with gait performance.
      DESIGN: Descriptive, cross-sectional study. SETTING: Rehabilitation hospital.
      PARTICIPANTS: Seventeen patients in an inpatient rehabilitation unit who had mild
      to moderate gait impairments after a recent (< or =7wk) stroke. All subjects
      could walk at least 3m alone or with an aid but with no standby assistance.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Peak and submaximal
      cardiorespiratory responses were measured during semirecumbent leg cycling
      exercise. Walking velocity and endurance were assessed with 10-m and 6-minute
      walk tests, respectively. RESULTS: Peak oxygen uptake (Vo(2)peak) was 1.15+/
      0.36L/min, which was only 50% of the Vo(2)peak reported in the literature for a
      healthy, age-matched group. Maximal walking velocity (1.02+/-0.28m/s) and
      endurance (294.1+/-120.2m) were also approximately 50% of an aged-matched healthy
      group. Pearson product-moment correlations revealed that 6-minute walking
      endurance was strongly associated with self-selected walking velocity (R=.91) and
      measures of peak cardiorespiratory fitness (R=.84). CONCLUSIONS:
      Cardiorespiratory fitness was markedly impaired within 7 weeks after a stroke.
      Although muscle weakness and loss of coordination are the primary impairments
      that affect gait after a stroke, impaired cardiorespiratory fitness may
      secondarily affect gait performance by limiting walking endurance. To address
      this secondary impairment, current rehabilitation interventions can incorporate
      assessment of cardiorespiratory fitness status and aerobic exercise training for
      persons after stroke.

PMID- 14669184
TI  - Arthrographic and clinical findings in patients with hemiplegic shoulder pain.
AB  - OBJECTIVES: To identify the etiology of hemiplegic shoulder pain by arthrographic
      and clinical examinations and to determine the correlation between arthrographic
      measurements and clinical findings in patients with hemiplegic shoulder pain.
      DESIGN: Case series. SETTING: Medical center of a 1582-bed teaching institution
      in Taiwan. PARTICIPANTS: Thirty-two consecutive patients with hemiplegic shoulder
      pain within a 1-year period after first stroke were recruited. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Clinical examinations included Brunnstrom
      stage, muscle spasticity distribution, presence or absence of subluxation and
      shoulder-hand syndrome, and passive range of motion (PROM) of the shoulder joint.
      Arthrographic measurements included shoulder joint volume and capsular
      morphology. RESULTS: Most patients had onset of hemiplegic shoulder pain less
      than 2 months after stroke. Adhesive capsulitis was the main cause of shoulder
      pain, with 50% of patients having adhesive capsulitis, 44% having shoulder
      subluxation, 22% having rotator cuff tears, and 16% having shoulder-hand
      syndrome. Patients with adhesive capsulitis showed significant restriction of
      passive shoulder external rotation and abduction and a higher incidence of
      shoulder-hand syndrome (P=.017). Those with irregular capsular margins had
      significantly longer shoulder pain duration and more restricted passive shoulder
      flexion (P=.017) and abduction (P=.020). Patients with shoulder subluxation had
      significantly larger PROM (flexion, P=.007; external rotation, P<.001; abduction,
      P=.001; internal rotation, P=.027), lower muscle tone (P=.001), and lower
      Brunnstrom stages of the proximal upper extremity (P=.025) and of the distal
      upper extremity (P=.001). Muscle spasticity of the upper extremity was slightly
      negatively correlated with shoulder PROM. Shoulder joint volume was moderately
      positively correlated with shoulder PROM. CONCLUSIONS: After investigating the
      hemiplegic shoulder joint through clinical and arthrographic examinations, we
      found that the causes of hemiplegic shoulder pain are complicated. Adhesive
      capsulitis was the leading cause of shoulder pain, followed by shoulder
      subluxation. Greater PROM of the shoulder joint, associated with larger joint
      volume, decreased the occurrence of adhesive capsulitis. Proper physical therapy
      and cautious handling of stroke patients to preserve shoulder mobility and
      function during early rehabilitation are important for a good outcome.

PMID- 14669185
TI  - Reliability of a road test after stroke.
AB  - OBJECTIVE: To determine the reliability of the road test performed by stroke
      patients. DESIGN: Prospective study of a 6-month predriving evaluation. SETTING:
      Driving safety center in Belgium. PARTICIPANTS: Thirty patients with sequelae of
      stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Results of driving
      performance as judged by 2 assessors from the Center for Determination of Fitness
      to Drive and Car Adaptations (CARA), in a car fitted with a video camera. A third
      assessor also evaluated all the video recordings. Interrater reliability was
      evaluated by comparing results from real-life performance and video recording, as
      judged by the CARA assessors and video judgments between CARA assessors and the
      third assessor. RESULTS: Most subitems of the road test showed more than 80%
      scoring agreement between the various evaluations. Intraclass correlation
      coefficients (ICCs) of the items varied from -.08 to 1.0. The ICC of the overall
      performance was.62 when real-life scores were compared with video evaluations
      and.80 in video versus video comparison. CONCLUSION: The reliability of assessing
      overall performance of stroke patients in the road test is moderately high and
      better when assessed using the same evidence. Yet, the reliability of some items
      needs further attention.

PMID- 14669186
TI  - Tips and falls during electric-powered wheelchair driving: effects of seatbelt
      use, legrests, and driving speed.
AB  - OBJECTIVE: To measure the response of a test dummy while traversing common
      obstacles encountered by users of electric-powered wheelchairs (EPWs) to
      determine whether optimal wheelchair fit, use of seatbelts, and driving speed
      affect the frequency and severity of EPW tips and falls. DESIGN: Repeated
      measures comparison study. SETTING: Constructed environment both in and around a
      Veterans Affairs medical center. PARTICIPANT: A 50th percentile Hybrid II
      anthropometric test dummy (ATD) was used to simulate a person driving an EPW.
      INTERVENTIONS: The ATD was driven in 4 different EPWs over commonly encountered
      obstacles at speeds of 1 and 2m/s, with and without the use of a seatbelt, and at
      varying legrest heights. MAIN OUTCOME MEASURES: The response and motion of the
      ATD were observed and recorded as no fall, loss of control (the ATD falls forward
      or sideways but remains in the EPW), the ATD falls out of the EPW, or the EPW
      tips completely. RESULTS: A total of 97 adverse events out of 1700 trials were
      recorded: 88 were losses of control (instability) and 9 were ATD falls. No
      complete tips of any EPW occurred. Univariate statistical analysis indicated a
      significant relationship between the adverse events and the use of seatbelts,
      legrest condition, and test obstacles (P<.05). A mixed-model analysis confirmed
      the significant relationships between the adverse events and the use of
      seatbelts, legrest condition, and test obstacles (P<.05). However, the mixed
      model indicated that (1) there was no significant relationship between the
      adverse events and driving speed and (2) no one obstacle was designated to be the
      most problematic. CONCLUSION: Persons who use EPWs should use seatbelts and
      legrests while driving their EPWs, and clinicians should include common driving
      tasks when assessing the proper set-up of EPWs.

PMID- 14669187
TI  - Validation of a model for evaluating outcome after traumatic brain injury.
AB  - OBJECTIVE: To validate a model that examines the contribution of premorbid
      variables, injury severity, and functional and cognitive status to outcome 1 year
      after traumatic brain injury (TBI). DESIGN: Cross-validation study using a
      larger, national, prospective, longitudinal sample. SETTING: Acute inpatient
      rehabilitation hospitals at Traumatic Brain Injury Model Systems centers.
      PARTICIPANTS: Two sample populations followed through acute rehabilitation to 1
      year after TBI. The original sample included 107 patients, and the cross
      validation sample included 294 patients. Participants were predominantly young
      men who had experienced moderate to severe TBI in motor vehicle crashes.
      INTERVENTIONS: Acute medical and rehabilitation care. MAIN OUTCOME MEASURES:
      Disability Rating Scale, Community Integration Questionnaire, and return to
      employment. RESULTS: Structural equation modeling was used to compare the fit of
      the data to a path analysis developed through clinical use and previous research.
      Both samples provided adequate goodness of fit, supporting the model's validity.
      Injury severity affected cognitive and functional status, and cognitive and
      functional status significantly influenced 1-year outcome. Premorbid factors and
      injury severity did not directly influence outcome. CONCLUSIONS: Both samples
      supported the proposed model, which was cross-validated. Injury severity
      indirectly influences outcome through its effects on cognitive and functional
      status. Although treatment to decrease injury severity is obviously important,
      concentrated rehabilitation interventions aimed at improving patients' cognitive
      and functional status may have a more significant impact on 1-year outcome and
      should be the focus of future research.

PMID- 14669188
TI  - Spasticity in adults living in a developmental center.
AB  - OBJECTIVES: To ascertain the prevalence of spasticity among adults living in a
      developmental center and to document the development of spasticity treatment
      plans for this population. DESIGN: Descriptions of the clinical features of
      medical disorders and a prevalence survey. SETTING: Residential developmental
      center. PARTICIPANTS: One hundred three adults. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Characteristics described included the prevalence of
      spasticity in this population, the specific spasticity diagnosis, functional
      goals for spasticity treatment identified by the participants' multidisciplinary
      teams, and the specific treatment indicated by the neurologist. RESULTS: Of the
      103 people diagnosed by the neurologist, 24 had diplegic spasticity, 4 had
      hemiplegic spasticity, 44 had quadriplegic spasticity, and 31 had no spasticity.
      Functional goals identified by multidisciplinary teams were undergarment change
      (46.3% of the persons for whom goals were identified), splinting hands (11%),
      dressing (57.4%), hygiene (20.4%), wheelchair positioning (25.9%), ambulation
      improvement (14.8%), and transfers (9.3%). After physical and occupational
      therapy, the first invasive treatments indicated for people with spasticity
      included botulinum toxin injections (60%), intrathecal baclofen (26.4%),
      orthopedic surgery (5.6%), and medication (1.4%). No treatment was recommended
      for 25% of the spasticity patients. CONCLUSIONS: The prevalence of spasticity was
      35% in this developmental center population of 205 individuals. A
      multidisciplinary team approach to the evaluation of adults with spasticity who
      live in a developmental center makes it possible to identify functional goals
      that are amenable to spasticity treatment and minimizes treatment that does not
      target specific functional goals.

PMID- 14669189
TI  - The Montreal Rehabilitation Performance Profile: a statistical model for
      assessing stair descent in children with cognitive impairments.
AB  - OBJECTIVES: To characterize the responsiveness of the Montreal Rehabilitation
      Performance Profile (MRPP); to measure the differential effectiveness of a task
      specific (TS) and a task-nonspecific (TNS) motor learning format to promote
      alternating stair descent in children with cognitive impairments; and to evaluate
      the relevance of the MRPP to evidence-based practice. DESIGN: Randomized
      comparison of 2 age-matched groups; psychometric testing of measurement tool.
      SETTING: School for children with developmental and cognitive impairments.
      PARTICIPANTS: Ambulatory sample of convenience: 18 children, age 5 to 9 years,
      with moderate to severe cognitive impairment. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: The MRPP variables measured at baseline; end of 10-week
      intervention; and 5 and 10 weeks postintervention. Analysis of variance for
      repeated measures and part-whole correlation. RESULTS: Global stair descent
      performance improved for both TS and TNS groups over time (P=.001). However, a
      specific acquisition and retention of the alternating pattern of descent was
      associated with the TS format. CONCLUSION: The MRPP was responsive to small
      differences in stair descent performance that are specific to the format of the
      motor learning intervention. The MRPP allows clinicians to determine the timing
      of the intervention needed to maintain or improve stair descent ability.

PMID- 14669190
TI  - Health behaviors, body composition, and coronary heart disease risk in women with
      multiple sclerosis.
AB  - OBJECTIVES: To explore coronary heart disease risk in a sample of women with
      multiple sclerosis (MS) by identifying the presence of established risk factors
      for coronary heart disease and to determine the relationship between disease
      severity and level of participation in health-related behaviors. DESIGN: Survey
      study. SETTING: Five general community settings in Oregon. PARTICIPANTS: Women
      with physician-diagnosed MS (N=123) recruited from MS chapters, physician
      referrals, and newspaper announcements. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Modified Yale Physical Activity Survey, Block Food Frequency
      Questionnaire, blood analysis, skinfolds, and waist and hip circumferences.
      RESULTS: The majority of women met current physical activity guidelines. The
      frequencies of unfavorable levels of metabolic variables and obesity were similar
      to those reported in the general population. Significant associations were
      observed between mobility and physical activity, total and abdominal fat, and
      several dietary habits. CONCLUSION: Coronary heart disease risk in this sample
      was comparable to that of the general population of women without MS. Physical
      inactivity, body composition, and perhaps nutritional habits decline with
      decreasing mobility, emphasizing the need for families and health care providers
      to work together to find solutions that increase health-promoting behaviors in
      women with more advanced MS.

PMID- 14669191
TI  - Impaired oxygen on-kinetics in persons with human immunodeficiency virus are not
      due to highly active antiretroviral therapy.
AB  - OBJECTIVE: To determine the effects of human immunodeficiency virus (HIV) and
      highly active antiretroviral therapy (HAART) on oxygen on-kinetics in HIV
      positive persons. DESIGN: Quasi-experimental cross-sectional. SETTING: Infectious
      disease clinic and exercise laboratory. PARTICIPANTS: Referred participants
      (N=39) included 13 HIV-positive participants taking HAART, 13 HIV-positive
      participants not taking HAART, and 13 noninfected controls. INTERVENTIONS:
      Participants performed 1 submaximal exercise treadmill test below the ventilatory
      threshold, 1 above the ventilatory threshold, and 1 maximal treadmill exercise
      test to exhaustion. MAIN OUTCOME MEASURES: Change in oxygen consumption
      (Delta.VO2) and oxidative response index (Delta.VO2/mean response time). RESULTS:
      Delta.VO2 was significantly lower in both HIV-positive participants taking
      (946.5+/-68.1mL) and not taking (871.6+/-119.6mL) HAART than in controls
      (1265.3+/-99.8mL) during submaximal exercise above the ventilatory threshold. The
      oxidative response index was also significantly lower (P<.05) in HIV-positive
      participants both taking (15.0+/-1.3mL/s) and not taking (15.1+/-1.7mL/s) HAART
      than in controls (20.8+/-2.1mL/s) during exercise above the ventilatory
      threshold. CONCLUSION: Oxygen on-kinetics during submaximal exercise above the
      ventilatory threshold was impaired in HIV-positive participants compared with a
      control group, and it appeared that the attenuated oxygen on-kinetic response was
      primarily caused by HIV infection rather than HAART.

PMID- 14669192
TI  - Physician referrals to physical therapy for the treatment of musculoskeletal
      conditions.
AB  - OBJECTIVES: To identify factors associated with orthopedic surgeons' and primary
      care physicians' referrals to physical therapy (PT) for musculoskeletal
      conditions. DESIGN: Cross-sectional analysis of National Ambulatory Medical Care
      Survey data. SETTING: US office-based physician practices. PARTICIPANTS: Visits
      to primary care physicians (N=4911) or orthopedic surgeons (N=4201) for
      musculoskeletal conditions. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Whether a PT referral was made. RESULTS: After controlling for diagnosis, illness
      severity, and PT supply, insurance status and physician characteristics remained
      strong predictors of PT referral. Primary care visits covered by Medicaid or a
      managed care plan were less likely to result in PT referral than were visits
      covered by private insurance or a nonmanaged care plan. Orthopedic surgeon visits
      covered by workers' compensation or managed care were more likely to result in PT
      referral than were visits not covered by workers' compensation or not covered by
      managed care. Osteopathic primary care visits were more likely than allopathic
      primary care visits to result in PT referral. Given identical visit
      characteristics, orthopedic surgeon visits were more likely than primary care
      visits to result in PT referral. CONCLUSIONS: Significant differences exist in
      orthopedic surgeons' and primary care physicians' referrals to PT, both within
      and across specialties. Variation in PT referral may be indicative of problems
      with access and/or inappropriate referral.

PMID- 14669193
TI  - Effectiveness of electric stimulation of the vastus medialis muscle in the
      rehabilitation of patients after total knee arthroplasty.
AB  - OBJECTIVE: To investigate the possible effect of electric muscle stimulation
      (EMS) of the vastus medialis on the walking speed, Hospital for Special Surgery
      (HSS) knee score, and Physiological Cost Index (PCI) of patients during
      rehabilitation after total knee arthroplasty (TKA). DESIGN: Prospective,
      randomized controlled trial. SETTING: Various departments at a district general
      hospital in the United Kingdom. PARTICIPANTS: Thirty patients with unilateral
      osteoarthritis of the knee admitted for elective TKA were randomly assigned to 1
      of 2 groups (15 per group): control and treatment. Both groups received standard
      physical therapy. The treatment group also received EMS of the vastus medialis.
      INTERVENTION: EMS (40Hz, 300micros) of the vastus medialis muscle for 4 hours a
      day, starting on postoperative day 2, over the first 6 postoperative weeks. MAIN
      OUTCOME MEASURES: Changes in walking speed, HSS knee score, and effort of walking
      as measured by the PCI. RESULTS: A statistically significant increase in walking
      speed was observed in the treatment group in relation to the control group at
      both 6 weeks (P=.0002) and 12 weeks (P<.0001) postoperatively. No statistically
      significant difference was observed in relation to the PCI or the HSS knee score
      variables. CONCLUSIONS: Application of EMS after TKA resulted in a statistically
      significant improvement in patients' walking speed. There was also a carry-over
      effect after the discontinuation of treatment.

PMID- 14669194
TI  - High-frequency vibration training increases muscle power in postmenopausal women.
AB  - OBJECTIVE: To test whether training on a high-frequency (28Hz) vibrating platform
      improves muscle power and bone characteristics in postmenopausal women. DESIGN:
      Randomized controlled trial with 6-month follow-up. SETTING: Outpatient clinic in
      a general hospital in Italy. PARTICIPANTS: Twenty-nine postmenopausal women
      (intervention group, n=14; matched controls, n=15). INTERVENTION: Participants
      stood on a ground-based oscillating platform for three 2-minute sessions for a
      total of 6 minutes per training session, twice weekly for 6 months. The controls
      did not receive any training. Both groups were evaluated at baseline and after 6
      months. MAIN OUTCOME MEASURES: Muscle power, calculated from ground reaction
      forces produced by landing after jumping as high as possible on a forceplate,
      cortical bone density, and biomarkers of bone turnover. RESULTS: Over 6 months,
      muscle power improved by about 5% in women who received the intervention, and it
      remained unchanged in controls (P=.004). Muscle force remained stable in both the
      intervention and control groups. No significant changes were observed in bone
      characteristics. CONCLUSION: Reflex muscular contractions induced by vibration
      training improve muscle power in postmenopausal women.

PMID- 14669195
TI  - Interrater reliability of clinical examination measures for identification of
      lumbar segmental instability.
AB  - OBJECTIVE: To determine the interrater reliability of common clinical examination
      procedures proposed to identify patients with lumbar segmental instability.
      DESIGN: Single group repeated-measures interrater reliability study. SETTING:
      Outpatient physical therapy (PT) clinic and university PT department.
      PARTICIPANTS: A consecutive sample of 63 subjects (38 women, 25 men; 81% with
      previous episodes of low back pain [LBP]) with current LBP was examined by 3
      pairs of raters. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Repeat
      measurements of clinical signs and tests proposed to identify lumbar segmental
      instability. RESULTS: Kappa values for the trunk range of motion (ROM) findings
      varied (range,.00-.69). The prone instability test (kappa=.87) showed greater
      reliability than the posterior shear test (kappa=.22). The Beighton Ligamentous
      Laxity Scale (LLS) for generalized ligamentous laxity showed high reliability
      (intraclass correlation coefficient=.79). Judgments of pain provocation (kappa
      range,.25-.55) were generally more reliable than judgments of segmental mobility
      (kappa range, -.02 to.26) during passive intervertebral motion testing.
      CONCLUSIONS: The results agree with previous studies suggesting that segmental
      mobility testing is not reliable. The prone instability test, generalized LLS,
      and aberrant motion with trunk ROM demonstrated higher levels of reliability.

PMID- 14669196
TI  - The effects of added prosthetic mass on physiologic responses and stride
      frequency during multiple speeds of walking in persons with transtibial
      amputation.
AB  - OBJECTIVES: To determine the effect of 3 prosthetic mass conditions on selected
      physiologic responses during multiple speed treadmill walking in persons with
      transtibial amputation. DESIGN: A repeated-measures design for 3 prosthetic mass
      conditions and 5 walking speeds. SETTING: University research laboratory.
      PARTICIPANTS: Eight ambulatory men with unilateral traumatic transtibial
      amputation. INTERVENTIONS: The 3 prosthetic mass conditions were 60%, 80%, and
      100% of the estimated intact limb below-knee mass. The multiple-speed treadmill
      walking test (4min at each speed: 54, 67, 80, 94, 107m/min) was performed on an
      instrumented treadmill according to randomly assigned mass conditions. MAIN
      OUTCOME MEASURES: Oxygen consumption, gait efficiency, relative exercise
      intensity (percentage of age-predicted maximal heart rate), and stride frequency.
      RESULTS: Prosthetic mass did not significantly alter oxygen consumption or gait
      efficiency (P>.05). From the 60% to the 100% prosthetic mass conditions, relative
      exercise intensity significantly increased and stride frequency significantly
      decreased (P<.05). CONCLUSIONS: A heavier prosthesis (up to 100% of estimated
      intact limb below-knee mass) did not significantly increase the energy costs of
      walking for the 5 speeds examined. Further study of gait symmetry with the use of
      a heavier prosthesis is warranted.

PMID- 14669197
TI  - Gender differences in the performance of activities of daily living.
AB  - OBJECTIVES: To verify that the activities of daily living (ADL) motor and process
      skill items and tasks in the Assessment of Motor and Process Skills (AMPS) are
      free from gender bias, and to compare mean differences in ADL motor and process
      ability between men and women. DESIGN: Descriptive comparison; convenience
      sample. SETTING: Existing data from the AMPS database. PARTICIPANTS: Potential
      participants included nonwell persons (age range, 18-99y) matched within 3 age
      groups, first by functional level and then by diagnostic category. The resulting
      sample included 9250 men and 9250 women. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: The AMPS, a standardized observational assessment of the
      quality of ADL task performance. RESULTS: None of the AMPS task calibrations and
      1 motor skill item calibration (Lifts) demonstrated an observable difference
      between men and women. Men had higher ADL motor ability (F(1,18494)=11.58, P<.01)
      and women had higher ADL process ability (F(1,18494)=76.18, P<.01). CONCLUSION:
      The results suggest that the AMPS is free of gender bias. Although differences
      were found between men and women in mean ADL motor and process ability, they were
      not considered clinically detectable differences.

PMID- 14669198
TI  - The status of gait assessment among physiotherapists in the United Kingdom.
AB  - OBJECTIVES: To evaluate how physiotherapists are trained in and use clinically
      orientated gait assessment tools and instrumented gait analysis, and to identify
      if a need exists for a standardized methodology. DESIGN: Survey. SETTING: UK
      National Health Service. PARTICIPANTS: Physiotherapists working with a variety of
      patient groups in 210 randomly selected Health Care Trusts. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Amount of gait assessment training, frequency
      of gait laboratory use, types and frequency of standardized gait assessment tools
      used, and expressed need for a gait assessment tool in clinical practice.
      RESULTS: A total of 1826 (43.5%) physiotherapists responded. Management of
      abnormal gait constituted a major aspect of physiotherapy practice; yet, there
      was no systematic use of standardized gait assessment tools. Gait video images
      were typically collected and analyzed without the use of standardized protocols.
      Only 23.1% of all respondents had a patient assessed in a gait laboratory.
      Clinicians indicated that they need training in gait assessment (66.4%) and
      desire guidance at a national level. Exactly 91.8% of physiotherapists requested
      a new gait assessment tool that can be used easily and quickly within a busy
      schedule without compromising reliability and validity. CONCLUSIONS: Gait
      assessment plays a pivotal role for physiotherapists managing gait problems. The
      challenge for developers of gait assessment tools is to find a balance between
      the practicalities of use and scientific merit.

PMID- 14669199
TI  - Contemporary issues in mild traumatic brain injury.
AB  - OBJECTIVES: To determine (1) minimum criteria in adults for clinical diagnosis of
      mild traumatic brain injury (TBI) and (2) whether persistent postconcussive
      syndrome exists as a nosologic entity. DATA SOURCES: PubMed search by MEDLINE of
      head injuries from January 1977 to July 2002. STUDY SELECTION: All reviews and
      studies of mild TBI with special reference to those on persistent postconcussive
      syndrome having a general trauma cohort as a control comparison. DATA EXTRACTION:
      Review of design and other methodologic issues. Studies dependent on superior
      strength of evidence (as defined by the American Academy of Neurology) concerning
      the biologic nature of persistent postconcussive syndrome. DATA SYNTHESIS: A
      period of altered awareness with amnesia brought on by a direct craniofacial blow
      is the starting point in determining whether diffuse mild TBI has occurred. An
      amnestic scale is more helpful than Glasgow Coma Scale score in grading mild
      injury and in formulating minimum inclusion criteria for mild TBI.
      Neuropsychologic test results coupled with self-reported symptoms should not be
      taken as the primary source of evidence for mild TBI. Prolonged cognitive
      impairment after injury is not unique to brain trauma. CONCLUSIONS: Persistent
      postconcussive syndrome after mild brain trauma, uncomplicated by focal injury,
      is biologically inseparable from other examples of the posttraumatic syndrome. To
      account for the persistent cognitive and behavioral sequelae of posttraumatic
      states, including persistent postconcussive syndrome, we need further studies on
      the emerging concept of limbic neuronal attrition occurring as a maladaptive
      response to pain and stress.

PMID- 14669200
TI  - Development of the concepts of knee kinematics.
AB  - OBJECTIVES: To review the experimental evidence and development of concepts in
      knee kinematics and to present a synthesis of current theories. DATA SOURCES:
      Historical literature from private collections and published journals, from Galen
      in 160 AD, and Weber and Weber in 1860, through to current research in knee
      kinematics, sourced through MEDLINE and CINAHL. STUDY SELECTION: Studies of the
      healthy human knee in vivo and in vitro were included. Other studies were
      included when relevant, for example, when knee surgery methods have led to a
      change in kinematic concepts. Of 285 items, 94 were included based on their
      contribution to original research. When relevant, authors were contacted to
      resolve issues. DATA EXTRACTION: Sources included were descriptive studies,
      anatomic dissections, controlled experimental designs, editorials, and review
      articles. DATA SYNTHESIS: The axes of rotation of the knee are fundamental to
      kinematic models. The hinge model is contradicted by the ellipsoid shape of the
      femoral condyles, which results in a moving instant center of motion. However,
      the "instant center of motion" model was based on analysis of sagittal sections,
      oblique to the plane of movement and neglecting rotation. The four-bar linkage
      theory linked cruciate ligament isometry with the roll and glide pattern of knee
      motion. Recently, however, studies of the biomechanics and histology of the knee
      ligaments have enabled more accurate kinematic modeling. Three-dimensional
      imaging and computer modeling have made possible analysis of kinematics parallel
      to the planes of motion and incorporation of conjoint rotation. Femoral roll back
      is now described as the manifestation of longitudinal rotation during knee
      flexion. CONCLUSIONS: Current research concludes that the knee has 4 independent
      axes: patella, posterior condylar, distal condylar, and longitudinal axes. The
      axes combine to produce the characteristic helical motion of the knee.

PMID- 14669201
TI  - Treatment of testicular pain using conservative management of the thoracolumbar
      spine: a case report.
AB  - Unsuccessful recognition of the origin of testicular pain and a high failure rate
      of surgical interventions lead to poor outcomes, psychologic distress, and
      increased costs of care. A frequently overlooked cause of testicular and buttock
      pain is irritation of the T10-L1 sensory nerve roots, the genitofemoral nerve,
      and the ilioinguinal nerve. We present the case of a 36-year-old policeman with a
      5-year history of back pain and testicular pain of unknown origin. Physical
      examination of the thoracolumbar region revealed that active movement provoked
      the patient's buttock symptoms, and local mobility restrictions were present in
      the thoracolumbar region. A central disk protrusion at T12-L1 was noted on upper
      lumbar spine magnetic resonance imaging, which supports dysfunction of this
      region. The diagnosis of thoracolumbar stiffness led to implementation of passive
      and active mobilization of that region and to specific hip stretching and
      strengthening exercises. After a course of direct and guided physical therapy,
      the patient attained complete symptom resolution. The patient returned to full
      work duties as a police officer and resumed his full recreational activity. The
      excellent outcome achieved in managing this patient was attributed to identifying
      the origin of referred pain from the thoracolumbar junction.

PMID- 14669202
TI  - Vocal fold paralysis and electromyography.

PMID- 14669211
TI  - [A rare transcription mutation (-90 C-->T) in a Chinese family with beta
      thalassemia].
AB  - OBJECTIVE: To identify a rare transcription mutation (C-->T) at position -90 of
      the beta-globin gene previously unreported in the beta-thalassemia carriers from
      a Chinese family. METHODS: In phenotype analysis, standard hematological
      techniques were used to measure RBC counts and Hb concentration. Reverse dot blot
      (RDB) analysis, which can simultaneously detect 18 known types of beta
      thalassemia mutations in Chinese, was used to scan beta-globin gene mutations.
      DNA sequence analysis of the entire human beta-globin gene was performed to
      characterize the underlying causative mutation of the sample and to identify its
      genotype. A semi-quantitative RT-PCR method was used to measure beta-globin gene
      expression in the form of mRNA from the subjects. RESULTS: The proband, his
      brother and his mother presented a typical beta-thalassemic trait with reduced
      mean corpuscular volume (MCV, 68.2-73.6 fL) and elevated level of Hb A(2) (5.7%
      6.4%) but no known beta-thalassemia mutations were found in the samples by RDB
      analysis. DNA sequencing of the beta-gene region of these three samples revealed
      heterozygosity for the C-->T substitution at position -90 within proximal CACCC
      box of the beta-globin gene promoter element, which was previously unreported in
      the Chinese population. Analysis of mRNA from the positive carriers demonstrated
      that the mutant beta-globin gene significantly reduced beta-globin transcription
      (mutants: 2.233 +/- 0.01 vs normal: 3.779+/-1.19; 95%CI: 3.060, 4.499), showing a
      level comparable with that of the other beta-thalassemia heterozygotes (2.110+/
      0.53, 95%CI: 1.732, 2.488). CONCLUSION: A rare transcriptional mutation that led
      to beta-thalassemia in Chinese population has been characterized. The findings
      enrich knowledge of the mutation spectrum of beta-thalassemia.

PMID- 14669210
TI  - [Association of single nucleotide polymorphism in human SCN7A gene with essential
      hypertension in Chinese].
AB  - OBJECTIVE: To identify the single nucleotide polymorphisms (SNPs) in the
      regulatory and coding regions of human SCN7A (sodium channel, voltage-gated, type
      VII, alpha polypeptide) gene and to investigate the association of some of these
      SNPs with essential hypertension (EH) in Chinese. METHODS: The promoter region,
      exons, as well as part of the introns of SCN7A gene were sequenced by a
      fluorescent labeling automatic sequencing method to identify and characterize the
      SNPs in Chinese population. SNP genotyping was performed by PCR-RFLP or direct
      DNA sequencing in unrelated EH patients and normotensive controls from a Chinese
      Han population residing in Shanghai area. Case-control studies on seven SNPs were
      first carried out in 96 patients and 96 normotensive controls. The positive
      finding was further verified in an extended study containing 288 patients and 288
      controls. RESULTS: Thirty-two SNPs were identified through a 13,132 bp sequencing
      of SCN7A gene. Among them, seven were in regulatory region, ten in coding
      regions, one in 3'UTR and fourteen in introns. Thirty SNPs were novel SNPs, and a
      cSNP in exon 18 (SNP021) was associated with hypertension. CONCLUSION: The SNP021
      in the gene SCN7A is associated with essential hypertension of Chinese Han
      population in Shanghai and the role of SCN7A gene in hypertension deserves to be
      further analyzed.

PMID- 14669212
TI  - [Molecular cytogenetic analysis of -7/7q- abnormalities in patients with myeloid
      malignancies].
AB  - OBJECTIVE: To accurately evaluate the incidence of -7/7q- abnormality in acute
      myeloblastic leukemia (AML) and myelodysplastic syndrome (MDS) patients and
      investigate the value of fluorescence in situ hybridization (FISH) technique in
      the detection and identification of -7 and 7q abnormality. METHODS: A FISH assay
      was performed to analyze 70 AML/MDS patients who had received conventional
      cytogenetic analysis (CCA). The dual color probes CEP 7 labeled by SpectrumGreen
      and D7S486 (locus at 7q31) labeled by SpectrumOrange were used. RESULTS: The
      incidence of -7/7q- in AML and MDS patients was 4.51% (31 out of 687 cases) and
      5.71% (28 out of 490 cases), respectively, and was 5.68% and 10.29% in these
      patients with abnormal karyotype, respectively. The common deletion region of 7q-
      was 7q21a222 (ten cases) and 7q31-35(ten cases). FISH assay confirmed the -7/7q-
      aberration in those with clonal -7/7q- abnormalities, but failed in those with
      random -7/7q- and normal karyotype. In 7q- group, FISH revealed seven of eleven
      cases with monosomy 7 clone detected in the same specimen, but the numbers of 7q-
      interphases cells were much greater than those of monosomy 7 cells (average 42.5%
      vs 8.4%, P=0.025). FISH also provided precise refinement for three chromosomal
      structural abnormalities associated with 7q seen in CAA, one case with
      del(7)(q22) being refined as chromosomal translocation, one case with 7q+ being
      confirmed as dup(7q), and one case with complex translocation involving 7q being
      also proved to be true. CONCLUSION: FISH is a powerful tool to identify or refine
      chromosomal structural aberrations involving 7q, and it provides accurate
      evaluation of -7/7q- in all the patients. -7 and 7q- clone frequently coexist in
      the same specimen, and the significantly increasing percentage of 7q- cells
      implies that -7 clone secondary to 7q- clone is a result from loss of 7q-.

PMID- 14669213
TI  - [Deoxyribonuclease I gene expression in systemic lupus erythematosus patients].
AB  - OBJECTIVE: To observe whether deoxyribonuclease I (DNASE1) gene expression and
      its DNASE1 mRNA expression was detected by real-time polymerase chain reaction
      and its alternatively spliced transcripts were performed by capillary
      electrophoresis. An analysis was also made to disclose whether specific single
      nucleotide polymorphisms (SNPs) haplotype had effects onDNASE1 gene expression
      and its alternatively spliced transcripts. RESULTS: DNASE1 gene expression was
      higher in SLE patients than in normal controls (P<0.001), and in patients it was
      found to be of no relationship with SLE disease activity index score. However, it
      was increased in female patients. Capillary electrophoresis revealed that the
      pattern of alternatively spliced transcripts in patients was not the same as that
      in normal controls. Moreover, it seemed that different SNPs haplotype combination
      might show different transcript pattern in SLE patients. CONCLUSION: In SLE
      patients, DNASE1 gene expression is abnormal and there are alternatively spliced
      transcripts different from those in normal controls. DNASE1 gene is a critical
      factor in the pathogenesis of SLE.

PMID- 14669214
TI  - [A novel mutation of KCNQ2 gene in a Chinese family with benign familial neonatal
      convulsions].
AB  - OBJECTIVE: To diagnose a Chinese benign familial neonatal convulsions (BFNC)
      family at the level of gene and investigate its molecular pathogenesis. METHODS:
      All family members were studied by clinical examinations and linkage analysis.
      Mutation analysis of KCNQ2 gene was made by means of polymerase chain reaction
      (PCR)-direct sequencing and PCR-single strand conformation polymorphism (SSCP) in
      the proband, 16 family members and 72 unrelated normal individuals. RESULTS:
      Linkage analysis hinted the linkage of BFNC to KCNQ2, while the linkage to KCNQ3
      was excluded. Mutation 1931delG of KCNQ2 gene was found in the proband by DNA
      direct sequencing. The same SSCP variant as the proband's was showed in the rest
      affected members of this family but not in the unaffected members of this family
      and all of the 72 unrelated normal individuals. CONCLUSION: 1931delG of KCNQ2
      gene can cause BFNC in China and is novel mutation. The combination of linkage
      analysis and gene analysis is useful for gene diagnosis.

PMID- 14669215
TI  - [Autosomal dominant congenital nuclear cataract caused by a deletion mutation in
      the beta A1-crystallin gene].
AB  - OBJECTIVE: To identify the genetic defect causing automosal dominant congenital
      cataracts (ADCC) with nuclear opacities in a Chinese pedigree. METHODS: Linkage
      analysis was carried out with the short tandem repeat polymorphisms flanking the
      candidate genes. Mutation analysis of the candidate gene in the critical region
      was performed to detect the potential mutation. RESULTS: The cataract locus in
      this pedigree was mapped to 17q11.1-12, an 11.78 cM interval between markers
      D17S933 and D17S 1288. By means of sequencing the candiate gene, betaA1
      crystallin (CRYBA1), a deletion mutation DeltaG91 in exon 4 was detected. This
      change cosegregated with the patients in the family but was not found in 50
      normal unrelated individuals. CONCLUSION: It is a deletion mutation DeltaG91 of
      CRYBA1 gene that causes autosomal dominant congenital nuclear cataract. This is
      the first report of an autosomal dominant congenital nuclear cataract caused by
      the mutation in this gene.

PMID- 14669216
TI  - [Antiestrogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the gene
      expression of insulin-like growth factors family in osteoblast cells].
AB  - OBJECTIVE: To investigate the antiestrogenic effect of environment teratogen on
      the gene expression of insulin-like growth factors (IGFs) family in osteoblast
      cells during rat skeleton development. METHODS: The fetal rat models with
      congenital skeleton malformation were constructed by treating 20 female Wistar
      rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on pregnant day 10. The MC
      3T3-E1 cells were cultured with estrogen, TCDD, or a combination of the two
      chemicals for 24 hours. The IGF-II and IGFBP-6 mRNA levels in rat calvaria bone
      tissue and MC-3T3-E1 cells were detected by reverse transcription-polymerase
      chain reaction. Flow cytometer was used to determine the cell proliferation.
      RESULTS: TCDD at the concentration of 5-15 microg/kg induced developmental
      skeleton defect of fetal rat, and the effect was dose-dependent. The expression
      of IGF-II mRNA gene was enhanced by estrogen in rat calvaria bone tissue and MC
      3T3-E1 cells, whereas IGFBP-6 mRNA was decreased. Estrogen increased the cell
      proliferation in MC-3T3-E1 cells. TCDD, however, inhibited the effect of estrogen
      on regulation of IGF-II gene and IGFBP-6 gene as well as MC-3T3-E1 cell
      proliferation. CONCLUSION: These findings provide the evidence that TCDD can
      induce congenital fetal skeleton malformation under the condition of high
      estrogen level in pregnant Wistar rats. TCDD has antiestrogenic effect and hence
      exerts negative influence on the osteoblast cells through target IGF-II and IGFBP
      6 of IGFs family.

PMID- 14669217
TI  - [One base deletion of the alpha(1,4) galactosyltransferase gene responsible for p
      phenotype].
AB  - OBJECTIVE: To study the molecular genetic basis for p phenotype. METHODS: Red
      blood cell phenotype of the proband was characterized by standard serological
      technique. Exon 3 of the alpha (1,4) galactosyltransferase gene was amplified by
      polymerase chain reaction from genomic DNA of the proband. The amplified PCR
      products were excised and purified from agarose gels and direct sequenced.
      RESULTS: Homozygous single nucleotide G deletion at position 300 or 301 was found
      in the proband, which caused a reading frame shift at codon 101,resulting in a
      premature stop at codon 113. Parents of the proband were heterozygous carriers.
      CONCLUSION: A novel single guanosine deletion at position 300 or 301 of alpha
      (1,4) galactosyltransferase gene was determined, which may be one facet of the
      molecular basis for p phenotype.

PMID- 14669218
TI  - [Effect of SH2A gene in cell signal transduction and its subcellular
      locolization].
AB  - OBJECTIVE: To examine the effect of SH2A gene in cell signal transduction and its
      subcellular localization. METHODS: RT-PCR method was used to amplify the coding
      sequence of SH2A gene. Eukaryotic recombined expression vector pcDNA 3.1-SH2A was
      constructed, and then Bel7402 cell and COS7 cell transfected by liposome.
      Multiple kinase assay was performed to examine the activity of protein kinase
      (PKC), mitogen activated protein kinase (MAPK), tyrosine protein kinase (TPK) in
      the transfected cells. Meantime, pEGFP-SH2A vector was also constructed and the
      cells transfected with it were examined by fluorescent microscopy. RESULTS:
      Recombined expression vector pcDNA3.2-SH2A and pEGFP-SH2A contained the coding
      sequence of SH2A cDNA. In both cell lines expressing SH2A gene, the cytoplasm PKC
      activity decreased by 40% or so, but no apparent alteration was found in MAPK and
      TPK activity. SH2A gene was found localized in the cytoplasm of transfected cells
      under fluorescent microscope. CONCLUSION: SH2A gene may act as an inhibiting
      factor in PKC signal transduction, and it is localized in cytoplasm.

PMID- 14669219
TI  - [Polymorphism of interleukin-10 gene promoter and its association with
      susceptibility to chronic obstructive pulmonary disease in Chinese Han people].
AB  - OBJECTIVE: To investigate the polymorphism of interleukin-10 (IL-10) gene
      promoters in Chinese Han people, and to disclose whether such polymorphism is
      associated with susceptibility to chronic obstructive pulmonary disease (COPD).
      METHODS: After the process of extracting genomic DNA from blood of 94 health
      smokers and 88 COPD smokers by use of phenol-chloroform-isoamyl alcohol, three
      single nucleotide polymorphism (SNP) sites in IL-10 gene promoter marked as 
      1082G/A,-819C/T,-592C/A were determined by polymerase chain reaction/restriction
      fragment length polymorphism analysis. RESULTS: Eleven different promoter
      genotypes were detected from all of the 182 smokers, and AA*TT*AA, AA*TC*AC,
      AA*TC*AA genotypes accounted for about 80% of genotypes in the research subjects.
      Two previously unreported haplotypes of IL-10 gene promoter (ATC and ACA) were
      found in Chinese Han people by analyzing the promoter genotypes. -1082G/A and 
      592C/A SNP sites polymorphisms were not associated with susceptibility to COPD,
      whereas the genotypes of -819C/T SNP site were associated with susceptibility to
      COPD in Chinese Han people. In respect to the alleles frequencies of the three
      SNP sites respectively, the Chinese Hans were similar to Japanese, but different
      from whites. CONCLUSION: Polymorphism of IL-10 -819C/T SNP site is associated
      with susceptibility to COPD in Chinese Han people; at least five haplotypes of IL
      10 gene promoter (ATA, ACC, GCC, ATC and ACA) exist in Chinese Han people.

PMID- 14669220
TI  - [Relationship of interleukin-1B and interleukin-1 receptor antagonist gene
      polymorphisms with chronic hepatitis B].
AB  - OBJECTIVE: To investigate the polymorphisms of interleukin-1B (IL-1B) promoter
      region -511C/T and interleukin-1 receptor antagonist (RN) gene, the relationship
      between the genotype of IL-1B and IL-1RN, and the susceptibility to chronic
      hepatitis B in Chinese population. METHODS: Genomic DNA was extracted from the
      peripheral blood of 190 patients with chronic hepatitis B and 249 normal controls
      and then was subjected to PCR amplification. The PCR product was digested by
      restriction endonuclease Ava I. The product of digestion was subjected to 2% gel
      electrophoresis and ethidium bromide staining. RESULTS: The IL-1B -511C allele
      was detected in 0.50 of normal controls and 0.48 of patients, while the IL-1B 
      511T allele was detected in 0.50 of normal controls and 0.52 of patients. The
      frequency of CC genotype was 0.26 (65/249) and in normal controls 0.24 (45/190)
      in patients. The frequency of CT genotype was 0.47 (118/249) in normal controls
      and 0.49 (94/190) in patients. The frequency of TT genotype was 0.27 (66/249) in
      normal controls and 0.27 (51/190) in patients. The HBV-DNA copies in chronic
      hepatitis B with CC genotype were significantly decreased, compared with controls
      (P<0.05). Only four (1/1, 1/2, 2/2 and 1/4) of the five kinds of polymorphism of
      IL-1RN were found in this study. The frequencies of 1/1, 1/2, 2/2 and 1/4 were
      0.88, 0.09, 0.01 and 0.02 in chronic hepatitis B patients respectively, while in
      controls were 0.81, 0.16, 0.01 and 0.02. The IL-1 RN*1 allele was detected in
      0.94 of chronic hepatitis B patients and in 0.90 of controls, while the IL-1RN*2
      allele was detected in 0.05 of patients and in 0.09 of normal controls. The
      frequencies of 1/2 genotype and IL-1RN*2 allele were lower in chronic hepatitis B
      than in controls (P<0.05). CONCLUSION: The polymorphisms of the promoter region 
      511C/T of IL-1B gene and IL-1RN intron 2 gene are associated with the development
      of chronic hepatitis B. The people with IL-1RN*2 allele may be protected against
      HBV infection, and the IL-1B -511 CC genotype may be linked to HBV-DNA copy.

PMID- 14669221
TI  - [Preliminary study on single nucleotide polymorphisms and linkage disequilibrium
      in promoter region of fibrinogen B beta gene].
AB  - OBJECTIVE: To investigate the distribution characters and linkage disequilibrium
      of single nucleotide polymorphisms (SNPs) -148C/T, -455G/A and -854G/A in the
      promoter region of fibrinogen B(FGB) beta gene. METHODS: Genotype and allele
      frequencies of FGB beta gene were examined by polymerase chain reaction
      restriction fragment length polymorphism and nucleotide sequencing methods in 377
      Chinese southern Han individuals. Three FGB beta SNPs Hardy-Weinberg equilibrium
      and linkage disequilibrium were analyzed with population genetics methods.
      RESULTS: The allele frequencies of 3 SNPs are in good agreement with Hardy
      Weinberg equilibrium. A total of 9 genotypes among the 377 individuals were
      identified in 3 SNPs. The genotype frequencies of -148CC, CT and TT were 0.597,
      0.358 and 0.045, respectively; the -455G/A genotype frequencies were the same as
      that of -148C/T SNP; the genotype frequencies of -854GG,GA, AA were
      0.820,0.178,0.002, respectively. The frequencies of rare allele -148T, -455A and 
      854A were 0.224,0.224 and 0.092, respectively, while the common allele
      frequencies were 0.776 for -148C, 0.776 for -455G, and 0.908 for -854G. There
      were no statistically significant differences in genotype and allele frequencies
      between the male and female groups (P>0.05). The relationship between -455G and 
      148C was completely concordant, but there was a random distribution between -854
      and -148 (-445) SNPs. CONCLUSION: The results show there is a complete linkage
      disequilibrium between -148C/T and -455G/A and a negative linkage disequilibrium
      between -854G/A and -148C/T, as well as between -854G/A and -455G/A. This study
      has provided population genetics data on FGB beta gene promoter in Chinese
      southern Han population.

PMID- 14669222
TI  - [Large deletion in mismatch repair genes uncovered by quantitative multiplex PCR
      high performance liquid chromatography system].
AB  - OBJECTIVE: Establishing a new method on the basis of multiplex PCR-high
      performance liquid chromatography (HPLC) for screening a large deletion in
      mismatch repair genes. METHODS: Thirty-five pairs of primers were used to amplify
      all 16 exons of MSH2 and all 19 exons of MLH1 gene in 8 multiplex PCR. The
      products of multiplex PCR were analysed for the large deletion with Double Strand
      DNA Analysis System of HPLC. Firstly, validation of the method was tested on
      positive and negative controls in blind analysis. Secondly, 14 blood cell DNA
      samples from hereditary nonpolyposis colorectal cancer (HNPCC) patients and 13
      colorectal cancer (CRC) tissues DNA samples from sporadic CRC patients were
      checked with the new developed method. RESULTS: (1) the genomic deletions in all
      4 of positive controls were identically uncovered with the new method; (2) a
      novel germline and a novel somatic large deletions were unveiled in 1/14 HNPCC
      patients and in 1/13 CRC tissues. CONCLUSION: The method developed on multiplex
      PCR-HPLC is reliable for uncovering large genomic deletion in mismatch repair
      genes, and can be taken as a valuable addition to mutation screening system.

PMID- 14669223
TI  - [Establishment of transgenic mice for HRX-EEN fusion gene].
AB  - OBJECTIVE: To study the biological function of fusion gene HRX-EEN and its role
      in leukemogenesis, and to provide an ideal animal model for anti-leukemia drug
      screening. METHODS: HRX-EEN fusion gene was constructed by use of three different
      DNA fragments, and it was inserted into hCG transgenic vector. G(0) transgenic
      mice were obtained by microinjection of the recombined DNA into the pronucleus of
      zygotes, followed by implantation of the injected zygotes into pseudopregnant
      mice. The integration of the transgene was tested by PCR and its expression by
      reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The sequence
      of recombined HRX-EEN gene was confirmed by sequencing. PCR testing revealed a
      total of 7 G(0) transgenic mice, these mice were then mated with C57 wild type
      mice. Except mouse No. 35 that died, the others all had their F1 offsprings. From
      these 6 lines of transgenic mice, HRX-EEN gene was found to be stably expressed
      in 3 lines by RT-PCR. Up to now, all transgenic mice expressing the fusion gene
      have no obvious abnormal phenotypes. CONCLUSION: A transgenic mice model in which
      the HRX-EEN fusion gene can be stably expressed has been established.

PMID- 14669224
TI  - [Clinical and experimental study of 38 cases with trisomy 8].
AB  - OBJECTIVE: To study the role of trisomy 8 in pathogenesis and progression of
      hematologic disease with trisomy 8. METHODS: The clinical data on 38 cases with
      trisomy 8 were investigated retrospectively. Fluorescence in situ hybridization
      (FISH) using Spectrum Orange labeled chromosome 8 centromere specific probe was
      carried out to detect trisomy 8 in 10 cases. RESULTS: Thirty-two of 38(84.2%)
      cases with trisomy 8, and fourteen of 17(82.4%) cases with trisomy 8 as the sole
      chromosome aberration were myeloid disorders such as myelodysplastic syndrome
      (MDS), acute myelocytic leukemia (AML), chronic myelocytic leukemia (CML). The
      incidence of trisomy 8 was higher in myeloid disease than in lymphocytic disease
      (5% vs 1.3%); the incidence of trisomy 8 was higher in acute monocytic leukemia
      than in other AML (6.1% vs 2.4%), and the incidence of trisomy 8 in chronic
      myelomonocytic leukemia( CMML) was higher than that in other myelodysplastic
      syndrome (MDS) (25% vs 13.2%); 17 cases had trisomy 8 as the sole chromosome
      aberration, 21 cases had other additional chromosome aberrations. The chromosome
      aberration was confirmed by FISH in 10 cases with trisomy 8 as the sole
      chromosome aberration. Eleven cases were treated with chemotherapy, among them
      only 10 cases data were available. Seven cases acquired complete remission but 3
      of them were M3, the other 3 cases had no response after two courses of
      chemotherapy. CONCLUSION: Trisomy 8 may play an important role in the
      pathogenesis and progression of the hematological disease, especially myeloid
      disease. Trisomy 8 might be related with differentiation abnormality of monocyte.

PMID- 14669225
TI  - [The effect of basic fibroblast growth factor in ovarian cancer growth and
      angiogenesis].
AB  - OBJECTIVE: To investigate whether basic fibroblast growth factor (bFGF) can
      induce the proliferation, invasion and angiogenesis of ovarian cancer or not.
      METHODS: Human ovarian cancer cell lines SKOV(3) 1 x 10(4)/ml were plated in 24
      well dishes, bFGF at 5, 10,15 and 20 ng/ml was added and crystal violet staining
      was given daily for 8 days, cell numbers were counted by determining OD490.
      SKOV(3) cells were plated in the center of 50% extra cellular matrix gel, bFGF at
      5 and 10 ng/ml was added and the migration distance of cells was measured daily.
      SKOV(3) 5 x 10(7)/ml were transplanted to BALB/c nude mice subcutaneous. One week
      later, bFGF, bFGF-MAb or 0.9% nature sodium was injected subcutaneously
      surrounding the tumor twice a week. Eight weeks later, the experiment ended and
      the volume of the tumors were measured. Intratumoral microvessel density (MVD)
      was measured by immunohistochemistry staining for factor VIII. RESULTS: bFGF at 0
      10 ng/ml could stimulate the proliferation of SKOV(3) concentration dependently
      (P<0.05). On the fifth day, the cell proliferation in 10 ng/ml group was 121%
      above control. bFGF could stimulate the invasion of SKOV(3) concentration
      dependently (P<0.05). On the seventh day, the migration distance in 5 ng/ml group
      was 1.16 cm and 153% above control, and that in 10 ng/ml group was 1.86 cm and
      245% above control. The average volume of transplanted tumors and MVD in bFGF
      group were 180% and 146% above control respectively those in bFGF-MAb group were
      63.7% and 62.8% above control respectively. CONCLUSION: bFGF can stimulate
      proliferation, invasion and angiogenesis of ovarian cancer markedly; bFGF-MAb can
      inhibit the angiogenesis and growth of ovarian cancer.

PMID- 14669226
TI  - [Study on exons 3 and 4 of alpha-synuclein gene in Chinese familial Parkinson
      disease patients].
AB  - OBJECTIVE: To study the relationship of Chinese familial Parkinson disease with
      alpha-synuclein gene. METHODS: Polymerase chain reaction-single strand
      conformational polymorphism (PCR-SSCP) and polymerase chain reaction-heteroduplex
      analysis(PCR-HA) were employed to detect the abnormal mobilization in the
      familial Parkinson disease and sporadic Parkinson disease patients, then it was
      verified by gene sequencing. RESULTS: No mutation was found in alpha-synuclein
      gene exons 3 and 4 by PCR-SSCP together with PCR-HA. An inserted c and an
      inserted t were found in intron 4, position 23 and position 67 respectively.
      CONCLUSION: (1) Exons 3 and 4 of alpha-synuclein gene are not the mutational hot
      spots of Chinese familial Parkinson disease. (2) Two polymorphisms were found in
      intron 4 of alpha-synuclein gene. They are 23 ins c and 67 ins t.

PMID- 14669227
TI  - [Study on lipoprotein lipase gene Hind III polymorphism in Chinese type IIb
      hyperlipoproteinemia].
AB  - OBJECTIVE: To investigate whether lipoprotein lipase (LPL) gene Hind III
      polymorphism is associated with Chinese type IIb hyperlipoproteinemia. METHODS:
      Lipoprotein lipase gene Hind III polymorphism was studied using polymerase chain
      reaction (PCR) and restriction fragment length polymorphisms (RFLP) in 103 type
      IIb hyperlipoproteinemia patients and 129 healthy subjects from a population of
      Chinese Hans in Chengdu area. RESULTS: Both in type IIb hyperlipoproteinemia
      group and control group, the H+H+ homozygote was the major allelotype. The H+
      allelic frequency of type IIb hyperlipoproteinemia group was higher than that of
      control group (0.864 vs 0.705, P<0.01). But the H- allelic frequency of type IIb
      hyperlipoproteinemia group was significantly lower than that of control group
      (0.136 vs 0.295, P<0.01). The plasma triglycerides (TG) level of H+H+ genotype
      was significantly higher than that of H+H- and H-H- genotypes (P<0.05 and
      P<0.01); the plasma TC level and TG/HDL C ratio were higher than those of H+H-
      and H-H- genotypes (P<0.05); apoA II levels of H+H+ and H+H- genotypes were
      significantly lower than that of H-H- genotype (P<0.01 and P<0.05). CONCLUSION:
      The Hind III RFLP at intron 8 of LPL gene is associated with type II b
      hyperlipoproteinemia to some extent in Chinese population.

PMID- 14669228
TI  - [Study on association between CC16 gene G38A mutation and asthma in the patients
      of Han population in Chongqing, China].
AB  - OBJECTIVE: To investigate the possible association between polymorphism of CC16
      gene exon 1 and asthma, the genotype and allele frequencies of CC16 gene exon 1
      in the asthmatic patients of Han population in southwest China were analyzed.
      METHODS: The authors determined the genotypes of CC16 gene exon 1 with polymerase
      chain reaction technique and restricted enzyme analysis, and then compared the
      genotype and allele frequencies of the gene of the asthmatic group with those of
      the healthy control group. RESULTS: There was no significant difference in
      genotype and allele frequencies of CC16 gene between the asthmatic group and
      control group. There was no association between the genotype and allele
      frequencies of gene and the severity of asthma. CONCLUSION: CC16 gene may be not
      a susceptibility gene of asthmatic patients of Han population in southwest China.

PMID- 14669229
TI  - [The NAD(P)H: quinone oxidoreductase 1 C609T polymorphism and susceptibility to
      esophageal cancer].
AB  - OBJECTIVE: To investigate the association of the NAD(P)H: quinone oxidoreductase
      1 (NQO1) C609T polymorphism with susceptibility to esophageal squamous cell
      carcinoma (ESCC) in a northern Chinese population. METHODS: The NQO1 C609T
      genotypes were determined by polymerase chain reaction-restriction fragment
      length polymorphisms (PCR-RFLP) analysis in 193 patients with ESCC and 141
      unrelated healthy controls. RESULTS: The frequency of the T allele (null) among
      ESCC patients was significantly higher than that among healthy controls (Chi
      square=4.86, P=0.028). The NQO1 C/C and C/T genotype distribution among ESCC
      patients was not significantly different from that among healthy controls (Chi
      square= 2.27 and 0.127; P=0.132 and 0.721, respectively). However, the T/T
      genotype frequency among ESCC patients was significantly higher than that among
      healthy controls (Chi-square=4.39, P=0.036). The NQO1 T/T genotype significantly
      increased the risk for developing ESCC, compared to the combination of C/C and
      C/T genotypes, with the adjusted odds ratio (OR) of 1.81 (95%CI: 1.04-3.15). This
      increased susceptibility exhibited pronouncedly in patients with family history
      of upper gastrointestinal cancers (adjusted OR=2.22, 95%CI 1.18-4.17).
      CONCLUSION: Determination of the NQO1 C609T genotype may be used as a
      stratification marker to predicate high-risk individuals for ESCC.

PMID- 14669230
TI  - [The relationship between IL-13 gene polymorphism and the levels of serum IL-13
      and serum eosinophil cation protein in asthmatic children].
AB  - OBJECTIVE: To explore the relationship between IL-3 gene polymorphism and the
      levels of serum IL-3 and eosinophil cation protein (ECP) for understanding the
      role of IL-3 gene polymorphism in the mechanism of childhood asthma. METHODS: The
      method of restriction fragment length polymorphism (RFLP) was adopted in
      detecting +1923 site polymorphism of IL-13 gene in intron 3 region, ELISA was
      employed in detecting the level of serum IL-13, and fluorescent enzyme-linked
      immunoassay was used to detect the level of serum ECP. RESULTS: The frequency
      distribution of TT, TC genotypes of IL-13 Intron 3+1923 site in asthmatic
      children was higher than that of CC genotype in normal control (P<0.05), and the
      levels of serum IL-13 and ECP of TT, TC genotypes were significantly higher than
      those of CC genotype respectively (P<0.01). CONCLUSION: The close relationship of
      IL-3 gene polymorphism with the levels of serum IL-13 and ECP suggests that IL-3
      gene polymorphism may play an important role in the mechanism of childhood
      asthma.

PMID- 14669231
TI  - Hominid cranial remains from upper Pleistocene deposits at Aduma, Middle Awash,
      Ethiopia.
AB  - The Upper Pleistocene localities of Aduma and Bouri have yielded hominid fossils
      and extensive Middle Stone Age (MSA) archaeological assemblages. The vertebrate
      fossils recovered include parts of four hominid crania from Aduma and a complete
      right parietal from Bouri. Archaeological associations and radiometric techniques
      suggest an Upper Pleistocene age for these hominids. The more complete cranium
      from Aduma (ADU-VP-1/3) comprises most of the parietals, the occipital, and part
      of the frontal. This cranium is compared to late Middle and Upper Pleistocene
      hominid crania from Africa and the Middle East. The Aduma cranium shows a mosaic
      of cranial features shared with "premodern" and anatomically modern Homo sapiens.
      However, the posterior and lateral cranial dimensions, and most of its anatomy,
      are centered among modern humans and resemble specimens from Omo, Skhul, and
      Qafzeh. As a result, the Aduma and Bouri Upper Pleistocene hominids are assigned
      to anatomically modern Homo sapiens.

PMID- 14669232
TI  - Systematics and evolution of the Jacchus group of marmosets (Platyrrhini).
AB  - Interspecific differentiation and geographic variation patterns in 39 skull
      traits of eastern Brazilian marmosets are analyzed. Eastern Callithrix taxa are
      distinct morphologically, and no evidence of intergradation among taxa is
      observed. Instead, there are sharp, stepped morphological boundaries among taxa,
      consistent with species-level distinction. The morphological similarity cluster
      diagram obtained from Mahalanobis distances is different from available molecular
      trees, and the general picture emerging is that the eastern Callithrix taxa
      should be considered as good species arising recently in South American history.
      In particular, C. kuhlii is morphologically distinct from other marmoset taxa,
      including C. geoffroyi and C. penicillata, which were previously hypothesized to
      be the parental populations that formed C. kuhlii by hybridization. Furthermore,
      C. kuhlii populations from southeastern Bahia do not overlap morphologically with
      any C. penicillata population, including the upper Sao Francisco River
      populations that display skin colors and pelage patterns to some extent similar
      to true Kuhli's marmosets. There is a negative, though insignificant, correlation
      between the morphological distance matrix and a Mahalanobis distance matrix
      estimated from nine climatic variables, a pattern opposite to that expected under
      a parapatric speciation model. This result, together with the lack of clinal
      variation in skull traits, suggests that an allopatric model of speciation might
      best explain eastern marmoset diversification.

PMID- 14669233
TI  - An ill child among mid-Holocene foragers of Southern Africa.
AB  - The skeletal remains of an infant from a southwest South African rock shelter at
      Byneskranskop show pervasive abnormalities that are consistent with the effects
      of hypertrophic (hyperplastic) rickets. Diagnostic features include beading of
      the costochondral junctions of the ribs, flaring and tilting of the metaphyses,
      and cupping of the distal ulna, as well as general skeletal hypertrophy. With an
      uncalibrated accelerator mass spectrometry (AMS) radiocarbon date of 4820 +/- 90
      BP (TO-9531), this is a very early instance of the condition, among foragers
      whose environment and diet make dietary shortages of active vitamin D or dietary
      calcium improbable. Carbon and nitrogen stable isotope ratios indicate a mixed
      diet, including marine as well as terrestrial protein. Solicitous care maintained
      the sick infant to an estimated age of 3.5-5 months; it was buried in a manner
      like that of other deceased group members. This case suggests that if infanticide
      was practiced, it was an option only during the immediate perinatal period, when
      this infant would have appeared normal. This is consistent with documentation of
      infanticide practices among historic foragers from southern Africa.

PMID- 14669234
TI  - Bone protects proteins over thousands of years: extraction, analysis, and
      interpretation of extracellular matrix proteins in archeological skeletal
      remains.
AB  - In a good state of preservation, bone conserves the entire protein pattern of
      extracellular bone matrix proteins over thousands of years. The quality of the
      profiles of matrix proteins isolated from ancient bones (ranging from the pre
      Pottery Neolithic Phase to Early Modern Times from different archaeological sites
      in different geographical areas), separated by electrophoresis, is as good as
      those from recent bones. Molecules arising from collagenous proteins (e.g.,
      collagen type I), from the noncollagenous group (e.g., osteonectin), and from the
      immune system (e.g., immunoglobulin G) were identified in Western blots by
      specific antibodies. A comparative study of the immunoglobulin G content of the
      bones of five prehistoric children showed the lowest immunoglobulin G content in
      a child who suffered from chronic scurvy. Ancient bone proteins were also
      separated by two-dimensional electrophoresis. This technique makes fractionation
      of the complex protein mixtures of extracellular bone matrix more reproducible.
      Bone retains a chemical memory of earlier metabolic stimuli in its configuration
      of collagenous and noncollagenous proteins. In combination with the results of
      the microscopic examination of ancient bone, it should be possible to obtain more
      reliable information on the history and the evolution of diseases, based on
      analysis of intact proteins.

PMID- 14669235
TI  - Social organization of the golden brown mouse lemur (Microcebus ravelobensis).
AB  - Our study provides the first data on the social organization of the golden brown
      mouse lemur, a nocturnal primate discovered in northwestern Madagascar in 1994.
      The study was carried out in two 6-month field periods during the dry season,
      covering time before and during the mating season. The spatial and temporal
      distributions of the sexes in the population were investigated by mark/recapture
      and radiotelemetry. Focal observations and the determination of sleeping
      associations provided further insights into the sociality of this solitary
      forager. High intra- and intersexual home-range overlaps occurred throughout the
      study. In general, individuals of both sexes had spatial access to more than one
      conspecific of the same and the opposite sex. We found no indication for spatial
      monopolization of females by certain males. These results suggest a dispersed
      multimale/multifemale system with a promiscuous mating pattern. Individuals
      showed temporal stability in their home range locations and interacted regularly
      with conspecifics. Five sleeping groups were identified during the study period:
      one female group and four mixed-sex groups. Even though sleeping sites were
      changed frequently, sleeping-group compositions remained stable over time.
      Thermoregulatory constraints are the most likely explanation for sleeping-group
      composition with members of both sexes in this species. Mixed-sex sleeping groups
      can be described as the basic social unit within this dispersed
      multimale/multifemale society.

PMID- 14669236
TI  - Sex differences in play among western lowland gorilla (Gorilla gorilla gorilla)
      infants: implications for adult behavior and social structure.
AB  - Mammalian play is believed to improve motor skills as well as facilitate the
      development of social relationships. Given the marked sexual dimorphism in
      gorilla body size and the role assumed by the male in protecting the group from
      conspecifics and predators, the motor-training hypothesis of play predicts that
      male infants should exhibit higher frequencies of social play than female
      infants, and that males should prefer to play with other males. Given that adult
      female gorillas are strongly attracted to adult breeding males and form only weak
      social bonds with unrelated adult females, the social-relationship hypothesis of
      play predicts that female infants should prefer to play with males. These
      hypotheses were tested in a 22-month study of 12 gorilla infants, aged between 0
      5 years, living in three zoological parks in Chicago and Atlanta. Consistent with
      the hypotheses, male infants played more than female infants did, and both male
      and female infants preferred to play with males rather than with females. These
      findings suggest that sex differences in play in the great apes and other
      primates can be predicted by the characteristics of adult behavior and social
      structure above and beyond the patterns of sex-biased dispersal or coalition
      formation with same-sex kin.

PMID- 14669237
TI  - Sex difference in chimpanzee handedness.
AB  - Chimpanzees at Mahale, Tanzania, show strong individual hand preferences when
      they use bimanual actions in processing the fruit of Saba florida and Citrus
      lemon. The direction of hand preference differs between the sexes: most males are
      left-handed, whereas most females are right-handed. Monkeys and apes are
      considered to lack "handedness," in the sense of a population mode of left- or
      right-hand preference; they are normally ambidextrous. Indeed, strong individual
      preferences were previously seldom found in natural tasks. We propose that
      lateralization of manual actions becomes advantageous in bimanual tasks, which
      involve role differentiation between the hands and a need to combine power and
      precision. If the pattern of lateralization found here reflects the ancestral
      state, common to chimpanzees and humans, this may explain why, in modern humans,
      women tend more strongly to be right-handed than men, who include a larger
      minority of left-handers.

PMID- 14669238
TI  - Patterns of phenotypic covariation and correlation in modern humans as viewed
      from morphological integration.
AB  - Proportionality of phenotypic and genetic distance is of crucial importance to
      adequately focus on population history and structure, and it depends on the
      proportionality of genetic and phenotypic covariance. Constancy of phenotypic
      covariances is unlikely without constancy of genetic covariation if the latter is
      a substantial component of the former. If phenotypic patterns are found to be
      relatively stable, the most probable explanation is that genetic covariance
      matrices are also stable. Factors like morphological integration account for such
      stability. Morphological integration can be studied by analyzing the
      relationships among morphological traits. We present here a comparison of
      phenotypic correlation and covariance structure among worldwide human
      populations. Correlation and covariance matrices between 47 cranial traits were
      obtained for 28 populations, and compared with design matrices representing
      functional and developmental constraints. Among-population differences in
      patterns of correlation and covariation were tested for association with matrices
      of genetic distances (obtained after an examination of 10 Alu-insertions) and
      with Mahalanobis distances (computed after craniometrical traits). All matrix
      correlations were estimated by means of Mantel tests. Results indicate that
      correlation and covariance structure in our species is stable, and that among
      group correlation/covariance similarity is not related to genetic or phenotypic
      distance. Conversely, genetic and morphological distance matrices were highly
      correlated. Correlation and covariation patterns were largely associated with
      functional and developmental factors, which probably account for the stability of
      covariance patterns.

PMID- 14669239
TI  - Ossification and midline shape changes of the human fetal cranial base.
AB  - An appreciation of ontogenetic changes to the cranial base is important for
      understanding the evolution of modern human skull form. Using geometric
      morphometric techniques, this study explores midline shape variations of the
      basicranium and midface during human prenatal ontogeny. In particular, the
      analysis sets out to explore shape variations associated with endochondral
      ossification and to reassess shape variations previously observed on the basis of
      angular measures.Fifty-four formalin-preserved human fetuses were imaged using
      high-resolution MRI. Coordinates for 10 landmarks defining the midline
      basicranium and midface were acquired and areas of ossification in the midline
      basioccipital, basisphenoid, and presphenoid cartilages were measured as
      percentages of overall cranial base area. The results show shape variations with
      increasing fetal size that are consistent with cranial base retroflexion,
      anterior facial projection and dorsal facial rotation. These growth variations
      are centered on the midsphenoid area and are associated with disproportionate
      variations of sphenoid height and length. Small but significant correlations were
      observed between ossification of the presphenoid cartilage and components of
      shape that described, among other variations, sphenoid shortening. While
      ossification cannot be directly linked with the shape variations observed, it
      seems likely that bone formation plays a role in modulating the influence of
      other factors on the fetal cranial base.

PMID- 14669240
TI  - Secular change in body height and cephalic index of Croatian medical students
      (University of Rijeka).
AB  - An investigation of body height and cephalic measurements was performed among
      five groups of first-year medical students of the University of Rijeka School of
      Medicine (Rijeka, Croatia). Body height and different cephalic measurements
      showed normal distribution, both in male and female students. Differences between
      measured variables were statistically analyzed by ANOVA. No significant
      difference with regard to year of birth was found in either males or females. The
      cephalic index showed no statistically significant difference between sexes or
      with regard to body height, while head breadth and length correlated
      significantly with birth year and body height, both in males and females. Head
      breadth decreased within the study period, while head length increased. Results
      were compared with those of similar studies from the mid-20th century. Student's
      t-test showed a significant change of cephalic indices and other head
      measurements, but not of body height, in males. The frequency difference between
      various head shapes was tested using the chi-square test. A significant increase
      of dolichocephalic and mesocephalic and a significant decrease of brachycephalic
      head shape were found in both sexes. These results suggest a continuity of the
      debrachycephalization process observed in our population at the past midcentury.

PMID- 14669243
TI  - Antidiabetic herbal drugs officially approved in China.
AB  - Over the centuries, Chinese herbal drugs have served as a major source of
      medicines for the prevention and treatment of diseases including diabetes
      mellitus (known as 'Xiao-ke'). It is estimated that more than 200 species of
      plants exhibit hypoglycaemic properties, including many common plants, such as
      pumpkin, wheat, celery, wax guard, lotus root and bitter melon. To date, hundreds
      of herbs and traditional Chinese medicine formulas have been reported to have
      been used for the treatment of diabetes mellitus. This paper provides a brief
      review of the antidiabetic drugs of plant origin that have been approved by the
      Chinese health regulatory agency for commercial use in China. It was believed,
      through pharmacological studies, that medicinal herbs were meticulously organized
      in these antidiabetic drug formulas such that polysaccharide containing herbs
      restore the functions of pancreatic tissues and cause an increase in insulin
      output by the functional beta cells, while other ingredients enhance the
      microcirculation, increase the availability of insulin and facilitate the
      metabolism in insulin-dependent processes. Pharmacological and clinical
      evaluations indicated that these drugs had a mild, but significant, blood glucose
      lowering effect and that the long-term use of these agents may be advantageous
      over chemical drugs in alleviating some of the chronic diseases and complications
      caused by diabetes. Additionally, the use of these natural agents in conjunction
      with conventional drug treatments, such as a chemical agent or insulin, permits
      the use of lower doses of the drug and/or decreased frequency of administration
      which decreases the side effects most commonly observed.

PMID- 14669244
TI  - Possible mechanisms of action of the neutral extract from Bidens pilosa L. leaves
      on the cardiovascular system of anaesthetized rats.
AB  - The aim of this study was to investigate the hypotensive and cardiac effects of
      the neutral extract from Bidens pilosa leaves. Intravenous administration of the
      extract resulted in a biphasic dose-related hypotensive activity. In normotensive
      rats (NTR), B. pilosa decreased systolic blood pressure by 18.26%, 42.5% and 30%
      at doses of 10, 20 and 30 mg/kg, respectively. In spontaneously hypertensive rats
      (SHR), the decrease in systolic blood pressure was 25.77%, 38.96% and 28.64% at
      the above doses, respectively. These doses induced hypotension by 27%, 34.13% and
      18.73% respectively in salt-loaded hypertensive rats. In NTR, B. pilosa reduced
      heart rate by 23.68% and 61.18% at doses of 20 and 30 mg/kg, respectively. The
      force of contraction of the heart was only affected at 30 mg/kg. The initial
      phase of hypotensive response was partially inhibited by atropine while
      propranolol increased this effect. These results suggest that B. pilosa exhibited
      its fi rst hypotensive effects by acting on the cardiac pump efficiency and
      secondly through vasodilation.

PMID- 14669245
TI  - Immunopotentiating properties of Cryptolepis buchanani root extract.
AB  - The ethanol extract (95%) of the root of the plant Cryptolepis buchanani (EECB)
      was investigated for immunomodulatory activity in mice and rats. The oral
      administration of EECB caused significant stimulation of the delayed type
      hypersensitivity (DTH) reaction and humoral antibody production. The oral LD50
      was found to be more than 3 g/kg in both rats and mice.

PMID- 14669246
TI  - Relaxant effects of different fractions of essential oil from Carum copticum on
      guinea pig tracheal chains.
AB  - In previous studies, the relaxant and anticholinergic (functional antagonism),
      histamine(H1) inhibitory, and xanthine-like activity effect of Carum copticum
      have been demonstrated on guinea pig tracheal chains. To investigate the
      effective component(s) of this plant, responsible for the observed
      bronchodilatory effect, fractionation of the essential oil from Carum copticum
      was carried out and the relaxant effects of different fractions were examined in
      this study. The bronchodilatory effect of different fractions of essential oil
      from Carum copticum and theophylline in comparison with ethanol was examined by
      their relaxant effects on precontracted tracheal chains of guinea pig by 60 mM
      KCl (group 1) and 10 microM methacholine in two different conditions including:
      non-incubated tissues (group 2) and incubated tissues with 1 microM propranolol
      and 1 microM chlorpheniramine (group 3). In addition the relaxant effect of
      carvacrol was also examined on precontracted tracheal chains of guinea pig by 10
      microM methacholine (group 4), (for each group, n = 5). In group 1 experiments,
      only theophylline and fraction 2 showed significant relaxant effect compared to
      that of ethanol. Fraction 2 and 3 of essential oil from carum copticum showed
      potent and volume (concentration) dependent relaxant effects comparable to that
      of theophylline in groups 2 and 3 experiments. The relaxant effects of different
      volumes of these two fractions were significantly higher than that of ethanol (p
      < 0.05 to p < 0.002 ). The volumes of fraction 1 showed relatively small relaxant
      effects in groups 2 and 3 experiments which were not significantly different from
      that of ethanol. However, the relaxant effect of different volumes of fractions 2
      and 3 obtained in group 2 experiments were not significantly different from those
      of group 3 experiments. The volumes of fraction 4 did not show any relaxant
      effects. In addition volumes of carvacrol also showed comparable relaxant effect
      with those of fraction 2 and theophylline which was significantly greater than
      that of ethanol. These results indicate that the relaxant effect of essential oil
      from carum copticum is mainly due to its fraction 2 which is presumably carvacrol
      and to lesser extent due to fraction 3, and their relaxant effects are not due to
      anticholinergic or beta-adrenegic stimulatory effects.

PMID- 14669247
TI  - Radiomodulatory influence of Rajgira (Amaranthus paniculatus) leaf extract in
      Swiss albino mice.
AB  - Radiomodulatory effect of Rajgira leaf extract against 6, 8 and 10 Gy gamma
      radiation has been evaluated by 30 day survival of Swiss albino mice. Animals of
      control groups (untreated irradiated) showed diarrhoea, ruffled hairs, epilation,
      facial edema and consistent decrease in body weight. These signs were less
      severe/absent in experimental groups (Rajgira treated irradiated), and recovery
      in body weight was also early and faster. Thirty day survivability was 66 per
      cent in control group, exposed to 6 Gy, whereas no animal survived beyond 14 and
      10 days after irradiation with 8 and 10 Gy gamma rays respectively. However, 100,
      60 and 25 percent survivability was observed in experimental groups at 6, 8 and
      10 Gy respectively. Regression analysis of survival data showed that the LD50/30
      values were 6.33 and 8.62 Gy for control and experimental animals respectively.
      The dose reduction factor (DRF) was computed as 1.36. A significant decrease in
      GSH content and increase in LPO level was observed in control animals, whereas in
      Rajgira pretreated irradiated animals the level of GSH was recorded significantly
      higher but LPO level decreased significantly. The results from the present study
      suggest that Rajgira pretreatment provide protection against gamma irradiation in
      mice.

PMID- 14669248
TI  - Cytotoxicity and antimicrobial activity of goniothalamin isolated from Bryonopsis
      laciniosa.
AB  - The cytotoxicity and antimicrobial activity of goniothalamin isolated from
      Bryonopsis laciniosa was investigated. Goniothalamin showed potent cytotoxicity
      with LC50 values (5.03 microg/mL) comparable with the reference standard agent,
      gallic acid. It also showed weak antibacterial and significant antifungal
      activity against a wide range of gram positive and gram negative bacteria and
      fungi. The antibacterial (minimum inhibitory concentration) effect against
      Bacillus cereus and Shigella shiga was found to be 64 microg/mL.

PMID- 14669249
TI  - Antitumour potential of a polysaccharide-rich substance from the fruit juice of
      Morinda citrifolia (Noni) on sarcoma 180 ascites tumour in mice.
AB  - An immunomodulatory polysaccharide-rich substance (Noni-ppt) from the fruit juice
      of Morinda citrifolia has been found to possess both prophylactic and therapeutic
      potentials against the immunomodulator sensitive Sarcoma 180 tumour system. The
      antitumour activity of Noni-ppt produced a cure rate of 25%-45% in allogeneic
      mice and its activity was completely abolished by the concomitant administration
      of specific inhibitors of macrophages (2-chloroadenosine), T cells (cyclosporine)
      or natural killer (NK) cells (anti-asialo GM1 antibody). Noni-ppt showed
      synergistic or additive beneficial effects when combined with a broad spectrum of
      chemotherapeutic drugs, including cisplatin, adriamycin, mitomycin-C, bleomycin,
      etoposide, 5- fl uorouracil, vincristine or camptothecin. It was not beneficial
      when combined with paclitaxel, cytosine arabinoside, or immunosuppressive
      anticancer drugs such as cyclophosphamide, methotrexate or 6-thioguanine. Noni
      ppt also demonstrated beneficial effects when combined with the Th1 cytokine,
      interferon gamma, but its activity was abolished when combined with Th2
      cytokines, interleukin-4 or interleukin-10, thereby suggesting that Noni-ppt
      induces a Th1 dominant immune status in vivo. The combination of Noni-ppt with
      imexon, a synthetic immunomodulator, also demonstrated beneficial effects, but
      not when combined with the MVE-2 copolymer, a high molecular weight
      immunomodulator. It was also not effective when combined with interleukin-2 or
      interleukin-12.

PMID- 14669250
TI  - Treatment of patients with arthrosis of hip or knee with an aqueous extract of
      devil's claw (Harpagophytum procumbens DC.).
AB  - Preparations made from the secondary tubers of Devil's claw (Harpagophytum
      procumbens) are successfully used in patients with rheumatic diseases (arthrosis
      and low back pain). In order to add data on the efficacy and long-term safety of
      an aqueous extract (Doloteffin; 2400 mg extract daily, corresponding to 50 mg
      harpagoside), which has been tested successfully in patients with low back pain,
      an uncontrolled multicentre drug surveillance study for about 12 weeks was
      conducted in 75 patients with arthrosis of the hip or knee. To standardize the
      assessment of treatment effects, the Western Ontario and McMaster Universities
      (WOMAC) osteoarthritis index (10 point scale) as well as the 10 cm VAS pain scale
      were used. The results of the study revealed a strong reduction of pain and the
      symptoms of osteoarthritis. There was a relevant improvement of each WOMAC
      subscale as well as of the total WOMAC index: 23.8% for the pain subscale, 22.2%
      for the stiffness subscale and 23.1% for the physical function subscale. The
      WOMAC total score was reduced by 22.9%. VAS pain scores were decreased by 25.8%
      for actual pain, 25.2% for average pain, 22.6% for worst pain and 24.5% for the
      total pain score. The physicians reported a continuous improvement in typical
      clinical findings such as 45.5% for pain on palpation, 35% for limitation of
      mobility and 25.4% for joint crepitus. Only two cases of possible adverse drug
      reactions were reported (dyspeptic complaints and a sensation of fullness).
      Although this was an open clinical study, the results suggest that this Devil's
      claw extract has a clinically beneficial effect in the treatment of arthrosis of
      the hip or knee.

PMID- 14669251
TI  - Anti-sickling potential of a Nigerian herbal formula (ajawaron HF) and the major
      plant component (Cissus populnea L. CPK).
AB  - The anti-sickling activities of the extracts of the roots of a plant Cissus
      populnea L. (CPK) (a major constituent of a herbal formula Ajawaron HF used in
      the management of sickle cell disease in south-west Nigeria) has been examined.
      Phytochemical examination of the extract showed the presence of anthraquinone
      derivatives, steroidal glycosides and cardiac glycosides. Alkaloids and tannins
      were completely absent in the CPK extracts. Evaluation of the anti-sickling
      activity involved the use of both positive (p-hydroxybenzoic acid, 5 microg/mL)
      and negative control (normal saline) for each set of experiments aimed at the
      inhibition of sodium metabisulphite-induced sickling of the HbSS red blood cells
      obtained from confirmed non-crisis state sickle-cell patients. The chloroform and
      water partitioned fractions of the cold methanol extracts of CPK exhibited a
      62.2% and 52.9% inhibition of sickling, respectively, at 180 min. The herbal
      formula (HF) aqueous extract showed the highest anti-sickling activity on a
      weight by weight basis of all the extracts and fractions tested, giving a 71.4%
      inhibition of sickling at the end of 180 min incubation when compared with the
      normal saline control. The maximum percentage inhibition of sickling exhibited by
      the p-hydroxybenzoic acid control was 46.0% at 90 min incubation.

PMID- 14669252
TI  - Evaluation of the antimicrobial property of Polyalthia longifolia var. pendula:
      isolation of a lactone as the active antibacterial agent from the ethanol extract
      of the stem.
AB  - Bioassay guided fractionation of the ethanolic extract of Polyalthia longifolia
      var. pendula stem, which showed promising antibacterial activity against thirteen
      Gram-positive and nine Gram-negative organisms, furnished (3S,4R)-3,4,5
      trihydroxypentanoic acid-1,4-lactone (1) as the active principle. The structure
      of (1) was established by UV, IR, mass, 1H and 13C NMR as well as 2D NMR spectral
      studies and the formation of its acetate (1a). On acetylation activity of (1) was
      markedly reduced. It is synthetically well known and only recently isolated from
      two plants, however, its antimicrobial activity was not reported earlier. The
      extract, fractions and pure compounds did not show any remarkable activity
      against fungi and Mycobacterium fortuitum, and M. smegmatis.

PMID- 14669253
TI  - Mangifera indica L. extract (Vimang) and mangiferin modulate mouse humoral immune
      responses.
AB  - The present study investigated the effects of orally administered Vimang (an
      aqueous extract of Mangifera indica) and mangiferin (the major polyphenol present
      in Vimang) on mouse antibody responses induced by inoculation with spores of
      microsporidian parasites. Inoculation induced specific antibody production with
      an exponential timecourse, peaking after about one month. Vimang significantly
      inhibited this antibody production from about three weeks post-inoculation, and
      most markedly by four weeks post-inoculation; by contrast, mangiferin had no
      significant effect. Determination of Ig isotypes showed that the IgM to IgG
      switch began about four weeks post-inoculation, with IgG2a predominating. Vimang
      significantly inhibited IgG production, but had no effect on IgM. Mangiferin did
      no affect either IgM or IgG2a, but significantly enhanced production of IgG1 and
      IgG2b. Neither Vimang nor mangiferin enhanced specific antibody secretion by
      splenic plasma cells from mice inoculated with microsporidian spores, whether
      administered in vivo before serum extraction or in vitro to the culture medium.
      Inoculation with spores induced splenomegaly, which was significantly reduced by
      Vimang and significantly enhanced by mangiferin. These results suggest that
      components of Mangifera indica extracts may be of potential value for modulating
      the humoral response in different immunopathological disorders.

PMID- 14669254
TI  - Anti-obesity action of Salix matsudana leaves (Part 1). Anti-obesity action by
      polyphenols of Salix matsudana in high fat-diet treated rodent animals.
AB  - In preliminary experiments, polyphenol fractions prepared from the leaves of
      Salix matsudana reduced the elevation of the rat plasma triacylglycerol level at
      3 and 4 h after oral administration of a lipid emulsion containing corn oil, at a
      dose of 570 mg/kg. The present study examined the anti-obesity action of
      polyphenol fractions of S. matsudana leaves by testing whether the polyphenol
      fractions prevented the obesity induced by feeding a high-fat diet to female mice
      for 9 weeks. Body weights at 2-9 weeks and the fi nal parametrial adipose tissue
      weights were significantly lower in mice fed the high-fat diet with 5%
      polyphenols of S. matsudana leaves than in those fed the high-fat diet alone. The
      polyphenols of S. matsudana leaves also significantly reduced the hepatic total
      cholesterol content, which was elevated in mice fed the high-fat diet alone. In
      addition, the polyphenol fractions of S. matsudana leaves inhibited palmitic acid
      uptake into brush border membrane vesicles prepared from rat jejunum and alpha
      amylase activity, and their fractions enhanced norepinephrine-induced lipolysis
      in fat cells. In conclusion, it is suggested that the inhibitory effects of the
      flavonoid glycoside fraction of S. matsudana leaves on high-fat diet-induced
      obesity might be due to the inhibition of carbohydrate and lipid absorption from
      small intestine through the inhibition of alpha-amylase and palmitic acid uptake
      into small intestinal brush border membrane or by accelerating fat mobilization
      through enhancing norepinephrine-induced lipolysis in fat cells.

PMID- 14669255
TI  - Anti-obesity action of Salix matsudana leaves (Part 2). Isolation of anti-obesity
      effectors from polyphenol fractions of Salix matsudana.
AB  - Previously, it was reported that polyphenol fractions prepared from the leaves of
      Salix matsudana reduced the elevation of the rat plasma triacylglycerol level at
      3 and 4 h after oral administration of a lipid emulsion containing corn oil, at a
      dose of 570 mg/kg. Moreover, body weights at 2-9 weeks and the fi nal parametrial
      adipose tissue weights were significantly lower in mice fed the high-fat diet
      with 5% polyphenol fractions of S. matsudana leaves than in those fed the high
      fat diet alone. The polyphenol fractions of S. matsudana leaves also
      significantly reduced the hepatic total cholesterol content, which was elevated
      in mice fed the high-fat diet alone. In addition, the polyphenol fractions of S.
      matsudana leaves inhibited palmitic acid uptake into brush border membrane
      vesicles prepared from rat jejunum and alpha-amylase activity, and their
      fractions enhanced norepinephrine-induced lipolysis in fat cells. To clarify the
      active substances inhibiting the palmitic acid uptake into small intestinal brush
      border membrane, the alpha-amylase activity or enhancing the norepinephrine
      induced lipolyis in fat cells, the isolation of the active substances from
      polyphenol fraction was attempted using the above three assay systems. Compounds
      1, 2 and 3 were isolated from the polyphenol fractions and identified as apigenin
      7-O-d-glucoside, luteolin-7-O-d-glucoside and chrysoeriol-7-O-d-glucoside,
      respectively. Among three flavonoids, apigenin-7-O-d-glucoside inhibited alpha
      amylase activity, and luteolin-7-O-d-glucoside and chrysoeriol-7-O-d-glucoside
      inhibited palmitic acid uptake into small intestinal brush border membrane.
      Furthermore, three flavonoid glucosides enhanced norepinephrine-induced lipolysis
      in fat cells.

PMID- 14669256
TI  - Guarana (Paullinia cupana Mart.) offers protection against gastric lesions
      induced by ethanol and indomethacin in rats.
AB  - The effects of guarana (Paullinia cupana) extract were analyzed in rats on acute
      gastric lesions induced by ethanol and indomethacin and were compared to those
      produced by caffeine, a methylxanthine. Guarana (50 and 100 mg/kg p.o.)
      pretreated animals showed a significant reduction in the severity of gastric
      lesions induced by absolute ethanol in a manner similar to caffeine (20 and 30
      mg/kg p.o.). Against indomethacin-induced gastric ulceration, guarana at a higher
      dose offered significant protection but caffeine was ineffective at the doses
      tested. In 4 h pylorus-ligated rats, both guarana and caffeine caused significant
      diminution in the gastric secretory volume as well as the total acidity.
      Gastrointestinal transit in mice was not significantly affected by either of
      these agents. These findings indicate that guarana has a gastroprotective
      property that needs further elucidation as regards to its mechanism.

PMID- 14669257
TI  - Anthelminthic and antiallergic activities of Mangifera indica L. stem bark
      components Vimang and mangiferin.
AB  - This study investigated the antiallergic and anthelmintic properties of Vimang
      (an aqueous extract of Mangifera indica family stem bark) and mangiferin (the
      major polyphenol present in Vimang) administered orally to mice experimentally
      infected with the nematode, Trichinella spiralis. Treatment with Vimang or
      mangiferin (500 or 50 mg per kg body weight per day, respectively) throughout the
      parasite life cycle led to a significant decline in the number of parasite larvae
      encysted in the musculature; however, neither treatment was effective against
      adults in the gut. Treatment with Vimang or mangiferin likewise led to a
      significant decline in serum levels of specific anti-Trichinella IgE, throughout
      the parasite life cycle. Finally, oral treatment of rats with Vimang or
      mangiferin, daily for 50 days, inhibited mast cell degranulation as evaluated by
      the passive cutaneous anaphylaxis test (sensitization with infected mouse serum
      with a high IgE titre, then stimulation with the cytosolic fraction of T.
      spiralis muscle larvae). Since IgE plays a key role in the pathogenesis of
      allergic diseases, these results suggest that Vimang and mangiferin may be useful
      in the treatment of diseases of this type.

PMID- 14669259
TI  - Antifungal activity of wogonin.
AB  - The antifungal activity of the wogonin isolated from Holmskioldia sanguinea Retz
      was determined on four different fungal organisms. The pure compound wogonin
      significantly inhibited the growth of Aspergillus niger, Penicillium
      frequentance, P. notatum and Botrytis cinerea, in a concentration dependent
      fashion, when tested by turbidity and spore germination methods. The effects
      produced by the compound were compared with the standard antifungal agent
      griseofulvin.

PMID- 14669258
TI  - Effect of Nigella sativa (black seed) on subjective feeling in patients with
      allergic diseases.
AB  - Nigella sativa (black seed) is an important medicinal herb. In many Arabian,
      Asian and African countries, black seed oil is used as a natural remedy for a
      wide range of diseases, including various allergies. The plant's mechanism of
      action is still largely unknown. Due to the lack of study data on its efficacy in
      allergies, four studies on the clinical efficacy of Nigella sativa in allergic
      diseases are presented. In these studies, a total of 152 patients with allergic
      diseases (allergic rhinitis, bronchial asthma, atopic eczema) were treated with
      Nigella sativa oil, given in capsules at a dose of 40 to 80 mg/kg/day. The
      patients scored the subjective severity of target symptoms using a predefined
      scale. The following laboratory parameters were investigated: IgE, eosinophil
      count, endogenous cortisol in plasma and urine, ACTH, triglycerides, total
      cholesterol, LDL and HDL cholesterol and lymphocyte subpopulations. The score of
      subjective feeling decreased over the course of treatment with black seed oil in
      all four studies. A slight decrease in plasma triglycerides and a discrete
      increase in HDL cholesterol occurred while the lymphocyte subpopulations,
      endogenous cortisol levels and ACTH release remained unchanged. Black seed oil
      therefore proved to be an effective adjuvant for the treatment of allergic
      diseases.

PMID- 14669260
TI  - In vitro snake venom detoxifying action of some marine algae of Gulf of Mannar,
      south-east coast of India.
AB  - The extract of the brown seaweed Padina boergesenii and the red seaweed Hypnea
      valentiae was found to detoxify (in vitro) the venom of Naja nigricollis. There
      was a remarkable reduction in the mortality of albino mice after intraperitoneal
      (i.p.) administration of reconstituted venom with the extract compared to those
      challenged with the venom only. The survival of the animals exposed to the venom
      incubated with the different concentrations of the extract was used as the in
      vitro detoxification parameter.

PMID- 14669261
TI  - Antimalarial activity screening of some alkaloids and the plant extracts from
      Amaryllidaceae.
AB  - Four groups of Amaryllidaceae alkaloids, namely lycorine-, crinine-, tazettine-,
      and galanthamine-type, as well as plant extracts of the Amaryllidaceae plants
      (Pancratium maritimum, Leucojum aestivum, and Narcissus tazetta ssp. tazetta)
      growing in Turkey were evaluated in vitro for their ability to inhibit Plasmodium
      falciparum growth by a high-throughput screening method with a 96-well microtiter
      plate. All four groups of alkaloids exhibited antimalarial activity at different
      potencies. 6-Hydroxyhaemanthamine, haemanthamine and lycorine were found to be
      the most potent alkaloids against P. falciparum (T9.96) and galanthamine and
      tazettine had the least potent activity against P. falciparum (K1).

PMID- 14669262
TI  - Inhibitory effects of several flavonoids on E-selectin expression on human
      umbilical vein endothelial cells stimulated by tumor necrosis factor-alpha.
AB  - The present study investigates the suppressive effect of flavonoids on TNF-alpha
      stimulated E-selectin expression on HUVECs by carrying out a comparative
      examination of the 37 flavonoids. Several flavonoids: fisetin, luteolin and
      apigenin (subclass of flavone), kaempferol and quercetin (flavonols), eriodictyol
      (flavanones), genistein (isoflavones) and butein (chalcone) exhibit the
      inhibitory effects. Considerations to the structure of flavonoids, the C2-C3
      double bond of C-ring and 4-oxo functional group are essential for their
      inhibition activities. These results help to explain the pharmacological efficacy
      of flavonoids as anti-inflammatory compounds.

PMID- 14669263
TI  - Protonophoric and uncoupling activity of royleanones from Salvia officinalis and
      euvimals from Eucalyptus viminalis.
AB  - The mechanism of action of quinones from the roots of Salvia officinalis L.
      (royleanones) and terpenoid phenolaldehydes from the leaves of Eucalyptus
      viminalis Labill. (euvimals) was studied. Royleanones and euvimals displayed
      marked protonophoric activity on artificial bilayer lipid membranes in vitro, and
      exerted an uncoupling action on oxidative phosphorylation in isolated rat liver
      mitochondria. The results suggest that biological membranes are the primary
      targets of royleanones and euvimals, and the protonophoric activity may
      contribute to the cytotoxicity and antimicrobial properties of these compounds.

PMID- 14669264
TI  - Supplementation of fenugreek leaves to diabetic rats. Effect on carbohydrate
      metabolic enzymes in diabetic liver and kidney.
AB  - The present study was designed to evaluate the effect of supplementation of
      fenugreek leaves, an indigenous plant widely used in Indian Ayurvedic medicine
      for the treatment of diabetes mellitus, in streptozotocin induced diabetic rats.
      Supplementation of the diet with fenugreek leaves showed a significant effect on
      hyperglycaemia, hypoinsulinaemia and glycosylated haemoglobin in streptozotocin
      diabetic rats. Fenugreek leaves improved the body weight and liver glycogen.
      Fenugreek leaves also showed a significant effect on key carbohydrate metabolic
      enzymes in diabetic rats. The effect of fenugreek leaves was found to be similar
      to that of glibenclamide. Thus, fenugreek leaves exhibited antidiabetic action in
      streptozotocin-induced diabetic rats. Insulin restored all the parameters to near
      normal levels in diabetic rats.

PMID- 14669265
TI  - Combination effects of chloroquine with the febrifugine and isofebrifugine
      mixture against a blood-induced infection with chloroquine-resistant Plasmodium
      berghei NK65 in ICR mice.
AB  - The combination effects of chloroquine with a mixture of febrifugine and
      isofebrifugine were evaluated against a blood-induced infection with chloroquine
      resistant P. berghei NK65 in ICR mice. Mice in the untreated control showed a
      progressively increasing parasitemia leading to mouse death. A two-day dosage of
      20 mg base/kg of chloroquine alone showed little effect against P. berghei NK65
      infection, and all mice died from day 13 to 14 with an increasing parasitemia. A
      four-day dosage of 1 mg/kg of the febrifugine and isofebrifugine mixture alone
      showed a little antimalarial activity, but all mice died from day 19 to 27 with
      an increasing parasitemia. On the other hand, mice treated with chloroquine plus
      alkaloids survived during the experiment. All mice treated with chloroquine alone
      or the alkaloid mixture alone showed low parasitemia levels during a drug
      administration and following a few days, but then malaria parasites increased in
      the bloodstream of the treated mice until death. On the other hand, malaria
      parasites in the mice given chloroquine plus alkaloids decreased on day 6 and
      then were not detected by a microscopic examination during observation period.

PMID- 14669267
TI  - Leaders of progressions in wild mixed-species troops of saddleback (Saguinus
      fuscicollis) and mustached tamarins (S. mystax), with emphasis on color vision
      and sex.
AB  - Leadership of travel progression is an important aspect of group living. It is
      widely believed that trichromacy evolved to facilitate the detection and
      selection of fruit in the dappled light of a forest. Further, it has been
      proposed that in New World primate species, which typically contain a range of
      color vision phenotypes, at least one female in a group will be trichromatic
      (i.e., having three types of visual pigment, in contrast to the two types of
      pigment found in dichromatic individuals) and will lead the group to fruiting
      trees. We examine progression leadership within two wild mixed-species troops of
      saddleback (Saguinus fuscicollis) and mustached (Saguinus mystax) tamarins over a
      complete year. As whole units, the mixed-species troops were most frequently led
      by a mustached tamarin. This is the first time that mixed-species group
      leadership and individual leadership have been quantified in these tamarin
      species. In terms of single-species intragroup leadership, neither the visual
      status (dichromatic or trichromatic) nor the sex of individuals had a consistent
      effect across species. Saddleback tamarin groups were led by males more
      frequently than females, while evidence suggests that mustached tamarins may be
      female-led. The notion that all groups contain at least one trichromatic female
      that leads the troop to feeding trees was not supported.

PMID- 14669268
TI  - Throwing behavior and mass distribution of stone selection in tufted capuchin
      monkeys (Cebus apella).
AB  - Cannell [Journal of Archaeological Science 29:335-339, 2002] argued that sex
      based differences among humans in terms of the mass of chosen throwing stones
      could be used to infer body mass and patterns of sexual dimorphism in early
      hominids from Olduvai and Koobi Fora by examining the mass distributions of
      unaltered stone tools at those sites. We examined this hypothesis in tufted
      capuchin monkeys using a comparative approach, by investigating the relationships
      among body mass, sex, stone weight preference, and accuracy in a throwing task.
      The subject sample consisted of nine monkeys trained to perform an aimed-throwing
      task in which a food reward could be obtained by throwing a stone into a bucket.
      We found that 1) the subjects showed a strong mean stone mass preference; 2) the
      females chose heavier stones than the males, in terms of absolute mean selected
      stone mass and selected stone mass relative to body mass; 3) subjects threw more
      accurately when they used stones of preferred mass vs. stones of nonpreferred
      mass; and 4) overall, the males were more accurate in the throwing task than the
      females. We conclude that capuchins are highly selective when choosing throwing
      stones, and that this confers an advantage for throwing accuracy. Our results
      indicate that the sexually dimorphic pattern in stone mass preference observed
      among humans does not generalize to Cebus apella. We suggest that researchers
      examining this pattern in humans in an attempt to explain early hominid patterns
      of dimorphism and behavior should take into account not only stone weight
      preference, but also its adaptive advantage.

PMID- 14669269
TI  - Patterns of female dominance in Propithecus diadema edwardsi of Ranomafana
      National Park, Madagascar.
AB  - Many lemur species are characterized by some form of female dominance, ranging
      from female feeding priority to complete female dominance, although this is a
      rare trait in primates and other mammals. The status of the Milne-Edwards' sifaka
      (Propithecus diadema edwardsi), a diurnal lemur, is ambiguous. Some short-term
      studies have found little or no aggression. The aim of the current, long-term
      study was to quantify the intersexual-dominance patterns of this sifaka. The
      distribution, outcome, and context of aggressive interactions were studied in
      four groups of wild sifakas. The majority of intersexual aggressive interactions
      were decided, with the loser expressing submissive behavior. Intersexual
      aggressive interactions occurred in all social contexts, and within all social
      contexts the females won the vast majority (92.7-96.0%) of aggressive
      interactions. While aggression rates were low (0.22/hr), this evidence suggests
      female dominance. We propose that female dominance exists because it provides a
      fitness advantage to both males and females.

PMID- 14669270
TI  - Approach to a social stranger is associated with low central nervous system
      serotonergic responsivity in female cynomolgus monkeys (Macaca fascicularis).
AB  - It is widely hypothesized that individual differences in central nervous system
      (CNS) serotonergic activity underlie dimensional variation in "impulsive" vs.
      "inhibited" social behavior in both humans and nonhuman primates. To assess
      relative impulsivity in a social context, a behavioral challenge involving
      animals' exposure to a social stranger (termed the "Intruder Challenge") was
      recently validated in adolescent and adult male vervet monkeys (Cercopithecus
      aethiops sabaeus). Among these animals, monkeys that quickly approached the
      intruder were found to have lower cerebrospinal fluid (CSF) concentrations of the
      serotonin (5-HT) metabolite, 5-hydroxyindoleacetic acid, than less impulsive
      animals. In the present study we extended these observations to determine whether
      approach to a social stranger, as operationalized by the Intruder Challenge, is
      similarly associated with diminished CNS serotonergic function in female
      cynomolgus monkeys (Macaca fascicularis). Study animals were 25 adult monkeys
      that had been housed for 2 years in stable social groups. In each animal, the
      rise in plasma prolactin concentration induced by acute administration of the 5
      HT agonist, fenfluramine, was used to assess "net" central serotonergic
      responsivity. When exposed later to an unfamiliar female of the same species in a
      catch-cage placed for 20 min within the subjects' home enclosure, monkeys that
      approached to within 1 m of the intruder (median latency to approach=3 min) were
      found to have significantly smaller prolactin responses to fenfluramine
      (diminished serotonergic responsivity) compared to "inhibited" animals that
      failed to approach the intruder (t=2.9, df=23, P<0.009; rpb=-0.51). Neither
      approach behavior nor the animals' fenfluramine-induced prolactin responses
      covaried significantly with nondirected expressions of arousal (or anxiety) or
      with aggressive behaviors exhibited during testing. We conclude that in female
      cynomolgus monkeys, social impulsivity (vs. inhibition) correlates inversely with
      individual differences in CNS serotonergic activity, as assessed by
      neuroendocrine challenge.

PMID- 14669271
TI  - Short-term biologic response to withdrawal of hormone replacement therapy in
      patients with invasive breast carcinoma.
AB  - BACKGROUND: The biologic effect of continuing hormone replacement therapy (HRT)
      after a diagnosis of breast carcinoma is unclear. The goal of rhe current study
      was to determine the short-term effect of HRT withdrawal on invasive breast
      carcinoma using biologic surrogate markers of tumor response. METHODS: The study
      was performed between 1996 and 2000 and comprised 140 women who had been using
      HRT at the time of breast carcinoma diagnosis by core needle biopsy. The breast
      tumors were removed a median of 17 days later (range, 2-31 days). Of these women,
      125 women stopped HRT at the time of core needle biopsy and 15 continued to
      receive HRT until surgery. In addition, 55 women with breast carcinoma from the
      same time period, who were not receiving HRT at diagnosis, were studied. Changes
      in expression of Ki-67 (a measure of epithelial cell proliferation), progesterone
      receptor (PR), p27KIP-1 (a cyclin-dependent kinase inhibitor), and cyclin D1 (a
      cell cycle-related protein) were determined by immunohistochemistry on paired
      sections of the core needle biopsy and surgical specimens from each patient.
      RESULTS: In women who stopped HRT, a significant decrease in Ki-67 expression was
      observed between core needle biopsy and surgery in estrogen receptor (ER)
      positive (n = 106; P < 0.001), but not in ER-negative tumors (n = 19; P = 0.58),
      with an associated reduction in PR (P < 0.001) and cyclin D1 expression (P <
      0.001) and an increase in p27KIP-1 (P = 0.03). These changes in Ki-67 and PR
      expression occurred irrespective of c-erb-B2 status. No change was observed in
      any parameter in the other groups of patients. CONCLUSIONS: ER-positive invasive
      breast carcinomas demonstrated a favorable biologic response to withdrawal of
      HRT. Therefore, HRT should be stopped at the time of diagnosis and was
      subsequently contraindicated.

PMID- 14669272
TI  - Do we need HER-2/neu testing for all patients with primary breast carcinoma?
AB  - BACKGROUND: HER-2/neu is a valuable prognostic marker in primary breast
      carcinoma. Controversy surrounds the correlation between HER-2/neu expression and
      other prognostic markers, as has been discussed in preclinical and clinical
      studies. The objective of the current study was to investigate the probability,
      calculated using parameters that are assessed routinely in clinical practice,
      that patients with breast carcinoma had positive HER-2/neu status. METHODS: The
      authors evaluated HER-2/neu status in 923 consecutive patients with breast
      carcinoma by immunohistochemical methods. Correlations involving HER-2/neu
      status, estrogen receptor (ER) and progesterone receptor (PR) status, tumor
      grade, patient age, lymph node involvement, and tumor size were evaluated using
      the Mantel-Haenszel chi-square test and the Spearman correlation. The authors
      created a simple scoring system (i.e., the diagnostic instrument for validation
      of HER-2/neu score) to define subgroups of patients with breast carcinoma and to
      determine the likelihood of HER-2/neu positivity. RESULTS: HER-2/neu
      overexpression was correlated significantly with negative ER (P = 0.0001) and PR
      status (P = 0.0001), Grade 3 (G3) lesions (P = 0.0001), and young age (P =
      0.006). The likelihood of HER-2/neu positivity in a patient with positive ER and
      PR status and G1/G2 disease was approximately 6.1%. CONCLUSIONS: The authors
      demonstrated in a large patient series that HER-2/neu overexpression was
      associated with negative hormone receptor status, G3, and young age. In a
      subgroup of patients presenting with hormone-responsive and G1/G2 tumors, the
      likelihood of HER-2/neu overexpression was very small. Therefore, the assessment
      of HER-2/neu status in this subgroup of patients with breast carcinoma may be
      considered unnecessary, unless the role of HER-2/neu status in adjuvant treatment
      has been proven.

PMID- 14669273
TI  - Correlation of Bcl-2 and p53 expression in primary breast tumors and
      corresponding metastatic lymph nodes.
AB  - BACKGROUND: The p53 tumor suppressor gene product participated in G1 cell cycle
      arrest or cell death. Loss of function was associated with poor outcome in
      patients with breast carcinoma. bcl-2 prevented apoptosis induced by c-myc or
      growth factor deprivation. High bcl-2 expression in breast tumor tissue specimens
      appears to be associated with favorable prognostic factors. However, Bcl-2 and
      p53 expression in primary tumor tissue specimens versus metastatic lymph node
      specimens in breast carcinoma has not been studied. The current study compared
      Bcl-2 and p53 expression in primary breast carcinoma tissue specimens with Bcl-2
      and p53 expression in axillary lymph node specimens. METHODS: Primary breast
      tumor and corresponding axillary metastatic lymph node tissue specimens were
      obtained from 60 patients with breast carcinoma. They were evaluated for the
      presence of Bcl-2 and p53 expression by immunohistochemistry using standard
      methods. RESULTS: Bcl-2 expression in primary tumor tissue specimens (53%) was
      correlated with Bcl-2 expression in metastatic lymph node specimens (50 %;
      Pearson correlation = 0.656). p53 expression in primary tumor specimens (72%) was
      correlated with p53 expression in metastatic lymph node specimens (60 %; Pearson
      correlation = 0.800). A significant inverse correlation also was found between
      p53 and Bcl-2 expression in primary breast tumor tissue specimens (Pearson
      correlation = -0.310). CONCLUSIONS: The current study suggested that Bcl-2 and
      p53 expression in axillary metastatic lymph node specimens is correlated with Bcl
      2 and p53 expression in the primary tumor tissue specimens. The prognostic and
      predictive value of Bcl-2 and p53 expression in axillary lymph node metastasis in
      patients with breast carcinoma needs to be further evaluated in larger trials
      with longer follow-up.

PMID- 14669274
TI  - Prognostic significance of Gleason pattern in patients with Gleason score 7
      prostate carcinoma.
AB  - BACKGROUND: In the current study, the authors sought to further stratify the
      prognosis of patients with Gleason score (GS) 7 prostate carcinoma. They assessed
      the influence on outcome of a predominant poorly differentiated Gleason pattern
      (primary Gleason pattern [GP] 4) and/or a coincident small focus of poorly
      differentiated tumor of higher grade (tertiary GP 5). METHODS: The authors
      studied 412 patients (mean postoperative follow-up, 33 months) with GS 7 tumors
      treated with radical prostatectomy at a single Australian campus between November
      1989 and December 2002. The chi-square test, Kaplan-Meier method, and Cox
      proportional hazards analyses were used to evaluate the correlation between
      primary GP 4 and tertiary GP 5 with the occurrence of adverse pathologic features
      and disease recurrence. RESULTS: In this cohort, 307 patients (75%) had primary
      GP 3 tumors, 105 (25%) had primary GP 4 tumors, and 17 (2.3%) had a tertiary
      element of high-grade tumor (GP 5). Patients with primary GP 4 tumors displayed
      higher rates of seminal vesicle involvement and extraprostatic extension and,
      along with patients with tertiary GP 5, had significantly shorter times to
      disease recurrence. Univariate analysis demonstrated that primary GP 4 (P =
      0.0003) and tertiary GP 5 (P < 0.0001) were strong predictors of disease
      recurrence. Primary GP 4 (P = 0.0122) remained an independent predictor of
      disease recurrence on stepwise multivariate analysis. CONCLUSIONS: Primary GP 4
      tumors represented an aggressive subset of GS 7 prostate carcinomas. Primary GP
      was an easily accessible and clinically relevant predictor of disease recurrence
      in patients with GS 7 prostate carcinoma.

PMID- 14669275
TI  - Scoring algorithm to predict survival after nephrectomy and immunotherapy in
      patients with metastatic renal cell carcinoma: a stratification tool for
      prospective clinical trials.
AB  - BACKGROUND: The objective of this study was to develop an algorithm capable of
      stratifying the survival of patients with metastatic renal cell carcinoma (RCC)
      after nephrectomy and immunotherapy. METHODS: The medical records of 173 patients
      who underwent radical nephrectomy for metastatic RCC and received recombinant
      interleukin-2 (IL-2)-based immunotherapy between 1989 and 2000 were evaluated.
      Survival was the primary endpoint and was assessed based on clinical, surgical,
      and pathologic parameters. The clinical parameters included age, gender,
      performance status, existing hypertension, thyroid-stimulating hormone (TSH)
      levels, location of metastases, and presenting symptomatology. The surgical
      features included the requirement for blood transfusion or adrenalectomy. The
      pathologic factors involved tumor stage, tumor size, nuclear grade, lymph node
      status, and histologic subtype. Disease-specific survival was estimated using the
      Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models
      were used to determine associations between clinical and pathologic features and
      survival. RESULTS: The median follow-up was 3.2 years (range, 0.2-9.3 years).
      Death due to RCC occurred in 123 patients (71%) at a median of 13 months (range,
      from 0.1 months to 8.4 years) after nephrectomy. Multivariate analysis revealed
      that the following features were associated with survival: lymph node status (P =
      0.002), constitutional symptoms (P = 0.005), location of metastases (P < 0.001),
      sarcomatoid histology (P = 0.003), and TSH level (P = 0.038). A scoring system
      based on the features in the multivariate model was created to stratify patients
      into low-risk, intermediate-risk, and high-risk groups. Estimated survival rates
      at 1 years, 3 years, and 5 years were 92%, 61%, and 41%, respectively, for the
      low-risk group and 66%, 31%, and 19%, respectively, for the intermediate risk
      group. The high-risk group had 1% survival at 1 year and no survivors at 3 years.
      CONCLUSIONS: In patients with metastatic RCC who were treated with nephrectomy
      and IL-2 immunotherapy, regional lymph node status, constitutional symptoms,
      location of metastases, sarcomatoid histology, and TSH levels were associated
      with survival. The authors present a scoring algorithm based on these features
      that can be used to predict survival in patients who present with metastatic RCC
      and to stratify such patients for prospective clinical trials.

PMID- 14669276
TI  - Prostate carcinoma tissue proteomics for biomarker discovery.
AB  - BACKGROUND: The advent of the prostate-specific antigen (PSA) test has had a
      profound impact on the diagnosis and treatment of prostate carcinoma. However,
      the use of PSA levels alone for screening for prostate carcinoma was compromised
      by the variations in the amount of PSA produced by the benign prostatic tissue
      specimens. Proteins were involved in various pathways that determine the behavior
      of a cell. Therefore, information regarding proteins may reveal drug targets
      and/or markers for early detection. METHODS: The authors used surface-enhanced
      laser desorption/ionization time-of-flight mass spectrometry to determine the
      protein profiles from fresh tissues of the prostate. Laser capture
      microdissection was performed to isolate pure populations of cells. RESULTS: The
      authors identified a protein with an average m/Z of 24,782.56 +/- 107.27 that was
      correlated with the presence of prostate carcinoma. Furthermore, using laser
      capture microdissection, they demonstrated that the origin of this protein, which
      the authors designated PCa-24, was derived from the epithelial cells of the
      prostate. PCa-24 expression was detected in 16 of 17 (94%) prostate carcinoma
      specimens but not in paired normal cells. In addition, this protein was not
      expressed in any of the 12 benign prostatic hyperplasia specimens that were
      assayed. CONCLUSIONS: PCa-24 may be useful a marker for prostate carcinoma.

PMID- 14669277
TI  - Quantitative alterations in nuclear structure predict prostate carcinoma distant
      metastasis and death in men with biochemical recurrence after radical
      prostatectomy.
AB  - BACKGROUND: Microscopic histologic grade has been the best predictor of prostate
      carcinoma (PCa) progression in men after surgical therapy. The ability to predict
      accurately, at the time of surgery, which patients are likely to develop
      metastatic PCa would enable optimization of disease management with adjuvant
      therapy. The authors assessed the ability of pathologic, nuclear morphometric,
      and chromatin parameters to predict metastatic PCa progression and/or death in
      227 men with biochemical recurrence and long-term follow-up after undergoing
      radical prostatectomy. METHODS: Multivariate logistic regression (LR) was used to
      calculate quantitative nuclear grade (QNG) solutions using the variances of 60
      nuclear morphometric descriptors (NMDs) of nuclear size, shape, DNA content, and
      chromatin organization that predicted distant metastasis and/or PCa-specific
      death. An LR model also was generated to predict this outcome using a combination
      of pathologic variables and the best QNG solution. Cox proportional hazards
      models were generated, and Kaplan-Meier plots were used to display three risk
      groups based on pathology, QNG, and a combination of these variables. RESULTS: A
      multivariate LR model using pathology retained lymph node (LN) status, seminal
      vesicle status, and prostatectomy Gleason score, yielding an area under the curve
      receiver operator characteristic (AUC-ROC) of 75% with an accuracy of 59% at 90%
      sensitivity. The best QNG solution used the variance of 25 NMDs, yielding an AUC
      ROC of 84% and an accuracy of 70% at 90% sensitivity. The combined pathology-QNG
      model retained LN status, prostatectomy Gleason score, and QNG, yielding an AUC
      ROC of 86% with an accuracy of 76% at 90% sensitivity. The Cox proportional
      hazards models produced the following significant univariate and multivariate
      hazard ratios: QNG, 3.5 and 2.9, respectively; LN, 2.7 and 1.8, respectively; and
      prostatectomy Gleason score, 2.8 and 2.1, respectively. CONCLUSIONS: Alterations
      in the structure of tumor nuclei measured by computer-assisted image analysis
      were strong predictors of PCa progression and death in men with long-term follow
      up who had biochemical recurrence after undergoing radical prostatectomy. QNG
      solutions can serve as a new supplemental biomarker for accurate prediction of
      PCa progression at the time of surgery.

PMID- 14669278
TI  - A phase II study of estramustine, docetaxel, and carboplatin with granulocyte
      colony-stimulating factor support in patients with hormone-refractory prostate
      carcinoma: Cancer and Leukemia Group B 99813.
AB  - BACKGROUND: The authors determined the safety and efficacy of estramustine,
      docetaxel, and carboplatin with granulocyte-colony-stimulating factor (G-CSF)
      support in patients with hormone-refractory prostate carcinoma. METHODS: In the
      current multicenter, cooperative group study, patients with advanced prostate
      carcinoma whose disease progressed despite androgen deprivation therapy were
      treated with a combination of oral estramustine(240 mg three times per day for 5
      days), 70 mg/m2 of docetaxel, and carboplatin at a dose of (area under the curve)
      5. G-CSF was used to minimize the neutropenia associated with this regimen. Each
      cycle was repeated every 21 days. RESULTS: Forty patients were treated with a
      median of 7 cycles of therapy. Of the 34 evaluable patients with elevated
      pretreatment prostate-specific antigen (PSA) levels, 23 (68%) had a > or = 50%
      decline in PSA and 20 (59%) had a > or = 75% decline. Twenty-one patients had
      measurable disease, with 1 complete response (5%) and 10 partial responses (47%),
      for an overall measurable response rate of 52% (95% confidence interval [95% CI],
      30-74%). The most common Grade 3 or Grade 4 toxicities (according to the National
      Cancer Institute Common Toxicity Criteria) included neutropenia in 23% of
      patients, thrombocytopenia in 13%, and fatigue in 13%. Febrile neutropenia
      occurred in 1 patient (3%). The overall median time to disease progression was
      8.1 months (95% CI, 6-10 months) and the overall survival period was 19 months
      (95% CI, 13-26 months). CONCLUSIONS: The combination of estramustine, docetaxel,
      and carboplatin with G-CSF support was found to have significant clinical
      activity with an acceptable toxicity profile in patients with progressive hormone
      refractory prostate carcinoma.

PMID- 14669279
TI  - Prophylactic oophorectomy: a morphologic and immunohistochemical study.
AB  - BACKGROUND: The tumorigenesis of ovarian carcinoma is poorly understood. The
      authors studied morphologic features and immunohistochemical expression patterns
      of neoplasia-associated markers in prophylactically removed ovaries, normal
      ovaries, and papillary serous ovarian carcinomas to identify possible
      preneoplastic changes in ovarian surface epithelium. METHODS: Morphologic
      features and immunohistochemical expression patterns of CA-125, Ki-67, p53, E
      cadherin, and Bcl-2 were evaluated in 21 normal ovaries, 31 ovaries that were
      removed prophylactically for increased carcinoma risk, and 7 ovarian papillary
      serous carcinomas. Representative slides from formalin-fixed, paraffin-embedded
      tissue blocks were submitted to immunohistochemical staining and were evaluated
      independently by three gynecologic pathologists. For statistical analyses, Fisher
      exact tests, multivariate analyses, Spearman rank correlation coefficients, Wald
      statistics, Kruskal-Wallis tests, and Mann-Whitney tests were used.
      Immunohistochemical staining results were correlated with morphologic findings.
      RESULTS: The authors found progressive increases in reactivity with the lowest
      expression in normal ovarian epithelium, stronger expression in epithelium from
      prophylactically removed ovaries, and the highest expression in carcinomas for Ki
      67 and p53. A similar trend was observed for CA-125. Positivity for Ki-67 and p53
      was seen predominantly in the epithelium of inclusion cysts and deep
      invaginations, including those areas that had been identified as hyperplastic or
      dysplastic on routine hematoxylin and eosin-stained sections. CONCLUSIONS: The
      current results suggest biologic/molecular evidence for the existence of
      preneoplastic changes in ovarian surface epithelium and support the previously
      proposed concept of ovarian dysplasia. Subtle morphologic alterations of the
      ovarian epithelium may be biologically significant.

PMID- 14669280
TI  - Loss of surface and cyst epithelial basement membranes and preneoplastic
      morphologic changes in prophylactic oophorectomies.
AB  - BACKGROUND: The authors suggested that the loss of collagen IV and laminin
      containing basement membrane and the loss of Disabled-2 (Dab2) expression were
      two critical events associated with morphologic dysplastic changes of the ovarian
      surface epithelium as a step in tumorigenicity. Both the basement membrane and
      Dab2, a candidate tumor suppressor of ovarian carcinoma, were involved in
      epithelial cell surface positioning and organization. The authors speculated that
      the purging of the basement membrane may be similar to the proteolysis during
      gonadotropin-stimulated ovulation, a cyclooxygenase 2 (Cox-2)-mediated process.
      METHODS: Prophylactic oophorectomy is used to prevent breast and ovarian
      carcinoma in high-risk populations. These ovarian tissue specimens often contain
      an increased presence of morphologically abnormal lesions that are believed to be
      preneoplastic. The authors evaluated archived prophylactic oophorectomy specimens
      to verify whether the loss of Dab2 expression and the removal of the basement
      membrane that occur at the ovarian surface and inclusion cyst epithelia are
      molecular markers of preneoplastic lesions. Of the 36 samples containing
      identifiable ovarian surface epithelial components on slides, immunostaining was
      employed to evaluate the intactness of the basement membrane (periodic acid
      Schiff [PAS], collagen IV, and laminin) and the expression of Dab2 and Cox-2.
      Expression of Cox-1 and Cox-2 also were evaluated in cultured ovarian surface
      epithelial cells prepared from ovarian tissue specimens removed from patients who
      underwent prophylactic surgery. RESULTS: The morphologically normal ovarian
      surface epithelium typically contained a collagen IV- and laminin-positive
      basement membrane, which also was detected by PAS staining. Many morphologically
      altered areas, such as papillomatosis, invaginations, inclusion cysts,
      stratification, adenomas, and microscopic adenocarcinomas, were found in these
      specimens. Both the morphologically altered and adjacent morphologically normal
      epithelia consistently exhibited loss of basement membrane and/or Dab2 expression
      and an increase in Cox-2 staining. Frequently, an increase in Cox-2 staining was
      correlated with the loss of epithelial basement membrane in morphologically
      normal areas. CONCLUSIONS: The loss of Dab2 and basement membrane and the
      overexpression of Cox-2 were observed in presumptive neoplastic precursor areas
      of oophorectomy specimens obtained from a population at high risk for ovarian
      carcinoma. Transient loss of collagen IV and laminin in the basement membrane of
      the preneoplastic epithelium and the loss of Dab2 expression are common early
      events associated with morphologic alteration and tumorigenicity of the ovarian
      surface epithelium. The authors concluded that Cox-2 overexpression may play a
      role in the purging of basement membrane of the ovarian surface epithelium,
      mimicking the process of ovulation. Further experiments may be able to test the
      hypothetical model derived from these histologic observations.

PMID- 14669281
TI  - The value of routine follow-up in patients treated for carcinoma of the vulva.
AB  - BACKGROUND: Vulvar carcinoma patients traditionally are offered follow-up after
      their primary treatment because earlier diagnosis of recurrent disease is
      believed to improve chances for curative treatment. The objective of the current
      study was to determine the value of a strict routine follow-up protocol for the
      detection of recurrences in a large series of patients who were treated for
      carcinoma of the vulva. METHODS: Clinicopathologic data for patients with primary
      squamous cell carcinoma of the vulva who were treated between January 1990 and
      July 2000 were prospectively stored in a database. After treatment, patients
      visited the outpatient clinic at the study institution at gradually increasing
      intervals. When a recurrence was diagnosed, it was indicated whether the
      recurrence was local, occurred in the skin bridge, occurred in the inguinal
      region, or was distant, and this information was registered. Moreover, it was
      noted whether the diagnosis was made at a routinely scheduled or at an interval
      follow-up meeting and whether symptoms as noted by the patient herself led to the
      diagnosis. RESULTS: Data from 238 patients with International Federation of
      Gynecology and Obstetrics (FIGO) Stage I-IV vulvar carcinoma were analyzed with a
      mean follow-up of 63 months (median, 58 months; range, 6-149 months). Sixty-five
      of 238 patients (27%) developed recurrent disease; 49 were local recurrences, 2
      recurrences were found in the skin bridge, 6 were found in the inguinal region,
      and 8 were distant recurrences. Forty-two of these 65 recurrences (65%) were
      detected at a routinely scheduled follow-up meeting, at which time 21 of the 42
      patients with recurrent disease (50%) reported symptoms or signs. Local
      recurrences diagnosed at a routinely scheduled follow-up meeting were found to
      have a smaller greater dimension (mean, 2.1 cm and median, 1.6 cm; range, 0.3-8.0
      cm) compared with recurrences detected at an interval meeting (mean, 3.1 cm and
      median, 3.0 cm; range, 0.4-7.0 cm) (P = 0.04). CONCLUSIONS: The data from the
      current study indicated that routinely scheduled follow-up meetings with patients
      with carcinoma of the vulva result in the detection of smaller recurrences in a
      substantial proportion of patients compared with self-reported recurrences,
      without a measurable effect on morbidity or mortality.

PMID- 14669282
TI  - Long-term follow-up of autologous stem cell transplantation in patients with
      diffuse mantle cell lymphoma in first disease remission: the prognostic value of
      beta2-microglobulin and the tumor score.
AB  - BACKGROUND: The current study was conducted to analyze the long-term results of
      autologous stem cell transplantation (ASCT) in patients with diffuse mantle cell
      lymphoma (MCL) in first disease remission. METHODS: Thirty-three patients were
      treated. Thirty-one patients had Ann Arbor Stage III or Stage IV disease. The
      hyper-CVAD regimen (hyperfractionated intense-dose cyclophosphamide, vincristine,
      continuous intravenous infusion of doxorubicin, and dexamethasone, alternating
      with high doses of cytarabine and methotrexate plus leucovorin rescue) was used
      for cytoreduction before ASCT. Patients were consolidated with high-dose
      cyclophosphamide (120 mg/kg), total body irradiation, and ASCT. RESULTS: At a
      median follow-up of 49 months, the overall survival and disease-free-survival
      rates at 5 years were estimated to be 77% and 43%, respectively. Patients whose
      M. D. Anderson Lymphoma Tumor Score (TS) was < or = 1 at the time of diagnosis or
      transplantation experienced longer disease-free survival compared with those
      whose TS was > 1 (P = 0.02). A beta2-microglobulin (beta2m)level < or = 3 mg/L at
      the time of diagnosis or transplantation was also found to be strongly predictive
      of longer survival (5-year survival rate of 100% vs. 22% in patients with a
      beta2m level > 3 mg/L) (P = 0.0001). CONCLUSIONS: ASCT may prolong the overall
      survival in a subset of patients with MCL. This improvement has been observed for
      the most part in patients with low beta2m levels (< or = 3 mg/L) and TS (< or =
      1). Randomized trials are required to fully assess the benefits of this strategy.

PMID- 14669283
TI  - Imatinib mesylate therapy improves survival in patients with newly diagnosed
      Philadelphia chromosome-positive chronic myelogenous leukemia in the chronic
      phase: comparison with historic data.
AB  - BACKGROUND: The International Randomized study of Interferon-alpha plus
      cytarabine (IFN-alpha plus ara-C) versus STI571 (imatinib mesylate) [IRIS trial]
      in patients with newly diagnosed Philadelphia chromosome (Ph)-positive, chronic
      phase chronic myelogenous leukemia (CML) has not shown (to date) a survival
      advantage for imatinib. This was most likely because approximately 90% of
      patients receiving IFN-alpha plus ara-C changed to imatinib therapy after a
      median of 8 months into therapy. METHODS: The authors analyzed the results with
      imatinib therapy in patients with newly diagnosed Ph-positive CML in chronic
      phase and compared their outcome with patients who received IFN-alpha regimens. A
      total of 187 patients with Ph-positive CML in early chronic phase treated with
      imatinib were compared with a historic group of 650 similar patients treated with
      IFN-alpha regimens from 1982 until 1997. RESULTS: Patients who received imatinib
      were significantly older and had significantly more bone marrow basophilia and
      less leukocytosis. The complete cytogenetic response (Ph 0%) rates were better
      with imatinib (81% vs. 32%; P < 0.001), as were the survival rates (30-month
      estimated survival rates 98% vs. 88%; P = 0.01). A multivariate analysis of the
      total study group of 837 patients identified imatinib therapy to be a significant
      independent favorable prognostic factor for survival (P = 0.01). CONCLUSIONS: The
      current study is the first to indicate the survival advantage of imatinib
      compared with IFN-alpha, the previous standard of care, in patients with early
      chronic-phase CML.

PMID- 14669284
TI  - Imatinib mesylate in Philadelphia chromosome-positive leukemia of childhood.
AB  - BACKGROUND: Initial treatment for adult patients with Philadelphia chromosome
      positive (Ph[+]) chronic myelogenous leukemia (CML) now includes imatinib
      mesylate. However, to our knowledge, there are few data regarding imatinib
      safety, efficacy, and response monitoring in patients age < 18 years. METHODS: In
      the current series, the authors report 5 consecutive patients ages 20 months to
      12 years with Ph+ leukemia who were treated with imatinib and evaluated for a
      response using cytogenetics, fluorescent in situ hybridization (FISH), and real
      time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on
      serial bone marrow aspirations. Doses of imatinib were escalated as tolerated
      from a starting dose of 400 mg/m2 (patients with a body surface area [BSA] < 1
      m2) or 400 mg/day (patients with a BSA > 1 m2). RESULTS: After the initiation of
      imatinib therapy, all 4 patients with CML were found to have no detectable Ph
      chromosome by cytogenetics (median of 198 days of imatinib therapy; range, 138
      346 days), FISH (median of 285 days of imatinib therapy; range, 138-366 days),
      and real-time RT-PCR (median of 287 days of imatinib therapy; range, 224-366
      days). One patient with Ph+ acute mixed lineage leukemia achieved a morphologic
      disease remission with standard chemotherapy, but within 10 months had increasing
      Ph positivity in consecutive bone marrow aspirations. Imatinib was added to the
      intensive leukemia therapy, and within 26 days there were no detectable Ph+ cells
      in the bone marrow. Mild thrombocytopenia was noted in two patients and transient
      mild hepatic toxicity was noted in one patient. CONCLUSIONS: Imatinib mesylate
      was found to be effective in inducing undetectable residual disease in a small
      cohort of pediatric patients with Ph+ leukemia. Further studies of the use of
      imatinib in childhood Ph+ malignancies are needed.

PMID- 14669285
TI  - Doxorubicin-based chemotherapy for diffuse large B-cell lymphoma in elderly
      patients: comparison of treatment outcomes between young and elderly patients and
      the significance of doxorubicin dosage.
AB  - BACKGROUND: Although many studies of elderly patients with non-Hodgkin lymphoma
      have focused on the dose intensity of chemotherapy, few studies have restricted
      the histologic inclusion criteria such that only patients with diffuse large B
      cell lymphoma (DLCL) are considered. In the current study, treatment outcomes for
      elderly patients (age > or = 60 years) were analyzed, with emphasis on the dose
      intensity of doxorubicin. METHODS: Between 1994 and 2000, 195 patients with DLCL
      were treated initially with doxorubicin-based chemotherapy (cyclophosphamide,
      doxorubicin, vincristine, and prednisone; or cyclophosphamide, vincristine,
      bleomycin, doxorubicin, procarbazine, and prednisone). Of these patients, 70 were
      aged 60 years or older. RESULTS: Elderly patients had poorer treatment outcomes
      than did young patients (5-year survival, 30% vs. 57%; P < 0.001); however,
      elderly patients who received doxorubicin at dose intensities > or = 10 mg/m2 per
      week (n = 25) had outcomes (5-year survival, 52%) that were comparable to those
      of young patients. Among prognostic factors, only International Prognostic Index
      score (P = 0.022) and dose intensity of doxorubicin (P = 0.039) were found to
      have significant effects on the overall survival of elderly patients. When the
      reasons for doxorubicin dose reduction in 45 elderly patients who ultimately
      received doxorubicin at dose intensities < 10 mg/m2 per week were analyzed, it
      was found that 20 patients received reduced doses from the start of treatment
      because of their old age alone; these dose reductions in the 20 cases resulted in
      poorer treatment outcomes. CONCLUSIONS: Elderly patients with DLCL who received
      doxorubicin at dose intensities > or = 10 mg/m2 per week had treatment outcomes
      that were comparable to those of young patients; however, physician bias
      associated with patient age was found to be related to unnecessary dose
      reductions. Efforts to maintain doxorubicin dose intensities > or = 10 mg/m2 per
      week and more objective standards for the selection of elderly patients capable
      of tolerating doxorubicin-based regimens are required.

PMID- 14669286
TI  - Alemtuzumab as treatment for residual disease after chemotherapy in patients with
      chronic lymphocytic leukemia.
AB  - BACKGROUND: The objective of this study was to investigate the efficacy and
      safety of alemtuzumab, the humanized anti-CD52 monoclonal antibody, in patients
      with B-cell chronic lymphocytic leukemia and residual disease after chemotherapy.
      METHODS: Forty-one patients received alemtuzumab 3 times weekly for 4 weeks. The
      first 24 patients received 10 mg per dose, and the next 17 patients received 30
      mg. All patients received infection prophylaxis during therapy and for 2 months
      after treatment. RESULTS: The overall response rate was 46%, including 39% of
      patients who received the 10 mg dose and responded versus 56% of the patients who
      received the 30 mg dose. The major reason for failure to respond was the presence
      of adenopathy. Residual bone marrow disease cleared in most patients, and 11 of
      29 patients (38%) achieved a molecular disease remission. The median time to
      disease progression had not been reached in responders with a median follow-up of
      18 months. Six patients remained in disease remission between 24-38 months after
      therapy. Infusion-related events were common with the initial doses, but all such
      events were NCI Common Toxicity Criteria Grade 1-2. Infections were reported to
      occur in 15 patients (37%), and 9 of these infections were reactivation of
      cytomegalovirus. Three patients developed Epstein-Barr virus positive, large cell
      lymphoma. Two patients had spontaneous resolution of the lymphoma and, in one
      patient, the lymphoma resolved after treatment with cidofovir and immunoglobulin.
      CONCLUSIONS: Alemtuzumab produced significant responses in patients with residual
      disease after chemotherapy. Bone marrow disease was eradicated more frequently
      than lymph node disease, and molecular disease remissions were achieved. A
      randomized trial comparing alemtuzumab with observation after chemotherapy is
      indicated.

PMID- 14669287
TI  - Gemcitabine plus oxaliplatin for patients with advanced hepatocellular carcinoma
      using two different schedules.
AB  - BACKGROUND: New therapies are needed to improve the prognosis of patients with
      advanced hepatocellular carcinoma (HCC). Various gemcitabine-oxaliplatin
      combinations have been tested recently in patients with ovarian and pancreatic
      carcinoma, yielding interesting results with little toxicity. Therefore, the
      authors evaluated the activity and toxicity of two such combinations in patients
      with HCC. METHODS: Twenty-one patients were enrolled prospectively in the study.
      Eleven patients received gemcitabine 1000 mg/m2 on Day 1 and oxaliplatin 100
      mg/m2 on Day 2 (GEMOX-1), and 10 patients received gemcitabine 1500 mg/m2 on Day
      1 followed by oxaliplatin 85 mg/m2 on Day 1 (GEMOX-2). Treatment was repeated
      every 2 weeks until disease progression developed or until unacceptable adverse
      effects occurred. RESULTS: All patients were assessable for response and
      toxicity. Four patients (19%) achieved objective responses (95% confidence
      interval, 13-26%), including 3 patients in the GEMOX-1 group and 1 patient in the
      GEMOX-2 group. Ten patients (48%) had stable disease, and 7 patients (33%)
      experienced disease progression. The median progression-free survival was 5
      months, and the median overall survival was 12 months. Fifty-four percent of
      patients in the GEMOX-1 group and 50% of patients in the GEMOX-2 group had
      received previous systemic chemotherapy or cisplatin-based chemoembolization.
      Grade 3-4 hematologic toxicity, according to National Cancer Institute Common
      Toxicity Criteria, consisted of thrombocytopenia (GEMOX-1 vs. GEMOX-2, 18% vs.
      40%) and neutropenia (0% vs. 30%). No Grade 3-4 nonhematologic toxicity was
      observed, except for 1 episode of Grade 3 diarrhea. Grade 1 neurotoxicity and
      Grade 2 neurotoxicity (specific scale), respectively, were observed in 4 patients
      and 7 patients receiving GEMOX-1 and in 7 patients and 1 patient receiving GEMOX
      2. CONCLUSIONS: Gemcitabine-oxaliplatin combination therapy is feasible in
      patients with advanced HCC. The GEMOX-1 regimen was tolerated better than the
      GEMOX-2 regimen. Currently, the GEMOX-1 regimen is being evaluated in a Phase II
      study in previously untreated patients with HCC.

PMID- 14669288
TI  - The des-gamma-carboxy prothrombin index is a new prognostic indicator for
      hepatocellular carcinoma.
AB  - BACKGROUND: Des-gamma-carboxy prothrombin (DCP) has been reported to be an
      important prognostic factor in patients with hepatocellular carcinoma (HCC).
      Recently, a monoclonal antibody, 19B7, which recognizes the Gla domain of DCP,
      has been identified. The 19B7 antibody recognizes an epitope different from that
      recognized by MU-3, which is another antibody against DCP. In this study, the
      authors investigated the measurement of DCP using the antibodies MU-3 and 19B7,
      respectively, as a prognostic factor for patients with HCC who had solitary,
      small tumors and or Child Stage A HCC. METHODS: One hundred four patients with
      HCC who had solitary, small tumors or Child Stage A tumors were enrolled in the
      study between 1991 and 2001. All patients were treated and were followed for a
      mean of 3.2 years. The authors analyzed the correlation between the DCP Index
      (DCP measured by MU-3 and DCP measured by 19B7) and patient prognosis. The
      patients were classified into 3 groups based on their DCP Index: 1) DCP negative
      (DCP < 40 milli arbitrary unit (mAU)/mL)); 2) low DCP Index (DCP > or = 40
      mAU/mL; MU-3:19B7 ratio, < 3.0; and 3) high DCP Index (DCP > or = 40 mAU/mL; MU
      3:19B7 ratio, > or = 3.0). RESULTS: The survival rate for patients in the high
      DCP Index group was lower compared with the survival rate for patients in the DCP
      negative group and was significantly lower compared with the survival rate for
      patients in the low DCP Index group. In a univariate Cox proportional hazards
      model, the positive factors were high DCP Index and low DCP Index. Among the
      positive predictive factors that were analyzed using a multivariate Cox
      proportional hazards model were age (hazard ratio, 3.27; P = 0.006), low DCP
      Index (hazard ratio, 2.87; P = 0.012), and high DCP Index (hazard ratio, 12.3; P
      < 0.0001). CONCLUSIONS: The prognosis of patients who had a high DCP Index score
      was poorer compared with patients who had a low DCP Index score and patients who
      were classified as DCP negative. The authors concluded that the DCP Index is a
      prognostic indicator for patients with HCC.

PMID- 14669289
TI  - Salvage therapy in patients with glioblastoma: is there any benefit?
AB  - BACKGROUND: Survival after first-line therapy is poor for patients with
      glioblastoma. The role of second-line treatment for recurrent disease is
      controversial. The authors studied the outcome in a subset of patients with
      glioblastoma who were selected for an aggressive reintervention strategy at the
      time of progression. Their objectives were to improve patients' overall survival
      with sustained quality of life and to make comparisons with overall survival in
      unselected patients. METHODS: Overall, 168 patients were eligible for
      retrospective analysis. Ninety patients received specific therapy for disease
      recurrence (reintervention group) by specific criteria. RESULTS: In the
      reintervention group, promising median overall survival (mOS) results after
      diagnosis (61.5 weeks) and progression (33 weeks) were obtained. The progression
      free survival (PFS) rate at 12 months and the overall survival rate were superior
      in the reintervention group (71% at 12 months and 32% at 24 months) compared with
      the total cohort (45% and 20%, respectively) and the standard group (15% and 5%,
      respectively). A matched-pair analysis (n = 46 in each group), with an mOS period
      of 65.5 versus 28.5 weeks, confirmed these data. Quality of life was stable or
      slightly improved during reinterventions in a subset of patients treated within
      clinical studies. CONCLUSIONS: The majority of patients in the current series
      were treated with a reintervention strategy, which had an impact on PFS and mOS.
      A second resection, focal radiotherapy (in selected cases), and additional
      chemotherapeutic regimens should be considered for patients with recurrent
      glioblastoma.

PMID- 14669290
TI  - Complications in long-term survivors of Ewing sarcoma.
AB  - BACKGROUND: Multimodality treatment has dramatically improved the outcome of
      patients with Ewing sarcoma. However, there appears to be little information
      concerning treatment-related complications in patients who are long-term
      survivors. METHODS: Forty-one patients with Ewing sarcoma who were treated
      between 1960-1980 and who survived the disease by at least 20 years were included
      in the current study. In a retrospective analysis, all complications related to
      the multimodality treatment of Ewing sarcoma were assessed. RESULTS: The patient
      group was comprised of 17 men and 24 women, with a mean age at the time of
      presentation of 16.8 years (range, 5-51 years). Approximately 20% of the lesions
      were located in the pelvis. All but 9 patients (78%) received chemotherapy as
      part of their treatment. The overall follow-up period averaged 25 years (range,
      20-36 years). All except 1 patient were alive at the time of final follow-up,
      with the latter patient dying of radiation-induced secondary malignancy after 33
      years. Only 17 patients (41%) were found to be free of any complication. These
      included metastases, local recurrence, secondary malignancies, pathologic
      fractures, and radiation-associated and chemotherapy-associated morbidities.
      CONCLUSIONS: Although the patients in the current study were treated successfully
      in terms of surviving an aggressive tumor, the high complication rate in this
      group of long-term survivors is noteworthy and indicates that long-term follow-up
      should be mandatory.

PMID- 14669291
TI  - A two-arm phase II study of temozolomide in patients with advanced
      gastrointestinal stromal tumors and other soft tissue sarcomas.
AB  - BACKGROUND: The authors conducted a two-arm Phase II study of temozolomide to
      determine its efficacy and toxicity in patients with soft tissue sarcomas (STSs)
      who had received, had refused, or were not eligible for standard chemotherapy
      with doxorubicin and ifosfamide (Arm 1) and in patients with gastrointestinal
      stromal tumors (GISTs; Arm 2). Patients with GIST were eligible regardless of
      prior therapy before imatinib was available. METHODS: Sixty patients were
      enrolled in the current study, 19 of whom had GISTs and 41 of whom had other
      STSs. The patients received temozolomide at a dose of 85 mg/m2 orally for 21 days
      followed by 7 days without treatment. Standard radiographic imaging after every
      two cycles was used to assess the treatment response. RESULTS: Of the 39 patients
      in Arm 1, there was 1 complete response and 1 partial response of 39 evaluable
      patients, for a total response rate of 5% (95% confidence interval, 0-12%). The
      responses lasted 7 months and 8 months, respectively. In Arm 2, there was no
      response in 17 patients. The disease was stable in 22% of the patients with GISTs
      and 33% of the patients with other STSs. The median overall survival time was
      26.4 months in patients with GISTs and 11 months in patients with other STSs. The
      median time to disease progression was 2.3 months in patients with GISTs and 3.3
      months in patients with other STSs. Grade 3 and Grade 4 adverse effects
      (according to National Cancer Institute Common Toxicity Criteria) were rare and
      included fatigue (eight patients), anemia (six patients), constipation (four
      patients), neutropenia (four patients), and thrombocytopenia (four patients).
      CONCLUSIONS: The data from the current study suggest that temozolomide is well
      tolerated but has only minimal efficacy and a limited role in the treatment of
      patients with STSs.

PMID- 14669292
TI  - Should molecular testing be required for diagnosing synovial sarcoma? A
      prospective study of 204 cases.
AB  - BACKGROUND: The t(X;18) translocation is a specific marker of synovial sarcomas
      (SS). Detection of SYT-SSX transcripts by polymerase chain reaction (PCR) was
      tested on preselected specimens of well-established histologic types, but to our
      knowledge, the diagnostic utility of molecular assays on a series of potential SS
      in comparison with conventional tools has never been reported. METHODS: Two
      hundred four consecutive cases of potential SS submitted for a second opinion
      were studied prospectively. On the basis of clinical context, histologic aspect,
      and immunohistochemical profile, the tumors were divided into three categories:
      1) diagnosis of SS certain, when the only possible diagnosis was SS; 2) diagnosis
      of SS probable, when SS was the first diagnosis contemplated, but a differential
      diagnostic issue was raised by other tumors; 3) diagnosis of SS possible, when
      the diagnosis of SS was not the first diagnosis considered. Detection of SYT-SSX
      transcripts was performed using real-time PCR from fixed, embedded tissue as a
      systematic test. RESULTS: Sufficient RNA samples were recovered for PCR from 177
      specimens (87%). One hundred four specimens (51%) were positive for SYT-SSX
      transcripts. Tumor sites of SS included the extremities (n = 57), lung (n = 13),
      trunk wall (n = 12), head and neck (n = 6), and other sites (n = 16). There were
      61 monophasic, 22 poorly differentiated, 17 biphasic, and 4 predominantly
      epithelial SS. For 58 tumor specimens (29%), diagnosis of SS was certain before
      molecular testing; 49 (84.5%) of these 58 contained SYT-SSX transcripts. For 39
      tumor specimens (19%), diagnosis of SS was probable; 29 (74.4%) of these 39
      contained SYT-SSX transcripts. For 107 tumor specimens (52%), diagnosis of SS was
      only possible and strongly challenged by another histologic type. The issue
      consisted mainly of making the distinction between an SS and a poorly
      differentiated spindle cell sarcoma (n = 49), a poorly differentiated round cell
      sarcoma (n = 34), a carcinoma (n = 11), a myoepithelioma (n = 8), or an
      epithelioid fibrosarcoma (n = 5).Twenty-six tumor specimens (24.3%) contained SYT
      SSX transcripts-10, 7, 5, 3, and 1 in the spindle cell tumor, round cell tumor,
      carcinomalike tumor, myoepitheliomalike tumor, and epithelioid-fibrosarcoma-like
      tumor categories, respectively. CONCLUSIONS: Molecular testing was not required
      if the diagnosis of SS was certain or probable on the basis of clinical,
      histologic, and immunohistochemical evaluation. However, it proved to be very
      helpful or necessary when the diagnosis of SS was only possible and was
      challenged by other tumor types, mainly other spindle cell sarcomas, round cell
      sarcomas, carcinomas, myoepitheliomas, and epithelioid fibrosarcomas.

PMID- 14669293
TI  - Superficial radiotherapy for patients with basal cell carcinoma: recurrence
      rates, histologic subtypes, and expression of p53 and Bcl-2.
AB  - BACKGROUND: The histologic subtype of a basal cell carcinoma (BCC) may be an
      important factor for the success of a certain treatment modality. In the current
      article, the authors report recurrence rates among patients with BCC after
      superficial radiotherapy as well as Bcl-2 and p53 expression levels stratified by
      BCC subtype. METHODS: The authors performed a retrospective study of 175 BCCs in
      148 patients (64 female patients and 84 male patients; mean age, 69 years) who
      were treated with radiotherapy. According to their histologic patterns, BCCs were
      classified as nodular (n = 103), superficial (n = 25), and sclerosing (n = 47).
      In addition, six patients with metatypic BCC were reviewed. Bcl-2 and p53 protein
      expression was examined on a tissue microarray of 60 BCC samples (18 nodular
      tumors, 12 superficial tumors, and 30 sclerosing tumors). RESULTS: The estimated
      5-year recurrence rate for all patients with BCC was 15.8%: 8.2% for patients
      with the nodular subtype, 26.1% for patients with the superficial subtype, and
      27.7% for patients with the sclerosing subtype (Kaplan-Meier analysis: P =
      0.055). The median follow-up was 48 months. The mean time to recurrence was 20
      months, and 86.4% of all recurrences occurred within 3 years after treatment. No
      gender-specific differences were observed. In addition, one of six metatypic BCCs
      recurred. Nuclear p53 immunoreactivity and low Bcl-2 expression were
      significantly correlated with the sclerosing subtype. Overall, 61.5% of patients
      developed additional neoplasms during follow-up (76 developed additional BCCs, 15
      developed squamous cell carcinomas, and 6 developed Bowen disease). CONCLUSIONS:
      The sclerosing subtype of BCC was a risk factor for recurrence after
      radiotherapy. In contrast, excellent results were achieved for patients with
      predominant nodular subtype. Nevertheless, radiotherapy may be the therapy of
      choice for patients with all BCC subtypes, depending on the individual patient's
      characteristics. Expression analyses confirmed that p53 and Bcl-2 levels may be
      used as indicators for the aggressiveness of a BCC subtype. Due to the high
      incidence of additional skin malignancies, patients with BCC need careful follow
      up.

PMID- 14669294
TI  - Reassessment of the prognostic significance of hypodiploidy in pediatric patients
      with acute lymphoblastic leukemia.
AB  - BACKGROUND: The purpose of the current study was to evaluate the cytogenetic
      features of the hypodiploid leukemic cells of pediatric patients with this rare
      subgroup of acute lymphoblastic leukemia (ALL). In addition, the authors
      determined whether subdivision of the hypodiploid category served a prognostic
      purpose for these patients. METHODS: The authors evaluated the cytogenetic
      records of 979 patients with ALL admitted to St. Jude Children's Research
      Hospital (Memphis, TN) between 1984 and 1999. RESULTS: Of 67 patients (6.8%)
      whose leukemic cells contained a modal number (MN) of chromosomes less than or
      equal to 45 (i.e., hypodiploid leukemic cells), 57 had an MN of 45 and 10 had an
      MN of less than 45. In 19 patients, cells with an MN of 45 had a whole chromosome
      missing (42%), which was a sex chromosome in 12 patients (63%). Leukemic cells
      with an MN of 45 contained dicentric chromosomes (n = 33) formed from chromosome
      9p (55%), 12p (18%), or both (21%). The ETV6-CBFA2 fusion was present in 39% of
      28 evaluable B-lineage cases with an MN of 45. The event-free survival rate (EFS)
      for patients with hypodiploid leukemic cells of MN less than 45 (5-year EFS =
      20.0% +/- 10.3%) was significantly (P < 0.001) lower than that for patients with
      leukemic cells of MN greater than or equal to 45 (5-year EFS = 74.9% +/- 1.6%).
      CONCLUSIONS: Low hypodiploidy (MN < 45) should be recognized as a high-risk
      feature in pediatric ALL. Only two hypodiploid groups (MN < 45 and MN = 45) may
      be necessary in prognostic assessments.

PMID- 14669295
TI  - Music therapy for mood disturbance during hospitalization for autologous stem
      cell transplantation: a randomized controlled trial.
AB  - BACKGROUND: High-dose therapy with autologous stem cell transplantation
      (HDT/ASCT) is a commonly used treatment for hematologic malignancies. The
      procedure causes significant psychological distress and no interventions have
      been demonstrated to improve mood in these patients. Music therapy has been shown
      to improve anxiety in a variety of acute medical settings. In the current study,
      the authors determined the effects of music therapy compared with standard care
      on mood during inpatient stays for HDT/ASCT. METHODS: Patients with hematologic
      malignancy admitted for HDT/ASCT at two sites (Memorial Sloan-Kettering Cancer
      Center and Ireland Cancer Center in Cleveland, Ohio) were randomized to receive
      music therapy given by trained music therapists or standard care. Outcome was
      assessed at baseline and every 3 days after randomization using the Profile of
      Mood States. RESULTS: Of 69 patients registered in the study, follow-up data were
      available for 62 (90%). During their inpatient stay, patients in the music
      therapy group scored 28% lower on the combined Anxiety/Depression scale (P =
      0.065) and 37% lower (P = 0.01) on the total mood disturbance score compared with
      controls. CONCLUSIONS: Music therapy is a noninvasive and inexpensive
      intervention that appears to reduce mood disturbance in patients undergoing
      HDT/ASCT.

PMID- 14669296
TI  - Free interferon-alpha/beta receptors in the circulation of patients with
      adenocarcinoma.
AB  - BACKGROUND: Many viral and neoplastic diseases are resistant to interferon
      alpha/beta (IFN-alpha/beta) therapy or develop resistance during the course of
      IFN treatment. In patients with viral diseases, the authors identified four IFN
      inhibitors, of which the most important, most likely is a free IFN receptor of
      type 1 appearing in the circulation that captures and neutralizes IFN-alpha/beta.
      METHODS: Ninety-one cancer patients and 25 healthy individuals were studied. Free
      circulating IFN receptor-alpha/beta type 1 was studied. The patients were ages 35
      75 years. The diagnoses were 24 cases of colon carcinoma, 7 cases of prostate
      carcinoma, 16 cases of breast carcinoma, 8 cases of ovarian carcinoma, 9 cases of
      uterine carcinoma, 5 cases of lung carcinoma, 3 cases of astrocytoma, 4 cases of
      transitional cell carcinoma of the bladder, 1 case of osteosarcoma, 3 cases of
      multiple myeloma, 4 cases of Hodgkin disease, 2 cases of non-Hodgkin lymphoma, 3
      cases of myelodysplastic syndrome, and 2 disseminated tumors of unknown origin.
      RESULTS: All patients were found to have increased free IFN receptor-alpha/beta
      type 1 in the circulation, with the highest levels reported in patients with
      adenocarcinoma. CONCLUSIONS: High IFN inhibitory activity in patients with cancer
      may be a significant factor in their increased susceptibility to progressive
      disease, infectious complications, and resistance to IFN therapy. Ongoing studies
      are being performed with the objective of overcoming this inhibitory activity.

PMID- 14669297
TI  - Increasing the pool of academically oriented African-American medical and
      surgical oncologists.

PMID- 14669299
TI  - Mediastinal irradiation in patients with esophageal carcinoma after heart
      transplantation.

PMID- 14669300
TI  - Hospitalization of an oncology patient suspected of having severe acute
      respiratory syndrome: a setup for an infection control quagmire at a
      comprehensive cancer center.

PMID- 14669301
TI  - Classification of isolated tumor cells: clarification of the 6th edition of the
      American Joint Committee on Cancer Staging Manual.

PMID- 14669303
TI  - Reg gene family and human diseases.
AB  - Regenerating gene (Reg or REG) family, within the superfamily of C-type lectin,
      is mainly involved in the liver, pancreatic, gastric and intestinal cell
      proliferation or differentiation. Considerable attention has focused on Reg
      family and its structurally related molecules. Over the last 15 years, 17 members
      of the Reg family have been cloned and sequenced. They have been considered as
      members of a conserved protein family sharing structural and some functional
      properties being involved in injury, inflammation, diabetes and carcinogenesis.
      We previously identified Reg IV as a strong candidate for a gene that was highly
      expressed in colorectal adenoma when compared to normal mucosa based on
      suppression subtractive hybridization (SSH), reverse Northern blot, semi
      quantitative reverse transcriptase PCR (RT-PCR) and Northern blot. In situ
      hybridization results further support that overexpression of Reg IV may be an
      early event in colorectal carcinogenesis. We suggest that detection of Reg IV
      overexpression might be useful in the early diagnosis of carcinomatous
      transformation of adenoma. This review summarizes the roles of Reg family in
      diseases in the literature as well as our recent results of Reg IV in colorectal
      cancer. The biological properties of Reg family and its possible roles in human
      diseases are discussed. We particularly focus on the roles of Reg family as
      sensitive reactants of tissue injury, prognostic indicators of tumor survival and
      early biomarkers of carcinogenesis. In addition to our current understanding of
      Reg gene functions, we postulate that there might be relationships between Reg
      family and microsatellite instability, apoptosis and cancer with a poor
      prognosis. Investigation of the correlation between tumor Reg expression and
      survival rate, and analysis of the Reg gene status in human malignancies, are
      required to elucidate the biologic consequences of Reg gene expression, the
      implications for Reg gene regulation of cell growth, tumorigenesis, and the
      progression of cancer. It needs to be further attested whether Reg gene family is
      applicable in early detection of cancer and whether Reg and Reg-related molecules
      can offer novel molecular targets for anticancer therapeutics. This has
      implications with regard to prognosis, such as in monitoring cancer initiation,
      progression and recurrence, as well as the design of chemotherapeutic drugs.

PMID- 14669304
TI  - Aberrant crypt foci as microscopic precursors of colorectal cancer.
AB  - Since the first detection of aberrant crypt foci (ACF) in carcinogen-treated
      mice, there have been numerous studies focusing on these microscopically visible
      lesions both in rodents and in humans. ACF have been generally accepted as
      precancerous lesions in regard to histopathological characteristics, biochemical
      and immunohistochemical alterations, and genetic and epigenetic alterations. ACF
      show variable histological features, ranging from hyperplasia to dysplasia. ACF
      in human colon are more frequently located in the distal parts than in the
      proximal parts, which is in accordance with those in colorectal cancer (CRC). The
      immunohistochemical expressions of carcinoembryonic antigen (CEA), beta-catenin,
      placental cadherin (P-cadherin), epithelial cadherin (E-cadherin), inducible
      nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and P16INK4a are found to
      be altered. Genetic mutations of K-ras, APC and p53, and the epigenetic
      alterations of CpG island methylation of ACF have also been demonstrated. Genomic
      instabilities due to the defect of mismatch repair (MMR) system are detectable in
      ACF. Two hypotheses have been proposed. One is the "dysplasia ACF-adenoma
      carcinoma sequence", the other is "heteroplastic ACF-adenoma-carcinoma sequence".
      The malignant potential of ACF, especially dysplastic ACF, makes it necessary to
      reveal the nature of these lesions, and to prevent CRC from the earliest possible
      stage. The technique of magnifying chromoscope makes it possible to detect "in
      vivo" ACF, which is beneficial to colon cancer research, identifying high-risk
      populations for CRC, and developing preventive procedures.

PMID- 14669305
TI  - Expression properties of recombinant pEgr-P16 plasmid in esophageal squamous cell
      carcinoma induced by ionizing irradiation.
AB  - AIM: To construct the recombinant pEgr-P16 plasmid for the investigation of its
      expression properties in esophageal squamous cell carcinoma induced by ionizing
      irradiation and the feasibility of gene-radiotherapy for esophageal carcinoma.
      METHODS: The recombinant pEgr-P16 plasmid was constructed and transfected into
      EC9706 cells with lipofectamine. Western blot, quantitative RT-PCR and flow
      cytometry were performed to study the expression of pEgr-P16 in EC9706 cells and
      the biological characteristics of EC9706 cell line after transfection induced by
      ionizing irradiation. RESULTS: The eukaryotic expression vector pEgr-P16 was
      successfully constructed and transfected into EC9706 cells. The expression of P16
      was significantly increased in the transfected cells after irradiation while the
      transfected cells were not induced by ionizing irradiation. The induction of
      apoptosis in transfection plus irradiation group was higher than that in plasmid
      alone or irradiation alone. CONCLUSION: The combination of pEgr-P16 and
      irradiation could significantly enhance the P16 expression property and markedly
      induce apoptosis in EC9706 cells. These results may lay an important experimental
      basis for gene radiotherapy for esophageal carcinoma.

PMID- 14669306
TI  - Epoxide hydrolase Tyr113His polymorphism is not associated with susceptibility to
      esophageal squamous cell carcinoma in population of North China.
AB  - AIM: To investigate the possible association of microsomal epoxide hydrolase
      (mEH) Tyr113His polymorphism with susceptibility to esophageal squamous cell
      carcinoma (ESCC) in a population of North China. METHODS: The mEH Tyr113His
      genotypes were determined by polymerase-chain reaction (PCR)-restriction fragment
      length polymorphism (RFLP) analysis in 257 patients with esophageal squamous cell
      carcinoma (ESCC) and 252 healthy subjects as a control group. RESULTS: The
      frequencies for Tyr and His alleles were 44.2%, 55.8% in ESCC patients, and 44.0%
      and 56.0% in healthy subjects, respectively. No statistic difference in allele
      distribution was observed between ESCC patients and controls (chi2=0.008,
      P=0.929). The overall genotype distribution difference was not observed between
      cancer cases and controls (chi2=2.116, P=0.347). Compared with Tyr/Tyr genotype,
      neither His/His genotype nor in combination with Tyr/His genotype significantly
      modified the risk of the development of ESCC, the adjusted odds ratio was 1.076
      (95% CI=0.850-1.361) and 0.756 (95% CI=0.493-1.157), respectively. When
      stratified for sex, age, smoking status and family history of upper
      gastrointestinal cancer, His/His genotype alone or in combination with Tyr/His
      genotype also did not show any significant influence on the risk of developing
      ESCC. CONCLUSION: MEH Tyr113His polymorphism may not be used as a stratification
      marker in screening individuals at a high risk of ESCC.

PMID- 14669307
TI  - Effect of body mass index on adenocarcinoma of gastric cardia.
AB  - AIM: Obesity has been proved as one of the main risk factors for gastric cardia
      adenocarcinoma (GCA) in the West. The objective of our research was to evaluate
      the relationship between obesity and the risk of GCA in people from North China.
      METHODS: A total of 300 patients who had been diagnosed as GCA and had accepted
      surgical operation at Beijing Cancer Hospital from 1995 to 2002 were enrolled.
      Data were collected from pathology materials and hospital records. Two hundred
      and fifty-eight healthy people who had accepted health examination at the same
      hospital during the same period were enrolled as controls. Height, weight and
      gender of them at the time of examination were also collected. Obesity was
      estimated by body mass index (BMI), computed as weight in kilograms per square
      surface area (Kg/m2). The degree of obesity was determined by using BMI< or
      =18.5, 24-27.9 and > or =28 (Kg/m2) as the cut-off points for underweight/normal,
      overweight and obesity, respectively. Associations with obesity were estimated by
      odds ratios (ORs) and 95 % confidence intervals (CIs). All ORs were adjusted for
      age and sex. RESULTS: The mean level of BMI was significantly lower in the
      patient group than that in the control group. The ORs for obesity in age groups
      30-59 and 60-79 were 1.15 (95% CI=0.37-3.65) and 0.16 (95% CI=0.05-0.44) for
      males and 0.78 (95% CI=0.26-2.36) and 0.28 (95% CI=0.04-2.05) for females,
      respectively. The ORs for underweight were 2.42 (95% CI=0.56-10.53) and 4.68 (95%
      CI=1.13-19.40) for males in age subgroups 30-59 and 60-79 and 40.7 (95% CI=9.32
      177.92) for females older than 60 yrs. BMI was significantly associated with GCA
      (P<0.01). Underweight people were at high risk for GCA. CONCLUSION: BMI is an
      independent risk factor for GCA. Underweight is positively associated with GCA.

PMID- 14669308
TI  - Somatic mutation analysis of p53 and ST7 tumor suppressor genes in gastric
      carcinoma by DHPLC.
AB  - AIM: To verify the effectiveness of denaturing high-performance liquid
      chromatography (DHPLC) in detecting somatic mutation of p53 gene in gastric
      carcinoma tissues. The superiority of this method has been proved in the
      detection of germline mutations, but it was not very affirmative with respect to
      somatic mutations in tumor specimens. ST7 gene, a candidate tumor suppressor gene
      identified recently at human chromosome 7q31.1, was also detected because LOH at
      this site has also been widely reported in stomach cancer. METHODS: DNA was
      extracted from 39 cases of surgical gastric carcinoma specimen and their
      correspondent normal mucosa. Seven fragments spanning the 11 exons were used to
      detect the mutation of p53 gene and the four exons reported to have mutations in
      ST7 gene were amplified by PCR and directly analyzed by DHPLC without mixing with
      wild-type allele. RESULTS: In the analysis of p53 gene mutation, 9 aberrant DHPLC
      chromatographies were found in tumor tissues, while their normal-adjacent
      counterparts running in parallel showed a normal shape. Subsequent sequencing
      revealed nine sequence variations, 1 polymorphism and 8 mutations including 3
      mutations not reported before. The mutation rate of p53 gene (21%) was consistent
      with that previously reported. Furthermore, no additional aberrant chromatography
      was found when wild-type DNA was added into the DNA of other 30 tumor samples
      that showed normal shapes previously. The positivity of p53 mutations was
      significantly higher in intestinal-type carcinomas (40%) than that in diffuse
      type (8.33%) carcinomas of the stomach. No mutation of ST7 gene was found.
      CONCLUSION: DHPLC is a very convenient method for the detection of somatic
      mutations in gastric carcinoma. The amount of wild type alleles supplied by the
      non-tumorous cells in gastric tumor specimens is enough to form heteroduplex with
      mutant alleles for DHPLC detection. ST7 gene may not be the target gene of
      inactivation at 7q31 site in gastric carcinoma.

PMID- 14669309
TI  - Hepatic arterial infusion chemotherapy for hepatocellular carcinoma with portal
      vein tumor thrombosis.
AB  - AIM: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is
      associated with poor prognosis. The aim of this prospective study was to evaluate
      the efficacy of hepatic arterial infusion chemotherapy (HAIC) for patients with
      this disease. METHODS: Eighteen HCC patients with PVTT were treated with HAIC via
      a subcutaneously implanted injection port. A course of chemotherapy consisted of
      daily cisplatin (10 mg for one hour) followed by 5-fluorouracil (250 mg for five
      hours) for five continuous days within a given week. The patients were scheduled
      to receive four consecutive courses of HAIC. Responders were defined in whom
      either a complete or partial response was achieved, while non-responders were
      defined based on stable or progressive disease status. The prognostic factors
      associated with survival after treatment were analyzed. RESULTS: Six patients
      exhibited partial response to this form of HAIC (response rate=33%). The 3, 6, 9,
      12 and 18-month cumulative survival rates for the 18 patients were 83%, 72%, 50%,
      28%, and 7%, respectively. Median survival times for the six responders and 12
      non-responders were 15.0 (range, 11-18) and 7.5 (range, 1-13) months,
      respectively. It was demonstrated by both univariate and multivariate analyses
      that the therapeutic response and hepatic reserve function were significant
      prognostic factors. CONCLUSION: HAIC using low-dose cisplatin and 5-fluorouracil
      may be a useful alternative for the treatment of patients with advanced HCC
      complicated with PVTT. There may also be survival-related benefits associated
      with HAIC.

PMID- 14669310
TI  - Overexpression of HBxAg in hepatocellular carcinoma and its relationship with
      Fas/FasL system.
AB  - AIM: To study the expression and serum level of HBxAg, Fas and FasL in tissues of
      HCC patients, and to assess the relationship between HBxAg and Fas/FasL system.
      METHODS: Tissues from 50 patients with HCC were tested for the expression of
      HBxAg, Fas and FasL by S-P immunohistochemistry. Serum levels of sFas/sFasL and
      HBsAg/HBeAg were measured by ELISA assay. HBV X gene was detected by PCR in serum
      and confirmed by automatic sequencing. Fifty cases of liver cirrhosis and 30
      normal controls were involved in serum analysis. RESULTS: The expression of
      HBxAg, Fas and FasL in carcinoma tissues was 96 %, 84 % and 98 %, respectively.
      Staining of HBxAg, Fas and FasL was observed predominately in cytoplasms, no
      significant difference was found in intensity between HBxAg, Fas and FasL
      (P>0.05). HBxAg, Fas and FasL might express in the same area of carcinoma tissues
      and this co-expression could be found in most patients with HCC. The mean levels
      of sFas in serum from HCC, cirrhosis and normal controls were 762.29 +/- 391.56
      microg.L(-1), 835.36 +/- 407.33 microg.L(-1) and 238.27 +/- 135.29 microg.L(-1).
      The mean levels of sFasL in serum from HCC, cirrhosis and normal controls were
      156.36 +/- 9.61 microg.L(-1), 173.63 +/- 18.74 microg.L(-1) and 121.96 +/- 7.83
      microg.L(-1). Statistical analysis showed that both sFas and sFasL in HCC and
      cirrhosis patients were significantly higher than those in normal controls
      (P<0.01). Serum HBV X gene was found in 32% of HCC patients and 46% of cirrhotic
      patients. There was no significant relationship between serum level of sFas/sFasL
      and serum X gene detection (P>0.05). Eight percent of HCC patients with negative
      HBsAg and HBeAg in serum might have X gene in serum and HBxAg expression in
      carcinoma tissues. CONCLUSION: Our data suggest that HBxAg and Fas/FasL system
      plays an important role in the development of human HCC. Expression of HBxAg can
      leads to expression of Fas/FasL system which and reverse apoptosis of
      hepatocellular carcinoma induced by FasL.

PMID- 14669311
TI  - Combined transarterial chemoembolization and arterial administration of Bletilla
      striata in treatment of liver tumor in rats.
AB  - AIM: To evaluate and compare the effect of combined transarterial
      chemoembolization (TACE) and arterial administration of Bletilla striata (a
      Chinese traditional medicine against liver tumor) versus TACE alone for the
      treatment of hepatocellular carcinoma (HCC) in ACI rats. METHODS: Subcapsular
      implantation of a solid Morris hepatoma 3 924A (2 mm3) in the liver was carried
      out in 30 male ACI rats. Tumor volume (V1) was measured by magnetic resonance
      imaging (MRI) on day 13 after implantation. The following different agents of
      interventional treatment were injected after retrograde catheterization via
      gastroduodenal artery (on day 14), namely, (A) TACE (0.1 mg mitomycin + 0.1 ml
      Lipiodol) + Bletilla striata (1.0 mg) (n=10); (B) TACE + Bletilla striata (1.0
      mg) + ligation of hepatic artery (n=10), (C) TACE alone (control group, n=10).
      Tumor volume (V2) was assessed by MRI (on day 13 after treatment) and the tumor
      growth ratio (V2/V1) was calculated. RESULTS: The mean tumor volume before (V1)
      and after (V2) treatment was 0.0355 cm3 and 0.2248 cm3 in group A, 0.0374 cm3 and
      0.0573 cm3 in group B, 0.0380 cm3 and 0.3674 cm3 in group C, respectively. The
      mean ratio (V2/V1) was 6.2791 in group A, 1.5324 in group B and 9.1382 in group
      C. Compared with the control group (group C), group B showed significant
      inhibition of tumor growth (P<0.01), while group A did not (P>0.05). None of the
      animals died during implantation or in the postoperative period. CONCLUSION:
      Combination of TACE and arterial administration of Bletilla striata plus ligation
      of hepatic artery is more effective than TACE alone in the treatment of HCC in
      rats.

PMID- 14669312
TI  - Side effects of budesonide in liver cirrhosis due to chronic autoimmune
      hepatitis: influence of hepatic metabolism versus portosystemic shunts on a
      patient complicated with HCC.
AB  - AIM: To investigate the systemic availability of budesonide in a patient with
      Child A cirrhosis due to autoimmune hepatitis (AIH) and primary hepatocellular
      carcinoma, who developed serious side effects. METHODS: Serum levels of
      budesonide, 6beta-OH-budesonide and 16alpha-OH-prednisolone were measured by
      HPLC/MS/MS; portosystemic shunt-index (SI) was determined by 99mTc nuclear
      imaging. All values were compared with a matched control patient without side
      effects. RESULTS: Serum levels of budesonide were 13-fold increased in the index
      patient. The ratio between serum levels of the metabolites 6beta-OH-budesonide
      and 16alpha-OH-prednisolone, respectively, and serum levels of budesonide was
      diminished (1.0 vs. 4.0 for 6beta-OH-budesonide, 4.2 vs. 10.7 for 16alpha-OH
      prednisolone). Both patients had portosystemic SI (5.7% and 3.1%) within the
      range of healthy subjects. CONCLUSION: Serum levels of budesonide vary up to 13
      fold in AIH patients with Child A cirrhosis in the absence of relevant
      portosystemic shunting. Reduced hepatic metabolism, as indicated by reduced
      metabolite-to-drug ratio, rather than portosystemic shunting may explain systemic
      side effects of this drug in cirrhosis.

PMID- 14669313
TI  - Percutaneous cryoablation in combination with ethanol injection for unresectable
      hepatocellular carcinoma.
AB  - AIM: To evaluate the effectiveness and safety of percutaneous hepatic
      cryoablation in combination with percutaneous ethanol injection (PEI) in patients
      with unresectable hepatocellular carcinoma (HCC). METHODS: A total of 105 masses
      in 65 HCC patients underwent percutaneous hepatic cryoablation. The cryoablation
      was performed with the Cryocare system (Endocare, Irvine, CA, USA) using argon
      gas as a cryogen. Two freeze-thaw cycles were performed, each reaching a
      temperature of -180 degrees C at the tip of the probe. PEI was given in 36
      patients with tumor masses larger than 6 cm in diameter 1-2 weeks after
      cryoablation and then once per week for 4 to 6 sessions. The efficacy was
      evaluated with survival, change of tumor size and alpha-fetoprotein (AFP) levels.
      RESULTS: During a follow-up duration of 14 months in average with a range of 5 to
      21 months, 33 patients (50.8%) were free of tumors, 22 patients (33.8%) alive
      with tumor recurrence: two had bone metastases, three were found to have lung
      metastases, and the remaining 17 recurrences occurred in the liver, of whom only
      3 developed a cryosite recurrence. Among the 41 patients who were followed up for
      more than one year, 32(78%) were alive despite of tumor recurrence. Seven
      patients (10.8%) died due to disease recurrence. Three patients (4.6%) died due
      to some noncancer-related causes. Among the 43 patients who had a CT scan
      available for review, 38 (88.4%) had a shrinkage of tumor mass. Among the 22
      patients who received biopsies of cryoablated tumor mass, all biopsies except
      one, showed only dead or scar tissues. Of the patients who had an increased AFP
      preablatively, 91.3% had a decrease of AFP to normal or nearly normal levels
      during postablative 3-6 months. Complications of cryoablation included liver
      capsular cracking in one patient,transient thrombocytopenia in 4 patients and
      asymptomatic right-sided pleural effusions in 2 patients. Two patients developed
      liver abscess at the previous cryoablation site at 2 and 4 months, respectively,
      following cryoablation, and was recovered after treated with antibiotics and
      drainage. CONCLUSION: Percutaneous cryoablation offers a safe and possibly
      curative treatment option for patients with HCC that cannot be surgically
      removed, and its integration with PEI, may serve as an alternative to partial
      liver resection in selective patients.

PMID- 14669314
TI  - Comparative evaluation of immune response after laparoscopical and open total
      mesorectal excisions with anal sphincter preservation in patients with rectal
      cancer.
AB  - AIM: The study of immune response of open versus laparoscopical total mesorectal
      excision with anal sphincter preservation in patients with rectal cancer has not
      been reported yet. The dissected retroperitoneal area that contacts directly with
      carbon dioxide is extensive in laparoscopic total mesorectal excision with anal
      sphincter preservation surgery. It is important to clarify whether the immune
      response of laparoscopic total mesorectal excision with anal sphincter
      preservation (LTME with ASP) in patients with rectal cancer is suppressed more
      severely than that of open surgery (OTME with ASP). This study was designed to
      compare the immune functions after laparoscopic and open total mesorectal
      excision with anal sphincter preservation for rectal cancer. METHODS: This study
      involved 45 patients undergoing laparoscopic (n=20) and open (n=25) total
      mesorectal excisions with anal sphincter preservation for rectal cancer. Serum
      interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor alpha
      (TNFalpha) were assayed preoperatively and on days 1 and 5 postoperatively. CD3+
      and CD56+ T lymphocyte count, CD3- and CD56+ natural killer cell (NK) count and
      immunoglobulin (IgG/IgM/IgA) were assayed preoperatively and on day 5
      postoperatively. The numbers of CD3+ and CD56+ T lymphocytes and CD3- and CD56+
      NK cells were counted using flow cytometry. An enzyme-linked immunosorbent assay
      (ELISA) was used for IL-2, IL-6 and TNFalpha determination. And IgG, IgM, and IgA
      were assayed using immunonephelometry. RESULTS: The demographic data of the two
      groups had no difference. The preoperative levels of CD3+ and CD56+ T lymphocyte
      count, CD3- and CD56+ NK count, serum IgG, IgM, IgA, IL-2, IL-6 and TNFalpha also
      had no significant difference in the two groups (P>0.05). The CD3+ and CD56+ T
      lymphocyte counts had no obvious changes after surgery in laparoscopic (d=-0.79
      +/- 3.83%) and open (d=0.42 +/- 2.09%) groups. The CD3- and CD56+ NK counts were
      decreased postoperatively in both laparoscopic (d=-7.23 +/- 11.33%) and open (d=
      9.21 +/- 13.93%) groups. The differences of the determined values of serum IgG,
      IgM and IgA on the fifth day after operation subtracted those before operation
      were -2.56 +/- 2.14 g/L, -252.35 +/- 392.94 mg/L, -506.15 +/- 912.24 mg/L in
      laparoscopic group, and -1.81 +/- 2.10 g/L, -282.72 +/- 356.75 mg/L, -252.20 +/-
      396.28 mg/L in open group, respectively. The levels of IL-2 were decreased after
      operation in both groups. However, the levels of IL-6 were decreased after
      laparoscopic surgery (d1=-23.14 +/- 263.97 ng/L and d5=-40.08 +/- 272.03 ng/L),
      and increased after open surgery (d1=27.38 +/- 129.14 ng/L and d5=21.67 +/-
      234.31 ng/L). The TNFalpha levels were not elevated after surgery in both groups.
      There were no significant differences in the numbers of CD3+ and CD56+ T
      lymphocytes and CD3- and CD56+ NK cells, the levels of IgG, IgM, IgA, IL-2, IL-6
      and TNFalpha between the two groups (P>0.05). CONCLUSION: There are no
      differences in immune responses between the patients having laparoscopic total
      mesorectal excision with anal sphincter preservation and those undergone open
      surgery for rectal cancer.

PMID- 14669315
TI  - Hepatitis B virus genotype has no impact on hepatitis B e antigen seroconversion
      after lamivudine treatment.
AB  - AIM: To investigate the association of hepatitis B virus (HBV) genotype and HBeAg
      seroconversion after nucleotide analogue treatment. METHODS: Chronic hepatitis B
      patients receiving lamivudine followed up for at least 6 months post-treatment
      were studied. Consecutive treatment-naive patients who were prospectively
      followed up in the clinic for at least 18 months were studied as controls. HBeAg
      seroconversion was defined as loss of HBeAg, appearance of anti-HBe and
      normalization of alanine aminotransferase for at least 6 months. RESULTS: Thirty
      five patients on lamivudine and 96 control patients followed up for 39 (18-49)
      months were studied. Lamivudine was given for 12 (10-18) months, and patients
      were followed up for 15 (6-34) months after drug cessation. Genotype B and C HBV
      were found in 43 and 88 patients and HBeAg seroconversion occurred in 12 (28%)
      and 16 (18%) patients, respectively (P=0.30). There was no difference in HBeAg
      seroconversion between patients infected by genotype B and C HBV in the control
      (35% vs 21%, P=0.25) and lamivudine-treated (14% vs 10%, P=1.00) groups.
      CONCLUSION: HBeAg seroconversion after treatment by lamivudine was not influenced
      by the HBV genotype.

PMID- 14669316
TI  - N-acetyl cysteine therapy in acute viral hepatitis.
AB  - AIM: To investigate the effect of N-acetyl cysteine (NAC) on acute viral
      hepatitis (AVH). METHODS: We administered 200 mg oral NAC three times daily (600
      mg/day) to the study group and placebo capsules to the control group. All
      patients were hospitalized and diagnosed as AVH. Blood total and direct
      bilirubin, ALT, AST, alkaline phosphatase, albumin and globulin levels of each
      patient were measured twice weekly until total bilirubin level dropped under 2
      mg/dl, ALT level under 100 U/L, follow up was continued and then the patients
      were discharged. RESULTS: A total of 41(13 female and 28 male) AVH patients were
      included in our study. The period for normalization of ALT and total bilirubin in
      the study group was 19.7+/-6.9 days and 13.7 +/- 8.5 days respectively. In the
      control group it was 20.4 +/- 6.5 days and 16.9 +/- 7.8 days respectively
      (P>0.05). CONCLUSION: NAC administration effected neither the time necessary for
      normalization of ALT and total bilirubin values nor duration of hospitalization,
      so we could not suggest NAC for the treatment of icteric AVH cases. However, our
      results have shown that this drug is not harmful to patients with AVH.

PMID- 14669317
TI  - Expression of mucosal addressin cell adhesion molecule 1 on vascular endothelium
      of gastric mucosa in patients with nodular gastritis.
AB  - AIM: The interaction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1)
      with integrin alpha4beta7 mediates lymphocyte recruitment into mucosa-associated
      lymphoid tissue (MALT). Nodular gastritis is characterized by a unique military
      pattern on endoscopy representing increased numbers of lymphoid follicles with
      germinal center, strongly associated with H pylori infection. The purpose of this
      study was to address the implication of the MAdCAM-1/integrin beta7 pathway in
      NG. METHODS: We studied 17 patients with NG and H pylori infection and 19 H
      pylori-positive and 14 H pylori-negative controls. A biopsy sample was taken from
      the antrum and snap-frozen for immunohistochemical analysis of MAdCAM-1 and
      integrin beta7. In simultaneous viewing of serial sections, the percentage of
      MAdCAM-1-positive to von Willebrand factor-positive vessels was calculated. We
      also performed immunostaining with anti-CD20, CD4, CD8 and CD68 antibodies to
      determine the lymphocyte subsets co-expressing integrin beta7. RESULTS: Vascular
      endothelial MAdCAM-1 expression was more enhanced in gastric mucosa with than
      without H pylori infection. Of note, the percentages of MAdCAM-1-positive vessels
      were significantly higher in the lamina propria of NG patients than in H pylori
      positive controls. Strong expression of MAdCAM-1 was identified adjacent to
      lymphoid follicles and dense lymphoid aggregates. Integrin beta7-expressing
      mononuclear cells, mainly composed of CD20 and CD4 lymphocytes, were associated
      with vessels lined with MAdCAM-1-expressing endothelium. CONCLUSION: Our results
      suggest that the MAdCAM-1/integrin alpha4beta7 homing system may participate in
      gastric inflammation in response to H pylori-infection and contributes to MALT
      formation, typically leading to the development of NG.

PMID- 14669318
TI  - Epithelial cell proliferation and glandular atrophy in lymphocytic gastritis:
      effect of H pylori treatment.
AB  - AIM: Lymphocytic gastritis is commonly associated with Helicobacter pylori
      infection. The presence of glandular atrophy and foveolar hyperplasia in
      lymphocytic gastritis suggests abnormalities in cell proliferation and
      differentiation, forming a potential link with the suspected association with
      gastric cancer. Our aim was to compare epithelial cell proliferation and
      morphology in H pylori associated lymphocytic gastritis and H pylori gastritis
      without features of lymphocytic gastritis, and to evaluate the effect of H pylori
      treatment. METHODS: We studied 14 lymphocytic gastritis patients with H pylori
      infection. For controls, we selected 14 matched dyspeptic patients participating
      in another treatment trial whose H pylori infection had successfully been
      eradicated. Both groups were treated with a triple therapy and followed up with
      biopsies for 6-18 months (patients) or 3 months (controls). Blinded evaluation
      for histopathological features was carried out. To determine the cell
      proliferation index, the sections were labeled with Ki-67 antibody. RESULTS:
      Before treatment, lymphocytic gastritis was characterized by foveolar hyperplasia
      (P=0.001) and glandular atrophy in the body (P=0.008), and increased
      proliferation in both the body (P=0.001) and antrum (P=0.002). Proliferation
      correlated with foveolar hyperplasia and inflammation activity. After eradication
      therapy, the number of intraepithelial lymphocytes decreased in the body
      (P=0.004) and antrum (P=0.065), remaining higher than in controls (P<0.001).
      Simultaneously, the proliferation index decreased in the body from 0.38 to 0.15
      (P=0.043), and in the antrum from 0.34 to 0.20 (P=0.069), the antral index still
      being higher in lymphocytic gastritis than in controls (P=0.010). Foveolar
      hyperplasia and glandular atrophy in the body improved (P=0.021), reaching the
      non-LG level. CONCLUSION: In lymphocytic gastritis, excessive epithelial cell
      proliferation is predominantly present in the body, where it associates with
      foveolar hyperplasia and glandular atrophy. These characteristic changes of
      lymphocytic gastritis are largely related to H pylori infection, as shown by
      their improvement after eradication. However, some residual deviation was still
      seen in lymphocytic gastritis, indicating either an abnormally slow improvement
      or the presence of some persistent abnormality.

PMID- 14669319
TI  - Expression of Helicobacter pylori Hsp60 protein and its immunogenicity.
AB  - AIM: To express Hsp60 protein of H pylori by a constructed vector and to evaluate
      its immunogenicity. METHODS: Hsp60 DNA was amplified by PCR and inserted into the
      prokaryote expression vector pET-22b (+), which was transformed into BL21 (DE3)
      E.coli strain to express recombinant protein. Immunogenicity of expressed Hsp60
      protein was evaluated with animal experiments. RESULTS: DNA sequence analysis
      showed Hsp60 DNA was the same as GenBank's research. Hsp60 recombinant protein
      accounted for 27.2% of the total bacterial protein, and could be recognized by
      the serum from H pylori infected patients and Balb/c mice immunized with Hsp60
      itself. CONCLUSION: Hsp60 recombinant protein might become a potential vaccine
      for controlling and treating H pylori infection.

PMID- 14669320
TI  - Distribution and expression of non-muscle myosin light chain kinase in rabbit
      livers.
AB  - AIM: To study the distribution and expression of non-muscle myosin light chain
      kinase (nmMLCK) in rabbit livers. METHODS: Human nmMLCK N-terminal cDNA was
      amplified by polymerase chain reaction (PCR) and was inserted into pBKcmv to
      construct expression vectors. The recombinant plasmid was transformed into XL1
      blue. Expression protein was induced by IPTG and then purified by SDS-PAGE and
      electroelution, which was used to prepare the polycolonal antibody to detect the
      distribution and expression of nmMLCK in rabbit livers with immunofluorescene
      techniques. RESULTS: The polyclonal antibody was prepared, by which nmMLCK
      expression was detected and distributed mainly in peripheral hepatocytes.
      CONCLUSION: nmMLCK can express in hepatocytes peripherally, and may play certain
      roles in the regulation of hepatic functions.

PMID- 14669321
TI  - Identification of alkA gene related to virulence of Shigella flexneri 2a by
      mutational analysis.
AB  - AIM: In vivo induced genes are thought to play an important role during infection
      of host. AlkA was identified as an in vivo-induced gene by in vivo expression
      technology (IVET), but its virulence in Shigella flexneri was not reported. The
      purpose of this study was to identify the role of alkA gene in the pathogenesis
      of S. flexneri. METHODS: PCR was used to amplify alkA gene of S. flexneri 2a and
      fragment 028pKm. The fragment was then transformed into 2457T05 strain, a S
      flexneri 2a strain containing Red recombination system, which was constructed
      with a recombinant suicide plasmid pXLkd46. By in vivo homologous recombination,
      alkA mutants were obtained and verified by PCR and sequencing. Intracellular
      survival assay and virulence assay were used to test the intracellular survival
      ability in HeLa cell model and the virulence in mice lung infection model
      respectively. RESULTS: Deletion mutant of S. flexneri 2a alkA was successfully
      constructed by gamma Red recombination system. The mutant exhibited significant
      survival defects and much significant virulence defects in mice infection assay.
      CONCLUSION: AlkA gene plays an important role in the infection of epithelial
      cells and is a virulent gene of Shigella spp.

PMID- 14669322
TI  - Differentially expressed proteins of gamma-ray irradiated mouse intestinal
      epithelial cells by two-dimensional electrophoresis and MALDI-TOF mass
      spectrometry.
AB  - AIM: To identify the differentially expressed proteins involved in ionizing
      radiation in mice and to explore new ways for studying radiation-related
      proteins. METHODS: Bal B/c mice grouped as sham-irradiation, 3 h and 72 h
      irradiation were exposed to 9.0 Gy single dose of gamma-irradiation. Intestinal
      epithelia were isolated from mice, and total proteins were extracted with urea
      containing solution. A series of methods were used, including two-dimensional
      electrophoresis, PDQuest 2-DE software analysis, peptide mass fingerprinting
      based on matrix-assisted laser desorption/ionization time of flight mass
      spectrometry (MALDI-TOF-MS) and SWISS-PROT database searching, to separate and
      identify the differential proteins. Western blotting and RT-PCR were used to
      validate the differentially expressed proteins. RESULTS: Mouse intestine was
      severely damaged by 9.0 Gy gamma-irradiation. Image analysis of two-dimensional
      gels revealed that averages of 638 +/- 39, 566 +/- 32 and 591 +/- 29 protein
      spots were detected in 3 groups, respectively, and the majority of these protein
      spots were matched. About 360 protein spots were matched between normal group and
      3 h irradiation group, and the correlation coefficient was 0.78 by correlation
      analysis of gels. Also 312 protein spots matched between normal group and 72 h
      irradiation group, and 282 protein spots between 3 h and 72 h irradiation groups.
      Twenty-eight differential protein spots were isolated from gels, digested with
      trypsin, and measured with MALDI-TOF-MS. A total of 25 spots yielded good
      spectra, and 19 spots matched known proteins after database searching. These
      proteins were mainly involved in anti-oxidation, metabolism, signal transduction,
      and protein post-translational processes. Western-blotting confirmed that enolase
      was up-regulated by gamma-irradiation. Up-regulation of peroxiredoxin I was
      verified by applying RT-PCR technique, but no change occurred in Q8VC72.
      CONCLUSION: These differentially expressed proteins might play important roles
      when mouse intestine was severely injured by gamma-irradiation. It is suggested
      that differential proteomic analysis may be a useful tool to study the proteins
      involved in radiation damage of mouse intestinal epithelia.

PMID- 14669323
TI  - Heterologous expression of human cytochrome P450 2E1 in HepG2 cell line.
AB  - AIM: Human cytochrome P-450 2E1 (CYP2E1) takes part in the biotransformation of
      ethanol, acetone, many small-molecule substrates and volatile anesthetics. CYP2E1
      is involved in chemical activation of many carcinogens, procarcinogens, and
      toxicants. To assess the metabolic and toxicological characteristics of CYP2E1,
      we cloned CYP2E1 cDNA and established a HepG2 cell line stably expressing
      recombinant CYP 2E1. METHODS: Human CYP2E1 cDNA was amplified with reverse
      transcription-polymerase chain reaction (RT-PCR) from total RNAs extracted from
      human liver and cloned into pGEM-T vector. The cDNA segment was identified by DNA
      sequencing and subcloned into a mammalian expression vector pREP9. A transgenic
      cell line was established by transfecting the recombinant plasmid of pREP9-CYP2E1
      to HepG2 cells. The expression of CYP2E1 mRNA was validated by RT-PCR. The enzyme
      activity of CYP2E1 catalyzing oxidation of 4-nitrophenol in postmitochondrial
      supernate (S9) fraction of the cells was determined by spectrophotometry. The
      metabolic activation of HepG2-CYP2E1 cells was assayed by N-nitrosodiethylamine
      (NDEA) cytotoxicity and micronucleus test. RESULTS: The cloned CYP2E1 cDNA
      segment was identical to that reported by Umeno et al (GenBank access No.
      J02843). HepG2-CYP2E1 cells expressed CYP2E1 mRNA and had 4-nitrophenol
      hydroxylase activity (0.162 +/- 0.025 nmol.min(-1).mg(-1) S9 protein), which were
      undetectable in parent HepG2 cells. HepG2-CYP2E1 cells increased the cytotoxicity
      and micronucleus rate of NDEA in comparison with those of HepG2 cells.
      CONCLUSION: The cDNA of human CYP2E1 can be successfully cloned, and a cell line,
      HepG2-CYP2E1, which can efficiently express mRNA and has CYP2E1 activity, is
      established. The cell line is useful for testing the cytotoxicity, mutagenicity
      and metabolism of xenobiotics, which may possibly be activated or metabolized by
      CYP2E1.

PMID- 14669324
TI  - Hepatocellular apoptosis after hepatectomy in obstructive jaundice in rats.
AB  - AIM: To investigate the hepatocellular apoptosis after hepatectomy in obstructive
      jaundice and biliary decompression rats. METHODS: After bile duct ligation for 7
      days, rats were randomly divided into OB group in which the rats underwent 70%
      hepatectomy, OB-CD group in which the rats underwent hepatectomy accompanied by
      choledochoduodenostomy, CD-Hx group in which the rats underwent
      choledochoduodenostomy and then received 70% hepatectomy on the fifth day after
      biliary decompression. The control group (Hx group) only underwent hepatectomy.
      RESULTS: The level of total serum bilirubin and serum enzymes was significantly
      lower in CD-Hx group than in OB-CD and OB groups on day 1, 3 and 5 after
      hepatectomy. The apoptotic index was significantly lower in CD-Hx group than in
      OB-CD and OB groups on day 3 and 5. The oligonucleosomal DNA fragments and
      Caspase-3 activity were also lower in CD-Hx group than in OB-CD and OB groups 3
      days after hepatectomy, without differences between CD-Hx and Hx groups.
      CONCLUSION: Hepatocellular apoptosis plays vital roles in jaundice rats, and
      biliary decompression is more effective in treatment of patients with severe
      jaundice before operation.

PMID- 14669325
TI  - Effects of long-term tea polyphenols consumption on hepatic microsomal drug
      metabolizing enzymes and liver function in Wistar rats.
AB  - AIM: To investigate the effects of long-term tea polyphenols (TPs) consumption on
      hepatic microsomal drug-metabolizing enzymes and liver function in rats. METHODS:
      TPs were administered intragastrically to rats at the doses of 833 mg.kg(-1).d(
      1) (n=20) and 83.3 mg.kg(-1).d(-1) (n=20) respectively for six months. Controlled
      group (n=20) was given same volume of saline solution. Then the contents of
      cytochrome P450, b5, enzyme activities of aminopyrine N-demethylase (ADM),
      glutathione S-transferase (GST) and the biochemical liver function of serum were
      determined. RESULTS: The contents of cytochrome P450 and b5 in the livers of male
      rats in high dose groups (respectively 2.66 +/- 0.55, 10.43 +/- 2.78 nmol.mg MS
      pro(-1)) were significantly increased compared with the control group (1.08 +/-
      1.04, 5.51 +/- 2.98 nmol.mg MS pro(-1); P<0.01, respectively). The enzymatic
      activities of ADM in the livers of female rats in high dose groups (0.91 +/- 0.08
      mmol.mg MS pro(-1)min(-1)) were increased compared with the control group (0.82
      +/- 0.08 mmol.mg MS pro(-1).min(-1); P<0.05). The GST activity was unchanged in
      all treated groups, and the function of liver was not obviously changed.
      CONCLUSION: The antidotal capability of rats' livers can be significantly
      improved after long-term consumption of TPs. There are differences in changes of
      drug-metabolizing enzymes between the sexes induced by TPs and normal condition.

PMID- 14669327
TI  - Establishment and characterization of a rat pancreatic stellate cell line by
      spontaneous immortalization.
AB  - AIM: Activated pancreatic stellate cells (PSCs) have been implicated in the
      pathogenesis of pancreatic fibrosis and inflammation. Primary PSCs can be
      subcultured only several times because of their limited growth potential. A
      continuous cell line may therefore be valuable in studying molecular mechanisms
      of these pancreatic disorders. The aim of this study was to establish a cell line
      of rat PSCs by spontaneous immortalization. METHODS: PSCs were isolated from the
      pancreas of male Wistar rats, and conventional subcultivation was performed
      repeatedly. Telomerase activity was measured using the telomere repeat
      amplification protocol. Activation of transcription factors was assessed by
      electrophoretic mobility shift assay. Activation of mitogen-activated protein
      (MAP) kinases was examined by Western blotting using anti-phosphospecific
      antibodies. Expression of cytokine-induced neutrophil chemoattractant-1 was
      determined by enzyme immunoassay. RESULTS: Conventional subcultivation yielded
      actively growing cells. One clone was obtained after limiting dilution, and
      designated as SIPS. This cell line has been passaged repeatedly more than 2
      years, and is thus likely immortalized. SIPS cells retained morphological
      characteristics of primary, culture-activated PSCs. SIPS expressed alpha-smooth
      muscle actin, glial acidic fibrillary protein, vimentin, desmin, type I collagen,
      fibronectin, and prolyl hydroxylases. Telomerase activity and p53 expression were
      negative. Proliferation of SIPS cells was serum-dependent, and stimulated with
      platelet-derived growth factor-BB through the activation of extracellular signal
      regulated kinase. Interleukin-1beta activated nuclear factor-kappaB, activator
      protein-1, and MAP kinases. Interleukin-1beta induced cytokine-induced neutrophil
      chemoattractant-1 expression through the activation of nuclear factor-kappaB and
      MAP kinases. CONCLUSION: SIPS cells can be useful for in vitro studies of cell
      biology and signal transduction of PSCs.

PMID- 14669326
TI  - Oil A induces apoptosis of pancreatic cancer cells via caspase activation,
      redistribution of cell cycle and GADD expression.
AB  - AIM: To explore the mechanisms of effects of oil A on apoptosis of human
      pancreatic cancer cells. METHODS: Cellular DNA content was analyzed by flow
      cytometry. Western blotting was used for caspase-3 and PARP, caspase-7, caspase
      9, cytochrome c, Bcl-2, Bax, Mcl-1, cyclinA, cyclin B1, cyclin D1, cyclin E,
      CDK2, CDK4, CDK6, P21, P27, GADD45, GADD153. RESULTS: The caspase-3, caspase-7,
      and caspase-9 activities were significantly increased as well as the cleavage of
      caspase-3, downstream substrate poly-ADP ribose polymerase (PARP) was induced.
      The amount of cytochrome c in the cytosolic fraction was increased, while the
      amount of cytochrome c in the mitochondrial fraction was decreased after oil A
      treatment. The anti-apoptosis proteins Bcl-2 and Mcl-1 were decreased in parallel
      and Bax increased, indicating that Bcl-2 family proteins-mitochondria-caspase
      cascade was responsible for oil-induced apoptosis. The proportion of cells in the
      G0/G1 decreased in MiaPaCa-2 and AsPC-1 cells after the treatment of oil A for 24
      hours. The number of cells in S phase was increased in two cancer cell lines at
      24 hours. Therefore, cells were significantly accumulated in G2/M phase. The
      cells with a sub-G0/G1 DNA content, a hallmark of apoptosis, were seen at 24
      hours both in MiaPaCa-2 and AsPC-1 cells following exposure to oil A. The
      expression of cyclin A and cyclin B1 was slightly decreased and cyclin D1 levels
      were markedly lowered in MiaPaCa-2 cells. The expression of cyclin A and cyclin
      B1 was markedly decreased and cyclin D1 levels were slightly lowered in AsPC-1
      cells, while cyclin E was not affected and the levels of CDK2, CDK4, and CDK6
      were unchanged in MiaPaCa-2 and AsPC-1 cells. In response to oil A, P21
      expression was increased, but P27 expression was not affected. The expression of
      both GADD45 and GADD153 was increased in two cell lines following oil A
      treatment. CONCLUSION: Oil A induces apoptosis of pancreatic cancer cells via
      activating caspase cascade, modifying cell cycle progress and changing cell cycle
      regulating proteins and GADD expression.

PMID- 14669328
TI  - Effects of bile acids on proliferation and ultrastructural alteration of
      pancreatic cancer cell lines.
AB  - AIM: Pancreatic cancer in the head is frequently accompanied by jaundice and high
      bile acid level in serum. This study focused on the direct effects of bile acids
      on proliferation and ultrastructural alteration of pancreatic cancer. METHODS:
      Pancreatic cancer cell lines PANC-1, MIA PaCa-2 and PGHAM-1 were explored in this
      study. The cell lines were cultured in media supplemented with certain bile
      acids, CA, DCA, LCA, TCDC, TDCA and GCA. Their influence on cell growth was
      measured with MTT assay after 72 h of incubation. Cell cycles of PANC-1 cells in
      40 microM of bile acids media were analyzed by flow cytometry. Ultrastructural
      alteration of PANC-1 cells induced by DCA was observed using scanning and
      transmission electron microscope (SEM and TEM). RESULTS: At various
      concentrations of bile acids and incubation time, no enhanced effects of bile
      acids on cell proliferation were observed. Significant inhibitory effects were
      obtained in almost all media with bile acids. DCA and CA increased the percentage
      of G0+G1 phase cells, while GCA and TDCA elevated the S phase cell number. After
      48 h of incubation in DCA medium, PANC-1 cells showed some structural damages
      such as loss of their microvilli and vacuolization of organelles in cytoplasm.
      CONCLUSION: Bile acids can reduce proliferation of pancreatic cancer cells due to
      their direct cytotoxicity. This result implies that elevation of bile acids in
      jaundiced serum may inhibit pancreatic cancer progression.

PMID- 14669329
TI  - Loss of DPC4 expression and its correlation with clinicopathological parameters
      in pancreatic carcinoma.
AB  - AIM: DPC4 is a tumor suppressor gene on chromosome 18q21.1 that has high mutant
      frequencies in pancreatic carcinogenesis. The purpose of this study was to
      investigate the role of DPC4 alterations in tumorigenesis and progression of
      pancreatic carcinomas. METHODS: We studied the immunohistochemical markers of
      DPC4 in 34 adenocarcinomas and 16 nonmalignant specimens from the pancreas. The
      16 nonmalignant specimens from the pancreas included 8 non-neoplastic cysts and 8
      normal pancreatic tissues. The relationship between DPC4 alterations and various
      clinicopathological parameters was evaluated by chi-square test or Fisher's exact
      test. Survivals were calculated using Kaplan-Meier method (by a log-rank test).
      RESULTS: All the 16 nonmalignant cases of the pancreas showed expression of DPC4
      gene. Loss of DPC4 expression was seen in 8 of 34(23.5%) pancreatic
      adenocarcinomas. The frequency of loss of DPC4 expression was higher in poorly
      differentiated adenocarcinoma (G3) than in well and moderately differentiated
      adenocarcinoma (G1 and G2) histologically (P=0.037). Loss of DPC4 expression of
      the patients at TNM stage IV was also higher than that of the patients at TNM
      stages I, II and III (60.0% at stage IV, versus 14.3% at stage I, 18.2% at stage
      II, and 18.2% at stage III) (P=0.223). The mean and median survival in patients
      with DPC4 expression was longer than those in patients with loss of DPC4
      expression. Kaplan-Meier survival analysis demonstrated patients with DPC4
      expression had a higher survival rate than patients with loss of DPC4 expression,
      but the difference did not reach statistical significance (P=0.879). CONCLUSION:
      This study suggests that DPC4 is involved in the development of pancreatic
      carcinoma and is a late event in pancreatic carcinogenesis, DPC4 expression may
      be a molecular prognostic marker for pancreatic carcinoma.

PMID- 14669330
TI  - G and D cells in rat antral mucosa: an immunoelectron microscopic study.
AB  - AIM: To investigate the gastrin secreting cells (G cells) and the somatostatin
      secreting cells (D cells) of antral mucosa in rats at the ultrastructural level.
      METHODS: Revised immunoelectron microscopic technique was used to detect the G
      cells and D cells in rat antral mucosa through gastrin and somatostatin
      antibodies labeled by colloidal gold. Also the relevant quantitative analysis
      regarding the granular number of colloidal gold in G cells and in D cells was
      conducted. RESULTS: Immunological granules of colloidal gold were distributed in
      G cells and D cells. Gastrin labeled golden granules or somatostatin labeled ones
      presented mainly as lobation-like or island-like congeries. Most of the golden
      congeries were observed dissociated in cytoplasms of G cells or D cells, near the
      basement membrane. A few golden congeries were located in nuclei. The number of
      golden granules in one G cell was around 107.04 +/- 19.68 and was 83.36 +/- 17.58
      in one D cell. CONCLUSION: Gastrin secreting granules are located in cytoplasms
      and nuclei of G cells, and somatostatin secreting granules both in cytoplasms and
      in nuclei of D cells. The number of golden granules can be quantitatively
      analyzed to determine the relative amount of gastrin secreting granules or
      somatostatin secreting granules.

PMID- 14669331
TI  - Effect of complex amino acid imbalance on growth of tumor in tumor-bearing rats.
AB  - AIM: To investigate the effect of complex amino acid imbalance on the growth of
      tumor in tumor-bearing (TB) rats. METHODS: Sprague-Dawley (SD) rats underwent
      jejunostomy for nutritional support. A suspension of Walker-256 carcinosarcoma
      cells was subcutaneously inoculated. TB rats were randomly divided into groups A,
      B, C and D according to the formula of amino acids in enteral nutritional
      solutions, respectively. TB rats received jejunal feedings supplemented with
      balanced amino acids (group A), methionine-depleted amino acids (group B), valine
      depleted amino acids (group C) and methionine- and valine-depleted complex amino
      acid imbalance (group D) for 10 days. Tumor volume, inhibitory rates of tumor,
      cell cycle and life span of TB rats were investigated. RESULTS: The G0/G1 ratio
      of tumor cells in group D (80.5 +/- 9.0)% was higher than that in groups A, B and
      C which was 67.0 +/- 5.1%, 78.9 +/- 8.5%, 69.2 +/- 6.2%, respectively (P<0.05).
      The ratio of S/G2M and PI in group D were lower than those in groups A, B and C.
      The inhibitory rate of tumor in groups B, C and D was 37.2%, 33.3% and 43.9%,
      respectively (P<0.05). The life span of TB rats in group D was significantly
      longer than that in groups B, C, and A. CONCLUSION: Methionine/valine-depleted
      amino acid imbalance can inhibit tumor growth. Complex amino acids of methionine
      and valine depleted imbalance have stronger inhibitory effects on tumor growth.

PMID- 14669332
TI  - Alterations of intestinal mucosa structure and barrier function following
      traumatic brain injury in rats.
AB  - AIM: Gastrointestinal dysfunction is a common complication in patients with
      traumatic brain injury (TBI). However, the effect of traumatic brain injury on
      intestinal mucosa has not been studied previously. The aim of the current study
      was to explore the alterations of intestinal mucosa morphology and barrier
      function, and to determine how rapidly the impairment of gut barrier function
      occurs and how long it persists following traumatic brain injury. METHODS: Male
      Wistar rats were randomly divided into six groups (6 rats each group) including
      controls without brain injury and traumatic brain injury groups at hours 3, 12,
      24, and 72, and on day 7. The intestinal mucosa structure was detected by
      histopathological examination and electron microscopy. Gut barrier dysfunction
      was evaluated by detecting serum endotoxin and intestinal permeability. The level
      of serum endotoxin and intestinal permeability was measured by using chromogenic
      limulus amebocyte lysate and lactulose/mannitol (L/M) ratio, respectively.
      RESULTS: After traumatic brain injury, the histopathological alterations of gut
      mucosa occurred rapidly as early as 3 hours and progressed to a serious state,
      including shedding of epithelial cells, fracture of villi, focal ulcer, fusion of
      adjacent villi, dilation of central chyle duct, mucosal atrophy, and vascular
      dilation, congestion and edema in the villous interstitium and lamina propria.
      Apoptosis of epithelial cells, fracture and sparseness of microvilli, loss of
      tight junction between enterocytes, damage of mitochondria and endoplasm, were
      found by electron microscopy. The villous height, crypt depth and surface area in
      jejunum decreased progressively with the time of brain injury. As compared with
      that of control group (183.7 +/- 41.8 EU/L), serum endotoxin level was
      significantly increased at 3, 12, and 24 hours following TBI (434.8 +/- 54.9
      EU/L, 324.2 +/- 61.7 EU/L and 303.3 +/- 60.2 EU/L, respectively), and peaked at
      72 hours (560.5 +/- 76.2 EU/L), then declined on day 7 (306.7 +/- 62.4 EU/L,
      P<0.01). Two peaks of serum endotoxin level were found at hours 3 and 72
      following TBI. L/M ratio was also significantly higher in TBI groups than that in
      control group (control, 0.0172 +/- 0.0009; 12 h, 0.0303 +/- 0.0013; 24 h, 0.0354
      +/- 0.0025; 72 h, 0.0736 +/- 0.0105; 7 d, 0.0588 +/- 0.0083; P<0.01). CONCLUSION:
      Traumatic brain injury can induce significant damages of gut structure and
      impairment of barrier function which occur rapidly as early as 3 hours following
      brain injury and lasts for more than 7 days with marked mucosal atrophy.

PMID- 14669333
TI  - Changes of biological functions of dipeptide transporter (PepT1) and hormonal
      regulation in severe scald rats.
AB  - AIM: To determine the regulatory effects of recombinant human growth hormone
      (rhGH) on dipeptide transport (PepT1) in normal and severe scald rats. METHODS:
      Male Sprague-Dawley rats with 30% total body surface area (TBSA) III degree scald
      were employed as the model. In this study rhGH was used at the dose of 2 IU/kg(
      1)d(-1). An everted sleeve of intestine 4 cm long obtained from mid-jejunum was
      securely incubated in Kreb's solution with radioactive dipeptide (3H
      glycylsarcosine, 3H-Gly-Sar, 10 microCi/ml) at 37 degrees C for 15 min to measure
      the effects of uptake and transport of PepT1 of small intestinal epithelial cells
      in normal and severe scald rats. RESULTS: Abundant blood supply to intestine and
      mesentery was observed in normal and scald rats administered rhGH, while less
      supply of blood to intestine and mesentery was observed in rats without rhGH.
      Compared with controls, the transport of dipeptide in normal rats with injection
      of rhGH was not significantly increased (P=0.1926), while the uptake was
      significantly increased (P=0.0253). The effects of transport and uptake of PepT1
      in scald rats with injection of rhGH were significantly increased (P=0.0082,
      0.0391). CONCLUSION: Blood supply to intestine and mesentery of rats was
      increased following injection of rhGH. The effects of uptake and transport of
      dipeptide transporters in small intestinal epithelial cells of rats with severe
      scald were markedly up-regulated by rhGH.

PMID- 14669334
TI  - Protective effect of angelica sinensis polysaccharide on experimental
      immunological colon injury in rats.
AB  - AIM: To study the effect of angelica sinensis polysaccharide (ASP) on
      immunological colon injury and its mechanisms in rats. METHODS: Immunological
      colitis model of rats was induced by intracolon enema with 2, 4, 6
      trinitrobenzene sulfonic acid (TNBS) and ethanol. The experimental animals were
      randomly divided into normal control, model control, 5-aminosalicylic acid
      therapy groups and three doses of ASP therapy groups. The 6 groups were treated
      intracolonically with normal saline, normal saline, 5-aminosalicylic acid (100
      mg.kg(-1)), and ASP daily (8:00 am) at the doses of 200, 400 and 800 mg.kg(-1)
      respectively for 21 days 7 d following induction of colitis. The rat colon mucosa
      damage index (CMDI), the histopathological score (HS), the score of occult blood
      test (OBT), and the colonic MPO activity were evaluated. The levels of SOD, MDA,
      NO, TNF-alpha, IL-2 and IL-10 in colonic tissues were detected biochemically and
      immunoradiometrically. The expressions of TGF-beta and EGF in colonic tissues
      were also determined immunochemically. RESULTS: Enhanced colonic mucosal injury,
      inflammatory response and oxidative stress were observed in colitis rats, which
      manifested as significant increases of CMDI, HS, OBT, MPO activity, MDA and NO
      contents, as well as the levels of TNF-alpha and IL-2 in colonic tissues,
      although colonic TGF-beta protein expression, SOD activity and IL-10 content were
      significantly decreased compared with the normal control (P<0.01). However, these
      parameters were found to be significantly ameliorated in colitis rats treated
      intracolonically with ASP at the doses of 400 and 800 mg.kg(-1) (P<0.05-0.01).
      Meantime, colonic EGF protein expression in colitis rats was remarkably up
      regulated. CONCLUSION: ASP has a protective effect on immunological colon injury
      induced by TNBS and ethanol enema in rats, which was probably due to the
      mechanism of antioxidation, immunomodulation and promotion of wound repair.

PMID- 14669335
TI  - Visceral hypersensitivity and altered colonic motility after subsidence of
      inflammation in a rat model of colitis.
AB  - AIM: Irritable bowel syndrome (IBS) is a functional bowel disorder characterized
      by visceral hypersensitivity and altered bowel motility. There is increasing
      evidence suggesting the role of inflammation in the pathogenesis of IBS, which
      addresses the possibility that formerly established rat model of colitis could be
      used as an IBS model after the inflammation subsided. METHODS: Colitis was
      induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley
      rats. The extent of inflammation was assessed by histological examination and
      myeloperoxidase (MPO) activity assay. After subsidence of colitis, the rats were
      subjected to rectal distension and restraint stress, then the abdominal
      withdrawal reflex and the number of stress-induced fecal output were measured,
      respectively. RESULTS: At 2 days post-induction of colitis, the colon showed
      characteristic inflammatory changes in histology and 8-fold increase in MPO
      activity. At 7 days post-induction of colitis, the histological features and MPO
      activity returned to normal. The rats at 7 days post-induction of colitis showed
      hypersensitive response to rectal distension without an accompanying change in
      rectal compliance, and defecated more stools than control animals when under
      stress. CONCLUSION: These results concur largely with the characteristic features
      of IBS, visceral hypersensitivity and altered defecation pattern in the absence
      of detectable disease, suggesting that this animal model is a methodologically
      convenient and useful model for studying a subset of IBS.

PMID- 14669336
TI  - Relationship between clinical and pathologic findings in patients with chronic
      liver diseases.
AB  - AIM: To explore the relationship between clinical findings of patients with
      chronic liver diseases and the pathologic grading and staging of liver tissues.
      METHODS: The inflammatory activity and fibrosis of consecutive liver biopsies
      from 200 patients were determined according to the diagnosis criteria of chronic
      hepatitis in China established in 1995. A comparative analysis was carried out
      for 200 patients with chronic liver diseases by comparing their clinical
      manifestations, serum biochemical markers with the grading and staging of liver
      tissues. RESULTS: It was revealed that age, index of clinical symptoms and
      physical signs were obviously relevant to the pathologic grading and staging of
      liver tissues (P<0.05). Blood platelet, red blood cells, aspartate
      aminotransferase (AST), N-terminal procollagen III (PIII NP) were apparently
      correlated with the degree of inflammation. PGA (prothrombin time, GGT,
      apoprotein A1) index, PGAA (PGA+delta2-macroglobulin) index, albumin and
      albumin/globulin were relevant to both inflammation and fibrosis. Hyaluronic acid
      (HA) was an accurate variable for the severity of hepatic inflammation and
      fibrosis. The combination of serum markers for fibrosis could increase the
      diagnostic accuracy. It was notable that viral replication markers were not
      relevant to the degree of inflammation and fibrosis. CONCLUSION: There is a good
      correlation between clinical findings and the pathologic grading and staging of
      liver tissues, which may give aid to the noninvasive diagnosis of liver fibrosis.

PMID- 14669337
TI  - Impact of endoscopically minimal involvement on IL-8 mRNA expression in
      esophageal mucosa of patients with non-erosive reflux disease.
AB  - AIM: Little has been known about the pathogenesis of non-erosive reflux disease
      (NERD). Recent studies have implicated interleukin 8 (IL-8) in the development
      and progression of gastroesophogeal reflux disease (GERD). The purpose of this
      study was to determine IL-8 RNA expression levels in NERD patients with or
      without subtle mucosal changes. METHODS: We studied 26 patients with NERD and 13
      asymptomatic controls. Biopsy sample was taken from the esophagus 3 cm above the
      gastroesophageal junction and snap frozen for measurement of IL-8 mRNA levels by
      real-time quantitative polymerase chain reaction (PCR). We also examined mRNA
      expression of IL-8 receptors, CXCR-1 and -2 by reverse transcriptase PCR. The
      patients were endoscopically classified into grade M (mucosal color changes
      without visible mucosal break) and N (neither minimal involvement nor mucosal
      break) of the modified Los Angeles classification. RESULTS: The relative IL-8
      mRNA expression levels were significantly higher in esophageal mucosa of NERD
      patients than those in esophageal mucosa of the controls. There was a significant
      difference in IL-8 mRNA levels between grades M and N. The CXCR-1 and -2 mRNAs
      were constitutively expressed in esophageal mucosa. CONCLUSION: Our results
      suggest that high IL-8 levels in esophageal mucosa may be involved in the
      pathogenesis of NERD through interaction with its receptors. NERD seems to be
      composed of a heterogeneous population in terms of not only endoscopically
      minimal involvement but also immune and inflammatory processes.

PMID- 14669338
TI  - Endoscopic banding ligation can effectively resect hyperplastic polyps of
      stomach.
AB  - AIM: Bleeding and perforation are the major and serious complications associated
      with endoscopic polypectomy. To develop a safe and effective method to resect
      hyperplastic polyps of the stomach, we employed rubber bands to strangulate
      hyperplastic polyps and to determine the possibility of inducing avascular
      necrosis in these lesions. METHODS: Forty-seven patients with 72 hyperplastic
      polyps were treated with endoscopic banding ligation (EBL). On 14 days after
      endoscopic ligation, follow-up endoscopies were performed to assess the outcomes
      of the strangulated polyps. RESULTS: After being strangulated by the rubber
      bands, all of the polyps immediately became congested (100%), and then developed
      cyanotic changes (100%) approximately 4 minutes later. On follow-up endoscopy 2
      weeks later, all the polyps except one had dropped off. The only one residual
      polyp shrank with a rubber band in its base, and it also dropped off
      spontaneously during subsequent follow-up. No complications occurred during or
      following the ligation procedures. CONCLUSION: Gastric polyps develop avascular
      necrosis following ligation by rubber bands. Employing suction equipment, EBL can
      easily capture sessile polyps. It is an easy, safe and effective method to
      eradicate hyperplastic polyps of the stomach.

PMID- 14669339
TI  - Clinical manifestations and prognostic factors in patients with gastrointestinal
      stromal tumors.
AB  - AIM: To investigate the incidence of CD117-positive immunohistochemical staining
      in previously diagnosed gastrointestinal (GI) tract stromal tumors (GIST) and to
      analyze the tumors' clinical manifestations and prognostic factors. METHODS: We
      retrospectively reviewed 91 cases with a previous diagnosis of GI stromal tumor,
      leiomyoma, or leiomyosarcoma. Tissue samples were assessed with CD117, CD34, SMA
      and S100 immunohistochemical staining. Clinical and pathological characteristics
      were analyzed for prognostic factors. RESULTS: CD117 was positive in 81 (89%) of
      91 tissue samples. There were 59 cases (72.8%) positive for CD34, 13 (16%)
      positive for SMA, and 12 (14.8%) positive for S100. There was no gender
      difference in patients with CD117-positive GIST. Their mean age was 65 years.
      There were 44 (54%) tumors located in the stomach and 29 (36%) in the small
      intestine. The most frequent presenting symptoms were abdominal pain and GI
      bleeding. The mean tumor size was 7.5 +/- 5.7 cm. There were 35 cases (43.2%)
      with tumors >5 cm. The tumor size correlated significantly with tumor mitotic
      count and resectability. Tumor size, mitotic count, and resectability correlated
      significantly with tumor recurrence and survival. There was recurrent disease in
      39% of our patients, and their mean survival after recurrence was 16.6 months.
      Most recurrences were at the primary site or metastatic to the liver. Twenty-six
      percent of our patients died of their disease. CONCLUSION: Traditional histologic
      criteria are not specific enough to diagnose GIST. This diagnosis must be
      confirmed with CD117 immunohistochemical staining. Prognosis is dependent on
      tumor size, mitotic count, and resectability.

PMID- 14669340
TI  - Eosinophilic gastroenteritis: clinical experience with 15 patients.
AB  - AIM: To evaluate the clinic features of eosinophilic gastroenteritis and to
      examine the diagnosis, treatment, long-term outcome of this disease. METHODS:
      Charts with a diagnosis of eosinophilic gastroenteritis from 1984 to 2002 at
      Mackay Memorial Hospital were reviewed retrospectively. There were 15 patients
      diagnosed with eosinophilic gastroenteritis. The diagnosis was established in 13
      by histologic evaluation of endoscopic biopsy or operative specimen and in 2 by
      radiologic imaging and the presence of eosinophilic ascites. RESULTS: All the
      patients had gastrointestinal symptoms and 12 (80%) had hypereosinophilia
      (absolute eosinophil count 1,008 to 31,360/cm3). The most common symptoms were
      abdominal pain and diarrhea. Five of the 15 patients had a history of allergy.
      Seven patients had involvement of the mucosa, 2 of muscularis, and 6 of
      subserosa. One with a history of seafood allergy was successfully treated with an
      elimination diet. Another patient improved spontaneously after fasted for several
      days. The remaining 13 patients were treated with oral prednisolone, 10 to 40
      mg/day initially, which was then tapered. The symptoms in all the patients
      subsided within two weeks. Eleven of the 15 patients were followed up for more
      than 12 months (12 to 104 months, mean 48.7), of whom 5 had relapses after
      discontinuing steroids (13 episodes). Two of these patients required long-term
      maintenance oral prednisolone (5 to 10 mg/day). CONCLUSION: Eosinophilic
      gastroenteritis is a rare condition of unclear etiology characterized by relapses
      and remissions. Short courses of corticosteroids are the mainstay of treatment,
      although some patients with relapsing disease require long-term low-dose
      steroids.

PMID- 14669341
TI  - Correlation of P-glycoprotein expression with poor vascularization in human
      gallbladder carcinomas.
AB  - AIM: To investigate the relationship between the expression of P-glycoprotein (P
      gp) and the degree of vascularization in gallbladder carcinomas. METHODS: P-gp
      was stained with streptavidin-peroxidase complex immunohistochemical method in
      routine paraffin-embedded sections of gallbladder carcinomas. Microvessel counts
      (MVC) were determined using factor-VIII-related antigens. RESULTS: The average
      MVC in 32 cases of gallbladder carcinomas was (34 +/- 10)/HP. The value of MVC
      was closely correlated with Nevin staging and tumor differentiation (P<0.01 and
      P<0.05). The total expression rate of P-gp was 62.5%. The P-gp expression rate in
      cases of Nevin staging S1-S3 (78.6%) was higher than that of S4-S5 (50.0%) with
      no statistical significance. The P-gp expression rate was not correlated with
      tumor differentiation or pathologic types. The value of MVC in P-gp (+) cases was
      markedly lower than that in P-gp (-) cases (P<0.01). The positive rate of P-gp
      was significantly higher in cases of smaller MVC than those of bigger MVC
      (P<0.05). CONCLUSION: MVC may be used as one of the important parameters to
      reflect the biological behaviors of gallbladder carcinomas. As a major cause of
      drug resistance, the overexpression of P-gp is closely correlated with the poor
      vascularization in gallbladder carcinomas.

PMID- 14669342
TI  - Clinical predictors of severe gallbladder complications in acute acalculous
      cholecystitis.
AB  - AIM: To evaluate the relationship between clinical information (including age,
      laboratory data, and sonographic findings) and severe complications, such as
      gangrene, perforation, or abscess, in patients with acute acalculous
      cholecystitis (AAC). METHODS: The medical records of patients hospitalized from
      January 1997 to December 2002 with a diagnosis of acute cholecystitis were
      retrospectively reviewed to find those with AAC, confirmed at operation or by
      histologic examination. Data collected included age, sex, white blood cell count,
      AST, total bilirubin, alkaline phosphatase, bacteriology, mortality, and
      sonographic findings. The sonographic findings were recorded on a 3-point scale
      with 1 point each for gallbladder distention, gallbladder wall thickness >3.5 mm,
      and sludge. The patients were divided into 2 groups based on the presence (group
      A) or absence (group B) of severe gallbladder complications, defined as
      perforation, gangrene, or abscess. RESULTS: There were 52 cases of AAC,
      accounting for 3.7% of all cases of acute cholecystitis. Males predominated. Most
      patients were diagnosed by ultrasonography (48 of 52) or computed tomography (17
      of 52). Severe gallbladder complications were present in 27 patients (52%, group
      A) and absent in 25 (group B). Six patients died with a mortality of 12%. Four of
      the 6 who died were in group A. Patients in group A were significantly older than
      those in group B (mean 60.88 y vs. 54.12 y, P=0.04) and had a significantly
      higher white blood cell count (mean 15,885.19 vs. 9,948.40, P=0.0005). All the 6
      patients who died had normal white blood cell counts with an elevated percentage
      of band forms. The most commonly cultured bacteria in both blood and bile were E.
      coli and Klebsiella pneumoniae. The cumulative sonographic points did not
      reliably distinguish between groups A and B, even though group A tended to have
      more points. CONCLUSION: Older patients with a high white cell count are more
      likely to have severe gallbladder complications. In these patients, earlier
      surgical intervention should be considered if the sonographic findings support
      the diagnosis of AAC.

PMID- 14669344
TI  - Overexpression of Caspase-1 in adenocarcinoma of pancreas and chronic
      pancreatitis.
AB  - AIM: To identify the expression of Caspase-1(interleukin-1beta converting enzyme)
      and its role in adenoma of the pancreas and chronic pancreatitis. METHODS: The
      expression of Caspase-1 was assessed in 42 pancreatic cancer tissue samples, 38
      chronic pancreatitis specimens, and 9 normal pancreatic tissues by
      immunohistochemistry and Western blot analysis. RESULTS: Overexpression of
      Caspase-1 was observed in both disorders, but there were differences in the
      expression patterns in distinct morphologic compartments. Pancreatic cancer
      tissues showed a clear cytoplasmatic overexpression of Caspase-1 in tumor cells
      of 71% of the tumors, whereas normal pancreatic tissues showed only occasional
      immunoreactivity. In chronic pancreatitis, overexpression of Caspase-1 was found
      in atrophic acinar cells (89%), hyperplastic ducts (87%), and dedifferentiating
      acinar cells (84%). Although in atrophic cells a clear nuclear expression was
      found, hyperplastic ducts and dedifferentiating acinar cells showed clear
      cytoplasmic expression. Western blot analysis revealed a marked expression of the
      45 kDa precursor of Caspase-1 in pancreatic cancer and chronic pancreatitis (80%
      and 86%, respectively). Clear bands at 30 kDa, which suggested the p10-p20
      heterodimer of active Caspase-1, were found in 60% of the cancer tissue and 14%
      of the pancreatitis tissue specimens, but not in normal pancreatic tissues.
      CONCLUSION: Overexpression of Caspase-1 is a frequent event in pancreatic
      disorders and its differential expression patterns may reflect two functions of
      the protease. One is its participation in the apoptotic pathway in atrophic
      acinar cells and tumor-surrounding pancreatitis tissue, the other is its possible
      role in proliferative processes in pancreatic cancer cells and hyperplastic duct
      cells and dedifferentiating acinar cells in chronic pancreatitis.

PMID- 14669343
TI  - Imaging diagnosis of pancreato-biliary diseases: a control study.
AB  - AIM: To evaluate the clinical value of various imageological methods in
      diagnosing the pancreato-biliary diseases and to seek the optimal procedure.
      METHODS: Eighty-two cases of pancreato-biliary diseases confirmed by surgery and
      pathology were analyzed. There were 38 cases of cholelithiasis, 34 cases of
      pancreato-biliary tumors and 10 other cases. The imageological methods included B
      US, CT, ERCP, PTC, cross-sectional MRI and MR cholangiopancreatography (MRCP).
      RESULTS: The accuracy rate of MRCP in detecting the location of pancreato-biliary
      obstruction was 100%. In differentiating malignant from benign obstruction, the
      sensitivity of the combination of MRCP and cross-sectional MRI was 82.3%, the
      specificity was 93.8%, and the accuracy rate was 89.0%. The accuracy rate for
      determining the nature of obstruction was 87.8%, which was superior to that of B
      US (P=0.0000) and CT (P=0.0330), but there was no significant difference between
      direct cholangiopancreatography and the combination of MRCP and conventional MRI
      (P=0.6666). CONCLUSION: In most cases, MRCP can substitute direct
      cholangiopancreatography for diagnosis. The combination of MRCP and cross
      sectional MRI should be considered as an important means in diagnosing the
      pancreato-biliary diseases, pre-operative assessment and post-operative follow
      ups.

PMID- 14669345
TI  - Spider angiomas in patients with liver cirrhosis: role of vascular endothelial
      growth factor and basic fibroblast growth factor.
AB  - AIM: To investigate whether vascular endothelial growth factor (VEGF) and basic
      fibroblastic growth factor (bFGF) are associated with spider angiomas in patients
      with liver cirrhosis. METHODS: Eighty-six patients with liver cirrhosis were
      enrolled and the number and size of the spider angiomas were recorded. Fifty
      three healthy subjects were selected as controls. Plasma levels of VEGF and bFGF
      were measured in both the cirrhotics and the controls. RESULTS: Plasma VEGF and
      bFGF were increased in cirrhotics compared with controls (122 +/- 13 vs. 71 +/-
      11 pg/mL, P=0.003 for VEGF; 5.1 +/- 0.5 vs. 3.4 +/- 0.5 pg/mL, P=0.022 for bFGF).
      In cirrhotics, plasma VEGF and bFGF were also higher in patients with spider
      angiomas compared with patients without spider angiomas (185 +/- 28 vs. 90 +/- 10
      pg/mL, P=0.003 for VEGF; 6.8 +/- 1.0 vs. 4.1 +/- 0.5 pg/mL, P=0.017 for bFGF).
      Multivariate logistic regression showed that young age and increased plasma
      levels of VEGF and bFGF were the most significant predictors for the presence of
      spider angiomas in cirrhotic patients (odds ratio [OR]=6.64, 95 % confidence
      interval [CI]=2.02-21.79, P=0.002; OR=4.35, 95% CI=1.35-14.01, P=0.014; OR=5.66,
      95% CI=1.72-18.63, P=0.004, respectively). CONCLUSION: Plasma VEGF and bFGF are
      elevated in patients with liver cirrhosis. Age as well as plasma levels of VEGF
      and bFGF are significant predictors for spider angiomas in cirrhotic patients.

PMID- 14669346
TI  - Copper metabolism after living related liver transplantation for Wilson's
      disease.
AB  - AIM: Liver transplantation is indicated for Wilson's disease (WD) patients with
      the fulminant form and end-stage liver failure. The aim of this study was to
      review our experience with living-related liver transplantation (LRLT) for WD.
      METHODS: A retrospective review was made for WD undergoing LRLT at our hospital
      from January 2001 to February 2003. RESULTS: LRLT was carried out in 15 patients
      with WD, one of them had fulminant hepatic failure and the others had end-stage
      hepatic insufficiency. The mean age of the patients was 14.5 +/- 2.5 years (range
      6 to 20 years). All the recipients had low serum ceruloplasmin levels with a mean
      value of 126.8 +/- 34.8 mg/L before transplantation. The serum ceruloplasmin
      levels increased to an average of 238.6 +/- 34.4 mg/L after LRLT at the latest
      evaluation, between 2 and 27 months after transplantation. A marked reduction in
      urinary copper excretion was observed in all the recipients after
      transplantation. Among the eight recipients with preoperative Kayser-Fleischer (K
      F) rings, this abnormality resolved completely after LRLT in five patients and
      partially in three. All the recipients are alive and remain well, and none has
      developed signs of recurrent WD after a mean follow-up period of 15.4 +/- 9.3
      months (range 2-27 months) except one who died of severe rejection. The donors
      were 14 mothers and 1 father. The serum ceruloplasmin levels were within normal
      limits in all the donors (mean: 220 +/- 22.4 mg/L). The mean donor age was 35.0
      +/- 4.0 years (range, 30 to 45 years). Two donors had biliary leakage and
      required reoperation. Grafts were harvested as follows: four right lobe grafts
      without hepatic middle vein and eleven left lobe grafts with hepatic middle vein.
      The grafts were blood group-compatible in all recipients. Two patients had
      hepatic artery thrombosis and underwent retransplantation. CONCLUSION: LRLT is a
      curative procedure in Wilson's disease manifested as fulminant hepatic failure
      and/or end-stage hepatic insufficiency. After liver transplantation, the serum
      ceruloplasmin level can increase to its normal range while urinary copper
      excretion decreases. Grafts chosen from heterozygote carriers do not appear to
      confer any risk of recurrence in recipients.

PMID- 14669348
TI  - Plasma matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 as
      biomarkers of ulcerative colitis activity.
AB  - AIM: Overexpression of mucosal metalloproteinases (MMP) has been demonstrated
      recently in inflammatory bowel disease. Their activity can be counterbalanced by
      the tissue inhibitor of metalloproteinases (TIMP). The aim of this study was to
      evaluate the effect of ulcerative colitis (UC) on MMP-1 and TIMP-1 plasma
      concentrations, as two possible biomarkers of the disease activity. METHODS: MMP
      1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 16
      patients with endoscopically confirmed active UC. RESULTS: Plasma concentrations
      of both MMP-1 (13.7 +/- 0.2 ng/ml) and TIMP-1 (799 +/- 140 ng/ml) were
      significantly elevated in UC patients in comparison to healthy controls (11.9 +/-
      0.9 ng/ml and 220 +/- 7 ng/ml respectively). There was no correlation between
      TIMP-1 and MMP-1 concentrations (r=-0.02). TIMP-1 levels revealed significant
      positive correlations with scored endoscopic degree of mucosal injury, disease
      activity index and clinical activity index values as well as C-reactive protein
      concentration. There was no correlation between MMP-1 and laboratory, clinical or
      endoscopic indices of the disease activity. CONCLUSION: These results confirm the
      role of both MMP-1 and TIMP-1 in the pathogenesis of ulcerative colitis. However
      only TIMP-1 can be useful as a biomarker of the disease activity, demonstrating
      association with clinical and endoscopic pictures.

PMID- 14669347
TI  - Clinical relationship between EDN-3 gene, EDNRB gene and Hirschsprung's disease.
AB  - AIM: To investigate the mutation of EDNRB gene and EDN-3 gene in sporadic
      Hirschsprung's disease (HD) in Chinese population. METHODS: Genomic DNA was
      extracted from bowel tissues of 34 unrelated HD patients which were removed by
      surgery. Exon 3, 4, 6 of EDNRB gene and Exon 1, 2 of EDN-3 gene were amplified by
      polymerase chain reaction (PCR) and analyzed by single strand conformation
      polymorphism (SSCP). RESULTS: EDNRB mutations were detected in 2 of the 13 short
      segment HD. One mutant was in the exon 3, the other was in the exon 6. EDN-3
      mutation was detected in one of the 13 short-segment HD and in the exon 2. Both
      EDNRB and EDN-3 mutations were detected in one short-segment HD. No mutations
      were detected in the ordinary or long-segment HD. CONCLUSION: The mutations of
      EDNRB gene and EDN-3 gene are found in the short-segment HD of sporadic
      Hirschsprung's disease in Chinese population, which suggests that the EDNRB gene
      and EDN-3 gene play important roles in the pathogenesis of HD.

PMID- 14669349
TI  - Gastric pseudolipomatosis, usual or unusual? Re-evaluation of 909 endoscopic
      gastric biopsies.
AB  - Microvesicular pneumatosis intestinalis, also called "pseudolipomatosis" for
      resembling fatty infiltration, is characterized by the presence of small gas
      voids in the gastrointestinal wall, especially in mucosa. These voids are not
      lined with epithelia. There are few reported cases about colon, duodenum and
      skin. Because there is only one case report about pseudolipomatosis in the
      stomach, we re-evaluated 909 endoscopic biopsies taken from gastric corpus to
      check the presence of pseudolipomatosis. We determined pseudolipomatosis foci in
      3 percent (n=27) of biopsies. In two cases there were pseudolipomatosis foci in
      endoscopic biopsies having otherwise normal histologic findings, while there were
      pseudolipomatosis foci in endoscopic biopsies of 25 patients with gastritis. H
      pylori was found in 85% of biopsies having pseudolipomatosis foci. In this study,
      we presented some histopathologic characteristics of pseudolipomatosis seen in
      gastric mucosa.

PMID- 14669350
TI  - Oddi sphincter function after canine auto-pancreas transplantation with bladder
      drainage.
AB  - AIM: Several neural and hormonal factors are known to affect motility of
      sphincter of Oddi (SO). The major roles of SO are to regulate the flow of bile
      and pancreatic juice into the duodenum and to prevent the reflux of duodenal
      contents into the biliary and pancreatic duct. After pancreas transplantation,
      graft SO was denervated and graft pancreatitis might have relations to SO
      motility. The motility of SO after canine pancreas transplantation with bladder
      drainage was investigated. METHODS: Normal canine SO manometry and pancreas graft
      SO manometry after pancreas transplantation with bladder drainage were performed
      in seven dogs respectively before and after cholecystokinin (CCK) administration.
      Data of SO basal pressure, contraction frequency, amplitude and motility index
      after transplantation and CCK administration were compared with that in controls
      and before CCK administration. RESULTS: SO showed regular contractions with a
      certain basal pressure in control dogs. After transplantation, the graft SO basal
      pressure and contraction frequency were higher than that in controls, but the
      amplitude decreased (P<0.01). There was no great difference in SO motility index.
      CCK administration could relax normal SO but stimulate graft SO after pancreas
      transplantation with bladder drainage. After CCK administration, SO basal
      pressure, frequency and motility index were increased significantly (P<0.05), in
      comparison with that before administration. The amplitude remained unchanged
      (P>0.05), in comparison with that before CCK administration. CONCLUSION: After
      auto-pancreas transplantation with bladder drainage, canine SO motility was
      inhibited. Basal pressure and frequency increased but amplitude decreased. CCK
      administration after transplantation had an inhibitory effect on canine SO
      instead of a relaxation effect observed in normal canine SO. This will increase
      the resistance of SO to the pancreatic juice flow and induce pancreatic juice
      stagnation and can not prevent reflux of urine and duodenal contents when the
      bladder pressure is increased to a certain extent, which may cause graft
      pancreatitis.

PMID- 14669351
TI  - Incidence and treatment of hepatic artery complications after orthotopic liver
      transplantation.
AB  - AIM: To investigate the incidence and treatment of hepatic artery complications
      after orthotopic liver transplantation. METHODS: From February 1999 to May 2002,
      orthotopic liver transplantations (OLT) were performed in 72 patients with end
      stage liver diseases with an average age of 40.2 +/- 13.6 years (ranged from 11
      to 68 years), 56 were males and 16 females. The preoperative evaluation for the
      72 patients was performed using duplex sonography, abdominal CT scan, and
      angiography of the hepatic artery. All donor grafts were perfused and preserved
      in University of Wisconsin solution at 4 degrees. OLT was performed with standard
      techniques with or without a veno-venous bypass. Reconstructions of hepatic
      artery were performed between the branch patches of gastroduodenal/hepatic or
      splenic/common hepatic artery confluence of the donors and recipients, and an end
      to-end anastomosis between other arterial vessels of the donors and recipients
      was done. Arterial anastomosis was performed with interrupted 7-0/8-0
      monofilament polypropylene suture under 3.5 x loupe magnification. Diagnosis of
      the complications of hepatic artery after OLT was based on the clinical
      presentations, ultrasound findings and arterial angiography. All patients were
      followed up regularly for duplex ultrasound scan after discharge. RESULTS: The
      overall incidence of arterial complications in 72 patients after OLTs was 1.4%
      (1/72). One 3 cm pseudoaneurysm at the side of anastomotic site of hepatic artery
      was found by urgent arteriogram due to hemoperitoneum secondary to bile leakage
      after OLT. Subsequently the pseudoaneurysm was successfully embolized and the
      blood flow toward the donor liver in hepatic artery remained. The overall
      postoperative 30-day mortality rate was 8.33%. The one-year survival rate was
      83.72% in 50 patients with benign diseases and was 71.43% in 22 patients with
      malignant diseases following OLT. No death associated with complications of
      hepatic artery occurred. CONCLUSION: Careful preoperative evaluations and
      intraoperative microsurgical technique for hepatic artery reconstructions are the
      keys in prevention of hepatic artery complications after OLT.

PMID- 14669352
TI  - Management of choledocholithiasis: comparison between laparoscopic common bile
      duct exploration and intraoperative endoscopic sphincterotomy.
AB  - AIM: Choledocholithiasis is present in 5 to 10 percent of patients who have
      cholelithiasis. In the area of laparoscopic cholecystectomy (LC), laparoscopic
      common bile duct exploration (LCBDE) and intraoperative endoscopic sphincterotomy
      (IOES) have been used to treat choledocholithiasis. The purpose of this study was
      to compare the clinical outcomes and hospital costs of LCBDE with IOES. METHODS:
      Between November 1999 and October 2002, patients with choledocholithiasis
      undergoing LC plus LCBDE (Group A, n=45) were retrospectively compared to those
      undergoing LC plus IOES (Group B, n=57) at a single institution. RESULTS: Ductal
      stone clearance rates were equivalent for the two groups (88% versus 89%,
      P=0.436). The conversion rate was higher for Group B (8.8% versus 4.4%, P=0.381),
      as was the morbidity (12.3% versus 6.7%, P=0.336). There were no other
      significant differences between the two groups. The complications were mainly
      related to endoscopic sphincterotomy (ES), and the hospital costs were
      significantly increased in this subset of Group B (median, 23,910 versus 14,955
      RMB yuan, P=0.03). Although hospital stay was longer in Group A (median, 7 versus
      6 days, P=0.041), the patients in Group A had a significantly decreased cost of
      hospitalization compared with those in Group B (median, 11,362 versus 15,466 RMB
      yuan, P=0.000). CONCLUSION: The results demonstrate equivalent ductal stone
      clearance rates for the two groups. LCBDE management appears safer, and is
      associated with a significantly decreased hospital cost. The findings suggest
      LCBDE for choledocholithiasis is a better option.

PMID- 14669353
TI  - Influence of liver nonparenchymal cell infusion combined with cyclosporin A on
      rejection of rat small bowel transplantation.
AB  - AIM: To investigate the effect of liver nonparenchymal cell infusion combined
      with cyclosporin A (CsA) on rejection of heterostrain rat small bowel
      transplantation. METHODS: The liver nonparenchymal cell suspension was prepared
      by density gradient centrifugation method with Percoll centrifugal solution.
      Heterotopic small bowel transplantation was performed. Then the rats were divided
      into four groups. Group one: homogenic transplantation (F344/N-F344/N), group
      two: allotransplantation (F344/N-Wistar), group three: allotransplantation
      (F344/N-Wistar) + CsA, with CsA 10 mg/kg(-1)/d(-1) after transplantation, group
      four: allotransplantation + CsA (F344/N-Wistar) + liver nonparenchymal cell
      infusion + CsA (F344/N-Wistar), in which recipient Wistar rats had been injected
      with 2x10(8) F344/N liver nonparenchymal cells 20 days before transplantation,
      and treated with CsA after transplantation. Finally, the survival time after
      small bowel transplantation, gross and histopathological examination, and IL-2
      levels in serum were observed. RESULTS: The survival time after small bowel
      transplantation was 7.14 +/- 0.33 d, 16.32 +/- 0.41 d and 31.41 +/- 0.74 d in
      group 2, 3, and 4, respectively. The survival time was significant longer
      (P<0.01) in group 4. The gross and histopathological examination showed that the
      rejection degree in group 4 was lower than those in groups 2 and 3. Serum IL-2
      level in group 4 was also lower than those in groups 2 and 3 (P<0.01).
      CONCLUSION: Liver nonparenchymal cell infusion combined with CsA can prolong the
      survival time of rat small bowel transplantation, and the anti-rejection effect
      is good.

PMID- 14669354
TI  - Expression of PCNA and CD44mRNA in colorectal cancer with venous invasion and its
      relationship to liver metastasis.
AB  - AIM: To investigate the expression of proliferating cell nuclear antigen (PCNA)
      and CD44mRNA in colorectal cancer with venous invasion and its relationship with
      liver metastasis. METHODS: Reverse transcriptase-polymerase chain reaction (RT
      PCR) was used to detect the expression of PCNA and CD44mRNA in 31 cases of
      colorectal cancer with venous invasion. RESULTS: Positive expression rates of
      PCNA and CD44mRNA in colorectal cancer were higher than those without liver
      metastasis (P<0.05 and P<0.01). In case of colorectal cancer with liver
      metastasis, strongly positive rates of PCNA and CD44mRNA were 94.1% and 70.6%,
      respectively, significantly higher than those without liver metastasis. There was
      a positive relationship between the expressions of PCNA and CD44mRNA (r=0.67,
      P<0.05). CONCLUSION: Detection of PCNA and CD44mRNA expression in colorectal
      cancer may be useful for evaluating liver metastasis of cancer cells.

PMID- 14669355
TI  - Relationship between expression of CD105 and growth factors in malignant tumors
      of gastrointestinal tract and its significance.
AB  - AIM: Angiogenesis is an important step in the growth of solid malignant tumors. A
      number of angiogenic factors have been found such as transforming growth factor
      beta1 (TGF-beta1) and vascular endothelial growth factor (VEGF). However, the
      roles of TGF-beta1 and VEGF in gastrointestinal carcinogenesis are still unclear.
      This study was to investigate the expressions of TGF-beta1 and VEGF in
      gastrointestinal tract malignant tumors, as well as their association with
      microvessel density (MVD). At the same time, we also observed the localization of
      TGF-beta1 and its receptor CD105 in gastric malignant tumors. METHODS: The
      expressions of TGF-beta1 and CD105 were detected in 55 fresh specimens of gastric
      carcinoma and VEGF and CD105 in 44 fresh specimens of colorectal carcinoma by
      immunohistochemical staining (S-ABC). TGF-beta1 and CD105 in 55 gastric carcinoma
      tissues on the same slide were detected by using double-stain
      Immunohistochemistry (DS-ABC). RESULTS: Among the 55 cases of gastric carcinoma
      tissues, 30 were positive for TGF-beta1 (54.55%). The MVD of TGF-beta1 strong
      positive group (++ approximately +++ 23.22 +/- 5.8) was significantly higher than
      that of weak positive group (+17.56 +/- 7.2) and negative group (- 17.46 +/- 3.9)
      (q=4.5, q=5.3207, respectively, P<0.01). In the areas of high expression of TGF
      beta1, MVD and the expression of CD105 were also high. Among the 44 cases of
      colonic carcinoma tissues, 26 were positive for VEGF (59.1%). The expressions of
      both VEGF and CD105 (MVD) were related with the depth of invasion (F=5.438,
      P<0.05; F=4.168, P=0.05), lymph node metastasis (F=10.311, P<0.01; F=20.282,
      P<0.01) and Dukes stage (F=6.196, P<0.01; F=10.274, P<0.01), but not with
      histological grade (F=0.487, P>0.05). There was a significant correlation between
      the expression of VEGF and CD105 (MVD) (r=0.720, P<0.01). CONCLUSION: Over
      expression of TGF-beta1 and VEGF acts as stimulating factors of angiogenesis in
      gastrointestinal tumors. CD105, as a receptor of TGF-beta1, can regulate the
      biological effect of TGF-beta1 in tumor angiogenesis. MVD marked by CD105 is more
      suitable for detecting newborn blood vessels.

PMID- 14669357
TI  - Bouveret's syndrome complicated by a distal gallstone ileus.
AB  - AIM: Gastric outlet obstruction caused by duodenal impaction of a large gallstone
      migrated through a cholecystoduodenal fistula has been referred as Bouveret's
      syndrome. Endoscopic lithotomy is the first-step treatment, however, surgery is
      indicated in case of failure or complication during this procedure. METHODS: We
      report herein an 84-year-old woman presenting with features of gastric outlet
      obstruction due to impacted gallstone. She underwent an endoscopic retrieval
      which was unsuccessful and was further complicated by distal gallstone ileus.
      Physical examination was irrelevant. RESULTS: Endoscopy revealed multiple
      erosions around the cardia, a large stone in the second part of the duodenum
      causing complete obstruction, and wide ulceration in the duodenal wall where the
      stone was impacted. Several attempts of endoscopic extraction by using foreign
      body forceps failed and surgical intervention was mandatory. Preoperative
      ultrasound evidenced pneumobilia whilst computerized tomography showed a large
      stone, 5 cm x 4 cm x 3 cm, logging at the proximal jejunum and another one, 2.5
      cm x 2 cm x 2 cm, in the duodenal bulb causing a closed-loop syndrome. She
      underwent laparotomy and the jejunal stone was removed by enterotomy. Another
      stone reported as located in the duodenum preoperatively was found to be present
      in the gallbladder by intraoperative ultrasound. Therefore, cholecystoduodenal
      fistula was broken down, the stone was retrieved and cholecystectomy with
      duodenal repair was carried out. She was discharged after an uneventful
      postoperative course. CONCLUSION: As the simplest and the least morbid procedure,
      endoscopic stone retrieval should be attempted in the treatment of patients with
      Bouveret's syndrome. When it fails, surgical lithotomy consisting of simple
      enterotomy may solve the problem. Although cholecystectomy and cholecystoduodenal
      fistula breakdown is unnecessary in every case, conditions may urge the surgeon
      to perform such operations even though they carry high morbidity and mortality.

PMID- 14669356
TI  - Pedunculated rectal carcinoid removed by endoscopic mucosal resection: a case
      report.
AB  - Carcinoid tumors generally appear as yellow/gray or tan submucosal nodules. We
      experienced a case of pedunculated rectal carcinoid showing a mushroom-like
      appearance. The case was a forty years old woman who was admitted to our hospital
      due to rectal bleeding. Colonoscopy revealed a pedunculated polyp presenting a
      mushroom-shaped appearance measuring 13 mm in diameter in the rectum. The
      histological diagnosis of specimens obtained by biopsy was adenocarcinoma and
      transanal ultrasonography revealed the tumor localization within the submucosal
      layer in the rectum. Endoscopic mucosal resection (EMR) was performed.
      Histopathological examination established the diagnosis of carcinoid tumor in the
      rectum. Frequencies of the pedunculated type in rectal carcinoids were reported
      to be 2.4% to 7.1% in the literature. Because of its rarity, pedunculated
      configuration may confuse the endoscopic diagnosis of carcinoids. Treatment for
      carcinoids of 1 to 1.5 cm in size remains controversial. Although such tumors are
      technically respectable by EMR, careful attention must be paid in dealing with
      these tumors because there may be unexpected behaviors of the tumors.

PMID- 14669358
TI  - Icteric flare of chronic hepatitis B in a 95-year old patient.
AB  - A 95-year old gentleman developed fatal icteric flare of chronic hepatitis B
      despite lamivudine treatment. This article highlights the atypical presentations
      of chronic hepatitis B in elderly patient and the need to consider this
      possibility for acute fulminant hepatitis in endemic areas.

PMID- 14669359
TI  - Pseudoaneurysm of gastroduodenal artery following radical gastrectomy for gastric
      carcinoma patients.
AB  - We report a rare case of postoperative pseudoaneurysm of the gastroduodenal
      artery following radical gastrectomy. Surgical trauma to the gastroduodenal
      artery during regional lymphadenectomy was considered as the cause of the
      postoperative pseudoaneurysm. The pseudoaneurysm was successfully managed by
      ligating the bleeding vessel. We should consider the possibility of
      pseudoaneurysm formation in a patient with gastrointestinal bleeding in the
      postoperative period following radical gastrectomy with regional lymph node and
      perivascular lymphatic dissection.

PMID- 14669360
TI  - Surgical resection of duodenal lymphangiectasia: a case report.
AB  - Intestinal lymphangiectasia, characterized by dilatation of intestinal lacteals,
      is rare. The major treatment for primary intestinal lymphangiectasia is dietary
      modification. Surgery to relieve symptoms and to clarify the etiology should be
      considered when medical treatment failed. This article reports a 49-year-old
      woman of solitary duodenal lymphangiectasia, who presented with epigastralgia and
      anemia. Her symptoms persisted with medical treatment. Surgery was finally
      performed to relieve the symptoms and to exclude the existence of underlying
      etiologies, with satisfactory effect. In conclusion, duodenal lymphangiectasia
      can present clinically as epigastralgia and chronic blood loss. Surgical
      resection may be resorted to relieve pain, control bleeding, and exclude
      underlying diseases in some patients.

PMID- 14669361
TI  - Life-threatening hemobilia caused by hepatic artery pseudoaneurysm: a rare
      complication of chronic cholangitis.
AB  - Hemobilia is one of the causes of obscure gastrointestinal haemorrhage. Most
      cases of hemobilia are of iatrogenic or traumatic origin. Hemobilia caused by a
      hepatic artery pseudoaneurysm due to ascending cholangitis is very rare and its
      mechanism is unclear. We report a 74-year-old woman with a history of surgery for
      choledocholithiasis 30 years ago, suffering from a protracted course of life
      threatening gastrointestinal bleeding. A small intestines series and endoscopic
      retrograde cholangiopancreatography revealed a chronic cholangitis with marked
      contrast reflux into the biliary tree. Angiography confirmed the bleeding from a
      pseudoaneurysm of the middle hepatic artery. Coil embolization achieved
      successful hemostasis. We discussed the mechanism and reviewed the literature.

PMID- 14669362
TI  - Give us the money.

PMID- 14669363
TI  - Hue and outcry.

PMID- 14669364
TI  - News exclusive.

PMID- 14669365
TI  - Question time.

PMID- 14669366
TI  - We genuinely do not know what it is we want and need to say. The only way to know
      is to try.

PMID- 14669368
TI  - Life ensuring.

PMID- 14669367
TI  - Appealing against a bad benefits decision can be a pretty unappealing prospect.

PMID- 14669369
TI  - Cinderellas of the psyche.

PMID- 14669370
TI  - Emotional knowing.

PMID- 14669371
TI  - Keeping in touch.

PMID- 14669372
TI  - Letting through light.

PMID- 14669373
TI  - Beyond us and them.

PMID- 14669374
TI  - Diatribe.

PMID- 14669376
TI  - Upstream downstream.

PMID- 14669375
TI  - This life.

PMID- 14669377
TI  - The sounds of music.

PMID- 14669378
TI  - Best in show.

PMID- 14669379
TI  - Stepping stones.

PMID- 14669380
TI  - From the top.

PMID- 14669381
TI  - Five portions a day.

PMID- 14669382
TI  - The emperor's new clothes.

PMID- 14669383
TI  - Leading lights to guide us.

PMID- 14669384
TI  - Prayers, parties and participation.

PMID- 14669385
TI  - Improving response to terror and global emerging infectious disease.

PMID- 14669386
TI  - Creating a health care agenda for the Department of Homeland Security.
AB  - The challenge before us at DHS--to optimize use of our resources to create an
      effective health response to terrorist incidents--is formidable. After spending
      several weeks in Baghdad and seeing all the problems that arise in establishing a
      new government, I found myself thinking, "This is going to take years." Then,
      when I returned to the United States, Surgeon General Vice Adam. Richard Carmona,
      MD, MPH, almost immediately assigned me to the new Department of Homeland
      Security, adding that the problems it faced were probably worse than those in
      Baghdad. "That is impossible," I thought. "There's no way this could present a
      greater logistical, organizational, cultural, and administrative challenge than
      establishing a new government in a country with no democratic tradition in its
      5,000-year history!" Within two days of my appointment to the new department,
      however, I recognized the accuracy of the surgeon general's statement. We will,
      however, work diligently toward our goals. During the next couple of years, a
      major DHS priority will be state and local preparedness, which includes rapid
      identification of epidemics, improved training, the establishment of liaisons
      with other first responders such as fire, rescue, law enforcement, and emergency
      medical services teams, and implementing state-of-the-art communication, disease
      alert, and reporting systems. Table 2 constitutes a checklist for bioterrorism
      preparedness, from a public health perspective. Local response and coordination
      with federal authorities and the issues inherent in these efforts are discussed
      in depth in the presentations that begin on the following page of this
      publication.

PMID- 14669387
TI  - Bioterror emergency readiness: a local responsibility.

PMID- 14669388
TI  - Setting research priorities for disaster preparedness: the role of AHRQ.

PMID- 14669389
TI  - Health care's counterterrorism efforts: what's being done and what isn't.

PMID- 14669390
TI  - [Comparison of cerclage and cerclage pessary in the treatment of pregnant women
      with incompetent cervix and threatened preterm delivery].
AB  - Cervical incompetence is one of the causes of preterm delivery. Ultrasound
      examination of the cervix has given the evidence that cervical shortening,
      dilatation of internal cervical os and funneling observed long before term are
      the warning signs of preterm delivery. Early diagnosis and treatment may serve
      better outcome. Cerclage, which has been employed for more than 50 years is a
      traumatic procedure, furthermore requiring anaesthesia. Cerclage pessary can be a
      safe alternative to cerclage. This method seems to be less invasive. The aim of
      the study was to compare the effectiveness of the two methods employed in gravid
      patients between 22 and 27 completed weeks of pregnancy with clinically and
      ultrasonographically confirmed shortening of the cervix. MATERIAL AND METHODS: We
      analysed 57 patients, 22 treated with McDonald cerclage procedure and 35 with
      pessary. The primary outcome measure was prolongation of pregnancy--mean 13.4
      weeks and 12.1 weeks for cerclage and pessary respectively (p = 0.06). There were
      no significant differences regarding the mode of delivery, rate of prematurity,
      mean birthweight and Apgar score. CONCLUSIONS: Cerclage and cerclage pessary are
      equally effective methods of prolongation of pregnancy in gravid patients with
      incompetent cervix and threatened preterm labor. The choice of the method does
      not affect the mode of delivery as well as neonatal outcome.

PMID- 14669391
TI  - [Usefulness of determination of granulocyte elastase plasma level, c-reactive
      protein and white blood cell count in prediction in intrauterine infection in
      pregnant women after PROM].
AB  - The main markers of intrauterine infection: C-reactive protein and white blood
      cell count are dependent on medical management as steroids or antibiotics
      therapy. Granulocyte elastase is independent variable from influence of
      tocolysis, steroids, antibiotics, chemiotherapeutics, hours since PROM. The aim
      of the study was to evaluate and compare the usefulness of determination
      granulocyte elastase, (EG) C-reactive protein (CRP) and white blood cell count
      (WBC) in prediction of chorioamninitis in pregnant women after premature rupture
      of fetal membranes. MATERIALS AND METHODS: 67 women with single pregnancy between
      24-36 week of gestation after PPROM were included into the study group. All women
      were managed expectantly (tocolysis, antibiotics, steroids, intravaginal
      chemiotherapeutics, bed rest), maternal and fetal (KTG, USG) vital signs were
      monitored every day. EG, CRP and WBC blood test were performed every day.
      Histopathologic examinations of all placentas were performed for chorioamnionitis
      confirmation or exclusion. Normal range for EG--88 micrograms/l, CRP--15
      micrograms/l, WBC--15 x 10(9). RESULTS: The usefulness of granulocyte elastase
      plasma serial determination as biochemical marker of chorioamnionitis in cases of
      PPROM was confirmed: sensitivity--100%, specificity--33%, PPV--64.9%, NPV--100%
      in comparison with CRP: sensitivity--27%, specificity--80%, PPV--62.5%, NPV--47%
      and white blood cell count: sensitivity--27%, specificity--66.7%, PPV--50%, NPV
      42.5%. CONCLUSIONS: We confirmed statistical correlation (p < 0.001) between
      granulocyte elastase plasma level > 88 micrograms/l and histological signs of
      intrauterine infection in pregnant women after PPROM. Granulocyte elastase
      determination in plasma is most sensitive indicator of histologic confirmed
      chorioamnionitis.

PMID- 14669392
TI  - [Thyroid function in pregnant women with pregnancy induced hypertension].
AB  - OBJECTIVE: The aim of this study is to investigate thyroid's function in pregnant
      women with pregnancy induced hypertension. MATERIALS AND METHODS: 42 pregnant
      women with PIH diagnosed after 20 weeks of gestation (between 22-30 hbd) were
      hospitalized in Department of Obstetrics and Gynecology of Mother and Child
      Institute in Warsaw. This group consisted 20 multiparous and 22 primiparous. We
      measured thyroid hormone levels: TSH, fT4, fT3 and TBG. RESULTS: In 8 pregnant
      women (5 primiparous and 3 multiparous) thyroid function was normal (normal level
      of TSH, fT3, fT4) and middle blood pressure in term of beginning of the study was
      155/100 mmHg. 34 pregnant women (19 primiparous and 15 multiparous) had abnormal
      thyroid function. 3 (1 primiparous and 2 multiparous) pregnant women of this
      group had subclinical hyperthyroidism (middle blood pressure in the beginning of
      the study was 155/105) and 31 (21 primiparous and 10 multiparous) had fT4 and fT3
      levels lower then normal range with normal TBG levels. In this group only one
      patient TSH level was higher then 5 mlU/l, which allows to recognize overt
      hypothyroidism. In other cases the results indicate the subclinical
      hypothyroidism. The middle blood pressure was 140/95 mmHg. CONCLUSION: 1. Thyroid
      dysfunction in pregnant women was concluded in 78.2% of tested group. 2.
      Subclinical hypothyroidism was concluded the most frequent in the tested group.
      3. The middle blood pressure at the term of beginning of the study was the lowest
      in pregnant women with hypothyroidism. 4. The thyroid function tests should be
      performed in all pregnant women with PIH.

PMID- 14669393
TI  - [Pregnancy and childbirth course after IVF-ET patients admitted to KMMP ICZMP on
      Lodz between 1996-2002].
AB  - THE AIM: The evaluation of pregnancy course and the birth body weight of the
      infants from the women, which got pregnant as a result of IVF-ET procedures.
      MATERIALS AND METHODS: 72 female patients admitted to KMMP ICZMP in Lodz between
      January 1996 and December 2002 were put to the analysis (group I). The control
      group consisted of 400 random chosen female patients admitted to the Clinic
      during the examined period (group II). The course of the pregnancy, childbirth
      and the birth body weight of infants in both groups since 23rd week of the
      pregnancy were analysed. Mean age of the female patients in group I amounted 32
      years (22-42), and in the group II 26 years (17-37). For the purposes of
      statistic analyse the test chi 2 was used. RESULTS: In group I the patients
      presented significantly elder population then in the group II. The multiple
      pregnancies in the group I presented 32% and they occurred significantly more
      often then in the group II (2%). In the group I significantly statistically more
      often the cholestase (6.9%), the imminent premature childbirth (36%), the
      premature amniorrhoea (20.8%), the premature childbirth (22%), the isthmo-
      cervicalis insufficiency (6.9%) and the inhibition of the intrauterine foetus
      growth (11%) were affirmed. Statistically significantly more often the childbirth
      was ended with Caesarean section in the group I (47.2%) then in group II (17.8%).
      The infants with birth body weight less than 2500 g statistically significantly
      more often were born from group I (36.4%) then from group II (8.6%). CONCLUSION:
      1. The pregnancy and childbirth course after IVF-ET is burden with bigger risk of
      obstetric pathology occurrence. 2. The pregnant women after IVF-ET are more often
      giving birth to the infants with low birth body weight.

PMID- 14669394
TI  - [Effectiveness of recombinant activated factor VIIA (NovoSeven) in case of severe
      obstetric complication with coagulopathy].
AB  - The aim of report is to present the possibilities of applying NovoSeven in
      serious coagulopathy in course of various obstetrical complications. At present
      it is utilised in acquired coagulopathy, bleedings, traumatic cases and extensive
      surgical operations especially associated with DIC. We report two cases of severe
      complications during delivery. Both patients had a massive bleeding, severe
      disorders of haemostasis, which on effect were leading to DIC. In therapy a large
      quantity of blood products were applied. Conventional treatment with
      anticoagulant did not give any results. Administration of NovoSeven gave at last
      radical turn in course of treatment and the improvement in patient's state. In
      obstetrical practice NovoSeven is recommendable supplement of conventional
      treatment in severe coagulopathy.

PMID- 14669396
TI  - [HPV infection in pregnant women].
AB  - AIM: Evaluation of incidence of HPV infection in pregnant women. MATERIALS AND
      METHODS: Material consisted of 145 pregnant patients with a range age from 18 to
      37, in 2nd or 3d trimester of pregnancy. The control-group included non-pregnant
      women, participants of preventive skinning programme against cervical cancer, as
      number and age structure as the study group. All patients had cervical specimens
      collected for cytological evaluation. Specimens for HPV testing were taken by
      Digene Sampler Cervical Kit--from cervix and posterior fornix. The presence of
      HPV DNA was detected with the Hybrid Capture II, dividing into 2 groups of high
      and low risk cancer associated types. RESULTS: DNA HPV was detected in 19 (13.1%)
      pregnant women treated in Department of Obstetrics, Gynaecology and Oncology. In
      14 (9.6%) non-pregnant women from control group the Hybrid Capture II test was
      positive. The difference in frequency of infection has not statistical
      significance (Chi 2 = 0.55 alpha = 0.05). Respectively in 11(7.6%) and 8(5.5%)
      patients from I group HPV of high and low risk cancer associated type were
      detected. In II group infection of viruses with high risk was detected in 8
      (5.5%), and with low cancer risk in 6(4.1%) patients. As I group as II group the
      presence of DNA HPV was estimated in younger women. CONCLUSIONS: The pregnancy
      does not seem to be independent factor that increases frequency of HPV
      infections. Despite of changes in hormonal balance and associated with pregnancy
      increase of immunity we have not found statistical significant differences
      between the study-group and control-group. There seem to be in connection with
      changes of sexual behaviour of pregnant women.

PMID- 14669395
TI  - [Morphologic parameters of blood platelets and activity NA+/H+ (NHE-1) exchanger
      in normal pregnancy and pregnancy complicated with preeclampsia].
AB  - The aim of the study was the evaluation of number and morphologic parameters of
      blood platelets and sodium-proton platelet exchangers in pregnant women in the
      3rd trimester of pregnancy, healthy (155) and with preeclampsia (40). RESULTS:
      Blood platelet number was significantly lower in patients with preeclampsia than
      in healthy subjects (195,000 vs 222,000). Mean platelet volume was significantly
      higher in patients with preeclampsia (9.5 fl vs 8.6 fl). The activity of Na+/H+
      was slightly higher in pregnants with preeclampsia.

PMID- 14669397
TI  - [Fetal pulmonary artery blood flow valuation in pregnancies complicated by
      oligohydramnios].
AB  - OBJECTIVES: The objective of the study was to estimate selected Fetal Pulmonary
      Artery blood flow parameters in pregnancies complicated by oligohydramnios in
      relation to normal pregnancies. MATERIALS AND METHODS: A total of 52 patients
      between 26 and 39 weeks of pregnancy complicated by oligohydramnios due to:
      placental insufficiency, PROM or idiopathic etiology and 69 normal pregnancies
      were involved in the study. Ultrasound examination using color and pulse Doppler
      were made. Signal was obtained from distal part of right or left pulmonary artery
      at the level of four chamber view. The RI, PI and S/D ratio were estimated.
      RESULTS: Significant increase in PI was observed in the group with severe
      oligohydramnios (AFI < 2.0 cm) compared to normal pregnancies. No significant
      differences were selected in RI and S/D ratio between mentioned groups.
      CONCLUSIONS: The study showed deterioration in fetal pulmonary artery blood flow
      in pregnancies complicated by severe oligohydramnios.

PMID- 14669398
TI  - [Fetal brain blood flow velocity monitoring in high risk pregnancies].
AB  - OBJECTIVES: Blood velocity in the fetal vein of Galen and straight sinus is
      normally even and without fluctuation. Transverse sinus blood velocity pattern
      shows a characteristic triphasic shape. The aim of this study was to establish
      whether blood flow velocity pulsations in the Galen vein, straight sinus and
      transverse sinus velocimetry in high-risk pregnancies are related to an adverse
      outcome. MATERIALS AND METHODS: The Galen vein, straight sinus and transverse
      sinus were located by color Doppler ultrasound in 110 pregnancies complicated by
      pregnancy-induced hypertension and intra-uterine growth retardation with blood
      velocity recorded by pulsed Doppler. The incidences of blood velocity pulsations
      in Galen vein and straight sinus as well as peak systolic velocity, lowest
      diastolic velocity and resistance index (RI) from transverse sinus were
      correlated to pregnancy outcome, including emergency operative intervention
      and/or neonatal distress. Umbilical artery and venous and uterine and middle
      cerebral artery blood velocity was also recorded at the same time. RESULTS:
      Pulsating blood velocity in the Galen vein and transverse sinus was found in 40
      and 10 cases, respectively. Signs of brain sparing in the middle cerebral artery
      were seen in 23 fetuses. Abnormal values for RI, peak systolic velocity and
      lowest diastolic velocity from transverse sinus were found in 20.6 and 18 cases,
      respectively. Galen vein pulsations were highly significantly related to adverse
      outcome of pregnancy and significantly more frequent in the present study than in
      the umbilical vein. Parameters studied in straight sinus and transverse sinus
      showed poor correlation with outcome of pregnancy. CONCLUSIONS: Venous pulsations
      in the Galen vein are significantly correlated to adverse outcome of high-risk
      pregnancy. Straight sinus and transverse sinus velocimetry was not associated
      with perinatal outcome and might not be useful in predicting fetal distress.

PMID- 14669399
TI  - [Bilateral renal agenesis at the Department for Diagnosis and Prophylaxis of
      Fetal Malformation at the Institute Polish Mother's Memorial Hospital with fetal
      echocardiography in years 1994-2002].
AB  - There was done 8525 sonographical and echocardiographical examinations in 1994
      2002 in the Department for Diagnosis and Prophylaxis of Fetal Malformation
      (DDPFM) of Institute of Polish Mother's Memorial Hospital. In 22 cases (0.25%)
      bilateral renal agenesis (BRA) was diagnosed. Till year 1999 the examinations
      were performed on Acuson 182 XP an since year 2000 on Philips HDI 5000 with Power
      Doppler. In 6 cases (27%) the suspicion of BRA were diagnosed in others places
      and in 16 cases (73%) in DDPFM. The average age of pregnant was 25.5 (+/- 4.8)
      and the average fetal age during first examination at DDPFM 27 weeks and 2 days
      (+/- 5 days). 83% of pregnant were from low risk group. The ahydramnion was the
      most frequent diagnosed anomaly (11 cases) and intrauterine growth retardation
      (IUGR) (4 cases). Till year 1999 BRA was diagnosed based on indirect syndromes:
      lack of visualization of kidney, the absence of bladder, no improvement after
      diagnostic amnioinfusion. Since year 2000 BRA was diagnosed based on indirect
      syndromes and lack of visualization of kidney artery in Power Doppler. In 16
      fetuses there were not abnormality in echocardiographical examination. In 5 cases
      pericardial effusion were diagnosed. In 5 cases cardiomegaly and in 3 cases
      hypertrophy of heart were diagnosed. Among 22 pregnancies there where 8 (36%)
      intrauterine deaths, 1 (5%) fetus was born before 32nd week of gestation and 13
      (59%) died after birth. 12 (55%) fetuses were delivered in I PMMH and 10 (45%)
      cases in others hospitals. In 15 (68%) cases there were vaginal delivery and 7
      (32%) cesarean sections. The average birth weight was 1530 grams and Apgar score
      in 19 newborns was 0-1. CONCLUSIONS: 1. Bilateral renal agenesis is a lethal
      malformation, which can be suspected during screening obstetrical examination
      (ahydramnion, IUGR), but it needs confirmation by genetical ultrasound and
      echocardiographical examination. 2. The mean technique during examination for BRA
      is Power Doppler.

PMID- 14669400
TI  - [Fetal posterior urethral valve (PUV) in database of Department of the Diagnosis
      and Prophylaxis of Congenital Malformation Institute Polish "Mother's Memorial
      Hospital" in 1994-2002 and echocardiographic results].
AB  - OBJECTIVES AND DESIGN: The aim of this study was retrospective analysis of
      ultrasound and echocardiographic examinations in fetuses with diagnosis of
      posterior urethral valve, at the referral center from the database of our unit in
      8 years (1994-2002). RESULTS AND CONCLUSIONS: Among 8525 ultrasound and
      echocardiography examination performed in the Department of the Diagnosis and
      Prophylaxis of Congenital Malformation Institute Polish "Mother's Memorial
      Hospital" the diagnosis of fetal posterior urethral valve was established in 22
      cases. The frequency of premature deliveries was 80% among fetuses with PUV. Over
      54% of all fetuses with PUV demonstrated functional abnormalities in circulatory
      system. 40% of all diagnosed fetuses with PUV survived longer then 6 months after
      delivery. 80% of all fetuses with PUV and functional abnormalities in
      echocardiographic examination died while only 20% of all fetuses with PUV without
      any abnormalities in circulatory system. Echocardiographic examination can be
      helpful in forecasting in utero and post delivery course of fetuses/neonates with
      PUV diagnosis.

PMID- 14669401
TI  - [Neonatal outcome multiple pregnancies at the Neonatal Department of Research
      Institute of Polish Mother's Memorial Hospital].
AB  - OBJECTIVES: The purpose of this study was to analyze the course of neonatal
      period among babies born from truly higher-order multiple pregnancies (> or = 3).
      DESIGN: The retrospective analysis included 81 infants born from multiple
      pregnancies (> or = 3), hospitalized in Neonatal Department of Research Institute
      of Polish Mother's Memorial Hospital between 1995-2001. MATERIALS AND METHODS:
      Studied population contained 63 babies delivered from 21 triplet pregnancies, 8
      newborns from 2 quadruplet pregnancies and ten quintuplets. The groups were
      analyzed according to gestational age, birth weight, ventilation and
      hospitalization time as well as early and late consequences of prematurity.
      RESULTS: Among the multiples (> or = 3) the mean birth weight of triplets,
      quadruplets and quintuplets was respectively: 1656 g vs 1166 g vs 725 g, the
      diminished gestational age was also noticed: 32.4 vs 30 vs 26.5 GA. The cesarean
      section ratio in triplet deliveries was 95%, while quadruplets and quintuplets
      pregnancies were always delivered by operative interventions. The increase in
      number of fetuses was significantly associated with prolonged ventilation time
      (mean 9.5 vs 22.2 vs 57.5 days) as well as the hospitalization (mean 29.1 vs 64.1
      s 79.6 days). The differences between mentioned above values reached statistical
      significance (p < 0.001). One out of three neonates born from triplet pregnancy
      required ventilatory support (36.6%), whereas in quadruplets and quintuplets this
      ratio reached 100%. The respiratory distress syndrome treated with surfactant was
      diagnosed in 7.9% (5/63) of triplets, 37.5% (3/8) quadruplets and 100% of
      quintuplets among whom 8 babies needed more than one dose of surfactant. The
      increased risk of unfavorable prematurity outcome (PDA, ROP, BPD, IVH) and
      neonatal death was highly related to plurality of pregnancy. CONCLUSIONS:
      Multiple pregnancies resulting from infertility treatment cause many medical
      problems. Undesirable outcome among neonates delivered from higher-order multiple
      pregnancies (> or = 3 fetuses) predestine to more judicious approach in the
      application of assisted reproductive techniques and multiple pregnancies
      prophylaxis.

PMID- 14669402
TI  - [Extracellular matrix of the umbilical cord vein in EPH gestosis and fibroblast
      growth factor].
AB  - It was found in our previous studies that EPH gestosis is accompanied by an
      extensive remodeling of the extracellular matrix of the umbilical cord. Studies
      were performed on the umbilical cord veins of 10 control and 10 newborns
      delivered by mothers with EPH gestosis. It was decided to determine umbilical
      cord vein ability to bind of labeled (125J)-basic fibroblast growth factor
      (bFGF), and FGF content by Western immunoblot and ELISA methods. Our experiments
      indicated that the extracts of umbilical cord vein contain endogenous bFGF and
      several soluble FGF-binding compounds of different molecular weight. It is of
      interest that EPH gestosis is associated with a decrease in bFGF content. It
      seems be possible that the decrease of bFGF amount may be one of the factors,
      which constrain the biosynthesis of collagen in EPH gestosis umbilical cord vein
      wall.

PMID- 14669403
TI  - [Immunotherapy as an effective treatment of recurrent spontaneous abortion--own
      experience].
AB  - OBJECTIVES: Recent data emphasize relationship between antiphospholipid
      antibodies (APA) and increased natural killer cell activity in women with
      recurrent spontaneous abortion (RSA). Therefore, it has been proposed that final
      common mechanism involved in the pathogenesis of RSA is associated with auto- and
      alloimmunity. DESIGN: The aim of this study was to present our data concerning
      diagnosis and treatment of women with RSA. MATERIALS AND METHODS: Sixty
      nonpregnant women with the history of RSA were studied, among them 41 were
      screened at the beginning of their next pregnancy. We investigated the existence
      of inherited (deficiencies of protein C, protein S, antithrombin III, a
      resistance to the activated protein C-including Leiden V mutation) or acquired
      thrombophilia (APA-anticardiolipin antibodies, antiphosphatidylserine antibodies,
      lupus anticoagulant). Natural killer cell activity was measured using flow
      cytometry. In addition, the following lymphocytes surface antigens: CD3, CD4,
      CD8, CD16, CD56 were studied using flow cytometry. We also studied the existence
      of autoimmunity: antinuclear antibodies (ANA), antithyroid antibodies (ATA).
      According to presence of auto- or alloimmunity, we introduce immunotherapy:
      intravenous immunoglobulin, alloimmunization, heparin/aspirin, aspirin alone,
      steroids or combine therapy. RESULTS: We determined the existence of
      thrombophilia in 17 women, ANA in 5 women, ATA in 5 women, increased number of NK
      cells in 16 women and increased NK cell activity in 14 women. Forty-one women
      were pregnant and followed up during pregnancy, among them 33/41 delivered normal
      healthy baby, 7/41 experienced the next abortion and 1/41 had ectopic pregnancy.
      Therefore, overall success of immunotherapy was 80.5%. CONCLUSIONS: Immunotherapy
      seems to be effective treatment for women with the history of RSA and combined
      immune abnormalities. Regulation of immune system activity may underlie possible
      effect of such therapy.

PMID- 14669404
TI  - [Non-immune hydrops fetalis--prognostic factors based on fetal echo (analysis in
      230 cases)].
AB  - OBJECTIVES: The aim of the research was to assess whether all reasons of NIHF
      were leading to the same poor outcome. MATERIALS AND METHODS: The material of the
      research study consisted of 192 fetuses with follow up from 230 fetuses with NIHF
      who had echocardiography and detailed sonography between 1992 and 2002. RESULTS:
      The most common anomalies associated with NIHF were cardiological anomalies n =
      71 (30.8). The remain extracardiac causes of NIHF were: so called "other
      structural defects" n = 24 (10.4%), infections (without myocarditis) n = 24
      (10.4%), multiple structural defects n = 20 (8.7%), urogenital defects n = 17
      (7.4%), pulmonary anomalies n = 17 (7.4%), gastrointestinal anomalies n = 12
      (5.2%), chromosomal defects n = 8 (3.5%), mirror syndrome n = 2 (0.9%) and
      idiopathic n = 35 (15.3%). In the group of NIHF 102 fetuses (44.3%) presented
      echocardiographic signs of congestive heart failure which statistically increased
      mortality ratio. In the group of fetuses with NIHF follow up was established in
      192 (83.4%) fetuses/newborns; there were n = 139 (72.4%) demise and n = 53
      (27.6%) alive. Therapy in utero was applied to 28 cases. In this group 13
      fetuses/newborns (46.4%) survived. CONCLUSIONS: Multiple structural anomalies and
      cardiological anomalies causing NIHF are connected with poor prognosis for fetus
      or neonate. Congestive heart failure coexisting with NIHF (in our series in about
      44%) significantly increased mortality ratio what point the special role of fetal
      echocardiography. Relatively better prognosis was observed possible in cases with
      NIHF without structural anomalies and mild intensify or due to infection but
      without cardiac anomalies. In selected fetuses therapy in utero may increase the
      survival ratio.

PMID- 14669405
TI  - [Impact of threatened preterm labor and lower genital tract biocenosis on the
      concentrations of selected proinflammatory cytokines in cervicovaginal fluid of
      pregnant women].
AB  - AIM: Recent studies have suggested that proinflammatory cytokines might play a
      crucial role in the mechanism of preterm labour and delivery. Lower genital tract
      infection could also influence the cytokines levels. The main aim of this study
      was to compare the concentrations of interleukin (IL)-1 alpha, IL-1 beta, IL-6
      and IL-8 in cervicovaginal fluid of pregnant women with threatened preterm labour
      (TPL) with group of women with normal course of pregnancy (reference group) and
      to determine impact of lower genital tract microflora on cytokines concentration.
      MATERIAL AND METHODS: Cervicovaginal fluids were obtained by lavage from 40
      pregnant women at 22 to 34 weeks' gestation. Those samples were analyzed for the
      concentrations of selected cytokines using standard enzyme-linked immunosorbent
      assay technique. Lower genital tract microbiology was diagnosed using Gram stain
      method according to Spiegel's criteria. TPL was defined as uterine contractions
      treated by tocolysis. RESULTS: Threatened preterm labour (TPL) was diagnosed in
      22 (55.0%) cases. Mean gestational age at the time of cytokines measurement was
      28.6 weeks. Mean concentrations of IL-1 alpha, IL-1 beta and IL-8 measured in
      cervicovaginal fluid of pregnant women with TPL and in reference group were
      similar (89.43 vs. 91.17 pg/ml; 42.05 vs. 41.01 pg/ml and 621.8 vs. 697.8 pg/ml,
      respectively). Vaginal levels of IL-6 was higher among women with preterm labour
      (21.1 pg/ml vs. 13.9 pg/ml) as compared to reference group. Bacterial vaginosis
      (BV) was diagnosed in 11 women (27.5%) while grade I microflora in 19 (47.5%).
      There was a positive correlation between BV and IL-1 alpha and IL-1 beta
      concentration but no with IL-6 and IL-8. CONCLUSIONS: Vaginal levels of IL-6 were
      found to be significantly elevated among women with threatened preterm labour
      while IL-1 alpha and IL-1 beta among women with BV. The usefulness of cytokines
      measurement in cervicovaginal fluid of pregnant women for prediction of preterm
      delivery should be clarified in further after excluding the impact of lower
      genital tract infections on cytokines concentrations.

PMID- 14669406
TI  - [Urinary iodine excretion and thyroid function in pregnant women of Bydgoszcz
      District prior to and after the introduction of iodized salt].
AB  - INTRODUCTION: Before the introduction of the kitchen iodized salt in 1997 Poland
      was an area of mild and moderate iodine deficiency. AIM: The aim of the study was
      to determine the degree of iodine deficiency and thyroid function in pregnant
      women prior to and after the introduction of iodized salt. MATERIAL AND METHODS:
      Iodine urinary excretion and serum levels of TSH, fT3 and fT4 were determined in
      pregnant women divided into the two groups--with and without iodine
      supplementation. RESULTS: Before the introduction of the kitchen iodized salt
      iodine urinary excretion in pregnant women was 70.46 +/- 43.99 micrograms/l. The
      introduction of kitchen iodized salt increased iodine urinary excretion to 92.23
      +/- 42.14 micrograms/l (p < 0.01). In pregnant women with iodine supplementation
      serum levels of TSH and fT3 were reduced. CONCLUSIONS: 1. There was a mild iodine
      deficiency in pregnant women before the introduction of the kitchen iodized salt
      programme. 2. The kitchen iodized salt increased iodine urinary excretion rates,
      3. Reduced levels of serum TSH and fT3 after the introduction of iodized salt
      indicate diminished thyroid stimulation in pregnant women with higher iodine
      intake.

PMID- 14669407
TI  - [Total antioxidative activity measured by ABTS method in pregnant women treated
      with L-arginine for IUGR].
AB  - Elevated concentration of free radicals is observed in IUG and it is connected
      with high rate of prematurity and perinatal mortality too. The total
      antioxidative serum activity is one of the oxidative stress defence system
      parameter. The main aim of the study was to find the correlation between the L
      arginine therapy and total antioxidative concentration. MATERIAL AND METHODS: The
      study was done in Dep. of Obstetrics and Gynaecology Medical University in Lodz
      in 2000-20003 y. The study group consist of 45 women with ultrasound diagnosed
      IUGR, the control group consist of 30 healthy pregnant women at the same
      gestational age. The IUGR therapy consist of L-arginine 3 x 1 g oral dose daily.
      The total antioxidative activity was measured in maternal blood on first and 20
      th day of treatment. The Wayner method was used to measure total antioxidative
      activity by reduction of ABTS. The results were expressed in microM of serum.
      RESULTS: The value of the total antioxidative activity at the first day of
      observation in women with IUGR was 225.9 microM and after 20 days increased to
      231.8 microM. In women in normal pregnancy at the first day the value was 249.6
      ng/ml microM and after 20 days of observation 247.8 microM. CONCLUSIONS: The
      total antioxidative activity in blood serum decreased in pregnancy connected with
      IUGR. The L-arginine treatment decreased the oxidative stress risk.

PMID- 14669408
TI  - [Analysis of 8-isoprostane concentration as a marker of oxidative stress in
      pregnant women diagnosed with IUGR].
AB  - Intrauterine growth restriction is connected with high rate of prematurity and
      perinatal mortality. 8-isoprostane is one of the oxidative stress indices,
      similar to the prostaglandins and connected with vessels restriction. The main
      aim of the study was to find the correlation between the L-arginine and
      acetylsalicylic acid therapy and 8-isoprostane concentration. MATERIAL AND
      METHODS: The study was done in Dep. of Obstetrics and Gynaecology Medical
      University in Lodz in 2000-2002 y. The study group consist of 50 women with
      diagnosed IUGR, the controls: 30 healthy pregnant women at the same gestational
      age. The IUGR therapy consisted of L-arginine 3 x 1 g and acetylsalicylic acid-
      Acard 1 x 1 daily. 8-isoprostane was measured in maternal blood in first and 20
      th day of observation. The Oxis Immunoassay for 8-epi prostaglandin was used. The
      results were expressed in ng/ml of serum. RESULTS: The concentration of 8
      isoprostane at the first day of observation in women with IUGR was 0.0587 ng/ml,
      and after 20 days decreased to 0.0569. In women in normal pregnancy at the first
      day was 0.0539 ng/ml and after 20 days 0.0547 ng/ml. CONCLUSIONS: The 8
      isoprostane concentration increased in blood serum due to the pregnancy duration.
      The therapeutic method decreased the concentration of this oxidative stress
      marker.

PMID- 14669409
TI  - [Enzymatic diagnosis of neurological risk of premature labor].
AB  - The level of oxytocinase in the pregnant woman's blood is a sensitive marker of
      the efficiency of the hypothalamus/hypophisis/suprarenal glands in mother and
      fetus, as well as the quantity of hormone production, also in placenta, which
      determines the duration of pregnancy and the course of labor. In the study, the
      level of oxytocinase was measured before the labour in 485 pregnant women at risk
      of premature labour. After the mean duration of pregnancy of 264 +/- 12 days, 353
      infants were born fully mature (group I), and 132 with the lowered maturity of 6
      9 Klimek points (group II). In group II, the mean pregnancy duration (249 days),
      body mass (2700 g) and oxytocinase level (5.6 mumol/l/min) were significantly
      lower and tocolysis was necessary twice as often (41% vs. 21%). Independently of
      the level of newborn maturity in cases of tocolysis the mean level of oxytocinase
      was significantly 2.6 times lower (3 +/- 0.8 mumol/l/min) than in the other
      pregnant women (7.9 mumol/l/min). It proves, that low oxytocinasaemia becomes
      normal following the ACTH-depot therapy, which eliminates the necessity of
      tocolysis.

PMID- 14669410
TI  - [Life threatening conditions in premature infants].
AB  - The aim of the study was to analyze life-threatening conditions of the premature
      neonates who required hospitalization in The Neonatal Intensive Care Unit (NICU).
      Postnatal mortality was also taken into consideration. MATERIAL AND METHODS: The
      study group consisted of the neonates born prematurely in the Obstetrics and
      Gynecology Clinic of Medical University in Warsaw in the period from 1st January,
      2002 to 31st December, 2002. Birth weight, gestational age, reasons of
      respiratory insufficiency, co-existing diseases, complications and causes of
      postnatal death were analyzed. RESULTS: 44 out of 174 prematures were admitted to
      NICU because of the necessity of mechanical ventilation. There were several main
      pulmonary reasons of respiratory insufficiency: respiratory distress syndrome,
      primary pneumonia, and transient tachypnoe of neonates. Primary infection was the
      most frequent co-existing problem. The serious complications of the prematurity
      included retinopathy and persistent arterial duct (requiring surgical
      procedures). All deaths in the study group were noted in infants with birth
      weight below 1250 g. CONCLUSIONS: Prematurity and its complications were the main
      causes of life-threatening conditions in newborns that lead to hospitalization in
      NICU. The postnatal mortality rate was the highest in premature neonates with
      birth weight below 1000 g (33.3%).

PMID- 14669412
TI  - [Doppler measurements of blood flow in the middle cerebral artery for the
      diagnosis of fetal anemia].
AB  - OBJECTIVES: This paper presents a possibility of non-invasive diagnosis of fetal
      anemia based on the Doppler assessing of peak systolic velocity (PSV) in the
      fetal middle cerebral artery. The results of Doppler measurements were compared
      with fetal peripheral blood count estimated after cordocentesis. MATERIALS AND
      METHODS: Doppler measurements of blood flow velocity in the fetal middle cerebral
      artery were performed in years 2000 and 2001 in 22 pregnancies complicated by
      maternal blood group alloimmunisation. Gestation age varied from 27 to 36 weeks,
      the mean gestation age was 32 weeks. Depending on hemoglobin concentration in the
      fetal blood sample the severity of anemia was divided into three groups: severe
      anemia (Hb = < 7 g%), middle (Hb = = 8-10 g%) and light (Hb = = 10-12 g%). The
      fourth group consisted of fetuses without anemia (Hb > 12 g%). The results were
      statistically analyzed to estimate correlation between the Doppler blood flow
      indexes (PI, RI, SD and PSV) in the middle cerebral artery and the peripheral
      blood count (Hb, Ht, erythrocyte count) of fetal blood received by cordocentesis.
      Using T-Student-test the differences of average maximal blood flow velocities and
      mean Doppler indexes in the group of fetuses with severe anemia (Hb < 7 g%) and
      fetuses without anemia (Hb > 12 g%) were compared. RESULTS: Highest (negative)
      correlation was found between the peak systolic velocity and the fetal hemoglobin
      concentration. The correlation index was -0, 85, which means the higher the peak
      systolic velocity the lower the hemoglobin concentration. The difference between
      the mean peak systolic velocity in the group of fetuses with severe anemia and
      the group without anemia was statistically significant (p < 0.001). However,
      there was no statistical significant difference in the mean peak systolic
      velocity between the group with middle anemia (Hb = 10-12 g%) and the group
      without anemia (Hb > 12 g%). CONCLUSIONS: Doppler ultrasonography with the
      measurement of peak systolic velocity in the middle cerebral artery is a good
      method in evaluating of fetal peripheral blood count. Non-invasive peak systolic
      velocity measurements in the middle cerebral artery allow to assess the fetal
      hemoglobin concentration and also to reduce the count of diagnostic
      cordocentesis.

PMID- 14669411
TI  - [Effectiveness of passive immunisation against respiratory syncytium virus in a
      group of premature infants with birth weight below 1000 grams].
AB  - Respiratory syncytial virus (RSV) is a major cause of respiratory tract infection
      during the child's first year of life. Those who survive neonatal intensive care
      are commonly rehospitalized. In the absence of vaccine, passive immunoprophylaxis
      is the preferred approach. Safety and efficacy of Palivizumab (Synagis) was
      proven in the Impact-RSV Trial, conducted in the USA, Canada and UK. The aim of
      the study was to determine efficacy of humanized monoclonal RSV antibody in
      prematures infants born 25-32 week gestation with weight birth below 1000 g with
      and without broncho-pulmonary dysplasia. We compared the hospitalization rates
      and morbidity between two groups of children who received palivizumab and without
      any protection. We confirm the efficacy and safety of Synagis. The outcome of
      this study supports the use of palivizumab prophylaxis in high-risk children.

PMID- 14669413
TI  - [Thyroid dysfunction in pregnant women and correlation with clinical and
      metabolical status of their newborns].
AB  - The idea of our work were to estimate the function of thyroid in newborns and
      their mothers in the group of pregnant women with thyroid disturbances. We
      examined 38 pregnant women and their newborns. We confirmed that diabetes
      appeared more frequently in all cases. The mean gestational age of newborns was
      39 weeks. The cesarean sections were performed more frequently in the group of
      mothers with Graves-Basedow disease. The general condition of newborns after
      delivery were assessed as good acc. Apgar score. The newborns from pregnancies
      complicated with Graves-Basedow disease in majority cases were dystrophic.

PMID- 14669414
TI  - [Epidural analgesia during labour with a singleton alive fetus at term].
AB  - OBJECTIVE: Whether epidural analgesia (e.a.) have influence on the way of
      delivery, indications to cesarean section (c.s.) and neonatal outcome. MATERIAL
      AND METHODS: We have analysed 8784 deliveries. We excluded women with plural
      pregnancy, pre-term parturitions, elective c.s., still births. Finally we studied
      339 parturitions with e.a. versus 6868 the others and theirs newborns. RESULTS:
      More frequent c.s. was in women with e.a. (18.6% vs 7.9%; p < 0.001) or forceps
      (f.d.) (7.7% vs 3.5%; p < 0.005). Among those with e.a. the most frequent
      indications to c.s. were labour with no progression (23.4% vs 4.0%; p < 0.001)
      and the others as hypoxia fetus (68.7% vs 82.6%; p < 0.01). The lost of blood
      with oblique to transfusion was more frequent at f.d. at comparison to c.s. and
      spontaneous delivery (26.9% vs 3.2% and 6.8%; p < 0.001). The condition of
      neonates at 1 min. according Apgar score was the worse after f.d. in comparison
      to spontaneous delivery (7.38 +/- 2.22 vs 8.79 +/- 1.41 points; p < 0.005) and
      after c.s. (7.38 +/- 2.22 vs 8.55 points; p < 0.05). In comparison the state at 5
      min. was the similar after f.d. (9.11 +/- 1.24 vs 9.53 +/- 0.81 points; p = 0.05)
      and (9.11 +/- 1.24 vs 9.48 +/- 0.83 points; p = 0.09). CONCLUSIONS: Women with
      epidural analgesia more frequent were ending the delivery by cesarean section or
      forceps. The forceps delivery was related with worse neonatal outcome at first
      minutes of live, and bigger lost of blood during labour. Epidural analgesia
      predisposed to cesarean section delivery caused of partus without progress and
      relatively deminished caused by fetus hypoxia.

PMID- 14669415
TI  - [Pregnancy and delivery after hysteroscopic metroplasty].
AB  - AIM OF THE STUDY: Outcomes of treatment of habitual miscarriages and course of
      pregnancy and delivery in women after hysteroscopic metroplasty i.e.
      hysteroscopic resection of uterine septum. MATERIAL AND METHODS: Material
      consisted of 31 women with uterine septum operated between years of 1995-2002
      because of habitual miscarriage by surgical hysteroscopic technique. The control
      group consisted of 26 women treated between years of 1990-1997 by Strassman's
      operation. Outcomes of treatment of habitual abortions, course of pregnancy and
      delivery were analyzed in both groups. The statistical analysis was performed by
      Chi 2 test (p < 0.05). RESULTS: After such treatment 27 out of 31 hysteroscopic
      treated women became pregnant. In first pregnancy in 12 women miscarriages and in
      3 cases premature delivery were observed. Twelve pregnant women delivered
      pregnancy till 37 week. 15 infants survived (3 premature baby). Out of 26 women
      in control group after Strassman's operation 24 became pregnant, but 12 had
      miscarried. All pregnancy in control group i.e. ten mature pregnancy and 2 during
      premature delivery were ended by Cesarean section. The efficacy of treatment of
      habitual miscarriage due to uterine septum by hysteroscopic surgery was 55.5%,
      and there was no statistical significant difference between hysteroscopic surgery
      and Strassman's operation (50.0%). CONCLUSIONS: On the basis of result obtained
      the hysteroscopic metroplasty should be method of choice in the treatment of the
      uterine septum. Although the vaginal delivery is preferred one should have in
      mind the late complications of hysteroscopic surgery.

PMID- 14669416
TI  - [Evaluation of the morphology of the human placental cotyledon following dual in
      vitro perfusion in variable magnetic field].
AB  - Objectives and the aim of the study was electron-microscopy morphological
      estimation of the human placental cotyledon after 180 minutes of dual closed
      perfusion in vitro. MATERIALS AND METHODS: In the experimental group the
      cotyledons were exposed to variable magnetic field of 2 mT magnetic induction and
      50 Hz frequency. The control group K (10 perfusions) was not subjected to
      magnetic field while the experimental group B (10 perfusions) was influenced by
      magnetic field. RESULTS: It was found that homogeneous variable magnetic field
      disturbs the ultrastructure of the nuclei and cytoplasma and it increases the
      density of the vascular-epithelial membrane of villi cells of human placenta in
      vitro. CONCLUSION: Variable sinusoildal, magnetic field of 2 mT magnetic
      induction and 50 Hz frequency disturbs the ultrastructure of the nuclei and
      cytoplasma and it increases the density of the vascular-epithelial membrane of
      villi cells of human placenta in vitro after 180 minutes of dual closed perfusion
      in vitro.

PMID- 14669417
TI  - [Characteristic of affective disorders of the first week of puerperium].
AB  - Prospective studies ware carried in 200 lying-ins. To diagnose affective
      disorders medical interview and anonymous questionnaire BDI and EPDS were used.
      During interview 31% showed baby-blues. Signs of postpartum depression occurred
      in 18.5% women. No case of psychosis as well as critical incident of stress
      debriefing were stated. Recapitulating postpartum affective disorders occurred in
      49.5% of examined group. Among negative psycho-socioeconomic factors pathological
      course of pregnancy in 14%, incorrect relationship with parents in 9%, low
      material status in 7%, unemployment in 32% and unwanted pregnancy in 3% of women
      were observed. Affective disorders in lying-ins women with postpartum depression
      are correlated with occurring of least 3 of above-mentioned factors. Baby-blues
      was found in 31%, while signs of depression were found in 17-20% of women during
      first week of puerperium. Existence of at least 3 negative psycho-socioeconomic
      factors during pregnancy or labour correlates with appearance of postpartum
      depression.

PMID- 14669418
TI  - [Pregnancy and delivery course in patients with gestational diabetes mellitus].
AB  - OBJECTIVES: The aim of the study was to assess mother and fetal outcome in
      gestational diabetic women. MATERIALS AND METHODS: The study covered 689 patients
      with gestational diabetes mellitus. All women had been taken care of II
      Department of Obstetrics and Gynecology Warsaw Medical University in 1997-2001
      years. The following parameters were analyzed: the patients ages, past obstetric
      experience, gestational age of GDM diagnosis, pregnancy complications, delivery
      course and neonatal outcomes. RESULTS: Among study group 11.9% patients required
      insulin to maintain blood glucose concentration in normal range. GDM was mostly
      (44.1%) diagnosed between 29 and 34 weeks of pregnancy. At the recommended
      gestational age of screening tests--24-28 weeks--there were detected only 33.4%
      GDM. The most frequent pregnancy complication was imminent preterm delivery
      (16.7%). Delivery at term occurred of 89.1% of cases. Percentage of preterm
      deliveries was 10.9%. Spontaneous vaginal deliveries were the most frequent
      (72.5%). 23.2% women were delivered by Cesarean section. The most frequent
      indication of surgical labor were the symptoms of intrauterine fetal asphyxia
      (35.6%) and cephalo-pelvic disproportion (26.3%). Most of the newborn (83.3%) had
      normal birth weight between 2500 g and 4000 g. Among infants the most frequent
      complications were: hyperbilirubinemia (17.3%) and hypoglicemia (15.6%).
      Intranatal death occurred in 0.1% of cases, whereas neonatal death--0.4%.
      Congenital defects were found in 4.3% of all offspring. The most frequent
      congenital malformation was heart defect--1.3% of newborns (almost half of all
      congenital defects) CONCLUSIONS: Early diagnosis of gestational diabetes mellitus
      and specialists obstetric surveillance prevent of pregnancy complications and
      perinatal mortality, morbidity.

PMID- 14669419
TI  - [Umbilical cord complications in twin pregnancies].
AB  - OBJECTIVES: The postpartum umbilical cord examination can provide a lot of
      significant information concerning discordant twin growth or reasons of
      intrauterine death of one or all the fetuses. The aim of this study was the
      postpartum assessment of umbilical cords in twin pregnancies. MATERIAL AND
      METHODS: The examination material consisted placentas coming from 110 twin
      pregnancies. The analysis concerned the assessment of placenta types, the
      umbilical cords attachment place and also the twins birth weight. RESULTS: Basing
      on the studies of placentas coming from 110 twin pregnancies 76 (69.0%)
      dichorionic and 34 (31.0%) monochorionic placentas were found. Among dichorionic,
      40 (53%) separated and 36 (47%) fused placentas were observed. Among
      monochorionic 31 (91%) diamniotic and 3 (9.0%) monoamniotic placentas were
      present. Abnormal umbilical insertion to placenta was most frequently observed in
      monochorionic pregnancies: in diamniotic--marginal insertion in 21.2%,
      velamentous insertion in 15.9%, and in monoamniotic--equally 33.3%. In
      dichorionic pregnancies, for fused placentas--marginal in 8.7%, velamentous in
      9.1%, and for separated--5.6% and 3.1%. CONCLUSIONS: The abnormal umbilical cord
      insertions to the placenta was most frequently found in monochorionic
      pregnancies. Among pairs of twin born with body weight discordance, the abnormal
      umbilical cord insertion was more frequently found in the case of the smaller
      newborn.

PMID- 14669420
TI  - [Treatment outcome in women suffering from recurrent miscarriages and
      antiphospholipid syndrome].
AB  - OBJECTIVE: To evaluate the outcomes of treatment in patients suffering from
      recurrent spontaneous abortion and antiphospholipid syndrome. MATERIALS AND
      METHODS: 148 observed women suffering from recurrent abortion with presence of
      lupus anticoagulant antibodies (LA) and/or high moderate concentration of
      anticardiolipin antibodies (ACA) have been divided randomly into followed three
      treated groups: I--56 patients treated by low-dose of acetylsalicylic acid (LDA,
      75 mg daily); II--39 patients treated by low molecular weight heparin (applied in
      dose of 20 g daily); III--53 patients treated by LDA and low molecular weight
      heparin simultaneously. RESULTS: It has been affirmed that coincidental
      application of low-dose of acetylsalicylic acid and low molecular weight heparin
      statistically more often increase the percentage of successful pregnancy in
      comparison with application of low molecular weight heparin or acetylsalicylic
      acid alone. In the group where only low-dose of acetylsalicylic acid was applied
      the success of pregnancy equaled 89.3%, in the group where only low molecular
      weight heparin was applied the successful pregnancy equaled 81.1% and in the
      group with acetylsalicylic acid and low molecular weight heparin being applied
      together the successful pregnancy equaled 92.5%. In has simultaneously been
      affirmed that the percentage of pregnancy loss is statistically higher in the
      women suffering from isolated occurrence of lupus anticoagulant antibodies
      (21.2%) in comparison with the women suffering from occurrence of anticardiolipin
      antibodies (6.7%) and anticardiolipin antibodies with lupus anticoagulant
      antibodies simultaneously. CONCLUSION: 1. Simultaneous application of low-doses
      of acetylsalicylic acid and low molecular weight heparin seems to be the best
      solution in patients suffering from recurrent spontaneous abortion and
      antiphospholipid syndrome. 2. The occurrence of anticardiolipin antibodies in the
      serum of blood in patients suffering from antiphospholipid syndrome is a better
      foretelling factor for the future pregnancy outcome than the occurrence of lupus
      anticoagulant antibodies.

PMID- 14669421
TI  - [Prevalence of group B streptococcal colonization in pregnant women and their
      newborns based on the results of examination of patients in the Obstetric and
      Gynecology Department of the National Research Institute of Mother and Child--a
      pilot study].
AB  - Group B streptococcus is a main cause of perinatal infections and neonatal
      sepsis. In Poland there is no epidemiological data of the prevalence group B
      streptococcal colonization in pregnant women and the risk for their newborns.
      OBJECTIVES: The aim of the study is to define the prevalence of streptococcal B
      colonization in pregnant women and their newborns. MATERIALS AND METHODS: The
      pregnant women and their newborns from Obstetric and Gynecology Department of
      National Research Institute of Mother and Child were included to our study during
      2001 and 2002 years. Cervical, vaginal and perianal swab were obtained. Women
      with positive cultures were treated with antibiotic during labor. The external
      swabs of their neonate were obtained. RESULTS: 1678 pregnant women took part in
      our study. The GBS (streptococcus agalactiae) colonization was found in 331
      women. The prevalence of pregnant women group B streptococcal colonization in the
      study is 19.7%. 70 of 203 neonates form mothers with positive results of our
      screening, had the GBS colonization confirmed. The prevalence of confirmed
      streptococcal colonization in neonates was 34.5%. One newborn developed early
      onset neonatal sepsis, during the study period. CONCLUSIONS: The prevalence of
      pregnant women group B streptococcal colonization about 20%. For the prevention
      of newborns intrapartum infections a major thing is the prevalence of the
      transmission risk to newborns from mothers with a GBS colonization and the
      appropriate intrapartum management.

PMID- 14669422
TI  - [Influence of interleukin-1 and interleukin-6 on modulation of hypothalamo
      pituitary-adrenal axis in pregnancy at term and in spontaneous and oxytocin
      induced delivery].
AB  - OBJECTIVES: During the pregnancy the placenta and hypothalamus produce trophic
      hormones for hypothalamo-pituitary-adrenal axis (HPA), i.e. corticotropin
      releasing hormone (CRH) and adrenocorticotropin (ACTH). The HPA axis of pregnant
      women is differentially modulated in comparison to non-pregnant ones. Beside
      steroids, the influence on CRH release may be modulated by cytokines, especially
      interleukin 1 (IL-1) and interleukin 6 (IL-6). DESIGN: To evaluate the effects of
      IL-1 and IL-6 on modulation of HPA axis in pregnancy, we have examined the group
      of women with spontaneous delivery, and second group consists of women delivered
      after intravenous oxytocin infusion. All women were at term and in the same
      pregnancy age. MATERIAL AND METHODS: Blood was sampled from a maternal peripheral
      vein days before labour, during the second stage of labour and on the second
      postnatal day, the levels of IL-1, IL-6, CRH, ACTH and cortisol were measured.
      The concentrations of hormones were measured using RIA method. RESULTS: The level
      of IL-1 before the delivery was significantly higher in the group with oxytocin
      induction. CRH concentration before the labour was much higher in the group with
      spontaneous contractions. The levels of IL-1 and CRH in both groups decreased
      during the labour and were lowest after the delivery. Concentration of IL-6 did
      not changed dependently of group and time of blood sampling. Changes in CRH in
      time concentration did not correlate with changes in ACTH levels. ACTH
      concentrations were similar in both groups, low before delivery raised during the
      delivery and low again after labour. Cortisol concentration in spontaneous labour
      was much lower before delivery in comparison with second examined group, then
      lowered during and after the delivery. In group with oxytocin induction, cortisol
      levels raised during the delivery and maintained almost the same level after the
      labour. The time-changes in IL-1 concentration and ACTH and cortisol levels were
      similar in shape in group with spontaneous delivery. CONCLUSIONS: These results
      suggest that IL-6 is not involved in modulation of HPA axis in pregnancy at term.
      IL-1 may modulate mother's HPA axis, influencing the release of ACTH and
      cortisol, probably via stimulation of hypothalamic CRH.

PMID- 14669423
TI  - [Maternal serum concentration of corticotropin releasing hormone (CRF) as a
      marker of preterm labor].
AB  - There is still an urgent need for obstetricians to develop new, noninvasive,
      accurate methods of diagnosing preterm labor. The purpose of this study was to
      evaluation of maternal serum corticotropin-releasing factor concentrations and
      its concentration with onset of labor. The analysis was undertaken of women
      hospitalized in Research Institute Polish Mother's Memorial Hospital-Clinical of
      Perinatology (2001-2002) year with pregnancy between 16 to 35 weeks. All
      pregnancies were singleton gestation free of medical complications but with
      threatened labor. Maternal peripheral blood samples were obtained from
      antecubital vein during the first day of hospitalization. The control group
      consisted of 77 pregnant who delivered term infants whose growth was appropriate
      for gestational age. The study group consisted of pregnant women who gave preterm
      delivery. The serum CRF concentrations were measured using EIA method. Maternal
      serum CRF concentration in control group was 7.28 +/- 1.92 ng/ml. The material
      was obtained in 26.2 +/- 4.5 week of gestation. CRF concentration in studied
      group was 6.37 +/- 1.86 ng/ml +/- and the serum was obtained in 24.3 +/- 4.9
      ng/ml weeks of gestation. The results were paradoxically significantly higher in
      control group. CONCLUSIONS: Our results were not in agreement with the findings
      of other investigators.

PMID- 14669424
TI  - [Correlation between cordocentesis performed during pregnancy and premature
      delivery].
AB  - OBJECTIVES: Cordocentesis is a procedure used to obtain fetal blood sample or to
      perform an intrauterine therapy. The cordocentesis is performed to determine the
      blood group, blood cell counts, fetus karyotype, intrauterine infection, level of
      17-OH progesterone and fetus renal secretion. Access to the umbilical vein is
      possible from the 16-18th week of gestation. DESIGN: The aim of our study was to
      determine the impact of cordocentesis on the premature delivery. MATERIAL AND
      METHODS: Authors have analysed the course of gestation and delivery in all the
      cases with at least one cordocentesis carried out in the Department of Obstetrics
      in Gdansk in 1991-2002. The group of 145 pregnant women was analysed. In this
      group 199 cordocenteses were performed. In 31 cases there was a premature
      delivery which was not a complication of cordocentesis. The duration of
      pregnancies in each group was compared to the control group--a total of 1657
      patients who gave births in the Institute of Obstetrics and Gynecology in 1998.
      For statistical analysis of the results the T-Student test was used with the
      significance level p = 0.05. RESULTS: The mean duration of pregnancy in the
      control group was 40 +/- 2.47 weeks (from 23 to 45), in the group of patients
      after cordocentesis--33.97 +/- 4.68 weeks (from 23 to 42)--no statistical
      difference was found. In the group of patients with lethal malformation of foetus
      the induction of delivery was performed in the 30.97 +/- 4.66 week of gestation
      (from 23rd to 41st)--statistical difference to the group of all patients after
      cordocentesis. In cases with only diagnostic cordocentesis the delivery took
      place in 36.85 +/- 2.60 weeks of gestation and in the group with fetal blood
      transfusions the mean duration of pregnancy was 35.36 +/- 3.72 weeks. The
      incidence of the premature deliveries in the control group was 7.18% and in the
      group of patients after cordocentesis--72.46%--there is significant difference
      between these two groups. The cesarean section was performed in the control group
      in 23.60% and in 36.23% in the group of patients with performed cordocentesis.
      CONCLUSIONS: The intrauterine transfusions during cordocentesis do not influence
      the term of delivery. The term of delivery after the diagnostic and therapeutic
      cordocenteses does not statistically differ from the term of delivery in the
      control group. The cordocentesis (the result of blood tests) allows to determine
      the need of induction of delivery. It gives better prognosis for the newborn.

PMID- 14669426
TI  - [Pregnancy and delivery in women with congenital heart disease].
AB  - OBJECTIVES: Perinatal care of women with congenital heart disease is very
      important for obstetrician. DESIGN: The purpose of this study was to analyse the
      course of pregnancy, delivery and after birth period of women with congenital
      heart disease. MATERIAL AND METHODS: A group of 35 pregnancies and deliveries in
      patients with congenital heart disease cured in 1998-2003 in the Department of
      Obstetrics and of Medical University in Gdansk were analysed. The control group
      was a total of 1657 deliveries in the Department of Obstetrics in the 1998. For
      statistical analysis of the results the T-Student test was used with the
      significance level p = 0.05. RESULTS: Time of pregnancy, birth weight and length
      were statistically different to the control group. CONCLUSIONS: We found no
      cardiological complications during pregnancy in patients with congenital heart
      disease at I and II stage NYHA. Time of pregnancy, birth weight and length were
      statistically different to the control group.

PMID- 14669425
TI  - [Pregnancy, delivery and puerperium in patients after liver transplantation].
AB  - We report two cases of successful pregnancies in women after liver
      transplantation for end-stage liver dysfunction caused in one case by Wilson
      disease and in the second one by lupoid hepatitis. For woman with the Wilson
      disease it was a second pregnancy and for woman with lupoid hepatitis it was the
      first pregnancy. Mothers continued immunosuppressive therapy during their
      pregnancies. Labours started spontaneously at 39th and 36th week's of gestation.
      As a result the healthy two female infants weighing 3600 g and 2420 g
      respectively were born. The first woman with her baby was discharged from
      hospital on the third day after delivery and the second one and her baby on the
      sixth day after delivery. Both were in good condition.

PMID- 14669427
TI  - [Nosocomial infections in a neonatology department, 1995-2002].
AB  - Nosocomial infections in newborns department are common due to number of invasive
      diagnostic and therapeutic procedures, prolonged hospitalization and development
      antibiotic resistance culture. Sepsis achieved 1 to 8 newborn infants for 1000
      live births. This is still unresolved very important medical, organization,
      ethical and medical problem. The aim of this study was the estimation on the
      number, etiology and clinical form of nosocomial infection in Neonatology
      Department as well as the way of spread. We analyzed nosocomial infection in 8770
      newborn infants in Neonatology Department with Intensive Therapy Chair and Clinic
      Obstetric and Perinatology Pomeranian University of Medicine from 1995 to 2002.
      For this retrospective study we used data from Commission for Nosocomial
      Infection. In analyzed period total percentage of newborn infants with nosocomial
      infection was under 1%, but in NICU was over 11%. Inborn vertical infection was
      26.8% and horizontal strictly nosocomial infection was diagnosed in 73.2%.
      Etiology was mainly due to Gram negative bacterial infection. Clinically sepsis,
      pneumonia and meningitis was diagnosed. Clinical manifestation and laboratory
      tests like CRP, PCT, blood count, leukocyte index and microbiological culture was
      used for diagnosis. The most often positive bacterial culture was obtained from
      cock, washstand, bath and medical staff. Nosocomial infections in neonatology
      department are significant medical problem which need continuous monitoring,
      systemic prevention and in case of infection early intervention.

PMID- 14669428
TI  - [Is the mother's bacterial vaginosis with PROM a significant factor for
      intrauterine infection of the fetus in preterm labor before 32 weeks of
      gestation].
AB  - OBJECTIVE: Bacterial vaginosis of pregnant woman is an important factor of
      appearance of the PROM in result of intrauterine infections on every stage of
      pregnancy. Frequency exist of intrauterine infection evaluate from 1 to 10%
      pregnancies. Clinical chorio-amnionitis complicates 1-5% of term pregnancies, but
      nearly 25% of preterm deliveries and really increase morbidity and mortality of
      newborns and they are also a reason of mothers morbidity. A condition of
      recognition the intrauterine infections is ascertainment of infection factor risk
      of mother and appearance of clinic symptoms of newborns. The aim of this work was
      a valuation of dependence between bacterial flora taken from cervics uteri of
      pregnant woman with PROM who gave birth with preterm below 32 weeks and a
      presence of clinic and laboratory symptoms of infections and the presence of
      bacterial flora in blood culture of the newborns. MATERIAL AND METHODS: 37
      pregnant women at the age from 20 to 43 hospitalized in Department Perinatology
      ICZMP between 1999-2001 because of PROM and a threat of preterm labor at the
      fetal age from 24 to 32 weeks were taken by an analysis. The average time of
      amniotic liquid outflowing before the labor was 11.1 days +/- 8.63, average
      length persistence of pregnancy was 27.6 hbd +/- 1.85, average born mass was 1029
      g +/- 187.5. Laboratory factors and clinics symptoms chorionamnionitis,
      bacteriology cultures of swabs from cervics uteri and information of the labor of
      pregnant women were analyzed. Diagnostics of newborns contained: making of blood
      cultures and skin, nose, throat, urine cultures, estimation WBC and level CRP,
      estimation of lungs X-ray. RESULTS: In result of bacteriology cultures from
      cervics uteri of mothers gained bacteria of frequent occurrence: Staphylococcus
      epiderm.--27%, E. coli--19%, Streptococcus gr. B--10.8%, Enterococcus foecalis-
      8.1%. In result of bacteriology cultures of newborns blood gained bacteria of
      frequent occurrence: Staphylococcus epiderm.--13.5%, Staphylococcus haemolitycus-
      10.8%, Klebsiella pneumoniae--10.8%, Pseudomonas aeruginosa--8.1%. In 97.3% cases
      at newborns appeared inborn infections in a shape of pneumonia confirmed by X
      ray. Confirmation of intrauterine infection in histopathology examination of the
      placenta in a shape of chorionamnionitis was shown in 25 cases, in other words in
      67.5%. Positive results of pathogenic bacteriology flora cultures taken from
      cervics uteri was in 50% pregnant woman, however in 43% of newborns bacteriology
      cultures of the blood were positive. In none of the analyzed preterm labor cases
      with PROM bacterial flora from positive cultures taken from cervics uteri of
      mothers did not correlate with bacterial flora found in blood cultures of
      newborns. CONCLUSIONS: On a base of analyzed values PROM of mothers with
      bacterial vaginosis is the important factor risk of the evolution of intrauterine
      infections of newborns, besides did not ascertain the dependence between the
      values of bacteriology cultures taken from cervics uteri of mothers and the
      values of bacteriology cultures of the newborns blood with clinic symptoms of
      intrauterine infection.

PMID- 14669429
TI  - [Urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion in women with pregnancy
      complicated with hypertension].
AB  - OBJECTIVES: Hypertensive disorders in pregnancy are one of the major mortality
      risk factors for mother and fetus. Although pathomechanisms of hypertension are
      extreme complex, the involvement of kidneys usually occurs. N-acetyl-beta-D
      glucosaminidase (NAG) is a lysosomal enzyme which is located in renal tubular
      cells. Therefore an elevation of urinary NAG activity serves as a marker of
      tubular cell damage. AIM: Evaluation of renal tubular damage in pregnant women
      with different types of hypertension by determination of urinary NAG activity.
      MATERIAL AND METHODS: The study comprised 84 pregnant women in third trimester,
      divided according to type of hypertension into 3 subgroups: pregnancy induced
      hypertension (n = 58), preeclampsia (n = 13) and chronic hypertension (n = 13).
      The control group comprised 36 healthy pregnant women. Urinary NAG activity was
      measured in the second morning urine samples by colorimetric method and the
      results were expressed as NAG/creatinine ratios (NAG/Cr). RESULTS: The highest
      NAG/Cr ratios were found in women with preeclampsia (median-1.520 U/mmol) and in
      women with pregnancy induced hypertension (median-0.874 U/mmol) and both results
      differed significantly from those in controls (median-0.782 U/mmol). There was
      slight positive correlation between NAG/Cr ratios and systolic blood pressure (r
      = 0.225, p < 0.05). CONCLUSIONS: Hypertension in pregnancy may lead to renal
      tubular damage, however clinical significance of this phenomenon requires further
      studies.

PMID- 14669430
TI  - [Diagnostic methods for fetal malformations in the first half of pregnancy].
AB  - INTRODUCTION: Fetal abnormalities are the most common cause of perinatal and
      postnatal death and infant handicap. For this reason prenatal screening (for
      fetal malformation) has become a routine part of obstetric care in many
      countries. Most often used are biochemical tests and continuously developing
      ultrasound diagnostics which makes possible precise analysis of the fetal
      morphology. There is interesting to establish a noninvasive test for the early
      detection of fetal malformation in pregnancy which is based on ultrasound
      examination (NT measurement from the 10th to the 19th weeks, presence of nasal
      bone in the first trimester ultrasound), correlated with serum concentration of
      AFP, beta-HCG and oestriol in the second trimester of pregnancy (triple test).
      The main aim of the study was to establish a diagnostic schema for detection of
      fetal malformations based on NT measurement in the first and second trimester
      coupled with triple test performed in the second trimester. MATERIALS AND
      METHODS: A group of 775 pregnant women from the 10-th week of pregnancy until
      childbirth has been put under examination. Between the 10th and the 14th and than
      between 15th and 19th week of pregnancy ultrasound examination with fetal
      biometry and NT measurement was done. NT measurements have been performed in
      accordance with the standards worked out by professor K. Nicolaides. At the first
      ultrasound examination the presence of the nasal bone was observed. The next step
      was performing the triple test between the 15th and 19th week of pregnancy. On
      the same day as second ultrasound examination blood was taken to determine the
      results of the triple test (ELISA method). The obtained results have undergone
      statistical analysis. RESULTS: The age of women qualified for the examination
      oscillated between 15 and 45 (over 35 -9.4%). There were 8 fetal malformations
      recognized all connected with the chromosomal anomalies, namely, 4 Downs
      syndrome, 2 fetuses with trisomy of the 18th pair of chromosomes and 2 with
      triploidy. At all physiologic pregnancies nasal bone was seen during first
      ultrasound examination. The obtained results of nuchal fold measurements and
      concentrations for the parameters of the triple test have been the basis to
      calculate medians in the particular weeks of pregnancy. In all the cases of
      genetic malformations the widening of the nuchal fold above 99 percentile (MoM
      NT) has been observed. Fetal nasal bone were absent in 62.5% first trimester
      ultrasound examinations. The risk of the occurrence of a genetic malformation
      resulting from the mother's age combined with the risk connected with the NT
      measurements and the results of the triple test for the cut-off point 1:250
      (which seems to be the best for this population) gave 100% sensitivity, 0.6% % of
      false positive results and the positive predictive value of 80%. The above
      mentioned results are better than the ones which were obtained within the triple
      test only, where for the previously fixed cut-off point 1:250 sensitivity reached
      63%, positive predictive value 25% and 4.4% false positive rate. Performing the
      so-called integrated test in which the risk of the occurrence of any malformation
      is estimated on the basis of the NT measurement in the first and the second term
      of pregnancy seems to be far more useful. CONCLUSIONS: Diagnostic schema for
      detection of fetal malformations in the first half of pregnancy which is based on
      ultrasound examination (NT measurement from the 10th to the 19th weeks),
      correlated with serum concentration of AFP, beta-HCG and oestriol in the second
      trimester of pregnancy (triple test) is very sensitive and safe method of the
      prenatal diagnosis leading to significant decrease of the invasive procedures
      (amniocentesis).

PMID- 14669431
TI  - [Usefulness of the examination of fetal blood oxygen saturation (FSpO2) and fetal
      heart rate (FHR) as a prognostic factor of the newborn outcome].
AB  - OBJECTIVES: Cardiotocography has become the standard for fetal monitoring in
      labor. False-positive findings during electronic fetal heart rate monitoring may
      were not associated with neonatal acidemia. Because of the poor specificity of
      fetal heart rate monitoring in predicting fetal distress, new methods are being
      investigated as a way to improve the accuracy of assessing the infant's condition
      during labor. DESIGN: The aim of this study was to determinate the efficiency of
      fetal blood oxygen saturation (FSpO2) and computer analysis of the fetal heart
      rate (Co-CTG) in the late 1-st stage of labor as a prognostic factor of newborn
      acidemia. MATERIALS AND METHODS: Total 62 subjects were studied. During labors
      and deliveries fetal oxygen saturation was continuously recorded, with use of
      Nellecor N-400 fetal pulse oximeter and continous CTG were performed by Hewlett
      Packard 50A. Transdermal fetal oxygen saturation measurements and CTG results
      obtained during the labors was analyzed using MONAKO system (ITAM Zabrze). The
      results were compared with the values of pH and base deficit in the umbilical
      artery measured just after delivery. RESULTS: The sensitivity, specificity,
      negative, positive predictive values and Youden factor based on FHR and FSpO2,
      for prognosis of neonatal acidosis were: 65%, 80%, 16%, 97.5% 60% and 0.135
      respectively FHR; and 100%, 60%, 100%, 96.8% and 0.968 respectively FSpO2.
      CONCLUSIONS: 1. The examination of fetal blood oxygen saturation in the labor is
      a useful prognostic factor of the newborn outcome. 2. The best predictive value
      for intrapartum fetal asphyxia with metabolic acidosis was found when fetal pulse
      oximetry is added to cardiotocography.

PMID- 14669432
TI  - [Evaluation of fetal right coronary artery blood flow velocimetry].
AB  - OBJECTIVES: In the present study fetal right coronary artery blood flow
      velocimetry was assessed. DESIGN: The prognostic value of the fetal right
      coronary artery blood flow velocimetry was evaluated in relationship with
      parameters of newborn's condition after birth. MATERIAL AND METHODS: The study
      was performed in 102 cases of pregnancies complicated by pregnancy induced
      hypertension. Blood flow velocimetry was visualized from fetal right coronary
      artery and correlated with perinatal outcome parameters. RESULTS: Fetal coronary
      blood flow velocimetry was visualized only in 11 cases. Coronary blood flow
      velocimetry visualisation correlated with each parameter of after-birth
      evaluation. The method has the highest specificity (97.7%) and positive
      prognostic value (85%) concerning evaluation of newborn's condition. CONCLUSIONS:
      Fetal right coronary artery blood flow velocimetry visualisation is a late sign
      of chronic fetal hypoxia. This seems to be a factor which causes maximal coronary
      vessels dilatation and allows oxygenation of fetal heart muscle.

PMID- 14669433
TI  - [Evaluation of fetal heart anatomy at the end of the first trimester and the
      beginning of the mid-trimester].
AB  - OBJECTIVE: To evaluate fetal heart anatomy in the late first and in the early
      second trimester. MATERIALS AND METHODS: The study included 75 fetuses between 11
      and 19 weeks' gestation. Exams were performed using transabdominal or
      transvaginal probes. RESULTS: The proportion of cases successfully visualized to
      all cases in particular week of pregnancy was following: 11 week--0/1 (0%), 12-
      1/1 (100%), 13 week--1/1 (100%), 14--18/23 (79%), 15--6/9 (67%), 16--23/27 (86%),
      17--4/5 (80%), 18--6/6 (100%), 19--2/2 (100%). In 11 weeks' gestation two
      ventricles and two atrias could be imaged. Anatomy was seen from 12 weeks'
      gestation with transvaginal and from 13 weeks' gestation with transabdominal
      transducers. Two tricuspid regurgitations were detected. The interventricular
      septum was the most difficult structure to visualize in all cases. The grey scale
      alone was not sufficient for accurate examination of the heart and it was
      necessary to use colour Doppler to confirm normal forward flow to both ventricles
      and to identify outflow tracts. CONCLUSIONS: 1. Successful visualization of the
      heart in early pregnancy is possible from 12 weeks' gestation with transvaginal
      and from 13 weeks' gestation with transabdominal probe. 2. Fetal echocardiography
      between first and second trimester should lead to better understanding of fetal
      hemodynamics in normal and abnormal fetuses and help to introduce new therapeutic
      treatment in some cases.

PMID- 14669434
TI  - [Triplet pregnancy complicated by intrauterine death of two fetuses--case
      report].
AB  - INTRODUCTION: Multiple pregnancy still constitutes a difficult therapeutic
      problem in perinatology. The incidence of this phenomenon describes Hellin's
      formula: the number of twin pregnancy is 1/n, triplet--1/n 2 etc. Among
      complications observed in multiple pregnancy intrauterine death of one or more
      foetuses is not rare. Due to progressive disturbances in haemostasis the risk for
      a mother and remaining live foetus increases with gestation. The aim of this
      paper was to present a case report of triplet pregnancy complicated by an
      intrauterine death of two foetuses. REPORT: 33 years old patient was diagnosed by
      ultrasound in the 19th week of her second gestation (1 child) a triplet
      pregnancy. Three live foetuses were seen then with biometry of about 14/15
      gestational week There was one joint placenta on the back uterine wall and two
      children were sharing an amniotic sac. On the consecutive ultrasound examination
      the three foetuses were alive, but only one had a biometry for 21st week, two-
      were slowing down having measurements adequate for 19/20th week. After four weeks
      on usg the death of two siblings was confirmed (age 19/20 gestational week). One
      remaining live foetus was according to usg 24 weeks old. The patient was
      transferred to the II Dept. Even though no disturbances in coagulation were
      observed, low molecule heparin prophylaxis was introduced. During hospital stay a
      gestational diabetes was diagnosed well corrected by diet only. Coagulation
      parameters as well as infection indexes were regularly monitored. The foetal well
      being was established by non-stress test, biophysical profile and Doppler
      vascular flows. After 39 days of hospitalisation an elevation of fibrin
      degradation products (FDP) was noted so the dosage of low molecule heparin was
      immediately increased to the therapeutic values. In spite of that FDP still were
      growing. It was decided to introduce a steroids treatment to accelerate the
      maturity of foetal lungs. In the 31st week according to usg, after PROM, the
      emergency caesarean section was performed. Daughter, breech presentation,
      weighting 1380 grams was born, with Apgar score 6-8-8. At the beginning
      artificial ventilation was necessary. After 11 days thanks to gradual improvement
      transfer from NICU to prematurity ward was possible. The postoperative period was
      uneventful and a mother was discharged home on the 7th day. CONCLUSION: Careful
      monitoring of a survived foetus as well as coagulation system has allowed to
      extend the duration of pregnancy for further 45 days and to deliver an infant
      capable to live.

PMID- 14669435
TI  - [Four main reasons of maternal death in Poland between 1991-2000].
AB  - Maternal death during pregnancy, labour and puerperium constitutes the main
      problem of prenatal medicine and still a major public health topic. In this work
      we analyses maternal deaths in Poland between 1991-2000. There were 4,404,641
      live births and 462 maternal deaths. Among them there were 402 direct ("true")
      maternal deaths with mortality rate 9.1 per 100,000 live births and 60 indirect
      maternal deaths (rate 1.4). There were 218 cases of pregnancy associated deaths
      (rate 4.9). The main causes of direct maternal deaths were as follows:
      haemorrhage--33.6% (rate 3.1), sepsis--27.3% (rate 2.5), amniotic fluid embolism-
      22.4% (rate 2.0) and pregnancy induced hypertension 16.7% (rate 1.5). Increasing
      maternal age is one of important risk factor for mortality. Over 30% of direct
      pregnancy related deaths were noted within women above 35 years. Unsatisfactory
      antenatal care, management deficiency and patient's neglect were main risk factor
      foe fatal outcome. Practical conclusions should be issued as general rules,
      instructions and recommendations. Between one third to one half of the maternal
      deaths are considered to have been preventable.

PMID- 14669436
TI  - [Complications in women with pre-gestational diabetes and glycemic control
      estimated by general glycemic control index (GCI)].
AB  - Pre-gestational diabetes is a serious risk factor in pregnancy and delivery.
      Complications during pregnancy in this group of women depend on the glycemic
      control and on the clinical course of diabetes. MATERIAL AND METHOD: On the
      period of 1991-2001, 186 pregnant women with diabetes diagnosed before pregnancy
      were hospitalized in Ob/Gyn Department, Medical University of Bydgoszcz. In this
      study, 178 deliveries and 8 abortions were analyzed. The selected glycemic
      control indices-GCI (General Control Index) were analyzed in diabetic women with
      non-complicated pregnancies and in women with complications during pregnancy.
      RESULTS: The most frequent complications during pregnancy were premature delivery
      (32%) and hypertension (13%). Deliveries before the end of 37 week of pregnancy
      were more frequent in women with more complicated diabetes. Glycemic control in
      diabetic mothers who delivered prematurely was worse then in women with normal
      outcome. An increased rate of congenital malformations (6.7%) in the newborns
      were noted in women with very poor glycemic control in the first months of
      pregnancy. Perinatal mortality was higher than that of the non-diabetic
      population, and was at the level of 3.4%. CONCLUSIONS: 1. Glycemic control in
      women with diabetes diagnosed before pregnancy who delivered prematurely, was
      worse then in women who delivered at the term. 2. High rate of the congenital
      malformations (6.7%) in the newborns was observed in patients with very poor
      glycemic control in the first months of pregnancy.

PMID- 14669437
TI  - [Lamellar body count and interleukin-6 levels in women with preterm labor].
AB  - Our purpose was to investigate the amniotic fluid lamellar body count and
      interleukin-6 levels in women with preterm labor. The study was carried out on 50
      amniotic fluid collections obtained by amniocentesis or during cesarean delivery.
      Concentration of lamellar body (CL) and interleukin-6 (IL-6) were performed. We
      found significantly lower lamellar body count values in women at risk of preterm
      delivery before 34 weeks' gestation and elevated amniotic fluid IL-6
      concentration (CL--20.81 +/- 6.73 x 103/ul, IL-6--318.3 +/- 18.7 pg/ml) when
      compared with pregnancies at term (CL--77.1 +/- 28 x 103/ul, IL-6--142 +/- 15.3
      pg/ml).

PMID- 14669438
TI  - [Evaluation of serum sICAM-1 and sVCAM-1 concentration in patient at risk of
      preterm delivery].
AB  - Aim of the study was to assess the serum adhesion molecules concentration in
      patients at risk of preterm labour. Sixty-three patients were divided into two
      groups basing on cervical evaluation (Bishop's score > or = 6 and < 6). The
      assessment of sICAM-1 and sVCAM-1 levels in serum were carried out by
      immunoenzymatic ELISA test utilizing monoclonal antibodies (moAb) against human
      sICAM-1 and sVCAM-1 (ELISA system, R&Q, USA). Among the patients at risk of
      preterm labour and Bishop's score > or = 6 statistically higher serum levels of
      sICAM-1 were found. There were no statistically significant differences in sVCAM
      1 levels between examined groups. We conclude that serum sICAM-1 determination
      might improve the prediction of preterm birth.

PMID- 14669439
TI  - [Concentration of thrombin activatable fibrinolysis inhibitor (TAFI) in cord
      blood and maternal blood during labor].
AB  - The concentration of TAFI in cord blood plasma has not been studied yet. We have
      measured its activity in plasma both in cord blood and mother's blood during
      labour. The study group consisted of 26 parturient women, 18 primiparas and 9
      multiparas with normal course of pregnancy and delivery. Activity of TAFI was
      evaluated by chromogenic method (Actichrome Plasma TAFI Activity Kit). The level
      of TAFI in cord blood plasma was 4.20, range 3.80-6.40 micrograms/ml and in
      mother's blood 10.50, range 7.60-13.50 micrograms/ml, thus it was significantly
      lower (p < 0.0001). CONCLUSION: TAFI is present in the cord blood plasma but its
      concentration is about 50% of that in the mother's blood.

PMID- 14669440
TI  - [Serum concentration of soluble vascular-cellular adhesion molecule-1 (VCAM-1)
      and expression of its receptor VLA-4 on the surface of peripheral blood and
      decidual lymphocytes of preeclamptic women].
AB  - INTRODUCTION: Vascular-cellular adhesion molecule-1 (VCAM-1) overexpression on
      the cells' surface is stimulated by pro-inflammatory cytokines, bacterial
      endotoxins, reactive oxygen species and lipid peroxides. In the serum also the
      soluble form of VCAM-1 (sVCAM-1) is present. The beta 1-integrin family molecule
      VLA-4 (CD49d) is natural ligand for VCAM-1. Increased concentrations of sVCAM-1
      as well as overexpression of VLA-4 were observed during inflammatory reaction.
      THE AIM: To study sVCAM-1 serum concentrations and CD49d+ subpopulations of
      peripheral blood and decidual lymphocytes of the 3rd trimester healthy and
      preeclamptic women. MATERIALS AND METHODS: The study groups: n = 21 healthy
      pregnant women, n = 33 preeclamptic women (preeclampsia defined as blood pressure
      > 140/90 mmHg with proteinuria > 0.3 g/24 h). Clinical states of known
      pathogenesis which could possibly interfere with values of studied parameters
      were excluded. Exclusion criteria were also uterine contractions and premature
      rupture of amniotic membranes. Decidua was collected exclusively during elective
      caesarean sections. The sVCAM-1 concentration (ng/ml) was estimated using ELISA
      procedure, while percentage (%) of CD49d+ lymphocytes in the whole blood and
      homogenized decidual tissue, using flow cytometry. The results were presented as
      median value with 25% and 75% cut off values. Statistical analysis was performed
      with U-Mann-Whitney test (p < 0.05). RESULTS: Preeclamptic women presented with
      increased sVCAM-1 serum concentrations (532.5 (400.0/605.0) ng/ml vs. 387.0
      (320.0/416.5) ng/ml, p < 0.0005), increased (%) of CD49d+ peripheral blood (92.0
      (88.0/96.0)% vs. 52.9 (47.5/55.8)%, p < 0.0000001) and CD49d+ decidual
      lymphocytes (88.0 (84.0/90.0)% vs. 80.5 (74.0/85.6)%, p < 0.05). CONCLUSION:
      Described change suggest that immunological mechanisms similar to inflammatory
      reaction could be involved in pathogenesis of preeclampsia in peripheral blood as
      well as locally inside maternal-fetal interface.

PMID- 14669441
TI  - [Maternal serum and amniotic fluid IL-1 alpha, IL-1 beta, IL-6 and IL-8 levels in
      preterm and term labor complicated by PROM].
AB  - Cytokines may be implicated in the pathophysiologic mechanisms of preterm and
      term labor. Many studies indicate cytokines as predictors of preterm delivery and
      explain partially mechanism of preterm uterine contractions. Complicated
      relations between mediators in systemic fluids of a fetomaternal unit require
      further explorations. The right diagnosis and management require better
      understanding of these relationships. OBJECTIVES: The comparison of IL-1 alpha,
      IL-1 beta, IL-6 and IL-8 levels in maternal serum and amniotic fluid in term and
      preterm labor complicated by PROM. MATERIAL AND METHODS: In 44 patients in
      premature labor with PROM (group I) and 33 patients in labor at term with PROM
      (group II) cytokines levels were estimated one time in amniotic fluid: just after
      PROM, and two times in maternal serum: just after PROM and during labor. RESULTS:
      Amniotic fluid cytokines levels were significantly higher in group I than in
      group II. Maternal serum cytokines concentrations of IL-1 alpha and IL-1 beta in
      group I were significantly higher than in group II. IL-6 level was significantly
      higher in group II than in group I. In both groups maternal serum IL-6 levels
      during labor significantly increased in comparison to IL-6 levels just after
      PROM. No correlations between amniotic fluid and maternal serum cytokine levels
      at PROM were observed. CONCLUSIONS: Higher amniotic fluid cytokines levels in
      patients with preterm labor complicated by PROM than in labor at term with PROM
      indicate possible differences between PROM mechanisms in preterm and term labor.
      The increase of IL-6 level during labor can be related with the possible role of
      this cytokine in the immunological mechanism of the labor beginning. No
      relationships between amniotic fluid and maternal serum levels of investigated
      cytokines in PROM suggest the presence of the barrier stopped cytokines transfer
      by the placenta and the complete separation of these two compartments.

PMID- 14669442
TI  - [Prenatal and postnatal cardiologic evaluation of normal twin from acardiac twin
      pregnancy--case report].
AB  - The aim of the paper was to describe dynamic changes in 'pump twin's' circulatory
      system within clinical observation, indication analysis for premature delivery
      due to cardiovascular findings and long-term postnatal follow up. In
      echocardiographic examination of 'pump twin' no structural heart defects but
      functional changes in cardiovascular system have been detected (cardiomegaly,
      right heart disproportion, tricuspid valve regurgitation). Within 10-week
      observation polyhydramnios did not increased significantly, no amnioreduction
      procedures had been performed. Due to single umbilical artery in 'pump twin' a
      cytogenetic examination had been performed revealing a normal karyotype. When the
      first signs of abnormal Doppler flows appeared such as increased PI of umbilical
      artery and DV and cardiomegaly with TR--caesarean section was performed at 33
      weeks of gestation. Echocardiography performed in the first day of life findings:
      right atrium and ventricle enlargement, significant tricuspid valve regurgitation
      (V max 3 m/s), a prenatally undetected, small perimembrane-part ventricular
      septal defect. At the age of 6-months a non-significant VSD with tricuspid valve
      septal leaflet closure and ASD II has been confirmed. The infant is
      systematically followed-up by paediatricians, cardiologists and neurologists and
      her further neurodevelopment appears to be slightly retarded.

PMID- 14669443
TI  - [Analysis of mode of delivery in cases with fetal premature atrial contractions].
AB  - OBJECTIVE: Premature atrial contractions are common in obstetrical practise but
      there is little information available on recommended management and mode of
      delivery. DESIGN: The aim of the study was to describe our clinical experience in
      the management of fetal arrhythmia including the indications for certain time and
      way of labour. MATERIALS AND METHODS: 128 fetuses with diagnosed supraventricular
      arrhythmia described as atrial extrasystole were examined. They were divided into
      3 main groups: group I (84 fetuses) with single PAC, group II (37 fetuses) with
      quantitatively significant arrhythmia or accompanied by another kind of
      arrhythmia and group III (7 fetuses) associated with extracardiac abnormalities.
      RESULTS: Among 128 fetuses with supraventricular arrhythmia, 44 cases (31%)
      required systematic monitoring. Quantitatively significant arrhythmia was
      recognized in 15 cases, blocked bigeminy (2:1) in 2 fetuses, 10 cases were
      accompanied by another arrhythmias: 4x SVT, 4x sinus bradycardia, 2x premature
      ventricular contractions (PVC). There were 3 fetuses diagnosed with heart defects
      and 7 with extracardiac malformations. Fetal echocardiography revealed additional
      functional circulatory changes in 7 fetuses with premature atrial contractions.
      Myocarditis was recognized in 2 fetuses. The mode of delivery was analyzed in 128
      cases. In the first group 27 patients (32%) underwent caesarean section, in the
      second group--23 (62%), in the third group 3 patients (43%), respectively.
      Cardiac indications for caesarean section equalled 22% of all the indications
      occurring in fetuses suffering from arrhythmia. CONCLUSIONS: Caesarean section is
      much more commonly performed among fetuses diagnosed with arrhythmia accompanied
      by another fetal anomalies comparing to the group of fetuses with isolated
      arrhythmia. Although there are no particular cardiac indications for such way of
      delivery, total amount of caesarean sections performed in that group is really
      great. Above all, it may suggest that the obstetrician is under pressure of
      stress while making decision concerning caesarean section performance, even when
      there are no other indications and the condition of fetus is stable enough.

PMID- 14669444
TI  - [Newborn's postnatal maturity index as the health marker of the mother].
AB  - OBJECTIVES: Newborns of both high and low body weight, as well as of higher or
      lower gestational age and length are born within the wide range of the six weeks
      of the biological norm. The correlation between the fetal mass and height is
      high, however the correlation of those two basic features with the fetal maturity
      is half as high. In view of the above, in order to verify the proper time of
      pregnancy ending, particularly if it is an instrumental one, it is necessary to
      assess the newborn's maturity index, which is also an indicator of the mother's
      health. Consequently, the index has a prognostic value for assessment of both the
      mother's and the infant's morbidity. MATERIALS END METHODS: Human maturation
      process was evaluated by means of at least two ultrasonographic measurements of
      fetal parameters < or = 28th week to determine an individual birth term in 2500
      cases, construed as the day when the fetus reaches full maturity to self
      dependent life and the mother becomes ready for the labor. Regardless of the
      method of assessment, the most important criterion of the sufficient pregnancy
      duration is the degree of the fetal maturity assessed immediately after the
      labor, i.e. Klimek's score (K) during the routine neonatal evaluation accompanied
      by the assessment of the newborn infant's adaptive efficiency expressed in the
      popular Apgar score (A). RESULTS AND CONCLUSIONS: It was found that the point
      count in K score is a more sensitive index of the newborn infant's wellbeing than
      the A score. Fetal development in the mother's womb progresses according to the
      auxological laws, to which the K score point-count conforms, unlike the A score.
      This study summarizes the latest studies on this subject in infants born both
      from physiological and pathological labors.

PMID- 14669445
TI  - [Pregnancy in a patient with Turner syndrome].
AB  - Fertility in patients with a diagnosis of Turner's syndrome confirmed by
      karyotype examination is a very rare phenomenon. Only in 2% of all cases the
      pregnancy is a result of a spontaneous ovulation and intrauterine fertilization.
      Due to high proportion of complications occurring in pregnancy, in labour and in
      puerperium, only minority of patients can expect delivering a healthy infant.
      Literature data indicate that 40% of patients with Turner's syndrome give birth
      to a healthy child. Other pregnancies are terminated either by delivering a child
      with congenital defect or by a spontaneous abortion. We report a case of a 26
      year-old patient with Turner's syndrome (46XX/45XO) who menstruated regularly
      after hormonal replacement therapy. She had regular menstrual bleeding through
      period of two years, after withdrawal of hormones administration. In march
      diagnosis of pregnancy was made, as a result of a spontaneous ovulation. The
      healthy, full-term fetus was born in 40th week of pregnancy.

PMID- 14669446
TI  - [Evaluation of endometrial biopsy in postmenopausal women before HRT].
AB  - One of the reasons for not commencing or withdrawal of HRT in women is their fear
      for breast and endometrial cancers. Does ultrasonographic valuation guarantee
      sufficiently patient's safety? Most investigators do not recommend further
      endometrial diagnostics with endometrial thickness less than 4 mm. Endometrial
      biopsy is advised in cases of irregular uterine bleedings with normal endometrial
      image or when any endometrial pathology is suspected. In Poland the most
      frequently performed procedure of endometrial diagnostics is D&C. Our proposition
      was to offer endometrial biopsies to all patients who were taken HRT for more
      than 5 years or, despite having strong climacteric ailments, refused to take it
      because of their cancerophobia. AIM OF STUDY: To evaluate the usefulness of
      aspiration endometrial biopsy in women after menopause qualified for HRT.
      MATERIAL AND METHODS: In 84 females, being postmenopausal (amenorrhoeic for at
      least 12 months) and qualified for HRT, aspiration endometrial biopsies were
      performed in outpatient clinics. Age of women ranged 46-63 years, mean 57.3.
      Attained results were compared to ultrasonographic endometrial evaluation. Such
      factors as patient's age, menopausal age (years from last menstrual period) and
      previous administration of HRT were taken into our account (maintaining a 3-month
      wash-out interval). In 74% of women we have got a material being sufficient for
      histological evaluation. Form clinical point of view the most important for us
      was to exclude a proliferative or neoplastic process within endometrium. One of
      endometrial polyps was omitted in USG study, we were surprised also while
      detecting endometrial carcinoma cells in endometrium below 3.5 mm. In one
      postoperative slide the cells of endometrial ovarian carcinoma (with infiltrated
      Fallopian tube) were detected. CONCLUSION: Endometrial biopsy seems to be a
      useful, effective and cheap method of endometrial diagnostics also in women after
      menopause.

PMID- 14669447
TI  - [Estimation of telomerase transcriptive activity in the umbilical cord and the
      mother's venous blood cells].
AB  - Stem cells possess the ability of the partition and differentiation into other
      cells, practically lifelong of the organism. The potential of the self-extraction
      of these cells practically unrestricted and results probably from the telomerase
      gene activity, especially subunit hTERT. To the analysis of 11 samples of the
      umbilical cord and mothers blood received immediately after the childbirth in
      which one compared the expression of telomerase genes hTERT, TP1, hTR. Four cases
      ascertained the expression subunit hTERT in the umbilical cord blood at the lack
      its transcripts in the venous blood of mothers. In one case we found 10-times
      higher concentration of subunit hTERT in the umbilical cord blood than in the
      venous blood of the mother. 6 cases did not demonstrate the expression of the
      hTERT nor in the umbilical cord blood nor in the venous blood of mothers. The
      transcriptive activity TP1 and hTR did not show differences among investigated
      groups. Received results put the question or the transcriptive activity subunit
      hTERT in the umbilical cord blood is a results of the presence of stem cells.

PMID- 14669448
TI  - [Effect of combined surgical and pharmacologic treatment on peripheral blood
      cytokine concentrations in women with endometriosis].
AB  - Endometriosis is a disease causing the growth of endometrial tissue outside its
      proper localisation. The frequency of this disease occurrence is estimated for
      about 10% of women at reproductive age. More and more often scientific studies
      reveal the key role of immunological disorders as the factor contributing to the
      development of endometriosis. Investigators pay their attention not only on the
      composition of immunological cells, but on the amount and proportion of their
      products, including cytokines, as well. Aim of the study was the evaluation of
      cytokine generation by peripheral blood lymphocytes derived from women with
      endometriosis, as well as the estimation of combined surgical and pharmacological
      treatment influence on this production. MATERIAL AND METHODS: The study group
      consisted of 72 patients treated in Surgical Gynecology Department of Polish
      Mother Health Centre Research Institute in Lodz, in years 1998-2002.
      Endometriosis was diagnosed during laparoscopy or laparotomy in 60 of them. The
      diagnosis was confirmed in histopathological examination. 14 of those patients
      were qualified to 6 months long Zoladex therapy (AstraZeneca), following the
      operation. Zoladex was used in a dose of 3.6 mg per month. Evaluation of the
      cytokine generation was performed before the treatment and repeated after the
      full therapy. 12 women with no signs of endometriosis lesions existence were the
      comparison group. Immunofluorescence method ELISA and ENDOGEN commercial kits
      were used for evaluating the cytokine concentration levels. RESULTS: Significant
      decrease in IFN-gamma generation (p < 0.05) by peripheral blood lymphocytes was
      noted in women with endometriosis before the treatment as compared to women
      without this disease. Therapy caused its increase and the difference was
      statistically significant. Significantly higher levels of the IL-4 generation
      after PHA stimulation were also observed in women with endometriosis then in
      women from the comparative group. The therapy of endometriosis caused the
      decrease in IL-4 production, but the differences were not statistically
      significant (p < 0.05). Significant differences in IL-4 generation after the
      treatment as compared to the values noted before the treatment were observed only
      after using conkanavaline A as the lymphocyte stimulator. Generation levels of IL
      2, IL-10 and IL-12 did not vary significantly after the combined surgical and
      pharmacological treatment of endometriosis. CONCLUSIONS: 1. Significant decrease
      in IFN-gamma concentration was shown in patients with endometriosis, which proves
      the role of this cytokine in the pathogenesis of this disease. 2. Combined
      surgical and pharmacological treatment causes the increase in IFN-gamma
      production by peripheral blood lymphocytes.

PMID- 14669449
TI  - [Tissue-type plasminogen activator (T-PA) and plasminogen activator inhibitor
      (PAI-1) in human follicular fluid during gonadotropin-induced ovulation].
AB  - OBJECTIVES: Plasminogen activators and their inhibitors have been implicated in
      the process of fibrinolysis, tissue remodeling, and ovulation. To evaluate the
      role of t-PA and PAI-1 in human ovulation, we obtained follicular fluid (FF) from
      preovulatory follicles of patients undergoing IVF-ET. Concentrations tPA and PAI
      1 were analyzed in relation to oocyte maturation. Levels of tPA and PAI-1
      obtained after COH were compared to the tPA and PAI-1 concentrations in the
      follicular fluid of healthy, fertile women. MATERIALS AND METHODS: FF was
      collected from 66 infertile patients undergoing ovulation induction using either
      short or long protocol. FF was obtained 36 hours after hCG (Pregnyl)
      administration. The control group consisted of 16 fertile women with unstimulated
      cycles. Concentrations of t-PA Ag and PAI-1 Ag were measured using Elisa kits
      (Bioopol). RESULTS: The average follicular fluid tPA concentration of patients
      undergoing IVF-ET treatment was significantly lower (0.039 vs 0.117 ng/mg
      protein; p < 0.0005), whereas PAI-1 significantly higher (3.261 vs 0.135 ng/mg; p
      < 0.0001) compared to the control group. Concentrations of tissue-type
      plasminogen activator in FF of patients with 5 or more mature oocyte were
      significantly lower (0.017 vs 0.056 ng/mg) and levels of PAI-1 higher (3.49 vs
      2.9 ng/mg) in comparison to cases involving < 5 oocytes. CONCLUSIONS: 1.
      Concentration of tPA in the follicular fluid is significantly lower whereas PAI-1
      level significantly higher in patients undergoing COH. 2. Follicular fluid tPA
      and PAI-1 concentrations may be a crucial factors reflecting oocyte maturity.

PMID- 14669450
TI  - [Effect of homocysteine concentration in follicular fluid on a degree of oocyte
      maturity].
AB  - Homocysteine (HCY) is an amino acid being a methionin catabolite. The action of
      HCY is multi-directional and not yet fully known. Follicular fluid also contains
      homocysteine. Disorders of the composition of follicular fluid as an
      microenvironment of an oocyte may influence its development. AIM: The aim of our
      study was to evaluate correlation between follicular fluid homocysteine
      concentration and degree of maturity of egg cell. MATERIALS AND METHODS: The
      research concerned 40 patients qualified for IVF-ET. Ovulation was stimulated
      according to the long protocol. 20 of 40 patients underwent folic acid
      supplementation. Pituitary suppression was performed by administration of the
      nafarelin. The subsequent follicular development was stimulated by HMG. To all
      patients 10,000 IU of hCG was administered 34-36 hours before follicle puncture.
      The oocytes obtained were assessed in respect of a degree of Veeck scale. In all
      patients, fluid samples were recovered from more than one follicle, centrifugated
      and frozen before analysis. Both in the follicular fluid and serum, homocysteine
      concentration was determined with the FPIA method. Concentration of the folic was
      measured with the MEIA method. RESULTS: These data support that homocysteine
      concentration in follicular fluid and serum was significantly lower in group with
      folic supplementation. The purpose of the research was to determine the
      dependencies between the concentration of HCY in follicular fluid and the quality
      of oocytes. It has been shown that in a group of women with folic supplementation
      and lower HCY concentration the percentage of oocytes in first and second degree
      of maturity was higher. CONCLUSIONS: 1. Supplementation of folic acid diminish a
      concentration of homocysteine in both--follicular fluid and serum. 2. Oocytes
      exposed to low homocysteine concentration present better quality and higher
      degree of maturity. 3. There is a correlation between follicular fluid
      homocysteine concentration and oocyte maturity.

PMID- 14669451
TI  - [Assessment of serum lipid peroxide levels and antioxidant status in females who
      had undergone total abdominal hysterectomy without closing of the peritoneum].
AB  - INTRODUCTION: Reactive oxygen species (ROS) generated after the trauma caused by
      surgical intervention, have the capacity to react in an indiscriminate manner
      leading to damage to almost any cellular component (proteins, nucleid acids) and
      to lipid peroxidation. The assessment of ROS generation intensity process may
      help in understanding of molecular processes observed in the intracellular
      environment after operations. The evaluation of antioxidative level may give an
      answer about the efficiency of antioxidative defence mechanism. The peritoneum is
      an organ of high metabolic activity, connected with ROS generation and
      participated in healing process. The modern opinions suggest closing of
      postoperative wound without closing of peritoneum. The aim of this study was
      assessment of antioxidant status and serum lipid peroxide levels in early
      postoperative period, in females who had undergone total abdominal hysterectomy
      without closing of peritoneum. MATERIALS AND METHODS: 30 women after total
      abdominal hysterectomy with salpingooophorectomy were studied, including 13
      patients after peritoneal suturing (control group--C) and 17 women with nonclosed
      peritoneum (study group--S). The total serum antioxidant status (FRAP) was
      evaluated spectrophotometrically. The concentration of lipid peroxidation
      products was assessed in serum collected before operation and 8 and 24 hours
      after, as the concentration of lipid hydroxyperoxides (HPETE), malonyl dialdehyde
      (MDA) and 4-hydroxyalkenals (4-HDA). RESULTS: The antioxidative level before
      operation was 1147.09 +/- 93.6 microM/l in S group; 1022.04 +/- 115.4 microM/l in
      C group and did not changed significantly in early postoperative period. MDA + 4
      HDA level before operation was 1.08 +/- 0.2 microM/l in S group and 1.06 +/- 0.2
      microM/l in C group; HPETE level before operation was 4.58 +/- 0.1 microM/l in S
      group and 4.72 +/- 0.1 microM/l in C group, 8 and 24 hours after the operation
      MDA + 4-HDA level increased respectively to 1.34 +/- 0.2 microM/l (by 27%; p >
      0.05) and 1.46 +/- 0.2 microM/l (37%) in S group and to 1.16 +/- 0.2 microM/l (by
      8%) and 1.62 +/- 0.2 microM/l (by 52%; p < 0.05) in C group. HPETE level
      decreased to 4.56 +/- 0.1 microM/l (by 1%) and increased to 5.23 +/- 0.2 microM/l
      (by 14%) in S group and increased respectively to 6.0 +/- 0.2 microM/l (by 27%; p
      < 0.01) and to 6.43 +/- 0.2 microM/l (by 36%; p < 0.01) in C group. CONCLUSIONS:
      The concentration of lipid peroxidation products after the operation was lower in
      study group, where peritoneum was left without closing. Total antioxidative level
      was the same in both groups. Obtained results suggest smaller ROS generation in
      study group.

PMID- 14669452
TI  - Incorporation of 14C-palmitic acid into phospholipids in the isolated rat uterus.
      Effect of exogenous ovarian steroids and gonadotrophin-induced ovulation.
AB  - Effect of different hormonal stage on incorporation of (1-14C)palmitic acid (PA)
      into the uterine phospholipids (PL) has been studied. Virgin female Wistar rats
      were divided into the following groups: ovariectomized 7 and 28 days, untreated;
      ovariectomized received a single injection of estradiol, ovarietomized received a
      single injection of progesterone (after estradiol-priming), intact cycling
      females received pregnant mares serum gonadotrophin, intact cycling females
      injected human chorionic gonadotrophin after PMSG-priming. Uteri horns were
      incubated a buffer containing 14C-PA. Lipids were extracted and fractionated
      using thin-layer chromatography. Estradiol increased PL-content, incorporation of
      (1-14C)-PA into the PL, while progesterone inhibited E-dependent effect,
      Gonadotrophin-induced ovulation provoked increase in uterine PL-content and
      remained a stimulatory signal for incorporation of (1-14C)-PA.

PMID- 14669453
TI  - [Effect of 17 beta-estradiol and phytoestrogen daidzein on the proliferation of
      pubocervical fascia and skin fibroblasts derived from women suffering from stress
      urinary incontinence].
AB  - OBJECTIVES: The past decade has witnessed many publications indicating that
      estrogens play an important role in the function of the female lower urinary
      tract. Sex steroids receptors have been discovered in areas of the brain involved
      in the initiation and control of micturition, as well as other target tissues:
      bladder, urethra and pubocervical fascia. Connective tissue metabolism and
      collagen biosynthesis are modulated by ovarian steroids. Estrogen deficiency has
      been linked to the reduction of total vaginal and periurethral collagen content.
      Therefore, menopause and hypoestrogenism have been associated with several
      urogenital complaints including stress urinary incontinence (SUI), urgency,
      recurrent infection and genitourinary prolapse. DESIGN: The main purpose was to
      evaluate the proliferation ability of fibroblasts from pubocervical fascia after
      exposure to 17 beta-estradiol and phytoestrogen daidzein. MATERIALS AND METHODS:
      Specimens of human pubocervical fascia were obtained from 8 perimenopausal women
      during IVS procedure. Fibroblasts were isolated and cultured by outgrowth
      technique. After reaching confluency fibroblasts were subcultured every four days
      and cells after passage number 3 to 8 were used for assessment. Next day culture
      medium was changed and cells were exposed to serial dilutions of 17 beta
      estradiol and daidzein in medium supplemented with only Serum Replacement 2. Cell
      proliferation was assessed after 96 hrs by means of MTT method. A human skin
      fibroblast culture served as a control. RESULTS: Pubocervical fascia fibroblasts
      showed increased proliferation capacity after 17 beta-estradiol than daidzein
      treatment. Proliferative activity of skin fibroblast was lower when compared to
      genitourinary cells in all groups investigated. CONCLUSIONS: The results indicate
      that, at least in vitro, fibroblasts from pubocervical fascia taken from women
      suffering from SUI are more capable to proliferate after estrogen treatment, when
      compared to skin fibroblasts. This is an indirect rationale for local estrogen
      treatment in case of female SUI.

PMID- 14669454
TI  - [Manifestation of glutathione S-transferase GSTM1 and GSTT1 in female patients
      with bleomycin-positive chromosome instability].
AB  - OBJECTIVES: The purpose of this research is to assess the incidence of gene
      polymorphisms coding the GSTM1 and GSTT1 enzymes in a population of female
      patients with chromosome instability. MATERIALS AND METHODS: The PCR method was
      used to determine the genotype for GSTM1 and GSTT1. The breaks per cell and the
      percentage of damaged cells were calculated. The separation point used to
      diagnose chromosome instability in tested females was assumed to be 2.5. RESULTS:
      In a tested population of 85 females with chromosome instability, the deletion of
      both the alleles of the GSTT1 gene was observed in 22 females (25% of the group)
      and deletion of both the alleles of the GSTM1 gene was observed in 42 females
      (53% of the group). In addition, the incidence of individual genes was calculated
      for the tested population. The X2 test showed that the differences between the
      observed and expected values of the tested genes were statistically immaterial,
      i.e. the likelihood of randomness for these differences exceeded 99%.
      CONCLUSIONS: No relationship between the manifestation of genotypes for the GSTM1
      and GSTT1 glutathione S-transferases and an increased chromosome instability
      confirmed with the bleomycin test was proven for a population of females with a
      neoplastic risk.

PMID- 14669455
TI  - [TVT tape usage in the treatment of stress urinary incontinence].
AB  - Stress urinary incontinence is one of the most common gynecological complains.
      The frequency of its occurrence is from 12 to 25 and even 60%. It is most often
      observed in patients after menopause, but in a few percent is also found in
      twenty and thirty years old women. During several years of searching the
      effective methods of stress urinary incontinence treatment, many operative
      techniques have been worked out, but none of them became a perfect one. The
      operation with the use of TVT tape is one of the newest methods of the stress
      urinary incontinence treatment. The aim of our study was the attempt of the
      estimation the TVT operation effectiveness in the treatment of stress urinary
      incontinence in women treated in Surgical Gynecology Department of Polish Mother
      Health Centre Research Institute in years 2000-2002. Performed analysis of 60
      patients at the age between 38 and 76 years revealed that stress urinary
      incontinence symptoms regressed after TVT operation, as evaluated 7 days after
      the procedure. In 51.7% of patients anterior colpoplasty or colpoperineoplasty
      was performed simultaneously to TVT operation. Control studies were performed a
      month and six months after the operation. Recurrence of the symptoms was observed
      in 11.7% of the patients. Revealed data let us show that the efficacy of this
      procedure is very high and reaches 88.3%.

PMID- 14669456
TI  - Progress in certification of poliomyelitis eradication and in laboratory
      containment of wild poliovirus.

PMID- 14669457
TI  - Influenza.
AB  - Influenza A(H3N2) viruses are predominating and causing most outbreaks in North
      America (Canada and United States) and in some European countries (Finland,
      Norway, Portugal, Spain and the United Kingdom). A rising trend in influenza
      A(H3N2) activity has been observed. The only outbreak due to influenza A(H1)
      virus was reported in Iceland but has declined since week 45.

PMID- 14669458
TI  - Georgia's hospital CEOs discuss health care's "perfect storm".

PMID- 14669459
TI  - OIG signals change in policy on excess charge rules.

PMID- 14669460
TI  - Taking the lead on hospital performance data.

PMID- 14669461
TI  - [Management of the pediatric dental patient with seizure disorder: prevention and
      treatment of emergencies].
AB  - Seizures are not infrequent in childhood and may occur during dental treatment.
      Generalized seizures and particularly the Tonic-clonic (grand-mal) are the most
      hazardous and may induce self-injury, aspiration, and medical emergency as status
      epilepticus. The differential diagnosis of isolated seizure attack should
      consider hyperventilation, hyperglycemia, local anesthetic toxicity, and anoxia.
      The pediatric dentist should be aware of predisposing factors that may induce
      seizure attack in their patients. Proper precautionary measures could prevent the
      attack from occurring or at least reduce its consequences. The diagnosis as to
      the cause of the seizure, as well as providing proper management, could prevent
      further complications. This article presents the medical and dental history
      relevant for prevention of seizure attack in the dental chair, antiepileptic
      drugs with possible interactions with the dental treatment and management of such
      attack, should they occurs.

PMID- 14669462
TI  - [Respiratory emergencies in the pediatric dental clinic: prevention and
      treatment].
AB  - Emergency situations can occur in the Pediatric Dental Clinic. The purpose of
      this article is to focus on signs and symptoms of emergencies involving the
      airway, such as aspiration of foreign bodies, asthma attacks, obstruction of the
      airway as a consequences of physiological and pathological causes and sedation
      induced apnea. Preventive and diagnostic tools, and protocols are presented, as
      well as a schematic flow chart of the management of airway obstruction due to
      foreign bodies. A new classification of risk factors that considers the
      parameters of sleep apnea risk, tonsil size, sedation level, patient's health
      status and dentist's qualification is also suggested.

PMID- 14669463
TI  - [Emergencies evolving from local anesthesia in the pediatric dental clinic:
      prevention and treatment].
AB  - A wide range of drugs and dental materials may be used when providing treatment
      to children. Routine medical and dental history may not provide all the necessary
      information to prevent allergic reactions, since young patients may be exposed to
      some of these drugs for the first time in the dental chair. The dentist should be
      prepared through training to reduce and at the same manage unwanted side effects.
      This article focuses on the possible adverse reactions following injection of
      local anesthetics; mainly, allergic and toxic side effects. Signs and symptoms
      are described and differential diagnosis is considered. The limited and absolute
      contraindication for administering some common local anesthetics is presented and
      local anesthetic drug interactions and toxicity relevant to pediatric patients
      are reviewed.

PMID- 14669465
TI  - Teachings dentistry in the 21st century.

PMID- 14669464
TI  - [Management of the pediatric dental patient with metabolic and hormonal
      disorders: prevention and treatment].
AB  - Metabolic and hormonal disorders can compromise the safety of child undergoing
      dental treatment. This article focuses on type I Diabetes mellitus and adrenal
      cortex disorders, which are more common in children. The pediatric dentist should
      be fully aware of the child's medical status and modify the treatment plane
      accordingly. Special attention should be made to the management of the anxious
      child with or without the need for pharmacological management. This article
      presents schematic flow chart for treatment emergencies in the diabetic patient
      and also protocols of treating the child who suffers from primary or secondary
      adrenal insufficiency.

PMID- 14669466
TI  - [Not a clean situation at all].

PMID- 14669467
TI  - [Home nursing must be marketable].

PMID- 14669468
TI  - [Confrontation with difficult situations. The body--searched for in vain].

PMID- 14669469
TI  - [Coping concepts. Support after an accident].

PMID- 14669470
TI  - [Assessment instrument for nursing. More concepts, less intuition].

PMID- 14669471
TI  - [Health on the job. Less disability, more psychosocial problems].

PMID- 14669472
TI  - [The hired ironing lady].

PMID- 14669473
TI  - [Seeking the personal challenge].

PMID- 14669474
TI  - [Threat to survival of the smile].

PMID- 14669475
TI  - [4th Congress of Home Aid and Care. Staying in one's home need not become a
      luxury].

PMID- 14669476
TI  - [Continuous 12 hour work schedule. A controversial work model].

PMID- 14669477
TI  - [Defense of personal identity. Anesthesia: the patient at the heart of
      technique].

PMID- 14669478
TI  - [Relations between the care recipients and nurses. Auto-efficiency or urgency of
      resources].

PMID- 14669479
TI  - [Stoma therapist of Neuchatel].

PMID- 14669481
TI  - [110th volume of Dutch Journal of Dentistry 4. Application of dental implants
      during the last five decades: from subperiosteal to transosteal and endosseous
      implants].
AB  - An overview is presented on the development of the treatment with oral implants
      in the maxillofacial skeleton during the last five decades. This overview has
      been divided into three periods: subperiosteal frame implants, transmandibular
      implants and endosseous implants. The latter period is also marked by significant
      developments in reconstructive preprosthetic surgery of hard and soft tissues to
      enable reliable implant placement.

PMID- 14669482
TI  - [Identification of caries risk patients 1. An overview of predictive models].
AB  - The ability of dentists to select caries risk patients on the basis of what they
      see and know, varies considerably. There is a need for objective methods. Methods
      using bacterial counts and salivary tests appeared to be inferior compared to
      methods based on the caries experience of the patient. There are two models, Nexo
      and Dentoprog, using the caries experience as caries predictor. The well
      documented Nexo method does not predict caries increment, but gives the provider
      a tool to target preventive intervention to those patients in need. The Dentoprog
      method is accurate, but has only one level of caries risk, which is considered by
      most providers as too low and thus unpractical.

PMID- 14669483
TI  - [Identification of cries risk patients 2. A new method for the selection of
      caries active children].
AB  - This paper presents a method, which, on the basis of the caries experience,
      predicts the caries increment up to the age of 15 years. This method provides the
      best caries prediction so far available. By applying the principles of medical
      decision-making cut-off points of risk can be assessed, whereby children can be
      selected as at risk or not at risk. The method is applicable in child populations
      with different caries incidences and meets the requirements of accuracy. With the
      user-friendly method, more than 80% of the children at risk can be identified and
      selected.

PMID- 14669484
TI  - [Dental tours de force 3. Treatment of a fused tooth].
AB  - This article reports the treatment of a maxillary central incisor, which appeared
      to be a fused tooth with two separate immature roots. After hemisection, the
      mesial part of the tooth was removed and the remaining part was treated by a
      direct pulp capping with a flowable dentin-bonded composite. The central diastema
      was closed orthodontically. Follow-up after six and eighteen months revealed a
      healthy pulp and an undisturbed root formation. Finally, a review of the
      literature on the aetiology and treatment of fused teeth is presented.

PMID- 14669485
TI  - [The 90's: different thinking in the social dentistry].

PMID- 14669486
TI  - [Open your mouth...].

PMID- 14669487
TI  - [The 'van der Linden' retainer].
AB  - Normally, only the anterior teeth have to be retained after an orthodontic
      treatment. For that purpose, a lingually bonded wire is preferred in the mandible
      and a removable plate in the maxilla. The design of the Van der Linden-retainer
      is based on theoretical considerations and secures rigid fixation of the six
      anterior teeth with solid anchorage in that region. A retention plate should not
      be used to move anterior teeth. However, with instant corrections small
      improvements can be realized. The fabrication and clinical use of the Van der
      Linden-retainer is explained and illustrated.

PMID- 14669488
TI  - [Microstomia as a complication of scleroderma].
AB  - Scleroderma is a rare connective tissue disease of unknown origin. It is
      characterized by increased collagen deposition leading to fibrosis and
      degeneration of the skin and sometimes of internal organs. There are two main
      groups of scleroderma: circumscribed scleroderma and systemic sclerosis.
      Circumscribed scleroderma is limited to the skin and systemic sclerosis has
      involvement of internal organs. The main oral manifestation of scleroderma is
      microstoma, which is a limiting factor in oral selfcare and professional oral
      health care. A case report is presented of the treatment of a 15-year-old female
      scleroderma patient with microstoma.

PMID- 14669489
TI  - Oral health revolutionary. Interview by Jacob Lonsdale.

PMID- 14669490
TI  - Hysterectomy and women's health.

PMID- 14669491
TI  - Asbestos and the new regulations.

PMID- 14669492
TI  - Gene therapies for diabetes.

PMID- 14669493
TI  - Is your plant and equipment safe to use?

PMID- 14669494
TI  - Background influences on dietary choice in early old age.
AB  - The contemporary increase in life expectancy is opening up a new stage in the
      Life course--early old age. Diet during early old age makes an important
      contribution to disease prevention, the management of established disease and
      postponing the onset of physical dependency. Despite its importance, few
      specifically medical, dietary interventions have been designed for this age
      group. The presently reported study aims to supply background information for
      such an endeavour. Qualitative interviews have been conducted with people in
      early old age, sampled purposively from members of a longitudinal study cohort. A
      number of background influences on the dietary choices of the interviewees have
      been identified. Some of these influences are specific to the present generation
      of people in early old age, such as eating in NAAFI canteens during National
      Service. However, the more general categories of which they are a part will have
      enduring usefulness. The findings are discussed in relation to: future dietary
      advice; the potential for interventions in primary care; enhancing the policy of
      free school fruit and research on the next age cohort to enter early old age.

PMID- 14669495
TI  - Relationship between maternal nutrient intakes in early and late pregnancy and
      infants weight and proportions at birth: prospective cohort study.
AB  - Experimental studies indicate that fetal undernutrition programmes life-long
      physiology and disease risk. The objective of this study was to investigate
      relationships between maternal nutrient intakes in early and late pregnancy with
      birth weights, placental weights, and infant proportions at birth. A prospective
      cohort study set in a district general hospital in the east midlands of England
      considered the diets of 300 pregnant women recruited from an antenatal ultrasound
      dating scan clinic. Estimation of nutrient intakes utilised five-day food diaries
      in the first and third trimesters of pregnancy. Two hundred and four diaries were
      returned and analysed for trimester one and 176 for trimester three. Birth weight
      and infant head circumference at birth were unrelated to nutrient intakes in the
      first or third trimester of pregnancy. Placenatal weight was not related to any
      maternal nutrient intakes. Thinness at birth was associated with low
      contributions of carbohydrate to dietary energy (p = 0.036). The present study
      shows that maternal nutrition in well-nourished populations does not exert a
      strong influence upon fetal growth. These data suggest that reported associations
      between low weight, thinness or greater head circumference at birth and disease
      in later life are not attributable to the effects of maternal undernutrition.

PMID- 14669496
TI  - The pattern and factors associated with child spacing in eastern Saudi Arabia.
AB  - The aim of this cross-sectional study was to determine the patterns of child
      spacing/birth intervals in the Eastern Province of Saudi Arabia and the socio
      economic factors related to them. The study sample comprised nine to 10-year-old
      Saudi school children randomly selected from 14 schools in Khobar, Thoghba and
      Dhahran in the Eastern Province of Saudi Arabia. A two-stage sampling technique
      was applied and yielded a sample of 536 children. The SPSS programme was used for
      data analysis. The mean preceding and succeeding birth intervals of children in
      the study were 26.2 +/- 13.7 and 28.2 +/- 12 months respectively. The most
      important variables that were found to be significantly correlated with the birth
      intervals were maternal age, level of education, family size and breastfeeding.
      This is the first time birth intervals were studied for an urban area in Saudi
      Arabia and the Gulf region. The figures-obtained are essential for any planning
      of mother and child health interventions. Health team members need to know this
      information and the variables related to them in order to advise mothers. The
      figures are also essential in planning measures to reduce infant and child
      morbidity and mortality.

PMID- 14669497
TI  - Coronary heart disease prevention in Kolkata, India.
AB  - Studies have shown that Asian Indians, both in India and the UK, have a high
      prevalence of coronary heart disease (CHD). A diet rich in saturated fats and a
      secondary lifestyle are contributory factors. There is published data
      recommending dietary change as one measure for primary prevention of CHD in
      India. The aims of the study were to: Investigate patients' understanding and
      awareness of dietary measures in the prevention of CHD Advise patients on how to
      modify their diet, taking into consideration religious and financial constraints.
      Provide some answers to the questions which patients often have about CHD and its
      prevention. The project was carried out at the R G Kar Hospital, a government
      hospital in north Kolkata (formally Calcutta), West Bengal, in eastern India and
      at a general practice six kilometres south of the hospital. Patients admitted
      with angina, myocardial infarction, elevated serum cholesterol or a past medical
      history of diabetes mellitus or ischaemic heart disease, were identified. A
      questionnaire was devised containing a list of foods commonly used by those on
      Bengali food. Patients were asked to mark on the list, or report verbally, those
      they felt were suitable for them to eat. They were also asked about their daily
      food intake and advised as to how their diet could be modified. At the hospital,
      28 subjects were interviewed. Of the responses relating to identification of
      suitable foods 48% were found to be correct; of the responses identifying
      unsuitable foods 39% were correct. In general practice, 62 subjects were
      interviewed; 50% of the responses identifying suitable foods were correct whereas
      60% of the responses identifying unsuitable foods were correct. The study showed
      that there is a need for further patient education regarding the effects of diet
      on the heart. The study was of greater use in the general practice setting, which
      caters for a middle class population; this group is at greater risk of CHD due to
      their food habits and lifestyle. Lower classes are, however, also at risk but are
      less likely to consume many of the unhealthy foods simply on account of their
      higher price.

PMID- 14669498
TI  - The boss, the owner, the proprietor ... the food hygiene manager?
AB  - The ease of opening up a small food business in the UK, combined with training
      regulations for food handlers, together with the requirement to demonstrate food
      safety management systems may be an indication that managers need management
      training in addition to food hygiene training. Enforcement agencies, examination
      bodies and trainers could play a key part in helping managers to develop
      effective food safety cultures. They could encourage management, and food hygiene
      training and development, for small food business bosses, owners and proprietors.
      Some of the skills that are missing are identified and suggestions put forward
      that will benefit those who run small food businesses in the UK.

PMID- 14669499
TI  - [Your ultrasound diagnosis? Hypertrophic pyloric stenosis].

PMID- 14669500
TI  - [Testicular tumors--a current review].
AB  - Only 1% of all male tumors are testicular origin, but it is the most frequent
      neoplasia in younger men. Risk factors include cryptorchism and a positive
      personal history of testicular cancer. Testicular cancer is divided in germ cell
      cancer and non germ cell cancer, the latter accounting for about 5%. Germ cell
      cancer is classified in seminoma and nonseminoma. Usually the first clinical
      presentation is painless swelling. Afterwards ultrasonography is indicated and
      tumor markers should be analysed. The first therapeutic step is always a radical
      inguinal orchiectomy. The following treatment depends on the staging: wait and
      see, radiotherapy or chemotherapy. Testicular cancer is characterised by a good
      cure rate (98-100% early stages) or recurrence free survival (80-90% late
      stages).

PMID- 14669502
TI  - [Metformin and lactic acidosis--fact or fiction? A review of current data].

PMID- 14669501
TI  - [Effectiveness of therapeutic interventions in obesity].
AB  - Obesity is a chronic disease resulting from various genetic factors and
      environmental conditions (nutrition, sedentary life-style, psychological
      factors). The importance of prevention and therapy of obesity is emerging because
      of the high prevalence of metabolic complications. The first goal of any therapy
      must be a stabilisation of weight, followed by a reduction of body weight. Any
      intervention must be long-acting. Short-acting therapies (diets) result in a
      regain of body weight in over 90%. The most effective therapy is an integrative
      concept basing on: change of nutrition by reduction of fat and carbohydrate
      intake (daily deficit of 500-1000 kcal). psychotherapeutic approach, targeting a
      long-term change of eating-behaviour and life-style, avoiding guilt feelings.
      encouraging physical activity. Drugs (Orlistat, Sibutramin) may be helpful in
      selected cases as a part of a limited treatment, they do not replace changes in
      lifestyle. Surgical interventions (gastric banding, gastric bypass) can be
      considered in morbid obesity with the presence of metabolic complications, as
      they are the most effective way of weight reduction.

PMID- 14669503
TI  - [Chronic microhematuria with flank pain].

PMID- 14669504
TI  - Mapping QTL for traits associated with resistance to ferrous iron toxicity in
      rice (Oryza sativa L.), using japonica chromosome segment substitution lines.
AB  - A mapping population of 66 japonica chromosome segment substitution lines (CSSLs)
      in indica genetic background, derived from a cross between a japonica variety
      Asominori and an indica variety IR24 by the single-seed descent, backcrossing and
      marker-assisted selection, was used to detect quantitative trait loci (QTLs) for
      leaf bronzing index (LBI), stem dry weight (SDW), plant height (PH), root length
      (RL) and root dry weight (RDW) under Fe2+ stress condition in rice. Two parents
      and 66 japonica CSSLs were phenotyped for the traits by growing them in Fe2+
      toxicity nutrient solution. A total of fourteen QTLs were detected on chromosome
      3, 6, 7, 9, 11 and 12, respectively, with LOD of QTLs ranging from 2.72 to 6.63.
      Three QTLs controlling LBI were located at the region of C515-XNpb279, R2638
      C1263 and G1465-C950 on chromosome 3, 9 and 11, their contributions to whole
      variation were 16.45%, 11.16% and 28.02%, respectively. Comparing with the other
      mapping results, the QTL for LBI located at the region of C515-XNpb279 on
      chromosome 3 was identical with the QTL for chlorophyll content on a rice
      function map. The results indicated that ferrous iron toxicity of rice is
      characterized by bronzing spots on the lower leaves, which spread over the whole
      leaves, causing the lower leaves to turn dark gray and to product chlorophyll
      catabolites or derivatives which reduce cytotoxicity of some heavy metals, such
      as ferrous iron. Furthermore, the QTL for LBI, SDW and RDW located at the region
      of G1465-C950 on chromosome 11 is a major QTL. Whether the QTL for SDW, PH, RL
      and RDW at the region of XNpb386-XNpb342 on chromosome 6 is associated with
      resistance to ferrous iron toxicity need further studies. Our goal is to identify
      breeding materials for resistance to Fe2+ toxicity through marker-assisted
      selection based on the detected markers.

PMID- 14669505
TI  - [Analysis of additive and AE interaction effects of QTLs controlling plant
      height, heading date and panicle number in rice (Oryza sativa L.)].
AB  - Plant height (PH), heading date (HD) and productive panicle number (PN) are
      important agronomic trait in rice. Appropriate plant height, heading date and
      panicle number are prerequisites for the desired high and stable yield level in
      rice breeding programs. A recombinant inbred line (RIL) population consisting of
      304 individuals was derived from a cross between indica varieties Zhong156 and
      Gumei2, from which a linkage map consisting of 168 RFLP, SSLP, RAPD and RGA
      markers that distribute on all the 12 rice chromosomes was constructed, and
      covers 1447.9 cM of the rice genome. The parents and 304 F9 lines were grown in
      the paddy field in China National Rice Research Institute (CNRRI), Hangzhou,
      China in 2001. The experiments were carried out in two seasons followed a
      randomized complete block design. QTLMapper 1.01 was applied to detect QTLs and
      QTL x environment (QE) interaction for HD (heading data), PH (plant height) and
      PN (panicle number), and conditional mapping for PH and PN was performed as well.
      A total of 15 QTLs with significant additive effects were detected, among which 4
      QTLs had significant QE interaction. Ten QTLs with additive x additive epistatic
      effects for PH, HD and PN were detected, among which none showed significant
      epistatisis x environment interaction. These QTLs explained 12.12%, 1.38% and
      5.00% of the total phenotypic variance for PH, HD and PN, respectively, and
      contributions were generally lower due to the strong epistatic effects. In
      conditional QTL analysis, the numbers of QTLs showing significant additive and
      epistatic effects were 7 and 6 for PH, and 3 and 3 for PN, respectively. Among
      the QTLs having significant additive effects for PH, qPH7-2 showed both additive
      effects and QE interaction, qPH7-1 and qPH10 showed QE interaction only, and the
      remaining 4 QTLs showed additive effects only. Each of the 3 QTLs having
      significant additive effects for PN did not display significant QE interaction.
      No epistatic QE interactions was detected. In addition, conditional QTL analysis
      indicated that the expression of QTLs for PH and PN may vary depending on the
      QTLs for HD.

PMID- 14669506
TI  - [Isolation and characterization of two closely linked phenylalanine ammonia-lyase
      genes from wheat].
AB  - Two closely linked, highly homologous phenylalanine ammonia-lyase (PAL) genes
      located in one phage clone, PAL1 and PAL2, were isolated from a wheat genomic
      library by using a polymerase chain reaction (PCR) fragment of a wheat PAL gene
      as probe. The two PAL genes were located approximately from 7 kb apart and
      displayed 93% identity with the same orientation. Southern blot analysis with a
      PAL1 specific fragment as probe showed the presence of a multiple gene family of
      PAL in wheat. Northern analyses demonstrated a differential expression of PAL in
      two Chinese Spring near-isogenic lines upon infection with stem rust fungus
      Puccinia graminis. In the resistant Chinese Spring Sr11 isogenic line with the
      resistance gene Sr11 that is known to interact with the avirulence gene P11 from
      the stem rust fungus, an induced expression of PAL was observed 4 days post
      inoculation (d.p.i.), and a massive induction was evident 8 d.p.i. By contrast,
      in the susceptible Chinese Spring sr11 line lacking the resistance gene,
      induction of PAL was seen 6 d.p.i. and the expression level at 8 d.p.i. was
      similar to that observed in the resistant line at 6 d.p.i. In wheat suspension
      culture cells, treatment with either an elicitor isolated from the stem rust
      fungus or chitin oligomers could activate PAL gene expression within 2 h. The
      fungal elicitor appeared to be more active in early activation of the PAL gene
      than were chitin oligomers. These results demonstrated that wheat PAL played an
      important role in the induced resistance response upon infection with stem rust
      fungus at transcription level.

PMID- 14669507
TI  - [Genetic analysis of segregation distortion of molecular markers in maize F2
      population].
AB  - A genetic linkage map of maize was constructed using 150 SSR and 24 RFLP markers,
      with F2 population from an elite hybrid (Zong3 x 87-1). Among 174 markers,
      covering whole maize 10 chromosomes, 49 markers (28.1%) showed the genetic
      distortion (P < 0.05). Of the total segregation distortion markers, 11 markers
      (22.5%) deviated toward male parent, Zong3, while 12 markers (24.5%) deviated
      toward female parent, 87-1, besides 25 markers (51.0%) distorted to heterozygote.
      Only one marker distorted to both parents. Totally, 14 segregation distortion
      regions (SDRs) were detected among 9 different chromosomes. Four of them were
      located in near regions where gametophyte genes were mapped, indicating that
      segregation distortion may be caused by gametophyte genes partially. Two
      segregation distortion regions, SDR6-1 and SDR7-1, detected in this study, seemed
      to be new segregation distortion regions. In this paper, reasons for segregation
      distortion and effects of segregation distortion on genetic mapping and QTL
      analysis were discussed. Regarding to QTL analysis with single locus, segregation
      distortion would not affect QTL mapping, but regarding to analysis of digenic
      interactions for epistasis, the fewer distortion markers and larger size
      population would be needed.

PMID- 14669508
TI  - [Development and identification of a set of Triticum aestivum-Thinopyrum
      bessarabicum disomic alien addition lines].
AB  - In order to transfer the genes for salt tolerance and disease resistance from
      Thinopyrum bessarabicum into wheat, the hybrid progenies between T. aestivum cv.
      Chinese Spring and T. aestivum cv. Chinese Spring-amphiploid Th. bessarabicum
      were screened. A set of T. aestivum-Th. bessarabicum disomic addition lines was
      developed with the assistance of mitotic chromosome C-banding and genomic in situ
      hybridization (GISH), as well as GISH on meiotic M I chromosome preparations. The
      results indicated that all the wheat chromosomes in the lines remained unchanged
      karyotypically, while the added Th. bessarabicum chromosomes paired regularly in
      meiosis. The developed disomic addition lines were designated temporarily as
      DAJ1, DAJ2, DAJ3, DAJ4, DAJ5, DAJ6 and DAJ7 respectively. Determination of the
      homoelogous groups of the added Th. bessarabicum chromosomes and localization of
      the genes for salt tolerance and disease resistance are undergoing.

PMID- 14669509
TI  - [The application of RAPD technology in genetic diversity detection of Jute].
AB  - The fingerprints of 10 species including 27 accessions in genus Corchorus were
      investigated with the technique of RAPD. Twenty-five primers were screened from
      119 random primers, and a total of 329 DNA fragments were amplified ranging from
      0.3-3.0 kb, 253 (87.78%), which were polymorphic. The average number of DNA band
      produced by each primer was 13.16. UPGMA cluster analysis and Nei's similarity
      coefficients were carried out and a dendrogram was constructed using software
      Biol D++. The results showed as follows: (1) There were abundant genetic
      diversities among 15 wild species and 12 cultivated species in Corchorus with
      genetic similarity coefficients ranging from 0.49-0.98. (2) The accessions could
      be clustered into three groups at cultivated species, and their close wild
      species were obviously different from wild species genetically. (3) At the level
      of D = 0.850, 27 accessions of Jute could be classified into ten groups,
      including C. sestuans, C. tridens, C. fascicularis, C. psendo-olitorius, C.
      psendo-capsularis, C. tilacutaris, Tian Jute (untitled), C. capsularis, C.
      olitorius and C. uriticifolius. Among which C. capsularis presented closer
      relationship with C. olitorius and further relationship with C. uriticifolius.
      The results matched well with that of the morphologic classification. (4)
      According to the molecular cluster tree, C. uritifolius, Chinese Tina Jute
      (untitled) and C. aestuans were at the basic level, revealing that these three
      species could be the primary wild species of Jute. (5) The tree also showed that
      C. tilacularis 21C from Africa could be a ecological subspecies of C.
      tilacularis, whilst niannian cai, ma cai and zhu cai collected different
      ecological types of C. aestuans, C. capsularis from Hainan was a close wild
      species of round fruit Jute cultivated species, and three species of C. olitorius
      collected from zhangpu, Henan and Mali were close wild species of long fruit Jute
      cultivated species. (6) within two cultivated species, the genetic similarity
      coefficients in round fruit cultivated species was higher than that of in long
      fruit cultivated species.

PMID- 14669510
TI  - Comparison of the method establishing embryonic stem cell lines from five
      different mouse strains.
AB  - We compared the characteristics of the method establishing embryonic stem cell
      lines from five different mouse strains using the medium containing 70% rat heart
      cell-conditioned medium (RH-CM) as ES cell culture medium, using the primary
      murine embryo fibroblast as feeder cells, and using the digestive enzyme buffer
      containing 1% chicken serum and "the series digestive method". We first reported
      new ES cell lines established from the outbred strain mice KM and ICR using the
      improved method in our lab and the ratio of establishment of ES cell lines from
      KM and ICR strain mice is up to 12% and 42.1% respectively. Compared with routine
      method of establishing ES cell lines, the improved method made distinct
      differences, increasing the ratio of ES cell line's establishment of 129/ter
      mouse from 11.8% to 33.3%, that of C57BL/6J mouse from 3.7% to 13.3%, that of
      BALB/c mouse from 2.9% to 19.4%. We tested the appropriate dispersing occasion,
      that is proliferating period of the ICM, affected the formation of ES clones and
      the ratios of ES cell lines established. It was shown that the most appropriate
      dispersed occasion for the ICM of 129/ter, C57BL/6J, BALB/c, KM and ICR mice was
      4-6 d, 3-3.5 d, 4 d, 4-5 d, 4-5 d after ICM proliferation respectively. At the
      same time, the effects of the concentration of digestive enzyme buffer were
      discussed. It was found that the ES cells from BALB/c mice were sensitive to the
      high concentration of digestive enzyme buffer and the 0.05% Trypsin-0.008% EDTA
      is an ideal concentration for their establishment and maintenance. It was shown
      that 'the series dispersed method' was much better than 'the once dispersed
      method' on the aspect of dispersing the proliferating ICM and formation of ES
      clones. Compared with the routine ES cell culture medium containing mLIF, the RH
      CM not only remarkably inhibited the differentiation of murine ES cells and
      maintained their diploid karyotype, but also promoted the attachment and growth
      of ES cells. This improved method of establishment and culture of ES cell lines
      effectively maintained a series of their characteristics of pluripotent embryonic
      stem cells.

PMID- 14669511
TI  - [Molecular cloning and expression in cryptorchid testis of SRG2 from a mouse
      testis spermatocyte apoptosis-related gene].
AB  - It was observed that the spermatogenic cells apoptosis dramatically increased in
      infertile man. Cloning of novel spermatogenic cell-specific gene related to
      apoptosis is of momentous physiological and pathological significance to
      illustrate the apoptosis mechanism and the biology process of spermatogenic
      cells. A novel mouse gene full-length cDNA sequence-SRG2 was identified (GenBank
      accession number AF395083), which was significantly changed in cryptorchidism,
      from a mouse testis cDNA library using a cDNA fragment (GenBank accession number
      BE644542) as an electronic probe. SRG2 was 1,088 bp in length. The putative
      protein encoded by this gene was 295 amino acids with a theoretical molecular
      weight of 33,579 kDa and isoelectric point of 9.64. The sequence shared no
      significant homology with any known protein in databases except TSARG2, with
      which its homology was 78%. RT-PCR showed that SRG2 was expressed significantly
      in testis. Using molecular beacon probe to examine the mRNA expression level of
      SRG2 gene in cryptorchid testis of various stages, we found that the gene was up
      regulated distinctly. Therefore, we conclude that this gene plays an important
      role in cryptorchid testis.

PMID- 14669512
TI  - [Studies of the relationship of melanocortin receptor 1(MC1R) gene with coat
      color phenotype in pigs].
AB  - Although coat color in pigs has no direct relation with economic traits, it
      affects economic benefit significantly, coat color selection are widely used in
      pig breeding and production. PCR-Acc II-RFLP, PCR-BspH I-RFLP and PCR-SSCP were
      used in combination to analyze genotype at MC1R locus among individuals from 16
      full-sib pedigrees and 6 Chinese native breeds including Jinhua, Jiaxing Black,
      Yushan Black, Leping Spotted, Shanggao Spotted and Shengxian Spotted pig. It was
      found that the Chinese native pig breeds carry a dominant black allele at MC1R at
      high frequency, this ED1 allele was suggested to be the major allele controlling
      black coat color in Chinese native pig breed. In addition, the evidence for a new
      allele was obtained in Shengxian Spotted pigs by PCR-SSCP analysis. It was
      reconfirmed from the result of pedigree analysis that ED1 was dominant over EP
      and e, while EP was incompletely dominant over e.

PMID- 14669513
TI  - [Characterization of novel alleles and new mutation sites of porcine MHC class II
      DQA].
AB  - The primers, DQAp161 and DQAp443, were designed based on the homologous region of
      SLA-DQA cDNA sequences and HLA-DQA genomic sequences. The 731 bp fragment of SLA
      DQA including completed intron 2, the near completed exon 2 and partial exon 3
      was obtained by PCR. The nucleotide sequences of the fragment of SLA-DQA were
      obtained with cloning and direct sequencing. Both nucleotide sequences of exon 2
      and amino acid sequences of alpha 1 domain were analyzed in a pedigree. The
      sequence data were compared with all sequences of SLA-DQA exon 2 in GenBank. Two
      novel alleles, DQA-SLT 26 and DQA-TC 21-1, were found according to the above
      analyses. Four amino acid changes were observed among SLA-DQA haplotype c, d and
      DQA-SLT 26. They were Val-->Ala(60), Lys-->Glu(65), Asp-->Gly(81) and Lys-
      >Ile(93). Comparing the amino acids sequence of the all SLA-DQA sequences with
      DQA-TC 21-1 revealed that the His (94) was changed into Tyr.

PMID- 14669514
TI  - [Cloning and analysis of three genes encoding type II CHH family neuropeptides
      from Fennropenaeus chinensis].
AB  - On the basis of sequence similarity, the crustean hyperglycemic hormone (CHH)
      family peptides have been classified into two types of hormones: type I and type
      II. Molt-inhibiting hormone (MIH) is a neuropeptide member of type II CHH family.
      Molting in shrimp is controlled by MIH and ecdysone. By inhibiting the synthesis
      of ecdysone in the Y-organ, MIH indirectly suppresses the molting activity of
      shrimp. In this study, we reported the cloning and characterization of 3 gene
      fragments encoding type II CHH family neuropeptides of the shrimp Fennropenaeus
      chinensis. According to the complementary DNA sequence of the mult-inhibiting
      hormone of Fennropenaeus chinensis, 3 primers were designed and synthesized. MP1
      and MP2 are sense primers, and MP3 is anti-sense primer. Polymerase chain
      reaction was performed using genomic DNA of Fennropenaeus chinensis as template.
      Three PCR products were obtained using primers MP1 and MP3. Their sizes are about
      600 bp, 850 bp, 1050 bp, respectively. A 580 bp PCR product was obtained using
      primers MP2 and MP3. All the 4 PCR products were cloned into pMD18-T vector. The
      recombinant clones were sequenced using ABI 310 Genetic Analyzer. After
      sequencing, all the DNA sequences were searched in the GenBank by Blast program
      to find similar gene sequences. The searching results revealed 3 DNA fragment
      sequences were of high similarity with CHH family neuropeptide genes from various
      crustean species. The 3 DNA fragments were named as NP1, NP2, and NP3. Their
      sizes were 540 bp, 601 bp, and 826 bp, respectively. Using the mRNA sequences
      with the most similarity to the 3 sequence fragments as reference, the gene
      structure of the 3 DNA fragment sequences was analyzed. The exons of 3 sequence
      fragments were aligned with their similar sequences by Clustal W program. Both
      NP1 and NP2 consisted of 1 intron and 2 exons. NP3 consisted of 2 introns and 3
      exons. Sequence analysis suggested that these 3 products belonged to sequence
      fragments of neuropeptide gene of type II crustacean hyperglycemic hormone
      family. The exons of NP1, NP2, and NP3 had highest similarity respectively with
      mRNA of Pem-SCP-C2 and Pem-SGP-C1 both from Penaeus monodon, and FenchMIH from
      Fennropenaeus chinensis. The identities were 91.5%, 92.8%, 88.9%, respectively.
      The results suggest NP3 is a fragment of molt-inhibiting hormone gene of
      Fennropenaeus chinensis NP1 and NP2 are two fragments of neuropeptide genes of
      type II crustacean hyperglycemic hormone family, which were found in
      Fennropenaeus chinensis for the first time.

PMID- 14669515
TI  - [The effects of mutant site G81R of RAB5A on RAB5A function].
AB  - To study the effects of mutant site G81R of RAB5A, two antisense RNA of RAB5A
      G81R and RAB5A were inserted into pcDNA3. 1/V5-His TOPO expression vector, and
      transfected into Anip973, respectively, then detected the protein expressional
      level of RAB5A by Western blot. Finally, we synchronized Anip973 and the two
      transfected cells at G0/G1, released cells at G0/G1 by culture medium containing
      FBS, and sequentially analyzed the percentage of cells at G0/G1, S and G2/M by
      FCM. The expression of RAB5A may be completely blocked by the antisense RNA of
      RAB5A G81R, while the antisense RNA of RAB5A partially blocked expression of
      RAB5A. Furthermore, cell cycle of Anip973 was reciprocity to the protein
      expressional level of RAB5A. The antisense RNA of RAB5A G81R effectively blocked
      the expression of RAB5A in Anip973. Cell cycle was lengthened by blocking or
      reducing expression of RAB5A G81R.

PMID- 14669516
TI  - [Genetic analysis of a Chinese pedigree with congenital synpolydactyly].
AB  - Syndactyly is a limb malformation that shows a characteristic manifestation in
      both hands and feet. This condition is inherited as an autosomal dominant trait
      with reduced penetrance. Clinical presentation, in general, is complete or
      partial webbing between 3rd and 4th fingers. Syndactyly type I, II and III were
      mapped to 2q34-36, 2q31-q32 and 6q21-23.2 respectively. Syndactyly type II is
      named as synpolydactyly (SPD). Expansion of a polyalanine tract in the HOXD13
      gene is known to cause synpolydactyly. HOXD13 gene locates in the HoxD complex.
      Nine homologous genes (HOXD1, -D3, -D4, -D8, -D9, -D10, -D11, -D12, -D13) of HoxD
      complex locate on chromosome 2 in the order of HOXD1 to HOXD13, among which
      HOXD13 is closest to the centromere. Deletions and duplications in HoxD complex
      or its upstream regulator factors have been identified to cause hand heteroplasia
      and consequently lead to abnormity of finger number or abnormity of
      configuration. We performed linkage analysis in a kindred with autosomal dominant
      hereditary syndactyly. Tight linkage to markers on chromosome 2q31-q32 (maximum
      two-point lod score: 6.78 at recombination fraction theta = 0.00) was observed.
      Multipoint linkage analysis produced a maximum LOD score of 7.02. Haplotype
      construction and analysis of recombination events narrowed this locus to a 20.61
      cM region between markers D2S2302 and D2S315. No mutation was found in the coding
      region, the intro-exon boundaries, or part of the promoter region of HOXD13. Our
      result demonstrates that synpolydactyly locus in the Chinese Han Population is in
      the region of chromosome 2q31-q32 but a different causal gene can be involved.

PMID- 14669517
TI  - [Studies of the association between angiotensinogen gene regulation and cytokines
      in essential hypertension].
AB  - This study is to explore the association between M235T allele polymorphism of
      angiotensinogen (AGT) gene and cytokines using essential hypertension probands
      research method. In hypertensives and controls, polymerase chain reaction
      combined with restriction endonuclease digestion was used to detect the target
      genotype variation, and enzyme-lined immunosorbant assay (ELISA) was used to
      detect the cytokine concentrations (IL-1, IL-6, TNF). The results showed that in
      hypertensives AGT gene, TT genotype was 55.88%, MT 35.29% and MM 8.82%. The ratio
      of T/M allele frequency was 0.735/0.265. In controls AGT gene, TT genotype was
      47.46%, MT 42.37% and MM 10.17%. The ratio of T/M allele frequency was
      0.686/0.314. AGT gene 235 T allele frequency in hypertensives was slightly higher
      than those in controls. Furthermore AGT gene 235 TT genotype and T allele
      frequency in middle and high grade of hypertensives were significantly higher
      than those in mild grade. In subjects of AGT 235 T allele group, the
      concentrations of IL-1, IL-6 and TNF in hypertensives were significantly higher
      than those in controls. In subjects of AGT gene 235 M allele frequency, the
      concentrations of IL-1 and IL-6 in hypertensives were no significant than those
      in controls. No matter in groups more than 60 years old or less than 60 years
      old, the concentrations of IL-1, IL-6 and TNF in hypertensives were higher than
      those in controls. No matter in hypertensives or controls, there were no
      differences in concentrations of IL-1, IL-6 and TNF when comparing groups more
      than 60 years old with groups less than 60 years old. The study indicated that
      AGT gene TT genotype and AGT gene 235 T allele frequency may be an important risk
      factor for hypertension. The high frequency of AGT gene 235 T allele and the high
      concentrations of IL-1, IL-6 and TNF in hypertensives may cause hypertension
      developing. It is also suggested the cytokines may effect the transcription and
      expression of AGT gene 235 TT genotype in hypertension. The concentrations of IL
      1, IL-6 and TNF had nothing to do with age no matter hypertensives or controls.

PMID- 14669518
TI  - [Recombineering and its application].
AB  - Driven by the need of functional genomics, a homologous recombination-based,
      highly efficient genetic engineering system that termed "recombineering" has
      recently been developed. Recombineering has been defined as a genetic engineering
      with phage-encoded recombination function that utilizes short homologies, a
      convenient term to describe homologous-dependent, recombination-mediated, genetic
      engineering. The bacteriophage lambda Red recombination system has critical
      differences from standard E. coli RecA-dependent recombination pathway. The phage
      systems have unique advantage in that they can catalyze efficient recombination
      with very short regions of sequence homology (< 50 bp). Recombineering does not
      require construction of plasmid or phage DNA intermediates containing the
      appropriately pre-engineered homology segment. All that is required in vitro is
      the synthesis of standard oligonucleotides or construction of PCR products that
      provide the homology. Importantly, they function even in the absence of RecA.
      These approaches do not rely on the presence of suitable restriction site, and
      can be used to insert, delete, clone or substitute genomic DNA sequences at any
      desired position on a target molecule in Escherichia Coli. Recombineering also
      facilitates many kinds of genomic experiments difficult to be carried out. In
      this article, the bacteriophage lambda Red recombinase system, the progression
      and applications of this powerful new technique are reviewed according to the
      data published recently.

PMID- 14669519
TI  - Cortical electrical stimulation combined with rehabilitative training: enhanced
      functional recovery and dendritic plasticity following focal cortical ischemia in
      rats.
AB  - This study assessed the behavioral and dendritic structural effects of combining
      subdural motor cortical electrical stimulation with motor skills training
      following unilateral sensorimotor cortex lesions in adult male rats. Rats were
      pre-operatively trained on a skilled forelimb reaching task, the Montoya
      staircase test, and then received endothelin-1 induced ischemic lesions of the
      sensorimotor cortex. Ten to 14 days later, electrodes were implanted over the
      peri-lesion cortical surface. Rats subsequently began 10 days of rehabilitative
      training on the reaching task in 1 of 3 conditions: 1. 50 Hz stimulation during
      training, 2. 250 Hz stimulation during training or 3. no stimulation. No
      significant difference in performance was found between the 250 Hz and no
      stimulation groups. The 50 Hz stimulation group had significantly greater rates
      of improvement with the impaired forelimb in comparison to 250 Hz and no
      stimulation groups combined. Fifty Hz stimulated animals also had a significant
      increase in the surface density of dendritic processes immunoreactive for the
      cytoskeletal protein, microtubule-associated protein 2, in the peri-lesion cortex
      compared to the other groups. These results support the efficacy of combining
      rehabilitative training with cortical electrical stimulation to improve
      functional outcome and cortical neuronal structural plasticity following
      sensorimotor cortical damage.

PMID- 14669520
TI  - Motor cortex stimulation enhances motor recovery and reduces peri-infarct
      dysfunction following ischemic insult.
AB  - Recovery of motor function following stroke is believed to be supported, at least
      in part, by functional compensation involving residual neural tissue. The present
      study used a rodent model of focal ischemia and intracortical microstimulation
      (ICMS) to examine the behavioral and physiological effects of cortical
      stimulation in combination with motor rehabilitation. Adult rats were trained to
      criterion on a single pellet reaching task before ICMS was used to derive maps of
      movement representations within forelimb motor cortex contralateral to the
      trained paw. All animals then received a focal ischemic infarct within the motor
      map. A cortical surface electrode was implanted over the motor cortex. Low levels
      of electrical stimulation were applied during rehabilitative training on the same
      reaching task for 10 days and ICMS used to derive a second motor map. Results
      showed that both monopolar and bipolar cortical stimulation significantly
      enhanced motor recovery and increased the area of cortex from which
      microstimulation movements could be evoked. The results demonstrate the
      behavioral and neurophysiological benefits of cortical stimulation in combination
      with rehabilitation for recovery from stroke.

PMID- 14669521
TI  - Cortical stimulation improves skilled forelimb use following a focal ischemic
      infarct in the rat.
AB  - Improving functional recovery following cerebral strokes in humans will likely
      involve augmenting brain plasticity. This study examined skilled forelimb
      behavior, neocortical evoked potentials, and movement thresholds to assess
      cortical electrical stimulation concurrent with rehabilitative forelimb usage
      following a focal ischemic insult. Adult rats were trained on a task that
      required skilled usage of both forelimbs. They then underwent an acute focal
      ischemic insult to the caudal forelimb area of sensorimotor cortex contralateral
      to their preferred forelimb. During the same procedure, they also received a
      stimulation electrode over the infarct area and two depth electrodes anterior to
      the lesion to record evoked potentials. One week following the surgery, rats
      received cortical stimulation during performance of the skilled task. Evoked
      potentials and movement thresholds were also determined. Functional assessment
      revealed that cortical stimulation resulted in superior performance compared to
      the no stimulation group, and this was initially due to a shift in forelimb
      preference. Cortical stimulation also resulted in enhanced evoked potentials and
      a reduction in the amount of current required to elicit a movement, in a
      stimulation frequency dependent manner. This study suggests that cortical
      stimulation, concurrent with rehabilitative training, results in better forelimb
      usage that may be due to augmented synaptic plasticity.

PMID- 14669522
TI  - Post-infarct cortical plasticity and behavioral recovery using concurrent
      cortical stimulation and rehabilitative training: a feasibility study in
      primates.
AB  - Stroke is often characterized by incomplete recovery and chronic motor
      impairments. A nonhuman primate model of cortical ischemia was used to evaluate
      the feasibility of using device-assisted cortical stimulation combined with
      rehabilitative training to enhance behavioral recovery and cortical plasticity.
      Following pre-infarct training on a unimanual motor task, maps of movement
      representations in primary motor cortex were derived. Then, an ischemic infarct
      was produced which destroyed the hand representation. Several weeks later, a
      second cortical map was derived to guide implantation of a surface electrode over
      peri-infarct motor cortex. After several months of spontaneous recovery, monkeys
      underwent subthreshold electrical stimulation combined with rehabilitative
      training for several weeks. Post-therapy behavioral performance was tracked for
      several additional months. A third cortical map was derived several weeks post
      therapy to examine changes in motor representations. Monkeys showed significant
      improvements in motor performance (success, speed, and efficiency) following
      therapy, which persisted for several months. Cortical mapping revealed large
      scale emergence of new hand representations in peri-infarct motor cortex,
      primarily in cortical tissue underlying the electrode. Results support the
      feasibility of using a therapy approach combining peri-infarct electrical
      stimulation with rehabilitative training to alleviate chronic motor deficits and
      promote recovery from cortical ischemic injury.

PMID- 14669523
TI  - Mapping individual brains to guide restorative therapy after stroke: rationale
      and pilot studies.
AB  - Some treatments under development to improve motor outcome after stroke require
      information about organization of individual subject's brain. The current study
      aimed to characterize normal inter-subject differences in localization of motor
      functions, and to consider these findings in relation to a potential treatment of
      motor deficits after stroke. Functional MRI (fMRI) scanning in 14 subjects
      examined right index finger tapping, shoulder rotation, or facial movement. The
      largest activation cluster in left sensorimotor cortex was identified for each
      task, and its center expressed in Talairach stereotaxic coordinates. Across
      subjects, each task showed considerable variability in activation site
      coordinates. For example, during finger tapping, the range for center of
      activation was 7 mm in the x-axis, 19 mm in the y-axis, and 11 mm in the z-axis.
      The mean value for center of activation was significantly different for all three
      coordinates for all pairwise task comparisons. However, the distribution of
      activation site centers for the finger task overlapped with the other two tasks
      in the x- and y-axes, and with the shoulder task in the z-axis. On average, the
      center of activation for the three motor tasks were spatially separated and
      somatotopically distributed. However, across the population, there was
      considerable overlap in the center of activation site, especially for finger and
      shoulder movements. Restorative therapies that aim to target specific body
      segments, such as the hand, in the post-stroke motor system may need to map the
      individual brain rather than rely on population averages. Initial details are
      presented of a study using this approach to evaluate such a therapy.

PMID- 14669525
TI  - Immunocytochemical localization of reelin in the olfactory bulb of the
      heterozygous reeler mouse: an animal model for schizophrenia.
AB  - Because heterozygous reeler (HR) mice share some abnormal traits with
      schizophrenic patients, and schizophrenia is often accompanied by impairment of
      olfactory function, this study examines reelin in the olfactory bulb of the HR
      mouse. In the WT mouse, reelin immunoreactivity is found in the extracellular
      matrix, and in the cytoplasm of olfactory nerve fibers, GABAergic interneurons,
      and glutamatergic mitral cells. Western blot analysis reveals that reelin
      immunoreactivity in the HR mouse is reduced by 45% compared to WT mouse. This is
      especially evident in the glomerular GABAergic interneurons. In WT mitral cells,
      reelin is found in discrete clumps near the axon hillock and within the axon. In
      the HR mouse, reelin axonal staining is diffuse and densely packed. In the
      rostral migratory stream of the HR mouse, immunolabeling shows an accumulation of
      reelin-containing neuronal precursors, apparently unable to shift from tangential
      to radial migration. These observations indicate that there is a downregulation
      of reelin in the HR mouse and suggest that secretion of reelin may be
      compromised. Further studies of the HR mouse may provide a new basis for
      understanding the role of reelin in the adult CNS, especially as it may relate to
      schizophrenia.

PMID- 14669526
TI  - Brain retraction injury.
AB  - This paper reviews the literature of the brain retraction injury during the last
      century. The review focused on the instrument characteristic as well as the
      physiopathological and histopathological damage of the brain induced by brain
      retraction. It was found that lesions were induced by cerebral ischemia. We
      conclude that a better monitoring system needs to be developed to avoid brain
      injury.

PMID- 14669524
TI  - Motor cortex stimulation for enhancement of recovery after stroke: case report.
AB  - We present a case report of a 65-year-old patient who had a subcortical infarct
      and a right spastic hemiparesis that occurred 19 months before being treated with
      an investigational therapy consisting of low frequency subthreshold epidural
      motor cortex electrical stimulation delivered during structured occupational
      therapy repeated daily for three weeks. Before treatment the patient's affected
      arm rested in a flexion posture and he was unable to flex or extend the fingers.
      After three weeks of treatment, the resting tone of his arm had improved and he
      was able to grasp a pen and write letters. The Fugl-Meyer motor scale score
      improved from 36 to 46 and this improvement was sustained for four weeks after
      the conclusion of rehabilitation therapy. This is the first patient to be entered
      into a randomized clinical feasibility and safety study assessing functional
      improvement in stroke patients treated with epidural cortical stimulation
      concurrent with occupational therapy (an investigational therapy).

PMID- 14669527
TI  - Temporal changes of neurogenesis in the mouse hippocampus after experimental
      subarachnoid hemorrhage.
AB  - Recent studies indicate the existence of progenitor cells and their potential for
      neurogenesis in the subventricular zone (SVZ) and the hippocampus dentate gyrus
      (DG) of normal adult mammalian brain. Increased neurogenesis has been shown
      following cerebral ischemia and traumatic brain injury; however, the involvement
      of neurogenesis in subarachnoid hemorrhage (SAH) has not been examined. Adult
      male CD-1 mice were subjected to SAH by endovascular perforation of the left
      anterior cerebral artery. Mice received intraperitoneal injections of the cell
      proliferation-specific marker 5'-bromodeoxyuridine (BrdU) after SAH induction.
      BrdU incorporation was examined from 1 to 30 days after SAH by
      immunohistochemistry. The BrdU-positive cells were detected in SVZ and DG of
      normal control brain, and were significantly decreased in both areas three days
      after SAH. The number of these cells had recovered to its control level seven
      days after SAH. Double staining with BrdU and NeuN indicated that the majority of
      the BrdU-positive cells migrating into the granular cell layer of the DG became
      NeuN-positive 30 days after SAH. In conclusion, temporal changes of the
      neurogenesis as shown in the present study suggest that neurogenesis in the
      hippocampus may affect functional outcome after SAH. The induction of the
      neurogenesis can provide therapeutic value against SAH.

PMID- 14669529
TI  - Risk of recurrent intracerebral hemorrhages.
AB  - Intracerebral hemorrhage (ICH) occurs in about 10%-15% of all strokes, and
      hypertension and cerebral amyloid angiopathy (CAA) are the main underlying
      causes. There is often controversy regarding surgical evacuation especially in
      elderly patients. Follow-up of these patients and regulation of hypertension is
      important to prevent re-bleeding. The number of recurrent hematomas will increase
      with time of follow-up. We reviewed 968 patients with an ICH treated in our
      Department and 48 patients with recurrent hemorrhages (4.9%). The mean interval
      between the first and the second hemorrhage was three years (one month to 10
      years). Clinical outcome after a second hemorrhage was severe and only 50% of
      patients were operated on the second hemorrhage compared to 77% (37/48) of
      patients who were operated on the first hemorrhage.

PMID- 14669528
TI  - Serial magnetic resonance imaging in experimental primate stroke: validation of
      MRI for pre-clinical cerebroprotective trials.
AB  - Precise assessment of stroke outcome is critical for pre-clinical testing of
      cerebroprotective strategies. Differences in stroke volume measured by various
      magnetic resonance imaging (MRI) techniques are documented in humans, but not
      well described in experimental primate stroke. This study characterizes changes
      in stroke volume using serial MRI scans in a baboon model of reperfused cerebral
      ischemia. The location/area of hyperintensity on MRI corresponded with the TTC
      stained infarct region. T2-weighted fast spin echo (T2W FSE), fluid attenuated
      inversion recovery (FLAIR), and diffusion weighted imaging (DWI) showed a
      decrease in infarct volume between 72 h and nine days post-ischemia (p = ns, p =
      0.029, and p = 0.006). T2W FSE and FLAIR demonstrated an increase in infarct
      volume from 24 h to nine days post-ischemia, while DWI displayed a decrease over
      the same period. While early T2W FSE, FLAIR, and DWI all correlated with late
      infarct volume (p < 0.001), 72 h T2W FSE was the best direct measure (2.39% +/-
      1.40% unity deviation). Serial MRI in a nonhuman primate model of focal cerebral
      ischemia recapitulates findings in clinical stroke. MRI at 72 h accurately
      predicts late infarct volume.

PMID- 14669530
TI  - Thrombosis and recanalization of symptomatic nongiant saccular aneurysm.
AB  - Complete thrombosis followed by recanalization of giant aneurysms is an
      infrequent process that has been exceptionally mentioned in relation to nongiant
      saccular aneurysms. A 25-year-old male presented with a right temporal hematoma
      and associated subarachnoid hemorrhage. Cerebral angiography revealed a small
      blister-like dilatation at the right middle cerebral artery bifurcation. The
      cerebral hematoma was surgically removed and a large thrombosed aneurysm was
      discovered and was wrapped. Follow-up angiography revealed complete
      recanalization of the aneurysm with preservation of all the arterial branches and
      the aneurysm was then completely occluded with detachable coils. This case
      provides insight into the well-known but poorly understood dynamic process of
      thrombosis and recanalization of cerebral aneurysms. The possible role of a
      cerebral hematoma in the pathogenesis of this process is discussed.

PMID- 14669531
TI  - Dural arteriovenous malformations of the skull base.
AB  - Dural arteriovenous malformations (AVMs) are interesting lesions, which can
      present as diagnostic and therapeutic challenges. Such AVMs were initially
      described as located solely in the dural venous sinuses, but during the last
      decade researchers have discovered them in other locations such as the tentorium
      and foramen magnum. It is understandable that they can develop in other locations
      because numerous arteriovenous shunts normally occur all over the dura. Early
      reports emphasize that they are congenital; however, some investigators have
      proposed that they are acquired lesions arising after sinus thrombosis and
      trauma. They also have variable clinical features. From 1975 to 2000 we treated
      400 AVMs, of which 46 were dural. Of these 46 dural AVMs, 18 could be classified
      as skull base AVMs. We restricted the designation of skull base AVMs to those
      AVMs located in the tentorium or adjacent to bones of the skull base. Two of
      these AVMs actually had their vascular nidus located in the bone. The common
      dural sinus AVMs were excluded from this category. The presenting clinical
      features of these skull base AVMs ranged from headache and pulsatile tinnitus to
      intracranial hemorrhage. They were treated by a combination of endovascular and
      microsurgical treatment. The majority of patients had a good clinical outcome.
      Skull base dural AVMs are an interesting clinical entity. Their clinical course,
      treatment and final outcome are variable depending on their location. They should
      be managed by a multidisciplinary approach.

PMID- 14669532
TI  - Up-regulation of cochlear aquaporin-3 mRNA expression after intra-endolymphatic
      sac application of dexamethasone.
AB  - The final aim of the present study is to see if the endolymphatic sac is really
      available as a drug delivery system to have effect on the inner ear organs. In
      the present study, we examined effects of a single insertion of dexamethasone
      into the rat unilateral endolymphatic sac on mRNA expression of the inner ear
      aquaporin (AQP) family, transmembrane water transporters and putative
      endolymphatic fluid modulators, by means of real-time quantitative PCR. Only AQP
      3 mRNA expression in the ipsilateral cochlea was significantly up-regulated in
      comparison with controls and the up-regulation was demonstrated both in dose
      dependent and time-dependent manners. These findings suggest that the intra
      endolymphatic sac steroids could make regulatory effects on the inner ear AQP-3
      expression via vestibular aqueduct and modulate the homeostasis of endolymphatic
      fluids, encouraging the possibility that the endolymphatic sac could be a
      therapeutic window for the inner ear disease.

PMID- 14669533
TI  - Prognostic value of interleukin-1 beta levels after acute brain injury.
AB  - Traumatic injury to central nervous system results in the production of
      inflammatory cytokines via intrinsic mechanisms by neurons, astrocytes and
      microglia, and extrinsic mechanisms by infiltrating macrophages, lymphocytes and
      other leukocytes. Interleukin-1 beta is the key mediator of the acute
      inflammatory host response. While this response is necessary for resolution of
      the pathologic event, the toxic nature of many of its products can cause
      significant tissue damage. We analyzed serum interleukin-1 beta levels by enzyme
      linked immunosorbent assay in 48 patients with solitary head injury who were
      transported to our clinic immediately after trauma. We categorized the patients
      according to their initial Glasgow coma scores in three groups, and compared
      their serum interleukin-1 beta values both with their Glasgow coma initial and
      outcome scores. This study helped to provide quantitative data to estimate
      clinical impressions and prognosis after head injury.

PMID- 14669534
TI  - A genotype of the polymorphic DNA repair gene MGMT is associated with de novo
      glioblastoma.
AB  - Glioblastoma is one of the most malignant tumors in humans. This tumor is thought
      to develop as a result of the accumulation of genetic abnormalities, mainly
      focused on the loss of heterozygosity on chromosome 10. O6-methylguanine-DNA
      methyltransferase (MGMT), which is one of the most important DNA repair proteins,
      has also been reported that enzymatic activity, as well as the methylation status
      of the promoter region of the MGMT gene, contributes to the therapeutic response
      of alkylating agents. We previously found three allelic variants in the MGMT gene
      and assayed the characteristics of these polymorphic proteins. We designed a case
      control study to investigate the role of MGMT genotypic risk factors for primary
      brain tumors. We compared the distributions of MGMT genotypes in primary brain
      tumors and normal controls. The frequencies of MGMT genotypes in examined primary
      brain tumors were not different from normal subjects. However, the combined
      heterozygote of V1 and a wild allele (V1/W) was frequently detected in de novo
      glioblastoma group with significant difference. Interestingly, among glial
      tumors, the V1/W genotype was dominantly detected in the patients with de novo
      glioblastoma. This study suggests that the V1/W genotype of the MGMT gene may
      contribute to the de novo occurrence of glioblastoma.

PMID- 14669535
TI  - Infratentorial intracranial pressure monitoring in neurosurgical intensive care
      unit.
AB  - Monitoring intracranial pressure (ICP) is an important element of neurosurgical
      critical care that is used primarily as an indicator of adequate cerebral
      perfusion. Such monitoring is usually done with intraparenchymal, subdural or
      intraventricular pressure sensor connected to a pressure transducer system. In
      the past, multiple studies have shown that there are certain pressure gradients
      between various intracranial compartments, especially if there is some focal
      intracranial pathological process. Several clinical and laboratory studies
      measured ICP inside the posterior fossa by placing the sensor into the cisterna
      magna or the cerebellopontine angle. None of them, however, monitored direct
      intraparenchymal pressure in the posterior fossa. Such measurement may be a more
      sensitive way to assess focal swelling, ischemia and tissue perfusion in the
      posterior fossa structures. We simultaneously monitored supratentorial ICP using
      an external ventricular drain placed in the lateral ventricle and infratentorial
      ICP with an intraparenchymal sensor inserted into the cerebellum. We subsequently
      analyzed data from five patients with different posterior fossa pathology each of
      which had simultaneous supra- and infratentorial ICP recordings for up to five
      days. We found difference in ICP between the infratentorial and supratentorial
      compartments and this difference changed over time. In this article, we discuss
      feasibility and safety of simultaneous infra- and supratentorial ICP monitoring
      in patients with the posterior fossa pathology.

PMID- 14669537
TI  - [Teenage pregnancy, a worldwide problem].
AB  - The incidence of adolescent pregnancy is highest in Sub Saharan Africa (143 per
      1,000 girls aged between 15-19 years). In Europe, it is well over 20 per 1,000.
      In the Netherlands, the percentage of teenage pregnancies ending in abortion is
      high (abortion ratio 61%), but the number of abortions among teenagers is low
      (abortion rate 8.6 per 1,000). Differences in the number of teenage pregnancies
      between industrialized countries are mainly caused by the availability of
      effective contraception for adolescents and not by differences in sexual
      behaviour. The main obstetric complication is preterm birth, especially if the
      interval between menarche and conception is short. Labour in teenagers is
      generally easier. Long-term socio-economic consequences for mother and child are
      great, in both developing and developed countries. There is an urgent need for
      programmes aimed at improving contraception in adolescents, especially in
      developing countries.

PMID- 14669536
TI  - [The effects of tamoxifen on the female genital tract].
AB  - Tamoxifen has both agonistic and antagonistic effects on the female genital
      tract, depending on the ambient oestradiol concentration and the menopausal
      status of the patient. In postmenopausal women tamoxifen has an oestrogen
      agonistic effect on the vaginal epithelium, the uterine myometrium and the
      endometrium. It may induce benign cystic hyperplasia of the endometrial stroma
      and cause an increase in poly formation. The risk of endometrial cancer increases
      2-3-fold after an exposure of up to 5 years. In asymptomatic tamoxifen users,
      gynaecological surveillance is not recommended. However, if there is
      postmenopausal bleeding, then transvaginal ultrasonography and histology of the
      endometrium are indicated. Tamoxifen can aggravate hot flushes and have a
      negative effect on sexual function. In premenopausal women, tamoxifen may induce
      ovarian cysts resulting in high serum-oestradiol levels. Oligomenorrhoea and
      amenorrhoea will occur in half of the patients. Tamoxifen has an antagonistic
      effect on the endometrium in premenopausal women and is associated with hot
      flushes and impaired sexual functioning. Teratogenic effects on the foetus have
      been described. Despite its gynaecological side effects, the benefits of
      tamoxifen in breast-cancer treatment outweigh the risks. Patients need to be
      informed about these side effects. Irregular or postmenopausal blood loss must
      always be reported to the treating physician.

PMID- 14669538
TI  - [Antiepileptic primidone shortly to be withdrawn from sale: change medication
      now].
AB  - The antiepileptic drug primidone is to be withdrawn from sale by January 2004.
      After this date, the drug will still be available for a time, but only on a
      limited basis. Most primidone users are elderly patients who have been prescribed
      this drug for many years. Changing to a new drug constitutes a health risk for
      them. If primidone treatment is discontinued too quickly, withdrawal seizures may
      appear, some of which may be severe. In patients who have not suffered an
      epileptic seizure for many years, discontinuing medication may be considered.
      Whenever continuation of anticonvulsive treatment is desirable, it may probably
      be a good idea to switch over to some newer antiepileptic drug. If a simple and
      quick substitution is essential, primidone may be replaced by its main
      metabolite: phenobarbital. General practitioners and neurologists are strongly
      advised to alter patients' medication in good time.

PMID- 14669539
TI  - [Diagnostic image (166). Sudden death in a young woman. Cyst of the pineal gland
      with a prominent cerebellar tonsillar herniation].
AB  - A 27 year-old woman died unexpectedly due to a cyst of the pineal gland with a
      prominent cerebellar tonsillar herniation.

PMID- 14669540
TI  - [Allogeneic stem cell transplantation following non-myeloablative conditioning:
      favorable results in 21 high risk patients with hematological malignancies
      treated in the Utrecht University Medical Center, the Netherlands].
AB  - OBJECTIVE: To describe the results of allogeneic stem cell transplantation after
      non-myeloblative conditioning in high-risk patients with a haematological
      malignancy. DESIGN: Prospective and descriptive. METHOD: In the Utrecht
      University Medical Centre 21 patients in an advanced stage of various
      haematological malignancies were treated with allogeneic stem cell
      transplantation following non-myeloablative conditioning. The patients were
      either younger than 55 but unsuitable for standard allogeneic stem cell
      transplantation because of co-existing disease, or between the ages of 55 and 70,
      and they had to have either a HLA-identical donor relative or a donor in which
      there was only one mismatched antigen. They were treated with a combination of
      fludarabine and a low dose of total body irradiation, followed by the
      administration of an unmanipulated stem cell transplantated. RESULTS: Engraftment
      of the stem cells was rapid in all patients but one, and 9 patients already
      showed complete donor cell chimerism 4 weeks after the infusion of stem cells. A
      total of 12 patients ultimately became completely donor chimeric, one of whom had
      received donor leucocytes; 7 patients were still mixed chimeric, with > 80% donor
      cells. 13 patients developed acute 'graft-versus-host disease' (GVHD), but in 10
      of these it was mild and transitory. After a median follow-up of 9 months, 5
      patients (24%) had died, 4 as a result of disease progression and one from a
      cause related to the transplantation. CONCLUSION: Allogeneic stem cell
      transplantation following non-myelaoblative conditioning is a convenient mode of
      therapy with a low mortality related to the transplantation. It is particularly
      suitable for the treatment of older patients at high risk with regard to their
      disease.

PMID- 14669541
TI  - [Evaluation and validation of a perinatal death audit by means of feedback to the
      caregivers].
AB  - OBJECTIVE: To evaluate a perinatal audit procedure by communicating the results
      to the caregivers (midwives and obstetricians) involved, in order to determine
      whether the audit led to specific suggestions for improving practice and whether
      evaluation of the panel assessments by caregivers leads to a different evaluation
      of the audit process. DESIGN: Descriptive evaluation study. METHOD: Because of
      privacy regulations, the results of a recently published audit concerning
      perinatal mortality were reported at an aggregated level. At their own request,
      two participating hospitals received panel assessment reports of their own cases.
      The audit procedure, the 77 panel assessments and the care provided were then
      evaluated during closed meetings with the caregivers affiliated to the respective
      hospitals. RESULTS: In two audited cases of mortality the caregivers judged the
      panel's assessments as being too light and as too severe in one other case
      (Cohen's kappa: 0.98). Detailed case description was considered essential to the
      audit procedure. While aggregated reporting of audit results provides a general
      understanding of substandard factors in the care provided, feedback of results on
      an individual practice level led to specific suggestions for improvement (in
      relation to medical aspects, patient-caregiver relationship and collaboration
      between caregivers). Lack of anonymity appeared not to be an issue for the
      caregivers. CONCLUSION: The feedback of perinatal audit results to the caregivers
      involved as well as discussion of these results led to specific starting points
      in the areas of collaboration, documentation and policymaking at both individual
      and institutional level.

PMID- 14669542
TI  - [A painful skin disorder in two newborn babies: neonatal subcutaneous fat
      necrosis].
AB  - Two newborn infant girls, both born after a complicated delivery, developed
      painful skin lesions. They were diagnosed with subcutaneous fat necrosis of the
      newborn. This is an uncommon and often very painful skin condition of which the
      aetiology is unknown. These babies have erythematous red-purple firm and painful
      subcutaneous nodules of fat necrosis. The disease usually runs a favourable
      course, treatment consisting mainly of supportive measures and adequate pain
      relief. However, thrombocytopenia and hypercalcaemia are complications which may
      be life-threatening if not treated adequately. Both neonates developed
      thrombocytopenia and symptomatic hypercalcaemia. Both newborns recovered after a
      prolonged period of hypercalcaemia but were left with scars.

PMID- 14669543
TI  - [Psychiatric symptoms during isotretinoin therapy].
AB  - A 22-year-old man with a known bipolar disorder was admitted to a psychiatric
      department for depression and suicidal ideation. He was being given isotretinoin
      to treat acne conglobata. During admission, he committed suicide. In the
      literature, isotretinoin is associated with the emergence of psychiatric
      symptoms. Although any casual relationship has not been identified, such a
      relationship cannot be ruled out. Methodologically well-performed research is
      lacking. However, positive dechallenge and rechallenge cases have been reported.
      Consequently, physicians must look out for the onset or worsening of psychiatric
      symptoms in patients treated with isotretinoin.

PMID- 14669544
TI  - [Determinants of hospital mortality in surgical patients aged 80 years and over].

PMID- 14669545
TI  - [Diagnostic importance of formic acid detection in methyl alcohol poisoning].
AB  - In the paper the authors have presented a possible use of formic acid detection
      in biological specimens in the diagnosis of methanol poisonings. Formic acid was
      determined as a volatile methyl formate ester by the gas chromatographic head
      space method. Based on opinions relating to methanol poisonings, formulated in
      the Forensic Medicine Department, Silesian School of Medicine, Katowice a
      potential application of the method mentioned above to forensic medicine was
      shown, especially in cases of late deaths after methanol intoxication and also a
      possibility of its use in clinical evaluation of the poisoning phase as well as
      monitoring the course of treatment.

PMID- 14669546
TI  - [Attempt to estimate risks of fatal poisoning on the basis of HCN and HbCO
      concentrations in blood of fire victims].
AB  - Using the results of HCN and HbCO concentrations in the blood of 174 deceased
      found in different burning spaces and 35 people with symptoms of poisoning
      evacuated from the scene of a fire and then admitted to hospital. The correlation
      between blood concentration of both these xenobiotics and death or chance of
      survival in a fire was estimated by statistical analysis. An attempt was made to
      define a value of so-called "cut-off" points for HbCO and HCN by independence
      test chi 2 with Yates's correction. Point and interval estimations (95%
      Comfield's confidence interval) were used for the odds ratio (OR). The research
      showed that there was a strict statistical correlation between the chance of
      survival and death risks dependent on blood concentrations of HCN and HbCO in all
      the groups examined.

PMID- 14669548
TI  - [Fatal poisoning due to narcotic abuse in the analytic-toxicological practice of
      Forensic Medicine Department Silesian Medical Academy in Katowice in years 1996
      202].
AB  - 147 cases of fatal poisonings in people due to narcotic abuse examined in the
      Forensic Medicine Department Silesian School of Medicine, Katowice in the years
      1996-2002 have been presented in the paper. In the group examined there were 126
      males and 21 females at the age of 16-44. Opium narcotics were found in 139 out
      of 147 cases and amphetamine derivatives in 18. Opiates were indicated in 58
      individuals and amphetamine only in 8. In 35 poisoned people opiates with
      barbituric acid derivatives were found. In 3 cases death resulted after taking
      opiates and amphetamine derivatives. 1 individual died after taking opiates and
      substances of the phenothiazine group. In the organic fluids of 18 people opiates
      and medicines being derivatives of 1,4-benzodiazepine and barbituric acid were
      found. Amphetamine and derivatives of 1,4-benzodiazepine were found in 6
      individuals and opiates, barbiturates, benzodiazepines and amphetamine in 1
      individual. Concentrations of all the substances indicated ranged widely and were
      as follows: < 0.10-17.40 > microgram/ml for opiates; < 0.24-30.00 > microgram/ml
      for amphetamine; < 0.12-1.90 > microgram/ml for 1.4-benzodiazepine derivatives
      and < 0.18-15.24 > microgram/ml for barbituric acid derivatives. Ethanol was
      found in 18 individuals and its concentration was < 0.2-2.5 >@1000.

PMID- 14669547
TI  - [Application of HPLC/MS for evaluation of fatal poisoning with digoxin in the
      aspect of medico-legal evidence].
AB  - This paper presents a case of suicidal poisoning of a woman with digoxin
      administered by injection. The autopsy of the subject was performed in the
      Institute of Forensic Medicine CMUJ. Body fluids (blood, urine, perylimph) and
      tissues (kidney, liver, brain) were collected for toxicological investigation.
      Digoxin determination was carried out by means of high performance liquid
      chromatography with mass spectrometry (HPLC/MS) which revealed digoxin in
      extremely high concentrations in specimens examined. The method is especially
      useful for analysis of cardiac glycosides in fatal poisonings for medicolegal
      purposes.

PMID- 14669549
TI  - [Polymorphism of the STR system LPL in the Silesian population].
AB  - This paper shows the results of locus LPL in the population of Upper Silesia. The
      examinations were performed in a group of 147 unrelated adults. The following
      gene frequencies were observed: LPL*9 = 0.0578; LPL* 10 = 0.4048; LPL* 11 =
      0.2517, LPL* 12 = 0.2449 i LPL* 13 = 0.0408. DNA was isolated using Blood DNA
      Prep Plus of A&A Biotechnology. Amplification was carried out in a Perkin Elmer
      GeneAmp PCR System 2400 thermal cycler, using the GenePrint STR System LPL (8p22)
      of Promega Corporation, Madison, WI, USA. PCR products were electrophoretically
      separated by high-resolution polyacrylamide gel--GDG of Perkin Elmer. Gels were
      stained by the silver method. Test chi 2, exact and Carmody's were used for
      statistical estimation. The identification values of the system are: PD, Ht, PM,
      MEC, PIC, MEP. The analysis of studies has shown that the examined population is
      in the genetic equilibrium conformable to the Hardy-Weinberg's principle. The
      estimated gene frequencies are similar to those observed in two Polish
      populations.

PMID- 14669550
TI  - [Population genetics of the 10 short tandem repeat (STR) loci in the population
      of Podlasie (Northeastern Poland)].
AB  - A population study on 10 STR loci: D3S1358, VWA, D16S539, D2S1338, D8S1179,
      D21S11, D18S51, D19S433, TH01 and FGA was performed on 620 unrelated individuals
      born in Podlasie (NE Poland). The DNA was amplified by multiplex PCR using a
      commercially available multiplex AmpFISTR SGM Plus kit. Capillary electrophoresis
      with fluorescent detection was carried out using the ABI 310 Genetic Analyzer.
      The expected performance of the analysed loci for personal identification and
      paternity testing was estimated. All loci met the Hardy-Weinberg assumption. No
      significant differences between the studied population and other Polish data were
      found. The combined values of the Matching Probability and of the Power of
      Exclusion are 4.18 x 10(-13) and 0.99997, respectively.

PMID- 14669551
TI  - [Remarks on operative regulations relating to decision making about inability to
      work in pension cases].
AB  - In years 1996 and 1997 both the Pension Act and the Social Insurance Act were
      changed in Poland and as a consequence of this, all the regulations relating to
      decision making about the inability to work. Having suppressed the so-called
      disability groups, such terms as permanent or temporary inability to work were
      introduced. Medical boards deciding on disability were replaced by predicative
      physicians working for the Social Insurance Department. Recently a rise in number
      of cases relative to the verification of the decisions passed by the SID and sent
      by either employer or Social Insurance Departments of district courts to the
      Department of Forensic Medicine Silesian Academy in Katowice has been observed.
      The authors have tried to analyse the cause of a rise in the number of appeals to
      a decision of the SID submitted by the insured.

PMID- 14669552
TI  - [Opinions on cases referring to: estimation of ability to participate in legal
      proceedings, estimation of ability to stay in conditions of imprisonment in the
      material of the Forensic Medicine Department, Silesian School of Medicine in
      Katowice in the years 1997-2002].
AB  - The legal and medical opinions referring to conditions of health of the
      participants of penal procedures: their ability to take part in legal
      proceedings, their ability to stay in conditions of imprisonment, are more and
      more common as an advisory practice of the Forensic Medicine Department in
      Katowice. It concerns the people connected with so called delinquency organized
      and people involved with economic crime. In the available literature there are no
      instructions relating to the description of the health state, which would be a
      contraindication (temporary or permanent) for partaking in legal proceedings or
      staying in conditions of imprisonment. In practice we observe a full freedom in
      dispensing of the medical documents and medico-legal opinions. The assumptions
      dating from 1997-2002, issued by the Department, were analyzed making allowances
      for age, sex, the kind of somatic diseases and the commissioning organs.
      Referring to obligatory regulations of the law, the authors introduce advisory
      principles accepted by the Forensic Medicine Department in Katowice in the above
      mentioned cases and attempt to estimate the divergence between judicial medicine
      experts with clinical specialties and forensic medicine experts.

PMID- 14669554
TI  - [Erroneous appraisal of X-ray examination results as the cause of improper legal
      classification of body injuries].
AB  - In the paper the authors presented three cases relating to erroneous appraisal of
      radiograms improperly classifying body injuries. In all these cases medico-legal
      opinions were given by experts appointed by the court but not at forensic
      medicine. In one case, the expert regarded only the result of the fibula
      capitulum fracture radiogram but he disregarded previous and further X-ray films.
      In another case, cerebral injury and subarachnoid hemorrhage were misrecognized
      by head computer tomography (HCT) as a result of unsuitable head position. In the
      last case, on the basis of routine radiograms a fracture of vertebra C2 was
      firstly misdiagnosed and verified as an anatomical anomaly in the structure of
      this vertebra. In these three cases conclusive medico-legal opinions changing the
      legal classification of the injuries experienced were provided by specialist
      scientific institutions of the Silesian School of Medicine in Katowice.

PMID- 14669553
TI  - [Superfecundation and superfetation with resulting heteropaternal twins--a
      possible resolution of the phenomena in the era of DNA typing].
AB  - In this paper a bibliography on superfecundation and superfetation phenomena and
      the author's opinion on the subject was presented.

PMID- 14669556
TI  - Finances. Vexing volumes.

PMID- 14669555
TI  - [Comprehensive medico-legal examination of an unidentified burnt victim NN with
      regard to individual identification].
AB  - In the paper the authors present results of the postmortem examination of the
      burnt body of an unidentified young man NN, who was suspected of being kidnapped,
      held in custody and finally burnt. During the autopsy dental identification was
      carried out and its results were compared to the dental card of the chosen man.
      Toxicological examinations of alcohol, CO, drugs and medicines were negative.
      Additionally, for individual identification, the analysis of blood DNA
      polymorphism was carried out in the following loci: CSF1PO, TPOX, TH01, F13A01,
      VWA, F13B, HPRTB, D16S539, D7S820, D13S317 (STR systems), D1S80 and also DQA1,
      LDLR, GYPA, HBGG, D7S8, GC. The results of the DNA polymorphism in the deceased
      were compared to those obtained in putative parents. Statistical analysis of the
      obtained results of the DNA analysis allowed to find out that the man NN was the
      son of H.E. and R.E. This comprehensive medico-legal examination allowed for
      identification of the deceased.

PMID- 14669557
TI  - Patient safety. Is your cell phone infecting patients?

PMID- 14669558
TI  - Hospital partnerships. Teaming up in Idaho.

PMID- 14669559
TI  - Work process. 'Welcome. You don't have mail'.

PMID- 14669560
TI  - Technology. Statewide data link.

PMID- 14669562
TI  - Hospice care. Final reunions.

PMID- 14669561
TI  - The data page. How committed are health care employees?

PMID- 14669563
TI  - Information technology. It's in the cards.

PMID- 14669564
TI  - Patient safety. Watch yourself.

PMID- 14669565
TI  - The value of benchmarking.

PMID- 14669566
TI  - Why small business is sick over health costs.
AB  - Overwhelmed by the cost of paying for health coverage, many small employers see
      their only options as cutting coverage, cutting staff or going out of business-
      any of which is bad news for communities and hospitals. There are creative
      alternatives to traditional insurance, and experts advise small businesses to
      explore those before taking drastic steps.

PMID- 14669567
TI  - Radiology [how technology breakthroughs are advancing the field].
AB  - Technology breakthroughs are reshaping radiology, speeding up the process,
      providing better definition of images and ultimately improving outcomes of care.
      This month's gatefold section provides an overview of the advances, with a
      particular focus on PACS.

PMID- 14669568
TI  - Telemetry takes off.
AB  - After a slow start, payers are signing on to the telemedicine trend, as rural
      hospital and major medical centers come to see the benefits of cooperation.

PMID- 14669569
TI  - Hospitalists. A specialty coming into its own.
AB  - In a decade, hospitalists have become fixtures at many hospitals. Proponents say
      they promote safety and efficiency, and free primary care docs from having to
      make rounds.

PMID- 14669570
TI  - Avoiding conflict of interest. How hospital boards can withstand close scrutiny.
AB  - With cynicism rampant over how business is conducted in the U.S., here's how
      hospital boards can protect themselves and their institutions from real or
      perceived conflicts.

PMID- 14669571
TI  - Time for a new social contract.

PMID- 14669572
TI  - [Health promotion benefits and obstacles as perceived by occupational medicine
      physicians in Poland].
AB  - This article presents the views of occupational medicine (OM) physicians
      concerning the following: (a) whether OM physicians should be involved in
      workplace health promotion: (b) whether they can benefit (if so in what way) from
      involvement in this activity; (c) whether they find the existing conditions
      favorable for launching health promotion projects; (d) what are the major
      obstacles? This paper is based on a survey carried out in the fall of 2002 in a
      group of 325 OM specialists who attend large groups of patients. Over 90% of the
      respondents believe that OM physicians should be involved in health promotion,
      however, one third of them do not plan any action in this field in the following
      year. Among the key benefits from health promotion, health gain is indicated by
      80% of OM physicians. Only a few respondents perceive their involvement in health
      promotion as an opportunity to be more competitive in health service market,
      thereby to increase their income. None of those interviewed thought that
      involvement in health promotion win them greater respect among peers. Almost 80%
      of the respondents complained about unfavorable conditions for carrying out
      workplace health promotion. As the most significant obstacles they reported the
      lack of interest in health promotion among employers (86% of respondents),
      unsatisfactory gratification (76%), limited skill to raise funds for health
      promotion (64%), limited opportunities to advance education in this field (59%),
      and the lack of interest in health promotion among employees (57%). In general,
      OM physicians express their willingness to advance their knowledge of health
      promotion, although 64% of respondents are convinced that they are well trained
      in this area. According to the respondents, a proper way to promote health is not
      only to become very active, but to commit employers to assure the development of
      health promotion at workplace and to allocate more funds for health promotion
      projects.

PMID- 14669573
TI  - [Occupational exposure to hazardous agents in enterprises supervised by the State
      Sanitary Inspection].
AB  - The presented data concern occupational exposure understood as work performed in
      working conditions with exceeded values of maximum allowable
      concentrations/intensities (MAC/MAI) of hazardous/noxious agents. In Poland, the
      State Sanitary Inspection (PIS) is responsible for the occupational hygiene
      surveillance in the work environment. Information on occupational exposure to
      various hazardous agents (chemical and physical, as well as industrial dust,
      lighting or microclimate) is collected by the Nofer Institute of Occupational
      Medicine every three years on the basis of routine statistics of sanitary
      inspectorates. Information on occupational exposure apply exclusively to workers
      employed in PIS-supervised enterprises. In 2000, the Polish enterprises,
      registered and supervised by PIS, employed 4 321 312 workers, including 505 638
      (11.7%) workers employed in working conditions with exceeded MAC/MAI values. In
      2000, both the proportion of workposts with exceeded MAC/MAI values and the
      proportion of workers employed in exposure decreased. The data show a general
      improvement in working conditions in Poland.

PMID- 14669574
TI  - [Assessment of risk of death due to malignant neoplasms induced by occupational
      exposure in a rubber footwear plant].
AB  - The main goal of the study was to analyze thoroughly the results of a cohort
      study. Such an analysis renders it possible to eliminate certain neoplasms as
      those not related to the observed exposure. The cohort study was carried out in a
      group of workers, covering 11,342 persons (5472 men and 5870 women), employed for
      at least one year during the years 1945-1985 in a rubber footwear plant. The
      cohort study was continued until the end of December 1997. Of all the sites of
      malignant neoplasms observed in the cohort, significant, exposure-related excess
      mortality was found to be due to malignant neoplasms of larynx and lung in men,
      and malignant neoplasms of gallbladder and lung in women. For these neoplasms,
      the values of observed risk among those exposed were significantly higher than
      among non-exposed. Moreover, in a certain interval of employment duration, an
      increase in risk rates with increasing duration of employment under exposure was
      observed, which suggests the presence of dose-response relationship. For all
      these sites, a relevant trend was shown by the RR values calculated in relation
      to the group of persons non-exposed but employed in the same plant. The internal
      reference group used to calculate RR values allowed to eliminate the effect of
      confounding variables, which is not always possible when the general population
      is used as the reference group.

PMID- 14669575
TI  - [Health effects of occupational exposure to cytostatics in medicinal personnel in
      the light of compulsory prophylactics: a cross-sectional study].
AB  - The aim of the study was to evaluate health effects of occupational exposure to
      antineoplastic drugs. The study group comprised 104 cytostatic-exposed health
      care workers employed in departments of chemotherapy; the control group consisted
      of 103 non-exposed workers employed in wards where cytostatics were not used. A
      questionnaire survey and routine laboratory assays (morphology, liver and kidney
      tests) were performed in all subjects. The exposed subjects reported hair loss
      significantly more frequently than controls (50.6% vs. 10.7%, respectively)
      Moreover, serious congenital defects were more frequent in the study group than
      in controls (4/84 pregnancies vs. 1/169 pregnancies, respectively). In
      conclusion, the results of the study did not reveal any significant differences
      in routinely performed tests between the subjects exposed to cytostatics and
      controls. This may be due to low sensitivity of laboratory tests or to the
      absence of health effects induced by antineoplastic drugs. Because of an
      increased frequency of congenital effects, women who plan conception should not
      be exposed to cytostatics or at least this group of women should use any possible
      individual protectors at work.

PMID- 14669577
TI  - [Binocular vision after treatment of retinal detachment].
AB  - The study covered 79 patients after treatment of retinal detachment. Double
      vision, strabismus and disturbances of eyeballs motility were found. Up to 12
      months after intervention, the deterioration of binocular vision was observed in
      48.28 to 89.66% of patients, depending on the method used. The majority of
      disturbances were observed during the first 3 months with tendency to gradual
      subsidence during consecutive 9 months. A patient, after treatment of retinal
      detachment, can be qualified to return to work where stereopsis is needed under
      condition that ophthalmologic examination is done every three months during the
      first year after operation and than once a year.

PMID- 14669576
TI  - [Most frequent causes of allergic contact dermatitis in farmers: based on
      material collected in the Nofer Institute of Occupational Medicine, Lodz].
AB  - Farmers are exposed to many skin damaging factors. Following dermatological and
      allergological examinations, in a group of 132 farmers with suspected
      occupational disease, contact allergy induced by metals (chromates, nickel,
      cobalt, mercury), disinfectants and their components (formaldehyde,
      glutaraldehyde, quaternary ammonium compounds, lysol, chloramine), rubber and
      pesticides, especially pesticides of thiophtalimide and thiocarbamate groups were
      recorded. Farmers also reacted to other chemical compounds (colophony, lanolin,
      propolis) rarely responsible for hypersensitivity in other occupational groups.
      In addition, extensive areas of dermatitis (13%) induced by irritating chemical
      (fertilizers, pesticides, fodder for breeding animals) and physical (changing
      temperature, humidity, effect of solar radiation) factors were observed in the
      study group.

PMID- 14669578
TI  - [Postgraduate studies in public health: the problem of efficiency evaluation].
AB  - The satisfaction of customer is the main measure and the most important,
      generally recognized criterion for evaluating the quality of products and
      services. In the case of education and training, the quality is frequently
      understood as effectiveness, i.e., the degree to what educational objectives of a
      training institution are met; the objectives previously formulated on the basis
      of analyzed and defined demands and expectations of customers (clients). In the
      first part of the paper: (1) the problems related to the question who in fact is
      the customer in the context of an institution providing education in public
      health are discussed; (2) a proposal for resolving these problems is presented;
      and (3) the main directions of evaluation activities, which should be undertaken
      under monitoring and effectiveness assessment of postgraduate training in public
      health are pointed out. In the years 1998-2002, the students' assessment data on
      educational programs, curriculum contents and subject teachers in the field of
      postgraduate studies in the School of Public Health, Nofer Institute of
      Occupational Medicine, Lodz, were collected with the help of specially-designed
      evaluation questionnaires. The data on the students' self-assessment of gained
      professional competencies were also collected. All students who completed the
      School of Public Health in these years were subjected to the evaluation
      inquiries. The data collected were analyzed. Due to the analysis it was possible
      to define: the quality of the curriculum contents, as well as the professional
      and didactic skills of the teaching staff as perceived by the students; the
      degree to what particular curriculum in public health contributed to the increase
      in professional competence as perceived by the students; the degree to what
      particular teaching subjects influenced the students' knowledge of and skills in
      Public Health. The results obtained provided information very useful in the
      teaching process, designing of educational programs and their modification.

PMID- 14669579
TI  - [A case of lung silicosis associated with plasmocytoma: the diagnosis and
      certification difficulties].
AB  - Silicosis is a chronic, progressing disease of the respiratory system. The aim of
      this paper was to describe a case of silicosis coexisting with not typical
      plasmocytoma. Silicosis was diagnosed in a 62-year old woman, after an 8-year
      employment as a grinder. The patient has suffered from progressing weakness,
      fatigue, and dyspnea for 2 years. The increased leucocytosis (18-20,000) and
      moderate lymphocytosis were found in laboratory tests. The patient was admitted
      to the hospital in a very serious condition, with fever and progressing
      insufficiency of the respiratory and circulatory systems. Following computed
      tomography (CT), tumorous silicosis was diagnosed in the Department of Internal
      and Occupational Diseases. After three months, the increased level of the whole
      number of serum proteins (until 90 g/l) was found for the first time together
      with few places of osteolysis in the x-ray cranium picture. The plasmocytoma
      infiltrations were found in the post-mortem lung examination. The described case
      seems to be interesting in view of a possible induction of monoclonal gammopathy
      by silicosis.

PMID- 14669580
TI  - [Conference of "Protection against electromagnetic fields 0-300 GHz in Poland-
      new regulations and perspectives and their harmonization with the European Union
      requirements" (Part II), December 16-17 2002, Lodz, Poland].

PMID- 14669581
TI  - [Limitations of occupational exposure to electromagnetic fields adopted by Polish
      law from the perspectives of international documents with particular reference to
      fields of low and medium frequencies].
AB  - Following the provisions of the decree on maximum admissible strength (MAS)
      values, issued by the Minister of Labour and Social Policy, comprehensive and
      homogeneous principles of workers' protection against excessive exposure to 0-300
      GHz electromagnetic fields have been in force since 2001. Different mechanisms
      responsible for interactions between electromagnetic field and human body, as
      well as the need to limit their harmful effects were taken into account while
      setting permissible exposure conditions. Owing to the fact that both the strength
      of electric and magnetic fields and exposure duration have been considered,
      Polish regulations facilitate a parallel harmonisation of the prohibited exposure
      levels with so-called "basic restriction" values adopted as a minimum protection
      level in many international guidelines and to implement a significantly higher
      level of workers' protection in case of long-duration per shift exposure
      (equivalent of "precautionary principle" applied in the evaluation of general
      public exposure). The approaches adopted in Polish regulations coincide in many
      points with a drafted EU directive. Amendments being introduced into Polish legal
      regulations on the environmental protection should maintain cohesion principle
      with legal regulations on occupational exposure to electromagnetic fields, and
      should take into account additional restrictions concerning the protection of
      residential areas, as practiced in many European countries.

PMID- 14669582
TI  - [Measurements of electromagnetic fields and evaluation of occupational exposure:
      PN-T-06580:2002 requirements and principles adopted in the European Union].
AB  - Under the process of developing a uniform system of protection against excessive
      exposure to electromagnetic fields, Polish metrological standards have been
      amended as an inherent complement of the modified decree on maximum admissible
      strength (MAS) values, issued by the Minister of Labour and Social Policy. Two
      parts of standard PN-T-06580:2002 were established by the Chairman of the Polish
      Committee for Standardisation in 2002. Of the whole range of frequencies covered
      by legal regulations, it laid down the principles of evaluation of occupational
      exposure to electromagnetic fields and radiation, providing precise definitions
      and rules for estimation actual dose and exposure factor in each case of exposure
      in real conditions. The standards also precise conditions, in which simplified
      principles of occupational exposure measurement and evaluation can be applied.
      Currently in the European countries, there are no general standards concerning
      methods of measuring and evaluating occupational exposure to 0-300 GHz
      electromagnetic fields. The provisions of numerous European (EN) and
      international (IEC) standards of a much narrower scope of application are similar
      to those formulated in standard PN-T-06580:2002.

PMID- 14669583
TI  - [Environment protection against electromagnetic fields. Legal point of view].
AB  - The author presents a concise information on the formal and legal status of the
      protection against the effect of electromagnetic fields in humans adopted in the
      European Union member states. Essential information on the Polish legal basis of
      the environmental protection against the effect of electromagnetic fields is
      provided. The most important, in the author's opinion, provisions of the
      Environmental Protection Law and executory provisions are discussed.

PMID- 14669584
TI  - [Problems with implementation of Polish standards on admissible electromagnetic
      field levels by the State Sanitary Inspectorate and of the measuring teams].
AB  - Amendments to Polish standards on electromagnetic fields (EMF) have made it
      necessary to modify the methods and procedures to be employed by the sanitary
      services responsible for monitoring occupational risks. To ensure a correct
      functioning of the State Sanitary Inspectorate and of the teams involved in
      measurements, it seems essential: to adjust other relevant regulations; to
      develop a method of classifying devices according to the emitted EMF; to provide
      uniform procedures to be followed in institutions if the measurements required by
      the regulations are not feasible; and to assemble a database on the determined
      levels of EMF emitted by various devices--especially those at frequency bands not
      yet monitored.

PMID- 14669585
TI  - [Biological effects and health risks of electromagnetic fields at levels
      classified by INCRIP ans admissible among occupationally exposed workers: a study
      of the Nofer Institute of Occupational Medicine, Lodz].
AB  - The aim of the study was to evaluate the effect of electromagnetic fields (EMF)
      on the workers' circulatory system, and to find out to what extent the EMF
      frequency, short-term (maximum values) and chronic (daily and lifetime doses)
      exposures influence the type of the observed disorders. The gathered data will
      help to evaluate whether hygiene standards that limit maximum admissible EMF
      values (e.g., ICNIRP standards) protect against adverse effects of exposure. The
      study covered workers employed in transformer and distribution stations, medium
      wave transmitting stations, radio-service and radio and TV multichannel
      broadcasting stations. In all the cases, exposure levels were considerably lower
      than those set as admissible according to the ICNIRP standards. Nevertheless
      changes in the circulatory system and a significant relationship between blood
      pressure and neurovegetative regulation disorders and exposure parameters were
      observed. The frequency of changes in the circulatory system was significantly
      dependent not only on the maximum EMF value, but also on its dose, which
      indicates that the hygiene standards for EMF cannot be limited only to short-term
      exposure maximum values, but they should be supplemented with dose-related
      standards.

PMID- 14669586
TI  - [Health protection of workers occupationally exposed to effects of
      electromagnetic fields in Poland and in the European Union member states].
AB  - Electromagnetic fields, one of potentially harmful physical agents present in the
      work environment in Poland, are under a constant surveillance regulated by the
      law. Among others, the surveillance involves periodical measurements of
      electromagnetic field (EMF) intensities in the work environment and medical
      prophylactic examination of workers at the employers' expense. The introduction
      of new MAC values imposes extra responsibilities on occupational health services,
      resulting from the need to verify the number of workers exposed to EMF at
      frequency bands corresponding with protection zones, and the need to set an
      appropriate range of prophylactic examinations, taking account of the current
      body of knowledge of biological effects of EMF and their hazards to workers'
      health. The suggestions how to change the range and frequency of medical
      prophylactic examinations are presented. The differences in occupational health
      care between Poland and the European Union members states, as well as changes in
      legal regulations on occupational diseases are discussed.

PMID- 14669587
TI  - Revision total hip arthroplasty: the influence of gender and age on the
      perioperative complication rate.
AB  - PURPOSE OF THE STUDY: Aim of this study was to report the incidence of
      complications in a consecutive series of revision total hip arthroplasties (THA).
      Gender and age as a risk factor for the occurrence of perioperative complications
      in patients undergoing revision THA were analyzed specifically. MATERIAL: All
      consecutive revision THA (n = 169) for aseptic loosening, which were performed
      between 1998 and 2002 were evaluated. Our study population had a mean age of 71.7
      years and consisted of 65.7% women and 34.3% men. Complete exchange of the
      primary implant was performed in 49.7% (84/169). The cup was replaced in 66 cases
      (39.1%) the stem only in 11.2% of patients (19/169). METHODS: Retrospective
      analysis was performed assessing the influence of gender and age on the
      complication rate by multiple regression models, estimating odds ratios (OR) and
      their 95% confidence intervals (CI). RESULTS: Comparable complication rates to
      those reported in the literature were found. Overall incidence of complications
      was 29.6% with a fracture rate of 6.5%, dislocation rate of 8.3%, nerve palsy
      rate of 4.7% and occurrence of thromboembolism in 1.8% of the reported cases.
      Mortality rate during the observed period was low (0.6%). We were not able to
      provide statistical evidence for the impact of gender and age on the complication
      rate. DISCUSSION: A comparable complication rate following revision THA to those
      reported in the literature was found in our study sample. Corresponding to other
      authors a higher risk of nerve palsy and thromboembolism among women was
      assessed. The observed correlation of fracture rates and female gender might be
      attributable to osteoporotic bone in postmenopausal women. Dislocation seemed to
      be more frequent in older patients, which has been described previously as well.
      Our low mortality rate in revision THA comparable to previous reports might be
      due to our short observation period. CONCLUSIONS: Revision THA is associated with
      a higher risk of complications than primary THA. A predictive value of gender and
      age in regard to the overall complication rate could not be confirmed which
      should be considered while deciding about the therapeutic strategy confronted
      with an aseptically loosened THA. To provide statistical evidence of a
      correlation between gender, fracture and nerve palsy as well as age and
      dislocation rates greater study populations are required.

PMID- 14669588
TI  - [Injuries of the atlas].
AB  - PURPOSE OF THE STUDY: Injuries of atlas account for 1-2% of all injures of the
      spine and for 7% of the injuries of the cervical spine. Fractures of atlas occur
      either as isolated fractures or in combination with the injury of the axis or
      occipital condyles. The aim of the work is to evaluate a group of patients with
      the injury of the atlas treated both conservatively and surgically. MATERIAL:
      Between January 1996 and October 2001 we treated at the Orthopaedic Department of
      3rd Medical Faculty, Carles University in Prague 10 patients with the injury of
      atlas. Between November 2001 and December 2002 we treated at the Orthopaedic
      Department and Spondylosurgical Department of the Medical Faculty Motol another 5
      patients with the injury of atlas. In 10 cases the fracture of atlas was isolated
      (anterior arch--once, 4 time Jefferson fracture, twice--fracture of massa
      lateralis), in 5 cases the fracture was associated with the injury of
      epistropheus (dens type II/posterior arch--twice, dens type II/Jefferson fracture
      -once, dens type II/massa lateralis--once, hangman fracture type II/posterior
      atlas arch--once). Teh group of patients included 9 men and 6 women of the
      average age of 46.6 years (range, 27-85 years). Eight patients were treated
      conservatively, 7 patients surgically. The most frequent cause of the injury was
      fall on the head or a severe downward violence in 7 cases, car accident in 4
      cases, other causes vere identified in 4 cases. Neurological deficit upon
      admission was found out only in one patient (Frankel D). METHODS: In isolated
      injuries of the anterior or posterior arch of atlas we always proceeded
      conservatively. The cervical spine was fixed for 12 weeks in the Philadelphia
      collar. One isolated fracture of massa lateralis was also treated conservatively
      for 12 weeks in the Philadelphia collar. Another case of the same type of
      fracture was treated surgically by C1-C2 by the Magerl technique supplemented on
      the intact side by the Gallie wire loop. Two stable Jefferson fractures were
      treated by the halo vest applied for 12 weeks. Two unstable fractures were
      handled surgically, once by C1-C2 by the Magerl technique and once by C0-C2
      occipitocervical fixation. C1-C2 associated injuries were treated in four cases
      surgically, three times by a direct dens fixation and once by C1-C2 fixation
      after Magerl supplemented with the Gallie wire loop. A patient with the
      associated hangman fracture type II and fracture of the posterior atlas arch
      refused the surgery and therefore was treated by the halo fixation for 12 weeks.
      Philadelphia collar was applied to the patients operated on. RESULTS: In the
      group of the conservatively treated, 3 patients complained of pain in the upper
      part of cervical spine and head requiring from time to time the administration of
      analgesics. All fractures healed within 12 weeks and the functional radiographs
      showed stable C0-C2 segments. As for complications, during the conservative
      treatment in one case a pyogenic secretion was recorded around the fixation
      elements of the halo apparatus requiring its removal after 8 weeks. The patient
      was further treated by a pelot fixation. In one case it was necessary to adjust
      twice the halo apparatus due to re-dislocation of the hangman fracture
      (associated hangman fracture of type II and posterior atlas arch). In spite of
      this the injury healed in C2-C3 subluxation, however, the fracture of atlas
      healed in a favourable anatomical position. In the group of the operated on, 2
      patients complained of pain in the upper cervical spine requiring from time to
      time the administration of analgesics and one patient complained of a marked
      limitation of the range of motion by 50% (C0-C2 occipitocervical fixation). Also
      in this group stable C0-C2 segments were found out 12-14 weeks after the surgery.
      DISCUSSION: In our group of 15 patients the fracture healed, i.e. stable C0-C1
      and C1-C2 segments, in all patients treated both conservatively and surgically.
      In the group of conservatively treated patients there occurred in one case re
      dislocation of the fracture. However, the patient refused the surgery repeatedly.
      Apart from these case we found in neither group any severe complication. The
      ratio of conservative and surgical treatment was 8:7. CONCLUSION: Based on our
      own experience and the literary data we believe that suitable for the treatment
      of stable injuries of the atlas is conservative treatment, i.e. fixation in the
      Philadelphia collar for 12 weeks. In unstable injuries or intraarticular injures
      with dislocation we prefer surgical fixation of C1-C2 or C0-C2 in dependence on
      the type of injury. All associated injuries are indicated for surgical treatment.

PMID- 14669589
TI  - [100 CT-guided pelvic operations].
AB  - PURPOSE OF THE STUDY: The authors present their 10-year experience with the
      computed tomography (CT) assisted insertion of implants in the sacroiliac (SI)
      region and acetabular region. Indications for these interventions and their
      detailed descriptions are reported. MATERIAL: A total of 98 patients, with the
      average age of 40.7 years and prevalence of men (70%), were treated. The most
      frequent cause of injury was a car accident, second in rank was fall from a
      height. Of these patients, 86 were followed up from 2 months to 3 years. METHODS:
      The surgical procedure was carried out in the CT department, in which conditions
      were provided to meet the criteria of an operating theatre. Computed tomography
      was used to plan the exact position of the implant and, during the procedure, to
      guide its precise insertion. These procedures required close cooperation of the
      surgeon and radiologist. A total of 73 CT-guided operations were performed on the
      SI region, using iliosacral screws or sacral rods. The operation was always
      preceded by surgery on the anterior pelvic segment. Iliosacral screws were also
      used in six patients operated on for pseudoarthrosis of the sacrum or chronic
      instability of the SI joint. The screws were also used in 19 patients who
      underwent surgical intervention in the acetabular region; in 14 cases it was for
      a fracture of the acetabular rim. All procedures were carried out by this minimal
      invasive technique. RESULTS: In all cases, correct insertion of the implant was
      achieved. There was only one serious preoperative complication due to the fact
      that the guidewire deviated from its planned direction without this being shown
      by CT scan. A late infectious complication following iliosacral screw application
      was recorded in one patient and, in another patient, a nut loosened on one side
      of the sacral rod. These implants, temporally immobilizing the SI joint, were
      removed at periods of 6 to 9 months after the operation. There was no case of
      secondary dislocation of the SI joint after the implant was removed. Complete
      bony healing of the fractures treated, including pseudoarthrosis, was achieved in
      all our patients. A comprehensive evaluation of the clinical results of CT-guided
      operations was difficult because of large inter-individual differences in the
      extent of pelvic injuries. DISCUSSION: CT-guided interventions are currently
      indicated predominantly for fractures of the sacrum or displacement of the SI
      joint up to a 15 mm distance. It is necessary to re-evaluate the extent of
      displacement after an exact reconstruction of the anterior pelvic segment and
      restoration of the anatomical conditions. The displacement in the posterior
      segment usually becomes markedly reduced. The simultaneous surgical treatment of
      both the anterior and posterior pelvic segments results in restoration of pelvic
      girdle continuity and maintenance of good stability of the pelvis. This permits
      early rehabilitation and mobilization of the patient. Other conditions indicated
      for CT-guided surgery include simple fractures of the acetabular rim with a
      distance between the fracture lines up to 7 to 10 mm, usually following hip
      dislocation, and simple oblique fractures of the acetabular columns. CONCLUSIONS:
      The CT-guided surgical procedure allows us to assess both the shape and course of
      fracture lines or distance between the injured structures. It also enables us to
      choose the optimal direction, in relation to these structures, for an implant to
      be inserted and to respect important anatomical structures in the surroundings.
      It helps us to determine the exact length of implants to be used. During the
      procedure, repeated CT scans facilitate checking the direction and position of
      both instruments and implants. In the closing phase of the operation, it is
      possible to assess closeness of the bones screwed together, the definitive
      placement of the implants and their reliable fixation. This method also permits
      to check whether a screw did not penetrate through the opposite cortical bone.

PMID- 14669590
TI  - Criteria for success with threaded cups (design, material and modularity).
AB  - PURPOSE OF THE STUDY: Over a period of three generations, threaded cups were
      developed and have become viable contemporary cementless hip implants. A few
      implants already have a high success rate over the mid and long term. Aim of this
      study was to evaluate contemporary threaded cups. MATERIAL AND METHODS: 30 of the
      second and third generation cups were systematically analyzed and measured using
      by a no-touch light section technique. Construction of inner form was determined
      with half sections. RESULTS: Approximately 50% have a conical shape, although
      there is a trend towards a more anatomical shape. 83% of the cups have a height
      up to 23% smaller than the radius. Only conical threaded cups have a relatively
      thin and constant wall thickness (1 mm-1.8 mm). Corundum blasted pure titanium,
      titanium alloys or HA coated implants are considered the standard materials. The
      insert is pre-assembled in two implants, otherwise the cups have modular inserts.
      Total ceramic inserts are found in four cups. Ceramic inserts with a sandwich
      construction are found in six cups. One cup has a full-metal insert. All other
      cups with metal-metal inserts have a sandwich construction. DISCUSSION: The
      studies by Kody (6) and our own studies (10) show that the V-cut threads have
      high values for turning moment and tilting stability. CONCLUSION: The screw-in
      behavior of threaded cups is largely determined by the design of the threads.
      Material and surface of threaded cups influence osseointegration and therefore
      long-term results. Contemporary threaded cups have a narrow V-cut and saw threads
      or flat threads with depths up to 3 mm, on average 4 turns, and pith values of
      approximately 4.5 mm. Three generations of threaded cups development were
      necessary to procure the current form with highly satisfactory mid- and long-term
      results.

PMID- 14669591
TI  - [Percutaneous aponeurotomy of the triceps surae muscle in cerebral palsy in
      children].
AB  - PURPOSE OF THE STUDY: To assess the short-term results of percutaneous
      aponeurotomy of gastrocnemius including the possible complications and effects of
      the treatment. MATERIAL: Totally 88 procedures were performed in 61 patients in
      the period 1998-2001. Re-examination in 2002 involved 44 patients with 66
      procedures. METHODS: The procedure was done from one-point incision. Six weeks
      immobilisation followed. Re-examination concerned the shape of the calf, the
      testing for palpable defect, US examination of calf muscles and aponeurosis,
      neurological and vascular examination. RESULTS: Recurrence of mild degree of
      equinus deformity was found in 3 out from 66 procedures. No neurological or
      vascular complications were registered. DISCUSSION: Rate of recurrence in this
      study is comparable with the figures after open aponeurotomy. CONCLUSION:
      Operation is reserved for skilled surgeon, however in short future, most of
      operations on spastics will be done like video-assisted procedures.

PMID- 14669592
TI  - [Total hip replacement in osteoarthritis with acetabular protrusion].
AB  - PURPOSE OF THE STUDY: The acetabular protrusion changes anatomical conditions for
      implantation of a cup in total hip replacement. The aim of this study was to
      evaluate different approaches to implantation of acetabular components in
      patients with this condition. MATERIAL: A total of 50 hips in 33 patients who had
      surgery for osteoarthritis with acetabular protrusion between 1992 and 2000 were
      evaluated. Their initial diagnoses were: idiopathic rotrusio acetabuli in 20
      patients, rheumatoid arthritis in nine, arthropathy due to psoriasis in two and
      Bekhterev's disease in two patients. The average age of the patients was 64.1
      years (range, 27 to 74 years). In group I including 18 hips, cemented polythylene
      cups were used (11 Poldi, 5 Ultima and 2 Weber prostheses). In group II involving
      32 hips, uncemented cups were employed (29 CLS, 2 Morscher and 1 Balgrist
      prostheses). Bone grafts inserted in the acetabular bottom were used in eight and
      25 cases of groups I and II, respectively. The mean follow-up was 7.1 years.
      METHODS: The following parameters were evaluated: Wiberg's angle, protrusion
      grades according to Sotelo-Garzy, Charnley scores, teardrop collapse, angle of
      acetabular inclination, approximate femoral head center and center of the femoral
      prosthesis head, and the distance between them in both horizontal and vertical
      directions, deviation of the center of the femoral component head from the
      anatomical center of rotation in horizontal and vertical directions, radiolucent
      zones according to de Lee and Charnley, position of the femoral head center
      inside or outside the TAR triangle and aseptic loosening of the acetabular
      component. RESULTS: At a follow-up of 7.1 years in group I, 10 hips showed full
      osteointegration, five underwent revision arthroplasty for aseptic loosening and
      three showed some degree of aseptic loosening. All failures occurred in the
      acetabular cups implanted without bone grafting of the acetabular bottom. In
      group II, 29 hips showed full clinical survival with complete osteointegration of
      the acetabular cup and three were found to have a radiolucent zone of 1 mm in
      width. DISCUSSION: The complete osteointegration of a cemented acetabular cup was
      achieved in 10 out of 18 hips, with eight having spongioplasty of the acetabular
      bottom. The use of uncemented cup resulted in full clinical survival and complete
      osteointegration in 29 cases out of 32. The best outcome was achieved with the
      use of an expansion, uncemented CLS cup. This is designed for peripheral
      fixation, which is useful in the protrusion of an acetabulum with a thin bottom
      and permits acetabular bottom grafting and positioning of the femoral component
      head in the center of hip rotation. It provides full osteointegration even with
      low bone quality. CONCLUSION: Prerequisites for successful arthroplasty in hips
      with acetabular protrusion include the firm implantation of an acetabular
      component, placement of the femur lateral to Kochler's line, location of the
      center of the femoral component head inside the TAR triangle and an agreement
      between the approximate center of the femoral head and the center of the femoral
      component head. The firm and lasting implantation of a cemented cup requires
      spongioplasty of the acetabular bottom. At an average of 7.1 years after surgery,
      uncemented cups in conjunction with bone grafting of the acetabular bottom showed
      better outcomes than cemented acetabular components.

PMID- 14669593
TI  - Arthroplasty in treating knee osteoarthritis and proximal tibia stress fracture.
AB  - The authors describe two cases of severely angulated tibial non-unions after
      proximal tibia stress fractures associated with ipsilateral osteoarthritis
      treated with modular knee endoprosthesis with a long tibial stem to stabilize non
      union fragments. During the procedure, no additional osteosynthesis or bone
      grafting was added. Both non-unions healed after 6 months with no post-operative
      complications. The authors suggest implantation of modular knee endoprosthesis,
      as a single procedure, in treatment of proximal tibia non-union after a stress
      fracture as a result of severe varus/valgus deformity. It provides a solution for
      osteoarthritis treatment, axis correction and non-union osteosynthesis.

PMID- 14669594
TI  - [An unusual case of non-structural scoliosis (case report)].
AB  - The case of a female patient with conversion scoliosis is described. At 24 years,
      the patient underwent surgery for herniated disks in the L4-L5 and L5-S1 regions
      and a short-time relief was achieved. At age 28, she was admitted to our
      department because of severe pain and antalgic posture. Because radiographs of
      her spine showed no findings corresponding to her symptoms, psychological
      examination was indicated. This revealed traumatic emotional experience in her
      family of origin and later also in her foster family, which unfavorably affected
      her married life. Psychotherapy, including cognitive behavioral treatment,
      hypnotherapy and audiovisual stimulation, markedly improved the patient's mental
      and somatic state during two periods of hospitalization. The effects of
      psychotherapy, physical therapy and adaptation of her physical activity regimen
      were still evident at 1 year after her therapy was commenced.

PMID- 14669595
TI  - [Simultaneous double interphalangeal dislocation on a single finger].
AB  - The authors report a rare case of the simultaneous double interphalangeal
      dislocation in the little finger of the left hand. A 35-year-old man, playing
      football as a goalkeeper, was injured when another player trod on his little
      finger. The dislocation was reduced by traction without anesthesia and the finger
      was immobilized on a splint. Although the patient removed the splint only a week
      later and failed to come for a check-up, at 1 year, his little finger showed no
      deformity and regained a full range of painless, active motion.

PMID- 14669596
TI  - [Traumatic avulsion of the tuberosity of the ischium].
AB  - The apophysis of the ischial tuberosity usually becomes united with the hipbone
      by 25 years of age. The highest incidence of avulsion in this region occurs
      between 15 and 17 years in young active persons. Apophysitis should be
      differentiated from apophyseolysis or an avulsion fracture of the ischial
      tuberosity. Apophysitis may be associated with chronic excessive sports
      activities in young men and women and is manifested by pain in the region
      involved. Its presence is confirmed by radiographic findings. The patient with an
      avulsion fracture of the ischial tuberosity reports an injurious event, usually a
      sudden movement during sports activities, associated with immediate pain. The
      diagnosis is again confirmed by radiology. Apophysitis is treated conservatively
      with no resulting problems. The poor healing of an avulsion fracture may result
      in chronic complaints, particularly painful sitting. This condition is treated by
      resection of the fractured apophysis. The authors describe the case of a 28-year
      old man who complained of experiencing pain when sitting. At 20 years of age, he
      suffered an avulsion fracture of the ischial tuberosity that was treated
      conservatively. He was examined at our department and an unhealed fracture of the
      ischial tuberosity was diagnosed by radiology and computed tomography. The
      separated bony fragment was removed and the patient was followed up to 1 year. He
      remained free from any complaints. An avulsion fracture of the ischial tuberosity
      is an injury rarely reported in our as well as foreign literature. The available
      case reports are discussed.

PMID- 14669597
TI  - [Chronic cardiac failure and non-insulin-dependent diabetes mellitus: coincidence
      or correlation?].

PMID- 14669598
TI  - [Functional state of the sympathetic-adrenal system at the stages of developing
      late complications of diabetes mellitus].
AB  - AIM: To study a functional state of the sympathico-adrenal system in patients
      with diabetes mellitus (DM) in developing late complications. MATERIAL AND
      METHODS: The study included 81 DM patients: free of late complications and
      diabetic autonomic neuropathy (DAN) (n = 24); with DAN (n = 6); with DAN and
      nonproliferative retinopathy (n = 8); with DAN and nephropathy stage 1-2; with
      DAN and diabetic retinopathy, sensory polyneuropathy (n = 23); with diabetic
      nephropathy stage 4 (n = 14). Blood levels of epinephrine, norepinephrine,
      dopamine were measured using liquid chromatography with electrochemical
      detection. A spectral analysis of the cardiac rhythm was made with application of
      the program "Mars". RESULTS: In patients with DM progression there was imbalance
      of autonomic nervous system, sympathetic hypertonicity, parasympathetic
      hypotonicity, subnormal power of the central regulatory contour. Dissociation was
      found between the degree of hypersympathicotonia and a fall of blood
      catecholamines concentration related to severity of the disease complications.
      CONCLUSION: Dissociation between sympathetic hypertonicity and low concentration
      of blood catecholamines is prognostically unfavourable and predicts development
      of arrhythmia and asystole. Augmentation of centralization of the systems
      regulating autonomic nervous system reflects tension of the regulatory systems
      and predicts disruption of adaptation.

PMID- 14669599
TI  - [Characteristics of functional status of the autonomic nervous system in patients
      with diabetes mellitus].
AB  - AIM: To evaluate prognostic significance of autonomic nervous system (ANS)
      dysfunction in patients with diabetes mellitus (DM). MATERIAL AND METHODS: The
      examination covered 51 DM type 1 patients aged 18 to 43 years with DM history
      from 6 months to 31 years. ANS function was assessed by spectral analysis of
      cardiac rhythm with calculation of indices of rhythm "rigidity", centralization
      and activity of subcortical centers. RESULTS: DM progression and development of
      its late complications were accompanied with dissociation of tonicity of the
      sympathetic and parasympathetic ANS components, augmentation of regulatory
      systems tension. Evidence was obtained for correlation of relative values of SW1
      power with severity of DM (r = 0.88) and its microvascular complications (r =
      0.70). Decreased power of MW2(%) in the tilt test predicts development of
      orthostatic hypotension. CONCLUSION: Involvement in the regulation of the central
      contour of ANS management reflects adaptation failure and is prognostically
      significant.

PMID- 14669600
TI  - [Characteristics of lipid profile in blood plasma of patients with metabolic
      syndrome and manifest disorder of carbohydrate metabolism].
AB  - AIM: To study specific features of lipid plasm profile in patients with metabolic
      syndrome (MS) and manifest disorder of carbohydrate metabolism (CM) as well as
      their relationships with clinical symptoms of MS. MATERIALS AND METHODS: Contents
      of lipids and apolipoproteins of plasm was measured on an empty stomach in 30
      patients (18 females and 12 males) with MS and manifest disorder of CM (diabetes
      mellitus type 2 at the stage of good and satisfactory compensation of CM without
      terminal complications). RESULTS: The patients were found to have a subnormal
      level of HDLP cholesterol, high levels of total cholesterol, LDLP cholesterol and
      LP alpha. Hypertriglyceridemia occurred only in 31.4% patients (TG < 200 mg/dl).
      Mean TG level was 173.69 +/- 21.52 mg/dl. TG and diastolic arterial pressure,
      fasting glycemia and waist circumference significantly correlated. If the WC/TC
      was 1.0 and higher, the antiatherogenic plasm factor--HDLP cholesterol-
      significantly lowered. Positive correlation existed between TG and total
      cholesterol, LDLP cholesterol, apoB, LDLP cholesterol/HDLP cholesterol,
      apoB/apoA1, while negative correlation was seen between TG and HDLP cholesterol
      levels. Patients with hypertriglyceridemia had significantly higher levels of
      total cholesterol, LDLP cholesterol, apoB, apoB/apoA1. CONCLUSION: Plasm levels
      of TG most significantly reflect severity of basic clinical manifestations of MS:
      abdominal obesity, arterial hypertension, CM compensation. The presence of
      hypertriglyceridemia in MS patients can be considered as an indicator of high
      atherogenic potential of plasm.

PMID- 14669601
TI  - [Syndrome of non-thyroid pathology in patients with cardiovascular diseases
      (review)].

PMID- 14669603
TI  - [Experience with ixel (milnacipran hydrochloride) use in the treatment of
      patients with post-stroke depression].
AB  - AIM: To evaluate antidepressive efficacy of ixel in patients with poststroke
      depression (PSD). MATERIAL AND METHODS: The study included 59 PSD patients aged
      43-79 years divided into two groups: the test group (31 patients) treated with
      antidepressive drugs and the control group (28 patients) was not treated with
      such drugs. The test group took a two-month treatment with oral ixel in a dose
      100 mg/day. The neurological status was assessed by Lindmark scale (LS), severity
      of depression-by Hamilton scale (HS). RESULTS: On ixel treatment day 10-14 the
      patients felt better, by the treatment day 60 depression disappeared in 60.9%,
      only borderline conditions were seen in 39.1%. Mean score by HS fell from 15.8 to
      5.7. The controls showed moderate reduction of some symptoms of depression, mean
      score by HS decreased insignificantly (from 14.5 to 13.4). By LS, significant
      differences between the groups were not registered. Side effects arose in 10
      patients, 6 of them withdrew. CONCLUSION: Ixel is an effective drug against
      depression in stroke survivors.

PMID- 14669602
TI  - [Characteristics of psycho-autonomic correlations and clinical course of ischemic
      heart disease in men and women].
AB  - AIM: To study psychovegetative correlations and clinical course of ischemic heart
      disease (IHD) in men and women. MATERIAL AND METHODS: Personality characteristics
      (MMPI test), reactive and personal anxiety (Spilberger's questionnaire), severity
      of depression (Back's questionnaire), vegetative status (vegetative disorders
      questionnaire), variability of cardiac rhythm (cardiovascular tests) were studied
      in 60 females and 62 males with IHD. RESULTS: IHD females vs males were
      characterized by higher neurotization, personal accentuation, more serious
      anxiety, depression and vegetative disturbances, lower variability of heart rate.
      IHD in females is more frequent in postmenopause, is characterized by less severe
      hemodynamically significant coronary stenoses. CONCLUSION: Emotional disorders
      make a great contribution to a course of ischemic heart disease.

PMID- 14669604
TI  - [Pyrazidol in the treatment of depression in patients with ischemic heart
      disease].
AB  - AIM: To study efficacy and safety of pirazidol administration in depressive
      patients with ischemic heart disease (IHD). MATERIAL AND METHODS: Pirazidol was
      given in a dose 0.15-0.3 g/day for 4 weeks to 30 IHD patients aged 21-65 years.
      21 of them had nosogenic depression, 9 patients had dysthymia. The efficacy of
      the antidepressive action was assessed by the Hamilton scale. RESULTS: The trend
      to a decrease in Hamilton scale scores was manifest by the end of the treatment
      week 2. To the end of the study the overall score median lowered from 17 to 9,
      most of the patients had the score sum under 11. Side effects were insignificant.
      In pirazidol combination with beta-blockers, blockers of calcium channels,
      antiaggregant, diuretic drugs, nitrates and other cardio- and angiotropic drugs
      unfavorable interactions were not registered. CONCLUSION: Pirazidol can be
      effectively used in the treatment of psychosomatic disorders in patients with
      cardiovascular diseases.

PMID- 14669605
TI  - [Concept and research strategy in quality of life studies in gastroenterology
      (review)].

PMID- 14669606
TI  - [Idiopathic thrombocytopenic purpura and gestational process (lecture)].

PMID- 14669607
TI  - [Gestational arterial hypertension. Mechanisms of formation. Treatment with
      normodipin].
AB  - AIM: To study endothelium-dependent vasodilatation (EDVD), plasma endothelin 1,2
      (ET-1,2) contents and urinary NO metabolites in normal pregnancy and various
      kinds of gestoses with evaluation of normodipine effects on blood pressure and
      EDVD. MATERIAL AND METHODS: 59 primigravidas 18-32 years of age (pregnancy terms
      34-39 weeks) were divided into three groups. Group 1 consisted of 23 women with
      arterial hypertension treated with normodipine in 11 of them. In group 2 sixteen
      pregnant women had edema and group 3 consisted of 20 women with physiological
      pregnancy. 12 non-pregnant women comprised a control group. RESULTS: In normal
      pregnancy ET-1,2 content was low while urine NO metabolites levels were high.
      This contributes to maintaining adequate reaction of the brachial artery in
      response to the "shiftstress". In women with edema the brachial artery response
      to short-term occlusion was decreased. In women with both high blood pressure and
      edema had vascular response paradoxically spastic with a two-fold decrease in
      blood flow rate, high plasma ET-1.2 contents and low urine NO metabolites levels.
      Normodipine in gestational arterial hypertension normalizes both blood pressure
      and EDVD. CONCLUSION: Endothelial dysfunction is an important factor predisposing
      to development of arterial hypertension. Monotherapy with normodipine (5 mg/day
      in a single daily dose) during 3 weeks is effective in controlling gestational
      hypertension.

PMID- 14669608
TI  - [Comparative analysis of the efficacy of iodine prophylaxis in pregnant women
      living in endemic goiter areas].
AB  - AIM: To assess efficacy of different methods of iodine prophylaxis in pregnant
      women living in conditions of goiter endemia. MATERIAL AND METHODS: Standard
      clinical, laboratory and device tests for iodine deficiency according to WHO
      criteria were made in 156 pregnant women living in the territory affected by
      goiter endemia. Of them, 121 examinees had no thyroid pathology, 35 ones had
      diffuse euthyroid goiter. All of them received different kinds of iodine
      prophylaxis. RESULTS: The occurrence of neonatal TTH values over 5 iU/l in
      neonates born by mothers free of thyroid pathology on potassium iodide
      prophylaxis when pregnant was 9.1%. This is much lower than in conventional
      iodine prophylaxis--17.24% (p < 0.01). A comparative analysis of the efficacy of
      potassium iodide-200 in pregnant women with diffuse euthyroid goiter and its
      combination with L-thyroxine has shown that by the effect on lessening frequency
      of neonatal TTH over 5 iU/l the above schemes do not differ significantly,
      thyroid reduction is more prominent in pregnant women on thyroxine with potassium
      iodide. CONCLUSION: The index of neonatal TTH is an objective criterium to
      control efficacy of different methods of iodine prophylaxis in pregnancy.

PMID- 14669609
TI  - [Lung biopsy in the diagnosis of causes of lung involvement in hemoblastosis].
AB  - AIM: To ascertain the role of lung biopsy in diagnosis of lung lesions in
      hemoblastosis (HB) patients. MATERIAL AND METHODS: The results of diagnostic
      biopsies of the lungs obtained from 22 HB patients are presented. Ten patients
      had no respiratory insufficiency (RI), twelve patients had RI. The biopsy was
      transbronchial in 1 case, thoracoscopic in 10 and open in 11 cases. RESULTS: In
      RI-free patients lung biopsy was informative in all the cases. The biopsy
      provided information which allowed therapy modification resulting in improvement
      of the patient condition. In RI patients biopsy was informative in 8 of 12
      patients. Nonspecific changes in the lungs were identified histologically in 2 of
      12 patients. In 2 RI patients lung biopsy confirmed the diagnosis made after
      examination of the bronchoalveolar lavage. Modification of therapy after the
      biopsy was conducted in 58.3% HB patients with RI. Improvement was seen in 2 of
      them. 10 of 12 patients with RI died within 1-2 weeks after biopsy. CONCLUSION:
      Lung biopsy in HB patients should be obtained only after examination with
      noninvasive methods and before development of RI as prognosis after lung biopsy
      in the presence of RI is unfavourable. The histological material should be
      examined for all expected pathogens.

PMID- 14669610
TI  - [Use of xeloda (capecitabine) in the treatment of cancer patients (review)].

PMID- 14669611
TI  - [Multiple molecular-genetic defects in a woman with mixed hyperlipoproteinemia
      and early ischemic heart disease].
AB  - AIM: Analysis of genes of apolipoprotein E (apoE), LDLP receptor and
      methylentetrahydrofolate reductase (MTHFR) in a female patient with mixed
      hyperlipoproteinemia (HLP) and early ischemic heart disease (IHD). MATERIAL AND
      METHODS: A patient with a mixed form of HLP and 5 her relatives were examined
      genetically. The genotype of apoE and MTHFR was determined using a restrictive
      analysis of PCR fragments. Conformation of one chain DNA was used to analyse gene
      of LDLP-receptor with following sequencing of anomalous DNA. RESULTS: The proband
      had changes in all examined genes: nucleotide replacement of A370T gene of LDLP
      receptor, nucleotide replacement of MTHFR gene C677T and epsilon 2/epsilon 2
      genotype of apoE. None of the relatives carried more than one polymorphism by the
      studied genes. CONCLUSION: Early IHD in females can be caused by combination of
      polymorphisms of genes associated with development of atherosclerosis.

PMID- 14669612
TI  - [Relationship between polymorphism of non-coding regions of human mitochondrial
      genome and primary cardiac conduction disorders].
AB  - AIM: Analysis of associations between idiopathic disturbances of cardiac
      conduction (DCC) and polymorphism of mitochondrial genome. MATERIAL AND METHODS:
      A family examination was performed in 431 probands with various DCC and 1347
      relatives of the first, second and third degree of kinship (the study group). All
      the examinees were divided into four subgroups. These included 158 probands with
      atrioventricular block (AVB) of various degree and their 518 relatives (subgroup
      1); 50 probands with a complete right bundle-branch block (BBB) and their 161
      relatives (subgroup 2); 108 probands with a complete left BBB and left anterior
      branch of the His bundle and their 152 relatives (subgroup 3); 115 probands with
      sick sinus syndrome (SSS) and their 327 relatives (subgroup 4). The control group
      consisted of 104 probands without clinical ECG manifestations of cardiac diseases
      and their 321 relatives. All the examinees have undergone ECG, atropin test,
      echocardioscopy, electrophysiological examination of the heart and mitochondrial
      DNA (mDNA). RESULTS: Comparison of the incidence of mDNA D-loop restriction sites
      in the group of patients with idiopathic DCC and controls has found higher
      frequency of the Hae III 16517 site in the group of the patients (p = 0.0480). By
      location of the blocks (atrioventricular and intraventricular), the site occurred
      more frequently in patients with AVB (86.36%). The variant "+" by the site of Hae
      III 16517 mDNA was found to associate with disturbances of cardiac conduction,
      more closely in AVB. CONCLUSION: Variability of mDNA may be an etiological factor
      of idiopathic DCC pathogenesis.

PMID- 14669614
TI  - [Intravenous thrombolytic therapy in myocardial infarction (review)].

PMID- 14669613
TI  - [Genetic determinants of hereditary thrombophilia in pathogenesis of venous
      thrombosis].
AB  - AIM: To study the role of genetic determinants of hereditary thrombophilia in
      pathogenesis of various clinical manifestations of venous thrombosis in the
      citizens of the North-West Region of Russia. MATERIAL AND METHODS: Mutations of
      the genes of factor V (FV Leiden), prothrombin (G20210-A) and polymorphism C677-T
      in the gene of methylentetrahydrofolate reductase (MTHFR) were detected using
      polymerase chain reaction (PCR) with a following restriction analysis of PCR
      product in 183 patients with venous thrombosis (115 with isolated thrombosis of
      the deep veins and 68 with thromboembolism of the pulmonary artery). RESULTS: It
      was established that mutation FV Leiden is a significant risk factor of deep vein
      thrombosis in the legs and postthrombotic disease, but this mutation is weakly
      associated with pulmonary artery thromboembolism (PAT). An essential PAT risk
      factor is carriage of the variant prothrombin G20210A. CONCLUSION: Determination
      of prothrombotic genotypes is a key factor of treatment efficacy and prevention
      of life-threatening thromboembolic complications.

PMID- 14669615
TI  - [Clinical and hemodynamical efficacy of prestarium and its role in the treatment
      of chronic pulmonary heart].
AB  - AIM: To assess clinical efficiency and safety of ACE inhibitor prestarium
      (Servier, France) with specification of its effects on central and pulmonary
      hemodynamics, hepatic blood flow, indications in patients with chronic pulmonary
      heart (CPH). MATERIAL AND METHODS: 42 patients with chronic obstructive
      bronchitis (COB) complicated by CPH entered the trial. The patients were divided
      into two groups. Group 1 (n = 26) received standard therapy plus prestarium (2-4
      mg/day), group 2 (n = 16) received only standard combined therapy. The examinees
      have undergone ultrasonic investigation of the heart and liver in Doppler modes,
      ECG monitoring, examination for external respiration function, lipid peroxidation
      activity, antioxidant blood defense. RESULTS: Group 1 demonstrated earlier
      positive response. It was found that improvement in functional class of cardiac
      failure induced by prestarium and less frequent episodes of arrhythmia directly
      correlated. Positive changes were stated in central and hepatic hemodynamics,
      systolic pressure in the pulmonary artery lowered more significantly than in the
      control group. CONCLUSION: If COB patients have symptoms of right ventricular
      failure, they are recommended to take prestarium in a daily dose 0.004 g for 4
      weeks to improve intracardiac and hepatic hemodynamics, reduce systolic pressure
      in the pulmonary artery and number of prognostically unfavourable arrhythmic
      episodes.

PMID- 14669616
TI  - [Computer based teaching of diagnostic skills (as illustrated by diagnosis of
      pulmonary artery thromboembolism].
AB  - AIM: To elaborate an innovating computer learning system allowing experienced
      doctors to share their knowledge with beginning physicians; to apply a computer
      expert system in teaching interns to detect pulmonary artery thromboembolism
      (PAT) with emphasis on PAT risk factors and symptoms, on fixation of diagnostic
      skills. MATERIAL AND METHODS: The latest achievements in the field of artificial
      intellect served the basis for design of OSTELA educational computer system which
      operates with decisive rules of a highly skilled cardiologist. In this system
      interns study PAT diagnosis without a direct contact of the teacher with a
      learner. The computer system and its operation are described. RESULTS: Skills of
      PAT diagnosis were taught to 48 interns. The number of correct answers to the
      control test increased by 30%, on the average. CONCLUSION: The proposed computer
      learning system OSTELA was successfully tried in clinics (pilot trials) and is
      recommended for postgraduate education of physicians.

PMID- 14669617
TI  - [The test for nitric oxide metabolites in exhaled air condensate as a method of
      assessing NO-reactivity of the airways in patients with bronchial asthma].
AB  - AIM: To estimate airways NO-reactivity in response to their stimulation with
      fenoterol in different clinical forms of bronchial asthma (BA). MATERIAL AND
      METHODS: The study included 73 patients with BA: mild disease was in 21, moderate
      -in 24 and severe--in 28 patients. Severe BA patients were divided into two
      subgroups: with a stable course (n = 15) and unstable course (n = 13). NO
      producing function of the airways was estimated by concentration of stable NO
      metabolites (mNO)(NO2, NO3) in exhaled air condensate. RESULTS: Spontaneous NO
      producing activity of the airways increases and reaches maximum in severe
      unstable asthma. Fenoterol-stimulated NO-production was minimal in mild BA while
      the most significant augmentation of mNO was observed in unstable BA. Basal level
      of mNO and velocity parameters of external respiration function correlated.
      CONCLUSION: Estimation of NO-reactivity of the airways in the test with fenoterol
      with calculation of the index of airways NO-reactivity provides additional
      information about respiratory system condition in BA patients which may be used
      in clinical pulmonology.

PMID- 14669618
TI  - [A case of Zivert-Kartagener syndrome].

PMID- 14669619
TI  - [Tuberculosis control in the North-West of Russia].
AB  - The basic epidemiological parameters (prevalence, incidence, mortality due to
      tuberculosis) and inadequate efficiency of treatment of patients suggest that
      tuberculosis remains to be a serious problem in the North-West of Russia. There
      is differentiation in the prevalence of tuberculous infection that reaches the
      critical values in the Kaliningrad Region. For successful tuberculosis control in
      the North-Western Region, it is necessary to solve personnel problems, to improve
      methods for early detection of tuberculosis, to enhance the quality of
      therapeutic measures by actively introducing the developed technologies for
      treating drug-resistant pulmonary tuberculosis and for adequately applying
      surgical treatments for tuberculosis at different sites, to set up a tuberculosis
      monitoring system with proper financing all implemented antituberculous measures.

PMID- 14669620
TI  - [Combined therapy of pulmonary tuberculosis by using recombinant interleukins].
AB  - The use of roncoleukin in the combined therapy in patients with pulmonary
      tuberculosis caused by drug-resistant Mycobacterium tuberculosis (MBT) led to
      better immunological parameters and therapeutic efficiency: by month 3 of
      therapy, there was abacillation (69.2% versus 33.3% in the control) (p < 0.05),
      decay cavities closed by months 6 to 7 (59.0% versus 23.1%). The immunotropic
      effect of betaleukin on chemotherapy promoted accelerated involution of a
      specific process with the least pronounced residual changes in the lung tissue;
      by the end of an inpatient stage of therapy, the proportion of patients with
      minor residual changes (Type I and Type II) was 72.5% in the experimental group
      versus 36.8% in the control one (p < 0.05).

PMID- 14669621
TI  - [Pulmonary tuberculosis caused by Mycobacterium tuberculosis of different
      genotypes].
AB  - A relationship of the clinical picture of destructive pulmonary tuberculosis to
      the genotype, drug resistance, and virulence of Mycobacterium tuberculosis (MBT)
      strains was studied. As compared with the processes induced by individual
      genotypes, pulmonary tuberculosis caused by MBT from the family Beijing was found
      to be characterized by more marked clinical symptoms, multisegmental lung tissue
      lesions with multiple decay cavities, by low bacteriostatic blood activity,
      abundant bacterial isolation, and progression. MBT of the Beijing genotype were
      characterized by higher rates of resistance to antituberculous drugs and their
      combinations than were the strains of individual genotypes; they have a high
      virulence, which is likely to enhance their transmissibility and to determine the
      poor course of a specific process.

PMID- 14669622
TI  - [Active bronchial tuberculosis in respiratory tuberculosis].
AB  - A total of 1212 patients aged 1.5 to 70 years were examined in 1998 to 2001.
      Children under 6 years of age underwent bronchoscopy (BS) using a rigid
      bronchoscope under anesthesia; the remaining had fibrobrochoscopy by sampling
      with conventional methods. Active bronchial tuberculosis (ABT) was detected in 74
      (6.1%) of the 1212 patients. There was a rise in the incidence of ABT from 4.0 to
      9.4%; from 4.3 to 10.9% in secondary pulmonary tuberculosis and from 4.2 to 11.2%
      in primary one. In patients with secondary pulmonary tuberculosis, ABT was more
      frequently encountered in infiltrative (7.8%) and fibrocavernous (6.2%) pulmonary
      tuberculosis. A more severe course of ABT was seen in intrathoracic lymph nodal
      and fibrocavernous pulmonary tuberculosis with a predominance of fistular (19.2%)
      and ulcerative (46.6%) forms of ABT.

PMID- 14669623
TI  - [Evaluation of the functional activity of the bronchial mucosa in pulmonary
      tuberculosis and other lung diseases].
AB  - Tracheobronchography using tantal powder was used to study the functional
      activity of the intact and altered bronchial mucosa that manifested itself as the
      unchanged outline of the mucosa and its clearance (mucociliary clearance). With
      the intact mucosa, the sequence of its clearance was established; the mechanism
      of powder transport was studied, which showed up as the appearance of metachronal
      fields, fusion of particles into conglomerates that form currents that direct
      towards the larynx. The clearance of the mucosa was over by hours 20-24. With the
      altered mucosa (tuberculosis and other diseases), the sequence and mechanism of
      its clearance were impaired. The outline of the mucosa was chaotic; there was a
      long powder retention (48-72-hour or more) in cancer and bronchoectases. There
      was retrograde transport of particles into the minor bronchi. The found
      differences in the activity of the mucosa in pulmonary tuberculosis and lung
      cancer allow this method to be used for differential diagnosis.

PMID- 14669624
TI  - [Outcomes of local interventions into the caverns in patients with destructive
      forms of postoperative recurrences of pulmonary tuberculosis].
AB  - The paper presents the outcomes of 48 cavernoplasties for destructive forms of
      postoperative recurrences, which was 23.5% in the structure of all interventions
      for postoperative recurrences. One-stage cavernoplasty was performed in 17
      patients; 31 patients underwent multistage cavernoplasty (with a period of open
      sanitation). After one-stage cavernoplasty, at discharge 2 (11.8%) of the
      patients were found to have formed residual caverns due to detachment of a muscle
      flap, other complications were not recorded in this group of patients. After
      multistage cavernoplasty, the above complications developed in 5 (16.1%) cases.
      There were deaths after these operations. In the late postoperative periods, a
      steady-state abatement of the process occurred in 12 (33.3%) patients, a relative
      stable course of tuberculosis with mild exacerbations was noted in 8 (22.2%)
      patients; further progression was revealed in 44.4% of the cases; late
      postoperative mortality was 27.8%.

PMID- 14669625
TI  - [Peptic ulcer is a risk factor in the surgical treatment of pulmonary
      tuberculosis].
AB  - Peptic ulcer of the stomach and duodenum is the most common (10-18%) concomitant
      gastrointestinal pathology in phthisiosurgical patients. Treatment of these
      patients presents a challenge due to a drastic reduction in the efficiency of
      oral antibacterial therapy resulted from poor tolerability of chemical drugs and
      to a risk for surgical complications particularly in the early period after lung
      surgery. In 1996-2002, a total of 495 patients with tuberculosis at various sites
      were endoscopically studied; peptic ulcer in different phases was detected in
      30.9% of the patients. There has been a considerable increase in the incidence of
      peptic ulcer among phthisiosurgical patients in the past 3 years (up to 16-17%
      among those undergone lung surgery for tuberculosis). A package of measures has
      been developed to reduce the incidence of life-threatening complications due to
      peptic ulcer in the postoperative period. It is concluded that peptic ulcer is a
      significant risk factor in phthisiosurgery as a serious contraindication to
      planned surgery and as a source of postoperative complications.

PMID- 14669626
TI  - [Neutrophilic and lymphocytic factors of an immune response in renal
      tuberculosis].
AB  - Fifty-eight patients with nephrotuberculosis at its peak were found to have a
      high functional activity of neutrophilic granulocytes, as determined by the
      lysosomal cation test, by the levels of myeloperoxidase and lactoferrin. The
      subpopulation of lymphocytes, concentrations of tumor necrosis factor-alpha (TNF
      alpha), interleukin-2 (IL-2), as well as those of IL-2 in a combination with its
      soluble receptor (SR-2) in the serum and supernatant of cellular cultures
      stimulated by phytohemagglutitin and PPD were studied. The findings suggest that
      there is a close correlation between the high concentrations of IL-2 and PP-alpha
      and the decreased content of activated lymphocytes expressing receptors to IL-2
      (CD25+). Clinical remission has been ascertained to be attended only by a partial
      normalization of immunological parameters with antituberculous therapy.

PMID- 14669627
TI  - [Instrumental correction of severe kyphosis in tuberculous spondylitis in young
      children (new technology)].
AB  - A new mode has been proposed to correct deformities in tuberculous spondylitis
      complicated by more than 50 degrees kyphotic deformity. The mode involves
      extended repair of the vertebral column, supplemented by the use of Luque
      modified posterior multisupport hooked contractors. The mode ensures correction
      deformity to 47 degrees. The procedures of a surgical intervention are described.

PMID- 14669628
TI  - [Clinical and laboratory features in tuberculosis and osteomyelitis of the
      spine].
AB  - Tuberculous spondylitis runs atypically with its acute onset, high fever, and
      violent pain in 20% of cases. This disease is characterized by a high specific
      activity of T lymphocytes, by high levels of antituberculous antibodies, by a
      higher activity of adenosine deaminase, by higher concentrations of IgA and IgE.
      The gradual onset and few-symptom course of hematogenous osteomyelitis were
      revealed in 15% of cases. In osteomyelitis, there was a low concentration of
      antituberculous antibodies, higher levels of low and medium molecular mass, and
      IgG.

PMID- 14669629
TI  - [Use of carbon-carbonic implants in surgery of tuberculous spondylitis].
AB  - For surgical treatment of spinal tuberculosis, carbon-carbonic implants were used
      for anterior spondylosis in 29 patients; in 14 of them bone autografts were
      additionally applied. Carbon-carbonic implants reliably fixed the operated part
      of the vertebral column, prevented an increase in kyphotic deformity, and, in
      combined plastic repair, created favorable conditions for consolidation of bone
      autografts. A bone-carbon block formed in the late postoperative period.

PMID- 14669630
TI  - [Active genital tuberculosis with peritoneal involvement in women].
AB  - The paper presents the results of a study of clinical and laboratory features in
      patients with active genital tuberculosis with peritoneal involvement. It has
      been shown that patients with active genital tuberculosis involving the
      peritoneum show a more pronounced clinical picture and changes recorded by
      laboratory studies than those with a restrictive process. A growth of the number
      of patients with specific peritonitis, an unwarranted increase in the volume of
      surgical interventions, lack of systemic data on this category of patients under
      the present condition make it necessary to make further studies of this problem.

PMID- 14669631
TI  - [Microbiological and molecular genetic characterization of Mycobacterium
      tuberculosis strains isolated from patients with multiorgan and generalized
      tuberculosis].
AB  - The paper presents the microbiological and molecular genetic characteristics of
      Mycobacterium tuberculosis (MBT) isolated from multiple lesion foci in 26
      patients with multiorgan and generalized tuberculosis. Cultures of MBT of the
      family Beijing were isolated from the pathological specimens taken from 17
      (65.4%) patients; those with individual genotypes were in 9 (34.6%) patients. The
      study indicated that cultured MBT from different types of pathological material
      from 25 of the 26 patients had identical spoligotypes irrespective of their
      clinical diagnosis. At the same time minor profile IS6110 changes might occur in
      the Mycobacteria of a patient during persistence. It may be concluded that
      multiple foci of tuberculous affliction in the patients are of unique origin and
      have the mechanism of development, associated with endogenous reactivation of
      infection.

PMID- 14669632
TI  - [Some aspects of determination of the sensitivity of Mycobacterium tuberculosis
      to ethambutol using a semiliquid medium].
AB  - In addition to the earlier developed rapid technique for determining the drug
      resistance of Mycobacterium tuberculosis (MBT) to essential antituberculous drugs
      by using semiliquid medium (SLM), the author proposes a procedure for determining
      their resistance to ethambutol. She shows it necessary to use the drug only as a
      powder. The mean minimum suppressing concentrations of ethambutol in the
      semiliquid medium have been determined for stock cultures, sensitive and
      resistant strains, which are 3.5 +/- 2.5, 4.5 +/- 1.4, 8.5 +/- 1.6 micrograms/ml.
      Parallel determination of the sensitivity of 91 MBT strains by using the standard
      Lowenstein-Jensen medium and SLM has yielded the optimum concentration of
      ethambutol (5 micrograms/ml), which is marked by the highest (84.4%) percent of
      coincidence of results.

PMID- 14669633
TI  - [Parameters of acquired immunity and cation proteins of neutrophilic granulocytes
      in pulmonary tuberculosis].
AB  - Clinical and immunological studies of 61 patients with pulmonary tuberculosis
      have indicated that the status of acquired and congenital (natural) immunity
      assessed by the intra- and extracellular levels of cation proteins of
      neutrophilic granulocytes is different in different clinical forms of pulmonary
      tuberculosis. The found correlations suggest that there is a relationship between
      the factors of acquired and congenital immunity and that cytokines are involved
      in the regulation of specific inflammation. More active degranulation of
      azurophilic granules of neutrophils occurs due to myeloperoxidase. Unlike other
      forms, fibrocavernous pulmonary tuberculosis shows a negative correlation between
      intra- and extracellular content of cation proteins. The findings make it
      possible to use the parameters of congenital immunity for more detailed
      characterization of an immune response in tuberculosis, which may be essential in
      developing new pathogenetic therapy regimens.

PMID- 14669634
TI  - [Activating effect of bestim on the macrophages in experimental tuberculosis of
      varying severity].
AB  - The synthetic dipeptide bestim was tested for effects on the functional activity
      of peritoneal macrophages on 400 non-inbred albino mice while simulating
      generalized tuberculosis of varying severity (classical, acutely progressive, and
      slowly progressive). Bestim was shown to have a stimulating effect on the
      activity of macrophageal phagocytosis of yeast cell suspension. The agent was
      also found to exert a restorative effect on the absorptive and digestive
      functions of macrophages during their inhibition during infection and under the
      influence of long-term (more than a month) etiotropic therapy. Bestim showed an
      activating effect on the content of extracellular 5-nucleotidase during the
      classical and acutely progressive course of infection. It was shown to have a
      modulating effect on the macrophageal generation of superoxide radicals, by
      enhancing the inhibited HCT activity in acutely progressive infection and by
      reducing the elevated level of superoxide production in slowly progressive
      tuberculosis. In slowly progressive tuberculosis, the drug produced a stimulating
      effect on the adhesive activity of macrophages.

PMID- 14669635
TI  - [History of St. Petersburg Research Institute of Phthisiopulmonology, Ministry of
      Health of Russia].

PMID- 14669636
TI  - [Circular resection of the upper trachea for concomitant postintubation
      cicatricial stenosis and mycobacterial lesion].

PMID- 14669637
TI  - [The White Paper of the health professions of Catalonia].
AB  - The White Paper of the Health Professions of Catalonia (WPHPC) is a strategic
      document for the development of the health professions. It deals with the main
      components of the manpower development (education, management and planning) in
      relation to the health services development required to attain the objectives
      defined in the Catalan Health Plan. The WPHPC fosters the coherence between
      social needs and professional competencies required to respond to them, as well
      as to the quantitative aspects of service needs under adequate standards of
      quality, effectiveness and efficiency. The WPHPC has followed a methodological
      process with maximum stakeholder participation and transparency. Citizens,
      professionals and health organizations have contributed significantly. The
      conclusions and recommendations of the WPHPC are organized around four axis: the
      citizenship, the professionals, the health care organizations and the health care
      model. Key elements are: the requirement of a new social contract between the
      different stakeholders, the values of professionalism, the need for a new
      credentialism of professional competencies, innovation in the education process,
      innovation of governance and management for organization of knowledge, the
      redistribution of work inside teams requires deregulation and reregulation of the
      professions, the need for actualized data on workforce and job positions and the
      permanent requirement of sociological research.

PMID- 14669638
TI  - [Policy and management of human resources in the health care system of Portugal].
AB  - Portugal has adopted the Beveridgian model of National Health Service after the
      revolution of 1974. However, certain principles have been proclaimed long before
      that date. In particular, equity in access to and solidarity in financing of
      health care have been emphasized since many decades, although not yet completely
      implemented nowadays. The NHS is managed by the Ministry of Health who employed
      in 1999 approximatively 115,500 professionals. In 1998, the Portuguese NHS had
      245 medical doctors and 334 nurses per 100,000 population. As concerns ambulatory
      care, the NHS deploys throughout the country health centers where GPs act as
      gatekeepers. The NHS is plagued by several chronic shortcomings: politics and
      politicians are deeply involved in its decision-making process, its information
      system is weak, manpower planning is lacking, the medical careers outside
      hospitals are not appreciated, continuing education of health workers is
      neglected, the working conditions and skill-mix are deteriorating and, finally,
      the remuneration system is outdated.

PMID- 14669639
TI  - [The physician/population ratio in Switzerland: the impact of its regional
      variation on mortality, health expenditures and user's satisfaction].
AB  - An opinion survey conducted in 1997 in the various Swiss "cantons" produced the
      following findings: 1. The satisfaction of the population concerning the
      provision of ambulatory care does not increase when the physician/population
      ratio increases. It is not clear whether a decrease of "oversupply" gives raise,
      at least in the short term, to a feeling of dissatisfaction. 2. The perception of
      signs of shortened supply does not increase when the physician/population ratio
      decreases. 3. When the cantons are grouped by level of physician/population
      ratio, the different groups show nearly the same health performance as measured
      by the rate of avoidable mortality. 4. The number of consultations per capita
      increases clearly in the "cantons" having high physician/population ratios.
      Increased ratios have clearly an impact on health expenditures.

PMID- 14669640
TI  - [Supply of health care in the Australian bush: human resources and government
      policy].
AB  - The Australian bush--the heart of Australian folklore and a fascinating
      attraction for tourists, whether from within Australia or other countries--does
      not enjoy the same attraction for professionals across a range of industries
      including health, where there is a chronic shortage of human resources. Whilst
      data vary considerably between regions, in many cases, Australians from rural and
      remote regions have a lower health status than the overall population. This is
      particularly true of the population of Indigenous origin. There are about 250
      medical practitioners for 100,000 people in Australia. This number varies between
      about 300 in the capital cities and just over 100 in the remote areas, the latter
      being mostly general practitioners as there are hardly any hospitals and
      specialists in those remote areas. The data change across professions--for
      example the number of nurses is about the same in capital cities and in remote
      areas: about 1000 full time equivalent for 100,000 people. They change too when
      we consider rural regions that are less or not isolated: in some instances, these
      are less supplied than remote areas, where access to care however remains more
      critical because of distance. The demographic profile of the professions examined
      in this paper also vary between regions, giving more urgency to workforce
      planning issues. The Australian government has embarked on the delivery of a
      major rural health strategy aimed at increasing access to health care in the
      rural and remote regions--through the provision of more and better services
      (specialist services; multipurpose centres); attracting more health professionals
      (scholarships for health students; setting up of rural universities); and
      retaining and supporting those professionals in rural and remote areas (on-going
      training; support programs for families and overseas trained doctors; practice
      management and financial incentives).

PMID- 14669641
TI  - [Numbers of doctors and medical training:the situation in a medical school in
      Algeria].
AB  - In 1962, at the Independence, there were in Algeria about 500 medical doctors to
      take care of a population of 10 million. The situation has slowly improved later
      on. Nowadays, there are 45,000 medical doctors in the country (26,700 in the
      public sector and 18,300 in the private sector) i.e. more than 1 medical doctor
      per 1,000 population. However, the improvement has been more apparent than
      effective. The geographic distribution of physicians evidences a profound
      shortage in the rural areas and small cities. An opinion survey conducted on the
      medical students at the medical school of Oran shows a deep gap between the
      contents of their training and the real needs of the population.

PMID- 14669642
TI  - [The World Health Organization and the development of human resources of the
      health system].
AB  - Health workforce is among the main components of the health care system. The
      performance of the latter depends on the knowledge, competence and motivations of
      the various categories of health workers. The task of the World Health
      Organization is to analyze the main problems related to health workforce and to
      help member-states overcome these problems. An other task is to facilitate
      intercountry comparisons. To attain these objectives, WHO has developed a
      conceptual framework, taking into account elements such as the labour market, the
      health care system, the policies and macro-factors (economic, socio-demographic).
      Among the main issues related today to health workforce, one can quote: the
      numbers and distribution of health workers, their migration, their involvement
      into the field of public health, the contents of their training, and, finally,
      the increased risk factors they are challenging.

PMID- 14669643
TI  - [Inventory of the main factors determining the attraction, installation and
      retention of physicians in remote areas].
AB  - A literature search (restricted to Australia, Canada and the USA) finds out 37
      papers dealing with the topic. The factors are grouped into 3 areas: personal,
      occupational and environmental. In each area, the search tries to identify the
      determinants of attraction, of installation and of retention. However, more works
      are needed to better understand how these factors interact at the various stages
      (attraction, installation, retention) of the decision-making process of a medical
      doctor. Undoubtedly, the weight of each factor varies when the health system
      undergoes profound changes (e.g. drastic increase of the female doctors within
      the profession) or when the society itself changes its values regarding work,
      family, leisure....

PMID- 14669644
TI  - [Governmental measures in Quebec to promote medical practice in remote or
      isolated areas].
AB  - In the Province of Quebec a list of areas designated "remote" and "isolated" is
      published by the government. The list is revised yearly. The physicians who set
      up their office in these areas are entitled to receive financial and non
      financial supports from the government. The list of these supports has expanded
      broadly during the last 2 decades. Moreover, the government has designed a number
      of measures aimed at young medical students to attract them to these areas after
      they are graduated. Certain internal reports in the Ministry of Health and some
      publications have tried to assess the effects of all these governmental efforts.
      But an exhaustive appraisal is not yet available.

PMID- 14669645
TI  - [German experience of planning medical installations].
AB  - Since the 19th century, Germany has adopted the Bismarckian model: the medical
      doctors in private practice provide ambulatory care to the insured people (nearly
      all the population) and are paid by (public) insurers on a fee-for-service basis.
      The country introduced in 1993 a large-scale reform composed of several steps:
      (i) delimitation of geographic areas having similar characteristics; (ii)
      calculation for each area various physician/population ratios, each related to a
      specialty; (iii) if the ratio of a specialty in an area exceeds the average
      national ratio (of the specialty) by 10% or more, the doctors of the specialty
      are not allowed to set up their office in the area; (iv) if the ratio of a
      specialty in an area is lower than the average national ratio by 10% the area is
      "open". After a decade, one can say that the reform has succeeded in curbing the
      growth in the numbers of medical doctors. Today, there is nearly no possibility
      for a medical specialist to set up a private office, unless he/she accepts to
      practice as GPs or to succeed to an other colleague of his specialty. As a matter
      of fact, many areas are still open to GPs. The medical profession is aging and
      the young graduates are not motivated to set up office. The country may possibly
      go down from oversupply in the 80's to medical manpower shortage in the next
      decade.

PMID- 14669646
TI  - [Routine examination of cervical spinal cord and spinal column during forensic
      autopsies].
AB  - Examination of the cervical spinal cord is a rare additional autopsy technique
      applied in forensic autopsies. Injuries of the neck region are fatal in a
      considerable number of cases. However, such technique is neglected especially
      while a different cause of death is found. Research on 316 autopsy cases (about
      10% of all cases during that time) was undertaken. Groups of "possible trauma"
      (gross anatomy and microscopic examination of the cervical spinal cord) and
      "possible non-trauma" (gross anatomy examination) cases were investigated. There
      were 68 gross anatomy and 61 microscopic (blood suffusions) "positive" findings.
      There were about 40% gross anatomy and about 46% microscopic (blood suffusions)
      changes giving evidence of trauma of that region in groups of victims of traffic
      accidents. Techniques of examination of the cervical spinal cord and spinal
      column with the addition of microscopy in selected cases can prove the cause and
      mechanism of death. While neglected, especially in obscure autopsy cases, could
      give the reason that possible medical malpractice occurred.

PMID- 14669647
TI  - [Cardiomyocyte apoptosis in immunohistochemical diagnosis of sudden cardiac
      death].
AB  - In a considerable number of cases of sudden death "routine" diagnosis is
      insufficient to prove myocardial ischaemia especially in early myocardial
      infarction. One of the additional methods of postmortem diagnosis is detection of
      cardiomyocyte DNA fragmentation related to apoptosis. The authors presented
      research on 34 cases. All postmortem examination were conducted in the Chair of
      Forensic Medicine of the Jagiellonian University in Krakow. The data from history
      were taken into account as well as the results of gross macroscopic and
      microscopic examination (hematoxylin et eosin staining). In 19 cases the result
      of TUNEL assay was positive, in 5 apoptotic cell count was 80-90%. "Positive"
      cases showed focal or diffuse apoptotic myocytes. In 15 cases apoptotic reaction
      was negative including 3 cases of fatal ethanol intoxication and 1
      aminotryptyline intoxication. In 22 cases the acid fuchsin technique (Nielsen's)
      was applied. The authors confronted their results with the data from literature
      and presented principles of qualification and practical interpretation of
      immunohistochemical apoptosis reaction.

PMID- 14669648
TI  - [Chest stab wound comparison in suicidal and homicidal cases].
AB  - In view of the appearance of cases of homicides by stabbing in which the killer
      claims that the victim committed suicide cases of homicides and suicides of this
      type have been compared. Contrary to the opinions appearing in the medico-legal
      issues stating that the commonly described features of the suicidal wounds such
      as tentative wounds, stabbing in the intercostals space, "removal" of clothes do
      not appear in some of the suicides, a few of these features do appear in each of
      the examined cases. Having considered the horizontal wound arrangement in the
      skin, which is a newly described feature, the differentiation between homicides
      and suicides are more categorical. In addition to that, the low level of alcohol
      in the blood is an extremely characteristic feature of the suicide by chest
      stabbing. On the contrary, typical features of suicidal death don't appear in
      cases of "aggressive self-destruction", self inflicted fatal wounds inflicted by
      a person with mental disorders.

PMID- 14669649
TI  - [Population genetics of the D1S80 system in a Central Poland region].
AB  - Population data concerning the D1S80 system based on the analysis of 775 persons
      from Central Poland region was presented. Accordance with the Hardy and Weinberg
      equilibrium (HWE) was proved using two different statistical approaches. The
      parameters for the appropriateness of this marker for investigations in the
      analysed population was also assessed: heterozygosity--0.79, PIC--0.77, PD--0.93,
      PE--0.62, PI--12.8 and frequency of mutation events--0.27%.

PMID- 14669650
TI  - [Significance of chromatographic methods coupled with mass spectrometry for
      identification of drugs for medico-legal purposes exemplified by
      chlorphenoxamine].
AB  - This work presented the death of the 17-year old women M.F. The direct cause of
      death was violent strangulation. Toxicological investigation made possible a
      wider explanation of the case, since M.F. was under influence of associative
      action of diphenhydramine and ethanol which could not avoid having an influence
      on the tragic events accompanying the death. Besides a comprehensive
      interpretation of the toxicological results in medico--legal aspect large
      methodic documentation has been presented which proves the usefulness of
      chromatographic methods coupled with spectrometry for identification of
      xenobiotics found.

PMID- 14669651
TI  - [Cocaine toxicity].
AB  - The paper presented the effects of cocaine on the human, particularly toxic
      effects induced by chronic use of cocaine. It was demonstrated that the toxic
      effects depend on the mode of administration (oral, nasal, intravenous, inhaled)
      of various forms of cocaine (cocaine hydrochloride and cocaine base, i.e. crack).

PMID- 14669652
TI  - [Sobriety testing in case of lack of cooperation of the examined person--the
      legal basis of the physician's activities].
AB  - The legal aspect of blood sample taking for alcohol concentration from
      suspicious, uncooperative persons is described in this paper. The Polish law
      allows for a possibility to take blood samples for alcohol concentration from
      suspects only by a physician or another skilled medical worker and only when
      consent is given to the medical procedure. The traffic act makes an exception for
      cases when the suspects are drivers and the suspicion concerns driving under the
      influence of alcohol. Taking blood samples is the medical worker' obligation in
      accordance with the law. The physician can refuse to do this only when the
      procedure threatens the life or health of the suspect.

PMID- 14669653
TI  - [New Polish regulations regarding accidents in the workplace].
AB  - With the new year 2003 the new Polish "Law on Social Security Insurance in case
      of Workplace Accidents and Occupational Illness" came into force, which annulled
      the previous "Law on Benefits in case of Workplace Accidents and Occupational
      Illness", dating from 1975, together with its executive provisions, which
      contained as an Appendix a table for determining the percentage of health loss in
      a given case. This article, comparing the previous and current laws, analyzes
      their influence on the process of delivering certificates in legal medicine. In
      the area of direct interest to the legal medicine practitioner there is
      practically no difference caused by the introduction of the new law, but because
      of the lack of executive provisions to the new law, the former directive
      concerning the principles and mode of issuance of loss-of-health certification,
      including the health loss percentage table, will continue to be applied.

PMID- 14669654
TI  - [The case of a collar-bone wedge-fracture caused by the impact of safety-belt
      clasp].
AB  - In this study the case of a collar--bone wedge--fracture caused by the impact of
      safety--belt clasp was described. The presence of wedge--fracture is proof of an
      active mechanism of injury. This kind of fracture was described in traffic
      accidents as a Messerer fracture so far. The case of a wedge--fracture of the
      ulnar caused by impact of a baseball bat was also described. This study proves
      that Messerer fractures of bones are not characteristic only for long bones but
      may be connected with other types of bones if only the power of impact is strong
      enough to cause excessive bending of the bone trunk.

PMID- 14669655
TI  - [Atypical cases of suicides].
AB  - The authors present two cases stated by the Legal Authorities to be suicides.
      Medicolegal autopsy picture in both was absolutely unusual when comparing with
      these type of cases and suggested death due to crime.

PMID- 14669656
TI  - [Crimes against life in the material of Cracow's Institute of Forensic Medicine-
      comparative analysis in the years 1986-2000 and 1996-2000].
AB  - The authors presented a comparative analysis of crimes against life in five year
      periods of the past and present political systems based on autopsy material of
      Cracow's Institute of Forensic Medicine. Investigation of these types of crime
      confirmed sociological observations of arising the criminal trends in the last
      years. The incident of these types of crimes arose in the last period by about
      40% in a relation of male to female victims 3.7:1. Probable motives of these
      crimes were: drinking 8%, decline in family relationships 12%, fight and revenge
      9% robbery 8%, sexual offenses only in 1%. In 61% of analyzed cases the motives
      were unknown. Among the weapons of crime the most often used were blunt objects
      and death due to stabbings and cuts. A very high incidence of fire arm crimes in
      comparison to previous period was observed--from 2 cases in 1986-1990 to 25 in
      the five year period of 1996-2000. 78% of victims were in a state of insobriety
      at the moment of crime.

PMID- 14669657
TI  - [Importance of comparative odontological research in the whole entirety of
      identification proceedings on the base of the skull]].
AB  - The complex comparative identification studies based on skull analysis include a
      number of detailed tests of anatomy, anthropology, odontology and surgery. The
      range of tests performed depends primarily on the type of collected comparative
      material. In the paper, particular attention has been devoted to one of the
      stages of the identification procedure, i.e. to comparative odontological tests.
      An attempt has been made to underline their importance in the set of complex
      identification studies, based on the skull, and to accentuate the importance of
      appropriate and very accurate dental records for the forensic-medical
      applications.

PMID- 14669658
TI  - [Fatal suicidal poisoning using chemicals and drugs in the Jagiellonian
      University Institute of Forensic Medicine, in the years 1991-2000].
AB  - 191 cases of fatal suicidal poisonings in the years 1991-2000 were analysed.
      Postmortem examinations were conducted in the Institute of Forensic Medicine of
      the Jagiellonian University. The group of poisonings was selected from a total of
      1937 fatal suicidal cases examined in our Institute. Frequency of suicidal
      attempts, kind of chemicals/drugs used, age and sex relationships, probable
      motives and seasonal a variables were taken into account in our investigation.
      The results were compared to previous studies. Poisonings comprise about 10% of
      the total number of suicidal cases. The most frequent are poisonings using drugs,
      then using chemicals. The number of cases of males committing suicide by
      poisoning is about twice as many as seen in females in such cases. The most
      important motives were mental disturbances, the latter most frequent motives were
      alcoholism and somatic illnesses. The peak of number of cases was noted in the
      summer months, June and July (about 1/3 of the total number of cases). In the
      last decade we systematically observed both a rise in the total number of
      suicides and a lower percentage of poisonings.

PMID- 14669659
TI  - [Iatrogenic injury of the trachea--a case report].
AB  - The case of iatrogenic trachea injury during endotracheal intubation is reported
      in this article. The case concerns a 36 years old woman, with diagnosed DIC
      resulting from postpartum complications. Injury of the brachiocephalic trunk and
      the tracheoarterial fistula were found during autopsy. The authors considered the
      time and the mechanism of both injuries.

PMID- 14669660
TI  - [Suicide by propane-butane inhalation: a case report and literature review].
AB  - A case of suicide of a 26-year old woman by propane-butane inhalation is
      presented with a description of the circumstances, postmortem pathomorphological
      and toxicological findings. The literature relating to deaths due to inhalation
      of these gaseous substances was briefly reviewed.

PMID- 14669661
TI  - [Conference report on "Aspects of DNA testing used in court," Cracow, November
      16, 2001].

PMID- 14669662
TI  - [Conference report: "Different opinions of the Institutes of Forensic Medicine
      about the classification of disease stages," Osieczna near Cracow, June 20-21,
      2001].

PMID- 14669663
TI  - [Medical opinion about the adverse effect of laser hair removal--a case report].

PMID- 14669664
TI  - [Situation of Polish forensic medicine in the perspective of the joining European
      Union].

PMID- 14669665
TI  - [Determining in the circumstances of head injuries].
AB  - Due to the common character of head injuries and the risk involved, the
      litigation offices are often interested in reconstructing the circumstances of
      such injuries (their number, localization, time, differentiating active and
      passive traumas). The paper presents the possibilities and limitations of the
      methods evaluating the circumstances of head injuries used so far and the chances
      created by new techniques of computer imaging of head soft tissue structures.
      Moreover, the author discusses the evident value of external injuries to the
      head, various cranial fractures (in relation to deducing on the basis of single
      fractures) and foci of brain contusion. The usefulness of modern imaging methods
      (CT and MR) demonstrating the extracranial injuries to soft tissues was
      emphasized.

PMID- 14669667
TI  - [Genetic variation at STR-TH01 locus in the South Polish population].
AB  - We report on a rare allelic variant of the TH01 STR locus. Within this commonly
      used tetranucleotide repeat system, we identified and characterized by
      denaturating gel electrophoresis an allele of the size corresponding to 10.3
      repeats, analogous to the most common 9.3 allele. The novel allele segregated
      from a putative father to the child in a paternity case. We discuss the advantage
      of high resolution second generation multiplex systems (SGM) using internal size
      standards during electrophoresis.

PMID- 14669666
TI  - [Use of intraocular fluid in the medico-legal practice in diagnosing fatal
      poisoning with various psychoactive substances].
AB  - In this paper results of the research on the usefulness of toxicological analysis
      relating to narcotics in intraocular fluid have been presented. The examined
      material comprised intraocular fluids and blood samples collected from 332
      deceased suspected of being intoxicated or poisoned with psychoactive agents. The
      cases in which death resulted from injuries and those where an individual took
      drugs before his or her death were also considered. Drug analysis was carried out
      by fluorescence polarization immunoassay (FPIA). In both biological fluids the
      degree of hydratation was determined. Ethyl alcohol, opiates, barbiturates and
      benzodiazepines were found in all the examined cases. In few cases ethanol
      substitutes such as isopropyl alcohol, ethylene glycol and methyl alcohol were
      indicated. Results of the quantitative examinations were divided into sets
      according to the kind of xenobiotic and then on the basics of concentration of
      the substance found in the blood and vitreous body 2 different groups were
      separated in each set. Statistic analysis of the correlations among xenobiotic
      concentrations in both organic fluids was also performed. The obtained findings
      allow to assume that intraocular fluid can be used for toxicological diagnosis of
      poisonings with psycho-active agents. The analytical results for intraocular
      fluid not only confirms the result for blood but also makes it credible. In
      single cases it can be a sufficient basis to determine and recognize psychoactive
      agents in the deceased.

PMID- 14669668
TI  - [Paternity contradiction cases in the practice of Department of Forensic Medicine
      of Silesian Academy of Medicine in years: 1985, 1990, 1995 and 1996-2000].
AB  - Analysis of paternity contradiction has been presented in this paper. The author
      analyses the amounts, methods of examination used in paternity testing and
      results of these opinions. The amount of contradiction trios rises to 20% of the
      total of paternity testing examined in our Department. In 73% of contradiction
      paternity cases the results are negative--a husband is the biological father of
      his wife's child.

PMID- 14669669
TI  - [Thioridazine intoxication of therapeutic error as the cause of death of a three
      year girl].
AB  - Intoxication with drugs and xenobiotics in children, particularly under the age
      of 7 years, represents a serious diagnostic and therapeutic challenge considering
      the relatively immature enzymatic detoxication systems, greater susceptibility to
      organ lesions, easily destabilized homeostasis (including water-electrolyte
      balance) and limited compensatory mechanisms in acidosis or alkalosis. We present
      the case of a 3-year-old girl, who died 30 hours after admission to hospital,
      with suspicion of ingestion of two or three 100-mg tablets of thioridazine. The
      medical documentation and results of autopsy are in favor of acute
      cardiopulmonary failure caused by extensive cerebral and pulmonary edema as a
      complication of "water poisoning" i.e. acute hypotonic overhydration of the
      child.

PMID- 14669670
TI  - ["Short-lived disease that is a real life hazard"].
AB  - In passing of judgement for the National Memory Institute, in case of "Cross's
      Defenders", the concept "state of temporary life hazard", mentioned in Polish
      criminal code from 1932 year was discussed.

PMID- 14669671
TI  - [Application of polymorphism of HLA-DR locus in personal identification].
AB  - The aim of this paper was to present the results of investigation of the high
      polymorphic HLA-DR locus by the PCR-SSP method. Genomic DNA was isolated from
      whole blood, tissue samples (muscles and brains). HLA-DR alleles were typed using
      the DYNAL DR "low resolution" SSP kit. PCR products were separated on agarose gel
      with ethidium bromide and estimated in ultraviolet light. Phenotypic and
      genotypical rates of blood and tissues have been analysed. After electrophoresis
      in 228 DNA samples 39 phenotypes and 10 alleles were identified. The most
      frequent phenotypes of the HLA-DR locus were 5/6, 6/6 and 3/5. The high frequency
      of HLA-DR 6, DR 5 and DR 7 alleles have been found. No deviations from the Hardy
      Weinberg equilibrium were observed. The HLA-DR locus has a relatively high
      information content (PIC), power of discrimination (PD) and mean exclusion chance
      (MEC). The molecular PCR-SSP method allows for very rapid and highly
      discriminatory HLA analysis. We found the PCR-SSP technique very useful in
      routine HLA-DR identification.

PMID- 14669672
TI  - [Population genetics of 9 Y-chromosome STR loci w Northern Poland].
AB  - A total of 508 unrelated males from the North Poland population were analyzed for
      9 Y-chromosome STRs (DYS 19, DYS 390, DYS 393, DYS 392, DYS 391, DYS 389I, DYS
      389II and DYS 385I/II) using two multiplex reactions and detection of PCR
      products using capillary electrophoresis. In the analyzed sample 328 different
      haplotypes were identified, among which 264 were unique. It was found that the
      model for a Polish population haplotype (DYS 19*17, DYS 390*25, DYS 393*13, DYS
      392*11, DYS 391*10, DYS 389I*13, DYS 389II*30, DYS 385I/II*10,14) is almost 15
      times more frequent in our population than in a cumulative European one. The
      haplotype diversity/discrimination index calculated for 9 loci is 0.9943. In the
      analysed population sample three mutations were detected in the DYS19
      (duplication) and DYS385I/II loci (triplications).

PMID- 14669673
TI  - [Identification of three rare allele: D21S11*24.2, D7S820*9.1 and HUMFGA*19.2 in
      Polish population].
AB  - This paper presents the identification of three rare alleles: D21S11*24.2,
      D7S820*9.1 and HUMFGA*19.2 not observed previously in a Polish population.
      Allelic variants were identified during routine analysis of more than 1600
      reference samples. DNA extracts were amplified using ProfilerPlus kit or monoplex
      reactions. PCR products were separated using capillary electrophoresis with
      fluorescent detection. Population genetics data of D21S11, D7S820 and HUMFGA loci
      including minimal allele frequencies (pmin) in large population samples from
      Poland are also presented.

PMID- 14669674
TI  - ["Alarm substances" as biological markers indicating emotional state before
      death].
AB  - This scientific project presents the results of preliminary examinations aimed to
      identify alarm pheromones secreted by mammals. Wistar male rats were used for the
      experiment. Animals were treated by aversive sensoric stimuli and fear
      conditioning procedures. The animals' behaviour was registered. Quantitative and
      qualitative analysis of air samples taken from their environment was conducted
      with the use of GC-FID and GC-MSD technics. In the rhinocephalon structures
      (olfactory bulb, olfactory tract) the concentration of glutamate was measured.
      During the progress of the experiment increasing behavioral reactions of anxiety
      were observed in the rats. In their atmosphere organic compounds were identified.
      Some of them can be considered to be alarm substances. In the examined structures
      of the rhinocephalon on increased concentration of glutamate in each individual
      was revealed.

PMID- 14669675
TI  - [Use of morphologic changes in the pubic symphysis for age determination in the
      Polish male population].
AB  - The aim of this study was to determine if the Suchey-Brooks age at death
      estimation method could be applied to a male sample from the Polish population.
      Public symphyses were taken from cadavers of 83 males of age 13-88 years. On the
      base of the morphological key features every symphysis was qualified to the
      appropriate age phase. The estimation of means and standard deviations of
      chronological age of every phase was the next step in the study. The differences
      turned out to be insignificant for phases I-III and significant for phases IV-VI.
      These results suggests using the Suchey method only for age estimation of younger
      males.

PMID- 14669676
TI  - [Entomological methods of determining time of death].
AB  - The paper contains descriptions of the entomological methods which can be used in
      determining time of death. It based on the knowledge of groups of arthropods
      (waves of succession), characteristic for stages of decomposition of the corpse
      as well as the biology and longevity of development of necrophagous insects.

PMID- 14669677
TI  - [Death from accidental hypothermia. Part I. Principles of physiology of
      thermoregulation, pathophysiology and mechanisms od death from hypothermia].
AB  - Principles of thermoregulation physiology necessary to understand the
      pathophysiology and mechanisms of death from hypothermia are disputed in this
      paper.

PMID- 14669678
TI  - [Death from accidental hypothermia. Part II. An accidental hypothermia death
      diagnosis--usefulness of observed gross and microscopic morphological changes].
AB  - Morphological changes found during post-mortem examination of victim dying from
      accidental hypothermia were collected and disputed in this paper. The practical
      usefulness of these changes in the diagnosis of sudden death was estimated.

PMID- 14669679
TI  - [Issues related to the identification process of catastrophes victims].
AB  - Catastrophes on an international scale with an increasingly pronounced terrorist
      factor (for example, the terrorist attacks in the United States of America on
      September 11, 2001) are occurring with increasing frequency. This fact compels
      the international forensic medical community--especially at the present moment-
      to undertake coordinated and rapid measures in the area, closely related to our
      profession, of issues connected with problems of identifying the victims of
      catastrophes. To date organizational issues have not been harmonized to the
      required at an international level degree. The subject has been raised frequently
      at congresses and symposiums of forensic medicine. The real and present danger of
      catastrophes at a national and regional level demands the adoption of rapid
      organizational activities at these levels too. Because the victims of such
      catastrophes are often of various nationalities, these activities also demand
      urgent organizational harmonization in keeping with established international
      norms. The following article addresses this issue. It contains propositions in
      outline with the aim of presenting them to discussion. These suggestions refer
      solely to organizational activities on the regional, national, and international
      levels, connected with the issue of identification in the broad sense of the
      word.

PMID- 14669680
TI  - [Collecting and rearing necrophagous insects, important in determining date of
      death, base on the entomological method].
AB  - The entomological method of determining date of death is used in police
      investigation more frequently. In order for correct determination of this date,
      the entomologist must correctly collect and rear the necrophagous insects,
      feeding and breeding on the corpse. Therefore, in this paper, methods of
      collecting, rearing and preservation of flies, water insects and beetles are
      described.

PMID- 14669681
TI  - [Phrenology--another point of view].
AB  - The biography of doctor Franz Joseph Gall (1758-1828) and his theory of
      phrenology were outlined highlighting the criminological issues of it. The real
      scientific aspects of his work were pointed out as well as their relation to
      modern investigations of human brain. The unsatisfactory interest of forensic
      community concerning the issue of postmortem research of psychiatric disorders
      relevant to criminology and forensic medicine were also highlighted.

PMID- 14669682
TI  - [Carbamazepine in modern toxicological casuistry at Department of Forensic
      Medicine of Medical University of Gdansk in the years 1996-2001].
AB  - In this paper the authors presented 20 cases of death of individuals diagnosed at
      Department of Forensic Medicine of Medical University of Gdansk in the years 1996
      2001. In all cases carbamazepine was found in post-mortem material collected from
      the deceased during autopsy. 14 deaths resulted from intoxication after overdose
      of drugs for the purpose of committing suicide. In the other cases carbamazepine
      did not have on influence on the cause of death. The subject of the chemo
      toxicological analysis were blood and urine samples and also specimens of the
      stomach with its contents, liver, kidney, brain and lung specimens collected
      during autopsy. TLC, GC-FID, GC-MS, TLC-UV were used as diagnostic tools.
      Determined carbamazepine concentrations fluctuated between 1.5 to 78.6
      micrograms/ml in the blood.

PMID- 14669683
TI  - [Group intoxication with 2-ethoxyethanol as an ethanol substitute].
AB  - In this paper the authors presented the group 2-ethoxyethanol intoxication of 8
      young men aged between 20 to 22. 50-100 ml of pure compound (diluted with water)
      was administrated as a drink. In this paper symptoms of acute intoxication to
      this compound were presented. GC-FID and GC-MS were used as diagnostic tools. The
      obtained results were compared with the data from available literature.

PMID- 14669684
TI  - [Cases of hanging with bound limbs--suicide, homicide or accident].
AB  - In the paper 6 cases of suicidal hanging and 1 case of accidental hanging were
      presented; in each case limbs of the victim were bound. These hangings always
      cause a suspicion of homicide, therefore the forensic specialist should pay
      particular attention to them, especially during the crime scene examination, they
      should also be carefully investigated by police and the public prosecutor's
      office.

PMID- 14669685
TI  - [Effect of ethylene glycol on antioxidative enzymes and lipid peroxidation
      activity in erythrocytes].
AB  - Investigations were aimed at demonstrating changes in the activity of enzymes
      forming an antioxidative barrier and oxidative stress parameters in erythrocytes
      of rats which were administrated ethylene glycol during 4 weeks. Superoxide
      dismutase activity (CuZn-SOD) was evaluated by the Misra and Fridovich method,
      catalase (EC1.11.1.6.) by the Beers and Sizer method and malonyl dialdehyde
      concentration (MDA) with Placer et all were assessed in the obtained material
      through the evaluation of TBARS compounds concentration. In the 4th week of the
      experiment a decrease in catalase (9.3 U/gHb to 5.7 U/gHb) and superoxide
      dismutase (2378 U/gHb to 1759 U/gHb) activity was observed. Malonyl dialdehyde
      concentration increased from the initial 0.14 mumol/gHb to 0.24 mumol/gHb. The
      investigations carried out have demonstrated that long-term intoxication with
      ethylene glycol leads to a constant generation of free radicals (increase of MDA
      concentration) and gradual exhaustion of the antioxidative system.

PMID- 14669686
TI  - [Enforcement of type M 20 cal. 4 mm cartridges].
AB  - The aim of the paper was to investigate and compare the speed and energy of a
      bullet from 4 mm cal. cartridges of central ignition type M20, both original and
      transformed by addition of different kinds of propellants. Original cartridges
      are characterized by an average speed of the bullet of 144 m/s and average energy
      of 4.8 J. After transformation by the addition of on an average 31.3 mg of
      smokeless powder from a cartridge type LR'22, a maximum bullet speed of 299 m/s
      (average) and maximum energy of 21.2 joule (average) were reached. Our test
      showed that shots using transformed ammunition type M 20 cal. 4 mm can be
      dangerous for both health and life. Multiple M20 shot wounds may be very similar
      to single shot wounds caused by a shotshell cartridge fired from a shotgun
      weapon.

PMID- 14669687
TI  - [Medicolegal problems of "dyadic death"].
AB  - The authors present 9 cases of homicide followed by suicide of the perpetrator-
      so called dyadic death from the practice of the Cracow Forensic Medicine Chair.
      The circumstances of the event, medico legal and psychiatric problems were
      discussed in view of the literature. A typical picture of the perpetrator is male
      of the average age 49, killing his spouse or children. The major reasons of
      dyadic death are: breakdown in a relationship, mental and somatic diseases,
      financial stress. Very uncommon in dyadic death are cases of murder of people
      from outside the closest family.

PMID- 14669688
TI  - [Criminalistic and penal problems with "dyadic deaths"].
AB  - This paper is a supplement to the article "Medico legal problems of dyadic death"
      elaborated by the same authors. Recalling the cases presented there. It is also
      an attempt to present the basic criminalistic, penal and definitional problems of
      dyadic death called also postagressional suicide. Criminalistic problems of
      dyadic death were presented in view of widely known "rule of seven golden
      questions"--what?, where?, when?, how?, why?, what method? and who? Criminalistic
      analysis of cases makes some differences in conclusions but it seemed interesting
      to match both--criminalistc and forensic points of views to the presented
      material.

PMID- 14669689
TI  - [Analysis of selected changes in project the penal code].
AB  - In this paper the authors have analysed selected proposals of changes in the
      project of amendments in the penal code. Special attention has been placed on
      problem of the legality of the "comma" in art. 156 of the penal code. In this
      matter also a review of court jurisdiction has been made.

PMID- 14669690
TI  - [Evolution of Supreme Court settlements relating to DNA evidence in paternity
      investigations].
AB  - The evolution of Supreme Court settlements relating to DNA evidence in paternity
      investigations was presented in this paper. It was found that its opinions have
      essentially changed during the last years as follows: 1) superiority of DNA
      evidence over other proof was perceived by the possibility of positive paternity
      confirmation, 2) attention has been turned to advisability of statistical
      analysis and its possible positive influence on emotional ties between parents
      and child, 3) opinion has been expressed about crossing of borders of free
      judicial estimations in cases of questioning DNA expertise, 4) attention has been
      turned to the possibility of utilisation of other tissues than blood or indirect
      genotyping.

PMID- 14669691
TI  - [Criminalistic-identification aspect of image diagnosis of skeleton pathology
      characteristics].
AB  - In this paper the author showed possibilities for adaptation of the most present
      day medical achievements in the field of noninvasive diagnosis of individual
      characteristics of human skeleton pathology--at crime detection and during
      criminalistic identification particularly. The identification value of image
      diagnosis for individual characteristics of the pathologically changed skeleton
      has been exemplified with: X-ray radiography, both conventional and computer
      assisted tomography, scintigraphy, ultrasonography and nuclear magnetic resonance
      tomography. The paper's conclusion is formulating of new definitions for
      identification method of individuals, based on image diagnosis--named
      osteopathoscopy--which can be an alternative method to controversial radiology.

PMID- 14669692
TI  - [Development of the contemporary age at death estimating methods from cranial
      suture closure].
AB  - The paper presents a review of the most important studies on age estimating from
      cranial sutures. The main directions of investigations, the results of population
      studies and research into sex and race impact were presented in a historical
      context. Particular attention was paid to contemporary, advanced methods of age
      estimating from cranial suture closure.

PMID- 14669693
TI  - [Using Lamendin and Meindl-Lovejoy methods for age at death estimation of the
      unknown person].
AB  - The paper presents the precise description of two methods used for age estimation
      on the base of single rooted tooth and cranial suture obliteration. Using the
      methods mentioned above, the age at death of the unknown person was estimated. A
      comparison of the estimated age and chronological age derived after
      identification, showed high usefulness of the mentioned methods.

PMID- 14669694
TI  - [Analytical problems in examination of small amounts of blood samples taken from
      law offenders].
AB  - In the paper there have presented results of the analysis of small blood samples
      taken routinely from 3 cases after car accidents and 1 rapist. Fluorescence
      polarisation immunoassay (FPIA, Abott) was used for screening examinations of
      narcotics from the group of both opium and cocaine alkaloids, barbituric acid and
      benzodiazepine and also drugs from the group of tricyclic antidepressants.
      Confirmation of the obtained results and full identification of the substances
      analysed were carried out by liquid chromatography with mass spectrometry (LC
      MS). In the causes of car accidents components of "compote" were found (poppy
      straw extract) morphine and codeine (1 case), cocaine (1 case) and also tramadol
      and diazepam (1 case) were also found. In the rapist
      methylenedioxymethamphetamine (MDMA) was determined.

PMID- 14669695
TI  - Guidelines for sedation of the critically ill child.

PMID- 14669696
TI  - Community children's nursing services: the need for development.

PMID- 14669697
TI  - The difference between quantitative and qualitative research.

PMID- 14669698
TI  - Temperature measurement: practice guidelines.

PMID- 14669699
TI  - Improving quality in paediatric respiratory disease management.
AB  - Throughout the development, implementation and dissemination of the Paediatric
      Respiratory Newsletter, effective channels of communication between healthcare
      professionals have been established, highlighting the importance of
      collaboration. Promoting education, training, audit and research, the newsletter
      has nurtured both professional and practice development. The work begun during
      this project, and the outcomes it has achieved, have been developed into an ethos
      that recognises effective clinical practice and organisational development as
      central to the delivery of a quality service. This work informs and is informed
      by strategic developments, in particular, research and development, clinical
      audit, quality, practice development and clinical risk, all of which are observed
      to be the key elements of clinical governance. On a personal level, the project
      has provided me with an opportunity to consolidate information, forge links with
      the multidisciplinary team and establish a framework for the development of
      paediatric respiratory services. We hope it will continue to respond to, and be
      influenced by, changing health and social care demands.

PMID- 14669700
TI  - Diabetes management: hospital or home?

PMID- 14669701
TI  - Retained organs: supporting grieving relatives.

PMID- 14669702
TI  - Child protection: defining 'harm'.

PMID- 14669703
TI  - [The brain, a cardiac risk factor?].

PMID- 14669704
TI  - [Pathophysiologic cardiovascular changes in stress and depression].
AB  - Fear, anger, and grief may precipitate myocardial ischemia and infarction. The
      prognosis of patients with inducible ischemia during mental stress is worse than
      in those without inducible ischemia. The sympathetic nervous system plays an
      important role in stress-associated changes in cardiovascular regulation and
      contributes to cardiovascular morbidity and mortality by inducing
      vasoconstriction and tachycardia, as well as arrhythmia. Hostility--previously
      termed type A personality--is often associated with sympathetic hyperreactivity
      to mental stress and carries an increased risk for atherosclerotic vascular
      disease. As endothelial dysfunction is an early manifestation of atherosclerosis,
      the impact of mental stress on endothelial function is also important. Acute
      mental stress induces prolonged endothelial dysfunction in healthy volunteers,
      which is prevented by selective endothelin A receptor antagonism. This represents
      an important link between mental stress and atherosclerotic vascular disease. In
      addition, patients with depression show hypercortisolemia, and changes in
      platelet function leading to a prothrombotic state. These findings help to
      explain the increased cardiovascular risk in patients with depression.

PMID- 14669705
TI  - [Stress, depression and cardiac arrhythmias].
AB  - A relationship between behavioural factors and cardiac arrhythmogenesis in humans
      has been described. Three sets of conditions contribute to the occurrence of
      arrhythmias: myocardial electrical instability, most often due to coronary artery
      disease; an acute triggering event, frequently related to mental stress; and a
      chronic, pervasive, and intense psychological state, often including depression
      and hopelessness. The autonomic nervous system plays an important role in the
      occurrence of cardiac arrhythmias and it is well documented that mood alterations
      as mental stress and depression influence cardiac autonomic balance. There is an
      increasing body of evidence that patients with the greatest changes in cardiac
      neural regulation with decreased parasympathetic tone coupled with increased
      sympathetic activity are at the greatest risk for developing fatal ventricular
      arrhythmias. These patients have a reduced heart rate variability, increased QT
      dispersion and a decreased baroreceptor sensitivity. The influence of stress and
      depression on the autonomic nervous system and the impact on the occurrence of
      both atrial and ventricular arrhythmias is being discussed.

PMID- 14669706
TI  - [Changes in blood coagulation in stress and depression--from evolution to gene
      regulation].
AB  - Mental stress and depression are characterized by a hypercoagulable state, which
      might mediate the increased coronary risk in individuals who feel stressed or
      depressed. Changes in blood coagulation and fibrinolysis with stress and
      depression are largely mediated by the sympathetic nervous system via
      catecholamine and adrenergic receptor activity. Stress might also affect
      coagulation activity via an influence on the regulation of genes coding for
      coagulation and fibrinolysis molecules. There is some evidence that non-selective
      beta-blocking agents decrease hypercoagulability elicited by acute stress. The
      selective serotonin reuptake inhibitors appear to normalize increased platelet
      activity in depression. Prospective studies need to show whether there is an
      association between coagulation abnormalities in stress and depression with hard
      cardiovascular end-points and whether such an association is favorably affected
      by therapeutic interventions (e.g., medication, psychotherapy, stress
      management).

PMID- 14669707
TI  - [Work, stress and cardiovascular diseases].
AB  - Classical risk factors such as smoking, hypertension or elevated plasma levels of
      cholesterol account only for part of the variance in the probability of
      cardiovascular disease. Work related psychosocial factors such as high job
      demands, low decision latitude or lack of social support often pertain during
      extended periods. Such work related stressors may modulate biological risk
      factors (e.g. by increasing the risk of hypertension) or may elicit adverse
      health behaviour (increased tobacco consumption). Several longitudinal cohort
      studies indeed support the notion of an association between work related
      stressors and the risk of cardiovascular disease. However, the exact biological
      mechanisms conferring this risk remain in part elusive. The general stress model
      of allostasis and allostatic load may allow studying possible pathways in more
      detail and within a common conceptual framework. Allostasis refers to the often
      useful acute stress reaction that prepares the organism for flight or fight
      threatening situations. Allostatic load summarizes the wear and tear inflicted
      upon the organism after repeated or dysregulated allostatic efforts. The
      framework of allostasis and allostatic load permits to investigate the direct
      effect of work related stressors on the primary stress reaction (reduced vagal
      tone, increased sympathetic tone and increased activity of the hypothalamic
      pituitary-adrenal axis) as well as the effect on biological process, which are
      regulated by the acute stress reaction. Longitudinal studies have shown an
      inverse association between a score operationalizing allostatic load by means of
      10 biological measures and functional status/mortality. These studies in elderly
      individuals remain to be replicated using the same framework for working age
      populations.

PMID- 14669708
TI  - [Depression, stress and coronary heart disease--epidemiology, prognosis and
      therapeutic sequelae].
AB  - Depression and coronary heart disease may be related in several ways: (1) There
      is epidemiological evidence that high levels of depressive symptoms in male and
      female patients are associated with an increased risk of myocardial infarction
      and a higher mortality following an acute cardiac event. Furthermore, patients
      developing depression after myocardial infarction have more complications,
      including cardiac arrhythmias. (2) In patients with a chronic coronary heart
      disease depression also results in a worse cardiac functional status with more
      frequent and severe chest pain, more physical limitation, less treatment
      satisfaction and a lower perceived quality of life. Non-compliance with drug
      therapy is also more prevalent in depressed cardiac patients. (3) The possible
      pathophysiological mechanisms leading to more frequent complications of coronary
      heart disease in patients with depression are not fully explained, but could
      partly be due to higher sympatho-adrenergic stimulation and increased platelet
      aggregation. Some anti-depressant medications, on the other hand, may also cause
      cardiac symptoms and increase the risk in patients with coronary heart disease.
      The use of tricyclic antidepressants has been shown to result in a higher
      relative risk of myocardial infarction even after adjustment for other
      cardiovascular risk factors. Tricyclic anti-depressants may have direct cardiac
      effects, such as QT-prolongation with ventricular arrhythmias, orthostatic
      hypotension and, less frequently, myocardial dysfunction. In contrast such
      associations were not found with the newer serotonin re-uptake inhibitors. What
      are the practical consequences of the observed association between coronary
      artery disease and depression? First of all depression should better and earlier
      be recognised also by non-psychiatrists and treatment indications be discussed
      with specialists. At present, however, there is no clear evidence that ant
      depressant drugs or psychotherapy will reduce the risk of myocardial infarction
      and improve prognosis. Further data are urgently needed to clarify the role of
      therapeutic interventions. Therefore, a closer research co-operation between
      cardiologists and psychiatrists should be promoted in future.

PMID- 14669709
TI  - [Diagnosis and therapy of depression in the heart disease patient].
AB  - Even though depressions and depressive symptoms are frequently observed in
      patients with medical diseases, their psychological problems are often neither
      diagnosed nor treated. Diagnosis of mood state might be easy in isolated cases
      yet it often is not since the precise nature of normal mood cannot be expressed
      in quantitative terms. Furthermore, depression can only be diagnosed based on the
      doctor's clinical appraisal and the patient's own description of his/her
      complaints. There is no gold standard on which depressive symptoms can be based
      on--and further on, depression is not a diagnosis. Instead, it is a syndrome that
      calls for differential diagnoses before treatment can be offered. Diagnosing
      depressive comorbidity in patients with medical complaints is even more difficult
      because of the overlap between symptoms of depression and accompanying symptoms
      of the somatic illness e.g. lack of energy. Although depressive states have been
      known to be a risk factor for the prognosis of patients with coronary heart
      disease for a long time, there is a paucity of research about the therapy these
      patients undergo due to the fact that tricyclic anti-depressants can have
      cardiotoxic effects on patients with heart disease. The treatment of depression
      in these patients has become a much lower risk since the introduction of
      serotonin reuptake inhibitors. There is widespread evidence that depressive
      comorbidity has a negative impact on the prognosis of medical disorders. Despite
      the complex nature of diagnosing depression, proper diagnosis and treatment is
      increasingly important in internal medicine and especially cardiology.

PMID- 14669710
TI  - New frontiers for the health promotion journals' equity project.

PMID- 14669711
TI  - Equity: a challenge for the future in a multi-cultural world.

PMID- 14669712
TI  - Judging the success of the Global Programme on Health Promotion Effectiveness.

PMID- 14669713
TI  - New developments for effectiveness systematic reviews in health promotion:
      cochrane Health Promotion and Public Health Field.

PMID- 14669714
TI  - Software to assist with programme planning: two community-based cases.

PMID- 14669715
TI  - [The influence of the time of death, Ca ions and NO on the reactivity of rat's
      caudal artery regulated by arginine-vasopressin].
AB  - The contraction of arteries is influenced by many factors. The aim of this
      research was to analyze how an artery's reactivity, regulated by arginine
      vasopressin changes in time, from the moment of death onwards. The research was
      conducted on rats' perfundated caudal arteries in four different time groups,
      with reference to two independent empirical models: I--with the sole use of
      intracellular Ca ions; and model II--with the sole use of extracellular Ca ions.
      The influence of NO on the arteries was analyzed in the two models, with the use
      of the NOS inhibitor. The research had shown that with the passing of time,
      beginning from the moment of death onwards, the process of emission of
      intracellular Ca ions and the infusion/transport of Ca ions from extracellular
      areas/spaces is inhibited. The use of the NOS inhibitor increases the artery's
      reactivity provided that the infusion of Ca ions from extracellular areas is also
      prevalent.

PMID- 14669716
TI  - [Locus DYS 439--polymorphism in Polish population].
AB  - This paper describes the polymorphism of a new locus DYS439 in a Polish
      population sample of 198 males. To correctly type DYS439 alleles, a sequenced
      allelic ladder was constructed. In an analyzed population sample 6 of 7 alleles
      identified to date were found (17, 19-23). The most frequent allele was 19 with a
      frequency of 0.4343. Calculated gene diversity value for DYS439 locus is 0.70 and
      is one of the highest for Y-STR loci analyzed in our population to date. Moreover
      a comparison of homogeneity distribution of DYS 439 alleles between different
      populations was analyzed. Very significant statistical differences (p < 0.0000)
      were observed between our population and four European population samples (Italy,
      Portugal and Spain).

PMID- 14669717
TI  - [Determination of polymorphic DNA sequences STR-PCR in decomposed human tissues].
AB  - This paper reports the possibility of DNA profiling obtained from soft tissues
      influenced by the decomposition process: heart, kidney, liver collected during
      autopsy. As a control DNA, profile from blood was determined. DNA was extracted
      by the phenol-chloroform method. Amplification was performed with the use of the
      GenePrintSTR Multiplex (CSF1PO, TPOX, TH01) system, Promega and AmpF[symbol: see
      text]STR Identifier, Applied Biosystems. PCR products of the CTT system were
      separated by electrophoresis on denaturing polyacrylamide gels and visualized by
      silver staining. The 16 loci of AmpF[symbol: see text]STR Identifier products
      were analyzed by capillary electrophoresis on an ABI PRISM 310 sequencer. The
      results from both methods were compared. Electrophoresis of the CTT products
      showed clear results for DNA extracted from blood and decomposed tissues,
      particularly from the heart and kidney. The capillary electrophoresis method gave
      a positive signal for all 16 loci of AmpF[symbol: see text]STR Identifier for DNA
      extracted from heart, kidney and blood. Worse results similar to the manual
      method were obtained for DNA extracted from the liver. The soft tissues, also
      decomposed by putrefaction can be a useful source of genomic DNA in personal
      identification and paternity testing.

PMID- 14669719
TI  - [The case of combination suicide].
AB  - The reported case concerns a rare method of committing suicide consisting in
      selfburning and neck incision wound made by bandsaw. The corpse of a 32 year old
      carpenter was found on the floor. The band-saw was lying nearby. Extensive wound
      on the lateral, right surface of the neck with damage to the vertebral body of C3
      was found at autopsy. This wound was made by the bandsaw. The after-burn changes
      on the lower limbs and the trunk were also found at autopsy. These changes were
      repercussions of taken attempts at suicide.

PMID- 14669718
TI  - [Theoretical bases of electrical processes in epithelial tissue].
AB  - In this study the basic electrophysiological ideas are presented and the
      electrical processes in epithelial tissues connected with the mechanisms of
      transepithelial ion transport. Knowledge of electric phenomena which takes place
      in epithelium after circulatory arrest, can contribute to the future explanation
      of the mechanisms which accompany interlethal reactions.

PMID- 14669720
TI  - [Unusual case of gunshot by self-made firearm].
AB  - A case of suicide with the use of a primitive self-made firearm, constructed with
      a steel tube was presented. Victim standing on a stool, with hanging loop around
      neck, shot himself to mouth with fourteen steel balls. At this moment the weapon
      tore apart wounding hand of the victim.

PMID- 14669721
TI  - [Intoxication as an "ever lasting problem"].
AB  - Medicolegal opinion of insobriety considering retrospective and prospective
      calculation, analytical methods and other problems have been constructed for the
      needs of law and lawyers. Their substantial correctness cornus the basis of a
      good level of medicolegal expert's opinion. This is the reason that each paper
      including this one concerning the subject of a key point of an opinion, possible
      mistakes, traps or controversial aspects of problems contributes to a permanent
      improvement of opinions related insobriety.

PMID- 14669722
TI  - [Evaluation of genetic relationship in the pair: putative father--child without
      the child's mother examination].
AB  - In this paper author shows that the living mother plays an important role in
      examinations of genetic relationship in paternity testing.

PMID- 14669723
TI  - Meeting notes from the 2nd International AIDS Society Conference on HIV
      Pathogenesis and Treatment. Trizivir vs. efavirenz: results from ACTG 5095.
AB  - An oral presentation reviewed data from a discontinued study comparing triple
      NRTI therapy with 2 efavirenz-containing regimens.

PMID- 14669724
TI  - Meeting notes from the 2nd International AIDS Society Conference on HIV
      Pathogenesis and Treatment. Metabolic update: better defining lipodystrophy and
      treating insulin resistance.
AB  - A large case-control study finds that lipoatrophy is the predominant fat
      abnormality in HIV-infected patients, and a small randomized, placebo-controlled
      study finds benefit for rosiglitazone for insulin resistance.

PMID- 14669725
TI  - Meeting notes from the 2nd International AIDS Society Conference on HIV
      Pathogenesis and Treatment. Resistance rates in treatment-naive patients.
AB  - In a study of newly diagnosed patients in Europe, resistance rates were similar
      in patients who had been infected in the past year and in those who had been
      infected longer.

PMID- 14669726
TI  - Meeting notes from the 2nd International AIDS Society Conference on HIV
      Pathogenesis and Treatment. New drugs.
AB  - Several industry-supported studies provide information on new drugs in various
      stages of development, including the PIs tipranavir, TMC-114, and 908 (the
      amprenavir prodrug), and the NRTI SPD754.

PMID- 14669727
TI  - Meeting notes from the 2nd International AIDS Society Conference on HIV
      Pathogenesis and Treatment. Exploring once-daily tenofovir + 3TC + abacavir: an
      argument for clinical-trials-based data.
AB  - In the first formally presented data on once-daily tenofovir + 3TC + abacavir,
      the regimen is shown to be suboptimal. Problem is, clinicians have already been
      using it.

PMID- 14669728
TI  - WTO accepts rules limiting medicine exports to poor countries.
AB  - In a controversial decision on August 30, 2003, the World Trade Organization
      agreed to complex rules limiting the export of medications to developing
      countries. Reaction to the decision so far has shown a complete disconnect
      between trade delegates and the WTO, both of which praise the new rules as a
      humanitarian advance, and those working in treatment access in poor countries,
      who believe that they will effectively block treatment from reaching many who
      need it. We have prepared a background paper that analyzes this decision and its
      implications and offers the opinions of key figures on both sides of the debate.
      It is clear that the rules were largely written for and probably by the
      proprietary pharmaceutical industry, and imposed on the countries in the WTO
      mainly by the United States. The basic conflict is that this industry does not
      want the development of international trade in low-cost generic copies of its
      patented medicines--not even for poor countries, where little or no market
      exists. Yet millions of people die each year without medication for treatable
      conditions such as AIDS, and drug pricing remains one of several major obstacles
      to controlling global epidemics.

PMID- 14669729
TI  - Nevirapine reduced mother-to-child transmission better than AZT--at 70 times less
      the cost.
AB  - A follow-up of a Uganda study shows that a single dose of nevirapine to the
      mother in labor and a single dose to the infant shortly after birth continues to
      show excellent results when the infants reach 18 months--despite breast feeding
      for 99% of the infants, and some HIV transmission that occurred as a result.

PMID- 14669730
TI  - Treatment interruption: study found poor result for highly treated, highly
      resistant patients.
AB  - A four-month treatment interruption did not help patients who were not
      controlling their virus because it had extensive resistance to HIV drugs.

PMID- 14669731
TI  - New guidelines for avoiding heart disease by managing high cholesterol,
      triglycerides, or related problems in HIV.
AB  - These guidelines, based on new heart guidelines for the general public and
      including HIV-specific issues, have many useful suggestions.

PMID- 14669732
TI  - Cyberdating. How can I find Mr. Right with so many Mr. Wrongs out there on the
      Internet?

PMID- 14669733
TI  - Lean on them...and each other. Profiles of three BP support groups and their
      volunteer facilitators.

PMID- 14669734
TI  - Help is just a call away. The Body Positive Helpline.

PMID- 14669735
TI  - Flying right: vacation planning tips for those with HIV.

PMID- 14669736
TI  - Antiretroviral drug guide 2003.

PMID- 14669737
TI  - Avoiding 'treatment anarchy'.

PMID- 14669738
TI  - US FDA approves Emtriva (FTC).

PMID- 14669739
TI  - [Advances in the study of bee venom and its clinical uses].

PMID- 14669740
TI  - [A review on the study of Resina Draconis produced in China].

PMID- 14669742
TI  - Snapping the fingers.

PMID- 14669741
TI  - [Advances in the study of Eucalyptus globulus Labill].

PMID- 14669743
TI  - "Picture that". Introducing elementary school children to nursing.

PMID- 14669744
TI  - Reconstruction of fingertip amputations with advancement flaps and nail bed full
      thickness.

PMID- 14669745
TI  - The first professional.

PMID- 14669746
TI  - ACE-inhibition and angiotensin II receptor blockers in chronic heart failure:
      pathophysiological consideration of the unresolved battle.
AB  - Reducing the effects of angiotensin II by blockade of AT1-receptors may be
      superior to inhibition of angiotensin II formation by angiotensin converting
      enzyme (ACE) inhibitors in chronic heart failure (CHF) patients. However, the
      results of several trials did not fulfil this expectation. In both ELITE II with
      symptomatic CHF patients and in OPTIMAAL involving high risk patients after acute
      myocardial infarction, angiotensin II type I (AT1) receptor blocker (ARB)
      losartan did not prove to be superior to captopril. There are several potential
      reasons, why ARBs did not fare better than ACE inhibitors. Although AT1-receptor
      blockade may block the effects of non-ACE pathways of tissue angiotensin II
      formation, no clinical evidence is available that a more powerful inhibition of
      the tissue renin-angiotensin system brings improved survival. The choice of
      patients for clinical trials of HF therapy is not based on the level of
      neurohumoral activation. Thus, the more effective attenuation of angiotensin II
      action with ARBs may not bring additional benefits. The potential antiremodeling
      effect of ARBs through the stimulation of AT2 receptors by angiotensin II could
      be counterbalanced by a failure of AT1-receptor blockers to enhance bradykinin,
      nitric oxide and prostacyclin formation with antigrowth properties. Although ACE
      inhibitors seem to have slightly better results at present than AT1 blockers in
      the battle on heart failure patient, future trials will decide which is the
      definitive winner.

PMID- 14669747
TI  - Plasma concentration profile of orally administered pimobendan and plasma brain
      natriuretic peptide level in patients with severe heart failure.

PMID- 14669748
TI  - A case of severe diabetes mellitus occurred during management of heart failure
      with carvedilol and furosemide.

PMID- 14669749
TI  - [Hepatolenticular degeneration complicated with acute hematolysis and acute liver
      failure: report of one case].

PMID- 14669750
TI  - The first "Award to Active Cities Contest" for the Region of the Americas.

PMID- 14669751
TI  - Current readings in nuclear medicine.

PMID- 14669752
TI  - Is parenteral nutrition guilty?

PMID- 14669753
TI  - [Investigation of single nucleotide polymorphisms in the promoter region of
      mannan-binding lectin gene in a Han population from Guangdong].
AB  - OBJECTIVE: To investigate the single nucleotide polymorphisms (SNP) in the
      promoter region of mannan-binding lectin (MBL) gene in a Han population in
      Guangdong Province. METHODS: A total of 167 blood samples were obtained from this
      Han population to isolate the genomic DNA from the leucocytes. The polymorphism
      alleles -550(G/C, named H/L alleles), -220(G/C, X/Y alleles) and +4(C/Tr, P/Q
      alleles) in the promoter region of MBL gene were detected by PCR with sequence
      specific primers and molecular beacon real-time fluorescent PCR, and the
      frequencies of haplotypes and genotypes were analyzed. RESULTS: The frequencies
      of several genotypes in the 167 samples were: LYP/LYP, 10(5.9%); HYP/LYQ,
      7(4.2%); LYP/LYQ, 94(56.3%); LXP/LXP, 6(3.6%); LYQ/LYQ, 4(2.4%); LXP/LYQ,
      29(17.4%); HYP/LYP, 3(1.8%); HYP/LXP, 2(1.2%); HYP/HYP, 12(7.2%). CONCLUSION: The
      polymorphism genotypes in the promoter region of MBL gene in this chosen
      population are mostly LYP/LYQ and LXP/LYQ.

PMID- 14669754
TI  - Hemodynamic assessment: the technique or the physician at fault?

PMID- 14669757
TI  - [Sertoli-cell-only syndrome: report of one case].

PMID- 14669755
TI  - Acute bacterial meningitis: time for a better outcome.

PMID- 14669756
TI  - Triggering and cycling off during pressure support ventilation: simplicity or
      sophistication?

PMID- 14669758
TI  - [Anatomically repairing Taussig-Bing abnormality treated by Rastelli procedure
      and allograft valved external conduit: report of 4 cases].

PMID- 14669759
TI  - Ruth Krueger reflects on war and a lifetime of nursing.

PMID- 14669761
TI  - [Pretibial myxedema treated with cortisone acetate: report of one case].

PMID- 14669760
TI  - [Treatment of complex hepatic echinococcosis by surgical removal of the internal
      capsule plus external drainage: experience with 31 cases].

PMID- 14669762
TI  - [Successful management of severely burned patients: report of 6 cases].

PMID- 14669763
TI  - Variability in interventions with pulmonary artery catheter data.
AB  - OBJECTIVES: To determine if intensivists given PAC data from critically ill
      patients make uniform management choices. DESIGN: Cross-sectional survey of board
      certified intensivists. SETTING: Medical intensive care unit. PARTICIPANTS: Board
      certified intensivists who are members of the American College of Chest
      Physicians and Society of Critical Care Medicine. INTERVENTIONS: A survey
      questionnaire containing three medical intensive care clinical vignettes was
      mailed to critical care physicians. Each vignette contained PAC data and one-half
      of the surveys contained echocardiographic (Echo) information. Every respondent
      was asked to select one of six interventions for each vignette. MEASUREMENTS:
      There were 126 evaluable surveys returned. In vignette 1 an intervention (none of
      the above) was selected by more than 50% of respondents. In vignettes 2 and 3,
      the most frequent selection was chosen only 44 and 37% of the times,
      respectively. There was a significant difference in the distribution of
      management choices between te Echo and the non-Echo subgroups. CONCLUSIONS: There
      is a significant heterogeneity in selecting an intervention based on PAC data
      among intensivists. The presence of Echo information may change the intervention
      selected but does not reduce heterogeneity. Any randomized trial evaluating
      efficacy of PAC's will have to have strict treatment protocols.

PMID- 14669764
TI  - Noninvasive continuous positive airway pressure ventilation using a new helmet
      interface: a case-control prospective pilot study.
AB  - OBJECTIVE: To evaluate the clinical efficacy of noninvasive continuous positive
      airway pressure ventilation (CPAP) using a new interface, constituted by a
      cephalic plastic helmet, in comparison with a standard facial mask. DESIGN AND
      SETTING: A prospective pilot study with matched-control group, in the emergency
      department of a teaching hospital. PATIENTS AND METHODS: Eleven consecutive adult
      patients with acute hypoxemic respiratory failure related to cardiogenic
      pulmonary edema (whether hypercapnic or not) were enrolled in the study, after
      failure of the initial medical treatment. Each patient treated with CPAP, using
      the helmet in addition to a standardized medical treatment, was matched with
      historical control-patient treated with CPAP using a standard facial mask, and
      selected by gender, age, and PaCO2 levels on admission. Primary end points were
      improvements of gas exchanges and clinical parameters of respiratory distress.
      tolerance was evaluated after each CPAP trial. RESULTS: The 22 patients and
      controls had similar characteristics at baseline. PaCO2 levels, and clinical
      parameters improved similarly in both groups. No interface intolerance was
      reported whether using standard facial mask or the helmet. No complications were
      observed in either group. The helmet allowed CPAP administration for a longer
      period of time (p=0.045). In-hospital mortality was not different between the two
      groups. CONCLUSION: Despite a high dead-space volume (9-15 l), this new helmet
      interface is an efficient alternative to standard face mask during CPAP, even in
      cases of severe respiratory acidosis and hypercapnia. It allowed to provide long
      duration CPAP, without any adverse events or clinical intolerance.

PMID- 14669765
TI  - [Comparison of 2 different invitation methods for mammography screening].

PMID- 14669766
TI  - The humoral response in the pathogenesis of gluten ataxia.

PMID- 14669767
TI  - Clinical recommendations appended to cervical cytology reports.

PMID- 14669768
TI  - Prediction of risk for respiratory distress syndrome using gestational age and
      the TDx-FLM II assay.

PMID- 14669769
TI  - Prediction of respiratory distress syndrome.

PMID- 14669770
TI  - Risk assessment calculation for respiratory distress syndrome.

PMID- 14669771
TI  - Radical trachelectomy.

PMID- 14669772
TI  - Radical trachelectomy: a need for a careful preoperative assessment.

PMID- 14669773
TI  - Mechanical ventilation in an obstetric population.

PMID- 14669774
TI  - The history of organ transplantation in Belgium. Proceedings of the 4th Belgian
      Surgical Week. Oostende, May 1-3, 2003.

PMID- 14669775
TI  - Convergent volunteerism.

PMID- 14669776
TI  - Murine pulmonary inflammatory responses following instillation of size
      fractionated ambient particulate matter.
AB  - The mechanisms for increased cardiopulmonary disease in individuals exposed to
      particulate air pollution are associated with fine and ultrafine particles that
      have a high oxidative potential. Particulate matter (PM) from Research Triangle
      Park (NC) was collected and separated into 3 different size fractions: coarse
      (CO; >3.5 microm), fine (FI; 1.7-3.5 microm), and fine/ultrafine (FU; <1.7
      microm) using impaction and electrostatic precipitation. Particle chemistry
      indicated the presence of sulfates, zinc, iron, and copper in all fractions. CD1
      mice were intratracheally instilled with 10, 50, or 100 microg of each fraction.
      After 18 h, the lungs were lavaged and assayed for signs of inflammation. All
      particles produced increases in neutrophil number, and this was highest in the
      high-dose FU group. Biochemical analysis revealed ni change in lactate
      dehydrogenase (LDH) activity, and increased albumin and tumor necrosis factor
      (TNF)-alpha levels were only seen with the high-dose FI particles. Interleukin 6
      (IL-6) levels were increased over control levels after treatment with 100 microg
      of all 3 particle sizes. To determine whether oxidative stress may contribute to
      these effects, antioxidant levels in the ling were boosted by an intraperitoneal
      (ip) injection with dimethylthiourea (DMTU). This treatment resulted in a twofold
      increase in the total antioxidant capacity of the lung and decreased the PM
      induced cytokine and neutrophil influx up to 50%. The data indicate that on the
      equal mass basis, ambient particles of these three size ranges produce pulmonary
      inflammation, and that increasing the antioxidant capacity of the lung reduces
      particle-induced cytokine and cellular responses.

PMID- 14669777
TI  - The lack of science behind the standard of care.

PMID- 14669778
TI  - Mobile hyperbaric chamber: an essential need in emergency medicine?

PMID- 14669780
TI  - Abstracts of the 2nd World Conference of the International Study Group on
      Neuroendoscopy (ISGNE). Naples, Italy, 11-13 September 2003.

PMID- 14669779
TI  - Uterine prolapse and cystocele after an automobile accident.

PMID- 14669781
TI  - Tendon--bridging the gap. Proceedings of a symposium held at the Society for
      Integrative and Comparative Biology Annual Meeting. Anaheim, California, USA.
      2002.

PMID- 14669782
TI  - Proceedings of the 16th Congress of the International Society of Fibrinolysis and
      Proteolysis (ISFP) in conjunction with the 17th Workshop of the International
      Fibrinogen Research Society (IFRS). Munich, Germany, September 8-12, 2002.

PMID- 14669783
TI  - Carotid artery angioplasty: current status.

PMID- 14669784
TI  - Stamping about SARS.

PMID- 14669785
TI  - Research on subjects incapable of giving informed consent: the situation in Dutch
      intensive care departments.

PMID- 14669787
TI  - Nobel Prize 2003 in Physiology and Medicine.

PMID- 14669788
TI  - Suppression of pancreatic cancer cell invasion by a cyclooxygenase-2-specific
      inhibitor.
AB  - Pancreatic cancer is characterized by invasive and metastatic potential. In this
      study, effects of the COX-2 inhibitor JTE-522 on cell viability, invasion, and
      invasion-related cellular properties were determined. JTE-522 (10 microM) induced
      a 75-90% reduction in invasion, compared to cells treated with a vehicle only, in
      the COX-2-expressing cells. In contrast, this inhibitor caused no significant
      reduction in cells lacking COX-2. Determinants of cell invasion, such as cell
      motility, adhesion to the extracellular matrix, and gelatinolytic activity of
      metalloproteinase, were also modulated in COX-2-positive pancreatic cancer cells.
      Thus, COX-2-specific inhibitors may be a useful anti-invasive therapeutic option
      in pancreatic cancer.

PMID- 14669789
TI  - Inhibitory effect of antisense aminopeptidase N (APN/CD13) cDNA transfection on
      the invasive potential of osteosarcoma cells.
AB  - Aminopeptidase N (APN/CD13), a Zn2+-dependent ectopeptidase, is localized on the
      cell surface and functions as a transmembrane protein. Increased expression and
      activity of APN have been postulated to correlate with the aggressive behavior of
      several tumor types. In this study, the osteosarcoma cell line MNNG/HOS was
      stably transfected with an expression vector capable of expressing the antisense
      transcript of APN. Four stably transfected clones, the control clones and
      parental cells were characterized. Stable integration of the antisense vector was
      confirmed by PCR analysis of genomic DNA. Competitive RT-PCR revealed that mRNA
      expression of antisense-transfectants was decreased to approximately 37% of the
      control cell line. The activity assay showed that the enzymatic activity of APN
      was inhibited to approximately 51% of the control cell line. Antisense
      transfection had no influence on the cellular proliferation measured by the 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, on the
      motility in Transwell chambers, and on the adhesive potential to collagen I.
      However, an in vitro invasion assay revealed a significant decrease in the number
      of cells that migrated through a reconstituted membrane (51% of the control cell
      line). The adhesive potential to Matrigel was also affected (73% of the control
      cell line). Furthermore, under in vivo conditions, a reduced potency to
      metastasize to the lung was shown in an experimental metastasis assay in nude
      mice. These findings demonstrate that APN plays an active role in the cellular
      attachment and proteolytic degradation of the extracellular matrix in the
      metastatic process of osteosarcomas.

PMID- 14669790
TI  - The meaning of the c-kit proto-oncogene product in malignant transformation in
      human mammary epithelium.
AB  - To evaluate the relationship between the c-kit proto-oncogene product and
      malignant transformation of human breast tissue, we examined the
      immunohistochemical expression of the c-kit proto-oncogene product in both
      malignant and non-malignant breast tissues. The immunohistochemical expression of
      the c-kit proto-oncogene product in 40 primary breast cancer tissues (22 axillary
      lymph nodes negative, 18 lymph nodes positive), in 18 corresponding axillary
      lymph nodes, and in 10 distant metastastic tissues were studied using an anti-c
      kit proto-oncogene product antibody in comparison with 20 normal and 20 benign
      breast tissues. The mean values of immunoreactive score (IRS) were compared. The
      IRS of the c-kit proto-oncogene product in normal mammary epithelia was 5.90 +/-
      1.37 (mean +/- s.d.). In benign tissues, the c-kit proto-oncogene product was
      detected heterogeneously with a reduced IRS (4.05 +/- 1.82). In primary breast
      cancer tissues, the expression of the c-kit proto-oncogene product was often
      deleted and the average IRS (0.90 +/- 1.73) was significantly reduced compared to
      those of the normal breast tissues or benign breast disease tissues, but no
      significant difference was shown between the breast cancer groups. The c-kit
      proto-oncogene product may correlate with growth control or the differentiation
      of normal breast epithelium. This result suggests that the loss of expression of
      this protein might correlate with malignant breast cancer progression, but it is
      most likely involved at an early stage of human breast cancer development.

PMID- 14669791
TI  - Expression of the 67 kDa laminin receptor and the alpha6 integrin subunit in
      serous ovarian carcinoma.
AB  - The aim of this study was to analyze the expression of two laminin receptors, the
      67 kDa laminin receptor (LBP) precursor and the alpha6 integrin subunit, in
      effusions and solid tumors of patients diagnosed with serous ovarian carcinoma
      and to evaluate their predictive role. Eighty-eight effusions and one hundred
      sixteen primary (= forty-one) and metastatic (= seventy-five) ovarian carcinomas
      were evaluated for expression of the above-mentioned mRNAs using in situ
      hybridization (ISH). LBP protein expression was studied in 24 effusions and 43
      solid tumors using immunohistochemistry (IHC). Alpha6 integrin subunit protein
      expression was studied in 27 effusions using flow cytometry (FCM). Expression of
      LBP mRNA was frequently detected in both carcinoma (92 of 116 cases, 79%) and
      stromal (79 of 116 cases, 68%) cells in solid tumors. Expression was still higher
      in cancer cells in effusions (85 of 88 specimens, 96%). In contrast, alpha6
      integrin subunit was less frequently detected in both solid tumors (33 of 116;
      28% in carcinoma cells, 23 of 116; 20% in stromal cells) and effusions (36 of 88;
      41%). LBP protein expression was found in 19 of 24 (79%) effusions and 40 of 43
      (93%) solid tumors, and was higher in effusions of patients who received
      chemotherapy prior to tapping (P = 0.024). FCM showed protein expression of the
      alpha6 integrin subunit in 17 of 27 (63%) effusions. Expression of the alpha6
      integrin subunit mRNA in tumor cells of solid lesions was significantly lower in
      solid tumors of FIGO stage-IV patients compared to those of patients diagnosed
      with stage-III-disease (P = 0.004), and its absence predicted significantly
      shorter overall survival (OS) in univariate analysis (P = 0.018). Absence of
      alpha6 integrin subunit protein expression using FCM predicted median OS of 12
      months compared to 26 months for patients with tumors expressing the protein,
      although this finding did not reach significance (P = 0.27). In conclusion, as
      opposed to previous reports, both mRNA and protein expression of the alpha6
      integrin subunit do not appear to be down-regulated in effusions compared to
      solid tumors. Loss of alpha6 integrin subunit mRNA (and possibly protein)
      expression is a novel prognostic marker in advanced-stage ovarian carcinoma. LBP
      mRNA and protein expression is independent of that of the alpha6 integrin subunit
      in both solid tumors and effusions of serous ovarian carcinoma.

PMID- 14669792
TI  - Structural examination of tryptase- and chymase-positive mast cells in livers,
      containing metastases from gastrointestinal cancers.
AB  - Human mast cells are categorized into mast cells positive only for tryptase
      (MC(T)) and mast cells positive for both tryptase and chymase (MC(TC)). The
      structural appearance of tryptase-, and chymase-positive mast cells in metastatic
      liver disease and the variations in MC(T) and MC(TC) numbers in accordance with
      the origin of the primary tumors have been described in the present study. Liver
      mast cells are analyzed immunocytochemically using tryptase and chymase and by
      quantitative morphometry in 30 patients with colorectal (n = 15), gastric (n =
      8), and pancreatic (n = 7) cancers and in 5 control livers. The numbers of MC(T)
      and MC(TC) are increased in the extratumoral liver tissue (mainly portal tracts)
      as compared to controls. The numbers of MC(T) and MC(TC) in and around metastases
      with moderate or high grade of differentiation are statistically significantly
      higher, as compared to those with low grades of differentiation. The numbers of
      MC(TC) are greater than that of MC(T) in the extratumoral liver tissue and in
      metastases themselves. Ultrastructurally, mast cells immunostained with tryptase
      and chymase have three types of granules: electron dense granules with darkly
      precipitated reaction product, electron lucent granules without reaction product
      and electron lucent granules with sparse reaction product (altered granules).
      Both types of mast cells have small and large in size granules, resembling the
      MC(TC) phenotype described earlier. Tryptase-positive mast cells have granules
      with discrete scrolls and particulate and beaded pattern. Chymase-positive mast
      cells have granules with finely granular or particulate material. Substance P
      (SP)- and vasointestinal polypeptide (VIP)-positive mast cells are not observed
      in livers with metastases. The present study suggests that liver mast cells are
      mainly from the MC(TC) type, and are accumulated in peritumoral and metastatic
      areas. They may play a role in the formation of tumor stroma, or in tumor
      immunology in liver metastases from various primary gastrointestinal cancers.

PMID- 14669794
TI  - Real-time imaging of individual fluorescent-protein color-coded metastatic
      colonies in vivo.
AB  - We have established stable, bright green fluorescent protein (GFP)- or red
      fluorescent protein (RFP)-expressing HT-1080 human fibrosarcoma clones. These
      cell lines showed similar cell proliferation rates and high-frequency
      experimental lung metastasis. The HT-1080-GFP and -RFP clones enable simultaneous
      real-time dual-color imaging in the live animal. HT-1080 cells were transduced
      with retroviral vectors containing GFP or RFP and the neomycin resistance gene.
      Stable transformants were selected stepwise with G418 up to 800 microl/ml.
      Subsequently, high GFP- or RFP-expressing clones, HT-1080-GFP or HT-1080-RFP,
      respectively, were selected. 3 x 10(6) cells from each clone were mixed and
      injected into the tail vein of SCID mice. The cells seeded the lung at high
      frequency with subsequent formation of pure green and pure red colonies as well
      as mixed yellow colonies with different patterns visualized directly on excised
      lungs. The lung metastases were also visualized by external fluorescence imaging
      in live animals through skin-flap windows over the chest wall. Lung metastases
      were observed on the lung surface of all mice. SCID mice well tolerated multiple
      surgical procedures for direct-view imaging via skin-flap windows. Real-time
      metastatic growth of the two different colored clones in the same lung was
      externally imaged with resolution and quantification of green, red, or yellow
      colonies in live animals. The color coding enabled determination of whether the
      colonies grew clonally or were seeded as a mixture with one cell type eventually
      dominating, or whether the colonies grew as a mixture. The simultaneous real-time
      dual-color imaging of metastatic colonies described in this report gives rise to
      the possibility of color-coded imaging of clones of cancer cells carrying various
      forms of gene of interest.

PMID- 14669793
TI  - Matrix metalloproteinases (MMP), EMMPRIN (extracellular matrix metalloproteinase
      inducer) and mitogen-activated protein kinases (MAPK): co-expression in
      metastatic serous ovarian carcinoma.
AB  - Activation or suppression of intracellular signaling via the mitogen-activated
      protein kinase (MAPK) family has been linked to expression of matrix
      metalloproteinases (MMP) in experimental models, but this association has not
      been demonstrated in clinical material. The objective of this study was to
      investigate the possible association between expression and activity of MMP,
      expression of the MMP inducer EMMPRIN, and the expression (level) and
      phosphorylation status (activity) of the extracellular-regulated kinase (ERK), c
      Jun amino-terminal kinase (JNK) and high osmolarity glycerol response kinase
      (p38) in effusions from patients diagnosed with serous ovarian carcinoma. MAPK
      level and activity were studied in 55 effusions using immunoblotting. MMP-1, MMP
      2, MMP-9 and EMMPRIN expression was studied using immunocytochemistry (ICC) and
      mRNA in situ hybridization (ISH). The gelatinolytic activity of MMP-2 and MMP-9
      was measured by zymography. ERK and phospho-ERK (p-ERK) were detected in 54/55
      (98%) and 50/55 (91%) specimens, respectively. JNK and p-JNK were detected in
      53/55 (96%) and 38/55 (69%) specimens, respectively. p38 was expressed in 54/55
      (98%) specimens, and its phosphorylated form was found in 51/55 (92%). MMP-2 mRNA
      expression (P = 0.048), protein expression (P = 0.046) and gelatinolytic activity
      (P = 0.039) correlated with ERK phosphorylative activity. MMP-2 activity also
      correlated with p38 activity (P = 0.017). MMP-9 protein expression correlated
      with phosphorylation of p38 (P = 0.046), but enzyme activity showed inverse
      relationship with both p-ERK (P = 0.05) and p-p38 (P = 0.033) expression. EMMPRIN
      expression correlated with MMP-1 (P < 0.001), MMP-2 (P = 0.042) and MMP-9 (P =
      0.029) expression, as well as with ERK activity (P = 0.001). Our results present
      the first evidence of a possible link between MAPK signaling and MMP expression
      and activity in vivo. These data may expand our understanding regarding the
      mechanisms by which MMP synthesis is regulated in effusions and possibly affect
      treatment strategies for this form of malignancy.

PMID- 14669795
TI  - Bone marrow metastatic myeloma cells promote osteoclastogenesis through RANKL on
      endothelial cells.
AB  - We have been using the B9/BM1 murine bone marrow metastasis model to study the
      function of adhesion molecules in the cell-cell interactions and transendothelial
      migration, necessary for tumor metastasis. The cell surface phenotype of these
      cells, which colonize vertebral and femoral marrow after intravenous injection,
      shows great similarity to that of human myeloma cells. In the present study, we
      investigated the interaction between B9/BM1 cells and osteoclasts, which likely
      support tumor metastasis in bone marrow. We found that co-culturing B9/BM1 cells
      and bone marrow-derived endothelial cells (BMECs) in the presence of vitamin D3
      and M-CSF promoted differentiation of primary osteoclast progenitors to
      osteoclasts (detected by TRAP staining), and that this effect was blocked when
      BMECs were separated from the other cells by a porous polycarbonate membrane.
      Flow cytometry analysis showed that BMECs expressed RANKL (receptor activator of
      NF-kappaB ligand) protein on their surface, and that this expression was up
      regulated by co-culture with B9/BM1 cells. Accordingly, RT-PCR showed expression
      of RANKL mRNA also to be up-regulated in BMECs co-cultured with B9/BM1 cells.
      Addition of OPG (osteoprotegerin, a decoy RANKL receptor) to the co-culture
      system completely blocked osteoclast induction, as did addition of anti-CD44
      antibody. Furthermore, intravenous injection of B9/BM1 cells substantially
      increased the numbers of TRAP-positive osteoclasts detected in mice in vivo.
      Taken together, these findings suggest that B9/BM1 myeloma cells act via CD44 to
      stimulate RANKL expression on BMECs, which in turn physically interact with
      osteoclast progenitors to promote their differentiation to osteoclasts and
      metastasis in bone marrow.

PMID- 14669796
TI  - IL-2-mediated augmentation of NK-cell activity and activation antigen expression
      on NK- and T-cell subsets in patients with metastatic melanoma treated with
      interferon-alpha and DTIC.
AB  - Considering that well-defined and comprehensive immunological monitoring is the
      basis for the evaluation of the obtained immunmodulatory effects, we evaluated NK
      cell activity, the number of CD3+ CD4+, CD3+ CD8+ T cells and CD16+ CD56+ NK
      cells, as well as the expression of activation antigens, CD69, CD38 and HLA-DR on
      CD56+ NK cells, CD8+ and CD3+ T cells, simultaneously with IL-2 and TNF-alpha
      production, during chemoimmunotherapy with dacarbazine (DTIC) and interferon
      alpha (IFN-alpha) in 39 patients with metastatic melanoma. In the first cycle of
      therapy, there was a significant rise in NK-cell activity, CD4+ T helper cell
      number, CD4/CD8 T-cell ratio, and the expression of activation antigens CD69 and
      CD38, on NK and T cells, respectively. However, in the following cycles there was
      a significant increase only in activation antigens without an increase in the
      percent or activity of NK cells. The early, but transient, immunopotentiation,
      present only in the first cycle of combined DTIC and IFN-alpha therapy, suggests
      that, in spite of increased IL-2 level, associated with augmented NK-cell
      activity, this therapy has a limited effect probably owing to the adverse effect
      of persistently high level of TNF-alpha in metastatic disease.

PMID- 14669797
TI  - Increased metastatic potential in human prostate carcinoma cells by
      overexpression of arachidonate 12-lipoxygenase.
AB  - Arachidonate 12-lipoxygenase (LOX) converts arachidonic acid to 12(S)
      hydroxyeicosatetraenoic acid (HETE), a bioactive lipid implicated in tumor
      angiogenesis, growth, and metastasis. Alteration in 12-LOX expression or activity
      has been reported in various carcinomas including prostate carcinoma. However,
      little is known about the impact of the altered expression or activity of 12-LOX
      on tumor metastasis. In the present study, we examined whether or not an increase
      in 12-LOX expression in human prostate carcinoma cells can modulate their
      metastatic potential. We report that increased expression of 12-LOX in PC-3 cells
      caused a significant change in cell adhesiveness, spreading, motility, and
      invasiveness. Specifically 12-LOX transfected PC-3 cells were more adhesive
      toward vitronectin, type I and IV collagen, but not to fibronectin or laminin,
      than cells transfected with control vector. Increased spreading on vitronectin,
      fibronectin, collagen type I and IV also was observed in 12-LOX transfected PC-3
      cells when compared to control PC-3 cells. The increased spreading of 12-LOX
      transfected PC-3 cells was blocked by treatment with 12-LOX inhibitors, baicalein
      and CDC. 12-LOX transfected PC-3 cells were more invasive through Matrigel than
      cells transfected with control vector. In vivo, tumor cell invasion to
      surrounding muscle or fat tissues was more frequent in nude mice bearing s.c.
      tumors from 12-LOX transfected PC-3 cells than in those from control vector
      transfected cells. When injected via the tail vein into SCID mice with implanted
      human bone fragments, there was an increase in tumor metastasis to human bone by
      12-LOX transfected PC-3 cells in comparison to control vector transfected cells.
      Taken together, our data suggest that an increase in 12-LOX expression enhances
      the metastatic potential of human prostate cancer cells.

PMID- 14669799
TI  - Sodar mixing height estimates and air pollution characteristics over a
      Mediterranean big city.
AB  - Sodar systems are progressively used for quantitative and qualitative profile
      information on the atmospheric structure parameters. However, there is still a
      need for well-established relations between atmospheric physics parameters and
      air quality patterns, especially in urban environments. In this respect it is of
      importance to investigate the correlations among specific atmospheric quantities
      and air pollution patterns. It is the purpose of this paper to study correlations
      between the Sodar produced mixing height using the most recent and accurate
      methods, and O3, NOx and CO concentrations recorded by the Athens air quality
      monitoring network, during selected meteorological conditions. The continuous
      mixing height monitoring allows for deeper investigation of air pollution
      characteristics, especially during the transitional periods of the day. The
      obtained results indicate that there is good correlation between the pollutants
      concentrations and the mixing height especially during episode days. Furthermore,
      it is indicated that there is a strong dependence between the rate of increase of
      the mixing height and the concentration levels in the early morning hours as well
      as during the Atmospheric Boundary Layer (ABL) collapse in the afternoon. These
      results are of importance for urban air pollution modelling, which has recently
      attracted the attention of many research groups.

PMID- 14669798
TI  - Biological properties and gene expression associated with metastatic potential of
      human osteosarcoma.
AB  - Lung metastasis has a great influence on the prognosis of patients with
      osteosarcoma. We previously established two high-metastatic sublines, M112 and
      M132, from the HuO9 human osteosarcoma cell line by in vivo selection. In this
      study, we newly isolated a high-metastatic subline, H3, and three low-metastatic
      sublines, L6, L12 and L13, from HuO9 by the dilution plating method. Three high
      metastatic sublines produced more than 200 metastatic nodules in the lung, while
      three low-metastatic sublines produced no or few nodules after injection of 2 x
      10(6) cells into the tail vein of nude mice. There were significant differences
      in the motility and invasiveness between high- and low-metastatic sublines,
      whereas the growth rates in vitro and the tumorigenicity in vivo showed no
      correlation with their metastatic abilities. Early adherence to culture plates
      was significantly lower in two of three low-metastatic sublines, which occupied
      smaller surface areas on the culture plates than other sublines did. Comparison
      of the expression of 637 cancer-related genes by cDNA microarray revealed that
      seven genes were differentially expressed between high- and low-metastatic
      sublines. Among them, five genes (AXL, TGFA, COLL7A1, WNT5A, and MKK6) were
      associated with adherence, motility, and/or invasiveness. These results suggest
      that the differences in motility/invasiveness and adhesive abilities are key
      determinants of lung metastasis in osteosarcoma.

PMID- 14669800
TI  - VOCs isotherms on day zeolite by static and dynamic methods: experiments and
      modelling.
AB  - A dynamic method and a static gravimetric method are respectively used to measure
      the adsorption equilibria of m-xylene and n-butyl acetate on Wessalith DAY
      zeolite F20. The equilibrium experiments are performed at different temperatures
      for both volatile organic compounds (VOCs). The m-xylene isotherms obtained in
      this study by the dynamic method are compared to our recently published data in
      which the static gravimetric method was used in order to test the influence of
      the experimental technique. Because the adsorption isotherms of m-xylene were
      correlated in our previous paper, in this study only the n-butyl acetate
      experimental data are correlated with various adsorption isotherm models:
      Langmuir, Toth and Dubinin equations.

PMID- 14669801
TI  - Effects of oil and bioremediation on mussel (Mytilus edulis L.) growth in
      mudflats.
AB  - Mussels (Mytilus edulis L.) were exposed to crude oil during a field experiment
      to evaluate two bioremediation strategies (nutrient addition and nutrient
      addition with tilling). The mussels were placed in 4 mesocosms: Control, Oil, Oil
      + Nutrients, and Oil + Nutrients + Tilled. Tilling appeared to be clearly
      detrimental to mussel growth. Additionally, this field experiment demonstrated
      that at temperatures below 5 degrees C, growth was reduced to rates undetectable
      by the laser diffraction method. The data on mussel shell length show that this
      technique does offer very sensitive and useful comparative measurements of
      physiological function. Measurement of shell growth has the advantage over other
      techniques in that it is non-invasive and non-destructive and thus may be used
      continuously without disturbing critical physiological and biochemical functions;
      however, bivalve physiology is strongly linked to environmental conditions, so it
      is important to include such measures (i.e. seawater temperature and turbidity)
      in the design of the biomonitoring program. Elevated polycyclic aromatic
      hydrocarbon (PAH) levels reflected bioaccumulation in mussels from all the oiled
      mesocosms. This correlated with reduction in growth rate. Maximum reduction in
      growth was observed in mussels from the tilled mesocosm which contained the
      lowest phenanthrene and dibenzothiophene concentrations. The tilling caused an
      increase in suspended solids which inhibited filter feeding activity, and
      resulted in suppressed growth and slower intake of PAH-laden sediment.

PMID- 14669802
TI  - Composting under controlled conditions.
AB  - Three cylindrical reactors, each with a working capacity of approximately 200
      litres, were used to investigate composting. The process was optimised and
      conditions were controlled so that composting on a laboratory-scale thermally
      resembled that occurring in the core of large open heaps. A baseline flow of
      humidified air aerated the reactors in five-minute bursts. The reactors operated
      as closed systems with facilities to analyse the composition of the off-gas for
      ammonia, oxygen and carbon dioxide. Temperature was used to monitor the progress
      of the process. Heat loss from the reactor surface was compensated for with an
      external heat source. A basic model of radial conductive heat losses showed that
      53 watts per square-metre would be the maximum heat flux needed to keep the
      temperature difference across the reactor to within a degree when running at 60
      degrees C. A heating cable was used, which could supply 150 watts per square
      metre, and the radial temperature difference was reduced to within a degree in
      more than 60% of the recorded temperatures in the case studies presented. The
      temperature of the composting material was held at 60 degrees C using a high flow
      rate 'cooling' aeration with temperature feedback. This, however, led to a mean
      vertical temperature difference of at least 10 degrees C. The aeration strategy
      resulted in a well-aerated material, which favoured aerobic microbial activity
      and the temperature increased as a result of the internally generated heat
      associated with composting. Three-quarters of the ammonia was emitted in the
      first week.

PMID- 14669803
TI  - Substrate concentration-independent aerobic granulation in sequential aerobic
      sludge blanket reactor.
AB  - The development of aerobic granules was studied in four column-type sequential
      aerobic sludge blanket reactors fed with different substrate concentrations
      ranging from 500 to 3000 mg l(-1) COD. Results showed that aerobic granules
      successfully formed in all reactors fed with different substrate concentrations,
      indicating that the formation of aerobic granules is independent of the substrate
      concentration. The granule size, roundness, compactness, physical strength, as
      well as cell surface hydrophobicity and cell polysaccharides contents of the
      cultivated aerobic granules were investigated. It was shown that aerobic granules
      formed with different substrate concentrations had similar roundness and
      compactness. However, the size of aerobic granules slightly increased with an
      increase in substrate concentration, while granule strength decreased with
      substrate concentration. It was found that there was a significant increase in
      cell surface hydrophobicity and cell polysaccharides of the aerobic granules
      compared to that of seed sludge. The high cell surface hydrophobicity and high
      cell polysaccharides contents were believed to play an important role in the
      formation of aerobic granules. However, substrate concentration seems not to be a
      governing factor for the formation of aerobic granules. The results of this study
      would be useful for developing aerobic granules-based bioreactor and for better
      understanding of the mechanism of aerobic granulation. It was also clearly
      demonstrated that aerobic granules-based bioreactor would have great potential in
      the treatment of high-strength wastewater.

PMID- 14669804
TI  - Sorption of Cr(VI) and Cu(II) in aqueous solution by ethylenediamine modified
      rice hull.
AB  - The sorption characteristics of Cr(VI) and Cu(II) by ethylenediamine modified
      rice hull from single and binary metal ion solutions were evaluated under various
      experimental conditions. Optimal Cr(VI) and Cu(II) removal from single metal ion
      solutions occurred at pH 2.0 and 5.5, respectively. Simultaneous removal of
      Cr(VI) and Cu(II) occurred at pH greater than 3.0. The sorption kinetics of
      Cr(VI) and Cu(II) from single and binary metal ion solutions were studied with
      reference to metal concentration, agitation rate and particle size. Sorption of
      Cr(VI) was more rapid than Cu(II). The kinetics of metal ion sorption fitted a
      pseudo-second order expression. The variation in the initial uptake rates was
      very small at an agitation rate beyond 150 rpm and sorption was generally
      independent of particle size. Equilibrium sorption data could be fitted into the
      Langmuir isotherm equation. Maximum sorption capacities of ethylenediamine
      modified rice hull for Cr(VI) at pH 2 and Cu(II) at pH 4 in single metal
      solutions were 0.45 and 0.06 mmol g(-1), respectively. This corresponds to an
      enhancement factor of 2.6 and 3 fold for Cr(VI) and Cu(II), respectively,
      compared to natural rice hull. A synergistic effect was observed for sorption of
      these ions in binary metal solutions.

PMID- 14669805
TI  - Characterising vehicle emissions from the burning of biodiesel made from
      vegetable oil.
AB  - Biodiesel manufactured from canola oil was blended with diesel and used as fuel
      in two diesel vehicles. This study aimed to test the emissions of diesel engines
      using blends of 100%, 80%, 60%, 40% , 20% biodiesel and 100% petroleum diesel,
      and characterise the particulate matter and gaseous emissions, with particular
      attention to levels of polycyclic aromatic hydrocarbons (PAHs) which are harmful
      to humans. A real time dust monitor was also used to monitor the continuous dust
      emissions during the entire testing cycle. The ECE(Euro 2) drive cycle was used
      for all emission tests. It was found that the particle concentration was up to
      33% less when the engine burnt 100% biodiesel, compared to 100% diesel. Particle
      emission reduced with increased percentages of biodiesel in the fuel blends.
      Reductions of NOx, HC and CO were limited to about 10% when biodiesel was burned.
      Levels of CO2 emissions from the use of biodiesel and diesel were similar.
      Eighteen EPA priority PAHs were targeted, with only 6 species detected in the
      gaseous phase from the samples. 9 PAHs were detected in particulate phases at
      much lower levels than gaseous PAHs. Some marked reductions were observed for
      less toxic gaseous PAHs such as naphthalene when burning 100% biodiesel, but the
      particulate PAH emissions, which have more implications to adverse health
      effects, were virtually unchanged and did not show a statistically significant
      reduction. These findings are useful to gain an understanding of the emissions
      and environmental impacts of biodiesel.

PMID- 14669806
TI  - Treatment of saline wastewaters from marine-products processing factories by
      activated sludge reactor.
AB  - An activated sludge reactor, operated at room temperature (20-30 degrees C) was
      used to treat saline wastewaters generated by marine-products industries. The
      system was operated continuously and the influence of the organic loading rates
      (OLRs), varying from 250 to 1000 mg COD l(-1) day(-1), on chemical oxygen demand
      (COD) removal was investigated. The system, inoculated with NaCl-acclimated
      culture, removed up to 98% and 88% of the influent COD concentrations at OLRs of
      250 and 1000 mg COD L(-1) day(-1), respectively. Since the organic pollution is
      essentially composed of proteins, microorganisms, which produced proteolytic
      enzymes, were isolated from the activated sludge culture. One bacterium with the
      highest protease activity, identified as Bacillus cereus, was chosen for protease
      production in fishery wastewaters of different concentrations containing combined
      heads and viscera powder. Protease synthesis was strongly enhanced when cells
      were cultivated in two times diluted fishery wastewaters. The enhancement of
      protease synthesis could have been due to the presence in effluent of organic
      matters or salts, which stimulated the growth of the strain and protease
      production.

PMID- 14669807
TI  - Application of advanced oxidation processes for the treatment of cyanide
      containing effluent.
AB  - Batch experiments were carried out for the removal of cyanide in the effluent of
      plating industry by the application of advanced oxidation processes. Four systems
      with different modes of oxidation in combination of ultra violet (UV) light with
      hydrogen peroxide and/or ozone were investigated. Of all the applied systems, UV
      light with two oxidants, i.e. O3 (32 mg min(-1)), and H2O2 (1.36 g l(-1)) was
      found successful in bringing down the amount of cyanide from 157.32 mg l(-1) to
      1.0 mg l(-1), which is the limit set by the Ministry of Environment of Korea for
      cyanide-containing discharges. Other systems, however, could not bring the
      cyanide abatement to the targeted value even with higher dosage of oxidants and
      an extended period of reaction time. Regardless of the oxidation modes applied,
      all the heavy metal ions in the treated effluent were reduced to 90%. Ultra
      violet light with the combination of two oxidants had the economic preference
      over the other systems since a relatively lower dosage of UV-light (2484 W-S cm(
      2)) was found effective at achieving the targeted level of cyanide removal.

PMID- 14669808
TI  - Removal of EDTA by UV-C/hydrogen peroxide.
AB  - Mineralization of a 5 mM EDTA solution at pH 3 was evaluated via TOC removal
      under UV-C irradiation in the presence of H2O2 at various conditions. The highest
      TOC removal (78%) was obtained using a 40:1 H2O2/EDTA molar ratio, after 540 min
      irradiation. However, a 20:1 ratio gave slightly lower results, being
      economically more attractive. Best results of TOC removal were obtained under pH
      controlled conditions. Addition of TiO2 (1 g l(-1)) was detrimental, even in the
      presence of H2O2, indicating that at this concentration, TiO2 inhibits the
      mineralization, probably by scattering or by screening of the light.

PMID- 14669809
TI  - Performance evaluation of leachate treatment system using innovative sulfur
      circulation method.
AB  - A pilot-scale experimental study was carried out to evaluate the performance of
      an innovative method for early stabilization of landfill. This method employs
      sequential processes of: leachate collection; nitrification through aeration;
      sulfate addition in effluent tank; and leachate injection back to the landfill.
      This study focused on: 1) decomposition of recalcitrant organic matters, 2) the
      characteristics of denitrification, 3) sulfide oxidation for sulfate recovery,
      and 4) nitrification by aerating discharged leachate. It was found that, when
      sulfate (SO4(2-)) added leachate was introduced inside the landfill, sulfate
      reducing bacteria decomposed recalcitrant organic matters like lignocellulose by
      using SO4(2-) as an electron acceptor and simultaneously sulfur-oxidizing
      bacteria denitrified the leachate using sulfides (H2S, HS-, S2-) as electron
      donors. These two types of bacteria existed not competitively but symbiotically
      on substrate utilization. Sulfate-reducing bacteria produced S2- while sulfur
      oxidizing bacteria oxidized S2- to SO4(2-). During aeration, the concentration of
      NO3(-)-N increased from near zero up to 925 mg l(-1). Eventual denitrification
      efficiency in the simulated waste landfill was observed to be approximately
      92.3%. Also, S2- present in the discharged leachate was converted to SO4(2-)
      again in the aeration process. Sulfate needed in this process could be
      recirculated. Therefore, the amount of sulfate required in the operation of this
      method could be maintained marginal after the initial addition of sulfate in the
      effluent tank. Decomposition of recalcitrant organic matters and denitrification
      hastened the stabilization of landfill. The results of this study indicated that
      this innovative method was effective and economic.

PMID- 14669810
TI  - The effect of amount of crude oil on extent of its biodegradation in open water-
      and sandy beach-laboratory simulations.
AB  - We examined the biodegradation of varying amounts of artificially weathered
      Alaskan North Slope crude oil in laboratory microcosm test systems that use
      natural seawater and simulate spills in open water and on sandy beaches. The
      model bioremediation treatment consisted of periodic applications of marine
      bacteria, selected to degrade n-alkanes and a range of aromatic compounds,
      suspended in a salts solution that supplied inorganic nitrogen and phosphorous.
      Beach microcosms dosed with low and high oiling lost an average of 22.5% and
      11.3% oil weight, respectively. Open-water microcosms dosed with high and low
      oiling lost 19.1% and 2.9% oil weight, respectively. Thus, the lower doses of oil
      were more efficiently degraded. The model bioremediation treatment also affected
      a greater number of selected analytical endpoints in the lower-oil-dose than
      higher-dose experiments and the former showed more substantial degradation of
      recalcitrant components. Above a certain threshold oil concentration,
      bioremediation did not effectively remove oil. Below this threshold the
      distinction between active bioremediation treatment and intrinsic biodegradation
      of the controls was less prominent; i.e., fewer of the oil components were
      statistically depleted by remediation treatment relative to controls.
      Furthermore, the oil-dose range over which bioremediation was realized in these
      systems occurred at very low oiling levels. Thus, under the environmental
      conditions simulated in these microcosms, the effectiveness of bioremediation
      peaked over a rather narrow low-dose oiling range.

PMID- 14669811
TI  - The mechanisms of Ni2+ ions sorption by AlPO4.
AB  - Sorption of Ni2+ ions by AlPO4 is studied as a function of concentrations and
      temperature at pH 7. Potentiometric titration, dissolution and FTIR studies are
      employed to determine the mechanism of the process of the uptake of Ni2+ ions
      which is found to be both the ion exchange and the surface precipitation of the
      corresponding metal phosphates. Freundlich equation is found applicable to the
      sorption data, and is employed to evaluate the thermodynamic parameters deltaH(o)
      and deltatS(o).

PMID- 14669812
TI  - Effects of temperature on post-methanation of digested dairy cow manure in a farm
      scale biogas production system.
AB  - A post-methanation process that could be adopted at farm-scale, operating at
      temperatures prevailing in farm manure digester post-storage tanks, was
      evaluated. Digested manure samples from a farm digester (35 degrees C) and post
      storage tank (5-10 degrees C) were incubated in parallel batches at 5-20 degrees
      C and as reference at 35 and 55 degrees C. Specific methane yields (kg(-1)
      volatile solids (VS)(added waste)) were 0.20-0.26 m3 at 35-55 degrees C and 0.085
      0.09 m3 at 10-20 degrees C for digester material (345 days of incubation) and
      0.16-0.21 m3 at 35-55 degrees C, 0.053-0.087 kg(-1) VS(added waste) m3 at 15-20
      degrees C and 0.026 m3 at 10 degrees C for post-storage tank material (250 days).
      Both materials produced less than 0.005 m3 at 5 degrees C. However, an increase
      in temperature to 35 degrees C (40 days) improved methane production in assays
      pre-incubated at 5-20 degrees C (9 months). These results suggest that the
      untapped methane potential of the digested manure cannot effectively be recovered
      at temperatures prevailing in farm digested manure storage tanks during the
      winter in Northern latitudes. Nevertheless, as ambient temperatures increase
      during the late spring, an increase in methanogenesis can be expected.

PMID- 14669813
TI  - Use of topical metronidazole in moderate to severe rosacea.
AB  - Rosacea is a chronic condition requiring long-term therapy for control and
      maintenance. Numerous controlled studies have shown that metronidazole 0.75% in
      combination with oral antibiotics significantly reduces the number of papules and
      pustules and erythema severity scores in patients with severe disease. Topical
      metronidazole 0.75% also maintains long-term remissions after oral tetracycline
      has been discontinued. Although original studies involving topical metronidazole
      0.75% used a twice-daily regimen, subsequent work has shown that this formulation
      used once daily is as effective as 1% metronidazole.

PMID- 14669814
TI  - Use of immunosuppressive drugs and lamivudine in a patient with nephrotic
      syndrome, severe renal failure, and HBV cirrhosis: case report.

PMID- 14669815
TI  - Comparative results between two groups of track-and-field athletes with or
      without the use of Master Amino acid Pattern as protein substitute.
AB  - Comparative results of this study have shown that athletes, by taking the Master
      Amino acid Pattern (MAP) as a dietary protein substitute and performing physical
      activity, have had (1) increased body muscle mass, strength, and endurance; (2)
      decreased fat mass; (3) increased basal metabolism rate; (4) greater improvement
      in performance of the nonprevailing muscles compared to the prevailing ones; and
      (5) improved muscular and hematologic lactate clearance, which allows for better
      muscle performance and faster muscle recovery after physical activity. It was
      concluded that the use of MAP as a dietary protein substitute in conjunction with
      physical activity can provide a safe and unprecedented way to optimize the body's
      protein synthesis, thereby improving anthropometric characteristics and physical
      and physiologic performance.

PMID- 14669816
TI  - Results of taking Master Amino acid Pattern as a sole and total substitute of
      dietary proteins in an athlete during a desert crossing.
AB  - Study results show that a 51-year-old female athlete, while taking the Master
      Amino acid Pattern (MAP) as a sole and total substitute for dietary protein, and
      performing physical activity, experienced (1) increased body muscle mass,
      strength, and endurance; (2) decreased body fat mass; (3) greater increase in
      performance of the nonprevailing muscles compared to the prevailing muscles; (4)
      improved cardiorespiratory performance; and (5) increased red blood cells,
      hemoglobin, and hematocrit parameters. It was concluded, confirming previous
      findings, that use of MAP as a sole and total substitute for dietary protein, in
      conjunction with physical activity, provides safer, unprecedented optimization of
      the body's protein synthesis, thereby improving anthropometric characteristics
      and physical and physiologic performance.

PMID- 14669817
TI  - Use of cellulose powder for the treatment of seasonal allergic rhinitis.
AB  - This study was designed to determine whether a unique cellulose powder extract
      could prevent the classic hay fever attack from occurring among volunteers who
      have suffered for some years. Nasaleze enhances nasal mucus, which allows the
      filtration of allergens, to ensure that only clean air reaches the lungs. One
      hundred two volunteers were recruited and, using a simple 5-point scoring system
      to grade their general well-being and severity of any hay fever attacks, the
      overall average score was 3.85, indicating that Nasaleze was able to control hay
      fever very well. Rapid relief of symptoms was also demonstrated, sometimes within
      minutes after inhalation. Overall, 77% of volunteers reported a significant
      reduction in the number of challenges throughout the study period and most graded
      Nasaleze as more effective and reported fewer side effects than with a wide range
      of chemical treatments.

PMID- 14669818
TI  - Essential oils and low-intensity electromagnetic pulses in the treatment of
      androgen-dependent alopecia.
AB  - This double-blind randomized study vs placebo in healthy male and female
      volunteers demonstrates the positive biologic effect on hair loss and hair
      regrowth of a pulsed electromagnetic field in combination with essential oils
      administered according to a regular treatment schedule of 26 weeks. Mean hair
      count comparisons within the groups significantly favor the treatment group,
      which exhibited a decrease in hair loss in 83% of the volunteers and a more than
      20% hair count increase over baseline in 53% of patients. The process exhibited
      no side effects or untoward reactions. The histologic examination correlated with
      the clinical study. A parallel immunohistochemical examination showed an increase
      in the proliferation index, and when the expression of Ki67 (a cell proliferation
      marker) is increased, the mitoses are barely visible in the histologic
      examination. The rationale of this phenomenon is considered to be due to an
      electrophysiologic effect on the quiescent hair follicle.

PMID- 14669819
TI  - GH responses to a near-maximal exercise training session on-the-field in
      cyclists.
AB  - Acute plasma GH response to prolonged (1 h) near-maximal exercise was studied in
      7 elite cyclists (6 males, 1 female; mean age +/- SE: 24.9 +/- 1.4 yr) during a
      routine training session on an uphill track (length: 22.0 km, average slope:
      4.39%) and during a recovery (REC) period of 60 min from the end of exercise. The
      training session entailed a warming-up (WARM) phase of about 20 min at 63% of
      individual maximal heart rate (HRmax) followed by a high intensity exercise (HIE)
      phase of about 60 min at 90-92% of HRmax. GH resting values averaged 0.2 +/- 0.06
      ng/ml; average GH concentration attained a maximal value (21.5 +/- 3.3 ng/ml,
      range: 11.0-38.2 ng/ml) between 20 and 40 min of HIE and significantly decreased
      thereafter (p=0.01), although exercise intensity was unchanged in the following
      period (p=0.14). After WARM, GH concentrations were significantly lower than peak
      values (p=0.05). During REC, GH levels steadily decreased, attaining a value of
      2.6 +/- 0.8 ng/ml 60 min after the end of exercise. It was concluded that during
      prolonged and sustained exercise on-the-field in cyclists, GH value determined at
      the end of the bout may not correspond to the maximal value, which can be
      observed after 20 to 40 min of near-maximal exercise.

PMID- 14669820
TI  - Presence of cortistatin in the human pancreas.
AB  - Cortistatin (CST), a 17-amino acid peptide partially homologous to somatostatin
      (SRIF), has been originally isolated from the cerebral cortex and recently found
      in monocytes and macrophages of the immune system. CST binds all 5 SRIF
      receptors, as well the GH secretagogue (GHS)/ghrelin receptors. CST exerts sleep
      promoting activities, acts on animal motility and behavior and inhibits GH and
      insulin secretion. To investigate the possible occurrence and activities in
      peripheral tissues, expression of CST at the mRNA and peptide level was analyzed
      in the human pancreas by means of RT-PCR, in situ hybridization and
      immunohistochemistry. The specific CST mRNA was found in 3 of 4 pancreatic RNA
      extracts and in the control cerebral cortex. By in situ hybridization, CST mRNA
      was localized in the pancreatic islets, but not in the exocrine pancreas. This
      finding was confirmed by immunostaining with a specific antibody to CST-17 which
      detected CST in single islet cells. These cells also expressed SRIF receptors
      types 2, 3 and 5, ghrelin and GHS receptors. Thus, our findings show the presence
      of CST in the human endocrine pancreas. Local autocrine or paracrine circuits,
      only in part overlapped with those of SRIF, may be active to modulate insulin
      and/or glucagon levels.

PMID- 14669821
TI  - Post-prandial decrease of human plasma ghrelin in the absence of insulin.
AB  - Ghrelin is the most powerful orexigenic hormone in mammalian physiology. Ghrelin
      plasma concentrations increase prior to meal onset, but decrease post-prandially.
      We and others reported previously that insulin reduces circulating ghrelin levels
      and might therefore be a driving force for post-prandial suppression of ghrelin.
      To test the influence of insulin on post-prandial ghrelin regulation, a patient
      with Type I diabetes with complete insulin deficiency received a low glycemic
      index meal and subsequently an additional high glycemic index meal in the absence
      of insulin substitution. Subsequently, a sc injection of 0.08 IU Lispro insulin
      per kg body weight was given. Results were compared to those of a healthy control
      subject matched for sex, age and body mass index, which was undergoing the same
      test series (without Lispro bolus) in the presence of endogenous post-prandial
      insulin secretion. A substantial decrease of plasma ghrelin levels was observed
      in the insulin-deficient patient following low glycemic index carbohydrate load
      (27% plasma ghrelin decrease). The subsequent exposure to a high glycemic index
      meal resulted in a slight additional reduction of ghrelin levels (32% from
      baseline), while Lispro bolus did not induce further changes in circulating
      ghrelin (27% of baseline at termination). This post-prandial response was
      comparable to that of the healthy control subject (33% reduction after the first
      meal, 40% after the second meal). These data tentatively suggest that post
      prandial secretion of ghrelin is not exclusively regulated by plasma insulin or
      plasma glucose but may depend on other metabolic factors yet to be identified.

PMID- 14669822
TI  - Serum paraoxonase 1 activity is decreased in thyroid dysfunction.
AB  - Changes in serum lipid and lipoprotein concentrations occur frequently in
      disorders of thyroid function. LDL-cholesterol (LDL-C) oxidation susceptibility
      is higher in these patients than in normal population. This study aims at
      assessing lipids, lipoproteins, apolipoproteins and serum paraoxonase 1 (PON1)
      activity in patients with thyroid dysfunction. Ninety-nine patients with thyroid
      dysfunction, (49 hypothyroid and 50 hyperthyroid) were compared with 2 separately
      age- and sex-matched control groups. A fasting blood sample was obtained and
      serum total cholesterol, triglycerides, apolipoproteins A-I and B, and PON1
      activity were measured. In hyperthyroid patients, significantly lower PON1
      activity (45 +/- 23 vs 67 +/- 37 IU/ml, p<0.001), triglycerides (112 +/- 53 vs
      166 +/- 130 mg/dl, p<0.05), apolipoprotein A-I (137 +/- 26 vs 154 +/- 21 mg/dl,
      p<0.001) and apolipoprotein B (75 +/- 18 vs 86 +/- 25 mg/dl, p<0.05) were found.
      Hypothyroid patients had lower PON1 activity (46 +/- 21 vs 64 +/- 32 IU/ml,
      p<0.005) compared with controls, and higher total cholesterol (224 +/- 69 vs 185
      +/- 41 mg/dl, p<0.001), LDL-C (133 +/- 59 vs 93 +/- 36 mg/dl, p<0.001), and
      apolipoprotein B (107 +/- 37 vs 84 +/- 23 mg/dl, p<0.001). The results show
      significant changes of lipid levels in thyroid dysfunction. In addition, a
      significant reduction in PON1 activity was observed in both hyper- and
      hypothyroid patients. Increased LDL-C oxidation in thyroid dysfunction observed
      in other studies, at least to some extent, can be attributed to reduced PON1
      activity.

PMID- 14669823
TI  - Is there a therapeutic role for octreotide in patients with ectopic Cushing's
      syndrome?
AB  - Cushing's syndrome (CS) due to ectopic ACTH secretion (EAS) has a high morbidity
      and mortality, because of the underlying tumor and the sequelae of severe
      hypercortisolemia. Therefore, rapid treatment of ectopic CS is mandatory.
      Scintigraphy shows that up to 80% of ectopic ACTH-producing tumors have
      somatostatin receptors. While this suggests that somatostatin analogs may reduce
      ACTH production and treat patients with EAS, the therapeutic role of these agents
      is still evolving. Here we demonstrate the spectrum of responses to octreotide
      therapy in 3 patients with EAS. Diagnostic imaging with the 111In-pentetreotide
      scan did not predict the therapeutic response to octreotide. Two patients with
      positive somatostatin receptor scintigraphy failed to respond to octreotide,
      while one with a negative scan reached eucortisolemia on a maintenance dose of 75
      microg octreotide twice daily or octreotide LAR 30 mg per month. We conclude that
      octreotide is not a first line agent to control hypercortisolemia but may be a
      useful agent when other inhibitors of steroidogenesis fail or parenteral
      administration is required. Before therapy an octreotide challenge test may
      predict therapeutic response. Cortisol levels should be monitored regularly on
      somatostatin analog therapy, because of its unpredictable long-term
      pharmacodynamic profile.

PMID- 14669824
TI  - Prolactin effect on pre-pubertal Sertoli cell proliferation and metabolism.
AB  - Direct effects of PRL on Sertoli cell proliferation were investigated by using
      Sertoli cell primary cultures isolated from both prepubertal rat and porcine
      testes. PRL metabolic effects were analyzed in rat Sertoli cell primary cultures.
      Exposure to physiological doses of PRL resulted in a significant increase (+50
      60%) of basal DNA synthesis, as reflected by the pattern of [3H] thymidine
      incorporation during culture; significant increases in lactate secretion (about
      50%), androgen binding protein (ABP) production (about 30%) and basal protein
      synthesis (25-30%), as reflected in the augmented [14C] valine incorporation,
      were also evident. Taken together, our present findings, indicating significant
      effects of PRL on Sertoli cell proliferation and metabolism, demonstrate that
      Sertoli cells are a potential target for PRL action at testicular level during
      pre-pubertal development.

PMID- 14669825
TI  - Ghrelin secretion in severely obese subjects before and after a 3-week integrated
      body mass reduction program.
AB  - Ghrelin, the endogenous ligand of GH-secretagogue receptors, has been implicated
      in the regulation of feeding behavior and energy balance. Aim of the study was to
      investigate ghrelin levels in fasting conditions and after a standard meal test
      in obese subjects before and after a 3-week integrated body weight reduction
      (BWR) program (consisting of energy-restricted diet, exercise training,
      psychological counselling and nutritional education). Weight, height, fat mass,
      fat free mass (by impedentiometry), circulating ghrelin, insulin and leptin
      levels were evaluated in 10 obese subjects (3 male, 7 female; mean age: 35 +/-
      9.3 yr; body mass index BMI: 45.2 +/- 10.6 kg/m2) before and after weight
      reduction. At baseline, obese subjects showed significantly lower ghrelin levels
      than controls, which were negatively correlated with BMI, weight, insulin and
      leptin levels. Fasting ghrelin levels were not modified by standard meal test in
      obese subjects (from 110.8 +/- 69.7 to 91.8 +/- 70.2 pmol/l p=ns), while a
      significant reduction was observed in controls (from 352.4 +/- 176.7 to 199.0 +/-
      105.2 pmol/l; p<0.01). After a 3-week integrated BWR program obese subjects
      significantly reduced weight, BMI and leptin levels, while no significant changes
      were found both in fasting ghrelin and in ghrelin response after the meal. In
      conclusion, 5% weight loss obtained after a short-term period of integrated BWR
      program is not sufficient to normalize fasting ghrelin levels nor to restore the
      normal ghrelin suppression after a meal in severely obese subjects.

PMID- 14669826
TI  - Intravenous ibandronate in men with osteoporosis: an open pilot study over 2
      years.
AB  - In the treatment of osteoporosis, the tolerance of oral bisphosphonates is often
      low. The high potency of ibandronate allows iv bolus injections that can be
      repeated every 2 to 3 months. However, the best dose and time interval of the
      treatment with iv ibandronate is still debated. Efficacy of 2-mg ibandronate
      injected every 3 months was tested in men with osteoporosis over 2 yr, in a
      prospective, open study. Fourteen men with primary osteoporosis, mean age 57 +/-
      12 yr (range: 40-73), received 2-mg ibandronate iv every 3 months over 2 yr. All
      got 1 g/day calcium and 880 UI/day vitamin D for 2 yr. Bone mineral density (BMD)
      increased after 2 yr by 6.7 +/- 1.5% (mean change +/- SEM) at lumbar spine
      (p<0.001), by 3.2 +/- 08% at trochanter (p<0.001) and by 1.4 +/- 1.1% at femoral
      neck (ns). Serum beta-crosslaps and osteocalcin decreased significantly by 30-45
      and 30%, respectively, during the 2 yr of treatment. Serum calcium increased from
      the lower to the middle tertile of the normal range during the 2 yr of the study.
      The observed decrease of bone remodelling and the increase of BMD are of the same
      magnitude as those described with oral bisphosphonates. The increase of plasma
      calcium confirms the positive effect of the supplementation with calcium and
      vitamin D. These results suggest that 3 months are a good interval between two
      doses of iv ibandronate, when 2 mg are given.

PMID- 14669827
TI  - Acute decrease in circulating T3 levels enhances, but does not normalise, the GH
      response to GHRP-6 plus GHRH in thyrotoxicosis.
AB  - In thyrotoxicosis there is an impaired GH response to GHRH, normal GH
      responsiveness to GHRP-6 and lack of synergistic GH response after simultaneous
      administration of both peptides. We have previously shown that the GHRH-induced
      GH release in these patients increases after an acute reduction of circulating T3
      values with administration of iopanoic acid, a compound that inhibits peripheral
      conversion of T4 to T3. We have now studied the effect of a decrease in serum T3
      levels on the GH response to GHRP-6 (1 microg/kg) plus GHRH (100 microg) in 9
      hyperthyroid patients before and after 15 days of treatment with iopanoic acid (3
      g every 3 days) and propylthiouracil (600 mg/day). Nine normal subjects were also
      studied. In all hyperthyroid patients iopanoic acid induced a rapid decrease and
      normalisation of serum T3 levels. In these subjects peak GH (microg/l; mean +/-
      SE) and AUC (microg/l x 120 min) values after GHRP-6 plus GHRH were significantly
      higher on day 15 compared to pretreatment values (peak, 18.3 +/- 3.0 vs 13.4 +/-
      1.9; AUC, 1227.9 +/- 212.9 vs 968.5 +/- 160.4; p<0.05). Despite the significant
      enhancement of the GH responsiveness to GHRP-6 plus GHRH after treatment with
      iopanoic acid, this response remained significantly blunted when compared to
      controls both in terms of peak GH (18.3 +/- 3.0 vs 83.7 +/- 15.2; p<0.05) and AUC
      values (1227.9 +/- 212.9 vs 4956.5 +/- 889.3; p<0.05). In conclusion, our results
      show that an acute decrease of circulating T3 levels enhances, but does not
      normalise, the GH response to GHRP-6 plus GHRH in thyrotoxicosis. This could
      suggest that circulating T3 does not have a major role in the mechanisms involved
      in the synergistic effect of these peptides.

PMID- 14669828
TI  - Croatia has reached iodine sufficiency.
AB  - This study was performed in 2002, 6 yr after the introduction of a new regulation
      on salt iodination with 25 mg KI/kg of salt. The aim of the study was to evaluate
      whether further significant positive results of improved iodine intake could be
      observed among schoolchildren in Croatia. A total of 927 schoolchildren of both
      sexes, aged 6-12 yr, were included in the study. In Croatia, with a population of
      4,437,460 the research was implemented in four major geographical regions: the
      Northwestern, Slavonia, Northern Adriatic and Dalmatian regions. Investigations
      included randomly selected pupils from regional centers and neighboring smaller
      towns or villages. The results have revealed that thyroid volumes were within the
      normal range according to the provisional WHO/ICCIDD reference values for
      sonographic thyroid volume in iodine-replete school-age children, updated in
      2001. A significant improvement in medians of urinary iodine excretion was
      detected in 2002: from 9 microg/dl in 1991 to 14.6 microg/dl in Zagreb, from 4.3
      microg/dl in 1995 to 13.1 microg/dl in Split, from 9.4 microg/dl in 1997 to 14.2
      microg/dl in Rijeka and from 13.4 microg/dl in 1997 to 14.7 microg/dl in Osijek.
      An overall median of 14.0 microg/dl of urinary iodine excretion was detected in
      Croatian schoolchildren. The control of salt at different levels, from production
      to consumption, including salt produced in all three Croatian salt plants and
      imported salt, revealed that Croatian salt is adequately iodized. From severe
      iodine deficiency before the 1950s, through mild-to-moderate iodine deficiency in
      the 1990s, Croatia has now reached iodine sufficiency.

PMID- 14669829
TI  - Rapid desensitisation of the GH secretagogue (ghrelin) receptor to hexarelin in
      vitro.
AB  - Ghrelin, the recently identified hormone with GH-secreting and appetite-inducing
      effects, acts on the GH secretagogue receptor (GHS-R). GHS-R belongs to the G
      protein-coupled 7 transmembrane domain receptors and activates the phospholipase
      C pathway; it then leads to the release of GH from somatotroph cells via an
      elevation of intracellular calcium concentration. Both in vivo and in vitro
      studies demonstrated that the effect of GH secretagogues (GHS) could be
      desensitised similar to most receptor stimulation systems. We have studied
      whether acute desensitisation of the GHS-R occurs in response to the GHS
      hexarelin in vitro in terms of intracellular calcium concentration. Chinese
      hamster ovary cells were transiently transfected with cDNA encoding the human
      type 1a GHS-R. The presence of messenger RNA was confirmed with RT-PCR, while no
      GHS-R was observed in mock-transfected cells. Calcium responses to the peptide
      GHS analogue hexarelin were measured using the fluorescent indicator fura-2.
      Cells were stimulated with the peptide GHS, hexarelin, at concentrations between
      10(-10) and 10(-7) M. Cells transfected with the GHS-R cDNA demonstrated a
      significant and specific calcium response to hexarelin that was not observed in
      mock-transfected cells. Marked desensitisation of the calcium response to
      hexarelin was observed 2-5 min after the first dose of hexarelin (10(-7) M) was
      administered. These data show directly for the first time the desensitisation of
      the GHS receptor signal at the second messenger level. The desensitisation of the
      receptor may play a major role in the regulation of effect of circulating or
      locally produced ghrelin both in the GH and in the appetite-regulating system or
      in other systems where ghrelin has been shown to be active, such as the
      cardiovascular system or cell proliferation.

PMID- 14669831
TI  - Acute sterile meningitis as a primary manifestation of pituitary apoplexy.
AB  - Pituitary apoplexy is a rare and underdiagnosed clinical syndrome. It results
      from hemorrhagic infarction of the pituitary gland. In its classical form it is
      characterized by acute headache, ophthalmoplegia, visual loss and pituitary
      insufficiency. Meningeal irritation signs, clinically indistinguishable from
      infectious meningitis, are considered rare and have not been reported as
      presenting signs. We report a 53-yr-old man who was admitted to hospital
      following acute headache, fever, neck stiffness and paresis of the left
      oculomotor and abducent nerves. A lumbar puncture revealed an increased number of
      polymorphs but with a sterile cerebral spinal fluid. Magnetic resonance imaging
      (MRI) showed an intrasellar mass with central necrosis in an enlarged sella.
      Endocrinological evaluation demonstrated insufficient thyroid, adrenocortical,
      and gonadal function. Necrosis within a chromophobe adenoma was found upon
      surgical decompression of the sella. After surgery anterior panhypopituitarism
      did not recover, while ophthalmoplegia subsided. The patient is now in good
      health under appropriate hormonal replacement therapy.

PMID- 14669830
TI  - Effects of a short-term calcium and vitamin D treatment on serum cytokines, bone
      markers, insulin and lipid concentrations in healthy post-menopausal women.
AB  - In vitro studies have shown that 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] decreases
      cytokine production by monocytes and lymphocytes. In addition, intravenous or
      oral pulse calcitriol treatment suppresses interleukin 6 (IL6) and
      interleukin1beta (IL1beta) in hemodialysis patients. We studied the effect of a
      daily 12-week course of 1000 mg calcium and 800 U cholecalciferol on circulating
      25 hydroxyvitamin D [25(OH)D], PTH, cytokines, osteoprotegerin (OPG), C-reactive
      protein (CRP), bone markers, lipid parameters and insulin levels in 47 healthy
      post-menopausal women. Thirty-nine women completed the study. A significant
      increase in 25(OH)D and a significant decrease in PTH were observed (p=0.0043 and
      p<0.0001, respectively). In addition, alkaline phosphatase, osteocalcin and, to a
      lesser extent, urinary free deoxypiridinoline (DPD) decreased significantly
      (p<0.0001, p=0.0002 and p=0.026, respectively). No change in circulating IL6,
      tumor necrosis factor alpha (TNFalpha), CRP, OPG, triglycerides, LDL- and HDL
      cholesterol, and insulin levels was observed. Correlation studies in the 47 women
      enrolled in the study revealed inverse significant correlations between OPG on
      one side and body mass index, LDL-cholesterol, IL6, CRP and insulin levels on the
      other (p=0.002, p=0.002, p=0.004, p=0.023 and p=0.0001). Also, IL6 was
      significantly correlated with insulin levels (p=0.0005). In a multivariate model,
      both insulin and LDL-cholesterol were independently associated with OPG, while
      only insulin was independently associated with IL6. Our results showed no effect
      of a short-term calcium-vitamin D treatment on circulating cytokines, CRP,
      insulin levels and lipid parameters. This could be related to the low circulating
      cytokine concentrations in healthy subjects or to the short duration of
      treatment. The interesting association we found between OPG and some
      cardiovascular risk markers deserves further investigation.

PMID- 14669832
TI  - Proinsulin-secreting neuroendocrine tumor of the pancreas.
AB  - Insulinoma is characterized by spontaneous fasting hypoglycemia. Diagnosis relies
      on inappropriately increased insulin levels (>6 microU/ml), high insulin/glucose
      ratio (IGR >0.3), raised proinsulin values (>5 pMol/l). A 74-yr-old man was
      referred to us for episodes of symptomatic hypoglycemia without hyperinsulinemia
      and imaging [abdominal computed tomography (CT) and magnetic resonance scans]
      negative for neuroendocrine tumor (NET). During hospitalization severe
      hypoglycemic crises persisted requiring continuous glucose iv infusion. Insulin
      values (immunofluorimetric method) were not inappropriately increased,
      accordingly IGR was normal but C-peptide was in the upper-normal range.
      Proinsulin levels measured with specific radioimmunoassay were remarkably high.
      Octreoscan study was negative whereas endoscopic ultrasound disclosed a 10 mm
      lesion in the body of the pancreas, confirmed by rapid spiral CT scanning with
      dynamic images. Increased proinsulin levels allowed diagnosis of a secreting NET.
      After removal of the lesion, the patient experienced hyperglycemia. Histology
      confirmed a benign NET positively staining for insulin. In conclusion, proinsulin
      assay is of particular help when immunoreactive insulin, measured by specific new
      immunometric assays (immunoenzymometric and immunofluorimetric assays), is
      normal. These methods have good precision and specificity (no cross reactivity
      with intact or Des 31,32 proinsulin), but rare insulinomas secreting most, or
      all, of their insulin-like activity as proinsulins would go undetected if insulin
      levels alone were measured.

PMID- 14669834
TI  - Somatostatin and thyroid.

PMID- 14669833
TI  - Bilateral osteonecrosis of the femoral head in an adult man affected by
      congenital estrogen deficiency.
AB  - Osteonecrosis of femoral head is related to different predisposing factors. The
      pathogenesis is not completely understood, but an ischemic impairment seems to be
      one of the major determinants of bone necrosis. The association of bilateral
      necrosis of femoral heads and congenital aromatase deficiency is here reported.
      The absence of estrogen activity, as well as the persistence of unfused epiphyses
      for a long period of life, may be involved in the determinism of bilateral
      necrosis of bone femoral heads. The possibility of development of bone necrosis
      in patients affected by congenital estrogen deficiency needs to be considered and
      magnetic resonance imaging can be a useful method for an early detection of this
      disease.

PMID- 14669835
TI  - Androgens and vascular function.

PMID- 14669836
TI  - Resistance to thyrotropin.
AB  - Resistance to TSH is a syndrome of reduced sensitivity to a biologically active
      TSH molecule. Subjects have elevated TSH levels but no goiter. However, thyroid
      hormone concentration may vary from normal to very high, depending on the
      severity of the resistance. Individuals with very high TSH, low T4 and
      hypoplastic thyroid glands can be mistakenly diagnosed as having primary
      hypothyroidism due to a defective development of the thyroid gland. Those with
      normal or slightly decreased T4 can be misdiagnosed as having central
      hypothyroidism especially if their serum TSH concentration is only slightly
      elevated. Mutations in the TSH receptor (TSHr) gene have been reported in 16
      families with homozygous or compound heterozygous inheritance. The mutant TSHrs
      show reduced or no function due to either altered ligand binding or defect in
      membrane targeting. Some individuals, heretozygous for a TSHr gene mutation can
      present mild resistance to TSH manifesting as euthyroidism with slight
      hyperthyrotropinemia. A larger proportion of families express the phenotype of
      resistance to TSH in the absence of a TSHr defect. In many the inheritance is
      dominant and the genetic cause has not been yet determined.

PMID- 14669837
TI  - Germline and somatic thyroid hormone receptor mutations in man.
AB  - Thyroid hormone plays important roles in metabolism, growth, and differentiation.
      Germline mutations in thyroid hormone receptor beta (TRbeta) have been identified
      in many individuals with resistance to thyroid hormone (RTH), a syndrome of
      hyposensitivity to T3. However, it has become increasingly apparent that somatic
      mutations can also occur in individual tissues, and are associated with tumors
      and malignancies in man. Herein we review the occurrence and identification of
      germline and somatic TR mutations and characterization of their pathological
      effects on hormone resistance and tumorigenesis.

PMID- 14669839
TI  - Alternatives for optimal hormone replacement therapy.
AB  - To satisfy the needs of women with a wide variety of different medical histories
      and preferences, a wide choice of various forms of hormone replacement therapy
      (HRT) is desirable. The potential long-term benefits of HRT, in terms of
      osteoporosis, cardiovascular disease and dementia, require good compliance, which
      in turn requires an HRT formulation that is highly acceptable. An absence of
      weight gain and lack of androgenic effects are of great importance, as are
      predictable bleeding and positive effects on postmenopausal symptoms and quality
      of life. HRT should be tailored to each woman's needs by the choice of
      appropriate estrogens and particularly a progestogen with a suitable
      pharmacological profile. An ideal progestogen should be targeted at preventing
      endometrial hyperplasia without opposing the effects of estrogen on the vessels.
      Several new progestogens have been synthesized in recent years. Dienogest, the
      progestogenic component of a new hormone replacement therapy with estradiol
      valerate, has many desirable features, including antiandrogenic properties; in
      this respect, it is unique amongst progestogens derived from testosterone.
      Tailored HRT should treat symptoms, minimize risk factors, meet personal
      preferences and lifestyle needs, and not be contraindicated for concomitant
      diseases. During the next decade, optimal HRT must match a number of trends,
      including an aging population, and is likely to be influenced by the outcome of
      major trials such as the Women's Health Initiative trial whose negative results
      will impact the prescriptions, the advent of new compounds--particularly the
      selective estrogen receptor modulators and progestogen receptor modulators--and
      the introduction of new methods of delivery, including vaginal rings and
      medicated intrauterine systems.

PMID- 14669838
TI  - Aldosterone receptor antagonists: biology and novel therapeutical applications.
AB  - Recent studies suggest that a dysregulation of the aldosterone system is involved
      in the pathophysiology of different cardiovascular diseases, including myocardial
      failure and several cases of essential hypertension. In both rat models and in
      humans, aldosterone action has been shown to induce heart remodeling and
      interstitial and perivascular fibrosis of the myocardium. For these reasons, a
      rationale for the use of aldosterone antagonists (ARAs) of the spirolactone
      family, which have been available for decades in the treatment of aldosterone
      excess syndromes, has now emerged. Moreover, the recent validation of their use,
      in combination with the current therapy, for the treatment of these
      cardiovascular diseases by trials like the RALES Study has further strenghtened
      this approach. The development of compounds, like eplerenone, with a greater
      selectivity for mineralocorticoid receptors, seems promising also in terms of
      reduction of endocrine side effects. The addition of aldosterone antagonists to
      the conventional therapy of myocardial failure and of selected cases of
      hypertension thus appears beneficial, resulting in an improved survival rate and
      a reduced incidence of cardiac complications. This review article, after a brief
      recall of the physiology of the aldosterone system, addresses the emerging role
      of aldosterone in cardiovascular diseases, considers the pharmacology of ARAs and
      the novel therapeutical applications of these compounds in hypertension and heart
      failure.

PMID- 14669840
TI  - Pharmacology of estradiol valerate/dienogest.
AB  - The particular features of the pharmacology of a new continuous regimen for
      hormone replacement therapy containing 2 mg estradiol valerate (E2V) and 2 mg
      dienogest (DNG) (Climodien, Schering AG, Berlin, Germany) depend largely on its
      progestogenic component. Dienogest has the essential properties of an effective
      progestogen, so that it protects against endometrial proliferation and remarkably
      does not counteract the effects of estrogens. It is a derivative of 19
      nortestosterone, but, instead of having an alkyl group at position C17, it has a
      cyanomethyl group, which endows it with a unique pharmaceutical profile. Its
      pharmacokinetics make it suitable for oral administration, without accumulation
      following repeat dosing. The strength of its effect on the endometrium is
      reflected by the fact that its progestogenic potency (ovulation
      dose/transformation dose) is about four times greater than that of any other
      progestogen. It does not bind to sex hormone binding globulin (SHBG), a feature
      that helps to keep free serum levels of dienogest high and free testosterone
      levels low. The low antiestrogenicity of dienogest has been well demonstrated in
      studies of estrogen-related parameters, such as SHBG levels and vasodilatation
      markers (cyclic guanosine monophosphate, 5-hydroxylindole acetic acid). Receptor
      binding studies show similar antiandrogenic effects for dienogest and cyproterone
      acetate, although the Hershberger test of clinical androgenicity suggests that
      dienogest is not as strongly antiandrogenic as cyproterone acetate, but is more
      antiandrogenic than chlormadinone acetate or drospirenone. In summary, E2V/DNG is
      well suited as an effective hormone replacement therapy, with the potential for
      good bleeding patterns and low androgenicity, owing to its formulation with a
      progestogenic component that is highly endometriotropic, has low
      antiestrogenicity and exhibits considerable antiandrogenicity.

PMID- 14669841
TI  - Clinical efficacy and safety of combined estradiol valerate and dienogest: a new
      no-bleed treatment.
AB  - A combination of 2 mg estradiol valerate with 2 mg dienogest (E2V/DNG)
      (Climodien, Schering AG, Berlin, Gemany) is the first continuous combined
      postmenopausal hormone replacement therapy (HRT) preparation to contain a
      progestogen with substantial antiandrogenic activity. A study of its clinical
      efficacy and safety in a comparative study versus a combination of 2 mg estradiol
      with 1 mg norethisterone acetate (E2/NETA) has shown both preparations to be
      highly effective in achieving a rapid response in women with postmenopausal
      symptoms, in terms of hot flushes and the Kupperman index. Biopsy and ultrasound
      studies have demonstrated that E2V/DNG quickly and effectively achieved
      endometrial atrophy in the vast majority of subjects, suggesting a protective
      role in endometrial proliferation. Data on PP-14 (glycodelin) levels may indicate
      that E2V/DNG is even more effective than E2/NETA in maintaining endometrial
      atrophy. No-bleed rates with E2V/DNG at 1, 6 and 12 months were at least as
      favorable as those with other standard HRT products, with evidence that the no
      bleed state is attained more quickly with E2V/DNG. The proportions of women with
      the no-bleed state in a large-scale study (n = 1501) at 1, 6 and 12 months were
      71.8%, 76.6% and 86.4%, respectively. Women with irregular bleeding before
      treatment responded to E2V/DNG in a manner similar to those without bleeding;
      this concordance was especially marked after five cycles of treatment. In the
      comparative study, the mean number of days of bleeding over 12 cycles was
      significantly lower for E2V/DNG than for E2/NETA. Overall, the profiles of
      adverse events recorded in clinical use were similar in the two preparations,
      whilst the safety profile of E2V/DNG in the large-scale study was similar to that
      of other HRT preparations and gave no cause for clinical concern. The 2 mg E2V/2
      mg DNG preparation was associated with a favorable lipid profile, whilst a
      similar combination (2 mg E2V/3 mg DNG) showed no impact on carbohydrate
      metabolism or hemostasis, compared to placebo. In summary, 2 mg E2V/2 mg DNG is a
      novel continuous combined HRT preparation that is effective in treating
      postmenopausal symptoms rapidly, and has a highly favorable bleeding profile.
      Studies of the safety of 2 mg E2V/2 mg DNG in clinical use have uncovered no
      factors likely to be disadvantagous in comparison with other HRT products in
      widespread use.

PMID- 14669842
TI  - Menopause, mood and management.
AB  - Although the short-term and long-term clinical benefits of hormone replacement
      therapy (HRT) are well documented, there is a growing revival of interest in
      psychosocial and holistic approaches to the menopause and its treatment. The
      menopause occurs at a time of life when women are facing many threats and
      challenges, and it is important not to identify the menopause erroneously as the
      sole reason for reductions in the quality of life of such individuals. Most women
      attending a menopause clinic complain of psychological symptoms such as mood
      swings, rather than purely physical symptoms, and it is likely that the
      physiological correlates of such psychological symptoms have been underestimated.
      Much of the distress experienced by menopausal women is also linked to their
      beliefs and perceptions relating to the processes that they are experiencing, and
      to misinformation and myths with which they may be burdened. An awareness of this
      complex scenario by clinicians helps them to treat their patients more
      effectively and to prescribe appropriate HRT on an individual patient basis.

PMID- 14669844
TI  - How we do it: virtual bronchoscopy.

PMID- 14669843
TI  - Sleep, vigilance and cognition in postmenopausal women: placebo-controlled
      studies with 2 mg estradiol valerate, with and without 3 mg dienogest.
AB  - OBJECTIVE: To determine the effects in postmenopausal women with insomnia of
      hormone replacement therapy (HRT) with 2 mg estradiol valerate (E2V) alone, or in
      combination with 3 mg dienogest (DNG), in the context of the introduction of the
      novel preparation Climodien (2 mg E2V/2 mg DNG) (Schering AG, Berlin, Germany).
      METHODS: Parallel groups of women with insomnia related to the postmenopausal
      syndrome were randomized to 2 months' treatment with 2 mg E2V, 2 mg E2V/3 mg DNG
      or placebo (respectively, n = 17, 16, 16). Patients were then studied with
      techniques for assessing sleep quality, vigilance and cognition. Sleep quality
      was determined subjectively by means of the questionnaire-based sleep and
      awakening quality scale (SSA), and objectively with polysomnography. Sleep
      related breathing disorders were evaluated by means of the apnea/hypopnea index.
      Vigilance was measured using quantitative electroencephalography with statistical
      probability mapping. Cognition (speed of information processing, cognition
      processing capacity and perceptual processing resources) was studied using the
      techniques of auditory event-related potentials (P300 latency and amplitude).
      RESULTS AND CONCLUSIONS: Treatment with 2 mg E2V and 2 mg E2V/3 mg DNG
      significantly improved subjective sleep quality and showed trends towards
      improvements in objective sleep quality. The combination of 2 mg E2V/3 mg DNG
      also improved the apnea/hypopnea index. Vigilance was slightly improved by
      treatment with 2 mg E2V and markedly with 2 mg E2V/3 mg DNG. Speed of information
      processing was improved with 2 mg EV2 and 2 mg E2V/3 mg DNG, whilst the latter
      also improved cognitive processing capacity and perceptual processing resources.
      The study provides evidence that HRT can improve sleep quality and mental
      functioning in postmenopausal women and that E2V/DNG combinations, such as 2 mg
      E2V/2 mg DNG, should be considered for this indication and also for the treatment
      of sleep-related breathing disorders in the menopause. The addition of dienogest
      to estradiol valerate did not antagonize the benefits of estradiol valerate in
      terms of sleep quality but rather potentiated estradiol valerate-related
      improvements in vigilance and some aspects of cognition.

PMID- 14669845
TI  - Case of the month. Schwannoma of the vagus nerve.

PMID- 14669846
TI  - Paranasal and orbital anatomy revisited: identification of the ethmoid arteries
      on coronal CT scans.
AB  - OBJECTIVE: The aim of this study was to identify recognizable landmarks on
      coronal CT (CCT) scans for the localization of the anterior and posterior ethmoid
      arteries, which are important anatomic structures and surgical landmarks within
      the ethmoid sinuses. MATERIALS AND METHODS: Four series of plastinated cadaver
      specimens and 80 CCT examinations were evaluated to identify the anatomical
      landmarks that define the course of the anterior and posterior ethmoid arteries
      within the ethmoid sinuses. RESULTS: The following anatomic landmarks: the
      indentations into the medial orbital wall, the relationship between the superior
      oblique and medial rectus orbital muscles, and the lateral ethmoid fovea wall
      thinning proved to be useful CCT landmarks for the localization of the anterior
      and posterior ethmoid arteries. CONCLUSION: The results of this study suggest
      that familiarity with the above-mentioned landmarks on routine CCT images
      facilitates the localization of the anterior and posterior ethmoid arteries as
      they enter the ethmoid sinus.

PMID- 14669847
TI  - 3D CT angiography of the kidney.

PMID- 14669848
TI  - ATP-dependent K+ channels in renal ischemia reperfusion injury.
AB  - ATP-dependent K+ channels (KATP) account for most of the recycling of K+ which
      enters the proximal tubules cell via Na, K-ATPase. In the mitochondrial membrane,
      opening of these channels preserves mitochondrial viability and matrix volume
      during ischemia. We examined KATP channel modulation in renal ischemia
      reperfusion injury (IRI), using an isolated perfused rat kidney (IPRK) model, in
      control, IRI, IRI+200 microM diazoxide (a KATP opener), IRI + 10 microM
      glibenclamide (a KATP blocker) and IRI + 200 microM diazoxide + 10 microM
      glibenclamide groups. IRI was induced by 2 periods of warm ischemia, followed by
      45 min of reperfusion. IRI significantly decreased glomerular filtration rate
      (GFR) and increased fractional excretion of sodium (FENa) (p < 0.01). Neither
      diazoxide nor glibenclamide had an effect on control kidney function other than
      an increase in renal vascular resistance produced by glibenclamide. Pretreatment
      with 200 microM diazoxide reduced the postischemic increase in FENa (p < 0.05).
      Adding 10 microM glibenclamide inhibited the diazoxide effect on postischemic
      FENa (p < 0.01). Histology showed that kidneys pretreated with glibenclamide
      demonstrated an increase in injury in the thick ascending limb of outer medulla
      (p < 0.05). Glibenclamide significantly decreased post ischemic renal vascular
      resistance (p < 0.05), but had no significant effect on other renal function
      parameters. Our results suggest that sodium reabsorption is improved by KATP
      activation and blockade of KATP channels during IRI has an injury enhancing
      effect on renal epithelial function and histology. This may be mediated through
      KATP modulation in cell and/or mitochondrial inner membrane.

PMID- 14669849
TI  - Effect of nitric oxide synthase inhibition and saline administration on blood
      pressure and renal sodium handling during experimental sepsis in rats.
AB  - Much effort has been made in recent years to clarify metabolic and renal function
      changes in sepsis. A number of studies performed in different models of sepsis
      have been described. One such model that is frequently used is cecal ligation and
      puncture (CLP) in rats. This model resembles human sepsis in several important
      aspects, such as an early phase of hyperdynamic, hypermetabolic sepsis followed
      by a late hypodynamic, hypometabolic phase. The present study evaluated the blood
      pressure (n = 5) and renal function changes during development of CLP renal
      failure and to determine the effects of NOS inhibition (L-NAME) and 0.15 M NaCl
      administration on tail blood pressure and renal function in randomly assigned
      five groups (n = 10 each): (1) Sham-operated, (2) Sham-operated L-NAME-treated,
      (3) CLP rats, (4) CLP L-NAME-treated, and (5) CLP 0.15 M NaCl-treated rats. The
      basal tail blood pressure was not significantly different among the four groups.
      One week later, arterial pressure was significantly increased in sham-operated L
      NAME-treated rats (159 +/- 12 mmHg) compare with the other groups (118 +/- 9.0
      mmHg in nontreated rats, p < 0.05). Blood pressure shows a slightly and not
      significant decrease up to 12h in L-NAME and 0.15 M NaCl treated rats, which in
      turn was followed by a significant reduced arterial pressure 18h after CLP in
      both groups (L-NAME: 96.0 +/- 3.6 mmHg, p < 0.05) and NaCl: 82.3 +/- 2.4 mmHg, p
      < 0.05) compared to sham-operated groups. The glomerular filtration rate
      estimated by CCr decreases significantly in the CLP untreated group (p < 0.001)
      and did not significantly differ from the sham-operated and L-NAME-treated groups
      (p = 0.4) during the studies of renal tubule sodium handling. On the other hand,
      subcutaneous 0.15 M NaCl administration prevented CCr decreases in CLP rats (p =
      0.25). CLP increased the FENa in the sham-operated from: 857.2 +/- 85.1
      delta%min(-1) to CLP: 1197.8 +/- 119.0 delta%min(-1). The high FENa to CLP was
      blunted and significantly reduced by previous systemic treatment of animals with
      L-NAME from sham-operated+L-NAME: 1368.0 +/- 72.0 delta%min(-1) to CLP+L-NAME:
      1148.0 +/- 60.4 delta%min(-1) (p < 0.01). The enhanced FENa in the CLP group were
      accompanied by a significant increase in proximal sodium reabsorption rejection.
      The salient findings of the present study suggest that a decrease in the blood
      pressure and creatinine clearance caused by CLP may benefit from L-NAM and fluid
      resuscitation during initial bacteremia (first 12 h) by promoting an additional
      increase of tubule sodium reabsorption in the post-proximal segments of nephrons,
      but these therapies could not prevent acute renal failure after established
      endotoxemia.

PMID- 14669850
TI  - Beneficial effect of pentoxifylline on cisplatin-induced acute renal failure in
      rabbits.
AB  - Pentoxifylline (PTX) has been reported to inhibit TNF-alpha production and
      prevent several types of acute renal failure. This study was undertaken to
      determine the effect of PTX on the cisplatin-induced acute renal failure in
      rabbits. Rabbits received a single injection of cisplatin (5 mg/kg, i.p.) with or
      without PTX pretreatment (30 mg/kg, i.v.). Alterations in renal function,
      apoptotic cell death, and TNF-alpha mRNA expression were measured at 24 or 48 h
      after cisplatin injection. Cisplatin caused an increase in BUN and serum
      creatinine levels, a reduction in GFR, and an increase in fractional Na+
      excretion. Such changes were significantly attenuated by PTX pretreatment (30
      mg/kg, i.p.) 30 min before and 24 h after cisplatin injection. Morphological
      evaluation showed that cisplatin injection induced diffuse proximal tubular
      necrosis and the effect was reduced by PTX pretreatment. Cisplatin induced
      apoptotic cell death in renal cortex and the effect was significantly prevented
      by PTX. Treatment of opossum kidney cells with cisplatin resulted in cell death,
      which was significantly prevented by PTX. The increase in lipid peroxidation and
      the decrease in renal blood flow induced by cisplatin were not affected by PTX.
      The expression of TNF-alpha mRNA was increased after cisplatin injection and the
      effect was inhibited by PTX pretreatment. These results suggest that cisplatin
      induced acute renal failure in rabbits is associated with an induction of TNF
      alpha-mediated apoptosis, and that PTX may exert a protective effect against
      cisplatin nephrotoxicity by inhibiting TNF-alpha production.

PMID- 14669851
TI  - Study of serum and tissues angiotensin converting enzyme (ACE) activity in rat
      with gentamicin induced renal toxicity.
AB  - PURPOSE: In this research ACE activity (as a marker of epithelial injury) was
      studied in rats with gentamicin induced renal toxicity. METHODS: Male Sprague
      Dawley rats were sacrificed 1, 3, 5, and 7 days after gentamicin injection, 100
      mg/kg/day for 1, 3, 5, and 7 consecutive days. ACE activity was measured in
      serum, kidney and lung. These data were compared with normal saline-treated rats.
      Histological scoring of renal cortical pathology was performed on days 1, 3, 5,
      and 7. RESULTS: Treatment of rats with gentamicin resulted in renal damage
      evidenced by proteinuria, polyuria, and decreased creatinine clearance. The
      damage to the kidney proximal tubule was evident by (a) the histological analysis
      at light microscopy and (b) the augmentation in the urinary excretion of N-acetyl
      beta-D-glucosaminidase (NAG). Kidney ACE activity decreased while lung and serum
      ACE activity didn't change until day 7. Lung ACE activity increased significantly
      on day 7. Kidney and serum ACE activity increased too. Blood pressure increased
      significantly on day 7. This corresponded well with the lung ACE activity
      increment. CONCLUSION: These data suggest that kidney ACE activity decreased
      significantly just one day after gentamicin administration and prior to kidney
      NAG decrease.

PMID- 14669852
TI  - Evaluation of two protocols of uremic rat model: partial nephrectomy and
      infarction.
AB  - Animal models of chronic renal failure have been mostly achieved by partial
      ablation of renal parenchyma, the two most common techniques employed being
      surgical resection or infarction. Evaluation of the uremic model using these two
      techniques was carried out in Wistar rats. Two weeks after operative procedure,
      measured serum urea levels in the resection and infarction models were 59.1 and
      64.3 mg/dL (normal range 15.6-24.4 mg/dL) respectively. However, the standard
      deviation in the former was significantly lower, 6.3 vs. 97.1 mg/dL from
      infarction model, p = 0.007. A consistent degree of glomerular filtration rate
      reduction was obtained in the resection model, resulting in 20-30% of normal
      creatinine clearance. This compared favorably with the creatinine clearance range
      (0.3-74% of normal) from the infarction model, in which two animals died of
      uremia and seven had higher than 50% of normal creatinine clearance. It is
      reasonable to attribute reproducibility and homogeneity demonstrated in the
      resection model to (i) more precise control of renal ablation extent with
      surgical techniques and (ii) less interplay of confounding injury mechanism to
      remnant kidney. These data support superiority of the resection model as an
      experimental tool for pathophysiological and/or interventional investigations of
      chronic renal failure.

PMID- 14669853
TI  - Ultrafiltration volume is associated with changes in blood pressure in
      chronically hemodialyzed patients.
AB  - INTRODUCTION: Volume overload is a main factor in development of hypertension in
      hemodialysis patients. In order to demonstrate impact of ultrafiltration volume
      on blood pressure during 15-months period in a group of patients undergoing
      chronic hemodialysis therapy, we conducted this study. We hypothesized that
      ultrafiltration volume different affects the pre/postdialysis systolic pressure,
      diastolic pressure, mean arterial pressure (MAP), and pulse pressure (PP) values.
      SUBJECTS AND METHODS: Study subjects were 23 anuric chronically hemodialyzed
      patients. The overall study time was 15 months, and 136 single hemodialysis
      treatments were analyzed. RESULTS: Ultrafiltration was negatively correlated with
      predialysis systolic blood pressure (r = -0.169, p = 0.025), postdialysis
      systolic blood pressure (r = -0.292, p < 0.001), postdialysis MAP (r = -0.186, p
      = 0.015), predialysis PP (r = -0.290, p < 0.001), and postdialysis PP (r = 
      0.370, p < 0.001). Ultrafiltration/dry body mass (UF/W) ratio was negatively
      correlated with predialysis PP (r = -0.222, p = 0.005), postdialysis PP (r = 
      0.340, p < 0.001), and postdialysis systolic blood pressure (r = -0.243, p =
      0.002). We found significant difference in postdialysis PP between dialyses with
      UF/W ratio < or = 0.05 an dialyses with UF/W ratio > 0.05 (63.49 +/- 20.76 vs.
      56.27 +/- 16.33 mmHg, p = 0.033). CONCLUSION: The ultrafiltration volume strongly
      affects postdialysis PP values. Evaluation of elevated blood pressure treatment
      in patients undergoing chronic hemodialysis therapy must be considered in respect
      of postdialysis PP values, not just depending on pre/postdialysis systolic and
      diastolic pressur or MAP values.

PMID- 14669854
TI  - Correlation of serum leptin concentrations with body composition and gender in
      Taiwanese hemodialysis patients without diabetes.
AB  - OBJECTIVE: (1) To evaluate the impact of body composition and gender on serum
      leptin concentration in hemodialysis patients. (2) To study which marker of
      adiposity is most appropriate in Taiwanese hemodialysis patients without
      diabetes. (3) To compare the nutrition status between nonlean and lean subjects.
      PATIENTS AND METHODS: Serum leptin concentrations were measured by
      radioimmunoassay collected in 88 hemodialysis patients without diabetes.
      Bioimpedance analysis was performed to determine percent fat mass (%FM), lean
      body mass (LM), and total body water (TBW). Body mass index (BMI) was calculated
      as weight/height2. Albumin and transferrin were measured by standard laboratory
      methods. RESULTS: Serum leptin levels were more correlated with percent fat mass
      (r = 0.697; P < 0.001) than with body fat mass (r = 0.672; P < 0.001) or with BMI
      (r = 0.594; P < 0.001) in the group as a whole and in each subgroup when analyzed
      separately by gender. The mean (+/- SD) serum leptin levels were 32.5 +/- 34.3 ng
      mL(-1) in women subjects and 13.6 +/- 15.5 ng mL(-1) in men subjects (P < 0.001).
      Multiple regression analysis in all subjects revealed that serum leptin levels
      were independently affected by percent fat mass and gender. Adiposity corrected
      serum leptin, such as leptin/BMI, leptin/percent fat mass, and leptin/body fat
      mass was significantly different between sexes (P < 0.001). The significantly
      higher serum leptin concentrations in women than in men were observed in obese
      subjects with BMI > 25 kg/m2 (P < 0.001) as well as nonobese subjects with BMI <
      25 kg/m2 (P < 0.05). There were no differences in lean mass and albumin between
      nonlean and lean subjects. CONCLUSION: Gender and adiposity had impact on serum
      leptin levels in hemodialysis patients without diabetes. In terms of adiposity,
      serum leptin levels had stronger correlation with percent fat mass than with body
      fat mass (FM) or BMI in Taiwanese hemodialysis patients. Steady-state serum
      leptin levels could serve as valuable clinical markers for the body adiposity in
      stable hemodialysis patients without diabetes. Protein malnutrition markers and
      lean mass should be checked in lean subjects for the evaluation of the protein
      stores of hemodialysis patients.

PMID- 14669855
TI  - Role of vascular access as a risk factor for infections in hemodialysis.
AB  - Infections are a major cause of morbidity and mortality in chronic hemodialysis
      patients. This single center prospective study was carried out to determine the
      incidence and risk factors for infection in hemodialysis patients and plan
      appropriate strategies to reduce the risk of infection. A total of 84 consecutive
      patients who were initiated on hemodialysis over a 2-year period were followed
      until they either received a kidney transplant or died. In our hospital, as a
      policy, patients are offered hemodialysis as a bridge therapy to a kidney
      transplant. The mean duration of follow up was 3 months (range 1-11.8 months).
      The factors associated with at least one episode of infection were evaluated.
      Statistical analysis was done by multivariate stepwise logistic regression
      method. Fifty-one patients had a total of 57 episodes (67.8%) of infection. Of
      the 44 episodes of acute bacterial infections, vascular access exit site
      infection was the commonest followed by septicemia (13 patients, 29.5%).
      Staphylococcus aureus was the commonest bacterial isolate observed in 14
      patients. On multivariate analysis, three risk factors for infection were
      identified: (1) nonarteriovenous fistula (AVF) vascular access for hemodialysis
      (p = 0.02), (2) increased number of hemodialysis sessions (p = 0.03), and (3)
      lower serum calcium level (p = 0.02). NonAVF vascular access was found to be the
      most important risk factor for infection in hemodialysis patients. Creation of an
      AV fistula, preferably at an early stage, appears beneficial for minimizing the
      risk of infection even in patients who are on short-term hemodialysis as a bridge
      therapy towards a kidney transplant.

PMID- 14669856
TI  - Peritoneal infection in acute intermittent peritoneal dialysis.
AB  - A prospective study was done to evaluate the incidence and microbiological trend
      of peritoneal infection in patients undergoing acute intermittent peritoneal
      dialysis (PD). Complete sterile procedure was ensured and at the completion of
      the procedure PD fluid was sent for bacteriological culture, sensitivity, and
      total and differential cell count. During the period September 2000 to February
      2001 a total of 100 patients were evaluated. Male female ratio was 72:28. Mean
      age was 43.17 +/- 17.2 years. In 26 patients cyclers were used. Bacterial culture
      was positive in total of 30 cases (30%). Gram positive, Gram negative and mixed
      infection was found in 10%, 15%, and 5% respectively. Number of exchanges (31.61
      +/- 7.7 vs. 31.3 +/- 6, p = 0.8) were similar and number of repositioning was
      significantly more in the infected group (23.3% vs. 11.4%, p < 0.01). Total cell
      count was significantly higher in infected group (274.3 +/- 502 vs. 31.25 +/-
      79.34, p < 0.01). Among Gram +ve organisms Staphylococcus was found in 7,
      Enterococcus faecalis in 4 and Coryne bacterium sps. in 2 cases. Among Gram -ve
      organisms, E. coli was found in 4, Enterobacter in 3, Klebsiella 1, Pseudomonas
      1, Acinetobacter arinatus 5, Acinetobacter baumani 3, and Citrobacter freundii 3.
      Mixed flora comprised of Enterococcus faecalis 3, Enterobacter 1, Staphlococcus
      1, E. coli 3, Citrobacter 1, Acinobacter baumani 1. Although with the cyclers
      using collapsible bags, staphylococcus was not isolated, the total incidence of
      infection (11/26 cases) was not decreased with the use of cyclers. We conclude
      that in acute intermittent peritoneal dialysis the incidence of bacterial
      infection is 30% with preponderance of Gram -ve over Gram +ve organisms and
      organism of fecal origin being commoner than those of skin origin. Use of cycler
      assisted over manual PD do not improve the incidence of infection. Repositioning
      of the stiff catheter significantly increases the incidence of infection.

PMID- 14669857
TI  - The use of ultrasonography in evaluating adults with febrile urinary tract
      infection.
AB  - BACKGROUND: Urinary tract infection (UTI) is a common disease. Controversy exists
      about the role of radiological evaluation in the patient with urinary tract
      infection. MATERIALS AND METHODS: From April 2001 to December 2001, patients with
      febrile UTI admitted to Chang Gung Memorial Hospital, Chiayi were prospectively
      evaluated by ultrasonography. The inclusion criteria of febrile UTI was a body
      temperature of more than 38 degrees C with a bacterial count of 10(3) or more per
      mL in a freshly voided midstream or catheterized urine. RESULTS: A total of 94
      patients were evaluated and all patients recovered. Major abnormal sonograms were
      present in 17 (18%) of the patients. A history of urolithiasis and a duration of
      fever > or = 3 days after admission were statistically significant clinical
      parameters in predicting major abnormal sonogram. Although diabetes mellitus was
      not statistically significant in predicting major abnormal sonogram, diabetic
      patients had 2.5 times the likelihood of major structural abnormalities than
      nondiabetic patients. CONCLUSION: Ultrasonographic study of patients with febrile
      UTI should be limited only to those with a duration of fever > or = 3 days and a
      history of urolithiasis. Ultrasonographic study should also be considered in
      febrile UTI patients with diabetes mellitus.

PMID- 14669858
TI  - Clinical and pathological characterization of patients with microscopic
      polyangiitis with medium artery involvement.
AB  - OBJECTIVE: To study the clinical and pathological characteristics of patients
      with microscopic polyangiitis (MPA) with medium artery involvement. METHODS:
      Hospitalized patients with MPA in recent two years were retrospectively studied.
      Their clinical and pathological features were compared between patients with and
      without renal medium artery involvement. RESULTS: Thirty-nine patients had renal
      pathology confirmed MPA. Nine cases were with medium artery involvement. For the
      30 patients without medium artery involvement, 24/30 had crescentic
      glomerulonephritis and 11/30 also had focal segmental glomerular fibrinoid
      necrosis; clinically, 21/30 patients were pANCA/MPO-ANCA positive, 26/30 had
      acute renal failure with an average duration of 14 weeks before MPA was
      diagnosed, eight cases achieved complete remission after intensive
      immunosuppressive therapy. Nine MPA patients had medium artery involvement,
      manifested as segmental fibrinoid necrosis of major branch of arcuate artery,
      glomerulus ischemia was predominant, but crescentic lesions were mild, none of
      them reached crescentic glomerulonephritis. Five of the nine were pANCA/MPO-ANCA
      positive, eight out of the nine patients had acute renal failure with an average
      duration of eight weeks before diagnosed, seven of the nine achieved complete
      remission after intensive immunosuppressive therapy. In comparison, MPA with
      medium artery involvement had a shorter duration (p < 0.05), less crescentic
      glomerulonephritis in patients with acute renal failure (p < 0.01) and more
      patients achieved complete remission after treatment (p < 0.05). CONCLUSION: In
      present study, about 23% MPA patients had medium artery involvement and their
      impaired renal function is mainly due to extensive glomerular ischemia. These
      patients progressed to acute renal failure quicker and responded to therapy
      better.

PMID- 14669859
TI  - Serum protein-bound 3,4-dihydroxyphenylalanine and related products of protein
      oxidation and chronic hemodialysis.
AB  - INTRODUCTION: Protein-bound dihydroxyphenylalanine (PB-DOPA) and its oxidation
      products are formed by free radical and oxidative attack on proteins.
      Hemodialysis and uremic toxins can activate leukocytes leading to overproduction
      of reactive oxygen species such as hydrogen peroxide and hypochlorous acid (HOCl)
      that increases protein oxidation. METHODS: We have used a sensitive fluorometric
      method to measure PB-DOPA and its oxidation products in proteins after gamma
      irradiation and incubation with HOCl and in serum from hemodialysis patients and
      healthy controls. These PB-DOPA concentrations were compared with those measured
      by HPLC (PB-DOPAHPLC). RESULTS: Fluorescent PB-DOPA increased linearly with
      increasing amounts of human serum and with increasing amounts of gamma-irradiated
      bovine serum albumin. Concentrations of fluorescent PB-DOPA paralleled PB
      DOPAHPLC levels but were approximately 60-70 times higher. Incubation of BSA and
      human serum albumin (HSA) with HOCl (39.4 mM) significantly (P < 0.0001)
      increased fluorescent PB-DOPA by 5 fold and 10 fold respectively and PB-DOPAHPLC
      by 6-fold for both proteins Fluorescent PB-DOPA concentration increased
      significantly (P < 0.0001) by 16-fold in human serum incubated with HOCl (39.4
      mM). Mean serum fluorescent PB-DOPA was significantly (P < 0.0001) higher in 19
      hemodialysis patients (57.7 +/- 16.1 microM) compared with 21 healthy controls
      (33.5 +/- 3.7 microM). Mean PB-DOPAHPLC was 4.45 +/- 1.63 microM in the healthy
      controls and 12 hemodialysis patients had values within the range of values in
      these controls while five patients had values that were outside eight SDs of the
      mean for healthy subjects. Serum fluorescent PB-DOPA was not correlated
      significantly with PB-DOPAHPLC in these subjects. CONCLUSIONS: The results of
      this study suggest that fluorophores of the type, which are derived from DOPA can
      be reproducibly measured in delipidated serum protein and that HOCl can increase
      levels of these fluorophores-generating proteins and may potentially contribute
      to the high levels in serum from hemodialysis patients. This high level of
      fluorescent PB-DOPA compounds is only partially due to authentic PB-DOPA and
      might also be derived from other related protein oxidation products including
      those from DOPA oxidation.

PMID- 14669860
TI  - Which parameter is more influential on the development of arteriosclerosis in
      hemodialysis patients?
AB  - Arteriosclerosis is characterized by stiffening of arteries. The incremental
      elastic modulus (Einc) measurement is a good marker of arterial wall stiffness.
      Metabolic, inflammatory and hemodynamic alterations cause structural changes and
      vascular complications in end stage renal disease. The aim of the present study
      was to evaluate the factors that may affect the development of arteriosclerosis
      by measurement of Einc in hemodialysis (HD) patients. Thirty-two patients (16
      men; 16 female) on chronic HD with a mean age of 42.2 +/- 19.3 (range: 15-80)
      were included in the study. The carotid Einc was measured to determine
      arteriosclerosis by high-resolution echo-tracking system (Acuson Aspen, Acuson
      Corp., Mountain View, California, USA). Einc measurement was calculated from
      transcutaneous measurements of common carotid arterial (CCA) internal diameter
      and wall thickness and carotid pulse pressure. Common carotid compliance and
      distensibility were determined from changes in carotid artery diameter during
      systole and simultaneously measured carotid pulse pressure. Common carotid artery
      stuffiness (Einc) was influenced by age, systolic blood pressure (SBP), pulse
      pressure (PP), calcium (Ca) and alkaline phosphatase (ALP). The distensibility of
      CCA was correlated with age, SBP, diastolic blood pressure (DBP), PP, Ca, ALP,
      and parathormone (PTH). The inflammatory parameter, hs-CRP, was increased with
      Einc. The mean Einc measurement was found significantly increased in patient
      receiving vitamin D. In conclusion, the stiffening of carotid artery in HD
      patients is related not only to hemodynamic changes (increased SBP, PP) but also
      to metabolic (increased Ca) and to inflammation (increased hs-CRP). Carotid Einc
      is accepted independent risk factor for cardiovascular mortality. Because of the
      positive correlation between Einc and serum Ca, vitamin D and Ca containing
      phosphorus (P) binders should be used carefully.

PMID- 14669861
TI  - Association of atherosclerotic coronary artery disease and pulse pressure with
      renal disease progression.
AB  - BACKGROUND: This study was performed to identify the association of
      atherosclerotic coronary artery disease (CAD) and pulse pressure with renal
      disease progression in patients with mild chronic renal disease. METHODS:
      Eligibility criteria for enrollment in this study included age 18 to 70 years,
      mild chronic renal disease (CRD), undergoing thallium SPECT and echocardiography
      and followed longer than three years. Mild CRD was defined as serum creatinine
      level of 1.5 to 3.0 mg/dL in men and 1.4 to 3.0 mg/dL in women. Patients with
      serious illness, history of kidney transplantation, ejection fraction less than
      40% on echocardiography and development of acute renal failure during follow-up
      were excluded. RESULTS: A total of 87 patients were included in this study. The
      underlying renal disease included diabetic nephropathy in 51 patients. Forty-five
      patients showed positive findings on thallium SPECT and they were classified as
      having CAD. Coronary angiography showed significant stenosis in 41 of 42 patients
      studied. Median duration of follow-up was 56 months. During the follow-up period,
      40 patients required chronic dialysis therapy and 16 patients showed a doubling
      of baseline serum creatinine in three years. These 56 patients were classified as
      progressors. Comparison of clinical and laboratory parameters between progressors
      and nonprogressors showed a difference in the presence of diabetic nephropathy,
      mean arterial pressure, 24-h urine protein (p < 0.001), pulse pressure (p <
      0.01), total cholesterol and presence of CAD (p < 0.05). There was no association
      between the progression of CRD and the results of CAD or treatment of CAD.
      Multivariate logistic regression analysis showed that the presence of diabetic
      nephropathy and mean arterial pressure > 100 mm Hg were independent predictors of
      CRD progression. CONCLUSION: Atherosclerotic coronary artery disease and pulse
      pressure were associated with renal disease progression.

PMID- 14669862
TI  - Bilateral renal infarction in chronic myelomonocytic leukemia on blast crisis.
AB  - The major complications of myelodysplastic syndromes are related to cytopenia and
      evolution to acute myeloid leukemia. Bleeding episodes in MDS, although
      relatively uncommon, are often related to thrombocytopenia. Bleeding may be
      exacerbated by platelet dysfunction, which is also found frequently. Furthermore,
      the major hemostatic problem underlying hyperleukocytosis, as evident in patients
      with MDS on blast crisis, appears to be hemorrhage rather than thrombosis. Acute
      thromboembolism, which causes occlusion of blood supply and organ infarction, has
      rarely been observed in patients with MDS. Recently, we encountered an elderly
      female patient, who had chronic myelomonocytic leukemia with marked
      myelodysplasia, terminating in blast crisis and bilateral renal infarction. This
      complication rapidly led to oliguric acute renal failure and mortality.

PMID- 14669863
TI  - A patient with classical polyarteritis nodosa evolving into end stage renal
      failure.
AB  - Classical polyarteritis nodosa (c-PAN) is a form of systemic necrotizing
      vasculitis mainly affecting medium-size arteries, is not associated with renal
      glomerular disease and acute renal failure. Perirenal hematoma can be seen in up
      to fifty percent of c-PAN patients and minority of them develop mild renal
      impairment. Herein, we describe a 34-year-old male with c-PAN who presented with
      rapidly progressive renal failure and evolved into end stage renal disease.

PMID- 14669864
TI  - Is it possible to diagnose primary anti-phospholipid syndrome (PAPS) on the basis
      of renal thrombotic microangiopathy (PAPS nephropathy) in the absence of other
      thrombotic process?
AB  - The kidneys are a major target of PAPS. The histologic lesions of PAPS
      nephropathy are vascular; among them thrombotic microangiopathy (TMA) is the most
      characteristic. It is still not clear in the literature whether the nephropathy
      can be the unique manifestation of PAPS in the absence of other thrombotic
      processes; that is: do the renal microthrombotic lesions allow to make the
      diagnosis of PAPS in presence of anti-phospholipid antibodies (APA)? With this
      purpose we present three clinical cases. The first patient had severe
      hypertension C4 hypocomplementemia, thrombocytopenia, and mitralic valve
      insufficiency. LAC and anti-cardiolipin antibodies at high titre were positive.
      The histologic picture was characterized by basement membrane reduplication and
      arteriolar mucoid degeneration, which are features of early phase of TMA. The
      second patient had severe hypertension. The detection of anti-cardiolipin
      antibodies was performed several times and resulted positive three times, four
      months after the diagnosis as well. The renal histologic features were consistent
      with late lesions of TMA. The third patient had severe hypertension, rapidly
      progressive renal failure, tricuspidal valve insufficiency and two positive anti
      phospholipid antibodies determinations three weeks apart (in two occasions anti
      cardiolipin and in one occasion LAC as well were found). The renal lesions were
      characteristic for TMA. In conclusion we think that patients with TMA and
      antiphospholipid antibodies can be considered affected by PAPS, as the thrombotic
      process is represented by thrombosis in preglomerular arterioles, which leads to
      TMA.

PMID- 14669865
TI  - Focal segmental glomerulosclerosis in a patient with large bilateral asymptomatic
      adrenal myelolipomas.
AB  - Adrenal myelolipomas are rare benign tumors, usually discovered by chance in
      patients with hypertension, obesity or various endocrine disorders. Focal
      segmental glomerulosclerosis (FSGS) can occur as a primary disease or in a
      variety of secondary settings. So far, no association between the two conditions
      has been described. We report a case of a woman admitted for nephrotic syndrome,
      in which a coexistence of FSGS and bilateral large adrenal myelolipomas was
      revealed.

PMID- 14669866
TI  - Vascular endothelial growth factor may provide additional values to C-reactive
      protein and anti-myeloperoxidase titer as a parameter for evaluating disease
      activity in anti-myeloperoxidase associated vasculitis.
AB  - Anti-myeloperoxidase (anti-MPO) associated vasculitis can result in rapid
      clinical deterioration. Immunosuppressive therapy is effective but involving
      considerable toxicity, and disease relapse frequently ensues. Laboratory
      parameters, such as C-reactive protein and anti-MPO titer, have substantial
      values in monitoring disease activity. However, the sensitivity and specificity
      are not satisfactory. This report presents the case of an old man with anti-MPO
      associated vasculitis. A parallel correlation between serum VEGF levels with C
      reactive protein and anti-MPO titer was clearly demonstrated, implying a
      promising role of VEGF on monitoring disease activity in anti-MPO associated
      vasculitis. This is the first description of a correlation between VEGF and anti
      MPO associated vasculitis.

PMID- 14669867
TI  - Degradation of polycyclic aromatic hydrocarbons and long chain alkanes at 60-70
      degrees C by Thermus and Bacillus spp [corrected].
AB  - Although polycyclic aromatic hydrocarbons (PAH) and alkanes are biodegradable at
      ambient temperature, in some cases low bioavailabilities are the reason for slow
      biodegradation. Considerably higher mass transfer rates and PAH solubilities and
      hence bioavailabilities can be obtained at higher temperatures. Mixed and pure
      cultures of aerobic, extreme thermophilic microorganisms (Bacillus spp., Thermus
      sp.) were used to degrade PAH compounds and PAH/alkane mixtures at 65 degrees C.
      The microorganisms used grew on hydrocarbons as sole carbon and energy source.
      Optimal growth temperatures were in the range of 60-70 degrees C at pH values of
      6-7. The conversion of PAH with 3-5 rings (acenaphthene, fluoranthene, pyrene,
      benzo[e]pyrene) was demonstrated. Efficient PAH biodegradation required a second,
      degradable liquid phase. Thermus brockii Hamburg metabolized up to 40 mg (1 h)(
      1) pyrene and 1000 mg (1 h)(-1) hexadecane at 70 degrees C. Specific growth rates
      of 0.43 h(-1) were measured for this strain with hexadecane/pyrene mixtures as
      the sole carbon and energy source in a 2-liter stirred bioreactor. About 0.7 g
      cell dry weight were formed from 1 g hydrocarbon. The experiments demonstrate the
      feasibility and efficiency of extreme thermophilic PAH and alkane biodegradation.

PMID- 14669868
TI  - Effects of heterogeneity and experimental scale on the biodegradation of diesel.
AB  - Biodegradation of petroleum hydrocarbon contamination is a common method for
      remediating soils and groundwater. Due to complexities with field-scale studies,
      biodegradation rates are typically evaluated at the bench-scale in laboratory
      studies. However, important field conditions can be difficult to mimic in the
      laboratory. This study investigates three scaling factors that can impact
      laboratory biodegradation rates and that are frequently unaccounted for in
      typical laboratory experimental procedures. These factors are soil heterogeneity,
      morphology of petroleum hydrocarbon non-aqueous phase liquids (NAPLs) and soil
      moisture distribution. The effects of these factors on the biodegradation rate of
      diesel NAPL is tested under a variety of experimental procedures from well-mixed
      batch studies to four-foot static soil columns. The results indicate that a high
      degree of variability results from even small-scale heterogeneities. In addition,
      it appears that as the experimental scale increases, the measured biodegradation
      rates slow. The results indicate that diesel biodegradation rates derived from
      small-scale experiments are not necessarily representative of field-scale
      biodegradation rates.

PMID- 14669869
TI  - Enrichment of a microbial culture capable of reductive debromination of the flame
      retardant tetrabromobisphenol-A, and identification of the intermediate
      metabolites produced in the process.
AB  - Tetrabromobisphenol-A is a reactive flame retardant used in the production of
      many plastic polymers. In previous research, it was demonstrated that anaerobic
      microorganisms from contaminated sediment debrominate tetrabromobisphenol-A to
      bisphenol-A, but an enrichment culture was not established. The current study was
      carried out to identify the intermediate metabolites in this process and to
      determine the factors facilitating enrichment of debrominating microorganisms.
      During the enrichment process in an anaerobic semi-continuous batch reactor,
      tetrabromobisphenol-A debromination gradually slowed down with concurrent
      accumulation of three intermediate products. These compounds were tentatively
      identified using GC-MS as tri-, di-, and mono-brominated bisphenol-A. GC-MS and
      HPLC analyses showed one dominant metabolite of dibromobisphenol-A, and NMR
      analysis identified it as 2,2'-dibromobisphenol-A. Addition of sterile sediment
      (15% wt/wt) to the reactor stimulated debromination of tetrabromobisphenol-A.
      Furthermore, different solid amendments such as surface soil and pulverized gray
      chalk from the site subsurface (100 m below ground) were also stimulating agents.
      We conclude that organic matter is involved in stimulation since the stimulation
      effect of the sediment, soil and gray chalk was abolished after it was heat
      treated to 550 degrees C. Our study suggests that the debrominating culture
      requires some organic components found in the sediment, soil, and chalk in order
      to sustain activity and perhaps to survive. The possible mechanisms of
      stimulation by these solids are discussed.

PMID- 14669870
TI  - Microsomal transformation of organophosphorus pesticides by white rot fungi.
AB  - The enzymatic mechanism for the transformation of organophosphorus pesticides
      (OPPs) by different white-rot fungi strains was studied. With the exception of
      Ganoderma applanatum 8168, all strains from a collection of 17 different fungi
      cultures were able to deplete parathion. Three strains showing the highest
      activities were selected for further studies: Bjerkandera adusta 8258, Pleurotus
      ostreatus 7989 and Phanerochaete chrysosporium 3641. These strains depleted 50 to
      96% of terbufos, azinphos-methyl, phosmet and tribufos after four-days exposure
      to the pesticides. In order to identify the cellular localization of the
      transformation activity, the extracellular and microsomal fractions of Pleuronts
      ostreatus 7989 were evaluated in vitro. While the activities of ligninolytic
      enzymes (lignin peroxidase, manganese peroxidase and laccase) were detected in
      the extracellular fraction, no enzymatic modification of any of the five
      pesticides tested could be found, suggesting the intracellular origin of the
      transformation activity. In accordance with this observation the microsomal
      fraction was found able to transform three OPPs with the following rates: 10
      micromol mg prot(-1) h(-1) for phosmet, 5.7 micromol mg prot(-1) h(-1) for
      terbufos, and 2.2 micromol mg prot(-1) h(-1) for azinphos-methyl. The products
      from these reactions and from the transformation of trichlorfon and malathion,
      were identified by mass-spectrometry. These results, supported by specific
      inhibition experiments and the stringent requirement for NADPH during the in
      vitro assays suggest the involvement of a cytochrome P450.

PMID- 14669871
TI  - Effects of oxygen and nitrogen conditions on the transformation kinetics of 1,2
      dichloroethenes by Methylosinus trichosporium OB3b and its sMMOC mutant.
AB  - Transformation kinetics of trans- and cis-dichloroethylenes (DCE) by Methylosinus
      trichosporium OB3b wild type (WT) and PP319, a mutant that expresses soluble
      methane monooxygenase at copper levels up to micro 12 microM Cu (sMMOC), were
      determined to assess the effects of O2 level and N2-fixation on degradation
      capabilities. Two issues were examined: (1) the influence of O2 level and
      nitrogen-limitation on DCE degradation kinetics and toxicity in both organisms,
      and (2) the relative utility of PP319 for contaminant degradation in bioreactors.
      When both organisms were grown under high O2 conditions (80% saturation in air),
      maximum transformation rates (Vmax) and apparent first-order rate constants
      (Vmax/KM) were lower compared with organisms grown under low O2 conditions (10%
      saturation in air) regardless of nitrogen level. Further, Vmax values were near
      zero in nitrogen-limited WT cultures when O2 was high (as expected), whereas
      PP319 retained moderate Vmax levels even at high O2 levels. In general, elevated
      O2 conditions reduced DCE degradation rates in OB3b, although the negative
      effects of O2 were less in PP319 than in the WT. Given that PP319 retained
      moderate DCE degradation rates under most O2 and copper conditions, the mutant
      appears to have some utility for biodegradation applications.

PMID- 14669872
TI  - Addressing biofilter limitations: a two-phase partitioning bioreactor process for
      the treatment of benzene and toluene contaminated gas streams.
AB  - A two-phase partitioning bioreactor (TPPB) achieved simultaneous and continuous
      removal and degradation of benzene and toluene from an air stream. The aqueous-
      organic system utilized n-hexadecane as the organic phase, and the organism
      Alcaligenes xylosoxidans Y234 in the aqueous phase to achieve the degradation of
      benzene and toluene. The system, which operates as a well-mixed dispersion and is
      therefore resistant to substrate surges, was first shown to be capable of
      utilizing toluene while operating at a loading capacity of 235 g m(-3) h(-1) with
      an elimination capacity of 233 g m(-3) h(-1). It was also determined that to
      characterize TPPB performance in terms of elimination capacity the definition of
      elimination capacity must be extended to include the cell mass present, a readily
      controllable variable given the nature of the system. Based on this criterion, it
      was estimated that for a cell concentration of 1 g l(-1) present in the TPPB, the
      potential maximum toluene elimination capacity is 1290 g m(-3) h(-1) which is
      substantially higher than any toluene elimination capacity achieved by biofilters
      at a high removal efficiency. If no other factor were to limit the system,
      elimination capacities could be many times higher still, and are dependent on
      maintaining desired cell concentrations above 1 g l(-1). The TPPB was then
      operated at nominal loading capacities of 63 g m(-3) h(-1) (benzene) and 51 g m(
      3) h(-1) (toluene) at a removal efficiency greater than 99% to demonstrated the
      applicability of this system in dealing with two chemical species simultaneously.
      TPPB systems therefore have been shown to be effective at removing gaseous
      organic contaminants at high removal efficiencies while also possessing desirable
      operating features, such as providing and maintaining high cell concentrations
      throughout the reactor, and a capacity to effectively deal with high contaminant
      loadings.

PMID- 14669873
TI  - Advances in biotreatment of acid mine drainage and biorecovery of metals: 1.
      Metal precipitation for recovery and recycle.
AB  - Acid mine drainage (AMD), an acidic metal-bearing wastewater, poses a severe
      pollution problem attributed to post mining activities. The metals usually
      encountered in AMD and considered of concern for risk assessment are arsenic,
      cadmium, iron, lead, manganese, zinc, copper and sulfate. The pollution generated
      by abandoned mining activities in the area of Butte, Montana has resulted in the
      designation of the Silver Bow Creek-Butte Area as the largest Superfund (National
      Priorities List) site in the U.S. This paper reports the results of bench-scale
      studies conducted to develop a resource recovery based remediation process for
      the clean up of the Berkeley Pit. The process utilizes selective, sequential
      precipitation (SSP) of metals as hydroxides and sulfides, such as copper, zinc,
      aluminum, iron and manganese, from the Berkeley Pit AMD for their removal from
      the water in a form suitable for additional processing into marketable
      precipitates and pigments. The metal biorecovery and recycle process is based on
      complete separation of the biological sulfate reduction step and the metal
      precipitation step. Hydrogen sulfide produced in the SRB bioreactor systems is
      used in the precipitation step to form insoluble metal sulfides. The average
      metal recoveries using the SSP process were as follows: aluminum (as hydroxide)
      99.8%, cadmium (as sulfide) 99.7%, cobalt (as sulfide) 99.1% copper (as sulfide)
      99.8%, ferrous iron (sulfide) 97.1%, manganese (as sulfide) 87.4%, nickel (as
      sulfide) 47.8%, and zinc (as sulfide) 100%. The average precipitate purity for
      metals, copper sulfide, ferric hydroxide, zinc sulfide, aluminum hydroxide and
      manganese sulfide were: 92.4, 81.5, 97.8, 95.6, 92.1 and 75.0%, respectively. The
      final produced water contained only calcium and magnesium and both sulfate and
      sulfide concentrations were below usable water limits. Water quality of this
      agriculturally usable water met the EPA's gold standard criterion.

PMID- 14669874
TI  - Advances in biotreatment of acid mine drainage and biorecovery of metals: 2.
      Membrane bioreactor system for sulfate reduction.
AB  - Several biotreatmemt techniques for sulfate conversion by the sulfate reducing
      bacteria (SRB) have been proposed in the past, however few of them have been
      practically applied to treat sulfate containing acid mine drainage (AMD). This
      research deals with development of an innovative polypropylene hollow fiber
      membrane bioreactor system for the treatment of acid mine water from the Berkeley
      Pit, Butte, MT, using hydrogen consuming SRB biofilms. The advantages of using
      the membrane bioreactor over the conventional tall liquid phase sparged gas
      bioreactor systems are: large microporous membrane surface to the liquid phase;
      formation of hydrogen sulfide outside the membrane, preventing the mixing with
      the pressurized hydrogen gas inside the membrane; no requirement of gas recycle
      compressor; membrane surface is suitable for immobilization of active SRB,
      resulting in the formation of biofilms, thus preventing washout problems
      associated with suspended culture reactors; and lower operating costs in membrane
      bioreactors, eliminating gas recompression and gas recycle costs. Information is
      provided on sulfate reduction rate studies and on biokinetic tests with suspended
      SRB in anaerobic digester sludge and sediment master culture reactors and with
      SRB biofilms in bench-scale SRB membrane bioreactors. Biokinetic parameters have
      been determined using biokinetic models for the master culture and membrane
      bioreactor systems. Data are presented on the effect of acid mine water sulfate
      loading at 25, 50, 75 and 100 ml/min in scale-up SRB membrane units, under varied
      temperatures (25, 35 and 40 degrees C) to determine and optimize sulfate
      conversions for an effective AMD biotreatment. Pilot-scale studies have generated
      data on the effect of flow rates of acid mine water (MGD) and varied inlet
      sulfate concentrations in the influents on the resultant outlet sulfate
      concentration in the effluents and on the number of SRB membrane modules needed
      for the desired sulfate conversion in those systems. The pilot-scale data
      indicate that the SRB membrane bioreactors systems can be applied toward field
      scale biotreatment of AMD and for recovery of high purity metals and an
      agriculturally usable water.

PMID- 14669875
TI  - Feedback circuits in hepatitis B virus infection.
AB  - A simplified model using kinetic logic is proposed to approach the problem after
      Hepatitis B viral (HBV) infection. It accounts for several stable regimes or
      attractors corresponding to the essential dynamic behaviour of the replication of
      the Hepatitis B virus. Infection with the virus can result in viral clearance,
      fulminant hepatic failure and death, or chronic transmissible infection, that is
      multistationarity corresponding to the existence of the positive feedback circuit
      in our modelling. Another implication of this model is the existence of
      oscillations or homeostatic mechanisms, sometimes observed in the viral cycle,
      consistent with the existence of the negative feedback circuit. Thus, this report
      shows how a simple model of kinetic logic may be used to account for the variety
      of manifestations of HBV infection. This model implies the presence of the
      Hepatitis B e antigen, whose conservation suggests that it plays an important
      role in the life cycle of hepadnaviruses. Its function in the viral cycle is
      still unknown, but our model suggests that this antigen could explain the passage
      from one state of the viral infection (acute or latent) to another, as well as
      the oscillatory behavior which may account for the intermittent symptoms of
      hepatitis observed in some patients. Furthermore, this model shows a virgin
      state. This state is also reached after recovery. The model proposed demonstrates
      that starting from a viral acute infection, the host's immune response, depending
      on the immunological status of the patient, can lead to viral clearance, or to
      periodic spontaneous reactivation.

PMID- 14669876
TI  - Self-programming machines (II): Network of self-programming machines driving an
      Ashby homeostat.
AB  - The progress in artificial intelligence enables us to conceive adaptive systems
      whose characteristics are nearer and nearer to those of living beings. These
      characteristics though depend on ingenious choices by the designer of these
      systems: Initial conditions, parameters, optimisation functions, gradient and
      measure of fitness within the environment. Nevertheless, in living systems which
      are non-finalist, there are no programmers or designers to conceive of such
      ingenious choices. Our paper "Self-Programming Machines (I)" presents a non
      finalist model since initial states and functions are randomly chosen at the
      beginning and once and for all. In spite of the fact that they are non-finalist,
      these machines always stabilise at fixed points when they are connected to an
      external process. This paper studies the dynamics of a mono-layered network of
      self-programming machines driving a real device. "the Ashby homeostat", and shows
      the striking properties of such networks. This system stabilises only at fixed
      points even if it is subjected to small perturbations or intentional breakdowns
      such as a reversal of power supply or disconnection of one or several motors.
      Real and simulated experiences are compared and theoretical results are
      demonstrated.

PMID- 14669877
TI  - Fairly processing rare and common species in multivariate analysis of ecological
      series. Application to macrobenthic communities from Algiers harbour.
AB  - Systematic sampling of communities gives rise to large contingency tables summing
      up possible changes in the assemblages' structure. Such tables are generally
      analysed by multivariate statistical methods, which are ill-suited for
      simultaneously analysing rare and common species (Field et al., 1982). In order
      to separately process species belonging to either of these categories, we propose
      a statistical method to select common species in a sequence of ecological
      surveys. It is based on a precise definition of rarity, and depends on a rarity
      parameter. In this work, this parameter will be optimised so that the sub-table
      of common species captures the essential features of the complete table as well
      as possible. In this way we analysed the spatio-temporal evolution of
      macrobenthic communities from the Algiers harbour to study the pollution
      influence during a year. The examination of the communities' structuring was done
      through Principal Components Analysis (PCA) of the species proportions table.
      Environmental variables were simultaneously sampled. We show that the data
      structure can be explained by about 25% of the total number of present species.
      Two environmental gradients were brought to the fore inside the harbour, the
      first one representing pollution, and the second one representing hydrological
      instabilities. Since rare species can also convey information, the complete table
      was also coded according to a generalised presence/absence index and submitted to
      Correspondence Analysis. The results were consistent with those of PCA, but they
      depended on more species, and highlighted the influence of sedimentology on the
      assemblages composition.

PMID- 14669878
TI  - Relations between bacterial biomass and carbon cycle in marine sediments: an
      early diagenetic model.
AB  - A new model for early diagenetic processes has been developed through a new
      formula explicitly accounting for microbial population dynamics. Following a
      mechanistic approach based on enzymatic reactions, a new model has been proposed
      for oxic mineralisation and denitrification. It incorporates the dynamics of
      bacterial metabolism. We find a general formula for inhibition processes of which
      some other mathematical expressions are particular cases. Moreover a fast
      numerical algorithm has been developed. It allows us to perform simulations of
      different diagenetic models in non-steady states. We use this algorithm to
      compare our model to a classical one (Soetaert et al., 1996). Dynamical
      evolutions of a perturbation of particulate organic carbon (POC) input are
      studied for both models. The results are very similar for stationary cases. But
      with variable inputs, the bacterial biomass dynamics brings about noticeable
      differences, and these are discussed.

PMID- 14669879
TI  - Radio frequency heating of foods: principles, applications and related properties
      -a review.
AB  - Radio frequency (RF) heating is a promising technology for food applications
      because of the associated rapid and uniform heat distribution, large penetration
      depth and lower energy consumption. Radio frequency heating has been successfully
      applied for drying, baking and thawing of frozen meat and in meat processing.
      However, its use in continuous pasteurization and sterilization of foods is
      rather limited. During RF heating, heat is generated within the product due to
      molecular friction resulting from oscillating molecules and ions caused by the
      applied alternating electric field. RF heating is influenced principally by the
      dielectric properties of the product when other conditions are kept constant.
      This review deals with the current status of RF heating applications in food
      processing, as well as product and system specific factors that influence the RF
      heating. It is evident that frequency level, temperature and properties of food,
      such as viscosity, water content and chemical composition affect the dielectric
      properties and thus the RF heating of foods. Therefore, these parameters should
      be taken into account when designing a radio frequency heating system for foods.

PMID- 14669880
TI  - Peptides from milk proteins and their properties.
AB  - This review has attempted to study the literature pertaining to peptides derived
      from milk proteins. Hydrolysis of milk proteins to generate peptides has been
      practiced for a long time and it was recognized early on in this process that the
      taste of hydrolyzates might hinder use of these products in food formulations.
      Modification of protein is necessary to form a more acceptable or utilizable
      product, to form a product that is less susceptible to deteriorative reactions
      and to form a product that is of higher nutritionall quality. Modifications may
      be achieved by a number of chemical and enzymatic means. This review has
      considered only enzymatic modification of dairy proteins. Modified proteins
      contain peptides and some of these peptides have been purified and their
      functionalities have been compared with unmodified proteins. This paper has
      examined the literature pertaining to improvement in functionality of enzyme
      modified proteins. Improvements in solubility, emulsification, foaming and
      gelation were examined. There is limited information available on the sequence of
      the peptides necessary to improve the functional characteristics of proteins.
      Knowing the sequences of desirable functional peptides can lead to genetic
      alteration of proteins to improve functionality. Addition of synthetic peptides
      to intact proteins may be another way in which the functionality of proteins can
      be augmented. Some of the peptides in milk proteins are capable of affecting
      biological functions of an organism. These effects can be antimicrobial and
      probiotic, i.e., prevent the growth and proliferation of undesirable and
      pathogenic organisms, or they may promote the growth of desirable bacteria in the
      digestive tract of humans and animals. Peptides derived from milk protein have
      been shown to exert digestive and metabolic effects as well. They may also
      influence the immune system. These biological effects may play an important role
      in the development of medical foods that treat or mitigate the effects of
      diseases. Proteins are allergens and therefore it is possible that products
      derived from modification of proteins may also be allergens. The known literature
      about the allergenicity of peptides derived from milk proteins has been examined
      in this article. Last, but not the least, the taste attributes of peptides is
      also considered. Bitterness of hydrolyzates is a common occurrence and the
      origins of these bitter peptides and possible ways of mitigating this sensory
      defect has been discussed. Many of the peptides that enhance functionality and
      exert biological activity are likely to be bitter. Therefore, the bitter taste of
      hydrolysis products has to be dealt with in boosting the functional or
      nutraceutical aspects of foods containing these peptides. Analytical techniques
      for sequencing peptides have become more accessible and purification of peptides
      is commercially feasible. Computer based modeling techniques have aided the
      prediction of structures in these peptides. These advances, coupled with the
      advances in biotechnology, promise to revolutionize the future of nutraceutical
      and functional foods.

PMID- 14669881
TI  - Lipase mediated upgradation of dietary fats and oils.
AB  - In the present scenario, fats and oil modification is one of the prime areas in
      food processing industry that demands novel economic and green technologies. In
      this respect, tailored vegetable oils with nutritionally important structured
      triacylglycerols and altered physicochemical properties have a big potential in
      the future market. In this context, it is well established that lipases
      especially microbial lipases, which are regiospecific and fatty acid specific,
      are of immense importance and hence could be exploited for retailoring of
      vegetable oils. Further, of the bulk available, cheap oils could also be upgraded
      to synthesize nutritionally important structured triacylglycerols like cocoa
      butter substitutes, low calorie triacylglycerols, PUFA-enriched and oleic acid
      enriched oils. It is also possible to change the physical properties of natural
      oils to convert them into margarines and hard butter with higher melting points
      or into special low calorie spreads with short or medium chain fatty acids.
      Today, by and large, fat and oil modifications are carried out chemically
      following the method of directed inter-esterification. The process is energy
      intensive and non-specific. Lipase mediated modifications are likely to occupy a
      prominent place in oil industry for tailoring structured lipids since enzymatic
      modifications are specific and can be carried out at moderate reaction
      conditions. However, as a commercial venture, lipases are yet to be fully
      exploited. Once the technologies are established, the demand of lipases in oil
      industry is expected to increase tremendously in the near future for specific
      modifications of fats and oils to meet the changing consumers' dietary
      requirements.

PMID- 14669882
TI  - Calculation of the non-isothermal inactivation patterns of microbes having
      sigmoidal isothermal semi-logarithmic survival curves.
AB  - Sigmoidal isothermal semi-logarithmic survival curves are of two main types;
      starting with a downward and changing to upward concavity and vice versa. Both
      can be described by a variety of mathematical models having 3-4 adjustable
      parameters. The temperature dependence of these models' parameters can be
      described by empirical models, which account for the progressive change in the
      sigmoidal shape, including its disappearance at either high or low temperatures.
      If the temperature history of a heat-treated population of microbial cells or
      spores ('temperature profile') can be described algebraically, then there is a
      way to estimate the survival pattern under these non-isothermal conditions
      without invoking the traditional D and z values, which require forcing straight
      lines through the curved experimental data. The described method is based on the
      assumption that the local slope of the non-isothermal survival curve is that of
      the isothermal curve at the momentary temperature, at a time, which corresponds
      to the momentary survival ratio. It is similar to the method previously proposed
      for microbial populations with a 'power law' type isothermal survival curves,
      except that the time, which corresponds to the momentary survival ratio, is
      calculated either symbolically or numerically as a procedure incorporated in the
      governing differential equation. The method's capabilities are demonstrated with
      simulated survival curves under temperature histories that resemble thermal
      processing of foods. They include heating to different target temperatures and
      starting the cooling at different times.

PMID- 14669883
TI  - The culture of affluence: psychological costs of material wealth.
AB  - Children of affluence are generally presumed to be at low risk. However, recent
      studies have suggested problems in several domains--notably, substance use,
      anxiety, and depression--and 2 sets of potential causes: pressures to achieve and
      isolation from parents. Recognizing the limited awareness of these issues, the
      objectives in this paper are to collate evidence on the nature of problems among
      the wealthy and their likely causes. The first half of the paper is focused on
      disturbances among affluent children and the second half is focused on
      characteristics of their families and neighborhoods. Widespread negative
      sentiments toward the rich are then discussed, and the paper concludes with
      suggestions for future work with families at the upper end of the socioeconomic
      spectrum.

PMID- 14669884
TI  - Development of mental attention in gifted and mainstream children: the role of
      mental capacity, inhibition, and speed of processing.
AB  - The study examined performance of 6- to 11-year-old children, from gifted and
      mainstream academic programs, on measures of mental-attentional capacity,
      cognitive inhibition, and speed of processing. In comparison with mainstream
      peers, gifted children scored higher on measures of mental-attentional capacity,
      responded more quickly on speeded tasks of varying complexity, and were better
      able to resist interference in tasks requiring effortful inhibition. There was no
      group difference on a task requiring automatic inhibition. Comparisons between
      older and younger children yielded similar results. Correlations between
      inhibition tasks suggest that inhibition is multidimensional in nature, and its
      application may be affected by task demands. Measures of efficiency of inhibition
      and speed of processing did not explain age or group differences on a complex
      intellective measure of mental-attentional capacity.

PMID- 14669885
TI  - The effect of prior practice on memory reactivation and generalization.
AB  - Three experiments examined the effect of practice on memory performance by 18
      month-old infants. Infants were tested using an imitation paradigm; an adult
      demonstrated a series of actions with objects and infants were given the
      opportunity to reproduce those actions following a delay. Some infants practiced
      the target actions before the retention interval (practice) and some did not (no
      practice). In Experiment 1, a reminder treatment alleviated forgetting by infants
      who practiced but failed to alleviate forgetting by infants who did not practice.
      In Experiments 2A and 2B, infants who practiced generalized to novel test stimuli
      after a 24-hr delay, whereas infants without practice did not. Results suggest
      practice influences the accessibility and generality of infants' memories.

PMID- 14669886
TI  - A longitudinal confirmatory factor analysis of indirect and physical aggression:
      evidence of two factors over time?
AB  - The purpose of the present study was to examine whether indirect aggression was
      distinct from physical aggression across developmental periods. Participants were
      3,089 Canadian children aged 4 to 7 years (Time 1), 6 to 9 years (Time 2), and 8
      to 11 years (Time 3). Confirmatory factor analysis using an accelerated
      longitudinal design confirmed a 2-factor model that was stable across cohorts,
      time, and sex. The longitudinal predictive links between indirect and physical
      aggression were also examined in a path analysis. Findings did not support the
      notion that maturation is associated with changes in the ways children aggress
      but rather suggest that children are consistent in the type of aggression they
      use over time, whether it be indirect or physical.

PMID- 14669887
TI  - Social functioning in first grade: associations with earlier home and child care
      predictors and with current classroom experiences.
AB  - Family and child care factors from birth to 54 months, achievement and social
      outcomes at entry to school, and qualities of first-grade classrooms were used to
      predict first-grade social functioning for 864 children from the NICHD Study of
      Early Child Care. Child gender, mothers' partner status, maternal education and
      depressive symptoms, sensitivity of mothering, and amount of time spent in
      nonmaternal child care were significant predictors. Home and child care variables
      predicted social functioning through associations with prior social functioning
      rather than directly. More teacher-led structured activities in first-grade
      classrooms predicted mother's reports of more internalizing behavior. Classrooms
      rated as more emotionally supportive predicted lower levels of mother-reported
      internalizing behavior and concurrently observed indicators of competence.

PMID- 14669888
TI  - Parental dysphoria and children's internalizing symptoms: marital conflict styles
      as mediators of risk.
AB  - Parents' marital conflict styles were investigated as mediators in the
      associations between parental dysphoria and children's internalizing symptoms. A
      community sample of 267 children, ages 8 to 16, participated with their parents.
      Behavioral observations were made of parents' interactions during marital
      conflict resolution tasks. Questionnaires assessed parents' dysphoria and
      children's internalizing problems. Structural equation modeling indicated that
      marital discord, in particular, depressive conflict styles, mediated the
      relationship between parental dysphoria and children's internalizing problems.
      Furthermore, whereas for dysphoric mothers, depressive conflict styles partially
      mediated the links with children's internalizing, for fathers, depressive
      conflict styles fully mediated the links. Destructive and constructive marital
      conflict were associated with parental dysphoria (positively and negatively,
      respectively) but did not mediate the relations with children's internalizing.

PMID- 14669889
TI  - The protective effects of religiousness and parent involvement on the development
      of conduct problems among youth exposed to violence.
AB  - This study examined the protective effects of religiousness and parent
      involvement for the development of conduct problems beyond the effects of risk
      factors. Measures of violence exposure, conduct problems, parent involvement, and
      religiousness, from the longitudinal Social and Health Assessment survey, were
      completed by 1,703 high-risk urban adolescents (12.5 +/- 1.7 years; 53% female).
      Witnessing of and victimization by community violence appeared to be significant
      risk factors for an increase in conduct problems over a 1-year period.
      Religiousness and parental involvement were each uniquely associated with a
      decrease in conduct problems. Moreover, several dimensions of religiousness
      moderated the relationship between violence exposure and conduct problems,
      buffering the negative effects of violence exposure. Implications of these
      findings for prevention efforts are discussed.

PMID- 14669890
TI  - Children and adolescents' internal models of food-sharing behavior include
      complex evaluations of contextual factors.
AB  - This study examined internal representations of food sharing in 589 children and
      adolescents (8-19 years of age). Questionnaires, depicting a variety of contexts
      in which one person was asked to share a resource with another, were used to
      examine participants' expectations of food-sharing behavior. Factors that were
      varied included the value of the resource, the relation between the two depicted
      actors, the quality of this relation, and gender. Results indicate that internal
      models of food-sharing behavior showed systematic patterns of variation,
      demonstrating that individuals have complex contextually based internal models at
      all ages, including the youngest. Examination of developmental changes in use of
      individual patterns is consistent with the idea that internal models reflect age
      specific patterns of interactions while undergoing a process of progressive
      consolidation.

PMID- 14669891
TI  - False belief reasoning and the acquisition of relative clause sentences.
AB  - Perner (1991) has claimed that the linguistic structures and reasoning tasks
      mastered by 4-year-olds share a requirement to handle metarepresentation. In
      contrast, de Villiers (2000) has argued that they share a requirement to handle
      misrepresentation. In the current study, a correlation is observed between
      success on false belief tasks and the acquisition of relative clause sentences.
      This correlation is not predicted by de Villiers's account because such sentences
      do not require the handling of misrepresentation, but it is consistent with
      Perner's account because such sentences do require the handling of
      metarepresentation. It is proposed that only an account that integrates the
      accounts of both de Villiers and Perner can explain extant data on language and
      cognition in 4-year-olds.

PMID- 14669892
TI  - Does work pay psychologically as well as economically? The role of employment in
      predicting depressive symptoms and parenting among low-income families.
AB  - This longitudinal study examined quantity and quality of maternal employment as
      predictors of depressive symptoms and parenting style in a sample of 94 low
      income mothers whose 4-year-old children were enrolled in Head Start at baseline.
      Results suggest that answers to the question of whether work "pays" are complex:
      Findings suggest some benefits of greater employment participation while also
      indicating that women holding lower prestige jobs experienced increases in their
      use of negative parenting style, net of baseline demographic and psychological
      characteristics. Sparse evidence for selection processes was found, with
      cohabitation and maternal depressive symptoms modestly predictive of subsequent
      maternal employment. Implications of these findings for welfare reform and
      educationally related policies for low-income families are discussed.

PMID- 14669893
TI  - Acculturation, substance use, and deviant behavior: examining separation and
      family conflict as mediators.
AB  - This longitudinal study examined how separation and family conflict mediated the
      effects of two acculturation variables (English language use and generational
      status) on substance use (alcohol, tobacco, and marijuana use) and deviant
      behavior outcomes in a Mexican American high school age sample. Structural
      equation modeling indicated that separation was a significant mediator of the
      relationship between acculturation and alcohol use, tobacco use, and deviant
      behavior. Family conflict mediated the effects of acculturation on marijuana use
      and deviant behavior. Model comparisons across gender groups suggested that
      generational status was an influential acculturation measure for females but not
      males. Additionally, English language use maintained a direct effect on marijuana
      use among females, whereas this relationship was mediated by separation for
      males.

PMID- 14669894
TI  - Childhood roots of adulthood hostility: family factors as predictors of cognitive
      and affective hostility.
AB  - Childhood predictors of adulthood hostility was examined in a population-based
      sample of 1,004 children and their parents. Parents' Type A behavior, their life
      satisfaction, family's socioeconomic level, and maternal reports of children's
      Type A behavior were obtained for 6-, 9-, and 12-year-old participants. Hostility
      was self-evaluated by these participants 15 years later. Results revealed that
      childhood environment in terms of parental Type A behavior and life
      dissatisfaction as well as children's own Type A behavior predicted their
      adulthood hostility. The findings identified childhood environments that either
      promoted or protected against hostility. Results underline the need to consider
      the conjoint effects of various factors because the same characteristics play
      different roles in different contexts.

PMID- 14669895
TI  - The importance of shared environment in mother-infant attachment security: a
      behavioral genetic study.
AB  - In a sample of 157 monozygotic and dizygotic twins, genetic and environmental
      influences on infant attachment and temperament were quantified. Only unique
      environmental or error components could explain the variance in disorganized
      versus organized attachment as assessed in the Ainsworth Strange Situation
      Procedure. For secure versus nonsecure attachment, 52% of the variance in
      attachment security was explained by shared environment, and 48% of the variance
      was explained by unique environmental factors and measurement error. The role of
      genetic factors in attachment disorganization and attachment security was
      negligible. Genetic factors explained 77% of the variance in temperamental
      reactivity, and unique environmental factors and measurement error explained 23%.
      Differences in temperamental reactivity were not associated with attachment
      concordance.

PMID- 14669896
TI  - An apple is more than just a fruit: cross-classification in children's concepts.
AB  - This research explored children's use of multiple forms of conceptual
      organization. Experiments 1 and 2 examined script (e.g., breakfast foods),
      taxonomic (e.g., fruits), and evaluative (e.g., junk foods) categories. The
      results showed that 4- and 7-year-olds categorized foods into all 3 categories,
      and 3-year-olds used both taxonomic and script categories. Experiment 3 found
      that 4- and 7-year-olds can cross-classify items, that is, classify a single food
      into both taxonomic and script categories. Experiments 4 and 5 showed that 7-year
      olds and to some degree 4-year-olds can selectively use categories to make
      inductive inferences about foods. The results reveal that children do not rely
      solely on one form of categorization but are flexible in the types of categories
      they form and use.

PMID- 14669897
TI  - The development of visual short-term memory capacity in infants.
AB  - Four experiments assessed visual short-term memory capacity in 4- to 13-month-old
      infants by comparing their looking to changing and nonchanging stimulus streams
      presented side by side. In each stream, 1 to 6 colored squares repeatedly
      appeared and disappeared. In changing streams, the color of a different randomly
      chosen square changed each time the display reappeared; the colors remained the
      same in nonchanging streams. Infants should look longer at changing streams, but
      only if they can remember the colors of the squares. The youngest infants
      preferred changing streams only when the displays contained one object, whereas
      older infants preferred changing streams when the displays contained up to 4
      objects. Thus, visual short-term memory capacity increases significantly across
      the first year of life.

PMID- 14669898
TI  - Training transfer between card sorting and false belief understanding: helping
      children apply conflicting descriptions.
AB  - Two studies investigated the parallel developmental progress in theory of mind
      and executive control, as exemplified by correlations between the Dimensional
      Change Card Sorting task (DCCS; Frye, Zelazo, & Palfai, 1995) and the false
      belief task. Experiment 1 with sixty 3-year-old children confirmed earlier
      studies (e.g., Perner & Lang, 2002), suggesting that children's problem with the
      DCCS lies in the redescription of stimulus objects. Experiment 2 with forty-four
      3- to 4-year-olds reinforced the correlational evidence for a developmental link
      by showing transfer of training: False-belief training improved DCCS performance,
      and DCCS training significantly increased children's performance on the false
      belief task. Results are discussed in relation to 5 theories explaining the
      existing correlational evidence.

PMID- 14669899
TI  - The development of subjective group dynamics: children's judgments of normative
      and deviant in-group and out-group individuals.
AB  - A developmental model of subjective group dynamics suggests that social identity
      is sustained first by intergroup biases and later by intragroup biases. In this
      study 476 English children 5 to 11 years old evaluated the English and German
      soccer teams, and judged in-group or out-group members whose attitudes toward the
      teams was normative versus antinormative. Children of all ages expressed
      intergroup bias. Differential evaluation against in-group deviants and in favor
      of out-group deviants strengthened with age. Understanding of targets' relative
      acceptability (differential inclusion) among in-group and out-group members
      mediated the effects of age and intergroup bias on intragroup bias.
      Identification with the in-group moderated the effects only among older children.

PMID- 14669900
TI  - Sources of inflexibility in 6-year-olds' understanding of emotion in speech.
AB  - When utterances contain conflicting emotion cues, 6-year-olds judge emotion from
      content, even when instructed to judge emotion from paralanguage (Morton &
      Trehub, 2001). Two experiments examined the nature of this bias. In Experiment 1,
      priming paralanguage reversed 6-year-olds' normal bias to content. In Experiment
      2, 6-year-olds were instructed to listen to paralanguage under various
      conditions. Children were more likely to follow instructions delivered with
      feedback than instructions delivered alone. Children who described conflicts
      between content and paralanguage were more likely to follow instructions than
      children who did not describe these conflicts. Results suggest that 6-year-olds
      can judge emotion from paralanguage in the presence of competing content but
      often remain focused on content because of the way they represent the
      instructions.

PMID- 14669901
TI  - Adolescents' emotion regulation in daily life: links to depressive symptoms and
      problem behavior.
AB  - This study examined links between emotion regulation and adjustment in a sample
      of 152 adolescents in Grades 7 (M age = 12) and 10 (M age = 15). Emotion
      regulation was assessed using the experience sampling method, in which
      adolescents provided multiple reports about the intensity, lability, and
      strategies used to regulate negative emotions across 1 week. Adolescents also
      completed self-report measures of adjustment. Adolescents who reported more
      intense and labile emotions and less effective regulation of these emotions also
      reported more depressive symptoms and problem behavior. Responding to negative
      emotions with disengagement (e.g., denial) or involuntary engagement (e.g.,
      rumination) was less effective in regulating negative affect, and greater use of
      these strategies was related to higher levels of depressive symptoms and problem
      behavior.

PMID- 14669902
TI  - Observed peer victimization during early elementary school: continuity, growth,
      and relation to risk for child antisocial and depressive behavior.
AB  - The rate at which 266 boys and girls ages 5 to 7 years old were victimized by
      peers was observed on multiple occasions in kindergarten and first grade.
      Individual differences in victimization were observed at kindergarten entry and
      in growth over the subsequent 2 years. Victimization increased for some children
      but decreased for others. Growth in victimization was reciprocally related to
      growth in teacher-reported antisocial and depressive behavior for boys. For
      girls, kindergarten victimization was related to growth in parent-reported
      antisocial behavior, teacher-reported depressive behavior to growth in
      victimization, and growth in victimization to parent-reported depression. At a
      short-term group level, antisocial behavior had a lagged suppressive effect on
      victimization for boys but a facilitating effect for girls.

PMID- 14669903
TI  - Can parents and teachers provide a reliable and valid report of behavioral
      inhibition?
AB  - Reliability and validity of parent and teacher report of behavioral inhibition
      (BI) was examined among children aged 3 to 5 years. Confirmatory factor analysis
      supported 6 correlated factors reflecting specific BI contexts, each loading on a
      single, higher order factor of BI. Internal consistency was acceptable, with
      moderate stability over 1 year and strong correlation with a brief inhibition
      subscale from a temperament questionnaire. Children who were rated by mothers and
      teachers as high BI took longer to initiate contact with a stranger, spoke less
      often and for shorter periods, and required more prompting to elicit speech
      compared with low-BI peers in a simulated stranger interaction task. Father
      report of BI was significantly associated with mean duration of speech and eye
      gaze.

PMID- 14669904
TI  - Children's responses to everyday marital conflict tactics in the home.
AB  - Mothers' and fathers' reports of marital conflicts in the home were obtained (n =
      1,638 and 1,281 conflicts, respectively), including conflicts in front of the
      children (n = 580 and 377, respectively). Participants were 116 families with
      children 8 to 16 years old (M = 10.82 years, SD = 2.17; 58 boys, 58 girls).
      Children's emotional responses indicated distinctions between distressing
      conflict tactics (i.e., threat, personal insult, verbal hostility, defensiveness,
      nonverbal hostility, marital withdrawal, physical distress) and those that
      increased their emotional security (i.e., calm discussion, support, affection).
      Analyses based on cross-reporter informants of parental conflict and child
      responses strengthened confidence in the findings. Conflict tactics were related
      to marital functioning, and children's emotional reactions during marital
      conflicts were associated with their adjustment.

PMID- 14669905
TI  - Examining stress reactivity in neonates: relations between cortisol and behavior.
AB  - The association between cortisol and behavioral reactivity to a medical heel
      stick and a neurobehavioral exam was examined in 100 healthy African American
      neonates, who have been underrepresented in this area of research. Using
      continuous measures, behavioral distress was associated with cortisol reactivity
      to both stressors. High levels of behavioral distress, however, were associated
      with cortisol reactivity only in response to the neurobehavioral exam. In
      contrast, low levels of behavioral distress were associated with cortisol
      reactivity only in response to the heel stick. The results highlight potentially
      important parameters for exploring the relation between biological and behavioral
      reactivity to stress such as the operationalization of behavioral distress and
      the context in which a stress response is elicited.

PMID- 14669907
TI  - Clastogenic effects of streptozotocin on human colon cancer cell lines with gene
      amplification.
AB  - We investigated the clastogenic effects of the methylating agent streptozotocin
      (STZ) on two human colon cancer cell lines. COLO320DM and COLO320HSR are cell
      lines derived from a human neuroendocrine colon carcinoma. STZ produced a dose
      dependent increase in the frequency of chromosomal aberrations in both cell lines
      (p < 0.05) and induced fragmentation and/or pulverization of COLO320DM and
      COLO320HSR chromosomes. This effect was dose and time dependent. Severe
      chromosome damage was also found in cells that had progressed beyond the first
      metaphase, and a higher percentage of metaphases showing pulverized chromosomes
      were found in cells after the second than after the first division. This seems to
      indicate that STZ has a persistent and delayed clastogenic effect on COLO320DM
      and COLO320HSR cells. In addition, STZ produced a marked depression of the
      mitotic index in both cell lines. These results demonstrate that human colon
      cancer cell lines COLO320DM and COLO320HSR are highly sensitive to STZ, and
      suggest that this antibiotic has a good potential as a chemotherapeutic agent for
      colon cancer.

PMID- 14669906
TI  - Human immunodeficiency virus type 1 pharmacogenomics in clinical practice:
      relevance of HIV-1 drug resistance testing (Part 2).
AB  - Throughout most of the past century, physicians could offer patients no
      treatments for infections caused by viruses. The experience with treatment of
      infection by human immunodeficiency virus (HIV) has changed the way healthcare
      workers deal with viral infections and has triggered a growing rate of discovery
      and use of antiviral agents, the first fruits of the expanding genomics
      revolution. HIV treatment also provides an informative paradigm for
      pharmacogenomics because control of infection and its consequences is limited by
      the development of viral drug resistance and by host factors. This report
      summarizes studies published to date on the significance of testing of HIV-1
      resistance to antiretroviral drugs. The only Food and Drug Administration
      approved kit is commercially available through Visible Genetics, Inc., for HIV
      drug resistance testing by genotypic sequencing. Genotyping sequencing alone is
      most likely an adequate test to assist in the therapeutic decision-making process
      in cases of previous regimen failure, treatment-naive patients in areas of high
      prevalence of transmitted resistant virus, and pregnant women. However, in
      exceptional cases of highly complex mutation patterns and extensive cross
      resistance, it may be useful to obtain a phenotype test, because that result may
      more easily identify drugs to which the virus is least resistant. There are no
      published clinical trial results on the usefulness of the so-called virtual
      phenotype over genotypic sequencing alone. The paradigm of viral pharmacogenomics
      in the form of HIV genotypic sequencing has been not only useful to the treatment
      of other viral diseases but also important to the real-life implementation of the
      growing discipline of genomics or molecular medicine. The application of this
      paradigm to the thousands of potential therapeutic targets that have become
      available through the various human genome projects will certainly gradually
      change the landscape of diagnosis and management of many diseases, including
      cancer.

PMID- 14669908
TI  - Histopathological effects of mercury in skin-lightening cream.
AB  - Rose skin-lightening cream with a mercury content of 77,513 +/- 71,063 ppm was
      selected and applied on mice for a period of 1 month at different intervals.
      Mercury levels were measured in a total of 58 liver, kidney, and brain tissue
      samples by atomic absorption spectrophotometer coupled to vapor generator
      accessory. The mean mercury concentration in the tissues of treated mice was
      67,472 +/- 70,181 microg/g in the range of 0.391-288.759 microg/g. Looking at the
      mercury concentration in the tissue samples with respect to the application of
      skin lightening creams at different intervals, the highest mercury concentrations
      were found in the tissues of mice treated 3 times a day (116.806 +/- 83.182
      microg/g, ranges 5.989-288.759 microg/g). On the other hand, the lowest mercury
      concentrations were found in the tissues of mice treated once a week (16.450 +/-
      26.168 microg/g, ranges 0.391-95.642 microg/g). Histopathological changes were
      clearly seen in the brain, kidney, and liver sections of all treated mice. The
      severity of pathological changes observed in tissues increased with increasing
      the number of applications. It is evident that repeated application of Rose skin
      lightening creams could induce permanent damage to the kidneys, brain, and liver.
      This study emphasizes the potential toxicity of mercury skin-lighting creams and
      the importance of discontinuing their manufacture and use.

PMID- 14669910
TI  - Comparison of three methods for epidemiological typing of Campylobacter jejuni
      and C. coli.
AB  - A total of 168 Campylobacter strains (154 C. jejuni and 14 C. coli) isolated from
      human clinical samples and chicken meat were typed using Penner serotyping,
      randomly amplified polymorphic DNA (RAPD), and pulsed-field gel electrophoresis
      (PFGE) with four restriction enzymes (Sac II, Sal I, Sma I, Kpn I). The 168
      strains were found to represent 13 different Penner-types and 72 different RAPD
      types. However, the discriminatory potential of PFGE was dependent on the
      restriction enzymes used. The 168 strains were divided into 74 (Sac II), 73 (Sal
      I), 72 (Sma I) and 69 (Kpn I) types. The DNA of some strains was not digested by
      Sal I, Sma I and Kpn I. Although three RAPD-types were further subdivided by
      PFGE, RAPD showed good discriminatory power and a high level of agreement with
      PFGE patterns in terms of strain differentiation. To compare the similarities of
      PFGE patterns (Sac II) among the strains, a dendrogram was constructed based on
      the unweighted pair group method with averages (UPGMA). In most cases, DNA types
      of C. coli were different from those of C. jejuni. The similarities between human
      and meat isolates were less than 0.42 except for one outbreak in which the
      isolates from both patients and chicken meat showed the same DNA types.

PMID- 14669909
TI  - Expression and characterization of the celcflB gene from Cellulomonas flavigena
      encoding an endo-beta-1,4-glucanase.
AB  - An endoglucanase gene called celcflB was isolated from a genomic library of C.
      flavigena. Its nucleotide sequence showed an ORF of 1725 bp with a GTG start
      codon. A promoter sequence was found inside the adjacent gene upstream from the
      start point of translation of celcflB gene. The gene celcflB was induced by
      sugarcane bagasse and repressed by glucose when C. flavigena was grown on these
      carbon sources, suggesting that celcflB gene is regulated at transcriptional
      level. The predicted amino acid sequence of the CelcflB protein presented a
      catalytic domain with a high homology to family 5 of glycosil hydrolases, and a
      cellulose binding domain identical to cellulose binding domains type II. The
      coding region of the celcflB gene was cloned into the expression vector pQE30 and
      the recombinant protein of 58 kDa presented endoglucanase activity towards
      carboxymethyl cellulose (CMC).

PMID- 14669911
TI  - Expression of binary toxin genes in the mosquito-colonizable bacteria, Bacillus
      cereus, leads to high toxicity against Culex quinquefasciatus larvae.
AB  - Two B. cereus strains, Ae10 and Cx5, isolated from mosquito larval guts, were
      transformed with a recombinant plasmid, pBS373, harboring binary toxin genes from
      Bacillus sphaericus 2297. Immunoblotting analysis clearly revealed the production
      and presence of the 51-kDa toxin protein in both strains. Two recombinant B.
      cereus strains Ae10 and Cx5 showed very high toxicity against C. quinquefasciatus
      larvae. Since both strains have a close relationship with the mosquito larvae in
      the native environment and are capable of recolonizing in the guts of mosquito
      larvae, these strains can be considered promising new hosts for an effective
      delivery of mosquito-larvicidal toxins.

PMID- 14669912
TI  - Biological role of lectins from the nitrogen-fixing Paenibacillus polymyxa strain
      1460 during bacterial-plant-root interactions.
AB  - Enzyme-lectins LI and LII from Paenibacillus polymyxa 1460, when incubated with
      the carbohydrate moiety of the wheat-root exocomponent fraction, showed an
      increase in their proteolytic activity. This increase may be associated with the
      presence of lectin-specific carbohydrates in the root fraction. The lectins of
      the nitrogen-fixing paenibacilli enhance cellulose degradation in the plant cell,
      thus increasing the activity of beta-glucosidase in the wheat-root cell wall.

PMID- 14669913
TI  - Experimental evidence for the physiological role of bacterial luciferase in the
      protection of cells against oxidative stress.
AB  - The origin and function of bioluminescence was considered a problematic question
      of the Charles Darwin theory. Early evolution of bacterial luminescence and its
      current physiological importance seem to be especially mysterious. Recently, it
      was proposed that stimulation of DNA repair may be a physiological role for
      production of light by bacterial cells. On the other hand, it was also proposed
      that primary role of luminescent systems could be detoxification of the
      deleterious oxygen derivatives. Although some previous results might suggest that
      this hypothesis can be correct, until now experimental evidence for such a
      mechanism operating in bacterial cells and having physiological importance was
      generally lacking. Here we demonstrate that in the presence of various oxidants
      (hydrogen peroxide, cumene hydroperoxide, t-butyl hydroperoxide, and ferrous
      ions) at certain concentrations in the culture medium, growth of Vibrio harveyi
      mutants luxA and luxB, but not of the mutant luxD, is severely impaired relative
      to wild-type bacteria. This deleterious effect of oxidants on the mutants luxA
      and luxB could be significantly reduced by addition of the antioxidants A-TEMPO
      or 40H-TEMPO. We conclude that bacterial luciferase may indeed play a
      physiological role in the protection of cells against oxidative stress.

PMID- 14669914
TI  - Efficient expression of the mosquito larvicidal binary toxin gene from Bacillus
      sphaericus in Escherichia coli.
AB  - The binary toxin gene encoding BinA (42 kDa) and BinB (51 kDa) from Bacillus
      sphaericus strain 2297 was cloned and expressed in E. coli. Low expression level
      was found when both proteins were expressed from a single operon. High expression
      was observed when the gene encoding an individual protein was placed downstream
      of the T7 promoter. The expression level of BinB was not different when expressed
      alone (non-fusion) or as a fusion form with T7 peptide (T7-BinB). Both forms of
      BinB were equally stable. Unlike BinB, the non-fusion form of BinA was less
      stable than T7-BinA. The mosquito larvicidal test showed that BinA or BinB alone
      was not toxic to mosquito larvae, but high toxicity was found when both BinA and
      BinB were applied. The results suggest that a short peptide of T7 linked to the N
      terminus of either BinA or BinB does not affect their toxicity, but may make the
      toxin, especially BinA, more stable.

PMID- 14669915
TI  - The 492-bp RM07 DNA fragment from the halophilic Archaea confers promoter
      activity in all three domains of life.
AB  - A 492-bp DNA fragment, designated RM07, was isolated from the chromosomal DNA of
      the halophilic Archaea, Halobacterium halobium, and was shown to confer promoter
      activity in Escherichia coli. Sequence analysis revealed that RM07 contained
      three consensus sequences of the archaeal distal promoter element as well as the
      typical -35 and -10 box sequences of bacterial promoters. Promoter probe analysis
      confirmed that RM07 conferred promoter activity in all three domains of life:
      Archaea (Haloferax volcanii), Eukarya (Saccharomyces cerevisiae) and Bacteria
      (Escherichia coli). Deletion analysis and site-directed mutagenesis further
      identified the functional regions within RM07 required for promoter activity.
      This is the first report of a DNA fragment from Archaea that confers promoter
      activity in all three domains of life, suggesting that the promoter structure and
      activity may be viewed as a bridge narrowing the gaps among the different domains
      of life.

PMID- 14669916
TI  - Sequencing and characterization of plasmid pUIBI-1 from Bacillus thuringiensis
      serovar entomocidus LBIT-113.
AB  - Plasmid pUIBI-1 from Bacillus thuringiensis svr. entomocidus was sequenced and
      its replication mechanism analyzed. Sequence analysis revealed that pUIBI-1
      contains 4671 bp and a 32% GC content. Plasmid pUIBI-1 also includes at least
      seven putative open reading frames (ORFs) encoding for proteins ranging from 5 to
      50 kDa. ORF-1 encodes for a putative 16-kDa Rep protein, which lacks homology
      with proteins of similar function. ORF2 encodes for a protein of 50 kDa and shows
      homology with Mob proteins of plasmids pLUB1000 from Lactobacillus hilgardii
      (32.2%) and pGI2 from B. thuringiensis (33.7%). Detection of single-stranded DNA
      (ssDNA) intermediates indicated that pUIBI-1 replicates by the rolling-circle
      replication mechanism, as demonstrated by S1 treatment and Southern hybridization
      under non-denaturing conditions.

PMID- 14669917
TI  - A simple method for in vivo expression studies of Xanthomonas axonopodis pv.
      citri.
AB  - A major problem in studying bacterial plant pathogens is obtaining the
      microorganism directly from the plant tissue to perform in vivo expression
      (protein or mRNA) analyses. Here we report an easy and fast protocol to isolate
      Xanthomonas axonopodis pv. citri directly from the host plant, in sufficient
      amounts to perform protein fingerprinting by 2-D gel electrophoresis as well as
      RNA expression assays. The protein profile obtained was very similar to that of
      X. axonopodis pv. citri grown in the presence of a leaf extract of Citrus
      sinensis; however, some differential proteins expressed in vivo were observed.
      Total RNA extraction revealed typical 16S and 23S bands in the agarose gel, and
      RT-PCR reactions using primers specific for genes of the bacterium confirmed the
      quality of the RNA preparation. Also, RT-PCR reactions using plant ribosomal
      primers were employed, and no amplification product was obtained, indicating that
      plant RNA is not present in the bacterium RNA sample.

PMID- 14669918
TI  - Hierarchical chromatin structure of Schizosaccharomyces pombe revealed by atomic
      force microscopy.
AB  - Many structural studies on higher eukaryotic chromatin have been carried out, but
      chromatin structure in fungi remains unclear. Schizosaccharomyces pombe has been
      used for investigations of chromosome function; however, the structural details
      of S. pombe chromatin have not been clarified owing to its small nucleus. We used
      atomic force microscopy for nano-scale imaging of chromatin isolated from S.
      pombe. Topographic images indicated that nuclear chromatin contained at least
      three hierarchical structures: large-scale chromatin fibers, spherical domains in
      the fibers, and nodules in the domains. The average diameters of the domain and
      the nodule were 363 +/- 85.2 nm and 46.2 +/- 9.30 nm. Each structure comprising
      the hierarchy was similar to higher eukaryotic chromatin thus far observed,
      despite definite differences in chromatin organization at the nucleosomal level.
      The presence of histone H1 suggested that there might be an alternative to
      compensate for histone H1 lacking in S. pombe.

PMID- 14669919
TI  - Purification and characterization of an extracellular non-aspartyl acid protease
      (pumAe) from Ustilago maydis.
AB  - The proteinase pumAe was purified to homogeneity from haploid U. maydis FB1
      growing on acid mineral medium. The purification procedure consisted of ammonium
      sulfate fractionation and gel filtration chromatography, resulting in a 7.7%
      recovery and a 15.1-fold increase in specific activity. The molecular weight of
      the enzyme was estimated to be 72 kDa and 74 kDa by gel filtration chromatography
      and SDS-PAGE, respectively. Enzymatic activity was optimal at pH 4.0 and at 45
      degrees C toward hemoglobin, and the pI was determined to be 5.5. The effects of
      six protease inhibitors on pumAe were tested, and no inhibitory effect was
      observed. The pure enzyme degraded gelatin and albumin, but casein and collagen
      were not degraded. The Km value was 3.5 microM, and the Vmax value was 11,430
      micromol h(-1) mg(-1) for Suc-R-P-F-H-L-L-V-Y-MCA.

PMID- 14669920
TI  - Microbulbifer arenaceous sp. nov., a new endolithic bacterium isolated from the
      inside of red sandstone.
AB  - An endolithic bacterium, strain RSBr-1, was isolated from the inside of a piece
      of red sandstone from coastal areas of Scotland. RSBr-1 was gram negative,
      oxidase and catalase positive, and cells were non-motile rods. Sodium was
      required for growth. The optimum sodium chloride concentration and pH for growth
      were 4% and pH 8.0, respectively. Eumelanin was produced in marine broth and in
      BY medium. RSBr-1 hydrolyzes chitin, esculin, gelatin, and starch, but not agar.
      Nitrate reduction is positive. Taxonomic characterization of this strain
      indicated that it belongs to the genus Microbulbifer. The difference between the
      aligned 16S rDNA sequences of RSBr-1 and the closest relative, M. elongata, is
      greater than the difference between the 16S rDNA sequences of M. hydrolyticus and
      M. elongata. On the basis of the phenotypic and genotypic comparison of this
      isolate with the other strains, RSBr-1 is proposed as a new species,
      Microbulbifer arenaceous, with type strain RSBr-1.

PMID- 14669921
TI  - Distribution analysis of IS231-like sequences among Bacillus thuringiensis
      serovars inferred from restriction fragment length polymorphisms.
AB  - The distribution of IS231 has been analyzed in Bacillus thuringiensis serovars. A
      723-bp HaeII conserved fragment from IS231M has been used as a probe against
      EcoRI-digested B. thuringiensis total DNA to yield serovar-specific hybridization
      profiles. The approach was useful at revealing the extent of distribution of
      IS231-like sequences between and within strains. Of the 88 B. thuringiensis
      strains tested, 70 showed hybridization banding patterns that comprised between
      one and 20 distinct bands. These 70 B. thuringiensis strains were grouped based
      on banding pattern similarities. Interestingly, intraserovar strains did not
      necessarily cluster together.

PMID- 14669922
TI  - Metabolic changes in Clostridium absonum ATCC 27555 accompanying induction of
      epimerization of a primary bile acid.
AB  - Some parameters of fermentation have been determined for Clostridium absonum in a
      chemostat by using a chemically defined medium with glucose as the sole source of
      carbon and energy. Steady-state continuous cultures were achieved at two dilution
      rates (D). Trends of the carbon flow were determined by comparison of ratios
      between the specific rates of formation of the three products of metabolism
      (lactate, acetate, butyrate). Chenodeoxycholate induced the 7alpha- and 7beta
      hydroxysteroid dehydrogenases of C. absonum. In the presence of this inducer, the
      growth yield and the carbon recovery decreased, the carbon flow distribution was
      altered favoring acetate production, and a deficit in the reoxydation of
      nucleotidic cofactors was observed. In the presence of chenodeoxycholate, C.
      absonum would favor the production of energy at the expense of the reoxidation of
      nucleotidic cofactors so as to ensure its growth, and the epimerization of
      chenodeoxycholate to ursodeoxycholate.

PMID- 14669923
TI  - A motility revertant of the ndvB mutant of Bradyrhizobium japonicum.
AB  - A motility revertant of a Bradyrhizobium japonicum ndvB mutant was isolated and
      characterized. The ndvB mutants of B. japonicum have been reported to be
      osmotically sensitive, as well as defective in motility, periplasmic cyclic beta
      (1-->3), (1-->6)-D-glucan synthesis, and symbiosis with soybean. The motility
      revertant was restored for osmotic tolerance but not for cyclic beta-glucan
      production or effective symbiosis. These results support our hypothesis that
      cyclic beta-glucans have an important role in symbiosis--the suppression of a
      plant defense response--in addition to their role in periplasmic osmoprotection.

PMID- 14669924
TI  - Molecular and structural characterization of the HMP-AB gene encoding a pore
      forming protein from a clinical isolate of Acinetobacter baumannii.
AB  - The major outer membrane protein of Acinetobacter baumannii is the heat
      modifiable protein HMP-AB, a porin with a large pore size allowing the
      penetration of solutes having a molecular weight of up to approximately 800 Da.
      Cross-linking experiments with glutardialdehyde failed to show any cross-linking
      between the monomers, a fact that proves again that this porin protein functions
      as a monomeric porin. The specific activity of this porin was found to be similar
      to that of other monomeric porins. Tryptic digestion of the outer membrane
      yielded a 23-kDa fragment of the HMP-AB protein that was resistant to further
      trypsin treatment. This observation indicates that HMP-AB is assembled in the
      membrane in a manner similar to monomeric porins. Cloning of the HMP-AB gene
      revealed an open reading frame of 1038 bp encoding a protein of 346 amino acids
      and a calculated molecular mass of 35,636 Da. The amino acid sequence and
      composition were typical of gram-negative bacterial porins: a highly negative
      hydropathy index, absence of hydrophobic residue stretches, a slightly negative
      total charge, low instability index, high glycine content, and an absence of
      cysteine residues. Sequence comparison of HMP-AB with other outer membrane
      proteins revealed a clear homology with the monomeric outer membrane proteins,
      outer membrane protein A (OmpA) of Enterobacteria, and outer membrane protein F
      (OprF) of Pseudomonas sp. Secondary structure analysis indicated that HMP-AB has
      a 172-amino acid N-terminal domain that spans the outer membrane by eight
      amphiphilic beta strands and a C-terminal domain that apparently serves as an
      anchoring protein to the peptidoglycan layer. The results also indicate that HMP
      AB belongs to the eight transmembrane beta-strand family of outer membrane
      proteins.

PMID- 14669925
TI  - Nitrogen starvation-induced changes in amino acid and free ammonium pools in
      Schizophyllum commune colonies.
AB  - Wood-decay fungi depend upon recycling of nitrogen-containing molecules to
      maintain growth in nitrogen-deficient environments. One of the pools that can
      support growth in these organisms is the pool of free amino acids. The free amino
      acid (AA) composition of Schizophyllum commune mycelium grown on the surface of
      nitrogen-rich (M = 6.6 mM L-asparagine) and nitrogen-poor medium (M01 = 0.06 mM L
      asparagine) has been examined: When mycelium is grown on M, alanine, glutamate,
      and asparagine account for almost 2/3 of the amino acid pool. The free amino acid
      concentration is reduced by 75% for mycelium grown on the M01 medium, with
      alanine and glutamate predominating. In addition, free NH4+ increases by 60% in
      nitrogen-deprived mycelia. Except for asparagine, which is absorbed by the
      apices, the concentration of all free amino acids is higher in the centers of M
      grown, 4-day-old mycelia than in the apices. Hyphae grown to exponential growth
      on M and transferred to M01 for 12 h show greater free amino acid and NH4+
      concentrations in the apices, most likely indicating increased translocation to
      the apices.

PMID- 14669926
TI  - The effects of deer antler velvet extract or powder supplementation on aerobic
      power, erythropoiesis, and muscular strength and endurance characteristics.
AB  - To determine the effects of deer antler velvet on maximal aerobic performance and
      the trainability of muscular strength and endurance, 38 active males were
      randomly assigned in a double-blind fashion to either deer antler velvet extract
      (n = 12), powder (n = 13), or placebo groups (n = 13). Subjects were tested prior
      to beginning supplementation and a 10-week strength program, and immediately post
      training. All subjects were measured for circulating levels of testosterone,
      insulin-like growth factor, erythropoietin, red cell mass, plasma volume, and
      total blood volume. Additionally, muscular strength, endurance, and VO2max were
      determined. All groups improved 6 RM strength equivalently (41 +/- 26%, p <
      .001), but there was a greater increase in isokinetic knee extensor strength (30
      +/- 21% vs. 13 +/- 15%, p = .04) and endurance (21 +/- 19% vs. 7 +/- 12%, p =
      .02) in the powder compared to placebo group. There were no endocrine, red cell
      mass or VO2max changes in any group. These findings do not support an
      erythropoetic or aerobic ergogenic effect of deer antler velvet. Further, the
      inconsistent findings regarding the effects of deer antler velvet powder
      supplementation on the development of strength suggests that further work is
      required to test the robustness of the observation that this supplement enhances
      the strength training response and to ensure this observation is not a type I
      error.

PMID- 14669927
TI  - Use of dietary supplements by elite figure skaters.
AB  - The present study examined the prevalence of dietary supplement use among elite
      figure skaters, gender differences in supplement use, and differences in nutrient
      intake of supplement users versus non-users. Male (n = 46) and female (n = 59)
      figure skaters completed a supplement survey and 3-day food records. Descriptive
      analysis, chi-square test, and independent t tests were used to analyze the data.
      Sixty-five percent of male (n = 30) and 76% of female (n = 45) figure skaters
      reported use of supplements. Forty-seven percent of males and 55% of females
      reported daily use of supplements. Multivitamin-mineral supplements were the most
      popular dietary supplements consumed by figure skaters. Significant gender
      differences were observed in the use of multivitamin-mineral supplements (61%
      males vs. 83% females, p < .05). Echinacea and ginseng were popular herbal
      supplements used by these skaters. The 3 main reasons given by male figure
      skaters for taking supplements were: to provide more energy (41%), to prevent
      illness or disease (34%), and to enhance performance (21%). Among female figure
      skaters, the 3 main reasons given were: to prevent illness or disease (61%), to
      provide more energy (39%), and to make up for an inadequate diet (28%).
      Significant differences (p < .05) were observed in protein, total fat, saturated
      fat, polyunsaturated fat intakes, and % energy from carbohydrate and total fat of
      male supplement users versus non-users, with supplement users having higher
      intakes except for percent energy from carbohydrate. Sodium was the only nutrient
      significantly different (p < .05) among female supplement users versus non-users,
      with supplement users having lower intakes. Given the popularity of dietary
      supplements, it is important to understand the factors influencing athletes' use
      of supplements, their knowledge and attitudes regarding supplements, dosage of
      supplements used, and the effectiveness of these dietary supplements in meeting
      the goals of the athletes.

PMID- 14669928
TI  - Policies on screening female athletes for iron deficiency in NCAA division I-A
      institutions.
AB  - Iron deficiency is the most prevalent nutritional deficiency in the United
      States. This condition has been reported to affect 60% of female athletes. The
      Centers for Disease Control and Prevention emphasize screening for anemia in
      women of childbearing age. The purpose of this study was to determine the number
      of National Collegiate Athletic Association (NCAA) Division I-A schools that
      implement screening for iron deficiency in female athletes as well as the
      screening policies for those who do. A link to an online survey was sent to 94
      NCAA Division I-A schools to determine current practices concerning screening and
      treating female athletes for iron deficiency. There was a 58% response rate.
      Frequencies for each response were computed. Forty-three percent of responding
      institutions report screening female athletes for iron deficiency. This study
      suggests that screening for iron deficiency in female athletes at NCAA Division I
      A schools is not a routine procedure and, for those who do screen, variability
      exists in the criteria for diagnosis, as well as in treatment protocols. Standard
      protocols for assessment and treatment of iron deficiency in female athletes need
      to be developed and implemented.

PMID- 14669929
TI  - Case study of training, fitness, and nourishment of a dog driver during the
      Iditarod 1049-mile dogsled race.
AB  - The purpose of the present case study was threefold: (a) to estimate intake and
      expenditure of a dog driver (musher) while participating in the Iditarod, (b) to
      determine the hydration status of the musher at the completion of the event, and
      (c) to evaluate training related changes in aerobic capacity and body composition
      of a long-distance dog sled driver in preparation for and following completion of
      a 1049-mile (1692-km) sled dog race. Actual energy intake during the Iditarod
      Sled Dog Race was estimated at 8,921 kilojoules (kJ) per day. Nutrient intake
      expressed as percentage kJ of total energy (14%, 44% and 42% for protein,
      carbohydrates, and fat, respectively). Weight loss of .72 kg of body weight
      indicated an energy deficit of 1819 kJ per day during the race. Total energy
      needs per day were calculated to be 10,740 kJ/day. An increase in hematocrit and
      hemoglobin during the race may indicate dehydration during the event. There was
      an improvement in aerobic fitness during on-snow training as determined by
      ventilatory threshold and VO2peak data. Fat-free mass was maintained during
      training (46.4 kg), with a concomitant decrease in fat (2.4 kg). Fat-free mass
      was also maintained during the 12-day race.

PMID- 14669930
TI  - Effect of alpha-lipoic acid combined with creatine monohydrate on human skeletal
      muscle creatine and phosphagen concentration.
AB  - Alpha-lipoic acid has been found to enhance glucose uptake into skeletal muscle
      in animal models. Studies have also found that the co-ingestion of carbohydrate
      along with creatine increases muscle creatine uptake by a process related to
      insulin-stimulated glucose disposal. The purpose of this study was to determine
      the effect of alpha-lipoic acid on human skeletal muscle creatine uptake by
      directly measuring intramuscular concentrations of creatine, phosphocreatine, and
      adenosine triphosphate when creatine monohydrate was co-ingested with alpha
      lipoic acid. Muscle biopsies were acquired from the vastus lateralis m. of 16
      male subjects (18-32 y) before and after the experimental intervention. After the
      initial biopsy, subjects ingested 20 g x d(-1) of creatine monohydrate, 20 g x d(
      1) of creatine monohydrate + 100 g x d(-1) of sucrose, or 20 g x d(-1) of
      creatine monohydrate + 100 g x d(-1) of sucrose + 1000 mg x d(-1) of alpha-lipoic
      acid for 5 days. Subjects refrained from exercise and consumed the same balanced
      diet for 7 days. Body weight increased by 2.1% following the nutritional
      intervention, with no differences between the groups. There was a significant
      increase in total creatine concentration following creatine supplementation, with
      the group ingesting alpha-lipoic acid showing a significantly greater increase (p
      < .05) in phosphocreatine (87.6 --> 106.2 mmol x kg(-1) dry mass [dm]) and total
      creatine (137.8 --> 156.8 mmol x kg(-1) dm). These findings indicate that co
      ingestion of alpha-lipoic acid with creatine and a small amount of sucrose can
      enhance muscle total creatine content as compared to the ingestion of creatine
      and sucrose or creatine alone.

PMID- 14669931
TI  - Pre- and post-season dietary intake, body composition, and performance indices of
      NCAA division I female soccer players.
AB  - Little published data describe the dietary and physiological profiles of
      intercollegiate female soccer players; therefore, the purpose of this
      investigation was to report baseline dietary data, anthropometrics, and
      performance indices of soccer women during rigorous pre-season training (2
      sessions/day) and then during the post-competitive season. Members of a NCAA
      Division I women's soccer squad completed 3-day diet records, anthropometrics,
      and physical tests, including VO2peak. Average body mass was 62 kg with 16% body
      fat, and no significant pre to post differences were observed. Total energy,
      carbohydrate (CHO), protein, and fat intakes were significantly greater during
      the pre-season. Pre-season energy intake met the DRI for females with an "active"
      lifestyle (37 kcal/kg). While CHO intake failed to meet minimum recommendations
      to promote glycogen repletion (7-10 g/kg), protein and fat intakes were above
      minimum recommendations. Pre- and post-season intakes of several micronutrients
      were marginal (<75% of the DRI) including vitamin E, folate, copper, and
      magnesium. VO2peak significantly improved from pre- to post-season (42 and 50
      ml/kg/min). In this study female soccer players appeared to meet caloric needs
      during periods of training but failed to meet minimum CHO and micronutrient
      recommendations. Foods higher in protein and fat displaced more CHO-rich and
      nutrient-dense foods within athletes' energy requirements and satiety limits.

PMID- 14669932
TI  - Dietary supplementation practices of Singaporean athletes.
AB  - The supplementation practices of elite athletes in Singapore were studied using
      an anonymous questionnaire. Information was sought on not only the type of
      supplements used but also dosage, rationale for use, and other factors that might
      influence supplement use including selected demographic parameters and sources of
      information relating to supplements. Data was collected from 160 athletes across
      a spectrum of 30 sports. Use of supplements was widespread, with 77% of
      respondents acknowledging use of at least 1 product. Respondents ingested a total
      of 59 different supplements, with each athlete using on average 3.6 +/- 0.3
      different products. Sports drinks, caffeine, vitamin C, multivitamin/mineral
      supplements, and essence of chicken were some of the most commonly ingested
      products, confirming that while vitamin/mineral supplements are popular, sports
      supplements and traditional/herbal preparations were also well accepted.
      Respondents preferred to source information pertaining to supplements from
      "significant others" and other readily accessible sources. A small number of
      respondents acknowledged the use of International Olympic Committee (IOC) banned
      or restricted substances, highlighting the need for athletes to consult sports
      medicine professionals with specialist knowledge of dietary supplements in
      advance of initiating any supplementation regime.

PMID- 14669933
TI  - One hour cycling performance is not affected by ingested fluid volume.
AB  - This study investigated the effect of differing fluid volumes consumed during
      exercise, on cycle time-trial (TT) performance conducted under thermoneutral
      conditions (20 degrees C, 70% RH). Ten minutes after consuming a bolus of 6 ml x
      kg(-1) body mass (BM) of a 6.4% CHO solution and immediately following a warm-up,
      8 male cyclists undertook a 1-h self-paced TT on 4 separate occasions. During a
      "familiarization" trial, subjects were given three 5-min periods (15-20 min, 30
      35 min, and 45-50 min) to consume fluid ad libitum. Thereafter subjects
      undertook, in random order, trials consuming high (HF), moderate (MF), or low
      fluid (LF) volumes, where 300, 150, and 40 ml of fluid were consumed at 15, 30,
      and 45 min of each trial, respectively, and total CHO intake was maintained at
      57.6 g. During exercise, power output and heart rate were monitored continuously,
      whilst stomach fullness was rated every 10 min. Additionally, BM loss and BM loss
      corrected for fluid intake was calculated during each trial. At 40, 50, and 60
      min differences in ratings of stomach fullness were found between trials (LF vs.
      HF and MF vs. HF). There were however no differences in performance or
      physiological variables (heart rate or BM loss) between trials. These results
      indicate that when a pre-exercise CHO bolus is consumed, there is no effect of
      subsequent consumption of different fluid volumes when trained cyclists undertake
      a 1-h performance task in a thermoneutral environment.

PMID- 14669934
TI  - Copper status of collegiate female athletes involved in different sports.
AB  - Copper status was assessed in 70 female collegiate athletes aged 18 to 25 years
      participating in cross country track, tennis, softball, swimming, soccer,
      basketball, and gymnastics during the 2000-2001 season. A group of 8 college-aged
      females, 20 to 23 years of age, who were not collegiate athletes, served as
      controls. Mean copper intakes including supplements did not differ significantly
      among the controls and athletic teams. Mean copper intakes including supplements
      as micrograms/day and percent recommended dietary allowance (RDA) were as
      follows: controls 1071 +/- 772 microg (119 +/- 86%), cross country track 1468 +/-
      851 microg (163 +/- 95%), tennis 1099 +/- 856 microg (122 +/- 95%), softball 654
      +/- 420 microg (73 +/- 47%), swimming 1351 +/- 1060 g (150 +/- 118%), soccer 695
      +/- 368 microg (77 +/- 41%), and gymnastics 940 +/- 863 microg (104 +/- 96%).
      Forty-one percent of athletes and 29% of controls failed to consume two thirds of
      the RDA for copper. Mean serum copper and ceruloplasmin concentrations were
      within the normal range and did not differ significantly among the controls (117
      +/- 22 microg/dl, 445 +/- 122 mg/L) and cross country track (98 +/- 17 microg/dl,
      312 +/- 59 mg/L), tennis (140 +/- 84 microg/dl, 424 +/- 244 mg/L), softball (95
      +/- 30 microg/dl, 310 +/- 77 mg/L), swimming (98 +/- 25 microg/dl, 312 +/- 40
      mg/L), soccer (93 +/- 15 microg/dl, 324 +/- 54 mg/ L), basketball (85 +/- 10
      microg/dl, 280 +/- 62 mg/L), and gymnastics (96 +/- 21 microg/dl, 315 +/- 68
      mg/L) teams. Copper status of female collegiate athletes appears to be adequate
      in this cross-sectional assessment.

PMID- 14669935
TI  - Accuracy of three dry-chemistry methods for lipid profiling and risk factor
      classification.
AB  - The purpose of this project was to determine the accuracy in lipids measurement
      and risk factor classification using Reflotron, Cholestech, and Ektachem DT-60
      dry-chemistry analyzers. Plasma and capillary venous blood from fasting subjects
      (n = 47) were analyzed for total cholesterol (TC), high density lipoprotein (HDL
      C), and triglycerides (TG) using these analyzers and a CDC certified laboratory.
      Accuracy was evaluated by comparing the results of each portable analyzer against
      the CDC reference method. One-way ANOVAs were performed for TC, HDL-C, and TG
      between all portable analyzers and the reference method. Chi-square was used for
      risk classification (2001 NIH Guidelines). Compared to the reference method, the
      Ektachem and Reflotron provided significantly lower values for TC (p < .05). In
      addition, the Cholestech and Ektachem values for HDL-C were higher than the CDC
      (p < .05). The Reflotron and Cholestech provided higher values of TG than the CDC
      (p < .05). Chi-squares analyses for risk classification were not significant (p >
      .45) between analyzers. According to these results, the Ektachem and Cholestech
      analyzers met the current NCEP III guidelines for accuracy in measurement of TC,
      while only Ektachem met guidelines for TG. All 3 analyzers provided a good
      overall risk classification; however, values of HDL-C should be only used for
      screening purposes.

PMID- 14669936
TI  - Antioxidant supplementation enhances neutrophil oxidative burst in trained
      runners following prolonged exercise.
AB  - The influence of an antioxidant vitamin supplement on immune cell response to
      prolonged exercise was determined using a randomized, double-blind, placebo
      controlled, cross-over study. Twelve healthy endurance subjects (n = 6 male, n =
      6 female; mean +/- SD for age, 30.1 +/- 6.2 yr; height, 1.76 +/- 7 m; body mass,
      72.2 +/- 10.2 kg; VO2max, 63.7 +/- 12 ml x kg(-1) x min(-1)) participated in the
      study. Following a 3-week period during which subjects ingested a multivitamin
      and -mineral complex sufficient to meet the recommended daily allowance, they
      took either a placebo or an antioxidant vitamin supplement (containing 18 mg beta
      carotene, 900 mg vitamin C, and 90 mg vitamin E) for 7 days prior to a 2-h
      treadmill run at 65% VO2max. Blood samples were drawn prior to and immediately
      following exercise. These were analyzed for neutrophil oxidative burst activity,
      cortisol and glucose concentrations, and white blood cell counts, as well as
      serum anti-oxidant vitamin concentrations. Plasma vitamin C, vitamin E, and beta
      carotene concentrations significantly increased following 7-day supplementation
      (p < .05). In comparison to the placebo group, neutrophil oxidative burst was
      significantly higher following exercise (p < .05), but no differences were found
      in any other parameter following the 7-day supplementation period. Although the
      impact of exercise on neutrophil function is multifactorial, our data suggest
      that antioxidant supplementation may be of benefit to endurance athletes for the
      maintenance of this particular function of the innate immune system following the
      7-day supplementation period.

PMID- 14669938
TI  - The effect of resistance exercise on the thermic effect of food.
AB  - PURPOSE: The thermic effect of food (TEF) is the increment in energy expenditure
      above resting metabolic rate associated with the cost of absorption and
      processing of food for storage. Previous studies have shown that TEF is enhanced
      by aerobic endurance exercise of sufficient duration and intensity. The purpose
      of this study was to determine if a similar effect occurs with a single bout of
      resistance exercise (weightlifting). METHODS: VO2 was measured in 9 healthy
      volunteers (3 males and 6 females) for 2 hours after ingestion of a 2760 kJ (660
      kcal) carbohydrate meal with and without prior completion of a resistance
      training regimen (2 sets of 10 repetitions of 10 different exercises). RESULTS:
      The meal caused an immediate and persistent thermic effect in both the control
      and the exercise trial. Mean oxygen consumption over baseline increased 20% in
      the control trial and 34% in the exercise trial. TEF calculated from VO2 and RER
      (total area under the response curve above baseline) was 73% greater in the
      exercise trial compared with the control trial (159 +/- 18 vs. 92 +/- 14 KJ/2
      hrs, p < .02). CONCLUSION: These results indicate that TEF in response to a
      carbohydrate meal is enhanced following a single bout of resistance exercise.

PMID- 14669937
TI  - Effect of a carbohydrate-protein supplement on endurance performance during
      exercise of varying intensity.
AB  - Increasing the plasma glucose and insulin concentrations during prolonged
      variable intensity exercise by supplementing with carbohydrate has been found to
      spare muscle glycogen and increase aerobic endurance. Furthermore, the addition
      of protein to a carbohydrate supplement will enhance the insulin response of a
      carbohydrate supplement. The purpose of the present study was to compare the
      effects of a carbohydrate and a carbohydrate-protein supplement on aerobic
      endurance performance. Nine trained cyclists exercised on 3 separate occasions at
      intensities that varied between 45% and 75% VO2max for 3 h and then at 85% VO2max
      until fatigued. Supplements (200 ml) were provided every 20 min and consisted of
      placebo, a 7.75% carbohydrate solution, and a 7.75% carbohydrate/1.94% protein
      solution. Treatments were administered using a double-blind randomized design.
      Carbohydrate supplementation significantly increased time to exhaustion
      (carbohydrate 19.7 +/- 4.6 min vs. placebo 12.7 +/- 3.1 min), while the addition
      of protein enhanced the effect of the carbohydrate supplement (carbohydrate
      protein 26.9 +/- 4.5 min, p < .05). Blood glucose and plasma insulin levels were
      elevated above placebo during carbohydrate and carbohydrate-protein
      supplementation, but no differences were found between the carbohydrate and
      carbohydrate-protein treatments. In summary, we found that the addition of
      protein to a carbohydrate supplement enhanced aerobic endurance performance above
      that which occurred with carbohydrate alone, but the reason for this improvement
      in performance was not evident.

PMID- 14669939
TI  - Apoptosis and autoimmune disorders.
AB  - Apoptosis or programmed cell death plays a central role in regulating not only
      the development of lymphocytes but also in their homeostasis. A breakdown in
      apoptosis related signaling mechanisms could result in the development of
      autoimmune disorders. The past decade has witnessed an explosive increase in
      knowledge with respect to various apoptotic signaling pathways and their aberrant
      behavior in autoimmune disorders. Although Fas/FasL mediated signaling appears to
      be a common paradigm that has emerged from studies in various autoimmune
      disorders, examples suggesting a role for other cell death pathways have also
      surfaced. Understanding the definitive role of apoptosis in various autoimmune
      disorders is likely to define novel targets for future therapeutic intervention.

PMID- 14669940
TI  - Thyrotropin receptor autoantibodies (TSHRAbs): epitopes, origins and clinical
      significance.
AB  - Epitopes for > 95% stimulating thyrotropin receptor autoantibodies (TSHRAbs)
      causally implicated in Graves' disease (Basedow's disease or primary
      hyperthyroidism) have been identified on on the N-terminal portion of the TSHR
      extracellular domain, residues 8-165. If the stimulating TSHRAb activity is
      solely dependent on this region, it is termed homogeneous; if its activity is
      only largely related to this region, it is termed heterogeneous. The presence of
      a heterogeneous stimulating TSHRAb in a patient is associated with rapid
      responses to propylthiouracil or methimazole and may be predictive of long term
      remission with these oral immunosuppressives. Epitopes for two different Graves'
      autoantibodies that inhibit TSH binding, TSH binding inhibition immunoglobulins
      or TBIIs, have also been identified on this region of the TSHR. They do not
      increase cAMP levels, although one may activate the inositol phosphate, Ca++,
      arachidonate release signal system. The epitope of blocking TSHRAbs with the
      ability to inhibit TSH binding (TBII activity), TSH activity, and stimulating
      TSHRAb activity, and that are causally implicated in the primary hypothyroidism
      of patients with idiopathic myxedema or some patients with Hashimoto's disease
      have, in contrast, been largely identified largely on the C-terminal portion of
      the TSHR extracellular domain, residues 270-395. They have been implicated as
      important in pregnancy where they attenuate the signs and symptoms of Graves'
      hyperthyroidism. The appearance of these blocking TSHRAbs during pregnancy in
      Graves' patients might cause overt or occult hypothyroidism, with resultant
      effects on fetal development and postnatal intelligence levels. The different
      TSHRAbs can exist in the same patient at any moment in time, potentially making
      disease expression a sum of their activities. Assays taking advantage of the
      epitope mapping findings enable us to detect individual TSHRAbs within a single
      patient and to better understand their clinical significance.

PMID- 14669941
TI  - Autoimmune thyroid disease and pregnancy: relevance for the child.
AB  - As a group, the autoimmune thyroid diseases, including Graves' disease,
      Hashimoto's thyroiditis, and primary myxedema, are among the most common
      endocrine disorders encountered during pregnancy. Therefore, a substantial number
      of offspring will grow and develop in utero under conditions of maternal
      autoimmune thyroid disease and may be exposed to abnormal maternal thyroid
      function, maternal thyroid antibodies, and/or numerous therapeutic agents used to
      manage maternal thyroid dysfunction. This article reviews the effects that these
      various aspects of maternal autoimmune thyroid disorders can have on pregnancy
      outcome, as well as on the physical growth, neuropsychological development, and
      thyroid status of the developing fetus and neonate.

PMID- 14669942
TI  - Cytokines in thyroid autoimmunity.
AB  - The role of cytokines in the pathogenesis of autoimmune thyroid disease (ATD) has
      been extensively investigated over the past years. In patients with ATD, these
      molecules can be found in both the thyroid and sites of extrathyroidal
      complications of the disease. Cytokines can affect the autoimmune process through
      a number of mechanisms including recruitment of inflammatory cells and
      upregulation of molecules essential for perpetuation of the inflammatory response
      in the affected site. In addition, cytokines can interfere with thyroid hormone
      synthesis, implicating them directly in thyroid dysfunction found in ATD
      patients. Also, these molecules can modulate the function of cells in orbital
      tissue, which results in localised oedema, indicating a central role for
      cytokines in the development of proptosis, the cardinal feature of thyroid
      associated ophthalmopathy.

PMID- 14669943
TI  - Monoclonal antibodies to thyroid specific autoantigens.
AB  - Monoclonal antibody (MAbs) is a powerful and essential tool to perform studies
      concerning antigens and antibodies at molecular level. MAbs to major thyroid
      specific autoantigens, thyroglobulin (Tg), thyroid peroxidase (TPO) and TSH
      receptor (TSHR), have been prepared and applied for a variety of investigations
      including the structure of antigens and antibodies, the expression of antigens,
      the epitopes of antibodies, the functional regions of antigens, mutated antigens
      in congenital diseases, and clinical applications to diagnosis of various thyroid
      diseases. Recently, sodium iodide symporter (NIS) was identified and became a
      potential thyroid autoantigen related to autoimmune thyroid disease, although few
      MAbs to NIS have been prepared. In this manuscript, I primarily focus on studies
      concerning MAbs to three major thyroid specific autoantigens, Tg, TPO and TSHR,
      and summarize studies using the mAbs.

PMID- 14669944
TI  - The contribution of immune regulatory and thyroid specific genes to the etiology
      of Graves' and Hashimoto's diseases.
AB  - The autoimmune thyroid diseases (AITD) are complex diseases which are caused by
      an interaction between susceptibility genes and environmental triggers. Genetic
      susceptibility in combination with external factors (e.g. dietary iodine) are
      believed to initiate the autoimmune response to thyroid antigens. Abundant
      epidemiological data, including family and twin studies, point to a strong
      genetic influence on the development of AITD. Various techniques have been
      employed to identify the genes contributing to the etiology of AITD, including
      candidate gene analysis and whole genome screening. These studies have enabled
      the identification of several loci (genetic regions) that are linked with AITD,
      and in some of these loci putative AITD susceptibility genes have been
      identified. Some of these genes/loci are unique to Graves' disease (GD) and
      Hashimoto's thyroiditis (HT) and some are common to both diseases, indicating
      that there is a shared genetic susceptibility to GD and HT. The putative GD and
      HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4)
      and thyroid specific genes (e.g. TSHR, Tg). Most likely these loci interact and
      their interactions may influence disease phenotype and severity.

PMID- 14669945
TI  - Animal models of Graves' hyperthyroidism.
AB  - An animal model of Graves' disease (GD) will help us to clearly understand the
      role of thyroid-stimulating hormone receptor (TSHR)-specific T cells and TSHR-Abs
      during the development of GD and to develop TSHR-specific immunotherapy. This
      review focuses on four different recent approaches towards the development of an
      animal model of GD. These approaches are: (1) Immunization of AKR/N mice with
      fibroblasts coexpressing syngeneic major histocompatibility complex (MHC) class
      II and TSHR. (2) Immunization of selected strains of mice with an expression
      vector containing TSHR cDNA. (3) Immunization of BALB/c mice with syngeneic M12
      cells or xenogenic HEK-293 cells expressing full-length or extracellular domain
      of TSHR (ETSHR). (4) Injection of adenovirus-expressing TSHR into BALB/c mice.

PMID- 14669946
TI  - Modulation of dendritic cell function and cytokine production to prevent thyroid
      autoimmunity.
AB  - Understanding autoimmune thyroid diseases provides an unique perspective on the
      role of various components of the immune system in the pathogenesis of organ
      specific autoimmune diseases, whether the effector mechanism involves
      autoantibodies or T cells. Hashimoto's thyroiditis (HT) is largely mediated by
      thyroglobulin specific T cells, while Graves' disease (GD) is mediated by
      thyrotropin receptor specific autoantibodies. HT is characterized by thyroid
      destruction mediated by infiltrating or activated resident immune cells through a
      variety of mechanisms. In contrast GD is characterized by excessive production of
      thyroid hormone with little or no glandular destruction. Irrespective of the
      effector mechanism involved, dendritic cells (DCs) are required for the induction
      of an efficient primary response and thus are the first cells involved in an
      autoimmune response. DCs also provide the essential link between the innate and
      the adaptive immune system through co-stimulatory molecules and the production of
      cytokines and chemokines. Furthermore, inflammatory cytokines also appear to
      enhance the susceptibility of thyrocytes to apoptosis. In this review, we discuss
      the role of innate immunity in initiating an adaptive autoimmune response against
      the thyroid. We will explore the role of different mechanisms involved in
      breaking self-tolerance to thyroid antigens. Further, we will discuss recent
      developments in the development of experimental therapeutics against AITD.

PMID- 14669947
TI  - HLA and H2 class II transgenic mouse models to study susceptibility and
      protection in autoimmune thyroid disease.
AB  - Using single H2 and HLA class II transgenic mice, in the absence of endogenous H2
      class II molecules, we have studied the permissiveness of class II molecules for
      experimental autoimmune thyroiditis (EAT). Resistant strains expressing
      susceptible class II molecules, H2Ak or HLA-DR3, developed EAT, clearly
      demonstrating the importance of class II gene inheritance. Polymorphism for HLA
      DRB1 was observed, as DR3, but not DR2 or DR4, molecules were permissive for EAT
      induction with either mouse (m) or human (h) thyroglobulin (Tg). HLA-DQ
      polymorphism was also detectable, as hTg-induced EAT developed in DQ8+, but not
      DQ6+, mice. Class II gene interactions leading to reduced EAT severity were
      observed in H2 transgenic mice, when H2E transgene was expressed in H2A+ mice or
      H2A molecules were introduced into our novel H2A- E+ transgenic model. Similarly,
      in DR3+ mice, only the DQ8 transgene reduced EAT severity, depending on both
      background genes (C57BL/10 or NOD) and Tg species. Based on computer-predicted,
      class II-binding motifs, potential pathogenic Tg peptides, either unique to hTg
      (H2A- E+ model) or shared between mTg and hTg (HLA-DR3+ model), were identified.
      We have also developed a Graves' disease model by immunizing DR3+ mice with TSH
      receptor DNA. Thus, transgenic models are excellent tools to study human
      autoimmune thyroid diseases in the context of murine EAT.

PMID- 14669948
TI  - NKT cell regulation of autoimmune thyroiditis.

PMID- 14669949
TI  - The putative role of fibroblasts in the pathogenesis of Graves' disease: evidence
      for the involvement of the insulin-like growth factor-1 receptor in fibroblast
      activation.
AB  - Graves' disease when fully expressed affects the thyroid gland and connective
      tissues of the orbit and pretibium. While the glandular disease is relatively
      well-characterized, the pathogenesis of the orbital and dermal components remains
      enigmatic. In the following article, we review some of the evidence suggesting
      that fibroblast activation in Graves' disease might play an integral role in the
      tissue remodeling associated with ophthalmopathy. The thyrotropin receptor (TSHR)
      is expressed at low levels in several connective tissue depots and by their
      derivative fibroblasts, including those from the orbit. Little direct evidence
      currently links extra-thyroidal TSHR expression with Graves' disease. Very recent
      observations now implicate the insulin-like growth factor-1 receptor (IGF-1R) as
      a fibroblast activating antigen. When immunoglobulins from patients with the
      disease, with or without clinical ophthalmopathy, bind IGF-1R on the surface of
      fibroblasts, the receptor becomes activated and upregulates the expression of two
      T lymphocyte chemoattractants, IL-16 and RANTES. Thus, IGF-1R may represent a
      second self-antigen with a pathogenic role in extra-thyroidal Graves' disease.

PMID- 14669950
TI  - Physiological relevance of thyroid stimulating hormone and thyroid stimulating
      hormone receptor in tissues other than the thyroid.
AB  - Decades of research have provided strong evidence for a reciprocal relationship
      between the immune system and hormones of the hypothalamus-pituitary-thyroid
      (HPT) axis. Thyroid stimulating hormone (TSH), in particular, has been shown to
      have a variety of immune-regulating cytokine-like activities that can influence
      the outcome of T cell development in the thymus and intestine, and can affect the
      magnitude of antibody and cell-mediated responses of peripheral lymphocytes.
      Production of TSH and the expression of the TSH receptor are widely but
      selectively distributed across many different types of hematopoietic cells in the
      bone marrow, as well as among subsets of dendritic cells, monocytes and
      lymphocytes in the spleen and lymph nodes. In addition to their role in immunity,
      the involvement of TSH-producing hematopoietic cells in the microregulation of
      thyroid hormone activity represents a novel and potentially important aspect of
      the TSH-mediated immune-endocrine circuit.

PMID- 14669951
TI  - The cryptic self in thyroid autoimmunity: the paradigm of thyroglobulin.
AB  - Recent studies have increased the number of known thyroiditogenic sites in
      thyroglobulin (Tg) to thirteen. These sites contain T-cell epitopes and are
      scattered throughout Tg, with nine of them localized toward the carboxyl terminal
      third of the molecule. So far, no pathogenic determinant has been found to be
      dominant, i.e. to be readily and consistently generated in extrathyroidal antigen
      presenting cells (APC) following processing of intact Tg in vivo and in vitro.
      However, certain conditions, such as internalization of Tg-antibody complexes or
      enhanced iodination of Tg, have been described to promote generation of cryptic
      pathogenic peptides in APC, in vitro. These findings support the view that post
      translational events can "unmask the cryptic self' and suggest mechanisms that
      may contribute to the pathogenesis of thyroiditis.

PMID- 14669952
TI  - Aberrancies in antigen-presenting cells and T cells in autoimmune thyroid
      disease. A role in faulty tolerance induction.
AB  - Various thyrocyte, monocyte, macrophage, DC and T cell abnormalities exist in the
      animal models of spontaneously developing autoimmune thyroiditis and in patients
      with autoimmune thyroid disease. An aberrant interaction between such abnormal
      thyrocytes, abnormal professional antigen-presenting cells (APC) and abnormal T
      cells forms the basis for the atypical autoimmune reaction targeting thyroid
      antigens. In the atypical interaction more than one gene and various
      environmental factors are involved. The genetic and environmental factors must
      act together to induce full-blown disease. Although there is a general blueprint
      for the development of destructive autoimmune thyroiditis, thyrocyte and immune
      cell abnormalities differ between the various animal models and the various forms
      of autoimmune thyroid disease (either associated with type 1 diabetes, associated
      with bipolar disorder or not associated). This tells us that there are different
      etio-pathogenic forms of destructive autoimmune thyroiditis. Whether such
      heterogeneity is also the case for the etio-pathogenesis of Graves' disease
      remains unknown. Animal models of spontaneously developing Graves' disease would
      be helpful in unraveling this question. If indeed there are various etio
      pathogenic routes in different patients that lead to destructive autoimmune
      thyroiditis, then tailor-made therapeutic approaches need to be carried out in
      attempts to correct the underlying immune abnormalities in individual patients or
      to prevent the development of destructive autoimmune thyroiditis in individuals
      at risk. While in some forms of destructive autoimmune thyroiditis (f.i. those
      associated with bipolar disorder) immune suppression should be the first choice
      of intervention, other forms (f.i. those associated with type 1 diabetes) may
      benefit from immune stimulation in certain pre-stages of the disease (to restore
      f.i. the faulty APC function characteristic of this condition). Obviously a more
      precise determination of the spectrum of cell-mediated immune abnormalities is
      required in individual cases of destructive autoimmune thyroiditis, before
      therapies that aim at correcting the immune abnormalities can be tested
      successfully.

PMID- 14669953
TI  - Polarized distribution of intracellular components by class V myosins in
      Saccharomyces cerevisiae.
AB  - The budding yeast Saccharomyces cerevisiae has three classes of myosins
      corresponding to three actin structures: class I myosin for endocytic actin
      structure, actin patches; class II myosin for contraction of the actomyosin
      contractile ring around the bud neck; and class V myosin for transport along a
      cable-like actin structure (actin cables), extending toward the growing cortex.
      Myo2p and Myo4p constitute respective class V myosins as the heavy chain and,
      like class V myosins in other organisms, function as actin-based motors for
      polarized distribution of organelles and intracellular molecules. Proper
      distribution of organelles is essential for autonomously replicating organelles
      that cannot be reproduced de novo, and is also quite important for other
      organelles to ensure their efficient segregation and proper positioning, even
      though they can be newly synthesized, such as those derived from endoplasmic
      reticulum. In the budding yeast, microtubule-based motors play limited roles in
      the distribution. Instead, the actin-based motor myosins, especially Myo2p, play
      a major role. Studies on Myo2p have revealed a wide variety of Myo2p cargo and
      Myo2p-interacting proteins and have established that Myo2p interacts with cargo
      and transfers it along actin cables. Moreover, recent findings suggest that Myo2p
      has another way to distribute cargo in that Myo2p conveys the attaching cargo
      along the actin track. Thus, the myosin have "dual paths" for distribution of a
      cargo. This dual path mechanism is proposed in the last section of this review.

PMID- 14669954
TI  - Deubiquitinating enzymes: their roles in development, differentiation, and
      disease.
AB  - The ubiquitin-mediated proteolysis pathway has come a long way in the past
      decade. At first thought to be an unglamorous garbage dump for damaged proteins,
      the ubiquitin pathway has been shown to regulate virtually everything that occurs
      in the cell. Deubiquitinating enzymes, which cleave ubiquitin-protein bonds, are
      the largest group of enzymes in the pathway, yet they are the least well
      understood. Deubiquitinating enzymes have two kinds of functions: housekeeping
      and regulatory. The housekeeping enzymes facilitate the proteolytic pathway. By
      contrast, the regulatory enzymes control the ubiquitination of specific protein
      substrates; their relationship to ubiquitination is analgous to that of
      phosphatases with respect to phosphorylation. Here, I review the current state of
      knowledge of the deubiquitinating enzymes. I focus particularly on the known
      regulatory enzymes, and also on the housekeeping enzymes that are implicated in
      development of disease.

PMID- 14669955
TI  - Mechanisms and control of nutrient uptake in plants.
AB  - This review is a distillation of the vast amount of physiological and molecular
      data on plant membrane transport, to provide a concise overview of the main
      processes involved in the uptake of mineral nutrients in plants. Emphasis has
      been placed on transport across the plasma membrane, and on the primary uptake
      from soil into roots, or in the case of aquatic plants, from their aqueous
      environment. Control of uptake has been mainly considered in terms of local
      effects on the rate of transport and not in terms of long-distance signaling. The
      general picture emerging is of a large array of membrane transporters, few of
      which display any strong selectivity for individual nutrients. Instead, many
      transporters allow low-affinity uptake of several different nutrients. These
      features, plus the huge number of potential transporter genes that has been
      revealed by sequencing of plant genomes, raise some interesting questions about
      their evolution and likely function.

PMID- 14669956
TI  - Interstitial cells in the musculature of the gastrointestinal tract: Cajal and
      beyond.
AB  - Expression of the receptor tyrosine kinase KIT on cells referred to as
      interstitial cells of Cajal (ICC) has been instrumental during the past decade in
      the tremendous interest in cells in the interstitium of the smooth muscle layers
      of the digestive tract. ICC generate the pacemaker component (electrical slow
      waves of depolarization) of the smooth musculature and are involved in
      neurotransmission. By integration of ICC functions, substantial progress has been
      made in our understanding of the neuromuscular control of gastrointestinal
      motility, opening novel therapeutic perspectives. In this article, the
      ultrastructure and light microscopic morphology, as well as the functions and the
      development of ICC and of neighboring fibroblast-like cells (FLC), are critically
      reviewed. Directions for future research are considered and a unifying concept of
      mesenchymal cells, either KIT positive (the "ICC") or KIT negative "non-Cajal"
      (including the FLC and possibly also other cell types) cell types in the
      interstitium of the smooth musculature of the gastrointestinal tract, is
      proposed. Furthermore, evidence is accumulating to suggest that, as postulated by
      Santiago Ramon y Cajal, the concept of interstitial cells is not likely to be
      restricted to the gastrointestinal musculature.

PMID- 14669957
TI  - New aspects of gravity responses in plant cells.
AB  - Plants show two distinct responses to gravity: gravity-dependent morphogenesis
      (gravimorphogenesis) and gravity resistance. In gravitropism, a typical mechanism
      of gravimorphogenesis, gravity is utilized as a signal to establish an
      appropriate form. The response has been studied in a gravity-free environment,
      where plant seedlings were found to perform spontaneous morphogenesis, termed
      automorphogenesis. Automorphogenesis consists of a change in growth direction and
      spontaneous curvature in dorsiventral directions. The spontaneous curvature is
      caused by a difference in the capacity of the cell wall to expand between the
      dorsal and the ventral sides of organs, which originates from the inherent
      structural anisotropy. Gravity resistance is a response that enables the plant to
      develop against the gravitational force. To resist the force, the plant
      constructs a tough body by increasing the cell wall rigidity that suppresses
      growth. The mechanical properties of the cell wall are changed by modification of
      the cell wall metabolism and cell wall environment, especially pH. In
      gravitropism, gravity is perceived by amyloplasts in statocytes, whereas gravity
      resistance may be mediated by mechanoreceptors on the plasma membrane.

PMID- 14669958
TI  - Regulation of cortical actin networks in cell migration.
AB  - The actin cytoskeleton is a primary determinant of cell shape and motility.
      Studies on actin regulatory proteins are now coupled with studies of the signal
      transduction that directs actin cytoskeleton reorganization, and we have gained
      insights into how external stimuli such as chemoattractants drive changes in
      actin cytoskeleton. Chemoattractants regulate actin regulatory proteins such as
      the Arp2/3 complex through WASP family proteins, ADF/cofilin downstream of LIM
      kinase, and various other phosphoinositide-dependent or -independent pathways.
      Through branching of actin filaments, Arp2/3 complex-dependent actin
      polymerization is suffcient to generate the force necessary for protrusion.

PMID- 14669959
TI  - The influence of altered lower-extremity kinematics on patellofemoral joint
      dysfunction: a theoretical perspective.
AB  - Although patellofemoral pain (PFP) is recognized as being one of the most common
      disorders of the lower extremity, treatment guidelines and underlying rationales
      remain vague and controversial. The premise behind most treatment approaches is
      that PFP is the result of abnormal patellar tracking and/or patellar
      malalignment. Given as such, interventions typically focus on the joint itself
      and have traditionally included strengthening the vastus medialis oblique,
      taping, bracing, soft tissue mobilization, and patellar mobilization. More
      recently, it has been recognized that the patellofemoral joint and, therefore,
      PFP may be influenced by the interaction of the segments and joints of the lower
      extremity. In particular, abnormal motion of the tibia and femur in the
      transverse and frontal planes may have an effect on patellofemoral joint
      mechanics. With this in mind, interventions aimed at controlling hip and pelvic
      motion (proximal stability) and ankle/foot motion (distal stability) may be
      warranted and should be considered when treating persons with patellofemoral
      joint dysfunction. The purpose of this paper is to provide a biomechanical
      overview of how altered lower-extremity mechanics may influence the
      patellofemoral joint. By addressing these factors, better long-term treatment
      success and prevention may be achieved.

PMID- 14669960
TI  - Management of patellofemoral pain targeting hip, pelvis, and trunk muscle
      function: 2 case reports.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe an alternative treatment
      approach for patellofemoral pain. BACKGROUND: Weakness of the hip, pelvis, and
      trunk musculature has been hypothesized to influence lower-limb alignment and
      contribute to patellofemoral pain. Two patients who had a chief complaint of
      patellofemoral pain and demonstrated lack of control of the hip in the frontal
      and transverse planes during functional movements were treated with an exercise
      program targeting the hip, pelvis, and trunk musculature. METHODS AND MEASURES:
      The patients presented in these 2 case reports did not exhibit obvious patellar
      malalignment or tracking problems; however, on qualitative assessment, both
      demonstrated excessive hip adduction, internal rotation, and knee valgus during
      gait and while performing a step-down maneuver. In addition, both patients
      exhibited weakness of the hip abductors, extensors, and external rotators, as
      demonstrated by hand-held dynamometry testing. Treatment in both cases occurred
      over a 14-week period and focused on recruitment and endurance training of the
      hip, pelvis, and trunk musculature. Functional status, pain, muscle force
      production, as well as subjective and objective assessment of lower-extremity
      kinematics during gait and a step-down maneuver were assessed preintervention and
      postintervention. RESULTS: Both patients experienced a significant reduction in
      patellofemoral pain, improved lower-extremity kinematics during dynamic testing,
      and were able to return to their original levels of function. Gluteus medius
      force production improved by 50% in patient A and 90% in patient B, while gluteus
      maximus force production improved 55% in patient A and 110% in patient B.
      Objective kinematic improvements in the step-down task also were demonstrated in
      patient A. CONCLUSION: Assessment and treatment of the hip, pelvis, and trunk
      musculature should be considered in the rehabilitation of patients who present
      with patellofemoral pain and demonstrate abnormal lower-extremity kinematics.

PMID- 14669961
TI  - The role of foot orthoses as an intervention for patellofemoral pain.
AB  - Foot orthoses often are prescribed for patients with patellofemoral pain. The
      purpose of this clinical commentary is to review the theoretical and research
      basis that might support this intervention and to provide our own clinical
      experience in providing foot orthoses for these patients. Literature is reviewed
      regarding (1) the effects of foot orthoses on pain and function, (2) the
      relationship between foot and lower-extremity/patellofemoral joint mechanics, (3)
      the effects of foot orthoses on lower-extremity mechanics, and (4) the effects of
      foot orthoses on patellofemoral joint position. The literature and our own
      clinical experience suggest that patients with patellofemoral pain may benefit
      from foot orthoses if they also demonstrate signs of excessive foot pronation
      and/or a lower-extremity alignment profile that includes excessive lower
      extremity internal rotation during weight bearing and increased Q angle. The
      mechanism for foot orthoses having a positive effect on pain and function for
      these patients may include (1) a reduction in internal rotation of the lower
      extremity; (2) a reduction in Q angle; (3) reduced laterally-directed soft tissue
      forces from the patellar tendon, the quadriceps tendon, and the iliotibial band;
      and (4) reduced patellofemoral contact pressures and altered patellofemoral
      contact pressure mapping. Foot orthoses may be a valuable adjunct to other
      intervention strategies for patients who present with the previously stated
      structural alignment profile.

PMID- 14669962
TI  - Hip strength in females with and without patellofemoral pain.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVES: To determine if females with anterior
      knee pain are more likely to demonstrate hip abduction or external rotation
      weakness than a similar, asymptomatic, age-matched control group. BACKGROUND:
      Diminished hip strength has been implicated as being contributory to lower
      extremity malalignment and patellofemoral pain. The identification of reliable
      and consistent patterns of weakness in this population may assist health care
      professionals establish a more effective treatment plan. METHODS AND MEASURES:
      Hip abduction and external rotation isometric strength measurements were recorded
      for the injured side of 15 female subjects with patellofemoral joint pain (mean
      +/- SD age, 15.7 +/- 2.7 years; age range, 12-21 years). These were compared with
      strength measurements from the corresponding hip of 15 age-matched female control
      subjects (mean +/- SD age, 15.7 +/- 2.7 years; age range, 12-21 years). All
      strength measurements were made using hand-held dynamometers. RESULTS: Subjects
      with patellofemoral pain demonstrated 26% less hip abduction strength (P<.001)
      and 36% less hip external rotation strength (P<.001) than similar age-matched
      controls. CONCLUSIONS: The results indicate that young women with patellofemoral
      pain are more likely to demonstrate weakness in hip abduction as well as external
      rotation than age-matched women who are not symptomatic.

PMID- 14669963
TI  - Patellofemoral kinematics during weight-bearing and non-weight-bearing knee
      extension in persons with lateral subluxation of the patella: a preliminary
      study.
AB  - STUDY DESIGN: Single-group, repeated-measures design. OBJECTIVE: To compare
      patellofemoral joint kinematics during weight-bearing and non-weight-bearing knee
      extension in persons with lateral subluxation of the patella. BACKGROUND: The
      only previous study to quantify differences in patellofemoral joint kinematics
      during weight-bearing and non-weight-bearing tasks was limited in that static
      loading conditions were utilized. Differences in patellofemoral joint kinematics
      between weight-bearing and non-weight-bearing conditions have not been quantified
      during dynamic movement. METHODS AND MEASURES: Six females with a diagnosis of
      patellofemoral pain and lateral subluxation of the patella participated. Using
      kinematic magnetic resonance imaging, axial images of the patellofemoral joint
      were obtained as subjects extended their knee from 45 degrees to 0 degrees during
      non-weight-bearing (5% body weight resistance) and weight-bearing (unilateral
      squat) conditions. Measurements of patellofemoral joint relationships
      (medial/lateral patellar displacement and patellar tilt), as well as femur and
      patella rotations relative to an external reference system (ie, the image field
      of view), were obtained at 3 degrees increments during knee extension. RESULTS:
      During non-weight-bearing knee extension, lateral patellar displacement was more
      pronounced than during the weight-bearing condition between 30 degrees and 12
      degrees of knee extension, with statistical significance being reached at 27
      degrees, 24 degrees, and 21 degrees. No differences in lateral patellar tilt were
      observed between conditions (P = .065). During the weight-bearing condition,
      internal femoral rotation was significantly greater than during the non-weight
      bearing condition as the knee extended from 18 degrees to 0 degrees. During the
      non-weight-bearing condition, the amount of lateral patellar rotation was
      significantly greater than during the weight-bearing condition throughout the
      range of motion tested. CONCLUSIONS: The results of this study demonstrated that
      lateral patellar displacement was more pronounced during non-weight-bearing knee
      extension compared to weight-bearing knee extension in persons with lateral
      patellar subluxation. In addition, the results of this investigation suggest that
      the patellofemoral joint kinematics during non-weight-bearing could be
      characterized as the patella rotating on the femur, while the patellofemoral
      joint kinematics during the weight-bearing condition could be characterized as
      the femur rotating underneath the patella.

PMID- 14669964
TI  - The influence of tibial and femoral rotation on patellofemoral contact area and
      pressure.
AB  - Fixed rotation of either the femur or tibia has a significant influence on the
      patellofemoral joint contact areas and pressures. This is due to the anatomic
      asymmetry in the knee with respect to all planes, as well as the laterally
      directed force vector that naturally exists in bipedal lower-limb biomechanics.
      Specifically, femoral rotation results in an increase in patellofemoral contact
      pressures on the contralateral facets of the patella, and tibial rotation results
      in an increase in patellofemoral contact pressures on the ipsilateral facets of
      the patella. This difference can be elucidated when one considers that rotation
      of the femur is biomechanically different than rotation of the tibia. For both
      tibial and femoral rotations, the patella's distal attachment to the tibial
      tubercle influences the direction of patellar movement. The biomechanical
      evidence reviewed in this manuscript suggests that the determining factor in
      patellofemoral pathology is the derangement of normal joint mechanics. However,
      despite considerable experimental data supporting this position, there also are
      theories that suggest otherwise. This illustrates a very important point in
      patellofemoral joint pathology, where no one factor may be the sole defining
      etiology. Instead, the patellofemoral joint is one of the most complex
      diarthrodial joints in the body and there are a number of etiologic factors that
      can lead to pathology. This should be considered for developing repair and
      rehabilitation strategies.

PMID- 14669965
TI  - EFA supplementation in children with inattention, hyperactivity, and other
      disruptive behaviors.
AB  - This pilot study evaluated the effects of supplementation with PUFA on blood FA
      composition and behavior in children with Attention-Deficit/Hyperactivity
      Disorder (AD/HD)-like symptoms also reporting thirst and skin problems. Fifty
      children were randomized to treatment groups receiving either a PUFA supplement
      providing a daily dose of 480 mg DHA, 80 mg EPA, 40 mg arachidonic acid (AA), 96
      mg GLA, and 24 mg alpha-tocopheryl acetate, or an olive oil placebo for 4 mon of
      double-blind parallel treatment. Supplementation with the PUFA led to a
      substantial increase in the proportions of EPA, DHA, and alpha-tocopherol in the
      plasma phospholipids and red blood cell (RBC) total lipids, but an increase was
      noted in the plasma phospholipid proportions of 18:3n-3 with olive oil as well.
      Significant improvements in multiple outcomes (as rated by parents) were noted in
      both groups, but a clear benefit from PUFA supplementation for all behaviors
      characteristic of AD/HD was not observed. For most outcomes, improvement of the
      PUFA group was consistently nominally better than that of the olive oil group;
      but the treatment difference was significant, by secondary intent-to-treat
      analysis, on only 2 out of 16 outcome measures: conduct problems rated by parents
      (-42.7 vs. -9.9%, n = 47, P = 0.05), and attention symptoms rated by teachers (
      14.8 vs. +3.4%, n = 47, P = 0.03). PUFA supplementation led to a greater number
      of participants showing improvement in oppositional defiant behavior from a
      clinical to a nonclinical range compared with olive oil supplementation (8 out of
      12 vs. 3 out of 11, n = 33, P = 0.02). Also, significant correlations were
      observed when comparing the magnitude of change between increasing proportions of
      EPA in the RBC and decreasing disruptive behavior as assessed by the Abbreviated
      Symptom Questionnaire (ASQ) for parents (r = -0.38, n = 31, P < 0.05), and for
      EPA and DHA in the RBC and the teachers' Disruptive Behavior Disorders (DBD)
      Rating Scale for Attention (r = -0.49, n = 24, P < 0.05). Interestingly,
      significant correlations were observed between the magnitude of increase in alpha
      tocopherol concentrations in the RBC and a decrease in scores for all four
      subscales of the teachers' DBD (Hyperactivity, r = -0.45; Attention, r= -0.60;
      Conduct, r = -0.41; Oppositional/Defiant Disorder, r = -0.54; n = 24, P < 0.05)
      as well as the ASQ for teachers (r = -0.51, n = 24, P < 0.05). Thus, the results
      of this pilot study suggest the need for further research with both n-3 FA and
      vitamin E in children with behavioral disorders.

PMID- 14669966
TI  - The hypotriglyceridemic effect of dietary n-3 FA is associated with increased
      beta-oxidation and reduced leptin expression.
AB  - To study the mechanisms responsible for the hypotriglyceridemic effect of marine
      oils, we monitored the effects of high dietary intake of n-3 PUFA on hepatic and
      muscular beta-oxidation, plasma leptin concentration, leptin receptor gene
      expression, and in vivo insulin action. Two groups of male Wistar rats were fed
      either a high-fat diet [28% (w/w) of saturated fat] or a high-fat diet containing
      10% n-3 PUFA and 18% saturated fat for 3 wk. The hypotriglyceridemic effect of n
      3 PUFA was accompanied by increased hepatic oxidation of palmitoyl-CoA (125%, P <
      0.005) and palmitoyl-L-carnitine (480%, P < 0.005). These findings were
      corroborated by raised carnitine palmitoyltransferase-2 activity (154%, P <
      0.001) and mRNA levels (91%, P < 0.01) as well as by simultaneous elevation of
      hepatic peroxisomal acyl-CoA oxidase activity (144%, P < 0.01) and mRNA content
      (82%, P < 0.05). In contrast, hepatic carnitine palmitoyltransferase-1 activity
      remained unchanged despite a twofold increased mRNA level after n-3 PUFA feeding.
      Skeletal muscle FA oxidation was less affected by dietary n-3 PUFA, and the
      stimulatory effect was found only in peroxisomes. Dietary intake of n-3 PUFA was
      followed by increased acyl-CoA oxidase activity (48%, P < 0.05) and mRNA level
      (83%, P < 0.05) in skeletal muscle. The increased FA oxidation after n-3 PUFA
      supplementation of the high-fat diet was accompanied by lower plasma leptin
      concentration (-38%, P < 0.05) and leptin mRNA expression (-66%, P < 0.05) in
      retroperitoneal adipose tissue, and elevated hepatic mRNA level for the leptin
      receptor Ob-Ra (140%, P < 0.05). Supplementation of the high-fat diet with n-3
      PUFA enhanced in vivo insulin sensitivity, as shown by normalization of the
      glucose infusion rate during euglycemic hyperinsulinemic clamp. Our results
      indicate that the hypotriglyceridemic effect of dietary n-3 PUFA is associated
      with stimulation of FA oxidation in the liver and to a smaller extent in skeletal
      muscle. This may ameliorate dyslipidemia, tissue lipid accumulation, and insulin
      action, in spite of decreased plasma leptin level and leptin mRNA in adipose
      tissue.

PMID- 14669967
TI  - Interactive effects of dietary palm oil concentration and water temperature on
      lipid digestibility in rainbow trout, Oncorhynchus mykiss.
AB  - An experiment was conducted to evaluate the interactive effects of dietary crude
      palm oil (CPO) concentration and water temperature on lipid and FA digestibility
      in rainbow trout. Four isolipidic diets with 0, 5, 10, or 20% (w/w) CPO, at the
      expense of fish oil, were formulated and fed to groups of trout maintained at
      water temperatures of 7, 10, or 15 degrees C. The apparent digestibility (AD) of
      the FA, measured using yttrium oxide as an inert marker, decreased with
      increasing chain length and increased with increasing unsaturation within each
      temperature regimen irrespective of CPO level fed to the fish. PUFA of the n-3
      series were preferentially absorbed compared to n-6 PUFA in all diet and
      temperature treatments. Except for a few minor FA, a significant (P < 0.05)
      interaction between diet and temperature effects on FA digestibility was found.
      Increasing dietary levels of CPO lead to significant reductions in the AD of
      saturates and, to a lesser extent, also of the other FA. Lowering water
      temperature reduced total saturated FA digestibility in trout regardless of CPO
      level. Based on the lipid class composition of trout feces, this reduction in AD
      of saturates was due in part to the increasing resistance of dietary TAG to
      digestion. Increasing CPO level and decreasing water temperature significantly
      increased TAG content in trout fecal lipids, with saturates constituting more
      than 60% of the FA composition. Total monoene and PUFA digestibilities were not
      significantly affected by water temperature in fish fed up to 10% CPO in their
      diet. The potential impact of reduced lipid and FA digestibility in cold-water
      fish fed diets supplemented with high levels of CPO on fish growth performance
      requires further research.

PMID- 14669968
TI  - Effect of orlistat on fat absorption in rats: a comparison of normal rats and
      rats with diverted bile and pancreatic juice.
AB  - Orlistat is a specific inhibitor of pancreatic and gastric lipases leading to
      decreased absorption of fat. In the present study, we measured the effect of
      orlistat on lymphatic fat transport in rats following intake of oils very
      different in FA composition and TAG structure, and compared this with the
      transport in normal rats and rats with fat malabsorption. Rats were subjected to
      cannulation of the main mesenteric lymph duct, and a feeding catheter was
      inserted into the stomach. In addition, malabsorbing rats were cannulated in the
      common bile and pancreatic duct. Emulsified safflower, fish, and randomized oils
      were administered, and lymph was collected for 24 h and analyzed for FA
      composition. Administration of 25 mg orlistat together with the dietary oils
      resulted in very small changes from baseline lymphatic transport, indicating that
      inhibition of the fat absorption was almost complete and furthermore that the
      source of fat had no influence on the inhibitory effect of orlistat. Orlistat did
      not interfere with the absorption of the hydrolysis products, since high
      absorption of sn-2 MAG and FFA (oleic acid) mixed with orlistat was observed. The
      baseline lymphatic transport in the orlistat group was higher than in the
      malabsorbing group, but this was the result of generally lower transport of
      endogenous FA in the malabsorbing group, presumably caused by the absence of bile
      FA. The transport of FA in normal rats was several-fold higher than the transport
      after orlistat addition and in malabsorbing rats. Thus, this study showed that
      orlistat inhibited fat hydrolysis, and thereby lymphatic absorption, almost
      completely independently of the fat administered.

PMID- 14669969
TI  - Dietary alpha-linolenic acid increases the n-3 PUFA content of sow's milk and the
      tissues of the suckling piglet.
AB  - alpha-Linolenic acid (18:3n-3) is a precursor to DHA (22:6n-3), which is
      essential for normal growth and development in the infant. This study was
      undertaken to assess how a raised 18:3n-3 intake in sows affects the n-3 PUFA
      content of the suckling piglet. Sows consumed a high-18:3n-3 or control diet (n-3
      PUFA/n-6 PUFA, 0.5 vs. 0.05, respectively) for 10 d prior to parturition and for
      14 d postpartum. Piglets suckled from their mothers until 14 d of age, when they
      were sacrificed. Sows consuming the high-18:3n-3 diet had 141% more 18:3n-3 and
      86% more 22:6n-3 in their milk compared to control sows. There was no difference
      in the proximate composition of the piglets. The n-3/n-6 PUFA ratio was 82%
      higher in the milk of sows consuming the high-18:3n-3 diet compared to controls.
      Piglets suckling from sows consuming the high-18:3n-3 diet had 423% more 18:3n-3
      in the carcass as well as a 460% higher n-3/n-6 PUFA ratio than controls. The
      piglets suckling from sows consuming the high-18:3n-3 diet had 333% more 18:3n-3
      and 54% more 22:6n-3 in the liver, as well as a 114% higher n-3/n-6 ratio than
      control piglets. Piglets suckling from sows consuming a high-18:3n-3 diet also
      had 24% more 22:6n-3 and a 33% higher n-3/n-6 ratio in the brain compared to
      control piglets. A high 18:3n-3 intake in the sow increases not only the 18:3n-3
      but also the 22:6n-3 content of sow's milk and the tissues of the suckling
      piglet.

PMID- 14669970
TI  - Stearic acid stimulates FA ethyl ester synthesis in HepG2 cells exposed to
      ethanol.
AB  - FA ethyl esters (FAEE) are nonoxidative metabolites of ethanol produced by the
      esterification of FA and ethanol. FAEE have been implicated as mediators of
      ethanol-induced organ damage in vivo and in vitro, and are markers of ethanol
      intake. Upon ethanol intake, FAEE are synthesized in the liver and pancreas in
      significant quantities. There is limited information on the stimulation of FAEE
      synthesis upon addition of exogenous FA in vitro. HepG2 cells were incubated with
      ethanol alone, ethanol with 25 microM linoleate, and ethanol with 25 microM
      stearate. The amount of FAEE in human hepatoblastoma (HepG2) cells was determined
      1-3 h after ethanol and FA addition. Stearate increased the FAEE concentration in
      HepG2 cells when incubated with the cells for 1 h, whereas linoleate did not
      increase the cellular FAEE concentration at any time. Ethyl palmitate, ethyl
      stearate, and ethyl oleate were the predominant FAEE species identified in all
      cases, independent of the specific supplemental FA added to the medium.

PMID- 14669971
TI  - Lack of stereospecificity in lysophosphatidic acid enantiomer-induced calcium
      mobilization in human erythroleukemia cells.
AB  - Lysophosphatidic acid (LPA) is a lipid mediator that, among several other
      cellular responses, can stimulate cells to mobilize calcium (Ca2+). LPA is known
      to activate at least three different subtypes of G protein-coupled receptors.
      These receptors can then stimulate different kinds of G proteins. In the present
      study, LPA and LPA analogs were synthesized from (R)- and (S)-glycidol and used
      to characterize the ability to stimulate Ca2+ mobilization. The cytosolic Ca2+
      concentration ([Ca2+]i) was measured in fura-2-acetoxymethylester-loaded human
      erythroleukemia (HEL) cells. Furthermore, a reverse transcriptase polymerase
      chain reaction was used to characterize LPA receptor subtypes expressed in HEL
      cells. The results show that HEL cells mainly express LPA1 and LPA2, although
      LPA3 might possibly be expressed as well. Moreover, LPA and its analogs
      concentration-dependently increased [Ca2+]i in HEL cells. The response involved
      both influx of extracellular Ca2+ and release of Ca2+ from intracellular stores.
      This is the first time the unnatural (S)-enantiomer of LPA, (S)-3-O-oleoyl-1-O
      phosphoryl-glycerol, has been synthesized and studied according to its ability to
      activate cells. The results indicate that this group of receptors does not
      discriminate between (R)- and (S)-enantiomers of LPA and its analogs. When
      comparing ether analogs having different hydrocarbon chain lengths, the
      tetradecyl analog (14 carbons) was found to be the most effective in increasing
      [Ca2+]i. Pertussis toxin treatment of the HEL cells resulted in an even more
      efficient Ca2+ mobilization stimulated by LPA and its analogs. Furthermore, at
      repeated incubation with the same ligand no further increase in [Ca2+]i was
      obtained. When combining LPA with the ether analogs no suppression of the new
      Ca2+ signal occurred. All these findings may be of significance in the process of
      searching for specific agonists and antagonists of the LPA receptor subtypes.

PMID- 14669972
TI  - Inhibitory action of emulsified sulfoquinovosyl acylglycerol on mammalian DNA
      polymerases.
AB  - We reported previously that sulfoquinovosyl diacylglycerol and sulfoquinovosyl
      monoacylglycerol (SQDG/SQMG) are potent inhibitors of mammalian DNA polymerases
      and DNA topoisomerase II, and can be potent immunosuppressive agents and
      anticancer chemotherapy agents [Matsumoto, Y., Sahara, H., Fujita T., Shimozawa,
      K., Takenouchi, M., Torigoe, T., Hanashima, S., Yamazaki, T., Takahashi, S.,
      Sugawara, F., et al., An Immunosuppressive Effect by Synthetic Sulfonolipids
      Deduced from Sulfonoquinovosyl Diacylglycerols of Sea Urchin, Transplantation 74,
      261-267 (2002); Sahara, H., Hanashima, S., Yamazaki, T., Takahashi, S., Sugawara,
      F., Ohtani, S., Ishikawa, M., Mizushina, Y., Ohta, K., Shimozawa, K., et al.,
      Anti-tumor Effect of Chemically Synthesized Sulfolipids Based on Sea Urchin's
      Natural Sulfonoquinovosylmonoacylglycerols, Jpn. J. Cancer Res. 93, 85-92
      (2002)]. In those experiments, the in vivo effectiveness greatly depended on the
      degree of water solubility of SQDG/SQMG. In the present work, we studied the
      emulsification of SQDG/SQMG in terms of their use in in vivo experiments. Lipid
      emulsions containing SQDG/SQMG (oil-in-water emulsions) in which the particle
      size was smaller than 100 nm were designed and synthesized, and then the
      biochemical modes of emulsified SQDG/SQMG were studied in comparison with those
      of SQDG/SQMG solubilized by DMSO. Emulsified SQDG/SQMG are also selective
      mammalian DNA polymerase inhibitors and potent antineoplastic agents but do not
      inhibit the DNA topoisomerase II activity. The growth inhibition effect of
      emulsified SQMG to NUGC-3 cancer cells was twofold stronger than DMSO-soluble
      SQMG (69 and 151 microM, respectively). From these results, the properties of
      lipid emulsions containing SQDG/SQMG and their possible use in in vivo
      experiments including clinical use are discussed.

PMID- 14669973
TI  - Lipid molarity affects liquid/liquid aroma partitioning and its dynamic release
      from oil/water emulsions.
AB  - Initial dynamic flavor release from oil/water emulsions containing different TAG
      phases was studied using a computerized apparatus and thermodesorption GC. A
      significant influence of lipid molarity on liquid/liquid partitioning and release
      of some flavor compounds was found. The release of the least hydrophobic
      compounds was not affected by any type of lipid. Hydrophobic compounds showed a
      positive correlation between their release and decreasing molarity of the lipid
      phase, that is, with increasing number of lipid molecules; only the most
      hydrophobic compounds did not show such a correlation. A strong linear
      correlation between low-melting TAG/water partition coefficients and lipid phase
      molarity was validated by volatile partition data of C6, C11, and C16
      alkane/water systems. Lipid phase transition from the liquid to solid state did
      not affect flavor partitioning and release. Neither experimental nor theoretical
      octanol/water partition coefficients agreed with experimental TAG/water and
      alkane/water partition coefficients.

PMID- 14669974
TI  - On the origin of cis-vaccenic acid photodegradation products in the marine
      environment.
AB  - The origin of 11-hydroxyoctadec-trans-12-enoic and 12-hydroxyoctadec-trans-10
      enoic acids (photodegradation products of cis-vaccenic acid) in the marine
      environment was investigated. cis-Vaccenic acid is commonly used as a bacterial
      biomarker; however, in heterotrophic bacteria the observed rates of cis-vaccenic
      acid photodegradation are negligible. Here, two hypotheses explaining the source
      of the photoproducts were tested. According to the first hypothesis, the
      photoproducts originate from aerobic anoxygenic bacteria, i.e.,
      photoheterotrophic organisms using bacteriochlorophyll-containing reaction
      centers. Alternatively, the photoproducts come from a heterotrophic bacterial
      community closely associated with senescent phytoplanktonic cells. cis-Vaccenic
      acid photodegradation was detected in both experimental setups. However, a
      detailed comparison of the cis-vaccenic acid photodegradation patterns with those
      observed in particulate matter samples of the DYFAMED station (Mediterranean Sea)
      suggests that photodegradation of heterotrophic bacteria attached to senescent
      phytoplanktonic cells constitutes the more likely source of cis-vaccenic acid
      oxidation products detected in situ.

PMID- 14669975
TI  - Fatty acids of lipid fractions in extracellular polymeric substances of activated
      sludge flocs.
AB  - Phospholipid (PL), glycolipid (GL), and neutral lipid (NL) FA, and the
      lipopolysaccharide 2- and 3-hydroxy (LPS 2-OH and 3-OH) FA of activated sludges
      and extracted extracellular polymeric substances (EPS) were determined on samples
      collected from two wastewater treatment plants. EPS extracted from sludges by
      means of sonication and cation exchange contained proteins (43.4%), humic-like
      substances (11.5%), nucleic acids (10.9%), carbohydrates (9.9%), and lipid-bound
      FA (1.8%). The lipids associated with EPS were composed of GL, PL, NL, and LPS
      acids in proportions of 61, 21, 16, and 2%, respectively. The profiles of lipid
      bound FA in activated sludges and EPS were similar (around 85 separate FA were
      identified). The FA signatures observed can be attributed to the likely presence
      of yeasts, fungi, sulfate-reducing bacteria, gram-positive and gram-negative
      bacteria, and, in lesser quantities, mycobacteria. Comparison of data from the
      dates of sampling (January and September) showed that there were more unsaturated
      PLFA in the EPS extracted from the activated sludges sampled in January. This
      observation could be partly related to microorganism adaptation to temperature
      variations. The comparison between two wastewater treatment plants showed that
      the FA profiles were similar, although differences in microbial community
      structure were also seen. Most of the FA in sludges had an even number of
      carbons.

PMID- 14669976
TI  - Digalactosyldiacylglycerol is a major glycolipid in floral organs of Petunia
      hybrida.
AB  - In higher plants, glycolipids such as monogalactosyldiacylglycerol (MGDG) and
      digalactosyldiacylglycerol (DGDG) are major components of chloroplast membranes
      in leaves. A recent study identified an isoform of MGDG synthase that is
      expressed specifically in floral organs, suggesting a novel function for
      glycolipids in flowers. To elucidate the localization and developmental changes
      of glycolipids and their biosynthetic activities in flowers, we carried out a
      series of analytical studies with Petunia hybrida. The results showed that the
      biosynthetic activities of galactolipid synthesis, particularly for DGDG,
      increased during flower development. Among the floral organs, the pistil had the
      highest galactolipid synthetic activity. Its specific activity for incorporation
      of UDP-galactose to yield galactolipids was estimated to be more than twice that
      of leaves, which are the major site of galactolipid synthesis in plant tissues.
      Analysis of lipid contents of pistils revealed that they contained higher amounts
      of galactolipids than other floral organs. Moreover, DGDG was more abundant than
      MGDG in both pistils and petals. These results show that DGDG is a major
      glycolipid in floral organs and that DGDG biosynthetic activity is highly
      upregulated in the pistils and petals of Petunia flowers.

PMID- 14669977
TI  - Which of the n-3 PUFA should be called essential?

PMID- 14669978
TI  - Mechanisms and biological consequences of nitrosative stress.

PMID- 14669979
TI  - Regulation of the expression of inducible nitric oxide synthase.
AB  - Nitric oxide (NO), generated by the inducible isoform of nitric oxide synthase
      (iNOS), has been described to have beneficial microbicidal, antiviral,
      antiparasital, immunomodulatory, and antitumoral effects. However, aberrant iNOS
      induction at the wrong place or at the wrong time has detrimental consequences
      and seems to be involved in the pathophysiology of several human diseases. iNOS
      is primarily regulated at the expression level by transcriptional and post
      transcriptional mechanisms. iNOS expression can be induced in many cell types
      with suitable agents such as bacterial lipopolysaccharides (LPS), cytokines, and
      other compounds. Pathways resulting in the induction of iNOS expression may vary
      in different cells or different species. Activation of the transcription factors
      NF-kappaB and STAT-1alpha, and thereby activation of the iNOS promoter, seems to
      be an essential step for iNOS induction in most cells. However, at least in the
      human system, also post-transcriptional mechanism are critically involved in the
      regulation of iNOS expression. The induction of iNOS can be inhibited by a wide
      variety of immunomodulatory compounds acting at the transcriptional levels and/or
      post-transcriptionally.

PMID- 14669980
TI  - Nitrosative stress and transcription.
AB  - Low NO concentrations synthesized by constitutively expressed NO synthases act on
      several signaling pathways activating transcription factors (TF), such as NF
      kappaB or AP-1, and thereby influence gene expression. In contrast, during
      inflammatory reactions the inducible NO synthase produces NO for prolonged
      periods of time. The resulting nitrosative stress directly affects redox
      sensitive TF like NF-kappaB, AP-1, Oct-1, c-Myb, or zinc finger-containing TF,
      but also additional mechanisms have been identified. Nitrosative stress in some
      cases induces expression of TF (AP-1, p53), indirectly modulates activity or
      stability of TF (HIF-1, p53) or their inhibitors (NF-kappaB), or modulates
      accessibility of promoters via increased DNA methylation or histone
      deacetylation. Depending on the promoter the result is induced, increased,
      decreased or even totally inhibited expression of various target genes. In
      unstimulated cells nitrosative stress increases NF-kappaB- or AP-1-dependent
      transcription, while in activated cells nitrosative stress rather abolishes NF
      kappaB- or AP-1-dependent transcription. Sometimes the oxygen concentration also
      is of prime importance, since under normoxic conditions nitrosative stress
      activates HIF-1-dependent transcription, while under hypoxic conditions
      nitrosative stress leads to inhibition of HIF-1-dependent transcription. This
      review summarizes what is known about effects of physiological NO levels as well
      as of nitrosative stress on transcription.

PMID- 14669981
TI  - Nitric oxide signalling with a special focus on lipid-derived mediators.
AB  - The ways in which cells communicate among each other concerns all aspects of
      biology, from developmental processes to diseases. Nitric oxide (NO) is one of
      the most remarkable and unusual regulatory molecules. It is a labile free radical
      gas that is not stored but generated on demand, and has been implicated in an
      extraordinarily diverse range of physiological and pathophysiological functions.
      The modulation of cell signalling by free radicals is an emerging area of
      research that provides insight into the orchestration of cell adaptation to a
      changing microenvironment. In a multicellular organism this serves to coordinate
      complex physiological responses, such as inflammation. Cell signalling is also
      accompanied by rapid remodelling of membrane lipids by activated lipases. The
      discovery that NO, which does not reversibly interact with membrane receptors
      like conventional hormones and growth factors, targets enzymes such as
      phospholipase A2, sphingomyelinases or ceramidases, has stimulated growing
      interest in the crosstalk between redox and lipid signalling.

PMID- 14669982
TI  - Potential of embryonic and adult stem cells in vitro.
AB  - Recent developments in the field of stem cell research indicate their enormous
      potential as a source of tissue for regenerative therapies. The success of such
      applications will depend on the precise properties and potentials of stem cells
      isolated either from embryonic, fetal or adult tissues. Embryonic stem cells
      established from the inner cell mass of early mouse embryos are characterized by
      nearly unlimited proliferation, and the capacity to differentiate into
      derivatives of essentially all lineages. The recent isolation and culture of
      human embryonic stem cell lines presents new opportunities for reconstructive
      medicine. However, important problems remain; first, the derivation of human
      embryonic stem cells from in vitro fertilized blastocysts creates ethical
      problems, and second, the current techniques for the directed differentiation
      into somatic cell populations yield impure products with tumorigenic potential.
      Recent studies have also suggested an unexpectedly wide developmental potential
      of adult tissue-specific stem cells. Here too, many questions remain concerning
      the nature and status of adult stem cells both in vivo and in vitro and their
      proliferation and differentiation/transdifferentiation capacity. This review
      focuses on those issues of embryonic and adult stem cell biology most relevant to
      their in vitro propagation and differentiation. Questions and problems related to
      the use of human embryonic and adult stem cells in tissue regeneration and
      transplantation are discussed.

PMID- 14669983
TI  - Ribosomal tolerance and peptide bond formation.
AB  - In the ribosome, the decoding and peptide bond formation sites are composed
      entirely of ribosomal RNA, thus confirming that the ribosome is a ribozyme.
      Precise alignment of the aminoacylated and peptidyl tRNA 3'-ends, which is the
      major enzymatic contribution of the ribosome, is dominated by remote interactions
      of the tRNA double helical acceptor stem with the distant rims of the peptidyl
      transferase center. An elaborate architecture and a sizable symmetry-related
      region within the otherwise asymmetric ribosome guide the A --> P passage of the
      tRNA 3'-end by a spiral rotatory motion, and ensures its outcome: stereochemistry
      suitable for peptide bond formation and geometry facilitating the entrance of
      newly formed proteins into their exit tunnel.

PMID- 14669984
TI  - Transcription of cathepsin B in glioma cells: regulation by an E-box adjacent to
      the transcription initiation site.
AB  - We have previously isolated the human cathepsin B promoter and shown that Sp1 and
      Ets factors are involved in the regulation of cathepsin B expression. Using
      mutagenesis, transient transfection and electrophoretic mobility shift assays
      (EMSAs), we further identified regulatory factors that mediate cathepsin B
      transcription in U87 human glioblastoma cells. An E-box element (CACGTG) adjacent
      to the transcription initiation site (at nucleotides -7 to -2) was found to be
      indispensable for cathepsin B promoter activity. Mutation of this E-box element
      in both pSCB2, a promoter construct with high promoter activity, and pSCB6, a
      construct with basal promoter activity, led to a 90% decrease in promoter
      activity in U87 cells. EMSAs demonstrated that upstream stimulatory factor 1 (USF
      1) and upstream stimulatory factor 2 (USF-2) bound to the E-box as a heterodimer.
      Chromatin immunoprecipitation assays revealed that both USF-1 and USF-2 were
      associated with the cathepsin B promoter. The roles of USF-1 and USF-2 in the
      regulation of cathepsin B expression were demonstrated by (i) co-transfection
      experiments showing that USF-1 or USF-2 increased promoter activity by 2.5-fold
      individually and by 3.4-fold together; (ii) co-transfection of pSCB6 with pUSF
      2deltaN (a dominant negative USF-2 expression plasmid) resulting in an 80%
      decrease in promoter activity; and (iii) mutation of the E-box element (from 5'
      CACGTG to 5'-CGCGTT in the pSCB6 basal promoter construct) abolishing
      transactivation of cathepsin B by USF-1 and USF-2. These results collectively
      indicate that an E-box at nucleotides -7 to -2 of the cathepsin B promoter is
      critical to the expression of cathepsin B and that binding of USF-1 and USF-2 to
      this E-box can regulate cathepsin B promoter activity.

PMID- 14669985
TI  - The catalytically active domain in the A subunit of calcineurin.
AB  - Calcineurin (CaN) is a heterodimer composed of a catalytic subunit A (CaNA) and a
      regulatory subunit B (CaNB). We report here an active truncated mutation of the
      rat CaNAdelta that contains only the catalytic domain (residues 1-347, also known
      as a/CaNA). The p-nitrophenyl phosphatase activity and protein phosphatase
      activity of a/CaNA were higher than that of CaNA. Both p-nitrophenyl phosphatase
      activity and protein phosphatase activity of a/CaNA were unaffected by CaM and
      the B-subunit; the B-subunit and CaM have relatively little effect on p
      nitrophenyl phosphatase activity and a crucial effect on protein phosphatase
      activity of CaNA. Mn2+ and Ni2+ ions effeciently activated CaNA. The Km of a/CaNA
      was about 16 mM, and the k(cat) of a/CaNA was 10.03 s(-1) using pNPP as
      substrate. With RII peptide as a substrate, the Km of a/CaNA was about 21 microM
      and the k(cat) of a/CaNA was 0.51 s(-1). The optimum reaction temperature was
      about 45 degrees C, and the optimum reaction pH was about 7.2. Our results
      indicate that a/CaNA is the catalytic core of CaNA, and CaN and the B-subunit
      binding domain itself might play roles in the negative regulation of the
      phosphatase activity of CaN. The results provide the basis for future studies on
      the catalytic domain of CaN.

PMID- 14669986
TI  - HIV TAT basic peptide is not a high-affinity ligand for VEGF receptor 2.
AB  - The 'transactivator of transcription' (TAT) protein of human immunodeficiency
      virus transforms cells in culture and promotes the development of tumors, so
      called Kaposi's sarcoma, in AIDS patients. TAT induces growth and differentiation
      of blood vessels and has been suggested to directly activate VEGF receptor 2
      expressed on endothelial cells through a peptide sequence located between amino
      acids 46 and 64, the so-called basic domain. This peptide mimics many aspects of
      TAT function when added to endothelial cells, even when expressed in the context
      of recombinant chimeric proteins. To define the exact sites of interaction
      between this peptide and VEGF receptor 2 we performed binding studies with
      recombinant proteins derived from the extracellular ligand binding domain of VEGF
      receptor 2. These in vitro binding studies showed that the TAT peptide binds with
      only low specificity to Ig-like domain 3 of the receptor, while VEGF interacts
      with receptor-derived proteins encompassing at least extracellular domains 1
      through 3. The original concept that the angiogenic properties of TAT basic
      peptide result from specific, high-affinity interaction with VEGF receptor 2 must
      therefore be revised. Apparently this peptide interacts with cells in multiple
      ways: by directly activating acidic cell surface-exposed receptors, by releasing
      extracellular matrix-bound growth factors such as bFGF and VEGF which then bind
      to their cognate receptors, and by activating intracellular signalling molecules
      with which basic peptide interacts upon translocation into cells.

PMID- 14669987
TI  - Immunogenicity and protectivity of Plasmodium falciparum EBA-175 peptide and its
      analog is associated with alpha-helical region shortening and displacement.
AB  - EBA-175 protein is used as a ligand in the binding of P. falciparum to red blood
      cells (RBCs). Evidence shows that the conserved peptide 1779 from this protein
      (with high red blood cell binding ability and known critical erythrocyte binding
      residues) plays an important role in the invasion process. This peptide is
      neither immunogenic nor protective; analogs having critical residues replaced by
      amino acids with similar volume or mass but different polarity were synthesized
      and inoculated into Aotus monkeys, and elicited different immunogenic and
      protective responses. Nuclear Magnetic Resonance (1H-NMR) studies revealed that
      peptide analog 21696 (non-immunogenic and non-protective) presents a large
      helical fragment, that the peptide 14012 (immunogenic and non-protective) helical
      fragment is smaller, while the peptide 22812 (immunogenic and protective) alpha
      helix is shorter in a different region and possesses greater flexibility at its N
      terminus. The presence of methionine residues could affect the structural
      stability of peptide 22812 and ultimately its immunological response. Our results
      suggest a new strategy for designing a new malaria multi-component subunit-based
      vaccine.

PMID- 14669988
TI  - Gene organization and molecular modeling of copper amine oxidase from Aspergillus
      niger: re-evaluation of the cofactor structure.
AB  - Amine oxidase AO-I from Aspergillus niger AKU 3302 has been reported to contain
      topa quinone (TPQ) as a cofactor; however, analysis of the p-nitrophenylhydrazine
      derivatized enzyme and purified active site peptides showed the presence of a
      carboxylate ester linkage of TPQ to a glutamate. The catalytic functionality of
      such a cross-linked cofactor has recently been shown unlikely by spectroscopic
      and voltammetric studies on synthesized model compounds. We have obtained
      resonance Raman spectra of native and substrate-reduced AO-I demonstrating that
      the catalytically active cofactor is unmodified TPQ. The primary structure of the
      enzyme (GenBank acc. no. U31869) has been reviewed and updated by repeated
      isolation and sequencing of AO-I cDNA. This allowed rectification of several
      errors that account for previously reported low homology to other amine oxidases
      in the regions around copper binding histididyl residues. The results were
      confirmed by cloning the ao-1 structural gene (GenBank acc. no. AF362473).
      Analysis of the gene 5'-upstream region of the gene revealed potential binding
      sites for an analog of NIT2, the nitrogen metabolism regulatory protein found in
      Neurospora crassa and other fungi. The molecular structure of AO-I was modeled by
      a comparative method using published crystal structures of amine oxidases as
      templates.

PMID- 14669989
TI  - Thermodynamic analysis of the dissociation of the aldolase tetramer substituted
      at one or both of the subunit interfaces.
AB  - The fructose-1,6-bis(phosphate) aldolase isologous tetramer tightly associates
      through two different subunit interfaces defined by its 222 symmetry. Both single
      and double-interfacial mutant aldolases have a destabilized quaternary
      structure, but there is little effect on the catalytic activity. These enzymes
      are however thermolabile. This study demonstrates the temperature-dependent
      dissociation of the mutant enzymes and determines the dissociation free energies
      of both mutant and native aldolase. Subunit dissociation is measured by
      sedimentation equilibrium in the analytical ultracentrifuge. At 25 degrees C the
      tetramer-dimer dissociation constants for each single-mutant enzyme are similar,
      about 10(-6) M. For the double-mutant enzyme, sedimentation velocity experiments
      on sucrose density gradients support a tetramer-monomer equilibrium. Furthermore,
      sedimentation equilibrium experiments determined a dissociation constant of 10(
      15) M3 for the double-mutant enzyme. By the same methods the upper limit for the
      dissociation constant of wild-type aldolase A is approximately 10(-28) M3, which
      indicates an extremely stable tetramer. The thermodynamic values describing
      monomer-tetramer and dimer-tetramer equilibria are analyzed with regard to
      possible cooperative interaction between the two subunit interfaces.

PMID- 14669990
TI  - Molecular recognition between Azotobacter vinelandii rhodanese and a sulfur
      acceptor protein.
AB  - The occurrence of rhodanese-like proteins in the major evolutionary phyla,
      together with the observed abundance of these proteins also within the same
      genome, suggests that their function cannot be limited to cyanide scavenging. The
      aim of the present study was to investigate whether Azotobacter vinelandii RhdA,
      an enzyme possessing unique biochemical and structural features with respect to
      other members of rhodanese homology superfamily, could recognize a suitable
      protein as a potential acceptor of the sulfane sulfur held on its catalytic Cys
      residue. Both the potential sulfur-delivery RhdA-S and the sulfur-deprived RhdA
      were found to interact with either holo- or apo-adrenodoxin, the 'substrate'
      protein used in this work. Interaction of RhdA-S with apo-adrenodoxin led to
      mobilization of RhdA-S sulfane sulfur. Under appropriate conditions, the sulfur
      released from RhdA-S was productively used for 2Fe-2S cluster reconstitution to
      yield holo-adrenodoxin from apo-adrenodoxin in the absence of any other sulfur
      source. A comparison of the reactivity of RhdA-S with protein and non-protein
      thiols allowed also some insights into the accessibility of the sulfane sulfur
      carried by RhdA.

PMID- 14669991
TI  - Cloning and characterization of a transmembrane-type serine protease from rat
      kidney, a new sodium channel activator.
AB  - We have cloned the gene of a new transmembrane-type serine protease from rat
      kidney, which activates sodium channels. The amino acid sequence deduced from a
      full-length cDNA revealed that transmembrane serine protease-1 (TMSP-1) is a
      member of the clan SA/family S1 of serine proteases, comprising a 30 amino acid
      prepropeptide, a mature form sequence of 274 amino acids starting with the Ile
      Val-Gly-Gly-Gln motif, and a common catalytic triad of serine proteases. The
      hydrophobic amino acid sequence in the carboxy-terminus of this enzyme suggests
      that it is a glycosylphosphatidylinositol-anchored protein. As revealed by
      quantitative reverse transcription-polymerase chain reaction analysis, it is
      highly expressed in kidney, small intestine, and stomach, and moderately
      expressed in lung, thymus, spleen and skin. The recombinant protease had an
      optimal pH at 9.0, selectively cleaved synthetic peptide substrates of trypsin,
      and was inhibited by aprotinin, leupeptin and benzamidine. Immunohistochemical
      studies revealed that this protease is predominantly expressed in cells from
      collecting ducts of the renal medulla. We also demonstrate that a C-terminally
      truncated variant of TMSP-1 significantly activates the epithelial sodium
      channel, and that its mRNA levels are upregulated by aldosterone. These
      observations suggest that it is a new member of the trypsin-type transmembrane
      proteases, which regulate sodium balance by activating the epithelial sodium
      channel.

PMID- 14669992
TI  - Aptamers that recognize the lipid moiety of the antibiotic moenomycin A.
AB  - Moenomycin A is an amphiphilic phosphoglycolipid antibiotic that interferes with
      the transglycosylation step in peptidoglycan biosynthesis. The antibiotic
      consists of a branched pentasaccharide moiety, connected to the moenocinol lipid
      via a glycerophosphate linker. We have previously described the selection of
      aptamers that require the lipid group and the disaccharide epitopes of the
      oligosaccharide moiety for moenomycin binding. Here we report that the enriched
      moenomycin-binding library contains sequences that evolved for specific
      recognition of the unpolar lipid group of the antibiotic. These results suggest
      that the evolution of hydrophobic binding pockets in RNA molecules may be much
      more common than previously assumed.

PMID- 14669993
TI  - Suboptimal action of NF-kappaB in Fanconi anemia cells results from low levels of
      thioredoxin.
AB  - Electrophoretic mobility shift assays (EMSA) revealed that under standard cell
      culture conditions NF-kappaB was induced in Fanconi anemia fibroblasts in
      contrast to control cells. Dithiothreitol, a potent synthetic redox potential
      delivering compound, when added to growing cells, prevented this induction of NF
      kappaB and, simultaneously, chromosomal instability was reduced. Fanconi anemia
      cells possess low endogenous levels of the naturally occurring antioxidant
      thioredoxin. Transfection of Fanconi anemia cells with thioredoxin cDNA
      containing a nuclear localization signal prevented both spontaneous as well as
      mitomycin C-induced chromosomal instability. A promotor construct with two NF
      kappaB binding sites in front of the CAT gene induced little CAT expression in
      cells with low thioredoxin content in spite of induced NF-kappaB. In cells with
      higher thioredoxin content CAT expression was increased. Cotransfection of the NF
      kappaB-dependent CAT plasmid with the Trx/nuc-plasmid into FA fibroblasts
      increased the CAT expression to almost that of control cells, indicating that in
      this model system with diminished thioredoxin content NF-kappaB requires
      thioredoxin for binding to its specific promotor. Since Fanconi anemia cells have
      low thioredoxin contents, NF-kappaB-dependent genes are expressed insufficiently.
      This explains part of the pathophysiological processes observed in Fanconi
      anemia.

PMID- 14669994
TI  - Modulation of the activation of extracellular signal-regulated kinase (ERK) and
      the production of inflammatory mediators by ADP-ribosylation inhibitors.
AB  - ADP-ribosylation is involved in nuclear factor kappaB (NF-kappaB)-dependent gene
      expression induced by lipopolysaccharide in murine macrophages. Here we have
      investigated the mechanism by which ADP-ribosylation inhibitors block signaling
      pathways induced in macrophages. In RAW264.7 macrophages the inducers of NF
      kappaB activate the production of reactive oxygen species and three mitogen
      activated protein kinases (MAPK), the extracellular signal regulated kinase
      (ERK), the c-jun N-terminal kinase/stress-activated protein kinase (JNK), and
      p38. We demonstrate that ADP-ribosylation inhibitors specifically inhibit ERK
      MAPK activation and reduce the release of inflammatory mediators such as tumor
      necrosis factor alpha (TNF-alpha), IL-6 and nitrite.

PMID- 14669995
TI  - Increase of anti-metastatic efficacy by selectivity- but not affinity
      optimization of synthetic serine protease inhibitors.
AB  - Although tumors frequently show elevated protease activities, the concept of anti
      proteolytic cancer therapy has lost momentum after failure of clinical trials
      with broad-spectrum matrix metalloproteinase inhibitors. Thus we need to adapt
      our design strategies for protease inhibitors. Here, we employed a series of
      seven structurally fine-modulated and pharmacokinetically closely related
      synthetic 4-amidinobenzylamine-based inhibitors with distinct selectivity for
      prototypical serine proteases in a murine T cell lymphoma liver metastasis model.
      This in vivo screening revealed efficacy of urokinase inhibitors but no
      correlation between urokinase selectivity or affinity and anti-metastatic effect.
      In contrast, factor Xa-selective inhibitors were more potent, demonstrating
      factor Xa or a factor Xa-like serine protease likely to be more determinant in
      this model. Factor Xa selectivity, but not affinity, significantly improved anti
      metastatic efficacy. For example, factor Xa inhibitors CJ-504 and CJ-510 exert
      similar affinity for factor Xa (K(i)=14 nM versus 8.8 nM) but CJ-504 was 70-fold
      more selective for factor Xa. This correlated with higher anti-metastatic
      efficacy (58.8% with CJ-504; 28.2% with CJ-510). Our results show that among the
      protease inhibitors employed that have affinities in the nanomolar range, the
      strategy of selectivity-optimization is superior to further improvement of
      affinity to significantly enhance anti-metastatic efficacy. This appreciation may
      be important for the future rational design of new anti-proteolytic agents for
      cancer therapy.

PMID- 14669996
TI  - Mast cell cathepsins C and S control levels of carboxypeptidase A and the
      chymase, mouse mast cell protease 5.
AB  - Carboxypeptidase A (CPA) is a metalloprotease, residing in the mast cell
      secretory granules together with chymases and tryptases. Little information is
      available with respect to the mechanisms that maintain or regulate the levels of
      stored proteases in the mast cell secretory granules. In this study we examined
      whether cathepsins C and S may be involved in the control of the levels of mast
      cell proteases. Mast cells cultured from bone marrow of cathepsin C- or S-null
      mice expressed higher levels of CPA protein and activity than cells from wild
      type mice. Similar increases in protein were observed for the mouse chymase, mast
      cell protease-5 (mMCP-5), but not for the tryptase, mMCP-6. Steady-state levels
      of CPA and mMCP-5 mRNA were similar in wild-type and cathepsin C-null mast cells,
      indicating that post-transcriptional mechanisms explain the observed cathepsin C
      dependence of CPA and mMCP-5 expression. The present study thus indicates novel
      roles for cathepsins C and S in regulating the levels of stored proteases in the
      mast cell secretory granules.

PMID- 14669997
TI  - Application of the C4'-alkylated deoxyribose primer system (CAPS) in allele
      specific real-time PCR for increased selectivity in discrimination of single
      nucleotide sequence variants.
AB  - This study describes a quantitative real-time PCR-based approach for
      discrimination of single nucleotide sequence variants, called CAPS (C4' alkylated
      primer system). To increase the discrimination potential of DNA polymerases
      against competing sequence variants of single nucleotides, 3'-terminally modified
      primers were designed carrying a methyl residue bound to the C4' of the
      thymidylate deoxyribose. In a model sequence system positional dependencies of
      modified thymidylate (at -1, -2, -3) were tested for their influence on
      discrimination. Highest discrimination factors were obtained with the
      modification at the ultimate 3'-position. In a comparison between Taq and Pwo DNA
      polymerases, substantial better results were obtained by Taq DNA polymerase. In
      contrast to conventional PCR methods for discrimination of sequence variants,
      achieving a maximum discrimination potential of about 20, CAPS is capable of
      obtaining sequence-specific amplifications of a desired target among
      discriminated templates with a dynamic range of 1:100. Therefore, CAPS is a
      method able to quantitatively discriminate two sequence variants only differing
      in a single base (e.g., SNP alleles or point mutations). The range of
      applications of this easy to perform, fast and reliable technique reaches from
      medical diagnostics, transplantation medicine, molecular and cell biology to
      human genetics. Targeting of SNPs assures a universal exertion of this method,
      since these markers are gender-independent, highly abundant and ubiquitous.

PMID- 14669998
TI  - Lipid peroxidation of lung surfactant due to reactive oxygen species released
      from phagocytes stimulated by bacteria from children with cystic fibrosis.
AB  - We used Pseudomonas aeruginosa, Burkholderia cepacia and Stenotrophomonas
      maltophilia, live or heat-killed, isolated from the airways of children with
      Cystic Fibrosis, to stimulate human neutrophils (PMN) and rat alveolar
      macrophages (AM) to produce reactive oxygen metabolites in the presence or
      absence of Curosurf, a natural porcine lung surfactant. We determined: (1) the
      amount of lipid peroxidation (LPO) as assessed by the amounts of malondialdehyde
      (MDA) and 4-hydroxyalkenals (4-HNE) using the LPO 586 test kit; (2) the
      production by AM of superoxide with the nitroblue tetrazolium test and (3) of
      nitric oxide (NO) with the Griess reaction. Stimulation of PMN or AM increases
      LPO of Curosurf and cell wall lipids. In both types of phagocytes, B. cepacia
      induced the highest LPO levels followed by P. aeruginosa and S. maltophilia. PMN,
      stimulated by live bacteria, induced higher LPO than those stimulated by heat
      killed bacteria. B. cepacia stimulated AM to produce more superoxide and NO than
      did P. aeruginosa and S. maltophilia. The high phagocyte-stimulating ability of
      B. cepacia and its higher surfactant LPO than those of the other bacteria used in
      this in vitro study may play a role in vivo in the serious clinical condition
      known as the "Cepacia syndrome".

PMID- 14669999
TI  - N-acetylcysteine protects mice from lethal endotoxemia by regulating the redox
      state of immune cells.
AB  - The excessive production of reactive oxygen species (ROS) associated with
      inflammation leads to oxidative stress, which is involved with the high mortality
      from several diseases such as endotoxic shock and can be controlled to a certain
      degree by antioxidants. The immune cells use ROS in order to support their
      functions and, therefore, need adequate levels of antioxidant defenses in order
      to avoid the harmful effect of an excessive ROS production. In the present work,
      the effect of the administration of the antioxidant N-acetylcysteine (NAC) on the
      redox state of peritoneal macrophages and lymphocytes from mice with lethal
      endotoxic shock (100 mg/kg i.p. of lipopolysaccharide, LPS), was studied. In both
      types of immune cells at 0, 2, 4, 12 and 24 h after LPS injection, an increase of
      ROS, of the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha), the
      lipid peroxidation (malonaldehyde levels, MDA), inducible nitric oxide synthase
      (iNOS) expression and the oxidized/reduced glutathione (GSSG/GSH) ratio, as well
      as a decrease of enzymatic antioxidant defenses, such as superoxide dismutase
      (SOD) and catalase (CAT) activity, was observed. The injection of NAC (150 mg/kg
      i.p. at 30 min after LPS injection) decreased the ROS, the TNFalpha the MDA
      levels, iNOS expression and the GSSG/GSH ratio, and increased the antioxidant
      defenses in both macrophages and lymphocytes. Moreover, the NAC treatment
      prevented the activation of nuclear translocation of the nuclear factor kappaB
      (NF-kappaB), which regulates ROS, inflammatory cytokines and antioxidant levels.
      Our present results provide evidence that both cell types have a relevant role in
      the pathogenesis of endotoxic shock, and that NAC, by improving the redox state
      of these immune cells, could increase mouse survival. Thus, antioxidants could
      offer an alternative treatment of human endotoxic shock.

PMID- 14670000
TI  - Differential response of lymphocytes and neutrophils to high intensity physical
      activity and to vitamin C diet supplementation.
AB  - We have determined the effects of chronic vitamin C intake on neutrophil and
      lymphocyte antioxidant defences during the acute phase immune response induced by
      intense exercise. Blood samples were taken from 16 voluntary athletes in basal
      conditions, both immediately after and 1 h after a duathlon competition.
      Sportsmen's nutrient intakes were determined before the competition. After
      determining the basal plasmatic ascorbate levels, the results were analysed
      taking into account the vitamin C intake and their plasmatic levels. Two groups
      were constituted, the vitamin C supplemented group and the control group, with
      the dietary vitamin C intake as the only statistical difference between groups.
      The duathlon competition induced a significant neutrophilia, which was higher in
      the supplemented group. Lymphocyte antioxidant enzyme activities increased after
      the competition, with a higher increase in SOD activity in the control group than
      in the supplemented one. The competition decreased neutrophil antioxidant enzyme
      activities and neutrophil ascorbate concentration. The decrease in the SOD
      activity in the supplemented group was higher than in the control group. Finally,
      the duathlon competition increased the expression of MAC-1 neutrophil adhesion
      molecule in the supplemented group. High vitamin C intake influenced the response
      of neutrophils and lymphocytes to oxidative stress induced by exercise,
      increasing the neutrophil activation.

PMID- 14670001
TI  - Identification of the several new radicals formed in the reaction mixture of
      oxidized linoleic acid with ferrous ions using HPLC-ESR and HPLC-ESR-MS.
AB  - ESR, HPLC-ESR and HPLC-ESR-MS analyses were performed for the reaction mixtures
      of oxidized linoleic acid with ferrous ions combined use of spin trapping
      technique. More than 14 peaks were detected on the HPLC-ESR elution profile. In
      addition to 7-carboxyheptyl and pentyl radicals, several new radicals such as 7
      carboxyldihydroxyheptyl, 1,5-dihydroxypentyl, 8-carboxy-1-hydroxyoctyl, 7-carboxy
      1-hydroxyheptyl, 1-hydroxypentyl and 1-hydroxyhexyl were identified using HPLC
      ESR and HPLC-ESR-MS.

PMID- 14670002
TI  - Effect of increased intake of dietary animal fat and fat energy on oxidative
      damage, mutation frequency, DNA adduct level and DNA repair in rat colon and
      liver.
AB  - The effect of high dietary intake of animal fat and an increased fat energy
      intake on colon and liver genotoxicity and on markers of oxidative damage and
      antioxidative defence in colon, liver and plasma was investigated in Big Blue
      rats. The rats were fed ad libitum with semi-synthetic feed supplemented with 0,
      3, 10 or 30% w/w lard. After 3 weeks, the mutation frequency, DNA repair gene
      expression, DNA damage and oxidative markers were determined in liver, colon and
      plasma. The mutation frequency of the lambda gene cII did not increase with
      increased fat or energy intake in colon or liver. The DNA-adduct level measured
      by 32P-postlabelling decreased in both liver and colon with increased fat intake.
      In liver, this was accompanied by a 2-fold increase of the mRNA level of
      nucleotide excision repair (NER) gene ERCC1. In colon, a non-statistically
      significant increase in the ERCC1 mRNA levels was observed. Intake of lard fat
      resulted in increased ascorbate synthesis and affected markers of oxidative
      damage to proteins in liver cytosol, but not in plasma. The effect was observed
      at all lard doses and was not dose-dependent. However, no evidence of increased
      oxidative DNA damage was found in liver, colon, or urine. Thus, lard intake at
      the expense of other nutrients and a large increase in the fat energy consumption
      affects the redox state locally in the liver cytosol, but does not induce DNA
      damage, systemic oxidative stress or a dose-dependent increase in mutation
      frequency in rat colon or liver.

PMID- 14670003
TI  - X-ray-induced oxidative stress: DNA damage and gene expression of HO-1, ERCC1 and
      OGG1 in mouse lung.
AB  - Effects of X-ray induced oxidative stress in mouse lungs were studied in terms of
      DNA damage and expression of antioxidant defense and DNA repair genes. Lung
      samples were collected immediately after, and 3, 6, and 22 h after irradiation
      with 1, 3, 10 or 30 Gy X-rays of the thorax. The levels of strand breaks (SB),
      formamidopyrimidine DNA glycosylase (FPG) and endonuclease III (ENDOIII)
      sensitive sites, detected by the comet assay, were increased dose-dependently
      immediately after irradiation, whereas 8-oxo-7,8-dihydro-2'-deoxyguanosine
      analyzed by HPLC-EC was unaltered, possibly due to a relatively high background
      level (2.5/10(6) dG in control tissue). Complete repair of SB was observed 3 h
      after irradiation, whereas the period required for repair of ENDOIII and FPG
      sensitive sites was longer. Determined by RT-PCR, the mRNA expression of heme
      oxygenase-1 (HO-1) was increased 40-fold 6 h after irradiation, whereas the
      expression of 8-oxoguanine glycosylase (OGG1) and ERCC1 were increased 2.5-fold 6
      h after exposure, with saturation at the lowest dose. In conclusion, this study
      shows the feasibility of partial-body X-ray irradiation as an in vivo model for
      induction and repair of oxidative DNA damage, and expression of relevant DNA
      repair and antioxidant defense genes.

PMID- 14670004
TI  - Inhibition of NF-kB renders cells more vulnerable to apoptosis induced by amyloid
      beta peptides.
AB  - One of the mechanisms leading to neurodegeneration during Alzheimer's disease
      (AD) is amyloid beta peptide neurotoxicity. In response to a variety of stress
      insults, namely oxidative stress, the transcription factor NF-kB can be
      activated. We have previously shown that amyloid beta peptides 25-35 and 1-40 (A
      beta 25-35 and A beta 1-40) induces cell death. In response to A beta 25-35 or 1
      40 treatment, we observed an increase in superoxide dismutase (SOD) activity in
      NT2 cells. Amyloid beta peptides also induced an increase in SOD expression
      levels. This could result from NF-kB activation, as determined by the expression
      of p65. We observed that the NF-kB inhibitor, PDTC, prevented SOD overexpression
      after A beta treatment. Previously we have shown that A beta peptides could
      activate caspases-mediated apoptotic cell death. In this study, we analyzed if NF
      kB activation prevented cells from caspases-activation and we also observed that
      inhibition of NF-kB by PDTC induced an increase in caspase-3 and caspase-6
      activation. Taken together, these data suggest that pharmacological induction of
      NF-kB can be a potential target in Alzheimer's disease treatment.

PMID- 14670005
TI  - Inverse response of leukocyte heat shock proteins and DNA damage to exercise and
      heat.
AB  - Elevated ambient temperature may exert an additional impact on the exercise
      induced expression of heat shock proteins (HSP) and DNA damage in leukocytes. The
      protective functions of HSP include antioxidative and antiapoptotic effects and
      may prevent damage to DNA. Twelve athletes completed a continuous run (75%
      VO2max) on the treadmill, six at 28 degrees C and six at 18 degrees C room
      temperature. Leukocyte expression of HSP27 and inducible HSP70 was analyzed on
      mRNA- (RT-PCR) and protein-level (flow cytometry), while DNA damage was
      quantified by the comet assay. High ambient temperature induced an additional
      accumulation of HSP-mRNA and -protein in leukocytes compared with the exercise
      induced expression at 18 degrees C. HSP27 showed a special heat sensitivity.
      Surprisingly, the increase of DNA damage was less pronounced after exercise at 28
      degrees C compared to 18 degrees C although heat shock in vitro clearly induced
      DNA damage. The inverse relation between HSP and DNA damage may indicate
      functions of HSP which protect against exercise-induced DNA-damage in terms of
      thermotolerance or apoptosis.

PMID- 14670006
TI  - Protein hydroperoxides are a major product of low density lipoprotein oxidation
      during copper, peroxyl radical and macrophage-mediated oxidation.
AB  - Damage to apoB100 on low density lipoprotein (LDL) has usually been described in
      terms of lipid aldehyde derivatisation or fragmentation. Using a modified FOX
      assay, protein hydroperoxides were found to form at relatively high
      concentrations on apoB100 during copper, 2,2'-azobis(amidinopropane)
      dihydrochloride (AAPH) generated peroxyl radical and cell-mediated LDL oxidation.
      Protein hydroperoxide formation was tightly coupled to lipid oxidation during
      both copper and AAPH-mediated oxidation. The protein hydroperoxide formation was
      inhibited by lipid soluble alpha-tocopherol and the water soluble antioxidant,
      7,8-dihydroneopterin. Kinetic analysis of the inhibition strongly suggests
      protein hydroperoxides are formed by a lipid-derived radical generated in the
      lipid phase of the LDL particle during both copper and AAPH mediated oxidation.
      Macrophage-like THP-1 cells were found to generate significant protein
      hydroperoxides during cell-mediated LDL oxidation, suggesting protein
      hydroperoxides may form in vivo within atherosclerotic plaques. In contrast to
      protein hydroperoxide formation, the oxidation of tyrosine to protein bound 3,4
      dihydroxyphenylalanine (PB-DOPA) or dityrosine was found to be a relatively minor
      reaction. Dityrosine formation was only observed on LDL in the presence of both
      copper and hydrogen peroxide. The PB-DOPA formation appeared to be independent of
      lipid peroxidation during copper oxidation but tightly associated during AAPH
      mediated LDL oxidation.

PMID- 14670007
TI  - ESR spin trapping studies of free radicals generated from nitrofuran derivative
      analogues of nifurtimox by electrochemical and Trypanosoma cruzi reduction.
AB  - Electron spin resonance (ESR) spectra of radicals obtained from two analogues of
      the antiprotozoal drug nifurtimox by electrolytic and Trypanosoma cruzi reduction
      were analyzed. The electrochemistry of these compounds was studied using cyclic
      voltammetry. STO 3-21G ab initio and INDO molecular orbital calculations were
      performed to obtain the optimized geometries and spin distribution, respectively.
      The antioxidant effect of glutathione on the nitroheterocycle radical was
      evaluated. DMPO spin trapping was used to investigate the possible formation of
      free radicals in the trypanosome microsomal system. Nitro1 and Nitro2 nitrofuran
      analogues showed better antiparasitic activity than nifurtimox. Nitro2 produced
      oxygen redox cycling in T. cruzi epimastigotes. The ESR signal intensities were
      consistent with the trapping of either the hydroxyl radical or the Nitro2
      analogue radicals. These results are in agreement with the biological observation
      that Nitro2 showed anti-Chagas activity by an oxidative stress mechanism.

PMID- 14670008
TI  - Semichronic inhibition of glutathione reductase promotes oxidative damage to
      proteins and induces both transcription and translation of tyrosine hydroxylase
      in the nigrostriatal system.
AB  - We have evaluated the effect of N,N-bis (2-chloroethyl)-N-nitrosourea (BCNU), an
      inhibitor of glutathione reductase (GR), on the oxidative status along with the
      integrity of the nigrostriatal dopaminergic system of the rat. The oxidative
      status was studied by the quantification of carbonyl groups coupled to protein
      homogenates. Moreover, the specific oxidations in glial fibrillary acidic protein
      (GFAP) and neurofilament-200 (NF-200) were also measured. The results show that
      oxidative damage in proteins in the nigrostriatal system is confined to the
      striatum. Specific carbonyl groups coupled to native NF-200 and GFAP were also
      increased. These changes were accompanied by reactive astrocytosis in striatum
      but not in substantia nigra. In substantia nigra, decreased levels of dopamine
      (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were observed following BCNU
      treatment. In contrast, DA levels were increased in the striatum along with an
      overall decrease in the ratios of DA metabolites to DA. We also studied the mRNA
      levels for tyrosine hydroxylase (TH) and the dopamine transporter (DAT) by in
      situ hybridization. TH mRNA but not DAT mRNA was significantly induced in
      substantia nigra following BCNU treatment, which was consistent with significant
      elevations in TH enzyme amount and activity and unchanged DA uptake in striatum.
      All these results support the DA free radical hypothesis and the key role of the
      striatal glutathione system in protecting the striatal system against oxidative
      stress.

PMID- 14670009
TI  - Antioxidant activity of oligomeric acylphloroglucinols from Myrtus communis L.
AB  - The use of myrtle (Myrtus communis L.) as a culinary spice and as a flavoring
      agent for alcoholic beverages is widespread in the Mediterranean area, and
      especially in Sardinia. Myrtle contains unique oligomeric non-prenylated
      acylphloroglucinols, whose antioxidant activity was investigated in various
      systems. Both semimyrtucommulone (1) and myrtucommulone A (2) showed powerful
      antioxidant properties, protecting linoleic acid against free radical attack in
      simple in vitro systems, inhibiting its autoxidation and its FeCl3- and EDTA
      mediated oxidation. While both compounds lacked pro-oxidant activity,
      semimyrtucommulone was more powerful than myrtucommulone A, and was further
      evaluated in rat liver homogenates for activity against lipid peroxidation
      induced by ferric-nitrilotriacetate, and in cell cultures for cytotoxicity and
      the inhibition of TBH- or FeCl3-induced oxidation. The results of these studies
      established semimyrtucommulone as a novel dietary antioxidant lead.

PMID- 14670010
TI  - Red-wine beneficial long-term effect on lipids but not on antioxidant
      characteristics in plasma in a study comparing three types of wine--description
      of two O-methylated derivatives of gallic acid in humans.
AB  - The purpose of this double clinical study was (1) to evaluate the effect of one
      single intake (300 ml) of red wine (RW) on the plasma antioxidant capacity (pAOC)
      and plasma phenolics over the 24-h time period following the intake, and (2) to
      compare the long-term effects of daily intakes (250 ml/d) of RW, white wine (WW)
      and Champagne (CH) on the plasma and LDL characteristics of healthy subjects. In
      the first part, blood samples were collected just before and after wine
      consumption. In the second part, subjects received the 3 types of wine
      successively, only at the mealtime, over 3-week periods separated by a 3-week
      wash out. Blood samples were drawn in fasting condition before and after each 3
      week wine consumption period. The peak of pAOC was at 3-4 h following the single
      intake of RW, that of catechin was at 4 h (0.13 micromol/l) and that of gallic
      acid and caffeic acid was earlier (< or = 1.5 and 0.3 micromol/l, respectively).
      In plasma, the major form of gallic acid was 4-O-methylated, but a minor form
      (the 3-O-methyl derivative) appeared. In the long term study, no wine was able to
      change LDL oxidizability, but some other parameters were modified specifically:
      RW decreased pAOC (without changing TBARS and uric acid plasma levels), LDL
      lipids and total cholesterol (TC), and increased plasma apoA1, whereas CH
      increased plasma vitamin A. The beneficial effect of RW seems to mainly be
      explained by its action on lipid and lipoprotein constants, and not by its
      antioxidant one.

PMID- 14670011
TI  - Alpha-tocopherol content and alpha-tocopherol transfer protein expression in
      leukocytes of children with acute leukemia.
AB  - Alpha-tocopherol (a form of vitamin E) is a fat-soluble vitamin that can prevent
      lipid peroxidation of cell membranes. This antioxidant activity of alpha
      tocopherol can help to prevent cardiovascular disease, atherosclerosis and
      cancer. We investigated the alpha-tocopherol level and the expression of alpha
      tocopherol transfer protein (alpha-TTP) in the leukocytes of children with
      leukemia. The plasma and erythrocyte alpha-tocopherol levels did not differ
      between children with leukemia and the control group. However, lymphocytes from
      children with leukemia had significantly lower alpha-tocopherol levels than
      lymphocytes from the controls (58.4 +/- 39.0 ng/mg protein versus 188.9 +/-
      133.6, respectively; p < 0.05), despite the higher plasma alpha
      tocopherol/cholesterol ratio in the leukemia group (5.83 +/- 1.64 micromol/mmol
      versus 4.34 +/- 0.96, respectively; p < 0.05). No significant differences in the
      plasma and leukocyte levels of isoprostanes (the oxidative metabolites of
      arachidonic acid) were seen between the leukemia patients and controls. The
      plasma level of acrolein, a marker of oxidative stress, was also similar in the
      two groups. Investigation of alpha-TTP expression by leukocytes using real-time
      PCR showed no difference between the two groups. These findings suggest that
      there may be comparable levels of lipid peroxidation in children with untreated
      leukemia and controls, despite the reduced alpha-tocopherol level in leukemic
      leukocytes.

PMID- 14670012
TI  - Conventional abdominal aortic aneurysm repair: evidence-based assessment.

PMID- 14670013
TI  - Primary tumors of the thoracoabdominal aorta: surgical treatment of 5 patients
      and review of the literature.
AB  - The objectives of this study were to describe five cases involving primary tumors
      of the thoracoabdominal aorta and to review the pertinent literature. Between
      April 1990 and April 2000, we performed surgery on five patients with primary
      tumors of the aorta (PTA). There were three men and two women ranging in age from
      37 to 65 years (mean, 49.8 years). The presenting manifestations were
      renovascular hypertension in four cases, including three associated with
      abdominal angina and lower extremity embolism in one case. In all patients
      aortograms identified atherosclerotic-like occlusive lesions in the
      thoracoabdominal aorta extending to the descending thoracic aorta in three cases,
      visceral arteries in four cases, and infrarenal aorta in one case. Preoperative
      histological diagnosis of PTA was achieved in two patients following open repair
      with placement of an aortoaortic graft in one case and peripheral embolectomy in
      one case. In two cases, diagnosis of PTA was strongly suspected before or during
      the procedure. In the remaining case, diagnosis was not achieved until the
      definitive histological report. In two patients surgical treatment was carried
      out with curative intent (aortic resection with graft replacement). In two cases
      surgical treatment was incomplete (endarterectomy of the aorta and visceral
      arteries). In the remaining case surgical treatment was purely palliative (aortic
      and superior mesenteric artery bypass). Histological findings demonstrated
      intimal-type sarcoma in two cases, leiomyosarcoma in one case, and angiosarcoma
      in one case. In the remaining case, histological analysis was unfeasible for
      technical reasons. One patient died due to massive cerebral embolism 2 days after
      surgical treatment involving revascularization of the aortic arch carried out
      with hypothermic circulatory arrest. One patient developed secondary paraplegia.
      All four patients who survived the immediate postoperative period died of tumor
      related complications and cachexia at 5, 7, 16, and 24 months after the initial
      surgical procedure. The results of this small series as well as those of 130
      previously reported cases confirm the extremely dismal prognosis of PTA. Mean
      overall survival for patients presenting PTA was less than 16 months. Survival at
      5 years was 8%. Survival rates appear to be higher after surgical treatment and
      were significantly improved by adjuvant chemotherapy. The main factors correlated
      with poor prognosis were intimal type, involvement of the ascending aorta, aortic
      arch, or visceral aorta, and incomplete resection.

PMID- 14670014
TI  - Endovascular treatment of anastomotic false aneurysms of the abdominal aorta.
AB  - Conventional surgical treatment of anastomotic false abdominal aortic aneurysms
      (AFAA) is technically difficult. Morbidity-mortality rates are higher than those
      for surgery of infrarenal abdominal aortic aneurysm (AAA). Endovascular
      management without laparotomy or aortic clamping represents an attractive
      alternative. The purpose of this study was to determine the immediate and middle
      term outcome of endovascular management of AFAA. Between 1998 and 2001, 10
      patients were treated for AFAA by placement of an endograft. The initial
      procedure was aortobifemoral bypass for occlusive artery disease in eight cases
      and resection and grafting for AAA in two cases. Mean age was 70 years. Seven
      patients were classified ASA 3 or 4. Three patients presented cardiac
      insufficiency with left ventricular ejection fraction <40%. Eight patients were
      treated using an aortounilateral iliac artery endograft in association with
      crossover femorofemoral bypass (3 AneuRx, 2 Endologix, 1 Talent, 1 Zenith, 1
      surgeon-made stent). Two patients were treated with an aortoaortic endograft (1
      Talent, 1 surgeon-made stent). In two patients extraperitoneal exposure of the
      common iliac artery was required for introduction of the stent in one case and
      for surgical closure of the iliac artery in the other case. A total of nine
      patients underwent another surgical procedure in association with stenting. Four
      endografts were custom-made. Endograft deployment was successful in all cases. No
      patient died during the postoperative period. Postoperative computed tomography
      (CT) scan confirmed exclusion of the aneurysmal sac in all cases. The mean
      duration of hospitalization was 13 days (range, 5-28 days). During follow-up
      (mean duration, 17.7 months; range, 5-42 months), one patient died from heart
      related causes. No direct or indirect endoleak was detected by CT scan follow-up
      and a significant reduction in AFAA diameter was noted in the eight patients with
      follow-up periods lasting 6 months or more. One patient developed occlusion of an
      aortounilateral iliac artery endograft and was treated by axillobifemoral bypass.
      In one patient stenosis of the distal end of an aortounilateral iliac endograft
      was discovered by duplex scan and successfully treated by dilatation.
      Endovascular treatment of AFAA is technically feasible but requires more complex
      procedures involving associated surgical procedures and use of custom-made
      endografts. The morbidity-mortality rate in this small series of high-risk
      patients was low. Immediate and middleterm exclusion of AFAA was good.

PMID- 14670015
TI  - Endovascular treatment of isolated atherosclerotic stenosis of the infrarenal
      abdominal aorta: long-term outcome.
AB  - The purpose of this multicenter study was to assess the long-term outcome of
      endovascular treatment of isolated atherosclerotic stenosis of the infrarenal
      abdominal aorta on the basis of clinical and ultrasound examination. Clinical,
      ultrasound, and angiographic findings from 36 women and 50 men (mean age, 53.2
      years) treated for atherosclerotic stenosis of the infrarenal abdominal aorta
      were reviewed. Patients had claudication in 74 cases and rest pain in 4. Seven
      patients presented trophic manifestations and one had blue toe syndrome. Mean
      preoperative systolic index was 0.71. Mean diameter reduction was 77%.
      Circumferential calcification was partial in 36 cases (41%) and complete in 30
      cases (35%). Percutaneous transluminal angioplasty was performed using the single
      balloon technique in 60 cases and double-balloon technique in 26 cases. A stent
      was placed in 76 cases (88%) by necessity in 34% of cases (22 residual stenoses,
      4 dissections). Completion angiographic findings were considered good in 82 cases
      (95%). The remaining four patients had residual stenosis with a diameter
      reduction >30%. One patient died during the immediate postoperative period from
      septicemia unrelated to treatment (early mortality, 1.2%). Aortic angioplasty was
      complicated by stent detachment from the angioplasty balloon in two patients,
      retroperitoneal hematoma in one, peripheral embolism in two, puncture-site
      hematoma in three, myocardial infarction in one, and thrombophlebitis of deep
      femoral artery in one patient (early morbidity, 9.3%). All patients underwent
      follow-up with clinical and hemodynamic evaluation (mean follow-up, 31 months).
      Actuarial survival at 3 years was 91%. Primary actuarial patency was 94% at 1
      year, 89% at 3 years, and 77% at 5 years. Aortic restenosis occurred in seven
      patients and was treated by angioplasty in two, aortobifemoral bypass in four,
      and surveillance in one. Mean systolic index was 0.89. Statistical analysis of
      patency demonstrated no factor predictive of long-term complication. From the
      long-term follow-up findings in this study, we conclude that aortic angioplasty
      is a reliable minimally invasive technique for treatment of isolated
      atherosclerotic stenosis of the infrarenal abdominal aorta.

PMID- 14670016
TI  - Modalities of surveillance after carotid endarterectomy: impact of surgical
      technique.
AB  - The purpose of this study was to assess the need for follow-up duplex scan (DS) 1
      year after carotid endarterectomy (CE) performed with prosthetic patching and
      intraoperative completion arteriography. Between April 1994 and December 2000, a
      total of 605 CE procedures with prosthetic patch closure and intraoperative
      completion arteriography were performed in 540 patients. All patients underwent
      DS at 4 days and then yearly after the procedure. Five patients died during the
      early postoperative course and eight suffered a nonfatal stroke (combined
      neurological morbidity-mortality rate, 2.4%). Intraoperative completion
      arteriography showed abnormalities in 114 cases, including 17 involving the
      internal carotid artery (ICA) and 73 involving the external carotid artery (ECA).
      Successful revision was achieved in all cases and confirmed by repeat
      arteriography. Postoperative DS at 4 days detected three abnormalities involving
      the ICA (0.5%), including asymptomatic occlusion in one case and residual
      stenosis >50% in two cases. Ninety-eight percent of patients were stenosis-free
      at 1 year. Actuarial stroke-free survival was 98.3% at 3 years. Diameter
      reduction of the contralateral carotid artery progressed over 70% within 1 year
      after CE in 22.9% of patients with contralateral carotid stenosis over 50% at the
      time of the initial intervention. The findings of this study indicate that DS
      follow-up 1 year after CE with intraoperative completion arteriography is
      unnecessary unless postoperative DS demonstrates residual stenosis of the ICA.
      However, DS at 1 year is beneficial for patients presenting with contralateral
      carotid artery disease with diameter reduction >50% at the time of CE.

PMID- 14670017
TI  - Surgical treatment of recurrent carotid artery stenosis and carotid artery
      stenosis after neck irradiation: evaluation of operative risk.
AB  - Surgical treatment of recurrent carotid artery stenosis after endarterectomy and
      carotid artery stenosis after neck irradiation purportedly has a higher
      complication rate than primary carotid endarterectomy (CEA). Accordingly, carotid
      angioplasty has been proposed as a safer alternative. The purpose of this study
      was to evaluate operative risks on the basis of our experience with these
      lesions. A series of 679 carotid revascularizations (CRV) performed over a period
      of 9 years was retrospectively reviewed. Immediate outcome and operative
      technique was analyzed in three groups: group 1 included 549 "routine" CRV, group
      2 included 8 CRV for recurrent stenosis after CEA, and group 3 consisted of 11
      CRV for stenosis after neck irradiation. No difference in revascularization
      techniques was found between groups 1 and 2. In contrast there were fewer CEA and
      resection-anastomosis procedures in group 2 than in group 1 (62.5% vs. 98.2%; p <
      0.0006) and more bypass procedures (37.5% vs. 1.8%; p = 0.0015). The cumulative
      neurological morbidity/mortality rate (CMMR) was 0% in groups 2 and 3 as compared
      to 4.4% in group 1. In comparison with group 1, early and permanent neurological
      morbidity rates were significantly higher in both group 2 (2.2% vs. 25.0%; p =
      0.015 and 0.2% vs. 12.5%; p = 0.028, respectively) and group 3 (2.2% vs. 18.2%; p
      = 0.028 and 0.2% vs. 9.1%; p = 0.039, respectively). Surgical treatment of
      recurrent stenosis after CEA and stenosis after neck irradiation is not
      associated with a higher CMMR. The only potentially valid justification for using
      percutaneous transluminal angioplasty in these patients would be a higher risk of
      cervical neurological morbidity.

PMID- 14670018
TI  - Long-term outcome of femoral above-knee popliteal artery bypass using autologous
      saphenous vein versus expanded polytetrafluoroethylene grafts.
AB  - Despite a recent flurry of publications on preferred techniques for femoral above
      knee popliteal artery bypass, controversy persists over the use of autologous
      saphenous vein and expanded polytetrafluoroethylene (ePTFE) grafts. The purpose
      of this study was to compare our long-term results using these two bypass
      materials. In a series of 474 infrainguinal bypasses performed between January
      1993 and December 1998, we performed a total of 75 femoral above-knee popliteal
      artery bypass using an autologous saphenous vein graft in 48 cases (64%) and an
      ePTFE graft in 27 cases (36%). Prosthetic grafts were used by choice in 17 cases
      and by necessity due to the absence of useable vein in 10 cases. There were 55
      men and 18 women with a mean age of 70 years. The indication for bypass was lower
      extremity arterial occlusive disease at stage II in 17 cases (22.7%), stage III
      in 9 cases (12%), and stage IV in 36 cases (48%); subacute ischemia in 8 cases
      (10.7%); and femoropopliteal aneurysm in 5 cases (6.7%). Preoperative
      arteriography demonstrated three patent leg arteries in 15.5% of cases, two
      patent leg arteries in 43.5%, and one patent leg artery in 41%. There was no
      significance difference between the vein graft and ePTFE graft groups with regard
      to indications and arteriographic findings. No patient died during the immediate
      postoperative period. The mean duration of follow-up was 25.5 months (range, 3 to
      108 months). The primary patency rate at 4 years was 82.2 +/- 8% for venous
      bypass vs. 80.6 +/- 11.8% for ePTFE bypass (p = 0.42). The secondary patency rate
      at 4 years was 84.7 +/- 7.4% for vein bypasses and 79.5 +/- 12% for ePTFE
      bypasses (p = 0.26). In our experience, there was no statistically significant
      difference in long-term outcome of femoral above-knee popliteal artery bypass
      using autologous vein grafts or prosthetic ePTFE grafts.

PMID- 14670019
TI  - Changes in the proximal neck of abdominal aortic aneurysms early after
      endovascular treatment.
AB  - Long-term success of endovascular treatment of infrarenal abdominal aortic
      aneurysms (AAA) depends on secure "attachment" of the stent to the proximal and
      distal necks of the aneurysm. The purpose of this retrospective study was to
      detect changes in the proximal neck early after endovascular treatment of
      infrarenal AAA. Between November 1997 and December 1998, we performed
      endovascular treatment of infrarenal AAA in 43 patients. A bifurcated modular
      stent (AneuRx by Medtronic) was used in all patients. An oversized stent with a
      diameter 10% greater than the preoperative diameter of the proximal neck of the
      AAA was used in all cases. Follow-up examinations were carried out at 1, 6, and
      12 months using plain roentgenography, color Doppler ultrasound, and CT scan with
      contrast injection. Statistical analysis was performed using the Student's t
      test. Deterioration of the aortic neck is the result of a variety of mechanisms.
      The natural history of the infrarenal neck of AAA following endovascular repair
      (as well as conventional open repair) is progressive enlargement. Stenting could
      be an added risk factor for expansion. Strict follow-up is essential for early
      detection of this complication.

PMID- 14670020
TI  - Vascular reconstruction in limbs associated with resection of tumors.
AB  - Patients with tumors in limbs who undergo surgical treatment may present
      involvement of major vessels. The artery must be reconstructed for limb salvage
      and the vein may be reconstructed to avoid the onset of venous hypertension. The
      objective of this study was to analyze the results from surgical treatment of
      tumors associated with vascular reconstruction in limbs. A prospective follow-up
      was made of 17 patients with tumors involving major vessels in limbs who
      underwent vascular reconstruction. Arterial and venous reconstructions were
      performed in nine patients, arterial reconstruction was performed in six, and
      venous reconstruction in two patients. The vascular substitutes used were greater
      saphenous vein (19), expanded polytetrafluoroethylene prosthesis (5), and Dacron
      prosthesis (2). Vascular complications occurred in seven patients: one arterial
      graft rupture, three venous graft occlusions, and lymphedema in five patients.
      The following nonvascular complications occurred in 10 patients: pulmonary
      metastasis (7), local recurrence (2), neurological deficit (2), infection (2),
      partial necrosis of the flap (1), and enteric fistula (1). Six patients with
      pulmonary metastasis died. One patient underwent transfemoral amputation. Major
      vessel reconstruction in limbs associated with resection of neoplasms is a safe
      procedure. Venous revascularization should be performed using an autologous
      substitute.

PMID- 14670022
TI  - The impact of introducing an autologous intraoperative transfusion device to a
      community hospital.
AB  - The purpose of this study was to determine the benefits and disadvantages of
      transfusing autologous blood during abdominal aortic aneurysm (AAA) surgery at a
      district general hospital with an intraoperative autologous transfusion device
      (Haemoccel ABT 350). In this retrospective study, 128 patients underwent
      abdominal aortic aneurysm repair between 1992 and 1999 by a single vascular
      surgeon. Ninety-three patients (60 autologous and 33 allogeneic) had elective AAA
      repair (group A) and 25 patients (4 autologous and 21 allogeneic) had emergency
      AAA repair (group B). Nine group A patients (7.6%) received their own salvaged
      blood and no other allogeneic blood. Although the mean estimated blood loss was
      higher in the autologous group of patients (NS), the intraoperative autologous
      transfusion device did not significantly reduce allogeneic blood usage in
      patients who had autologous transfusion in both elective and emergency groups.
      There was no difference in postoperative hemoglobin and hematocrit, ICU stay or
      hospital stay. In this study, red cell salvage was significantly more expensive
      than blood bank usage (p < 0.0001), yet it did not significantly reduce the needs
      of allogeneic blood. We concluded that the intraoperative autologous transfusion
      device is underused, not cost-effective and requires formulation of local
      guidelines.

PMID- 14670021
TI  - Transcatheter embolization of extremity vascular malformations: the long-term
      success of multiple interventions.
AB  - Vascular malformations of the extremities present a difficult therapeutic
      challenge. Ligation of feeding vessels may lead to tissue necrosis and limb loss
      and can make subsequent attempts at transcatheter therapy impossible. The purpose
      of this study was to review our results with transcatheter embolization therapy
      in symptomatic vascular malformations in the upper and lower extremities in 50
      patients. A retrospective review was conducted of a computerized database of all
      patients undergoing transcatheter therapy of peripheral vascular malformations at
      our institution. The mean age of the patients was 22 years (range 1-51 years),
      and 34% were male. The most common presenting symptoms included pain (80%),
      swelling (68%), ulceration or distal ischemia (18%), and hemorrhage (6%).
      Previous unsuccessful surgical treatment or embolization had been performed in
      24% and 18% of patients, respectively. Predominantly venous lesions were treated
      by sclerotherapy with injection of ethanol. Arteriovenous and arterial lesions
      were treated by embolization via the arterial branch feeding vessels with
      cyanoacrylate. The most common vessels involved and treated were branches of the
      profunda femoris and tibial arteries (83% of lower extremity lesions), and
      branches of the brachial and radial arteries (82% of upper extremity lesions).
      Patients required a mean of 1.6 embolization procedures (range 1-5) over a mean
      period of 57 months. Sixteen patients (32%) underwent more than one embolization
      procedure. Of these, one was a planned staged procedure and 15 were performed
      secondary to residual or recurrent symptoms. Adjunctive surgical procedures were
      performed subsequent to embolization in three cases (6%). Ninety-two percent of
      patients remained asymptomatic or improved at a mean follow-up of 56 months.
      There was one case of limb loss (2%). Diffuse extremity vascular malformations
      are difficult to eradicate completely and recurrences are common. Although
      patients may require multiple embolization procedures and occasional adjunctive
      surgical resection, directed transcatheter embolization should be the treatment
      of choice for symptomatic extremity vascular malformations.

PMID- 14670023
TI  - Angioplasty and primary stenting of high-grade, long-segment superficial femoral
      artery disease: is it worthwhile?
AB  - The purpose of this study was to determine the long-term results and efficacy of
      angioplasty and stenting of long-segment, high-grade superficial femoral artery
      disease. Seventy-three consecutive primary balloon angioplasty procedures with
      immediate stenting in 70 patients with SVS/ISCVS grade B2 or C superficial
      femoral artery (SFA) disease exceeding 5 cm in length were evaluated. The mean
      lesion length was 16 cm and occlusion constituted 62%, with a runoff score of 8.
      Forty-nine procedures (67%) were performed for critical ischemia. A total of 135
      stents were placed. Follow-up was with 3-month duplex ultrasound; stenosis >50%
      was considered the end point for failure. Mean follow-up time was 26 months.
      Initial technical success with intent to treat was 90%. Initial success according
      to anatomic, hemodynamic, and clinical criteria was 90%, 88%, and 88%,
      respectively, with intent to treat. Limb salvage in the critical ischemia group
      was 71%. Overall cumulative primary patency rates at 12, 24, and 48 months were
      56%, 35%, and 22%, and secondary patency rates were 69%, 47%, and 37%,
      respectively. A stented segment length >10 cm and procedure in claudicants
      incurred an inferior patency rate. Treatment of high-grade SFA lesions with
      angioplasty and primary setting results in lower long-term patency rate than
      those with surgery, but combined with secondary interventions this treatment
      option may be an acceptable alternative in selected patients with critical
      ischemia. Femoropopliteal bypass remains the procedure of choice.

PMID- 14670024
TI  - Large vessel injury following operation for a herniated lumbar disc.
AB  - Major vascular injury can occur during an operation for a herniated lumbar disc
      due to the intimate anatomical relation between the lumbar vertebrae and major
      vessels. Although occurrence is infrequent, it is associated with high morbidity
      and mortality. Diagnosis is suspected when early signs of retroperitoneal
      hemorrhage appear, but may often be delayed for weeks or years. Formation of a
      pseudoaneurysm or an arteriovenous (A-V) fistula may be of gradual onset and
      produce initially only a few symptoms. We report here six cases of large vessel
      injury, which consisted of active bleeding from an injured common iliac artery,
      or a pseudoaneurysm of the common iliac artery with or without an A-V fistula
      that occurred following an operation for a herniated lumbar disc and was
      successfully treated by radiologic intervention and/or surgery. Angiography with
      the intention of intervention is considered the first step of treatment for a
      large vessel injury following an operation for a herniated lumbar disc at the
      level between fourth and fifth lumbar or between fifth lumbar and first sacral
      intervertebral space.

PMID- 14670025
TI  - Aneurysmal degeneration of the superficial femoral artery following stenting: an
      uncommon infectious complication.
AB  - Infrainguinal angioplasty and stenting is becoming a more commonly performed
      procedure. Its durability remains a matter of debate, however. Aneurysmal
      degeneration following angioplasty and stenting is a complication not previously
      described in the literature with regard to the superficial femoral artery. We
      present a case in which two aneurysms of the superficial femoral artery developed
      following angioplasty and multiple-stent placements in a patient who had
      previously undergone a failed femoral-to-below-the-knee popliteal artery PTFE
      bypass graft. The patient presented to our institution with an occluded, infected
      bypass graft. He was treated with graft and femoral artery/stent excision and
      vein bypass grafting. A brief review of infectious complications after stent
      placement is included.

PMID- 14670026
TI  - Relief of iliofemoral vein occlusion with the Palma bypass in a patient with
      Klippel Trenaunay syndrome.
AB  - Klippel Trenaunay syndrome is usually managed conservatively with surgery
      reserved for patients with symptomatic but mild cosmetic deformity or persistent
      venous hypertension despite nonoperative measures. Deep venous reconstruction is
      necessary in a small group of patients who present with significant chronic
      venous insufficiency due to hypoplastic, absent, or occluded deep venous outflow.
      Most often, venous outflow occlusion results from inadequate or surgically
      removed superficial collateral veins or from complications of endovascular
      procedures. In this article, we review the English-language literature and the
      Mayo Clinic experience, and report on a patient with Klippel Trenaunay syndrome
      who developed symptomatic iliofemoral venous occlusion following iliac vein
      stenting, which was successfully treated with a crossover saphenofemoral vein
      (Palma) bypass.

PMID- 14670027
TI  - Carotid embolectomy in the treatment of a paradoxical embolus.
AB  - Development of a paradoxical embolus to the carotid circulation through a patent
      foramen ovale is uncommon but well documented. Previous surgical experience with
      this entity is limited. Treatment for this condition typically involves
      anticoagulation or the use of an inferior vena cava filter with concurrent
      closure of the patent foramen itself. We report successful surgical treatment of
      a woman with a paradoxical embolus lodged in her left carotid artery. In
      addition, we provide a brief review of this rare topic and treatment rationale.

PMID- 14670028
TI  - Proximal left subclavian artery aneurysm presenting hemoptysis, hoarseness, and
      diplopia: repair through partial cardiopulmonary bypass and perfusion of the left
      common carotid artery.
AB  - Isolated true aneurysm of the subclavian artery is rare and can rupture,
      thrombose, embolize, or cause symptoms by local compression. We describe a case
      of a 67-year-old man with proximal left subclavian artery aneurysm presenting
      with hemoptysis, hoarseness, and diplopia. These symptoms suggested that the
      aneurysm ruptured, that the left recurrent laryngeal nerve was compressed by it,
      and that its mural thrombus caused cerebral embolism. It was incidentally
      confirmed that the aneurysm grew at the rate of 1.31 cm/year, from 3.0 to 4.2 cm
      in diameter for 11 months, preciously measured in a computed tomography scan. The
      aneurysm was successfully repaired via partial cardiopulmonary bypass and
      separate perfusion of the left common carotid artery through cross-clamping the
      descending thoracic aorta and the aortic arch between the origins of the
      brachiocephalic artery and the left common carotid artery. Neither partial
      clamping of the aortic arch at the portion branching the left subclavian artery
      nor taping the aortic arch between the origins of the left common carotid artery
      and the left subclavian artery could be achieved.

PMID- 14670029
TI  - Ruptured abdominal aortic aneurysms due to Salmonella, not of typhi species.
AB  - Ruptured aortic aneurysms due to Salmonella not of typhi species are rare and
      associated with high morbidity and mortality. We present three patients with
      Salmonella-infected ruptured aortic aneurysms successfully treated with an in
      situ prosthetic bypass graft. One patient had a saccular aneurysm at the
      infrarenal aorta and two patients had fusiform aneurysms at the aortic
      bifurcation. All the patients were treated with wide debridement of the infected
      aortic tissue followed by in situ graft replacement and long-term systemic
      antibiotic therapy. The method of revascularization, in situ bypass or
      extraanatomic bypass, remains controversial. On the basis of our clinical
      experience and recent literature focusing on more than 10 cases, in situ bypass
      reconstruction may be a feasible surgical technique for Salmonella-infected
      ruptured aortic aneurysm.

PMID- 14670030
TI  - Surgery on varicose veins in the early Ottoman period performed by Serefeddin
      Sabuncuoglu.
AB  - Serefeddin Sabuncuoglu, a pioneer of surgery, is known to be the author of first
      illustrated surgery textbook, Cerrahiyyetu'l Haniyye (Imperial Surgery), which
      was written in Turkish in 1465 AD at the age of 80 years. The purpose of this
      article is to describe his contributions to varicose vein surgery. In addition to
      vascular surgery, Serefeddin Sabuncuoglu was interested in a wide range of
      surgical specialities including thoracic surgery, general surgery, pediatric
      surgery, ophthalmology, orthopedic surgery, urologic surgery, and obstetrics and
      gynecology. His book was the first illustrated textbook of surgery in the Turkish
      medical literature, containing color illustrations of surgical procedures,
      incisions, and instruments. The book has been known of for only the past 60
      years. There are 137 different medical observations and recommendations in
      Cerrahiyyetu'l Haniyye, along with translated passages from the works of Ebu
      Kasim-ul Zahravi (Albucasis), Al-Tasrif (Textbook of Surgery), including
      Sabuncuoglu's additional original contributions. In chapter 90 of the book,
      Sabuncuoglu describes lower extremity varices and their surgical treatment and
      provides a few color illustrations. Although not recognized and rewarded in his
      time, Serefeddin Sabuncuoglu was a great surgeon in Turkish-Islamic medical
      history. This review demonstrates that his textbook, Cerrahiyyetu'l Haniyye, was
      the first illustrated textbook including various surgical procedures, incisions,
      and instruments of varicose vein surgery.

PMID- 14670032
TI  - Cancer vaccines 2003. Cancer and HIV vaccines: shared lessons. October 1 - 3,
      2003, New York, USA. Abstracts.

PMID- 14670031
TI  - Endovascular stent grafting of thoracic aortic aneurysms.
AB  - In an effort to decrease the morbidity of conventional open thoracic aortic
      aneurysm repair, we have witnessed in the last 10 years an expansion in the use
      of stent grafts as an alternative treatment option. This approach has provided a
      treatment option for patients with multiple medical comorbidities who may
      otherwise have been considered excessively high risk for standard open
      reconstruction. Results have identified promising procedural success while
      limiting complications and mortality rates. A review of contemporary results as
      well as patient and device characteristics is the focus of this article.

PMID- 14670033
TI  - On-chip hydrodynamic chromatography separation and detection of nanoparticles and
      biomolecules.
AB  - For the first time, on-chip planar hydrodynamic chromatography is combined with
      UV absorption detection. This technique is suitable for size characterization of
      synthetic polymers, biopolymers, and particles. Possible advantages of an on-chip
      hydrodynamic chromatography system over conventional techniques, such as size
      exclusion chromatography, and field-flow fractionation are fast analysis, high
      efficiency, reduced solvent consumption, and easy temperature control. The
      hydrodynamic separations are performed in a planar configuration realized in
      fused silica using a mixture of fluorescent and nonfluorescent polystyrene
      particles with sizes ranging from 26 to 155 nm. The planar chip configuration
      consists of a 1-microm-high, 0.5-mm-wide, and 69-mm-long channel, an integrated
      150-pL injection structure, and a 30-microm-deep and 30-microm-wide detection
      cell, suitable for UV absorption detection. By combination of the separation data
      obtained in the new fused-silica chip with those obtained using a previously
      presented planar hydrodynamic chromatography chip, which was realized using
      silicon and glass microtechnology, a description of the retention and dispersion
      behavior of planar hydrodynamic chromatography is obtained. Especially the
      influence of the sidewalls on the dispersion is investigated. Furthermore a
      hydrodynamic separation within 70 s of several biopolymers is shown in the glass
      silicon chip.

PMID- 14670034
TI  - Separation of plutonium and neptunium species by capillary electrophoresis
      inductively coupled plasma-mass spectrometry and application to natural
      groundwater samples.
AB  - Capillary electrophoresis (CE) was coupled to ICPMS in order to combine the good
      performance of this separation technique with the high sensitivity of the ICPMS
      for the analysis of plutonium and neptunium oxidation states. The combination of
      a fused-silica capillary with a MicroMist AR 30-I-FM02 nebulizer and a Cinnabar
      small-volume cyclonic spray chamber yielded the best separation results. With
      this setup, it was possible to separate a model element mixture containing
      neptunium (NpO2(+)), uranium (UO2(2+)), lanthanum (La3+), and thorium (Th4+) in 1
      M acetic acid. The same conditions were also suitable for the separation of
      various oxidation states of plutonium and neptunium in different aqueous samples.
      All separations were obtained within less than 15 min. A detection limit of 50
      ppb identical with 2 x 10(-7) M (3-fold standard deviation of a blank) was
      achieved. To prove the negligible disturbance of the plutonium and neptunium
      redox equilibria during the CE separations, plutonium and neptunium speciation by
      CE-ICPMS in acidic solutions was compared with the results of UV/visible
      absorption spectroscopy and was found to be in good agreement. The CE-ICPMS
      system was also applied to study the reduction of Pu(VI) in a humic acid
      containing groundwater at different pH values.

PMID- 14670035
TI  - Characterization of a variant of the spinach PSII type I light-harvesting protein
      using kinetically controlled digestion and RP-HPLC-ESI-MS.
AB  - A previously unknown isoform of the type I major antenna protein of photosystem
      II of spinach was identified, and its amino-terminal sequence was characterized
      by a novel kinetic digestion approach, in which sequential tryptic digestion was
      followed by analysis of both released peptides and truncated proteins by reversed
      phase high-performance liquid chromatography-electrospray ionization mass
      spectrometry. Using nonpolar, monolithic, 200-microm-i.d. separation columns
      based on poly(styrene/divinylbenzene) copolymer and applying gradients of
      acetonitrile in 0.05% aqueous trifluoroacetic acid, released peptides and
      truncated proteins could be separated and mass analyzed in a single
      chromatographic run. This enabled a straightforward identification of the
      fragments removed from the amino-terminal ends of the protein, which was
      essential for the characterization of the antenna isomers showing the most
      significant sequence variation in the amino-terminal region. The sequences of the
      amino termini were derived from the differences in molecular mass between intact
      and truncated proteins and were corroborated by sequencing using tandem mass
      spectrometry and database searching. The sequence of the 23 amino-terminal
      residues of the previously unknown isoform differed from that of the other two
      known isoforms only in one and three amino acids, respectively. Such subtle
      changes in amino acid sequence are supposed to play an important role in the
      supramolecular organization of photosynthetic antenna proteins.

PMID- 14670036
TI  - Characterization and evaluation of C18 HPLC stationary phases based on ethyl
      bridged hybrid organic/inorganic particles.
AB  - The characterization and evaluation of three novel 5-microm HPLC column packings,
      prepared using ethyl-bridged hybrid organic/inorganic materials, is described.
      These highly spherical hybrid particles, which vary in specific surface area
      (140, 187, and 270 m(2)/g) and average pore diameter (185, 148, and 108 A), were
      characterized by elemental analysis, SEM, and nitrogen sorption analysis and were
      chemically modified in a two-step process using octadecyltrichlorosilane and
      trimethylchlorosilane. The resultant bonded materials had an octadecyl surface
      concentration of 3.17-3.35 micromol/m(2), which is comparable to the coverage
      obtained for an identically bonded silica particle (3.44 micromol/m(2)) that had
      a surface area of 344 m(2)/g. These hybrid materials were shown to have
      sufficient mechanical strength under conditions normally employed for traditional
      reversed-phase HPLC applications, using a high-pressure column flow test. The
      chromatographic properties of the C(18) bonded hybrid phases were compared to a
      C(18) bonded silica using a variety of neutral and basic analytes under the same
      mobile-phase conditions. The hybrid phases exhibited similar selectivity to the
      silica-based column, yet had improved peak tailing factors for the basic
      analytes. Column retentivity increased with increasing particle surface area.
      Elevated pH aging studies of these hybrid materials showed dramatic improvement
      in chemical stability for both bonded and unbonded hybrid materials compared to
      the C(18) bonded silica phase, as determined by monitoring the loss in column
      efficiency through 140-h exposure to a pH 10 triethylamine mobile phase at 50
      degrees C.

PMID- 14670037
TI  - Analysis of metal ions by sweeping via dynamic complexation and cation-selective
      exhaustive injection in capillary electrophoresis.
AB  - To improve the detection sensitivity of metal ions in capillary zone
      electrophoresis (CZE), a novel method that combines complex formation and on-line
      sample preconcentration by sweeping was developed. Sweeping is defined as the
      picking and accumulating of analytes by a carrier in the background solution,
      with which they have considerable affinity. In this sweeping method, using
      ethylenediaminetetraacetic acid as carrier, dynamic complexation to form a UV
      absorbing chelate and on-line preconcentration occur simultaneously during a run.
      The technique was validated in terms of the limit of detection, reproducibility,
      and sensitivity enhancement. Detection responses of some divalent metal ions, in
      terms of peak heights, were improved from 60- to 180-fold, relative to
      conventional CZE which employed precapillary complexation. The limits of
      detection were in the range of (1.8-23.4) x 10(-8) M. This method was applied to
      the analysis of trace metal ions in factory wastewater. Furthermore, sweeping in
      conjunction with sample stacking accompanying electrokinetic injection, cation
      selective exhaustive injection (CSEI-sweeping), was also examined. Up to 140 000
      fold improvement in detector responses for some divalent and trivalent metal ions
      was realized by CSEI-sweeping. The limits of detection were in the range (2.4
      25.2) x 10(-11) M.

PMID- 14670038
TI  - Solid-phase extraction of amphiphiles based on mixed hemimicelle/admicelle
      formation: application to the concentration of benzalkonium surfactants in sewage
      and river water.
AB  - The capability of surfactant-coated mineral oxides to aid the solid-phase
      extraction (SPE) of amphiphiles based on the formation of mixed
      hemimicelles/admicelles was investigated. The approach is illustrated by studying
      the adsolubilization of benzalkonium homologue (C(12), C(14), C(16)) surfactants
      (BAS) on sodium dodecyl sulfate (SDS)-coated alumina. These oppositely charged
      surfactants form mixed aggregates on alumina causing retention of BAS by strong
      hydrophobic and ionic interactions. The recovery of BAS was found quantitative
      and independent of the alkyl chain length under a wide range of experimental
      conditions (3-200 mg of SDS/g of alumina; pH 2-11; sample flow rate 3-20 mL/min,
      and sample loading volume 0.025-1 L). Anionic and nonionic surfactants and
      electrolytes did not interfere to the levels found in raw sewage. Combination of
      BAS adsolubilization-based SPE with liquid chromatography/electrospray ionization
      in positive ion mode/ion trap mass spectrometry permitted the quantification of
      BAS with detection limits of 4 ng/L and their identification by isolation and
      subsequent fragmentation in the ion trap. The approach developed was applied to
      the determination of BAS in raw and treated sewage and river samples. The
      concentrations of benzalkonium surfactants found ranged between 0.1 and 49
      microg/L.

PMID- 14670039
TI  - Real-time determination of picomolar free Cu(II) in seawater using a fluorescence
      based fiber optic biosensor.
AB  - We report real-time, in situ determination of free copper ion at picomolar levels
      in seawater using a fluorescence-based fiber optic biosensor. The sensor
      transducer is a protein molecule, site-specifically labeled with a fluorophore
      that is attached to the distal end of an optical fiber, which binds free Cu(II)
      with high affinity and selectivity. The transducer reports the metal's
      concentration as a change in fluorescence intensity or lifetime, using a
      frequency domain approach. The transducer's response time is diffusion-limited,
      with a typical measurement requiring 30 s. The sensor demonstrates a detection
      limit of 0.1 pM free Cu(II) in a seawater model. Accuracy and precision of the
      sensor were at least comparable to cathodic ligand exchange/adsorptive cathodic
      stripping voltammetry. Measurements of tidal flushing of a copper-contaminated
      inlet are shown.

PMID- 14670040
TI  - Electrophoresis-assisted active immunoassay.
AB  - An active assay can be defined as that in which diffusion-controlled reactions
      are replaced by active delivery of analytes to probe molecules. The present paper
      describes an electrophoresis-assisted version of an active ELISA performed in
      tubes or wells with a dialysis membrane attached to their bottoms. The
      permeability of such a membrane to small ions allows us to apply electric field
      perpendicular to the membrane surface and to rapidly transport and concentrate
      charged macromolecular analytes in its vicinity. Probe molecules were either
      adsorbed or covalently linked to a modified surface of a membrane from
      regenerated cellulose. An active assay was performed both in separate cells and
      in 96-well microplates. It was demonstrated that the active assay format allows
      one (i) to reduce assay time to minutes instead of hours, (ii) to increase
      sensitivity by a factor of 10-300, and (iii) to capture within 10 min up to 70%
      of all the analyte molecules present in 0.36 mL of solution.

PMID- 14670041
TI  - Simultaneous measurement of urinary bisphenol A and alkylphenols by automated
      solid-phase extractive derivatization gas chromatography/mass spectrometry.
AB  - Bisphenol A (BPA) and alkylphenols (APs) are widely used industrial chemicals.
      BPA is used to manufacture polycarbonate plastic and epoxy resins; APs are used
      to make alkylphenol ethoxylates, common nonionic surfactants. BPA and APs can
      leach into the environment during industrial production and after degradation of
      the polycarbonate plastics and nonionic surfactants. Environmental exposure to
      these phenolic compounds has been associated with adverse reproductive and
      developmental effects in wildlife. We developed a sensitive and robust method for
      measuring BPA and six APs; 3-tert-butylphenol, 4-tert-butylphenol, 4-n
      octylphenol, 4-tert-octylphenol, 4-n-nonylphenol, and technical-grade nonylphenol
      in urine. The method is based on the use of automated solid-phase extraction
      (SPE) coupled to isotope dilution-gas chromatography/mass spectrometry (GC/MS).
      During the automated SPE process, the phenols are both extracted from the urine
      matrix and derivatized, using pentafluorobenzyl bromide, on commercially
      available styrene-divinylbenzene copolymer-based SPE cartridges. After elution
      from the SPE column, the derivatized phenols in the SPE eluate are analyzed by
      GC/MS. The method, validated on spiked pooled urine samples and on urine samples
      from exposed persons, has limits of detection of approximately 0.1 ng in 1 mL of
      urine.

PMID- 14670042
TI  - Improved beta-elimination-based affinity purification strategy for enrichment of
      phosphopeptides.
AB  - Alkaline-induced beta-elimination of phosphate from phosphoserine and
      phosphothreonine residues followed by addition of an affinity tag has recently
      been pursued as a strategy for enriching phosphorylated species from complex
      mixtures. Here we report the use of an introduced thiol tag as the ligand for
      affinity purification via disulfide exchange with an activated thiol resin and
      the development of a protocol to improve the sensitivity considerably over
      previous reports (i.e., to subpicomole levels.) During our experiments, we
      observed a side reaction in which water was eliminated from unmodified serine
      residues. This side reaction resulted in the introduction of the affinity tag
      into unphosphorylated proteins, confounding attempts to specifically purify
      phosphoproteins from mixtures. Unchecked, this side reaction will also prevent
      application of the beta-elimination strategy to phosphopeptide samples where the
      phosphorylated species are minor components (i.e., most current phosphoproteomics
      applications). Quantitation of the side reaction products using three synthetic
      unphosphorylated peptides showed varying conversion efficiencies; at maximum,
      1.7% of unphosphorylated peptide was converted to the affinity-tagged form.
      Inclusion of EDTA into the reaction reduced the side reaction but also greatly
      reduced the conversion efficiency of one of the phosphoserine residues of
      ovalbumin, suggesting a role for trace metal ions in the beta-elimination
      chemistry. Despite the presence of the side reaction, the affinity strategy was
      shown to be effective at enriching phosphopeptides from fairly complex peptide
      mixtures. The strategy was applied to the analysis of in vitro phosphorylation of
      bovine synapsin I by Ca(2+)/calmodulin-dependent kinase II, resulting in the
      identification of four phosphorylation sites, two of which have not been
      previously reported.

PMID- 14670043
TI  - Development of a sheathless interface between reversed-phase capillary HPLC and
      ICPMS via a microflow total consumption nebulizer for selenopeptide mapping.
AB  - A sheathless interface based on a total consumption micronebulizer operating at
      flow rates in the range 0.5-7.5 microL min(-1) was developed between capillary
      HPLC and ICPMS. It allowed the efficient nebulization and transport into the
      plasma of mobile phases containing up to 100% organic solvent without either
      cooling the spray chamber or oxygen addition. The coupled system was applied to
      selenopeptide mapping in a protein fraction isolated from a selenized yeast
      extract. The detection limits were 150 (80Se) and 200 fg (82Se) for a quadrupole
      instrument with and without a collision cell, respectively, which is a factor 100
      150 less than that reported elsewhere for HPLC-ICPMS. The minimal peak broadening
      ( approximately 5 s at the half-height) allowed baseline resolution of a mixture
      containing more than 30 selenopeptides, many of which could not be separated
      using the conventional HPLC-ICPMS coupling.

PMID- 14670044
TI  - Stable-isotope dimethyl labeling for quantitative proteomics.
AB  - In this paper, we report a novel, stable-isotope labeling strategy for
      quantitative proteomics that uses a simple reagent, formaldehyde, to globally
      label the N-terminus and epsilon-amino group of Lys through reductive amination.
      This labeling strategy produces peaks differing by 28 mass units for each
      derivatized site relative to its nonderivatized counterpart and 4 mass units for
      each derivatized isotopic pair. This labeling reaction is fast (less than 5 min)
      and complete without any detectable byproducts based on the analysis of MALDI and
      LC/ESI-MS/MS spectra of both derivatized and nonderivatized peptide standards and
      tryptic peptides of hemoglobin molecules. The intensity of the a(1) and y(n-1)
      ions produced, which were not detectable from most of the nonderivatized
      fragments, was substantially enhanced upon labeling. We further tested the method
      based on the analysis of an isotopic pair of peptide standards and a pair of
      defined protein mixtures with known H/D ratios. Using LC/MS for quantification
      and LC/MS/MS for peptide sequencing, the results show a negligible isotopic
      effect, a good mass resolution between the isotopic pair, and a good correlation
      between the experimental and theoretical data (errors 0-4%). The relative
      standard deviation of H/D values calculated from peptides deduced from the same
      protein are less than 13%. The applicability of the method for quantitative
      protein profiling was also explored by analyzing changes in nuclear protein
      abundance in an immortalized E7 cell with and without arsenic treatment.

PMID- 14670045
TI  - Ligand-exchange detection of phosphorylated peptides using liquid chromatography
      electrospray mass spectrometry.
AB  - Electrospray ionization mass spectrometry (ESI-MS) is used to selectively detect
      analytes with a high affinity for metal ions. The detection method is based on
      the selective monitoring of a competing ligand at its specific m/z value that is
      released during the ligand-exchange reaction of a metal-ligand complex with
      analyte(s) eluting from a reversed-phase liquid chromatography column. The ligand
      exchange reaction proceeds in a postcolumn reaction detection system placed prior
      to the inlet of the electrospray MS interface. The feasibility of metal affinity
      detection by ESI-MS is demonstrated using phosphorylated peptides and
      iron(III)methylcalcein blue as reactant, as a model system. Methylcalcein blue
      (MCB) released upon interaction with phosphorylated peptides is detected at m/z
      278. The ligand-exchange detection is coupled to a C8 reversed-phase column to
      separate several nonphosphorylated enkephalins and the phosphorylated peptides
      pp60 c-src (P) and M2170. Detection limits of 2 microM were obtained for pp60 c
      src (P) and M2170. The linearity of the detection method is tested in the range
      of 2-80 micromol/L phosphorylated compounds (r(2) = 0.9996), and a relative
      standard deviation of less than 8% (n = 3) for all MCB responses of the different
      concentrations of phosphorylated compounds was obtained. The presented method
      showed specificity for phosphorylated peptides and may prove a useful tool for
      studying other ligand-exchange reactions and metal-protein interactions.

PMID- 14670046
TI  - Synthetic single-nanopore and nanotube membranes.
AB  - There is increasing interest in investigating transport and electrochemical
      phenomena in synthetic membrane samples that contain a single pore of nanoscopic
      diameter. Approaches used to date for preparing such single-nanopore membranes
      include microfabrication-based methods, the track-etch method, and a method based
      on the incorporation of a single fullerene nanotube within a synthetic membrane.
      We describe here an alternative approach that we believe is easier and more
      accessible than the previously described methods. This method is based on a very
      low pore density track-etch membrane obtained from commercial sources.
      Fluorescence microscopy is used to identify and isolate a single nanopore in this
      membrane. Membrane samples containing single nanopores with diameters as small as
      30 nm have been prepared. Furthermore, we show here that an electroless plating
      method can be used to deposit a gold nanotube within the single nanopore, and
      this provides a route for further decreasing the inside diameter of the pore. A
      single-nanotube membrane with an electrochemically determined inside diameter of
      approximately 2 nm was prepared and evaluated.

PMID- 14670047
TI  - Magnetic cell separation: characterization of magnetophoretic mobility.
AB  - Magnetic cell separation has become a popular technique to enrich or deplete
      cells of interest from a heterogeneous cell population. One important aspect of
      magnetic cell separation is the degree to which a cell binds paramagnetic
      material. It is this paramagnetic material that imparts a positive
      magnetophoretic mobility to the target cell, thus allowing effective cell
      separation. A mathematical relationship has been developed to correlate magnetic
      labeling to the magnetophoretic mobility of an immunomagnetically labeled cell.
      Four parameters have been identified that significantly affect magnetophoretic
      mobility of an immunomagnetically labeled cell: the antibody binding capacity
      (ABC) of a cell population, the secondary antibody amplification (psi), the
      particle-magnetic field interaction parameter (DeltachiV(m)), and the cell
      diameter (D(c)). The ranges of these parameters are calculated and presented
      along with how the parameters affect the minimum and maximum range of
      magnetophoretic mobility. A detailed understanding of these parameters allows
      predictions of cellular magnetophoretic mobilities and provides control of cell
      mobility through selection of antibodies and magnetic particle conjugates.

PMID- 14670048
TI  - Sample metallization for performance improvement in desorption/ionization of
      kilodalton molecules: quantitative evaluation, imaging secondary ion MS, and
      laser ablation.
AB  - The metallization procedure, proposed recently for signal improvement in organic
      secondary ion mass spectrometry (SIMS) (Delcorte, A.; Medard, N.; Bertrand, P.
      Anal.Chem. 2002, 74, 4955)., has been thoroughly tested for a set of kilodalton
      molecules bearing various functional groups: Irganox 1010, polystyrene,
      polyalanine, and copper phthalocyanine. In addition to gold, we evaluate the
      effect of silver evaporation as a sample treatment prior to static SIMS analysis.
      Ion yields, damage cross sections, and emission efficiencies are compared for Ag-
      and Au-metallized molecular films, pristine coatings on silicon, and
      submonolayers of the same molecules adsorbed on silver and gold. The results are
      sample-dependent but as an example, the yield enhancement calculated for
      metallized Irganox films with respect to untreated coatings is larger than 2
      orders of magnitude for the quasimolecular ion and a factor of 1-10 for
      characteristic fragments. Insights into the emission processes of quasimolecular
      ions from metallized surfaces are deduced from kinetic energy distribution
      measurements. The advantage of the method for imaging SIMS applications is
      illustrated by the study of a nonuniform coating of polystyrene oligomers on a
      100-microm polypropylene film. The evaporated metal eliminates sample charging
      and allows us to obtain enhanced quality images of characteristic fragment ions
      as well as reasonably contrasted chemical mappings for cationized PS oligomers
      and large PP chain segments. Finally, we report on the benefit of using metal
      evaporation as a sample preparation procedure for laser ablation mass
      spectrometry. Our results show that the fingerprint spectra of Au-covered
      polystyrene, polypropylene, and Irganox films can be readily obtained under 337
      nm irradiation, a wavelength for which the absorption of polyolefins is low. This
      is probably because the gold clusters embedded in the sample surface absorb and
      transfer the photon energy to the surrounding organic medium.

PMID- 14670049
TI  - Bacillus spore identification via proteolytic peptide mapping with a miniaturized
      MALDI TOF mass spectrometer.
AB  - An approach is tested here as a rapid screening method for Bacillus spore species
      employing bacterial peptide analysis with a miniaturized MALDI TOF mass
      spectrometer. A limited set of tryptic peptides was generated in situ following
      selective solubilization of the small, acid-soluble protein family (SASP) from
      spore samples on the MALDI sample holder. To facilitate species identification, a
      compact database was created comprising masses of the tryptic cleavage products
      generated in silico from all Bacillus and Clostridium SASPs whose sequences are
      available in public databases. Experimental measurements were matched against the
      custom-made database, and a published statistical model was then used to evaluate
      the probability of false identifications.

PMID- 14670050
TI  - Biosensing based on light absorption of nanoscaled gold and silver particles.
AB  - The absorption spectrum of noble metal spherical nanoparticles is known to be
      strongly influenced by the dielectric constant of the surrounding material, and
      as such, these particles are well suited for biosensing applications. To perform
      biosensing using nanoparticles on a substrate, the metal particles are covalently
      attached onto quartz using an organic adhesion layer of mercaptosilanes. The
      particles in solution are characterized by UV-vis spectroscopy and transmission
      electron microscopy, while those attached to the quartz are characterized with UV
      vis spectroscopy and atomic force microscopy. Antibodies are attached to the
      metal nanoparticles, and the antigen recognition is monitored via the change of
      light absorption when this binding event occurs. Not only is the absorbance
      originating from plasmon resonances of the particles influenced by the dielectric
      properties of molecules attached to the nanospheres but also the interband
      absorption of the particles changes, which will be demonstrated in this report. A
      light absorption change is detected when a molecular recognition occurs between
      the bioreceptor molecules attached to the nanoparticle and a biomolecular
      counterpart. This change in absorption can be very large when adhered molecules
      are at resonance (interband transitions). In addition, the presented type of
      biosensing can be a cost-effective and easy to use alternative to conventional
      biosensing techniques.

PMID- 14670051
TI  - Pore exclusion chromatography-inductively coupled plasma-mass spectrometry for
      monitoring elements in bacteria: a study on microbial removal of uranium from
      aqueous solution.
AB  - The interstitial spaces between spherical particles in a packed column can act as
      a sieve that passes microorganisms below a certain size. If the bed is a
      perfusion-type material (containing a binary distribution of large and small
      pores), colloidal-size microorganisms are subject only to pore exclusion, while
      all molecules are subject to size exclusion among the various pores. Thus,
      microorganisms elute first, followed by macromolecules, and then small molecules.
      Coupling this separation method to an ICP magnetic sector mass spectrometer
      provides a sensitive, direct means to study the microbial uptake of heavy metals
      (i.e., uranium) from their surrounding environments. Multiple metal ions can be
      monitored in the microorganism and in the surrounding solution. In this way,
      definitive information can be provided for the remediation of radioactive waste
      sites. The effect of uranium on microbial growth is also discussed.

PMID- 14670052
TI  - Using bioinspired thermally triggered liposomes for high-efficiency mixing and
      reagent delivery in microfluidic devices.
AB  - High-efficiency mixing is of fundamental importance for the successful
      development and application of lab-on-a-chip devices. In this report, we present
      the use of bioinspired thermally triggered liposomes for the controlled delivery
      and subsequent rapid mixing of reagents in a microfluidic device. In this
      technique, reagents are encapsulated inside the aqueous interior of liposomes
      that are dispersed evenly throughout a microfluidic system. Mixing of the
      encapsulated reagent and reaction do not occur until the reagent is released by a
      thermal trigger. This approach takes advantage of the dramatically increased
      lipid membrane permeability of liposomes near the gel-to-liquid phase transition
      temperature (T(m)) to deliver reagents at a precise location in the microfluidic
      device through the modulation of temperature. Implementation of this technique
      requires the encapsulation of the desired reagent in a liposome whose formulation
      has an appropriate T(m), as well as accurate spatial control of the temperature
      in the microfluidic device. As the liposomes are uniformly dispersed through the
      microfluidic channel, mixing occurs quite rapidly upon the release of the
      reagent. We demonstrate this technique by using several formulations of thermally
      triggered liposomes to release the hydrophilic fluorescent dyes at controlled
      locations in a polycarbonate microfluidic device. Additionally, we demonstrate a
      DNA labeling reaction using liposomes in a capillary-based microfluidic device.
      Under the conditions studied here, mixing and reaction are complete in
      approximately 200 microm of channel length. We believe this approach holds great
      promise for the performance of rapid high-throughput assays and in particular for
      biological analytes whose native environment is mimicked by the liposome.

PMID- 14670053
TI  - A correlation algorithm for the automated quantitative analysis of shotgun
      proteomics data.
AB  - Quantitative shotgun proteomic analyses are facilitated using chemical tags such
      as ICAT and metabolic labeling strategies with stable isotopes. The rapid high
      throughput production of quantitative "shotgun" proteomic data necessitates the
      development of software to automatically convert mass spectrometry-derived data
      of peptides into relative protein abundances. We describe a computer program
      called RelEx, which uses a least-squares regression for the calculation of the
      peptide ion current ratios from the mass spectrometry-derived ion chromatograms.
      RelEx is tolerant of poor signal-to-noise data and can automatically discard
      nonusable chromatograms and outlier ratios. We apply a simple correction for
      systematic errors that improves the accuracy of the quantitative measurement by
      32 +/- 4%. Our automated approach was validated using labeled mixtures composed
      of known molar ratios and demonstrated in a real sample by measuring the effect
      of osmotic stress on protein expression in Saccharomyces cerevisiae.

PMID- 14670054
TI  - Rotating disk potentiometry for inner solution optimization of low-detection
      limit ion-selective electrodes.
AB  - The extent of optimization of the lower detection limit of ion-selective
      electrodes (ISEs) can be assessed with an elegant new method. At the detection
      limit (i.e., in the absence of primary ions in the sample), one can observe a
      reproducible change in the membrane potential upon alteration of the aqueous
      diffusion layer thickness. This stir effect is predicted to depend on the
      composition of the inner solution, which is known to influence the lower
      detection limit of the potentiometric sensor dramatically. For an optimized
      electrode, the stir effect is calculated to be exactly one-half the value of the
      case when substantial coextraction occurs at the inner membrane side. In
      contrast, there is no stir effect when substantial ion exchange occurs at the
      inner membrane side. Consequently, this experimental method can be used to
      determine how well the inner filling solution has been optimized. A rotating disk
      electrode was used in this study because it provides adequate control of the
      aqueous diffusion layer thickness. Various ion-selective membranes with a variety
      of inner solutions that gave different calculated concentrations of the complex
      at the inner membrane side were studied to evaluate this principle. They
      contained the well-examined silver ionophore O,O' '-bis[2-(methylthio)ethyl]-tert
      butylcalix[4]arene, the potassium ionophore valinomycin, or the iodide carrier
      [9]mercuracarborand-3. Stir effects were determined in different background
      solutions and compared to theoretical expectations. Correlations were good, and
      the results encourage the use of such stir-effect measurements to optimize ISE
      compositions for real-world applications. The technique was also found to be
      useful in estimating the level of primary ion impurities in the sample. For an
      iodide-selective electrode measured in phosphoric acid, for example, apparent
      iodide impurity levels were calculated as 5 x 10(-10) M.

PMID- 14670055
TI  - Covalent immobilization of beta-galactosidase onto a gold-coated magnetoelastic
      transducer via a self-assembled monolayer: toward a magnetoelastic biosensor.
AB  - The enzyme beta-galactosidase has been covalently immobilized onto a gold-coated
      magnetoelastic film via a self-assembled monolayer (SAM) of omega-carboxylic acid
      alkylthiol. Use of magnetoelastic transduction allows for the wireless monitoring
      of enzymatic activity through the associated change in the frequency and
      amplitude of magnetic fields. The formations of SAMs of 3-mercaptopropanoic acid
      and thioctic acid were monitored by magnetoelastic transduction. After coupling
      of beta-galactosidase to the SAMs, the enzyme activity was monitored by using a
      substrate that forms an insoluble product upon action of the enzyme.
      Specifically, an indolyl galactopyranoside substrate was employed in conjunction
      with an azo dye as the precipitating system. The immobilized enzyme was evaluated
      and found to have an apparent Michaelis-Menten constant (KM) of 1.2 mM for the
      indolyl galactopyranoside. Calibration plots for both substrates and inhibitors
      were generated to establish the versatility of this sensing system. Kinetic
      parameters for nonprecipitating substrates were determined in conjunction with a
      precipitating enzymatic substrate by way of a competitive inhibition study using
      beta-galactosidase attached to magnetoelastic strips. The methods developed
      within this work allow for the fabrication of wireless enzyme sensing systems,
      which can also be used as another means of screening for enzyme inhibitors.

PMID- 14670056
TI  - Comparison of voltammetric data obtained for the trans
      [Mn(CN)(CO)2[P(OPh)3](Ph2PCH2PPh2)]0/+ process in BMIM.PF6 ionic liquid under
      microchemical and conventional conditions.
AB  - Conventional cyclic voltammetric studies on the oxidation of millimolar
      concentrations (mg masses) of trans-[Mn(CN)(CO)(2)[P(OPh)(3)](Ph(2)PCH(2)PPh(2))]
      (trans-Mn) dissolved in milliliter volumes of bulk ionic liquid, 1-butyl-3
      methylimidazolium hexafluorophosphate (BMIM.PF(6)), give rise to a reversible
      [trans-Mn](0/+) process. In this study, it is shown that equally well-defined
      reversible voltammetry can be more economically obtained under microchemical
      ionic liquid conditions by employing a chemically modified electrode (microg
      quantities of trans-Mn adhered to a glassy carbon electrode covered with
      microliter volumes of water-immiscible BMIM.PF(6)) in contact with aqueous (0.1 M
      KPF(6)) electrolyte. The ability to obtain electrochemical data that are directly
      relatable to bulk ionic liquid media under these microchemical conditions is
      principally associated with the dissolution of electrogenerated solid [trans
      Mn](+) in the layer of water-immiscible BMIM.PF(6) present at the electrode/ionic
      liquid/aqueous electrolyte interface. If the BMIM.PF(6) layer is sufficiently
      thick, mass transport of the dissolved species is governed by semi-infinite
      linear diffusion. Under these conditions, the voltammetric waveshape and
      position, but not the current magnitude are the same as those found when
      conventional bulk ionic liquid conditions are employed. In contrast, use of very
      thin layers produces voltammograms that exhibit the characteristics expected for
      a reversible process in which the mass transport process is predominantly
      governed by finite rather than semi-infinite diffusion. A theoretical model has
      been developed that describes the transformation from thick- to thin-layer type
      behavior as the thickness of the ionic liquid layer is decreased.

PMID- 14670057
TI  - Electrochemical characterization of binderless, recompressed exfoliated graphite
      electrodes: electron-transfer kinetics and diffusion characteristics.
AB  - Exfoliated graphite (EG) is prepared by the thermal exfoliation of graphite
      intercalation compounds at different temperatures. Surface and bulk
      physicochemical properties of EG are followed by spectroscopic and analytical
      methods and are observed to be a function of exfoliation temperature. EG
      particles can be recompressed without any binder and used as surface-renewable
      electrodes. Surface preparation is accomplished by either polishing or roughening
      the electrode surface using emery sheets. Effects of exfoliation temperature and
      the surface preparation on the electron-transfer kinetics and on the diffusion
      characteristics have been followed by electrochemical methods using several
      benchmark redox systems. It is found that the electron-transfer kinetics and the
      diffusion of K(4)[Fe(CN)(6)] are affected by the nature of the EG surface while
      that of iron(II)(1,10-phenanthroline)(3) and cobalt(II)(1,10-phenanthroline)(3)
      are not affected by the surface preparation. The redox systems are classified
      into different groups according to their kinetic sensitivity. Diffusion of
      electroactive species toward the EG electrodes is found to nonlinear. Current
      time plots suggest that the recompressed EG electrodes can be modeled as
      fractals.

PMID- 14670058
TI  - Characterization of pigment particle absorption efficiencies using frequency
      domain photon migration.
AB  - Time-dependent measurements of multiply scattered light were made using frequency
      domain photon migration (FDPM) techniques in polystyrene latex as a function of
      ppm pigment concentration (by weight) in order to determine the wavelength
      dependent absorption efficiencies for three different pigment particles. The
      results demonstrate that the absorption spectra of pigment particles within their
      dispersing vehicles concur with the complementary color chart. FDPM offers a
      first-principles method for assessing optical characteristics of pigments within
      their dispersing vehicles and without the need to resort to conventional
      measurement of diffuse reflectance from coatings and data analysis using
      phenomenological theory.

PMID- 14670059
TI  - Tilted brownian ratchet for DNA analysis.
AB  - In this paper, we report a factor of 3 improvement in the resolution and a factor
      of 10 improvement in the speed of fractionation of approximately 100-kb DNA
      molecules in Brownian ratchet arrays. In our device, the electrophoretic flow is
      tilted at a small angle relative to the array axis. Tilting accelerates the
      fractionation speed because a higher fraction of the diffusing molecules is
      "ratcheted" at each step in the array. Molecules of lengths 48.5 and 164 kb can
      be separated in approximately 70 min with a resolution of approximately 3.8,
      using a 12-mm-long array. The Brownian ratchet arrays are not limited to DNA
      separation, but can, in principle, be used for any particle in this size range.

PMID- 14670060
TI  - Macro-/nanoporous silicon as a support for high-performance protein microarrays.
AB  - The present work demonstrates the possibilities of using macroporous silicon as a
      substrate for highly sensitive protein chip applications. The formation of 3D
      porous silicon structures was performed by electrochemical dissolution of
      monocrystalline silicon. The fabricated macroporous silicon network has a rigid
      spongelike structure showing high uniformity and mechanical stability. The
      microfluidic properties of the substrates were found to be essential for a good
      bioassay performance. Small spot area, good spot reproducibility, and homogeneous
      spot profiles were demonstrated on the substrates for immobilized aRIgG. Water
      contact angles were measured on the porous surface and compared to that of planar
      silicon, silanized glass, and ordinary microscope glass slides. The effect of the
      porous surface on the performance of a model IgG-binding immunoassay is
      presented. aRIgG was microdispensed onto the chip surface forming a microarray of
      spots with high affinity for the target analyte. The dispensing was performed
      using an in-house-developed piezoelectric flow-through dispenser. Each spot was
      formed by a single droplet (100 pL) at each position. The macroporous silicon
      allowed a high-density microarraying with spot densities up to 4400 spots/cm2 in
      human plasma samples without cross-talk and consumption of only 0.6 pmol of
      antibodies/1-cm2 array. Antigen levels down to 70 pM were detected.

PMID- 14670061
TI  - Moment analysis of mass-transfer kinetics in C18-silica monolithic columns.
AB  - The moment analysis of elution peak profiles based on new moment equations
      provides information on the mass-transfer characteristics of C(18)-silica
      monolithic columns. The flow rate dependence of the HETP data was analyzed using
      the generalized van Deemter equation, after correction of these data by
      subtraction of the external mass-transfer contribution to band broadening.
      Kinetic parameters and diffusion coefficients related to the mass-transfer
      processes in monolithic columns were derived by taking advantage of the different
      flow velocity dependence of their contributions to band broadening. At high flow
      rates, axial dispersion and diffusive migration across the monolithic C(18)
      silica skeleton contribute much to band broadening, suggesting that it remains
      important to reduce the influence of eddy diffusion and the mass-transfer
      resistance in the stationary phase to achieve fast separations and a high
      efficiency. Surface diffusion plays a predominant role for molecular migration in
      the monolithic stationary phase. Although the value of the surface diffusion
      coefficient (D(s)) depends on an estimate of the external mass-transfer
      coefficient, D(s) values of the order of 10(-7) cm(2) s(-1) were calculated for
      the first time for the C(18)-silica monolithic skeleton. The value of D(s)
      decreases with increasing retention of sample compounds. Analysis of a kind of
      time constant calculated from D(s) suggests that the "chromatographic
      corresponding particle size" is approximately 4 microm for the C(18)-silica
      monolithic stationary phase used in this study. The accuracy of the D(s) values
      determined was discussed.

PMID- 14670062
TI  - Mapping of potential gradients within the electrospray emitter.
AB  - A novel electrochemical probe has been designed, built, and used to characterize
      the distribution in solution potential within the metal capillary and Taylor cone
      of the electrospray (ES) device. The measurement system consists of three
      electrodes-a counter electrode held at highly negative potential that serves as
      the cathode, and two anodes consisting of a disk-shaped, mobile, internal
      (working) electrode, and the internal surface of the surrounding ES capillary
      (auxiliary electrode, held at ground potential). One-dimensional differential
      electrospray emitter potential (DEEP) maps detailing solution potential gradients
      within the electrospray emitter and in the region of the Taylor cone are
      constructed by measuring the potential at the working electrode vs the ES
      capillary, as a function of working electrode position along the emitter axis.
      Results show that the measured potential difference increases as the internal
      probe travels toward the ES capillary exit, with values rising sharply as the
      base of the Taylor cone is penetrated. Higher conductivity solutions exhibit
      potentials of higher magnitude at longer distances away from the counter
      electrode, but these same solutions show lower potentials near the ES capillary
      exit. Removal of easily oxidizable species from the solution causes the measured
      potential difference to have nonzero values at distances further within the
      capillary, and the values measured at all points are raised. Results are
      consistent with the characterization of the electrospray system as a controlled
      current electrolytic flow cell. Elucidation of the electrochemical details of the
      electrospray process can lead to mass spectrometric signal enhancement of certain
      species present in the spraying liquid and also allow the detection of molecules
      that are usually not observable due to their low ionization efficiencies.

PMID- 14670063
TI  - Radiolytic modification of basic amino acid residues in peptides: probes for
      examining protein-protein interactions.
AB  - Protein footprinting utilizing hydroxyl radicals coupled with mass spectrometry
      has become a powerful technique for mapping the solvent accessible surface of
      proteins and examining protein-protein interactions in solution. Hydroxyl
      radicals generated by radiolysis or chemical methods efficiently react with many
      amino acid residue side chains, including the aromatic and sulfur-containing
      residues along with proline and leucine, generating stable oxidation products
      that are valuable probes for examining protein structure. In this study, we
      examine the radiolytic oxidation chemistry of histidine, lysine, and arginine for
      comparison with their metal-catalyzed oxidation products. Model peptides
      containing arginine, histidine, and lysine were irradiated using white light from
      a synchrotron X-ray source or a cesium-137 gamma-ray source. The rates of
      oxidation and the radiolysis products were primarily characterized by
      electrospray mass spectrometry including tandem mass spectrometry. Arginine is
      very sensitive to radiolytic oxidation, giving rise to a characteristic product
      with a 43 Da mass reduction as a result of the loss of guanidino group and
      conversion to gamma-glutamyl semialdehyde, consistent with previous metal
      catalyzed oxidation studies. Histidine was oxidized to generate a mixture of
      products with characteristic mass changes primarily involving rupture of and
      addition to the imidazole ring. Lysine was converted to hydroxylysine or
      carbonylysine by radiolysis. The development of methods to probe these residues
      due to their high frequency of occurrence, their typical presence on the protein
      surface, and their frequent participation in protein-protein interactions
      considerably extends the utility of protein footprinting.

PMID- 14670064
TI  - A strategy of plasma protein quantitation by selective reaction monitoring of an
      intact protein.
AB  - Immunoassays are used extensively in the quantitative analysis of proteins in
      plasma, urine, and other biological matrixes to support preclinical and clinical
      studies. Although immunoassays are both sensitive and rapid, difficulties during
      development of these assays are compounded by the need to have a specific
      antibody or antigen to the protein of interest. Furthermore, calibration curves
      of immunoassays are inherently nonlinear, and the technique often detects many
      structurally related components in addition to the analyte of interest. We have
      developed a novel strategy of analyzing protein concentrations in plasma by
      utilizing 96-well solid-phase extraction and LC-MS/MS detection of the intact
      protein. This strategy has been successfully applied in method development and
      assay validation of quantitatively analyzing protein rK5 concentrations in monkey
      plasma samples. Additional techniques such as precolumn regeneration and column
      heating were also incorporated into the assay. Total run time for each sample was
      approximately 15 min. An LLOQ of 99.2 ng/mL from a sample volume of 50 microL,
      corresponding to only 380 fmol (3.97 ng) of the rK5 analyte being injected onto
      the analytical column (assuming 100% extraction recovery), was obtained. The
      validated linear dynamic range was between 99.2 and 52 920.0 ng/mL, with a
      correlation coefficient (r(2)) ranging from 0.9972 and 0.9994. The intraassay CV
      for this assay was between 0.6 and 3.8%, and the interassay CV was between 1.7
      and 3.2%. Interassay mean accuracies were between 101.5 and 104.7%. The assay has
      proven rugged and specific and has been employed to generate data in support of
      preclinical studies. This strategy for rK5 assay could be used for the
      development of bioanalytical assays to provide preclinical and clinical support
      for other protein drug candidates and, furthermore, for the validation of
      biomarkers discovered from proteomic research.

PMID- 14670065
TI  - Graphite-coated nanoelectrospray emitter for mass spectrometry.
AB  - A new, more rapid method for coating nanoelectrospray emitters with graphite is
      to use a vacuum deposition chamber and a graphite carbon electrode. This method
      allows for mass production of nanoelectrospray emitters in a short period of
      time. The emitters are laser-pulled borosilicate glass micropipets and have
      tapers of around 4 microm i.d. The conductive coating applied to the emitter is
      only 20-30 nm thick, allowing for optical transparency with the borosilicate
      emitters. The conductive coating is stable for a number of hours at the high
      voltages used for nanoelectrospray ionization and is durable in both positive and
      negative ion modes-even during electrical discharge. This stability will make it
      possible to couple these emitters with online separations such as capillary
      liquid chromatography or capillary electrophoresis.

PMID- 14670066
TI  - Photoelectrocatalytic oxidation of o-phenols on copper-plated screen-printed
      electrodes.
AB  - A novel and sensitive detection method based on photoelectrocatalytic oxidation
      of o-diphenols was demonstrated on a copper-plated screen-printed carbon
      electrode (designated CuSPE) in pH 8 phosphate buffer solution. The o-diphenols
      can be detected amperometrically through electrochemical oxidation at a low
      applied potential of -0.1 V versus Ag/AgCl, where the CuSPE is much less subject
      to interfering reactions. The mechanism that induces good selectivity of the
      CuSPE is explained in terms of the formation of a cyclic five-member complex
      intermediate (Cu(II)-o-quinolate). A prototype homemade flow through cell design
      is described for incorporating the photoelectrode and light source. Electrode
      irradiation results in a large increase in anodic current. The oxidative
      photocurrents produced by irradiation increase with light intensity presumably
      because of the formation of semiconductor Cu(2)O. The principle used in this
      study has an opportunity to extend into various research applications.

PMID- 14670067
TI  - Differential charging in X-ray photoelectron spectroscopy: a nuisance or a useful
      tool?
AB  - We apply a negative bias to the sample while recording an XPS spectrum to enhance
      differential (positive) charging. The enhanced differential charging is due to
      the repulsion of stray electrons from the sample, which normally cause partial
      neutralization of the poorly conducting samples or regions accumulating positive
      charging, as a consequence of the photoelectron emission. This enhanced
      differential charging (obtained by negative biasing) is shown to have the ability
      to separate otherwise overlapping peaks of PDMS layer from that of the SiO(2)/Si
      substrate. Each layer experiences different charging that can be used to derive
      information related to dielectric properties of the layers, proximity of the
      atoms within composite multilayers, or both. Hence, differential charging in XPS,
      which is usually considered as a nuisance, is turned into a useful tool for
      extracting additional information from nanometer-size surface structures.

PMID- 14670068
TI  - Purification and characterization of thiols in an arsenic hyperaccumulator under
      arsenic exposure.
AB  - Pteris vittata (Chinese brake fern) is the first reported arsenic
      hyperaccumulator. To investigate the arsenic tolerance mechanism in this plant,
      reversed-phase HPLC with postcolumn derivatization was used to analyze the thiols
      induced under arsenic exposure. A major thiol in the plant leaflets was found to
      be responsive to arsenic exposure. The arsenic-induced compound was purified on a
      large scale by combining covalent chromatography and preparative reversed-phase
      HPLC. About 2 mg of this compound was isolated from 1 kg of fresh leaflets. The
      purified arsenic-induced compound was characterized using electrospray ionization
      mass spectrometry. A molecular ion (M + 1) of 540 and fragments were obtained,
      which indicated that the arsenic-induced thiol was a phytochelatin with two
      subunits (PC(2)). Compared to the classical methods for purification of
      phytochelatins, this new method is more specific, simple, and rapid and is
      suitable for purification of PCs in a large scale as well as sample preparation
      for mass spectrometry analysis.

PMID- 14670069
TI  - Partition coefficients of ionizable compounds in o-nitrophenyl octyl ether/water
      measured by the potentiometric method.
AB  - The objective of this study was to investigate the reliability of potentiometric
      measurements of partition coefficients (log P) in the o-NPOE/water system, o
      nitrophenyl octyl ether being an organic solvent widely used for the voltammetric
      determination of the partition coefficient of ions. Three sets of ionizable model
      compounds were explored in this study. The results showed that the potentiometric
      technique gave precise and reliable log P(npoe) values in the explored range of
      0.1-4.3.

PMID- 14670070
TI  - The 5-V window of polarizability of fluorinated diamond electrodes in aqueous
      solutions.
AB  - Heavily doped diamond films are quite actively studied for their promising
      applications in industrial as well as in fundamental electrochemistry (both for
      physicochemical studies and in the field of electroanalysis), because of their
      very high stability toward chemical and electrochemical oxidative attacks.
      Fluorinated diamond electrodes exhibit an exceptionally lower electrocatalytic
      activity toward reactions involving adsorbed intermediates, as a result of the F
      termination of the surface dangling bonds. This feature allows the investigation
      of the widest range of potentials for an electrode material in aqueous solution,
      being limited only by the formation of free hydrogen [E degrees (H*/H2) = -2.3
      V(SHE)] and hydroxyl [E degrees (*OH,H+/H2O) = 2.74 V(SHE)] radicals, at the two
      boundaries of the approximately 5-V polarization window.

PMID- 14670072
TI  - Non-protein bound iron release during chemotherapy in cancer patients.
AB  - Non-protein bound iron (NPBI) is able to catalyse oxidative reactions, causing
      damage to vital structures. Adverse effects induced by cisplatin seem, in part,
      to be mediated by free radicals. In the present study, we have measured plasma
      NPBI, various other iron parameters and antioxidants in 28 cancer patients
      undergoing cisplatin-based chemotherapy at various time points before and during
      chemotherapy. No NPBI was present prior to therapy, but within 1-4 days following
      the first administration of chemotherapy, mean NPBI rose significantly to 10.6+/
      6.6 micromol/l (range, 0.6-21.3 micromol/l) in 18 (64.3%) of the 28 patients
      measured. The rise in NPBI was accompanied by a significant rise in total plasma
      iron and ferritin and a marked decrease in the latent iron-binding capacity.
      Concomitantly, plasma vitamins C and E decreased significantly, indicating
      consumption of antioxidants. Similar observations were also made during the
      fourth chemotherapy cycle. The increase in NPBI preceded and correlated
      significantly with chemotherapy toxicity, such as a decrease in leucocyte count
      and haemoglobin, with a transient rise in various liver enzymes and with known
      cisplatin-related toxicity, i.e. the loss of renal and hearing function. In
      conclusion, cisplatin chemotherapy induces oxidative damage which rapidly leads
      to release of iron from intracellular proteins and the appearance of NPBI. Bone
      marrow, red blood cells, liver and kidney seem to be a likely source of NPBI. The
      observed high levels of NPBI may be a major causative determinant in chemotherapy
      induced toxicity.

PMID- 14670073
TI  - Non-invasive evaluation of left ventricular filling pressures in patients with
      abnormal relaxation.
AB  - The aim of the present study was to assess the ability of several
      echocardiographic and TDI (tissue Doppler imaging) parameters to predict an
      elevated LVEDP (left ventricular end-diastolic pressure) in patients with
      abnormal relaxation. Eighty-two consecutive patients presenting with an E /A
      ratio (ratio of early-to-late diastolic peak transmitral velocity) <0.9 scheduled
      for left heart catheterization underwent echocardiography, including TDI, and
      measurement of LVEDP using fluid-filled catheters. The difference in duration
      between P V (R) (retrograde peak in the pulmonary veins) and A (DeltaP V (R)- A )
      was calculated from pulsed Doppler recordings. V (P) (propagation velocity of the
      early mitral inflow) was determined by colour M-mode. TDI measurements included E
      ' (early diastolic peak myocardial velocities near the lateral mitral annulus),
      MVG (the early diastolic transmyocardial velocity gradient of the posterior basal
      wall) and the PRT (peak relaxation time), determined as the time interval between
      aortic valve closure and peak E '. Fifty-six patients presented with LVEDP values
      <15 mmHg, whereas an LVEDP >15 mmHg was found in 26 patients. The index DeltaP V
      (R)- A showed a significant linear correlation with LVEDP ( r =0.7, P <0.001) and
      provided the highest predictive accuracy for the identification of LVEDP >15 mmHg
      [AUC (area under receiver operating characteristic curve)=0.83], followed by PRT
      (AUC=0.67), whereas other TDI-derived parameters failed to reach significance. In
      conclusion, DeltaP V (R)- A enabled the most accurate non-invasive estimation of
      LVEDP. A prolonged peak relaxation time was the only TDI-derived index that
      differed significantly between patient groups.

PMID- 14670074
TI  - Dopamine in the ink defence system of Sepia officinalis: biosynthesis, vesicular
      compartmentation in mature ink gland cells, nitric oxide (NO)/cGMP-induced
      depletion and fate in secreted ink.
AB  - The biosynthesis, localization and fate of catecholamines in the ink gland of the
      cuttlefish Sepia officinalis were investigated by combined biochemical and
      immunohistocytochemical methodologies. HPLC analysis of crude ink gland extracts
      indicated the presence of dopa (2.18+/-0.82 nmol/mg of protein) and DA (dopamine,
      0.06+/-0.02 nmol/mg of protein), but no detectable noradrenaline or adrenaline.
      DA was shown to derive from L-tyrosine, according to experiments performed by
      incubating intact ink glands with [L-14C]tyrosine. The biosynthetic process
      involves a tyrosine hydroxylase and a dopa decarboxylase pathway and is
      independent of tyrosinase. The tyrosine hydroxylase activity was detected under
      conditions of tyrosinase suppression in the cytosolic fraction, but not in the
      melanosomal fraction, of ink gland extracts, and the presence of the enzyme was
      confirmed by Western-blot analysis. Dopa and DA were found to be released from
      the ink glands by processes controlled through the NMDA-nitric oxide-cGMP (where
      NMDA stands for N -methyl-D-aspartate) signalling pathway, as apparent from
      incubation experiments performed with [L-14C]tyrosine in the presence of NMDA,
      diethylamine NONOate (diethylamine diazeniumdiolate), a nitric oxide donor, 8
      bromo-cGMP or a guanylyl cyclase inhibitor. Immunohistochemical results coupled
      with electron microscopy indicated that DA was concentrated in vesicles
      specifically localized in the mature melanin-producing cells of the ink gland
      proximal to the lumen and separated from the melanin-containing melanosomes. NMDA
      receptor stimulation or exposure to an NO donor caused a marked loss of DA
      immunoreactivity in mature cells, consistent with a release process. In the lumen
      of the ink gland, where mature exhausted cells pour their contents, DA
      immunoreactivity was found to be associated with the melanin granules, due
      apparently to physical adsorption. Overall, these results point to DA as a marker
      of cell maturation in Sepia ink gland subject to release by the NO/cGMP
      signalling pathway, and disclose apparently overlooked DA-melanin interactions in
      secreted ink of possible relevance to the defence mechanism.

PMID- 14670075
TI  - TAB3, a new binding partner of the protein kinase TAK1.
AB  - We have identified a new binding partner of the TGFbeta (transforming growth
      factor-beta)-activated protein kinase (TAK1), termed TAB3 (TAK1-binding protein
      3), which shares 48% amino acid sequence identity with TAB2. Our results indicate
      that two distinct TAK1 complexes are present in cells. One comprises TAK1
      complexed with TAB1 and TAB2, and the other TAK1 complexed with TAB1 and TAB3.
      Both complexes are activated in response to tumour necrosis factor-alpha or
      interleukin-1 in human epithelial KB cells or bacterial lipopolysaccharide in
      RAW264.7 macrophages, and are subject to feedback control by stress-activated
      protein kinase 2a (SAPK2a; also called p38alpha). The electrophoretic mobility of
      TAB2 and TAB3 decreases in response to these agonists or osmotic shock, and is
      reversed by treatment with protein phosphatase-1. The decrease in mobility of
      TAB3 is prevented if the cells are incubated with SB 203580 before stimulation,
      but treatment with SB 203580 produces forms of TAB2 with a mobility intermediate
      between that observed for TAB2 in unstimulated and stimulated cells. Similar
      results were obtained in embryonic fibroblasts from mice deficient in
      SAPK2a/p38alpha. Our results indicate that TAB3 is phosphorylated via the
      SAPK2a/p38alpha pathway, whereas TAB2 is phosphorylated at two or more sites by
      both an SAPK2a/p38alpha-dependent and an SB 203580-independent kinase. The
      SAPK2a/p38alpha-mediated phosphorylation of TAB2 and TAB3 may contribute to the
      SAPK2a/p38alpha-mediated feedback control of TAK1 activity that also involves the
      phosphorylation of TAB1. We also show that the agonist-induced activation of TAK1
      complexes requires the phosphorylation of the TAK1 catalytic subunit at a
      serine/threonine residue(s).

PMID- 14670076
TI  - Syndecan-4 regulates localization, activity and stability of protein kinase C
      alpha.
AB  - During cell-matrix adhesion, syndecan-4 transmembrane heparan sulphate
      proteoglycan plays a critical role in the formation of focal adhesions and stress
      fibres. We have shown previously that the syndecan-4 cytoplasmic domain directly
      binds to and activates PKC-alpha (protein kinase C-alpha) in vitro [Oh, Woods and
      Couchman (1997) J. Biol. Chem. 272, 8133-8136]. However, whether syndecan-4 has
      the same activity in vivo needs to be addressed. Using mammalian two-hybrid
      assays, we showed that syndecan-4 interacted with PKC-alpha in vivo and that this
      interaction was mediated through syndecan-4 cytoplasmic domain. Furthermore, the
      activation of PKC increased the extent of interaction between syndecan-4 and PKC
      alpha. Overexpression of syndecan-4, but not a mutant lacking its cytoplasmic
      domain, specifically increased the level of endogenous PKC-alpha and enhanced the
      translocation of PKC-alpha into both detergent-insoluble and membrane fractions.
      In addition, rat embryo fibroblasts overexpressing syndecan-4 exhibited a slowed
      down-regulation of PKC-alpha in response either to a prolonged treatment with PMA
      or to maintaining cells in suspension culture. PKC-alpha immunocomplex kinase
      assays also showed that syndecan-4 overexpression increased the activity of
      membrane PKC-alpha. Taken together, these results suggest that syndecan-4
      interacts with PKC-alpha in vivo and regulates its localization, activity and
      stability.

PMID- 14670078
TI  - A synergistic relationship between three regions of stathmin family proteins is
      required for the formation of a stable complex with tubulin.
AB  - Stathmin is a ubiquitous 17 kDa cytosolic phosphoprotein proposed to play a
      general role in the integration and relay of intracellular signalling pathways.
      It is believed to regulate microtubule dynamics by sequestering tubulin in a
      complex made of two tubulin heterodimers per stathmin molecule (T2S complex). The
      other proteins of the stathmin family can also bind two tubulin heterodimers
      through their SLD (stathmin-like domain), but the different tubulin:SLD complexes
      display varying stabilities. In this study, we analysed the relative influence of
      three regions of SLDs on the interaction with tubulin and the mechanistic
      processes that lead to its sequestration. Tubulin-binding properties of fragments
      and chimaeras of stathmin and RB3(SLD) were studied in vitro by tubulin
      polymerization, size-exclusion chromatography and surface plasmon resonance
      assays. Our results show that the N-terminal region of SLDs favours the binding
      of the first tubulin heterodimer and that the second C-terminal tubulinbinding
      site confers the specific stability of a given tubulin:SLD complex. Our results
      highlight the molecular processes by which tubulin co-operatively interacts with
      the SLDs. This knowledge may contribute to drug development aimed at disturbing
      microtubules that could be used for the treatment of cancer.

PMID- 14670077
TI  - Induced oxidative stress and activated expression of manganese superoxide
      dismutase during hepatitis C virus replication: role of JNK, p38 MAPK and AP-1.
AB  - Activation of cellular kinases and transcription factors mediates the early phase
      of the cellular response to chemically or biologically induced stress. In the
      present study we investigated the oxidant/antioxidant balance in Huh-7 cells
      expressing the HCV (hepatitis C virus) subgenomic replicon, and observed a 5-fold
      increase in oxidative stress during HCV replication. We used MnSOD (manganese
      superoxide dismutase) as an indicator of the cellular antioxidant response, and
      found that its activity, protein levels and promoter activity were significantly
      increased, whereas Cu/ZnSOD was not affected. The oxidative stress-induced
      protein kinases p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun N
      terminal kinase) were activated in the HCV repliconcontaining cells and in Huh-7
      cells transduced with Ad-NS5A [a recombinant adenovirus encoding NS5A (non
      structural protein 5A)], coupled with a 4-5-fold increase in AP-1 (activator
      protein-1) DNA binding. Ava.1 cells, which encode a replication-defective HCV
      replicon, showed no significant changes in MnSOD, p38 MAPK or JNK activity. The
      AP-1 inhibitors dithiothreitol and N -acetylcysteine, as well as a dominant
      negative AP-1 mutant, significantly reduced AP-1 activation, demonstrating that
      this activation is oxidative stress-related. Exogenous NS5A had no effect on AP-1
      activation in vitro, suggesting that NS5A acts at the upstream targets of AP-1
      involving p38 MAPK and JNK signalling cascades. AP-1-dependent gene expression
      was increased in HCV subgenomic replicon-expressing Huh-7 cells. MnSOD activation
      was blocked by inhibitors of JNK (JNKI1) and p38 MAPK (SB203580), but not by an
      ERK (extracellular-signal-regulated kinase) inhibitor (U0126), in HCV-replicating
      and Ad-NS5A-transduced cells. Our results demonstrate that cellular responses to
      oxidative stress in HCV subgenomic replicon-expressing and Ad-NS5A-transduced
      cells are regulated by two distinct signalling pathways involving p38 MAPK and
      JNK via AP-1 that is linked to increased oxidative stress and therefore to an
      increased antioxidant MnSOD response.

PMID- 14670079
TI  - Phosphorylation regulates nucleophosmin targeting to the centrosome during
      mitosis as detected by cross-reactive phosphorylation-specific MKK1/MKK2
      antibodies.
AB  - Phosphorylation-specific antibodies provide a powerful tool for analysing the
      regulation and activity of proteins in the MAP (mitogen-activated protein) kinase
      and other signalling pathways. Using synchronized cells, it was observed that
      phosphorylation-specific antibodies developed against the active form of
      MKK1/MKK2 (MAP kinase kinase-1 and -2) reacted with a protein that was approx. 35
      kDa during G2/M-phase of the cell cycle. Failure of the 35 kDa protein to react
      with phosphorylation-independent MKK1/MKK2 antibodies suggested that this protein
      was not related to MKK1 or MKK2. Thus the 35 kDa protein was isolated by
      immunoprecipitation with the phospho-MKK1/MKK2 antibody and identified by MS.
      Peptide sequence analysis revealed matches with NPM (nucleophosmin/B23), a
      phosphoprotein involved in nucleolar assembly, centrosome duplication and
      ribosome assembly and transport. Biochemical and immunocytochemistry analyses
      verified that the phospho-MKK1/MKK2 antibodies cross-reacted with NPM that was
      phosphorylated at Thr234 and Thr237 during G2/M-phase, which are the same sites
      that are targeted by Cdc2 (cell division cycle protein-2) during mitosis. Using
      phosphorylation site mutants, we show that phosphorylation of Thr234 and Thr237
      is required for NPM immunoreactivity with the phospho-MKK1/MKK2 antibody.
      Moreover, phosphorylation of Thr234 and Thr237 was demonstrated to regulate NPM
      localization to the centrosome after nuclear envelope breakdown in mitotic cells.
      These findings reveal a new insight into the role of phosphorylation in
      regulating NPM targeting during mitosis. However, caution should be used when
      using commercially available phospho-MKK1/MKK2 antibodies to examine the
      regulation of MKK1/MKK2 during mitotic transitions, owing to their cross
      reactivity with phosphorylated NPM at this time of the cell cycle.

PMID- 14670080
TI  - Phosphoinositides differentially regulate alpha-actinin flexibility and function.
AB  - Alpha-actinin is a cell-adhesion and cytoskeletal protein that bundles actin
      microfilaments and links these filaments directly to integrin-adhesion receptors.
      Phosphoinositides bind to and regulate the interaction of a-actinin with actin
      filaments and integrin receptors. In the present study, we demonstrate that
      PtdIns(3,4,5)P3 inhibits and disrupts a-actinin-bundling activity, whereas
      PtdIns(4,5)P2 can only inhibit activity. In addition, a protease-sensitivity
      assay was developed to examine the flexibility of the linker region between the
      actin-binding domain and the spectrin repeats of a-actinin. Both
      phosphoinositides influenced the extent of proteolysis and the cleavage sites.
      PtdIns(4,5)P2 binding decreased the proteolysis of a-actinin, suggesting a role
      in stabilizing the structure of the protein. In contrast, PtdIns(3,4,5)P3 binding
      enhanced a-actinin proteolysis, indicating an increase in the flexibility of the
      protein. Furthermore, phosphoinositide binding influenced the proteolysis of the
      N- and C-terminal domains of a-actinin, indicating regulation of structure within
      both domains. These results support the hypothesis that PtdIns(4,5)P2 and
      PtdIns(3,4,5)P3 differentially regulate a-actinin function by modulating the
      structure and flexibility of the protein.

PMID- 14670081
TI  - Relocalized redox-active lysosomal iron is an important mediator of oxidative
      stress-induced DNA damage.
AB  - Oxidative damage to nuclear DNA is known to involve site-specific Fenton-type
      chemistry catalysed by redox-active iron or copper in the immediate vicinity of
      DNA. However, the presence of transition metals in the nucleus has not been shown
      convincingly. Recently, it was proposed that a major part of the cellular pool of
      loose iron is confined within the acidic vacuolar compartment [Yu, Persson, Eaton
      and Brunk (2003) Free Radical Biol. Med. 34, 1243-1252; Persson, Yu, Tirosh,
      Eaton and Brunk (2003) Free Radical Biol. Med. 34, 1295-1305]. Consequently,
      rupture of secondary lysosomes, as well as subsequent relocation of labile iron
      to the nucleus, could be an important intermediary step in the generation of
      oxidative damage to DNA. To test this concept we employed the potent iron
      chelator DFO (desferrioxamine) conjugated with starch to form an HMM-DFO (high
      molecular-mass DFO complex). The HMM-DFO complex will enter cells only via fluid
      phase endocytosis and remain within the acidic vacuolar compartment, thereby
      chelating redox-active iron exclusively inside the endosomal/lysosomal
      compartment. Both free DFO and HMM-DFO equally protected lysosomal-membrane
      integrity against H2O2-induced oxidative disruption. More importantly, both forms
      of DFO prevented H2O2-induced strand breaks in nuclear DNA, including telomeres.
      To exclude the possibility that lysosomal hydrolases, rather than iron, caused
      the observed DNA damage, limited lysosomal rupture was induced using the
      lysosomotropic detergent O-methyl-serine dodecylamine hydrochloride;
      subsequently, hardly any DNA damage was found. These observations suggest that
      rapid oxidative damage to cellular DNA is minimal in the absence of redox-active
      iron and that oxidant-mediated DNA damage, observed in normal cells, is mainly
      derived from intralysosomal iron translocated to the nucleus after lysosomal
      rupture.

PMID- 14670082
TI  - Mutations in and near the second calcium-binding domain of integrin alphaIIb
      affect the structure and function of integrin alphaIIbbeta3.
AB  - Calcium-binding domains in the alpha-subunit of integrins contain a central loop
      structure. To examine the importance of the loop structure, a series of alphaIIb
      mutants containing changes to the calcium-liganding amino acids have been
      constructed. Significantly, none of the mutant alphaIIbbeta3 complexes was
      detected on the surface of transfected cells, but mutant pro-alphaIIb was
      detected in cell lysates in complex with beta3. To study the importance of the
      regions flanking the second calcium-binding domain for ligand-binding and ligand
      binding specificity, three alphaIIb/alpha5 chimaeras containing alpha5 sequences
      flanking or flanking and including the second calcium-binding domain were
      constructed. The chimaera containing both alpha5-flanking regions was not
      expressed on the cell surface, but FR1 and FR2, substituting either the first or
      second flanking region, were expressed. FR1beta3-transfected cells lost the
      ability to adhere to fibrinogen and to support aggregation and had minimal
      fibrinogen-binding ability. The heterodimer complex was less stable than the wild
      type. FR2beta3-transfected cells adhered to fibrinogen and bound soluble
      fibrinogen with higher affinity when compared with wild-type. In addition, the
      heterodimer complex was more stable than wild-type. These results indicate that
      the conformation of the second calcium-binding domain is critical for maturation
      of the alphaIIbbeta3 complex and expression on the cell surface and that the
      surrounding sequences are critical for alphaIIbbeta3 function.

PMID- 14670084
TI  - Bubble-induced detachment of affinity-adsorbed erythrocytes.
AB  - It is desirable that cells adsorbed in affinity-separation processes be easily
      recovered from the adsorption surface, without excessive dilution, once
      contaminants have been removed. The present study investigates the use of gas
      bubble-induced shear stress for the recovery of affinity-adsorbed human
      erythrocytes. This method has previously been demonstrated to be effective with
      yeast cells, where it allows cells to be attached, washed and detached under
      isocratic conditions. Concanavalin A (Con A), used as the binding agent, was
      attached to the inside of nylon tubes. Whole blood solution, diluted to an
      erythrocyte concentration of 1x10(8) x ml(-1) with PBS, was incubated with the
      Con A-nylon surface and then washed with PBS prior to elution. To effect elution,
      air bubbles of known volume were introduced to the buffer feed to the tubes and
      the effects of bubble size, bubble volume and bubble velocity on detachment being
      determined. The results obtained showed that the most significant parameter was
      bubble number, with up to 90% of attached cells being recovered using a five
      bubble sequence. Microscopic examination showed no evidence of mechanical damage
      to the detached cells.

PMID- 14670085
TI  - TbAGO1, an argonaute protein required for RNA interference, is involved in
      mitosis and chromosome segregation in Trypanosoma brucei.
AB  - BACKGROUND: RNA silencing processes are widespread in almost all eukaryotic
      organisms. They have various functions including genome protection, and the
      control of gene expression, development and heterochromatin formation. RNA
      interference (RNAi) is the post-transcriptional destruction of RNA, which is
      mediated by a ribonucleoprotein complex that contains, among several components,
      RNA helicases and Argonaute proteins. RNAi is functional in trypanosomes,
      protozoan parasites that separated very early from the main eukaryotic lineage
      and exhibit several intriguing features in terms of the control of gene
      expression. In this report, we investigated the functions of RNAi in Trypanosoma
      brucei. RESULTS: By searching through genome databases, novel Argonaute-like
      proteins were identified in several protozoa that belong to the kinetoplastid
      order, a group of organisms that diverged early from the main eukaryotic lineage.
      T. brucei possesses two Argonaute-like genes termed TbAGO1 and TbPWI1. Dual
      transient transfection assays suggest that TbAGO1, but not TbPWI1, is involved in
      RNAi. The entire coding region of TbAGO1 was deleted by double gene knockout.
      TbAGO1-/- cells turned out to be completely resistant to RNAi generated either by
      transfected double-stranded RNA or by expression of an inverted repeat. TbAGO1-/-
      cells were viable but showed a dramatically reduced growth rate. This was
      probably due to defects in mitosis and abnormal chromosome segregation as
      revealed by in situ analysis. The RNAi and growth phenotypes were complemented by
      the inducible expression of a GFP::TbAGO1 fusion protein that revealed the
      cytoplasmic location of the protein. CONCLUSIONS: The requirement of TbAGO1 for
      RNAi in trypanosomes demonstrates the evolutionary ancient involvement of
      Argonaute proteins in RNAi silencing processes. RNAi-deficient TbAGO1-/- cells
      showed numerous defects in chromosome segregation and mitotic spindle assembly.
      We propose a working hypothesis in which RNAi would be involved in
      heterochromatin formation at the centromere and therefore in chromosome
      segregation.

PMID- 14670086
TI  - The peroxisome proliferator activated receptor delta is required for the
      differentiation of THP-1 monocytic cells by phorbol ester.
AB  - BACKGROUND: PPARdelta (NR1C2) promotes lipid accumulation in human macrophages in
      vitro and has been implicated in the response of macrophages to vLDL. We have
      investigated the role of PPARdelta in PMA-stimulated macrophage differentiation.
      The THP-1 monocytic cell line which displays macrophage like differentiation in
      response to phorbol esters was used as a model system. We manipulated the
      response to PMA using a potent synthetic agonist of PPARdelta , compound F. THP-1
      sub-lines that either over-expressed PPARdelta protein, or expressed PPARdelta
      anti-sense RNA were generated. We then explored the effects of these genetic
      modulations on the differentiation process. RESULTS: The PPARdelta agonist,
      compound F, stimulated differentiation in the presence of sub-nanomolar
      concentrations of phorbol ester. Several markers of differentiation were induced
      by compound F in a synergistic fashion with phorbol ester, including CD68 and
      IL8. Over-expression of PPARdelta also sensitised THP-1 cells to phorbol ester
      and correspondingly, inhibition of PPARdelta by anti-sense RNA completely
      abolished this response. CONCLUSIONS: These data collectively demonstrate that
      PPARdelta plays a fundamental role in mediating a subset of cellular effects of
      phorbol ester and supports observations from mouse knockout models that PPARdelta
      is involved in macrophage-mediated inflammatory responses.

PMID- 14670087
TI  - The role of the carotenoids, lutein and zeaxanthin, in protecting against age
      related macular degeneration: a review based on controversial evidence.
AB  - PURPOSE: A review of the role of the carotenoids, lutein and zeaxanthin, and
      their function in altering the pathogenesis of age-related macular degeneration
      (AMD). METHODS: Medline and Embase search. RESULTS: Recent evidence introduces
      the possibility that lutein and zeaxanthin, carotenoids found in a variety of
      fruits and vegetables may protect against the common eye disease of macular
      degeneration. This potential and the lack to slow the progression of macular
      degeneration, has fueled high public interest in the health benefits of these
      carotenoids and prompted their inclusion in various supplements. The body of
      evidence supporting a role in this disease ranges from basic studies in
      experimental animals to various other clinical and epidemiological studies.
      Whilst some epidemiological studies suggest a beneficial role for carotenoids in
      the prevention of AMD, others are found to be unrelated to it. Results of some
      clinical studies indicate that the risk for AMD is reduced when levels of the
      carotenoids are elevated in the serum or diet, but this correlation is not
      observed in other studies. Published data concerning the toxicity of the
      carotenoids or the optimum dosage of these supplements is lacking. CONCLUSION: An
      intake of dietary supplied nutrients rich in the carotenoids, lutein and
      zeaxanthin, appears to be beneficial in protecting retinal tissues, but this is
      not proven. Until scientifically sound knowledge is available we recommend for
      patients judged to be at risk for AMD to: alter their diet to more dark green
      leafy vegetables, wear UV protective lenses and a hat when outdoors. Future
      investigations on the role of nutrition, light exposure, genetics, and
      combinations of photodynamic therapy with intravitreal steroid (triamcinolone
      acetonide) injections hold potential for future treatment possibilities.

PMID- 14670088
TI  - Age-related differences in 1p and 19q deletions in oligodendrogliomas.
AB  - BACKGROUND: Recent reports indicate that anaplastic oligodendrogliomas frequently
      show allelic losses on chromosome arms 1p and 19q, and that these deletions are
      associated with better chemotherapeutic response and overall patient survival.
      Because of the diversified genetic makeup of the population and the centralized
      provincial referral system for brain tumor patients in Manitoba, the
      epidemiological features of such tumors sometimes differ from the published data
      acquired from non-community based settings. In this study, we assessed the
      prevalence of allelic deletions for chromosome arms 1p and 19q in anaplastic and
      in low-grade oligodendrogliomas in the Manitoba population. METHODS: Loss of
      heterozygosity (LOH) analysis of brain tumors was carried out using 4
      microsatellite markers (D1S508, D1S2734, D19S219 and D19S412) and a PCR based
      assay. The tumors were consecutively acquired during the period September 1999
      March 2001 and a total of 63 tumors were assessed. RESULTS: We found that allelic
      loss of chromosome 1p and 19q was higher in oligodendrogliomas than in other
      diffuse gliomas and that for anaplastic oligodendrogliomas, younger patients
      exhibited significantly more deletions than older patients (>60 years of age).
      CONCLUSIONS: These studies suggest that age may be a factor in the genetic
      alterations of oligodendrogliomas. In addition, these studies demonstrate that
      this assay can easily be carried out in a cost-effective manner in a small
      tertiary center.

PMID- 14670089
TI  - Evaluation of five different cDNA labeling methods for microarrays using spike
      controls.
AB  - BACKGROUND: Several different cDNA labeling methods have been developed for
      microarray based gene expression analysis. We have examined the accuracy and
      reproducibility of such five commercially available methods in detection of
      predetermined ratio values from target spike mRNAs (A. thaliana) in a background
      of total RNA. The five different labeling methods were: direct labeling
      (CyScribe), indirect labeling (FairPlay--aminoallyl), two protocols with
      dendrimer technology (3DNA Array 50 and 3DNA submicro), and hapten-antibody
      enzymatic labeling (Micromax TSA). Ten spike controls were mixed to give expected
      Cy5/Cy3 ratios in the range 0.125 to 6.0. The amounts of total RNA used in the
      labeling reactions ranged from 5-50 microg. RESULTS: The 3DNA array 50 and
      CyScribe labeling methods performed best with respect to relative deviation from
      the expected values (16% and 17% respectively). These two methods also displayed
      the best overall accuracy and reproducibility. The FairPlay method had the lowest
      total experimental variation (22%), but the estimated values were consistently
      higher than the expected values (36%). TSA had both the largest experimental
      variation and the largest deviation from the expected values (45% and 48%
      respectively). CONCLUSION: We demonstrate the usefulness of spike controls in
      validation and comparison of cDNA labeling methods for microarray experiments.

PMID- 14670090
TI  - Comparison of Technetium-99m-MIBI imaging with MRI for detection of spine
      involvement in patients with multiple myeloma.
AB  - BACKGROUND: Recently, radiopharmaceutical scanning with Tc-99m-MIBI was reported
      to depict areas with active bone disease in multiple myeloma (MM) with both high
      sensitivity and specificity. This observation was explained by the uptake of Tc
      99m-MIBI by neoplastic cells. The present investigation evaluates whether Tc-99m
      MIBI imaging and magnetic resonance imaging (MRI) perform equally well in
      detecting myelomatous bone marrow lesions. METHODS: In 21 patients with MM, MRIs
      of the vertebral region TH12 to S1 and whole body scans with Tc-99m-MIBI were
      done. RESULTS: Tc-99m-MIBI scanning missed bone marrow infiltration in 43 of 87
      vertebrae (50.5%) in which MRI showed neoplastic bone marrow involvement. In
      patients with disease stage I+II, Tc-99m-MIBI scanning was negative in all of 24
      vertebrae infiltrated according to MRI. In patients with disease stage III, Tc
      99m-MIBI scanning detected 44 of 63 (70%) vertebrae involved by neoplastic
      disease. CONCLUSION: Tc-99m-MIBI scanning underestimated the extent of
      myelomatous bone marrow infiltration in the spine, especially in patients with
      low disease stage.

PMID- 14670091
TI  - Multicentric Castleman's disease and Kaposi's sarcoma in a cyclosporin treated,
      HIV-1 negative patient: case report.
AB  - BACKGROUND: Multicentric Castleman's disease (MCD) is a rare disease, but is more
      frequent in AIDS patients. MCD has only been reported twice before in patients
      receiving immunosuppressive therapy after renal transplantation, and never in
      patients receiving immunosuppressive therapy without transplantation. About half
      of the cases of MCD are human herpesvirus 8 (HHV8) - related, in contrast to
      Kaposi's sarcoma, a more common complication arising after immunosuppression,
      where the virus is found in virtually all cases. CASE PRESENTATION: We report a
      HIV-1 negative, non-transplant patient who developed HHV8-associated multicentric
      Castleman's disease and Kaposi's sarcoma after 17 years of immunosuppressive
      treatment with cyclosporin A for a minimal change nephropathy. Chemotherapy with
      liposomal doxorubicin resolved both symptoms of multicentric Castleman's disease
      and Kaposi's sarcoma in this patient. A concomitant decline in the HHV8 viral
      load in serum/plasma, as determined by a quantitative real-time PCR assay, was
      observed. CONCLUSIONS: Multicentric Castleman's disease can be a complication of
      cyclosporin A treatment. Both multicentric Castleman's disease and Kaposi's
      sarcoma in this patient were responsive to liposomal doxorubicin, the treatment
      of choice for Kaposi's sarcoma at the moment, again suggesting a common mechanism
      linking both disorders, at least for HHV8-positive multicentric Castleman's
      disease and Kaposi's sarcoma.HHV8 viral load measurements can be used to monitor
      effectiveness of therapy.

PMID- 14670092
TI  - A framework for power analysis using a structural equation modelling procedure.
AB  - BACKGROUND: This paper demonstrates how structural equation modelling (SEM) can
      be used as a tool to aid in carrying out power analyses. For many complex
      multivariate designs that are increasingly being employed, power analyses can be
      difficult to carry out, because the software available lacks sufficient
      flexibility. Satorra and Saris developed a method for estimating the power of the
      likelihood ratio test for structural equation models. Whilst the Satorra and
      Saris approach is familiar to researchers who use the structural equation
      modelling approach, it is less well known amongst other researchers. The SEM
      approach can be equivalent to other multivariate statistical tests, and therefore
      the Satorra and Saris approach to power analysis can be used. METHODS: The
      covariance matrix, along with a vector of means, relating to the alternative
      hypothesis is generated. This represents the hypothesised population effects. A
      model (representing the null hypothesis) is then tested in a structural equation
      model, using the population parameters as input. An analysis based on the chi
      square of this model can provide estimates of the sample size required for
      different levels of power to reject the null hypothesis. CONCLUSIONS: The SEM
      based power analysis approach may prove useful for researchers designing research
      in the health and medical spheres.

PMID- 14670093
TI  - Relationship between apolipoprotein(a) size polymorphism and coronary heart
      disease in overweight subjects.
AB  - BACKGROUND: Overweight is associated with an increased cardiovascular risk which
      is only partially explained by conventional risk factors. The objective of this
      study was to evaluate lipoprotein(a) [Lp(a)] plasma levels and apolipoprotein(a)
      [apo(a)] phenotypes in relation to coronary heart disease (CHD) in overweight
      subjects. METHODS: A total of 275 overweight (BMI > or = 27 kg/m2) subjects, of
      which 155 had experienced a CHD event, 337 normal weight subjects with prior CHD
      and 103 CHD-free normal weight subjects were enrolled in the study. Lp(a) levels
      were determined by an ELISA technique and apo(a) isoforms were detected by a high
      resolution immunoblotting method. RESULTS: Lp(a) levels were similar in the three
      study groups. Overweight subjects with CHD had Lp(a) concentrations significantly
      higher than those without [median (interquartile range): 20 (5-50.3) versus 12.6
      (2.6-38.6) mg/dl, P < 0.05]. Furthermore, overweight subjects with CHD showed a
      higher prevalence of low molecular weight apo(a) isoforms than those without
      (55.5% versus 40.8%, P < 0.05) and with respect to the control group (55.5%
      versus 39.8%, P < 0.05). Stepwise regression analysis showed that apo(a)
      phenotypes, but not Lp(a) levels, entered the model as significant independent
      predictors of CHD in overweight subjects. CONCLUSIONS: Our data indicate that
      small-sized apo(a) isoforms are associated with CHD in overweight subjects. The
      characterization of apo(a) phenotypes might serve as a reliable biomarker to
      better assess the overall CHD risk of each subject with elevated BMI, leading to
      more intensive treatment of modifiable cardiovascular risk factors.

PMID- 14670094
TI  - Automated measurement of Drosophila wings.
AB  - BACKGROUND: Many studies in evolutionary biology and genetics are limited by the
      rate at which phenotypic information can be acquired. The wings of Drosophila
      species are a favorable target for automated analysis because of the many
      interesting questions in evolution and development that can be addressed with
      them, and because of their simple structure. RESULTS: We have developed an
      automated image analysis system (WINGMACHINE) that measures the positions of all
      the veins and the edges of the wing blade of Drosophilid flies. A video image is
      obtained with the aid of a simple suction device that immobilizes the wing of a
      live fly. Low-level processing is used to find the major intersections of the
      veins. High-level processing then optimizes the fit of an a priori B-spline model
      of wing shape. WINGMACHINE allows the measurement of 1 wing per minute, including
      handling, imaging, analysis, and data editing. The repeatabilities of 12 vein
      intersections averaged 86% in a sample of flies of the same species and sex.
      Comparison of 2400 wings of 25 Drosophilid species shows that wing shape is quite
      conservative within the group, but that almost all taxa are diagnosably different
      from one another. Wing shape retains some phylogenetic structure, although some
      species have shapes very different from closely related species. The WINGMACHINE
      system facilitates artificial selection experiments on complex aspects of wing
      shape. We selected on an index which is a function of 14 separate measurements of
      each wing. After 14 generations, we achieved a 15 S.D. difference between up and
      down-selected treatments. CONCLUSION: WINGMACHINE enables rapid, highly
      repeatable measurements of wings in the family Drosophilidae. Our approach to
      image analysis may be applicable to a variety of biological objects that can be
      represented as a framework of connected lines.

PMID- 14670095
TI  - View from a small island.

PMID- 14670096
TI  - Motivation, characterization, and strategy for tissue engineering the
      temporomandibular joint disc.
AB  - The purpose of this review is to serve as the standard point of reference in
      guiding researchers investigating the tissue engineering of the temporomandibular
      joint (TMJ) disc. Tissue engineering of the TMJ disc is in its infancy, and
      currently there exists a gap between the tissue engineering community and the TMJ
      characterization community. The primary goal is to help bridge that gap by
      consolidating the characterization studies here as a reference to researchers
      attempting to tissue engineer the TMJ disc. A brief review of TMJ anatomy is
      provided, along with a description of relevant pathology, current treatment, and
      a rationale for engineering the TMJ disc. The biochemical composition and
      organization of the disc are reviewed, including glycosaminoglycan (GAG) and
      collagen content. The collagen of the disc is almost exclusively type I and
      primarily runs anteroposteriorly through the center and in a ringlike fashion
      around the periphery. The GAG content is approximately an order of magnitude less
      than that of hyaline cartilage, and although the distribution is not entirely
      clear, it seems as though chondroitin and dermatan sulfate are by far the primary
      GAGs. Cellular characterization and mechanical properties under compression,
      tension, and shear are reviewed as well. The cells of the disc are not
      chondrocytes, but rather resemble fibrocytes and fibrochondrocytes and may be of
      the same lineage. Mechanically, the disc is certainly anisotropic and
      nonhomogeneous. Finally, a review of efforts in tissue engineering and cell
      culture studies of the disc is provided and we close with a description of the
      direction we envision/propose for successful tissue engineering of the TMJ disc.

PMID- 14670097
TI  - Cryopreservation of collagen-based tissue equivalents. I. Effect of freezing in
      the absence of cryoprotective agents.
AB  - The effect of freezing on the viability and mechanical properties of tissue
      equivalents (TEs) was determined under a variety of cooling conditions, with the
      ultimate aim of optimizing the cryopreservation process. TEs (a class of
      bioartificial tissues) were prepared by incubating entrapped human foreskin
      fibroblasts in collagen gels for a period of 2 weeks. TEs were detached from the
      substrate and frozen in phosphate-buffered saline using a controlled rate freezer
      (CRF) at various cooling rates (0.5, 2, 5, 20, and 40 degrees C/min to -80 or 
      160 degrees C) or in a directional solidification stage (DSS) (5 degrees C/min to
      -80 degrees C) or slam frozen (>1000 degrees C/min). Viability of the fibroblasts
      in the TEs was assessed by ethidium homodimer and Hoechst assays immediately
      after thawing. Uniaxial tension experiments were also performed on an MTS (Eden
      Prairie, MN) Micro Bionix system to assess the postthaw mechanical properties of
      the frozen-thawed TEs. Cooling rates of either 2 or 5 degrees C/min using the CRF
      were optimal for preserving both immediate cell viability and mechanical
      properties of the TEs, postthaw. By 72 h postthaw, TEs frozen in the CRF at 5
      degrees C/min to -80 degrees C showed a slight decrease in cell viability, with a
      significant increase in tangent modulus and ultimate tensile stress suggesting a
      cell-mediated recovery mechanism. Both the postthaw mechanical properties and
      cell viability are adversely affected by freezing to the lower end temperature of
      -160 degrees C. Mechanical properties are adversely affected by freezing in the
      DSS.

PMID- 14670098
TI  - Fabrication and biocompatibility of collagen sponge reinforced with poly(glycolic
      acid) fiber.
AB  - This article describes an investigation of collagen sponge mechanically
      reinforced through the incorporation of poly(glycolic acid) (PGA) fiber. A
      collagen solution with PGA fiber homogeneously dispersed at collagen:PGA weight
      ratios of 1.5, 0.8, 0.4, and 0.2 was freeze-dried, followed by dehydrothermal
      cross-linking to obtain collagen sponges incorporating PGA fiber to various
      extents. By scanning electron microscopy observation, the collagen sponges
      exhibited isotropic and interconnected pore structures with an average size of
      180 microm, irrespective of PGA fiber incorporation. As expected, PGA fiber
      incorporation enabled the collagen sponges to significantly enhance their
      compression strength. In vitro cell culture studies revealed that the number of
      L929 fibroblasts initially attached was significantly greater for any collagen
      sponge incorporating PGA fiber than for collagen sponge. The shrinkage of sponge
      after cell seeding was suppressed by fiber incorporation. It is possible that
      shrinkage suppression results in the superior cell attachment of sponge
      incorporating PGA fiber. After subcutaneous implantation into the backs of mice,
      the residual volume of collagen sponge incorporating PGA fiber was significant
      compared with that of collagen sponge and increased with a decrease in the
      collagen:PGA ratio. The greater number of cells infiltrated and deeper
      infiltration were observed for collagen sponge incorporating PGA fiber implanted
      subcutaneously. We conclude that the incorporation of PGA fiber is a simple and
      promising way to reinforce collagen sponge without impairing biocompatibility.

PMID- 14670099
TI  - Silk fibroin-coated three-dimensional polyurethane scaffolds for tissue
      engineering: interactions with normal human fibroblasts.
AB  - Silk fibroin (SF)-based or -coated biomaterials hold structural and surface
      properties that render them suitable for biomedical applications. In this work,
      we investigated the behavior of four strains of normal human adult fibroblasts
      (HAFs) seeded onto polyurethane foam, uncoated (PUF) or SF coated (PUF/SF). HAF
      adhesion within 3 h to PUF/SF was 2-fold that of adhesion to PUF. After 30 days
      of incubation in vitro, 37% more HAFs had grown on PUF/SF than on PUF. Taking
      10(5) cells as a basis for comparisons, HAFs on PUF/SF exhibited initially higher
      glucose consumption rates, but persistently lower glutamine uptake rates than on
      PUF, whereas the rates of lactate and interleukin 6 release and of extracellular
      assembly of type I collagen fibers were alike on either substrate. Moreover, HAFs
      on both PUF/SF and PUF never secreted any ELISA-assayable amounts of interleukin
      1beta, tumor necrosis factor alpha, and transforming growth factor beta(1).
      Hence, PUF/SF scaffolds embody a novel class of biomaterials favoring the
      adhesion, proliferation, and performance of specific metabolic tasks by HAFs
      without eliciting any concurrent secretion of the chief proinflammatory
      cytokines.

PMID- 14670100
TI  - Development of a plasma-polymerized surface suitable for the transplantation of
      keratinocyte-melanocyte cocultures for patients with vitiligo.
AB  - The purpose of this study was to develop a convenient methodology for the
      coculture of autologous melanocytes and keratinocytes for grafting of patients
      with vitiligo. While grafting of pure melanocytes may achieve repigmentation, the
      inclusion of keratinocytes ensures rapid reepithelialization. Previously we have
      used confluent sheets of keratinocytes (with melanocytes present) to transfer
      cells. However, we found that as the keratinocyte density increased, melanocyte
      number and function were downregulated. Accordingly in this study we explored
      combinations of three culture surfaces and three media, seeking to achieve
      subconfluent culture of primary keratinocytes with a reasonable density of
      melanocytes, using cells immediately after isolation from skin. For this in vitro
      study, the surfaces studied were uncoated glass coverslips, and glass coverslips
      coated with collagen I or a nitrogen-containing plasma polymer. The results show
      that both the substrate surface and the medium composition influence the
      proliferation and survival of melanocytes. Keratinocytes and melanocytes could be
      successfully cocultured on a chemically defined plasma polymer substrate using a
      serum-free medium.

PMID- 14670101
TI  - System-engineered cartilage using poly(N-isopropylacrylamide)-grafted gelatin as
      in situ-formable scaffold: in vivo performance.
AB  - Our previous study showed that cartilaginous tissue can be engineered in vitro
      with articular chondrocytes and poly(N-isopropylacrylamide)-grafted gelatin. This
      short-term in vivo study for cartilage repair was performed to screen a candidate
      method for a long-term study. In our previous in vitro study, however, two
      potential problems with the tissue-engineered cartilage were identified: (1).
      leakage of the transplant due to temperature decline and (2). concave deformation
      of transplant due to compressive loading. To solve these problems, we
      investigated in this study the usefulness of suturing with two different covering
      materials (periosteum or collagen film) and preculturing an engineered tissue for
      2 weeks. PNIPAAm-gelatin-based engineered cartilage samples were evaluated at 5
      weeks after operation by gross and microscopic examination. Leakage occurred only
      in specimens without precultured tissue and with a collagen film. Minimal surface
      deformation occurred in all specimens with precultured tissue. The score on gross
      examination showed that transplants with precultured tissue acquired a higher
      score than did the others. Histological evaluation showed a minimal foreign-body
      response of PNIPAAm-gelatin in all specimens and higher maturity as a
      cartilaginous tissue in specimens with precultured tissue. These results indicate
      that transplantation with precultured tissue may be a suitable method for a long
      term in vivo study.

PMID- 14670102
TI  - Three-dimensional biocompatible ascorbic acid-containing scaffold for bone tissue
      engineering.
AB  - A biodegradable, biocompatible, ascorbic acid-containing three-dimensional
      polyurethane matrix was developed for bone tissue-engineering scaffolds. This
      matrix was synthesized with lysine-di-isocyanate (LDI), ascorbic acid (AA),
      glycerol, and polyethylene glycol (PEG). LDI-glycerol-PEG-AA prepolymer when
      reacted with water foamed with the liberation of CO(2) to provide a pliable,
      spongy urethane polymer with pore diameters of 100 to 500 microm. The LDI
      glycerol-PEG-AA matrix degraded in aqueous solution and yielded lysine, glycerol,
      PEG, and ascorbic acid as breakdown products. The degradation products did not
      significantly affect the solution pH. The LDI-glycerol-PEG-AA matrix can be
      fabricated into diverse scaffold dimensions and the physicochemical properties of
      the polymer network supported in vitro cell growth. Green fluorescent protein
      transgenic mouse bone marrow cells (GFP-MBMCs) attached to the polymer matrix and
      remained viable, and the cells became confluent cultures. Furthermore, ascorbic
      acid released from LDI-glycerol-PEG-AA matrix stimulated cell proliferation, type
      I collagen, and alkaline phosphatase synthesis in vitro. Cells grown on LDI
      glycerol-PEG-AA matrix did not differ phenotypically from cells grown on tissue
      culture polystyrene plates as assessed by cell growth, expression of mRNA for
      collagen type I, and transforming growth factor beta(1). These observations
      suggest that AA-containing polyurethane may be useful in bone tissue-engineering
      applications.

PMID- 14670103
TI  - Natural marine sponge fiber skeleton: a biomimetic scaffold for human
      osteoprogenitor cell attachment, growth, and differentiation.
AB  - Identification of suitable scaffolds onto which human stem cells can be seeded to
      generate functional three-dimensional tissues is a major research goal. A natural
      marine sponge skeleton was selected as a potential scaffold on the basis of the
      hydration potential of the fiber, the presence of open interconnected channels
      created by the fiber network, the collagenous composition of the fiber, and the
      structural diversity of fiber architecture. The skeleton of an undetermined
      species of Spongia (Class Demospongiae: Order Dictyoceratida: Family Spongiidae),
      composed of spongin, supported growth of human osteoprogenitor cells. Cell
      attachment and invasion into the framework were observed within 16 h, followed by
      development into membranous sheets between the sponge fibers by concentric
      infilling. Histochemical staining for alkaline phosphatase and type I collagen
      indicated formation of bone matrix as confirmed by birefringence. At 9 and 14
      days alkaline phosphatase-specific activity in sponge fiber-osteoprogenitor cell
      cultures was significantly greater than in control cultures on cell culture
      plastic. Adsorption with recombinant human bone morphogenetic protein 2 confirmed
      the potential of this sponge skeleton as a delivery scaffold for osteogenic
      factors. The abundance and structural diversity of natural marine sponge
      skeletons and their potential as multifunctional, cell conductive and inductive
      frameworks indicate a promising new source of scaffold for tissue regeneration.

PMID- 14670104
TI  - Tissue engineering for bone regeneration using differentiated alveolar bone cells
      in collagen scaffolds.
AB  - Regeneration of osseous defects by a tissue-engineering approach provides a novel
      means of treatment utilizing cell biology, materials science, and molecular
      biology. In this study the concept of tissue engineering was tested with collagen
      type I matrices seeded with cells with osteogenic potential and implanted into
      sites where osseous damage had occurred. Explant cultures of cells from human
      alveolar bone and gingiva were established. When seeded into a three-dimensional
      type I collagen-based scaffold, the bone-derived cells maintained their
      osteoblastic phenotype as monitored by mRNA and protein levels of the bone
      related proteins including bone sialoprotein, osteocalcin, osteopontin, bone
      morphogenetic proteins 2 and 4, and alkaline phosphatase. These in vitro
      developed matrices were implanted into critical-size bone defects in skulls of
      immunodeficient (SCID) mice. Wound healing was monitored for up to 4 weeks. When
      measured by microdensitometry the bone density within defects filled with
      osteoblast-derived matrix was significantly higher compared with defects filled
      with either collagen scaffold alone or collagen scaffold impregnated with
      gingival fibroblasts. New bone formation was found at all the sites treated with
      the osteoblast-derived matrix at 28 days, whereas no obvious new bone formation
      was identified at the same time point in the control groups. In situ
      hybridization for the human-specific Alu gene sequence indicated that the newly
      formed bone tissue resulted from both transplanted human osteoblasts and
      endogenous mesenchymal stem cells. The results indicate that cells derived from
      human alveolar bone can be incorporated into bioengineered scaffolds and
      synthesize a matrix, which on implantation can induce new bone formation.

PMID- 14670105
TI  - Bone formation by mesenchymal progenitor cells cultured on dense and microporous
      hydroxyapatite particles.
AB  - Hydroxyapatite (HA) microparticles, varying in size and microporosity, were
      evaluated in vitro and in vivo on their suitability to be used as a carrier in an
      injectable tissue engineered bone filler. Depending on their manufacturing
      method, either dense (HA-s) or microporous (HA-r) particles were produced in
      diameter ranges of 212-300 microm (HA-s and HA-r) and 500-706 microm (HA-s).
      After seeding and culturing goat mesenchymal progenitor cells on the various
      particles for 1 week, sheets were produced in which multilayers of cells and
      extracellular matrix held the particles together. Subcutaneous implantation of
      the constructs in nude mice for 4 weeks revealed abundant bone formation with the
      212 to 300-microm diameter particle range. Up to 30% bone was formed in the
      available areas between the individual microparticles, while bone marrow was
      present in the samples containing microporous particles. Surprisingly, no bone or
      bone marrow formation was apparent with the 500 to 706-microm diameter range
      particles. These results show that size and microporosity of HA microparticles
      affect the osteogenic potential of cultured cells and indicate that particles in
      a diameter range of 212-300 microm may be used toward the development of
      injectable formulations of tissue-engineered bone.

PMID- 14670106
TI  - Healing of artificial fenestration defects by seeding of fibroblast-like cells
      derived from regenerated periodontal ligament in a dog: a preliminary study.
AB  - The purpose of this study was to assess the seeding of fibroblast-like cells to
      promote periodontal healing in artificial fenestration defects in a dog.
      Fibroblast-like cells were cultured by incubating regenerated periodontal
      ligament tissue, that had been surgically taken, underneath a Teflon membrane.
      Fenestration defects were surgically induced on the maxillary canine and first
      molar teeth at a spacing of 5 to 5 mm. Passage 4 cells (2 x 10(5) cells) in
      autologous blood coagulum were placed on root surfaces in two defects; the
      remaining two defects were used as controls. Healing was evaluated
      histomorphometrically on postoperative day 42. The main periodontal healing
      pattern consisted of connective tissue adaptation in three of the four specimens
      including one control, with cementum formation at 9-12%; one control specimen
      that exhibited 100% cementum formation. New bone formation was greater in the
      cell-seeding group (84%) compared with control (39%). In the cell-seeding group,
      one specimen exhibited total regeneration of bone (100%); however, the connective
      tissue located between newly formed bone and the root surface was observed to
      adapt to the dentin surface, with limited cementum formation. Seeding of cells
      from periodontal ligament may be promising to promote periodontal regeneration,
      but needs to be investigated in further studies.

PMID- 14670107
TI  - Effects of medium perfusion rate on cell-seeded three-dimensional bone constructs
      in vitro.
AB  - Cellular activity at the center of tissue-engineered constructs in static culture
      is typically decreased relative to the construct periphery because of transport
      limitations. We have designed a tissue culture system that perfuses culture
      medium through three-dimensional (3D) porous cellular constructs to improve
      nutrient delivery and waste removal within the constructs. This study examined
      the effects of medium perfusion rate on cell viability, proliferation, and gene
      expression within cell-seeded 3D bone scaffolds. Human trabecular bone scaffolds
      were seeded with MC3T3-E1 osteoblast-like cells and perfused for 1 week at flow
      rates of 0.01, 0.1, 0.2, and 1.0 mL/min. Confocal microscopy after 1 week of
      culture indicated that a flow rate of 1.0 mL/min resulted in substantial cell
      death throughout the constructs whereas lowering the flow rate led to an
      increasing proportion of viable cells, particularly at the center of the
      constructs. DNA analysis showed increases in cell proliferation at a flow rate of
      0.01 mL/min relative to 0.2 mL/min and static controls. Conversely, mRNA
      expressions of Runx2, osteocalcin, and alkaline phosphatase were upregulated at
      0.2 mL/min compared with lower flow rates as quantified by real-time RT-PCR.
      These data suggest that medium perfusion may benefit the development of 3-D
      tissues in vitro by enhancing transport of nutrients and waste within the
      constructs and providing flow-mediated mechanical stimuli.

PMID- 14670108
TI  - Application of perfusion culture system improves in vitro and in vivo
      osteogenesis of bone marrow-derived osteoblastic cells in porous ceramic
      materials.
AB  - Composites of bone marrow-derived osteoblasts (BMOs) and porous ceramics have
      been widely used as a bone graft model for bone tissue engineering. Perfusion
      culture has potential utility for many cell types in three-dimensional (3D)
      culture. Our hypothesis was that perfusion of medium would increase the cell
      viability and biosynthetic activity of BMOs in porous ceramic materials, which
      would be revealed by increased levels of alkaline phosphate (ALP) activity and
      osteocalcin (OCN) and enhanced bone formation in vivo. For testing in vitro,
      BMO/beta-tricalcium phosphate composites were cultured in a perfusion container
      (Minucells and Minutissue, Bad Abbach, Germany) with fresh medium delivered at a
      rate of 2 mL/h by a peristaltic pump. The ALP activity and OCN content of
      composites were measured at the end of 1, 2, 3, and 4 weeks of subculture. For
      testing in vivo, after subculturing for 2 weeks, the composites were
      subcutaneously implanted into syngeneic rats. These implants were harvested 4 or
      8 weeks later. The samples then underwent a biochemical analysis of ALP activity
      and OCN content and were observed by light microscopy. The levels of ALP activity
      and OCN in the composites were significantly higher in the perfusion group than
      in the control group (p < 0.01), both in vitro and in vivo. Histomorphometric
      analysis of the hematoxylin- and eosin-stained sections revealed a higher average
      ratio of bone to pore in BMO/beta-TCP composites of the perfusion group after
      implantation: 47.64 +/- 6.16 for the perfusion group and 26.22 +/- 4.84 for
      control at 4 weeks (n = 6, p < 0.01); 67.97 +/- 3.58 for the perfusion group and
      47.39 +/- 4.10 for control at 8 weeks (n = 6, p < 0.05). These results show that
      the application of a perfusion culture system during the subculture of BMOs in a
      porous ceramic scaffold is beneficial to their osteogenesis. After
      differentiation culture in vitro with the perfusion culture system, the activity
      of the osteoblastic cells and the consequent bone formation in vivo were
      significantly enhanced. These results suggest that the perfusion culture system
      is a valuable and convenient tool for applications in tissue engineering,
      especially in the generation of artificial bone tissue.

PMID- 14670109
TI  - Chondrogenesis of aged human articular cartilage in a scaffold-free bioreactor.
AB  - Chondrogenesis of aged human articular chondrocytes was evaluated under
      controlled in vitro conditions, using a rotating bioreactor vessel. Articular
      chondrocytes isolated from 10 aged patients (median age, 84 years) were increased
      in monolayer culture. A single-cell suspension of dedifferentiated chondrocytes
      was inoculated in a rotating wall vessel, without the use of any scaffold or
      supporting gel material. After 90 days of cultivation, a three-dimensional
      cartilage-like tissue was formed, encapsulated by fibrous tissue resembling a
      perichondrial membrane. Morphological examination revealed differentiated
      chondrocytes ordered in clusters within a continuous dense cartilaginous matrix
      demonstrating a strong positive staining with monoclonal antibodies against
      collagen type II and articular proteoglycan. The surrounding fibrous membrane
      consisted of fibroblast-like cells, and showed a clear distinction from the
      cartilaginous areas when stained against collagen type I. Transmission electron
      microscopy revealed differentiated and highly metabolically active chondrocytes,
      producing an extracellular matrix consisting of a fine network of randomly
      distributed cross-banded collagen fibrils. Chondrogenesis of aged human articular
      chondrocytes can be induced in vitro in a rotating bioreactor vessel using low
      shear and efficient mass transfer. Moreover, the tissue-engineered constructs may
      be used for further in vitro studies of differentiation, aging, and regeneration
      of human articular cartilage.

PMID- 14670110
TI  - Effect of implantation site on hepatocytes heterotopically transplanted on
      biodegradable polymer scaffolds.
AB  - We investigated the engraftment of heterotopically transplanted hepatocytes in
      three sites: the subcutaneous space, the small intestinal mesentery, and the
      omentum to determine the optimal location for tissue-engineered liver constructs.
      Hepatocytes were isolated from inbred Lewis rats and placed on polymer
      constructs. Cell-polymer constructs were implanted into the subcutaneous space of
      the abdominal wall, the small intestinal mesentery, and the omentum of Lewis
      rats. One group of rats had undergone previous portacaval shunt. Animals were
      killed 2 or 4 weeks after implantation and the constructs were analyzed for
      engraftment, using computer-assisted morphometric analysis. Engraftment was
      greatest in the omentum with less engraftment in the mesentery. There was minimal
      engraftment in the subcutaneous space in all specimens. Prior portacaval shunt
      increased engraftment in the mesentery and the omentum, but not the subcutaneous
      space. The omentum is the most favorable bed for engraftment of hepatocyte
      polymer tissue-engineered constructs and the addition of a portacaval shunt
      increases survival of transplanted hepatocytes in the omentum and mesentery.

PMID- 14670111
TI  - Fabrication of mitral valve chordae by directed collagen gel shrinkage.
AB  - The principles of tissue engineering are being used to explore numerous
      applications in reconstructive surgery. Mitral valve chordae are one such
      potential area, as mitral valve repair is increasing in popularity and synthetic
      materials have not been used widely. The use of cells, combined with
      reconstituted type I collagen, is an attractive option for fabricating materials
      for the replacement of thin tendonous structures such as mitral valve chordae. We
      have been using the principle of directed collagen gel shrinkage to fabricate
      tendinous structures with good mechanical properties. In this study, our
      objective was to maximize the strength of the collagen constructs by choosing
      cell type and optimizing cell-seeding density, culture time, and initial collagen
      concentration. A collagen-cell suspension was cast into silicone rubber wells
      with microporous anchors at the ends and cultured in an incubator. The anchors
      allowed shrinkage to occur only transverse to the long axis of the wells, thus
      creating highly aligned collagenous constructs. Collagen gel contraction
      increased with higher cell-seeding density. The optimal value was 10(6) cells/mL.
      The rate of gel contraction decreased with the initial collagen concentration.
      Fibril density increased with culture time, as the gel contracted. After the
      system was optimized, the mechanical strength of the constructs increased to 1.1
      MPa, a value at least an order of magnitude greater than previously published
      results with similar systems. This study has demonstrated that collagen-cell
      constructs, with material properties similar to those of native mitral valve
      chordae, can be developed using the principle of directed collagen gel shrinkage.
      These structures may have application in other areas that require small-diameter
      tendons.

PMID- 14670112
TI  - Cultivation in rotating bioreactors promotes maintenance of cardiac myocyte
      electrophysiology and molecular properties.
AB  - We tested the hypothesis that cardiomyocytes maintained their phenotype better if
      cultured as three-dimensional tissue constructs than if cultured as confluent
      monolayers. Neonatal rat cardiomyocytes were cultured on biomaterial scaffolds in
      rotating bioreactors for 1 week, and resulting tissue constructs were compared
      with confluent monolayers and slices of native ventricular tissue with respect to
      proteins involved in cell metabolism (creatine kinase isoform MM), contractile
      function (sarcomeric myosin heavy chain), and intercellular communication
      (connexin 43), as well as action potential characteristics (e.g., membrane
      resting potential, maximum depolarization slope, and action potential duration),
      and macroscopic electrophysiological properties (maximum capture rate). The
      molecular and electrophysiological properties of cardiomyocytes cultured in
      tissue constructs, although inferior to those of native neonatal ventricles, were
      superior to those of the same cells cultured as monolayers. Construct levels of
      creatine kinase, myosin heavy chain, and connexin 43 were 40-60% as high as
      ventricle levels, whereas monolayer levels of the same proteins were only 11-20%
      as high. Construct action potential durations were 1.8-fold higher than those in
      ventricles, whereas monolayer action potential durations were 2.4-fold higher.
      Pharmacological studies using 4-aminopyridine showed that prolonged action
      potential duration and reduced maximum capture rate in tissue constructs as
      compared with native ventricles could be explained by decreased transient outward
      potassium current.

PMID- 14670113
TI  - Angiogenesis in tissue-engineered small intestine.
AB  - Tissue-engineered intestine offers promise as a potential novel therapy for short
      bowel syndrome. In this study we characterized the microvasculature and
      angiogenic growth factor profile of the engineered intestine. Twenty-three tissue
      engineered small intestinal grafts were harvested from Lewis rat recipients 1 to
      8 weeks after implantation. Architectural similarity to native bowel obtained
      from juvenile rats was assessed with hematoxylin and eosin-stained sections.
      Capillary density, measured after immunohistochemical staining for CD34, was
      expressed as number of capillaries per 1000 nuclei. Vascular endothelial growth
      factor (VEGF) and basic fibroblast growth factor (bFGF) tissue levels were
      measured by ELISA and normalized to total protein. Over the 8-week period cysts
      increased in volume (0.5 cm(3) at week 1 versus 12.6 cm(3) at week 8) and mass
      (1.30 +/- 0.29 versus 9.74 +/- 0.3 g; mean +/- SEM). Muscular and mucosal layers
      increased in thickness, but capillary density remained constant (82.95 +/- 4.81
      capillaries per 1000 nuclei). The VEGF level was significantly higher in juvenile
      rat bowel than in engineered cyst (147.6 +/- 23.9 versus 42.3 +/- 3.4 pg/mg; p <
      0.001). Tissue bFGF levels were also higher (315 +/- 65.48 versus 162.3 +/- 15.09
      pg/mg; p < 0.05). The mechanism driving angiogenesis differs in engineered
      intestine and in normal bowel. VEGF and bFGF delivery may prove useful for
      bioengineering of intestine.

PMID- 14670114
TI  - Engineered adipose tissue supplied by functional microvessels.
AB  - A volume-persistent culture of adipose tissue under in vivo conditions can be
      achieved only by early vascularization after cell transplantation.
      Cotransplantation of autologous preadipocytes with endothelial cells may enable
      the early formation of a capillary network. Investigations were performed in vivo
      in a specially adapted chorioallantoic membrane (CAM) model. Fertilized White
      Leghorn eggs were incubated and opened on day 3 of incubation and human dermal
      microvascular endothelial cell (HDMVEC) spheroids and preadipocytes were
      transferred in a fibrin matrix to the CAM. On day 7 after incubation the
      composites were explanted and immunohistologically investigated. Numerous vessels
      consisting of HDMVECs could be detected and the lumena of these vessels were
      perfused by chick erythrocytes. These results show the formation of a capillary
      network consisting of transplanted HDMVECs. The microcirculation of chick
      erythrocytes in vessels consisting of human endothelial cells proves the
      continuity of a newly formed capillary system to the host vessel system. The
      experiments demonstrate the first patent connection of tissue-engineered
      microvessels in adipose tissue to a host vessel system without applying exogenous
      angiogenic growth factors or transient transfection. The cotransplantation of
      endothelial cell spheroids with angiogenic mesenchymal cells may lead to the
      engineering of complex three-dimensional implants.

PMID- 14670115
TI  - Biomaterial mesh seeded with vascular remnants from a quail embryo has a
      significant and fast vascular templating effect on host implant tissue.
AB  - Seeding biomaterial implants with vascular remnants has the potential to
      facilitate host vessel ingrowth via a vascular templating effect. Vessels from
      quail embryo were grown into a polyurethane fibroporous mesh and the samples were
      frozen-thawed and then implanted in rat subcutaneous dorsum. Results show that
      the process of revascularization, using the quail vessel remnants, occurred over
      the first 3 days after implantation and resulted in functional vessels. Rat
      endothelial cells were found in the quail templates on day 1. On day 2 the
      endothelial cells formed a confluent layer and started producing laminin. By this
      time approximately 70% of the rat vessel tissue in the implant had grown into
      quail vascular remnants, indicating that the quail vessels were extensively used
      as templates for host vessel ingrowth. Laminin production was increased and
      collagen production started by day 3, at which time the vessels were functional
      in that rat blood flowed through them. At 2 weeks host vessel density was
      approximately twice that of control samples; thus the implant substantially
      enhanced the size of the vascular network. For meshes that additionally received
      vascular endothelial growth factor (VEGF) seeding before implantation, vessel
      density at 2 weeks was enhanced over samples with quail embryo alone. However,
      the quail was found to have the greatest angiogenic effect above any of the
      implant components-quail, VEGF, and collagen. Tissue engineering of vessel
      templates may thus be a realistic solution to effective fast vascularization of
      biomaterials.

PMID- 14670116
TI  - Gene therapy in tissue-engineered blood vessels.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality in Western
      society. More than 1 million arterial bypass procedures are performed annually in
      the United States, where either autologous veins or synthetic grafts are used to
      replace arteries in the coronary or peripheral circulation. Tissue engineering of
      blood vessels from autologous cells has the potential to produce biological
      grafts for use in bypass surgery. Ex vivo development of vascular grafts also
      provides an ideal target of site-specific gene therapy to optimize the physiology
      of the developing conduit, and for the possible delivery of other therapeutic
      genes to a vascular bed of interest. In this article, we demonstrate that by
      using a novel retroviral gene delivery system, a target gene of interest can be
      specifically delivered to the endothelial cells of a developing engineered
      vessel. Further, we demonstrate that this technique results in stable
      incorporation of the delivered gene into the target endothelial cells for more
      than 30 days. These data demonstrate the utility of the retroviral gene delivery
      approach for optimizing the biologic phenotype of engineered vessels. This also
      provides the framework for testing an array of genes that may improve the
      function of engineered blood vessels after surgical implantation.

PMID- 14670117
TI  - Effects of transforming growth factor beta1 and dexamethasone on the growth and
      chondrogenic differentiation of adipose-derived stromal cells.
AB  - The effects of soluble mediators and medium supplements commonly used to induce
      chondrogenic differentiation in different cell culture systems were investigated
      to define their dose-response profiles and potentially synergistic effects on the
      chondrogenic differentiation of adipose-derived adult stromal (ADAS) cells. Human
      ADAS cells were suspended within alginate beads and cultured in basal medium with
      insulin, transferrin, and selenious acid (ITS+) or fetal bovine serum (FBS) and
      treated with different doses and combinations of TGF-beta1 (0, 1, and 10 ng/mL)
      and dexamethasone (0, 10, and 100 nM). Cell growth and chondrogenic
      differentiation were assessed by measuring DNA content, protein and proteoglycan
      synthesis rates, and proteoglycan accumulation. The combination of ITS+ and TGF
      beta1 significantly increased cell proliferation. Protein synthesis rates were
      increased by TGF-beta1 and dexamethasone in the presence of ITS+ or FBS. While
      TGF-beta1 significantly increased proteoglycan synthesis and accumulation by 1.5-
      to 2-fold in the presence of FBS, such effects were suppressed by dexamethasone.
      In summary, the combination of TGF-beta1 and ITS+ stimulated cell growth and
      synthesis of proteins and proteoglycans by human ADAS cells. The addition of
      dexamethasone appeared to amplify protein synthesis but had suppressive effects
      on proteoglycan synthesis and accumulation.

PMID- 14670118
TI  - Invention and business performance in the tissue-engineering industry.
AB  - Tissue engineering is a young and interdisciplinary scientific discipline but it
      offers exciting opportunities to improve the quality of health care for hundreds
      of thousands of patients. Lured by its potential, several start-up companies,
      pharmaceutical corporations, and medical device enterprises alike are investing
      heavily in this sector. Invention is a key driver of competition in this sector.
      In this study, we aim to explain the variation in inventive output across the
      different firms in the sector. Our major premise is that firms that forge
      alliances will be able to tap into the expertise of their partners and thus
      improve their chances of inventive output. We further argue that alliances that
      enable technology acquisition or learning will enhance the inventive output of
      firms more than other kinds of alliances. We measure the inventive output of a
      company by the number of patents filed. On the basis of a preliminary analysis of
      seven companies, we find support for the hypotheses. We also argue that, to
      achieve commercial success, firms need to manage time to market (through
      alliances or otherwise), have a global outlook, nurture their financial
      resources, and attain critical mass through mergers.

PMID- 14670119
TI  - Technique paper for wet-spinning poly(L-lactic acid) and poly(DL-lactide-co
      glycolide) monofilament fibers.
AB  - A simple and repeatable method is described for wet-spinning poly(L-lactic acid)
      (PLLA) and poly(DL-lactic-co-glycolic acid) (PLGA) monofilament fibers. These
      fibers are strong, elastic, and suitable for many applications, including use as
      tissue-engineering scaffolds. The PLLA wet-extruded fibers do not show additional
      strain-induced crystallization as a result of drawing the fibers during
      fabrication; however, there is an apparent increase in crystallinity late in the
      degradation process in saline at 37 degrees C. We have measured the molecular
      weight degradation in saline at 37 degrees C for fibers of both PLLA and PLGA.
      Changing solvent systems, polymer blends, and winding rates alters mechanical and
      morphological properties of these fibers for specific applications. The authors
      discuss a possible theoretical explanation for these observed changes due to
      changes in polymer concentration, solvent system, and coagulation bath
      properties. This wet-extrusion process is simple and inexpensive enough to be
      carried out in almost any laboratory interested in tissue engineering.

PMID- 14670121
TI  - In vivo evaluation of gene therapy vectors in ex vivo-derived marrow stromal
      cells for bone regeneration in a rat critical-size calvarial defect model.
AB  - Cells genetically modified to produce osteoinductive factors have potential for
      use in enhancing bone regeneration for reconstructive applications. Genetic
      modification of cells can be accomplished by a variety of gene therapy vectors.
      In this study we evaluated the ex vivo genetic modification of rat marrow stromal
      cells (MSCs) by adenoviral, retroviral, and cationic lipid vectors containing the
      gene for human bone morphogenetic protein 2 (hBMP-2). We investigated both the in
      vitro and in vivo osteogeneic potential of MSCs modified by each vector. In
      vitro, we found that only MSCs modified with the adenoviral vector produced
      detectable hBMP-2 and demonstrated a statistically significant increase in
      endogenous alkaline phosphatase activity indicative of osteogeneic
      differentiation. We further investigated the ability of genetically modified MSCs
      seeded on a titanium mesh scaffold to facilitate bone formation in vivo. In an
      orthotopic critical-size defect created in the rat cranium, bone formation was
      observed in all conditions with MSCs modified by the adenoviral vector
      demonstrating a small but statistically significant increase in bone formation
      relative to the other vectors and control. Implants in an ectopic location
      demonstrated minimal bone formation relative to the orthotopic location, with
      MSCs modified with cationic lipids forming less bone than the other vectors and
      control. Our results show that MSCs genetically modified with adenovirus
      containing the hBMP-2 gene had enhanced osteogeneic capacity relative to
      unmodified MSCs or MSCs modified by the other vectors. This study was the first
      to compare three different gene therapy vectors for the genetic modification of
      cells to produce osteoinductive factors for the purpose to enhance bone
      regeneration.

PMID- 14670122
TI  - In vivo selection of human hematopoietic cells in a xenograft model using
      combined pharmacologic and genetic manipulations.
AB  - Strategies that increase the ability of human hematopoietic stem and progenitor
      cells to repair alkylator-induced DNA damage may prevent the severe hematopoietic
      toxicity in patients with cancer undergoing high-dose alkylator therapy. In the
      context of genetic diseases, this approach may allow for selection of small
      numbers of cells that would not otherwise have a favorable growth advantage. No
      studies have tested this approach in vivo using human hematopoietic stem and
      progenitor cells. Human CD34(+) cells were transduced with a bicistronic
      oncoretrovirus vector that coexpresses a mutant form of O(6)-methylguanine DNA
      methyltransferase (MGMT(P140K)) and the enhanced green fluorescent protein (EGFP)
      and transplanted into nonobese diabetic/severe combined immunodeficient
      (NOD/SCID) mice. Mice were either not treated or treated with O(6)-benzylguanine
      (6BG) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). At 8-weeks postinjection,
      a 2- to 8-fold increase in the percentage of human CD45(+)EGFP(+) cells in
      6BG/BCNU-treated versus nontreated mice was observed in the bone marrow and was
      associated with increased MGMT(P140K)-repair activity. Functionally, 6BG/BCNU
      treated mice demonstrated multilineage differentiation in vivo, although some
      skewing in the maturation of myeloid and B cells was observed in mice
      transplanted with granulocyte-colony stimulating factor (G-CSF)-mobilized
      peripheral blood compared to umbilical cord blood. Expansion of human cells in
      6BG/BCNU-treated mice was observed in the majority of mice previously
      transplanted with transduced umbilical cord blood cells. In addition, a
      significant increase in the number of EGFP(+) progenitor colonies in treated
      versus nontreated mice were observed in highly engrafted mice indicating that
      selection and maintenance of human progenitor cells can be accomplished by
      expression of MGMT(P140K) and treatment with 6BG/BCNU.

PMID- 14670123
TI  - Liver toxicities typically induced by first-generation adenoviral vectors can be
      reduced by use of E1, E2b-deleted adenoviral vectors.
AB  - Adenoviral vectors from which the E1 region has been deleted ([E1(-)] Ad) are
      known to induce strong immune responses after systemic delivery. In this study we
      have evaluated liver toxicities in mice after intravenous injection with high
      doses of [E1(-)] or modified [E1(-), E2b(-)] Ad vectors (both expressing the
      bacterial beta-galactosidase [lacZ] marker gene) in C57BL/6, BALB/c, and SCID
      mice. Our data demonstrate a marked reduction in maximal liver toxicities and
      pathologies (typically noted at 21 days postinjection) with the use of the [E1(
      ), E2b(-)] modified vector in all strains of mice tested. Our data also
      demonstrated that despite the use of the [E1(-), E2b(-)] Ad vector, significant
      liver toxicities were still observed. To address this issue and the fact that the
      lacZ gene was perceived as a foreign antigen in the immune-competent C57BL/6 and
      BALB/c mice, we similarly injected mice tolerant of LacZ (lacZ-TG). In contrast
      to our studies in C57BL/6 and BALB/c mice, LacZ-TG mice exhibited virtually no
      evidence of hepatotoxicity after intravenous injection with the [E1(-), E2b(-)]
      vector, in contrast to use of the [E1(-)] Ad vector. Our results demonstrate that
      the [E1(-), E2b(-)] Ad vector class can reduce liver toxicities typically
      ascribed to Ad vector-mediated gene transfer after transfer of a highly
      immunogenic or foreign gene, whereas transfer of a transgene that is perceived as
      nonforeign by the host can be delivered with virtually no evidence of toxicity.
      On the basis of a careful review of the literature, these improvements in vector
      safety rival those noted with other, more significantly modified Ad vectors
      described to date.

PMID- 14670124
TI  - Comparison of murine leukemia virus, human immunodeficiency virus, and adeno
      associated virus vectors for gene transfer in multiple myeloma: lentiviral
      vectors demonstrate a striking capacity to transduce low-proliferating primary
      tumor cells.
AB  - Genetic modification of primary tumor cells by gene transfer is of major interest
      to study the role of specific genes in the biology of a given malignancy and to
      modify tumor cells for therapeutic use. Multiple myeloma (MM) is a low
      proliferating cancer, with often less than 1% of the cells in the S phase of the
      cell cycle. As primary myeloma cells are notoriously difficult to transduce, we
      conducted a comparison of various viral vectors, known to integrate the transgene
      of interest into the target genome, for their ability to stably promote the
      expression of an enhanced green fluorescent protein (EGFP) transgene. We compared
      three murine leukemia virus-based vectors, differing only in their viral
      envelope, a human immunodeficiency virus (HIV)-based vector pseudotyped with the
      vesicular stomatitis virus glycoprotein (VSV-G), and an adeno-associated virus
      type 2 vector. Transduction characteristics of these vectors were evaluated in
      human myeloma cell lines and in primary myeloma cells. Unequivocally, we observed
      that the VSV-G/HIV vector was the most efficient vector for transducing the cell
      lines and the only one able to transduce primary myeloma cells reproducibly. The
      mean percentage of transduced primary myeloma cells was 43.6% (range, 16.3
      77.6%), with one round of infection at a low multiplicity of infection, including
      MM cell samples with less than 1% of cells in the S phase. A quantitative
      polymerase chain reaction assay demonstrated that this more efficient EGFP
      expression was associated with a higher GFP copy number in the targeted cell. We
      propose that lentiviral vectors should be used for transduction of
      nonproliferating primary tumor cells such as myeloma cells.

PMID- 14670125
TI  - Gene therapy of anaplastic thyroid carcinoma with a single-chain interleukin-12
      fusion protein.
AB  - Anaplastic thyroid carcinoma is the most aggressive type of thyroid malignancy
      with a mean survival time of less than 8 months. No effective therapeutic
      approach is currently available, making the development of novel treatments
      necessary. Interleukin (IL)-12 is a proinflammatory heterodimeric cytokine with
      strong antitumor activity. In the present study, we investigated the potential of
      IL-12 gene therapy for anaplastic thyroid carcinoma in BALB/c (nu/nu) nude mice.
      A single-chain IL-12 fusion protein construct was created to assure equal
      expression of its p35 and p40 subunits. Human anaplastic thyroid carcinoma cell
      line ARO was stably transfected with an IL-12 expression plasmid under the
      control of cytomegalovirus (CMV) promoter (scIL-12/CMVpDNA). High levels of
      functional IL-12 (26.78 +/- 4.11 ng/ml per 10(6) cells per 48 hr) were produced
      by scIL-12-transfected ARO cells (ARO/IL-12). Tumorigenicity in nude mice was
      completely lost in scIL-12-transfected ARO cells, as demonstrated by the lack of
      tumor formation after subcutaneous injection of 2 x 10(6) ARO/IL-12 cells, even
      though there was no difference in cell proliferation between ARO and ARO/IL-12
      cells. Tumor growth was observed after challenge with ARO tumor cells, indicating
      that protective immunity had not developed against the parental cells.
      Furthermore, the growth rate of established subcutaneous ARO tumors was
      significantly reduced by either subcutaneous injection of 2 x 10(6) ARO/IL-12
      cells weekly or intramuscular injection of 50 microg scIL-12/CMVpDNA twice
      weekly. The antineoplastic activity of ARO/IL-12 cells was, however, abrogated by
      intraperitoneal injection of anti-natural killer (NK) cell antibody. Moreover,
      significantly higher number of ARO/IL-12 cells and ARO cells were killed by
      splenocytes from nude mice previously treated with ARO/IL-12 compared to those
      treated with ARO cells (32% vs. 9% when ARO were used as target cells, 43% vs.
      17% when ARO/IL12 were used as target cells; p < 0.01) in an in vitro
      cytotoxicity assay. Again, tumor cell killing was neutralized by the addition of
      anti-NK cell antibody in the assay. In conclusion, we have demonstrated
      successful gene therapy with a scIL-12 fusion protein against anaplastic thyroid
      carcinoma in an in vivo model. The immune response against ARO/IL-12 cells is
      mediated by NK cells. These results may set the stage for clinical application of
      IL-12 gene therapy for poorly differentiated thyroid carcinoma.

PMID- 14670126
TI  - Evidence that the mouse 3' kappa light chain enhancer confers position
      independent transgene expression in T- and B-lineage cells.
AB  - One of the major obstacles for successful application of murine leukemia virus
      (MLV) vectors to genetic therapy of lymphocyte disorders is low levels of
      transgene expression or the eventual loss of expression. To overcome this
      problem, an improved retroviral vector was constructed utilizing the
      myeloproliferative sarcoma virus (MPSV) long terminal repeat (LTR), which
      provided a significantly higher level of transgene expression in human lymphoid
      cells than did MLV vectors. Nevertheless, transgene expression remained low in a
      large percentage of transduced cells. To address whether lymphocyte enhancer
      elements might improve transgene expression mediated by retroviral vectors in
      lymphocytes, we cloned the mouse immunoglobulin 3' kappa light chain enhancer
      gene (mE3') into the MPSV vector. We found that the mE3' conferred a higher, more
      uniform and sustained level of expression in transduced T- and B-cell lines, and
      in primary T cells, than did the control vector lacking this element. Integration
      sites were diverse and a single copy of the proviral genome was present in all
      examined transduced cells. The mE3' failed to enhance transgene expression in
      most nonlymphoid cells, indicating it is relatively lineage-specific. Taken
      together, these results provide strong evidence that the mE3' functions as a
      locus control region (LCR) in conferring enhanced integration-site-independent
      expression of a retroviral transgene.

PMID- 14670127
TI  - Effective suppression of class I major histocompatibility complex expression by
      the US11 or ICP47 genes can be limited by cell type or interferon-gamma exposure.
AB  - An impediment encountered in many viral-based gene therapy clinical trials has
      been the rapid destruction of the transgene by the host's immune response. The
      processing and presentation of antigens through the class I major
      histocompatibility complex (MHC) pathway is the initial specific response to
      viral infection. Disruption of the class I MHC pathway by herpes simplex virus
      (HSV) or the human cytomegalovirus (HCMV) results in a decrease of the CD8(+)
      cytotoxic T lymphocyte (CTL) response and prolongs survival of infected cells in
      the host. Two viral immune suppression genes that interfere with the class I MHC
      presentation pathway, the HSV type I ICP47 gene and HCMV US11 gene, were cloned
      and each incorporated into a retroviral vector. HSV ICP47 and HCMV US11
      transgenes were expressed in multiple cells lines and compared for their
      abilities to reduce antigen presentation on the cell surface by class I MHC.
      Retroviral supernatants were used to transduce human, canine, and rat cell lines.
      Fluorescence-activated cell sorter (FACS) analysis of US11- and ICP47-transduced
      cell lines demonstrated substantial reductions in class I MHC cell surface
      expression in most cell lines except in rodent cells where ICP47 is
      nonfunctional. The decrease in the level of class I MHC expression for ICP47
      transduced cell lines ranged from 31-98% relative to negative controls. US11
      decreased class I cell surface MHC by 67-96%. When both ICP47 and US11 are
      expressed in human cells, a further reduction of class I MHC was observed. Next,
      human A375 melanoma cells were tested to determine if the resulting reduction in
      cell surface class I MHC would reduce in vitro cytotoxicity by CTL. A375 cells
      expressing either ICP47 or US11 demonstrated a twofold to threefold reduction of
      specific lysis by primed CD8(+) CTL. These data clearly establish an ability to
      convey immune protection to human cells by viral genes. However, further analysis
      demonstrated that interferon (IFN)-gamma could reverse part or all of the
      downregulation of class I MHC induced by the ICP47 or US11 genes. The ICP47 and
      US11 genes, when expressed in target cells, decrease class I MHC presentation and
      as such might be used in strategies to create local immunosuppression against
      transgenes or allografts.

PMID- 14670128
TI  - Intravascular delivery of neural stem cell lines to target intracranial and
      extracranial tumors of neural and non-neural origin.
AB  - The remarkable migratory and tumor-tropic capacities of neural stem cells (NSCs
      and/or neuroprogenitor cells) represent a potentially powerful approach to the
      treatment of invasive brain tumors, such as malignant gliomas. We have previously
      shown that whether implanted directly into or at distant sites from an
      experimental intracranial glioma, NSCs distributed efficiently throughout the
      main tumor mass and also tracked advancing tumor cells, while stably expressing a
      reporter transgene. As therapeutic proof-of-concept, NSCs genetically modified to
      produce the prodrug activating enzyme cytosine deaminase (CD), effected an 80%
      reduction in the resultant tumor mass, when tumor animals were treated with the
      systemic prodrug, 5-fluorocytosine. We now extend our findings of the tumor
      tropic properties of NSCs (using a well-characterized, clonal NSC line C17.2), by
      investigating their capacity to target both intracranial and extracranial tumors,
      when administered into the peripheral vasculature. We furthermore demonstrate
      their capacity to target extracranial non-neural tumors such as prostate cancer
      and malignant melanoma. Well-characterized NSC lines (lacZ and/or CD-positive)
      were injected into the tail vein of adult nude mice with established experimental
      intracranial and/or subcutaneous flank tumors of neural and non-neural origin.
      The time course and distribution of NSCs within the tumor and internal organs was
      assessed in various models. Resulting data suggest that NSCs can localize to
      various tumor sites when injected via the peripheral vasculature, with little
      accumulation in normal tissues. Our findings suggest the novel use of
      intravascularly administered NSCs as an effective delivery vehicle to target and
      disseminate therapeutic agents to invasive tumors of neural and nonneural origin,
      both within and outside of the brain.

PMID- 14670129
TI  - Retroviral immunotoxin gene therapy of leukemia in mice using leukemia-specific T
      cells transduced with an interleukin-3/Bax fusion protein gene.
AB  - In past studies, we showed that T cells transduced with retroviral diphtheria
      immunotoxin (IT) target genes could serve as vehicles for delivering IT to tumors
      in vivo. We took advantage of the observation that antigen-specific T cells are
      able to penetrate tumors to design an approach delivering combined cellular and
      humoral therapy directly to the tumor site. To improve tumor specificity, we
      selected interleukin (IL)-3 as a ligand because its receptor is selectively
      overexpressed on myeloid leukemia progenitors. Because Bcl-2 family proteins show
      structural similarity to diphtheria toxin (DT), we constructed a unique
      retroviral IT using Bax, a proapoptotic member of the Bcl-2 family, in place of
      DT. Bax was chosen because several studies showed that its transduction induces
      lethal apoptosis in different cancers. The retroviral construct for gene therapy
      included IL-3 positioned downstream of its 80 amino acid leader, and permitted
      cotranslational protein synthesis of hybrid IL-3/human Bax fusion protein. Other
      vectors were constructed with IL-3 fused to DT or Pseudomonas exotoxin.
      Retroviral vectors were used to transiently transduce C8, a CD4(+) T cell clone
      that specifically recognized FBL-3, a lethal myeloid leukemia. Supernatants
      collected from transduced cells showed proapoptotic activity and selectively
      inhibited FBL-3 cells in vitro. Intraperitoneal injection of transduced but not
      nontransduced C8 into mice with subcutaneous tumors or systemic cancer
      significantly inhibited tumor growth. These results indicate that retroviral IT
      made with IL-3 and various toxic proteins may be useful in patients with acute
      myelogenous leukemia (AML). Furthermore, the Bax construct may be particularly
      useful as a nonimmunogenic substitute for bacterial toxins in retIT.

PMID- 14670130
TI  - Lentiviral vector-mediated delivery of short hairpin RNA results in persistent
      knockdown of gene expression in mouse brain.
AB  - RNA interference (RNAi) is an evolutionarily conserved mechanism of
      posttranscriptional gene-specific silencing. For in vivo applications, RNAi has
      been hampered until recently by inefficient delivery methods and by the transient
      nature of the gene suppression. Lentiviral vectors (LVs) hold great promise for
      gene therapeutic applications, pharmaceutical target validation, and functional
      genomics because stable gene transfer is mediated both in dividing and
      nondividing cells. We have used a lentiviral vector-based system for RNAi. We
      produced human immunodeficiency virus type 1-derived LVs encoding a short hairpin
      RNA specific for enhanced green fluorescent protein (EGFP) mRNA that were capable
      of inhibiting EGFP expression in mammalian cells. EGFP knockdown persisted after
      multiple passages of the cells. Of particular interest, our RNAi LVs were equally
      effective in suppression and prevention of EGFP expression after stereotactic
      injection in adult mouse brain. Therefore, we believe that the use of LVs for
      stable RNAi in brain will become a powerful aid to probe gene function in vivo
      and for gene therapy of diseases of the central nervous system.

PMID- 14670131
TI  - Mechanisms underlying postmortem redistribution of drugs: a review.
AB  - Postmortem drug concentrations do not necessarily reflect concentrations at the
      time of death, as drug levels may vary according to the sampling site and the
      interval between death and specimen collection. These site- and time-dependent
      variations are called "postmortem redistribution" (PMR). The underlying
      mechanisms are complex and of different types. Passive drug release from drug
      reservoirs such as the gastrointestinal tract, liver, lungs, and myocardium may
      occur immediately after death and, later on, cell autolysis and the putrefactive
      process participate in redistribution. There is evidence that basic lipophilic
      drugs with a large distribution volume are particularly susceptible to PMR.
      Nevertheless, this cannot explain the actual PMR of some nonbasic, nonlipophilic
      drugs. In addition, the persistence of drug metabolism immediately after death
      must be considered. Consequently, it is of great importance to analyze specimens
      from different sampling sites in order to detect potential PMR and avoid
      misinterpretation of results.

PMID- 14670132
TI  - The effect of hair color on the incorporation of codeine into human hair.
AB  - The influence of melanin on the binding of xenobiotics in hair will impact the
      interpretation of drug concentrations determined by hair testing. The purpose of
      this study was to determine if codeine, as a model compound of abused drugs,
      would be incorporated into black, brown, blond, or red hair as a function of
      melanin concentration. Such data would assist in the interpretation of codeine
      concentrations in hair and help elucidate the potential influence of hair color
      on incorporation of drugs. Male and female Caucasians with black (n = 6), brown
      (n = 12), blond (n = 8), or red hair (n = 6) and non-Caucasians with black hair
      (n = 12) aged 21-40 years were enrolled in the study. Each subject was
      administered oral codeine phosphate syrup in a dosage of 30 mg three times a day
      for five days. Twenty-four hours after the end of the treatment period, a 30-mg
      codeine dose was administered and the subject's plasma area under the
      concentration time curve (AUC) for codeine was determined. Codeine and melanin
      were measured in the first 3 cm of hair closest to the vertex region of the scalp
      prior to and 1, 4, 5, 6, and 7 weeks after dosing. The quantitative and
      qualitative melanin profiles were determined for each subject's hair to provide
      an objective measure of hair color. The plasma concentrations of codeine were
      measured to eliminate differences in the bioavailability and clearance of codeine
      as factors that might account for the differences in codeine hair concentrations.
      The subjects were asked not to cut their hair in the vertex region of the scalp
      or to use any form of chemical treatment on their hair, but otherwise normal
      hygienic measures were permitted. The mean (+/- SE) hair codeine concentrations 5
      weeks after dosing were 1429 (+/- 249) pg/mg in black hair; 208 (+/- 17) pg/mg in
      brown hair; 99 (+/- 10) pg/mg in blond hair; and 69 (+/- 11) in red hair pg/mg.
      In black hair, codeine concentrations were 2564 (+/- 170) pg/mg for Asians and
      865 (+/- 162) pg/mg for Caucasians. Similar concentration relationships were
      observed at weeks 4, 6, and 7. A strong relationship between the hair
      concentrations of codeine and melanin (R(2) = 0.73) was observed. Normalization
      of the codeine concentration with the melanin concentration reduced the hair
      color differences observed. These data demonstrate that the interpretation and
      reporting of hair test results for codeine are influenced by hair color. After
      this dosing protocol, the proposed federal guideline cutoff of 200 pg/mg of
      codeine would result in 100% of subjects with black hair and 50% of subjects with
      brown hair being reported as positive, and subjects with blond or red hair would
      be reported as negative. The incorporation of these drugs into hair should be
      studied carefully in humans to ensure the appropriate interpretation of drug
      concentrations.

PMID- 14670133
TI  - Concentrations and ratios of amphetamine, methamphetamine, MDA, MDMA, and MDEA
      enantiomers determined in plasma samples from clinical toxicology and driving
      under the influence of drugs cases by GC-NICI-MS.
AB  - Enantiomers of amphetamine (AM), methamphetamine (MA), 3,4
      methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and
      3,4-methylenedioxyethylamphetamine (MDEA) exhibit different pharmacological
      properties. This may be important for the interpretation of analytical results.
      Plasma samples were analyzed using validated negative ion chemical ionization gas
      chromatography-mass spectrometry procedures. The results for clinical toxicology
      cases, divided into screening (SCR) and intoxication (ITX) cases, and those of
      driving under the influence of drugs (DUID) cases were compared. The
      concentrations of all enantiomers, except R-(-)-MDA and R-(-)- and S-(+)-MA, in
      the SCR samples were lower than in ITX and DUID samples. Differences between
      concentrations in ITX and DUID samples were only significant for both enantiomers
      of AM (DUID higher). These findings suggested impairment in drugged drivers.
      Different enantiomer ratios (R vs. S) were found for AM between DUID and SCR
      samples, for MDMA between ITX and SCR samples, and for MDA between DUID and ITX
      and DUID and SCR samples. Higher MDMA enantiomer ratios in SCR compared to ITX
      samples are in accordance with a previously described increase of those ratios
      over time, possibly allowing differentiation of recent from nonrecent ingestion.
      Pharmacokinetic analysis of a MDMA poisoning yielded elimination half-lives of
      6.0 h for R-(-)-MDMA and 4.1 h for S-(+)-MDMA. The enantiomer ratios rose
      exponentially over time.

PMID- 14670134
TI  - Piperazine-derived designer drug 1-(3-chlorophenyl)piperazine (mCPP): GC-MS
      studies on its metabolism and its toxicological detection in rat urine including
      analytical differentiation from its precursor drugs trazodone and nefazodone.
AB  - Studies on the metabolism and the toxicological analysis of the piperazine
      derived designer drug 1-(3-chlorophenyl)piperazine (mCPP) in rat urine using gas
      chromatography-mass spectrometry (GC-MS) are described. mCPP was extensively
      metabolized, mainly by hydroxylation of the aromatic ring and by degradation of
      the piperazine moiety to the following metabolites: two hydroxy-mCPP isomers, N
      (3-chlorophenyl)ethylenediamine, 3-chloroaniline, and two hydroxy-3-chloroaniline
      isomers. The hydroxy-mCPP metabolites were partially excreted as the
      corresponding glucuronides and/or sulfates, and the aniline derivatives were
      partially acetylated to N-acetyl-hydroxy-3-chloroaniline isomers and N-acetyl-3
      chloroaniline. Our systematic toxicological analysis (STA) procedure using full
      scan GC-MS after acid hydrolysis, liquid-liquid extraction, and microwave
      assisted acetylation allowed the detection of mCPP and its previously mentioned
      metabolites in rat urine after single administration of a dose calculated from
      the doses commonly taken by drug users. The hydroxy-mCPP metabolites should be
      used as target analytes being the major metabolites of mCPP. Assuming similar
      metabolism, our STA procedure should be suitable for detection of an intake of
      mCPP in human urine. Furthermore, possibilities for differentiating an intake of
      mCPP from that of its precursor drugs trazodone or nefazodone, two common
      antidepressants, are described. Within the context of these studies, N-(3
      chlorophenyl)ethylenediamine was identified as a new metabolite of these two
      antidepressants.

PMID- 14670135
TI  - Quantitative identification of atrazine and its chlorinated metabolites in
      plasma.
AB  - The objective of this study was to develop an analytical method to detect and
      quantitate the chlorotriazine herbicide atrazine (ATRA), and its chlorinated
      metabolites [desethylatrazine (DE-ATRA), desisopropylatrazine (DI-ATRA), and
      diaminochlorotriazine (DACT)] in plasma. Control plasma separated from whole rat
      blood was fortified with known concentrations of ATRA, DE-ATRA, DI-ATRA, and
      DACT. These compounds were extracted from the plasma using a liquid-liquid
      extraction technique, and the resulting extracts were derivatized with tetrabutyl
      ammonium hydroxide and methyl iodide to produce methylated derivatives of ATRA
      and its chlorinated metabolites. Derivatized samples and standards were analyzed
      using gas chromatography-mass spectrometry with selected ion monitoring.
      Recoveries of fortified plasma samples ranged from 84% to 97% and were validated
      to 100 ng/mL. This analytical method was subsequently verified in a small-scale
      animal study to determine time course concentrations of chlorotriazines in plasma
      following a single oral gavage dose of ATRA to female Sprague Dawley rats.

PMID- 14670136
TI  - Determination of endogenous levels of GHB in human hair. Are there possibilities
      for the identification of GHB administration through hair analysis in cases of
      drug-facilitated sexual assault?
AB  - We have developed a GC-MS-MS assay for GHB in human hair. Five milligrams of
      washed hair were hydrolyzed by 1M or 0.01M NaOH before a liquid-liquid extraction
      with ethyl acetate under acidic conditions. GHB-d(6) was used as the internal
      standard. TMS derivatives were formed before injection. TBDMS derivatives were
      used in cases of strong chromatographic interferences or in a confirmatory
      procedure. Analysis of basal levels of GHB in 61 drug-free donors gave the
      following results: the mean measured concentration for blond hair was 0.60 ng/mg
      (n = 12), SD = 0.19 ng/mg, and extreme figures were in the range 0.35-0.95 ng/mg.
      For brown hair, the mean measured concentration was 0.90 ng/mg (n = 30), SD =
      0.42 ng/mg, and extreme figures 0.41-1.86 ng/mg. For black hair, the mean
      measured concentration was 0.90 ng/mg (n = 19), SD = 0.37 ng/mg, and extreme
      figures 0.32-1.54 ng/mg, showing no significant differences depending on hair
      color. Analysis of basal levels of GHB of 12 or more specimens in segmented hair
      showed a mean concentration of 1.22 ng/mg (0.31-8.4 ng/mg) and a relative
      standard deviation for each individual ranging from 6.75% to 37.98%. GHB was
      administered to a healthy 53-year-old white male (light brown hair) at oral
      dosages of 30, 45, and 60 mg/kg. Beard hair was collected just before
      administration and 24 h after (and each day for one week for the last dose), and
      a 7.5-cm scalp hair lock was collected 7 days after the last dose. A rise in GHB
      concentration was observed in beard hair for the 45 and 60 mg/kg dosages with a
      maximum at 24 h, whereas no change was observed for the 30 mg/kg dosage. Scalp
      hair was segmented into 3-mm long segments. The three proximal last segments
      showed significantly (0.0005 < p < 0.005) different concentrations of GHB (1.22,
      1.27, and 1.66 ng/mg, respectively) when compared with the basal physiological
      level of GHB in this same person (mean = 0.62 ng/mg, SD = 0.15 ng/mg). A case of
      daily GHB abuse during bodybuilding allowed us to determine a concentration of
      GHB of 14 ng/mg, in a 2-cm long segment (black hair). A case of rape under the
      influence of GHB was documented through hair analysis (black hair) and positive
      analysis of the glass she used. Sampled 7 days after the sexual assault, the
      three last 3-mm long proximal segments tested for GHB exhibited concentrations of
      3.1-5.3 and 4.3 ng/mg, respectively, whereas the mean physiological level
      determined in this woman was 0.71 ng/mg, SD = 0.17 ng/mg. The authors advise a
      two-step hair sampling as evidence of GHB consumption: the first sample at the
      time of exposure to show the contamination by sweat of the proximal segment in
      case of recent administration with a significant rise of hair level at the root,
      and the second after at least 3 or 4 weeks to avoid this contamination and
      determine the levels incorporated in the hair matrix before, during, and after
      the exposure.

PMID- 14670137
TI  - Validation of the Cozart microplate ELISA for detection of opiates in hair.
AB  - The purpose of this study was to determine the performance characteristics of the
      Cozart Opiates Microplate ELISA assay for the detection of opiates in hair
      specimens. One hundred and six hair specimens were collected from volunteers and
      from drug-related deaths. The hair samples were extracted by sonication followed
      by overnight extraction in methanol at 60 degrees C. The methanol extract was
      dried, reconstituted in ELISA negative calibrator, and then analyzed. For gas
      chromatography-mass spectrometry (GC-MS) analysis, deuterated internal standard
      mixture and 0.1M HCl were added to 20 mg of specimen or spiked blank hair and
      sonicated for 1 h. The opiates were extracted by solid-phase and derivatized with
      BSTFA + 1% TMS for GC-MS analysis. Fifty-one hair specimens were confirmed
      positive by GC-MS. 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
      as the reference method. The optimum cutoff for the Cozart Opiate Microplate
      ELISA was determined to be between 200 and 300 pg morphine equivalents/mg hair
      using a 20-mg hair sample. The Cozart Opiates Microplate EIA for opiates in hair
      using a cutoff of 200 pg/mg hair with a 20-mg hair sample had a sensitivity of
      98% +/- 2% and a specificity of 92.7% +/- 3.5% versus GC-MS.

PMID- 14670138
TI  - Performance of a microtiter plate ELISA for screening of postmortem blood for
      cocaine and metabolites.
AB  - The object of this study was to evaluate the suitability of the Neogen
      Corporation microtiter plate enzyme-linked immunoassay (ELISA) for cocaine and
      metabolites for screening of postmortem blood. Sixty-five postmortem whole blood
      specimens were obtained from drug-involved deaths that had been screened and
      confirmed positive for cocaine and/or benzoylecgonine (BE). Fifty-eight negative
      specimens were obtained from noncocaine-involved deaths. Specimens were tested
      using the Neogen Cocaine/BE microtiter plate ELISA assay. No matrix effects were
      found for whole blood in this assay. The effect of dilutions of the whole blood
      specimens of 1:5 through 1:50 was studied. A dilution of 1:5 was chosen to
      correspond to that used for other Neogen microtiter plate assays for drugs in
      whole blood. True positives, true negatives, false positives, and false negatives
      were determined and graphed for the ELISA results against gas chromatography-mass
      spectrometry (GC-MS), GC-nitrogen-phosphorus detection, and case histories. From
      these graphs and the receiver operating characteristic curves, the optimal cutoff
      for the Neogen Cocaine/BE ELISA was found to be 5 ng/mL BE equivalents at a 1:5
      dilution. The optimum cutoff for a 1:50 dilution was 50 ng/mL BE equivalents. The
      Neogen Cocaine/BE ELISA had a sensitivity of 93.8% +/- 2.9% and a specificity of
      96.6% +/- 2.4% versus GC-MS at a cutoff of 5 ng/mL BE equivalents (1:5 dilution)
      and a sensitivity of 100% +/- 0.5% and specificity of 98.3% +/- 1.7% versus GC-MS
      at a 50 ng/mL BE equivalents cutoff (1:50 dilution).

PMID- 14670139
TI  - Analysis of metformin in antemortem serum and postmortem specimens by a novel
      HPLC method and application to an intoxication case.
AB  - A case of intoxication from the oral hypoglycemic drug metformin is presented. A
      number of published liquid chromatographic methods were combined to enable a
      simplified analysis of metformin in both antemortem and postmortem specimens. The
      method involved direct injection of a protein-free filtrate into the liquid
      chromatograph. The method was sufficiently sensitive to detect therapeutic use of
      metformin; no common therapeutic or abused drugs interfered with the assay. In
      the presented case, the hospital admission serum metformin concentration was 141
      mg/L, or approximately two orders of magnitude above therapeutic concentrations.
      The medical examiner concluded that the cause of death in this case was metformin
      intoxication, and the manner of death was suicide.

PMID- 14670140
TI  - Fatal propafenone overdoses: case reports and a review of the literature.
AB  - First synthesized in 1970, propafenone is a frequently used 1C antiarrhythmic
      drug metabolized into two major metabolites, 5-hydroxypropafenone and
      norpropafenone. Paradoxically, fatal intoxication is rarely described, and only
      six cases have been reported in the literature. We report our experience with two
      patients found dead of self-inflicted poisoning where the propafenone blood
      concentration was very high (one concentration to our knowledge is one of the
      highest reported in the literature). At autopsy, no evidence of significant
      pathological disease were found. Propafenone was detected in blood by gas
      chromatography-mass spectrometry and by high-performance liquid chromatography
      using a diode-array detector, respectively, as propafenone artifact and
      propafenone. Blood propafenone concentrations were 4180 ng/mL and 9123 ng/mL. The
      literature regarding propafenone pharmacokinetic and intoxication is reviewed,
      and we discuss the low death rate attributed to this drug in contrast to its
      frequent use.

PMID- 14670141
TI  - Intranasal steroid sprays in the treatment of rhinitis: is one better than
      another?
AB  - The treatment of allergic rhinitis has been revolutionized by the introduction of
      topical nasal steroids, which are one of the commonest prescriptions from
      otolaryngology departments. With so many different sprays available on the
      market, the literature was reviewed for the efficacy, side-effect profile and
      relative cost of each product and the following conclusions made: (1) A meta
      analysis of randomized controlled trials comparing the efficacy of intranasal
      corticosteroids and oral antihistamines in the treatment of allergic rhinitis
      showed a clear benefit in favour of intranasal steroids in relieving nasal
      symptoms. (2) There is no clear evidence to support the suggestion that one
      steroid spray is more effective than another in the treatment of seasonal or
      perennial allergic rhinitis. (3) All the sprays have a similar side-effect
      profile; the commonest being epistaxis with a reported incidence between 17 and
      23 per cent. In all the clinical trials, the placebo spray had an appreciable
      rate of epistaxis of between 10 to 15 per cent. (4) Fluticasone causes a
      reduction in endogenous cortisol secretion but no significant adrenal suppression
      was seen with triamcinolone, beclomethasone, budesonide or mometasone. (5) There
      is little evidence that skeletal growth is restricted by the administration of
      topical nasal steroid sprays. (6) There is considerable variation in the daily
      cost of each spray. Beclomethasone, dexamethasone and budesonide are
      significantly cheaper than fluticasone, mometasone or triamcinolone.

PMID- 14670142
TI  - Ni-Ankh-Sekhmet: first rhinologist in history.
AB  - Ni-Ankh-Sekhmet has always been referred to as the first rhinologist in history.
      Translations of the hieroglyphics depicted on all the illustrations accompanying
      previous publications do not substantiate this claim. The research presented is a
      result of an investigation of the original monument related to the doctor at its
      present location in the Egyptian Museum, Cairo. The research proves that Ni-Ankh
      Sekhmet was the first rhinologist in history.

PMID- 14670143
TI  - Delayed loss of residual hearing in Clarion cochlear implant users.
AB  - Hearing threshold has been measured in a group of patients following cochlear
      implantation with a Clarion device for the last eight years. The patients had
      received either a pre-curved carrier or the Hi-Focus I plus Electrode Positioner
      System (EPS). The assessment was carried out within the first post-operative week
      as well as at a later stage, between six and 87 months, post-operatively.
      Residual hearing thresholds were still measurable early after surgery in 24.5 per
      cent of the patients, without differences between the two different Clarion
      models. However, the number of subjects with measurable hearing dropped to 16.3
      per cent as observed when hearing was measured at a later stage, with an equal
      distribution between the two groups of patients. From this study it has been
      possible to observe that only a limited number of patients maintain residual
      hearing after Clarion cochlear implantation, and that this tends to decrease
      further over time. Nevertheless, the performance of these patients for speech
      tests did not appear to be affected by deterioration of the pure-tone auditory
      threshold.

PMID- 14670144
TI  - Alternobaric vertigo in sport SCUBA divers and the risk factors.
AB  - We investigated the eustachian tube function and the incidence of alternobaric
      vertigo (AV) in 29 sport self-contained underwater breathing apparatus (SCUBA)
      divers with, or without, some possible risk factors for AV. The divers had normal
      audiological and otoscopic findings at the pre-dive examination. We used the nine
      step inflation/deflation tympanometric test and Toynbee test for evaluation of
      eustachian tube function, and the Valsalva manoeuvre for patency. Information on
      divers, their history, and their otolaryngologic examination were obtained in the
      pre-dive examination. Divers performed 1086 dives (mean 37, range: 3-100) during
      the observation period. Four divers (14 per cent) experienced AV during five
      dives (0.46 per cent), (one diver experienced AV two times). It was found that
      having an otitis media history or eustachian tube dysfunction determined with the
      nine-step inflation/deflation tympanometric test before diving, or difficulty in
      clearing ears during diving could be important risk factors for AV in sport SCUBA
      divers (p <.05). Divers with such findings seem to be more prone to AV and should
      pay rigorous attention to the precautions for prevention of AV.

PMID- 14670145
TI  - Improving outcomes in rhinocerebral mucormycosis--early diagnostic pointers and
      prognostic factors.
AB  - Rhinocerebral mucormycosis is an uncommon, rapidly progressive, highly fatal
      sinus infection, usually occurring in immunocompromised hosts. We describe our
      clinical experience with nine such consecutive cases managed at our centre, with
      emphasis on identifying early diagnostic and prognostic features. Perinasal
      cellulitis/paraesthesia was the most frequent early clinical sign of disease,
      being evident in at least six cases. Periorbital oedema, mucopurulent rhinorrhoea
      and nasal crusting were the other early manifestations. Concurrent computed
      tomography (CT) scan at this initial stage however revealed only minimal mucosal
      thickening of the sinuses in all four cases wherein it was done. Intracranial
      extension as evident on CT was the only adverse prognostic sign (p<0.05). The
      present report highlights the importance of early diagnosis and prompt
      institution of antifungal chemotherapy in ensuring a favourable outcome in
      rhinocerebral mucormycosis. However, initial CT is frequently near-normal and
      biopsy time-consuming and often not feasible. To optimize early diagnosis
      therefore, the clinician should be highly alert to certain subtle clinical signs,
      in the appropriate setting of an immunocompromised patient.

PMID- 14670146
TI  - Degloving of the inferior turbinates: pilot study to assess the effectiveness of
      a new technique in turbinate reduction.
AB  - A pilot study to assess the safety and efficacy of 'degloving' of the inferior
      turbinate is described. This prospective study reports on the effectiveness of
      the technique in 37 patients with nasal obstruction due to inferior turbinate
      hypertrophy. Both objective and subjective measurements of nasal patency were
      made pre-operatively, and repeated at six weeks, six months and two years post
      operatively using nasal inspiratory peak flow rates, saccharin clearance time and
      an end referenced visual analogue scale to record nasal symptoms. There was a
      significant improvement in the peak inspiratory flow at six weeks (96.4 to 151.2
      l/min) and at six months (148.4 l/min), which was sustained at two years (117.1
      l/min, p<0.001). There was an overall improvement in patient satisfaction with
      nasal symptoms (23.4 to 76.7, 76.8 and 66.8 at six weeks, six months and two
      years, p<0.001) and a decrease in the sensation of nasal obstruction (71.9 to
      21.5, 32.9 and 29.8, p<0.001), which was also sustained. Rhinorrhoea was reduced,
      and sense of smell increased across the group, but the improvements did not reach
      statistical significance. The results for postnasal drip and saccharin clearance
      did not show a significant change over the period of the study. There were no
      haemorrhagic complications in the group studied. This pilot study demonstrates a
      new surgical technique for reduction of the inferior turbinates, that yields
      significant improvement in nasal obstruction, an acceptably low complication rate
      and is well tolerated by patients. A randomized controlled trial is being
      planned.

PMID- 14670147
TI  - Oxidant, vitamin A and angiogenic markers in laryngeal cancer patients.
AB  - In this study the status of oxidant stress, vitamin A and angiotensin-converting
      enzyme (ACE) levels were evaluated in cases of laryngeal carcinoma patients from
      Northern India. In control subjects the levels of malondialdehyde (MDA), vitamin
      A and ACE were 0.23 +/- 0.07 nmole/ml, 2515 +/- 84 IU, and 1.4 +/- 0.8 U/ml
      respectively. Thirty laryngeal cancer patients were divided into three groups
      according to the TNM classification (American Joint Committee on Cancers). In
      laryngeal cancer patients according to tumour size, MDA and ACE levels increased
      to 0.32 +/- 0.04 nmole/ml and 4.7 +/- 0.5 U/ml respectively and the effect was
      statistically significant (p<0.01). The correlation coefficient between different
      subgroups was also highly significant (r=0.96, p<0.01). However, serum vitamin A
      levels decreased to 621 +/- 20 IU and the effect was statistically significant
      (p<0.01). In another two groups of laryngeal cancer patients, a similar pattern
      of various markers was obtained. Thirty patients with laryngeal carcinoma were
      divided into four different groups according to nodal involvement and it was
      observed that in laryngeal cancer patients with no nodal involvement, ACE levels
      were low 3.6 +/- 1.4 U/ml while patients with maximum nodal involvement had the
      highest levels of ACE 7.1 +/- 0.18 U/ml. The correlation coefficient between
      different groups is highly statistically significant (r=0.95, p<0.01). In
      patients with laryngeal cancer the serum MDA and vitamin A levels correlation
      coefficient between different groups was not significant. It is thus concluded
      that serum ACE might be a specific test marker for laryngeal cancer disease
      burden. The use of this marker enzyme for therapeutics is being planned.

PMID- 14670148
TI  - A comparison of survival lifetime of the Provox and the Provox2 voice prosthesis.
AB  - The Provox (Atos Medical AB, Horby, Sweden) voice prosthesis was developed
      between 1988 and 1990 and has been used at our centre with regular success since
      1993. Since 1996, a second generation of Provox (Provox2) has been used, which
      can be inserted by an anterograde technique. The aim of this study is to compare
      the survival lifetime of both voice prostheses. The survival time of the two
      voice prostheses were compared retrospectively in 152 devices placed in 38
      patients. A Kaplan-Meier analysis was performed to determine the survival
      lifetimes and a log rank test was performed to compare the two curves. Clinical
      factors affecting the lifetime were also analysed with a Kaplan-Meier plot. The
      median survival lifetime of the Provox and Provox2 were 303 and 144 days
      respectively. The Kaplan-Meier estimation shows that this difference is
      statistically significant (p=0.02). It is considered an early failure if it
      occurs within the first three months. There was a larger number of early failures
      with the Provox2 than with the Provox (p=0.04). Neither the gender nor the age
      affected the lifetime of the devices. Radiotherapy seemed to lengthen the
      lifetime of the first valve. The survival lifetime of the second generation
      Provox2 valve is shorter than the lifetime of the first generation Provox. This
      could be due to the difference in elasticity of these valves that could lead to a
      different level of colonization and invasion of the valves by micro-organisms.

PMID- 14670149
TI  - Use of audiotaped patient consultations in a head and neck oncology clinic and
      survey of patient attitudes to this facility.
AB  - The overall quality and delivery of patient care is becoming increasingly
      important, especially in those diagnosed with cancer. Multidisciplinary clinics
      are a valuable adjunct to this, but patients may not fully understand or
      comprehend all that is said to them. The use of audiotaping consultations has
      been studied in some settings, but not in head and neck cancer clinics. We report
      on a series of 50 consecutive head and neck patients to determine their views on
      the value of this facility. Thirty-nine patients (78 per cent) utilized the
      opportunity, of which 36 patients (92 per cent) found it beneficial. Over three
      quarters of the patients who used the facility thought that medical staff could
      benefit and learn from the tape recording. We recommend that audiotaping becomes
      a standard part of the multidisciplinary head and neck oncology clinic, helping
      to improve the overall quality of patient care.

PMID- 14670150
TI  - A novel method for replacement of a blocked fine bore nasogastric tube.
AB  - Nasogastric intubation is often difficult in patients with upper aero-digestive
      tract tumours. We present a new method for replacing obstructed fine-bore
      nasogastric tubes. This method eliminates the need for specialized equipment and
      skills, minimizes the risk of tracheal intubation and oesophageal trauma, and is
      better tolerated by patients.

PMID- 14670151
TI  - Mucous membrane pemphigoid: nasal and laryngeal manifestations.
AB  - Mucous membrane pemphigoid (MMP) is a sub-epithelial blistering disease that
      primarily involves mucosal surfaces but may also involve the skin. Clinically, it
      appears as vesiculobullous lesions of the oral cavity and eyes, but other tissues
      such as the nasopharyngeal and laryngeal mucosa can also be affected. Ultimately,
      scarring and airway stenosis may occur. The condition should be managed by a
      multidisciplinary team led by a dermatologist. Immunosuppressive therapy forms
      the mainstay of treatment, with surgery having both a diagnostic role and a use
      in the treatment of complications such as airway obstruction. There must be a low
      threshold of suspicion for laryngeal involvement in this group of patients, so
      that prompt action can be taken. Once laryngeal stenosis has occurred repeated
      endoscopic laser excision of scar tissue can be used to maintain an adequate
      airway. Adjuvant use of mitomycin-C can be used beneficially in the treatment of
      laryngeal complications of MMP.

PMID- 14670152
TI  - Endoscopic treatment of an ethmoidal solitary fibrous tumour.
AB  - Solitary fibrous tumours are rare neoplasms, which occur most frequently during
      adulthood at the level of the pleura. Recently, these tumours have been
      demonstrated in extraserosal sites such as the nasal cavity. A case of a solitary
      fibrous tumour arising at the level of the ethmoid and presenting in a 54-year
      old woman, is reported. The tumour was removed using an endonasal endoscopic
      approach that permitted the monobloc excision of the lesion. The patient is
      without evidence of disease 18 months after surgery.

PMID- 14670153
TI  - Orbitofrontal cholesterol granuloma: percutaneous endoscopic-assisted curettage.
AB  - This paper describes the use of endoscopic visualization in curettage of orbital
      cholesterol granuloma (OCG). Two males aged 54 and 50 years presented with
      orbitofrontal cholesterol granulomas arising in the superolateral frontal bone
      and abutting the dura. The granulomas were approached via a superior eyelid
      crease incision and a 70 degree rigid endoscope was used to visualize curettage
      of the granuloma from the inner surface of the frontal bone and the dura. Both
      patients made an uncomplicated recovery and there was no recurrence at eight
      months and two years follow up. Percutaneous endoscopic curettage is an
      alternative to blind curettage, lateral orbitotomy or frontal craniotomy for OCG.

PMID- 14670154
TI  - Agenesis of the epiglottis and false vocal folds with maxillary hypoplasia in an
      adult.
AB  - Hypoplasia or absence of the epiglottis in an adult is a rarely reported
      congenital anomaly that usually occurs in association with congenital anomalies
      of other organ systems. Most epiglottic anomalies usually present in infancy and
      early childhood with respiratory and feeding problems and the affected individual
      dies shortly after birth due to multiple congenital anomalies. We present a case
      of congenital absence of the epiglottis and false vocal folds with hypoplastic
      maxillae in an adult.

PMID- 14670155
TI  - Massive subcutaneous emphysema following routine endotracheal intubation.
AB  - Upper aerodigestive tract injury after endotracheal intubation is a rare but
      serious complication. The case of a 57-year-old female, who developed extensive
      neck and pneumomediastinum following a knee arthroscopy under general
      anaesthesia, is presented. Possible mechanisms of injury and management options
      are discussed.

PMID- 14670156
TI  - Removal of sub-mucosal foreign body (metal wire) from the pharynx using image
      intensifier.
AB  - It is well known how difficult it is to localize a foreign body in the sub
      mucosal tissues. This is a report of a male who swallowed a metal wire which
      lodged in the pharyngeal sub-mucosal tissue. The foreign body was localized using
      an image intensifier and removed successfully.

PMID- 14670157
TI  - Sialolithiasis in the sublingual gland.
AB  - Sialolithiasis is a major cause of salivary gland dysfunction. The submandibular
      gland is the most common site followed by the parotid gland. The sublingual gland
      and minor glands are very rare sites for stone formation. This paper describes a
      case of multiple sialoliths arising in the sublingual gland. They presented on
      the right floor of the mouth. The sublingual gland and sialoliths were completely
      removed with careful preservation of the lingual nerve and Wharton's duct. This
      was an uncommon sialolithiasis of the sublingual gland in a 14-year-old female.

PMID- 14670158
TI  - Magnetic resonance imaging of pleomorphic adenoma arising from the external
      auditory canal.
AB  - Pleomorphic adenoma arising from the external auditory canal is a very rare
      neoplasm, and there has been no report on magnetic resonance (MR) imaging of
      pleomorphic adenoma of the external auditory canal. We report here a case of 65
      year-old male with this tumour, measuring 12 mm in a diameter. Histopathology was
      confirmed from the specimen obtained at the surgical excision. MR revealed that
      the tumour had a well-defined margin showing hypointensity on T1-weighted images
      and hyperintensity on T2-weighted images relative to the parotid gland. The
      tumour was well enhanced by contrast material. No invasion to the surrounding
      tissue was observed. These MR findings were compatible with pleomorphic adenoma
      of the salivary gland origin. In treating pleomorphic adenoma of the external
      auditory canal, complete surgical excision is essential for the prevention of
      recurrence. It can be concluded that MR imaging is helpful for making a
      differential diagnosis of external auditory canal tumours and selection of
      adequate treatment.

PMID- 14670162
TI  - The evolution of a National Public Health Initiative on Diabetes and Women's
      Health: a model process.
AB  - Diabetes is a serious chronic disease that affects women in all life stages, from
      adolescence to the older years. Diabetes also imposes a significant economic
      burden on individuals, families, and society. The National Public Health
      Initiative on Diabetes and Women's Health was formed to guide the nation in
      addressing diabetes and women's health issues. This paper documents the rationale
      for developing an initiative on diabetes and women's health and the processes
      used to implement it.

PMID- 14670163
TI  - Toward optimal health: the experts discuss the use of botanicals by women.
      Interview by Jody Godfrey Meisler.

PMID- 14670164
TI  - Estrogen and thromboembolic disorders: should patients stop hormones prior to
      cosmetic surgery?
AB  - Oral contraceptives and replacement estrogenic hormones have been associated with
      a significant risk of thromboembolism. Cosmetic surgery consists of elective
      procedures in otherwise healthy individuals. The prospect of thromboembolism
      should be diminished in these patients by avoiding those factors that may give
      rise to the problem. Stopping oral contraceptives and replacement estrogens three
      weeks before surgery to two weeks after surgery is not difficult for most
      patients and should be part of the custom and practice of all cosmetic surgeons.

PMID- 14670165
TI  - Conference report: complex clinical, legal, and ethical issues of pregnant and
      postpartum women as subjects in clinical trials.
AB  - BACKGROUND: The Office of the Vice President for Research and School of Nursing
      of the University of Texas Medical Branch convened a multidisciplinary conference
      to address the national problem of underrepresentation of pregnant women in
      clinical trials. METHODS: Conference participants reviewed pertinent issues
      through lectures and panel discussions. RESULTS: More funded studies are needed
      to specifically examine pharmacokinetic, physiological, and pharmacological
      interactions in the pregnant woman. Legal, ethical, and financial issues need to
      be better delineated, and more focus is needed on specific diseases with
      particular import for pregnant women and their fetuses. CONCLUSIONS: This paper
      provides a report on the conference and the powerful consensus statements
      developed by the participants.

PMID- 14670166
TI  - Development of a comprehensive women's health program in an academic medical
      center: experiences of the Indiana University National Center of Excellence in
      Women's Health.
AB  - BACKGROUND: The IU National Cancer of Excellence (CoE) in Women's Health was
      funded by the Office on Women's Health, Department of Health and Human Services,
      in 1997 as part of the "second generation" of CoEs. The purpose of this paper is
      to describe the changes that the existence of this Center have wrought within the
      IU School of Medicine. METHODS: This paper describes the creation, mission, and
      function of the IU CoE, as well as some of its accomplishments to date. RESULTS:
      Through its missions targeting clinical care, research, education, community
      outreach, and leadership development, the IU CoE has significantly changed the
      delivery of care to and by women at this institution. CONCLUSIONS: The IU CoE has
      been responsible for major changes in the concepts of women's health from a
      clinical, research, education, and leadership perspective at the IU School of
      Medicine. Similar cases can be made for most of the other CoEs around the
      country. The challenges being faced continue to be sustained and sufficient
      funding for these valuable Centers.

PMID- 14670167
TI  - Sacral stress fractures.
AB  - Stress fractures result from skeletal failure resulting from submaximal
      repetitive forces over time. Sacral stress fractures may represent an
      underdiagnosed cause of low back and buttock pain. They occur primarily in two
      populations, young active persons and elderly osteoporotic women, usually
      corresponding to fatigue and insufficiency-type fractures, respectively. The
      clinical presentation of these fractures is similar, but the medical and
      rehabilitation management of these patient populations differs and is tailored to
      the specific underlying etiology. In both types of fractures, appropriate
      conservative measures generally result in good functional outcomes. This paper
      provides an overview of the anatomical considerations, risk factors, clinical
      presentations, diagnostic imaging findings, appropriate laboratory studies,
      medical management, and rehabilitation management of patients with sacral stress
      fractures.

PMID- 14670168
TI  - The challenges of informed consent for rapid HIV testing in labor.
AB  - BACKGROUND: Although increasing attention has been focused on the adequacy of the
      informed consent process for participation in research studies, there has been
      little systematic evaluation of the process, particularly when consent is
      obtained in the labor and delivery setting. The Mother Infant Rapid Intervention
      at Delivery (MIRIAD) study is an ongoing multisite study initiated by the Centers
      for Disease Control and Prevention (CDC) designed to evaluate the feasibility of
      offering 24-hour counseling and voluntary rapid HIV testing and antriretroviral
      therapy when indicated to women with unknown HIV status who are in labor.
      METHODS: To address concerns about obtaining informed consent from women in
      labor, we have completed focus groups, conducted a pilot of the informed consent
      process among women in labor, developed flip-charts to enhance comprehension, and
      plan an ongoing evaluation of the informed consent process throughout the course
      of the MIRIAD study. RESULTS: In the pilot study, approximately 70% of women were
      able to state in their own words the purpose and benefits of the research study.
      Substantially fewer women (25%) were able to state one or more risks of the
      study. CONCLUSIONS: We hope that the MIRIAD study will make a valuable
      contribution by defining best approaches for informed consent and will provide
      guidance when it is necessary to obtain consent from laboring women for crucial
      interventions.

PMID- 14670169
TI  - Medical treatment of women and adherence to HIV guidelines at an urban university
      staffed public clinic.
AB  - BACKGROUND: HIV-related morbidity and mortality have declined in recent years in
      the United States. Relative to their male counterparts, however, HIV-infected
      women tend to have less reduced morbidity and mortality. The purpose of this
      study was to investigate if the reported small decreases in HIV-related morbidity
      and mortality in women could be due to their receiving a lesser standard of care
      from public health clinics. METHODS: One hundred sixteen female and 131 male
      patients who were diagnosed with HIV infection were drawn consecutively from a
      county-owned health clinical database in Houston, Texas. Physicians from the two
      local medical schools staffed the clinic. Information on patients' demographic
      characteristics, screening tests, clinical care, and prophylaxis care was
      abstracted for comparison. RESULTS AND CONCLUSIONS: The data showed that there
      were no statistically significant sex-based differences in getting access to
      antiretroviral treatment or for prophylaxis of opportunistic infections in the
      clinic. Sex-based differences, however, were found in the initial CD4 cell count
      and HIV load. Women had higher CD4 cell counts and HIV RNA levels at the initial
      stage and during the time of treatment.

PMID- 14670170
TI  - Antibiotic use and preterm labor: attitudes and practice patterns of North
      Carolina obstetric providers.
AB  - BACKGROUND: Despite the reported link between subclinical genital tract infection
      (GTI) and preterm labor (PTL), it is not certain that treating PTL empirically
      with antibiotics decreases neonatal morbidity and mortality. This study describes
      the beliefs of family physicians and nurse-midwives regarding the link between
      subclinical GTI and PTL and their use of empiric antibiotics to treat spontaneous
      PTL. METHODS: This was a survey of family physicians, family practice residents,
      and midwives (n = 588) who practice obstetrics in North Carolina. The response
      rate was 61%. RESULTS: Ninety-six percent of providers search for GTI, and 76%
      believe antibiotics for presumed infection will benefit the neonate. Wide
      variation in the use of antibiotics exists within groups and between groups of
      providers. Nurse-midwives are more likely than family physicians to use broad
      spectrum antibiotics (p < 0.001). CONCLUSIONS: Family physicians and nurse
      midwives are uncertain about the optimal management of PTL. Empiric antibiotic
      use varies widely despite the lack of supportive data.

PMID- 14670171
TI  - Health status among women with menstrual symptoms.
AB  - PURPOSE: Chronic diseases have been associated with decrements in health status,
      as measured by the Medical Outcomes Study's Short Form-36 (SF-36). Menstrual
      symptoms (including irregular menses, menorrhagia, dysmenorrhea and premenstrual
      symptoms) are common, but little is known about their impact on health status. We
      sought to determine the prevalence of menstrual symptoms and the degree to which
      these symptoms affect health status. METHODS: This was a mailed survey including
      questions about sociodemographic characteristics, military experiences, current
      physical symptoms and medical conditions, mental health, health status (SF-36),
      and life experiences. The participants were a nationally representative, randomly
      selected sample of women veterans who had made at least one ambulatory visit to a
      Veterans Affairs facility between July 1, 1994 and June 30, 1995. The main
      outcome measures were eight domains of the SF-36 health status questionnaire.
      RESULTS: Among 3632 respondents (58.4% response rate), 1744 were menstruating
      women and formed the analytical sample for this study. Among these women (mean
      age 35.8), 67% reported one or more menstrual symptoms. Women with menstrual
      symptoms had significantly lower scores for all domains of the SF-36 (p < 0.01),
      except energy and vitality (p < 0.05), both before and after adjusting for
      sociodemographic, psychosocial, and comorbidity variables. CONCLUSIONS: Women
      veterans who report one or more menstrual symptoms have significantly lower
      health status compared with those reporting none. Clinicians providing care for
      women should be attuned to the potential impact of menstrual symptoms on the
      lives of their patients.

PMID- 14670172
TI  - Factors associated with arm swelling after breast cancer surgery.
AB  - PURPOSE: As life expectancy improves for women with breast cancer, more women
      will be living with symptoms of lymphedema. This study reports the incidence of
      arm or hand swelling and associated risk factors in women with invasive breast
      cancer following surgery. METHODS: Data were obtained from baseline and follow-up
      interviews of women with invasive breast cancer (n = 145), and mammography and
      pathology records. The Kaplan-Meier method was used to estimate the probability
      of developing arm or hand swelling over time. Univariate and multivariate
      logistic regression analyses were conducted to identify risk factors for arm or
      hand swelling. RESULTS: Of women in this study, 38% self-reported arm or hand
      swelling. There was a significantly increased risk of arm swelling if women were
      under 50 years of age, had axillary node dissection, received chemotherapy,
      worked outside the home, and had a high household income. There was no
      association of body weight with swelling. A significantly decreased risk of arm
      swelling was found in women who were on treatment for high blood pressure. After
      adjustment for nodal dissection, only age had a significant independent effect.
      CONCLUSIONS: Our study highlights two important areas of future research that
      could reduce the incidence of lymphedema. There is a need to better understand
      the role that treatment for high blood pressure may play in protecting women from
      arm edema. Second, the potential effect of weight as a modifiable lymphedema risk
      factor needs to be studied in more detail in light of the conflicting results of
      different studies.

PMID- 14670173
TI  - Medical device surveillance: gender differences in pulmonary artery rupture after
      pulmonary artery catheterization.
AB  - BACKGROUND: Pulmonary artery (PA) rupture is a rare but often fatal complication
      of PA catheterization. METHODS: An analysis was performed of all the case reports
      of PA rupture after PA catheterization that were submitted to the Food and Drug
      Administration's Medical Device Reporting (MDR) system between the years 1991 and
      2001. The MDR system is a national passive surveillance system that includes
      adverse event reports from such sources as manufacturers and healthcare
      professionals. The Nationwide Inpatient Sample (NIS), a massive, nationally
      representative database maintained by the Agency for Healthcare Research and
      Quality, was examined to study patterns of PA catheter use. RESULTS: A total of
      71 PA rupture cases were identified from the MDR data. The most likely outcome
      following PA rupture was death. These PA ruptures were associated with 47 deaths
      and 24 injuries. The range of reported ages of the cases was between 40 and 91
      years, with a mean age of 74 years. Of the 71 PA rupture cases, 52 were in women
      and 10 were in men, with gender not reported in 9 of the cases. There were
      significantly more cases in women than expected (Mantel-Haenszel common odds
      ratio estimate = 5.84, 95% confidence interval = 2.97 - 11.46, p < 0.001).
      CONCLUSIONS: These data suggest that women may be at significantly greater risk
      of PA rupture after PA catheterization than men. Clinicians must be aware of the
      potential for this complication of PA catheterization.

PMID- 14670175
TI  - Ultrasound-guided optical tomographic imaging of malignant and benign breast
      lesions: initial clinical results of 19 cases.
AB  - The diagnosis of solid benign and malignant tumors presents a unique challenge to
      all noninvasive imaging modalities. Ultrasound is used in conjunction with
      mammography to differentiate simple cysts from solid lesions. However, the
      overlapping appearances of benign and malignant lesions make ultrasound less
      useful in differentiating solid lesions, resulting in a large number of benign
      biopsies. Optical tomography using near-infrared diffused light has great
      potential for imaging functional parameters of 1) tumor hemoglobin concentration,
      2) oxygen saturation, and 3) metabolism, as well as other tumor distinguishing
      characteristics. These parameters can differentiate benign from malignant
      lesions. However, optical tomography, when used alone, suffers from low spatial
      resolution and target localization uncertainty due to intensive light scattering.
      Our aim is to combine diffused light imaging with ultrasound in a novel way for
      the detection and diagnosis of solid lesions. Initial findings of two early-stage
      invasive carcinomas, one combined fibroadenoma and fibrocystic change with
      scattered foci of lobular neoplasia/lobular carcinoma in situ, and 16 benign
      lesions are reported in this paper. The invasive cancer cases reveal about two
      fold greater total hemoglobin concentration (mean 119 micromol) than benign cases
      (mean 67 micromol), and suggest that the discrimination of benign and malignant
      breast lesions might be enhanced by this type of achievable optical
      quantification with ultrasound localization. Furthermore, the small invasive
      cancers are well localized and have wavelength-dependent appearance in optical
      absorption maps, whereas the benign lesions appear diffused and relatively
      wavelength-independent.

PMID- 14670176
TI  - SMAD5 gene expression, rearrangements, copy number, and amplification at fragile
      site FRA5C in human hepatocellular carcinoma.
AB  - Signaling by the transforming growth factor (TGF)-family members is transduced
      from the cell surface to the nucleus by the Smad group of intracellular proteins.
      Because we detected alterations on the long arm of chromosome 5, we examined the
      status of the SMAD5 gene in human hepatocellular carcinoma (HCC) cell lines and
      primary HCC. In 16 cell lines, chromosome alterations of chromosome 5 were
      observed in nine cell lines by fluorescence in situ hybridization (FISH), and an
      increase in SMAD5 gene copy number relative to the ploidy level was found in
      eight lines. The breakpoints in unbalanced translocations and deletions
      frequently occurred near the SMAD5 locus, but apparently did not cause loss of
      SMAD5. In one cell line, where comparative genomic hybridization showed DNA copy
      number gain confined to the region 5q31, we detected by FISH high-level
      amplification of the SMAD5 gene located within the fragile site FRA5C.
      Semiquantitative polymerase chain reaction did not reveal changes in SMAD5 DNA
      levels in 15 of 17 primary HCC specimens. In 17 HCC cell lines, SMAD5 mRNA levels
      were either maintained or upregulated by an increase in gene dosage or another
      mechanism. Collectively, our results show that SMAD5 undergoes copy number gain
      and increased expression, rather than loss of expression, and therefore suggest
      that this gene does not act as a tumor-suppressor gene in HCC. The Hep-40 HCC
      cell line with high-level amplification and significant overexpression of SMAD5
      may be useful in studying the interaction of SMAD5 with other genes.

PMID- 14670177
TI  - Candidate genes for testicular cancer evaluated by in situ protein expression
      analyses on tissue microarrays.
AB  - By the use of high-throughput molecular technologies, the number of genes and
      proteins potentially relevant to testicular germ cell tumor (TGCT) and other
      diseases will increase rapidly. In a recent transcriptional profiling, we
      demonstrated the overexpression of GRB7 and JUP in TGCTs, and confirmed the
      reported overexpression of CCND2. We also have recent evidences for frequent
      genetic alterations of FHIT and epigenetic alterations of MGMT. To evaluate
      whether the expression of these genes is related to any clinicopathological
      variables, we constructed a tissue microarray with 510 testicular tissue cores
      from 279 patients diagnosed with TGCT, covering various histological subgroups
      and clinical stages. By immunohistochemistry, we found that JUP, GRB7, and CCND2
      proteins were rarely present in normal testis, but frequently expressed at high
      levels in TGCT. Additionally, all premalignant intrabular germ cell neoplasias
      were JUP-immunopositive. MGMT and FHIT were expressed by normal testicular
      tissues, but at significantly lower frequencies in TGCT. Except for CCND2, the
      expressions of all markers were significantly associated with various TGCT
      subtypes. In summary, we have developed a high-throughput tool for the evaluation
      of TGCT markers, and utilized this to validate five candidate genes whose protein
      expressions were indeed deregulated in TGCT.

PMID- 14670178
TI  - Degradation and dephosphorylation of focal adhesion kinase during okadaic acid
      induced apoptosis in human neuroblastoma cells.
AB  - Focal adhesion kinase (FAK) prevents apoptosis in many cell types. We have
      reported that tyrosine residues in FAK are dephosphorylated and FAK is degraded
      during mannitol-induced apoptosis in human neuroblastoma cells. Several studies
      suggest that FAK dephosphorylation and degradation are separate events. The
      current study defines the relationship between FAK dephosphorylation and
      degradation in neuroblastoma cells using okadaic acid (OA). OA, a serine
      phosphatase inhibitor, promotes serine/threonine phosphorylation, which in turn
      blocks tyrosine phosphorylation. OA induced focal adhesion loss, actin
      cytoskeleton disorganization, and cellular detachment, which corresponded to a
      loss of FAK Tyr397 phosphorylation. These changes preceded caspase-3 activation,
      Akt and MAP kinase activity loss, protein ubiquitination, and cellular apoptosis.
      Insulin-like growth factor-I prevented mannitol-induced, but not OA-induced,
      substrate detachment and FAK Tyr397 dephosphorylation, and the effects of OA on
      FAK Tyr397 phosphorylation were irreversible. The proteolytic degradation of FAK
      is temporally distinct from its tyrosine dephosphorylation, occurring when
      apoptotic pathways are already initiated and during a generalized destruction of
      signaling proteins. Therefore, agents resulting in the dephosphorylation of FAK
      may be beneficial for therapeutic treatment, irrespective of FAK protein levels,
      as this may result in apoptosis, which cannot be prevented by growth factor
      signaling.

PMID- 14670179
TI  - 2-Methoxyestradiol exhibits a biphasic effect on VEGF-A in tumor cells and
      upregulation is mediated through ER-alpha: a possible signaling pathway
      associated with the impact of 2-ME2 on proliferative cells.
AB  - 2-Methoxyestradiol (2-ME2) was reported to elicit both stimulation and inhibition
      of tumor angiogenesis and growth depending on the dosage used. However, the
      mechanism(s) of the biphasic action of 2-ME2 has been elusive. Here we describe a
      regulatory role of vascular endothelial growth factor-A (VEGF-A) in the biphasic
      effects on estrogen receptor (ER)+ GH3 rat pituitary tumor cells and MCF-7 human
      breast tumor cells depending on the dosage of 2-ME2 used. We observed that acute
      exposure to 2-ME2, irrespective of dosage, did not alter cellular proliferation,
      but enhanced the VEGF-A mRNA level. As the treatment duration increased, biphasic
      effect was elicited. A concentration of 1 microM 2-ME2 increased both cell
      proliferation and VEGF-A levels in these cells, whereas higher doses exhibited
      reversed impact. A low dose of 2-ME2 also increased the VEGF-A mRNA expression in
      ER-alpha-transfected human mammary epithelial cells (HMECs). The effect was
      reversed in ER- cells. The enhanced expression of VEGF-A mRNA could be blocked by
      the pure estrogen antagonist, ICI 182,780, and reveal that the upregulation of
      VEGF-A expression by 2-ME2 is mediated through ER-alpha. Furthermore, the
      biphasic effect of 2-ME2 on cell proliferation can be modulated by administrating
      VEGF-A antibodies or VEGF-A proteins. Studies also demonstrate that the VEGF-A
      protein, induced by 2-ME2, is functionally active and upregulates the
      proliferation of adjacent endothelial cells.

PMID- 14670181
TI  - Isolation of a colon tumor specific binding peptide using phage display
      selection.
AB  - Colorectal cancer is the third most common malignancy in the United States.
      Improved detection sensitivity of early colorectal neoplasms would have important
      clinical applications. Herein, we report on using phage display to generate
      peptide libraries that detect colon carcinoma tissues. To accomplish this, we
      employed positive selection of a peptide-bearing phage library on poorly
      differentiated colon carcinoma cells (HT29) and combined this with negative
      selection of the phage library on well-differentiated colon carcinoma cells
      (HCT116). Analysis of the resulting library identified a nine-amino-acid,
      disulfide-constrained peptide, CPIEDRPMC (RPMrel), that stained HT29 colon
      carcinoma cells. Immunohistochemical staining using FITC-conjugated RPMrel
      peptide also showed binding of RPMrel to colon tumor tissues from four patients.
      We saw no binding of RPMrel to normal colon tissues. In addition, RPMrel failed
      to stain a panel of noncolon tissues including the lungs, liver, and stomach. We
      further demonstrated that RPMrel coupled to the mitochondrial toxin (KLAKLAK)2
      killed HT29 cells. These studies suggest that RPMrel may be a promising lead
      candidate in the development of a useful colon tumor diagnostic and targeted drug
      delivery agent.

PMID- 14670180
TI  - Human pancreatic carcinoma cells activate maspin expression through loss of
      epigenetic control.
AB  - The maspin gene is not expressed in normal human pancreas, but its expression is
      acquired during human pancreatic carcinogenesis. In other normal human cells and
      their malignant counterparts, maspin expression is controlled through the
      epigenetic state of its promoter. In studies presented herein, we used bisulfite
      genomic sequencing and chromatin immunoprecipitation studies to show that maspin
      negative pancreas cells have a methylated maspin promoter, and that the
      associated H3 and H4 histones are hypoacetylated. In contrast to normal pancreas,
      four of six human pancreatic carcinoma cell lines investigated displayed
      activation of maspin expression. This activation of maspin expression in
      pancreatic carcinoma cells was linked to demethylated promoters and
      hyperacetylation of the associated H3 and H4 histones. In addition, 5-aza-2'
      deoxycytidine treatments activated maspin expression in the two maspin-negative
      pancreatic carcinoma cell lines, suggesting a causal role for cytosine
      methylation in the maintenance of a transcriptionally silent maspin gene. Thus,
      human pancreatic carcinoma cells acquire maspin expression through epigenetic
      derepression of the maspin locus, and in so doing appear to co-opt a normal
      cellular mechanism for the regulation of this gene.

PMID- 14670182
TI  - Inhibition of VEGF-dependent multistage carcinogenesis by soluble EphA receptors.
AB  - Elevated expression of Eph receptors has long been correlated with the growth of
      solid tumors. However, the functional role of this family of receptor tyrosine
      kinases in carcinogenesis and tumor angiogenesis has not been well characterized.
      Here we report that soluble EphA receptors inhibit tumor angiogenesis and tumor
      progression in vivo in the RIP-Tag transgenic model of vascular endothelial
      growth factor (VEGF)-dependent multistage pancreatic islet cell carcinoma.
      Soluble EphA receptors delivered either by a transgene or an osmotic minipump
      inhibited the formation of angiogenic islet, a premalignant lesion, and reduced
      tumor volume of solid islet cell carcinoma. EphA2-Fc or EphA3-Fc treatment
      resulted in decreased tumor volume but increased tumor and endothelial cell
      apoptosis in vivo. In addition, soluble EphA receptors inhibited VEGF and betaTC
      tumor cell-conditioned medium-induced endothelial cell migration in vitro and
      VEGF-induced cornea angiogenesis in vivo. A dominant negative EphA2 mutant
      inhibited--whereas a gain-of-function EphA2 mutant enhanced--tumor cell-induced
      endothelial cell migration, suggesting that EphA2 receptor activation is required
      for tumor cell-endothelial cell interaction. These data provide functional
      evidence for EphA class receptor regulation of VEGF-dependent tumor angiogenesis,
      suggesting that the EphA signaling pathway may represent an attractive novel
      target for antiangiogenic therapy in cancer.

PMID- 14670184
TI  - Squamous cell lung cancer presenting as a malar mass.
AB  - INTRODUCTION: Lung cancer metastasizing to the face has rarely been reported and
      is an even more unusual presentation. CASE: This is the case of a 49-year-old man
      diagnosed with squamous cell carcinoma of the face, scheduled for resection.
      Preoperative radiographs revealed a left upper lobe mass, found to be squamous
      cell carcinoma. Diagnosis was changed to Stage IV primary lung cancer. The
      patient did not undergo resection. DISCUSSION: No previous cases of primary lung
      cancer presenting as a malar mass have been reported. Facial lesions can be the
      presenting feature of primary lung cancer. Discovery of the true primary lesion
      can alter therapy and prognosis.

PMID- 14670185
TI  - Interpersonal profiles in eating disorders: ratings of SASB self-image.
AB  - INTRODUCTION: Although evidence suggests that interpersonal psychotherapy may be
      an efficacious treatment for eating disorders, there is surprisingly little
      systematic knowledge about the interpersonal world of these patients. METHOD:
      SASB self-image ratings were used to explore interpersonal profiles in a large
      heterogeneous sample of eating disorders (N = 830), matched normal controls (N =
      105) and a small group of controls with subclinical depression (N = 26). RESULTS:
      Eating disorder patients clearly presented with significantly more negative
      interpersonal profiles compared to controls. Within the eating disorder group,
      anorexics were characterized by high self-control, self-blame and self-attack.
      Patients with binge eating disorder expressed the least negative self-image, and
      were significantly more self-affirming than bulimics and less self-controlling
      than patients with atypical eating disorders. CONCLUSIONS: Eating disorder
      patients may have distinct interpersonal profiles that increase the risk of
      negative therapeutic reaction. Better knowledge of interpersonal processes in
      eating disorders may help to improve both diagnostic assessment and treatment.

PMID- 14670186
TI  - The relationship between attachment strategies and psychopathology in
      adolescence.
AB  - AIM: The majority of research investigating attachment and psychopathology has
      focused largely on children, and more recently adults. By comparison, few studies
      have considered the role of attachment on the development of psychopathology
      during adolescence. The scarcity of studies in this area is surprising given that
      adolescence is a critical period of psychological adjustment. This study
      investigates attachment patterns in adolescence and their relationship to
      symptomatology and interpersonal difficulties. METHOD: A two-sample comparative
      design was employed so that a clinical group of adolescents were compared with a
      matched non-clinical group, on attachment classifications (using a modified
      Separation Anxiety Test), reported interpersonal difficulties and clinical
      symptoms. RESULTS: Significant differences were found between the clinical and
      non-clinical groups on attachment classifications. Adolescents with ambivalent
      attachment patterns reported significantly more interpersonal difficulties and
      symptoms compared to young people classified as having secure and avoidant
      attachment classifications. The results are suggestive of specific differences in
      the way difficulties are reported. CONCLUSION: The findings are consistent with
      two strategies of affect regulation. It is proposed that a 'hyperactivating'
      strategy and a 'deactivating' strategy may be operating among those adolescents
      with ambivalent and avoidant attachment classifications, respectively. The
      implications of using self-report measures in clinical work and for evidence
      based practice are discussed.

PMID- 14670187
TI  - Interpersonal relating and voice hearing: to what extent does relating to the
      voice reflect social relating?
AB  - The experience of hearing voices (auditory hallucinations) has been construed as
      that of relating to an interpersonal 'other'. This preliminary study utilized
      Birtchnell's (1996, 2002) theory of relating to investigate the hypothesis that
      people who hear voices relate to the voices and to people within their social
      environment in similar ways. A correlational design was adopted and 27 people
      provided information about the characteristics of their voice-hearing experience,
      relating to the voice and relating socially. Significant correlations were found
      between relating to the voice and relating socially in terms of the 'dominant'
      and 'submissive' forms of power and the 'clinging' form of proximity: these
      associations were independent of beliefs about the voices and mood-linked
      appraisals. However, relating from a position of 'withdrawal' was found to be
      unique to the experience of voice hearing, and was most extreme when relating to
      voices that were perceived to have no identity. This study offers further
      evidence in support of the hypothesis that people who hear voices relate to them
      in ways that reflect more pervasive patterns of social relating. The clinical
      implications of these findings for assessment and intervention are discussed.

PMID- 14670183
TI  - TRAIL activates a caspase 9/7-dependent pathway in caspase 8/10-defective SK-N-SH
      neuroblastoma cells with two functional end points: induction of apoptosis and
      PGE2 release.
AB  - Most neuroblastoma cell lines do not express apical caspases 8 and 10, which play
      a key role in mediating tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) cytotoxicity in a variety of malignant cell types. In this study, we
      demonstrated that TRAIL induced a moderate but significant increase of apoptosis
      in the caspase 8/10-deficient SK-N-SH neuroblastoma cell line, through activation
      of a novel caspase 9/7 pathway. Concomitant to the induction of apoptosis, TRAIL
      also promoted a significant increase of prostaglandin E2 (PGE2) release by SK-N
      SH cells. Moreover, coadministration of TRAIL plus indomethacin, a
      pharmacological inhibitor of cyclooxygenase (COX), showed an additive effect on
      SK-N-SH cell death. In spite of the ability of TRAIL to promote the
      phosphorylation of both ERK1/2 and p38/MAPK, which have been involved in the
      control of COX expression/activity, neither PD98059 nor SB203580, pharmacological
      inhibitors of the ERK1/2 and p38/MAPK pathways, respectively, affected either
      PGE2 production or apoptosis induced by TRAIL. Finally, both induction of
      apoptosis and PGE2 release were completely abrogated by the broad caspase
      inhibitor z-VAD-fmk, suggesting that both biologic end points were regulated in
      SK-N-SH cells through a caspase 9/7-dependent pathway.

PMID- 14670188
TI  - Dialogical relationships in impoverished narratives: from theory to clinical
      practice.
AB  - Individuals are guided in their actions in the world by a set of narratives
      portraying them in their relations with others. The narratives contain
      representations of self, of the world, of the various characters with which
      individuals interact and of the forms of relationship that they foresee
      establishing. Within the narratives the various characters, each from the
      position of an independent author, negotiate the meaning of events. A narrative
      can be altered either as regards its contents or its form. In this article, we
      describe impoverished narratives. These are lacking in various elements
      descriptions of a narrator's inner state, of others' points of view, of the
      action scenario and of what goes on between the characters-and concentrate
      repetitively on only one or a few themes. With such features, individuals are
      hampered in their actions in the world. A therapist listening to a patient
      relating impoverished narratives finds it difficult to grasp what the problems
      are and what steps need to be taken. As a result, it takes longer or is not
      possible for each to become attuned with the other and to put together an agreed
      treatment programme. We illustrate this narrative deficit with a psychotherapy
      case study and hypothesize about the way a therapist ought to operate in order to
      tackle the deficit.

PMID- 14670189
TI  - Living with puerperal psychosis: a qualitative analysis.
AB  - OBJECTIVES: To explore women's experiences of the relatively uncommon postnatal
      illness of puerperal psychosis, and to gain understanding into living through and
      past the illness. DESIGN: An interview-based study using grounded theory
      principles to analyse the qualitative data. METHODS: Interviews were conducted
      with 10 women who had been diagnosed and treated for puerperal psychosis (defined
      according to DSM-IV criteria, with onset within six weeks of childbirth) during
      the last 10 years. RESULTS: Three main categories were identified from the
      interviews: puerperal psychosis as a separate form of mental illness, loss, and
      relationships and social rules. Further, two higher order concepts were
      identified, termed 'living with emotions' and 'regaining and changing self'.
      These concepts emerged across, and linked, the categories previously identified.
      CONCLUSIONS: Women felt that the illness took away the ability to experience
      normal emotions, as affective responses were viewed as potentially pathogenic.
      Although puerperal psychosis was described as a life-changing experience, the
      women used feeling like their 'old sense of self' as a marker for recovery. Anger
      and frustration were directed towards health services because of their lack of
      provision of adequate information and support for the women and their families.
      More support may have alleviated the stresses placed on relationships and
      informed families about the nature of the illness. Further work is needed to
      establish the long-term effects of suffering from puerperal psychosis.

PMID- 14670190
TI  - An interview study of people with learning disabilities' experience of, and
      satisfaction with, group analytic therapy.
AB  - A number of clinicians have developed psychodynamic treatments for people with
      learning disabilities, but there have been few studies assessing the impact of
      psychodynamic therapy with this population. In particular, there have been no
      studies in which investigators have asked clients about their experience of
      psychodynamic treatment. The current study is an attempt to rectify this by
      exploring people with learning disabilities' experiences of, and satisfaction
      with, two psychodynamic groups provided by an inner city service. Nine learning
      disabled clients, four from a sexual offenders' group and five from a women's
      group, were interviewed about their experience of psychodynamic group
      psychotherapy. Their responses were analysed using Interpretive Phenomenological
      Analysis. Participants suggested that they valued the therapists and the group,
      and appreciated the opportunity to talk about painful experiences and be included
      and valued in the group. However, participants also indicated that they found the
      group emotionally painful, on occasion found it hard to identify with other group
      members, and were often unaware of any positive change in themselves. These
      interview findings complement ongoing quantitative attempts to establish the
      impact of psychodynamic treatment for this population.

PMID- 14670192
TI  - The Million Women Study and breast cancer.

PMID- 14670193
TI  - Chairman's report.

PMID- 14670194
TI  - Falls and fractures in postmenopausal women: a review.
AB  - Older people are a major risk group for falls. 35-40% of over-65s living at home
      fall at least once a year, and between a third and a half of these fall twice or
      more. The figure rises to 50% for the over-80s. Falls contribute to the
      occurrence of fractures. Of all the fractures linked to osteoporosis and falls,
      hip fractures are the most important in terms of early death, functional
      dependence, and costs of care. Many identifiable risk factors have been shown to
      contribute to hip fracture risk, including low bone density, previous fractures,
      clinical risk factors for falls, and low body weight. Interaction has been found
      between falls and osteoporosis in the occurrence of fractures. Prospective
      studies are needed to evaluate whether a combined bone- and fall-directed therapy
      can further decrease the risk for fractures in patients with low bone density and
      an increased fall risk.

PMID- 14670195
TI  - Testosterone and dementia: too much ado about too little data.
AB  - In vitro and animal investigations have indicated that testosterone is
      neuroprotective and reduces the levels of beta-amyloid and the phosphorylation of
      tau (which are considered to be critical to the pathophysiological process that
      leads to the development of Alzheimer's disease (AD)). Such findings imply that
      testosterone may have an important role in the modulation of cognitive function
      and in reducing the risk of AD. Currently available clinical evidence of the
      association between testosterone and cognitive function/AD comes from a small
      number of cross-sectional studies and five randomised trials of testosterone
      supplementation for healthy older men. The results suggest that testosterone has
      a weak association with visuospatial and memory scores, but the findings are
      inconsistent across different studies, which often included multiple comparisons
      across a wide range of cognitive domains. In addition, the serum levels of
      testosterone in men with AD are comparable to those of controls, as are brain
      levels. In conclusion, currently available evidence does not support the
      existence of a strong association between testosterone and cognitive function/AD.

PMID- 14670196
TI  - Assessment of urinary incontinence.
AB  - Urinary incontinence is a highly prevalent condition in women in their post
      reproductive years. It is becoming an increasingly common presenting complaint as
      population demographics continue to change and further emphasis is placed on
      improving quality of life in this group of women. A wide variety of tools are
      available to assess the extent of the clinical problem and the impact that this
      has on psychosocial function. Many different health specialities are involved in
      caring for this group of patients, including general practitioners,
      gynaecologists, urologists, physiotherapists, and continence nurses. It is
      important to individualise each patient's assessment starting with a medical
      history and examination and leading on to appropriate specialist investigations.

PMID- 14670197
TI  - Assessment of abnormal bleeding in menopausal women: an update.
AB  - Peri and postmenopausal bleeding, with or without the use of hormone replacement
      therapy, is a common clinical problem. The exclusion of endometrial hyperplasia
      and carcinoma is the key issue in the evaluation of patients with abnormal
      uterine bleeding. Transvaginal ultrasound measurement of endometrial thickness
      has become a routine procedure and an initial investigation in patients with
      abnormal uterine bleeding. There is debate as to whether a cut-off of 5 or 4 mm
      endometrial thickness should be employed. If the endometrial thickness is above
      these values, polyps have been diagnosed or the patient is presenting with
      recurrent bleeding, endometrial disease has to be excluded by histological
      assessment. Outpatient aspiration curettage has superseded dilatation and
      curettage, which was previously considered to be the gold standard for obtaining
      endometrial tissue, and provides the same sensitivity in detecting endometrial
      disease. Hysteroscopy allows visualisation of the uterine cavity and the
      opportunity for targeted biopsy and removal of endometrial polyps.

PMID- 14670198
TI  - Contraception in the perimenopause.
AB  - The perimenopause is a stage of life when a woman has low fertility but still
      requires contraception. It is also a peak age for menstrual dysfunction and a
      time when menopausal symptoms may commence. All these factors impact on
      contraceptive choice. Combined oral contraception can be continued until the age
      of 50 years in women who are low risk and do not smoke. Progestogen-only methods
      have advantages for women who have risk factors for cardiovascular disease. An
      intrauterine device may exacerbate menstrual problems at this stage but the
      levonorgestrel releasing intrauterine system is highly effective in controlling
      perimenopausal menstrual dysfunction. Women should receive accurate
      individualised advice on how the risks and benefits of contraceptive methods
      relate to them and on when contraception can be safely discontinued. Hormone
      replacement therapy is not reliably contraceptive and women should be advised to
      continue with a contraceptive method until they have reached natural sterility.

PMID- 14670199
TI  - Managing the menopause - British Menopause Society Council consensus statement on
      hormone replacement therapy.
AB  - The British Menopause Society Council aims to aid health professionals to inform
      and advise women about the menopause. The oestrogen plus progestogen arm of the
      Women's Health Initiative was stopped in July 2002. This guidance regarding
      hormone replacement therapy (HRT) use responds to the results and analysis that
      have been published since then. Because there are few effective alternatives to
      HRT for vasomotor and urogenital symptoms, oestrogen-based treatments still have
      a major role. HRT is also most effective for prevention of osteoporosis.
      Unopposed oestrogens are contraindicated in women with an intact uterus, and
      hence a range of oestrogen and progestogen combinations, with differing routes of
      delivery, now exists under the title of "HRT". Treatment choice should be based
      on up to date information and targeted to individual women's needs. Hormone
      replacement still offers the potential for benefit to outweigh harm, providing
      the appropriate regimen has been instigated in terms of dose, route and
      combination.

PMID- 14670201
TI  - Children's understanding of illness: the generalization of illness according to
      exemplar.
AB  - Using children's naive theory of biology as a framework, this study examined
      children's illness conceptions. Children (aged 4-11), presented with one of four
      exemplars (child, dog, duck or rosebush) suffering an imaginary illness, were
      asked whether various entities from six categories, biological and non
      biological, could also be afflicted. The children's illness generalizations
      differentiated between all of the categories; they not only distinguished between
      living and non-living things, but also recognized biological subkinds.
      Furthermore, the children's generalizations were significantly greater to the
      category of exemplar, indicating that human prototypicality is not the sole basis
      for children's generalizations. It is concluded that children's understanding of
      illness is mediated by a naive biological theory that facilitates their
      systematic predictions of susceptibility to illness.

PMID- 14670202
TI  - Psychological and physical health correlates of coping in minority adolescents.
AB  - In the current study the relations between coping and psychological/physical
      health in a sample of minority adolescents was investigated. Participants (n =
      182) were all low-income, first-generation college-bound students from
      historically underrepresented groups. For Mexican-Americans, positive
      reinterpretation, focusing and venting emotions, instrumental social support,
      active coping, religious, restraint, emotional support, acceptance and planning
      forms of coping were all associated with positive psychological and physical
      health; for African-Americans, coping methods were not significantly associated
      with psychological or physical health; for Asian-Americans, positive
      reinterpretation, active coping, religious coping, restraint, acceptance and
      planning forms of coping were associated with only psychological health. Cultural
      specific (rather than gender-specific) socialization is identified as a potential
      explanation of these results.

PMID- 14670203
TI  - The effects of low and moderate intensity exercise on subjective experiences in a
      naturalistic health and fitness club setting.
AB  - The purpose of this study was to compare the effects of participation in low and
      moderate intensity exercise on subjective exercise experiences in a naturalistic
      health club setting. Thirty physically active members of a community health and
      fitness club participated in low and moderate intensity cycle ergometry for 20
      minutes. Subjective exercise experiences were measured before, during and after
      exercise. Participants reported significant increases in Positive Well-being and
      Fatigue scores across time in the moderate but no change in the low exercise
      intensity condition. The results suggest that exercising for 20 minutes at
      moderate intensity in a health club environment provides some measure of
      psychological benefit for a general population, although exercise at the higher
      intensity could have negative implications by increasing feelings of fatigue
      during and after exercise.

PMID- 14670204
TI  - Illness perceptions in people with acute bacterial gastro-enteritis.
AB  - Functional gastro-intestinal disorders (FGID) like irritable bowel syndrome (IBS)
      are common and can develop after gastro-enteritis. Illness representations may be
      important influences on the development of post-infectious FGIDs. Here, we
      studied both the relationship between prior chronic symptoms (FGIDs) and illness
      perception during an acute illness (bacterial gastro-enteritis) as well as the
      relationship between illness perception during an acute illness (bacterial gastro
      enteritis) and the subsequent development of chronic abdominal symptoms. Two
      hundred and seventeen people with recent gastro-enteritis completed a
      questionnaire asking about gut symptoms consistent with a diagnosis of IBS,
      functional dyspepsia or functional diarrhoea and the Illness Perception
      Questionnaire. Those without a prior FGID were followed up and completed a
      similar gut questionnaire at six months. People with a prior FGID had
      significantly more symptoms and scored significantly higher on the timeline and
      consequence scores than those without. People who developed a FGID had a non
      significantly higher number of symptoms and higher consequence and timeline
      scores than those who did not. Neither comparative group differed in the
      control/cure scores or causation scores. The implications of the findings are
      discussed.

PMID- 14670205
TI  - Psychosocial factors related to the correspondence of recipient and provider
      perceptions of social support among patients diagnosed with or at risk for
      malignant melanoma.
AB  - This study examined considered perceptions of social support and factors
      contributing to increased support among 18 patients diagnosed with or at risk for
      malignant melanoma and their partners. Partner support, perceived stress,
      emotional approach coping and partner empathy were evaluated. Results showed lack
      of correspondence between patient and partner reports of support. Greater
      correspondence between reports was associated with increased patient emotional
      approach coping. Partners reported increased empathy following the patients'
      diagnoses and more perceived stress than patients. Patients indicated greater use
      of emotional approach coping than their partners. Male partners reported engaging
      in less emotional expression than female partners. Interventions might
      incorporate partner participation to resolve misperceptions of support and to
      foster factors that promote increased support.

PMID- 14670206
TI  - Cancer narratives and the cancer support group.
AB  - We conceptualize the experience of cancer as requiring 'biographical work' and
      examine the nature of this work in the context of peer support groups. Interviews
      with participants and leaders of support groups were used to theorize the
      importance of support to cancer patients with varying stages and length of
      disease. Patient interviews led us to describe the process of joining, belonging,
      and identifying with, support groups as an important process within patients'
      ongoing biographical work and encompassing a search for a 'separate social
      space'. We discuss the implications for understanding the stigmatizing nature of
      cancer and the 'civic life' these groups support.

PMID- 14670207
TI  - Perceived barriers to social support from family and friends among older adults
      with HIV/AIDS.
AB  - Research has found that HIV-infected adults age 50 and older are more socially
      isolated than younger HIV-infected individuals. This study examines the perceived
      barriers to obtaining emotional and practical social support from friends and
      family among 63 older adults (age 50+) living with HIV/AIDS. Many reported they
      did not receive enough emotional support (42%) or practical assistance (27%).
      Barriers to obtaining support included: (1) nondisclosure of HIV status; (2)
      others' fear of HIV/AIDS; (3) desire to be self-reliant and independent; (4) not
      wanting to be a burden; (5) unavailability of family; (6) death of friends to
      AIDS; and (7) ageism. These barriers may explain the greater social isolation of
      HIV-infected older adults and inform interventions targeted at reducing these
      barriers.

PMID- 14670208
TI  - Factor structure, validity and reliability of the Cambridge Worry Scale in a
      pregnant population.
AB  - This article presents the Cambridge Worry Scale (CWS), a content-based measure
      for assessing worries, and discusses its psychometric properties based on a
      longitudinal study of 1,207 pregnant women. Principal components analysis
      revealed a four-factor structure of women's concerns during pregnancy: socio
      medical, own health, socio-economic and relational. The measure demonstrated good
      reliability and validity. Total CWS scores were strongly associated with state
      and trait anxiety (convergent validity) but also had significant and unique
      predictive value for mood outcomes (discriminant validity). The CWS discriminated
      better between women with different reproductive histories than measures of state
      and trait anxiety. We conclude that the CWS is a reliable and valid tool for
      assessing the extent and content of worries in specific situations.

PMID- 14670209
TI  - Youth culture and smoking: Integrating social group processes and individual
      cognitive processes in a model of health-related behaviours.
AB  - This article assesses four theoretical models proposed to predict future smoking.
      Young adults were surveyed at three six-month intervals, the first occurring
      three months after leaving school. Models 1 and 2 were versions of theory of
      triadic influence (TTI), which links a person's behavioural experience and
      cognitions to their future behaviour. Model 1 did not fit the data; the fit of
      model 2 was just adequate. Model 3 combined TTI and self-categorization theory
      (ST), by allowing norms of the individual's peer group to influence cognitions
      and future behaviour. It fitted the data well. Model 4, which extended model,
      provided the best fit. Strength of identification to the peer group was found to
      enhance the effect of the peer group norm.

PMID- 14670210
TI  - Development of the York Angina Beliefs Questionnaire.
AB  - It is known that people who have suffered a heart attack can hold misconceived or
      maladaptive beliefs and that these can have a deleterious effect on quality of
      life and functioning. It has also been noted that clinicians do not routinely
      elicit these maladaptive beliefs. It is probable that angina sufferers also hold
      such beliefs. As angina is a great burden in the western world, with over two
      million people with angina in the UK alone, there may be large numbers of people
      who suffer from these frightening and unhelpful misconceptions. We believe that
      there is a need for a simple questionnaire that could assist the delivery of
      tailored education directed at dispelling common misconceptions. This article
      details the development and psychometric properties of just such a brief
      questionnaire, designed for use both in research and in clinical practice.

PMID- 14670211
TI  - Narratives of obesity as presented in the context of a television talk show.
AB  - Media representations of health and illness have come under scrutiny for their
      ability to mislead and misinform the public about health issues. However, the
      media also provide a public forum in which talk about health and illness may be
      circulated in a more positive fashion. This article consists of a narrative
      analysis of an episode of the BBC talk show Kilroy, in which the topic of obesity
      is discussed by the show's host and a group of lay guests. Two narratives in
      particular are examined for their similarities and differences. Both are
      structured around the idea of a 'turning point' that results in successful
      recovery from obesity, although what constitutes recovery differs in both cases,
      and is linked to the overall structure of the narrative. It is argued that
      personal narratives are important conceptual tools for health psychologists to
      work with, although we cannot lose sight of the mediated context in which these
      data are produced.

PMID- 14670212
TI  - 'Hirsutism': a psychological analysis.
AB  - Hirsutism, i.e. 'excess' body hair in the 'male' distribution, is a medical term
      applied only to women. Although associated with social and psychological
      difficulties including anxiety, social avoidance and a confusion of gender
      identity and although it raises important gender issues, there has been little
      systematic study. No prior research has focussed on the relationship between
      women's perceived degree of hirsutism and psychological distress. A survey of 53
      women with polycystic ovary syndrome (PCOS), which often produces 'excess' hair
      growth, was carried out to assess any psychological consequences of perceived
      hirsutism. Results indicated raised levels of psychological distress overall, but
      no significant relationships between perceived hirsutism and distress. Four semi
      structured interviews were then conducted to facilitate more in-depth exploration
      of hirsute women's experience. Analysis suggested idealized cultural norms for
      hair growth prevail and excess hair growth contributes to gender inconsistencies
      and feelings of deviance and stigma. Effective concealment of hair growth and
      'passing' for normal appear to facilitate relatively high levels of functioning
      and allows idealized cultural norms to be maintained.

PMID- 14670213
TI  - From 'I Wish' to 'I Will': social-cognitive predictors of behavioral intentions.
AB  - We tested the ability of several social-cognitive models to predict intentions to
      engage in two different health behaviors (resisting dieting and performing breast
      self-exam). All constructs from the health belief model (with and without self
      efficacy), the theory of planned behavior (with and without perceived behavioral
      control) and the motivational process of the health action process approach were
      measured simultaneously in two subject samples. We hypothesized that models that
      include self-efficacy (or the related construct of perceived behavioral control)
      would be more effective than the models that do not include it. Our results
      supported this prediction. The health action process approach was the best
      predictor of intentions to engage in both behaviors. Implications for selecting
      appropriate models on which to base interventions are discussed.

PMID- 14670214
TI  - Control constructs: Do they mediate the relation between educational attainment
      and health behaviour?
AB  - Health promoting behaviours seem to be more prevalent among people with higher
      socio-economic status (SES). The main purpose of this article was to study (a)
      the relationship between education (as a dimension of SES) and intention and
      health behaviour (fruit/vegetable consumption), (b) the relationship between
      education and control conceptualizations (health locus of control (HLC), response
      efficacy and self-efficacy) and (c) to what extent the relationship between
      education and intention/health behaviour (fruit/vegetable consumption) was
      mediated through different control beliefs. The results showed that women with
      higher education had higher intentions to consume fruit/vegetables and consumed
      fruit/vegetables more frequently. Higher education was associated with higher
      self-efficacy and response-efficacy beliefs and less belief in HLC-chance. These
      control beliefs partly mediated the education-intention/behaviour relationship.

PMID- 14670215
TI  - Perceived risk of bovine spongiform encephalopathy and dietary behavior.
AB  - The German BSE crisis in early 2001 can be considered as a natural experiment
      with strong behavioral consequences. The present study investigated psychological
      and other factors associated with reduced meat consumption compared to the first
      months of the previous year. As expected, all types of meat, with the exception
      of poultry and game, were eaten less often. The effect was strongest in beef,
      where almost half of the sample reported reduced meat consumption. As predicted
      by the health belief model, perceived threat was associated with subjective
      vulnerability. It was not, however, strongly associated with perceived
      seriousness of BSE, probably due to the ubiquitous public discussion of the
      topic. Reduced beef consumption has three to four times more frequent in the
      event of subjective threat.

PMID- 14670216
TI  - Spirituality, breast cancer beliefs and mammography utilization among urban
      African American women.
AB  - Spirituality has been shown to be associated with health, and is an important
      component in the lives of many African Americans. Recent research proposes that
      spirituality is a multidimensional construct. The present study proposes a two
      dimensional model in which spirituality encompasses a belief and behavioral
      dimension. This hypothesis was examined, as were relationships between these
      dimensions and spiritual health locus of control, breast cancer beliefs and
      mammography utilization among African American women. The belief dimension played
      a more important role in adaptive breast cancer beliefs and mammography
      utilization that did the behavioral dimension. These findings suggest the
      importance of spiritual belief systems for health, and implications for spiritual
      cancer communication interventions are discussed.

PMID- 14670217
TI  - The impact of screening on future health-promoting behaviours and health beliefs:
      a systematic review.
AB  - OBJECTIVES: To carry out a systematic review to examine the effects of
      cholesterol, breast and cervical cancer screening on actual or intended health
      promoting behaviours and health-related beliefs. DATA SOURCES: Eleven electronic
      databases (between 1980 and 2000). REVIEW METHODS: All English language studies
      that investigated the impact of cholesterol, breast and cervical screening
      programmes on health-promoting behaviours and beliefs were assessed for
      inclusion. The data extraction form and quality assessment criteria were
      developed using the NHS Centre for Reviews and Dissemination guidelines. Data
      were extracted and a non-quantitative synthesis was conducted. Reviewers
      categorised the outcomes into those that could be considered beneficial or
      detrimental to health. This categorisation was based on a value judgement that
      considered both statistical and clinical significance. RESULTS: The cholesterol
      studies used prospective designs more frequently, possibly as many focused on
      observing changes in lifestyle following screening. Participants who went for
      breast or cervical screening were not offered advice on lifestyle changes and
      most of the research into cancer screening programmes investigated issues related
      to uptake of screening services, explanations of why people are or are not
      screened and interventions to improve uptake. All three screening programmes are
      associated with high levels of favourable health behaviours and beliefs that have
      been measured, although there is evidence that recommended follow-up after
      screening is often not adhered to. There was no literature on the cost
      effectiveness regarding the wider implications of screening (only on reduction of
      disease-specific mortality/morbidity), possibly due to the outcomes being very
      broad and not easily categorised and classified. CONCLUSIONS: The studies
      reviewed suggest that cholesterol screening had a positive effect on health
      behaviours, although participation was voluntary and those screened were possibly
      more motivated to make changes. These results are therefore not generalisable to
      the entire population and other factors need to be taken into account. Reduction
      in blood cholesterol levels was reported in all but two of the studies that
      assessed this outcome, suggesting that successful lifestyle changes were made.
      However, as most of the studies only reported follow-up of those screened, some
      of the reduction can be attributable to regression to the mean. Whether breast
      and cervical screening affect future health behaviours and beliefs has not been
      directly measured in many studies and few studies have collected baseline
      measures. However, evidence suggests that women who attend breast and cervical
      screening once are likely to reattend and attendance is associated with several
      positive health behaviours, although it cannot be confirmed whether the
      associations observed were a result of screening or because these women have a
      certain set of health behaviours and beliefs irrespective of their experience of
      screening. Areas of further research include: measuring a much wider range of
      behaviours and beliefs before and after screening is accepted or declined,
      examining the subgroup of participants who receive 'desirable' results and the
      impact of this on health beliefs and health-promoting behaviour, and qualitative
      research into the experiences of screening and how this interacts with knowledge
      and beliefs about other aspects of health.

PMID- 14670218
TI  - The inclusion of reports of randomised trials published in languages other than
      English in systematic reviews.
AB  - OBJECTIVE: To assemble a large dataset of language restricted and language
      inclusive systematic reviews, including both conventional medicinal (CM) and
      complementary and alternative medicine (CAM) interventions. To then assess the
      quality of these reports by considering and comparing different types of
      systematic reviews and their associated RCTs; CM and CAM interventions; the
      effect of language restrictions compared with language inclusions, and whether
      these results are influenced by other issues, including statistical heterogeneity
      and publication bias, in the systematic review process. DATA SOURCES: MEDLINE,
      EMBASE, the Cochrane Database of Systematic Reviews and the Centralised
      Information Service for Complementary Medicine. REVIEW METHODS: Three types of
      systematic reviews were included: language restricted; language inclusive/English
      language (EL) reviews that searched RCTs in languages other than English (LOE)
      but did not find any and, hence, could not include any, in the quantitative data
      synthesis; and systematic reviews that searched for RCTs in LOE and included them
      in the quantitative data synthesis. Fisher's exact test was applied to compare
      the three different types of systematic reviews with respect to their reporting
      characteristics and the systematic review quality assessment tool. The odds ratio
      of LOE trials versus EL trials was computed for each review and this information
      was pooled across the reviews to examine the influence that language of
      publication and type of intervention (CM, CAM) have on the estimates of
      intervention effect. Several sensitivity analyses were performed. RESULTS: The
      LOE RCTs were predominantly in French and German. Language inclusive/LOE
      systematic reviews were of the highest quality compared with the other types of
      reviews. The CAM reviews were of higher quality compared with the CM reviews.
      There were only minor differences in the quality of reports of EL RCTs compared
      with the eight other languages considered. However, there are inconsistent
      differences in the quality of LOE reports depending on the intervention type. The
      results, and those reported previously, suggest that excluding reports of RCTs in
      LOE from the analytical part of a systematic review is reasonable. Because the
      present research and previous efforts have not included every type of CM RCT and
      the resulting possibility of the uncertainty as to when bias will be present by
      excluding LOE, it is always prudent to perform a comprehensive search for all
      evidence. This result only applies to reviews investigating the benefits of CM
      interventions. This does not imply that systematic reviewers should neglect
      reports in LOE. We recommend that systematic reviewers search for reports
      regardless of the language. There may be merit in including them in some aspects
      of the review process although this decision is likely to depend on several
      factors, including fiscal and other resources being available. Language
      restrictions significantly shift the estimates of an intervention's effectiveness
      when the intervention is CAM. Here, excluding trials reported in LOE, compared
      with their inclusion, resulted in a reduced intervention effect. The present
      results do not appear to be influenced by statistical heterogeneity and
      publication bias. CONCLUSIONS: With the exception of CAM systematic reviews, the
      quality of recently published systematic reviews is less than optimal. Language
      inclusive/LOE systematic reviews appear to be a marker for a better quality
      systematic review. Language restrictions do not appear to bias the estimates of a
      conventional intervention's effectiveness. However, there is substantial bias in
      the results of a CAM systematic review if LOE reports are excluded from it.

PMID- 14670219
TI  - A kind of Mozart of medicine: Joseph Plenck (1735-1807).
AB  - This is a tribute to one of the fathers of modern European dermatology and
      venereology, Dr Joseph Plenck, the Viennese protodermatologist of two hundred
      years ago, 1735-1807, who was professor and secretary of the Imperial Medical
      Josephine Academy, where today is the Institute for the history of medicine.
      Plenck introduced the systematization of dermatovenereological diseases based on
      their paradigmatic differences, which is deemed as "the only (system) with
      pretensions to accuracy". A man of diversified interests and a fruitful author,
      he wrote many treatises covering various fields from dermatology, venereology,
      and dentistry to surgery, obstetrics, anatomy, pediatrics, pharmacology, and
      botany. This remarkable physician definitely left a deep trace in the history of
      dermatology and venereology, and marked the transition from text-based to
      visually dependent culture in the field of dermatovenereology.

PMID- 14670220
TI  - Familial cutaneous and uterine leiomyomas: case report.
AB  - Cutaneous leiomyomas are rare, benign tumors arising from the arrectores pilorum
      muscles of the skin, the tunica dartos of the scrotum, muscles of the areola of
      the nipple, and vulvar or vascular smooth muscles. Multiple cutaneous leiomyomas
      originate from the arrectores pilorum muscles of the skin (piloleiomyomata
      cutis). Occasionally, they seem hereditary and may be associated with uterine
      myomas. We present a family in which the mother and 4 of her 6 daughters had
      uterine myomas. All sisters had to undergo hysterectomy before the age of 40, and
      three of them had multiple cutaneous leiomyomas simultaneously. Our observations
      support the suggestion that this kind of leiomyomas is a disorder with autosomal
      dominant inheritance with incomplete gene penetration. Moreover, the data
      indicate the necessity of periodical examinations to rule out the presence of
      uterine myomas not only in cutaneous leiomyoma patients, but also in other women
      in a given family.

PMID- 14670221
TI  - Syphilitic aneurysm: case report.
AB  - Tertiary syphilis is a rare, slowly progressive inflammatory disease that becomes
      clinically visible years after initial infection. Although it can affect any
      organ in the body, it shows a predilection for the cardiovascular and nervous
      systems. Today, however, cardiovascular syphilis is a medical curiosity because
      the disease can successfully be treated with antibiotics in its early phase. We
      present a case of a 43-year-old male patient with a syphilitic aneurysm of the
      descendent aorta and our choice of treatment.

PMID- 14670222
TI  - Nevus comedonicus--case report and review of therapeutical approach.
AB  - Nevus comedonicus is uncommon abnormality of pilosebaceous unit, clinically
      characterized as confluent clusters of dilated follicular orifices plugged with
      pigmented keratinous material that resembles open comedones. It is suggested that
      nevus comedonicus is an uncommon variant of adnexal hamartoma, which clinically
      appears as linear group of open comedones. Since Kofmann's description of nevus
      comedonicus in 1895, there have been reports of this rare cutaneous disorder
      associated with developmental anomalies. We present a case of a 19-year-old woman
      with numerous 1-3 mm size darkly pigmented, keratic plugs clustered in linear
      unilateral patches on left abdominal part. Our treatment consisted of the
      avoidance of the formulations containing nickel sulfate and carba mixture, daily
      local application of tretinoin 0.1% gel and corticosteroid ointment (momethasone
      furoate). After 4 weeks of local therapy cosmetic result was evident. The slight
      resolution of keratin plugs could also be seen. Two months after the treatment,
      there were no visible skin exacerbations.

PMID- 14670223
TI  - Protein p53--structure, function, and possible therapeutic implications.
AB  - Cell cycle is driven by a number of positive and negative regulatory
      phosphorylation and dephosphorylation events that ultimately influence the
      activity of transcription factors. Normal skin architecture depends on the
      regulation mechanisms of cell proliferation and differentiation and on apoptosis.
      Complex interaction of different factors in the regulation of these mechanisms,
      aimed at maintaining constant desquamation, is often changed in skin diseases.
      The main difference between normal cells and tumor cells results from discrete
      changes in specific genes important for cell proliferation control mechanisms and
      tissue homeostasis. These genes are mainly proto-oncogenes or tumor-suppressor
      genes, and their mutation could play a role in cell hyperproliferation and
      carcinogenesis. Tumor-suppressor genes normally function as a physiological
      barrier against clonal expansion or mutation accumulation in the genome. They
      also control and arrest growth of the cells that hyperproliferate due to oncogene
      activity. Alteration or DNA damage in tumor-suppressor genes and oncogenes are
      considered key events in human carcinogenesis. Tumor-suppressor protein p53 is an
      important transcription factor, which plays a central role in the cell cycle
      regulation mechanisms and cell proliferation control, and its inactivation is
      considered a key event in human carcinogenesis. The role of p53 protein in the
      cell cycle, high proportion of tumors with mutated p53 gene, and accumulation of
      significant amount of knowledge on molecular biology of this protein make this
      molecule especially attractive for development of new therapeutic approaches.
      Main strategies for development of new antineoplastic therapies are based on
      "wild-type" p53 protein acting as a tumor suppressor, selective apoptosis
      inductor, and a protein able to arrest cell cycle.

PMID- 14670224
TI  - Stomatodynia or burning mouth syndrome.
AB  - We reviewed the literature on stomatodynia particularly to identify the factors
      associated with this annoying manifestation in order to better understand it and
      treat it. No consensus was found in the literature regarding etiological factors,
      associated morbidity, treatment, and definition of the burning mouth syndrome.
      This review aims at defining the disease, its characteristics, criteria for the
      diagnosis, and treatment.

PMID- 14670225
TI  - Etiopathogenesis, classification, and current trends in treatment of rosacea.
AB  - Rosacea is a common chronic dermatosis characterized by varying degrees of
      flushing, erythema, telangiectasia, edema, papules, pustules, ocular lesions, and
      phymas. Etiology and pathogenesis of rosacea are still unknown. Many possible
      causes have been described as inducing the disease or contributing to its
      manifestation, such as genetic predisposition, abnormal vascular reactivity,
      changes in vascular mediating mechanisms, Helicobacter pylori infection, Demodex
      folliculorum infestation, seborrhea, sunlight, hypertension, and psychogenic
      factors. However, none of these factors has been proved. Rosacea shows a wide
      spectrum of clinical presentations, which vary over time and with age. Successful
      management of rosacea requires careful patient evaluation and individualized
      therapy with appropriate variations and modifications, as the severity of the
      disorder fluctuates. In mild cases of rosacea, patients are instructed to avoid
      sun, to apply sun-protective creams, and to avoid facial irritants and other
      triggers that provoke symptoms. At later stage, drug therapy is often necessary.
      The disease commonly requires long-term treatment with topical or oral
      medicaments. Surgical correction may be required for rhinophyma and
      telangiectasia. We reviewed the current literature on the aspects of the
      pathogenesis, diagnostic criteria, and treatment options for rosacea.

PMID- 14670226
TI  - Still elusive relationship between atopic dermatitis and allergic contact
      dermatitis.
AB  - The relationship between atopic dermatitis (AD) and allergic contact dermatitis
      (ACD) has long been and continues to be an unsolved and frequently discussed
      issue. Whereas AD patients have traditionally been considered to have a decreased
      frequency of ACD, recent studies revealed that these individuals are more or
      equally likely to develop ACD. The aim of the present review was to determine
      whether the results of recent experimental studies and theoretical considerations
      might lead to a parallel shift in our concept on the causal relationship between
      AD and ACD. It has been shown that Th2 and Th1-type immune responses are not
      mutually exclusive, and that at least in AD a mixture of both Th2 and Th1 occurs
      and the interactions between them account for the clinical characteristics of the
      disease. This new concept on the immunopathomechanism of AD challenges our
      previous belief that the cytokine pattern of the affected skin is unsuitable for
      the development of delayed-type hypersensitivity. Since we do not know the exact
      quantitative balance between Th1 and Th2 reactions along a time axis, we cannot
      predict whether the cytokine pattern of AD patients favors or inhibits the
      development of ACD. What we do know with a greater degree of certainty, is that
      when the eczematous excoriated skin of AD patients, with its defective epidermal
      barrier (enhancing the penetration of many antigenic substances) is chronically
      exposed to skin care products and various sensitizing topical medications, it is
      more likely to develop a superimposed ACD.

PMID- 14670227
TI  - Preparation and characterization of diacetylene polymerized liposomes for
      detection of autoantibodies.
AB  - Affinity diacetylene liposomes were prepared with 10,12-tricosadiynoic acid and
      cardiolipin as the affinity ligand for anticardiolipin antibodies at a molar
      ratio of 80:20. Polymerization was carried out under UV irradiation, and the
      color transitions were monitored by visible absorption spectroscopy. Peaks at 635
      nm (blue form), 540 nm (purple form), and 480 nm (red form) were observed as a
      function of time. These polymerized liposomes were used in a noncompetitive
      immunoassay for detection of anticardiolipin antibodies. Color changes were
      observed when reference serum containing specific immunoglobulin G, IgG, was
      added to polymerized liposome dispersions. The colorimetric signal due to IgG
      adsorption on the liposome surface was quantified as a colorimetric response
      defined as the change in percentage of blue color related to the initial
      percentage of blue color in the solutions. The colorimetric response was 10 times
      higher for specific IgG compared with nonspecific ones. These results suggest the
      unique potentialities of affinity diacetylene polymerized liposomes in the
      development of biosensors for diagnosis of autoimmune diseases.

PMID- 14670228
TI  - Interaction of the water-soluble protein aprotinin with liposomes: gel
      filtration, turbidity studies, and 31P NMR studies.
AB  - The interactions of a water-soluble nonmembrane protein aprotinin with
      multilamellar vesicles (MLV) and small unilamellar vesicles (SUV) from soybean
      phospholipids were studied using Sephadex G-75 gel chromatography combined with
      different methods of the analysis of the eluate fractions (fluorescence, light
      scattering, turbidity; 31P NMR spectroscopy). The composition of the liposomes
      mainly containing soybean phosphatidylcholine (PC) was varied by the addition of
      phosphatidylethanolamine (PE), phosphatidylinositol (PI) and lyso
      phosphatidylcholine (lyso-PC). To evaluate the lipid-protein interactions, the
      amount of aprotinin in the MLV-aprotinin complexes was determined. Lipid-protein
      interactions were found to strongly depend on the liposome composition, medium pH
      and ionic strength. These dependencies point to the electrostatic nature of the
      aprotinin-lipid interactions. 31P NMR spectroscopy of the MLV-aprotinin complexes
      indicated that aprotinin influences the phospholipid structure in MLV at pH 3.0.
      In the case of PC:PE:PI and PC:PE:PI:lyso-PC vesicles, aprotinin induced liposome
      aggregation and a lamellar-to-isotropic phase transition of the phospholipids.

PMID- 14670229
TI  - Targeting of lipid-protamine-DNA (LPD) lipopolyplexes using RGD motifs.
AB  - The incorporation of pegylated lipid into Lipid-Protamine-DNA (LPD-PEG)
      lipopolyplexes causes a decrease of their in vitro transfection activity. This
      can be partially attributed to a reduction in particle binding to cells. To
      restore particle binding and specifically target LPD formulations to tumor cells,
      the lipid-peptide conjugate DSPE-PEG5K-succinyl-ACDCRGDCFCG-COOH (DSPE-PEG5K-RGD
      4C) was generated and incorporated into LPD formulations (LPD-PEG-RGD). LPD-PEG
      RGD was characterized with respect to its biophysical and biological properties.
      The Incorporation of DSPE-PEG5K-RGD-4C ligands into LPD formulations results in a
      5 and a 15 fold increase in the LPD-PEG-RGD binding and uptake, respectively,
      over an LPD-PEG formulation. Enhancement of binding and uptake resulted in a 100
      fold enhancement of transfection activity. Moreover, this transfection
      enhancement was specific to cells expressing appropriate integrin receptors (MDA
      MB-231). Huh7 cells, known for their low level of alphavbeta3 and alphavbeta5
      integrin expression, failed to show RGD mediated transfection enhancement. This
      transfection enhancement can be abolished in a competitive manner using free RGD
      peptide, but not an RGE control peptide. Results demonstrated RGD mediated
      enhanced LPD-PEG cell binding and transfection in cells expressing the integrin
      receptor. These formulations provide the basis for effective, targeted, systemic
      gene delivery.

PMID- 14670230
TI  - The interaction of DMSO with model membranes. I. Comparison of DMSO and d6-DMSO:
      a DSC and IR investigation.

PMID- 14670231
TI  - The interaction of DMSO with model membranes. II. Direct evidence of DMSO binding
      to membranes: an NMR study.

PMID- 14670232
TI  - Stability of desmopressin loaded in liposomes.
AB  - Desmopressin-containing liposome formulations have been developed for intranasal
      administration previously. Positively charged liposomes were found to be an
      efficient delivery system for desmopressin. In this study, stability of the
      loaded desmopressin in positively charged liposomes was further investigated.
      Comparison of the stability of desmopressin in solution and liposomes was made.
      Degradation of desmopressin was shown to follow a pseudo-first-order reaction.
      Degradation of desmopressin in both solution and liposomes demonstrated the same
      kinetic behavior and exhibited no significant difference in half-lives. Similar v
      shape pH-rate profile was found for desmopressin degradation in solution and
      liposomes. At pH 4.0, the inflection point of the v-shape pH-rate curve, the
      reaction rate of desmopressin was lowest and the stability was greatest. The
      stability of lipid ingredients of dioleoylphosphatidylcholine (DOPC), cholesterol
      (C), and stearylamine (S) in the liposome dispersion at pH 4.0 was studied.
      Results demonstrated that DOPC, C, and S were relatively stable in the liposome
      structure when formulated with desmopressin. The degradation of desmopressin in
      solution and liposomes in the presence of alpha-chymotrypsin was investigated. A
      longer half-life for desmopressin in liposomes than in solution was observed. It
      was suggested that desmopressin was protected by the liposomes against alpha
      chymotrypsin digestion.

PMID- 14670233
TI  - Entrapment of peptidoglycans and adamantyltripeptides into liposomes: an HPLC
      assay for determination of encapsulation efficiency.
AB  - The encapsulation of different immunomodulating peptides, the peptidoglycan
      monomer, its semisynthetic derivatives (Adamant-1-yl)-acetyl-peptidoglycan
      monomer and Boc-Tyr-peptidoglycan monomer, respectively, and of two
      diastereoisomers of adamantyltripeptides into the large negatively charged
      multilamellar liposomes was investigated. The reproducible quantitative method
      using HPLC was established for the determination of the entrapped compounds. It
      was shown that the tested compounds could be efficiently incorporated into
      liposomes using either the film or modified film method. The results confirmed
      that the peptidoglycans with lipophilic substituents and particularly the
      adamantyltripeptides were incorporated into liposomes with higher efficiency than
      the peptidoglycan monomer using either of the described methods. Liposome
      preparations were stable at 4 degrees C up to seven days as shown by minimal
      leaking of the entrapped material.

PMID- 14670234
TI  - [Role of capsule endoscopy in patients with obscure digestive bleeding].
AB  - INTRODUCTION: The identification and localization of lesions located in the small
      intestine that may provoke gastrointestinal bleeding is difficult. OBJECTIVE: To
      analyze the role of capsule endoscopy in patients with obscure digestive bleeding
      and to compare the results obtained with those of enteroscopy. PATIENTS AND
      METHODS: Twenty-one patients with obscure digestive bleeding (acute hemorrhage in
      11 patients and chronic anemia in 10) and normal total fibergastroscopy and
      fibrocolonoscopy were analyzed. All patients were instructed to receive the
      capsule and enteroscopy was performed after 1 week. The results obtained using
      both procedures were independently compared and without knowledge of the results
      of the other procedure. RESULTS: Visualization of findings potentially related to
      gastrointestinal bleeding was significantly greater (p < 0.05) using the capsule
      (14 of 21 patients [66%]) than with enteroscopy (4 of 21 patients [19%]). The
      most frequent lesions were angiodysplasias and jejunal ulcers. In 4 patients, the
      results obtained led to a change in therapeutic approach. One patient with
      jejunal stenosis and two with ileal lesions underwent surgery, which confirmed
      the diagnosis of Crohn's disease in the first patient and carcinoid tumor in the
      remaining two. Another patient with evidence of angiodysplasia and bleeding was
      effectively treated with Argon-beam during enteroscopy. The capsule was well
      tolerated in all patients. In the patient with jejunal stenosis, capsule
      extraction was required during surgery. CONCLUSIONS: Capsule endoscopy allows
      adequate visualization of the entire small intestine and its diagnostic efficacy
      is greater than that of enteroscopy in patients with obscure digestive bleeding.
      Moreover, in our series, this procedure allowed modification of therapy in one
      out of every five patients.

PMID- 14670236
TI  - [Etiology of upper gastrointestinal bleeding of peptic origin: role of
      Helicobacter pylori and NSAIDs].
AB  - INTRODUCTION: Upper gastrointestinal bleeding continues to be a severe and
      frequent complication in ulcerative disease. Etiologic diagnosis in these
      patients is highly important in order to initiate appropriate treatment and
      prevent bleeding recurrence. OBJECTIVE: 1. To investigate the prevalence of
      Helicobacter pylori infection and use of NSAIDs in patients with upper
      gastrointestinal hemorrhage of peptic origin. 2. To analyze the strategy used for
      the diagnosis of H. pylori in our previous work. PATIENTS AND MEHTODS: Seventy
      three patients with endoscopically-diagnosed upper gastrointestinal bleeding of
      peptic origin were included in the study. The use of NSAIDs was investigated. H.
      pylori infection was diagnosed if one of the following tests was positive: urease
      test, histology, breath test. RESULTS: H. pylori infection was found in 92% of
      duodenal ulcers and in 88% of gastric ulcers. Fifty-six percent of the patients
      had taken NSAIDs. Excluding these patients resulted in an H. pylori infection
      rate of 96.7%. The diagnosis was based on urease test in 46%. In the remaining
      patients, breath test and histology were required. CONCLUSIONS: The main etiology
      in patients with upper gastrointestinal bleeding of peptic origin is H. pylori
      infection followed by the use of NSAIDs, and these two factors frequently
      coexist. The strategy of performing a urease test and, when this is negative,
      performing histological study and a breath test, is valid and allows a diagnosis
      of H. pylori infection to be made even if patients are receiving treatment that
      could make diagnosis difficult.

PMID- 14670235
TI  - [Tumoral markers and acute-phase reactants in the diagnosis of pancreatic
      cancer].
AB  - OBJECTIVE: To analyze the diagnostic accuracy of the following parameters in the
      diagnosis of pancreatic cancer: carcinoembryonic antigen (CEA), tissue
      plasminogen activator (TPA), carbohydrate antigen 19-9 (CA 19-9), carbohydrate
      antigen 50 (CA 50), alpha-1-antitrypsin (AAT), alpha-2 macroglobulin (AMG), and
      ceruloplasmin (CP). PATIENTS AND MENTOD: We prospectively studied 58 patients
      with pancreatic cancer, 40 with alcoholic pancreatitis and 40 healthy controls,
      in whom the above-mentioned parameters were analyzed. Receiver operating
      characteristic curves (ROC curves) were analyzed. RESULTS: The specificity of
      TPA, CA 19-9 and CA 50 in the differential diagnosis between pancreatic cancer
      and chronic pancreatitis was 87.5%, 90% and 95% respectively, with a sensitivity
      of nearly 90%. Although levels of AAT, AMG and CP were higher in patients with
      cancer than in those with pancreatitis, their specificity was lower,
      approximately 65%. CEA and TPA showed a positive association with the presence of
      metastases. CONCLUSION: TPA, CA 19-9 and CA 50 were useful in the differential
      diagnosis between pancreatic cancer and chronic pancreatitis.

PMID- 14670237
TI  - [Massive hemorrhage due to nodular hyperplasia of Brunner's glands in
      antiphospholipid syndrome].
AB  - Gastrointestinal hemorrhage is an exceptional complication of antiphospholipid
      syndrome and most reported cases are secondary to ischemic lesions. Brunner's
      gland hyperplasia is an infrequent and usually asymptomatic condition that has
      been associated with chronic renal failure. We report a patient with primary
      antiphospholipid syndrome who, after mechanic heart valve replacement and while
      in a state of drug-induced anticoagulation, experienced a life-threatening upper
      gastrointestinal hemorrhage due to nodular hyperplasia of Brunner's glands. This
      entity may be considered in the differential diagnosis of upper gastrointestinal
      bleeding in patients with antiphospholipid syndrome, most of whom are treated
      with oral anticoagulatory drugs, and particularly in patients with chronic renal
      failure.

PMID- 14670238
TI  - [Bile duct obstruction due to non-Hodkin's lymphoma in patients with HIV
      infection].
AB  - Acquired immune deficiency syndrome increases the risk of developing non
      Hodgkin's B-cell lymphoma (NHL) (relative risk over 100). NHL tend to be high
      grade and to affect the central nervous system and digestive tract. Biliary tract
      compression is usually due to external compression from enlarged lymph nodes, but
      is not usually the first manifestation.We describe 2 cases of bile duct
      obstruction secondary to NHL in patients diagnosed with HIV infection.
      Histological diagnosis of the lymphoma can be difficult but is necessary so that
      these patients do not undergo highly aggressive surgical treatment instead of
      chemotherapy, which currently produces the best results. Therefore, we emphasize
      the importance of including lymphomas in the differential diagnosis of bile duct
      obstruction in patients with HIV infection.

PMID- 14670239
TI  - [Esophageal tuberculosis in an immunocompetent patient].
AB  - We present the case of a 68-year-old man who presented dysphagia and weight loss
      over the previous three months. Esophageal transit showed extreme stenosis
      suspicious for neoplasia but which was revealed to be a granulomatous
      inflammatory lesion. Culture of the lesion revealed Mycobacterium tuberculosis.
      Chest x-ray showed pulmonary tuberculosis. Esophageal tuberculosis should be
      considered in patients with dysphagia and pulmonary tuberculosis.

PMID- 14670240
TI  - [Clinical management of acute colonic pseudo-obstruction in patients: a
      systematic review of the literature].
AB  - Intestinal pseudoobstruction is a clinical syndrome characterized by impairment
      of intestinal propulsion, which may resemble intestinal obstruction, in the
      absence of a mechanical cause. It usually affects the colon but the small
      intestine may also be involved, and may present in acute, subacute or chronic
      forms. We have performed a systematic review of the acute form of
      pseudoobstruction, also referred to as Ogilvie's syndrome. We discuss proposed
      pathophysiological mechanisms, manifestations and management of this clinical
      condition in post-surgery and critically ill patients. The hallmark of the
      syndrome is massive intestinal distension, which is detected on clinical
      inspection and plain abdominal radiography. The underlying pathophysiological
      mechanisms are not fully understood. Therefore, treatment has focussed on
      preventing intestinal perforation, which is associated with a 21% mortality rate.

PMID- 14670241
TI  - [Microsatellite instability in colorectal cancer: concept, detection methods and
      clinical utility].

PMID- 14670242
TI  - [Zolmitriptan-induced hepatotoxicity].

PMID- 14670243
TI  - [Esophageal epidermoid carcinoma after sclerosis of esophageal varices].

PMID- 14670244
TI  - [Giant hepatic adenoma not associated with oral contraceptive intake].

PMID- 14670245
TI  - [Perforation of the transverse colon in closed abdominal trauma: lesion caused by
      safety belt].

PMID- 14670246
TI  - [Atypical presentation of infectious mononucleosis: diarrhea and rectorrhagia].

PMID- 14670247
TI  - [The role of patient classification systems in the financing of hospital
      emergencies].

PMID- 14670248
TI  - [To our reviewers, with love].

PMID- 14670251
TI  - [Incidence of invasive pneumococcal disease in Cantabria, Spain, [1995-2001] and
      implications for the childhood inmunization schedule].
AB  - OBJECTIVE: To describe the incidence of invasive pneumococcal disease in
      Cantabria (Spain) between 1995 and 2001. METHOD: We reviewed the records of the
      Minimum Data Set (MDS) of public hospitals in Cantabria, discharges from private
      hospitals and the registry of diseases of mandatory reporting, as well as the
      microbiologic diagnoses and medical records of children discharged from the
      Pediatric Service of the Cantabria Hospital (the tertiary care hospital in our
      autonomous community). RESULTS: We obtained a meningitis incidence of 5.55, 5.03
      and 0.76/100,000 in children < 2 years, > or = 2 and < 5 years, and > or = 5
      years respectively, and an incidence of invasive disease of 11.11, 11.32 and
      1.49/100,000 in the same age groups. CONCLUSIONS: The incidence of meningitis and
      invasive pneumococcal disease in Cantabria is low. We discuss factors that should
      be taken into account when introducing the pneumococcal conjugate vaccine in the
      childhood immunization schedule of Cantabria.

PMID- 14670250
TI  - [Analysis and classification of hospital emergencies through Ambulatory Patient
      Groups].
AB  - AIM: To assess the feasibility and results of application of Ambulatory Patient
      Groups (APG) patient's classification system to the case-mix of patients seen at
      the Emergency Departments (ED) of 6 Barcelona metropolitan area hospitals.
      METHODS: Development of a minimum discharge data set specific for the Emergency
      Departments (CMBDAU). Gathering of relevant variables from a random sample of
      patients seen at the ED using the ED discharge reports. Use of the APG
      classification system to those episodes. RESULTS: A total of 11.188 episodes were
      codified and grouped with the APG system. Fifteen diagnostics identified 25% of
      all episodes. Nearly 50% of all procedures performed at the ED were common and
      simple procedures. Fifteen APG's grouped 50% of all cases seen at the ED.
      CONCLUSIONS: The ED Uniform Discharge Data Set (CMBDAU) developed is a valid
      instrument for describing the case-mix seen at the ED, and its grouping by means
      of the APG system provides consistent and meaningful results. The widespread use
      of systems like APG in the ED requires a former validation of relative weights
      assigned in the US system. The availability of human and technical resources must
      also be assessed, in order to guarantee the quality and sustainability of such a
      system.

PMID- 14670252
TI  - [Invasive pneumococcal disease in children in the Community of Valencia, Spain].
AB  - OBJECTIVE: Pneumococcal disease is an important cause of morbidity and mortality
      in children. The recent authorization of the heptavalent conjugate vaccine has
      increased interest in this disease. The objective of this study was to identify
      the epidemiological and clinical characteristics of this disease, as well as its
      outcome in the pediatric population of the Autonomous Community of Valencia.
      METHOD: Data were obtained from the medical records of children aged less than 15
      years who were positive for pneumococcus isolation on admission to hospital
      between 1996 and 2000. All the public hospitals of the Autonomous Community of
      Valencia were included. Changes in incidence were evaluated by comparing rates
      and outcomes (sequelae and lethality) through frequency and age distribution.
      RESULTS: One hundred twenty-seven cases were registered, giving a mean annual
      rate of 3.89/105 inhabitants aged less than 15 years. The rate was 20.14 in
      children aged less than 2 years. A total of 29.1% of the children had previous
      health problems. The main clinical manifestations included sepsis/bacteremia
      (38%), pneumonia (31%) and meningitis (24%). At discharge sequelae were present
      in 10 children, 75% of whom were aged less than 2 years. Eight children died
      (6.3% lethality). CONCLUSIONS: In the period and region studied, pneumococcal
      infection was present mainly in children aged less than 2 years and in those with
      previous health problems. In the last few years, mortality has increased. Thus,
      inclusion of pneumococcal disease in the epidemiological surveillance system
      would be appropriate to achieve more precise estimations of its epidemiological
      patterns and to determine whether the conjugate vaccine represents a solution to
      the problems currently associated with this bacteria.

PMID- 14670253
TI  - [Trends in mortality and years of life lost related to alcohol in the Canary
      Islands, Spain [1980-1998]].
AB  - OBJECTIVE: The aim of this article was to describe death rates and years of life
      lost prematurely (YLLP) in relation to alcohol consumption in the Canary Islands.
      The study covered the period between 1980 and 1998. METHODS: Deaths from 1980 to
      1998 were classified by age, sex, and cause using data obtained from the National
      Institute of Statistics (Natural Changes in the Population). The number of
      alcohol-related deaths was calculated by year, sex, and age group using the
      attributable population fraction as proposed by the Centers for Disease Control
      (USA). The YLLP attributed to alcohol consumption were calculated for each cause
      of death by multiplying deaths by the attributable population fraction in 5
      yearly age groups for both sexes (average span of five years), up to the age of
      65 years. RESULTS: Between 1980 and 1998, the number of alcohol-related deaths
      was 12,614, averaging 6.4% per year and with a male-to-female ratio of
      approximately 2:1. The main causes of death and YLLP in both men and women were
      malignant neoplasms, diseases of the digestive system, and alcohol-related
      accidents, although accidents were by far the main cause producing 50.6% of
      alcohol-related YLLP in men and 55.5% in women. Over the study period, the
      incidence of cirrhosis of the liver and that of other chronic liver diseases (CIE
      571) decreased in men whilst remaining stable in women. CONCLUSIONS: The finding
      that the percentage of alcohol-related deaths and cirrhosis of the liver remained
      high in the Islas Canarias between 1980 and 1998 highlights the need for
      educational strategies on the effects of alcohol, together with policies designed
      to reduce its consumption, particularly among the young.

PMID- 14670254
TI  - [Imputation of the date of HIV seroconversion in cohorts of haemophiliacs].
AB  - OBJECTIVES: To describe the methods used to impute HIV seroconversion date in the
      haemophiliac cohorts from GEMES project and to validate its use. METHOD: 632
      haemophiliacs coming from three hemophilia units identified as HIV+ and 1.092
      individuals coming from 5 project GEMES cohorts with a seroconversion window
      (time among test HIV and HIV+) less than 3 years where mid point (PM) was assumed
      as seroconversion date. For both groups, seroconversion date was imputed after
      estimating the probability distribution of seroconversion by means of the EM
      algorithm. Two imputation methods are used: one obtained from the expected value
      and the other from the geometric mean of 5 random samples. from the estimated
      distribution. Imputations have been validated in the non haemophiliacs cohorts
      comparing with the PM seroconversion date. Also AIDS free time and survival from
      the different seroconversion imputed dates were compared. RESULTS: Median
      seroconversion date is located in May of 1993 for the non haemophiliacs and in
      1982 for the haemophiliacs. Not big differences are observed among the imputed
      seroconversion dates and the mid-point seroconversion date in the non
      haemophiliac cohorts. Similar results are found for the haemophiliac cohorts.
      Also no differences are observed in the estimated AIDS-free time for both groups
      of cohorts. CONCLUSIONS: Geometric mean imputation from several random samples
      provides a good estimate of the HIV seroconversion date that can be used to
      estimate AIDS-free time and survival in haemophiliac cohorts where seroconversion
      date is ignored.

PMID- 14670255
TI  - [Influence of burnout on pharmaceutical expediture among primary care
      physicians].
AB  - OBJECTIVE: To determine the influence of various factors related to primary care
      physicians and their level of burnout on pharmaceutical expenditure per policy
      holder (PEP-H). METHOD: We performed a cross-sectional study of 220 primary care
      physicians in the province of Barcelona in 2000. A structured and validated
      questionnaire was administered through direct interview. The questionnaire was
      divided into two parts: general sociodemographic and professional data, and the
      Maslach Burnout Inventory (MBI). At the same time, data on primary care
      physicians' pharmaceutical expenditure was collected from their corresponding
      health districts. RESULTS: The mean pharmaceutical expenditure was 264,627.22
      euros (95% CI, 252,669.82-276,584.63) and the PEP-H was 152,36 euros (95% CI,
      145,73-158,99). The variables associated with greater PEP-H were older age of the
      primary care physician, greater number of years of service in primary care,
      permanent work contract, primary care physicians who worked in several centers at
      the same time, primary care physicians who did not work in accredited teaching
      centers, urban centers, and high levels of emotional exhaustion in the MBI.
      CONCLUSIONS: Primary care physicians are subject to various degrees of stress in
      their daily work. Accumulation of these psychological stressors provokes
      emotional exhaustion, which complicates decision making when writing
      prescriptions and tends to lead to a vicious circle. Thus, primary care
      physicians with a high level of burnout could, on a variety of occasions,
      compensate for this lack of psychological resources by less efficient management
      of pharmaceutical expenditure when prescribing.

PMID- 14670256
TI  - [Impact of a smoke-free workplace policy in a company].
AB  - OBJECTIVE: To assess the impact of a smoke-free workplace policy in a company.
      METHOD: The impact of the implementation of a smoke-free workplace policy was
      assessed between October 2001 and February 2003 in a company with 184 employees.
      Two surveys of the entire staff were performed, one before the implementation of
      the new policy and the other 14 months after. RESULTS: Both passive exposure to
      tobacco smoke and tobacco consumption among smokers decreased. The proportion of
      workers free of tobacco smoke exposure at their workplace increased from 32% to
      84% (p < 0.001) and, among smokers, the mean daily consumption of cigarettes was
      reduced by 7.3 cigarettes (p = 0.049). CONCLUSIONS: Demarkation of areas where
      smoking is allowed not only reduces passive exposure to tobacco smoke at the
      workplace but also seems to encourage smokers to quit smoking or to reduce
      tobacco consumption.

PMID- 14670257
TI  - [Liability for medical malpractice: an economic approach].
AB  - In recent years, changes in the organization of healthcare institutions and the
      increased number of medical malpractice claims have revealed the need to study
      the concept of medical responsibility and the repercussion of these changes on
      healthcare provision. To date, discussion has focussed on legal aspects and
      economic implications have been largely ignored.The present article reviews
      studies that have performed an economic analysis the subject. Firstly, we examine
      studies that gradually introduce the concepts of uncertainty, risk aversion and
      moral hazard. Secondly, in the healthcare environment, we pay particular
      attention to models that include new arguments on professionals' objective duties
      or to bargaining models when there is asymmetric information. Finally, we
      consider the medical malpractice insurance market and investigate how reputation
      and the possibilities of exercising defensive medicine influence healthcare
      provision. Our analysis suggests that, due to the characteristics of the
      healthcare market, the models proposed by the economy of information are very
      useful for performing economic analyses of liability in medical malpractice.
      However, alternative hypotheses also need to be formulated so that these models
      can be adapted to the specific characteristics of different health systems.

PMID- 14670258
TI  - [Application of artificial neural networks for risk stratification of hospital
      mortality].
AB  - OBJECTIVE: To compare the ability of an artificial neural network (ANN) to
      predict hospital mortality with that of the Acute Physiology and Chronic Health
      Evaluation II (APACHE II) system and multiple logistic regression (LR). A
      secondary objective was to compare the allocation of individual probability among
      the models. METHOD: The variables required for calculating the APACHE II were
      prospectively collected. A total of 1146 patients were divided (randomly 70% and
      30%) into the Development (800) and the Validation (346) sets. With the same
      variables an LR model and an ANN were carried out (a 3-layer perceptron trained
      by algorithm backpropagation with bootstrap resampling and with 9 nodes in the
      hidden layer) in the Development set. The models developed were contrasted with
      the Validation set and their discrimination properties were evaluated using the
      area under the ROC curve (AUC [95% CI]) and calibration with the Hosmer-Lemeshow
      C (HLC) test. Differences between the probabilities were evaluated using the
      Bland-Altman test. RESULTS: The Validation set showed an APACHE II with an AUC =
      0.79 (0.75-0.84) and HLC = 11 (p = 0.329); LR model AUC = 0.81 (0.76-0.85) and
      HLC = 29 (p = 0.0001) and an ANN AUC = 0.82 (0.77-0.86) and HLC = 10 (p = 0.404).
      The patients with the most important differences in the allocation of probability
      between LR and ANN (8% of the total) were neurological. The worst results were
      found in trauma patients with an AUC of not greater than 0.75 in all the models.
      In respiratory patients, the ANN achieved the best AUC = 0.87 (0.78-0.91).
      CONCLUSIONS: The ANN was able to stratify hospital mortality risk by using the
      APACHE II system variables. The ANN tended to achieve better results than LR,
      since, in order to work, it does not require lineal restrictions or independent
      variables. Allocation of individual probability differed in each model.

PMID- 14670259
TI  - [Review of ethical aspects in biomedical research. The experience of the Ethics
      Committee of the Center for Toxic Oil Syndrome and Rare Diseases [CISATER]].
AB  - This Field Note aims to make known the decisions taken by the Ethics Committee of
      the Instituto de Salud Carlos III for Toxic Oil Syndrome regarding the secondary
      use of research specimens in biological research when informed consent is
      lacking. This is a common concern in the field of biomedical research. After
      debating the ethical suitability of the secondary use of these samples, our main
      conclusion is that researchers conducting prospective studies should expressly
      solicit written informed consent from participants in the study about i) whether
      there will or could be any secondary use of the samples and, if so, ii) whether
      such secondary use would be conditional on the type of research.

PMID- 14670260
TI  - [From the municipal dog pound to the pet shelter in Barcelona, Spain].
AB  - This article aims to present changes in public health policy and services related
      to pet dogs and cats in the city of Barcelona from 1983 to 2001. Initially the
      center's activity was limited to the custody and euthanasia of stray animals,
      serving not only the city but also the rest of the province. With the formulation
      of a city Plan for Pet Animals, the activities were redirected, concentrating on
      services within the city limits and stimulating adoption. Participation of both
      professional and humane organizations was sought, premises were renovated,
      responsible ownership of animals was promoted, controlled urban colonies of cats
      were established, and adoptions become the cornerstone of policy, centering the
      activity of the shelter toward its clients. Changes in the shelter's activity
      since 1998 reflects a clear decrease in the number of animals retained, as well
      as in the proportion subjected to euthanasia. This decrease may reflect an
      improvement in the problem of stray animals. These developments have also
      resulted in a positive change in the relationship with the media and animal
      welfare organizations.

PMID- 14670261
TI  - [Warning systems: a priority in epidemiological surveillance].
AB  - One of the functions of public health is to reduce the impact of emergency
      situations; hence the need to establish an early warning and response system.
      Community reactions to emerging and reemerging diseases, exposure to
      environmental risks, and potential terrorist acts are the factors that have that
      have mainly contributed to the instauration of warning systems based on
      mathematical models. Information is obtained from diverse sources (for example,
      laboratory data, sentinel physicians, or visits to particular websites). Once the
      data are gathered, and the situation provoking the alert is detected, control
      measures to reduce risks and minimize damage are taken at the earliest.

PMID- 14670263
TI  - [Smoking and lung cancer in Asturias, Spain].

PMID- 14670265
TI  - [Septal ablation in hypertrophic cardiomyopathy: current status].

PMID- 14670266
TI  - [From multicenter trial to national registries: the truth about the management of
      myocardial infarction].

PMID- 14670267
TI  - [Indication of automatic implantable defibrillator after primary percutaneous
      transluminal coronary angioplasty].

PMID- 14670268
TI  - [Management of myocardial infarction in Spain in the year 2000. The PRIAMHO II
      study].
AB  - INTRODUCTION AND OBJECTIVES: Hospital registries are useful tools to measure the
      degree of implementation of new treatments and clinical practice guidelines.
      PATIENTS AND METHOD: The hospital registry described here was developed in the
      prospective PRIAMHO II study, which involved a random selection of Spanish
      hospitals with a coronary intensive care unit and external quality control. This
      study investigated patients admitted to the coronary care unit with acute
      myocardial infarction. Demographic and clinical characteristics were recorded, as
      well as the management, clinical course and survival after 28 days and one year.
      RESULTS: From May 15 to December 15 2000 we included in the registry 6,221
      patients from the 58 hospitals that complied with the quality control
      requirements (71.6% of all participating hospitals). Acute mortality was 9.6%; 28
      day and one-year mortality were 11.4% and 16.5%, respectively. Of the patients
      with ST elevation-myocardial infarction of less than 12 hours' duration, 71.6%
      were reperfused and 89.3% received fibrinolysis with a median door-to-needle time
      of 48 minutes. Ejection fraction was measured in 81% of the patients, and 43%
      were tested for inducible ischemia. About nine-tenths (91%) of the patients were
      discharged on least one antiplatelet drug, 56% on a beta blocker, 45% on an ACE
      inhibitor, and 45% on a lipid-lowering agent, with a coefficient of variation
      between hospitals greater than 25% for the last three drugs. CONCLUSIONS: The
      percentage of patients with ST elevation treated with reperfusion should
      increase, as it probably will thanks to the increasing use of primary
      angioplasty. The door-to-needle time was longer than the recommended interval. In
      hospital risk stratification was good but nonsystematic for the evaluation of
      ejection fraction, and unsatisfactory for inducible ischemia testing. At
      discharge the percentages of patients receiving beta blockers, ACE inhibitors and
      statins were not optimal, and there were wide variations in prescribing practices
      between hospitals.

PMID- 14670269
TI  - [Left ventricular remodeling in patients with hypertrophic obstructive
      cardiomyopathy treated with percutaneous alcohol septal ablation: an
      echocardiographic study].
AB  - INTRODUCTION: In patients with hypertrophic obstructive cardiomyopathy,
      obstruction in the left ventricular outflow tract may generate more hypertrophy.
      Our aim was to evaluate the impact of reducing ventricular outflow tract
      obstruction on left ventricular hypertrophy and remodeling after alcohol septal
      ablation. PATIENTS AND METHOD: 20 patients with hypertrophic obstructive
      cardiomyopathy who underwent alcohol septal ablation were included. Doppler
      echocardiography was performed in all patients at baseline, immediately after
      alcohol septal ablation, and at 3 and 12 months' follow-up. Left ventricular
      diameters and wall thickness and pressure gradients in the ventricular outflow
      tract were determined. RESULTS: Immediately after alcohol septal ablation,
      ventricular outflow tract pressure gradient decreased from 63.0 27.7 to 28.2 24.7
      mmHg (p < 0.001), without significant changes in left ventricular dimensions.
      However, after 12 months we observed an increase in left ventricular end
      diastolic (from 47.1 4.9 to 50.8 4.5 mm) and end-systolic diameter (from 27.1 3.0
      to 33.7 4.6 mm), as well as a reduction in septal (from 19.5 4.0 to 15.5 2.7 mm)
      and posterior wall thickness (from 14.0 2.2 to 12.9 1.3 mm) (p < 0.01 in all
      cases). Left ventricular end-diastolic and end-systolic volumes increased (from
      106.4 26.9 to 123.1 28.7 ml and from 50.2 17.3 to 56.7 18.3 ml, respectively, p <
      0.01 in both cases), without changes in left ventricular ejection fraction. The
      reduction in ventricular outflow tract pressure gradient at 12 months' follow-up
      correlated significantly with the increase in left ventricular end-systolic
      diameter (r = 0.63; p < 0.01). CONCLUSIONS: In patients with hypertrophic
      obstructive cardiomyopathy who underwent alcohol septal ablation, relief of
      ventricular outflow tract obstruction is associated with an increase in left
      ventricular chamber diameters and volume. These findings suggest that middle- and
      long-term ventricular remodeling and regression of hypertrophy occur in these
      patients, which may contribute to their clinical improvement.

PMID- 14670270
TI  - [Impact of primary angioplasty on the indication for implantable cardiac
      defibrillator in patients with myocardial infarction].
AB  - INTRODUCTION AND OBJECTIVES: Implantable cardiac defibrillators (ICD) have been
      shown to improve survival in patients with myocardial infarctionand LVEF < 0.30
      or LVEF < 0.40 + nonsustained ventricular tachycardia + inducible sustained
      arrhythmias. However, these risk stratification criteria have not been evaluated
      in patients who are candidates for primary percutaneous transluminal coronary
      angioplasty (PTCA). The objective of this study was to assess the impact of both
      strategies on the indication for ICD in a consecutive series of post-infarction
      patients treated with primary PTCA. PATIENTS AND METHOD: One hundred and two
      consecutive patients with myocardial infarction (80 men, mean age 63.6 11.5
      years) included in a single-center-based regional program of primary PTCA were
      included in the study. A 24-h continuous ECG recording was obtained 2 to 6 weeks
      after the acute event, and LVEF was determined by 2D-echocardiography one month
      after the infarct. Patients with nonsustained ventricular tachycardia and LVEF <
      0.40 underwent programmed ventricular stimulation using a standard protocol.
      RESULTS: Twenty-two patients (21.6%; 95% CI, 13.6-29.6) showed at least one
      episode of nonsustained ventricular tachycardia in the 24 h recording. Six of
      them had LVEF < or = 0.40, and sustained ventricular arrhythmia was induced in 2
      out of 5. LVEF < or = 0.30 was found in 3 patients, none of whom had nonsustained
      ventricular tachycardia. Thus, 5 patients had an indication for ICD according to
      either of the two risk stratification criteria. CONCLUSIONS: The prevalence of
      nonsustained ventricular tachycardia in post-infarction patients treated with
      primary PTCA is high. However, because most of them have preserved ventricular
      function, primary prevention with an ICD is indicated in approximately 5% of the
      population.

PMID- 14670271
TI  - [Patterns of clinical presentation of atrial fibrillation in hospitalized
      patients].
AB  - INTRODUCTION AND OBJECTIVES: The ACC/AHA/ESC 2001 guidelines for the management
      of atrial fibrillation (AF) establish 4 categories: first episode, paroxysmal,
      persistent and permanent. The aim of this study was to analyze the frequency of
      the different clinical patterns of presentation of AF in hospitalized patients.
      PATIENTS AND METHOD: We analyzed the pattern of AF in 300 hospitalized patients,
      200 of whom were admitted to the cardiology and 100 to the internal medicine
      department. We determined the clinical profile and evaluated the factors
      influencing therapeutic management. RESULTS: The permanent form was present in
      30% of the patients admitted to the cardiology department and in 51% if those
      admitted to the internal medicine department. The first episode pattern was the
      most frequent in cardiology department patients (41%). In patients hospitalized
      the in cardiology the percentage use of anticoagulants (57.9% vs. 41%; p < 0.01)
      and beta blockers was greater than in internal medicine patients, and digitalis
      use was lower. In the multivariate analysis, admission to the cardiology
      department was an independent predictor of treatment with beta blockers (OR =
      3.8; 95% CI, 1.3-11.1; p < 0.05), and discharge from the hospital with AF was a
      predictor of anticoagulant prescription (OR = 4.8; 95% CI, 2.5-9.2; p < 0.001).
      CONCLUSIONS: a) Atrial fibrillation is an arrhythmia with a heterogeneous
      clinical pattern that varies depending on the type of care provided; b) on
      admission to cardiology, only 30% of the patients present with permanent
      arrhythmia, and the most frequent clinical pattern is first episode; and c)
      discharge from the hospital with AF was the principal determinant of therapeutic
      management.

PMID- 14670272
TI  - [Diagnostic performance of echocardiography in the follow-up of patients with
      toxic oil syndrome].
AB  - INTRODUCTION AND OBJECTIVES: Toxic oil syndrome is an epidemic, multisystemic
      disease that appeared in Spain in 1981, and was caused by the consumption of
      rapeseed oil denatured with 2% aniline. The disease is similar to eosinophilia
      myalgia syndrome. One of the cardiovascular disorders caused by this syndrome is
      pulmonary hypertension. We conducted a study to assess the validity of our
      indications for echocardiography in the follow-up of cardiovascular disorders in
      patients with this disease. PATIENTS AND METHOD: These patients are followed at
      our center with a standardized protocol for annual check-ups. From December 1997
      through July 2002, a total of 1993 patients were examined. In this period we
      performed a total of 487 echocardiographic studies in 424 patients. The clinical
      records were reviewed to assess the indications for echocardiography according to
      the most recent guidelines for the clinical application of echocardiography of
      the American College of Cardiology and American Heart Association, and the
      indications were grouped into several categories. The diagnosis was recorded from
      the cardiologist's reports at the hospital where echocardiography was done. We
      calculated the sensitivity, specificity and positive likelihood ratio. RESULTS:
      67% of the echocardiographic examinations were indicated to investigate possible
      pulmonary hypertension. About one-tenth of the studies (476 studies, 9.9%) led to
      a diagnosis of pulmonary hypertension. Sensitivity was highest (83%) for
      suspected pulmonary hypertension. Specificity was very high for most of the other
      indications. CONCLUSIONS: This study does not allow us to draw general
      conclusions about the cardiovascular disorders associated with toxic oil
      syndrome. However, echocardiography appears to be a good follow-up technique to
      diagnose complications such as pulmonary hypertension in these patients.

PMID- 14670273
TI  - [The vascular smooth muscle of great arteries: local control site of arterial
      buffering function?].
AB  - INTRODUCTION AND OBJECTIVES: To characterize the viscoelastic properties of the
      aorta and pulmonary arteries and the effects of vascular smooth muscle activation
      on arterial buffering function. MATERIAL AND METHOD: Aortic and pulmonary artery
      pressure and diameter were measured in six anesthetized sheep under baseline
      conditions, and during arterial hypertension induced by mechanical vascular
      occlusion (passive), and i.v. phenylephrine (active). Arterial wall elasticity
      and viscosity were calculated, and buffering function was characterized: a)
      locally as the viscosity/elasticity ratio, and b) globally for each circuit, as
      the time-constant of ventricular relaxation. RESULTS: Viscoelasticity was higher
      in the aorta than in the pulmonary artery (p < 0.05), however, parietal buffering
      function was similar in both. Global buffering function was highest in the
      systemic circuit (p < 0.05). During passive hypertension, elasticity was
      significantly increased with no change in viscosity; this led to a significant
      reduction in local buffering function, and in global buffering function in each
      circuit. During active hypertension, viscosity increased (p < 0.05), while local
      and global buffering functions returned to baseline values. CONCLUSIONS: The
      viscosity/elasticity ratio was higher in the aorta than in the pulmonary artery,
      and arterial wall buffering function was similar in both vessels. Systemic global
      buffering function was higher than pulmonary circuit buffering function.
      Elasticity depends on intravascular pressure, whereas viscosity is a marker of
      the degree of smooth muscle activation. Smooth muscle activation may benefit the
      cardiovascular system by maintaining local and global buffering functions.

PMID- 14670274
TI  - [Spanish Registry on Heart Transplantation. 14th official report of the working
      group on heart failure, heart transplantation and other therapeutic alternative
      of the Spanish Society of Cardiology (1984-2002)].
AB  - This report describes the general characteristics and outcomes of heart
      transplantation in Spain after data from 2002 were added to the registry. In
      2002, 310 heart transplantations were performed. Since 1984, a total of 4,096
      procedures have been performed. The average clinical profile of patients
      receiving a heart transplant in Spain is that of a man about 50 years old, blood
      group A, with nonrevascularizable coronary artery disease and functional status
      IV/IV (NYHA). The percentage of emergency heart transplantations was 26%, which
      is higher than the previous year (19%) and the mean for the preceding five years
      (22%). The early mortality rate was 10%, which is significantly lower than the
      mean for the preceding five years (14%). After combining the 2002 results with
      those of previous years, an increase in survival rate was seen. Thus, the
      probability of survival in the first, fifth and tenth years was 76%, 66%, and
      54%, respectively. When survival rates for separate periods were considered, a
      clear improvement was seen from the first year (80%) to the fifth year (72%). The
      most frequent causes of death were acute graft failure in the first month,
      infection and rejection in the first year, and tumors and the combination of
      vascular disease of the graft with sudden death in the long term. Comparative
      analysis of survival rates shows that our long-term results are slightly better
      than those published worldwide, with a clear tendency for survival rate to
      improve as a consequence of the experience acquired in all stages of this cross
      disciplinary procedure.

PMID- 14670275
TI  - [Assessment and therapeutic guideline of intermediate coronary lesions in the
      catheterization laboratory].
AB  - Contrast angiography has been used for nearly five decades to evaluate the
      severity of coronary lesions. However, when attempting to distinguish between
      intermediate coronary lesions able or unable to produce ischemia, the technique
      has several limitations. A large number of patients undergo cardiac
      catheterization without prior evaluation of coronary perfusion by non-invasive
      tests. This number is likely to increase in the coming years, because current
      recommendations favor the invasive treatment of acute coronary syndromes. This
      has triggered marked interest in new diagnostic techniques capable of assessing
      the physiological significance of intermediate lesions in the catheterization
      room. This paper reviews the different techniques currently available for
      scientifically assessing the significance of such lesions. The advantages and
      limitations of each are discussed.

PMID- 14670276
TI  - [Septal ablation in hypertrophic obstructive cardiomyopathy].

PMID- 14670277
TI  - [Occlusion of the first septal branch with microcoils in a patient with
      hypertrophic obstructive cardiomyopathy].
AB  - Nonsurgical septal reduction by induced septal infarction is one of the
      management options in the treatment of patients with hypertrophic obstructive
      cardiomyopathy. Good immediate and long-term clinical and hemodynamic results
      have been reported with this technique for occlusion of the first septal branch
      of the anterior descending coronary artery followed by ethanol infusion. This is
      the first report of a case in which nonsurgical septal reduction with microcoils
      has been attempted.

PMID- 14670278
TI  - [Pulmonary atresia with intact ventricular septum associated with severe aortic
      stenosis].
AB  - Pulmonary atresia with intact ventricular septum is the complete obstruction of
      the right ventricular outflow tract due to pulmonary valve atresia in the absence
      of ventricular septal defect. Pulmonary flow is dependent on the ductus
      arteriosus. Other morphological anomalies are also present. Aortic stenosis in
      association with pulmonary atresia with intact ventricular septum is extremely
      infrequent, and very few cases have been described. We report a 19-year-old
      primiparous woman in whom the fetal echocardiogram showed pulmonary atresia with
      intact ventricular septum. The neonate had low oxygen saturation and a systolic
      murmur originating in the aorta. An echocardiogram showed pulmonary atresia with
      intact ventricular septum and a bicuspid, thickened, stenotic aortic valve. Low
      cardiac output ensued and could not be controlled, and the infant died.

PMID- 14670279
TI  - [A high-quality international scientific journal on cardiovascular diseases].

PMID- 14670280
TI  - [Mitral valve prolapse is a frequent cardiovascular finding in patients with
      anorexia nervosa].

PMID- 14670283
TI  - Rhinitis as a precursor for asthma.

PMID- 14670284
TI  - Humoral immunity in pediatric patients with acute lymphoblastic leukaemia.
AB  - BACKGROUND: Cancer and its treatment are a major cause of secondary
      immunodeficiency in childhood. Leukaemias are the most frequent pediatric
      neoplastic diseases and 80 % are lymphoblastic (ALL). The objectives of this
      study are to describe the epidemiology of children with ALL in our hospital and
      to analyse the evolution of immunoglobulins' concentration at leukaemia's onset,
      during its treatment and after finishing it. METHODS AND RESULTS: Retrospective
      study of patients with ALL treated with the SHOP-LAL-94 protocol. 50 patients
      were studied. Patients were classified in three groups: ALL- cell line B, ALL
      cell line B with relapse, and ALL-cell line T. We analysed clinical data and
      laboratory results (IgG, IgA and IgM concentration) at leukaemia's onset, during
      its treatment and until 12 months after it.1. ALL-B: 44 patients. At the onset
      all patients, but a newborn with congenital leukaemia, had normal
      immunoglobulins. During treatment there was a significant decrease in
      immunoglobulins'concentration, being IgM the most affected (65 % of patients),
      followed by IgG (53 % of patients). The mean normalization time of
      immunoglobulins was 12 months.2. ALL-B with relapse: 7 patients. At relapse 2
      patients had an IgM deficit and 1 overall immunoglobulin deficiency. During
      treatment there was a decrease in all immunoglobulins, which was significant for
      IgG. IgG and IgM decreased in all patients during relapse's treatment. There were
      5 deaths, all with IgM < 186 mg/L.3. ALL-T: 6 patients, one died 3 days after
      diagnosis. At the onset all patients had normal immunoglobulins. Two patients had
      a favourable evolution, having a decrease in immunoglobulins'concentration during
      treatment, significant for IgM, with normalization 6 months after treatment. The
      rest 3 patients relapsed and died, having a global immunoglobulins'deficit during
      treatment and previous to death. CONCLUSIONS: At ALL's onset immunoglobulins'
      concentration is normal. During treatment the majority of patients have
      immunoglobulins' deficiency, being IgG and IgM the most affected immunoglobulins.
      A persistent IgM deficit is associated in our series with a higher risk of
      relapse and death. In patients with a good outcome immunoglobulins normalize
      before one year after treatment.

PMID- 14670285
TI  - Detection of influenza, parainfluenza, adenovirus and respiratory syncytial virus
      during asthma attacks in children older than 2 years old.
AB  - BACKGROUND: Viral upper respiratory tract infections (URTI) have been correlated
      with the onset of asthma attacks in children and viral identification was
      reported in 14-49 % of nasal samples. The aim of the present study was to detect
      influenza, parainfluenza, adenovirus and respiratory syncytial virus (RSV) in
      older children during acute asthma attacks. METHODS: A total of 104 children (2
      14 years) were included in four groups: group I: asthmatics with acute attack and
      URTI; group II: asthmatics without URTI (group I children, 30 days later); group
      III: non-asthmatics with URTI; group IV: non-asthmatic, asymptomatic children. A
      diagnosis of URTI was considered when (3 symptoms (cough and/or sneeze, nasal
      obstruction, hypertrophy of turbinates, pain and/or retropharynx hyperemia,
      headache and fever) in asthmatics and at least 2 symptoms in non-asthmatics were
      present, starting within 7 days. Samples of nasal mucosa cells (n = 123) were
      collected, and culture and indirect immunofluorescence were carried out to
      identify respiratory syncytial virus, adenovirus, influenza A and B,
      parainfluenza 1,2 and 3 and rhinovirus. RESULTS: Viral identification rates were
      higher in the asthmatic groups: 13.9 % in group I, 11.1 % in group II; 2.8 % in
      group III and 0 in group IV. The following viruses were identified: RSV 2/36,
      rhinovirus 1/36, adenovirus 1/36 and parainfluenzae 1/36 in group I; adenovirus
      2/18 in group II; RSV 1/36 in group III. CONCLUSIONS: The rate of viral
      identification was higher in asthmatic children, whether symptomatic or not,
      suggesting a possible susceptibility to viral infections. Virus could also be a
      triggering factor in attacks, although it is not the most preponderant in older
      children.

PMID- 14670286
TI  - Does passive smoke exposure trigger acute asthma attack in children?
AB  - The relationship between asthma and passive smoking has been well established.
      However, it is still not clear whether an acute asthma attack can be induced by
      acute smoke exposure. The specific aims of this study were: 1- To assess the
      degree of smoke exposure through urinary cotinine levels in asthmatic children
      during and 4 weeks after asthma attacks and, 2- To evaluate the reliability of
      parental questionnaires in asthmatic children by comparing the data obtained from
      cotinine measurements and parental reports. Thirty-two consecutive asthmatic
      children who were admitted to the emergency clinic were included in the study.
      Parents were asked to complete a questionnaire about their smoking habits and
      housing conditions. Urinary cotinine and creatinine levels were measured in
      children during and 4 weeks after the acute asthma attack. The mean age of the
      patients was 5.7 +/- 3.2 years. The mean attack rate was 3.5 +/- 3.8 per year.
      Thirty-eight percent of the patients were taking no preventive treatment. In 80 %
      of patients, urinary cotinine and creatinine ratios (CCR) were significantly
      above the non-exposed, non-smoker levels. However, CCR levels during acute asthma
      attacks were not higher than those measured 4 weeks after the acute attack (314.6
      +/- 299.1 vs. 203.8 +/- 165.2 ng/mg respectively, p > 0.05). Although parental
      reports of passive smoke exposure was 71 %, CCR levels revealed that 81 % and 97
      % of children were exposed to passive smoke during acute attacks and asymptomatic
      periods, respectively. In conclusion, although the proportion of children with
      acute asthma attacks who were exposed to passive smoking was high, the degree of
      passive smoke exposure was not higher during acute attacks. Parental
      questionnaires were found to be unreliable in reporting passive smoke exposure in
      asthmatic children during acute attacks.

PMID- 14670287
TI  - Allergy to heparin: a new in vitro diagnostic technique.
AB  - INTRODUCTION: Few descriptions of allergic reactions to heparin have been
      published, because these reactions are not well known, their prevalence is low
      and they are difficult to diagnose due to the lack of an in vitro test until now.
      We propose a new technique, the basophil activation test (BAT) for the diagnosis
      of these reactions. METHODS AND RESULTS: We performed in vivo and in vitro
      studies with heparin and its derivatives in two patients with heparin-induced
      acute urticaria. In both patients the results of prick tests with sodium and
      calcium heparin, enoxaparin and nadroparin with immediate reading were negative.
      Intradermal skin tests with immediate reading and reading at 48 and at 96 hours
      with calcium heparin, enoxaparin and nadroparin were positive in the immediate
      reading and after 48 hours in the first patient. The second patient showed
      positivity to nadroparin in the immediate reading. The same drugs were also
      tested using patch tests, with reading after 48 and 72 hours. The second patient
      showed positivity to nadroparin after 48 hours. The BAT was positive to
      enoxaparin in the first patient and revealed showed slight positivity to sodium
      heparin in the second patient. CONCLUSIONS: We consider the BAT to be a useful,
      safe and reliable test for the in vitro diagnosis of heparin allergy. This test
      avoids the use of provocation tests, which present a risk to the patient.

PMID- 14670288
TI  - The efficacy of sublingual immunotherapy for respiratory allergy is not affected
      by different dosage regimens in the induction phase.
AB  - BACKGROUND: Sublingual administration of allergens is a safe and effective
      alternative to subcutaneous immunotherapy in patients with respiratory allergies.
      A drawback to this therapeutic approach is the relatively long and complex
      management of the induction phase. AIM OF THE STUDY: To determine whether
      different induction regimens affect the outcome of sublingual immunotherapy.
      METHODS AND RESULTS: Adult and pediatric patients with allergic
      rhinoconjunctivitis and/or asthma were included in the study. Ten subjects served
      as controls and received symptomatic treatments. Forty-three subjects were
      allocated to sublingual immunotherapy, with three different induction protocols
      (8-, 15- and 20-day, respectively). Symptom and medication scores, skin test
      results and (in asthmatic patients) FEV1 values were monitored for two years.
      Adverse effects were recorded. All induction regimens produced a significant
      improvement in symptom and medication usage (p < 0.0001); skin test scores
      decreased (p < 0.0001) and FEV1 improved (p < 0.05). In contrast, symptom and
      skin test scores did not significantly change in controls. No relevant adverse
      effects were observed with any of the induction regimens. CONCLUSIONS: For
      patients with respiratory allergies, sublingual immunotherapy with an 8-day
      induction protocol is safe and effective. Our results encourage the usage of
      shorter induction regimens, which produce better compliance with this therapy.

PMID- 14670289
TI  - Anaesthesia in aspirin-induced asthma.
AB  - The triad of bronchial asthma, nasal polyposis, and intolerance to aspirin and
      aspirin-like chemicals are designated aspirin-induced asthma (AIA) or Samter's
      syndrome. The exact mechanism of the disease is unknown but it is thought to be a
      disorder of arachidonic acid metabolism. These patients are frequently referred
      to allergy clinics for preoperative evaluation for possible anesthetic agent
      sensitivity, requiring anesthesia for nasal polypectomy or several other reasons.
      Anesthetists must be aware of their pulmonary dysfunction, because the anesthetic
      management of asthma requires a specific approach. Marked cross-sensitivity with
      NSAIDs, which may also precipitate severe bronchospasm and adverse reactions, is
      the main problem faced by anesthetists in postoperative pain management. This
      article discusses the relationship between AIA and anesthesia. We also present
      our experience with 47 patients diagnosed with AIA between 1991 and 2003 in the
      department of chest diseases and adult allergy unit who underwent surgery
      requiring general anesthesia. In conclusion, preoperative evaluation of these
      patients and collaboration between the allergists and anesthesiologists is
      essential to prevent preoperative, perioperative and postoperative complications.

PMID- 14670290
TI  - Anaphylactoid reaction to carboplatin: successful "desensitization".
AB  - Carboplatin (CP) hypersensitivity reactions have been reported in nearly 12 % of
      patients treated with this drug. The pathophysiologic mechanisms of these
      reactions have not been entirely elucidated. Various hypotheses are under
      discussion. CP hypersensitivity reactions could be IgE-mediated, caused by low
      molecular platinum compounds acting as haptens. Platinum salts are also able to
      release histamine from basophils and mast cells, and some events seem to be non
      immune-mediated direct histamine release. We report a case of CP tolerance
      induction in a 65-year-old man. During the third course of CP he experienced an
      anaphylactic reaction. Skin testing was negative. Suspecting the possibility of
      an anaphylactoid reaction due to histamine release, we developed a protocol to
      induce tolerance. Pre-medication with corticosteroid and antihistaminic was
      performed before intravenous CP infusion. The bag with CP was first infused 60
      ml/h for 30 minutes; the infusion was well tolerated and infusion was continued
      at 100 ml/h for the next 60 minutes and thereafter at 120 ml/h until the bag was
      finished. Following this "desensitization", monthly courses of CP using the same
      protocol have been well tolerated.

PMID- 14670291
TI  - Anaphylaxis to oral furosemide.
AB  - Furosemide, one of the most used diuretic drugs, rarely induces type-1 allergic
      reactions It is included in the non-aromatic sulfonamides but a cross-reactivity
      mechanism between this group and the sulfonamides antibiotics, has not been
      clearly demonstrated. A 24-year-old woman, 10 minutes after the intake of one
      pill of Seguril 40mg experienced oral itching, generalized urticaria, facial
      angioedema, dyspnea and hypotension. She recovered after the administration of
      parental adrenaline, methyl-prednisolone and dyphenhydramine. An skin prick test
      with furosemide (10 mg/ml) was negative. The intradermal skin tests were positive
      to furosemide (1 %) as well as sulfamethoxazole (0.03 mg/ml), with 10 atopic and
      non-atopic negative controls. The patient rejected the performance of an oral
      challenge test with sulfamethoxazole. IgE-mediated reactions to furosemide are
      infrequent, but it could be the cause of life-threatening reactions. We have
      reported a case of anaphylaxis after the oral administration of furosemide with a
      demonstrated hypersensitivity mechanism through the positive intradermal skin
      test. The previous administration of the drug could probably the mechanism of
      sensitization, but the positive intradermal test to sulfamethoxazole would open
      the hypothesis of a cross-reactivity between non-aromatic and antimicrobial
      sulfonamides. It could be necessary an oral challenge test with furosemide in
      allergic patients to sulfamides.

PMID- 14670293
TI  - Serine phosphorylation: arming Stat1 against infection.
AB  - A powerful weapon is critical to a soldier when battling with a strong enemy. In
      this issue of Immunity, Varinou et al. suggest that serine phosphorylation of
      Stat1, an important signal transducer and activator of transcription in
      interferon (IFN) signaling, is required for Stat1 to fight against a highly
      pathogenic infection.

PMID- 14670292
TI  - [Anisakis and anisakiosis].
AB  - The nematode Anisakis simplex (AS) is a world wide distributed parasite that
      infects consumers of raw or undercoocked parasitized fish. The clinical
      manifestation of Anisakiosis depend on the site in the digestive tract in which
      larva lodges. The symptoms develops as a result of the inflammation when the
      larvae penetrates the gastric mucous. Most of asymptomatic subjects show high
      levels of specific IgE to AS. Diagnosis of AS allergy is not simple, due to cross
      reactivity with other allergens. In childhood is more difficult to make a right
      diagnosis than in adult population. Most of positive prick test to AS correspond
      to children with positive prick tests to other allergens. Cross-reactivity
      between this parasite and other parasites with a higher prevalence in childhood,
      is the cause of a false diagnosis. The secretor-excretory antigen shows a better
      specificity, recognizing the true parasitized patients. This antigen could be
      used as indicator of parasitization. To follow prevention rules AS, avoid
      consumption of raw fish unless frozen for 48 hours or ingestion of fresh fish
      always cooked for more than 20 minutes at least at 60 C.

PMID- 14670294
TI  - Molecular interactions: stiff or floppy (or somewhere in between?).
AB  - Recognition of MHC and MHC-like molecules by both natural killer (NK) and T cell
      receptors (TCR) reveals remarkable degeneracy. The interaction of the NKG2D NK
      receptor with several MHC I-like ligands has now been analyzed thermodynamically
      by McFarland and Strong, who suggest that a "rigid adaptation" mechanism governs
      such crossreactivity. This contrasts with "induced fit" that accounts for TCR
      adaptation to multiple MHCp ligands.

PMID- 14670295
TI  - Immunity and the animation of the genome.
AB  - Expression of genes in the right place at the right time is fundamental to all of
      life. The ontogeny of effector and memory T cells is a robust example of this
      important principle. Although lymphocytes represent a late addition in animal
      evolution, they are serving as an exceptional model system to unlock the
      mysteries surrounding the way in which the genome is animated. It will be
      speculated here that further insight into fundamental principles of genome
      function may arise from study of immunity. Likewise, such information may be key
      to understanding and altering immunobiology.

PMID- 14670296
TI  - Notch and the immune system.
AB  - Notch proteins are used repeatedly to direct developmental cell fate decisions in
      multiple organs. During hematopoiesis and immune development, Notch is critical
      for T/B lineage specification and for generation of splenic marginal zone B
      cells. In early embryonic development, Notch is crucial for generating
      hematopoietic stem cells. Emerging data suggest that Notch may also modulate the
      differentiation and activity of peripheral T cells. Understanding the specific
      regulation of the Notch pathway in different contexts and its interaction with
      other signaling pathways remains an important challenge to comprehend the full
      spectrum of Notch effects. In this review, we critically assess recent findings
      regarding the function of Notch in the hematolymphoid system.

PMID- 14670297
TI  - Phosphorylation of the Stat1 transactivation domain is required for full-fledged
      IFN-gamma-dependent innate immunity.
AB  - Stat1 is phosphorylated on serine 727 within its transactivating domain (TAD) in
      response to interferons or other immunological signals. We generated gene
      targeted mutant mice expressing a serine727-alanine mutant of Stat1. These
      animals showed increased mortality upon infection with Listeria monocytogenes and
      impaired clearance of the bacteria from spleen and liver. The Stat1S727A mice
      were more resistant to the LPS-induced septic shock syndrome, suggesting that
      Stat1 serine phosphorylation promotes inflammatory responses. Expression of IFN
      gamma-induced genes was strongly reduced in macrophages expressing Stat1(S727A).
      While mutation of Stat1 at S727 did not reduce its binding to chromatin,
      association with the coactivator CBP and histone acetylation at the interferon
      responsive GBP promoter was strongly reduced, suggesting defective recruitment of
      histone acetylases as the mechanism underlying IFN-gamma hyporesponsiveness. Our
      data demonstrate that the increase in transcription factor activity caused by
      Stat serine phosphorylation contributes to macrophage activation and to IFN-gamma
      dependent immune responses in vivo.

PMID- 14670298
TI  - Thermodynamic analysis of degenerate recognition by the NKG2D immunoreceptor: not
      induced fit but rigid adaptation.
AB  - The homodimeric immunoreceptor NKG2D drives the activation of effector cells
      following engagement of diverse, conditionally expressed MHC class I-like protein
      ligands. NKG2D recognition is highly degenerate in that a single surface on
      receptor monomers binds pairs of distinct surfaces on each structurally divergent
      ligand, simultaneously accommodating multiple nonconservative ligand allelic or
      isoform substitutions. In contrast to TCR-pMHC and other NK receptor-ligand
      interactions, thermodynamic and kinetic analyses of four NKG2D-ligand pairs (MIC
      A*001, MIC-B*005, ULBP1, and RAE-1beta) reported here show that the relative
      enthalpic and entropic terms, heat capacity, association rates, and activation
      energy barriers are comparable to typical, rigid protein-protein interactions.
      Rather than "induced-fit" binding, NKG2D degeneracy is achieved using distinct
      interaction mechanisms at each rigid interface.

PMID- 14670299
TI  - Negligible role of antibodies and C5 in pregnancy loss associated exclusively
      with C3-dependent mechanisms through complement alternative pathway.
AB  - Factors involved in pregnancy failure due to abnormal fetomaternal tolerance are
      poorly understood. Here we describe distinct defects in placenta formation and
      subsequent pregnancy loss solely dependent on the activation of the complement
      alternative pathway and the effector mechanisms provided by the maternal C3.
      Surprisingly, this effect is independent of other complement activation pathways
      and of the effector mechanisms provided by other complement components. These
      findings provide significant insight into the role of the innate immune system in
      human pregnancy failure, a frequent clinical outcome.

PMID- 14670300
TI  - CD40, but not CD40L, is required for the optimal priming of T cells and control
      of aerosol M. tuberculosis infection.
AB  - CD40(-/-) mice succumbed to low-dose aerosol infection with M. tuberculosis due
      to deficient IL-12 production leading to impaired priming of IFN-gamma T cell
      responses. In contrast, CD40L(-/-) mice were resistant to M. tuberculosis. This
      asymmetry in outcome of infection between the two knockout strains is likely due
      to the existence of an alternative ligand for CD40. Both in vitro M. tuberculosis
      infection and recombinant M. tuberculosis Hsp70 elicited IL-12 production from WT
      dendritic cells. This response was absent in both CD40(-/-) dendritic cells and
      CD40(-/-) mice, suggesting that M. tuberculosis Hsp70 serves as an alternative
      ligand for CD40 in vivo.

PMID- 14670301
TI  - Activation of autoreactive B cells by CpG dsDNA.
AB  - The proliferative response of autoreactive rheumatoid factor (RF) B cells to
      mammalian chromatin-containing immune complexes (ICs) results from the sequential
      engagement of the B cell receptor (BCR) and Toll-like receptor 9 (TLR9). We have
      used ICs constructed from anti-hapten antibodies and defined haptenated dsDNA
      fragments to determine the form of mammalian DNA that mediates this process.
      Despite their relatively low abundance in mammalian DNA, we found that inclusion
      of hypomethylated CpG motifs in these ICs was necessary for effective activation.
      In the absence of antibody, the same fragments could efficiently stimulate low
      affinity hapten-specific and DNA-reactive 3H9 B cells, but not RF B cells. These
      results extend the BCR/TLR9 coengagement paradigm to a second major class of
      autoreactive B cells, further confirm the critical role of the BCR in chromatin
      ligand delivery to TLR9, and implicate hypomethylated CpG motifs as ligand
      elements necessary for the initiation of systemic autoimmune disease.

PMID- 14670302
TI  - Colonic dendritic cells, intestinal inflammation, and T cell-mediated bone
      destruction are modulated by recombinant osteoprotegerin.
AB  - Autoimmune associated bone disease and intestinal inflammation are closely linked
      with deregulation and hyperactivation of autoreactive CD4 T cells. How these T
      cells are activated and mediate disease is not clear. Here we show that in the
      Interleukin 2-deficient mouse model of autoimmunity spontaneous osteopenia and
      colitis are caused by increased production of the ligand for receptor activator
      of NFkappaB (RANKL). RANKL acting via its receptor, receptor activator of
      NFkappaB (RANK), increases bone turnover and promotes intestinal dendritic cell
      (DC) survival in vivo. Modulation of RANKL-RANK interactions with exogenous
      recombinant osteoprotegerin (Fc-OPG) reverses skeletal abnormalities and reduces
      colitis by decreasing colonic DC numbers. This study identifies a common causal
      link between bone disease and intestinal inflammation and establishes the
      importance of DC in mediating colonic inflammation in vivo.

PMID- 14670303
TI  - Critical roles for transcription factor GATA-3 in thymocyte development.
AB  - The transcription factor GATA-3 is expressed at every stage of thymic
      development, but its role in thymocyte differentiation is unknown. The fact that
      RAG chimeric animals lacking GATA-3 cannot generate early thymocytes from common
      lymphoid progenitors has thus far precluded investigation of the function of GATA
      3 in the thymus. To address this, we generated mice deficient in GATA-3 at early
      and late stages of thymic differentiation. Our studies revealed that GATA-3 is
      involved in beta selection and is indispensable for single-positive CD4 thymocyte
      development. Thus, our data demonstrate that the coordinated and regulated
      expression of GATA-3 at each stage of thymic development is critical for the
      generation of mature T cells.

PMID- 14670304
TI  - CD40 ligation releases immature dendritic cells from the control of regulatory
      CD4+CD25+ T cells.
AB  - We report that disruption of CD154 in nonobese diabetic (NOD) mice abrogates the
      helper function of CD4+CD25- T cells without impairing the regulatory activity of
      CD4+CD25+ T cells. Whereas CD4+ T cells from NOD mice enhanced a diabetogenic
      CD8+ T cell response in monoclonal TCR-transgenic NOD mice, CD4+ T cells from
      NOD.CD154(-/-) mice actively suppressed it. Suppression was mediated by
      regulatory CD4+CD25+ T cells capable of inhibiting CD8+ T cell responses induced
      by peptide-pulsed dendritic cells (DCs), but not peptide/MHC monomers. It
      involved inhibition of DC maturation, did not occur in the presence of CD154+ T
      helper cells, and could be inhibited by activation of DCs with LPS, CpG DNA, or
      an agonistic anti-CD40 mAb. Thus, in at least some genetic backgrounds, CD154
      CD40 interactions and innate stimuli release immature DCs from suppression by
      CD4+CD25+ T cells.

PMID- 14670305
TI  - Sequential MyD88-independent and -dependent activation of innate immune responses
      to intracellular bacterial infection.
AB  - Microbial infections induce chemokine and cytokine cascades that coordinate
      innate immune defenses. Infection with the intracellular bacterial pathogen
      Listeria monocytogenes induces CCR2-dependent monocyte recruitment and
      activation, an essential response for host survival. Herein we show that invasive
      L. monocytogenes, but not killed or noninvasive bacteria, induce secretion of MCP
      1, the requisite chemokine for monocyte recruitment. Induction of MCP-1, but not
      TNF or IL-12, following L. monocytogenes infection is MyD88 independent.
      Consistent with these results, MyD88 deficiency does not impair monocyte
      recruitment to L. monocytogenes infected spleens, but prevents monocyte
      activation. Our results indicate that distinct microbial signals activate innate
      immune responses in an ordered, step-wise fashion, providing a mechanism to
      specify and modulate antimicrobial effector functions.

PMID- 14670306
TI  - STAT3 is required for Flt3L-dependent dendritic cell differentiation.
AB  - The signals that control decisions of progenitor commitment involve the interplay
      of both cytokines and transcription factors. Flt3L has emerged as a potential
      regulator of dendritic cell (DC) development, but regulation of HSC commitment to
      the DC lineage remains poorly understood. Our central finding is the
      identification of STAT3 activation as a checkpoint of Flt3L-regulated DC
      development. Deletion of STAT3 caused profound deficiency in the DC compartment
      and abrogated Flt3L effects on DC development. DC derivation by Flt3L revealed a
      normal HSC pool, a 2- to 3-fold accumulation of CLP/CMP, but absence of common DC
      precursors as well as their DC progeny in STAT3-deficient mice. The formation of
      CMP and CLP represents the first decisive lineage commitment step, and in this
      regard we provide evidence that commitments of CLP/CMP to the DC lineage strictly
      depend on the interplay of both Flt3L and STAT3 activation.

PMID- 14670307
TI  - WHO Working Group on the standardisation and control of pertussis vaccines-report
      of a meeting held on 6-7 May 2003, Ferney Voltaire, France.

PMID- 14670308
TI  - Herd immunity and herd protection.

PMID- 14670309
TI  - Combined hepatitis A and B vaccine in elderly.

PMID- 14670310
TI  - Immunogenicity of a combined diphtheria-tetanus-acellular pertussis vaccine in
      adults.
AB  - Two clinical studies were undertaken to evaluate the immunogenicity of an adult
      type dTpa booster vaccine (Boostrix by GlaxoSmithKline Biologicals). Blood
      samples taken prior to vaccination showed that 24.4 and 13.0% of subjects were
      seronegative for diphtheria and tetanus antibodies, respectively. Moreover, about
      one-third of the vaccinees had no detectable levels of antibodies to pertussis
      toxoid (PT) or pertactin (PRN). One month post-vaccination, more than 93% of all
      individuals, regardless of age or type of vaccine received, had seroprotective
      antibody levels for diphtheria and tetanus (> or = 0.1IU/ml). In those
      individuals vaccinated with the adult-type dTpa vaccine (Boostrix), more than 98%
      were found to be seropositive for antibodies to all three pertussis antigens (PT,
      filamentous haemogluttin (FHA), and PRN). These data suggest that immunity to
      diphtheria, tetanus and pertussis (DTP) in adults wanes and that booster
      vaccination with an adult-type combined dTpa vaccine would boost the serological
      response to diphtheria antitoxin, tetanus antitoxin and antibodies to Bordetella
      pertussis PT, FHA and PRN.

PMID- 14670311
TI  - Recombinant measles AIK-C strain expressing current wild-type hemagglutinin
      protein.
AB  - We constructed a recombinant measles virus cDNA, pIC-MVAIK-H/87-K, in which the
      hemagglutinin (H) gene of the AIK-C vaccine strain was replaced by the wild-type
      (MVi/Tokyo.JPN/87-K: genotype D3) H gene and the remaining genes were the same as
      the AIK-C vaccine strain. To investigate the feasibility of the recombinant
      vaccine strain expressing wild-type H protein instead of the AIK-C H protein, we
      constructed two recombinant measles cDNA, having Leu (small plaque-type) and Phe
      (large plaque-type) at position 278 of the F protein. Infectious chimeric virus
      strains, MVAIK-H/87-K/S (small plaque-type) and MVAIK-H/87-K/L (large plaque
      type), were recovered, which were designed to induce small (S) and large (L)
      plaques in Vero cells. The MVAIK-H/87-K/S and MVAIK-H/87-K/L did not grow at 39
      40 degrees C, similar to the original AIK-C strain, and retained the temperature
      sensitivity (ts) characteristics. They did not induce cytopathic effect (CPE) in
      Vero cells but produced CPE in B95a cells, similar to the current wild-type
      measles MVi/Tokyo.JPN/87-K. From the results of Western blotting, the mobility of
      the H protein of MVAIK-H/87-K/S and MVAIK-H/87-K/L was similar to that of
      MVi/Tokyo.JPN/87-K. Hyper-immune sera raised by MVAIK-H/87-K/S neutralized all
      types of current wild strains. Thus, the chimeric measles virus expressing the
      current wild H protein demonstrated wild-type H properties with ts
      characteristics of the vaccine strain, indicating that the construction strategy
      of recombinant measles virus can cope with the hyper-mutated measles virus.

PMID- 14670312
TI  - Attenuation of classical swine fever virus by deletion of the viral N(pro) gene.
AB  - We have reported earlier that replacement of the N(pro) gene of classical swine
      fever virus (CSFV) by the murine ubiquitin gene only slightly affects the
      characteristics of virus replication in the porcine kidney cell line SK-6 [J.
      Virol. 72 (1998) 7681]. Here, for the moderately virulent CSFV strain Alfort/187
      as well as for the highly virulent strain Eystrup we show that the respective
      N(pro)-deleted viruses are attenuated. Vaccination of pigs with either of the two
      deletion mutants resulted in the induction of a strong antibody response. Animals
      were protected against challenge with a lethal dose of highly virulent CSFV
      indicating that N(pro) deletion mutants are excellent candidates for a modified
      live virus vaccine. A chimeric virus obtained by replacement of the N(pro) gene
      in the Eystrup virus by the corresponding sequence of the avirulent CSFV vaccine
      strain Riems resulted in a virus that was highly virulent. This indicates that
      the virulence of CSFV correlates with the presence of N(pro) and also suggests
      that N(pro) is not responsible for the varying virulence observed between
      individual strains of CSFV.

PMID- 14670313
TI  - A survey of attitudes towards paediatric vaccinations amongst Canadian
      naturopathic students.
AB  - Previous studies have suggested that providers of alternative medicine may
      harbour anti-vaccination attitudes and that these attitudes may develop at an
      early stage in their careers. We further explored this question by conducting a
      survey to determine the attitudes of students of naturopathic medicine, a growing
      alternative medicine discipline, towards recommended paediatric vaccines. We
      sampled all 4 years of students at the Canadian College of Naturopathic Medicine
      (CCNM) and obtained a response rate of 59.4% (312 of 525). We found that only
      12.8% (40 of 312) of the respondents would advise full vaccination; however,
      74.4% (232 of 312) of the respondents would advise partial vaccination.
      Importantly, both willingness to advise full vaccination and trust in public
      health and conventional medicine decreased in students in the later years of the
      programme. Our findings suggest that public health and conventional medical
      supporters of vaccination need to identify mechanisms for engaging in discussion
      with this population of complementary/alternative medical professionals at an
      early stage in their careers.

PMID- 14670314
TI  - Quantification of O-acetyl, N-acetyl and phosphate groups and determination of
      the extent of O-acetylation in bacterial vaccine polysaccharides by high
      performance anion-exchange chromatography with conductivity detection (HPAEC-CD).
AB  - The O-acetyl groups in meningococcal A and typhoid Vi polysaccharides (PSs) are
      functional immunogenic epitopes in humans. To quantify and determine the extent
      of O-acetylation in these and other bacterial vaccine PSs, anion-exchange HPLC
      methods have been developed for quantification of O-acetyl, N-acetyl, and
      phosphate groups in the PSs after these groups were hydrolyzed into anions. The O
      acetylation in meningococcal A, C, Y and W-135, pneumococcal 9 V and 18C and
      typhoid Vi PSs were analyzed. The O-acetyl group was selectively released from a
      PS as acetate by mild alkaline hydrolysis in 10 or 20 mM NaOH at 37 degrees C
      until maximum release. The acetate in the hydrolysate was then quantified by high
      performance anion-exchange chromatography with conductivity detection (HPAEC-CD)
      after removal of the PS by filtration with a 10,000 molecular-weight-cut-off
      membrane. Since the extent of O-acetylation on the PSs depends on bacterial
      species, strains and growth conditions, the N-acetyl group of amino-sugars,
      phosphate or monosaccharide components of the PSs were also quantified using
      HPAEC with conductivity or amperometry detection to determine the molar ratios of
      the O-acetyl group to these components. The average numbers of O-acetyl molecules
      in one PS repeating unit of the PSs were obtained from the molar ratios. Besides
      the O-acetyl determination, the pyruvate component in non-O-acetylated
      pneumococcal type 4 PS was analyzed by the HPAEC method. The HPAEC method can
      quantify the O-acetyl content in 0.2 microg of the meningococcal C PS and has a
      sensitivity at least 10 times higher than that of the colorimetric Hestrin assay.
      The method can be used for routine analysis of O-acetylation of PSs for quality
      control of vaccine PSs.

PMID- 14670315
TI  - Comparison of immune responses and protective efficacy of suicidal DNA vaccine
      and conventional DNA vaccine encoding glycoprotein C of pseudorabies virus in
      mice.
AB  - In the present study, the immunogenicity and protective efficacy of a suicidal
      DNA vaccine (pSFVC1.5) incorporating Semliki Forest virus (SFV) replicon and
      expressing glycoprotein C (gC) of pseudorabies virus (PrV) was investigated and
      compared with a conventional plasmid DNA vaccine (pcDC) encoding the same
      antigen. In vitro, pSFVC1.5 could express gC protein and induce apoptosis of the
      transfected cells. After immunization in BALB/c mice, the gC-specific ELISA
      antibodies and neutralizing antibodies induced by pSFVC1.5 were relatively lower
      than those obtained in mice immunized with pcDC. However, mice immunized with
      pSFVC1.5 could confer more efficient protection than pcDC (100 and 62.5%,
      respectively) when challenged with the field PrV at 4 weeks after secondary
      immunization. Further analyses of cell-mediated immune responses showed that
      pSFVC1.5 induced stronger lymphocyte proliferative responses and higher levels of
      IFN-gamma, suggesting pSFVC1.5 could induce an enhanced Th1-type immune response.
      Collectively these results indicated that suicidal DNA vaccine is an alternative
      strategy to conventional DNA vaccine and can be considered a promising approach
      for the development of an efficacious vaccine against PrV.

PMID- 14670316
TI  - Effect of dose and long-term storage on the immunogenicity of murine polyomavirus
      VP1 virus-like particles.
AB  - We have analysed the stability and immunogenicity of murine polyomavirus virus
      like particles (VLPs) following intranasal administration without adjuvant. No
      morphological or immunological changes were observed in a preparation of these
      VLPs stored for 9 weeks at room temperature. Strong humoral and cellular (Th1)
      responses were obtained after a single 5.55 microg dose immunisation, which are
      efficiently boosted after a second dose. However, at dose concentrations above
      0.22 microg/microl, these VLPs appear to aggregate and, when used for
      immunisations, they fail to induce a strong cellular response, even though the
      humoral response is unaffected. These results may reflect the differential
      processing of VLP aggregates by the immune system or, alternatively, VLP
      neutralisation by antibodies induced after a primary immunisation.

PMID- 14670317
TI  - Decreased shedding of Escherichia coli O157:H7 by cattle following vaccination
      with type III secreted proteins.
AB  - Cattle are an important reservoir of Escherichia coli O157:H7 leading to
      contamination of food and water, and subsequent human disease. This pathogen
      colonizes its hosts by producing several proteins such as Tir and EspA that are
      secreted by a type III secretion system. These proteins play a role in
      colonization of the intestine, suggesting that they might be useful targets for
      the development of a vaccine to reduce levels of this organism in cattle.
      Vaccination of cattle with proteins secreted by E. coli O157:H7 significantly
      reduced the numbers of bacteria shed in feces, the numbers of animals that shed,
      and the duration of shedding in an experimental challenge model. Vaccination of
      cattle also significantly (P=0.04) reduced the prevalence of E. coli O157:H7 in a
      clinical trial conducted in a typical feedlot setting. This strategy suggests it
      is possible to vaccinate cattle to decrease the level of E. coli O157:H7 shedding
      for the purpose of reducing the risk of human disease.

PMID- 14670318
TI  - Protection of cynomolgus monkeys against HEV infection by oral administration of
      recombinant hepatitis E virus-like particles.
AB  - Hepatitis E virus (HEV) is an important causative agent of enterically
      transmitted hepatitis. Successful vaccine development is crucial in controlling
      global HEV infection. HEV capsid protein, with 111 amino acids truncated at the N
      terminus, was efficiently expressed in the baculovirus expression system.
      Expressed protein spontaneously assembled into virus-like particles (VLPs) and
      was released into culture medium. When cynomolgus monkeys were orally inoculated
      with 10mg of purified rHEV VLPs, serum IgM, IgG, and IgA responses were observed.
      All these antibody responses were obtained without adjuvants. When the monkeys
      were challenged with native HEV by intravenous injection, they were protected
      against infection or developing hepatitis. These results suggested that
      recombinant HEV (rHEV) VLPs can be a candidate for the oral hepatitis E vaccine.

PMID- 14670319
TI  - Impact of routine vaccination with a conjugate Haemophilus influenzae type b
      vaccine.
AB  - Based on a unique nationwide registration of vaccinated children, we studied the
      impact of routine Hib vaccination with special emphasis on vaccine uptake and
      adherence, vaccine effectiveness with respect to Hib meningitis, and indirect
      effects with respect to Hib meningitis among the unvaccinated children. Uptake
      and adherence was generally satisfactory. We estimated >97% effectiveness for all
      three doses of vaccine and observed herd-immunity in unvaccinated children
      comparable to a vaccine effectiveness of 94% 3.5 years into the programme. In
      conclusion, nationwide routine Hib vaccination is highly effective in protecting
      against Hib meningitis, and rapid achievement of herd immunity is possible with
      catch-up vaccination of older children.

PMID- 14670320
TI  - Binding of antibodies to human immunodeficiency virus type 1 (HIV-1)-infected
      lymphocytes elicited by vaccines and by natural infection.
AB  - Binding of antibodies to oligomeric envelope glycoprotein of R5-tropic primary
      isolates of human immunodeficiency virus type 1 (HIV-1) was studied by flow
      cytometry using sera from HIV-1 vaccine recipients and clade B and C HIV-1
      infected patients, and monoclonal and polyclonal antibodies to neutralizing
      epitopes of HIV-1. Vaccine recipients received recombinant canarypox virus
      vaccine expressing HIV-1 gene products, and SF-2 recombinant gp120 subunit
      vaccine. Anti-gp120 neutralizing antibodies including human monoclonal antibody
      2G12 and goat polyclonal anti-serum to V3 loop peptide [peptide T1-SP10MN(A)]
      bound to HIV-1-infected cells. Sera from vaccine recipients bound to HIV-1
      infected cells, but at levels lower than did infected patient sera.

PMID- 14670321
TI  - Induction of persistent in vivo resistance to Mycobacterium avium infection in
      BALB/c mice injected with interleukin-18-secreting fibroblasts.
AB  - Interferon-gamma (IFN-gamma) is closely associated with the generation of cell
      mediated immunity and resistance to intracellular parasites. Interleukin-18 (IL
      18) is known to strongly induce IFN-gamma production by T cells and natural
      killer (NK) cells. To determine whether the paracrine secretion of IL-18 can
      efficiently stimulate the resistance to Mycobacterium avium complex (MAC)
      infection, 3T3 fibroblasts were stably transfected to secrete bioactive IL-18 and
      their effects on MAC infection were investigated in genetically susceptible
      BALB/c mice, compared with that of free recombinant IL-18. Immunization with IL
      18-secreting fibroblasts (3T3/IL-18) during intranasal infection with MAC
      resulted in a significant decrease in bacterial load of lung during the entire 8
      week observation period, while rIL-18 reduced the bacterial load at initial 1
      week but not by 8 weeks postinfection. Immunization with the 3T3/IL-18 cells
      induced and maintained significantly higher levels of cytotoxic activity and
      nitric oxide production by lung cells than those of rIL-18 immunization.
      Furthermore, lung cells in mice injected with the 3T3/IL-18 cells showed
      persistent production of IFN-gamma throughout the 8-week period, suggesting that
      the 3T3/IL-18 cells induced the resistance to MAC infection via IFN-gamma
      production. This work suggests that IL-18-secreting fibroblasts may serve as a
      vehicle for paracrine secretion of IL-18 in immunotherapy of MAC infection.

PMID- 14670322
TI  - A novel antigen from Anaplasma marginale: characterization, expression and
      preliminary evaluation of the recombinant protein.
AB  - Through a process of protein fractionation and vaccination we previously
      identified four native antigens that confer a degree of protection against
      challenge with Anaplasma marginale. One of these, Ana 29 has been successfully
      cloned and sequenced using degenerate primers designed to N-terminal and internal
      peptide sequences. The full-length gene codes for a protein with a theoretical
      molecular weight of 27 kDa and pI 8.6. The sequence is highly conserved, showing
      99% identity between two Australian and an American isolate of A. marginale. The
      gene sequences from these isolates also share 99% identity with the strain of
      Anaplasma centrale used in the commercial Australian vaccine. Protein prediction
      algorithms suggest the native protein is an integral membrane protein. This
      protein has been over-expressed and purified from Escherichia coli and used in
      vaccination trials in cattle using two adjuvants. The initial results from the
      trial show a significant level of protection was obtained with one adjuvant; in
      comparison, the second adjuvant slightly aggravated the disease. Preliminary data
      suggests a good correlation between the induction of an IgG2 response and
      protection.

PMID- 14670323
TI  - Suppressive effect of zinc on antibody response to cholera toxin in children
      given the killed, B subunit-whole cell, oral cholera vaccine.
AB  - In a previous study, children aged 2-5 years old in Bangladesh were supplemented
      orally with a single dose of Vitamin A (200,000 IU) and a placebo for zinc (zinc
      equivalent to 20 mg of elemental zinc) everyday for 42 days (group A), zinc and a
      placebo for Vitamin A (group Z), zinc and Vitamin A (group AZ) or both placebos
      (group P). All children were orally immunised with two doses of the killed
      cholera vaccine containing whole cells and a recombinant B subunit of cholera
      toxin (CT). The number of children who responded with > or = 4-fold vibriocidal
      antibody (a proxy indicator of protection against cholera) was significantly
      greater among the zinc-supplemented groups than among the non-zinc-supplemented
      groups, while Vitamin A supplementation did not appear to have any effect. The
      sera from these children were assayed for antibody to CT. Antibody to CT is known
      to exert a synergistic protective effect against cholera in animal studies, and
      offer significantly higher short-term protection against cholera and significant
      short-term protection against enterotoxigenic Escherichia coli diarrhoea in
      humans on oral immunisation with the cholera vaccine. Children who received zinc
      had significantly reduced levels of serum antibodies to CT than children who
      received placebos only. Factorial analysis showed a trend for zinc showing a
      reduction in the number of children responding with CT-antibody, while Vitamin A
      did not appear to have any effect. Thus, zinc enhanced vibriocidal antibody
      response, but suppressed CT-antibody response, suggesting that zinc
      supplementation has different modulating effects on vibriocidal antibody response
      and CT-antibody response.

PMID- 14670324
TI  - Defining a serological correlate of protection in rabbits for a recombinant
      anthrax vaccine.
AB  - In these studies, a serological correlate of protection against anthrax was
      identified in New Zealand white (NZW) rabbits that had been given one or two
      injections of various amounts of recombinant protective antigen (rPA) combined
      with aluminum hydroxide adjuvant (Alhydrogel). Rabbits were subsequently
      challenged by the aerosol route with spores of the Ames isolate of Bacillus
      anthracis. Results suggested that the antibody response, as determined by the
      quantitative anti-rPA IgG ELISA and toxin neutralizing antibody (TNA) assay, were
      significant predictors (P<0.0015) of protection against a B. anthracis aerosol
      spore challenge in rabbits.

PMID- 14670325
TI  - Co-immunization with an HIV-1 Tat transduction peptide-rotavirus enterotoxin
      fusion protein stimulates a Th1 mucosal immune response in mice.
AB  - The cholera toxin B subunit (CTB) and a 12 aa HIV-1 Tat transduction peptide were
      genetically linked to a 90 aa peptide from the murine rotavirus non-structural
      enterotoxin protein (NSP4) for comparison of receptor directed and transduction
      peptide mediated antigen targeting to the gut associated lymphoid tissues for
      enhanced protection against rotavirus infection. Oral immunization with Tat
      NSP4(90) fusion protein isolated from Escherichia coli generated detectable anti
      NSP4(90) IgG titers in mice. CTB-NSP4(90) fusion protein stimulated higher serum
      IgG titers than CTB fused to a 22 aa immunodominant epitope NSP4(22) indicating
      the presence of additional immunogenic epitopes in the NSP4(90) peptide. Mice
      immunized with CTB-NSP4(22) stimulated high IgG2a antibody levels suggesting a
      dominant Th1 lymphocyte response. However, mice immunized with CTB-NSP4(90)
      generated similar levels of IgG1 and IgG2a suggesting equal stimulation of Th1
      and Th2 responses. Mice co-immunized with CTB-NSP4(90) and Tat-NSP4(90) fusion
      proteins generated dominant IgG2a levels indicating that the two ligands co
      operate to generate an increased Th1 response.

PMID- 14670326
TI  - Recombinant hepatitis B core antigen carrying preS1 epitopes induce immune
      response against chronic HBV infection.
AB  - Many studies have provided evidence that core antigen of hepatitis B virus
      (HBcAg) is extremely immunogenic, HBcAg can be function as both a T-cell
      dependent antigen and a T-cell-independent antigen, and thus may be a promising
      candidate for therapeutic vaccine for control of chronic HBV infection. HBcAg is
      also an effective carrier for heterologous peptide epitopes. The preS1 is a
      surface protein of HBV and is immunogenic at the T and B cell level. The amino
      acid sequence 21-47 of preS1 is crucial for HBV binding to human hepatocytes as
      well as to PBMC and haematopoietic cell lines of the B cell lineage. Here we
      expressed a chimeric protein named HBVCS1, created by fusing the preS1 sequence 3
      55 to the carboxyl terminus of the truncated HBcAg sequence 1-155 in E. coli.
      Analysis of its antigenicity and immunogenicity revealed that both HBc and preS1
      epitopes are surface accessible, and that fusion of preS1 did not affect the HBc
      antigenicity and immunogenicity of the truncated HBc sequence. HBVCS1 induced
      strong anti-HBc and moderate anti-preS1 immune responses as well specific T-cell
      response in Balb/c mice. HBVCS1 vaccination reduced of the titer of HBsAg and HBV
      DNA in sera of HBV-Tg mice. These results indicate that HBVCS1 may have potential
      as a therapeutic vaccine for treatment of HBV chronic infection.

PMID- 14670327
TI  - DNA immunisation: altering the cellular localisation of expressed protein and the
      immunisation route allows manipulation of the immune response.
AB  - DNA immunisation by intramuscular (IM) injection induces Th1 responses, whereas
      gene gun (GG) immunisation into the skin stimulates Th2 responses. Three
      ovalbumin (OVA) cDNA constructs, in which OVA is cytoplasmic (CYT), secreted
      (SECR), or transmembrane (TM), were compared in immunisation studies using
      intramuscular injection or biolistic bombardment of the skin. Gene gun
      immunisation with OVA-CYT or OVA-TM led to strong OVA-specific CTL responses, but
      not following OVA-SECR immunisation. In contrast, intramuscular immunisation with
      OVA-SECR or OVA-TM led to potent CTL while immunisation with OVA-CYT was
      ineffective. OVA-specific antibodies were detected following gene gun
      immunisation with all three constructs, whereas only the OVA-SECR construct
      induced antibody production following intramuscular immunisation. These results
      demonstrate the capacity to manipulate the nature of the immune response by
      altering the cellular localization of expressed proteins and the route of DNA
      immunisation.

PMID- 14670328
TI  - Immunization of woodchucks with adjuvanted sHDAg (p24): immune response and
      outcome following challenge.
AB  - The immunogenicity and the protection induced by an hepatitis delta virus (HDV)
      vaccine consisting of the small nucleoprotein (HDAg) (p24) and adjuvanted with
      MF59 or Freund's adjuvant (FA) were evaluated in woodchucks chronically infected
      with woodchuck hepatitis virus (WHV) and challenged with hepatitis delta virus.
      Humoral and T-cell-mediated responses to HDAg were measured. Anti-HD antibodies
      appeared earlier in the FA/p24 animals. After challenge, all MF59/p24 vaccinated
      animals showed a response to HDAg-derived peptides, compared to two of the five
      FA/p24 animals and one of the control animals. Serum HDV-RNA peak values and
      persistence were considerably reduced in immunized animals, in comparison to
      controls. Furthermore, HDV-RNA was absent in autopsy liver tissues of 50% of the
      MF59/p24 animals, whereas high levels were present in all of the FA/p24 animals
      and controls. Histological liver analysis performed before and after challenge
      revealed the presence of acute hepatitis-like lesions only in the controls.
      Overall, the results suggest that the MF59/p24 vaccine better controls the
      infection in terms of viral replication and survival.

PMID- 14670329
TI  - Immune response of pigs inoculated with Mycobacterium bovis BCG expressing a
      truncated form of GP5 and M protein of porcine reproductive and respiratory
      syndrome virus.
AB  - Pigs were immunised with recombinant BCG (rBCG) expressing a truncated form of
      GP5 (lacking the first 30 NH(2)-terminal residues) (rBCGGP5) and M protein
      (rBCGM) of porcine reproductive and respiratory syndrome virus (PRRSV). At 30
      days post-inoculation (dpi), pigs inoculated with rBCGGP5 and rBCGM developed a
      specific humoral immune response against the viral proteins, as detected by
      commercial ELISA and Western blot tests, and at 60 dpi, three out of five animals
      developed neutralizing antibodies with titers ranging from 1:4 to 1:8. At 67 dpi,
      an IFN-gamma response against BCG antigens, but not against the viral proteins,
      was detected by ELISPOT in inoculated pigs. Following challenge with a pathogenic
      strain of PRRSV, pigs inoculated with rBCG showed lower (P<0.05) temperature,
      viremia and virus load in bronchial lymph nodes than control animals, suggesting
      the establishment of partial protection against PRRSV infection.

PMID- 14670330
TI  - Cost-effectiveness of three different vaccination strategies against measles in
      Zambian children.
AB  - The vaccination program in Zambia includes one dose of measles vaccine at 9
      months of age. The objective of this study was to compare the cost-effectiveness
      of the current one-dose measles vaccination program with an immunization schedule
      in which a second dose is provided either through routine health services or
      through supplemental immunization activities (SIAs). We simulated the expected
      cost and impact of the vaccination strategies for an annual cohort of 400,000
      children, assuming 80% vaccination coverage in both routine and SIAs and an
      analytic horizon of 15 years. A vaccination program which includes SIAs reaching
      children not previously vaccinated would prevent on additional 29,242 measles
      cases and 1462 deaths for each vaccinated birth cohort when compared with a one
      dose program. Given the parameters established for this analysis, such a program
      would be cost-saving and the most cost-effective vaccination strategy for Zambia.

PMID- 14670331
TI  - Protective immunity induced in mice by F0 and FII antigens purified from
      Paracoccidioides brasiliensis.
AB  - Paracoccidioides brasiliensis causes a chronic granulomatous mycosis prevalent in
      South America, and cell-mediated immunity represents the principal mode of
      protection against this fungal infection. We investigated whether immunization
      with P. brasiliensis antigens fractionated by anionic chromatography on fast
      protein liquid chromatography (FPLC) could elicit protective immunity. BALB/c
      mice were immunized by subcutaneous injection of either 10 microg fractions 0
      (F0), II (FII) or III (FIII) in the presence of 100 microg of Corynebacterium
      parvum and 1 mg of Al(OH)(3) and challenged with pathogenic P. brasiliensis
      strain. Mice immunized with F0 presented cellular and humoral immune responses
      with significant production of IFN-gamma, and high levels of IgG2a and IgG3
      isotypes. Immunization with FII induced significant production of IFN-gamma and
      IL-10 associated with high levels of IgG1 and IgG2a. It was demonstrated that
      immunization with F0 or FII promoted significant decrease of organ colony-forming
      units (CFUs) in the lung after challenge infection without fungi dissemination to
      the spleen or liver. In contrast, FIII immunized mice develop a progressive
      disseminated disease to spleen and liver presented significant levels of INF
      gamma, IL-10 or TGF-beta associated with high production of IgG1 and IgG2a with
      low production of IgG2b and IgG3 after challenge infection. Taken together, these
      findings suggest that antigens of F0 and FII are reliable vaccine candidates
      against the paracoccidioidomycosis.

PMID- 14670332
TI  - Maternal antibodies block induction of oral tolerance in newly hatched chicks.
AB  - Oral antigens administered to newly hatched chicks induce oral tolerance. Some of
      the antigens encountered via the gut during this period are pathogen-derived, and
      should not be tolerogenic. As chicks are protected in early life by maternal
      antibodies, we assumed that the same antibodies also served to prevent tolerance
      by blocking the relevant antigen. We used bovine serum albumin (BSA) as a model
      antigen, and initially showed that tolerance was invariably generated in chicks
      younger than 3 days of age. We then showed that tolerance and its prevention were
      due to circulatory BSA: intravenous BSA induced tolerance, BSA was present in
      serum of previously fed chicks, and tolerance was completely blocked in chicks
      containing high levels of maternal anti-BSA. These findings indicate that
      tolerance in the young chick is probably generated in central lymphoid organs,
      and that maternal antibodies block access of antigen to these organs, thereby
      preserving immune competence.

PMID- 14670333
TI  - IL-12 enhances protective immunity in mice engendered by immunization with
      recombinant 14 kDa Schistosoma mansoni fatty acid-binding protein through an IFN
      gamma and TNF-alpha dependent pathway.
AB  - Herein, we tested the ability of IL-12 to enhance protection induced by
      recombinant Sm14 (rSm14). Mice immunization with three doses of 25 microg of
      rSm14 was able to induce 25% of protection in mice against challenge. However, co
      administration of exogenous IL-12 enhanced protective immunity engendered by
      rSm14 from 25 to 42.2%. Higher levels of IgG2a and TNF-alpha were observed in
      mice immunized with rSm14 plus IL-12 compared to animals vaccinated with rSm14
      alone. Regarding other cytokines, significant amounts of IFN-gamma were measured
      in splenocyte culture supernatants of rSm14/IL-12 or rSm14 vaccinated mice and no
      IL-4 was detected. In an attempt to determine the role of IFN-gamma and TNF-alpha
      in IL-12 induced immunity, IFN-gamma and TNFR-p55 knockout mice were immunized
      with rSm14/IL-12 and no protection was achieved. Therefore, protection induced by
      rSm14/IL-12 was shown to be dependent on endogenous IFN-gamma and TNF-alpha.
      Although, rSm14 immunization induced partial protection, reduction of hepatic
      granuloma area was only observed when IL-12 was co-administered.

PMID- 14670334
TI  - Hepatitis B immunisation induces higher antibody and memory Th2 responses in new
      borns than in adults.
AB  - New-borns raise limited antibody responses to most T cell-dependent antigens but
      little is known about neonatal T lymphocyte responses to vaccines. In this study,
      we compared the immune response induced by the hepatitis B vaccine in new-borns
      and nai;ve adults. Infants produced markedly higher serum anti-hepatitis B
      surface (HBs) antibody titres than adults. This was not associated with greater
      HBs Ag-specific Th2 cytokine responses but with lower primary IFN-gamma
      responses. At 1 year, the infant memory response to HBs Ag was characterised by
      higher Th2 responses than those of adults. We conclude that neonatal antibody and
      T cell responses to hepatitis B vaccine differ from those induced in adults.

PMID- 14670335
TI  - Antitumor efficacy of Venezuelan equine encephalitis virus replicon particles
      encoding mutated HPV16 E6 and E7 genes.
AB  - An effective vaccine for treating human papillomavirus (HPV)-associated
      malignancies such as cervical cancer should elicit strong T cell-mediated
      immunity (CMI) against the E6 and/or E7 proteins necessary for the malignant
      state. We have developed Venezuelan equine encephalitis (VEE) virus replicon
      particle (VRP) vaccines encoding the HPV16 E6 and E7 genes and tested their
      immunogenicity and antitumor efficacy. The E6 and E7 genes were fused to create
      one open reading frame and mutated at four or at five amino acid positions to
      inactivate their oncogenic potential. VRP encoding mutant or wild type E6 and E7
      proteins elicited comparable cytotoxic T lymphocyte (CTL) responses to an
      immunodominant E7(49-57) epitope and generated comparable antitumor responses in
      several HPV16 E6(+)E7(+) tumor challenge models: protection from either C3 or TC
      1 tumor challenge was observed in 100% of VRP-vaccinated mice. Eradication of C3
      tumors was observed in approximately 90% of mice following therapeutic VRP
      vaccination. Eradication of HLF16 tumors lacking the E7(49-57) epitope was
      observed in 90% of human leukocyte antigen (HLA)-A(*)0201 transgenic mice
      following therapeutic VRP vaccination. Finally, the predicted inactivation of E6
      and E7 oncogenic potential was confirmed by demonstrating normal levels of both
      p53 and retinoblastoma proteins in human mammary epithelial cells (MEC) infected
      with VRP expressing mutant E6 and E7 genes. These promising results support the
      continued development of mutant E6 and E7 VRP as safe and effective candidates
      for clinical evaluation against HPV-associated disease.

PMID- 14670336
TI  - The functional consequences of delivery of HIV-1 Nef to dendritic cells using an
      adenoviral vector.
AB  - The Nef gene is a major determinant of HIV-1 pathogenicity. Several
      immunomodulatory functions have been reported for Nef, including down-regulation
      of CD4 and class I MHC in T-lymphocytes, and the ability to enhance viral
      transmission from macrophages and dendritic cells (DC) to T-lymphocytes. In this
      study, HIV-1 (SF2 strain) Nef was expressed in human monocyte-derived dendritic
      cells, using an adenovirus based delivery system. Nef expression resulted in
      decreased CD4 levels, but no change to class I MHC, and no impairment in the
      ability of DC to stimulate recall PPD responses, mixed leukocyte responses, or
      hepatitis B-specific CD8 responses. The adenovirus vector itself stimulated a
      strong recall CD4 response in all individuals tested, and also induced up
      regulation of class I MHC, CD86 and CD40 on the dendritic cell surface. The study
      provides no evidence that HIV Nef impairs the function of human dendritic cells,
      and suggests that delivery of Nef to dendritic cells may be one strategy with
      which to stimulate an HIV-1 immune response.

PMID- 14670337
TI  - Post-marketing evaluation of the short term safety of COMVAX.
AB  - We report an evaluation of the short-term safety of a pediatric bivalent
      combination vaccine containing RECOMBIVAXHB and Liquid PedvaxHIB, COMVAX. Safety
      was assessed through identification of medical utilization; potential adverse
      events were identified through computerized clinical databases for deaths,
      hospitalizations, emergency room visits, and outpatient clinic visits. We
      calculated relative risks whenever there was at least one diagnosis-specific
      event in the risk period following vaccination and compared the rates in specific
      time windows following vaccination with rates at 31-60 days following vaccination
      and also with rates in a historical cohort of children. A total of 27,802 doses
      of COMVAX were administered, with 127 separate adverse event codes with
      statistically significant elevated risks, and 66 codes with significantly
      decreased risks. Most potentially serious diagnoses appeared in four major
      categories: "Respiratory Events"; "Gastroenteritis"; "Adverse Effect of Medicinal
      and Biological Substance, NOS"; and "Fever". There was no consistent pattern to
      indicate increased risks for serious respiratory or gastrointestinal illness. For
      fever, most of the findings appeared to be explained by changes in data
      collection or by concomitant vaccination with M-M-R(-)II. There was an increased
      risk for fever hospitalizations following shot 1. The total number of children
      hospitalized with fever was seven out of 12,468 children; all recovered fully. In
      this study population of 27,802 vaccine recipients, COMVAX appeared to have a
      favorable safety profile.

PMID- 14670339
TI  - Tuberculosis and leprosy: potential novel drugs and vaccines against
      Mycobacterium. A Symposium held at Universiti Malaysia Sabah, Kota Kinabalu,
      Sabah, Malaysia, July 3-5, 2002. Proceedings.

PMID- 14670340
TI  - Tuberculosis in Malaysia: problems and prospect of treatment and control.
AB  - In the early 1940s and 1950s, tuberculosis (TB) was the number one cause of death
      in Malaysia. Patients with TB were admitted to the many sanatoria we had in
      various parts of the country and were often managed by surgical means. TB
      chemotherapy became available only in the late 1950s. At this time, TB was
      already a major cause of morbidity and mortality. Realizing its seriousness, the
      Malaysian government launched its National TB Control Programme (NTP) in 1961. At
      that time, the recommended treatment for TB was a combination of three drugs,
      namely, streptomycin, isoniazid and paraaminosalicylic acid (PAS) given for 2
      months followed by isoniazid and PAS given for 12 months. Generally the treatment
      used to last for 1-2 years. The National TB Centre in Kuala Lumpur functioned as
      the headquarters of the NTP, and the state general hospitals with their chest
      clinics functioned as the state directorates. From the operational point of view,
      every state has a state TB directorate which is known as the State TB Managerial
      Team (Fig. 1). This team is responsible for the implementation of the activities
      of the NTP at the state and district levels. Ever since 1995, the national TB
      directorate has been shifted to the Public Health Division of the Ministry of
      Health (MOH) and is now under the Director of Disease Control (Fig. 2). The
      National TB Centre has now been renamed as The Institute of Respiratory Medicine.
      Over the years from being the number one cause of death, TB has dropped to being
      below number 10 (Fig. 3).

PMID- 14670341
TI  - Epidemiology of tuberculosis and leprosy, Sabah, Malaysia.
AB  - The objectives in this epidemiology review are to measure and report the extent
      of morbidity and mortality due to tuberculosis (TB), the proportion of new sputum
      smear positive cases in districts and the status of cohort analysis as of 1999.
      As for leprosy, the main objective is to determine morbidity and the treatment
      outcomes of Multiple Drug Therapy (MDT). Based on the results obtained, a
      comprehensive action plan for prevention, control and monitoring of tuberculosis
      and leprosy cases and patients is being produced and implemented throughout the
      state. The analysis concentrated on patients diagnosed at all out-patient units
      and admitted in all of the state's hospitals. The patient particulars were
      recorded using a standardized format based on TB and Leprosy Health Management
      Information System (TB HMIS). TB was the second highest by notification of
      communicable diseases in Malaysia in 2001. 29% or about one-third of the national
      TB cases are from Sabah. However, it has been noted that there was an average
      decline of 2.6% in annual notification since 10 years ago to date. There was also
      a reduction of 11.4% in 2001 as compared to annual notification in 2000.
      Immigrants contribute more than 24% in detection of new cases since 1990.
      Treatment success rate in term of completion of treatment to date is 82%.
      Mortality rate has steadily declined from 14 deaths to 7 deaths per 100,000
      population. Leprosy in Sabah also contributes to 30% of the yearly total caseload
      of Malaysia and has the highest notification rate of 2 per every 100,000
      population as compared to other states. The average registered leprosy cases over
      the past 5 years are 239 cases and the prevalence rate is 0.7/10,000 population.
      The state has successfully achieved its goal to decrease leprosy as per the World
      Health Organization (WHO) goal of yearly overall prevalence rate of less than 1
      case for every 10,000 population. However, the districts of Kudat, Tawau, Lahad
      Datu, Kota Kinabalu and Semporna are still within the prevalence rate of more
      than one per 10,000 population. This review highlights some interesting findings
      which can be incorporated into the State and Districts action plans and
      strategies. It is also noted that in order to translate National Plans and
      Strategies into effective action at the community level, health workers need
      relevant up-to-date knowledge of the pattern of health and disease, and of their
      determinants, in each district. The Sabah Health Department continues to organize
      and support programs related to management and control of tuberculosis and
      leprosy to progressively reduce the incidence of these diseases in the community
      by breaking the chain of transmission of Mycobacterium tuberculosis and M.
      leprae, respectively.

PMID- 14670342
TI  - Risk factors of tuberculosis among health care workers in Sabah, Malaysia.
AB  - Tuberculosis (TB) is one of the main public health problems in Sabah; 30% of the
      total number of TB cases reported in Malaysia every year occur in Sabah. The
      average incidence of TB among health care workers over the past 5 years is 280.4
      per 100,000 population (1, Annual Report of Sabah State TB Control Programme,
      1998). At present, there are no specific measures for the prevention of TB
      transmission in health care facilities. A case-control study was conducted among
      health care workers in Sabah in 2000-2001. Cases were health care workers with TB
      diagnosed between January 1990 and June 2000. Controls were health care workers
      without TB and working in the same facility as cases during the disease episode.
      The study attempted to identify risk factors for TB among the study population.
      Data were collected through structured interviews and review of patients'
      records. The notification rate of TB among health care workers was significantly
      higher than that to the general population (Z=4.893, p<0.01). The average
      notification rate of TB among health care workers over the last 5 years was two
      times higher than in the general population (280.4/100,000 compared to
      153.9/100,000). Regression results showed that ethnicity, designation, family
      contact and TB related knowledge did not significantly contribute to the risk of
      contracting TB in this study. However, after controlling for the above factors,
      age, gender, history of TB contact outside the workplace (other than family
      contact), duration of service and failure to use respiratory protection when
      performing high-risk procedures, were the main risk factors of TB among health
      care workers. This study succeeded in identifying some of the risk factors of TB
      among health care workers. We managed to include the large ratio of controls to
      case (3:1) and those cases spanned over a period of 10 years. However, the
      findings from the study have to be applied with caution due to the limitations of
      this study, which include recall bias, dropouts, and small sample size. Based on
      the study findings, we recommend that health care workers in the first 10 years
      of service should take extra precautions, such as using respiratory protection
      when performing procedures that are considered to be of high risk with respect to
      TB infection. They should also undergo TB screening at least once every 2 years
      and, if symptomatic, offered prophylactic treatment. The Respiratory Protection
      Programme should be fully implemented to help reduce the risk of TB among health
      care workers in Sabah.

PMID- 14670343
TI  - Tuberculosis of the spine-the Sabah experience. Epidemiology, treatment and
      results.
AB  - A retrospective review of 33 patients with tuberculosis of the spine from January
      2000 to April 2002 revealed that the mean age was 36.5 and peak incidence is in
      the second decade of life (27.3%). There were 24 males and 9 females. The
      majority of the lesions involved the thoracic spine (30.3%), followed by the
      lumbar spine (27.2%). Skip lesions was seen in 12.1% of cases. The erythrocyte
      sedimentation rate was normal in 9.1% of patients. Neurological involvement was
      seen in 51.5% of patients. Concomitant tuberculosis of the lung was 66.6%. The
      radical surgical debridement and grafting rate was 39.3%. The preferred surgical
      procedure was that of radical anterior debridement and fusion supplemented by
      anterior or posterior instrumentation if needed. Anti-tuberculous chemotherapy
      remained the mainstay of treatment. Surgery gives faster relief of pain and
      neurological recovery but is a major undertaking, and thus selection of patients
      is vital to avoid morbidity and mortality.

PMID- 14670344
TI  - M. tuberculosis persistence, latency, and drug tolerance.
AB  - The success of Mycobacterium tuberculosis as a pathogen is largely attributable
      to its ability to persist in host tissues, where drugs that are rapidly
      bactericidal in vitro require prolonged administration to achieve comparable
      effects. Latency is a frequent outcome of untreated or incompletely treated M.
      tuberculosis infection, creating a long-standing reservoir of future disease and
      contagion. Although the interactions between the bacterium and its host that
      result in chronic or latent infection are still largely undefined, recent years
      have seen a resurgence of interest and research activity in this area. Here we
      review some of the classic studies that have led to our current understanding of
      M. tuberculosis persistence, and discuss the varied approaches that are now being
      brought to bear on this important problem.

PMID- 14670345
TI  - TB drug discovery: addressing issues of persistence and resistance.
AB  - Tuberculosis remains a leading cause of mortality worldwide into the 21st
      century. Among the main obstacles to the global control of the disease are
      emerging multi-drug resistant strains and the recalcitrance of persistent
      infections to treatment with conventional anti-TB drugs. Here we review recent
      developments in our understanding of some of the pathways involved in a
      persistent infection and pathogenesis of Mycobacterium tuberculosis, which reveal
      new targets for drug development. We describe the high-resolution crystal
      structures of enzymes of the glyoxylate shunt, isocitrate lyase and malate
      synthase, and of the cyclopropane synthases of mycolic acid biosynthesis.
      Structure-based drug design is now underway with the potential to lead to the
      development of new anti-tuberculars effective against persistent and resistant
      Mycobacterium tuberculosis infections.

PMID- 14670346
TI  - Susceptibility of Mycobacterium tuberculosis to isoniazid and its derivative, 1
      isonicotinyl-2-nonanoyl hydrazine: investigation at cellular level.
AB  - In this study, the susceptibility of Mycobacterium tuberculosis to isoniazid
      (INH) was compared with its derivative, 1-isonicotinyl-2-nonanoyl hydrazine (INH
      C9), prepared synthetically. The minimum inhibitory concentration (MIC) of the
      drugs was determined using the 1% proportion method. INH-C9 was found to lower
      the MIC of INH from 0.05 to 0.025 microg/ml. Further studies on the effects of
      INH and INH-C9 on M. tuberculosis were assessed by exposing the cells to the
      above at the MIC level. M. tuberculosis cells grown on Middlebrook 7H10 agar were
      harvested at different stages of their growth cycle (initial stage, 24 and 72 h),
      exposed to the MICs of INH and INH-C9, and stained with acid-fast staining. The
      observations were made for a week. The cellular morphologies and staining
      characteristics were examined using a Brightfield microscope. The result
      indicated cells only at the initial stage of growth were most susceptible to the
      drugs resulting in the loss of acid-fastness and intact cellular morphology in
      the majority of cells.

PMID- 14670347
TI  - Molecular genetics of Mycobacterium tuberculosis in relation to the discovery of
      novel drugs and vaccines.
AB  - Genetic systems that allow mycobacterial genomes to be mutagenized in a targeted
      or random fashion have provided the means for developing new tools for the
      diagnosis, prevention and treatment of tuberculosis by allowing potential targets
      to be identified and validated. In this review, we highlight key historical
      developments in the field of mycobacterial genetics, which have yielded the
      powerful repertoire of genetic tools that are now in hand and provide examples
      that illustrate their use in exploring specific aspects of mycobacterial
      metabolism.

PMID- 14670348
TI  - Genetic susceptibility to pulmonary tuberculosis in Cambodia.
AB  - We have studied the risk of progression to active pulmonary tuberculosis (TB)
      among a population of Cambodian rural poor suffering from one of the highest
      global incidences of TB. Together with a community-based TB program, we have
      established a research partnership that has demonstrated the association of a
      particular HLA binding motif and progression to active pulmonary TB. We have also
      shown that candidate gene polymorphisms are ethnic specific and unique in
      Cambodia and are likely markers for as yet unidentified disease susceptibility
      and resistance loci. We have also uncovered a high incidence of antigen-specific
      anergy to purified protein derivative among patients with active pulmonary TB and
      have correlated this with an expansion of immunosuppressive IL-10 producing T
      cells and other impaired T cell responses to mycobacterial antigens. These
      experiments lend insight into TB susceptibility and the molecular mechanisms of
      antigen-specific anergy. Moreover, they demonstrate that a partnership between TB
      cure and scientific discovery is possible in even the most impoverished settings.

PMID- 14670349
TI  - Molecular mechanisms of MHC linked susceptibility in leprosy: towards the
      development of synthetic vaccines.
AB  - Tuberculoid (TT) and lepromatous leprosy (LL) develop in the human host depending
      on his ability to trigger a specific cellular immune response(CIR). Different
      genes have been demonstrated in susceptibility/protection and may explain the
      forms of leprosy. The major histocompatibility complex (MHC) play an important
      role. The aim of the study was to explore the contribution of human leukocyte
      antigen (HLA) DRB1, DQA1, DQB1 and DQ promoter genes in LL Mexican patients. Six
      families (26 LL, three TT patients and 27 controls) were analyzed; 114 unrelated
      patients were compared with 204 controls. Class I typing was done by the standard
      microlymphocytotoxicity and class II typing using PCR-SSOP. Haplotype segregation
      correlated with specific CIR in vivo and in vitro using lepromin. Haplotype
      sharing was significantly deviated in the affected sibs (p=0.01). Six healthy
      sibs were non-responders to lepromin and four of them were DQ1 homozgotes. DQ1
      was significantly associated with LL and with non-responders. We set up
      macrophage activation experiments after infecting these cells with 5x10(6)
      bacilli to demonstrate if elimination occurred in the context or DQ1. When DQ1
      was present on macrophages and on T cells, bacteria were poorly eliminated from
      the cell (32%) while when absent, 76% of the individuals were able to eliminate
      the bacilli (p=0.03). DRB1*1501 DQA1*0102-DQB1*0602 (DQ1 subtype) was
      significantly increased in the patients, indicating its participation in
      susceptibility. QBP 5.11/5.12 promoter present in the mentioned haplotype, and
      QAP 1.4, linked to DRB1*1301/02 haplotypes were also associated. Two mechanisms
      are suggested: the promoter polymorphisms may influence allele expression and
      thus the amount of peptides presented to the T-cell receptor, leading to a
      deficient CIR: HLA restriction is important for vaccine design; the way peptides
      anchor the DRB1*1501 groove may be relevant to the activation of TH1 cells, which
      contribute to an efficient presentation of peptides inducing a protective T-cell
      response.

PMID- 14670350
TI  - Immunology of tuberculosis and implications in vaccine development.
AB  - Mycobacterium tuberculosis is a very successful pathogen that can survive and
      persist in the human host in the face of a robust immune response. This immune
      response is sufficient to prevent disease in the majority of infected persons,
      providing compelling evidence that immunity to tuberculosis is possible. However,
      it is more striking that the strong immune response is not generally effective at
      eliminating the organisms, during either initial infection or the persistent or
      latent phase of infection. Studies in animal models and in humans have
      demonstrated the wide range of immune components involved in the effective
      response against M. tuberculosis. These components include T cells (both CD4+ and
      CD8+), cytokines, including IFN-gamma, IL-12, TNF-alpha, and IL-6, and
      macrophages. The precise roles and functions of these cells and molecules (and
      others) are still being defined and may differ in acute and chronic infection.
      These immune responses are directed towards containing or eliminating the
      tubercle bacillus within the tissues of the host. The estimated eight million new
      cases of tuberculosis each year clearly demonstrate that these responses are not
      always effective. M. tuberculosis has obviously evolved a variety of mechanisms
      to evade destruction by the immune response. Studying both the host and the
      pathogen will elucidate potential vaccine candidates. In this review, the known
      functions of immune components in the response to M. tuberculosis and
      implications for vaccine development will be discussed.

PMID- 14670351
TI  - Approaches towards the development of a vaccine against tuberculosis: recombinant
      BCG and DNA vaccine.
AB  - The last few years have witnessed intense research on vaccine development against
      tuberculosis. This has been driven by the upsurge of tuberculosis cases globally,
      especially those caused by multi-drug-resistant Mycobacterium tuberculosis
      strains. Various vaccine strategies are currently being developed which can be
      broadly divided into the so-called living and non-living vaccines. Examples are
      attenuated members of the M. tuberculosis complex, recombinant mycobacteria,
      subunit proteins and DNA vaccines. Given current developments, we anticipate that
      recombinant BCG and DNA vaccines are the most promising. Multiple epitopes of M.
      tuberculosis may need to be cloned in a vaccine construct for the desired
      efficacy to be achieved. The technique of assembly polymerase chain reaction
      could facilitate such a cloning procedure.

PMID- 14670352
TI  - Iron, mycobacteria and tuberculosis.
AB  - The role of iron in the growth and metabolism of M. tuberculosis and other
      mycobacteria is discussed in relation to the acquisiton of iron from host
      sources, such as transferrin, lactoferrin and ferritin, and its subsequent
      assimilation and utilization by the bacteria. Key components involved in the
      acquisition of iron (as ferric ion) and its initial transport into the
      mycobacterial cell are extracellular iron binding agents (siderophores) which, in
      pathogenic mycobacteria, are the carboxymycobactins and, in saprophytic
      mycobacteria, are the exochelins. In both cases, iron may be transferred to an
      intra-envelope, short-term storage molecule, mycobactin. For transport across the
      cell membrane, a reductase is used which converts FeIII-mycobactin to the FeII
      form. The ferrous ion, possibly complexed with salicylic acid, is then shuttled
      across the membrane either for direct incorporation into various porphyrins and
      apoproteins or, for storage of iron within the bacterial cytoplasm,
      bacterioferritin. The overall process of iron acquisition and its utilization is
      under very genetic tight control. The importance of iron in the virulence of
      mycobacteria is discussed in relationship to the development of tuberculosis. The
      management of dietary iron can therefore be influential in aiding the outcome of
      this disease. The role of the old anti-TB compound, p-aminosalicylate (PAS), is
      discussed in its action as an inhibitor of iron assimilation, together with the
      prospects of being able to synthesize further selective inhibitors of iron
      metabolism that may be useful as future chemotherapeutic agents.

PMID- 14670353
TI  - Learning and adult neurogenesis: survival with or without proliferation?
AB  - Recent high quality papers have renewed interest in the phenomenon of
      neurogenesis within the adult mammalian brain. Many studies now show that
      neurogenesis can be modulated by environmental factors including physical
      activity, stress, and learning. These findings have considerable implications for
      neuroscience in general, including the study of learning and memory, neural
      network plasticity, aging, neurodegeneration, and the recovery from brain injury.
      Although new light has been shed on this field, many contradictory findings have
      been reported. Here we propose two principle issues which underlie these
      inconsistencies, with particular focus on the interaction between learning and
      neurogenesis. The first issue relates to the basic methodology of measuring the
      generation of new brain cells, i.e., proliferation, as compared to survival of
      the newly made cells. Mostly, measures of neurogenesis reported are a combination
      of proliferation and survival, making it impossible to distinguish between these
      separate processes. The second aspect is in regards to the role of environmental
      factors which can affect both proliferation and survival independently.
      Especially the interaction between stress and learning is of importance since
      these might counteract each other in some circumstances. Reviewing the literature
      while taking these issues into account indicates that, in contrast to some
      findings, cell proliferation in the dentate gyrus of the hippocampus as a result
      of learning cannot be ruled out yet. On the other hand, increased survival of
      granule cells in the dentate gyrus as a result of hippocampal-dependent learning
      has been clearly demonstrated. Moreover, this learning-induced survival of
      granule cells, which were born before the actual learning experience, might
      provide a molecular mechanism for the 'use it or lose it' principle.

PMID- 14670354
TI  - Two different biological configurations for long-term memory.
AB  - Long-term memory (LTM) in Hermissenda can be distinguished from consolidated long
      term memory (CLTM) by determining how long recall is retained. LTM is retained
      for approximately 1 day, while CLTM is retained for at least 3 days. During the
      transition from LTM to CLTM, the extent of retention appears to depend partially
      on how much consolidation has been completed. Several models are discussed that
      may be related to the two different manifestations of recall.

PMID- 14670355
TI  - Hippocampal CREB1 but not CREB2 is decreased in aged rats with spatial memory
      impairments.
AB  - Recent evidence has shown that abnormal signal transduction is related to non
      pathological memory impairment among aged subjects. Members of the CREB family of
      transcription factors contain enhancers (i.e., CREB1) and repressors (i.e.,
      CREB2) of transcription and interact with numerous signaling proteins to mediate
      the transition from short-term to long-term memory. In this study, quantitative
      Western blotting was used to determine the levels of CREB1 and CREB2 in
      homogenates from hippocampi of individual 6- and 24-month-old male Long-Evans
      rats trained first on a place-learning task in the Morris water maze, then on a
      transfer task. Based on spatial memory performance, aged rats were characterized
      into two groups; aged-unimpaired rats (AU) had scores within the range of the
      young (Y) and aged-impaired rats (AI) fell outside of that range. Overall, CREB1
      protein was significantly lower in aged rats in comparison with young rats.
      Aposteriori analysis showed that this difference was due to a significant
      decrease in CREB1 levels among aged-impaired rats, whereas aged-unimpaired rats
      had CREB1 levels comparable to young rats. There was no significant change in
      levels of CREB2 protein between young and aged rats. These results show that the
      dysregulation of CREB1 protein may contribute to the spatial memory deficits
      observed among some aged subjects.

PMID- 14670356
TI  - A secreted form of the beta-amyloid precursor protein (sAPP695) improves spatial
      recognition memory in OF1 mice.
AB  - The beta-amyloid precursor protein (APP) plays a central role in Alzheimer's
      disease (AD) and appears to be a multifunctional protein. Secreted forms of APP
      (sAPP) have memory-enhancing effects in certain behavioral paradigms. To
      investigate sAPP's role in spatial memory processes, we adapted a spatial
      recognition task and evaluated (1) the performance of OF1 mice after massed
      training (single 15-min acquisition session) and distributed training (three 5
      min acquisition sessions), (2) the decline of spatial recognition performance by
      introducing different delays (5min, 1, 3, and 24h) between the acquisition and
      retention phases, and (3) the effects of sAPP(695) on spatial recognition memory.
      In the present study, mice selectively reacted to a change in the spatial
      configuration of five objects. Indeed, 3min post-acquisition, mice performed
      similarly in the massed and distributed versions of the task, by re-exploring the
      two displaced objects only, whereas mice exposed to the same spatial
      configuration did not. Additionally, all mice did react to a novel object in a
      subsequent object recognition phase. Mice detected object displacements 5min, 1h,
      or 3h post-acquisition, but no more at a 24h-delay. Finally, mice treated with
      sAPP(695) intracerebroventricularly at a dose of 0.5pg/4microL/mouse, 20-min pre
      acquisition or 5-min post-acquisition, still reacted to a spatial change in
      objects position 24h post-acquisition, in marked contrast to NaCl-treated mice.
      Our data demonstrate that sAPP(695) significantly improves a form of spatial
      memory, and confirms the hypothesis of an action of this protein on early memory
      processes.

PMID- 14670357
TI  - Memory for objects and their locations: the role of the hippocampus in retention
      of object-place associations.
AB  - Computational models of hippocampal function have suggested that the hippocampus
      is involved in the formation and storage of arbitrary associations. Previous
      studies have shown that rats with hippocampal lesions are impaired in object
      place associative learning. However, few studies have examined the role of the
      hippocampus in the retention of previously learned arbitrary associations. In the
      present study, male Long-Evans rats with either cortical control or hippocampal
      lesions were tested on a task measuring the retention of previously learned
      arbitrary associations using an object-place paired-associate task. To assess
      retention, each animal was trained on the paired-associate task for 360 trials,
      then received a lesion, and was retested to examine retention of the previously
      learned associations. The results indicate that all rats learned the task prior
      to surgery. Following surgery, rats with cortical control lesions were not
      impaired in the retention of object-place associations. In contrast, hippocampal
      lesions resulted in an initial deficit in retention of the paired-associate task
      followed by recovery. Therefore, the hippocampus may play a role in the retrieval
      of previously learned arbitrary association.

PMID- 14670358
TI  - Contextual conditioning in infants, but not older animals, is facilitated by CS
      conditioning.
AB  - Context conditioning in infant Sprague-Dawley rats (postnatal days [PD] 15, 17,
      and 19), juveniles (PD 25), adolescents (PD 35), and adults (PD 71-89) was
      compared when CS conditioning did or did not occur in the context. Degree of CS
      conditioning within that context was equated across age, and separate groups at
      each age were given unpaired presentations of the CS and US within that context.
      Infants conditioned more effectively to context when CS-US pairings occurred in
      that context than when they did not, juveniles conditioned to context about
      equally with and without CS-US pairings in the context, and adolescents and
      adults conditioned less effectively to context when CS and US were paired than
      when unpaired. Adolescents had significant context conditioning despite CS-US
      pairings in the context but adults did not, and overall, context conditioning was
      strongest for adolescents. Supplementary experiments indicated that with more
      extensive conditioning experience, the infants' pattern of context conditioning
      became more similar to that of older animals, and with less conditioning
      experience the pattern of context conditioning by adults became more similar to
      that of younger animals, but infants never attained the adult pattern of context
      conditioning nor did adults attain the infant pattern. The potentiation of
      context conditioning by CS conditioning observed in infants is consistent with
      previous evidence derived from compound conditioning. Alternative explanations
      place common emphasis on infant-specific amodal processing. One views
      potentiation as a result of the greater perceived intensity of the stimulus
      compound (CS and context, in this case) during conditioning and the lesser
      generalization decrement in infants than adults when tested with a single element
      after conditioning with a compound. The other explanation emphasizes consequences
      of the redundancy inherent in intersensory compounds, within the theory of
      Bahrick and Lickliter.

PMID- 14670359
TI  - Intra-basolateral amygdala infusions of AP-5 impair or enhance retention of
      inhibitory avoidance depending on training conditions.
AB  - Previous evidence has suggested that N-methyl-D-aspartate receptors (NMDARs) in
      the basolateral amygdala (BLA) are critically involved in the acquisition of
      aversively based learning tasks. However, the role of NMDARs in the BLA in the
      consolidation of memory of aversive training has not been well elucidated. In the
      present study, the NMDAR antagonist AP-5 (1 or 3 microg) was infused into the BLA
      of male Sprague-Dawley rats immediately before, immediately after, or 6h after
      training on an inhibitory avoidance task with either a high footshock (HFS; only
      high dose of AP-5 given) or a low footshock (LFS; both doses of AP-5 given). The
      48 h retention of animals given AP-5 (3 microg) immediately before or after HFS
      training was significantly impaired compared to that of vehicle-controls. In
      contrast, the retention of rats given AP-5 (3 microg) immediately after LFS
      training was significantly enhanced compared to that of vehicle-controls. AP-5 (3
      microg) infusions administered 6h after training with either an HFS or LFS did
      not affect retention. These findings suggest that the NMDARs in the BLA are
      involved in both the acquisition and consolidation of aversive memory. In
      addition, the AP-5-induced enhancement of memory obtained with LFS training
      suggests that NMDARs in the BLA are involved in other mechanisms influencing
      synaptic transmission, in addition to their well-established role in
      neuroplasticity.

PMID- 14670360
TI  - Memory enhancement of classical fear conditioning by post-training injections of
      corticosterone in rats.
AB  - There is extensive evidence that post-training administration of the
      adrenocortical hormone corticosterone facilitates memory consolidation processes
      in a variety of contextual and spatial-dependent learning situations. The present
      experiments examine whether corticosterone can modulate memory of auditory-cue
      classical fear conditioning, a learning task that is not contingent on contextual
      or spatial representations. Male Sprague-Dawley rats received three pairings of a
      single-frequency auditory stimulus and footshock, followed immediately by a post
      training subcutaneous injection of either corticosterone (1.0 or 3.0mg/kg) or
      vehicle. Retention was tested 24h later in a novel test chamber and suppression
      of ongoing motor behavior served as the measure of conditioned fear.
      Corticosterone dose-dependently facilitated suppression of motor activity during
      the 10-s presentation of the auditory cue. As corticosterone administration did
      not alter responding after unpaired presentations of tone and shock, tone alone,
      shock alone or absence of tone/shock, the findings indicated that corticosterone
      selectively facilitated memory of the tone-shock association. Furthermore,
      injections of corticosterone given 3h after training did not alter motor activity
      during retention testing, demonstrating that corticosterone enhanced time
      dependent memory consolidation processes. These findings provide evidence that
      corticosterone modulates the consolidation of memory for auditory-cue classical
      fear conditioning and are consistent with a wealth of data indicating that
      glucocorticoids can modulate a wide variety of emotionally influenced memories.

PMID- 14670361
TI  - Ethanol impairs memory of a simple discrimination in adolescent rats at doses
      that leave adult memory unaffected.
AB  - Adolescent rats are less sensitive than adults to the hypothermic, anxiolytic,
      motor impairing, hypnotic, and lethal effects of ethanol. In vitro experiments
      nevertheless suggest that hippocampal neural activity is more affected by ethanol
      in preweanling or adolescent rats than in adults. These data are complemented by
      in vivo results showing that pretraining ethanol impairs learning in adolescent
      rats at doses that do not affect adult learning. In order to determine if
      posttraining ethanol affects memory differently in adolescents than in adults,
      Sprague-Dawley albino rats of both ages were trained in an appetitively motivated
      odor discrimination in which they were required to dig in scented sand for
      sweetened cereal reward. Immediately after training subjects received
      intraperitoneal injections of 0, 0.5, or 1g/kg ethanol (12.6%). At test, 48h
      later, subjects were presented with unbaited discriminanda and the time (s) spent
      digging in the S+ and S- was measured. Adolescents, but not adults, showed
      impaired discrimination performance if training was followed by ethanol. A
      subsequent experiment discounted the possibility that impaired adolescent
      performance was due to ethanol-induced conditioned taste or odor aversions. It
      thus appears that relative to adults, memory in adolescent rats is more strongly
      affected by ethanol in a test of appetitive conditioning that excludes ethanol's
      effects on sensory and motivational influences during the learning experience.

PMID- 14670362
TI  - A comparison of neuronal reactions during classical and instrumental conditioning
      under similar conditions.
AB  - During the elaboration of an instrumental reflex, it is not obligatory to use a
      conditioned stimulus, which signals the necessity to generate an instrumental
      reaction in order to receive reinforcement. However, the presence of a
      conditioned stimulus simplifies analysis of instrumental reaction, which in this
      case is the response to the conditioned stimulus. On the other hand, it is
      necessary to distinguish between instrumental and classical conditioning, since
      in both cases the response to a conditioned stimulus increases. We studied
      neuronal analogs of classical and instrumental conditioning in the identified
      neurons responsible for the defensive closure of the pneumostome in the Helix
      mollusk under the same conditions. During classical conditioning, a mollusk
      received punishment after a tactile stimulus. During instrumental conditioning, a
      mollusk received punishment when an identified neuron did not generate an action
      potential in response to a tactile stimulus. The appearance of a painful stimulus
      did not depend on the generation or failure of a spike in the related control
      neuron. Another tactile stimulus, which was never paired with an unconditioned
      stimulus, was used as a discriminated stimulus. We also compared the behavior of
      such identified neurons during pseudoconditioning. The experiments were carried
      out in a semi-intact preparation. We examined how responses to the tactile and
      painful stimuli changed during different forms of training. It was shown that the
      dynamics of neuronal responses to a conditioned tactile stimulus were much more
      complex during instrumental conditioning and consisted of several phases.
      Throughout a learning session, neural system consecutively acquired information
      as to which kind of learning was presented, whether a reaction of the neural
      system must be generated or inhibited and which instrumental reaction is correct.
      We have demonstrated that response to a painful stimulus during classical
      conditioning decreases after short-term initial increase. However, during
      instrumental learning, the neurons controlling instrumental action remained
      highly sensitive to the unconditioned stimulus. Meanwhile, foreign neurons
      decreased their responses to the unconditioned stimulus. We may tentatively
      conclude that classical and instrumental paradigms are fundamentally different at
      the cellular level.

PMID- 14670363
TI  - Selective improvement of strain-dependent performances of cognitive tasks by food
      restriction.
AB  - Temporary food restriction affects strain differences for behavioral phenotypes
      in the inbred strains of mice C57BL/6 (C57) and DBA/2 (DBA). Since food
      restriction is a routine procedure to motivate learning, we evaluated its
      influence on differences for spatial and non-spatial discrimination between these
      strains of mice by using two non-associative tasks: the Spatial Novelty Test
      (SNT) and the Spontaneous Object Recognition Test (SORT). The results confirmed
      the poor performance of the DBA mice in SNT. Nonetheless, DBA mice were perfectly
      able to recognize the novel object in SORT. By contrast, C57 mice were good
      performers in SNT but failed to recognize a novel object in SORT. Finally, food
      restriction selectively improved C57 performance in SNT and DBA performance in
      SORT. These results support the view that a food restricting procedure enhances
      strain differences for discrimination of configurational information.

PMID- 14670364
TI  - Intracerebroventricular effects of angiotensin II on a step-through passive
      avoidance task in rats.
AB  - A wealth of evidence indicates that angiotensin II (Ang II) is involved in
      learning and memory. However, the precise role of this peptide in these cognitive
      processes is still controversial, with data indicating either an inhibitory or an
      enhancing action. The present study was designed to further investigate the
      effects of intracerebroventricular injections of Ang II (0.5, 1 or 3nmol/5microl)
      on a step-through passive avoidance task in male adult Wistar rats. When
      administered pretraining, Ang II did not affect the acquisition of passive
      avoidance, but markedly improved avoidance performance when given before the
      retrieval test. The latter effect was observed in retest sessions performed up to
      72h after training. Administration of the peptide five minutes after training
      impaired retention of inhibitory avoidance. Therefore, Ang II may exert opposite
      effects on passive avoidance memory according to its interference with brain
      mechanisms leading to the storage or retrieval of this aversively motivated task.

PMID- 14670366
TI  - Ca2+ permeability of nicotinic acetylcholine receptors.
AB  - Nicotinic acetylcholine receptors (nAChRs) are expressed in muscle cells and
      neurons, as well as in an increasing number of other cell types. The nAChR
      channels are permeable to cations, including Ca(2+). Ca(2+) entry through nAChR
      channels has been shown to modulate several Ca(2+)-dependent cellular processes,
      such as neurotransmitter release, synaptic plasticity, and cell motility. The
      value of Ca(2+) permeability associated to a particular nAChR subtype thus
      represents an important indication for its physiological role. This review
      summarizes the quantitative data on Ca(2+) permeability obtained from several
      nAChR subtypes in native and heterologous systems. Different experimental
      approaches are compared, and the structural determinants of Ca(2+) permeability
      are discussed.

PMID- 14670367
TI  - Contribution of store-operated Ca2+ entry to pHo-dependent changes in vascular
      tone of porcine coronary smooth muscle.
AB  - Vascular smooth muscle contracts on increases of extracellular pH (pH(o)) and
      relaxes on pH(o) decreases possibly resulting from changes in transsarcolemmal
      Ca(2+) influx. Therefore, we studied store-operated Ca(2+) entry (SOCE; i.e.
      capacitative Ca(2+) entry (CCE)) during acidification (pH(o)=6.5) and
      alkalinization (pH(o)=8.0) in isolated porcine coronary smooth muscle cells
      (SMCs) by monitoring cytoplasmic Ca(2+) ([Ca(2+)](i)) and divalent cation entry
      (Mn(2+) quench) with fura-2/AM-fluorometry. Additionally, we evaluated the
      contribution of SOCE to pH(o)-dependent changes in isometric tension of porcine
      coronary smooth muscle strips. SOCE elicited in SMCs by the SERCA inhibitor BHQ
      was strongly modulated by pH(o) showing a decrease upon acidification and vice
      versa an increase upon alkalinization. BHQ-mediated tension of smooth muscle
      strips also revealed strong pH(o) dependence. In contrast, L-VOC-dependent
      tension ([K(+)](o)=20 and 40 mmol l(-1)) was remarkably less affected by pH(o)
      changes. Moreover, refilling of depleted Ca(2+) stores after repeated M(3)
      cholinergic receptor stimulation could be almost completely inhibited by SKF
      96365 and was markedly reduced by acidification and considerably enhanced by
      alkalinization pointing to a major role of SOCE in refilling. We conclude that
      vascular tone particularly responds to alterations in pH(o) whenever SOCE
      substantially contributes to the amount of activator Ca(2+) for contraction.

PMID- 14670368
TI  - Role of intracellular Ca2+ in the expression of the amiloride-sensitive
      epithelial sodium channel.
AB  - The amiloride-sensitive epithelial sodium channel (ENaC), a multimeric plasma
      membrane protein composed of alpha-, beta-, and gamma-ENaC subunits, mediates
      Na(+) reabsorption in epithelial tissues, including the distal nephron, colon,
      lung, and secretory glands, and plays a critical role in pathophysiology of
      essential hypertension and cystic fibrosis (CF). The function of ENaC is tightly
      regulated by signals elicited by aldosterone, vasopressin, agents that increase
      intracellular cAMP levels, ions, ion channels, G-protein-coupled mechanisms, and
      cytoskeletal proteins. In this paper, the effects of Ca(2+) on the expression of
      the human ENaC subunits expressed in human embryonic kidney cells (HEK-293 cells)
      were examined. Incubation of cells with increased extracellular Ca(2+) and
      treatment of cells with A23187 and thapsigargin stimulated the expression of the
      monomeric ENaC subunits. Treatment of cells with Ca(2+)-chelating agents, EGTA
      and BAPTA-AM, reduced the levels of ENaC subunit expression. The pulse-chase
      experiments suggested that a rise in the intracellular Ca(2+) increases the ENaC
      subunit expression. Immunoblot analysis using the anti-ubiquitin antibody
      indicated that ENaC undergoes ubiquitination. A correlation between the processes
      that regulate ENaC function with the intracellular Ca(2+) was discussed.

PMID- 14670369
TI  - Real-time analysis of phospholipase C activity during different patterns of
      receptor-induced Ca2+ responses in HEK293 cells.
AB  - [Ca(2+)](i) oscillations can either depend on oscillatory inositol-1,4,5
      trisphosphate (InsP(3)) formation by phospholipase C (PLC) or rely on local
      feedback mechanisms involving the InsP(3) receptor. To assess the PLC activity
      underlying carbachol-induced [Ca(2+)](i) oscillations in single HEK293 cells, we
      co-imaged [Ca(2+)](i) with fluorescent fusion proteins of protein kinase C (PKC)
      isotypes and the PH domain of PLC-delta 1 (PLC-delta 1(PH)). The translocation of
      PKC alpha-YFP in single cells followed two discrete patterns. Upon maximally
      effective agonist concentrations, a fast association and delayed dissociation
      (k(on)>k(off)) was the predominant pattern. The delayed dissociation has been
      linked to diacylglycerol formation. Upon stimulation with submaximally effective
      agonist concentrations as well as during regenerative [Ca(2+)](i) waves, we
      mainly observed short translocations with k(on) approximately equal to k(off).
      Translocation time courses and efficiencies of the diacylglycerol-sensing PKC
      epsilon-CFP and the InsP(3)/phosphatidylinositol-4,5-bisphosphate-sensing YFP-PLC
      delta 1(PH) were closely correlated. Significant PLC activity was only detectable
      upon strong receptor stimulation, which typically failed to trigger [Ca(2+)](i)
      oscillations. During [Ca(2+)](i) oscillations induced by submaximal receptor
      stimulation, YFP-PLC-delta 1(PH) did not translocate, whereas a fluorescent PKC
      epsilon fusion protein has been reported to exhibit a slow, non-oscillatory
      accumulation at the plasma membrane. We conclude that carbachol-induced
      [Ca(2+)](i) oscillations in HEK293 cells develop at low levels of presumably non
      oscillatory PLC activity.

PMID- 14670370
TI  - Inhibition of ADP-induced intracellular Ca2+ responses and platelet aggregation
      by the P2Y12 receptor antagonists AR-C69931MX and clopidogrel is enhanced by
      prostaglandin E1.
AB  - P2Y(12) antagonists such as clopidogrel and AR-C69931MX inhibit aggregation by
      antagonizing the effects of ADP at P2Y(12) receptors on platelets. Agents such as
      PGE(1) also inhibit aggregation by stimulating adenylate cyclase to produce cAMP,
      which interferes with Ca(2+) mobilization within the cell. Since one facet of
      P2Y(12) receptors is that they mediate inhibition of adenylate cyclase by ADP, it
      might be expected that P2Y(12) antagonists would interact with PGE(1). We have
      explored the effects of PGE(1) and AR-C69931MX singly and in combination on ADP
      induced intracellular Ca(2+) ([Ca(2+)](i)) responses and aggregation. PGE(1)
      alone caused parallel dose-dependent inhibition of [Ca(2+)](i) and aggregation
      responses. AR-C66931MX alone caused only partial inhibition of [Ca(2+)](i)
      despite a marked inhibitory effect on aggregation. Combinations of PGE(1) with AR
      C66931MX were found to act in synergy to reduce both [Ca(2+)](i) and aggregation.
      This effect was confirmed in patients with acute coronary syndromes by studying
      the inhibitory effects of PGE(1) on [Ca(2+)](i) and aggregation before and after
      clopidogrel. In summary, we have shown that P2Y(12) antagonists interact with
      natural agents such as PGE(1) to provide more effective inhibition of [Ca(2+)](i)
      and platelet aggregation. This would contribute to the effectiveness of P2Y(12)
      antagonists as antithrombotic agents in man.

PMID- 14670371
TI  - Calcium release from intracellular stores in rodent astrocytes and neurons in
      situ.
AB  - Endoplasmic reticular Ca(2+) stores, instrumental for intra- and intercellular
      calcium signalling, can be depleted by different receptor agonists. In the
      present study, the functional status of ER Ca(2+) stores was probed by
      cyclopiazonic acid (CPA, 10-30 microM, inhibitor of SERCA-dependent ER Ca(2+)
      uptake) and/or caffeine (20 mM, ryanodine receptor activator) in astrocytes and
      neurons of rat and mouse acute hippocampal brain slices (Stratum radiatum,
      Stratum moleculare), and in cultured astrocytes, using confocal microscopy and
      conventional Ca(2+) imaging. Astrocytes and neurons in situ, identified by their
      Ca(2+) response in K(+)-free saline (Dallwig and Deitmer [J. Neurosci. Methods
      116 (2002) 77]), had a resting cytosolic Ca(2+) level of 105 and 157 nM,
      respectively (P<0.05). CPA evoked a Ca(2+) transient, which was faster and larger
      in neurons than in astrocytes, indicating larger Ca(2+) leak of neuronal Ca(2+)
      stores. Caffeine evoked a Ca(2+) rise in most neurons (>80%), but only in less
      than 40% of astrocytes. The glial Ca(2+) transients in the presence of caffeine
      had a large and variable delay (>50 s), as compared to those in neurons (< or =10
      s), and appeared to be spontaneous and/or secondary to the neuronal Ca(2+)
      response, leading to release of neuronal transmitters. Astrocytes in culture
      responded to CPA, but never to caffeine with a Ca(2+) rise. Our results indicate
      that astrocytes, in contrast to neurons, lack caffeine-sensitive Ca(2+) stores,
      and have a relatively smaller leak from CPA-sensitive Ca(2+) stores than neurons.

PMID- 14670372
TI  - InsP3 receptor type 2 and oscillatory and monophasic Ca2+ transients in rat
      adrenal chromaffin cells.
AB  - Muscarinic receptor stimulation induced oscillatory and monophasic Ca(2+)
      transients in rat adrenal chromaffin cells in the absence of external Ca(2+). As
      this Ca(2+) mobilization may be mediated by InsP(3), we first explored types of
      InsP(3) receptors and their intracellular distribution in chromaffin cells. The
      InsP(3) receptor type 1 was not immunodetected in precipitates of adrenal medulla
      homogenates and in dissociated adrenal chromaffin cells, whereas an anti-type 3
      mAb recognized a faint band with about 250 kDa, but no significant immunoreaction
      was visible in chromaffin cells. The anti-type 2 mAb strongly detected a band
      with about 220 kDa and the immunoreaction was observed perinuclearly and at the
      cell periphery. These results indicate that InsP(3) receptor type 2 is
      predominant in chromaffin cells. The oscillatory and monophasic Ca(2+) transients
      were reproduced in simulation based on a three-state kinetic model (shut, open,
      and inactivated states). Ca(2+) ions were found experimentally and theoretically
      to turn over rapidly between stores and the cytosol during stimulation. The
      results suggest that InsP(3) receptor type 2 is responsible for both oscillatory
      and monophasic Ca(2+) transients and that change in mode of Ca(2+) responses may
      be accounted for by the kinetic property of the type 2 receptor.

PMID- 14670373
TI  - PPF1 inhibits programmed cell death in apical meristems of both G2 pea and
      transgenic Arabidopsis plants possibly by delaying cytosolic Ca2+ elevation.
AB  - PPF1 encodes a putative calcium ion carrier that affects the flowering time of
      transgenic Arabidopsis by modulating Ca(2+) storage capacities in chloroplasts of
      a plant cell. In the current work, we found that differential expression of PPF1
      might affect processes of programmed cell death (PCD) since DNA fragmentation was
      detected in senescencing apical buds of long day-grown G2 pea (Pisum sativum L.)
      plants, but was not in non-senescencing short day-grown counterparts at all
      growth stages. An animal inhibitor of caspase-activated DNase (ICAD) homologue
      was detected in short day-grown plant continuously throughout the whole
      experiment and only in early stages of long day-grown pre-floral G2 pea apical
      buds. DNA fragmentation was significantly inhibited in apical meristems of
      transgenic Arabidopsis that over-expressed the PPF1 gene when compared to that of
      either wild-type control or to PPF1 (-) plants. The expression of ICAD-like
      protein decreased to undetectable level at 45 dpg in apical tissues of PPF1 (-)
      Arabidopsis, which was much earlier than that found in PPF1 (+) or wild-type
      controls. In epidermal cells of PPF1 (-) plants, we recorded significantly
      earlier calcium transient prior to PCD. We suggest that the expression of PPF1, a
      chloroplast localized Ca(2+) ion channel may inhibit programmed cell death in
      apical meristems of flowering plants by keeping a low cytoplasmic calcium content
      that might inhibit DNA fragmentation in plant cells.

PMID- 14670374
TI  - Correction of image instability in confocal microscopy using image realignment.
      Effects on the analysis of intracellular calcium.
AB  - Using confocal microscopy, we have examined the increases in [Ca(2+)](i) evoked
      by sodium channel toxins in cells labelled with the fluorescent dye INDO-1. We
      describe a new image analysis method that improves the detection of region
      specific, toxin-induced patterns of change of intracellular calcium. This method
      is based on correction of global image motion followed by calculation of the
      strength of correlation between calcium changes in "seed" or reference pixels
      chosen to represent different regions of cells and those in other regions of the
      image. When the selected "seed" pixel was chosen to be in either varicosities or
      neurites, correlations were detected in the same regions of other cells as well
      as in the soma, indicating specific but spatially distinct patterns of behaviour.
      Control images (without changes in [Ca(2+)](i)) did not reveal significant
      interpixel correlations. The ability to recognize correlated patterns of calcium
      change in different regions of cells was greatly improved by correction for
      global motion.

PMID- 14670375
TI  - Validity of the Children's Category Test-Level 1 after pediatric traumatic brain
      injury.
AB  - The performance of 38 5-8-year-old children with traumatic brain injury (TBI) on
      the Children's Category Test-Level 1 (CCT-1; ) was investigated in order to
      examine the criterion validity of the component subtests. Only subtests III and V
      varied in a consistent and meaningful manner with levels of injury severity and
      post-injury psychometric intelligence. In contrast, 21% of the sample performed
      at chance level on subtest IV, a task that did not demonstrate any criterion
      validity. It is concluded that when a substantial proportion of the total errors
      (e.g., >/=50%) on the CCT-1 pertain to items from subtest IV, interpretation of
      the composite summary T score may not be valid.

PMID- 14670376
TI  - Mild cognitive impairment: new neuropsychological and pharmacological target.
AB  - Mild cognitive impairment (MCI) is increasingly being conceptualized in the
      literature as a cognitive disturbance representing a transitional phase between
      normal aging and dementia. The operational definitions of MCI provide an
      opportunity for neuropsychologists to detect subtle deficit and monitor cognitive
      status sequentially in order to determine rate and degree of progression. More
      importantly, clinical and neuropsychological studies are needed that can better
      characterize which MCI patients are at greatest risk for conversion to dementia.
      Preliminary data has also designated MCI as a potential indicator for initiation
      of pharmacotherapy, with the objective of decelerating rate of progression to
      dementia. Current criteria and clinical issues related to MCI are discussed, with
      the objective of better familiarizing clinicians with this syndrome and fostering
      ongoing investigations.

PMID- 14670377
TI  - The differential effect of conation on intelligence test scores among brain
      damaged and control subjects.
AB  - Conation, or the ability to apply effective effort in completing a task over
      time, has been shown to be impaired in brain-damaged subjects. Various
      intelligence tests differ in the apparent extent to which they require conative
      ability. In this study we compared results earned by brain-damaged and control
      groups on three measures of intelligence: Wechsler Verbal IQ (VIQ), Wechsler
      Performance IQ (PIQ), and the Henmon-Nelson Test (HNT) of Mental Ability. Test
      scores were converted to T-score distributions for the combined groups in order
      to delete possible effects of differences in standardization procedures and the
      normative samples on which IQ scores were generated. The degree of impairment
      shown by the brain-damaged subjects was in direct relationship to the extent to
      which the three intelligence measures appear to require conation. The results
      support a generalization that intelligence tests that require a greater conative
      ability tend to produce lower scores for brain-damaged persons, as compared to
      controls, than do intelligence tests that are less demanding of conation.

PMID- 14670378
TI  - Head injury and the ability to feign neuropsychological deficits.
AB  - This study investigated the possibility that head-injured patients, by virtue of
      their exposure to medical and legal evaluations, are better able to feign
      deficits than controls. Both internal and external validity issues were addressed
      in a malingering simulation using 46 moderately to severely head injured and 46
      matched control subjects who were administered a battery of neuropsychological
      and motivational tests under standard or malingering instructions. Results showed
      no significant interaction between malingering instructions and head injury
      status on commonly used motivational tests or neuropsychological tests, nor were
      the head injured malingerers better able to avoid detection using established
      cutting scores on motivational tests. These results suggest that head injured
      individuals are no more able to feign neuropsychological deficits successfully
      than non-head injured individuals.

PMID- 14670379
TI  - Detection of neurocognitive feigning: development of a multi-strategy assessment.
AB  - Neuropsychological assessments can be completely invalidated by persons
      successfully feigning neurocognitive impairment. The current investigation
      examines via a research measure, the Test of Cognitive Abilities (TOCA), the
      usefulness of multiple detection strategies for the classification of
      neurocognitive feigning. Using a simulation design with a manipulation check and
      both positive and negative incentives, two groups of simulators (Cautioned and
      NonCautioned) were compared with brain-injured patients and nonimpaired controls.
      Among detection strategies, Magnitude of Error (hit rate=.94) was highly
      effective, while Floor Effect (hit rate=.80) and Reaction Time (hit rate=.85)
      were moderately effective. When presented with complex strategies, the cautioning
      of simulators did not improve their performances.

PMID- 14670380
TI  - Normative data for elderly African Americans for the Stroop Color and Word Test.
AB  - The Stroop Color and Word Test is a measure of executive function that is
      commonly used in neuropsychological evaluations, but for which there are
      currently no normative date for elderly African American individuals. The present
      investigation examined the influence of demographic characteristics on this
      measure in a community-dwelling sample of 236 elderly African American adults (60
      84 years of age). Age, education, gender, and the education by gender interaction
      were found to affect performance on the Stroop Color and Word Test tasks. Based
      on these results, normative tables for Stroop Color and Word Test scores,
      stratified by age and with score adjustments for education and gender, are
      provided.

PMID- 14670381
TI  - The effects of motivation, coaching, and knowledge of neuropsychology on the
      simulated malingering of head injury.
AB  - Two student groups, introductory psychology (n=91) and advanced neuroscience
      (n=34) undergraduates, were asked to malinger a head injury on Rey's 15-Item Test
      (FIT) and Dot Counting Test (DCT). The participants were randomly assigned to one
      of three motivation conditions (no motivation given, compensation, avoidance of
      blame for a motor vehicle accident) and to one of three coaching conditions (no
      coaching, coaching post-concussive symptoms, coaching symptoms plus warning of
      malingering detection). Analyses revealed a MotivationxStudent Group interaction
      on the FIT, indicating that the advanced neuroscience students, particularly when
      in the compensation condition, malingered the most flagrantly. On the DCT, main
      effects for motivation and coaching on the qualitative variables and a
      MotivationxCoaching interaction on the accuracy variables indicated that those in
      the compensation condition performed the most poorly, and that coaching plus
      warning only tempers malingering on memory tasks, not timed tasks.

PMID- 14670382
TI  - Detecting dementia with the Hopkins Verbal Learning Test and the Mini-Mental
      State Examination.
AB  - The Hopkins Verbal Learning Test (HVLT) and the Mini-Mental State Examination
      (MMSE) were administered to 323 non-demented elderly and 70 individuals who meet
      DSM-IV criteria for dementia in order to compare the validity of these two
      measures for detecting mild dementia and for the two most common dementia
      subtypes, Alzheimer's disease (AD) and vascular dementia (VaD). The study was
      conducted in an elderly, ethnically diverse community-dwelling population.
      Sensitivity, specificity, positive and negative predictive values were calculated
      over a range of clinically relevant cut scores for each test. We analyzed the
      influence of age, education, reading ability and sex on test performance using
      logistic regression models. When sensitivity is held constant at 0.69, the
      specificity for the HVLT total recall was 0.89 and the MMSE 0.82 for all
      dementias (P=.10). Age, sex and education did not significantly influence test
      performance for either test in this sample. Results were similar for AD and VaD.
      However, while adding a measure of reading ability to the regression models did
      not affect the overall dementia model, it resulted in improved specificities when
      combined with the MMSE for AD and combined with the HVLT for VaD. Additional
      tests such as reading ability can improve discrimination of dementia subtypes.
      The modest sensitivity of either the HVLT or the MMSE alone suggests that further
      neuropsychological evaluation is required to confirm dementia diagnosis.

PMID- 14670383
TI  - Memory functioning in children with traumatic brain injuries: a TOMAL validity
      study.
AB  - Traumatic brain injury (TBI) leads the causes of death and disability among
      children and adolescents. Despite the prevalence of TBI among children, few
      studies have examined memory in children. The purpose of this study was to
      compare memory functioning, as measured by the Test of Memory and Learning
      (TOMAL), of children with and without TBI and with moderate and severe TBI to
      determine if differences existed. Of the 140 participants, 70 had sustained a
      head trauma and 70 served as controls. The results indicated that, when the TBI
      and control group were compared, significant differences were found on all of the
      TOMAL indexes. With the exception of the verbal delayed recall items, significant
      differences were demonstrated on all the TOMAL subtests. No differences were
      identified when moderate and severe groups were compared. These findings further
      the understanding of memory following pediatric TBI, as well as have implications
      for interventions with this population.

PMID- 14670384
TI  - Do reaction time measures enhance diagnosis of early-stage dementia of the
      Alzheimer type.
AB  - Reaction times (RT) typically are slower in demented individuals than in healthy
      older people, but it is unclear if this deficit is useful in diagnosing
      Alzheimer's disease, particularly in its early stages. In this study we compared
      131 nondemented, 73 very mildly demented, and 45 mildly demented individuals on
      simple, choice, and choice with distraction RT tasks. Less than half of the
      demented individuals could be classified correctly using the RT measures in a
      discriminant function analysis. In addition, the RT measures did not add
      significantly to correct classification achieved by a previously identified brief
      battery of standard neuropsychological tests including immediate prose recall,
      confrontation naming, and digit symbol substitution (Storandt & Hill, 1989); that
      battery identified 81% of the very mild group and 96% of the mild group as
      demented. Although substantial slowing of RT may occur in some people in the
      early stages of dementia, it is far from universal, whereas deficits in other
      cognitive functions are.

PMID- 14670385
TI  - The effect of depression and anxiety on the TOMM in community-dwelling older
      adults.
AB  - Tests of possible malingering are in increasing demand among neuropsychologists.
      The Test of Memory Malingering (TOMM) is resistant to many neurological
      conditions, including traumatic brain injury, dementia, and aphasia. Less clear
      is the impact of psychological conditions on TOMM performance. This study
      examined a sample of community-based older adults (55-75) to determine whether
      scores on the TOMM are influenced by the presence of symptoms of depression or
      anxiety, as measured by the Beck Depression Inventory (BDI) and State-Trait
      Anxiety Inventory (STAI), respectively. The results indicate that, regardless of
      BDI or STAI scores, all subjects scored above 45 correct out of 50 on TOMM Trial
      2. These findings demonstrate that depression and anxiety levels in an older
      community-dwelling sample do not negatively affect performance on the TOMM.

PMID- 14670386
TI  - The Adjusting-Paced Serial Addition Test (Adjusting-PSAT): thresholds for speed
      of information processing as a function of stimulus modality and problem
      complexity.
AB  - A modified computer version of the PASAT (Adjusting-PSAT; ) is described that
      measures speed of information processing and working memory by means of a
      temporal threshold rather than number of correct responses. This is accomplished
      by making the duration of the interval between numbers depend on the correctness
      of responding-a correct response decreases the interval between digits and an
      incorrect response increases the interval. Modality of presentation (visual and
      auditory) was factorially combined with problem difficulty (answers between 2-10
      or 2-18). Performance of 60 healthy student volunteers on the Adjusting-PSAT was
      compared to that obtained on several traditional neuropsychological measures
      (Digit Span, Trail Making Test, and Symbol Digit Modality Test) and on a test of
      basic addition skills. The visual version of the test produced a lower threshold
      than did the auditory version, but problem difficulty did not produce a
      significant effect. Of the neuropsychological tests, Trails-B (TMT-B) was most
      highly correlated with thresholds. However, regression analyses revealed that
      math ability accounted for more variance than did TMT-B. The clinical
      implications of these finding are discussed.

PMID- 14670389
TI  - Clinical cognition and embodiment.
AB  - I first identify two different distinctions: between Cartesian cognition and
      embodied cognition, and between calculative rationality and intuitive know-how. I
      then suggest that, in the nursing literature, these two distinctions are run
      together, to create an opposition between 'Cartesian rationality' and 'embodied
      know-how'. However, it is vital to keep the two distinctions apart, because
      'embodied knowing' is very frequently rational. In separating the idea of
      embodied cognition from non-rational intuition, I show how 'embodiment' leads to
      the concepts of distributed cognition and distributed expertise. This has
      extensive and important implications for how we understand clinical cognition in
      nursing.

PMID- 14670390
TI  - Increasing the visibility of coding decisions in team-based qualitative research
      in nursing.
AB  - OBJECTIVES: To examine the use of the multi-rater Kappa measure of agreement
      (Nonparametric Statistics for the Behavioural Sciences, McGraw Hill, New York,
      1988) in team based, mixed method, qualitative nursing research. DESIGN: The
      article presents an illustrative description of the application of the
      qualitative coding procedure and associated multi-rater Kappa measurement at four
      time points in 9 months amongst a five person health services research team. MAIN
      OUTCOME MEASURES: The multi-rater Kappa statistic. This is a measure of the
      extent to which observers achieve possible agreement beyond any agreement
      expected to occur by chance alone. RESULTS: Closeness to primary qualitative
      research data, working relationships over time, and focused research team
      discussion can all lead to greater agreement and convergence at the level of
      descriptive coding. The method of measuring agreement between groups of coders
      was easily applied and appeared a feasible option for similar research projects
      wishing to demonstrate transparency in their coding procedures. CONCLUSION:
      Measuring agreement beyond chance by the multi-rater Kappa statistic has some
      utility for research teams whose qualitative coding tasks are primarily
      descriptive. The method offers a standard and transparent approach for
      demonstrating agreement between coders and should be a feature of qualitative
      research reporting where appropriate.

PMID- 14670391
TI  - Anglo-American nursing theory, individualism and mental health care: a social
      conflict perspective.
AB  - This paper uses social conflict theory to reconsider the relationship of American
      nursing theory and individualised mental health care in the UK. It is argued that
      nursing theory has developed within a context of 'American dream' individualism,
      and that this ideology may be problematic for some UK mental health nurses and
      service users whose values and beliefs are those of different socio-political
      traditions. The paper explores the historical background of Anglo-American
      nursing theory, and then uses conflict theory to generate challenging
      propositions about the culture bias and political instrumentality of
      individualised care in mental health settings. In so doing, it critiques the
      'scientific' and 'liberal' preconceptions of individualised care which have
      dominated mental health care policy for over a decade.

PMID- 14670392
TI  - Predicting post-surgical cognitive disturbance in older Taiwanese patients.
AB  - The purpose of this study was to test a theoretical model to understand the
      influences of six predicting variables in post-surgical cognitive disturbance in
      older Taiwanese patients after elective surgery. The data were collected in a
      medical center in Taipei, Taiwan. Ninety-three patients were included in the
      final analysis. The findings showed that cognitive function at admission
      (beta=0.50, p<0.001), physical function at admission (beta=-0.34, p<0.001), and
      physiological stability (beta=-0.21, p<0.01) had direct effects on post-surgical
      cognitive disturbance. Physical function and cognitive function at admission also
      affected post-surgical cognitive disturbance indirectly through physiological
      stability. These variables accounted for 67% of the total variance of post
      surgical cognitive disturbance. The findings from this study suggest that a
      careful and systematic assessment of the patient's condition at the time of
      admission is important. It is necessary to monitor and correct these variables at
      admission or before surgery to prevent or reduce the impact of post-operative
      delirium. It is also necessary to monitor these variables during the hospital
      stay to help nurses to distinguish the etiology of delirium. In each case,
      knowing when confusion is more likely to occur can assist in focusing more
      appropriate and effective efforts at detection, thereby reducing the consequences
      associated with confusion.

PMID- 14670393
TI  - What is social capital and how does it relate to health?
AB  - During the last 25 years, a new term has cropped up in social sciences, social
      capital. In the last 10 years, this term acquired a new dimension which relates
      it to health. Following an analysis of theoretical issues surrounding social
      capital and social support, recent research is used to illustrate how these are
      affecting health. It is argued that more theoretical development is needed before
      social capital can be used to form a new community nursing practice. Until then,
      the ideas of social capital (social contact, companionship, etc.) may guide our
      mode of operation during nursing interventions.

PMID- 14670394
TI  - Parents' perceptions of their infant's pain experience in the NICU.
AB  - Despite numerous advances in the recognition, assessment, and management of pain
      in neonates over the past two decades, there has been limited improvement in the
      knowledge base regarding parental responses to their infant's pain. This study
      examined parents' views of their experiences observing and coping with their
      infant's pain in the neonatal intensive care unit (NICU). Twelve participants
      were recruited using purposive sampling from two groups: (a) parents who had
      infants currently receiving care in the NICU (n=6); and (b) parents whose infants
      had been discharged from the NICU and were enrolled in the outpatient follow-up
      clinic at each hospital (n=6). An exploratory, semi-structured format was used to
      interview parents individually (n=5) or in focus groups (n=7) regarding their
      infant's clinical course, infant pain experiences, and the parenting experience
      during and after the NICU stay. Thematic content analysis was used to develop
      conceptual categories. Two broad themes were identified: (a) infant pain as a
      source of parental distress and (b) relief of parental distress due to infant's
      pain.

PMID- 14670395
TI  - Empowerment of patients with end-stage renal disease--a randomized controlled
      trial.
AB  - The purpose of the study is to investigate the effectiveness of an empowerment
      program on empowerment level, self-care self-efficacy and depression in patients
      with end-stage renal disease. The study was a randomized controlled trial;
      qualified patients in two dialysis centers of major hospitals in southern Taiwan
      were randomly assigned into an empowerment group (n=25) and a control group
      (n=25). The empowerment program included identification of problem areas for self
      management; exploration of emotions associated with these problems; development
      of a set of goals and strategies to overcome these problems to achieve these
      goals; creation and implementation of behavioral change plans; and stress
      management. The outcomes measured were the Empowerment Scale, the Strategies Used
      by People to Promote Health and the Beck Depression Inventory. Data were
      collected at baseline and 6 weeks following intervention. Primary statistical
      analysis was by means of t-test and analysis of covariance. The results indicated
      that scores of the empowerment (t(48)=6.54, p<0.001), self-care self-efficacy
      (F(1,47)=10.82, p=0.002) and depression (t(48)=2.49, p=0.03) in the empowerment
      group have a significantly greater improvement than the control group.

PMID- 14670396
TI  - Determination of the usage of body mechanics in clinical settings and the
      occurrence of low back pain in nurses.
AB  - This explorative study was designed to identify the usage of body mechanics in
      clinical settings and the occurrence of low back pain in nurses. The sample was
      composed of 56 nurses who work on the medical, surgical, emergency and intensive
      care units of a state hospital in Bolu, Turkey. Data collected through
      observation and interviews were evaluated using percentages, Chi-square and Mann
      Whitney U tests. Results of the study showed that the majority of the nurses
      (87.5%) experienced low back pain at some time in their lives. Among the
      contributing factors for back pain, the relationship between wearing high heels,
      heavy lifting and back pain was significant statistically. According to the
      observations, the majority of the nurses used body mechanics correctly while
      sitting (53.6%), standing (58.7%), carrying (64.3%), pulling or pushing (79.4%),
      moving the patient to the side of the bed without an assistant (53.4%), moving
      the patient to a sitting position in bed (71.4%) and assisting the patient to a
      standing position (66.6%). However 57.1% of the nurses lifted and 82% extended
      incorrectly. The conclusion from this research was that some of the nurses do not
      use body mechanics correctly and the majority have low back pain.

PMID- 14670397
TI  - Perception of stressors by patients and nurses of critical care units in Hong
      Kong.
AB  - The frightening experience in critical care units, whether it be associated with
      the disease process or related to the critical care environment, has an important
      impact on clients' recovery and rehabilitation. A comparative descriptive study
      was conducted in the critical units of two major hospitals in Hong Kong to assess
      the perception of stressors by patients and nurses. A Chinese version of the
      Intensive Care Unit Environmental Stressor Scale (ICUESS) was used. Significant
      similarities and differences were noted between patients and nurses on their
      perceptions of stressors in the critical care environment. Critical care nurses,
      apart from maintaining their efforts to minimize the negative effects of the
      stressful critical care environment, needed to equally focus on the patients'
      psychological needs through measures in re-establishing patients' self-control
      and minimizing the emotional stress.

PMID- 14670398
TI  - Workplace stressors, ways of coping and demographic characteristics as predictors
      of physical and mental health of Japanese hospital nurses.
AB  - Role stress has always been a concern for nurses and health care administrators.
      Most research, however, on role stress in nurses has taken place in Western
      cultures. Limited research in the area has taken place in Asian cultures and
      particularly in the country of Japan. Since the role of the hospital nurse in
      Japan is vastly different from the role of the hospital nurse in Western cultures
      and select Asian cultures, it is unclear what part workplace stressors, coping
      mechanisms and demographic characteristics play in the physical and mental health
      of Japanese hospital nurses. Therefore, this study chose to examine, in Japanese
      hospital nurses: (a) the relationships among various workplace stressors, ways of
      coping, demographic characteristics, and physical and mental health; and (b)
      which workplace stressors, coping mechanisms and demographic characteristics were
      the best predictors of both physical and mental health. Data were obtained from
      310 nurses who completed four questionnaires. Numerous significant correlations
      were found among the variables. Workload and number of people living in the
      household were found to be the best predictors of physical health. The best
      predictors of mental health were likelihood to leave the current nursing
      position, lack of support in the workplace, and escape-avoidance coping.

PMID- 14670399
TI  - Acupressure and fatigue in patients with end-stage renal disease-a randomized
      controlled trial.
AB  - The purpose of the study is to investigate the effectiveness of acupressure on
      fatigue in patients with end-stage renal-disease (ESRD). The study was a
      randomized control trial; qualified patients were randomly assigned into
      acupressure group, sham group or control group. A total of 106 participants were
      included in the study. The measures included the revised Piper Fatigue Scale
      (PFS), VAS of Fatigue, the Pittsburgh Sleep Quality Index and the Beck Depression
      Inventory. Data of fatigue measures were collected at pretreatment and a week
      following treatment. Sleep quality and depression were collected during post-test
      only. The statistical methods included the descriptive statistics, one-way ANOVA,
      ANCOVA, and repeated-measures ANOVA. ANCOVA that adjusted for differences in
      baseline fatigue scores (PFS), post-test of depression and sleep quality, result
      was significant, F(2,100)=3.99, p=0.02. Post-hoc tests revealed that patients in
      the acupressure group were significantly having lower scores of fatigue than
      patients in the control group. ANCOVA results also significant for VAS of Fatigue
      among groups, F(2,100)=5.63, p=0.003. Comparisons indicated that there were
      significant differences between the acupressure group and the control group
      (p=0.01) and between the sham group and control group (p=0.003). Predialysis
      fatigue was assessed routinely by using a rating of 0-10. Repeated-measures ANOVA
      results demonstrate the group main effect was significant in the perceived
      fatigue (F(2,88)=19.46, p<0.001). Follow-up tests indicated there were
      significant differences between the acupressure group and the control group
      (p<0.001) and between the sham group and control group (p<0.001). The study
      provided an alternative method for health care providers to managing ESRD
      patients with fatigue.

PMID- 14670400
TI  - A test instrument for palliative care.
AB  - This article describes a methodological study concerning the development of a
      test instrument that can be used for measuring the effects of a course in
      palliative care on registered nurses and licensed practical nurses. This test
      instrument is comprised of two parts: an expertise and insight test and a self
      efficacy instrument and is tested in three panels. The expertise and insight test
      appears to be usable for measuring the effects of a course in palliative care.
      The reliability and validity of the test were found to be adequate for evaluation
      of the effects of a post-basic palliative care course. The generality of the self
      efficacy instrument was reduced because high-scoring items in the area of
      communication had to be removed. Moreover, the scores of the various categories
      of respondents discriminate less than expected on the basis of their previous
      education and the test results. Many respondents, regardless of their background,
      believed themselves to have a high level of competency. The self-efficacy
      instrument must therefore be used cautiously.

PMID- 14670401
TI  - Calculating IOL power in eyes that have had refractive surgery.

PMID- 14670402
TI  - Effect of cataract surgery on IOP after trabeculectomy.

PMID- 14670403
TI  - Penetration of topical ciprofloxacin into the aqueous.

PMID- 14670404
TI  - Risk for bacterial endophthalmitis after cataract extraction.

PMID- 14670405
TI  - Foreign objects in clear corneal cataract surgery wounds.

PMID- 14670406
TI  - Peribulbar block without sedation.

PMID- 14670407
TI  - Conjunctival ballooning during scleral tunnel phacoemulsification.

PMID- 14670408
TI  - Removing silicone oil.

PMID- 14670409
TI  - Consultation section: refractive surgical problem.

PMID- 14670410
TI  - Pop-and-chop nucleofractis.
AB  - Horizontal chopping is effective for endocapsular nucleofractis. We describe pop
      and chop, a variant of chopping that enables an easy first crack and initial
      segment removal. It involves partial extracapsular prolapse of the nucleus prior
      to the initial chop. It is particularly useful when hydrodissection results in
      partial prolapse of the lens nucleus so that it is wedged into the anterior
      capsule opening. It is also helpful when beginning surgeons are learning phaco
      chop.

PMID- 14670411
TI  - Iridectomy of the anterior iris stroma using the vitreocutter during
      phacoemulsification in patients with iridoschisis.
AB  - We present a technique to manage iridoschisis. This technique for anterior
      iridectomy of the affected iris fibers avoids intraoperative obstruction of the
      phaco tip and prevents postoperative complications such as corneal decompensation
      and glaucoma. Before the capsulorhexis is created, a vitreocutter is inserted in
      the anterior chamber and used to cut the iris strands at the site of the
      iridoschisis, making an anterior sectorial stromal iridectomy and preserving the
      iris pigment epithelium. Phacoemulsification is then performed. After the pupil
      is constricted with carbacol, remnants of the loose anterior iris fibers are
      excised with the vitreocutter and the scleral incision is sutured.

PMID- 14670412
TI  - Use of a wick to deliver preoperative mydriatics for cataract surgery.
AB  - Before cataract surgery at our institution, we traditionally dilated the pupils
      with 5 drops: proparacaine 0.5%, cyclopentolate 1%, phenylephrine 2.5%,
      flurbiprofen sodium 0.03% (Ocufen), and ofloxacin 0.3% (Ocuflox) at 15-minute
      intervals given 3 times. This was work intensive for the nursing staff. Since
      September 2000, we have used a wick soaked in a dilating mixture containing
      cyclopentolate 1%, phenylephrine 2.5%, diclofenac sodium 0.1% (Voltaren), and
      Ocuflox. Use of the wick has been beneficial and time saving to hospital staff.

PMID- 14670413
TI  - Intraocular lens power calculation after corneal refractive surgery: double-K
      method.
AB  - PURPOSE: To determine the accuracy of a method of calculating intraocular lens
      (IOL) power after corneal refractive surgery. SETTING: Department of
      Ophthalmology, Hospital de Gipuzkoa, San Sebastian, Spain. METHODS: The SRK/T
      formula was modified to use the pre refractive surgery K-value (Kpre) for the
      effective lens position (ELP) calculation and the post refractive surgery K-value
      (Kpost) for IOL power calculation by the vergence formula. The Kpre value was
      obtained by keratometry or topography and the Kpost, by the clinical history
      method. The formula was assessed in 9 cases of cataract surgery after laser in
      situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) in which all
      relevant data were available. Refractive results of the standard SRK/T and the
      double-K SRK/T were compared statistically. RESULTS: The mean IOL power for
      emmetropia and the achieved refraction (mean spherical equivalent [SE]),
      respectively, were +17.85 diopters (D) +/- 3.43 (SD) and +1.82 +/- 0.73 with the
      standard SRK/T and +20.25 +/- 3.55 D and +0.13 +/- 0.62 D with the double-K
      SRK/T. No case in the standard SRK/T group and 6 cases (66.66%) in the double-K
      group achieved a +/-0.5 D SE. CONCLUSION: Double-K modification of the SRK/T
      formula improved the accuracy of IOL power calculation after LASIK and PRK.

PMID- 14670414
TI  - Accommodation obtained per 1.0 mm forward movement of a posterior chamber
      intraocular lens.
AB  - PURPOSE: To clarify the amount of accommodation per 1.0 mm forward movement of a
      posterior chamber intraocular lens (IOL). SETTING: Department of Ophthalmology,
      Nara Medical University, Nara, Japan. METHODS: A ray-focusing equation of
      pseudophakic eyes was obtained with the ray-tracing method using Mathematica((R))
      computer software (Wolfram). At first, it was assumed that the anterior radius of
      curvature of the cornea was 7.7 mm, the thickness was 0.5 mm, and the refractive
      index was 1.3375, and an AcrySof IOL (Alcon) was implanted in the capsular bag.
      Anterior and posterior radii of curvature and IOL thickness data were provided
      from the manufacturer and inserted in the equation. Next, the amount of
      accommodation per 1.0 mm of forward movement of a posterior chamber IOL was
      calculated under the assumption that the axial length (AL) varied from 21.0 to
      27.0 mm and the implanted IOL from 30.0 to 11.0 diopters (D). The AL was fixed at
      24.0 mm, and the anterior radius of curvature was varied from 6.5 to 9.5 mm and
      the IOL from 10.0 to 30.0 D. Similar calculations were then performed. RESULTS:
      Under the assumption of a fixed corneal anterior radius of curvature of 7.7 mm,
      when the AL was 24.0 mm and the implanted IOL 20.0 D, 1.0 mm of forward IOL
      movement corresponded to 1.3 D of accommodation. When the AL was 21.0 mm and a
      the IOL 30.0 D, 1.0 mm of forward IOL movement corresponded to 2.3 D of
      accommodation. When the AL was 27.0 mm and the IOL 11.0 D, 1.0 mm of forward IOL
      movement corresponded to 0.8 D of accommodation. Similarly, when the anterior
      radius of corneal curvature was varied from 6.5 to 9.5 mm and the IOL from 10.0
      to 30.0 D and the AL was fixed at 24.0 mm, 1.0 mm of forward IOL movement
      corresponded to 0.5 to 1.9 D of accommodation. CONCLUSIONS: Accommodation
      obtained per 1.0 mm of forward IOL movement varied with AL from 0.8 D in a long
      eye to 2.3 D in a short eye. It also varied with the corneal power. Thus, one
      should not state that 1.0 mm of forward IOL movement always corresponds to a
      certain amount of diopters of accommodation.

PMID- 14670415
TI  - Effect of intraocular lens implantation on visual acuity, contrast sensitivity,
      and depth of focus.
AB  - PURPOSE: To determine the role of spherical and irregular aberrations in the
      optics of the natural eye and after intraocular lens (IOL) implantation in terms
      of visual acuity, contrast sensitivity, and depth of focus. SETTING: Laboratory
      of Experimental Ophthalmology, University of Groningen, Groningen, The
      Netherlands. METHODS: Visual acuity and defocus-specific contrast sensitivity in
      11 pseudophakic patients (IOL group) and 27 age-matched phakic subjects were
      compared. The results were obtained psychophysically. Spherical and irregular
      aberrations were subsequently estimated by comparing the measured myopic shift
      (optimum focus of contrast sensitivity at 4 cycles per degree [cpd] compared to
      that at 16 cpd) and depth of focus with those of theoretical eye models with
      varying amounts of irregular and spherical aberrations. RESULTS: The best
      corrected visual acuity and best corrected contrast sensitivity in the IOL group
      did not significantly differ from that in the phakic group. The depth of focus
      was larger in the IOL group at a pupil diameter of 6.0 mm (P<.05). Comparison
      with theoretical eye models suggested a higher amount of spherical aberration in
      the IOL group; irregular aberration was almost the same in both groups.
      CONCLUSIONS: There was a higher amount of spherical aberration in the IOL group,
      related to a larger depth of focus, without loss of contrast sensitivity at
      optimum focus or loss of visual acuity. This might contribute to better quality
      of vision in pseudophakic subjects than in presbyopic phakic subjects.

PMID- 14670416
TI  - Effect of methods of myopia correction on visual acuity, contrast sensitivity,
      and depth of focus.
AB  - PURPOSE: To psychophysically measure spherical and irregular aberrations in
      patients with various types of myopia correction. SETTING: Laboratory of
      Experimental Ophthalmology, University of Groningen, Groningen, The Netherlands.
      METHODS: Three groups of patients with low myopia correction (spectacles, soft
      contact lens, and Intacs) and 4 groups with high myopia correction (spectacles,
      rigid contact lens, Artisan claw lens, and laser in situ keratomileusis [LASIK])
      had through-focus contrast sensitivity measurements to establish the myopic shift
      and depth of focus. From these 2 parameters, spherical and irregular aberrations
      were determined using theoretical eye models and geometric optics. Visual acuity,
      stray light, and predictability were also studied. RESULTS: There were no
      differences in best corrected visual acuity (BCVA) or best corrected contrast
      sensitivity between the low myopia groups. The Intacs group had a significantly
      larger depth of focus (P<.05). The results in the soft contact lens group were
      comparable to those in a human eye model with an average amount of spherical and
      irregular aberrations. The LASIK group had worse uncorrected visual acuity (UCVA)
      and best corrected contrast sensitivity than the spectacles, rigid contact lens,
      and Artisan claw lens groups (P<.05) due to the amount of spherical and irregular
      aberrations present after LASIK. The low and high myopia spectacles groups had
      average amounts of spherical and irregular aberrations. CONCLUSIONS: Neither
      surgical techniques nor contact lenses resulted in BCVA or best corrected
      contrast sensitivity that surpassed the values measured in the best corrected
      spectacles groups. The Artisan claw lens performed better than LASIK in UCVA,
      predictability, and best corrected contrast sensitivity.

PMID- 14670417
TI  - Spherical aberration after laser in situ keratomileusis and photorefractive
      keratectomy. Clinical results and theoretical models of etiology.
AB  - PURPOSE: To assess changes in corneal asphericity after laser refractive surgery
      and mathematically model possible causes of the changes. SETTING: Cornea and
      Laser Eye Institute, Hersh Vision Group, Teaneck, New Jersey, USA. METHODS: The
      corneal topography (EyeSys 2000) of 20 eyes was measured before and after laser
      in situ keratomileusis, laser-assisted subepithelial keratectomy, and
      photorefractive keratectomy for myopia. All preoperative and postoperative maps
      were analyzed using the CTView 4.0, a computer software program for determining
      quantitative corneal spherical aberration. To define possible mechanisms of
      asphericity change, 2 mathematical models of corneal ablation were constructed
      and theoretical postoperative corneal asphericities were determined over a range
      of corrections from -12.0 to +6.0 diopters. Model 1 assumes homogeneous beam
      fluence over the ablation zone, and model 2 accounts for a theoretical ablation
      rate drop off peripherally as a result of the angle of incidence of the laser
      beam on the cornea. Postoperative clinical corneal spherical aberration was
      compared to the theoretically predicted asphericity values. RESULTS: After
      excimer laser procedures, all corneas had positive asphericity within the
      ablation zone, generally changing from a prolate to an oblate optical contour.
      The mean asphericity (Q) was -0.17 +/- 0.14 (SD) preoperatively and +0.92 +/-
      0.70 postoperatively. The mean change in spherical aberration was +1.09 +/- 0.67
      of positive asphericity; the range of asphericity change was +0.40 to +2.73 in
      the direction of a more oblate corneal profile. A trend toward greater change in
      asphericity and more oblateness was observed among eyes receiving higher
      correction. A mathematical model taking into account theoretical beam fluence
      changes across the ablation zone was highly predictive of the actual
      postoperative asphericity measurements. CONCLUSIONS: The cornea within the
      ablation zone becomes more oblate after laser refractive surgery. A mathematical
      model of the change in asphericity, which accounts for the angle of incidence of
      the laser beam across the ablation area, predicted this change in spherical
      aberration. If the model is correct, possible changes in laser algorithms,
      delivering more ablation to the peripheral optical zone, may better retain the
      native corneal prolate conformation. Moreover, wavefront-guided ablations may
      have to consider the effects of fluence variability across the optical zone to
      fully correct spherical as well as other aberrations.

PMID- 14670418
TI  - Laser-assisted subepithelial keratectomy and photorefractive keratectomy for the
      correction of hyperopia. Results of a 2-year follow-up.
AB  - PURPOSE: To evaluate and compare the efficacy, safety, predictability, and
      stability of laser-assisted subepithelial keratectomy (LASEK) and photorefractive
      keratectomy (PRK) for low to moderate hyperopia with a 2-year follow-up. SETTING:
      Department of Ophthalmology, Masaryk University Hospital, Brno, Czech Republic.
      METHODS: This prospective comparative single-surgeon study included 216 eyes of
      108 patients with hyperopia who received PRK in 1 eye and LASEK in the
      contralateral eye. The mean patient age was 38.3 years (range 25 to 58 years).
      The mean preoperative spherical equivalent (SE) cycloplegic refraction was +3.67
      diopters (D) +/- 1.15 (SD) (range +2.00 to +5.00 D), and astigmatism was less
      than 1.00 D. In each patient, PRK was performed in 1 eye (Group A) and LASEK was
      performed in the other eye (Group B) using the Nidek EC-5000 excimer laser.
      Postoperative uncorrected visual acuity (UCVA), best corrected visual acuity,
      contrast sensitivity, manifest and cycloplegic refractions, refractive stability
      and predictability, postoperative pain, and corneal haze were examined and
      statistically analyzed. A P value less than 0.05 was considered significant.
      RESULTS: At 1 week, the UCVA was 20/40 or better in 58% of PRK eyes and 85% of
      LASEK eyes (P =.037); at 2 years, it was 20/40 or better in 81% and 91%,
      respectively (P =.076). At 2 years, the UCVA for near was N8 or better in 73% of
      PRK eyes and 89% of LASEK eyes (P =.064). No patient lost 2 or more lines of
      Snellen visual acuity. The safety index was 1.03 in PRK eyes and 1.08 in LASEK
      eyes. Refractive stability was achieved at 6 months in LASEK eyes and at 12
      months in PRK eyes. The mean SE cycloplegic refraction decreased from +3.58 D
      (PRK eyes) and +3.76 D (LASEK eyes) at baseline to +0.74 D and +0.32 D,
      respectively, at 2 years; in 57% and 78% of eyes, respectively, the refraction
      was within +/-0.50 D of the targeted refraction. Peripheral corneal haze scores
      at 3 to 9 months and pain scores at 1 to 3 days were significantly lower in the
      LASEK group than in the PRK group. CONCLUSIONS: Laser-assisted subepithelial
      keratectomy for hyperopia up to +5.00 D provided good visual and refractive
      results. It significantly reduced postoperative pain, grade of peripheral ring
      shaped corneal haze, and regression of hyperopia. Hyperopic LASEK provided
      quicker visual recovery and achieved better efficacy, predictability, and
      refractive stability than hyperopic PRK.

PMID- 14670419
TI  - Anterior chamber depth in relation to refractive status measured with the Orbscan
      II Topography System.
AB  - PURPOSE: To evaluate the anterior chamber depth (ACD) according to refractive
      status, assess the reliability of repeated ACD measurements using the Orbscan II
      Topography System (Bausch and Lomb), compare Orbscan II and IOLMaster (Carl Zeiss
      Meditec AG) ACD measurements, and investigate the correlation between refraction,
      axial length (AL), and ACD. SETTING: Department of Ophthalmology, Ruprecht-Karls
      University of Heidelberg, Heidelberg, Germany. METHODS: In this clinical study,
      60 patients with a mean age of 43.8 years +/- 18.74 (SD) were assigned to 1 of 3
      groups of 20 patients each according to refraction: emmetropia group; hyperopia
      group (mean +4.84 +/- 1.60 diopters [D]); myopia group (mean -9.64 +/- 3.79 D).
      Using the Orbscan II system, 3 consecutive ACD measurements (apex and 3.0 mm
      zone) were performed. The IOLMaster was used to measure ACD and AL. RESULTS: The
      mean ACD (from epithelium) with the Orbscan II and IOLMaster, respectively, was
      3.61 +/- 0.24 mm and 3.61 +/- 0.24 mm in the emmetropia group, 3.03 +/- 0.21 mm
      and 3.06 +/- 0.24 mm in the hyperopia group, and 3.72 +/- 0.26 mm and 3.73 +/-
      0.23 mm in the myopia group. The standard deviation of the repeated Orbscan II
      measurements increased from 13 to 15 microm from the apex to the 3.0 mm zone. The
      difference between the apex and 3.0 mm zone of the cornea in all groups ranged
      from 0.1 to 0.12 mm. The mean AL was 23.52 +/- 0.82 mm in the emmetropia group,
      22.14 +/- 0.64 mm in the hyperopia group, and 27.44 +/- 1.67 mm in the myopia
      group. There was a significant correlation between the spherical equivalent and
      AL (r = 0.94). CONCLUSIONS: Significantly lower ACD values were found in the
      hyperopia group than in the other 2 groups. There was no difference in ACD
      between the emmetropia and myopia groups even though the AL in the myopia group
      was 4.0 mm longer. No statistical difference in ACD measurements was found
      between the Orbscan II and IOLMaster.

PMID- 14670420
TI  - Determining postoperative anterior chamber depth.
AB  - PURPOSE: To compare measured and calculated postoperative anterior chamber depths
      (ACDs). SETTING: Department of Ophthalmology and Institute of Medical Physics,
      University of Vienna, Vienna, Austria, and Department of Ophthalmology,
      University of Mainz, Mainz, Germany. METHODS: The postoperative ACD was measured
      in 189 pseudophakic eyes using a laboratory prototype of partial coherence
      interferometry (PCI). In 6 intraocular lens (IOL) groups, the mean ACD was
      calculated by ray tracing based on the best-known A-constants of the SRK
      formulas. In addition, for each IOL type, each measured ACD was compared with a
      value calculated using the individual spherical equivalent of the postoperative
      refraction. RESULTS: The measured and the calculated ACD values were close and
      did not show systematic differences. The ACD values obtained in the study,
      however, differed significantly from the values published by the IOL
      manufacturers. A comparison of the PCI-assessed ACDs and the calculated values
      using the postoperative refraction showed more scattered results for the
      refraction-based data, which was probably the result of higher measurement errors
      with the autorefractometer than with PCI. CONCLUSIONS: High-precision
      interferometry measurements and ray-tracing calculations confirmed each other.
      The resulting mean ACD values should be used instead of the manufacturers'
      values. The refractive outcome of cataract surgery can be improved by combining
      preoperative high-precision PCI biometry and numerical ray tracing for IOL power
      calculations.

PMID- 14670421
TI  - Capsule measuring ring to predict capsular bag diameter and follow its course
      after foldable intraocular lens implantation.
AB  - PURPOSE: To evaluate the extent of capsular bag shrinkage after cataract surgery
      with intraocular lens (IOL) implantation and develop a regression formula to
      predict postoperative capsular bag size. SETTING: Eye Hospital, Johannes
      Gutenberg-University, Mainz, Germany. METHODS: The axial length (AL), anterior
      chamber depth, and corneal radius in 58 eyes were measured preoperatively.
      Cataract surgery was by phacoemulsification followed by implantation of a 3
      piece, acrylic, posterior chamber IOL. The capsular bag diameter and anterior
      capsulorhexis were measured intraoperatively and 1 day and 1, 3, and 6 months
      postoperatively using a Koch capsule measuring ring (HumanOptics). RESULTS: The
      mean capsular bag size was 10.53 mm intraoperatively, 10.31 mm at 1 day, 9.62 mm
      at 1 month, 9.07 mm at 3 months, and 9.01 mm at 6 months. The mean capsular bag
      shrinkage over the entire postoperative period was 14.8% (P<.001). Of the
      parameters studied, only AL had a positive correlation with capsule shrinkage.
      The correlation was moderate but statistically significant (P =.001).
      CONCLUSIONS: A correlation was found between capsular bag shrinkage and AL. Using
      preoperative biometric data, a regression formula of moderate validity was
      determined to predict capsular bag shrinkage.

PMID- 14670422
TI  - Visual functional outcomes of cataract surgery in the United States, Canada,
      Denmark, and Spain: report of the International Cataract Surgery Outcomes Study.
AB  - PURPOSE: To compare functional outcomes after cataract surgery performed at 4
      sites in 4 countries that have been described as having significant differences
      in the organization of care and patterns of clinical practice. SETTING:
      Multicenter cohort study from the United States, Canada, Denmark, and Spain.
      METHODS: Clinical data and patient interview data were collected preoperatively
      and 4 months postoperatively. Functional outcomes were assessed by the Visual
      Function Index (VF-14), a self-reported measure of visual function. Scores on the
      VF-14 range from 0 (maximum impairment) to 100 (no impairment). RESULTS:
      Unilateral surgery was performed in 1073 patients. In this subgroup, the odds of
      achieving an optimal functional outcome (VF-14 score > or =95) were similar among
      sites after controlling for differences in case mix. Bilateral surgery was
      performed in 211 patients. A postoperative visual acuity of 0.50 or better in
      both eyes was reported in 155 patients. However, 37% of these patients reported
      visual function impairment (VF-14 score <95). CONCLUSIONS: A previously
      identified variation in treatment modalities among the 4 sites did not have a
      significant effect on the odds of achieving an optimal functional outcome. In
      addition to visual acuity measurements, the VF-14 index provides information on
      functional outcomes that is useful, especially in studies assessing the benefits
      of cataract surgery in a public health care setting.

PMID- 14670423
TI  - Early objective assessment of intraocular inflammation after phacoemulsification
      cataract surgery.
AB  - PURPOSE: To evaluate the time course of blood-aqueous barrier (BAB) disturbance
      in the early period after small-incision cataract surgery. SETTING: Department of
      Ophthalmology, Vienna University, Vienna, Austria. METHODS: In a prospective
      study, 15 eyes of 15 patients with age-related cataract had small-incision
      cataract surgery by phacoemulsification with intraocular lens implantation. Care
      was taken to minimize trauma to the uvea during surgery. Postoperative
      inflammation was assessed by measuring aqueous flare and cell count with a laser
      flare-cell meter. Postoperative measurements were performed hourly for the first
      6 hours, every 2 hours until 12 hours, every 4 hours until 40 hours, and every 8
      hours until 56 hours. RESULTS: The time course of aqueous flare and cell count
      differed significantly among patients. The peak inflammatory response in most
      cases was 1 hour after surgery, with the response decreasing thereafter. The
      pattern of the time course was classified into subgroups defined by the presence
      and size of an initial spike immediately after surgery and the intensity of the
      subsequent inflammatory reaction. A slight increase in flare and cells was seen
      in the morning hours of the first postoperative day. CONCLUSIONS: Acute BAB
      disturbance within the first 48 hours after small-incision cataract surgery
      showed high interpatient variability. However, many differences were not
      detectable 1 day after surgery.

PMID- 14670424
TI  - Cumulative probability of neodymium: YAG laser posterior capsulotomy after
      phacoemulsification.
AB  - PURPOSE: To retrospectively analyze the cumulative probability of neodymium:YAG
      (Nd:YAG) laser posterior capsulotomy after phacoemulsification and to evaluate
      the risk factors. SETTING: Ando Eye Clinic, Kanagawa, Japan. METHODS: In 3997
      eyes that had phacoemulsification with an intact continuous curvilinear
      capsulorhexis, the cumulative probability of posterior capsulotomy was computed
      by Kaplan-Meier survival analysis and risk factors were analyzed using the Cox
      proportional hazards regression model. The variables tested were sex; age; type
      of cataract; preoperative best corrected visual acuity (BCVA); presence of
      diabetes mellitus, diabetic retinopathy, or retinitis pigmentosa; type of
      intraocular lens (IOL); and the year the operation was performed. The IOLs were
      categorized as 3-piece poly(methyl methacrylate) (PMMA), 1-piece PMMA, 3-piece
      silicone, and acrylic foldable. RESULTS: The cumulative probability of
      capsulotomy after cataract surgery was 1.95%, 18.50%, and 32.70% at 1, 3, and 5
      years, respectively. Positive risk factors included a better preoperative BCVA (P
      =.0005; risk ratio [RR], 1.7; 95% confidence interval [CI], 1.3-2.5) and the
      presence of retinitis pigmentosa (P<.0001; RR, 6.6; 95% CI, 3.7-11.6). Women had
      a significantly greater probability of Nd:YAG laser posterior capsulotomy (P
      =.016; RR, 1.4; 95% CI, 1.1-1.8). The type of IOL was significantly related to
      the probability of Nd:YAG laser capsulotomy, with the foldable acrylic IOL having
      a significantly lower probability of capsulotomy. The 1-piece PMMA IOL had a
      significantly higher risk than 3-piece PMMA and 3-piece silicone IOLs.
      CONCLUSIONS: The probability of Nd:YAG laser capsulotomy was higher in women, in
      eyes with a better preoperative BCVA, and in patients with retinitis pigmentosa.
      The foldable acrylic IOL had a significantly lower probability of capsulotomy.

PMID- 14670425
TI  - Combined endoscopic erbium:YAG laser goniopuncture and cataract surgery.
AB  - PURPOSE: To study the safety and efficacy of endoscopic erbium:YAG (Er:YAG) laser
      goniopuncture combined with cataract surgery to treat glaucoma. SETTING:
      Department of Ophthalmology, Albert-Ludwigs-University Freiburg, Freiburg,
      Germany, and Institute of Applied Physics, University of Bern, Bern, Switzerland.
      METHODS: In this nonrandominized clinical trial, 20 eyes of 20 patients with
      cataract and glaucoma were treated by combined phacoemulsification and Er:YAG
      goniopuncture. The primary study endpoints were intraocular pressure (IOP),
      visual acuity, and number of antiglaucoma drugs 1 year after surgery. Two- and 3
      year postoperative data were also measured. This prospective treatment arm was
      compared to a retrospective inclusion-matched control group treated by cataract
      surgery alone. RESULTS: The mean IOP dropped by 30% (23.5 mm Hg +/- 3.9 [SD] to
      16.3 +/- 2.7 mm Hg) after 12 months in the laser-treated group (P<.0001) and by
      9% (19.8 +/- 1.3 mm Hg to 18.1 +/- 1.8 mm Hg) in the control group (P =.12).
      After 3 years, the mean IOP in the laser group was 15.0 +/- 2.0 mm Hg. The mean
      number of antiglaucoma drugs needed decreased from 1.6 +/- 0.9 to 0.5 +/- 0.8 in
      the laser group (P<.0001) and from 1.0 +/- 0.9 to 0.8 +/- 0.9 in the control
      group (P =.21). Anterior chamber hemorrhage occurred in 12 eyes after laser
      treatment and resolved within 72 hours in all but 1 patient who was on warfarin
      sodium (Coumadin) therapy. There were no cases of hypotony in either group.
      CONCLUSIONS: Endoscopic Er:YAG laser goniopuncture was a successful adjunct to
      cataract surgery in glaucoma patients. Sustained IOP reduction was achieved with
      few postoperative complications.

PMID- 14670426
TI  - Group IIA phospholipase A(2) content in tears of patients having photorefractive
      keratectomy.
AB  - PURPOSE: To study the effect of photorefractive keratectomy (PRK) on the
      concentration of group IIA phospholipase A(2) (GIIAPLA(2)) in tears. SETTING:
      Departments of Ophthalmology and Pathology, University of Turku, Turku, and
      Helsinki University Eye Hospital, Helsinki, Finland. METHODS: Tear samples were
      collected from 25 eyes of 23 patients (mean age 32.3 years +/- 8.6 [SD])
      preoperatively and 2 and 7 days after PRK. The GIIAPLA(2) concentration in the
      tears was measured by time-resolved fluoroimmunoassay. RESULTS: The GIIAPLA(2)
      concentration was significantly lower and the tear fluid flow rate significantly
      higher 2 days after PRK than preoperatively. At 7 days, the GIIAPLA(2)
      concentration and the tear fluid flow-corrected excretion of GIIAPLA(2) were
      significantly higher than preoperatively and at 2 days. The tear flow rate was
      also significantly higher than preoperatively. CONCLUSIONS: The GIIAPLA(2)
      content in tears decreased 2 days after PRK due to dilution of the GIIAPLA(2)
      content during hypersecretion of reflex tears. Photorefractive keratectomy caused
      an increase in the tear flow rate, GIIAPLA(2) concentration, and tear fluid flow
      corrected excretion of GIIAPLA(2) in tears 7 days after surgery, enhancing the
      protection of tears against bacterial infections.

PMID- 14670427
TI  - Black diaphragm intraocular lens implantation in aphakic eyes with traumatic
      aniridia and previous pars plana vitrectomy.
AB  - PURPOSE: To evaluate the efficacy of secondary black diaphragm intraocular lens
      (IOL) implantation in aphakic eyes with traumatic aniridia and previous pars
      plana vitrectomy (PPV). SETTING: Shandong Eye Institute and Hospital, Qingdao,
      China. METHODS: This retrospective study comprised 15 aphakic eyes with aniridia
      and no vitreous that had implantation of a secondary black diaphragm IOL 6 to 72
      months after PPV. The PPV was performed as a result of trauma to the posterior
      segment. Before implantation of the IOL, all patients had reduced visual acuity
      from aphakia and intolerable glare from aniridia. Eyes were aphakic as a result
      of previous extracapsular cataract extraction (1 eye), lens extrusion during
      trauma (3 eyes), or simultaneous cataract lensectomy during PPV (11 eyes).
      Significant iris defects were present, with 9 eyes being aniridic after the
      injury. The mean follow-up was 17 months (range 3 to 34 months). The
      postoperative visual acuity, intra- ocular pressure (IOP), endothelial cell
      density, IOL centration, and intraocular inflammation were monitored. RESULTS:
      All 15 eyes had improved visual acuity and marked glare reduction after IOL
      implantation. No major IOL decentration was seen. Five patients had increased IOP
      3 to 5 days after IOL implantation; 3 were known to have secondary glaucoma from
      trauma before surgery and their IOP was controlled preoperatively (< 21 mm Hg)
      with timolol 0.5% eyedrops. The other 2 patients had normal- appearing angles,
      and 1 was diagnosed with hemolytic glaucoma after IOL insertion. Postoperative
      elevated IOP was controlled by timolol eyedrops (4 eyes) or selective laser
      trabeculoplasty (1 eye). Hyphema was seen in 1 patient on the first day after IOL
      implantation, but no further bleeding was noted. Vitreous hemorrhage was seen the
      first day after IOL insertion in 2 patients. One resolved without sequelae; the
      other required vitreous washout. Retinal detachment and cystoid macular edema did
      not occur in any patient. CONCLUSIONS: Black diaphragm IOL implantation can be
      considered in eyes with coexisting aphakia and aniridia and without vitreous.
      Intraoperative IOP regulation is crucial in vitrectomized eyes to prevent
      complications such as expulsive hemorrhage. In general, visual function was
      better after IOL insertion as a result of better visual acuity and glare
      reduction. Although this IOL appears to be safe, long-term results must be
      assessed in studies with a longer follow-up and a larger study group.

PMID- 14670428
TI  - Elliptical ELSA (LASEK) instruments for the treatment of astigmatism.
AB  - PURPOSE: To investigate newly designed, elliptical ELSA (excimer laser
      subepithelial ablation) instruments for the treatment of astigmatism. SETTING:
      University Eye Clinic Regensburg, Regensburg, Germany, and the Rayne Institute,
      Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom.
      METHODS: The new ELSA instrument set consists of an elliptical microtrephine
      (11.0 mm x 8.0 mm) with a 70 microm calibrated blade and an elliptical alcohol
      cone (11.5 mm x 8.5 mm). With this instrument set, ELSA (the laser-assisted
      subepithelial keratectomy [LASEK] described by Camellin) was performed in 34
      astigmatic eyes. The cylindrical correction was between 1.00 diopters (D) and
      3.50 D and the spherical correction, between -0.75 D and -8.75 D. In all eyes,
      the follow-up was 6 months. The postoperative refractive outcome was analyzed
      using Alpins vector analysis. RESULTS: Excimer laser subepithelial ablation was
      performed without intraoperative complications in all eyes. At 6 months, the mean
      spherical correction was -0.04 D +/- 0.27 (SD) (range +0.75 to -0.75 D) and the
      mean cylindrical correction, 0.27 +/- 0.23 D (range 0 to 0.75 D). The mean index
      of success was 0.18 +/- 0.15. CONCLUSIONS: With the elliptical instruments, ELSA
      was an effective and safe surgical procedure for astigmatism.

PMID- 14670429
TI  - Long-term evaluation of hyperopic laser in situ keratomileusis.
AB  - PURPOSE: To evaluate the efficacy, safety, and predictability of hyperopic laser
      in situ keratomileusis (H-LASIK). SETTING: Departments of Ophthalmology, Hadassah
      University Hospital, Jerusalem, and Assaf Harofeh Medical Center, Zerifin,
      Israel. METHODS: This prospective noncomparative case series studied the results
      of H-LASIK in the first 92 consecutive eyes of 50 patients with up to +10.25
      diopters (D) of hyperopia. For analysis, the patients were divided into 3 groups
      based on preoperative hyperopia: low hyperopia (< +3.00 D), moderate hyperopia (>
      or = +3.00 to 6.00 D), and high hyperopia (> or = +6.00 D). RESULTS: Forty-two
      patients, 77 eyes (83.7%), were followed for at least 12 months. At 12 months,
      the mean manifest spherical equivalent was +0.33 +/- 0.65 D (93.1% of eyes within
      +/-1.0 D of the intended correction) in the low myopia group, +0.21 +/- 0.60 D
      (92.3% within +/-1.0 D of the intended correction) in the moderate hyperopia
      group, and +1.62 +/- 1.50 D (36.4% within +/-1.0 D of the intended correction) in
      the high hyperopia group. The uncorrected visual acuity (UCVA) was 20/40 or
      better in all eyes (100%), 24 eyes (92.3%), and 13 eyes (59.1%) in the low,
      moderate, and high hyperopia groups, respectively. Comparing the UCVA at the last
      examination with the best corrected visual acuity (BCVA) before surgery in all
      patients showed that 59 eyes (76.6%) were within +/-1 line and 18 eyes (23.4%)
      were within +/-2 or more lines of the preoperative BCVA. Three eyes (3.9%) in the
      high hyperopia group lost 2 or more lines of BCVA. Three eyes (3.9%) had flap-
      related complications. Eight patients (15 eyes) with a follow-up less than 12
      months did not have intraoperative or postoperative complications. CONCLUSION:
      Laser in situ keratomileusis was a safe, effective, and predictable procedure for
      hyperopia up to +6.0 D and less predictable for higher hyperopia.

PMID- 14670430
TI  - Actual and intended refraction after cataract surgery.
AB  - PURPOSE: To demonstrate an analytical method to compare the actual and intended
      refraction after cataract surgery that allows incorporation of refractive
      surgical effects. SETTING: Corneal and External Eye Disease Service, Royal
      Liverpool University Hospital, Liverpool, United Kingdom. METHODS: The actual
      postoperative refraction was compared to the intended postoperative refraction
      before and after removal of surgically induced changes in keratometry; that is,
      the keratometric surgical effect. Application of hypothesis testing is
      demonstrated using a standardized method of analyzing refractive data; that is,
      refractive data transformed into the refractive power matrix with calculation of
      the mean and variance-covariance of the data. RESULTS: The method of analysis
      demonstrated how surgically induced changes in refractive components can be
      incorporated into hypothesis testing when comparing intended and actual
      postoperative refractions. CONCLUSION: Application of the standardized method of
      analyzing refractive data allows a more accurate evaluation of methods or
      formulas used to calculate intraocular lens power in cataract surgery.

PMID- 14670431
TI  - Contact versus immersion biometry of axial length before cataract surgery.
AB  - PURPOSE: To compare the repeatability and agreement of contact and immersion
      ultrasound (US) biometry of axial length. SETTING: Prince of Wales Hospital,
      Sydney, Australia. METHODS: This prospective stratified randomized study
      comprised 36 patients with a preoperative refractive error less than 4.00
      diopters (D) sphere or 2.00 D cylinder who were recruited before cataract
      surgery. Each of 3 operators measured both eyes of 12 patients by contact and
      immersion US techniques. A repeat measurement by both techniques was performed by
      the same operator in 6 cases and by a different operator in the other 6. Repeat
      and operator effects were examined. RESULTS: The mean and standard deviation of
      the measurement sets were compared, and the differences between repeat measures
      were calculated. Axial length measurement was longer with the contact method than
      with immersion by 0.03 mm (P =.04). The repeatability of the 2 techniques was
      similar. CONCLUSIONS: When the measurement set was repeated, the precision of
      contact US biometry was comparable to that of immersion, with no clinically
      significant difference in mean axial length measurements.

PMID- 14670432
TI  - Feasibility of sleeveless bimanual phacoemulsification with the Millennium
      microsurgical system.
AB  - PURPOSE: To assess the feasibility of sleeveless bimanual phacoemulsification
      using the Millennium Microsurgical System (Bausch and Lomb Surgical) by measuring
      wound temperature during phacoemulsification. SETTING: In vitro laboratory.
      METHODS: The Millennium system was used in 6 eye-bank eyes using pulse mode and
      80-milllisecond and 160-millisecond phaco burst mode width intervals. Wound
      temperatures were measured, and the wounds were observed for thermal injury.
      RESULTS: In pulse mode and the nonoccluded state at 100% power, the maximum
      temperature was 43.8 degrees C. In the occluded state at 30% power, the maximum
      temperature was 51.7 degrees C after 70 seconds of occlusion. In phaco burst mode
      with a 160-millisecond burst-width interval, the maximum temperature was 41.4
      degrees C (nonoccluded at 100% power). At 80% power, the maximum temperature was
      53.2 degrees C within 60 seconds of full aspiration occlusion with the footpedal
      fully depressed. With an 80-millisecond burst-width interval in the nonoccluded
      and occluded states (100% power, footpedal fully depressed for 3 minutes), there
      was no significant temperature rise. The maximum temperature was 33.6 degrees C
      in the nonoccluded state and 41.8 degrees C in the occluded state. In all
      instances, the corneal wound remained clear. No wound burn or contracture was
      noted. CONCLUSIONS: The demonstrated temperature rises were under clinically
      unusual parameters. Phacoemulsification with a sleeveless needle through a small
      stab incision can be safely performed with the Millennium system using
      conventional phaco burst mode settings within certain parameters.

PMID- 14670433
TI  - Development of a repeatedly adjustable intraocular lens.
AB  - PURPOSE: To provide a variable-focus intraocular lens (IOL) that is able to
      adjust repeatedly and reversibly. SETTING: University of Missouri-Rolla, Rolla,
      and Eggleston Adjustable Lens, St. Louis, Missouri, USA. METHODS: An adjustable
      IOL based on a mechanically adjustable design has been developed. Prototypes were
      fabricated from traditional Perspex CQ poly(methyl methacrylate) (PMMA) provided
      off the shelf by a current IOL manufacturer. The prototypes have undergone proof
      of-concept testing per the requirements of National Institutes of Health grant 1
      R41 EY13482-01, with specific attention to the feasibility and safety of
      continuing development of the lens with in vivo trials. The experimental results
      presented focus on operational force measurements. RESULTS: Prototype lenses were
      produced consistently. Operational force measurements indicated that use of the
      mechanical adjustment mechanism is viable for an adjustable IOL and provides
      repeated adjustments over time. Turning forces exhibited by the prototypes were
      low enough to suggest that operation of this adjustable IOL will not damage the
      capsular bag or ciliary body of the eye, a potential concern in using this
      design. Biocompatibility and optical quality of the prototype lenses are ensured
      by use of traditional Perspex CQ PMMA. CONCLUSIONS: The mechanically adjustable
      IOL provides a feasible and promising means of confronting postoperative
      refractive errors and the changing desires of patients. The viability of this IOL
      design has been proven, and results suggest that operation of the lens is safe
      enough to pursue in vivo trials. Evaluation of the biocompatibility of the lens
      architecture as well as the ultimate goal of noninvasive adjustment using this
      model are reported in a companion article.

PMID- 14670434
TI  - Magnetically adjustable intraocular lens.
AB  - PURPOSE: To provide a noninvasive, magnetic adjustment mechanism to the
      repeatedly and reversibly adjustable, variable-focus intraocular lens (IOL).
      SETTING: University of Missouri-Rolla, Rolla, and Eggleston Adjustable Lens, St.
      Louis, Missouri, USA. METHODS: Mechanically adjustable IOLs have been fabricated
      and tested. Samarium and cobalt rare-earth magnets have been incorporated into
      the poly(methyl methacrylate) (PMMA) optic of these adjustable lenses. The
      stability of samarium and cobalt in the PMMA matrix was examined with leaching
      studies. Operational force testing of the magnetic optics with emphasis on the
      rotational forces of adjustment was done. RESULTS: Prototype optics incorporating
      rare-earth magnetic inserts were consistently produced. After 32 days in
      solution, samarium and cobalt concentration reached a maximum of 5 ppm.
      Operational force measurements indicate that successful adjustments of this lens
      can be made using external magnetic fields with rotational torques in excess of
      0.6 ounce inch produced. Actual lenses were remotely adjusted using magnetic
      fields. CONCLUSIONS: The magnetically adjustable version of this IOL is a viable
      and promising means of handling the common issues of postoperative refractive
      errors without the requirement of additional surgery. The repeatedly adjustable
      mechanism of this lens also holds promise for the developing eyes of pediatric
      patients and the changing needs of all patients.

PMID- 14670435
TI  - Penetrating keratoplasty for iatrogenic keratoconus after repeat myopic laser in
      situ keratomileusis: histologic findings and literature review.
AB  - We report a patient with a sufficiently thick cornea (593 microm) and no
      topographic signs of keratoconus preoperatively who developed iatrogenic
      keratoconus 2 months after repeat laser in situ keratomileusis (-4.00 -1.00 x 20)
      performed 5 months after the primary procedure (-10.50 -1.00 x 55). After
      penetrating keratoplasty, macrophotography showed severe multidirectional
      "macrostriae" of the stromal bed. On histologic evaluation, excessive thinning of
      the residual stromal bed to a minimum of 75 microm in the valleys and a maximum
      of 200 microm at the peaks of the macrostriae were documented. The flap thickness
      was 225 microm in the center. The thicker-than-intended flap (160 microm) is
      thought to be the cause of the severe complication of the LASIK procedure.

PMID- 14670436
TI  - Epithelial ingrowth in the flap-graft interface after microkeratome-assisted
      posterior penetrating keratoplasty.
AB  - A 79-year-old woman with pseudophakic bullous keratopathy had microkeratome
      assisted posterior keratoplasty for the treatment of clinically significant
      corneal edema. An island of epithelial ingrowth was noted in the flap-graft
      interface that was not communicating with the flap periphery. Partial lifting of
      the anterior corneal flap and removal and irrigation of the epithelial cells were
      successfully performed. A review of reports of microkeratome-assisted posterior
      penetrating keratoplasty shows epithelial ingrowth is common after this
      procedure. The presence of posterior sutures, a central location of the
      epithelial cells, communication with the periphery, and evidence of stromal
      melting should prompt immediate surgical intervention.

PMID- 14670437
TI  - Indocyanine green staining of anteriorly placed zonules.
AB  - The anatomy of the capsules and zonules varies with each patient, particularly in
      the zonule-free zone. We present a case in which indocyanine green dye
      highlighted the anterior lens capsule and centrally encroaching zonular fibers
      within a 2.0 mm zonule-free zone. We suggest technique modifications to reduce
      the risk for capsule extensions and related complications.

PMID- 14670438
TI  - Aggravation of proliferative diabetic retinopathy after laser in situ
      keratomileusis.
AB  - We describe a patient with proliferative diabetic retinopathy who had laser in
      situ keratomileusis (LASIK). Rapid progression and pronounced aggravation of
      diabetic retinopathy occurred after LASIK, resulting in severe visual loss in
      both eyes.

PMID- 14670439
TI  - Consequence of perforation during peribulbar anesthesia in an only eye.
AB  - A patient with a blind fellow eye had cataract surgery in the right eye;
      anesthesia comprised an intraocular injection of lidocaine and bupivacaine. Forty
      eight hours after surgery, visual acuity in the right eye was light perception
      (LP). Three days later, fundus examination showed inferotemporal hemorrhage,
      retinal whitening consistent with needle tracking, and a diffusely pale optic
      disc in the operated eye. Computed tomography showed an intact optic nerve in
      both eyes and high-density vitreal lesions in the right eye. Laser
      photocoagulation was applied to the retinal break. We believe that a jet stream
      of anesthetic agent may have transiently increased intraocular volume enough to
      occlude the central retinal artery. Although the retina remained attached, visual
      acuity failed to improve beyond LP.

PMID- 14670440
TI  - Oral pilocarpine for the treatment of keratoconjunctivitis sicca with central
      corneal irregularity.
AB  - A 31-year-old female physician with bilateral myopia had unilateral myopic laser
      in situ keratomileusis in the right eye. The patient was overcorrected with the
      initial treatment and had 2 subsequent hyperopic treatments, resulting in central
      corneal irregularity. During the course of treatment, the patient was diagnosed
      with Sjogren's syndrome with marked keratoconjunctivitis sicca. The patient had
      anisometropia, aniseikonia, and monocular diplopia and was unable to tolerate
      contact lenses. Oral pilocarpine (Salagen) was prescribed, which improved
      salivation, lacrimation, and keratoconjunctivitis sicca. The patient was able to
      tolerate rigid gas-permeable contact lenses to achieve 20/20 visual acuity in
      both eyes and regain binocular vision.

PMID- 14670441
TI  - Epithelial ingrowth under a laser in situ keratomileusis flap after
      phacoemulsification.
AB  - A 47-year-old man was referred to us for management of a cataract in the left
      eye. The patient had an ocular history of high myopia with anisometropia,
      amblyopia in the left eye, and stable myopic lattice degeneration in both eyes.
      The patient had successful bilateral laser in situ keratomileusis 3 years before
      and multiple retinal surgeries for treatment of a rhegmatogenous retinal
      detachment associated with a giant retinal tear in the temporal region of the
      retina with subsequent proliferative vitreoretinopathy. Phacoemulsification was
      performed uneventfully. A single interrupted 10-0 nylon suture was placed in the
      temporal clear corneal wound and removed 7 weeks postoperatively. One month
      later, slitlamp examination revealed a 1.5 mm tongue-like area of epithelial
      ingrowth under the corneal flap. The epithelial cells seemed to enter the flap
      stroma interface through the previously placed suture tract and advanced
      centrally.

PMID- 14670442
TI  - Bilateral nongranulomatous anterior uveitis associated with bimatoprost.
AB  - A 72-year-old man with long-standing bilateral glaucoma became refractory to
      levobunolol ophthalmic solution therapy after many years. Brimonidine was
      prescribed, but the patient developed a hypersensitivity several months later
      that was treated with loteprednol ophthalmic suspension. Bimatoprost was
      initiated 2 weeks later. Within an hour of the first dose of bimatoprost, the
      patient reported eye pain and photophobia that remained unresolved the following
      day. Examination revealed acute bilateral nongranulomatous anterior uveitis that
      was effectively treated with loteprednol. While observations in human and animal
      models suggest an association between certain prostaglandin-like agents and
      intraocular inflammation, this report is one of the first to suggest a link
      between bimatoprost and intraocular inflammatory reaction.

PMID- 14670443
TI  - Retained contact lens for more than 10 years in a laser in situ keratomileusis
      patient.
AB  - A 49-year-old man with blurred vision in 1 eye and myopic regression had laser in
      situ keratomileusis (LASIK) in the right eye after having 20/20 uncorrected
      visual acuity for 2 years. At the conclusion of surgery, a poly(methyl
      methacrylate) contact lens that had been retained for more than 10 years was
      discovered in the upper fornix. Although the patient remained asymptomatic,
      reports of significant complications associated with retained contact lenses are
      numerous. In addition, retained contact lenses, lid lesions, and periocular
      masses can induce refractive and topographic changes after LASIK. The retained
      contact lens may have led to compression-induced changes in corneal curvature,
      resulting in the need for uniocular enhancement 2 years after the primary LASIK
      procedure.

PMID- 14670444
TI  - Lightning strikes twice: expulsive choroidal hemorrhages twice in the same eye.

PMID- 14670445
TI  - Unexplained surface sensations with intracameral anesthesia in
      phacoemulsification.

PMID- 14670446
TI  - Cataract surgery with topical anesthesia-a mixed blessing.

PMID- 14670447
TI  - Helicobacter pylori flagellins have very low intrinsic activity to stimulate
      human gastric epithelial cells via TLR5.
AB  - Helicobacter pylori is a flagellated chronic pathogen, which colonizes the
      gastric mucus and mucosal cell surfaces. Flagella and motility are essential for
      the survival of this bacterium in the stomach environment. Flagellins of several
      bacterial species are potent activators of the human innate immune system by
      binding to TOLL-like receptor 5 (TLR5). The possible role of the two H. pylori
      flagellins FlaA and FlaB in stimulation of the innate immune system and induction
      of IL-8 release by human gastric epithelial cells was investigated in this study.
      Transcription and expression of TLR5 in three different human gastric epithelial
      cell lines was demonstrated. Salmonella enterica serovar Typhimurium FliC
      flagellin was able to activate human gastric epithelial cells. TLR5 transcription
      was modulated by H. pylori infection. However, both H. pylori flagellins appeared
      to possess no immunostimulatory potential on human gastric cells via TLR5,
      despite their extensive amino acid homology to stimulating flagellins of other
      bacterial species. The evolutionary development of such unique flagellins of low
      activating potential is proposed to be a novel mechanism of H. pylori to preserve
      the essential function of its flagella during chronic colonization of the stomach
      and to evade the deleterious host immune responses.

PMID- 14670448
TI  - Mixed infections with Porphyromonas gingivalis and Treponema denticola cause
      excessive inflammatory responses in a mouse pneumonia model compared with
      monoinfections.
AB  - Periodontopathic anaerobes such as Porphyromonas gingivalis are frequently found
      in aspiration pneumonia and lung abscesses. However, defense mechanisms and
      responses to these bacterial infections in the lung in vivo remain poorly
      understood. The coexistence of P. gingivalis with Treponema denticola has been
      found at higher levels and proportions in periodontally diseased sites. We
      hypothesized that mixed infections with P. gingivalis and T. denticola can cause
      severe respiratory disease. In the present study, inflammatory responses to mono-
      and mixed inoculations with P. gingivalis and T. denticola in the bronchoalveolar
      lavage (BAL) fluid were investigated. Acute pneumonia and lung abscesses in mice
      with the mixed infection resulted in a 40% mortality rate within 72 h, compared
      with only 10% mortality for the respective monoinfections. Pulmonary clearance of
      P. gingivalis was delayed in the mice with mixed infections with P. gingivalis
      and T. denticola. Tumor necrosis factor alpha (TNFalpha) interleukin-1beta (IL
      1beta) and interleukin-6 (IL-6) levels from BAL fluid of mice with mixed
      infections at 24 h after inoculation were significantly higher than those after
      P. gingivalis monoinfection (TNFalpha: P < 0.05, Il-1beta: P < 0.001, IL-6: P <
      0.05). The chemokine KC level from BAL fluid of mice at 48 h (P < 0.05) and 72 h
      after mixed infection was also significantly increased when compared with that
      after P. gingivalis monoinfection (P < 0.001). The present study demonstrates
      that a mixed infection of P. gingivalis with T. denticola in mouse causes a
      marked bronchopneumonia and lung abscess in the mouse model.

PMID- 14670449
TI  - Extracellular ATP induces cell death in CD4+/CD8+ double-positive thymocytes in
      mice infected with Trypanosoma cruzi.
AB  - In the acute phase of Trypanosoma cruzi infection, there is dramatic atrophy of
      the thymus. However, the pathways involved in this change have not yet been
      identified. This event is mainly characterized by a massive loss of cortical
      CD4+/CD8+ double-positive cells, but also by other structural and functional
      alterations in the organ. A number of molecules, including extracellular ATP,
      have been suggested to play a role in the selective processes that take place in
      the thymus. ATP and analogues trigger many different cellular responses in
      thymocytes and other cell types, such as the opening of plasma membrane cation
      channels and a pore that may induce cell death. Herein, we investigated the
      possible involvement of extracellular ATP in thymus atrophy induced by infection
      with T. cruzi. We observed that ATP induces an increase in plasma membrane
      permeabilization and cellular death in CD4+/CD8+ double-positive thymocytes
      collected from infected mice during the atrophy phase. No differences were
      observed prior to the atrophy phase or during the chronic phase. Our results
      indicate that P2Z/P2X7 receptors may play a central role in thymus atrophy during
      T. cruzi infection.

PMID- 14670450
TI  - Study of bronchoalveolar lavage fluid in paracoccidioidomycosis: cytopathology
      and alveolar macrophage function in response to gamma interferon; comparison with
      blood monocytes.
AB  - Patients with paracoccidioidomycosis (PCM) present marked involvement of the
      lungs during the course of the mycosis. The purpose of this work was to obtain
      bronchoalveolar lavage (BAL) fluid from these patients to study the
      cytopathology, TNF levels and the oxidative and fungicidal response of alveolar
      macrophages (AMs) to in vitro incubation with recombinant IFN-gamma. To compare
      the lung and blood compartments, these determinations were also made in plasma
      and blood monocytes (BMs) obtained from the same patients. The cytopathology of
      BAL fluid revealed a predominance of macrophages, but with the presence of
      neutrophil exudation, and rare lymphocytes and epithelioid and giant cells.
      Comparison of the oxidative status and fungicidal activity of AMs and circulating
      BMs demonstrated that both cell types are highly activated for these two
      functions when compared to control cells. However, TNF levels were higher in BAL
      fluid than in plasma. The possible mechanisms involved in the hyperresponsiveness
      of cells from PCM patients are discussed.

PMID- 14670451
TI  - DNA immunization with the ribosomal P2beta gene of Trypanosoma cruzi fails to
      induce pathogenic antibodies.
AB  - Patients with chronic Chagas' heart disease (cChHD) develop a strong IgG response
      against the C-terminal region of the Trypanosoma cruzi ribosomal P2beta protein
      (TcP2beta). These antibodies have been shown to exert an in vitro chronotropic
      effect on cardiocytes through stimulation of the beta1-adrenergic receptor (beta1
      AR). Moreover, the presence of antibodies recognizing the TcP2beta C-terminus was
      associated with cardiac alterations in mice immunized with the corresponding
      recombinant protein. Here, we demonstrate that DNA immunization could be used to
      modulate the specificity of the anti-TcP2beta humoral response in order to avoid
      the production of pathogenic antibodies. After DNA injection, we detected IgG
      antibodies that were directed only to internal epitopes of the TcP2beta molecule
      and that did not exert anti-beta1-AR functional activity, measured as an increase
      in intracellular cAMP levels of transfected COS-7 cells. Accordingly, DNA
      immunized mice did not present electrocardiographic alterations. These data
      demonstrate that anti-TcP2beta antibodies elicited by DNA immunization are
      completely different in their specificity and functional activity from those
      produced during T. cruzi infection.

PMID- 14670452
TI  - Fluctuations in haemocyte density and microbial load may be used as indicators of
      fungal pathogenicity in larvae of Galleria mellonella.
AB  - A positive correlation exists between the pathogenicity of bacteria and fungi
      when evaluated in the insect Galleria mellonella and mice. This work sought to
      determine whether fluctuations in the number of haemocytes and the proliferation
      of yeast cells in infected larvae could be used to determine the relative
      pathogenicity of a range of yeast isolates. Larvae were inoculated with 1 x 10(6)
      stationary-phase yeast cells and incubated in the dark at 30 degrees C for 48 h.
      The results indicated that larvae inoculated with the most pathogenic isolates
      (i.e. those capable of killing >80% of infected larvae) showed a significant
      reduction in haemocyte density. Larvae inoculated with isolates of low
      pathogenicity (i.e. capable of killing <20% of infected larvae) demonstrated only
      a small fluctuation in haemocyte numbers. The most pathogenic yeast isolates
      proliferated in the larvae, whereas the isolates of low pathogenicity did not.
      These results demonstrate a relationship between the ability of yeast isolates to
      kill larvae and changes in haemocyte density and yeast cell density in infected
      larvae. These end points may extend the applicability of the G. mellonella system
      for use with a wider range of microbial isolates.

PMID- 14670454
TI  - Richard Pfeiffer and Alexandre Besredka: creators of the concept of endotoxin and
      anti-endotoxin.
AB  - Richard Pfeiffer, working with Robert Koch in Berlin, intellectually and
      experimentally conceived the concept of endotoxin as a heat-stable bacterial
      poison responsible for the pathophysiological consequences of certain infectious
      diseases. Pfeiffer's definition of endotoxin included the inability to evoke
      neutralizing antibodies against this bacterial toxin. Alexandre Besredka, Ilya
      (Elie) Metchnikoff's successor at the Institut Pasteur in Paris, was the first to
      demonstrate that, in fact, antibodies could be engendered which were capable of
      suppressing the poisonous effects of endotoxin. Endotoxin and anti-endotoxin
      antibodies have since then fascinated researchers of many disciplines and
      continue to do so, particularly in the fields of diagnosis, prevention, and
      therapy of severe Gram-negative infections.

PMID- 14670453
TI  - A quasispecies approach to viral evolution in the context of an adaptive immune
      system.
AB  - A deeper understanding of the mechanisms that determine viral evolution in the
      context of an adaptive immune system is vital for the development of efficient
      strategies to defeat viral infections. The problem of describing these mechanisms
      is discussed using the concept of quasispecies. Conditions for both an optimal
      immune response and for highest viral viability are derived from theoretical
      models and are supported by empirical data.

PMID- 14670455
TI  - Structure, stability and vibrational spectrum of the hydrogen-bonded complex
      between HNO3 and H2O. Ab initio and DFT studies.
AB  - The structure, stability and vibrational spectrum of the binary complex between
      HONO2 and H2O have been investigated using ab initio calculations at SCF and MP2
      levels with different basis sets and B3LYP/6-31G(d,p) calculations. Full geometry
      optimization was made for the complex studied. It was established that the
      hydrogen-bonded H2O...HONO2 complex has a planar structure. The corrected values
      of the dissociation energy at the SCF and MP2 levels and B3LYP calculations are
      indicative of relatively strong OH...O hydrogen-bonded interaction. The changes
      in the vibrational characteristics (vibrational frequencies and infrared
      intensities) arising from the hydrogen bonding between HONO2 and H2O have been
      estimated by using the ab initio calculations at SCF and MP2 levels and B3LYP/6
      31G(d,p) calculations. It was established that the most sensitive to the
      complexation is the stretching O-H vibration from HONO2. In agreement with the
      experiment, its vibrational frequency in the complex is shifted to lower
      wavenumbers. The predicted frequency shift with the B3LYP/6-31G(d,p) calculations
      (-439 cm(-1)) is in the best agreement with the experimentally measured (-498 cm(
      1)). The intensity of this vibration increases dramatically upon hydrogen
      bonding. The ab initio calculations at the SCF level predict an increase up to
      five times; at the MP2 level up to 10 times and the B3LYP/6-31G(d,p) predicted
      increase is up to 17 times. The good agreement between the predicted values of
      the frequency shifts and those experimentally observed show that the structure of
      the hydrogen-bonded complex H2O...HONO2 is reliable.

PMID- 14670456
TI  - Structural study on polymorphism of long-chain dicarboxylic acids using oblique
      transmission method for micro FT-IR spectrometers.
AB  - Polymorphism and higher-order structures of even-number dicarboxylic acids from
      hexadecanedioic acid to eicosanedioic acid have been studied by micro-FTIR
      spectroscopy and microscopic observation. In order to obtain the three
      dimensional structural information, the oblique transmission method was
      incorporated into a micro-FTIR spectrometer equipped with a couple of Cassegrain
      lenses. The IR spectra showed that the solid states of dicarboxylic acid bore a
      marked structural similarity to those of n-saturated fatty acids. It was found
      that a solution-grown single crystal of dicarboxylic acids was an aggregate of
      lamellae whose thickness exceeded by far their molecular length. The surfaces of
      lamellae were covered with hydrocarbon segments taking a hairpin structure, and
      the linkage of hydrogen-bonded dicarboxylic acids formed a folded chain
      structure. The result of oblique transmission measurements showed that the
      stacking mode of lamellae varied depending on crystallization conditions.

PMID- 14670457
TI  - FTIR and FT Raman spectra and analysis of poly(4-methyl-1-pentene).
AB  - Poly(4-methyl-1-pentene) is the most widely used polymer in industry and medical
      products. Fourier transform infrared and Raman Spectra of poly(4-methyl-1
      pentene) have been recorded in the range of 4000-400 and 4000-100 cm(-1),
      respectively. In the present investigation a detailed assignments of the observed
      fundamental bands of poly(4-methyl-1-pentene) has been analyzed in terms of peak
      positions and relative intensities. With the hope of providing more and effective
      information on the fundamental vibrations, a normal coordinate analysis has also
      been performed on poly(4-methyl-1-pentene) by assuming Cs symmetry. The simple
      general valence force field (SGVFF) method has been employed in normal coordinate
      analysis and the potential energy distribution (PED) has been calculated for each
      fundamental vibration. The PED contribution corresponding to each of the observed
      frequencies shows the reliability and accuracy of spectral analysis. The validity
      of the SGVFF method as a practical tool for complete analysis of vibrational
      spectra, for poly(4-methyl-1-pentene) is confirmed in the present work.

PMID- 14670458
TI  - Surface enhanced Raman scattering of benzotriazole: a molecular orientational
      study.
AB  - Surface enhanced Raman scattering of benzotriazole in aqueous silver sol at pH
      approximately 9 has been investigated. The spectra of the molecule at various
      concentrations were recorded and the maximum enhancement was observed with a 10(
      5) M solution. From the comparison of the surface enhanced Raman spectra with the
      conventional Raman spectra and applying "surface selection rule", it is inferred
      that the molecular ion interacts with the silver sol via the nitrogen atoms of
      the benzotriazole ring and the molecule assumes a near "end-on" orientation.

PMID- 14670459
TI  - Synthesis, spectroscopic characterization and redox reactivity of some transition
      metal complexes with salicylaldimines bearing 2,6-di-phenylphenol.
AB  - New bidentate N-(2,6-di-phenyl-1-hydroxyphenyl) salicylaldimines bearing X=H and
      3,5-di-t-butyl substituents on the salicylaldehyde ring, L(x)H, and their
      copper(II) complexes, M(Lx)2, (M=Cu(II), Co(II), Pd(II), Ni(II) and Zn(II)) have
      been synthesized and characterized by IR, UV/vis, 1H NMR, 13C NMR, ESR
      spectroscopy, magnetic susceptibility measurements, as well as their oxidation
      with PbO(2) and reduction (for Cu(Lx)2) with PPh(3) were investigated. ESR
      studies indicate that oxidation of M(Lx)2 produces ligand-centered M(II)-phenoxyl
      radical species. The Cu(Lx)2 complexes, unlike others M(Lx)2, are readily reduced
      by PPh3 via intramolecular electron transfer from ligand to copper(II) to give
      unstable radical intermediates which are converted to another stable secondary
      radical species. The analysis of ESR spectra of Cu(Lx)(2), Co(L1)(2) and
      generated phenoxyl radicals are presented.

PMID- 14670460
TI  - Vibrational study of dialkylphosphonates: di-n-propyl- and di-i
      propylphosphonates by semiempirical and ab initio methods.
AB  - Fourier transform infrared and Fourier transform Raman spectra of n-C(3)H(7) and
      i-C(3)H(7) dialkylphosphonates have been obtained. Semiempirical AM1 and the ab
      initio orbital molecular RHF/6-31G* theories have been used to study the
      molecular geometry, and the harmonic vibrational spectra with the purpose to
      assist the experimental assignments of these compounds. An extensive discussion
      on the assignment of the C-C, C-O, P-O and P=O stretching is carried out based on
      experimental data of compounds which have the propyl and isopropyl groups, as
      well as comparing the vibrational spectra of propane. Most of the RHF/6-31G* and
      AM1 results, once applied the appropriate scaling factor, showed an excellent
      agreement with the experimental wavenumbers. A few calculated frequencies related
      to CC and CO stretching do not agree well with the experimental trends.

PMID- 14670461
TI  - Overtone spectra of aniline derivatives.
AB  - Overtone spectra of 2-ethylaniline, N-methylaniline, N-ethylaniline, N,N
      dimethylaniline and N,N-diethylaniline have been studied in 2500-15000 cm(-1)
      region. Vibrational frequency and anharmonicity constants for aryl/alkyl C-H
      stretch and N-H stretch vibrations have been determined. The effect of
      substitution of C(2)H(5) group on the ortho position in the ring and
      CH(3)/C(2)H(5) at the positions of the H-atom in NH(2) group has been studied in
      these molecules. It is noted that the aryl C-H stretching frequency and the N-H
      stretching frequency is appreciably increased due to the replacement of H in
      NH(2) group by CH(3)/C(2)H(5). These experimental observations are well supported
      by theoretical calculations for charge density on N-atom using molecular orbital
      AM(1) method.

PMID- 14670462
TI  - Vibrational frequencies and structural determination of 1,6-dicarba-closo
      hexaborane(6).
AB  - The normal mode frequencies and corresponding vibrational assignments of 1,6
      dicarba-closo-hexaborane(6) are examined theoretically using the GAUSSIAN98 set
      of quantum chemistry codes. All normal modes were successfully assigned to one of
      six types of motion predicted by a group theoretical analysis (B-B stretch, B-C
      stretch, B-H stretch, C-H stretch, B-H bend, and C-H bend) utilizing the D(4h)
      symmetry of the molecule. The vibrational modes of the naturally isotopically
      substituted (1-(10)B, 2-(10)B 3-(10)B, and 4-(10)B) forms of 1,6-dicarba-closo
      hexaborane(6) were also calculated and compared against experimental data. A
      complex pattern of frequency shifts and splittings is revealed.

PMID- 14670463
TI  - Spectral and magnetic properties of phenylazo-6-aminouracil complexes.
AB  - Complexes of Co(II), Ni(II) and Cu(II) with substituted phenylazo-6-aminouracils
      containing (-H, p-OH, p-CH(3), p-OCH(3) p-COOH) have been synthesized and
      characterized by elemental analysis, magnetic measurements and spectral
      measurements (IR, UV-Vis, ESR). Infrared spectra assigned the fundamental bands
      of the major groups, O-H, N-H, C-H, C=O, C=N, N=N, C-N and C-O (nu, delta and
      gamma modes of vibrations). The absence of nu(OH) and the appearance of nu(C=O)
      in the infrared spectra of the free ligands of 5-(p-tolyl and p-anisylazo)-6
      aminouracil, assigned the keto structure, whereas in cases of 5-(phenyl, p
      hydroxyphenyl and p-carboxyphenylazo)-6-aminouracil ligands, the data showed
      strong nu(OH) and nu(C=O) bands to assign keto-enol tautomerisms. The modes of
      interactions between the ligands and the metals were discussed, where oxygen and
      nitrogen atoms (of amino-amide groups) are involved in chelation. The azo group
      was not involved in chelation for all the prepared complexes except those of
      copper complexes derived from 5-(phenyl, p-tolyl, p-hydroxyphenyl and p
      carboxyphenylazo)-6-aminouracils. The room temperature effective magnetic moment
      values, the Nujol mull spectra and ESR proved that all the prepared complexes
      were of octahedral geometry, except the nickel complex derived from 5-(phenylazo)
      6-aminouracil and cobalt complex derived from 5-(p-carboxy-phenylazo)-6
      aminouracil were square planar.

PMID- 14670464
TI  - Photoluminescence and Raman studies of Sm3+ and Nd3+ ions in zirconia matrices:
      example of energy transfer and host-guest interactions.
AB  - Photoluminescence and Raman studies on Sm(3+)- and Nd(3+)-doped zirconia are
      reported. The Raman studies indicate that the monoclinic (m) phase dominates up
      to a 10 at.% lanthanide level, while stabilization of the cubic phase is attained
      at approximately 20 and approximately 25 at.% of Sm(3+) and Nd(3+), respectively.
      Both systems are strongly luminescent under photo-excitation. The emission
      spectrum at 77 K of the ZrO(2):Sm(3+) system consists of a broad band at 505 nm,
      that corresponds to the zirconia matrix. At room temperature the band maximum
      blue-shifts to 490 nm. Sharper bands corresponding to f-f transitions within the
      Sm(3+)ion are also exhibited in the longer wavelength region of the spectrum.
      Exclusive excitation of the zirconia matrix provides sensitized emission from the
      acceptor Sm(3+) ion. The excitation profile is dominated by a broad band at 325
      nm when monitored either at the zirconia or at one of the Sm(3+) emissions. A
      spectral overlap between the 6H(5/2)-->(4)G(7/2) absorption of the Sm(3+) ion
      with the zirconia emission leads to an efficient energy transfer process in the
      systems. Multiple facets of the spectral behavior of the Sm(3+) or Nd(3+) in the
      zirconia matrices, as well as the effects of compositions on the emission and
      Raman properties of the materials, and the role of defect centers in
      photoluminescence and the energy transfer processes are discussed.

PMID- 14670465
TI  - Influence of steric factors on exciplex energy and magnetic field effect.
AB  - With the advent of spin chemistry, magnetic field effect (MFE) on exciplex
      luminescence has emerged as an important domain of research. MFE is a diffusion
      controlled phenomenon and hence is solvent dielectric (epsilon) dependent. It
      maximizes at a particular epsilon (epsilon(max)) for a specific exciplex system.
      Various attempts have been made to explain the variation of this epsilon(max)
      from one exciplex to another. In our present work we have succeeded for the first
      time to enmark the energy of exciplex (E(ex)) as the prime factor in determining
      the epsilon(max). We have indicated a definite inverse correlation (1:1) between
      epsilon(max) and E(ex). We have also tried to correlate some parameters that are
      important in exciplex formation, e.g. Charton's steric constant (nu(c)),
      repulsive energy (R(e)) and E(ex).

PMID- 14670466
TI  - Electronic spectra, solvatochromic behavior and acid-base properties of some azo
      cinnoline compounds.
AB  - The electronic spectra of three azo cinnoline derivatives have been studied in
      pure and mixed organic solvents of different characteristics as well as the
      effect of concentration of the compounds in the different solvents. The different
      bands observed have been assigned to the proper electronic transition. The longer
      wavelength band displayed by the para nitro cinnoline derivative in
      dimethylformamide (DMF) solution is assigned to an intermolecular CT transition.
      The solvated H-bonding complexes formed between DMF and the para nitro derivative
      were investigated. DeltaG and K(f) values of these complexes have been
      determined. The acidity constants of the para nitro compound were determined from
      the spectra in aquous-methanolic solution of varying pH values. The effect of
      temperature on the longer wavelength visible band of p-NO(2) has been
      investigated.

PMID- 14670467
TI  - Fourier transform infrared and Raman spectra, vibrational assignment and density
      functional theory calculations of naphthazarin.
AB  - FT Raman and FTIR spectra of Naphthazarin (5,8-dihydroxy-1,4-naphthoquinone) and
      its deuterated analogue are recorded. Comparison between the spectra obtained by
      two techniques, a series of density functional theory (DFT) calculations and the
      spectral behavior upon deuteration were used for the assignment of the
      vibrational spectra of this compound. The calculated vibrational frequencies by
      the B3LYP, B3PW91, G96LYP, G96P86, and MPWLYP density functionals are generally
      consistent with the observed spectra. Infrared and Raman vibrational transitions
      predicted by B3LYP/6-311++G** are reported for the titled compound and its
      deuterated analogous and the assignments are discussed. All experimental and
      theoretical results support a relatively weak hydrogen bond in naphthazarin (NZ),
      compared with that in the enol form of normal beta-diketones. The observed
      nuOH/nuOD and gammaOH/gammaOD appear at about 3060/2220 and 790/560 cm(-1),
      respectively, which are consistent with the calculated hydrogen bond geometry and
      proton chemical shift results. Two bands at about 350 and 290 cm(-1) are assigned
      to the O...O stretching modes belong to A1 and B2 species, respectively.

PMID- 14670468
TI  - Synthesis, spectroscopic characterization, redox properties and catalytic
      activity of some ruthenium(II) complexes containing aromatic aldehyde and
      triphenylphosphine or triphenylarsine.
AB  - A series of new mixed ligand penta-coordinated square pyramidal ruthenium(II)
      complexes containing benzaldehyde or its substituents and triphenylphosphine or
      triphenylarsine have been synthesized and characterized. In the electronic
      spectra, three well-defined peaks in the visible region were observed and
      assigned to d-d transitions in D(4h) and low spin axially distortion from O(h)
      symmetry. The spectrochemical parameters of the complexes were calculated and
      placed the ligands in the middle of the spectrochemical series. The redox
      properties and stability of the complexes toward oxidation were related to the
      electron-withdrawing or releasing ability of the substituent in the phenyl ring
      of the benzaldehyde. The electron-withdrawing substituents stabilized Ru(2+)
      complexes, while electron-donating groups favored oxidation to Ru(3+). The
      mechanism and kinetics of the catalytic oxidation of benzyl alcohol by the
      complex [RuCl(2)(Pph(3))(C(6)H(5)CHO)(2)] in the presence of N-methylmorpholine-N
      oxide have also been studied.

PMID- 14670469
TI  - Luminescence spectroscopic studies of trimethinecyanines substituted in
      polymethine chain with nucleic acids and proteins.
AB  - The series of symmetrical beta-substituted and alpha,gamma-substituted
      trimethinecyanine dyes were studied for their absorption and fluorescent
      characteristics in unbound state and in the presence of nucleic acids and
      proteins. It was shown that beta-substituted and alpha,gamma-bridged
      trimethinecyanines containing extended heterocyclic systems or N-phenyl as well
      as N-cyclohexyl substituents demonstrate increased affinity to proteins. At the
      same time the presence of both N-phenyl and N-cyclohexyl substituents leads to
      the decrease of the dye fluorescence intensity in complexes with nucleic acids.
      For trimethinecyanines similarly to unsymmetrical monomethines the presence of N
      omega-hydroxy alkyl substituents results in the increase of fluorescence
      intensity of dye-DNA complex and the emission decrease of dye-RNA complex.

PMID- 14670470
TI  - Theoretical differential Raman scattering cross-sections of totally-symmetric
      vibrational modes of free pyridine and pyridine-metal cluster complexes.
AB  - The differential Raman scattering cross-sections of totally-symmetric vibrational
      modes for pyridine and pyridine-metal clusters have been calculated by using ab
      initio and density functional methods. The results are compared with experimental
      data and a good agreement is obtained. In particular, we can theoretically
      reproduce the significant changes in the relative Raman intensities of the nu(12)
      mode in pyridine-metal cluster complexes. We focus on two mechanisms for these
      Raman intensities changes: (1) the chemical interaction between the pyridine and
      the metal clusters; and (2) the charge transfer mechanism. For the pyridine
      silver cluster complexes, we find that due to the weak bonding, the chemical
      interaction does not influence the relative intensities of the Raman peaks of the
      nu(1) and nu(12) modes. However, in the case where the copper or the gold
      clusters are attached to pyridine, the intensity of the band of the nu(12) mode
      is weakened significantly. We also find that the charge transfer mechanism
      increases the asymmetry of the bands of the nu(1) and nu(12) modes on all three
      metals.

PMID- 14670471
TI  - EPR, magnetic and spectral studies of copper(II) and nickel(II) complexes of
      schiff base macrocyclic ligand derived from thiosemicarbazide and glyoxal.
AB  - A new macrocylic Schiff base 1,2,5,6,8,11-hexaazacyclododeca-7,12-dithione
      2,4,8,10-tetraene(H(2)L(4)) containing thiosemicarbazone moiety is readily
      prepared and characterized for the first time with fairly good yield. Macrocylic
      ligand (H(2)L(4)) is prepared from the mesocyle 6-ethoxy-4-thio-2,3,5
      triazine(H(2)L(3)) in ethanol with copper chloride acting as template using high
      dilution technique. The complexes of macrocylic ligand with a general composition
      M(H(2)L(4))X(2) [where M=Cu(II) or Ni(II); H(2)L(4)=1,2,5,6,8,11-hexaazacyclo
      dodeca-7,12-dithione-2,4,8,10-tetraene; X= Cl(-), NO(3)(-), (1)/(2)SO(4)(2-)] and
      ML(4) (where metal salt used to synthesize complex is copper acetate and nickel
      thiocyanate) have been synthesized. The complexes were characterized on the basis
      of elemental analysis, molar conductance, magnetic susceptibility, IR,
      electronic, 1H NMR, mass and EPR spectral studies. The complexes from H(2)L(4)
      show different stoichiometry ratio and with a variable grade of deprotonation in
      the ligand, depending upon the salt used and working conditions.

PMID- 14670472
TI  - In situ circular dichroic electrochemical study of bilirubin and bovine serum
      albumin complex.
AB  - The electrooxidation of bilirubin (BR) and bovine serum albumin (BSA) complexes
      was studied by in situ circular dichroism (CD) spectroelectrochemistry. The
      result showed that the mechanism of the whole electrooxidation process of this
      complex corresponded to electrochemical processes (EE mechanism) in aqueous
      solution. Some parameters of the process were obtained by double logarithm
      method, differential method and nonlinear regression method. In visible region,
      CD spectra of the two enantiomeric components of the complex and their fraction
      distribution against applied potentials were obtained by singular value
      decomposition least-square (SVDLS) method. Meanwhile, the distribution of the
      five components of secondary structure was also obtained by the same method in
      far-UV region. The peak potential gotten from EE mechanism corresponds to a
      turning point for the component transition, beyond which the whole reaction
      reaches a new equilibrium. Under applied positive potentials, the enantiomeric
      equilibrium between M and P form is broken and M form transfers to its enantiomer
      of P, while the fraction of alpha-helix increases and that improves the
      transition to P form.

PMID- 14670473
TI  - Preparation and study on the solid inclusion complex of sparfloxacin with beta
      cyclodextrin.
AB  - The interaction of sparfloxacin with beta-cyclodextrin (beta-CD) has been studied
      by several analytical techniques, including 1H-NMR, 13C-NMR, fluorescence
      spectroscopy, infrared spectroscopy, thermal analysis, and scanning electron
      microscope. In this paper, solid inclusion complex of sparfloxacin with beta-CD
      was synthesized by the coprecipitation method. In addition, the characterization
      of the inclusion complex has been proved by fluorimetry, Infrared, differential
      scanning calorimetry and 1D, 2D NMR. The experimental results confirmed the
      existence of 1:1 inclusion complex of sparfloxacin with beta-CD. The formation
      constant of complex was determined by fluorescence method and 1H-NMR. Spacial
      configuration of complex has been proposed on 2D NMR techniques.

PMID- 14670474
TI  - Study of charge transfer complexes of menadione (vitamin K3) with a series of
      anilines.
AB  - Menadione (vitamin K(3)) has been shown to form charge transfer complexes with
      N,N-dimethyl aniline, N,N-dimethyl p-toluidine and N,N-dimethyl m-toluidine in
      CCl(4) medium. The CT transition energies are well correlated with the ionisation
      potentials of the anilines. The formation constants of the complexes have been
      determined at a number of temperatures from which the enthalpies and entropies of
      formation have been obtained. The formation constants exhibit a very good linear
      free energy relationship (Hammett) at all the temperatures studied.

PMID- 14670475
TI  - NIR-FT Raman and infrared spectra and ab initio computations of glycinium
      oxalate.
AB  - The single crystals of glycinium oxalate are grown by slow evaporation technique
      and vibrational spectral analysis is carried out using NIR-FT Raman and FT-IR
      spectra. The ab initio quantum computations are also performed at HF/6-31 G(d)
      level to derive the optimized geometry, atomic charges and vibrational
      frequencies of the glycinium oxalate molecule. Vibrational analysis indicates the
      presence of peculiar intermolecular C-H...O hydrogen bonding interaction
      producing "blue shift" of C-H stretching frequency. The vibrational spectra
      confirm the existence of NH3(+) in glycinium oxalate. Hydroxyl vibrations with
      different inter and intra molecular H-bonding are analysed, supported by computed
      results.

PMID- 14670476
TI  - H-point standard addition method for simultaneous spectrophotometric
      determination of Co(II) and Ni(II) by 1-(2-pyridylazo)2-naphthol in micellar
      media.
AB  - A very simple and selective spectrophotometric method for simultaneous
      determination of Co(II) and Ni(II) by 1-(2-pyridylazo) 2-naphthol (PAN), in
      micellar media, using H-point standard addition method (HPSAM) is described. The
      ligand and its metal complexes (Co(II)-PAN and Ni(II)-PAN) were made water
      soluble by the neutral surfactant Triton X-100, and therefore, no extraction with
      organic solvents was required. Formation of both the complexes was complete
      within 10 min at pH 9 (adjusted by ammonia buffer). The linear range was 0.10
      2.00 microg ml(-1) for Co(II) and 0.05-1.50 microg ml(-1) for Ni(II). The
      relative standard deviation (R.S.D.) for the simultaneous determination of 0.50
      microg ml(-1) each of Co(II) and Ni(II) was 2.32 and 3.13%, respectively.
      Interference effects of common anions and cations were studied and the method was
      applied to simultaneous determination of Co(II) and Ni(II) in alloy samples. The
      method was compared with derivative spectrophotometric method.

PMID- 14670477
TI  - Experimental studies on the determination of the dipole moments of some different
      laser dyes.
AB  - In this paper we used the Stokes shift phenomena to determine the difference in
      the dipole moments of the excited state micro(e) and ground state micro(g) to be
      (micro(e)-micro(g)), and the polarizability alpha. In this paper, we studied six
      different laser dyes belonging to four different classes of laser dyes which are
      diolefin 2,5-Distyryl pyrazine (DSB); 1,4-Bis (-pyridyl-2-vinyl) benzene (P2VB)
      and p-Bis-(o-methylstyryl)-benzene (Bis-MSB) with (micro(e)-micro(g)) equal to
      6.40, 6.70 and 2.98 Debye, respectively; anthracene class includes 10(4
      acetoxyphenyl)-2-methyl-9-acetoxy anthracene (APMAA) with (micro(e)-micro(g))
      value of 7.25 Debye; Rhodamine B (RB) with (micro(e)-micro(g)) value of 5.33
      Debye; and Coumarin 120 (C120) with the value 3.97 Debye for (micro(e)-micro(g)).
      In addition the value of both polarizability alpha and the radius r of each
      investigated laser dye molecule are determined. Therefore, the ratio alpha/r(3)
      for each dye is calculated to be 0.93, 0.79, 0.39, 0.37, 0.67 and 0.76 for DSP,
      P2VB, Bis-MSB, APMAA, RB and C120, respectively. The values of r are 4.83, 4.83,
      4.90, 5.34, 5.75 and 4.11 A for the above consequence laser dyes. These dyes are
      studied in a large number of different solvents. The values obtained of (micro(e)
      micro(g)) for these selected dyes are positive, which means that the excited
      state is more polar than the ground state.

PMID- 14670478
TI  - Hydrogen bonding interactions between indole and benzenoid-pi-bases.
AB  - The NH-pi interactions of indole with benzene, naphthalene, phenanthrene,
      toluene, m-xylene, and mesitilene, in carbon tetrachloride solutions, have been
      studied by Fourier transform infrared spectroscopy. The experiments, carried out
      on the NH stretching band of indole, prove the formation of 1:1 complexes in
      which the NH bond of indole is engaged. The NH frequency shifts are independent
      of the number of rings in the base, but they progressively increase as the
      electron density is enhanced by methylation. The association constants increase
      with the increase of both, the number of rings and the methyl groups on the base.
      At higher base concentrations, further shifts on the free NH and associated bands
      indicate the formation of 1:2 complexes, which suggest hybride NH-pi and van der
      Waals interactions between one indole ring and two benzene acceptor molecules.

PMID- 14670479
TI  - Comparative study of vibrational spectra of Rb4LiH3(SO4)4, K4LiH3(SO4)4,
      K4LiH3(SeO4)4, Na5H3(SeO4)4.2H2O and Na2SeO4.H2SeO3.H2O crystals. Polarized
      infrared and Raman studies.
AB  - Vibrational spectra of M4LiH3(XO4)4 family, where M=K, Rb, X=S, Se together with
      Na5H3(SeO4)4.2H2O and Na2SeO4.H2SeO3.H2O crystals were compared. Similarities and
      differences are described. The spectroscopic manifestation of the presence of
      hydrogen bonds is discussed. Position of the bands corresponding to bending type
      of vibrations (in-plane and out-of plane) of hydrogen bonds is analyzed in the
      function of temperature. Small dynamic splitting of the bands due to weak
      interactions between ions is noticed.

PMID- 14670481
TI  - Study of the relationship of small variations of the molecular structure and the
      iron state in iron containing proteins by Mossbauer spectroscopy: biomedical
      approach.
AB  - This review considers the results of experimental Mossbauer studies and
      theoretical calculations of the effect of small variations of protein molecular
      structure on the iron electronic structure and stereochemistry in order to
      understand the proteins structural heterogeneity and functional variety.
      Structural changes in iron containing proteins during various diseases are also
      considered. These results show the relationship of the small structural
      variations and Mossbauer parameters of iron containing proteins and demonstrate
      the possibilities of Mossbauer spectroscopy to obtain new information at the
      molecular level in biomedical research.

PMID- 14670480
TI  - Raman anisotropic bandwidth study of C=O stretching vibration of methyl isobutyl
      ketone: role of van der Waals' volume of the interacting systems.
AB  - The bandwidth (FWHM) of the anisotropic component (Gamma(aniso)) of methyl
      isobutyl ketone (MIBK) for different concentrations of solvents varying from 10
      to 90% was measured and was plotted as a function of solvent concentrations. In
      lower solvent concentration, the graph shows a curvature with a discontinuity
      which occurs between 40 and 60% and in higher solvent concentration, the graph
      shows a straight line for most of the solvents. In order to interpret the
      complicated behaviour we have taken into accounts the van der Waals' volume
      (V(w)) of the sphere of influence in solute dissolved in all solvents.
      Considering the role of van der Waals' volume in these systems the parameter
      Gamma(omega)=ln(Gamma(aniso)/V(w)) was plotted at different solvent
      concentrations. The graph shows a straight line for the entire region. In order
      to study the influence of screening effect on the bandwidth, the capacitances of
      the liquid mixture at different solvent concentrations varying from 10 to 90%
      were measured for all the solvents. The plot of capacitance at different solvent
      concentrations for each solvent shows a discontinuity around 50% of solvent
      concentration.

PMID- 14670482
TI  - The interaction between amino acids and metal ions (I). The FT-IR spectroscopic
      study of the binding between D,L-homocysteic acid and alkali metal ions.
AB  - D,L-Homocysteic acid (DLH), an amino acid in the mammalian central nervous
      system, can excite the cerebral activities and has been proposed as an agonist of
      endogenous glutamate receptor. It contains -NH(3)(+), -COOH and -SO(3)(-) groups,
      therefore, the interactions between DLH and metal ions may be expected. In the
      present investigation, the complexes of DLH with NH4(+), Li+, Na+ and K+ at
      different pH conditions were synthesized and characterized by Fourier transform
      infrared (FT-IR) spectroscopy. It was concluded that the structures of the
      complexes prepared at pH 2.6 and 4.0 are similar to each other and the C=O groups
      are mono-dentate coordination for these complexes. However, the structures of the
      complexes synthesized at pH 13.0 change considerably from the complexes at pH 2.6
      and 4.0, which show that dissociation has occurred in aqueous solution. The four
      cations coordinate to DLH, which result in the rearrangement of the hydrogen bond
      network and the skeletal structure change of the ligand.

PMID- 14670483
TI  - Synthesis of molecularly imprinted polymer with 7-chloroethyl-theophylline
      immobilized silica gel as template and its molecular recognition function.
AB  - By reaction of 7-chloroethyl-theophylline with aminopropylsilanized silica gel we
      synthesized a 7-chloroethyl-theophylline-immobilized silica gel as template
      molecule and prepared a molecularly imprinted polymer (MIP-Si), which had special
      recognition sites to 7-chloroethyl-theophylline. A conventional molecularly
      imprinted polymer (MIP) using 7-chloroethyl-theophylline as template was also
      prepared for comparison. Binding abilities to 7-chloroethyl-theophylline and its
      structural analogs revealed that the MIP-Si shows much higher binding speed and
      much more binding capacity than the MIP does.

PMID- 14670484
TI  - Absorption and fluorescence spectroscopy of rhodamine 6G in titanium dioxide
      nanocomposites.
AB  - A comparison has been made between the spectroscopic properties of the laser dye
      rhodamine 6G (R6G) in mesostructured titanium dioxide (TiO(2)) and in ethanol.
      Steady-state excitation and emission techniques have been used to probe the dye
      matrix interactions. We show that the TiO(2)-nanocomposite studied is a good host
      for R6G, as it allows high dye concentrations, while keeping dye molecules
      isolated, and preventing aggregation. Our findings have important implications in
      the context of solid state dye-lasers and microphotonic device applications.

PMID- 14670485
TI  - Vibrational study of Li6P6O18.3H2O and ab initio calculations in P6O18 and
      P6O18.3H2O.
AB  - The infrared and polarized Raman spectra of the trigonal Li(6)P(6)O(18).3H(2)O
      crystal are reported. The results are analysed using several group theory
      approaches, in terms of internal and external modes of the highly symmetric
      P(6)O(18) cyclophosphoric ring and water molecules. Equilibrium geometries and
      vibrational spectra of P(6)O(18) units, free and in interaction with water
      molecules (P(6)O(18).3H(2)O) have been determined by ab initio calculations using
      the basis set 6-31+G(d) of Hartree Fock method. Experimental frequencies and
      polarisation conditions are remarkably consistent with ab initio calculations. A
      detailed description of the normal modes of vibration of these systems is
      presented.

PMID- 14670486
TI  - Determination of dysprosium by resonance light scattering technique in the
      presence of BPMPHD.
AB  - Dysprosium has been determined by resonance light scattering (RLS) method in the
      presence of 1,6-bi(1'-phenyl-3'-methyl-5'-pyrazolone-4'-)hexanedione (BPMPHD) at
      pH 5.5. The Dy-BPMPHD system has three characteristic peaks at 358, 399 and 450
      nm, especially the peak at 358 nm, which is proportional to the concentration of
      Dy(3+) in the range of 1.0 x 10(-10)-1.0 x 10(-5) mol l(-1). The detection limit
      (S/N=2) is 5.6 x 10(-12) mol l(-1). Synthetic samples are determined
      satisfactorily. A new sensitive method for detection of dysprosium has been
      proposed.

PMID- 14670487
TI  - Study on aggregation of palladium-porphyrins using room temperature
      phosphorescence.
AB  - This paper reported room temperature phosphorescence (RTP) behaviors of meso
      tetra-(4-sulfonatophenyl) porphyrin palladium (Pd-TSPP) and meso-tetra-(4
      trimethylaminophenyl) porphyrin palladium (Pd-TAPP) in bovine serum albumin (BSA)
      medium. It was found that Pd-TSPP self-aggregated with its increasing
      concentration and hetero-aggregated with Pd-TAPP when they were mixed together.
      The self-aggregation of Pd-TSPP resulted in the remarkably splitting of
      excitation spectra because of the strongly excitonic coupling and phosphorescence
      quenching excited by Soret band, while Q band always kept the increase in
      intensity. The hetero-aggregation was out of the ground-state interaction
      stronger than the former one owing to its electrostatic-interaction nature. It
      was also indicated that inorganic salts like KCl would be an aid to hetero
      aggregation. The equilibrium constants of both kinds of aggregation were
      estimated, namely, K(hom)=1.9 x 10(5) l/mol (homo-aggregation), and K(het)=1.06 x
      10(7) l/mol (hetero-aggregation).

PMID- 14670488
TI  - Derivatives of phosphate Schiff base transition metal complexes: synthesis,
      studies and biological activity.
AB  - We report the synthesis and structural characterization of series of tetra- and
      hexacoordinate metal chelate complexes of phosphate Schiff base ligands having
      the general composition LMX(n).H(2)O and L(2)MX(n) (L=phosphate Schiff base
      ligand; M=Ag(+), Mn(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+), or Fe(3+) and X=NO(3)(
      ), Br(-) or Cl(-)). The structure of the prepared compounds was investigated
      using elemental analysis, IR, 1H and 31P NMR, UV-vis, mass spectra, solid
      reflectance, magnetic susceptibility and conductance measurements as well as
      conductometric titration. In all the complexes studied, the ligands act as a
      chelate ligand with coordination involving the phosphate-O-atom and the
      azomethine-N-atom. IR, solid reflectance spectra and magnetic moment measurement
      are used to infer the structure and to illustrate the coordination capacity of
      ligand. IR spectra show the presence of coordinated nitrate and water molecule,
      the magnetic moments of all complexes show normal magnetic behavior and the
      electronic spectra of the metal complexes indicate a tetra- and octahedral
      structure for Mn(2+), octahedral structure of Fe(3+) and both square-planar and
      distorted octahedral structure for Cu(2+) complexes. Antimicrobial activity of
      the ligands and their complexes were tested using the disc diffusion method and
      the chosen strains include Staphylococcus aureus, Pseudomonas aeruginosa,
      Klebsiella pneumoniae, Escherichia coli, Microsporum canis, Trichophyton
      mentagrophyte and Trichophyton rubrum. Some known antibiotics are included for
      the sake of comparison and the chosen antibiotic are Amikacin, Doxycllin,
      Augmantin, Sulperazon, Unasyn, Septrin, Cefobid, Ampicillin, Nitrofurantion,
      Traivid and Erythromycin.

PMID- 14670489
TI  - Vibrational analysis of mononitro substituted benzamides, benzaldehydes and
      toluenes. Part I. Vibrational spectra, normal coordinate analysis and
      transferability of force constants of nitrobenzamides, nitrobenzaldehydes and
      nitrotoluenes.
AB  - The Raman and Fourier transform infrared (FTIR) spectra of p-, m- and o
      nitrobenzamides, p-, m- and o-nitrobenzaldehydes and p-, m- and o-nitrotoluenes
      were recorded. Raman polarisation measurements were made for the liquid samples.
      A normal coordinate analysis was carried out for both in-plane and out-of-plane
      vibrations of these molecules using 111-parameter modified valence force field.
      The force constants were refined using 316 frequencies of nine molecules in an
      overlay least-square technique. The reliability of the force constants was tested
      by making a zero-order calculation for nine related molecules. Unambiguous
      vibrational assignments of all the fundamentals were made by using the potential
      energy distributions and eigen vectors.

PMID- 14670490
TI  - Vibrational analysis of mononitro substituted benzamides, benzaldehydes and
      toluenes. Part II. Transferability of valence force constants.
AB  - A zero-order normal coordinate analysis of both the in-plane and out-of-plane
      vibrations was made for p-, m- and o-methylbenzaldehydes; 3,5-dichloro-p
      anisamide; 3,5-dibromo-p-anisamide; 4-chloro-3-nitrotoluene; 2-bromo-4
      nitrotoluene and 2-bromo-5-nitrotoluene by transferring the force constants
      obtained before hand. The observed and calculated frequencies agreed reasonably
      well demonstrating the transferability of the force field. On the basis of
      calculated potential energy distributions and eigen vectors, several assignments
      suggested by earlier workers have been revised.

PMID- 14670491
TI  - Infrared intensity in dielectric media by an electrostatic model.
AB  - A change in an infrared intensity in dielectric media is treated by an
      electrostatic model. The basic model is originally formalized for a dipolar
      liquid. The model is satisfactorily applied to the infrared intensity of the C-H
      stretching of chloroform, which changes 22 times large in the liquid state at -43
      degrees C as in the gaseous state. A change in the infrared intensity in lithium
      ammonium tartrate, where a ferroelectric phase transition takes place, is
      analyzed on the basis of a local polarization above T(c) or a spontaneous
      polarization below T(c), deducing important quantities on a phase transition. A
      difference in the infrared intensity of the C-Br stretching of 1,10-dibromodecane
      between the urea clathrate and the crystalline state is analyzed by evaluating
      electric fields due to bond moments and oscillating dipoles. These analyses
      confirm the mechanism of the change in the absolute infrared intensity, which
      originates from an electrostatic interaction with an electric field applied to a
      molecule or a functional group closely related to a normal mode.

PMID- 14670492
TI  - Thermal, vibrational and EPR studies of Cu(II) bromide bis(p-methylaniline) and
      bis(m-methylaniline) complexes.
AB  - [CuBr(2)(pMA)(2)] and [CuBr(2)(mMA)(2)] complexes (pMA: p-methylaniline, mMA: m
      methylaniline) have been prepared and characterized by elemental analyses,
      thermogravimetric analyses, magnetic moment measurements, and IR, Raman and EPR
      spectroscopic studies. Coordination effects on the vibrational spectra of the
      ligands have been investigated. The room temperature EPR spectra of the complexes
      and their simulated spectra are also discussed in detail. The vibrational and EPR
      spectral studies suggest that the coordination sphere around Cu(II) consist of a
      distorted tetragonal structure.

PMID- 14670493
TI  - Conformational stability, optimized geometries, vibrational and electronic
      spectra of methacryloyl bromide in ground and excited electronic states.
AB  - In order to understand conformational isomerism in methacryloyl bromide (MABR) in
      the ground (S(0)) and the first excited (S(1)) electronic states and to interpret
      the vibrational and electronic spectra of its conformers in the S(0) state,
      quantum mechanical calculations using Density Functional Theory (DFT) and RHF
      methods with extended basis sets 6-31G, 6-31G** and 6-311+G(d,p) have been
      conducted. In RHF calculations, electron correlation effects have been included
      at the Moller-Plesset MP2 level. It is inferred that in both the electronic
      states the molecule may exist in two isomeric forms-s-trans and s-cis; the former
      being more stable than the later by about 1.629 kcal mol(-1) in the S(0) state
      and by about 2.218 kcal mol(-1) in the S(1) state. Electronic transition tends to
      increase the s-trans/s-cis and s-cis/s-trans, rotational barriers from 7.059 kcal
      mol(-1) (2468.1 cm(-1)) and 5.428 kcal mol(-1) (1897.8 cm(-1)) in S(0) state to
      23.594 kcal mol(-1) (8249.4 cm(-1)) and 21.376 kcal mol(-1) (7473.9 cm(-1)) in
      the S(1) state. Completely optimized geometries of the two conformers in S(0)
      state reveal that while there is no significant difference in their bond lengths,
      some of the bond angles associated with COBr group are appreciably different.
      Electronic excitation tends to change both the bond lengths and bond angles.
      Based on suitably scaled DFT and RHF results obtained from the use of 6-31G** and
      6-311+G(d,p) basis sets, a complete assignment is provided to the fundamental
      vibrational bands of both the s-trans and s-cis conformers in terms of frequency,
      form and intensity of vibrations and potential distribution across the symmetry
      coordinates in the S(0) state and a comparison has been made with experimental
      assignments. A theoretical prediction of the electronic transitions in the near
      UV-region in the two conformers and their tentative assignment has been provided
      on the basis of CI level calculations using 6-31G basis set.

PMID- 14670494
TI  - Surface-enhanced Raman scattering and micro-Raman imaging of Langmuir-Blodgett
      films of rhodium phthalocyanine.
AB  - Rhodium phthalocyanine (RhPc) was synthesized and ultra thin Langmuir-Blodgett
      (LB) films of RhPc were successfully fabricated. The LB film characterization was
      carried out using both UV-vis absorption spectra and Raman scattering. The Raman
      spectroscopy was carried out using 633 and 780 nm laser lines. LB films were
      deposited onto Ag nanoparticles to achieve the surface-enhanced pre-resonance
      Raman scattering (pre-SERRS) and surface-enhanced Raman scattering (SERS) for
      both laser lines, respectively, which allowed the characterization of the RhPc
      ultra thin films. The morphology of the LB RhPc neat film is extracted from micro
      Raman imaging.

PMID- 14670495
TI  - Spectroscopic studies of the molecular interactions in n-ethylamines and 2
      nitropropane/n-ethylamine mixtures.
AB  - New experimental results are reported on molecular interactions in the n
      ethylamines and 2-nitropropane (2-NP)/n-ethylamine mixtures studied by Raman
      spectroscopy under pressure in a diamond anvil cell (0-50 GPa) and, at ambient
      pressure, by infrared spectroscopy. Modifications of the infrared spectra in 2-NP
      in presence of triethylamine (TEA) or diethylamine (DEA) have been observed at
      ambient pressure and interpreted as a specific molecular interaction. High
      pressure fluorescence in the vicinity of the liquid-solid phase transition of the
      2-NP/DEA and 2-NP/monoethylamine mixtures, is highlighted and discussed.

PMID- 14670496
TI  - Vibrational properties of the free and adsorbed acridone.
AB  - Theoretical density functional theory (DFT) calculation, ab initio and
      experimental vibrational characterization of acridone were performed. The
      computed vibrational modes agree well with the experimental values of the related
      crystal structure. Surface enhanced Raman scattering (SERS) of acridone in silver
      colloids with different surface potential values was studied. FT-SERS spectrum of
      acridone revealed different adsorption behavior of the title compound on the
      silver particles.

PMID- 14670497
TI  - Synthetic deuterated erythrite--a vibrational spectroscopic study.
AB  - A comparison of deuterated and non-deuterated erythrite has been made using a
      combination of infrared and Raman spectroscopy. Infrared spectrum shows bands at
      3442, 3358, 3194 and 3039 cm(-1). The band at 3442 cm(-1) is attributed to weakly
      hydrogen bonded water and the band at 3039 cm(-1) to strongly hydrogen bonded
      water. Deuteration results in the observation of OD bands at 2563, 2407 and 2279
      cm(-1). The ratio of these bands change with deuteration. Deuteration shows that
      the strongly hydrogen bonded water is replaced in preference to the weakly
      hydrogen bonded water. Three HOH bending modes are observed at 1686, 1633, 1572
      and DOD bending modes at 1236, 1203 and 1176 cm(-1). Deuteration causes the loss
      of intensity of the bands at 841, 710 and 561 cm(-1) and new bands are observed
      at 692, 648 and 617 cm(-1). These three bands are attributed to the water
      librational modes. Deuteration results in an additional Raman band at 809 cm(-1)
      with increasing intensity with extent of deuteration. Deuteration results in the
      shift of Raman bands to lower wavenumbers.

PMID- 14670498
TI  - NIR vibrational overtone spectra of N-methylaniline, N,N-dimethylaniline and N,N
      diethylaniline--a conformational structural analysis using local mode model.
AB  - In aniline, the lone pair electrons on the nitrogen atom in the amino group
      interact with the pi electrons of the ring and the mechanical frequency of the
      ring CH oscillator shows a red shift from that of benzene. This happens because
      of the parallel orientation of the pi electrons in the two molecules. This effect
      is observed in N-methylaniline also. But in N,N-dimethylaniline, the addition of
      two alkyl group to the amino group changes the parallel orientation of pi
      electrons of the nitrogen. This changes the electron donating nature of the amino
      substituent and as a result, a blue shift is observed in the mechanical frequency
      of the ring CH oscillator from that of benzene. The same effect is observed in
      the ring CH oscillator frequency of N,N-diethylaniline also.

PMID- 14670499
TI  - Eigenvector mapping: a method for discerning solvent effects on vibrational
      spectra.
AB  - This paper reports a density functional theory (DFT) analysis of the adenine
      spectra in a hydrogen-bonding environment. We compare the theoretical vibrational
      spectra of 26 model systems in which water has been hydrogen bonded to adenine
      with the experimental frequencies of the solid state infrared spectra (150-1700
      cm(-1)) of polycrystalline adenine and the experimental frequencies observed in
      matrix isolation spectra of adenine [J. Phys. Chem. 100 (1996) 3527]. The
      vibrational eigenvectors of adenine are compared by taking the dot product to
      determine how the normal modes of the 15-adenine atoms are affected by different
      hydrogen bonding geometries. Using the isolated adenine molecule as a reference
      permits a comparison of different calculated spectra in terms of the projections
      of various normal modes and the determination of the potential energy
      redistribution among normal modes. This method creates a map of the normal modes
      using the isolated adenine molecule as a reference. Improvement in agreement
      between the polycrystalline data and a model of adenine with four waters is most
      striking. The improvement in the fit between matrix isolation data and a model of
      adenine with a single water was not as dramatic as the fit seen for the
      polycrystalline data, but the fact that a single hydrogen-bonded water shifted
      the spectra of the model to a closer fit than that of isolated adenine is
      important. We call this method eigenvector mapping. The eigenvector mapping
      method can be used to extract the normal modes of a parent molecule from a
      solvent model system. The application of this method is important because it aids
      in the interpretation of complex molecular interactions in terms of the spectrum
      of an isolated molecule. The eigenvector mapping procedure will be shown to
      greatly improve the correspondence between the model and the experimental data.

PMID- 14670500
TI  - Search for IR spectral features of less-abundant diisopropylnaphthalenes based on
      comparison of theoretical and experimental spectra.
AB  - Experimental and theoretical B3PW91/6-31G* spectra of diisopropylnaphthalene
      (DIPN) were compared. For the 1,3- and 2,6-DIPN isomers, which were isolated as
      pure compounds, the theoretical IR spectra were scaled down and were shown to fit
      the experimental spectra very well. The same scaling factor was used for
      comparison theoretical and experimental spectra of isomers present in unresolved
      mixtures of isomers, i.e. 1,4-, 1,5-, 1,6-, 1,7-, and 2,7-DIPNs. For three
      isomers, 1,2-, 1,8-, and 2,3-DIPN, the experimental IR spectra, unknown so far,
      were predicted.

PMID- 14670501
TI  - The interaction of poly(ethylenimine) with nucleic acids and its use in
      determination of nucleic acids based on light scattering.
AB  - For the first time, poly(ethylenimine) (PEI) was used to determine nucleic acids
      with a light scattering technique using a common spectrofluorometer. The
      interaction of PEI with DNA results in greatly enhanced intensity of light
      scattering at 300 nm, which is caused by the formation of the big particles
      between DNA and PEI. Based on this, a new quantitative method for nucleic acid
      determination in aqueous solutions has been developed. Under the optimum
      conditions, the enhanced intensity of light scattering is proportional to the
      concentration of nucleic acid in the range of 0.01-10.0 microg ml(-1) for herring
      sperm DNA (hsDNA), 0.02-10.0 microg ml(-1) for calf thymus DNA (ctDNA), 0.02-20.0
      microg ml(-1) for yeast RNA (yRNA). The detection limits are 5.3, 9.9, and 13.7
      ng ml(-1), respectively. Synthetic samples were determined satisfactorily. At the
      same time, the light scattering technique has been successfully used to obtain
      the information on the effects of pH and ionic strength on the formation and the
      stability of the DNA/PEI complex, which is important in some fields such as
      genetic engineering and gene transfer. Using ethidium bromide (EB) as a
      fluorescent probe, the binding of PEI with hsDNA was studied. Both the binding
      constant of EB with DNA and the number of binding sites per nucleotide decrease
      with increasing concentration of PEI, indicating noncompetitive inhibition of EB
      binding to DNA in the presence of PEI. And the association constant of PEI to DNA
      obtained is 1.2 x 10(5) M(-1). IR-spectra show that PEI interacts with DNA
      through both the phosphate groups and the bases of DNA and the formation of
      DNA/PEI complex may cause the change of the conformation of the DNA secondary
      structure, which is also proved by UV-spectra.

PMID- 14670502
TI  - Resonance light scattering spectroscopy study of interaction between gold colloid
      and thiamazole and its analytical application.
AB  - In this paper, we used resonance light scattering (RLS) spectroscopy to study the
      interaction between thiol-containing pharmaceutical-thiamazole and gold colloid.
      At pH 5.2, the resonance light scattering spectrum of gold nanoparticles has a
      maximum peak at 555 nm and the RLS intensity is enhanced by trace amount of
      thiamazole due to the interaction between thiamazole and gold colloid. The
      binding of colloidal gold to thiamazole results in ligand-induced aggregation of
      colloidal gold, which was characterized by RLS spectrum, ultraviolet-visible (UV
      Vis) spectrum, and transmission electron microscopy (TEM). Based upon the study,
      we proposed a highly sensitive, gold colloid-based assay using RLS spectrum to
      detect pharmaceuticals for the first time. The mechanism of binding interaction
      between Au colloid and thiamazole was also discussed.

PMID- 14670504
TI  - Infrared study on solvent-solute interactions of 2-acetylthiophene in binary
      mixtures.
AB  - The infrared absorption spectra of the carbonyl stretching vibrations of 2
      acetylthiophene (AcTh) have been investigated in cyclo-hexane/alcohol mixtures
      (C6(12/C2H5OH; (6H12/n-C4H9OH; C6H12/i-C3H7OH and C6H12/t-C5H11OH). Five types of
      carbonyl stretching vibration bands for AcTh are found with the change of the
      mole fraction of the aprotic solvent C6H12 (x(C6H12)) in binary solvent mixtures.
      The dependencies of the frequencies of carbonyl stretching vibrations (nu(C=O))
      on x(C6H12) allow a distinction and assignment of all species resulting from the
      solvent-solute interactions. Linear correlations between the nu(C=O) of each
      species and x(C6H12) are found. The influence on the transformation of some
      species caused by the self association of alcohols is discussed.

PMID- 14670503
TI  - Spectroscopic studies on the interactions between a bioactive diperoxovanadate
      complex and pyridine.
AB  - Interactions between a bioactive diperoxovanadate complex K3[OV(O2)2(C2O4)].H2O
      and pyridine in solution were studied by 2D NMR diffusion ordered spectroscopy
      (DOSY) as well as 1D 1H, 13C, 14N, and 51V NMR, variable temperature 1H NMR and
      spin-lattice relaxation time. Competitive coordination between C2O(4)(2-) and
      pyridine to [OV(O2)(2)](-) were observed in solution. A new species
      [OV(O2)2(Py)](-) was formed and its NMR data were reported for the first time.
      The experimental results indicated that both of the vanadium atom in species
      [OV(O2)2(C2O4)](3-) and [OV(O2)2(Py)](-) are six coordinated in solution. The
      conclusion was further supported by the results of ESI-MS. The newly-formed
      species is stable under the condition of near physiological pH value.

PMID- 14670505
TI  - FT-Raman and FTIR spectroscopic studies of N-octadecanoyl-L-alanine amphiphiles.
AB  - FTIR spectroscopy is used to compare the difference in molecular structure
      between Langmuir-Blodgett (LB) films (transferred at the surface pressure 40 mN/m
      with the vertical method and 0 mN/m with the horizontal method) and bulk sample
      of N-Octadecanoyl-L-alanine amphiphiles. The bulk sample possesses a very similar
      microstructure (intermolecular hydrogen-bonding interaction and triclinic chain
      packing) to the well-ordered LB films. Much information on molecular structure of
      the bulk sample is obtained using FT-Raman spectroscopy, and several weak Raman
      scattering peaks are assigned.

PMID- 14670506
TI  - A scaled quantum mechanical force field for the sulfuryl halides. I. The
      symmetric halides SO2X2 (X=F, Cl, Br).
AB  - Force fields and vibrational wavenumbers were calculated for the molecules SO2X2
      (X=F, Cl, Br) using DFT techniques. The previously available experimental data
      and assignments for SO2F2 and SO2Cl2 were compared with the theoretical results
      and revised, and new low temperature infrared and Raman data were obtained for
      SO2Cl2. These data were subsequently used in the definition of scaled quantum
      mechanics force fields for such molecules. Adjusted wavenumbers were also
      predicted for the still unknown SO2Br2. A comparison is made with results
      published for the VO2X2- anions.

PMID- 14670507
TI  - Fourier transform infrared spectroscopy study on order-disorder transition in
      Langmuir-Blodgett films of 7-(2-octadecyloxycarbonylethyl)guanine before and
      after recognition to cytidine.
AB  - Order-disorder transitions of 9-monolayer Langmuir-Blodgett (LB) films of 7-(2
      octadecyloxycarbonylethyl)guanine (ODCG) before and after recognition to cytidine
      were investigated by Fourier transform infrared (FTIR) spectroscopy. The
      different order-disorder transitions suggest that molecular recognition between
      ODCG and cytidine influence these two LB films on the order-disorder process of
      alkyl tailchain. Cleavage of the multi-hydrogen bonds was also observed by the
      infrared spectroscopy at elevated temperature.

PMID- 14670508
TI  - An ultrafast time-resolved fluorescence spectroscopy system for metal ion
      complexation studies with organic ligands.
AB  - A dedicated spectrofluorimeter using ultrashort laser pulses as an excitation
      source was developed to measure the fluorescence properties of organic ligands
      for metal ion complexation with organic ligands. The laser system consists of an
      oscillator system for generation of femtosecond laser pulses, an amplifier system
      to increase the pulse energy of the generated pulses to about 2 mJ and an optical
      parametrical amplifier system to provide tunable laser pulses over a wide
      wavelength range (280 nm-10 microm). The laser pulses were applied to the sample
      and the emitted fluorescence was detected using a fast-gating intensified CCD
      camera-based spectrometer. To verify the performance of the laser, the well-known
      protonation constant [Pure Appl. Chem. 69 (1997) 329] of 2,3-dihydroxybenzoic
      acid was determined. The fluorescence lifetime of the excited species was
      determined as 375+/-32 ps in the pH range from 1.0 to 6.0, having a fluorescence
      emission maximum at 438 nm. The first protonation constant was determined from
      fluorescence data as log K(3)=3.17+/-0.05 at an ionic strength of 0.1 M and at
      294 K exploiting the Stern-Volmer mechanism. The agreement of the protonation
      constant with literature data (log K(3)=3.10+/-0.20, I=0.1 M, T=298 K [Bull. Soc.
      Jpn. 44 (1971) 3459]) demonstrates the excellent performance of our system.
      Furthermore, we determined the complex formation constant log K(1)=-3.11+/-0.16
      by measuring the fluorescence properties of the ligand for the 1:1
      uranyldihydroxobenzoate complex in the pH range from 3.0 to 4.5 at ionic strength
      of 0.1 M and at 294 K. We also determined the complex formation constant via the
      fluorescence emission of the metal ion uranium(VI). The fluorescence of the
      uranyl ion is influenced by dynamic quenching of the non-dissociated ligand and
      by static quenching due to the complex formation. After correction of these
      effects using the determined fluorescence lifetime, the complex formation
      constant was calculated to be log K(1)=-3.99+/-0.44. A 1:1 metal:ligand
      stoichiometry was determined with both measurement methods. However, the
      difference of the obtained formation constants and the derived standard
      deviations indicate a superimposition of effects with the excited-state reactions
      of the ligand.

PMID- 14670509
TI  - A theoretical and experimental study of Sb4O6: vibrational analysis, infrared,
      and Raman spectra.
AB  - The first ab initio theoretical study of tetraantimony hexoxide (Sb4O6) is
      reported. The normal mode frequencies, intensities, and the corresponding
      vibrational assignments of Sb4O6 in T(d) symmetry were calculated using the
      GAUSSIAN 98 set of quantum chemistry codes at the Hartree-Fock (HF)/CEP-121G,
      Moller-Plesset (MP2)/CEP-121G, and density functional theory (DFT)/B3LYP/CEP-121G
      levels of theory. By comparison to experimental data deduced by our laboratory
      and others, correction factors for the calculated vibrational frequencies were
      determined and compared. Normal modes were decomposed into three non-redundant
      motions (Sb-O-Sb stretch, Sb-O-Sb bend, and Sb-O-Sb wag). Percent relative errors
      found for the HF, DFT, and MP2 corrected frequencies when compared to experiment
      are 5.8, 6.1, and 5.7 cm(-1), respectively. Electron distributions for selected
      molecular orbitals are also considered.

PMID- 14670510
TI  - Photoacoustic investigations on the photostability of Coumarin 540-doped PMMA.
AB  - In this paper, we present a laser-induced photoacoustic study on the
      photostability of laser dye Coumarin 540 doped in PMMA matrix and modified by the
      incorporation of low-molecular weight additives. The dependence of photostability
      of the dye on various experimental conditions, such as nature of solvents,
      incident optical power and dye concentration, is investigated in detail. The
      activation rates for the bleaching process are calculated for different
      concentrations and they suggest the possibility of two distinct mechanisms
      responsible for photodegradation. Further, analysis of the data confirms the
      linear dependence of photodegradation on the intensity of incident radiation. The
      role of different externally influencing parameters, such as wavelength and
      modulation frequency of incident radiation, is also discussed.

PMID- 14670511
TI  - The mechanical and NIR studies on ultrafine calcium carbonate treated by four
      surface modifiers.
AB  - Calcium carbonate was surface treated by acrylic acid monomer, its polymerization
      with varied mean molecular weight and PS/PAA copolymer. Coating efficiencies for
      these four series of surface-treated calcium carbonate were investigated. They
      differ from each other in many aspects. We hypothesize that the treating
      molecules bond to and align on the particle surface in different ways before and
      after monolayer coverage was reached. NIR spectra of surface-treated samples
      studied not only reflected the amount of bonded treating agents by means of the
      value of absorbance, but also gave rich structural information of surface layer.
      This gave us a powerful means to investigate the interface of particle surface.

PMID- 14670512
TI  - Infrared and 13C MAS nuclear magnetic resonance spectroscopic study of
      acetylation of cotton.
AB  - The acetylation of commercial cotton samples with acetic anhydride without
      solvents in the presence of about 5% 4-dimethylaminopyridine (DMAP) catalyst was
      followed using Fourier transform infrared (FTIR) and 13C MAS NMR spectroscopy.
      This preliminary investigation was conducted in an effort to develop hydrophobic,
      biodegradable, cellulosic materials for subsequent application in oil spill
      cleanup. The FTIR results provide clear evidence for successful acetylation
      though the NMR results indicate that the level of acetylation is low.
      Nevertheless, the overall results indicate that cotton fibres are potential
      candidates suitable for further development via acetylation into hydrophobic
      sorbent materials for subsequent oil spill cleanup application. The results also
      indicate that de-acetylation, the reverse of the equilibrium acetylation
      reaction, occurred when the acetylation reaction was prolonged beyond 3 h.

PMID- 14670513
TI  - Resonance Rayleigh scattering study of the reaction of nucleic acids with
      thionine and its analytical application.
AB  - Resonance Rayleigh scattering (RRS) of the thionine (TH)-nucleic acids system and
      its analytical application have been studied. In pH 2.2 acidic buffer medium,
      some nucleic acids can react with TH to form TH-nucleic acids complex. This
      results in a great enhancement of RRS and the appearance of new RRS spectra. The
      RRS spectral characteristics of TH-ctDNA system, the affecting factors and the
      optimum conditions of the reaction have been investigated. The enhancement of the
      RRS signal is directly proportional to the concentration of nucleic acids in the
      range 0-10.0 microg/ml for calf thymus DNA and 0-15.0 microg/ml for yeast RNA,
      and its detection limits (3sigma) are 3.5 ng/ml for calf thymus DNA and 4.9 ng/ml
      for yeast RNA, respectively. The method shows a wide linear range and high
      sensitivity, and was applied to the determination of trace amounts of nucleic
      acid in synthetic samples and practical samples with satisfactory results. The
      bind properties for the interactions of TH with ctDNA were investigated using a
      Scatchard plot based on the measurement of the enhanced RRS data at 340 nm, and
      the binding number and intrinsic binding constant are 4.9 and 2.6 x 10(5)
      mol/dm(3), respectively.

PMID- 14670514
TI  - Low temperature FTIR spectroscopy and hydrogen bonding in cytosine polycrystals.
AB  - The FTIR spectra of both the pure NH and isotopically substituted ND (<10% and
      >90% D) polycrystalline cytosine were recorded in the range 400-4000 cm(-1) as a
      function of temperature (10-300 K). For the first time, uncoupled NH(D)
      stretching mode bands of amine and imine groups were observed in the spectra of
      isotopically diluted cytosine at low temperatures. These bands correspond to the
      three distinct H-bonds that are present in the crystal, in agreement with the
      available data obtained by structural methods. At least nine bands were observed
      below 1000 cm(-1) and, in consonance with their temperature and isotopic exchange
      behavior, were assigned to the NH proton out-of-the-plane bending modes. Six of
      these bands were found to correspond to additional "disordered" H-bonds, which
      could not be observed by structural methods. Empirical correlations of spectral
      and thermodynamic parameters enabled to estimate the contribution of the H-bonds
      to the sublimation enthalpy of the crystal, in agreement with independent
      experimental data.

PMID- 14670515
TI  - Computational investigation of the vibrational and electronic states of S2N2.
AB  - The structures and vibrational frequencies of the ground and excited states of
      S(2)N(2) have been calculated using density functional (DF) methods. Time
      dependent DF theory (TDDFT) has been used to calculate the excitation energies of
      the lowest 20 singlet-singlet transitions using a variety of methods. All
      computational methods predict a small highest occupied molecular orbital (HOMO)
      lowest unoccupied molecular orbital (LUMO) gap. There is some disagreement in the
      ordering of the b(2g) and b(3g) pi orbitals. This is reflected in the ordering of
      the B(2u) and B(3u) states from the TDDFT calculations. The excitation energies
      and oscillator strengths strongly suggest it is the transitions to these states
      that are responsible for the experimental electronic spectrum. The calculated
      geometries and vibrational frequencies for these two states show that both have
      C(2v) equilibrium structures. Modelling of the vibrational progressions and band
      shapes suggest that the ordering of the states is B(2u)<B(3u). Bond order
      calculations indicate significant S-S pi bonding in the ground state and that
      this is enhanced in the B(2u) excited state. The geometry of this state distorts
      by folding of the planar ring to increase the trans-annular S-S bonding.

PMID- 14670516
TI  - Spectroscopic and theoretical studies on nickel(II) complex of
      maleonitriledithiolate and 2,2'-bipyridine.
AB  - The complete IR spectra of the title complex Ni(mnt)(bpy)
      (mnt=maleonitriledithiolate, bpy=2,2'-bipyridine) and a new method to analyze
      vibrational spectra for such a complicated metal complex are reported in this
      paper. The molecular geometry, binding, electronic structure and spectroscopic
      property of it have been studied in detail by theoretical calculations. The
      geometry optimization from PM3 calculations give that this molecule is of a
      planar structure with the symmetry point group C(2v) and its ground state is the
      spin triplet state. The vibrational and electronic spectra were calculated by PM3
      and ZINDO/S methods, respectively. The scientific method of analyzing vibrational
      spectra is established herein by giving main fixed points and pivotal vibrational
      units. Besides the regular symbols, the new defined symbols eta and M play an
      important role in describing the vibration modes accurately and vividly.

PMID- 14670517
TI  - Introduction to 5-year followup treatment outcome studies.

PMID- 14670518
TI  - Overview of 5-year followup outcomes in the drug abuse treatment outcome studies
      (DATOS).
AB  - Followup results from the Drug Abuse Treatment Outcome Studies (DATOS) 1-year and
      5-year followups were used to describe the long-term outcomes of drug treatment
      and to further clarify the relationship between treatment duration and post
      treatment outcomes in four treatment modalities: outpatient methadone, long-term
      residential (LTR), outpatient drug free (ODF), and short-term inpatient. Methods
      replicating those used in earlier analyses of the DATOS 1-year followup of 2,966
      patients admitted to treatment in 1991-1993 and those of the Treatment Outcome
      Prospective Study patients admitted in 1979-1981 were employed. DATOS is a non
      experimental longitudinal study conducted within the natural settings of 96
      treatment programs in the U.S.A. The study followed patients during and after
      treatment at specified periods of time. Prevalence of drug use and behaviors were
      evaluated for the year prior to treatment; and the post-treatment time frames
      defined by the 1- and 5-year followups. In addition, the multivariate analytic
      technique of generalized estimating equations was used to examine the
      relationship of treatment duration and outcomes across both followups while also
      controlling for patient characteristics and pretreatment levels of behaviors. The
      5-year stratified followup sample included 1,393 of the same individuals in the 1
      year followup sample. Analyses were restricted to patients participating in both
      followups. Reductions in prevalence of cocaine use in the year after treatment
      (compared to the preadmission year) by patients were associated with longer
      treatment durations (particularly 6 months or more in LTR and ODF). In addition,
      reductions in illegal activity and increases in full-time employment were related
      to treatment stays of 6 months or longer for patients in LTR. The DATOS results
      from the 1-year and 5-year post-treatment followup combined suggest the stability
      of outcomes of substance abuse treatment. While results are generally consistent
      with the full 1-year followup, reduced sample size and bias of the sample toward
      patients with longer treatment retention may have attenuated the findings.

PMID- 14670519
TI  - Alcohol use outcomes and heavy drinking at 4-5 years among a treatment sample of
      drug misusers.
AB  - This paper investigates alcohol outcomes and heavy drinking among 418 drug
      misusers from the National Treatment Outcome Research Study who completed
      followup interviews at 1, 2, and 4-5 years. About a quarter of the sample were
      drinking heavily at intake. Alcohol consumption at followup was predicted by
      drinking prior to intake, and about a quarter of those who were classified as
      alcohol abstainers, medium-level drinkers, or heavy drinkers at intake, remained
      in the same drinking category at all assessment points. Drinking outcomes were
      not related to opioid use. Heavy drinkers at followup were more likely to be
      using non-opioid drugs. The poor drinking outcomes are a matter for concern. Drug
      misusers with concurrent alcohol problems may require special treatment
      provision. The extent of heavy drinking among drug misusers both before and after
      treatment indicates a need to develop and strengthen programs and interventions
      to tackle alcohol-related problems in this patient group.

PMID- 14670520
TI  - Predictors of drug treatment re-entry following relapse to cocaine use in DATOS.
AB  - Many drug abusers have repeated exposure to treatment, yet little is known about
      the reasons some individuals re-enter treatment following relapse to drug use.
      This paper examines the predictors of treatment re-entry among cocaine abusers
      who relapsed to cocaine use (N = 347) within 5 years following their index
      treatment episode. In-depth assessments were conducted at treatment intake in
      1991-93 and at 1 and 5 years following treatment discharge. About 44% of the
      sample returned to treatment, at an average of 2.6 years following discharge. A
      logistic regression analysis demonstrated that individuals who were African
      American, were previously married, used cocaine at least weekly after treatment
      discharge, and had more service needs at the time of index treatment were more
      likely to re-enter treatment. The findings suggest that a longer-term perspective
      on treatment utilization is needed to more fully address chronic substance abuse
      and the problems typically associated with it.

PMID- 14670521
TI  - Followup of cocaine-dependent men and women with antisocial personality disorder.
AB  - Long-term outcomes following drug treatment were examined for cocaine-dependent
      men (N = 453) and women (N = 254) with and without antisocial personality
      disorder (ASP). In-depth assessments were conducted at treatment intake in 1991
      93 and at 1 and 5 years following treatment discharge. Overall, 47.2% of the
      males and 34.3% of females were diagnosed with ASP using DSM-III-R criteria
      derived from the Diagnostic Interview Schedule. All groups reduced their cocaine,
      marijuana, and alcohol use; reduced their levels of psychological distress; and
      improved in functioning (e.g., employment, arrests, residential status). At Year
      5 ASP was associated with an increased likelihood of heavy alcohol use and
      additional substance abuse treatment among men, whereas women with ASP were more
      likely to report psychological problems and to receive mental health treatment
      and other services than either women without ASP or men with ASP. The findings
      suggest the need to address the specific treatment needs of male and female
      cocaine abusers with ASP.

PMID- 14670522
TI  - Patient and program factors in obtaining supportive services in DATOS.
AB  - This study examined patient and program factors that influenced the receipt of
      scheduled supportive services in the Drug Abuse Treatment Outcome Studies
      (DATOS). Patients (N = 2,932) in 21 long-term residential (LTR) programs, 27
      outpatient methadone treatment (OMT), and 25 outpatient drug-free programs were
      interviewed at admission and at 3 months during treatment. A hierarchical
      regression analysis was used to examine the relationship between patient-level
      and program-level factors associated with receiving supportive services in seven
      categories (medical, psychological, family, legal, educational, vocational, and
      financial). LTR patients received more services on average than outpatients
      (especially OMT), but patients overall received few services in the first 3
      months of treatment. The patient-level likelihood of receiving services was
      related to being female and to having higher problem severity at intake. At the
      program level, outpatient clientele with higher problem severity received more
      services if they entered a program whose other enrolled patients were less
      troubled on average.

PMID- 14670524
TI  - Delivering more effective treatment to adolescents: Improving the juvenile drug
      court model.
AB  - Juvenile drug courts (JDC) emerged in response to a perceived need to intervene
      more effectively in the substance abuse-delinquency cycle. The influx of drug and
      alcohol offenders, lack of other juvenile justice system interventions, and
      positive experiences with adult drug courts helped drive interest in adapting the
      drug court model for juveniles. This article: (1) provides an overview of
      substance use and the juvenile justice system; (2) describes the current status
      of JDC programs; and (3) proposes a model for planning, implementing and
      evaluating JDCs based on adolescent drug use and treatment research as well as
      current JDC models. The lack of science-based JDC models and empirically sound
      JDC evaluations has limited the effectiveness of JDCs. The proposed model is
      designed to create a new generation of JDCs that maximizes the effectiveness of
      local resources and delivers research-based interventions to youth and families
      impacted by substance abuse and delinquency.

PMID- 14670523
TI  - Recovery from opioid addiction in DATOS.
AB  - Patient attributions for their own long-term recovery were obtained in a 5-year
      followup of 432 admissions to 18 outpatient methadone treatment programs.
      Subjects were classified into two groups - recovering and non-recovering-strictly
      defined and based on both biological and self-report measures of no opioid or
      cocaine use, less than daily use of alcohol, and no arrests or illegal activity
      during the year prior to interview. The 28% who were in recovery at Year 5
      reported that they had relied primarily upon personal motivation, treatment
      experiences, religion/spirituality, family, and their job/career. Particular
      value was placed on the support from family and close friends, indicating the
      importance of stronger efforts to develop social networks for support of drug
      free functioning, especially among patients who lack these resources or need them
      strengthened. More information is available on the Internet at www.ibr.tcu.edu.

PMID- 14670525
TI  - Drug policy by popular referendum: This, too, shall pass.
AB  - In formulating policies for drug offenders, lawmakers must decide concrete
      questions about such matters as legal jurisdiction, burdens of proof, and
      reporting of progress information. Although these decisions may seem incidental
      to treatment and beyond the purview of science, they are based on empirically
      testable assumptions about the behavior of drug abusers and have a direct bearing
      on the efficacy of drug treatment interventions. Unfortunately, these assumptions
      have generally not been subjected to empirical inquiry. As a result, drug policy
      continues to be crafted by non-scientific advocates and subjected to popular vote
      by an insufficiently informed public. This article identifies several empirically
      answerable questions that underlie critical decision points in criminal statutes
      for drug offenders, reviews the available research evidence relevant to these
      questions, and encourages drug abuse researchers to conduct studies aimed
      squarely at informing these policy-relevant decisions.

PMID- 14670526
TI  - The promise of prison-based treatment for dually diagnosed inmates.
AB  - The Stay'n Out therapeutic community was created 25 years ago, the first
      rigorously evaluated prison program that demonstrated recidivism reduction. Since
      then, there has been a growing appreciation for the recidivism-reducing benefit
      of substance abuse treatment and the general understanding has been reached that
      prison treatment for substance abuse is good for the public interest. A number of
      replicated outcome studies have led to increases in treatment capacity in most
      state correctional systems, primarily utilizing the therapeutic community model.
      In contrast, efforts to introduce treatment for offenders with co-occurring
      mental illness and substance abuse disorders (COD) are only beginning. This
      article describes developments in prison substance abuse treatment and reentry
      programs and offers some guiding observations from prison substance abuse
      treatment history that could facilitate the development of COD treatment. Lessons
      learned include that: public safety (i.e., recidivism reduction) is a primary
      goal; personal accountability as a basic treatment value facilitates cooperation
      between treatment and correctional staff; self-help approaches foster more
      ambitious treatment goals than just symptom reduction; and well-run treatment
      programs often ease the burden of correctional administration.

PMID- 14670527
TI  - A note to researchers: Communicating science to policy makers and practitioners.
AB  - This paper provides commentary from a policy maker's perspective to researchers
      seeking to inform public policy and practice. It points to a number of issues
      that limit the usefulness of researchers' work. These issues are grouped into the
      two broad areas: format and forum. Format issues include the manner in which
      research reports are presented, their often equivocal nature, and their failure
      to take into account the cycles and calendars of executive or legislative policy
      makers. Forum issues involve, among other things, undertaking a systematic
      response to substance abuse, and related problems, among adult and juvenile
      offenders-so as to guide systemic action. The paper ends with some practical
      steps researchers can take to make their work more accessible, and useful, to
      policy makers and practitioners.

PMID- 14670528
TI  - Daphnicle dynamics based on kinetic theory: an analogue-modelling of swarming and
      behaviour of daphnia.
AB  - Attempts are presented of an analogue modelling of Daphnia responses to various
      influences and stimuli, as distribution of food and of predators. An aim of the
      study is to examine to what extent a statistical-mechanical approach may be
      useful as a tool in modelling of Daphnia swarms behaviour. In the modelling we
      follow a line close to test particle studies in physical sciences. A generalized
      kinetic equation of what we shall call daphnicles is derived. The modelling
      incorporates individual characteristics of daphnicles, as position, velocity,
      degree of food saturation and responses daphnicles have to outside influences.
      Each daphnicle we assume responds to some stimuli in ordered ways and to others
      in stochastic ways, and the degree or strength of reactions depends on the
      density of all daphnicles, the density of food available, the saturation level of
      daphnicles and the threat level in the environment, or background, the daphnicles
      are living on. Some fluid equations of daphnicle swarms are subsequently derived
      from the basic equation, and solutions are given of the model-equations,
      including a food distribution equation, in some particular cases that show
      peculiarities in reactions of daphnicles to food, degree of saturation and to
      threat, when these are acting alone, and in combination. The modelling results
      may be compared to results of laboratory experiments of Daphnia behaviour that
      soon will be performed.

PMID- 14670529
TI  - Indiscriminate polyandry and male parental effort.
AB  - Extrapair paternity involves cooperation between mated females and extrapair
      males. On the other hand, mated males exhibit a spectrum of anti-cuckolding
      strategies. Hence, extrapair attributes of diverse species and populations
      reported in the literature are particular solutions of evolutionary games
      involving gender-specific cuckolding/anti-cuckolding strategies. Here we use game
      theoretical methods to study the effect of male paternal effort conserving
      strategies in situations where females seek extrapair fertilizations (EPF) for
      reasons of genetic compatibility and/or in pursuit of genetic diversity for their
      offspring. In such cases, females cannot make a pre-copulatory selection of the
      optimal genetic partners, and therefore combine promiscuous copulation with the
      use of in copula and/or post-copulatory selection mechanisms to optimize the
      genetic endowment of their offspring-indiscriminate polyandry. Our results
      indicate that, when indiscriminate polygamy is constrained by the availability of
      extrapair male partners, there are three possible (parameter regime wise)
      evolutionary stable strategy solutions. (1). All females seek EPF, while all
      males restrict parental care. (2). All females seek EPF, while all males are
      unconditionally parental. (3). Females use a combination strategy where pursuit
      of EPF is mixed-on either a population, or an individual level-with genetic
      monogamy, while all males use a conditional paternal care strategy, which
      involves adjusting their parental efforts according to their certainty of
      paternity.

PMID- 14670530
TI  - Fire-diffuse-fire calcium waves in confined intracellular spaces.
AB  - The propagation of fire-diffuse-fire Ca(2+) waves through a three-dimensional
      rectangular domain is considered. The domain is infinite in extent in the
      direction of propagation but with lateral barriers to diffusion which contain
      Ca(2+) pumps. The Ca(2+) concentration profile due to the firing of a release
      site (spark) is derived analytically based on the Green's function for the
      diffusion equation on the domain. The existence, stability and speed of these
      waves is shown to be critically dependent on the dimensions of the domain and the
      Ca(2+) pump rate. It is shown that the smaller the dimensions of the region, the
      lower the Ca(2+) release flux required for wave propagation, and the higher the
      wave speed. Also it is shown that the region may support multiple Ca(2+)
      wavefronts of varying wave speed. This model is relevant to subsarcolemmal waves
      in atrial myocytes (Kockskamper et al., 2001, Biophys. J. 81, 2590-2605), and the
      results may be of importance in understanding the roles of the
      endoplasmic/sarcoplasmic reticulum, surface membranes and Ca(2+) pumps in the
      intracellular Ca(2+) dynamics of cells.

PMID- 14670531
TI  - The effects of spatial movement and group interactions on disease dynamics of
      social animals.
AB  - The effects of spatial movements of infected and susceptible individuals on
      disease dynamics is not well understood. Empirical studies on the spatial spread
      of disease and behaviour of infected individuals are few and theoretical studies
      may be useful to explore different scenarios. Hence due to lack of detail in
      empirical studies, theoretical models have become necessary tools in
      investigating the disease influence in host-pathogen systems. In this paper we
      developed and analysed a spatially explicit model of two interacting social
      groups of animals of the same species. We investigated how the movement scenarios
      of susceptible and infected individuals together with the between-group contact
      parameter affect the survival rate of susceptible individuals in each group. This
      work can easily be applied to various host-pathogen systems. We define bounds on
      the number of susceptibles which avoid infection once the disease has died out as
      a function of the initial conditions and other model parameters. For example,
      once disease has passed through the populations, a larger diffusion coefficient
      for each group can result in higher population levels when there is no between
      group interaction but in lower levels when there is between-group interaction.
      Numerical simulations are used to demonstrate these bounds and behaviours and to
      describe the different outcomes in ecological terms.

PMID- 14670532
TI  - Analysis of a predator-prey system with predator switching.
AB  - In this paper, we consider an interaction of prey and predator species where prey
      species have the ability of group defence. Thresholds, equilibria and stabilities
      are determined for the system of ordinary differential equations. Taking carrying
      capacity as a bifurcation parameter, it is shown that a Hopf bifurcation can
      occur implying that if the carrying capacity is made sufficiently large by
      enrichment of the environment, the model predicts the eventual extinction of the
      predator providing strong support for the so-called 'paradox of enrichment'.

PMID- 14670533
TI  - The type of seeder cells determines the efficiency of germinal center reactions.
AB  - During humoral immune responses some germinal centers (GCs) develop very well and
      give rise to a large number of high affinity antibody producing plasma cells.
      Other GC reactions develop poorly, somatic mutation is reduced, and the output
      production is practically absent. This led to the hypothesis that two classes of
      GCs exist, and that GCs show an all-or-none behaviour. We investigate the role of
      the seeder B cells affinity to the antigen in this context. It is shown in the
      framework of a space-time simulation of GC reactions that, indeed, the seeder
      cell affinity is a critical parameter that determines the fate of the GC
      reaction. Starting from a homogeneous distributions of seeder cell affinities in
      an ensemble of GC reactions, we demonstrate that an all-or-none behaviour of GCs
      has to be expected. Possible implications are discussed.

PMID- 14670534
TI  - Modelling the social dynamics of a sex industry: its implications for spread of
      HIV/AIDS.
AB  - A theoretical model is proposed for a community which has the structure of two
      classes (direct and indirect) of commercial sex workers (CSW), and two classes of
      sexually active male customers with different levels of sexual activity. The
      direct CSW's work in brothels while the indirect CSW's are based in commercial
      establishments such as bars, cafes, and massage parlours where sex can be bought
      on request and conducted elsewhere. Behaviour change and the resulting change of
      activity class occurs between the two classes of CSW's and two classes of males
      under the setting of the proliferation of human immunodeficiency virus
      (HIV)/acquired immunodeficiency syndrome epidemic and the subsequent intervention
      programmes. In recently years, this phenomenon has been observed in several
      countries in Asia. Given the lower levels of condom use and higher HIV prevalence
      of the indirect CSW's, ascertaining the impact of this change in the structure of
      the sex industry on the spread of HIV is the main focus of this paper. The
      complete analysis of the disease-free model is given. For the full model, local
      analysis will be performed for the case of preferred mixing without activity
      class change, as well as the case with activity class change and restricted
      mixing. The basic reproduction number for the spread of epidemic will be derived
      for each case. Results of biological significance include: (i). the change of
      behaviour by the CSW's has a more direct effect on the spread of HIV than that of
      the male customers; (ii). the basic reproduction number is obtained by
      considering all possible infection cycles of the heterosexual transmission of HIV
      which indicates the importance of understanding the sexual networking in
      heterosexual transmission of HIV; (iii). the social dynamics of the sex industry
      is not just a simple 'supply and demand' mechanism driven by the demand of the
      customers, hence highlighting the need for further understanding of the changing
      structure of the sex industry. The main points of this work will be illustrated
      with numerical examples using the HIV data of Thailand.

PMID- 14670535
TI  - A continuum model of motility in ameboid cells.
AB  - A continuum model of cell motility in ameboid cells based on a viscoelastic
      description of the cytoplasm and active stress generation controlled by
      extracellular signals is developed and analyzed. The characteristics of
      locomotion depend on the specific active stress, elastic and viscous properties
      of the cytoplasm as well as on the strength of cell-substrate interactions. A one
      dimensional version of the model is applied to describe the motion of a
      fibroblast. The force balance equation for the cell is solved together with
      reaction diffusion equations describing the dynamics of proteins essential for
      cell locomotion. The cell deformation is calculated, and the deformation patterns
      observed experimentally are reproduced by the model. The cell velocity as a
      function of cell-substrate interaction is also computed for various cell
      characteristics such as the active stress generated, the cell elasticity and the
      coupling between cell-substrate interaction and the ability of the cell to
      contract.

PMID- 14670537
TI  - Emerging technologies in uroradiologic imaging.
AB  - Advances in imaging technologies have readily been incorporated into the practice
      of urology and have led to important advances in patient care and outcomes. In
      the area of oncology, advances in radiologic imaging are improving the ability of
      the urologist to diagnose and monitor urologic malignancies. Some of these
      technologies include positron emission tomography (PET), intraoperative
      ultrasound (IUS), 3-dimensional computerized tomography (3D-CT), and magnetic
      resonance spectroscopy (MRS). We provide an overview of these four emerging
      imaging modalities and their potential applications and limitations in the
      diagnosis and management of urologic malignancy.

PMID- 14670538
TI  - Surgical management of renal cell carcinoma associated with complex inferior vena
      caval thrombi.
AB  - The operative morbidity and mortality of radical nephrectomy are considerably
      higher when the vena cava is involved by the tumor. The prognostic significance
      of vena caval extension in this setting remains controversial. We reviewed our
      experience of vena caval thrombectomy specifically addressing prognostic factors.
      We retrospectively studied 96 patients treated at our institution between 1985
      and 2001. The study population included 28 women and 68 men; (37 left- and 59
      right-sided tumors). Twenty-seven patients had metastatic disease at
      presentation. Prognostic features (age, sex, race, side of tumor, embolization,
      tumor grade, tumor confinement by renal capsule, cephalic extent of thrombus,
      nodal status, and presence of distant metastasis) were evaluated using a Cox
      proportional hazards model (univariate and multivariate). These prognostic
      features were analyzed in the group as a whole and in the subgroup of patients
      who did not have metastatic disease at presentation and did not die
      perioperatively. There were 5 perioperative deaths. Extracapsular tumor extension
      and regional node involvement were present in 64% and 17% of the patients,
      respectively. Level of tumor thrombus were as follows: level I (41%), II (29%),
      III (7%), IV (15%). Fuhrman's grade was 2 in 17%, 3 in 45%, and 4 in 30% of the
      patients. For all 96 patients, median overall survival (OS) was 35 months. Five
      year OS was 35%. The presence of distant metastasis at presentation did not
      significantly alter median OS (20 months with metastasis vs. 38 months without, P
      = 0.3), although this finding may have been confounded by selection. The presence
      of nodal metastasis was associated with decreased OS by multivariate analysis (P
      < 0.01). After exclusion of patients dying perioperatively and patients with
      metastasis at presentation, median OS and progression-free survival were 40 and
      18 months, respectively (5-year OS was 40%). In the multivariate model, none of
      the factors examined were associated with OS, but age <58 years, and the presence
      of extracapsular tumor extension were associated with an increased risk of
      recurrence. In patients with renal tumors and extension of tumor thrombus into
      the vena cava, the level of propagation of the thrombus does not predict for OS.
      Selected patients with metastatic renal cancer may benefit from aggressive
      surgical resection of the primary tumor and associated tumor thrombus.

PMID- 14670539
TI  - Correlation between p53 mutations and HPV in bilharzial bladder cancer.
AB  - Alterations of the p53 tumor suppressor gene are the most common genetic changes
      detected in human cancers as well as in papillary and invasive bladder cancer.
      Several studies have demonstrated an association between HPV infection and
      urological malignancies. In the present work, the p53 gene status was studied
      together with the frequency of HPV in 99 cases of Bilharzial bladder cancer [BBC]
      in Egypt and both were correlated to the clinicopathological features of the
      patients. SSCP and sequencing were used to screen the p53 gene for mutations at
      exons 4-10 and IHC was performed to detect protein overexpression. PCR was used
      for detection and typing of HPV-DNA in tumor samples. p53 mutations were detected
      in 33.3% of the studied cases whereas protein overexpression was detected in
      35.6% of the cases. The highest concordance rate was observed in cases harboring
      mutations at exon 4 [87.5%]. Bilharzial infestation was obvious in 72.2% of the
      cases that showed mutations. Exon 8 showed the highest rate of mutation [32%]
      followed by exons 4 and 5 [22% each]. The commonest mutational event was G:C
      transversion [15/50] especially at CpG dinucleotides. A mutational hot spot was
      detected at exon 4, codons 72-73. HPV-DNA was detected in 48.97% of the cases the
      majority of which [64.6%] were of type 16. Significant correlation was found
      between p53 mutation and the pathological stage as well as p53 overexpression and
      tumor grade. Our results demonstrate that the mutational spectrum in BBC is
      different from that of bladder cancer in Western countries in many aspects and
      suggest an etiological role of HPV in this type of neoplasm. However, both HPV
      infection and p53 gene abnormalities may contribute to Bilharzial bladder
      carcinogenesis in an independent way.

PMID- 14670540
TI  - Treatment of refractory urothelial carcinoma with alternating paclitaxel,
      methotrexate, cisplatin (TMP) and 5-fluorouracil, alpha-interferon, cisplatin
      (FAP).
AB  - We assessed the activity and safety of a biochemotherapy regimen in which courses
      of paclitaxel, methotrexate, and cisplatin were alternated with courses of 5
      fluorouracil, alpha-interferon, and cisplatin in the treatment of refractory
      urothelial carcinoma. Forty patients were enrolled in the study. In the phase I
      portion, 15 patients were treated according to an escalating dosage regimen
      designed to determine the maximum tolerated dose. A total of 30 patients received
      treatment according to the maximum tolerated dose regimen: methotrexate (30
      mg/m(2)) given iv on days 1 and 22; paclitaxel (175 mg/m(2)) given iv over 3 h on
      day 1; cisplatin (70 and 25 mg/m(2)) administered iv on days 1 and 22,
      respectively; 5-fluorouracil (400 mg/m(2)) given iv by continuous infusion daily
      for 5 days beginning on day 22; and alpha-interferon (4 mIU/m(2)) given SC daily
      for 5 days simultaneously with the 5-fluorouracil infusions. The regimen was
      repeated at 42-day intervals. The 40 treated patients had an overall response
      rate of 43%, a complete response rate of 18%, and a median survival time of 44
      weeks. Most of the toxic effects were hematologic: Grade 4 neutropenia occurred
      in 30% of patients (12 patients) and Grade 3 thrombocytopenia in 20% (8
      patients). Even though this alternating biochemotherapy regimen was active for
      patients with refractory urothelial carcinoma, its activity was not better than
      that of certain single cytotoxic agents. Furthermore, the complicated dosing
      schedule and toxic effects of the regimen precluded its routine use in the
      treatment of urothelial carcinoma.

PMID- 14670541
TI  - Histologic confirmation of lesions identified by Prostascint scan following
      definitive treatment.
AB  - The purpose of the study was to determine the accuracy of the monoclonal antibody
      (Mab) [Prostascint, Cytogen, Inc.] scan for the detection of nodal metastases
      using histologic examination of surgical lymphadenectomy specimens as the
      standard of reference. We reviewed the records of 31 patients who had undergone
      biopsy after monoclonal antibody scan. Histologic evaluation was obtained for a
      total of 31 patients and 43 pathology samples. When analyzed by surgical site,
      the sensitivity, specificity, positive predictive value, negative predictive
      value and accuracy of the Mab scan were 94%, 42%, 53%, 92% and 65%, respectively.
      When analyzed by individual patient, the same data for the Mab scan were 100%,
      33%, 62%, 100% and 68%, respectively. Current noninvasive studies are not
      sufficiently accurate to reliably determine the presence of metastatic nodal
      disease from prostate cancer. This series illustrates the importance of rigorous
      clinical evaluation of future methods that are designed to detect microscopic
      metastatic disease of any neoplasm.

PMID- 14670544
TI  - Bacillus Calmete-Guerin plus interferon-alpha2B intravesical therapy maintains an
      extended treatment plan for superficial bladder cancer with minimal toxicity.
AB  - Bacillus Calmette-Guerin (BCG) and interferon-alpha2B (IFN-alpha2B) have both
      been individually used for the intravesical treatment of superficial bladder
      cancer. We report our experience on the therapeutic efficacy and toxicity of
      combined intravesical BCG plus IFN-alpha2B for treating superficial bladder
      cancer, including patients failing previous BCG therapy. Thirty-two patients with
      superficial bladder cancer underwent 6 weekly treatments with full-, one-third,
      or one-tenth-dose of BCG plus 50 or 100 MU of IFN-alpha2B based on prior BCG
      exposure and tolerance. Patients with no evidence of disease proceeded onto
      maintenance therapy of 3 weekly treatments at 3 months followed by 2 additional
      maintenance cycles given 6 months apart. Response was assessed by
      cystoscopy/biopsy every 3 months after treatment. Before BCG plus IFN-alpha2B
      treatment, 20 patients (63%) had previously failed intravesical BCG therapy, 27
      (84%) had aggressive disease (stage T1, grade 3, or carcinoma in situ), 27 (84%)
      had recurrent disease, 14 (44%) had multifocal disease, and 6 (19%) had disease
      of over 4 years duration. At median follow-up of 22 months, 21 patients (66%)
      remain disease-free and 11 patients (34%) had disease-recurrence. Nineteen of 32
      patients (59%) were disease-free after the initial induction cycle. Six of 11
      patients 55% ultimately failing combination therapy did so at the first 3 to 4
      month evaluation. Four of 7 patients (57%) benefited from salvage re-induction
      therapy. Of the 20 patients previously treated with BCG, 12 patients (60%) remain
      disease-free. Combination BCG plus IFN-alpha2B intravesical therapy was well
      tolerated. Combination intravesical BCG plus IFN-alpha2B is an effective and
      tolerable alternative for patients with superficial bladder cancer, including
      those patients in whom intravesical BCG therapy had previously failed. Benefits
      of this combination therapy may include potentially less morbidity, improved
      clinical efficacy, and in the long term, fewer patients undergoing radical
      therapy. However, radical treatment options should be pursued for early failures
      of this combination regimen in those patients with risk factors for recurrence
      and progression.

PMID- 14670545
TI  - The utility of apical anterior horn biopsies in prostate cancer detection.
AB  - We sought to determine the utility of adding apical anterior horn biopsies to
      systematic prostate sampling regimens in detecting cancer in men with measured
      prostate volume < or =50 cc. We reviewed the biopsy data of consecutive men
      referred for an abnormal digital rectal exam or PSA elevation > or =4.0 ng/mL.
      All of these patients underwent lesion directed biopsy as well as a systematic 12
      core biopsy regimen consisting of the standard sextant, bilateral lateral mid-
      and lateral base-sites, and bilateral apical anterior horn sites. Overall cancer
      detection and unique cancer detection rates were calculated for each of the 12
      sites, stratified by race, age, PSA, and findings on digital rectal exam. In
      addition, cancer detection rates of various biopsy schemes were calculated and
      compared. There were 255 men undergoing biopsy who had calculated prostate volume
      < or =50 cc, and the prostate cancer detection rate was 47%. The overall cancer
      detection rate of apical anterior horn biopsies ranged between 29% and 56%. The
      utility of these biopsies was greatest in men with normal rectal exam and PSA <10
      ng/mL, with unique cancer detection rates of 6% and 4%, respectively. Including
      the apical anterior horn biopsies in an 8-biopsy scheme (anterior, apex, lateral
      mid, lateral base) yielded cancer detection rates greater than 91% in all
      subgroups that were not statistically different from extended 10- and 12-core
      biopsy regimens. Apical anterior horn prostate biopsies target cancers that are
      potentially in the anterior region of the prostate, a region under-sampled using
      traditional schemes. The use of these biopsies as part of an 8-core biopsy
      pattern provides high cancer detection in all groups of patients and may
      represent a new standard.

PMID- 14670546
TI  - Chromosome 18 suppresses prostate cancer metastases.
AB  - Loss of heterozygosity and allelic imbalance data has shown that there are two
      distinct regions of loss on chromosome 18q associated with the progression of
      prostate cancer (CaP). To investigate the functional significance of chromosome
      18q loci in CaP, we utilized the technique of microcell-mediated chromosome
      transfer to introduce an intact chromosome 18 into the human prostate cancer cell
      line, PC-3. Three of the resulting hybrid lines were compared to the PC-3 cells
      in vitro and in vivo. The hybrid cell lines, containing an intact copy of the
      introduced chromosome 18, exhibited a substantial reduction in anchorage
      dependent and independent growth in vitro. These hybrid cell lines also made
      smaller tumors in nude mice following subcutaneous injection compared to PC-3
      cells. Because tumor growth was not completely eliminated by introduction of
      chromosome 18, we assessed the ability of the hybrids to metastasize to bone
      after intra-cardiac inoculation in a nude mouse model. Mice inoculated with PC-3
      hybrids containing intact copies of chromosome 18 had significantly fewer bone
      metastases and dramatically improved survival compared to PC-3 cells. In
      addition, the introduction of chromosome 18 significantly reduced tumor burden in
      extraskeletal sites. This was not because of differences in growth rates because
      mice bearing hybrids were monitored for metastases over twice as long as mice
      bearing PC-3 cells. Taken together, these data suggest that chromosome 18 has a
      functional role in CaP to suppress growth and metastases. Identification of the
      responsible gene(s) may lead to molecular targets for drug discovery.

PMID- 14670547
TI  - Osteoporosis and prostate cancer.

PMID- 14670548
TI  - Osteoporosis: a rapid review of risk factors and screening methods.
AB  - Osteoporosis is a significant problem in women and it is beginning to become a
      recognized etiology of morbidity and mortality in men. However, before reviewing
      any potential therapies, it is imperative that clinicians first gain adequate
      knowledge on the risk factors for osteoporosis and fractures, and the various
      screening methods that are utilized in clinical practice. For example, advancing
      age, hormonal status, lifestyle, and overall diet are just a few of the potential
      risk factors. The majority of the risk factors in men seem to parallel those that
      have already been well known in women. Heel ultrasound (HUS), dual-energy X-ray
      absorptiometry (DEXA), and quantitative computerized tomography (QCT) are the
      most popular and effective methods utilized for osteoporosis screening. All of
      these imaging tests contain an inherent number of advantages and limitations.
      This brief review serves as a simplistic but important primer to a condition that
      is increasing in prevalence in a diverse area of medical fields.

PMID- 14670549
TI  - Risk factors for male osteoporosis.
AB  - Hypogonadism from long-term androgen deprivation therapy (ADT), either by
      bilateral orchiectomy or administration of gonadotropin-releasing hormone (GnRH)
      agonists, causes significant and accelerated bone loss that may increase the risk
      of bone fractures in men with prostate cancer. Recent reports, as well as new
      data from our institution, have shown a high prevalence of pre-existing
      osteopenia and osteoporosis in men with prostate cancer before receiving ADT, and
      this is of great concern because of the risk of further bone loss during ADT.
      Data from these studies suggest the urgent need for clinical guidelines for
      screening, prevention, and treatment of these cases. This article reviews the
      prevalence and risk factors associated with osteoporosis in men and addresses
      risk factors in men with prostate cancer not receiving ADT. Considerations for
      the patient selection and timing of bone densitometry will also be discussed.

PMID- 14670550
TI  - The potential benefits of dietary and/or supplemental calcium and vitamin D.
AB  - Osteoporosis is a significant problem in women and men. In addition, as
      osteoporosis has garnered more attention there should be more attention than ever
      placed on the potential benefits of calcium and vitamin D. Clinicians need to
      inform patients that there are numerous healthy dietary sources of calcium and
      vitamin D. Calcium and vitamin D supplements seem to act synergistically to
      reduce fracture risk in men and women; therefore, they need to be taken together
      to impact fracture risk. In addition, almost every randomized trial of an
      effective osteoporosis drug therapy has utilized calcium and vitamin D to enhance
      the efficacy of the drug itself. Several forms of calcium supplements are
      commercially available today and clinicians need to understand the similarities
      and differences between them. Calcium and vitamin D in moderation also have a
      good safety profile and may actually have benefits far beyond osteoporosis
      therapy. For example, calcium may increase high-density lipoprotein (HDL),
      prevent colon polyps, reduce blood pressure, reduce kidney stone recurrence, and
      may promote weight loss. Vitamin D may reduce the risk of some cancers, provide
      an enhanced response to some chemotherapeutic agents, prevent type I diabetes,
      and may reduce tooth loss along with calcium. Clinicians need to encourage
      individuals to receive the recommended daily allowance of these two agents
      because they seem to have an impact on numerous health conditions besides
      osteoporosis.

PMID- 14670551
TI  - Bone loss and the evolving role of bisphosphonate therapy in prostate cancer.
AB  - Androgen deprivation therapy (ADT) can result in significant loss of bone mineral
      density (BMD) but to date, there are no prospective studies that document the
      true severity of bone loss and resulting fracture rates. In the general
      population, however, the incidence of low BMD is increasing in elderly men. Men
      suffer more morbidity and mortality from fractures associated with low BMD than
      women. Problems of underdiagnosis and undertreatment in men can be addressed with
      enhanced awareness of the risk factors for bone loss in men and the available
      treatment options. Guidelines for diagnosis of low BMD in women can probably be
      applied to men. Treatment options have not been studied as extensively in men.
      For men treated with ADT for prostate cancer, however, use of intravenous
      zoledronic acid at the initiation of ADT has been shown to prevent and even
      reverse bone loss. Although the routine use of bisphosphonates to prevent bone
      loss is not yet recommended, zoledronic acid is a logical choice of therapy in
      men who have low BMD at baseline or who develop bone loss during the course of
      therapy. In addition to its effects on BMD, zoledronic acid has also been shown
      to decrease skeletal morbidity in men with metastatic hormone-refractory prostate
      cancer. Whether zoledronic acid or other bisphosphonates might actually prevent
      or delay the development of bone metastases remains to be studied in randomized
      clinical trials.

PMID- 14670552
TI  - Development of weekly high-dose calcitriol based therapy for prostate cancer.
AB  - Calcitriol, the principal biologically active ligand of the Vitamin D receptor
      (VDR), has been shown to inhibit cancer cell proliferation in in vitro and in
      vivo models of prostate cancer and a wide range of other neoplasms. In addition,
      calcitriol's activity appears to be additive, and in some experimental systems,
      synergistic with dexamethasone and several cytotoxic chemotherapy agents. While
      effects on progression through the cell cycle, induction of apoptosis, inhibition
      of angiogenesis, and reduction in tumor invasiveness have been demonstrated, the
      exact mechanisms of VDR-mediated antineoplastic activity remain incompletely
      understood. Antineoplastic activity of calcitriol requires substantially
      supraphysiologic concentrations of this compound. Dose escalation of calcitriol
      administered daily was severely limited by predictable hypercalcemia and/or
      hypercalcuria. This limitation has been overcome with intermittent dosing of
      calcitriol. At Oregon Health & Science University, weekly oral administration of
      calcitriol allowed the attainment of peak serum calcitriol concentrations well
      above 1 nM, a concentration that inhibits prostate cancer proliferation by more
      than 50% in vitro. Weekly high-dose calcitriol was then combined with weekly
      docetaxel in a Phase II clinical trial carried out in men with metastatic
      androgen-independent prostate cancer. Treatment resulted in PSA response (defined
      as a confirmed 50% reduction) in 81% of patients. This level of activity, as well
      as the median time to progression of 11.4 months and median survival of 19.5
      months, compared favorably to results with docetaxel alone and led to the
      development of a recently initiated randomized trial of docetaxel with calcitriol
      or placebo in the same patient population.

PMID- 14670569
TI  - A cognitive characterization of dyscalculia in Turner syndrome.
AB  - Current theories of number processing postulate that the human abilities for
      arithmetic are based on cerebral circuits that are partially laid down under
      genetic control and later modified by schooling and education. This view predicts
      the existence of genetic diseases that interfere specifically with components of
      the number system. Here, we investigate whether Turner syndrome (TS) corresponds
      to this definition. TS is a genetic disorder which affects one woman in 2500 and
      is characterized by partial or complete absence of one X chromosome. In addition
      to well-characterized physical and hormonal dysfunction, TS patients exhibit
      cognitive deficits including dyscalculia. We tested 12 women with Turner syndrome
      and 13 control subjects on a cognitive battery including arithmetical tests
      (addition, subtraction, multiplication, division) as well as tests of the
      understanding of numerosity and quantity (cognitive estimation, estimation,
      comparison, bisection, subitizing/counting). Impairments were observed in
      cognitive estimation, subitizing, and calculation. We examine whether these
      deficits can be attributed to a single source, and discuss the possible
      implications of hormonal and genetic factors in the neuropsychological profile of
      TS patients.

PMID- 14670568
TI  - The relationships between morphological and phonological errors in aphasic
      speech: data from a word repetition task.
AB  - Current theories of single-word processing predict that in some cases brain
      damage should selectively impair morphological processes, resulting in the
      selective occurrence of morphological errors. However, such a selective pattern
      of errors has never been documented, and the available case studies report the
      systematic association of morphological and phonological (segmental) errors in
      the same subject. The number of relevant case reports is very small, however. To
      better understand the relationship between morphological and phonological
      processes, we analyzed the repetition performance of 26 subjects who produced
      morphological errors in a screening battery for aphasia. Although the results
      confirm that subjects who make morphological errors also invariably make
      phonological errors, the probabilities of the two types of errors are not
      (quantitatively) correlated. Furthermore, the relationship between morphological
      and phonological errors was asymmetrical: although all subjects who produced
      morphological errors also produced phonological errors, some aphasics who
      produced phonological errors did not also produce morphological errors. The one
      way relationship between morphological and phonological errors could result
      either from the anatomical proximity of the structures involved in morphological
      and phonological processes, or from the functional inseparability of the two
      processes. The fact that phonological errors can occur either in isolation or in
      association with morphological errors could be attributed to the functional
      heterogeneity of phonological errors, and to the separability of the neural
      substrates involved in processing various aspects of phonological information.

PMID- 14670570
TI  - A metanalysis of impaired and spared naming for different categories of knowledge
      in patients with a visuo-verbal disconnection.
AB  - The study of the neuroanatomical correlates of category-specific semantic
      disorders has strongly supported the 'sensory/motor model of semantic knowledge,'
      which assumes that the cortical areas that have critically contributed to the
      development of various categories are also implicated in their semantic
      representation. However, if the anatomo-clinical correlates are consistent with
      the model, less clearcut results have been obtained by functional neuroimaging
      experiments. In the present metanalysis, I addressed the question from a
      different viewpoint, shifting attention from the anatomical lesion in patients
      with category-specific semantic disorders to the pattern of naming impairment
      shown by patients suffering from a disconnection between visual areas and lexical
      output mechanisms. According to the model, living entities should be particularly
      impaired, since their semantic representations are mainly based upon visual
      perceptual attributes. On the contrary, actions and body parts (and to a lesser
      extent artefacts) should be relatively spared, as their semantic representations
      are mainly based upon motor, somato-sensory or functional attributes. These
      predictions were checked by reviewing the categorical pattern of naming
      impairment shown by patients with a visuo-verbal disconnection and a category
      specific naming impairment published in the last 20 years. The pattern of
      impaired and spared categories observed in these patients was consistent with the
      hypothesis, since: (1) 'actions' and 'body parts' were systematically spared in
      comparison to all the other categories; (2) 'artefacts' were relatively spared
      with respect to the 'living categories'; and (3) within the biological
      categories, 'plants' were usually more impaired than animals.

PMID- 14670571
TI  - Hemispheric specialisation for imitation of hand-head positions and finger
      configurations: a controlled study in patients with complete callosotomy.
AB  - Several studies of patients with unilateral brain damage and a patient with
      spontaneous callosal disconnection [Journal of Neurology, Neurosurgery, and
      Psychiatry 61 (1996) 176; Neuropsychologia 37 (1999) 559; Neuropsychologia 39
      (2001) 1432] suggest that the imitation of positions of the hand relative to the
      head is a strongly lateralised left hemispheric function. In contrast, the
      imitation of finger configurations draws on resources of both hemispheres with a
      predominance of the right hemisphere. While these findings suggest a specific
      pattern of imitation impairment in split-brain patients, thus far, no imitation
      deficits have been reported in split-brain patients. Three patients with complete
      callosotomy and two control groups, four patients with partial callosotomy and 10
      healthy subjects, imitated hand-head positions and finger configurations with non
      lateralised and tachistoscopic stimulus presentation. In addition, the influence
      of visual control on the imitation performance was examined. One split-brain
      patient showed the predicted dissociation as she had severe right hemispheric
      deficit in imitating hand-head positions, while finger configuration imitation
      was preserved. The other two split-brain patients had no impairment in hand-head
      position imitation. Withdrawal of visual control significantly deteriorated
      imitation of finger configurations in the split-brain group, but not in the
      controls, demonstrating that the split-brain patients relied heavily on visual
      control as a compensatory strategy indicating an imitation deficit in the
      separate hemispheres. The findings question the previously held belief that in
      split-brain patients both hemispheres are perfectly capable of imitating gestures
      and that imitation is not dependent on hemispherically specialised functions.

PMID- 14670572
TI  - The effects of saliency and task difficulty on visual search performance in
      ageing and Alzheimer's disease.
AB  - We asked whether the poor performance on visual search tasks typical of patients
      with Alzheimer's disease (AD) is the result of a selective deficit in the ability
      to shift attention from item to item, or the consequence of an inefficient
      processing of each item within the search set. We attempted to manipulate the
      ease of attention shifting and item processing in a visual search task by
      manipulating target salience and task difficulty, respectively. Significant
      effects of both target saliency and task difficulty for both AD patients and age
      matched controls were obtained, with the AD group displaying greater effects of
      both of these manipulations than the controls. This interaction remained even
      when the reaction time data were log-transformed to account for the overall
      slower reaction times of the AD group. We conclude that inefficiency in visual
      search tasks in AD probably represents the product of both attention shifting and
      target processing factors.

PMID- 14670573
TI  - Gradients of detection in neglect: comparison of peripersonal and extrapersonal
      space.
AB  - Previous studies of target-cancellation performance in visuospatial neglect
      patients have reported lateral (left-right) and radial (near-far) gradients of
      attentional ability. The purpose of the present study was to replicate the
      reported attentional gradients in peripersonal space (within arms reach) and to
      examine whether lateral gradients of detection also appear in extrapersonal space
      (beyond arms reach), using equivalent tasks with no manual requirement. The
      relationship between radial gradients in peripersonal space and neglect severity
      (degree of lateral gradient) in extrapersonal space was also of interest. Right
      hemisphere stroke subjects, with and without neglect, and healthy control
      subjects named visual targets on scanning sheets placed in peripersonal and
      extrapersonal space. The neglect group showed lateral gradients of increasing
      target detection from left to right in both peripersonal and extrapersonal space,
      which were not evident in the performance of either of the control groups. Double
      dissociations of neglect severity in peripersonal and extrapersonal space were
      also found in analyses of individual performance. Lesion analyses showed that
      peripersonal neglect was related to dorsal stream damage and extrapersonal
      neglect was related to ventral stream damage. Group analyses showed no
      significant radial gradients in peripersonal space in the three groups. In
      addition, while analyses of some individuals found significant near-far and far
      near radial gradients, there was no correlation between radial gradients in
      peripersonal space and neglect severity in extrapersonal space. These results are
      discussed in terms of theorised hemispheric mechanisms of spatial attention and
      the relationship of neglect in the two co-ordinate spaces to the extent and
      location of damaged neurons in the right hemisphere.

PMID- 14670574
TI  - Dissociating person-specific from general semantic knowledge: roles of the left
      and right temporal lobes.
AB  - The cognitive architecture and neural underpinnings of different semantic domains
      remains highly controversial. We report two patients with focal temporal lobe
      atrophy who presented with contrasting and theoretically informative
      dissociations of person-specific versus general semantic knowledge. Subject J.P.
      showed severely impaired person-specific semantics, with relative preservation of
      knowledge about objects and animals, while subject M.A. exhibited the opposite
      pattern of performance (good knowledge of people in the context of impoverished
      general semantics). Voxel-based morphometric analysis of MR images in the two
      cases established predominantly right temporal atrophy associated with J.P.'s
      deficit for person knowledge and predominantly left temporal atrophy in M.A. who
      was impaired in general conceptual knowledge.

PMID- 14670575
TI  - Neuroimaging evidence for the emotional potency of odor-evoked memory.
AB  - To assess past behavioral reports of the emotional distinctiveness of odor-evoked
      memories, functional magnetic resonance imaging (fMRI) was used to compare
      regions of activation during recall triggered by olfactory and visual cues that
      were connected to a personally meaningful memory and a comparable control cue
      presented in olfactory and visual form. Five healthy right-handed females
      experienced both behavioral and fMRI memory testing. fMRI analyses indicated
      significantly greater activation in the amygdala and hippocampal regions during
      recall to the personally significant odor than any other cue, and behavioral
      responses confirmed that emotional responses were greatest to the personally
      meaningful odor. These findings provide convincing neurobiological evidence that
      the subjective experience of the emotional potency of odor-evoked memory is
      correlated with specific activation in the amygdala during recall and offers new
      insights into the affective organization of memory.

PMID- 14670576
TI  - What is odd in the oddball task? Prefrontal cortex is activated by dynamic
      changes in response strategy.
AB  - In the "oddball" target detection task, subjects respond to target stimuli that
      occur infrequently and irregularly within a series of standard stimuli. Although
      detection of these targets reliably evokes transient activity in prefrontal
      cortical regions, it has not been established whether this activity is due to
      selection of an infrequent response or to changes in response strategy. We
      investigated this issue using a novel variant of the oddball task that
      incorporated the Simon effect, while measuring hemodynamic brain activity in
      prefrontal cortex using functional magnetic resonance imaging (fMRI). Subjects
      viewed a series of circles and squares that required left and right button
      presses, respectively. On 90% of trials ("standard" trials), the stimuli were
      presented in the same visual hemifield as the hand of response, but on 10% of
      trials ("strategy-change" trials) they were presented in the opposite visual
      hemifield. Significant activation to the infrequent strategy-change trials was
      found in the anterior middle frontal gyrus (MFG), the posterior inferior frontal
      gyrus (IFG) and adjacent insular cortex, and in the anterior cingulate gyrus
      (ACG). These regions, which correspond to previous reports of oddball-related
      activation, were consistent across subjects. Behavioral results supported our
      interpretation that subjects potentiated a position-based response strategy,
      which was inhibited on the strategy-change trials. Activity within the MFG and
      ACG was much greater on error trials than on correct trials, while IFG activity
      was similar between error and correct trials. We conclude that the dorsolateral
      prefrontal cortex (dlPFC) is associated with dynamic changes in the mapping of
      stimuli to responses (e.g. response strategies), independently of any changes in
      behavior.

PMID- 14670577
TI  - The greyscales task: a perceptual measure of attentional bias following
      unilateral hemispheric damage.
AB  - The two cerebral hemispheres in humans have been suggested to control
      contralaterally opposed attentional biases. These biases may be revealed by
      unilateral hemispheric damage, which often causes contralesional spatial neglect,
      particularly when the right hemisphere (RH) is affected. Subtle attentional
      biases have also been observed in normal observers in tasks requiring judgements
      of horizontal spatial extent, brightness, numerosity and size. Here, we examined
      attentional biases for judging the darker of two left-right mirror-reversed
      brightness gradients under conditions of free viewing (the greyscales task). We
      compared performances of patients with damage to the RH (n=78) and left
      hemisphere (LH; n=20) with those of normal controls (n=20). Controls showed a
      small but significant leftward bias, implying a subtle asymmetry favouring the
      RH. In contrast, RH and LH patients showed extreme rightward and leftward biases,
      respectively, both of which differed significantly from that of controls. For the
      patient groups, performance on clinical tests of neglect (cancellation and line
      bisection) did not predict their greyscales scores. Pathological biases were
      present in patients without clinical neglect or visual field defects, suggesting
      that the attentional bias measured by the greyscales task can be dissociated from
      clinical neglect and visual sensory loss. The greyscales task offers an efficient
      means of quantifying pathological attentional biases in unilateral lesion
      patients; it is easy to administer and score, and may be particularly useful for
      clinical trials of recovery and rehabilitation following stroke.

PMID- 14670578
TI  - Functional MRI of visual-spatial processing in neurofibromatosis, type I.
AB  - Visual-spatial impairment and neuroanatomical abnormalities are considered
      hallmark features of neurofibromatosis, type I (NF-I). Numerous studies have
      demonstrated visual-spatial deficits in children with NF-I, but few relations
      between these deficits and neuroanatomical abnormalities have been identified. We
      compared the functional neuroanatomy of cerebral regions involved in the spatial
      transformation of alphanumeric stimuli in individuals with NF-I and healthy
      control participants using functional magnetic resonance imaging (fMRI). Given
      the prevalence of visual pathway abnormalities and visual-spatial deficits in NF
      I, we hypothesized that less neuronal hemodynamic activity would be found in
      occipital and parietal cortices in this group compared with controls. However, NF
      I participants relied to a greater degree than controls on posterior cortex
      (including occipital, parietal, and middle temporal cortices) relative to lateral
      and inferior frontal regions during visual-spatial analysis. This pattern was
      significantly related to their behavioral performance on the fMRI task, which in
      turn was also positively correlated with reading scores. These findings support
      evidence of frontal cortical anomalies in NF-I and may provide a
      pathophysiological basis for cognitive deficits in NF-I.

PMID- 14670579
TI  - Spared somatomotor and cognitive functions in a patient with a large
      porencephalic cyst revealed by fMRI.
AB  - To date functional magnetic resonance imaging (fMRI) has not been extensively
      used in presurgical evaluation of patients with intractable epilepsy. Patient
      S.P. presented with left frontal originating seizures, secondary to a large
      porencephalic cyst that encompassed much of his occipital and temporal cortex and
      a substantial portion of ipsilateral parietal cortex. Nevertheless, S.P. did not
      demonstrate any gross impairments of praxis or speech. Scalp electroencephalogram
      (EEG) telemetry revealed reduced background activity in the left hemisphere, an
      absence of identifiable normal sleep states, and confirmed the left frontal
      origin of his seizures with a prolonged postictal state, suggesting that the
      remaining cortex in S.P.'s left hemisphere did not function normally despite his
      apparently normal appearance. Dichotic listening results also suggested that S.P.
      had an atypical language representation suggestive of either bilateral or right
      hemisphere speech representation. Surgical intervention to remove the remaining
      left hemisphere cortex was a serious consideration for treatment of S.P.'s
      seizures. We used fMRI to evaluate whether or not the remaining cortex in S.P.'s
      left hemisphere supported any cognitive or motor functions. Even though the
      volume of cerebral cortex was severely reduced and displaced in the left
      hemisphere, fMRI revealed significant activation in this remaining tissue in
      response to motor, somatosensory, and word generation tasks. In other words, we
      were able to demonstrate using fMRI that the remaining tissue in S.P.'s left
      hemisphere continued to support some motor and cognitive functions. The possible
      implications of these findings in terms of functional reorganisation are
      discussed briefly.

PMID- 14670580
TI  - Treatment of herpes simplex virus infections.
AB  - Herpes simplex virus (HSV) types 1 and 2 are ubiquitous organisms that cause
      infections in human populations throughout the world. The clinical manifestations
      of HSV infections are varied, ranging from asymptomatic disease to life
      threatening illness in neonates and immunocompromised hosts. This article will
      review the common presentations for HSV disease and the current recommendations
      for the treatment of these infections. A detailed summary of the antiviral drugs
      used to treat HSV infections is also presented.

PMID- 14670581
TI  - Molecular analysis of clinical isolates of acyclovir resistant herpes simplex
      virus.
AB  - We characterised the antiviral phenotype and genotype of 41 herpes simplex virus
      (HSV) strains from patients clinically resistant to acyclovir (ACV). Our results
      confirm recognised mutational sites as being major determinants of thymidine
      kinase (tk)-associated ACV resistance, in particular insertions and/or deletions
      at homopolymer stretches of Gs and Cs (59% of all isolates). Previously described
      amino acid substitutions in functional sites of the tk were also identified (7%
      of all isolates). In addition, we identified several stop codons in novel
      locations on the amino acid sequence (7% of all isolates) and amino acid
      substitutions (15% of all isolates) likely to be directly responsible for
      conferring resistance to ACV. When there were no mutations detected in the tk
      gene (12% of all isolates), mutations in the DNA polymerase gene likely to be
      important in the generation of resistant virus were identified.

PMID- 14670582
TI  - Antiviral properties of hemocyanin isolated from shrimp Penaeus monodon.
AB  - Penaeid shrimp aquaculture has suffered from many diseases, especially from viral
      origin such as white spot syndrome virus (WSSV). In an attempt to obtain
      antiviral-relevant proteins, two peptides with molecular masses at 73 and 75kDa
      were isolated from shrimp Penaeus monodon using affinity chromatography coupled
      with the purified WSSV or a fish iridovirus (Singapore grouper iridovirus, SGIV),
      and identified as hemocyanin by mass spectrometry. The results, using fish
      viruses capable of cell culture, showed for the first time that the hemocyanin
      had non-specific antiviral properties and no cytotoxicity against host cells.

PMID- 14670583
TI  - Anti-HSV activity of lactoferricin analogues is only partly related to their
      affinity for heparan sulfate.
AB  - Earlier studies have shown that the heparan sulfate (HS) on the cell surface acts
      as a receptor for herpes simplex virus (HSV). We have recently shown that bovine
      lactoferricin (LfcinB), a small part of the milk protein lactoferrin, inhibits
      HSV-1 and HSV-2 infection, probably by blocking the entry of the virus. The human
      homologue (18-42), which shares 36% sequence similarity with LfcinB (17-41),
      displayed much lower antiviral activity. In the present study, a set of cyclic
      and linear human and bovine Lfcin derivatives were constructed to investigate the
      relation between their affinity to HS and chondroitin sulfate (CS) and their
      antiviral activity against HSV-1 and HSV-2. The lactoferrin (LF) proteins and
      several of the Lfcin derivatives exhibited similar affinity for HS, but the LF
      proteins possess a much higher antiviral activity than the smaller peptides. Our
      structure-activity relationship studies on the Lfcin derivates confirmed that
      affinity for HS, that was correlated to the net positive charge, is an important
      factor, but does not well predict the antiviral activity. Structural parameters
      such as hydrophobicity, molecular size, spatial distribution of charged and
      lipophilic amino acids, and the cyclic structure of Lfcin also seem to be
      important factors to govern antiviral activity against HSV.

PMID- 14670584
TI  - In vitro inhibition of Chikungunya and Semliki Forest viruses replication by
      antiviral compounds: synergistic effect of interferon-alpha and ribavirin
      combination.
AB  - Chikungunya virus (CHIKV) and Semliki Forest virus (SFV) were used in our
      laboratory to screen active antiviral compounds against viruses of the Alphavirus
      genus. Antiviral activity was estimated by the reduction of the cytopathic effect
      of each alphavirus on infected Vero cells and by virus titer reduction.
      Cytotoxicity was evaluated by determining the inhibition of Trypan blue exclusion
      in confluent cell cultures and by the evaluation of the inhibitory effect on cell
      growth. With CHIKV and SFV, the selectivity indices of human recombinant
      interferon-alpha and iota-carrageenan were much higher than that of ribavirin,
      which has been previously investigated for its inhibitory effect on alphavirus
      infections. Compared to ribavirin, 6-azauridine was more effective against CHIKV
      and showed a similar antiviral activity against SFV. IFN-alpha2b, glycyrrhizin, 6
      azauridine, and ribavirin caused a concentration-dependent reduction in the virus
      yield with CHIKV and SFV. Moreover, the combination of IFN-alpha2b and ribavirin
      had a subsynergistic antiviral effect on these two alphaviruses and should be
      evaluated for the treatment of these infections.

PMID- 14670585
TI  - No cross-resistance or selection of HIV-1 resistant mutants in vitro to the
      antiretroviral tripeptide glycyl-prolyl-glycine-amide.
AB  - The chemically modified tripeptide glycyl-prolyl-glycine-amide (GPG-NH(2))
      inhibits replication of HIV-1 in vitro, probably by interfering with capsid
      formation. This study was aimed at determining cross-resistance between
      antiretroviral drugs and GPG-NH(2), and whether resistance to GPG-NH(2) can be
      induced in vitro. Fifty-five clinical HIV-1 isolates with different resistance
      related mutations were tested for susceptibility to GPG-NH(2). No correlation
      between NRTI-, NNRTI- or PI-resistance and efficacy of GPG-NH(2) was found,
      indicating the lack of cross-resistance. Serial passages were performed with GPG
      NH(2), and with lamivudine, and genotypic or phenotypic changes were determined.
      Resistance to lamivudine was detected after six passages. No resistance to GPG
      NH(2) was generated after 30 passages in two parallel series. However, one
      mutation (T107I) in the p24 gene was detected in both series, but this mutation
      was not associated with decreased sensitivity to GPG-NH(2).

PMID- 14670586
TI  - Experimental study on the prevention and treatment of murine cytomegalovirus
      hepatitis by using allitridin.
AB  - Allitridin (diallyl trisulfide), a main effective compound of Allium sativum
      (garlic), was previously shown to inhibit the expression of immediate-early
      antigens and viral proliferation of human cytomegalovirus (HCMV) in vitro. Here
      we have examined the prophylactic and therapeutic efficacy of allitridin in a non
      lethal murine cytomegalovirus (MCMV) hepatitis in methylprednisolone
      immunosuppressed BALB/c mice. Allitridin was administered at 25mg/kg per day
      (equal to the mean human dose) and 75 mg/kg per day in two regimens: prophylaxis
      plus therapy beginning at 2 days before infection and lasting for 18 days, and
      therapy lasting for 14 days initiated at 2 days after infection. Ganciclovir
      (GCV)-treated, infected, and non-infected mice served as controls. MCMV DNA load
      in the liver, plasma alanine aminotransferase (ALT) level and Knodell's
      histological activity index (HAI) score of liver section were evaluated. We found
      that MCMV DNA load was significantly decreased in all allitridin- and GCV-treated
      mice, compared with infected controls. Concomitantly, histopathological lesions
      in the liver and plasma ALT levels were reduced. Statistically, no significant
      differences were detected between the combined allitridin prophylaxis plus
      therapeutic and therapeutic groups regardless of dose and the GCV groups. Our
      results demonstrate the therapeutic efficacy of allitridin in mouse models with
      MCMV hepatitis.

PMID- 14670587
TI  - Genotypic resistance profile in treatment-experienced HIV-infected individuals
      after abacavir and efavirenz salvage regimen.
AB  - Once highly active antiretroviral therapy (HAART) fails to suppress HIV
      replication and resistant viruses emerge, it is difficult to find a salvage
      regimen since cross-resistance is high among the available classes of
      antiretroviral drugs. In this retrospective analysis, genotypic resistance
      profiles were analysed in 24 patients who switched treatment to abacavir (ABV),
      efavirenz (EFV), and either a NRTI or a PI at baseline and after 24 weeks of
      treatment. At baseline, 71% of patients harboured at least one resistance
      mutation in the protease gene. In the RT gene, 87.5% of the patients showed
      nucleoside analogue resistance mutations, and an equal 87.5% showed resistance
      mutations to non-nucleoside analogues. After 24 weeks of treatment, only
      mutations to nucleoside analogues raised in 95.8% of the patients, while
      resistance mutations to the other drug classes remained constant. Substitutions
      conferring cross-resistance within each drug family were very common among this
      treatment-experienced population. These data also indicate that salvage therapy
      is likely to remain one of the most important issues in the treatment of HIV
      infections.

PMID- 14670588
TI  - Potent antiviral activity of amprenavir in primary macrophages infected by human
      immunodeficiency virus.
AB  - Objective of the present study was then to assess the antiviral activity of the
      protease inhibitor amprenavir in macrophages (M/M), and to compare it with its
      efficacy in peripheral blood lymphocytes (PBL). M/M were obtained from blood of
      sero-negative healthy donors and infected with M-tropic HIV-1 strain (HIV-1(Ba
      L)). The stabilized infection was assessed by monitoring the HIV-1 p24 gag
      antigen production in the supernatants of M/M cultures. In the setting of acute
      infection (treatment before HIV-1 challenge), amprenavir showed substantial
      activity both in M/M and PBL at similar concentrations (EC(50): 0.011 and 0.031
      microM, respectively); complete inhibition of HIV-1 replication was achieved in
      both cell types at concentration of about 2 microM. In the setting of chronical
      infection (i.e. antiviral treatment several days after established infection), an
      antiviral effect of amprenavir was achieved in M/M, but at concentrations higher
      than those active in acutely infected M/M (EC(50): 0.72 microM, EC(90): 18.2
      microM). The antiviral effect in chronically infected M/M was sustained for at
      least 2 weeks of continuous treatment. These findings suggest that amprenavir (at
      relatively high concentrations) has a clinically relevant antiviral effect in
      persistently infected reservoirs of HIV.

PMID- 14670589
TI  - A novel approach to develop anti-HIV drugs: adapting non-nucleoside anticancer
      chemotherapeutics.
AB  - Some anticancer drugs, but not all, inhibit replication of human immunodeficiency
      virus (HIV) and thus, exhibit a therapeutic potential. Such drugs, unlike the
      traditional HIV enzyme inhibitors, could suppress HIV strains that are resistant
      to inhibitors of viral enzymes, decrease proviral burden in vivo, or reduce
      reservoirs of infection via killing infected cells. Thus, they may be an
      effective adjunct therapy or perhaps result in a cure. The incidence of HIV
      infection and AIDS mortalities continue to increase worldwide, including the
      United States and parts of Africa, with a parallel increase in a number of other
      manifestations, including AIDS defining malignancies. The basis for continual
      spread of HIV presumably in large part stems from the viral resistance to
      previously successful drugs and the lack of curative antiretroviral drugs. To
      reverse these trends, other approaches for AIDS therapy must be developed. One
      possibility is the development of potent anticancer drugs, that exhibit anti-HIV
      activities. At least four chemically and pharmacologically distinct classes of
      anticancer drugs, i.e. certain cyclin-dependent kinase inhibitors (CDKIs),
      topoisomerase 1 enzyme (top 1) inhibitors, non-nucleoside antimetabolites, and
      estrogen receptor ligands are promising candidates. These drugs, at high doses
      are used for cancer therapy; at lower concentrations they exhibit anti-HIV
      activities in cultured cells. While the antiretroviral and the anticancer
      activities of the cdk inhibitor flavopiridol appear to be mutually exclusive and
      unrelated in cells and animal model(s) of HIV disease, the top 1 inhibitor 9
      nitrocamptothecin, as well as the cdk-inhibitor roscovitine inhibit replication
      of HIV via selective sensitization of HIV-infected cells to apoptosis. In
      contrast, the inhibitory effects of these compounds are different from other
      cancer therapeutics that, at toxic concentrations, activate HIV either in
      cultured cells (such as certain ingenol and butyrate derivatives) and/or in
      patients (such as the widely used cyclophosmamide and cisplatin). This quality
      may lead to the eradication of proviral reservoirs, which is not accomplished by
      the currently available antiretroviral drugs. In this review, relevant available
      clinical and in vitro data that either support or discourage using certain
      anticancer drugs for treatment of HIV disease, and the rationales for developing
      novel antiretroviral drugs that may target infected cells rather than viral
      proteins are discussed.

PMID- 14670590
TI  - Effect of topically applied resveratrol on cutaneous herpes simplex virus
      infections in hairless mice.
AB  - Resveratrol (3,5,4'-trihydroxystilbene) is a natural component of certain foods,
      such as grapes, that has been shown to have anti-herpes simplex virus (HSV)
      activity in vitro. To determine if it is active in vivo, the abraded epidermis of
      SKH1 mice were infected with HSV-1 and topically treated with 12.5 or 25%
      resveratrol cream or cream only. Initial studies demonstrated that: (1). 25%
      resveratrol cream topically applied two, three, or five times a day effectively
      suppressed lesion development whereas 12.5% resveratrol cream effectively
      suppressed lesion formation when applied five times a day starting 1h after
      infection; (2). when treatment was begun 1, 6, or 12h after infection, both 12.5
      and 25% resveratrol were effective at 1 and 6h after infection, but not if
      applied 12h after infection. Comparative studies between resveratrol cream, 10%
      docosanol cream (Abreva) and 5% acyclovir ointment (Zovirax) were also carried
      out. When treatment was begun 1h after infection and repeated every 3h five times
      a day for 5 days, 12.5 and 25% resveratrol significantly (P=0.0001) inhibited the
      development of HSV-1 induced skin lesions. Acyclovir was as effective (P=0.0001)
      as resveratrol. Animals that were topically treated with docosanol were not
      protected and developed lesions in a manner indistinguishable from cream only
      controls. These studies were repeated with an HSV-1 acyclovir-resistant virus. As
      before, 12.5 and 25% resveratrol cream effectively suppressed lesion formation.
      The skin of resveratrol-treated animals showed no apparent dermal toxicity such
      as erythema, scaling, crusting, lichenification, or excoriation. These studies
      demonstrate that topically applied resveratrol inhibits HSV lesion formation in
      the skin of mice.

PMID- 14670591
TI  - In vitro antiviral susceptibility of full-length clinical hepatitis B virus
      isolates cloned with a novel expression vector.
AB  - Analyses of drug susceptibility and replication capacity for clinical HBV
      isolates have been hampered by the limitations of available in vitro culture
      systems. Site-directed mutagenesis has been used to study the effects of point
      mutations in recombinant laboratory HBV strains, however, the validity of such
      analyses are compromised since mutations are removed from their natural genetic
      context. Here we report the development of a new plasmid vector that facilitates
      the cloning and expression of full-length HBV genomes amplified from the sera of
      chronic hepatitis B patients. Using this vector, we cloned a total of 28 full
      length HBV isolates from nine different patients. The majority of cloned HBV
      genomes ( approximately 70%) replicated in vitro and were suitable for further
      phenotypic characterization. Adefovir susceptibility was measured for clones from
      all nine patients. IC(50) values were similar to those previously obtained with
      standard laboratory HBV strains and did not vary significantly between individual
      patient isolates (mean IC(50)=0.24+/-0.08 microM). The vector described here
      enables the efficient phenotypic analysis of full-length HBV isolates from
      patients and will be useful in future studies including resistance surveillance,
      cross-resistance analyses, and novel drug-discovery.

PMID- 14670592
TI  - Interaction of sulfonated anionic porphyrins with HIV glycoprotein gp120:
      photodamages revealed by inhibition of antibody binding to V3 and C5 domains.
AB  - The key role of gp120 in the cellular entry of HIV makes this glycoprotein an
      attractive target for new drugs. Various polyanions bind to the positively
      charged V3 loop of gp120. Here, we consider a series of anionic porphyrins
      bearing two sulfonate groups and two carboxylic chains with various degree of
      esterification. These molecules carry an overall negative charge between 4 and 2.
      Upon activation by light, these compounds, known as photosensitizers, produce
      highly reactive oxygen species able to damage amino acid chains. The interactions
      of these molecules with the V3 loop and a positively charged area in the C5
      region were investigated in the dark by using specific antibodies and ELISA
      protocols. Competitive inhibition of the anti-V3 antibody was observed with an
      increased efficiency for the esterified compounds. No evidence for binding to the
      C5 region was found. In contrast, when gp120 was irradiated with light in
      presence of the porphyrin prior to the addition of the antibody, strong
      inhibition of the anti-C5 antibody was observed revealing irreversible photo
      damages in this region. No effect on the V3 loop was observed. Irradiations at
      two wavelengths made it possible to identify porphyrin monomers as the
      photoactive forms despite the presence of large excess of dimers in the
      incubation solution. It is suggested that porphyrins bound to the V3 loop could
      produce photo-damages at some distance, in particular within the C5 region that
      contains several photosensitive amino acids.

PMID- 14670593
TI  - Small interfering RNA molecules as potential anti-human rhinovirus agents: in
      vitro potency, specificity, and mechanism.
AB  - RNA silencing or interference (RNAi) is a sequence-specific, post-transcriptional
      process of mRNA degradation. The degradation of target gene mRNA can be induced
      by short dsRNA molecules (21-25-nt) corresponding to the sequence of the target
      gene to be silenced. Short dsRNA molecules have been shown to be very effective
      in inducing RNA silencing in several human cell lines. In this study, we have
      shown that short dsRNA molecules corresponding to the human rhinovirus-16 (HRV
      16) genome induce effective inhibition of the viral replication in cell culture.
      This inhibition is sequence-specific and dose-dependent. A single or double
      nucleotide sequence change in an effective dsRNA molecule can significantly
      reduce the ability of the molecule to induce RNA silencing. Reducing the length
      of siRNA molecules to 19-nt or shorter abolishes their activity. Therefore, the
      results of this study demonstrate certain siRNA molecules are inhibitory for the
      replication of HRV-16 when transfected into human cells; further studies are
      warranted to explore the potential clinical value of these siRNA molecules as
      anti-human rhinovirus agents.

PMID- 14670594
TI  - Antiviral activity of hop constituents against a series of DNA and RNA viruses.
AB  - We investigated whether crude hop extracts and purified hop components
      representing every major chemical class of hop compound have antiviral activity.
      These hop constituents were tested for antiviral activity against bovine viral
      diarrhea virus (BVDV) as a surrogate model of hepatitis C virus (HCV), human
      immunodeficiency virus (HIV), influenza A virus (FLU-A), influenza B virus (FLU
      B), rhinovirus (Rhino), respiratory syncytial virus (RSV), yellow fever virus
      (YFV), cytomegalovirus (CMV), hepatitis B virus (HBV), and herpes simplex virus
      type 1 (HSV-1) and type 2 (HSV-2). The extracts all failed to prevent the
      replication of HIV, FLU-A, FLU-B, RSV and YFV. A xanthohumol-enriched hop extract
      displayed a weak to moderate antiviral activity against BVDV (therapeutic index
      (TI)=6.0), HSV-2 (TI=>5.3), Rhino (TI=4.0) and HSV-1 (TI=>1.9) with IC(50) values
      in the low microg/ml range. Pure iso-alpha-acids demonstrated low to moderate
      antiviral activity against both BVDV (TI=9.1) and CMV (TI=4.2) with IC(50) values
      in the low microg/ml range. No antiviral activity was detected using beta-acids
      or a hop oil extract. Ultra-pure preparations (>99% pure) were used to show that
      xanthohumol accounted for the antiviral activity observed in the xanthohumol
      enriched hop extract against BVDV, HSV-1 and HSV-2. Xanthohumol was found to be a
      more potent antiviral agent against these viruses than the isomer iso
      xanthohumol. With Rhino, the opposite trend was observed with iso-xanthohumol
      showing superior antiviral activity to that observed with xanthohumol.
      Xanthohumol also showed antiviral activity against CMV, suggesting that it might
      have a generalized anti-herpesvirus antiviral activity. Again, superior antiviral
      activity was observed with the xanthohumol isomer against CMV. In summary, iso
      alpha-acids and xanthohumol were shown to have a low-to-moderate antiviral
      activity against several viruses. These hop constituents might serve as
      interesting lead compounds from which more active anti-HCV, anti-Rhino and anti
      herpesvirus antiviral agents could be synthesized.

PMID- 14670595
TI  - The cotton rat model for adenovirus ocular infection: antiviral activity of
      cidofovir.
AB  - To determine the antiviral effects of compounds against ocular adenovirus (AdV)
      infection, we established an animal model of AdV infection in cotton rat eyes.
      Cotton rat eyes were inoculated intrastromally and topically with four AdV
      serotypes 4, 5, 8, and 37, and treated topically with 1% HPMPC (cidofovir) eye
      drops twice a day. The infected corneas were extracted and homogenized, and virus
      titers in the cornea specimens were determined by a plaque assay. The virus titer
      in AdV type 5-inoculated eyes peaked on days 0 through 3 after inoculation and
      virus shedding was detected for 18.0+/-2.8 days. AdV 5 antigen in the infected
      corneas was demonstrated in the corneal epithelial cells by immunofluorescence
      stain. However, for AdV serotypes 4, 8, and 37, no evidence of continued virus
      replication in cotton rat eyes was noted. Specimens from cidofovir-treated eyes
      infected with AdV 5 demonstrated a statistically significant reduction in the
      mean virus titer (days 3-15) (P=0.028) and virus shedding duration (P=0.0014), as
      compared with those of the control group.

PMID- 14670596
TI  - Inhibitors of CTP biosynthesis potentiate the anti-human immunodeficiency virus
      type 1 activity of 3TC in activated peripheral blood mononuclear cells.
AB  - Unlike hydroxyurea, the CTP synthetase inhibitor acivicin and, to a lesser
      extent, two other inhibitors of CTP synthesis, increased the phosphorylation and
      anti-HIV-1 activity of 3TC in PHA-P-activated PBMC. These data suggest that to
      improve the antiretroviral activity of 3TC, it may be worth focusing on
      inhibition of CTP synthesis.

PMID- 14670597
TI  - Aspartate-186 in the head group of the yeast iron-sulfur protein of the
      cytochrome bc1 complex contributes to the protein conformation required for
      efficient electron transfer.
AB  - Two conserved charged amino acids, aspartate-186 and arginine-190, localized in
      the aqueous head region of the iron-sulfur protein of the cytochrome bc(1)
      complex of yeast mitochondria, were mutated to alanine, glutamate, or asparagine
      and isoleucine, respectively. The R190I mutation resulted in the complete loss of
      antimycin- and myxothiazol-sensitive cytochrome c reductase activity due to loss
      of more than 60% of the iron-sulfur protein in the complex. Mitochondria isolated
      from the D186A mutant had a 50% decrease in cytochrome c reductase activity but
      no loss of the iron-sulfur protein or the [2Fe-2S] cluster. The midpoint
      potential of the [2Fe-2S] cluster of the D186A mutant was decreased from 281 to
      178 mV. The D186E and D186N mutations did not result in a loss of cytochrome c
      reductase activity or content of iron-sulfur protein; however, the redox
      potential of the [2Fe-2S] cluster of D186N was decreased from 281 to 241 mV.
      Molecular modeling/dynamics studies predicted that substituting an alanine for
      Asp-186 causes global structural changes in the head group of the iron-sulfur
      protein resulting in changes in the orientation of the [2Fe-2S] cluster and
      consequently a lowered redox potential. The rate of electrogenic proton pumping
      in the bc(1) complex isolated from mutant D186A reconstituted into
      proteoliposomes decreased 64%; however, the H(+)/2e(-) ratio of 1.9 was identical
      in the mutant and the wild-type complexes. The carboxyl binding reagent, N
      (ethoxycarbonyl)-2-ethoxyl-1,2-dihydroquinoline (EEDQ) blocked electrogenic
      proton pumping in the bc(1) complex reconstituted into proteoliposomes without
      affecting electron transfer resulting in a decrease in the H(+)/2e(-) ratio to
      1.2 and 1.1, respectively. EEDQ was bound to the iron-sulfur protein and core
      protein II in both the wild type and the D186A mutant, indicating that Asp-186 of
      the iron-sulfur protein is not required for proton translocation in the bc(1)
      complex.

PMID- 14670598
TI  - The mitochondrial and prokaryotic proton-translocating NADH:ubiquinone
      oxidoreductases: similarities and dissimilarities of the quinone-junction sites.
AB  - The catalytic properties of the rotenone-sensitive NADH:ubiquinone reductase
      (Complex I) in bovine heart submitochondrial particles and in inside-out vesicles
      derived from Paracoccus denitrificans and Rhodobacter capsulatus were compared.
      The prokaryotic enzymes catalyze the NADH oxidase and NADH:quinone reductase
      reactions with similar kinetic parameters as those for the mammalian Complex I,
      except for lower apparent affinities for the substrates--nucleotides.
      Unidirectional competitive inhibition of NADH oxidation by ADP-ribose, previously
      discovered for submitochondrial particles, was also evident for tightly coupled
      P. denitrificans vesicles, thus suggesting that a second, NAD(+)-specific site is
      present in the simpler prokaryotic enzyme. The inhibitor sensitivity of the
      forward and reverse electron transfer reactions was compared. In P. denitrificans
      and Bos taurus vesicles different sensitivities to rotenone and Triton X-100 for
      the forward and reverse electron transfer reactions were found. In bovine heart
      preparations, both reactions showed the same sensitivity to piericidin, and the
      inhibition was titrated as a straight line. In P. denitrificans, the forward and
      reverse reactions show different sensitivity to piericidin and the titrations of
      both activities were curvilinear with apparent I(50) (expressed as mole of
      inhibitor per mole of enzyme) independent of the enzyme concentration. This
      behavior is explained by a model involving two different sites rapidly
      interacting with piericidin within the hydrophobic phase.

PMID- 14670599
TI  - N,N,N',N'-tetramethyl-p-phenylenediamine initiates the appearance of a well
      resolved I peak in the kinetics of chlorophyll fluorescence rise in isolated
      thylakoids.
AB  - Addition of N,N,N',N'-tetramethyl-p-phenylendiamine (TMPD) to thylakoid membranes
      isolated from pea leaves initiates the appearance of peak I in the polyphasic
      rise of chlorophyll (Chl) fluorescence observed during strong illumination,
      making it similar to that observed in leaves or intact chloroplasts. This effect
      depends on TMPD concentration and incubation period of isolated thylakoids with
      TMPD. The resolution of I-peak in the presence of weak concentrations of TMPD
      which reduced the overlap between I- and P-peaks, resulted from a decreased
      reduction of both fast and slow plastoquinone (PQ) pools of the granal and
      stromal thylakoids, respectively, as TMPD effectively accepts electrons from
      reduced PQ. High concentrations of TMPD markedly decreased the J-I-P phase of
      fluorescence rise and greatly retarded the I-P step rise. Accumulation of
      oxidized TMPD in the thylakoid lumen accelerated the re-oxidation of the acceptor
      side of Photosystem II (PSII) as illustrated by a two-fold increase in the
      magnitude of the fast component and complete suppression of the middle component
      of the variable Chl fluorescence (F(v)) decay in the dark. Evidently, exogenous
      addition of high concentrations of TMPD prevented the light-induced reduction of
      the slow PQ pool.

PMID- 14670600
TI  - Dependence of plastoquinol diffusion on the shape, size, and density of integral
      thylakoid proteins.
AB  - The diffusion of plastoquinol in the chloroplast thylakoid membrane is modelled
      using Monte Carlo techniques. The integral proteins are seen as obstacles to
      diffusion, and features of percolation theory emerge. Thus, the diffusion
      coefficient diminishes with increasing distance and there is a critical threshold
      of protein concentration, above which the long-range diffusion coefficient is
      zero. The area occupied by proteins in vivo is assessed and appears to be around
      this threshold, as determined from calculations assuming randomly distributed
      noninteracting proteins. Slight changes in the protein arrangement lead to
      pronounced changes in diffusion behaviour under such conditions. Mobility of the
      proteins increases the protein occupancy threshold, while boundary lipids
      impermeable to PQ diffusion decrease it. Further, the obstruction of
      plastoquinone/plastoquinol binding sites in a random arrangement is evaluated.

PMID- 14670601
TI  - Membrane potential, adenylate levels and Mg2+ are interconnected via adenylate
      kinase equilibrium in plant cells.
AB  - Concentrations of adenylate species and free magnesium (Mg(2+)) within cells are
      mediated by the equilibrium governed by adenylate kinase (AK), the enzyme
      abundant in plants in chloroplast stroma and intermembrane spaces of chloroplasts
      and mitochondria. Ratios of free and Mg-bound adenylates (linked to the values of
      [Mg(2+)] established under AK equilibrium) can be rationalized in terms of the
      overall dependence of concentrations of Mg(2+) and free and Mg-bound adenylates,
      as well as electric potential values across the inner membranes of mitochondria
      and chloroplasts. The potential across the inner mitochondrial membrane, by
      driving adenylate translocators, equilibrates free adenylates across the inner
      membrane according to the Nernst equation and contributes to the
      ATP(total)/ADP(total) ratio in the cytosol. The ratio affects the exchange of
      free adenylates with chloroplasts and this, in turn, influences the value of
      potential across the inner chloroplast membrane. From measurements of subcellular
      ATP(total)/ADP(total) ratios, we suggest a method of estimating the values of
      potential across inner membranes of mitochondria and chloroplasts in vivo, which
      allows a comparison of the operation of these organelles under different
      physiological conditions. We discuss also how the equilibration of adenylates by
      AK drives adenylate transport across membranes, and establishes [Mg(2+)] in the
      cytosol and chloroplast stroma, maintaining the rates of photosynthesis and
      respiration. This provides a tool for metabolomic research, by which the
      determined concentrations of adenylate species could be used for computation of
      essential metabolic parameters in the cell and in subcellular compartments.

PMID- 14670602
TI  - Kinetic analyses of state transitions of the cyanobacterium Synechococcus sp. PCC
      7002 and its mutant strains impaired in electron transport.
AB  - The state transitions of the cyanobacterium Synechococcus sp. PCC 7002 and of
      three mutant strains, which were impaired in PsaE-dependent cyclic electron
      transport (psaE(-)), respiratory electron transport (ndhF(-)) and both activities
      (psaE(-)ndhF(-)), were analyzed. Dark incubation of the wild type and psaE(-)
      cells led to a transition to state 2, while the ndhF(-) strains remained in state
      1 after dark incubation. The ndhF(-) cells adapted to state 2 when the cells were
      incubated under anaerobic conditions or in the presence of potassium cyanide;
      these results suggest that the ndhF(-) cells were inefficient in performing state
      1 to state 2 transitions in the dark unless cytochrome oxidase activity was
      inhibited. In the state 2 to state 1 transition of wild-type cells induced by
      light in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), there
      was still a significant reduction of the interphotosystem electron carriers by
      both respiration and cyclic electron flow around PSI. Kinetic analysis of the
      state 2 to state 1 transition shows that, in the absence of PSII activity, the
      relative contribution to the reduced state of the interphotosystem electron
      carriers by respiratory and cyclic electron transfer is about 72% and 28%,
      respectively. The state 2 to state 1 transition was prevented by the cytochrome
      b(6)f inhibitor 2,5-dibromo-3-methyl-6-isopropylbenzoquinone (DBMIB). On the
      other hand, the state 1 to state 2 transition was induced by DBMIB with half
      times of approximately 8 s in all strains. The externally added electron acceptor
      2,5-dimethyl-benzoquinone (DMBQ) induced a state 2 to state 1 transition in the
      dark and this transition could be prevented by DBMIB. The light-induced oxidation
      of P700 showed that approximately 50% of PSI could be excited by 630-nm light
      absorbed by phycobilisomes (PBS) under state 2 conditions. P700 oxidation
      measurements with light absorbed by PBS also showed that the dark-induced state 1
      to state 2 transition occurred in wild-type cells but not in the ndhF(-) cells.
      The possible mechanism for sensing an imbalanced light regime in cyanobacterial
      state transitions is discussed.

PMID- 14670603
TI  - Dissecting a cyanobacterial proteolytic system: efficiency in inducing
      degradation of the D1 protein of photosystem II in cyanobacteria and plants.
AB  - A chromatography fraction, prepared from isolated thylakoids of a fatty acid
      desaturation mutant (Fad6/desA Colon, two colons Km(r)) of the cyanobacterium
      Synechocystis 6803, could induce an initial cleavage of the D1 protein in
      Photosystem II (PSII) particles of Synechocystis 6803 mutant and Synechococcus
      7002 wild type as well as in supercomplexes of PSII-light harvesting complex II
      of spinach. Proteolysis was demonstrated both in darkness and in light as a
      reduction in the amount of full-length D1 protein or as a production of C
      terminal initial degradation fragments. In the Synechocystis mutant, the main
      degradation fragment was a 10-kDa C-terminal one, indicating an initial cleavage
      occurring in the cytoplasmic DE-loop of the D1 protein. A protein component of 70
      90 kDa isolated from the chromatographic fraction was found to be involved in the
      production of this 10-kDa fragment. In spinach, only traces of the corresponding
      fragment were detected, whereas a 24-kDa C-terminal fragment accumulated,
      indicating an initial cleavage in the lumenal AB-loop of the D1 protein. Also in
      Synechocystis the 24-kDa fragment was detected as a faint band. An antibody
      raised against the Arabidopsis DegP2 protease recognized a 35-kDa band in the
      proteolytically active chromatographic fraction, suggesting the existence of a
      lumenal protease that may be the homologue DegP of Synechocystis. The identity of
      the other protease cleaving the D1 protein in the DE-loop exposed on the stromal
      (cytoplasmic) side of the membrane is discussed.

PMID- 14670604
TI  - Properties of mutated Rhodospirillum rubrum H+-pyrophosphatase expressed in
      Escherichia coli.
AB  - The membrane-bound proton pumping inorganic pyrophosphate
      synthase/pyrophosphatase (H(+)-PPi synthase/H(+)-PPase) from the photosynthetic
      bacterium Rhodospirillum rubrum was functionally expressed in Escherichia coli
      C43(DE3) cells. Based on a new topology model of the enzyme, charged residues
      predicted to be located near or within the membrane were selected for site
      directed mutagenesis. Several of these mutations resulted in an almost complete
      inactivation of the enzyme. Four mutated residues appear to show a selective
      impairment of proton translocation and are thus likely to be involved in coupling
      pyrophosphate hydrolysis with electrogenic proton pumping. Two of these
      mutations, R176K and E584D, caused increased tolerance to salt. In addition, the
      former mutation caused an increased K(m) of one order of magnitude for the
      hydrolysis reaction. These results and their possible implications for the enzyme
      function are discussed.

PMID- 14670605
TI  - The dependence of algal H2 production on Photosystem II and O2 consumption
      activities in sulfur-deprived Chlamydomonas reinhardtii cells.
AB  - Chlamydomonas reinhardtii cultures, deprived of inorganic sulfur, undergo
      dramatic changes during adaptation to the nutrient stress [Biotechnol. Bioeng. 78
      (2002) 731]. When the capacity for Photosystem II (PSII) O(2) evolution decreases
      below that of respiration, the culture becomes anaerobic [Plant Physiol. 122
      (2000) 127]. We demonstrate that (a) the photochemical activity of PSII,
      monitored by in situ fluorescence, also decreases slowly during the aerobic
      period; (b) at the exact time of anaerobiosis, the remaining PSII activity is
      rapidly down regulated; and (c) electron transfer from PSII to PSI abruptly
      decreases at that point. Shortly thereafter, the PSII photochemical activity is
      partially restored, and H(2) production starts. Hydrogen production, which lasts
      for 3-4 days, is catalyzed by an anaerobically induced, reversible hydrogenase.
      While most of the reductants used directly for H(2) gas photoproduction come from
      water, the remaining electrons must come from endogenous substrate degradation
      through the NAD(P)H plastoquinone (PQ) oxido-reductase pathway. We propose that
      the induced hydrogenase activity provides a sink for electrons in the absence of
      other alternative pathways, and its operation allows the partial oxidation of
      intermediate photosynthetic carriers, including the PQ pool, between PSII and
      PSI. We conclude that the reduced state of this pool, which controls PSII
      photochemical activity, is one of the main factors regulating H(2) production
      under sulfur-deprived conditions. Residual O(2) evolved under these conditions is
      probably consumed mostly by the aerobic oxidation of storage products linked to
      mitochondrial respiratory processes involving both the cytochrome oxidase and the
      alternative oxidase. These functions maintain the intracellular anaerobic
      conditions required to keep the hydrogenase enzyme in the active, induced form.

PMID- 14670606
TI  - Interaction of oxyanions with thioredoxin-activated chloroplast coupling factor
      1.
AB  - Interaction between F(1)-ATPase activity stimulating oxyanions and noncatalytic
      sites of coupling factor CF(1) was studied. Carbonate, borate and sulfite anions
      were shown to inhibit tight binding of [14C]ATP and [14C]ADP to CF(1)
      noncatalytic sites. The demonstrated change of their inhibitory efficiency in
      carbonate-borate-sulfite order coincides with the previously found change in
      efficiency of these anions as stimulators of CF(1)-ATPase activity [Biochemistry
      (Mosc.) 43 (1978) 1206-1211]. Inhibition of tight nucleotide binding to
      noncatalytic sites was accompanied by stimulation of nucleotide binding to
      catalytic sites. This suggests that stimulation of CF(1)-ATPase activity is
      caused by interaction between oxyanions and noncatalytic sites. A most efficient
      stimulator of CF(1)-ATPase activity, sulfite oxyanion, appeared to be a
      competitive inhibitor with respect to ATP and a partial noncompetitive inhibitor
      with respect to ADP. The inhibition weakened with increasing time of CF(1)
      incubation with sulfite and nucleotides. Sulfite is believed to inhibit fast
      reversible interaction between nucleotides and noncatalytic sites and to produce
      no effect on subsequent tight binding of nucleotides. A possible mechanism of the
      oxyanion-stimulating effect is discussed.

PMID- 14670607
TI  - FRET reveals changes in the F1-stator stalk interaction during activity of F1F0
      ATP synthase.
AB  - A stator is proposed as necessary to prevent futile rotation of the F(1)
      catalytic sector of mitochondrial ATP synthase (mtATPase) during periods of ATP
      synthesis or ATP hydrolysis. Although the second stalk of mtATPase is generally
      believed to fulfil the role of a stator capable of withstanding the stress
      produced by rotation of the central rotor, there is little evidence to directly
      support this view. We show that interaction between two candidate proteins of the
      second stalk, OSCP and subunit b, fused at their C-termini to GFP variants and
      assembled into functional mtATPase can be monitored in mitochondria using
      fluorescence resonance energy transfer (FRET). Substitution of native OSCP with a
      variant containing a glycine 166 to asparagine (G166N) substitution yielded a
      metastable complex. In contrast to the enzyme containing native OSCP, FRET could
      be irreversibly lowered for the enzyme containing G166N at a rate that correlated
      closely with the rate of enzyme activity (ATP hydrolysis). The non-hydrolysable
      ATP analogue, AMP-PCP did not have this effect. We conclude that two candidate
      proteins of the stator stalk, OSCP and b, are subject to stresses during enzyme
      catalytic activity commensurate with their role as a part of a stator stalk.

PMID- 14670608
TI  - Each yeast mitochondrial F1F0-ATP synthase complex contains a single copy of
      subunit 8.
AB  - The stoichiometry of subunit 8 in yeast mitochondrial F(1)F(0)-ATP synthase
      (mtATPase) has been evaluated using an immunoprecipitation approach. Single HA or
      FLAG epitopes were introduced at the N-terminus of subunit 8. Expression of each
      tagged subunit 8 variant in yeast cells lacking endogenous subunit 8 restored a
      respiratory phenotype and had little measurable effect on ATP hydrolase activity
      of the isolated enzyme. Moreover, the two epitope-tagged subunit 8 variants could
      be stably co-expressed in the same host cells and both of HA-Y8 and FLAG-Y8 could
      be detected in ATP synthase complexes isolated by native gel electrophoresis.
      Mitochondria isolated from each yeast strain were solubilized to release ATP
      synthase complexes in either the monomeric or dimeric forms. In each case,
      monoclonal antibodies directed against either the FLAG or HA epitope could
      immunoprecipitate intact ATP synthase complexes. When both HA-Y8 and FLAG-Y8 were
      co-expressed in cells, monomeric ATP synthases contained only a single subunit 8
      variant after immunoprecipitation, corresponding to the particular antibody used
      (HA or FLAG). By contrast, both subunit 8 variants were recovered in samples of
      immunoprecipitated dimeric ATP synthase complexes, irrespective of the antibody
      used. We conclude that each monomeric yeast mitochondrial ATP synthase complex
      contains a single copy of subunit 8.

PMID- 14670609
TI  - Monitoring cytochrome redox changes in the mitochondria of intact cells using
      multi-wavelength visible light spectroscopy.
AB  - We have developed an optical system based on visible light spectroscopy for the
      continuous study of changes in the redox states of mitochondrial cytochromes in
      intact mammalian cells. Cells are suspended in a closed incubation chamber in
      which oxygen and nitric oxide (NO) concentrations can be monitored during
      respiration. Simultaneously the cells are illuminated with a broad-band tungsten
      halogen light source. Emergent light in the visible region (from 490-650 nm) is
      detected using a spectrophotometer and charge-coupled device camera system.
      Intensity spectra are then converted into changes in optical attenuation from a
      'steady-state' baseline. The oxidised-minus-reduced absorption spectra of the
      mitochondrial cytochromes are fitted to the attenuation spectra using a multi
      wavelength least-squares algorithm. Thus, the system can measure changes in the
      redox states of the cytochromes during cellular respiration. Here we describe
      this novel methodology and demonstrate its validity by monitoring the action of
      known respiratory chain inhibitors, including the endogenous signalling molecule
      NO, on cytochrome redox states in human leukocytes.

PMID- 14670610
TI  - The crystal structure of the spinach plastocyanin double mutant G8D/L12E gives
      insight into its low reactivity towards photosystem 1 and cytochrome f.
AB  - Plastocyanin (Pc) is a copper-containing protein, which functions as an electron
      carrier between the cytochrome b(6)f and photosystem 1 (PS1) complexes in the
      photosynthetic electron transfer (ET) chain. The ET is mediated by His87 situated
      in the hydrophobic surface in the north region of Pc. Also situated in this
      region is Leu12, which mutated to other amino acids severely disturbs the ET from
      cytochrome f and to PS1, indicating the importance of the hydrophobic surface.
      The crystal structure of the Pc double mutant G8D/L12E has been determined to 2.0
      A resolution, with a crystallographic R-factor of 18.3% (R(free)=23.2%). A
      comparison with the wild-type structure reveals that structural differences are
      limited to the sites of the mutations. In particular, there is a small but
      significant change in the hydrophobic surface close to His87. Evidently, this
      leads to a mismatch in the reactive complex with the redox partners. For PS1 this
      results in a 20 times weaker binding and an eightfold slower ET as determined by
      kinetic measurements. The mutations that have been introduced do not affect the
      optical absorption spectrum. However, there is a small change in the EPR
      spectrum, which can be related to changes in the copper coordination geometry.

PMID- 14670611
TI  - Computer simulation of cytoplasmic pH regulation mediated by the F-type H+
      ATPase.
AB  - Cytoplasmic pH regulation mediated by the H(+)-ATPase was examined with the aid
      of computer simulation. The data obtained with our simulation model were
      consistent with the experimental data and the simulation clarified the following
      points that may be difficult to be clarified with experimental studies. (1) The
      change in the enzyme amount controlled by cytoplasmic pH was essential for the pH
      regulation. (2) No significant change in internal pH was observed in acidic
      surroundings even if the proton transport activity of the H(+)-ATPase changed
      greater than sixfold. (3) The cytoplasmic pH homeostasis can be maintained even
      when the biosynthetic rate of the enzyme decreased by 50%. These results
      suggested that this regulatory system has an ability to maintain the pH in
      homeostasis even under harsh conditions that decrease cellular metabolic
      activities.

PMID- 14670612
TI  - Alterations of pRb1-cyclin D1-cdk4/6-p16(INK4A) pathway in endometrial
      carcinogenesis.
AB  - The retinoblastoma protein pathway (pRb1-cyclin D1-cdk4/6-p16(INK4A))
      participates in the regulation of the cellular processes at the transition of
      G1/S phases of the cell-cycle. Derailments of this pathway, caused either by lack
      of pRb1 or p16(INK4A) expression or overexpression of cyclin D1 and/or cdk4/6,
      are implicated in the deregulation of the cell-cycle machinery, resulting in
      uncontrolled cell proliferation, tumor heterogeneity, invasion and metastasis.
      Several studies conducted so far have assessed the deregulation of the pRb1
      pathway components in various human tumors and cell-lines, provided these pathway
      alterations play an obligatory role in tumorigenesis. This review briefly
      summarizes the current information on the pRb1-cyclin D1-cdk4/6-p16(INK4A)
      alterations in sporadic uterine cancer, placing emphasis on the influence on the
      dualistic model of endometrial carcinogenesis.

PMID- 14670613
TI  - Psyllium extracts decreased neoplastic phenotypes induced by the Ha-Ras oncogene
      transfected into a rat liver oval cell line.
AB  - Inhibition of gap junctional intercellular communication (GJIC) by tumor
      promoters and oncogenes has been implicated in the removal of initiated cells
      from the suppression of growth by neighboring cells in the tumor promoting step
      of carcinogenesis. The GJIC of WB-Ha-ras cell line is GJIC-deficient and they are
      capable of anchorage independent growth (AIG). The ethanol extract of psyllium
      increased GJIC 1.65-times and decreased AIG in both number and size of colonies
      in WB-Ha-ras cells. Histochemical staining of the gap junction protein,
      connexin43, showed that psyllium restored gap junction plaques on the plasma
      membrane of the WB-Ha-ras cells. In conclusion, the ethanol extract of psyllium
      reversed two tumor cell phenotypes, namely reduced GJIC and AIG, induced by the
      Ha-ras oncogene.

PMID- 14670614
TI  - Peroxisome proliferator-activated receptors (PPARs) and associated transcription
      factors in colon cancer: reduced expression of PPARgamma-coactivator 1 (PGC-1).
AB  - Peroxisome proliferator-activated receptors (PPARs) alpha,beta/delta and gamma
      are fatty acid sensitive transcription factors that have been implicated in
      colorectal cancer. To better understand their role, we studied the expression
      levels of all PPAR-isoforms and transcriptional partners such as the retinoid X
      receptor alpha (RXRalpha) and PPARgamma-coactivator-1 (PGC-1) by means of real
      time PCR in 17 patients with colon cancer. While a heterogeneous pattern was
      observed for the expression level of the PPAR-isoforms alpha,beta/delta and
      gamma, the coactivator PGC-1 was significantly decreased in 15 of 17 tumors.
      Taken together our data suggest that the transcriptional activity of PPARgamma
      may not only be decreased by mutation but also by downregulation of the
      coactivator PGC-1 of PPARgamma.

PMID- 14670615
TI  - Induction of medulloblastoma cell apoptosis by sulforaphane, a dietary
      anticarcinogen from Brassica vegetables.
AB  - There is increasing evidence that a variety of natural substances derived from
      the diet may act as potent chemopreventive agents. In this work, we show that
      DAOY cells, a widely used model of metastatic medulloblastoma (MBL), are highly
      sensitive to sulforaphane, a naturally occurring isothiocyanate from Brassica
      vegetables. Sulforaphane induced DAOY cell death by apoptosis, as determined by
      DNA fragmentation and chromatin condensation. DAOY apoptosis correlates with the
      induction of caspase-3 and -9 activities, resulting in the cleavage of PARP and
      vimentin. Both the cytotoxic effect and apoptotic characteristics induced by
      sulforaphane were reversed by zVAD-fmk, a broad spectrum caspase inhibitor,
      demonstrating the important role of caspases in its cytotoxic effect. These
      results identify sulforaphane as a novel inducer of MBL cell apoptosis,
      supporting the potential clinical usefulness of diet-derived substances as
      chemopreventive agents.

PMID- 14670616
TI  - Carcinosarcoma-induced endothelial cells tube formation through KDR/Flk-1 is
      blocked by TNP-470.
AB  - We evaluated the usefulness of TNP-470 as an anti-cancer agent on a human uterine
      carcinosarcoma cell line (FU-MMT-1). FU-MMT-1 induced human arterial endothelial
      cell (HAEC) tube formation on an in vitro co-cultured model of FU-MMT-1 and HAECs
      on a matrix gel, and was blocked by vascular endothelial growth factor (VEGF)-2
      receptor (KDR/Flk-1) tyrosine kinase inhibitor. Lower concentration of TNP-470
      inhibited the tube formation. Cell proliferation of FU-MMT-1 but not HAEC was
      inhibited by lower concentration of TNP-470. In addition, lower concentration of
      TNP-470 blocked VEGF production on FU-MMT-1. Our results suggest that TNP-470
      directly inhibited FU-MMT-1 but not HAEC growth accompanied with the inhibition
      of VEGF production, subsequently induced anti-angiogenesis on HAEC.

PMID- 14670617
TI  - Insertion of an exogenous promoter in the E1A regulatory region of adenovirus
      does not disturb viral replication despite reduced E1A transcription.
AB  - Insertion of an exogenous promoter into adenoviral regulatory regions may result
      in altered specificity and activity of the integrated promoter-mediated
      transcription in the context of recombinant adenoviruses (Ad). The alteration is
      due to the influence of the viral regulatory elements. Specificity of oncolytic
      Ad, in which the E1A expression is designed to be controlled by a tumor-specific
      promoter, could thus be modulated by the Ad E1A enhancer/promoters. We prepared
      recombinant Ad bearing a midkine (MK) promoter region in the 3'-side of the E1A
      promoter and investigated the relationship between transcriptional activity by
      the E1A promoter-fused MK fragment and the viral replication. Reporter assays
      revealed that the transcriptional activity of the fused E1A-MK fragment was
      significantly lower than that of respective E1A and the MK promoters. However,
      the replication of the Ad bearing the MK promoter was greater than or comparable
      to that of wild-type Ad. The present study suggests that the replication of
      oncolytic Ad in tumors is not directly correlated with the promoter activity to
      transcribe the E1A gene and that insertion of an exogenous promoter downstream to
      the E1A regulatory region may not always disturb Ad replication.

PMID- 14670618
TI  - Cytostatic and cytotoxic activity of synthetic genistein glycosides against human
      cancer cell lines.
AB  - Genistein, the principal soy isoflavone, is a molecule of great interest as an
      innovative chemotherapeutic agent or as a lead-compound in anticancer drug
      design. To enhance intrinsic activity of genistein and to explore its
      pharmacophoric potential, its glycosidic derivatives were synthesized. On the
      basis of structural features and calculated lipophilicity coefficient (ClogP) the
      derivatives were classified as hydrophilic (i.e. those containing free sugar
      moiety) or lipophilic (i.e. those with alkylated or acylated sugar hydroxyls).
      The in vitro cytostatic and cytotoxic studies showed hydrophilic glycosides to be
      practically inactive against human cancer cell lines when compared to the free
      aglycone. On the contrary, lipophilic glycosides were significantly more active
      than the parent isoflavone although the correlation between ClogP and the
      activity was not clear. On the basis of GI50 and LC50 values two of the most
      active glycosides were found to be several times more potent in their cytostatic
      and cytotoxic effect than genistein. Additionally all lipophilic glycosides were
      revealed to exhibit different mode of action in comparison to genistein. It may
      suggest that these compounds do not undergo rapid biodegradation, either in
      culture media or inside cells, and exert their biological effects primarily as
      intact molecules.

PMID- 14670619
TI  - Frequent loss of heterozygosity on chromosome 9 in Chinese esophageal squamous
      cell carcinomas.
AB  - Multiple and extensive alterations in chromosome 9 were detected in thirty-four
      esophageal squamous cell carcinoma patients, using seventeen polymorphic markers
      localized to chromosome 9 to detect the loss of heterozygosity (LOH) by
      polymerase chain reaction techniques. The LOH rates detected in this study range
      from 42.9 to 80.0%. Three commonly deleted regions mapping to 9p23-p22, 9q13
      q22.3, and 9q34 were observed. D9S1812 LOH at 9q22.1 was significantly associated
      with well- and moderately-differentiated tumors; LOH at D9S768, mapping to 9q13
      21.3, indicated that drinking habits are not a significant risk factor for
      Chinese esophagus cancer. Interestingly, no case of microsatellite instability
      was observed.

PMID- 14670620
TI  - Chromosomal end-to-end fusions in immortalized mouse embryonic fibroblasts
      deficient in the DNA-dependent protein kinase catalytic subunit.
AB  - Telomeres constitute the ends of the linear eukaryotic chromosomes and are
      essential for the maintenance of chromosome stability and genome integrity. One
      of the consequences of an altered telomere structure is the formation of
      telomeric fusions (TFs), that is aberrant chromosomes in which two elements are
      fused at their telomeres. Proteins involved in the non-homologous end joining
      pathway for the repair of the DNA double strand breaks, as the DNA-dependent
      protein kinase catalytic subunit (DNA-PKcs), contribute to the formation of a
      functional telomere. To investigate the role of DNA-PKcs in telomere
      functionality, we studied the frequency of TFs in mouse embryonic fibroblasts
      obtained from animals in which the DNA-PKcs gene had been inactivated; the
      analysis was performed prior and after spontaneous immortalization in culture.
      Our results suggest that DNA-PKcs deficiency has a limited effect, if any, on TF
      formation in primary cells, while it further increases chromosomal instability in
      immortalized cells. In fact, the frequency of TFs was significantly higher in
      immortalized DNA-PKcs mutant cells compared to wild type cells. Together with
      TFs, we also found metacentric or submetacentric chromosomes in which no
      telomeric sequences were detected at the joining site. The frequency of this
      anomaly, that resembles the Robertsonian translocations observed in wild mice,
      was independent of the DNA-PKcs genotype. This suggests that the formation of
      these rearranged chromosomes does not rely on a functional DNA-PKcs.

PMID- 14670621
TI  - Chromosome 7q31 allelic imbalance and somatic mutations of RAY1/ST7 gene in
      colorectal cancer.
AB  - ST7 is a putative tumor suppressor gene on chromosome 7q31. However, the role of
      ST7 as a tumor suppressor is uncertain as somatic mutations have been difficult
      to demonstrate. In order to investigate the genetic role of RAY1/ST7 in
      tumorigenesis, we have screened 135 colorectal cancers for loss of heterozygosity
      (LOH) at chromosome 7q31. The entire RAY1/ST7 gene, including intron/exon
      boundaries and alternate 5' and 3' sequences of 15/124 (12%) informative cancers
      with LOH were characterized. No somatic mutations of the RAY1/ST7 gene were
      observed. Our results do not support a role for RAY1/ST7 as a colorectal cancer
      tumor suppressor gene.

PMID- 14670622
TI  - 2-Acetylaminofluorene inhibits interleukin-1beta production in LPS-stimulated
      macrophages by blocking NF-kappaB/Rel activation.
AB  - In the present study, we demonstrate the inhibitory effect of 2
      acetylaminofluorene (AAF) on interleukin-1beta (IL-1beta) gene expression in
      lipopolysaccharide (LPS)-stimulated macrophages. Acetylaminofluorene inhibited IL
      1 production in LPS-stimulated splenic macrophages and RAW 264.7 cells.
      Additionally, AAF also suppressed LPS-induced mRNA expression of IL-1beta in
      macrophages. To further characterize the molecular mechanism responsible for AAF
      mediated suppression of IL-1beta, we investigated the effect of AAF on LPS
      mediated activation of transcription factors, such as NF-kappaB, AP-1, CRE and NF
      IL6, which are known to be important for LPS-induced gene expression of IL-1beta.
      Treatment of AAF caused a dose-related inhibition of LPS-induced NF-kappaB/Rel
      transcriptional activation, while the transcriptional activation of AP-1, CRE and
      NF-IL6 was not affected by AAF. Furthermore, LPS-induced NF-kappaB/Rel DNA
      binding was also suppressed by AAF treatment. These results suggest that AAF
      inhibits IL-1beta gene expression by blocking NF-kappaB/Rel activation.

PMID- 14670623
TI  - Differential regulation of vimentin mRNA by 12-O-tetradecanoylphorbol 13-acetate
      and all-trans-retinoic acid correlates with motility of Hep 3B human
      hepatocellular carcinoma cells.
AB  - Vimentin is a growth-related gene and often expressed when epithelial cells are
      stimulated to proliferate by growth factors. In cancer, vimentin expression is
      associated with a dedifferentiated malignant phenotype, increased motility,
      invasive ability and poor prognosis. We studied the regulation of vimentin mRNA
      and multistep invasion processes following treatment of 12-O-tetradecanoylphorbol
      13-acetate (TPA) and all-trans-retinoic acid (RA) in Hep 3B hepatocellular
      carcinoma cells. TPA showed marked induction of vimentin mRNA, while RA decreased
      the mRNA level. TPA or RA did not affect cell proliferation, cell-matrix protein
      adhesion, and matrix metalloproteinases and urokinase plasminogen activator
      activities. In vitro invasion ability was significantly increased or decreased
      with TPA or RA treatment, paralleled to the in vitro motile activity,
      respectively. These findings suggest that TPA and RA could modulate the invasive
      potential of Hep 3B cells by altering cellular motility related to differential
      regulation of vimentin mRNA.

PMID- 14670624
TI  - Mutant p53 protein in the serum of patients with cervical carcinoma: correlation
      with the level of serum epidermal growth factor receptor and prognostic
      significance.
AB  - We have previously reported that the serum level of epidermal growth factor
      receptor (EGFR) was significantly elevated in 38 cervical carcinoma patients. The
      levels of mutant p53 protein were determined in the serum of the same cohort
      (invasive or recurrent carcinoma: 26, carcinoma in situ (CIS): 12) and 18
      controls using ELISA. The median serum level for mutant p53 in cervical carcinoma
      patients (0.11 ng/ml; range, 0-2.66 ng/ml) demonstrated no significant difference
      compared to that of controls (0.14 ng/ml; range, 0-0.34 ng/ml) (P=0.324). Serum
      mutant p53 showed positive elevation in 5 patients with invasive or recurrent
      carcinoma (19%) and 1 with CIS (8%). A significant correlation was found between
      EGFR and mutant p53 levels (r=0.668; P<0.0001). In invasive or recurrent cervical
      carcinoma, positive mutant p53 was significantly associated with poor overall
      survival in both univariate (P=0.035) and multivariate (P=0.046) analysis, while
      increased level of EGFR did not show prognostic significance (P=0.755). Serum
      mutant p53 could have potential usefulness as a biological marker of cervical
      carcinoma for prediction of prognosis and follow-up after treatment.

PMID- 14670625
TI  - The PARP inhibitor benzamide protects against kainate and NMDA but not AMPA
      lesioning of the mouse striatum in vivo.
AB  - Overactivation of poly(ADP-ribose) polymerase (PARP) in response to genotoxic
      insults can cause cell death by energy deprivation. We previously reported that
      neurotoxic amounts of kainic acid (KA) injected into the rat striatum produce
      time-dependent changes in striatal PARP activity in vivo. Here, we have
      investigated the time-course of KA-induced toxicity and the effects of the PARP
      inhibitor benzamide on KA, AMPA and NMDA neurotoxicities in vivo, by measuring
      changes in the volume of the lesion and in NAD+ and ATP levels induced by the
      intra-striatal injection of these excitotoxins in C57Bl/6N mice. The KA-induced
      lesion volume was dependent on the amount of toxin injected and the survival
      time. The lesion was well developed at 48 h and was almost undetectable after one
      week. KA produced an extensive astrogliosis at one week. Benzamide partially
      prevented both KA- and NMDA- but not AMPA-induced lesions when measured at 48 h
      after the treatment. The effects of benzamide appeared to be in part related to
      changes in energy metabolism, since KA produced decreases in striatal levels of
      NAD+ and ATP that were partially prevented by benzamide at 48 h and which
      returned to control levels at one week. NMDA did not affect NAD+ and induced
      little alteration in ATP levels. Benzamide had no effect on AMPA-induced
      decreases in either NAD+ or ATP levels at 48 h. These results (1) indicate that
      PARP overactivation and energy depletion could be responsible in part for the
      cellular demise during the development of the lesion induced by KA; (2) confirm
      that PARP is involved in NMDA but not AMPA toxicities; (3) suggest the existence
      of differences between KA and AMPA-mediated toxicities; and (4) provide further
      evidence supporting PARP as a novel target for new drug treatments against
      neurodegenerative disorders.

PMID- 14670626
TI  - A serotonergic (5-HT2) receptor mechanism in the laterodorsal tegmental nucleus
      participates in regulating the pattern of rapid-eye-movement sleep occurrence in
      the rat.
AB  - Serotonin [5-hydroxytryptamine (5-HT)] plays an inhibitory role in rapid-eye
      movement (REM) sleep although the exact mechanism(s) and site(s) of action are
      not known. It is commonly assumed that 5-HT exerts its influence on REM sleep via
      input from the dorsal raphe nucleus (DRN) directly onto cholinergic neurons
      involved in the generation of REM sleep. 5-HT(2) receptor sites have been found
      on cholinergic neurons in the laterodorsal tegmental nucleus (LDT) and
      pedunculopontine tegmental nucleus (PPT). We locally microinjected the 5-HT(2)
      agonist DOI ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl) and the 5
      HT(2) antagonist, ketanserin, in LDT in rats to determine whether these receptor
      sites are involved in the regulation of behavioral states. DOI and ketanserin
      primarily affected REM sleep, by significantly decreasing or increasing,
      respectively, the number, but not the duration, of REM sleep episodes. DOI
      specifically decreased the occurrence of clusters of REM sleep episodes appearing
      at intervals less than or equal to 3 min (sequential episodes) without affecting
      single episodes separated by more than 3 min. An opposite effect of ketanserin on
      REM sleep clusters, although not statistically significant, was observed.

PMID- 14670627
TI  - Comparative analyses of synaptic densities during reactive synaptogenesis in the
      rat dentate gyrus.
AB  - Advancements in the field of synaptic plasticity have created the need for a
      reexamination of classic paradigms using new and more precise techniques. One
      prime candidate for such a reexamination is the process of reactive
      synaptogenesis (RS). Since the time course of RS was initially outlined in the
      1970s and 1980s, advances in stereology have allowed for better characterization
      of synaptic ultrastructure. Thus, a reexamination was undertaken in the
      hippocampal dentate gyrus by assessing the densities and proportions of several
      synaptic subtypes in Long-Evans hooded rats at 3, 6, 10, 15 and 30 days following
      induction of unilateral lesions of the entorhinal cortex. Although initial
      synaptic loss in the denervated region was similar to previous reports, recovery
      during the first 30 days is not as dramatic as previously observed. Following
      lesioning, concave and perforated synapses retained pre-lesion density despite
      massive degeneration, underscoring their theoretical importance in plasticity and
      maintenance of neural function. Convex synapses showed opposite changes, having
      implications for excitation/inhibition imbalance following lesion induction.
      These complementary alterations in synaptic structures support ultrastructural
      changes as a means for compensation following synaptic loss. Nearby areas also
      seem to participate in this response, with a striking similarity to other models
      of plasticity, such as long-term potentiation.

PMID- 14670628
TI  - Infusions of midazolam into the medial prefrontal cortex produce anxiolytic
      effects in the elevated plus-maze and shock-probe burying tests.
AB  - Previous research has shown that lesions of the medial prefrontal cortex (MPFC)
      inhibit fear-related behavior in rats (Brain Res. 969 (2003) 183-194). However,
      at present little is known about the role of specific neurotransmitter receptor
      systems within the MPFC in the mediation of fear and anxiety. For example,
      extensive research has demonstrated the effectiveness of benzodiazepines in
      decreasing fear-related behavior. However, no research has yet been published
      regarding the effects of micro-infusions of benzodiazepines, or any other GABA-A
      receptor agonist, into the MPFC. In addition, previous work has suggested that
      there may be functional differences between the dorsal and ventral subregions of
      the MPFC in regard to fear and anxiety. Therefore, the present study examined the
      effects of dorsal and ventral MPFC infusions of the benzodiazepine midazolam in
      two well-validated animal models of anxiety, the elevated plus maze and the shock
      probe burying test. The results showed that bilateral (5 microg/side) infusions
      of midazolam into the MPFC produced anxiolytic effects in both behavioural tests,
      without affecting general activity or pain sensitivity. Furthermore, these
      anxiolytic effects were found in both the dorsal and ventral regions of the MPFC.
      The present findings indicate that the benzodiazepine receptors of the MPFC are
      capable of modulating fear-related behaviors.

PMID- 14670629
TI  - Effects of ZD6169, a K ATP channel opener, on neurally-mediated plasma
      extravasation in the rat urinary bladder induced by chemical or electrical
      stimulation of nerves.
AB  - The effects of oral administration of ZD6169, a potassium channel opener, on
      neurally mediated plasma extravasation in the urinary bladder and urethra were
      examined in urethane-anesthetized rats. Plasma extravasation was evaluated by
      measuring the tissue concentration of Evans blue, administered intravenously (50
      mg/kg) 15 min prior to removal of tissues. Plasma extravasation was induced by
      three different stimuli: intravesical administration of either 0.25% acetic acid
      or 100 microM capsaicin or electrical stimulation of the pelvic nerve on one side
      (50 V, 10 s trains, 30 Hz intra-train frequency at 1 min intervals for 40 min).
      ZD6169 (5 mg/kg), administered orally 5 h prior to stimulation, significantly
      reduced the capsaicin-induced (50% decrease, p<0.05) or the electrical
      stimulation-induced (58% decrease, p<0.05) plasma extravasation in the bladder,
      but did not prevent the plasma extravasation in the bladder or urethra induced by
      intravesical infusion of 0.25% acetic acid. Administration of a K(ATP) channel
      blocker, glibenclamide (20 mg/kg, iv) 45 min prior to ZD6169 administration
      blocked the effects of ZD6169 on the electrical stimulation-induced plasma
      extravasation in the bladder and reduced the effects of ZD6169 on capsaicin
      induced plasma extravasation. These findings indicate that ZD6169 (and/or a
      metabolite) can reduce neurogenic plasma extravasation in the bladder and are
      consistent with other studies indicating that ZD6169 can activate K(ATP) channels
      in C-fiber bladder afferents and suppress afferent activity.

PMID- 14670630
TI  - Glucose/oxygen deprivation induces the alteration of synapsin I and
      phosphosynapsin.
AB  - Synapsin I is believed to be involved in regulating neurotransmitter release and
      in synapse formation. Its interactions with the actin filaments and synaptic
      vesicles are regulated by phosphorylation. Because exocytosis and synapsin I
      phosphorylation are a Ca(2+)-dependent process, it is possible that an ischemic
      insult modifies the presynaptic proteins. However, the neuronal damage and the
      changes in synapsin I as well as its phosphorylation level as a result of
      glucose/oxygen deprivation (GOD) and reperfusion in organotypic hippocampal slice
      cultures have not been established. In this study, the level of synapsin I and
      phosphosynapsin was measured in organotypic hippocampal slice cultures in order
      to determine the role of synapsin I in the presynaptic nerve terminals during
      GOD/reperfusion. Propidium iodide fluorescence was observed in the CA1 area after
      GOD for 30 min, which could be detected in the whole pyramidal cell layer during
      reperfusion for 24 h. The immunofluorescence of the neuron specific nuclear
      protein, NeuN, showed a negative correlation with the PI fluorescence. During
      GOD/reperfusion, the immunofluorescence of synapsin I increased in the stratum
      radiatum and the stratum oriens of the CA1 area and the stratum lucidum and the
      stratum oriens of the CA3 area. The phosphosynapsin level evidently increased in
      the stratum lucidum of the CA3 area after GOD for 30 min, which was reduced to
      the control level after reperfusion. These results suggested that the neuronal
      damage and degenerations were observed as a result of GOD/reperfusion and the
      increase in synapsin I and its phosphorylation might play a role in modulating
      the release of neurotransmitters via exocytosis and in the formation of new
      synapses after brain ischemia.

PMID- 14670631
TI  - Inhibition of MEK/ERK 1/2 pathway reduces pro-inflammatory cytokine interleukin-1
      expression in focal cerebral ischemia.
AB  - It has been proposed that mitogen-activated protein kinase (MAPK) pathways may
      play a role in the regulation of pro-inflammatory cytokines, such as interlukine
      1, during cerebral ischemia. Our previous study showed that extracellular-signal
      regulated kinases 1 and 2 (ERK 1/2) were activated during focal cerebral ischemia
      in mice [J. Cereb. Blood Flow Metab. 20 (2000) 1320]. However, the effect of ERK
      1/2 activation in focal cerebral ischemia is still unclear. In this study we
      reported that in vivo phospho-ERK 1/2 expression increased following 30 min of
      middle cerebral artery occlusion (MCAO) in the mouse brain in both the ischemic
      core and perifocal regions. Western blot analysis and immunohistochemistry
      demonstrated that pro-treatment with 1,4-diamino-2,3-dicyano-1,4-bis butadiene
      (U0126) [J. Biol. Chem. 273 (1998) 18623] could significantly inhibit mouse brain
      phospho-MEK 1/2 and phospho-ERK 1/2 expression after 1-2 h of MCAO (p<0.05).
      Compared to the control group of mice, brain infarct volume was significantly
      decreased after 24 h of MCAO in the U0126-treated mice (27+/-6 vs. 46+/-9 mm(2),
      p<0.05). Inhibition of the MEK/ERK 1/2 pathway also prevented downstream kinase
      Elk-1 phosphorylation, and further reduced cytokine IL-1beta mRNA, but not
      TNFalpha, IL-1alpha, or chemokine MIP-1alpha mRNA expression. Our data
      demonstrates that in vivo the close linking of MEK 1/2, ERK 1/2, Elk-1, and IL-1
      mRNA expression in the cerebral ischemia animals suggests that ERK 1/2 pathway
      activation is important in pro-inflammatory cytokine IL-1beta signaling, which
      induces an inflammatory response and exacerbates ischemic brain injury.
      Inhibiting the ERK 1/2 pathway may therefore provide a novel approach for the
      reduction of ischemia-induced IL-1beta overexpression.

PMID- 14670632
TI  - Post-ischemic hypothermia-induced tissue protection and diminished apoptosis
      after neonatal cerebral hypoxia-ischemia.
AB  - Hypothermia is possibly the single most effective method of neuroprotection
      developed to date. However, the mechanisms are not completely understood. The aim
      of this study was to investigate the effects of post-ischemic hypothermia on
      brain injury and apoptotic neuronal cell death as well as related biochemical
      changes after neonatal hypoxia-ischemia (HI). Seven-day-old rats were subjected
      to left common carotid artery ligation and hypoxia (7.8%) for 1 h. Systemic
      hypothermia was induced immediately after hypoxia-ischemia, and body temperature
      was maintained at 30 degrees C for 10 h. The normothermic group was kept at 36
      degrees C. Brain infarct volumes and neuronal loss in the CA1 area of the
      hippocampus were significantly reduced at 72 h post-HI in the hypothermia group.
      Cytochrome c release and activation of caspase-3 and -2 at 24 h post-HI were
      significantly diminished by hypothermia. The numbers of cytochrome c- and TUNEL
      positive cells in the cortex and dentate gyrus of the hippocampus were
      significantly reduced in the hypothermia group compared with the normothermia
      group at 72 h post-HI. These results indicate that hypothermia may, at least
      partially, act through inhibition of the intrinsic pathway of caspase activation
      in the neonatal brain, thereby preventing apoptotic cell death.

PMID- 14670633
TI  - Rifampicin attenuates brain damage in focal ischemia.
AB  - Rifampicin is an antibacterial agent that is widely used in tuberculosis and
      leprosy therapy. Interestingly, some experimental studies indicate that
      rifampicin acts as a hydroxyl radical scavenger and a glucocorticoid receptor
      activator. In this study, the neuroprotective effect of rifampicin was evaluated
      after transient and permanent focal cerebral ischemia. Anaesthetized male
      C57BL/6j mice were submitted to permanent or transient thread occlusion of the
      middle cerebral artery (MCA). Reperfusion in transient ischemia was initiated 30
      min later by thread retraction. Rifampicin or vehicle were applied
      intraperitoneally before permanent or immediately after 30 min of transient
      ischemia. Later, 24 h after permanent or transient ischemia, animals were re
      anesthetized and decapitated. Brain injury was evaluated by triphenyltetrazolium
      chloride staining (TTC), terminal transferase biotinylated-dUTP nick end labeling
      (TUNEL) and cresyl violet staining. A 20-mg/kg sample of rifampicin showed a
      significant neuroprotection after cerebral ischemia. The number of TUNEL-positive
      cells in the striatum, where disseminated tissue injury was observed, was also
      reduced by application of rifampicin as compared with vehicle-treated animals.
      The present report shows that administration of rifampicin efficiently reduces
      brain injury after permanent and transient focal cerebral ischemia in mice.

PMID- 14670634
TI  - Heterogeneous co-localization of AT 1A receptor and Fos protein in forebrain
      neuronal populations responding to acute hydromineral deficit.
AB  - The present study investigates co-localization of AT(1A) receptor subtype and Fos
      protein in neuronal populations of the lamina terminalis (LT) that have been
      recruited during acute Na(+) and water depletion mediated by furosemide
      injections. For that purpose, we combined high cellular resolution of in situ
      hybridization technique to reveal neurons expressing AT(1A) receptor gene (AT(1A)
      mRNA) with the specificity of Fos protein immunoreactivity as a marker of
      neuronal activation (Fos-ir). As expected, furosemide treatment dramatically
      increased the density of Fos-immunoreactive neuronal population in all the
      regions of the LT compared to control (saline-injected animals). Distribution
      analysis of Fos-ir neurons and AT(1A) receptor-expressing neurons performed
      consecutively to furosemide-induced Na(+) and water depletion indicated that
      double-labeled neurons (AT(1A) mRNA+Fos-ir) represented the majority (67%) of the
      neuronal population that expressed AT(1A) receptor in the rim of the vascular
      organ of the lamina terminalis (OVLT). Double-labeled neurons amounted about 60%
      of the neurons that expressed AT(1A) receptor in the core of the subfornical
      organ (SFO) and 34% in the periphery of the SFO. In the median preoptic nucleus
      (MnPO), the density of the double-labeled neuronal population observed in the
      furosemide-treated animals remained weak compared to the control group of
      animals. Double-labeled neuronal population estimated in the MnPO of the
      furosemide-treated group of animals represented 17% of the neurons that express
      AT(1A) receptor gene. Our results report a heterogeneous distribution of the
      neuronal populations that co-localize AT(1A) receptor and Fos protein in the
      lamina terminalis after an acute Na(+) and water depletion. This study gives
      anatomical support to a direct action of endogenous AngII on c-fos transcription
      via binding on AT(1A) receptor in specific areas of the circumventricular organs
      (rim of the OVLT and core of the SFO). In the MnPO, our data indicate that
      intracellular signaling pathways unlikely couple AT(1A) receptor with c-fos
      transcription. The expression of Fos protein in this nucleus might be therefore
      secondary to the recruitment of excitatory inputs different from AngII. This
      observation underlines the complexity of molecules and neurocircuits in the
      preoptic region that are involved in the control of acute Na(+) and water
      deficit.

PMID- 14670635
TI  - Protein synthesis is necessary for dendritic spine proliferation in adult brain
      slices.
AB  - Dendritic spines, small protrusions from dendritic shafts, receive most of the
      excitatory synapses in cortical regions. Spines are highly plastic structures
      that can be rapidly produced or lost in response to a wide array of internal and
      external stimuli, and they proliferate in acute slice preparations [J. Neurosci.
      19 (1999) 2876]. The goal of the present study was to determine if protein
      synthesis is necessary for this spine proliferation. We found that the addition
      of protein synthesis inhibitors to acute slices (in which spines otherwise
      proliferate) blocked new spine growth. Furthermore, a population of longer spines
      was observed after 2 h but these did not develop during protein synthesis
      blockade. These data suggest that protein synthesis is necessary for new spine
      growth in acute brain slice preparations and support literature suggesting that
      newly produced spines develop from filopodia-like protrusions.

PMID- 14670636
TI  - Neuropeptide-containing neurons in the endopiriform region of the rat: morphology
      and colocalization with calcium-binding proteins and nitric oxide synthase.
AB  - The endopiriform nucleus, further divided into dorsal and ventral parts, and the
      neighbouring pre-endopiriform (pEn) nucleus form a region of highly heterogeneous
      structure involved in numerous physiological and pathological processes.
      Nonpyramidal neurons of this region containing three neuropeptides-somatostatin
      (SOM), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP)-were
      examined in this study. Their colocalization with three calcium-binding proteins
      parvalbumin (PV), calbindin D28k (CB), calretinin (CR), and with nitric oxide
      synthase (NOS), was investigated by qualitative and quantitative methods. The
      results are summarized as follows: (1) all studied substances are distributed in
      neurons of the entire region, (2) SOM-ir neurons constitute the most numerous
      neuropeptide-containing population, whereas NOS-ir neurons make up the largest
      population of all studied, (3) colocalizations are found in the endopiriform
      region (Enr) (SOM with CB, PV and NOS; VIP with CR; NPY with NOS and NOS with
      CR), (4) heterogeneity of the endopiriform region appears in the differences of
      cells' shape distributions of single-labeled (SOM-, CR-PV-ir) and double-labeled
      (SOM/CB-, SOM/PV-, NPY/NOS- and NOS/CR-ir) neurons, as well as in differentiated
      percentage values of SOM/NOS, NPY/NOS and VIP/CR double-labeled neurons in three
      studied parts; additionally, differences in distribution of immunoreactive
      neuropil elements between parts of the region are observed. Numerous regional
      differences concerning neuronal morphology and immunocytochemical characteristics
      justify further division of the endopiriform region into distinguished parts.
      Some immunocytochemical features of the neurons in studied region may contribute
      to the role in epileptogenesis.

PMID- 14670637
TI  - Effects of naloxone on the long-term potentiation of EPSPs from the pathway of
      Schaffer collateral to CA1 region of hippocampus in aged rats with declined
      memory.
AB  - Morris water maze (MWM) was employed to distinguish the aged rats with declined
      memory to investigate the effect of naloxone on the synaptic plasticity of
      hippocampus in declined memory aged rats. After administration with naloxone for
      7 days, LTP of excitatory post-synaptic potentials (EPSPs) from Schaffer
      collateral to CA1 region was recorded. The results showed that the maintenance of
      LTP of EPSPs from Schaffer collateral to CA1 subfield in isolate hippocampal
      brain slice was prolonged by naloxone with improved Morris water maze performance
      and reduced threshold of EPSPs. It is suggested that naloxone can improve
      learning and memory through enhancement of the synaptic plasticity of hippocampus
      in aged rats with declined memory.

PMID- 14670638
TI  - Allosteric modulation of [3H]dizocilpine binding to N-methyl-D-aspartate receptor
      by an endogenous Na+, K+-ATPase inhibitor: dependence on receptor activation.
AB  - An endogenous Na(+), K(+)-ATPase inhibitor, termed endobain E, has been isolated
      from rat brain and proved to decrease [3H]dizocilpine binding to cerebral cortex
      N-methyl-D-aspartate (NMDA) receptor, an effect independent of sodium pump
      activity. The purpose of this study was to disclose the mechanism of
      [3H]dizocilpine binding reduction by endobain E by performing saturation, kinetic
      and competitive assays. In saturation binding assays, endobain E increased K(d)
      without modifying B(max) value. To determine whether competitive or allosteric
      interaction was involved, kinetics of [3H]dizocilpine binding to cerebral cortex
      membranes was studied. Endobain E increased [3H]dizocilpine dissociation rate
      constant and induced an initial fast phase, without modifying association rate
      constant, indicating an allosteric interaction. In competitive [3H]dizocilpine
      binding assays, no additive effect was observed with endobain E plus competitive
      antagonists for glutamate or glycine sites (2-amino-5-phosphonopentanoic acid (AP
      5) and 7-chlorokynurenic acid, respectively), indicating that coagonist site
      blockade interferes with endobain E effect. However, the higher glutamate and
      glycine concentration, the greater its effect. Endobain E binding reduction was
      partially additive with that induced by ketamine or Mg(2+) (receptor-associated
      channel blockers). Results suggest that the greater the channel activation by
      glutamate and glycine, the greater endobain E allosteric effect. Furthermore, as
      ketamine and Mg(2+) interfere with endobain E effect, this factor most likely
      binds to the inner surface of the NMDA associated channel.

PMID- 14670639
TI  - Projections from the parabrachial nucleus to the vestibular nuclei: potential
      substrates for autonomic and limbic influences on vestibular responses.
AB  - Previous anatomical studies in rabbits and rats have shown that the superior
      vestibular nucleus (SVN), medial vestibular nucleus (MVN) and inferior vestibular
      nucleus (IVN) project to the parabrachial nucleus (PBN) and Kolliker-Fuse (KF)
      nucleus. Adult male albino rabbits and Long-Evans rats received iontophoretic
      injections of biotinylated dextran amine, Phaseolus vulgaris leucoagglutinin,
      Fluoro-Gold or tetramethylrhodamine dextran amine into either the vestibular
      nuclei or the PBN and KF nuclei. The results were similar in both rats and
      rabbits. Injections of retrograde tracers into the vestibular nuclei produced
      retrogradely labeled neurons bilaterally in caudal third of the medial, external
      medial, and external lateral PBN in both species, with more variable labeling in
      KF. Rats also had consistent bilateral (predominantly contralateral) labeling in
      the ventrolateral PBN. The most prominent labeling was produced from injections
      that included the SVN, with fewer labeled neurons observed from injections in the
      caudal MVN and the IVN. Anterograde transport of BDA from injections into the PBN
      and KF nuclei of rabbits revealed prominent projections to the SVN, dorsal aspect
      of the rostral MVN, caudal MVN, pars beta of the LVN and IVN. These connections
      appear to contain a component that is reciprocal to the vestibulo-parabrachial
      pathway and a non-reciprocal component to regions connected with the
      vestibulocerebellum and vestibulo-motor reflex pathways. These connections
      support the concept that a synthesis of autonomic, vestibular and limbic
      information is an integral property of pathways related to balance control in
      both the brain stem and forebrain. It is suggested that these projections may
      contribute broadly to both performance tradeoffs in vestibular-related pathways
      during variations in the behavioral context and affective state and the close
      association between anxiety and balance function.

PMID- 14670640
TI  - Differential effects of progestins. European Progestin Club.

PMID- 14670641
TI  - Classification and pharmacology of progestins.
AB  - Besides the natural progestin, progesterone, there are different classes of
      progestins, such as retroprogesterone (i.e. dydrogesterone), progesterone
      derivatives (i.e. medrogestone) 17alpha-hydroxyprogesterone derivatives (i.e.
      chlormadinone acetate, cyproterone acetate, medroxyprogesterone acetate,
      megestrol acetate), 19-norprogesterone derivatives (i.e. nomegestrol,
      promegestone, trimegestone, nesterone), 19-nortestosterone derivatives
      norethisterone (NET), lynestrenol, levonorgestrel, desogestrel, gestodene,
      norgestimate, dienogest) and spironolactone derivatives (i.e. drospirenone). Some
      of the synthetic progestins are prodrugs, which need to be metabolized to become
      active compounds. Besides the progestogenic effect, which is in common for all
      progestins, there is a wide range of biological effects, which are different for
      the various progestins and have to be taken into account, when medical treatment
      is considered.

PMID- 14670642
TI  - Metabolic and vascular effect of progestins in post-menopausal women.
      Implications for cardioprotection.
AB  - Estrogen therapy causes changes in a variety of cardiovascular risk factors,
      including insulin resistance, lipoprotein profile, haemostasis, coronary
      atherosclerosis and vascular reactive, that suggest a potential cardioprotective
      effect in postmenopausal women. With respect to the role of adjunctive
      progestins, currently available data suggest that the cardiovascular effects may
      differ depending on the type, dosage and route of administration of the
      progestin. Androgenic progestins antagonise the favourable cardiovascular effect
      of estrogens, whilst non-androgenic progestins do not impair, or may even
      enhance, the beneficial effect of estrogens. Therefore, less androgenic
      progestins would appear to be the agent of choice for combined hormone therapy in
      postmenopausal women with cardiovascular risk factors.

PMID- 14670643
TI  - Differential effects of progestins on hemostasis.
AB  - Recently large, prospective, randomized studies on hormone replacement therapy
      (HRT) have indicated that the progestin use might interfere with hemostasis and
      thus increase venous thrombotic events. Therefore, available publications were
      evaluated to determine whether progestins interfere with hemostasis, either when
      given alone via oral or parenteral routes or in combination with ethinylestradiol
      as synthetic estrogen or natural estrogens. There are indications that such
      interference is dependent upon the type and dose of the progestin, the route of
      application, the length of treatment and the type and dose of the estrogen with
      which it is combined. For natural progesterone, no negative effects on the
      hemostatic system were seen with either oral or parenteral application, in cyclic
      or continuous regimens, for the doses investigated. Similarly, no unwanted
      effects were seen with progestin only pills (POP), independent of the type and
      dose of progestin, or parenteral progestins. With the high-dose progestins used
      in gynaecological oncology, the increased activation of the hemostatic system
      resulting from the disease itself has to be taken into account when looking at
      any increased incidence of thromboembolic events in these patients. For
      estrogen/progestin combinations, the risk of venous thromboembolism is attributed
      to the estrogen used. Recent studies showed an increased rate of thromboembolic
      events in association with desogestrel-and gestodene-containing oral
      contraceptives, compared with those containing levonorgestrel. With HRT, a
      decrease in antithrombin factors could explain the increased rate of venous
      thrombotic events. In conclusion, progestins seems to have different effects on
      the hemostatic system due to their different pattern of biological activities.
      This was also shown in the arterial vascular system, where some progestins may
      reduce the endothelium-dependent vasodilating action of estrogens and stimulate
      intima proliferation and upregulate thrombin receptor expression while other
      progestins did not.

PMID- 14670644
TI  - Differential effects of progestins on the circulating IGF-I system.
AB  - OBJECTIVE: Circulating insulin-like growth factor-I (IGF-I) is mainly produced by
      the liver under GH stimulation and is influenced by nutrition and insulin. IGF-I
      bioavailability is regulated by interactions with specific binding proteins
      (IGFBPs). The objective of this paper is to review available data on
      modifications of the IGF-I system in menopausal women during HRT, with particular
      attention on the differential effects of progestins. METHOD: All available
      reports on the effects of different forms of HRT have been taken into account.
      RESULTS: Available data suggest that different kinds of HRT have different effect
      on the IGF-I system, depending on route of administration, oestrogen dose, basal
      IGF-I values and type of progestin. Oestrogen administration (oestrogen
      replacement therapy (ERT)) reduces circulating IGF-I mainly through a
      hepatocellular effect. The decrease is sharper when oral ERT is used (first pass
      hepatic effect) and in women with higher basal IGF-I levels. The progestins
      endowed with androgenic effects--the 19-nortestosterone derivatives and, to a
      lesser extent, medroxyprogesterone acetate (MPA)--tend to reverse the IGF-I
      decrease induced by oral oestrogens. In contrast, progestins devoid of androgen
      like hepatocellular and metabolic actions (e.g. dydrogesterone) do not interfere
      with the IGF-I decrease induced by oral oestrogens. Data on the effect of ERT on
      IGFBP-3 level are not consistent. Oral ERT, via hepatocellular actions (amplified
      by the first pass hepatic effect) causes a two to three-fold increase in IGFBP-1
      levels. Androgenic progestins oppose the IGFBP-1 increase induced by oral
      oestrogens. Data on the effect of ERT and different progestins on the level of
      free IGF-I are scant and inconsistent. CONCLUSION: Even if some aspects need
      clarification, available data demonstrate that different progestins have
      differential effects on the circulating IGF-I system.

PMID- 14670645
TI  - Differential effects of progestins on breast tissue enzymes.
AB  - There is substantial evidence that mammary cancer tissue contains all the enzymes
      responsible for the local biosynthesis of estradiol (E2) from circulating
      precursors. Two principal pathways are implicated in the final steps of E2
      formation in breast cancer tissue: the 'aromatase pathway' that transforms
      androgens into estrogens and the 'sulfatase pathway' that converts estrone
      sulfate (E1S) into estrone (E1) via estrone sulfatase. The final step is the
      conversion of weak E1 to potent biologically active E2 via reductive 17beta
      hydroxysteroid dehydrogenase type 1 activity. It is also well established that
      steroid sulfotransferases, which convert estrogens into their sulfates, are
      present in breast cancer tissues. One of the possible means of blocking E2
      effects in breast cancer is to use anti-estrogens, which act by binding to the
      estrogen receptor (ER). Another option is to block E2 using anti-enzymes (anti
      sulfatase, anti-aromatase, or anti-17beta-hydroxysteroid dehydrogenase (17beta
      HSD). Various progestins (e.g. promegestone, nomegestrol acetate, medrogestone,
      17-deacetyl norgestimate, dydrogesterone and its 20-dihydro derivative), as well
      as tibolone and its metabolites, have been shown to inhibit estrone sulfatase and
      17beta-hydroxysteroid dehydrogenase. Some progestins and tibolone can also
      stimulate sulfotransferase activity. These various progestins may therefore
      provide a new option for the treatment of breast cancer.

PMID- 14670646
TI  - Differential effects of progestogens on breast cancer cell lines.
AB  - Our in vitro results indicate that not all progestogens act equally on breast
      cancer cells. Some progestogens (medroxyprogesterone acetate (MPA),
      norethisterone acetate (NETA) and dienogest) alone or combined with estradiol
      (E2) stimulate proliferation of breast cancer cells, while others
      (dihydrodydrogesterone (DHD), the active metabolite of dydrogesterone, tibolone
      and progesterone (Prog)) alone or combined with estradiol induce apoptosis.
      Further pharmacological and clinical studies should be initiated to evaluate
      these findings in vivo.

PMID- 14670647
TI  - Progestins and their effects on the breast.
AB  - Nowadays, when the available scientific data on the in vivo effects of progestins
      on mammary gland tissue remain controversial, it is of utmost importance to
      establish adequate criteria to evaluate their actions. One of the reasons for
      this situation is that a variety of progestins have been studied using a number
      of different study designs. In addition, data relating to the effects of
      progestins on breast tissue have been interpreted differently from country to
      country. Recent data indicate that some progestins clearly oppose the favourable
      effects of estrogens on a number of important metabolic processes, e.g.
      influencing insulin-like-growth-factor (IGF)-1 serum levels. IGF-1 is a mitogenic
      and antiapoptotic peptide involved in growth regulation of breast epithelial
      cells. Circulating IGF-1 exerts endocrine action, it regulates growth hormone
      secretion by a negative feedback mechanism. In the past few years, both
      laboratory investigations and epidemiologic studies provided strong evidence that
      the IGF-1/growth hormone axis is involved in human cancer risk [Maturitas 29
      (1998) 61; Horm. Res. 51 (1999) 34; Eur. J. Cancer 36 (2000) 1224; Maturitas 41
      (2002) 299] Some progestins also have effects on the enzymes in breast tissue
      that are responsible for the local synthesis of estradiol. Thus, whilst
      progestins without androgenic action have been found to markedly inhibit these
      enzymes, an equivalent degree of inhibition is not achieved with testosterone
      derivatives. Therefore, special attention should be paid to the various partial
      actions of the different progestins and their effects on breast tissue.
      Furthermore, factors such as the duration of breast tissue exposure to progestin
      activity, the influence of different regimens on protective apoptotic mechanisms
      in the breasts, as well as dose levels and the degree of mammary gland tissue
      differentiation throughout treatment, should also be considered.

PMID- 14670648
TI  - Differential effects of progestins on the brain.
AB  - Interactions exist between progestins and the gamma-aminobutyric acid (GABA)
      receptor subtype A where C(21)-steroids function as activators. Other
      interactions between progesterone and neurotransmitter systems include
      stimulation of dopamine release in striatal tissue, stimulation of GnRH release
      from hypothalamic neurons and inhibition of opioid receptor binding and
      activation. Cyproterone acetate increases dopaminergic responses and binds to
      opiate receptors independently of its classical effect on the androgen receptor.
      Progesterone substitution in perimenopausal women promotes length and quality of
      sleep. This effect seems most prominent for progesterone administered vaginally.
      Progestins also play a role in the pathogenesis of migraine. Migraine symptoms
      occur predominantly during the perimenstrual stage. Women who suffer from
      menstrual migraine triggered by premenstrual progesterone loss often benefit from
      cyclic progesterone administration. This may be because progesterone and
      allopregnenolone reduce meningeal release of substance P and inhibit the
      development of neurogenic oedema. Women whose migraine symptoms subside during
      pregnancy, however, benefit from intramuscular medroxyprogesterone acetate.
      Progesterone, generated from pregnenolone by Schwann cells, also enhances myelin
      synthesis. Myelination of axons is promoted when progesterone is added to
      cultures of rat dorsal root ganglia. No reliable data exist with respect to the
      effects of other progestins on demyelinating disease. Progestins promote the
      growth of meningioma as progesterone receptors predominate in meningioma tissue.
      Progesterone and synthetic progestins should therefore not be prescribed in these
      patients.

PMID- 14670649
TI  - Overview on the effects of progestins on bone.
AB  - In view of the fact that fractures are the clinically relevant events, risk
      factors for fractures are discussed first. Bone mineral density (BMD) appears to
      be a much less important risk factor for the most severe hip fractures than the
      risk of falling. No results of experimental studies on hormones and fractures at
      advanced age are available. An overview of the effects of progestins on bone is
      given. Effects of progestins on bone have been studied by in vitro experiments
      using cell lines and by more relevant clinical observations. Prospective studies
      have been conducted following the use of progestins contained in oral
      contraceptives, alone or in combination with oestrogens; long-term contraception
      by injection of depot preparations; so-called "add-back" hormonal therapy
      attempting to reverse the adverse effects of gonadotropin releasing hormone
      agonists on bone and after different regimens of hormone replacement therapy
      (HRT) in postmenopausal women. From the data there are no indications that the
      various progestins, used in clinical practice, have either a bone-protective or
      an oestrogen antagonistic activity. Progestins do not add or subtract much of the
      protective action of oestrogens on the bones.

PMID- 14670652
TI  - Injury, pseudoinjury, and litigation.

PMID- 14670660
TI  - Routine use of postoperative ICU care for elective craniotomy: a cost-benefit
      analysis.
AB  - OBJECTIVE: Postoperative monitoring in an intensive care unit (ICU) setting
      following elective craniotomy is routine at many institutions, as it is believed
      that this reduces the incidence and potential seriousness of early postoperative
      complications. This is unproven, however, and ICU resources are scarce and
      costly. At our institution, one surgeon began to routinely transfer elective
      craniotomy patients directly to the floor following an uneventful postanesthesia
      care unit (PACU) recovery. This study was undertaken to see whether that practice
      was safe and cost-effective. METHODS: A retrospective cohort of 430 consecutive,
      elective adult craniotomies, from February, 2000 to September, 2001 were
      analyzed. Variables were divided into 12 major groups: attending surgeon, age,
      sex, diagnosis, Current Procedural Terminology (CPT) code, length of stay,
      preoperative deficit, medical co-morbidities, postop floor, medical
      complications, neurological complications, and total hospitalization cost.
      RESULTS: Patients admitted to the surgical intensive care unit (SICU) did not
      have fewer complications than patients transferred directly to the floor.
      Patients admitted to the SICU did not have more preoperative neurological
      deficits or medical co-morbidities. Age was not a significant predictor of either
      medical or neurological complications. In patients without initial postop
      complications, only length of stay and postop floor assignment correlated with
      cost (p < 0.001). Immediate transfer to the floor decreased average
      hospitalization length by 3 days, and provided cost savings of $4,026 per
      patient. CONCLUSIONS: Selective, rather than routine use of postoperative ICU
      care in elective craniotomy patients is safe, resulting in no greater incidence
      of medical or neurological complications, and may provide significant reductions
      in average hospitalization length and cost.

PMID- 14670663
TI  - Stereotactic radiosurgery for brain metastases from gastrointestinal tract
      cancer.
AB  - BACKGROUND: Outcomes in patients with brain metastases from gastrointestinal
      tract cancers are not well defined. In this study we used precise, single
      session, focal tumor irradiation (radiosurgery) in patients with brain metastases
      and evaluated the results. METHODS: Thirty-nine patients had brain metastases
      from gastrointestinal tract cancer and were treated with radiosurgery. Thirty-two
      also had whole brain radiotherapy. Primary lesions included colorectal cancer (n
      = 25), esophageal cancer (n = 11), cholangiocarcinoma (n = 1), duodenal cancer (n
      = 1), and jejunal cancer (n = 1). Seventy-two tumors were treated. RESULTS: The
      overall median survival was 9 months after diagnosis of metastatic brain disease
      and 5 months after radiosurgery. The 1-year survival rate after radiosurgery was
      19%. The last imaging study of 49 tumors showed complete remission (CR) in 3
      tumors (6.1%), partial remission (PR) in 27 tumors (55.1%), no change (NC) in 11
      tumors (22.4%), and progression in 8 tumors (16.3%). The local tumor control rate
      (CR, PR, NC) was 84%. Two patients (5.1%) had a new or worsening neurologic
      deficit after radiosurgery. CONCLUSIONS: Stereotactic radiosurgery provides
      reasonable local control of brain metastases from gastrointestinal tract cancer
      with few side effects. However, it should be used judiciously in patients with
      active extracranial cancers since the expected survival may be limited.

PMID- 14670666
TI  - Investigation of the surgically treated and untreated unruptured cerebral
      aneurysms of the anterior circulation.
AB  - BACKGROUND: The natural history of unruptured cerebral aneurysms and the surgical
      risks are modified by several factors including size, location, and presence of
      subarachnoid hemorrhage (SAH). The main confusion arises because the backgrounds
      of the past reports describing the natural history or the surgical complication
      of unruptured cerebral aneurysms were different. The present study aimed to
      adjust the backgrounds and investigate the surgical indication with close
      monitoring of both surgically treated and untreated unruptured cerebral
      aneurysms. METHODS: In the past 9 years, 201 patients who had unruptured anterior
      circulation aneurysms were monitored. The decision of the operation was not
      randomized. The patients were divided into three subgroups by the size of the
      aneurysms (small group: below 5 mm, medium group: between 5 and 15 mm, large
      group: over 15 mm). In both surgically untreated and treated patients, overall
      mortality and morbidity corresponding to Rankin score II or worse was counted as
      unruptured aneurysm related event. The ratio of event free was compared between
      surgically treated and untreated patients using Log-rank test. RESULTS: In
      untreated patients, SAH was noted in 1 in the small group and 4 in the medium
      group. The annual rupture rate of the medium group was 12 times higher than that
      of the small group. In surgically treated patients, overall mortality and
      morbidity of the surgery was 2.3% in the small group, 3.6% in the medium group,
      and 20% in the large group. One surgically treated patient had SAH because of
      regrowth of aneurysm. When ratio of event free was compared, no significant
      advantage of surgery was noted in the small group and in all of the patients.
      However, the benefit of surgery was significant in the medium group (Log-rank p =
      0.0189). CONCLUSIONS: The present results indicated that prophylactic surgery has
      a benefit for the medium-size aneurysms (5-15 mm) of the anterior circulation.
      For large aneurysms, individual investigation is necessary because of the variety
      of surgical difficulties, and the complex symptoms because of rupture and the
      mass effect as well as cerebral embolism. In small aneurysms, careful observation
      may be a reasonable choice unless the aneurysm is at a specially high risk of
      rupture.

PMID- 14670669
TI  - Giant aneurysm of the azygos pericallosal artery: case report and review of the
      literature.
AB  - BACKGROUND: Pericallosal aneurysms are encountered less than 6.7%, and giant
      aneurysms among them even less. Giant azygos pericallosal artery aneurysm at the
      callosomarginal bifurcation is extremely rare, and our case presented herein is
      the second one. The case is discussed with thorough review of the literature.
      METHODS: A 65-year-old woman presented with an extremely rare giant aneurysm on
      the azygos pericallosal artery manifesting as subarachnoid hemorrhage in World
      Federation of Neurosurgical Societies Grade 3. Computed tomography (CT), magnetic
      resonance angiography (MRA), and four vessel angiography revealed a giant azygos
      pericallosal artery aneurysm associated with a second aneurysm at the left M1.
      RESULTS: After recovery to Grade 2, she underwent surgery via the right frontal
      interhemispheric approach for the azygos artery aneurysm on the 17th day after
      bleeding. The true dimensions of the aneurysm were greater than indicated by
      angiography because of partial thrombosis. Trilobulate aneurysm was carefully
      dissected from the surrounding structures. Postoperative cerebral angiography
      showed no filling of the clipped aneurysm and preservation of circulation.
      CONCLUSIONS: The treatment of distal anterior cerebral artery aneurysms is often
      difficult, because of their broad-based irregular configurations and adherence to
      surrounding tissue, tendency to bleed irrespective of size and the coexistence of
      other cerebral aneurysms. However, excellent outcomes can be obtained based on
      thorough preoperative radiologic evaluation, including magnetic resonance imaging
      (MRI), and correct selection of surgical approach.

PMID- 14670672
TI  - De novo distal posterior cerebral artery aneurysm.
AB  - BACKGROUND: De novo aneurysms in the posterior circulation are very rare. The
      authors describe a first case of ruptured de novo posterior cerebral artery (PCA)
      aneurysm in the P3 portion. CASE DESCRIPTION: A 52-year-old woman with ruptured
      de novo P3 aneurysm was treated by early endovascular obliteration using
      Guglielmi Detachable Coils (GDC). To prevent vasospasm, she received
      postoperative treatment with a hypertensive hypervolemia dilution and a calcium
      antagonist. She was discharged without neurologic deficits. CONCLUSIONS: Aneuryms
      arising from peripheral segment of PCA are rare, and delayed surgical clipping
      has been recommended for these lesions. This is the first report of a de novo P3
      ruptured aneurysm treated by endovascular embolization using GDC in the acute
      stage of subarachnoid hemorrhage. The characteristics of de novo posterior
      circulation aneurysms and the strategy for the distal PCA aneurysms are
      discussed.

PMID- 14670674
TI  - Ruptured aneurysm at the choroidal branch of the posterior inferior cerebellar
      artery: a case report and review of the literature.
AB  - BACKGROUND: The authors present a rare case of a ruptured aneurysm at the
      choroidal branch of the posterior inferior cerebellar artery (PICA). CASE
      DESCRIPTION: A 77-year-old female was admitted to our institute because of sudden
      onset of severe headache and vomiting. Radiologic examination revealed
      intraventricular hemorrhage caused by rupture of the aneurysm at the choroidal
      branch of the PICA. The fusiform aneurysm was resected after ligation via a
      midline suboccipital approach. CONCLUSIONS: The conclusions drawn from this
      experience and a review of the literature include the following: (1) the aneurysm
      at the branch of the PICA is frequently associated with anomalies of the vascular
      structure, particularly in hypoplasty of the contralateral PICA; (2) hemodynamic
      stress is speculated to be a causative factor of these lesions; (3) cases with
      hypoplasty of the contralateral PICA have the possibility of developing
      nonmycotic peripheral aneurysms at the branch of the PICA; (4) these aneurysms
      should be managed immediately because of the high risk of rebleeding.

PMID- 14670675
TI  - Successful brainstem cavernous malformation resection after repeated hemorrhages
      during pregnancy.
AB  - BACKGROUND: Pregnancy may be a risk factor for aggressive behavior in cavernous
      malformations. Relatively few cases exist in the literature and management is
      unclear. METHODS: This unique case report describes a 28-year-old female 27 weeks
      pregnant who presented with 2 hemorrhages from a pontine cavernous malformation
      within 1 week. Morbidity increased with the second hemorrhage. RESULTS: The
      patient underwent a suboccipital craniotomy and excision of the cavernous
      malformation. She successfully delivered a normal child at 36 weeks gestation and
      is ambulatory and independent 3 months postoperatively. CONCLUSIONS: Pregnancy
      and prior hemorrhage may be risk factors for repeated hemorrhages. Management
      decisions can be difficult during pregnancy, but successful excision during
      pregnancy is possible. The behavior of cavernous malformations and management
      decisions for this patient are discussed.

PMID- 14670677
TI  - Brain temperature and cerebral blood flow imaging in patients with severe
      subarachnoid hemorrhage: report of two cases.
AB  - BACKGROUND: Temperature reversal, which is defined as observation of higher brain
      temperature than systemic temperature followed by lower brain temperature than
      systemic temperature, implies a poor prognosis in patients with severe
      subarachnoid hemorrhage (SAH). Serial regional cerebral blood flow (CBF) imaging
      using single-photon emission tomography (SPECT) was performed in 2 patients with
      severe SAH who showed temperature reversal. CASE DESCRIPTION: 54-year-old woman
      and a 55-year-old man with severe SAH underwent ventricular drainage using a
      catheter that allowed monitoring of the brain temperature. SPECT imaging in these
      two patients showed that CBF was preserved before the occurrence of the
      temperature reversal and was exhausted afterwards. These patients died within 2
      to 3 days. CONCLUSIONS: Temperature reversal may indicate the exact time when
      absence of brain perfusion occurs, causing irreversible brain damage.

PMID- 14670679
TI  - De novo germinoma in the brain in association with Klinefelter's syndrome: case
      report and review of the literature.
AB  - BACKGROUND: There are no previous reports about de novo germ cell tumors without
      any past history of germ cell tumor. We describe a case of de novo cerebral
      germinoma in association with Klinefelter's syndrome. CASE DESCRIPTION: A boy had
      undergone growth hormone therapy for dwarfism because of hypopituitarism from 10
      to 17 years old. The result of karyotyping at the age of 13 was 47,XXY. Magnetic
      resonance images (MRI) of the brain at the age of 17 years showed no lesions. Two
      years later, at the age of 19, the patient noticed onset of mild right
      hemiparesis. MR imaging revealed the existence of a brain tumor in the left
      temporal lobe and hypothalamus. The patient underwent an operation and the
      histologic diagnosis of the lesion was germinoma. After postoperative
      chemotherapy and radiation therapy, the lesion disappeared and the patient was
      discharged uneventfully. CONCLUSIONS: To the best of the authors' knowledge, this
      is the first reported case of a germ cell tumor to be de novo without any past
      history of other germ cell tumor and the seventh case in which it occurred in
      association with Klinefelter's syndrome.

PMID- 14670681
TI  - The role of PCV chemotherapy in the treatment of central neurocytoma:
      illustration of a case and review of the literature.
AB  - BACKGROUND: Most central neurocytomas follow a benign clinical course. However,
      more aggressive variants have been described requiring additional surgical
      resection, radiation, or chemotherapy. Chemotherapy has rarely been used as an
      adjuvant therapy for central neurocytomas. METHODS: We report a case of a 20-year
      old girl who underwent four subtotal resections, over the course of 3 years, for
      a large central neurocytoma that continued to progress. She was not a candidate
      for stereotactic radiosurgery, given the large tumor size. To avoid radiation
      injury in a young patient, she was treated with six cycles of chemotherapy
      including procarbazine, CCNU, and vincristine. Procarbazine was stopped after 2
      cycles because of the development of a rash. Serial magnetic resonance imaging
      was used to follow treatment response. RESULTS: Her tumor started to decrease in
      size after 2 cycles of chemotherapy and continued to shrink until it stabilized
      after 5 cycles of chemotherapy. A small area of residual tumor with minimal
      enhancement persisted along the left lateral ventricle and remained stable for at
      least 16 months after the completion of chemotherapy. CONCLUSIONS: To our
      knowledge, this is only the fourth report describing the use of chemotherapy for
      progression of central neurocytomas as a treatment alternative to radiation
      therapy. The use of procarbazine, CCNU, and vincristine has not been previously
      described for the treatment of a central neurocytoma and presents an additional
      treatment option.

PMID- 14670682
TI  - Lipomatous medulloblastoma: a rare adult tumor variant with a uniquely favorable
      prognosis.
AB  - BACKGROUND: Lipomatous medulloblastoma is a rare but apparently distinct variant
      of medulloblastoma. There have been only 14 prior published cases. We report an
      additional case of an adult who presented with a multicentric form of this unique
      lesion. METHODS: A 45-year-old woman underwent magnetic resonance imaging for
      evaluation of progressive headaches, nausea/vomiting, vertigo, and ataxia.
      Multiple bilateral mass lesions in the posterior fossa were noted, along with
      obstructive hydrocephalus and significant mass effect. RESULTS: Via a right
      suboccipital and retrosigmoid craniotomy the largest cerebellar lesion was
      resected and a second lesion biopsied. The third mass on the contralateral side
      was not disturbed. Postoperatively the patient received fractionated radiotherapy
      to a dose of 54 Gy and chemotherapy with cisplatin, PCNU, and vincristine for 1
      year. She is alive without deficit, with a Karnofsky Performance Status of 100,
      and with no evidence of disease on neuroimaging 3 years after diagnosis.
      CONCLUSIONS: This distinct variant of medulloblastoma appears to occur in adults
      only and has a uniquely favorable prognosis, even with incomplete resection with
      institution of appropriate adjuvant therapies. Multicentricity does not imply a
      less favorable prognosis.

PMID- 14670683
TI  - Aneurysmal bone cyst of the temporal bone: case report.
AB  - BACKGROUND: Aneurysmal bone cysts (ABCs) are uncommon lesions of the temporal
      bone and their occurrence in the calvarium is rare. CASE DESCRIPTION: A case of a
      right temporal ABC is reported in a 14-year-old boy who presented swelling of the
      right temporal region. Magnetic resonance imaging showed a destructive and
      expansile bone lesion on the right anterior temporal and orbital bone. The lesion
      was removed in total by the right temporal craniotomy and orbitozygomatic
      osteotomy. ABC was diagnosed in the pathologic examination. The patient had good
      recovery during the postoperative course. CONCLUSIONS: This report presents the
      diagnosis and imaging of an ABC in the temporal bone. This localization is very
      rare for ABC. Total excision, if feasible, is the ideal treatment.

PMID- 14670684
TI  - Benign metastasizing leiomyoma causing spinal cord compression.
AB  - BACKGROUND: Leiomyoma as a cause of cord compression is extremely rare. To our
      knowledge this is the first report of a dural-based leiomyoma and second report
      of a leiomyoma causing cord compression. CASE DESCRIPTION: A 38-year-old female
      renal transplant recipient presented with features of cervical cord compression.
      On imaging and at surgery, the tumor was mistaken for a neurofibroma. A cervical
      laminectomy and near total excision of the tumor was done. She did well in the
      postoperative period but presented 5 months later with thoracic empyema leading
      to septicemia and her demise. Ultrasound examination and autopsy showed
      leiomyomas in many other sites including the uterus. CONCLUSIONS: The presence of
      extrauterine and uterine leiomyomas is a curious condition termed as "benign
      metastasizing leiomyoma." As our patient was on immunosuppressant therapy
      following a renal transplant, it might have predisposed her to this rare
      condition with multifocal tumors.

PMID- 14670686
TI  - Recurrent primary fibrosarcoma of the brain treated with the GliaSite
      brachytherapy system: case report.
AB  - BACKGROUND: Primary brain sarcomas are rarely curable with surgery and standard
      radiation therapy. They typically recur locally within 6 months of treatment.
      This case report describes a novel treatment approach for primary or recurrent
      brain sarcomas with intracavitary brachytherapy. CASE DESCRIPTION: This 34-year
      old female presented with a large and rapidly recurrent primary fibrosarcoma in
      the right fronto-parietal brain only 1 month postinitial total resection. She was
      reoperated, again with an MRI-documented gross total resection, but at this
      second surgery a GliaSite RTS (a recently FDA-approved balloon catheter system
      for intracranial intracavitary brachytherapy) was inserted into the surgical
      cavity. Over four days a radiation dose of 152 Gy was delivered at the balloon
      surface dose and 50.0Gy was delivered at a depth of 7 mm from balloon surface.
      The patient received subsequent treatment with external beam radiation and
      chemotherapy. The patient tolerated her treatment well and has shown no evidence
      of tumor recurrence with a follow up of 18 months. CONCLUSIONS: Boost
      intracavitary brachytherapy can play a critical role in preventing local
      recurrence and early death in patients with primary brain sarcomas.

PMID- 14670688
TI  - Words for neurosurgeons from the President of Portugal.

PMID- 14670689
TI  - Intravital microscopy for the study of mouse microcirculation in anti
      inflammatory drug research: focus on the mesentery and cremaster preparations.
AB  - Intravital microscopy is an extremely useful tool used as a qualitative and
      quantitative way of observing leukocyte-endothelial cell interactions in-vivo.
      This present article reviews the methods of the technique of intravital
      microscopy, in particular focussing on the mesentery and cremaster preparations.
      It focuses on how to actually carry out the experiments required to directly
      observe and localize the changes in the function of the microcirculation. Where
      necessary the reader is asked to refer to a selection of highly acclaimed
      publications, which should enable the reader to truly appreciate, and if
      necessary perform, the technique of intravital microscopy.

PMID- 14670690
TI  - Sensitivity and specificity of isolated perfused guinea pig heart to test for
      drug-induced lengthening of QTc.
AB  - INTRODUCTION: The purpose of this study was to determine the sensitivity and
      specificity for predicting the liability of a compound to lengthen QTc using
      isolated, perfused guinea pig hearts (Langendorff preparation). METHODS: QTc
      (Fridericia correction) was calculated from bipolar transventricular
      electrograms. Hearts were exposed to escalating concentrations of 26 compounds
      thought to lengthen, and 13 compounds thought not to lengthen, QTc in humans.
      RESULTS: In this preparation, QTc was found to lengthen in 26 of 26 compounds
      thought to be positive (sensitivity 1.00) and not to lengthen or to lengthen
      insignificantly in 13 of 13 compounds thought to be negative (specificity 1.0) in
      man. Probucol and ontazolast could not be studied because of limited solubility.
      Successful experiments were conducted on over 98% of guinea pigs anesthetized.
      DISCUSSION: We believe that the isolated perfused guinea pig heart is an in vitro
      preparation that could be utilized early in preclinical testing for identifying a
      liability to lengthen QTc in humans, but we do not believe--as is true also for
      other in vitro methods--that the concentration at which the liability is
      demonstrated in vitro necessarily predicts the concentration at which a liability
      exists in man.

PMID- 14670691
TI  - A method for evaluating drug effects on intermittent claudication using a
      treadmill in rats with unilateral hindlimb artery occlusion.
AB  - INTRODUCTION: We have developed an in vivo experimental model for evaluating
      peripheral arterial insufficiency and predicting the efficacy of drugs on
      intermittent claudication (IC). We found that rats that had been running normally
      on a treadmill developed a gait disturbance when a hindlimb artery was
      unilaterally occluded. We hypothesized that the distance run before gait
      disturbance developed (DGD) in rats with occlusion of a hindlimb artery might be
      an appropriate index of the severity of peripheral insufficiency, and that the
      model might serve as a test bed for evaluating drug efficacy. To prove this
      hypothesis, we examined whether DGD was determined by severity of hindlimb
      ischemia. Furthermore, we also examined whether cilostazol, which has been proved
      to have ameliorative effects in patients with IC, increased DGD. METHODS: To vary
      the severity of ischemia, either the superficial femoral artery, the distal
      portion of the iliac artery, or the proximal portion of iliac artery was
      unilaterally occluded. After a recovery period, these rats were subjected to a
      treadmill test (15 m/min and 15% incline) to determine DGD and examine the effect
      of cilostazol on DGD. RESULTS: DGD was the longest and shortest in rats with
      superficial femoral artery and proximal portion of iliac artery occlusion,
      respectively. Intermediate DGD was observed in rats with distal portion of iliac
      artery occlusion. These data suggest that DGD is correlated with the severity of
      hindlimb ischemia. Two weeks or longer administration of cilostazol 30 and 100
      mg/kg twice a day evoked a significant increase in DGD. DISCUSSION: Peripheral
      arterial insufficiency and its modulation by drugs can be evaluated in rats with
      unilateral hindlimb artery occlusion, on a treadmill, by measuring DGD.

PMID- 14670692
TI  - A method for determining whether hypotension caused by novel compounds in
      preclinical development results from histamine release.
AB  - INTRODUCTION: Many therapeutic agents stimulate histamine release from mast
      cells, which results in a decrease in blood pressure. The purpose of this study
      is to establish a method to determine if the mechanism of action, or one of the
      mechanisms, of hypotensive compounds is related to the release of histamine. The
      method was developed using a novel hypotensive compound, SC-372. METHODS: In
      Inactin anesthetized rats, after intravenous administration of SC-372 (0.3-7
      mg/kg), the 2 and 7 mg/kg resulted in a dose-dependent decrease in blood
      pressure. Histamine (0.1 and 1 mg/kg) was injected intravenously to establish
      whether histamine release was the mechanism of action for the hypotension induced
      by SC-372. Compound 48/80 (0.1 mg/kg, promotes histamine release) and Cromolyn (1
      mg/kg/min, [5 min], prevents histamine release from mast cells) were
      characterized and used intravenously in combination with/or compared to SC-372.
      RESULTS: Histamine resulted in a decrease in blood pressure that was unaffected
      by Cromolyn (1 mg/kg). Administration of Compound 48/80 resulted in a rapid
      reduction of systemic blood pressure. Intravenous infusion of Cromolyn prior to
      the injection of Compound 48/80 significantly attentuated the hypotensive
      response and the increase in histamine levels in the plasma. Intravenous
      administration of SC-372 resulted in a rapid reduction in blood pressure with a
      profile similar to that of Compound 48/80. When the rats were treated with
      Cromolyn prior to the administration of SC-372, both the blood pressure and
      plasma histamine levels were maintained at their pretreatment control levels.
      DISCUSSION: These data indicate that Compound 48/80 and Cromolyn can be used in
      rats to screen for histamine release-dependent drug-induced hypotension and
      suggest that the rapid decrease in blood pressure caused by SC-372 may result
      from histamine release from mast cells.

PMID- 14670693
TI  - The automated bioaerosol exposure system: preclinical platform development and a
      respiratory dosimetry application with nonhuman primates.
AB  - INTRODUCTION: Well-characterized inhalation exposure systems are critical for
      preclinical testing and pathogenesis studies. The automated bioaerosol exposure
      system (ABES) provides a microprocessor-driven inhalation platform that provides
      exquisite data acquisition and control over all aspects of inhalation exposures.
      Because this represents a new technology, the development and characteristics of
      the ABES are thoroughly discussed. In addition to control over homeostatic and
      aerosol conditions, the ABES incorporates a dosimetry function based on
      respiratory performance of the test animal during inhalation. METHODS: To test
      the system, rhesus macaques were initially sham-exposed using the ABES in a head
      only inhalation configuration. The ABES was subsequently used under biosafety
      level (BSL)-III conditions in a vaccine efficacy challenge using aerosolized
      staphylococcal enterotoxin B (SEB) toxin, again using the real-time dosimetry
      function of the system. RESULTS: Sham exposure results indicated significant
      departures from corresponding whole-body plethysmography (WBP) respiratory
      function estimates taken before the inhalation procedure. The results of the SEB
      exposure demonstrated the utility of using the ABES to generate consistently
      accurate and precise inhalation dose. DISCUSSION: Taken together, the results of
      the sham and toxin challenge experiments demonstrate that the dosimetry function
      of the ABES improves the precision and accuracy of inhaled dose delivery and
      calculation as compared to predictive WBP conducted before the exposure. The ABES
      represents a highly adaptable platform for the design of inhalation systems to
      suit the requirements of a variety of animal models.

PMID- 14670694
TI  - An automated blood sampler for simultaneous sampling of systemic blood and brain
      microdialysates for drug absorption, distribution, metabolism, and elimination
      studies.
AB  - INTRODUCTION: A major problem in preclinical drug development where blood
      sampling from small animals is a routine practice is the time and labor involved
      in the serial sampling of small blood volumes from small animals such as rats for
      the duration of pharmacokinetic/pharmacodynamic (PK/PD) studies. The traditional
      method of manually drawing blood from the animal requires the animal to be
      anesthetized or restrained with some device, both of which cause stress to the
      animal. METHODS: An automated blood sampler (ABS) was developed to simultaneously
      collect blood and brain microdialysate samples at preprogrammed time points from
      awake and freely moving animals. The samples are delivered to fraction collectors
      and stored at 4 degrees C until use. The lost blood volume during collection is
      replaced with sterile saline to prevent fluid loss from the animal. In addition,
      the system is capable of collecting urine and feces for metabolism studies and
      monitoring the animal activity for behavioral studies. In the present study,
      blood samples were collected for 24 h after dosing rats orally with a 5 mg/kg
      dose of olanzapine (OLAN). Brain dialysates were collected for the same duration
      from a microdialysis probe implanted in the striatum. RESULTS: The
      pharmacokinetic parameters, obtained after an oral dose, are in good agreement
      with reported values in literature. The pharmacodynamic information obtained from
      brain dialysates data show that OLAN elevates the concentration of dopamine (DA)
      in the brain and remains in the brain even after it is cleared from the plasma.
      DISCUSSION: The ABS described here is a very useful tool in drug development to
      accelerate the pace of preclinical in vivo studies and to simultaneously provide
      pharmacodynamic and physiological information.

PMID- 14670695
TI  - Calculating the hybrid (macro) rate constants of a three-compartment mamillary
      pharmacokinetic model from known micro-rate constants.
AB  - INTRODUCTION: While there are published equations for calculating the hybrid
      (macro) rates constants (lambda1 and lambda2) of a two-compartment mamillary
      pharmacokinetic model from its micro-rate constants (e.g., k12, k21 etc.), there
      appears to be no report of an analogous method for a three-compartment model. The
      hybrid rate constants are the exponents of the multi-exponential equation
      describing the time-course of the predicted blood concentrations. METHODS: Using
      the method of Wagner, the differential equations of a three-compartment model
      were solved by transformation into the Laplace domain then matrix manipulation.
      The inversion of the result back into the time domain requires finding the roots
      of a cubic polynomial. The equations of a convenient method for doing so are
      reported. This "analytical" method for finding the hybrid rate constants was
      compared with an alternative "simulation and fitting" method. For this, a model
      with known micro-rate constants was used to predict a time-course of blood
      concentrations for a bolus dose, which was then fitted to a tri-exponential
      equation to find the hybrid rate constants. RESULTS: The hybrid rate constants
      for the two methods were identical to at least four significant figures,
      confirming the validity of the analytical equations. DISCUSSION: The equations
      presented here fill a gap in the pharmacokinetic literature, which may be useful
      in some applications considering the widespread use of the three-compartment
      mamillary pharmacokinetic model.

PMID- 14670698
TI  - Acts of perceptual inquiry: problems for any stimulus-based simplicity theory.
AB  - Stimulus-specified simplicity is simply insufficient to predict the appearance of
      objects' 3D forms and figural shapes, etc., as originally intended. Which
      information a viewer chooses to attend can determine both what 3D structure is
      perceived and its attendant perceptual consequences; moreover, a shape's
      meaningfulness or denotivity [M.A. Peterson, Current Directions in Psychological
      Science 3 (1994) 105] can overcome simplicity-based figure-ground segregation. In
      both cases, perceptual consequences, such as subsequent perceived movements, are
      constrained or primed in ways that can help us corroborate and define what the
      viewer has perceived; that may help us in studying the underlying events in brain
      processing; and that should help in designing such perceptual applications as
      still and animated displays. Demonstrations, theoretical framework, and potential
      research tools are offered.

PMID- 14670699
TI  - Perceived complexity and the grouping effect in band patterns.
AB  - Symmetry properties have been shown to determine the perceived complexity of
      certain patterns. We used a paired-comparison method to obtain judgments of
      relative complexity for a family of two-dimensional regular patterns called band
      patterns. Although the complexity of these patterns is well predicted by their
      symmetry properties we were unable to explain an interaction observed between two
      of these properties for our experimental patterns. We discuss the implications of
      our results for two predominant approaches to the perceived complexity of
      patterns. Neither approach takes into account that the presence of grouping
      sometimes makes it difficult to perceive a relationship within the pattern that
      would--were it not for the grouping--simplify it. We conclude that grouping can
      mask simplicity and that this phenomenon is crucial to the understanding of
      perceived complexity.

PMID- 14670700
TI  - Contour grouping inside and outside of facial contexts.
AB  - We examine how contours group in isolation compared with when they are embedded
      in face-like contexts. As previously shown, contours that seem to group by
      phenomenological observation also show powerful effects on task performance: with
      contours that group, selective attention to one while ignoring another is poor
      (as indexed by Garner Interference (GI), but not Stroop Interference), whereas
      divided attention across contours is good. With contours that do not group,
      however, the reverse happens. Here we test pairs of curved lines (parentheses)
      displayed either in isolation or within contexts including cartoon faces, where
      these curves may serve as mouths or eyebrows. The results with isolated contours
      replicate previous findings of poor selective attention, but within face-like
      contexts the same contours showed nearly perfect selective attention (i.e., zero
      GI). Thus, contour grouping was weaker inside than outside of faces, a finding
      that contrasts with the widely-held belief that faces are processed configurally,
      not by local features.

PMID- 14670701
TI  - What does a compound letter tell the psychologist's mind?
AB  - The paradigm based on using compound stimuli for studying global and local
      processing is revisited. Noting that not all researchers employ compound stimuli
      for the same purpose, the issue of its purpose is discussed. It is argued that
      the paradigm is pertinent for examining at least three notions--formation
      preference, global addressability, and within-object global precedence. It is
      suggested that findings in the paradigm are accommodated well by a disjunction of
      those three perceptual dispositions. A number of further issues associated with
      the interpretation of findings obtained with it are examined as well. An
      experimental study is reported that is meant to examine one such issue--a
      possible artifact putatively introduced by the special attribute of element
      homogeneity characteristic of compound stimuli. Seven experiments were used to
      examine to what extent, if at all, global advantage observed in compound stimulus
      paradigms depends on element heterogeneity. Across those experiments,
      heterogeneity did not have any effect that could be interpreted as suggesting
      that the paradigm is biased in favor of the global structure due to element
      homogeneity.

PMID- 14670702
TI  - When does grouping happen?
AB  - Recent research on perceptual grouping is described with particular emphasis on
      identifying the level(s) at which grouping factors operate. Contrary to the
      classical view of grouping as an early, two-dimensional, image-based process,
      recent experimental results show that it is strongly influenced by phenomena
      related to perceptual constancy, such as binocular depth perception, lightness
      constancy, amodal completion, and illusory contours. These findings imply that at
      least some grouping processes operate at the level of phenomenal perception
      rather than at the level of the retinal image. Preliminary evidence is reported
      showing that grouping can affect perceptual constancy, suggesting that grouping
      processes must also operate at an early, preconstancy level. If so, grouping may
      be a ubiquitous, ongoing aspect of visual organization that occurs for each level
      of representation rather than as a single stage that can be definitively
      localized relative to other perceptual processes.

PMID- 14670703
TI  - The joint.
AB  - Some concave volumes are perceived as compositions of joined objects. Joined
      objects are optically undetermined, being compatible with three possible
      solutions: an empty intersection volume bounded by two indented objects; an
      intersection volume entirely filled-in by parts of two indented objects; a
      totally convex object joined to an indented object (the solution preferred by
      most perceivers). Knowledge of material penetrability does not predict 3D amodal
      completion. To identify relevant factors we selected different compositions and
      ran a multiple-regression analysis of completion choices. After eliminating
      colour, we considered six spatial factors: relative position along the vertical,
      relative size, orientation, proximity to the observer, minimization of completed
      parts, support relationship. The first two factors played a major role. The
      comparison of choices by upright versus inverted observers indicated that
      relative position along the vertical depends more on gravitational than
      egocentric coordinates. In conclusion, when relative spatial position and
      relative size cooperate, amodal completion of intersecting solids generates
      strong effects, which can overcome logical expectations.

PMID- 14670704
TI  - Representation and constraints: the inverse problem and the structure of visual
      space.
AB  - Visual space can be distinguished from physical space. The first is found in
      visual experience, while the second is defined independently of perception.
      Theorists have wondered about the relation between the two. Some investigators
      have concluded that visual space is non-Euclidean, and that it does not have a
      single metric structure. Here it is argued (1) that visual space exhibits
      contraction in all three dimensions with increasing distance from the observer,
      (2) that experienced features of this contraction (including the apparent
      convergence of lines in visual experience that are produced from physically
      parallel stimuli in ordinary viewing conditions) are not the same as would be the
      experience of a perspective projection onto a frontoparallel plane, and (3) that
      such contraction is consistent with size constancy. These properties of visual
      space are different from those that would be predicted if spatial perception
      resulted from the successful solution of the inverse problem. They are consistent
      with the notion that optical constraints have been internalized. More generally,
      they are also consistent with the notion that visual spatial structures bear a
      resemblance relation to physical spatial structures. This notion supports a type
      of representational relation that is distinct from mere causal correspondence.
      The reticence of some philosophers and psychologists to discuss the structure of
      phenomenal space is diagnosed in terms of the simple materialism and the
      functionalism of the 1970s and 1980s.

PMID- 14670705
TI  - Miracles of perception.
AB  - This paper draws a bird's eye view of various counter-intuitive characteristics
      of perception. Peculiar is that perception is a both tool and topic of its study.
      As a consequence, its output is easily mistaken for its input. Furthermore, its
      output is characterized by remarkable Gestalt features, such as mutual dependence
      of stimulus elements and detour solutions. Detour solutions require a complex
      perception process of testing countless optional pattern interpretations against
      a criterion. Likelihood is a plausible criterion for reasoning. For perception,
      however, the simplicity criterion is more appropriate. The consideration is that
      reasoning aims at establishing properties of distal objects whereas perception
      aims at establishing objects from proximal properties. The role of knowledge in
      perception seems plausible but often leads to conflicts. For instance, the
      assumption that knowledge about handedness is present in pattern representations
      conflicts with image mirror-image discrimination data. Moreover, knowledge does
      not provide an anchor for subjective time direction, but a Gestalt quality does.

PMID- 14670707
TI  - Structure of bacterial lipopolysaccharides.
AB  - Bacterial lipopolysaccharides are the major components of the outer surface of
      Gram-negative bacteria They are often of interest in medicine for their
      immunomodulatory properties. In small amounts they can be beneficial, but in
      larger amounts they may cause endotoxic shock. Although they share a common
      architecture, their structural details exert a strong influence on their
      activity. These molecules comprise: a lipid moiety, called lipid A, which is
      considered to be the endotoxic component, a glycosidic part consisting of a core
      of approximately 10 monosaccharides and, in "smooth-type" lipopolysaccharides, a
      third region, named O-chain, consisting of repetitive subunits of one to eight
      monosaccharides responsible for much of the immunospecificity of the bacterial
      cell.

PMID- 14670708
TI  - Structures of polysaccharides and oligosaccharides of some Gram-negative marine
      Proteobacteria.
AB  - The chemical structures of polysaccharides and LPS core oligosaccharides,
      isolated from various Gram-negative marine bacteria from the genera
      Pseudoalteromonas and Shewanella belonging to the Alteromonadaceae family and
      gamma-subclass of Proteobacteria, are reviewed. The polysaccharides are
      distinguished by the acidic character (e.g., due to the presence of hexuronic and
      aldulosonic acids and their derivatives) and the occurrence of unusual sugars,
      including N-acyl derivatives of 6-deoxyamino sugars, such as N-acetyl-D
      quinovosamine, N-acetyl-L-fucosamine and N-acetyl-6-deoxy-L-talosamine, and
      higher sugars like 2,6-dideoxy-2-acetamido-4-C-(3'-carboxamide-2',2'
      dihydroxypropyl)-D-galactopyranose (shewanellose). Many constituent sugars have
      various uncommon non-sugar substituents, such as alanine, formic, lactic and
      hydroxybutyric acids, sulfate, phosphate, and 2-aminopropane-1,3-diol.

PMID- 14670709
TI  - Characterisation of bacterial polysaccharides: steps towards single-molecular
      studies.
AB  - Techniques used in studies of polysaccharides, including chemical composition,
      linkage pattern, and higher order structures are in constant development. They
      provide information necessary for understanding of the polysaccharide properties
      and functions. Here, recent advancements in studies of the polysaccharides at the
      single-molecule level are highlighted. Over the last few years, single-molecule
      techniques such as force spectroscopy have improved in sensitivity and can today
      be used to detect forces in the pN range. In addition, these techniques can be
      used to investigate properties of single molecules close to physiological
      conditions. The challenges in the interpretation of the observations are aided by
      control experiments using well-characterised polysaccharides and by data provided
      by complementary methods. This field is expected to have increasing impact on the
      further advancement of the molecular understanding of the role of polysaccharides
      in various biological processes such as recognition and cell adhesion.

PMID- 14670710
TI  - Physicochemical properties of bacterial glycopolymers in relation to bioactivity.
AB  - An overview is given on the physicochemical properties of bacterial
      glycopolymers, i.e., pure oligo- and polysaccharides as well as glycolipids. Data
      from analysis of the chemical and physicochemical properties of various sugar
      polymers are summarized. Furthermore, data are presented on the thorough
      characterization of the most important class of bacterial glycopolymers, the
      lipopolysaccharides (LPS). These data comprise the chemical characterization, the
      gel to liquid crystalline phase transition behaviour of their acyl chains, the
      ultrastructural studies of their morphology, and the investigation of the types
      of aggregate structures present above the critical micellar concentration (CMC).
      Furthermore, the relevance of these data with respect to an understanding of the
      various biological effects elicited by LPS is discussed.

PMID- 14670711
TI  - Biosynthesis and assembly of Group 1 capsular polysaccharides in Escherichia coli
      and related extracellular polysaccharides in other bacteria.
AB  - Extracellular and capsular polysaccharides (EPSs and CPSs) are produced by a wide
      range of bacteria, including important pathogens of humans, livestock, and
      plants. These polymers are major surface antigens and serve a variety of roles in
      virulence, depending on the biology of the producing organism. In addition to
      their importance in disease, some EPSs also have industrial applications as
      gelling and emulsifying agents. An understanding of the processes involved in the
      synthesis and regulation of CPSs and EPSs therefore potentially contributes to an
      understanding of the disease state, surface expression of protective antigens,
      and modulation of polymer structure to give defined physical properties.
      Escherichia coli has provided important model systems for EPS and CPS
      biosynthesis. Here we describe current knowledge concerning assembly of the Group
      1 CPSs of E. coli and the conservation of similar mechanisms in other bacteria.

PMID- 14670712
TI  - Biosynthesis of O-antigens: genes and pathways involved in nucleotide sugar
      precursor synthesis and O-antigen assembly.
AB  - The O-antigen is an important component of the outer membrane of Gram-negative
      bacteria. It is a repeat unit polysaccharide and consists of a number of repeats
      of an oligosaccharide, the O-unit, which generally has between two and six sugar
      residues. O-Antigens are extremely variable, the variation lying in the nature,
      order and linkage of the different sugars within the polysaccharide. The genes
      involved in O-antigen biosynthesis are generally found on the chromosome as an O
      antigen gene cluster, and the structural variation of O-antigens is mirrored by
      genetic variation seen in these clusters. The genes within the cluster fall into
      three major groups. The first group is involved in nucleotide sugar biosynthesis.
      These genes are often found together in the cluster and have a high level of
      identity. The genes coding for a significant number of nucleotide sugar
      biosynthesis pathways have been identified and these pathways seem to be
      conserved in different O-antigen clusters and across a wide range of species. The
      second group, the glycosyl transferases, is involved in sugar transfer. They are
      often dispersed throughout the cluster and have low levels of similarity. The
      third group is the O-antigen processing genes. This review is a summary of the
      current knowledge on these three groups of genes that comprise the O-antigen gene
      clusters, focusing on the most extensively studied E. coli and S. enterica gene
      clusters.

PMID- 14670713
TI  - The biosynthesis and biological role of lipopolysaccharide O-antigens of
      pathogenic Yersiniae.
AB  - Lipopolysaccharide (LPS) is the major component of the outer leaflet of the outer
      membrane of Gram-negative bacteria. The LPS molecule is composed of two
      biosynthetic entities: the lipid A--core and the O-polysaccharide (O-antigen).
      Most biological effects of LPS are due to the lipid A part, however, there is an
      increasing body of evidence indicating that O-antigen (O-ag) plays an important
      role in effective colonization of host tissues, resistance to complement-mediated
      killing and in the resistance to cationic antimicrobial peptides that are key
      elements of the innate immune system. In this review, we will discuss: (i) the
      work done on the genetics and biosynthesis of the O-ags in the genus Yersinia;
      (ii) the role of O-ag in virulence of these bacteria; (iii) the work done on
      regulation of the O-ag gene cluster expression and; (iv) the impact that the O-ag
      expression has on other bacterial surface and membrane components.

PMID- 14670714
TI  - Biological chemistry of immunomodulation by zwitterionic polysaccharides.
AB  - Capsular polysaccharides isolated from pathogenic bacteria are comprised
      typically of many repeating units from one to eight or more monosaccharides in
      length. These polysaccharides stimulate the murine humoral immune system to
      elicit primarily IgM antibody responses. Studies conducted primarily in the mouse
      have characterized these polymers as T cell-independent antigens. These mouse
      studies and the relatively poor immunogenicity of polysaccharides in human hosts
      have led to the design of vaccines by coupling these polysaccharides to protein
      carriers to stimulate a T cell-dependent response. However, a newly described
      class of bacterial polysaccharides has been characterized that have the ability
      to modulate the cellular immune system. They are structurally diverse, but all
      share a zwitterionic charge motif that allows them to directly interact with T
      cells and antigen-presenting cells to initiate an immunomodulatory T cell
      response. These polymers, termed zwitterionic polysaccharides (ZPSs), elicit T
      cell-derived chemokines and cytokines that influence the immune response
      governing at least one classic host response to bacterial infection: abscess
      formation. This review will describe the biological and structural aspects of
      ZPSs that convey these activities.

PMID- 14670715
TI  - Immunology of bacterial polysaccharide antigens.
AB  - Carbohydrates in the form of capsular polysaccharides and/or lipopolysaccharides
      are the major components on the surface of bacteria. These molecules are
      important virulence factors in many bacteria isolated from infected persons.
      Immunity against these components confers protection against the disease.
      However, developing vaccines based on polysaccharides is difficult and several
      problems have to be solved. First of all, most of the bacterial polysaccharides
      are T-lymphocyte independent antigens. Anti-polysaccharide immune response is
      characterised by lack of T-lymphocyte memory, isotype restriction and delayed
      ontogeny. Children below 2 years of age and elderly respond poorly to
      polysaccharide antigens. Secondly, the wide structural heterogeneity among the
      polysaccharides within and between species is also a problem. Thirdly, some
      bacterial polysaccharides are poor immunogens in humans due to their structural
      similarities with glycolipids and glycoproteins present in man. The T-lymphocyte
      independent nature of a polysaccharide may be overcome by conjugating the native
      or depolymerised polysaccharide to a protein carrier. Such neoglycoconjugates
      have been proven to be efficient in inducing T-lymphocyte dependent immunity and
      to protect both infants as well as elderly from disease. Another approach to
      circumvent the T-lymphocyte independent property of polysaccharides is to select
      peptides mimicking the immunodominant structures. Several examples of such
      peptides have been described.

PMID- 14670716
TI  - Promises and pitfalls of Pseudomonas aeruginosa lipopolysaccharide as a vaccine
      antigen.
AB  - Antibodies directed to the Pseudomonas aeruginosa lipopolysaccharide (LPS) O
      antigens have clearly shown to mediate the most effective immunity to infection
      caused by LPS-smooth strains. Such strains are major causes of disease in
      immunocompromised hosts such as burn or cancer patients, individuals in intensive
      care units, and those who utilize extended-wear contact lenses. Yet producing an
      effective vaccine composed of non-toxic, immunogenic polysaccharides has been
      challenging. The chemical diversity among the different O-antigens representative
      of the 20 major serotypes, plus additional diversity among some O-antigens
      representing variant subtype antigens, translates into a large degree of
      serologic variability that increases the complexity of O-antigen specific
      vaccines. Further complications come from the poor immunogenicity of the major
      protective epitope expressed by some O-antigens, and a large degree of diversity
      in animal responses that preclude predicting the optimal vaccine formulation from
      such studies. Nonetheless human trials over the years of vaccines eliciting O
      antigen immunity have been encouraging, though no vaccine has yet been fully
      evaluated and found to be clinically efficacious. Newer vaccine approaches such
      as using polysaccharide-protein conjugates and passive therapy with monoclonal or
      polyclonal immune sera offer some additional means to try and produce an
      effective immunotherapeutic reagent for this problematic pathogen.

PMID- 14670717
TI  - Synthesis of phosphatidylinositol mannosides (PIMs).
AB  - Two strategies towards the synthesis of phosphatidylinositol mannosides (PIMs)
      were elaborated which permit selective access to the O-1-, O-2-, and the O-6
      position of the myo-inositol residue. Starting materials are 1,2:5,6- and 1,2:4,5
      di-O-cyclohexylidene-DL-myo-inositol, respectively. In the latter case, the
      required assignment to the D- or L-series is based on the transformation of one
      enantiomer into known (-)-liriodentritol. The efficiency and potential
      versatility of the two approaches is exemplified in the synthesis of PIMs (D)-1a
      and its pseudoenantiomer (L)-1b, both having myristoyl residues as part of the
      phosphatidyl moiety.

PMID- 14670718
TI  - Efficient chemical synthesis of both anomers of ADP L-glycero- and D-glycero-D
      manno-heptopyranose.
AB  - A series of anomeric phosphates and ADP-activated L-glycero- and D-glycero-D
      manno-heptopyranoses has been prepared in high overall yields, which provided
      model compounds and substrates in the elucidation of biosynthetic pathways and
      glycosyl transfer reactions of nucleotide-activated bacterial heptoses. The alpha
      anomers of the heptosyl phosphates were obtained in high yield and selectivity
      using the phosphoramidite procedure, whereas the beta-phosphates were formed
      preferentially employing acylation of reducing heptoses with diphenyl
      phosphorochloridate. An efficient route to the formation of the nucleotide
      diphosphate sugars was elaborated by coupling of the O-acetylated phosphates with
      AMP-morpholidate followed by alkaline deprotection to furnish ADP-L- and D
      glycero-alpha-D-manno-heptose in 84 and 89% yield, respectively. Deacetylation of
      the O-acetylated beta-configured ADP heptoses was conducted at strictly
      controlled conditions (-28 degrees C at pH 10.5) to suppress formation of cyclic
      heptose-1,2-phosphodiesters with concomitant release of AMP. Isolation of the
      unstable beta-configured ADP-heptoses by anion-exchange chromatography and gel
      filtration afforded ADP L- and D-glycero-beta-D-manno-heptose in high yields.

PMID- 14670720
TI  - Synthesis of tetra- and pentasaccharides corresponding to the capsular
      polysaccharide of Streptococcus pneumoniae type 9A&L, 9N and 9A.
AB  - Two tetrasaccharides, alpha-D-GlcAp-(1-->3)-alpha-D-Galp-(1-->3)-beta-D-ManpNAc
      (1-->4)-beta-D-Glcp and alpha-D-GlcAp-(1-->3)-alpha-D-Glcp-(1-->3)-beta-D-ManpNAc
      (1-->4)-beta-D-Glcp (protected form), and a pentasaccharide, alpha-D-Glcp-(1-->4)
      alpha-D-GlcAp-(1-->3)-alpha-D-Galp-(1-->3)-beta-D-ManpNAc-(1-->4)-beta-D-Glcp
      have been synthesised from 2-aminoethyl glycoside trisaccharide acceptors in a
      linear approach via consecutive alpha-glycosylations. Ethyl thioglycosides were
      used as glycosyl donors and DMTST in Et(2)O or NIS/TfOH in CH(2)Cl(2) were
      employed as promoters.

PMID- 14670719
TI  - One-pot preparation of a series of glycoconjugates with predetermined antigen
      carrier ratio from oligosaccharides that mimic the O-PS of Vibrio cholerae O:1,
      serotype Ogawa.
AB  - Di-through the pentasaccharide that mimic the upstream terminus of the O-specific
      polysaccharide of Vibrio cholerae O:1, serotype Ogawa were synthesized in the
      form of 5-methoxycarbonylpentyl glycosides and linked to BSA using squaric acid
      diester chemistry. The conjugation reactions were monitored by surface-enhanced
      laser-desorption/ionization-time-of-flight mass spectrometry (SELDI-TOF MS),
      which allowed conducting the conjugation of the synthetic oligosaccharides in a
      controlled way and termination of the reaction when the desired molar hapten-BSA
      ratio had been reached. This made it possible to prepare, from one hapten in a
      one-pot reaction, a series of neoglycoconjugates having different, predetermined
      carbohydrate-carrier ratios. The accuracy of molecular mass determination in
      SELDI-TOF MS analysis could be increased by using the carrier protein as the
      internal standard.

PMID- 14670721
TI  - Chemo-enzymatic synthesis of a tetra- and octasaccharide fragment of the capsular
      polysaccharide of Streptococcus pneumoniae type 14.
AB  - The chemo-enzymatic synthesis is described of tetrasaccharide beta-D-Galp-(1-->4)
      beta-D-Glcp-(1-->6)-[beta-D-Galp-(1-->4)]-beta-D-GlcpNAc-(1-->O(CH(2))(6)NH(2)
      (1) and octasaccharide beta-D-Galp-(1-->4)-beta-D-Glcp-(1-->6)-[beta-D-Galp-(1-
      >4)]-beta-D-GlcpNAc-(1-->3)-beta-D-Galp-(1-->4)-beta-D-Glcp-(1-->6)-[beta-D-Galp
      (1-->4)]-beta-D-GlcpNAc-(1-->O(CH(2))(6)NH(2) (2), representing one and two
      tetrasaccharide repeating units of Streptococcus pneumoniae serotype 14 capsular
      polysaccharide. In a chemical approach, the intermediate linear trisaccharide 3
      and hexasaccharide 4 were synthesized. Galactose residues were beta-(1-->4)
      connected to the internal N-acetyl-beta-D-glucosamine residues by using bovine
      milk beta-1,4-galactosyltransferase. Both title oligosaccharides will be
      conjugated to carrier proteins to be tested as potential vaccines in animal
      models.

PMID- 14670722
TI  - Chemo-enzymatic synthesis of tetra-, penta-, and hexasaccharide fragments of the
      capsular polysaccharide of Streptococcus pneumoniae type 14.
AB  - The chemo-enzymatic synthesis is described of beta-D-Glcp-(1-->6)-[beta-D-Galp-(1
      ->4)]-beta-D-GlcpNAc-(1-->3)-beta-D-Galp-(1-->O(CH(2))(6)NH(2) (1), beta-D-Glcp
      (1-->6)-[beta-D-Galp-(1-->4)]-beta-D-GlcpNAc-(1-->3)-beta-D-Galp-(1-->4)-beta-D
      Glcp-(1-->O(CH(2))(6)NH(2) (2), beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->3)-beta-D
      Galp-(1-->4)-beta-D-Glcp-(1-->O(CH(2))(6)NH(2) (3), and beta-D-Galp-(1-->4)-beta
      D-GlcpNAc-(1-->3)-beta-D-Galp-(1-->4)-beta-D-Glcp-(1-->6)-[beta-D-Galp-(1-->4)]
      beta-D-GlcpNAc-(1-->O(CH(2))(6)NH(2) (4), representing fragments of the repeating
      unit of the Streptococcus pneumoniae serotype 14 capsular polysaccharide. Linear
      intermediate oligosaccharides 5-8 were synthesized via chemical synthesis,
      followed by enzymatic galactosylation using bovine milk beta-1,4
      galactosyltransferase as a catalyst. The title oligosaccharides form suitable
      compounds for conjugation with carrier proteins, to be tested as potential
      vaccines in animal models.

PMID- 14670723
TI  - The structure of the glycopeptides from the fish pathogen Flavobacterium
      columnare.
AB  - Proteolytic digestion of the phenol-water extraction product of the fish pathogen
      Flavobacterium columnare afforded a mixture of glycopeptides in which the
      oligosaccharide moiety was an unusual hexasaccharide composed of 4-O-methyl-2
      acetamido-2-deoxy-D-glucuronic acid (GlcNAcA), D-glucuronic acid (D-GlcA), 2,3-di
      O-acetyl-D-xylose (D-Xyl), 2-O-methyl-D-glucuronic acid (D-GlcA), D-mannose (D
      Man), and 2-O-methyl-L-rhamnose (L-Rha). By the application of high-resolution 1D
      and 2D NMR, mass spectrometry, and chemical analysis, the hexasaccharide
      structure was determined to be: [carbohydrate structure--see text] where all
      monosaccharides have the D-configuration except for 2-O-methyl-L-rhamnose; and
      were in the pyranose form. Only one carbohydrate structure was found. The peptide
      part was represented by tri- to hepta-peptides with a minimal common tripeptide
      fragment Asp-Ser-Ala, extended with Ala and Val.

PMID- 14670724
TI  - Structure of the core-oligosaccharide with a characteristic D-glycero-alpha-D
      talo-oct-2-ulosylonate-(2-->4)-3-deoxy-D-manno-oct-2-ulosonate [alpha-Ko-(2-->4)
      Kdo] disaccharide in the lipopolysaccharide from Burkholderia cepacia.
AB  - The core oligosaccharide in the lipopolysaccharide (LPS) of Burkholderia cepacia
      GIFU 645(T) was investigated. After mild acid hydrolysis of the LPS, a
      heptasaccharide was isolated and identified by chemical analyses, GLC-MS, FABMS,
      and NMR spectroscopy as follows: [carbohydrate structure: see text] where L-alpha
      D-Hep stands for L-glycero-alpha-D-manno-heptose, Ko for D-glycero-D-talo-oct-2
      ulosonic acid, and Kdo for 3-deoxy-D-manno-oct-2-ulosonic acid.

PMID- 14670725
TI  - Structure of a highly phosphorylated lipopolysaccharide core in the Delta algC
      mutants derived from Pseudomonas aeruginosa wild-type strains PAO1 (serogroup O5)
      and PAC1R (serogroup O3).
AB  - Lipopolysaccharides (LPS) were isolated from rough-type mutant strains of
      Pseudomonas aeruginosa (Delta algC) derived from wild-type strains PAO1
      (serogroup O5) and PAC1R (serogroup O3). Structural studies of the LPS core
      region with a special focus on the phosphorylation pattern were performed by 2D
      NMR spectroscopy, including a 1H,(31)P HMQC-TOCSY experiment, MALDI-TOF MS, and
      Fourier-transform ion cyclotron resonance ESIMS using the capillary skimmer
      dissociation technique. Both LPS were found to contain two residues each of 3
      deoxy-D-manno-oct-2-ulosonic acid (Kdo) and L-glycero-D-manno-heptose (Hep), one
      residue of N-(L-alanyl)-D-galactosamine and one O-carbamoyl group (Cm) on the
      distal Hep residue. The following structures of a tetrasaccharide trisphosphate
      from strain PAC1R Delta algC and that carrying an additional ethanolamine
      phosphate group (PEtN) from strain PAO1 Delta algC were elucidated: [carbohydrate
      structre: see text] where R=P in PAC1R Delta algC and PPEtN in PAO1 Delta algC.
      To our knowledge, in this work the presence of ethanolamine diphosphate is
      unambiguously confirmed and its position established for the first time in the
      LPS core of a rough-type strain of P. aeruginosa. In addition, the structure of
      the complete LPS core of wild-type strain P. aeruginosa PAO1 was reinvestigated
      and the position of the phosphorylation sites was revised.

PMID- 14670727
TI  - Exopolysaccharides produced by a clinical strain of Burkholderia cepacia isolated
      from a cystic fibrosis patient.
AB  - Burkholderia cepacia is an opportunistic pathogen involved in pulmonary
      infections related to cystic fibrosis. A clinical strain, BTS13, was isolated and
      the production of exopolysaccharides was tested growing the bacteria on two
      different media, one of which was rich in mannitol as carbon source. The primary
      structure of the polysaccharides was determined using mostly mass spectrometry
      and NMR spectroscopy. On both media an exopolysaccharide having the following
      repeating unit was produced: -->5)-beta-Kdop-(2-->3)-beta-D-Galp2Ac-(1-->4)-alpha
      D-Galp-(1-->3)-beta-D-Galp-(1--> This polysaccharide has already been described
      as the biosynthetic product of another Burkholderia species, B. pseudomallei, the
      microbial agent causing melioidosis. In addition to this, when grown on the
      mannitol-rich medium, B. cepacia strain BTS13 produced another polysaccharide
      that was established to be levan: -->6)-beta-D-Fruf-(2-->. The content of levan
      was about 20% (w/w) of the total amount of polymers. The ability of B. cepacia to
      produce these two exopolysaccharides opens new perspectives in the investigation
      of the role of polysaccharides in lung infections.

PMID- 14670726
TI  - Substitution pattern of 3-deoxy-D-manno-oct-2-ulosonic acid in bacterial
      lipopolysaccharides investigated by methylation analysis of whole LPS.
AB  - 3-Deoxy-D-manno-oct-2-ulosonic acid (Kdo) is a constituent of the inner core part
      of bacterial lipopolysaccharides (LPS). This sugar may contribute to biological
      activities of the LPS, the type of substitution of Kdo is thus of importance and
      this work is aimed at the evaluation of a method for monitoring the substitution
      of Kdo in LPS. The procedure consists of three steps, namely permethylation of
      the lipopolysaccharide, with iodomethane and sodium methylsulfinylmethanide or
      NaOH in Me(2)SO, or with methyl triflate, then the product is methanolysed with
      HCl in MeOH and acetylated with acetic anhydride in pyridine. The resulting
      partially methylated acetates of Kdo methyl glycosides were analyzed by gas
      liquid chromatography-electron impact ionization mass spectrometry (GLC-MS). For
      several derivatives of Kdo, specific GLC retention times and MS fragmentation
      patterns were determined. Lipopolysaccharides from several bacterial strains were
      isolated and analyzed with three different methods of methylation. The complete
      solubilization of the LPS in the acid form allows diminishing possible
      undermethylation. Sodium methylsulfinylmethanide is the most efficient agent in
      the permethylation of the whole LPS, of all the tested procedures. Methylation
      with methyl triflate allows the detection of base labile substituents on Kdo
      residues.

PMID- 14670728
TI  - Structural studies on the lipopolysaccharide core of Proteus OX strains used in
      Weil-Felix test: a mass spectrometric approach.
AB  - The core region of the lipopolysaccharides of Proteus group OX bacteria, which
      are used as antigens in Weil-Felix test for serodiagnosis of rickettsiosis, were
      studied by chemical degradations in combination with ESI FTMS, including infrared
      multi-photon dissociation (IRMPD) MS/MS and capillary skimmer dissociation.
      Structural variants of the inner core region were found to be the same as in
      Proteus non-OX strains that have been studied earlier. The outer core region has
      essentially the same structure in Proteus vulgaris OX19 (serogroup O1) and OX2
      (serogroup O2) and a different structure in Proteus mirabilis OXK (serogroup O3).
      A fragmentation due to the rupture of the linkage between GlcN or GalN and GalA
      was observed in IRMPD-MS/MS of core oligosaccharides and found to be useful for
      screening of Proteus strains to assign structures of the relatively conserved
      inner core region and to select for further studies strains with distinct
      structures of a more variable outer core region.

PMID- 14670729
TI  - Structural characterization of the carbohydrate backbone of the
      lipopolysaccharide of Vibrio parahaemolyticus O-untypeable strain KX-V212
      isolated from a patient.
AB  - Vibrio parahaemolyticus strain KX-V212 of a novel serotype, which does not belong
      to any of the known 13 O-serotypes of this vibrio, was isolated from a patient.
      Its O-antigen harbors a unique strain-specific O-antigenic factor(s), in addition
      to that shared by the O-antigen of V. parahaemolyticus serotype O2. A
      carbohydrate backbone nonasaccharide was isolated from the lipopolysaccharide
      (LPS) of strain KX-V212 by dephosphorylation, reduction and deacylation and found
      to consist of one residue each of D-glucose, D-galactose, D-GlcN, 3-deoxy-D-manno
      oct-2-ulosonic acid (Kdo) and 5-acetamido-7-(N-acetyl-D-alanyl)amino-3,5,7,9
      tetradeoxy-D-glycero-D-galacto-non-2-ulosonic acid (Non5Ac7Ala), and two residues
      each of D-GlcA and L-glycero-D-manno-heptose (LD-Hep). Analysis of the isolated
      and deacylated lipid A showed that this oligosaccharide was an artifact resulting
      from a loss of one GlcN residue from the lipid A backbone. Therefore, the
      carbohydrate backbone of the LPS is a decasaccharide having the structure shown
      below. The initial LPS contains also D-GalA and phosphoethanolamine at unknown
      positions. Both similarity and differences are observed between the LPS of V.
      parahaemolyticus serotype O2 and strain KX-V212. [carbohydrate structure: see
      text]

PMID- 14670730
TI  - Structural elucidation of a novel core oligosaccharide backbone of the
      lipopolysaccharide from the new bacterial species Agrobacterium larrymoorei.
AB  - Agrobacterium larrymoorei is a Gram-negative phytopathogenic bacterium, which
      produces tumours on Ficus benjamina plants and differs from other Agrobacteria
      both genetically and biochemically. The lipopolysaccharide (LPS) plays an
      important role in the pathogenesis of Agrobacteria. The present paper is the
      first report on the molecular primary structure of the core region of an
      Agrobacterium LPS. The following structure of the core and lipid A carbohydrate
      backbone of an R-form LPS of A. larrymoorei was determined by chemical
      degradations and 1D and 2D NMR spectroscopy: [carbohydrate structure: see text]
      All sugars are alpha-D-pyranoses if not stated otherwise, Kdo is 3-deoxy-D-manno
      oct-2-ulosonic acid, Qui3NAcyl is 3,6-dideoxy-3-(3-hydroxy-2,3-dimethyl-5
      oxoprolylamino)glucose, GlcAN and GalAN are amides of GlcA and GalA.

PMID- 14670731
TI  - Structural profiling of lipopolysaccharide glycoforms expressed by non-typeable
      Haemophilus influenzae: phenotypic similarities between NTHi strain 162 and the
      genome strain Rd.
AB  - Non-typeable Haemophilus influenzae (NTHi) is a significant cause of otitis media
      in children. We have employed single and multiple step electrospray ionization
      mass spectrometry (ESIMS) and NMR spectroscopy to profile and elucidate
      lipopolysaccharide (LPS) structural types expressed by NTHi strain 162, a strain
      obtained from an epidemiological study in Finland. ESIMS on O-deacylated LPS (LPS
      OH) and core oligosaccharide (OS) samples of LPS provided information on the
      composition and relative abundance of glycoforms differing in the number of
      hexoses linked to the conserved inner-core element, L-alpha-D-Hepp-(1-->2)-[PEtn-
      >6]-L-alpha-D-Hepp-(1-->3)-L-alpha-D-Hepp-(1-->5)-[PPEtn-->4]-alpha-Kdop-(2-->6)
      Lipid A of H. influenzae LPS. The strain examined was found to elaborate Hex2 to
      Hex5 LPS glycoform populations having structures identical to those observed for
      H. influenzae strain Rd [Risberg, A.; Masoud, H.; Martin, A.; Richards, J.C.;
      Moxon, E.R.; Schweda, E.K.H. Eur. J. Biochem. 1999, 261, 171-180], the strain for
      which the complete genome has been sequenced. In addition, sialyllactose
      containing glycoforms previously identified in strain Rd as well as several NTHi
      strains, were identified as minor components. Multiple step tandem ESIMS (MS(n))
      on dephosphorylated and permethylated OS provided information on the arrangement
      of glycoses within the major population of glycoforms and on the existence of
      additional isomeric glycoforms. Minor Hex1 and Hex6 glycoforms were detected and
      characterized where the Hex6 glycoform was comprised of a dihexosamine-containing
      pentasaccharide chain attached at the proximal heptose residue of the inner-core
      unit. LPS structural motifs present in the NTHi strain 162 are expressed by a
      genetically diverse set of disease causing isolates, providing the basis for a
      vaccine strategy against NTHi otitis media.

PMID- 14670732
TI  - A mannitol teichoic acid containing rhamnose and pyruvic acid acetal from the
      cell wall of Brevibacterium permense VKM Ac-2280.
AB  - The cell wall of Brevibacterium permense VKM Ac-2280 contains two teichoic acids.
      The major polymer represents a 1,6-poly(mannitol phosphate) substituted wirh
      either L-rhamnose (approximately 70%, unit A) or (S)-acetal of pyruvic acid
      (approximately 30%, unit B) with the overall chain length approximately 10
      mannitol phosphate units. [carbohydrate structure: see text] The other polymer is
      an unsubstituted 1,3-poly(glycerol phosphate). The structures of the polymers
      were established using chemical degradations and NMR spectroscopy. The data
      obtained may be helpful in determination of the species-specific status of newly
      isolated Brevibacterium strains.

PMID- 14670733
TI  - Structural and serological characterisation of the O-antigenic polysaccharide of
      the lipopolysaccharide from Acinetobacter baumannii strain 24.
AB  - Extraction of dry bacteria of Acinetobacter baumannii strain 24 by phenol-water
      yielded a lipopolysaccharide (LPS) that was studied by serological methods and
      fatty acid analysis. After immunisation of BALB/c mice with this strain,
      monoclonal antibody S48-3-13 (IgG(3) isotype) was obtained, which reacted with
      the LPS in western blot and characterized it as S-form LPS. Degradation of the
      LPS in aqueous 1% acetic acid followed by GPC gave the O-antigenic
      polysaccharide, whose structure was determined by compositional analyses and NMR
      spectroscopy of the polysaccharide and O-deacylated polysaccharide as
      [carbohydrate structure: see text] where QuiN4N is 2,4-diamino-2,4,6
      trideoxyglucose and GalNAcA 2-acetamido-2-deoxygalacturonic acid. The amino group
      at C-4 of the QuipN4N residues is acetylated in about 2/3 of LPS molecules and
      (S)-3-hydroxybutyrylated in the rest.

PMID- 14670734
TI  - The structure of the polysaccharide part of the LPS from Serratia marcescens
      serotype O19, including linkage region to the core and the residue at the non
      reducing end.
AB  - The structure of the LPS from Serratia marcescens serotype O19 was investigated.
      Deamination of the LPS released the O-chain polysaccharide together with a
      fragment of the core oligosaccharide. The following structure of the product was
      determined by NMR spectroscopy, mass spectrometry, and chemical methods:
      [carbohydrate structure: see text] The main polymer consists of a repeating
      disaccharide V-U and is present on average of 18 units per chain as estimated by
      integration of signals in the NMR spectra. The residue O corresponds to the
      primer, which initiates biosynthesis of the O-chain, and an oligomer of a
      disaccharide R-S is an insert between the primer and the main polymer. The
      polysaccharide has a beta-Kdo residue at the non-reducing end, a feature similar
      to that observed previously in the LPS from Klebsiella O12.

PMID- 14670735
TI  - Hydrodynamic properties of oxidized extracellular polysaccharides from Erwinia
      chrysanthemi spp.
AB  - The molecular weights of the native polysaccharides of Erwinia chrysanthemi
      strains range from 1.8 to 7.1 x 10(6) and their hydrodynamic properties are those
      of polydisperse, polyanionic biopolymers with pseudoplastic, non-thixotropic flow
      characteristics in aqueous solutions. The effect on the hydrodynamic properties
      of the polysaccharides by adding carboxyl groups to increase the charge density
      is studied, with particular reference to their molecular weight (MW), viscosity
      and conformation. In general, it is found that periodate oxidation of the
      extracellular polysaccharides of E. chrysanthemi strains, Ech9Sm6 and Ech6S+,
      introduces little change in the hydrodynamic properties of the resulting
      polyaldehydes. However, bromine oxidation at neutral pH of the polyaldehydes
      results in polycarboxylate biopolymers that show significant reduction in MW and
      viscosity, but they are still characteristic polyanions.

PMID- 14670737
TI  - Quantitative liquid chromatographic determination of sanguinarine in cell culture
      medium and in rat urine and plasma.
AB  - Sanguinarine is a quaternary benzo[c]phenanthridine alkaloid, extracted from the
      argemone oil, which produced severe human intoxications. To investigate the
      sanguinarine biotransformation, we develop a simple extraction process and a high
      performance liquid chromatographic separation coupled to a sensitive fluorometric
      detection of sanguinarine in cell culture medium, as well as in rat urine and
      plasma. After extraction with an acidified organic solvent, sanguinarine elution
      is performed within 15 min on a Nucleosil C18 column with a gradient using 0.2%
      formic acid/water/acetonitrile as mobile phase. Extracted and standard
      sanguinarine are characterized by mass spectrometry. The extraction recovery of
      sanguinarine is about 80% in cell culture medium and in rat urine, but lower in
      plasma. This convenient high performance liquid chromatography (HPLC) method
      allows to quantify sanguinarine over concentrations ranged 10-2000 ng ml(-1). The
      limit of fluorometric detection is 0.5 ng. Under these conditions, the lower
      limit of quantification of sanguinarine is 50 ng ml(-1) in cell culture medium
      and in rat urine and 100 ng ml(-1) in rat plasma. This analytical HPLC method is
      specific, linear and reproducible in all media and is suitable for quantitative
      determination of sanguinarine in biological fluids.

PMID- 14670738
TI  - Determination of plasma ziprasidone using liquid chromatography with fluorescence
      detection.
AB  - A liquid chromatographic procedure was developed for the determination of a new
      antipsychotic agent ziprasidone in plasma using fluorescence detection. A one
      step liquid-liquid extraction from 1 ml of alkalinized plasma containing an
      internal standard alpha-ergocryptine using methyl-t-butyl ether afforded a
      greater than 84% recovery of ziprasidone. Chromatography was performed using a
      reversed-phase trimethylsilyl bonded silica column with a mobile phase of 72:28
      phosphate buffer:acetonitrile at a flow rate of 1.5 ml/min. Detection of the
      eluted peaks was observed using excitation and emission wavelengths of 320 and
      410 nm, respectively. Chromatographic run time did not exceed 14 min with no
      interference from endogenous material. The calibration curve was linear over the
      concentration range of 0.5 to 200 ng/ml and the inter- and intra-assay
      imprecision (CV) was less than 10%. The lower limit of quantitation was assessed
      at 0.5 ng/ml. Specificity of the method is demonstrated by the lack of
      interference from a large number of commonly used drugs and their metabolites in
      clinical use. The utility of the method is exemplified with the presentation of
      clinical data from patients receiving ziprasidone.

PMID- 14670739
TI  - Determination of trivalent methylated arsenicals in rat urine by liquid
      chromatography-inductively coupled plasma mass spectrometry after solvent
      extraction.
AB  - A method for the determination of trivalent arsenicals in urine was examined.
      Trivalent arsenicals, extracted as complexes with diethylammonium
      diethyldithiocarbamate (DDDC) into carbon tetrachloride, were determined by
      liquid chromatography-inductively coupled plasma mass spectrometry (LC-ICP-MS).
      The trivalent methylated arsenicals monomethylarsonous acid (MMA(III)),
      dimethylarsinous acid (DMA(III)), and trimethylarsine (TMA) were detected in
      urine of rats that had received dimethylarsinic acid (DMA(V)) or
      monomethylarsonic acid (MMA(V)) at concentration of 200 microg ml(-1) in drinking
      water for 24 weeks. This method is the first to permit quantification of
      trivalent methylated arsenicals in urine without significant changes in
      concentration during storage or pretreatment.

PMID- 14670740
TI  - Determination of new derivatives of genistein in culture media by liquid
      chromatography.
AB  - Methods for determination of genistein and its four new analogues in culture
      media have been developed to support studies on their potential anticancer
      activities. The investigated compounds were extracted from the media using liquid
      liquid extraction with appropriate solvent. After evaporation of organic solvents
      each of the dry extracts was reconstituted in appropriate mobile phase. Reversed
      phase HPLC was applied to quantitative determining of tested compounds. The
      methods are specific, sensitive and technically simple. They were used to
      evaluate concentration level of investigated compounds in experiments with human
      promyelocytic leukemia cells (HL-60 cell line).

PMID- 14670741
TI  - Albendazole sulphoxide concentrations in plasma of endemic normals from a
      lymphatic filariasis endemic region using liquid chromatography.
AB  - A simple and sensitive reversed-phase isocratic HPLC method for the determination
      of albendazole and its metabolites has been developed. The mobile phase
      consisting of acetonitrile-water-perchloric acid (70%) (30:110:0.06 (v/v/v)) was
      pumped at a flow rate of 0.80 ml/min on a 5 microm, reverse phase, Discovery
      RPamide C16 column with UV detection at 290 nm. The calibration graphs were
      linear in the range of 0.05- 1 microg/ml for albendazole, albendazole sulphoxide
      and albendazole sulphone. The limit of quantification was 50 ng/ml for
      albendazole, 25 ng/ml for albendazole sulphoxide and 30 ng/ml for albendazole
      sulphone. The within-day and day-to-day coefficient of variation averaged 4.98
      and 6.95% for albendazole, 3.83 and 6.83% for albendazole sulphoxide and 3.44 and
      5.51% for albendazole sulphone, respectively. The mean extraction recoveries of
      albendazole, albendazole sulphoxide and albendazole sulphone were 79.25, 93.03
      and 88.78%, respectively. The method was applied to determine the plasma levels
      of albendazole sulphoxide in endemic normals administered with albendazole during
      pharmacokinetic studies.

PMID- 14670742
TI  - Purification of alcohol dehydrogenase from bovine liver crude extract by dye
      ligand affinity counter-current chromatography.
AB  - Alcohol dehydrogenase (ADH) was extracted from a crude bovine liver homogenate by
      dye-ligand affinity counter-current chromatography (CCC) using a cross-axis coil
      planet centrifuge (x-axis CPC). The purification was performed using two types of
      polymer phase systems composed of 4.4% polyethylene glycol (PEG) 8000-7.0%
      dextran T500-0.1 M potassium phosphate buffers and 16% PEG 1000-12.5% potassium
      phosphate buffers, both containing a procion red dye as an affinity ligand at
      various pH values. The best purification was achieved using the PEG 1000
      potassium phosphate system at pH 7.3 containing 0.05% procion red as a ligand.
      The upper PEG-rich phase containing procion red was used as the stationary phase
      and a crude bovine liver homogenate was eluted with the potassium phosphate-rich
      lower phase at 0.5 ml/min. After elution of bovine liver proteins in the
      homogenate, ADH still retained in the stationary phase was collected from the
      column by eluting with the PEG 1000-rich upper phase. Collected fractions were
      analyzed by ADH enzymatic activity and by sodium dodecyl sulfate (SDS)
      polyacrylamide gel electrophoresis (PAGE) to detect contaminant proteins in the
      ADH fractions. The ADH was purified directly from crude bovine liver extract
      within 6h with minimum loss of its enzymatic activity.

PMID- 14670743
TI  - Simultaneous determination of tyrosine, phenylalanine and deoxyguanosine
      oxidation products by liquid chromatography-tandem mass spectrometry as non
      invasive biomarkers for oxidative damage.
AB  - We developed an isotope dilution HPLC-atmospheric pressure chemical ionization
      tandem mass spectrometry (HPLC-APCI-MS/MS) method for the simultaneous
      determination of p-tyrosine, phenylalanine, o,o'-dityrosine, m-tyrosine, o
      tyrosine, 3-chlorotyrosine and 3-nitrotyrosine and 8-hydroxy-2'-deoxyguanosine (8
      OHdG) that requires no extensive sample pre-treatment. p-[(2)H(4)]Tyrosine and
      o,o'-[(2)H(6)]dityrosine were used as internal standards. Calibration curves of
      the method were linear (r(2)=0.990-0.999) over a concentration range of 0.03-10
      microM for o-tyrosine; 0.04-10 microM for 3-nitrotyrosine and 3-chlorotyrosine;
      0.05-10 microM for o,o'-dityrosine; and for m-tyrosine; 1.0-100 microM for p
      tyrosine and for phenylalanine; and 0.01-10 microM for 8-OHdG. The detection
      limits were from 0.025 to 0.05 microM for the tyrosine derivatives; 0.01 microM
      for 8-OHdG; and 0.5 microM for p-tyrosine and for phenylalanine, respectively.
      Within-day coefficients of variation (CV) for spiked human urine samples ranged
      from 2.7 to 7.0%, except for 8-OHdG (13.7%). Between-day variations ranged from
      7.9 to 13.0%, except for o-tyrosine (CV = 18.2%), and for 8-OHdG (CV = 24.7%).
      The background levels of p-tyrosine, phenylalanine, o,o'-dityrosine, and o
      tyrosine in morning urine of eight healthy volunteers were 3890+/-590, 3420+/
      730, 5.8+/-0.3, and 9.2+/-1.5 micromol/mol creatinine, respectively. Using the
      present HPLC-APCI-MS/MS method, the urinary background levels of m-tyrosine, 3
      chlorotyrosine, 3-nitrotyrosine and 8-OHdG were below the limit of detection.

PMID- 14670744
TI  - Development and characterization of an open tubular column containing immobilized
      P-glycoprotein for rapid on-line screening for P-glycoprotein substrates.
AB  - Cellular membranes from a cell line expressing P-glycoprotein (Pgp(+)) and from a
      cell line that does not express Pgp (Pgp(-)) were immobilized on the surface of
      glass capillaries (25 cm x 100 microm i.d.) by non-covalent interactions using
      the avidin-biotin coupling system to create two open tubular columns, Pgp(+)-OT
      and Pgp(-)-OT. Frontal displacement chromatography on the Pgp(+)-OT demonstrated
      that the immobilized Pgp retained its ability to specifically bind the known Pgp
      substrates vinblastin and ketoconazole. The calculated affinities, expressed as
      K(d), for vinblastin and ketoconazole were 97 nM and 12.1 microM, which were
      comparable with previously reported K(d) values of 37 nM and 8.6 microM,
      respectively. The results confirm that the Pgp(+)-OT can be used to
      quantitatively estimate binding affinities for the Pgp. Frontal displacement
      chromatography on the Pgp(-)-OT demonstrated that the immobilized membranes
      retained the ability to bind some Pgp substrates, but that the binding was not
      due to specific binding to Pgp. A cohort of compounds containing high affinity
      Pgp substrates (vinblastin, prazosin) and moderate-low affinity Pgp substrates
      (doxorubicin, verapamil, ketoconazole) and a non-substrate (nicotine) were
      chromatographed on the Pgp(+)-OT and Pgp(-)-OT using fast frontal analysis and
      mass spectrometric detection. The results demonstrated that when the retention on
      the Pgp(+)-OT was corrected by subtraction of the retention on the Pgp(-)-OT, the
      test compounds could be accurately sorted into high, moderate-low and non
      substrate categories. The data from the study indicates that a single 30-min
      parallel chromatographic experiment can be used to rank a compound based upon its
      relative affinity for the immobilized Pgp.

PMID- 14670745
TI  - Determination of gabapentin in human plasma by capillary electrophoresis with
      laser-induced fluorescence detection and acetonitrile stacking technique.
AB  - A sensitive analytical method for gabapentin [1-(aminomethyl) cyclohexaneacetic
      acid] (GBP) in human plasma based on capillary electrophoretic separation and
      laser-induced fluorescence (LIF) detection has been developed. 6
      Carboxyfluorescein succinimidyl ester (CFSE) was used for precolumn
      derivatization of the non-fluorescent drug in plasma. Optimal separation and
      detection were obtained with an electrophoretic buffer of 50mM sodium borate (pH
      9.5) and an air-cooled argon-ion laser (excitation at 488 nm, emission at 520
      nm). A calibration curve ranging from 0.3 to 150 microM was shown to be linear.
      The concentration limit of detection (LOD) in plasma was 60 nM. We also
      demonstrate how the detection limit can be enhanced by using acetonitrile
      stacking technique. With stacking, the limit of detection for gabapentin in
      plasma was 4.8 nM. A calibration curve ranging from 0.03 to 15 microM was shown
      to be linear. Both the within-day and day-to-day reproducibility and accuracy
      were </=10.8 and 6.0%, respectively.

PMID- 14670746
TI  - Validation and application of a liquid chromatography-tandem mass spectrometric
      method for the determination of SCH 211803 in rat and monkey plasma using
      automated 96-well protein precipitation.
AB  - A rapid, sensitive, specific, accurate, and reproducible automated liquid
      chromatography-tandem mass spectrometric (LC-MS/MS) method for the quantitative
      determination of 1'-(2-amino-3-methylbenzoyl)-4-[[[(3
      chlorophenyl)sulfonyl]phenyl]methyl]-1,4'-bipiperidine hydrochloride (SCH 211803)
      in plasma has been developed. The method was validated in rat and monkey plasma
      over the concentration range of 0.5-250 ng/ml using 2H(4)-SCH 211803 as the
      internal standard (IS). Automated 96-well plate protein precipitation (PP) with
      acetonitrile (ACN) was used for sample processing. The method employed a Betasil
      C18 column with a fast gradient for the separation of analyte and internal
      standard from the plasma matrix and a triple quadrupole mass spectrometer
      operated in positive ion multiple reaction monitoring (MRM) mode for detection.
      The method was used for the determination of SCH 211803 plasma concentrations to
      support pre-clinical studies.

PMID- 14670747
TI  - Determination of procarbazine in human plasma by liquid chromatography with
      electrospray ionization mass spectrometry.
AB  - Procarbazine is a cytotoxic chemotherapeutic agent used in the treatment of
      lymphomas and brain tumors. Its pharmacokinetic behavior remains poorly
      understood even though more than 30 years have elapsed since the drug was
      approved for clinical use. To characterize the pharmacokinetics of procarbazine
      in brain cancer patients during a phase I trial, a method for determining the
      drug in human plasma by reversed-phase high-performance liquid chromatography
      (HPLC) with electrospray ionization mass spectrometry (ESI-MS) was developed and
      thoroughly validated. Plasma samples were prepared for analysis by precipitating
      proteins with trichloroacetic acid and washing the protein-free supernatant with
      methyl tert-butyl ether to remove excess acid. The solution was separated on a
      Luna C-18 analytical column using methanol-25 mM ammonium acetate buffer, pH 5.1
      (22:78, v/v) as the mobile phase at 1.0 ml/min. A single-quadrupole mass
      spectrometer with an electrospray interface was operated in the selected-ion
      monitoring mode to detect the [M+H](+) ions at m/z 222.2 for procarbazine and at
      m/z 192.1 for the internal standard (3-dimethylamino-2-methylpropiophenone).
      Procarbazine and the internal standard eluted as sharp, symmetrical peaks with
      retention times (mean+/-S.D.) of 6.3+/-0.1 and 9.9+/-0.3 min, respectively.
      Calibration curves of procarbazine hydrochloride in human plasma at
      concentrations ranging from 0.5 to 50 ng/ml exhibited excellent linearity. The
      mean absolute recovery of the drug from plasma was 102.9+/-1.0%. Using a sample
      volume of 150 microl, procarbazine was determined at the 0.5 ng/ml (1.9 nM) lower
      limit of quantitation with a mean accuracy of 105.2% and an interday precision of
      3.60% R.S.D. on 11 different days over 5 weeks. During this same time interval,
      the between-day accuracy for determining quality control solutions of the drug in
      plasma at concentrations of 2.0, 15 and 40 ng/ml ranged from 97.5 to 98.2%
      (mean+/-S.D., 97.9+/-0.4%) and the precision was 3.8-6.2% (mean+/-S.D., 5.1+/
      1.2%). Stability characteristics of the drug were thoroughly evaluated to
      establish appropriate conditions to process, store and prepare clinical specimens
      for chromatographic analysis without inducing significant chemical degradation.
      The sensitivity achieved with this assay permitted the plasma concentration-time
      profile of the parent drug to be accurately defined following oral administration
      of standard doses to brain cancer patients.

PMID- 14670748
TI  - Relationship between the protein surface hydrophobicity and its partitioning
      behaviour in aqueous two-phase systems of polyethyleneglycol-dextran.
AB  - In order to develop possible correlations to predict partioning behaviour of
      proteins, five mammalian albumins (goat, bovine, equine, human and pig ones) with
      similar physico-chemical properties (molecular mass and isoelectrical point) were
      chosen. Evaluation of the relationship between hydrophobicity and partitioning
      coefficient (Kr) in polyethylenglycol-dextran (PEG-DxT500) systems formed by
      polyethyleneglycols of different molecular mass (3350, 6000 and 10,000) was
      investigated by estimating relative surface hydrophobicity (So) with a
      fluorescent probe, 1 anilino-8-naphthalene sulfonate. No relationship between Kr
      and So was found for systems formed by PEG3350, while aqueous two-phase systems
      with PEG6000 and PEG10,000 gave better correlations. The results obtained may be
      explained on the basis of an increase in the interaction between the latter PEGs
      and the protein due to their higher hydrophobic character which increases as the
      PEG molecular mass does so. In this way, systems with PEGs of higher molecular
      mass give the highest resolution to exploit hydrophobicity in partitioning.

PMID- 14670749
TI  - Analytical derivatization-a tool for determination of orotic acid.
AB  - Derivatization of orotic acid (OA) into various forms (trimethylsilylderivate,
      alkyl ester and per-methylated derivate) and their evaluation by GC/MS is
      described. The tested approach includes ion-exchange SPE clean-up, evaporation
      and chemical reaction with different types of derivatization agents (N,O-bis
      (trimethylsilyl)trifluoroacetamide with trimethylchlorosilane, butanol with
      acetylchloride and ethereal solution of diazomethane). Derivate originated in the
      reaction with diazomethane was used for determination of urinary orotic acid by
      GC/MS. Detection limit of 0.28 micromol l(-1) was reached using the ion 82 m/z in
      single ion monitoring (SIM) mode. Linearity of the method was tested within the
      range of 3.4-2503.4 micromol l(-1) covering physiological and pathological levels
      of orotic acid in urine sample. Recoveries were within the range 93.7-110.6%.
      Application of the method on the patient with defect of ornithine
      transcarbamylase (OTC) was demonstrated as well.

PMID- 14670750
TI  - Reversed-phase liquid chromatography method to determine COL-3, a matrix
      metalloproteinase inhibitor, in biological samples.
AB  - A reversed-phase high-performance liquid chromatographic (HPLC) method with
      ultraviolet (UV) detection was developed and validated for the quantification of
      6-deoxy-6-demethyl-4-dedimethylamino-tetracycline (COL-3), a matrix
      metalloproteinase (MMPs) inhibitor, in rat serum. This simple, sensitive, rapid
      and reproducible assay involved a preliminary serum deproteinization by adding a
      mixture of acetonitrile-methanol-0.5 M oxalic acid (70:20:10 (v/v)), as the
      combined precipitant and metal blocking agent, into serum samples (2:1 (v/v)). An
      aliquot (20 microl) of the supernatant was injected into the HPLC system linked
      to a Waters XTerra RP(18) column (150 mm x 4.6 mm i.d., particle size 5 microm).
      The compound was eluted by a mixture of acetonitrile-methanol-0.01 M oxalic acid
      (40:10:50 (v/v), pH 2.00), as the mobile phase, and detected at the wavelength of
      350 nm. The total running time was 10 min. The low and high concentration
      calibration curves were linear in the range of 50-1200 ng/ml and 1200-12,000
      ng/ml, respectively. The intra- and inter-day coefficients of variation at three
      quality control concentrations of 100, 1200, and 12,000 ng/ml were all less than
      6%, while the percent error ranged from -2.5 to 6.6%. The limit of quantitation
      (LOQ) for COL-3 in serum was 50 ng/ml. This assay was successfully employed to
      study the serum concentration-time profiles of COL-3 after its intravenous and
      oral administration in rats. The method with some minor modifications in sample
      pretreatment was also applicable to the determination of the concentrations of
      COL-3 in rat bile, urine and feces.

PMID- 14670751
TI  - Dynamic coating for fast and reproducible determination of basic drugs by
      capillary electrophoresis with diode-array detection and mass spectrometry.
AB  - The double coating principle of CEofix buffers was evaluated for the analysis of
      some basic drugs by capillary electrophoresis-diode-array detection (CE-DAD) and
      capillary electrophoresis-mass spectrometry (CE-MS). The involatile phosphate
      present in original low pH CEofix, was replaced with formic acid for hyphenation
      of CE with MS. The double coating produces a substantial and highly reproducible
      electroosmotic flow (EOF), even at low pH. The rinsing procedure and electrolyte
      composition were optimized for both CE-DAD and CE-MS. The system was evaluated
      with the analysis of a mixture of basic drugs and a spiked urine sample enriched
      by solid-phase extraction (SPE). The R.S.D. values on the migration time and peak
      area measured for 28 analyses with CE-DAD were below 0.25 and 2.40%,
      respectively. For CE-MS, the R.S.D. on the migration time was 0.85% or less and
      the area precision ranged from 5.65 to 14.33% (for seven injections). The LOD
      with the developed CE-MS method was below 50 ppb for all five drug standards
      tested.

PMID- 14670752
TI  - Rapid and sensitive static headspace gas chromatography-mass spectrometry method
      for the analysis of ethanol and abused inhalants in blood.
AB  - A sensitive and specific method using static headspace gas chromatography coupled
      with mass spectrometry (GC/MS) has been developed for the quantitative
      determination of ethanol in biological fluids using n-propanol as internal
      standard. Gas chromatography was performed in isothermal mode with a GC run time
      of 2.6 min. The quantification was performed using scan mode abstracting a
      quantitative ion and a qualifier ion for ethanol and for the internal standard.
      The method was linear (r(2), 0.999, in the concentration range of 5-200 mg/dl),
      specific (no interference from methanol acetaldehyde, acetone or from endogenous
      materials), sensitive (limit of quantification and limit of detection of 0.2 and
      0.02 mg/dl, respectively) and robust (less than 5% inter- and intra-assay
      coefficient of variation). A slightly modified method was also developed for the
      quantification of five commonly abused inhalants (dichloromethane, ethyl acetate,
      benzene, toluene and xylene) in blood. The method used a gradient GC program with
      a run time of 8 min. The quantification was performed using scan mode and
      integrating the area under the peak using trichloroethane as an internal
      standard. Without optimization, the method was linear (from 5 to 100 mg/l) and
      sensitive.

PMID- 14670753
TI  - Validation of a simplified method for determination of cimetidine in human plasma
      and urine by liquid chromatography with ultraviolet detection.
AB  - A HPLC method was developed for determination of cimetidine in human plasma and
      urine. Plasma samples were alkalinized followed by liquid extraction with water
      saturated ethyl acetate then evaporated under nitrogen. The extracts were
      reconstituted in mobile phase and injected onto a C(18) reversed-phase column; UV
      detection was set at 228 nm. Urine samples were diluted with an internal
      standard/mobile phase mixture (1:9) prior to injection. The lower limit of
      quantification in plasma and urine were 100 ng/ml and 10 microg/ml, respectively;
      intra- and inter-day coefficients of variation were </=4.2%. Advantages of this
      validated assay include a readily available internal standard, simplified plasma
      extraction and urine dilution methods, and applicability to clinical studies
      investigating the renal handling of cimetidine.

PMID- 14670754
TI  - Separation of manganese peroxidase isoenzymes on strong anion-exchange monolithic
      column using pH-salt gradient.
AB  - Different chromatographic methods including chromatofocusing are used for
      separation of manganese peroxidase (MnP) isoforms and their isolation from the
      fungal growth medium. We tested strong anion exchange methacrylate based
      monolithic columns as a stationary phase for fast separation of MnP's. Sodium
      acetate buffers of two different pH values (6 and 4) were used for formation of
      reproducible pH gradient. The entire cycle, involving analysis and column
      regeneration, was completed in 3 min. Use of pH gradient showed better MnP
      isoform separation comparing to the salt gradient, while application of combined
      pH-salt gradient, resulted in further improvement.

PMID- 14670755
TI  - Liquid chromatographic determination of 1-adamantanamine and 2-adamantanamine in
      human plasma after pre-column derivatization with o-phthalaldehyde and 1-thio
      beta-D-glucose.
AB  - We investigated high-performance liquid chromatographic (HPLC) determination of 1
      adamantanamine hydrochloride (1-ADA) and 2-adamantanamine hydrochloride (2-ADA)
      in human plasma after the derivatization with o-phthalaldehyde (OPA) and 1-thio
      beta-D-glucose (TG). Extracted human plasma samples were mixed with OPA and TG at
      room temperature for 6 min and injected onto HPLC. Retention times of 1-ADA and 2
      ADA derivatives were 12.6 and 14.1 min, respectively. The lower limits of
      detection of 1-ADA and 2-ADA were 0.02 and 0.008 microg/ml, and the lower limits
      of quantitation of 1-ADA and 2-ADA were 0.025 and 0.01 microg/ml, respectively.
      The coefficients of variation for intra-day and inter-day assay of 1-ADA and 2
      ADA were less than 4.4 and 6.0%, respectively. L-Dopa and dopamine were not found
      to interfere with the peaks of 1-ADA and 2-ADA derivatives. Human plasma unbound
      fraction (f(p)) values of 1-ADA varied between 0.32 and 0.48, while those of 2
      ADA varied between 0.38 and 0.68. These results indicate that HPLC assay of 1-ADA
      and 2-ADA by derivatization with OPA and TG is simple, rapid, sensitive and
      reproducible for determining 1-ADA and 2-ADA in human plasma.

PMID- 14670756
TI  - Liquid chromatographic method for simultaneous determination of mycophenolic acid
      and its phenol- and acylglucuronide metabolites in plasma.
AB  - A simple, sensitive and reproducible HPLC method is presented for the
      simultaneous determination of mycophenolic acid (MPA) and its metabolites
      phenolic MPA-glucuronide (MPAG) and acyl glucuronide (AcMPAG) in human plasma.
      Sample purification requires protein precipitation with 0.1 M phosphoric
      acid/acetonitrile in the presence of Epilan D as an internal standard (IS).
      Separation was performed by reversed-phase HPLC, using a Zorbax SB-C18 column,
      32% acetonitrile and a 40 mM phosphoric acid buffer at pH 3.0 as mobile phase;
      column temperature was 50 degrees C, flow rate 1.4 ml/min, and measurement by UV
      detection was at 215 nm (run time 12 min). The method requires only 50 microl
      plasma. Detection limits were 0.1 microg/ml for MPA and AcMPAG, and 2.0 microg/ml
      for MPAG, respectively. Mean absolute recovery of all three analytes was >95%.
      This analytical method for the determination of MPA and its metabolites is a
      reliable and convenient procedure that meets the criteria for application in
      routine clinical drug monitoring and pharmacokinetic studies.

PMID- 14670757
TI  - Sudden infant death syndrome.

PMID- 14670758
TI  - Safety of herbal medicines in children.

PMID- 14670759
TI  - Detection of leptospirosis in India.

PMID- 14670760
TI  - The confidential enquiry into maternal and child health (CEMACH).

PMID- 14670762
TI  - Containing anxiety in the management of constipation.

PMID- 14670763
TI  - Intussusception and the great smog of London, December 1952.
AB  - AIM: To discuss the possible significance of the increased incidence of
      intussusception in children in relation to the "Great Smog" of London in December
      1952. METHODS: Cases of intussusception were recorded in two hospitals in East
      London for the years 1951, 1952, 1953, and 1954. For 1952 the actual dates of
      admission were recorded. RESULTS: During the year 1952 the total number of cases
      of intussusception greatly exceeded that in the previous and succeeding years.
      Immediately during and after the fog there was a clustering of cases, which only
      occurred during this period. CONCLUSIONS: The increased incidence of cases during
      1952 is thought to reflect the annual variation in incidence resulting from
      changes in the prevalence of viruses capable of causing intussusception. The
      clustering of cases in relation to the fog may reflect a facilitated entry of
      virus through the wall of the terminal ileum due to the effect of swallowed
      irritants such as sulphurous acid and smoke particles.

PMID- 14670764
TI  - A controlled study of sleep related disordered breathing in obese children.
AB  - BACKGROUND: Unlike the adult sleep related disordered breathing (SDB) patients
      who are typically obese, the relation between obesity and childhood SDB is not
      clear. AIMS: To investigate whether obese children are more at risk of
      obstructive SDB when compared to normal population, and whether this risk is
      potentiated by the presence of pharyngeal lymphoid tissue. METHODS: Forty six
      obese children (age 10.8 (SD 2.3) years; BMI 27.4 (SD 5.1)), and 44 sex and age
      matched normal weight children (age 11.7 (SD 2.1) years; BMI 18 (SD 1.8)) were
      studied. All children underwent a set of physical examinations (including the
      upper airways) and sleep studies. RESULTS: The obese children were different from
      the normal weight children in terms of type (predominantly obstructive),
      frequency, and severity of respiratory disturbances. Depending on the criteria
      used, 26% or 32.6% of obese children had SDB; 2.3% of normal controls had OAI >
      or =1 and 4.5% had RDI > or =5. Presence of SDB was related to presence of
      tonsils (size >2; range 0-4) (OR 12.67, 95% CI 2.14 to 75.17) and BMI (OR 1.20,
      95% CI 1.08 to 1.33). CONCLUSIONS: Results suggest that obese children are at
      increased risk of obstructive SDB; the presence of any pharyngeal lymphoid tissue
      enlargement in obese children should therefore be aggressively managed.

PMID- 14670766
TI  - Nocturnal enuresis is a common complication following cardiac transplantation.
AB  - AIMS: To investigate the incidence of nocturnal enuresis post-cardiac
      transplantation. METHODS: Seventy two cardiac transplantations have been
      performed in children under 16 years of age. All recipients who were alive and
      over 4 years of age at the time of the study received a questionnaire about
      urinary symptoms; 54 of the 57 eligible children participated. RESULTS: Twenty
      five children had persistent nocturnal enuresis post-transplantation. Thirteen of
      them had previously attained reliable night-time dryness but developed secondary
      nocturnal enuresis following transplantation, with three subsequently regaining
      dryness at ages 8, 12, and 17 years; 10 were still wetting mean age 12.3. Twelve
      children had not achieved night-time dryness when transplanted (all were under 4
      years of age at the time) and continued to wet. Only one of these children
      achieved dryness (at age 12 using oxybutynin); the other 11 remained wet at night
      at a mean age of 9.3 years. Twenty nine children were dry at night post
      transplantation, but 21 of them had nocturia at least three times a week. There
      is a significant difference in age at transplantation between the primary
      nocturnal enuretic children (mean age 2.0) and the secondary nocturnal enuretic
      children (mean age 7.4) as well as between the primary nocturnal enuretic
      children and the non-enuretic children (mean age 9.0). CONCLUSIONS: Transplanting
      young children frequently delays the normal attainment of night-time continence
      or causes them to start wetting again. It should not be dismissed as a minor
      problem as it causes low self-esteem and is socially limiting. It is important
      families are aware it is a direct result of the transplantation process.

PMID- 14670767
TI  - Central core disease: clinical, pathological, and genetic features.
AB  - Central core disease (CCD) is a dominantly inherited congenital myopathy allelic
      to malignant hyperthermia (MH) caused by mutations in the RYR1 gene on chromosome
      19q13.1. Eleven individuals with RYR1 mutations are described. Four index cases
      showed features consistent with a congenital myopathy (hypotonia, delayed motor
      milestones, and skeletal abnormalities including congenital hip dislocation and
      scoliosis). All four cases and subsequently seven other family members were found
      to possess novel mutations in the RYR1 gene. The degree of disability varied from
      one clinically normal individual, to another who had never achieved independent
      ambulation (the only patient with a de novo mutation). Four cases showed a mild
      reduction in vital capacity, repeated nocturnal polysomnography showed hypoxaemia
      in one case. A variety of muscle biopsy features were found; central cores were
      absent in the youngest case, and the biopsy specimens from two others were more
      suggestive of mini-core myopathy. In all cases missense mutations in exons 101,
      102, and 103 of the RYR1 gene on were found. Future laboratory diagnosis of
      suspected cases and family members will be less invasive and more accurate with
      DNA analysis. Clinicians, especially paediatricians and orthopaedic surgeons,
      should be aware of this disorder because of the potential risk of MH.

PMID- 14670768
TI  - Herbal creams used for atopic eczema in Birmingham, UK illegally contain potent
      corticosteroids.
AB  - AIMS: To determine whether "herbal creams" reported as being effective for the
      treatment of childhood atopic eczema contained corticosteroids. METHODS: Patients
      attending the paediatric dermatology clinic at Birmingham Children's Hospital,
      April 2001 to March 2002, and who reported using "herbal creams" with good effect
      for atopic eczema were asked to submit the cream for analysis. Hydrocortisone,
      clobetasone butyrate, betamethasone valerate, and clobetasol propionate were
      analysed by HPLC. RESULTS: Twenty four creams from 19 patients, median
      (interquartile range) age 3.82 (0.69-7.98) years were analysed. All five creams
      labelled Wau Wa and the two labelled Muijiza cream contained clobetasol
      propionate. Thirteen of 17 unnamed creams contained corticosteroids: clobetasol
      proprionate (n = 4), clobetasol proprionate + hydrocortisone (n = 1),
      betamethasone valerate (n = 2), clobetasone butyrate (n = 3), and hydrocortisone
      (n = 2); there was an unidentified peak in one. Further analysis suggested Wau Wa
      cream contained approximately 20% proprietary Dermovate Cream in a paraffin base.
      No parents were aware that the creams contained steroid. CONCLUSIONS: The
      majority of herbal creams analysed illegally contained potent or very potent
      topical steroids. There is an urgent need for tighter regulation of herbal creams
      and for increased public education about the potential dangers of alternative
      therapies.

PMID- 14670769
TI  - Factors relating to the infant's last sleep environment in sudden infant death
      syndrome in the Republic of Ireland.
AB  - AIM: To identify risk factors for sudden infant death syndrome (SIDS) in the
      sleeping environment of Irish infants. METHODS: A five year population based case
      control study with parental interviews conducted for each case and three controls
      matched for age, place of birth, and last sleep period. A total of 203 SIDS cases
      and 622 control infants born 1994-98 were studied. RESULTS: In a multivariate
      analysis, co-sleeping significantly increased the risk of SIDS both as a usual
      practice (adjusted OR 4.31; 95% CI 1.07 to 17.37) and during the last sleep
      period (adjusted OR 16.47; 95% CI 3.73 to 72.75). The associated risk was
      dependent on maternal smoking (OR 21.84; 95% CI 2.27 to 209.89), and was not
      significant for infants who were > or =20 weeks of age (OR 2.63; 95% CI 0.49 to
      70.10) or placed back in their own cot/bed to sleep (OR 1.07; 95% CI 0.21 to
      5.41). The use of pillows, duvets, and bedding with tog value > or =10 were not
      significant risk factors when adjusted for the effects of confounding variables,
      including maternal smoking and social disadvantage. However, the prone sleeping
      position remains a significant SIDS risk factor, and among infants using
      soothers, the absence of soother use during the last sleep period also
      significantly increased the SIDS risk (OR 5.83; CI 2.37 to 14.36). CONCLUSION: Co
      sleeping should be avoided in infants who are <20 weeks of age, or whose mothers
      smoked during pregnancy. The prone position remains a factor in some SIDS deaths,
      and the relation between soother use and SIDS is a complex variable requiring
      further study.

PMID- 14670770
TI  - The clinical and health economic burden of respiratory syncytial virus disease
      among children under 2 years of age in a defined geographical area.
AB  - AIMS: To describe the clinical and health economic impact of respiratory
      syncytial virus (RSV) disease in children under 2 years of age. METHODS:
      Hospitalised children less than 2 years of age with a respiratory illness were
      studied over three consecutive RSV seasons (1996-99). RESULTS: The rates (per
      1000 infants under 1 year of age) of hospitalisations from bronchiolitis and RSV
      illness were 30.8 and 24.4 respectively. The rates of death, intensive care
      admission, and need for ventilatory assistance during RSV related hospitalisation
      were 0.2%, 2.7%, and 1.5% respectively. From a cohort of 841 preterm infants,
      6.3% had an RSV related hospitalisation during the study period, with the rate
      rising to 9.2% among those who were either born before 36 weeks gestation and
      were under 6 months of age at the onset of the RSV seasons, or were less than 2
      years of age with chronic lung disease needing home oxygen therapy. Eight of 25
      children on home oxygen therapy had RSV related rehospitalisation. Need for
      assisted ventilation during the neonatal period and discharge home on oxygen
      therapy were significantly associated with the risk of subsequent RSV related
      hospitalisation in preterm infants less than 6 months of age. The direct health
      authority cost of all RSV hospitalisations was pound 542 203, while the currently
      recommended immunoprophylaxis for the high risk infants would have cost pound 652
      960. CONCLUSIONS: Preterm infants receiving assisted ventilation and those on
      home oxygen therapy are particularly at risk of RSV related hospitalisation.
      Serious adverse outcomes are however uncommon even among these high risk infants.

PMID- 14670771
TI  - An observational study to detect leptospirosis in Mumbai, India, 2000.
AB  - BACKGROUND: Leptospirosis is relatively uncommon in children. Following
      torrential rains and flooding an outbreak of leptospirosis was suspected in
      Mumbai. AIMS: To investigate the possibility of an outbreak of leptospirosis and
      describe the clinical illness. METHODS: From 24 July to 14 September 2000,
      children with a history of abrupt onset of high fever (>39 degrees C), who
      presented to our hospital, were admitted and tested serologically for anti
      Leptospira antibodies by a quantitative enzyme linked immunosorbent assay (ELISA)
      test. An IgM titre of more than 20U/ml confirmed the diagnosis of leptospirosis.
      Clinical features in the confirmed leptospirosis and leptospirosis negative
      groups were analysed. RESULTS: Of 53 children screened, 18 (34%) had
      leptospirosis. In all 18, the disease was anicteric and responded well to
      intravenous penicillin. Four clinical features present at the time of admission
      were significantly associated with leptospirosis: a history of contact with flood
      water (18/18 v 16/35), conjunctival suffusion (5/18 v 1/35), abdominal pain (9/18
      v 5/35), and skin rash (5/18 v 1/35). As the number of these four features
      concomitantly present increased, the chances of the child having leptospirosis
      also increased significantly. A history of contact with flood water had a
      sensitivity of 100%, and the presence of conjunctival suffusion, abdominal pain,
      and skin rash had a specificity of 97%, 86%, and 97%, respectively, for
      identifying children with leptospirosis. CONCLUSION: Leptospirosis should be
      suspected in febrile children with contact with flood water.

PMID- 14670772
TI  - Childhood constipation is not associated with characteristic fingerprint
      patterns.
AB  - BACKGROUND: It has been suggested that there is an association between simple
      arch fingerprint patterns and severe childhood constipation. If real, this
      association might be useful to predict which children have a poor prognosis. AIM:
      To see how many severely constipated children have simple arches, compared to non
      constipated controls and their first degree relatives. METHODS: Fingerprints were
      classified by two blinded assessors in 30 children requiring surgery for
      refractory constipation, and 30 children with appendicitis, and the first degree
      relatives of both groups. Colonic transit times and clinical outcomes were also
      evaluated among constipated children. RESULTS: At least one simple arch was found
      in similar numbers of constipated children (13%) and their families (16%), and
      control children (7%) and their families (13%). Arch positivity was commoner
      among relatives of arch positive (6/6) than arch negative children (14/54),
      regardless of bowel history. Arch positivity did not identify children with
      prolonged transit times, nor those who required colectomy. CONCLUSIONS:
      Fingerprint patterns are not associated with severe childhood constipation, do
      not aid their management, and do not support a genetic aetiology for this
      problem.

PMID- 14670774
TI  - Hepatitis B incidence among South Asian children in England and Wales:
      implications for immunisation policy.
AB  - The incidence of acute hepatitis B virus (HBV) infection is higher among South
      Asian than among non-South Asian UK residents, and infections in South Asians
      occur more often during childhood. The UK's immunisation policy should be changed
      to protect ethnic minority children against HBV infection.

PMID- 14670773
TI  - Prospective randomised treatment with recombinant human growth hormone in cystic
      fibrosis.
AB  - AIM: To evaluate the efficacy and safety of treatment with recombinant growth
      hormone (rGH) in patients with cystic fibrosis (CF). METHODS: Twenty patients
      with CF (aged 10-23 years) were randomised to age and sex matched treatment and
      control groups. The treatment group received daily subcutaneous injections of 1
      IU/kg/wk rGH for 12 months. Pulmonary function (forced expiratory volume in one
      second (FEV1) and airway resistance), exercise capacity measured with a bicycle
      ergometer, body composition (dual energy x ray absorptiometry), and weight were
      assessed at the beginning of the study and after 6 and 12 months. RESULTS: rGH
      treatment did not improve weight and pulmonary function, but lean body mass
      increased significantly in the treatment group. Exercise capacity increased in
      the treatment group from 143 (16) W (mean (SD)) to 164 (19) W after 12 months of
      rGH treatment. CONCLUSION: Treatment of CF patients with rGH for one year
      improved the exercise capacity significantly but not pulmonary function. The
      improved exercise capacity needs confirmation in a larger population before such
      an expensive treatment is justified.

PMID- 14670775
TI  - Baby walkers: paediatricians' knowledge, attitudes, and health promotion.
AB  - Paediatricians were surveyed about baby walker knowledge, attitudes, and
      practice. Advising about walkers was associated with working in community
      paediatrics, treating walker related injuries, knowledge about walkers, and
      positive attitudes towards walker health promotion. Greater knowledge about
      walkers was associated with more negative attitudes to walkers. Educating
      paediatricians and parents about the risks of, and alternatives to using walkers
      is important.

PMID- 14670776
TI  - Adverse health effects of prenatal and postnatal tobacco smoke exposure on
      children.
AB  - Parents who choose to smoke are possibly not aware of, or deny, the negative
      effects of passive smoking on their offspring. This review summarises a wide
      range of effects of passive smoking on mortality and morbidity in children. It
      offers paediatricians, obstetricians, specialists in preventive child health
      care, general practitioners, and midwives an approach to promote smoking
      cessation in smoking parents before, during, and after pregnancy.

PMID- 14670777
TI  - Mortality in paediatric epilepsy.
AB  - The reasons for premature death in paediatric epilepsy are reviewed with
      reference to recent studies reported in the literature. Ways of informing
      families of children with epilepsy about the risk of death are discussed, and
      recommendations for personal practice given.

PMID- 14670779
TI  - Sudden infant death syndrome: a critical review of approaches to research.
AB  - This review explores the various research approaches taken attempting to solve
      the problem of SIDS. It would appear that major clues provided by pathological
      findings have been largely overlooked and as a consequence much effort, time, and
      money has been wasted on projects that satisfy only sub-specialty and political
      needs. Close examination of the pathological clues would provide better insights
      into the mechanisms underlying this enigmatic and heartbreaking problem.

PMID- 14670781
TI  - Culture confirmed multidrug resistant tuberculosis: diagnostic delay, clinical
      features, and outcome.
AB  - AIMS: To determine the delay in diagnosis of multidrug resistant (MDR)
      tuberculosis (TB), the correlation between drug susceptibility patterns of adult
      child contact pairs, the effectiveness of treatment, and the outcome in these
      children. METHODS: MDR M tuberculosis culture results of children were
      prospectively collected during a four year period in the Western Cape Province of
      South Africa, an area with a TB incidence of 589/100 000 population, and a new
      MDR TB rate of 0.94%. Folder reviews were done to retrieve clinical information.
      Children not already on treatment at our MDR TB clinic or TB hospital were
      recalled and appropriate treatment was started. Follow up was done for as long as
      possible. RESULTS: Thirty nine children, median age 4.5 years at first TB
      diagnosis and 6.2 years on MDR culture confirmation, were seen. Delay in starting
      appropriate MDR treatment after TB diagnosis was a median of 2 days if MDR TB
      source cases were taken into account, but 246 days if the drug susceptibility
      pattern of the source case was not considered, and 283 days if there was no known
      tuberculosis source case. Correlation between the drug susceptibility results of
      the child's and adult source case's isolates was 68%. Seventeen children had
      smear positive tuberculosis, of whom 13 had cavitatory pulmonary disease. Eight
      children had central nervous system TB. Thirty six children were treated for MDR
      tuberculosis, of whom four died. CONCLUSIONS: Obtaining a detailed contact
      history is essential as a delay in starting appropriate MDR antituberculosis
      treatment has potentially serious consequences.

PMID- 14670780
TI  - Pulmonary and sinus diseases in primary humoral immunodeficiencies with chronic
      productive cough.
AB  - AIMS: To prospectively evaluate sinopulmonary disease in 24 patients with primary
      humoral immunodeficiency (11 with agammaglobulinaemia, nine with isolated IgA
      deficiency, and two with common variable immunodeficiency) and chronic productive
      cough, ascertain the usefulness of chest high resolution computed tomography
      (HRCT) in evaluating the progression of lung disease, and test a therapeutic
      approach to chronic sinusitis. METHODS: Pulmonary abnormalities were evaluated
      using lung function tests and HRCT (Bhalla score); chronic sinusitis was
      diagnosed clinically and confirmed by flexible fibreoptic endoscopy. Sixteen
      patients entered the three year follow up. RESULTS: Lung function testing
      revealed an obstruction in four patients; chest HRCT was abnormal in 16. There
      was a linear relation between the Bhalla score > or =4 and the number of months
      with cough/year over the previous two years (clinical score), and between the
      difference in clinical scores during follow up and in the previous two years and
      the difference in Bhalla score. The pulmonary lesions did not significantly
      progress over a three year period. Thirteen patients had chronic sinusitis; 6/10
      patients followed up were successfully treated with antibiotics plus topical
      therapy and two with nasal polypoid disease with endoscopic sinus surgery.
      CONCLUSIONS: In patients with primary humoral immunodeficiency and chronic
      productive cough, HRCT is very useful in delineating the extent of lung damage.
      The correlation between Bhalla score and clinical findings and the favourable
      outcome of the disease suggests that in most patients chest HRCT should not be
      repeated annually as previously suggested. Medical therapy seems to be effective
      in many cases of chronic sinusitis.

PMID- 14670783
TI  - Brain haemorrhage in five infants with coagulopathy.
AB  - Most intracranial haemorrhages in infants after the neonatal period are secondary
      to non-accidental injury. Occasionally brain haemorrhages in non-mobile infants
      are due to an inherited coagulopathy. This may often be diagnosed with a
      coagulation screen on admission. Little is known about the neurological outcome
      of infants in the latter group. Five infants are described who presented with
      acute spontaneous brain haemorrhage secondary to an inherited coagulopathy (n =
      3) and vitamin K deficiency in alpha(1) antitrypsin deficiency (n = 1) and
      Alagille's syndrome (n = 1). Despite the critical clinical presentation and the
      severe imaging findings, these five infants made a good neurological recovery.
      Infants presenting with spontaneous ICH due to a significant (inherited)
      coagulopathy are usually easy to differentiate from non-accidental shaking
      injury; their bleeding pattern within the brain seems different from non
      accidental shaking injury and neurodevelopment outcome appears better.

PMID- 14670782
TI  - The effect of HIV infection on paediatric bacterial meningitis in Blantyre,
      Malawi.
AB  - AIM: To compare presentation, progress, and outcome of acute bacterial meningitis
      in HIV seropositive and seronegative children. METHODS: A double blind randomised
      placebo controlled study of the use of dexamethasone as adjuvant therapy in acute
      bacterial meningitis, in children aged 2 months to 13 years, was carried out from
      July 1997 to March 2001. A total of 598 children were enrolled, of whom 459 were
      tested for HIV serostatus. RESULTS: Of the 459 children, 34% were HIV
      seropositive. Their presentation was similar to HIV seronegative children but
      more were shocked on arrival at hospital (33/157 v 12/302), and more had a focus
      of infection (85/157 v 57/302). HIV positive children had a higher incidence of
      Streptococcus pneumoniae infections (52% v 32%). Sixty four cases relapsed; 67%
      were in HIV positive patients. The mortality in HIV positive children was 65%
      compared with 36% in HIV negative children. The number of survivors in each group
      was similar. Hearing loss was more common in HIV negative than HIV positive
      children (66.3% v 47.2%). Steroid therapy had no influence on meningitis in HIV
      positive children, but the mortality in HIV negative children was 61% in children
      given steroids, and 39% in those who did not receive steroids. CONCLUSION: HIV
      seropositive children who develop bacterial meningitis have a high mortality and
      are prone to recurrent disease. There is an urgent need to prevent both primary
      and recurrent infections.

PMID- 14670784
TI  - Non-invasive diagnosis of tracheobronchomalacia using a modified ventilation
      radioisotope lung scan.
AB  - The use of radionuclide ventilation lung scan to characterise the physiological
      effects of tracheobronchomalacia is a novel application of this non-invasive
      technique. In the reported case the right upper lobe was found to be not
      ventilated below a pressure of 20 cm H2O despite evidence from a dynamic
      tracheobronchogram of the right upper lobe bronchus opening at the lower pressure
      of 15 cm H2O.

PMID- 14670785
TI  - Physiological periostitis; a potential pitfall.

PMID- 14670786
TI  - Home oxygen therapy: beware of birthday cakes.

PMID- 14670787
TI  - Evidence based guidelines for the performance of the sweat test for the
      investigation of cystic fibrosis in the UK.
AB  - A well produced evidence based guideline has been developed in response to a
      national audit that demonstrated wide variations in the performance of sweat
      tests. Accurate and reliable sweat test results will be particularly important
      with the advent of neonatal screening. The guideline recommendations include the
      collection and analysis of sweat samples, and interpretation of results. It
      emphasises the importance of sweat chloride as the best discriminator.

PMID- 14670788
TI  - Population pharmacokinetics of high dose ibuprofen in cystic fibrosis.
AB  - AIMS: To evaluate ibuprofen population pharmacokinetics in a large series of data
      collected in children with cystic fibrosis (CF) treated with high doses of
      ibuprofen (59 patients; 2-18 years), and to identify the main causes responsible
      for the considerable interindividual variability in ibuprofen serum levels.
      METHODS: Blood samples were collected during routine clinical care; serum
      ibuprofen concentrations were determined by HPLC. Fitting of the
      concentration/time data to a one compartment kinetic population model was
      performed by a non-linear mixed effect regression method. RESULTS: Body weight,
      dose, and ibuprofen dosage form (lysinate salt or the free acid form), for
      elimination clearance (CL/F); and body weight, dose, and fasting status for the
      apparent distribution volume (Vd/F) proved to be the covariates with influence in
      the model. The four factors identified helped to explain part of the
      interindividual variability observed, but the remaining unexplained variability
      made therapeutic drug monitoring absolutely essential.

PMID- 14670791
TI  - Should a prolonged or short course of indomethacin be used in preterm infants to
      treat patent ductus arteriosus?

PMID- 14670792
TI  - Is indomethacin or ibuprofen better for medical closure of the patent ductus
      arteriosus?

PMID- 14670793
TI  - What is the use of the glass test?

PMID- 14670795
TI  - Infant to staff ratios and risk of mortality in very low birth weight infants.

PMID- 14670796
TI  - The use of sodium resonium in pseudohypoaldosteronism.

PMID- 14670797
TI  - Hugh Downman and smallpox inoculation.

PMID- 14670798
TI  - Once upon a time...

PMID- 14670800
TI  - Cytokine secretion by cystic fibrosis airway epithelial cells.
AB  - It is controversial whether mutations in cystic fibrosis transmembrane
      conductance regulator intrinsically dysregulate inflammation. We characterized
      passage 2 human tracheobronchial epithelial cell cultures morphologically and
      physiologically and determined whether cytokine production or nuclear factor
      kappaB activation was systematically altered in cystic fibrosis (CF) cells. Non
      CF and CF cells originating from a total of 33 and 25 lungs, respectively, were
      available for culture on plastic or at an air-liquid interface until well
      differentiated. Forskolin-stimulated short-circuit currents were present in
      representative polarized non-CF cultures and were absent in CF cultures, whereas
      uridine 5'-triphosphate-stimulated currents were present in both. Constitutive or
      interleukin (IL)-1beta-induced IL-8 or IL-6 secretion or nuclear factor-kappaB
      activity was not significantly different between non-CF and CF cells. The
      cytokines regulated upon activation, normal T cell expressed and secreted
      (RANTES) and IL-10 were not detectable. Stimulation with tumor necrosis factor
      alpha or a synthetic toll-like receptor 2 agonist or variable doses and times of
      Staphylococcus aureus culture filtrate revealed a single dose- and time-dependent
      difference in IL-8 production by CF cells. Interestingly, although IL-8 secretion
      after stimulation with Pseudomonas aeruginosa filtrates was not greater in CF
      cells in the absence of human serum, it was variably greater in its presence.
      Thus, although exaggerated responses may develop under certain conditions, our
      results do not support an overall intrinsically hyperinflammatory phenotype in CF
      cells.

PMID- 14670801
TI  - An increase of abdominal pressure increases pulmonary edema in oleic acid-induced
      lung injury.
AB  - Increased abdominal pressure is common in intensive care unit patients. To
      investigate its impact on respiration and hemodynamics we applied intraabdominal
      pressure (aIAP) of 0 and 20 cm H(2)O (pneumoperitoneum) in seven pigs. The whole
      lung computed tomography scan and a complete set of respiratory and hemodynamics
      variables were recorded both in healthy lung and after oleic acid (OA) injury. In
      healthy lung, aIAP 20 cm H(2)O significantly lowered the gas content, leaving the
      tissue content unchanged. In OA-injured lung at aIAP 0 cm H(2)O, the gas content
      significantly decreased compared with healthy lung. The excess tissue mass
      (edema) amounted to 30 +/- 24% of the original tissue weight (455 +/- 80 g). The
      edema was primarily distributed in the base regions and was not gravity
      dependent. Heart volume, central venous, pulmonary artery, wedge, and systemic
      arterial pressures significantly increased. At aIAP 20 cm H(2)O in OA-injured
      lung, the central venous and pulmonary artery pressures further increased. The
      gas content further decreased, and the excess tissue mass rose up to 103 +/- 37%
      (tissue weight 905 +/- 134 g), with homogeneous distribution along the
      cephalocaudal and sternovertebral axis. We conclude that in OA-injured lung, the
      increase of IAP increases the amount of edema.

PMID- 14670802
TI  - The predictive value of bronchiolitis obliterans syndrome stage 0-p.
AB  - Bronchiolitis obliterans syndrome (BOS) remains the main cause of graft loss
      after lung transplantation. Stage 0-p was recently added to the staging criteria
      to detect early deterioration in allograft function that might presage BOS stage
      1. We assessed the predictive value of stage 0-p by retrospectively analyzing
      spirometric data for 203 adult bilateral lung transplant recipients. The FEV(1)
      criterion for stage 0-p had a positive predictive value of 79% and a negative
      predictive value of 82%. In contrast, the FEF(25-75%) criterion for stage 0-p had
      a positive predictive value of 52% and a negative predictive value of 72%. Fifty
      seven percent of subjects who developed stage 0-p by the FEV(1) criterion
      progressed to stage 1 within 1 year, whereas only 37% of those who developed
      stage 0-p by the FEF(25-75%) criterion progressed to stage 1 within 1 year. We
      conclude that the FEV(1) criterion for stage 0-p is a reasonable predictor of BOS
      stage 1 after bilateral lung transplantation, but the FEF(25-75%) criterion for
      stage 0-p is not predictive of BOS stage 1 after bilateral lung transplantation.

PMID- 14670803
TI  - Signaling pathways regulating interleukin-13-stimulated chemokine release from
      airway smooth muscle.
AB  - Interleukin (IL)-13 receptor activation on airway smooth muscle cells induces
      eotaxin release and activates multiple signaling pathways including mitogen
      activated protein kinases, and signal transducer and activator of transcription 6
      (STAT6). To examine a requirement for STAT6 in mediating IL-13-stimulated eotaxin
      release we used antisense oligodeoxynucleotides (ODNs) to downregulate endogenous
      STAT6 protein. STAT6 antisense ODNs were taken up by about 85% of cells.
      Selective downregulation of STAT6 protein occurred with antisense ODNs, but not
      with sense or scrambled ODNs. Eotaxin release induced by IL-13 or IL-4 (10 ng/ml)
      was reduced by 81 +/- 4 and 75 +/- 7%, respectively, in cells transfected with
      antisense ODNs (p < 0.001), but not with a sense ODN or a scrambled ODN. Eotaxin
      release induced by IL-1beta was unaffected by STAT6 antisense ODN (p > 0.05).
      Finally, IL-13- or IL-4-dependent eotaxin release was abolished when inhibitors
      of both p42/p44 ERK (U0126, 10 microM) and p38 (SB202190, 10 microM) mitogen
      activated protein kinase pathways were combined in STAT6 antisense ODN
      transfected cells. In contrast, about 25% of the response remained when each
      inhibitor was examined alone in STAT6 antisense ODN-treated cells. These data
      support roles for both STAT6- and mitogen-activated protein kinase-dependent
      pathways in mediating eotaxin release from airway smooth muscle by IL-13 or IL-4.

PMID- 14670804
TI  - Preferential diaphragmatic weakness during sustained Pseudomonas aeruginosa lung
      infection.
AB  - Infection with Pseudomonas aeruginosa plays a major role in the pulmonary
      inflammation and injury associated with cystic fibrosis. Lung inflammation may
      also lead to more widespread systemic effects on other organs. We tested the
      following hypotheses: (1) ongoing P. aeruginosa lung infection produces
      diaphragmatic and limb muscle weakness and (2) such muscle dysfunction is
      directly correlated with the level of pulmonary inflammation. Chronic
      bronchopulmonary infection with mucoid P. aeruginosa was induced in C57BL/6 mice.
      At Day 2 after infection, diaphragmatic force was decreased (37%) only in mice
      infected with a high dose of 1 x 10(6) cfu, whereas by Day 7 after infection,
      diaphragmatic force was similarly reduced (36%) even at a fivefold lower
      inoculating dose. No significant correlations were found between diaphragmatic
      weakness and pulmonary inflammation, as assessed by the number of neutrophils,
      macrophages, and lymphocytes in bronchoalveolar lavage fluid. Moreover, in marked
      contrast to the diaphragm, no effects of P. aeruginosa infection on contractile
      function were observed in prototypical slow- and fast-twitch hindlimb muscles. We
      conclude that sustained lung infection with P. aeruginosa induces preferential
      weakness of the diaphragm, which is not directly correlated with the degree of
      pulmonary inflammation induced under these conditions.

PMID- 14670805
TI  - Adult cystic fibrosis exacerbations and new strains of Pseudomonas aeruginosa.
AB  - We hypothesized that in adults with cystic fibrosis, the acquisition of a new
      strain of Pseudomonas aeruginosa may be associated with a pulmonary exacerbation.
      Eighty-four patients who were chronically infected with P. aeruginosa were
      prospectively followed from eight centers over a 26-month period. Patients had
      sputum cultures performed every 3 months while clinically stable and at the time
      of an exacerbation. Forty patients (48%) had an exacerbation requiring
      intravenous antibiotics during the study period, and in 36 of these patients,
      their P. aeruginosa isolates were genetically typeable by pulsed-field gel
      electrophoresis. In 34 of the 36 patients (94%), P. aeruginosa recovered during
      clinical stability and at exacerbation were of the same genotype. In only two
      patients (6%; 95% confidence interval, 0-18%) was a new P. aeruginosa clone
      cultured during an exacerbation that had not been cultured during clinical
      stability. There were no significant differences in antibiotic susceptibilities,
      measured as mean minimal inhibitory concentrations, for isolates retrieved during
      clinically stable periods compared with isolates retrieved during exacerbations.
      We conclude that for the majority of adult patients with cystic fibrosis a new
      pulmonary exacerbation is not caused by the acquisition of a new strain of P.
      aeruginosa.

PMID- 14670806
TI  - Changes in dietary sodium consumption modulate GLUT4 gene expression and early
      steps of insulin signaling.
AB  - Previous studies have shown that chronic salt overload increases insulin
      sensitivity, while chronic salt restriction decreases it. In the present study we
      investigated the influence of dietary sodium on 1) GLUT4 gene expression, by No
      the n and Western blotting analysis; 2) in vivo GLUT4 protein translocation, by
      measuring the GLUT4 protein in plasma membrane and microsome, before and after
      insulin injection; and 3) insulin signaling, by analyzing basal and insulin
      stimulated tyrosine phosphorylation of insulin receptor (IR)-beta, insulin
      receptor substrate (IRS)-1, and IRS-2. Wistar rats we e fed no mal-sodium (NS
      0.5%), low-sodium (LS-0.06%), o high-sodium diets (HS-3.12%) fo 9 wk and were
      killed under pentobarbital anesthesia. Compared with NS ats, HS ats inc eased (P
      < 0.05) the GLUT4 protein in adipose tissue and skeletal muscle, whereas GLUT4
      mRNA was increased only in adipose tissue. GLUT4 expression was unchanged in LS
      ats compared with NS ats. The GLUT4 translocation in HS ats was higher (P < 0.05)
      both in basal and insulin-stimulated conditions. On the other hand, LS ats did
      not increase the GLUT4 translocation after insulin stimulus. Compared with NS
      ats, LS ats showed reduced (P < 0.01) basal and insulin-stimulated tyrosine
      phosphorylation of IRS-1 in skeletal muscle and IRS-2 in live, whereas HS ats
      showed enhanced basal tyrosine phosphorylation of IRS-1 in skeletal muscle (P <
      0.05) and of IRS-2 in live. In summary, increased insulin sensitivity in HS ats
      is elated to increased GLUT4 gene expression, enhanced insulin signaling, and
      GLUT4 translocation, whereas decreased insulin sensitivity of LS ats does not
      involve changes in GLUT4 gene expression but is elated to impaired insulin
      signaling.

PMID- 14670807
TI  - Loss of vasomotor responsiveness to the mu-opioid receptor ligand endomorphin-1
      in adjuvant monoarthritic rat knee joints.
AB  - Endomorphin-1 is a short-chain neuropeptide with a high affinity fo the mu-opioid
      receptor and has recently been localized in acutely inflamed knee joints where it
      was found to reduce inflammation. The present study examined the propensity of
      endomorphin-1 to modulate synovial blood flow in normal and adjuvant-inflamed at
      knee joints. Under deep urethane anesthesia, endomorphin-1 was topically applied
      to exposed normal and 1 wk adjuvant monoarthritic knee joints (0.1 ml bolus; 10(
      12)-10(-9) mol). Relative changes in articular blood flow were measured by laser
      Doppler perfusion imaging and vascular resistances in response to the opioid were
      calculated. In normal knees, endomorphin-1 caused a dose-dependent increase in
      synovial vascular resistance and this effect was significantly inhibited by the
      specific mu-opioid receptor antagonist d-Phe-Cys-Tyr-d-Trp-O n-Thr-Pen-Th amide
      (CTOP) (P < 0.0001, 2-factor ANOVA, n = 5-7). One week after adjuvant
      inflammation, the hypoaemic effect of endomorphin-1 was completely abolished (P <
      0.0001, 2-factor ANOVA, n = 5-7). Immunohistochemical analysis of normal and
      adjuvant-inflamed joints showed a ninefold increase in endomorphin-1 levels in
      the monoarthritic knee compared with normal control. Western blotting and
      immunohistochemistry revealed a moderate number of mu-opioid receptors in normal
      knees; however, mu-opioid receptors were almost undetectable in arthritic joints.
      These findings demonstrate that peripheral administration of endomorphin-1
      reduces knee joint blood flow and this effect is not sustainable during advanced
      inflammation. The loss of this hypoaemic response appears to be due to down
      regulation of mu-opioid receptors as a consequence of endomorphin-1 accumulation
      within the arthritic joint.

PMID- 14670808
TI  - Acute inhibition of the hypothalamic paraventricular nucleus decreases renal
      sympathetic nerve activity and arterial blood pressure in water-deprived rats.
AB  - The present study was performed to determine whether sympathetic outflow and
      arterial blood pressure in water-deprived rats are dependent on the ongoing
      neuronal activity of the hypothalamic paraventricular nucleus (PVN). Renal
      sympathetic nerve activity (RSNA), mean arterial blood pressure (MAP), and heart
      rate were recorded in urethane-alpha-chloralose-anesthetized rats that were
      deprived of water but not food for 48 h before experiments. Acute inhibition of
      the PVN by bilateral microinjection of the GABA(A) agonist muscimol (100
      pmol/side) significantly decreased RSNA in water-deprived rats (-26.7 +/- 4.7%, n
      = 7) but was without effect in control rats (1.3 +/- 6.3%, n = 7). Similarly,
      injection of muscimol produced a greater decrease in MAP in water-deprived rats
      than in control rats (-46 +/- 3 vs. -16 +/- 3 mmHg, respectively), although
      baseline MAP was not different between groups (105 +/- 4 vs. 107 +/- 4 mmHg,
      respectively). Neither bilateral microinjection of isotonic saline vehicle (100
      nl/side) into the PVN nor muscimol (100 pmol/side) outside the PVN altered RSNA
      or MAP in either group. In addition, ganglionic blockade with hexamethonium (30
      mg/kg i.v.) significantly decreased MAP in both groups; however, the decrease in
      MAP was significantly greater in water-deprived rats than in control rats (62 +/-
      2 vs. 48 +/- 2 mmHg, respectively). Collectively, these findings suggest that
      sympathetic outflow contributes more to the maintenance of blood pressure in the
      water-deprived rat, and this depends, at least partly, on the ongoing activity of
      PVN neurons.

PMID- 14670809
TI  - High levels of myocardial antioxidant defense in aging nondiabetic normotensive
      Zucker obese rats.
AB  - Chronic renal failure often induces left ventricular hypertrophy. We assessed
      whether the heart is affected in the Zucker obese rat, a model of chronic renal
      failure associated with obesity, glucose intolerance, and insulin resistance
      without hypertension or hyperglycemia. After systemic blood pressure measurement,
      the heart, the aorta, and the kidneys were removed from anesthetized 9- and 13-mo
      old Zucker obese and lean control male rats (n = 33, n = 24, n = 25, and n = 21,
      respectively). Determination of left ventricular geometry, quantification of
      myocardium collagen density, and measurement of heart antioxidant enzyme activity
      were made, as well as aorta and kidney parameters. Mean blood pressure remained
      at a normal range whatever the age and group considered. Whereas kidney structure
      and function were severely impaired, no sign of myocardial infarction or
      inflammatory process was noticed. A moderate left ventricular hypertrophy was
      observed in 13-mo-old obese rats. While heart malondialdehyde was stable with age
      and among groups, antioxidant enzyme activity was higher in obese rats. In
      conclusion, in the absence of hypertensive or hyperglycemic disorders, the heat
      seems to display a sufficient line of defense against oxidative stress during the
      development of cardiac hypertrophy.

PMID- 14670810
TI  - Acipimox enhances spontaneous growth hormone secretion in obese women.
AB  - We hypothesized that a high circulating free fatty acid (FFA) concentration is
      involved in the pathogenesis of hyposomatotropism associated with obesity. To
      evaluate this hypothesis, 10 healthy premenopausal women (body mass index 33.8 +/
      1.0 kg/m(2)) were studied in the follicular phase of their menstrual cycle at
      two occasions with a time interval of at least 8 wk, where body weight remained
      stable. Subjects were randomly assigned to treatment with either acipimox (an
      inhibitor of lipolysis, 250 mg orally 4 times daily) or placebo in a double-blind
      crossover design, starting 1 day before admission until the end of the blood
      sampling period. Blood samples were taken during 24 h with a sampling interval of
      10 min for assessment of growth hormone (GH) concentrations, and GH secretion was
      estimated by deconvolution analysis. Identical methodology was used to study GH
      secretion in a historical control group of age-matched normal weight women. GH
      secretion was clearly blunted in obese women (total daily release 66 +/- 10 vs.
      lean controls: 201 +/- 23 mU x l(Vd)(-1) x 24 h(-1), P = 0.005, where l(Vd) is
      lite of distribution volume). Acipimox considerably enhanced total (113 +/- 50
      vs. 66 +/- 10 mU x l(Vd)(-1) x 24 h(-1), P = 0.02) and pulsatile GH secretion
      (109 +/- 49 vs. 62 +/- 30 mU x l(Vd)(-1) x 24 h(-1), P = 0.02), but GH output
      remained lower compared with lean controls. Further analysis did not show any
      relationship between the effects of acipimox on GH secretion and regional body
      fat distribution. In conclusion, acipimox unleashes spontaneous GH secretion in
      obese women. It specifically enhances GH secretory burst mass. This might mean
      that lowering of systemic FFA concentrations by acipimox modulates neuroendocrine
      mechanisms that orchestrate the activity of the somatotropic ensemble.

PMID- 14670811
TI  - Pattern differences between distributions of microregional myocardial flows in
      crystalloid- and blood-perfused rat hearts.
AB  - Regional myocardial flow distributions in Langendorff rat hearts under Tyrode and
      blood perfusion were assessed by tracer digital radiography (100-microm
      resolution). Flow distributions during baseline and maximal hyperemia following a
      60-s flow cessation were evaluated by the coefficient of variation of regional
      flows (CV; related to global flow heterogeneity) and the correlation between
      adjacent regional flows (CA; inversely related to local flow randomness). These
      values were obtained for the original images (64(2) pixels) and for coarse
      grained images (32(2), 16(2), and 8(2) blocks of nearby pixels). At a given point
      in time during baseline, both CV and CA were higher in blood (n = 7) than in
      Tyrode perfusion (n = 7) over all pixel aggregates (P < 0.05, two-way ANOVA).
      During the maximal hyperemia, CV and CA were still significantly higher in blood
      (n = 7) than in Tyrode perfusion (n = 7); however, these values decreased
      substantially in blood perfusion and the CV and CA differences became smaller
      than those at baseline accordingly. During basal blood perfusion, the 60-s
      average flow distribution (n = 7) showed a smaller CV and CA than those at a
      given point in time (P < 0.05, two-way ANOVA). Coronary flow reserve was
      significantly higher in blood than in Tyrode perfusion. In conclusion, the flow
      heterogeneity and the local flow similarity are both higher in blood than in
      Tyrode perfusion, probably due to the different degree of coronary tone
      preservation and the presence or absence of blood corpuscles. Under blood
      perfusion, temporal flow fluctuations over 60-s order are largely involved in
      shaping microregional flow distributions.

PMID- 14670812
TI  - Inhibition of cyclooxygenase-2 improves cardiac function after myocardial
      infarction in the mouse.
AB  - Cyclooxygenase (COX)-2 is expressed in the heart in animal models of ischemic
      injury. Recent studies have suggested that COX-2 products are involved in
      inflammatory cell infiltration and fibroblast proliferation in the heart. Using a
      mouse model, we questioned whether 1). myocardial infarction (MI) in vivo induces
      COX-2 expression chronically, and 2). COX-2 inhibition reduces collagen content
      and improves cardiac function in mice with MI. MI was produced by ligation of the
      left anterior descending coronary artery in mice. Two days later, mice were
      treated with 3 mg/kg NS-398, a selective COX-2 inhibitor, or vehicle in drinking
      water for 2 wk. After the treatment period, mice were subjected to two
      dimensional M-mode echocardiography to determine cardiac function. Hearts were
      then analyzed for determination of infarct size, interstitial collagen content,
      brain natriuretic peptide (BNP) mRNA, myocyte cross-sectional area, and
      immunohistochemical staining for transforming growth factor (TGF)-beta and COX-2.
      COX-2 protein, detected by immunohistochemistry, was increased in MI versus sham
      hearts. MI resulted in increased left ventricular systolic and diastolic
      dimension and decreased ejection fraction, fractional shortening, and cardiac
      output. NS-398 treatment partly reversed these detrimental changes. Myocyte cross
      sectional area, a measure of hypertrophy, was decreased by 30% in the NS-398
      versus vehicle group, but there was no effect on BNP mRNA. The interstitial
      collagen fraction increased from 5.4 +/- 0.4% in sham hearts to 10.4 +/- 0.9% in
      MI hearts and was decreased to 7.9 +/- 0.6% in NS-398-treated hearts. A second
      COX-2 inhibitor, rofecoxib (MK-0966), also decreased myocyte cross-sectional area
      and interstitial collagen fraction. TGF-beta, a key regulator of collagen
      synthesis, was increased in MI hearts. NS-398 treatment reduced TGF-beta
      immunostaining by 40%. NS-398 treatment had no effect on infarct size. These
      results suggest that COX-2 products contribute to cardiac remodeling and
      functional deficits after MI. Thus selected inhibition of COX-2 may be a
      therapeutic target for reducing myocyte damage after MI.

PMID- 14670813
TI  - Subcellular localization of the delayed rectifier K(+) channels KCNQ1 and ERG1 in
      the rat heart.
AB  - In the heart, several K(+) channels are responsible for the repolarization of the
      cardiac action potential, including transient outward and delayed rectifier K(+)
      currents. In the present study, the cellular and subcellular localization of the
      two delayed rectifier K(+) channels, KCNQ1 and ether-a-go-go-related gene-1
      (ERG1), was investigated in the adult rat heart. Confocal immunofluorescence
      microscopy of atrial and ventricular cells revealed that whereas KCNQ1 labeling
      was detected in both the peripheral sarcolemma and a structure transversing the
      myocytes, ERG1 immunoreactivity was confined to the latter. Immunoelectron
      microscopy of atrial and ventricular myocytes showed that the ERG1 channel was
      primarily expressed in the transverse tubular system and its entrance, whereas
      KCNQ1 was detected in both the peripheral sarcolemma and in the T tubules. Thus,
      whereas ERG1 displays a very restricted subcellular localization pattern, KCNQ1
      is more widely distributed within the cardiac cells. The localization of these
      K(+) channels to the transverse tubular system close to the Ca(2+) channels
      renders them with maximal repolarizing effect.

PMID- 14670814
TI  - Impaired function of alpha2-adrenergic autoreceptors on sympathetic nerves
      associated with mesenteric arteries and veins in DOCA-salt hypertension.
AB  - The present study tested the hypothesis that there is impaired function of
      alpha(2)-adrenergic autoreceptors and increased transmitter release from
      sympathetic nerves associated with mesenteric arteries and veins from DOCA-salt
      rats. High-performance liquid chromatography was used to measure the overflow of
      ATP and norepinephrine (NE) from electrically stimulated mesenteric artery and
      vein preparations in vitro. In sham arteries, nerve stimulation evoked a 1.5-fold
      increase in NE release, whereas in DOCA-salt arteries there was a 3.9-fold
      increase in NE release over basal levels (P < 0.05). In contrast, stimulated ATP
      release was not different in DOCA-salt arteries compared with sham arteries. In
      sham veins, nerve stimulation evoked a 2.9-fold increase in NE release, whereas
      in DOCA-salt veins there was a 8.4-fold increase in NE release over basal levels
      (P < 0.05). In sham rats NE release, normalized to basal levels, was greater in
      veins than in arteries (P < 0.05). The alpha(2)-adrenergic receptor antagonist
      yohimbine (1 microM) increased ATP and NE release in sham but not DOCA-salt
      arteries. The alpha(2)-adrenergic receptor agonist UK-14304 (10 microM) decreased
      ATP release in sham but not DOCA-salt arteries. In sham veins, UK-14304
      decreased, but yohimbine increased, NE release; effects that were not observed in
      DOCA-salt veins. These data show that nerve stimulation causes a greater increase
      in NE release from nerves associated with veins compared with arteries. In
      addition, impairment of alpha(2)-adrenergic autoreceptor function in sympathetic
      nerves associated with arteries and veins from DOCA-salt rats results in
      increased NE release.

PMID- 14670815
TI  - Relationship between arterial diameter and perfused tissue volume in myocardial
      microcirculation: a micro-CT-based analysis.
AB  - The volume of myocardial tissue that is perfused by an epicardial coronary artery
      has been shown to be predictably related to the diameter of the epicardial
      arterial lumen. However, to what extent the intramyocardial microvasculature
      follows the epicardial rules remains unclear. To explore the relationship between
      the diameter of coronary arterioles and their subsequent perfused myocardial
      volumes, we quantified the volume of nonperfused myocardium resulting from an
      embolized arteriole of a certain diameter. We injected a single dose of
      microspheres selected from one of nine possible microsphere combinations (10, 30,
      and 100 microm diameter, each at three possible doses) into the left anterior
      descending coronary and/or left circumflex arteries of seven anesthetized pigs.
      At postmortem, the coronary arteries were infused with a radiopaque silicon
      polymer. Embolized myocardium (1 cm(3)) was scanned with a microcomputerized
      tomography scanner and resulted in three-dimensional images that consisted of 20
      microm/side cubic voxels and a subvolume of the specimen with 4 microm/side cubic
      voxels. Image analysis provided the number and volumes of myocardial perfusion
      defects for each size and dose of microspheres. The smallest individual
      myocardial perfusion defects, which correspond to the volume of myocardium
      perfused by a single embolized arteriole, were found to be 0.0004 +/- 0.0002,
      0.02 +/- 0.004, and 0.62 +/- 0.099 mm(3) for the 10-, 30-, and 100-microm
      microspheres, respectively. The number of myocardial perfusion defects in the
      embolized myocardium was inversely related to the dose of the injected
      microspheres. This reflects a clustering behavior that is consistent with a
      random distribution process of the individual embolized perfusion defects.

PMID- 14670816
TI  - Mechanisms of postspaceflight orthostatic hypotension: low alpha1-adrenergic
      receptor responses before flight and central autonomic dysregulation postflight.
AB  - Although all astronauts experience symptoms of orthostatic intolerance after
      short-duration spaceflight, only approximately 20% actually experience presyncope
      during upright posture on landing day. The presyncopal group is characterized by
      low vascular resistance before and after flight and low norepinephrine release
      during orthostatic stress on landing day. Our purpose was to determine the
      mechanisms of the differences between presyncopal and nonpresyncopal groups. We
      studied 23 astronauts 10 days before launch, on landing day, and 3 days after
      landing. We measured pressor responses to phenylephrine injections;
      norepinephrine release with tyramine injections; plasma volumes; resting plasma
      levels of chromogranin A (a marker of sympathetic nerve terminal release),
      endothelin, dihydroxyphenylglycol (DHPG, an intracellular metabolite of
      norepinephrine); and lymphocyte beta(2)-adrenergic receptors. We then measured
      hemodynamic and neurohumoral responses to upright tilt. Astronauts were separated
      into two groups according to their ability to complete 10 min of upright tilt on
      landing day. Compared with astronauts who were not presyncopal on landing day,
      presyncopal astronauts had 1). significantly smaller pressor responses to
      phenylephrine both before and after flight; 2). significantly smaller baseline
      norepinephrine, but significantly greater DHPG levels, on landing day; 3).
      significantly greater norepinephrine release with tyramine on landing day; and
      4). significantly smaller norepinephrine release, but significantly greater
      epinephrine and arginine vasopressin release, with upright tilt on landing day.
      These data suggest that the etiology of orthostatic hypotension and presyncope
      after spaceflight includes low alpha(1)-adrenergic receptor responsiveness before
      flight and a remodeling of the central nervous system during spaceflight such
      that sympathetic responses to baroreceptor input become impaired.

PMID- 14670817
TI  - Transmural heterogeneity of calcium activity and mechanical function in the
      canine left ventricle.
AB  - Although electrical heterogeneity within the ventricular myocardium has been the
      focus of numerous studies, little attention has been directed to the mechanical
      correlates. This study examines unloaded cell shortening, Ca(2+) transients, and
      inward L-type Ca(2+) current (I(Ca,L)) characteristics of epicardial,
      endocardial, and midmyocardial cells isolated from the canine left ventricle.
      Unloaded cell shortening was recorded using a video edge detector, Ca(2+)
      transients were measured in cells loaded with 15 microM fluo-3 AM and voltage and
      current-clamp recordings were obtained using patch-clamp techniques. Time to peak
      and latency to onset of contraction were shortest in epicardial and longest in
      endocardial cells; midmyocardial cells displayed an intermediate time to peak.
      When contraction was elicited using uniform voltage-clamp square waves,
      epicardial versus endocardial distinctions persisted and midmyocardial cells
      displayed a time to peak comparable to that of epicardium. The current-voltage
      relationship for I(Ca,L) and fluorescence-voltage relationship were similar in
      the three cell types when quantitated using square pulses. However, peak I(Ca,L)
      and total charge were significantly larger when an epicardial versus endocardial
      action potential waveform was used to elicit the current under voltage-clamp
      conditions. Sarcoplasmic reticulum Ca(2+) content, assessed by rapid application
      of caffeine, was largest in epicardial cells and contributed to a faster time to
      peak. Our data point to important differences in calcium homeostasis and
      mechanical function among the three ventricular cell types. These differences
      serve to synchronize contraction across the ventricular wall. Although these
      distinctions are conferred in part by differences in electrical characteristics
      of the three cell types, intrinsic differences in excitation-contraction coupling
      are evident.

PMID- 14670818
TI  - Senescence alters blood flow responses to acute heat stress.
AB  - Renal and splanchnic sympathetic nerve discharge (SND) responses to heating are
      significantly reduced in senescent compared with young Fischer-344 (F344) rats
      (Kenney MJ and Fels RJ. Am J Physiol Regul Integr Comp Physiol 283: R513-R520,
      2002). However, the functional significance of this finding is not known. We
      tested the hypothesis that blood flow distribution profiles to heating are
      altered in senescent (24 mo old) compared with mature (12 mo old) and young (3 mo
      old) F344 rats. Visceral organ, skeletal muscle, and tail blood flows were
      determined with the radionuclide-tagged microsphere technique before (control, 38
      degrees C) and during heating that increased body temperature to 41 degrees C in
      anesthetized F344 rats. Vascular conductance in the kidney, stomach, large
      intestine, pancreas, spleen, and tail was significantly reduced during control
      before heating in senescent compared with young F344 rats. Heating significantly
      decreased kidney, stomach, small and large intestine, and pancreas vascular
      conductance in young and mature but not senescent F344 rats. Vascular conductance
      at 41 degrees C in the kidney and small intestine was significantly lower and in
      the stomach tended to be lower in young compared with senescent rats. Splenic
      conductance increased during heating in young and senescent rats but was highest
      in young rats. Tail conductance during heating was significantly increased in
      young rats but remained unchanged in mature and senescent rats. These results
      demonstrate a marked attenuation in heating-induced vascular conductance changes
      in senescent rats, suggesting an important functional consequence for the
      attenuated SND responses to heating in aged rats.

PMID- 14670819
TI  - Profiling substrate fluxes in the isolated working mouse heart using 13C-labeled
      substrates: focusing on the origin and fate of pyruvate and citrate carbons.
AB  - The availability of genetically modified mice requires the development of methods
      to assess heart function and metabolism in the intact beating organ. With the use
      of radioactive substrates and ex vivo perfusion of the mouse heart in the working
      mode, previous studies have documented glucose and fatty acid oxidation pathways.
      This study was aimed at characterizing the metabolism of other potentially
      important exogenous carbohydrate sources, namely, lactate and pyruvate. This was
      achieved by using (13)C-labeling methods. The mouse heart perfusion setup and
      buffer composition were optimized to reproduce conditions close to the in vivo
      milieu in terms of workload, cardiac functions, and substrate-hormone supply to
      the heart (11 mM glucose, 0.8 nM insulin, 50 microM carnitine, 1.5 mM lactate,
      0.2 mM pyruvate, 5 nM epinephrine, 0.7 mM oleate, and 3% albumin). The use of
      three differentially (13)C-labeled carbohydrates and a (13)C-labeled long-chain
      fatty acid allowed the quantitative assessment of the metabolic origin and fate
      of tissue pyruvate as well as the relative contribution of substrates feeding
      acetyl-CoA (pyruvate and fatty acids) and oxaloacetate (pyruvate) for
      mitochondrial citrate synthesis. Beyond concurring with the notion that the mouse
      heart preferentially uses fatty acids for energy production (63.5 +/- 3.9%) and
      regulates its fuel selection according to the Randle cycle, our study reports for
      the first time in the mouse heart the following findings. First, exogenous
      lactate is the major carbohydrate contributing to pyruvate formation (42.0 +/-
      2.3%). Second, lactate and pyruvate are constantly being taken up and released by
      the heart, supporting the concept of compartmentation of lactate and glucose
      metabolism. Finally, mitochondrial anaplerotic pyruvate carboxylation and citrate
      efflux represent 4.9 +/- 1.8 and 0.8 +/- 0.1%, respectively, of the citric acid
      cycle flux and are modulated by substrate supply. The described (13)C-labeling
      strategy combined with an experimental setup that enables continuous monitoring
      of physiological parameters offers a unique model to clarify the link between
      metabolic alterations, cardiac dysfunction, and disease development.

PMID- 14670820
TI  - Differential regulation of activator protein-1 and heat shock factor-1 in
      myocardial ischemia and reperfusion injury: role of poly(ADP-ribose) polymerase
      1.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme activated in response to
      DNA strand breaks, has been implicated in cell dysfunction in myocardial
      reperfusion injury. PARP-1 has also been shown to participate in transcription
      and regulation of gene expression. In this study, we investigated the role of
      PARP-1 on the signal transduction pathway of activator protein-1 (AP-1) and heat
      shock factor-1 (HSF-1) in myocardial reperfusion injury. Mice genetically
      deficient of PARP-1 (PARP-1(-/-) mice) exhibited a significant reduction of
      myocardial damage after occlusion and reperfusion of the left anterior descending
      branch of the coronary artery compared with their wild-type littermates. This
      cardioprotection was associated with a reduction of the phosphorylative activity
      of JNK and, subsequently, reduction of the DNA binding of the signal transduction
      factor AP-1. On the contrary, in PARP-1(-/-) mice, DNA binding of HSF-1 was
      enhanced and was associated with a significant increase of the cardioprotective
      heat shock protein (HSP)70 compared with wild-type mice. Microarray analysis
      revealed that expression of several AP-1-dependent genes of proinflammatory
      mediators and HSPs was altered in PARP-1(-/-) mice. The data indicate that PARP-1
      may exert a pathological role in reperfusion injury by functioning as an
      enhancing factor of AP-1 activation and as a repressing factor of HSF-1
      activation and HSP70 expression.

PMID- 14670821
TI  - Chronic allergy to dietary ovalbumin induces lymphocyte migration to rat small
      intestinal mucosa that is inhibited by MAdCAM-1.
AB  - Few models have described a chronic food allergy with morphological changes in
      the intestinal mucosa. Here we established an ovalbumin (OVA)-induced, cell
      mediated, allergic rat model and examined lymphocyte migration in the gut. Brown
      Norway rats were intraperitoneally sensitized to OVA and then given 10 mg OVA/day
      by gastric intubation for 6 wk. Lymphocyte subsets and adhesion molecules were
      examined immunohistochemically, and the migration of T lymphocytes to
      microvessels of Peyer's patches and villus mucosa was observed by using an
      intravital microscope. Serum OVA-specific IgG and IgE levels were increased in
      animals repeatedly exposed to OVA. Significant villus atrophy and increased crypt
      depth was accompanied by increased infiltration of T lymphocytes in the small
      intestinal mucosa of the group given OVA. Expression of rat mast cell protease II
      and of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) was also increased
      in these groups. The administration of anti-MAdCAM-1 antibody significantly
      attenuated the OVA-induced changes in the mucosal architecture and in CD4 T
      lymphocyte infiltration. Intravital observation demonstrated that in rats with a
      chronic allergy, T lymphocytes significantly accumulated in villus microvessels
      as well as in Peyer's patches via a MAdCAM-1-dependent process. Our model of
      chronic food allergy revealed that lymphocyte migration was increased with MAdCAM
      1 upregulation.

PMID- 14670822
TI  - Oxidative modification of hepatic mitochondria protein thiols: effect of chronic
      alcohol consumption.
AB  - Redox modification of mitochondrial proteins is thought to play a key role in
      regulating cellular function, although direct evidence to support this hypothesis
      is limited. Using an in vivo model of mitochondrial redox stress, ethanol
      hepatotoxicity, the modification of mitochondrial protein thiols was examined
      using a proteomics approach. Specific labeling of reduced thiols in the
      mitochondrion from the livers of control and ethanol-fed rats was achieved by
      using the thiol reactive compound (4-iodobutyl)triphenylphosphonium (IBTP). This
      molecule selectively accumulates in the organelle and can be used to identify
      thiol-containing proteins. Mitochondrial proteins that have been modified are
      identified by decreased labeling with IBTP using two-dimensional SDS-PAGE
      followed by immunoblotting with an antibody directed against the
      triphenylphosphonium moiety of the IBTP molecule. Analyses of these data showed a
      significant decrease in IBTP labeling of thiols present in specific mitochondria
      matrix proteins from ethanol-fed rats compared with their corresponding controls.
      These proteins were identified as the low-K(m) aldehyde dehydrogenase and glucose
      regulated protein 78. The decrease in IBTP labeling in aldehyde dehydrogenase was
      accompanied by a decrease in specific activity of the enzyme. These data
      demonstrate that mitochondrial protein thiol modification is associated with
      chronic alcohol intake and might contribute to the pathophysiology associated
      with hepatic injury. Taken together, we have developed a protocol to chemically
      tag and select thiol-modified proteins that will greatly enhance efforts to
      establish posttranslational redox modification of mitochondrial protein in in
      vivo models of oxidative or nitrosative stress.

PMID- 14670823
TI  - Hydrogen peroxide contributes to motor dysfunction in ulcerative colitis.
AB  - Ulcerative colitis (UC) affects colonic motor function, but the mechanism
      responsible for this motor dysfunction is not well understood. We have shown that
      neurokinin A (NKA) may be an endogenous neurotransmitter mediating contraction of
      human sigmoid colonic circular muscle (HSCCM). To elucidate factors responsible
      for UC motor dysfunction, we examined the role of hydrogen peroxide (H(2)O(2)) in
      the decrease of NKA-induced response of HSCCM. As previously demonstrated, NKA
      induced contraction or Ca(2+) increase of normal muscle cells is mediated by
      release of Ca(2+) from intracellular stores, because it was not affected by
      incubation in Ca(2+)-free medium (CFM) containing 200 microM BAPTA. In UC,
      however, CFM reduced both cell contraction and NKA-induced Ca(2+) increase,
      suggesting reduced Ca(2+) release from intracellular stores. In normal Ca(2+)
      medium, NKA and KCl caused normal Ca(2+) signal in UC cells but reduced cell
      shortening. The decreased Ca(2+) signal and contraction in response to NKA or
      thapsigargin were partly recovered in the presence of H(2)O(2) scavenger
      catalase, suggesting involvement of H(2)O(2) in UC-induced dysmotility. H(2)O(2)
      levels were higher in UC than in normal HSCCM, and enzymatically isolated UC
      muscle cells contained much higher levels of H(2)O(2) than normal cells, which
      were significantly reduced by catalase. H(2)O(2) treatment of normal cells in CFM
      reproduced the reduction of NKA-induced Ca(2+) release observed in UC cells. In
      addition, H(2)O(2) caused a measurable, direct release of Ca(2+) from
      intracellular stores. We conclude that H(2)O(2) may contribute to reduction of
      NKA-induced Ca(2+) release from intracellular Ca(2+) stores in UC and contribute
      to the observed colonic motor dysfunction.

PMID- 14670824
TI  - Treatment of EFA deficiency with dietary triglycerides or phospholipids in a
      murine model of extrahepatic cholestasis.
AB  - Essential fatty acid (EFA) deficiency during cholestasis is mainly due to
      malabsorption of dietary EFA (23). Theoretically, dietary phospholipids (PL) may
      have a higher bioavailability than dietary triglycerides (TG) during cholestasis.
      We developed murine models for EFA deficiency (EFAD) with and without
      extrahepatic cholestasis and compared the efficacy of oral supplementation of EFA
      as PL or as TG. EFAD was induced in mice by feeding a high-fat EFAD diet. After 3
      wk on this diet, bile duct ligation was performed in a subgroup of mice to
      establish extrahepatic cholestasis. Cholestatic and noncholestatic EFAD mice
      continued on the EFAD diet (controls) or were supplemented for 3 wk with EFA-rich
      TG or EFA-rich PL. Fatty acid composition was determined in plasma, erythrocytes,
      liver, and brain. After 4 wk of EFAD diet, induction of EFAD was confirmed by a
      sixfold increased triene-to-tetraene ratio (T/T ratio) in erythrocytes of
      noncholestatic and cholestatic mice (P < 0.001). EFA-rich TG and EFA-rich PL were
      equally effective in preventing further increase of the erythrocyte T/T ratio,
      which was observed in cholestatic and noncholestatic nonsupplemented mice (12-
      and 16-fold the initial value, respectively). In cholestatic mice, EFA-rich PL
      was superior to EFA-rich TG in decreasing T/T ratios of liver TG and PL (each P <
      0.05) and in increasing brain PL concentrations of the long-chain polyunsaturated
      fatty acids (LCPUFA) docosahexaenoic acid and arachidonic acid (each P < 0.05).
      We conclude that oral EFA supplementation in the form of PL is more effective
      than in the form of TG in increasing LCPUFA concentrations in liver and brain of
      cholestatic EFAD mice.

PMID- 14670825
TI  - Parallel detection of autoantibodies with microarrays in rheumatoid diseases.
AB  - BACKGROUND: Clinical needs often dictate testing for several autoantibodies in a
      single patient with evidence of autoimmune disease. We developed a microarray
      containing 15 autoantigens for the detection of autoantibodies in rheumatoid
      autoimmune diseases. METHODS: We synthesized recombinant centromere protein B,
      cytokeratin 19, SSA 52-kDa antigen, SSA 60-kDa antigen, SSB antigen, and Jo-1
      antigen and prepared anti-nuclear antibody antigens. Cyclic citrullinated
      peptide, histone, goat IgG for detection of rheumatoid factor, double-stranded
      DNA, and single-stranded DNA were purchased, as were recombinant small nuclear
      ribonucleoprotein U1, topoisomerase I, and Smith antigen (Sm). All 15 antigens
      were of human origin except calf thymus Sm. Proteins were printed on polystyrene.
      The arrays were incubated with serum samples and then with horseradish peroxidase
      conjugated secondary antibodies and chemiluminescent substrates, and light
      signals were captured by a charge-coupled device camera-based chip reader.
      Antibodies were quantified by use of calibration curves. Positive samples were
      confirmed by commercially available methods. RESULTS: The detection limit of the
      microarray system was 20 pg of IgG printed on the polystyrene support. More than
      85% of the confirmed positive sera were detected as positive with the microarray
      system based on cutoff values established with the microarray system. The
      imprecision (CV) of the microarrays was <15% for all 15 autoantibody assays, with
      the exception of single-stranded DNA (18% and 23%) within and between batches.
      Characteristic autoantibody patterns were seen in patients with clinical
      diagnoses of rheumatoid arthritis (n = 83), systemic lupus erythematosus (n =
      71), systemic sclerosis (n = 36), polymyositis (n = 38), and Sjogren syndrome (n
      = 20). CONCLUSIONS: This microarray system provides results similar to those by
      conventional methods. Assessment of the diagnostic accuracy of the system remains
      to be done.

PMID- 14670826
TI  - Rates of positive cardiac troponin I and creatine kinase MB mass among patients
      hospitalized for suspected acute coronary syndromes.
AB  - BACKGROUND: Cardiac troponin I (cTnI) is a more specific and sensitive biomarker
      than creatine kinase MB (CKMB) for detection of myocardial damage. We report the
      prevalence of positive cTnI and CKMB mass among patients hospitalized with
      suspected acute coronary syndrome (ACS) and the potential impact of use of
      different reference cutoffs, particularly those proposed by European Society of
      Cardiology/American College of Cardiology (ESC/ACC) consensus guidelines, on
      rates of diagnosis of acute myocardial infarction (AMI). METHODS: We analyzed
      1719 consecutive patients with suspected ACS admitted to an urban acute care
      hospital over a 6-month period. Patients (> or = 18 years of age) had at least
      two separate sets of plasma biomarkers (cTnI and CKMB) measured more than 12-24 h
      after admission to determine the potential rates of AMI based on different
      biomarker cutoff concentrations. RESULTS: The prevalence of cTnI-positive cases
      ranged from 10.6%, based on a cutoff of twice the ROC curve (cTnI < or =1.2
      microg/L), to 25.0%, using the ESC/ACC-recommended 99th percentile cutoff (cTnI
      <0.1 microg/L). The prevalence of CKMB-positive cases ranged from 10.4%, with the
      cutoff of twice the ROC curve (CKMB < or =10.0 microg/L) to 21.7%, with the 99th
      percentile cutoff (CKMB <3.9 microg/L). Use of the 10% CV cutoff (cTnI < or =0.3
      microg/L and CKMB <3.9 microg/L) instead of the ROC cutoff produced a 26%
      increase in all cTnI-positive cases. Use of the 99th percentile reference cutoff
      instead of the ROC curve-derived cutoff produced an 85% increase in all cTnI
      positive cases. A substantial proportion of the increase in total cTnI-positive
      cases was derived from cTnI-positive/CKMB-negative cases: 71 (4.1%), 73 (4.2%),
      98 (5.7%), and 209 (12.2%) of cTnI-positive cases were CKMB-negative, as
      determined by the twice the ROC, ROC, 10% CV, and 99th percentile reference
      cutoffs, respectively. At the 99th percentile cutoffs, 8.8% of cases were CKMB
      positive/cTnI-negative. CONCLUSIONS: Use of lower reference cutoffs for plasma
      biomarkers, as recommended by ESC/ACC guidelines, markedly increases the rates of
      cTnI-positive cases overall. A substantial proportion of the increase in total
      cTnI-positive cases was derived from the creation of additional cTnI
      positive/CKMB-negative cases. CKMB-positive/cTnI-negative cases are likely false
      positive for myocardial injury.

PMID- 14670827
TI  - Determination of folate vitamers in human serum by stable-isotope-dilution tandem
      mass spectrometry and comparison with radioassay and microbiologic assay.
AB  - BACKGROUND: Current clinical methods for folate give different results and cannot
      measure the various forms of folate. We developed an isotope-dilution tandem mass
      spectrometric method coupled to liquid chromatography (LC/MS/MS) as a candidate
      reference method for 5-methyltetrahydrofolic acid (5MeTHF), 5
      formyltetrahydrofolic acid (5FoTHF), and folic acid (FA) in human serum. METHODS:
      We quantitatively isolated folates from 275 microL of serum with a phenyl solid
      phase extraction cartridge, then detected and quantified them in stabilized serum
      extracts by positive-ion electrospray ionization LC/MS/MS. We used an isocratic
      mobile phase of acetic acid in organic solvent on a C(8) analytical column. (13)C
      labeled folates were used as internal standards. RESULTS: Limits of detection in
      serum were 0.13 (5MeTHF), 0.05 (5FoTHF), and 0.07 (FA) nmol/L. Within- and
      between-run imprecision (CV) was <7% for 5MeTHF and <10% for 5FoTHF at
      concentrations >0.5 nmol/L, and <10% for FA at concentrations >2.0 nmol/L. Total
      folate (TFOL) concentrations determined by competitive protein binding radioassay
      were approximately 9% lower than results obtained with LC/MS/MS. The
      microbiologic assay gave approximately 15% higher TFOL results with FA calibrator
      and no difference with 5MeTHF calibrator. The mean (SD) [range] TFOL in 42 sera
      was 35.5 (17.8) [6.5-75.6] nmol/L. Thirty-two samples with TFOL <50 nmol/L had,
      on average, 93.3% 5MeTHF, 2.3% FA, and 4.4% 5FoTHF. Ten samples with TFOL >50
      nmol/L had, on average, 81.7% 5MeTHF, 15.7% FA, and 2.5% 5FoTHF. CONCLUSIONS:
      This stable-isotope-dilution LC/MS/MS method can quantify 5MeTHF, 5FoTHF, and FA
      in serum. Currently used clinical assays agree with this candidate reference
      method.

PMID- 14670828
TI  - All strain, no gain: stretch keeps proliferation at bay via the NF-kappaB
      response gene iex-1.

PMID- 14670829
TI  - Hormonal regulation of normal vascular tone in males.

PMID- 14670830
TI  - Noninvasive imaging of myocardial viability: current techniques and future
      developments.
AB  - Complete knowledge of myocardial structure, metabolism, and function is crucial
      to understanding the response of the heart to injury such as ischemia.
      Increasingly, this type of knowledge is required at multiple levels, from that of
      the isolated myocyte to the functioning organism, to provide basic scientists and
      clinical investigators a common framework for translation of findings and
      information feedback. This article focuses on the utilization of imaging methods
      to assess myocardial viability in vivo. It discusses the advantages and pitfalls
      of different imaging techniques, with particular emphasis on available data in
      humans and large animal models. Because of their novelty and potential for
      accurate phenotyping of human pathophysiology, magnetic resonance modalities will
      be highlighted.

PMID- 14670831
TI  - Glycation, inflammation, and RAGE: a scaffold for the macrovascular complications
      of diabetes and beyond.
AB  - The cardiovascular complications of diabetes represent the leading cause of
      morbidity and mortality in affected subjects. The impact of hyperglycemia may be
      both direct and indirect: indirect consequences of elevated blood glucose lead to
      generation of advanced glycation endproducts, the products of nonenzymatic
      glycation/oxidation of proteins/lipids that accumulate in the vessel wall, and
      are signal transduction ligands for Receptor for AGE (RAGE). Although enhanced in
      diabetes, AGE accumulation also occurs in euglycemia and aging, albeit to lower
      degrees, driven by oxidant stress and inflammation. In hyperglycemia, production
      of 3-deoxyglucosone, at least in part via the polyol pathway, provides an
      amplification loop to sustain AGE generation, oxidant stress, and vascular
      activation. Furthermore, recruitment of inflammatory cells bearing
      S100/calgranulins, also ligands for RAGE, augments vascular dysfunction. We
      hypothesize that activation of RAGE is a final common pathway that transduces
      signals from these diverse biochemical and molecular species, leading to
      cardiovascular perturbation. Ultimately, these pathways synergize to construct a
      scaffold on which the complications of diabetes in the vasculature and heart may
      be built. We propose that antagonism of RAGE will provide a unique means to
      dismantle this scaffold and, thereby, suppress initiation/progression of vascular
      disease and cardiac dysfunction that accompany diabetes and aging.

PMID- 14670832
TI  - Modulation of thin filament activation by breakdown or isoform switching of thin
      filament proteins: physiological and pathological implications.
AB  - In the heart, the contractile apparatus is adapted to the specific demands of the
      organ for continuous rhythmic contraction. The specialized contractile properties
      of heart muscle are attributable to the expression of cardiac-specific isoforms
      of contractile proteins. This review describes the isoforms of the thin filament
      proteins actin and tropomyosin and the three troponin subunits found in human
      heart muscle, how the isoform profiles of these proteins change during
      development and disease, and the possible functional consequences of these
      changes. During development of the heart, there is a distinctive switch of
      isoform expression at or shortly after birth; however, during adult life, thin
      filament protein isoform composition seems to be stable despite protein turnover
      rates of 3 to 10 days. The pattern of isoforms of actin, tropomyosin, troponin I,
      troponin C, and troponin T is not affected by aging or heart disease (ischemia
      and dilated cardiomyopathy). The evidence for proteolysis of thin filament
      proteins in situ during ischemia and stunning is evaluated, and it is concluded
      that C-terminal cleavage of troponin I is a feature of irreversibly injured
      myocardium but may not play a role in reversible stunning.

PMID- 14670833
TI  - Ras, Akt, and mechanotransduction in the cardiac myocyte.
AB  - The Ras subfamily of 21-kDa ("small") guanine nucleotide binding proteins [which
      includes Ha-Ras, Ki(A)-Ras, Ki(B)-Ras, and N-Ras] is universally important in
      regulating intracellular signaling events in mammalian cells and controls their
      growth, proliferation, senescence, differentiation, and survival. These Ras
      isoforms act as membrane-associated biological switches that transduce signals
      from transmembrane receptors, thus potentially activating a variety of downstream
      signaling proteins. These include ultimately two Ser/Thr protein kinase families,
      the extracellular signal-regulated kinases 1/2 (ERK1/2) and Akt (or protein
      kinase B). Activation of ERK1/2 has been associated with cardiac myocyte
      hypertrophy (ie, increased cell size and myofibrillogenesis, with concurrent
      transcriptional changes to a fetal pattern of gene expression), whereas
      activation of Akt is associated with the increased protein accretion in
      hypertrophy. Both ERK1/2 and Akt may promote myocyte survival. In the intact
      heart in vivo and in primary cultures of cardiac myocytes, mechanical strain
      induces hypertrophy, a process known as mechanotransduction, which may involve
      Ras, ERK1/2, and Akt. In this study, general and cardiospecific aspects of the
      regulation of Ras and Akt will be described. The various mechanisms through which
      mechanical strain might initiate Ras- or Akt-dependent signaling will be
      discussed. The overall conclusion is that although an involvement of Ras and Akt
      in mechanotransduction is likely, more work (particularly focusing on
      mechanoreception) needs to be undertaken before it is unequivocally established.

PMID- 14670836
TI  - Big mitogen-activated protein kinase (BMK1)/ERK5 protects endothelial cells from
      apoptosis.
AB  - Blood flow that is steady and laminar is known to be atheroprotective. One likely
      mechanism is enhanced endothelial cell (EC) survival. Because the mitogen
      activated protein kinases (MAPKs) are known regulators of cell survival, we
      investigated the role of Big MAPK-1 (BMK1 or ERK5), which is potently stimulated
      by fluid shear stress. To activate BMK1, we overexpressed constitutively active
      (CA)-MEK5 in bovine lung microvascular ECs (BLMECs). Cell apoptosis was induced
      by growth factor deprivation (0% serum for 24 hours). Analysis of cell viability
      with MTT assay showed that activation of BMK1 by CA-MEK5 significantly improved
      cell viability from 48% to 87% and decreased apoptotic cells from 49% to 10%.
      Growth factor deprivation induced caspase-3 activity 5.2-fold, which was
      inhibited (approximately 60%) by CA-MEK5 overexpression. In contrast, inhibiting
      BMK1 activity by overexpressing dominant-negative BMK1 (DN-BMK1) stimulated
      apoptosis in BLMECs. Steady laminar fluid shear stress inhibited BLMEC apoptosis,
      and this protective effect was also reduced significantly by overexpressing DN
      BMK1. Analysis of antiapoptotic mechanisms showed that both shear stress and CA
      MEK5 stimulated phosphorylation of Bad on Ser112 and Ser136, whereas DN-BMK1
      inhibited phosphorylation. Phosphorylation of Bad induced by BMK1 activation was
      independent of Akt, PKA, or p90RSK kinase activity. These results suggest that
      BMK1 activation by steady laminar flow is atheroprotective by inhibiting EC
      apoptosis via phosphorylation of Bad.

PMID- 14670837
TI  - Early growth response-1 promotes atherogenesis: mice deficient in early growth
      response-1 and apolipoprotein E display decreased atherosclerosis and vascular
      inflammation.
AB  - Early growth response-1 (Egr-1) regulates expression of proinflammatory and
      procoagulant genes in acute cell stress. Experimental evidence suggested that Egr
      1 transcripts were upregulated in human atherosclerotic plaques versus adjacent
      unaffected tissue. To test the impact of Egr-1 in chronic vascular stress, we
      examined its role in a murine model of atherosclerosis. Real-time PCR analysis of
      aortae retrieved from apoE-/- mice demonstrated increased Egr-1 transcripts in an
      age-dependent manner, compared with aortae retrieved from C57BL/6 control
      animals. Therefore, homozygous Egr-1-/- mice were bred into the apoE-/-
      background. Homozygous double-knockout mice (Egr-1-/-/apoE-/-) in the C57BL/6
      background were maintained on normal chow diet. At age 14 and 24 weeks,
      atherosclerotic lesion area and complexity at the aortic root were strikingly
      decreased in mice deficient in both Egr-1 and apoE compared with mice deficient
      in apoE alone. In parallel, transcripts for genes regulating the
      inflammatory/prothrombotic response were diminished in Egr-1-/-/apoE-/- aortae
      versus apoE-/-. In vitro, oxidized low-density lipoprotein (OxLDL), a key factor
      inciting atherogenic mechanisms in the vasculature, upregulated Egr-1 expression
      in monocytes via the MEK-ERK1/2 pathway. We conclude that Egr-1 broadly regulates
      expression of molecules critically linked to atherogenesis and lesion
      progression.

PMID- 14670838
TI  - Thrombin- and factor Xa-induced DNA synthesis is mediated by transactivation of
      fibroblast growth factor receptor-1 in human vascular smooth muscle cells.
AB  - Thrombin and factor Xa (FXa) are agonists for G protein-coupled receptors (GPRCs)
      and may contribute to vascular lesion formation by stimulating proliferation of
      vascular smooth muscle cells (SMCs). Mitogenic signaling of GPCRs requires
      transactivation of receptor tyrosine kinases (RTKs). In rat SMCs, thrombin
      transactivates the epidermal growth factor receptor (EGFR) via a pathway that
      involves heparin-binding EGF-like growth factor (HB-EGF) as ligand for EGFR. The
      purpose of this study was to investigate in human SMCs the role of receptor
      transactivation in the mitogenic response to thrombin and FXa. Thrombin (10
      nmol/L) and FXa (100 nmol/L) cause a 3.3- and 2.6-fold increase in DNA synthesis,
      respectively. In human SMCs, neither thrombin nor FXa causes EGFR
      phosphorylation, and blockade of EGFR kinase does not inhibit DNA synthesis.
      However, DNA synthesis and phosphorylation of fibroblast growth factor receptor-1
      (FGFR-1) induced by thrombin or FXa are inhibited by antibodies neutralizing
      basic fibroblast growth factor (bFGF) or by heparin. Hirudin inhibits thrombin-,
      but not FXa-induced mitogenesis, indicating that FXa acts independently of
      thrombin. We further demonstrate by ELISA that upon thrombin and FXa stimulation,
      bFGF is released and binds to the extracellular matrix. Our data suggest that in
      human vascular SMCs, both thrombin and FXa rapidly release bFGF into the
      pericellular matrix. This is followed by transactivation of the FGFR-1 and
      increased proliferation. Heparin may inhibit the mitogenic effects of thrombin
      and FXa in human SMCs by preventing bFGF binding to FGFR-1.

PMID- 14670839
TI  - Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced
      fatal pulmonary hypertension in rats.
AB  - Primary pulmonary hypertension is a fatal disease characterized by endothelial
      dysfunction, hypercontraction and proliferation of vascular smooth muscle cells
      (VSMCs), and migration of inflammatory cells, for which no satisfactory treatment
      has yet been developed. We have recently demonstrated that intracellular
      signaling pathway mediated by Rho-kinase, an effector of the small GTPase Rho, is
      involved in the pathogenesis of arteriosclerosis. In the present study, we
      examined whether the Rho-kinase-mediated pathway is also involved in the
      pathogenesis of fatal pulmonary hypertension in rats. Animals received a
      subcutaneous injection of monocrotaline, which resulted in the development of
      severe pulmonary hypertension, right ventricular hypertrophy, and pulmonary
      vascular lesions in 3 weeks associated with subsequent high mortality rate. The
      long-term blockade of Rho-kinase with fasudil, which is metabolized to a specific
      Rho-kinase inhibitor hydroxyfasudil after oral administration, markedly improved
      survival when started concomitantly with monocrotaline and even when started
      after development of pulmonary hypertension. The fasudil treatment improved
      pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular
      lesions with suppression of VSMC proliferation and macrophage infiltration,
      enhanced VSMC apoptosis, and amelioration of endothelial dysfunction and VSMC
      hypercontraction. These results indicate that Rho-kinase-mediated pathway is
      substantially involved in the pathogenesis of pulmonary hypertension, suggesting
      that the molecule could be a novel therapeutic target for the fatal disorder.

PMID- 14670840
TI  - Specific induction of tie1 promoter by disturbed flow in atherosclerosis-prone
      vascular niches and flow-obstructing pathologies.
AB  - Nonlaminar flow is a major predisposing factor to atherosclerosis. Yet little is
      known regarding hemodynamic gene regulation in disease-prone areas of the
      vascular tree in vivo. We have determined spatial patterns of expression of
      endothelial cell receptors in the arterial tree and of reporter gene constructs
      in transgenic animals. In this study we show that the endothelial cell-specific
      receptor Tie1 is induced by disturbed flow in atherogenic vascular niches.
      Specifically, tie1 expression in the adult is upregulated in vascular
      bifurcations and branching points along the arterial tree. It is often confined
      to a single ring of endothelial cells functioning as sphincters and hence
      experiencing the steepest gradient in shear stress. In aortic valves, tie1 is
      asymmetrically induced only in endothelial cells encountering changes in flow
      direction. Disturbance of laminar flow by a surgical interposition of a vein into
      an artery led to induction of tie1, specifically in the region where the
      differently sized vessels adjoin. In pathological settings, tie1 expression is
      specifically induced in areas of disturbed flow because of the emergence of
      aneurysms and, importantly, in endothelial cells precisely overlying
      atherosclerotic plaques. Hemodynamic features of atherosclerotic lesion-prone
      regions, recreated in vitro with the aid of a flow chamber with a built-in step,
      corroborated an upregulated tie1 promoter activity only in cells residing where
      flow separation and recirculation take place. These defined promoter elements
      might be harnessed for targeting gene expression to atherosclerotic lesions.

PMID- 14670841
TI  - Prevention and reversal of premature endothelial cell senescence and vasculopathy
      in obesity-induced diabetes by ebselen.
AB  - Although the accelerated atherosclerosis and premature aging of the
      cardiovascular system in patients with metabolic syndrome have been appreciated,
      the mechanisms of their development and potential therapeutic interventions
      remain unresolved. Our previous studies implicated advanced glycosylation end
      products in development of premature senescence preventable with a peroxynitrite
      scavenger, ebselen. Therefore, the effect of ebselen on endothelial senescence
      and vasculopathy in a model of metabolic syndrome--Zucker diabetic rats (ZDF)-
      was investigated. Ebselen decreased the abundance of 3-nitrotyrosine-modified
      proteins in ZDF rats. A 6-fold increase in the number of senescent endothelial
      cells in 22-week-old ZDF was prevented by ebselen. Development of vasculopathy,
      as collectively judged by the acetylcholine-induced vasorelaxation, NO
      production, angiogenic competence, and number of circulating microparticles, was
      almost completely prevented when ebselen was administered from 8 to 22 weeks and
      partially reversed when the treatment interval was 13 to 22 weeks. In conclusion,
      premature senescence of endothelial cells is progressively rampant in ZDF rats
      and is associated with the signs of severe vasculopathy. In addition, prevention
      of premature senescence of vascular endothelium through controlled decrease in
      nitrotyrosine formation was chronologically associated with the amelioration of
      vasculopathy, lending support to the idea of the pathogenetic role of premature
      senescence of endothelial cells in diabetic macrovasculopathy.

PMID- 14670842
TI  - Interleukin-1beta, transforming growth factor-beta1, and bradykinin attenuate
      cyclic AMP production by human pulmonary artery smooth muscle cells in response
      to prostacyclin analogues and prostaglandin E2 by cyclooxygenase-2 induction and
      downregulation of adenylyl cyclase isoforms 1, 2, and 4.
AB  - Increased levels of inflammatory cytokines contribute to the pathophysiology of
      pulmonary hypertension. Prostacyclin (PGI2) analogues, which relax pulmonary
      vessels mainly through cAMP elevation, have a major therapeutic role. In this
      study, we show that prolonged incubation with bradykinin (BK), interleukin-1beta
      (IL-1beta), and transforming growth factor-beta1 (TGF-beta1) markedly impairs
      cAMP accumulation in human pulmonary artery smooth muscle cells in response to
      short-term incubation with prostaglandin E2 (PGE2) and the PGI2 analogues
      iloprost and carbaprostacyclin. A similar reduction in cAMP accumulation in
      response to a direct adenylyl cyclase activator, forskolin, suggested that the
      effect was attributable to downregulation of adenylyl cyclase. Reverse
      transcriptase-polymerase chain reaction studies showed downregulation of adenylyl
      cyclase isoforms 1, 2, and 4. The effect of IL-1beta, BK, and TGF-beta1 on cAMP
      levels was abrogated by the selective COX-2 inhibitor NS398. Furthermore, it was
      mimicked by prolonged incubation with the COX-2 product PGE2 and PGI2 analogues
      or the COX substrate arachidonic acid, suggesting that it was mediated by
      endogenous prostanoids produced by COX-2. Consistent with this, IL-1beta, BK, and
      TGF-beta1 all induced COX-2 and PGE2 release. These results show that BK, IL
      1beta, and TGF-beta1 downregulate adenylyl cyclase in human pulmonary artery
      smooth muscle cells via COX-2 induction and prostanoid release. This suggests a
      novel mechanism whereby mediators and cytokines produced in pulmonary
      hypertension may impair the therapeutic effects of prostacyclin analogues such as
      iloprost and carbaprostacyclin.

PMID- 14670843
TI  - Matrix metalloproteinase-9 is required for adequate angiogenic revascularization
      of ischemic tissues: potential role in capillary branching.
AB  - Angiogenesis, an essential component of a variety of physiological and
      pathological processes, offers attractive opportunities for therapeutic
      regulation. We hypothesized that matrix metalloproteinase-9 genetic deficiency
      (MMP-9-/-) will impair angiogenesis triggered by tissue ischemia, induced
      experimentally by femoral artery ligation in mice. To investigate the role of MMP
      9, we performed a series of biochemical and histological analyses, including
      zymography, simultaneous detection of perfused capillaries, MMP-9 promoter
      activity, MMP-9 protein, and macrophages in MMP-9-/- and wild-type (WT) mice. We
      found that ischemia resulted in doubling of capillary density in WT and no change
      in the MMP-9-/- ischemic tissues, which translated into increased (39%) perfusion
      capacity only in the WT at 14 days after ligation. We also confirmed that
      capillaries in the MMP-9-/- presented significantly (P<0.05) less points of
      capillary intersections, interpreted by us as decreased branching. The combined
      conclusions from simultaneous localizations of MMP-9 expression, capillaries, and
      macrophages suggested that macrophage MMP-9 participates in capillary branching.
      Transplantation of WT bone marrow into the MMP-9-/-, restored capillary
      branching, further supporting the contribution of bone marrow-derived macrophages
      in supplying the necessary MMP-9. Our study indicates that angiogenesis triggered
      by tissue ischemia requires MMP-9, which may be involved in capillary branching,
      a potential novel role for this MMP that could be exploited to control
      angiogenesis.

PMID- 14670844
TI  - Nonlinear changes of transmembrane potential during electrical shocks: role of
      membrane electroporation.
AB  - Defibrillation shocks induce nonlinear changes of transmembrane potential
      (DeltaVm) that determine the outcome of defibrillation. As shown earlier, strong
      shocks applied during action potential plateau cause nonmonotonic negative
      DeltaVm, where an initial hyperpolarization is followed by Vm shift to a more
      positive level. The biphasic negative DeltaVm can be attributable to (1) an
      inward ionic current or (2) membrane electroporation. These hypotheses were
      tested in cell cultures by measuring the effects of ionic channel blockers on
      DeltaVm and measuring uptake of membrane-impermeable dye. Experiments were
      performed in cell strands (width approximately 0.8 mm) produced using a technique
      of patterned cell growth. Uniform-field shocks were applied during the action
      potential plateau, and DeltaVm was measured by optical mapping. Shock-induced
      negative DeltaVm exhibited a biphasic shape starting at a shock strength of
      approximately 15 V/cm when estimated peak DeltaV-m was approximately -180 mV;
      positive DeltaVm remained monophasic. Application of a series of shocks with a
      strength of 23+/-1 V/cm resulted in uptake of membrane-impermeable dye propidium
      iodide. Dye uptake was restricted to the anodal side of strands with the largest
      negative DeltaVm, indicating the occurrence of membrane electroporation at these
      locations. The occurrence of biphasic negative DeltaVm was also paralleled with
      after-shock elevation of diastolic Vm. Inhibition of I(f) and I(K1) currents that
      are active at large negative potentials by CsCl and BaCl2, respectively, did not
      affect DeltaVm, indicating that these currents were not responsible for biphasic
      DeltaVm. These results provide evidence that the biphasic shape of DeltaVm at
      sites of shock-induced hyperpolarization is caused by membrane electroporation.

PMID- 14670846
TI  - Cerebral microvascular responses to hypercholesterolemia: roles of NADPH oxidase
      and P-selectin.
AB  - Although hypercholesterolemia is widely accepted as a major risk factor for
      coronary artery and peripheral vascular diseases, its role in the pathogenesis of
      stroke is controversial. The objectives of this study were to determine how
      hypercholesterolemia affects the cerebral microcirculation under resting
      conditions and after ischemia-reperfusion (I/R). Platelet- and leukocyte
      endothelial cell interactions and oxidant production (using the oxidant-sensitive
      fluorochrome dihydrorhodamine-123) were monitored by intravital videomicroscopy
      in the cerebral microvasculature of mice placed on either a normal (ND) or
      cholesterol-enriched diet (HCD). Platelets labeled with carboxyfluorescein
      diacetate succinimidyl ester (CFDASE) and leukocytes labeled with rhodamine 6G
      were seen to roll and firmly adhere, with a corresponding increase in oxidant
      production, in venules of mice on HCD, but not ND. Immunoneutralization of P
      selectin attenuated the platelet- and leukocyte-endothelial cell interactions and
      the enhanced oxidant production associated with HCD. A GPIIb/IIIa blocking
      antibody did not alter the blood cell-vessel wall interactions to HCD. Mice
      deficient in the NADPH oxidase subunit gp91(phox) exhibited significantly blunted
      platelet and leukocyte recruitment responses to HCD. Focal I/R also elicited
      inflammatory and prothrombogenic responses in cerebral venules and these were
      exaggerated in mice on HCD. These results implicate an oxidant-dependent, P
      selectin-mediated mechanism in the blood cell-vessel wall interactions induced by
      hypercholesterolemia in the brain and demonstrate that the deleterious effects of
      I/R on the brain are exacerbated by this cardiovascular risk factor.

PMID- 14670845
TI  - Estrogen elicits cytochrome P450--mediated flow-induced dilation of arterioles in
      NO deficiency: role of PI3K-Akt phosphorylation in genomic regulation.
AB  - This study investigated the mechanisms responsible for the estrogen-dependent,
      cytochrome P450 (CYP)-mediated dilator responses to shear stress in arterioles of
      NO-deficient female rats and mice. Flow-induced dilation (FID) was assessed in
      isolated arterioles from N(G)-nitro-L-arginine methyl ester (L-NAME)-treated male
      and ovariectomized female rats before and after overnight incubation with 17beta
      estradiol (17beta-E2, 10(-9) mol/L). In control conditions, prostaglandins (PGs)
      mediated FID, because indomethacin (INDO) abolished the responses. After
      incubation of the vessels with 17beta-E2, the basal tone of arterioles was
      significantly reduced and FID was augmented. INDO did not affect the dilation of
      the vessels incubated with 17beta-E2. Dilations of these vessels, however, were
      eliminated by PPOH and miconazole, inhibitors of CYP/epoxygenase. Simultaneous
      incubation of the vessels with 17beta-E2 plus ICI, 182,780, an estrogen receptor
      antagonist, or wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K)
      phosphorylation or the transcriptional inhibitor DRB, prevented the reduced
      arteriolar tone and the enhanced CYP-mediated FID caused by incubation of vessels
      with 17beta-E2. Western blot analysis indicated a significantly increased phospho
      Akt level in arterioles incubated with 17beta-E2 compared with those without
      17beta-E2. The enhanced phospho-Akt in response to 17beta-E2 was localized, by
      immunohistochemistry, to arteriolar endothelial cells. Moreover, GC-MS analysis
      indicated a significantly increased production of epoxyeicosatrienoic acids,
      vasodilator metabolites of CYP/epoxygenase, in arterioles incubated with 17beta
      E2, a response that was prevented by ICI 182780 and wortmannin, respectively.
      Thus, estrogen, via a receptor-dependent, PI3K/Akt-mediated pathway,
      transcriptionally upregulates CYP activity, leading to an enhanced arteriolar
      response to shear stress.

PMID- 14670847
TI  - Smooth muscle--specific expression of CYP4A1 induces endothelial sprouting in
      renal arterial microvessels.
AB  - Cytochrome P450 (CYP) 4A1 has been characterized as the most efficient
      arachidonic acid omega-hydroxylase catalyzing the formation of 20
      hydroxyeicosatetraenoic acid (20-HETE), a potent constrictor of the renal and
      cerebral microcirculation and a mitogen for smooth muscle cells. We constructed
      adenoviruses expressing the CYP4A1 cDNA or LacZ under the control of the smooth
      muscle cell-specific promoter SM22alpha (Ad-SM22-4A1 and Ad-SM22-nLacZ,
      respectively). Beta-galactosidase expression was detected in Ad-SM22-nLacZ
      transduced vascular smooth muscle A7r5 and PAC1 cells, but not in Ad-SM22-nLacZ
      transduced 3T3 fibroblasts or vascular endothelial cells. Likewise, CYP4A1 mRNA
      and protein were detected in Ad-SM22-4A1-transduced A7r5 and PAC1 cells. Ad-SM22
      4A1-transduced A7r5 cells metabolized lauric acid to 12-hydroxy-lauric acid at a
      rate 5 times greater than that of cells transduced with Ad-SM22-nLacZ (4.79+/
      1.77 versus 0.97+/-0.57 nmol 12-hydroxy lauric acid/10(6) cells per h). Smooth
      muscle-specific LacZ expression was also detected in microdissected renal
      interlobar arteries transduced with Ad-SM22-nLacZ. Arteries transduced with Ad
      SM22-4A1 produced higher levels of 20-HETE (4.04+/-0.29 and 13.43+/-2.84 ng/mg
      protein in Ad-SM22-nLacZ-transduced and Ad-SM22-4A1-transduced arteries,
      respectively) and demonstrated a marked angiogenic activity measured as the total
      length of sprouting neovessels (12.63+/-3.66 mm in Ad-SM22-4A1-transduced vessels
      versus 1.79+/-0.89 mm in Ad-SM22-nLacZ-transduced vessels). This angiogenic
      activity represented endothelial cell sprouting and was fully blocked by
      treatment with HET0016, a selective inhibitor of CYP4A-catalyzed reactions. The
      inhibitory effect of HET0016 was reversed by addition of a 20-HETE agonist. We
      conclude that Ad-SM22-4A1 drives a smooth muscle-specific functional expression
      of CYP4A1 and demonstrates increased angiogenesis, presumably via increased
      production of 20-HETE.

PMID- 14670848
TI  - Intracellular localization and functional effects of P21-activated kinase-1
      (Pak1) in cardiac myocytes.
AB  - We investigated intracellular localization and substrate specificity of P21
      activated kinase-1 (Pak1) in rat cardiac myocytes. Pak1 is a serine/threonine
      protein kinase that is activated by Rac1/Cdc42 and important in signaling of
      stress responses. Yet the localization and in vivo function of Pak1 in heart
      cells is poorly understood. Studies reported here indicate that Pak1 physically
      interacts with protein phosphatase 2a and localizes to the Z-disk, cell membrane,
      intercalated disc, and nuclear membrane of adult rat heart myocytes. We compared
      levels of phosphorylation of cardiac troponin I (cTnI) in control myocytes with
      phosphorylation of cTnI and myosin binding protein C (C-protein) in myocytes with
      increased Pak1 activity. The increase in activity was induced by infection of
      myocytes with a recombinant adenovirus (AdPak1) containing cDNA for a
      constitutively active Pak1. Control cells were infected with a virus (AdLacZ)
      containing LacZ. Basal levels of phosphorylation of cTnI and C-protein were
      relatively high in the myocytes infected with AdLacZ. However, phosphorylation of
      cTnI and C-protein in cells expressing constitutively active Pak1 was
      significantly reduced compared with those expressing LacZ. Measurement of Ca2+
      tension relations in single myocytes demonstrated that this reduction in
      phosphorylation of cTnI and C-protein was associated with the predicted increase
      in sensitivity to Ca2+. Our data provide evidence for a novel pathway of
      phosphatase regulation in cardiac myocytes.

PMID- 14670849
TI  - Morphological and functional alterations in ventricular myocytes from male
      transgenic mice with hypertrophic cardiomyopathy.
AB  - Familial hypertrophic cardiomyopathy (FHC) is a human genetic disorder caused by
      mutations in sarcomeric proteins. It is generally characterized by cardiac
      hypertrophy, fibrosis, and myocyte disarray. A transgenic mouse model of FHC with
      mutations in the actin-binding domain of the alpha-myosin heavy chain (MyHC) gene
      displays many phenotypes similar to human FHC. At 4 months, male transgenic (TG)
      mice present with concentric cardiac hypertrophy that progresses to dilation with
      age. Accompanying this latter morphological change is systolic and diastolic
      dysfunction. Left ventricular (LV) myocytes from male TG and wild-type (WT)
      littermates at 5 and 12 months of age were isolated and used for morphological
      and functional studies. Myocytes from 5- and 12-month-old TG animals had shorter
      sarcomere lengths compared with WT. This sarcomere length difference was
      abolished in the presence of 2,3-butanedione monoxime, suggesting that the basal
      level of contractile element activation was increased in TG myocytes. Myocytes
      from 12-month-old TG mice were significantly longer than those from age-matched
      WT controls, and TG myocytes exhibited Z-band disorganization. When cells were
      paced at 0.5 Hz, TG myocyte relengthening and the fall in intracellular [Ca2+]
      were slowed when compared with cells from age-matched WT controls. Moreover, an
      increased amount of beta-myosin heavy chain protein was found in hearts from TG
      compared with WT. Thus, myocytes from the alpha-MyHC TG mouse model display many
      morphological and functional abnormalities that may help explain the LV
      dysfunction seen in this TG mouse model of FHC.

PMID- 14670850
TI  - The health consequences of the first Gulf war.

PMID- 14670852
TI  - Treatment options for trigeminal neuralgia.

PMID- 14670851
TI  - Evening primrose oil for atopic dermatitis.

PMID- 14670853
TI  - Delayed prescriptions.

PMID- 14670854
TI  - Monitoring the medical education revolution.

PMID- 14670859
TI  - Children have been neglected in flu prevention strategy.

PMID- 14670860
TI  - Huge numbers must change lifestyle to prevent epidemic of diabetes.

PMID- 14670867
TI  - Adverse events in surgery in Scotland show a steady fall.

PMID- 14670868
TI  - Test case may threaten abortion rights.

PMID- 14670872
TI  - Seven international companies join global fund.

PMID- 14670874
TI  - Experts predict big rise in dengue fever in South East Asia.

PMID- 14670875
TI  - A third of UK households have at least one adult in pain.

PMID- 14670876
TI  - Australian government tries to stop independent advice on diabetes drugs.

PMID- 14670877
TI  - Better communication is key to recruiting patients to trials.

PMID- 14670878
TI  - Gulf war illness--better, worse, or just the same? A cohort study.
AB  - OBJECTIVES: Firstly, to describe changes in the health of Gulf war veterans
      studied in a previous occupational cohort study and to compare outcome with
      comparable non-deployed military personnel. Secondly, to determine whether
      differences in prevalence between Gulf veterans and controls at follow up can be
      explained by greater persistence or greater incidence of disorders. DESIGN:
      Occupational cohort study in the form of a postal survey. PARTICIPANTS: Military
      personnel who served in the 1991 Persian Gulf war; personnel who served on
      peacekeeping duties to Bosnia; military personnel who were deployed elsewhere
      ("Era" controls). All participants had responded to a previous survey. SETTING:
      United Kingdom. MAIN OUTCOME MEASURES: Self reported fatigue measured on the
      Chalder fatigue scale; psychological distress measured on the general health
      questionnaire, physical functioning and health perception on the SF-36; and a
      count of physical symptoms. RESULTS: Gulf war veterans experienced a modest
      reduction in prevalence of fatigue (48.8% at stage 1, 43.4% at stage 2) and
      psychological distress (40.0% stage 1, 37.1% stage 2) but a slight worsening of
      physical functioning on the SF-36 (90.3 stage 1, 88.7 stage 2). Compared with the
      other cohorts Gulf veterans continued to experience poorer health on all
      outcomes, although physical functioning also declined in Bosnia veterans. Era
      controls showed both lower incidence of fatigue than Gulf veterans, and both
      comparison groups showed less persistence of fatigue compared with Gulf veterans.
      CONCLUSIONS: Gulf war veterans remain a group with many symptoms of ill health.
      The excess of illness at follow up is explained by both higher incidence and
      greater persistence of symptoms.

PMID- 14670879
TI  - Incidence of cancer among UK Gulf war veterans: cohort study.
AB  - OBJECTIVES: To determine whether incidence rates of cancer are higher in UK
      service personnel who were deployed in the Gulf war than in those not deployed
      and whether any increased risk of cancer is related to self reported exposures to
      potentially hazardous material during the period of deployment. DESIGN: A cohort
      study with follow up from 1 April 1991 (the end of the Gulf war) to 31 July 2002.
      PARTICIPANTS: 51 721 Gulf war veterans and 50 755 service personnel matched for
      age, sex, rank, service, and level of fitness who were not deployed in the Gulf
      (the Era cohort). MAIN OUTCOME MEASURES: Incident cancers, identified on the NHS
      central register. RESULTS: There were 270 incident cancers among the Gulf cohort
      and 269 among the Era cohort (incidence rate ratio 0.99, 95% confidence interval
      0.83 to 1.17). There was no excess in site specific cancers among the Gulf
      cohort. Adjustment for lifestyle factors (smoking and alcohol consumption) did
      not alter these results. In the Gulf cohort, risk of cancer was not related to
      multiple vaccinations or exposure to pesticides or depleted uranium during
      deployment. CONCLUSION: There is no current excess risk of cancer overall nor of
      site specific cancers in Gulf war veterans. Specific exposures during deployment
      have not resulted in a subsequent increased risk of cancer. The long latent
      period for cancer, however, necessitates the continued follow up of these
      cohorts.

PMID- 14670880
TI  - Risk of suicide and related adverse outcomes after exposure to a suicide
      prevention programme in the US Air Force: cohort study.
AB  - OBJECTIVE: To evaluate the impact of the US Air Force suicide prevention
      programme on risk of suicide and other outcomes that share underlying risk
      factors. DESIGN: Cohort study with quasi-experimental design and analysis of
      cohorts before (1990-6) and after (1997-2002) the intervention. PARTICIPANTS:
      5,260,292 US Air Force personnel (around 84% were men). INTERVENTION: A
      multilayered intervention targeted at reducing risk factors and enhancing factors
      considered protective. The intervention consisted of removing the stigma of
      seeking help for a mental health or psychosocial problem, enhancing understanding
      of mental health, and changing policies and social norms. MAIN OUTCOME MEASURES:
      Relative risk reductions (the prevented fraction) for suicide and other outcomes
      hypothesised to be sensitive to broadly based community prevention efforts,
      (family violence, accidental death, homicide). Additional outcomes not
      exclusively associated with suicide were included because of the
      comprehensiveness of the programme. RESULTS: Implementation of the programme was
      associated with a sustained decline in the rate of suicide and other adverse
      outcomes. A 33% relative risk reduction was observed for suicide after the
      intervention; reductions for other outcomes ranged from 18-54%. CONCLUSION: A
      systemic intervention aimed at changing social norms about seeking help and
      incorporating training in suicide prevention has a considerable impact on
      promotion of mental health. The impact on adverse outcomes in addition to suicide
      strengthens the conclusion that the programme was responsible for these
      reductions in risk.

PMID- 14670882
TI  - Security duties in Northern Ireland and the mental health of soldiers:
      prospective study.

PMID- 14670881
TI  - Prophylactic respiratory physiotherapy after cardiac surgery: systematic review.
AB  - OBJECTIVE: To assess whether respiratory physiotherapy prevents pulmonary
      complications after cardiac surgery. DATA SOURCES: Searches through Medline,
      Embase, Cinahl, the Cochrane library, and bibliographies, for randomised trials
      comparing any type of prophylactic respiratory physiotherapy with another type or
      no intervention after cardiac surgery, with a follow up of at least two days, and
      reporting on respiratory outcomes. REVIEW METHODS: Investigators assessed trial
      validity independently. Information on study design, population, interventions,
      and end points was abstracted by one investigator and checked by the others.
      RESULTS: 18 trials (1457 patients) were identified. Most were of low quality.
      They tested physical therapy (13 trials), incentive spirometry (eight),
      continuous positive airway pressure (five), and intermittent positive pressure
      breathing (three). The maximum follow up was six days. Four trials only had a no
      intervention control; none showed any significant benefit of physiotherapy.
      Across all trials and interventions, average values postoperatively were:
      incidence of atelectasis, 15-98%; incidence of pneumonia, 0-20%; partial pressure
      of arterial oxygen per inspired oxygen fraction, 212-329 mm Hg; vital capacity,
      37-72% of preoperative values; and forced expiratory volume in one second, 34
      72%. No intervention showed superiority for any end point. For the most labour
      intensive intervention, continuous positive airway pressure, the average cost of
      labour for each patient day was 27 euro (pound 19; 32 dollars). CONCLUSIONS: The
      usefulness of respiratory physiotherapy for the prevention of pulmonary
      complications after cardiac surgery remains unproved. Large randomised trials are
      needed with no intervention controls, clinically relevant end points, and
      reasonable follow up periods.

PMID- 14670883
TI  - Association of insulin resistance with depression: cross sectional findings from
      the British Women's Heart and Health Study.

PMID- 14670884
TI  - Pulmonary embolism possibly associated with olanzapine treatment.

PMID- 14670885
TI  - Efficacy and tolerability of borage oil in adults and children with atopic
      eczema: randomised, double blind, placebo controlled, parallel group trial.
AB  - OBJECTIVE: To study the efficacy and tolerability of borage oil, which contains a
      high concentration of gamma linolenic acid, in children and adults with atopic
      eczema. DESIGN: Single centre, randomised, double blind, placebo controlled,
      parallel group trial. SETTING: Acute district general hospital in Nuneaton,
      England. PARTICIPANTS: 151 patients, of whom 11 failed to return for assessment,
      leaving an evaluable population of 140 (including 69 children). INTERVENTION:
      Adults received four capsules of borage oil twice daily (920 mg gamma linolenic
      acid), and children received two capsules twice daily, for 12 weeks. MAIN OUTCOME
      MEASURES: Change in total sign score at 12 weeks measured with the six area, six
      sign, atopic dermatitis (SASSAD) score (primary endpoint); symptom scores,
      assessed on visual analogue scales; topical corticosteroid requirement, assessed
      on a five point scale; global assessment of response by participants; adverse
      events and tolerability. RESULTS: The mean SASSAD score fell from 30 to 27 in the
      borage oil group and from 28 to 23 in the placebo group. The difference between
      the mean improvements in the two groups was 1.4 (95% confidence interval -2.2 to
      5.0) points in favour of placebo (P = 0.45). No significant differences occurred
      between treatment groups in the other assessments. Subset analysis of adults and
      children did not indicate any difference in response. The treatments were well
      tolerated. CONCLUSION: Gamma linolenic acid is not beneficial in atopic
      dermatitis.

PMID- 14670886
TI  - Health of young and elderly informal carers: analysis of UK census data.

PMID- 14670887
TI  - Can gynaecology teaching associates provide high quality effective training for
      medical students in the United Kingdom? Comparative study.
AB  - OBJECTIVES: To train laywomen to become professional patients in order to teach
      medical students speculum and bimanual examination, to assess their effectiveness
      in this role, and to incorporate this method of teaching into the undergraduate
      curriculum of a medical school in the United Kingdom. DESIGN: Comparative study.
      SETTING: Guy's, King's, and St Thomas's School of Medicine, London. PARTICIPANTS:
      44 medical students trained by gynaecology teaching associates; 48 control
      students. MAIN OUTCOME MEASURE: Skills in pelvic examination. RESULTS: Six
      laywomen were recruited and all successfully graduated to become gynaecology
      teaching associates. At assessment 1, in the third week of the reproductive and
      sexual health block, the mean score achieved by students trained by gynaecology
      teaching associates was 155, compared with 104 for control group students
      (difference in mean scores 51 (95% confidence interval 41 to 61), P < 0.001).
      Similar results were obtained at assessment 2, at the end of the attachment-the
      mean score for trained students was 148, compared with a mean score of 114 for
      control group students (difference in mean scores 34 (21 to 46), P < 0.001).
      CONCLUSIONS: Laywomen can be trained to teach pelvic examination to medical
      students in the United Kingdom. Students who receive this training have better
      skills than students who receive the traditional training alone.

PMID- 14670889
TI  - Treating nicotine addiction.

PMID- 14670890
TI  - Putting the research into practice.

PMID- 14670891
TI  - Information for patients: getting professional help.

PMID- 14670892
TI  - Rethinking prescribing in the United States.

PMID- 14670893
TI  - Research with unaccompanied children seeking asylum.

PMID- 14670894
TI  - Communicating risk: compulsory measures can work.

PMID- 14670895
TI  - Communicating risk: patients often have complex understanding of risk.

PMID- 14670896
TI  - Communicating risk: journalists take note.

PMID- 14670897
TI  - Communicating risk: we as doctors are not alone.

PMID- 14670898
TI  - Communicating risk: journalists have responsibility to report risks in context.

PMID- 14670899
TI  - Drug sales in four European countries still differ.

PMID- 14670900
TI  - Communicating risk: but does it work, Doctor?

PMID- 14670901
TI  - Communicating risk: doctor's recommendation is decision making in uncertain
      conditions.

PMID- 14670902
TI  - Prognosis for South Asian and white patients with heart failure in the United
      Kingdom: counterintuitive findings on heart failure in South Asians may be
      artefactual.

PMID- 14670903
TI  - Real time assay of Aspergillus should be used in SARS patients receiving
      corticosteroids.

PMID- 14670904
TI  - Adherence to advance directives: GMC's advance directive is commendable.

PMID- 14670905
TI  - Adherence to advance directives: quality of life matters.

PMID- 14670906
TI  - Prognosis for South Asian and white patients with heart failure in the United
      Kingdom: deprivation gradient in mortality should not be dismissed as
      artefactual.

PMID- 14670907
TI  - Adherence to advance directives: maybe doctors do not always know best.

PMID- 14670908
TI  - Radiographic results are still not routinely reported.

PMID- 14670909
TI  - Adherence to advance directives: quality of life may be important in advance
      directives.

PMID- 14670910
TI  - Adherence to advance directives: advance directive needs to include additional
      elements.

PMID- 14670911
TI  - Rehabilitation medicine.

PMID- 14670913
TI  - Improving the mental health of doctors.

PMID- 14670915
TI  - HAMP as a modifier gene that increases the phenotypic expression of the HFE
      pC282Y homozygous genotype.
AB  - Hereditary hemochromatosis is a genetically heterogeneous disease of iron
      metabolism. The most common form of the disorder is an adult-onset form that has
      mainly been associated with the HFE pC282Y/pC282Y genotype. The phenotypic
      expression of this genotype is very heterogeneous and could be modulated by both
      environmental factors and modifier genes. The non-HFE hereditary hemochromatosis
      forms include a juvenile onset form associated with mutations in HAMP. From a
      cohort of 392 C282Y homozygous patients, we found 5 carriers of an additional
      HAMP mutation at the heterozygous state (pR59G, pG71D, or pR56X). We found that
      iron indices of these 5 patients were among the most elevated of the cohort.
      Moreover, we specified that the HAMP mutations were not detected in 300 control
      subjects. These results revealed that mutations in HAMP might increase the
      phenotypic expression of the pC282Y/pC282Y genotype. From a cohort of 31 patients
      with at least one chromosome lacking an HFE mutation, we further identified 4
      males carrying a heterozygous HAMP mutation (pR59G or pG71D). Based on a digenic
      model of inheritance, these data suggest that the association of heterozygous
      mutations in the HFE and HAMP genes could lead, at least in some cases, to an
      adult-onset form of primary iron overload.

PMID- 14670916
TI  - Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid
      dendritic cell precursors from human hematopoietic progenitors.
AB  - Type 1 interferon-producing cells (IPCs), also known as plasmacytoid dendritic
      cell (DC) precursors, represent the key effectors in antiviral innate immunity
      and triggers for adaptive immune responses. IPCs play important roles in the
      pathogenesis of systemic lupus erythematosus (SLE) and in modulating immune
      responses after hematopoietic stem cell transplantation. Understanding IPC
      development from hematopoietic progenitor cells (HPCs) may provide critical
      information in controlling viral infection, autoimmune SLE, and graft-versus-host
      disease. FLT3-ligand (FLT3-L) represents a key IPC differentiation factor from
      HPCs. Although hematopoietic cytokines such as interleukin-3 (IL-3), IL-7, stem
      cell factor (SCF), macrophage-colony-stimulating factor (M-CSF), and granulocyte
      M-CSF (GM-CSF) promote the expansion of CD34+ HPCs in FLT3-L culture, they
      strongly inhibit HPC differentiation into IPCs. Here we show that thrombopoietin
      (TPO) cooperates with FLT3-L, inducing CD34+ HPCs to undergo a 400-fold expansion
      in cell numbers and to generate more than 6 x 10(6) IPCs per 10(6) CD34+ HPCs
      within 30 days in culture. IPCs derived from HPCs in FLT3-L/TPO cultures display
      blood IPC phenotype and have the capacity to produce large amounts of interferon
      alpha (IFN-alpha) and to differentiate into mature DCs. This culture system,
      combined with the use of adult peripheral blood CD34+ HPCs purified from G-CSF
      mobilized donors, permits the generation of more than 10(9) IPCs from a single
      blood donor.

PMID- 14670917
TI  - Rapid generation of combined CMV-specific CD4+ and CD8+ T-cell lines for adoptive
      transfer into recipients of allogeneic stem cell transplants.
AB  - Adoptive transfer of cytomegalovirus (CMV)-specific T cells can restore long
      lasting, virus-specific immunity and clear CMV viremia in recipients of
      allogeneic stem cell transplants if CD4(+) and CD8(+) CMV-specific T cells are
      detected in the recipient after transfer. Current protocols for generating virus
      specific T cells use live virus, require leukapheresis of the donor, and are time
      consuming. To circumvent these limitations, a clinical-scale protocol was
      developed to generate CMV-specific T cells by using autologous cellular and serum
      components derived from a single 500-mL blood draw. CMV-specific T cells were
      stimulated simultaneously with CMV-specific major histocompatibility complex
      class I (MHC I)- restricted peptides and CMV antigen. Activated T cells were
      isolated with the interferon-gamma (IFN-gamma) secretion assay and expanded for
      10 days. In 8 randomly selected, CMV-seropositive donors, 1.34 x 10(8) combined
      CD4(+) and CD8(+) CMV-specific T cells, on average, were generated, as determined
      by antigen-triggered IFN-gamma production. CMV-infected fibroblasts were
      efficiently lysed by the generated T cells, and CMV-specific CD4(+) and CD8(+) T
      cells expanded if they were stimulated with natural processed antigen. On the
      other hand, CD4(+) and CD8(+) T cell-mediated alloreactivity of generated CMV
      specific T-cell lines was reduced compared with that of the starting population.
      In conclusion, the culture system developed allowed the rapid generation of
      allodepleted, highly enriched, combined CD4(+) and CD8(+) CMV-specific T cells
      under conditions mimicking good manufacturing practice.

PMID- 14670919
TI  - Intracellular serpin SERPINB6 (PI6) is abundantly expressed by human mast cells
      and forms complexes with beta-tryptase monomers.
AB  - SERPINB6 (PI6) is a member of the intracellular serine protease inhibitors
      (serpins). Previous studies showed that SERPINB6 is localized mainly in the
      cytoplasm of endothelial cells, some epithelial cells, monocytes, and
      neutrophils. In these cells SERPINB6 is thought to prevent cellular damage by
      scavenging leaking lysosomal proteases. We show here, using novel, well-defined
      monoclonal antibodies, that SERPINB6 is abundantly expressed by mast cells in all
      organs and by the human mast cell line HMC-1. Gel filtration experiments revealed
      that the latter cells contain a high-molecular-weight form of SERPINB6, which
      consists of sodium dodecyl sulfate (SDS)-stable complexes of this inhibitor with
      monomeric beta-tryptase. Expression of SERPINB6 by mast cells was compared with
      those of tryptase and CD117 (c-kit) in biopsies from patients with different
      forms of mast cell disease. In all cases the lesional mast cells expressed
      SERPINB6, and, in diffuse cutaneous mastocytosis and mastocytoma, SERPINB6 was
      expressed by a substantially higher number of mast cells when compared with
      tryptase. In conclusion, SERPINB6 is abundantly expressed by normal mast cells
      and by mast cells in mastocytoma lesions. We suggest that in mast cells, SERPINB6
      serves to regulate the activity of endogenous beta-tryptase in the cytoplasm.

PMID- 14670924
TI  - FLT3 mutations in childhood acute lymphoblastic leukemia.
AB  - Activating mutations of the FLT3 receptor tyrosine kinase are common in acute
      myelogenous leukemia (AML) but are rare in adult acute lymphoblastic leukemia
      (ALL). We have recently shown that FLT3 is highly expressed and often mutated in
      ALLs with rearrangement of the mixed lineage leukemia (MLL) gene on chromosome
      11q23. Because hyperdiploid ALL samples also show high-level expression of FLT3,
      we searched for the presence of FLT3 mutations in leukemic blasts from 71
      patients with ALL. The data show that approximately 25% (6 of 25) of hyperdiploid
      ALL samples possess FLT3 mutations, whereas only 1 of 29 TEL/AML1-rearranged
      samples harbored mutations (P =.04, Fisher exact test). Three mutations are novel
      in-frame deletions within a 7-amino acid region of the receptor juxtamembrane
      domain. Finally, 3 samples from patients whose disease would relapse harbored
      FLT3 mutations. These data suggest that patients with hyperdiploid or relapsed
      ALL might be considered candidates for therapy with newly described small
      molecule FLT3 inhibitors.

PMID- 14670925
TI  - Involvement of Notch-1 signaling in bone marrow stroma-mediated de novo drug
      resistance of myeloma and other malignant lymphoid cell lines.
AB  - The bone marrow (BM) microenvironment plays a critical role in malignant cell
      growth, patient survival, and response to chemotherapy in hematologic
      malignancies. However, mechanisms associated with this environmental influence
      remain unclear. In this study, we investigated the role of Notch family proteins
      in myeloma and other malignant lymphoid cell line growth and response to
      chemotherapeutic drugs. All 8 tested cell lines expressed Notch-3 and Notch-4; 7
      cell lines expressed Notch-1; and 6 expressed Notch-2 proteins. Interaction with
      BM stroma (BMS) activated Notch signaling in tumor cells. However, activation of
      only Notch-1, but not Notch-2, resulted in protection of tumor cells from
      melphalan- and mitoxantrone-induced apoptosis. This protection was associated
      with up-regulation of p21(WAF/Cip) and growth inhibition of cells. Overexpression
      of Notch-1 in Notch-1(-) U266 myeloma cells up-regulated p21 and resulted in
      protection from drug-induced apoptosis. Thus, this is a first report
      demonstrating that Notch-1 signaling may be a primary mechanism mediating the BMS
      influence on hematologic malignant cell growth and survival.

PMID- 14670926
TI  - Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a
      type-1 polarized immune response.
AB  - Derangement of cellular immunity is central in the pathophysiology of adult
      autoimmune/idiopathic thrombocytopenic purpura (ITP). Herein we investigated
      cytokine gene expression in peripheral blood mononuclear cells (PBMCs) of adult
      chronic ITP patients and attempted to correlate cytokine polarization with the
      degree of thrombocytopenia. We used semiquantitative reverse-transcriptase
      polymerase chain reaction (RT-PCR) to measure the expression of type-1
      (interleukin-2 [IL-2], interferon gamma [IFN-gamma]) and type-2 (IL-4, IL-5, IL
      10, IL-3, IL-13) cytokines by PBMCs from 21 patients and 11 controls. Plasma
      transforming growth factor beta1 (TGF-beta1) levels were measured by enzyme
      linked immunoassay (ELISA). T helper 1 (Th1)/Th2 ([IL-2 + IFN-gamma]/[IL-4 + IL
      5]) cytokine mRNA ratios, thought to reflect the Th deviation of the pathogenic
      disease-specific T cells, and type-1/type-2 mRNA ratios, thought to reflect the
      overall immune response polarization, were significantly increased in ITP
      patients. The Th1/Th2 ratio was inversely correlated with platelet counts. TGF
      beta1 levels appeared suppressed in patients with active disease, though not
      significantly. Our findings show a clear type-1 cytokine polarization of the
      autoimmune response in adult ITP that persists irrespective of disease status.

PMID- 14670927
TI  - In vivo neutralization of a C2 domain-specific human anti-Factor VIII inhibitor
      by an anti-idiotypic antibody.
AB  - Factor VIII (FVIII) administration elicits specific inhibitory antibodies (Abs)
      in about 25% of patients with hemophilia A. The majority of such Abs reacts with
      FVIII C2 domain. mAbBO2C11 is a high-affinity human monoclonal antibody (mAb)
      directed toward the C2 domain, which is representative of a major class of human
      FVIII inhibitors. Anti-idiotypic Abs were raised to mAbBO2C11 to establish their
      neutralizing potential toward inhibitors. One mouse anti-idiotypic mAb, mAb14C12,
      specifically prevented mAbBO2C11 binding to FVIII C2 domain and fully neutralized
      mAbBO2C11 functional inhibitory properties. Modeling of the 3-D conformation of
      mAb14C12 VH and alignment with the 3-D structure of the C2 domain showed putative
      31 surface-exposed amino acid residues either identical or homologous to the C2
      domain. These included one C2 phospholipid-binding site, Leu2251-Leu2252, but not
      Met2199-Phe2200. Forty putative contact residues with mAbBO2C11 were identified.
      mAb14C12 dose-dependently neutralized mAbBO2C11 inhibitory activity in mice with
      hemophilia A reconstituted with human recombinant FVIII (rFVIII), allowing full
      expression of FVIII activity. It also neutralized in an immunoprecipitation assay
      approximately 50% of polyclonal anti-C2 Abs obtained from 3 of 6 unrelated
      patients. mAb14C12 is the first example of an anti-idiotypic Ab that fully
      restores FVIII activity in vivo in the presence of an anti-C2 inhibitor. The
      present results establish the in vitro and in vivo proof of concept for idiotype
      mediated neutralization of a major class of FVIII inhibitors.

PMID- 14670928
TI  - Association of biallelic BRCA2/FANCD1 mutations with spontaneous chromosomal
      instability and solid tumors of childhood.
AB  - The clinical, cytogenetic, and molecular findings of 2 Fanconi anemia (FA)
      subtype D1 kindreds, initially identified through a young child with a solid
      tumor (medullobastoma, Wilms tumor), are described. Each kindred subsequently had
      a second affected child; one developed Wilms tumor followed by a medulloblastoma,
      and the other developed T-lineage acute lymphoblastic leukemia. Cytogenetic
      studies revealed an unusually high spontaneous chromosome aberration rate,
      contrasting with other FA subtypes. Molecular analysis revealed biallelic
      BRCA2/FANCD1 mutations. The patients did not exhibit bone marrow failure. Our
      studies suggest that the D1 subtype represents a severe end of the cytogenetic
      spectrum within FA, consistent with a critical downstream role of BRCA2 in the FA
      pathway. Furthermore, this FA subgroup may be preferentially associated with an
      increased predisposition to solid tumors in early childhood. Recognition of this
      constellation of findings has significant implications for medical management and
      genetic counseling of FA families.

PMID- 14670929
TI  - The prognostic impact of autologous stem cell transplantation in patients with
      chronic lymphocytic leukemia: a risk-matched analysis based on the VH gene
      mutational status.
AB  - To assess the therapeutic value of sequential high-dose therapy (SHDT) including
      autologous stem cell transplantation in chronic lymphocytic leukemia (CLL) we
      performed a risk-matched comparison between 66 patients who had undergone a
      uniform SHDT regimen and a database of 291 patients treated conventionally.
      Matching variables were age, Binet stage, IgVH (variable region of the
      immunoglobulin heavy chain) gene mutational status, and lymphocyte count. Forty
      four pairs fully matched for all 4 variables were identified. Patient groups were
      well balanced for additional risk factors including adverse genomic abnormalities
      and CD38 expression. With an overall median follow-up time of 70 and 86 months,
      respectively, survival was significantly longer for the SHDT patients than for
      the conventionally treated patients when calculated from diagnosis (hazard ratio
      [HR] 0.39; P=.03 [log rank]) or from study entry (HR 0.32; P=.006). The benefit
      for the SHDT group remained significant when the analyses were restricted to
      those 58 patients who had an unmutated VH status. Cox regression analysis
      confirmed SHDT as independent favorable prognostic factor for survival from
      diagnosis (HR 0.38, P=.04) as well as from study entry (HR 0.38, P=.03). These
      data suggest a survival benefit for patients with poor-risk CLL receiving SHDT
      during the course of their disease.

PMID- 14670931
TI  - High glucose-induced upregulation of osteopontin is mediated via Rho/Rho kinase
      pathway in cultured rat aortic smooth muscle cells.
AB  - OBJECTIVE: Osteopontin is upregulated in the diabetic vascular wall and in
      vascular smooth muscle cells cultured under high glucose concentration. In the
      present study, we analyzed the mechanism of high glucose-induced upregulation of
      osteopontin in cultured rat aortic smooth muscle cells. METHODS AND RESULTS: We
      found that an inhibitor of Rho-associated protein kinase, Y-27632, suppressed
      osteopontin mRNA expression under high glucose concentration. Transfection of
      cells with a constitutive active Rho mutant, pSRalpha-myc-RhoDA, enhanced
      osteopontin mRNA expression. Furthermore, incubation of cells under high glucose
      concentration activated Rho, indicating that Rho/Rho kinase pathway mediates high
      glucose-stimulated osteopontin expression. Treatment of cells with an inhibitor
      of protein kinase C, GF109203X, and azaserine, an inhibitor of the hexosamine
      pathway, suppressed high glucose-induced Rho activation. Glucosamine treatment
      was shown to activate Rho. Treatment of cells with an inhibitor of MEK1, PD98059,
      suppressed osteopontin mRNA expression under high glucose concentration.
      Incubation of cells under high glucose concentration activated ERK. Finally,
      transfection of cells with pSRalpha-myc-RhoDA also activated ERK. CONCLUSIONS: In
      conclusion, our present findings support a notion that Rho/Rho kinase pathway
      functions downstream of protein kinase C and the hexosamine pathways and upstream
      of ERK in mediating high-glucose-induced upregulation of osteopontin expression.

PMID- 14670932
TI  - Inhibition of intimal thickening in the rat carotid artery injury model by a
      nontoxic Ras inhibitor.
AB  - BACKGROUND: Neointimal formation with and without previous vascular injury is
      common after balloon dilation and in transplant arteriosclerosis. It involves
      proliferation and migration of medial smooth muscle cells and inflammation,
      processes that are regulated by Ras proteins and their down-stream effectors.
      Farnesylthiosalicylate (FTS) is a Ras inhibitor that interferes with Ras membrane
      anchorage and affects Ras proteins in their active state. In the present study,
      we tested the hypothesis that systemic administration of FTS will suppress
      intimal thickening in the rat carotid injury model. METHODS AND RESULTS: The
      effects of FTS on rat vascular smooth muscle cells (VSMC) and splenocytes
      proliferation were evaluated in vitro. The in vivo effects of FTS on the
      neointima of balloon-injured male Wistar rats, treated daily for 2 weeks with FTS
      (5 mg/kg weight, intraperitoneally) were evaluated by determination of Ras, Ras
      GTP, and active ERK levels (3 days after injury), and by quantitative
      determination of the extent of intimal thickening and immunohistochemistry for
      Ras, iNOS, NFkB, and Ki-67 (2 weeks after injury). FTS inhibited VSMC and
      splenocyte proliferation as well as interferon-gamma secretion by splenocytes in
      a dose-dependent manner. Compared with controls, FTS treatment resulted in a
      strong decrease in Ras-GTP and active ERK, and it significantly reduced intimal
      thickening after the injury. Ras expression appeared predominantly at areas of
      neointima regardless of the treatment group. NFkB and iNOS-positive cell numbers
      were reduced in sections of FTS treated rats. CONCLUSIONS: FTS appears to act as
      a potent inhibitor of intimal thickening in a model of experimental arterial
      injury.

PMID- 14670933
TI  - Hyperlipidemia promotes osteoclastic potential of bone marrow cells ex vivo.
AB  - OBJECTIVE: Osteoporosis is associated epidemiologically with atherosclerosis and
      hyperlipidemia. We previously found that atherogenic lipids regulate bone
      formation. To determine whether hyperlipidemia also affects bone resorption, we
      compared osteoclastogenesis in marrow preosteoclasts derived from hyperlipidemic
      versus control mice. METHODS: Nonadherent marrow cells from low-density
      lipoprotein receptor-/- (LDLR-/-)and C57BL/6J mice were cultured with M-CSF and
      ligand for receptor activator of nuclear factor-kappaB (RANKL). Functional
      osteoclastic activity, measured as number of resorption pits, was significantly
      greater in 12-month-old LDLR-/-. Similar results were obtained in 5- and 10-month
      old LDLR-/- versus C57BL/6J mice on a high-fat diet. Osteoclastic
      differentiation, indicated by tartrate resistant acid phosphatase (TRAP)
      activity, was significantly greater in the 12-month-old LDLR-/-, and there was a
      trend toward increased TRAP activity in LDLR-/- on a high-fat diet, at ages 5 and
      10 months. Osteoclastic parameters correlated with total serum lipoproteins with
      a possible threshold effect. Osteoporotic human cortical bone stained positive
      for lipids in the perivascular space of Haversian canals by oil red O. The
      presence of lipid hydroperoxides was detected in bone marrow from hyperlipidemic
      mice. CONCLUSIONS: Hyperlipidemia may contribute to osteoporosis via increased
      osteoclastic bone resorption.

PMID- 14670934
TI  - Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth muscle
      cells.
AB  - OBJECTIVE: Reactive oxygen species (ROS) that act as signaling molecules in
      vascular smooth muscle cells (VSMC) and contribute to growth, hypertrophy, and
      migration in atherogenesis are produced by multi-subunit NAD(P)H oxidases. Nox1
      and Nox4, two homologues to the phagocytic NAD(P)H subunit gp91phox, both
      generate ROS in VSMC but differ in their response to growth factors. We
      hypothesize that the opposing functions of Nox1 and Nox4 are reflected in their
      differential subcellular locations. METHODS AND RESULTS: We used
      immunofluorescence to visualize the NAD(P)H subunits Nox1, Nox4, and p22phox in
      cultured rat and human VSMC. Optical sectioning using confocal microscopy showed
      that Nox1 is co-localized with caveolin in punctate patches on the surface and
      along the cellular margins, whereas Nox4 is co-localized with vinculin in focal
      adhesions. These immunocytochemical distributions are supported by membrane
      fractionation experiments. Interestingly, p22phox, a membrane subunit that
      interacts with the Nox proteins, is found in surface labeling and in focal
      adhesions in patterns similar to Nox1 and Nox4, respectively. CONCLUSIONS: The
      differential roles of Nox1 and Nox4 in VSMC may be correlated with their
      differential compartmentalization in specific signaling domains in the membrane
      and focal adhesions.

PMID- 14670935
TI  - Apolipoprotein C-I induces apoptosis in human aortic smooth muscle cells via
      recruiting neutral sphingomyelinase.
AB  - OBJECTIVE: Apolipoprotein C-I (apoC-I) influences lipoprotein metabolism, but
      little is known about its cellular effects in aortic smooth muscle cells (ASMC).
      METHODS AND RESULTS: In cultured human ASMC, apoC-I and immunoaffinity purified
      apoC-I-enriched high-density lipoproteins (HDL) markedly induced apoptosis (5- to
      25-fold), compared with control cells, apoC-I-poor HDL, and apolipoprotein C-III
      (apoC-III) as determined by 4', 6-diamidino-2-phenylindole dihydrochloride
      staining and DNA ladder assay. Preincubation of cells with GW4869, an inhibitor
      of neutral sphingomyelinase (N-SMase), blocked apoC-I-induced apoptosis, an
      effect that was bypassed by C-2 ceramide. The activity of N-SMase was increased 2
      to 3-fold in ASMC by apoC-I, apoC-I-enriched HDL, and tumor necrosis factor
      alpha (TNF-alpha) (positive control) after 10 minutes and then decreased over 60
      minutes, which is a kinetic pattern not seen with controls, apoC-III, and apoC-I
      poor HDL. ApoC-I and apoC-I-enriched HDL stimulated the generation of ceramide,
      the release of cytochrome c from mitochondria, and activation of caspase-3
      greater than that found in controls, apoC-III, and apoC-I-poor HDL. GW4869
      inhibited apoC-I-induced production of ceramide and cytochrome c release.
      CONCLUSIONS: ApoC-I and apoC-I-enriched HDL activate the N-SMase-ceramide
      signaling pathway, leading to apoptosis in human ASMC, which is an effect that
      may promote plaque rupture in vivo.

PMID- 14670946
TI  - Androgen receptor acetylation site mutations cause trafficking defects,
      misfolding, and aggregation similar to expanded glutamine tracts.
AB  - Kennedy's disease is a degenerative disorder of motor neurons caused by the
      expansion of a glutamine tract near the amino terminus of the androgen receptor
      (AR). Ligand binding to the receptor is associated with several post
      translational modifications, but it is poorly understood whether these affect the
      toxicity of the mutant protein. Our studies now demonstrate that mutation of
      lysine residues in wild-type AR that are normally acetylated in a ligand
      dependent manner mimics the effects of the expanded glutamine tract on receptor
      trafficking, misfolding, and aggregation. Mutation of lysines 630 or 632 and 633
      to alanine markedly delays ligand-dependent nuclear translocation. The
      K632A/K633A mutant also undergoes ligand-dependent misfolding and aggregation
      similar to the expanded glutamine tract AR. This acetylation site mutant exhibits
      ligand-dependent 1C2 immunoreactivity, forms aggregates that co-localize with
      Hsp40, Hsp70, and the ubiquitin-protein isopeptide ligase (E3) ubiquitin ligase
      carboxyl terminus of Hsc70-interacting protein (CHIP), and inhibits proteasome
      function. Ligand-dependent nuclear translocation of the wild-type receptor and
      misfolding and aggregation of the K632A/K633A mutant are blocked by radicicol, an
      Hsp90 inhibitor. These data identify a novel role for the acetylation site as a
      regulator of androgen receptor subcellular distribution and folding and indicate
      that ligand-dependent aggregation is dependent upon intact Hsp90 function.

PMID- 14670947
TI  - Inhibition of the yeast cytochrome bc1 complex by ilicicolin H, a novel inhibitor
      that acts at the Qn site of the bc1 complex.
AB  - Ilicicolin H is an antibiotic isolated from the "imperfect" fungus
      Cylindrocladium iliciola strain MFC-870. Ilicicolin inhibits mitochondrial
      respiration by inhibiting the cytochrome bc(1) complex. In order to identify the
      site of ilicicolin action within the bc(1) complex we have characterized the
      effects of ilicicolin on the cytochrome bc(1) complex of Saccharomyces
      cerevisiae. Ilicicolin inhibits ubiquinol-cytochrome c reductase activity of the
      yeast bc(1) complex with an IC(50) of 3-5 nM, while 200-250 nM ilicicolin was
      required to obtain comparable inhibition of the bovine bc(1) complex. Ilicicolin
      blocks oxidation-reduction of cytochrome b through center N of the bc(1) complex
      and promotes oxidant-induced reduction of cytochrome b but has no effect on
      oxidation of ubiquinol through center P. These results indicate that ilicicolin
      binds to the Qn site of the bc(1) complex. Ilicicolin induces a blue shift in the
      absorption spectrum of ferro-cytochrome b, and titration of the spectral shift
      indicates binding of one inhibitor molecule per Qn site. The effects of
      ilicicolin on electron transfer reactions in the bc(1) complex are similar to
      those of antimycin, another inhibitor that binds to the Qn site of the bc(1)
      complex. However, because the two inhibitors have different effects on the
      absorption spectrum of cytochrome b, they differ in their mode of binding to the
      Qn site.

PMID- 14670948
TI  - Disulfide cross-linking analysis shows that transmembrane segments 5 and 8 of
      human P-glycoprotein are close together on the cytoplasmic side of the membrane.
AB  - Human P-glycoprotein (P-gp) transports a wide variety of structurally diverse
      compounds out of the cell. Knowledge about the packing of the transmembrane (TM)
      segments is essential for understanding the mechanism of drug recognition and
      transport. We used cysteine-scanning mutagenesis and disulfide cross-linking
      analysis to determine which TM segment in the COOH half of P-gp was close to TMs
      5 and 6 since these segments in the NH(2) half are important for drug binding. An
      active Cys-less P-gp mutant cDNA was used to generate 240 double cysteine mutants
      that contained 1 cysteine in TMs 5 or 6 and another in TMs 7 or 8. The mutants
      were subjected to oxidative cross-linking analysis. No disulfide cross-linking
      was observed in the 140 TM6/TM7 or TM6/TM8 mutants. By contrast, cross-linking
      was detected in several P-gp TM5/TM8 mutants. At 4 degrees C, when thermal motion
      is low, P-gp mutants N296C(TM5)/G774C(TM8), I299C(TM5)/F770C(TM8),
      I299C(TM5)/G774C(TM8), and G300C(TM5)/F770C(TM8) showed extensive cross-linking
      with oxidant. These mutants retained drug-stimulated ATPase activity, but their
      activities were inhibited after treatment with oxidant. Similarly, disulfide
      cross-linking was inhibited by vanadate trapping of nucleotide. These results
      indicate that significant conformational changes must occur between TMs 5 and 8
      during ATP hydrolysis. We revised the rotational symmetry model for TM packing
      based on our results and by comparison to the crystal structure of MsbA (Chang,
      G. (2003) J. Mol. Biol. 330, 419-430) such that TM5 is adjacent to TM8, TM2 is
      adjacent to TM11, and TMs 1 and 7 are next to TMs 6 and 12, respectively.

PMID- 14670949
TI  - Lipopolysaccharide induces CYP2E1 in astrocytes through MAP kinase kinase-3 and
      C/EBPbeta and -delta.
AB  - Cytochrome P450 2E1 (CYP2E1) is highly inducible in a subset of astrocytes in
      vivo following ischemic or mechanical injury and in vitro by lipopolysaccharide
      (LPS) or interleukin-1beta. We have studied the mechanism of induction, and found
      that transcriptional activation of CYP2E1 occurred within 3 h, and CYP2E1
      dependent catalytic activity was induced more than 4-fold within 5 h. The
      induction was sensitive to several tyrosine kinase inhibitors, and was further
      modulated by inhibitors of p38 MAP kinase. MAP kinase kinase-3 (MKK3) was
      phosphorylated in response to LPS, and expression of constitutively active MKK3,
      but not the MAP kinase kinases MEKK1 or MKK1, activated CYP2E1. Transcriptional
      activation was mediated through a C/EBPbeta and -delta binding element situated
      at -486/-474, and appeared to involve activation of prebound factors as well as
      recruitment of newly synthesized C/EBPbeta and -delta. It is thus suggested that
      LPS induces MKK3 activation in astrocytes, which in turn stimulates a C/EBPbeta
      and -delta binding element to mediate transcriptional activation of CYP2E1.

PMID- 14670950
TI  - Glycosylation broadens the substrate profile of membrane type 1 matrix
      metalloproteinase.
AB  - Membrane type 1 matrix metalloproteinase (MT1-MMP) is a collagenolytic enzyme
      that has been implicated in normal development and in pathological processes such
      as cancer metastasis. The activity of MT1-MMP is regulated extensively at the
      post-translational level, and the current data support the hypothesis that MT1
      MMP activity is modulated by glycosylation. Enzymatic deglycosylation, site
      directed mutagenesis, and lectin precipitation assays were used to demonstrate
      that MT1-MMP contains O-linked complex carbohydrates on the Thr(291), Thr(299),
      Thr(300), and/or Ser(301) residues in the proline-rich linker region. MT1-MMP
      glycoforms were detected in human cancer cell lines, suggesting that MT1-MMP
      activity may be regulated by differential glycosylation in vivo. Although the
      autolytic processing and interstitial collagenase activity of MT1-MMP were not
      impaired in glycosylation-deficient mutants, cell surface MT1-MMP-catalyzed
      activation of pro-matrix metalloproteinase-2 (proMMP-2) required proper
      glycosylation of MT1-MMP. The inability of carbohydrate-free MT1-MMP to activate
      proMMP-2 was not a result of defective MT1-MMP zymogen activation, aberrant
      protein stability, or inability of the mature enzyme to oligomerize. Rather, our
      data support a mechanism whereby glycosylation affects the recruitment of tissue
      inhibitor of metalloproteinases-2 (TIMP-2) to the cell surface, resulting in
      defective formation of the MT1-MMP/TIMP-2/proMMP-2 trimeric activation complex.
      These data provide evidence for an additional mechanism for post-translational
      control of MT1-MMP activity and suggest that glycosylation of MT1-MMP may
      regulate its substrate targeting.

PMID- 14670951
TI  - Structural and biochemical analysis of Cellvibrio japonicus xylanase 10C: how
      variation in substrate-binding cleft influences the catalytic profile of family
      GH-10 xylanases.
AB  - Microbial degradation of the plant cell wall is the primary mechanism by which
      carbon is utilized in the biosphere. The hydrolysis of xylan, by endo-beta-1,4
      xylanases (xylanases), is one of the key reactions in this process. Although
      amino acid sequence variations are evident in the substrate binding cleft of
      "family GH10" xylanases (see afmb.cnrs-mrs.fr/CAZY/), their biochemical
      significance is unclear. The Cellvibrio japonicus GH10 xylanase CjXyn10C is a bi
      modular enzyme comprising a GH10 catalytic module and a family 15 carbohydrate
      binding module. The three-dimensional structure at 1.85 A, presented here, shows
      that the sequence joining the two modules is disordered, confirming that linker
      sequences in modular glycoside hydrolases are highly flexible. CjXyn10C
      hydrolyzes xylan at a rate similar to other previously described GH10 enzymes but
      displays very low activity against xylooligosaccharides. The poor activity on
      short substrates reflects weak binding at the -2 subsite of the enzyme.
      Comparison of CjXyn10C with other family GH10 enzymes reveals "polymorphisms" in
      the substrate binding cleft including a glutamate/glycine substitution at the -2
      subsite and a tyrosine insertion in the -2/-3 glycone region of the substrate
      binding cleft, both of which contribute to the unusual properties of the enzyme.
      The CjXyn10C-substrate complex shows that Tyr-340 stacks against the xylose
      residue located at the -3 subsite, and the properties of Y340A support the view
      that this tyrosine plays a pivotal role in substrate binding at this location.
      The generic importance of using CjXyn10C as a template in predicting the
      biochemical properties of GH10 xylanases is discussed.

PMID- 14670952
TI  - Relationship between growth rate and ATP concentration in Escherichia coli: a
      bioassay for available cellular ATP.
AB  - Previous studies showed that adenosine triphosphate (ATP) concentrations in
      Escherichia coli changed during certain growth transitions and directly
      controlled the rate of rRNA transcription initiation at those times. The
      relationship between ATP concentration and rRNA transcription during steady-state
      growth is less clear, however. This is because two commonly employed methods for
      measuring ATP concentrations in bacteria, both of which rely on physical
      extraction followed by chromatographic separation of small molecules, resulted in
      dramatically different conclusions about whether ATP concentration changed with
      steady-state growth rate. Extraction with formic acid indicated that ATP
      concentration did not change with growth rate, whereas formaldehyde treatment
      followed by extraction with alkali indicated that ATP concentration increased
      proportionally to the growth rate. To resolve this discrepancy, we developed a
      bioassay for ATP based on the expression of a variant of the firefly luciferase
      enzyme in vivo and measurement of luminescence in cells growing in different
      conditions. We found that the available ATP concentration did not vary with
      growth rate, either in wild-type cells or in cells lacking guanosine 5'
      diphosphate, 3'-diphosphate, providing insight into the regulation of rRNA
      transcription. More broadly, the luciferase bioassay described here provides a
      general method for evaluating the ATP concentration available for biochemical
      processes in E. coli and potentially in other organisms.

PMID- 14670953
TI  - Binding of free immunoglobulin light chains to VpreB3 inhibits their maturation
      and secretion in chicken B cells.
AB  - The VpreB3 gene product was first characterized as an immunoglobulin (Ig) mu
      heavy chain-binding protein in mouse precursor B (pre-B) cells. Although its
      function is unknown, it has been proposed to participate in the assembly and
      transport of the pre-B cell receptor. We have identified a VpreB3 orthologous
      gene in chicken that is located close to the immunoglobulin light chain (LC) gene
      cluster and specifically expressed in the bursa of Fabricius. By overexpressing
      VpreB3 in the DT40 IgM(+) immature chicken B cell line, we have characterized
      VpreB3 as an endoplasmic reticulum-resident glycoprotein that binds
      preferentially to free IgLC. However, binding to IgHC is observed in IgLC
      deficient DT40 cells. Interaction of VpreB3 with free IgLC is partly covalent and
      induces retention of free IgLC in the endoplasmic reticulum, preventing their
      secretion without affecting IgM surface expression. Our results demonstrate that
      this evolutionarily conserved molecule may play a role in the regulation of the
      maturation and secretion of free IgLC in B cells. We discuss possible
      implications in the regulation of the immune response.

PMID- 14670954
TI  - The single dynamin-like protein of Trypanosoma brucei regulates mitochondrial
      division and is not required for endocytosis.
AB  - Members of the evolutionarily conserved dynamin-related GTPase family mediate
      numerous cellular membrane remodeling events. Dynamin family functions include
      the scission of clathrin-coated pits from the plasma membrane, mitochondrial
      fission, and chloroplast division. Here we report that the divergent eukaryote
      Trypanosoma brucei possesses a single dynamin family gene, which we have
      designated TbDLP. Furthermore, a single dynamin family gene is also found in the
      Leishmania major and Trypanosoma vivax genomes, indicating that this is a
      conserved feature among the kinetoplastida. TbDLP is most homologous to the
      DMN/DRP family of dynamin-like proteins. Indirect immunofluorescence microscopy
      reveals that TbDLP is distributed in punctate structures within the cell that
      partially co-localize with the mitochondrion when labeled with MitoTracker. To
      define TbDLP function, we have used RNA interference to silence the TbDLP gene.
      Reduction of TbDLP protein levels causes a profound alteration in mitochondrial
      morphology without affecting the structure of other membrane-bound compartments,
      including the endocytic and exocytic apparatus. The mitochondrial profiles
      present in wild type trypanosomes fuse and collapse in the mutant cells, and by
      electron microscopy the mitochondria are found to contain an accumulation of
      constriction sites. These findings demonstrate TbDLP functions in division of the
      mitochondrial membrane. Most significantly, as TbDLP is the sole member of the
      dynamin family in this organism, scission of clathrin-coated pits involved in
      protein trafficking through the highly active endocytic system in trypanosomes
      must function in the absence of dynamin. The evolutionary implications of these
      findings are discussed.

PMID- 14670955
TI  - Src homology 3 binding sites in the P2Y2 nucleotide receptor interact with Src
      and regulate activities of Src, proline-rich tyrosine kinase 2, and growth factor
      receptors.
AB  - Many G protein-coupled receptors activate growth factor receptors, although the
      mechanisms controlling this transactivation are unclear. We have identified two
      proline-rich, SH3 binding sites (PXXP) in the carboxyl-terminal tail of the human
      P2Y(2) nucleotide receptor that directly associate with the tyrosine kinase Src
      in protein binding assays. Furthermore, Src co-precipitated with the P2Y(2)
      receptor in 1321N1 astrocytoma cells stimulated with the P2Y(2) receptor agonist
      UTP. A mutant P2Y(2) receptor lacking the PXXP motifs was found to stimulate
      calcium mobilization and serine/threonine phosphorylation of the Erk1/2 mitogen
      activated protein kinases, like the wild-type receptor, but was defective in its
      ability to stimulate tyrosine phosphorylation of Src and Src-dependent tyrosine
      phosphorylation of the proline-rich tyrosine kinase 2, epidermal growth factor
      receptor (EGFR), and platelet-derived growth factor receptor. Dual
      immunofluorescence labeling of the P2Y(2) receptor and the EGFR indicated that
      UTP caused an increase in the co-localization of these receptors in the plasma
      membrane that was prevented by the Src inhibitor PP2. Together, these data
      suggest that agonist-induced binding of Src to the SH3 binding sites in the
      P2Y(2) receptor facilitates Src activation, which recruits the EGFR into a
      protein complex with the P2Y(2) receptor and allows Src to efficiently
      phosphorylate the EGFR.

PMID- 14670956
TI  - Involvement of the ERK signaling cascade in protein kinase C-mediated cell cycle
      arrest in intestinal epithelial cells.
AB  - We have reported previously that protein kinase C (PKC) signaling can mediate a
      program of cell cycle withdrawal in IEC-18 nontransformed intestinal crypt cells,
      involving rapid disappearance of cyclin D1, increased expression of Cip/Kip
      cyclin-dependent kinase inhibitors, and activation of the growth suppressor
      function of pocket proteins. In the current study, we present evidence to support
      a requisite role for PKC alpha in mediating these effects. Furthermore, analysis
      of the signaling events linking PKC/PKC alpha activation to changes in the cell
      cycle regulatory machinery implicate the Ras/Raf/MEK/ERK cascade. PKC/PKC alpha
      activity promoted GTP loading of Ras, activation of Raf-1, and
      phosphorylation/activation of ERK. ERK activation was found to be required for
      critical downstream effects of PKC/PKC alpha activation, including cyclin D1 down
      regulation, p21(Waf1/Cip1) induction, and cell cycle arrest. PKC-induced ERK
      activation was strong and sustained relative to that produced by proliferative
      signals, and the growth inhibitory effects of PKC agonists were dominant over
      proliferative events when these opposing stimuli were administered
      simultaneously. PKC signaling promoted cytoplasmic and nuclear accumulation of
      ERK activity, whereas growth factor-induced phospho-ERK was localized only in the
      cytoplasm. Comparison of the effects of PKC agonists that differ in their ability
      to sustain PKC alpha activation and growth arrest in IEC-18 cells, together with
      the use of selective kinase inhibitors, indicated that the length of PKC-mediated
      cell cycle exit is dictated by the magnitude/duration of input signal (i.e. PKC
      alpha activity) and of activation of the ERK cascade. The extent/duration of
      phospho-ERK nuclear localization may also be important determinants of the
      duration of PKC agonist-induced growth arrest in this system. Taken together, the
      data point to PKC alpha and the Ras/Raf/MEK/ERK cascade as key regulators of cell
      cycle withdrawal in intestinal epithelial cells.

PMID- 14670957
TI  - Crystal structures of decorated xylooligosaccharides bound to a family 10
      xylanase from Streptomyces olivaceoviridis E-86.
AB  - The family 10 xylanase from Streptomyces olivaceoviridis E-86 (SoXyn10A) consists
      of a GH10 catalytic domain, which is joined by a Gly/Pro-rich linker to a family
      13 carbohydrate-binding module (CBM13) that interacts with xylan. To understand
      how GH10 xylanases and CBM13 recognize decorated xylans, the crystal structure of
      SoXyn10A was determined in complex with alpha-l-arabinofuranosyl- and 4-O-methyl
      alpha-d-glucuronosyl-xylooligosaccharides. The bound sugars were observed in the
      subsites of the catalytic cleft and also in subdomains alpha and gamma of CBM13.
      The data reveal that the binding mode of the oligosaccharides in the active site
      of the catalytic domain is entirely consistent with the substrate specificity
      and, in conjunction with the accompanying paper, demonstrate that the
      accommodation of the side chains in decorated xylans is conserved in GH10
      xylanases of SoXyn10A against arabinoglucuronoxylan. CBM13 was shown to bind
      xylose or xylooligosaccharides reversibly by using nonsymmetric sugars as the
      ligands. The independent multiple sites in CBM13 may increase the probability of
      substrate binding.

PMID- 14670958
TI  - X-ray crystallographic and site-directed mutagenesis analysis of the mechanism of
      Schiff-base formation in phosphonoacetaldehyde hydrolase catalysis.
AB  - Phosphonoacetaldehyde hydrolase (phosphonatase) catalyzes the hydrolytic P-C bond
      cleavage of phosphonoacetaldehyde (Pald) to form orthophosphate and acetaldehyde.
      The reaction proceeds via a Schiff-base intermediate formed between Lys-53 and
      the Pald carbonyl. The x-ray crystal structures of the wild-type phosphonatase
      complexed with Mg(II) alone or with Mg(II) plus vinylsulfonate (a
      phosphonoethylenamine analog) were determined to 2.8 and 2.4 A, respectively.
      These structures were used to determine the identity and positions of active site
      residues surrounding the Lys-53 ammonium group and the Pald carbonyl. These
      include Cys-22, His-56, Tyr-128, and Met-49. Site-directed mutagenesis was then
      employed to determine whether or not these groups participate in catalysis. Based
      on rate contributions, Tyr-128 and Cys-22 were eliminated as potential catalytic
      groups. The Lys-53 epsilon-amino group, positioned for reaction with the Pald
      carbonyl, forms a hydrogen bond with water 120. Water 120 is also within hydrogen
      bond distance of an imidazole nitrogen of His-56 and the sulfur atom of Met-49.
      Kinetic constants for mutants indicated that His-56 (1000-fold reduction in
      k(cat)/K(m) upon Ala substitution) and Met-49 (17,000-fold reduction in
      k(cat)/K(m) upon Leu substitution) function in catalysis of Schiff-base
      formation. Based on these results, it is proposed that a network of hydrogen
      bonds among Lys-53, water 120, His-56, and Met-49 facilitate proton transfer from
      Lys-53 to the carbinolamine intermediate. Comparison of the vinylsulfonate
      complex versus unliganded structures indicated that association of the cap and
      core domains is essential for the positioning of the Lys-53 for attack at the
      Pald carbonyl and that substrate binding at the core domain stabilizes cap domain
      binding.

PMID- 14670959
TI  - The toxoplasma proteins MIC2 and M2AP form a hexameric complex necessary for
      intracellular survival.
AB  - Toxoplasma gondii parasites gain entry into host cells through a process that
      depends on apically stored adhesins that are strategically released during
      invasion. One of these adhesins, microneme protein 2 (MIC2), is a type one
      transmembrane protein that binds to an accessory protein known as MIC2-associated
      protein (M2AP). Together the MIC2 x M2AP complex participates in host cell
      attachment and invasion. The short cytoplasmic C-domain of MIC2 is implicated in
      protein trafficking and mediating an association with the parasite cytoskeleton.
      To define the role of the cytoplasmic domain of MIC2, proteins lacking the C
      domain were expressed in transgenic T. gondii. Surprisingly, protein trafficking
      and secretion were not affected. We hypothesized that mutant mic2 lacking the C
      domain might be escorted to the micronemes by association with endogenous wild
      type MIC2 possessing functional transmembrane and cytoplasmic domains. To
      investigate this interaction, native blue gels and gel filtration were employed
      to identify a stable macromolecular MIC2 x M2AP complex of approximately 450 kDa.
      Our findings reveal that MIC2 and M2AP proteins form stable hexamers consisting
      of three alphabeta dimers. Resolution of this complex has implications for how
      MIC2 x M2AP associates with host cell receptors and the cytoskeleton to
      facilitate parasite motility and invasion.

PMID- 14670960
TI  - Bcr-Abl regulates protein kinase Ciota (PKCiota) transcription via an Elk1 site
      in the PKCiota promoter.
AB  - The protein kinase C (PKC) family of serine/threonine kinases plays an important
      role in numerous cancer signaling pathways, including those downstream of the bcr
      abl oncogene. We demonstrated previously that atypical PKCiota is required for
      Bcr-Abl-mediated resistance of human K562 chronic myelogenous leukemia (CML)
      cells to Taxol-induced apoptosis. Here, we report that the pattern of PKC isozyme
      expression characteristic of CML cells is regulated by Bcr-Abl. When Bcr-Abl was
      expressed in Bcr-Abl-negative HL-60 promyelocytic leukemia cells, expression of
      the PKCbetaI, PKCbetaII, and PKCiota genes was induced, whereas expression of the
      PKCdelta gene was reduced to levels similar to those found in CML cells. Given
      the importance of PKCiota in Bcr-Abl-mediated transformation, we characterized
      the mechanism by which Bcr-Abl regulates PKCiota expression. A 1200-bp PKCiota
      promoter construct isolated from genomic DNA was highly active in Bcr-Abl
      positive K562 cells and was activated when Bcr-Abl-negative cells were
      transfected with Bcr-Abl. Bcr-Abl-mediated induction of the PKCiota promoter was
      dependent upon MEK1/2 activity, but not phosphatidylinositol 3-kinase or p38 MAPK
      activity. Mutational analysis of the PKCiota promoter revealed a region between
      97 and 114 bp upstream of the transcriptional start site that is responsible for
      Bcr-Abl-mediated regulation. Mutation of a consensus Elk1-binding site within
      this region abolished Bcr-Abl-mediated regulation. We conclude that Bcr-Abl
      regulates PKCiota expression through the MEK-dependent activation of an Elk1
      element within the proximal PKCiota promoter. Our results indicate that Bcr-Abl
      mediated transformation involves transcriptional activation of the PKCiota gene,
      which in turn is required for Bcr-Abl-mediated chemoresistance.

PMID- 14670961
TI  - RICK activates a NF-kappaB-dependent anti-human cytomegalovirus response.
AB  - The adapter kinase receptor interacting protein-like interacting caspase-like
      apoptosis regulatory protein kinase (RICK, also called RIP2 and CARDIAK) was
      found to be elevated at both the protein and RNA levels during human
      cytomegalovirus (HCMV) replication, suggesting either that the virus may require
      RICK for replication or that RICK is part of an unsuccessful host attempt to
      inhibit HCMV replication. It is demonstrated here that forced expression of RICK
      in either a kinase active or inactive form activates nuclear factor (NF)-kappaB
      by means of its intermediate domain and potently blocks HCMV replication in human
      fibroblasts. Importantly, NF-kappaB activation, which exerted a modestly positive
      effect on the early phase of infection, clearly had a strongly negative impact
      during later viral steps. A stable inhibitor of NF-kappaB (IkappaB) reverses the
      RICK inhibitory effect, and activation of NF-kappaB by IkappaB kinase beta
      expression is inhibitory to HCMV, demonstrating that NF-kappaB activation is part
      of a potent anti-HCMV response. Supernatant transfer experiments identified
      interferon-beta as a downstream component of the RICK inhibitory pathway. RICK
      expression was found to synergize with HCMV infection in the induction of
      interferon-beta expression. This study identifies an endogenous RICK-activated,
      NF-kappaB- and interferon-beta-dependent antiviral pathway that is either
      inhibited or faulty under normal HCMV replication conditions; efforts to bolster
      this pathway may lead to novel anti-viral approaches.

PMID- 14670962
TI  - A novel transmembrane protein recruits numb to the plasma membrane during
      asymmetric cell division.
AB  - Numb, an evolutionarily conserved cell fate-determining factor, plays a pivotal
      role in the development of Drosophila and vertebrate nervous systems. Despite
      lacking a transmembrane segment, Numb is associated with the cell membrane during
      the asymmetric cell division of Drosophila neural precursor cells and is
      selectively partitioned to one of the two progeny cells from a binary cell
      division. Numb contains an N-terminal phosphotyrosine-binding (PTB) domain that
      is essential for both the asymmetric localization and the fate specification
      function of Numb. We report here the isolation and characterization of a novel
      PTB domain-binding protein, NIP (Numb-interacting protein). NIP is a multipass
      transmembrane protein that contains two PTB domain-binding, NXXF motifs required
      for the interaction with Numb. In dividing Drosophila neuroblasts, NIP is
      colocalized to the cell membrane with Numb in a basal cortical crescent.
      Expression of NIP in Cos-7 cells recruited Numb from the cytosol to the plasma
      membrane. This recruitment of Numb to membrane by NIP was dependent on the
      presence of at least one NXXF site. In Drosophila Schneider 2 cells, NIP and Numb
      were colocalized at the plasma membrane. Inhibition of NIP expression by RNA
      interference released Numb to the cytosol. These results suggest that a direct
      protein-protein interaction between NIP and Numb is necessary and sufficient for
      the recruitment of Numb to the plasma membrane. Recruitment of Numb to a basal
      cortical crescent in a dividing neuroblast is essential for Numb to function as
      an intrinsic cell fate determinant.

PMID- 14670963
TI  - Annexin II is required for apical transport in polarized epithelial cells.
AB  - The sorting of apical proteins comprises an initial recognition step in the trans
      Golgi network and a final partitioning of the apical pool of proteins into at
      least two different types of vesicular carriers. One criteria of these carriers
      is the association or non-association of the protein content with lipid rafts. We
      have previously characterized a population containing the raft-associated sucrase
      isomaltase-carrying vesicles (SAVs) and another one, the non-raft-associated
      lactase-phlorizin hydrolase-carrrying vesicles (LAVs) that are targeted
      separately to the apical membrane. Here, we demonstrate biochemically and by
      employing confocal laser microscopy that the annexin II-S100A10 complex is a
      component of SAVs and is absent from LAVs. The unequivocal role of annexin II in
      the apical targeting of SI is clearly demonstrated when down-regulation of this
      protein by annexin II-specific small interfering RNA drastically decreases the
      apical delivery of SI in the epithelial cell line Madin-Darby canine kidney. The
      annexin II-S100A10 complex plays therefore a crucial role in routing SAVs to the
      apical membrane of epithelial cells.

PMID- 14670964
TI  - Oxidative cross-linking of tryptophan to glycine restrains matrix
      metalloproteinase activity: specific structural motifs control protein oxidation.
AB  - Matrix metalloproteinases (MMPs) function in homeostatic and repair processes,
      but unregulated catalysis by these extracellular proteinases leads to the
      pathological destruction of tissue proteins. An important mechanism for
      controlling enzyme activity might involve hypochlorous acid (HOCl), a potent
      oxidant produced by the myeloperoxidase system of phagocytes. We have shown that
      inactivation of MMP-7 (matrilysin) by HOCl coincides with the formation of a
      novel oxidation product, WG-4, through modification of adjacent tryptophan and
      glycine residues and loss of 4 atomic mass units. Here, we use mass spectrometry,
      UV/visible spectroscopy, hydrogen-deuterium exchange, and NMR spectroscopy to
      investigate the formation and structure of WG-4. For the initial step, HOCl
      chlorinates the indole ring of tryptophan. The resulting 3-chloroindolenine
      generates a previously unknown cyclic indole-amide species, in which tryptophan
      cross-links to the main chain nitrogen of the adjacent glycine residue to form an
      aromatic six-membered ring. WG-4 kinks and stiffens the peptide backbone, which
      may hinder the interaction of substrate with the catalytic pocket of MMP-7. Our
      observations indicate that specific structural motifs are important for
      controlling protein modification by oxidants and suggest that pericellular
      oxidant production by phagocytes might limit MMP activity during inflammation.

PMID- 14670965
TI  - A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds
      angiotensin-converting enzyme 2.
AB  - The coronavirus spike (S) protein mediates infection of receptor-expressing host
      cells and is a critical target for antiviral neutralizing antibodies. Angiotensin
      converting enzyme 2 (ACE2) is a functional receptor for the coronavirus (severe
      acute respiratory syndrome (SARS)-CoV) that causes SARS. Here we demonstrate that
      a 193-amino acid fragment of the S protein (residues 318-510) bound ACE2 more
      efficiently than did the full S1 domain (residues 12-672). Smaller S protein
      fragments, expressing residues 327-510 or 318-490, did not detectably bind ACE2.
      A point mutation at aspartic acid 454 abolished association of the full S1 domain
      and of the 193-residue fragment with ACE2. The 193-residue fragment blocked S
      protein-mediated infection with an IC(50) of less than 10 nm, whereas the IC(50)
      of the S1 domain was approximately 50 nm. These data identify an independently
      folded receptor-binding domain of the SARS-CoV S protein.

PMID- 14670966
TI  - Agonist versus antagonist action of ATP at the P2Y4 receptor is determined by the
      second extracellular loop.
AB  - UTP is a potent full agonist at both the human P2Y(4) (hP2Y(4)) and rat P2Y(4)
      (rP2Y(4)) receptor. In contrast, ATP is a potent full agonist at the rP2Y(4)
      receptor but is a similarly potent competitive antagonist at the hP2Y(4)
      receptor. To delineate the structural determinants of agonism versus antagonism
      in these species homologues, we expressed a series of human/rat P2Y(4) receptor
      chimeras in 1321N1 human astrocytoma cells and assessed the capacity of ATP and
      UTP to mobilize intracellular Ca(2+). Replacement of the NH(2) terminus of the
      hP2Y(4) receptor with the corresponding region of the rP2Y(4) receptor resulted
      in a receptor that was activated weakly by ATP, whereas replacement of the second
      extracellular loop (EL2) of the hP2Y(4) receptor with that of the rP2Y(4)
      receptor yielded a chimeric receptor that was activated fully by UTP and near
      fully by ATP, albeit with lower potencies than those observed at the rP2Y(4)
      receptor. These potencies were increased, and ATP was converted to a full agonist
      by replacing both the NH(2) terminus and EL2 in the hP2Y(4) receptor with the
      corresponding regions from the rP2Y(4) receptor. Mutational analysis of the five
      divergent amino acids in EL2 between the two receptors revealed that three amino
      acids, Asn-177, Ile-183, and Leu-190, contribute to the capacity of EL2 to impart
      ATP agonism. Taken together, these results suggest that the second extracellular
      loop and the NH(2) terminus form a functional motif that plays a key role in
      determining whether ATP functions as an agonist or antagonist at mammalian P2Y(4)
      receptors.

PMID- 14670967
TI  - Mechanisms for lysophosphatidic acid-induced cytokine production in ovarian
      cancer cells.
AB  - A potential role for lysophosphatidic acid (LPA) in human oncogenesis was first
      suggested by the observation that LPA is present at elevated levels in ascites of
      ovarian cancer patients. In the current study, we demonstrated that LPA is a
      potent inducer of interleukin-6 (IL-6) and interleukin-8 (IL-8) production in
      ovarian cancer cells. Both IL-6 and IL-8 have been implicated in ovarian cancer
      progression. We characterized the IL-8 gene promoter to ascertain the
      transcriptional mechanism underlying LPA -induced expression of these cytokines.
      LPA stimulated the transcriptional activity of the IL-8 gene with little effect
      on IL-8 mRNA stability. The optimal response of the IL-8 gene promoter to LPA
      relied on binding sites for NF-kappaB and AP-1, two transcription factors that
      were strongly activated by LPA in ovarian cancer cell lines. Positive regulators
      of the NF-kappaB and AP-1 pathways synergistically activated the IL-8 gene
      promoter. Further, the effect of LPA on IL-6 and IL-8 generation is mediated by
      the Edg LPA receptors as enforced expression of LPA receptors restored LPA
      induced IL-6 and IL-8 production in non-responsive cells and enhanced the
      sensitivity to LPA in responsive cell lines. The LPA(2) receptor was identified
      to be the most efficient in linking LPA to IL-6 and IL-8 production although
      LPA(1) and LPA(3) were also capable of increasing the response to a certain
      degree. These studies elucidate the transcriptional mechanism and the Edg LPA
      receptors involved in LPA-induced IL-6 and IL-8 production and suggest potential
      strategies to restrain the expression of these cytokines in ovarian cancer.

PMID- 14670968
TI  - Kruppel-like factor 4 (KLF4) represses histidine decarboxylase gene expression
      through an upstream Sp1 site and downstream gastrin responsive elements.
AB  - Histidine decarboxylase (HDC) is the enzyme that catalyzes the conversion of
      histidine to histamine, a bioamine that plays an important role in allergic
      responses, inflammation, neurotransmission, and gastric acid secretion.
      Previously, we demonstrated that gastrin activates HDC promoter activity in a
      gastric cancer (AGS-E) cell line through three overlapping downstream promoter
      elements. In the current study, we used the yeast one-hybrid strategy to identify
      nuclear factors that bind to these three elements. Among eight positives from the
      one-hybrid screen, we identified Kruppel-like factor 4 (KLF4) (previously known
      as gut-enriched Kruppel-like factor (GKLF)) as one factor that binds to the
      gastrin responsive elements in the HDC promoter. Electrophoretic mobility shift
      assays confirmed that KLF4 is able to bind all three gastrin responsive elements.
      In addition, transient cotransfection experiments showed that overexpression of
      KLF4 dose dependently and specifically inhibited HDC promoter activity.
      Regulation of HDC transcription by KLF4 was confirmed by changes in the
      endogenous HDC messenger RNA by KLF4 small interfering RNA and KLF4
      overexpression. We further showed that KLF4 inhibits HDC promoter activity by
      competing with Sp1 at the upstream GC box and also independently by binding the
      three downstream gastrin responsive elements. Taken together, these results
      indicate that KLF4 can act to repress HDC gene expression by Sp1-dependent and 
      independent mechanisms.

PMID- 14670969
TI  - Intracellular localization and activity state of tissue transglutaminase
      differentially impacts cell death.
AB  - Tissue transglutaminase (tTG) is a unique member of the transglutaminase family
      as it is both a transamidating enzyme and a GTPase. In the cell tTG is mostly
      cytosolic, however it is also found in the nucleus and associated with the plasma
      membrane. tTG can be proapoptotic, however anti-apoptotic activities of the
      enzyme have also been reported. To determine how the intracellular localization
      and transamidating activity of tTG modulates its effects on apoptosis, HEK293
      cells were transiently transfected with tTG or [C277S]tTG (which lacks
      transamidating activity) constructs that were targeted to different intracellular
      compartments. Apoptosis was induced by thapsigargin treatment, which results in
      increased intracellular calcium concentrations. Cytosolic tTG was pro-apoptotic,
      while nuclear localization of [C277S]tTG attenuated apoptosis. Membrane-targeted
      tTG had neither pro- nor anti-apoptotic functions. This finding indicates for the
      first time that intracellular localization is an important determinant of the
      effect of tTG on apoptosis. Previous studies have suggested that tTG may modulate
      retinoblastoma (Rb) protein, an important suppressor of apoptosis. tTG interacted
      with Rb and after induction of apoptosis, the interaction of nuclear-targeted
      [C277S]tTG with Rb was increased significantly concomitant with an attenuation of
      apoptosis. In contrast, the interaction of nuclear-targeted tTG with Rb was
      significantly decreased and apoptosis was not attenuated. These data suggest that
      tTG protects cells against apoptosis in response to stimuli that do not result in
      increased transamidating activity by translocating to the nucleus, and that
      complexing with Rb may be an important aspect of the protective effects of tTG.

PMID- 14670970
TI  - Evidence for the translation initiation of leaderless mRNAs by the intact 70 S
      ribosome without its dissociation into subunits in eubacteria.
AB  - In eubacteria, the dissociation of the 70 S ribosome into the 30 S and 50 S
      subunits is the essential first step for the translation initiation of canonical
      mRNAs that possess 5'-leader sequences. However, a number of leaderless mRNAs
      that start with the initiation codon have been identified in some eubacteria.
      These have been shown to be translated efficiently in vivo. Here we investigated
      the process by which leaderless mRNA translation is initiated by using a highly
      reconstituted cell-free translation system from Escherichia coli. We found that
      leaderless mRNAs bind preferentially to 70 S ribosomes and that the leaderless
      mRNA.70 S.fMet-tRNA complex can transit from the initiation to the elongation
      phase even in the absence of initiation factors (IFs). Moreover, leaderless mRNA
      translation proceeds more efficiently if the intact 70 S ribosome is involved
      compared with the 30 S subunit. Furthermore, excess amounts of IF3 inhibit
      leaderless mRNA translation, probably because it promotes the disassembly of the
      70 S ribosome into subunits. Finally, excess amounts of fMet-tRNA facilitate the
      IF-independent translation of leaderless mRNA. These observations strongly
      suggest that leaderless mRNA translation is initiated by the assembled 70 S
      ribosome and thereby bypasses the dissociation process.

PMID- 14670971
TI  - The linear pentadecapeptide gramicidin is assembled by four multimodular
      nonribosomal peptide synthetases that comprise 16 modules with 56 catalytic
      domains.
AB  - Linear gramicidin is a membrane channel forming pentadecapeptide that is produced
      via the nonribosomal pathway. It consists of 15 hydrophobic amino acids with
      alternating l- and d-configuration forming a beta-helix-like structure. It has an
      N-formylated valine and a C-terminal ethanolamine. Here we report cloning and
      sequencing of the entire biosynthetic gene cluster as well as initial biochemical
      analysis of a new reductase domain. The biosynthetic gene cluster was identified
      on two nonoverlapping fosmids and a 13-kilobase pair (kbp) interbridge fragment
      covering a region of 74 kbp. Four very large open reading frames, lgrA, lgrB,
      lgrC, and lgrD with 6.8, 15.5, 23.3, and 15.3 kbp, were identified and shown to
      encode nonribosomal peptide synthetases with two, four, six, and four modules,
      respectively. Within the 16 modules identified, seven epimerization domains in
      alternating positions were detected as well as a putative formylation domain
      fused to the first module LgrA and a putative reductase domain attached to the C
      terminal module of LgrD. Analysis of the substrate specificity by phylogenetic
      studies using the residues of the substrate-binding pockets of all 16 adenylation
      domains revealed a good agreement of the substrate amino acids predicted with the
      sequence of linear gramicidin. Additional biochemical analysis of the three
      adenylation domains of modules 1, 2, and 3 confirmed the colinearity of this
      nonribosomal peptide synthetase assembly line. Module 16 was predicted to
      activate glycine, which would then, being the C-terminal residue of the peptide
      chain, be reduced by the adjacent reductase domain to give ethanolamine, thereby
      releasing the final product N-formyl-pentadecapeptide-ethanolamine. However,
      initial biochemical analysis of this reductase showed only a one-step reduction
      yielding the corresponding aldehyde in vitro.

PMID- 14670972
TI  - Cathepsin S supports acid-independent infection by some reoviruses.
AB  - In murine fibroblasts, efficient proteolysis of reovirus outer capsid protein
      sigma3 during cell entry by virions requires the acid-dependent lysosomal
      cysteine protease cathepsin L. The importance of cathepsin L for infection of
      other cell types is unknown. Here we report that the acid-independent lysosomal
      cysteine protease cathepsin S mediates outer capsid processing in macrophage-like
      P388D cells. P388D cells supported infection by virions of strain Lang, but not
      strain c43. Genetic studies revealed that this difference is determined by S4,
      the viral gene segment that encodes sigma3. c43-derived subvirion particles that
      lack sigma3 replicated normally in P388D cells, suggesting that the difference in
      infectivity of Lang and c43 virions is at the level of sigma3 processing.
      Infection of P388D cells with Lang virions was inhibited by the broad spectrum
      cysteine protease inhibitor trans-epoxysuccinyl-l-leucylamido-(4-guanidino)butane
      but not by NH(4)Cl, which raises the endocytic pH and thereby inhibits acid
      dependent proteases such as cathepsins L and B. Outer capsid processing and
      infection of P388D cells with Lang virions were also inhibited by a cathepsin S
      specific inhibitor. Furthermore, in the presence of NH(4)Cl, cell lines
      engineered to express cathepsin S supported infection by Lang, but not c43,
      virions. Our results thus indicate that differences in susceptibility to
      cathepsin S-mediated sigma3 processing are responsible for strain differences in
      reovirus infection of macrophage-like P388D cells and other cathepsin S
      expressing cells. Additionally, our data suggest that the acid dependence of
      reovirus infections of most other cell types may reflect the low pH requirement
      for the activities of most other lysosomal proteases rather, than some other acid
      dependent aspect of cell entry.

PMID- 14670973
TI  - The dominant role of Sp1 in regulating the cystathionine beta-synthase -1a and 
      1b promoters facilitates potential tissue-specific regulation by Kruppel-like
      factors.
AB  - Cystathionine beta-synthase (CBS) catalyzes the condensation of serine with
      homocysteine to form cystathionine and occupies a crucial regulatory position
      between the methionine cycle and transsulfuration. The human cystathionine beta
      synthase gene promoters -1a and -1b are expressed in a limited number of tissues
      and are coordinately regulated with proliferation through a redox-sensitive
      mechanism. Site-directed mutagenesis, DNase I footprinting and deletion analysis
      of 5276 bp of 5' proximal -1b flanking sequence revealed that this region does
      not confer tissue-specific expression and that 210 bp of proximal sequence is
      sufficient for maximal promoter activity. As little as 32 bp of the -1b proximal
      promoter region is capable of driving transcription in HepG2 cells, and this
      activity is entirely dependent upon the presence of a single overlapping Sp1/Egr1
      binding site. Co-transfection studies in Drosophila SL2 cells indicated that both
      promoters are transactivated by Sp1 and Sp3 but only the -1b promoter is subject
      to a site-specific synergistic regulatory interaction between Sp1 and Sp3. Sp1
      deficient fibroblasts expressing both Sp3 and NF-Y were negative for CBS
      activity. Transfection of these cells with a mammalian Sp1 expression construct
      induced high levels of CBS activity indicating that Sp1 has a critical and
      indispensable role in the regulation of cystathionine beta-synthase. Sp1 binding
      to both CBS promoters is sensitive to proliferation status and is negatively
      regulated by Kruppel-like factors in co-transfection experiments suggesting a
      possible mechanism for the tissue specific regulation of cystathionine beta
      synthase.

PMID- 14670974
TI  - Structurally homologous binding of plant calmodulin isoforms to the calmodulin
      binding domain of vacuolar calcium-ATPase.
AB  - The discovery that plants contain multiple calmodulin (CaM) isoforms having
      variable sequence identity to mammalian CaM has sparked a flurry of new questions
      regarding the intracellular role of Ca(2+) regulation in plants. To date, the
      majority of research in this field has focused on the differential enzymatic
      regulation of various mammalian CaM-dependent enzymes by the different plant CaM
      isoforms. However, there is comparatively little information on the structural
      recognition of target enzymes found exclusively in plant cells. Here we have used
      a variety of spectroscopic techniques, including nuclear magnetic resonance,
      circular dichroism, and fluorescence spectroscopy, to study the interactions of
      the most conserved and most divergent CaM isoforms from soybean, SCaM-1, and SCaM
      4, respectively, with a synthetic peptide derived from the CaM-binding domain of
      cauliflower vacuolar calcium-ATPase. Despite their sequence divergence, both SCaM
      1 and SCaM-4 interact with the calcium-ATPase peptide in a similar calcium
      dependent, stoichiometric manner, adopting an antiparallel binding orientation
      with an alpha-helical peptide. The single Trp residue is bound in a solvent
      inaccessible hydrophobic pocket on the C-terminal domain of either protein.
      Thermodynamic analysis of these interactions using isothermal titration
      calorimetry demonstrates that the formation of each calcium-SCaM-calcium-ATPase
      peptide complex is driven by favorable binding enthalpy and is very similar to
      the binding of mammalian CaM to the CaM-binding domains of myosin light chain
      kinases and calmodulin-dependent protein kinase I.

PMID- 14670975
TI  - A short-range gradient of histone H3 acetylation and Tup1p redistribution at the
      promoter of the Saccharomyces cerevisiae SUC2 gene.
AB  - Chromatin immunoprecipitation assays are used to map H3 and H4 acetylation over
      the promoter nucleosomes and the coding region of the Saccharomyces cerevisiae
      SUC2 gene, under repressed and derepressed conditions, using wild type and mutant
      strains. In wild type cells, a high level of H3 acetylation at the distal end of
      the promoter drops sharply toward the proximal nucleosome that covers the TATA
      box, a gradient that become even steeper on derepression. In contrast,
      substantial H4 acetylation shows no such gradient and extends into the coding
      region. Overall levels of both H3 and H4 acetylation rise on derepression.
      Mutation of GCN5 or SNF2 lead to substantially reduced SUC2 expression; in gnc5
      there is no reduction in basal H3 acetylation, but large reductions occur on
      derepression. SNF2 mutation has little effect on H3 acetylation, so SAGA and
      SWI/SNF recruitment seem to be independent events. H4 acetylation is little
      affected by either GCN5 or SNF2 mutation. In a double snf2/gcn5 mutant (very low
      SUC2 expression), H3 acetylation is at the minimal level, but H4 acetylation
      remains largely unaffected. Transcription is thus linked to H3 but not H4
      acetylation. Chromatin immunoprecipitation assays show that Tup1p is evenly
      distributed over the four promoter nucleosomes in repressed wild type cells but
      redistributes upstream on derepression, a movement probably linked to its
      conversion from a repressor to an activator.

PMID- 14670976
TI  - Deactylase inhibitors disrupt cellular complexes containing protein phosphatases
      and deacetylases.
AB  - Affinity isolation of protein serine/threonine phosphatases on the immobilized
      phosphatase inhibitor microcystin-LR identified histone deacetylase 1(HDAC1),
      HDAC6, and HDAC10 as novel components of cellular phosphatase complexes. Other
      HDACs, specifically HDAC2, -3, -4, and -5, were excluded from such complexes. In
      vitro biochemical studies showed that recombinant HDAC6, but not HDAC4, bound
      directly to the protein phosphatase (PP)1 catalytic subunit. No association was
      observed between HDAC6 and PP2A, another major protein phosphatase. PP1 binding
      was mapped to the second catalytic domain and adjacent C-terminal sequences in
      HDAC6, and treatment of cells with trichostatin A (TSA) disrupted endogenous
      HDAC6.PP1 complexes. Consistent with the inhibition of tubulin deactylase
      activity of HDAC6, TSA enhanced cellular tubulin acetylation, and acetylated
      tubulin was present in the PP1 complexes from TSA-treated cells. Trapoxin B, a
      weak HDAC6 inhibitor, and calyculin A, a cell-permeable phosphatase inhibitor,
      had no effect on the stability of the HDAC6.PP1 complexes or on tubulin
      acetylation. Mutations that inactivated HDAC6 prevented its incorporation into
      cellular PP1 complexes and suggested that when bound together both enzymes were
      active. Interestingly, TSA disrupted all the cellular HDAC.phosphatase complexes
      analyzed. This study provided new insight into the mechanism by which HDAC
      inhibitors elicited coordinate changes in cellular protein phosphorylation and
      acetylation and suggested that changes in these protein modifications at multiple
      subcellular sites may contribute to the known ability of HDAC inhibitors to
      suppress cell growth and transformation.

PMID- 14670977
TI  - The crystal structure of pectate lyase Pel9A from Erwinia chrysanthemi.
AB  - The "family 9 polysaccharide lyase" pectate lyase L (Pel9A) from Erwinia
      chrysanthemi comprises a 10-coil parallel beta-helix domain with distinct
      structural features including an asparagine ladder and aromatic stack at novel
      positions within the superhelical structure. Pel9A has a single high affinity
      calcium-binding site strikingly similar to the "primary" calcium-binding site
      described previously for the family Pel1A pectate lyases, and there is strong
      evidence for a common second calcium ion that binds between enzyme and substrate
      in the "Michaelis" complex. Although the primary calcium ion binds substrate in
      subsite -1, it is the second calcium ion, whose binding site is formed by the
      coming together of enzyme and substrate, that facilitates abstraction of the C5
      proton from the sacharride in subsite +1. The role of the second calcium is to
      withdraw electrons from the C6 carboxylate of the substrate, thereby acidifying
      the C5 proton facilitating its abstraction and resulting in an E1cb-like anti
      beta-elimination mechanism. The active site geometries and mechanism of Pel1A and
      Pel9A are closely similar, but the catalytic base is a lysine in the Pel9A
      enzymes as opposed to an arginine in the Pel1A enzymes.

PMID- 14670978
TI  - Amino acid residues in RAG1 responsible for the interaction with RAG2 during the
      V(D)J recombination process.
AB  - The V(D)J recombinase, a complex of RAG1 and RAG2, carries out a gene
      rearrangement process that is required for the achievement of diverse antigen
      receptor repertoires during the early developmental stage of lymphocytes. It
      recognizes a specific site spanning the coding DNA region of antigen receptor
      genes and produces double-stranded DNA breaks at the board between coding and
      signal sequences. Two broken DNA ends are joined by a double-stranded break
      repair system. Both RAG (recombination activation gene) 1 and RAG2 proteins are
      absolutely required for this process although the catalytic residues of V(D)J
      recombinase are exclusively located at RAG1 according to recent mutational
      analyses. In this study we identified some acidic amino acid residues in RAG1
      responsible for the interaction with RAG2. Mutation on these residues caused a
      decrease of cleavage activity in vitro and failure of RAG-RSS DNA synaptic
      complex formation. This result is complementary to previous reports in which
      positively charged amino acids in RAG2 play an important role in RAG1 binding.

PMID- 14670982
TI  - Minireview: Sex differences in adult and developing brains: compensation,
      compensation, compensation.
AB  - Despite decades of research, we do not know the functional significance of most
      sex differences in the brain. We are heavily invested in the idea that sex
      differences in brain structure cause sex differences in behavior. We rarely
      consider the possibility that sex differences in brain structure may also prevent
      sex differences in overt functions and behavior, by compensating for sex
      differences in physiological conditions, e.g. gonadal hormone levels that may
      generate undesirable sex differences if left unchecked. Such a dual function for
      sex differences is unlikely to be restricted to adult brains. This review will
      entertain the possibility that transient sex differences in gene expression in
      developing brains may cause permanent differences in brain structure but prevent
      them as well, by compensating for potentially differentiating effects of sex
      differences in gonadal hormone levels and sex chromosomal gene expression.
      Consistent application of this dual-function hypothesis will make the search for
      the functional significance of sex differences more productive.

PMID- 14670979
TI  - Role of prostaglandin E receptor EP1 subtype in the development of renal injury
      in genetically hypertensive rats.
AB  - One of the major causes of end-stage renal diseases is hypertensive renal
      disease, in which enhanced renal prostaglandin (PG) E2 production has been shown.
      PGE2, a major arachidonic acid metabolite produced in the kidney, acts on 4
      receptor subtypes, EP1 through EP4, but the pathophysiological importance of the
      PGE2/EP subtypes in the development of hypertensive renal injury remains to be
      elucidated. In this study, we investigated whether an orally active EP1-selective
      antagonist (EP1A) prevents the progression of renal damage in stroke-prone
      spontaneously hypertensive rats (SHRSP), a model of human malignant hypertension.
      Ten-week-old SHRSP, with established hypertension but with minimal renal damage,
      were given EP1A or vehicle for 5 weeks. After the treatment period, vehicle
      treated SHRSP showed prominent proliferative lesions in arterioles, characterized
      by decreased alpha-smooth muscle actin expression in multilayered vascular smooth
      muscle cells. Upregulation of transforming growth factor-beta expression and
      tubulointerstitial fibrosis were also observed in vehicle-treated SHRSP. All
      these changes were dramatically attenuated in EP1A-treated SHRSP. Moreover, EP1A
      treatment significantly inhibited both increase in urinary protein excretion and
      decrease in creatinine clearance but had little effect on systemic blood
      pressure. These findings indicate that the PGE2/EP1 signaling pathway plays a
      crucial role in the development of renal injury in SHRSP. This study opens a
      novel therapeutic potential of selective blockade of EP1 for the treatment of
      hypertensive renal disease.

PMID- 14670983
TI  - Minireview: Sex chromosomes and brain sexual differentiation.
AB  - The brains of males and females differ, not only in regions specialized for
      reproduction, but also in other regions (controlling cognition, for example)
      where sex differences are not necessarily expected. Moreover, males and females
      are differentially susceptible to neurological and psychiatric disease. What are
      the origins of these sex differences? Two major sources of sexually dimorphic
      information could lead to sex differences in brain function. Male and female
      brain cells carry a different complement of sex chromosome genes and are
      influenced throughout life by a different mix of gonadal hormones. Until recently
      all sex differences in the brain have been attributed to the differential action
      of gonadal hormones. Recent findings, however, suggest that brain cells that
      differ in their genetic sex are not equivalent, and that difference may
      contribute to sex differences in brain function. Here we discuss evidence for sex
      chromosome effects on both neural and nonneural systems, which together provide
      support for the idea that XX and XY cells differentiate even before they are
      influenced by gonadal hormones, and even if they are exposed to similar levels of
      gonadal steroids. Fortunately, new model systems for studying sex chromosome
      effects have recently been developed, and they should help in testing further the
      role of sex chromosome genes.

PMID- 14670984
TI  - Minireview: Neuronal steroid hormone receptors: they're not just for hormones
      anymore.
AB  - The ovarian steroid hormones have numerous effects on the brain, many of which
      are mediated, at least in part, by interaction with intracellular steroid hormone
      receptors acting as regulators of transcription. These intracellular steroid
      hormone receptors have often been considered to be activated solely by cognate
      hormone. However, during the past decade, numerous studies have shown that the
      receptors can be activated by neurotransmitters and intracellular signaling
      systems, through a process that does not require hormone. Although most of these
      have been in vitro experiments, others have been in vivo. Evidence from a wide
      variety of tissues and cells suggests that steroid hormone receptors are
      transcription factors that can be activated by a wide variety of factors, only
      one of which is cognate hormone. Furthermore, ligand-independent activation of
      neural steroid hormone receptors, rather than being a pharmacological or in vitro
      curiosity, seems to be a process that occurs in the normal physiology of animals.
      Thinking of steroid hormone receptors only as ligand-activated proteins may
      constrain our thinking about the many factors that may activate the receptors and
      cause receptor-dependent changes in neural gene expression and neuroendocrine
      function.

PMID- 14670985
TI  - Transforming growth factor beta1 may directly influence gonadotropin-releasing
      hormone gene expression in the rat hypothalamus.
AB  - In vitro studies using immortalized GT1 cells suggest that hypothalamic
      astrocytes employ TGFbeta(1) to directly regulate the secretion of GnRH, the
      neurohormone that controls sexual maturation and adult reproductive function.
      However, whether such astrocyte-GnRH neuron signaling occurs in vivo is not
      clear. In the present study, we used in situ hybridization and
      immunohistochemistry to determine whether astrocytes and GnRH neurons express the
      molecular components necessary to set in motion communication processes involving
      TGFbeta(1) signaling. Double-labeling experiments showed that astrocytes in the
      male rat preoptic region (POA) expressed TGFbeta(1) mRNA and that GnRH perikarya
      were often found in close association with TGFbeta(1) mRNA-expressing cells. In
      addition, GnRH neuronal cell bodies in the POA expressed both type II TGFbeta
      receptors (TGFbeta-RII), which selectively bind TGFbeta, and Smad2/3, one of the
      primary transducers of TGFbeta signaling, suggesting that they are fully capable
      of responding directly to TGFbeta(1) stimulation. Consistent with this
      hypothesis, incubation of POA explants with TGFbeta(1) caused a significant, dose
      dependent decrease in GnRH mRNA expression in individual neurons. This effect was
      observed within 1 h after TGFbeta(1)-treatment and was inhibited by addition of
      the soluble form of TGFbeta-RII to the incubation medium. In contrast, whereas
      both TGFbeta(1) and TGFbeta-RII mRNAs were abundantly expressed in both glial
      cells and capillaries in the median eminence, the projection field of GnRH
      neurons, TGFbeta-RII immunoreactivity was mainly restricted to the processes of
      tanycytes and did not colocalize with GnRH-immunoreactive fibers. This
      observation supports previous in vivo studies showing that TGFbeta(1) is unable
      to directly modulate decapeptide release from GnRH nerve terminals. Thus,
      astrocyte-derived TGFbeta(1) may directly influence GnRH expression and/or
      secretion in vivo by acting on the perikarya, but not the terminals, of GnRH
      neurons.

PMID- 14670986
TI  - Minireview: A plethora of estrogen receptors in the brain: where will it end?
AB  - Until 1996, when estrogen receptor (ER)-beta was discovered, life seemed simple.
      The gonadal steroid hormone 17 beta-estradiol had one receptor, the ER, a ligand
      inducible nuclear transcription factor. ER variants, the result of base pair
      insertions, transitions, and deletions, as well as alternative splicing, were
      considered abnormal and a prominent feature of breast cancer. Since then, like
      many other scientific beliefs, this concept has increased dramatically in
      complexity, and we are now faced with an ever-increasing array of estrogen
      binding proteins, putative ERs, in the brain as well as in the extraneural
      targets of estrogen. The end is unlikely to be in sight. Some of these putative
      receptors have been localized to plasma or nuclear membranes, and others to the
      cytoplasm and/or nucleus. The molecular characteristics of membrane ERs are still
      in question, and, in most instances, the proteins have not been sequenced or
      cloned. However, based on transfection and immunohistochemistry, the generally
      held view, if not dogma, maintains that both nuclear and plasma membrane
      associated ERs probably originate from the same gene and transcript that produce
      the classical intranuclear receptors ER-alpha and ER-beta. However, the
      physiological relatedness of this observation remains open to question. This
      review addresses evidence that, in addition to ER-alpha and ER-beta, there exist
      a variety of non-ER-alpha/non-ER-beta nuclear, cytoplasmic, and plasma membrane
      ERs in the brain, including G protein-coupled receptors; a novel, developmentally
      regulated, membrane-associated ER, ER-X; a functional, truncated ER-alpha
      variant, ER-46; and a putative ER that is immunochemically, structurally, and
      functionally completely distinct from ER-alpha and ER-beta.

PMID- 14670987
TI  - Sphingolipid-cholesterol domains (lipid rafts) in normal human and dog thyroid
      follicular cells are not involved in thyrotropin receptor signaling.
AB  - Partition of signaling molecules in sphingolipid-cholesterol-enriched membrane
      domains, among which are the caveolae, may contribute to signal transduction
      efficiency. In normal thyroid, nothing is known about a putative TSH/cAMP cascade
      compartmentation in caveolae or other sphingolipid-cholesterol-enriched membrane
      domains. In this study we show for the first time that caveolae are present in
      the apical membrane of dog and human thyrocytes: caveolin-1 mRNA presence is
      demonstrated by Northern blotting in primary cultures and that of the caveolin-1
      protein by immunohistochemistry performed on human thyroid tissue. The TSH
      receptor located in the basal membrane can therefore not be located in caveolae.
      We demonstrate for the first time by biochemical methods the existence of
      sphingolipid-cholesterol-enriched domains in human and dog thyroid follicular
      cells that contain caveolin, flotillin-2, and the insulin receptor. We assessed a
      possible sphingolipid-cholesterol-enriched domains compartmentation of the TSH
      receptor and the alpha- subunit of the heterotrimeric G(s) and G(q) proteins
      using two approaches: Western blotting on detergent-resistant membranes isolated
      from thyrocytes in primary cultures and the influence of 10 mm methyl-beta
      cyclodextrin, a cholesterol chelator, on basal and stimulated cAMP accumulation
      in intact thyrocytes. The results from both types of experiments strongly suggest
      that the TSH/cAMP cascade in thyroid cells is not associated with sphingolipid
      cholesterol-enriched membrane domains.

PMID- 14670988
TI  - Dietary-induced obesity and hypothalamic infertility in female DBA/2J mice.
AB  - The effects of diet and adiposity have been implicated in disturbances of female
      reproductive function. In an effort to better elucidate the relationship between
      obesity and female fertility, we analyzed the effect of increasing dietary fat
      content on body composition, insulin sensitivity, and pregnancy rates in two
      common inbred mouse strains, DBA/2J and C57BL/6J. After 16 wk, females of both
      strains on the high fat diet developed glucose intolerance and insulin
      resistance, but only the female DBA/2J mice developed dietary-induced obesity and
      hyperleptinemia. The high fat diet was associated with more than a 60% decrease
      in natural pregnancy rates of female DBA/2J mice, whereas the fertility of female
      C57BL/6J mice was unaffected. Despite developing a similar degree of obesity,
      insulin resistance, and hyperleptinemia, male DBA/2J mice did not manifest
      diminished fertility. Obese female DBA/2J mice achieved normal ovulatory
      responses and pregnancy rates after exogenous gonadotropin stimulation,
      suggesting their fertility defect to be central in origin. Real-time PCR
      quantification of hypothalamic cDNA revealed a 100% up-regulation of neuropeptide
      Y and a 50% suppression of GnRH expression accompanied by a 95% attenuation of
      leptin receptor type B expression in obese female DBA/2J mice. These findings
      suggest that obesity-associated hyperleptinemia, and not insulin resistance or
      increased dietary fat per se, gradually induces central leptin resistance,
      increases hypothalamic neuropeptide Y-ergic tone, and ultimately causes
      hypothalamic hypogonadism. The data establish high fat-fed female DBA/2J mice as
      a wild-type murine model of obesity-related infertility.

PMID- 14670989
TI  - Minireview: Role of glia in neuroendocrine function.
AB  - Long relegated to the backwaters of neuroendocrinology, it is becoming
      increasingly apparent that glial cells of the central and peripheral nervous
      system are key participants because they are capable of both sending and
      receiving hormonal signals. Hormones are also a critical component of
      neuronal/glial cross talk, leading to neuromodulatory and neurotrophic actions
      under physiological and pathological conditions. In the peripheral nervous
      system, hormonal actions on Schwann cells and hormonal metabolites produced by
      these glial cells promote myelin formation and the remyelination and regeneration
      of injured nerves. In the central nervous system, glial cells participate in the
      hormonal regulation of synaptic function, synaptic plasticity, myelin formation,
      cognition, sleep, and the response of nervous tissue to injury. In addition,
      central glial cells participate in the regulation of hormonal secretion by
      hypothalamic neurons. Therefore, glial cells are a key element to understanding
      hormonal actions in the nervous system and the regulation of neuroendocrine
      events.

PMID- 14670990
TI  - Gender-specific pattern of insulin-like growth factor-binding protein-3 protease
      activity in mouse thyroid.
AB  - There is evidence that the IGF system plays an important role in the growth and
      function of the thyroid gland. Proteolysis is an important posttranslational
      process that modulates the affinity of IGF binding proteins (IGFBPs) to IGFs,
      thus regulating their activity. IGFBP-3 has been shown to be cleaved by members
      of the kallikrein family, some of which are expressed in human thyroid and are
      characterized by regulation by steroid hormones. The aim of this study was to
      determine whether IGFBP-3 protease activity is present in mouse thyroid tissue
      and to characterize its activity by gender and nutrition. Male and female BALB/c
      mice, aged 16 wk, were studied in the fasted state, or after 1-h or 4-h
      refeeding. IGFBP protease activity was present in thyroid tissue and resulted in
      a decrease in IGFBP-3 affinity for IGF-I. The activity was inhibited by 10 mM
      ZnCl(2), activated by CaCl(2), and was substantially greater in tissue from male
      mice compared with that from female animals. These properties and the pattern of
      effect of a panel of protease inhibitors were consistent with this protease being
      a member of the tissue kallikrein family. Serum inhibited the proteolytic effect
      of thyroid extracts. There was no effect of nutrition. In conclusion, the degree
      of activity of IGFBP-3 protease in mouse thyroid tissue is gender specific and is
      likely to lead to an increased IGF availability in male mice.

PMID- 14670991
TI  - Peroxisomal proliferator-activated receptor alpha deficiency diminishes insulin
      responsiveness of gluconeogenic/glycolytic/pentose gene expression and substrate
      cycle flux.
AB  - Our previous work led to the hypothesis that peroxisomal proliferator-activated
      receptor alpha (PPAR alpha) modulates insulin action in a compensatory fashion
      for hepatic glucose balance vs. peripheral glucose disposal. Therefore, we have
      examined the expression of insulin-dependent gluconeogenic/glycolytic/pentose
      cycle enzymes and compared these to insulin responsiveness for peripheral vs.
      hepatic substrate flux and futile cycling in the PPAR alpha knockout mouse.
      Hepatic gluconeogenic flux, glucose absorption, clearance and recycling, as well
      as in vivo glucose disposal were evaluated using new mass isotopomer methods.
      Insulin-dependent gluconeogenic/glycolytic/pentose cycle enzyme expression and
      glucose futile cycling were diminished; however, glucose disappearance was
      increased. This supports the hypothesis of hepatic insulin resistance and
      increased peripheral glucose uptake as compensatory events secondary to the
      decrease in fatty acid oxidation characteristic of the PPAR alpha knockout. We
      conclude that 1) the loss of PPAR alpha results in lower expression levels and
      diminished response to meal regulation for gluconeogenic/glycolytic enzyme
      expression; and 2) consequently, substrate/futile cycling of glucose is decreased
      when PPAR alpha is absent despite increased gluconeogenesis. The compensatory
      changes in liver and peripheral tissue substrate flux and the resultant
      adaptation for enzyme expression in the liver to have a diminished insulin
      dependence reflect the loosely linked correlation between phenotype and genotype
      in hepatic glucose metabolism.

PMID- 14670992
TI  - Developmental expression and subcellular localization of mouse MATER, an oocyte
      specific protein essential for early development.
AB  - We reported previously that Mater is a maternal effect gene that is required for
      early embryonic development beyond the two-cell stage in mice. Here we show the
      expressional profile of Mater and its protein during oogenesis and embryogenesis
      as well as its subcellular localization in oocytes. Mater mRNA was detectable
      earliest in oocytes of type 2 follicles, whereas MATER protein appeared earliest
      in oocytes of type 3a primary follicles. Both mRNA and protein accumulated during
      oocyte growth. In situ hybridization showed that Mater mRNA appeared
      progressively less abundant in oocytes beyond type 5a primary follicles. By
      ribonuclease protection assay, Mater mRNA was abundant in germinal vesicle
      oocytes, but was undetectable in all stages of preimplantation embryos. In
      contrast, the protein persisted throughout preimplantation development.
      Immunogold electron microscopic analysis revealed that MATER was located in
      oocyte mitochondria and nucleoli, and close to nuclear pores. Taken together, our
      data indicate that Mater gene transcription and protein translation are active
      during oogenesis, but appear inactive during early embryogenesis. Thus, Mater and
      its protein are expressed in a manner typical of maternal effect genes. The
      presence of MATER protein in mitochondria and nucleoli suggests that it may
      participate in both cytoplasmic and nuclear events during early development.

PMID- 14670993
TI  - Targeted expression of calmodulin increases ventricular cardiomyocyte
      proliferation and deoxyribonucleic acid synthesis during mouse development.
AB  - The cell signaling pathways that control ventricular cardiomyocyte proliferation
      during development are poorly understood. Here we show that increasing levels of
      the ubiquitous Ca(2+) receptor calmodulin (CaM) can regulate cardiomyocyte
      proliferation in vivo. Targeted overexpression of calmodulin in the heart during
      embryonic development leads to a 37% or a 79% increase in the number of
      ventricular myocytes present at embryonic d 17 in mice heterozygous or homozygous
      for the transgene, respectively. Whereas all homozygous mice die within 10 d
      after birth, most of the heterozygous mice survive even though they contain 40%
      more ventricular myocytes relative to the wild-type mice throughout development
      and into adulthood. The CaM transgene continues to be overexpressed postnatally
      and, although cell proliferation ceases soon after birth, the elevated levels of
      CaM lead to an increase in DNA synthesis, which correlates with an increase in
      the degree of ventricular myocyte polyploidy. Only after proliferation has ceased
      and polyploidy has become maximal does the continued presence of overexpressed
      CaM lead to ventricular hypertrophy. However, unlike the case for myocyte number,
      turning off expression of the CaM transgene results in regression of the
      hypertrophic response. Together, our results reveal that excess CaM enhances the
      extent of cell proliferation and DNA synthesis as well as development of
      hypertrophy of ventricular myocytes in vivo, in a manner consistent with the
      normal timing of these events during heart development.

PMID- 14670994
TI  - Apelin, a new enteric peptide: localization in the gastrointestinal tract,
      ontogeny, and stimulation of gastric cell proliferation and of cholecystokinin
      secretion.
AB  - Apelin is a recently discovered peptide that is the endogenous ligand for the APJ
      receptor. The aim of this study was to characterize apelin expression (mRNA
      levels) in the rat gastrointestinal tract and pancreas, to localize distribution
      of apelin peptide-containing cells in the stomach by immunohistochemistry, and to
      characterize the ontogeny of gastric apelin expression and peptide and the
      influence of apelin on gastric cell proliferation in vitro. Additionally, the
      effect of apelin on cholecystokinin (CCK) secretion and the involvement of MAPK,
      protein kinase C, and changes in intracellular Ca(2+) in apelin-induced CCK
      secretion in vitro were examined. Northern analysis showed a maximal apelin
      expression in the stomach with a lower expression level in the intestine. Apelin
      expression was not detected in the pancreas. Immunohistochemistry revealed
      abundant apelin-positive cells in the glandular epithelium of the stomach. The
      ontogeny study showed a higher apelin expression in the fetal and postnatal rat
      stomachs when compared with the adult stomach. In contrast to apelin expression,
      apelin peptide was not detected in the rat stomach until 20 d of age and then
      increased progressively with age. Apelin was shown to stimulate gastric cell
      proliferation in vitro. Apelin also stimulated CCK secretion from a murine
      enteroendocrine cell line (STC-1); apelin-stimulated CCK secretion is mediated
      through MAPK but not by intracellular Ca(2+) signaling. Together, these data
      indicate that apelin is an important new stomach peptide with a potential
      physiological role in the gastrointestinal tract.

PMID- 14670995
TI  - Specificity and regulation of extracellularly regulated kinase1/2 phosphorylation
      through corticotropin-releasing factor (CRF) receptors 1 and 2beta by the
      CRF/urocortin family of peptides.
AB  - Corticotropin-releasing factor (CRF) receptor (CRFR)-mediated activation of the
      ERKs 1/2-p42 and -44) has been reported for CRF, urocortin (Ucn)-I, and
      sauvagine. Recently two new members of the CRF/Ucn family of peptides have been
      identified, Ucn-II/stresscopin-related peptide and Ucn-III/stresscopin. Using
      Chinese hamster ovary cells stably expressing CRFR1 and CRFR2beta, we show that
      Ucn-I, Ucn-II and Ucn-III activate ERK1/2-p42, 44 via CRFR2beta. CRF and Ucn-I
      but not Ucn-II or Ucn-III activates ERK1/2-p42, 44 in Chinese hamster ovary cells
      stably expressing CRFR1. The selectivity of the ligands for CRFR1 and CRFR2beta
      is shown in a time- and dose-dependent manner. The regulatory mechanisms for
      ERK1/2-p42, 44 activation by both receptor types are dependent on
      phosphatidylinositol-3 OH kinase, MAPK kinase 1, and phospholipase C. Raf-1
      kinase, tyrosine kinases, and possibly intracellular Ca(2+) provide regulatory
      roles for Ucn-I activation of ERK1/2-p42, 44 by CRFR1 and CRFR2beta. Studies of
      the regulation of ERK1/2-p42, 44 by Ucn-I were extended to cell lines that
      endogenously express CRFR1 (AtT-20 and CATHa cells) and CRFR2 (A7r5 and CATHa
      cells). Use of the G(i) and G(o) protein inhibitor pertussis toxin showed that
      ERK1/2-p42, 44 activation by Ucn-I via CRFR1 and CRFR2beta are both G(i) and/or
      G(o) protein dependent. Based on the data in this study, we present putative
      signaling pathways by which the CRF/Ucn family of peptides activate ERK1/2-p42,
      44 by CRFRs.

PMID- 14670996
TI  - Peroxisome proliferator-activated receptor-alpha deficiency does not alter
      insulin sensitivity in mice maintained on regular or high-fat diet:
      hyperinsulinemic-euglycemic clamp studies.
AB  - Chronic peroxisome proliferator-activated receptor (PPAR)-alpha activation
      improves glucose metabolism in rodent models of insulin resistance and diabetes;
      however, PPAR-alpha deficiency was also reported to protect against high-fat diet
      (HFD)-induced insulin resistance. The aim of this study was to clarify the role
      of PPAR-alpha in the development of insulin resistance using PPAR-alpha knockout
      (KO) mice and wild-type controls (WT). Both WT and PPAR-alpha KO mice on HFD
      gained significantly more weight relative to chow-fed groups and displayed an
      increase in insulin levels and a decrease in adiponectin levels. Hyperinsulinemic
      euglycemic clamp performed in the nonfasting state demonstrated that HFD caused a
      marked reduction in whole body, muscle, and white and brown adipose tissue
      glucose uptake in both WT and PPAR-alpha KO mice relative to chow-fed groups.
      Suppression of endogenous glucose production during the clamp was markedly
      blunted in both WT and PPAR-alpha KO HFD-fed mice, indicating liver insulin
      resistance. The magnitude of HFD-induced changes in the clamp parameters of
      insulin sensitivity was comparable in PPAR-alpha KO and WT mice. In conclusion,
      these data show that PPAR-alpha deficiency does not alter insulin sensitivity in
      mice fed normal chow diet and does not protect against HFD-induced insulin
      resistance as measured by hyperinsulinemic-euglycemic clamp in nonfasted state.

PMID- 14670997
TI  - Folliculostellate cells determine the susceptibility of lactotropes to
      estradiol's mitogenic action.
AB  - Estradiol is known to increase lactotropic cell proliferation, but estradiol
      susceptibility varies among human populations and among various strains of rats.
      We had reported that folliculostellate (FS) cells regulate estradiol's mitogenic
      action on lactotropes; therefore, we studied their role in determining the
      susceptibility to estradiol in a high estradiol-responsive rat strain, Fischer
      344 (F344), and in a low-responsive strain, Sprague Dawley (SD). Determination of
      total S-100-positive FS cells in the pituitary revealed that F344 rats have
      significantly more FS cells than do SD rats. Estradiol treatment did not change
      the number of FS cells in both F344 and SD rats. When cotransplanted with F344
      pituitaries under the kidney capsule or cocultured with F344-derived lactotropes
      in vitro, FS cells derived from F344 rats increased estradiol's mitogenic action.
      They also increased estradiol's mitogenic action on SD-derived lactotropes in
      primary cultures. However, SD-derived FS cells failed to increase estrogen's
      action on F344- or SD-derived lactotropes. The levels of basic fibroblast growth
      factor production and secretion by TGF-beta 3 and estradiol were much higher in
      F344-derived FS cells than in SD-derived FS cells. However, the lactotropes'
      growth response to basic fibroblast growth factor was similar in both strains.
      These data suggest that cell-cell interaction between FS cells and lactotropes
      regulates estradiol's mitogenic action on lactotropes and also determines
      lactotrope susceptibility to the steroid.

PMID- 14670998
TI  - Dehydroepiandrosterone metabolism by 3beta-hydroxysteroid dehydrogenase/Delta5
      Delta4 isomerase in adult zebra finch brain: sex difference and rapid effect of
      stress.
AB  - Dehydroepiandrosterone (DHEA) is a precursor to sex steroids such as
      androstenedione (AE), testosterone (T), and estrogens. DHEA has potent effects on
      brain and behavior, although the mechanisms remain unclear. One possible
      mechanism of action is that DHEA is converted within the brain to sex steroids.
      3beta-Hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase (3beta-HSD) catalyzes
      the conversion of DHEA to AE. AE can then be converted to T and estrogen within
      the brain. We test the hypothesis that 3beta-HSD is expressed in the adult brain
      in a region- and sex-specific manner using the zebra finch (Taeniopygia guttata),
      a songbird with robust sex differences in song behavior and telencephalic song
      nuclei. In zebra finch brain, DHEA is converted by 3beta-HSD to AE and
      subsequently to estrogens and 5alpha- and 5beta-reduced androgens. 3beta-HSD
      activity is highest in the diencephalon and telencephalon. In animals killed
      within 2-3 min of disturbance, baseline 3beta-HSD activity in portions of the
      telencephalon is higher in females than males. Acute restraint stress (10 min)
      decreases 3beta-HSD activity in females but not in males, and in stressed
      animals, telencephalic 3beta-HSD activity is greater in males than in females.
      Thus, the baseline sex difference is rapidly reversed by stress. To our
      knowledge, this is the first demonstration of 1) brain region differences in DHEA
      metabolism by 3beta-HSD, 2) rapid modulation of 3beta-HSD activity, and 3) sex
      differences in brain 3beta-HSD and regulation by stress. Songbirds are good
      animal models for studying the regulation and functions of DHEA and neurosteroids
      in the nervous system.

PMID- 14670999
TI  - A role for CCAAT/enhancer-binding protein beta in the basal regulation of the
      distal-less 3 gene promoter in placental cells.
AB  - The homeodomain protein Distal-less 3 (Dlx3) is essential for normal placental
      development in mice. Dlx3-null mice die by embryonic day 10.0 due to placental
      failure. The aim of our studies was to examine the transcriptional regulation and
      expression of Dlx3 in choriocarcinoma cell lines and primary trophoblasts from
      human placenta. A Dlx3 promoter fragment coupled to a luciferase reporter gene
      was sufficient to increase luciferase activity more than 11-fold over a
      luciferase control vector in choriocarcinoma cells, but not in a heterologous
      gonadotrope cell line. A 5' deletion series of the Dlx3 promoter revealed that a
      13-nucleotide CCAAT box-containing element was required for basal expression in
      choriocarcinoma cell lines. Mutation of the CCAAT box within the context of the
      full-length promoter resulted in reduced basal activation of the Dlx3 reporter
      gene, suggesting that the CCAAT box was required for full basal expression.
      Western blot analysis revealed that Dlx3, CCAAT/enhancer-binding protein alpha
      (C/EBP alpha), and C/EBP beta were present in choriocarcinoma cells and isolated
      trophoblasts from term human placentas. Electrophoretic mobility shift assays
      revealed the formation of a specific complex between choriocarcinoma cell nuclear
      extracts and the Dlx3 CCAAT box sequence. Competition and antibody
      electrophoretic mobility shift assays revealed that CCAAT/enhancer-binding
      protein beta (C/EBP beta) binds the Dlx3 CCAAT box sequence. Overexpression of
      C/EBP beta was sufficient to increase basal expression of a Dlx3 reporter gene in
      a dose-dependent manner. These studies provide the first insight into the
      mechanism(s) of Dlx3 gene expression in placental cells and suggest a role for
      C/EBP beta in the basal regulation of the Dlx3 gene.

PMID- 14671000
TI  - Regulation of cell cycle progression by calcium/calmodulin-dependent pathways.
AB  - Many hormones, growth factors, and cytokines regulate proliferation of their
      target cells. Perhaps the most universal signaling cascades required for
      proliferative responses are those initiated by transient rises in intracellular
      calcium (Ca(2+)). The major intracellular receptor for Ca(2+) is calmodulin
      (CaM). CaM is a small protein that contains four EF-hand Ca(2+) binding sites and
      is highly conserved among eukaryotes. In all organisms in which the CaM gene has
      been deleted, it is essential. Although Ca(2+)/CaM is required for proliferation
      in both unicellular and multicellular eukaryotes, the essential targets of
      Ca(2+)/CaM-dependent pathways required for cell proliferation remain elusive.
      Potential Ca(2+)/CaM-dependent targets include the serine/threonine phosphatase
      calcineurin and the family of multifunctional Ca(2+)/CaM-dependent protein
      kinases. Whereas these enzymes are essential in Aspergillus nidulans, they are
      not required under normal growth conditions in yeast. However, in mammalian
      cells, studies demonstrate that both types of enzymes contribute to the
      regulation of cell cycle progression. Unfortunately, the mechanism by which
      Ca(2+)/CaM and its downstream targets, particularly calcineurin and the
      Ca(2+)/CaM-dependent protein kinases, regulate key cell cycle-regulatory
      proteins, remains enigmatic. By understanding how Ca(2+)/CaM regulates cell cycle
      progression in normal mammalian cells, we may gain insight into how hormones
      control cell division and how cancer cells subvert the need for Ca(2+) and its
      downstream targets to proliferate.

PMID- 14671001
TI  - Epidermal homeostasis: the role of the growth hormone and insulin-like growth
      factor systems.
AB  - GH and IGF-I and -II were first identified by their endocrine activity.
      Specifically, IGF-I was found to mediate the linear growth-promoting actions of
      GH. It is now evident that these two growth factor systems also exert widespread
      activity throughout the body and that their actions are not always
      interconnected. The literature highlights the importance of the GH and IGF
      systems in normal skin homeostasis, including dermal/epidermal cross-talk. GH
      activity, sometimes mediated via IGF-I, is primarily evident in the dermis,
      particularly affecting collagen synthesis. In contrast, IGF action is an
      important feature of the dermal and epidermal compartments, predominantly
      enhancing cell proliferation, survival, and migration. The locally expressed IGF
      binding proteins play significant and complex roles, primarily via modulation of
      IGF actions. Disturbances in GH and IGF signaling pathways are implicated in the
      pathophysiology of several skin perturbations, particularly those exhibiting
      epidermal hyperplasia (e.g., psoriasis, carcinomas). Additionally, many studies
      emphasize the potential use of both growth factors in the treatment of skin
      wounds; for example, burn patients. This overview concerns the role and
      mechanisms of action of the GH and IGF systems in skin and maintenance of
      epidermal integrity in both health and disease.

PMID- 14671004
TI  - Insights into G protein structure, function, and regulation.
AB  - In multicellular organisms from Caenorhabditis elegans to Homo sapiens, the
      maintenance of homeostasis is dependent on the continual flow and processing of
      information through a complex network of cells. Moreover, in order for the
      organism to respond to an ever-changing environment, intercellular signals must
      be transduced, amplified, and ultimately converted to the appropriate
      physiological response. The resolution of the molecular events underlying signal
      response and integration forms the basis of the signal transduction field of
      research. An evolutionarily highly conserved group of molecules known as
      heterotrimeric guanine nucleotide-binding proteins (G proteins) are key
      determinants of the specificity and temporal characteristics of many signaling
      processes and are the topic of this review. Numerous hormones, neurotransmitters,
      chemokines, local mediators, and sensory stimuli exert their effects on cells by
      binding to heptahelical membrane receptors coupled to heterotrimeric G proteins.
      These highly specialized transducers can modulate the activity of multiple
      signaling pathways leading to diverse biological responses. In vivo, specific
      combinations of G alpha- and G beta gamma-subunits are likely required for
      connecting individual receptors to signaling pathways. The structural
      determinants of receptor-G protein-effector specificity are not completely
      understood and, in addition to involving interaction domains of these primary
      acting proteins, also require the participation of scaffolding and regulatory
      proteins.

PMID- 14671005
TI  - Systemic and local regulation of the growth plate.
AB  - The growth plate is the final target organ for longitudinal growth and results
      from chondrocyte proliferation and differentiation. During the first year of
      life, longitudinal growth rates are high, followed by a decade of modest
      longitudinal growth. The age at onset of puberty and the growth rate during the
      pubertal growth spurt (which occurs under the influence of estrogens and GH)
      contribute to sex difference in final height between boys and girls. At the end
      of puberty, growth plates fuse, thereby ceasing longitudinal growth. It has been
      recognized that receptors for many hormones such as estrogen, GH, and
      glucocorticoids are present in or on growth plate chondrocytes, suggesting that
      these hormones may influence processes in the growth plate directly. Moreover,
      many growth factors, i.e., IGF-I, Indian hedgehog, PTHrP, fibroblast growth
      factors, bone morphogenetic proteins, and vascular endothelial growth factor, are
      now considered as crucial regulators of chondrocyte proliferation and
      differentiation. In this review, we present an update on the present perception
      of growth plate function and the regulation of chondrocyte proliferation and
      differentiation by systemic and local regulators of which most are now related to
      human growth disorders.

PMID- 14671007
TI  - Current perspective on the pathogenesis of Graves' disease and ophthalmopathy.
AB  - Graves' disease (GD) is a very common autoimmune disorder of the thyroid in which
      stimulatory antibodies bind to the thyrotropin receptor and activate glandular
      function, resulting in hyperthyroidism. In addition, some patients with GD
      develop localized manifestations including ophthalmopathy (GO) and dermopathy.
      Since the cloning of the receptor cDNA, significant progress has been made in
      understanding the structure-function relationship of the receptor, which has been
      discussed in a number of earlier reviews. In this paper, we have focused our
      discussion on studies related to the molecular mechanisms of the disease
      pathogenesis and the development of animal models for GD. It has become apparent
      that multiple factors contribute to the etiology of GD, including host genetic as
      well as environmental factors. Studies in experimental animals indicate that GD
      is a slowly progressing disease that involves activation and recruitment of
      thyrotropin receptor-specific T and B cells. This activation eventually results
      in the production of stimulatory antibodies that can cause hyperthyroidism.
      Similarly, significant new insights have been gained in our understanding of GO
      that occurs in a subset of patients with GD. As in GD, both environmental and
      genetic factors play important roles in the development of GO. Although a number
      of putative ocular autoantigens have been identified, their role in the
      pathogenesis of GO awaits confirmation. Extensive analyses of orbital tissues
      obtained from patients with GO have provided a clearer understanding of the roles
      of T and B cells, cytokines and chemokines, and various ocular tissues including
      ocular muscles and fibroblasts. Equally impressive is the progress made in
      understanding why connective tissues of the orbit and the skin in GO are singled
      out for activation and undergo extensive remodeling. Results to date indicate
      that fibroblasts can act as sentinel cells and initiate lymphocyte recruitment
      and tissue remodeling. Moreover, these fibroblasts can be readily activated by Ig
      in the sera of patients with GD, suggesting a central role for them in the
      pathogenesis. Collectively, recent studies have led to a better understanding of
      the pathogenesis of GD and GO and have opened up potential new avenues for
      developing novel treatments for GD and GO.

PMID- 14671008
TI  - Genetically modified animals in endocrinology. Knockout mouse models for bone
      studies.

PMID- 14671009
TI  - Overexpression of selenocysteine methyltransferase in Arabidopsis and Indian
      mustard increases selenium tolerance and accumulation.
AB  - A major goal of phytoremediation is to transform fast-growing plants with genes
      from plant species that hyperaccumulate toxic trace elements. We overexpressed
      the gene encoding selenocysteine methyltransferase (SMT) from the selenium (Se)
      hyperaccumulator Astragalus bisulcatus in Arabidopsis and Indian mustard
      (Brassica juncea). SMT detoxifies selenocysteine by methylating it to
      methylselenocysteine, a nonprotein amino acid, thereby diminishing the toxic
      misincorporation of Se into protein. Our Indian mustard transgenic plants
      accumulated more Se in the form of methylselenocysteine than the wild type. SMT
      transgenic seedlings tolerated Se, particularly selenite, significantly better
      than the wild type, producing 3- to 7-fold greater biomass and 3-fold longer root
      lengths. Moreover, SMT plants had significantly increased Se accumulation and
      volatilization. This is the first study, to our knowledge, in which a fast
      growing plant was genetically engineered to overexpress a gene from a
      hyperaccumulator in order to increase phytoremediation potential.

PMID- 14671010
TI  - Histochemical analysis reveals organ-specific quantitative trait loci for enzyme
      activities in Arabidopsis.
AB  - To identify genetic loci involved in the regulation of organ-specific enzyme
      activities, a specific histochemical staining protocol was used in combination
      with quantitative trait locus (QTL) analysis. Using phosphoglucomutase (PGM) as
      an example, it is shown that enzyme activity can specifically, and with high
      resolution, be visualized in non-sectioned seedlings of Arabidopsis. The
      intensities of staining were converted to quantitative data and used as trait for
      QTL analysis using Landsberg erecta x Cape Verde Islands recombinant inbred
      lines. Independently, PGM activities were quantified in whole-seedling extracts,
      and these data were also used for QTL analysis. On the basis of extract data, six
      significant (P < 0.05) loci affecting PGM activity were found. From the
      histochemical data, one or more specific QTLs were found for each organ analyzed
      (cotyledons, shoot apex, hypocotyl, root, root neck, root tip, and root hairs).
      Loci detected for PGM activity in extracts colocated with loci for histochemical
      staining. QTLs were found coinciding with positions of (putative) PGM genes but
      also at other positions, the latter ones supposedly pointing toward regulatory
      genes. Some of this type of loci were also organ specific. It is concluded that
      QTL analysis based on histochemical data is feasible and may reveal organ
      specific loci involved in the regulation of metabolic pathways.

PMID- 14671011
TI  - Isolated durum wheat and potato cell mitochondria oxidize externally added NADH
      mostly via the malate/oxaloacetate shuttle with a rate that depends on the
      carrier-mediated transport.
AB  - We investigated whether and how mitochondria from durum wheat (Triticum durum
      Desf.) and potato (Solanum tuberosum), isolated from etiolated shoots and a cell
      suspension culture, respectively, oxidize externally added NADH via the
      mitochondrial shuttles; in particular, we compared the shuttles and the external
      NADH dehydrogenase (NADH DHExt) with respect to their capacity to oxidize
      external NADH. We found that external NADH and NADPH can be oxidized via two
      separate DHExt, whereas under conditions in which the activities of NAD(P)H DHExt
      are largely prevented, NADH (but not NADPH) is oxidized in the presence of
      external malate (MAL) and MAL dehydrogenase, in a manner sensitive to several non
      penetrant compounds according to the occurrence of the MAL/oxaloacetate (OAA)
      shuttle. In durum wheat mitochondria and potato cell mitochondria, the rate of
      NADH oxidation was limited by the rate of a novel carrier, the MAL/OAA
      antiporter, which is different from other carriers thought to transport OAA
      across the mitochondrial membrane. No NAD(P)H oxidation occurred arising from the
      MAL/Aspartate and the alpha-glycerophosphate/dihydroxyacetonphosphate shuttles.
      We determined the kinetic parameters of the enzymes and the antiporter involved
      in NADH oxidation, and, on the basis of a kinetic analysis, we showed that, at
      low physiological NADH concentrations, oxidation via the MAL/OAA shuttle occurred
      with a higher efficiency than that due to the NADH DHExt (about 100- and 10-fold
      at 1 microm NADH in durum wheat mitochondria and in potato cell mitochondria,
      respectively). The NADH DHExt contribution to NADH oxidation increased with
      increasing NADH concentration.

PMID- 14671012
TI  - Modeling nitrogen uptake in oilseed rape cv Capitol during a growth cycle using
      influx kinetics of root nitrate transport systems and field experimental data.
AB  - The use of kinetic equations of NO3- transport systems in oilseed rape (Brassica
      napus), determined by 15NO3- labeling under controlled conditions, combined with
      experimental field data from the INRA-Chalons rape database were used to model
      NO3- uptake during the plant growth cycle. The quantitative effects of different
      factors such as day/night cycle, ontogenetic stages, root temperature,
      photosynthetically active radiation, and soil nitrate availability on different
      components of the constitutive high-affinity transport systems, constitutive low
      affinity transport systems, inducible low-affinity transport systems, and
      inducible high-affinity transport systems of nitrate were then determined to
      improve the model's predictions. Simulated uptake correlated well with measured
      values of nitrogen (N) uptake under field conditions for all N fertilization
      rates tested. Model outputs showed that the high-affinity transport system
      accounted for about 89% of total NO3- uptake (18% and 71% for constitutive high
      affinity transport systems and inducible high-affinity transport systems,
      respectively) when no fertilizer was applied. The low-affinity transport system
      accounted for a minor proportion of total N uptake, and its activity was
      restricted to the early phase of the growth cycle. However, N fertilization in
      spring increased the duration of its contribution to total N uptake. Overall,
      data show that this mechanistic and environmentally regulated approach is a
      powerful means to simulate total N uptake in the field with the advantage of
      taking both physiologically regulated processes at the overall plant level and
      specific nitrate transport system characteristics into account.

PMID- 14671013
TI  - Chlamydomonas reinhardtii secretes compounds that mimic bacterial signals and
      interfere with quorum sensing regulation in bacteria.
AB  - The unicellular soil-freshwater alga Chlamydomonas reinhardtii was found to
      secrete substances that mimic the activity of the N-acyl-L-homoserine lactone
      (AHL) signal molecules used by many bacteria for quorum sensing regulation of
      gene expression. More than a dozen chemically separable but unidentified
      substances capable of specifically stimulating the LasR or CepR but not the LuxR,
      AhyR, or CviR AHL bacterial quorum sensing reporter strains were detected in
      ethyl acetate extracts of C. reinhardtii culture filtrates. Colonies of C.
      reinhardtii and Chlorella spp. stimulated quorum sensing-dependent luminescence
      in Vibrio harveyi, indicating that these algae may produce compounds that affect
      the AI-2 furanosyl borate diester-mediated quorum sensing system of Vibrio spp.
      Treatment of the soil bacterium Sinorhizobium meliloti with a partially purified
      LasR mimic from C. reinhardtii affected the accumulation of 16 of the 25 proteins
      that were altered in response to the bacterium's own AHL signals, providing
      evidence that the algal mimic affected quorum sensing-regulated functions in this
      wild-type bacterium. Peptide mass fingerprinting identified 32 proteins affected
      by the bacterium's AHLs or the purified algal mimic, including GroEL chaperonins,
      the nitrogen regulatory protein PII, and a GTP-binding protein. The algal mimic
      was able to cancel the stimulatory effects of bacterial AHLs on the accumulation
      of seven of these proteins, providing evidence that the secretion of AHL mimics
      by the alga could be effective in disruption of quorum sensing in naturally
      encountered bacteria.

PMID- 14671014
TI  - Occurrence of the primary cell wall polysaccharide rhamnogalacturonan II in
      pteridophytes, lycophytes, and bryophytes. Implications for the evolution of
      vascular plants.
AB  - Borate ester cross-linking of the cell wall pectic polysaccharide
      rhamnogalacturonan II (RG-II) is required for the growth and development of
      angiosperms and gymnosperms. Here, we report that the amounts of borate cross
      linked RG-II present in the sporophyte primary walls of members of the most
      primitive extant vascular plant groups (Lycopsida, Filicopsida, Equisetopsida,
      and Psilopsida) are comparable with the amounts of RG-II in the primary walls of
      angiosperms. By contrast, the gametophyte generation of members of the avascular
      bryophytes (Bryopsida, Hepaticopsida, and Anthocerotopsida) have primary walls
      that contain small amounts (approximately 1% of the amounts of RG-II present in
      angiosperm walls) of an RG-II-like polysaccharide. The glycosyl sequence of RG-II
      is conserved in vascular plants, but these RG-IIs are not identical because the
      non-reducing L-rhamnosyl residue present on the aceric acid-containing side chain
      of RG-II of all previously studied plants is replaced by a 3-O-methyl rhamnosyl
      residue in the RG-IIs isolated from Lycopodium tristachyum, Ceratopteris
      thalictroides, Platycerium bifurcatum, and Psilotum nudum. Our data indicate that
      the amount of RG-II incorporated into the walls of plants increased during the
      evolution of vascular plants from their bryophyte-like ancestors. Thus, the
      acquisition of a boron-dependent growth habit may be correlated with the ability
      of vascular plants to maintain upright growth and to form lignified secondary
      walls. The conserved structures of pteridophyte, lycophyte, and angiosperm RG-IIs
      suggests that the genes and proteins responsible for the biosynthesis of this
      polysaccharide appeared early in land plant evolution and that RG-II has a
      fundamental role in wall structure.

PMID- 14671015
TI  - Isolation and characterization of an RIP (ribosome-inactivating protein)-like
      protein from tobacco with dual enzymatic activity.
AB  - Ribosome-inactivating proteins (RIPs) are N-glycosidases that remove a specific
      adenine from the sarcin/ricin loop of the large rRNA, thus arresting protein
      synthesis at the translocation step. In the present study, a protein termed
      tobacco RIP (TRIP) was isolated from tobacco (Nicotiana tabacum) leaves and
      purified using ion exchange and gel filtration chromatography in combination with
      yeast ribosome depurination assays. TRIP has a molecular mass of 26 kD as
      evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and showed
      strong N-glycosidase activity as manifested by the depurination of yeast rRNA.
      Purified TRIP showed immunoreactivity with antibodies of RIPs from Mirabilis
      expansa. TRIP released fewer amounts of adenine residues from ribosomal (Artemia
      sp. and rat ribosomes) and non-ribosomal substrates (herring sperm DNA, rRNA, and
      tRNA) compared with other RIPs. TRIP inhibited translation in wheat (Triticum
      aestivum) germ more efficiently than in rabbit reticulocytes, showing an IC50 at
      30 ng in the former system. Antimicrobial assays using highly purified TRIP (50
      microg mL(-1)) conducted against various fungi and bacterial pathogens showed the
      strongest inhibitory activity against Trichoderma reesei and Pseudomonas
      solancearum. A 15-amino acid internal polypeptide sequence of TRIP was identical
      with the internal sequences of the iron-superoxide dismutase (Fe-SOD) from wild
      tobacco (Nicotiana plumbaginifolia), Arabidopsis, and potato (Solanum tuberosum).
      Purified TRIP showed SOD activity, and Escherichia coli Fe-SOD was observed to
      have RIP activity too. Thus, TRIP may be considered a dual activity enzyme
      showing RIP-like activity and Fe-SOD characteristics.

PMID- 14671016
TI  - A new abscisic acid catabolic pathway.
AB  - We report the discovery of a new hydroxylated abscisic acid (ABA) metabolite,
      found in the course of a mass spectrometric study of ABA metabolism in Brassica
      napus siliques. This metabolite reveals a previously unknown catabolic pathway
      for ABA in which the 9'-methyl group of ABA is oxidized. Analogs of (+)-ABA
      deuterated at the 8'-carbon atom and at both the 8'- and 9'-carbon atoms were fed
      to green siliques, and extracts containing the deuterated oxidized metabolites
      were analyzed to determine the position of ABA hydroxylation. The results
      indicated that hydroxylation of ABA had occurred at the 9'-methyl group, as well
      as at the 7'- and 8'-methyl groups. The chromatographic characteristics and mass
      spectral fragmentation patterns of the new ABA metabolite were compared with
      those of synthetic 9'-hydroxy ABA (9'-OH ABA), in both open and cyclized forms.
      The new compound isolated from plant extracts was identified as the cyclized form
      of 9'-OH ABA, which we have named neophaseic acid (neoPA). The proton nuclear
      magnetic resonance spectrum of pure neoPA isolated from immature seeds of B.
      napus was identical to that of the authentic synthetic compound. ABA and neoPA
      levels were high in young seeds and lower in older seeds. The open form (2Z,4E)-5
      [(1R,6S)-1-Hydroxy-6-hydroxymethyl-2,6-dimethyl-4-oxo-cyclohex-2-enyl]-3-methyl
      penta-2,4-dienoic acid, but not neoPA, exhibited ABA-like bioactivity in
      inhibiting Arabidopsis seed germination and in inducing gene expression in B.
      napus microspore-derived embryos. NeoPA was also detected in fruits of orange
      (Citrus sinensis) and tomato (Lycopersicon esculentum), in Arabidopsis, and in
      chickpea (Cicer arietinum), as well as in drought-stressed barley (Hordeum
      vulgare) and B. napus seedlings.

PMID- 14671017
TI  - Impact of unusual fatty acid synthesis on futile cycling through beta-oxidation
      and on gene expression in transgenic plants.
AB  - Arabidopsis expressing the castor bean (Ricinus communis) oleate 12-hydroxylase
      or the Crepis palaestina linoleate 12-epoxygenase in developing seeds typically
      accumulate low levels of ricinoleic acid and vernolic acid, respectively. We have
      examined the presence of a futile cycle of fatty acid degradation in developing
      seeds using the synthesis of polyhydroxyalkanoate (PHA) from the intermediates of
      the peroxisomal beta-oxidation cycle. Both the quantity and monomer composition
      of the PHA synthesized in transgenic plants expressing the 12-epoxygenase and 12
      hydroxylase in developing seeds revealed the presence of a futile cycle of
      degradation of the corresponding unusual fatty acids, indicating a limitation in
      their stable integration into lipids. The expression profile of nearly 200 genes
      involved in fatty acid biosynthesis and degradation has been analyzed through
      microarray. No significant changes in gene expression have been detected as a
      consequence of the activity of the 12-epoxygenase or the 12-hydroxylase in
      developing siliques. Similar results have also been obtained for transgenic
      plants expressing the Cuphea lanceolata caproyl-acyl carrier protein thioesterase
      and accumulating high amounts of caproic acid. Only in developing siliques of the
      tag1 mutant, deficient in the accumulation of triacylglycerols and shown to have
      a substantial futile cycling of fatty acids toward beta-oxidation, have some
      changes in gene expression been detected, notably the induction of the isocitrate
      lyase gene. These results indicate that analysis of peroxisomal PHA is a better
      indicator of the flux of fatty acid through beta-oxidation than the expression
      profile of genes involved in lipid metabolism.

PMID- 14671018
TI  - Correlation of ASN2 gene expression with ammonium metabolism in Arabidopsis.
AB  - In Arabidopsis, asparagine (Asn) synthetase is encoded by a small gene family
      (ASN1, ASN2, and ASN3). It has been shown that ASN1 and ASN2 exhibit reciprocal
      gene expression patterns toward light and metabolites. Moreover, changes in total
      free Asn levels parallel the expression of ASN1, but not ASN2. In this study, we
      show that ASN2 expression correlates with ammonium metabolism. We demonstrate
      that the light induction of ASN2 is ammonium dependent. The addition and removal
      of ammonium exerted fast and reciprocal effects on the levels of ASN2 mRNA,
      specifically under light-grown conditions. NaCl and cold stress increased
      cellular free ammonium and ASN2 mRNA levels in a coordinated manner, suggesting
      that the effects of stress on ASN2 expression may be mediated via accumulation of
      ammonium. The correlation between ASN2 and cellular ammonium metabolism was
      further demonstrated by analysis of ASN2 transgenic plants. When plants were
      grown on Murashige and Skoog medium containing 50 mm ammonium, ASN2
      overexpressors accumulated less endogenous ammonium compared with the wild-type
      Colombia-0 and ASN2 underexpressors. When plants were subjected to high-light
      irradiance, ammonium levels built up. Under such conditions, ASN2 underexpressors
      accumulated more endogenous ammonium than the wild-type Colombia-0 and ASN2
      overexpressors. These results support the notion that ASN2 is closely correlated
      to ammonium metabolism in higher plants.

PMID- 14671019
TI  - RHM2 is involved in mucilage pectin synthesis and is required for the development
      of the seed coat in Arabidopsis.
AB  - Pectins are major components of primary plant cell walls and the seed mucilage of
      Arabidopsis. Despite progress in the structural elucidation of pectins, only very
      few enzymes participating in or regulating their synthesis have been identified.
      A first candidate gene involved in the synthesis of pectinaceous
      rhamnogalacturonan I is RHM2, a putative plant ortholog to NDP-rhamnose
      biosynthetic enzymes in bacteria. Expression studies with a promoter beta
      glucuronidase construct and reverse transcription PCR data show that RHM2 is
      expressed ubiquitously. Rhm2 T-DNA insertion mutant lines were identified using a
      reverse genetics approach. Analysis of the rhm2 seeds by various staining methods
      and chemical analysis of the mucilage revealed a strong reduction of
      rhamnogalacturonan I in the mucilage and a decrease of its molecular weight. In
      addition, scanning electron microscopy of the seed surface indicated a distorted
      testa morphology, illustrating not only a structural but also a developmental
      role for RGI or rhamnose metabolism in proper testa formation.

PMID- 14671020
TI  - SETH1 and SETH2, two components of the glycosylphosphatidylinositol anchor
      biosynthetic pathway, are required for pollen germination and tube growth in
      Arabidopsis.
AB  - Glycosylphosphatidylinositol (GPI) anchoring provides an alternative to
      transmembrane domains for anchoring proteins to the cell surface in eukaryotes.
      GPI anchors are synthesized in the endoplasmic reticulum via the sequential
      addition of monosaccharides, fatty acids, and phosphoethanolamines to
      phosphatidylinositol. Deficiencies in GPI biosynthesis lead to embryonic
      lethality in animals and to conditional lethality in eukaryotic microbes by
      blocking cell growth, cell division, or morphogenesis. We report the genetic and
      phenotypic analysis of insertional mutations disrupting SETH1 and SETH2, which
      encode Arabidopsis homologs of two conserved proteins involved in the first step
      of the GPI biosynthetic pathway. seth1 and seth2 mutations specifically block
      male transmission and pollen function. This results from reduced pollen
      germination and tube growth, which are associated with abnormal callose
      deposition. This finding suggests an essential role for GPI anchor biosynthesis
      in pollen tube wall deposition or metabolism. Using transcriptomic and proteomic
      approaches, we identified 47 genes that encode potential GPI-anchored proteins
      that are expressed in pollen and demonstrated that at least 11 of these proteins
      are associated with pollen membranes by GPI anchoring. Many of the identified
      candidate proteins are homologous with proteins involved in cell wall synthesis
      and remodeling or intercellular signaling and adhesion, and they likely play
      important roles in the establishment and maintenance of polarized pollen tube
      growth.

PMID- 14671021
TI  - Dissection of Arabidopsis Bax inhibitor-1 suppressing Bax-, hydrogen peroxide-,
      and salicylic acid-induced cell death.
AB  - Overexpression of plant Bax Inhibitor-1 (BI-1) was able to suppress Bax-mediated
      cell death in yeast and Arabidopsis. Here, we demonstrate that reactive oxygen
      species production induced by the ectopic expression of Bax was insensitive to
      the coexpression of AtBI-1. Similarly, H2O2- or salicylic acid-mediated cell
      death also was suppressed in tobacco BY-2 cells overexpressing AtBI-1. To define
      the functional domain of AtBI-1 as a cell death suppressor, a truncated series of
      the AtBI-1 protein was analyzed in yeast possessing a galactose-inducible
      mammalian Bax. The results showed that DeltaC-AtBI-1 (with the C-terminal 14
      amino acids deleted) lost the ability to sustain cell growth. Furthermore, a
      mutant protein in which the C-terminal seven amino acid residues of AtBI-1 were
      replaced with others lacking a coiled-coil structure failed to inhibit cell
      death, suggesting that the C-terminal region is essential for the inhibition of
      cell death. We also noted that the C-terminal hydrophilic region was
      interchangeable between animal and plant Bax inhibitors.

PMID- 14671022
TI  - Experimental analysis of the Arabidopsis mitochondrial proteome highlights
      signaling and regulatory components, provides assessment of targeting prediction
      programs, and indicates plant-specific mitochondrial proteins.
AB  - A novel insight into Arabidopsis mitochondrial function was revealed from a large
      experimental proteome derived by liquid chromatography-tandem mass spectrometry.
      Within the experimental set of 416 identified proteins, a significant number of
      low-abundance proteins involved in DNA synthesis, transcriptional regulation,
      protein complex assembly, and cellular signaling were discovered. Nearly 20% of
      the experimentally identified proteins are of unknown function, suggesting a
      wealth of undiscovered mitochondrial functions in plants. Only approximately half
      of the experimental set is predicted to be mitochondrial by targeting prediction
      programs, allowing an assessment of the benefits and limitations of these
      programs in determining plant mitochondrial proteomes. Maps of putative orthology
      networks between yeast, human, and Arabidopsis mitochondrial proteomes and the
      Rickettsia prowazekii proteome provide detailed insights into the divergence of
      the plant mitochondrial proteome from those of other eukaryotes. These show a
      clear set of putative cross-species orthologs in the core metabolic functions of
      mitochondria, whereas considerable diversity exists in many signaling and
      regulatory functions.

PMID- 14671023
TI  - Overexpression of an Arabidopsis formin stimulates supernumerary actin cable
      formation from pollen tube cell membrane.
AB  - Formins, actin-nucleating proteins that stimulate the de novo polymerization of
      actin filaments, are important for diverse cellular and developmental processes,
      especially those dependent on polarity establishment. A subset of plant formins,
      referred to as group I, is distinct from formins from other species in having
      evolved a unique N-terminal structure with a signal peptide, a Pro-rich,
      potentially glycosylated extracellular domain, and a transmembrane domain. We
      show here that overexpression of the Arabidopsis formin AFH1 in pollen tubes
      induces the formation of arrays of actin cables that project into the cytoplasm
      from the cell membrane and that its N-terminal structure targets AFH1 to the cell
      membrane. Pollen tube elongation is a polar cell growth process dependent on an
      active and tightly regulated actin cytoskeleton. Slight increases in AFH1
      stimulate growth, but its overexpression induces tube broadening, growth
      depolarization, and growth arrest in transformed pollen tubes. These results
      suggest that AFH1-regulated actin polymerization is important for the polar
      pollen cell growth process. Moreover, severe membrane deformation was observed in
      the apical region of tip-expanded, AFH1-overexpressing pollen tubes in which an
      abundance of AFH1-induced membrane-associated actin cables was evident. These
      observations suggest that regulated AFH1 activity at the cell surface is
      important for maintaining tip-focused cell membrane expansion for the polar
      extension of pollen tubes. The cell surface-located group-I formins may play the
      integrin-analogous role as mediators of external stimuli to the actin
      cytoskeleton, and AFH1 could be important for mediating extracellular signals
      from female tissues to elicit the proper pollen tube growth response during
      pollination.

PMID- 14671024
TI  - Interactions between plasma membrane aquaporins modulate their water channel
      activity.
AB  - Plant plasma membrane intrinsic proteins (PIPs) cluster in two evolutionary
      subgroups, PIP1 and PIP2, with different aquaporin activities when expressed in
      Xenopus oocytes. Maize ZmPIP1;1 and ZmPIP1;2 do not increase the osmotic water
      permeability coefficient (Pf), whereas ZmPIP2;1, ZmPIP2;4, and ZmPIP2;5 do. Here,
      we show that coexpression of the nonfunctional ZmPIP1;2 and the functional
      ZmPIP2;1, ZmPIP2;4, or ZmPIP2;5 resulted in an increase in Pf that was dependent
      on the amount of injected ZmPIP1;2 complementary RNA. Confocal analysis of
      oocytes expressing ZmPIP1;2-green fluorescent protein (GFP) alone or ZmPIP1;2-GFP
      plus ZmPIP2;5 showed that the amount of ZmPIP1;2-GFP present in the plasma
      membrane was significantly greater in coexpressing cells. Nickel affinity
      chromatography purification of ZmPIP2;1 fused to a His tag coeluted with ZmPIP1;2
      GFP demonstrated physical interaction and heteromerization of both isoforms.
      Interestingly, coexpression of ZmPIP1;1 and ZmPIP2;5 did not result in a greater
      increase in Pf than did the expression of ZmPIP2;5 alone, but coexpression of the
      ZmPIP1;1 and ZmPIP1;2 isoforms induced a Pf increase, indicating that PIP1
      isoform heteromerization is required for both of them to act as functional water
      channels. Mutational analysis demonstrated the important role of the C-terminal
      part of loop E in PIP interaction and water channel activity induction. This
      study has revealed a new mechanism of plant aquaporin regulation that might be
      important in plant water relations.

PMID- 14671026
TI  - In vivo analysis of cell division, cell growth, and differentiation at the shoot
      apical meristem in Arabidopsis.
AB  - The aerial parts of the plant are generated by groups of rapidly dividing cells
      called shoot apical meristems. To analyze cell behavior in these structures, we
      developed a technique to visualize living shoot apical meristems using the
      confocal microscope. This method, combined with green fluorescent protein marker
      lines and vital stains, allows us to follow the dynamics of cell proliferation,
      cell expansion, and cell differentiation at the shoot apex. Using this approach,
      the effects of several mitotic drugs on meristem development were studied.
      Oryzalin (depolymerizing microtubules) very rapidly caused cell division arrest.
      Nevertheless, both cell expansion and cell differentiation proceeded in the
      treated meristems. Interestingly, DNA synthesis was not blocked, and the
      meristematic cells went through several rounds of endoreduplication in the
      presence of the drug. We next treated the meristems with two inhibitors of DNA
      synthesis, aphidicolin and hydroxyurea. In this case, cell growth and, later,
      cell differentiation were inhibited, suggesting an important role for DNA
      synthesis in growth and patterning.

PMID- 14671027
TI  - What is the role of albumin in proteinuric glomerulopathies?

PMID- 14671028
TI  - Lipid management in the proteinuric patient: do not overlook the importance of
      proteinuria reduction.

PMID- 14671029
TI  - The changing profile of acute tubulointerstitial nephritis.

PMID- 14671030
TI  - Alcohol and red wine: impact on cardiovascular risk.

PMID- 14671031
TI  - Antihypertensive treatment with calcium channel blockers: pharmacological
      pornography or useful intervention?

PMID- 14671032
TI  - Erythropoietin: is it more than correcting anaemia?

PMID- 14671025
TI  - A unique set of 11,008 onion expressed sequence tags reveals expressed sequence
      and genomic differences between the monocot orders Asparagales and Poales.
AB  - Enormous genomic resources have been developed for plants in the monocot order
      Poales; however, it is not clear how representative the Poales are for the
      monocots as a whole. The Asparagales are a monophyletic order sister to the
      lineage carrying the Poales and possess economically important plants such as
      asparagus, garlic, and onion. To assess the genomic differences between the
      Asparagales and Poales, we generated 11,008 unique ESTs from a normalized cDNA
      library of onion. Sequence analyses of these ESTs revealed microsatellite
      markers, single nucleotide polymorphisms, and homologs of transposable elements.
      Mean nucleotide similarity between rice and the Asparagales was 78% across coding
      regions. Expressed sequence and genomic comparisons revealed strong differences
      between the Asparagales and Poales for codon usage and mean GC content, GC
      distribution, and relative GC content at each codon position, indicating that
      genomic characteristics are not uniform across the monocots. The Asparagales were
      more similar to eudicots than to the Poales for these genomic characteristics.

PMID- 14671033
TI  - Cardiovascular risk in patients with renal disease: treating the risk or treating
      the risk factor?

PMID- 14671034
TI  - Flowing time on the peritoneal membrane.

PMID- 14671035
TI  - Rights of chronic renal failure patients undergoing chronic dialysis therapy.
AB  - The Patient Advocacy Committee of the International Federation of Kidney
      Foundations (IFKF) has developed a document proposing a set of rights for
      individuals with end stage renal failure (ESRF). These rights have been approved
      by the Board of Directors of the IFKF. Twenty rights have been developed and are
      organized into the following categories: (i) need of treatment and choice of
      patients; (ii) treatment of ESRF by haemodialysis; (iii) treatment of ESRF by
      peritoneal dialysis; and (iv) renal transplantation. It is the hope of this
      Committee and the IFKF that this document will provide a stimulus to more
      scientific inquiry and discussion as to what rights do patients possess with
      regard to treatment of chronic kidney disease, regardless of where they live or
      what may be their economic, social, ethnic or political status.

PMID- 14671036
TI  - Diagnostic and therapeutic strategies in hyperoxaluria: a plea for early
      intervention.

PMID- 14671037
TI  - WCN 2003 satellite symposium on kidney transplantation in the elderly, Weimar,
      Germany, June 12-14, 2003.

PMID- 14671038
TI  - Effects of mycophenolic acid on IL-6 expression of human renal proximal and
      distal tubular cells in vitro.
AB  - BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine which regulates
      immune responses and host defence mechanisms. IL-6 has been found to be increased
      in certain inflammatory conditions of the kidney, in which tubular epithelial
      cells play a pivotal role. Human renal tubular cells express IL-6. Until now no
      data about the effect of the immunosuppressant drug mycophenolic acid (MPA) on IL
      6 expression were available. METHODS: Proximal and distal tubular epithelial
      cells (PTC/DTC) have been isolated immunomagnetically. Confluent monolayers were
      stimulated with interleukin-1beta (IL-1beta; 25 U/ml), IL-1beta+ MPA (0.25-50
      micro M) or MPA alone for 48 h. Release of IL-6 protein into the supernatant was
      evaluated with an enzyme immunoassay, IL-6 mRNA expression was evaluated using
      the Quantikine mRNA kit. RESULTS: After IL-1beta stimulation, a highly
      significant 2.6- (PTC) and 3.8-fold (DTC) upregulation of IL-6 expression was
      detectable. IL-6 mRNA was upregulated by IL-1beta [1.57- (PTC) and 2.03-fold
      (DTC)]. MPA inhibited this cytokine-induced IL-6 expression in a dose-dependent
      manner. Incubation with the lowest MPA concentration had no effect on the
      stimulated upregulation, whereas all higher doses significantly decreased IL-6
      expression. Dexamethasone significantly inhibited the cytokine-induced IL-6
      protein release in PTC, but not in DTC. CONCLUSIONS: In this study we
      demonstrated for the first time an inhibitory effect of MPA on the stimulated IL
      6 expression of renal tubular epithelial cells. In contrast to older data, which
      showed a synergistic upregulation of the expression of a CC-chemokine by a
      combination of cytokines and MPA, in the present study we could demonstrate an
      immunosuppressive effect of MPA on the expression of an important cytokine.

PMID- 14671039
TI  - Amadori-configurated albumin induces nitric oxide-dependent apoptosis of
      endothelial cells: a possible mechanism of diabetic vasculopathy.
AB  - BACKGROUND: We have demonstrated previously that Amadori-configurated glycated
      albumin (GA) enhances nitric oxide synthase (NOS) activity, and this action may
      modulate glomerular hyperfiltration in early phases of diabetic nephropathy.
      Since the late stage of diabetic vasculopathy is characterized by reductions in
      viable cells within an expanded and disorganized matrix, we tested the hypothesis
      that GA enhances endothelial cell (EC) apoptosis. METHODS: Murine (t End.1) or
      human umbilical vein ECs (HUVECs) were incubated with graded GA concentrations
      (furosine 0.48-96 nmol/ml) at levels that approximated those reported in sera of
      diabetic patients (76 +/- 0.02 nmol/ml). Apoptosis was evaluated using terminal
      uridine nick end labelling (TUNEL) to detect DNA fragmentation in gel
      electrophoresis and p53 expression in immunoperoxidase. Transcription of the
      inducible (i) and constitutive (c) isoforms of NOS was detected by northern
      analysis, and total NOS activity was measured as [(3)H]citrulline production from
      [(3)H]arginine. Cells were also incubated with the NOS inhibitors L
      nitromethylarginine (L-NAME) at 0.01 M and aminoguanidine (AMG) at 0.01 M, the
      protein synthesis inhibitor cycloheximide (CHX) at 1 micro g/ml, and the NO donor
      sodium nitroprusside (SNP) at 0.01 M. RESULTS: ECs cultured in the presence of GA
      at furosine concentrations corresponding to levels in diabetic patients showed a
      significant enhancement of apoptosis. GA also caused parallel dose-dependent
      increases in iNOS mRNA expression and total NOS activity. The pro-apoptotic
      effect of GA was inhibited by L-NAME, AMG and CHX, but enhanced by SNP.
      CONCLUSIONS: We found that Amadori-configurated GA at furosine concentrations
      similar to those in diabetic patients favoured EC apoptosis through enhancement
      of iNOS activity. We propose that this process may be involved in the progressive
      cellular loss occurring in vascular and glomerular diabetic sclerosis.

PMID- 14671040
TI  - Re-endothelialization of punctured ePTFE graft: an in vitro study under pulsed
      perfusion conditions.
AB  - BACKGROUND: When used as arteriovenous (AV) shunts for haemodialysis, small
      diameter expanded polytetrafluoroethylene (ePTFE) grafts have a high failure rate
      in vivo. Attempts to improve graft patency are various, and focus on either
      improvement of implantation techniques or graft tissue engineering. The tissue
      engineering approach attempts to reproduce in grafts the properties of pristine
      vasculature. As shown in previous experiments, it is possible to grow on ePTFE
      grafts under shear stress in vitro an autologous endothelial cell layer, which
      will withstand physiological stress under in vivo conditions of blood flow. The
      aim of this study was to investigate in an in vitro model the regenerative
      potency of a tissue-engineered prosthetic vascular graft after repeated
      cannulation with a haemodialysis cannula. METHODS: Pig endothelial cells were
      harvested from an external jugular vein. Following processing of the endothelial
      cells, seven ePTFE grafts were coated with an inner cell layer and were kept
      under pulsed perfusion. Each graft was then cannulated three times with a
      standard shunt needle. The endothelium was then left to regenerate for a maximum
      of 48 h. The grafts were stained with haematoxylin/eosin before histological
      study. RESULTS: All grafts were endothelialized over the puncture sites within 48
      h. Histological analysis revealed a confluent endothelial cell lining at each
      puncture site. Cell morphology and cell pattern over puncture sites were not
      different from randomly picked locations over the graft lumen. CONCLUSION: Our
      results underline the potential of endothelial tissue engineering in vascular
      shunt surgery. Vascular bio-hybrids that have the properties of pristine vascular
      endothelium may be a key step forward in maintaining angio-access in patients who
      require haemodialysis.

PMID- 14671041
TI  - Removal of uraemic plasma factor(s) using different dialysis modalities reduces
      phosphatidylserine exposure in red blood cells.
AB  - BACKGROUND: Solute(s) retained during uraemia cause increased exposure of
      aminophospholipid phosphatidylserine (PS) on the outer surface of erythrocyte
      membranes, and this phenomenon may be involved in the pathophysiology of uraemia
      by promoting abnormal erythrocyte interactions. METHODS: We examined in a
      prospective randomized cross-over fashion the ability of various dialysis
      modalities to remove the circulating uraemic factor(s) causing increased PS
      externalization in red cells. Each patient was treated with haemodialysis (HD)
      and with on-line haemodiafiltration (HDF) using standard high-flux polysulphone
      membranes or with the new polisulphone-based Helixone membrane to compare the
      effects of dialysis technique and membrane type on PS exposure. Removal of PS was
      assessed indirectly by measuring PS-expressing normal erythrocytes exposed to
      uraemic plasma or to ultrafiltrate obtained at various time points during the
      extracorporeal session. RESULTS: Removal of the uraemic plasma factor(s) causing
      PS exposure was demonstrated by the reduced ability of uraemic plasma at the end
      of dialysis to induce PS exposure in normal erythrocytes, and by the capacity of
      ultrafiltrate from the dialysate side of the dialyzer membrane to markedly
      increase PS-positive red cells. However, the degree of removal varied according
      to the dialyzer type and to dialysis technique. Removal was greater for on-line
      HDF using the Helixone membrane, intermediate and comparable with HD with
      Helixone and with on-line HDF using standard polysulphone, and lower for HD using
      polysulphone membrane. The putative uraemic compound causing PS exposure seems to
      be highly lipophilic, somehow associated with plasma proteins, and apparently
      having a molecular weight between 10 and 10.8 kDa. CONCLUSIONS: Uraemia is
      associated with retention of compound(s) that are lipophilic, possibly protein
      bound and which cause an abnormal exposure of PS in erythrocytes. Our findings,
      that such compound(s) can be removed during dialysis and at higher rates with
      convection techniques, indicate a potential benefit for uraemic patients. The
      present results also seem to confirm the marked ability of high-flux Helixone
      membranes to eliminate high molecular weight solutes.

PMID- 14671042
TI  - Hypochlorous acid and low serum paraoxonase activity in haemodialysis patients:
      an in vitro study.
AB  - BACKGROUND: Serum paraoxonase 1 (PON1) is an oxidant-sensitive enzyme associated
      with high-density lipoprotein (HDL) that inhibits the atherogenic oxidation of
      low-density lipoprotein (LDL). In haemodialysis patients, production of reactive
      oxygen species, such as hypochlorous acid (HOCl) and hydrogen peroxide, is
      increased and serum PON1 arylesterase is abnormally low. We have examined the
      effect of HOCl and the uraemic milieu on serum PON1 arylesterase activity and the
      ability of HDL to inhibit LDL oxidation in vitro. METHODS: Serum was incubated
      with HOCl, hydrogen peroxide and products of HOCl reaction with excess cysteine,
      lysine and taurine and then serum PON1 arylesterase and serum protein tryptophan
      fluorescence were measured. The ability of plasma HDL fractions isolated by a
      dextran-sulphate method, to protect LDL from mild oxidation in air, was
      determined by a fluorimetric method using oxidation of 2,7-dichlorofluorescein
      (DCFH). RESULTS: Incubation of healthy serum with HOCl in the range 6.5-32.9
      mmol/l resulted in a linear decrease in serum PON1 arylesterase activity to 40%
      of that without HOCl and a parallel decrease in protein tryptophan fluorescence.
      The HOCl-induced decrease in serum PON1 activity was completely removed by
      reaction of HOCl with a 2.7-fold excess of alpha-amino acids but not taurine. In
      serum incubated for 1 week, the decrease in serum PON1 activity was significantly
      (P = 0.04) less while the increase in protein fluorescent advanced glycation end
      products was significantly larger (P = 0.01) in haemodialysis patients compared
      with healthy subjects. The mean decrease in mild oxidation of LDL was not
      significantly different on addition of HDL-rich fractions from haemodialysis
      patients (100 +/- 6%, n = 7) and healthy subjects (95 +/- 6%, n = 7) or on
      addition of the HDL-rich fraction from plasma treated with 0.95 mmol/l HOCl (95%)
      and control HDL (96%). The fraction rich in HDL and other high molecular weight
      compounds from plasma that had been incubated with increasing HOCl concentrations
      up to 1.9 mmol/l significantly (P = 0.001) increased (471%) the oxidation of
      DCFH. CONCLUSIONS: These results suggest that high concentrations of HOCl that
      severely oxidize serum proteins and tryptophan residues in the active site of
      PON1 are required to decrease PON1 arylesterase activity in serum. In
      haemodialysis patients, overproduction of HOCl that leads to high concentrations
      of severely oxidized proteins and increased oxidants in plasma might also
      contribute to low serum PON1 arylesterase activity, but does not appear to impair
      the ability of an HDL molecule to protect LDL from mild oxidation.

PMID- 14671043
TI  - Relative roles of endothelin-1 and angiotensin II in experimental post-ischaemic
      acute renal failure.
AB  - BACKGROUND: The relative roles of endothelin (ET)-1 and angiotensin (ANG) II in
      post-ischaemic acute renal failure (ARF) have not been fully established so far.
      With the aim of contributing to this goal, we assessed in this study the effect
      of ANG II and ET-1 blockade on the course of post-ischaemic-ARF. METHODS:
      Anaesthetized Wistar rats received i.v. either bosentan (a dual ET receptor
      antagonist; 10 mg/kg body weight) or losartan [ANG II type 1 (AT(1)) receptor
      antagonist; 5 or 10 mg/kg body weight] or both, 20 min before, during and 20 min
      after ischaemia. Rats in the control group received the vehicle via the same
      route. Survival and renal function were monitored up to 8 days after the
      ischaemic challenge, while haemodynamic parameters were measured 24 h after ARF.
      RESULTS: Our results demonstrate that bosentan treatment has a more beneficial
      effect on experimental ARF than losartan. The survival rate was remarkably higher
      in bosentan-treated rats than in both rat groups treated with losartan. In the
      ARF group treated with bosentan, renal blood flow (RBF) was increased by 129% in
      comparison with the untreated ARF group, whereas in the losartan-treated ARF
      groups, RBF was only approximately 35 or 38% higher than in control ARF rats. The
      glomerular filtration rate was markedly higher in bosentan-treated rats than in
      all other ARF groups on the first and second day after ischaemia. Tubular cell
      injury was less severe in bosentan-treated rats than in the control ARF rats, but
      in losartan-treated groups it was similar to that in the ARF group. Concurrent
      blockade of both ET and AT(1) receptors did not improve ARF because this
      treatment induced a marked decrease in blood pressure. CONCLUSIONS: These results
      suggest that ET-1 blockade is more efficient in improving the early course of
      post-ischaemic renal injury than ANG II inhibition, and that blockade of ET-1
      might be effective in prophylaxis of ischaemic ARF.

PMID- 14671044
TI  - Quality of sleep in patients with chronic kidney disease.
AB  - BACKGROUND: Sleep disorders are common in patients with renal failure on
      dialysis; however, the prevalence of "poor sleep" in patients with chronic kidney
      disease (CKD) not yet on dialysis is not known. This study aimed to measure the
      prevalence of "poor sleep" in CKD patients and to examine the association between
      quality of sleep and the degree of renal impairment in this population. METHODS:
      Quality of sleep was measured using the Pittsburgh Sleep Quality Index (PSQI) in
      120 prevalent CKD patients. RESULTS: Sixty-three subjects (53%) had "poor sleep"
      defined as a global PSQI score >5. There was no statistically significant
      relationship between the global PSQI score and the blood urea nitrogen level
      (BUN), serum creatinine level or calculated creatinine clearance, but the sleep
      efficiency component score correlated with BUN (r = 0.19, P = 0.04) and serum
      creatinine (r = 0.20, P = 0.03). A history of depression was the only independent
      predictor of "poor sleep" (global PSQI >5). CONCLUSIONS: "Poor sleep" is common
      in CKD patients. Quality of sleep decreases in the early stages of CKD and does
      not appear to be associated with the subsequent degree of renal failure. Large
      prospective longitudinal studies of quality of sleep in CKD patients are needed
      to confirm the high prevalence of impaired quality of sleep in this population
      and examine the association between renal function and quality of sleep while
      controlling for potential confounding variables.

PMID- 14671045
TI  - Haemodialysis prescription, adherence and nutritional indicators in five European
      countries: results from the Dialysis Outcomes and Practice Patterns Study
      (DOPPS).
AB  - BACKGROUND: The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a
      prospective, observational study designed to evaluate practice patterns in random
      samples of haemodialysis facilities and patients across three continents.
      Participating countries include France, Germany, Italy, Spain and the UK (Euro
      DOPPS), Japan and the USA. DOPPS data collection has used the same questionnaires
      and protocols across all participating countries to assess components of dialysis
      therapy and outcomes. This study focuses on dialysis prescription, adherence and
      nutrition among the Euro-DOPPS countries. METHODS: In each Euro-DOPPS country,
      patients were selected randomly from 20-21 representative facilities. Simple
      means and frequencies were calculated to compare relevant data elements to gain
      insights into differences in therapeutic aspects among nationally representative
      patients. Participants entering the study within 90 days of beginning dialysis
      therapy were excluded from these analyses. RESULTS: Among the five countries,
      mean delivered dose as measured by normalized urea clearance (Kt/V) varied from
      1.28 to 1.50 and was accompanied by differences in dialysis prescription
      components, including blood flow rates, treatment times, and dialyser membrane
      and flux characteristics. By country, a nearly 2-fold difference was observed in
      indicators of patient adherence and management (skipping and shortening dialysis,
      hyperkalaemia, hyperphosphataemia and high interdialytic weight gain). Indicators
      of malnutrition varied substantially. CONCLUSIONS: This study demonstrates
      differences in the management of haemodialysis patients across Euro-DOPPS and
      offers opportunities for improving dialysis dose, adherence and nutrition.
      Correlation of differences in practice patterns at the dialysis unit level with
      patient outcomes will offer new insights into improving dialysis therapy.

PMID- 14671046
TI  - Mortality and hospitalization in haemodialysis patients in five European
      countries: results from the Dialysis Outcomes and Practice Patterns Study
      (DOPPS).
AB  - BACKGROUND: Mortality and hospitalization rates are reported for nationally
      representative random samples of haemodialysis patients treated at randomly
      selected dialysis facilities in five European countries participating in the
      Dialysis Outcomes and Practice Pattern Study (DOPPS) (France, Germany, Italy,
      Spain and the UK). RESULTS: In the UK, 28.1% of haemodialysis patients received
      prior peritoneal dialysis treatment compared with 4.2-8.3% in other countries.
      Kidney transplantation rates ranged from 3.3 (per 100 patient years) in Italy to
      11.6 in Spain. The relative risk (RR) of mortality, adjusted for age, sex and
      diabetes status was significantly higher in the UK (RR = 1.39, P = 0.02) compared
      with Italy (reference) and increased in association with age (RR = 1.60 for every
      10 years older, P <0.001), diabetes as cause of end-stage renal disease (ESRD)
      (RR = 1.55, P < 0.001), male patients <65 years (RR = 1.29, P = 0.02) and
      peritoneal dialysis in the 12 months prior to starting haemodialysis (RR = 1.72,
      P = 0.06). Hospitalization for cardiovascular disease was highest in France and
      Germany (0.40 and 0.43 hospitalizations per patient year, respectively) and
      lowest in the UK (0.19), although cardiovascular comorbidity was similar in the
      UK and France. Hospitalization rates for vascular access-related infection ranged
      from 0.01 hospitalizations per patient year in Italy to 0.08 in the UK,
      consistent with the higher dialysis catheter use in the UK (25%) vs Italy (5%).
      Hospitalization risk was significantly higher in France than in other Euro-DOPPS
      countries and was significantly (P < 0.05) associated with prior peritoneal
      dialysis therapy, peripheral vascular disease, gastrointestinal bleeding in the
      prior 12 months, diabetes, cancer, cardiac disease, psychiatric disease and
      recent onset of ESRD (within 30 days of study entry). CONCLUSIONS: The large
      differences in haemodialysis practice and outcomes in the Euro-DOPPS countries
      suggest opportunities for improvement in patient care.

PMID- 14671047
TI  - Anaemia in haemodialysis patients of five European countries: association with
      morbidity and mortality in the Dialysis Outcomes and Practice Patterns Study
      (DOPPS).
AB  - BACKGROUND: The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a
      prospective, observational study based on data collected from nationally
      representative samples of haemodialysis facilities. The burden of anaemia in
      haemodialysis patients is substantial, leading to considerable morbidity,
      mortality and reduced quality of life. This study examines anaemia management and
      outcomes based on data from five European countries participating in the DOPPS:
      France, Germany, Italy, Spain and the UK. METHODS: Baseline data on demographics,
      co-morbidities and anaemia management in 4591 haemodialysis patients from 101
      nephrology facilities were collected in 1998-2000. Using multivariate Cox
      survival analyses to adjust for patient characteristics, relationships between
      haemoglobin concentration at study entry and rates of mortality and
      hospitalization were evaluated. RESULTS: For a year 2000 sample of prevalent
      patients on haemodialysis >180 days, mean haemoglobin concentration was 11.0
      g/dl; 53% had a haemoglobin concentration > or = 11 g/dl [1998-1999 = 44% (P <
      0.05)]. In 2000, 84% of prevalent patients were prescribed recombinant human
      erythropoietin (rHuEpo). Higher haemoglobin concentrations were associated with
      decreased relative risk (RR) for mortality (RR = 0.95 for every 1 g/dl higher
      haemoglobin, P = 0.03) and hospitalization (RR = 0.96, P = 0.02). Patients with
      haemoglobin <10 g/dl were 29% more likely to be hospitalized than patients with
      haemoglobin 11-12 g/dl (P < 0.001). CONCLUSION: Even after adjustment, lower
      haemoglobin concentrations were associated with higher morbidity and mortality in
      European haemodialysis patients. A trend to increased haemoglobin concentrations
      was observed following publication of the European Best Practice Guidelines
      (EBPG) on anaemia management for chronic kidney disease patients, but efforts
      must continue to achieve EBPG goals.

PMID- 14671048
TI  - Cholecystokinin and leptin: their influence upon the eating behaviour and
      nutrient intake of dialysis patients.
AB  - BACKGROUND: We have used serial visual analogue scores to demonstrate
      disturbances of the appetite profile in dialysis patients. This is potentially
      important as dialysis patients are prone to malnutrition yet have a lower
      nutrient intake than controls. Appetite disturbance may be influenced by
      accumulation of appetite inhibitors such as leptin and cholecystokinin (CCK) in
      dialysis patients. METHODS: Fasting blood samples were drawn from 43 controls, 50
      haemodialysis (HD) and 39 peritoneal dialysis (PD) patients to measure leptin and
      CCK. Hunger and fullness scores were derived from profiles compiled using hourly
      visual analogue scores. Nutrient intake was derived from 3 day dietary records.
      RESULTS: Fasting CCK was elevated for PD (6.73 +/- 4.42 ng/l vs control 4.99 +/-
      2.23 ng/l, P < 0.05; vs HD 4.43 +/- 2.15 ng/l, P < 0.01). Fasting CCK correlated
      with the variability of the hunger (r = 0.426, P = 0.01) and fullness (r = 0.52,
      P = 0.002) scores for PD. There was a notable relationship with the increase in
      fullness after lunch for PD (r = 0.455, P = 0.006). When well nourished PD
      patients were compared with their malnourished counterparts, CCK was higher in
      the malnourished group (P = 0.004). Leptin levels were higher for the dialysis
      patients than controls (HD and PD, P < 0.001) with pronounced hyperleptinaemia
      evident in some PD patients. Control leptin levels demonstrated correlation with
      fullness scores (e.g. peak fullness, r = 0.45, P = 0.007) but the dialysis
      patients did not. PD nutrient intake (energy and protein intake, r = -0.56, P <
      0.0001) demonstrated significant negative correlation with leptin. CONCLUSION:
      Increased CCK levels appear to influence fullness and hunger perception in PD
      patients and thus may contribute to malnutrition. Leptin does not appear to
      affect perceived appetite in dialysis patients but it may influence nutrient
      intake in PD patients via central feeding centres.

PMID- 14671049
TI  - Association between serum ferritin and measures of inflammation, nutrition and
      iron in haemodialysis patients.
AB  - BACKGROUND: Serum ferritin is a frequently used marker of iron status in dialysis
      patients. Iron administration is to be withheld for ferritin values >800 ng/ml
      according to K/DOQI guidelines. We hypothesized that such non-iron-related
      factors as elements of the malnutrition-inflammation complex syndrome (MICS) may
      increase serum ferritin concentration independently of iron status. METHODS: We
      studied 82 prevalent maintenance haemodialysis (MHD) patients (including 43 men),
      aged 55.7 +/- 15.3 years. The inflammatory and nutritional status was evaluated
      by serum C-reactive protein (CRP), Subjective Global Assessment (SGA) and its
      newer, fully quantitative versions, i.e. Dialysis Malnutrition Score (DMS) and
      Malnutrition-Inflammation Score (MIS). RESULTS: All but six patients had been on
      maintenance doses of intravenous iron dextran (between 100 and 200 mg/month)
      during the 10 weeks prior to the measurements. Serum ferritin levels were
      increased across SGA categories: (ANOVA P-value 0.03). Both unadjusted and
      multivariate adjusted correlation coefficients (r) for serum ferritin and CRP vs
      pertinent values were statistically significant for DMS and MIS and some other
      measures of nutritional status and iron indices. After deleting 10 MHD patients
      with either iron deficiency (ferritin <200 ng/ml) or iron overload (ferritin
      >2000 ng/ml), in the remaining 72 MHD patients both bivariate and multivariate
      correlations were much stronger and statistically significant (r = -0.33 and 
      0.29, respectively, P < 0.01). A multivariate model showed simultaneous,
      significant correlations between serum ferritin and both markers of inflammation
      and iron status independent of each other. After dividing the 72 MHD patients
      into two groups of serum ferritin based on a K/DOQI recommended serum ferritin
      cut-off of 800 ng/ml, the MIS and logarithm of serum CRP were significantly
      higher in the higher ferritin group. CONCLUSIONS: Serum ferritin values in the
      range of 200-2000 ng/ml may be increased due to non-iron-related factors
      including elements of MICS.

PMID- 14671050
TI  - The variability and accurate assessment of microinflammation in haemodialysis
      patients.
AB  - BACKGROUND: Systemic microinflammation is correlated with atherosclerosis. It
      needs a reliable assessment. This study explores the temporal variations of three
      inflammatory indexes [C-reactive protein (CRP), serum amyloid A (SAA) and
      interleukin-6 (IL-6)] in a period free of clinical events and tests the
      reliability of their multiple measurements for the assessment of
      microinflammation in haemodialysis (HD) patients, a population at high risk of
      atherosclerotic cardiovascular disease. METHODS: For 4 months, serum CRP, SAA and
      IL-6 were measured in 29 HD patients during the weeks they were free of
      inflammatory clinical events (> or =12 measurements for each index in every
      patient). The components of the variance as well as the reliability of two to
      five measurements for each index, aimed at assessing microinflammation precisely,
      were computed. RESULTS: The median (interquartile range) of CRP was 2.3 (0.9-4.9)
      mg/l, of SAA 3.7 (2.1-9.3) mg/l and of IL-6 4.4 (2.2-7.7) pg/ml. Patients were
      approximately equally distributed between three groups of low, intermediate and
      high variability for each index. The contribution of intraindividual (biological)
      variation to the total of variance was 71.3%, 69.3% and 86.7% for CRP, SAA and IL
      6, respectively (higher than in all other similar studies in healthy
      populations). Using two measurements, the estimated reliability was 57-68% for
      CRP in two-thirds of the patients (comparable with that found in healthy
      subjects) and 57% for SAA and IL-6 in only one-third of the patients. Increasing
      the number of measurements up to five did not change the reliability.
      CONCLUSIONS: Individual factors significantly influence the levels of
      inflammatory indexes in HD patients in periods free of inflammatory clinical
      events. The mean of two weekly CRP measurements, but not of SAA or IL-6, seems to
      assess microinflammation in most patients with a sufficient reliability.

PMID- 14671051
TI  - Increased hydrogen peroxide in the exhaled breath of uraemic patients unaffected
      by haemodialysis.
AB  - BACKGROUND: Uraemia is accompanied by conditions favouring the rise of H2O2
      activity in body fluids. This results from the increased release of H2O2 by
      polymorphonuclear leukocytes and decreased plasma glutathione peroxidase
      activity. The purpose of this study was to determine if patients on chronic
      haemodialysis (HD) exhale more H2O2 than healthy individuals, and if dialysis
      affects breath H2O2 content. METHODS: We studied 29 chronic HD patients (mean age
      49 +/- 11 years) and 40 healthy persons (mean age 44 +/- 9 years). H2O2, which is
      volatile, was measured fluorimetrically with the homovanillic acid method in the
      exhaled breath condensate (EBC) of the study cohort. EBC was collected
      immediately before and after the HD session and also at 20 and 60 min of HD
      treatment (n = 14) and once in controls. Peak expiratory flow (PEF), white blood
      cell (WBC) count, PaO(2) and circulatory cyclic guanosine monophosphate (cGMP),
      Il-6 and Il-8 concentrations were measured concomitantly. Finally, H2O2 diffusion
      through the dialyser cuprophane membrane was determined in an in vitro
      experiment. RESULTS: At baseline, EBC H2O2 concentration was 22 times higher in
      HD patients than in controls (2.92 +/- 4.64 vs 0.16 +/- 0.13 microM, P < 0.001).
      Although the maximum decrease in PEF (431 +/- 52 vs 398 +/- 56 l/min, P < 0.01)
      and WBC count (6.72 +/- 1.02 vs 3.82 +/- 1.51 x 10(3)/ microl, P < 0.01) occurred
      at 20 min after the start of HD, no significant changes in breath H2O2 levels
      were noted throughout the session. Plasma IL-6 and IL-8 levels remained unchanged
      whereas cGMP rose 1.3 times at 60 min (P < 0.01). In vitro, H2O2 rapidly diffused
      through the cuprophane membrane. CONCLUSION: Chronic HD patients exhale more H2O2
      than healthy subjects. Although no change of breath H2O2 concentration was
      observed during HD, as H2O2 easily diffuses through the dialyser membrane, it is
      not possible to rule out that HD stimulates H2O2 generation.

PMID- 14671052
TI  - Comparative analysis of procoagulatory activity of haemodialysis, haemofiltration
      and haemodiafiltration with a polysulfone membrane (APS) and with different modes
      of enoxaparin anticoagulation.
AB  - BACKGROUND: Treatment modalities of renal replacement therapy differ in their
      diffusive and convective mass transfer characteristics. It was the goal of this
      study to clarify whether an increase in convective mass transfer as performed
      with haemofiltration (HF) and haemodiafiltration (HDF) in comparison with high
      flux haemodialysis (HD) is associated with an alteration in procoagulatory
      activity or with complement activation. METHODS: Ten stable chronic HD patients
      were monitored during 120 treatments in a randomized cross over design. A high
      flux polysulfone dialyser (APS 900) was used for high-flux HD, pre-dilution HF
      and pre-dilution HDF. Constant flow of on-line substitution fluid for HF and HDF
      was 200 ml/min. The low molecular weight heparin (LMWH) enoxaparin was used for
      anticoagulation (i) as single bolus (50 IU/kg body weight, median 3700 IU) and
      (ii) as bolus of 1200 IU followed by a median continuous dose of 400 IU/h. Blood
      samples were collected before the LMWH bolus, after 10 min, 60 min, 120 min and
      at the end of treatment in venous and arterial blood lines to determine antiXa
      activity, thrombin-antithrombin-III complex (TAT), D-dimer and C5a generation.
      RESULTS: Net ultrafiltration did not significantly differ between HD, HF and HDF
      but total ultrafiltration in HF and HDF far exceeded total ultrafiltration in HD.
      With conditions of single bolus, or bolus and continuous anticoagulation with
      enoxaparin, after comparable treatment times (median duration 4.25 h), TAT and D
      dimer generation at identical anti-Xa levels revealed significantly higher
      coagulation activity during HF and HDF, compared with high-flux HD as assessed by
      comparative area under the curve (AUC) analysis. Plasma concentration of C5a in
      venous bloodlines did not significantly differ during HD, HF and HDF. CONCLUSION:
      A higher convective mass transfer during HF and HDF, in comparison with high-flux
      HD caused by a greater total ultrafiltration volume was associated with increased
      procoagulatory activity in the extracorporeal circuit. Molecular markers
      assessing the activation of coagulation are appropriate to adjust the
      anticoagulation regime to high UF volumes in order to minimize bleeding risk and
      optimize patency of the extracorporeal circuit.

PMID- 14671053
TI  - Regional citrate anticoagulation in continuous venovenous haemodiafiltration
      using commercial solutions.
AB  - BACKGROUND: Treatment with trisodium citrate provides an effective means of
      regional anticoagulation during continuous renal replacement therapy (CRRT). We
      evaluated the efficacy, safety and cost of a regional citrate anticoagulation
      protocol using commercial solutions in 17 critically ill patients treated with
      continuous venovenous haemodiafiltration (CVVHDF). We performed a total of 22
      sessions. METHODS: We delivered an A.C.D-A(541(R)) solution containing 112.9
      mmol/l disodium citrate (3.22%) at a median rate of 260 (190-280) ml/h via the
      pre-filter port of a COBE PRISMA with an AN-69 dialyser, while adjusting the rate
      to maintain post-filtered ionized calcium (iCa(2+)) between 0.25 and 0.4 mmol/l.
      Plasma iCa(2+) was maintained at >1.1 mmol/l by infusion of calcium chloride at a
      median rate of 1.70 (1.36-2.27) mmol/h. The dialysate was easily modified
      according to the acid-base status of each patient. Both replacement and dialysate
      solutions were delivered at 1200 ml/h. Each session was scheduled for 48 h and
      biological parameters were assessed every 6 h. RESULTS: The mean dialyser
      survival was 39 +/- 11 h (median 41.5 h; range 13-48 h). We observed dialyser
      clotting in four cases (18%). There were no bleeding events or modifications of
      coagulation parameters. The citrate solution, replacement solution and dialysate
      were obtained as commercial products. Both the replacement and dialysate
      solutions contained calcium. The extra cost of this technique was 25 euro;/day as
      compared to anticoagulation with heparin. CONCLUSIONS: We designed an efficient
      method of regional citrate anticoagulation for CVVHDF by using commercial
      solutions. The monitoring of patients was as intensive as during heparin
      anticoagulation for CRRT. Because of the higher cost of this method, it should be
      proposed only for patients with high bleeding risk.

PMID- 14671054
TI  - Lower risk for cardiovascular mortality in oral 1alpha-hydroxy vitamin D3 users
      in a haemodialysis population.
AB  - BACKGROUND: Renal failure results in deficiency of active vitamin D3 that has
      diverse effects on metabolism and organ functions. Treatment with active forms of
      vitamin D(3) ameliorates abnormalities in bone and mineral metabolism, cardiac
      function, immune response and others. We hypothesized that treatment with vitamin
      D(3) may be beneficial for survival in patients with end-stage renal disease
      (ESRD). METHODS: We compared the risk of death between regular users (n = 162)
      and non-users (n = 80) of oral 1alpha-hydroxyvitamin D3 (alfacalcidol) in a
      cohort of ESRD patients undergoing haemodialysis for a follow-up of 61 +/- 23
      months. The daily dose of alfacalcidol ranged from 0.25 to 1.5 microg, with a
      median of 0.5 microg. RESULTS: The alfacalcidol users showed a lower risk of
      death from cardiovascular disease than the non-users in a univariate Cox model
      [hazards ratio (HR) 0.287, 95% confidence interval (CI) 0.127-0.649, P = 0.003],
      whereas the risk for death from non-cardiovascular disease was not different
      between the two groups. Stepwise multivariate Cox analysis showed that
      cardiovascular mortality was significantly associated with age, presence of
      diabetes mellitus and treatment with alfacalcidol (HR 0.377, 95% CI 0.246-0.578,
      P = 0.022). CONCLUSIONS: These results indicate that use of oral alfacalcidol was
      associated with reduced risk for cardiovascular death in this cohort of ESRD
      patients. The result of this observational study warrants further randomized
      controlled trials with 1alpha-hydroxy vitamin D3 to confirm the possibility that
      such medication improves survival of ESRD patients.

PMID- 14671055
TI  - Inter-dialytic variations in blood volume and total body water in uraemic
      patients treated by dialysis.
AB  - BACKGROUND: An optimal balance of sodium and water is one of the most important
      goals of haemodialysis (HD) therapy. However, while inter-dialytic variations in
      blood volume (BV) have been well described, very little is known about the
      dynamics of fluid accumulation and distribution in body compartments during the
      inter-dialysis period. METHODS: We studied inter-dialysis variations in BV,
      measured as percent variation of plasma haemoglobin (Hb) concentrations (%
      triangle up BV) and percent variation of total body water (% triangle up TBW), in
      24 uraemic patients treated by standard bicarbonate dialysis. These parameters
      were determined at the end of the last weekly dialysis (T0), after 24 h (T1), 48
      h (T2), and at the beginning of the following dialysis session (T3). At each time
      point we measured Hb, haematocrit (Hct), serum albumin (sAlb), plasma sodium
      (Na), plasma potassium (K), blood urea nitrogen (BUN), plasma osmolality (Osm),
      body weight (BW), systolic blood pressure (SBP), diastolic blood pressure (DBP)
      and heart rate (HR). All patients were clinically stable and had no evidence of
      acute blood loss in the 3 weeks before the study. RESULTS: During the inter
      dialysis period, there were increases in BUN, K and Osm, but Na did not change.
      SBP and DBP also did not change. HR tended to decrease, and showed a significant
      reduction between T0 and T3. TBW increased in a linear fashion whereas BV
      increased exponentially, showing a slow rise during the first 24 h followed by a
      greater increase in the following time intervals. This was confirmed by
      concomitant but opposite percent variations in Hct and sAlb concentrations.
      CONCLUSIONS: Despite the limitations of the current methodology, our data show
      that the increase in TBW is redistributed during the long inter-dialysis period
      and this may prevent the effects of a too premature expansion of the intra
      vascular compartment. This is especially evident during the first 24 h after HD,
      during which % triangle up BV is lowest, indicating a preferential distribution
      of the fluid load towards the extra-vascular space. During the following time
      intervals, the extra-vascular compartment refills in conjunction with an
      exponential expansion of BV that reaches its maximum in the last 24 h before HD.

PMID- 14671056
TI  - Effect of cool temperature dialysate on the quality and patients' perception of
      haemodialysis.
AB  - BACKGROUND: The effects of cool dialysate on the urea reduction ratio (URR) in
      high efficiency haemodialysis have not been completely studied. After reviewing
      the literature, it appeared that patients' perceptions of cool dialysis have not
      been studied. Since patients' perception have an impact on patient satisfaction,
      this motivated the authors to research this area of practice. METHODS: This study
      was designed to determine whether a high URR and haemodynamic stability could be
      achieved by using cool dialysate in two groups of patients. The first group of
      five patients were known to have hypotension episodes during dialysis, and the
      second group of five patients were documented as having stable blood pressure
      (BP) during and after dialysis, after excluding vascular access recirculation and
      any other problems. Each patient was dialysed for three sessions using cool
      dialysate (35 degrees C) followed by another three sessions using a standard
      dialysate temperature (36.5 degrees C). All other dialysis session parameters
      were maintained. RESULTS: The results show that the dialysate cooling resulted in
      an increased ultrafiltration in the low BP group (P = 0.05). Cool dialysis had
      neither an adverse nor a beneficial effect on urea removal in the two groups (P =
      NS). The mean arterial pressure post- and intra-dialysis was significantly higher
      in dialysis with cool dialysate in the low BP group (P < 0.01 and P < 0.007,
      respectively). The mean arterial pressure in the stable BP group remained
      unchanged when cool dialysate was used (P = NS). The intra-dialytic pulse rates
      in the low and stable BP groups were similar. A total of seven episodes of
      symptomatic hypotension were observed in the low BP group, but none in the stable
      BP group (P < 0.0001). Patients' perceptions about cool dialysate were measured
      by a questionnaire which showed that 80% of them felt more energetic after
      dialysis and requested to be always dialysed with cool dialysate. CONCLUSION:
      Cool dialysate improves tolerance for dialysis in hypotensive patients and helps
      increase ultrafiltration while maintaining haemodynamic stability during and
      after dialysis. Patients' perceptions were positive, as most of the selected
      sample felt more energetic and generally well during and after dialysis, and this
      had a positive impact on their activities of daily living.

PMID- 14671057
TI  - Individualized bicarbonate concentrations in the peritoneal dialysis fluid to
      optimize acid-base status in CAPD patients.
AB  - BACKGROUND: A large percentage of peritoneal dialysis (PD) patients being treated
      with standard lactate-containing solutions tend to have serum bicarbonate
      concentrations below or above the normal range. The inter-patient variability of
      serum bicarbonate is a result of many influences and it may be appropriate to
      adjust the bicarbonate concentration in the peritoneal dialysis fluid (PDF) to
      the current serum bicarbonate in the individual patient. METHODS: Two
      concentrations of bicarbonate in PDF were compared in this study (34 and 39
      mmol/l). Eligible patients underwent a pre-study phase of 12 weeks to determine
      serum bicarbonate every six weeks. Sixty-one patients entered the stratification
      phase. Acidotic patients (serum venous bicarbonate <25.3 mmol/l) were allocated
      to the high bicarbonate solution, patients in the normal serum bicarbonate range
      or alkalotic patients (serum venous bicarbonate >25.3 mmol/l) to the low
      bicarbonate solution. Patients were followed up for 24 weeks, in which study
      visits were performed every 6 weeks to assess acid-base status, peritoneal and
      renal function, and to calculate protein nitrogen appearance rate (PNA). RESULTS:
      Patients with acidosis at baseline had higher body weight, body surface area,
      blood urea nitrogen, serum creatinine and PNA than patients with bicarbonate
      within the normal range or with alkalosis. They significantly improved their
      serum bicarbonate (23.45 +/- 2.5 vs 25.7 +/- 2.8 mmol/l, baseline vs week 24; P <
      0.01), whereas patients treated with the low bicarbonate PDF maintained their
      serum venous bicarbonate over the 24 week study period (27.77 +/- 2.9 vs 27.06 +/
      2.1 mmol/l, baseline vs week 24; P = NS). Analysing both study groups together,
      at baseline, 66% of the patients presented with mild to moderate acidosis, this
      figure at the end of the study was 23.4%. PNA did not change in the two groups;
      however, in the subgroup of patients (N = 23) in whom the 39 mmol/l PDF was
      effective in correcting metabolic acidosis, a decrease in PNA was observed.
      CONCLUSIONS: The study demonstrated that the individualized application of low
      and high bicarbonate PD PDFs allows one to achieve normal acid-base status in a
      large percentage of CAPD patients with potential benefits to nutritional status.

PMID- 14671058
TI  - Spousal renal donor transplantation in Chinese subjects: a 10 year experience
      from a single centre.
AB  - BACKGROUND: The shortage of cadaveric kidneys for renal transplantation is a
      particularly problematic situation in the locality of Hong Kong. Kidneys from
      spousal donors are therefore increasingly being used for transplantation. This
      study was undertaken to evaluate the outcome of spousal donor transplant
      recipients in comparison with that of genetically related living donor (LRD)
      allograft recipients. METHODS: From 1988, we have transplanted 22 spousal kidney
      recipients (group 1). All donors must demonstrate a genuine spousal relationship.
      Their outcome was compared with that of 24 LRD allograft recipients (group 2)
      transplanted in the same period with similar demographics, pre-transplant
      dialysis duration, immunosuppressive protocol and length of post-transplant
      follow-up. RESULTS: The mean (+/-SD) age was 36.5 +/- 8 and 32.5 +/- 6 years for
      groups 1 and 2, who were followed for 56.6 +/- 35 and 59.1 +/- 38 months,
      respectively. There was no difference in the incidence of delayed graft function,
      acute rejection and serum creatinine level at 5 years. Graft survival rates were
      86.4 and 79.2% (P = 0.56), while patient survival rates were 100 and 91.7% (P =
      0.171) at 5 years for groups 1 and 2, respectively. CONCLUSIONS: Spousal kidney
      transplantation shares comparable results with LRD transplantation and should be
      encouraged in places where cadaveric organs remain scarce. Stringent measures
      must be implemented to prevent the possible emergence of kidney bartering and to
      protect the interests of living donors. The ethical and social issues regarding
      the spousal donor in Hong Kong and other countries are discussed.

PMID- 14671059
TI  - A multicentre study of registration on renal transplantation waiting list of the
      elderly and patients with type 2 diabetes.
AB  - BACKGROUND: Studies in the USA have shown that some patients (African-Americans,
      women, the elderly and diabetics) were less likely to receive renal transplants.
      In order to identify patient characteristics modifying the likelihood of being
      wait-listed, we studied registration on renal transplantation waiting list (WLR)
      focusing on elderly (age > or =60 years) and on patients with type 2 diabetes
      (D2) in three departments of nephrology in the Rhone-Alpes county in France.
      METHODS: In a cohort of 549 patients who reached end-stage renal disease (ESRD)
      between 1995 and 1998 in these units, we analysed the rates of pre-transplant
      evaluation (PTE), the duration of PTE, the rates of exclusion from
      transplantation by PTE and the rates of WLR. With Cox regression model, we
      identified the characteristics that have independent and significant effects on
      the likelihood of being registered after the first renal replacement therapy
      (RRT). RESULTS: In this cohort, 185 patients (33.7%) were wait-listed by 31.03.00
      and no patient > or =70 years was evaluated or registered. In univariate
      analysis, PTE and WLR rates were lower in the elderly (21.5 and 20.0%,
      respectively) than those <60 years (79.1 and 70.2%, P < 0.001) and in D2 (33.0
      and 24.2%) than in non-D2 (65.8 and 60.6%, P < 0.001). The duration of PTE was
      longer in D2 than in non-D2 (12.7 +/- 11.0 vs 7.5 +/- 7.1 months, P < 0.01).
      Among patients excluded from PTE, more patients without relevant co-morbidities
      [e.g. rapidly progressive ESRD, cardiovascular disease (CVD), malignancy] were
      present in the elderly (> or =70 years: 14.8%; 60-69 years: 17.0%; <60 years:
      6.4%) and in D2 (18.0%) than in non-D2 (10.9%). The adjusted relative risks (aRR)
      of being wait-listed after first RRT were significantly lowered by age and D2
      (aRR, 95% CI): 60-64 year olds (0.44%: 0.26-0.75), 65-69 year olds (0.07%: 0.03
      0.20) and D2 (0.41%: 0.24-0.69). Other conditions associated with a lower aRR
      were rapidly progressive ESRD (0.21%: 0.08-0.55), CVD (0.59%: 0.36-0.94),
      malignancy (0.13%: 0.04-0.46) and psychosis (0.05%: 0.01-0.35). CONCLUSION:
      Advanced age and D2 were associated with low PTE and WLR rates even after
      adjustment for other patient characteristics.

PMID- 14671060
TI  - The value of C2 monitoring in stable renal allograft recipients on maintenance
      immunosuppression.
AB  - BACKGROUND: Cyclosporin A (CyA) is a drug with a narrow therapeutic window and
      highly variable pharmacokinetics. Therapeutic drug monitoring is essential and
      conventionally has been guided by trough levels (C0). Recent evidence indicates
      that a single blood concentration measurement 2 h after CyA administration (C2)
      is a more accurate predictor of drug exposure and clinical events than
      determination of C0. To date, limited prospective data are available with respect
      to risks and benefits of C2 monitoring in renal transplant recipients, and little
      experience exists with C2 monitoring in maintenance patients. METHODS: In 127
      long-term renal allograft recipients, we determined C2 levels in addition to
      conventional C0 and observed clinical outcome over a period of 13.6 +/- 3.1
      months. To determine the precision of monitoring, we repeatedly determined C0 and
      C2 levels in 46 stable patients without dose change. RESULTS: Clinical outcome
      was excellent (patient survival 100%, graft survival 97%), with only two
      borderline rejections, although C2 levels (564 +/- 186 ng/ml) were lower than
      recommended so far for maintenance patients. We found no significant differences
      in C2 levels between patients with rejection and CyA toxicity. Receiver operating
      characteristic (ROC) analysis showed no prediction for risk of rejection,
      toxicity or infection by C2 levels. Repeated determinations of both C0 and C2
      levels in 46 patients revealed a high intra-patient variability. In these
      patients, the coefficient of variation for C2 was only marginally better compared
      with C0. CONCLUSIONS: We conclude that in maintenance patients, C2 concentrations
      between 500 and 600 ng/ml are well tolerated and provide effective and safe
      rejection prophylaxis. Although mean C2 levels do not seem to be helpful in
      identifying patients at risk for rejection, they may be useful to detect over
      immunosuppression and to improve long-term allograft survival further by reducing
      CyA nephrotoxicity.

PMID- 14671061
TI  - Prophylactic bilateral nephrectomies in two paediatric patients with missense
      mutations in the WT1 gene.
AB  - BACKGROUND: Denys-Drash syndrome (DDS) is associated with mutations of the Wilms'
      tumour 1 (WT1) gene, and is characterized by pseudohermaphroditism, a progressive
      glomerulopathy, and the development of Wilms' tumour. More than 90% of patients
      with DDS who carry constitutional intragenic WT1 mutations are at high risk (90%)
      for the development of Wilms' tumour. WT1 is a signalling protein with 90% of WT1
      mutations occurring in the WT1 zinc finger region as single nucleotide
      polymorphisms, the majority of which are missense mutations. METHODS:
      Constitutional DNA was extracted from peripheral blood. Direct sequencing and
      restriction enzymes were employed to analyse mutations. RESULTS: Two children,
      46XY males who had evidence of pseudohermaphroditism, hypogonadism and renal
      failure with a glomerulopathy atypical for DDS, but no Wilms' tumour or
      nephroblastomatosis, on investigation, prior to transplant, were identified with
      missense mutations in the WT1 gene, in exons 8 and 9, respectively. The decision
      to do prophylactic nephrectomies was based on the genetic identification of WT1
      mutations supporting a diagnosis of incomplete DDS, with the potential for
      increased risk of malignancy with the development of Wilms' tumour. The
      nephrectomy specimens demonstrated nephrogenic rests (nephroblastomatosis), which
      have a potential for malignant transformation. CONCLUSIONS: WT1 missense
      mutations in exons 8 and 9 can be regarded as having the potential for malignant
      change supporting prophylactic nephrectomy in apparent incomplete DDS patients
      with end-stage renal disease.

PMID- 14671062
TI  - The walking man with a completely occluded aorta.

PMID- 14671063
TI  - Familial mesangio-capillary glomerulonephritis with initial presentation as
      haemolytic uraemic syndrome.

PMID- 14671064
TI  - Microscopic polyangiitis: first report of a case with onset during pregnancy.

PMID- 14671066
TI  - Isolated sphenoid sinusitis complicated by meningitis and multiple cerebral
      infarctions in a renal transplant recipient.

PMID- 14671065
TI  - Reverse seroconversion of hepatitis B in a haemodialysis patient.

PMID- 14671067
TI  - Successful treatment due to vacuum seal technique of a severe Scedosporium
      apiospermum skin infection in a renal transplant recipient.

PMID- 14671069
TI  - Creutzfeldt-Jakob-like EEG in a patient with end-stage renal failure.

PMID- 14671068
TI  - Double nucleotidic mutation of the MYH9 gene in a young patient with end-stage
      renal disease.

PMID- 14671070
TI  - Sudden development of low tolerance of dialysis in a young female patient.

PMID- 14671071
TI  - Superior vena caval obstruction following central venous cannulation.

PMID- 14671072
TI  - Marcel Legrain (1923-2003).

PMID- 14671073
TI  - Post-transplant erythrocytosis and thromboembolic events: an error.

PMID- 14671075
TI  - Atherosclerotic renal artery stenosis in patients starting dialysis: an emperor
      with no clothes.

PMID- 14671077
TI  - Angiotensin II-induced proteinuria and expression of the podocyte slit pore
      membrane protein, nephrin.

PMID- 14671078
TI  - Pseudoephedrine urolithiasis associated with acute renal failure.

PMID- 14671079
TI  - The first reported case of successful pregnancy in a haemodialysis patient in
      Yemen.

PMID- 14671082
TI  - Generation and characterization of closely related epizootic and enzootic
      infectious cDNA clones for studying interferon sensitivity and emergence
      mechanisms of Venezuelan equine encephalitis virus.
AB  - Venezuelan equine encephalitis virus (VEEV) is a reemerging pathogen and a
      continuing threat to humans and equines in the Americas. Identification of the
      genetic determinants that enable epizootic VEEV strains to arise and exploit
      equines as amplification hosts to cause widespread human disease is pivotal to
      understanding VEE emergence. The sensitivity to murine alpha/beta interferon
      mediated antiviral activity was previously correlated to the epizootic phenotype
      of several VEEV strains. Infectious cDNA clones were generated from an epizootic
      subtype IC VEEV strain (SH3) isolated during the 1992 Venezuelan outbreak and a
      closely related enzootic, sympatric subtype ID strain (ZPC738). These VEEV
      strains had low-cell-culture-passage histories and differed by only 12 amino
      acids in the nonstructural and structural proteins. Rescued viruses showed
      similar growth kinetics to their parent viruses in several cell lines, and murine
      infections resulted in comparable viremia and disease. Unlike what was found in
      other studies of epizootic and enzootic VEEV strains, the sensitivities to murine
      alpha/beta interferon did not differ appreciably between these epizootic versus
      enzootic strains, calling into question the reliability of interferon sensitivity
      as a marker of epizootic potential.

PMID- 14671083
TI  - Long-term transgene expression in proliferating cells mediated by episomally
      maintained high-capacity adenovirus vectors.
AB  - High-capacity "gutless" adenovirus vectors (HC-AdV) mediate long-term transgene
      expression in resting cells in vitro and in vivo because of low toxicity and
      immunogenicity. However, in proliferating cells, expression is transient since HC
      AdV genomes do not possess elements that allow for replication and segregation of
      the replicated genomes to daughter cells. We developed a binary HC-AdV system
      that, under certain conditions, allows for significantly prolonged episomal
      maintenance of HC-AdV genomes in proliferating tissue culture cells, resulting in
      sustained transgene expression. After transduction of target cells the linear HC
      AdV genomes were circularized by the DNA recombinase FLPe, which was expressed
      from the second HC-AdV. The oriP/EBNA-1 replication system derived from Epstein
      Barr virus, as well as the human replication origin from the lamin B2 locus, were
      used as cis elements to test for replication of the 28-kb circular vector genomes
      with or without selective pressure. Depending on the system, up to 98% of the
      circularized genomes were replicated and segregated to daughter cells, as
      demonstrated by Southern assays and as confirmed by monitoring EGFP transgene
      expression. Surprisingly, in the absence of FLPe recombinase, a small but
      significant number of HC-AdV genomes spontaneously circularized after
      transduction of target cells. These circles, found to contain end-to-end joined
      adenovirus termini, replicated with increased efficiency compared to vectors
      circularized by FLPe. After further improvements, this HC-AdV system might be
      suitable for gene therapy applications requiring long-term transgene expression.

PMID- 14671084
TI  - ICP27 selectively regulates the cytoplasmic localization of a subset of viral
      transcripts in herpes simplex virus type 1-infected cells.
AB  - Evidence suggests that the herpes simplex virus regulatory protein ICP27 mediates
      the nuclear export of viral transcripts; however, the extent of this activity
      during infection is unclear. ICP27 is required for efficient expression of the
      long, leaky-late UL24 transcripts, but not for that of the short, early UL24
      transcripts. We found that infection by an ICP27-null mutant resulted in
      undetectable UL24 protein expression, which represented at least a 70-fold
      decrease relative to that of wild-type virus. Because lack of ICP27 had a greater
      effect on levels of UL24 protein than on transcripts, we examined its effect on
      subcellular localization of UL24 transcripts. In wild-type-infected cells, both
      short and long UL24 transcripts fractionated predominantly with the cytoplasm.
      However, in the absence of ICP27, greater than 50% of long UL24 transcripts were
      nuclear, while the percentage of short UL24 transcripts that were cytoplasmic was
      not reduced. These results also imply that the short UL24 transcripts are
      translated poorly. The effect of ICP27 on cytoplasmic localization of the long
      UL24 transcripts did not extend to other transcripts with which it shared a
      common 3' end or to other transcripts tested, including gC and UL42, whose
      overall expression is highly dependent on ICP27. Thus, the dual effects of ICP27
      on mRNA accumulation and cytoplasmic localization are not always linked. These
      results identify viral transcripts that are dependent on ICP27 for efficient
      cytoplasmic localization during infection, but they also indicate the existence
      of ICP27-independent nuclear export pathways that are accessible to many viral
      transcripts during infection.

PMID- 14671085
TI  - Cholesterol removal by methyl-beta-cyclodextrin inhibits poliovirus entry.
AB  - Upon binding to the poliovirus receptor (PVR), the poliovirus 160S particles
      undergo a conformational transition to generate 135S particles, which are
      believed to be intermediates in the virus entry process. The 135S particles
      interact with host cell membranes through exposure of the N termini of VP1 and
      the myristylated VP4 protein, and successful cytoplasmic delivery of the genomic
      RNA requires the interaction of these domains with cellular membranes whose
      identity is unknown. Because detergent-insoluble microdomains (DIMs) in the
      plasma membrane have been shown to be important in the entry of other
      picornaviruses, it was of interest to determine if poliovirus similarly required
      DIMs during virus entry. We show here that methyl-beta-cyclodextrin (MbetaCD),
      which disrupts DIMs by depleting cells of cholesterol, inhibits virus infection
      and that this inhibition was partially reversed by partially restoring
      cholesterol levels in cells, suggesting that MbetaCD inhibition of virus
      infection was mediated by removal of cellular cholesterol. However, fractionation
      of cellular membranes into DIMs and detergent-soluble membrane fractions showed
      that both PVR and poliovirus capsid proteins localize not to DIMs but to
      detergent-soluble membrane fractions during entry into the cells, and their
      localization was unaffected by treatment with MbetaCD. We further demonstrate
      that treatment with MbetaCD inhibits RNA delivery after formation of the 135S
      particles. These data indicate that the cholesterol status of the cell is
      important during the process of genome delivery and that these entry pathways are
      distinct from those requiring DIM integrity.

PMID- 14671086
TI  - Identification and characterization of novel, naturally processed measles virus
      class II HLA-DRB1 peptides.
AB  - Previously, we identified a naturally processed and presented measles virus (MV)
      19-amino-acid peptide, ASDVETAEGGEIHELLRLQ (MV-P), derived from the
      phosphoprotein and eluted from the human leukocyte antigen (HLA) class II
      molecule by using mass spectrometry. We report here the identification of a 14
      amino-acid peptide, SAGKVSSTLASELG, derived from the MV nucleoprotein (MV-N)
      bound to HLA-DRB1*0301. Peripheral blood mononuclear cells (PBMC) from 281
      previously vaccinated measles-mumps-rubella II (MMR-II) subjects (HLA discordant)
      were studied for peptide recognition by T cells. Significant gamma interferon
      (IFN-gamma) responses to MV-P and MV-N peptides were observed in 55.9 and 15.3%
      of subjects, respectively. MV-P- and MV-N-specific interleukin-4 (IL-4) responses
      were detected in 19.2 and 23.1%, respectively, of PBMC samples. Peptide-specific
      cytokine responses and HLA-DRB1 allele associations revealed that, for the MV-P
      peptide, the allele with the strongest association with both IFN-gamma (P = 0.02)
      and IL-4 (P = 0.03) secretion was DRB1*0301. For MV-N, the allele with the
      strongest association with IFN-gamma secretion was DRB1*1501 (P = 0.04), and the
      alleles with the strongest associations with IL-4 secretion were DRB1*1103 and
      DRB1*1303 (P = 0.01). These results indicate that HLA class II MV proteins can be
      processed, presented, and identified, and the ability to generate cell-mediated
      immune responses can be demonstrated. This information is promising for new
      vaccine design strategies with peptide-based vaccines.

PMID- 14671087
TI  - Nucleic acid binding-induced Gag dimerization in the assembly of Rous sarcoma
      virus particles in vitro.
AB  - As also found for other retroviruses, the Rous sarcoma virus structural protein
      Gag is necessary and sufficient for formation of virus-like particles (VLPs).
      Purified polypeptide fragments comprising most of Gag spontaneously assemble in
      vitro at pH 6.5 into VLPs lacking a membrane, a process that requires nucleic
      acid. We showed previously that the minimum length of a DNA oligonucleotide that
      can support efficient assembly is 16 nucleotides (nt), twice the protein's
      binding site size. This observation suggests that the essential role of nucleic
      acid in assembly is to promote the formation of Gag dimers. In order to gain
      further insight into the role of dimerization, we have studied the assembly
      properties of two proteins, a nearly full-length Gag (deltaMBDdeltaPR) capable of
      proper in vitro assembly and a smaller Gag fragment (CTD-NC) capable of forming
      only irregular aggregates but with the same pH and oligonucleotide length
      requirements as for assembly with the larger protein. In analyses by
      sedimentation velocity and by cross-linking, both proteins remained monomeric in
      the absence of oligonucleotides or in the presence of an oligonucleotide of
      length 8 nt (GT8). At pH 8, which does not support assembly, binding to GT16
      induced the formation of dimers of deltaMBDdeltaPR but not of CTD-NC, implying
      that dimerization requires the N-terminal domain of the capsid moiety of Gag.
      Assembly of VLPs was induced by shifting the pH of dimeric complexes of
      deltaMBDdeltaPR and GT16 from 8 to 6.5. An analogue of GT16 with a ribonucleotide
      linkage in the middle also supported dimer formation at pH 8. Even after
      quantitative cleavage of the oligonucleotide by treatment of the complex with
      RNase, these dimers could be triggered to undergo assembly by pH change. This
      result implies that protein-protein interactions stabilize the dimer. We propose
      that binding of two adjacent Gag molecules on a stretch of nucleic acid leads to
      protein-protein interactions that create a Gag dimer and that this species has an
      exposed surface not present in monomers which allows polymerization of the dimers
      into a spherical shell.

PMID- 14671088
TI  - Selection of functional 5' cis-acting elements promoting efficient sindbis virus
      genome replication.
AB  - The 5' portion of the Sindbis virus (SIN) genome RNA is multifunctional. Besides
      initiating translation of the nonstructural polyprotein, RNA elements in the 5'
      200 bases of the SIN genome RNA, or its complement at the 3' end of the negative
      strand intermediate, play key roles in the synthesis of both negative- and
      positive-strand RNAs. We used here a combination of genetic and biochemical
      approaches to further dissect the functions of this sequence. Replacement of the
      SIN 5' end in defective-interfering (DI) and genome RNAs with sequences from a
      distantly related alphavirus, Semliki Forest virus (SFV), resulted in nonviable
      chimeras. The addition of five nucleotides from the 5' terminus of SIN restored
      negative-strand RNA synthesis in DI genomes but not their replication in vivo.
      Pseudorevertants of various SFV-SIN chimeras were isolated, and suppressor
      mutations were mapped to AU-rich sequences added to the 5' end of the original
      SFV 5' sequence or its "deleted" versions. Early pseudorevertants had
      heterogeneous 5' termini that were inefficient for replication relative to the
      parental SIN 5' sequence. In contrast, passaging of these pseudorevertant viral
      populations in BHK cells under competitive conditions yielded evolved, more
      homogeneous 5'-terminal sequences that were highly efficient for negative-strand
      synthesis and replication. These 5'-terminal sequences always began with 5'-AU,
      followed by one or more AU repeats or short stretches of oligo(A). Further
      analysis demonstrated a positive correlation between the number of repeat units
      and replication efficiency. Interestingly, some 5' modifications restored high
      level viral replication in BHK-21 cells, but these viruses were impaired for
      replication in the cells of mosquito origin. These studies provide new
      information on sequence determinants required for SIN RNA replication and suggest
      new strategies for restricting cell tropism and optimizing the packaging of
      alphavirus vectors.

PMID- 14671089
TI  - Mosaic evolution of the severe acute respiratory syndrome coronavirus.
AB  - Severe acute respiratory syndrome (SARS) is a deadly form of pneumonia caused by
      a novel coronavirus, a viral family responsible for mild respiratory tract
      infections in a wide variety of animals including humans, pigs, cows, mice, cats,
      and birds. Analyses to date have been unable to identify the precise origin of
      the SARS coronavirus. We used Bayesian, neighbor-joining, and split decomposition
      phylogenetic techniques on the SARS virus replicase, surface spike, matrix, and
      nucleocapsid proteins to reveal the evolutionary origin of this recently emerging
      infectious agent. The analyses support a mammalian-like origin for the replicase
      protein, an avian-like origin for the matrix and nucleocapsid proteins, and a
      mammalian-avian mosaic origin for the host-determining spike protein. A bootscan
      recombination analysis of the spike gene revealed high nucleotide identity
      between the SARS virus and a feline infectious peritonitis virus throughout the
      gene, except for a 200- base-pair region of high identity to an avian sequence.
      These data support the phylogenetic analyses and suggest a possible past
      recombination event between mammalian-like and avian-like parent viruses. This
      event occurred near a region that has been implicated to be the human receptor
      binding site and may have been directly responsible for the switch of host of the
      SARS coronavirus from animals to humans.

PMID- 14671090
TI  - Alternative polyadenylation of adeno-associated virus type 5 RNA within an
      internal intron is governed by both a downstream element within the intron 3'
      splice acceptor and an element upstream of the P41 initiation site.
AB  - Adeno-associated virus type 5 (AAV5) has a linear, single-stranded DNA genome of
      ca. 5 kb and an overlapping transcription profile featuring multiple promoters
      and a single intron in the center of the genome. Unlike the situation for the
      prototype AAV2, AAV5 RNAs transcribed from upstream promoters at map units 7 (P7)
      and 19 (P19), which encode the viral Rep proteins, are predominantly
      polyadenylated at a site within the intron [(pA)p]. RNAs generated from the AAV5
      capsid gene promoter P41, which is only 78 nucleotides (nt) upstream of the
      intron donor, and 281 nt upstream of (pA)p, primarily readthrough (pA)p, are
      polyadenylated at a more distal site at the 3' end of the genome [(pA)d] and
      ultimately spliced. The intron contains the core sequences sufficient for
      polyadenylation at (pA)p, which is governed by a G/U-rich downstream element that
      overlaps with the intron 3' A2 splice acceptor. In addition, polyadenylation of
      P7- and P19-generated RNAs at (pA)p is influenced by an upstream element that
      lies 5' to the start of the P41 transcript. Our results also suggest that
      splicing and polyadenylation of P41-generated RNA can compete for the same pool
      of precursor pre-mRNA molecules. The cis-acting signals within the A2 3' splice
      site that govern polyadenylation and splicing of AAV5 RNAs must be optimized to
      program both (i) the levels of polyadenylation of P7- and P19-generated RNA at
      (pA)p required to generate the proper levels of the essential Rep proteins and
      (ii) the splicing of P41-generated RNAs to generate the proper ratio of capsid
      proteins during AAV5 infection.

PMID- 14671092
TI  - Inhibition of S-phase cyclin-dependent kinase activity blocks expression of
      Epstein-Barr virus immediate-early and early genes, preventing viral lytic
      replication.
AB  - The induction of lytic replication of the Epstein-Barr virus (EBV) completely
      arrests cell cycle progression, in spite of elevation of S-phase cyclin-dependent
      kinase (CDK) activity, thereby causing accumulation of hyperphosphorylated forms
      of retinoblastoma (Rb) protein (A. Kudoh, M. Fujita, T. Kiyono, K. Kuzushima, Y.
      Sugaya, S. Izuta, Y. Nishiyama, and T. Tsurumi, J. Virol. 77:851-861, 2003).
      Thus, the EBV lytic program appears to promote specific cell cycle-associated
      activity involved in the progression from G1 to S phase. We have proposed that
      this provides a cellular environment that is advantageous for EBV productive
      infection. Purvalanol A and roscovitine, inhibitors of S-phase CDKs, blocked the
      viral lytic replication when cells were treated at the early stage of lytic
      infection, while well-characterized inhibitors of enzymes, such as mitogen
      activated protein kinase, phosphatidylinositol 3-kinase, and protein kinase C,
      known to be involved in BZLF1 gene expression did not. Inhibition of CDK activity
      resulted in the accumulation of the hypophosphorylated form of Rb protein and
      inhibition of expression of EBV immediate-early and early proteins. Cycloheximide
      block-and-release experiments clearly demonstrated that even in the presence of
      enough amounts of the BZLF1 protein, purvalanol A blocked expression of lytic
      viral proteins at transcription level. Furthermore, reporter gene experiments
      confirmed that BZLF1-induced activation of early EBV promoters was impaired in
      the presence of the CDK inhibitor. We conclude here that the EBV lytic program
      promotes specific cell cycle-associated activity involved in the progression from
      G1 to S phase because the S-phase-like cellular environment is essential for the
      expression of immediate-early and early genes supplying the viral replication
      proteins and hence for lytic viral replication.

PMID- 14671091
TI  - Human immunodeficiency virus type 1 superinfection was not detected following 215
      years of injection drug user exposure.
AB  - Evidence for human immunodeficiency virus type 1 (HIV-1) superinfection was
      sought among 37 HIV-1-positive street-recruited active injection drug users
      (IDUs) from the San Francisco Bay area. HIV-1 sequences from pairs of samples
      collected 1 to 12 years apart, spanning a total of 215 years of exposure, were
      generated at p17 gag, the V3-V5 region of env, and/or the first exon of tat and
      phylogenetically analyzed. No evidence of HIV-1 superinfection was detected in
      which a highly divergent HIV-1 variant emerged at a frequency >20% of the serum
      viral quasispecies. Based on the reported risk behavior of the IDUs and the HIV-1
      incidence in uninfected subjects in the same cohort, a total of 3.4 new
      infections would have been expected if existing infection conferred no protection
      from superinfection. Adjusted for risk behaviors, the estimated relative risk of
      superinfection compared with initial infection was therefore 0.0 (95% confidence
      interval, 0.00, 0.79; P = 0.02), indicating that existing infection conferred a
      statistically significant level of protection against superinfection with an HIV
      1 strain of the same subtype, which was between 21 and 100%.

PMID- 14671093
TI  - Vaccination of rabbits with an adenovirus vector expressing the papillomavirus E2
      protein leads to clearance of papillomas and infection.
AB  - Cervical cancer arises from lesions caused by infection with high-risk types of
      human papillomavirus (HPV). Therefore, vaccination against HPV could prevent
      carcinogenesis by preventing HPV infection or inducing lesion regression. HPV E2
      protein is an attractive candidate for vaccine development because it is required
      for papilloma formation, is involved in all stages of the virus life cycle, and
      is expressed in all premalignant lesions as well as some cancers. This study
      reports vaccination against E2 protein using a rabbit model of papillomavirus
      infection. A recombinant adenovirus (Ad) vector expressing the E2 protein of
      cottontail rabbit papillomavirus (CRPV) was tested for therapeutic efficacy in
      CRPV-infected rabbits. Primary immunization with the Ad-E2 vaccine, compared to
      immunization with a control Ad vector, reduced the number of papilloma-forming
      sites from 17 of 45 to 4 of 45. After booster immunization, vaccinated rabbits
      formed no new papillomas versus an additional 23 papillomas in rabbits that
      received the control vector. Papillomas in the Ad-E2 vaccinees were significantly
      smaller than those in the control rabbits, and all four papillomas in the Ad-E2
      vaccinated rabbits regressed. No CRPV DNA was detected either in the regression
      sites or in sites that did not form papillomas, indicating that the vaccination
      led to clearance of CRPV from all infected sites.

PMID- 14671094
TI  - The baculovirus GP64 protein mediates highly stable infectivity of a human
      respiratory syncytial virus lacking its homologous transmembrane glycoproteins.
AB  - Baculovirus GP64 is a low-pH-dependent membrane fusion protein required for virus
      entry and cell-to-cell transmission. Recently, GP64 has generated interest for
      practical applications in mammalian systems. Here we examined the membrane fusion
      function of GP64 from Autographa californica multiple nucleopolyhedrovirus
      (AcMNPV) expressed in mammalian cells, as well as its capacity to functionally
      complement a mammalian virus, human respiratory syncytial virus (HRSV). Both
      authentic GP64 and GP(64/F), a chimeric protein in which the GP64 cytoplasmic
      tail domain was replaced with the 12 C-terminal amino acids of the HRSV fusion
      (F) protein, induced low-pH-dependent cell-cell fusion when expressed transiently
      in HEp-2 (human) cells. Levels of surface expression and syncytium formation were
      substantially higher at 33 degrees C than at 37 degrees C. The open reading
      frames (ORFs) encoding GP64 or GP(64/F), along with two marker ORFs encoding
      green fluorescent protein (GFP) and beta-glucuronidase (GUS), were used to
      replace all three homologous transmembrane glycoprotein ORFs (small hydrophobic
      SH, attachment G, and F) in a cDNA of HRSV. Infectious viruses were recovered
      that lacked the HRSV SH, G, and F proteins and expressed instead the GP64 or
      GP(64/F) protein and the two marker proteins GFP and GUS. The properties of these
      viruses, designated RSDeltaSH,G,F/GP64 or RSDeltaSH,G,F/GP(64/F), respectively,
      were compared to a previously described HRSV expressing GFP in place of SH but
      still containing the wild-type HRSV G and F proteins (RSDeltaSH [A. G. Oomens, A.
      G. Megaw, and G. W. Wertz, J. Virol., 77:3785-3798, 2003]). By immunoelectron
      microscopy, the GP64 and GP(64/F) proteins were shown to incorporate into HRSV
      induced filaments at the cell surface. Antibody neutralization, ammonium chloride
      inhibition, and replication levels in cell culture showed that both GP64 proteins
      efficiently mediated infectivity of the respective viruses in a temperature
      sensitive, low-pH-dependent manner. Furthermore, RSDeltaSH,G,F/GP64 and
      RSDeltaSH,G,F/GP(64/F) replicated to higher levels and had significantly higher
      stability of infectivity than HRSVs containing the homologous HRSV G and F
      proteins. Thus, GP64 and a GP64/HRSV F chimeric protein were functional and
      efficiently complemented an unrelated human virus in mammalian cells, producing
      stable, infectious virus stocks. These results demonstrate the potential of GP64
      for both practical applications requiring stable pseudotypes in mammalian systems
      and for studies of viral glycoprotein requirements in assembly and pathogenesis.

PMID- 14671095
TI  - Role for bovine viral diarrhea virus Erns glycoprotein in the control of
      activation of beta interferon by double-stranded RNA.
AB  - Production of alpha/beta interferon in response to viral double-stranded RNA
      (dsRNA) produced during viral replication is a first line of defense against
      viral infections. Here we demonstrate that the Erns glycoprotein of the
      pestivirus bovine viral diarrhea virus can act as an inhibitor of dsRNA-induced
      responses of cells. This effect is seen whether Erns is constitutively expressed
      in cells or exogenously added to the culture medium. The Erns effect is specific
      to dsRNA since activation of NF-kappaB in cells infected with Semliki Forest
      virus or treated with tumor necrosis factor alpha was not affected. We also show
      that Erns contains a dsRNA-binding activity, and its RNase is active against
      dsRNA at a low pH. Both the dsRNA binding and RNase activities are required for
      the inhibition of dsRNA signaling, and we discuss here a model to account for
      these observations.

PMID- 14671096
TI  - A single injection of recombinant measles virus vaccines expressing human
      immunodeficiency virus (HIV) type 1 clade B envelope glycoproteins induces
      neutralizing antibodies and cellular immune responses to HIV.
AB  - The anchored and secreted forms of the human immunodeficiency virus type 1 (HIV
      1) 89.6 envelope glycoprotein, either complete or after deletion of the V3 loop,
      were expressed in a cloned attenuated measles virus (MV) vector. The recombinant
      viruses grew as efficiently as the parental virus and expressed high levels of
      the HIV protein. Expression was stable during serial passages. The immunogenicity
      of these recombinant vectors was tested in mice susceptible to MV and in
      macaques. High titers of antibodies to both MV and HIV-Env were obtained after a
      single injection in susceptible mice. These antibodies neutralized homologous
      SHIV89.6p virus, as well as several heterologous HIV-1 primary isolates. A gp160
      mutant in which the V3 loop was deleted induced antibodies that neutralized
      heterologous viruses more efficiently than antibodies induced by the native
      envelope protein. A high level of CD8+ and CD4+ cells specific for HIV gp120 was
      also detected in MV-susceptible mice. Furthermore, recombinant MV was able to
      raise immune responses against HIV in mice and macaques with a preexisting anti
      MV immunity. Therefore, recombinant MV vaccines inducing anti-HIV neutralizing
      antibodies and specific T lymphocytes responses deserve to be tested as a
      candidate AIDS vaccine.

PMID- 14671097
TI  - Residues of human cytomegalovirus DNA polymerase catalytic subunit UL54 that are
      necessary and sufficient for interaction with the accessory protein UL44.
AB  - The human cytomegalovirus DNA polymerase contains a catalytic subunit, UL54, and
      an accessory protein, UL44. Recent studies suggested that UL54 might interact via
      its extreme C terminus with UL44 (A. Loregian, R. Rigatti, M. Murphy, E.
      Schievano, G. Palu', and H. S. Marsden, J. Virol. 77:8336-8344, 2003). To address
      this hypothesis, we quantitatively measured the binding of peptides corresponding
      to the extreme C terminus of UL54 to UL44 by using isothermal titration
      calorimetry. A peptide corresponding to the last 22 residues of UL54 was
      sufficient to bind specifically to UL44 in a 1:1 complex with a dissociation
      constant of ca. 0.7 microM. To define individual residues in this segment that
      are crucial for interacting with UL44, we engineered a series of mutations in the
      C-terminal region of UL54. The UL54 mutants were tested for their ability to
      interact with UL44 by glutathione S-transferase pulldown assays, for basal DNA
      polymerase activity, and for long-chain DNA synthesis in the presence of UL44. We
      observed that deletion of the C-terminal segment or substitution of alanine for
      Leu1227 or Phe1231 in UL54 greatly impaired both the UL54-UL44 interaction in
      pulldown assays and long-chain DNA synthesis without affecting basal polymerase
      activity, identifying these residues as important for subunit interaction. Thus,
      like the herpes simplex virus UL30-UL42 interaction, a few specific side chains
      in the C terminus of UL54 are crucial for UL54-UL44 interaction. However, the
      UL54 residues important for interaction with UL44 are hydrophobic and not basic.
      This information might aid in the rational design of new drugs for the treatment
      of human cytomegalovirus infection.

PMID- 14671099
TI  - Inefficient signalase cleavage promotes efficient nucleocapsid incorporation into
      budding flavivirus membranes.
AB  - The mechanism for efficient nucleocapsid (NC) uptake into flavivirus particles
      which form by budding through the membranes of the endoplasmic reticulum (ER) was
      investigated by using Murray Valley encephalitis virus as a model. Budding of
      flavivirus membranes is driven by the viral transmembrane proteins prM and E
      independently of NC interaction. We show that control of signalase cleavage of
      the multimembrane-spanning flavivirus polyprotein by the catalytic function of
      the viral protease is critical for efficient virus morphogenesis. In wild-type
      virus, signalase cleavage of prM remains inefficient until cleavage of capsid at
      the cytosolic side of the signal sequence separating the two proteins has
      occurred. This obligatory sequence of cleavages was uncoupled in a mutant virus
      with the consequence of greatly reduced incorporation of NC into budding
      membranes and augmented release of NC-free virus-like particles. Efficient
      signalase cleavage of prM in the mutant virus resulted in partial inhibition of
      cleavage of capsid by the viral NS2B-3 protease. Our results support a model for
      flavivirus morphogenesis involving temporal and spatial coordination of NC
      assembly and envelopment by regulated cleavages of an ER membrane-spanning capsid
      prM intermediate.

PMID- 14671098
TI  - Genomes of the parapoxviruses ORF virus and bovine papular stomatitis virus.
AB  - Bovine papular stomatitis virus (BPSV) and orf virus (ORFV), members of the genus
      Parapoxvirus of the Poxviridae, are etiologic agents of worldwide diseases
      affecting cattle and small ruminants, respectively. Here we report the genomic
      sequences and comparative analysis of BPSV strain BV-AR02 and ORFV strains OV
      SA00, isolated from a goat, and OV-IA82, isolated from a sheep. Parapoxvirus
      (PPV) BV-AR02, OV-SA00, and OV-IA82 genomes range in size from 134 to 139 kbp,
      with an average nucleotide composition of 64% G+C. BPSV and ORFV genomes contain
      131 and 130 putative genes, respectively, and share colinearity over 127 genes,
      88 of which are conserved in all characterized chordopoxviruses. BPSV and ORFV
      contain 15 and 16 open reading frames (ORFs), respectively, which lack similarity
      to other poxvirus or cellular proteins. All genes with putative roles in
      pathogenesis, including a vascular endothelial growth factor (VEGF)-like gene,
      are present in both viruses; however, BPSV contains two extra ankyrin repeat
      genes absent in ORFV. Interspecies sequence variability is observed in all
      functional classes of genes but is highest in putative virulence/host range
      genes, including genes unique to PPV. At the amino acid level, OV-SA00 is 94%
      identical to OV-IA82 and 71% identical to BV-AR02. Notably, ORFV 006/132, 103,
      109, 110, and 116 genes (VEGF, homologues of vaccinia virus A26L, A33R, and A34R,
      and a novel PPV ORF) show an unusual degree of intraspecies variability. These
      genomic differences are consistent with the classification of BPSV and ORFV as
      two PPV species. Compared to other mammalian chordopoxviruses, PPV shares unique
      genomic features with molluscum contagiosum virus, including a G+C-rich
      nucleotide composition, three orthologous genes, and a paucity of nucleotide
      metabolism genes. Together, these data provide a comparative view of PPV
      genomics.

PMID- 14671100
TI  - Control of heterologous hepatitis C virus infection in chimpanzees is associated
      with the quality of vaccine-induced peripheral T-helper immune response.
AB  - Prophylactic hepatitis C virus (HCV) vaccine trials with human volunteers are
      pending. There is an important need for immunological end points which correlate
      with vaccine efficacy and which do not involve invasive procedures, such as liver
      biopsies. By using a multicomponent DNA priming-protein boosting vaccine
      strategy, naive chimpanzees were immunized against HCV structural proteins (core,
      E1, and E2) as well as a nonstructural (NS3) protein. Following immunization,
      exposure to the heterologous HCV 1b J4 subtype resulted in a peak of plasma
      viremia which was lower in both immunized animals. Compared to the naive
      infection control and nine additional historical controls which became chronic,
      vaccinee 2 (Vac2) rapidly resolved the infection, while the other (Vac1) clearly
      controlled HCV infection. Immunization induced antibodies, peptide-specific gamma
      interferon (IFN-gamma), protein-specific lymphoproliferative responses, IFN
      gamma, interleukin-2 (IL-2), and IL-4 T-helper responses in both vaccinees.
      However, the specificities were markedly different: Vac2 developed responses
      which were lower in magnitude than those of Vac1 but which were biased towards
      Th1-type cytokine responses for E1 and NS3. This proof-of-principle study in
      chimpanzees revealed that immunization with a combination of nonstructural and
      structural antigens elicited T-cell responses associated with an alteration of
      the course of infection. Our findings provide data to support the concept that
      the quality of the response to conserved epitopes and the specific nature of the
      peripheral T-helper immune response are likely pivotal factors influencing the
      control and clearance of HCV infection.

PMID- 14671101
TI  - Evasion of cellular antiviral responses by human cytomegalovirus TRS1 and IRS1.
AB  - During infection with human cytomegalovirus (HCMV), cellular protein synthesis
      continues even as viral proteins are being synthesized in abundance. Thus, HCMV
      may have a mechanism for counteracting host cell antiviral pathways that act by
      shutting off translation. Consistent with this view, HCMV infection of human
      fibroblasts rescues the replication of a vaccinia virus mutant lacking the double
      stranded RNA-binding protein gene E3L (VVdeltaE3L). HCMV also prevents the
      phosphorylation of the eukaryotic translation initiation factor eIF-2alpha, the
      activation of RNase L, and the shutoff of viral and cellular protein synthesis
      that otherwise result from VVdeltaE3L infection. To identify the HCMV gene(s)
      responsible for these effects, we prepared a library of VVdeltaE3L recombinants
      containing HCMV genomic fragments. By infecting nonpermissive cells with this
      library and screening for VV gene expression and replication, we isolated a virus
      containing a 2.8-kb HCMV fragment that rescues replication of VVdeltaE3L. The
      fragment comprises the 3' end of the J1S open reading frame through the entire
      TRS1 gene. Analyses of additional VVdeltaE3L recombinants revealed that the
      protein encoded by TRS1, pTRS1, as well as the closely related IRS1 gene, rescues
      VVdeltaE3L replication and prevent the shutoff of protein synthesis, the
      phosphorylation of eIF-2alpha, and activation of RNase L. These results
      demonstrate that TRS1 and IRS1 are able to counteract critical host cell
      antiviral response pathways.

PMID- 14671102
TI  - Subsets of memory cytotoxic T lymphocytes elicited by vaccination influence the
      efficiency of secondary expansion in vivo.
AB  - Vaccine-elicited cytotoxic T lymphocytes (CTL) should be long-lived memory cells
      that can rapidly expand in number following re-exposure to antigen. The present
      studies were initiated to analyze the ability of plasmid interleukin-12 (IL-12)
      to augment CTL responses in mice when delivered during the peak phase of an
      immune response elicited by a plasmid human immunodeficiency virus type 1 gp120
      DNA vaccine. Delivery of plasmid IL-12 on day 10 postimmunization resulted in a
      robust expansion of gp120-specific CD8+ T cells, as measured by tetramer, gamma
      interferon ELISPOT, and functional-killing assays. Interestingly, this delayed
      administration of plasmid IL-12 had no significant effect on antigen-specific
      CD4(+)-T-cell and antibody responses. Phenotypic analyses suggested that
      administration of plasmid IL-12 near the time of the peak CTL response activated
      and expanded antigen-specific effector cells, preventing their loss through
      apoptosis. However, this IL-12-augmented population of gp120-specific CD8+ T
      cells did not efficiently expand following gp120 boost immunization, suggesting
      that these effector cells would be of little utility in expanding to contain a
      viral infection. Analyses of the phenotypic profile and anatomic distribution of
      the plasmid IL-12-augmented CTL population indicated that these lymphocytes were
      primarily effector memory rather than central memory T cells. These observations
      suggest that CTL-based vaccines should elicit central memory rather than effector
      memory T cells and illustrate the importance of monitoring the phenotype and
      functionality of vaccine-induced, antigen-specific CTL.

PMID- 14671103
TI  - N-terminal domain of the murine coronavirus receptor CEACAM1 is responsible for
      fusogenic activation and conformational changes of the spike protein.
AB  - The mouse hepatitis virus (MHV) receptor (MHVR), CEACAM1, has two different
      functions for MHV entry into cells: binding to MHV spike protein (S protein) and
      activation of the S protein to execute virus-cell membrane fusion, the latter of
      which is accompanied by conformational changes of the S protein. The MHVR
      comprising the N-terminal and fourth domains [R1(1,4)] displays these two
      activities, and the N domain is thought to be critical for binding to MHV. In
      this study, we have addressed whether or not the N domain alone is sufficient for
      these activities. We examined three types of soluble form MHVR (soMHVR), one
      consisting of the N domain alone [soR1(1)], one with the N and second domains
      [soR1(1,2)], and one [soR1(1,4)] expressed by recombinant baculoviruses. We
      assessed the abilities of these three types of soMHVR to bind to MHV, activate
      fusogenicity, and induce conformational changes of the S protein. All three types
      of soMHVR similarly bound to MHV, as examined by a solid-phase binding assay and
      neutralized MHV infectivity. They also activated S protein fusogenicity and
      induced its conformational changes with similar levels of efficiency. However,
      R1(1) expressed on the BHK cell surface failed to serve as a receptor in spite of
      a sufficient level of expression. The inability of expressed R1(1) to work as a
      receptor was due to the inaccessibility of virions to R1(1); however, these were
      accessible using the MHVR-specific monoclonal antibody CC1. These results
      collectively indicated that the N domain retains all biological activities
      necessary for receptor function.

PMID- 14671104
TI  - Herpes simplex virus type 1 immediate-early gene expression is required for the
      induction of apoptosis in human epithelial HEp-2 cells.
AB  - Wild-type herpes simplex virus type 1 (HSV-1) induces apoptosis in human
      epithelial HEp-2 cells, but infected cell proteins produced later in infection
      block the process from killing the cells. Thus, HSV-1 infection in the presence
      of the translational inhibitor cycloheximide (CHX) results in apoptosis. Our
      specific goal was to gain insight as to the viral feature(s) responsible for
      triggering apoptosis during HSV-1 infection. We now report the following. (i) No
      viral protein synthesis or death factor processing was detected after infection
      with HSV-1(HFEMtsB7) at 39.5 degrees C; this mutant virus does not inject its
      virion DNA into the nucleus at this nonpermissive temperature. (ii) No death
      factor processing or apoptotic morphological changes were detected following
      infection with UV-irradiated, replication-defective viruses possessing
      transcriptionally active incoming VP16. (iii) Addition of the transcriptional
      inhibitor actinomycin D prevented death factor processing upon infection with the
      apoptotic, ICP27-deletion virus HSV-1(vBSDelta27). (iv) Apoptotic morphologies
      and death factor processing were not observed following infection with HSV
      1(d109), a green fluorescent protein-expressing recombinant virus possessing
      deletions of all five immediate-early (IE) (or alpha) genes. (v) Finally,
      complete death factor processing was observed upon infection with the VP16
      transactivation domain-mutant HSV-1(V422) in the presence of CHX. Based on these
      findings, we conclude that (vi) the expression of HSV-1 alpha/IE genes is
      required for the viral induction of apoptosis and (vii) the transactivation
      activity of VP16 is not necessary for this induction.

PMID- 14671106
TI  - A JC virus-induced signal is required for infection of glial cells by a clathrin-
      and eps15-dependent pathway.
AB  - Infectious entry of JC virus (JCV) into human glial cells occurs by receptor
      mediated clathrin-dependent endocytosis. In this report we demonstrate that the
      tyrosine kinase inhibitor genistein blocks virus entry and inhibits infection.
      Transient expression of dominant-negative eps15 mutants, including a
      phosphorylation-defective mutant, inhibited both virus entry and infection. We
      also show that the JCV-induced signal activates the mitogen-activated protein
      kinases ERK1 and ERK2. These data demonstrate that JC virus binding to human
      glial cells induces an intracellular signal that is critical for entry and
      infection by a ligand-inducible clathrin-dependent mechanism.

PMID- 14671105
TI  - Structural differences among hemagglutinins of influenza A virus subtypes are
      reflected in their antigenic architecture: analysis of H9 escape mutants.
AB  - We used a panel of monoclonal antibodies to H9 hemagglutinin to select 18 escape
      mutants of mouse-adapted influenza A/Swine/Hong Kong/9/98 (H9N2) virus. Cross
      reactions of the mutants with the antibodies and the sequencing of hemagglutinin
      genes revealed two minimally overlapping epitopes. We mapped the amino acid
      changes to two areas of the recently reported three-dimensional structure of
      A/Swine/Hong Kong/9/98 hemagglutinin. The grouping of the antigenically relevant
      amino acid positions in H9 hemagglutinin differs from the pattern observed in H3
      and H5 hemagglutinins. Several positions in site B of H3 hemagglutinin are
      distributed in two sites of H9 hemagglutinin. Unlike any subtype analyzed so far,
      H9 hemagglutinin does not contain an antigenic site corresponding to site A in H3
      hemagglutinin. Positions 145 and 193 (H3 numbering), which in H3 hemagglutinin
      belong to sites A and B, respectively, are within one site in H9 hemagglutinin.
      This finding is consistent with the peculiarity of the three-dimensional
      structure of the H9 molecule, that is, the absence from H9 hemagglutinin of the
      lateral loop that forms site A in H3 and the equivalent site in H5
      hemagglutinins. The escape mutants analyzed displayed phenotypic variations,
      including decreased virulence for mice and changes in affinity for sialyl
      substrates. Our results demonstrate a correlation between intersubtype
      differences in three-dimensional structure and variations among subtypes in the
      distribution of antigenic areas. Our findings also suggest that covariation and
      pleiotropic effects of antibody-selected mutations may be important in the
      evolution of H9 influenza virus, a possible causative agent of a future pandemic.

PMID- 14671107
TI  - Evidence for an essential catalytic role of the F10 protein kinase in vaccinia
      virus morphogenesis.
AB  - Temperature-sensitive mutants of vaccinia virus, with genetic changes that map to
      the open reading frame encoding the F10 protein kinase, exhibit a defect at an
      early stage of viral morphogenesis. To further study the role of the enzyme, we
      constructed recombinant vaccinia virus vF10V5i, which expresses inducible V5
      epitope-tagged F10 and is dependent on a chemical inducer for plaque formation
      and replication. In the absence of inducer, viral membrane formation was delayed
      and crescents and occasional immature forms were detected only late in infection.
      When the temperature was raised from 37 to 39 degrees C, the block in membrane
      formation persisted throughout the infection. The increased stringency may be
      explained by a mild temperature sensitivity of the wild-type F10 kinase, which
      reduced the activity of the very small amount expressed in the absence of
      inducer, or by the thermolability of an unphosphorylated kinase substrate or
      uncomplexed F10-interacting protein. Further analyses demonstrated that tyrosine
      and threonine phosphorylation of the A17 membrane component was inhibited in the
      absence of inducer. The phosphorylation defect could be overcome by transfection
      of plasmids that express wild-type F10, but not by plasmids that express F10 with
      single amino acid substitutions that abolished catalytic activity. Although the
      mutated forms of F10 were stable and concentrated in viral factories, only the
      wild-type protein complemented the assembly and replication defects of vF10V5i in
      the absence of inducer. These studies provide evidence for an essential catalytic
      role of the F10 kinase in vaccinia virus morphogenesis.

PMID- 14671108
TI  - Physical and functional interactions between vaccinia virus F10 protein kinase
      and virion assembly proteins A30 and G7.
AB  - An early step in vaccinia virus morphogenesis, the association of crescent
      membranes with electron-dense granular material, is perturbed when expression of
      the viral protein encoded by the A30L or G7L open reading frame is repressed.
      Under these conditions, we found that phosphorylation of the A17 membrane
      protein, which is mediated by the F10 kinase, was severely reduced. Furthermore,
      A30 and G7 stimulated F10-dependent phosphorylation of A17 in the absence of
      other viral late proteins. Evidence for physical interactions between A30, G7,
      and F10 was obtained by their coimmunoprecipitation with antibody against A30 or
      F10. In addition, phosphorylation of A30 was dependent on the F10 kinase and
      autophosphorylation of F10 was stimulated by A30 and G7. Nevertheless, the
      association of A30, G7, and F10 occurred even with mutated, catalytically
      inactive forms of F10. Just as A30 and G7 are mutually dependent on each other
      for stability, F10 was nearly undetectable in the absence of A30 and G7. The
      reverse is not true, however, as repression of F10 did not diminish A30 or G7.
      Interaction of F10 with A30 and G7 presumably occurred within the virus factory
      areas of the cytoplasm, where each was concentrated. F10 localized predominantly
      in the cortical region of immature virions, beneath the membrane where A17 is
      located. F10 remained associated with the particulate core fraction of mature
      virions after treatment with a nonionic detergent and reducing agent. The
      formation of protein complexes such as the one involving A30, G7, and F10 may be
      a mechanism for the regulated packaging and processing of virion components.

PMID- 14671109
TI  - Immune failure in the absence of profound CD4+ T-lymphocyte depletion in simian
      immunodeficiency virus-infected rapid progressor macaques.
AB  - A fraction of simian immunodeficiency virus (SIV)-infected macaques develop
      rapidly progressive disease in the apparent absence of detectable SIV-specific
      antibody responses. To characterize the immunopathogenesis of this syndrome, we
      studied viral load, CD4+ T-lymphocyte numbers as well as cellular and humoral
      immune responses to SIV and other exogenous antigens in four SIVsm-infected
      rhesus macaques that progressed to AIDS 9 to 16 weeks postinoculation. Each of
      these animals exhibited high levels of viremia but showed relatively preserved
      CD4 T lymphocytes in blood and lymphoid tissues at the time of death. Transient
      SIV-specific antibody responses and cytotoxic T-lymphocyte responses were
      observed at 2 to 4 weeks postinoculation. Two of the macaques that were immunized
      sequentially with tetanus toxoid and hepatitis A virus failed to develop antibody
      to either antigen. These studies show that the SIV-infected rapid progressor
      macaques initially mounted an appropriate but transient cellular and humoral
      immune response. The subsequent immune defect in these animals appeared to be
      global, affecting both cellular and humoral immunity to SIV as well as immune
      responses against unrelated antigens. The lack of CD4 depletion and loss of
      humoral and cellular immune responses suggest that their immune defect may be due
      to an early loss in T helper function.

PMID- 14671110
TI  - Phosphorylation of human cytomegalovirus glycoprotein B (gB) at the acidic
      cluster casein kinase 2 site (Ser900) is required for localization of gB to the
      trans-Golgi network and efficient virus replication.
AB  - Human cytomegalovirus (HCMV) glycoprotein B (gB), encoded by the UL55 open
      reading frame, is an essential envelope glycoprotein involved in cell attachment
      and entry. Previously, we identified residue serine 900 (Ser900) as a unique site
      of reversible casein kinase 2 phosphorylation in the cytoplasmic domain of HCMV
      gB. We have also recently shown that gB is localized to the trans-Golgi network
      (TGN) in HCMV-permissive cells, thereby identifying the TGN as a possible site of
      virus envelopment. The aim of the current study was to determine the role of
      Ser900 phosphorylation in transport of gB to the TGN and in HCMV biogenesis.
      Recombinant HCMV strains were constructed that expressed gB molecules containing
      either an aspartic acid (gBAsp900) or alanine residue (gBAla900) substitution at
      Ser900 to mimic the phosphorylated or nonphosphorylated form, respectively.
      Immunofluorescence analysis of the trafficking of gB mutant molecules in
      fibroblasts infected with the HCMV recombinants revealed that gBAsp900 was
      localized to the TGN. In contrast, gBAla900 was partially mislocalized from the
      TGN, indicating that phosphorylation of gB at Ser900 was necessary for TGN
      localization. The increased TGN localization of gBAsp900 was due to a decreased
      transport of the molecule to post-TGN compartments. Remarkably, the substitution
      of an aspartic acid residue for Ser900 also resulted in an increase in levels of
      progeny virus production during HCMV infection of fibroblasts. Together, these
      results demonstrate that phosphorylation of gB at Ser900 is necessary for gB
      localization to the TGN, as well as for efficient viral replication, and further
      support the TGN as a site of HCMV envelopment.

PMID- 14671111
TI  - The Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1
      N terminus is essential for chromosome association, DNA replication, and episome
      persistence.
AB  - To persist in latently infected, proliferating cells, Kaposi's sarcoma-associated
      herpesvirus (KSHV) episomes must replicate and efficiently segregate to progeny
      nuclei. Episome persistence in uninfected cells requires latency-associated
      nuclear antigen 1 (LANA1) in trans and cis-acting KSHV terminal repeat (TR) DNA.
      The LANA1 C terminus binds TR DNA, and LANA1 mediates TR-associated DNA
      replication in transient assays. LANA1 also concentrates at sites of KSHV TR DNA
      episomes along mitotic chromosomes, consistent with a tethering role to
      efficiently segregate episomes to progeny nuclei. LANA1 amino acids 5 to 22
      constitute a chromosome association region (Piolot et al., J. Virol. 75:3948
      3959, 2001). We now investigate LANA1 residues 5 to 22 with scanning alanine
      substitutions. Mutations targeting LANA1 5GMR7, 8LRS10, and 11GRS13 eliminated
      chromosome association, DNA replication, and episome persistence. LANA1 mutated
      at 14TG15 retained the ability to associate with chromosomes but was partially
      deficient in DNA replication and episome persistence. These results provide
      genetic support for a key role of the LANA1 N terminus in chromosome association,
      LANA1-mediated DNA replication, and episome persistence.

PMID- 14671112
TI  - Selectively receptor-blind measles viruses: Identification of residues necessary
      for SLAM- or CD46-induced fusion and their localization on a new hemagglutinin
      structural model.
AB  - Measles virus (MV) enters cells either through the signaling lymphocyte
      activation molecule SLAM (CD150) expressed only in immune cells or through the
      ubiquitously expressed regulator of complement activation, CD46. To identify
      residues on the attachment protein hemagglutinin (H) essential for fusion support
      through either receptor, we devised a strategy based on analysis of morbillivirus
      H-protein sequences, iterative cycles of mutant protein production followed by
      receptor-based functional assays, and a novel MV H three-dimensional model. This
      model uses the Newcastle disease virus hemagglutinin-neuraminidase protein
      structure as a template. We identified seven amino acids important for SLAM- and
      nine for CD46 (Vero cell receptor)-induced fusion. The MV H three-dimensional
      model suggests (i) that SLAM- and CD46-relevant residues are located in
      contiguous areas in propeller beta-sheets 5 and 4, respectively; (ii) that two
      clusters of SLAM-relevant residues exist and that they are accessible for
      receptor contact; and (iii) that several CD46-relevant amino acids may be
      shielded from direct receptor contacts. It appears likely that certain residues
      support receptor-specific H-protein conformational changes. To verify the
      importance of the H residues identified with the cell-cell fusion assays for
      virus entry into cells, we transferred the relevant mutations into genomic MV
      cDNAs. Indeed, we were able to recover recombinant viruses, and we showed that
      these replicate selectively in cells expressing SLAM or CD46. Selectively
      receptor-blind viruses will be used to study MV pathogenesis and may have
      applications for the production of novel vaccines and therapeutics.

PMID- 14671113
TI  - Genotyping of porcine endogenous retroviruses from a family of miniature swine.
AB  - The identification of animals in an inbred miniature swine herd that consistently
      fail to produce replication- competent humantropic porcine endogenous retrovirus
      (PERV) has prompted studies on the biology of PERV in transmitter and
      nontransmitter animals. We analyzed PERV RNA transcript profiles in a family of
      inbred miniature swine (SLA(d/d) haplotype) in which individual members differed
      in their capacity to generate humantropic and ecotropic (i.e., pigtropic) virus.
      We identified unique HaeIII and HpaII gag restriction fragment length
      polymorphism (RFLP) profiles resulting from single nucleotide polymorphisms in
      blood cells; these were found only in animals that produced humantropic PERV.
      These HaeIII and HpaII gag RFLP profiles proved to be components of humantropic
      PERV as they were transmitted to 293 human target cells in vitro. The humantropic
      HaeIII and HpaII gag RFLP genotypes in the family of study were not present in
      other miniature swine in the herd that produced humantropic PERV, indicating that
      these RFLP profiles relate specifically to this family's lineage.

PMID- 14671114
TI  - The ORF2 protein of hepatitis E virus binds the 5' region of viral RNA.
AB  - Hepatitis E virus (HEV) is a major human pathogen in much of the developing
      world. It is a plus-strand RNA virus with a 7.2-kb polyadenylated genome
      consisting of three open reading frames, ORF1, ORF2, and ORF3. Of these, ORF2
      encodes the major capsid protein of the virus and ORF3 encodes a small protein of
      unknown function. Using the yeast three-hybrid system and traditional biochemical
      techniques, we have studied the RNA binding activities of ORF2 and ORF3, two
      proteins encoded in the 3' structural part of the genome. Since the genomic RNA
      from HEV has been postulated to contain secondary structures at the 5' and 3'
      ends, we used these two terminal regions, besides other regions within the
      genome, in this study. Experiments were designed to test for interactions between
      the genomic RNA fusion constructs with ORF2 and ORF3 hybrid proteins in a yeast
      cellular environment. We show here that the ORF2 protein contains RNA binding
      activity. The ORF2 protein specifically bound the 5' end of the HEV genome.
      Deletion analysis of this protein showed that its RNA binding activity was lost
      when deletions were made beyond the N-terminal 111 amino acids. Finer mapping of
      the interacting RNA revealed that a 76-nucleotide (nt) region at the 5' end of
      the HEV genome was responsible for binding the ORF2 protein. This 76-nt region
      included the 51-nt HEV sequence, conserved across alphaviruses. Our results
      support the requirement of this conserved sequence for interaction with ORF2 and
      also indicate an increase in the strength of the RNA-protein interaction when an
      additional 44 bases downstream of this 76-nt region were included. Secondary
      structure predictions and the location of the ORF2 binding region within the HEV
      genome indicate that this interaction may play a role in viral encapsidation.

PMID- 14671115
TI  - Characterization of the interaction between P143 and LEF-3 from two different
      baculovirus species: Choristoneura fumiferana nucleopolyhedrovirus LEF-3 can
      complement Autographa californica nucleopolyhedrovirus LEF-3 in supporting DNA
      replication.
AB  - The baculovirus protein P143 is essential for viral DNA replication in vivo,
      likely as a DNA helicase. We have demonstrated that another viral protein, LEF-3,
      first described as a single-stranded DNA binding protein, is required for
      transporting P143 into the nuclei of insect cells. Both of these proteins, along
      with several other early viral proteins, are also essential for DNA replication
      in transient assays. We now describe the identification, nucleotide sequences,
      and transcription patterns of the Choristoneura fumiferana nucleopolyhedrovirus
      (CfMNPV) homologues of p143 and lef-3 and demonstrate that CfMNPV LEF-3 is also
      responsible for P143 localization to the nucleus. We predicted that the
      interaction between P143 and LEF-3 might be critical for cross-species
      complementation of DNA replication. Support for this hypothesis was generated by
      substitution of heterologous P143 and LEF-3 between two different baculovirus
      species, Autographa californica nucleopolyhedrovirus and CfMNPV, in transient DNA
      replication assays. The results suggest that the P143-LEF-3 complex is an
      important baculovirus replication factor.

PMID- 14671116
TI  - Functional analysis of Epstein-Barr virus SM protein: identification of amino
      acids essential for structure, transactivation, splicing inhibition, and virion
      production.
AB  - The Epstein-Barr virus (EBV) SM protein is a posttranscriptional regulator of
      cellular and viral gene expression that binds and stabilizes target mRNAs and
      shuttles from nucleus to cytoplasm. SM enhances expression of several EBV genes
      required for lytic replication and is essential for virion production. SM
      increases accumulation of specific mRNAs but also inhibits expression of several
      intron-containing transcripts. The mechanism by which SM inhibits gene expression
      is poorly understood. The experiments described here had several aims: to
      determine whether specific domains of SM were responsible for activation or
      inhibition function; whether these functions could be separated; and whether one
      or more of these functions were essential for virion production. A mutational
      analysis of SM was performed, focusing on amino acids in SM that are
      evolutionarily conserved among SM homologs in other herpesviruses. Mutation of
      the carboxy-terminal region of SM revealed a region that is likely to be
      structurally important for SM protein conformation. In addition, several amino
      acids were identified that are critical for activation and inhibition function. A
      specific mutation of a highly conserved cysteine residue revealed that it was
      essential for gene inhibition but not for transactivation, indicating that these
      two functions operate through independent mechanisms. Furthermore, the ability of
      wild-type SM and the inability of the mutant to inhibit gene expression were
      shown to correlate with the ability to inhibit splicing of a human target gene
      and thereby prevent accumulation of its processed mRNA. Surprisingly, some
      mutations which preserved both activation and inhibition functions in vitro
      nevertheless abolished virion production, suggesting that other SM functions or
      protein-protein interactions are also required for lytic replication.

PMID- 14671117
TI  - The genome of canarypox virus.
AB  - Here we present the genomic sequence, with analysis, of a canarypox virus (CNPV).
      The 365-kbp CNPV genome contains 328 potential genes in a central region and in
      6.5-kbp inverted terminal repeats. Comparison with the previously characterized
      fowlpox virus (FWPV) genome revealed avipoxvirus-specific genomic features,
      including large genomic rearrangements relative to other chordopoxviruses and
      novel cellular homologues and gene families. CNPV also contains many genomic
      differences with FWPV, including over 75 kbp of additional sequence, 39 genes
      lacking FWPV homologues, and an average of 47% amino acid divergence between
      homologues. Differences occur primarily in terminal and, notably, localized
      internal genomic regions and suggest significant genomic diversity among
      avipoxviruses. Divergent regions contain gene families, which overall comprise
      over 49% of the CNPV genome and include genes encoding 51 proteins containing
      ankyrin repeats, 26 N1R/p28-like proteins, and potential immunomodulatory
      proteins, including those similar to transforming growth factor beta and beta
      nerve growth factor. CNPV genes lacking homologues in FWPV encode proteins
      similar to ubiquitin, interleukin-10-like proteins, tumor necrosis factor
      receptor, PIR1 RNA phosphatase, thioredoxin binding protein, MyD116 domain
      proteins, circovirus Rep proteins, and the nucleotide metabolism proteins
      thymidylate kinase and ribonucleotide reductase small subunit. These data reveal
      genomic differences likely affecting differences in avipoxvirus virulence and
      host range, and they will likely be useful for the design of improved vaccine
      vectors.

PMID- 14671118
TI  - EBNA3C coactivation with EBNA2 requires a SUMO homology domain.
AB  - Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) is critical for EBV
      immortalization of infected B lymphocytes and can coactivate the EBV LMP1
      promoter with EBNA2. EBNA3C amino acids 365 to 545 are necessary and sufficient
      for coactivation and are required for SUMO-1 and SUMO-3 interaction. We found
      that EBNA3C but not EBNA3CDelta343-545 colocalized with SUMO-1 in nuclear bodies
      and was modified by SUMO-2, SUMO-3, and SUMO-1. EBNA3C amino acids 545 to 628 and
      amino acids 30 to 365 were also required for EBNA3C sumolation and nuclear body
      localization but were dispensable for coactivation, indicating that EBNA3C
      sumolation is not required for coactivation. Furthermore, EBNA3C amino acids 476
      to 992 potently coactivated with EBNA2 but EBNA3C amino acids 516 to 922 lacked
      activity, indicating that amino acids 476 to 515 are critical for coactivation.
      EBNA3C amino acids 476 to 515 include DDDVIEV(507-513), which are similar to SUMO
      1 EEDVIEV(84-90). EBNA3C m1 and m2 point mutations, DDD(507-509) mutated to AAA
      and DVIEVID(509-513) mutated to AVIAVIA, respectively, diminished SUMO-1 and SUMO
      3 interaction in directed yeast two-hybrid and glutathione S-transferase pulldown
      assays. Furthermore, EBNA3C m1 and m2 did not coactivate the LMP1 promoter with
      EBNA2. Overexpression of wild-type SUMO-1, SUMO-3, and the SUMO-conjugating
      enzyme UBC9 coactivated the LMP1 promoter with EBNA2. Since EBNA2 activation is
      dependent on p300/CBP, the possible effect of EBNA3C on p300-mediated
      transcription was assayed. EBNA3C potentiated transcription of p300 fused to a
      heterologous DNA binding domain, whereas EBNA3C m1 and m2 did not. All of these
      data are consistent with a model in which EBNA3C upregulates EBNA2-mediated gene
      activation by binding to a sumolated repressor and inhibiting repressive effects
      on p300/CBP and other transcription factor(s) at EBNA2-regulated promoters.

PMID- 14671119
TI  - An external loop region of domain III of dengue virus type 2 envelope protein is
      involved in serotype-specific binding to mosquito but not mammalian cells.
AB  - Dengue virus (DV) is a flavivirus and infects mammalian cells through mosquito
      vectors. This study investigates the roles of domain III of DV type 2 envelope
      protein (EIII) in DV binding to the host cell. Recombinant EIII interferes with
      DV infection to BHK21 and C6/36 cells by blocking dengue virion adsorption to
      these cells. Inhibition of EIII on BHK21 cells was broad with no serotype
      specificity; however, inhibition of EIII on C6/36 cells was relatively serotype
      specific. Soluble heparin completely blocks binding of EIII to BHK21 cells,
      suggesting that domain III binds mainly to cell surface heparan sulfates. This
      suggestion is supported by the observation that EIII binds very weakly to gro2C
      and sog9 mutant mammalian cell lines that lack heparan sulfate. In contrast,
      heparin does not block binding of EIII to mosquito cells. Furthermore, a
      synthetic peptide that includes amino acids (aa) 380 to 389 of EIII, IGVEPGQLKL,
      inhibits binding of EIII to C6/36 but not BHK21 cells. This peptide corresponds
      to a lateral loop region on domain III of E protein, indicating a possible role
      of this loop in binding to mosquito cells. In summary, these results suggest that
      EIII plays an important role in binding of DV type 2 to host cells. In addition,
      EIII interacts with heparan sulfates when binding to BHK21 cells, and a loop
      region containing aa 380 to 389 of EIII may participate in DV type 2 binding to
      C6/36 cells.

PMID- 14671121
TI  - Herpes simplex virus type 1 primary envelopment: UL34 protein modification and
      the US3-UL34 catalytic relationship.
AB  - The herpes simplex virus type 1 (HSV-1) US3 kinase is likely important for
      primary envelopment of progeny nucleocapsids since it localizes to the nuclear
      envelope of infected cells and largely determines the phosphorylation state and
      localization of the necessary primary envelopment factor, the UL34 protein. In
      HEp-2 cells, the production of infectious US3 null progeny is delayed and
      decreased relative to that of the parental strain, HSV-1(F). Furthermore, the US3
      kinase affects the morphology of primary envelopment such that in its absence,
      UL34 protein-containing enveloped virions accumulate within membrane-bound
      vesicles. These vesicles are most often found along the interior periphery of the
      nucleus and may be derived from the inner nuclear membrane. Since the US3 and
      UL34 proteins comprise a kinase-substrate pair, a reasonable hypothesis is that
      the US3 kinase influences these replication parameters by direct phosphorylation
      of the UL34 protein. For this report, recombinant viruses were constructed to
      determine the significance of UL34 protein phosphorylation and US3 catalytic
      activity on UL34 protein localization, single-step growth, and envelopment
      morphology in both HEp-2 and Vero cells. The data presented suggest that the
      significance of UL34 phosphorylation is cell type dependent and that efficient
      viral morphogenesis requires US3-mediated phosphorylation of an infected cell
      protein other than UL34.

PMID- 14671120
TI  - Spatial and temporal organization of adeno-associated virus DNA replication in
      live cells.
AB  - Upon cell entry, the genomes of herpes simplex virus type 1 (HSV-1) and
      adenovirus (Ad) associate with distinct nuclear structures termed ND10 or
      promyelocytic leukemia (PML) nuclear bodies (NBs). PML NB morphology is altered
      or disrupted by specific viral proteins as replication proceeds. We examined
      whether adeno-associated virus (AAV) replication compartments also associate with
      PML NBs, and whether modification or disruption of these by HSV-1 or Ad, both of
      which are helper viruses for AAV, is necessary at all. Furthermore, to add a
      fourth dimension to our present view of AAV replication, we established an assay
      that allows visualization of AAV replication in live cells. A recombinant AAV
      containing 40 lac repressor binding sites between the AAV inverted terminal
      repeats was constructed. AAV Rep protein and helper virus-mediated replication of
      this recombinant AAV genome was visualized by binding of enhanced yellow
      fluorescent protein-lac repressor fusion protein to double-stranded AAV
      replication intermediates. We demonstrate in live cells that AAV DNA replication
      occurs in compartments which colocalize with AAV Rep. Early after infection, the
      replication compartments were small and varied in numbers from 2 to more than 40
      per cell nucleus. Within 4 to 8 h, individual small replication compartments
      expanded and fused to larger structures which filled out much of the cell
      nucleus. We also show that AAV replication compartments can associate with
      modified PML NBs in Ad-infected cells. In wild-type HSV-1-infected cells, AAV
      replication compartments and PML NBs did not coexist, presumably because PML was
      completely disrupted by the HSV-1 ICP0 protein. However, alteration or disruption
      of PML appears not to be a prerequisite for AAV replication, as the formation of
      replication compartments was normal when the ICP0 mutants HSV-1 dl1403 and HSV-1
      FXE, which do not affect PML NBs, were used as the helper viruses; under these
      conditions, AAV replication compartments did not associate with PML NBs.

PMID- 14671122
TI  - Structural and functional analysis of human cytomegalovirus US3 protein.
AB  - Human cytomegalovirus (HCMV) unique short region 3 (US3) protein, a type I
      membrane protein, prevents maturation of class I major histocompatibility complex
      (MHC) molecules by retaining them in the endoplasmic reticulum (ER) and thus
      helps inhibit antigen presentation to cytotoxic T cells. US3 molecules bind to
      class I MHC molecules in a transient fashion but retain them very efficiently in
      the ER nonetheless. The US3 luminal domain is responsible for ER retention of US3
      itself, while both the US3 luminal and transmembrane domains are necessary for
      retaining class I MHC in the ER. We have expressed the luminal domain of US3
      molecule in Escherichia coli and analyzed its secondary structure by using
      nuclear magnetic resonance. We then predicted the US3 tertiary structure by
      modeling it based on the US2 structure. Unlike the luminal domain of US2, the US3
      luminal domain does not obviously interact with class I MHC molecules. The
      luminal domain of US3 dynamically oligomerizes in vitro and full-length US3
      molecules associate with each other in vivo. We present a model depicting how
      dynamic oligomerization of US3 may enhance its ability to retain class I
      molecules within the ER.

PMID- 14671123
TI  - Complete, annotated sequence of the pseudorabies virus genome.
AB  - We have obtained the complete DNA sequence of pseudorabies virus (PRV), an
      alphaherpesvirus also known as Aujeszky's disease virus or suid herpesvirus 1,
      using sequence fragments derived from six different strains (Kaplan, Becker,
      Rice, Indiana-Funkhauser, NIA-3, and TNL). The assembled PRV genome sequence
      comprises 143,461 nucleotides. As expected, it matches the predicted gene
      arrangement, genome size, and restriction enzyme digest patterns. More than 70
      open reading frames were identified with homologs in related alphaherpesviruses;
      none were unique to PRV. RNA polymerase II transcriptional control elements in
      the PRV genome, including core promoters, splice sites, and polyadenylation
      sites, were identified with computer prediction programs. The correlation between
      predicted and experimentally determined transcription start and stop sites was
      excellent. The transcriptional control architecture is characterized by three key
      features: core transcription elements shared between genes, yielding divergent
      transcripts and a large number of coterminal transcripts; bifunctional
      transcriptional elements, yielding head-to-tail transcripts; and short repetitive
      sequences that could function as insulators against improperly terminated
      transcripts. Many of these features are conserved in the alphaherpesvirus
      subfamily and have important implications for gene array analyses.

PMID- 14671124
TI  - The Rep protein of adeno-associated virus type 2 interacts with single-stranded
      DNA-binding proteins that enhance viral replication.
AB  - Adeno-associated virus (AAV) type 2 is a human parvovirus whose replication is
      dependent upon cellular proteins as well as functions supplied by helper viruses.
      The minimal herpes simplex virus type 1 (HSV-1) proteins that support AAV
      replication in cell culture are the helicase-primase complex of UL5, UL8, and
      UL52, together with the UL29 gene product ICP8. We show that AAV and HSV-1
      replication proteins colocalize at discrete intranuclear sites. Transfections
      with mutant genes demonstrate that enzymatic functions of the helicase-primase
      are not essential. The ICP8 protein alone enhances AAV replication in an in vitro
      assay. We also show localization of the cellular replication protein A (RPA) at
      AAV centers under a variety of conditions that support replication. In vitro
      assays demonstrate that the AAV Rep68 and Rep78 proteins interact with the single
      stranded DNA-binding proteins (ssDBPs) of Ad (Ad-DBP), HSV-1 (ICP8), and the cell
      (RPA) and that these proteins enhance binding and nicking of Rep proteins at the
      origin. These results highlight the importance of intranuclear localization and
      suggest that Rep interaction with multiple ssDBPs allows AAV to replicate under a
      diverse set of conditions.

PMID- 14671125
TI  - The adenovirus E3-6.7K protein adopts diverse membrane topologies following
      posttranslational translocation.
AB  - The E3 region of adenovirus codes for several membrane proteins, most of which
      are involved in immune evasion and prevention of host cell apoptosis. We explored
      the topology and targeting mechanisms of E3-6.7K, the most recently described
      member of this group, by using an in vitro translation system supplemented with
      microsomes. Here, we present evidence that E3-6.7K, one of the smallest signal
      anchor proteins known, translocates across the membrane of the endoplasmic
      reticulum in a posttranslational, ribosome-independent, yet ATP-dependent manner,
      reminiscent of the translocation of tail-anchored proteins. Our analysis also
      demonstrated that E3-6.7K could achieve several distinct topological fates. In
      addition to the previously postulated type III orientation (N-luminal/C
      cytoplasmic, termed NtmE3-6.7K), we detected a tail-anchored form adopting the
      opposite orientation (N-cytoplasmic/C-luminal, termed CtmE3-6.7K) as well as the
      possibility of a fully translocated form (N and C termini are both translocated,
      termed NCE3-6.7K). Due to the translocation of a positively charged domain, both
      the CtmE3-6.7K and NCE3-6.7K topologies of E3-6.7K constitute exceptions to the
      "positive inside" rule. The NtmE3-6.7K and NCE3-6.7K are the first examples of
      posttranslationally translocated proteins in higher eukaryotes that are not tail
      anchored. Distinct topological forms were also found in transfected cells, as
      both N and C termini of E3-6.7K were detected on the extracellular surface of
      transfected cells. The demonstration of unexpected topological forms and
      translocation mechanisms for E3-6.7K defies conventional thinking about membrane
      protein topogenesis and advises that both the mode of targeting and topology of
      signal-anchor proteins should be determined experimentally.

PMID- 14671126
TI  - Pseudorabies virus UL3 gene codes for a nuclear protein which is dispensable for
      viral replication.
AB  - Many of the products of the ca. 80 genes encoded by alphaherpesviruses have
      already been identified and, at least tentatively, functionally characterized.
      Among the least characterized proteins are the products of the genes homologous
      to herpes simplex virus UL3, which are present only in the subfamily
      Alphaherpesvirinae: To identify the UL3 protein of the porcine alphaherpesvirus
      pseudorabies virus (PrV), the complete PrV UL3 open reading frame was cloned,
      expressed in Escherichia coli as a glutathione S-transferase fusion protein, and
      used for immunization of a rabbit. In Western blots, the generated antiserum
      specifically detected a 34-kDa protein in PrV-infected cells, which was absent
      from purified virus preparations, indicating that PrV UL3 encodes a nonstructural
      protein. In indirect immunofluorescence analysis, the anti-UL3 serum produced
      predominantly nuclear staining in transfected as well as in infected cells, which
      was not altered in the absence of other virus-encoded nuclear proteins such as
      the UL31 and UL34 gene products. To investigate UL3 function, a deletion mutant,
      PrV-DeltaUL3F2, was constructed and characterized. This mutant replicated and
      formed plaques on noncomplementing cells indistinguishable from wild-type PrV,
      demonstrating that PrV UL3 is not required for virus propagation in cultured
      cells. Moreover, ultrastructural examinations revealed no impairment of capsid
      formation in the nucleus, nuclear egress of capsids, virion maturation in the
      cytoplasm, or virus release. Thus, the overall properties of PrV UL3 are similar
      to those described for the homologous herpes simplex virus proteins which may be
      indicative of a common, yet hitherto unknown, function in alphaherpesvirus
      replication. However, based on our studies, an involvement of the UL3 homologs in
      virion formation appears unlikely.

PMID- 14671127
TI  - A point mutation in the binding subunit of a retroviral envelope protein arrests
      virus entry at hemifusion.
AB  - The transmembrane subunits of viral envelope proteins are thought to perform all
      of the functions required for membrane fusion during entry of enveloped viruses.
      However, changes in a conserved SPHQ motif near the N terminus of the receptor
      binding subunit of a murine leukemia virus (MLV) envelope protein block infection
      and induction of cell-cell fusion but not receptor binding. Here we report
      evidence that a histidine-to-arginine change at position 8 (H8R) in the SPHQ
      motif of Moloney MLV blocks infection by arresting virus-cell fusion at the
      hemifusion state. In cell-cell fusion assays, H8R envelope protein induced mixing
      of membrane outer leaflet lipids but did not lead to content mixing, a finding
      indicative of fusion pore formation. Kinetic studies of virus-cell fusion showed
      that lipid mixing of H8R virus membranes begins much later than for wild-type
      virus. The length of the delay in lipid mixing decreased upon addition of two
      second-site changes that increase H8R virus infection to 100-fold less than the
      wild-type virus. Finally, chlorpromazine, dibucaine, and trifluoperazine, agents
      that induce pores in an arrested hemifusion state, rescued infection by H8R virus
      to within 2.5-fold of the level of wild-type virus infection and cell-cell fusion
      to half that mediated by wild-type envelope protein. We interpret these results
      to indicate that fusion progressed to the hemifusion intermediate but fusion pore
      formation was inhibited. These results establish that membrane fusion of Moloney
      MLV occurs via a hemifusion intermediate. We also interpret these findings as
      evidence that histidine 8 is a key switch-point residue between the receptor
      induced conformation changes that expose fusion peptide and those that lead to
      six-helix bundle formation.

PMID- 14671128
TI  - Cultured peripheral neuroglial cells are highly permissive to sheep prion
      infection.
AB  - Transmissible spongiform encephalopathies arise as a consequence of infection of
      the central nervous system (CNS) by prions. Spreading of the infectious agent
      through the peripheral nervous system (PNS) may represent a crucial step toward
      CNS neuroinvasion, but the modalities of this process have yet to be clarified.
      Here we provide further evidence that PNS glial cells are likely targets for
      infection by prions. Glial cell clones originating from dorsal root ganglia of
      transgenic mice expressing ovine PrP (tgOv) and simian virus 40 T antigen were
      found to be readily infectible by sheep scrapie agent. This led us to establish
      two stable cell lines that exhibited features of Schwann cells. These cells were
      shown to sustain an efficient and stable replication of sheep prion based on the
      high level of accumulation of abnormal PrP and infectivity in exposed cultures.
      We also provide evidence for abnormal PrP deposition in peripheral neuroglial
      cells from scrapie-infected tgOv mice and sheep. These findings have potential
      implications in terms of designing new cell systems permissive to prions and of
      peripheral pathobiology of prion infections.

PMID- 14671129
TI  - Hepatitis C virus subgenomic replicons in the human embryonic kidney 293 cell
      line.
AB  - Hepatitis C virus (HCV) infects liver cells and its replication in other cells is
      incompletely defined. Human hepatoma Huh-7 cells harboring subgenomic HCV
      replicons were used in somatic cell fusion experiments with human embryonic
      kidney 293 cells as a means of examining the permissiveness of 293 cells for HCV
      subgenomic RNA replication. 293 cells were generally not permissive for
      replication of Huh-7 cell-adapted replicons. However, upon coculturing of the two
      cell lines, we selected rare replicon-containing cells, termed 293Rep cells, that
      resembled parental 293 cells. Direct metabolic labeling of cells with (33)P in
      the presence of actinomycin D and Northern blotting to detect the negative strand
      of the replicon demonstrated functional RNA replicons in 293Rep cells.
      Furthermore, Western blots revealed that 293Rep cells expressed the HCV
      nonstructural proteins as well as markers of the naive 293 cells but not Huh-7
      cells. Propidium iodide staining and fluorescence-activated cell sorting analysis
      of 293Rep cells revealed that clone 293Rep17 closely resembled naive 293 cells.
      Transfection of total RNA from 293Rep17 into naive 293 cells produced replicon
      containing 293 cell lines with characteristics distinct from those of Huh-7
      derived replicon cell lines. Relative to Huh-7 replicons, the 293 cell replicons
      were less sensitive to inhibition by alpha interferon and substantially more
      sensitive to inhibition by poly(I)-poly(C) double-stranded RNA. This study
      established HCV subgenomic replicons in nonhepatic 293 cells and demonstrated
      their utility in expanding the study of cellular HCV RNA replication.

PMID- 14671130
TI  - Restrictions to the adaptation of influenza a virus h5 hemagglutinin to the human
      host.
AB  - The binding specificities of a panel of avian influenza virus subtype H5
      hemagglutinin (HA) proteins bearing mutations at key residues in the receptor
      binding site were investigated. The results demonstrate that two simultaneous
      mutations in the receptor binding site resulted in H5 HA binding in a pattern
      similar to that shown by human viruses. Coexpression of the ion channel protein,
      M2, from most avian and human strains tested protected H5 HA conformation during
      trafficking, indicating that no genetic barrier to the reassortment of the H5
      surface antigen gene with internal genes of human viruses existed at this level.

PMID- 14671131
TI  - An aromatic side chain is required at residue 8 of SU for fusion of ecotropic
      murine leukemia virus.
AB  - The surface glycoprotein (SU) of most gammaretroviruses contains a conserved
      histidine at its amino terminus. In ecotropic murine leukemia virus SU,
      replacement of histidine 8 with arginine (H8R) or deletion of H8 (H8del)
      abolishes infection and cell-cell fusion but has no effect on binding to the
      cellular receptor. We report here that an aromatic ring side chain is essential
      to the function of residue 8. The size of the aromatic ring appears to be
      important, as does its ability to form a hydrogen bond. In addition, infection by
      all of the nonaromatic amino acid substitutions could be partially rescued by the
      addition of two suppressor mutations (glutamine 227 to arginine [Q227R] and
      aspartate 243 to tyrosine [D243Y]) or by exposure to chlorpromazine, an agent
      that induces fusion pores in hemifusion intermediates to complete fusion,
      suggesting that, like the previously described H8R mutant, the mutants reported
      here also arrest membrane fusion at the hemifusion state. We propose that H8 is a
      key switch-point residue in the conformation changes that lead to membrane fusion
      and present a possible mechanism for how its substitution arrests fusion at the
      hemifusion state.

PMID- 14671132
TI  - Chromosome-protein interactions in polyomavirus virions.
AB  - In this work, we sought to determine whether the components of the murine
      polyomavirus capsid establish specific interactions with the minichromosome
      encapsidated into the mature viral particles by using the cis
      diamminedichloroplatinum(II) cross-linking reagent. Our data indicated that VP1,
      but not minor capsid proteins, interacts with the viral genome in vivo. In
      addition, semiquantitative PCR assays performed on cross-linked DNA complexes
      revealed that VP1 binds to all regions of the viral genome but significantly more
      to the regulatory region. The implications of such an interaction for viral
      infectivity are discussed.

PMID- 14671133
TI  - Failure of thymidine kinase-negative herpes simplex virus to reactivate from
      latency following efficient establishment.
AB  - Thymidine kinase-negative mutants of herpes simplex virus did not reactivate from
      latency in mouse trigeminal ganglia, even when their latent viral loads were
      comparable to those that permitted reactivation by wild-type virus. Thus, reduced
      establishment of latency does not suffice to account for the failure to
      reactivate.

PMID- 14671134
TI  - Intrapatient alterations in the human immunodeficiency virus type 1 gp120 V1V2
      and V3 regions differentially modulate coreceptor usage, virus inhibition by
      CC/CXC chemokines, soluble CD4, and the b12 and 2G12 monoclonal antibodies.
AB  - We studied human immunodeficiency virus type 1 (HIV-1) chimeric viruses altering
      in their gp120 V1V2 and V3 envelope regions to better map which genetic
      alterations are associated with specific virus phenotypes associated with HIV-1
      disease progression. The V1V2 and V3 regions studied were based on viruses
      isolated from an individual with progressing HIV-1 disease. Higher V3 charges
      were linked with CXCR4 usage, but only when considered within a specific V1V2 and
      V3 N-linked glycosylation context. When the virus gained R5X4 dual tropism,
      irrespective of its V3 charge, it became highly resistant to inhibition by RANTES
      and highly sensitive to inhibition by SDF-1alpha. R5 viruses with higher positive
      V3 charges were more sensitive to inhibition by RANTES, while R5X4 dualtropic
      viruses with higher positive V3 charges were more resistant to inhibition by SDF
      1alpha. Loss of the V3 N-linked glycosylation event rendered the virus more
      resistant to inhibition by SDF-1alpha. The same alterations in the V1V2 and V3
      regions influenced the extent to which the viruses were neutralized with soluble
      CD4, as well as monoclonal antibodies b12 and 2G12, but not monoclonal antibody
      2F5. These results further identify a complex set of alterations within the V1V2
      and V3 regions of HIV-1 that can be selected in the host via alterations of
      coreceptor usage, CC/CXC chemokine inhibition, CD4 binding, and antibody
      neutralization.

PMID- 14671135
TI  - Tetracycline-inducible packaging cell line for production of flavivirus replicon
      particles.
AB  - We have previously developed replicon vectors derived from the Australian
      flavivirus Kunjin that have a unique noncytopathic nature and have been shown to
      direct prolonged high-level expression of encoded heterologous genes in vitro and
      in vivo and to induce strong and long-lasting immune responses to encoded
      immunogens in mice. To facilitate further applications of these vectors in the
      form of virus-like particles (VLPs), we have now generated a stable BHK packaging
      cell line, tetKUNCprME, carrying a Kunjin structural gene cassette under the
      control of a tetracycline-inducible promoter. Withdrawal of tetracycline from the
      medium resulted in production of Kunjin structural proteins that were capable of
      packaging transfected and self-amplified Kunjin replicon RNA into the secreted
      VLPs at titers of up to 1.6 x 10(9) VLPs per ml. Furthermore, secreted KUN
      replicon VLPs from tetKUNCprME cells could be harvested continuously for as long
      as 10 days after RNA transfection, producing a total yield of more than 10(10)
      VLPs per 10(6) transfected cells. Passaging of VLPs on Vero cells or
      intracerebral injection into 2- to 4-day-old suckling mice illustrated the
      complete absence of any infectious Kunjin virus. tetKUNCprME cells were also
      capable of packaging replicon RNA from closely and distantly related
      flaviviruses, West Nile virus and dengue virus type 2, respectively. The utility
      of high-titer KUN replicon VLPs was demonstrated by showing increasing CD8(+)-T
      cell responses to encoded foreign protein with increasing doses of KUN VLPs. A
      single dose of 2.5 x 10(7) VLPs carrying the human respiratory syncytial virus M2
      gene induced 1,400 CD8 T cells per 10(6) splenocytes in an ex vivo gamma
      interferon enzyme-linked immunospot assay. The packaging cell line thus
      represents a significant advance in the development of the noncytopathic Kunjin
      virus replicon-based gene expression system and may be widely applicable to the
      basic studies of flavivirus RNA packaging and virus assembly as well as to the
      development of gene expression systems based on replicons from different
      flaviviruses.

PMID- 14671136
TI  - Rapid genetic engineering of human cytomegalovirus by using a lambda phage linear
      recombination system: demonstration that pp28 (UL99) is essential for production
      of infectious virus.
AB  - A highly efficient lambda phage recombination system previously utilized for
      studies of bacterial artificial chromosome (BAC)-maintained mouse chromosomal DNA
      was adapted for the study of the role of human cytomegalovirus (HCMV)-encoded
      pp28 (UL99) in virus replication. Incorporating a two-step mutagenesis strategy
      with blue/white selection in Escherichia coli containing a HCMV AD169 BAC, we
      have shown that we can rapidly introduce point mutations into the HCMV BAC using
      linear PCR fragments. All manipulations were carried out in bacteria, which
      greatly accelerated the introduction and analysis of mutations in the viral
      genome. Our results indicated that HCMV pp28 was essential for the production of
      infectious virus and that introduction of a single base change that resulted in
      loss of the myristylation site on pp28 was also associated with the lack of
      production of infectious virus. Although the block in the viral morphogenesis
      cannot be determined from these studies, the latter finding suggested that
      authentic intracellular localization of pp28, not only the expression of the
      protein, is required for virus assembly.

PMID- 14671137
TI  - Epstein-Barr virus immediate-early protein BZLF1 inhibits tumor necrosis factor
      alpha-induced signaling and apoptosis by downregulating tumor necrosis factor
      receptor 1.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a key mediator of host immune and
      inflammatory responses and inhibits herpesvirus replication by cytolytic and
      noncytolytic mechanisms. TNF-alpha effects are primarily mediated through the
      major TNF-alpha receptor, TNF-R1, which is constitutively expressed in most cell
      types. Here we show that the Epstein-Barr virus (EBV) immediate-early protein
      BZLF1 prevents TNF-alpha activation of target genes and TNF-alpha-induced cell
      death. These effects are mediated by down-regulation of the promoter for TNF-R1.
      Additionally, we demonstrate that expression of TNF-R1 is downregulated during
      the EBV lytic replication cycle. Thus, EBV has developed a novel mechanism for
      evading TNF-alpha antiviral effects during lytic reactivation or primary
      infection.

PMID- 14671138
TI  - Diagnosis and complications of Cushing's syndrome: a consensus statement.
AB  - In October 2002, a workshop was held in Ancona, Italy, to reach a Consensus on
      the management of Cushing's syndrome. The workshop was organized by the
      University of Ancona and sponsored by the Pituitary Society, the European
      Neuroendocrine Association, and the Italian Society of Endocrinology. Invited
      international participants included almost 50 leading endocrinologists with
      specific expertise in the management of Cushing's syndrome. The consensus
      statement on diagnostic criteria and the diagnosis and treatment of complications
      of this syndrome reached at the workshop is hereby summarized.

PMID- 14671139
TI  - Thyroid hormone and the adipocyte.

PMID- 14671140
TI  - Effects of hypo- and hyperthyroidism on noradrenergic activity and glycerol
      concentrations in human subcutaneous abdominal adipose tissue assessed with
      microdialysis.
AB  - Thyroid hormones play a major role in lipid metabolism. However, whether they
      directly affect lipolysis locally in the adipose tissue remains unknown.
      Therefore, we measured abdominal sc adipose tissue norepinephrine (NE), basal,
      and isoprenaline-stimulated lipolysis in 12 hypothyroid patients (HYPO), six
      hyperthyroid patients (HYPER), and 12 healthy controls by in vivo microdialysis.
      Adipose tissue NE was decreased in HYPO and increased in HYPER compared with
      controls (90.4 +/- 2.9 and 458.0 +/- 69.1 vs. 294.9 +/- 19.5 pmol/liter, P <
      0.01). Similarly, basal lipolysis, assessed by glycerol assay, was lower in HYPO
      and higher in HYPER than in controls (88.2 +/- 9.9 and 566.0 +/- 42.0 vs. 214.3
      +/- 5.1 micromol/liter P < 0.01). The relative magnitude of isoprenaline-induced
      glycerol increase was smaller in HYPO (39 +/- 19.4%, P < 0.05 vs. basal) and
      higher in HYPER (277 +/- 30.4%, P < 0.01) than in controls (117 +/- 5.6%, P <
      0.01). The corresponding changes in NE after isoprenaline stimulation were as
      follows: 120 +/- 9.2% (P < 0.05), 503 +/- 113% (P < 0.01), and 267 +/- 17.2 (P <
      0.01). In summary, by affecting local NE levels and adrenergic postreceptor
      signaling, thyroid hormones may influence the lipolysis rate in the abdominal sc
      adipose tissue.

PMID- 14671141
TI  - Hormones and the heart: controversies and conundrums.

PMID- 14671142
TI  - Hormone replacement therapy is associated with less coronary atherosclerosis in
      postmenopausal women.
AB  - Most observational studies indicate that hormone replacement therapy (HRT)
      protects women from cardiovascular disease. Two recent randomized trials,
      however, showed no reduction in coronary events with HRT in postmenopausal women.
      A randomized study evaluating subclinical atherosclerosis showed a beneficial
      effect of estrogen. In the current study we evaluated the association between HRT
      and coronary artery atherosclerosis, as quantified by coronary artery calcium
      score. Current users of HRT were significantly more likely to have a coronary
      artery calcium score less than 100 and were less likely to have a score greater
      than 400 than non-HRT users. After adjustment for cardiac risk factors, current
      use of HRT was associated with a significant reduction of coronary artery calcium
      score (-28; 95% confidence interval, -48 to -10). The average age of users was 59
      yr, the mean duration of use was 9 yr, and the duration of HRT use was
      significantly associated with a reduction in coronary artery calcium. These
      results suggest that HRT suppresses atherosclerosis in the coronary arteries. The
      failure to modify the cardiovascular event rate in clinical trials could result
      from the adverse effect of HRT on complicated lesions. Additional mechanistic
      studies may help identify therapeutic strategies that could maximize a potential
      benefit of HRT on early atherogenesis while minimizing adverse proinflammatory
      and procoagulant effects on complicated plaque lesions.

PMID- 14671143
TI  - Alterations in growth hormone secretory dynamics in adolescent girls with
      anorexia nervosa and effects on bone metabolism.
AB  - Anorexia nervosa (AN) is a disorder that is increasing in frequency in
      adolescents, and the age of onset is often in the prepubertal years, potentially
      affecting the development of peak bone mass and linear growth. The GH-IGF-I axis
      plays an important role in bone formation, and alterations in GH secretory
      patterns have been described in adult women with AN. However, GH secretory
      dynamics in adolescents with AN have not been described, and the effects of
      alterations in GH secretory patterns and GH concentration on bone metabolism in
      AN are not known. We examined patterns of GH secretion by deconvolutional
      analysis, and GH concentration by Cluster analysis, in adolescent girls with AN
      (n = 22) and controls (n = 20) of comparable bone age and pubertal stage. We also
      examined the roles of cortisol, leptin, and estradiol in the regulation of GH
      secretion and concentration, and the relationship of GH secretory patterns and
      concentration to bone metabolism. Basal GH secretion and secretory pulse number
      in adolescent girls with AN were increased compared with control values (P = 0.03
      and 0.007, respectively), and increased disorderliness of GH secretion
      (approximate entropy) was found in AN (P = 0.004). Mean and nadir GH
      concentrations and total area under the concentration curve were increased (P =
      0.03, 0.002, and 0.03, respectively), and IGF-I levels were decreased (P =
      0.0002) in girls with AN compared with healthy adolescent girls. IGF-I levels
      correlated negatively with nadir GH concentrations (r = -0.35; P = 0.02). Serum
      cortisol levels were higher in girls with AN than in controls (P < 0.0001) and
      correlated inversely with IGF-I (r = -0.58; P = 0.0001) and weakly with GH
      concentration (area under the concentration curve; r = -0.43; P = 0.05). A strong
      inverse relationship between markers of nutritional status (body mass index, fat
      mass, and leptin) and basal and pulsatile GH secretion, and mean and nadir GH
      concentrations was observed. GH concentration predicted levels of all markers of
      bone formation and a marker of bone resorption (N-telopeptide) in healthy
      controls, but not in AN. We demonstrate increases in basal GH secretion, number
      of secretory bursts, and GH concentration in adolescents with AN compared with
      controls, accompanied by low IGF-I levels. These data are consistent with the
      hypothesis that an acquired GH resistance occurs in this undernourished group. We
      also demonstrate that GH secretion and concentration are nutritionally regulated,
      and that the effects of nutrition exceed the effects of cortisol on GH
      concentration. Acquired GH resistance may play a role in the osteopenia and
      decreased peak bone mass frequently associated with AN.

PMID- 14671144
TI  - Enhanced granulosa cell responsiveness to follicle-stimulating hormone during
      insulin infusion in women with polycystic ovary syndrome treated with
      pioglitazone.
AB  - Women with polycystic ovary syndrome (PCOS) are known to exhibit insulin
      resistance with compensatory hyperinsulinemia. To determine the role of
      hyperinsulinemia on follicle function in PCOS, we examined 24-h estradiol (E(2))
      responses to recombinant human FSH (r-hFSH), 75 IU, before and during insulin
      infusion both before and after administration of pioglitazone (30 mg/d) in seven
      PCOS women. Each subject underwent two 10-h hyperinsulinemic-euglycemic clamps at
      rates of 30 (low dose) and 200 (high dose) mU/m(2).min, respectively. During both
      low- and high-dose insulin infusions, E(2) responses to r-hFSH were unaltered
      compared with that observed in the absence of insulin. Pioglitazone
      administration for 5 months improved insulin sensitivity as indicated by
      significantly (P < 0.05) increased glucose infusion rates during the clamp
      studies. At 3 months of treatment, r-hFSH-stimulated E(2) responses were not
      different from those observed before treatment. With pioglitazone treatment, E(2)
      responses to r-hFSH remained unchanged during low-dose insulin infusion, whereas
      a highly significant (P < 0.02) increased response was noted with the high-dose
      hyperinsulinemic-euglycemic clamp. In addition to a greater magnitude of
      response, peak levels of E(2) were sustained longer compared with that seen
      before treatment. The data indicate that granulosa cell responsiveness to FSH was
      enhanced by insulin after improved insulin sensitivity induced by pioglitazone.
      These findings are consistent with the possibility that PCOS granulosa cells are
      insulin resistant.

PMID- 14671145
TI  - Initiation of gonadotropin-releasing hormone antagonist on day 1 as compared to
      day 6 of stimulation: effect on hormonal levels and follicular development in in
      vitro fertilization cycles.
AB  - The objective of the present study was to assess the effect of altering the
      timing of GnRH antagonist initiation on the hormonal environment and follicular
      development in in vitro fertilization cycles. Sixty women undergoing in vitro
      fertilization participated in a prospective randomized controlled trial. Patients
      were stimulated with a fixed dose of 200 IU recombinant FSH, starting on d 2 of
      the cycle, and with GnRH-antagonist, starting either on d 1 (n = 30) or on d 6 of
      stimulation (n = 30). A significantly lower exposure to LH (P < 0.001) and
      estradiol (P < 0.001) during the follicular phase was observed in the d-1 group,
      compared with the d-6 group of antagonist administration. No differences in
      follicular development were seen between the two groups on either d 6 of
      stimulation or on the day of human chorionic gonadotropin administration. Similar
      fertilization rates, implantation rates, and ongoing pregnancy rates per transfer
      were, in addition, present between the two groups compared. In conclusion,
      administration of GnRH antagonist on d 1 (compared with d 6) of stimulation is
      associated with a lower exposure to LH and estradiol, which does not seem to
      affect follicular development.

PMID- 14671146
TI  - Intramyocellular lipid changes in men and women during aerobic exercise: a (1)H
      magnetic resonance spectroscopy study.
AB  - This study was designed to compare intramyocellular lipid (IMCL) changes during
      60 min of submaximal exercise in men and women. Eighteen moderately active (18-38
      yr) men (n = 9) and women (n = 9) were recruited. Maximum oxygen consumption
      (O(2)max) and body composition were used to match subjects for aerobic fitness
      and body composition. Subjects performed cycle ergometry for 1 h at 65% of
      O(2)max. Expired gases were collected throughout exercise to determine caloric
      expenditure and substrate use. Blood samples were collected before and after
      exercise to evaluate markers of lipid metabolism. Pre- and postexercise proton
      spectra were acquired from the vastus lateralis using a 3-T whole-body imaging
      system. Spectra were acquired from an 18-mm(3) region of interest (echo time = 45
      msec; repetition time = 2000 msec) for IMCL evaluation. IMCL decreased
      significantly with exercise (11.5-28.5% for men and 17.1-21.7% for women) (P <
      0.05); however, there were no significant differences between men and women.
      Although changes were found for many plasma variables [free fatty acids,
      glycerol, and norepinephrine (P < 0.05)], group differences were only evident for
      norepinephrine. In conclusion, a significant decrease in IMCL was observed during
      60 min of cycling in matched men and women.

PMID- 14671147
TI  - The calcimimetic cinacalcet normalizes serum calcium in subjects with primary
      hyperparathyroidism.
AB  - Calcimimetics increase the sensitivity of the calcium-sensing receptor (CaR) to
      circulating serum calcium, reducing the secretion of PTH and the serum calcium
      concentration. We evaluated the calcimimetic cinacalcet, a novel therapy for the
      management of primary hyperparathyroidism. In this randomized, double-blind, dose
      finding study, patients (n = 22) with primary hyperparathyroidism were given
      cinacalcet (30, 40, or 50 mg) or placebo twice daily for 15 d and observed for an
      additional 7 d. Serum calcium, plasma PTH, and 24-h and fasting urine calcium
      were measured. Baseline mean serum calcium was 10.6 mg/dl for the combined
      cinacalcet-treated patients (normal range, 8.4-10.3 mg/dl), compared with 10.4
      mg/dl for the placebo group. Mean PTH at baseline was 102 pg/ml (normal range, 10
      65 pg/ml) for the combined cinacalcet-treated patients, compared with 100 pg/ml
      in the placebo group. Serum calcium normalized after the second dose on d 1 and
      remained normal through d 15 in all cinacalcet dose groups. Maximum decreases in
      PTH of over 50% occurred 2-4 h after dosing in all cinacalcet-treated groups. The
      fasting and 24-h urine calcium to creatinine ratios were similar in the
      cinacalcet and placebo groups. This study demonstrates that cinacalcet safely
      normalized serum calcium and lowered PTH concentrations without increasing
      urinary calcium excretion in the study subjects, indicating the potential benefit
      of cinacalcet as a medical treatment for primary hyperparathyroidism.

PMID- 14671148
TI  - Pegvisomant-induced serum insulin-like growth factor-I normalization in patients
      with acromegaly returns elevated markers of bone turnover to normal.
AB  - Active acromegaly is associated with increased biochemical markers of bone
      turnover. Pegvisomant is a GH receptor antagonist that normalizes serum IGF-I in
      97% of patients with active acromegaly. We evaluated the effects of pegvisomant
      induced serum IGF-I normalization on biochemical markers of bone and soft tissue
      turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients
      (nine males; median age, 52 yr; range, 28-78 yr) with active acromegaly (serum
      IGF-I at least 30% above upper limit of an age-related reference range). Serum
      procollagen III amino-terminal propeptide (PIIINP) and type I procollagen amino
      terminal propeptide, osteocalcin (OC), bone-related alkaline phosphatase, C
      terminal cross-linked telopeptide of type I collagen (CTx), albumin-corrected
      calcium, intact PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D [1,25-(OH)(2)
      vit D], urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio, and
      urinary calcium (24 h collection) were measured (single-batch analysis) at study
      entry and after IGF-I normalization, along with sera from 32 age- and sex-matched
      controls. Compared with controls, PIIINP, OC, and CTx were significantly elevated
      in patients at baseline. Pegvisomant-induced serum IGF-I normalization (699 +/-
      76 to 242 +/- 28 micro g/liter, P < 0.001) was associated with a significant
      decrease in PIIINP, markers of bone formation (type I procollagen amino-terminal
      propeptide, OC, and bone-related alkaline phosphatase), and resorption (CTx and
      urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio). 1,25
      (OH)(2) vit D decreased and intact PTH increased significantly, but 25-hydroxy
      vitamin D was unaffected. A significant decline in calculated calcium clearance
      was observed. The decrease in serum IGF-I correlated positively with the decrease
      of serum PIIINP (r = 0.7, P < 0.01). After normalization of serum IGF-I, there
      was no statistical difference between patients and controls for any parameters
      for which control data were available. In conclusion, GH excess is associated
      with increased bone and soft tissue turnover. Pegvisomant-induced normalization
      of serum IGF-I results in a decrease in markers of bone and soft tissue turnover
      to levels observed in age-matched controls, and these changes are accompanied by
      an increase in PTH and a decrease in 1,25-(OH)(2) vit D. These data provide
      further evidence of the effectiveness of pegvisomant in normalizing the altered
      biological effects of GH hypersecretion.

PMID- 14671149
TI  - Adiponectin in human cord blood: relation to fetal birth weight and gender.
AB  - Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and
      antiatherosclerotic properties. The aim of this study was to examine whether
      adiponectin is present in human fetal blood, to define its association with fetal
      birth weight, and to evaluate whether dynamic changes in adiponectin levels occur
      during the early neonatal period. Cord blood adiponectin levels were extremely
      high (71.0 +/- 21.0 microg/ml; n = 51) compared with serum levels in children and
      adults and positively correlated with fetal birth weights (r = 0.4; P < 0.01). No
      significant differences in adiponectin levels were found between female and male
      neonates. In addition, there was no correlation between cord adiponectin levels
      and maternal body mass index, cord leptin, or insulin levels. Cord adiponectin
      levels were significantly higher compared with maternal levels at birth (61.1 +/-
      19.0 vs. 17.6 +/- 4.9 microg/ml; P < 0.001; n = 17), and no correlation was found
      between cord and maternal adiponectin levels. There were no significant
      differences between adiponectin levels at birth and 4 d postpartum (61.1 +/- 19.0
      vs. 63.8 +/- 22.0 microg/ml; n = 17). These findings indicate that adiponectin in
      cord blood is derived from fetal and not from placental or maternal tissues. The
      high adiponectin levels in newborns compared with adults may be due to lack of
      negative feedback on adiponectin production resulting from lack of adipocyte
      hypertrophy, low percentage of body fat, or a different distribution of fat
      depots in the newborns.

PMID- 14671151
TI  - Acute exposure to circularly polarized 50-Hz magnetic fields of 200-300 microT
      does not affect the pattern of melatonin secretion in young men.
AB  - Environmental exposure to time-varying (alternating current) magnetic fields
      (MFs) produced by electrical current flow is a perceived public health risk.
      Several epidemiological studies report correlations between MF exposure and
      carcinogenesis. It has been hypothesized that MF-induced suppression of melatonin
      could provide the mechanism by which this effect is mediated. Here, we describe
      results from a controlled laboratory-based study designed to detect changes in
      human melatonin secretion after a 2-h exposure to 200-300 microTesla, 50 Hz
      circularly polarized MF. Exposure was timed to occur before or during the nightly
      melatonin rise, and levels administered were some 4-6 times higher than the
      commonly encountered maximum levels. Results from 19 male subjects aged between
      18 and 35 yr indicate that acute exposure to 50 Hz MFs of this nature does not
      result in significant suppression, alteration of peak levels, or a change in
      timing of the nighttime melatonin rise. We conclude that acute exposure to 50 Hz
      MFs does not have a significant effect on the normal nighttime production of
      melatonin in young men.

PMID- 14671150
TI  - The -3826 A-->G variant of the uncoupling protein-1 gene diminishes postprandial
      thermogenesis after a high fat meal in healthy boys.
AB  - This study investigated whether the -3826 A-->G nucleotide variant of the
      uncoupling protein-1 (UCP1) gene is correlated with postprandial thermogenesis
      after a high fat meal in children. Healthy boys, aged 8-11 yr, were examined for
      resting energy expenditure and the thermic effect of a meal (TEM), which were
      measured by indirect calorimetry for 180 min after a high fat (70% fat, 20%
      carbohydrate, and 10% protein, providing 30% of the daily energy requirement) and
      a high carbohydrate meal (20% fat, 70% carbohydrate, and 10% protein). The
      sympatho-vagal activities were assessed by means of spectral analysis of the
      heart rate variability during the same period. Children were genotyped for UCP1
      polymorphism by applying a PCR-restriction fragment length polymorphism using
      buccal samples. There was no reaction of sympathetic activity to the high
      carbohydrate meal in either the GG allele or the AA+AG group and no significant
      difference in TEM. However, after the high fat meal, sympathetic responses were
      found in both groups; further, the GG allele group showed significantly lower TEM
      than the AA+AG group. In conclusion, despite fat-induced sympathetic stimulation,
      GG allele carriers have a lowered capacity of TEM in response to fat intake,
      suggesting that such impaired UCP1-linked thermogenesis can have adverse effects
      on the regulation of body weight.

PMID- 14671152
TI  - Low ghrelin concentrations in nonalcoholic fatty liver disease are related to
      insulin resistance.
AB  - Several physiological and pathophysiological conditions, including changes in
      body fat, food intake, and insulin resistance, are known to be associated with
      variations in plasma ghrelin concentrations. We tested the hypothesis that
      insulin resistance exerts a primary role by measuring ghrelin in 86 patients with
      nonalcoholic fatty liver disease (NAFLD), a condition in which insulin resistance
      is relatively independent of obesity. Compared with 40 matched healthy subjects,
      patients with NAFLD had similar glucose levels and higher plasma insulin and
      insulin resistance [homeostasis model assessment (HOMA)-R index] by over 60%.
      Ghrelin was reduced (mean +/- SD, 226 +/- 72 pmol/liter in NAFLD vs. 303 +/- 123
      in controls; P < 0.0001). In relation to quartiles of body mass index, ghrelin
      progressively decreased in controls (P = 0.003), but not in patients (P = 0.926).
      In relation to quartiles of HOMA-R, ghrelin decreased in both groups, and
      significantly correlated with HOMA-R. After adjustment for age and sex, HOMA-R
      was the sole factor significantly associated with low ghrelin in the whole group
      (odds ratio, 5.79; 95% confidence interval, 2.62-12.81; P < 0.0001) and
      specifically in NAFLD (2.96; 1.12-7.79; P = 0.028). The study suggests that
      insulin resistance is a major factor controlling ghrelin levels in subjects with
      and without NAFLD.

PMID- 14671153
TI  - CYP21 genotype, adult height, and pubertal development in 55 patients treated for
      21-hydroxylase deficiency.
AB  - In a retrospective study we evaluated long-term growth, pubertal developmental
      patterns to final height (FH), and medication in 55 patients (35 females)
      affected by 21-hydroxylase deficiency. The patients were classified into 3 groups
      according to predicted mutation severity: group A (11 women and 9 men),
      homozygous or compound heterozygous for null or In2 splice mutations [residual
      enzymatic activity (RA), <1%]; group B (11 women and 4 men), homozygous for I172N
      or R341P or R426H mutations (RA, approximately 2-3%) or compound heterozygous
      with any of the group A or B mutations; and group C (13 women and 7 men),
      homozygous for P30L or V281L or P453S mutations (RA, >30%) or compound
      heterozygous with any of the group A, B, or C mutations. Three patients showed
      unclassifiable genotypes. FH was similar in the female groups, whereas male
      patients in group B were shorter than males in groups A and C. Fifty-five percent
      of patients in group A, 33% in group B, and 40% in group C reached an FH within
      0.5 SD of target height. Four of the 7 patients diagnosed via neonatal screening
      achieved an FH equal to or above the target height. In the entire group, early
      diagnosis (<1 yr) improved height outcome. Early diagnosed CAH patients who
      received lower cortisol equivalent doses during the first year of life reached a
      better FH. Our results underline the importance of mineralocorticoid therapy, as
      CAH subjects in groups A and B who did not receive this treatment showed reduced
      FH. Early diagnosis, the use of more physiological cortisol equivalent dosages
      during the first year of life, and the extension of mineralocorticoid therapy to
      all classical patients are shown to improve the auxological outcome. Genotypic
      analysis helped to interpret the height results of our cases and prospectively
      may represent a useful tool for improving the therapeutic choice and the height
      outcome.

PMID- 14671154
TI  - Abnormal sympathoadrenal activity, but normal energy expenditure in
      hypopituitarism.
AB  - In this study of 23 hypopituitary patients and 26 healthy controls, we have
      addressed whether the obese state of substituted hypopituitary patients is
      facilitated by abnormal sympathoadrenal activity or energy expenditure (EE). All
      patients received adequate substitution therapy including GH therapy. The
      investigation program included assessment of sympathoadrenal activity (urinary
      catecholamines), body composition (dual-energy x-ray absorptiometry), appetite
      sensations (visual analog scale), and EE (indirect calorimetry in respiration
      chamber). Twenty-four-hour urinary epinephrine adjusted for lean body mass and
      fat mass was significantly lower in patients compared with controls. GH and
      hydrocortisone were single negative predictors of urinary epinephrine. The major
      determinants of EE in patients were lean body mass and fat mass, explaining 96,
      95, and 80% of the variance in 24-h EE, sleeping EE, and basal metabolic rate,
      respectively. Addition of urinary catecholamines explained another 1-4% of the
      variance in 24-h EE and basal metabolic rate, respectively. Lean patients
      exhibited significantly more hunger than obese patients and lean controls. In
      conclusion, hypopituitary patients have lower sympathoadrenal activity but normal
      EE, compared with healthy controls. This may reflect a central defect in
      hypopituitarism, however the possible impact of long-term GH and hydrocortisone
      treatment requires further attention.

PMID- 14671155
TI  - Is the thyrotropin-releasing hormone test necessary in the diagnosis of central
      hypothyroidism in children.
AB  - To determine the value of the TRH test, we analyzed the unstimulated serum T(4)
      and TSH concentrations in 54 children with central hypothyroidism. A TRH test was
      performed in 30 patients. Midline brain defects (septo-optic dysplasia, 28;
      holoprosencephaly, 2) and combined pituitary hormone deficiencies were present in
      30 and 52 patients, respectively. The mean serum free T(4), total T(4), and basal
      TSH concentrations were 0.6 ng/dl, 4.0 microg/dl, and 2.8 microU/ml,
      respectively. Five patients demonstrated elevated basal serum TSH concentrations.
      A normal TRH test [increase (delta) in TSH, 4.5-17.8], based on data from 30
      controls, was documented in 23.3% of patients. Brisk (deltaTSH, >17.8),
      absent/blunted (deltaTSH, <4.5), and delayed responses were documented in 16.7%,
      30%, and 30% of patients, respectively. The mean age at diagnosis was 2.8 yr,
      with 8 patients evolving into TSH deficiency. It was not possible to
      differentiate patients as having pituitary or hypothalamic disease based solely
      on the TRH test results. Patients with septo-optic dysplasia were diagnosed
      earlier and had elevated basal serum TSH and PRL concentrations, diabetes
      insipidus, and evolving disease. Although full pituitary function assessment is
      mandatory to identify combined pituitary hormone deficiencies, a TRH test is not
      essential, and the diagnosis should be made by serial T(4) measurements.

PMID- 14671156
TI  - Increased expression of the 25-hydroxyvitamin D(3)-1alpha-hydroxylase gene in
      alveolar macrophages of patients with lung cancer.
AB  - 25-Hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-hydroxylase) plays a central
      role in calcium metabolism by synthesizing the active hormone 1alpha,25
      dihydroxyvitamin D(3) in the kidney. Its increased expression in the extrarenal
      tissues has been found in alveolar macrophages in sarcoidosis but not in any
      other pathological conditions. We found that 1alpha-hydroxylase-mRNA in alveolar
      macrophages measured by semiquantitative RT-PCR was 2-fold greater in patients
      with lung cancer than in control subjects (0.61 +/- 0.20 vs. 0.34 +/- 0.11,
      respectively; P < 0.0001). When the clinical stages of lung cancer were divided
      into early (stage IA-IIIA) and advanced (stage IIIB and IV) and the expression of
      1alpha-hydroxylase gene was compared among the control, early, and advanced
      groups, the advanced group showed the highest expression, followed by the early
      group, then the control group (0.34 +/- 0.11, 0.52 +/- 0.11, and 0.69 +/- 0.23
      for control, early, and advanced groups, respectively; P < 0.0001). The 1alpha
      hydroxylase-mRNA level was well correlated with serum 1alpha,25-dihydroxylase
      D(3) concentration and the 1alpha,25-dihydroxylase D(3) to 25-hydroxyvitamin D(3)
      ratio, but none of the findings related to calcium metabolism among the patients
      with lung cancer. Increased local production of 1alpha,25-dihydroxyvitamin D(3)
      may be associated with the pathological conditions, such as immunosuppression, in
      lung cancer.

PMID- 14671157
TI  - Variable effects of nonsteroidal antiinflammatory agents on thyroid test results.
AB  - To investigate the effects of nonsteroidal antiinflammatory drugs (NSAIDs) on
      thyroid tests, 25 healthy subjects underwent a single-dose study and/or a 1-wk
      study. In the single-dose study, subjects received a single dose of one of six
      NSAIDs (aspirin, salsalate, meclofenamate, ibuprofen, naproxen, or indomethacin)
      at 0800 h. Total and free thyroid hormones and TSH were analyzed 0, 1, 2, 3, 4,
      and 8 h later. In the 1-wk study, subjects received one of six NSAIDs for 7 d.
      Thyroid hormones and TSH were analyzed at 0800 h each day. Total T(4) and total
      T(3) were measured by RIA, free T(4) and free T(3) were measured by equilibrium
      dialysis, and TSH was measured by immunometric assay. There were no changes in
      any hormones after a single dose or 1 wk of ibuprofen, naproxen, or indomethacin.
      Single-dose aspirin or salsalate decreased, whereas meclofenamate increased,
      various total and free thyroid hormone measurements. One week of aspirin or
      salsalate decreased total T(4), free T(4) (salsalate only), total T(3), free
      T(3), and TSH. These data confirm that aspirin, salsalate, and meclofenamate
      affect total and free thyroid hormone measurements and identify three NSAIDs that
      did not change thyroid tests. TSH remained within the normal range during acute
      or 1-wk administration of all of the NSAIDs.

PMID- 14671158
TI  - Selective reduction in cortical bone mineral density in turner syndrome
      independent of ovarian hormone deficiency.
AB  - Women with Turner syndrome (TS) are at risk for osteoporosis from ovarian failure
      and possibly from haploinsufficiency for bone-related X-chromosome genes. To
      establish whether cortical or trabecular bone is predominantly affected, and to
      control for the ovarian failure, we studied forearm bone mineral density (BMD) in
      41 women with TS ages 18-45 yr and in 35 age-matched women with karyotypically
      normal premature ovarian failure (POF). We measured BMD at the 1/3 distal radius
      (D-Rad(1/3); predominantly cortical bone) and at the ultradistal radius (UD-Rad;
      predominantly trabecular bone) by dual x-ray absorptiometry. Women with TS had
      lower cortical BMD compared with POF (D-Rad(1/3) Z-score = -1.5 +/- 0.8 for TS
      and 0.08 +/- 0.7 for POF; P < 0.0001). In contrast, the primarily trabecular UD
      Rad BMD was normal in TS and not significantly different from POF (Z-score = 
      0.62 +/- 1.1 for TS and -0.34 +/- 1.0 for POF; P = 0.26). The difference in
      cortical BMD remained after adjustment for height, age of puberty, lifetime
      estrogen exposure, and serum 25-hydroxyvitamin D (P = 0.0013). Cortical BMD was
      independent of serum IGF-I and -II, PTH, and testosterone in TS. We conclude that
      there is a selective deficiency in forearm cortical bone in TS that appears
      independent of ovarian hormone exposure and is probably related to X-chromosome
      gene(s) haploinsufficiency.

PMID- 14671159
TI  - Venous thrombosis and changes of hemostatic variables during cross-sex hormone
      treatment in transsexual people.
AB  - The incidence of venous thrombosis associated with estrogen treatment in male-to
      female (M-->F) transsexuals is considerably higher with administration of oral
      ethinyl estradiol (EE) than with transdermal (td) 17-beta-estradiol (E(2)). To
      find an explanation for the different thrombotic risks of oral EE and td E(2)
      use, we compared the effects of treatment of M-->F transsexuals with cyproterone
      acetate (CPA) only, and with CPA in combination with td E(2), oral EE, or oral
      E(2) on a number of hemostatic variables [activated protein C (APC) resistance
      and plasma levels of protein S, protein C, and prothombin], all of which are
      documented risk factors for venous thrombosis. APC resistance was determined by
      quantification of the effect of APC on the amount of thrombin generated during
      tissue factor-initiated coagulation; plasma levels of total and free protein S
      were determined by standard ELISA; and levels of prothrombin and protein C were
      determined with functional assays after complete activation of the zymogens with
      specific snake venom proteases. CPA-only, td-E(2)+CPA, or oral-E(2)+CPA treatment
      produced rather small effects on hemostatic variables, whereas oral EE treatment
      resulted in a large increase in APC resistance from 1.2 +/- 0.8 to 4.1 +/- 1 (P <
      0.001), a moderate increase in plasma protein C (9%; P = 0.012), and a large
      decrease in both total and free plasma protein S (30%; P < 0.005). The large
      differential effect of oral EE and oral E(2) indicates that the prothrombotic
      effect of EE is due to its molecular structure rather than to a first-pass liver
      effect (which they share). Moreover, these differences may explain why M-->F
      transsexuals treated with oral EE are exposed to a higher thrombotic risk than
      transsexuals treated with td E(2). Testosterone administration to female-to-male
      transsexuals had an antithrombotic effect.

PMID- 14671160
TI  - Lack of efficacy of fadrozole in treating precocious puberty in girls with the
      McCune-Albright syndrome.
AB  - We administered the aromatase inhibitor fadrozole to 16 girls with gonadotropin
      independent precocious puberty due to the McCune-Albright syndrome. The girls'
      ages ranged from 3.2-9.7 yr, and their bone ages ranged from 5.75-14.25 yr. After
      baseline evaluations, fadrozole was started at a dose of 240 microg/kg.d
      (equivalent to the dose recommended for therapy of estrogen-dependent breast
      cancer) for 12-21 months and increased to 480 microg/kg.d for an additional 12
      months in 10 girls. During treatment, seven girls had evidence of central
      precocious puberty; hence, the GnRH agonist deslorelin (4 microg/kg.d sc) was
      added to their regimen. One girl was on a long-acting GnRH agonist from the start
      of treatment. Patients were evaluated at 2-6-month intervals throughout
      treatment. After the first 6-12 months of treatment, fadrozole showed some
      benefits in 10 girls, including decrease in frequency of menses and/or rates of
      linear growth and bone maturation; however, fadrozole had no significant benefit
      in the group as a whole. The seven girls with evidence of central precocious
      puberty had no slowing in the progression of their puberty during the combined
      fadrozole and GnRH analog treatment. Adverse effects of fadrozole included
      inhibition of cortisol and aldosterone biosynthesis at the dose of 480
      microg/kg.d, without clinical evidence of adrenal insufficiency. In addition,
      three patients complained of nonspecific abdominal pain during fadrozole
      treatment. In one patient, this resolved with a reduction in dose from 480 to 240
      microg/kg.d; in two patients, it resolved spontaneously. One girl had muscle
      weakness and constipation on the 480 microg/kg.d. This resolved after
      discontinuation of the drug. We conclude that fadrozole is not sufficiently
      potent to block estrogen synthesis in most girls with gonadotropin-independent
      precocious puberty due to the McCune-Albright syndrome and may impair the
      adrenocortical stress response.

PMID- 14671161
TI  - Exercise training benefits growth hormone (GH)-deficient adults in the absence or
      presence of GH treatment.
AB  - Reduced aerobic capacity is a prominent manifestation among patients with GH
      deficiency (GHD). Exercise training may improve the physiological capacity to
      undertake aerobic activity. The ability of patients with GHD to participate in
      and benefit from a structured program of aerobic exercise with or without
      replacement recombinant human GH (rhGH) was investigated. We examined the effect
      of aerobic training on cycle ergometers in a double-blind crossover trial. Ten
      patients with GHD trained for 3 months with rhGH (6 microg/kg.d) or placebo,
      stopped both exercise and drug for 2 months, and resumed training for another 3
      months with the other agent. Peak oxygen uptake (VO(2)peak) and ventilation
      threshold (VeT) were measured during a progressive cycle ergometer test to
      fatigue or symptom-limited maximum. Serum IGF-I levels were monitored to assess
      compliance with GH treatment. VO(2)peak was low at the two baseline measures (B1,
      19.3 +/- 5.5; B2, 19.9 +/- 6.9 ml/kg.min; normal, approximately 30 ml/kg.min) as
      was VeT (B1, 11.6 +/- 2.2 ml/kg.min; B2, 11.7 +/- 2.6 ml/kg.min; normal,
      approximately 16 ml/kg.min). Exercise training increased VeT with (8.6%) or
      without (9.4%) rhGH treatment. Similarly, exercise training resulted in
      significant reduction in submaximal heart rate in the presence (-5 +/- 4 beats
      per minute; P < 0.05) or absence of rhGH treatment (-4 +/- 4 beats per minute; P
      < 0.05). Peak oxygen uptake was not significantly affected by training with or
      without rhGH treatment. Our findings suggest that exercise training is a feasible
      intervention in GH-deficient adults that can measurably improve their submaximal
      responses to exercise. The beneficial effects of exercise can mimic and are not
      additive to the effects of GH treatment alone.

PMID- 14671162
TI  - P450c17 deficiency in Brazilian patients: biochemical diagnosis through
      progesterone levels confirmed by CYP17 genotyping.
AB  - P450c17 deficiency is an autosomal recessive disorder and a rare cause of
      congenital adrenal hyperplasia characterized by hypertension, hypokalemia, and
      impaired production of sex hormones. We performed a clinical, hormonal, and
      molecular study of 11 patients from 6 Brazilian families with the combined
      17alpha-hydroxylase/17,20-lyase deficiency phenotype. All patients had elevated
      basal serum levels of progesterone (1.8-38 ng/ml; 0.57-12 pmol/liter) and
      suppressed plasma renin activity. CYP17 genotyping identified 5 missense
      mutations. The compound heterozygous mutation R362C/W406R was found in 1 family,
      whereas the homozygous mutations R96W, Y329D, and P428L were seen in the other 5
      families. The R96W mutation has been described as the cause of p450c17 deficiency
      in Caucasian patients. The other mutations were not found in 50 normal subjects
      screened by allele-specific oligonucleotide hybridization (Y329D, R362C, and
      W406R) or digestion with HphI (P428L) and were recently found in other Brazilian
      patients. Therefore, we elucidated the genotype of 11 individuals with p450c17
      deficiency and concluded that basal progesterone measurement is a useful marker
      of p450c17 deficiency and that its use should reduce the misdiagnosis of this
      deficiency in patients presenting with male pseudohermaphroditism, primary or
      secondary amenorrhea, and mineralocorticoid excess syndrome.

PMID- 14671163
TI  - Ghrelin levels correlate with insulin levels, insulin resistance, and high
      density lipoprotein cholesterol, but not with gender, menopausal status, or
      cortisol levels in humans.
AB  - The gut peptide, ghrelin, may participate in the control of energy homeostasis
      and pituitary hormone secretion in humans, stimulating both food intake and, at
      pharmacological doses, ACTH and cortisol secretion. Meal consumption and weight
      loss regulate ghrelin levels, but less is known about the relationship of ghrelin
      to body composition, aging, menopausal status, and lipid metabolism. Therefore,
      60 adult men and women of widely varying ages and weights were characterized in
      terms of body composition and levels of ghrelin, glucose, insulin, lipids, and
      cortisol. Fasting ghrelin levels correlated positively with age and negatively
      with BMI and fat cell size, but were not related to fat mass, intraabdominal fat,
      or lean mass. Fasting ghrelin levels correlated most strongly with insulin levels
      (r = -0.39; P = 0.002), insulin resistance as determined by the quantitative
      insulin sensitivity check index (r = 0.38; P = 0.003), and high-density
      lipoprotein cholesterol levels (r = 0.33; P = 0.009). Meal-induced ghrelin
      suppression correlated with the postprandial rise in insulin (r = 0.39; P <
      0.05). Ghrelin levels were similar in men and women and did not vary by
      menopausal status or in association with cortisol levels. Our data are consistent
      with the hypotheses that insulin may negatively regulate ghrelin and that high
      density lipoprotein may be a carrier particle for circulating ghrelin.

PMID- 14671164
TI  - Puberty in growth hormone-treated children born small for gestational age (SGA).
AB  - Seventy-five small for gestational age (SGA) children were studied in a
      randomized, double-blind, dose-response GH trial with either 1 or 2 mg GH/m(2).d.
      Mean (SD) age at the start of GH therapy was 7.3 (2.2) yr. Data were compared
      with Dutch reference data. In SGA boys, mean (SD) age at onset of puberty was
      12.0 (1.0) and 11.6 (0.7) yr, and in SGA girls it was 10.9 (1.1) and 10.6 (1.2)
      yr when treated with 1 and 2 mg GH/m(2).d, respectively. SGA boys treated with
      the lower GH dose started puberty later than the appropriate for gestational age
      (AGA) controls; for the other GH-dosage groups there was no significant
      difference in age at onset of puberty compared to AGA controls. The age at
      menarche and the interval between breast stage M2 and menarche were not
      significantly different for GH-treated SGA girls compared to their peers. The
      duration of puberty and pubertal height gain of GH-treated SGA boys and girls
      were not significantly different between the two GH-dosage groups and were
      comparable with untreated short children born SGA. In conclusion, long-term GH
      therapy in short SGA children has no influence on the age at onset and
      progression of puberty compared to AGA controls, regardless of treatment with a
      dose of 1 or 2 mg GH/m(2).d. Duration of puberty and pubertal height gain were
      not significantly different between the GH-dosage groups.

PMID- 14671165
TI  - An investigation of the predictors of bone mineral density and response to
      therapy with alendronate in osteoporotic men.
AB  - Male osteoporosis is an important disease, with 25-30% of all hip fractures
      occurring in men. In a recent randomized, placebo-controlled study of
      osteoporotic males, alendronate 10 mg daily for 2 yr led to significant
      increments in bone mineral density (BMD), of a similar magnitude to those
      observed in postmenopausal women. In this study, specimens collected at intervals
      during the recent trial of alendronate in male osteoporosis, from 197 of the
      original 241 participants, were assayed for testosterone, estradiol, IGF-I, IGF
      binding protein 3 (IGFBP-3), bone-specific alkaline phosphatase [BSAP (serum)],
      and N-telopeptide of type I collagen corrected for creatinine [NTx (urine)].
      Together with fracture and densitometry data from the original study,
      relationships were examined between BMD and serum IGF-I, IGFBP-3, testosterone,
      estradiol, BSAP, and urine NTx, both at baseline and during treatment with
      alendronate, to gain possible insights into the pathogenesis of male
      osteoporosis. Statistically significant (P <or= 0.05) associations were
      documented, at baseline, between the presence of vertebral fracture and each of
      serum IGF-I, serum IGFBP-3, serum free testosterone, total spine BMD, and total
      body BMD. No statistically significant correlations were observed between any of
      the baseline variables (IGF-I, IGFBP-3, estradiol, testosterone, and presence of
      vertebral fracture) and the BMD response to alendronate at any site. In a
      multivariate analysis, used to identify possible combinations of factors capable
      of predicting baseline BMD or response to alendronate, statistically significant
      (P <or= 0.01) relationships were seen, at baseline, between BMD and body mass
      index, age, and prior fracture. However, no statistically significant
      relationships were seen between any of the baseline variables (age, body mass
      index, testosterone, estradiol, IGF-I, IGFBP-3, and prior fracture) and change in
      BMD at any site. These data suggest that among men with osteoporosis it is not
      possible to identify patients who would be particularly good candidates for
      therapy with alendronate on the basis of biochemical or hormonal markers.
      Alendronate therapy appears to benefit osteoporotic males equally, irrespective
      of baseline serum testosterone, estradiol, IGF-I, or markers of bone turnover.

PMID- 14671166
TI  - Low vitamin D and high parathyroid hormone levels as determinants of loss of
      muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study
      Amsterdam.
AB  - The age-related change in hormone concentrations has been hypothesized to play a
      role in the loss of muscle mass and muscle strength with aging, also called
      sarcopenia. The aim of this prospective study was to investigate whether low
      serum 25-hydroxyvitamin D (25-OHD) and high serum PTH concentration were
      associated with sarcopenia. In men and women aged 65 yr and older, participants
      of the Longitudinal Aging Study Amsterdam, grip strength (n = 1008) and
      appendicular skeletal muscle mass (n = 331, using dual-energy x-ray
      absorptiometry) were measured in 1995-1996 and after a 3-yr follow-up. Sarcopenia
      was defined as the lowest sex-specific 15th percentile of the cohort, translating
      into a loss of grip strength greater than 40% or a loss of muscle mass greater
      than 3%. After adjustment for physical activity level, season of data collection,
      serum creatinine concentration, chronic disease, smoking, and body mass index,
      persons with low (<25 nmol/liter) baseline 25-OHD levels were 2.57 (95%
      confidence interval 1.40-4.70, based on grip strength) and 2.14 (0.73-6.33, based
      on muscle mass) times more likely to experience sarcopenia, compared with those
      with high (>50 nmol/liter) levels. High PTH levels (>or=4.0 pmol/liter) were
      associated with an increased risk of sarcopenia, compared with low PTH (<3.0
      pmol/liter): odds ratio = 1.71 (1.07-2.73) based on grip strength, odds ratio =
      2.35 (1.05-5.28) based on muscle mass. The associations were similar in men and
      women. The results of this prospective, population-based study show that lower 25
      OHD and higher PTH levels increase the risk of sarcopenia in older men and women.

PMID- 14671167
TI  - Treatment of recurrent thyroid cysts with ethanol: a randomized double-blind
      controlled trial.
AB  - Thyroid nodules are prevalent; when evaluated by ultrasonography (US), 15-25% of
      solitary thyroid nodules are cystic or predominantly cystic, and most are benign.
      Simple aspiration is the treatment of choice, but the recurrence rate is 10-80%
      depending on the number of aspirations and the cyst volume. The aim of this study
      was to evaluate the effect on recurrence rate of benign recurrent thyroid cysts
      in a double-blind randomized study comparing ethanol instillation with
      instillation of isotonic saline and subsequent complete emptying. Sixty-six
      consecutive patients with recurrent and benign (based on US-guided biopsy)
      thyroid cysts (>or=2 ml) were randomly assigned to either subtotal cyst
      aspiration, flushing with 99% ethanol, and subsequent complete fluid aspiration
      (n = 33), or to subtotal cyst aspiration, flushing with isotonic saline, and
      subsequent complete fluid aspiration (n = 33). In case of recurrence (defined as
      cyst volume >1 ml) at the monthly evaluations, the treatment was repeated but
      limited to a maximum of three treatments. Procedures were US-guided, and patients
      were followed for 6 months. Age, sex, number of previous aspirations,
      pretreatment cyst volume, and serum TSH did not differ in the two groups. Cure
      (defined as a cyst volume <or=1 ml at the end of follow-up) was obtained in 27 of
      33 [82%; confidence interval (CI), 65-93] patients treated with ethanol and in 16
      of 33 (48%; CI, 31-66) patients treated with saline (P = 0.006). In the ethanol
      group, 21 of 33 (64%) patients were cured after one session only, compared with
      six of 33 (18%) in the saline group (P = 0.002). The number of previous
      aspirations (P = 0.005) and baseline cyst volume (P = 0.005) had influence on
      outcome, i.e. the chance of success decreased with the number of previous
      aspirations and with increasing cyst volume. Seven patients (21%) treated with
      ethanol had moderate to severe pain (median duration, 5 min; CI, 2-10), and one
      had transient dysphonia. Indirect laryngoscopy was performed before and after the
      last session and was normal in all patients. We concluded that treatment of
      recurrent thyroid cysts with ethanol is superior to simple aspiration and
      flushing with saline and devoid of serious side effects. Our study demonstrates
      that flushing with ethanol is a clinically significant nonsurgical alternative
      for thyroid cysts that recur despite repeat aspirations.

PMID- 14671168
TI  - Patients with Van Buchem disease, an osteosclerotic genetic disease, have
      elevated bone formation markers, higher bone density, and greater derived polar
      moment of inertia than normal.
AB  - Van Buchem disease is an autosomal recessive disease characterized by overgrowth
      of the skeleton. In a group of Dutch patients the disease is thought to be due to
      a 52-kb deletion that results in decreased expression of the SOST gene. To
      further characterize the disease, the morphology of the metacarpals of six adult
      subjects and two juveniles with Van Buchem disease were measured on hand x-rays
      along with nine normal adults and nine adult carriers of the disease. Serum bone
      formation markers, alkaline phosphatase, type I procollagen peptide, and
      osteocalcin, and the urinary bone resorption marker, cross-linked N-telopeptide,
      were determined. Van Buchem patients had increased metacarpal outer diameter,
      inner diameter, cortical thickness, and bone mineral density. Calculated bone
      volume and derived polar moment of inertia were markedly elevated (elevations of
      158 +/- 33% and 497 +/- 95%, respectively) consistent with increased bone
      strength. Serum procollagen peptide and osteocalcin were significantly higher in
      Van Buchem patients. Urinary cross-linked N-telopeptide was significantly
      elevated in Van Buchem patients. None of these changes was found in Van Buchem
      carriers. These observations indicate that decreased expression of the SOST gene
      can lead to increased bone formation and to stronger bones.

PMID- 14671169
TI  - High risk of adrenal insufficiency in adults previously treated for idiopathic
      childhood onset growth hormone deficiency.
AB  - The aim was to reevaluate a group of adults treated for idiopathic childhood
      onset GH deficiency (GHD) after 18 yr without GH treatment. Twenty-six (11
      females) patients participated. All but two had isolated GHD. Childhood diagnosis
      was established by insulin tolerance test (ITT). The patients were retested with
      an ITT to evaluate adult GH status. In five patients, an arginine and a synacthen
      test were performed instead of an ITT. Eleven of 25 patients had a subnormal
      cortisol response to ITT or synacthen. Ten patients had a GH peak less than 3.0
      microg/liter (0.5. +/- 0.5 microg/liter), whereas 16 patients displayed a normal
      GH response (12.3 +/- 10.6 microg/liter) after ITT. IGF-I values were decreased
      in the patients with a pathological retest as well as in patients with a normal
      GH response compared with controls (P < 0.005). In 26 idiopathic childhood onset
      GHD patients, 44% of the patients had developed adrenal insufficiency; 38.5% had
      persistent GHD in adulthood, using the same test in both childhood and adulthood.
      Patients having a normal GH test had decreased IGF-I levels, compared with
      controls, indicating impaired function of a seemingly normal GH axis. It is
      imperative that pituitary axes other than the GH axis are tested at regular
      intervals, even in the absence of GHD in adulthood.

PMID- 14671170
TI  - Screening for congenital adrenal hyperplasia: adjustment of 17
      hydroxyprogesterone cut-off values to both age and birth weight markedly improves
      the predictive value.
AB  - Newborn screening procedures for congenital adrenal hyperplasia (CAH) are still
      suboptimal because of low specificity, particularly in premature infants. This
      study evaluated a multitiered strategy for reporting abnormal 17
      hydroxyprogesterone screening values that simultaneously takes into account not
      only birth weight but also age at sampling. A cautious three-tiered cut-off
      scheme was used during the initial 24 months of CAH screening in Bavaria. Data
      were then reanalyzed using five birth weight classes to reflect more precisely
      the markedly higher values in low-birth-weight newborns. Because 17
      hydroxyprogesterone values apparently decline with increasing age, these classes
      were then further subdivided into a total of 21 groups according to the age at
      sampling. Based on this reanalysis, we defined new multitiered cut-off levels and
      used them for the next 18 months. A total of 538466 newborns were screened from
      January 1999 to June 2002; 51 CAH cases were detected. Application of the new
      threshold values resulted in a 35% reduction of the total recall rate (from 1.13%
      to 0.74%) and an increase in the positive predictive value from 0.84% to 1.29%
      without reducing diagnostic sensitivity. This improvement of CAH screening can be
      achieved by simply using request forms that ask for both age and birth weight at
      the time of sampling.

PMID- 14671171
TI  - Leptin and bone mineral density: a cross-sectional study in obese and nonobese
      men.
AB  - Leptin has been suggested to decrease bone mineral density (BMD). This
      observational analysis explored the relationship between serum leptin and BMD in
      327 nonobese men (controls) (body mass index 26.1 +/- 3.7 kg/m(2), age 49.9 +/-
      6.0 yr) and 285 juvenile obese men (body mass index 35.9 +/- 5.9 kg/m(2), age
      47.5 +/- 5.1 yr). Whole-body dual-energy x-ray absorptiometry scan measured BMD,
      fat mass, and lean mass. Fasting serum leptin (nanograms per milliliter) was
      strongly associated with fat mass (kilograms) in both controls (r = 0.876; P <
      0.01) and juvenile obese (r = 0.838; P < 0.001). An inverse relation between BMD
      adjusted for body weight and serum leptin emerged in both the control group (r = 
      0.186; P < 0.01) and the juvenile obese group (r = -0.135; P < 0.05). In a
      multiple linear regression, fat mass, lean body mass, and occupational physical
      activity were positively associated with BMD in the control group, whereas in the
      juvenile obese, only lean body mass was positively associated with BMD and
      smoking negatively associated with BMD. Our study supports that leptin is
      inversely associated with BMD and may play a direct role in the bone metabolism
      in nonobese and obese Danish males, but it also stresses the fact that the strong
      covariation between the examined variables is a shortcoming of the cross
      sectional design.

PMID- 14671172
TI  - Quality of life, psychosocial well-being, and sexual satisfaction in women with
      polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by
      chronic anovulation and hyperandrogenism. PCOS is one of the leading causes of
      infertility and manifests with hirsutism, acne, and obesity. To investigate its
      impact on health-related quality of life and sexuality, 50 women with PCOS and 50
      controls were evaluated with standardized questionnaires (36-item short-form
      health survey, symptom checklist revised, and life satisfaction questionnaire).
      The impact of hirsutism, obesity, and infertility was assessed using five-point
      rating scales, and sexual satisfaction was analyzed with visual analog scales.
      Patients showed greater psychological disturbances on the symptom checklist
      revised dimensions, obsessive-compulsive, interpersonal sensitivity, depression,
      anxiety, aggression, and psychoticism, along with a lower degree of life
      satisfaction in the life satisfaction questionnaire scales health, self, and sex.
      Health-related quality of life measured with the 36-item short-form health survey
      revealed significantly decreased scores for physical role function, bodily pain,
      vitality, social function, emotional role function, and mental health in patients
      with PCOS. Although patients had the same partner status and frequency of sexual
      intercourse, they were significantly less satisfied with their sex life and found
      themselves less attractive. Most of the differences were not affected by
      correction for body weight. In conclusion, PCOS causes a major reduction in the
      quality of life and severely limits sexual satisfaction.

PMID- 14671173
TI  - Occult Cushing's syndrome in type-2 diabetes.
AB  - Subclinical Cushing's syndrome (SCS) caused by adrenal incidentalomas is
      frequently associated with overweight and insulin resistance. Metabolic syndrome
      X may therefore be a clue to the presence of CS. However, the incidence of CS in
      this situation remains unknown. We have conducted a prospective study to evaluate
      the prevalence of occult CS in overweight, type-2 diabetic patients devoided of
      specific clinical symptoms of CS. Two hundred overweight, type-2 diabetic
      patients, consecutively referred for poor metabolic control (HbA(1C) > 8%), were
      studied as inpatients. A first screening step was performed with the 1-mg
      overnight dexamethasone suppression test (DST) using a revised criterion for
      cortisol suppression (60 nmol/liter) to maximize the sensitivity of the
      procedure. A second confirmatory step of biochemical investigations (midnight
      plasma cortisol concentration, plasma cortisol circadian rhythm, morning plasma
      ACTH concentration, 24-h urinary free cortisol, and 4-mg i.v. DST) was performed
      in patients with impaired 1-mg DST. A third step of imaging studies was performed
      according to the results of second-step investigations. Fifty-two patients had
      impaired 1-mg DST. Among these, 47 were further evaluated. Thirty were considered
      as false positives of the 1-mg DST, whereas 17 displayed at least one additional
      biological abnormality of the hypothalamic-pituitary-adrenal axis. Definitive
      occult CS was identified in four patients (2% of the whole series) with Cushing's
      disease (n = 3) and surgically proven adrenal adenoma (n = 1). Definitive
      diagnosis remains to be established in seven additional patients (3.5%) with mild
      occult CS associated with unsuppressed plasma ACTH concentrations and a
      unilateral adrenal tumor of 10-29 mm in size showing prevalent uptake at
      radiocholesterol scintigraphy. In conclusion, a relatively high prevalence of
      occult CS was found in our study. Further studies are needed to evaluate the
      impact of the cure of occult CS on obesity and diabetes mellitus in these
      patients. Such studies might provide a rationale for systematic screening of
      occult CS in this population.

PMID- 14671174
TI  - Computed tomography-guided percutaneous acetic acid injection therapy for
      functioning adrenocortical adenoma.
AB  - We reported the outcomes of computed tomography (CT)-guided percutaneous acetic
      acid injection therapy for functioning adrenocortical adenomas. With the patient
      in a prone position, the puncture needle was inserted vertically downward into
      the adenoma with frequent CT scanning. After confirmation by pilot injection with
      contrast medium, a small aliquot of 40-50% acetic acid was injected and repeated.
      Between 1997 and 2002, 18 sessions of CT-guided injection therapy, including one
      session of ethanol injection, were performed on 10 patients (five patients with
      primary aldosteronism and five patients with Cushing's or subclinical Cushing's
      syndrome) without any complications except transient upper abdominal pain during
      the acetic acid injection. The follow-up period ranged from 5-69 months. The
      treatment resulted in almost an extirpation of the adrenocortical hyperfunction
      in seven patients after one or two sessions. CT-guided percutaneous acetic acid
      injection might be a simple, cost-effective, and far less invasive treatment for
      small functioning adrenocortical adenomas.

PMID- 14671175
TI  - Testosterone undecanoate maintains spermatogenic suppression induced by
      cyproterone acetate plus testosterone undecanoate in normal men.
AB  - In this study we evaluated whether testosterone undecanoate (TU), alone or
      combined with low dose cyproterone acetate (CPA), can maintain spermatogenic
      suppression induced by higher doses of CPA plus TU. Twenty-four men received for
      12 wk 20 mg/d CPA plus 1000 mg/6 wk TU and then 1000 mg/8 wk TU plus 20 mg/d CPA
      (n = 8), 2 mg/d CPA (n = 8), or plus placebo (n = 8) for 32 wk. Blood samples,
      physical examinations, hormones, chemistry, hematology, semen analysis, and
      sexual/behavioral assessments were performed throughout the study. Sperm counts
      decreased to less than 1 million/ml in all subjects by wk 12, and 54% of them
      achieved azoospermia. Suppression of sperm counts was maintained until wk 44.
      Serum LH and FSH levels were suppressed by wk 12 of hormone administration and
      remained suppressed until wk 44. No significant changes in any biochemical
      parameters were detected at wk 44 in any group. There was a slight increase in
      total prostate volume to within the normal range at wk 44 that returned to
      baseline 1 yr after stopping hormone administration. In conclusion, TU alone or
      combined with lower doses of CPA maintains sperm suppression induced by higher
      dose CPA plus TU for 32 wk. This prototype regimen represents a promising male
      contraceptive regimen.

PMID- 14671176
TI  - Short- and long-term effects of growth hormone (GH) replacement on protein
      metabolism in GH-deficient adults.
AB  - Reduced fat-free mass (FFM) in GH-deficient (GHD) adults is improved by GH
      replacement, but the protein metabolic changes are unclear. Using iv
      [(2)H(3)]leucine and oral l-[(13)C(1)]leucine infusions and dual emission x-ray
      absorptiometry, we compared leucine kinetics and body composition in eight GHD
      adults and eight healthy controls in the fasted and fed states, before and after
      2 wk and 6 months of GH replacement. Leucine kinetics were not different between
      pretreatment GHD subjects and controls. After 2 wk of GH treatment, leucine
      oxidation decreased in the GHD subjects compared with baseline values [fasted, 41
      +/- 6 vs. 30 +/- 5 micromol/kg FFM.h (P < 0.01); fed, 49 +/- 3 vs. 41 +/- 3.6
      micromol/kg FFM.h (P < 0.05)], leucine balance improved [fasted, -14 +/- 4 vs. 
      3.5 +/- 3 micromol/kg FFM.h (P < 0.01); fed, 65 +/- 10 vs. 72 +/- 7 micromol/kg
      FFM.h (P = 0.07)], and protein synthesis increased [fasted, 116 +/- 5 vs. 131 +/-
      6 micromol/kg FFM.h (P < 0.05); fed, 103 +/- 6 vs. 116 +/- 6 micromol/kg FFM.h (P
      < 0.05)]. After 6 months of GH treatment, these changes were not maintained in
      the fed state. The five GHD subjects with decreased FFM at baseline showed a
      significant increase after 6 months of GH treatment (P < 0.05). GH replacement in
      GHD acutely improves protein balance by stimulating synthesis and inhibiting
      catabolism. After 6 months, protein kinetics reached a new homeostasis to
      maintain the net gain in FFM.

PMID- 14671177
TI  - Cyclical Cushing's syndrome in a patient with a bronchial neuroendocrine tumor
      (typical carcinoid) expressing ghrelin and growth hormone secretagogue receptors.
AB  - A 56-yr-old woman was referred with a diagnosis of Cushing's disease.
      Hypertension and severe hypokalemia were present and high urinary free
      cortisol/cortisone ratio was detected, raising a suspicion of an ectopic ACTH
      syndrome. Inferior petrosal sinus sampling, thoracic computed tomography, and
      octreotide scans were negative. Remission and relapse periods lasting 3-4 months
      were observed during the 3.5 yr of follow-up. Finally a thoracic computed
      tomography scan showed a basal paracardic nodule in the left lung. After surgery,
      a well-differentiated neuroendocrine tumor (typical bronchial carcinoid) was
      diagnosed, staining positively for ACTH. RT-PCR revealed expression of
      proopiomelanocortin, CRH receptor, and V3 vasopressin receptor. Somatostatin
      receptor type 1, 2, 3, and 5 mRNA was detected only in tumoral tissue.
      Interestingly, we observed the simultaneous presence of ghrelin and both GH
      secretagogue (GHS) receptors (1a and 1b) mRNA in tumoral tissue but not in the
      normal lung. This finding correlates with the in vivo ACTH hyperresponsiveness to
      hexarelin (a GHS). This is the first report of a cyclical ectopic ACTH-secreting
      tumor with an in vivo ACTH response to hexarelin coupled with the tumoral
      expression of ghrelin and GHS receptors. This finding might imply an
      autocrine/paracrine modulatory effect of ghrelin in bronchial ACTH-secreting
      tumors.

PMID- 14671178
TI  - Deletion of codons 88-92 of the melanocortin-4 receptor gene: a novel deleterious
      mutation in an obese female.
AB  - Genetic and pharmacological studies have shown that the melanocortin-4 receptor
      (MC4R) is an important regulator of food intake and energy homeostasis.
      Consistent with these studies, several mutations of the MC4R gene have been
      identified as being associated with early-onset severe obesity. We report here
      the first in-frame deletion mutation of the MC4R gene (delta88-92) in an obese
      female patient with onset of obesity at less than 5 yr of age. Functional
      analysis revealed that the mutant receptor is expressed well on the cell surface
      but completely devoid of ligand binding and cAMP generation in response to
      agonist stimulation. We conclude that this novel mutation is the cause of obesity
      of this patient.

PMID- 14671179
TI  - The effect of mifepristone on the expression of steroid hormone receptors in
      human decidua and placenta: a randomized placebo-controlled double-blind study.
AB  - The objective of this study was to investigate the expression of steroid hormone
      receptors in human first trimester placenta and decidua and whether such
      expression was altered after mifepristone treatment. One hundred women who
      requested termination of pregnancy between 7 and 12 wk were randomly assigned to
      receive placebo or 200 mg mifepristone at 12, 24, and 48 h before suction
      evacuation of uterus. Immunohistochemistry was used to detect the expression of
      progesterone receptor, estrogen receptor, glucocorticoid receptor (GR), and
      androgen receptor. Progesterone receptor expression in both placenta and decidua
      tissues was not affected by mifepristone treatment. Estrogen receptor was
      identified in a decidual gland in only one sample. Androgen receptor was not
      expressed in either tissue. The expression of GR in decidual stromal cells was
      suppressed by mifepristone, and the effect was detectable at 12 h after
      administration. The expression of GR in decidual glands was not affected. In the
      placenta, the expression of GR in cytotrophoblasts and villous stromal cells was
      suppressed by mifepristone; the effect was detectable at 12 h and persisted at 48
      h. In conclusion, the suppressed GR expression after mifepristone administration
      may be part of the mechanism of mifepristone in causing abortion.

PMID- 14671180
TI  - Central congenital hypothyroidism due to gestational hyperthyroidism: detection
      where prevention failed.
AB  - Much worldwide attention is given to the adverse effects of maternal Graves'
      disease on the fetal and neonatal thyroid and its function. However, reports
      concerning the adverse effects of maternal Graves' disease on the pituitary
      function, illustrated by the development of central congenital hypothyroidism
      (CCH) in the offspring of these mothers, are scarce. We studied thyroid hormone
      determinants of 18 children with CCH born to mothers with Graves' disease. Nine
      mothers were diagnosed after pregnancy, the majority after their children were
      detected with CCH by neonatal screening. Four mothers were diagnosed during
      pregnancy and treated with antithyroid drugs since diagnosis. Another four
      mothers were diagnosed before pregnancy, but they used antithyroid drugs
      irregularly; free T(4) concentrations less than 1.7 ng/dl (<22 pmol/liter) were
      not encountered during pregnancy. All neonates had decreased plasma free T(4)
      concentrations (range 0.3-0.9 ng/dl, 3.9-11.5 pmol/liter); plasma TSH ranged
      between 0.1 and 6.6 mU/liter. TRH tests showed pituitary dysfunction. Seventeen
      children needed T(4) supplementation. Because all mothers were insufficiently
      treated during pregnancy, it is hypothesized that a hyperthyroid fetal
      environment impaired maturation of the fetal hypothalamic-pituitary-thyroid
      system. The frequent occurrence of this type of CCH (estimated incidence 1:35000)
      warrants early detection and treatment to minimize the risk of cerebral damage. A
      T(4)-based screening program appears useful in detecting this type of CCH.
      However, the preferential and presumably best strategy to prevent CCH caused by
      maternal Graves' disease is preserving euthyroidism throughout pregnancy.

PMID- 14671181
TI  - Long-term predictive value of postsurgical cortisol concentrations for cure and
      risk of recurrence in Cushing's disease.
AB  - We assessed the value of postoperative plasma cortisol concentrations to predict
      cure and recurrence of Cushing's disease after transsphenoidal surgery (TS).
      Seventy-eight of 80 consecutive patients treated by TS for Cushing's disease were
      evaluated. TS cured 72% (n = 56) of the patients. Two weeks after surgery,
      patients with plasma cortisol levels below 138 nmol/liter (n = 50; three
      macroadenomas) and eight (27%) of 30 patients (nine macroadenomas) with cortisol
      greater than 138 nmol/liter were cured. Six (five with a macroadenoma) of these
      eight patients had cortisol values less than 50 nmol/liter 3 months after
      surgery. Therefore, the optimal cut-off value of cortisol predicting remission
      was 138 nmol/liter, measured 3 months after surgery (positive and negative
      predictive values 87 and 90%, respectively). Five patients (9%) had recurrent
      Cushing's disease during a median follow-up of 7 yr. Recurrence occurred in four
      of 24 (17%) patients with a follow-up of more than 10 yr. Therefore, cortisol
      levels above 138 nmol/liter, obtained 2 wk after TS, should be repeated, because
      they do not predict persistent Cushing's disease in 27% of those patients.
      Postoperative cortisol levels do not positively predict recurrence of disease
      during long-term follow-up of initially cured patients.

PMID- 14671182
TI  - Seeking the optimal target range for insulin-like growth factor I during the
      treatment of adult growth hormone disorders.
AB  - Impaired GH activity at target tissues, occurring when GH action is blocked or
      during suboptimal GH replacement therapy, may result in a pathological state
      associated with lowering of IGF-I, but not GH levels. Such a state represents
      functional but not necessarily actual GH deficiency (GHD). The aim of this study
      was to identify a range of IGF-I values commensurate with GHD, which could be
      used to determine the risk of functional GHD during the treatment of adult GH
      disorders. Centrally measured baseline IGF-I data from the Kabi International
      Metabolic Study European GHD database were analyzed. Inclusion criteria were
      adult-onset GHD and two or more additional anterior pituitary hormone deficits.
      Adults with childhood-onset GHD and cured acromegaly were excluded. The cohort
      was stratified into six gender-based age ranges. Baseline IGF-I measurements from
      376 females (median age, 48 yr; range, 21-77 yr) and 434 males (median age 52 yr;
      range 21-80 yr) were analyzed. Data were not normally distributed and are
      presented as medians (quartiles). The median serum IGF-I and IGF-I SDS in males
      were 94.0 microg/liter (64 and 141) and -1.52 (-2.53 and -0.456; n = 434). Both
      were significantly greater than the equivalent values of females, which were 73
      microg/liter (46 and 103.5) and -2.30 (-3.28 and -1.328; n = 376; P < 0.0001 for
      both). Age and gender-related 90th and 95th percentiles for IGF-I SDS were
      determined to generate risk estimates for functional GHD, which, in conjunction
      with the clinical status of the patient, may be used to aid dose titration during
      treatment of GH disorders in adulthood.

PMID- 14671183
TI  - No increase of blocking type anti-thyrotropin receptor antibodies during
      pregnancy in patients with Graves' disease.
AB  - Serial changes in serum levels of anti-TSH receptor antibodies were examined
      during and after pregnancy in six patients with Graves' disease receiving no or
      minimal maintenance doses of antithyroid drugs. During pregnancy, serum levels of
      TSH-binding inhibitory Igs (P < 0.001) and thyroid-stimulating antibodies (TSAbs)
      (P < 0.01) decreased gradually but increased after delivery in all patients.
      Activities of thyroid-stimulation blocking antibodies (TSBAbs) were lower than
      the cut-off value in early pregnancy, and values significantly decreased in four
      patients during pregnancy. The other two patients showed no significant change
      during pregnancy. In contrast, TSBAb levels increased significantly (P < 0.01)
      after delivery in all patients. We found that activities of TSH-binding
      inhibitory Igs, TSAb, and TSBAb decrease during pregnancy and increase after
      delivery, suggesting that amelioration of Graves' disease during pregnancy is
      induced by decrease of TSAb but not by the appearance of TSBAb.

PMID- 14671184
TI  - Evaluation of insulin sensitivity in healthy volunteers treated with olanzapine,
      risperidone, or placebo: a prospective, randomized study using the two-step
      hyperinsulinemic, euglycemic clamp.
AB  - The primary objective of this study was to evaluate insulin sensitivity in
      healthy subjects treated with olanzapine or risperidone. Subjects were randomly
      assigned to single-blind therapy with olanzapine (10 mg/d), risperidone (4 mg/d),
      or placebo for approximately 3 wk. Insulin sensitivity was assessed pre- and
      posttreatment using a 2-step, hyperinsulinemic, euglycemic clamp. Glucose and
      insulin responses were also assessed by a mixed meal tolerance test. Of the 64
      subjects randomized, 22, 14, and 19 in the olanzapine, risperidone, and placebo
      groups, respectively, completed the study procedures. There were no significant
      within-group changes in the glucose disposal rate or the insulin sensitivity
      index for the active therapy groups. Further, the results of the mixed meal
      tolerance test did not demonstrate clinically significant changes in integrated
      glucose metabolism during treatment with these medications. In summary, this
      study did not demonstrate significant changes in insulin sensitivity in healthy
      subjects after 3 wk of treatment with olanzapine or risperidone.

PMID- 14671185
TI  - Adiponectin gene expression in subcutaneous adipose tissue of obese women in
      response to short-term very low calorie diet and refeeding.
AB  - Adiponectin is an adipocyte-derived protein suggested to be involved in energy
      homeostasis and in lipid and glucose metabolism. Little is known regarding the
      consequence of acute changes in energy balance on adiponectin mRNA expression in
      human adipose tissue. Using a real-time RT-PCR assay, we investigated the effects
      of 2-d very low calorie diet (VLCD) and subsequent refeeding on adiponectin mRNA
      expression in sc adipose tissue of morbidly obese women. Basal adiponectin mRNA
      abundance of the obese women showed a wide distribution (2.6-14.3 mRNA/18S rRNA;
      coefficient of variation, 51.2%) and was significantly lower than that of lean
      controls (P < 0.001). In the obese group, the VLCD caused a 33% rise (P < 0.01)
      in the average level of mRNA, whereas refeeding caused a 32.8% fall (P < 0.05).
      In contrast, the change in leptin mRNA expression with either VLCD or refeeding
      was not statistically significant. The obese subjects who showed an acute
      adiponectin mRNA response to the changes in energy intake had a higher basal
      level of adiponectin mRNA (P = 0.02) and a borderline-significantly lower body
      mass index compared with the subjects who showed no or weak adiponectin mRNA
      response. Insulin sensitivity of the responder subgroup significantly increased
      by 89% (P = 0.008) after the VLCD, whereas insulin sensitivity of the
      nonresponder subgroup only increased by 24% (P = 1.56). This study indicates that
      adiponectin mRNA in sc adipose tissue can acutely respond to short-term energy
      changes in some obese subjects. Both the levels of adiposity and insulin
      sensitivity may contribute to the variation in adiponectin gene expression in
      response to acute energy changes.

PMID- 14671186
TI  - Exon 6 and 2 peroxisome proliferator-activated receptor-gamma polymorphisms in
      polycystic ovary syndrome.
AB  - Obesity affects about 44% of women with polycystic ovary syndrome (PCOS).
      Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is one of the genes
      involved in the differentiation of adipose tissue. In an attempt to shed light on
      the high percentage of obesity in PCOS, we examined polymorphisms at exons 6 and
      2 of the PPAR-gamma gene in 100 PCOS patients and in 100 healthy controls matched
      for age and body mass index (BMI). The T allele frequency of exon 6 was
      significantly higher (P < 0.05) in PCOS patients compared with control women. In
      addition, the BMI and leptin levels were significantly higher (P < 0.05) in PCOS
      patients carrying the C-->T substitution than in controls. There was no
      significant difference in leptin levels after normalization for BMI. The
      Pro(12)Ala polymorphism at exon 2 was unrelated to BMI and/or leptin levels in
      PCOS women. In conclusion, the higher frequency of the C-->T substitution in exon
      6 of the PPAR-gamma gene in PCOS women suggests that it plays a role in the
      complex pathogenetic mechanism of obesity in PCOS, whereas the Pro(12)Ala
      polymorphism does not seem to affect BMI in PCOS women.

PMID- 14671187
TI  - A novel semiquantitative polymerase chain reaction/enzyme digestion-based method
      for detection of large scale deletions/conversions of the CYP21 gene and mutation
      screening in Turkish families with 21-hydroxylase deficiency.
AB  - 21-Hydroxylase deficiency is a recessively inherited disorder resulting from
      mutations in the CYP21 gene. The CYP21 gene is located along with the CYP21P
      pseudogene in the human leukocyte antigen major histocompatibility complex region
      on chromosome 6. Molecular diagnosis is difficult due to the 98% similarity of
      CYP21 and CYP21P genes and the fact that almost all frequently reported mutations
      reside on the pseudogene. Allele-specific PCR for the 8 most frequently reported
      point mutations was performed in 31 Turkish families with at least a single 21
      hydroxylase-deficient individual. The allele frequencies of the point mutations
      were as follows: P30L, 0%; IVS2 (AS,A/C-G,-13), 22.5%; G110delta8nt, 3.2%; I172N,
      11.4%; exon 6 cluster (I236N, V237E, M239K), 3.2%; V281L, 0%; Q318X, 8%; and
      R356W, 9.6%. Large deletions and gene conversions were detected by Southern blot
      analysis, and the allele frequencies were 9.6% and 22.5%, respectively. Sequence
      analysis of the gene, performed on patients with only 1 mutated allele, revealed
      2 missense mutations (R339H and P435S). A novel semiquantitative PCR/enzyme
      digestion-based method for the detection of large scale deletions/conversions of
      the gene was developed for routine diagnostic purposes, and its accuracy was
      shown by comparison with the results of Southern blot analysis.

PMID- 14671188
TI  - Molecular changes underlying reduced pineal melatonin levels in Alzheimer
      disease: alterations in preclinical and clinical stages.
AB  - A disturbed sleep-wake rhythm is common in Alzheimer disease (AD) patients and
      correlated with decreased melatonin levels and a disrupted circadian melatonin
      rhythm. Melatonin levels in the cerebrospinal fluid are decreased during the
      progression of AD neuropathology (as determined by the Braak stages), already in
      cognitively intact subjects with the earliest AD neuropathology (Braak stages I
      II) (preclinical AD). To investigate the molecular mechanisms behind the
      decreased melatonin levels, we measured monoamines and mRNA levels of enzymes of
      the melatonin synthesis and its noradrenergic regulation in pineal glands from 18
      controls, 33 preclinical AD subjects, and 25 definite AD patients. Pineal
      melatonin levels were highly correlated with cerebrospinal fluid melatonin
      levels. The circadian melatonin rhythm disappeared because of decreased nocturnal
      melatonin levels in both the preclinical AD and AD patients. Also the circadian
      rhythm of beta(1)-adrenergic receptor mRNA disappeared in both patient groups.
      The precursor of melatonin, serotonin was stepwise depleted during the course of
      AD, as indicated by the up-regulated monoamine oxidase A mRNA and activity (5
      hydroxyindoleacetic acid:serotonin ratio). We conclude that a dysfunction of
      noradrenergic regulation and the depletion of serotonin by increased monoamine
      oxidase A result in the loss of melatonin rhythm already in preclinical AD.

PMID- 14671189
TI  - Altered cortisol metabolism in polycystic ovary syndrome: insulin enhances 5alpha
      reduction but not the elevated adrenal steroid production rates.
AB  - Androgen excess in women with polycystic ovary syndrome (PCOS) may be ovarian
      and/or adrenal in origin, and one proposed contributing mechanism is altered
      cortisol metabolism. Increased peripheral metabolism of cortisol may occur by
      enhanced inactivation of cortisol by 5alpha-reductase (5alpha-R) or impaired
      reactivation of cortisol from cortisone by 11beta-hydroxysteroid dehydrogenase
      type 1 (11beta-HSD1) resulting in decreased negative feedback suppression of ACTH
      secretion maintaining normal plasma cortisol concentrations at the expense of
      androgen excess. We have tested whether any enzyme dysregulation was related to
      circulating insulin or androgen concentrations in women with PCOS and have sought
      to clarify their relationship with obesity. First, to avoid obesity-related
      effects on cortisol metabolism, 18 lean women with PCOS were compared with 19
      lean controls who were closely matched for body mass index (BMI). Second, the
      impact of obesity was studied in a cross-section of 42 PCOS women of a broad
      range of BMI. We measured 24-h urinary excretion of steroid metabolites by gas
      chromatography/mass spectrometry and fasting metabolic and hormone profiles.
      Urinary excretion of androgens [androsterone (P = 0.003), etiocholanolone (P =
      0.02), and C19 steroid sulfates (P = 0.009)], cortisone metabolites
      [tetrahydrocortisone (THE) (P = 0.02), alpha-cortolone (P < 0.001), beta-cortol +
      beta-cortolone (P < 0.001), cortolones (P < 0.001), and E metabolites (P <
      0.001)], and TCM (P = 0.002) were raised in lean PCOS subjects when compared with
      controls. A significantly higher 5alpha-tetrahydrocortisol (5alpha-THF)/5beta-THF
      ratio (P = 0.04) and a significantly lower alpha-THF + THF + alpha-cortol/THE +
      cortolones ratio (P = 0.01) were found in lean PCOS women compared with lean
      controls, indicating both enhanced 5alpha-R and reduced 11beta-HSD1 activities. A
      decreased THE/cortolones ratio (P = 0.03) was also found in lean PCOS women
      compared with lean controls, indicating increased 20 alpha/beta-HSD activity. In
      the group of 42 PCOS subjects, measures of 5alpha/5beta reduction were positively
      correlated with the homeostasis model insulin resistance index (HOMA-R): alpha
      THF/THF and HOMA-R (r = 0.34; P = 0.03), androsterone/etiocholanolone and HOMA-R
      (r = 0.32; P = 0.04), and total 5alpha /total 5beta and HOMA-R (r = 0.37; P =
      0.02). A positive correlation was also found between measures of 5alpha-R and BMI
      (r = 0.37; P = 0.02). No correlation was found between measures of 11beta-HSD1
      activity and indices of insulin sensitivity or BMI. We have demonstrated that
      there is an increased production rate of cortisol and androgens as measured in
      vivo in lean PCOS women. Insulin seems to enhance 5alpha reduction of steroids in
      PCOS but was not associated with the elevated cortisol production rate. The
      changes in 5alpha-R, 11beta-HSD1, and 20alpha/beta-HSD enzyme activities observed
      in PCOS may contribute to the increased production rates of cortisol and
      androgens, supporting the concept of a widespread dysregulation of steroid
      metabolism. This dysregulation does not seem to be the primary cause of PCOS
      because no correlation was found between serum androgen levels or urinary
      excretion of androgens with measurements of either 5alpha-R or 11beta-HSD1
      activities.

PMID- 14671190
TI  - The Trp(64)Arg polymorphism of the beta(3)-adrenergic receptor gene is not
      associated with body weight or body mass index in Japanese: a longitudinal
      analysis.
AB  - The beta(3)-adrenergic receptor (ADRB3) is expressed mainly in visceral adipose
      tissue and is thought to contribute to lipolysis and the delivery of free fatty
      acids to the portal vein. Although many studies have examined the relationship
      between the Trp(64)Arg mutation of ADRB3 and obesity, the results have been
      inconsistent. We examined the cross-sectional relationship of ADRB3 variants with
      indexes of obesity, and their longitudinal changes over 10 yr, in men and women,
      aged 40-69 yr, who were randomly selected from the Japanese rural population. The
      study considered both dietary energy intake and physical activity levels. Among
      the 746 participants, the genotype frequencies of the Trp(64)Trp, Trp(64)Arg, and
      Arg(64)Arg variants were 483, 224, and 39, respectively. The cross-sectional
      analysis showed no significant differences in height, weight, body mass index,
      blood pressure, serum total and high density lipoprotein cholesterols, and
      hemoglobin A(1c) among the genotype groups even after adjustments for gender,
      age, smoking, alcohol drinking, physical activity, and energy intake. No
      significant differences in the weight changes between the genotype groups were
      evident in the longitudinal analysis. We conclude that the Trp(64)Arg mutation of
      ADRB3 has little or no influence on either body weight or body mass index in the
      general Japanese population.

PMID- 14671191
TI  - Decreased fatty acid beta-oxidation in riboflavin-responsive, multiple
      acylcoenzyme A dehydrogenase-deficient patients is associated with an increase in
      uncoupling protein-3.
AB  - Riboflavin-responsive, multiple acylcoenzyme A dehydrogenase deficiency (RR-MAD),
      a lipid storage myopathy, is characterized by, among others, a decrease in fatty
      acid (FA) beta-oxidation capacity. Muscle uncoupling protein 3 (UCP3) is up
      regulated under conditions that either increase the levels of circulating free FA
      and/or decrease FA beta-oxidation. Using a relatively large cohort of seven RR
      MAD patients, we aimed to better characterize the metabolic disturbances of this
      disease and to explore the possibility that it might increase UCP3 expression. A
      battery of biochemical and molecular tests were performed, which demonstrated
      decreases in FA beta-oxidation and in the activities of respiratory chain
      complexes I and II. These metabolic alterations were associated with increases of
      3.1- and 1.7-fold in UCP3 mRNA and protein expression, respectively. All
      parameters were restored to control values after riboflavin treatment. We
      postulate that the up-regulation of UCP3 in RR-MAD is due to the accumulation of
      muscle FA/acylCoA. RR-MAD is an optimal model to support the hypothesis that UCP3
      is involved in the outward translocation of an excess of FA from the mitochondria
      and to show that, in humans, the effects of FA on UCP3 expression are direct and
      independent of fatty acid beta-oxidation.

PMID- 14671192
TI  - Genetic polymorphism PC-1 K121Q and ethnic susceptibility to insulin resistance.
AB  - Genetic susceptibility may be responsible for high prevalence of insulin
      resistance in Asian Indians. This study was carried out in samples of local Asian
      Indians and Caucasians to determine whether plasma cell membrane glycoprotein
      (PC)-1 K121Q and insulin receptor substrate-1 (IRS-1) G972A polymorphisms
      contribute significantly to susceptibility to insulin resistance in Asian
      Indians. The frequency of carrying at least one copy of the PC-1 121Q variant in
      Asian Indians was significantly higher than that in Caucasians (P = 0.01), but
      the frequency was similar for IRS-1 972A (6% and 7%). A significantly higher
      insulin area under the curve during oral glucose tolerance testing (P < 0.0001)
      and lower insulin sensitivity during hyperinsulinemic-euglycemic clamps (P =
      0.04) were found in Asian Indians with PC-1 121Q variant compared with Asian
      Indians with wild-type PC-1 and with Caucasians with or without the polymorphism.
      IRS-1 972A was not associated with any change in insulin sensitivity. We conclude
      that the PC-1 K121Q polymorphism associates with primary insulin resistance in
      migrant Asian Indians. A relatively high frequency of this polymorphism thus may
      be one factor contributing to insulin resistance susceptibility in Asian Indians.
      This finding indicates the need for expanded studies on the association between
      PC-1 K121Q and insulin resistance in a representative sample of the Asian Indian
      population.

PMID- 14671193
TI  - Genome-wide linkage scan for the metabolic syndrome in the HERITAGE Family Study.
AB  - The metabolic syndrome involves multiple and interactive effects of genes and
      environmental factors. To identify chromosomal regions encoding genes possibly
      predisposing to the metabolic syndrome, we performed a genome-wide scan with 456
      white and 217 black participants from 204 nuclear families of the HERITAGE Family
      Study, using regression-based, single- and multipoint linkage analyses on 509
      markers. A principal component analysis was performed on 7 metabolic syndrome
      related phenotypes. Two principal components, PC1 and PC2 (55% of the variance),
      were used as metabolic syndrome phenotypes. ANOVA was used to quantify the
      familial aggregation of PC1 and PC2. Family membership contributed significantly
      (P < 0.0023) to the variance in PC1 (r(2) = 0.38 in whites; r(2) = 0.55 in
      blacks) and PC2 (r(2) = 0.51; r(2) = 0.48). In whites, promising evidence for
      linkage (P < 0.0023) was found for PC1 (2 markers on 10p11.2) and PC2 (a marker
      on 19q13.4). Suggestive evidence of linkage (0.01 > P > 0.0023) appeared for PC1
      (1q41 and 9p13.1) and PC2 (2p22.3). In blacks, promising linkage was found for
      PC2 on 1p34.1, and suggestive linkage was found on 7q31.3 and 9q21.1. The genome
      wide scan revealed evidence for quantitative trait loci on chromosomal regions
      that have been previously linked with individual cardiovascular disease and type
      2 diabetes risk factors. Some of these chromosomal regions harbor promising
      potential candidate genes.

PMID- 14671194
TI  - Local androgen inactivation in abdominal visceral adipose tissue.
AB  - We examined the expression and activity of two enzymes from the aldoketoreductase
      (AKR) family 1C, namely type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD-5,
      AKR1C3) and type 3 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD-3, AKR1C2) in
      female sc and omental adipose tissue and in preadipocyte primary cultures. 17beta
      HSD-5 preferentially synthesizes testosterone from the inactive adrenal precursor
      androstenedione, whereas 3alpha-HSD-3 inactivates dihydrotestosterone. mRNAs of
      both enzymes were detected in adipose tissue from the omental and sc
      compartments. Real-time PCR quantification indicated a 3-fold higher 3alpha-HSD-3
      expression compared with 17beta-HSD-5, and the expression of both enzymes tended
      to be higher in the sc vs. the omental depot. Accordingly, dose-response and time
      course experiments performed in preadipocyte primary cultures indicated that
      3alpha-HSD activity was higher than 17beta-HSD activity (13-fold maximum velocity
      difference). We measured 3alpha-HSD activity in omental and sc adipose tissue
      samples of 32 women for whom body composition and body fat distribution were
      evaluated by dual-energy x-ray absorptiometry and CT, respectively. We found that
      androgen inactivation in omental adipose tissue through 3alpha-HSD activity was
      significantly higher in women with elevated vs. low visceral adipose tissue
      accumulation (1.7-fold difference; P < 0.05). Moreover, omental adipose tissue
      3alpha-HSD activity was positively and significantly associated with CT-measured
      visceral adipose tissue (r = 0.43; P < 0.02) and omental adipocyte diameter (r =
      0.42; P < 0.02). These results indicate that local androgen inactivation is a
      predominant reaction in female abdominal adipose tissue, with the greatest
      conversion rates observed in the presence of abdominal visceral obesity.
      Increased androgen inactivation in omental adipose tissue of abdominally obese
      women may impact locally on the regulation of adipocyte metabolism.

PMID- 14671195
TI  - Pharmacokinetics and dose finding of a potent aromatase inhibitor, aromasin
      (exemestane), in young males.
AB  - Suppression of estrogen, via estrogen receptor or aromatase blockade, is being
      investigated in the treatment of different conditions. Exemestane (Aromasin) is a
      potent and selective irreversible aromatase inhibitor. To characterize its
      suppression of estrogen and its pharmacokinetic (PK) properties in males, healthy
      eugonadal subjects (14-26 yr of age) were recruited. In a cross-over study, 12
      were randomly assigned to 25 and 50 mg exemestane daily, orally, for 10 d with a
      14-d washout period. Blood was withdrawn before and 24 h after the last dose of
      each treatment period. A PK study was performed (n = 10) using a 25-mg dose.
      Exemestane suppressed plasma estradiol comparably with either dose [25 mg, 38% (P
      <or= 0.002); 50 mg, 32% (P <or= 0.008)], with a reciprocal increase in
      testosterone concentrations (60% and 56%; P <or= 0.003 for both). Plasma lipids
      and IGF-I concentrations were unaffected by treatment. The PK properties of the
      25-mg dose showed the highest exemestane concentrations 1 h after administration,
      indicating rapid absorption. The terminal half-life was 8.9 h. Maximal estradiol
      suppression of 62 +/- 14% was observed at 12 h. The drug was well tolerated. In
      conclusion, exemestane is a potent aromatase inhibitor in men and an alternative
      to the choice of available inhibitors. Long-term efficacy and safety will need
      further study.

PMID- 14671196
TI  - Elevated serum level of anti-mullerian hormone in patients with polycystic ovary
      syndrome: relationship to the ovarian follicle excess and to the follicular
      arrest.
AB  - The serum level of anti-Mullerian hormone (AMH), a product from granulosa cells
      involved in follicle growth, has been shown to correlate tightly with the small
      antral follicle number (FN) at ultrasonography (U/S) in women who do not have
      polycystic ovary syndrome (PCOS). Because PCOS is associated with a 2- to 3-fold
      increase in growing FN, we investigated whether an increased AMH serum level
      correlates to other hormonal and/or U/S features of PCOS. Serum AMH has been
      assayed in 104 women (59 symptomatic PCOS, 45 controls) between d 2 and 7 after
      the last either spontaneous or progestin-induced (in PCOS) menstrual period. Mean
      serum AMH level was markedly increased in the PCOS group (47.1 +/- 22.9 vs. 20.8
      +/- 11.6 pmol/liter in controls; P < 0.0001), an increase in the same order of
      magnitude as the one of the FN in the 2- to 5-mm range at U/S (12.8 +/- 8.3 vs.
      4.8 +/- 1.9; P < 0.0001, respectively). The ratio AMH/FN was similar between the
      two groups (4.8 +/- 3.4 vs. 4.8 +/- 2.9; P = 0.55). By simple regression, both in
      PCOS and controls, the AMH level was positively related to the 2- to 5-mm FN at
      U/S (P < 0.0001 and P < 0.03, respectively), but not to the 6- to 9-mm FN, and
      was negatively correlated to the serum FSH level (P < 0.02 and P < 0.04,
      respectively). AMH was also positively related to the serum testosterone and
      androstenedione levels, in PCOS exclusively (P < 0.0005 and <0.002,
      respectively). No relationship was found between AMH and age, serum estradiol,
      inhibin B, and LH levels in both groups. After multiple regression only the 2- to
      5-mm FN remained significantly related to AMH in PCOS whereas testosterone,
      androstenedione, and FSH were no longer. In conclusion, the assay of the serum
      AMH may represent an important breakthrough in the diagnosis and in the
      understanding of PCOS. Our data suggest that the increase of AMH serum level in
      PCOS is the consequence of the androgen-induced excess in small antral FN and
      that each follicle produces a normal amount of AMH. We hypothesize that an
      increased AMH tone within the cohort could be involved in the follicular arrest
      of PCOS, by interacting negatively with FSH at the time of selection.

PMID- 14671197
TI  - Association of glutathione peroxidase activity with insulin resistance and
      dietary fat intake during normal pregnancy.
AB  - Glutathione peroxidase (GPx) is one of the most important antioxidant enzymes in
      humans. We studied the relationship between erythrocyte GPx activity and fasting
      serum insulin, plasma glucose, and C-peptide, estimates of insulin resistance
      from the homeostasis model of assessment as well as dietary fat intake in 408
      normotensive nondiabetic pregnant women from Camden, NJ. GPx activity and the
      metabolic parameters were determined at entry to care (16 wk of pregnancy) and
      during the third trimester. GPx activity and the levels of insulin resistance
      increased significantly between entry and the third trimester. Statistically
      significant associations, all positive, were observed between GPx activity and
      fasting insulin (beta = 0.009, P < 0.001), glucose (beta = 0.975, P < 0.05), C
      peptide (beta = 1.537, P < 0.01), and insulin resistance from the homeostasis
      model of assessment (beta = 0.209, P < 0.01). Dietary intakes of fat and
      polyunsaturated fatty acids were positively correlated with GPx activity as well.
      African Americans had significantly higher GPx activity, dietary fat, and
      polyunsaturated fatty acid intake than Hispanics and Caucasians. In conclusion,
      we demonstrated that normal pregnancy is associated with increased GPx activity
      and insulin resistance. There are ethnic differences in antioxidant response and
      dietary fat intake. Our findings suggest a potential link among antioxidant
      defenses, insulin resistance, and dietary fat intake.

PMID- 14671198
TI  - Defect in epinephrine production in children with craniopharyngioma: functional
      or organic origin?
AB  - Despite pituitary hormone replacement, patients with craniopharyngioma often
      complain of fatigue. They may have deficient control of catecholamine secretion
      caused by hypothalamic lesion. Another hypothesis is a functional defect in
      catecholamine production through either glucocorticoid deficiency because high
      intraadrenal glucocorticoid concentration is necessary for epinephrine synthesis
      or unrecognized hypoglycemia, which can intrinsically alter epinephrine
      secretion. We measured catecholamine response to insulin-induced hypoglycemia and
      orthostasis, and 24-h urinary catecholamine excretion, in 16 children with
      craniopharyngioma (patients) and 27 sex- and age-matched short children. We also
      studied the influence of a 4-fold increase in the usual daily dose of
      hydrocortisone on catecholamine excretion (50 vs. 12 mg/m(2) of body surface
      area) in the glucocorticoid-deficient patients. Last, we compared 24-h continuous
      sc glucose in patients and 10 sex- and age-matched healthy children. The results
      are expressed as medians (25th, 75th). For a similar blood glucose nadir after
      insulin administration, peak plasma epinephrine in response to hypoglycemia was
      lower in patients vs. controls [420 (120, 715) vs. 730 (460, 1200) ng/liter, P <
      0.01], whereas peak plasma norepinephrine was higher [390 (280, 550) vs. 270
      (180, 280) ng/liter, P < 0.05]. Catecholamine response to orthostasis did not
      differ between groups. Urinary epinephrine was significantly lower in patients (P
      < 0.001), whereas urinary norepinephrine was similar. The extent of epinephrine
      deficiency correlated with neither tumor size nor hypothalamic involvement. A 4
      fold higher hydrocortisone dose did not correct the defective epinephrine
      excretion in the glucocorticoid-deficient patients. Last, the 24-h sc glucose
      values were similar between patients and controls. In conclusion, children with
      craniopharyngioma have a defect in epinephrine but not norepinephrine production.
      There is no proof of a univocal origin, either organic or functional. Whether
      abnormal catecholamine secretion alters glucose level during fasting or acute
      illness, or hampers adaptation to exercise, requires further studies.

PMID- 14671199
TI  - Association of the (TAAAA)n repeat polymorphism in the sex hormone-binding
      globulin (SHBG) gene with polycystic ovary syndrome and relation to SHBG serum
      levels.
AB  - SHBG levels are frequently low in women with polycystic ovary syndrome (PCOS) and
      may contribute to increased tissue exposure to free androgens. A (TAAAA)n repeat
      polymorphism in the promoter of the SHBG gene has been described recently, and
      its transcriptional activity has been shown to be related to the number of tandem
      repeats. Recent evidence also suggests that prenatal exposure to androgen excess
      may program for the development of the PCOS phenotype during adulthood. Our aim
      was to investigate the possible association of the functional (TAAAA)n
      polymorphism in the promoter of the SHBG gene with PCOS and its relation to SHBG
      levels. We studied 185 women with PCOS and 324 normal controls. Genotype analysis
      revealed six (TAAAA)n alleles containing 6-11 repeats. The distribution of these
      alleles was different in the two groups. Women with PCOS had a significantly
      greater frequency of longer (TAAAA)n alleles (more than eight repeats) than
      normal women who had shorter alleles (less than eight repeats) in higher
      frequency (P = 0.001). Furthermore, in the PCOS group, carriers of the longer
      allele genotypes had lower SHBG levels [1.17 +/- 0.68 micro g/dl (35.1 +/- 20.5
      nmol/liter)] than those with shorter alleles [1.51 +/- 0.93 microg/dl (45.3 +/-
      28 nmol/liter P = 0.02). A novel (TAAAA)n allele, which has not been previously
      reported, was found in low frequency, mainly in the control population. From
      these results, there is evidence that there may be a genetic contribution to
      decreased SHBG levels frequently seen in women with PCOS. The SHBG gene may act
      as a susceptibility gene for PCOS and may provide the genetic link for the
      developmental origin hypothesis for PCOS that was recently proposed on the basis
      of experimental observation in prenatally androgenized sheep and primates.

PMID- 14671200
TI  - Cell proliferation activities on skin fibroblasts from a short child with absence
      of one copy of the type 1 insulin-like growth factor receptor (IGF1R) gene and a
      tall child with three copies of the IGF1R gene.
AB  - The type 1 IGF receptor (IGF1R) is required for normal embryonic and postnatal
      growth. The aim of this study was to determine whether we could detect abnormal
      IGF1R function in skin fibroblasts from children with an abnormal copy number of
      the IGF1R gene. We report two children with altered copy number of the IGF1R gene
      who presented with abnormal growth. Case 1 is a girl with intrauterine growth
      retardation, postnatal growth failure, and recurrent hypoglycemia. Pituitary
      function tests were normal. Routine karyotype analysis identified a deletion on
      15q26.2, and a fluorescence in situ hybridization study using IGF1R probes showed
      only a single IGF1R gene. Case 2 was large for gestational age, with birth weight
      and length at or above 97th percentile, and showed rapid early postnatal growth.
      He was found to have a recombinant chromosome 15 containing a partial duplication
      at 15q (q25-qter). A fluorescence in situ hybridization study using the same
      probes showed three copies of the IGF1R gene. In a mitochondrial activity assay,
      skin fibroblasts from the subject with only one copy of IGF1R showed slower
      growth, whereas cells from the subject with three copies of IGF1R showed
      accelerated growth compared with controls. IGF1R phosphorylation, as assessed by
      Western blot, and IGF1R binding studies were decreased compared with controls in
      the child with one copy of the IGF1R and increased in the child with three copies
      of the gene. Our data are consistent with the concept that IGF1R gene copy number
      is of functional and clinical importance in humans.

PMID- 14671201
TI  - No influence of melatonin on cerebral blood flow in humans.
AB  - Melatonin has been attributed a role in a number of physiological processes.
      Changes in distal skin temperature and blood pressure after intake of melatonin
      suggest that melatonin induces peripheral vasodilation. The effect on the
      cerebral blood flow is still unknown. We examined the effect of a single pulse of
      melatonin on cerebral and peripheral blood flow, using the latter as a positive
      control. Ten male healthy volunteers (mean age, 22 +/- 3.2 yr) participated in a
      double-blind, randomized, placebo-controlled, cross-over study. On one occasion
      10 microg melatonin were infused i.v., and on the other occasion saline was
      infused as the matching placebo. Cerebral blood flow was measured using phase
      contrast magnetic resonance imaging. Peripheral blood flow was determined from
      changes in the distal to proximal skin temperature gradient and finger pulse
      volume. Serum melatonin concentration increased from 12 +/- 5 pg/ml at baseline
      to 487 +/- 377 pg/ml at 5 min and 156 +/- 68 pg/ml at 10 min after melatonin
      administration. There was no significantly different time course for cerebral
      blood flow and cerebrovascular resistance. Compared with placebo, melatonin
      significantly increased peripheral blood flow, as measured by distal to proximal
      skin temperature gradient and finger pulse volume. These data demonstrate that
      melatonin does not have an acute regulatory effect on cerebral blood flow in
      humans.

PMID- 14671202
TI  - Endothelial cells and peripheral blood mononuclear cells are a potential source
      of extraplacental activin a in preeclampsia.
AB  - An excessive systemic inflammatory response, involving endothelial cells and
      leukocytes, underlies the maternal symptoms of preeclampsia. Activin A is raised
      in preeclampsia, suggesting a possible involvement in its pathophysiology. The
      placenta is the main source of activin A in normal pregnancy. We investigated
      whether peripheral blood mononuclear cells (PBMCs) and endothelium, activated by
      proinflammatory stimuli, were a potential source of activin A in preeclampsia.
      Both endotoxin and TNFalpha stimulated activin A secretion by PBMCs from
      nonpregnant, preeclamptic, and matched normal pregnant women (P < 0.05).
      Pregnancy increased the responsiveness of PBMCs to endotoxin (P < 0.05), whereas
      only the preeclamptic group were significantly more responsive to TNFalpha (P <
      0.05). Human umbilical vein endothelial cells secreted activin A spontaneously
      and in response to TNFalpha (P < 0.05), but recombinant IL-1beta and IL-6 had no
      significant effect over the 72-h culture period. Inhibin A and follistatin were
      undetectable (<2 pg/ml and < 20 pg/ml, respectively) in PBMCs and human umbilical
      vein endothelial cell culture media. These data suggest that PBMCs and
      endothelium, activated by TNFalpha, could be extraplacental sources of activin A
      in preeclampsia. The pathological significance of increased activin A in
      preeclampsia is unknown, although it may have a role in the mechanisms underlying
      endothelium dysfunction.

PMID- 14671203
TI  - Characterization of a circulating N-extended form of the thyrotropin-releasing
      hormone-like peptide pGlu-Glu-Pro amide in human plasma.
AB  - The TRH-like peptides pGlu-Glu-Pro amide, pGlu-Phe-Pro amide, and pGlu-Gln-Pro
      amide were isolated and identified some years ago, and these peptides have been
      proven to be present in many tissues and fluids. The presence of TRH-like
      immunoreactivity distinct from TRH in blood has been observed previously. In the
      present study, the presence of N-extended forms of TRH-like peptides in plasma
      has been investigated. Peripheral blood samples of human, rat, and rabbit were
      obtained and plasma was extracted. The peptides were separated in several steps
      of chromatography, including gel filtration, cation and anion exchange, and HPLC.
      The concentrations of the TRH-like peptides in the column fractions were measured
      by RIA with TRH antibody. The N-extended forms of TRH-like peptides were
      determined by RIA after trypsin digestion. In human plasma it was observed an N
      extended form of TRH-like peptides in substantial concentration. After trypsin
      and heating, the N-extended forms of TRH-like peptides were rechromatographed on
      Sephadex G-50. This showed that the TRH-like peptides released have a similar
      size to TRH. The peptides were then separated by cation exchange chromatography,
      and the major fraction was unretained, indicating a neutral or acidic nature.
      Part of the unretained fraction was then chromatographed on anion exchange column
      in which the major fraction was retained, demonstrating the acidic nature of the
      peptides. Similar results have been observed in rat and rabbit. The other part of
      the unretained fraction from cation exchange chromatography of human plasma was
      purified on HPLC. The results demonstrated that the major component observed by
      HPLC cochromatographed with synthetic pGlu-Glu-Pro amide. This study represents
      the first demonstration of a circulating N-extended form of any TRH-like peptide.

PMID- 14671205
TI  - Water-induced thermogenesis.
AB  - Drinking lots of water is commonly espoused in weight loss regimens and is
      regarded as healthy; however, few systematic studies address this notion. In 14
      healthy, normal-weight subjects (seven men and seven women), we assessed the
      effect of drinking 500 ml of water on energy expenditure and substrate oxidation
      rates by using whole-room indirect calorimetry. The effect of water drinking on
      adipose tissue metabolism was assessed with the microdialysis technique. Drinking
      500 ml of water increased metabolic rate by 30%. The increase occurred within 10
      min and reached a maximum after 30-40 min. The total thermogenic response was
      about 100 kJ. About 40% of the thermogenic effect originated from warming the
      water from 22 to 37 C. In men, lipids mainly fueled the increase in metabolic
      rate. In contrast, in women carbohydrates were mainly used as the energy source.
      The increase in energy expenditure with water was diminished with systemic beta
      adrenoreceptor blockade. Thus, drinking 2 liters of water per day would augment
      energy expenditure by approximately 400 kJ. Therefore, the thermogenic effect of
      water should be considered when estimating energy expenditure, particularly
      during weight loss programs.

PMID- 14671204
TI  - Glucocorticoids and insulin sensitivity: dissociation of insulin's metabolic and
      vascular actions.
AB  - Insulin sensitivity in tissues such as a skeletal muscle and fat is closely
      correlated with insulin action in the vasculature, but the mechanism underlying
      this is unclear. We investigated the effect of dexamethasone on insulin
      stimulated glucose disposal and vasodilation in healthy males to test the
      hypothesis that a reduction in glucose disposal would be accompanied by a
      reduction in insulin action in the vasculature. We performed a double-blind,
      placebo-controlled, cross-over trial comparing insulin sensitivity (measured by
      the euglycemic hyperinsulinemic clamp) and vascular insulin action (measured by
      small vessel wire myography) in young healthy males allocated to placebo or 1 mg
      dexamethasone twice daily for 6 d, each in random order. Six days of
      dexamethasone therapy was associated with a 30% (95% confidence interval, 19.1
      40.0%) fall in insulin sensitivity. Despite this, there was no difference in
      insulin-mediated vasodilation between phases. Dexamethasone had no effect on
      circulating markers of endothelial function, such as D-dimer, von Willebrand
      factor, and tissue plasminogen activator. By short-term exposure to high dose
      dexamethasone we were able to differentially affect the metabolic and vascular
      actions of insulin. This implies that, using this model, there is physiological
      uncoupling of the effects of insulin in different tissues.

PMID- 14671206
TI  - The role of the orphan nuclear receptor, liver receptor homologue-1, in the
      regulation of human corpus luteum 3beta-hydroxysteroid dehydrogenase type II.
AB  - After ovulation, ovarian 3beta-hydroxysteroid dehydrogenase type II (HSD3B2)
      expression increases to enhance the shift of steroidogenesis toward progesterone
      biosynthesis. Steroidogenic factor-1 (SF-1) is a transcription factor for several
      genes encoding steroidogenic enzymes. However, the level of SF-1 expression
      decreases in the human corpus luteum (CL) after ovulation. Liver receptor homolog
      1 (LRH-1) is another member of the orphan nuclear receptor family. We hypothesize
      that LRH-1, rather than SF-1, plays an essential role in the regulation of corpus
      luteum steroidogenesis. Semiquantitative RT-PCR and real-time PCR were performed
      to quantify the level of LRH-1 expression and correlate with HSD3B2 level. Cell
      transfection, mutation analysis, and EMSA were performed to examine the role of
      LRH-1 in the regulation of HSD3B2. LRH-1 expression was higher in CL, compared
      with mature ovarian follicles. Cotransfection of granulosa cells with HSD3B2 and
      LRH-1 resulted in a 10-fold increase of transcription. DAX-1 inhibited LRH-1
      stimulated HSD3B2, which was maintained in the presence of dibutyryl cAMP.
      Mutation of the either of the two putative LRH-1 binding sites, which were
      confirmed by EMSA, in the HSD3B2 promoter decreased LRH-1 stimulation. Our
      findings suggest that LRH-1 is highly expressed in CL, and it plays an essential
      role in the regulation of HSD3B2.

PMID- 14671207
TI  - Platelet-activating factor inhibits the secretion of platelet-activating factor
      acetylhydrolase by human decidual macrophages.
AB  - To clarify the role of platelet-activating factor (PAF) in parturition, the
      effects of PAF on the secretion of PAF-acetylhydrolase (PAF-AH), a PAF
      inactivating enzyme, by decidual macrophage populations were examined. The cells
      were isolated from human decidual tissue by enzymatic digestion, Ficoll-Paque
      centrifugation, or flow cytometric sorting. The nonhydrolyzable agonist of PAF,
      carbamyl-PAF (C-PAF), inhibited the secretion of PAF-AH by either decidual cells
      or flow cytometrically purified decidual macrophages. A specific PAF receptor
      antagonist, WEB 2086, blocked the C-PAF-induced inhibition. Lyso-PAF, a
      metabolite of PAF, had no effect on the enzyme secretion. An intracellular
      calcium channel blocker, bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid,
      tetra(acetoxymethyl)-ester, partially blocked the inhibition by C-PAF, whereas
      extracellular calcium channel blockers, nifedipine and verapamil, were without
      effect. The inhibitory effect of C-PAF was also partially blocked by protein
      kinase C (PKC) inhibitors, sphingosine and H-7. A PKC activator, 12-O
      tetradecanoylphobol 13-acetate, decreased the secretion of PAF-AH. The decrease
      was abolished by the addition of sphingosine and H-7. It is suggested that PAF
      inhibits the PAF-AH secretion by decidual macrophages and that the inhibitory
      action is mediated by a signal transduction mechanism involving intracellular
      calcium and PKC.

PMID- 14671208
TI  - Mutational analysis of the FOXP3 gene and evidence for genetic heterogeneity in
      the immunodysregulation, polyendocrinopathy, enteropathy syndrome.
AB  - The immunodysregulation, polyendocrinopathy, enteropathy syndrome (IPEX), is a
      rare disorder of immune regulation resulting in multiple autoimmune disorders,
      which demonstrates X-linked recessive inheritance. The disease gene, FOXP3, was
      identified in 2001, and several mutations within this gene have since been
      described in patients with IPEX. We used linkage analysis, mutational screening
      of the FOXP3 gene, human leukocyte antigen typing, and analysis of X-chromosome
      inactivation to investigate 2 kindreds (21 subjects in total) with 4 male infants
      (3 now deceased) and 1 girl affected by IPEX. In 1 family a novel FOXP3 mutation
      was identified in the proband, with a single base deletion at codon 76 of exon 2,
      leading to a frameshift, which predicted a truncated protein product (108
      residues vs. 431 in wild type). In the second family, the FOXP3 locus was
      excluded by recombination, and mutational analysis of the gene was negative. The
      affected girl from this family was shown to have human leukocyte antigen DR2 and
      DR6 alleles and random X-chromosome inactivation in peripheral blood mononuclear
      cells. Our analysis has elucidated the molecular basis of IPEX in one family and
      has, for the first time, provided evidence for an autosomal locus, suggesting
      genetic heterogeneity in this syndrome.

PMID- 14671209
TI  - Differential expression and regulation of microsomal prostaglandin E(2) synthase
      in human fetal membranes and placenta with infection and in cultured trophoblast
      cells.
AB  - We have evaluated the effect of chorioamnionitis on the protein expression of
      microsomal and cytosolic prostaglandin E(2) synthases (mPGES and cPGES) in
      preterm human placentae (PL) and fetal membranes (FM), by Western blot and
      immunohistochemistry, as well as the regulatory effect of IL-1beta and TNF-alpha
      on mPGES, cPGES, and cyclooxygenase (COX)-2 expression in villous trophoblast
      (VT) and chorion trophoblast (CT) cell cultures. mPGES localized to the
      syncytiotrophoblast and vascular endothelium in PL and to the amnion epithelium,
      CT, and decidual cells in FM. cPGES protein was localized only to the
      syncytiotrophoblast in PL and had the same profile of expression as mPGES in FM.
      With infection, there was an increase in mPGES expression in PL and a decrease in
      the expression in FM. cPGES protein did not change in either PL or FM with
      infection. In VT cells in culture, IL-1beta up-regulated COX-2 protein expression
      but did not affect mPGES. However, TNF-alpha increased both mPGES and COX-2
      protein expression in these cells. In CT cells in culture, IL-1beta and TNF-alpha
      increased both mPGES and COX-2 protein levels. Neither IL-1beta nor TNF-alpha
      affected cPGES in either VT or CT cells. We conclude that protein levels of
      mPGES, as well as COX-2, can be stimulated by cytokines, potentially contributing
      to the increased prostaglandin production at the time of infection-driven preterm
      labor. However, multiple mechanisms, which apparently are inductor- and cell-type
      specific, exist for the regulation of these enzymes.

PMID- 14671210
TI  - Adrenomedullin messenger ribonucleic acid expression in the placentae of normal
      and preeclamptic pregnancies.
AB  - In pathological pregnancies, alterations in circulating maternal and fetal
      adrenomedullin (ADM) concentrations may mediate compensatory vascular responses
      in the fetal or placental circulation. To address whether ADM is a potential
      paracrine vasoactive factor within the placenta, the regional distribution and
      cellular localization of ADM mRNA expression were determined by Northern blot and
      in situ hybridization of different regions of the placenta and fetal membranes
      from pregnancies complicated by severe preeclampsia [<28 wk (n = 7) and >28 wk (n
      = 13)] and from normotensive pregnancies [<28 wk (n = 6) and >28 wk (n = 15)].
      Northern blotting revealed that ADM mRNA (1.3 kb) was expressed in chorionic
      villi and basal plate regions, but was most abundantly expressed in the
      choriodecidua. By in situ hybridization, ADM mRNA was localized to the
      syncytiotrophoblasts and the extravillous cytotrophoblasts in the basal plate and
      choriodecidua regions. ADM mRNA expression was increased in the choriodecidua,
      syncytial knots, and cytotrophoblasts in peri-infarct regions in preeclampsia. In
      chorionic villous explant studies maintained at reduced oxygen tension, ADM mRNA
      abundance was increased at 12, 24, and 48 h. ADM mRNA expressed in
      syncytiotrophoblasts and cytotrophoblasts in the basal plate decidua and
      choriodecidua may contribute to the maternal and fetal plasma levels. In
      preeclampsia, regional increases in ADM mRNA may be induced by hypoxia and
      mediate local fetal/placental adaptive responses to reduced placental perfusion.

PMID- 14671211
TI  - The lipid droplet-associated protein adipophilin is expressed in human
      trophoblasts and is regulated by peroxisomal proliferator-activated receptor
      gamma/retinoid X receptor.
AB  - Uptake and transplacental transfer of fatty acids is essential for fetal
      development. Human adipophilin and its murine ortholog adipocyte differentiation
      related protein are lipid droplet-associated proteins that are implicated in
      cellular fatty acid uptake in adipocytes. The nuclear receptor peroxisome
      proliferator-activated receptor-gamma (PPARgamma) stimulates lipid uptake by
      adipocytes and enhances differentiation of placental trophoblasts. We therefore
      hypothesized that adipophilin is expressed in human trophoblasts and that its
      expression is regulated by PPARgamma. We initially determined that adipophilin is
      expressed in human villous trophoblasts and that adipophilin expression is
      enhanced during differentiation of cultured primary term human trophoblasts. We
      also found that exposure of cultured human trophoblasts to the PPARgamma ligand
      troglitazone resulted in a concentration-dependent increase in adipophilin
      expression. We observed a similar increase with LG268, a ligand for retinoid X
      receptor (RXR), the heterodimeric partner of PPARgamma. Lastly, we demonstrated
      that ligand-activated PPARgamma and RXR stimulated the transcriptional activity
      of adipophilin promoter in CV-1 cells and in the placental JEG3 cell line. We
      conclude that the expression of adipophilin is enhanced during trophoblast
      differentiation and is up-regulated by ligand-activated PPARgamma/RXR. Enhanced
      adipophilin expression may contribute to fatty acid uptake by the placenta.

PMID- 14671212
TI  - Identification and characterization of extracellular matrix metalloproteinase
      inducer in human endometrium during the menstrual cycle in vivo and in vitro.
AB  - Extracellular matrix metalloproteinase inducer (EMMPRIN) participates in the
      breakdown of the extracellular matrix (ECM) by augmenting matrix
      metalloproteinase (MMP) expression. In the present study, we identified and
      characterized the menstrual cycle-dependent expression of EMMPRIN in human
      endometrium in vivo. At the proliferative phase of the menstrual cycle, EMMPRIN
      was detected in glandular epithelium of the basal layer in endometrium. In
      addition, at the superficial region of the functional layer, EMMPRIN was
      expressed in stroma but not glandular epithelium. At the secretory phase, EMMPRIN
      was found in both stroma and glandular epithelium of the functional layer and
      glandular epithelium of the basal layer. Furthermore, EMMPRIN colocalized with
      MMP-1/collagenase-1 in the glandular epithelium in vivo. Western blot analysis of
      tissue from the functional layer showed that EMMPRIN species with molecular
      weights of approximately 35 and 47 kDa were detected at the proliferative phase,
      whereas approximately 35- and 51-kDa EMMPRIN species were predominantly expressed
      at the secretory phase. In addition, the variant EMMPRIN molecules were found to
      differ in glycosylation. On the other hand, EMMPRIN was constitutively produced
      in primary cultured endometrial stromal and glandular epithelial cells. The
      production and glycosylation of EMMPRIN in the stromal cells were augmented by
      progesterone at the posttranscriptional and posttranslational stages,
      respectively. These results suggest for the first time that EMMPRIN is expressed
      in human endometrium during the menstrual cycle and that its expression and
      glycosylation are augmented by progesterone. Moreover, EMMPRIN may be involved in
      ECM breakdown at the interface between endometrial cells and ECM by using EMMPRIN
      bound MMP-1.

PMID- 14671213
TI  - In vivo phosphorylation of the somatostatin 2A receptor in human tumors.
AB  - Hormone-stimulated receptor internalization and desensitization occur widely in
      the G protein-coupled receptor (GPCR) family. A critical first step in both these
      processes is thought to be receptor phosphorylation, a reaction which has been
      extensively characterized in cell culture. However, little is known about GPCR
      phosphorylation in vivo. The somatostatin (SS) receptor subtype (sst)2A is widely
      distributed in human neuroendocrine tumors, and SS analogs are commonly used to
      target this receptor for both therapy and diagnosis. In cultured pituitary cells
      sst2A is rapidly phosphorylated and internalized after hormone binding. The aim
      of the present study was to go one crucial step further and characterize the
      phosphorylation state of this receptor in human neuroendocrine tumors using a
      newly developed gel-shift assay. The receptor from a somatostatinoma was
      completely phosphorylated. In contrast, only unphosphorylated sst2A was present
      in human tumors that were not exposed to autocrine stimulation. Both in vivo and
      in cultured cells, the phosphorylation state of the sst2A receptor was correlated
      with its subcellular localization: phosphorylated receptor was mostly
      intracellular, whereas unphosphorylated receptor was localized at the cell
      surface. These results are the first to demonstrate ligand-stimulated GPCR
      phosphorylation in human tissue in situ, providing a crucial step toward a better
      understanding of receptor regulation in vivo. Analysis of sst2A phosphorylation
      promises to provide a sensitive indicator of the effectiveness of SS analogs in
      diagnostic and therapeutic situations in tumor patients.

PMID- 14671214
TI  - Identification of adrenocorticotropin receptor messenger ribonucleic acid in the
      human pituitary and its loss of expression in pituitary adenomas.
AB  - The ACTH receptor (ACTH-R) is the second member of the melanocortin (MC-2)
      receptor family that includes five seven-transmembrane G protein-coupled
      receptors and has been shown to be predominantly expressed in the adrenal cortex.
      It has been postulated that ACTH may regulate its own secretion through ultra
      short-loop feedback within the pituitary. ACTH-secreting adenomas are
      characterized by resistance to glucocorticoid feedback, and they may have
      dysregulated ACTH feedback. We therefore investigated the ACTH-R in normal and
      adenomatous human pituitary tissue. We report here the identification of ACTH-R
      mRNA in the human pituitary gland, which was confirmed by direct sequencing. We
      studied the expression of the ACTH-R in 23 normal pituitary specimens and 53
      pituitary adenomas (22 ACTH-secreting, nine GH-secreting, eight prolactin
      secreting, one TSH-secreting, one FSH-secreting, 10 nonfunctioning, and two
      silent corticotroph adenomas), using the sensitive technique of real-time
      quantitative PCR. Contamination of ACTH-secreting adenomas and nonfunctioning
      pituitary adenomas with nonadenomatous tissue was excluded by lack of Pit-1
      expression. ACTH-R mRNA was detected in all normal pituitary specimens, and in
      situ hybridization colocalized expression to ACTH staining cells only. However,
      ACTH-R mRNA levels were undetectable in 16 of 22 ACTH-secreting tumors and in
      both silent corticotroph tumors. Diagnostic preoperative plasma ACTH levels were
      significantly lower in the ACTH-R positive ACTH-secreting tumors, compared with
      those who were ACTH-R negative (P = 0.0006). Direct sequencing of the coding
      region of the ACTH-R in cDNA from three ACTH-secreting tumors positively
      expressing the receptor showed no mutations, as did sequencing of genomic DNA in
      three receptor negative ACTH-secreting tumors and the two silent corticotrophs.
      These results provide further evidence compatible with an ACTH feedback loop in
      the pituitary and suggest that loss of expression of the ACTH-R in corticotroph
      adenomas of patients with Cushing's disease may play a role in the resistance to
      feedback of the pituitary-adrenal axis seen in these patients.

PMID- 14671215
TI  - Effects of chemotherapeutic agents on the function of primary human osteoblast
      like cells derived from children.
AB  - Studies in children treated with chemotherapy suggest that chemotherapeutic
      agents have deleterious effects on bone metabolism. We therefore evaluated the in
      vitro effects of clinically relevant concentrations of chemotherapeutic agents on
      the synthesis of type I collagen, alkaline phosphatase (AP) activity, and
      mineralization by primary human osteoblast-like (HOB) cells derived from
      children. Because serum 1,25-dihydroxyvitamin D(3) concentrations may be reduced
      during treatment with chemotherapy, the effect of chemotherapeutic agents on HOB
      cells cultured in the presence or absence of 1,25-dihydroxyvitamin D(3) was also
      evaluated. Type I collagen synthesis was reduced by all agents (P < 0.01) other
      than methotrexate, whereas the relative AP activity was increased (P < 0.01) by
      all agents. The relative number of cells staining intensely for AP after culture
      with agents increased (P < 0.05), and AP mRNA expression was increased (P < 0.01)
      with vincristine. 1,25-Dihydroxyvitamin D(3) ameliorated (P < 0.01) the depletion
      of HOB cell numbers by chemotherapeutic agents. Furthermore, vincristine and
      daunorubicin inhibited 1,25-dihydroxyvitamin D(3)-mediated AP activity (P <
      0.01). We conclude that chemotherapeutic agents can adversely affect HOB cell
      function, and we speculate that this observation may account, in part, for the
      osteopenia observed during and after treatment of children with chemotherapy.

PMID- 14671216
TI  - Resistin and type 2 diabetes: regulation of resistin expression by insulin and
      rosiglitazone and the effects of recombinant resistin on lipid and glucose
      metabolism in human differentiated adipocytes.
AB  - Resistin, an adipocyte secreted factor, has been suggested to link obesity with
      type 2 diabetes in rodent models, but its relevance to human diabetes remains
      uncertain. Although previous studies have suggested a role for this adipocytokine
      as a pathogenic factor, its functional effects, regulation by insulin, and
      alteration of serum resistin concentration by diabetes status remain to be
      elucidated. Therefore, the aims of this study were to analyze serum resistin
      concentrations in type 2 diabetic subjects; to determine the in vitro effects of
      insulin and rosiglitazone (RSG) on the regulation of resistin, and to examine the
      functional effects of recombinant human resistin on glucose and lipid metabolism
      in vitro. Serum concentrations of resistin were analyzed in 45 type 2 diabetic
      subjects and 34 nondiabetic subjects. Subcutaneous human adipocytes were
      incubated in vitro with insulin, RSG, and insulin in combination with RSG to
      examine effects on resistin secretion. Serum resistin was increased by
      approximately 20% in type 2 diabetic subjects compared with nondiabetic subjects
      (P = 0.004) correlating with C-reactive protein. No other parameters, including
      adiposity and fasting insulin levels, correlated with serum resistin in this
      cohort. However, in vitro, insulin stimulated resistin protein secretion in a
      concentration-dependent manner in adipocytes [control, 1215 +/- 87 pg/ml (mean +/
      SEM); 1 nM insulin, 1414.0 +/- 89 pg/ml; 1 microM insulin, 1797 +/- 107 pg/ml (P
      < 0.001)]. RSG (10 nM) reduced the insulin-mediated rise in resistin protein
      secretion (1 nM insulin plus RSG, 971 +/- 35 pg/ml; insulin, 1 microM insulin
      plus RSG, 1019 +/- 28 pg/ml; P < 0.01 vs. insulin alone). Glucose uptake was
      reduced after treatment with 10 ng/ml recombinant resistin and higher
      concentrations (P < 0.05). Our in vitro studies demonstrated a small, but
      significant, reduction in glucose uptake with human recombinant resistin in
      differentiated preadipocytes. In human abdominal sc adipocytes, RSG blocks the
      insulin-mediated release of resistin secretion in vitro. In conclusion, elevated
      serum resistin in human diabetes reflects the subclinical inflammation prevalent
      in type 2 diabetes. Our in vitro studies suggest a modest effect of resistin in
      reducing glucose uptake, and suppression of resistin expression may contribute to
      the insulin-sensitizing and glucose-lowering actions of the thiazolidinediones.

PMID- 14671217
TI  - Unexpected effects of epitope and chimeric tags on gonadotropin-releasing hormone
      receptors: implications for understanding the molecular etiology of
      hypogonadotropic hypogonadism.
AB  - In the case of human GnRH receptor (GnRHR) mutants associated with
      hypogonadotropic hypogonadism, a view emerged that these mutants are correctly
      routed to the plasma membrane. This view, supported almost entirely by studies
      using the HA-tag (hemagglutinin influenza virus epitope tag) and other epitope
      and chimeric tags, obscured recognition that GnRHR mutants frequently become
      misrouted proteins. The underlying assumption in epitope and chimeric tagging
      studies is that the cell does not distinguish tagged from unmodified proteins. It
      should not have been surprising, in retrospect, to find that even a single amino
      acid mutation dramatically alters protein function or routing because increased
      plasma membrane expression is associated with deletion of a single amino acid in
      the human GnRHR (K191), and point mutations have been shown to block plasma
      membrane routing of many receptors, including most of those responsible for the
      hypogonadotropic hypogonadism phenotype. Our present observations suggest that
      epitope and chimeric tags do have a significant effect on protein localization
      and function. Although rarely provided, control experiments addressing the
      effects of epitope or chimeric tagging are an essential part of any study relying
      on these proteomic tools.

PMID- 14671218
TI  - Radioiodine treatment of Graves' hyperthyroidism.

PMID- 14671219
TI  - Pretreatment with a single, low dose of recombinant human thyrotropin allows dose
      reduction of radioiodine therapy in patients with nodular goiter.

PMID- 14671222
TI  - The value of the low-dose dexamethasone suppression test in the differential
      diagnosis of hyperandrogenism in women.

PMID- 14671223
TI  - Crossing the cancer cell membrane to improve clinical outcomes.

PMID- 14671224
TI  - Signal events: Cell signal transduction and its inhibition in cancer.
AB  - Signal transduction refers to communication processes used by regulatory
      molecules to mediate the essential cell processes of growth, differentiation, and
      survival. Signal transduction elements interact through complex biochemically
      related networks. Aberrations in signal transduction elements can lead to
      increased proliferative potential, sustained angiogenesis, tissue invasion and
      metastasis, and apoptosis inhibition. Most human neoplasms have aberrant signal
      transduction elements. Several compounds that target aberrant signal transduction
      elements, such as those in the ErbB family of tyrosine kinase receptors and
      mammalian target of rapamycin, are in development. To date, commercially
      available signal-transduction-targeting compounds include trastuzumab, a
      monoclonal antibody against the ErbB-2 receptor for the treatment of metastatic
      breast cancer overexpressing the ErbB-2 (HER-2) receptor, and gefitinib, an
      inhibitor of the ErbB-1 receptor tyrosine kinase that recently received
      regulatory approval for the treatment of patients with non-small cell lung
      cancer. In contrast to traditional cytotoxic treatments, although signal
      transduction inhibitors are capable of inducing tumor regression, particularly in
      malignancies that are principally driven by specific target aberrations,
      preclinical and early clinical investigations suggest that their predominant
      beneficial effects are growth inhibitory in nature; therefore, new clinical trial
      designs and evaluation end points may be required to ultimately assess their
      value. Prospective profiling of patients and tumors to determine treatment
      response is also essential to the success of these clinical trials. However,
      responsiveness to these novel therapies is dependent on a multitude of factors
      that ultimately determine the robustness and quality of the downstream response.

PMID- 14671225
TI  - New insights into erythropoietin and epoetin alfa: mechanisms of action, target
      tissues, and clinical applications.
AB  - Recombinant human erythropoietin (epoetin alfa) has proven beneficial for the
      treatment of various anemias. The mechanism of action of endogenous
      erythropoietin and the therapeutic use of epoetin alfa to stimulate red blood
      cell production and improve the quality of life in cancer patients are reviewed
      here. Epoetin alfa may also attenuate the cognitive dysfunction associated with
      cancer therapy. Interestingly, functional endogenous erythropoietin receptor
      signaling pathways have been demonstrated in numerous nonerythropoietic tissues.
      Of particular importance, epoetin alfa confers neurotrophic and neuroprotective
      effects in cultured neurons and in several animal models for neurologic disease.
      In one clinical trial, epoetin alfa appeared to limit functional and histologic
      damage in patients with stroke. Therefore, in cancer patients receiving
      chemotherapy, the beneficial effects of epoetin alfa could be mediated not only
      through enhanced erythrocyte production but also via direct effects on the
      nervous system. Further investigation into the nonerythropoietic effects of
      epoetin alfa could broaden its clinical utility for patients with cancer and also
      provide new therapies for various neurologic disorders.

PMID- 14671226
TI  - Blocked pathways: FTIs shut down oncogene signals.
AB  - Ras proteins play fundamental roles in cell signal transduction pathways that
      regulate cell growth, differentiation, proliferation, and survival. ras mutations
      are among the most frequently encountered genetic abnormalities in human cancers
      and play a key role in tumorigenesis. The enzymatic attachment of a 15- or 20
      carbon moiety to the Ras protein through farnesylation or geranylgeranylation,
      respectively, is a required step in the proper localization and activation of
      Ras. Inhibition of the catalytic enzymes, farnesyl transferase and geranylgeranyl
      transferase, is a novel, mechanism-based, targeted approach to cancer therapy
      development. Geranylgeranyl transferase inhibitors suppress tumor growth by
      accumulating cells in the G(1)/S cell cycle phase. One mechanism by which
      farnesyl transferase inhibitors suppress tumor growth is by inhibiting bipolar
      spindle formation, thereby blocking progression from prophase to metaphase.
      Although the exact molecular target responsible for the antitumor activity of
      farnesyl transferase inhibitors is unclear, at least in some tumor cells,
      inhibition of phosphoinositide-3-OH kinase/Akt-mediated cell survival pathways
      may play a critical role. Identifying the farnesylated proteins that are targeted
      by farnesyl transferase inhibitors and the tumor molecular signatures that
      dictate which set of patients will respond to farnesyl transferase inhibitors are
      critical end points for future mechanistic studies.

PMID- 14671227
TI  - Modifications to therapy for multiple myeloma: pegylated liposomal Doxorubicin in
      combination with vincristine, reduced-dose dexamethasone, and thalidomide.
AB  - The combination of vincristine, doxorubicin, and dexamethasone is an effective
      treatment for multiple myeloma that produces a more rapid response than other
      regimens, probably a function of the high-dose, intense steroid schedule.
      However, vincristine/doxorubicin/dexamethasone administration requires a 96-hour
      continuous infusion delivered via a central venous catheter, which necessitates
      hospitalization in a large number of patients and may increase the risk for
      infection. Moreover, the high dosages of corticosteroids required with this
      regimen can cause substantial toxicity. Therefore, a number of modifications to
      the regimen have been evaluated in an effort to improve its tolerability and
      efficacy. These include replacing doxorubicin with pegylated liposomal
      doxorubicin and using a reduced frequency of dexamethasone, and, later, the
      addition of thalidomide. The results of an ongoing study demonstrated that this
      latest regimen (including thalidomide) is associated with an improved response
      rate and a higher quality of response compared with previous regimens in patients
      with relapsed/refractory multiple myeloma. This modified regimen is well
      tolerated when prophylactic and supportive measures are incorporated. Although
      additional follow-up is required to determine the effect on survival, this
      modified regimen has significant potential in the management of advanced myeloma.

PMID- 14671228
TI  - Editorial comment--degree of arterial recanalization: an end point for efficacy
      in future intravenous thrombolytic trials.

PMID- 14671229
TI  - Editorial comment--the MOST score: modifying the open-artery "good"-closed-artery
      "bad" approach to thrombolysis prognosis.

PMID- 14671230
TI  - Call TIAs "TIBs".

PMID- 14671231
TI  - Yin and yang of uric acid in patients with stroke.

PMID- 14671232
TI  - Re: External carotid artery territory ischemia impairs outcome in the
      endovascular filament model of middle cerebral artery occlusion in rats.

PMID- 14671234
TI  - Restarting oral anticoagulation after intracranial hemorrhage.

PMID- 14671235
TI  - Dysexecutive syndrome after mild cerebral ischemia? Mice learn normally but have
      deficits in strategy switching.
AB  - BACKGROUND AND PURPOSE: We determined long-term functional outcome in a well
      characterized mouse model of mild focal cerebral ischemia. METHODS: We subjected
      129/SV mice to sham operation or 30 minutes of left middle cerebral artery
      occlusion (MCAo) followed by reperfusion (89% survival rate). Six weeks later,
      animals were tested for neurological deficits, motor coordination on an
      accelerating Rota-rod apparatus, and spatial navigation in a water maze task.
      Brain lesion size was determined on NeuN-immunostained coronal brain sections by
      computer-assisted volumetry. RESULTS: Mice had mild but distinct neurological
      deficits and no deficits in Rota-rod coordination or swimming speed 6 weeks after
      MCAo. Moreover, mice had normal spatial learning abilities in the place task.
      However, stroke mice had deficits in the probe trial and visible platform task,
      which correlated with striatal lesion size determined on NeuN-immunostained
      sections. CONCLUSIONS: After mild ischemia, mice recover with mild neurological
      deficits and normal motor coordination. Stroke mice have no obvious deficits in
      spatial learning in the Morris water maze but display distinct deficits related
      to strategy switching and relearning.

PMID- 14671236
TI  - Poststroke hyperglycemia: natural history and immediate management.
AB  - BACKGROUND AND PURPOSE: Poststroke hyperglycemia (PSH) is a frequent finding for
      which there is currently no evidence to justify routine treatment. The United
      Kingdom Glucose Insulin in Stroke Trial (GIST-UK) is the only trial of glucose
      modulation in acute stroke from which evidence can be derived for the immediate
      management of PSH. Using safety-monitoring data from the trial we aimed to
      describe the immediate recovery of PSH in treated and control patients, thus
      providing evidence for the use of glucose/potassium/insulin (GKI) infusions as a
      means of maintaining euglycemia. METHODS: GIST-UK is a multicenter randomized
      controlled trial of GKI or saline infusions in acute stroke patients presenting
      with mild to moderate hyperglycemia (admission plasma glucose, 6.0 to 17 mmol).
      We analyzed the capillary BM and plasma glucose values in the 2 treatment groups
      to describe the recovery of PSH and the effectiveness of the GIST treatment
      regimen in maintaining euglycemia. RESULTS: The majority of patients have only
      moderate PSH (mean plasma glucose, 8.37+/-SD 2.13). Without specific
      intervention, mean plasma glucose levels decline spontaneously. Treatment with
      the GIST GKI regimen rapidly achieved euglycemia at significantly lower levels
      than with saline hydration alone. Euglycemia was achieved with a median of 2
      changes to the GKI regimen and a low risk of hypoglycemia. CONCLUSIONS: GKI
      infusions as described in the GIST trial are a safe and effective means of
      correcting PSH and maintaining euglycemia in the acute phase of stroke. The
      clinical benefits of routine management of hyperglycemia remain to be determined.

PMID- 14671237
TI  - Clinicotopographical correlation of corticospinal tract stroke: a color-coded
      diffusion tensor imaging study.
AB  - Background- Small capsular strokes are difficult to assess with regard to the
      precise location and the extent of pyramidal tract damage with conventional brain
      imaging. Color-coded diffusion tensor imaging (CDTI) provides a means to
      visualize the course of the corticospinal tract within the white matter. In
      addition to T2-weighted MRI, diffusion-weighted MRI and CDTI were used to analyze
      the topographical patterns of small lacunar corticospinal tract strokes. METHODS:
      We examined 15 patients with pyramidal tract strokes in the subacute phase (days
      3 to 7). Lesions were identified on diffusion-weighted MRI and superimposed on
      CDTI images. The anatomic location and pattern of the lesion were visualized on
      CDTI with regard to the corticospinal tract and subsequently compared with the
      clinical presentation. In addition, infarct areas were evaluated with
      quantitative parameters: mean diffusivity and lattice anisotropy index of lesions
      were determined. RESULTS: We identified 5 different patterns of corticospinal
      tract stroke falling into 2 clinical subgroups: (1) those with marked deficits
      and minor improvement (6/15) and (2) those with good recovery (9/15). Group 1 had
      long lesions centered in the pyramidal tract, involving the basal ganglia
      (anterior choroidal artery); group 2 lesions were very small and/or located
      anteriorly and medially (periventricular anterior choroidal artery territory;
      thalamogeniculate, tuberothalamic, and lateral striate branches). Lesions showed
      a significant increase of mean diffusivity and decrease of lattice anisotropy.
      CONCLUSIONS: CDTI allows in vivo differentiation of distinct subcortical stroke
      subtypes. Improved anatomic definition of lesion localization using CDTI may help
      in better establishing the prognosis for patients after subcortical stroke.

PMID- 14671238
TI  - Randomized controlled trial of an early discharge rehabilitation service: the
      Belfast Community Stroke Trial.
AB  - BACKGROUND AND PURPOSE: To compare a community-based multidisciplinary stroke
      team (CST) approach with hospital-based rehabilitation in terms of hospital stay,
      functioning, quality of life, and service use and costs. METHODS: Stroke patients
      who met pre-agreed criteria were allocated randomly to the CST service (n=59) or
      to usual inpatient rehabilitation and follow-up care (n=54). Assessments were
      completed at randomization and 12 months later. Caregiver strain and satisfaction
      (n=55) were also assessed. Cost data were collected for a subsample of 38
      patients. RESULTS: Almost 80% of surviving patients (n=691) were discharged home
      and a small number (n=55) were readmitted. Approximately 17% (113/649) were
      randomized. There were no statistically significant differences in hospital
      duration, costs, or outcome measures at baseline and 12 months except for higher
      satisfaction reported by CST patients. Overall, both groups recorded improvement
      in most domains over time. Carers reported a high level of satisfaction although
      the level of strain among carers is cause for concern. The community group (n=18)
      cost less than the hospital group (n=20). CONCLUSIONS: A mixed model of hospital
      based and community-based rehabilitation services is likely to lead to increased
      patient choice and satisfaction and a potential reduction in bed pressures for
      less severe stroke patients.

PMID- 14671239
TI  - Na+/H+ exchanger inhibitor, SM-20220, is protective against excitotoxicity in
      cultured cortical neurons.
AB  - BACKGROUND AND PURPOSE: Recently, it has been reported that Na+/H+ exchanger
      (NHE) inhibitors demonstrated protective effects on ischemia/reperfusion brain
      injury in animal models. However, the mechanisms by which the neurons were
      protected against ischemic insult remain unclear. To reveal the cellular
      mechanism of the NHE inhibitor on the neuronal death, we examined the effects of
      a selective NHE inhibitor, SM-20220 (N-[aminoiminomethyl]-1-methyl-1H-indole-2
      carboxamide methanesulfonate), on glutamate-induced neuronal death in rat
      cortical culture. METHODS: Cortical neurons were prepared from 1-day old rats,
      and cultured on the glass-based dishes. Glutamate-induced neuronal death was
      assessed by staining the cells with propidium iodide. Morphological changes in
      the neurons were observed with a video-enhanced contrast-differential
      interference contrast microscope. The intracellular calcium concentration
      ([Ca2+]i) and the intracellular pH (pHi) were measured by fluorescence imaging
      with a confocal laser microscope using fluo-3/acetoxymethylester (AM) and 2', 7'
      bis-2-carboxy-ethyl-5(6)-carboxyfluorescein (BCECF)/AM as a fluorescent dye,
      respectively. RESULTS: SM-20220 (0.3 to 30 nmol/L) dose-dependently attenuated
      glutamate (300 micromol/L)-induced neuronal death over a period of 6 hours, and
      inhibited the acute cellular swelling following glutamate (500 micromol/L)
      exposure. Dual peaks of [Ca2+]i rise were observed at 5 and 12 minutes after
      glutamate (500 micromol/L) exposure, followed by a persistent rise. SM-20220
      suppressed the persistent [Ca2+]i increase. SM-20220 inhibited intracellular
      acidification following glutamate (500 micromol/L) exposure. All of the events
      induced by glutamate were also inhibited by the N-methyl-d-aspartate receptor
      antagonist, MK-801, indicating the death process was excitotoxicity. CONCLUSIONS:
      NHE inhibitor is neuroprotective through inhibition of both persistent [Ca2+]i
      increase and acidification in excitotoxicity.

PMID- 14671240
TI  - A common polymorphism of the protein Z gene is associated with protein Z plasma
      levels and with risk of cerebral ischemia in the young.
AB  - BACKGROUND AND PURPOSE: The vitamin K-dependent protein Z (PZ) has been shown to
      possess anticoagulant as well as procoagulant properties. Plasma levels of PZ
      show a broad interindividual variation, but it is unknown to which extent this
      variation is under genetic control. Recent clinical studies revealed
      contradictory results on the association of PZ plasma levels and the risk of
      ischemic stroke. METHODS: We performed a case-control study including 200
      patients with cerebral ischemia aged < or =50 years and 199 control subjects from
      the same South German region. We investigated a possible association of 2 common
      single nucleotide mutations in the PZ gene with the risk of cerebral ischemia.
      Furthermore, enzyme-linked immunosorbent assay measurements were done in control
      subjects without vascular disease to detect a potential association of different
      genotypes with PZ plasma (antigen) levels. RESULTS: In patients, the frequency of
      the A allele of the intron F polymorphism G79A was significantly lower than in
      controls (15.7% versus 24.4%; odds ratio, 0.58; 95% CI, 0.39 to 0.86; P=0.007;
      adjusted for age, sex, and conventional risk factors). The G allele of the
      promoter polymorphism A-13G tended to be less common in patients (4.2% versus
      7.0%; adjusted odds ratio, 0.56; 95% CI, 0.28 to 1.13; P=0.105). In 42 control
      subjects, the A allele of the intron F polymorphism was associated with lower PZ
      antigen levels (P=0.0032; Spearman correlation coefficient rs=-0.48).
      CONCLUSIONS: The A allele of an intron F polymorphism of the PZ gene appears to
      be a novel protective genetic marker for the risk of cerebral ischemia in young
      adults. In the context of juvenile stroke, high PZ plasma levels may represent a
      prothrombotic condition.

PMID- 14671241
TI  - Direction of flow in posterior communicating artery on magnetic resonance
      angiography in patients with occipital lobe infarcts.
AB  - BACKGROUND AND PURPOSE: In some people the blood supply to the posterior cerebral
      artery occurs partly or even exclusively via the carotid system. This anatomic
      configuration may influence the risk of occipital lobe infarction. We studied the
      presence and direction of flow in the posterior communicating artery (PCoA) in
      patients with an occipital lobe infarct and in healthy controls. METHODS: Forty
      seven patients with an occipital lobe infarct were studied by MR angiography, as
      well as 50 young healthy controls. Special attention was paid to the presence of
      a PCoA and, if present, to the direction of flow. RESULTS: Significantly fewer
      patients than controls had an exclusive blood supply to the posterior cerebral
      artery via the carotid system, in both the affected (4% versus 17%; 95% CI of
      difference, 4% to 22%) and unaffected hemispheres (5% versus 17%; 95% CI of
      difference, 3% to 22%). Patients also less often had a patent PCoA with
      anteroposterior flow than controls (affected hemisphere, 8% versus 22%;
      unaffected hemisphere, 12% versus 22%; 95% CI of differences, 3% to 25% and -2%
      to 23%, respectively). With analysis at the level of individuals, significantly
      more patients showed no anteroposterior flow through the PCoA in either
      hemisphere than controls (79% versus 42%; 95% CI of difference, 19% to 55%).
      CONCLUSIONS: Supply of the posterior cerebral artery by the carotid system occurs
      less often in patients with an occipital lobe infarct than in healthy controls.
      The same was true for the unaffected hemisphere of patients, which suggests that
      the anatomic difference represents a causal factor (fewer collateral pathways
      after occlusion of the posterior cerebral artery or its branches) rather than a
      consequence (redistribution of blood flow after occipital infarction).

PMID- 14671242
TI  - Antiplatelet effect of aspirin in patients with cerebrovascular disease.
AB  - BACKGROUND AND PURPOSE: Aspirin is used commonly to prevent ischemic strokes and
      other vascular events. Although aspirin is considered safe and effective, it has
      limited efficacy with a relative risk reduction of 20% to 25% for ischemic
      stroke. We sought to determine if aspirin as currently used is having its desired
      antiplatelet effects. METHODS: We ascertained patients with cerebrovascular
      disease who were taking only aspirin as an antiplatelet agent. Platelet function
      was evaluated using a platelet function analyzer (PFA-100). PFA test results were
      correlated with aspirin dose, formulation, and basic demographic factors.
      RESULTS: We ascertained 129 patients, of whom 32% were taking an enteric-coated
      aspirin preparation and 32% were taking low-dose (< or =162 mg/d) aspirin. For
      the entire cohort, 37% of patients had normal PFA-100 results, indicating normal
      platelet function. For the patients taking low-dose aspirin, 56% had normal PFAs
      compared with 28% of those taking > or =325 mg/d of aspirin, while 65% of
      patients taking enteric-coated aspirin had normal PFAs compared with 25% taking
      an uncoated preparation (P<0.01 for both comparisons). Similar results were
      obtained if PFA results were analyzed using mean closure times (low-dose aspirin,
      183 sec; high-dose aspirin, 233 sec; enteric-coated, 173 sec; uncoated, 235 sec;
      P<0.01 for comparisons). Older patients and women were less likely to have a
      therapeutic response to aspirin, independent of aspirin dose or formulation.
      CONCLUSIONS: A significant proportion of patients taking low-dose aspirin or
      enteric-coated aspirin have normal platelet function as measured by the PFA-100
      test. If these results correlate with clinical events, they have broad
      implications in determining how aspirin is used and monitored.

PMID- 14671243
TI  - Folate, vitamin B6, and B12 intakes in relation to risk of stroke among men.
AB  - BACKGROUND AND PURPOSE: Folate, vitamin B6, and B12 deficiency are related to
      elevated blood homocysteine level. However, the effects of intakes of these
      vitamins on risk of stroke are still uncertain. This study examines intakes of
      folate, vitamin B6, and B12 in relation to risk of ischemic and hemorrhagic
      stroke. METHODS: We enrolled 43 732 men, aged 40 to 75 years, who were free of
      cardiovascular diseases and diabetes at baseline. Participants were followed from
      1986 to 2000. Dietary information was assessed every 4 years using a detailed and
      validated semiquantitative food frequency questionnaire. The main outcome
      measures were incident ischemic and hemorrhagic strokes. RESULTS: A total of 725
      incident strokes, including 455 ischemic, 125 hemorrhagic, and 145 unknown types
      of stroke, were documented during the 14-year follow-up. After adjustment for
      major lifestyle and dietary factors, intake of folate was associated with a
      significantly lower risk of ischemic but not hemorrhagic stroke. The multivariate
      relative risk of ischemic stroke was 0.71 (95% CI, 0.52 to 0.96; P for
      trend=0.05) for men in the highest quintile of intake compared with those who in
      the lowest quintile. Intake of vitamin B12, but not B6, was also inversely
      associated with risk of ischemic stroke. CONCLUSIONS: Our findings suggest that
      increased folate intake is associated with decreased risk of ischemic stroke in
      men.

PMID- 14671244
TI  - Detection of reversed basilar flow with power-motion Doppler after acute
      occlusion predicts favorable outcome.
AB  - BACKGROUND AND PURPOSE: Power-motion transcranial Doppler PMD-TCD is a new method
      for simultaneous display of flow at multiple depths. We aimed to determine
      clinical significance of PMD-TCD demonstration of reversed basilar flow in
      patients with basilar artery (BA) occlusion. METHODS: We prospectively evaluated
      patients with acute vertebrobasilar ischemia using PMD-TCD. Using a predefined
      set of TCD depth criteria and specific flow findings, occlusion was localized to
      the proximal, middle, or distal BA stem. The National Institutes of Health Stroke
      Scale was used to measure stroke severity and the modified Rankin Scale (mRS) to
      assess outcome at 3 months. RESULTS: BA occlusion was diagnosed in 16 patients (3
      women, mean age 65, median NIHSS 8, mean time from symptoms onset 8.5 hours). PMD
      TCD diagnosis of BA occlusion was confirmed in 11 of 12 patients who underwent
      invasive angiography. Reversed BA flow on PMD-TCD was identified in 8 patients
      (50%). Angiography confirmed flow from carotid system in 6 of these 8 patients
      (kappa=0.87). Patients with reversed BA flow showed lower NIHSS scores on
      admission (median 4 versus 15.5, P=0.009), on discharge (2 versus 21.5, P=0.03)
      and did not experience neurological deterioration during hospital stay (n=0
      versus 4, P=0.05). There was a trend toward better outcome at 3 months (mRS 1
      versus 4, P=0.07). CONCLUSIONS: Detection of reversed flow in the distal BA with
      PMD-TCD is associated with lower stroke severity and better outcome after acute
      basilar artery occlusion.

PMID- 14671245
TI  - Improving the predictive accuracy of recanalization on stroke outcome in patients
      treated with tissue plasminogen activator.
AB  - BACKGROUND AND PURPOSE: Although early recanalization is a powerful predictor of
      stroke outcome after thrombolysis, some stroke patients remain disabled despite
      tissue plasminogen activator (tPA)-induced recanalization. Therefore, we sought
      to investigate whether the predictive accuracy of early recanalization on stroke
      outcome is improved when combined with clinical and radiological information.
      METHODS: We evaluated 177 patients with nonlacunar strokes in the middle cerebral
      artery (MCA) treated with intravenous tPA who were followed up during 3 months.
      Transcranial Doppler monitoring of recanalization was conducted during the first
      hours after tPA administration. The relative contribution of clinical,
      transcranial Doppler, and radiological information on stroke outcome was
      evaluated. We used logistic regression to derive a predictive model for good
      outcome (modified Rankin Scale score < or =2) after thrombolysis. RESULTS: Median
      National Institutes of Health Stroke Scale (NIHSS) score before tPA was 16. At 3
      months, 87 patients (49.2%) became functionally independent (modified Rankin
      Scale score < or =2). In a logistic regression model, degree of recanalization
      within 300 minutes (P<0.001), proximal MCA occlusion (P<0.001), baseline NIHSS
      score (P=0.0013), systolic blood pressure (P=0.0116), and early ischemic changes
      on CT (P=0.0253) independently predicted outcome at 3 months. A 5-item score was
      developed on the basis of the factors significantly associated with stroke
      outcome in the logistic regression (total score range, 0 to 7). The likelihood of
      good outcome at 3 months was 0.82 (95% CI, 0.72 to 0.92) in patients who scored 0
      to 2, 0.51 (95% CI, 0.36 to 0.66) in those who scored 3 to 4, and 0.15 (95% CI,
      0.05 to 0.25) in those who scored 5 to 7 points. CONCLUSIONS: The combination of
      clinical, radiological, and hemodynamic information predicts with a high accuracy
      long-term stroke outcome during or shortly after intravenous tPA administration.

PMID- 14671246
TI  - Effect of incomplete (spontaneous and postthrombolytic) recanalization after
      middle cerebral artery occlusion: a magnetic resonance imaging study.
AB  - BACKGROUND AND PURPOSE: Early reperfusion is one of the best predictors of good
      outcome after acute middle cerebral artery (MCA) occlusion. The purpose of this
      study was to analyze the frequency and relevance of incomplete recanalization for
      tissue and clinical outcome. METHODS: From a larger acute stroke database
      (Kompetenznetzwerk Schlaganfall B5), all patients (n=82) with MCA main stem
      occlusion (excluding carotid T-occlusions) were selected. These patients had
      received a multiparametric stroke MRI protocol including diffusion- and perfusion
      weighted imaging (DWI, PWI) and MR angiography (MRA) within 6 hours after symptom
      onset, at day 1 and after 1 week. Recanalization status was determined with MRA
      on day 1 (according to Thrombolysis In Myocardial Infarction flow grades) and
      used to group patients into those with persistent occlusion (0) or minimal (1),
      partial (2), or complete (3) recanalization. RESULTS: Incomplete recanalization
      according to MRI criteria was found in 39 patients (grade 1: n=20; grade 2:
      n=19), complete recanalization in 10, and persistent occlusion in 33. There was
      no statistically significant difference in any of the clinical (National
      Institutes of Health Stroke Scale score) or MRI baseline parameters (DWI lesion,
      PWI deficit, mismatch volume, mismatch ratio). However, lesion growth was smaller
      in patients with recanalization (even in patients with only minimal
      recanalization) and outcome was related to the degree of recanalization (mean
      modified Rankin score at 90 days: 3.36, 2.70, 1.79, and 1.44 for the groups with
      no, minimal, partial, and complete recanalization, respectively). Both incomplete
      and complete recanalization was more frequent in patients receiving thrombolysis.
      CONCLUSIONS: Incomplete recanalization on day 1 is a frequent MR finding after
      MCA main stem occlusion, indicating a more favorable clinical course than
      persistent occlusion. MR indicators of early recanalization could be useful
      surrogates of efficacy in thrombolytic trials.

PMID- 14671247
TI  - Effects of a perindopril-based blood pressure-lowering regimen on the risk of
      recurrent stroke according to stroke subtype and medical history: the PROGRESS
      Trial.
AB  - BACKGROUND AND PURPOSE: The Perindopril Protection Against Recurrent Stroke Study
      (PROGRESS) showed that blood pressure lowering reduced stroke risk in patients
      with a history of cerebrovascular events. Here, we report the consistency of
      treatment effects across different stroke subtypes and among major clinical
      subgroups. METHODS: PROGRESS was a randomized, double-blind trial among 6105
      people with a prior history of cerebrovascular events. Participants were assigned
      to active treatment (perindopril for all participants and indapamide for those
      with neither an indication for nor a contraindication to a diuretic) or matching
      placebo(s). RESULTS: During a mean of 3.9 years of follow-up, active treatment
      reduced the absolute rates of ischemic stroke from 10% to 8% (relative risk
      reduction [RRR], 24%; 95% confidence interval [CI], 10 to 35) and the absolute
      rates of intracerebral hemorrhage from 2% to 1% (RRR, 50%; 95% CI, 26 to 67). The
      relative risk of any stroke during follow-up was reduced by 26% (95% CI, 12 to
      38) among patients whose baseline cerebrovascular event was an ischemic stroke
      and by 49% (95% CI, 18 to 68) among those whose baseline event was an
      intracerebral hemorrhage. There was no evidence that treatment effects were
      modified by other drug therapies (antiplatelet or other antihypertensive agents),
      residual neurological signs, atrial fibrillation, or the time since the last
      cerebrovascular event. CONCLUSIONS: Beneficial effects of a perindopril-based
      treatment regimen were observed for all stroke types and all major clinical
      subgroups studied. These data suggest that effective blood pressure-lowering
      therapy should be routinely considered for all patients with a history of
      cerebrovascular events.

PMID- 14671248
TI  - William M. Feinberg Lecture: stroke therapy in the year 2025: burden,
      breakthroughs, and barriers to progress.
AB  - BACKGROUND: More than 700 000 strokes occurred in the United States during 2002,
      of which approximately 500 000 are first-ever strokes and 200 000 recurrent
      strokes. If we would decrease the enormous burden of stroke throughout the world,
      we first need to know the barriers that we have to overcome. These are quite
      similar to the barriers that we have tried to surmount during the last 25 years.
      STOKE PREVENTION: We have developed many successful primary and secondary
      therapies to prevent stroke over the past 25 years and have begun to understand
      some of the genetic risk factors underlying stroke. Yet, the incidence rate of
      stroke in Rochester, Minn, remained unchanged from 1975 to the mid-1990s, and
      mortality rates for Ohio have changed little for men, women, blacks, and whites
      over the past decade. The primary reason that we have made little progress in
      decreasing the burden of stroke is that we have made little progress in modifying
      the primary risk factors for stroke in the population. Other barriers of improved
      stroke prevention in the future include costs of therapy and aging of blood
      vessels and brain, which is the most important risk factor for stroke. ACUTE
      STROKE: Breakthroughs in acute stroke treatment are likely to follow the steps of
      cardiology with the primary focus for ischemic stroke on the restoration of
      oxygenated blood flow to ischemic brain as quickly as possible. To improve acute
      stroke therapy in the year 2025, we need to have more focused messages sent to
      the lay public about stroke warning signs, better and safer methods to open
      arteries quickly, truly effective neuroprotection in the setting of reperfusion,
      regional organization for acute stroke therapy, and large randomized trials to
      find clinically important but smaller benefits. A scientifically proven treatment
      for treatment of acute intracerebral hemorrhage is another major goal. RECOVERY
      AFTER STROKE: Brain recovery after stroke is the area of scientific discovery
      with the largest potential for advances far into the next century. Obstacles that
      block effective therapies in the recovery from stroke include the extent of
      initial injury from stroke, the brain plasticity of a given patient, and, most
      importantly, understanding the "neural code"-how the brain is organized and how
      cells communicate with one another.

PMID- 14671249
TI  - Influence of arterial input function on hypoperfusion volumes measured with
      perfusion-weighted imaging.
AB  - BACKGROUND AND PURPOSE: The arterial input function (AIF) is critical in
      determining hemodynamic parameters quantitatively with bolus-tracking MRI. We
      studied the effect of varying the location of measurement of AIF on the volume of
      hypoperfusion. We compared the volumes of hypoperfusion obtained with different
      AIFs with the final ischemic lesion volume. METHODS: We included 13 patients with
      acute cerebral ischemia in the anterior circulation who underwent diffusion-
      (DWI) and perfusion (PWI)-weighted imaging within 8 hours after symptom onset and
      exhibited DWI lesion expansion between baseline and follow-up. AIF was measured
      at 4 locations: near both middle cerebral arteries (MCAs), in MCA branches
      adjacent to the largest DWI abnormality, and at the same level on the opposite
      hemisphere. Hypoperfusion lesion volumes were compared with the DWI volume at
      follow-up. RESULTS: Large variations in PWI lesion size were found with different
      AIF locations. The largest PWI lesions were found when AIF was measured at the
      contralateral MCA. Smaller PWI lesions were found when AIF was measured in the
      other locations. There was no significant difference between PWI lesion area at
      baseline and follow-up DWI lesion when AIF was measured at the contralateral MCA.
      The other PWI lesions significantly underestimated follow-up DWI lesion size.
      CONCLUSIONS: AIF is an important determinant of the size of hypoperfusion lesions
      measured with PWI. PWI lesion volumes determined with AIF from the contralateral
      MCA are associated with follow-up lesion volume.

PMID- 14671250
TI  - Novel diagnostic test for acute stroke.
AB  - BACKGROUND AND PURPOSE: The absence of a widely available and sensitive
      diagnostic test for acute cerebral ischemia remains a significant limitation in
      the diagnosis and management of stroke. The objective of this study was to
      examine the feasibility of developing a diagnostic panel of blood-borne
      biochemical markers of cerebral ischemia. METHODS: Serial blood samples were
      obtained from patients (n=65 with suspected ischemic stroke, n=157 control
      subjects) presenting to an academic medical center emergency department. We
      analyzed 26 blood-borne markers believed to play a role in the ischemic cascade
      and created a 3-variable logistic regression model to predict the clinical
      diagnosis of stroke, defined as persistent neurological symptoms of cerebral
      ischemia lasting >24 hours. RESULTS: Of the 26 blood-borne markers analyzed,
      univariate logistic analysis revealed that 4 were highly correlated with stroke
      (P<0.001): a marker of glial activation (S100beta), 2 markers of inflammation
      (matrix metalloproteinase-9 and vascular cell adhesion molecule), and 1 marker of
      thrombosis (von Willebrand factor). When the outcome level was set to a cutoff of
      P=0.1, our logistic model provided a sensitivity and specificity of 90% for
      predicting stroke. CONCLUSIONS: A panel of blood-borne biochemical markers may be
      helpful in identifying patients with acute cerebral ischemia who could benefit
      from urgent care. Such a test may also be helpful in identifying stroke patients
      in the prehospital setting so that they could be fast-tracked to an institution
      equipped to care for patients with acute stroke.

PMID- 14671251
TI  - Decreased levels of plasma vitamin C and increased concentrations of inflammatory
      and oxidative stress markers after stroke.
AB  - BACKGROUND AND PURPOSE: Inflammatory response is a critical component of the
      complex pathophysiological response to stroke. Vitamin C has been shown to have
      important roles in cell performance and vascular function. In this study, we
      compared the nutritional status and levels of inflammatory markers between stroke
      cases and controls and assessed which antioxidant was associated with levels of
      inflammatory markers and oxidative stress among cases and controls. METHODS: We
      evaluated the nutritional status and measured plasma levels of vitamins C and E,
      uric acid, serum levels of C-reactive protein (CRP), the cytokines tumor necrosis
      factor-alpha and interleukin-1beta, intercellular adhesion molecule-1 (ICAM-1)
      and chemokine monocyte chemoattractant protein-1 (MCP-1), prostaglandins PGE2 and
      PGI2, and 8-isoprostanes (8-epiPGF2alpha) for 15 patients with ischemic stroke
      within 2 to 5 days after stroke onset and for 24 control subjects. RESULTS:
      Stroke patients had significantly lower plasma levels of vitamin C than did
      controls. Among stroke patients, CRP was significantly elevated, as were the ICAM
      1, MCP-1, and 8-epiPGF2alpha, but the prostaglandins PGE2 and PGI2 were
      significantly reduced. Interestingly, vitamin C concentration was significantly
      inversely correlated with the levels of CRP and 8-epiPGF2alpha among stroke
      patients, and 8-epiPGF2alpha was significantly associated with the levels of CRP.
      Uric acid was also elevated among stroke patients. CONCLUSIONS: Lower vitamin C
      concentration, higher serum levels of inflammatory (CRP, ICAM-1, MCP-1) and
      oxidative stress (8-epiPGF2alpha) markers, and lower PGI2 and PGE2 concentrations
      among stroke patients indicate the presence of an inflammatory response
      associated with stroke.

PMID- 14671252
TI  - Sustainability and the commons.

PMID- 14671253
TI  - European Union. E.U. stem cell debate ends in a draw.

PMID- 14671254
TI  - Biomedical research. Defunded VA grants restored; Wray returns to Texas.

PMID- 14671255
TI  - Human space flight. Bush plan for NASA: watch this space.

PMID- 14671256
TI  - Embryonic stem cells. Scientists make sperm in a dish.

PMID- 14671257
TI  - Evolution. Genome comparisons hold clues to human evolution.

PMID- 14671258
TI  - Evolution. Chimp genome draft online.

PMID- 14671260
TI  - Ocean drilling. Arctic is first call for new global program.

PMID- 14671259
TI  - Geophysics. Faults may gang up on Los Angeles.

PMID- 14671261
TI  - Intellectual property. Patent sprawl: from genes to gene interpretation.

PMID- 14671262
TI  - Forest policy. Critics say new law is a bit thin on science.

PMID- 14671263
TI  - Academic leaders. Vest steps down as MIT president.

PMID- 14671265
TI  - Graduate education. Who's No. 1? Academy hopes new rankings will say more.

PMID- 14671264
TI  - Imaging. Animal models: live and in color.

PMID- 14671266
TI  - Careers. Age bar forces Europe's senior researchers to head west.

PMID- 14671267
TI  - Nutrition. The vitamin D deficit.

PMID- 14671268
TI  - Geological Society of America meeting. Pacific migration arrested by meltdown's
      high waters.

PMID- 14671269
TI  - Geological Society of America meeting. Wanderlust in the western margin.

PMID- 14671270
TI  - The human cost of the SSC.

PMID- 14671271
TI  - The lesson of the SSC.

PMID- 14671272
TI  - Decommissioning Russia's nuclear subs.

PMID- 14671273
TI  - Building a space weather aerie in Armenia.

PMID- 14671275
TI  - Comment on "Tumor response to radiotherapy regulated by endothelial cell
      apoptosis" (II).

PMID- 14671276
TI  - Life scientists and the dual use dilemma.

PMID- 14671277
TI  - Comment on "Tumor response to radiotherapy regulated by endothelial cell
      apoptosis" (I).

PMID- 14671278
TI  - Europe's fight for the tree of life.

PMID- 14671279
TI  - Public health. Understanding threats to scientific openness.

PMID- 14671280
TI  - Paleontology. Marsupial origins.

PMID- 14671281
TI  - Microbiology. Chemical warfare and mycobacterial defense.

PMID- 14671282
TI  - Astronomy. The hunt for dark matter in galaxies.

PMID- 14671283
TI  - Neuroscience. The ups and downs of Wnt signaling.

PMID- 14671284
TI  - Chemistry. Polymers get organized.

PMID- 14671286
TI  - The struggle to govern the commons.
AB  - Human institutions--ways of organizing activities--affect the resilience of the
      environment. Locally evolved institutional arrangements governed by stable
      communities and buffered from outside forces have sustained resources
      successfully for centuries, although they often fail when rapid change occurs.
      Ideal conditions for governance are increasingly rare. Critical problems, such as
      transboundary pollution, tropical deforestation, and climate change, are at
      larger scales and involve nonlocal influences. Promising strategies for
      addressing these problems include dialogue among interested parties, officials,
      and scientists; complex, redundant, and layered institutions; a mix of
      institutional types; and designs that facilitate experimentation, learning, and
      change.

PMID- 14671287
TI  - Social capital and the collective management of resources.
AB  - The proposition that natural resources need protection from the destructive
      actions of people is widely accepted. Yet communities have shown in the past and
      increasingly today that they can collaborate for long-term resource management.
      The term social capital captures the idea that social bonds and norms are
      critical for sustainability. Where social capital is high in formalized groups,
      people have the confidence to invest in collective activities, knowing that
      others will do so too. Some 0.4 to 0.5 million groups have been established since
      the early 1990s for watershed, forest, irrigation, pest, wildlife, fishery, and
      microfinance management. These offer a route to sustainable management and
      governance of common resources.

PMID- 14671288
TI  - Managing tragedies: understanding conflict over common pool resources.
AB  - Conflicts over the management of common pool resources are not simply material.
      They also depend on the perceptions of the protagonists. Policy to improve
      management often assumes that problems are self-evident, but in fact careful and
      transparent consideration of the ways different stakeholders understand
      management problems is essential to effective dialogue.

PMID- 14671289
TI  - Global food security: challenges and policies.
AB  - Global food security will remain a worldwide concern for the next 50 years and
      beyond. Recently, crop yield has fallen in many areas because of declining
      investments in research and infrastructure, as well as increasing water scarcity.
      Climate change and HIV/AIDS are also crucial factors affecting food security in
      many regions. Although agroecological approaches offer some promise for improving
      yields, food security in developing countries could be substantially improved by
      increased investment and policy reforms.

PMID- 14671290
TI  - New visions for addressing sustainability.
AB  - Attaining sustainability will require concerted interactive efforts among
      disciplines, many of which have not yet recognized, and internalized, the
      relevance of environmental issues to their main intellectual discourse. The
      inability of key scientific disciplines to engage interactively is an obstacle to
      the actual attainment of sustainability. For example, in the list of Millennium
      Development Goals from the United Nations World Summit on Sustainable
      Development, Johannesburg, 2002, the seventh of the eight goals, to "ensure
      environmental sustainability," is presented separately from the parallel goals of
      reducing fertility and poverty, improving gains in equity, improving material
      conditions, and enhancing population health. A more integrated and consilient
      approach to sustainability is urgently needed.

PMID- 14671291
TI  - The burden of chronic disease.
AB  - The shift from acute infectious and deficiency diseases to chronic
      noncommunicable diseases is not a simple transition but a complex and dynamic
      epidemiological process, with some diseases disappearing and others appearing or
      reemerging. The unabated pandemic of childhood and adulthood obesity and
      concomitant comorbidities are affecting both rich and poor nations, while
      infectious diseases remain an important public health problem, particularly in
      developing countries. More attention should be given to the high burden of
      disease associated with soil-transmitted helminths and schistosomiasis, which
      until recently was not considered a priority even though regular drug treatment
      is obtainable at relatively little cost. In developing countries, the pressing
      requirement is to provide an accessible and good quality health-care system,
      whereas industrialized countries have a major need for greater public health
      education and the promotion of healthy life-styles.

PMID- 14671293
TI  - Climate change: the political situation.

PMID- 14671292
TI  - The challenge of long-term climate change.
AB  - Climate policy needs to address the multidecadal to centennial time scale of
      climate change. Although the realization of short-term targets is an important
      first step, to be effective climate policies need to be conceived as long-term
      programs that will achieve a gradual transition to an essentially emission-free
      economy on the time scale of a century. This requires a considerably broader
      spectrum of policy measures than the primarily market-based instruments invoked
      for shorter term mitigation policies. A successful climate policy must consist of
      a dual approach focusing on both short-term targets and long-term goals.

PMID- 14671294
TI  - Tales from a troubled marriage: science and law in environmental policy.
AB  - Early environmental policy depended on science, with mixed results. Newer
      approaches continue to rely on science to identify problems and solve them, but
      use other mechanisms to set standards and legal obligations. Given the important
      role that science continues to play, however, several cautionary tales are in
      order concerning "scientific management," "good science," the lure of money, and
      the tension between objectivity and involvement in important issues of our time.

PMID- 14671295
TI  - An Early Cretaceous tribosphenic mammal and metatherian evolution.
AB  - Derived features of a new boreosphenidan mammal from the Lower Cretaceous Yixian
      Formation of China suggest that it has a closer relationship to metatherians
      (including extant marsupials) than to eutherians (including extant placentals).
      This fossil dates to 125 million years ago and extends the record of marsupial
      relatives with skeletal remains by 50 million years. It also has many foot
      structures known only from climbing and tree-living extant mammals, suggesting
      that early crown therians exploited diverse niches. New data from this fossil
      support the view that Asia was likely the center for the diversification of the
      earliest metatherians and eutherians during the Early Cretaceous.

PMID- 14671296
TI  - Subkelvin cooling NO molecules via "billiard-like" collisions with argon.
AB  - We report the cooling of nitric oxide using a single collision between an argon
      atom and a molecule of NO. We have produced significant numbers (108 to 109
      molecules per cubic centimeter per quantum state) of translationally cold NO
      molecules in a specific quantum state with an upper-limit root mean square
      laboratory velocity of 15 plus or minus 1 meters per second, corresponding to a
      406 plus or minus 23 millikelvin upper limit of temperature, in a crossed
      molecular beam apparatus. The technique, which relies on a kinematic collapse of
      the velocity distributions of the molecular beams for the scattering events that
      produce cold molecules, is general and independent of the energy of the colliding
      partner.

PMID- 14671297
TI  - Importance of surface morphology in interstellar H2 formation.
AB  - Detailed laboratory experiments on the formation of HD from atom recombination on
      amorphous solid water films show that this process is extremely efficient in a
      temperature range of 8 to 20 kelvin, temperatures relevant for H2 formation on
      dust grain surfaces in the interstellar medium (ISM). The fate of the 4.5
      electron volt recombination energy is highly dependent on film morphology. These
      results suggest that grain morphology, rather than the detailed chemical nature
      of the grain surface, is most important in determining the energy content of the
      H2 as it is released from the grain into the ISM.

PMID- 14671298
TI  - Fault interactions and large complex earthquakes in the Los Angeles area.
AB  - Faults in complex tectonic environments interact in various ways, including
      triggered rupture of one fault by another, that may increase seismic hazard in
      the surrounding region. We model static and dynamic fault interactions between
      the strike-slip and thrust fault systems in southern California. We find that
      rupture of the Sierra Madre-Cucamonga thrust fault system is unlikely to trigger
      rupture of the San Andreas or San Jacinto strike-slip faults. However, a large
      northern San Jacinto fault earthquake could trigger a cascading rupture of the
      Sierra Madre-Cucamonga system, potentially causing a moment magnitude 7.5 to 7.8
      earthquake on the edge of the Los Angeles metropolitan region.

PMID- 14671299
TI  - Doubly ionized carbon observed in the plasma tail of comet Kudo-Fujikawa.
AB  - Comet C/2002 X5 (Kudo-Fujikawa) was observed near its perihelion of 0.19
      astronomical unit by the Ultraviolet Coronagraph Spectrometer aboard the Solar
      and Heliospheric Observatory spacecraft. Images of the comet reconstructed from
      high-resolution spectra reveal a quasi-spherical cloud of neutral hydrogen and a
      variable tail of C+ and C2+ that disconnects from the comet and subsequently
      regenerates. The high abundance of C2+ and C+, at least 24% relative to water,
      cannot be explained by photodissociation of carbon monoxide and is instead
      attributed to the evaporation and subsequent photoionization of atomic carbon
      from organic refractory compounds present in the cometary dust grains. This
      result serves to strengthen the connection between comets and the material from
      which the Solar System formed.

PMID- 14671300
TI  - Direct observations of North Pacific ventilation: brine rejection in the Okhotsk
      Sea.
AB  - Brine rejection that accompanies ice formation in coastal polynyas is responsible
      for ventilating several globally important water masses in the Arctic and
      Antarctic. However, most previous studies of this process have been indirect,
      based on heat budget analyses or on warm-season water column inventories. Here,
      we present direct measurements of brine rejection and formation of North Pacific
      Intermediate Water in the Okhotsk Sea from moored winter observations. A steady,
      nearly linear salinity increase unambiguously caused by local ice formation was
      observed for more than a month.

PMID- 14671301
TI  - A gene expression map of the Arabidopsis root.
AB  - A global map of gene expression within an organ can identify genes with
      coordinated expression in localized domains, thereby relating gene activity to
      cell fate and tissue specialization. Here, we present localization of expression
      of more than 22,000 genes in the Arabidopsis root. Gene expression was mapped to
      15 different zones of the root that correspond to cell types and tissues at
      progressive developmental stages. Patterns of gene expression traverse
      traditional anatomical boundaries and show cassettes of hormonal response.
      Chromosomal clustering defined some coregulated genes. This expression map
      correlates groups of genes to specific cell fates and should serve to guide
      reverse genetics.

PMID- 14671302
TI  - Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios.
AB  - Even though human and chimpanzee gene sequences are nearly 99% identical,
      sequence comparisons can nevertheless be highly informative in identifying
      biologically important changes that have occurred since our ancestral lineages
      diverged. We analyzed alignments of 7645 chimpanzee gene sequences to their human
      and mouse orthologs. These three-species sequence alignments allowed us to
      identify genes undergoing natural selection along the human and chimp lineage by
      fitting models that include parameters specifying rates of synonymous and
      nonsynonymous nucleotide substitution. This evolutionary approach revealed an
      informative set of genes with significantly different patterns of substitution on
      the human lineage compared with the chimpanzee and mouse lineages. Partitions of
      genes into inferred biological classes identified accelerated evolution in
      several functional classes, including olfaction and nuclear transport. In
      addition to suggesting adaptive physiological differences between chimps and
      humans, human-accelerated genes are significantly more likely to underlie major
      known Mendelian disorders.

PMID- 14671303
TI  - The proteasome of Mycobacterium tuberculosis is required for resistance to nitric
      oxide.
AB  - The production of nitric oxide and other reactive nitrogen intermediates (RNI) by
      macrophages helps to control infection by Mycobacterium tuberculosis (Mtb).
      However, the protection is imperfect and infection persists. To identify genes
      that Mtb requires to resist RNI, we screened 10,100 Mtb transposon mutants for
      hypersusceptibility to acidified nitrite. We found 12 mutants with insertions in
      seven genes representing six pathways, including the repair of DNA (uvrB) and the
      synthesis of a flavin cofactor (fbiC). Five mutants had insertions in proteasome
      associated genes. An Mtb mutant deficient in a presumptive proteasomal adenosine
      triphosphatase was attenuated in mice, and exposure to proteasomal protease
      inhibitors markedly sensitized wild-type Mtb to RNI. Thus, the mycobacterial
      proteasome serves as a defense against oxidative or nitrosative stress.

PMID- 14671304
TI  - Genome of Geobacter sulfurreducens: metal reduction in subsurface environments.
AB  - The complete genome sequence of Geobacter sulfurreducens, a delta
      proteobacterium, reveals unsuspected capabilities, including evidence of aerobic
      metabolism, one-carbon and complex carbon metabolism, motility, and chemotactic
      behavior. These characteristics, coupled with the possession of many two
      component sensors and many c-type cytochromes, reveal an ability to create
      alternative, redundant, electron transport networks and offer insights into the
      process of metal ion reduction in subsurface environments. As well as playing
      roles in the global cycling of metals and carbon, this organism clearly has the
      potential for use in bioremediation of radioactive metals and in the generation
      of electricity.

PMID- 14671305
TI  - Crystal structure of the RC-LH1 core complex from Rhodopseudomonas palustris.
AB  - The crystal structure at 4.8 angstrom resolution of the reaction center-light
      harvesting 1 (RC-LH1) core complex from Rhodopseudomonas palustris shows the
      reaction center surrounded by an oval LH1 complex that consists of 15 pairs of
      transmembrane helical alpha- and beta-apoproteins and their coordinated
      bacteriochlorophylls. Complete closure of the RC by the LH1 is prevented by a
      single transmembrane helix, out of register with the array of inner LH1 alpha
      apoproteins. This break, located next to the binding site in the reaction center
      for the secondary electron acceptor ubiquinone (UQB), may provide a portal
      through which UQB can transfer electrons to cytochrome b/c1.

PMID- 14671306
TI  - Mono- versus polyubiquitination: differential control of p53 fate by Mdm2.
AB  - Although Mdm2-mediated ubiquitination is essential for both degradation and
      nuclear export of p53, the molecular basis for the differential effects of Mdm2
      remains unknown. Here we show that low levels of Mdm2 activity induce
      monoubiquitination and nuclear export of p53, whereas high levels promote p53's
      polyubiquitination and nuclear degradation. A p53-ubiquitin fusion protein that
      mimics monoubiquitinated p53 was found to accumulate in the cytoplasm in an Mdm2
      independent manner, indicating that monoubiquitination is critical for p53
      trafficking. These results clarify the nature of ubiquitination-mediated p53
      regulation and suggest that distinct mechanisms regulate p53 function in
      accordance with the levels of Mdm2 activity.

PMID- 14671307
TI  - Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on
      HIF1alpha.
AB  - Cells exposed to low oxygen concentrations respond by initiating defense
      mechanisms, including the stabilization of hypoxia-inducible factor (HIF) 1alpha,
      a transcription factor that upregulates genes such as those involved in
      glycolysis and angiogenesis. Nitric oxide and other inhibitors of mitochondrial
      respiration prevent the stabilization of HIF1alpha during hypoxia. In studies of
      cultured cells, we show that this effect is a result of an increase in prolyl
      hydroxylase-dependent degradation of HIF1alpha. With the use of Renilla
      luciferase to detect intracellular oxygen concentrations, we also demonstrate
      that, upon inhibition of mitochondrial respiration in hypoxia, oxygen is
      redistributed toward nonrespiratory oxygen-dependent targets such as prolyl
      hydroxylases so that they do not register hypoxia. Thus, the signaling
      consequences of hypoxia may be profoundly modified by nitric oxide.

PMID- 14671308
TI  - A muscleblind knockout model for myotonic dystrophy.
AB  - The neuromuscular disease myotonic dystrophy (DM) is caused by microsatellite
      repeat expansions at two different genomic loci. Mutant DM transcripts are
      retained in the nucleus together with the muscleblind (Mbnl) proteins, and these
      abnormal RNAs somehow interfere with pre-mRNA splicing regulation. Here, we show
      that disruption of the mouse Mbnl1 gene leads to muscle, eye, and RNA splicing
      abnormalities that are characteristic of DM disease. Our results support the
      hypothesis that manifestations of DM can result from sequestration of specific
      RNA binding proteins by a repetitive element expansion in a mutant RNA.

PMID- 14671309
TI  - High-probability uniquantal transmission at excitatory synapses in barrel cortex.
AB  - The number of vesicles released at excitatory synapses and the number of release
      sites per synaptic connection are key determinants of information processing in
      the cortex, yet they remain uncertain. Here we show that the number of functional
      release sites and the number of anatomically identified synaptic contacts are
      equal at connections between spiny stellate and pyramidal cells in rat barrel
      cortex. Moreover, our results indicate that the amount of transmitter released
      per synaptic contact is independent of release probability and the intrinsic
      release probability is high. These properties suggest that connections between
      layer 4 and layer 2/3 are tuned for reliable transmission of spatially
      distributed, timing-based signals.

PMID- 14671310
TI  - Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling.
AB  - Commissural neurons in the mammalian dorsal spinal cord send axons ventrally
      toward the floor plate, where they cross the midline and turn anteriorly toward
      the brain; a gradient of chemoattractant(s) inside the spinal cord controls this
      turning. In rodents, several Wnt proteins stimulate the extension of commissural
      axons after midline crossing (postcrossing). We found that Wnt4 messenger RNA is
      expressed in a decreasing anterior-to-posterior gradient in the floor plate, and
      that a directed source of Wnt4 protein attracted postcrossing commissural axons.
      Commissural axons in mice lacking the Wnt receptor Frizzled3 displayed anterior
      posterior guidance defects after midline crossing. Thus, Wnt-Frizzled signaling
      guides commissural axons along the anterior-posterior axis of the spinal cord.

PMID- 14671311
TI  - An ion balance for ultra-high-precision atomic mass measurements.
AB  - We have developed the analog of a double-pan balance for determining the masses
      of single molecular ions from the ratio of their two cyclotron frequencies. By
      confining two different ions on the same magnetron orbit in a Penning trap, we
      balance out many sources of noise and error (such as fluctuations of the magnetic
      field). To minimize the systematic error associated with the Coulomb interaction
      between the two ions, they are kept about 1 millimeter apart from each other,
      resulting in fractional uncertainty below 1 x 10(-11). Such precision opens the
      door to numerous applications of mass spectrometry, including metrology,
      fundamental physics, and weighing chemical bonds.

PMID- 14671312
TI  - Defining the epithelial stem cell niche in skin.
AB  - Many adult regenerative cells divide infrequently but have high proliferative
      capacity. We developed a strategy to fluorescently label slow-cycling cells in a
      cell type-specific fashion. We used this method to purify the label-retaining
      cells (LRCs) that mark the skin stem cell (SC) niche. We found that these cells
      rarely divide within their niche but change properties abruptly when stimulated
      to exit. We determined their transcriptional profile, which, when compared to
      progeny and other SCs, defines the niche. Many of the >100 messenger RNAs
      preferentially expressed in the niche encode surface receptors and secreted
      proteins, enabling LRCs to signal and respond to their environment.

PMID- 14671313
TI  - Epigenetic dynamics of imprinted X inactivation during early mouse development.
AB  - The initiation of X-chromosome inactivation is thought to be tightly correlated
      with early differentiation events during mouse development. Here, we show that
      although initially active, the paternal X chromosome undergoes imprinted
      inactivation from the cleavage stages, well before cellular differentiation. A
      reversal of the inactive state, with a loss of epigenetic marks such as histone
      modifications and polycomb proteins, subsequently occurs in cells of the inner
      cell mass (ICM), which give rise to the embryo-proper in which random X
      inactivation is known to occur. This reveals the remarkable plasticity of the X
      inactivation process during preimplantation development and underlines the
      importance of the ICM in global reprogramming of epigenetic marks in the early
      embryo.

PMID- 14671314
TI  - Autoubiquitylation of the V(D)J recombinase protein RAG1.
AB  - V(D)J recombination, the rearrangement of gene segments to assemble Ig and T cell
      receptor coding regions, is vital to B and T lymphocyte development. Here, we
      demonstrate that the V(D)J recombinase protein RAG1 undergoes ubiquitylation in
      cells. In vitro, the RING finger domain of RAG1 acts as a ubiquitin ligase that
      mediates its own ubiquitylation at a highly conserved K residue in the RAG1 amino
      terminal region. Ubiquitylation is best supported by a specific ubiquitin
      conjugating enzyme, UbcH3/CDC34, and requires an intact RAG1 RING finger motif.
      Disruption of the RING finger and certain RAG1 N-terminal truncations are
      associated with immunodeficiency in human patients, suggesting that RAG1's
      ubiquitin ligase is required for its biological role in lymphocyte development.

PMID- 14671315
TI  - Reversing cerebellar long-term depression.
AB  - The discovery of a postsynaptically expressed form of cerebellar parallel fiber
      Purkinje cell long-term potentiation (LTP) raises the question whether this is
      the long-sought resetting mechanism for long-term depression (LTD). Extracellular
      monitoring of PC spikes enables stable prolonged recordings of parallel fiber
      Purkinje cell synaptic efficacy. LTD, saturated by repeated induction protocols,
      can be reversed by a single round of postsynaptic LTP or nitric oxide (NO),
      enabling LTD to be reinduced. Conversely, after postsynaptic LTP has been
      saturated, one round of LTD permits fresh postsynaptic LTP. By contrast, after
      saturation of LTD, induction of presynaptic LTP or application of forskolin
      leaves LTD still saturated. Likewise, presynaptic LTP cannot be reversed by LTD.
      Therefore postsynaptic LTP mediated by NO without postsynaptic Ca2+ elevation,
      unlike presynaptic LTP mediated by cAMP, is a true counterbalance to LTD mediated
      by coincidence of NO plus postsynaptic Ca2+

PMID- 14671316
TI  - Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway
      involving p130 and p107.
AB  - In addition to causing regression of the Mullerian duct in the male embryo,
      Mullerian Inhibiting Substance (MIS) inhibits the growth of epithelial ovarian
      cancer cells, which are known to be of Mullerian origin. Because the uterine
      cervix is derived from the same Mullerian duct precursor as the epithelium of the
      ovary, we tested the hypothesis that cervical cancer cells might also respond to
      MIS. A number of cervical cancer cell lines express the MIS type II receptor, and
      MIS inhibits the growth of both human papilloma virus-transformed and non-human
      papilloma virus-transformed cervical cell lines, with a more dramatic effect seen
      in the latter. As in the ovarian cancer cell line OVCAR8, suppression of growth
      of the C33A cervical cancer cell line by MIS is associated with induction of the
      p16 tumor suppressor protein. However, in contrast to OVCAR8 cells, induction of
      p130 and p107 appears to play an important role in the inhibition of growth of
      C33A cells by MIS. Finally, normal cervical tissue expresses the MIS type II
      receptor in vivo, supporting the idea that MIS could be a targeted therapy for
      cervical cancer.

PMID- 14671317
TI  - p57(Kip2) cooperates with Nurr1 in developing dopamine cells.
AB  - Cyclin-dependent kinase inhibitors of the Cip/Kip family play critical roles in
      regulating cell proliferation during embryogenesis. However, these proteins also
      influence cell differentiation by mechanisms that have remained unknown. Here we
      show that p57Kip2 is expressed in postmitotic differentiating midbrain dopamine
      cells. Induction of p57Kip2 expression depends on Nurr1, an orphan nuclear
      receptor that is essential for dopamine neuron development. Moreover, analyses of
      p57Kip2 gene-targeted mice revealed that p57Kip2 is required for the maturation
      of midbrain dopamine neuronal cells. Additional experiments in a dopaminergic
      cell line demonstrated that p57Kip2 can promote maturation by a mechanism that
      does not require p57Kip2-mediated inhibition of cyclin-dependent kinases.
      Instead, evidence indicates that p57Kip2 functions by a direct protein-protein
      interaction with Nurr1. Thus, in addition to its established function in control
      of proliferation, these results reveal a mechanism whereby p57Kip2 influences
      postmitotic differentiation of dopamine neurons.

PMID- 14671318
TI  - Limited boundaries for extensive horizontal gene transfer among Salmonella
      pathogens.
AB  - Recombination is thought to be rare within Salmonella, as evidenced by absence of
      gene transfer among SARC strains that represent the broad genetic diversity of
      the eight primary subspecies of this common facultative intracellular pathogen.
      We adopted a phylogenetic approach to assess recombination within the mutS gene
      of 70 SARB strains, a genetically homogeneous population of Salmonella enterica
      subspecies I strains, which have in common the ability to infect warm-blooded
      animals. We report here that SARB strains show evidence for widespread
      recombinational exchange in contrast to results obtained with strains exhibiting
      species-level genetic variation. Besides extensive allele shuffling, SARB strains
      showed notably larger recombinagenic patch sizes for mutS (at least approximately
      1.1 kb) than previously reported for S. enterica SARC strains. Explaining these
      experimental dichotomies provides important insight for understanding microbial
      evolution, because they suggest likely ecologic and genetic barriers that limit
      extensive gene transfer in the feral setting.

PMID- 14671319
TI  - A macroscopic scale model of bacterial flagellar bundling.
AB  - Escherichia coli and other bacteria use rotating helical filaments to swim. Each
      cell typically has about four filaments, which bundle or disperse depending on
      the sense of motor rotation. To study the bundling process, we built a
      macroscopic scale model consisting of stepper motor-driven polymer helices in a
      tank filled with a high-viscosity silicone oil. The Reynolds number, the ratio of
      viscous to elastic stresses, and the helix geometry of our experimental model
      approximately match the corresponding quantities of the full-scale E. coli cells.
      We analyze digital video images of the rotating helices to show that the initial
      rate of bundling is proportional to the motor frequency and is independent of the
      characteristic relaxation time of the filament. We also determine which
      combinations of helix handedness and sense of motor rotation lead to bundling.

PMID- 14671320
TI  - Systematic, genome-wide identification of host genes affecting replication of a
      positive-strand RNA virus.
AB  - Positive-strand RNA viruses are the largest virus class and include many
      pathogens such as hepatitis C virus and the severe acute respiratory syndrome
      coronavirus (SARS). Brome mosaic virus (BMV) is a representative positive-strand
      RNA virus whose RNA replication, gene expression, and encapsidation have been
      reproduced in the yeast Saccharomyces cerevisiae. By using traditional yeast
      genetics, host genes have been identified that function in controlling BMV
      translation, selecting BMV RNAs as replication templates, activating the
      replication complex, maintaining a lipid composition required for membrane
      associated RNA replication, and other steps. To more globally and systematically
      identify such host factors, we used engineered BMV derivatives to assay viral RNA
      replication in each strain of an ordered, genome-wide set of yeast single-gene
      deletion mutants. Each deletion strain was transformed to express BMV replicase
      proteins and a BMV RNA replication template with the capsid gene replaced by a
      luciferase reporter. Luciferase expression, which is dependent on viral RNA
      replication and RNA-dependent mRNA synthesis, was measured in intact yeast cells.
      Approximately 4500 yeast deletion strains ( approximately 80% of yeast genes)
      were screened in duplicate and selected strains analyzed further. This functional
      genomics approach revealed nearly 100 genes whose absence inhibited or stimulated
      BMV RNA replication and/or gene expression by 3- to >25-fold. Several of these
      genes were shown previously to function in BMV replication, validating the
      approach. Newly identified genes include some in RNA, protein, or membrane
      modification pathways and genes of unknown function. The results further
      illuminate virus and cell pathways. Further refinement of virus screening likely
      will reveal contributions from additional host genes.

PMID- 14671321
TI  - Homeoprotein DLX-1 interacts with Smad4 and blocks a signaling pathway from
      activin A in hematopoietic cells.
AB  - In the transforming growth factor beta (TGF-beta) superfamily, activin A, TGF
      beta1, and bone morphogenic protein 4 (BMP-4) have various effects on
      hematopoiesis, including early mesodermo-hematogenesis. After these cytokines
      bind to their respective receptor, a regulatory Smad is phosphorylated and
      becomes associated with Smad4, the common Smad, and the resulting complex
      translocates to the nucleus to regulate transcription. DLX1 is the product of a
      member of the distal-less homeobox gene family, which is known to have important
      roles in embryogenesis, particularly in craniofacial development, and in
      GABAergic neurogenesis. DLX1 has been reported to be temporally and spatially
      coexpressed with BMP-4 during embryogenesis in selected contexts. We report here
      that, in addition to the previously reported regions/cells, DLX1 is expressed in
      hematopoietic cells in a lineage-dependent manner and that DLX1 interacts with
      Smad4 through its homeodomain. We show that it blocks multiple signals from TGF
      beta superfamily cytokines such as activin A, TGF-beta1, and BMP-4, including
      differentiation of a hematopoietic cell line by activin A. Taken together, these
      data suggest that DLX1 may function as a regulator of multiple signals from TGF
      beta superfamily members in broad biological contexts during blood production.

PMID- 14671322
TI  - A role for mechanosensitive channels in survival of stationary phase: regulation
      of channel expression by RpoS.
AB  - The mechanosensitive (MS) channels MscS and MscL are essential for the survival
      of hypoosmotic shock by Escherichia coli cells. We demonstrate that MscS and MscL
      are induced by osmotic stress and by entry into stationary phase. Reduced levels
      of MS proteins and reduced expression of mscL- and mscS-LacZ fusions in an rpoS
      mutant strain suggested that the RNA polymerase holoenzyme containing sigmaS is
      responsible, at least in part, for regulating production of MS channel proteins.
      Consistent with the model that the effect of sigmaS is direct, the MscS and MscL
      promoters both use RNA polymerase containing sigmaS in vitro. Conversely, clpP or
      rssB mutations, which cause enhanced levels of sigmaS, show increased MS channel
      protein synthesis. RpoS null mutants are sensitive to hypoosmotic shock upon
      entry into stationary phase. These data suggest that MscS and MscL are components
      of the RpoS regulon and play an important role in ensuring structural integrity
      in stationary phase bacteria.

PMID- 14671323
TI  - The early stages of duplicate gene evolution.
AB  - Gene duplications are one of the primary driving forces in the evolution of
      genomes and genetic systems. Gene duplicates account for 8-20% of the genes in
      eukaryotic genomes, and the rates of gene duplication are estimated at between
      0.2% and 2% per gene per million years. Duplicate genes are believed to be a
      major mechanism for the establishment of new gene functions and the generation of
      evolutionary novelty, yet very little is known about the early stages of the
      evolution of duplicated gene pairs. It is unclear, for example, to what extent
      selection, rather than neutral genetic drift, drives the fixation and early
      evolution of duplicate loci. Analysis of recently duplicated genes in the
      Arabidopsis thaliana genome reveals significantly reduced species-wide levels of
      nucleotide polymorphisms in the progenitor and/or duplicate gene copies,
      suggesting that selective sweeps accompany the initial stages of the evolution of
      these duplicated gene pairs. Our results support recent theoretical work that
      indicates that fates of duplicate gene pairs may be determined in the initial
      phases of duplicate gene evolution and that positive selection plays a prominent
      role in the evolutionary dynamics of the very early histories of duplicate
      nuclear genes.

PMID- 14671324
TI  - Activation of latent myostatin by the BMP-1/tolloid family of metalloproteinases.
AB  - Myostatin is a transforming growth factor beta family member that acts as a
      negative regulator of skeletal muscle growth. Myostatin circulates in the blood
      of adult mice in a noncovalently held complex with other proteins, including its
      propeptide, which maintain the C-terminal dimer in a latent, inactive state. This
      latent form of myostatin can be activated in vitro by treatment with acid;
      however, the mechanisms by which latent myostatin is activated in vivo are
      unknown. Here, we show that members of the bone morphogenetic protein-1/tolloid
      (BMP-1/TLD) family of metalloproteinases can cleave the myostatin propeptide in
      this complex and can thereby activate latent myostatin. Furthermore, we show that
      a mutant form of the propeptide resistant to cleavage by BMP-1/TLD proteinases
      can cause significant increases in muscle mass when injected into adult mice.
      These findings raise the possibility that members of the BMP-1/TLD family may be
      involved in activating latent myostatin in vivo and that molecules capable of
      inhibiting these proteinases may be effective agents for increasing muscle mass
      for both human therapeutic and agricultural applications.

PMID- 14671325
TI  - Direct observation of tiers in the energy landscape of a chromoprotein: a single
      molecule study.
AB  - Single-molecule spectroscopic techniques were applied to individual pigments
      embedded in a chromoprotein. A sensitive tool to monitor structural fluctuations
      of the protein backbone in the local environment of the chromophore is provided
      by recording the changes of the spectral positions of the pigment absorptions as
      a function of time. The data provide information about the organization of the
      energy landscape of the protein in tiers that can be characterized by an average
      barrier height. Additionally, a correlation between the average barrier height
      within a distinct tier and the time scale of the structural fluctuations is
      observed.

PMID- 14671326
TI  - Chemocyanin, a small basic protein from the lily stigma, induces pollen tube
      chemotropism.
AB  - In plant reproduction, pollination is an essential process that delivers the
      sperm through specialized extracellular matrices (ECM) of the pistil to the
      ovule. Although specific mechanisms of guidance for pollen tubes through the
      pistil are not known, the female tissues play a critical role in this event. Many
      studies have documented the existence of diffusible chemotropic factors in the
      lily stigma that can induce pollen tube chemotropism in vitro, but no molecules
      have been isolated to date. In this study, we identified a chemotropic compound
      from the stigma by use of biochemical methods. We purified a lily stigma protein
      that is active in an in vitro chemotropism assay by using cation exchange, gel
      filtration, and HPLC. Tryptic digestion of the protein yielded peptides that
      identified the protein as a plantacyanin (basic blue protein), and this was
      confirmed by cloning the cDNA from the lily stigma. Plantacyanins are small cell
      wall proteins of unknown function. The measured molecular mass by electrospray
      ionization ion source MS is 9898 Da, and the molecular mass of the mature protein
      (calculated from the cDNA) is 9900.2 Da. Activity of the lily plantacyanin (named
      chemocyanin) is enhanced in the presence of stigma/stylar cysteine-rich adhesin,
      previously identified as a pollen tube adhesin in the lily style.

PMID- 14671327
TI  - Fungal endophytes limit pathogen damage in a tropical tree.
AB  - Every plant species examined to date harbors endophytic fungi within its
      asymptomatic aerial tissues, such that endophytes represent a ubiquitous, yet
      cryptic, component of terrestrial plant communities. Fungal endophytes associated
      with leaves of woody angiosperms are especially diverse; yet, fundamental aspects
      of their interactions with hosts are unknown. In contrast to the relatively
      species-poor endophytes that are vertically transmitted and act as defensive
      mutualists of some temperate grasses, the diverse, horizontally transmitted
      endophytes of woody angiosperms are thought to contribute little to host defense.
      Here, we document high diversity, spatial structure, and host affinity among
      foliar endophytes associated with a tropical tree (Theobroma cacao, Malvaceae)
      across lowland Panama. We then show that inoculation of endophyte-free leaves
      with endophytes isolated frequently from naturally infected, asymptomatic hosts
      significantly decreases both leaf necrosis and leaf mortality when T. cacao
      seedlings are challenged with a major pathogen (Phytophthora sp.). In contrast to
      reports of fungal inoculation inducing systemic defense, we found that protection
      was primarily localized to endophyte-infected tissues. Further, endophyte
      mediated protection was greater in mature leaves, which bear less intrinsic
      defense against fungal pathogens than do young leaves. In vitro studies suggest
      that host affinity is mediated by leaf chemistry, and that protection may be
      mediated by direct interactions of endophytes with foliar pathogens. Together,
      these data demonstrate the capacity of diverse, horizontally transmitted
      endophytes of woody angiosperms to play an important but previously unappreciated
      role in host defense.

PMID- 14671328
TI  - Heterogeneity of rhythmic suprachiasmatic nucleus neurons: Implications for
      circadian waveform and photoperiodic encoding.
AB  - Circadian rhythms in neuronal ensemble, subpopulations, and single unit activity
      were recorded in the suprachiasmatic nuclei (SCN) of rat hypothalamic slices.
      Decomposition of the ensemble pattern revealed that neuronal subpopulations and
      single units within the SCN show surprisingly short periods of enhanced
      electrical activity of approximately 5 h and show maximal activity at different
      phases of the circadian cycle. The summed activity accounts for the neuronal
      ensemble pattern of the SCN, indicating that circadian waveform of electrical
      activity is a composed tissue property. The recorded single unit activity pattern
      was used to simulate the responsiveness of SCN neurons to different photoperiods.
      We inferred predictions on changes in peak width, amplitude, and peak time in the
      multiunit activity pattern and confirmed these predictions with hypothalamic
      slices from animals that had been kept in a short or long photoperiod. We propose
      that the animals' ability to code for day length derives from plasticity in the
      neuronal network of oscillating SCN neurons.

PMID- 14671330
TI  - Crystal structures that suggest late development of genetic code components for
      differentiating aromatic side chains.
AB  - Early forms of the genetic code likely generated "statistical" proteins, with
      similar side chains occupying the same sequence positions at different ratios. In
      this scenario, groups of related side chains were treated by aminoacyl-tRNA
      synthetases as a single molecular species until a discrimination mechanism
      developed that could separate them. The aromatic amino acids tryptophan,
      tyrosine, and phenylalanine likely constituted one of these groups. A crystal
      structure of human tryptophanyl-tRNA synthetase was solved at 2.1 A with a
      tryptophanyl-adenylate bound at the active site. A cocrystal structure of an
      active fragment of human tyrosyl-tRNA synthetase with its cognate amino acid
      analog was also solved at 1.6 A. The two structures enabled active site
      identifications and provided the information for structure-based sequence
      alignments of approximately 45 orthologs of each enzyme. Two critical positions
      shared by all tyrosyl-tRNA synthetases and tryptophanyl-tRNA synthetases for
      amino acid discrimination were identified. The variations at these two positions
      and phylogenetic analyses based on the structural information suggest that, in
      contrast to many other amino acids, discrimination of tyrosine from tryptophan
      occurred late in the development of the genetic code.

PMID- 14671329
TI  - Borrelia burgdorferi transcriptome in the central nervous system of non-human
      primates.
AB  - Neurological symptoms are common manifestations of Lyme disease; however, the
      paucibacillary nature of the spirochete in this environment has precluded a
      molecular analysis of the spirochete in the CNS. We have now adapted differential
      expression analysis by using a custom-amplified library (DECAL) in conjunction
      with Borrelia burgdorferi whole-genome and subgenome arrays to examine in vivo
      gene expression by B. burgdorferi in a non-human primate (NHP) model of
      neuroborreliosis. The expression profile of B. burgdorferi was examined in the
      CNS and heart of steroid-treated and immunocompetent NHPs. Eighty-six chromosomal
      genes and 80 plasmid-encoded genes were expressed at similar levels in the CNS
      and heart tissue of both immunocompetent and steroid-treated NHPs. The expression
      of 66 chromosomal genes and 32 plasmid-encoded genes was increased in the CNS of
      both immunocompetent and steroid-treated NHPs. It is likely that the expression
      of these genes is governed by physiological factors specific to the CNS milieu.
      However, 83 chromosomal and 114 plasmid-encoded genes showed contrasting
      expression profiles in steroid-treated and immunocompetent NHPs. The effect of
      dexamethasone on the immune status of the host as well as on the host metabolic
      pathways could contribute to these differences in the B. burgdorferi
      transcriptome. Results obtained herein underscore the complex interplay of host
      factors on B. burgdorferi gene expression in vivo. The results provide a global
      snapshot of the spirochetal transcriptome in the CNS and should spur the design
      of experiments aimed at understanding the molecular basis of neuroborreliosis.

PMID- 14671331
TI  - Ultrafast folding of alpha3D: a de novo designed three-helix bundle protein.
AB  - Here, we describe the folding/unfolding kinetics of alpha3D, a small designed
      three-helix bundle. Both IR temperature jump and ultrafast fluorescence mixing
      methods reveal a single-exponential process consistent with a minimal folding
      time of 3.2 +/- 1.2 micros (at approximately 50 degrees C), indicating that a
      protein can fold on the 1- to 5-micros time scale. Furthermore, the single
      exponential nature of the relaxation indicates that the prefactor for transition
      state (TS)-folding models is probably >or=1 (micros)-1 for a protein of this size
      and topology. Molecular dynamics simulations and IR spectroscopy provide a
      molecular rationale for the rapid, single-exponential folding of this protein.
      alpha3D shows a significant bias toward local helical structure in the thermally
      denatured state. The molecular dynamics-simulated TS ensemble is highly
      heterogeneous and dynamic, allowing access to the TS via multiple pathways.

PMID- 14671333
TI  - Twinned alpha-LiRb2(CF3SO3)3.
AB  - The investigated crystal of alpha-LiRb(2)(CF(3)SO(3))(3) [lithium dirubidium
      tris(trifluoromethanesulfonate)] was a twin, with the twin matrix given by (
      100/010/001). The structure consists of channel-like patterns built up of
      lipophilic CF(3) groups pointing towards each other. The polar interstices are
      occupied by cations. One Rb atom is coordinated by O atoms in the form of a
      distorted square antiprism, while the coordination around the second Rb atom is
      best described as a distorted pentagonal plane, with one O atom and one F atom
      situated above and an additional F atom below this plane. The O atoms around the
      Li atom form a strongly distorted tetrahedron.

PMID- 14671334
TI  - Lithium and sodium yttrium orthosilicate oxyapatite, LiY9(SiO4)6O2 and
      NaY9(SiO4)6O2, at both 100 K and near room temperature.
AB  - Lithium yttrium orthosilicate oxyapatite [lithium nonayttrium hexakis(silicate)
      dioxide], LiY(9)(SiO(4))(6)O(2), crystallizes in the centrosymmetric space group
      P6(3)/m at both 295 and 100 K. The structure closely resembles those of fluorine
      apatite and sodium yttrium orthosilicate oxyapatite [sodium nonayttrium
      hexakis(silicate) dioxide], NaY(9)(SiO(4))(6)O(2), which was also investigated,
      at 270 and 100 K, in this study. There are two different crystallographic sites
      for the Y(3+) ion, which are coordinated by seven and nine O atoms. One-fourth of
      the nine-coordinated site is occupied by Li or Na atoms, thus maintaining charge
      balance. The Si atom occupies a tetrahedral site. The two compounds show no
      symmetry change between room temperature and 100 K, and the alterations in
      structural parameters are small.

PMID- 14671335
TI  - Partial Sn-atom ordering in Sm3Ga0.80-2.48Sn4.20-2.52.
AB  - Trisamarium digallide tristannide crystallizes with a partially ordered
      Pu(3)Pd(5)-type structure in space group Cmcm. In a single crystal of
      Sm(3)Ga(1.89(4))Sn(3.11(4)), the 8g position is mostly occupied by Sn atoms (93%
      Sn and 7% Ga), while the 4c and 8f positions are occupied by a Ga/Sn statistical
      mixture. The evolution of the structure as a function of the Ga content has been
      studied by X-ray powder diffraction on ten Sm(3)Ga(5-x)Sn(x) samples. It is shown
      that the 8g position remains occupied essentially exclusively by Sn atoms within
      the whole homogeneity range, with x ranging from 2.52 to 4.20.

PMID- 14671332
TI  - A comprehensive analysis of hydrogen peroxide-induced gene expression in tobacco.
AB  - Hydrogen peroxide plays a central role in launching the defense response during
      stress in plants. To establish a molecular profile provoked by a sustained
      increase in hydrogen peroxide levels, catalase-deficient tobacco plants (CAT1AS)
      were exposed to high light (HL) intensities over a detailed time course. The
      expression kinetics of >14000 genes were monitored by using transcript profiling
      technology based on cDNA-amplified fragment length polymorphism. Clustering and
      sequence analysis of 713 differentially expressed transcript fragments revealed a
      transcriptional response that mimicked that reported during both biotic and
      abiotic stresses, including the up-regulation of genes involved in the
      hypersensitive response, vesicular transport, posttranscriptional processes,
      biosynthesis of ethylene and jasmonic acid, proteolysis, mitochondrial
      metabolism, and cell death, and was accompanied by a very rapid up-regulation of
      several signal transduction components. Expression profiling corroborated by
      functional experiments showed that HL induced photoinhibition in CAT1AS plants
      and that a short-term HL exposure of CAT1AS plants triggered an increased
      tolerance against a subsequent severe oxidative stress.

PMID- 14671336
TI  - A ferroelectric barium titanate, BaTi2O5.
AB  - The crystal structure of monobarium dititanium pentaoxide, BaTi(2)O(5),
      synthesized by a floating-zone method, was studied by X-ray diffraction. Previous
      reports describe the structure as being in the monoclinic centrosymmetric space
      group C2/m. We have recently found that this material exhibits ferroelectricity,
      and therefore BaTi(2)O(5) should have lower symmetry. The crystal structure of
      BaTi(2)O(5) was refined in space group C2, revealing a displacement of the Ti
      atoms along the b axis. This result is consistent with the fact that the
      ferroelectricity of BaTi(2)O(5) was only observed along the b axis.

PMID- 14671337
TI  - Lanthanum indium oxide from X-ray powder diffraction.
AB  - LaInO(3), a promising ion conductor for a holistic solid oxide fuel cell, was
      synthesized by a solid-state reaction method. The structure was refined by the
      Rietveld method using X-ray powder diffraction data. The structure of LaInO(3) is
      distorted by the in-phase and antiphase tilting of oxygen octahedra in the a(+)b(
      )b(-) system of the InO(6) polyhedra. In the Pmna space group, the In atom lies
      on an inversion centre and the La atom and one of the O atoms lie on a mirror
      plane.

PMID- 14671338
TI  - Vanadate garnet, Ca2NaMg2V3O12.
AB  - The vanadate garnet Ca(2)NaMg(2)V(3)O(12) (dicalcium sodium dimagnesium
      trivanadium dodecaoxide), synthesized by a floating zone method, has a notable
      structural feature in that the dodecahedral-dodecahedral shared edge length is
      longer than the unshared dodecahedral edge length. It is also noteworthy that the
      octahedral-dodecahedral shared edge length is as long as the unshared octahedral
      edge length. These unusual structural features are closely related to the weak
      repulsions between dodecahedral cations and between dodecahedral and octahedral
      cations.

PMID- 14671339
TI  - Magnesium diiodide, MgI2.
AB  - Single crystals of magnesium diiodide have been grown and the structure solved
      for the first time from single-crystal X-ray diffraction data. This study
      confirms that MgI(2) is isostructural with CdI(2) (C6 or 2H structure type). The
      space group is P-3m1 with the Mg atom on a site with 3m symmetry (Wyckoff site
      1a) and the I atom on a site with m symmetry (Wyckoff site 2d). Trends in the 2H
      structures of dihalides are discussed briefly.

PMID- 14671340
TI  - Superstructure of alpha-phase potassium nitrate.
AB  - The structure of potassium nitrate, KNO(3), has been redetermined at room
      temperature. The compound surprisingly shows a 2 x 2 x 1 superstructure and
      crystallizes in space group Cmc2(1). This result contrasts with that found in
      former investigations, which gave the supergroup Pmcn, neglecting the
      superstructure. The improved results are due to the employment of a CCD area
      detector.

PMID- 14671341
TI  - (eta6-2-Bromo-1,1'-biphenyl)-tricarbonylchromium.
AB  - The title compound, [Cr(C(12)H(9)Br)(CO)(3)], crystallizes in the triclinic space
      group P-1 with close Br.Br separations. These contacts, along with several other
      factors, influence the (Ph)C-C(o-BrC(6)H(4)) dihedral angle of 58.82 (6) degrees.
      The typical piano-stool coordination about the Cr atom is in excellent agreement
      with the results of density functional theory calculations.

PMID- 14671342
TI  - Two bismuth oxalate hydrates and revision of their chemical formulae.
AB  - The crystal structures of two bismuth(III) oxalate hydrates, previously described
      as 'Bi(2)(C(2)O(4))(3).H(2)C(2)O(4)' and 'Bi(2)(C(2)O(4))(3).7H(2)O', were solved
      and refined from single-crystal X-ray diffraction data. The results led to the
      revised chemical formulae Bi(2)(C(2)O(4))(3).6H(2)O and
      Bi(2)(C(2)O(4))(3).8H(2)O, respectively. Both dibismuth(III) trioxalate
      hexahydrate (tetraaquatri-micro-oxalato-dibismuth(III) dihydrate,
      [[Bi(2)(C(2)O(4))(3)(H(2)O)(4)].2H(2)O](n)) and dibismuth(III) trioxalate
      octahydrate (tetraaquatri-micro-oxalato-dibismuth(III) tetrahydrate
      [[Bi(2)(C(2)O(4))(3)(H(2)O)(4)].4H(2)O](n)) are characterized by a three
      dimensional network of Bi atoms connected by tetradentate oxalate groups. All
      ligand and 'free' water molecules are located in channels and voids. The mean Bi
      O bond lengths are approximately 2.51 A. The lone electron pairs on all Bi(3+)
      cations are stereochemically inactive.

PMID- 14671343
TI  - Group 2 metal salts of pyromellitic acid: [Mg(H2O)6](C10H4O8) and
      [Ba(C10H4O8)(H2O)5].
AB  - Structural determinations of the magnesium(II) and barium(II) salts of
      pyromellitic acid (benzene-1,2,4,5-tetracarboxylic acid) are presented.
      Hexaaquamagnesium(II) benzene-1,2,4,5-tetracarboxylate(2-),
      [Mg(H(2)O)(6)](C(10)H(4)O(8)), (I), and pentaaqua[benzene-1,2,4,5
      tetracarboxylato(2-)]barium(II), [Ba(C(10)H(4)O(8))(H(2)O)(5)], (II), are both
      centrosymmetric and both possess a 1:1 metal-ligand ratio, but the two structures
      are found to differ in that the magnesium salt contains a hexaaqua cation and
      possesses only hydrogen-bonding interactions between cations and anions, while
      the barium salt exhibits coordination of the carboxylate ligand to the nine
      coordinate metal centre. In (I), both ions sit on a 2/m site symmetry, and in
      (II), the cation and anion are located on m and i site symmetries, respectively.

PMID- 14671344
TI  - catena-Poly[potassium [copper(II)-mu-isothiocyanato-mu-N-salicylidene-beta
      alaninato2-]].
AB  - The title polymeric compound, catena-poly[dipotassium [bis[mu-N-salicylidene-beta
      alaninato(2-)]-kappa(4)O,N,O':O";kappa(4)O":O,N,O'-dicopper(II)]-di-mu
      isothiocyanato-kappa(2)N:S;kappa(2)S:N], [K[Cu(NCS)(C(10)H(9)NO(3))]](n),
      consists of [isothiocyanato(N-salicylidene-beta-alaninato)copper(II)](-) anions
      connected through the two three-atom thiocyanate (mu-NCS) and the two anti,anti
      mu-carboxylate bridges into infinite one-dimensional polymeric anions, with
      coulombically interacting K(+) counter-ions with coordination number 7
      constrained between the chains. The Cu(II) atoms adopt a distorted tetragonal
      bipyramidal coordination, with three donor atoms of the tridentate Schiff base
      and one N atom of the bridging mu-NCS ligand in the basal plane. The first axial
      position is occupied by a thiocyanate S atom of a symmetry-related mu-NCS ligand
      at an apical distance of 2.9770 (8) A, and the second position is occupied by an
      O atom of a bridging carboxylate group from an adjacent coordination unit at a
      distance of 2.639 (2) A.

PMID- 14671345
TI  - The effects of substitution on tetrakis(substituted imidazole)copper(II)
      trifluoromethanesulfonates.
AB  - The organic ligands 4-methyl-1H-imidazole and 2-ethyl-4-methyl-1H-imidazole react
      with Cu(CF(3)SO(3))(2).6H(2)O to give tetrakis(5-methyl-1H-imidazole
      kappaN(3))copper(II) bis(trifluoromethanesulfonate),
      [Cu(C(4)H(6)N(2))(4)](CF(3)SO(3))(2), and aquatetrakis(2-ethyl-5-methyl-1H
      imidazole-kappaN(3))copper(II) bis(tri fluoromethanesulfonate),
      [Cu(C(6)H(10)N(2))(4)(H(2)O)](CF(3)SO(3))(2). In the former, the Cu atom has an
      elongated octahedral coordination environment, with four imidazole rings in
      equatorial positions and two trifluoromethanesulfonate ions in axial positions.
      This conformation is similar to those in the analogous complexes
      tetrakis(imidazole)copper(II) trifluoromethanesulfonate and tetrakis(2-methyl-1H
      imidazole)copper(II) trifluoromethanesulfonate. In the second of the title
      compounds, the ethyl groups block the central Cu atom, and a square-pyramidal
      coordination environment is formed around the Cu atom, with the substituted
      imidazole rings in the basal positions and a water molecule in the axial
      position.

PMID- 14671346
TI  - trans-Diaquabis(1H-imidazole-4,5-dicarboxylate-kappa2N3,O4)manganese(II).
AB  - In the title compound, [Mn(C(5)H(3)N(2)O(4))(2)(H(2)O)(2)], the Mn(II) atom lies
      on an inversion centre, is trans-coordinated by two N,O-bidentate 1H-imidazole
      4,5-dicarboxylate monoanionic ligands [Mn-O = 2.202 (3) A and Mn-N = 2.201 (4) A]
      and two water molecules [Mn-O = 2.197 (4) A], and exhibits a distorted octahedral
      geometry, with adjacent cis angles of 76.45 (13), 86.09 (13) and 89.20 (13)
      degrees. The complete solid-state structure can be described as a three
      dimensional supramolecular framework, stabilized by extensive hydrogen-bonding
      interactions involving the coordinated water molecules, the carboxy O atoms and
      the protonated imidazole N atoms of the imidazole-4,5-dicarboxylate ligands.

PMID- 14671347
TI  - Di-mu-cyanato-bis[(cyanato-kappaN)(tetramethylethylenediamine
      kappa2N,N')copper(II)] and catena-poly[[mu3-cyanato-kappa3O:N:N-bis[(cyanato
      kappaN)(1,3-diaminopropane-kappa2N,N')copper(II)]]-mu3-cyanato-kappa3N:N:O].
AB  - The two title Cu(II) complexes, [Cu(2)(NCO)(4)(tmeda)(2)] (tmeda is
      tetramethylethylenediamine, C(6)H(16)N(2)), (I), and [Cu(NCO)(2)(pn)](n) (pn is
      1,3-diaminopropane, C(3)H(10)N(2)), (II), have been synthesized and their crystal
      structures determined. In (I), which lies about an inversion centre, each Cu
      centre possesses a distorted tetragonal-pyramidal geometry with four basal N
      atoms from two cyanate anions [Cu-N = 1.945 (2) and 1.948 (3) A] and one tmeda
      molecule [Cu-N = 2.053 (2) and 2.071 (2) A], and one axial O atom [Cu-O = 2.737
      (3) A] from another cyanate anion. The two neighbouring Cu atoms in (I) are
      joined by a pair of cyanates in an end-to-end fashion, forming a dimer. In (II),
      each Cu centre adopts a distorted square-bipyramidal geometry, with four
      equatorial N atoms from two cyanates [Cu-N = 1.988 (2) and 2.007 (3) A] and a pn
      ligand [Cu-N = 1.996 (3) and 2.011 (3) A], and one apical N atom [Cu-N = 2.437
      (3) A] and an apical O atom [Cu-O = 2.900 (3) A] from two cyanates. In contrast
      with (I), the two neighbouring Cu atoms in (II) are bridged by two cyanates in an
      end-on fashion, to form a centrosymmetric dimeric unit. These units are further
      crosslinked, forming a two-dimensional network structure, via weak interactions
      between the bridging cyanate O atom and a neighbouring Cu atom, plus interactions
      of the amine H atoms with the cyanate O atoms and the terminal cyanate N atom.

PMID- 14671348
TI  - Bis(di-2-pyridylphosphinato-kappa3N,O,N')copper(II) dichloromethane disolvate.
AB  - The solid-state structure of the first reported homoleptic copper di-2
      pyridylphosphinate complex shows an extremely large 'z-out' tetragonal
      distortion, with an axial Cu.O distance of 2.430 (2) A. The title complex,
      [Cu(C(10)H(8)N(2)O(2)P)(2)].2CH(2)Cl(2) or Cu[py(2)P(O)O](2).2CH(2)Cl(2),
      comprises two di-2-pyridylphosphinate ligands coordinated to the central
      copper(II) ion, which sits on an inversion center. The pyridyl rings of one
      ligand are trans to the pyridyl rings of their symmetry-related counterpart. The
      two trans py-Cu-py moieties are coplanar, as required by the inversion symmetry.
      A disordered dichloromethane solvent molecule is cocrystallized in the asymmetric
      unit cell.

PMID- 14671349
TI  - Isomorphous dichloro- and dibromo(2-methyl-2-phenylpropyl)phenylstannane, both
      displaying the same intramolecular pi-pi interaction at 120 K.
AB  - The title compounds, dichloro- and dibromoneophylphenyltin,
      [SnCl(2)(C(6)H(5))(C(10)H(13))] and [SnBr(2)(C(6)H(5))(C(10)H(13))],
      respectively, are remarkable for the 'U' shape of the molecules, whereby the two
      phenyl groups are brought face-to-face in an arrangement that permits
      intermolecular C-H.pi bonds to connect the molecules into layers parallel to
      (100). Intermolecular Sn-halide bonds are notably absent from the structures.

PMID- 14671350
TI  - [mu-3,4'-Bi-1,2,4-triazole-di-micro-chloro-copper(II) monohydrate].
AB  - In the title compound, mu-3,4'-bi-1,2,4-triazole-di-mu-chloro-copper(II)
      monohydrate, [[CuCl(2)(C(4)H(4)N(6))].H(2)O](n), the Cu atom is located in a
      distorted octahedron consisting of two N atoms and four Cl atoms. The structural
      unit is an infinite chain in which octahedral groups, connected by shared edges,
      are also linked by bitriazole molecules. The bitriazole ligand, the Cu atom and
      the water O atom all lie on independent twofold axes. The structure is held
      together by hydrogen bonds between the water molecules and the non-coordinated N
      atoms of the ligand, and by van der Waals forces.

PMID- 14671351
TI  - trans-Cyano(6-methyl-1,4,8,11-tetraazacyclotetradecan-6-amine)cobalt(III)
      bis(perchlorate) hydrate and trans-hydroxo(6-methyl-1,4,8,11
      tetraazacyclotetradecan-6-amine)cobalt(III) bis(perchlorate).
AB  - The crystal structures of a pair of closely related macrocyclic cyano- and
      hydroxopentaaminecobalt(III) complexes, as their perchlorate salts, are reported.
      Although the two complexes, [Co(CN)(C(11)H(27)N(5))](ClO(4))(2).H(2)O and
      [Co(OH)(C(11)H(27)N(5))](ClO(4))(2), exhibit similar conformations, significant
      differences in the Co-N bond lengths arise from the influence of the sixth ligand
      (cyano as opposed to hydroxo). The ensuing hydrogen-bonding patterns are also
      distinctly different. Disorder in the perchlorate anions was clearly resolved and
      this was rationalized on the basis of distinct hydrogen-bonding motifs involving
      the anion O atoms and the N-H and O-H donors.

PMID- 14671352
TI  - Di-micro-benzoato-bis[dicarbonyl(pyridine)ruthenium(I)] (new polymorph) and di-mu
      trifluoroacetato-bis[dicarbonyl(pyridine)ruthenium(I)].
AB  - The syntheses and crystal structure determinations of a pair of 'sawhorse' dimers
      are reported, viz. [Ru(2)(C(6)H(5)CO(2))(2)(C(5)H(5)N)(2)(CO)(4)] [a new
      polymorph, cf. Kepert, Deacon, Spiccia, Fallon, Skelton & White (2000). J. Chem.
      Soc. Dalton Trans. pp. 2867-2874] and
      [Ru(2)(CF(3)CO(2))(2)(C(5)H(5)N)(2)(CO)(4)]. The Ru.Ru distances are 2.6724 (2)
      and 2.7122 (5) A, respectively.

PMID- 14671353
TI  - [[Ca5(C8H4O4)5(H2O)9].8H2O]n: the first crystallographically characterized non
      transition metal salt of isophthalic acid.
AB  - The reaction of CaCO3 with isophthalic acid in water yields nonaaquapenta-mu
      isophthalato-pentacalcium octahydrate,
      [[Ca(5)(C(8)H(4)O(4))(5)(H(2)O)(9)].8H(2)O](n), a complex polymeric one
      dimensional column structure bearing metal-carboxylate bonds and Ca-bound
      terminal and bridging water molecules, in addition to hydrogen-bonded water
      molecules of crystallization. The asymmetric unit comprises half of the formula
      unit, with one Ca(2+) ion located on a twofold axis, and contains 16 unique
      strong O-H.O hydrogen bonds, some of which link the columns together.

PMID- 14671354
TI  - Alendronate zwitterions bind to calcium cations arranged in columns.
AB  - Alendronate is used clinically in the treatment of skeletal disorders, the mode
      of action depending on the adsorption to calcium hydroxyapatite crystals (bone).
      In the title compound, calcium 4-ammonium-1-hydroxybutylidene-1,1-bisphosphonate,
      Ca(2+).2C(4)H(12)NO(7)P(2)(-), alendronate is a zwitterion, possessing one
      negative charge on each PO(3) group and a protonated N atom. The zwitterion is
      disposed with its negative end facing the Ca(2+) ion, while its positive end is
      stretched in the opposite direction. The geometry of the carbon chain is all
      trans, while the hydroxy group is approximately gauche. The Ca(2+) ion lies on a
      twofold axis parallel to b. The coordination sphere around the metal cation is
      octahedral and is determined by monodentate- and bidentate-coordinated
      alendronate zwitterions. The O.O bite distance is 3.080 (2) A. Coordinated Ca(2+)
      metal cations are arranged at the centre of a column running along c.

PMID- 14671355
TI  - Catena-poly[[trans-bis(ethane-1,2-diamine-kappa2N,N')copper(II)]-micro-dithionato
      kappa2O:O'] and trans-diaquabis(propane-1,3-diamine-kappa2N,N')copper(II)
      dithionate.
AB  - In title anhydrous catena-poly[[trans-bis(ethane-1,2-diamine
      kappa(2)N,N')copper(II)]-micro-dithionato-kappa(2)O:O'],
      [Cu(S(2)O(6))(C(2)H(8)N(2))(2)](n) or
      [[H(2)N(CH(2))(2)NH(2)](2)Cu(O.O(2)SSO(2).O)]( infinity ), successive Cu atoms
      are bridged by a single doubly charged dithionate group, forming a one
      dimensional polymer with inversion centres at the metal atoms and the mid-point
      of the S-S bond [Cu-O = 2.5744 (15) A]. In title (hydrated) trans
      diaquabis(propane-1,3-diamine-kappa(2)N,N')copper(II) dithionate,
      [Cu(C(3)H(10)N(2))(2)(H(2)O)(2)](S(2)O(6)) or
      [[H(2)N(CH(2))(3)NH(2)](2)Cu(OH(2))(2)](S(2)O(6)), both ions have imposed 2/m
      symmetry. The 'axial' anion components are displaced by a pair of water ligands
      [Cu-O = 2.439 (3) A], the shorter Cu-O distance being compensated by the
      lengthened Cu-N distance [2.0443 (18), cf. 2.0100 (13) and 2.0122 (16) A].

PMID- 14671356
TI  - A magnesium-bis(diaryldiketiminate) complex.
AB  - The 1:1 of reaction of dibutylmagnesium with the ligand 2-[(2
      isopropylphenyl)amino]-4-[(2-isopropylphenyl)imino]pent-2-ene gives only the 1:2
      metal-ligand compound bis[N,N'-bis(2-isopropylphenyl)pentane-2,4
      diiminato]magnesium(II), [Mg(C(23)H(29)N(2))(2)], as an isolated solid. The
      coordination geometry about the Mg atom is distorted tetrahedral [N-Mg-N angles
      range from 90.73 (5) to 136.40 (6) degrees ], with the metal lying out of the
      ligand plane. The ligands themselves have non-crystallographic C(s) geometry. The
      structure is isotypic with the Zn analogue, and the small differences between
      these two structures provide evidence for a significant covalent contribution to
      bonds that are generally described as largely ionic.

PMID- 14671357
TI  - Intermolecular interactions in N-(ferrocenylmethyl)anthracene-9-carboxamide.
AB  - The title compound, [Fe(C(5)H(5))(C(21)H(16)NO)], was synthesized from the
      coupling reaction of anthracene-9-carboxylic acid and ferrocenylmethylamine. The
      ferrocenyl (Fc) group and the anthracene ring system both lie approximately
      orthogonal to the amide moiety. An amide-amide interaction (along the a axis) is
      the principal interaction [N.O = 2.910 (2) A]. A C-H.pi(arene) interaction
      [C.centroid = 3.573 (2) A] and a C-H.O interaction [C.O = 3.275 (3) A] complete
      the hydrogen bonding; two short (Fc)C.C(anthracene) contacts are also present.

PMID- 14671358
TI  - Bis[(2,2-dimethyl-1,3-propanediamine-kappa2N,N')(piperidine-2-carboxylato
      kappa2N,O)platinum(II)] sulfate.
AB  - The title compound, [Pt(C(6)H(10)NO(2))(C(5)H(14)N(2))](2)(SO(4)), crystallizes
      with two cations in the asymmetric unit. The two complex cations, which have a
      square-planar Pt(II) coordination, are chemically identical but differ slightly
      in the conformations of their amine groups. A neutral complex, viz. (2,2-dimethyl
      1,3-propanediamine-kappa(2)N,N')bis(2-piperidinecarboxylato-kappaN)platinum(II),
      is shown to form in solution and to change rapidly into the title compound.

PMID- 14671359
TI  - [N,N'-Bis(3-aminopropyl)ethylenediamine-kappa4N,N',N",N"'](trithiocyanurato
      kappa2N,S)zinc(II) ethanol solvate.
AB  - In the crystal structure of the title compound, [N,N'-bis(3
      aminopropyl)ethylenediamine-kappa(4)N,N',N",N"'][1,3,5-triazine-2,4,6(1H,3H,5H)
      trithionato(2-)-kappa(2)N,S]zinc(II) ethanol solvate,
      [Zn(C(8)H(22)N(4))(2)(C(3)HN(3)S(3))].C(2)H(6)O, the Zn(II) atom is octahedrally
      coordinated by four N atoms [Zn-N = 2.104 (2)-2.203 (2) A] of a tetradentate N
      donor N,N'-bis(3-aminopropyl)ethylenediamine (bapen) ligand and by two S and N
      atoms [Zn-S = 2.5700 (7) A and Zn-N = 2.313 (2) A] of a trithiocyanurate(2-)
      (ttcH(2-)) dianion bonded as a bidentate ligand in a cis configuration. The
      crystal structure of the compound is stabilized by a network of hydrogen bonds.

PMID- 14671360
TI  - Two new soluble iron-oxo complexes: [Fe2(mu-O)(mu-O2CCF3)2(O2CCF3)2(C10H8N2)2]
      and [Fe4(mu3-O)2(mu-O2CCF3)6(O2CCF3)2(C10H8N2)2].CF3CO2H.
AB  - Two new iron-oxo clusters, viz. di-mu-trifluoroacetato-mu-oxo-bis[(2,2'
      bipyridine-kappa(2)N,N')(trifluoroacetato-kappaO)iron(III)],
      [Fe(2)O(CF(3)CO(2))(4)(C(10)H(8)N(2))(2)], and bis(2,2'-bipyridine)di-mu(3)-oxo
      hexa-mu-trifluoroacetato-bis(trifluoroacetato)tetrairon(III) trifluoroacetic acid
      solvate, [Fe(4)O(2)(CF(3)CO(2))(8)(C(10)H(8)N(2))(2)].CF(3)CO(2)H, contain
      dinuclear and tetranuclear Fe(III) cores, respectively. The Fe(III) atoms are in
      distorted octahedral environments in both compounds and are linked by oxide and
      trifluoroacetate ions. The trifluoroacetate ions are either bridging (bidentate)
      or coordinated to the Fe(III) atoms via one O atom only. The fluorinated
      peripheries enhance the solubility of these compounds. Formal charges for all the
      Fe centers were assigned by summing valences of the chemical bonds to the Fe(III)
      atom.

PMID- 14671361
TI  - Dicyano[[(1S)-(1-phenylethyl)aziridin-2-yl]methanolato-kappa2N,O]boron.
AB  - In the title compound, C(13)H(14)BN(3)O, the aziridine ring is an almost
      equilateral triangle, the C-C distance being slightly shorter than the C-N
      distances, probably because of the dative B-N bond. The five-membered ring,
      composed of two C atoms and N, B and O atoms, is fused with the aziridine ring to
      form a six-membered ring with a chair conformation.

PMID- 14671362
TI  - Head-to-head dimers in the zwitterion of 1-hydroxy-1-phosphono-3-(1
      piperidino)propylidene-1-phosphonate (PHPBP).
AB  - The title compound, C(8)H(19)NO(7)P(2), is a member of the bisphosphonate family
      of therapeutic compounds. PHPBP has inner-salt character, consisting of a
      negatively charged PO(3) group and a positively charged N atom. The six-membered
      piperidine ring adopts an almost-perfect chair conformation. The hydroxyl group
      and the N atom have gauche and trans conformations in relation to the O-C-C-C-N
      backbone, respectively. Hydrogen bonding is the main contributor to the packing
      in the crystal, which consists of head-to-head dimers formed through phosphonyl
      phosphonyl hydrogen bonds, while O-H.O and N-H.O interactions join the dimers
      into a plane parallel to crystallographic b and c axes.

PMID- 14671363
TI  - Redetermination of sperminium tetrachloride.
AB  - In the title compound, 1,5,10,14-tetraazoniatetradecane tetrachloride,
      C(10)H(30)N(4)(4+).4Cl(-), the sperminium tetracation lies on a centre of
      symmetry. The two central C-N-C-C torsion angles are gauche and of opposite
      signs, and all the other torsion angles are trans. All NH groups participate in
      the three-dimensional hydrogen-bond network, which is additionally strengthened
      by C-H.Cl interactions.

PMID- 14671364
TI  - 2,2'-Methylenebis(3-hydroxy-5,5-dimethylcyclohex-2-en-1-one).
AB  - The title compound, C(17)H(24)O(4), crystallizes with two independent molecules,
      both lying across twofold rotation axes in space group Pccn, in a unit cell whose
      dimensions closely mimic those of a tetragonal cell. Each molecule contains
      paired O-H.O hydrogen bonds [H.O = 1.81 and 1.83 A, O.O = 2.640 (2) and 2.642 (2)
      A, and O-H.O = 168 and 162 degrees ].

PMID- 14671365
TI  - 2-Aminobenzimidazolium O-ethyl malonate: eight independent N-H...O hydrogen bonds
      generate sheets.
AB  - The title compound, C(7)H(8)N(3)(+).C(5)H(7)O(4)(-), crystallizes with Z' = 2 in
      space group P2(1)/c; eight independent N-H.O hydrogen bonds [H.O = 1.75-1.88 A,
      N.O = 2.699 (2)-2.829 (2) A and N-H.O = 147-179 degrees ] link the four
      independent ions into sheets.

PMID- 14671366
TI  - Self-recognition in a flexible bis(pyrrole) Schiff base derivative: formation of
      a one-dimensional hydrogen-bonded polymer.
AB  - The title Schiff base compound, N,N'-bis(pyrrol-2-ylmethylene)propane-1,2
      diamine, C(13)H(16)N(4), forms an interesting supramolecular structure (a one
      dimensional ladder-like polymer) in the solid state that is based on the
      existence of complementary intermolecular N-H.N=C hydrogen bonds between the
      monomer units. The polymer axis is collinear with the c axis of the orthorhombic
      unit cell. Quantum-chemical AM1 calculations clearly indicate that self
      recognition in this system by hydrogen bonding is favoured on electrostatic
      grounds, since the partial atomic charge on the H atom of the pyrrole NH group
      (0.274 e) complements the partial atomic charge of the N atom of the C=N group (
      0.239 e) on a neighbouring molecule.

PMID- 14671367
TI  - Two biologically active thiophene-3-carboxamide derivatives.
AB  - The two title compounds, 2-([(1Z)-[4-(dimethylamino)phenyl]methylene]amino)-4,5
      dimethyl-N-(2-methylphenyl)thiophene-3-carboxamide, C(23)H(25)N(3)OS, (I), and 2
      ([(1E)-[4-(dimethylamino)phenyl]methylene]amino)-N-(4-methylphenyl)-4,5,6,7
      tetrahydro-1-benzothiophene-3-carboxamide,C(25)H(27)N(3)OS, (II), show
      antibacterial and antifungal activities. The asymmetric unit of (II) contains two
      crystallographically independent molecules. The o-toluidine ring in (I) lies
      gauche with respect to the thiophene ring. In (II), the p-toluidine ring is
      coplanar with the thiophene ring in one molecule, but is tilted from it in the
      other molecule. Neither structure exhibits any significant intermolecular
      interactions, but in both, an intramolecular N-H.N hydrogen bond forms a pseudo
      six-membered ring, thus locking the molecular conformation and removing
      conformational flexibility.

PMID- 14671368
TI  - (+/-)-cis-2-Methyl-4-oxocyclohexanecarboxylic acid: catemeric hydrogen bonding in
      a delta-keto acid derived from Hagemann's ester.
AB  - The title compound, C(8)H(12)O(3), crystallizes as acid-to-ketone hydrogen
      bonding catemers, in which hydrogen bonds progress from the carboxyl group of
      each molecule to the ketone group of a translationally related neighbor [O.O =
      2.738 (3) A and O-H.O = 153 (4) degrees ]. Four separate hydrogen-bonding chains
      proceed through the cell in centrosymmetrically related pairs along axes lying in
      the ab plane. Three intermolecular C-H.O close contacts exist involving both
      carboxyl O atoms. Factors contributing to the choice of hydrogen-bonding mode are
      discussed.

PMID- 14671369
TI  - Uncovering stereochemical relations in a compound with a stereogenic N-O axis:
      methyl 2-(4-methyl-2-thioxo-2,3-dihydrothiazol-3-yloxy)propanoate.
AB  - The geometry of racemic methyl 2-(4-methyl-2-thioxo-2,3-dihydrothiazol-3
      yloxy)propanoate, C(8)H(11)NO(3)S(2), (I), is characterized by a distorted
      heterocyclic five-membered ring and an enantiomorphic N-alkoxy substituent, which
      is inclined at an angle of -68.8 degrees to the thiazolethione plane in (M)-(I).
      The unit cell consists of a 1:1 ratio of R,P- and S,M-configured molecules of
      (I). The combination of a P configuration at the N-O axis and an R configuration
      at the asymmetric propanoate C(beta) atom on one side, and an S,M configuration
      on the other side, is considered to originate from steric interactions. The
      largest substituent at the asymmetric propanoate C(beta) atom, i.e. the
      methoxycarbonyl group, resides above the methyl substituent; the medium-sized
      propanoate gamma-methyl substituent points in the opposite direction with respect
      to the N-O bond, whereas the H atom is located above the C=S double bond of the
      thiazolethione subunit.

PMID- 14671370
TI  - 2-Chloro-4,6-dimethoxy-1,3,5-triazine.
AB  - The molecules of 2-chloro-4,6-dimethoxy-1,3,5-triazine, C(5)H(6)ClN(3)O(2), lie
      on a crystallographic mirror plane. There is a close contact of 3.180 (3) A
      between one of the methyl C atoms and the N atom of a neighboring molecule.
      Differential scanning calorimetry measurements show that methyl rearrangement
      does not take place in the solid state, despite the close proximity of the methyl
      group to the N atom.

PMID- 14671371
TI  - Derivatives of 2,4-dimethoxy-1,3,5-triazine.
AB  - The crystal structure of three derivatives of 2,4-dimethoxy-1,3,5-triazine are
      described. In 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)morpholine, C(9)H(14)N(4)O(3),
      the morpholine moiety adopts a chair conformation, and the dimethoxytriazine
      molecule adopts a butterfly conformation with respect to the two methoxy groups.
      In 3-(4,6-dimethoxy-1,3,5-triazin-2-yloxy)-2-methylphenol, C(12)H(13)N(3)O(4),
      the dimethoxytriazine moiety adopts a propeller conformation with respect to the
      methoxy groups, and the molecules form dimers held together by O-H.N hydrogen
      bonds. 4-(4,6-Dimethoxy-1,3,5-triazin-2-yloxy)phenyl phenyl ketone,
      C(18)H(15)N(3)O(4), crystallizes with two crystallographically independent
      molecules in the asymmetric unit. The two molecules adopt different conformations
      with respect to the geometric relations between the phenyl ketone and triazine
      moieties.

PMID- 14671372
TI  - Two derivatives of 5-aminotetrazole: 5-amino-1-phenyltetrazole and 5-amino-1-(1
      naphthyl)tetrazole.
AB  - In the molecules of 5-amino-1-phenyltetrazole, C(7)H(7)N(5), (I), and 5-amino-1
      (1-naphthyl)tetrazole, C(11)H(9)N(5), (II), the tetrazole rings and aryl
      fragments are not coplanar; corresponding dihedral angles are 50.58 (5) and 45.19
      (7) degrees for the two independent molecules of (I), and 64.14 (5) degrees for
      (II). Intermolecular N-H.N hydrogen bonds between the amino groups and tetrazole
      N atoms are primarily responsible for formation of two-dimensional networks
      extending parallel to the bc plane in both compounds. The presence of the amino
      group has a distinct effect on the geometry of the tetrazole rings in each case.

PMID- 14671373
TI  - Betainohydroxamic acid chloride.
AB  - The title compound, N-hydroxy-2-(trimethylammonio)acetamide chloride,
      C(5)H(13)N(2)O(2)(+).Cl(-), has been synthesized and structurally characterized.
      The structure consists of betainohydroxamic acid cations and Cl(-) anions linked
      by N-H.Cl and O-H.Cl hydrogen bonds into chains along [001]. It was found that
      the positive inductive effect of the charged N atom in close proximity to the
      hydroxamate carbonyl O atom has a negligible effect on the hydroxamic C-N bond
      length.

PMID- 14671374
TI  - 2-Amino-6-(1-imidazolylmethyl)-4-(3,5,5-trimethyl-2-pyrazolin-1-yl)-1,3,5
      triazine and 2-amino-6-(1-benzimidazolylmethyl)-4-(3,5,5-trimethyl-2-pyrazolin-1
      yl)-1,3,5-triazine hemihydrate.
AB  - The two title compounds, C(13)H(18)N(8) and C(17)H(20)N(8).0.5H(2)O, possess
      similar molecular shapes, with the pyrazoline moiety and s-triazine ring located
      approximately in one plane, and the imidazole or benzimidazole ring nearly
      perpendicular to the s-triazine nucleus. In both crystal structures, despite
      there being a large number of accessible hydrogen-bond acceptor sites, only one H
      atom from the NH(2) group is involved in hydrogen bonding; the molecules are
      assembled into discrete centrosymmetric dimers via a pair of nearly linear N-H.N
      hydrogen bonds.

PMID- 14671375
TI  - Bis(2,5-dimethoxy-4-methylphenyl)methane and bis(2,5-dimethoxy-3,4,6
      trimethylphenyl)methane.
AB  - Bis(2,5-dimethoxy-4-methylphenyl)methane, C(19)H(24)O(4), (IIa), was obtained and
      characterized as a minor product from the reaction of toluhydroquinone dimethyl
      ether (1,4-dimethoxy-2-methylbenzene) with N-(hydroxymethyl)trifluoroacetamide.
      Similarly, bis(2,5-dimethoxy-3,4,6-trimethylphenyl)methane, C(23)H(32)O(4),
      (IIb), was prepared from the corresponding reaction of trimethylhydroquinone
      dimethyl ether (2,5-dimethoxy-1,3,4-trimethylbenzene). The molecules of (IIa) and
      (IIb) each lie on a twofold axis passing through the methylene group. The
      dihedral angle between the planar phenyl rings is 73.4 (1) degrees in (IIa) and
      77.9 (1) degrees in (IIb). The external bond angles around the bridging methylene
      group are 116.6 (2) and 117.3 (2) degrees for (IIa) and (IIb), respectively. In
      (IIa), the methoxy substituents lie in the plane of the ring and are conjugated
      with the aromatic system, whereas in (IIb), they are almost perpendicular to the
      phenyl ring and are positioned on opposite sides.

PMID- 14671376
TI  - 3-(4-Chlorobenzoyl)-7-(N,N-dimethylamino)-1-phenylindolizine and 3-(2,4
      dichlorobenzoyl)-7-(N,N-dimethylamino)-1-phenylindolizine.
AB  - In both of the title compounds, C(23)H(19)ClN(2)O, (I), and C(23)H(18)Cl(2)N(2)O,
      (II), the molecular packing is influenced by weak intermolecular C-H.O and C-H.pi
      interactions, but despite the chemical similarity of the compounds, the packing
      in (II) is entirely different from that observed in (I).

PMID- 14671377
TI  - 4,4'-Sulfonylbis[N-(4-nitrophenylmethylene)benzenamine]: whole-molecule disorder.
AB  - The crystal structure of the title compound, C(26)H(18)N(4)O(6)S, determined from
      synchrotron data with a small crystal, is characterized by the presence of whole
      molecule disorder. In each molecule, the two planar portions are approximately
      perpendicular to one another and there are short intermolecular contacts between
      the nitro groups.

PMID- 14671378
TI  - Anilinium monohydrogen DL-malate.
AB  - Crystals of the title salt, [(C(6)H(5)NH(3))](+).[(HOOC(CH(2))CH(OH)COO)](-) or
      C(6)H(8)N(+).C(4)H(5)O(5)(-), are built up from protonated anilinium residues and
      monodissociated DL-malate ions. The NH(3)(+) group of the anilinium cation is
      ordered at room temperature. Rotation of the NH(3)(+) group along the C(aromatic)
      Nsp(3) bond (often observed at room temperature in other anilinium salts) is
      prevented by N-H.O hydrogen bonds between the NH(3)(+) group and the malate
      anions. The anions are connected by four O-H.O hydrogen bonds into two
      dimensional sheets parallel to the (001) plane. The charged moieties, i.e. the
      anilinium cations and the sheets of hydrogen-bonded malate anions, form two
      dimensional layers in which the phenyl rings of the anilinium residues lie
      perpendicular to the malate-ion sheets. The conformation of the monodissociated
      malate ion in the crystal is compared with that obtained from ab initio molecular
      orbital calculations.

PMID- 14671379
TI  - ap-9-(o-Methylphenyl)-9-fluorenol, a structure exhibiting several aryl
      H...pi(arene) intermolecular interactions.
AB  - The title compound, C(20)H(16)O, (I), which crystallized exclusively as its ap
      rotamer, exhibits several intermolecular aryl-H.pi(arene) interactions, resulting
      in planar molecular arrays in which each molecule interacts with six adjacent
      molecules. Surprisingly, there were no O-H.O-H or O-H.pi(arene) interactions
      within hydrogen-bonding distances. Crystalline (I) melted sharply without
      molecular decomposition (NMR), but the cooled melt recrystallized only after
      several hours.

PMID- 14671380
TI  - 2-Phenylmalonpiperadide and 2-phenylmalonmorpholide.
AB  - The structures of 2-phenylmalonpiperadide [systematic name: 2-phenyl-1,3
      bis(piperidin-1-yl)propane-1,3-dione, C(19)H(26)N(2)O(2), (I)] and 2
      phenylmalonmorpholide [systematic name: 1,3-dimorpholino-2-phenylpropane-1,3
      dione, C(17)H(22)N(2)O(4), (II)], have been determined and both their molecular
      conformations and packing arrangements compared. Although chemically similar,
      compounds (I) and (II) exhibit different molecular conformations. The only
      general conformational similarities are that their respective carbonyl groups are
      orientated in the same direction and the heterocyclic rings exist in the chair
      arrangement. General similarities in the packing arrangements arise due to both
      compounds having the same space group (P2(1)2(1)2(1)) and a similar alignment of
      their phenyl-substituted backbone with respect to the c axis. Similar C-H.O
      hydrogen-bonding associations are listed for the carbonyl O atoms, while only one
      of the morpholine O atoms is involved in any such association.

PMID- 14671381
TI  - Acetamidoxime.
AB  - The oxime of acetamide, viz. N-hydroxyethanimidamide, C(2)H(6)N(2)O, has a
      complex hydrogen-bonding arrangement in its crystal structure, featuring one
      strong O-H.N hydrogen bond together with weaker hydrogen bonding involving the
      amide groups. Conjugation effects lead to atypical distances and angles.

PMID- 14671382
TI  - A comparison of the ring conformational properties of two derivatives prepared
      from the same diene diacetate precursor.
AB  - Results of single-crystal X-ray experiments performed for the title compounds,
      (1S,2R,3S,4R,5R)-4-benzyloxy-2-[1-(benzyloxy)allyl]-5-hydroxymethyl-2,3,4,5
      tetrahydrofuran-3-ol, C(22)H(26)O(5), (I), and (3R,5S,6S,7S,8S)-3,6
      bis(benzyloxy)-5-iodomethyl-2,3,4,5-tetrahydrofuro[3,2-b]furan-2-one,
      C(21)H(21)IO(5), (II), demonstrate that the tetrahydrofuran ring that is common
      to both structures adopts a different conformation in each molecule. Structural
      analyses of (I) and (II), which were prepared from the same precursor, indicate
      that their different conformations are caused by hydrogen-bonding interactions in
      the case of (I) and the presence of a fused bicyclic ring system in the case of
      (II). Density functional theory calculations on simplified analogs of (I) and
      (II) are also presented.

PMID- 14671383
TI  - Two azasteroidal [3,2-c]pyrazole derivatives: 2'-(p-fluorophenyl)-4
      azapyrazolo[4',3':2,3]-5alpha-androstan-17beta-yl acetate and 2'-(p-fluorophenyl)
      4-azapyrazolo[4',3':2,3]-5alpha-androstan-17beta-ol.
AB  - In both the title aza-steroids, 2'-(p-fluorophenyl)-4-azapyrazolo[4',3':2,3]
      5alpha-androstan-17beta-yl acetate, C(27)H(34)FN(3)O(2), (I), and 2'-(p
      fluorophenyl)-4-azapyrazolo[4',3':2,3]-5alpha-androstan-17beta-ol,
      C(25)H(32)FN(3)O, (II), the tetrahydropyridine ring adopts a half-chair
      conformation and is considerably strained as a consequence of the presence of the
      fused planar pyrazole ring. In both compounds, both cyclohexane rings have chair
      conformations, while the cyclopentane ring has an envelope conformation. All the
      rings of the steroid nucleus are trans fused. In (I), intermolecular N-H.O, C
      H.F, C-H.O and C-H.N interactions are observed in the solid state, while
      intermolecular N-H.O and O-H.N hydrogen bonds are observed in (II).

PMID- 14671384
TI  - Dinicotinamidium squarate.
AB  - The crystal structure determination of the dinicotinamidium squarate salt,
      2C(6)H(7)N(2)O(+).C(4)O(4)(2-), is reported, with the squarate dianion residing
      on an inversion centre and the unique cation in a general position. Salt
      formation occurs by donation of two H atoms from squaric acid to the nicotinamide
      base. The crystal packing is derived from three types of hydrogen bonding. The
      primary hydrogen bond involves a squarate anion O atom and an H atom of the
      protonated pyridine group of the nicotinamide, with an N.O distance of 2.5760
      (13) A. The second hydrogen bond involves a second anion O atom and an amide H
      atom, with an N.O distance of 2.8374 (14) A. Thirdly, an intermolecular
      interaction between two coplanar nicotinamide moieties occurs between an amide O
      atom and a symmetry-related amide H atom, with an N1.O3 distance of 2.8911 (15)
      A. These hydrogen bonds are also responsible for the planarity of the
      nicotinamide moiety in the salt.

PMID- 14671385
TI  - Water polymers in L-alanyl-L-methionine hemihydrate.
AB  - The side chains of L-alanyl-L-methionine hemihydrate,
      C(8)H(16)N(2)O(3)S.0.5H(2)O, form hydrophobic columns within a three-dimensional
      hydrogen-bond network that includes extended polymers of cocrystallized water
      molecules and C(alpha)-H.S interactions.

PMID- 14671386
TI  - Sequelae of syndrome X in children born small for gestational age.
AB  - OBJECTIVE: Low birth weight is associated with the presence of syndrome X in
      adults. We studied the components of this syndrome in prepubertal children born
      SGA (small for gestational age) and children born AGA (appropriate for
      gestational age). METHODS: Twenty-nine SGA children, age (mean +/- SD) 9.1 +/-
      1.1 years and 24 AGA children, age 9.0 +/- 1.1 years were studied. Fasting serum
      lipid concentrations were determined. A hyperinsulinemic euglycemic clamp was
      performed to measure insulin sensitivity. Ambulatory monitoring was performed to
      obtain 24-hour recordings of blood pressure. RESULTS: Prepubertal SGA children
      are less insulin sensitive and have a higher nighttime systolic blood pressure
      (SBP) after correction for BMI than children born AGA. No differences were found
      in lipid concentrations between the 2 groups. CONCLUSIONS: Not all components of
      syndrome X can yet be found in 9-year-old children born SGA; follow-up of this
      cohort is required.

PMID- 14671387
TI  - Increased MIB-1/Ki-67 labeling index as a predictor of an aggressive course in a
      case of prolactinoma.
AB  - Secondary resistance to dopamine agonists is a rare phenomenon in patients with a
      prolactinoma. We describe a 55-year-old male with a macroprolactinoma initially
      responding favorably to bromocriptine treatment with normalization of prolactin
      levels and tumor shrinkage. Two years later, he developed resistance to
      bromocriptine treatment and subsequently to cabergoline. The aggressive course of
      the disease necessitated three surgical interventions. Staining of the pituitary
      tissue revealed a very high MIB/Ki-67 labeling index that increased further in
      specimens derived from repeated surgery. This case demonstrates that high and
      increasing levels of the MIB/Ki-67 labeling index may indicate an aggressive
      course associated with secondary dopamine resistance.

PMID- 14671388
TI  - Biology and clinical application of neural stem cells.
AB  - Neural stem cells, which exist in various regions of the CNS throughout the
      mammalian lifespan, can be expanded and induced to differentiate into neurons and
      glia in vitro and in vivo. Because of these characteristics, there has been
      increasing interest in the identification and characterization of neural stem
      cells and neural progenitor cells both for basic developmental biology studies
      and for therapeutic applications to the damaged brain. Transplantation of neural
      stem cells or their derivatives into a host brain and the proliferation and
      differentiation of endogenous stem cells by pharmacological manipulations are
      potential treatments for many neurodegenerative diseases and brain injuries, such
      as Parkinson's disease, brain ischemia and spinal cord injury. Continued progress
      in neural stem cell research is providing a new future for brain repair.

PMID- 14671389
TI  - Stem cells in diabetes: what has been achieved.
AB  - Beta-cell replacement therapy via islet transplantation has received renewed
      interest due to the recent improved success. In order to make such a therapy
      available to more than a few of the thousands of patients with diabetes, new
      sources of insulin-producing cells must be readily available. The most promising
      sources are stem cells, with efforts of deriving new beta-cells from both
      embryonic and adult stem cells. Several groups have reported generating insulin
      producing cells from mouse embryonic stem cells. The strategies in the first two
      acclaimed reports were very different. One strategy, used by Soria's group, is
      gene trapping in which an introduced antibiotic resistance under the control of
      the insulin promoter allowed the selection of insulin-expressing cells that had
      spontaneously differentiated within embryoid bodies. Another strategy, used by
      McKay's group, manipulated culture conditions in a multistep protocol used for
      generating neural cells but with changed final conditions. Since these reports,
      there have been modifications of the protocols in efforts to improve the yields
      and maturity of the resulting cells. While it is unclear if the insulin-producing
      cells in any of these studies are truly mature beta-cells, these studies show the
      clear potential of embryonic stem cells and support optimism that similar results
      will be possible with human embryonic stem cells. We know that new beta-cells are
      generated throughout adult life, but the identity of adult pancreatic stem cells
      has been elusive. The potential for expansion and differentiation of pluripotent
      adult stem cells, whether from bone marrow or as non-pancreas tissue resident SP
      cells, is being explored but has not yet yielded insulin-producing tissue. In
      contrast, insulin-producing cells have been generated in vitro from adult
      pancreatic tissues. We have been examining the hypothesis that the functional
      source for new beta-cells in the adult pancreas are mature duct epithelial cells
      that have regressed or lost their mature phenotype after replication. Others have
      isolated putative stem cells from islets and ducts. For adult cells the issue of
      expansion as well as of differentiation is a question. The field of generating
      new beta-cells from stem cells, either embryonic or adult, is still in its
      infancy. Each new report has been met with a mixture of excitement and
      skepticism. With continued efforts and rigorous assessments, hopefully the
      potential of generating enough new beta-cells from stem cells will be realized.

PMID- 14671390
TI  - Potential of human embryonic stem cells in regenerative medicine.
AB  - Stem cells can give rise to more stem cells or differentiate into more
      specialized cells. In the last 5 years not only have researchers succeeded in
      isolating human embryonic stem (hES) cell lines but also in identifying adult
      stem cells with possible pluripotent differentiation capacity. The shortage of
      donor organs or tissues for regenerative medicine has further stimulated research
      into the capacity of stem cells to differentiate into different cells and their
      use in replacement therapy in diseases such as Parkinson's, diabetes, rheumatoid
      arthritis and myocardial infarction. Current problems and recent progress with
      respect to hES cells and their potential use for clinical applications will be
      discussed. The potential of adult stem cells for differentiation and tissue
      repair is reviewed elsewhere.

PMID- 14671391
TI  - The neurobiology of female puberty.
AB  - In this review, studies are described indicating that the increase in pulsatile
      release of gonadotropin releasing hormone that signals the initiation of puberty
      requires both changes in transsynaptic communication and the activation of glia
      to-neuron signaling pathways. The major players in the transsynaptic control of
      puberty are neurons that utilize excitatory and inhibitory amino acids as
      transmitters. Glial cells employ a combination of trophic factors and small cell
      cell signaling molecules to regulate neuronal function and thus promote sexual
      development. A neuron-to-glia signaling pathway mediated by excitatory amino
      acids serves to coordinate the simultaneous activation of transsynaptic and glia
      to-neuron communication required for the advent of sexual maturity.

PMID- 14671393
TI  - Early puberty: what is normal and when is treatment indicated?
AB  - Girls and boys who enter puberty before 8 and 9 years of age, respectively
      (corresponding to about -3 SDS), are arbitrarily considered to need referral for
      endocrine investigation. A recent report from the Lawson Wilkins Pediatric
      Endocrine Society suggested that the limit for investigation of girls and boys
      should be lowered to 7 and 8 years, respectively. For African-American girls, 6
      years is the suggested age. This recommendation has been criticized. Although
      short stature is a common end result of precocious puberty, short- and long-term
      psychological symptoms may be more important, since several studies have
      indicated psychopathology in this patient group. Whether this can be prevented by
      gonadotropin releasing hormone agonist treatment remains to be shown. This review
      will highlight the psychological aspects of early puberty. In short, aspects
      other than height should also be evaluated when considering treatment of the
      early maturing child.

PMID- 14671392
TI  - Mutations affecting gonadotropin secretion and action.
AB  - A number of mutations are known to disturb the development and function of the
      hypothalamic-pituitary-gonadal axis. They affect hypothalamic-pituitary-gonadal
      function at multiple levels, from the migration of gonadotropin releasing hormone
      neurons to the hypothalamus right through to gonadotropin action in the ovary and
      testis. Most of the mutations are inactivating, causing various forms of
      hypogonadism. Exceptions are the activating mutations of the luteinizing hormone
      receptor, causing male-limited gonadotropin-independent precocious puberty. The
      human mutations and genetically modified animal models have clarified the
      molecular pathogenesis of hypogonadism and such disorders can now be diagnosed
      using molecular biological techniques, enabling selection of specific treatments
      and appropriate counselling of patients and their families.

PMID- 14671394
TI  - Ascertainment and treatment of delayed puberty.
AB  - The majority of patients with pubertal delay, can be classified as having primary
      pubertal delay (constitutional delay of growth and puberty, CDGP), although any
      child with a chronic disease could present with delayed puberty. In contrast,
      children with hypogonadism, either hyper- or hypogonadotropic, exhibit a total
      absence of pubertal development. Hence, early evaluation of these patients should
      be performed. Delay of puberty leads to psychological problems, secondary to
      short stature and/or delay in the acquisition of secondary sex characteristics
      and the reduction of bone mass. Although the final height in patients with CDGP
      is usually normal, some of these patients do not reach the third percentile or
      remain in the lowest part of the growth chart according to familial height. The
      most common reason for treating CDGP patients, usually with sex steroids, is for
      psychological difficulties and for loss of bone mineralization. Treatment must be
      individualized. Therapeutic options and new drugs will be discussed. Appropriate
      treatment and adequate nutritional intake are indicated in patients with delayed
      puberty due to chronic illness. In patients with hypo- or hypergonadotropic
      hypogonadism, puberty must be induced or completed. Different treatments (GnRH
      analogues, gonadotropins and sex steroids), and the main objectives are
      discussed.

PMID- 14671395
TI  - Testicular dysgenesis syndrome.
AB  - In the Western world fertility rates are low and infertility is a major health
      problem. Unofficial statistics from Denmark reveal that about 6% of all Danish
      children are now born after assisted reproduction techniques, including in vitro
      fertilization, intracytoplasmic sperm injection, donor insemination or homologous
      insemination. However, there are no retrospective data on trends in fecundity
      (ability to conceive). We, and others, have focused on some aspects of adverse
      trends in male reproductive health such as the rising incidence of testicular
      cancer, low and probably declining semen quality, high and possibly increasing
      frequencies of undescended testes and hypospadias. Due to medical specialization
      and the different ages at presentation of symptoms, reproductive problems used to
      be analysed separately by various professional groups, for instance paediatric
      endocrinologists, urologists, andrologists or oncologists. There is evidence that
      poor semen quality, testicular cancer, undescended testes and hypospadias are
      symptoms of one underlying entity, testicular dysgenesis syndrome (TDS), which
      may be increasingly common due to adverse environmental influences. Experimental
      and epidemiological studies suggest that TDS is the result of disruption of
      embryonal programming and gonadal development during fetal life. An endocrine
      disrupter hypothesis to explain the adverse trends has been proposed. It is
      recommended that future epidemiological studies on trends in male reproductive
      health should not focus on one symptom alone, but be more comprehensive and take
      all aspects of TDS into account.

PMID- 14671396
TI  - Breast cancer and the environment.
AB  - The most recent estimate of the overall worldwide burden of cancer is that in the
      year 2000 more than 10 million new cancer cases occurred and approximately 6
      million cancer deaths. Breast cancer accounts for about 1 in 10 cancers and is
      the most frequent cancer affecting women. Since 10% of all cancers in the world
      are breast cancer (only affecting half of the population as breast cancer almost
      exclusively concerns only women), it is being considered an epidemic. In terms of
      the absolute number of incident cases, breast cancer now ranks first not only in
      the industrialized world but also in the developing world. The worldwide
      mortality figure for the year 2000 was 370,000. However, there are marked
      geographical differences, with Africa and Asia currently having incidence rates
      some 10 times lower than those of North America and northern Europe. Studies of
      migrant populations have long indicated that the genetic background only plays a
      tiny, if any, role in these differences. Over time, clear increases have been
      seen in the global number of cases: from 572,000 in 1980 to 1,050,000 in 2000.
      This corresponds not only to a modest increase in incidence rates in countries
      with a long history of frequent breast cancer but also to marked increases in
      countries with previously low rates. The reasons for these increases are
      currently unexplained and a possible hypothesis relates to environmental factors.
      By contrast, in a number of countries in the western world mortality rates are
      stable, and, in the USA and the United Kingdom, even decreasing slightly. The
      aetiology of breast cancer has been the subject of hundreds of studies since the
      pioneering investigation of Lane Claypon in 1926. Risk factors belong to
      different domains: reproductive life, hormonal factors, diet, genetics (BRCA1,
      BRCA2) and exposure to radiation and selected chemicals. Yet, much breast cancer
      remains unexplained and new aetiological links must be sought such as
      occupational factors and exposure to pesticides and other endocrine disrupters. A
      recent international summit on breast cancer and the environment outlined the
      need for more research to be conducted into the effects of exposure in the
      vicinity of nuclear power plants or chemical landfill sites and, more generally,
      into contaminants in food, air, water and soil. This is particularly relevant in
      some parts of the world such as Africa.

PMID- 14671397
TI  - Peroxisome proliferator-activated receptor-gamma and insulin action: insights
      from human genetics.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma), an orphan nuclear
      receptor, mediates adipocyte differentiation and is the cellular target for the
      thiazolidinedione group of insulin-sensitizing antidiabetic agents. We screened
      this receptor gene in a cohort of subjects with severe insulin resistance and
      have identified heterozygous missense mutations in several individuals from three
      families. Functional studies indicate that the receptor mutants are
      transcriptionally impaired and inhibit wild type PPARgamma action in a dominant
      negative manner. The clinical phenotype of patients includes partial
      lipodystrophy, early-onset hypertension, dyslipidaemia and hepatic steatosis.
      Factors which contribute to the severe insulin resistance in affected individuals
      include diminished body fat mass, impaired lipid flux in adipose tissue and
      reduced circulating levels of adiponectin. In a large kindred of five individuals
      with severe insulin resistance, we have identified frameshift/premature stop
      mutations in PPARGAMMA; and the muscle-specific regulatory subunit of protein
      phosphatase 1 (PPP1R3A). The frameshift PPARgamma mutant exhibits complete loss
      of function with no dominant-negative activity; the PPP1R3A truncation mutant is
      mislocalized intracellularly. Individuals harbouring either gene defect alone
      have normal circulating insulin levels, but a combination of both genetic
      abnormalities co-segregates with severe insulin resistance.

PMID- 14671398
TI  - Importance of adipocytokines in obesity-related diseases.
AB  - To elucidate the biological characteristics of adipose tissue, we analyzed the
      gene expression profile of visceral and subcutaneous fat. Unexpectedly, adipose
      tissue, especially visceral fat, expressed a variety of genes for secretory
      proteins. About 30% of the genes expressed in visceral adipose tissue encoded
      secretory proteins and most were biologically active molecules, which we called
      adipocytokines. We found plasminogen activator inhibitor type 1 and heparin
      binding EGF-like growth factor. Production of these atherogenic adipocytokines
      was shown to increase with the accumulation of visceral fat, which may be one of
      the mechanisms of vascular disease in visceral obesity. We found a unique and
      novel collagen-like protein, adiponectin, encoded by the most abundantly
      expressed gene in adipose tissue, termed APM1 (adipose most abundant gene
      transcript-1). Plasma levels of adiponectin ranged from 0.3 to approximately 3
      mg/dl but were decreased in patients with visceral obesity, type 2 diabetes and
      coronary artery disease (CAD). Screening for mutations in the adiponectin gene
      revealed that patients carrying a missense mutation showed markedly decreased
      plasma levels of adiponectin and had CAD. These data suggest that
      hypoadiponectinemia may be considered an important risk factor for CAD. Cell
      biology studies revealed that adiponectin has a potent inhibitory effect on the
      expression of adhesion molecules in endothelial cells and an inhibitory effect on
      the expression in macrophages. In order to confirm these antidiabetic and
      antiatherogenic functions of adiponectin, we developed adiponectin knockout mice.
      Adiponectin knockout mice showed severe insulin resistance and impaired glucose
      metabolism when fed a high-fat, high-sucrose diet. Knockout mice also developed
      intimal thickening in response to endothelial injury.

PMID- 14671399
TI  - Molecular basis for the treatment of achondroplasia.
AB  - Achondroplasia (ACH), the most common form of short-limbed dwarfism, and its
      related disorders are caused by constitutively activated point-mutated fibroblast
      growth factor receptor 3 (FGFR3). Recent studies have provided a large body of
      evidence to prove chondrocyte proliferation and differentiation in these
      disorders. However, little is known about the possible effects of the FGFR3
      mutants on apoptosis of chondrocytes. In the present study, we analyzed apoptosis
      using a chondrogenic cell line, ATDC5, expressing the FGFR3 mutants causing ACH
      and thanatophoric dysplasia, which is a more severe neonatal lethal form
      comprising type I and type II. We found that the introduction of these mutated
      FGFR3s into ATDC5 cells decreased mRNA expression of parathyroid hormone-related
      peptide (PTHrP) and induced apoptosis. Importantly, replacement of PTHrP
      prevented the apoptotic changes in ATDC5 cells expressing ACH mutant. Insulin
      like growth factor (IGF)-I, which is an important mediator of growth hormone
      (GH), also reduced apoptosis in ATDC5 cells expressing ACH mutant. IGF-I
      prevented apoptosis through the phosphatidylinositol 3-kinase and mitogen
      activated protein kinase pathways, indicating the mechanisms by which GH
      treatment improves disturbed bone growth in ACH.

PMID- 14671400
TI  - Skeletal dysplasia, growth hormone treatment and body proportion: comparison with
      other syndromic and non-syndromic short children.
AB  - Skeletal dysplasias comprise a diverse group of conditions that usually
      compromise both linear growth and body proportions. It is of theoretical interest
      to evaluate the effect of GH treatment on linear growth, body proportion and
      final height in the different skeletal dysplasias. Reported experience of GH
      treatment in short children with skeletal dysplasia is sparse and often limited
      to short treatment periods and knowledge of its effects on final height and body
      proportion is generally lacking. Formal studies are almost all confined to
      achondroplasia as the most common entity. First-year response is typically a 2-3
      cm increase in growth velocity in prepubertal children, or a gain of about 0.5
      SDS or less in relative height from a baseline level of -4 to -5 SDS. GH
      treatment for up to 5 years in achondroplasia can produce a total height gain of
      about 1 SDS. Apart from achondroplasia, treatment of hypochondroplasia and
      dyschondrosteosis with GH has been reported in a small number of patients. Long
      term data are, however, lacking. Of theoretical interest is that in many
      syndromic or non-syndromic short-statured children body proportion, i.e. trunk to
      leg length ratio, does not seem to be dependent on the degree of GH sufficiency
      and does not seem to be changed by GH treatment. GH treatment, at least in the
      prepubertal period, does seem to influence degree of disproportion.

PMID- 14671401
TI  - Normal acquisition and loss of bone mass.
AB  - The natural patterns of bone mass accumulation and loss with age represent the
      templates of individual life cycle periods that are distinguished by marked,
      physiologically and genetically identifiable, changes in bone mass. During the
      third trimester of pregnancy, maternal calcium absorption increases and the fetus
      accumulates about two-thirds of the total bone mass of the term infant. In early
      infancy, human milk calcium is derived primarily from maternal bone stores, which
      incur substantial bone losses that are quickly replenished during and after
      weaning. At puberty, a marked increase in bone mass occurs in conjunction with
      the initial physical and hormonal changes that characterize this stage. Calcium
      absorption and bone calcium deposition rates peak in females shortly before
      menarche. At that time, the bone calcium deposition rate is approximately five
      times that of adulthood. Skeletal bone mass reaches over 90% of its maximum by
      age 18 (earlier in females) but does not peak until age 25-30. At some point in
      mid-life, women experience perimenopause, the 3- to 5-year period prior to
      menopause during which estrogen levels begin to drop and there are marked
      increases in bone resorption and loss. Throughout adulthood, calcium absorption
      efficiency from the diet gradually declines.

PMID- 14671402
TI  - Glucocorticoid-induced osteoporosis.
AB  - Osteoporosis is a common and serious complication of glucocorticoid therapy,
      resulting in increased risk of fragility fractures. Recent studies indicate that
      fracture risk is increased even at low doses of glucocorticoids and that this
      increased risk is seen soon after the commencement of glucocorticoid therapy.
      Both increased bone resorption and reduced bone formation contribute to bone
      loss, which affects cortical and cancellous sites. A number of interventions have
      been shown to prevent glucocorticoid-induced bone loss, although the strongest
      evidence exists for the bisphosphonates etidronate, alendronate and risedronate.
      Primary prevention of bone loss should be considered in all high-risk individuals
      taking oral glucocorticoids for 3 months or more, for example those aged 65 years
      or over or those with a previous fragility fracture. In other glucocorticoid
      treated individuals, the decision to treat should be based on bone densitometry.

PMID- 14671403
TI  - Growth hormone and bone health.
AB  - Growth hormone (GH) and insulin-like growth factor-I have major effects on growth
      plate chondrocytes and all bone cells. Untreated childhood-onset GH deficiency
      (GHD) markedly impairs linear growth as well as three-dimensional bone size.
      Adult peak bone mass is therefore about 50% that of adults with normal height.
      This is mainly an effect on bone volume, whereas true bone mineral density (BMD;
      g/cm(3)) is virtually normal, as demonstrated in a large cohort of untreated
      Russian adults with childhood-onset GHD. The prevalence of fractures in these
      untreated childhood-onset GHD adults was, however, markedly and significantly
      increased in comparison with normal Russian adults. This clearly indicates that
      bone mass and bone size matter more than true bone density. Adequate treatment
      with GH can largely correct bone size and in several studies also bone mass, but
      it usually requires more than 5 years of continuous treatment. Adult-onset GHD
      decreases bone turnover and results in a mild deficit, generally between -0.5 and
      -1.0 z-score, in bone mineral content and BMD of the lumbar spine, radius and
      femoral neck. Cross-sectional surveys and the KIMS data suggest an increased
      incidence of fractures. GH replacement therapy increases bone turnover. The three
      controlled studies with follow-up periods of 18 and 24 months demonstrated a
      modest increase in BMD of the lumbar spine and femoral neck in male adults with
      adult-onset GHD, whereas no significant changes in BMD were observed in women.
      GHD, whether childhood- or adult-onset, impairs bone mass and strength.
      Appropriate substitution therapy can largely correct these deficiencies if given
      over a prolonged period. GH therapy for other bone disorders not associated with
      primary GHD needs further study but may well be beneficial because of its
      positive effects on the bone remodelling cycle.

PMID- 14671404
TI  - Genetic basis for resistance to parathyroid hormone.
AB  - Pseudohypoparathyroidism (PHP) is associated with biochemical hypoparathyroidism
      (i.e. hypocalcemia and hyperphosphatemia) due to parathyroid hormone (PTH)
      resistance rather than to PTH deficiency. Patients with PHP type 1a have a
      generalized form of hormone resistance plus a constellation of developmental
      defects termed Albright hereditary osteodystrophy (AHO). Within PHP type 1a
      families some individuals will show AHO but have normal hormone responsiveness, a
      variant phenotype termed pseudo-PHP. By contrast, patients with PHP type 1b
      manifest only PTH resistance and lack features of AHO. These various forms of PHP
      are due to defects in the GNAS1 gene that lead to decreased expression or
      activity of the alpha-subunit of the stimulatory G protein (G(s)alpha). Tissue
      specific genomic imprinting of GNAS1 accounts for the variable phenotypes of
      patients with GNAS1 defects.

PMID- 14671405
TI  - Identification of novel genes involved in congenital hypothyroidism using serial
      analysis of gene expression.
AB  - Part of the molecular basis of congenital hypothyroidism (CH) has been elucidated
      by the identification of molecular defects in pituitary- and thyroid-specific
      genes in patients with various subtypes of hypothyroidism. So far identified
      genetic defects only explain a small proportion of cases of hypothyroidism. Thus
      novel research strategies are required to isolate more tissue-specific genes
      involved in the pathogenesis of CH at present considered 'idiopathic' from a
      molecular perspective. We applied serial analysis of gene expression to human
      thyroid tissue and developed a computational substraction method to identify
      tissue-specific genes. The result has been the identification of three genes
      preferentially expressed in the thyroid gland. The first one encodes part of the
      thyroid oxidase (THOX2) system. We linked mutations in the THOX2 gene with
      idiopathic cases of transient and permanent CH. The second transcript identified,
      DEHAL1, encodes the protein responsible for the recycling of iodine in the
      thyroid gland and represents the candidate gene for a specific subtype of CH. The
      third one encodes NM41, a protein currently under investigation which shows
      features characteristic of the CYSTINE-KNOT family of proteins, typically
      involved in early development.

PMID- 14671406
TI  - History and future of growth hormone research.
AB  - The understanding of the mechanisms of growth hormone (GH) action has seen great
      accomplishments over the last two decades. These achievements include the cloning
      of a variety of GH and GH receptor (GHR) genes and cDNAs; solving of the three
      dimensional structure of GH and the GH/GHR complex, and the discovery of GH
      antagonists. These GH antagonists have resulted in a new class of drugs with
      important clinical implications. Animal models in which the GH/insulin-like
      growth factor (IGF)-I axis has been perturbed also have resulted in many novel
      findings. We have now entered the era of genomics and proteomics. Genes and
      proteins that are up- or downregulated as a function of GH action (or lack
      thereof) will add to the repertoire of knowledge that will lead to a better
      understanding of the molecular basis of GH action.

PMID- 14671407
TI  - Final height data, body composition and glucose metabolism in growth hormone
      treated short children born small for gestational age.
AB  - Low birth weight has been associated with impaired insulin sensitivity, type 2
      diabetes mellitus, hypertension and cardiovascular disease in later life. GH
      therapy is known to increase fasting and postprandial insulin levels. For this
      reason concern has been expressed regarding the possible detrimental effects of
      GH therapy in children born small for gestational age (SGA). To assess the
      effects of GH therapy on body composition, carbohydrate metabolism and final
      height in short SGA children, 165 prepubertal short children born SGA were
      enrolled in either a multicentre, double-blind, randomized, dose-response GH
      trial (n = 75) or in a GH controlled trial (n = 90). The inclusion criteria were:
      (1) birth length standard deviation score (SDS) below -2; (2) age 3-8 years; (3)
      height SDS below -2. The children's mean (SD) age was 7.3 (2.1) years (GH dose
      response trial) and 6.0 (1.5) years (GH controlled trial), birth length SDS was 
      3.6 and height SDS was -3.0 (0.7). In the GH dose-response trial, children were
      randomly assigned to either 1 mg GH/m(2) per day (group A, n = 41) or 2 mg
      GH/m(2) per day (group B, n = 38) ( approximately 0.033 or 0.067 mg/kg per day,
      respectively). In the GH controlled trial, children were randomly assigned to 1
      mg GH/m(2) per day (n = 60) or served as controls (n = 30). Subjects underwent
      standard oral glucose tolerance tests and measurement of body mass index,
      systolic and diastolic blood pressure and serum lipids at baseline and after 1
      and 6 years of GH therapy and again 6 months after discontinuation of GH. Body
      composition was measured by dual energy x-ray absorptiometry at baseline and
      again after 3 years in the GH controlled trial. Mean (SD) final height SDS was
      not significantly different between the two GH dosage groups: -1.2 (0.7) in group
      A and -0.8 (0.7) in group B. At the start of GH therapy, 8% of children had
      impaired glucose tolerance (IGT). Systolic blood pressure was significantly
      higher in comparison with healthy peers. GH therapy induced considerably higher
      fasting and glucose-stimulated insulin levels after 1 and 6 years, regardless of
      GH dosage. After 6 years, 4% of children had IGT. Six months after
      discontinuation of GH, glucose levels remained normal, whereas fasting and
      glucose-stimulated insulin returned to levels comparable to those of healthy
      peers. None of the children developed diabetes. During 6 years of GH therapy both
      systolic and diastolic blood pressure decreased significantly and remained so
      after discontinuation of GH therapy. At baseline all children had reduced bone
      mineral content and lean body mass. Fat mass was not significantly lower than
      normal. Treatment with 1 mg GH/m(2) per day resulted in a significant increase in
      (and normalization of) bone mineral content and lean body mass in comparison with
      untreated short SGA controls. Fat mass decreased during the first year of GH but
      returned to values comparable to those at baseline in the following 2 years of GH
      therapy. We found that long-term, continuous GH therapy in short children born
      SGA leads to a normalization of height during childhood and to a normal final
      height in most children, regardless of GH dosage. Only very short or relatively
      older children may need a dosage of 2 mg GH/m(2) per day. Long-term GH therapy
      had no adverse effects on glucose levels and serum lipids and had a positive
      effect on blood pressure, even with GH dosages of up to 2 mg/m(2) per day.
      However, as has been reported in other patient groups, GH induced higher fasting
      and glucose-stimulated insulin levels, indicating insulin resistance. After
      discontinuation of GH serum insulin levels returned to normal age-reference
      levels. Short SGA children have a reduction in bone mineral content and lean body
      mass when compared with healthy controls, which significantly improved
      (normalized) with GH therapy at a dose of 1 mg/m(2) per day.

PMID- 14671408
TI  - Insulin-like growth factors and their binding proteins in children born small for
      gestational age: implication for growth hormone therapy.
AB  - The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are
      important regulators of growth and metabolism and are the key mediators of the
      actions of growth hormone (GH). Children born small for gestational age (SGA)
      have a host of medical problems including an increased risk of poor growth later
      in life, a tendency to develop metabolic abnormalities and a high incidence of
      learning disabilities. IGFs and related molecules may be linked to all of these
      concerns. Mouse models of IGF-I and IGF-II deficiencies have phenotypes
      reminiscent of human SGA, including slow growth, insulin resistance, and mental
      dysfunction. Humans with IGF-I mutations are born SGA and exhibit very poor
      subsequent growth, metabolic syndrome and mental retardation. Current management
      of children born SGA who present with growth failure during childhood includes
      treatment with GH. SGA children usually have growth factor levels within the
      normal range; however, as a group, they display lower IGFBP-3 levels in relation
      to their IGF-I levels. GH is effective in improving growth in children born SGA,
      but higher doses of GH are required to achieve optimal outcome, suggesting a
      component of GH insensitivity in SGA children. As in other indications for GH, a
      rational monitoring approach (focusing on maintaining IGF levels in the high
      normal range) is prudent.

PMID- 14671409
TI  - Insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3,
      phosphoisoforms of IGFBP-1 and postnatal growth in very-low-birth-weight infants.
AB  - Small preterm infants experience a unique postnatal period characterized by slow
      growth, inadequate nutrition and growth inhibiting treatments. Many have already
      been growth-restricted in utero. Studying this period is important when
      developing growth optimizing strategies for these infants and, in a broader
      context, as a model of extreme conditions that restrict growth. By following
      short-term growth of 48 very-low-birth-weight (VLBW; birth weight <1,500 g)
      infants for 9 postnatal weeks, we found that circulating insulin-like growth
      factor (IGF)-I and IGF binding protein (IGFBP)-3 levels are low and reflect
      rigorously measured (knemometry and weight) concurrent growth velocity. Moreover,
      weight growth velocity is correlated with the ratio of lesser to highly
      phosphorylated IGFBP-1 but not with absolute IGFBP-1 concentrations. Thus, IGF-I,
      IGFBP-3 and the phosphorylation status of IGFBP-1 in circulation are likely to be
      involved in growth regulation during the postnatal period in VLBW infants.

PMID- 14671410
TI  - Serum insulin-like growth factor-I levels and potential risk of type 2 diabetes.
AB  - The effects of circulating insulin-like growth factor (IGF)-I on increasing
      insulin sensitivity are well recognized. IGF-I may have a further important role
      in maintaining beta-cell mass, and lower IGF-I activity could explain links
      between small size at birth and risk of type 2 diabetes in short, obese adults.
      In the representative Avon Longitudinal Study of Pregnancy and Childhood birth
      cohort, whereas insulin sensitivity is related to early postnatal weight gain,
      insulin secretion is related to IGF-I level and statural growth. Adult studies
      suggest that lower IGF-I levels at baseline predict increased risk for developing
      impaired glucose tolerance and type 2 diabetes. A common genetic polymorphism in
      the IGF1 gene could influence size at birth, postnatal growth and type 2 diabetes
      risk, but results of studies have been inconsistent. Extrapolation of these data
      to short children born small for gestational age is complex. Some have evidence
      of IGF-I and insulin resistance, suggesting inherent defects in IGF-I signalling.
      These children have poor growth responses to growth hormone (GH) therapy and
      perhaps the highest type 2 diabetes risk. Where these metabolic abnormalities are
      less severe, responses to GH therapy are good and diabetes risk may then depend
      on other genetic factors, indicated by a family history of diabetes or origin
      from ethnic groups with high diabetes prevalence.

PMID- 14671411
TI  - Intrauterine growth retardation and consequences for endocrine and cardiovascular
      diseases in adult life: does insulin-like growth factor-I play a role?
AB  - Low birth weight has been associated with an increased incidence of ischaemic
      heart disease (IHD) and type 2 diabetes. Endocrine regulation of fetal growth by
      growth hormone (GH) and insulin-like growth factor (IGF)-I is complex. Placental
      GH is detectable in maternal serum from the 8th to the 12th gestational week, and
      rises gradually during pregnancy where it replaces pituitary GH in the maternal
      circulation. The rise in placental GH may explain the pregnancy-induced rise in
      maternal serum IGF-I levels. In the fetal compartment, IGF-I levels increase
      significantly in normally growing fetuses from 18 to 40 weeks of gestation, but
      IGF-I levels are four to five times lower than those in the maternal circulation.
      Thus IGF-I levels in fetal as well as in maternal circulation are thought to
      regulate fetal growth. Circulating levels of IGF-I are thought to be genetically
      controlled and several IGF-I gene polymorphisms have been described. IGF-I gene
      polymorphisms are associated with birth weight in some studies but not in all.
      Likewise, IGF-I gene polymorphisms are associated with serum IGF-I in healthy
      adults in some studies, although some controversy exists. Serum IGF-I decreases
      with increasing age in healthy adults, and this decline could hypothetically be
      responsible for the increased risk of IHD with ageing. A recent nested case
      control study found that adults without IHD, but with low circulating IGF-I
      levels and high IGF binding protein-3 levels, had a significantly increased risk
      of developing IHD during a 15-year follow-up period. In summary, the GH/IGF-I
      axis is involved in the regulation of fetal growth. Furthermore, it has been
      suggested that low IGF-I may increase the risk of IHD in otherwise healthy
      subjects. Hypothetically, intrauterine programming of the GH/IGF axis may
      influence postnatal growth, insulin resistance and consequently the risk of
      cardiovascular disease. Thus IGF-I may serve as a link between fetal growth and
      adult-onset disease.

PMID- 14671412
TI  - Three-dimensional sonographic features of placental abnormalities.
AB  - OBJECTIVE: To describe three-dimensional (3D) sonographic features of placental
      abnormalities in utero. METHODS: A total of 6 cases with placental abnormalities
      (1 chorioangioma, 1 subchorionic hematoma, 2 placental cysts, and 2 subplacental
      fibromas) from 22 to 34 weeks of gestation were studied with transabdominal 3D
      sonography. RESULTS: Placental abnormalities could be easily imaged with both two
      dimensional (2D) and 3D sonography; however, visualization of the continuity and
      curvature of structures was more easily accomplished with 3D sonography. In the
      case with chorioangioma, the thick and rough surface of the tumor was clearly
      depicted. With the use of color Doppler ultrasound, only a case of chorioangioma
      was shown to have abundant blood flow within the tumor. In cases with placental
      cyst and subchorionic hematoma, the wall of the cyst becomes a transparent-like
      structure, so internal textures can be clearly identified. In the case with
      subplacental fibroma, the location in relation to the placenta was clearly
      recognized. CONCLUSION: These results suggest that 3D sonography has the
      potential to be a supplement to 2D sonography and color Doppler ultrasound in
      identifying placental masses and provides a novel means of visualizing placental
      abnormalities in utero.

PMID- 14671413
TI  - Medical fellowship programme within the Gynaecological Cancer Group of the
      European Organisation for Research and Treatment of Cancer.
AB  - In 1962, the European Organisation for Research and Treatment of Cancer (EORTC)
      was founded, and in the course of the years it developed into the leading
      European organisation in cancer research. Currently, the EORTC is organised into
      (Pre-)Clinical Groups and Task Forces consisting of scientists and/or clinicians.
      One of these groups with a specific area of interest in cancer research is the
      Gynaecological Cancer Group (GCG). The EORTC offers fellowship programmes to
      physicians and scientists from all over the world to create a possibility to be
      temporarily linked to an EORTC group or a specific research project. Over the
      past decade, 76 research fellowships have been appointed at the EORTC Data
      Center. This paper shows an overview of the activities of one EORTC/GCG medical
      fellow.

PMID- 14671414
TI  - Organic hydroperoxide-induced chemiluminescence of follicular fluid and blood
      serum samples obtained from women pretreated for in vitro fertilization.
AB  - The organic hydroperoxide-induced chemiluminescence of follicular fluid obtained
      from in vitro fertilized patients and its differently separated fractions were
      evaluated. Peroxidative stress causes a different photo-emission in the samples
      which alludes to some factors playing a role in the maintenance of the pro
      oxidant/antioxidant balance. Interactions between the protein compounds of the
      samples and the organic hydroperoxide associate with formation of excited species
      contributing to the distinctive light emission processes. The technique offers a
      special re-interpretation of the scavenger state relating to the components of
      follicular fluid.

PMID- 14671415
TI  - Electro-acupuncture reverses nerve growth factor abundance in experimental
      polycystic ovaries in the rat.
AB  - Polycystic ovary syndrome (PCOS) remains one of the most common causes of
      anovulation in women of reproductive age. There is some evidence that nerve
      growth factor (NGF) is involved in the pathogenesis of PCOS. Therefore, seeking
      the pathogenesis of PCOS is important for controlling fertility. In traditional
      Oriental Medicine, acupuncture has been used for the function of ovaries. The
      present study was designed to determine whether electro-acupuncture (EA) could
      affect experimentally induced polycystic ovary (PCO) in the rat. The two
      acupoints Sp-6 and E-128 were stimulated to test for efficacy in the protein
      expression of NGF. Polycystic ovaries were induced by a single injection of
      estradiol valerate (4 mg i.m.). During the experimental period of 8 weeks, some
      of the rats were treated with EA twice weekly; this group was compared with a
      vehicle-treated control group and an estradiol-injected group not subjected to
      EA. At day 60, the protein expression of NGF was examined by immunohistochemistry
      in the ovaries, the adrenal glands and some parts of the brain. The estradiol
      treatment induced a clear PCO appearance, and was associated with a robust
      increase in NGF expression in the ovaries, the adrenal glands and the brain. EA
      treatment partly reversed the NGF abundance, particularly in the ovaries, but not
      in the brain. Our data show that EA affects the NGF involvement in ovarian
      dysfunction.

PMID- 14671416
TI  - Divalent cation levels in serum and preovulatory follicular fluid of women
      undergoing in vitro fertilization embryo transfer.
AB  - In this controlled clinical study, we determined the serum and follicular fluid
      concentrations of the biologically active fractions of magnesium (Mg) and calcium
      (Ca) in 39 women undergoing controlled ovarian stimulation (COH) for in vitro
      fertilization (IVF) embryo transfer (ET). Serum levels of ionized Ca (Ca2+) and
      ionized Mg (Mg2+) were measured during day 3 of the IVF cycle, on the day of ovum
      pickup and 12 days following ET. Follicular fluid levels were measured on the day
      of ovum pickup. Serum levels of Mg2+ decreased and Ca2+ levels increased during
      the IVF cycle. Mg levels were significantly higher in follicular fluid than in
      serum. Ca2+ and Mg2+ may play a role in the preovulatory follicle, a possibility
      that warrants further study.

PMID- 14671417
TI  - Endometriotic uterocutaneous fistula after cesarean section. A case report.
AB  - Endometriosis outside the pelvis is rare and most cases occur in surgical scars
      after operations involving the female genital tract. Fistulae involving the
      uterus are also very rare, usually being the result of postpartum and
      postoperative complications. In the present report, a case of a 44-year-old
      patient with an endometriotic uterocutaneous fistula is described. The patient
      presented 6 years after her fourth cesarean section with a painful nodule on the
      cesarean scar, which was bleeding during menstruation. The lesion extended to the
      uterine fundus, connecting the endometrial cavity with the skin. This is merely
      the second case of a uterocutaneous fistula to be reported in the literature and
      the first case developed on grounds of endometriosis.

PMID- 14671418
TI  - Usefulness of preoperative chemoradiation in locally advanced cervical carcinoma.
AB  - This study investigated response rate, toxicity, and influence on intra- and
      postoperative complications of neoadjuvant concurrent chemoradiation in locally
      advanced (Figo IB2-IIIB) cervical carcinomas. Twenty-eight patients (median age
      46.5 years, age range 29-73 years), diagnosed as having squamous cell carcinomas
      (n=21), adenocarcinomas (n=6), and undifferentiated carcinoma (n=1), entered this
      study. The chemoradiation protocol included external radiotherapy to the pelvis
      (39.6 Gy), intra-arterial or intravenous infusion of cisplatin (70 mg/m2 on days
      1 and 22), and 24-hour continuous intravenous infusion of 5-fluorouracil (700
      mg/m2 on days 1-4 and 22-25). Two weeks after the end of chemoradiotherapy, the
      patients underwent restaging followed by suitable operation including pelvic
      lymphadenectomy. The median follow-up period in the surviving patients was 13.1
      months. The response rate for chemoradiation was 93% (26/28). The 2-year disease
      free survival was 85.2%. Grade 3-4 neutropenia was observed in 14 patients (50%),
      4 patients (14%) showed grade 3 anemia, and 5 patients (17.8%) showed grade 3-4
      thrombocytopenia. Nineteen patients (67.8%) could undergo surgery after
      concurrent chemoradiation. Pathological examination revealed a complete response
      (pT0) in 7 patients, and 5 patients showed only microscopic residual disease
      (pTmic). In 4 patients, there were intraoperative complications: vesical lesions
      in 2 (10%) and small intestine lesions in 2 (10%). Neoadjuvant therapy with
      concurrent chemoradiation for locally advanced cervical carcinoma is effective,
      safe, and useful for increasing operability rates as well as decreasing intra-
      and postoperative complications. Therefore, neoadjuvant concurrent chemoradiation
      should be considered for treatment in patients with locally advanced cervical
      carcinomas who could not undergo primary operation.

PMID- 14671419
TI  - A monozygotic conjoined twin pregnancy discordant for laterality of cleft lip.
AB  - Conjoined twins discordant for phenotype of cleft lip are reported. One had right
      sided cleft lip, while the co-twin had left-sided cleft lip. Both twins had a
      normal 46,XY karyotype. Genotyping at 50 polymorphic loci revealed that the twins
      were identical (monozygotic). Our analysis suggests that the laterality of cleft
      lip is more affected by the process of twinning than by genetic factors.

PMID- 14671420
TI  - Lack of association between Leber's hereditary optic neuropathy primary point
      mutations and multiple sclerosis in Iran.
AB  - The hypothesis that mitochondrial genes may implicate susceptibility to multiple
      sclerosis (MS) is supported by an increasing number of case reports on Leber's
      hereditary optic neuropathy (LHON)-associated mitochondrial DNA (mtDNA) point
      mutations in patients with MS. A number of mtDNA mutations with primary
      pathogenic significance for LHON, a maternally inherited disease causing severe
      bilateral visual loss predominantly in young men, have been detected in patients
      with an MS-like phenotype. To evaluate the link between MS and LHON primary point
      mutations, we investigated 31 non-related Iranian clinically definite MS patients
      (23 females and 8 males) with optic nerve involvement, as well as 25 patients (16
      females and 9 males) without involvement of the optic nerve as controls. Three
      patients had severe bilateral visual loss without any recovery. We searched for
      the presence of LHON mitochondrial mutations at nucleotide positions (np) 11,778,
      3,460, and 14,484 by mutation-specific polymerase chain reaction and restriction
      fragment length polymorphism. Our results suggest that there is no association
      between Iranian patients with MS and mtDNA point mutations at np 11,778, 3,460,
      and 14,484.

PMID- 14671421
TI  - Extremely early onset of ranitidine action on human histamine H2 receptors
      expressed in HEK293 cells.
AB  - BACKGROUND/AIMS: Histamine H2 receptor antagonists are considered to exert their
      effects on gastric acid secretion more rapidly than proton pump antagonists.
      However, there are no reports concerning the direct interaction of a histamine H2
      receptor antagonist with the human H2 receptor in terms of onset of action. This
      study aims to characterize how rapidly famotidine and ranitidine, the most widely
      used histamine H2 receptor antagonists, interact with the human histamine H2
      receptor. METHODS: HEK293 cell lines, stably expressing human histamine H2
      receptors, were obtained. The dose- and time-dependent effects of famotidine and
      ranitidine on [3H]-tiotidine binding and histamine-stimulated cAMP production
      were analyzed. RESULTS: Ranitidine inhibited both [3H]-tiotidine binding and
      histamine-stimulated cAMP production more promptly than did famotidine.
      Inhibition of histamine-stimulated cAMP production by Cmax doses of famotidine
      (20 mg p.o.) and ranitidine (150 mg p.o.) peaked by 15 and 2 min, respectively.
      [3H]-tiotidine binding was not saturated by 60 min at the famotidine Cmax, while
      the ranitidine Cmax had produced saturation by 15 min. CONCLUSION: Ranitidine
      inhibits the human histamine H2 receptor very rapidly.

PMID- 14671422
TI  - Validation of a reliable instrument (QUOTE-IBD) for assessing the quality of
      health care in Greek patients with inflammatory bowel disease.
AB  - Given the early onset, the chronic and recurrent nature of their disease and
      their normal life expectancy, patients with inflammatory bowel disease (IBD) may
      need considerable health care. The purpose of this study is to validate the Greek
      translation of the QUOTE-IBD questionnaire (GR-QUOTE-IBD). For that purpose we
      assessed its construct validity, and reliability. Fifty patients (33 ulcerative
      colitis, 17 Crohn's disease) completed the GR-QUOTE-IBD and visual-analogue
      scales (VAS) for the patients' evaluation of the quality of separate care
      dimensions, and of the total care. A subgroup of 33 patients (64%) completed the
      GR-QUOTE-IBD for a second time. Quality of life was assessed by the short version
      of the IBDQ. Clinical activity was assessed by Harvey-Bradshaw index and Colitis
      Activity Index. Correlations among all care dimensions and VAS were positive and
      highly significant (p<0.001). The total care and all eight dimensional care
      scores (quality impact and importance) had no significant differences between the
      baseline and the follow-up visit. Similarly, the correlation coefficients between
      the scores of the two occasions were all positive (close to one) and highly
      significant (p<0.001). The GR-QUOTE-IBD proved to be a valid and reliable
      instrument, applicable in international clinical studies.

PMID- 14671423
TI  - Los function and obesity: the impact of untreated obesity, weight loss, and
      chronic gastric balloon distension.
AB  - BACKGROUND/AIMS: In obesity, many gastro-oesophageal reflux promoting factors are
      present. Weight reduction is advised to symptomatic overweight subjects. The aim
      of the present study was to investigate the influences of untreated obesity,
      weight loss, and chronic gastric balloon distension on the lower oesophageal
      sphincter (LOS) function. METHODS: Patients entering a randomized, double-blind,
      sham-controlled study of balloon treatment, consisting of 4 months of either sham
      balloon or balloon treatment followed by 4 months of balloon treatment. Manometry
      and 24-hour pH measurements were performed at the start of the study and after 13
      and 26 weeks. RESULTS: Before treatment, LOS dysfunction was present in 7 of 32
      patients (21.9%). Increased upright and supine reflux was present in 8 patients
      (25%). Sham treatment resulted in a weight loss of 9.7% with improved LOS
      function (a significant 0.6-cm increase in LOS length and a non-significant 2.6
      mm Hg higher LOS pressure) and in a significantly decreased upright reflux (acid
      reflux time decreasing from 8.0 to 5.5% and number of meal-related and
      postprandial reflux episodes decreasing from 49 to 32). These improved values
      deteriorated after 4 months of balloon placement, with significantly increasing
      total, upright, and supine reflux to 7.5, 7.6, and 6.7% of the time,
      respectively, with oesophageal lesions after an overall 17.8% weight loss. Four
      months of balloon treatment induced a similar weight loss (9.9%) with
      significantly increased supine reflux from 1.6 to 6.7% of the time. After a
      second 4-month balloon period and an overall 13.8% weight loss, LOS and reflux
      values returned towards baseline values. A comparison of both groups demonstrated
      the adverse effects of balloon positioning after a period of substantial sham
      induced weight loss. CONCLUSIONS: Impaired LOS function and increased gastro
      oesophageal reflux were observed in one quarter of the untreated obese subjects.
      Weight loss ameliorated manometry and pH values, but subsequent balloon
      positioning tended to counteract these beneficial changes. In patients on balloon
      treatment from the start, adverse effects seemed to wear off with prolonged
      treatment.

PMID- 14671424
TI  - Serum progastrin and its products, gastric acid secretion and serum pepsinogen I
      in gastric cancer.
AB  - BACKGROUND: Numerous studies have shown an association between Helicobacter
      pylori (Hp) infection and gastric cancer (GC). STUDY: This study was designed to
      determine the role of cytotoxin-associated gene A (CagA)-positive Hp infection,
      serum amidated gastrins and their precursor, progastrin, gastric acidity and
      serum pepsinogen I (PG-I) levels in gastric cancerogenesis in 74 cancer patients
      and in 77 age- and gender-matched controls. Serum IgG antibodies to Hp and CagA
      and levels of IL-8 and PG-I were measured by ELISA, while progastrin and amidated
      gastrin by specific radioimmunoassay. RESULTS: The overall Hp and CagA
      seropositivity in GC patients were significantly higher (82 and 60%) than in
      matched controls (61 and 27%, respectively). Progastrin and amidated gastrin
      levels over their cutoff points (122 and 32 pM, respectively) were found in a
      significantly larger number of GC (59.4 and 44.5%) than in controls (9.0 and
      16.8%, respectively). Histologically, all these GCs with increased serum
      progastrin and amidated gastrins were of intestinal type and showed CagA and Hp
      seropositivity. Serum IL-8 and gastric pH, above their cutoff points (pH >4.5),
      and serum PG-I level below its cutoff point (44.2 microg/l) were observed in a
      significantly higher number of GC patients as compared to controls. CONCLUSIONS:
      (1) GC patients have higher Hp and CagA seroprevalence than matched controls,
      confirming that CagA-positive Hp infection is associated with higher risk of GC;
      (2) serum levels of amidated gastrins and their precursor, progastrin, as well as
      IL-8 are significantly higher, while serum PG-I levels are reduced in intestinal
      type GC compared to controls, and (3) determination of high serum progastrin,
      amidated gastrins and IL-8 combined with low serum PG-I may be useful biomarkers
      of GC.

PMID- 14671425
TI  - Abnormal colonic propagated activity in patients with slow transit constipation
      and constipation-predominant irritable bowel syndrome.
AB  - BACKGROUND: The pathophysiological basis of constipation is still unclear, and
      the role of colonic dysfunction is debated, especially in irritable bowel
      syndrome. Objective data are quite scarce, especially concerning colonic
      propulsive activity. AIMS: To evaluate high- and low-amplitude colonic propulsive
      activity in constipated patients (slow-transit type and irritable bowel syndrome)
      in comparison with normal controls. PATIENTS AND METHODS: Forty-five constipated
      patients (35 with slow-transit constipation and 10 with constipation-predominant
      irritable bowel syndrome) were recruited, and their data compared to those of 18
      healthy subjects. Twenty-four-hour colonic manometric recordings were obtained in
      the three groups of subjects, and data concerning high- and low-amplitude colonic
      propulsive activity were then compared. RESULTS: High-amplitude propagated
      contractions were significantly (p < 0.05) decreased in patients with slow
      transit constipation and constipation-predominant irritable bowel syndrome with
      respect to controls (1.5 +/- 0.4, 3.7 +/- 2, and 6 +/- 1 events/subject/day,
      respectively). In slow-transit constipation, a significant decrease of
      contractions' amplitude was also observed. Concerning low-amplitude propagated
      contractions, patients with slow-transit constipation had significantly less
      events with respect to patients with constipation-predominant irritable bowel
      syndrome (46 +/- 7 vs. 87.4 +/- 19, p = 0.015); no differences were found between
      patients with slow-transit constipation and controls and between patients with
      constipation-predominant irritable bowel syndrome and controls. All three groups
      displayed a significant increase of low-amplitude propagated contractions after
      meals (6.3 +/- 2 vs. 18.2 +/- 5 for controls, p < 0.005; 6.4 +/- 1.4 vs. 16.3 +/-
      2.4 for slow-transit constipation, p < 0.005; 10.5 +/- 3.2 vs. 32.6 +/- 7 for
      constipation-predominant irritable bowel syndrome, p = 0.001). CONCLUSIONS: Low
      amplitude propagated contractions may represent an important physiologic motor
      event in constipated patients, reducing the severity of constipation in patients
      with irritable bowel syndrome and preserving a residual colonic propulsive
      activity in patients with slow-transit constipation.

PMID- 14671426
TI  - Penetration of antimicrobial agents into the prostate.
AB  - In the present review article, the penetration of antimicrobial agents into
      prostatic fluid and tissue was examined. Three major factors determining the
      diffusion and concentration of antimicrobial agents in prostatic fluid and tissue
      are the lipid solubility, dissociation constant (pKa) and protein binding. The
      normal pH of human prostatic fluid is 6.5-6.7, and it increases in chronic
      prostatitis, ranging from 7.0 to 8.3. A greater concentration of antimicrobial
      agents in the prostatic fluid occurs in the presence of a pH gradient across the
      membrane separating plasma from prostatic fluid. Of the available antimicrobial
      agents, beta-lactam drugs have a low pKa and poor lipid solubility, and thus
      penetrate poorly into prostatic fluid, expect for some cephalosporins, which
      achieve greater than or equal to the inhibitory concentration. Good to excellent
      penetration into prostatic fluid and tissue has been demonstrated with many
      antimicrobial agents, including tobramycin, netilmicin, tetracyclines,
      macrolides, quinolones, sulfonamides and nitrofurantoin.

PMID- 14671427
TI  - Correlation of meropenem plasma levels with pharmacodynamic requirements in
      critically ill patients receiving continuous veno-venous hemofiltration.
AB  - BACKGROUND: In patients with acute renal failure, the pharmacokinetics of
      meropenem depend on the operational characteristics of the renal replacement
      therapy. Dosage recommendations are based on the correlation of plasma levels
      with pharmacodynamic requirements. METHODS: Eight critically ill patients with
      acute renal failure were treated by continuous veno-venous hemofiltration with a
      filtrate flow of 1,600 ml/h and received 500 mg of meropenem every 12 h. Plasma
      and hemofiltrate concentrations of meropenem at steady state were determined by
      HPLC. RESULTS: Peak levels in plasma amounted to 39.5 +/- 10.5 mg/l (mean +/- SD)
      and trough levels were 2.4 +/- 1.5 mg/l. The minimal inhibitory concentration
      (MIC) for susceptible bacteria (4 mg/l) was covered for 40% of the dosing
      interval or longer in all patients. The MIC for intermediately susceptible
      organisms (8 mg/l) was covered for 33% in 6 of the 8 patients. The elimination
      half-life was prolonged to 3.63 +/- 0.77 h. The sieving coefficient of meropenem
      was 0.91 +/- 0.10 and the recovery in hemofiltrate amounted to 30.9 +/- 11.5% of
      the dose. CONCLUSIONS: A dosage of 500 mg twice daily provides appropriate serum
      levels for the treatment of infections caused by susceptible bacteria. A higher
      dosage is adequate for infections by intermediately susceptible bacteria or for
      renal replacement therapies with markedly higher filtrate flow rates.

PMID- 14671428
TI  - Postantibiotic and sub-MIC effects of benzylpenicillin against Streptococcus
      pneumoniae with different susceptibilities for penicillin.
AB  - BACKGROUND: The purpose of the study was to examine whether penicillin
      susceptible and nonsusceptible strains of Streptococcus pneumoniae exhibited
      different pharmacodynamic responses to benzylpenicillin. METHODS: The
      postantibiotic effects (PAEs) and the postantibiotic sub-MIC effects (PA SMEs)
      were investigated by optical density against strains of S. pneumoniae with
      different susceptibilities to benzylpenicillin. To validate the data, the PAE and
      PA SME of one susceptible and one resistant strain were also tested with the
      viable count method. The post-MIC effects (PMEs) were studied in an in vitro
      kinetic model, simulating human pharmacokinetics with a half-life of 1 h and a
      time above MIC of approximately 20% of 24 h. RESULTS: There were no differences
      with respect to the PAEs, PA SMEs and PMEs of benzylpenicillin for the various
      strains of S. pneumoniae, irrespective of their susceptibility to penicillin. For
      both some of the susceptible and resistant strains investigated, longer PA SMEs
      at 0.2 and 0.3 x MIC were noted, indicating that these parameters might be more
      dependent on the type of strain rather than on the susceptibility status.
      CONCLUSION: No differences in the pharmacodynamic response after similar drug
      exposure were seen for S. pneumoniae strains with different penicillin
      susceptibility.

PMID- 14671429
TI  - In vitro activity of combination therapy with cefepime, piperacillin-tazobactam,
      or meropenem with ciprofloxacin against multidrug-resistant Pseudomonas
      aeruginosa strains.
AB  - The prevalence of multidrug-resistant Pseudomonas aeruginosa strains has been
      increasing every year, and treatment with various antimicrobial combinations has
      been offered alternatively in the clinical practice. The aim of this study was to
      evaluate the in vitro effects of combinations of meropenem, cefepime, or
      piperacillin-tazobactam with ciprofloxacin against multidrug-resistant P.
      aeruginosa strains by the time-kill method. The results show that both the
      combination of two beta lactams with ciprofloxacin and three beta lactams with
      ciprofloxacin against 4 of 5 multidrug-resistant P. aeruginosa strains has no
      effect in vitro. The combination of one beta lactam (meropenem, cefepime,
      piperacillin-tazobactam) with ciprofloxacin has a synergistic effect against one
      strain of multidrug-resistant P. aeruginosa that is ciprofloxacin susceptible and
      resistant to meropenem, cefepime, and piperacillin-tazobactam. None of the
      combinations had an antagonistic effect against these multidrug-resistant
      strains.

PMID- 14671430
TI  - Comparative study of the sensitivity of lymphoblastoid and transformed monocytic
      cell lines to the cytotoxic effects of Viscum album extracts of different origin.
AB  - Viscum album (VA) preparations consist of aqueous extracts of V. album, the
      European mistletoe. VA extracts contain mistletoe lectins, which are members of
      the ribosome-inactivating protein type II family. VA preparations have cytotoxic
      and immunomodulatory properties. Cytotoxicity induced by VA extracts may differ
      greatly according to the origin of the preparation (host tree, fermented extract)
      and the cell type. This work was performed to assess the cytotoxicity of various
      VA preparations, i.e. VA Qu FrF, Qu Spez, M Spez and VA P, in lymphoblastoid and
      monocytic cell lines. VA Qu FrF, Qu Spez and M Spez induced dose-dependent cell
      death and inhibition of cell proliferation in lymphoblastoid T cell lines and in
      transformed monocytic lines. In contrast, the majority of B cell lines tested
      were resistant to cytotoxicity induced by VA extracts. While VA Qu FrF, Qu Spez
      and M Spez were potent inducers of cell death, extracts of VA P, derived from
      mistletoe plants growing on pine trees, failed to induce any cell death in any of
      the cell lines examined.

PMID- 14671431
TI  - The farnesyl protein transferase inhibitor lonafarnib (SCH66336) is an inhibitor
      of multidrug resistance proteins 1 and 2.
AB  - Clinical studies indicate that the farnesyl protein transferase inhibitor
      SCH66336 (lonafarnib), an anticancer agent developed to antagonize oncogenic Ras,
      is generally well tolerated. Lonafarnib has also demonstrated therapeutic synergy
      with coadministered taxanes, vincristine, cisplatin, cyclophosphamide, 5
      fluorouracil (5-FU) and Gleevec. Lonafarnib has recently been shown, in addition,
      to be a potent inhibitor of the transmembrane efflux transporter P-glycoprotein
      (P-gp), which confers cellular resistance to the substrates vincristine, taxol
      and paclitaxel. Treatment with lonafarnib would therefore be predicted to be
      synergistic with these coadministered cancer therapeutics that are substrates of
      P-gp. However, cisplatin, 5-FU and cyclophosphamide are not P-gp substrates, yet
      cisplatin, 5-FU and possibly cyclophosphamide are purported substrates for
      multidrug resistance proteins (MRPs) 1 and 2 (known to cause chemotherapy
      resistance). Lonafarnib is shown here to inhibit the function of MRP1 and MRP2
      with a potency similar to that of cyclosporin A and may therefore cause the
      observed synergy with cisplatin and other agents by inhibiting these MRPs.
      Coadministration of lonafarnib could thus reduce chemotherapy dosage and hence
      produce lower exposure to normal cells and less undesired toxicity.

PMID- 14671432
TI  - Bcl-2 overexpression does not prevent but retards adriamycin toxicity in CC531
      colon carcinoma cells.
AB  - BACKGROUND: The Bcl-2 protein is a critical regulator of susceptibility towards
      cell death induced by antineoplastic drugs. Reduced growth activity and increased
      glutathione (GSH) levels protect against adriamycin toxicity. We recently
      demonstrated statistically significantly reduced growth activity and elevated
      cellular GSH levels in exponentially growing rat CC531 colon carcinoma cells
      overexpressing the full-length human Bcl-2 protein (CCbcl2#A3). METHODS: To
      assess the importance of reduced growth activity or increased GSH levels, we
      determined the mitochondrial function, 24 h after adriamycin treatment, in
      CCbcl2#A3 cells, parental CC531 cells and cells overexpressing the Bcl-2 protein
      lacking the N-terminal BH4 domain (CC Delta BH4): these latter cells contained
      elevated cellular GSH levels but were not reduced in growth activity. RESULTS:
      CCbcl2#A3, but not CC Delta BH4, cells were 3-fold less susceptible than parental
      cells suggestive of a protective role for reduced growth but not for increased
      GSH levels in BCL-2 transfectants. This was confirmed in several growth-inhibited
      CC531 transfectants and in slowly proliferating (ca. 100% confluent) cell
      populations compared to exponentially growing (ca. 50% confluent) cell
      populations. Reduced growth activity might delay the onset of cell death.
      Therefore, we tested the effect of adriamycin five days after treatment. In this
      long-term assay we found no differences between the various cells. CONCLUSION:
      Reduction of growth activity, for instance by an overexpression of the Bcl-2
      protein, only transiently reduced the susceptibility towards adriamycin
      treatment.

PMID- 14671433
TI  - A double-blind, crossover, randomized comparison of granisetron and ramosetron
      for the prevention of acute and delayed cisplatin-induced emesis in patients with
      gastrointestinal cancer: is patient preference a better primary endpoint?
AB  - BACKGROUND: Serotonin receptor antagonists are recommended by the American
      Society of Clinical Oncology for the prevention of acute and delayed chemotherapy
      induced emesis. However, the most effective agent in this class of antiemetic
      drugs for preventing emesis has not been clearly defined. We therefore performed
      a double-blind, crossover, randomized, controlled trial comparing the efficacy of
      granisetron and ramosetron, using patient preference as the primary endpoint.
      METHODS: Thirty patients receiving two courses of combined chemotherapy
      (including > or =60 mg/m(2) cisplatin) for gastric or esophageal cancer were
      randomly assigned to the granisetron-ramosetron group (treatment phase 1:
      granisetron, 3 mg; treatment phase 2: ramosetron, 0.3 mg) or the ramosetron
      granisetron group (treatment phase 1: ramosetron, 0.3 mg; treatment phase 2:
      granisetron, 3 mg). All patients received methylprednisolone sodium, 250 mg i.v.,
      during each treatment phase. RESULTS: The efficacy of granisetron and ramosetron
      was similar in terms of the suppression of emesis and appetite status. However,
      the majority of patients (19/30, 63.3%) expressed a preference for granisetron,
      as compared with 9 patients (30.0%) who preferred ramosetron; 2 patients (6.7%)
      had no preference (chi(2) test: p = 0.008; Fisher's exact test: p = 0.015).
      CONCLUSIONS: (1) A significant proportion of patients prefer granisetron over
      ramosetron for the prevention of chemotherapy-induced emesis. (2) Granisetron and
      ramosetron possess similar effectiveness for the suppression of emesis. (3) The
      variable of 'patient preference' should be accepted as a primary endpoint of
      antiemetic drug efficacy.

PMID- 14671434
TI  - Proinflammatory cytokinemia associated with transient myeloproliferative disorder
      in down syndrome.
AB  - A transient myeloproliferative disorder (TMD) occurs in 10% of the infants with
      Down syndrome. While most cases resolve within a few months, in 20% of them TMDs
      are life-threatening or fatal. We encountered 4 patients with TMD, including 1
      patient who died of liver failure and disseminated intravascular coagulation.
      Suspecting involvement of proinflammatory cytokines, we serially assayed them in
      patients' sera. Cytokines were significantly more abundant in patients than in
      controls. Interleukins 1 and 2, tumor necrosis factor alpha, interferon gamma,
      and granulocyte-macrophage colony-stimulating factor were greatly increased,
      especially in the infant who died. Sustained cytokinemia is likely to participate
      in TMD pathophysiology, and very high serum concentrations might predict a poor
      outcome.

PMID- 14671435
TI  - Plasma arginine and urinary nitrate and nitrite excretion in bronchopulmonary
      dysplasia.
AB  - The aim of this prospective study was to determine whether preterm infants with
      bronchopulmonary dysplasia (BPD) and signs of increased pulmonary artery pressure
      have a deficiency of plasma arginine (ARG) and systemic nitric oxide (NO)
      synthesis. Plasma amino acid concentrations, Doppler pulmonary systolic time
      intervals (ratio of acceleration time and ejection time corrected for heart rate:
      AT/ET(C)) and urinary nitrate and nitrite concentrations were determined at the
      28th day postnatal age and at 36 weeks postmenstrual age in 73 preterm infants
      less than 30 weeks gestational age. The AT/ET(C) ratios were significantly lower
      in infants with BPD (n = 32) compared to controls. However, total amino acid
      concentrations, ARG intake as well as plasma ARG concentrations were not
      different between groups (median (interquartile-range) micromol/l): control: 58
      (42.5-75.5) and 54.5 (42-71) at day 28 and 36 weeks; BPD: 54.5 (31.5-70.5) and 43
      (35-62), respectively. Urinary nitrate and nitrite concentrations, were not
      different between groups at day 28, but significantly higher in infants with BPD
      at 36 weeks (p = 0.014). In conclusion, plasma ARG concentrations and systemic NO
      synthesis were not deficient in preterm infants with BPD and signs of elevated
      pulmonary artery pressure.

PMID- 14671437
TI  - What else can I do for you?

PMID- 14671436
TI  - Hyperglycemia and hyperlipidemia act synergistically to induce renal disease in
      LDL receptor-deficient BALB mice.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease in Western
      countries, but only a portion of diabetic patients develop diabetic nephropathy.
      Dyslipidemia represents an important aspect of the metabolic imbalance in
      diabetic patients. In this study, we addressed the impact of combined
      hyperlipidemia and hyperglycemia on renal pathology. Kidneys from wild-type (WT)
      or LDL receptor-deficient BALB/cBy mice (BALB.LDLR-/-) were examined at 22 weeks
      of age. Diabetes was induced by administration of streptozotocin and mice were
      randomly assigned to either standard chow or Western diet. Chow fed BALB.LDLR-/-
      mice did not demonstrate renal abnormalities, whereas BALB. LDLR-/- mice fed a
      Western diet showed occasional glomerular and tubulointerstitial foam cells.
      Diabetic WT mice had modestly increased glomerular cellularity and extracellular
      matrix. Hyperlipidemic and diabetic BALB.LDLR-/- mice exhibited an increase in
      glomerular cellularity and extracellular matrix, accumulation of glomerular and
      tubulointerstitial foam cells and mesangial lipid deposits. The tubular
      epithelium demonstrated pronounced lipid induced tubular degeneration with
      increased tubular epithelial cell turnover. Hyperlipidemia and hyperglycemia seem
      to act synergistically in inducing renal injury in the BALB.LDLR-/- mouse. This
      model of diabetic nephropathy is unique in its development of tubular lesions and
      may represent a good model for hyperlipidemia-exacerbated diabetic nephropathy.

PMID- 14671439
TI  - Reduce workload intensity with PCTs.

PMID- 14671441
TI  - Stand and deliver.

PMID- 14671443
TI  - Firmly grasp new restraint and seclusion standards.
AB  - Better understand the Joint Commission's updated restraint and seclusion
      standards.

PMID- 14671444
TI  - Don't strike out in union negotiations.
AB  - Examine a case study to see how nurse leaders should proceed in case of a strike.

PMID- 14671445
TI  - How genetics changes daily practice.
AB  - Develop a firmer understanding of the role genetics plays in health and disease,
      and incorporate genetic questions into patient assessment.

PMID- 14671446
TI  - Serving up uncommon service.
AB  - Differentiate between quality and service to improve patient and staff
      satisfaction.

PMID- 14671447
TI  - Prepare to draw Magnet recognition.
AB  - Key nursing representatives from Jewish Hospital of Louisville, Ky., share
      techniques for garnering a successful Magnet appraisal.

PMID- 14671449
TI  - Telehospice carries end-of-life care over the lines.
AB  - Outline the positive and negative predictors of telehospice use, namely its
      impact on organizational and management issues.

PMID- 14671451
TI  - Pre-procedures: make a list and check it twice.
AB  - Review how one facility updated its pre-procedure checklist for transferring
      patients from the telemetry unit to the cardiovascular laboratory.

PMID- 14671453
TI  - Defense styles, personality traits, and psychopathological symptoms in
      nonclinical adolescents.
AB  - The purpose of the present study was to examine relationships between defense
      styles, personality traits, and psychopathological symptoms in nonclinical
      youths. A large sample of adolescents (n = 437) completed the Defense Style
      Questionnaire for Adolescents, the Junior version of the Eysenck Personality
      Questionnaire, and a scale measuring symptoms of DSM-defined disorders. Results
      showed that there were clear relationships between personality traits
      (neuroticism and psychoticism) and defense styles (neurotic and immature defense)
      on the one hand and psychopathological symptoms on the other hand. Most
      importantly, regression analyses indicated that personality traits and defense
      styles both accounted for unique proportions of the variance in
      psychopathological symptoms.

PMID- 14671454
TI  - Pathways to dissociation: intrafamilial versus extrafamilial trauma in juvenile
      delinquents.
AB  - Dissociation is postulated to occur as a function of particular types of child
      abuse or chronic abuse. Additionally, there is an ongoing controversy examining
      the perpetrator's relationship to the victim in the development of dissociation.
      In this study, reports of traumatic events experienced both in the family
      environment and in the community were used to examine the relationship between
      dissociative disorder as defined by DSM-IV (pathological dissociation), and
      dissociation as a defense mechanism. The first objective was to identify whether
      the site of the trauma or the quantity of trauma correlated more significantly
      with symptoms of dissociation. The second objective was to explore a potential
      correlation between topics that participants choose to disclose during a
      standardized Stress Inducing Speech Task (SIST), and symptoms of dissociation.
      The third objective was to examine the relationship between the age of
      occurrence, the duration of trauma, and symptoms of dissociation. Fifty-two
      delinquent juveniles completed measures (including the SCID-D, REM-71, CTQ, CTI,
      SIST) assessing traumatic experiences, psychopathological dissociation, and
      dissociation as defense mechanism. Blind raters scored the SIST for intrafamilial
      and extrafamilial trauma. The perpetrator's relationship to the victim, site of
      the trauma, quantity of the trauma, age of occurrence, and duration of the trauma
      were analyzed by descriptive statistics and Pearson partial correlations.
      Significant correlations were found between symptoms of pathological dissociation
      and intrafamilial trauma. Significant correlations were not found between
      extrafamilial trauma and pathological dissociation and dissociation as defense
      mechanism. All these correlations held constant the chronicity of traumas
      reported. The results obtained in this study through blind and independent
      assessment suggest that special trauma characteristics (i.e., childhood trauma
      perpetrated by a family member) rather than sheer cumulative effects of trauma
      may have greater implications for the development of pathological dissociation.
      The relationships to dissociation as a defense were much weaker.

PMID- 14671455
TI  - Cognitive functioning and employment in severe mental illness.
AB  - This study compared cognitive functioning and symptomatology of unemployed,
      supported employed, and independently employed clients with severe mental
      illness. Unemployed clients who wanted to work (N = 21) were compared with
      clients working in supported employment programs (N = 17) and clients who had
      been working independently for at least 1 year (N = 23) on a neuropsychological
      battery and the Positive and Negative Syndrome Scale. Clients who were unemployed
      had more severe symptoms and worse cognitive functioning on both positive and
      negative symptoms, and almost all domains of cognitive functioning. Supported
      employed clients had more severe psychotic symptoms and worse working memory than
      independently employed clients, but did not differ in negative symptoms or the
      other domains of cognitive functioning, including attention/concentration,
      psychomotor speed, verbal learning and memory, or executive functions. Finally,
      job complexity was correlated with impaired executive functions among clients
      working independently, but not in supported employment. Severe symptoms and
      cognitive impairment may interfere with the ability of some clients with severe
      mental illness to obtain competitive work. Supported employment programs appear
      to work by helping clients compensate for problematic symptoms and cognitive
      impairment and, to a lesser extent, by finding or developing environmental niches
      in which these impairments do not impede their ability to perform the necessary
      job tasks.

PMID- 14671456
TI  - Prevalence and correlates of obesity in a community sample of individuals with
      severe and persistent mental illness.
AB  - Individuals with severe and persistent mental illness (SPMI) have a preponderance
      of weight problems, possibly even greater than the obesity epidemic in the
      general population. Although atypical antipsychotics cause weight gain, their
      contribution to obesity has not been characterized in a community setting where
      individuals may take multiple psychotropics associated with weight gain. Using
      survey information including measured height and weight from a random sample of
      Maryland Medicaid recipients with SPMI, we compared obesity prevalence to the
      National Health and Nutrition Examination Survey (NHANES III) sample and a
      Maryland sample (Behavioral Risk Factor Surveillance System) of the general
      population adjusted to SPMI demographic characteristics. We investigated
      correlates of obesity in the SPMI sample. The results indicate that both men and
      especially women with SPMI had a higher prevalence of obesity than the general
      population; this portends substantial health implications. A fourfold association
      between atypical antipsychotics and prevalent obesity was found in men but not in
      women; further work should clarify mechanisms of obesity in the SPMI.

PMID- 14671457
TI  - Anxiety and hostility in the manifest dreams of schizophrenic patients.
AB  - Aside from delusions, hallucinations, and thought disorders, affective
      disturbances belong to the most prominent symptoms of the schizophrenic process.
      However, nearly no empirical work has been done on the systematic investigation
      of the dream affects of patients with schizophrenia. We compared 96 dreams of 19
      patients with schizophrenia and an equal number of dreams of 19 healthy controls
      collected over an 8-week period by means of the Gottschalk-Gleser Analysis
      Scales. Additionally, central psychopathological syndromes were measured by means
      of the AMDP-scales each day a patient reported a dream. Although cluster analyses
      showed general similarities in the organization of dream affects in the two
      groups, we found differences between patient and control groups in the frequency
      and intensity of anxious and hostile affects. As in delusions of persecution,
      patients experience themselves in their dreams more frequently as victims of
      hostility from outside, which corresponds well with a significantly higher
      intensity of threat anxieties (death, mutilation). On the other hand, value
      anxieties (guilt and separation) are found less frequently in the dreams of
      patients with schizophrenia pointing, together with a less differentiated
      organization of the dream affects, to the typical affective flattening of
      residual syndromes.

PMID- 14671458
TI  - Sampling in difficult to access refugee and immigrant communities.
AB  - We evaluated sampling strategies and trust-building activities in a large
      multiphase epidemiologic study of torture prevalence in populations that were
      difficult to locate and enroll. Refugee groups under study were Somalis from
      Somalia and Oromos from Ethiopia who were living in Minneapolis and St. Paul,
      Minnesota, in 1999-2002. Without a complete sampling frame from which to randomly
      recruit participants, we employed purposive sampling methods. Through comparative
      and statistical analyses, we found no apparent differences between our sample and
      the underlying population and discovered no effects of recruiting methods on
      study outcomes, suggesting that the sample could be analyzed with confidence.
      Ethnographic trust and rapport-building activities among investigators, field
      staff, and immigrant communities made it possible to obtain the sample and gather
      sensitive data. Maintaining a culture of trust was crucial in recovering from
      damaging environmental events that threatened data collection.

PMID- 14671459
TI  - Psychiatric admissions for psychosis in Malmo during the NATO bombing of Kosovo.
AB  - Little is known about the possible mechanisms contributing to increased risk for
      psychosis found among immigrants. We used the NATO bombing campaign of Kosovo as
      a naturalistic experiment to explore the role of potentially stressful aspects of
      minority group status. We examined all patient admissions to the psychiatric
      clinic in Malmo during the months of the NATO campaign in Kosovo in 1999 and
      during control months in 1997. Admission rates showed significantly differing
      trends over time, with an increasing proportion of immigrant patients with
      psychosis admitted during the NATO campaign months and a decreasing proportion of
      such patients admitted during control months. A significantly greater proportion
      of the immigrant patients admitted for psychosis during the NATO campaign months
      versus control months had been exposed to extreme duress before migration.
      Cumulative adversity, either solely or in combination with current stress, may
      possibly contribute to increased risk for psychosis among immigrants.

PMID- 14671460
TI  - Major depression and cognitive decline after 11.5 years: findings from the ECA
      study.

PMID- 14671461
TI  - Disgust sensitivity in psychiatric disorders: a questionnaire study.

PMID- 14671462
TI  - MONICA's quarter century.

PMID- 14671463
TI  - Blood cholesterol level and prevalence of hypercholesterolaemia in developing
      countries: a review of population-based studies carried out from 1979 to 2002.
AB  - BACKGROUND: While the age-specific rates of cardiovascular diseases (CVD) are
      declining in many developed countries, the epidemic is accelerating in most
      developing countries. Elevated serum total cholesterol (TC) is one of the major
      risk factors for atherosclerotic CVD. This review was carried out to describe the
      current situation in mean TC and in the prevalence of hypercholesterolaemia in
      developing countries. DESIGN AND METHODS: A search for papers published in
      medical journals from 1990 to 2002 was performed using the MEDLINE database. A
      total of 37 articles were selected according to previously defined criteria
      containing information on mean blood total cholesterol and/or
      hypercholesterolaemia from 38 developing countries. RESULTS:
      Hypercholesterolaemia is a public health problem in most of the developing
      countries reviewed. A positive association between the population mean TC and the
      GNP per capita was evidenced. CONCLUSIONS: Differences in methodology between
      national surveys make international comparisons difficult. Nevertheless, low-cost
      dietary interventions and the development of primary prevention strategies are
      needed to reduce the already existing public health problem of elevated TC in
      developing countries.

PMID- 14671464
TI  - Relationship of electrocardiographic left ventricular hypertrophy to mortality
      and cardiovascular morbidity in high-risk patients.
AB  - BACKGROUND: The prognostic significance of left ventricular hypertrophy (LVH)
      identified by simple electrocardiographic (ECG) criteria in high-risk patients
      with established cardiovascular (CV) diseases is not clearly understood. DESIGN
      AND METHODS: The Heart Outcomes Prevention Evaluation (HOPE) trial was a
      randomized trial, which evaluated the effects of ramipril and of vitamin E on
      major CV outcomes in 9541 men and women aged 55 years or older with a history of
      coronary artery disease, stroke, peripheral vascular disease or diabetes mellitus
      with at least one additional CV risk factor. Patients were followed for an
      average of 4.5 years. We evaluated the association between simple ECG criteria
      for LVH and the risk for major vascular events, for CV and all-cause mortality
      and for heart failure. RESULTS: Electrocardiographic LVH was present in 793
      (8.3%) HOPE study participants. Of these, 19.0% sustained a major CV event (MI,
      stroke or CV death), 15.6% died and 6.1% developed heart failure compared with
      15.6%, 10.8% and 2.9% respectively of those without ECG-LVH (P = 0.0023; P <
      0.0001 and P < 0.0001). In multivariate analysis ECG-LVH was an independent
      predictor of CV and all-cause death and of heart failure. CONCLUSIONS: In
      patients with CV disease simple, easily applicable ECG criteria for LVH identify
      a subset of individuals at particularly high risk for death and for heart
      failure.

PMID- 14671465
TI  - Influence on lifestyle measures and five-year coronary risk by a comprehensive
      lifestyle intervention programme in patients with coronary heart disease.
AB  - BACKGROUND: Lifestyle measures of coronary heart disease (CHD) prevention have
      been overshadowed by the efficacy of drug treatments. This is particularly the
      case in the setting of secondary prevention where the benefits of lipid lowering,
      anti-platelet and anti-hypertensive drugs have been emphasised in numerous
      trials. Lifestyle measures address several CHD risk factors at once and are
      generally free of serious side effects. OBJECTIVES: The objective of the present
      study was to determine whether a comprehensive programme of lifestyle
      modification could favourably influence dietary and exercise habits in addition
      to smoking cessation over two years. In addition, an attempt was made to evaluate
      if this programme could favourably influence the five-year CHD-risk in the male
      population included in the study. DESIGN: A total of 197 patients with proven
      coronary heart disease were included and randomised to a lifestyle intervention
      programme or to usual care. Follow-up was after a period of two years. METHODS:
      Intervention comprised a low fat diet, regular exercise, smoking cessation,
      psychosocial support and education, delivered by nurses on the rationale for
      pharmacological and lifestyle measures. Usual care comprised follow-up in the
      routine outpatient clinic. Both groups were given the same comprehensive
      medication according to recent guidelines. RESULTS: Patients in the lifestyle
      intervention group reduced the intake of saturated fat, sugar and cholesterol
      (P<0.001), increased their exercise level (P<0.01) and stopped smoking (P<0.05)
      when compared with the usual care group. A sub-analysis of the influence of five
      year CHD calculated risk in males resulted in a relative risk reduction of 22%
      (95% confidence intervals 9-35). Although significant, this result must be
      interpreted with caution due to poor statistical power and reproducibility of the
      method. CONCLUSIONS: In the presence of modern drug treatments for secondary
      cardiovascular disease prevention it remains possible through a favourable diet,
      exercise and smoking cessation to show an additional reduction in the five-year
      risk for CHD in males.

PMID- 14671466
TI  - Blood pressure, serum total cholesterol and contraceptive pill use in 17-year-old
      girls.
AB  - BACKGROUND: Many studies have analysed the relation between cardiovascular risk
      factors and oral contraceptive use in adult women, whereas information on the
      possible health effects of oral contraceptive use during adolescence is lacking.
      DESIGN: The effect of current contraceptive pill use on blood pressure and serum
      total cholesterol concentration was studied in a cross-sectional sample of 120
      adolescent girls with a mean age of 17.4 years. METHODS: After the girls had
      rested for 5 minutes in the sitting position, trained study nurses measured blood
      pressure three times consecutively using a mercury sphygmomanometer. The nurses
      also administered a questionnaire gathering information on the use of oral
      contraceptives, smoking and parental social class. In the morning blood samples
      were taken for the measurement of serum total cholesterol. RESULTS: Mean age (+/
      SD) was 17.4+/-0.8 years. Blood pressure averaged (+/-SD) 108.7+/-9.9 systolic
      and 68.0+/-8.2 mmHg diastolic. Serum total cholesterol was 4.5+/-0.7 mmol/l.
      Forty-nine girls (41%) were taking the contraceptive pill. Of these, 44 (90%)
      were on a combination of ethinyloestradiol (20-35 microg) and a progestogen, four
      (8%) on anti-androgens (35 microg) and one (2%) only on a progestogen. After
      adjustment for age, body mass index, smoking and alcohol status systolic blood
      pressure was 4.6 mmHg higher (95% CI 1.2-8.1; P<0.001) in current pill users than
      in girls not currently on the pill (111.4 versus 106.8 mmHg). Adjusted for the
      aforementioned covariates, diastolic blood pressure was not related to pill use
      (68.2 versus 67.8 mmHg; P=0.7). Serum total cholesterol was 0.43 mmol/l (95% CI
      0.18-0.60; P=0.001) higher among girls using oral contraceptives (4.7 versus 4.3
      mmol/l), irrespective of whether or not the model was adjusted for age, body mass
      index, smoking and alcohol status. CONCLUSIONS: In 17-year-old girls, the use of
      oral contraceptives was associated with a nearly 5 mmHg higher systolic blood
      pressure and a 0.4 mmol/l higher level of serum total cholesterol. The long-term
      prognostic implications of our findings remain to be elucidated.

PMID- 14671467
TI  - Body mass index, coronary heart disease and stroke in Swedish women. A
      prospective 19-year follow-up in the BEDA study.
AB  - BACKGROUND: Although obesity is an important determinant of an unfavourable risk
      factor pattern reported associations between cardiovascular disease and obesity
      in women have been remarkably inconsistent. DESIGN: Longitudinal observational
      population study. METHODS: 1408 Goteborg women without prior cardiovascular
      disease aged 39 to 65 years at baseline were examined with respect to
      cardiovascular risk factors, including body mass index (BMI), in 1979 to 1981.
      Quartiles of BMI were formed of <22 (reference), 22 to 24, 24 to 27, and >27
      kg/m(-2). Follow-up was conducted by use of the Swedish patient and cause
      specific death registers. RESULTS: All trends with respect to incident coronary
      heart disease (CHD--myocardial infarction or revascularization), stroke and all
      cardiovascular disease were positive and significant (P<0.05). No significant
      increase in risk was noted in women with BMI 22-24, compared with women below 22.
      After adjustment for smoking, women with BMI 24 to 27 had a doubled risk of CHD
      [hazard ratio(HR) 2.41 (1.06-5.50)] and of any cardiovascular disease [HR 1.89
      (1.05-3.37)] whereas the increase in stroke risk was non-significant [HR 1.80
      (0.81-4.01)]. Hazard ratios in the heaviest women, with BMI >27, were 3.75 (1.68
      8.37) for CHD, 2.84 (1.32-6.12) for stroke, and 2.98 (1.70-5.21) for any
      cardiovascular disease, after adjustment for smoking. After further adjustment
      for other cardiovascular risk factors, all trends became non-significant.
      However, women with BMI >27 still displayed a statistically independent
      association with respect to coronary disease [adjusted HR 2.67 (1.10-6.47)] and
      all cardiovascular disease [HR 2.23 (1.23-4.04)], but not stroke [HR 2.08 (0.94
      4.61)]. CONCLUSION: The influence of BMI on cardiovascular disease in women may
      be greater than previously thought and, although to a great extent explained by
      the influence of obesity on other risk factors, associated with adverse outcomes
      already at moderately increased body weight.

PMID- 14671468
TI  - The significance of femoral intima-media thickness and plaque scoring in the
      Atorvastatin versus Simvastatin on Atherosclerosis Progression (ASAP) study.
AB  - BACKGROUND: Measurement of intima-media thickness (IMT) is a well established
      surrogate marker for cardiovascular endpoints. We studied the long-term effects
      of statins on femoral IMT and plaque scoring in the Atorvastatin versus
      Simvastatin on Atherosclerosis Progression (ASAP) study. METHODS AND RESULTS:
      Three hundred and twenty-five patients with familial hypercholesterolaemia were
      randomized to either atorvastatin 80 mg/day or simvastatin 40 mg/day. IMT was
      measured at baseline and at 2 years. At baseline, femoral IMT was 1.69 mm in the
      atorvastatin group and 1.61 mm in the simvastatin group; at 2 years, IMT
      increased by 0.06 mm (P=0.24) and 0.15 mm (P=0.012), respectively. No significant
      differences were obvious between these two treatment arms (P=0.26). Femoral
      plaques were present in 64.7% in the atorvastatin group and 56.1% in the
      simvastatin group at baseline; after 2 years, these proportions rose to 66.0%
      (P=0.47) and 67.3% (P=0.02), respectively (P=0.87 between treatment arms).
      Carotid plaques were present in 6.3% versus 4.9%; after 2 years, these
      percentages were 5.0% (P=0.48) versus 5.5% (P=0.71), respectively (P=0.90 between
      treatment arms). CONCLUSION: Our study indicates increased efficacy of
      atorvastatin 80 mg in retarding progression of atherosclerosis in the femoral
      artery compared with simvastatin 40 mg. Interestingly, in the carotid arteries
      these statins influenced IMT to a greater extent, whereas in the femoral artery
      the effects were more pronounced on plaque frequency. These findings underscore
      the generalized effects of lipid lowering on atherosclerosis.

PMID- 14671470
TI  - Prognostic ability of VE/VCO2 slope calculations using different exercise test
      time intervals in subjects with heart failure.
AB  - BACKGROUND: The minute ventilation-carbon dioxide production (VE/VCO2) slope,
      obtained during exercise testing, possesses prognostic value in heart failure
      (HF). The VE-VCO2 relationship is generally linear thereby hypothetically
      producing similar slope values regardless of the exercise-test time interval used
      for calculation. DESIGN: This study assesses the ability of the VE/VCO2 slope,
      calculated at different time intervals throughout a progressive exercise test, to
      predict 1-year cardiac-related hospitalization and mortality in subjects with HF.
      METHODS: Seventy-two subjects underwent symptom-limited exercise testing with
      ventilatory expired gas analysis. Mean age and left ventricular ejection fraction
      for 44 male and 28 female subjects were 51.2 years (+/-13.0) and 27.0% (+/-12.3)
      respectively. The VE/VCO2 slope was calculated from time 0 to 25, 50, 75 and 100%
      of exercise time and subsequently used to create five randomly selected VE/VCO2
      slope categories. RESULTS: (The intraclass correlation coefficient found
      calculation of the VE/VCO2 slope, when divided into quartiles, to be a reliable
      measure (alpha=0.94, P<0.0001). Univariate Cox regression analysis revealed all
      VE/VCO2 slope categories (25-100% and random selections) were significant
      predictors of cardiac-related hospitalization and mortality over a 1-year period.
      Multivariate Cox regression analysis revealed all VE/VCO2 slope categories
      outperformed peak oxygen consumption (VO2) in predicting hospitalization and
      mortality at 1 year. CONCLUSIONS: Although the different classification schemes
      were not identical, these results suggest VE/VCO2 slope maintains prognostic
      significance regardless of exercise-test time interval. Calculation of VE/VCO2
      slope may therefore still be valuable in subjects putting forth a sub-maximal
      effort while effort-dependent measures, such as peak VO2, are not.

PMID- 14671469
TI  - The impact of reimbursement criteria on the appropriateness of 'statin'
      prescribing.
AB  - BACKGROUND: In Belgium, regulations restrict the reimbursement of statins to
      patients with total serum cholesterol above 250 mg/dl (6.41 mmol/l) after a three
      month lipid-lowering diet. We investigated the possible impact of these
      regulations on characteristics of Belgian patients receiving a lipid-lowering
      drug. DESIGN: From 1998 to 2000, standard questionnaires on coronary risk factors
      and treatments with lipid-lowering drugs were completed by 301 GPs sampled at
      random in the 11 Belgian Provinces. Questionnaires had to be completed for 18
      consecutive patients 35 years old or more attending GPs' practices, irrespective
      of the underlying motive for attendance. RESULTS: Of the 5511 patients included
      in the study, 1519 (28%) had established coronary disease or diabetes mellitus,
      or > or = 2 non-cholesterol coronary risk factors. Most (70%) of these patients
      were not treated with a lipid-lowering drug. Only 22% of patients with
      established coronary disease, 10% of patients with diabetes mellitus and 9% of
      patients with > or = 2 coronary risk factors were treated with a statin. Fifty
      nine percent of fibrate users and 50% of statin users had a pre-treatment
      cholesterol level above 250 mg/dl, but had no or only one non-cholesterol
      coronary risk factor. CONCLUSIONS: In Belgium, the majority of patients at higher
      risk of coronary event do not benefit from lipid-lowering drugs, particularly the
      statins. In contrast, one of two statin users and three of five fibrate users
      should probably not receive the drug prescribed. Regulation based on blood
      cholesterol level encourages the overlooking of other risk factors relevant for
      selecting patients having the greatest chance to benefit from statin treatment.

PMID- 14671471
TI  - Factors influencing return to work at one year after coronary bypass graft
      surgery: results of the PERISCOP study.
AB  - PURPOSE: The aim of this study was to evaluate the predictive factors of return
      to work after coronary bypass graft surgery, for the subgroup of professionally
      active patients aged less than 60 years included in the PERISCOP study. METHODS:
      In the principal, prospective, multicentre study, 2065 patients were evaluated
      20+/-10 days after surgery by exercise testing, echocardiogram and 24-h
      ambulatory ECG monitoring. A questionnaire was completed one year after surgery.
      We studied a subgroup of this population, consisting of 530 patients previously
      defined (94.5% men; mean age: 50.5+/-5.8 years). RESULTS: One year after surgery,
      five of these patients had died and 21 were lost to follow-up. Among the
      remaining patients, 340 patients (67.5%) had returned to work. Forty patients
      (7.9%) had retired, 45 (8.9%) were on sick leave, 22 (4.4%) were unemployed, 49
      (9.7%) returned to work after the deadline of 12 months, eight (1.6%) had given
      insufficient information on return to work. In multivariate analysis, the
      independent predictors of a failure to return to work were age >51 years [OR:
      0.39 (95% CI: 0.25-0.59)], being a manual worker [OR: 0.49 (95% CI: 0.31-0.79)],
      being from South East France [(OR: 0.42 (95% CI: 0.23-0.74)], presence of angina
      [OR: 0.40 (95% CI: 0.20-0.82)], dyspnoea [(OR: 0.46 (95% CI: 0.28-0.77)] and a
      duration of exercise <420 s [(OR: 0.50 (95% CI: 0.33-0.76)]. CONCLUSIONS: Return
      to work after coronary bypass graft surgery is observed in 67.5% of cases and
      depends essentially on socio-professional factors and residual symptoms. A
      regional effect was also observed, which requires further study.

PMID- 14671472
TI  - What can we do in secondary prevention of cigarette smoking?
AB  - Cigarette smoking kills about six million smokers per year worldwide, and the
      cigarette has become a symbol of threat to mankind, particularly in
      industrialized countries. Tobacco smoking causes signs of addiction due to
      nicotine, but it is the inhaled and exhaled smoke that causes damage to health if
      cigarette smoking is continued for one or more decades. It is very difficult to
      attain a high efficacy of stopping smoking using methods of primary prevention in
      children and young adults. Secondary and tertiary prevention methods use medical
      and psychological support to the smoker (behavioural and aversion therapy) as
      well as medical advice in combination with drugs such as nicotine replacement or
      bupropion. Using a combination of these methods can increase effectiveness up to
      45%. Use of nicotine replacement therapy (NRT) in combination with medical advice
      is the method of smoking cessation recommended by the World Health Organization.
      Bupropion causes several severe side effects which are not observed with NRT.
      This article reviews various NRT formulations, including chewing gum, patch,
      nasal spray, tablet and inhaler, and our experience of using NRT in medical
      practice, such as adverse events, withdrawal symptoms and the efficacy of NRT in
      patients with coronary heart disease (angina pectoris, cardiac arrhythmias,
      etc.), are briefly mentioned. Overall, we need greater efforts in practising
      primary and secondary prevention among current and future physicians to solve the
      health problems associated with tobacco use in many nations.

PMID- 14671473
TI  - A three-center, randomized, controlled trial of individualized developmental care
      for very low birth weight preterm infants: medical, neurodevelopmental,
      parenting, and caregiving effects.
AB  - Medical, neurodevelopmental, and parenting effects of individualized
      developmental care were investigated in a three-center, randomized, controlled
      trial. A total of 92 preterm infants, weighing less than 1250 g and aged less
      than 28 weeks, participated. Outcome measures included medical,
      neurodevelopmental and family function. Quality of care was also assessed.
      Multivariate analysis of variance investigated group, site, and interaction
      effects; correlation analysis identified individual variable contributions to
      significant effects. The results consistently favored the experimental groups.
      The following contributed to the group effects: shorter duration of parenteral
      feeding, transition to full oral feeding, intensive care, and hospitalization;
      lower incidence of necrotizing enterocolitis; reduced discharge ages and hospital
      charges; improved weight, length, and head circumferences; enhanced autonomic,
      motor, state, attention, and self-regulatory functioning; reduced need for
      facilitation; and lowered family stress and enhanced appreciation of the infant.
      Quality of care was measurably improved. Very low birth weight infants and their
      parents, across diverse settings, may benefit from individualized developmental
      care.

PMID- 14671474
TI  - How do primary care physicians identify young children with developmental delays?
      A national survey.
AB  - Little is known about the current practices of primary care physicians regarding
      developmental surveillance and screening during pediatric preventive care visits.
      We conducted a mailed survey of a random national sample of pediatricians and
      family physicians to describe their practices and identify factors that predict
      use of developmental screening tools, an efficacious way of identifying children
      with developmental delays. Most physicians reviewed developmental milestones and
      prompted parents for developmental concerns at preventive care visits.
      Approximately half of the physicians used a formal developmental screening
      instrument. Female physician gender predicted higher rates of use of screening
      tools for family physicians, but not for pediatricians. Most physicians seemed
      committed to the early diagnosis of developmental delays. Substantial variability
      in surveillance and screening practices, barriers of time and reimbursement, and
      under-reliance on parent-completed questionnaires underscore areas for
      improvement.

PMID- 14671475
TI  - Use of complementary and alternative medicine among children recently diagnosed
      with autistic spectrum disorder.
AB  - This study examined the prevalence and correlates of use of different types of
      complementary and alternative medicine (CAM) among a sample of children with
      suspected or recently diagnosed autism. The authors' review of 284 charts of
      children seen at the Regional Autism Center of The Children's Hospital of
      Philadelphia, Pennsylvania, found that more than 30% of children were using some
      CAM, and that 9% were using potentially harmful CAM. Having an additional
      diagnosis was protective against CAM use and being Latino was associated with CAM
      use. Having seen a prior provider regarding the child's health condition was
      predictive of potentially harmful CAM use. Further research is required on
      cultural differences in treatment decisions about CAM, as well as the reasons for
      the association between the use of prior providers and CAM. The high prevalence
      of CAM use among a recently diagnosed sample indicates that clinicians should
      discuss CAM early in the assessment process.

PMID- 14671476
TI  - Exposure to violence and psychosocial adjustment among urban school-aged
      children.
AB  - This study determines the relationship between psychosocial adjustment in school
      aged children and one aspect of exposure to violence, the proximity of exposure,
      in terms of (1) "physical" proximity and (2) "emotional" proximity to the victims
      of violence. A convenience sample of 175 children aged 9 to 12 years from a
      primary care clinic of a large urban hospital were interviewed about their
      exposure to violence using the Children's Report of Exposure to Violence.
      Psychosocial adjustment was measured through maternal reports using the Child
      Behavior Checklist (CBCL) and the Personal Adjustment and Role Skills Scale (PARS
      III). Children were categorized into three groups according to their closest
      proximity to exposure to violence ("victim" > "witness" > exposure through other
      people's "report") and two groups according to emotional proximity (victim was a
      "familiar person" or "stranger"). All children (23/175) who scored above the CBCL
      clinical cutoff (T score > 63) were witnesses or victims of violence. The CBCL
      total T scores (higher score = more maladjustment) showed that the "victims"
      group (mean 52.4) scored significantly higher than the "witness" group (mean
      50.0) and "report" group (mean 47.4). The PARS III total scores (lower scores =
      more maladjustment) showed that the "victims" group (mean 87.5) scored
      significantly lower than the "witness" group (mean 93.1) and "report" group (mean
      98.2). The relationship of the child to the victim was not associated with
      significantly different CBCL and PARS III scores. Children exposed to more
      proximal forms of violence as victims or witnesses exhibited more psychosocial
      maladjustment.

PMID- 14671477
TI  - Silent victims: a decade later.

PMID- 14671478
TI  - The difficult parent: a reflective pediatrician's response.

PMID- 14671479
TI  - Single-case experimental designs: applications in developmental-behavioral
      pediatrics.
AB  - This article discusses single-case experimental designs (SCEDs) and their
      relevance to developmental-behavioral pediatrics. Information concerning SCEDs
      have not been described in the Journal of Developmental and Behavioral
      Pediatrics, despite its relevance to the field. General issues related to the
      underlying logic and applications of SCEDs are reviewed with examples selected
      from the literature to illustrate the strengths and weaknesses of different
      design strategies. It is suggested that SCEDs can be a useful alternative to
      traditional between-group designs for clinical and evaluation research because
      the unit of the analysis is the individual; therefore the feedback to clinicians
      and families is direct about the effectiveness of a behavioral intervention or
      medication for that individual. In the field of developmental-behavioral
      pediatrics, SCEDs can be especially useful in the management of vague symptoms or
      poorly defined diseases to improve the confidence in a treatment decision for an
      individual patient. This report is intended to facilitate the understanding and
      use of single-case methodology so that clinicians are aware that flexible, true
      experiential designs exist to fill the gap in knowledge and also "do the best for
      my patient."

PMID- 14671480
TI  - Risk-taking behavior, subintentioned death and suicide.

PMID- 14671482
TI  - Virtual colonoscopy compared with conventional colonoscopy for stricturing
      postoperative recurrence in Crohn's disease.
AB  - BACKGROUND: The place of virtual colonoscopy (VC) in patients with Crohn's
      disease (CD) requiring endoscopic follow-up after surgery is unknown. The authors
      compared findings from VC versus conventional colonoscopy (CC) for assessing the
      postoperative recurrence of CD. METHODS: Sixteen patients with ileocolonic
      anastomosis for CD were prospectively enrolled from January 2001 to January 2002.
      Recurrence was assessed by CC according to Rutgeerts et al. VC was performed with
      a computed tomography scanner, with images examined by three radiologists who
      were unaware of the endoscopic findings. RESULTS: CC showed perianastomotic
      recurrence in 15 of 16 patients. Perianastomotic narrowing or stenosis was
      detected by VC in 11 of these 15 patients. There were 11 true positive, 1 true
      negative, 0 false-positive, and 4 false-negative findings (73% sensitivity, 100%
      specificity, 100% positive predictive value, 20% negative predictive value, 75%
      accuracy). Among the eight patients showing a rigid stenosis of the anastomosis
      not allowing passage of the colonoscope, VC detected narrowing or stenosis in
      seven patients. CONCLUSIONS: The current findings suggest that although the
      widespread use of VC in CD is currently not indicated because of possible false
      negative findings, this technique may represent an alternative to CC in
      noncompliant postsurgical patients with a rigid stenosis not allowing passage of
      the endoscope.

PMID- 14671483
TI  - Gross versus microscopic pancolitis and the occurrence of neoplasia in ulcerative
      colitis.
AB  - OBJECTIVE: The gross extent of ulcerative colitis (UC) is a recognized risk
      factor for the development of colitis-related dysplasia and colorectal cancer
      (CRC). The risk of neoplasia associated with the microscopic extent of colitis is
      unknown. The aim of this study was to describe the gross and microscopic extent
      of colitis in patients with UC-related dysplasia/CRC. METHODS: All patients who
      underwent colectomy at our institution between 1992-2001 with colitis-related
      dysplasia/CRC were identified. Histological sections from each colectomy specimen
      were reviewed for the microscopic extent of colitis and the location of all
      lesions with dysplasia/CRC. RESULTS: Thirty-six patients with colitis-related
      dysplasia/CRC were identified of whom 30 had slides available for review. Gross
      pancolitis was identified in 19 patients, though microscopic pancolitis was
      evident in all 30 patients. Among the 11 patients with only distal gross colitis,
      4/15 neoplastic lesions were proximal to the area of gross involvement.
      CONCLUSIONS: UC-related neoplasia can occur in areas of the colon not grossly
      involved with colitis, though it did not occur in any patients without
      microscopic pancolitis. To devise rational cancer surveillance guidelines,
      further studies are needed to determine the risk of colitis-related neoplasia in
      patients with microscopic pancolitis but limited gross disease.

PMID- 14671484
TI  - Evaluation of educational programs in inflammatory bowel disease.
AB  - BACKGROUND: Little is known about the status of patient knowledge in inflammatory
      bowel disease (IBD) and potential benefit of educational programs. The authors
      conducted this study to assess 1) the knowledge of IBD of participants attending
      educational workshops offered to the public and 2) the effect of the workshop on
      participants' knowledge level. METHODS: Workshops on IBD were offered to the
      public at nine communities in the United States. Each workshop consisted of a
      combination of 3 hours of presentations and question-and-answer sessions.
      Participants, including patients with IBD and their parents, spouses, siblings,
      friends, and significant others, were asked to complete the Crohn's and Colitis
      Knowledge Score questionnaires just before (Q1) and immediately after (Q2) the
      workshop and approximately 3 months later (Q3). The authors scored one point for
      each correct answer to the 30 questions in the Crohn's and Colitis Knowledge
      Score. RESULTS: Of the 734 who completed the Q1, 33.7% gave correct answers for
      questions about IBD complications, 36.2% for treatment, 61.4% for general
      knowledge, and 64.8% for diet. After the workshop, the proportion for these four
      knowledge areas increased by 11.0% to 19%. For the participants who completed all
      of the three questionnaires and answered all the 30 questions (N=59), the mean
      score was 18 at Q1, 22 at Q2 (p<0.001, Q2 vs. Q1), and 21 at Q3 (p<0.001, Q3 vs.
      Q1). CONCLUSIONS: The public's general knowledge of IBD is low. Educational
      programs oriented toward IBD improve participant's knowledge, and the knowledge
      they acquired is retained for at least 3 months.

PMID- 14671485
TI  - The intestinal anti-inflammatory activity of UR-12746S on reactivated
      experimental colitis is mediated through downregulation of cytokine production.
AB  - BACKGROUND: UR-12746S (dersalazine sodium) is cleaved by colonic bacteria
      delivering the PAF antagonist UR-12715 and 5-ASA. This study describes the anti
      inflammatory activity of UR-12746S in an experimental model of reactivated
      colitis and its effects on cytokine production. METHODS: Rats were initially
      rendered colitic by a colonic instillation of 10 mg of trinitrobenzenesulphonic
      acid (TNBS) dissolved in 0.25 ml of 50 % ethanol, and colitis was reactivated two
      weeks after by a second administration of the same dose of TNBS. Two groups of
      colitic rats received UR-12746S (25 and 50 mg/kg daily, p.o.) and colonic damage
      was evaluated every week for 4 weeks. Different biochemical markers of colonic
      inflammation were assayed: MPO activity and cytokine (IL-1beta and TNFalpha)
      levels. Also, the in vitro effects of UR-12715 and 5-ASA on cytokine production
      were assayed. RESULTS: UR-12746S showed anti-inflammatory effect in reactivated
      colitis in rats, as evidenced by a significant reduction in MPO activity. Both
      doses of UR-12746S decreased IL-1beta production, while only the highest dose
      assayed inhibited TNFalpha production. In vitro studies revealed that UR-12715 or
      5-ASA (from 10(-6) to 10(-4) M) inhibited IL-8 production (30-40%) in HT-29 cells
      when incubated with LPS. This inhibitory effect was enhanced when both compounds
      were administered simultaneously at 10(-4) M. In addition, UR-12715 inhibited IL
      1beta or TNFalpha production in THP-1 or U937 cells, respectively, when these
      cells were stimulated by PMA and LPS; whereas 5-ASA only showed a weak effect in
      inhibiting IL-1beta production. CONCLUSION: UR-12746S was able to prevent relapse
      in experimental colitis and inhibition of proinflammatory cytokine production
      participates in the intestinal anti-inflammatory activity exerted by this
      compound.

PMID- 14671486
TI  - Dietary Dunaliella bardawil, a beta-carotene-rich alga, protects against acetic
      acid-induced small bowel inflammation in rats.
AB  - BACKGROUND: Reactive oxygen species mediate tissue injury in inflammatory bowel
      disease. Beta-carotene is known as a potent free radical quencher and
      antioxidant. AIM: The authors evaluated the efficacy of prefeeding Dunaliella
      bardawil, rich in beta-carotene, to ameliorate acid-induced enteritis in a rat
      model. METHODS: Enteritis was induced in female Sprague-Dawley rats by injection
      of 2 mL acetic acid (0.67 mol/L) to a ligated duodenal loop following 10 weeks of
      feeding diets containing beta-carotene and compared with various controls. The
      effects of beta-carotene were evaluated by changes in myeloperoxidase activity,
      histology, and histomorphometry. RESULTS: Feeding beta-carotene resulted in
      suppressed mucosal myeloperoxidase activity, both basal and that induced by
      acetic acid injection. Acetic acid treatment induced major histopathologic
      changes in the duodenal mucosa, including small, irregular, and distorted villi;
      damage to the epithelium; edema of the lamina propria; accumulation of
      inflammatory cells; and hemorrhage. Beta-carotene treatment prevented these acid
      induced histopathologic changes, and this was confirmed by histomorphometry of
      the villi. CONCLUSIONS: These results demonstrate the effectiveness of beta
      carotene in a rat model as a prophylactic dietary measure in reducing the effects
      of acid-induced enteritis and raise the possibility that patients with Crohn's
      disease may benefit from the consumption of natural beta-carotene.

PMID- 14671487
TI  - Inflammatory bowel disease in African Americans.
AB  - Ulcerative colitis (UC) and Crohn's disease (CD) are idiopathic inflammatory
      disorders of the gastrointestinal tract. The two disorders encompass a wide
      spectrum of clinical presentations and are diagnosed on the basis of their
      clinical, endoscopic, radiologic, and histologic features. Combined, the two
      disorders affect approximately 800,000 patients in the United States. An
      assessment of the epidemiology of these disorders is complicated by a wide range
      of factors including the absence of population based registries in ethnically
      diverse regions, the use of retrospective data, and highly variable clinical
      presentations which may delay or obscure the diagnosis. In this paper we review
      the available data regarding the epidemiology, clinical presentation, and
      clinical course of inflammatory bowel disease in African Americans.

PMID- 14671488
TI  - Monitoring of AZA/6-MP treatment in children with IBD is necessary.

PMID- 14671489
TI  - Monitoring of azathioprine/6-mercaptopurine treatment in children with IBD is not
      necessary.

PMID- 14671491
TI  - Antisecretory factor-induced regression of Crohn's disease in a weak responder to
      conventional pharmacological treatment.

PMID- 14671493
TI  - Presentation of the Southern Society for Clinical Investigation 2003 Founders'
      Medal to Dr. Jules B. Puschett.

PMID- 14671494
TI  - Southern Society for Clinical Investigation Founders' Medal recipient's address.

PMID- 14671495
TI  - Celebrating the SSCI: the drug discovery pathway: challenges and pitfalls.

PMID- 14671496
TI  - Does it matter how we lower blood pressure?
AB  - The risk of cardiovascular disease in patients with hypertension has decreased
      dramatically over the last 40 years. This impressive reduction is attributable in
      part to an increased awareness of the risk related to hypertension, to an
      emphasis on treatment to lower target blood pressures, and to the development of
      more effective antihypertensive drugs. Several recent studies have revealed
      potential blood pressure-independent protective effects of some agents, creating
      a debate on whether different drug classes actually confer a beneficial effect
      beyond the effect on blood pressure. Studies are needed to assess the
      contributions of blood pressure and its components versus blood pressure
      independent effects on the reduction of cardiovascular risk.

PMID- 14671498
TI  - Simultaneous testing of the heparin effect on the soluble phase and platelet
      component of hemostasis.
AB  - BACKGROUND: This study assessed the anticoagulant effect of heparin on both
      platelet activity and soluble phase coagulation. METHODS AND RESULTS: Blood
      samples were collected from 32 patients undergoing cardiac catheterization before
      and 5 minutes after a heparin injection (2000 U). Activated clotting time (ACT),
      activated partial thromboplastin time (aPTT), and whole blood platelet
      aggregation [adenosine diphosphate (ADP) and collagen] were compared with the
      flow device variables platelet hemostasis time (PHT) and collagen-induced
      thrombus formation (CITF). Before heparin, all patients had a normal aPTT and all
      but 1 had a normal ACT. After heparin, all patients showed a prolonged aPTT and
      ACT. In contrast, the flow device showed considerable variability after heparin.
      Only 47% of patients increased both PHT and CITF above the upper limit of normal,
      and 13% did not prolong either. After heparin, enhanced platelet aggregation to
      ADP and collagen occurred in 53% and 63% of patients, respectively. CONCLUSIONS:
      Although patients seem to have an anticoagulant effect after heparin based on ACT
      and aPTT results, the flow device identified a lack of any hemostatic impairment
      in 25 to 41% of patients. These findings probably reflect the variable effect of
      heparin on platelet function and may explain the poor heparin effect or,
      alternatively, the excessive bleeding after heparin administration that occurs in
      some patients.

PMID- 14671499
TI  - Exposure to radiologic contrast media and an increased risk of treated end-stage
      renal disease.
AB  - BACKGROUND: Radiologic contrast media can cause acute renal failure, but whether
      their repeated use is associated with end-stage renal disease (ESRD) is unknown.
      METHODS: We compared 716 incident case subjects of treated ESRD with 361 control
      subjects, frequency matched on age, drawn from the general population (age, 20-65
      years). Participants were interviewed by telephone regarding their previous
      exposure (before initiation of dialysis for case subjects and the study interview
      for control subject) to various imaging procedures. RESULTS: As expected, the
      case subjects reported having more imaging procedures of the kidneys than did
      control subjects. Excluding persons who had been subjected to examinations of
      their kidney from the analysis and adjusting for ultrasound examinations and
      several possible confounders, persons who had a history of one [odds ratio (OR),
      2.0; 95% confidence interval (CI), 1.0, 4.0], 2 or 3 (OR, 2.6; 95% CI, 1.2,5.9),
      or 4 or more (OR, 3.6; 95% CI, 1.0, 12.5) radiocontrast examinations were at
      higher risk of treated ESRD than persons who reported not having had such
      procedures. Ultrasound examinations and a history of barium enema were not
      associated with an increased risk of treated ESRD. CONCLUSION: In the current
      study, a graded association was present between increasing exposure to radiologic
      contrast media and higher risk of treated ESRD. Whether exposure to contrast
      media accelerates progression to ESRD or is merely a noncausal accompaniment to
      multiple disease processes occurring concurrently cannot be determined from our
      observational data. However, if these results are confirmed in future prospective
      studies, they will have important clinical implications.

PMID- 14671500
TI  - Current issues in the management of bacterial respiratory tract disease: the
      challenge of antibacterial resistance.
AB  - The worldwide burden of respiratory tract disease is enormous. Resistance to
      penicillins, macrolides, and cephalosporins is now detected among the leading
      bacterial pathogens that cause respiratory tract infections (RTIs)-Streptococcus
      pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The increasing
      role of atypical/intracellular pathogens (eg, Chlamydia pneumoniae, Mycoplasma
      pneumoniae, Legionella pneumophila) in RTIs, as well as their increase in
      antibiotic resistance prevalence, continues to be of great concern. More recently
      introduced treatment options for RTIs include the newer respiratory
      fluoroquinolones, along with the macrolides and azalides. Although these agents
      demonstrate good activity against common respiratory pathogens, reduced
      susceptibility to these agents has been reported. The ketolides are recently
      developed antibacterial agents with targeted-spectrum activity against common
      respiratory tract pathogens, including atypical/intracellular pathogens, and a
      low potential for inducing resistance. These promising new drugs have shown in
      vitro and in vivo efficacy in the treatment of community-acquired RTIs, such as
      community-acquired pneumonia, acute exacerbations of chronic bronchitis, and
      acute bacterial maxillary sinusitis.

PMID- 14671501
TI  - The current status of immune modulating therapy for myocarditis: a case of acute
      parvovirus myocarditis treated with intravenous immunoglobulin.
AB  - We present a case of a patient who presented with a febrile illness without
      obvious source initially, who developed profound cardiac decompensation and left
      ventricular dysfunction. Viral titers obtained during the course of illness
      confirmed parvovirus infection. Intravenous aggressive immunoglobulins and
      medical therapy for heart failure resulted in stabilization and, ultimately, a
      complete recovery. Recent data from clinical trials are discussed regarding the
      utility of immunoglobulins in the treatment of myocarditis and heart failure.

PMID- 14671502
TI  - A giant left ventricular pseudoaneurysm as a late sequela of aortic valve
      endocarditis.
AB  - Left ventricular pseudoaneurysm is an uncommon complication of infective
      endocarditis, usually presenting within several weeks of the infective episode.
      We describe a 37-year-old man who presented with exertional dyspnea nearly a year
      after a prolonged hospitalization for lung abscess. Imaging studies showed new
      aortic valve regurgitation and a giant pseudoaneurysm extending inferoposteriorly
      from the left ventricle. At thoracotomy, a perforated aortic valve was found,
      suggesting a healed endocarditis. The patient underwent successful aneurysmectomy
      and patch closure with aortic valve repair. This case underscores the potential
      for very late nonvalvular cardiac complications of infective endocarditis and is
      also distinctive because of the large size of the pseudoaneurysm.

PMID- 14671503
TI  - Quinine induced HUS-TTP: an unusual presentation.
AB  - A 67-year-old white woman developed severe nausea, vomiting, diffuse abdominal
      cramping pain, and blurred vision followed by a syncopal episode after taking 1
      tablet of quinine for leg cramps. Examination was significant for fever, elevated
      blood pressure, and confusion without any focal neurological deficits. Laboratory
      studies showed markedly elevated liver enzymes, elevated lactate dehydrogenase,
      anemia, thrombocytopenia, and acute renal failure. Peripheral smear showed many
      schistocytes and burr cells. She later recalled taking quinine more than 40 years
      before while on a trip to the Philippines. The patient was treated with 7
      sessions of plasmapheresis with a rapid normalization of her hematological
      parameters. Three weeks of dialysis support were required before return of renal
      function to baseline. Re-exposure to quinine can cause a rapid onset of hemolytic
      uremic syndrome-like syndrome. We are not aware of any cases of hemolytic uremic
      syndrome-thrombotic thrombocytopenic purpura in response to re-exposure to a
      single tablet of the drug 40 years after first use.

PMID- 14671504
TI  - The epidemiology and natural history of HIV/HBV and HIV/HCV co-infections.
AB  - Both hepatitis B virus (HBV) and hepatitis C virus (HCV) are more common in HIV
      infected individuals than in the general population as a result of shared risk
      factors for viral acquisition. Populations of injecting drug users are at
      particularly high risk for HIV/HCV co-infection. Co-infection with HIV results in
      greater likelihood of chronicity and enhanced viral replication in the setting of
      both HBV and HCV infections. Current evidence suggests that HIV infection may
      have a negative impact on HBV-related liver disease progression, although the
      mechanisms for this are unclear. HBV seems to have little impact on the
      progression of HIV disease. HIV co-infection hastens HCV-related liver disease
      with faster progression to cirrhosis, end-stage liver disease and occurrence of
      hepatocellular carcinoma. There is still conflicting evidence on the impact of
      HCV on HIV progression with inconsistent results from cohort studies. Long-term
      follow-up of highly active antiretroviral therapy (HAART)-treated patients will
      help elucidate this further. Antiretroviral agents have little long-term impact
      on HCV viraemia, although some have significant anti-HBV activity. Morbidity and
      mortality from end-stage liver disease in HIV-infected individuals is increasing
      and every effort should be made to identify, educate and treat as appropriate
      those with HBV or HCV co-infection.

PMID- 14671505
TI  - Summary of BHIVA guidelines for HIV and hepatitis B or C co-infection.
AB  - The British HIV Association (BHIVA) guidelines on HIV/hepatitis B virus (HBV) and
      HIV/hepatitis C virus (HCV) co-infection provide comprehensive and up-to-date
      information on how best to manage this difficult group of patients.

PMID- 14671506
TI  - Issues in diagnostic testing and monitoring in HIV/viral hepatitis co-infection.
AB  - Co-infection with HIV and hepatitis B (HBV)/ hepatitis C virus (HCV) occurs
      commonly due to similar routes of transmission. Both hepatotropic viruses can
      cause a severe clinical picture in HIV-infected individuals with rapid
      progression of liver disease, cirrhosis and increased mortality. Fortunately,
      treatment options of HBV and HCV are becoming well established and may have a
      clinical impact in slowing disease progression. This, coupled with the fact that
      highly active antiretroviral therapy (HAART) has increased the life expectancy of
      HIV-infected patients stresses the importance of management of concurrent
      illnesses such as HBV and HCV infection, taking into consideration
      pharmacokinetic interaction with components of HAART regimens.

PMID- 14671507
TI  - Antiretroviral therapy-related hepatotoxicity: predictors and clinical
      management.
AB  - Severe hepatotoxicity develops in 5-10% of people with HIV infection in the first
      12 months following initiation of highly-active antiretroviral therapy (HAART),
      with continuing risk in subsequent years. The major risk factors for severe
      hepatotoxicity are underlying chronic viral hepatitis, abnormal baseline levels
      of serum hepatic transaminases, and nevirapine or high-dose ritonavir-containing
      antiretroviral therapy regimens. The vast majority of severe hepatotoxicity cases
      are not associated with development of symptoms of acute hepatitis or other
      adverse hepatic outcomes and resolve within a few months. Antiretroviral therapy
      should be discontinued in association with grade 4 elevations in serum hepatic
      transaminase measurements, hyperlactataemia, symptoms of acute hepatitis, or
      features of drug hypersensitivity.

PMID- 14671508
TI  - Ambulatory intragastric pH monitoring: clinical laboratory to clinical practice.
AB  - Intragastric pH monitoring has become an important tool, used in the clinical
      laboratory to assess pharmacodynamic profiles of antisecretory agents. The
      technique is standardized, reproducible, and reliable. We have been able to
      compare antisecretory agents head-to-head, develop an understanding of
      interindividual variability in pH control with proton pump inhibitors, evaluate
      the role of H. pylori and its effect on intragastric pH, and gain insight into
      the potential role of genetic variation in cytochrome p450 status and its effect
      on pH control. These laboratory experiences can be used in clinical practice to
      aid in management of patients with gastroesophageal reflux disease.

PMID- 14671509
TI  - Alternative dosing for PPI therapy: rationale and options.
AB  - The target goal for all acid suppressive therapy is to optimize control of
      intragastric pH over extended periods of time. A somewhat axiomatic paradigm has
      been that effective control of gastric acid production is associated with optimal
      outcome in acid-related diseases. The proton pump inhibitor (PPI) class of
      therapy has shown superiority for effective control of acid and healing of
      related diseases. Traditional delivery of PPIs may not be a viable option for all
      patients. Therefore, a clear understanding of alternative dosing formulations and
      related efficacies is key in order for the clinician to select the most
      appropriate agent and strategy to optimize outcomes and cost-effectiveness for
      each patient.

PMID- 14671510
TI  - Epigastric pain in dyspepsia and reflux disease.
AB  - Epigastric pain may occur as a specific and localized symptom, as part of a group
      of symptoms that include heartburn, or in association with bloating or early
      satiety. The current classification (Rome II) characterizes ulcer-like dyspepsia
      by predominant pain centered in the upper abdomen and characterizes dysmotility
      like dyspepsia by discomfort. The large number of patients presenting with
      epigastric pain has led to the development of empirical strategies.

PMID- 14671511
TI  - Sleep issues in gastroesophageal reflux disease: beyond simple heartburn control.
AB  - There is a burgeoning interest in the relationship between sleep-related
      gastroesophageal reflux (GER) and the development of esophageal and extra
      esophageal complications. The physiological changes associated with sleep, such
      as suspension of the regulation of body temperature, may influence nocturnal GER
      and esophageal acid clearance. Data indicate that sleep induces considerable risk
      of prolonged acid mucosal contact and facilitates the occurrence of proximal
      migration of acid, thereby increasing the probability of pulmonary aspiration.
      Nocturnal GER can lead to the development of esophagitis and other extra
      esophageal complications, such as exacerbation of asthmatic symptoms.

PMID- 14671512
TI  - The role of proton pump inhibitors in NSAID-associated gastropathy and upper
      gastrointestinal symptoms.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used drugs in
      the United States. Ulcers are found with an endoscopy in 15%-30% of patients who
      are using NSAIDs regularly, and the annual incidence of upper gastrointestinal
      (GI) clinical events is 2.5%-4.5% among those who use NSAIDs regularly. Upper GI
      symptoms, such as dyspepsia, also occur in up to 60% of patients taking NSAIDs.
      H2-receptor antagonists when used at standard doses are not effective at
      preventing gastric ulcers resulting from the use of NSAIDs. Misoprostol
      effectively decreases NSAID-induced ulcers and GI complications, but issues of
      compliance (multiple daily doses) and side effects (eg, diarrhea and dyspepsia)
      may limit its use. Once-daily therapy with proton pump inhibitors has been
      documented to significantly decrease the development of NSAID-associated ulcers
      in endoscopic studies, reduce the rate of NSAID-related ulcer complications, and
      reduce upper GI symptoms in NSAID users.

PMID- 14671513
TI  - A prospective arthroscopic study of acute first-time anterior shoulder
      dislocation in the young: a five-year follow-up study.
AB  - A prospective arthroscopic study was conducted on 31 patients with an acute first
      time anterior shoulder dislocation (AFASD). The patients were aged between 16 and
      39 years. The mean age was 24 years. None had a history of shoulder problems. All
      were evaluated after 1, 2, and 5 years. The Constant score, Rowe score,
      recurrence rate, and instability rate were evaluated, as well as patient
      satisfaction and sports participation. We conclude that after a prolonged follow
      up, an increase in the instability rate in young patients with AFASD may become
      apparent. The overall instability rate was 55% (17/31) after 5-year follow-up. In
      patients aged younger than 18 years the instability rate was 71% (5/7). Age was
      the only predictive factor in shoulder instability. The mean Rowe score was 87
      (range, 57-100; SD, 14). Three patients had undergone a stabilization operation
      at the 5-year follow-up. The intraarticular pathology found at arthroscopy was
      not predictive of shoulder instability. We could not find a correlation between
      sporting activities and shoulder instability. On the basis of our results, it
      appears unlikely that arthroscopic lavage reduces redislocation rates after AFASD
      in the young patient.

PMID- 14671514
TI  - Arthroscopic Bankart reconstruction with a bioabsorbable anchor.
AB  - This study evaluated the clinical effectiveness of a poly-l-lactic acid
      biodegradable suture anchor for arthroscopic Bankart reconstruction with a
      prospective multicenter study. Inclusion criteria were one or more episodes of
      traumatic dislocation or multiple posttraumatic subluxations as a manifestation
      of unidirectional anterior instability. Exclusion criteria were significant
      glenoid bone deficiency, large Hill-Sachs lesions, rotator cuff tears,
      multidirectional instability, posterior labrum tears, or biceps ruptures. Fifty
      seven patients were followed up for a mean of 24 months. Postoperative
      apprehension tests were negative in all but two. Motion improved from 155 degrees
      preoperatively to a mean of 175 degrees postoperatively. Four patients had
      postoperative instability symptoms (two dislocators and two with subluxations).
      Postoperative radiographs demonstrated no lytic or resorptive bone changes from
      the suture anchors. The mean postoperative Rowe score was 93. The biodegradable
      suture anchor achieved good clinical results when used for arthroscopic Bankart
      reconstruction with no material-related adverse events.

PMID- 14671515
TI  - Latissimus dorsi tendon transfer for massive rotator cuff tears: a cadaveric
      study.
AB  - Certain massive defects of the rotator cuff tendinous insertion cannot be
      repaired primarily to the greater tuberosity. If restoration of strength is an
      important treatment goal to the patient, then a tendon transfer may be
      considered. Ten cadaver shoulders were dissected to define the anatomy of the
      latissimus dorsi tendon (LDT) and its distance relationship to the axillary and
      radial nerves with the arm in various positions. The axillary nerve lies superior
      to the LDT insertion, and the radial nerve passes medial and inferior to the LDT
      insertion. With the arm internally rotated and the shoulder flexed, the distances
      from the axillary and radial nerves to the LDT insertion were 2.3 cm and 2.8 cm,
      respectively. With the arm internally rotated and the shoulder abducted, the
      distances from the axillary and radial nerves to the LDT insertion were 1.8 cm
      and 2.0 cm, respectively. Understanding specific anatomic relationships is one of
      the factors contributing to the safety of the LDT transfer procedure with respect
      to nerve injury.

PMID- 14671516
TI  - Use of 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET)
      imaging for the evaluation of muscle metabolic activity in ruptured rotator
      cuffs: Identification of shoulder muscles by fusion imaging studies involving
      both FDG PET and magnetic resonance imaging.
AB  - The uptake of 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) into shoulder muscles was
      studied in 11 patients with rotator cuff tears. FDG was injected under resting
      conditions, and cuff muscle exercises were performed followed by evaluation of
      the standardized uptake value (SUV) in shoulder muscles bilaterally. Analysis was
      performed with a subtracted SUV, obtained by subtracting the SUV of the muscle at
      rest from that after exercise. Fusion imaging studies involving FDG positron
      emission tomography (PET) and magnetic resonance imaging would provide a novel
      strategy with the potential of improving on the limited resolution of PET images.
      In this study this relatively new strategy revealed a similar decrease in the
      supraspinatus SUV in cases involving both complete and partial tears. The SUV in
      the infraspinatus and subscapularis also decreased, regardless of whether these
      muscles were intact or ruptured; the SUV in the deltoid remained basically
      unchanged. With the use of this exercise protocol, FDG PET might prove useful for
      objective evaluation of rotator cuff muscle activity.

PMID- 14671517
TI  - Influence of cuff muscle fatty degeneration on anatomic and functional outcomes
      after simple suture of full-thickness tears.
AB  - Two hundred twenty shoulders with a rotator cuff tear repaired by simple tendon
      to-bone suture were analyzed to determine whether the severity of presurgical
      fatty degeneration had an influence on their anatomic and functional outcome.
      Fatty degeneration was evaluated for each muscle with the 5-stage grading system
      developed by Goutallier et al. A global fatty degeneration index (GFDI), the mean
      value of the 3 muscles, was calculated for each shoulder. Cuff integrity was
      evaluated by magnetic resonance imaging (116 cases) or computed arthrotomography
      scan (104 cases) at a mean 37 months' follow-up, and functional outcomes were
      evaluated with the Constant score. A recurrent tear was found in 79 cases (36%)
      and was more frequently encountered in posterosuperior tears. The likelihood of a
      recurrent tear was greater for tendons whose muscle showed fatty degeneration
      greater than grade 1. Fatty degeneration of the infraspinatus or subscapularis
      muscles had an influence on supraspinatus tendon outcome. A GFDI lower than 0.5
      was necessary to yield less than 25% retears. The mean global Constant score was
      75 at revision, significantly lower when a retear was present (70.5 versus 77.5).
      In the subgroup of watertight cuffs, it was lower when GFDI was higher. Fatty
      degeneration is an important prognostic factor in rotator cuff surgery.

PMID- 14671518
TI  - Pectoralis major transfer for serratus anterior paralysis.
AB  - Serratus anterior paralysis can result in winging of the scapula and weakness of
      arm elevation. The etiology of the condition is injury to the long thoracic
      nerve. There are many proposed causes of long thoracic nerve injury including
      acute trauma, Parsonage-Turner syndrome, or viral illness. The long length of the
      long thoracic nerve makes it prone to compression injury along the chest wall.
      Most patients recover nerve function with conservative treatment. In those in
      whom nerve function fails to recover, surgical treatment involving pectoralis
      major transfer may be beneficial. In this study 9 patients underwent pectoralis
      major transfer with a fascia lata extension graft. The symptoms of most were
      improved, with correction of the winging and improved movement in the affected
      shoulder.

PMID- 14671519
TI  - Scapulothoracic fusion for serratus anterior paralysis.
AB  - Paralysis of the serratus anterior may lead to severe disability. Many surgical
      options are available, from soft-tissue procedures to scapulothoracic fusion. We
      report the results of 10 consecutive scapulothoracic fusions in 10 patients (7
      men and 3 women) treated between 1980 and 1997. The mean age at surgery was 39
      years (range, 22-57 years). Paralysis of the serratus anterior was isolated in
      five patients. One patient was lost to follow-up, and one patient died from an
      unrelated cause. Fusion was not achieved in three patients, two of whom had
      successful revision within 1 year postoperatively. One patient with an excellent
      result had a traumatic arthrodesis fracture and underwent successful revision.
      Results were assessed in 8 patients, including 3 who had reoperation. At a mean
      follow-up of 6.2 years (range, 1-15 years), 6 patients had a very good or good
      result and returned to manual labor. The mean active mobility was limited to 93
      degrees in abduction and 101 degrees in forward elevation but was well tolerated.
      Two patients had a poor result because of nonunion and frozen shoulder,
      respectively. Scapulothoracic fusion may not be recommended as a primary
      procedure in the treatment of winging of the scapula due to serratus anterior
      paralysis. However, with the use of a careful technique, this method may be an
      alternative to muscle transfer, especially in patients in whom a previous soft
      tissue procedure has failed or in patients with strenuous activities or combined
      muscular lesions.

PMID- 14671520
TI  - Terrible triad of the shoulder.
AB  - The purpose of this study was to assess the functional outcome of the terrible
      triad of the shoulder, a rare combination of anterior shoulder dislocation,
      massive rotator cuff tear, and neurologic injury. Six patients with this
      condition have been treated at our institution since 1990. The mean age was 57
      years. All patients underwent rotator cuff repair (RCR). The mean time from
      injury to surgery was 5 months. Follow-up averaged 5.6 years. Functional outcome
      was recorded by use of the Shoulder Pain and Disability Index. Preoperative mean
      active forward elevation was 24 degrees, as compared with 98 degrees
      postoperatively. Strength improved from 3 lb to a mean of 12 lb in forward
      elevation and from 2 lb to 16 lb in external rotation. Clinically, 5 of 6
      patients achieved recovery of their nerve injury. Total Shoulder Pain and
      Disability Index postoperative scores revealed good or excellent results in 4 of
      6 patients. For this injury pattern, performing an RCR offers the patient the
      best chance for a favorable outcome. Waiting for neurologic recovery before
      performing RCR is not recommended.

PMID- 14671521
TI  - Outcomes of hemiarthroplasty for fractures of the proximal humerus.
AB  - We reviewed 80 shoulders (72 shoulders in 71 patients) treated with
      hemiarthroplasty. At follow-up, 66 patients (93%) were pain-free and satisfied
      with their results; the mean American Shoulder and Elbow Surgeons score was 76.6,
      the mean Simple Shoulder Test score was 7.5, the average forward flexion was 128
      degrees, external rotation was 43 degrees, and internal rotation was to L2.
      Radiographic analyses revealed nearly anatomic tuberosity reconstruction in 58
      shoulders, heterotopic ossification in 18, pseudosubluxation in 10, and superior
      migration in 15. Patients with superior migration had statistically lower mean
      American Shoulder and Elbow Surgeons scores, mean Simple Shoulder Test scores,
      and decreased forward flexion. Tuberosity complications occurred in 16 shoulders.
      Malunion of the greater tuberosity was the most common complication. Healing of
      the greater tuberosity more than 2 cm below the humeral head correlated with a
      worse functional result. Hemiarthroplasty for indicated fractures of the proximal
      humerus results in shoulder-level function and reproducible pain relief.

PMID- 14671522
TI  - Fixed-angle plate fixation in simulated fractures of the proximal humerus: a
      biomechanical study of a new device.
AB  - This study was performed to evaluate the biomechanical properties of a new device
      for displaced fractures of the proximal humerus. The device is a low-profile,
      fixed-angle plate specially designed for percutaneous application. With the use
      of embalmed cadaveric humeri, we simulated both noncomminuted and comminuted 2
      part surgical neck fractures of the proximal humerus. Each humerus of a pair was
      then randomly fixed with either the new experimental device or the Association
      for the Study of Internal Fixation (ASIF) T-plate and mechanically tested to
      failure in an axial shear-loading model. The two fixation devices were evaluated
      in paired humeri with regard to mode of failure, stiffness, displacement at
      physiologic loads, and displacement, load, and energy at the point of ultimate
      load before failure. In the noncomminuted fracture trials the experimental device
      exhibited significantly greater stiffness (P <.001; P =.002 for normalized
      values) and ultimate load before failure (P =.015) and significantly less
      displacement at higher physiologic loads (P =.031). In the comminuted fracture
      trials the experimental device exhibited significantly greater stiffness (P
      =.048), ultimate load (P <.001) and energy absorbed (P =.048) before failure, and
      significantly less displacement at higher (P =.004) and lower physiologic loads
      (P =.011). The study demonstrates improved biomechanical properties for the new
      experimental device over the T-plate in simulated fractures of the proximal
      humerus. We extrapolate that these improved biomechanical properties may prove
      advantageous in future clinical investigation.

PMID- 14671523
TI  - Clinical outcome of the treatment of floating shoulder by osteosynthesis for
      clavicular fracture alone.
AB  - Floating shoulder is an unstable combination of fractures that involve the
      scapular neck and the ipsilateral midclavicle and require surgical treatment. The
      clinical outcome of the surgical treatment of floating shoulder for the
      clavicular fracture alone is reported. In 5 male patients (mean age, 38.6 years),
      fixation of the clavicular fracture was achieved with the use of a bone plate in
      1 patient and with Kirschner wires in 4 patients. In all patients, union of the
      fractures of both the clavicle and the scapular neck was achieved, and the mean
      time for fracture healing was 17 weeks. According to the UCLA score, the mean
      score was 34.2 points during a mean follow-up period of 57.4 months. In patients
      with a floating shoulder, it is important to evaluate the severity of fracture
      displacement and coracoclavicular ligament rupture accurately, and on the basis
      of this evaluation, an appropriate treatment for both fractures that may lead to
      a satisfactory clinical outcome can be determined.

PMID- 14671524
TI  - A safe zone for resection of the medial end of the clavicle.
AB  - Medial clavicle resection is indicated when symptoms of sternoclavicular
      instability or degeneration remain disabling despite nonoperative management.
      Preservation or reconstruction of the costoclavicular ligament (rhomboid
      ligament) is essential to prevent subsequent instability of the remainder of the
      medial clavicle. Eighty-six cadaveric sternoclavicular joints were dissected to
      determine the distance (safe resection length [SRL]) from the inferior articular
      surface of the medial end of the clavicle to the most medial insertion of the
      costoclavicular ligament (rhomboid ligament). The mean SRL was 1.2 +/- 0.3 cm in
      men and 1.0 +/- 0.2 cm in women. Resection of 1.0 cm of the medial clavicle would
      result in no or minimal disruption of the costoclavicular ligament in 84% of men,
      and resection of 0.9 cm of the medial clavicle would result in no or minimal
      disruption of the costoclavicular ligament in 89% of women. We recommend that
      these amounts be used as a guide to safe resection of the medial clavicle but
      that the costoclavicular ligament be exposed to allow certainty of preservation.

PMID- 14671525
TI  - A cadaveric study examining acromioclavicular joint congruity after different
      methods of coracoclavicular loop repair.
AB  - A basic principle in the treatment of joint injuries is to restore congruity with
      the hope that restoration may lessen the incidence of late arthritis. The
      acromioclavicular (AC) joint is frequently injured. Many AC joint injuries are
      treated nonoperatively; others are treated surgically. Coracoclavicular loop
      repair of the AC joint is believed to lead to anterior displacement of the
      clavicle relative to the acromion. This cadaveric study evaluated the
      effectiveness of three techniques of coracoclavicular loop repair in restoring AC
      joint congruity through measurement of anterior displacement. Fourteen shoulders
      were repaired by the three different techniques, all of which consisted of
      fixation through a drill hole in the clavicle and around the crook of the
      coracoid with a suture. The techniques only varied by the placement of the drill
      hole in the clavicle (ie, either posterior, middle, or anterior). The results of
      this study indicate that as the drill hole moved anteriorly on the clavicle,
      joint congruity was more closely approached and less anterior displacement of the
      clavicle occurred. However, none of the methods of coracoclavicular loop fixation
      restored full AC joint congruity.

PMID- 14671526
TI  - Grade I and II acromioclavicular dislocations: results of conservative treatment.
AB  - The purpose of this study was to assess the results of acute grade I and II
      acromioclavicular (AC) joint sprains treated by conservative measures. Between
      1993 and 1997, 37 consecutive patients were treated conservatively for AC joint
      sprains, grade I and II in the Tossy classification. Of these patients, 4 were
      excluded (three lost to follow-up and one sustained a further AC injury), leaving
      a series of 33 patients. Among them, in 9 (27%), chronic AC joint pathology that
      required subsequent surgery developed at a mean of 26 months after injury. The
      remaining 24 were reviewed clinically and radiologically at a mean of 6.3 years
      (range, 4-8 years) after injury. At the latest follow-up, 17 of the 33 patients
      (52%) remained asymptomatic. Of the 24 patients reviewed, 7 complained of
      activity-related pain. Eight patients presented with residual anteroposterior
      instability. Tenderness at the AC joint as well as a positive cross-body test was
      observed in 12 patients. The mean Constant score at follow-up was 82 points. The
      x-ray films showed degenerative changes in 13 patients, ossification of the
      coracoclavicular ligaments in 2, an association of degenerative changes with
      ossification of the coracoclavicular ligaments in 3, and distal clavicular
      osteolysis in 3. Only 4 cases had no radiographic changes after this kind of AC
      injury. On the basis of these results, we conclude that the severity of the
      consequences after grade I and II AC sprains is underestimated.

PMID- 14671527
TI  - Surgical technique for supracondylar fracture of the humerus with percutaneous
      leverage pinning.
AB  - Percutaneous pinning with a leverage technique for supracondylar fracture of the
      humerus was performed in 36 elbows in 35 children. The patient was placed in the
      lateral position with the forearm hanging. Under radiographic imaging, a
      Kirschner wire, as a reduction pin, was inserted into the fracture line from the
      dorsal side, passed through the posterior cortex of the proximal fragment, and
      turned distally. After reduction of the posterior displacement by the leverage
      technique, the reduction pin was driven into the anterior cortex of the proximal
      fragment. Subsequently, a Kirschner wire was inserted from the lateral condyle
      for fixation between the proximal and distal fragments. This percutaneous pinning
      technique was successfully performed in 32 of 36 elbows, with excellent
      functional results in 28 elbows and good results in 4, as well as excellent
      cosmetic results in 27 elbows and good results in 5, based on the evaluation
      criteria of Flynn et al.

PMID- 14671528
TI  - Rupture of the distal biceps brachii tendon: isokinetic power analysis and
      complications after anatomic reinsertion compared with fixation to the brachialis
      muscle.
AB  - Anatomic reattachment of the distal biceps tendon is well established but bears
      the risk of complications including loss of motion and nerve damage. We
      questioned whether nonanatomic repair by tenodesis to the brachialis muscle is
      able to accomplish similar results with less risk. We compared the results of
      anatomic repair with suture anchors (n = 6) with the results of nonanatomic
      repair (n = 8). Anatomic reattachment of the biceps tendon can restore full power
      of flexion in most cases as determined by isokinetic muscle tests (mean, 96.8%
      compared with the contralateral side). Nonanatomic repair also restores flexion
      strength to a mean of 96%. Supination power averaged 91% after anatomic repair.
      Supination strength after nonanatomic repair did not improve in 4 of 8 patients
      (42%-56% of the uninjured arm). The other 4 patients were able to produce 80% to
      150% of the strength of the contralateral side. Major complications such as
      radioulnar synostosis or motor nerve damage were not encountered in either group.
      Heterotopic ossification was seen in 4 cases after reinsertion to the tuberosity.
      One of these patients was not satisfied with the procedure because of anterior
      elbow pain, even at rest. After tenodesis to the brachialis, one patient was
      unsatisfied because of considerable weakness. We concluded that major
      complications after anatomic repair are rare but must not be ignored. Tenodesis
      of the distal biceps tendon is a safe alternative procedure. We inform our
      patients about the benefits and risks of anatomic and nonanatomic repair as well
      as those of nonoperative treatment. The decision concerning the type of therapy
      best suited for an individual patient should be made on an informed consent
      basis.

PMID- 14671529
TI  - Mechanical environment of the supraspinatus tendon: a two-dimensional finite
      element model analysis.
AB  - We performed 2-dimensional finite element model analysis to estimate the
      mechanical environment of the supraspinatus tendon. The geometric shape of the
      finite element model was determined by magnetic resonance imaging of a normal
      human shoulder obtained at 0 degrees, 30 degrees, and 60 degrees of abduction,
      whereas the histologic location of noncalcified and calcified fibrocartilage was
      determined from a cadaveric specimen. The supraspinatus tendon was pulled
      proximally with the force of 10 N at 0 degrees, 53 N at 30 degrees, and 115 N at
      60 degrees of abduction. The area of high principal stress maximum was observed
      on the articular side of the supraspinatus tendon, which shifted toward the
      insertion as the arm was abducted. High stress concentration on the articular
      side of the supraspinatus tendon near its insertion during arm elevation may
      explain the frequent occurrence of rotator cuff tears at this site.

PMID- 14671530
TI  - Evaluation of an anesthetic pump for postoperative care after shoulder surgery.
AB  - In theory, a prolonged, local infusion of anesthetic into a surgical field should
      reduce postoperative pain. Recently, disposable products have become available to
      implement this, but the balance between cost and benefit is controversial. This
      study evaluated such a device in two specific types of arthroscopic surgery of
      the shoulder: decompression of the subacromial space and repair of a torn labrum
      in the glenohumeral joint. Placement of the catheter into the glenohumeral joint
      resulted in problems in removing the device from some cases so that application
      is not recommended. When the catheter was placed in the subacromial space, the
      infusion pump was associated with significantly shorter stays in the recovery
      room, but there was no benefit over placebo with regard to pain, demand for
      rescue narcotic, or recovery of motion. Furthermore, use of the device presented
      some inconveniences to the surgical staff and the patient. It was concluded that
      use of this particular device in these particular applications is not justified.

PMID- 14671531
TI  - The measurement of normative American Shoulder and Elbow Surgeons scores.
AB  - We determined baseline scores on the American Shoulder and Elbow Surgeons (ASES)
      questionnaire in individuals who had no known shoulder condition and evaluated
      related factors that could influence the score. A modified version of the
      questionnaire was completed by 343 patients from an outpatient orthopaedic center
      being seen for conditions unrelated to the shoulder. A separate group completed
      the questionnaire at two different times to assess its reliability. The mean ASES
      score was 92.2 +/- 14.5 points. The instrument was found to be very reliable
      (intraclass correlation coefficient = 0.96). Only the variables of shoulder
      status and sports participation entered the regression model to explain the
      variance in scores. Subjects aged 60 years or older exhibited decreased ability
      to lift above shoulder level and reach behind the back when compared with younger
      cohorts. Previous investigators have made the assumption that a normal preinjury
      ASES score is 100 points. This study raises questions about this assumption. This
      information can serve as a basis to compare normative scores with those of
      patients with active shoulder disease.

PMID- 14671532
TI  - Warning: pulmonary embolism can occur after elective shoulder surgery-report of
      two cases and survey of the members of the American Shoulder and Elbow Surgeons.

PMID- 14671533
TI  - Nonunion of a humeral shaft fracture after unrecognized longstanding posterior
      shoulder dislocation.

PMID- 14671534
TI  - Fatigue failure of a shoulder hemiarthroplasty stem: a case report.

PMID- 14671535
TI  - Entrapment of the ulnar nerve in heterotopic ossification of the elbow: a case
      report.

PMID- 14671536
TI  - Isolated fractures of the greater tuberosity of the proximal humerus.
AB  - This review addresses isolated greater tuberosity fractures of the proximal
      humerus. The important aspects of the epidemiology, anatomy, fracture
      classification, associated injuries, and treatment are discussed. Although
      isolated greater tuberosity fractures are well recognized, there are few studies
      that specifically evaluate the outcome of these injuries. Our experience and
      review of the recent literature suggest that more precise evaluation of
      diagnostic criteria, treatment selection, and outcome is required.

PMID- 14671537
TI  - [Treatment of gunshot wounds of the veins in the first echelon of specialized
      surgical care].
AB  - Results of first specialized aid to 26 wounded with injuries of the major veins
      are analyzed. Rate and nature of injuries of various major veins are regarded.
      Complete rupture of the vessel and its destruction with dehiscence of different
      length were seen in more than half of the cases (57.7%). In this case repair of
      venous vessel patency required various plastic methods. In lateral or incomplete
      transverse rupture it was possible to put lateral or circular vascular suture.
      Ligature of injured venous vessel was performed in half of the cases. Based on
      anatomic features of venous circulation in the extremities, immediate and long
      term results of the treatment, 2 groups of injuries were identified: 1st -
      ligature of the veins did not lead to disorders of venous circulation and
      function of the extremity in the nearest and long-term period after surgery; 2nd 
      ligature of the vessel was dangerous due to serious disorders of venous
      circulation in the nearest period after surgery and might lead to disorders of
      extremity function and disability. In gunshot wounds of the major veins good
      results may be achieved in early reconstructive surgeries with individual
      approach allowing for general condition of the wounded and nature of vessel
      injury.

PMID- 14671538
TI  - [Reconstructive surgery on the femoro-popliteal segment in combination with
      lumbar sympathectomy].
AB  - Long-term results of 660 reconstructive surgeries on the arteries of the femoro
      popliteal segment performed from 1975 to 2002 are analyzed. Two hundred and
      twenty-eight (34.5%) of them were combined with lumbar sympathectomy (LSE) on the
      affected side. It was demonstrated that LSE influences outcomes of
      reconstructions on the femoro-popliteal segment. This influence depends on a
      primary degree of leg ischemia. At the stage of intermittent claudication LSE
      permits to improve patency of the femoro-popliteal segment, salvage of the leg,
      to decrease the rate of postoperative complications due to reduction of
      thrombosis and purulation rates. The rate of cardiovascular complications
      increases. In critical limb ischemia effect of LSE is opposite. It increases the
      rate of repeated occlusions and amputations compared with reconstructive
      surgeries without LSE. The rate of postoperative complications also increased due
      to thrombosis and cardiovascular complications. It is concluded that LSE is the
      factor improving outcomes of reconstructive surgery on the femoro-popliteal
      segment, but it must be used differentially. It is necessary to perform LSE
      during all reconstructive surgeries in patients with intermittent claudication
      and without serious cardiovascular diseases. In critical limb ischemia and
      serious concomitant cardiovascular diseases LSE must be avoided.

PMID- 14671539
TI  - [Quality of life in surgical treatment of varicose disease].
AB  - A decrease of surgical trauma and improvement of anesthesia quality are the key
      points in quality life improvement after surgical treatment of varicose disease.
      Two variants of incisions were used: mini approaches of length not more than 20
      mm and micro approaches of length to 2 - 3 mm. During surgery instruments of
      decreased sizes were applied. Direct and distant mini approaches were used for
      crossectomy. Disjunction of Coccett's perforated veins in trophic disorders was
      performed through distant mini approach, valvuloplasty of the femoral vein -
      through two mini approaches. Removal of subcutaneous and communicated veins was
      performed through few micro approaches. One hundred and seventy-four patients
      with various forms of varicose disease underwent surgery under combined (general 
      fentanil, sibazon, propofol and local - lidocain, novocain) anesthesia. Total
      length of cutaneous incisions ranged from 15 to 85 mm. Fast achievement of
      primary state after surgery and complete recovery during first week was seen.
      High index of quality of life both in the surgery day and nearest days after it
      was noted.

PMID- 14671540
TI  - [Surgical treatment of combined burn strictures of the esophagus and the
      stomach].
AB  - Experience in treatment of 168 patients with burns of the esophagus including 42
      (25%) with consequences of combined chemical burns of the esophagus and the
      stomach is presented. In combined burn strictures of the esophagus and a
      pyloroantral part of the stomach with a large area of the lesion the method of
      repair of enteral alimentation was successfully applied. This method lies in
      creation of distal ended gastrostoma on the anterior wall of the stomach with
      gastroenterostomy by Roux. Low traumaticity, simplicity and reliability of
      gastrostoma healing are the advantages of this method. There were no
      complications after ended gastrostoma creation.

PMID- 14671541
TI  - [Laser doppler flowmetry for assessment of acute pancreatitis treatment
      efficacy].
AB  - Microcirculation was studied with laser doppler flowmetry in 226 patients with
      acute destructive pancreatitis treated with standard detoxication,
      antiinflammatory, antibacterial and surgical methods. The examination was
      performed on the unit LAKK-01 (NPP 'Lazma', Russia) by original methods based on
      the study of microcirculation in biologically active points. Based on analysis of
      2500 dopplerograms, criteria of assessment of organic and systemic capillary
      circulation and also laser doppler flowmetric characteristics of 4 degree
      microcirculation's insufficiency were developed. The proposed scheme was
      effectively applied for assessment of each medical procedure and of all curative
      complex in general.

PMID- 14671542
TI  - [Importance of morphofunctional condition of endocrine cells of gastric mucosa in
      prognosis of ulcer disease complications].
AB  - Problems of morphofunctional condition of endocrine cells of gastric mucosa and
      their importance in prognosis of ulcer disease complications are discussed. Sixty
      patients with various complications of ulcer disease were examined. Investigation
      of quantity and functional activity of 4 most frequent types of gastric mucosa
      endocrine cells in different zones of affected area permitted to reveal strong
      correlation between quantity and functional activity of these cells. Changes of
      endocrine cells are reliable and have high prognostic significance in development
      of ulcer disease complications and must be taken into account by physicians to
      select right policy for prevention of these complications.

PMID- 14671543
TI  - [Laparoscopy in the treatment of intestinal invagination in children].
AB  - The experience with laparoscopy in diagnosis and treatment of intestinal
      invagination in 142 children aged from 2 months to 11 years (study group) is
      reviewed. Endoscopic desinvagination was performed when conservative
      (pneumoirrhigoscopy) treatment was ineffective or hospitalization of patients was
      late. The invaginate was straightened out under video-control with two atraumatic
      forceps-graspers introduced into abdominal cavity and simultaneous pumping of air
      into the large intestine. This method permitted to cure completely intestinal
      invagination in 126 (88.7%) patients without laparotomy. In the control group (50
      children aged from 3 months to 2 years) traditional surgery (laparotomy) was
      performed. Mean time of laparoscopic desinvagination was 32.6 min, time of
      surgery in the control group - 65 min. Postoperative complications in the study
      group were 5 times more rare than in the control. Mean time of hospitalization in
      the study group was decreased 3 times compared with the control. There were no
      lethal outcomes in both groups. Laparoscopic desinvagination is safe and high
      effective procedure in the treatment of intestinal invagination in children.

PMID- 14671544
TI  - [Microbiologic characteristics of wound infectious process in use of ion-exchange
      sorbents].
AB  - In Wistar rats with modified Danilina's method a purulent wound was simulated.
      The animals were divided into 5 groups of treatment. In the study groups
      applications on the wound of ion-exchange sorbents of natural origin (ceolyt
      including its modification with 1% silver, multicomponent ointment with bentonit,
      poviargol, propolis and metronidazol) were used. In the control groups gauze
      bandages and polyethylenoxyde were applied. When modified ceolyt and the ointment
      were used, earlier reduction of general contamination lower to critical level was
      seen. Ceolyt modified with silver demonstrated higher antimicrobic effect on
      gramnegative microflora compared with ointment composition. Ceolyt and its
      silvered modification were studied in vitro. Zones of growth absence were
      detected in places of application of silvered ceolyt that testifies to
      antimicrobic activity of silvered composition.

PMID- 14671545
TI  - [Monitoring of incidence of perforative ulcers in Belarus].
AB  - The rate of perforative gastroduodenal ulcers in Belarus over 1960 - 2001 was
      analyzed. Before 1990-ties insignificant tendency to increase was seen. There was
      no reaction to Chernobyl accident in 1986. In the first half of 1990 ies a
      significant (almost 2 times) increase of perforative ulcers rate was seen. These
      changes coincided with break-up of USSR and decrease of material level of life.
      Social and economic factors dominated in risk of ulcer disease complications,
      perforation, in particular. It is necessary to increase the role of
      dispensarization and elective surgery in patients with a severe course of ulcer
      disease.

PMID- 14671546
TI  - [The use of fatty acid beta-oxidation inhibitor mildronate as monotherapy or in
      combination with atenolol in patients with left ventricular dysfunction after
      myocardial infarction].
AB  - AIM: To assess antiischemic efficacy, safety and effect on myocardial perfusion
      of a course treatment with mildronate (as monotherapy and in combination with
      atenolol) in patients with postinfarction left ventricular dysfunction associated
      with moderate heart failure. MATERIAL AND METHODS: Patients (n=47) with
      postinfarction cardiosclerosis, angina, and decreased tolerance to physical
      exertion were divided into 2 groups. Patients of group 1 had functional class II
      angina and NYHA class I-II heart failure, patients of group 2 had functional
      class II-III angina and severe heart failure. Mildronate (0.75-1.0 g/day) was
      used as monotherapy in group 1 and in combination with atenolol (25-50 mg/day) in
      group 2. Duration of therapy was 3 weeks. RESULTS AND CONCLUSION: The use of
      mildronate was associated with marked antiischemic effect. Combined
      administration of mildronate and atenolol resulted in additional antiischemic
      effect without impairment of hemodynamics in patients with severe heart failure.
      Course use of mildronate was well tolerated. Adverse effects were registered in
      4,2% of cases.

PMID- 14671547
TI  - [Left ventricular remodeling in chronic heart failure: clinical-morphological
      parallels].
AB  - AIM: To study morphofunctional state of left ventricular and right atrial
      myocardium in chronic heart failure at tissue, cellular and subcellular levels
      and to assess relationship between observed morphological changes and
      echocardiographical characteristics of left ventricular remodeling. RESULTS AND
      CONCLUSION: Myocardial remodeling in chronic heart failure was characterized by
      impaired cellular-stromal balance, enhanced processes of degeneration of
      cardiomyocytes, lowered energy availability in these cells, and insufficient
      intracellular regeneration. Fairly close relationship was observed between
      morphological myocardial changes and echocardiographical parameters of left
      ventricular remodeling.

PMID- 14671548
TI  - [Register of acute coronary syndromes in Russia: treatment and in hospital
      outcomes in non-ST elevation acute coronary syndrome].
AB  - Data from about 50 consecutive patients with acute coronary syndromes aged > or
      =18 years admitted to 59 hospitals in different Russian cities were collected
      between November 2000 and July 2001. In addition to presumably ischemic symptoms
      within previous 24 hours they were to have ischemic ECG changes, documented
      coronary heart disease or positive markers of myocardial necrosis. Of 2806
      patients included into registry 1394 (49.7%) had non-ST elevation acute coronary
      syndrome. Markers of myocardial necrosis (mainly CK activity) were evaluated in
      59.5% of them. Frequency of interventions known to improve outcome was rather
      low: aspirin in acute phase was used in 73% (contraindications were reported just
      in 6%), thyenopyridines - in few cases, unfractionated heparin intravenously only
      with APTT control - in 11.8%, low-molecular weight heparins - in 7.4% of
      patients. Beta-blockers were prescribed in 55.6% of cases (with fist dose
      intravenously in 2.9%). Lipid lowering drugs were recommended on discharge to 15%
      of patients (to 20% with known hypercholesterolemia). Coronary angiography and
      revascularization procedures were performed in 25 (1.8%) and 11 (0.8%) patients,
      respectively. However hospital mortality appeared to be relatively low (3.8%).
      Meanwhile rates of (re)infactions and angina recurrences during hospitalization
      were high - 16.5 and 25.1% of cases, respectively.

PMID- 14671549
TI  - [The effect of risk factors on development of myocardial infarction among
      professional drivers in Kaunas].
AB  - We investigated effect of risk factors on elevated first myocardial infarction
      risk among professional drivers. We carried out case-control study among men aged
      25-64 years in Kaunas in 1997-2000. We identified myocardial infarction cases
      (n=448) from the myocardial infarction hospital register (International
      Classification of Diseases, 10-th revision, code 121). Controls (n=1777) were
      selected on the basis of age, gender and city district of residence. We obtained
      information on sociodemographic, psychosocial and behavioral factors. We used the
      International Standard Classification of Occupations (ISCO) to code for
      occupations and conducted logistic regression analysis to evaluate association of
      risk factors with myocardial infarction in professional drivers. Compared with
      other occupations being a professional driver was associated with increased risk
      of first myocardial infarction with odds ratio (OR) adjusted for smoking,
      hypertension, presence of stress, obesity and educational status 1.42 and 95%
      confidence intervals (CI) 1.06-1.90. However additional adjustment for exposure
      to occupational vibration for 20 years or more eliminated effect of this
      occupation (OR 0.96, 95%CI 0.67-1.37). Among drivers exposure to occupational
      vibration for > or =20 years was most closely related to myocardial infarction
      (OR 3.01, 95% CI 1.54-5.89), while hypertension was associated with OR 2.80 (95%
      CI 1.58-4.96).

PMID- 14671550
TI  - [Pathomorphological features of atherosclerotic plaques in acute coronary
      syndrome].
AB  - We studied transverse cross-sections (5 mm apart) of coronary arteries of 45 men
      and women who died of acute myocardial infarction at the age of 41-79 years. Both
      stable and unstable atherosclerotic plaques were found in all cases. Stable
      plaques consisted of solid fibrous tissue with small amount of lipids and
      cellular elements. Unstable plaques were represented by 2 types: lipid (75.6%)
      and dystrophic necrotic (24.4%). Various degree of inflammatory cellular reaction
      was present in all lipid plaques. Factors associated with fibrous cap rupture
      were identified. Lipid plaques were more frequent in subjects with elevated while
      dystrophic-necrotic - with normal levels of blood lipids (measured during life).

PMID- 14671551
TI  - [The state of hemodynamics and microcirculation in patients with hypertensive
      disease during long term controlled therapy with lisinopril].
AB  - Lisinopril (Diroton, 10-40 mg/day) was given for 6 months to 30 patients (mean
      age 57.2+/-0.64 years) with stage II hypertension (WHO, 1999). Left ventricular
      diastolic function and microcirculation were assessed by echocardiography and
      biomicroscopy, respectively. Treatment with lisinopril was associated with
      improvements of impaired left ventricular diastolic function, structural and
      functional state of the heart. Parameters of microcirculatory vascular bed also
      improved.

PMID- 14671552
TI  - [Inpatient cardiac defibrillation: efficacy of bipolar sinusoidal impulse].
AB  - Efficacy of external defibrillation of the heart with low energy (</=65-195 J)
      bipolar quasi sinusoidal discharges was studied in 76 patients with induced,
      primary (overall 70 episodes), and secondary (88 episodes) ventricular
      fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) with
      or without acute myocardial infarction. Maximal effective discharge energy used
      for termination of induced and primary VF or VT was 90 J in 10 of 66 patients
      (15%) ). Meanwhile discharge energy 165-193 J was required for termination of
      secondary VF in 6 of 34 patients (18%). Overall efficacy of cardiac
      defibrillation with discharge energies </=115 and </=193 J was 92 and 100%,
      respectively. Success of resuscitation in patients with prolonged (2-28 min)
      primary and secondary VF was 82 and 68%, respectively. VF duration before first
      discharge (0,5-8 min) did not affect significantly magnitude of effective energy
      in interval between 90 and 193 J. However lower energy discharges were less
      effective when duration of fibrillation exceeded 30 sec.

PMID- 14671553
TI  - [Effect of radio frequency catheter ablation on spectral parameters of heart rate
      variability in patients with paroxysmal supraventricular tachyarrhythmias].
AB  - AIM: To assess effect of radio frequency catheter ablation (RFCA) on heart rate
      variability (HRV) in patients with supraventricular tachyarrhythmias (SVT).
      METHODS: Spectral analysis of HRV on 5-minute ECG strips was carried out in 19
      patients with SVT before and 2 days after RFCA. RESULTS: Both total and high
      frequency power significantly decreased (p<0,05) after RFCA in supine and
      orthostatic positions. Significant decrease of low frequency power occurred after
      RFCA in orthostatic position. CONCLUSION: In patients with SVT RFCA alters
      autonomic regulation of chronotropic function of the heart. Sympathetic and
      parasympathetic influences on the chronotropic function of the heart are
      attenuated in early period after the procedure.

PMID- 14671554
TI  - [Effects of Na(+)/H(+)-exchanger inhibition on metabolism of area at risk and
      myocardial infarct size in dogs].
AB  - The aim of this work was to study cardioprotective effects of BIIB 722, a novel
      Na(+)/H(+) exchanger-1 inhibitor, during regional ischemia and reperfusion in
      canine myocardium. The experiments were carried out on anaesthetized dogs
      intubated and artificially ventilated with room air enriched with oxygen.
      Regional ischemia was induced by 30-min occlusion of a diagonal branch of left
      anterior descending coronary artery (LAD), which was followed by 60-min
      reperfusion. BIIB 722, dissolved in 280 mM xylitol, was infused intracoronary for
      10 min prior to LAD occlusion and at the beginning of reperfusion at the rate of
      1 ml/min (30 microg/g myocardial tissue). In the control group, 280 mM xylitol
      was used for intracoronary administration with the same regimen. Microdialysis
      probes were implanted in the region of LAD occlusion to monitor interstitial pH,
      inorganic phosphate (Pi) and hydroxyl radical adduct. Energy state of the area at
      risk was evaluated by ATP and phosphocreatine (PCr) contents, cell membrane
      damage was assessed by total creatine (SigmaCr=PCr+Cr) tissue content. Myocardial
      infarct size was determined by staining with Evans Blue dye and further
      incubation of left ventricular slices in 2,3,5-triphenyltetrazolium chloride. The
      percentage ratio of infarct size to area at risk was calculated by computer
      planimetry. BIIB 722 administration had no effect on cardiac hemodynamics and
      acid-base indices of arterial blood throughout the experiments but induced 1.8
      fold reduction of myocardial infarct size comparing with control. Treatment with
      BIIB 722 decreased acidification of the interstitial fluid following ischemia and
      facilitated recovery of pH to initial value on reperfusion. This effect was
      combined with significantly less Pi formation in the area at risk during LAD
      occlusion and reduction of this index to the initial value during reperfusion. At
      the end of reperfusion, the treated group showed augmented recovery of ATP and
      PCr tissue levels and higher content of SigmaCr comparing with the control.
      Additionally, BIIB 722 treatment markedly decreased generation of free oxygen
      radicals following LAD occlusion and completely avoided their formation on early
      reperfusion. The results indicate that BIIB 722 ability to limit myocardial
      infarct size in dogs is tightly connected with its influence on energy metabolism
      and oxygen radical generation.

PMID- 14671555
TI  - [Genetic predictors of left ventricular hypertrophy: do polymorphisms of
      peroxisome proliferator activated nuclear receptor genes play any role?].
AB  - AIM: To assess possible associations of polymorphic markers of PPARA and PPARG2
      genes with presence of left ventricular hypertrophy (LVH) in patients with
      hypertension. MATERIAL: Patients with hypertension (n=163, mean age 60.93+/-0.82
      years) with (n=110) and without (n=53) LVH. METHODS: Echocardiography was used
      for evaluation of left ventricular mass and mass index and polymerase chain
      reaction - for identification of alleles and genotypes of polymorphic markers of
      ACE, NOS3, PPARA, PPARG2 genes. RESULTS AND CONCLUSION: There was no association
      between presence of LVH and polymorphic marker Pro12AIa. Carriers of 4a allele of
      a polymorphic marker ecNOS4a/4b of NOS3 gene, A allale of a polymorphic marker
      G7831A of ACE gene, and C allele of PPARA gene had significantly greater left
      ventricular myocardial mass index. Monofactorial regression analysis showed that
      degree of LVH was significantly related to age, duration of hypertension, maximal
      systolic blood pressure. No relationship was found between left ventricular mass
      index and smoking, maximal diastolic blood pressure, habitual systolic and
      diastolic blood pressure, duration of hypertension, presence of ischemic heart
      disease, diabetes. According to results of multifactorial analysis A allele of a
      polymorphic marker G7831A of ACE gene, age and maximal systolic blood pressure
      were while C allele of PPARA gene was not independently related to the presence
      of LVH.

PMID- 14671556
TI  - [Role of Chlamydia, mycoplasma and cytomegalovirus infection in the development
      of coronary artery disease].
AB  - AIM: To assess relationship between some infection factors and presence of
      coronary heart disease. MATERIAL: Patients with myocardial infarction (n=56),
      unstable angina (n=50), stable angina (n=50) and age - matched controls (n=49).
      METHODS: Levels of IgG, IgM, IgA antibodies to Chlamydia pneumonia, Chlamydia
      trachomatis, Chlamydia psittaci, IgG, IgM antibodies to Cytomegalovirus, and also
      of antibodies and antigen to Mycoplasma pneumoniae were measured in blood serum.
      RESULTS: Compared with controls patients with coronary heart disease had higher
      frequency of seropositivity to Chlamydia pneumonia, Mycoplasma pneumonia and
      Cytomegalovirus (p< 0.05 ) and similar levels of seropositivity to Chlamydia
      trachomatis and Chlamydia psittaci. Infectious burden (quantity of antibodies per
      one patient) was significantly higher in patients with myocardial infarction,
      unstable and stable angina than in controls (1.58, 1.42, 1.41 and 0.95,
      respectively). CONCLUSION: Our results confirm presence of association between
      infection and coronary heart disease.

PMID- 14671557
TI  - [Stress echocardiography with the use of impulse wave tissue Doppler technology
      in diagnosis and quantitative evaluation of concealed myocardial ischemia].
AB  - AIM: To elucidate the role of the use of impulse-wave tissue doppler technology
      during stress echocardiography with transesophageal atrial pacing for diagnosis
      and evaluation of concealed myocardial ischemia. MATERIAL: Patients (n=82, 72
      men, 10 women, mean age 43+/-10 years) with syndrome of cardiac pain of obscure
      etiology. METHODS: Regional contractility of left ventricular wall was studied
      through apical approach with the use of 12-segment model. Peak systolic velocity
      of myocardial segments (S, cm/s), its acceleration (Asl, cm/s(2)), duration of
      period of preejection (PEP, ms) and isovolumic relaxation time (IVRT, ms) of each
      segment were calculated at rest, and during subthreshold and threshold pacing.
      RESULTS: Concealed myocardial ischemia was revealed by stress echo in 44
      patients. Total number of analyzed segments was 984 and parameters of impulse
      wave tissue doppler could be measured in 959 (97%) segments. At peak pacing rate
      during stress test 789 (82%) segments were normokinetic, 142 (15%) - hypokinetic,
      20 (2%) - akinetic, and 8 (1%) - dyskinetic. Absence of increase or decrease of S
      and prolongation of PEP by 10% or more from baseline during stress test were
      found to be predictors of myocardial ischemia (sensitivity 35 and 75%,
      respectively, specificity 37 and 81%, respectively), and criteria of
      objectification of zones of left ventricular wall with impaired contractility
      (sensitivity 51 and 75%, respectively, specificity 52 and 76%, respectively).
      During stress echocardiography only dynamics of myocardial IVRT reflected the
      state of regional left ventricular diastolic function. CONCLUSION: Stress
      echocardiography with transesophageal atrial pacing combined with impulse-wave
      tissue doppler imaging is a highly informative method of diagnosis and
      quantitative assessment of concealed myocardial ischemia.

PMID- 14671558
TI  - [Results of pharmacoepidemiological study of arterial hypertension in Russia
      (PIFAGOR)].
AB  - AIM: To assess physicians preferences concerning the use of various groups of
      antihypertensive drugs in Russia. METHODS: Special questionnaires containing 8
      questions related to preferential adherence to representatives of various groups
      of antihypertensive drugs were distributed among practicing physicians who
      routinely treated patients with hypertension. RESULTS: Of questionnaires returned
      between January and July of 2002 from 34 towns 530 were considered valid for
      analysis. Half of responses (50.4%) were from hospital physicians, 40.5% - from
      physicians of policlinics (outpatient clinics), 9.1% - from physicians working in
      other health care facilities. Most of respondents were internists (60.8%) and
      cardiologists (32.7%). Preferences concerning prescription of antihypertensive
      drugs were distributed in the following way: angiotensin converting enzyme
      inhibitors - 32% (50% captopril and enalapril); beta-adrenoblockers - 27% (77%
      atenolol, metoprolol and propranolol); diuretics (hydrochlorothiazide and
      indapamide) - 22%; calcium antagonists - 15% (81% verapamil, nifedipine,
      diltiazem, 64% - long acting preparations); angiotensin receptor blockers - 1.7%;
      centrally acting drugs - 1.5%; alpha-adrenoblockers - 0.8%. CONCLUSION:
      Tendencies in real life treatment of patients with hypertension in Russia should
      be considered positive. Basic antihypertensive therapy included agents (mostly
      long-acting) from 4 main classes and the use of outdated drugs such as clonidine
      and reserpine was low.

PMID- 14671559
TI  - [Distribution of blood pressure levels and prevalence of hypertension among adult
      population of Tomsk].
AB  - Cross-sectional study of distribution of blood pressure levels and prevalence of
      hypertension among adult 25-64 year old nonorganized population of Tomsk revealed
      unfavorable epidemiological situation and stressed necessity of implementation of
      populational strategy of prevention of hypertension.

PMID- 14671560
TI  - [Hyperplasia and degranulation of mast cells in intima of the aorta and pulmonary
      artery in acute myocardial infarction].
AB  - AIM: To study morphological and functional state of mast cells from intima of the
      aorta and pulmonary artery associated with acute cardiovascular failure due to
      myocardial infarction. MATERIAL: Vessels of 44 men who died of acute myocardial
      infarction at the age of 42-73 years. METHODS: Intimal cellular elements were
      analyzed in membranous preparations of intima and transverse cross-sections of
      vessels. Parameters studied were density of mast cells (number per unit of intima
      area), percent of mast cells in the state of degranulation, degree of
      polymorphism of mast cells. Data obtained in victims of myocardial infarctions
      were compared with those from apparently healthy persons who died of accidental
      causes. RESULTS: Intima of both the aorta and pulmonary artery in all cases of
      myocardial infarction was characterized by: 1. hyperplasia of mast cells (44.9
      cells/mm(2) compared with 9.6 in controls); 2. substantially increased number of
      cells in the state of secretory activity (36.9 cells/mm(2) compared with 4.0 in
      controls); 3. pronounced polymorphism of mast cells reflecting disturbed balance
      between processes of degranulation and regranulation. Increased number of mast
      cells in intima was accompanied by elevated content of various T-lymphocytes and
      monocytes. Changes of mast cell population in main vessels of the body observed
      in this study can be considered as reaction aimed at stabilization of circulation
      in acute myocardial infarction.

PMID- 14671561
TI  - [Salt consumption and arterial hypertension].
AB  - Solution of the problem of hypertension lies in prevention. And here it is
      impossible to get along without risk factor concept. Most valuable risk factor
      for development of hypertension is salt - sodium ion at first hand. Increased
      salt intake with diet modifies effect of such important risk factors of
      hypertension as aggravated heredity, excessive body mass, low physical activity,
      alcohol, etc. Thus heredity can be realized through decreased sensitivity of
      taste receptors of the tongue causing involuntary excessive sodium consumption.
      The authors believe that it is restriction of salt intake that will make
      prevention of hypertension feasible.

PMID- 14671562
TI  - [Peroxisome proliferator activated nuclear receptors: possible role in the
      development of atherosclerosis].
AB  - Peroxisome proliferator activated nuclear receptors (PPAR) belong to steroid
      receptors and are represented by 3 types: PPAR alpha, PPAR beta, PPAR gamma. PPAR
      alpha is a key regulator of fatty acid beta-oxidation, participates in
      development of inflammatory reaction and atherosclerosis formation. Main effects
      of fibrates are mediated through PPAR alpha activation. PPAR gamma plays
      important role in lipid metabolism, processes of cell differentiation and growth,
      participates in glucose utilization and mechanisms of insulin resistance.
      Specific activators of PPAR gamma are glytazones--a group of antidiabetic drugs.
      The role of PPAR beta in atherosclerosis formation has not been elucidated yet
      however results of some studies indicate participation of this receptor in
      atherosclerosis. Data of studies devoted to the role of PPARs and polymorphic
      markers of these receptors in the process of atherosclerosis are reviewed.

PMID- 14671563
TI  - [Diastolic function of the heart in patients with chronic heart failure and
      methods of diagnosis of its impairment by tissue Doppler echocardiography].
AB  - Negative role of diastolic dysfunction in the heart failure formation is out of
      doubt now. But the problem of complex diagnostics of this dysfunction is still
      open. New scientific and technical developments widen our understanding of
      diastolic function of the heart and possibilities of its assessment in patients
      with chronic heart failure. One of these possibilities is the use of tissue
      doppler imaging. Modern concepts of the role of diastolic dysfunction in heart
      failure as well as detailed characteristics of the novel noninvasive method of
      its diagnosis are presented in this review.

PMID- 14671564
TI  - [Brugada syndrome].
AB  - The Brugada syndrome is a clinical-electrocardiographic diagnosis characterized
      by syncopal episodes or sudden death (caused by ventricular tachycardia and
      ventricular fibrillation) in patients with a structurally normal heart with a
      characteristic electrocardiographic pattern consisting of ST segment elevation in
      precordial leads (Vl-V3) and a morphology of the QRS complex resembling right
      bundle branch block (the latter can transiently disappear). Timely diagnosis and
      adequate treatment may essentially decrease mortality of this disease. In our
      review we have summarized results of recent studies of etiology, pathogenesis,
      clinical picture, diagnosis and treatment of the Brugada syndrome.

PMID- 14671565
TI  - [New guidelines of the Joint National Committee (USA) on Prevention, Diagnosis
      and Management of Hypertension. From JNC VI to JNC VII].
AB  - Need for update of guidelines of the Joint National Committee (USA) on
      Prevention, Diagnosis and Management of Hypertension was based on necessity to
      adopt changes based on results of recent studies as well as creation of more
      simple and convenient variant for practical physicians. Compared with JNC VI most
      important changes concerned classification of blood pressure (BP) levels and
      approaches to drug therapy. New category "prehypertension" was introduced and 2
      stages of hypertension distinguished: stage I - systolic BP 140-159 mm Hg or
      diastolic 90-99 mm Hg, stage II - systolic BP 160 mm Hg or higher, diastolic BP
      100 mm Hg or higher. Diuretics were recommended as drugs of first choice and
      wider use of drug combinations encouraged. Some statements of JNC VII report have
      been criticized by some hypertension authorities.

PMID- 14671566
TI  - [Left ventricular hypertrophy in hypertension. Part II. Prognostic value of left
      ventricular hypertrophy].
AB  - This part of review is based on results of prospective studies of prognostic
      value of left ventricular hypertrophy defined by electro- or echocardiographical
      criteria. Increased risk of cardiovascular complications has been found to be
      associated with left ventricular hypertrophy detected not only by voltage ECG
      criteria but also by ST-segment and T-wave changes in left precordial leads. Left
      ventricular myocardial mass is an independent factor of prognosis too. Prognostic
      significance of left ventricular hypertrophy depends on echocardiographical
      criteria used and on age, sex, race of patients and presence of coronary heart
      disease. Unfavorable prognostic significance of left ventricular hypertrophy
      becomes evident after several years of follow-up. Concentric left ventricular
      remodeling is also associated with increased risk of cardiovascular
      complications, however its value for prognosis is inferior to that of left
      ventricular hypertrophy.

PMID- 14671567
TI  - [Metoprolol in the treatment of essential hypertension].
AB  - In the review the basic studies devoted to researching of effectiveness of
      metoprolol in treatment of essential hypertension and also influence of this drug
      in the prognosis in this group of patients, are summarized. The specification on
      pharmacokinetic properties of the drug is shown. Outcomes of two studies (BCAPS
      and ELVA) devoted to influence of metoprolol on progression of atherosclerosis in
      patients with the risk factors are explained. The outcomes of these trials have
      confirmed, that the long-term therapy with metoprolol is one of the factors
      retentive atherosclerosis progression and allow more precisely to judge about
      mechanisms of positive influence of metoprolol therapy on the prognosis of the
      patients with cardiovascular diseases.

PMID- 14671568
TI  - [Experimental and clinical audiology: current status and trends of development].
AB  - The article presents results of experimental and clinical trials obtained in the
      National Research Center for Audiology and Hearing Rehabilitation and other
      leading research centers which studied mechanisms of primary auditory perception
      including cellular and membrane levels; nature of hair cell motor and
      electromotility, otoacoustic emission generation, effects of efferent system;
      nature and mechanisms underlying hereditary hypoacusis and deafness; regeneration
      of hair cells. Rehabilitation of deaf patients by means of cochlear implantation
      and optimization of universal audiological screening programs are described.

PMID- 14671569
TI  - [Hearing disorders in children: epidemiological evidence].
AB  - The data of surdological regional services served the basis for a comparative
      epidemiological analysis of hearing disorders in children. The analysis of the
      data showed that systemic mass check-ups of children is effective for prevention
      of hypoacusis. It is recommended to follow-up children with insignificant and
      unilateral hearing loss. There is a trend to growing occurrence of conductive and
      mixed hypoacusis in children. Its causes are analysed. Etiological factors of
      hearing problems in children were investigated. The authors believe that by the
      causes of hearing loss in children one can judge about regional health service
      quality.

PMID- 14671570
TI  - [Age-specific changes in otoacoustic emission].
AB  - The relation of age and external and middle ear parameters with otoacoustic
      emission (OAE) characteristics was studied. Ear canal equivalent volume (ECV),
      static compliance and tympanometric gradient were measured. Transient evoked OAE
      (TEOAE) and distortion product of OAE (DPOAE) were recorded. Measured parameters
      included: average TEOAE and DPOAE levels, TEOAE spectral peak level and DPOAE
      maximum level, TEOAE and DPOAE dominant frequencies as well as frequency
      corresponding to minimum DPOAE level. The analysis of variance demonstrated a
      significant interrelationship between subject's age and all TEOAE and DPOAE
      parameters. External and middle ear parameters had no significant influence on
      OAE. The only exception was ECV which had certain relation to TEOAE spectral peak
      frequency. The results obtained demonstrated that OAE age-related changes were
      predominantly determined by processes taking place within its generators system,
      i.e. at the outer hair cells level.

PMID- 14671571
TI  - [Role of electrocochleography in identification of labyrinthine hydrops].
AB  - We studied potentialities of extratympanic electrocochleography (ETECG) in
      detection of labyrinthine hydrops (LH) in 50 patients who had an audiological
      picture of unilateral neurosensory hypoacusis. The patients were divided into two
      groups: group 1 patients suffered from attacks of systemic vertigo typical for
      Meniere's disease; group 2 patients had no vestibular complaints. ETECG results
      were compared to the dynamic range, results of otoacoustic emission and brain
      stem response, vestibulometry with electronystagmography (data of bithermal
      caloric test as most informative). The comparison indicated advantages of ETECG
      used alone and in combination with other tests.

PMID- 14671572
TI  - [Characteristics of neurosensory hypoacusis and perspectives of its differential
      diagnosis basing on registration of evoked otoacoustic emission].
AB  - The examination of 135 patients with neurosensory hypoacusis and 97 otologically
      healthy persons has determined parameters of delayed otoacoustic emission and
      otoacoustic emission at the frequency of the distortion product for etiologically
      different forms of neurosensory hypoacusis. These parameters allowed selection of
      statistically significant homogeneous groups. Basing on a total of parameters of
      evoked otoacoustic emission in each homogeneous group and affiliation of an
      individual patient to one of the above groups one can identify genesis of
      neurosensory hypoacusis.

PMID- 14671573
TI  - [Registration of various classes of otoacoustic emission in definition of
      acoustic sensitivity in different forms of neurosensory hypoacusis].
AB  - To establish correlations between parameters of otoacoustic emission and
      audiometric thresholds, we have examined 30 ears (28 patients) with high
      frequency neurosensory hypoacusis. The analysis of the findings was made in
      microstructural frequency resolution. It was discovered that peaks of spontaneous
      otoacoustic emission correspond by frequency range to minimal thresholds of
      audibility in all the cases. Minimal values of audibility thresholds correlate
      also by frequency with maximal values of amplitudes of the response signal of
      delayed evoked otoacoustic emission with good sigmal/noise in all the examinees
      as well. 23 ears demonstrated 'mirrow' correlation of pure-tone audiogram with DP
      gram - a rise in behavioral thresholds corresponds to amplitude-lowering response
      signals in frequency range 3-6 kHz.

PMID- 14671574
TI  - [Cochlear function study by registration of otoacoustic emission of different
      classes in persons exposed to intensive industrial noise].
AB  - To investigate the condition of the acoustic analyzer and to identify early signs
      of affection of the internal ear receptors in persons exposed to intensive
      industrial noise, we examined engine-drivers exposed to noise for 1 to 20 and
      more years. The findings suggest that registration of otoacoustic emission of
      various classes may hold perspective for obtaining information about the
      condition of preneural micromechanical elements of the internal ear in hypoacusis
      of noise origin. This method detects the earliest cochlear involvement when tonic
      thresholds are low informative for diagnosis and prediction of hearing loss.
      Further study of the issue by regular audiological monitoring of persons exposed
      to intensive industrial noise including registration of otoacoustic emission is
      required.

PMID- 14671575
TI  - [Cochlear implantation (problems, methods, perspectives)].
AB  - We suppose that topical problems of cochlear implantation comprise preoperative
      diagnosis of the acoustic nerve condition, programmimg of the speech processor
      using objective evaluation of acoustic function, design of new strategies of
      stimulation of speech processors and criteria of choice for existing strategies.
      In solving the above problems, the following methods are of special importance:
      registration of electrically evoked potential of acoustic nerve action (EPAN),
      registration of electrically evoked acoustic potentials (EAEP), registration of
      electrically evoked reflex of the musculus stapedius (ERMS). 27 patients with
      cochlear implants were examined to evaluate the above methods in terms of speech
      prosesses programming. The findings enable the conclusion that all three methods
      can be successively used in programming of the speech processor. While EPAN and
      EAEP can be used for approximate estimation of sensation threshold, ERMS
      registration is highly effective for determinaion of maximal comfortable level of
      stimulation.

PMID- 14671576
TI  - [Current approaches to choice of patients for cochlear implantation and prognosis
      of surgical results].
AB  - The authors analyse the results of examination of 225 patients for defining
      indications to cochlear implantation, give grounds for a thorough examination
      with allied specialists, outline the indications in 93 patients and predict
      rehabilitation efficacy after cochlear implantation in different groups of
      patients.

PMID- 14671577
TI  - [Comparative analysis of approaches to surgical cochlear implantation in adults
      and children].
AB  - The aim of a surgical stage of cochlear implantation (CI) is to place the
      implanted part of the device in the temporal space. Criteria of the decision on
      the side of the intervention and components of it in CI are outlined. To help
      selection of an optimal variant of surgical intervention in CI at the initial
      stage, the techniques of the implanted parts insertion are reviewed. Types of
      skin cuts, approaches to the cochlea, location of cochleostoma, methods of fixing
      the stimulator are described. The importance of intraoperative registration of
      the musculus stapedius reflex and action potential of the acoustic nerve in
      response to cochlear electrostimulation is emphasized. Basing on the experience
      of treating 38 deaf patients, the author states that for effective performance of
      the operation it is desirable to conduct reverse U-cut of the skin, make
      posterior tympanostoma, cochleostoma in the basic cochlear margin, suturing of
      the cut with intracutaneous suture.

PMID- 14671578
TI  - [Contralateral electrically evoked reflex of the musculus stapedius in patients
      with cochlear implant].
AB  - Registration of electrically evoked reflex is widely applied in rehabilitation of
      patients by cochlear implantation. As a rule, visual assessment of the
      ipsilateral reflex is made intraoperatively for functional evaluation of surgical
      results. Of interest is use of contralateral electrically evoked reflex of the
      musculus stapedius in the course of adjustment of the speech processor. We
      studied the latter reflex in 20 patients with cochlear implants Cl24M and Cl22
      made by 'Cochlear'. 13 patients used Sprint processors, 7 patients - Spectra
      ones. Zodiak impedansometer registered the reflex which was recorded in 12
      patients. The threshold of the reflex registration correlated well with
      comfortable perception of loudness. Most of the patients evaluated threshold (for
      the reflex) sound perception as the sound of moderate loudness. The conclusion is
      made that registration and analysis of the contralateral electrically evoked
      reflex can assess a comfortable stimulation level in adjustment of speech
      processors in patients with cochlear implants.

PMID- 14671579
TI  - [Cochlear implantation and vestibular function].
AB  - To determine the risk of injuring a peripheral part of the vestibular analyzer in
      usage of an intracochlear implant in patients with varying deafness, the author
      compared her data and data from other clinics making examinations according to
      similar methods: implantation was conducted using multichannel intracochlear
      electrode, the program of otoneurological examination employed the caloric test,
      the patients were examined before and after the operation.

PMID- 14671580
TI  - [Acoustic perception in patients using a cochlear implant before and after
      adjustment sessions].
AB  - The aim of the study was comparison of perception of pure tones and speech
      intelligibility in postlingually deaf patients using a cochlear implant before
      and after elective adjustment sessions. 10 patients were examined: 5 children
      (age 8-15.5 years) and 5 adults with cochlear implants NUCLEUS CI22 (6 patients)
      and NUCLEUS CI24 (4 patients) produced by COCHLEAR (Australia). It was found that
      between the adjustment sessions all the implanted patients showed deteriorated
      perception of pure tones throughout all the frequencies and therefore their
      speech intelligibility worsened. The recommended period between the adjustments
      is 6 months as acoustic perception degraded with time. However, such observations
      are not significant in view of insufficient material. Objective assessment of
      acoustic perception is necessary because subjective sensations are not always
      true.

PMID- 14671581
TI  - [A technique of esthetic rehabilitation of patients with microtia after
      meatotympanoplasty].
AB  - The paper presents peculiarities of surgical rehabilitation of patients with
      congenital malformation of the external and middle ear after meatotympanoplasty;
      demonstrates feasibility of using bioinert synthetic material, silicon, as
      implant in creating the frame of the floor of the auricle and cosmetic results
      with criteria of their assessment; characterizes auriculoplasty in lack of
      hairless skin above the acoustic meatus; outlines complications and their causes;
      reports a case of a male patient who has undergone a complete rehabilitation of
      microtia.

PMID- 14671582
TI  - [Surgical treatment of patients with exudative otitis media].
AB  - The article concerns peculiarities of surgery for chronic exudative otitis media
      (CEOM). The significance of miringotomy, tympanostomy, tympanotomy and
      tympanoantrotomy is demonstrated. The experience of the authors in surgical
      treatment and postoperative management of CEOM is reviewed. Of primary importance
      is valid selection of patients for each operation and choice of ventilatory tubes
      depending on the disease stage. Incidence rate and causes of recurrences in
      respect to the patients' age are presented and the role of follow-up in
      prevention of CEOM recurrences is shown. Use of temporal bone computed tomography
      in CEOM is specified. Key words: exudative otitis media, tympanostomy,
      ventilation tubes, CT of the temporal bone.

PMID- 14671583
TI  - [Soft palate muscles electrostimulation in treatment of children at different
      stages of exudative otitis media].
AB  - We studied efficacy of electrical stimulation of soft palate muscles in 180
      patients (292 ears) with various stages of exudative otitis media (EOM). The
      analysis of the results covered 172 patients. 8 patients withdraw because of the
      4th (fibrous) stage of the process (n=4) and incomplete treatment course (n=4).
      Normalization of audibility thresholds and tympanometric parameters was observed
      after 10 sessions of electrostimulation in 129 (75.0%) patients with early EOM
      stages. The effect persisted for 1 year. 3 (1.7%) patients with EOM stage II and
      40 (23.3%) patients with stage III failed the treatment. For them bypass
      operation was recommended. Postoperative electrostimulation of the acoustic tube
      muscles and standard manipulations were made. Faster recovery of audiometric and
      tympanometric parameters were recorded in all the patients. Thus, electric
      stimulation of acoustic tube muscles can be recommended for children with EOM
      stage I, for most of the children with stage II and for children at stage III in
      postoperative period after tympanostomy with insertion of the bypass.

PMID- 14671584
TI  - [Treatment strategies in exudative otitis media in children with aquired cleft
      lip and palate].
AB  - The paper presents incidence of hearing problems in 100 children with aquired
      cleft lip and palate (ACLP) aged 1 to 16 years. An age aspect of the problem is
      analysed. The patients were at different stages of rehabilitation for ACLP.
      Conservative and surgical policies in management of children with exudative
      otitis media and ACLP are analysed. Surgical results depending on the disease
      stage are provided.

PMID- 14671585
TI  - [Measurement of output sound pressure in a real ear to raise efficacy of
      electroacoustic hearing correction].
AB  - Fifty adult patients with neurosensory hypoacusis of different severity
      participated in the study of feasibility of using analytic computer systems in
      selection of optimal regimes of acoustic aid function with use of pressure
      measurement in the real ear. The results have shown that measurement of the
      frequency response in the camera of 2 sm(3) in volume is unable to predict the
      function of the acoustic aid in each individual case. Most of the acoustic aid
      users need correction of the program adjustment. The efficacy of electroacoustic
      correction should be evaluated on the basis of measurements of output sound
      pressure in a real ear as most reliable and significant. The results of the study
      are useful in conduction of hearing prosthetic correction.

PMID- 14671586
TI  - [Electrokinetic activity of the buccal mucosa epitheliocytes in patients with
      lichen planus].
AB  - The electrokinetic activity of buccal epithelial cells drops in patients with
      lichen planus. The most pronounced changes develop in patients with severe forms
      of the disease (exudative hyperemic and erosive ulcerative). The functional
      activity of the epithelium does not depend on sex or presence of metal dentures;
      the effect of the disease duration is negligible, while the underlying somatic
      disease is significant. The electrokinetic activity of epithelial cells is
      sharply reduced in cardiovascular patients with lichen planus of the buccal
      mucosa. Increase of electrokinetic activity of epitheliocytes after local drug
      therapy for lichen planus clinically manifests by epithelialization of erosions,
      which recommends this test for predicting the course and outcome of lichen
      planus.

PMID- 14671587
TI  - [Histamine-releasing activity of acrylic plastic materials].
AB  - The histamine-releasing activity of acrylic plastics (ftorax, stomacryl,
      ethacryl) used for denture making and maxillofacial prostheses was studied by
      automated and computer-aided fiber glass method for evaluating histamine release
      from whole blood basophils. The results indicate that some plastics made by the
      thermo-polymerization method (for example, ethacryl) are characterized by higher
      histamine-releasing activity than the plastics made by polymerization using
      superhigh frequency electromagnetic energy. The method is recommended for
      preliminary screening of new polymers intended for dentistry and for individual
      selection of materials with consideration for their safety and strength
      characteristics.

PMID- 14671588
TI  - [Characteristics of leukocytic markers in patients with chronic generalized
      periodontitis during exacerbation].
AB  - The immune status of patients with periodontitis was studied using monoclonal
      antibodies. Two variants of the immune status were distinguished: with high and
      low reactivity of T cellular system. The data on the presence of receptors and
      apoptosis markers on lymphocytes, neutrophils, and monocytes of patients with
      periodontitis are presented for the first time. The authors recommend to take the
      results of this study into consideration when treating patients with chronic
      periodontitis.

PMID- 14671589
TI  - [Efficacy of leukinferon immunocorrection in patients with maxillofacial
      phlegmons].
AB  - Clinical and immunological studies were carried out in patients with
      maxillofacial phlegmons treated by traditional methods and by traditional therapy
      supplemented by immunocorrection (leukinferon). Addition of leukinferon to basic
      therapy had a pronounced clinical and immunomodulating effect, which resulted in
      shorter hospitalization period and virtually complete recovery of the main
      immunological parameters, in contrast to traditional therapy alone. The most
      demonstrative parameters were the expression of the neutrophil granulocyte
      membrane receptors and the relationships between T-lymphocyte subpopulations,
      which prompted using them as the most significant diagnostic markers indicating
      the disease severity and treatment efficiency.

PMID- 14671590
TI  - [Lymphotropic therapy for acute purulent odontogenic jaw periostitis].
AB  - The structure of the gingival mucosa was studied by optic microscopy in patients
      with acute purulent odontogenic maxillary periostitis treated traditionally and
      receiving lymphotropic therapy. Lymphotropic administration of the antibiotic
      during 2 days resulted in less pronounced dilatation of the interstitial spaces
      and lymph vessels adjacent to the molars and higher counts of lymphocytes,
      monocytes, and macrophages. This indicated high efficiency of lymphotropic
      therapy of acute purulent maxillary periostitis for molars. Microcirculation
      parameters and tissue leukocyte cytogram in gingival mucosal tissue adjacent to
      the canines and premolars differed negligibly in patients treated by different
      methods.

PMID- 14671591
TI  - [Endo-prosthetics of the temporomandibular joint: results of using different
      methods based on data of Central Institute of Dentistry clinic].
AB  - Results of using different types of endoprostheses for repair of the
      temporomandibular joint (TMJ) are discussed. The main advantages and drawbacks of
      the method of endoprosthetic treatment of the mandibular condylar process,
      detected during the immediate and remote postoperative periods, are described.
      The biomechanics of mandibular movements in prostheses of the joint is presented.
      Results of using complete endoprosthesis of the TMJ, designed with consideration
      for mandibular movements biomechanics and experience gained in the use of various
      types of the joint endoprostheses are presented.

PMID- 14671592
TI  - [Radiotherapy of lymphosarcoma of the major salivary glands].
AB  - Twenty patients with cytologically verified diagnosis of lymphosarcoma of the
      major salivary glands (15 with lymphosarcoma of the parotid gland and 5 with
      lymphosarcoma of the submandibular gland) were treated by radiotherapy. Twelve
      patients presented with stage I E, 7 with stage II E, and 1 with stage IV EO.
      Metastases in the cervical lymph nodes were diagnosed in 7 patients. Total focal
      doses for the primary tumor and metastases were 30-40 Gy during 3-4 weeks. The
      observation of 2-4 years showed that radiotherapy led to cure of 12 (60+/-15.4%)
      patients. No trends to relapses and generalization of the process were observed.
      No preventive exposure of the lymph discharge zones was carried out.

PMID- 14671593
TI  - [Theoretical and clinical prerequisites for the use of fragments of molar roots
      as abutment for dentures].
AB  - Experimental and clinical studies confirmed the possibility of using fragments of
      a multi-root tooth as abutment tooth for a bridge denture. When planning
      orthodontic treatment, choosing the abutment teeth, designing the denture, and
      treating the patient the orthodontist should be able to use the information on
      the maximum allowable loading of the fragments of resected teeth. A positive
      factor in utilization of the remaining tooth fragment is the ratio of clinical
      crown and root length, which should be inversely proportional. The study showed
      that retention of the morphofunctional integrity of dentition is possible when
      using dentures ensuring the optimum regulation stress (no higher than
      physiologically tolerable) in abutment tissues. Analysis of remote clinical and X
      ray data showed normalization of the periodontal function of tooth fragments
      after tooth-sparing operations in cases when the patients were fitted with
      prostheses with consideration for theoretically valid methods for estimation of
      reserve force.

PMID- 14671594
TI  - [The significance of the size and type of surface of prepared teeth for retention
      of permanent dentures fixed with zinc-phosphate cement].
AB  - The purpose of this paper was to establish, in vitro, the impact of different
      sizes and prepared teeth roughness on the adhesion strength with cast crowns.
      Twenty human intact premolars were used in the experiment. They were prepared and
      divided into two groups depending on the fineness of diamond prepared
      instrumentation. Sizes of prepared teeth were calculated mathematically, while
      the dentine roughness was measured by a profile meter. The cast crowns were made
      by a standard method for each group. The crowns were then cemented with a zinc
      phosphate cement. After seven days, testing of prepared teeth and cast crowns
      bonding strength was carried out mechanically in an electronic dynamometer. On
      the basis of the obtained results the relationship between the size and the
      accomplished roughness with the obtained values of the retention forces is
      observed. At the constant convergence angle of the stamp the retention is
      proportional to the stamp size and the roughness profile.

PMID- 14671595
TI  - [Heart rhythm variability as a criterion for selecting anesthesia for
      maxillofacial surgical procedures in children].
AB  - The aim of this study was to improve the quality of anesthesia for maxillofacial
      operations in children. The authors suggest the criteria of its adequacy, based
      on analysis of heart rhythm variability. The most informative characteristics of
      heart rhythm structure were detected on the basis of the results of examinations
      of 100 children aged 5 months to 16 years. The data indicate that in children
      subjected to maxillofacial surgery the most hazardous (as regards the risk of
      arrhythmia) anesthesia is mask narcosis with fluothane; the optimal narcosis is
      endotracheal and intravenous.

PMID- 14671596
TI  - [Treatment of torsion abnormalities of central upper incisors caused by super
      compact teeth].
AB  - A super-compact retained tooth is often responsible for rotation of a tooth round
      its axis; the retained tooth should be removed after preliminary x-ray
      examination of the site of abnormality. A great variety of etiopathological
      factors are responsible for the abnormality, and hence, the approaches to the
      choice of treatment are numerous. Rotation of teeth during orthodontic treatment
      involved stretching and strain of connective tissue fibers, which are not
      intended for rearrangement, and therefore the results are not stable. A long
      period of retention is needed for adaptation of tissues to a new position of the
      tooth.

PMID- 14671597
TI  - [General issues of medical care in multiple trauma].
AB  - Experience in diagnosis and treatment of patients with combined trauma is
      presented. The clinicoanatomic classification of combined traumas with their
      division into 7 groups is proposed. The process of medical care is subdivided in
      4 stages - prehospital, critical care, specialized clinical and rehabilitation.
      The number of patients and their qualitative characteristics at each stage are
      different. The majority of the lethal outcomes occur at prehospital and critical
      care stages. Improvement of medical care at the prehospital stage may be realized
      trough creation of diagnostic and treatment algorithms, at critical care stage -
      by adequate infusion-transfusion therapy and determination of surgical care
      priority. Prophylaxis and treatment of complications are very important at the
      second and third stages. At the rehabilitation stage 84,6% patients need
      treatment of locomotor lesions, 14.5% - damages of the brain, 0.5% - damages of
      the spinal cord. Traumas of the thorax and the abdomen don't require long
      rehabilitation.

PMID- 14671598
TI  - [Comparative assessment of the results of open carotid endarterectomy and carotid
      aftery stenting].
AB  - A comparative study of 48 carotid stent grafting and 23 open carotid
      endarterectomies was carried out. Patients of both groups were comparable by
      cerebrovascular insufficiency degree and concomitant diseases. General rate of
      complications after carotid stent grafting (CSG) was 5.1%. There was a small
      ischemic stroke with right-sided hemiparesis and aphasia in one patient during
      CSG. Complete regress of the neurological symptoms was seen on the 5th day. In
      the nearest postoperative period after CSG there was a big ischemic stroke in the
      territory of MCA in one patient. Rate of complications after open carotid
      endarterectomy (OCEAE) was 8.7% Transient ischemic attacks were seen in 2
      patients in early postoperative period. Paresis of the IX cranial nerves was in
      one patient. In long-term postoperative period after CSG 2 patients died due to
      cardiac causes. One patient died 18 months after OCEAE due to ischemic stroke. In
      long-term period after OCEAE restenosis of the internal carotid artery was seen
      in 4.5% cases, while there were no restenosis after CSG. It is concluded that CSG
      is an effective method of treatment of carotid stenosis with lower lethality and
      postoperative complications rate compared with OCEAE. Indications for CSG are
      symptomatic stenosis of ICA (>60%), asymptomatic stenosis of ICA(>70%), two-sided
      lesions of the carotid arteries, carotid stenosis with lesions of other
      brachiocephalic arteries, insufficiency of Willis circle.

PMID- 14671599
TI  - [Thoracoscopy in surgery of thoracic wounds].
AB  - One hundred and sixty-eight thoracoscopic operations were performed in patients
      with closed (47.5%) and open (52.5%) trauma of the chest. Thoracoabdominal
      injuries were diagnosed in 23.9% patients. Thoracoscopic surgeries were performed
      in 79.8% patients, surgeries from the mini-approach - in 17.3%. Injuries
      uncorrectable by endosurgically were diagnosed during thoracoscopy in 2.9%
      patients. Indications for urgent thoracoscopy in thoracic injuries are the
      following: 1) middle and small hemothorax or hemopneumothorax; 2) suspicion for
      heart wound; 3) suspicion for diaphragm injury; 4) tense pneumothorax. Surgical
      policy and technique of endosurgeries in open thoracic trauma are optimized. Up
      to-date surgical policy based on thoracoscopy permitted us to improve results of
      surgical treatment: to reduce lethality by 4.7%, number of complications - 2.9
      times and completely avoid unjustified 'diagnostic' thoracotomies. Mini-invasive
      surgical methods promoted early rehabilitation of patients with trauma of the
      chest.

PMID- 14671600
TI  - [Changes in blood linear velocity in the inferior cava vein after combined trauma
      in early posttraumatic period].
AB  - Blood linear velocity in inferior cava vein was measured in 74 persons (men and
      women) aged from 18 to 55 years including 29 healthy volunteers and 45 patients
      with various severity of trauma and different assessment of its severity by
      APACHE-2 scale. Correlation between APACHE-2 index and changes of ratio of blood
      linear velocities in inferior cava vein was demonstrated. It is concluded that
      ratio of blood linear velocities in inferior cava vein can be used as a criterion
      of treatment efficacy in patients with combined trauma in early postoperative
      period.

PMID- 14671601
TI  - [Bypass surgeries from remote vascular beds in the treatment of critical limb
      ischemia in elderly and old patients].
AB  - The problem of surgical treatment of elderly and old patients with critical limb
      ischemia and severe concomitant diseases is discussed. Surgical bypass from
      remote vascular beds is the only real possibility of effective care for such
      patients with the lowest risk. The results of treatment of 90 patients with
      critical limb ischemia were analyzed. The surgical technique is described in
      details. Modified methods of proximal anastomosis creation and technology of safe
      installation of graft into subcutaneous canal in subclavial-femoral bypass,
      surgical technique in femoral-femoral and ileo-femoral cross-over bypass are also
      described. Results demonstrate high efficacy of these surgeries and their lower
      risk. It is concluded that improved surgical technique permits to expand
      indications for surgery in elderly and old patients and to improve immediate and
      long-term results.

PMID- 14671602
TI  - [Reflexotherapy in patients with ischemic angiopathies of the lower extremities].
AB  - Comparative assessment of different methods of reflexotherapy - RT (acupuncture,
      electroacupuncture, pharmacopuncture and the termopuncture) in treatment of
      ischemic angiopathies of the lower extremities is presented. One hundred and
      twenty-four patients with ischemic angiopathies were treated, 86 of them had I -
      II stage of the disease, 38 - III stage. Diagnosis of the disease and assessment
      of treatment efficacy were based on clinical, laboratory and special instrumental
      examinations. Functional examinations revealed equal reaction of peripheral blood
      flow to different RT methods. Moderate hypocoagulation compared with the baseline
      was demonstrated. Clinical symptoms (improvement of the general condition,
      decrease of pain syndrome) and improvement of biochemical and physiological
      parameters were criteria of successful treatment. The results of the study helped
      to develop methods of treatment with different variants of RT and to recommend
      them in clinical practice for combined treatment of this disease.

PMID- 14671603
TI  - [Injuries of pancreatoduodenal organs].
AB  - Ten-year experience of treatment of 213 patients with trauma of the pancreas and
      56 patients with trauma of the duodenum is analyzed. Combined injury of other
      organs was seen in 80% patients. Diagnostic policy included intraoperative
      revision in open abdominal trauma and dynamic observation with US,
      roentgenography, CT and laboratory tests in closed trauma wich doesn't require
      urgent surgery. The diagnosis was verified during laparoscopy and contrast
      duodenography. Surgical treatment results in patients with trauma of the pancreas
      depending on the variant of surgery are analyzed. The role of drug treatment of
      traumatic pancreatitis with 5-ftoruracil and octreotid is stressed. It is
      demonstrated that these principles allowed us to reduce complications rate to
      11.7% and lethality to 6.7% from 71.7% and 37.0% respectively. It is established
      that suturing of duodenal wall on the decompressive nasoduodenal tube is
      effective within 6 hours after trauma. Later, for prophylaxis of suture
      insufficiency the duodenum must be switched off. Adequate drainage and depression
      of secretion with octreotid are very important for success of surgery. In this
      approach there were no cases of sutures insufficiency among 16 patients in the
      last 3 years.

PMID- 14671604
TI  - [Treatment of gastroduodenal ulcer bleedings in a general hospital of emergency
      care].
AB  - Treatment of patients with gastroduodenal ulcer bleedings in a general hospital
      of emergency care is a complex of measures including of endoscopic diagnosis and
      stopping of bleeding, use of effective antisecretory drugs with obligatory
      laboratory control of acid-producing function of the stomach, surgical treatment
      and eradication of H. pylori. Up-to-date methods of endoscopic hemostasis -
      spirituous infiltration, argon-plasma coagulation, clipping of vessels in ulcer
      and also their combination in difficult cases - provide reliable hemostasis and
      allow to avoid urgent surgery. Recently we succeeded in reducing the rate of
      urgent surgeries performed at the height of bleedings from 70 to 40%. These
      methods can be recommended for clinical practice because they reduce
      significantly lethality rates in patients with severe conditions.

PMID- 14671605
TI  - [Treatment of patients with perforated pyloroduodenal ulcers].
AB  - Results of treatment of 206 patients with perforated gastroduodenal ulcers were
      analyzed. Atypical clinical picture of perforated ulcer in some patients led to
      diagnostic mistakes. Diagnostic algorithm including videolaparoscopy in difficult
      cases is proposed. The study group included 183 patients who have undergone open
      suturing of perforated ulcer, in 17 patients videolaparoscopic suturing was
      performed. Combination of perforation with other complications of ulcer disease
      required extended surgery in 6 patients. Diagnostic algorithm after surgery for
      correct antiulcer therapy is developed.

PMID- 14671606
TI  - [Influence of gastroesophageal reflux on the reparative process in burn of the
      esophagus].
AB  - Experience in endoscopic examination and treatment of 282 patients with isolated
      and combined chemical burn of the esophagus (CBE) of different severity is
      presented. Endoscopic treatment, performed in combination with chemotherapy,
      consisted in irradiation of burn surface with low-energy laser 'Mustang' through
      the canal of the endoscope. The procedure was performed 3 times a week up to
      complete epithelization of burn ulcers. Both in primary
      esophagogastroduodenoscopy and in repeated examinations sphincter function of the
      cardia, presence and sizes of axial hiatal hernia, changes of esophageal mucosa
      and presence of gastroesophageal reflux were analyzed. It is demonstrated that
      CBE was associated with dysfunction of the cardia in more than 90% cases. Rate of
      erosive and ulcerous reflux-esophagitis was 24.6-34%; cicatrix stricture of the
      esophagus - 6.3-12.2% in isolated and combined CBE, respectively. Severity of
      reflux-esophagitis and its complications was determined by severity of chemical
      burn.

PMID- 14671607
TI  - [Up-to-date methods of cell therapy in treatment of burns].
AB  - Complex of methods for repair of wounded and burned skin with transplantation of
      keratinocytes and fibroblasts grown in vitro is proposed. Five different tissue
      constructions may be used. Original method of skin recovery based on use of alive
      equivalent of skin is developed. Results of its clinical application are
      presented. It is concluded that cell constructions may be used in combined
      treatment of wounds and burns.

PMID- 14671608
TI  - [Subtotal colectomy: 20 years' experience].
AB  - Results of surgical treatment of 338 patients (1984-2002) with complicated cancer
      of the left half of the colon were analyzed retrospectively. Patients who had
      undergone Hartman's surgery and subtotal colonectomy were comparable by age, time
      of hospitalization, stage of cancer and concomitant diseases. Immediate results
      of treatment (postoperative complications, postoperative stay, postoperative
      lethality) don't differ significantly. Long-term results demonstrate important
      difference in survival. Mean survival of patients after Hartman's surgery was 3
      years 6 months, after subtotal colonectomy - 9 years 6 months. It is concluded
      that subtotal colonectomy is the surgery of choice in the treatment of patients
      with complicated cancer of colon's left half.

PMID- 14671609
TI  - Role of coagulation testing in predicting bleeding risk.
AB  - Coagulation testing is employed widely prior to open surgery and invasive
      procedures. This is based on the assumption that such testing is of clinical
      value in the prediction of bleeding. In order to improve the clinical
      understanding of the potential limitations of first-line coagulation tests used
      in this way, we have systematically reviewed the literature that addresses the
      value of routine coagulation testing in helping to predict bleeding risk. We
      conclude unreservedly that indiscriminate coagulation testing is not useful in a
      surgical or a medical setting. This is due to the limited sensitivity and
      specificity of the tests, coupled with the low prevalence of bleeding disorders
      resulting in a high number of false positives, poor positive predictive value for
      bleeding and numerous false negatives resulting in false reassurance. Since most
      abnormal results can be predicted and most cases of significant bleeding disorder
      identified from a complete clinical assessment, the employment of selective
      laboratory testing is more cost-effective and represents evidence-based clinical
      practice.

PMID- 14671610
TI  - Myeloma management guidelines: a consensus report from the Scientific Advisors of
      the International Myeloma Foundation.
AB  - These consensus guidelines have been compiled with input from the Scientific
      Advisors of the International Myeloma Foundation. Their production involved
      several steps including: A 3-day Scientific Advisors meeting, during which each
      specific area was presented and discussed (May 2002). Review of key literature,
      especially randomized study results, but also Medline, Internet, Cochrane
      database searches, and prior guidelines (Br J Haematol 115: 522-540, 2001).
      Feedback from patients participating in the International Myeloma Foundation,
      patient programs. These guidelines encompass both the published literature and
      expert opinions. Recommendations based upon expert opinions are identified as
      such. The intent is for the guidelines to be international in scope, plus provide
      recommendations for both clinical practice and research approaches. 'Consensus'
      reflects general, although not necessarily unanimous, agreement. Details are
      discussed as appropriate. For convenience, the recommendations are divided into:
      1. Diagnostic criteria. 2. Staging and prognostic factors. 3. Frontline therapy.
      4. High-dose therapy and transplant. 5. Maintenance therapy. 6. Supportive care
      and management of specific complications. 7. Novel therapies and new
      technologies.

PMID- 14671611
TI  - A review of recruitment criteria, patient characteristics and results of CHOP
      chemotherapy in prospective randomized phase III clinical trials for aggressive
      non-Hodgkin's lymphoma.
AB  - It has frequently been questioned whether results of trials can be generalized to
      routine clinical practice. Results obtained with standard cyclophosphamide,
      doxorubicin, vincristine, prednisone (CHOP) chemotherapy for aggressive non
      Hodgkin's lymphoma in the control arm of prospective randomized phase III
      clinical trials during the past 25 years appear to be comparable. As the
      possibility to generalize trial results is favored by such consistency, we tested
      this hypothesis and tried to indicate explanatory 'moderator variables'
      (inclusion and exclusion criteria, therapy characteristics, sample sizes,
      inequalities in the distribution of patients over prognostic categories across
      different trials) in the case of divergent trial results. Trial results on
      conventional CHOP chemotherapy were obtained from literature research. Overall
      response (OR), complete response (CR) and two-year overall survival (2YS) were
      considered as outcome measures. Although OR rates and 2YS rates were within
      acceptable limits of comparability, the absolute differences within the results
      were remarkably wide, particularly with regard to CR and 2YS. Divergent rates
      could not be properly explained by differences in the moderator variables. We
      conclude that absolute results obtained with CHOP in the control arm of trials
      appeared to be poorly generalizable to routine clinical practice, particularly in
      the case of elderly patients. This analysis underlines the need for the strict
      application of internationally agreed response criteria and the WHO
      classification system, large sample sizes and stratifying patients on the basis
      of prognostic factors, preferably in intergroup clinical trials. We expect those
      factors to lead to a better consistency of results in future trials and improved
      possibilities to generalize the results.

PMID- 14671612
TI  - Effective treatment of hypereosinophilic syndrome with imatinib mesylate.
AB  - Imatinib mesylate treatment is highly effective in chronic myeloid leukaemia and
      recent data have suggested that imatinib mesylate is also effective in the
      treatment of idiopathic hypereosinophilic syndrome (HES). Six patients with HES
      were treated daily with 100 mg imatinib mesylate. Five patients had normal
      karyotype and one showed trisomy 8. RT-PCR was negative for ETV6-PDGFRB and BCR
      ABL fusion mRNAs. All patients rapidly achieved complete haematological
      remission. One patient remained in remission for more than 6 weeks after
      discontinuing treatment. No significant side effect was noted. Imatinib mesylate
      should be considered in the first-line therapy of idiopathic HES.

PMID- 14671613
TI  - No correlation between the proliferative status of Bcr-Abl positive cell lines
      and the proapoptotic activity of imatinib mesylate (Gleevec/Glivec).
AB  - Imatinib mesylate (Gleevec, formerly STI571) has been shown to be a safe and
      effective treatment for chronic myelogenous leukemia (CML). However, despite high
      rates of hematologic and cytogenetic remissions, molecular remissions are rare.
      Recent work has revealed the existence of a population of Bcr-Abl-positive,
      quiescent hematopoietic CML stem cells that are insensitive to induction of
      apoptosis by imatinib ex vivo. Thus, quiescence is postulated as a mechanism of
      molecular resistance to imatinib. To model a cell population with reduced cell
      cycle activity in vitro, we applied three different established approaches to
      block the cell cycle at the G1/S boundary using Bcr-Abl-positive cell lines.
      Subsequently, the cells were exposed to imatinib and apoptosis after 48 h of
      treatment was determined by analysis of activated caspase-3 and apoptotic DNA
      strand breaks. In these models, reduced cell cycle activity did not have a
      significant impact on the ability of imatinib to induce apoptosis. These data
      suggest that the proapoptotic activity of imatinib in vitro is not dependent on
      cell cycle transit. We conclude that resistance of primary CML cells that are
      insensitive to imatinib may be the result of molecular properties causing drug
      resistance rather than a consequence of quiescence itself.

PMID- 14671614
TI  - Bacteraemia in hospitalised patients with malignant blood disorders: a
      retrospective study of causative agents and their resistance profiles during a 14
      year period without antibacterial prophylaxis.
AB  - Bacteraemia is a major cause of morbidity and mortality in patients with
      haematological disorders during chemotherapy-induced neutropenia. The generally
      reported trend during the last two decades has been a gradual replacement of Gram
      negative bacilli by Gram-positive cocci as the major causes of bacteraemia in
      neutropenic hosts. However, data that are unaffected by the use of antibacterial
      prophylaxis are scarce. Our objective therefore was to study the incidence of
      bacteraemia with different microorganisms in a haematology centre where
      antibacterial prophylaxis has not been used during the years 1988-2001. A total
      of 1402 episodes of clinically significant bacteraemia in 927 patients were
      identified. All patients were treated in the haematology wards and had an
      underlying haematological disorder, with lymphoma, leukaemia, and myeloma
      dominating. There were 536 (58%) male, and 391 (42%) female patients, with a
      median age of 58 years. The dominating pathogens were coagulase-negative
      staphylococci (CNS) 17%, Escherichia coli 16%, alpha-haemolytic streptococci 12%,
      Staphylococcus aureus 9%, Klebsiella spp 9%, Enterococcus spp 7%, and Pseudomonas
      spp 5%. The only significant incidence change was an increase of E. faecium
      bacteraemia. The balance between Gram-negative and Gram-positive microorganisms
      was essentially stable over the 14-year period. The rates of antibiotic
      resistance were generally low and stable. Gram-negative bacteria exhibited
      resistance to fluoroquinolones after 1998. The 7- and 30-day mortality rates were
      6.3 and 15.6%, respectively, being significantly higher in patients with
      bacteraemia caused by Pseudomonas aeruginosa, Stenotrophomonas maltophilia, or E.
      faecium.

PMID- 14671615
TI  - An investigation of the effects of the MEK inhibitor U0126 on apoptosis in acute
      leukemia.
AB  - Blockade of mitogen-activated protein kinase kinase (MEK1/2), part of the
      extracellular signal-regulated kinase (ERK) or p44/42 mitogen-activated protein
      kinase (MAPK) pathway has been shown, in some instances, to cause apoptosis in
      leukemic blast cells. However, studies are contradictory and have often been
      based mainly on inhibition of cell growth in a limited number of cell lines. This
      investigation examined the effect of the potent MEK inhibitor U0126 alone and in
      combination with Ara-C on apoptosis in acute myeloblastic leukemia (AML) cell
      lines, patient acute leukemic and nonleukemic samples. Apoptosis was assessed
      flow cytometrically using Apo2.7 and AnnexinV antibodies which detect apoptosis
      at the mitochondrial and cell membrane levels, respectively. The proapoptotic
      effect of the inhibitor varied across the five cell lines tested, from highly
      significant induction of apoptosis to no apparent response. A possible
      synergistic effect with the combined use of U0126 and Ara-C was observed in one
      cell line only. The proapoptotic effect of U0126 in the most sensitive cell line
      appeared to be related to CD34 positivity. Cells from leukemic patients showed
      considerable sensitivity in two of four cases with a similar association with
      CD34 expression being evident. Interestingly, control cells did not show a
      significant effect when exposed to the inhibitor. These results suggest that
      U0126 may offer a potential alternative to standard chemotherapy with a
      particular role in the most primitive types of leukemia, these being often the
      most resistant to standard chemotherapy.

PMID- 14671616
TI  - Frequency and spectrum of hemochromatosis mutations in Tunisia.
AB  - The occurrence of the C282Y and H63D mutations of the HFE gene, responsible for
      toxic iron overload in the liver (hereditary hemochromatosis), was still unknown
      in Tunisia. We report the screening of 194 chromosomes from 97 randomly collected
      cord blood samples. The mutations were analyzed by PCR followed by DNA
      sequencing. The mild H63D and the severe C282Y mutations were found in 17.5+/
      5.34% and 0.5+/-0.97% of the alleles, respectively. The allele frequency of the
      IVS 2+4 T --> C polymorphism is high (46.4+/-7.01%) in this population. Risk for
      homozygosity for the severe C282Y mutation is present in the Tunisian population
      at a low theoretical incidence. However, due to the relatively high rate of
      consanguinity in the country, liver pathology due to HH is not to be disregarded.

PMID- 14671618
TI  - HPA-genotyping and antiplatelet antibodies in female blood donors.
AB  - Cases of passive alloimmune thrombocytopenia have been reported due to
      transfusions of blood products with antiplatelet antibodies. The aim of our study
      was to search for antiplatelet antibodies in HPA-homozygous blood donor women
      once pregnant and also to perform, in case of positivity, a retrospective
      analysis of platelet counts of the recipients of their blood products. HPA-1, -2,
      -3 and -5 genotyping were performed on 500 platelet donors (42% women).
      Circulating antiplatelet antibodies were screened for by MAIPA assay in 122 women
      who experienced at least one pregnancy and who were homozygous for either HPA-1a,
      -1b, -3a, -3b, -5a or -5b. None of the women homozygous for HPA-1 or -3 had
      circulating antiplatelet antibodies. In contrast, two of the 98 women homozygous
      for HPA-5a and one of the two women homozygous for HPA-5b had circulating
      antibodies. A retrospective analysis of the medical charts of the 37 recipients
      of 55 blood components from these three women showed no case of passive
      alloimmune thrombocytopenia. Our study indicates the presence of platelet
      specific antibodies in 2.5% of HPA-homozygous female platelet donors who were
      previously pregnant. Although none of the recipients developed passive alloimmune
      thrombocytopenia, this aspect of blood transfusion safety should be addressed by
      a large prospective trial.

PMID- 14671617
TI  - Mutations of the hemochromatosis gene in Italian candidate blood donors with
      increased transferrin saturation.
AB  - The aim of this study was to analyze the role of HFE mutations in blood donors
      with iron parameters suggesting iron overload, taking into account the regional
      distribution of HFE mutations in Italy. We studied 5880 subjects undergoing
      evaluation for blood donation eligibility, from different areas of Italy.
      Abnormal iron parameters were defined as transferrin saturation (TS) >50% or >45%
      and serum ferritin (SF) >300 or >250 microg/ml in males and females,
      respectively. Subjects with increased TS and/or SF were re-tested and typed for
      HFE mutations C282Y and H63D. A total of 548 individuals had increased iron
      parameters at first testing. In total, 179/548 were available for retesting, and
      in 109 increased TS and/or SF were confirmed. Increased TS was confirmed in 25
      individuals, among whom three were C282Y homozygotes and six were compound
      heterozygotes for C282Y and H63D. Increased TS was more frequent in northern
      Italy than in southern regions. In individuals with increased TS and/or SF, the
      frequency of C282Y and H63D was 0.13 and 0.21 in northern-Italy versus 0.05 and
      0.45 in southern Italy (P=0.004 for H63D). Nine out of 10 individuals carrying
      hemochromatosis-associated genotypes (including compound heterozygosity for C282Y
      and H63D) originated from northern regions. Among controls, the allelic
      frequencies of C282Y and H63D were 0.037 and 0.16 in the northern regions and
      0.015 and 0.16 in the southern regions. In conclusion, over one-third of
      individuals with persistently altered TS carried hemochromatosis-associated
      genotypes, confirming that a diagnostic approach based on TS and genotyping of
      selected cases may represent a viable screening procedure.

PMID- 14671619
TI  - Normoblastosis, a murine model for ankyrin-deficient hemolytic anemia, is caused
      by a hypomorphic mutation in the erythroid ankyrin gene Ank1.
AB  - Ankyrin deficiency is one of the most common causes of hereditary spherocytosis
      in humans. A spontaneous mutation, normoblastosis (Ank1nb), discovered in 1969 in
      a mouse stock maintained at the Jackson Laboratory, provides an important animal
      model for these human ankyrin-deficient anemias. Study of this model has led to
      the finding of multiple isoforms of Ank1 as well as Ank1nb-related pathology in
      nonerythroid tissues. To enhance the usefulness of this model, we have identified
      the Ank1nb mutation as the deletion of a guanosine residue in exon 36 of the
      erythroid ankyrin gene (Ank1). This results in a frame shift that introduces a
      stop 13 codons downstream and predicts a 157 kDa nb-ankyrin lacking the
      regulatory domain but including intact membrane- and spectrin-binding domains. By
      epitope scanning on immunoblots, we show that a previously reported protein
      (p150) found in nb reticulocytes is the predicted nb-ankyrin. Existing evidence
      indicates that this protein is functional, making the normoblastosis mutation a
      hypomorph rather than a null as originally thought. The nb-ankyrin provides an
      explanation for the milder phenotype displayed by nb/nb animals relative to the
      murine spectrin-deficient anemias, spherocytosis (Spna1(sph), Spna1(sph-1J),
      Spna1(sph-2BC), Spna1(sph-DEM)) and jaundiced (Spnb1(ja)), and suggests that
      truncated ankyrins could be useful in gene replacement therapy.

PMID- 14671620
TI  - Refractory cold agglutinin-immunohaemolytic anaemia associated to marginal zone
      lymphoma responding to rituximab.
AB  - Cold agglutinin immunohaemolytic anaemia (CAIA) responds poorly to standard
      treatment. We report a case of marginal zone lymphoma complicated by CAIA that
      responded to rituximab after failing to respond to corticosteroids and
      chlorambucil.

PMID- 14671621
TI  - Rejection of the second allogeneic graft in a child with Fanconi anemia reversed
      by antilymphocyte globulin and donor lymphocyte infusion.
AB  - Rejection after allogeneic bone marrow transplantation for Fanconi anemia (FA) is
      a complication with a high risk of mortality. We describe a patient who,
      following a second episode of rejection after a second allogeneic stem cell
      transplantation, was successfully treated with antilymphocyte globulin, followed
      by donor lymphocyte infusion. At three and a half years after donor lymphocyte
      infusion, she is alive with a Karnofsky score of 90%. Her molecular chimerism is
      of donor origin. Thus, donor lymphocyte infusion can be considered as a therapy
      option for rejection after allogeneic bone marrow transplantation for FA.

PMID- 14671622
TI  - Elevated serum angiogenin in multiple myeloma.

PMID- 14671623
TI  - Erythropoietic recovery during treatment with darbepoietin-alpha after impaired
      rHuEPO response to anemia in two patients with osteomyelofibrosis after
      peripheral blood stem cell transplantation.

PMID- 14671624
TI  - Perspective study on pamidronate in stage I multiple myeloma.

PMID- 14671630
TI  - Efficacy and toxicity of low-dose escalating donor lymphocyte infusion given
      after reduced intensity conditioning allograft for multiple myeloma.

PMID- 14671631
TI  - CD87 (urokinase-type plasminogen activator receptor), function and pathology in
      hematological disorders: a review.
AB  - The analysis of CD87 (urokinase-type plasminogen activator receptor - uPAR)
      expression has a potential role in the diagnostic or prognostic work-up of
      several hematological malignancies, particularly acute leukemia and multiple
      myeloma. The distribution of CD87 in acute myeloid leukemia (AML) varies
      according to the FAB subtype (highest expression in M5 and lowest in M0).
      Functionally, it is conceivable that the expression of CD87 could contribute to
      the invasive properties of the leukemic cells towards the skin and mucosal
      tissues as reflected by the clinical behavior of CD87 high cases. The lack of or
      weaker expression of CD87 on blast cells from ALL patients supports the concept
      that CD87 investigation might help in the distinction of AMLs from lymphoid
      malignancies. Among lymphoproliferative disorders, the expression of CD87 is
      exclusively found in pathological plasma cells. Since plasma cells also coexpress
      some adhesion molecules such as CD138 and CD56, this observation is consistent
      with the capacity of these cells to home in the bone compartment. High levels of
      soluble uPAR appear to represent an independent factor predicting worse prognosis
      and extramedullary involvement in multiple myeloma.

PMID- 14671632
TI  - Relationship between the mutational status of VH genes and pathogenesis of
      diffuse large B-cell lymphoma in Richter's syndrome.
AB  - Patients with chronic lymphocytic leukemia (CLL) may develop diffuse large B-cell
      lymphoma (DLBL), also known as Richter's syndrome. Mutational status of
      immunoglobulin (Ig) heavy-chain variable region (VH) genes have prognostic impact
      in CLL. Patients with mutated VH genes have a stable disease, whereas patients
      with unmutated VH gene have more aggressive disease. The mutational status of
      CLLs that transform to DLBL is unknown. To reveal whether Richter's syndrome
      occurs in CLLs with mutated or unmutated VH genes, we have performed mutational
      analysis on serial specimens from eight patients. CLL and DLBL tumorclones were
      identical in five cases and they were different in three cases. Six CLLs
      expressed unmutated and two cases expressed mutated VH genes. In five of the six
      unmutated CLLs, the DLBL clones evolved from CLL tumorclones and the VH genes
      expressed by DLBLs were also unmutated. In one unmutated and two mutated CLLs,
      the DLBLs expressed mutated VH genes, but in these three cases the DLBL
      tumorclones developed as independent secondary neoplasm. These results suggest
      that Richter's syndrome may develop in both mutated or unmutated CLLs, but clonal
      transformation of CLL to DLBL occur only in the unmutated subgroup of CLL.

PMID- 14671633
TI  - Impairment of heart rate variability control during arsenic trioxide treatment
      for acute promyelocytic leukemia.

PMID- 14671634
TI  - Recombinant human erythropoietin induces intussusceptive microvascular growth in
      vivo.
AB  - The role of erythropoietin (Epo) in angiogenesis has not been completely
      clarified. Epo induces endothelial cell proliferation and migration and
      stimulates angiogenesis on rat aortic rings in vitro and in vivo in the chick
      embryo chorioallantoic membrane (CAM) assay. The aim of the present study was to
      evaluate the ultrastructural aspects of angiogenesis in the CAM vasculature after
      recombinant human Epo (rHuEpo) exposure. The results demonstrated that after
      rHuEpo stimulation, the generation of new blood vessels occurred more frequently
      following an intussusceptive microvascular growth (IMG) mechanism. We have
      performed our experiments between days 8 and 12 of incubation, that is, when in
      the normal condition the capillary network expands mainly by IMG, and because it
      is generally accepted that implants made from days 8 to 10 are strongly
      angiogenic. This response is peculiar of rHuEpo, because it is abolished when an
      Epo-blocking antibody was coadministered with Epo.

PMID- 14671635
TI  - Impact of cytogenetics on the prognosis of adults with de novo AML in first
      relapse.
AB  - Karyotype is an important prognostic factor in patients with newly diagnosed
      acute myeloblastic leukaemia (AML). The prognostic value of cytogenetics on the
      outcome of patients with AML in relapse has not yet been well defined. We
      analysed the clinical outcome of 152 patients with de novo, chemotherapy-treated
      AML in first relapse according to the cytogenetic classification of the United
      Kingdom Medical Research Council. The rate of second complete remission (CR) (88,
      64 and 36%) and the probability of survival at 3 years (43, 18 and 0%) were
      significantly different between the favourable, intermediate and adverse
      cytogenetic risk groups, respectively. Compared to the favourable group, the
      relative risk (RR) of death (multivariate analyses) was 2.6 (confidence interval
      (CI): 1.5-4.4, P<0.001) for the intermediate and 3.7 (CI: 1.7-7.9, P=0.001) for
      the adverse group. The prognostic value of the duration of first CR was confirmed
      (RR of death: 2.0 (CI: 1.0-4.0) for each additional year in first CR), whereas
      the FLT3 mutation obtained at diagnosis did not markedly influence the outcome of
      patients with AML in relapse. In conclusion, our results indicate that both
      karyotype and the duration of first CR are independent prognostic factors for
      patients with de novo AML in first relapse.

PMID- 14671636
TI  - A note on myeloperoxidation index and its correlation to the biomarker, urine
      trans, trans-muconic acid level, in the subjects occupationally exposed to
      benzene.

PMID- 14671637
TI  - Flavopiridol: where do we stand in chronic lymphocytic leukemia?

PMID- 14671638
TI  - Malignant hematopoietic cell lines: in vitro models for the study of MLL gene
      alterations.
AB  - Human tumor cell lines are powerful tools for investigating basic and applied
      aspects of cell biology. Leukemia-lymphoma cell lines have been instrumental in
      the cytogenetic and molecular analysis of recurring chromosome rearrangements,
      notably translocations and inversions, thus illuminating the pathogenesis of
      hematological malignancy. Chromosomal translocations targeting the MLL gene at
      11q23 have come to represent a paradigm in acute leukemias. These translocations
      result in the in-frame joining of the MLL gene with a partner gene to generate
      unique fusion proteins of putatively novel function. More than 30 partner genes
      that participate with MLL in the more than 60 known 11q23 translocations have
      been reported. Cell lines provide territory to both explore the detailed
      structures of 11q23 translocations and investigate the leukemogenic activities of
      MLL fusion proteins. We review here the leukemia cell lines that have been
      described to carry 11q23 translocations and MLL fusion genes. Except for the
      t(10;11)(p12;q23), each of the following relatively frequent 11q23/MLL
      translocations is represented by one or more cell lines: 16 cell lines with
      t(4;11)(q21;q23), two cell lines with t(6;11)(q27;q23), seven cell lines with
      t(9;11)(p22;q23), and eight cell lines with t(11;19)(q23;p13). For each of three
      rare translocations, one cell line has been reported: t(5;11)(q15;q23),
      t(11;16)(q23;p13), and t(X;11)(q13;q23). Of these 36 cell lines with 11q23
      translocations, 17 have been made available to us; we confirmed the occurrence of
      the alterations reported in these cell lines at the chromosomal and/or gene
      level. A second type of MLL gene alteration is the partial tandem duplication
      (PTD), which occurs in acute myeloid leukemia (AML). We found four AML cell lines
      with an MLL PTD; one acute lymphoblastic leukemia-derived cell line was reported
      to show a partial nontandem duplication. Finally, a third rearrangement involves
      intrachromosomal amplification of the unrearranged MLL gene leading to multiple
      copies of the gene and (presumably) increased expression. Three cell lines
      carrying such MLL amplifications have been described. The availability of these
      cell lines as model systems provides the opportunity to explore the altered
      expression or functions of MLL genes and their partners in oncogenesis.

PMID- 14671639
TI  - High expression of the sister-chromatid separation regulator and proto-oncogene
      hSecurin occurs in a subset of myeloid leukaemias but is not implicated in the
      pathogenesis of aneuploidy.
AB  - Aneuploidy is considered to play an important role in the pathogenesis of
      malignancies. We were interested whether abnormalities of the sister-chromatid
      separation regulator and proto-oncogene hSecurin occurred in myeloid leukaemias,
      and whether such abnormalities correlated with aneuploidy. The expression of
      hSecurin was assessed by real-time quantitative PCR in samples from patients with
      acute myeloid leukaemia (AML, n=70), chronic myeloid leukaemia (CML) in chronic
      phase (CP, n=20) or blast phase (BP, n=12), and granulocytes as well as
      mononuclear cells (MNCs) from healthy donors (n=21). Median hSecurin expression
      in AML with normal karyotypes was not significantly different from AML showing
      aneuploidy, CML BP or cells from healthy donors. However, hSecurin expression in
      CML CP was significantly increased compared to AML with normal karyotypes (1.82
      fold; P<0.001), CML BP (3.18-fold; P<0.001), MNCs (3.17-fold; P<0.001) and
      granulocytes (2.69 fold; P<0.001) from healthy donors. Mutations in the coding
      region of hSecurin were not detected. These results do not support a major role
      of hSecurin in the development of aneuploidy in myeloid leukaemias. However, high
      expression of hSecurin may be of pathogenetic relevance in a subset of patients
      with regard to its potential to stimulate angiogenesis and to interact with the
      DNA-damage response pathway.

PMID- 14671640
TI  - Role of curcumin and the inhibition of NF-kappaB in the onset of chemotherapy
      induced mucosal barrier injury.
AB  - The inhibition of nuclear factor kappa B (NF-kappaB) by, for instance, curcumin
      is becoming an important new approach in combination with chemotherapy or
      irradiation for the treatment of a variety of cancers including haematological
      malignancies. A dose-limiting side effect of anticancer therapy in the
      gastrointestinal tract is mucosal barrier injury. It is hypothesised that mucosal
      barrier injury is initiated and amplified by proinflammatory-and NF-kappaB
      regulated mediators. Therefore, the effect of NF-kappaB inhibition was studied in
      the onset of mucosal barrier injury. In response to cytostatic drug treatment
      (arabinoside cytosine (Ara-C) and methotrexate (MTX)), NF-kappaB was activated in
      intestinal epithelial cells (IEC-6) resulting in an NF-kappaB-related induction
      of tumour necrosis factor alpha and monocyte chemoattractant protein-1. NF-kappaB
      inhibition increased the susceptibility of IEC-6 cells to Ara-C as well as MTX
      induced cell death when obtained by the addition of caffeic acid phenethyl ester
      (CAPE), but not using curcumin. In an animal model for MTX-induced mucosal
      barrier injury, the induction of NF-kappaB-related cytokines and chemokines was
      detected upon treatment with MTX. Despite increased susceptibility shown in
      vitro, the inhibition of NF-kappaB resulted in a partial amelioration of villous
      atrophy normally seen in the small intestine upon MTX treatment. These results
      show that the inhibition of NF-kappaB does not increase intestinal side effects
      of the anticancer treatment, suggesting a safe use of curcumin and CAPE in
      combination with anticancer treatment.

PMID- 14671641
TI  - Simultaneous detection of the immunophenotypic markers and genetic aberrations on
      routinely processed paraffin sections of lymphoma samples by means of the FICTION
      technique.
AB  - Disciplines such as morphology, immunophenotyping and genetics widely contributed
      over decades to the understanding of the cellular mechanisms of cancer. To obtain
      a greater insight into the complex processes of tumorigenesis, scientists have
      joined their efforts to combine many of the available techniques. Here, we report
      on the development of a FICTION (Fluorescence Immunophenotyping and Interphase
      Cytogenetics as a tool for the Investigation of Neoplasms) technique that allows
      a simultaneous detection of immunophenotypic markers and genetic aberrations on
      routinely processed lymphoma samples. As the antigen retrieval method seems to
      play an important role in the final results, we tested the pressure-cooking
      method at different times (2, 4 and 8 min) using three different buffers (EDTA,
      Tris-EDTA and citrate), resulting in improved sensitivity for the detection of
      both immunophenotypic markers and genetic aberrations. We also applied this
      method to different types of lymphoma using double immunofluorescence assays
      (including CD30, CD20, CD8 monoclonal antibodies) and several fluorescence in
      situ hybridization probes to demonstrate that the FICTION technique could be
      easily applied on paraffin sections in different combinations for the diagnosis
      and research of cancer.

PMID- 14671642
TI  - Sustained molecular response with imatinib in a leukemic form of idiopathic
      hypereosinophilic syndrome in relapse after allograft.

PMID- 14671643
TI  - Effects of SET and SET-CAN on the differentiation of the human promonocytic cell
      line U937.
AB  - Human SET encodes a nuclear phosphoprotein with a highly acidic carboxyl
      terminus, forming a SET-CAN fusion gene in a patient with acute undifferentiated
      leukemia. SET is highly conserved between species and is ubiquitously expressed,
      suggesting a widespread biological role. Even though SET is involved in chromatin
      remodeling and transcriptional activation, its precise role in hematopoietic
      cells and the contribution of SET-CAN to leukemogenesis remains unknown. We
      determined the effect of tetracycline-regulatable expression of SET, a deletion
      mutant of SET, and SET-CAN on the human promonocytic cell line U937T. The
      expression of SET and SET-CAN inhibited proliferation of these cells. SET
      accomplishes this through the induction of the differentiation program, an effect
      that depends on the presence of its acidic domain. SET-CAN most likely inhibits
      growth by interfering with hCRM1, but it also partially blocks differentiation.
      Our results are the first demonstration of a potential role of SET in
      hematopoietic differentiation.

PMID- 14671644
TI  - Interleukin-3 receptor in acute leukemia.
AB  - Recent studies indicate that abnormalities of the interleukin-3 receptor (IL-3R)
      are frequently observed in acute myeloid leukemias (AMLs) and may contribute to
      the proliferative advantage of leukemic blasts. This review analyzes the
      evidences indicating that the IL-3R represents one of the target molecules
      involved in the stimulation of proliferation of AMLs, and the overexpression of
      the IL-3Ralpha chain may represent one of the mechanisms contributing to the
      development of a highly malignant leukemic phenotype. Furthermore, there is
      evidence that the IL-3Ralpha is a marker of leukemic stem cells, at variance with
      normal stem cells that are IL-3Ralpha-. Finally, the IL-3R may represent an
      important target for the development of new antileukemic drugs.

PMID- 14671645
TI  - Pegylated recombinant interferon alpha-2b vs recombinant interferon alpha-2b for
      the initial treatment of chronic-phase chronic myelogenous leukemia: a phase III
      study.
AB  - Recombinant interferon alpha-2b (rIFN-alpha2b) is an effective therapy for
      chronic-phase chronic myelogenous leukemia (CML). Polyethylene glycol-modified
      rIFN-alpha2b is a novel formulation with a serum half-life ( approximately 40 h)
      compatible with once-weekly dosing. This open-label, noninferiority trial
      randomized 344 newly diagnosed CML patients: 171 received subcutaneous pegylated
      rIFN-alpha2b (6 microg/kg/week); 173 received rIFN-alpha2b (5 million
      International Units/m2/day). Primary efficacy end point was the 12-month major
      cytogenetic response (MCR) rate (<35% Philadelphia chromosome-positive cells).
      Modified efficacy analysis included all MCRs >12 months, except for patients
      discontinuing treatment after 6 months and achieving an MCR on other salvage
      therapy. The MCR rates were 23% for pegylated rIFN-alpha2b vs 28% for rIFN
      alpha2b in the primary efficacy analysis and 26 vs 28% in the prospectively
      modified efficacy analysis. However, a significant imbalance in baseline
      hematocrit (HCT), a significant predictor of cytogenetic response (P=0.0001), was
      discovered: 51 (30%) patients treated with pegylated rIFN-alpha2b had low HCT
      (<33%) vs 33 (19%) rIFN-alpha2b-treated patients. Among patients with HCT >33%,
      the MCR rate was 33 vs 31%. The adverse event profile of weekly pegylated rIFN
      alpha2b was comparable to daily rIFN-alpha2b. Once-weekly pegylated rIFN-alpha2b
      is an active agent for the treatment of newly diagnosed CML with an efficacy and
      safety profile similar to daily rIFN-alpha2b, although statistical noninferiority
      was not demonstrated.

PMID- 14671647
TI  - Assessing hematopoietic chimerism after allogeneic stem cell transplantation by
      multiplexed SNP genotyping using microarrays and quantitative analysis of SNP
      alleles.
AB  - Single-nucleotide polymorphisms (SNPs) have the potential to be particularly
      useful as markers for monitoring of chimerism after stem cell transplantation
      (SCT) because they can be analyzed by accurate and robust methods. We used a two
      phased minisequencing strategy for monitoring chimerism after SCT. First,
      informative SNPs with alleles differing between donor and recipient were
      identified using a multiplex microarray-based minisequencing system screening 51
      SNPs to ensure that multiple informative SNPs were detected in each donor
      recipient pair. Secondly, the development of chimerism was followed up after SCT
      by sensitive, quantitative analysis of individual informative SNPs by applying
      the minisequencing method in a microtiter plate format. Using this panel of SNPs,
      we identified multiple informative SNPs in nine unrelated and in 16 related donor
      recipient pairs. Samples from nine of the donor-recipient pairs taken at time
      points ranging from 1 month to 8 years after transplantation were available for
      analysis. In these samples, we monitored the allelic ratios of two or three
      informative SNPs in individual minisequencing reactions. The results agreed well
      with the data obtained by microsatellite analysis. Thus, we conclude that the two
      phased minisequencing strategy is a useful approach in the following up of
      patients after SCT.

PMID- 14671648
TI  - Evaluation of STR informativity for chimerism testing--comparative analysis of 27
      STR systems in 203 matched related donor recipient pairs.
AB  - Chimerism analysis has become a routine method to document engraftment and also
      for detection of residual disease. PCR-based procedures using STR analysis,
      especially commercially available multiplex assays, are frequently used. However,
      these assays have been optimized for forensic purposes and do not necessarily
      fulfil all needs for chimerism analysis. To improve these analyses, data on the
      level of informativity of STR systems in the context of chimerism analysis would
      be helpful. We evaluated 27 STR markers for their informativity in 203 patients
      and their HLA-matched related donors. These STRs included 18 from different
      multiplex kits, whereas nine were selected from the literature or STR databases.
      The STR profiles were ranked from Type 1 (not informative) to Type 5 (best suited
      for chimerism analysis). According to this ranking, the informativity of the STR
      systems was found highly variable, ranging from 4.4 to 49.0% Type 5
      constellations. Among the most informative STRs were Penta E, SE33, D2S1338 and
      D18S51. Informativity of an STR was correlated with the degree of heterozygosity
      (r=0.86; P=0.0001), but not with the total number of alleles present. These data
      indicate that selection of suitable STR markers is important to improve
      diagnostics based on STR analysis.

PMID- 14671649
TI  - The p210BCR-ABL tyrosine kinase of chronic myeloid leukemia causes resistance to
      radio-induced apoptotic death by inhibiting the proapoptotic BAX gene.

PMID- 14671650
TI  - Design and standardization of PCR primers and protocols for detection of clonal
      immunoglobulin and T-cell receptor gene recombinations in suspect
      lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936.
AB  - In a European BIOMED-2 collaborative study, multiplex PCR assays have
      successfully been developed and standardized for the detection of clonally
      rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome
      aberrations t(11;14) and t(14;18). This has resulted in 107 different primers in
      only 18 multiplex PCR tubes: three VH-JH, two DH-JH, two Ig kappa (IGK), one Ig
      lambda (IGL), three TCR beta (TCRB), two TCR gamma (TCRG), one TCR delta (TCRD),
      three BCL1-Ig heavy chain (IGH), and one BCL2-IGH. The PCR products of Ig/TCR
      genes can be analyzed for clonality assessment by heteroduplex analysis or
      GeneScanning. The detection rate of clonal rearrangements using the BIOMED-2
      primer sets is unprecedentedly high. This is mainly based on the complementarity
      of the various BIOMED-2 tubes. In particular, combined application of IGH (VH-JH
      and DH-JH) and IGK tubes can detect virtually all clonal B-cell proliferations,
      even in B-cell malignancies with high levels of somatic mutations. The
      contribution of IGL gene rearrangements seems limited. Combined usage of the TCRB
      and TCRG tubes detects virtually all clonal T-cell populations, whereas the TCRD
      tube has added value in case of TCRgammadelta(+) T-cell proliferations. The
      BIOMED-2 multiplex tubes can now be used for diagnostic clonality studies as well
      as for the identification of PCR targets suitable for the detection of minimal
      residual disease.

PMID- 14671651
TI  - Influence of stochastics on quantitative PCR in the detection of minimal residual
      disease.

PMID- 14671655
TI  - Relation of sex steroid hormones to genital tissue structure and arousal: a
      sampling of manuscripts discussing endocrinologic sexual dysfunction.

PMID- 14671656
TI  - Downregulation of androgen, estrogen and progesterone receptor genes and protein
      is involved in aging-related erectile dysfunction.
AB  - We hypothesize that downregulation of sex hormone receptors (androgen, estrogen
      and progesterone receptors) is involved in aging-related erectile dysfunction. To
      test this hypothesis, we investigated the expression of sex hormone receptors in
      penile crura of aging rats. A total of 40 rats were divided into four groups
      based on age (6, 12, 18 and 24 months), and the erectile function was analyzed by
      the measurement of intracavernous pressure. Gene and protein expressions of sex
      hormone receptors were analyzed by RT-PCR and immunostaining, respectively. The
      mean intracavernous pressures of 6-, 12-, 18- and 24-month-old rats were 110.1,
      89.6, 73.5 and 42.7 cm H(2)O, respectively. Gene and protein expressions for
      androgen receptor, estrogen receptor-beta and progesterone receptor were present
      in similar levels in 6-, 12- and 18-month-old rat crura, but significantly lower
      or absent in 24-month-old crura. This is the first study to demonstrate that
      downregulation of sex hormone receptors in aging rat crura is associated with
      erectile dysfunction.

PMID- 14671657
TI  - Sex steroid hormones differentially regulate nitric oxide synthase and arginase
      activities in the proximal and distal rabbit vagina.
AB  - Nitric oxide synthase (NOS) and arginase have been shown to regulate nitric oxide
      (NO) production reciprocally in genital tissues. In animal models, NO is an
      important regulator of vaginal blood flow and vaginal wall contractility. In this
      study, we investigated the modulation of NOS and arginase activities by estrogens
      and androgens in the proximal and distal rabbit vagina. In intact control
      animals, total NOS activity was higher in the proximal (528+/-78 pmol/mg protein)
      than the distal (391+/-44 pmol/mg protein) vagina. However, arginase activity was
      higher in the distal (206+/-8 nmol/mg protein) than the proximal (64+/-5 nmol/mg
      protein) vagina. Ovariectomy enhanced NOS activity in the proximal but not distal
      vagina with concomitant decrease in arginase activity in both the proximal and
      distal vagina. In ovariectomized rabbits, replacement with 5alpha
      dihydrotestosterone (DHT) or Delta5-androstenediol (Adiol) increased NOS activity
      beyond that observed in ovariectomized rabbits receiving vehicle. In contrast,
      DHT and Adiol treatment reduced arginase activity more than that of the
      ovariectomized rabbits receiving vehicle. Testosterone exhibited inconsistent
      effects on NOS and arginase activity in the distal and proximal vagina. Estradiol
      replacement in ovariectomized animals reduced NOS activity in the proximal vagina
      down to levels that were comparable to intact control animals. However, estradiol
      positively modulated arginase activity in the distal vagina. Western blot
      analyses indicated that in the proximal vagina, neural NOS protein levels
      paralleled the changes observed in enzyme activity. These observations suggest
      that steroid hormones differentially regulate NOS and arginase activities of the
      proximal and distal regions of the vagina. Although estrogen treatment reduced
      total NOS activity in proximal vagina, estrogens are known to enhance vaginal
      blood flow. This paradoxical observation may be explained by differential
      regulation of n-NOS and e-NOS in the proximal and distal vagina. We suggest that
      changes in vaginal blood flow and compliance may depend on the endocrine status
      and the levels of circulating androgens and estrogens.

PMID- 14671658
TI  - Efficacy of DA-8159, a new PDE5 inhibitor, for inducing penile erection in
      rabbits with acute spinal cord injury.
AB  - DA-8159 is a pyrazolopyrimidinone derivative which exhibits potent and selective
      phosphodiesterase type 5 (PDE5) inhibition. The aim of this study was to
      investigate the effects of DA-8159 on inducing a penile erection in rabbits with
      an acute spinal cord injury (ASCI). DA-8159 was given either orally (1, 3, or 10
      mg/kg) or intravenously (0.1 or 0.3 mg/kg) to conscious male albino rabbits with
      a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or
      ischemic-reperfusion SCI rabbits. Erection was evaluated in a time-course manner
      by measuring the length of the uncovered penile mucosa. DA-8159 induced a dose
      dependent erection in both transection and ischemic-reperfusion ASCI rabbits. The
      efficacy of DA-8159 was potentiated by an intravenous injection of sodium
      nitroprusside, a nitric oxide donor. Potentiation of the effect by nitric oxide
      donor implies that DA-8159 can enhance the erectile activity during sexual
      arousal. These results suggest that DA-8159 may be useful for treating erectile
      dysfunction in patients with an SCI.

PMID- 14671659
TI  - What to learn about sildenafil in the treatment of erectile dysfunction from 3
      year clinical experience.
AB  - We retrospectively assessed the clinical uses and results of sildenafil in the
      treatment of erectile dysfunction (ED) in daily clinical practice from a cohort
      of 1658 subjects at a multispecialty medical center from 1999 to 2001 through a
      chart review, mailed questionnaire and telephone interview. The overall follow-up
      rate was 77.8% (1290/1658). The mean age was 63.8 y and ED duration was 3.4 y,
      and 44.6% of them had one or more concomitant conditions. The mean score of the
      International Index of Erectile Function erectile function domain was 12.7 in 314
      nonselective subjects, and 75% of them had moderate to severe ED. The average
      number of purchase-visits and tablets of sildenafil purchased was 2.27 and 10.8
      per person, respectively, and the prescription refill rate was 58.6%. Urology
      accounts for 91.4% of the specialties of prescribers. The response rate was
      72.0%, which was significantly lower in subjects with diabetes, ischemic heart
      disease and following radical pelvic surgery than those without. Subjects with
      psychogenic etiology had the highest response rate, while those following radical
      pelvic surgery the lowest. Of the nonresponders, 67% did not try the maximum dose
      of 100 mg and 71.1% bought no more than four tablets. Adverse events were
      reported in 20.1% of the subjects. No one discontinued the treatment because of
      the adverse events. Mortality occurred in 17 subjects and none was considered
      related to sildenafil use. In conclusion, sildenafil was effective and safe in
      the treatment of ED in clinical practice. Compared with clinical trials or
      prospective clinical practice based studies, lack of dose titration, less follow
      up visits and inadequate attempts before giving up were the main shortfalls in
      daily practice.

PMID- 14671661
TI  - Association between International Index of Erectile Function and axial penile
      rigidity in patients with erectile dysfunction.
AB  - We investigated the association between the International Index of Erectile
      Function (IIEF) and axial penile rigidity parameters in patients with erectile
      dysfunction (ED). A total of 516 male patients (491 patients with ED and 25
      patients without ED) were assessed using IIEF. Patients were assessed for axial
      penile rigidity (APR) using a digital inflection rigidometer. Mean age+/-s.d. was
      52.4+/-9.9 y. ED was mild in 11.4% of the patients, moderate in 40.1%, and severe
      in 48.5%. Regarding APR, the following was found: (1) no significant difference
      between patients who had a mild degree of ED and patients who had no ED (P>0.05);
      (2) a significant difference between patients with different degrees of ED
      (P<0.05 for each); (3) a significant association between overall presence of ED
      and low APR (P<0.05). IIEF score is associated with APR and can differentiate
      between patients with and without ED.

PMID- 14671660
TI  - Role of some vasoactive mediators in patients with erectile dysfunction: their
      relationship with angiotensin-converting enzyme and growth hormone.
AB  - The imbalance between vasoconstrictors and vasodilators may play an important
      role in the pathogenesis of erectile dysfunction (ED). A total of 36 patients
      with ED, organogenic [diabetic (n=12) and nondiabetic (n=12)] and psychogenic
      (n=12) etiology, and 12 healthy adult men as controls were included. The levels
      of endothelin-1 (ET-1), growth hormone (GH), angiotensin-converting enzyme
      activity (ACE), nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) were
      determined in the flaccid penis cavernosal blood of patients and in cubital blood
      of patients and controls. In psychogenic ED, systemic ACE activity was elevated
      compared to controls (P<0.05). In diabetic and nondiabetic ED patients, systemic
      levels of ET-1 (P<0.0001 for both) and ACE activity (P<0.01 and <0.05) were
      higher while GH (P<0.0001 and <0.001), NO (P<0.0001 for both) and cGMP (P<0.01
      for both) levels were lower compared to controls. In diabetic patients, systemic
      and cavernosal ET-1 levels (P<0.0001 for both) and cavernosal ACE activity levels
      (P<0.05) were significantly elevated while systemic and cavernosal NO (P<0.0001
      for both) and GH (<0.001 and <0.05) levels were declined compared to psychogenic.
      In nondiabetic patients, systemic and cavernosal ET-1 levels (P<0.0001 for both)
      were significantly elevated while systemic and cavernosal NO (P<0.0001 for both)
      and systemic GH levels (P<0.05) were declined compared to psychogenic. Systemic
      NO was positively correlated with GH in psychogenic (r=0.616, P<0.05), diabetic
      (r=0.583, P<0.05) and nondiabetic (r=0.615, P<0.05) patients and correlated
      positively with cGMP (r=0.605, P<0.05) but negatively with ACE activities (r=
      0.585, P<0.05) in diabetic patients. In conclusion, plasma levels of ET-1, ACE
      activities are elevated and associated with reduction of GH, NO and cGMP levels
      in the systemic and cavernous blood of ED patients. This disturbance may indicate
      endothelial dysfunction that may hind at their significance in the
      pathophysiology of ED.

PMID- 14671662
TI  - Hemochromatosis and sexual dysfunction.

PMID- 14671663
TI  - Factors associated with erectile dysfunction in male kidney transplant
      recipients.
AB  - A transversal study was carried out in order to evaluate the prevalence of
      erectile dysfunction (ED) in adult kidney transplant patients of our region
      (N=243), and to investigate the sociodemographic, analytic, and clinical factors
      associated with it. To evaluate ED, the Spanish five items version of the
      International Index of Erectile Function (IIEF-5) was employed. Sociodemographic,
      analytic, and clinical data, including 12 cardiovascular risk factors, were also
      collected. A total of 199 patients (82%) were included. The median age was 52 y
      (43-62 y); 106 patients (54.9%) presented with ED. Variables associated with ED
      were: higher age; longer time on dialysis prior to transplantation; higher
      comorbidity; presence of diabetes mellitus; had undergone prostatic surgery or
      peripheric artheriopathy; lower diastolic pressure; and some anti hypertensive
      drugs. Logistic Regression Model performed step by step showed (R(2)=0.52) that
      factors independently associated with ED were: age, time on dialysis previous to
      transplant, and peripheric artheriopathy.

PMID- 14671664
TI  - Human glans penis augmentation using injectable hyaluronic acid gel.
AB  - Although augmentation phalloplasty is not an established procedure, some patients
      still need enlargement of their penis. Current penile augmentation is girth
      enhancement of penile body by dermofat graft. We performed this study to identify
      the efficacy and the patient's satisfaction of human glans penis augmentation
      with injectable hyaluronic acid gel. In 100 patients of subjective small penis
      (Group I) and 87 patients of small glans after dermofat graft (Group II), 2 cm(3)
      of hyaluronic acid gel was injected into the glans penis, subcutaneously. At 1 y
      after injection, changes of glandular diameter were measured by tapeline.
      Patient's visual estimation of glandular size (Gr 0-4) and patient's satisfaction
      (Grade (Gr) 0-4) were evaluated, respectively. Any adverse reactions were also
      evaluated. The mean age of patients was 42.2 (30-70) y in Group I and 42.13 (28
      61) y in Group II. The maximal glandular circumference was significantly
      increased compared to basal circumference of 9.13+/-0.64 cm in Group I (P<0.01)
      and 9.49+/-1.05 cm in Group II (P<0.01) at 1 y after injection. Net increase of
      maximal glandular circumference after glans augmentation was 14.93+/-0.80 mm in
      Group I and 14.78+/-0.89 mm in Group II. In patient's visual estimation, more
      than 50% of injected volume was maintained in 95% of Group 1 and 100% of Group
      II. The percentage of postoperative satisfaction (Gr 4, 5) was 77% in Group 1 and
      69% in Group II. There was no abnormal reaction in area feeling, texture, and
      color. In most cases, initial discoloration by glandular swelling recovered to
      normal within 2 weeks. There were no signs of inflammation and no serious adverse
      reactions in all cases. These results suggest that injectable hyaluronic acid gel
      is a safe and effective material for augmentation of glans penis.

PMID- 14671665
TI  - Treatment satisfaction in patients with erectile dysfunction switching from
      prostaglandin E(1) intracavernosal injection therapy to oral sildenafil citrate.
AB  - Treatment satisfaction, subanalysed by demographic variables, was evaluated in
      patients switching from successful intracavernosal prostaglandin E(1) (PGE(1))
      therapy to oral sildenafil citrate. The validated Erectile Dysfunction Inventory
      of Treatment Satisfaction questionnaire was administered at the end of PGE(1)
      therapy and after 12 weeks of sildenafil treatment in a multicentre, open-label
      study. Men with erectile dysfunction (n=176) who were switched from stable PGE(1)
      therapy to sildenafil (25-100 mg) were equally satisfied with onset of action,
      duration of action, and confidence in ability to engage in sexual activity, but
      expressed greater overall treatment satisfaction with sildenafil (P<0.01), better
      ease of use (P<0.001), naturalness of erectile process (P<0.001), and intention
      to continue treatment (P<0.001). Partners (n=32) were overall more satisfied with
      sildenafil (P<0.05), and their responses correlated with patient satisfaction
      (r=0.68). Compared with PGE(1) injection, these data suggest that patients may be
      less likely to discontinue taking sildenafil treatment for their erectile
      dysfunction.

PMID- 14671666
TI  - Opposite effect of acute and subchronic treatments with Ferula hermonis on
      copulatory behavior of male rats.
AB  - Sexually potent and sluggish/impotent male rats were orally treated with an
      extract of Ferula hermonis (30 and 60 mg/kg). The acute administration stimulated
      sexual motivation in potent rats and improved copulatory performance in
      sluggish/impotent rats. This last effect was elicited only by the higher dose,
      which, in parallel, increased serum testosterone levels in rats. On the contrary,
      when the extract was subchronically administered (10 days) a marked reduction in
      the percentage of rats achieving ejaculation was detected, together with a
      general impairment of the copulatory pattern. Furthermore, the repeated
      administration of the extract (6 mg/kg/day for 10 days) resulted in a significant
      reduction of testosterone levels in comparison with controls. The present results
      discourage a repeated assumption of F. hermonis, while suggesting its acute
      administration to improve the performance in sexual dysfunctions.

PMID- 14671667
TI  - Augmentation of glans penis using injectable hyaluronic acid gel.
AB  - Recently, injectable hyaluronic acid gel has been widely used in soft-tissue
      augmentation. We performed this study to identify the feasibility of hyaluronic
      acid gel for the augmentation of the glans penis. In experiment I, 0.2 cm(3) of
      hyaluronic acid gel (HA) was injected into the dermis of the glans penis of 25
      New Zealand white rabbits via a 30 G needle. At 3, 7, 14, 30, and 90 days after
      injection, histological changes of glans were studied, respectively. In
      experiment II, 0.5 cm(3) of HA was injected into the dermis of the glans penis of
      14 Beagle dogs via a 27 G needle. At 6 months after injection, histological
      changes of the glans penis were also evaluated. At the time of autopsy, the lung,
      liver, and spleen were studied for systemic adverse reaction in each separate
      experiment. In experiment I, various sized cavities filled with amorphous
      basophilic materials were noted in the lamina propria and corpus spongiosum of
      the glans penis. All implants were positively stained on alcian blue. The
      intensity decreased in a time-dependent manner. Until 14 days, minimal
      inflammatory reactions were noted, but no signs of inflammation were identified
      at 90 days. With the gradual decrease of inflammation, fibrosis and deposition of
      collagen were noted. In experiment II, implants were well maintained at 6 months
      after injection in the lamina propria. Grade 1 of the inflammatory reaction was
      noted in one case. In both the experiments, all the specimens were free from any
      foreign body reaction and systemic adverse reactions. In conclusion, these
      results suggest that hyaluronic acid gel can be easily injected into the lamina
      propria of the glans penis and reside until 6 months. Injectable hyaluronic acid
      gel has a potential as a new bioimplant for the augmentation of the glans penis.

PMID- 14671669
TI  - Corporeal herniation after Nesbit plication with partial thickness shaving for
      congenital penile curvature.
AB  - A 24-year-old man with penile congenital curvature who underwent partial
      thickness tunical shaving and plication with absorbable suture presented 1 month
      after surgery with a mass at the base of the right corpus cavernosum at the level
      of the original plication. We believe that corporeal herniation after tunical
      shaving and plication must be considered a complication of the technique
      independent from the type of suture used for the plicatures and probably related
      both to the opening of plications of the albuginea before permanent adhesion of
      the tunical layers, and to the decreased resistance of the albuginea, probably
      because of excessive shaving.

PMID- 14671668
TI  - Topical administration of a novel nitric oxide donor, linear polyethylenimine
      nitric oxide/nucleophile adduct (DS1), selectively increases vaginal blood flow
      in anesthetized rats.
AB  - The aim of the present study was to test the effects of a topical administration
      of a novel nitric oxide donor, linear polyethylenimine-nitric oxide/nucleophile
      adduct (DS1), on vaginal blood flow and hemodynamics in rats. Laser Doppler
      flowmetry was used to measure blood flow changes following topical application of
      DS1 (0.3 or 1.5 mg in 0.15 ml saline) into the vagina of anesthetized Wistar
      rats. In vivo hemodynamic parameters were measured with Millar-tip-catheter
      placed in the left ventricle. DS1 (1.5 mg) increased vaginal blood flow by 191+/
      24, 226+/-22 and 166+/-23% of the baseline value (at 5, 15 and 30 min,
      respectively, after application) without affecting systemic blood pressure, heart
      rate and cardiac function. The increased vaginal blood flow following DS1
      application returned to baseline between 45 and 60 min. Thus, topical application
      of nitric oxide donors such as DS1 may be useful for the treatment of female
      sexual dysfunction that develops due to an impairment of local blood flow supply
      to the vaginal tissue.

PMID- 14671672
TI  - In vivo efficacy of folate-targeted lipid-protamine-DNA (LPD-PEG-Folate)
      complexes in an immunocompetent syngeneic model for breast adenocarcinoma.
AB  - Gene therapy utilizing lipid-based delivery systems holds tremendous promise for
      the treatment of cancer. However, due to the potential adverse inflammatory
      and/or immune effects upon systemic administration, treatments thus far have been
      predominantly limited to intratumoral or regional treatment. Previous studies
      from our group have demonstrated the antitumor efficacy of systemically
      administered, folate-targeted, lipid-protamine-DNA complexes (LPD-PEG-Folate)
      against breast cancer using an immunodeficient xenogenic murine model. In the
      current study, the antitumor efficacy of LPD-PEG-Folate in a syngeneic, immune
      competent, murine model of breast cancer was examined. In this model, the
      potential inflammatory or immune responses and their effects on systemic delivery
      can be addressed. The 410.4 murine breast adenocarcinoma cell line was initially
      evaluated in vitro for its interactions with LPD-PEG-Folate and control LPD-PEG
      formulations. Utilizing fluorescently labeled formulations and fluorescence
      activated cell sorting (FACS) analysis, a 1.6-fold enhancement of binding and
      internalization of LPD-PEG-Folate over LPD-PEG formulations was observed,
      suggestive of specific receptor interaction. Increased binding was manifested as
      5-26-fold increases in luciferase gene expression in 410.4 cell transfection when
      comparing LPD-PEG-Folate to LPD-PEG. Moreover, in vivo treatment of 410.4 breast
      tumors in BALB/c mice with i.v. injected LPD-PEG-Folate delivering the HSV-1
      thymidine kinase (TK) gene, in combination with gancyclovir treatment, resulted
      in a significant reduction in mean tumor volume (260.1 mm3) compared to the LPD
      PEG-TK (914.1 mm3), as well as the vehicle (749.7 mm3) and untreated (825.3 mm3)
      control groups (day 25, P<.019). In addition to a reduced tumor volume, LPD-PEG
      Folate-TK treatment also increased median survival from 25 days in the
      nontargeted LPD-PEG-TK groups to 31 days (P=.0011), which correlated with the
      termination of treatment. Together, these results demonstrate that in the context
      of a fully functional immune system, LPD-PEG-Folate-TK treatment possesses
      significant specific antitumor efficacy and the potential for further preclinical
      development.

PMID- 14671673
TI  - Comparison of different methods to assess the cytotoxic effects of cytosine
      deaminase and thymidine kinase gene therapy.
AB  - Dunning R3327 AT-1 rat prostate tumor cells were transfected with a double-fusion
      suicide gene (CDglyTK) that coded for the cytosine deaminase from E. coli and the
      thymidine kinase (TK) from HSV-1. The resulting cell line AT-1/CDglyTK was
      incubated with 10 and 20 microg/ml 5-FC or 0.25 microg/ml GCV, or both 5-FC and
      GCV 96 hours before harvest. The MTS assay detected cell viabilities of 50+/-5
      and 25+/-5% after 5-FC treatment, and 50+/-5% after GCV treatment. The dye
      exclusion and the colony-forming assay confirmed the data of the MTS assay with
      GCV (47+/-5 and 32+/-5%), but presented different results for the 5-FC
      incubation. We detected 100+/-1 and 85+/-5% viable cells after 10 microg/ml 5-FC,
      and 97+/-1 and 85+/-5% after 20 microg/ml 5-FC treatment, respectively. S-phase
      arrest in both suicide gene systems was noticeable and a significant increase in
      cell granularity was observed after incubation with GCV or GCV & 5-FC. This study
      demonstrates that 5-FC and the metabolized 5-FU act not only as genotoxic
      reagents, but also as RNA-directed agent, because of the recovery of the cells.
      On the other hand, a significant S-phase block could be observed after 24 hours
      incubation with GCV. This short time is enough to incorporate the genotoxic GCV
      metabolites in the nascent DNA to impair the cell cycle.

PMID- 14671674
TI  - Effective transfer of interleukin-12 gene to solid tumors using a novel gene
      delivery system, poly [D,L-2,4-diaminobutyric acid].
AB  - Delivery of the interleukin-12 (IL-12) gene to solid tumors is a promising
      anticancer therapy. Vectors are currently being developed to achieve safe and
      effective intratumoral delivery of the IL-12 gene. Poly [D,L-2,4-diaminobutyric
      acid] (PDBA) is a novel gene carrier that was recently described. The goal of
      this study was to use this gene delivery system for treatment of solid tumors. To
      determine the optimal conditions for transfection, established B16F10-melanomas
      in C57BL/6 mice were treated with intratumoral injection of the PDBA/plasmid
      luciferase (pLuc) complex. We determined that the optimal complex composition was
      50 microg/ml pLuc and 150 microg/ml PDBA. High levels of IL-12 protein were
      expressed in tumors after a single injection of PDBA/murine IL-12 (pmIL-12)
      complex, whereas serum levels of IL-12 in treated mice were below the limits of
      detection. IL-12 gene therapy with the PDBA system significantly inhibited tumor
      growth in comparison with the controls (P<.001). Moreover, both natural killer
      and cytotoxic T lymphocyte activities from draining lymph nodes of PDBA/pmIL-12
      treated mice were increased substantially in comparison with those of controls
      (P<.05). These results suggest that PDBA-mediated IL-12 gene therapy is a
      potential strategy for treatment of patients with solid tumors.

PMID- 14671675
TI  - Role of 4-1BB:4-1BB ligand in cancer immunotherapy.
AB  - The activation of T cells plays a central role in antitumor immunity. In order to
      activate naive T cells, two key signals are required. Signal one is provided
      through the T-cell receptor (TCR) while signal two is that of costimulation. The
      CD28:B7 molecules are one of the best-studied costimulatory pathways, thought to
      be the main mechanism through which primary T-cell stimulation occurs. However, a
      number of molecules have been identified which serve to amplify and diversify the
      T-cell response, following initial T-cell activation. These include the more
      recently described 4-1BB:4-1BB ligand (4-1BBL) molecules. 4-1BB:4-1BBL are a
      member of the TNFR:TNF ligand family, which are expressed on T cells and antigen
      presenting cells (APCs), respectively. Therapies utilizing the 4-1BB:4-1BBL
      signaling pathway have been shown to have antitumor effects in a number of model
      systems. In this paper, we focus on the 4-1BB:4-1BBL costimulatory molecules. In
      particular, we will describe the structure and function of the 4-1BB molecule,
      its receptor and how 4-1BB:4-1BBL costimulation has and may be used for the
      immunotherapy of cancer.

PMID- 14671676
TI  - The changes of hepatic metallothionein synthesis and the hepatic damage induced
      by starvation in mice.
AB  - Metallothionein (MT) is induced in the liver not only by heavy metals, but also
      by stress such as starvation. However, the meaning of the induced MT during
      starvation has never been clear. In this study, we investigated the relationship
      between changes in hepatic MT synthesis and the hepatic damage that occurs during
      starvation. MT synthesis was assessed by measuring MT contents and the expression
      of the MT gene in the liver. The hepatic damage was assessed by measuring
      glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT)
      activities in the serum. MT synthesis in the liver increased over the normal
      level by starvation, but decreased under the normal level by refeeding after
      starvation. Both GPT and GOT activities of the refeeding group were higher than
      those of the control group. However, MT synthesis increased by a subcutaneous
      injection with CdCl(2) (1 mg Cd /kg) at the same time as refeeding after
      starvation. At this point, GOT activity decreased until it reached the normal
      level. MT synthesis decreased by refeeding after starvation, and from the results
      found in this study, we proposed the hypothesis that the liver damage caused by
      refeeding after starvation might be due to the decrease in the synthesis of a
      sufficient amount of MT induced by metals.

PMID- 14671677
TI  - Evaluation of antiepileptic activity of aspirin in combination with newer
      antiepileptic lamotrigine in mice.
AB  - Neurotransmitters such as GABA, glutamate and prostaglandins mediate synaptic
      transmission and their modulation may play a role in the generation of seizures.
      Numerous studies implicate prostaglandins as potential modulators of seizure
      activity. This study was designed to assess the antiepileptic activity of aspirin
      and to investigate the potentiation of its activity in combination with a
      subconvulsive dose of lamotrigine. Graded doses of aspirin and lamotrigine were
      used in pentylenetetrazole (PTZ) and maximal electroshock (MES) seizure models in
      mice. To study the interaction of aspirin and lamotrigine, ED(25) doses of
      aspirin (250 mg/kg) and lamotrigine (1.5 mg/kg) were used in the two seizure
      models. Aspirin dose-dependently decreased the incidence of seizures in the PTZ
      model mice but did not show any effect in MES-model mice. ED(25) doses of aspirin
      and lamotrigine showed 100% protection of the PTZ seizure model. Aspirin alone in
      doses of 400 and 800 mg/kg and in combination decreased mortality in the PTZ
      model. Aspirin showed a significant anticonvulsant effect in PTZ seizure mode.
      Potentiation of the anticonvulsant effect of lamotrigine with aspirin was shown
      in the PTZ model, indicating that prostaglandins could play an important role in
      this seizure model.

PMID- 14671678
TI  - Novel complement C1 inhibitor BSF468248 does not improve brain damage after
      cortical vein occlusion.
AB  - BSF468248 is a novel potent complement C1 inhibitor. To determine whether
      BSF468248 is effective against focal cerebral ischemia, we evaluated the change
      of cerebral blood flow (CBF) and infarction volume using a photochemically
      induced cortical vein occlusion model in rats in blind studies. In 22 Wistar
      rats, two adjacent cortical veins were occluded by photochemical thrombosis and
      fiberoptic illumination under controlled anesthesia and ventilation. Just after
      the occlusion, BSF468248 or physiological saline was administrated. In the low
      dose study, a treatment group (n = 7) was administered BSF468248 1 mg/kg bolus
      and 1 mg/kg continuously for 30 min. The same volume of saline was given to a
      vehicle group (n = 5). In the high-dose study, a treatment group (n = 5) was
      administrated BSF468248 1 mg/kg bolus and 12 mg/kg continuously for 180 min. The
      same volume of saline was given to a vehicle group (n = 5). During the
      experiment, regional cerebral blood flow (rCBF) was measured in both the low-dose
      study (120 min) and the high-dose study (180 min). Seven days after the
      experiment, the animals were killed in order to evaluate the infarct volume. The
      rCBF at the end of the experiment showed a similar decrease in both the low-dose
      study (at 120 min: treatment group: 66.5 +/- 10.2%; vehicle group: 69.3 +/-
      10.2%) and the high-dose study (at 180 min: treatment group: 62.1 +/- 7.5%;
      vehicle group: 65.1 +/- 12.3%), with no significant differences (t-test). The
      infarct volume also showed no significant difference in either group of the low
      dose study (treatment group: 3.46 +/- 0.84 mm3; vehicle group: 3.56 +/- 1.40 mm3)
      or the high-dose study (treatment group: 2.27 +/- 0.43 mm3; vehicle group: 1.76
      +/- 0.31 mm3). Our study found that BSF468248 is not effective in improving the
      rCBF and the infarct volume following focal cerebral ischemia.

PMID- 14671679
TI  - Hypoglycemic effect of Hypoxis hemerocallidea corm (African potato) aqueous
      extract in rats.
AB  - Diabetes mellitus has been recognized as a clinical syndrome since ancient times,
      and remains a crippling global health problem today. It is a group of
      heterogeneous, autoimmune, hormonal and metabolic disorders, often accompanied by
      hypertension, hyperlipidemia and obesity. Current estimates suggest that
      approximately 150 million people worldwide suffer from diabetes mellitus. The
      present study was undertaken to examine the hypoglycemic effect of aqueous
      extract of Hypoxis hemerocallidea (family: Hypoxidaceae) corm (locally known as
      "African Potato") in normal (normoglycemic) and in streptozotocin (STZ)-treated,
      diabetic rats. Young adult, male Wistar rats weighing 250-300 g were used.
      Diabetes mellitus was induced in the group of diabetic test rats by
      intraperitoneal injections of STZ (90 mg/kg). In one set of experiments, graded
      doses of the aqueous extract of African Potato (100-800 mg/kg p.o.) were
      administered to 12-h fasted normal and diabetic rats. In another set of
      experiments, 800 mg/kg of African potato extract, a dose of the plant extract
      that produced maximal hypoglycemic effects in fasted normal and diabetic rats in
      our pilot experiments, was used. The hypoglycemic effect of this single dose was
      compared with those of insulin (5 micro U/kg s.c.) and glibenclamide (5 mg/kg
      p.o.) in 12-h fasted normal and diabetic rats. Following acute treatment,
      relatively moderate to high doses of African potato extract (100-800 mg/kg p.o.)
      produced dose-dependent, significant reductions (p < 0.05-0.001) in the blood
      glucose concentrations of fasted normal and diabetic rats. Similarly, insulin (5
      micro U/kg s. c.) and glibenclamide (5 mg/kg p.o.) produced significant
      reductions (p < 0.01-0.001) in the blood glucose concentrations of the fasted
      normal and diabetic rats. At a dose of 800 mg/kg, the plant extract caused 30.20%
      and 48.54% reductions in the blood glucose concentrations of fasted normal and
      STZ-treated diabetic rats, respectively. While it is likely that the hypoglycemic
      effect of the plant extract is largely due to its phytosterols and/or sterolin
      content, the exact mechanism of its hypoglycemic action is still obscure and will
      have to await further studies. However, the results of this experimental animal
      study indicate that African potato possesses hypoglycemic activity; and thus
      lends credence to the suggested folkloric use of the herb in the control and/or
      management of adult-onset, type 2 diabetes mellitus in some communities of South
      Africa.

PMID- 14671680
TI  - Pharmacokinetics of omeprazole in patients with liver cirrhosis and extrahepatic
      portal venous obstruction.
AB  - Omeprazole is frequently used in patients with cirrhosis of the liver to treat
      peptic ulcer disease. It is also used for the healing of mucosal lesions after
      endoscopic sclerotherapy of esophageal varices in cirrhosis and extraheptic
      portal vein obstruction (EHPVO). This study was carried out with the aim of
      determining the pharmacokinetics of omeprazole in different degrees of liver
      cirrhosis and in patients with EHPVO, compared with healthy volunteers. Ten
      healthy volunteers, 30 patients with cirrhosis of the liver, divided into 3
      groups of 10 depending on severity (according to Child-Pugh classification A, B
      and C) and ten patients with EHPVO participated in the study. The subjects
      received an omeprazole 20 mg capsule after an overnight fast. Blood samples were
      collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 6, 9 and 24 h after drug administration.
      Omeprazole level in plasma was estimated by reverse-phase high performance liquid
      chromatography (HPLC). The elimination half-life was significantly (p < 0.05)
      increased to 2.38 +/- 0.16, 3.26 +/- 0,12, 3.58 +/- 0.31 and 2.59 +/- 0.22 h in
      patients with different grades of cirrhosis (A, B and C) and also in patients
      with EHPVO, respectively, compared with 1.054 + 0.10 h in healthy volunteers. A
      similar significant increase (p < 0.05) was observed in the AUC(0alpha), while
      C(max) was significantly increased to 400.40 +/- 27.89 and 602 +/- 55.13 ng/ml in
      only grade C cirrhosis patients and EHPVO patients, compared with 303.5 +/- 36.42
      ng/ml in healthy volunteers. No significant difference was observed in T(max). It
      was concluded that the metabolism of omeprazole was significantly impaired in
      both liver cirrhosis and EHPVO in comparison with healthy volunteers.

PMID- 14671681
TI  - Relative bioavailability and bioequivalence of a newly developed fixed
      combination sachet of acetylsalicylic acid and pseudoephedrine compared with a
      preliminary combination.
AB  - Acetylsalicylic acid (ASA) and pseudoephedrine (PSE) are often administered
      together for the treatment of symptoms of the common cold, i.e., nasal
      congestion, runny nose, sore throat and headache. Based on this fact we developed
      a fixed combination of 500 mg ASA and 30 mg PSE, the recommended doses for both
      drugs for treating symptoms of the common cold, as granulate to be dissolved in
      water for administration. The purpose of this open, randomized, three-factorial
      (three-treatment, three-period, six-sequence) Latin Square clinical study was to
      investigate the relative bioavailability of ASA and PSE as well as the
      establishment of bioequivalence after single administration of the fixed
      combination (final formulation for approval) of 500 mg ASA/30 mg PSE*HCl and the
      preliminary formulation of this combination. Pharmacokinetic characteristics
      AUC(norm) and C(max,norm) of ASA, its metabolite SA, and PSE, were determined as
      measure of rate and extent of absorption of the two formulations. The treatment
      ratios final/preliminary formulation and their corresponding 90% confidence
      intervals were calculated to establish bioequivalence. Additionally, descriptive
      statistics were calculated for the parameters t(max), t((1/2)), and mean
      residence time (MRT). In total, data from 18 healthy male volunteers were
      included in the pharmacokinetic evaluation. The primary target parameters were
      analyzed using an analysis of variance (ANOVA) after logarithmic transformation
      of the data. Confidence intervals of 90% were calculated for the geometric means
      of ratios using the mean square error term of the ANOVA. Bioequivalence criteria
      were fulfilled for AUC(norm) and C(max,norm). Geometric means of individual
      ratios of AUC(norm) and of C(max,norm) showed equal bioavailability of the new
      formulation compared with the preliminary. Furthermore, a relative
      bioavailability of approximately 100% of the preliminary formulation was shown
      for the newly developed formulation for all parameters. The parameters t(max),
      t((1/2)), and MRT showed comparable results for ASA, SA, and PSE, respectively,
      in both formulations. The supplementary evaluation for the non-normalized
      original parameters AUC and C(max) also revealed bioequivalence. For the newly
      developed formulation, the arithmetic means of the parameters AUC and C(max) for
      PSE were 1040.66 mg/h*l and 134.52 mg/l, for SA 142.28 mg/h*l and 30.34 mg/l,
      respectively. The median t(max) values were 0.67 h for PSE and 0.92 h for SA.
      Both treatments were safe and well tolerated.

PMID- 14671682
TI  - Irinotecan (CPT-11) in metastatic colorectal cancer patients resistant to 5
      fluorouracil (5-FU): a phase II study.
AB  - The efficacy and toxicity of irinotecan (CPT-11) 350 mg/m(2) i.v. once every 3
      weeks was assessed in 60 patients with advanced colorectal cancer (CRC) showing
      failure to 5-fluorouracil (5-FU) treatment. The overall objective response rate
      was 13.6% (1 complete response and 4 partial responses) and 25 patients (42.4%)
      showed stable disease; the median time to disease progression was 4.4 months and
      the median survival was 10.5 months. The main non-hematological toxicities were
      alopecia (80.3% of patients), diarrhea (75.0%), and nausea/vomiting (71.7%);
      neutropenia was the main hematological toxicity. Grade 3 or 4 diarrhea appeared
      in 21 of 131 cycles (16.1%), whereas grade 3 or 4 neutropenia appeared in 78
      cycles (25.0%). In conclusion, the present phase II study confirms that CPT-11
      350 mg/m(2) every 3 weeks is active and well tolerated as second-line
      chemotherapy for CRC in 5-FU resistant patients.

PMID- 14671683
TI  - Efficacy and tolerability of the hormone replacement drug estradiol
      valerate/levonorgestrel in the treatment of menopausal syndrome in Thai women.
AB  - A prospective, open, single-center, uncontrolled phase IV study examined the
      efficacy and tolerability of a 6-month oral sequential hormone replacement
      therapy (estradiol valerate and levonorgestrel; Klimonorm in 50 outpatient peri-
      and postmenopausal Thai women. The clinical effectiveness of the drug was
      demonstrated by a rapid alleviation of the classical vasomotor menopausal
      complaints and a favorable effect on lipid metabolism. A rapid reduction in
      climacteric complaints ranging up to the complete absence of symptoms was
      achieved during the first 3 months of treatment. The positive effect on lipid
      metabolism was demonstrated by a clear reduction in total cholesterol and
      triglycerides as well as a slight reduction in the LDL fraction and a significant
      increase in the HDL fraction. The therapy resulted in stabilization of the cycle
      length. Cycles with regular withdrawal bleeding periods lasting 3 to 4 days with
      mostly mild intensity were restored in most of the women. The thickness of the
      endometrium measured sonographically did not change significantly. The drug was
      safe and well tolerated by most of the women. There were no clinically
      significant changes in body weight, blood pressure, hematological tests, and
      other laboratory parameters. Compliance was very good with a dropout rate due to
      undesirable side effects of only 5%.

PMID- 14671684
TI  - Gateways to clinical trials.
AB  - Gateways to Clinical Trials is a guide to the most recent clinical trials in
      current literature and congresses. The data in the following tables has been
      retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R),
      the drug discovery and development portal, http://integrity.prous.com. This issue
      focuses on the following selection of drugs: 3,4-DAP; Adefovir dipivoxil, ADL-10
      0101, alefacept, alemtuzumab, alosetron hydrochloride, ALT-711, aprepitant,
      atazanavir sulfate, atlizumab, atvogen; Bortezomib; CETP vaccine, clevudine,
      crofelemer; DAC:GLP-1, darbepoetin alfa, decitabine, drotrecogin alfa
      (activated), DX-9065a; E-7010, edodekin alfa, emivirine, emtricitabine,
      entecavir, erlosamide, erlotinib hydrochloride, everolimus, exenatide;
      Fondaparinux sodium, frovatriptan, fulvestrant; Gemtuzumab ozogamicin, gestodene;
      Homoharringtonine, human insulin; Imatinib mesylate, indiplon, indium 111 (111In)
      ibritumomab tiuxetan, inhaled insulin, insulin detemir, insulin glargine,
      ivabradine hydrochloride; Lanthanum carbonate, lapatinib, LAS-34475,
      levetiracetam, liraglutide, lumiracoxib; Maxacalcitol, melagatran, micafungin
      sodium; Natalizumab, NSC-640488; Oblimersen sodium; Parecoxib sodium, PEG
      filgrastim, peginterferon alfa-2(a), peginterferon alfa-2b, pexelizumab,
      pimecrolimus, pleconaril, pramlintide acetate, pregabalin, prucalopride; rAHF
      PFM, Ranelic acid distrontium salt, ranolazine, rDNA insulin, recombinant human
      soluble thrombomodulin, rhGM-CSF, roxifiban acetate, RSD-1235, rubitecan,
      ruboxistaurin mesilate hydrate; SC-51, squalamine; Tegaserod maleate,
      telbivudine, tesaglitazar, testosterone gel, tezosentan disodium, tipranavir;
      Vatalanib succinate; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan;
      Zoledronic acid monohydrate.

PMID- 14671685
TI  - Cracking in a vitrification solution during cooling or warming does not effect
      growth of cryopreserved mint shoot tips.
AB  - No obvious decrease in viability or in the ability of mint shoot tips to develop
      into a shoot occurred during vitrification when the external glass cracked upon
      either cooling or warming. Samples within semen straws did not show a decrease in
      survival over three cycles of cooling and warming either in the presence or
      absence of cracking. No physical defects were visible in treated shoot tips.
      Cracking of the external glass formed from PVS2 did not obviously influence shoot
      tip survival in mint species.

PMID- 14671686
TI  - Multivariate metabolic profiling using 1H nuclear magnetic resonance spectroscopy
      of freeze-tolerant and freeze-intolerant earthworms exposed to frost.
AB  - Individuals of the freeze-tolerant earthworm, Dendrobaena octaedra, and four
      freeze-intolerant earthworm species (Dendrodrilus rubidus, Aporrectodea icterica,
      A. caliginosa, and A. longa) were frozen at -2 degree C. Control earthworms were
      exposed to +2 degree C. 1H nuclear magnetic resonance spectroscopy-based
      metabolic profiling in combination with multivariate pattern recognition methods
      (metabonomics) was used to produce a cross-species comparison. Several
      biochemical changes were detected as a result of freezing in all worm species,
      including an increase in relative free alanine concentrations, and an apparent
      conversion of adenosine to inosine. It was also possible to determine a number of
      biochemical changes that were unique to the freeze-tolerant species, D. octaedra.
      The most obvious difference was that, although all species showed an increase in
      glucose concentrations, the increase was largest in D. octaedra, and was coupled
      with a concomitant decrease in glycogen. This confirms that--like previously
      studied freeze-tolerant earthworm species--tolerance is effected by rapid glucose
      production from glycogen reserves. An additional difference noted was that
      succinate increased in all species on freezing, but the increase was least in D.
      octaedra. Furthermore there was no lactate accumulation in D. octaedra, whereas
      three of the other four species accumulated lactate. This indicates that anoxic
      metabolism was lowest in the freeze-tolerant species.

PMID- 14671687
TI  - Donor liver preservation and stimulation of adhesion molecules : cold
      preservation initiates the cascade.
AB  - BACKGROUND: Pro-inflammatory adhesion molecules (including ICAM-1, E-Selectin)
      are important in clinical hepatic ischaemia and reperfusion injury. The
      initiating factors remain to be fully elucidated. METHODS: Needle biopsies taken
      during and after donor liver preservation were studied in 28 cases by
      immunohistochemical methods. Human responder cell cultures were exposed to the
      effluent cold storage solution after liver preservation in a further 10
      transplants. RESULTS: Increased ICAM-1 staining was seen at the end of cold
      storage compared to baseline (P less than 0.01), whilst reperfusion caused
      further increase (P less than 0.001). The storage solutions stimulated ICAM-1 and
      E-Selectin expression in responder cells in vitro as a bioassay (P less than 0.01
      in each case). CONCLUSIONS: Liver harvesting and cold storage can initiate
      adhesion molecule expression even before reperfusion in the recipient.

PMID- 14671688
TI  - Studies on the toxicity of dimethyl sulfoxide, ethylene glycol, methanol and
      glycerol to loach (Misgurnus fossilis) sperm and the effect on subsequent embryo
      development.
AB  - The process of sperm cryopreservation consists of several steps: equilibration of
      sperm in cryoprotectant medium, freezing of sperm to subzero temperatures, low
      temperature storage and thawing of the sperm suspension. It has been shown that
      cryopreservation can cause some damage to the genetic material of cells although
      the mechanism and significance of these changes are still unknown. The aim of
      this work was to study the effect of cryoprotectant equilibration process on
      genetic damage of Loach (Misgurnus fossilis) sperm, using embryo survival as an
      indicator. Decrease in embryo survival after the 20th stage is generally believed
      to result from the failure in the genome function of embryos. In the first set of
      the experiments, Loach sperm were equilibrated in cryoprotectants Me2SO, ethylene
      glycol, methanol and glycerol (0.6, 1.2, 2.5 M) for 60 min at 10 degree C. The
      effect of cryoprotectant equilibration on sperm was evaluated based on the
      survival of embryos derived from cryoprotectant treated sperm. Embryo survival
      was evaluated at the following stages: 7th, 14th, 17th, 20th, 23rd, 26th, 31st,
      34th, 35th, 36th and 37th. Cryoprotectants at concentrations greater than 1.2 M
      had significant effect on the survival of the embryos after the 20th stage. The
      effect of glycerol was the most significant with 64.8 +/- 2.4% of embryos
      survival compared to 77.0 +/- 2.4% for control. Me2SO treatment also effects
      embryo survival significantly. Possible mechanisms of the genetic instability of
      cryoprotectants are discussed.

PMID- 14671689
TI  - GUS gene remains stable in transgenic citrus callus recovered from
      cryopreservation.
AB  - The conservation of transgenic materials is very important, paticularly for their
      potential future use in crop development. In this study, transgenic callus
      cultures of 'Newhall' navel orange (Citrus sinensis Osbeck) were cryopreserved by
      a vitrification method. Transgenic calluses survived cryopreservation and
      recovered under normal culture conditions. The results of PCR (Polymerase Chain
      Reaction) amplification, Southern blotting and SSCP (Single-Strand Conformation
      Polymorphism) assay showed that the GUS gene was still maintained in the genome
      of callus cultures recovered from cryopreservation. X-Gluc staining further
      indicated GUS gene expression in callus cultures recovered from cryopreservation.

PMID- 14671690
TI  - Importance of explant size and origin and of preconditioning treatments for
      cryopreservation of garlic shoot apices by vitrification.
AB  - This paper investigates the effect of the origin and size of the explants
      employed and of the preconditioning (cold acclimation, preculture) and loading
      treatments on survival and regeneration of cryopreserved garlic shoot apices
      using vitrification with the PVS3 vitrification solution. Both the origin and
      size of explants had a significant effect on regeneration of cryopreserved
      apices. Higher regeneration was generally observed with apices excised from bulbs
      and bulbils, followed by cloves, and those originated from larger propagules
      regrew more rapidly. Smaller apices (1.5 or 3.0 mm in diameter) displayed higher
      regeneration than large ones (4.5 mm in diameter). Cold acclimation at 5 degree C
      of apices before freezing had no positive effect on regeneration after
      cryopreservation. Preculture of apices at 10 or 23 degree C for more than 3 days
      had a detrimental effect on regeneration. The optimal sucrose concentration in
      the preculture medium was 0.3-0.5 M. Loading apices for 30 or 60 min at 23 degree
      C in medium containing 2 M glycerol + 0.4 M sucrose or 1 M glycerol + 0.8 M
      sucrose had no effect on regeneration after cryopreservation, in comparison with
      apices cryopreserved without loading treatment. Under optimal conditions,
      regeneration of cryopreserved apices sampled from large cloves was above 90
      percent.

PMID- 14671691
TI  - Cold storage and cryopreservation of hops (Humulus l.) shoot cultures through
      application of standard protocols.
AB  - The USDA-ARS National Clonal Germplasm Repository (NCGR) stores the global
      diversity of Humulus for the US Plant Germplasm System as trellised plants in a
      field genebank. In vitro storage and cryopreservation are now considered
      excellent ways to provide medium and long-term storage for plant collections.
      Developing a new cryopreservation or cold storage protocol for every accession or
      genus of large multi-crop collections can be a very time consuming and long-term
      activity. We propose that standard cold storage and cryopreservation techniques
      used for other temperate crop genera would be successful for additional crops
      with few modifications. This study was initiated to determine if a large
      collection of hops germplasm could be successfully stored with techniques
      developed for unrelated genera. In this study we characterized the response of
      diverse Humulus genotypes to in vitro storage under low light at 4 degree C
      following techniques used for strawberry and mint plants, and cryopreservation in
      liquid nitrogen by slow cooling with a pear protocol. The average storage time
      without transfer for the 70 genotypes evaluated was 14 +/- 3.5 months with a
      range of 6 to 26 months. Mean recovery of cryopreserved shoot tips of accessions
      with 1-wk cold acclimation was 41 +/- 18 percent and increased to 54 +/- 13
      percent with 2-wk cold acclimation. This demonstrates that application of a well
      tested standard technique can provide a quick start for storing additional
      germplasm collections.

PMID- 14671692
TI  - Adjuncts to improve patency of infrainguinal prosthetic bypass grafts.
AB  - The superiority of autologous venous conduit for infrainguinal arterial bypass
      has been well documented, especially when the bypass extends below the knee or to
      the tibial arteries. Nevertheless, when adequate autologous vein is not
      available, prosthetic bypasses (eg, polytetrafluoroethylene [PTFE] or Dacron) are
      often used in limb-salvage situations. The inferior long-term patency of these
      infrainguinal prosthetic bypasses has been documented by a number of studies. One
      such study reported a prospective multicenter randomized trial with only a 12%
      primary patency for infrapopliteal prosthetic bypasses after 4 years. Another
      study reported a similar experience with infragenicular bypasses with PTFE for
      limb salvage even for above-knee (27%, 5 year) and below-knee (25%, 5 year)
      femoral-popliteal bypasses. The reported PTFE graft patency was consistently
      inferior to that achieved with autologous vein for limb salvage. Dacron grafts
      appear to have similar patency rates to PTFE. In an attempt to improve prosthetic
      graft patency, a number of surgical and medical adjuncts have been developed. In
      this review, the authors discuss these adjuncts and their impact on infrainguinal
      prosthetic graft patency.

PMID- 14671693
TI  - Critical appraisal of cardiac risk stratification before elective vascular
      surgery.
AB  - This study was undertaken to evaluate the efficacy of the cardiac risk
      stratification protocol proposed by the American College of Cardiology/American
      Heart Association (ACC/AHA) in predicting cardiac morbidity and mortality
      associated with elective, major arterial surgery. Cardiac risk stratification
      using ACC/AHA guidelines was done on 425 consecutive patients before 481 elective
      cerebrovascular (n = 146), aortic/inflow (n = 166), or infrainguinal (n = 169)
      procedures at an academic Veterans Affairs Medical Center. Cardiac risk was
      stratified as low, intermediate, or high based on clinical risk factors, such as,
      Eagle criteria, history of cardiac intervention, patient functional status,
      results of noninvasive cardiac stress testing, and coronary angiography with
      coronary revascularization performed when appropriate. Outcomes (myocardial
      infarction, unstable angina, congestive heart failure, ventricular arrhythmia,
      cardiac death, and mortality) within 30 days of surgery were compared between the
      various risk stratification groups. Univariate and multivariate analyses were
      used to identify clinically useful prognostic variables from the preoperative
      cardiac evaluation algorithm. Overall mortality (1.7%), cardiac death (0.4%), and
      adverse cardiac event (4.8%) rates were low, but cardiac death and morbidity were
      increased (p < 0.05) in high-risk stratified patients (3.4%, 11.9%) compared to
      intermediate (0%, 2.8%) and low (0%, 4.0%) cardiac risk groups. The presence of 3
      vessel angiographic coronary artery occlusive disease was an independent
      predictor of cardiac morbidity, while inducible ischemia by cardiac stress
      imaging was not. Previous coronary revascularization was associated with
      increased mortality as was the development of a non-cardiac complication. Cardiac
      risk assessment identified 78 (18%) patients with indications for coronary
      angiography. Angiographic findings resulted in coronary artery intervention (9
      angioplasty; 4-bypass grafting) in 13 (3%) patients who experienced no adverse
      cardiac events after the planned vascular surgery (15 procedures). Cardiac risk
      stratification using ACC/AHA guidelines can predict adverse cardiac events
      associated with elective vascular surgery; however, protocol modification by
      increased reliance on Eagle criteria and less use of cardiac stress testing can
      improve identification of the "highest risk" patients who may benefit from
      prophylactic coronary intervention.

PMID- 14671694
TI  - Endovascular treatment of the thoracic aorta.
AB  - Open surgical repair has been considered the mainstay of therapy for thoracic
      aortic aneurysms, both elective and emergency procedures alike. Recent advances
      in endovascular technology have made endovascular stentgraft placement a
      therapeutic modality that is minimally invasive and potentially a safer treatment
      for aneurysmal disease of the descending thoracic aorta. Moreover, this
      technology may be appropriate for other diseases of the thoracic aorta, including
      traumatic disruptions and dissections. There appears to be an increase in the
      diagnosis, and therefore incidence, of these various thoracic aortic pathologies,
      owing both to improvement in imaging capabilities and longer life expectancies.
      In distinction to endovascular repair of infrarenal aortic aneurysms, the
      evolution of thoracic stentgrafts has progressed more slowly as there has yet to
      exist a clinically proven device after 10 years of clinical trials. However, the
      enthusiasm for this technology persists, for it may indeed hold the potential for
      the greatest patient benefit as conventional open surgical repair continues to
      offer serious morbidity and mortality rates. This paper reviews the current
      status of thoracic aortic stentgrafts, including recent clinical studies, device
      failures and refinements, and future directions.

PMID- 14671695
TI  - Cerebral oximetry monitoring during carotid endarterectomy: effect of carotid
      clamping and shunting.
AB  - Cerebral oximetry is a simple method of measuring regional cerebral oxygen
      saturation (rSO(2)). One promising application is its use during carotid
      endarterectomy (CEA) to help minimize the risk of perioperative stroke. The
      authors used the INVOS-4100 cerebral oximeter at several steps during CEA to
      measure the effect of carotid clamping and shunting on rSO(2). The authors
      prospectively evaluated 42 consecutive CEAs in 40 patients. All had CEA under
      general anesthesia with the routine use of a Javid shunt. The INVOS-4100 oximeter
      was used to measure rSO(2) before clamping (t1), after clamping but before
      shunting (t2), 5 minutes after shunt insertion (t3), and after patch closure with
      reestablished flow (t4). The Wilcoxon signed-rank and rank-sum tests were used
      for analysis. Clamping of the internal carotid artery (t1 vs t2) resulted in a
      drop of ipsilateral rSO(2) by -12.3% (p < 0.001). Shunt insertion (t2 vs t3)
      increased rSO(2) by 10.9% (p < 0.001). Contralateral rSO(2) for the same time
      periods was insignificant. Patients with preoperative neurologic symptoms had a
      greater decrease in rSO(2) after clamping (-18.4%) compared with a decrease of 
      10.4% in asymptomatic patients (p = 0.037). Cerebral oximetry monitoring is
      simple and inexpensive. The study showed statistically significant changes in
      rSO(2) as a result of clamping and shunting of the carotid artery. Symptomatic
      patients had a greater drop in rSO(2).

PMID- 14671696
TI  - Low-molecular-weight heparin versus saphenofemoral disconnection for the
      treatment of above-knee greater saphenous thrombophlebitis: a prospective study.
AB  - The objective of this study was to assess the efficacy, safety, and cost of low
      molecular-weight heparin compared to saphenofemoral disconnection for the
      treatment of internal saphenous proximal thrombophlebitis (SPT). Eighty-four
      consecutive patients diagnosed as presenting SPT alone (symptoms/echo-Doppler)
      were divided into 2 comparable groups treated with (1) saphenofemoral
      disconnection under local anesthesia with a short hospital stay (n = 45) or (2)
      prospective enoxaparin on an outpatient basis for 4 weeks (n = 39). Informed
      consent was obtained and inclusion, exclusion, and withdrawal criteria were
      established. Patients were followed up at 1, 3, and 6 months. Thirty patients per
      group completed the study requirements. In the disconnection group, 2 patients
      (6.7%) presented complications of the surgical wound, 1 (3.3%) had SPT recurrence
      (however, there was no deep venous thrombosis), and 2 (6.7%) had nonfatal
      pulmonary embolism confirmed by radionuclide scan. In the enoxaparin group, there
      were 2 cases (6.7%) of minor bleeding (epistaxis and rectal bleeding) and 3 (10%)
      recurrences of SPT. In the enoxaparin group there was no case of progression of
      the thrombosis to the deep venous system or pulmonary embolism. The study found
      no statistically significant differences between saphenofemoral disconnection and
      enoxaparin in the treatment of SPT, but the low-molecular-weight heparin group
      had socioeconomic advantages.

PMID- 14671697
TI  - Lesser saphenous vein thrombophlebitis: its natural history and implications for
      management.
AB  - Little attention has been given to superficial thrombophlebitis and particularly
      to lesser saphenous vein thrombophlebitis (LSVT) by vascular surgeons. A
      prospective nonrandomized study was conducted to assess LSVT's potential
      association with deep venous thrombosis (DVT) as well as its natural history.
      Between January 1994 and December 1995, the authors reviewed 33 cases of LSVT
      detected by duplex scanning in 32 patients at their institution's vascular
      laboratory. Combined LSVT/DVT was treated with heparin and warfarin. LSVT alone
      or LSVT plus greater saphenous vein thrombophlebitis (GSVT) were treated with
      local warm compresses and nonsteroidal antiinflammatory drugs. Follow-up scans
      were obtained in 23 of the 32 patients and ranged from 2 weeks to 18 months after
      diagnosis of LSVT. Thirty-one patients had unilateral LSVT and 1 patient had
      bilateral LSVT. Isolated LSVT was found in 9 patients (28%), LSVT combined with
      DVT occurred in 21 patients (65.6%), and 2 patients had LSVT/GSVT. LSVT was
      contiguous with DVT in 15 patients, and in 5 patients it was noncontiguous.
      Within 3 months, 9 of 16 patients (56%) with LSVT/DVT had complete or partial
      resolution of their LSVT, and 1 (14%) of the 7 patients with LSVT and LSVT/GSVT
      had improved. Within 18 months, 13 of 16 patients (81%) with LSVT/DVT had
      complete resolution of their thrombus while only 3 of 7 patients (43%) with LSVT
      and LSVT/GSVT had resolved. These data show that LSVT is more often associated
      with DVT (65.6%) than previously believed. While most LSVT will improve in 18
      months, those associated with DVT will resolve sooner. Whether anticoagulation
      accounted for this difference remains to be proven.

PMID- 14671698
TI  - Duplex imaging of the renal arteries with contrast enhancement.
AB  - Duplex ultrasound evaluation of the renal arteries is a technically challenging
      procedure. Its accuracy is significantly influenced by operator expertise and
      patient factors, such as overlying bowel gas and obesity. Intravenous microbubble
      contrast agents enhance vascular reflective acoustic signals and may improve
      ultrasound diagnostic accuracy. The clinical usefulness of such a contrast agent
      in the renal vasculature was examined prospectively. A total of 22 patients (16
      males and 6 females) with mean age of 63 +/-3 years with suspected abdominal
      vascular disease were studied prospectively. A complete color flow duplex imaging
      study of the renal vasculature was performed. This was then followed by an
      identical examination during which an ultrasound contrast agent (Definity, DuPont
      Pharmaceutical) was infused intravenously at a rate of 2 to 4 mL/min. In addition
      to imaging of the vessels, the peak systolic velocity and Doppler waveforms of
      the aorta and renal arteries were examined. These results were independently
      compared to results with contrast angiography. A mean of 67 mL of contrast was
      used per patient. Of the total of 43 renal arteries examined, the accuracy for
      the detection of occlusions was 75% (3 of 4) for both standard and contrast
      enhanced duplex ultrasound. The accuracy for the detection of hemodynamically
      significant stenosis was 50% (6 of 12) for standard and 75% (9 of 12) for
      contrast-enhanced duplex ultrasound. Visualization of normal or minimally
      diseased arteries was 94% (30 of 32) for standard and 97% (31 of 32) for contrast
      enhanced ultrasound. Although overall accuracy was not enhanced by the infusion
      of ultrasound contrast, 5 of 7 arteries not visualized by color flow duplex were
      detected following the infusion of contrast agent, resulting in an additional 10%
      (5 of 48) of vessels visualized. Peak systolic velocities were increased by an
      average of 10% in normal or minimally diseased vessels and 12% in stenotic
      vessels following contrast administration but these differences were not
      statistically significant. Contrast-enhanced duplex imaging of the renal arteries
      is safe but not routinely required when performed by an experienced sonographer.
      However, it may increase visualization and accuracy in patients with stenoses or
      when the vessels are not initially visualized. Although increased velocities are
      seen when contrast agent is used, this does not appear to necessitate different
      Doppler criteria at this time.

PMID- 14671699
TI  - Treatment of a late-appearing proximal type-1 endoleak after Ancure graft with an
      AneuRx cuff--a case report.
AB  - The authors describe the case of a patient who developed a type-1 proximal
      endoleak 10 months after Ancure stent graft placement, despite the lack of stent
      migration or measurable neck dilatation. The patient had been under observation
      for a persistent type-2 endoleak and was noted to have an increase in his
      aneurysm size. The use of an uncovered stent was unsuccessful, and he required a
      covered proximal extension cuff. This led to a resolution of the endoleak.
      Implications in terms of surveillance and possible etiologies are discussed.

PMID- 14671700
TI  - Allograft replacement of common iliac artery mycotic aneurysm caused by
      Bacteroides fragilis vertebral spondylitis--a case report.
AB  - Mycotic aneurysm secondary to vertebral spondylitis is a rare but life
      threatening pathology with high mortality and morbidity. The authors describe a
      successfully treated case of mycotic aneurysm of the common iliac artery
      complicated with vertebral spondylitis in a 74-year-old man. Under midline
      laparotomy, complete debridement of the infected tissues, in-situ replacement of
      the common iliac artery with cryopreserved aortic allograft, and iliac bone
      autotransplantation and omentopexy to fill the debrided cavity were performed.
      The postoperative course was uneventful, and he remains well 3 years after his
      operation without persistent infection or allograft rejection.

PMID- 14671702
TI  - Alternatives to animal testing: research, trends, validation, regulatory
      acceptance.
AB  - Current trends and issues in the development of alternatives to the use of
      animals in biomedical experimentation are discussed in this position paper. Eight
      topics are considered and include refinement of acute toxicity assays; eye
      corrosion/irritation alternatives; skin corrosion/irritation alternatives;
      contact sensitization alternatives; developmental/reproductive testing
      alternatives; genetic engineering (transgenic) assays; toxicogenomics; and
      validation of alternative methods. The discussion of refinement of acute toxicity
      assays is focused primarily on developments with regard to reduction of the
      number of animals used in the LD(50) assay. However, the substitution of humane
      endpoints such as clinical signs of toxicity for lethality in these assays is
      also evaluated. Alternative assays for eye corrosion/irritation as well as those
      for skin corrosion/irritation are described with particular attention paid to the
      outcomes, both successful and unsuccessful, of several validation efforts.
      Alternative assays for contact sensitization and developmental/reproductive
      toxicity are presented as examples of methods designed for the examination of
      interactions between toxins and somewhat more complex physiological systems.
      Moreover, genetic engineering and toxicogenomics are discussed with an eye toward
      the future of biological experimentation in general. The implications of gene
      manipulation for research animals, specifically, are also examined. Finally,
      validation methods are investigated as to their effectiveness, or lack thereof,
      and suggestions for their standardization and improvement, as well as
      implementation are reviewed.

PMID- 14671701
TI  - Surgical correction of pseudoaneurysm of the extracranial carotid artery: the
      usefulness of retrograde cerebral perfusion--a case report.
AB  - Although a pseudoaneurysm of the common carotid artery is not encountered
      frequently, its surgical treatment is technically challenging. A case is reported
      of a large pseudoaneurysm of the right common carotid artery in a 45-year-old
      woman, presenting with respiratory distress, following a wound infection 3 months
      after tracheoplasty. Instead of a vascular shunt, deep hypothermic circulatory
      arrest with retrograde cerebral perfusion was used for protection of the brain
      against hypoxia during the arterial reconstruction. The pseudoaneurysm was easily
      corrected with an autologous saphenous vein, without any hazardous dissection
      through the dense fibrosis around the fragile pseudoaneurysm, under circulatory
      arrest.

PMID- 14671703
TI  - The 3Rs and animal welfare - conflict or the way forward?
AB  - The animal experiment is central to the 3R concept. In European law, animal
      experiments are classed according to their aims. In the German animal protection
      law, they are classed, e.g. as interventions and treatments for experimental
      purposes, for further education and training, or for the production, preparation,
      storage or multiplication of substances, products or organisms and for the
      fulfillment of legal requirements, and are thus regulated with varying
      strictness. In contrast, in Switzerland all such measures performed on live
      animals underlie the same approval requirements. For animal welfarists, the term
      "animal experiment" includes every intervention and every treatment which is
      associated with pain, fear and/or suffering and does not directly benefit the
      respective animal. In the animal experiment, the animal concerned usually suffers
      as a human would, independent of the experimental goal. Expecting an animal to
      suffer a treatment one would not want to undergo oneself cannot be in accord with
      an ethic of respect for fellow creatures. Animal welfarists aim to save animals
      such suffering. Consequently, they demand the immediate abolition of all animal
      experiments. From the perspective of those who allow animal experiments to be
      performed or who perform them themselves, the goal of the experiment is more
      important than the animal. Therefore, the following question is central to 3R
      research: "Can I reach my goal while causing the animal less suffering, using
      fewer animals or without using animals at all?" The starting point is that the
      ethical responsibility for man is valued higher than that for the animal. The aim
      is to protect humans from harm caused by substances and products or from unwanted
      side effects of medication, to understand diseases and to search for a cure or
      alleviation of these. When a scientist reaches his goals without using animals,
      the demand of animal welfarists to abolish the animal experiment is fulfilled.
      These aspects do of course not encompass all the differences and agreements in
      the positions of animal welfarists and those who support animal experiments. It
      is not without reason that the discussion around animal experiments is
      multifaceted and continues to be held intensely from all positions. The classic
      pattern of a discussion entails that the one side collects the arguments which
      illustrate that animal experiments lead to wrong results, cannot be transferred
      and finally stand more against than for the good of mankind. The latter statement
      is valid, because the wrong methods benefit from investment, thus preventing or
      hindering new, better research and application of knowledge. The other side uses,
      among others, the argument that the person performing the experiment knows the
      limits of the test procedure and can deal with them accordingly. For further
      defense of current and future animal experiments, scientists like to present
      their organ transplant patients, i.e. those who can only lead a life worth living
      thanks to continuous medication, and admonish that patients with Alzheimer's or
      Parkinson's disease or with cancer put their last hope into new medical insights
      which can only be gained with animal experiments. Animal welfarists argue against
      this, that the motivation for animal experiments does not always lie in the
      ethical responsibility for mankind, but also in pure gain of knowledge, titles
      and money. After all, they also claim that they are protecting man, animal and
      environment from diseases and want to help them. It is not about saving animals
      at any price, even including human life, as is commonly brought against them. But
      they are also not prepared to accept that without real necessity or at any hint
      of a dilemma, the decision always falls immediately against the animal. The
      animal experiment may no longer be the method of choice, both for ethical and
      also for scientific reasons. What does all of this have to do with 3R research?
      It is a fact that animal experiments are still the method of choice, the "gold
      standard". The official German statistics on animal experiments in 2001
      (Governmental animal protection report, 2002) counts a total of 2.13 mill.
      experimental animals, with a tendency towards a further increase. The increase is
      ascribed to animal experiments especially in basic research, counting 926,294
      animals. The other more than a million animals were used for research and
      development of products and equipment for human, dental or veterinary medicine
      (509,101), the production or quality control of products or equipment for human,
      dental or veterinary medicine (289,273), toxicological investigations or other
      safety tests (189,996), the diagnosis of diseases (26,508), education and
      training (39,625) and other purposes (145,764). Before this background, all
      activities which lead away from animal experiments or reduce the suffering caused
      in the remaining experimental animals must be judged as positive developments. 3R
      research leads to a reduction of animal experiments and animal suffering. At the
      same time, the earnest consideration of the 3Rs also leads to a critical and
      specific discussion of the animal experiment in question.

PMID- 14671704
TI  - [Man and his fellow-creatures under ethical aspects].
AB  - It may not be spectacular, but the compilation of a new comment on the German
      Animal Protection Law before the background of the new constitution is the most
      important medium and long-term event since the inclusion of animal protection
      into the constitution in Germany. The comment was also occasion to mark the
      ethically motivated change in the awareness of society, which has strengthened
      continuously since the eighties, not only entering the law as the "responsibility
      of mankind for animals as fellow creatures" but also posing a question to the
      ethicists, who have since been searching for answers. Eisenhart von Loeper who
      wrote the "Introduction to the law on the relationship between man and animal"
      and the comment on the first principle paragraph followed these endeavours of
      theology and philosophy. Under point 6.3 of this report on the literature some
      important results are summarised under the keywords "species-spanning humanity",
      "fellow creaturism", "anthropocentrism-criticism", "principle of equality" and
      "equity and rights of animals". Significant differences are evident in the
      comparison of the different concepts that have been developed in animal ethics,
      also regarding the expanse of the demands made for the benefit of the animals.
      The general opinion in philosophy that animal ethics and animal protection can
      only apply to the higher developed animals points towards a tendency to consider
      only a kind of "animal elite" morally relevant and worthy of protection and to
      exclude the mass of others as soulless automats by keeping the status quo and
      exposing them to indiscriminate use by humans. Species-spanning equality must be
      decidedly demanded.

PMID- 14671705
TI  - [Xenotransplantation from a Christian-ethical perspective].
AB  - Xenotransplantation is a question of "ethics between man and animal". Because
      those affected in different ways by xenotransplantation (patients, relatives,
      medical doctors, laypeople) have different perceptions, "foreign" perspectives
      must be consciously considered next to one's own perspective in the ethical
      judgement. As xenotransplantation is still at the stage of preclinical research,
      this special opportunity for an early public ethical discussion should be taken.
      According to biblical teaching, man is responsible for his fellows before God,
      therefore every decision of a patient (or a doctor) in favour of a
      xenotransplantation made without consideration of the social environment or the
      society as a whole cannot be ethically justified. From the Jewish-Christian point
      of view, the "innate value of man's fellow creatures" should be considered. What
      happens to the animals used for research into transplantation may not simply
      "vanish" before the vision of a successful xenotransplantation. What man's
      responsibility to creatures should prevent commonly happens: animals are
      exploited as instruments or treated as objects to reach human goals, they are
      perceived only as their utility value. We humans, with God's biblical mandate for
      our fellow creatures, must remember that the unavoidable weighing up between the
      (proposed) welfare of man and the welfare of animals should not be decided to the
      detriment of the animals too easily. The effects of medical technological
      possibilities on the conception of man and on our value system show themselves in
      a special way in xenotransplantation. Are the hopes set in xenotransplantation an
      expression of a mechanistic understanding of the human body and a conception of
      man that blends out the mortality and imperfection of human life? Focussing on
      human-ethical aspects leads to the neglect of the animal-ethical aspects by some
      Protestant ethicists. However, it is necessary to forego at least extremely
      severe animal experiments and so also to do without the possible gain of
      knowledge, i.e. to consciously limit research interests for ethical reasons. The
      tendency towards the reduction of animal experiments should not be reverted by
      research into xenotransplantation. The ethical evaluation of xenotransplantation
      should also consider whether economic interests are placed above the welfare of
      humans and animals, thus supporting questionable research processes. Justice and
      partisanship for the disadvantaged is a central aspect of biblical tradition. The
      problem in deciding what is fair in xenotransplantation is multifaceted: How can
      fair allocation of organs be ensured when both animal and human organs are
      available at the same time? What effects will this medical technology have on the
      distribution of the (limited) resources on the national health system? And
      finally: can such a cost-intensive technology helping only a few be justified in
      the light of the lack of basic medical care in the poor regions of the earth? A
      technology which many experts warn will result in the opposite of the original
      goal, i.e. reduction of the lack of organs.

PMID- 14671706
TI  - [Question the animal experiment in a new way].
AB  - When asking what the subject of an animal experiment is, you are inclined to
      answer that the animal is the subject of the animal experiment. However in
      answering this, you need to analyse the term "animal". This paper attempts to
      define the term "animal" by using the impression of "body" (German: "Leib").
      Starting from the human body the paper shows the body's perceptive ability which
      entails self-perception in the sense of self-awareness as well as perception of
      the surroundings. Animals, which are also bodily beings, are like humans capable
      of self-perception in the sense of self-awareness. So the term "body" makes a
      connection between humans and animals. In the result of this it becomes clear
      that, of course, animals are the subject of animal experiments as are humans.

PMID- 14671707
TI  - Alternatives to the use of fetal bovine serum: serum-free cell culture.
AB  - Serum is commonly used as a supplement to cell culture media. It provides a broad
      spectrum of macromolecules, carrier proteins for lipoid substances and trace
      elements, attachment and spreading factors, low molecular weight nutrients, and
      hormones and growth factors. The most widely used animal serum supplement is
      fetal bovine serum, FBS. Since serum in general is an ill-defined component in
      cell culture media, a number of chemically defined serum-free media formulations
      have been developed in the last two decades. Besides modern cell biological
      advances in cell and tissue culture and efforts towards a standardisation of cell
      culture protocols in Good Cell Culture Practice, in addition, considerable
      ethical concerns were raised recently about the harvest and collection of fetal
      bovine serum. Thus, in order to decrease the annual need for bovine fetuses in
      terms of the 3Rs through any reduction in the use or partial replacement of
      serum, as well as in terms of an improvement of cell and tissue culture
      methodology, serum-free cell culture represents a modern, valuable and
      scientifically well accepted alternative to the use of FBS in cell and tissue
      culture.

PMID- 14671708
TI  - A reexamination of the mechanisms underlying the arteriovenous chloride shift.
AB  - The chloride shift is the movement of Cl(-) from the plasma into erythrocytes as
      blood moves from the arterial to the venous end of systemic capillaries. The
      traditional explanation for the chloride shift emphasizes the causative roles of
      the rise in Pco(2) and the exclusive presence of carbonic anhydrase within the
      red blood cell. The purpose of this article is, first, to reexamine two aspects
      of the chloride shift that we feel are traditionally underemphasized. They are
      the role of hemoglobin in causing the chloride shift and the affect of the
      chloride shift on the acid-base status of the blood. Second, we wish to reconcile
      more recent work with the traditional understanding of the chloride shift. The
      chloride shift has never been modeled from the perspective of the Stewart strong
      ion approach. Similarly, the traditional understanding has generally treated Cl(
      ) as a passive participant in the chloride shift whose role was simply to replace
      the lost negative charge of the outward moving HCO-3. More recent work has
      suggested that the ingoing Cl(-) is important for both O(2) unloading and acid
      base balance of the blood. We conclude this article with a model of the chloride
      shift that uses the Stewart approach and, though harmonious with the traditional
      understanding, highlights the importance of hemoglobin and Cl(-) in the chloride
      shift.

PMID- 14671709
TI  - Dropping like flies: environmentally induced impairment and protection of
      locomotor performance in adult Drosophila melanogaster.
AB  - In Drosophila, heat shock (HS) during the pupal stage chronically hinders adult
      locomotor performance by disrupting wing development and cellular and/or tissue
      level mechanisms that support walking and flight. Furthermore, heat pretreatment
      (PT) protects locomotor function against these disruptions. HS flies with
      abnormal wings were less able to alter trajectory in free fall relative to
      control, PT-only, and PT+HS wild-type flies. This deficit was less severe but
      still present in HS-only flies with wild-type wings. Transgenic increases in the
      copies of genes encoding the major inducible heat-shock protein of Drosophila
      melanogaster, Hsp70, also protected walking ability from disruption due to pupal
      HS. Walking velocity did not differ between excision (five natural hsp70 copies)
      and extra-copy (five natural and six transgenic hsp70 copies) flies in the
      control, PT, and PT+HS groups, nor did velocity vary among these thermal
      treatment groups. HS dramatically reduced walking velocity, however, but this
      effect occurred primarily in the excision flies. These results suggest that Hsp70
      and other mechanisms protect against heat-induced locomotor impairment.

PMID- 14671710
TI  - High-energy phosphate metabolism during exercise and recovery in temperate and
      Antarctic scallops: an in vivo 31P-NMR study.
AB  - In vivo (31)P-nuclear magnetic resonance (NMR) spectroscopy was used to measure
      the levels of ATP, phospho-l-arginine (PLA), and inorganic phosphate in the
      adductor muscle of the Antarctic scallop Adamussium colbecki and two temperate
      species, Aequipecten opercularis and Pecten maximus. Graded exercise regimes from
      light (one to two contractions) to exhausting (failing to respond to further
      stimulation) were imposed on animals of each species at its habitat temperature
      (0 degrees vs. 12 degrees C, respectively). NMR spectroscopy allowed noninvasive
      measurement of metabolite levels and intracellular pH at high time resolution (30
      120-s intervals) during exercise and throughout the recovery period. Significant
      differences were shown between the magnitude and form of the metabolic response
      with increasing levels of exercise in each species. After exhaustion, short-term
      (first 15 min) muscle alkalosis was followed by acidosis of up to 0.2 pH units
      during the recovery process. Aequipecten opercularis had similar resting muscle
      PLA levels compared with either P. maximus or A. colbecki but used a fivefold
      greater proportion of this store per contraction and was able to perform only
      half as many claps (maximum of 24) as the other species before exhaustion. All
      species regenerated their PLA store at a similar rate despite different
      environmental temperatures. These findings argue for some cold compensation of
      muscular performance and recovery capacities in the Antarctic scallop, albeit at
      levels of performance similar to scallops with low activity lifestyles from
      temperate latitudes.

PMID- 14671711
TI  - Water-balance characteristics respond to changes in body size in subantarctic
      weevils.
AB  - Several environmental factors leading to size-dependent mortality influence
      insect body size. Few investigations have been concerned with the ways in which
      the mechanisms underlying variation in water-balance characteristics evolve in
      response to changes in body size that occur independently of water-balance
      requirements. Using an explicitly phylogenetic analysis, we show how body size
      has changed over time in the Ectemnorhinus group of weevils and how water-balance
      characteristics have evolved in response to this change and changes in habitat
      use. The basal species in the group are all large bodied and from moist
      environments. In response to a change in resource availability, there was a
      marked decline in size within the group. Despite the reduction in water content
      and dehydration tolerance that this meant, evolution of low whole-animal water
      loss rates and high tolerance of dehydration resulted in conservation of
      desiccation resistance. The return to moist habitats in the group resulted in a
      reduction in dehydration tolerance and an increase in water-loss rate. Thus,
      dehydration tolerance and water-loss rate respond rapidly both when there is
      selection for water conservation and when this requirement is relaxed. Future
      laboratory selection experiments might usefully explore both directions of water
      balance evolution.

PMID- 14671712
TI  - Environmental hypoxia does not constrain the diurnal depth distribution of free
      swimming Nautilus pompilius.
AB  - The behaviour of Nautilus pompilius swimming freely in a controlled mesocosm
      (tower tank, 4 m diameter x 10.5 m deep) was monitored using ultrasonic depth
      telemetry. Initially depths were monitored in water equilibrated with air. Then
      the bottom 3.5 m were rendered hypoxic (Po(2) <20 mmHg) and depths monitored
      again. A thermocline at 7-m depth (17 degrees C below, 20 degrees C above)
      prevented mixing with the top, normoxic water. Mean depth was significantly
      greater during the light phase (8.9 m) of the 12L : 12D photoperiod than the dark
      phase (5.6 m), but this was not affected by hypoxia. During the light phase
      animals preferred the bottom 2.5 m of the tank but showed no specific preference
      for any depth range during the dark phase. Hypoxia did not alter these patterns
      of depth preference, though one animal made regular excursions toward normoxic
      water during the light phase. Vertical swimming activity was almost twofold
      greater during the dark phase and was not affected by hypoxia. These data suggest
      that, at least over the short term, Nautilus are not constrained from entering
      areas with low dissolved oxygen. This hypoxia tolerance may be attributed to the
      large onboard oxygen stores and suppressed metabolism during hypoxia.

PMID- 14671713
TI  - The effects of an acute temperature change on the metabolic recovery from
      exhaustive exercise in luvenile Atlantic salmon (Salmo salar).
AB  - This research examined the influence of acute changes of water temperature on the
      recovery processes following exhaustive exercise in juvenile Atlantic salmon
      (Salmo salar). White muscle phosphocreatine (PCr), ATP, lactate, glycogen,
      glucose, pyruvate, plasma lactate, and plasma osmolality were measured during
      rest and at 0, 1, 2, and 4 h following exhaustive exercise in fish acclimated and
      exercised at 12 degrees C and acutely exposed to either 6 degrees C or 18 degrees
      C water during recovery. An acute exposure to 6 degrees C water during the
      recovery period resulted in a severe reduction of metabolic recovery in salmon.
      However, metabolites such as muscle PCr and ATP and plasma lactate recovered very
      quickly (2-4 h) in fish acutely exposed to 18 degrees C during recovery. Overall,
      differences exist when postexercise metabolite levels are compared between
      acclimated fish and those fish acutely exposed to different water temperatures
      (either higher or lower). Taken together, the findings of the acute experiments
      suggest that at some point following exercise fish may seek warmer environments
      to speed the recovery process. However, the relationship between behavioural
      thermoregulation and recovery following exhaustive exercise in fish is not well
      understood.

PMID- 14671714
TI  - Intracerebroventricular injections of noradrenaline affect brain energy
      metabolism of rainbow trout.
AB  - To assess the role of noradrenaline (NA) as a possible regulator of brain energy
      metabolism in teleost fish, the impact of increased noradrenaline levels within
      the brain on several parameters of energy metabolism was assessed in rainbow
      trout brain. Accordingly, two different doses of noradrenaline, producing
      increases in brain NA levels comparable to those occurring in several
      physiological processes in nature, were selected. In a subsequent set of three
      different experiments, fish were intracerebroventricularly injected with 1 microL
      100 g(-1) body weight of Cortland saline alone (control) or containing NA (5 nmol
      NA and 10 nmol NA); after 30 min, brain and plasma samples were taken to assess
      changes in parameters of energy metabolism due to NA treatment. The results
      obtained clearly show dose-dependent changes in NA-treated fish in several
      parameters, including decreased glycogen and ATP levels, increased lactate and
      pyruvate levels, decreased fructose 1,6-bisphosphatase activity, and increased
      pyruvate kinase and lactate dehydrogenase activities. Altogether, the present
      experiments show for the first time in a teleost fish evidence supporting that
      increased noradrenaline levels in the brain elicit metabolic changes in the brain
      (enhanced glycogenolysis and glycolysis), resulting in an increased energy
      demand. These metabolic changes may be related to those occurring under several
      physiological conditions in nature such as hypoxia, in which increased energy
      demand and increased noradrenaline levels occur in the brain simultaneously.

PMID- 14671715
TI  - Clutch effects explain heart rate variation in embryonic frogs (Cave Coqui,
      Eleutherodactylus cooki).
AB  - Few physiological studies to date have focused on whether variation among sibling
      groups during development can account for often large, intraspecific
      physiological variation. In this study, we measured heart rate in the direct
      developing frog Eleutherodactylus cooki throughout its embryonic development and
      examined heart rate variation among egg clutches comprising from 10 to 40 eggs.
      Clutches were collected in the wild in Yubucoa, Puerto Rico, and individual eggs
      were maintained under equivalent conditions in the lab. Heart rate showed large
      increases during development, rising from about 40 beats min(-1) in the earliest
      stages to about 110 beats min(-1) at hatching. The effect of stage (averaged
      across clutches) was highly significant (P<0.001). However, repeated-measures
      MANOVA also revealed that there were highly significant effects on heart rate
      associated with both clutch (variation among clutches averaged across
      development; P<0.001) and clutch-stage interactions (differences among clutches
      in the developmental change in heart rate; P<0.0001). These effects and
      interactions reveal that throughout development, heart rate in siblings is much
      more similar than in nonsiblings and that sib groups follow different heart rate
      trajectories during their development. Collectively, these data indicate that
      "clutch effects" caused by genetic and/or maternal influences can strongly affect
      patterns of heart function during development within cave coqui populations. This
      phenomenon also occurs in bird eggs and armadillo neonates, suggesting that
      physiological variation attributable to clutch effects might be a widespread
      phenomenon in vertebrates.

PMID- 14671716
TI  - Cardiac output and shunt during voluntary activity at different temperatures in
      the turtle, Trachemys scripta.
AB  - Red-eared slider turtles (Trachemys scripta) were chronically instrumented with
      blood flow probes for a long-term study of voluntary behavior in an enriched
      laboratory setting. Cardiovascular measures consisting of total cardiac output
      (Q(tot)), pulmonary blood flow (Q(pul)), systemic blood flow (Q(sys)), net
      cardiac shunt (Q(shunt)), heart rate (HR), and stroke volume (SV) were obtained
      during spontaneous activity at a constant body temperature (Tb=2 degrees C) and
      at unstable (variable) T(b)'s ranging from 19 degrees to 37 degrees C. The
      effects of temperature and activity differed between the pulmonary and systemic
      circuits, with increases in Q(sys) due to HR alone, while both HR and SV
      contributed to gains in Q(pul). At stable 20 degrees C, cardiovascular responses
      during diving, submerged swimming, and walking were qualitatively similar, and
      increases in Q(tot) during activity ( approximately 2 x resting levels) were due
      to greater gains in Q(pul) than Q(sys). At unstable T(b)'s and in general, net
      Q(shunt) while active depended on the integration of individual physiological
      influences such as heating, cooling, and initial behavioral state acting on the
      cardiovascular system. During activity, net left-to-right (L-R) shunts
      predominated at constant T(b) of 20 degrees C (mean shunt fraction approximately
      30%-40%), while both net L-R and right-to-left (R-L) shunts of varying size were
      found at unstable T(b)'s (19 degrees - 37 degrees C).

PMID- 14671717
TI  - Measurement of maximum oxygen consumption in Guinea fowl Numida meleagris
      indicates that birds and mammals display a similar diversity of aerobic scopes
      during running.
AB  - Judgement of exercise performance in birds has been hampered by a paucity of data
      on maximal aerobic capacity. We measured the maximal rate of oxygen consumption
      (Vo2,max) in running guinea fowl Numida meleagris, a bird that has been used in
      several previous studies of avian running. Mean Vo2,max during level treadmill
      running was 97.5+/-3.7 mL O(2) kg(-1) min(-1) (mean+/-SEM, N=5). Vo2,max was on
      average 6% higher when the birds ran uphill compared with the value during level
      running (paired t-test, P=0.041, N=5). The mean basal rate of oxygen consumption
      (Vo2,bmr) of the same individuals was 7.9+/-0.5 mL O(2) kg(-1) min(-1). Mean
      factorial aerobic scope based on individually measured values of Vo2,max and
      Vo2,bmr was 13.2+/-0.6 (mean+/-SEM, N=5). This value was considerably lower than
      the factorial aerobic scope previously measured during running in Rhea americana,
      a large flightless ratite. The difference in factorial scope between these two
      running birds likely reflects the effects of body size as well as size
      independent differences in the ability to deliver and use oxygen. These data
      confirm a previous prediction that birds have a diversity of factorial aerobic
      scopes similar to that exhibited by mammals.

PMID- 14671718
TI  - Nonbreeding eastern curlews Numenius madagascariensis do not increase the rate of
      intake or digestive efficiency before long-distance migration because of an
      apparent digestive constraint.
AB  - The possibility of premigratory modulation in gastric digestive performance was
      investigated in a long-distance migrant, the eastern curlew (Numenius
      madagascariensis), in eastern Australia. The rate of intake in the curlews was
      limited by the rate of digestion but not by food availability. It was
      hypothesized that before migration, eastern curlews would meet the increased
      energy demand by increasing energy consumption. It was predicted that (1) an
      increase in the rate of intake and the corresponding rate of gastric throughput
      would occur or (2) the gastric digestive efficiency would increase between the
      mid-nonbreeding and premigratory periods. Neither crude intake rate (the rate of
      intake calculated including inactive pauses; 0.22 g DM [grams dry mass] or 3.09
      kJ min(-1)) nor the rate of gastric throughput (0.15 g DM or 2.85 kJ min(-1))
      changed over time. Gastric digestive efficiency did not improve between the
      periods (91%) nor did the estimated overall energy assimilation efficiency (63%
      and 58%, respectively). It was concluded that the crustacean-dominated diet of
      the birds is processed at its highest rate and efficiency throughout a season. It
      appears that without a qualitative shift in diet, no increase in intake rate is
      possible. Accepting these findings at their face value poses the question of how
      and over what time period the eastern curlews store the nutrients necessary for
      the ensuing long, northward nonstop flight.

PMID- 14671719
TI  - Plasticity in body composition in breeding birds: what drives the metabolic costs
      of egg production?
AB  - Body composition in vertebrates is known to show phenotypic plasticity, and
      changes in organ masses are usually rapid and reversible. One of the most rapid
      and reversible changes is the transformation of the female avian reproductive
      organs before breeding. This provides an excellent system to investigate the
      effects of plasticity in organ size on basal metabolic rate (BMR) through
      relationships between organ masses and BMR. We compared body composition of
      female European starlings (Sturnus vulgaris) during various reproductive stages
      over 3 yr and investigated the pattern of changes in reproductive and
      nonreproductive organ mass during follicular development and ovulation.
      Furthermore, we analyzed the relationship between organ mass and resting
      metabolic rate (RMR) in nonbreeding, laying, and chick-rearing females. Our
      analysis revealed marked variation in organ masses between breeding stages but no
      consistent pattern among years except for kidney and pectoralis muscle.
      Furthermore, changes in nonreproductive organs did not parallel the cycle of
      growth and regression of the reproductive organs. The oviduct gained 62% of its
      22-fold increase in mass in only 3 d, and oviduct regression was just as rapid
      and began even before the final egg of the clutch was laid, with 42% of the
      oviduct mass lost before laying of the final egg. In laying females, 18% of
      variation in mass-corrected RMR was explained by the mass of the oviduct
      (r2=0.18, n=80, P<0.0005), while pectoralis muscle mass in nonbreeding
      individuals and liver and gizzard mass in chick-rearing females were the only
      organs significantly related to RMR (r2=0.31-0.44). We suggest that the
      nonreproductive organs are affected more by changes in local ecological
      conditions than the reproductive state itself and that the activity and
      maintenance cost of the oviduct is high enough that selection has led to a very
      tight size-function relationship for this organ.

PMID- 14671720
TI  - Are hummingbirds facultatively ammonotelic? Nitrogen excretion and requirements
      as a function of body size.
AB  - Most birds are uricotelic. An exception to this rule may be nectar-feeding birds,
      which excrete significant amounts of ammonia under certain conditions. Although
      ammonia is toxic, because it is highly water soluble its excretion may be
      facilitated in animals that ingest and excrete large amounts of water. Bird
      pollinated plants secrete carbohydrate- and water-rich floral nectars that
      contain exceedingly little protein. Thus, nectar-feeding birds are faced with the
      dual challenge of meeting nitrogen requirements while disposing of large amounts
      of water. The peculiar diet of nectar-feeding birds suggests two hypotheses: (1)
      these birds must have low protein requirements, and (2) when they ingest large
      quantities of water their primary nitrogen excretion product may be ammonia. To
      test these hypotheses, we measured maintenance nitrogen requirements (MNR) and
      total endogenous nitrogen losses (TENL) in three hummingbird species (Archilochus
      alexandri, Eugenes fulgens, and Lampornis clemenciae) fed on diets with varying
      sugar, protein, and water content. We also quantified the form in which the by
      products of nitrogen metabolism were excreted. The MNR and TENL of the
      hummingbirds examined were exceptionally low. However, no birds excreted more
      than 50% of nitrogen as ammonia or more nitrogen as ammonia than urates.
      Furthermore, ammonia excretion was not influenced by either water or protein
      intake. The smallest species (A. alexandri) excreted a significantly greater
      proportion (>25%) of their nitrogenous wastes as ammonia than the larger
      hummingbirds ( approximately 4%). Our results support the hypothesis that nectar
      feeding birds have low protein requirements but cast doubt on the notion that
      they are facultatively ammonotelic. Our data also hint at a possible size
      dependent dichotomy in hummingbirds, with higher ammonia excretion in smaller
      species. Differences in proportionate water loads and/or postrenal modification
      of urine may explain this dichotomy.

PMID- 14671721
TI  - Immune response, not immune maintenance, is energetically costly in wild white
      footed mice (Peromyscus leucopus).
AB  - Understanding the cost of immune function is essential for more accurate
      characterization of energy budgets of animals and better understanding of the
      role of immunity in the evolution of life-history strategies. We examined the
      energetic cost of maintaining a normally functioning immune system and mounting a
      mild immune response in wild male white-footed mice (Peromyscus leucopus). To
      evaluate the cost of maintaining immunocompetence, we compared resting and daily
      metabolic rates (RMR; DMR) and masses of body organs of mice whose immune systems
      were suppressed by cyclophosphamide with those of control mice. To evaluate the
      cost of mounting an immune response, we measured RMR, DMR, and organ masses in
      mice whose humoral and cell-mediated immune responses had been stimulated by
      injections of sheep red blood cells and phytohemagglutinin, respectively.
      Immunosuppression resulted in a significant reduction in circulating leukocytes,
      by 225%, but no significant effect on metabolic rates or organ masses.
      Immunochallenged animals showed no significant differences in metabolic rates
      compared with control animals but did exhibit significantly smaller dry masses of
      the small intestine and testes, by 74% and 22%, respectively. We concluded that
      the cost of maintaining the immune system was minimal. In contrast, there was a
      significant energetic cost of mounting an immune response that, depending on its
      magnitude, can be met through reductions in energy allocation to other
      physiological systems.

PMID- 14671722
TI  - Repeated restraint and sampling results in reduced corticosterone levels in
      developing and adult captive American kestrels (Falco sparverius).

PMID- 14671723
TI  - Tissue damage precludes the use of the everted sleeve technique to measure
      nutrient uptake in a small migratory shorebird, the western sandpiper (Calidris
      mauri).

PMID- 14671724
TI  - Prostaglandins: then and now and next.

PMID- 14671725
TI  - Maternal autoantibodies and congenital heart block: mediators, markers, and
      therapeutic approach.

PMID- 14671726
TI  - Cyclooxygenase-2 and prostaglandins in articular tissues.
AB  - OBJECTIVES: To provide an overview on: 1) the expression of cyclooxygenase (COX)
      2 in articular tissues; 2) the role of prostaglandin E2 (PGE2) in these tissue
      functions; and 3) clinical trials with COX-2-selective nonsteroidal anti
      inflammatory drugs (NSAIDs) (coxibs). METHODS: MEDLINE search was performed using
      the key words "cyclooxygenase," "prostaglandin," "osteoarthritis" (OA), and
      "rheumatoid arthritis" (RA). Selected publications related to clinical trials
      with coxibs also are included. RESULTS: COX-2 is upregulated in inflamed joint
      tissues and is responsible for elevated PGE2 production. The overexpression of
      COX-2 is likely induced by proinflammatory mediators such as interleukin-1beta
      (IL-1beta) and tumor necrosis factor (TNF) alpha. However, the exact molecular
      mechanisms through which the expression of COX-2 is regulated remain to be
      elucidated. Several studies suggest that PGE2 is involved in inflammation,
      apoptosis, angiogenesis, and possibly structural changes that characterize
      arthritic diseases. NSAIDs are prescribed for the treatment of OA and RA and
      provide effective relief from symptoms; however, serious gastrointestinal
      complications occur with their use. The clinical efficacy of NSAIDs is primarily
      related to the inhibition of COX-2, whereas much of the toxicity is related to
      COX-1 inhibition. Selective COX-2 inhibitors (coxibs) that spare COX-1 at
      therapeutic doses are more effective than placebo and as effective as other
      NSAIDs for relief of symptoms of OA and RA, and have significantly improved
      gastrointestinal safety and tolerability. However, some studies showed that COX-2
      selective inhibitors still have classic NSAID complications. CONCLUSIONS:
      Overexpression of COX-2 protein in articular tissues is a characteristic feature
      of arthritic diseases. However, the molecular mechanisms involved in the
      regulation of COX-2 expression and activity are still unclear. Elucidating the
      mechanisms of COX-2 expression and PGE2 production and action will help identify
      novel and more selective potential drug targets in the treatment of arthritic
      diseases.

PMID- 14671727
TI  - Criteria for assessing pain and nonarticular soft-tissue rheumatic disorders of
      the neck and upper limb.
AB  - OBJECTIVE: To critically review the criteria used to diagnose nonarticular soft
      tissue rheumatic disorders of the neck and upper limb. METHODS: An extensive
      search of the literature, including a search of Medline and EMBASE, authoritative
      recent reviews, and relevant textbooks, was completed. The diagnostic criteria
      used in epidemiologic studies were compared and the reliability and validity of
      these criteria were assessed. RESULTS: Altogether, the search identified 117
      relevant research articles, among which 69 included a physical examination
      component, but few specified diagnostic criteria. Evidence supported respectable
      levels of between-observer repeatability regarding: symptom questionnaires
      (kappa, 0.52 to 0.79); measurement of shoulder range of motion with a goniometer
      (intraclass coefficients > 0.70); tests for carpal tunnel syndrome (Tinel's and
      Phalen's kappa, 0.53 to 0.80); and demonstration of neck tenderness (kappa =
      0.43). The Katz hand diagram, and combinations of physical signs of carpal tunnel
      syndrome, show reasonable sensitivity and specificity for that diagnosis but only
      among patients referred to specialists with that putative diagnosis; no such
      validity has been shown among the general population. Only 1 diagnostic
      examination schedule has published data on both the reliability and the validity
      of its criteria and diagnoses. For the remaining soft-tissue upper-limb
      disorders, diagnostic criteria rely apparently on face and content validity and
      reliability data have not been published. CONCLUSION: Classification of specific
      disorders of the neck and upper limb requires a back to basics approach. At
      present, the diagnosis of most of these conditions relies heavily on the clinical
      opinions of investigators and there are insufficient data to indicate that these
      criteria are repeatable, sensitive, or specific. Recent European initiatives
      offer scope to follow a more disciplined approach, but more work is urgently
      required.

PMID- 14671728
TI  - Soft-tissue rheumatic disorders of the neck and upper limb: prevalence and risk
      factors.
AB  - OBJECTIVES: To review the epidemiologic literature concerning the occurrence of
      and the risk factors for pain and specific soft-tissue rheumatic conditions that
      affect the neck and upper limbs. METHODS: An extensive search of the literature,
      including a search of Medline and EMBASE, authoritative recent reviews, and
      relevant textbooks, was performed. Studies that furnished data about the
      occurrence of or risk factors for regional pain or specific soft-tissue entities
      were extracted. RESULTS: Numerous epidemiologic studies among different
      populations suggest a high prevalence of pain in the neck (10% to 19%), shoulder
      (18% to 26%), elbow (8% to 12%), and wrist/hand (9% to 17%) at any point in time.
      Less clear is the proportion of pain caused by specific upper-limb disorders as
      compared with nonspecific pain; however, as many as 6% of adults may have carpal
      tunnel syndrome. Significant risk factors for these disorders include age, female
      gender, obesity, and association with mechanical exposures (eg, posture, force,
      repetition, vibration) in the workplace. Also implicated are psychologic well
      being and psychosocial workplace factors such as high levels of demand, poor
      control, and poor support. CONCLUSION: Pain and soft-tissue rheumatic disorders
      of the neck and upper limb are common. It appears that individual, mechanical,
      and psychosocial factors all contribute to upper-limb disorders, suggesting that
      future strategies for prevention will need to address each of these factors if
      they are to be successful.

PMID- 14671729
TI  - Human pythiosis, a rare cause of arteritis: case report and literature review.
AB  - OBJECTIVE: To present a case of Pythium insidiosum arteritis and review reported
      cases of human pythiosis. METHODS: Search of MEDLINE (PubMed) and the Thai Index
      Medicus was performed using the words "pythiosis" and "pythium." Search of
      abstracts from a scientific meeting also was performed. Only reported cases in
      the English or Thai language, with enough clinical information for analysis, were
      included. RESULTS: There were a total of 32 cases of human pythiosis, with 31
      identified in the literature. Twenty-five cases were Thai. Twenty of 21 patients
      with known occupations were farmers. There was ocular infection in 9 cases,
      subcutaneous infection in 5 cases, arterial infection in 17 cases, and
      cardiopulmonary infection in 1 case. Thalassemia was a common associated finding.
      In addition to systemic antifungal therapy, surgery was required in most cases.
      The highest mortality rate was seen in the arteritic form, particularly in
      patients with arterial lesions proximal to the superficial femoral artery.
      CONCLUSIONS: Human pythiosis is rare. Physicians should be suspicious of
      pythiosis in individuals, particularly farmers in Thailand, who develop
      nonhealing cutaneous ulcers or keratitis, which do not respond to conventional
      treatment. P insidiosum infections should be listed as a rare cause of infectious
      arteritis.

PMID- 14671730
TI  - Coercion and informed consent in research involving prisoners.
AB  - Prison-based research has been limited due to concern that prisoners may
      represent a vulnerable population secondary to possible coercion and limited
      capacity for voluntary informed consent. This study was designed to assess
      decisional capacity and susceptibility to coercion in prison research subjects.
      Subjects were 30 mentally ill prisoners and 30 healthy controls. The groups were
      compared on ability to provide informed consent to a hypothetical drug trial,
      susceptibility to possible coercion, neuropsychological functioning, and
      psychiatric symptoms. Results indicated that all controls and all but one of the
      prisoners demonstrated adequate capacity to consent to the hypothetical drug
      trial. However, when decisional capacity was measured quantitatively, prisoners
      performed significantly worse regarding two aspects of this ability. Regarding
      possible coercion, prisoners' main reasons for participating in research included
      avoiding boredom, meeting someone new, appearing cooperative in hopes of being
      treated better, and helping society. Neuropsychological functioning was strongly
      positively correlated with decisional capacity and negatively correlated with
      susceptibility to possible coercion, whereas psychiatric symptoms were only
      weakly correlated with these variables. In conclusion, a very high percentage of
      particularly vulnerable, mentally ill prisoners demonstrated adequate capacity to
      consent to research. Lower scores on a quantitative measure of decisional
      capacity suggest that extra care should be taken during the consent process when
      working with these subjects. The reasons prisoners gave for participating in our
      research indicated that the prison setting may have influenced their decision to
      participate, but that they were not actually coerced into doing so. Despite
      serious past incidents, ethicists will need to consider the possibility that
      prisoners have become an overprotected population.

PMID- 14671732
TI  - The relationship between insight and symptoms in schizophrenia.
AB  - We examined the relationship between insight and the positive, negative, active,
      dysphoric, and autistic dimensions of symptoms in patients with a diagnosis of
      schizophrenia. Ninety-six patients with a diagnosis of schizophrenia were
      assessed using the Scale to Assess Unawareness of Mental Disorder, Revised
      Version (SUMD-R) and the Positive and Negative Syndrome Scale (PANSS). The PANSS
      data were analyzed based on a five-factor model defined by White et al (1997).
      The percentage of patients having a lack of awareness was 32.7% for illness,
      58.2% for symptoms, 18.4% for treatment response, and 41.8% for social
      consequences. Lack of awareness of symptoms was significantly correlated with all
      five symptom factors. Lack of awareness of the illness and its social
      consequences was only correlated with the positive dimension. Lack of awareness
      of achieved effects of medication was correlated with the autistic preoccupation
      factor. There was no correlation between current misattributions for symptoms and
      PANSS factors. We conclude that poor insight is a common feature of schizophrenia
      and has a complex relationship to other symptoms of the illness. Our results
      suggest that (1) unawareness of symptoms is related to severity of illness; (2)
      insight into illness and its social consequences is more closely tied to positive
      symptoms than other aspects of insight; and (3) insight into the effects of
      medication is more closely related to cognitive impairment. Treatment studies
      that measure insight could answer the question of whether these deficits in
      awareness improve along with positive and cognitive symptoms.

PMID- 14671731
TI  - Insight in obsessive compulsive disorder and body dysmorphic disorder.
AB  - Similarities between obsessive-compulsive disorder (OCD) and body dysmorphic
      disorder (BDD) have been described in terms of clinical presentation, comorbidity
      rates, treatment response profiles, and other features. This is the first study
      to compare insight in OCD and BDD measuring global insight and numerous
      components of insight. We compared insight in 64 adult outpatients with DSM-IV
      OCD and 85 adult outpatients with DSM-IV BDD using a reliable and valid measure
      (the Brown Assessment of Beliefs Scale [BABS]). BDD patients had significantly
      poorer global insight than OCD patients. BDD patients also had significantly
      poorer insight on the following components of insight: conviction that the belief
      is accurate, perception of other's views of the belief, explanation for differing
      views, willingness to consider that the belief is wrong, and recognition that the
      belief has a psychiatric/psychological cause. Poorer insight was significantly
      positively correlated with more severe symptoms of the disorder only in the BDD
      group.

PMID- 14671733
TI  - Assessing personality features and their relations with behavioral problems in
      adolescents: Tridimensional Personality Questionnaire and Junior Eysenck
      Personality Questionnaire.
AB  - This study examines the applicability for adolescents of the Tridimensional
      Personality Questionnaire (TPQ), which was originally designed for adults, as
      compared to the Junior Eysenck Personality Questionnaire (JEPQ). The study also
      evaluates their inter-relationship and associations with various behavioral
      problems as reported by parents using the Child Behavior Checklist (CBCL). In a
      representative community sample of 905 adolescents, the results of internal
      consistency, test-retest reliability, and factor analysis showed that both the
      Harm Avoidance (HA) and the Novelty Seeking (NS) scales of the TPQ have sound
      construct validity, although the Reward Dependence (RD) scale has less so. The
      intercorrelation and factor analysis of the two questionnaires showed that the
      TPQ and the JEPQ are not simply alternative descriptions of the same construct of
      personality. In their associations with various behavioral problems, the scales
      of the TPQ are relatively more specifically associated with behavioral problems
      than the scales of the JEPQ. Our results provide empirical support for the
      applicability of the NS and the HA scales of the TPQ in adolescents, particularly
      in relation to behavioral problems.

PMID- 14671734
TI  - Impulsivity in patients with borderline personality disorder.
AB  - This study investigated features of impulsivity in patients with borderline
      personality disorder (BPD) using the self-report Attention-Deficit Scales for
      Adults (ADSA) and computer-administered neurocognitive tasks. Forty-one patients
      with DSM-III-R BPD and 35 nonclinical control subjects were assessed by the ADSA,
      the National Adult Reading Test, and two computerized tasks mediated by the
      frontal lobes. Mean scores for seven ADSA scales (six of which relate to aspects
      of impulsivity) were significantly higher in the patient group compared with the
      control group. Also, the ADSA ratings for impaired coordination were increased in
      the BPD patients. The findings indicate that a range of aspects of impulsivity,
      as well as impaired coordination, are associated with patients selected on the
      basis of BPD. Also, in the patient group, but not in the control group,
      associations of the neurocognitive tasks indicated that, first, performance on a
      planning task related to dorsolateral frontal lobe functioning is correlated with
      aspects of impulsivity reflected by ADSA scale III ratings (involving
      disorganisation and lack of perseverance) and, second, performance on a decision
      making task related to orbitofrontal functioning is correlated with ratings of
      impaired coordination. Further work is needed to establish the specificity of the
      findings.

PMID- 14671735
TI  - Personality-related characteristics in restricting versus binging and purging
      eating disordered patients.
AB  - The current study sought to examine differences in personality-related
      characteristics between restricting anorexia nervosa (RAN), binging/purging
      anorexia (BPAN), and purging bulimia nervosa (BN) patients. Scores on the
      Temperament and Character Inventory (TCI) and on the Dutch Eating Behaviour
      Questionnaire (DEBQ) were compared for 166 RAN, 78 BPAN, and 151 BN patients.
      Bingers/purgers showed a higher score for restrained, external and emotional
      eating and a lower score for a subscale of "self-directedness" compared to
      patients who never binge and purge. Personality differences were most marked
      between RAN and BN patients, while personality characteristics of BPAN patients
      tended to be similar to those of BN patients. BN patients showed higher scores on
      "novelty seeking" and the subscales "exploratory excitability," "impulsivity,"
      and "extravagance," and lower scores on "self-directedness," compared to
      restricting patients. Moreover RAN patients also showed higher scores on
      subscales of character dimensions, compared to BN patients. The higher the scores
      on novelty seeking, the lower the scores on several character scales, which has
      important implications for the reinforcement of behavior and the treatment of
      eating disorders.

PMID- 14671736
TI  - Peritraumatic dissociation as a predictor of post-traumatic stress disorder: a
      critical review.
AB  - In psychiatric literature, dissociative reactions at the time of a traumatic
      event (i.e., peritraumatic dissociation) are considered to be risk factors for
      the development of post-traumatic stress disorder (PTSD). In this article, we
      critically review research concerned with the link between peritraumatic
      dissociation and PTSD. Our main point is that studies in this area heavily rely
      on retrospective reports of dissociative reactions during the trauma. We argue
      that this methodology has important limitations since people in general and PTSD
      patients in particular find it difficult to give accurate descriptions of past
      emotional states. Restrictive factors that play a role in this context have to do
      with forgetting, attribution, and malingering.

PMID- 14671737
TI  - Alcoholism and seasonal affective disorder.
AB  - Seasonal changes in mood and behavior (seasonality) may be closely related to
      alcoholism. Some patients with alcoholism have a seasonal pattern to their
      alcohol misuse. They may be self-medicating an underlying seasonal affective
      disorder (SAD) with alcohol or manifesting a seasonal pattern to alcohol-induced
      depression. Both genetic and environmental factors play a role in the etiology
      and pathogenesis of alcoholism and SAD, operating, at least in part, through the
      brain serotonergic system. Family and molecular genetic studies suggest that
      there may be a genetic link between seasonality and alcoholism. Certain
      environmental and social factors may contribute to the development of seasonality
      in patients with alcoholism. The fact that SAD and alcoholism may be comorbid
      shows the importance of a thorough diagnostic interview. Both mental health and
      drug and alcohol professionals should be provided with education to assist with
      appropriate identification, management, and referral of patients presenting with
      comorbid alcoholism and SAD.

PMID- 14671738
TI  - The sensitivity of quality-of-life scale WHOQOL-100 to psychopathological
      measures in schizophrenia.
AB  - We aimed to investigate the reliability and the clinical sensitivity of the World
      Health Organization Quality of Life (WHOQOL-100) scale for patients diagnosed
      with schizophrenia because of its multilingual, multidimensional, and cross
      cultural properties. Fifty-four stabilized outpatients with schizophrenia and 49
      age-, sex-, and occupation-matched healthy control subjects were recruited. The
      scale showed high internal consistency (Cronbach alpha = 0.94). While there was
      no correlation between total scores of psychopathology measures (Brief
      Psychiatric Rating Scale [BPRS], Scale for the assessment of Negative Symptoms
      [SANS], Scale for the Assessment of Positive Symptoms [SAPS], and Clinical Global
      Impression [CGI]), significant negative correlations were obtained especially
      between subscales of the BPRS, SANS, SAPS, and QOL domains. Stepwise multiple
      regression analysis also revealed that the BPRS anxiety/depression and SANS
      anhedonia subcales were the predictor variables in five of six QOL domains in the
      schizophrenia group. The better quality-of-life scores of the mild group on
      physical and psychological domains indicate that the WHOQOL-100 could be used as
      an outcome measure in clinical studies. Thus, the WHOQOL-100 scale is a reliable,
      subjective quality-of-life scale for patients diagnosed with schizophrenia. The
      clinical sensitivity should also be assessed in large follow-up studies.

PMID- 14671739
TI  - Cincinnati criteria for mixed mania and suicidality in patients with acute mania.
AB  - The association between suicidality and diagnoses of mixed mania, as defined
      using both DSM-IV and Cincinnati criteria, was studied in 576 consecutive manic
      inpatients. Of the whole sample, 51 (8.9%) had suicidal ideation and 13 (2.3%)
      attempted suicide during the index episode. Suicidality was significantly more
      frequent in patients with a diagnosis of mixed mania, whether the diagnosis was
      made by DSM-IV or Cincinnati criteria. A multiple logistic regression analysis
      revealed that an additive combination of a diagnosis of mixed mania, the
      depression severity, and the Global Assessment of Functioning (GAF) score was
      significant in predicting suicidal ideation, when using the DSM-IV criteria. A
      diagnosis of mixed mania alone was significant in a similar analysis, when using
      the Cincinnati criteria. The adjusted odds ratio for a diagnosis of mixed mania
      to having suicidality was much higher when using the latter criteria (4.0 v
      14.0). A subsequent logistic regression analysis indicated that the Cincinnati
      mixed mania alone, rather than an additive combination of the DSM-IV mixed mania
      and the depression severity, achieved the most appropriate prediction of suicidal
      ideation in the sample. These findings did not differ, even when suicidality was
      defined as having a suicide attempt during the index episode. Our finding that
      suicidality was more strongly associated with Cincinnati mixed mania than with
      DSM-IV mixed mania is probably due to that suicidal patients who do not meet DSM
      IV criteria for mixed mania are classified into mixed mania, or/and that the
      depressive syndrome, related to suicidality, is more appropriately assessed among
      manic patients, when using the Cincinnati criteria. There was no evidence that
      marital status, employment, a lifetime history of alcohol or substance abuse, or
      a history of suicide attempts before the index episode was significantly
      associated with suicidality in the sample. Manic patients with suicidality may
      have a greater severity of residual depressive symptoms at discharge.

PMID- 14671740
TI  - Dissociative symptoms are related to endorsement of vague trauma items.
AB  - In current psychiatric literature, the received view is that dissociative
      symptoms originate from aversive childhood events. To a large extent, this view
      is based on cross-sectional studies that do not rule out a scenario in which
      dissociative tendencies contribute to self-reports of childhood trauma. In two
      studies, we tested one particular implication of this scenario, namely, that
      dissociative symptoms are related to endorsement of vague rather than specific
      items about childhood trauma. In study 1 (N = 43) and study 2 (N = 127),
      nonclinical participants completed standard measures of dissociation, childhood
      trauma, and fantasy proneness. We performed correlational and regression analyses
      on the data. Fantasy proneness and responses to broad trauma items, but not
      responses to factual trauma items predicted dissociation levels. This pattern of
      findings shows that the link between trauma and dissociation is considerably more
      complex than is often assumed. As well, it suggests that at least in nonclinical
      samples, dissociative symptoms may breed endorsement of vague trauma items.

PMID- 14671741
TI  - Loose nuts.

PMID- 14671742
TI  - [The importance of Medical School of Universidade Estadual do Ceara].

PMID- 14671743
TI  - [The importance of PCR in hepatitis C for blood donors triage].

PMID- 14671744
TI  - NPs speak out about the less fortunate.

PMID- 14671745
TI  - NPs speak out about the less fortunate.

PMID- 14671746
TI  - [Better evaluation of diagnostic tests].

PMID- 14671747
TI  - [Role of the biologist in the study of schistocytes].
AB  - The appearance of schistocytes in a peripheral blood film is considered to be an
      important diagnostic marker for thrombotic microangiopathy. However, the
      morphological analysis of schistocytes remains uneasy. To determine practice
      patterns in the biological management of schistocytosis, the French Group of
      Cellular Hematology from the French Society of Hematology conducted a survey on
      the approach of the diagnosis of microangiopathy. A guideline is proposed in
      order to cancel the substantial variation among biologists.

PMID- 14671748
TI  - [New diagnostic approaches in malignant B-cell lymphomas].
AB  - The new WHO classification of B-cell neoplasms published in 2001 gathers
      leukaemia and lymphoma. This classification highlights the stage of
      differentiation of the tumour cell. It groups B-cell neoplasms morphology,
      histology (nodular or diffuse pattern, cell morphology), immunophenotypes,
      cytogenetic, molecular abnormalities and clinical data. Recent advances of the
      normal B cell differentiation understanding and the development of new types of
      analysis have shown that mature B-cell neoplasms appear to recapitulate stages of
      normal B-cell differentiation, leading to such a new classification.

PMID- 14671749
TI  - [Preimplantation genetic diagnosis of monogenic diseases].
AB  - Preimplantation genetic diagnosis (PGD) is an alternative to prenatal diagnosis
      allowing the detection of genetic diseases on IVF embryos before their transfer
      into the uterus and before the pregnancy. The aim of this procedure is to obtain
      unaffected or carrier embryos in order to avoid the burden of termination of
      pregnancy after prenatal diagnosis for couples at risk of transmitting
      particularly severe genetic disorders to their offspring. For monogenic diseases,
      PGD is most often based on single blastomere amplification by polymerase chain
      reaction (PCR). More than a decade after the first births, the possibilities of
      diagnosis for monogenic diseases have considerably increased. As for molecular
      biology and conventional diagnosis, the technologies and strategies for PGD are
      continually improved, with for instance introduction of fluorescent PCR or
      multiplex amplification. In this review, we describe several approaches for PGD
      of monogenic diseases, followed by an overview of the French practice,
      particularly in our lab.

PMID- 14671750
TI  - [Hormone determination in the management and monitoring of cycles of medically
      assisted reproductive technology: value and difficulties of use].
AB  - In assisted reproductive technology (ART), serum levels of several key hormones
      are used to evaluate ovarian follicular reserve and to monitor gonadotropin
      stimulated follicle growth. Currently, serum estradiol, FSH, LH and inhibin B
      levels are examined and combined at the beginning of the menstrual cycle to
      evaluate the functional status of the ovaries, providing information for
      appropriate ovarian stimulation treatment and prognosis for in vitro
      fertilization (IVF) outcome. In women undergoing in vitro fertilization and
      embryo transfer (IVF-ET), ovulation stimulation is monitored by serial
      measurements of estradiol, progesterone and LH to monitor follicular growth,
      evaluate the progression of stimulation, adjust daily gonadotropin therapy for
      each patient, and predict the optimal day for the induction of ovulation. We
      analyze the importance of each hormone and discuss the discrepancies frequently
      reported resulting from differences in methods.

PMID- 14671751
TI  - [West African tick-borne relapsing fever].
AB  - West African tick-borne relapsing fever is an endemic disease due to Borrelia
      crocidurae. The tick Alectorobius sonrai is the only known vector of this
      bacterium. Several species of rodents and insectivores may be reservoir for this
      spirochete. The geographic distribution of Borrelia crocidurae is not well known.
      The zone where the presence of the vector has been recorded is situated in
      Sahelian regions, from Mauritania and northern Senegal up to Chad. In Senegal, it
      has been shown that the persistence of drought is responsible for a considerable
      spread of tick-borne relapsing fever to the south. Few epidemiological data are
      available about West African tick-borne relapsing fever. In Senegal,
      epidemiological investigations indicate that Borrelia crocidurae is a major cause
      of morbidity (annual incidence rate of 5.1%). The relapsing nature of tick-borne
      borreliosis depends on Borrelia's antigenic variability. Except relapsing febrile
      episodes, this illness presents no pathognomonic signs. Borrelia crocidurae
      relapsing fever is generally benignant but neurologic or ocular complications can
      occur. The diagnosis of tick-borne relapsing fever is made by demonstrating the
      presence of Borrelia in peripheral blood in thick smear, by intraperitoneal
      inoculation of mice or more recently with quantitative buffy coat method (QBC
      test). The best treatment for relapsing fever is tetracycline or doxycycline.
      When tetracyclines are contraindicated, the alternative is erythromycin. In
      neurologic complications, the effective treatment is intravenous penicillin G or
      ceftriaxone. West African tick-borne relapsing fever must be systematically
      mentioned in case of fever in a patient returning from the endemic area.

PMID- 14671752
TI  - [HDL-cholesterol: role of its dosage in the assessment of cardiovascular risk].
AB  - The interest of HDL-cholesterol (HDLC) to evaluate a cardiovascular risk has been
      studied since many years. According to Framingham Heart studies, this factor is
      inversely correlated to a future ischaemic heart disease. At high level, HDLC is
      considered as a cardiovascular protecting factor, and is known since few years as
      "good cholesterol". In the year 2000, the ANAES (Agence nationale de
      l'accreditation et evaluation en sante) has redefined the role of HDLC in the
      exploration of dyslipidaemia. In the case of a cardiovascular-risk history, HDLC,
      with total cholesterol, triglycerides, and LDL-cholesterol (by Friedewald method)
      will be analyzed. Usually, HDLC is not very accessible to conventional
      treatments. So, according to ANAES, the treatment of dyslipidaemia will be based
      on LDL-cholesterol levels only. Nevertheless, HDLC is a major lipid factor to
      evaluate a cardiovascular risk. The object of this review is, on one hand, to
      situate HDLC in the evaluation of cardiovascular risk, by showing its key role in
      lipid metabolism, and, on the other hand, to report the main direct assays of
      this parameter.

PMID- 14671753
TI  - [Serum protein electrophoresis: comparison of capillary zone electrophoresis
      Capillarys (Sebia) and agarose gel electrophoresis Hydrasys (Sebia)].
AB  - Since several years, serum proteins electrophoresis became a routine analysis,
      mainly performed by agarose gel electrophoresis, frequently semi-automated. We
      compared the new fully automated capillary electrophoresis system from Sebia,
      Capillarys, with our reference method, agarose gel electrophoresis Hydrasys
      (Sebia). This study focused on the evaluation of both the analytical performances
      and some practical aspects such as ease of use, rapidity, costs. It appears
      clearly from that study that both methods give similar results for the detection
      of monoclonal proteins. We notice that the capillary electrophoresis (Capillarys)
      displays higher sensitivity (97.2%) than the agarose gel electrophoresis Hydrasys
      (93.5%), however with a lower specificity (93.7 versus 98.9%). On the other hand,
      the Capillarys method displays obvious practical advantages such as full
      automation, ease of use and rapidity.

PMID- 14671754
TI  - [Diagnosis and biological monitoring of 6 neurosyphilis cases: value of
      cerebrospinal fluid analysis].
AB  - Our objective is to assess the relevance of the different laboratory findings in
      cerebrospinal fluid (CSF) and serum for the diagnosis and survey of active
      neurosyphilis. A retrospective study of six hospitalized neurosyphilitic patients
      at Neurological Hospital of Lyon from 1987 to 2002 was carried out. Six males
      were found, aged from 29 to 72 years. Neurosyphilis can be group in two
      categories: early (meningeal and meningovascular neurosyphilis) and late
      (progressive general paralysis and tabes dorsalis). All were tertiary stage and
      HIV negative. We performed in CSF, white and red cell count, cytology, total
      protein, glucose levels, in CSF and serum, albumin, total IgG, IgA, IgM for
      calculation of albumin quotient and IgG, IgA and IgM index. Serological tests for
      syphilis in CSF and serum are VDRL and TPHA. To increase the reliability of
      treponema antibody tests, the ratio of serum-to-CSF content of albumin is used to
      assess intrathecal production of treponema antibodies, especially the treponema
      pallidum hemagglutination assay (TPHA index). The CSF changes in neurosyphilis
      included elevated cell count with lymphocytic-plasmocytic cell reaction,
      increased protein content, strongly positive IgG index, numerous positive IgG
      oligoclonal bands, positive blood and CSF serology. Serological tests are
      difficult to interpret. Examination of CSF played a major role in the diagnosis
      and treatment of all forms of neurosyphilis. The CSF abnormalities improved with
      clinical improvement, especially in meningeal and vascular neurosyphilis, but the
      response in paresis and tabes was slower or nonexistent. Pleocytosis and protein
      are indicators of inflammatory activity in the central nervous system and are
      used as a clinical guide in the diagnostic, for treatment and re-treatment.

PMID- 14671755
TI  - [Contribution of the laboratory to the evaluation of brain-dead patients for
      obtaining organs from dead individuals].
AB  - The removal organ in order to transplantation is realized often for patient
      deceased. It was regulation activity that passes in urgency context where
      laboratory play an important role. The biochemistry, immunology, haematology,
      toxicology and microbiology analysis allows the validation of the donors, the
      supervision of the functional quality of organ and the definition of the best
      couple donor-recipient.

PMID- 14671756
TI  - [Evaluation of the blood analyzer Beckman Coulter LH 750: analytic performance,
      decision rules].
AB  - We evaluated the new analyzer Beckman Coulter, an instrument dedicated to the
      cell blood count (CBC) and to the white blood cell (WBC) differential (including
      nucleated red blood cells (NRBCs)) over a global one month period, with three
      purposes: 1) evaluation of the analytical performance (precision,
      reproducibility, contamination, linearity); 2) accuracy of numerical results, by
      comparison to the laboratory instrument (CBC and WBC diff) or to the blood smear
      (NRBCs, low platelets); 3) evaluation, in terms of sensitivity and specificity, a
      set of abnormality messages built from the suspect flags and a few quantitative
      abnormalities. The analytical performances were found satisfactory. The WBC and
      platelet ranges of linearity were wider than in the GEN.S, as stated in the
      system specifications. However, the lack of adequate biological material made
      impossible the study of the whole mentioned linearity range. The accuracy of the
      CBC and differential parameters, as well as of reticulocytes, was studied with
      the Coulter GEN.S as reference instrument. The coefficients of correlation and
      the regression lines showed that the LH 750 results were similar to the GEN.S
      results. Furthermore, samples with thrombocytopenia and circulating NRBCs were
      evaluated and compared to the result obtained with microscopic lecture. The
      results showed a good relationship between platelets results given by the GEN.S
      and manual count leading to appropriate decision of transfusion. The correlation
      between GEN.S and manual count of NRBC was estimated as satisfactory. We used the
      LH 750 software to create conditional rules on the basis of qualitative and
      quantitative criteria, in order to define and enter a message system for
      detection of abnormalities. Our study showed that such a system flagged 95.7% of
      morphological abnormalities with a rate of unnecessary slide review (absence of
      any morphological abnormality on the blood smear) estimated at 8.3%. Furthermore,
      in 86% of the abnormalities studied, the relevant message was triggered. The
      Beckman Coulter LH 750 thus appeared as suitable in terms of validation
      efficiency.

PMID- 14671757
TI  - [A fatal case of Herpes simplex virus meningoencephalitis in an immunocompetent
      adult].
AB  - Management of herpes simplex virus encephalitis (HSE) has been considerably
      improved by the development of rapid polymerase chain reaction (PCR) assays and
      by the use of intravenous acyclovir. However, an absence of early antiviral
      treatment has been associated to a poor outcome in patients with HSE. In the
      present report, we described the case of a 53 years-old adult immunompetent
      patient who was admitted to the emergency department of university medical center
      of Reims (France). At the time of hospitalisation, he was suffering from a
      febrile encephalitis syndrome evolving for more than 24 hours. A cerebrospinal
      fluid (CSF) puncture was performed demonstrating the presence of a lymphocytic
      meningitidis (42 leukocytes/mm3 which 90% of mononuclear cells; CSF protein =
      1650 mg/L) associated with high levels of interferon alpha (75 UI/mL). Specific
      herpesvirus PCR and hybridisation assays (Herpes Consensus Hybridowell, Argene,
      France) were positive for the detection of HSV-1 genome on this CSF sample.
      Despite the intravenous acyclovir treatment (15 mg/kg/8 hours) delivered at the
      time of hospitalisation, this immunocompetent adult patient will dead 15 days
      later by a cardiorespiratory failure that was related to extensive HSE lesions.
      The time delay between the beginning of the clinical syndrome and the
      instauration of intravenous acyclovir treatment (more than 24 hours) was the only
      point susceptible to explain the presence of extensive CNS lesions in this
      patient. Specific Herpesvirus PCR detection assays are powerful tools that are
      actually used to establish a rapid etiological diagnosis of viral meningo
      encephalitis. However, in patients demonstrating clinical signs of encephalitis
      associated with an aseptic CSF, it remains essential to urgently initiate a
      presumptive intravenous acyclovir treatment (10-15 mg/kg/8 hours). Actually, this
      medical practice is the only one susceptible to reduce the morbi-mortality rates
      linked to HSE.

PMID- 14671758
TI  - [Risk of underestimating platelet count because of the increase of mean platelet
      volume at the end of pregnancy].
AB  - We report the case of a pregnant woman for whom the platelet count (77 x 10(9)/L)
      was underestimated by Coulter STKS analyzer during the third trimester because of
      large platelets. The microscopic counting of platelets revealed an isolated
      thrombocytopenia (120 x 10(9)/L). When not pregnant, the patient has low but
      normal platelet count (155 x 10(9)/L) with high mean platelet volume (MPV > 12
      fL). This case report recalls that concomitantly to the decrease in platelet
      count, the MPV significantly increases at the end of pregnancy. This poorly known
      phenomenon does not impair platelet count by blood cell analyzers in as much as
      the platelet volume is in the range of measurement but may be responsible for
      underestimation of the platelet count if the MPV is already high before
      pregnancy. We describe how to detect this anomaly and propose simple guidelines
      for thrombocytopenia in normal pregnancy.

PMID- 14671759
TI  - [Difficult diagnosis of autoimmune peripheral neuropathy].

PMID- 14671760
TI  - [Evaluation of a functional test in the screening of protein S deficiency].

PMID- 14671761
TI  - [Call for researchers associated with a biological study of neural tube defects:
      prospective study of the role of homocysteine in neural tube defects in France].

PMID- 14671762
TI  - [Concordance between serum levels of vitamin B12 and clinicobiological signs of
      deficiency].

PMID- 14671763
TI  - [Analytical performance of troponin Ic determination with the ACS 180 SE (Bayer
      Diagnostics)].

PMID- 14671764
TI  - Ethnicity and the politics of the new genetics: principles and engagement.
AB  - Identifying the genetic basis of disease is not a straightforward medical
      procedure but implicates the broader social, cultural and political context.
      Ethnicity represents an important part of this context, particularly given the
      confused and poorly informed debate about genetic differences among supposedly
      different 'racial' populations. Debates about the 'new genetics', however, have
      not engaged fully with the issue of ethnicity and racism. This paper, by
      reviewing a mix of empirical and theoretical debates, explores the discursive
      practices that inform current thinking on genetics, ethnicity and race. The
      account begins by exploring some of the philosophical tensions inherent in
      providing genetic testing. In doing so, the paper argues that current debates
      about genetics are not neutral but evoke a specific set of received ideas and
      codes of intervention, embodying social and power relationships. The paper then
      broadens the discussion by exploring the general meaning of screening and
      counselling for the 'lay' population, before focusing on the process of providing
      information and identifying people as carriers. The paper concludes by suggesting
      that the social space in which the 'new genetics' is enacted, understood and
      given meaning raises generic concerns, irrespective of ethnicity. These include
      the potential tension between prevention and informed decision making, whereby
      ideas about empowering individuals to exercise choice exist alongside a more
      general societal concern with minimising impairment and illness. In more
      practical terms, individual choice is compromised by poor-quality care,
      inadequate information, insensitivity to an individual's worries and concerns and
      a more general failure to meet his or her needs. At the same time, however, the
      often racialised perspectives articulated through the activities of service
      professionals can further complicate the choices and decisions available to
      minority ethnic populations. The failure to recognise and respond to diversity;
      blaming minority ethnic populations for their health problems; and the
      pervasiveness of racist myths and stereotypes in service provision, serve to
      disadvantage minority ethnic populations. This explains why themes such as equity
      and access, political engagement as well as more general notions of deservingness
      based on the construction of citizenship and identity emerge as fundamental in
      making sense of the relationship between ethnicity and the politics of the 'new
      genetics'.

PMID- 14671765
TI  - Renal transplantation for Indigenous Australians: identifying the barriers to
      equitable access.
AB  - OBJECTIVE: To assess Indigenous Australians' access to renal transplantation,
      compared with non-Indigenous Australians. To examine whether disparities are due
      to a lower rate of acceptance onto the waiting list and/or a lower rate of moving
      from the list to transplantation. DESIGN: National cohort study using data from
      the Australian and New Zealand Dialysis and Transplant Registry. We included all
      end-stage renal disease (ESRD) patients under 65 years of age who started
      treatment in Australia between January 1993 and December 1998. We used survival
      analysis to examine the time from commencement of renal replacement therapy (RRT)
      to transplantation. We measured time from commencement of RRT to acceptance onto
      the waiting list (stage 1), and time from acceptance onto the waiting list to
      transplantation (stage 2). The main outcome measures were (1) acceptance onto the
      waiting list and (2) receipt of a transplant, before 31 March 2000. RESULTS:
      Indigenous patients had a lower transplantation rate (adjusted Indigenous: non
      Indigenous rate ratio 0.32, 95% CI 0.25-0.40). They had both a lower rate of
      acceptance onto the waiting list (adjusted rate ratio 0.50, 95% CI 0.44-0.57) and
      a lower rate of moving from the list to transplantation (adjusted rate ratio
      0.50, 95% CI 0.38-0.65). The disparities were not explained by differences in
      age, sex, co-morbidities or cause of renal disease. CONCLUSIONS: Indigenous
      Australians face barriers to acceptance onto the waiting list and to moving from
      the list to transplantation. Further research to identify the causes could
      facilitate strategies to improve equity in transplantation.

PMID- 14671766
TI  - Evaluation of equity in diabetes health care in relation to African and Caribbean
      ethnicity.
AB  - OBJECTIVE: Many US studies have shown that ethnic minority groups have less
      access to health care. We evaluated whether black African and black Caribbean
      people with diabetes in the UK gain access to diabetes health care on an
      equitable basis compared with white people. DESIGN: Cross-sectional questionnaire
      survey set in 29 general practices in south London. Main measures were self
      reported morbidity, SF-36 scores and utilisation of health care. Analyses of
      utilisation variables were adjusted for age, sex, ethnic group, duration of
      diabetes, and socio-economic and health status. RESULTS: There were 1,899
      respondents (64%) from 2,983 individuals registered with diabetes. These included
      799 white, 522 black Caribbean, 163 black African and 415 other subjects with
      type 2 diabetes. After adjusting for need, black Caribbeans reported higher
      utilisation of health care than white subjects for four of nine utilisation
      variables, and black Africans for two. For the remaining variables utilisation
      was equivalent in different ethnic groups. Black Caribbean subjects were more
      likely to be treated for hypertension if hypertensive (odds ratio 1.84, 95% CI
      1.05 to 3.22), to use blood or urine self-monitoring (1.40, 1.04 to 1.88) and to
      have attended a diabetes nurse (1.34, 1.04 to 1.74) or dietician (1.49, 1.19 to
      1.86). Black Africans were more likely to have attended a dietician (2.15, 1.40
      to 3.29) or an ophthalmologist (1.72, 1.10 to 2.70) in the past year. CONCLUSION:
      There was no evidence from this study that black African or black Caribbean
      subjects had less access to diabetes health care in relation to need.

PMID- 14671767
TI  - Elderly care for ethnic minorities--wishes and expectations among elderly Finns
      in Sweden.
AB  - OBJECTIVES: Although elderly people from immigrant and minority groups utilise
      elderly care facilities to a lesser extent than elderly people from majority
      groups, there is a lack of research on how elderly people with different ethnic
      backgrounds wish and expect to be cared for when they are in need of
      institutional elderly care. This study aims to illuminate the role that
      culturally appropriate care plays in elderly Finnish immigrants' wishes and
      expectations of institutional elderly care in Sweden. DESIGN: Thirty-nine elderly
      Finnish immigrants in Sweden, aged 75 years or more, were interviewed in their
      homes. The data were analysed with latent qualitative content analysis. RESULTS:
      The elderly Finnish immigrants in Sweden wished to be able to continue living in
      their current homes for as long as possible. Later on, when entering
      institutional elderly care, they wanted to feel continuity, familiarity, security
      and companionship with others. As immigrants, they had to choose to be cared for
      either in well-known physical environments close to their current homes, or in a
      culturally appropriate care setting with familiar socio-cultural conditions.
      CONCLUSIONS: To be able to provide institutional elderly care for minority groups
      it is important to ease the access to elderly care amenities by providing care
      that results in maintaining as much continuity and familiarity as possible in the
      lives of the elderly people. This includes the care providers and other residents
      who share the familiar aspects of their lives. This involves providing culturally
      appropriate elderly care close to the elderly people's current homes.

PMID- 14671768
TI  - Assessing the reliability and validity of the John Henry Active Coping Scale in
      an urban sample of African Americans and white Americans.
AB  - OBJECTIVES: The primary focus of this study was to examine the psychometric
      properties of the John Henry Active Coping scale (JHAC12) among an urban middle
      aged sample of African Americans and white Americans. DESIGN: The sample
      consisted of 75 African Americans and 129 white Americans from South Florida
      ranging in age from 25 to 54 years. Subjects completed the JHAC12, the Life
      Orientation Test (LOT), Coping Orientation to Problems Encountered (COPE)
      subscales, and the Marlowe-Crowne Social Desirability scale. RESULTS: Major
      findings supported the validity and reliability of the JHAC12 among both African
      Americans and white Americans. For both the African American and white American
      subsamples, the JHAC12 was correlated with the active coping and suppression of
      competing activities subscales of the COPE and negatively correlated with the
      Marlowe-Crowne Social Desirability scale. In the African American subsample the
      JHAC12 was positively correlated with the LOT. The JHAC12 was also negatively
      associated with the behavioral disengagement subscale of the COPE among white
      Americans. Multiple regression analyses revealed that the proportion of variance
      in the JHAC12 explained by the various subscales of the COPE, Marlowe-Crowne, and
      the LOT was 43% for African Americans and 20% for white Americans. Factor
      analyses suggested two similar and meaningful factors among the African American
      and white American subsamples. Finally, Cronbach alpha reliabilities revealed
      similar subsample coefficients. DISCUSSION: The implications of the findings are
      discussed in terms of the JHAC12's ability to assess the construct of active
      coping among African Americans and white Americans.

PMID- 14671769
TI  - Infant botulism: a diagnostic and management challenge.

PMID- 14671770
TI  - Stress, burnout, and social support: a review and call for research.

PMID- 14671771
TI  - The Air Medical Leadership Congress: setting the health care agenda for the air
      medical community.
AB  - BACKGROUND: Emergency air medical transport provides the means for critically ill
      or injured patients to rapidly access sophisticated medical flight teams and
      medical centers. However, issues such as surging emergency medical services
      helicopter accidents, expected pilot and nurse shortages, falling reimbursements,
      and new compliance regulations are now threatening these important but expensive
      transport services. Unless an industry strategy can be developed to address these
      and other threats, many medical flight programs may be forced to curtail the
      availability of these lifesaving services. PURPOSE: On September 4-6, 2003, air
      medical leaders, experts, program managers, providers, and users of emergency air
      medical services gathered in Salt Lake City, Utah, to discuss and formulate
      recommendations to address the top issues that threaten the future of air medical
      transport services. This congress was open to anyone engaged in the field of air
      medical transport. This historic meeting resulted in a plan to enhance transport
      safety, foster appropriate utilization, improve in-flight medical care, maximize
      cost and reimbursement effectiveness, and develop strategies to reduce the
      adverse effects of new regulatory and compliance mandates. OBJECTIVES: This
      article describes the significance of the Air Medical Leadership Congress and the
      10-Point Plan method used to develop it.

PMID- 14671772
TI  - A case of blunt cardiac rupture.

PMID- 14671773
TI  - Interfacility transport of patients admitted to the ICU: perceived needs of
      family members.
AB  - INTRODUCTION: Limited research has been published regarding the needs of
      immediate family members with respect to the transport of critically ill loved
      ones. Furthermore, very little information exists on transport teams members'
      perception of the needs of the family members. METHODS: During a 9-month period,
      a 25-item questionnaire was given to family members of adult patients who were
      transported by air or ground. All patients were admitted into an adult intensive
      care unit at a major university teaching hospital. Family members were asked to
      rank the relative importance of each item with regard to informational or
      situational needs. The identical questionnaire was given to the critical care
      transport teams employed by the hospital. The team members were asked to indicate
      what they thought the family members ranked as important. RESULTS: Forty-two of
      100 family members (42%) returned the questionnaire by mail. All 13 (100%)
      critical care transport team members completed surveys as well. Statistical
      comparisons indicated that family members and team members differed significantly
      on 13 of 25 items. Team members generally underestimated the importance of these
      items to family members. CONCLUSION: These findings suggest that, in this sample,
      transporting crew members often misperceived family members informational and
      situational needs.

PMID- 14671774
TI  - Stem cell plasticity, cell fusion, and transdifferentiation.
AB  - One of the most contentious issues in biology today concerns the existence of
      stem cell plasticity. The term "plasticity" refers to the capacity of tissue
      derived stem cells to exhibit a phenotypic potential that extends beyond the
      differentiated cell phenotypes of their resident tissue. Although evidence of
      stem cell plasticity has been reported by multiple laboratories, other scientists
      have not found the data persuasive and have remained skeptical about these new
      findings. This review will provide an overview of the stem cell plasticity
      controversy. We will examine many of the major objections that have been made to
      challenge the stem cell plasticity data. This controversy will be placed in the
      context of the traditional view of stem cell potential and cell phenotypic
      diversification. What the implications of cell plasticity are, and how its
      existence may modulate our present understanding of stem cell biology, will be
      explored. In addition, we will examine a topic that is usually not included
      within a discussion of stem cell biology--the direct conversion of one
      differentiated cell type into another. We believe that these observations on the
      transdifferentiation of differentiated cells have direct bearing on the issue of
      stem cell plasticity, and may provide insights into how cell phenotypic
      diversification is realized in the adult and into the origin of cell phenotypes
      during evolution.

PMID- 14671775
TI  - Hematopoietic stem cells.
AB  - Considerable effort has been made in recent years in defining the embryonic
      origin of the hematopoietic stem cell (HSC). Using transgenic mouse models, a
      number of genes that regulate the formation, self-renewal, or differentiation of
      HSCs have been identified. Of particular interest, it has recently been shown
      that key regulators of definitive blood formation played a crucial role in adult
      HSC development. Specifically, the use of some of these regulatory molecules has
      dramatically improved the potential of adult HSC expansion. Furthermore, the
      elucidation of the molecular phenotype of the HSC has just begun. Finally,
      unexpected degrees of HSC developmental or differentiation plasticity have
      emerged. In this review, we will summarize the recent advances made in the human
      HSC field, and we will examine the impacts these discoveries may have clinically
      and on our understanding of the organization of the human hematopoietic system.

PMID- 14671776
TI  - Muscle-derived stem cells: potential for muscle regeneration.
AB  - Duchenne muscular dystrophy (DMD) is a devastating X-linked muscle disease
      characterized by progressive muscle weakness caused by the lack of dystrophin
      expression at the sarcolemma of muscle fibers. Although various approaches to
      delivering dystrophin in dystrophic muscle have been investigated extensively
      (e.g., cell and gene therapy), there is still no treatment that alleviates the
      muscle weakness in this common inherited muscle disease. The transplantation of
      myoblasts can enable transient delivery of dystrophin and improve the strength of
      injected dystrophic muscle, but this approach has various limitations, including
      immune rejection, poor cellular survival rates, and the limited spread of the
      injected cells. The isolation of muscle cells that can overcome these limitations
      would enhance the success of myoblast transplantation significantly. The
      efficiency of cell transplantation might be improved through the use of stem
      cells, which display unique features, including (1) self-renewal with production
      of progeny, (2) appearance early in development and persistence throughout life,
      and (3) long-term proliferation and multipotency. For these reasons, the
      development of muscle stem cells for use in transplantation or gene transfer (ex
      vivo approach) as treatment for patients with muscle disorders has become more
      attractive in the past few years. In this paper, we review the current knowledge
      regarding the isolation and characterization of stem cells isolated from skeletal
      muscle by highlighting their biological features and their relationship to
      satellite cells as well as other populations of stem cells derived from other
      tissues. We also describe the remarkable ability of stem cells to regenerate
      skeletal muscle and their potential use to alleviate the muscle weakness
      associated with DMD.

PMID- 14671777
TI  - Cell-based therapies for birth defects: a role for adult stem cell plasticity?
AB  - Cell therapy can offer a reasonable approach to the treatment of specific birth
      defects, particularly those for which hematopoietic stem cells (HSCs) can be used
      to restore (even partially) the number of cells, protein levels, or enzyme
      activity. Relatively few clinical experiences have been published on this
      subject, but when a natural selective advantage exists for the cell graft, a
      degree of "rescue" is possible. Strategies have been developed to confer a
      selective advantage through genetic engineering of donor cells, and this approach
      may prove valuable in the treatment of birth defects, as it is in hematological
      malignancy. Stem cell (SC) plasticity, or transdifferentiation, may offer another
      route for delivery of cells to established or developing organs. A wide variety
      of studies support the concept that adult tissue-specific SCs can, if displaced
      from their normal niche to another, be reprogrammed to produce cell types
      appropriate to their new environment. Clinical observations reveal that
      persistent tissue microchimerism develops not only in blood lineages after
      transfusion, but also in thyroid follicular epithelium via transplacental
      exchange. In addition, hepatic and renal parenchyma also become chimeric
      following allografts or bone marrow transplantation (BMT). Experimental models
      indicate that a renal glomerulosclerosis phenotype can be transferred by grafting
      whole BM, and that a severe liver disorder in fah-/- mice can be overcome by
      grafting HSCs and then exerting a selection pressure. It may be possible in the
      future to exploit the ability of adult SCs to contribute to diverse tissues;
      however, our understanding of the processes involved is at a very early stage.

PMID- 14671778
TI  - Biology and clinical applications of mesenchymal stem cells.
AB  - Stem cell populations are found in most adult tissues and, in general, their
      differentiation potential may reflect the local cell population. Hematopoietic,
      epidermal, mesenchymal, neural and hepatic stem cells have been described. It may
      be that, in the adult, these cells are the reservoirs of reparative cells that
      are mobilized following injury and migrate to the wound site where, in
      cooperation with local cells, they participate in the repair response.
      Mesenchymal stem cells, isolated from the bone marrow, have the capacity to
      differentiate into cells of connective tissues. Some striking examples of the
      therapeutic use of MSCs have been reported recently in applications such as
      coronary artery disease, spinal cord injury, Parkinson's Disease, and liver
      regeneration. In orthopaedic medicine, MSC therapy has been applied in bone and
      cartilage repair and in the treatment of osteoarthritis. The question of the host
      response to implanted MSCs is critical as these cells are being evaluated in
      clinical applications. There are several aspects to the implanted cell-host
      interaction that need to be addressed as we attempt to understand the mechanisms
      underlying stem cell therapies. These are (1) the host immune response to
      implanted cells, (2) the homing mechanisms that guide delivered cells to a site
      of injury, and (3) differentiation of implanted cells under the influence of
      local signals.

PMID- 14671779
TI  - [Chemotherapy and surgery in the treatment of liver metastasis of colorectal
      cancer: a sacred union...].

PMID- 14671780
TI  - [New surgical strategies for liver metastasis of colorectal cancer: report of 3
      cases].

PMID- 14671781
TI  - The continuum of dental education and its environment.

PMID- 14671782
TI  - PCD reforms afoot.

PMID- 14671783
TI  - Registration & revalidation. What next?

PMID- 14671784
TI  - Good practice.

PMID- 14671785
TI  - Educational needs of dental trainers.

PMID- 14671786
TI  - Satisfactory completion of dental vocational training in Scotland: a system of
      assessment.
AB  - Formal assessment of dental vocational training (DVT) has been an issue since
      1993 when DVT became mandatory for graduates wishing to practice within the NHS.
      There have been a number of other drivers for change, including concerns about
      the capabilities of new graduates, a lack of standardisation of the training
      experience and accountability for standards of training. All of these factors
      contributed to the decision, by the Scottish Council for Postgraduate Medical and
      Dental Education (now part of NHS Education for Scotland--NES), to support a
      programme of research into the development of a competency-based system of
      assessment for DVT. During the life of this project the argument for introducing
      assessment of DVT and General Professional Training (GPT) has become ever
      stronger.

PMID- 14671787
TI  - Senior house officer training in oral and maxillofacial surgery: a national
      survey.
AB  - Service commitments have often taken priority over training for many senior house
      officers. There have been changes, with more planned to make this truly a
      training grade. We conducted a national postal survey of senior house officers
      (SHO) in oral and maxillofacial surgery (OMFS) in 2001/2002. A total of 229
      replies were received with an estimated response rate around 70%. Almost 60% of
      these respondents (57.2%) had been a SHO in OMFS for over 3 years. Only 39% had a
      weekly bleep-free teaching session. Forty-eight per cent did not think
      undergraduate BDS training was adequate for their job. This 48% of SHOs were
      significantly less likely to have out patient clinic sessions with a designated
      trainer undertaking teaching (chi 2 = 6.127, P = 0.013) or have a bleep-free
      teaching session (chi 2 = 6.896, P = 0.009). Sixty-four per cent had received
      formal training in medical examination of patients. Twenty-nine per cent had not
      been appraised during their present post. Forty-two per cent of SHOs in OMFS are
      in band 3 posts. Improvements have been made, but there is a case for further
      change.

PMID- 14671788
TI  - Chemical modification of mammalian cell surfaces.
AB  - The mammalian cell surface is a highly heterogeneous chemical environment with
      proteins, carbohydrates, lipids and composite molecules controlling vital cell
      functions. Chemical modification of this environment is a challenge due to the
      complexity of the surface chemistry and the fragility of the cell. Here, we
      review recent attempts to perform targeted, non-genetically controlled, changes
      to cell surface chemistry. Potential applications of cell surface engineering are
      presented.

PMID- 14671789
TI  - From transcription factors to designed sequence-specific DNA-binding peptides.
AB  - Transcription factors are DNA-binding proteins responsible for initiating the
      transcription of particular genes upon interacting with specific DNA sequences
      located at their promoter or enhancer regions. The DNA recognition process, which
      is extremely selective, is mediated by non-covalent interactions between
      appropriately arranged structural motifs of the protein and exposed surfaces of
      the DNA bases and backbone. The great variability in DNA recognition by
      transcription factors has hampered the characterization of an amino acid-base
      step recognition code, making it very difficult to design non-natural peptides
      that can mimic the DNA-binding properties of these naturally occurring
      counterparts. However, in recent years, several transcription factor-based
      miniature proteins capable of tight interaction with specific DNA sites have been
      successfully constructed, most of them using bottom-up synthetic approaches.

PMID- 14671790
TI  - Theoretical methods for the simulation of nucleic acids.
AB  - Different theoretical methods for the description of nucleic acid structures are
      reviewed. Firstly, we introduce the concept of classical force-field in the
      context of nucleic acid structures, discussing their accuracy. We then examine
      theoretical approaches to the description of nucleic acids based on: i) a rigid
      or quasi-rigid description of the molecule, ii) molecular mechanics optimization,
      and iii) molecular dynamics. Special emphasis is made ion current state of the
      art molecular dynamics simulations of nucleic acids structures.

PMID- 14671791
TI  - NMR-based methods and strategies for drug discovery.
AB  - Nuclear Magnetic Resonance (NMR) spectroscopy has long been a favourite tool of
      chemists interested in host-guest systems because it permits access to a wealth
      of information about the molecular recognition reaction. NMR has evolved
      dramatically in the last 15 years and, in parallel with the development of NMR
      methods for the determination of protein structure, a variety of tools aimed at
      detecting protein ligand interactions have been proposed and are being now used
      both in industrial and academic laboratories as valuable tools for structure
      based drug discovery. Very recent developments have considerably increased the
      fraction of therapeutic targets that can be tackled by NMR and significantly
      reduced the amount of sample required for analysis; in this tutorial review we
      outline the essential NMR-based techniques and describe some examples of their
      implementation as part of drug discovery programmes.

PMID- 14671792
TI  - Recent developments in chiral anion mediated asymmetric chemistry.
AB  - Chemical reactions and processes often involve cationic prostereogenic or racemic
      reagents, intermediates or products. To afford instead non-racemic or enantiopure
      compounds, an asymmetric ion pairing of the cations with chiral anionic
      counterions can be considered. This review presents recent examples of the
      synthesis and use of chiral anions for stereoselective purposes.

PMID- 14671793
TI  - The multifarious world of transition metal hydrides.
AB  - Transition metal (TM) hydrides display a remarkable range of bonding types,
      encompassing classical M-H moieties, dihydrogen complexes containing the eta 2-H2
      ligand, and trihydrides which display quantum mechanical site exchange.
      Furthermore, C-H, Si-H and B-H moieties can bind to TM centres in an eta 2
      manner, to give sigma-bond complexes with a spectrum of M...H contributions. In
      addition to these primary bonding modes, TM complexes also indulge in a wide
      spectrum of hydrogen-bonding interactions, including both M...H-X and the unique
      type M-H...H-X. This review begins with a historical perspective of the
      development of TM hydride chemistry, and proceeds to focus on three significant
      developments of the past two decades: the discovery of sigma-bond and dihydrogen
      complexes, the involvement of TM hydrides in hydrogen bonding, and the role
      played by quantum mechanical phenomena in the chemistry and dynamics of TM
      hydrides. The account concludes with an overview of the inter-relationship
      between these apparently disparate novel aspects of TM hydride chemistry.

PMID- 14671794
TI  - [Distributions of haplotypes for three Y-STR loci in a Tibetan ethnic group of
      Chinese population by using Y-STR multiplexes].
AB  - OBJECTIVE: One multiplex genotyping system was developed in using silver staining
      with allelic ladders for three Y-chromosome STR markers (DYS434, DYS443, and
      DYS456), with a view towards the application of rapid and simple genotyping assay
      methods for DNA profiling. The distributions of haplotypes for three Y-STR
      loci(DYS434, DYS443, and DYS456) was investigated in a Tibetan ethnic group of
      Chinese population. METHODS: Allele and haplotype frequencies at these Y-STRs
      loci(DYS434, DYS443, and DYS456) were analysed by PCR amplification using Y-STR
      multiplexes, followed by horizontal non-denaturing polyacrylamide gelelec
      trophoresis in 101 unrelated males of Tibetan ethnic group in Lasa of China.
      RESULTS: A total of 31 different haplotypes were found, 16 of them being unique.
      The haplotype diversity value (which is the same as the discrimination index)
      calculated from all three loci combined was 0.9481, which is informative.
      CONCLUSION: The Y-STR multiplexes provide useful information for forensic
      analysis and paternity tests and can also be of great benefit for providing
      information not normally available from autosomal DNA systems.

PMID- 14671795
TI  - [Seven Y-specific loci haplotypes and their usefulness in forensic casework].
AB  - OBJECTIVE: To study genetic polymorphism of 7 Y-specific short tandem repeats
      (STR) and assess their usefulness in forensic casework. METHODS: 7 Y-STR have
      been amplified in two multiplex reactions, (Multiplex I:DYS391, GATA-A4, GATA-A10
      and GATA-H4. Multiplex II:DYS439,DYS437 and DYS434). PCR products were separated
      by polyacrylamide gels electrophoresis followed by silver stain. RESULTS: When
      372 unrelated individuals from the Han population in Guangdong were detected by
      those system, DYS391, GATA-A4, GATA-A10, GATA-H4,DYS439,DYS437 and DYS434 showed
      5,7,6,5,6,4,4 alleles, respectively. A total of 254 different haplotypes were
      identified, of which 201 (79.13%) were found in single individuals. The overall
      haplotypes diversity reached 0.9960. CONCLUSION: The 7 Y-STR loci are highly
      genetic polymorphism and they will be very powerful for establishing Y-STR
      database, understanding human origin, paternity testing and personal
      identification.

PMID- 14671796
TI  - [DNA analysis of a 500 year mummy sample].
AB  - OBJECTIVE: To accumulate experience for dated forensic matter analysis, for
      example, Mummy. METHODS: DNA are extracted by methods of phenol-chloroform and
      are purified by Wizard DNA clean-up system. The STRs locus are ampolification
      with Promega Powerplus 16 system. The mtDNA hypervariable region 1 (HV1) is
      amplificated by '3 pair primers'. The products were sequenced with 377 DNA
      sequencer. RESULTS: The STRs locus very distinctness and mtDNA sequence is
      correct. CONCLUSION: It is a valuable method for special forensic matters.

PMID- 14671797
TI  - [Study on the dynamic changing profiles of telomeric restricted fragment length
      among sex balanced different age groups].
AB  - OBJECTIVE: In human, both in vivo and in vitro, telomere shortening appears to be
      a major component of cell senescence and aging. The detailed telomere shortening
      status and mechanism in peripheral blood cell is needed to be further
      characterized. METHODS: One hundred and twenty three peripheral blood samples
      were collected from healthy individuals of different age groups and the mean
      telomeric restricted fragment (TRF) was measured using Southern Blotting with Dig
      labeled probe. The samples of different groups were homogenized in sex components
      as indicated by chi 2 test of sex ratio of different test groups (P > 0.05).
      RESULTS: The average length of TRF is shortening with aging and distinguished
      shortening dynamic profiles could be observed. Further analysis showed that there
      might be a shortening peak near the age of 5. CONCLUSION: There are distinguished
      dynamics profiles of telomere shortening among different age groups. Thus, the
      results indicate that it might be possible to infer individual age by telomeric
      restricted fragment length assay.

PMID- 14671798
TI  - [Genetic studies of 15 STR loci in Guangxi Miao population].
AB  - OBJECTIVE: The study was carried out to investigate genetic polymorphism of 15
      STR loci in Guangxi Miao population. METHORDS: DNA samples from southern China
      274 Miao unrelated individuals were screened by using AmpFlSTR Identifiler PCR
      Amplification Kit and 3100 Genetic Analyzer. RESULTS: These 15 loci meet the
      Hardy-Weinberg expectations. The matching probability of the 15 STR loci was 5.04
      x 10(-17), and combined paternity of exclution was 0.9999993 in Guangxi Miao
      population. CONCLUSION: Our results showed Identifiler PCR Amplification systems
      of 15 STR loci were useful enough to forensic case work in Guangxi Miao
      population.

PMID- 14671799
TI  - [The expression of Bcl-2 protein on acute myocardial ischemia/reperfusion and the
      significance in forensic pathology].
AB  - OBJECTIVE: To search the objective morphologic evidence for the forensic
      pathological diagnosis on the acute myocardial ischemia/reperfusion. METHODS: The
      expression of Bcl-2 protein in the early stage of acute myocardial
      ischemia/reperfusion(I/R) in rats were studyed with immunohistochemistry.
      RESULTS: There was no expression of Bcl-2 protein in control group. The
      expression of Bcl-2 protein began to increase in myocytes 0.5 h after I/R in the
      ischemic areas and the expression of Bcl-2 protein in inner layer was stronger
      than in outer layer. The expression of Bcl-2 protein appears firstly in the inner
      layer of myocardium and extended gradually toward the outer layer 1 h after I/R.
      It was found that the expression of Bcl-2 protein in outer layer was stronger
      than in inner layer, then the expression of Bcl-2 protein became weaken
      gradually. CONCLUSION: Bcl-2 gene may be an important regulative gene in the
      process of apoptosis and the changes observed in this paper might be useful for
      the forensic pathological diagnosis on the early myocardial ischemia.

PMID- 14671800
TI  - [Identification of limited capacity for duties in schizophrenia: review of 31
      cases].
AB  - OBJECTIVE: To study general rule existed in identification of limited capacity
      for duties in schizophrenia and put forward some recommendations to the related
      issues. METHODS: The data of 31 cases were analyzed based on essential items in
      identification of limited capacity for duties in Schizophrenia in order to obtain
      the contribution rate of major variables. RESULTS: It showed that the
      contribution rate of from variable 1 to variable 6 was 18.785%, 15.549%, 14.023%,
      10.347%, 9.437% and 7.923% respectively, in which the variable 1 reflecting
      patient's recognition of dangerous act was the most important of all variables.
      CONCLUSION: The limited capacity for duties in Schizophrenia could be divided
      into three grades.

PMID- 14671801
TI  - [Determination of the hemoglobin in poisoned blood by spectrophotometery].
AB  - OBJECTIVE: In order to establish a objective method of analysis in the case of
      sulfured hydrogen poison. METHODS: The sulfured hemoglobin of the
      biomaterials(blood) were investigated by the spectrophotometry. RESULTS: Results
      showed that sulfured hemoglobin had a specific absorbance peak at 612 nm, it is a
      linear relationship about the absorbancity to the concentration of sulfured
      hemoglobin. CONCLUSION: It is possible to mark the poison degree by the
      spectrophotometery.

PMID- 14671802
TI  - [Advances of study on the formulae based on a correlation and linear regression
      between the potassium concentration in the vitreous humor and the post-mortem
      interval and the factors which modifies the relationship].
AB  - In this paper we reviewed the formulae and analyzed the factors which modified
      the relationship and estimate the time of death as precise as possible by
      potassium concentration in vitreous humor. The extra factors including numbers of
      the cases, cause of death, different eye of both, the urea or/and creatinine in
      vitreous humor, environmental temperature, sampling techniques, experimental and
      analytical method were also mentioned.

PMID- 14671803
TI  - [Cardiac troponin T and I: application in myocardial injury and forensic
      medicine].
AB  - The Cardiac Troponin T and I are highly cardiac specific biochemical markers of
      myocardial injury. They are very sensitive markers to detect all kinds of
      myocardial injury, and are able to distinguish myocardial injury and skeletal
      injury. Furthermore, They are independent predictor of future cardiac events.
      Such markers are now widely used in the clinic practice. It is prospective to use
      them in Forensic Medical Science.

PMID- 14671804
TI  - [DNA-based technique and species identification].
AB  - The species identification plays a key role in forensic analysis. Generally,
      three methods have been applied for this purpose, they are morphologic-based,
      serologic-based and DNA-based techniques. This review mainly discussed the DNA
      based technique and evaluate it's value in species identification of forensic
      science.

PMID- 14671805
TI  - [Proceeding of research on X chromosome genetic markers].
AB  - The development of Human Genome Project (HGP) makes it possible and more
      important to reveal the variations or polymorphisms precisely between different
      individuals and populations. Due to the characters of their high polymorphism and
      value in disease-linkage analysis as well as pharmacogenomnics, genetic markers
      on X chromosome have attracted much more attention of current medical and
      forensic scientists. This report summarized the proceeding of research on X
      chromosome genetic markers in the clinical and forensic context.

PMID- 14671806
TI  - [Geriatric pharmacology].

PMID- 14671807
TI  - [Psychopharmacotherapy in advanced age].
AB  - In recent years, psychopharmacotherapy in the elderly has been advanced by the
      introduction of newly developed drugs with high effectiveness and good
      tolerability. However, up to now these advances have not yet led to a broad
      change in the psychopharmacological treatment of elderly patients. Elderly
      patients with psychiatric disorders are frequently treated with older drugs,
      which have a high risk of side effects and drug interactions. The consequences
      are severe complications, such as falls or delirious episodes. In this article,
      general aspects of psychopharmacotherapy in the elderly will be briefly
      summarized. Special aspects of the treatment with antidepressants,
      antipsychotics, benzodiazepines, phase prophylactics and antidementives will be
      discussed in detail and recommendations for treatment will be given.

PMID- 14671809
TI  - [Pharmacotherapy of rheumatic diseases in the aged].
AB  - The optimal drug therapy of inflammatory rheumatic diseases is based on an
      individual concept of treatment combining several antirheumatic drugs with
      different modes of acting. In treating older patients this individual concept has
      to consider special conditions, as these patients often receive further
      medications due to different indications so that pharmacologic interactions and
      comorbidity have to be taken into account. Recently, new substances like COX-2
      inhibitors, the new disease modifying antirheumatic drug (DMARD) Leflunomide and
      particularly the cytokine-blockers provide new and highly effective treatment
      options. The administration of these drugs in elderly patients is discussed.

PMID- 14671808
TI  - [Cardiovascular pharmacotherapy in the aged].
AB  - Prevalence of cardiovascular diseases increases with advancing age. Moreover,
      these patients are getting older and older. Therefore, pharmacotherapy of the
      elderly becomes a major objective in clinical cardiology. Pharmacodynamic and
      pharmacokinetic changes in the elderly can interfere with a sufficient treatment
      of cardiovascular diseases and moreover, multiple drug usage is a considerable
      risk factor of possible drug-drug interactions. Furthermore, treatment of
      cardiovascular diseases as hypertension, heart failure or coronary heart disease
      in the elderly according to the international guidelines is often limited due to
      co-morbidities restricting usage of the appropriate medication. This review
      addresses both, the treatment of cardiovascular diseases in the elderly and the
      pharmacological characteristics of frequently used drugs.

PMID- 14671810
TI  - [Pharmacotherapy of elderly patients from the clinical viewpoint].
AB  - Due to increasing incidence of chronic diseases with advancing age, drugs are
      predominantly prescribed to elderly patients. But there is a lack of data,
      representing this age group. As the aging organism shows various physiologic
      changes that may influence pharmacokinetic parameters, an individualized risk
      benefit-analysis is warranted. Moreover, functional limitations may bare
      additional risks of pharmacotherapy promoting adverse drug reactions. Frequent
      adverse drug reactions in the elderly are falls, delirium and anticholinergic
      symptoms. An assessment of potential hazards of pharmacotherapy is therefore
      essential. It should include physiologic parameters, in particular renal
      function, possible functional limitations and parameters of compliance.
      Furthermore a prudent clinical monitoring of drug therapy can limit adverse drug
      reactions and polypharmacotherapy due to a prescribing cascade.

PMID- 14671811
TI  - [Therapy of hyperlipoproteinemia in the elderly].
AB  - Atherosclerosis associated diseases are the major cause of mortality in men and
      women over 65 years. Although the epidemiological relationship between
      hypercholesterolemia and cardiovascular disease is less prominent in elderly than
      in younger patients, the results of numerous intervention trials show that risk
      reduction can also be achieved in elderly and old patients. The numbers needed to
      treat to prevent one cardiovascular event is usually lower in this age group
      because of the high absolute rate of events. Therefore, in secondary prevention
      settings these patients should be treated similar to younger patients, i.e. a LDL
      cholesterol below 100 mg/dl should be achieved. In hyper- or dyslipoproteinemic
      patients without evidence of clinical or subclinical atherosclerosis cholesterol
      lowering drugs should be used restrictively.

PMID- 14671812
TI  - [Oncologic pharmacotherapy of elderly patients].
AB  - Age is the major risk factor for the development of cancer. Difficulties in
      medical treatment of elderly patients with cancer may be due to age dependent
      changes in physiological organ function, which result in pharmacokinetical and
      pharmacodynamical changes. They also may be due to co-morbidities with the need
      of pharmacological therapy. The choice of adequate treatment protocols has to
      consider this age dependent changes in pharmacokinetics and the presence of co
      morbidities. Most of the data reporting results of medical oncological treatment
      in patients with cancer are collected in younger patients. Therefore, the present
      knowledge concerning medical oncological treatment of elderly patients with
      cancer is still limited.

PMID- 14671813
TI  - [Problems of pharmacotherapy of infections in the aged].
AB  - Infectious diseases play an important role in the elderly. Disease progression is
      often more severe, displaying a higher complication rate and causing increased
      mortality. Elderly patients suffer more frequently than younger under pneumonia,
      exacerbations of chronic bronchitis, urinary tract infections as well as skin and
      soft tissue infections. When starting empiric antibiotic therapy one should
      consider that the bacterial spectrum afflicting elderly patients may differ from
      that afflicting younger patients. In addition an increasing number of nosocomial
      and multiresistant pathogens is seen in elderly patients due to more frequent
      hospitalisation and living in nursing homes. Patient multimorbidity and multiple
      co-medications make awareness of important drug-interactions essential. The
      purpose of this article is to review the indications and side-effects of well
      tried and newer antibiotics with respect to patients age. Especially the newer
      antibiotics Ertapenem, Linezolid, Quinupristin/Dalfopristin and Telithromycin are
      discussed in detail.

PMID- 14671814
TI  - [Pulmonary diseases in the elderly. Problems of pharmacotherapy].
AB  - In asthma, inhaled corticosteroids (ICS) can be regarded as disease-modifying
      drugs. They represent the mainstay of pharmacotherapy of asthma. In elderly, ICS
      are currently underused. In chronic obstructive pulmonary disease (COPD), there
      is recent evidence to suggest that ICS may reduce the rate and severity of COPD
      exacerbations and may improve health-related quality of life. Particularly
      patients with moderate-to-severe COPD appear to benefit from ICS therapy. In both
      asthma and COPD, fixed combinations of ICS and long-acting beta 2-agonists may
      provide clinically meaningful benefits to patients and may represent a further
      therapeutic advantage.

PMID- 14671815
TI  - [Drug therapy of elderly patients from the viewpoint of the clinical
      pharmacologist].
AB  - Polypragmasy (polypharmacotherapy) is often due to the frequent incidence of
      multimorbidity among elderly patients. This may evoke unpredictable drug
      interactions, which often become a reason for hospitalization. Additional
      medications might be the consequence. Geriatric patients are often characterized
      by variant pharmacokinetic parameters. Individualized drug-therapy should take
      into consideration not only the patients' age, liver and kidney functions but
      also the individual variability of hepatic metabolization and drug-resorption in
      the intestine based on genetic polymorphisms. Summing up, it is very important to
      verify a consisting or a new drug-therapy concerning its risk-benefit ratio and
      if it is needed, to omit or change some of the medications.

PMID- 14671816
TI  - [Chronic myeloproliferative diseases. Diagnosis and therapy].
AB  - Chronic myeloproliferative disorders (CMPD) are neoplastic disorders of the
      hematopoietic stem cell. Four different entities are defined: chronic myeloid
      leukemia (CML), polycythemia vers, essential thrombocythaemia, and idiopathic
      myelofibrosis. In addition, overlapping entities within the CMPDs and between
      CMPDs and myelodysplastic syndrome have been described. Diagnostic measures are
      performed to classify the subtype exactly and to assess risk factors and
      prognosis. Cytogenetic and molecular analyses are mandatory for the
      characterization of the malignant clone. Hydroxyurea and interferon-alpha have
      proven effective in all CMPE. In CML, specific inhibition of the elevated ABL
      tyrosine kinase activity with imatinib is associated with high response rates.
      Allogeneic stem cell transplantation is the only curative treatment option for
      all entities. In CML, the decision-making analysis should be based on established
      scores. In BCR-ABL negative CMPDs an allogeneic stem cell transplantation should
      only be performed in patients with unfavorable prognosis.

PMID- 14671817
TI  - [HIV positive patient with pancytopenia and massive splenomegaly].
AB  - A 30-year-old homosexual man presented with anemia and a several months history
      of recurrent fever, night sweats and weakness. His travel history included
      several stays in mediterranean countries during the recent years. Abdominal
      ultrasound showed massive splenomegaly, hepatomegaly and abdominal
      lymphadenopathy. A bone marrow aspirate revealed the presence of numerous
      Leishmania amastigotes, and bone marrow culture and polymerase chain reaction
      were also positive for Leishmania. In this case report epidemiological,
      immunological, diagnostic and therapeutic aspects of HIV-Leishmania coinfection
      are discussed with special emphasis on the impact of liposomal amphotericin B and
      highly active antiretroviral therapy on the treatment of HIV-leishmania
      coinfection.

PMID- 14671818
TI  - [Pulmonary infiltrates with blood eosinophilia in a 62-year-old patient].
AB  - A 62-year-old woman was admitted because of chronic cough and bilateral
      infiltrates on chest roentgenogram. Additional history revealed that the patient
      had been taken diclofenac emulgel during the previous 10 years for arthrosis.
      Diagnostic bronchoscopy showed eosinophilic alveolitis. After ruling out
      infectious, parasitic or systemic diseases drug-induced eosinophilic pneumonia
      was diagnosed due to topical diclofenac therapy and subsequent percutaneous drug
      absorption. No previous case of eosinophilic pneumonia to topical diclofenac was
      discovered in our review of the literature. The diclofenac therapy was
      discontinued. Oral corticosteroid therapy cleared bilateral infiltrates on CT
      scan within seven days. Drug reactions are the most common cause of pulmonary
      infiltrates with blood eosinophilia and/or eosinophilic alveolitis and should be
      considered as a differential diagnosis.

PMID- 14671819
TI  - [Infection control in the hospital with reference to MRSA (methicillin resistant
      Staphylococcus aureus)].

PMID- 14671820
TI  - Open wide--I meant your pocketbook: repercussions of the dental exclusion to the
      Medicare act.
AB  - For many Americans, dental coverage is merely a matter of cosmetics, a pretty
      smile. But for the elderly, a dental condition can affect nutrition, health, and
      financial well-being. In her note, Amanda Schwob explores the dental exclusion to
      Medicare, a provision of great concern to the elderly. Ms. Schwob seeks to define
      the scope of the dental exclusion by means of the plain language of the Medicare
      statute, case law, and legislative history. This analysis reveals startling
      uncertainty in this area of law. Next, Ms. Schwob considers several proposals
      before Congress as well as state reimbursement policies. The note concludes with
      concrete suggestions to remedy the ambiguity surrounding Medicare's dental
      exclusion.

PMID- 14671821
TI  - Cryoglobulinaemia.
AB  - Cryoglobulins are proteins, usually immunoglobulins that precipitate at
      temperatures less than 37 degrees C and redissolve on rewarming.
      Cryoglobulinaemias are classified according to the type of immunoglobulins and
      are associated with a number of disorders including plasma cell dyscrasias,
      lymphoproliferative disorders, autoimmune diseases and hepatitis C. The exact
      pathogenesis of the condition is not known. The clinical manifestations are
      varied and are due to ischaemia of tissues caused by the occlusion of vessel
      lumen. This review discusses the clinical manifestations, the current hypotheses
      of pathogenesis, the role of hepatitis C and finally the possibilities of
      treatment of the disease.

PMID- 14671822
TI  - [Gender differences in cardiology].
AB  - Frequent reports of gender differences in cardiology prompted us to study the
      cardiological situation in Tyrol, Austria, from 1995 to 2000. Mortality
      statistics for heart deaths 1995: women 1008 (53.5%), men 875 (46.5%); 2000:
      women 1104 (58.2%), men 792 (41.8%). Coronary heart deaths 1995: women 572
      (50.0%), men 571 (50.0%); 2000: women 634 (54.4%), men 531 (45.6%). Angiograms
      1995: women 332 (33.9%), men 646 (66.1%); 2000: women 688 (32.5%), men 1429
      (67.5%). Bypass surgery 1995: women 54 (33.0%), men 156 (67.0%); 2000: women 42
      (27.5%), men 157 (72.5%). Heart deaths 1995-2000: women +9.5%, men -9.5%;
      coronary heart deaths 1995-2000: women +10.8%, men -7.0%. By (welcome) contrast,
      coronary angiograms 1995-2000: women +107.2%, men +121.2%. Bypass operations 1995
      2000: women -22.2%, men +0.6%. Life expectancy 1995-2000: women +0.6%, men +0.6%.
      Patient age at heart death 1995-2000: women +1.8%, men +2.5%. In aggregate, we
      see that for decades more women than men have died a heart death, but that
      cardiac mortalities remain a typically "male bastion" with persistent gender
      differences in access to clinical cardiology. The worsening trend for women begs
      for awareness programs and corresponding preventive measures.

PMID- 14671823
TI  - [Cardiovascular risk factor profiles and angiography results in young patients].
AB  - There is a clear correlation between the incidence of coronary artery disease and
      existing cardiovascular risk factors. Therefore, it is a matter of interest if
      there is an accumulation of risk factors in younger patients with premature
      coronary artery disease compared to those without. We evaluated 1708 consecutive
      patients who underwent coronary angiography at our institution between August
      2001 to February 2002; 85 symptomatic patients under the age of 46 were included
      in our analysis. In 46 patients (54.1%)--mean age 41.5 +/- 3.6 years--a coronary
      artery disease was documented, in 39 patients (45.9%)--mean age 39.9 +/- 5.6
      years (n.s.)--normal coronary arteries were shown at angiography. Regarding the
      cardiovascular risk factors in young patients with coronary artery disease
      compared to young patients without we found a family history of premature
      coronary artery disease in 54.5% versus 43.6% (n.s.), hypercholesterolemia in
      56.5% versus 53.8% (n.s.), LDL cholesterol of 138 +/- 40 mg/dl versus 123.3 +/-
      27 mg/dl (s.), HDL cholesterol of 39 +/- 9 mg/dl versus 45.6 +/- 12.6 mg/dl (s.),
      serum triglycerides of 194.6 +/- 114.9 mg/dl versus 162.1 +/- 98.4 mg/dl (n.s.),
      diabetes mellitus in 15.2% versus 10.3% (n.s.), hypertension in 45.7% versus
      46.4% (n.s.), body mass index > 24.9 kg/m2 in 67.4% versus 69.2% (n.s.),
      cigarette smoking in 54.6% versus 56.4% (n.s.). And finally, a minimum of two of
      those risk factors was found in 93.5% versus 87.2% (n.s.). Due to the high
      prevalence of cardiovascular risk factors in both groups it is impossible to
      reliably predict the incidence of coronary artery disease from those risk
      factors. This has to be considered while deciding about the indication for
      coronary angiography.

PMID- 14671824
TI  - Hemodynamically unstable pericardial effusion in the Intensive Cardiac Unit:
      prospective study.
AB  - The authors have conducted a prospective investigation on 15 patients with
      hemodynamically unstable pericardial effusion (main criteria: echocardiographic
      signs of various degrees of right ventricular diastolic collapse and clinical
      instability) hospitalized in the Intensive Cardiac Unit (1.97% of all patients)
      for one year and have compared the results with literature data. The causes of
      pericardial effusion were neoplasms, infections, rupture of heart of aorta and
      hypothyroidism. Investigation revealed the most frequent findings: symptoms
      (dyspnea, retrosternal pain, loading intolerance, nonproductive cough), clinical
      signs (soft heart sounds, changes in pulmonal findings, fever, jugular venous
      distention, tachycardia, arterial hypotension and hepatomegaly), laboratory
      changes (elevated erythrocyte sedimentation rate, leukocytosis), ECG changes (ST
      T abnormality, microvoltage, tachycardia) and chest X-rays changes (enlarged
      cardiac silhouette, pleural effusion). Echocardiography found an average width of
      pericardial effusion of 2.5 cm (+/- 1.2), frequently thickened pericardium and
      changes in heart motions. The most used drugs in therapy were indomethacin,
      antibiotics, analgesics and corticosteroids. In three patients
      pericardiocentesis, and in two pericardiectomy were performed. Two patients died,
      13 patients were discharged from the ICU with an improved health condition.
      Literature data on this condition are either lacking, or differ from the above
      findings.

PMID- 14671825
TI  - [Gastroduodenoscopy for screening of patients scheduled for oral anticoagulant
      therapy: incidence and age dependence for potentially bleeding pathologies].
AB  - This retrospective study was designed to shed light on the incidence and age
      dependence of potentially bleeding pathologies in the upper gastrointestinal
      tract of asymptomatic patients scheduled for oral anticoagulant therapy.
      Gastroduodenoscopy was routinely performed during screening studies. The
      incidence of abnormalities was compared with gastroscopy findings of patients
      with epigastric symptoms. Only pathologies likely to bleed were considered. These
      included gastric ulcers, duodenal ulcers, esophageal varices, esophagitis,
      erosions, malformations and hemorrhages. RESULTS: 18.23% of the patients (n =
      746) undergoing gastroscopy prior to scheduled oral anticoagulant therapy were
      found to present with abnormalities versus 18.44% of those with epigastric
      symptoms (n = 1,627). In the group scheduled for oral anticoagulant therapy, the
      rate of pathologies did not significantly increase with increasing age.
      CONCLUSIONS: The unexpectedly high incidence of potentially bleeding pathologies
      in asymptomatic patients scheduled for anti-coagulant therapy should prompt
      screening gastroduodenoscopies irrespective of the patients' age prior to
      instituting treatment.

PMID- 14671826
TI  - Gamma-hydroxybutyric acid in the treatment of alcohol withdrawal syndrome in
      patients admitted to hospital.
AB  - Gamma-hydroxybutyric acid is a gamma-aminobutyric acid analogue which can be
      found in the human brain and is believed to be a neurotransmitter in the central
      nervous system. In animal experiments as well as in humans gamma-hydroxybutyric
      acid has been shown to alleviate the symptoms of the alcohol withdrawal syndrome.
      299 patients, who were admitted to hospital for reasons primarily unrelated to
      their alcohol dependence, were treated with gamma-hydroxybutyric acid when
      symptoms of the alcohol withdrawal syndrome occurred. Gamma-hydroxybutyric acid
      was usually given at a daily dose of 50 mg/kg in 3 divided doses, the clinical
      course of the patients was followed for 7 days or until discharge from hospital.
      Patients were 214 men and 82 women aged 18-87 years. The reasons for admission to
      hospital were frequently internal diseases, neurological/psychiatric problems,
      trauma or surgery. At the start of gamma-hydroxybutyric acid treatment, tremor
      was present in 81% of patients, sweating in 76% and unrest in 92%. Symptoms
      occurred 1-72 hours after admission. The efficacy of gamma-hydroxybutyric acid to
      ameliorate or suppress the symptoms of the alcohol withdrawal syndrome was judged
      to be excellent in 57%, good in 34%, fair in 18%, insufficient in 3% of patients.
      Drug tolerance was judged to be excellent in 79%, good in 17%, fair in 2% and
      poor only in 1% of patients. Adverse events were rare and mild. It is concluded
      that gamma-hydroxybutyric acid is an attractive alternative to tranquilizers in
      the management of the alcohol withdrawal syndrome in hospital.

PMID- 14671827
TI  - Increasing diversity in radiologic technology.
AB  - Diversity is increasingly important in the radiologic technology workplace. For
      significant changes to occur in work force diversity, educators must first
      recruit and retain students from a wide variety of backgrounds. This article
      examines personality, race and gender as factors affecting career choice and how
      educators can use these factors to increase diversity in their programs. An
      overview of the ASRT's efforts to improve diversity within the profession is
      presented, along with suggestions for developing effective recruitment and
      retention plans to increase diversity.

PMID- 14671828
TI  - Biological, chemical and radiological terrorism.
AB  - After completing this overview of terrorism, readers should be able to: Describe
      the early signs and symptoms of a covert terrorist attack. Discuss the
      radiographic signs of exposure to bioterrorism agents. List likely chemical,
      biological and radiological agents of terrorism. Categorize biological agents of
      terror by their Centers for Disease Control (CDC) threat level. Explain the
      relevance of syndromic surveillance in terrorism preparedness.

PMID- 14671829
TI  - Alzheimer disease and other dementias.
AB  - This article offers an overview of Alzheimer disease (AD) and its differential
      diagnosis from other dementias. After completing it, readers will: Be familiar
      with the prevalence of AD and other dementias. Summarize the major causes of
      dementia. Understand the basic pathology of AD. Recognize the common cognitive
      and noncognitive symptoms of AD. Identify the risk factors for AD and methods to
      prevent the disease. Describe the evaluation and diagnosis of AD. Discuss the
      role of structural and functional imaging in dementia diagnosis. Know how
      physicians manage AD symptoms. Assimilate this knowledge for use in encounters
      with patients with Alzheimer disease.

PMID- 14671830
TI  - Observations on German radiology.

PMID- 14671831
TI  - Double densities.

PMID- 14671832
TI  - Nontraditional clinical experience.

PMID- 14671833
TI  - Teachers, students and Attila the Hun.

PMID- 14671834
TI  - Curing cancer vs causing cancer.

PMID- 14671835
TI  - Readers dispute hepatitis facts.

PMID- 14671836
TI  - Readers dispute hepatitis facts.

PMID- 14671838
TI  - [Stem cell research in Flanders: (im)possibilities and perspectives. Summaries of
      the lectures presented during the symposium of June 13, 2003, organized in the
      framework of "The Fernand Nedee Conferences"].

PMID- 14671837
TI  - Patient page. Uterine fibroid embolization.

PMID- 14671839
TI  - [Production of (human) embryonal stem cells (ESC) and possible applications in
      genetics].

PMID- 14671840
TI  - [Stem cell research: ethical aspects].

PMID- 14671841
TI  - [Stem cell research: ethical aspects].

PMID- 14671842
TI  - [Cardiovascular stem cell research in interactions between the university and
      industry].

PMID- 14671843
TI  - [Stem cell research in hematology].

PMID- 14671844
TI  - [Stem cell research in the study of diabetes].

PMID- 14671845
TI  - [Stem cells: applications in neurology].

PMID- 14671846
TI  - [Stem cell research: state of the art].

PMID- 14671847
TI  - Study of the pathogenesis of paralytic ileus in animal models of experimentally
      induced postoperative and septic ileus.
AB  - Paralytic ileus is defined as an inhibition of propulsive intestinal motility.
      Postoperative ileus is the most common type, however, also during sepsis and
      critical illness paralytic ileus is a common finding. The pathogenesis of
      paralytic ileus is still debated. It is believed to result from the activation of
      inhibitory neural reflex pathways and activation of inflammatory processes. It is
      generally accepted that postoperative ileus results from the activation of an
      inhibitory neural reflex pathway. In our rat model we showed that different
      degrees of nociceptive stimulation activate different reflex pathways: laparatomy
      activates an adrenergic inhibitory reflex pathway, whereas manipulation results
      in additional activation of inhibitory NANC neurons releasing NO and VIP as
      neurotransmitters. We also demonstrated that blockade of the afferent limb of the
      reflex pathway by peripheral kappa-opioid agonists or by non-steroidal anti
      inflammatory drugs ameliorated postoperative ileus. However, the use of
      prokinetics lead to disappointing results. In the murine septic model we
      demonstrated an important role for activation of inducible NO synthase in the
      endotoxin-induced delay in gastric emptying and small intestinal transit. We
      hypothesise that activation of the residential macrophages in the gut wall leads
      to the production of iNOS and other inflammatory mediators. These mediators will
      attract more inflammatory cells and influence smooth muscle contractility. Next,
      we provide evidence that production of iNOS results in the activation of guanylyl
      cyclase leading to the production of cGMP and smooth muscle relaxation. However,
      a parallel mechanism of action for NO via oxidative stress needs further
      investigation.

PMID- 14671848
TI  - The integrase of the human immunodeficiency virus as a novel target for the
      antiviral therapy of AIDS.
AB  - Integration of the proviral DNA is a crucial step in the life cycle of the human
      immunodeficiency virus (HIV). Basic understanding of the cell biology of HIV
      integration will help the development of new antiviral drugs to complement the
      currently used cocktails of reverse transcriptase and protease inhibitors. Our
      research team has made major advancement in the field of antiviral research in
      recent years. The scientific-technological achievements were possible by the
      collaboration of a group of researchers with complementary research expertise.
      The integrase team is headed by Myriam Witvrouw and Zeger Debyser. After a
      general overview we summarized our most relevant publications. In the
      perspectives we referred to the ongoing work.

PMID- 14671849
TI  - On performance improvement and organizational recovery.

PMID- 14671850
TI  - Improving continuity of care: success of a behavioral health program.
AB  - This article documents the quality improvement process implemented by HIP Health
      Plan of New York (HIP) for the behavioral health continuity-of-care measure,
      Follow-Up After Hospitalization for Mental Illness. This Health Plan Employer
      Data and Information Set (HEDIS) measure identifies the percentage of members who
      receive psychiatric follow-up care after their hospital discharge. Studies
      indicate that post-hospitalization psychiatric follow-up care is an effective
      method for reducing hospital readmissions. HIP's mental health services
      department pursued a number of improvement initiatives with this HEDIS measure.
      The development of a case management unit proved the most effective intervention
      as compliance rates for post-hospitalization after-care visits improved and
      hospital readmittance rates declined. These findings provide valuable resource
      information for behavioral health providers throughout the United States.

PMID- 14671851
TI  - Setting up QI programs for pediatric specialty clinics.
AB  - This article reviews how to create a quality improvement (QI) reporting system
      for a multiple subspecialty pediatric clinic that is part of an acute pediatric
      facility in a major metropolitan area. The history of the facility, the needs of
      the organization, and areas that could be developed to create a comprehensive QI
      program are described. Examples of the data and format of QI studies are
      presented as well as future plans for continuing program development.

PMID- 14671853
TI  - Sam Ho on health system quality and population medicine. Interview by Nancy
      Houyoux.
AB  - As PacifiCare Health Systems' senior vice president and chief medical officer,
      Dr. Sam Ho is responsible for developing and implementing strategies and programs
      to improve the quality and cost-effectiveness of healthcare services throughout
      the company. Dr. Ho is responsible for all initiatives related to quality
      assessment and improvement, medical management, disease management, informatics,
      report cards, clinical product development, e-health, and healthcare liaison with
      public policy, government affairs, industry relations, media relations, provider
      network management, and sales and marketing. Since joining PacifiCare in its
      California MCO in October 1994, he has spearheaded companywide quality
      initiatives and improvement in population health outcomes, and developed the
      QUALITY INDEX profile of medical groups, a consumer-focused report card of
      provider performance. He also led efforts to achieve systemwide accreditation by
      the National Committee for Quality Assurance in all markets and Health Plan
      Employer Data and Information Set (HEDIS) score improvements. Previously he
      served as deputy director of health, medical director, and county health officer
      for the San Francisco Department of Public Health. He has held faculty
      appointments at the Schools of both Medicine and Nursing at the University of
      California, San Francisco. The Honolulu native received his BA in sociology from
      Northwestern University in 1972 with Phi Beta Kappa honors and his MD from Tufts
      University School of Medicine in 1976. Dr. Ho completed his residency in family
      practice at the University of California, San Francisco, and has since maintained
      board certification with the American Board of Family Practice.

PMID- 14671852
TI  - Tracking and improving influenza immunization rates in a high-risk medicare
      beneficiary population.
AB  - Immunization rates for end stage renal disease (ESRD) patients were well below
      the 80% target set by Healthy People 2000 and Centers for Medicare and Medicaid
      Services. The authors sought to increase documentation of immunization status,
      and influenza immunization rates of these patients. A survey was distributed to
      dialysis facilities to determine immunization practices. Facilities were provided
      with an immunization toolbox and spreadsheets to document the immunization status
      of patients. A total of 102 facilities (53%) provided data for three collection
      periods (1999, 2000, and 2001). Immunization rates for each influenza season
      increased significantly from 62.1% and 61.4% in 1998-1999 to 80.3% and 80.0% in
      2000-2001 (Pennsylvania and Delaware respectively).

PMID- 14671854
TI  - Hospitals and the competitive edge: how educated boards make a difference.
AB  - Hospital leaders face challenges from many different arenas--business, finance,
      and patient care. One resource often overlooked as a strategic asset is the
      hospital board of directors. Too often hospital boards erroneously assume or are
      forced into the roles of either micro-management or crisis management. Board
      education, which focuses on pertinent healthcare market information and strategic
      decision making, can help board members' understanding of their roles. As part of
      its overall plan, hospital leadership should ensure that its board members
      understand the market environment and its effect upon the hospital's strategic
      directions, options, and priorities. This article focuses on the structure and
      type of information that board members need to know to better guide the hospital
      leadership through the decision-making process and to fulfill their obligations
      to the institution they serve.

PMID- 14671855
TI  - A quality-driven physician compensation model: four-year follow-up study.
AB  - This case report describes a qualitative and preliminary quantitative assessment
      of a quality-based physician compensation program. The Hawaii Medical Service
      Association's Physician Quality and Service Recognition program offers an
      innovative and effective approach for improving delivery of high-quality and cost
      effective care to patients enrolled in preferred provider organizations. Support
      for the program is demonstrated through increasing numbers of voluntarily
      participating physicians. Preliminary assessment of population outcomes reveals
      sustained improvements in many clinical areas and mixed findings in others. This
      study contributes to the body of knowledge available to payers and policy makers
      considering alternative payment methods to reward improved performance.

PMID- 14671856
TI  - Second Annual Summit on Patient Safety & Information Technology.

PMID- 14671857
TI  - Must try harder.

PMID- 14671858
TI  - No butts.

PMID- 14671859
TI  - On reflection. Interview by Alastair McLellan.

PMID- 14671860
TI  - Clinical management. Where medicine meets management. Whose bright idea?
AB  - Managers can fall to act on creative thinking from the ground, often through
      preoccupation with the short term. Royal National Orthopaedic trust has pioneered
      voice-activated endosuites, CD-ROM training and cartilage transplants. Without an
      innovator, shaper and implementer, new projects are almost certain to fall.

PMID- 14671861
TI  - Curtain down on period drama.

PMID- 14671862
TI  - Older people. Shifting the balance.
AB  - Falls prevention pilots cut incidents by 60 per cent in three primary care
      trusts. Replication across the country would save 600,000 bed days a year. Pilots
      are expanding to eight PCTs and work is spreading to nutrition.

PMID- 14671864
TI  - HSJ people. Key to the door.

PMID- 14671863
TI  - Finance. Piggy in the middle.

PMID- 14671865
TI  - Pharma focus. Market traders.

PMID- 14671866
TI  - Pharma focus. Saints and sinners.

PMID- 14671868
TI  - Pharma focus. Blazing comet.

PMID- 14671867
TI  - Pharma focus. Puff adders.

PMID- 14671869
TI  - Pharma focus. Gene genies.

PMID- 14671870
TI  - Immunosuppression in renal transplantation: where are we now?

PMID- 14671871
TI  - NICE appraisals and cardiology: glycoprotein IIb/IIIa inhibitors and acute
      coronary syndromes.

PMID- 14671872
TI  - Chronic lung disease in infancy following prematurity.
AB  - Survival of extremely preterm infants has improved with modern neonatal intensive
      care. Chronic lung disease of prematurity, however, remains an important clinical
      problem and this article reviews the changing presentation and discusses new
      concepts of its aetiology.

PMID- 14671873
TI  - The role of infection in preterm labour and birth.
AB  - Preterm birth is the major cause of neonatal mortality and morbidity. Infection
      is a major cause of preterm labour. Abnormal genital tract flora in early
      pregnancy is predictive of preterm labour. Antibiotics may be of help in
      preventing preterm birth.

PMID- 14671874
TI  - The impact of multiple preterm births on the family.
AB  - As the number of multiple births has steadily risen over the past 20 years, twins
      and triplets form an increasingly large proportion of the preterm population.
      This causes a number of stresses to their families. Addressing the cause of the
      epidemic of iatrogenic multiple births is the most effective way to reduce the
      number of preterm infants and the long-term problems to which they are prone.

PMID- 14671875
TI  - Does trauma trigger multiple sclerosis? 2: A medicolegal view.
AB  - Set against the scientific debate in multiple sclerosis are a number of
      medicolegal cases in which the scientific evidence has been examined in the
      context of specific events. It is instructive to understand something of the
      legal approach to cause and association, and to consider this in relation to
      individual cases.

PMID- 14671876
TI  - Memantine (Ebixa) in the later stages of dementia.
AB  - Memantine is the first agent licensed for the treatment of moderate to severe
      Alzheimer's disease. It is an N-methyl D-aspartate (NMDA) receptor antagonist
      which reduces glutamatergic excitotoxicity. Benefits are seen in cognitive,
      functional and global measures in both outpatients and nursing home residents.
      Prospective health economic benefits have been reported.

PMID- 14671877
TI  - Atypical and conventional depot medications.
AB  - The introduction of atypical antipsychotics created a therapeutic dilemma between
      choosing the oral novel antipsychotic or the conventional depot form. Clinicians
      want the advantages of both, resulting in higher levels of polypharmacy. Modern
      psychiatry is probably in a transitional stage from the depot culture to safer
      oral medications or even to a safer depot culture.

PMID- 14671878
TI  - Who should stage upper gastrointestinal tract malignancy?
AB  - District general hospitals with trained upper gastrointestinal surgeons should
      undertake staging of patients with upper gastrointestinal cancers within their
      catchment areas. This could considerable reduce the workload at regional cancer
      centres.

PMID- 14671879
TI  - Management of stroke: acute, rehabilitation and long-term care.
AB  - Stroke is the major cause of disability in adults, resulting in much morbidity
      and mortality in the west. Each year 120,000 people will suffer their first
      stroke with a further 40,000 suffering a recurrent stroke and 40,000 a transient
      ischaemic attack. The prevalence rises from 2/1000 population to 2/100 in those
      over 85 years of age. Consequently stroke is seen as a problem of the elderly.

PMID- 14671880
TI  - The eye in diabetes.

PMID- 14671881
TI  - The role of human patient simulators in health-care training.
AB  - The use of human patient simulators in UK health-care training is increasing.
      These devices are educational tools for imparting knowledge, teaching technical
      skills, drill training and human factors training for single or multidisciplinary
      groups. This article explores some of the ways in which they are used,
      illustrated with examples of simulation training at Barts and the London Medical
      Simulation Centre.

PMID- 14671882
TI  - Spinal subdural haematoma after epidural anaesthesia: a diagnosis not to be
      missed.

PMID- 14671883
TI  - Coeliac disease and Crohn's disease: an association not to be forgotten.

PMID- 14671884
TI  - Relapsed non-Hodgkin's lymphoma with high CA-125 mimicking ovarian tumour.

PMID- 14671885
TI  - Evidence base on the orthopaedic NICE report.

PMID- 14671886
TI  - Lesser toe trauma is under reported.

PMID- 14671887
TI  - Should activated protein C be given to a patient who has an epidural?

PMID- 14671888
TI  - [Results of the medical support for the troops in the contra-terrorist operation
      of 1999-2002 in Northern Caucasus].

PMID- 14671889
TI  - [Theoretical aspects of thanatological analysis of casualties with lethal
      outcomes].

PMID- 14671890
TI  - [Surgical rehabilitation of the patients with gunshot injuries of small and large
      intestine].
AB  - The treatment experience obtained during the study of 87 patients with various
      forms of intestinal stomas after abdominal gunshot injuries has shown that the
      most favorable periods for restorative surgical treatment are 2-3 months in the
      patients with stoma closure performed as a local procedure, and 6 months in the
      patients with stoma closure with the use of laparotomy. The optimal methods of
      stoma formation, preoperative preparation including the treatment of paracostomal
      and inflammatory complications of the bowel, the development of methods to
      prevent the complications of the restorative anastomosis allowed to improve the
      treatment results.

PMID- 14671891
TI  - [The strength of fixation of mandibular bone fragments].

PMID- 14671892
TI  - [Modern approach to the therapy of gastroesophageal reflux disease].

PMID- 14671894
TI  - [Efficiency of "Vaxigrip" vaccine in the complex immunization of servicemen].

PMID- 14671893
TI  - [Principles of treatment and military medical examination of the patients with
      indolent Non-Hodgkin's lymphomas].
AB  - Non-Hodgkin's lymphomas (NHL) are the heterogeneous group of lymphoproliferative
      malignancies with distinct morphological, immuno-histochemical and genetic
      criteria of diagnosis, different character of clinical course, sensitivity to
      different treatment methods and disease prognosis. The WHO classification (1997)
      encompasses all the lymphoproliferative neoplasms. The NHL can be divided into 2
      prognostic groups: the indolent lymphomas and the aggressive non-Hodgkin's
      lymphomas. The indolent NHL types have a relatively favorable clinical prognosis,
      with median survival as long as 10 years, but they usually are not curable in
      advanced clinical stages. Early-stage (I and II) indolent NHL can be effectively
      treated with radiation therapy alone. In advanced stages of indolent NHL the
      chemotherapy is conducted.

PMID- 14671895
TI  - [Prophylaxis and treatment of herpes in women].

PMID- 14671896
TI  - [Applied significance of some morphological and functional parameters of health
      status in submariners].

PMID- 14671897
TI  - [Psychological basis for self-regulation of behavior in sailors drafted into
      military service].
AB  - Valuable-and-semantic spheres of Navy servicemen called-up for military service
      were investigated. For the servicemen with "psychical discomfort" the behavior
      "disadaptation" strategy is characteristic: the unrealistic orientation towards
      the freedom and material security; the problem of difficult choice between the
      interest in unofficial contact and the necessity to defer to rank; the "internal
      vacuum" state connected with little value of cognitive orientations and their
      relative accessibility, and on the contrary, the "internal conflict" state
      conditioned by the inaccessibility of vital and social values. The most of
      investigated persons are not oriented towards the highest levels of behavior self
      regulation that are connected with the search for sense and choice freedom. They
      are characterized by the regulation lowest levels connected with stereotype and
      comfort in observing the social standards (the group of "relative" psychical
      comfort) or by the non-adequate ways of behavior self-regulation that aggravate
      the disadaptation, morbidity and person's deformation (the group of "psychical
      discomfort").

PMID- 14671898
TI  - [The half-century anniversary of the department of physiology of underwater
      swimming in the Military Medical Academy].

PMID- 14671899
TI  - [To the history of Leningrad military medical school].

PMID- 14671900
TI  - [Modern state of the science of pain. Acute and chronic pain syndromes (report
      from 10th World Congress on Pain].

PMID- 14671901
TI  - [Perspectives of the direct search for analgesics: new "targets" (lecture)].
AB  - Essential distinctions in the neurophysiologic and neurochemical mechanisms
      related with the shaping of pain syndromes presuppose the administration of
      different-action analgetics in coping with such syndromes. Data, obtained
      recently in studying the fundamental mechanisms of nociception and analgesia,
      denote a variety of new "targets" for potential analgetics, i.e. cannabinoid
      receptors, NMDA-receptors of subtype NR2B, kainate and metabotropic receptors,
      central n-cholinergic receptors, vanilloid receptors and purinoceptors,
      tetrodotoxin-insensitive sodium channel SNS/PN3, calcium channels of N-type and
      gabapenti-binding protein.

PMID- 14671902
TI  - [Criteria for choosing the methods in pharmacotherapy of pain syndromes
      (lecture)].

PMID- 14671903
TI  - [The epidural administration of clofelin in experimental study].
AB  - The morphological and histoenzymological changes were analyzed in neurons of the
      bone marrow and spinal ganglia of outbred dogs after they were epidurally
      administered clonidine in acute (6.4 micrograms/kg) and chronic (15
      micrograms/kg) experiments. No pronounced structural-and-metabolic changes in the
      nervous tissue were revealed after clonidine administration. A certain
      morphological-and-functional realignment in the spinal nervous cells and ganglia
      is typical of both experimental animals and controls with a 0.9% sodium chloride
      solution being administered in the latter group within the chronic experiment.
      The registered shift did not exceed the limits of biological deviations, which
      most probably was indicative of the functional reaction in the studied nervous
      tissue structures to the epidural injections of drugs.

PMID- 14671904
TI  - [Manifestations of oxidative stress and its correction in traumatic shock].
AB  - The case study purpose was to investigate the oxidation-antioxidation process in
      the affected organism after traumatic shock and under the impact of Plapherone
      LB. A randomized experiment involved 94 patients who were shared between 2
      groups: group 1--routine intensive therapy, group 2--it received additionally
      Plapherone LB (sublingually, 2 mg protein/day). Ten persons of the control group
      were investigated separately. It was found by the method of electron paramagnet
      resonance that the antixidant system became weaker (in patients with traumatic
      chock), the lipoid oxidants got more intensified, the activity of their oxidant
      enzymes went up and the concentration of free radical got to be higher. Finally,
      Plapherone LB was found to promote the optimization of such systemic changes,
      since it normalized the xanthine oxidase activity in experimental traumatic
      shock.

PMID- 14671905
TI  - [Approaches to anesthesia management of a patient during oncological pulmonary
      surgery].
AB  - The results of lungs' excision in 82 patients made under a combined anesthesia of
      2 types are comparatively analyzed. A surface low-level endobronchial narcosis by
      isoflurane was administered in 42 patients concurrently with a "high" epidural
      anesthesia by bupivakain and fentanyl. The other 40 patients received isoflurane
      and intravenous bolus injections of fentanyl concurrently with epidural
      anesthesia by morphine administered at the lumbar level. The epidural analgesia
      by bupivakain and fentanyl made at the thoracal level or by morphine made at the
      lumbar level was carried on in the early postoperative period. The results show
      both variations to ensure a reliable intraoperative anesthesia, a smooth recovery
      and a good postoperative analgesia. Better results were on the whole obtained by
      the variant of high epidural anesthesia/analgesia; however, the method of lumbar
      morphine administration has a number of advantages primarily related with its
      simplicity.

PMID- 14671906
TI  - [Experience in the use of regional methods of anesthesia in oncological and
      gynecological surgeries].
AB  - The block loco-regional methods of anesthesia as applied to onco-gynecology
      surgery were used in 1310 patients with the predominant 2nd stage ASA risk. The
      best results (efficiency, safety, convenience) were ensured with spinal
      anesthesia by intraoperative sedative analgesia (micro-units of midazolam,
      propofol and ketamine) and by a 0.3 mg single-unit intramuscular injection of
      buprenorphine (made at the final surgery stage) that prevented a severe
      postoperative pain syndrome, which was later arrested by an "on-demand"
      intramuscular injection of peri pheral-action analgetics (ketoprofen or
      methamezol--therapeutic dose).

PMID- 14671907
TI  - [Variants of general anesthesia in surgeries for lymphoadenoid pharyngeal ring in
      children].

PMID- 14671908
TI  - [Pharmacological and physiological specificities of local anesthesia in
      dentistry].
AB  - Described in the paper are the specificity of local analgesia at the medical
      dental procedures and the effect produced by local anesthetics and
      vasoconstrictive agents on the induction of nervous fibers and peripheral blood
      circulation. The pharmacological-and-physiological mechanisms of local analgesia
      by a 2% artikain solution (with adrenalin, concentration 1:100,000) and by a 2%
      mepivakain solution (with adrenalin, concentration 1:100,000) exerted on the pain
      sensitivity and blood circulation in the tooth pulp are analyzed.

PMID- 14671909
TI  - [Safety of subarachnoid anesthesia during cesarean section in pregnant women with
      preeclampsia].
AB  - The paper contains data on a retrospective observation study of 54 cases of
      subarachnoid anesthetic management (SAM) for Cesarean section in pregnant women
      with preeclampsia. The results contradict the generally accepted viewpoint on
      that the SAM in patients with preeclampsia is not safe due to the negative
      methods impact on the hemodynamic state. No complications whatsoever were
      detected in mothers and fetuses of the experimental group, which was apparently
      due to a suggested set of preventive measures. The study confirmed the SAM safety
      in patients with preeclampsia.

PMID- 14671910
TI  - [The application of variational cardiointervalography for optimization of
      anesthesia in outpatient surgery].
AB  - The vegetative regulation condition was investigated by the method of variation
      cardio-interval-graphy in patients who underwent the intravenous anesthesia in
      the outpatient setting. The experience of using, on the differential basis, the
      sympathomimetic and vagotonic anesthetics for different-type vegetative tonus was
      analyzed. An optimal state in the vegetative regulation of the cardiovascular
      system, a stable hemodynamics and an adequate post-narcosis rehabilitation in the
      anesthetic management of one-day surgery were ensured owing to the suggested
      method in choosing an anesthetic.

PMID- 14671911
TI  - [Postoperative analgesia in abdominal surgery: a new look at an old problem].
AB  - Analgesia in abdominal surgery is a sufficiently complicated problem. The
      extensive surgeries in the abdominal cavity are concomitant with massive tissue
      damages and are associated the systematic tissue inflammatory response to an
      intensity of the pain syndrome and of other postoperative complications. The
      modern understanding of surgical-trauma pathophysiology is indicative of the
      necessity to modulate the systemic inflammatory response whose severity is
      preconditioned not only by postoperative pain intensity but also by surgical
      results. With respect to the above stated, multi-model analgesia can be regarded
      as an optimal technique since it presupposes the long-term administration of
      local anesthetics (preferably 0.2% ropivakain) concurrently with non-steroid anti
      inflammatory drugs used preoperatively (the most effective one is lornoxicam).

PMID- 14671913
TI  - [Clinical aspects of using patient-controlled analgesia with nonsteroidal anti
      inflammatory agents in postoperative period].
AB  - We used lornoxicam (n = 16) and ketorolac (n = 20) to study the possibilities of
      applying the non-steroid anti-inflammatory drugs within the postoperative patient
      controllable analgesia (PCA). With respect to a used analgetic, the frequency
      rate of good PCA anesthetic results was found, on day 1, to be 60-77%. The good
      anesthetic results were registered in 25% of patients when the routine scheme was
      in use. Non-steroid anti-inflammatory agents (lornoxicam, ketorolac) can be
      prescribed within the early postoperative PCA as basic analgetics, which
      essentially reduces the need in promedol without worsening the analgesia
      efficiency.

PMID- 14671912
TI  - [Selection of components and methods for postoperative analgesia after extensive
      abdominal surgeries].
AB  - The modern technique of postoperative analgesia after extensive and traumatic
      surgical interventions presupposes the administration, apart from opiates, a
      variety of preparations inhibiting the biological activity of substances
      (prostaglandins, kinins, TNF, leukotrienes, etc.), i.e. mediators of the systemic
      inflammatory response, which are of the key importance in modeling the
      postoperative pain. The paper deals with the specificity of postoperative
      analgesia at different stages of surgical treatment of patients with destructive
      pancreatitis (DP). The surgical tactics in DP envisages a primary revision of the
      abdominal cavity, necrectomy and omentobursostomy with subsequent multi ple stage
      based sanations of the abdominal cavity. The above surgical technique in DP is
      traumatic and long-lasting with the in-hospital treatment amounting on the
      average to 46.8 +/- 3.2 days. The entire postoperative period in DP patients is
      divided into 4 stages with each stage having a certain specific level of
      intoxication, systemic-inflammatory response and of pain syndrome. An analgesia
      scheme, based on epidural anesthesia combined with the inhibitors of kinin
      genesis (inhitril, contrical) of prostaglandin-genesis (ketorol of xefocam) and
      of a synthetic analogue of leu-enkephalines (daralgin). A specific combination of
      analgetics was typical of each treatment stage.

PMID- 14671914
TI  - [Analgesia after surgical procedures on organs of the abdominal cavity].

PMID- 14671915
TI  - [Continuous epidural infusion of ropivacaine hydrochloride (naropin) during
      postoperative analgesia in cardiosurgical patients].
AB  - An efficiency and safety of continuous infusion of naropin in the epidural
      analgesia of 38 patients after coronary artery bypass grafting were demonstrated.
      A variation of combined anesthesia, which was elaborated at the Russian Research
      Center of Surgery of the Russian Academy of Medical Sciences and which comprises
      (as a basic component of anesthetic management) a high thoracal epidural block
      (T2-T4) by continuous infusion of a 2% solution of naropin at a velocity of 5 +/-
      2 ml/h. Anesthesia was supported by isoflurane (0.5 +/- 0.9%). The patients were
      extubated in the operated theater and taken to the resuscitation unit with
      continuous infusion of 0.2% naropin solution. All studied parameters were
      registered after discharge from the operating theater and 1, 3, 6, and 16-18
      hours after surgery. The pain-syndrome intensity was measured at the verbal scale
      with 0 to 3 points. The mean duration of continuous naropin infusion was 16.7 +/-
      0.5 h, mean dose--2.2 +/- 0.2 ml/h. Naropin was administered at a dose of 1-3
      ml/h in 89.7% of cases and at a dose of 6 ml/h only in 2.9% of cases. The drug,
      when used in small doses, ensured a high anesthetic efficiency. A total lack of
      pain or a mild pain of 0.1 points was observed in 86.5% of patients at stage 5 of
      examinations and in 100% of patients at stage 3. Naropin infusion did not entail
      any impairment in ventilation or gaseous metabolism. A reliable decrease of
      arterial pressure (AP) and of central venous pressure (CVP), (p < 0.05) were
      registered beginning from stage 2. CVP decrease versus stage 1 was ensured in
      38.% of patients by stage 4 and the number of patients with a decreased CVP (less
      than 60 mm H) went up, versus stage 1, by 3 times. APsyst of less than 90-80 mm
      Hg was registered in 15 (39.8%) of patients at different examination stages,
      which necessitated the use of noradrenalin at mean dose of 174 +/- 21 ng/kg.min.
      The infusion of naropin at dose of 1-6 ml/h did not entail any impairment in the
      central nervous system (hallucinations, convulsions, and headache).

PMID- 14671916
TI  - [Methods and agents for prolonged analgesia in patients with spread forms of
      malignant neoplasms].

PMID- 14671917
TI  - [Arrest of the chronic pain syndrome using epidural analgesia in patients with
      disseminated prostate cancer].
AB  - Treatments results of 22 cases of atypical generalized and local carcinoma of the
      prostate involving different cells and tissues and accompanied by persistent
      neuropathic pain are described in the paper. The method of continuous epidural
      analgesia by an opioid agonist ((a 2% morphine hydrochloride solution and a local
      anesthetic) and by a 0.5% anekain solution provides for a smaller single dose of
      the preparation and for a less number of injections that should be used; it also
      eliminates the pain stress and improves the life quality of patients.

PMID- 14671918
TI  - [Effect of early enteral feeding on immune status in the immediate postoperative
      period].
AB  - The effect of the balanced feeding formulas "Peptamen" and "Nutren" ("Nestle
      Swisse", Switzerland) on the immune status was studied in 30 patients immediately
      after pancreas surgery. 15 patients with full-fledged parenteral alimentation
      were controls. The catabolic trend of metabolic processes was detected in the
      early postoperative period. The use of "Peptamen" and "Nutren" inverts metabolism
      towards anabolism. Profound immunologic disorders were observed both in the
      cellular and humoral chains immediately after surgery. The early enteral feeding
      normalized, first, the immunity humoral chain (from the 1st postoperative day)
      and, then, the immunity cellular chain (by the 6th postoperative day).

PMID- 14671919
TI  - [Program of hearing loss early detection in newborn infants in Cantabria. Results
      of the first year of activities].
AB  - AIMS: To report the findings in the first year of follow-up of the Cantabrian
      Program to screen newborn babies for congenital permanent hearing loss. METHODS:
      The study population consisted of infants born during a year period in Cantabria
      (Spain). Universal hearing screening by transient evoked otoacoustic emissions
      (TEOAE) in 2 stage protocol was performed. Infants with failure scores in these 2
      stages and those with risk factors for hearing loss were referred for diagnostic
      evaluation with auditory brainstem response. Hearing aids were recommended for
      those infants who had bilateral hearing loss and referrals to infant speech and
      language rehabilitation. RESULTS: Out of the 4117 eligible babies, 3987 were
      studied. One hundred and ten (2.6) had risk factors for hearing loss, 3.5% were
      referred for audiological assessment and 1.2/1000 were diagnosed as having a
      permanent hearing loss. The false-positive rate was 0.72% after the two-stage
      screening procedure was performed. Positive predictive value for permanent
      hearing loss was 10%. CONCLUSIONS: During the first year working with the
      Cantabrian Screening Program for congenital permanent hearing loss in newborn
      babies, the most part of the proposed aims have been achieved.

PMID- 14671920
TI  - [Use of topical ciprofloxacin in chronic suppurating otitis media].
AB  - OBJECTIVE: A prospective study is presented. We carry out an analysis of the
      results obtained after treatment with different protocols of administration of
      ciprofloxacin, during the active phase in chronic otitis media and in chronic
      otorrhea. MATERIAL AND METHOD: A multicenter, prospective study is carried out,
      in 3 ENT departments, corresponding to 3 reference tertiary hospitals. 300
      patients were included ranging from 5 to 73 years old, all were diagnosed of
      chronic disease of the middle ear: simple chronic otitis media (n = 128), chronic
      otitis with bone reabsorption (n = 57), cholesteatoma infection (n = 42) and
      postsurgery ear infection (n = 73). Patients were placed in 5 treatment groups:
      ciprofloxacin (oral administration) (only adults were included), topical
      ciprofloxacin (0.5%), topical ciprofloxacin (0.2%), topical ciprofloxacin (0.2%)
      plus oral ciprofloxacin and ciprofloxacin (0.3%) plus topical fluocinolone. There
      was a control group treated with polimixin plus neomicine and hidrocortison.
      RESULTS: The most common isolated bacterias were: Pseudomonas aeruginosa and S.
      aureus. We found 19 resistant strains to ciprofloxacin. A better therapeutic
      response was observed in the topical administration groups. In topical
      administration, a difference was only observed in the cholesteatoma and chronic
      middle ear infection with bone reabsorption groups, in those patients that were
      administered the ciprofloxacin with fluocinolone. CONCLUSION: Forms of topical
      treatment, with ciprofloxacin, in active infection of chronic disease of the
      middle ear, improve the results compared to oral administration. The association
      with of topical fluocinolone improves the results in the cases with cholesteatoma
      infection and chronic middle ear infection.

PMID- 14671921
TI  - [Pharyngeal globe and pharyngo-laryngeal reflux].
AB  - The globus sensation is one of the most frequent complaints in a basic ENT
      clinic. The etiology is still unknown, although some hypotheses have been
      suggested such as: psychological abnormalities, esophageal and cricopharyngeal
      muscle disfunction and the laryngopharyngeal reflux. Laryngopharyngeal reflux is
      the most frequent pathology related to the globus feeling. We've tried in this
      study to determine the incidence of laryngopharyngeal reflux in a group of 30
      patients with globus feeling. We found 26.7% of these patients with an abnormal
      pH monitoring test.

PMID- 14671922
TI  - [Treatment of laryngeal granuloma with anti-extraesophageal reflux medication].
AB  - OBJECTIVE: To asses the role of Gastroesophageal reflux in the genesis of
      laryngeal granulomas. PATIENTS AND METHODS: Prospective series of 7 patients
      diagnosed of posterior laryngeal granuloma, 5 were male, and 2 female, ages
      ranging between 46 and 65 years, (only three with symptoms of gastroesophageal
      reflux), who followed an antireflux protocol (recommendations, omeprazol 20 mg,
      cisapride 20 mg, almagato 4000 mg daily). RESULTS: All cases did well, showing
      complete healing of the larynx 60 days after the beginning of treatment.
      CONCLUSIONS: Gastroesophageal reflux is an important factor in the genesis of
      posterior laryngeal granulomas. It seems appropriate to start an antireflux
      regimen before surgery, which can be chosen for non responders or cases with
      severe respiratory symptoms, hoarseness, or for definitive diagnosis.

PMID- 14671923
TI  - [Detection of herpes simplex virus and Epstein-Barr virus in squamous cell
      carcinoma of the upper airways and digestive system].
AB  - OBJECTIVE: Previous studies have investigated the role of viruses in tumor origin
      of head and neck cancer. Despite this, mechanis of viral carcinogenesis remain
      unclear. The aim of this study is to determine the prevalence of herpes simplex
      virus (HSV) and Epstein-Barr virus (EBV) in malignant laryngeal and oropharyngeal
      lesions. MATERIAL AND METHODS: Fresh frozen specimens of 28 laryngeal and
      oropharyngeal squamous cell carcinomas were studied. The presence or absence of
      HSV and EBV was determined with polymerase chain reaction (PCR) assays. RESULTS:
      None of the samples showed evidence for EBV DNA. One tonsilar carcinoma case
      (3.5%) was positive for HSV DNA detection. CONCLUSIONS: These results do not
      support HSV and EBV as etiological factors in head and neck cancer.

PMID- 14671924
TI  - [Assessment of the prognostic capacity improvement of the 5th edition of the TNM
      in patients with nasopharyngeal carcinoma].
AB  - OBJECTIVE: Evaluate the changes included in the 5th edition of the TNM
      classification in patients with nasopharyngeal carcinoma. PATIENTS AND METHODS:
      Retrospective study of 103 patients with nasopharyngeal carcinoma treated with
      radical intention in our centre from 1985 to 1997. A reclassification according
      to the criteria defined in the 5th edition of the TNM was carried out. The loco
      regional control and survival obtained when patients were classified with the 4th
      and 5th editions of the TNM were compared. RESULTS: The use of the 5th edition of
      the TNM led to a decrease in local category (T) and stage grouping, improving the
      prognostic capacity in local control and survival. The changes included in the
      5th edition of the TNM did not modify the regional classification in a essential
      way. CONCLUSIONS: The changes included in the 5th edition of the TNM improved the
      classification of patients with nasopharyngeal carcinoma.

PMID- 14671925
TI  - [Hearing loss in Townes-Brocks syndrome].
AB  - In nineteen seventy two Towns and Brocks reported on a family in which the father
      and seven children showed anal atresia, triphalangeal thumb, metatarsal
      synostosis, extra fingers, neurosensorial deafness and ear abnormalities. The
      main traits were those related to hand, ear and anus alterations, transmitted
      under a dominant autosomal pattern. In this paper we present several members of
      the same family with similar alterations who finally were diagnosed of Townes
      Brocks syndrome.

PMID- 14671926
TI  - [Diagnosis and treatment of a case of benign paroxysmal posture vertigo of the
      horizontal canal].
AB  - Ahorizontal canal positional vertigo with apogeotropic and persistent directional
      changing nystagmus is reported. A new procedure consisting in cervical
      hiperflexion was used to determine the affected side in order to perform a
      particle repositioning manoeuvre.

PMID- 14671927
TI  - [Basilar artery aneurysm: report of a case].
AB  - We present a case of a patient with vertigo, disequilibrium and facial palsy.
      Nistagmus features pointed to a diagnosis of central vertigo. MRI showed a
      basilar aneurysm that compressed the brain stem and caused a stroke. We review
      the diagnosis.

PMID- 14671928
TI  - [Cystic fibrosis: relationship between genotype and phenotype].
AB  - Cystic fibrosis (CF) is one of the most common lethal autosomal recessive disease
      among the Caucasian population. It is caused by defects in the Cystic Fibrosis
      Transmembrane Conductance Regulator (CFTR) gene. More than 1000 different CF
      mutations have been described. This large heterogeneity of mutations could
      explain in part the great variability of clinical expression of the disease.
      However, the severity of the lung disease is very different among patients with
      similar CFTR genotype, even from the same family. These discrepancies in
      phenotypes within patients of the same genotype suggest the influence of
      nongenetic environmental factors and genetic modifiers outside the CF locus.

PMID- 14671929
TI  - [CFTR and transepithelial ionic transport abnormalities in cystic fibrosis].
AB  - The genetic disease cystic fibrosis (CF) is caused by mutations of the CF gene
      and generates defective Cl- transport across the affected epithelium. Recent
      progress have been made to understand CFTR activity and regulation in epithelia
      and its role in the muco-ciliary clearance of airway. This revue-overviews the
      mechanisms of transepithelial ion transport, the role of CFTR in that process and
      the consequences for CF of CFTR mutations.

PMID- 14671930
TI  - [Digestive symptoms in cystic fibrosis].
AB  - The prognosis of cystic fibrosis (CF) is strongly linked to the pulmonary status,
      nevertheless digestive disorders should be taken into account in order to prevent
      malnutrition which may increase pulmonary surinfections and speed up the
      deterioration of the respiratory function. Digestion, gut motility and absorption
      are the three major functions of the gastrointestinal tract. Functional disorders
      may involve the whole gut; in addition to pancreatic insufficiency we describe
      the failure of chloride secretion with dehydration of bowel content. Insufficient
      knowledge of the pathophysiology stresses the need for further studies to allow
      development of more rational and effective therapy.

PMID- 14671931
TI  - [Inflammation and cystic fibrosis].
AB  - Lung inflammation plays a pivotal role in the pathogenesis of airway disease in
      cystic fibrosis (CF). Inflammation occurs very early and can be identified in
      very young infants. Inflammatory response is also more intense in CF than in non
      CF airway inflammatory diseases. Among the different cell types involved in the
      airway inflammation, neutrophils are recognized to play a central role by
      releasing proinflammatory mediators, such as reactive oxygen species and
      proteolytic enzymes. Whether inflammation arises independently from infection
      remains debated. While infection was demonstrated to clearly amplify the
      inflammation, several studies argue for the possibility of an intrinsic
      inflammation. Finally, there is also evidence that the severity of pulmonary
      disease is linked to other genetic factors outside the CFTR gene locus, involved
      in host defence and inflammation.

PMID- 14671932
TI  - [Pathogenic bacteria in cystic fibrosis].
AB  - Since the CF gene identification in 1989 and despite the improvement of our
      knowledge in the physiopathology of the disease, bronchopulmonary infection
      determines the vital prognosis. Following Staphylococcus aureus infection,
      patients are colonized or colonized by Pseudomonas aeruginosa, greatly involved
      in the pulmonary deterioration. Other bacteria may be involved Burkholderia
      cepacia, Stenotrophomonas maltophilia, Alcaligenes sp. Intensive antibiotic
      treatment of primocolonisation helps to prevent or delay chronic colonisation.
      Chronic colonization needs a rational long term antibiotic strategy to prevent
      the occurrence of multiresistant germs; antibiotic cures are performed every 3 or
      4 months before pulmonary exacerbation symptoms.

PMID- 14671933
TI  - [Antibacterial therapy outside of Pseudomonas aeruginosa].
AB  - Hemophilus influenzae and Staphylococcus aureus (SA) are the predominant
      pathogens in infants with cystic fibrosis (CF). SA was the major cause of death
      in the pre-antibiotic era. The reason of the association of SA in CF is unclear.
      SA causes early damage of the respiratory tract and paves the way for Pseudomonas
      aeruginosa (PA). Based of this hypothesis, some centers use prophylactic
      antibiotics, but their efficacy is not proved and may favor growth of PA.
      Treatment of exacerbations is mandatory. Oral antibiotics are preferred in most
      cases, although few controlled clinical studies have been reported. Emergence of
      methicillin-resistant Staphylococcus aureus (MRSA) strains appeared during the
      recent years. Treatment of MRSA is difficult, patients segregation is discussed.

PMID- 14671934
TI  - [Antibiotic therapy against Pseudomonas aeruginosa and other gram-negative
      bacteria in cystic fibrosis].
AB  - In cystic fibrosis patients, bronchial infection with Pseudomonas aeruginosa (PA)
      is frequent, occurring often early in life. It becomes chronic because of a
      particular relationship between bacteria and host. Intensive antibiotic treatment
      often permits a transient eradication. When infection becomes chronic,
      antibiotics must be prescribed in a way to afford resistance. Efficacy of
      nebulized antibiotics is now recognized. Problems persist. Because of the
      difficulty to eradicate PA, new strategies may consist in diminishing the
      pathogenicity of PA, by inhibiting adhesion and virulence factors' production.

PMID- 14671935
TI  - [Inhaled bronchodilators and mucolytic agents in cystic fibrosis].
AB  - Poor clearance of airway secretions contributes to the pulmonary disease in
      cystic fibrosis (CF). Bronchodilator therapy might benefit in CF, but the
      efficacy is controversial. Effects of mucolytic agents have not been demonstrated
      conclusively. Only, efficacy of recombinant human deoxyribonuclease (rhDNase) is
      established with a rapid onset of benefit.

PMID- 14671936
TI  - [National neonatal screening program for cystic fibrosis: management and
      organization].
AB  - France has decided to add to the national neonatal screening program
      (Phenylketonuria, Hypothyroidism, Congenital Adrenal Hyperplasia, Sickle cell
      disease) the screening of cystic fibrosis (CF). The screening of CF will be
      implemented in all regions of France by the end of 2002 and will cover all
      newborn (near 800,000/year). Based on the recommendation of the French Screening
      Foundation, the project has been approved by the Health Ministry and will be
      financed by the social security. CF neonatal screening is now technically
      feasible and reliable. The proposed methodology includes: immunoreactive trypsin
      (IRT) dosage on all newborns at day 3 (by radioimmunology "Cis Bio" or
      immunofluorescence "Delfia") followed by genotype CFTR analysis if IRT level is
      above 60 micrograms/L. Screening for 29 mutations is planned. If genotype is
      negative, control of IRT at day 21 will be obtained. Several requirements are
      included in the program: a protocol of care for the newly diagnosed CF in a
      specialised CF center; information to all parents of newborns; results of CFTR
      genotype has to be given during a clinical visit, even if negative. This
      screening program should allow to screen 98% of the cystic fibrosis patients
      before the age of 1 month. In order to ensure perfect efficacy, the CF screening
      program will be evaluated and modified if necessary.

PMID- 14671937
TI  - [Anti-inflammatory therapy in cystic fibrosis].
AB  - Cystic fibrosis lung inflammation is early, sustained and severe and would
      justify an anti-inflammatory treatment. At present, the inhaled corticosteroid
      treatment did not give evidence of efficacy, contrary to the oral presentation,
      but at the cost of side effects. Azithromycin gives more encouraging results with
      a good tolerance. New molecules are in the process of validation.

PMID- 14671938
TI  - [Future prospects in the management of cystic fibrosis].
AB  - Basic and clinical research in cystic fibrosis have led to several new hypothesis
      to improve the management of the disease. The numerous tracks for new therapies
      may be explained by the lack of firm patho-physiological explanations for the
      disease and of knowledge of the best targets to get a significant improvement of
      the patients. After initial great hopes, there has been important limitations and
      slow down of gene therapy, imposing to go back to research programs on new
      vectors. New hopes have arisen with protein therapies, including chaperones
      molecules that can activate mutated CFTR proteins within the cells. New anti
      inflammatory therapies are developed, including proteases inhibitors. The
      prevention of airway colonisation with Pseudomonas aeruginosa is fundamental and
      could go through the development of specific vaccines, cellular therapies or
      molecules directly acting on the virulent factors of the bacteria.

PMID- 14671940
TI  - Want to know what site features would satisfy physicians? Just ask.

PMID- 14671939
TI  - PDAs will play an important role in clinical care, but their reach is still an
      unknown.

PMID- 14671941
TI  - Survey measures physician views on the effect of Web health information.

PMID- 14671942
TI  - Children's Health System moves to distributed authorship.

PMID- 14671943
TI  - Deborah M. Lee-Eddie, CHE, Sr. V.P.,  Operations, Catholic Health Initiatives,
      Denver, Colorado. Interview by Kyle L Grazier.

PMID- 14671944
TI  - Six steps to creating a personal career-decision framework.

PMID- 14671945
TI  - Market management: a concept worth exploring.

PMID- 14671946
TI  - An assessment tool for developing healthcare managerial skills and roles.
AB  - This article is based on a study to identify, and by doing so help develop, the
      skills and roles of senior-level healthcare managers related to the needs of the
      current healthcare environment. To classify these roles and skills, a qualitative
      study was conducted to examine the literature on forces in the healthcare
      environment and their impact on managers. Ten senior managers were interviewed,
      revealing six roles as the most crucial to their positions along with the skills
      necessary to perform those roles. A pilot study was conducted with these senior
      managers to produce a final assessment tool. This assessment tool helps managers
      to identify strengths and weaknesses, develop in deficient areas, and promote
      competence in all areas as demanded by the market and organization. This tool can
      be used by organizations in the recruitment process and in the training process.

PMID- 14671947
TI  - Integrating Six Sigma with total quality management: a case example for measuring
      medication errors.
AB  - Six Sigma is a new management philosophy that seeks a nonexistent error rate. It
      is ripe for healthcare because many healthcare processes require a near-zero
      tolerance for mistakes. For most organizations, establishing a Six Sigma program
      requires significant resources and produces considerable stress. However, in
      healthcare, management can piggyback Six Sigma onto current total quality
      management (TQM) efforts so that minimal disruption occurs in the organization.
      Six Sigma is an extension of the Failure Mode and Effects Analysis that is
      required by JCAHO; it can easily be integrated into existing quality management
      efforts. Integrating Six Sigma into the existing TQM program facilitates process
      improvement through detailed data analysis. A drilled-down approach to root-cause
      analysis greatly enhances the existing TQM approach. Using the Six Sigma metrics,
      internal project comparisons facilitate resource allocation while external
      project comparisons allow for benchmarking. Thus, the application of Six Sigma
      makes TQM efforts more successful. This article presents a framework for
      including Six Sigma in an organization's TQM plan while providing a concrete
      example using medication errors. Using the process defined in this article,
      healthcare executives can integrate Six Sigma into all of their TQM projects.

PMID- 14671949
TI  - A pragmatic approach to quality training.

PMID- 14671948
TI  - Effects of high-involvement work systems on employee satisfaction and service
      costs in veterans healthcare.
AB  - Two strong imperatives for healthcare managers are reducing costs of service and
      attracting and retaining highly dedicated and competent patient care and support
      employees. Is there a trade-off or are there organizational practices that can
      further both objectives at the same time? High-involvement work systems (HIWS)
      represent a holistic work design that includes interrelated core features such as
      involvement, empowerment, development, trust, openness, teamwork, and performance
      based rewards. HIWS have been linked to higher productivity, quality, employee
      and customer satisfaction, and market and financial performance in Fortune 1000
      firms. Apparently, few prior studies have looked at the impacts of this holistic
      design within the healthcare sector. This research found that HIWS were
      associated with both greater employee satisfaction and lower patient service
      costs in 146 Veterans Health Administration centers, indicating that such
      practices pay off in both humanistic and financial terms. This suggests that
      managers implementing HIWS will incur real expenses that are likely to be more
      than offset by more satisfied employees, less organizational turmoil, and lower
      service delivery costs, which, in this study, amounted to over $1.2 million in
      savings for an average VHA facility.

PMID- 14671950
TI  - [Consensus conference. Management of patients with cystic fibrosis. Monday the
      18th and Tuesday the 19th of November, 2002, Luxembourg Palace, Paris.
      Observation, nutrition, gastroenterology and metabolism. Text of the
      recommendations (long version)].

PMID- 14671951
TI  - [Cystic fibrosis, therapy and compliance].

PMID- 14671952
TI  - [Cystic fibrosis, observation and therapeutics].

PMID- 14671953
TI  - [Question 1. What is the influence of nutritional status on the progression of
      cystic fibrosis? Physiopathologic aspects of nutritional disorders in the course
      of cystic fibrosis].

PMID- 14671954
TI  - [Question 1. What is the influence of nutritional status on the progression of
      cystic fibrosis? Influence of nutritional state on the progression of cystic
      fibrosis: clinical and epidemiologic aspects].

PMID- 14671955
TI  - [Question 2. What strategy for maintaining optimal nutrition? How and when to
      evaluate nutritional state in children with cystic fibrosis?].

PMID- 14671956
TI  - [Question 2. What strategy for maintaining optimal nutrition? The means of
      nutritional therapeutic interventions in patients with cystic fibrosis].

PMID- 14671957
TI  - [Question 2. What strategies for maintaining optimal nutritional state in
      patients with cystic fibrosis? When and how to evaluate nutritional state at the
      means of therapeutic interventions?].

PMID- 14671958
TI  - [Question 2. What strategy for maintaining optimal nutritional state? Influence
      of nutritional state on the progression of cystic fibrosis: physiopathologic,
      epidemiologic and clinical aspects of nutrition disorders].

PMID- 14671959
TI  - [Question 3. What diagnostic procedures prior to abdominal pain in children with
      cystic fibrosis?].

PMID- 14671960
TI  - [Question 3. What diagnostic procedures prior to abdominal pain in the patient
      with cystic fibrosis?].

PMID- 14671961
TI  - [Question 4. What diagnostic and therapeutic strategies in glucose metabolism
      disorders in the course of cystic fibrosis? Diabetes and cystic fibrosis:
      physiopathology and diagnostic criteria for glucose metabolism disorders].

PMID- 14671962
TI  - [Question 4. What diagnostic and therapeutic strategies in glucose metabolism
      disorders in cystic fibrosis? Therapeutic strategy in glucose metabolism
      disorders on cystic fibrosis].

PMID- 14671963
TI  - [Question 4. Diagnostic and therapeutic strategies in glucose metabolism
      disorders in the course of cystic fibrosis].

PMID- 14671964
TI  - [Question 5. What management of hepatobiliary injury in the course of cystic
      fibrosis? Physiopathology and diagnostic criteria of hepatobiliary injury in the
      course of cystic fibrosis].

PMID- 14671965
TI  - [Question 5. What management in hepatobiliary injury in the course of cystic
      fibrosis? Specific therapeutic strategy of hepatobiliary injury in the course of
      cystic fibrosis].

PMID- 14671967
TI  - The clinical laboratory data warehouse. An overlooked diamond mine.

PMID- 14671966
TI  - [Question 5. What management for hepatobiliary injury in the course of cystic
      fibrosis?].

PMID- 14671968
TI  - Intestinal spirochetes. Organisms in search of a disease?

PMID- 14671969
TI  - Emerging cancer diagnostics. "On slide" or "off slide": that is the question.

PMID- 14671970
TI  - Colonic spirochetosis in children and adults.
AB  - We undertook a retrospective analysis of colonic spirochetosis in 14 cases:
      females, 3; males, 11; children, 4; adults, 10. Two men had HIV infections. All
      children and both HIV-infected men had abdominal complaints, diarrhea, or both.
      Most other adults underwent colonoscopy for polyp screening (n = 4) or follow-up
      of Crohn disease (n = 1) or had other indications (n = 2) or diarrhea (n = 1).
      Histologically, spirochetosis was identified in all parts of the colon and was
      not strongly associated with active inflammation, mucosal injury, or changes of
      chronicity. Genotype analysis of 13 cases showed that 11 resulted from
      Brachyspira aalborgi and 2 from Brachyspira pilosicoli infections. Only 2
      patients were treated specifically with antibiotics, with complete resolution of
      abdominal symptoms in 1 patient with follow-up. Follow-up biopsy result were
      available for 2 patients who did not receive treatment; one showed persistent
      spirochetosis, and the other was negative. Spirochetosis in this series had a
      male predominance, was generally caused by B aalborgi, and occurred in 2 distinct
      clinical settings: children who often have abdominal symptoms and adults who
      typically are asymptomatic. While treatment information remains limited,
      treatment can lead to resolution of symptoms in some cases.

PMID- 14671971
TI  - Development of an immunohistochemical assay for the detection of babesiosis in
      formalin-fixed, paraffin-embedded tissue samples.
AB  - The hemoparasite Babesia can cause life-threatening infections to neonates,
      elderly and immunocompromised people, and people who have undergone splenectomy.
      By using pooled hamster serum samples collected 21 days after infection with
      Babesia microti, we developed an immunohistochemical assay for formalin-fixed,
      paraffin-embedded tissue (FFPET) samples and blood smears. By use of the
      immunohistochemical assay, parasites were detected inside erythrocytes present in
      the heart, spleen, and liver of experimentally and naturally infected animals.
      FFPET samples from 2 fatal and 1 nonfatal human cases demonstrated
      immunohistochemical assay-positive parasites in circulating erythrocytes in
      various organs, including lymph nodes and spleen. In addition, air-dried blood
      smears from 4 patients showed positive immunohistochemical staining inside the
      erythrocytes. The immunohistochemical assay showed cross-reactivity against the
      Babesia WA-1 strain but did not react against Babesia bigemina or Plasmodium
      falciparum. The immunohistochemical assay for Babesia microti successfully
      detected parasites in human and animal FFPET samples and blood smears. This
      technique will be useful for the diagnosis of clinically suspected cases and for
      differentiating Babesia microti infection from malaria. Application of this
      technique to animal models will better define pathogenic mechanisms, including
      the possible recognition of exoerythrocytic tissue stages.

PMID- 14671972
TI  - Inaccuracy of certain commercial enzyme immunoassays in diagnosing genital
      infections with herpes simplex virus types 1 or 2.
AB  - Type-specific serologic results may be inaccurate if not based on glycoprotein G
      (gG). Commercial tests based on crude antigen (Zeus Scientific, Raritan, NJ;
      Wampole Laboratories, Cranbury, NJ; DiaSorin, Stillwater, MN) and one using gG-1
      and gG-2 (Focus Technologies, Cypress, CA) were compared with Western blot on
      serum samples from patients with culture-documented first symptomatic episodes of
      genital herpes simplex virus (HSV) type 1 (n = 17) or HSV-2 (n = 49) infection or
      recurrent genital episodes (HSV-1, 30; HSV-2, 49). Concordance with Western blot
      results was 56% for Zeus, 63% for Wampole, 52% to 54% for DiaSorin, and 83% for
      Focus. Sensitivity and specificity, respectively, for HSV-1 were 77% and 53%
      (Zeus), 91% and 35% (Wampole), 98% and 8% (DiaSorin), 94% and 70% (DiaSorin
      predominant antibody), and 83% and 90% (Focus); for HSV-2 they were 88% and 81%
      (Zeus), 92% and 83% (Wampole), 96% and 54% (DiaSorin), 38% and 98% (DiaSorin
      predominant antibody), and 98% and 96% (Focus). Type-specific serologic testing
      for HSV should be performed with gG-based tests for accurate diagnosis of
      symptomatic genital herpes.

PMID- 14671973
TI  - Intestinal intussusception associated with adenovirus infection in Mexican
      children.
AB  - Formalin-fixed intestinal tissue specimens from 12 Mexican pediatric patients
      with intussusception were examined for the presence of adenovirus. Four patients
      (33%) had detectable adenovirus antigen in epithelial cells as determined by
      using immunohistochemical analysis. Two of the patients with positive
      immunohistochemical results had antigens in dendritic and mononuclear
      inflammatory cells, and 3 patients had positive results for species C adenovirus
      by in situ hybridization using adenovirus species-specific probes (A-F). A real
      time polymerase chain reaction assay specific for species C (nonenteric)
      adenoviruses was used to confirm immunohistochemical results and to amplify
      adenovirus DNA for sequencing. A sequence similar to that for adenovirus serotype
      1 was found in 1 patient, serotype 2 in another, and serotype 6 in a third; in
      the fourth patient, the sequence was indeterminate between serotypes 2 and 6. The
      assays used in this study proved useful for the identification of species C
      adenoviruses in formalin-fixed specimens from Mexican pediatric patients with
      intussusception.

PMID- 14671974
TI  - Four-color flow cytometry identifies virtually all cytogenetically abnormal bone
      marrow samples in the workup of non-CML myeloproliferative disorders.
AB  - Because of the relative insensitivity of conventional cytogenetics for
      identifying abnormalities in the non-chronic myelogenous leukemia (CML)
      myeloproliferative disorders (MPDs), we directly compared the abilities of flow
      cytometry and cytogenetics to identify such cases. We retrospectively identified
      66 patients whose bone marrow samples were evaluated for abnormalities of myeloid
      antigen expression by 4-color flow cytometry as part of the workup to rule out a
      non-CML MPD. The patients all had concurrent cytogenetic evaluation of the marrow
      and no evidence of the t(9;22). Compared with a series of 12 normal bone marrow
      samples, 30 of 66 specimens demonstrated definitive flow cytometric
      abnormalities, while the other 36 cases had normal (21 cases) or indeterminate
      (15 cases) results, with the latter showing only mild antigenic alterations.
      Strikingly, clonal cytogenetic abnormalities were found in 11 (37%) of the 30
      cases with flow cytometric abnormalities, compared with no cytogenetic
      abnormalities among the 36 normal and indeterminate cases. The most common
      abnormal myeloid-associated antigens included HLA-DR, CD13, and CD33. In
      experienced laboratories, 4-color flow cytometry represents a useful method to
      help distinguish benign from neoplastic marrow in the workup of non-CML MPDs.

PMID- 14671975
TI  - Differential expression of T-bet, a T-box transcription factor required for Th1 T
      cell development, in peripheral T-cell lymphomas.
AB  - We studied T-bet expression in 91 cases of peripheral T-cell lymphoma (PTCL) by
      immunostaining and found expression in 42 cases (46%), including all 5
      lymphoepithelioid lymphoma cases and 12 (86%) of 14 angioimmunoblastic lymphoma
      cases, but only 9 (25%) of 36 anaplastic large cell lymphoma cases. Expression of
      T-bet in PTCL correlates with expression of other markers of Th1 T-cell
      differentiation, including CXCR3 (P < .0001), CD69 (P = .0013), LEF-1 (P =
      .0007), and OX40/CD134 (P = .005), and absence of expression of markers of Th2 T
      cell differentiation, including CD30 (P = .0001) and CXCR4 (P = .0144). Of 22
      cases of PTCL immunoreactive for all Th1-associated markers previously studied
      and nonreactive for Th2-associated markers, 20 (91%) were immunoreactive for T
      bet. Of 22 PTCL cases immunoreactive for Th2-associated markers studied and
      nonreactive for all Th1-associated markers studied, 4 (18%) were immunoreactive
      for T-bet. The remaining 47 PTCL cases (52%) exhibited incomplete or mixed
      staining for Th1- and Th2-associated markers, with 18 (38%) of 47 immunoreactive
      for T-bet. T-bet is a new marker that may contribute to the diagnosis and
      subtyping of PTCLs. T-bet expression in these neoplasms provides further support
      for a model of PTCL in which tumor subsets express markers of, and may be derived
      from, Th1- or Th2-committed T cells.

PMID- 14671976
TI  - Histologic and immunohistochemical study of bone marrow monocytic nodules in 21
      cases with myelodysplasia.
AB  - Previously, 4 cases of myelodysplastic syndrome were reported that had unusual,
      distinct monocytic nodules in bone marrow. The monocytic nodules, predominantly
      composed of monocytes with CD68+ immunostaining, had no or low expression of Ki
      67 and topoisomerase II alpha. The purpose of the present study was to further
      define the associated clinical diseases, histologic features, and
      immunohistochemical characteristics of 21 such cases. Relevant hematopathologic
      slides of all cases were reviewed, and extensive immunohistochemical staining was
      performed. Most patients (15/21 [71%]) had monocytosis in the bone marrow, and
      chronic myelomonocytic leukemia was the most commonly associated clinical
      disease. In 4 patients, the monocytic nodules also were present in lymph node,
      spleen, or skin. Immunohistochemical staining results for the monocytes in the
      nodules were similar to those for plasmacytoid monocytes. Our study established
      that monocytic nodules can be present in myelodysplastic syndromes,
      myeloproliferative diseases, and acute myeloid leukemia; verified the monocytic
      lineage; and revealed the low proliferative state of these cells.

PMID- 14671977
TI  - Spurious automated platelet count. Enumeration of yeast forms as platelets by the
      cell-DYN 4000.
AB  - We recently encountered a patient with thrombocytopenia secondary to multiple
      drug therapy, disseminated prostatic adenocarcinoma, and sepsis who had a sudden
      decrease in his platelet count as enumerated by the Cell-DYN 4000 hematology
      analyzer (Abbott Diagnostics, Santa Clara, CA). A manual platelet count performed
      thereafter was even lower. The etiology of the spurious platelet count was
      clarified when numerous yeast forms were observed on routine microscopy of the
      peripheral blood smear. Subsequently, these organisms were identified as Candida
      glabrata from a positive blood culture (BACTEC 9240, Becton Dickinson,
      Cockeysville, MD). To our knowledge, this is the first report of spurious
      enumeration of yeast forms as platelets in an automated hematology system. The
      principle underlying platelet enumeration by the Cell-DYN 4000 system and other
      hematology analyzers and the value of microscopy on peripheral smears with
      unexpected CBC count results are discussed.

PMID- 14671978
TI  - Real-time reverse transcription-polymerase chain reaction assay for GA733-2 mRNA
      in the detection of metastatic carcinoma cells in serous effusions.
AB  - Cytomorphologic and immunocytologic examination alone provide only limited
      sensitivity for the detection of metastatic carcinoma cells in many cases of
      serous effusions. The specificity of conventional reverse transcription
      polymerase chain reaction (RT-PCR) methods for detection of epithelial gene
      transcripts is low owing to the ectopic expression of many such genes in
      nonepithelial cells. For the detection of metastatic carcinoma cells, we describe
      a quantitative real-time RT-PCR assay for GA733-2 messenger RNA encoding an
      epithelial glycoprotein (EGP-2) that binds to the monoclonal antibody BerEP4.
      With serial dilutions of BerEP4-positive SK-BR-3 breast carcinoma cells, the RT
      PCR assay was able to detect 10 carcinoma cells in a background of 10(6) lymphoid
      cells compared with 10(2) to 10(3) carcinoma cells detectable by immunocytologic
      examination. We analyzed 51 serous effusions, including 25 malignant metastatic
      effusions, by the real-time RT-PCR assay. Receiver operating characteristic curve
      analyses demonstrated a sensitivity of 96% corresponding to a specificity of 98%
      for a correct diagnosis of metastatic effusions. These results provide evidence
      that the GA733-2 real-time RT-PCR assay is a specific and sensitive tool for the
      detection of metastasis of BerEP4-positive primary tumors in serous effusion
      specimens.

PMID- 14671979
TI  - Comparison of proliferation indices in glioblastoma multiforme by whole tissue
      section vs tissue microarray.
AB  - Tissue microarrays (TMAs) reduce the amount of tissue analyzed with the
      assumption that protein and gene expression patterns are homogeneous throughout
      tumors. Many tumor types, including glioblastoma multiforme (GBM), are
      heterogeneous in many regards, including cell proliferation. We retrospectively
      compared Ki-67 labeling indices (LIs) determined by whole tissue section (WTS) vs
      TMA in a series of 50 GBMs from 45 patients. A paired t test indicated that the
      difference between average LIs obtained from a TMA vs a WTS was not significant
      (P = .51). There was no correlation between TMA and WTS (r = 0.042; P = .77),
      indicating that the methods yielded very different results in individual tumors.
      The Ki-67 LI did not always correlate with the tissue section in an individual
      tumor; however, when evaluating a large number of tumors on a TMA, the LI range
      and mean LI were roughly comparable with the LI range and mean LI determined from
      the WTS.

PMID- 14671980
TI  - High-risk human papillomaviruses may have an important role in non-oral habits
      associated oral squamous cell carcinomas in Taiwan.
AB  - To evaluate the etiologic role of human papillomavirus (HPV) in oral
      carcinogenesis, DNA samples were purified from 103 oral squamous cell carcinoma
      (OSCC) and 30 normal oral mucosal (NOM) specimens. A nested polymerase chain
      reaction, DNA sequencing, and gene-chip HPV typing were used to identify multiple
      HPV types in our samples. We found that the positive rates of all HPV types and
      of high-risk HPV types were significantly higher in OSCC samples (49.5% and
      41.7%, respectively) than in NOM samples (6/30 [20%; P < .01] and 5/30 [17%; P <
      .05], respectively) and significantly higher in non-oral habits (OH)-associated
      OSCC samples (31/51 [61%] and 28/51 [55%], respectively) than in OH-associated
      OSCC samples (20/52 [38%; P < .05] and 15/52 [29%; P < .001], respectively). High
      risk HPV types and all HPV types had odds ratios of 3.97 (P = .0097) and 3.92 (P
      = .006), respectively. Our results suggest that HPVs, particularly high-risk
      HPVs, might be associated with the development of OSCCs, especially the non-OH
      associated OSCCs.

PMID- 14671981
TI  - Her-2/neu gene amplification in familial vs sporadic breast cancer. Impact on the
      behavior of the disease.
AB  - We compared the incidence of Her-2/neu amplification in patients with and without
      a family history of breast cancer and correlated gene status with clinicobiologic
      and prognostic features in sporadic and familial cases. Of 108 patients, 28.7%
      had gene amplification. Among 96 cases with family history information available,
      28 had an affected first-degree relative. The gene was amplified more frequently
      in familial than in sporadic cases (13/28 [46%] vs 14/68 [21%]; P = .01). Among
      familial cases, amplification was associated with adverse clinicobiologic
      features (poorly differentiated tumors [P = .05], larger tumors [P = .05], more
      lymph nodes involved [P = .04], and DNA aneuploid [P = .02] and highly
      proliferative tumors [P = .005]), and the relapse (P = .02) and disease-related
      death (P = .05) rates were higher than in cases without amplification. Among
      sporadic cases, amplification was not associated with significantly different
      disease features, except for a higher incidence of DNA aneuploid tumors (P =
      .01), percentage of S-phase tumor cells (P = .006), and lower proportion of
      estrogen (P = .001) and progesterone (P = .002) receptors. Her-2/neu
      amplification was observed more frequently among patients with a family history
      of breast cancer, in whom it was associated with adverse clinicobiologic features
      and a worse clinical outcome.

PMID- 14671982
TI  - Evaluation of an automated, latex-enhanced turbidimetric D-dimer test (advanced D
      dimer) and usefulness in the exclusion of acute thromboembolic disease.
AB  - Advanced D-dimer (Dade Behring, Marburg, Germany) is a latex-enhanced
      turbidimetric test for the quantitative determination of D-dimers. To evaluate
      this assay, examine test performance on 2 instruments (BCS Analyzer and Sysmex CA
      1500, Dade Behring), establish negative predictive value cutoffs (NPVCs), and
      compare the test with the qualitative SimpliRed test (Agen Biomedical, Brisbane,
      Australia), we evaluated 117 patients for possible acute thromboembolic disease
      (pulmonary embolus or deep venous thrombosis). Patients selected for the study
      were those with confirmatory tests (ultrasound, spiral computed tomography,
      ventilation-perfusion scan, or angiography) and those without certain medical
      conditions that might be associated with increased D-dimers. An NPVC of 1.8 mg/L
      for the BCS Analyzer resulted in 41.0% negative results (48/117) and sensitivity,
      specificity, and negative and positive predictive values of 100%, 48%, 100%, and
      21%, respectively. An NPVC of 1.1 mg/L for the Sysmex CA-1500 resulted in 31.6%
      negative results (37/117) and sensitivity, specificity, and negative and positive
      predictive values of 100%, 36%, 100%, and 18%, respectively. The SimpliRed had
      31.6% negative results (37/117) and sensitivity, specificity, and negative and
      positive predictive values of 86%, 34%, 96%, and 15%, respectively.

PMID- 14671983
TI  - Clinical pathology consultation improves coagulation factor utilization in
      hospitalized adults.
AB  - Coagulation factor replacement can effectively treat or prevent most hemophilia
      complications, but it is expensive. Although published data describe how to
      achieve therapeutic goals through cost-effective selection and dosing of
      replacement products, criteria are not universally known or followed. A review of
      our institution's experience revealed overdosing of coagulation factors in the
      majority of patients treated during a 12-month period, at a cost that approached
      $700,000. Consequently, we established mandatory clinical pathology consultation
      before releasing such factors. In the subsequent 30 months, 32 adults received 64
      courses of treatment. For patients with hemophilia A, the mean cost per admission
      was reduced by approximately 27% (total savings, $61,536). For patients with
      factor VIII inhibitor, there was an approximate 6% cost reduction (total savings,
      $47,292). The combined savings was $108,828. The mean plasma factor level
      achieved during the intervention period was 84% +/- 55% compared with 117% +/-
      58% for the preintervention period (P = .008). Neither the number of treatment
      (factor transfusion) days nor the number of RBC transfusions changed
      significantly. Our data support that pathology consultation yields consistent and
      appropriate therapy and improves resource utilization.

PMID- 14671984
TI  - A comparison between six- and four-week intervals in surveillance of oral
      anticoagulant treatment.
AB  - We determined whether international normalized ratio (INR) monitoring at 6 weeks
      rather than 4 weeks would benefit patients and reduce costs. Patients receiving
      stable oral anticoagulation treatment (target INR, 3.0) with a prosthetic
      mechanical heart valve for more than 6 months were randomized for a maximum
      interval between INR determinations of 6 weeks (group 1, n = 59) or 4 weeks
      (group 2 [control], n = 65). Patients were followed up for 2 years. The primary
      end point of the study was the biologic risk of overanticoagulation or
      underanticoagulation, estimated as the rate of values at risk (INR, < 1.5 and >
      5). The rates of INR values at risk for hemorrhagic (INR, > 5) or thromboembolic
      (INR, < 1.5) complications were 3.27% in group 1 and 3.09% in group 2 (P = .81).
      The INRs of patients in group 1 trended toward higher values, but no difference
      between groups was observed in time spent at various INR ranges by using the
      method of linear change. The mean time between INR determinations was 24.9 +/-
      18.1 days (1.20 per month) in group 1 and 22.5 +/- 9.5 days (1.33 per month) in
      group 2 (P < .0003). For patients in stable condition with a prosthetic heart
      valve who are monitored at an anticoagulation clinic, a 6-week interval between
      INR determinations does not increase the biologic risk of thromboembolic or
      hemorrhagic events.

PMID- 14671985
TI  - Introduction to the special issue on functional capacity evaluations: from expert
      based to evidence based.

PMID- 14671986
TI  - Test-retest reliability of the Isernhagen Work Systems Functional Capacity
      Evaluation in patients with chronic low back pain.
AB  - The aim of this study was to investigate test-retest reliability of the
      Isernhagen Work System Functional Capacity Evaluation (IWS FCE) in a sample of
      patients (n = 30) suffering from Chronic Low Back Pain (CLBP) and selected for
      rehabilitation treatment. The IWS FCE consists of 28 tests that reflect work
      related activities like lifting, carrying, bending, etc. In this study, a
      slightly modified IWS FCE was used. Patients were included in the study if they
      were still at work or were less than 1 year out of work because of CLBP.
      Participants' mean age was 40 years, the duration of low back pain ranged between
      5 and 10 years. Fifteen patients (50%) were out of work for a mean of 17 weeks,
      and they all received financial compensation. Two FCE sessions were held with a 2
      week interval in between. Means per session, 95% confidence intervals of the mean
      difference, one-way random Intra Class Correlations (ICC), limits of agreement,
      Cohen's kappa and percentage of absolute agreement were calculated where
      appropriate. An ICC of 0.75 or more, a kappa value of more than 0.60 and a
      percentage of absolute agreement of 80% were considered as an acceptable
      reliability. Tests of the IWC FCE were divided into tests with and tests without
      an acceptable test-retest reliability on the basis of the kappa values, the
      percentage of absolute agreement and the ICC values. Fifteen tests (79%) showed
      an acceptable test-retest reliability based on Kappa values and percentage of
      absolute agreement. Eleven tests (61%) showed an acceptable test-retest
      reliability based on ICC values.

PMID- 14671987
TI  - Reliability of upper extremity tests measured by the Ergos work simulator: a
      pilot study.
AB  - The objective of this paper was to assess the reliability of functional capacity
      evaluation (FCE) tests of the upper extremity in Ergos from three perspectives:
      human performance (in terms of a learning effect); order of the physical
      intensity (force) of the subtests (intensity effect); and performance in time
      (time of day effect). An experimental within-subjects design was performed.
      Twelve healthy males/females were tested in the morning or in the afternoon. The
      tests focused on sensibility, coordination, and strength of the upper extremity.
      A counterbalanced design was used for three orders of the three types of tests
      increasing in intensity. Each participant was tested three times over the course
      of 4 weeks. A learning effect was found in sensibility and coordination subtests.
      No order effect was observed in terms of the intensity of the subtests. A time
      effect was found in coordination tasks: keyboarding performance was better in the
      morning, and handling better in the afternoon. It was concluded that repeated
      upper extremity FCE testing in the present pilot study was found to be reliable
      over a 4-week period in healthy subjects.

PMID- 14671988
TI  - Development of a job-specific FCE protocol: the work demands of hospital nurses
      as an example.
AB  - Musculoskeletal disorders often result in employee disability leaves and sickness
      related absenteeism in the workplace. Professional evaluations of an employee's
      capacity to work require additional support by means of Functional Capacity
      Evaluation (FCE) methods. However, most FCE methods assess general physical
      capacity and, because of fixed test procedures, testing times range between 4 and
      6 h for up to several days. For return to work (vocational rehabilitation), the
      tests need to reflect the employees' specific work demands more precisely. This
      study aims to develop a job-specific FCE protocol on the Ergos Work Simulator for
      hospital nurses. In developing the contents of this specific protocol,
      hierarchical task analyses were performed with 20 nurses in four departments of a
      university medical center. A job-specific test protocol was developed that
      consisted of five steps. In this process, the original test protocol was analyzed
      first. Secondly, categorization of physical risk factors for work-related
      musculoskeletal disorders revealed 16 possible combinations of activity, posture,
      and load. Finally, duration and frequencies during one working day of these
      combinations were coupled to the Ergos test panels. The nurse-specific test
      protocol lasts 90 min. It was possible to develop a job-specific protocol, using
      on-site observations as the input. Compared to the original Ergos protocol, the
      external validity of the new job-specific protocol has improved: it simulates the
      functional capacity that nurses need to perform their job in a realistic way. The
      testing time of the original Ergos protocol is four times longer compared to the
      new job-specific protocol.

PMID- 14671989
TI  - Relationships between functional capacity measures and baseline psychological
      measures in chronic pain patients.
AB  - The extent to which baseline psychological measures, pain, and compensation
      status are related to admission and posttreatment functional capacity and
      employment outcome was investigated. Four pass/fail functional capacity tests
      based on the DOT (Dictionary of Occupational Titles) classification system and
      previously shown to be predictive of treatment outcome in chronic pain patients
      were analyzed in relation to baseline measures of depression, state and trait
      anxiety, and perceived stress. Statistical tests of all measures with employment
      level at admission to treatment, 1 month follow-up and at long-term follow-up
      were also performed. The results showed that pain level and/or compensation
      status were the primary predictors of functional capacity and employment status
      at follow-up. Admission functional capacity measures were also predictors of
      employment outcome. Depression scores at admission predicted some admission
      functional capacity results, however, psychological scores were not as
      significantly related to discharge functional capacity tests. One functional
      capacity test, the crouching test, was an independent predictor of short- and
      long-term employment outcome. Trait anxiety was the only psychological factor
      that was independently predictive of long-term employment outcome. In conclusion,
      these results suggest that psychological variables are related to measures of
      functional capacity measured at admission. However, psychological measures at
      admission are not good predictors of later functional capacity measures.
      Functional capacity measures are important predictors of follow-up employment
      outcome, but return to work cannot be predicted without taking pain into account.

PMID- 14671991
TI  - Relationship between kinesiophobia and performance in a functional capacity
      evaluation.
AB  - Fear of movement and (re)injury (kinesiophobia) has been postulated to play an
      important role in the performance in a Functional Capacity Evaluation (FCE). This
      study was performed to analyze the relationship between kinesiophobia and
      performance in an FCE. Kinesiophobia and FCE performance of 54 male and 10 female
      patients (mean age 38.0) suffering chronic low back pain (mean length of episode
      9.9 months, 93% off work) were assessed. Kinesiophobia was assessed using the
      Dutch Version of the Tampa Scale for Kinesiophobia (scale 17-68). A lifting task
      and an FCE were operationalizations of avoidance. FCE results were transformed
      into a single measure using the classification of the Dictionary of Occupational
      Titles (FCE-DOT, scale 1-5). Correlations between the variables were calculated.
      The results are: kinesiophobia mean 41.6 (SD 7.3), lifting mean 29.5 kg (SD
      11.6), FCE-DOT mean 3.6 (SD 0.6). Correlations between kinesiophobia and lifting
      was r = 0.01 (p = 0.93) and between kinesiophobia and FCE-DOT was rho = -0.04 (p
      = 0.75). The results indicate that the patients were substantially kinesiophobic,
      yet they were able to lift a mean of 29.5 kg and were physically able to perform
      moderate to heavy work. The strength of the correlations was very low. The
      relationship between kinesiophobia and avoidance, operationalized as lifting and
      an FCE, could not be confirmed in this study.

PMID- 14671990
TI  - Psychosocial factors and functional capacity evaluation among persons with
      chronic pain.
AB  - Psychosocial factors have been found to have a significant impact on functional
      activity, particularly among persons with chronic pain. While various systems
      have been developed to assess functional limitations through functional capacity
      evaluation (FCE), assessment of psychosocial factors that may impact function
      have been largely ignored. This paper examines the existing literature on
      psychosocial factors and FCE performance. Given that there are few studies that
      have directly addressed this issue, the paper also examines psychosocial factors
      that have been found to influence function in persons with pain. The results of
      the literature review indicate that few psychosocial factors have been found to
      be directly associated with FCE and functional measures, although many are
      related to various measures of disability. The strongest evidence that
      psychosocial factors are related to functional performance is based on the
      studies examining the association between functional activity and pain-related
      fear, self-efficacy, and illness behavior. Psychosocial factors have also been
      shown to influence measures of sincerity of effort often obtained during FCE.
      Proposals for modifying FCE assessment are given based on the available data, as
      well as suggestions for future research.

PMID- 14671992
TI  - Construct validity of a kinesiophysical functional capacity evaluation
      administered within a worker's compensation environment.
AB  - The construct validity of a kinesiophysical Functional Capacity Evaluation (FCE)
      administered within a worker's compensation context was examined. A cross
      sectional study design was employed. Clinical and demographic information on
      workers' compensation claimants was extracted from a rehabilitation facility's
      database. Measures of interest were the Isernhagen Work Systems' (Duluth, MN)
      FCE, the Pain Disability Index (PDI), and a pain visual analogue scale (VAS). A
      multitrait Pearson correlation matrix was created to observe the pattern of
      relationships between variables. The sample consisted of 321 subjects with work
      related, medically stable low back pain of median duration of 307 days. FCE
      performance was moderately correlated with the PDI (r = -0.44-0.52) and with the
      pain VAS (r = 0.34-0.45). Pain intensity was correlated highly with the PDI (r =
      0.79). The moderate relationship between FCE and the PDI supports the construct
      validity of FCE as a functional measure. However, kinesiophysical FCE performance
      was not unrelated to pain severity ratings as purported.

PMID- 14671993
TI  - Upper lifting performance of healthy young adults in functional capacity
      evaluations: a comparison of two protocols.
AB  - The objectives of this study were to explore the concurrent validity of test
      results of upper lifting tasks of the Ergo-Kit FCE and the Isernhagen Work
      Systems (IWS) FCE. Seventy-one healthy young adults performed 5 upper lifting
      tests with at least 5 min of rest in between. The lifting tests included 3
      standard protocols and 2 modified protocols. Three criteria for concurrent
      validity were established: 1) Pearson correlation higher than .75, 2)
      nonsignificant two-tailed t test, and 3) mean difference smaller than 5 kg. The
      results showed that none of the criteria were met for the standard protocols. For
      the modified protocols criteria 2 and 3 were not met. Individual differences
      larger than 10 kg were found for both standard and modified protocols. It was
      concluded that the standard protocols for upper lifting tasks of the Ergo-Kit FCE
      and the IWS FCE do not meet the criteria for concurrent validity and can,
      therefore, not be used interchangeably.

PMID- 14671994
TI  - [Pathophysiology and clinical implication of obstructive nephropathy].
AB  - Obstructive nephropathy refers to the mechanical or functional changes in the
      urinary tract that interfere with normal urinary flow. Once obstruction is set,
      it leads to progressive renal damage that is mainly characterized with
      tubulointerstitial fibrosis. Here we reviewed the pathophysiology of urinary
      tract obstruction and indicated future therapeutic options. Following complete
      unilateral ureteral obstruction, there is a progressive fall in renal blood flow
      and glomerular filtration rate, and is a increase in intratubular pressure. These
      events activate the plasma and tissue renin-angiotensin systems (RAS). It has
      been proved that upregulated angiotensin II is one of the crucial factors those
      are responsible for the subsequent deleterious process. Angiotensin II induces
      transforming growth factor-beta, which causes overproduction of extracellular
      matrix (ECM) proteins like collagen, fibronectin, etc. The ECM proteins are
      dominantly accumulated in tubulointerstitium and result in deterioration of renal
      function. Along with the activation of the RAS, tissue ischemia and mononuclear
      leukocyte infiltration also modulate the fibrotic changes. The process from the
      RAS activation to renal fibrosis is observed not only in obstructive nephropathy
      but also in other renal diseases and is called the Final Common Pathway.
      Mechanical release of the obstruction is to perform in terms of the treatment,
      however, several promising pharmaceutical options are now under investigation.

PMID- 14671995
TI  - [Long-term followup of water and solute metabolism in intestinal urinary
      diversion and the effect of diuresis; a 4-years observation in a unilateral ileal
      conduit model in dog].
AB  - PURPOSE: An intestinal segment interposed in the urinary tract can influence the
      water-solute balance of the patients with urinary diversion. It seems necessary
      to know whether such influence is changeable with the lapse of time and is also
      important to know whether diuresis is beneficial or not to minimize the effect of
      intestinal urinary diversion. MATERIALS & METHODS: In 8 female mongrel dogs a
      unilateral ileal conduit urinary diversion was constructed in the right
      nephroureteral units using a 20 cm segment of the ileum. After two months,
      separate urine for exactly 3 hours was collected from the conduit stoma and the
      bladder catheter, and analysis was made on each solute in the urine. In 4 dogs
      surviving for 4 years with stable renal function the examinations were repeated
      to compare with previous results. Furthermore, the effect of diuresis on the
      water and solute excretion was examined using 6 dogs. RESULTS: Water was
      reabsorbed or excreted from the ileal conduit according to the osmolality of the
      urine. No significant change was observed 4 years after operation. Urinary solute
      excretion and osmolality of the diverted side were always lower than those of
      intact side throughout the period. Creatinine clearance was not influence by the
      interposition of an ileal segment in the urinary tract in any periods. Excretion
      of water and reabsorption of solute was accelerated under oliguric condition and
      significant reabsorption of creatinine was observed in this condition.
      CONCLUSION: In the experimental observation using canine model with unilateral
      ileal conduit urinary diversion no significant differences were observed in water
      and solute metabolism between the early period and 4 years after operation.
      Diuresis appeared to be favorable to minimize the reabsorption of urinary solute
      from the ileal conduit.

PMID- 14671996
TI  - [The consequence after introduction of clean intermittent catheterization (CIC)
      in children with neurogenic bladder dysfunction secondary to spina bifida--the
      comparison of patients with and without upper urinary tract dilation at the time
      CIC was introduced].
AB  - PURPOSE: The aim of current study was to review the consequence after
      introduction of clean intermittent catheterization (CIC) in children with
      neurogenic bladder dysfunction secondary to spina bifida. PATIENTS AND METHODS:
      We retrospectively reviewed the records of 34 children (19 girls and 15 boys)
      presenting our clinic in a 18-year period. The patients were divided
      concentrating on the radiological upper urinary tract findings when CIC was
      introduced. 18 children had dilated upper urinary tract. In these patients, 10
      children already had dilated upper urinary tract at first visiting to our
      clinic(group A). In remaining 8 patients, dilatation of upper urinary tract was
      found out in the course of followup (group B). 16 children had normal upper
      urinary tract when CIC was introduced. In 7 patients, CIC was applied for post
      void residual and urinary tract infection (group C). In remaining 9 patients, CIC
      was introduced for urodynamically low compliance bladder (group D). RESULTS: In
      group A, 5 patients underwent enterocystoplasty and 3 patients underwent anti
      reflux surgery consequently. Two patients, including 1 patient who underwent
      enterocystoplasty, have chronic renal dysfunction. In group B, 3 patients
      underwent enterocystoplasty and 2 patients underwent anti-reflux surgery. In
      group C, all patients have normal upper urinary tract. In group D, 8 patients
      have normal upper urinary tract. However, 1 patients underwent enterocystoplasty
      for low compliance bladder with vesicoureteral reflux (VUR). CONCLUSION: Some
      patients show the improvement of dilated upper urinary tract or VUR after
      introduction of CIC. However, enterocystoplasty or anti-reflux surgery was needed
      for many patients to prevent upper urinary tract deterioration. The patients whom
      CIC was introduced for postvoid residual and urinary tract infection have not
      shown any deterioration of upper urinary tract. The efficacy of CIC for
      incontinence was poor because many patients have urethral sphincter incompetence.

PMID- 14671997
TI  - [Transurethral resection in saline (TURis): a newly developed TUR system
      preventing obturator nerve reflex].
AB  - PURPOSE: We developed an innovative transurethral resection system (TURis)
      consisting of a uniquely-designed generator and a resectoscope. The obturator
      nerve is protected from troublesome reflexes during TURis because the high
      frequency current delivery route is via the resection loop to the sheath of the
      resectscope and not via a patient plate. After extensive preclinical evaluation
      and verification of the system using an animal model to ensure efficacy as well
      as operational safety, TURis was conducted for treatment of superficial bladder
      cancer and benign prostatic hyperplasia. MATERIALS AND METHODS: In preclinical
      experiments swine bladder wall was transurethrally resected using the system in a
      saline environment. The results were compared with data obtained from an
      identical resection using the conventional system using sorbitol solution
      irrigation. Electrolytic contents were measured after TUR for comparative
      evaluation vis-a-vis corresponding pre-TUR data. Also, the depth of heat
      degeneration was measured in the resected tissue. From December, 2000 to June,
      2002, TURis was performed in 25 cases of superficial bladder cancer and 30 cases
      of benign prostatic hyperplasia (BPH), using saline irrigation. All 55 cases were
      performed under spinal anesthesia without an obturator nerve block. The output
      power was set at 280 W for cut and 120 W for coagulation. A smaller electrode
      than those used in conventional TUR was used to improve the cutting efficacy.
      Occurrence of obturator nerve reflexes, difference of hematocrit and electrolytic
      contents before and after TURis, operation time and total volume of irrigated
      saline were evaluated. RESULTS: TURis in animal model: No adductor contraction of
      a lower limb was observable except for minimal creeping during the resection of a
      site close to the urethra. There were no apparent anomalies relative to the blood
      electrolyte content after TURis. No difference was observed in the mean depth of
      heat-degeneration tissue change compared with the conventional system. TURis for
      bladder cancer and BPH: No additional skills were required for TURis compared to
      conventional TUR. No obturator nerve reflex was observed except for a clinically
      insignificant thigh movement in one case of bladder cancer. The post-TURis blood
      tests manifested no significant anomalies in blood electrolyte content. Mean
      operation time for bladder cancer and BPH were 32 and 42 minutes respectively.
      Mean volumes of saline consumed during TURis were 6,083 ml for bladder cancer and
      16,100 ml for BPH. CONCLUSIONS: TURis worked effectively in a saline-irrigated
      environment. It does not need a patient plate and obturator nerve block even in
      cases of bladder cancer on the lateral wall. In addition, saline was both safe
      and cost-effective compared to non-electrolytic solution as irrigant for TUR of
      BPH. This suggests that TURis may have more applications than conventional TUR.

PMID- 14671998
TI  - [Non-ischemic partial nephrectomy using microwave tissue coagulator].
AB  - PURPOSE: The indications and the safety of non-ischemic partial nephrectomy using
      a microwave tissue coagulator were studied. MATERIALS AND METHODS: Non-ischemic
      partial nephrectomy was performed on 17 kidneys of 16 patients using a microwave
      tissue coagulator. The diagnosis was renal tumor and renal stones in eleven and
      five patients, respectively. Renal tumors were less than 4 centimeters in
      diameter, while the stones were associated with a caliceal diverticulum or
      secondary cortical atrophy. Excision of the tumors was done via the
      retroperitoneal approach through an oblique lumbar incision. The needle of the
      microwave tissue coagulator was inserted around the tumor (stone) 10 to 20 times,
      and the coagulator was activated. Then the tumor (stone) was excised with a sharp
      knife or scissors. Patients were encouraged to walk on the first postoperative
      day. RESULTS: Vascular clamping was necessary in one patient to reduce bleeding.
      Nephrectomy was done after partial nephrectomy in one patient because it was
      difficult to close the urinary collecting system after it was widely exposed.
      Although urine leakage was seen postoperatively in two patients, it ceased
      spontaneously at 14 and 23 days after surgery. Postoperative complications
      developed in one of seven patients (14%) with protruding renal tumor, in three of
      five patients (60%) with non-protruding renal tumor and in two patients with
      renal stone. Allogenic or autologous blood transfusion was not necessary, nor was
      any bleeding noticed post-operatively. In one patient, atrophy of the renal
      parenchyma occurred gradually after surgery and function was eventually lost.
      However, renal function was well preserved and recurrence of the problem was not
      observed in the other 15 patients, excluding one who died of esophageal cancer.
      CONCLUSIONS: The microwave tissue coagulator is a useful surgical instrument for
      non-ischemic partial nephrectomy, not only in patients with renal tumors but also
      in patients with complicated kidney stones. However, non-protruding renal tumor
      in a patient with solitary kidney should be avoided for this surgery. Thermal
      injury to the renal parenchyma or large vessels should be avoided and urine
      leakage from the collecting system should be meticulously treated during the
      operation.

PMID- 14672000
TI  - [A case of haemangiopericytoma of the spermatic cord].
AB  - A case of haemangiopericytoma of right spermatic cord is reported. A 50-year old
      male presented with a month-lasting painless swelling of right scrotum.
      Ultrasonography revealed a soft tissue mass in right spermatic cord, which was
      about 3.5 cm in diameter. Right high inguinal orchiectomy was performed. The
      tumor was solid, smooth surfaced and well circumscribed. Histologically, the
      tumor had many capillary vessels and short spindle calls around the vessels. On
      the silver impregnation, argyrophil fibers surrounded the tumor cells.
      Immunohistologically, tumor cells were positive for CD34 antigen and negative for
      factor VIII antigen. The mitotic rate was 2 per highpower field. Accordingly,
      this tumor was diagnosed as benign haemangiopericytoma. The patient is doing well
      without any sign of recurrence, as of 30 months post-operatively.
      Haemangiopericytoma is a rare neoplasm of pericyte origin. It commonly occurs in
      retroperitoneum and lower extremities. To our knowledge, only two cases of
      malignant haemangiopericytoma of the spermatic cord was reported, and this case
      is the first benign case of the spermatic cord.

PMID- 14671999
TI  - [A case report of BK virus nephropathy after an ABO-incompatible living kidney
      transplantation].
AB  - We present a case of 29-year-old female who underwent an ABO-incompatible living
      kidney transplantation from her father. The serum creatinine (s-Cr) level of this
      patient was stabilized about 1.1-1.2 mg/dl during the first 3 months after the
      transplantation. Thereafter, the function of allograft was deteriorated
      gradually. A biopsy performed on post-transplant day (PTD) 520 to evaluate a rise
      in creatinine revealed an interstitial nephritis and chronic renal allograft
      nephropathy. The renal function worsened persistently, although we increased the
      dosage of immunosuppressant subsequently. The following biopsy performed on PTD
      630 showed a suspicion of BK virus nephropathy, with a mass of tubular epithelial
      nuclear inclusions and an interstitial nephritis. The diagnosis of BK virus
      nephropathy was confirmed on the immunohistochemistry staining using anti-SV40
      antibody and PCR analysis. Despite reducing the immunosuppressants, the function
      of the allograft worsened progressively and was lost on PTD 912.

PMID- 14672001
TI  - [Transcatheter arterial embolization for bleeding of prostatic artery after
      prostate biopsy].
AB  - We present a case of bleeding from the prostatic artery, complicating transrectal
      ultrasound (TRUS) guided prostate needle biopsy, that responded to transcatheter
      arterial embolization (TAE). A 62-year-old man with a serum PSA of 4.1 ng/ml was
      admitted to this institution for a prostate biopsy. He developed hypotension and
      marked abdominal distension 3 hours after undergoing TRUS guided prostate needle
      biopsy. CT scanning revealed a massive hematoma extending from the pelvis into
      the retroperitoneal space. Intra-arterial digital subtraction angiography (IA
      DSA) showed extravasation of dye from the right prostatic artery, indicating that
      it had been damaged during the biopsy procedure. The bleeding was successfully
      stopped with TAE, using 6 micro coils. TRUS guided prostate biopsy is generally
      considered a safe procedure, with few complications, and cases of massive
      hemorrhage into the retroperitoneal space are extremely rare. In cases of
      arterial retroperitoneal bleeding such as this one, treatment with TAE is fast
      and accurate.

PMID- 14672002
TI  - [Pulmonary rhabdomyosarcoma generated during treatment of testicular tumor].
AB  - A 23-year-old male was admitted to our hospital for the management of pulmonary
      metastases. He had undergone right high orchiectomy, chemotherapy with four
      courses of PEB regimen (cisplatin, etoposide, bleomycin) and retroperitoneal
      lymph node dissection the previous year. The pathological findings showed mixed
      germ cell tumor (seminoma, yolk sac tumor, embryonal carcinoma) in the testis and
      mature teratoma in the draining lymph node. Two courses of salvage chemotherapy
      using a VIP regimen (etoposide, ifosfamide, cisplatin) were performed after
      diagnosis of pulmonary metastases, but had no affect on tumor size. Video
      assisted excision of pulmonary metastases was then performed, giving a
      pathological diagnosis of rhabdomyosarcoma in all three resected tumors. The
      operation was followed by three courses of CYVADIC (cyclophosphamide,
      vincristine, adriamycin, dacarbazin) chemotherapy and oral cyclophosphamide, as a
      small residual tumor was suspected. These chemotherapeutic interventions have
      appeared effective, with no apparent recurrence of lesions at present, one year
      after the excision of pulmonary metastases.

PMID- 14672003
TI  - [Central and peripheral nerve disorder induced by interferon alpha therapy for
      renal cell carcinoma].
AB  - Interferon alpha (IFN-alpha) therapy was conducted for a male patient aged 70
      years old, who underwent a two-stage radical nephrectomy for bilateral renal cell
      carcinoma with multiple pulmonary metastasis. He was hospitalized due to leg
      weakness and disorientation 45 days after this treatment was started. We
      discontinued INF-alpha therapy immediately after neurologists indicated the
      disorder of the central and the peripheral nervous systems induced by the
      administration of this cytokine. Steroid pulse therapy was effective to resolve
      the patient's neurological symptoms. To our knowledge, this is the first case of
      the side effects on both central and peripheral nervous systems by IFN-alpha
      therapy for renal cell carcinoma.

PMID- 14672004
TI  - [Ureteral and bladder metastases of renal cell carcinoma following synchronous
      renal cell carcinoma and bladder cancer; a case report].
AB  - A 73-year-old man presented with gross hematuria. Ultrasonography and
      computerized tomography showed small bladder tumors and a left renal mass
      protruding to renal pelvis. Transurethral resection of bladder tumor and
      ureteroscopic tumor biopsy were performed, and pathological examinations revealed
      transitional cell carcinoma in the bladder and renal cell carcinoma in the
      kidney. He underwent left radical nephrectomy. A 4-month postoperative cystoscopy
      revealed a solitaly non-papillary tumor in the bladder. Transurethral resection
      was performed and pathological diagnosis was metastasis from renal cell
      carcinoma. At that time, multiple metastases to ureteral stump and lung were
      found. He had undergone palliative treatment because of his poor general
      condition until he died 26 months postoperatively. Care should be taken for
      management of ureteral stump when diagnostic ureteroscopy was done for renal cell
      carcinoma invading the renal pelvis.

PMID- 14672005
TI  - [Role of apoptosis in infectious diseases].

PMID- 14672006
TI  - Risk of acquiring zoonoses by the staff of companion-animal hospitals.
AB  - The aim of this study was to obtain information on the risk of companion-animal
      hospital staff members acquiring zoonotic diseases. We surveyed veterinary
      technicians to estimate the rate of acquisition of zoonoses from pets while
      working in companion-animal hospitals. About one in five veterinary technicians
      (19.4%) reported acquiring zoonotic infections in their small-animal practice.
      The rate of acquisition of zoonoses by those who had worked for more than 5 years
      was significantly higher than by those who had worked for less than 1 year (p <
      0.001, odds ratio: 6.74). The list of zoonoses included the flea bites (62.3%),
      dermatophytosis (26.9%), cat-scratch disease (16.0%), tick bites (9.0%), and
      pasturellosis (6.1%). A small number of veterinary technicians had been infected
      with Q fever, toxoplasmosis, parrot fever, salmonellosis, tetanus,
      campylobacteriosis, or scabies.

PMID- 14672007
TI  - [Cytotoxic effect and influence of povidone-iodine on wounds in guinea pig].
AB  - Cytotoxicity and effect on guinea pig wounds were compared with three kinds of
      10% povidone-iodine solution (isodine, neojodine, J-iodine) and povidone-iodine.
      It gave the following results: 1. In the Chang conjunctiva cell where remarkable
      toxicity was observed in the used cell line, the toxicity emphasized was 10 times
      using povidone-iodine < J-iodine < neojodine < isodine. In addition, a toxic
      difference was recognized between cells, in the order of Chang conjunctiva > SIRC
      > FRSK > human fibroblast for isodine and neojodine. 2. As for the influence on
      cells achromatized in sodium thiosulfate, alteration was not recognized in
      isodine, J-iodine using half-maximum cytotoxicity concentrations (CC50), and, in
      neojodine and povidone-iodine, elimination of drug toxicity was recognized in
      Chang conjunctiva/FRSK cells. 3. Strong toxicity was seen in isodine and
      neojodine in the toxicity test using colony formation method, however on washing
      with PBS (-), an easing of the toxicity effect could be seen to 0.01%. 4.
      Polyoxythylene nonylphenyl ether, NP-10 was the most toxic in the used
      surfactants in this study, and the toxicity by 100 times when compared with
      sodium polyoxyethylene lauryl ether sulfate, SBL-2N. Prominent sensitivity was
      observed in Chang conjunctiva cells with regard to the cell line and subsequently
      showed toxicity in order of SIRC > FRSK > human fibroblast. Remarkably, the
      difference between solutions of isodine and J-iodine was made more clear from the
      5th culture. 5. In this study, significantly guinea pig wounds, povidone-iodine
      blocked all examples significantly recognized as dallying by distance between
      epidermal cells. In addition, isodine was meaningful area. Although their ware
      not offer the significant differences, the solutions obstructed the sliding of
      epidermal cells in comparison with povidone-iodine, and a delaying tendency of
      inflammation was also recognized. The toxic difference between povidone iodine
      solutions was regarded as the influence of surfactants added to the povidone
      iodine. Based on this foundation study, more detailed clinical testing is
      necessary in determine where sterilization to wounds/mucosa/eyes with solutions
      containing additive is a suitable panpractice or not.

PMID- 14672008
TI  - [Evaluation of national surveillance for echinococcosis in Japan, 1999 to 2002].
AB  - National echinococcosis surveillance has been performed since April 1999 when it
      was stipulated as a Category IV Disease under the Infectious Diseases Prevention
      Law. During the last 4 years of surveillance, 7 cases of unilocular hydatid
      disease (age range 27-81 years; median age 56 years) and 43 cases of alveolar
      hydatid disease (age range 24-83 years; median age 64 years) have been reported.
      There was an increase in the number of reported cases of alveolar hydatid with
      age, and the greatest number of reported cases occurred in the age group > or =
      70 years. Thirty-three of the reported echinococcosis cases had clinical
      symptoms. The greatest number of echinococcosis was reported from health centers
      in Hokkaido; 94% of all reported cases (47/50) were from this island. After
      classifying Hokkaido into six regional districts and analyzing cases by district,
      we found the greatest number of reported cases to be from the Nemuro-Abashiri
      Kushiro region (16 cases) and the Ishikari-Shiribeshi-Iburi region (15 cases).
      However, the greatest number of reported cases per 100,000 residents was found to
      be from the Souya-Rumoi region (2.05/100,000) and the Nemuro-Abashiri-Kushiro
      region (2.00/100,000). As the incubation period of echinococcosis is thought to
      be several years or more, the current data shows the infection rate from several
      years ago. In order to better understand the current infection rate of
      echinococcosis, we recommended implementing a seroepidemiological surveillance in
      addition to the present surveillance.

PMID- 14672009
TI  - [Incidence and prevalent types of Norwalk virus, Sapporo virus and human
      astrovirus in pediatric gastroenteritis in Hiroshima Prefecture].
AB  - The incidence and prevalent types of Norwalk virus (NV), Sapporo virus (SV), and
      human astrovirus (HAstV) in pediatric gastroenteritis in Hiroshima Prefecture
      were investigated in 7 cold seasons, between 1995/96 and 2001/02. The incidences
      of NV, SV, and HAstV were 23.6% ranging from 16.3 to 34.4, 2.5% ranging from 1.5
      to 4.7, and 3.2% ranging from 1.5 to 6.0, respectively. The peak of the incidence
      of NV was found in November and December. No accumulation of monthly incidence in
      SV or HAstV was noted. Most NVs detected belonged to genogroup II. A probe type
      of G2F, according to Fukuda et al., was predominant in NV, followed by G2E and
      G2B. The probe types of LON and SAP, according to Vinje et al., were predominant
      in SV. Serotype 1 was predominant in HAstV.

PMID- 14672010
TI  - [The study on efficacy of oseltamivir for influenza A in children].
AB  - From January 2001 to July 2002, we investigated the duration of fever, the
      duration of hospitalization, the frequency of antipyretic use, and other clinical
      symptoms of 162 inpatients with influenza A virus infection, and compared them
      with oseltamivir-treated, amantadine-treated, and untreated groups. The duration
      of fever and the duration of hospitalization treated were significantly shortened
      in the oseltamivir-treated group than in the amantadine-treated group and
      untreated group. There was no difference in the duration of fever between
      patients treated by oseltamivir at 2 mg/kg/day and those at 4 mg/kg/day. The
      frequency of antipyretic use was lower in the oseltamivir-treated group than in
      the other group. No difference was observed in the duration of fever and the
      frequency of antipyretic use between patients treated by oseltamivir with
      antibiotics and those by oseltamivir alone. The complications such as vomiting,
      abdominal pain, irritability were observed in 9% of patients treated by
      oseltamivir. But those symptoms were not serious, and the rate of complications
      in the oseltamivir-treated group was lower than that in untreated group. In
      conclusion, oseltamivir is safe and effective in the treatment of influenza virus
      infection in children, and it may reduce the amount of antibiotics and
      antipyretic use.

PMID- 14672011
TI  - [A case of ventriculitis with bacterial meningitis occurred during the treatment
      of liver abscess].
AB  - A 47-case-year old male was admitted to our hospital because of high fever and
      general fatigue. He had no immune deficiency, and had no other disease in his
      past history. On admission, the white blood cell count and C-reacted protein were
      severely elevated (18,700/microliter, 27.7 mg/dl, respectively) and abdominal CT
      revealed multiple low density, From these results, he was diagnosed as liver
      abscess. Intravenous MINO and SBT/CPZ injection were started. On the fifth
      hospital day, he suffered from headache and nuchal rigidity. The clinical data
      revealed the cerebro-spinal fluid (CSF) counting 8,336 cells/mm3 (mononuclear
      8,000,) protein at 119 mg/dl, and sugar 42 mg/dl. CSF cultures were negative, but
      Klebsiella was recognized in the blood culture and drainage fluid in liver
      abscess. This condition was diagnosed as bacterial meningitis and antibiotics
      were changed to intravenous CTRX and MEPM. Furthermore we administered oral PSL
      and intravenous steroid-pulse therapy. After these combination therapies his
      condition improved gradually. After 40 hospital day, however, he suddenly had
      double vision, Axial FLAIR (SE6,000/120) image revealed with high signal
      intensity at 4th ventricle. Intravenous MEPM was administered again. On the 60th
      hospital day, double vision was gradually improved and abnormal intensity at 4th
      ventricle was almost disappeared. This case may provide us a considerable
      suggestion on the treatment of bacterial meningitis.

PMID- 14672012
TI  - [A successful treatment with micafungin of candidemia due to Candida krusei].
AB  - We report a case of candidemia due to Candida krusei after subarachinoid
      hemorrhage. A 51 year-old male patient consulted us for high fever and increase
      of CRP 10 days post operation against subarachinoid hemorrhage. There was a
      temporary decrease in the CRP after administration of ceftazidime (CAZ) but it
      again when treatment with CAZ was stopped. Because of detected Candida sp. by
      blood culture, fluconazole was administered i.v. for 5 days, but C. krusei was
      positive during the treatment. Therefore, fluconazole was replaced with
      micafungin. The patient became better after the administration with micafungin
      for 14 days without side effect. Micafungin is effective against candidemia due
      to C. krusei.

PMID- 14672013
TI  - [Two siblings with allergic purpura following Salmonella O9 enterocolitis].
AB  - Two siblings with allergic purpura after Salmonella O9 infection were reported. A
      girl (patient 1) aged 4 years and 4 months started to have knee joint pain and
      abdominal pain followed by purpura of the lower extremities and was referred to
      us for treatment of allergic purpura. She had contracted enterocolitis one month
      before visiting our hospital and Salmonella enteritidis was identified. During
      the course of the illness she had nephritis associated with allergic purpura.
      However, she made a favorable progress and proteinuria and hematuria disappeared
      within 6 months. A boy (an elder brother of patient 1) aged 6 years was admitted
      to our hospital because of the allergic purpura. He similarly had contracted
      Salmonella enterocolitis. He had severe gastro-intestinal symptoms including
      abdominal pain, vomiting and bloody stool, which rapidly subsided after
      initiation of treatment with intravenous hyperalimentation combined with
      prednisolone. It is possible that allergic purpura in our patients was closely
      associated with Salmonella enteritidis infection. Further accumulation of cases
      is a requisite to clarify an association of Salmonella enteritidis infection with
      allergic purpura and pathogenesis of allergic purpura.

PMID- 14672014
TI  - [A successful treatment of progressive necrotizing myositis caused by Aeromonas
      veronii biotype sobria].
AB  - We report a 52 year-old patient with malignant lymphoma who developed necrotizing
      soft tissue infection in the left lower extremity by Aeromonas veronii biotype
      sobria during a neutropenic period after intensive chemotherapy. We decided to
      amputate the involved leg when signs and symptoms of necrotizing myositis were
      progressing despite administration of sensitive antibiotics. He survived with
      subsequent intensive supportive care. It is to note that even though the
      patient's neutrophil count is zero, he or she should be treated aggressively by
      drainaging the lesion or even amputation of the involved extremities in
      combination with proper antibiotics.

PMID- 14672015
TI  - [Emergency coronary artery bypass grafting for acute coronary syndrome with
      preoperative intraaortic balloon pumping; comparative surgical outcome and long
      term results].
AB  - With recent technical improvements in catheter interventional therapy,
      percutaneous coronary intervention (PCI) has now become the treatment of first
      choice for acute coronary syndrome (ACS). The objective of the present study was
      to evaluate critically the timing of coronary artery bypass grafting (CABG) for
      severe ACS with preoperative intraaortic balloon pumping (IABP). Since 1994, a
      total of 70 patients have gone emergency or urgent CABG for ACS. Of 70 patients,
      50 patients required preoperative IABP. There were 22 patients (17 men, 5 women)
      with acute myocardial infarction (AMI), with a mean age of 67.7 years, and 28
      patients (19 men, 9 women) with unstable angina pectoris (UAP), with a mean age
      of 69.2 years. There was a significant difference, between AMI and UAP, in the
      prevalence of emergency operation (95.5% vs 25.0%), in preoperative cardiogenic
      shock (81.8% vs 17.9%), in the level of preoperative CPK-MB (196.7 IU/l vs 2.0
      IU/l) and in preoperative ejection fraction (41.8% vs 47.3%). Two patients in AMI
      required percutaneous cardiopulmonary support (PCPS). Thirteen patients in AMI
      and 22 patients in UAP presented left main trunk (LMT) disease. Of the 13 LMT
      patients in AMI, 4 patients were AMI due to acute occlusion in the LMT. The AMI
      patients received 2.45 distal anastomoses on average, while the UAP patients 3.14
      distal anastomoses (p = 0.019). Excluding the mean number of distal anastomoses,
      there was no difference in the intraoperative technical factors, such as aortic
      cross clamping duration, cardiopulmonary bypass duration, rate of complete
      revascularization, between AMI and UAP. There were postoperative significant
      differences in low cardiac output syndrome (LOS) [45.6% in AMI vs 3.6% in UAP]
      and in prolongation of mechanical ventilation (59.1% in AMI vs 14.3% in UAP). The
      hospital mortality was 9.1% (2/22) in AMI, and 3.6% (1/28) in UAP, with no
      significant difference. Of these 3 patients, 1 patient died from perioperative
      cerebrovascular accident (CVA), another from LOS, and the other from
      postoperative mesenteric ischemia, with an overall mortality of 6.0% (3/50). The
      overall patency rate of the grafts was 100% in AMI and 96.6% in UAP. The 5-year
      survival rate excluding in-hospital death was 72.5% in AMI, and 89.6% in UAP. The
      5-year-cardiac event-free rate was 77% in AMI and 89.4% in UAP. The overall
      survival rate, and cardiac event-free rate, at 5 years was 80.8%, and 83.8%,
      respectively. In conclusion, for ACS cases, especially UAP cases of LMT, in which
      symptoms, findings of ischemia and hemodynamics are stabilized by medical
      intervention including IABP; emergency surgery could be avoided immediately after
      coronary angiography. Recovery in the ischemic myocardium is intended by IABP,
      and urgent surgery should be performed after sufficient and precise preoperative
      examinations. An improvement not only in the perioperative but also long-term
      results can be expected by performing complete revascularizations.

PMID- 14672016
TI  - [Surgical treatment for chronic hemorrhagic pyothorax].
AB  - A case of pleuro-pneumonectomy following arterial embolization for chronic
      hemorrhagic pyothorax occurring 40 years after artificial pneumothorax treatment
      was investigated. The patient was an 80-year-old male diagnosed with chronic
      hemorrhagic pyothorax after complaining of bloody sputum and difficulty breathing
      during exertion. The pyothorax space was conspicuously extended, and the
      mediastinal space was compressed. Although this condition was treated
      periodically over time by thoracentesis, pleuro-pneumonectomy was selected as a
      radical treatment. Since a large amount of hemorrhaging was expected during
      surgery, preoperative transcatheter embolization of the left lateral thoracic
      artery, the bronchial arteries and the left internal thoracic artery was
      performed. The amount of hemorrhaging during surgery from the feeding artery from
      the thoracic wall was 5,700 ml. There was an abundance of dilated blood vessels
      within the thickened pleura, and angiomatous structures were observed. Although
      symptoms improved following surgery, sudden massive hemorrhage was observed from
      the thoracic drain on the morning of the 79th postoperative day, and the patient
      died from hemorrhagic shock. Emergency thoracotomy was performed, and aortic
      rupture was observed on the origin of the left subclavian artery. Chronic
      hemorrhagic pyothorax has a peculiar pathology even for chronic pyothorax, and a
      large amount of hemorrhaging can be expected during surgery. Precaution must be
      taken for postoperative arterial hemorrhage caused by delayed inflammation.

PMID- 14672017
TI  - [Natural evolution of coronary artery ectasia after coronary artery bypass
      grafting].
AB  - Coronary artery aneurysm and ectasia, unusual angiographic findings, are
      considered as variant of atherosclerotic coronary artery disease. A 49-year-old
      man whose right coronary artery ectasia had progressed to large aneurysm,
      accompanied by advanced obstructive coronary artery disease, 6 years after the
      initial coronary artery bypass grafting. It was treated with ligation of aneurysm
      and distal bypass grafting under cardiopulmonary bypass. Fragile fresh clot was
      formed within the aneurysm irrespective of coumadin therapy as a standard regimen
      for the coronary artery ectasias. We will discuss the surgical management for the
      dilated coronary artery with significant coronary stenosis.

PMID- 14672018
TI  - [Effects of Na(+)-HCO3- symport on ischemia/reperfusion injury; Na+/H+ exchanger
      inhibitor and buffer composition].
AB  - We studied the impact of perfusate buffer composition on the relative degree of
      protection afforded by Na+/H+ exchanger (NHE) inhibition during ischemia as
      opposed to during reperfusion. Isolated rat hearts were perfused with bicarbonate
      or HEPES-buffered medium. There was infusion of HOE 694 immediately before
      ischemia, during initial reperfusion, or during both of these periods. With
      bicarbonate-buffered medium, HOE 694 improved the post-ischemic recovery of left
      ventricular developed pressure (LVDP) when given before ischemia and before
      ischemia plus during reperfusion. In the presence of HEPES-buffered medium,
      however, HOE 694 significantly improved recovery of LVDP in all protocols. HOE
      694 also provided an almost complete recovery of LVDP (88 +/- 9% vs 30 +/- 7% in
      controls) when given before ischemia plus during reperfusion. In conclusion, our
      results suggest that the influence of NHE activity during reperfusion on the
      extent of functional recovery is modulated significantly by perfusate buffer
      composition.

PMID- 14672019
TI  - [Elucidation of one-lobe intrapulmonary metastasis route of primary lung cancer
      by means of long-term results].
AB  - OBJECTIVE: We hypothesized that the cause of one-lobe intrapulmonary metastasis
      of primary lung cancer is mainly lymphatic, and investigated by means of the long
      term outcome. METHODS: From 1988 to 2000, 860 patients underwent complete
      resection of primary lung cancer patients in our hospital without neoadjuvant
      therapy. Patients were classified into 4 groups: group A (n 0 pm 0, n = 573),
      group B (n 0 pm 1, n = 37), group C (n 1 pm 0-1, n = 122), and group D (n 2 pm 0
      1, n = 128). RESULTS: No significant difference was seen between groups in median
      age, sex ratio, histological cell type, or pathological tumor-size and p-factor.
      The rates of bi-lobectomy and pneumonectomy were higher in groups C and D than in
      groups A and B. The 5-year survival rate was 73% for group A, 57% for group B,
      43% for group C, and 28% for group D. The 10-year survival rate was 57% for group
      A, 45% for group B, 20% for group C, and 16% for group D. There was a significant
      difference (p < 0.0001) between 4 groups in the 5- and 10-year survival rate.
      CONCLUSION: The hypothesis that the cause of one-lobe intrapulmonary metastasis
      may be lymphatic was not incompatible with the long-term results.

PMID- 14672020
TI  - [Minimally invasive video-assisted thoracic surgery using radially expanding
      trocars].
AB  - We report a new and safer access device for thoracoscopic operation. This
      radially expanding trocar provides a smaller incision of skin and a lesser
      visceral, vascular or neural injury than a conventional cannula. Therefore, most
      of patients undergoing this operation do not feel much pain. Moreover, this
      device system is more cost effective than a conventional one. We prefer and
      recommend this minimally invasive technique for video-assisted thoracic surgery.

PMID- 14672021
TI  - [Ten cases of transverse aortic arch replacement using antlers graft technique].
AB  - Ten cases of total arch replacement were performed using the antlers graft
      technique. The patients consisted of 6 men and 4 women ranging in age from 34 to
      76 years (mean: 62.1 years). These cases included 7 cases of Stanford type A
      acute aortic dissection and 3 cases of fusiform aneurysm of the aortic arch.
      During surgery we formed a composite graft (antlers graft) by attaching 10, 12
      and 24 mm side branches to a 10 mm woven graft and under hypothermic circulatory
      arrest with retrograde cerebral perfusion (RCP), we first of all remodeled the
      neck vessels and re-established antegrade cerebral perfusion. We then remodeled
      the arch using another 24 mm graft and concluded surgery by anastmosing this
      graft to the antlers graft. Eighteen cases using the conventional technique, in
      which anastmosis is performed from the distal arch, needed 77 minutes on average
      for RCP. However, the antlers graft technique required only 46.2 minutes.
      Although 1 case each of cerebral complications was observed during both
      techniques, the antlers graft technique shortened the time required for emergence
      from the general anesthesia (4 hours vs 11.4 hours), the length of the stay in
      the ICU (6.0 days vs 7.3 days) and the total hospital stay (45.8 days vs 60.3
      days), compared to the conventional technique.

PMID- 14672022
TI  - [Left superior segmental resection for lung cancer with anomalous branching of
      the left A4 + 5; report of 2 cases].
AB  - We experienced with two cases of left superior segmental resection for lung
      cancer with the left A4 + 5 which arose from pars mediastinalis. Left superior
      segmental resection was performed on a 67-year-old female and an 81-year-old
      male. In both cases we divided A4 + 5 temporarily and anastomosed to pars
      interlobaris of the left pulmonary artery. As a result, it was able to perform
      safe division of bronchus. In cases with A4 + 5 arising from pars mediastinalis,
      operation is difficult and risky because A4 + 5 locates in front of the left
      upper lobe bronchus. It is safer to reconstruct A4 + 5 on pars interlobaris of
      the left pulmonary artery in such cases.

PMID- 14672023
TI  - [Aortic dissection presenting with neurologic sign; report of a case].
AB  - A 59-year-old man was admitted to our hospital for neurological deficit and left
      hemiplegia, presenting remission in the short time. Computed tomography(CT) of
      the brain was normal. CT of the chest showed a thoracoabdominal aortic dissection
      from the ascending aorta to the bilateral femoral artery, that involved all
      cervical arteries. The intimal flap separated the false and true lumens and there
      was flow in both lumens. That phenomenon can be due to the extension of the
      dissection along the aorta, occluding the origin of the cervical arteries and the
      change of the flow by the intimal flap. He was amputated his left leg below knee
      on the 1 postoperative day (POD), but discharged at 70 POD without neurologic
      complications.

PMID- 14672024
TI  - [Acute purulent pericarditis due to Haemophilus influenzae treated successfully
      with subxiphoid pericardial drainage; report of a case].
AB  - A surgical case of acute purulent pericarditis in 1-year 2-month old boy who
      developed pericardial tamponade rapidly is reported. A subxiphoid pericardiectomy
      through a median incision was performed. Haemophilus influenzae was isolated from
      the effusion. He recovered successfully with an administration of antibiotics
      after the drainage procedures and did not develop constructive pericarditis. Our
      experience suggested that early subxiphoid pericardial drainage was effective in
      treatment of acute purulent pericarditis.

PMID- 14672025
TI  - [Left atrial thrombus without mitral disease; report of a case].
AB  - A 76-year-old man was admitted to our hospital because of surgical treatment for
      mass in the left atrium(LA). Echocardiography and computed tomography(CT)
      revealed mobile mass in LA which had stalk at the left atrial appendage. It was
      difficult to distinguish myxoma from thrombus. LA mass has risk of sudden
      circulatory collapse and systemic emboli, so it is indicated for emergent
      operation. Mass resection with appendage was performed through the transseptal
      superior incision using cardiopulmonary bypass. Pathological diagnosis was
      thrombus. Most of LA thrombus were complicated with mitral stenosis, LA thrombus
      without mitral disease is rare. A few authors reported the useful of CT and
      echocardiography, but we could not lead to precise diagnosis from preoperative
      image.

PMID- 14672026
TI  - [Right-sided infective endocarditis with a large size vegetation].
AB  - A 2-year-old boy with ventricular septal defect(VSD) had suffered from right
      sided infective endocarditis with a vegetation 1.0 cm in size, involving
      pulmonary valve. Resection of the vegetation and partial resection of the
      pulmonary valve and patch closure of the VSD was performed after 3 weeks
      intravenous antibiotic therapy. In right-sided infective endocarditis, it is
      still unclear, however, which factors may be useful in predicting outcome or
      determining the need of surgical intervention. We recognize that following
      factors are the risk for need of surgical intervention. 1. persistent infection,
      2. sever right-sided heart failure, 3. multiple embolic episodes, 4. infected by
      Staphylococcus aureus, 5. infection involving the annulus of the valve, 6.
      infection of prosthetic valve, 7. vegetation which is floppy and greater than 1.0
      cm in size.

PMID- 14672027
TI  - [Apico-aortic conduit for severe aortic stenosis in elderly].
AB  - We described a case of an 84-year-old woman with end stage aortic stenosis in
      whom favorable results were obtained after constructing apico-aortic conduit
      bypass. The patient admitted due to complete atrio ventricular(AV) block and
      respiratory insufficiency. Although a permanent pacemaker was implanted, heart
      failure did not improve. Echocardiograms showed small aortic annulus and severe
      calcific aortic stenosis with a measured trans valve gradient of 100 mmHg. Since
      cardiac failure deteriorated and she lapsed into hypotension and acute renal
      failure, an emergency operation was performed. The left lateral thoracotomy was
      performed with cardiopulmonary bypass. A bioprosthetic valved conduit was
      anastmosed to the left ventricle apex. Another graft was anastomosed to the
      discending thoracic aorta. The operation was completed by anastomosing the
      tailored ends of the grafts together. Although the patient required hemodialysis
      for 2 weeks after operation, she was discharged on 57th day after operation
      without any complications. Apico-aortic conduit is considered to be an useful
      procedure for elderly patients who were not good candidates for conventional
      valve replacement.

PMID- 14672028
TI  - [Lung cancer with both sarcoid reaction and metastasis in the mediastinal lymph
      nodes; report of a case].
AB  - A 66-year-old man was admitted to our hospital for detailed investigation of an
      abnormal shadow on his chest X-ray. Chest radiography and computed tomography(CT)
      of the chest showed mediastinal lymphadenopathy and a tumor shadow in the left
      upper lobe. Biopsy of the mediastinal lymph nodes by mediastinoscopy showed that
      sarcoid nodules existed in all the biopsies nodes. Therefore, the lymphadenopathy
      was thought to be sarcoidosis or sarcoid reaction accompanied with lung cancer.
      Left upper lobectomy and dissection of hilar and mediastinal lymph nodes were
      performed. Although sarcoid nodules were seen in all the dissected lymph nodes,
      the cancer involved #5 and #14 lymph nodes. He died of brain metastasis 10 months
      after surgery.

PMID- 14672030
TI  - [Pulmonary sequestration associated with fungal infections; report of a case].
AB  - A 45-year-old female was admitted to our hospital complaining of cough and
      purulent sputum. Enhanced chest computer tomography(CT) showed that abnormal mass
      shadow in left lower lobe of the lung and an aberrant artery originated from the
      discending aorta and penetrated the lesion. Left lower lobectomy was performed
      and intralobar sequestration was diagnosed. Moreover, fungus which were suspected
      Aspergillus were found in the cystic lesion. The postoperative course was
      uneventful and she was discharged.

PMID- 14672029
TI  - [Chondromatous hamartoma of the lung with a unique demonstration on diagnostic
      imaging; report of a case].
AB  - A case of pulmonary hamartoma is reported with clinical, roentgenographical and
      histopathologic findings. The patient was a 53-year-old woman who had undergone
      right hemithyroidectomy for thyroid cancer 4 years before. An abnormal shadow,
      which was a non-clearly demarcated tumor, 2 cm in diameter, in the left middle
      lung field, was noted on her routine X-ray in February 2001. Physical examination
      and laboratory data revealed no significant findings, but computed tomography(CT)
      scans of the chest showed a gathering of small-sized high-density lesions in the
      nodule. She underwent left S8 segmentectomy on March 21, 2001. The pathology
      report on the frozen section was pulmonary hamartoma. Histopathologically, the
      lesion was characterized by a composition of bronchial epithelium, fat tissue and
      cartilage, with being diagnosed as a chondromatous hamartoma of the lung. The
      patient's postoperative course was uneventful, and she was discharged with no
      supportive therapy 14 days after the operation. To date, 14 months after the
      operation, the patient has been in good condition, without evidence of recurrence
      or distant metastasis on diagnostic imaging. This case is particularly
      interesting because a gathering of small-sized pulmonary hamartoma was
      demonstrated by imaging.

PMID- 14672031
TI  - [Mediastinal lymph-node carcinoma with no apparent primary lesion; report of a
      case].
AB  - A 57-year-old woman was admitted to our department because of a chest X-ray
      showing a mass shadow about 40 mm in diameter in the right side of the middle of
      the mediastinum. A chest computed tomography(CT) scan demonstrated a large tumor,
      adherent to the superior vena cava and right pulmonary artery. No other
      metastases and no primary tumor were found. The tumor was resected through median
      sternotomy. Intraoperative frozen section analysis showed that the mediastinal
      tumor was a metastatic lymph-node carcinoma. Postoperative examination, too, did
      not detect the primary lesion. Radiotherapy was given after the operation. This
      case was thought to be a very rare case of T0N2M0 lung cancer or primary
      mediastinal lymph-node carcinoma (yolk sac tumor).

PMID- 14672032
TI  - [Evaluation of pharyngeal swallowing elicited by fluid infusion using
      videoendoscopy in dysphagia patients].
AB  - The purpose of this study was to investigate the clinical value of assessing
      pharyngeal swallowing elicited by fluid infusion. Videoendoscopic examinations
      were performed in 126 patients with dysphagia, after injecting a fluid infusion
      into the pharyngeal cavity. Blue dye fluid was instilled into the unilateral
      vallecula through a catheter that was inserted into the biopsy channel of an
      endoscope. Pharyngeal swallowing elicited by the fluid infusion was classified
      according to 5 grades: grade 1, normal pharyngeal swallowing; grade IIa,
      laryngeal penetration before the triggering of pharyngeal swallowing; grade IIb,
      pharyngeal residue after swallowing; grade IIa + b; and grade III, no the
      pharyngeal swallowing. The recovery rates for oral intake using several
      approaches for dysphagia were 98% in grade I patients and 75% in grade IIb
      patients. However, the oral intake of food was more difficult in grade IIa, grade
      IIa + b and grade III patients. These results suggest that the classification of
      dysphagia based on the triggering and output situation of pharyngeal swallowing
      may be a useful guideline for demonstrating impaired oral food intake. We
      conclude that videoendoscopic examination using a fluid infusion is a valuable
      method for evaluating pharyngeal swallowing minus the influence of bolus
      transport from oral cavity to the pharynx.

PMID- 14672033
TI  - [A clinical study of 104 patients with tongue cancer and the relationship between
      DNA ploidy and prognosis in 41 cases].
AB  - One-hundred and four patients with previously untreated tongue cancer seen in our
      department between 1986 and 1998 were enrolled in a clinical study. The DNA
      ploidy patterns observed in fresh frozen specimens obtained from 41 patients were
      analyzed, and prognostic factors were investigated. According to the TNM
      classification (UICC 1997), 43 patients had stage I tumors, 29 had stage II
      tumors, 17 had stage III tumors, and 15 had stage IV tumors. The 5-year cause
      specific survival rates for each stage were 94.7%, 64.4%, 50.0% and 45.7%,
      respectively. The most frequent cause of death associated with the original
      disease was the recurrence of the disease in cervical lymph nodes (19/27, 70.4%).
      The occurrence of late cervical metastasis was high among patients with a T2N0
      disease. Patients with stage II disease should undergo elective neck dissection
      or be carefully monitored using ultrasonography. Among the 41 cases in which the
      DNA ploidy pattern was analyzed, diploid patterns were found in 30 cases and
      aneuploid patterns were found in 11. The 5-year cause-specific survival rate and
      the 5-year locoregional control rate were significantly lower for the aneuploid
      cases (18.2%, 38.9%) than for the diploid cases (66.5%, 69.8%) (p = 0.0003, p =
      0.0339). The incidence of distant metastasis was significantly higher among the
      aneuploid cases (6/11, 54.5%) than among the diploid cases (3/30, 10.0%) (p =
      0.0058). The ploidy pattern, as determined by flow cytometric DNA analysis, may
      reflect the malignancy grade of tongue cancers.

PMID- 14672034
TI  - [Voice rehabilitation after total laryngectomy using the Provox voice
      prosthesis].
AB  - Esophageal speech is the first choice for vocal rehabilitation in laryngectomized
      patients. However, shunt speech is a needed alternative for patients who cannot
      succeed at esophageal speech. Many kinds of voice prostheses, with good results,
      have been reported. Provox was selected for 15 laryngectomized patients who were
      treated in our department. Voice rehabilitation was successful in 13 patients.
      However, removal of the prosthesis was required in one patient because of stomal
      stenosis. Voice rehabilitation was not successful in one patient who exhibited
      esophageal stenosis. The rate of voice rehabilitation was not influenced by the
      extent of surgery, the dose of radiation, etc.. The maximum phonation time was
      more than 10 minutes in the 13 patients who succeeded at shunt speech. Prosthetic
      rehabilitation was requested by two patients who had been successful at
      esophageal speech. These results suggest that prosthetic voice rehabilitation may
      be indicated for a wide range of conditions.

PMID- 14672035
TI  - [CHEP with the total removal of the arytenoid on the tumor-bearing side].
AB  - A supracricoid laryngectomy with cricohyoidoepiglottopexy (CHEP) consists of the
      resection of the whole thyroid cartilage and paraglottic space, while preserving
      the cricoid cartilage, the hyoid bone, most of the epiglottis and the arytenoids.
      Laryngeal reconstruction is achieved be suturing the cricoid cartilage and the
      hyoid bone. This procedure is mainly indicated for large T2 glottic carcinomas
      and provides a complete resection and laryngeal preservation without requiring a
      permanent tracheostomy. Although bilateral arytenoids are usually preserved to
      ensure better laryngeal function after CHEP, we unavoidably had to remove the
      arytenoid on the tumor-bearing side during a complete resection performed in a 56
      year-old male with a rT2 tumor who had undergone radiation and demonstrated
      impaired vocal fold motion. Despite the resection of one arytenoid, the final
      laryngeal function proved to be satisfactory. CHEP should be utilized as an
      alternative surgical modality for conventional vertical partial laryngectomies or
      total laryngectomies. CHEP with the total removal of the arytenoid on the tumor
      bearing side may be a useful laryngeal preservation procedure for the treatment
      of patients with glottic carcinoma associated with an impaired vocal fold motion
      or a fixed vocal fold.

PMID- 14672036
TI  - [Mechanisms of selective neuronal death of cerebellar granule cell in organic
      mercury intoxication].

PMID- 14672037
TI  - [Study on the prevalence of Parkinson's disease: based on epidemiological
      surveys].

PMID- 14672038
TI  - [Malignant transformation of epithelial thymoma developed in HTLV-I pX transgenic
      rat by heterotopic transplantation and its molecular analysis].

PMID- 14672039
TI  - [Antigenic structures recognized by anti-beta 2-glycoprotein I autoantibodies].

PMID- 14672040
TI  - [High expression of macrophage migration inhibitory factor and its role in
      cellular proliferation and extracellular matrix production in keloid
      fibroblasts].

PMID- 14672041
TI  - [Induction of gene expression by TNF-alpha and steroid stimulations in cultured
      human umbilical vascular endothelial cells].

PMID- 14672042
TI  - [Expression of retroviral env protein and its antigenisity in the transgenic rat
      carrying human endogenous retrovirus gene, HERV-R].

PMID- 14672043
TI  - [Medico-legal application of hemoglobin analysis using CO-oximeter].

PMID- 14672044
TI  - [Efficacy of tuberculosis contacts investigation and treatment, especially of
      preventive therapy in infants and young children].
AB  - BACKGROUND: Although large clinical trials reported in 1960s suggested that
      preventive therapy in subjects with tuberculosis (TB) infection reduces the risk
      of developing TB by 70-90%, the therapy in our TB clinic seems to be more
      effectiveness. OBJECTIVE: We retrospectively evaluated the efficacy of the
      present contacts investigation, especially of preventive therapy for further
      improvement of TB control for children. METHODS: We examined 273 asymptomatic
      infants and children younger than five years who had household contacts with
      active TB patients and visited our clinic for contact investigation. After the
      diagnosis at the first visit to our TB clinic, they were treated and/or observed
      for at least two years to assess whether contact investigations and following
      treatment are appropriate. Since infants less than a year are underdeveloped in
      cell-mediated immunity and their tuberculous lymphadenopathy can be overlooked on
      standard chest radiographs, chest CT scans were added. RESULTS: At their first
      visit, 60 (22%) out of 273 subjects were diagnosed as TB, and 37 (14%) were
      suspected as TB. We treated them by combinations of anti-TB medicines including
      isoniazid and rifampin for six to 12 months, and they did not relapse during the
      observation period. Twenty-six subjects (9%) were diagnosed uninfected. However,
      a three-year-old girl developed bilateral hilar lymphadenopathy two months later
      when the reexamination was done. A hundred and fifty subjects (55%) were
      diagnosed to have TB infection. They received preventive therapy with isoniazid
      (10 mg/kg/day) for six months. Among them, a four-month-old boy developed TB
      disease soon after starting to take isoniazid and was treated by the combination
      of anti-TB medicines. Other 149 subjects completed the therapy, and none of them
      developed disease during the observation period. There was no increase in serum
      GOT and/or GPT to > 100 IU/L within one month after starting to take isoniazid.
      CONCLUSION: The present contacts investigations and treatments in our TB clinic
      are useful ways to find out and control TB diseases and infections, and it might
      be suggested to start the six-months preventive therapy after active TB has been
      ruled out in all infants and children who had close contacts with active TB
      patients for preventing TB disease and latent TB infection in the future even
      their clinical and laboratory examinations do not suggest infection.

PMID- 14672045
TI  - [Agranulocytosis due to anti-tuberculosis drugs including isoniazid (INH) and
      rifampicin (RFP)--a report of four cases and review of the literature].
AB  - We experienced 4 cases of agranulocytosis due to anti-tuberculosis drugs
      (rifampicin [RFP], isoniazid [INH], ethambutol [EB], streptomycin [SM] or
      pyrazinamide [PZA]) among some 6,400 tuberculosis patients who underwent
      chemotherapy over the past 20 years from 1981 to 2002 in our hospital, and the
      incidence rate of agranulocytosis was estimated at 0.06%. The 4 cases of
      agranulocytosis were as follows. CASE 1: A 51-year-old woman with right chest
      pain and fever was admitted to our hospital on Jan 4, 2001. The white blood cell
      (WBC) count was 5,200/microliter. The tubercle bacilli were cultured in her
      sputum. The treatment with INH 0.3, RFP 0.45, EB 0.75, PZA 1.2 g/day, allopurinol
      and teprenone was started on Jan 13. Pyrazinamide and allopurinol were stopped
      because of hyper-uric acidemia on Feb 7. Agranulocytosis and eosinophilia (WBC
      1,300 [Neut 1%, Ly 57%, Eos 35%]) developed on Feb 13. All drugs were withdrawn
      and G-CSF drug nartograstim 100 micrograms was injected subcutaneously for 3
      days. The WBC recovered to normal level and she was thereafter treated with INH,
      EB and Levofloxacin (LVFX) without any further trouble. Agranulocytosis in this
      case was supposed to be due to RFP. CASE 2: A 66-year-old man who had had
      nephrotic syndrome and hypothyroidism and has been treated with prednisolone 10
      mg/day was admitted to our hospital on Aug 9, 2000 because of miliary
      tuberculosis. The tubercle bacilli were cultured in his sputum and the treatment
      with INH 0.3, RFP 0.45, and EB 0.75 g/day were started on Aug 10, but it was
      withdrawn on Aug 17 because of general skin eruption. After re-starting treatment
      with EB and INH on Aug 24, RFP was added in small dosage (0.05 g) on Oct 12, but
      agranulomatosis (WBC 2,300/microliter [Neut 2%]) developed on Nov 21, and all
      drugs were withdrawn again. The G-CSF drug filgrastim was used once
      subcutaneously, and WBC recovered immediately. He was thereafter treated with
      INH, EB, LVFX successfully. Agranulocytosis was supposed to be due to RFP. CASE
      3: A 60-year-old woman without symptoms had abnormal chest roentgenograph, and
      consulted with our hospital on Aug 26, 2002. The broncho-alveolar lavage fluid
      was smear and culture-negative, but PCR-TB positive, and the case was diagnosed
      as pulmonary tuberculosis. Treatment with INH 0.3, RFP 0.45, EB 0.75, PZA 1.2
      g/day, alloprinol 300 mg and rebamipide 300 mg/day was started on Sept. 5, 2002.
      Late in September, she complained of appetite loss. The laboratory data on Oct 3
      revealed WBC 900/microliter (Neut 1%, Ly 94%), aspartate aminotransferase (AST)
      199 IU/l, and alanine aminotransferase (ALT) 253 IU/l, showing agranulocytosis
      and drug-induced hepatitis. The chemotherapy was immediately withdrawn and she
      was admitted to our hospital on the next day. Glycyrrhizin derivative (SNMC) 40
      ml was injected for 5 days, and WBC recovered, and AST and ALT also became
      normal. CASE 4: A 60-year-old man was admitted to our hospital on March 11, 1981
      because pulmonary tuberculosis had recurred. He had been treated with SM, PAS and
      INH in 1973 for pulmonary tuberculosis. On admission examination of blood count
      and blood chemistry were normal. Treatment with RFP, INH and SM was started on
      March 11. He stopped out from the hospital on April 17, but in a few days he
      returned back with sore throat, lower lip swelling and gingival bleeding. Blood
      cell count on April 24 showed pancytopenia with RBC 226, Hb 7.5, WBC 800 (Ly 96%,
      Eos 4%) and Plt 10,000/microliter. The bone-marrow showed NCC (nuceated cell
      count) of 5,500, and megakaryocyte 0. Thereafter ground glass appearance shadows
      were seen on the whole lung field, and he died May 26. Autopsy showed generalized
      aspergillosis. It was strongly suspected that either of RFP, INH or SM was
      responsible for his pancytopenia. We collected another 10 cases of
      agranulocytosis due to anti-tuberculosis drugs in the world wide literature, and
      found men/women ratio 5/8 (in one case gender was not known), the duration of
      chemotherapy before appearance of agranulocytosis 1-3 months, no change in the
      lymphocyte count of the peripheral blood, and the accompanying of another
      allergic signs such as skin eruption, blood eosinophilia or drug-induced
      hepatitis in some cases, and these findings suggest that the mechanism of
      agranulocytosis due to anti-tuberculosis drugs was allergic in nature.

PMID- 14672047
TI  - [An adult case of hypoplasia of the left lung disclosed by pneumonectomy for
      pulmonary M. avium complex infection associated with intractable pneumothorax].
AB  - A case of W-P-W syndrome complicated with pulmonary hypoplasia disclosed by
      pneumonectomy for pulmonary Mycobacterium avium complex infection associated with
      intractable pneumothorax was reported. A male patient aged 52 years consulted our
      clinic with chief complaints of cough and abnormal shadows on his chest
      radiogram, which was consistent with mycobacteriosis on his left lung. MAC
      infection was soon confirmed by sputum examination and he was treated with RFP,
      EB, INH combined with CAM. In spite of the chemotherapy, sputum examination of
      the patient remained positive. Furthermore, eleven months after initiating the
      treatment, an intractable pneumothorax concurrent with a large dead space at the
      left lower lung field was consistently observed on his chest radiogram.
      Therefore, he was first treated by video assisted thoracoscopic surgery, but soon
      relapsed which led to tention pneumothorax gradually. Consequently, a left
      pneumonectomy had to be performed and the following developmental abnormalities
      combined with pathological changes caused by MAC infection were disclosed:
      concerning the upper lobe, defect of lingula, formation of a peripheral type of
      congenital air-filled parenchymal cyst measuring 5 x 6 cm in S3, and atelectatic
      induration caused by MAC infection on the remaining part of the upper lobe where
      strong adhesion was seen between the chest wall and the lung. Concerning the
      lower lobe, congenital shortening of visceral pleura, mainly mediastinal surface,
      causing marked deformity of the lower lobe with elevation of margo inferior. This
      created a large dead space between the lower lobe and diaphragma, and formation
      of a walnut-sized nest of atelectatic induration caused by MAC infection in S6.
      The patient's post-operative clinical course was uneventful and his arterial
      blood gas was elevated from 76 torr to 99.2 torr. He was discharged three weeks
      after the operation. Several controversial issues relating to this case were
      discussed; the predisposition existing on the hypoplastic lung to MAC infection,
      the possible reason why the congenital pulmonary cyst was not involved in MAC
      infection, the location of perforation of the upper lobe that caused intractable
      pneumothorax, and the difficulty in diagnosing congenital air-filled bullous
      parenchymal cyst by current conventional chest radiogram.

PMID- 14672046
TI  - [A survey on the onset of tuberculosis in nursing homes].
AB  - PURPOSE: To obtain the informations how to promote early detection and prevention
      of nosocomial infection of tuberculosis in nursing homes for the elderly.
      SUBJECT: Fifteen elderly patients who developed tuberculosis from 1998 to 2002 at
      nursing homes within a certain health center jurisdiction area which has a total
      of 23 nursing homes were investigated. METHOD: We collected informations on these
      15 patients concerning the clinical conditions, details of contact examinations
      and status of chemoprophylaxis by using TB registration card in the health center
      and interviewing with the members of staff of the nursing homes and hospitals,
      and case conferences conducted at the health center. RESULTS: Four patients died
      within 10 days after the diagnosis due to the delay in referring them to doctors.
      The most common symptoms leading to the detection was fever, followed by cough.
      DISCUSSION: Early diagnosis is the key to prevent early death and nosocomial
      infection of tuberculosis in nursing homes. A similar study will be useful at
      each health center or region to improve the tuberculosis control in nursing
      homes. CONCLUSION: Tuberculosis control programs in nursing homes should be
      strengthened. The staff of nursing homes should be trained for closer
      observations of the elderly about their health conditions such as fever and
      cough, and their early reference to physicians when such symptoms were observed.
      Two step tuberculin skin tests to the staff is also important for the contact
      investigations.

PMID- 14672048
TI  - Mycobacterium kansasii, species or complex? Biomolecular and epidemiological
      insights.
AB  - Mycobacterium kansasii is one of the best known nontuberculous mycobacteria and
      large awareness exists about its involvement in diseases both of immunocompetent
      and immunocompromised patients. Two phenotypic variants within this species,
      which differ for the virulence in guinea pig too, have been detected since 1962.
      It was however following recent progress in genetic studies that a large
      variability emerged. Major contributions to the disclosure of such findings came
      from the DNA probes hybridization, the nucleotide sequencing of 16 rDNA and
      internal transcribed spacer (ITS), and from the analyses of repetitive DNA
      sequences polymorphism. At present five subtypes of M. kansasii are recognized,
      defined by the ITS sequence and by the polymorphism revealed by different
      restriction enzyme technologies. Such variants differ from the epidemiological
      point of view too, with type i being isolated from humans, type ii both from
      humans and environment, and types iii, iv and v, from the environment only. A
      revision of the present taxonomic status of M. kansasii and its splitting into
      different species or subspecies seems nowadays necessary.

PMID- 14672049
TI  - [Pneumoconiosis and mycobacterial infection].
AB  - This symposium was organized to provide recent informations concerning
      pneumoconiosis and mycobacterial diseases in Japan. Pneumoconiotic workers have
      been decreasing in number and in severity because of change in industrial
      structure and improvement of occupational health measures. But radiological
      figures of dust exposed worker are going to be complex and be difficult for
      diagnosis due to aging, smoking and of complicated respiratory and non
      respiratory diseases. Major complications such as pulmonary tuberculosis and
      tuberculous pleurisy are decreasing but non-tuberculous mycobacterial infections
      have become common among dust exposed workers. Dr. Katsuhiro Suzuki (National
      Kinki-Chuo Hospital) reported pulmonary tuberculosis complicated with
      pneumoconiosis. A few reports regarding tuberculosis with pneumoconiosis have
      been published in recent years, particularly in Japan. Thus, clinical
      characteristics of the cases in our hospital between 1998 and 2003 were
      summarized here. There were 22 such patients, who consisted of 21 men and one
      woman and were 49 to 91 years old. There were 19 cases with silicosis, two cases
      with asbestosis, and one case with siderosis. Bilateral and cavitary lesions in a
      chest XP were revealed in 82% and 29% of the cases, respectively. Standard
      chemotherapeutic regimens consisted of three or four drugs with a prolonged
      period were found to be as effective as that for healthy subjects, judging from
      the sputum conversion rate after 8 week treatment. Dr. Toshiyuki Yamauchi (Keihai
      Rosai Hospital) reported, based on autopsy findings, trends in combined-type
      tuberculosis accompanying pneumoconiosis. The study period was divided into first
      (1963-1980) and second (1981-2000) stages based on year of patients death. To
      assess the therapeutic efficacy of antituberculosis agents, patients with
      combined-type tuberculosis were pathologically divided into those with active
      tuberculosis and those with inactive tuberculosis. The incidence of active
      tuberculosis during the second stage was significantly lower than that during the
      first stage. In both first and second stages, the average age of death for
      patients with inactive tuberculosis was older than that for those with active
      tuberculosis. It was shown that active combined-type tuberculosis was resistant
      to antituberculosis therapy and the prognosis of those patients tends to be poor.
      But for all patients with active and inactive combined-type tuberculosis, the
      average age of death was comparable to that of patients without tuberculosis in
      each stage. The results indicated that the antituberculosis agents were effective
      to combined-type tuberculosis. Dr. Kiyonobu Kimura (Iwamizawa Rosai Hospital)
      carried out retrospective studies on some clinico-epidemiologic problems in the
      cases accumulated in his hospital during the past 49 years. Since his cases
      consist of various different pathological changes, he has adopted the term
      "pneumoconiosis complicated with pulmonary tuberculosis" instead of silico
      tuberculosis. The results were summarized as follows: (1) The rates of active
      pulmonary tuberculosis out of 1051 total dead cases were 43.8% (28/64) from 1955
      to 1964, 28.8% (62/215) from 1965 to 1974, 24.7% (93/376) from 1975 to 1984, and
      10.1% (40/396) from 1985 to 1994. (2) The rates of those who died of pulmonary
      tuberculosis were 17.2% (11/64) from 1955 to 1964, 9.3% (20/215) from 1965 to
      1974, 1.9% (7/376) from 1975 to 1984, and 3.3% (13/396) from 1985 to 1994,
      respectively. (3) The average age of death of pulmonary tuberculosis has become
      older and is not significantly different from that of pneumoconiosis patients who
      died of other cause. (4) The rate of sputum negative conversion was only 9.1%
      (3/33) during the first 10 years (from 1955 to 1964). On the other hand, 95%
      (21/22) in the recent 9 years (from 1993 to 2002). (5) Out of the 104 autopsy
      cases in whom pneumoconiosis and tuberculosis were diagnosed pathologically, 64
      cases were combined form of tuberculosis, and other 40 cases were complicated
      form of tuberculosis. Dr. Hiroki Morita (Asahi Rosai Hospital) studied the
      nontuberculous mycobacteria (NTM) in the patients with pneumoconiosis and the
      clinical courses of the 4 types of pneumoconiosis complicated with NTM pulmonary
      disease. NTM were detected in the 73 (29%) of 252 pneumoconiosis. The 14 species
      (M. gordonae, M. avium, M. terrae, M. fortuitum, M. nonchromogenicum, M.
      peregrinum, M. intracellulare, M. szulgai, M. abscessus, M. simiae, M. chelonae,
      M. scrofulaceum, M. xenopi, M. triviale) were identified. In the long-term follow
      up study of the pneumoconiosis patients complicated by NTM pulmonary disease, it
      was very difficult to catch the onset of NTM pulmonary disease because the
      clinical signs and symptoms were nonspecific and the radiographic findings moved
      very slowly. Dr. Mitsunori Sakatani (National Kinki-Chuo Hospital) reviewed the
      laws related safety and health for dust exposed workers, pneumoconiosis and
      tuberculosis, and he pointed out importance for prevention, diagnosis, treatment
      and compensation.

PMID- 14672050
TI  - [Tuberculosis in compromised hosts].
AB  - Recent development of tuberculosis in Japan tends to converge on a specific high
      risk group. The proportion of tuberculosis developing particularly from the
      compromised hosts in the high risk group is especially high. At this symposium,
      therefore, we took up diabetes mellitus, gastrectomy, dialysis, AIDS and the
      elderly for discussion. Many new findings and useful reports for practical
      medical treatment are submitted; why these compromised hosts are predisposed to
      tuberculosis, tuberculosis diagnostic and remedial notes of those compromised
      hosts etc. It is an important question for the future to study how to prevent
      tuberculosis from these compromised hosts. 1. Tuberculosis in diabetes mellitus:
      aggravation and its immunological mechanism: Kazuyoshi KAWAKAMI (Department of
      Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty
      of Medicine, University of the Ryukyus). It has been well documented that
      diabetes mellitus (DM) is a major aggravating factor in tuberculosis. The onset
      of this disease is more frequent in DM patients than in individuals with any
      underlying diseases. However, the precise mechanism of this finding remains to be
      fully understood. Earlier studies reported that the migration, phagocytosis and
      bactericidal activity of neutrophils are all impaired in DM patients, which is
      related to their reduced host defense to infection with extracellular bacteria,
      such as S. aureus and E. colli. Host defense to mycobacterial infection is
      largely mediated by cellular immunity, and Th1-related cytokines, such as IFN
      gamma and IL-12, play a central role in this response. It is reported that serum
      level of these cytokines and their production by peripheral blood mononuclear
      cells (PBMC) are reduced in tuberculosis patients with DM, and this is supposed
      to be involved in the high incidence of tuberculosis in DM. Our study observed
      similar findings and furthermore indicated that IFN-gamma and IL-12 production by
      BCG-stimulated PBMC was lower in poorly-controlled DM patients than that in well
      controlled DM patients and healthy subjects. Thus, these clinical data suggest
      that the high incidence of tuberculosis in DM patients is due to the impaired
      production of Th1-related cytokines. However, direct evidences to prove this
      possibility remain to be obtained. In 1980, Saiki and co-workers reported that
      host defense and delayed-type hypersensitivity response to M. tuberculosis was
      hampered in a mouse DM model established by injecting streptozotocin (Infect
      Immun. 1980; 28: 127-131). We followed their investigation with the similar
      observations. Interestingly, levels of IFN-gamma and IL-12 in serum, lung, liver
      and spleen after infection were significantly reduced in DM mice when compared
      with those in control mice. Considered collectively, these results strongly
      suggest that the reduced production of Th1-related cytokines leads to the
      susceptibility of DM to mycobacterial infection. However, it remains to be
      understood how DM hampers the synthesis of Th1-related cytokines. In our
      preliminary study, the production of these cytokines by PBMC from DM patients and
      healthy subjects was not affected under a high glucose condition. Thus, it is not
      likely that the increased level of glucose directly suppresses the cell-mediated
      immune responses. Further investigations are needed to make these points clear.
      2. A study of gastrectomy cases in pulmonary tuberculosis patients: Takenori YAGI
      (Division of Thoracic Disease, National Chiba-Higashi Hospital). Patients who
      have undergone gastric resection are considered at increased risk of developing
      pulmonary tuberculosis. I have investigated the role played by gastrectomy in
      giving rise to pulmonary tuberculosis. Of 654 pulmonary tuberculosis patients
      admitted to National Chiba-Higashi Hospital from January 1999 to December 2001,
      55 patients (31-84 years old, mean 63.5 +/- 12.5 years, 48 males and 7 females)
      had the history of gastric resection. The incidence of gastrectomy among patients
      with pulmonary tuberculosis was 8.4 percent. The mean age of gastric resection
      was 50.2 +/- 16.6 years, and the mean interval from gastrectomy to pulmonary
      tuberculosis was 13.6 +/- 11.0 years. On admission to our hospital, 34 out of 55
      cases were smear positive by sputum examination for acid-fast bacilli and 39
      cases had cavitary lesions on chest X-ray. Gastrectomy was done due to carcinoma
      of the stomach in 31 cases, gastric and/or duodenal ulcer in 21 cases,
      adenomatous polyp in two cases, and accidental injury in one case. 52 patients
      improved, but three cases died due to pulmonary tuberculosis. No one had
      recurrence of carcinoma of the stomach. Body weight, Body Mass Index, Prognostic
      Nutritional Index (PNI; 10x serum albumin concentration +0.005 x peripheral
      lymphocyte count) which was proposed by Onodera, serum albumin level and serum
      total cholesterol level were lower in the gastrectomy group than in the non
      gastrectomy group. I calculated the odds of tuberculosis among gastrectomy
      patients to be 3.8 times that of appropriate controls. This study confirms that
      gastrectomy is one of the risk factor(s) of tuberculosis. However, whether
      gastrectomy in itself is a risk factor or whether it is secondarily associated
      with another risk factor such as underweight status and/or inadequate nutrition
      following surgery remains unclear. 3. Immunodefficiency and tuberculosis in
      dialysis patients: Hajime INAMOTO (Division of Dialysis, Keio University School
      of Medicine). The patients who have renal insufficiency is fatal, but they can
      live much longer by dialysis. The number of lymphocytes of the patients whose
      serum creatinine was 10 mg/dl or more has decreased to about 50% of the people
      who have normal kidney. When the lymphocyte was cultured after it was stimulated
      with PHA, the DNA synthesis of the patients' lymphocyte was much lower than that
      of the modest people's. In the dialysis food, the nutrient such as vitamins,
      minerals, etc. were lacked. The density of the serum albumin of the dialysis
      patient has decreased. Many of them were thin when their BMI was examined. The
      size of the patients' erythema by the tuberculin test has become small. There
      were many patients receiving dialysis with erythema but no induration. It means
      that the delayed skin reaction specific to Mycobacterium tuberculosis has
      decreased among the dialysis patients. The morbidity rate, the mortality rate and
      the prevalence of tuberculosis was much higher than the general population. The
      anamnesis of tuberculosis was also high. Most of those tuberculosis patients
      appear the disease from the period immediately before the beginning of dialysis
      to one year after that. That is also the period that patients' number of
      peripheral blood lymphocyte decreased and the tuberculin reaction positivity rate
      fell sharply. During the dialysis patients, pulmonary tuberculosis with cavities
      was minority and extrapulmonary tuberculosis and miliary tuberculosis were
      remarkably many. People with large reaction against the tuberculin test were
      better prognosis than those with smaller reaction. It was thought that anorexia,
      weakening, and a weight decrease were seen when the immunity decreased. At the
      end stage of renal failure, kidney shrink, vitamin D activation becomes
      difficult, and the low calcium blood syndrome appears. The calcification of
      tuberculoma is absorbed, soft tuberculoma becomes baring, the caseation abscess
      melts, and the endogenous infection occurs. The cell immunity has decreased, and
      tuberculosis attacks. It might be such circumstances that tuberculosis happen
      frequently at the dialysis introduction period. There are a lot of cases that the
      caseation necrosis is a little, and the formation of tuberculoma is bad in the
      pathology opinion. Due to the decrease in the cell immunity, cavities are not
      formed easily. It is easy to stay in the leaching lesion so that anti
      tuberculosis drugs are much effective, and the patients recover easily. However,
      if the treatment is delayed, it is fatally because hematogenous metastasis are
      easy to occur and become miliary tuberculosis. 4. AIDS and tuberculosis: Hideaki
      NAGAI (Department of Respiratory Diseases, National Tokyo Hospital). With AIDS
      patients with tuberculosis, there are the following problems on the treatment.
      (1) The adverse reactions by antituberculosis drugs tend to occur in AIDS
      patients. Eleven of 33 AIDS patients with tuberculosis had the adverse reactions
      (skin rash, fever, liver dysfunction) considered to be due to antituberculosis
      drugs. It is a very large burden for the HIV infected persons to take
      simultaneously antituberculosis drugs, medicines for opportunistic infections,
      and anti-HIV medicines. Since many medicines are taken, it is difficult to
      determine which drug is the cause once an adverse reaction occurs and all
      medicines should be often stopped. (2) The combined use with rifampicin (RFP) is
      difficult for the protease inhibitors and nonnuclear acid reverse transcriptase
      inhibitors. RFP induces cytochrome P-450 in liver, accelerates the metabolism of
      some concomitant drug agents, and reduces blood concentration them remarkably.
      When starting the two above-mentioned medicines during tuberculosis treatment,
      RFP should be changed to rifabutin (RFB) which has less induction of P-450 than
      RFP. However, some procedures are required for acquisition of RFB and it is a
      little complicated in Japan. CDC mentioned the combined use with RFP and
      efavirenz (EFV) is possible. So, the treatment with EFV and RFP is recently
      chosen. However, the monitor of the blood concentration of EFV is required, and
      the dose of EFV should be increased if it is a low value. (3) When a highly
      active antiretroviral therapy (HAART) is given to AIDS patients with
      tuberculosis, transient worsening of tuberculosis may develop after about two
      weeks. (ABSTRACT TRUNCATED)

PMID- 14672051
TI  - Talking about sex in HIV-related counseling and health care settings.

PMID- 14672052
TI  - Talking about HIV prevention without demonizing sex.

PMID- 14672053
TI  - Connecting the dots: integrating HIV and substance abuse.

PMID- 14672054
TI  - Methamphetamine and club drug use and HIV.

PMID- 14672055
TI  - New guidelines: clinicians should incorporate HIV prevention into ongoing care of
      patients.

PMID- 14672056
TI  - Managing HIV/HBV coinfection can challenge some clinicians.

PMID- 14672057
TI  - Anatomy of an accident: lessons learned after a needlestick.

PMID- 14672058
TI  - Women, men and microbicides.

PMID- 14672059
TI  - The international epidemiologist. A talk with Zena Stein. Interview by Jen Curry.

PMID- 14672060
TI  - Women, power and microbicides.

PMID- 14672061
TI  - Building a microbicides advocacy campaign.

PMID- 14672063
TI  - FDA: global citizen.

PMID- 14672064
TI  - The role of housing in better care outcomes for people with AIDS.

PMID- 14672062
TI  - Kaletra goes it alone.

PMID- 14672065
TI  - Community housing and AIDS.

PMID- 14672066
TI  - Clinical conversations: brief psychotherapy training and HIV.

PMID- 14672068
TI  - GALEN moves forward.

PMID- 14672067
TI  - The clinical conversation with gay men: a new experience of relating.

PMID- 14672069
TI  - BMS issues PK notice regarding ATV + TDF.

PMID- 14672070
TI  - 20 years of HIV science: setbacks and activism.

PMID- 14672071
TI  - US revises adult/adolescent antiretroviral therapy guidelines.

PMID- 14672072
TI  - Back to basics...making HIV testing routine.

PMID- 14672073
TI  - UK health service gets thumbs up in independent analysis. Mid-term appraisal of
      government's quality agenda finds reforms have led to improvements in health
      care.

PMID- 14672074
TI  - AIDS campaign signals new WHO priorities and approach. Lee promises to focus on
      real targets and improving WHO's effectiveness.

PMID- 14672075
TI  - Report highlights hazard of smoke from indoor fires.

PMID- 14672076
TI  - Ominous start to US influenza season.

PMID- 14672077
TI  - Kyrgyz medical academy implicated in illegal body trade.

PMID- 14672078
TI  - Italian GPs strike over long-awaited contract.

PMID- 14672079
TI  - USA-Morocco deal may extend drug patents to 30 years.

PMID- 14672080
TI  - Launch of AIDS fund for Red Cross staff.

PMID- 14672081
TI  - Pacific nations lead the way in fighting lymphatic filariasis.   Region aims to
      eliminate.

PMID- 14672082
TI  - Notification that new names and new combinations have appeared in volume 53, part
      4, of the IJSEM.

PMID- 14672083
TI  - Effects of sevoflurane and isoflurane on the ratio of cerebral blood
      flow/metabolic rate for oxygen in neurosurgery.
AB  - PURPOSE: To examine the changes in cerebral blood flow (CBF) equivalent (CBF
      divided by cerebral metabolic rate for oxygen) during craniotomy under isoflurane
      and sevoflurane anesthesia in patients with intracranial disorders. METHODS: In
      16 neurosurgical patients (8 anesthetized with isoflurane and 8 with
      sevolflurane), the CBF equivalent was measured while the end-tidal concentration
      of the selected volatile anesthetic was maintained at 0.5 and 1.0 minimum
      alveolar concentration (MAC) before surgery, and then 1.0 MAC during surgery,
      which lasted more than 4 hr. RESULTS: There was no significant difference in CBF
      equivalent at 0.5 MAC between isoflurane (20 +/- 4ml blood.ml oxygen) groups.
      With increasing anesthetic depth from 0.5 to 1.0 MAC, the CBF equivalent
      significantly (P<0.5) increased in both groups (22 +/- 7 and 21 +/- 5,
      respectively). At 1.0 MAC during operation, the CBF equivalent with both
      anesthetics was maintained with minimal fluctuation for 4h. There were no
      significant differences in the average value of the CBF equivalent during a 4-h
      period at 1.0 MAC between the isoflurane (23 +/- 5) and the sevoflurane (20 +/-
      4) groups. CONCLUSION: Deepening anesthesia from 0.5 to 1.0 MAC was maintained
      with no difference between the two agents during 4h of neurosurgery.

PMID- 14672084
TI  - Requirements for submission of labeling for human prescription drugs and
      biologics in electronic format. Final rule.
AB  - The Food and Drug Administration (FDA) is amending its regulations governing the
      format in which certain labeling is required to be submitted for review with new
      drug applications (NDAs), certain biological license applications (BLAs),
      abbreviated new drug applications (ANDAs), supplements, and annual reports. The
      final rule requires that certain labeling content be submitted electronically in
      a form that FDA can process, review, and archive. Submitting the content of
      labeling in electronic format will simplify the drug labeling review process and
      speed up the approval of labeling changes.

PMID- 14672085
TI  - The use of rice hulls for sustainable control of NOx emissions in deep space
      missions.
AB  - The use of the activated carbon produced from rice hulls to control NOx emissions
      for future deep space missions has been demonstrated. The optimal carbonization
      temperature range was found to be between 600 and 750 degrees C. A burnoff of
      61.8% was found at 700 degrees C in pyrolysis and 750 degrees C in activation.
      The BET surface area of the activated carbon from rice hulls was determined to be
      172 m2/g when prepared at 700 degrees C. The presence of oxygen in flue gas is
      essential for effective adsorption of NO by activated carbon. On the contrary,
      water vapor inhibits the adsorption efficiency of NO. Consequently, water vapor
      in flue gas should be removed by drying agents before adsorption to ensure high
      NO adsorption efficiency. All of the NO in the flue gas was removed for more than
      1.5 h when 10% oxygen was present and the ratio of the carbon weight to the flue
      gas flow rate (W/F) was 15.4 g min/L. Reduction of the adsorbed NO to form N2
      could be effectively accomplished under anaerobic conditions at 550 degrees C.
      The adsorption capacity of NO on the activated carbon was found to be 5.02 mg of
      NO/g of carbon. The loss of carbon mass was determined to be about 0.16% of the
      activated carbon per cycle of regeneration if the regeneration occurred when the
      NO in the flue gas after the carbon bed reached 4.8 ppm, the space maximum
      allowable concentration. The reduction of the adsorbed NO also regenerated the
      activated carbon, and the regenerated activated carbon exhibited an improved NO
      adsorption efficiency.

PMID- 14672086
TI  - Method for the control of NOx emissions in long-range space travel.
AB  - The wheat straw, an inedible biomass that can be continuously produced in a space
      vehicle has been used to produce activated carbon for effective control of NOx
      emissions from the incineration of wastes. The optimal carbonization temperature
      of wheat straw was found to be around 600 degrees C when a burnoff of 67% was
      observed. The BET surface area of the activated carbon produced from the wheat
      straw reached as high as 300 m2/g. The presence of oxygen in flue gas is
      essential for effective adsorption of NO by activated carbon. On the contrary,
      water vapor inhibits the adsorption efficiency of NO. Consequently, water vapor
      in flue gas should be removed by drying agents before adsorption to ensure high
      NO adsorption efficiency. All of the NO in the flue gas was removed for more than
      2 h by the activated carbons when 10% oxygen was present and the ratio of carbon
      weight to the flue gas flow rate (W/F) was 30 g min/L, with a contact time of
      10.2 s. All of NO was reduced to N2 by the activated carbon at 450 degrees C with
      a W/F ratio of 15 g min/L and a contact time of 5.1 s. Reduction of the adsorbed
      NO also regenerated the activated carbon, and the regenerated activated carbon
      exhibited an improved NO adsorption efficiency. However, the reduction of the
      adsorbed NO resulted in a loss of carbon which was determined to be about 0.99%
      of the activated carbon per cycle of regeneration. The sufficiency of the amount
      of wheat straw in providing the activated carbon based on a six-person crew, such
      as the mission planned for Mars, has been determined. This novel approach for the
      control of NOx emissions is sustainable in a closed system such as the case in
      space travel. It is simple to operate and is functional under microgravity
      environment.

PMID- 14672087
TI  - Injury risk in men's university football.

PMID- 14672088
TI  - Home exercise for knee pain and knee osteoarthritis.

PMID- 14672089
TI  - Physical activity and risk of upper respiratory tract infections.

PMID- 14672090
TI  - Recreational physical activity and endometrioma risk.

PMID- 14672091
TI  - [Treating type 2 diabetes: theory and practice].

PMID- 14672092
TI  - [New therapies in the treatment of diabetes!].

PMID- 14672093
TI  - Accelerated development of viral inhibitor Thirovir for HIV.

PMID- 14672094
TI  - Population data of four X-chromosome markers in Tuscany, and their use in a
      deficiency paternity case.
AB  - Four X-chromosome markers (DXS101, HPRTB, DXS8377, and STRX-1) were typed in a
      population sample from Tuscany, Italy, using a single amplification reaction.
      Resolution of a deficiency paternity case involving two women (either they were
      half-sisters or non-relatives) was made possible by typing these marker in
      addition to 16 conventional autosomal markers.

PMID- 14672095
TI  - Editorial. Methodological advances in cross-cultural study of mental health:
      setting new standards.

PMID- 14672096
TI  - Optically stimulated luminescence and thermoluminescence efficiencies for high
      energy heavy charged particle irradiation in Al2O3:C.
AB  - The thermally and optically stimulated luminescence (TL and OSL) response to high
      energy heavy-charged particles (HCPs) was investigated for two types of Al2O3:C
      luminescence dosimeters. The OSL signal was measured in both continuous-wave (CW)
      and pulsed mode. The efficiencies of the HCPs at producing TL or OSL, relative to
      gamma radiation, were obtained using four different HCPs beams (150 MeV/u 4He,
      400 MeV/u 12C, 490 MeV/u 28Si, and 500 MeV/u 56Fe). The efficiencies were
      determined as a function of the HCP linear energy transfer (LET). It was observed
      that the efficiency depends on the type of detector, measurement technique, and
      the choice of signal. Additionally, it is shown that the shape of the CW-OSL
      decay curve from Al2O3:C depends on the type of radiation, and, in principle,
      this can be used to extract information concerning the LET of an unknown
      radiation field. The response of the dosimeters to low-LET radiation was also
      investigated for doses in the range from about 1-1000 Gy. These data were used to
      explain the different efficiency values obtained for the different materials and
      techniques, as well as the LET dependence of the CW-OSL decay curve shape.

PMID- 14672098
TI  - Microvascular blood flow fluctuations during tilt table induced syncope.
AB  - Aim of this study is to investigate the changes, in the frequency domain, of
      microvasculature blood flow (BF) occurring in neurally mediated syncope. We
      studied 20 patients with history of recurrent syncope and 10 control subjects.
      Peripheral BF was measured (laser Doppler technique) in the palmar region (PBF)
      and the manubrium sterni (SBF), together with ECG, respiration activity (RA) and
      blood pressure (BP), at rest (5 minute) and during 70 degrees head-up tilt test.
      SBF and PBF appear to be characterized by oscillations around 0.16 Hz (0.15-0.19
      Hz), that do not have correspondence in the other cardiovascular variability
      signals. Mean BF was not significantly altered in tilt negative, control and tilt
      positive groups (11 patients) during tilt. In the tilt positive group a decrease
      of mean PBF and SBF and an increase of the oscillation frequency of PBF and SBF
      was observed in close proximity of the development of symptoms.

PMID- 14672097
TI  - A semi-automatic method for left ventricle volume estimate: an in vivo validation
      study.
AB  - This study aims to the validation of the left ventricular (LV) volume estimates
      obtained by processing volumetric data utilizing a segmentation model based on
      level set technique. The validation has been performed by comparing real-time
      volumetric echo data (RT3DE) and magnetic resonance (MRI) data. A validation
      protocol has been defined. The validation protocol was applied to twenty-four
      estimates (range 61-467 ml) obtained from normal and pathologic subjects, which
      underwent both RT3DE and MRI. A statistical analysis was performed on each
      estimate and on clinical parameters as stroke volume (SV) and ejection fraction
      (EF). Assuming MRI estimates (x) as a reference, an excellent correlation was
      found with volume measured by utilizing the segmentation procedure (y) (y=0.89x +
      13.78, r=0.98). The mean error on SV was 8 ml and the mean error on EF was 2%.
      This study demonstrated that the segmentation technique is reliably applicable on
      human hearts in clinical practice.

PMID- 14672099
TI  - Loudness adaptation: fact or artifact?
AB  - In the present study, the authors tested the hypothesis that contrast effects
      confound the Ipsilateral Comparison Paradigm (ICP). Bidirectional referents were
      used in which base tones of 50 or 70 dB alternated with referents of greater or
      lesser intensity in a 3.5-min listening period. The contrast hypothesis leads to
      the expectation that the bidirectional referents would produce opposing effects
      that should nullify time-based loudness changes in the common base tone. Contrary
      to that expectation, base-tone loudness declined significantly over time in the
      context of the bidirectional referents, and the loudness of the referents also
      declined significantly over time. Thus, the results of the study testified to the
      validity of the ICP as a contrast-free measure of broad-based loudness
      adaptation.

PMID- 14672100
TI  - Limits of the retrieval-inhibition construct: list segregation in directed
      forgetting.
AB  - The authors hypothesized that retrieval inhibition in list method directed
      forgetting could be improved by presenting a task that maximized the segregation
      step of the retrieval-inhibition process. In Experiment 1, they presented lists
      of semantically related words in a list method directed-forgetting task to
      maximize retrieval inhibition. Contrary to predictions, this manipulation
      eliminated the directed-forgetting effect. The authors further investigated the
      results of Experiment 1 in Experiments 2 and 3 by manipulating recall
      instructions and by presenting lists that contained both a categorized and an
      unrelated list-half. They found directed-forgetting effects for semantically
      related word lists when participants were asked to recall only the TBR (to-be
      remembered) items but not when participants were asked to recall both the TBF (to
      be-forgotten) and TBR items. They also found that directed-forgetting effects
      were not produced when categorized items were presented in the 1st list.

PMID- 14672101
TI  - Directed forgetting of related words: evidence for the inefficient inhibition
      hypothesis.
AB  - Fifth-grade children and college students were asked to remember some words and
      to forget others in an item-cued-directed-forgetting task. Taxonomically related
      pairs of words and control pairs that were unrelated in meaning were used as
      stimuli. Children found it more difficult than did adults to ignore forget-cued
      words that followed associatively related words that were remember-cued. The
      results provide support for D. F. Bjorklund and K. K. Harnishfeger's (1990)
      inefficient inhibition hypothesis (i.e., that the efficiency of inhibitory
      mechanisms improves as children develop). The results also suggest that the
      inhibition is occurring primarily in the early stages of processing.

PMID- 14672102
TI  - Limitations of the mnemonic-keyword method.
AB  - The effectiveness of the mnemonic-keyword method was investigated in 4
      experiments in which participants were required to learn the 1st-language (L1,
      Spanish) equivalents of a list of 30 2nd-language words (L2, Latin). Experiments
      1 (adolescents) and 2 (adults) were designed to assess whether the keyword method
      was more effective than the rote method; the researcher supplied the keyword, and
      the participants were allowed to pace themselves through the list. Experiments 3
      (adolescents) and 4 (adults) were similar to Experiments 1 and 2 except that the
      participants were also supplied with a drawing that illustrated the relationship
      between the keyword and the L1 target word. All the experiments were performed
      with groups of participants in their classrooms (i.e., not in a laboratory
      context). In all experiments, the rote method was significantly more effective
      than was the keyword method.

PMID- 14672104
TI  - What does a "superstitious" person believe? Impressions of participants.
AB  - The questions in surveys in which superstitious belief is examined are based on
      the researcher or researchers' definitions of superstition and not on
      participants' definitions. In the present study, 170 undergraduates filled out 2
      surveys. In the 1st survey, they were asked to rate 28 possible beliefs of a
      fictitious person described as "superstitious." In the 2nd survey, they were
      asked to rate their own level of belief for the same items. An analysis revealed
      several different factors describing different types of beliefs held by the
      fictitious person. Ratings for the fictitious person were greatest for socially
      transmitted beliefs (e.g., black cats, rabbits' feet) or idiosyncratic rituals
      related to luck and chance, followed by belief in the paranormal (e.g., ghosts),
      spiritualism (e.g., reincarnation), or psi (e.g., telepathy). Religious beliefs
      were rated as not being descriptive of the fictitious superstitious person.
      However, an analysis of the participants' own beliefs revealed that those with
      higher levels of religious belief also tended to be superstitious and believed in
      the paranormal.

PMID- 14672103
TI  - Controlling for causally relevant third variables.
AB  - In 3 experiments, the authors tested the conditions under which 3rd variables are
      controlled for in making causal judgments. The authors hypothesized that 3rd
      variables are controlled for when the 3rd variables are themselves perceived as
      causal. In Experiment 1, the participants predicted test performance after seeing
      information about wearing a lucky garment, taking a test-preparation course, and
      staying up late. The course (perceived as more causally relevant) was controlled
      for more than was the garment (perceived as less causally relevant) in assessing
      the effectiveness of staying up late. In Experiments 2 and 3, to obviate the many
      alternative accounts that arise from the realistic cover story of Experiment 1,
      participants predicted flowers' blooming after the presentation or
      nonpresentation of liquids. When one liquid was trained as causal, it was
      controlled for more in judging another liquid than when it was trained as
      neutral. Overall, stimuli perceived as causal were controlled for more when
      judging other stimuli. The authors concluded that the effect of perceived causal
      relevance on causal conditionalizing is real and normatively reasonable.

PMID- 14672105
TI  - The CS-preexposure effect in conditioned taste-aversion learning in golden
      hamsters.
AB  - In Experiment 1, golden hamsters were injected with either 0.9% saline or the
      nausea-inducing agent, lithium chloride (LiCL), immediately after consuming a
      flavored diet that was either novel or familiar. The LiCl-induced aversion was
      strong in hamsters for which the flavored diet was novel, but no significant
      aversion was observed in hamsters that were familiar with the flavored diet. In
      Experiment 2, the strength of the LiCl-induced aversion was related inversely to
      the amount of conditioned-stimulus (CS) preexposure and directly to the duration
      of the preexposure-conditioning interval. Thus, although some previous
      researchers have suggested that hamsters may not demonstrate the CS-preexposure
      effect in a conditioned taste-aversion paradigm, they clearly did so under the
      conditions of the present experiments, and moreover, the characteristics of the
      CS-preexposure effect in hamsters were generally similar to those observed in
      rats.

PMID- 14672107
TI  - Men with prostate cancer: making decisions about complementary/alternative
      medicine.
AB  - PURPOSE: The purpose of this study was to explore prostate cancer patients
      'perceptions, feelings, ideas, and experiences regarding making decisions to use
      (or not use) complementary/alternative medicine (CAM). METHODS: Five focus groups
      were conducted with 29 men diagnosed with prostate cancer. Content analysis of
      the verbatim transcripts was used to identify key themes in the data. FINDINGS:
      Decision making about CAM treatments appears to depend on both fixed (e.g.,
      disease characteristics, demographic characteristics, and medical history) and
      flexible (e.g., perceptions of CAM and conventional medicine, experiences with
      the health care system and health care practitioners, and perceptions about the
      need for control or action) decision factors. CONCLUSIONS: The participants in
      this study appeared more likely to be "pushed" toward using CAM by negative
      experiences with the health care system than to be "pulled" toward CAM by
      perceptions about its safety or congruence with their beliefs about health and
      illness.

PMID- 14672106
TI  - What is the least costly strategy to evaluate cervical abnormalities in rural
      women? Comparing telemedicine, local practitioners, and expert physicians.
AB  - OBJECTIVE: This study establishes the least costly strategy for evaluation of
      rural women in need of colposcopy among 3 alternatives: telemedicine, local
      practitioners, and referral experts. METHODS: Women in rural Georgia who needed
      colposcopy were examined by an expert colposcopist on site, by a local
      practitioner, and by a distant expert colposcopist linked by telemedicine.
      Independent determinations of biopsy intent were used to model the differing
      biopsy costs of the 3 methods. Record review determined the average total cost of
      telemedicine. Reports of average cost in year 2000 dollars from societal
      perspective include medical costs and pain and suffering due to additional
      biopsies and curettage, telemedicine costs, and costs of potential diagnostic
      delay for a 1-year time horizon. RESULTS: From the societal perspective in the
      baseline case, the average cost per patient evaluated was dollar 270 for patients
      seen by referral experts. The cost was dollar 38 less (e.g., dollar 232) for
      patients seen by local practitioners, and dollar 35 more (e.g., dollar 305) for
      patients seen by telemedicine. From the societal perspective, local practitioners
      were less costly than referral experts because of lower travel costs for
      patients, but from the medical perspective, their average cost was dollar 32
      higher than referral experts because they performed more biopsies and curettage
      procedures than experts. Telemedicine assistance would have lowered the number of
      biopsies performed by local practitioners, but as of year 2000 the costs of this
      technology could not be justified by the savings. CONCLUSION: From the societal
      perspective, local practitioners performing colposcopy are the least costly way
      to evaluate cervical abnormalities in rural patients with substantial time and
      travel costs.

PMID- 14672108
TI  - Paper Standard Gamble: the reliability of a paper questionnaire to assess
      utility.
AB  - BACKGROUND: Quality of life is often best estimated by standard gamble
      techniques. However, these techniques usually require time-consuming and
      expensive interviews or computer-directed questionnaires. Paper Standard Gamble
      (PSG) is a paper questionnaire that has previously been shown to accurately
      represent standard gambles elicited by computer. The authors sought to
      demonstrate its test-retest reliability in comparison to other, paper-based
      measures of quality of life. METHODS: The authors used a longitudinal cohort
      design with duplicate assessments of quality of life by PSG, the Dermatology Life
      Quality Index, and the Mental and Physical Component Summary scores of the SF-12
      in stable dermatology out-patients. Baseline measures were performed by mail 1 to
      2 weeks before a scheduled dermatology clinic visit. Follow-up measures were
      performed in the waiting room before being seen by the dermatologist. The authors
      calculated the coefficient of variation and the Spearman rank correlation
      coefficient for each of the instruments. RESULTS: 74 patients with stable skin
      conditions participated. The coefficient of variation of PSG (0.47%) was smaller
      than the other instruments (4.26%-5.22%); PSG's correlation was higher (0.97 v.
      0.65-0.80). CONCLUSION: PSG, a 1-page paper questionnaire, is a reliable measure
      of patient utility suitable for use in postal surveys.

PMID- 14672109
TI  - A comparison of the health utilities indices Mark 2 and Mark 3 in type 2
      diabetes.
AB  - PURPOSE: Past research into health-related quality of life (HRQL) in diabetes
      using preference-based measures, such as the Health Utilities Index Mark 2 (HUI2)
      or the Health Utilities Index Mark 3 (HUI3), is sparse. Important differences
      between the HUI2 and HUI3 could lead to differences in their abilities to capture
      HRQL deficits in type 2 diabetes. This analysis compared the extent to which the
      HUI2 and HUI3 detect differences associated with varying levels of disease
      severity or advancement in type 2 diabetes. METHODS. This analysis was conducted
      as part of using baseline, cross-sectional data from a larger, prospective,
      controlled study of an intervention to improve care for individuals with type 2
      diabetes in rural communities in Alberta, Canada. The HU12 and HUI3 were self
      administered to 372 community-dwelling individuals with type 2 diabetes. RESULTS:
      Relative to HUI2 scores, larger differences in overall HUI3 scores were seen for
      comparisons for individuals presumed to have more advanced disease. The pain
      attribute of the HUI3 categorized a larger proportion of individuals as
      moderately to severely impaired (41.5% v. 24.2%, P < 0.001), as did the emotion
      attribute (20.5% v. 7.7%, P < 0.001). For individuals with negative overall HUI3
      scores, differences between overall HUI2 and HUI3 scores persisted after
      rescaling (mean difference = 0.33, P = 0.009). CONCLUSIONS: The greater range of
      possible scores on the HUI3, its relative ability to assess the utility of states
      worse than dead, and its relative superiority in discriminating moderate to
      severe impairment from mild or no impairment might favor its use over the HUI2 in
      type 2 diabetes.

PMID- 14672110
TI  - Attitudes, sociodemographic characteristics, and actual end-of-life decisions of
      physicians in Flanders, Belgium.
AB  - AIM: To study the effect of sociodemographic and attitudinal determinants of
      physicians making end-of-life decisions (ELDs). METHODS: The physicians having
      signed 489 consecutive death certificates in the city of Hasselt (Belgium) were
      sent an anonymous questionnaire regarding their ELDs and another on their
      attitudes toward voluntary euthanasia (EUTH) and physician-assisted suicide
      (PAS). RESULTS: 55% response rate. Nontreatment decisions occurred in 16.7% of
      all death cases; in 16%, there was potentially life-shortening use of drugs to
      alleviate pain and symptoms; in 4.8% of cases, death was deliberately induced by
      lethal drugs, including EUTH, PAS, and life termination without explicit request
      by the patient. In their attitudes toward EUTH and PAS, the 92 responding
      physicians clustered into 3 groups: positive and rule oriented, positive rule
      adverse, and opposed. Cluster group membership, commitment to life stance, years
      of professional experience, and gender were each associated with specific ELD
      making patterns.

PMID- 14672111
TI  - Variations in risk attitude across race, gender, and education.
AB  - BACKGROUND: Significant disparities in health care utilization exist across
      gender and race. Little is known about the patient-specific factors that may
      contribute to this variation. This study examined variations in risk attitude
      across major sociodemographic groups. METHODS: A survey elicited utility measures
      for health states under risk-insensitive and risk-sensitive conditions (time
      tradeoff and standard gamble methods, respectively). Risk attitude was modeled
      assuming constant proportional risk posture, thus the utility function used was a
      power function. A multivariable linear regression model was used to examine the
      relationship between risk attitude and sociodemographic factors. RESULTS: Of the
      62 study subjects, the mean age was 47.6 years, 47% were female, and 33% were
      African American. Overall, 37% of respondents were decidedly risk averse, 37%
      moderately risk averse, 15% moderately risk seeking, and 11% decidedly risk
      seeking. Significant predictors of increasing risk aversion in multivariate
      modeling were white race (P < 0.01) and lower education (P < 0.05). Women also
      tended to be more risk averse (P = 0.07). CONCLUSIONS: This study found
      significant differences in risk attitude across race and educational status, with
      a smaller difference across gender. Further research is needed to validate these
      findings and clarify their contribution to racial and gender variations in health
      care utilization and their future role in decision and cost-effectiveness
      analyses.

PMID- 14672112
TI  - When is it worth introducing a quality improvement program? A mathematical model.
AB  - Quality improvement programs must compete with other health care interventions
      for limited health care resources. The goal of the research presented here was to
      develop a model that portrays the mathematical relationship between the size of a
      quality deficit caused by the noncompliance of health professionals and the cost
      effectiveness of a quality improvement program. The model allows the
      determination of the minimum size of a quality deficit for which it is worth
      introducing a quality improvement program. If a quality improvement program has
      already been implemented, the model can be used to define the quality threshold
      beyond which a reduction in quality becomes economically unattractive. An example
      considering the reduction of underuse in depression treatment demonstrates that
      an intervention with a favorable cost-effectiveness ratio may become economically
      unattractive once the costs for the implementation effort are considered.

PMID- 14672113
TI  - The use of fixed- and random-effects models for classifying hospitals as
      mortality outliers: a Monte Carlo assessment.
AB  - BACKGROUND: There is an increasing movement towards the release of hospital
      "report-cards. "However, there is a paucity of research into the abilities of the
      different methods to correctly classify hospitals as performance outliers.
      OBJECTIVE: To examine the ability of risk-adjusted mortality rates computed using
      conventional logistic regression and random-effects logistic regression models to
      correctly identify hospitals that have higher than acceptable mortality. RESEARCH
      DESIGN: Monte Carlo simulations. MEASURES: Sensitivity, specificity, and positive
      predictive value of a classification as a high-outlier for identifying hospitals
      with higher than acceptable mortality rates. RESULTS: When the distribution of
      hospital specific log-odds of death was normal, random-effects models had greater
      specificity and positive predictive value than fixed-effects models. However,
      fixed-effects models had greater sensitivity than random-effects models.
      CONCLUSIONS: Researchers and policy makers need to carefully consider the balance
      between false positives and false negatives when choosing statistical models for
      determining which hospitals have higher than acceptable mortality in performance
      profiling.

PMID- 14672115
TI  - Adsorption and desorption of atrazine by three soils.

PMID- 14672114
TI  - Health-state valuations have been core issues in the field of medical decision
      making.

PMID- 14672116
TI  - Novel atoxic method of flavonoid extraction from Ginkgo biloba leaves.

PMID- 14672117
TI  - Inclusion effects of highly water-soluble cyclodextrins on the solubility,
      photodegradation, and acute toxicity of methyl parathion.

PMID- 14672118
TI  - Effect of addition of sodium hydroxide and calcium nitrate on polycyclic aromatic
      hydrocarbon emission from benzene incineration.

PMID- 14672119
TI  - In situ XANES study of electrokinetic remediation of cadmium-contaminated soils.

PMID- 14672120
TI  - 1,2,4-Trichlorobenzene induction of chromosomal aberrations and cell division of
      root-tip cells in Vicia faba seedlings.

PMID- 14672121
TI  - Effect of cadmium on root exudes of wheat (Triticum aestivm L.) under different
      cultures media.

PMID- 14672122
TI  - Changes in soil solution heavy metal concentrations over time following EDTA
      addition to a Chinese paddy soil.

PMID- 14672123
TI  - Evaluation of Cd uptake by plants estimated from total soil Cd, pH, and organic
      matter.

PMID- 14672124
TI  - Effect of thiophanate-methyl on the reproduction and survival of the freshwater
      rotifer Brachionus calyciflorus Pallas.

PMID- 14672125
TI  - Numerical modeling for remediation of contaminated land and groundwater.

PMID- 14672126
TI  - Solute and contaminant transport in heterogeneous soils.

PMID- 14672127
TI  - Binary-joint effects of acetochlor, methamidophos, and copper on soil microbial
      population.

PMID- 14672128
TI  - Effect of agrochemicals on nematode community structure in a soybean field.

PMID- 14672129
TI  - Nutrient loss from an agricultural catchment and landscape modeling in southeast
      China.

PMID- 14672130
TI  - Characterization of bacteria capable of degrading soil-sorbed biphenyl.

PMID- 14672131
TI  - Cadmium concentrations in a boreal forest ecosystem after application of wood
      ash.

PMID- 14672132
TI  - Ecotoxicological examination of sediment extracts of Huaihe River, China by in
      vitro bioassays.

PMID- 14672133
TI  - Removal of copper from water by activated carbon.

PMID- 14672134
TI  - X-ray absorption spectroscopic studies of As-humic substances in the ground water
      of the Taiwan blackfoot disease area.

PMID- 14672135
TI  - Speciation of copper in a contaminated soil.

PMID- 14672136
TI  - Microbial degradation of the endocrine-disrupting chemicals phthalic acid and
      dimethyl phthalate ester under aerobic conditions.

PMID- 14672137
TI  - Thermal treatment of heavy metal in incinerator fly ashes.

PMID- 14672138
TI  - Identification of Escherichia coli O157:H7 with oligonucleotide arrays.

PMID- 14672139
TI  - Characterization of lead species in Al2O3 contaminated with lead(II).

PMID- 14672140
TI  - Immobilization of chromium(VI) with debris of aquatic plants.

PMID- 14672141
TI  - Characterization of copper sorbed by a compost.

PMID- 14672142
TI  - Volatile organic compound emissions during cold-starts of motorcycles.

PMID- 14672143
TI  - Speciation of chromium in an electroplating sludge during thermal stabilization.

PMID- 14672144
TI  - Nitrogen discharge from aquacultural ponds and the possible impacts on aquatic
      environment.

PMID- 14672145
TI  - Presence and place of main ideas and examples in study texts.
AB  - BACKGROUND: How indispensable are examples and main ideas in study texts? In
      research into comprehension of expository texts examples are sometimes considered
      as cognitive support, sometimes as seductive details. According to the
      cognitivist view, text comprehension is based on main ideas, whereas the
      constructivist view holds that examples are the basis of understanding. AIMS:
      This study explored how text comprehension is influenced by main ideas and
      examples in study texts, in relation to Vermunt's (1992, 1998) 'concrete
      elaboration' learning style. In Experiment 1, concrete texts with many examples
      were compared with abstract texts with many main ideas. In Experiment 2, idea
      oriented texts, in which main ideas preceded examples, were compared with example
      oriented texts, in which examples preceded main ideas. SAMPLES: In both
      experiments, undergraduate social sciences students studied various versions of
      an introductory text on educational psychology. METHODS: The text contained
      sections with a varying number of relevant and irrelevant examples and with or
      without a main idea (Experiment 1), and sections with a main idea followed by
      examples, sections with a main idea without examples, or sections with examples
      followed by a main idea (Experiment 2). After studying the text, students
      completed a verbatim recognition test and an explanation test. RESULTS: Best
      results were obtained after studying sections with a main idea and two or five
      examples. Irrelevant examples were detrimental to understanding. Students used
      examples to construct knowledge or to activate prior knowledge. Students with a
      strong habit of concrete elaboration used main ideas to recollect episodes of
      personal experience. This may interfere with understanding underlying concepts
      and principles by relating main ideas to examples in the text. Students with a
      low score on the concrete elaboration scale were sensitive to the presence of
      examples in the study text. CONCLUSION: In expository texts, examples are
      indispensable. The findings suggest that main ideas are useful, and, in order to
      prevent interference effects, the more so when they are put at the end of
      sections.

PMID- 14672146
TI  - The influence of shyness on children's test performance.
AB  - BACKGROUND: Research has shown that shy children differ from their peers not only
      in their use of language in routine social encounters but also in formal
      assessments of their language development, including psychometric tests of
      vocabulary. There has been little examination of factors contributing to these
      individual differences. AIMS: To investigate cognitive-competence and social
      anxiety interpretations of differences in children's performance on tests of
      vocabulary. To examine the performance of shy and less shy children under
      different conditions of test administration, individually with an examiner or
      among their peers within the familiar classroom setting. SAMPLE: The sample
      consisted of 240 Year 5 pupils (122 male, 118 female) from 24 primary schools.
      METHOD: Shy and less shy children, identified by teacher nomination and checklist
      ratings, completed vocabulary and mental arithmetic tests in one of three
      conditions, in a between-subjects design. The conditions varied individual and
      group administration, and oral and written responses. RESULTS: The conditions of
      test administration influenced the vocabulary test performance of shy children.
      They performed significantly more poorly than their peers in the two face-to-face
      conditions but not in the group test condition. A comparable trend for the
      arithmetic test was not statistically significant. Across the sample as a whole,
      shyness correlated significantly with test scores. CONCLUSIONS: Shyness does
      influence children's cognitive test performance and its impact is larger when
      children are tested face-to-face rather than in a more anonymous group setting.
      The results are of significance for theories of shyness and have implications for
      the assessment of schoolchildren.

PMID- 14672147
TI  - When teachers go the extra mile: foci of organisational identification as
      determinants of different forms of organisational citizenship behaviour among
      schoolteachers.
AB  - BACKGROUND: Psychological variables should play an important role in determining
      teachers' involvement in behaviours not directly or formally forced by contracts.
      Organisational identification as proposed from the Social Identity Approach is
      examined as a possible determinant of organisational citizenship behaviour (OCB)
      among schoolteachers. AIM: The aim of the present study was to explore the
      relationships between different foci of organisational identification and
      different forms of OCB in schools. SAMPLE: Data sets of altogether 447 German
      school teachers who filled in all relevant items in a cross-sectional
      questionnaire are used for analyses in the present study. METHODS: Standardised
      questionnaires measuring organisational identification and OCB were administered.
      RESULTS: Exploratory and confirmatory factor analyses revealed the proposed foci
      of identification (i.e., career identification, team identification, and
      organisational identification), as well as different forms of OCB (i.e., OCB
      towards the own qualification, towards the team, and towards the organisation).
      Structural equation modelling supports the main hypothesis that foci of
      identification relate differentially to forms of OCB. CONCLUSIONS: The results
      emphasise the importance of organisational identification as a determinant of OCB
      in schools. Practical implications are discussed.

PMID- 14672148
TI  - Secondary school teachers' attitudes towards and beliefs about ability grouping.
AB  - BACKGROUND: Internationally and historically considerable research has been
      undertaken regarding the attitudes of secondary school teachers towards different
      types of ability grouping. There has been no recent research taking account of
      the changing educational context in the UK. AIMS: This paper aims to explore
      secondary school teachers' attitudes and beliefs about ability grouping taking
      account of school type, gender, experience and qualifications. SAMPLE: The sample
      comprised over 1,500 teachers from 45 schools divided into three groups based on
      their ability grouping practices in years 7-9 (the students were aged 11-14). The
      sample included all the lower school teachers of mathematics, science and English
      and a random sample of teachers from other subjects in each school. METHODS:
      Teachers responded to a questionnaire which explored their attitudes towards
      ability grouping through the use of rating scales and open-ended questions.
      RESULTS: The findings showed that the teachers' beliefs broadly reflected
      research findings on the actual effects of ability grouping, although there were
      significant differences relating to the type of school they taught in and the
      subject that they taught. Separate analysis of school types showed that length of
      time teaching, individual school differences and teacher qualifications were also
      significant predictors of attitudes. CONCLUSIONS: Teachers' beliefs about ability
      grouping are influenced by the type of groupings adopted in the school where they
      work, the subject that they teach, their experience and qualifications. As
      pedagogical practices are known to be influenced by beliefs these findings have
      important implications for teacher training.

PMID- 14672149
TI  - Learning styles: self-reports versus thinking-aloud measures.
AB  - BACKGROUND: Learning styles are often assessed through students' self-reports on
      instruments such as Vermunt's Inventory of Learning Styles (ILS). Recent
      research, however, has questioned the adequacy of questionnaires for the
      assessment of learning styles. AIMS: The objective of this paper is to evaluate
      methods of learning style assessment as a means for identifying students at risk.
      Therefore, the ILS as a self-report instrument will be compared with the
      students' actual study processes, assessed through the thinking-aloud method.
      SAMPLE: In the first study 1,060 students from the Technical University of Delft
      participated. Thirty-three of them were selected on the ILS for participation in
      the second study. METHOD: The ILS was administered to the 1,060 participants and
      their study results (GPA and credit points) were collected. Next, the selected 33
      participants studied a technical text while thinking aloud. Knowledge acquisition
      was measured by means of a post-test. Thinking-aloud protocols were analysed on
      frequencies of study activities, thus representing process measures of learning
      styles. RESULTS: The ILS proved to be a rather weak predictor of study results in
      Study 1. Results from Study 2 show hardly any correspondence between ILS and
      study process measures, although principal component structures of both measures
      were highly similar. Furthermore, study process measures outweighed the ILS in
      the prediction of study results (post-test, GPA and credit points). CONCLUSIONS:
      Learning style theory was confirmed by results on the study process measures. The
      assessment of learning styles through self-report instruments such as the ILS,
      however, should be reconsidered.

PMID- 14672150
TI  - Experimental analysis of students' course selection.
AB  - BACKGROUND: Prior to every term, students must select courses (i.e., academic
      units of instruction within a degree programme) to determine their study
      programme. Course selection (CS) is a sequential decision-making (DM) process-
      students weigh various types of information available about each course. Every
      decision influences the weighting of considerations for the next. This study is
      focused on three central dimensions of CS: Learning Value (low or high in being
      intellectually challenging, interesting and thought-provoking), Lecturer's Style
      (low or high--exciting, charismatic and humorous versus dry, inflexible, unclear,
      etc.), and Course Difficulty (easy, moderate or hard). AIMS: (1) To examine
      students' preferences for each dimension in five choices and in their sequential
      location (1st to 5th). (2) To trace compromises in dilemma situations after the
      desirable combinations had already been selected. (3) To investigate differential
      selection as a function of students' age, gender, and academic standing (average
      grades). SAMPLE: Advanced undergraduates in various departments in an Israeli
      university (N = 1,007). METHOD: In an experimental design, respondents were
      presented with 12 course descriptions representing 2x2x3 combinations, and asked
      to select five courses in a sequential order. RESULTS: The 12 courses were found
      to be empirically divided into: ideal courses (2), first-degree (4) and second
      degree (4) compromises, and rejected courses (2). Students avoided selecting hard
      courses unless they had no choice. Learning Value was the most preferred
      dimension, followed closely by Lecturer Style. Correlations showed that older and
      higher achieving students chose more difficult and high Learning Value courses.
      COMMENTS: The discussion centred on the methodological issue of the effectiveness
      of an experimental design for the investigation of CS, conceptual issues
      concerning Course Difficulty in students' selection and evaluation, and applied
      issues concerning the availability of information about the three investigated
      dimensions to students in real-life CS.

PMID- 14672151
TI  - A nonparametric item analysis of a selected item subset of the learning process
      questionnaire.
AB  - BACKGROUND: Although there have been numerous studies conducted on the
      psychometric properties of Biggs' Learning Process Questionnaire (LPQ), these
      have involved the use of traditional omnibus measures of scale quality such as
      corrected item total correlations, internal consistency estimates of reliability,
      and factor analysis. However, these omnibus measures of scale quality are sample
      dependent and fail to model item responses as a function of trait level. And
      since the item trait relationship is typically nonlinear, traditional factor
      analytic methods are inappropriate. AIMS: The purpose of this study was to
      identify a unidimensional subset of LPQ items and examine the effectiveness of
      these items and their options in discriminating between changes in the underlying
      trait level. In addition to assessing item quality, we were interested in
      assessing overall scale quality with non-sample dependent measures. METHOD: The
      sample was split into two nearly equal halves, and a undimensional subset of
      items was identified in one of these samples and cross-validated in the other.
      The nonlinear relationship between the probability of endorsing an item option
      and the underlying trait level was modelled using a nonparametric latent trait
      technique known as kernel smoothing and implemented with the program TestGraf.
      After item and scale quality were established, maximum likelihood estimates of
      participants' trait level were obtained and used to examine grade and gender
      differences. RESULTS: A undimensional subset of 16 deep and achieving items was
      identified. Slightly more than half of these items needed some of their options
      combined so that the probability of endorsing an item option as a function of
      increasing trait level corresponded to the ideal rank ordering of the item
      options. With this adjustment, scale quality as measured by the information
      function and standard error function was found to be good. However, no
      statistically significant gender differences were observed and, although
      statistically significant grade differences were observed, they were not
      substantively meaningful. CONCLUSIONS: The use of nonparametric kernel-smoothing
      techniques is advocated over parametric latent trait methods for the analysis of
      attitudinal and psychological measures involving polychotomous ordered-response
      categories. It is also suggested that latent trait methods are more appropriate
      than traditional test-based measures for studying differential item functioning
      both within and between cultures. Nonparametric kernel-smoothing techniques hold
      particular promise in identifying and understanding cross-cultural differences in
      student approaches to learning at both the item and scale level.

PMID- 14672152
TI  - Psychometric properties of the movement assessment battery for children-checklist
      as a screening instrument for children with a developmental co-ordination
      disorder.
AB  - BACKGROUND: The Checklist of the Movement Assessment Battery for Children (M-ABC)
      was developed to screen children for movement difficulties in the school
      situation. However, the psychometric properties of the Checklist have not been
      investigated in detail. AIM: The psychometric properties of the M-ABC Checklist
      were investigated including its usefulness as a screening instrument. SAMPLES: A
      group of 120 children, 6 to 11 years old, randomly selected from mainstream
      schools and a group of 64 children, 6 to 9 years old, referred for assessment of
      their motor functioning. METHODS: A reliability analysis was performed to
      investigate whether the 48 items of the Checklist measure the same construct.
      Construct validity was investigated by means of a factor analysis. And lastly,
      the sensitivity, specificity and positive predictive value of the Checklist were
      investigated by comparing the performance of children on both the Test and
      Checklist of the M-ABC. RESULTS: The items of the Checklist measure the same
      construct. Seven factors were obtained after factor analysis, revealing that the
      Checklist measures a broad range of motor skills. The Checklist met the standards
      for sensitivity in all age groups, except in the 8-year-old group, where too many
      children with motor problems were not detected. With the exception of the 6-year
      old children, specificity was poor. The positive predictive value was acceptable,
      except for the 7-year-old children. CONCLUSION: The Checklist proved to meet
      standards for reliability and most aspects of validity. Its use by teachers for
      screening children with movement difficulties can be recommended.

PMID- 14672153
TI  - Strategy-dependent changes in memory: effects on behavior and brain activity.
AB  - In the present study, an implicit strategy manipulation was used to explore the
      contribution of memory strategy to brain activation and behavioral performance.
      Participants were biased to use either a short-term (maintenance-focused) or long
      term (retrieval-focused) memory strategy within a single memory task through
      manipulation of task context. In comparing directly matched trials across the
      different task contexts, we observed clear changes in both behavioral performance
      and brain activity across a network of regions located primarily within lateral
      and medial frontal cortex. These effects of the memory strategy manipulation
      suggest that when a retrieval-focused strategy is induced, mnemonic processes are
      preferentially engaged during the encoding period. In contrast, when a
      maintenance-focused strategy is induced, mnemonic processes are preferentially
      engaged during the delay and response periods. Taken together, the results imply
      that covert cognitive strategies play an important role in modulating brain
      activation and behavior during memory tasks.

PMID- 14672154
TI  - Evaluating the neuropsychological dissociation evidence for multiple memory
      systems.
AB  - This article presents a critical evaluation of the logic and nature of the
      neuropsychological dissociation evidence that has provided one of the essential
      lines of support for claims of multiple memory systems--specifically, suggesting
      that amnesia selectively compromises, and an intact hippocampal system
      selectively supports, a particular form of memory. An analysis of the existing
      neuropsychological dissociation evidence is offered in which different classes of
      evidence--different dissociation approaches-are identified and characterized. The
      logic of these neuropsychological dissociation approaches is evaluated critically
      in terms of their ability to distinguish among alternative theoretical views. We
      conclude that although they support a multiple memory systems account, the
      findings from these types of neuropsychological dissociation, taken individually
      and without support from other converging lines of cognitive neuroscience
      evidence, cannot definitively rule out alternative formulations. A more powerful
      neuropsychological dissociation approach is then outlined, involving dissociation
      within condition, that, by more effectively limiting the critical domains of
      difference between the dissociated performances, can successfully rule out
      alternative accounts. Its application in Ryan, Althoff, Whitlow, and Cohen (2000)
      is described, providing strong support for the power of the dissociation within
      condition approach.

PMID- 14672155
TI  - Disproportionate deficit in associative recognition relative to item recognition
      in global amnesia.
AB  - In two experiments, we tested the hypothesis that medial temporal lobe (MTL)
      amnesic patients and, likewise, diencephalic (DNC) amnesic patients evidence a
      disproportionate deficit in memory for associations in comparison with memory for
      single items. In Experiment 1, we equated item recognition in amnesic and control
      participants and found that, under these conditions, associative recognition
      remained impaired both for MTL patients and for DNC patients. To rule out an
      alternative interpretation of the results of Experiment 1, in Experiment 2 we
      compared the performance of amnesic and control participants on a one-item
      recognition task and a two-item recognition task that required no memory for the
      association between members of word pairs. In the MTL group, when single-item
      recognition was equated to that of the controls, two-item nonassociative pair
      memory was equivalent as well. In the DNC group, nonassociative pair memory was
      impaired, but this impairment did not fully account for the impairment in
      associative memory. These findings indicate that memory for novel associations
      between items is disproportionately impaired in comparison with memory for single
      items in amnesia.

PMID- 14672156
TI  - Early modulation of visual perception by emotional arousal: evidence from steady
      state visual evoked brain potentials.
AB  - Allocation of processing resources to emotional picture stimuli was examined
      using steady-state visual evoked brain potentials (ssVEPs). Participants viewed a
      set of 60 colored affective pictures from the International Affective Picture
      System, presented in a flickering mode at 10 Hz in order to elicit ssVEPs. Phase
      and amplitude of the 10-Hz ssVEP were examined for six picture categories: threat
      and mutilation (unpleasant), families and erotica (pleasant), and household
      objects and persons (neutral). Self-reported affective arousal and hedonic
      valence of the picture stimuli were assessed by means of subjective ratings.
      Viewing affectively arousing (unpleasant and pleasant) pictures was associated
      with enhanced ssVEP amplitude at parieto-occipital recording sites, as compared
      with neutral stimuli. Phase information suggested increased coactivation of right
      occipitotemporal and frontotemporal sources during processing of affectively
      arousing stimuli. These findings are consistent with reentrant modulation of
      early visual processing by distributed networks including subcortical and
      neocortical structures according to a stimulus's motivational relevance.

PMID- 14672158
TI  - The neural basis of autobiographical and semantic memory: new evidence from three
      PET studies.
AB  - A novel, neuropsychologically informed paradigm (extended retrieval of events in
      response to a cue word) was used to investigate the neural basis of
      autobiographical and semantic memory. Contrasting retrieval of autobiographical
      memories with retrieval of semantic facts (ABM-SEM) in 24 subjects across three
      PET studies revealed bilateral involvement of the middle temporal gyrus (BA 21)
      and medial frontal cortex (BA 9/10). The opposite contrast, SEM-ABM, resulted in
      increased regional cerebral blood flow in left posterior temporal regions (BA 37)
      and left prefrontal cortex (BA 45/46). Laterality maps suggest that the bilateral
      pattern seen in our studies, but not often in other neuroimaging investigations,
      reflects the use of a task stressing retrieval of specific personal events.
      Further comparisons revealed that the activation in the right anterior temporal
      lobe during autobiographical recall was virtually identical to that seen during
      retrieval of information about famous people or events in contrast with retrieval
      of general semantic facts. These findings suggest that the retrieval of an
      autobiographical event requires participation from conceptual knowledge, and that
      this type of knowledge is bilaterally distributed in the temporal lobes.

PMID- 14672159
TI  - Color constancy and the functional significance of McCollough effects.
AB  - A central problem in visual perception concerns how humans perceive stable and
      uniform object colors despite variable lighting conditions (i.e. color
      constancy). One solution is to 'discount' variations in lighting across object
      surfaces by encoding color contrasts, and utilize this information to 'fill in'
      properties of the entire object surface. Implicit in this solution is the caveat
      that the color contrasts defining object boundaries must be distinguished from
      the spurious color fringes that occur naturally along luminance-defined edges in
      the retinal image (i.e. optical chromatic aberration). In the present paper, we
      propose that the neural machinery underlying color constancy is complemented by
      an 'error-correction' procedure which compensates for chromatic aberration, and
      suggest that error-correction may be linked functionally to the experimentally
      induced illusory colored aftereffects known as McCollough effects (MEs). To test
      these proposals, we develop a neural network model which incorporates many of the
      receptive-field (RF) profiles of neurons in primate color vision. The model is
      composed of two parallel processing streams which encode complementary sets of
      stimulus features: one stream encodes color contrasts to facilitate filling-in
      and color constancy; the other stream selectively encodes (spurious) color
      fringes at luminance boundaries, and learns to inhibit the filling-in of these
      colors within the first stream. Computer simulations of the model illustrate how
      complementary color-spatial interactions between error-correction and filling-in
      operations (a) facilitate color constancy, (b) reveal functional links between
      color constancy and the ME, and (c) reconcile previously reported anomalies in
      the local (edge) and global (spreading) properties of the ME. We discuss the
      broader implications of these findings by considering the complementary
      functional roles performed by RFs mediating color-spatial interactions in the
      primate visual system.

PMID- 14672160
TI  - Neural network models for the gaze shift system in the superior colliculus and
      cerebellum.
AB  - We investigate the role that the superior colliculus (SC) and the cerebellum
      might play in generating gaze shifts. The discharge of cells in the intermediate
      layers of the SC is tightly linked to the occurrence of saccades. Many studies
      have demonstrated that the cerebellum is involved in both eye and head movements.
      When the head is unrestrained, large amplitude gaze shifts are composed of
      coordinated eye and head movements. In this study, we propose that the gaze
      saccades system is controlled by a feedback loop between the SC and the
      cerebellum. The SC only encodes retinal coordinates and controls the eye
      displacement (to move the fovea to the target), while the cerebellum deals with
      the gaze programming and controls the head displacement. When a target appears in
      space, the buildup cells within the SC decode the target signal in the retina
      before the saccade onset, and input the signal of the gaze displacement to the
      cerebellum. The cells in the cerebellum vermis encode the initial position of the
      eye in the orbit. The gaze displacement is decomposed into the head amplitude and
      the eye amplitude within the cerebellum. There are two output signals from the
      cerebellum. One signal controls the head movement. The other is projected back to
      the SC, and forms a component of the saccade vector to control the eye movement.
      The sum of the vectors provided by the cerebellum and the vector provided by the
      burst cells in the SC indicates the direction and the amplitude of the desired
      movement of the eye during the saccade. We propose a cerebellum model to predict
      the displacements of the eye and head under the condition that the position of
      the target signal in the retina and the initial position of the eye in the orbit
      are known. The results from the model are close to that observed physiologically.
      We conclude that before gaze shift onset, the cerebellum may play an important
      role in decomposing the gaze displacement into an eye amplitude and head
      amplitude signal.

PMID- 14672157
TI  - Functional neuroanatomy of emotions: a meta-analysis.
AB  - The application of functional neuroimaging to the study of human emotion has
      yielded valuable data; however, the conclusions that may be drawn from any one
      study are limited. We applied novel statistical techniques to the meta-analysis
      of 106 PET and fMRI studies of human emotion and tested predictions made by key
      neuroscientific models. The results demonstrated partial support for asymmetry
      accounts. Greater left-sided activity was observed for approach emotions, whereas
      neural activity associated with negative/withdrawal emotions was symmetrical.
      Support was also found for affect program emotion accounts. The activation
      distributions associated with fear, disgust, and anger differed significantly.
      These emotions were most consistently associated in activity in regions
      associated with selective processing deficits when damaged: the amygdala, the
      insula and globus pallidus, and the lateral orbitofrontal cortex, respectively.
      In contrast, the distributions for happiness and sadness did not differ. These
      findings are considered in the context of conceptualizations of the neural
      correlates of human emotion.

PMID- 14672161
TI  - A complex-valued version of Nagumo-Sato model of a single neuron and its
      behavior.
AB  - The Nagumo-Sato model of a single neuron was extended so that it can handle
      complex numbers and the behavior of the complex-valued model was investigated.
      The model neuron receives its past outputs through a complex-valued weight and
      fires when the absolute value of the membrane potential exceeds a threshold. Some
      of the basic features of the model, such as associated with fixed points and
      period-two orbits, were derived. The main purpose of the paper is to show the
      model's chaotic behavior which is the result of the extension to the complex
      numbers and different from that of the original real-valued model. The apparently
      chaotic orbits were numerically shown to have positive Lyapunov exponents and
      high sensitivity to the initial conditions. Some of the chaotic orbits seem to be
      related to the saddles of period-two and their associated stable and unstable
      manifolds.

PMID- 14672162
TI  - Delay-dependent exponential stability analysis of delayed neural networks: an LMI
      approach.
AB  - For neural networks with constant or time-varying delays, the problems of
      determining the exponential stability and estimating the exponential convergence
      rate are studied in this paper. An approach combining the Lyapunov-Krasovskii
      functionals with the linear matrix inequality is taken to investigate the
      problems, which provide bounds on the interconnection matrix and the activation
      functions, so as to guarantee the systems' exponential stability. Some criteria
      for the exponentially stability, which give information on the delay-dependence
      property, are derived. The results obtained in this paper provide one more set of
      easily verified guidelines for determining the exponentially stability of delayed
      neural networks, which are less conservative and less restrictive than the ones
      reported so far in the literature.

PMID- 14672163
TI  - Global stability of neural networks with distributed delays.
AB  - Using the Lyapunov functional approach, we study the global stability of a class
      of neural networks with distributed delays. Without assuming the boundedness,
      monotonicity and differentiability of the activation functions and symmetry of
      the interconnection matrix, we give some new sufficient conditions on the
      existence, uniqueness and global asymptotic stability of the equilibrium point.
      Our results improve, extend and complement some existing ones.

PMID- 14672164
TI  - SpikeCell: a deterministic spiking neuron.
AB  - We present a model of spiking neuron that emulates the output of the usual static
      neurons with sigmoidal activation functions. It allows for hardware
      implementations of standard feedforward networks, trained off-line with any
      classical learning algorithm (i.e. back-propagation and its variants). The model
      is validated on hand-written digits recognition, and image classification tasks.
      A digital architecture is proposed and evaluated. The area needed for
      implementing the spiking neuron on a chip is 10 times smaller than that for the
      corresponding static neuron. The accuracy of the network's output increases with
      time, and reaches that of the emulated static neural network after an adequate
      integration period. Single errors in the spike trains, or interruption of the
      relaxation process, due for example to irradiation in harsh environments, are
      harmless.

PMID- 14672165
TI  - A feed-forward network for input that is both categorical and quantitative.
AB  - The data on which a multi-layer perceptron (MLP) is to be trained to approximate
      a continuous function may have inputs that are categorical rather than numeric or
      quantitative such as color, gender, race, etc. A categorical variable causes a
      discontinuous relationship between an input variable and the output. A MLP, with
      connection matrices that multiply input values and sigmoid functions that further
      transform values, represents a continuous mapping in all input variables. A MLP
      therefore requires that all inputs correspond to numeric, continuously valued
      variables and represents a continuous function in all input variables. The way
      that this problem is usually dealt with is to replace the categorical values by
      numeric ones and treat them as if they were continuously valued. However, there
      is no meaningful correspondence between the continuous quantities generated this
      way and the original categorical values. Another approach is to encode the
      categorical portion of the input using 1-out-of-n encoding and include this code
      as input to the MLP. The approach in this paper is to segregate categorical
      variables from the continuous independent variables completely. The MLP is
      trained with multiple outputs; a separate output unit for each of the allowed
      combination of values of the categorical independent variables. During training
      the categorical value or combination of categorical values determines which of
      the output units should have the target value on it, with the remaining outputs
      being 'do not care'. Three data sets were used for comparison of methods. Results
      show that this approach is much more effective than the conventional approach of
      assigning continuous variables to the categorical features. In case of the data
      set where there were several categorical variables the method proposed here is
      also more effective than the 1-out-of-n input method.

PMID- 14672167
TI  - An intelligent sales forecasting system through integration of artificial neural
      networks and fuzzy neural networks with fuzzy weight elimination.
AB  - Sales forecasting plays a very prominent role in business strategy. Numerous
      investigations addressing this problem have generally employed statistical
      methods, such as regression or autoregressive and moving average (ARMA). However,
      sales forecasting is very complicated owing to influence by internal and external
      environments. Recently, artificial neural networks (ANNs) have also been applied
      in sales forecasting since their promising performances in the areas of control
      and pattern recognition. However, further improvement is still necessary since
      unique circumstances, e.g. promotion, cause a sudden change in the sales pattern.
      Thus, this study utilizes a proposed fuzzy neural network (FNN), which is able to
      eliminate the unimportant weights, for the sake of learning fuzzy IF-THEN rules
      obtained from the marketing experts with respect to promotion. The result from
      FNN is further integrated with the time series data through an ANN. Both the
      simulated and real-world problem results show that FNN with weight elimination
      can have lower training error compared with the regular FNN. Besides, real-world
      problem results also indicate that the proposed estimation system outperforms the
      conventional statistical method and single ANN in accuracy.

PMID- 14672166
TI  - A spiking neuron model: applications and learning.
AB  - This paper presents a biologically inspired, hardware-realisable spiking neuron
      model, which we call the Temporal Noisy-Leaky Integrator (TNLI). The dynamic
      applications of the model as well as its applications in Computational
      Neuroscience are demonstrated and a learning algorithm based on postsynaptic
      delays is proposed. The TNLI incorporates temporal dynamics at the neuron level
      by modelling both the temporal summation of dendritic postsynaptic currents which
      have controlled delay and duration and the decay of the somatic potential due to
      its membrane leak. Moreover, the TNLI models the stochastic neurotransmitter
      release by real neuron synapses (with probabilistic RAMs at each input) and the
      firing times including the refractory period and action potential repolarisation.
      The temporal features of the TNLI make it suitable for use in dynamic time
      dependent tasks like its application as a motion and velocity detector system
      presented in this paper. This is done by modelling the experimental velocity
      selectivity curve of the motion sensitive H1 neuron of the visual system of the
      fly. This application of the TNLI indicates its potential applications in
      artificial vision systems for robots. It is also demonstrated that Hebbian-based
      learning can be applied in the TNLI for postsynaptic delay training based on
      coincidence detection, in such a way that an arbitrary temporal pattern can be
      detected and recognised. The paper also demonstrates that the TNLI can be used to
      control the firing variability through inhibition; with 80% inhibition to
      concurrent excitation, firing at high rates is nearly consistent with a Poisson
      type firing variability observed in cortical neurons. It is also shown with the
      TNLI, that the gain of the neuron (slope of its transfer function) can be
      controlled by the balance between inhibition and excitation, the gain being a
      decreasing function of the proportion of inhibitory inputs. Finally, in the case
      of perfect balance between inhibition and excitation, i.e. where the average
      input current is zero, the neuron can still fire as a result of membrane
      potential fluctuations. The firing rate is then determined by the average input
      firing rate. Overall this work illustrates how a hardware-realisable neuron model
      can capitalise on the unique computational capabilities of biological neurons.

PMID- 14672168
TI  - Physical properties of cream reformulated with fractionated milk fat and milk
      derived components.
AB  - Emulsifying properties of milk-derived components influence the physical
      characteristics of reformulated creams. Fractionated butter oils with different
      melting ranges (low-melt: 10 to 25 degrees C; medium-melt: 25 to 35 degrees C)
      were recombined into fluid dairy systems using skim milk, or sweet buttermilk and
      butter-derived aqueous phase to manufacture 20% milk fat creams. Separation
      temperature (49 degrees C or 55 degrees C) in obtaining emulsifying components
      was examined for its effect on physical properties of pasteurized reformulated
      creams. Rate of creaming, viscosity, feathering, and sensory characteristics of
      reformulated and natural creams stored at 3.3 degrees C were evaluated over a 13
      d period. Creaming rate of reformulated and natural creams was unaffected by
      formulation and was most influenced by duration of storage. Melting
      characteristics of butter oils influenced viscosity at some shear rates. With the
      exception of natural cream, all formulations were consistent in apparent
      viscosity during the 2-wk storage period. All creams feathered in a pH range of
      4.70 to 5.20 and were classified as moderately stable to slightly unstable. All
      reformulated and natural creams met sensory quality specifications with the
      exception of creams formulated with skim milk and lower melting range butteroil.
      Creams formulated with buttermilk, butter-derived aqueous phase, and lower
      melting range butter oil most closely mimicked natural creams with regard to
      sensory quality and viscosity.

PMID- 14672169
TI  - Effects of pH, temperature, supplementation with whey protein concentrate, and
      adjunct cultures on the production of exopolysaccharides by Streptococcus
      thermophilus 1275.
AB  - Effects of pH, temperature, supplementation with whey protein concentrate (WPC),
      and non-EPS culture on the exopolysaccharide (EPS) production by Streptococcus
      thermophilus 1275 were studied. The organism was grown in 10% reconstituted skim
      milk (RSM) in a Biostat B fermenter for 24 h at various pH (4.5, 5.5 and 6.5) and
      temperatures (30, 37, 40, and 42 degrees C), and supplementation with WPC 392,
      and non-EPS producing S. thermophilus 1303 and the amount of EPS produced were
      determined. Bacterial counts were enumerated and the concentrations of lactic
      acid, lactose, glucose, and galactose were also determined. A maximum of 406 mg/L
      of EPS was produced in RSM at 37 degrees C after 24 h of fermentation at pH 4.08
      when the pH was not controlled. A pH of 5.5 and temperature of 40 degrees C were
      found to be optimal for EPS production by S. thermophilus 1275, yielding 458
      mg/L. The EPS production increased when RSM was supplemented with WPC 392. At
      optimum pH and at 37 degrees C with WPC supplementation, the level of EPS
      increased to 1029 mg/L. Co-culturing S. thermophilus 1275 with non-EPS S.
      thermophilus 1303 increased EPS production at 37 degrees C and pH 5.5 to 832
      mg/L. High temperature (42 degrees C) reduced the amount of EPS production, and
      EPS production ceased at pH 4.5 when maintained constantly at this pH. The level
      of lactose utilization and lactic acid production depended on growth conditions
      of the organism. No glucose was detected, while galactose was found to accumulate
      in the medium.

PMID- 14672170
TI  - Assimilation of cholesterol by yeast strains isolated from infant feces and Feta
      cheese.
AB  - Eight yeast strains isolated from infant feces and the traditional Greek Feta
      cheese, selected for their probiotic properties, were tested along with a
      commercially available strain of Saccharomyces boulardii for their ability to
      remove cholesterol from a growth medium (yeast extract glucose peptone broth)
      supplemented with 0.3% Oxgall. The amount of cholesterol removed during 72 h of
      growth at 37 degrees C revealed significant variations among the yeast strains
      examined. Two isolates from infant feces, namely Saccharomyces cerevisiae KK1 and
      Isaatchenkia orientalis KK5.Y.1 and one isolate from Feta cheese, namely S.
      cerevisiae 832, along with the commercial strain S. boulardii, were able to
      remove cholesterol from the growth medium after 48 h of incubation at 37 degrees
      C. However, Saccharomyces strains proved to be able to remove cholesterol even
      after 24 h of growth at 37 degrees C. The cholesterol removed from the growth
      medium was not metabolically degraded but was rather assimilated into the yeast
      cells. The ability to assimilate cholesterol in vitro and to tolerate low pH
      levels, gastric juice, and bile indicate that S. cerevisiae 832, and especially
      S. cerevisiae KK1 and I. orientalis KK5.Y.1 (being more bile and gastric juice
      tolerant because of their human origin) may be promising candidate strains for
      use as probiotics.

PMID- 14672171
TI  - The housekeeping genes GAPDH and cyclophilin are regulated by metabolic state in
      the liver of dairy cows.
AB  - Steady-state levels of mRNA are often used to infer treatment effects on the
      levels of the corresponding protein. In addition, an internal standard RNA is
      usually measured to document specificity of treatment and to correct for
      intersample variation. Our objective was to evaluate whether glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) and cyclophilin could be used as internal
      standards when studying changes in hepatic gene expression in dairy cows. Hepatic
      expression of GAPDH and cyclophilin was measured in 6 cows in late pregnancy (28
      d prepartum) and early lactation (10 d postpartum). Each gene displayed 2- to 3
      fold higher expression in early lactation than in late pregnancy. Next, we
      determined whether negative energy balance alone or in combination with exogenous
      growth hormone could mimic the effects of early lactation. Late-lactating cows
      were fed 120% of predicted energy requirements or 33% of maintenance
      requirements. During each feeding period, cows were administered excipient or
      bovine somatotropin in a single-reversal design with 4-d periods separated by a 2
      d interval. Underfeeding increased hepatic expression of GAPDH and cyclophilin by
      1- to 2-fold, whereas bovine somatotropin had no effect. Finally, the effects of
      insulin were studied by performing hyperinsulinemic-euglycemic clamps in late
      pregnancy (28 d prepartum) and early lactation (28 d postpartum).
      Hyperinsulinemia reduced GAPDH expression in both states, and cyclophilin
      expression in early lactation. In conclusion, GAPDH and cyclophilin are regulated
      in the liver of dairy cows and should not be used to standardize hepatic gene
      expression in studies involving the transition period, undernutrition, and
      sustained changes in plasma insulin.

PMID- 14672172
TI  - Imbalance between lipoxin A4 and leukotriene B4 in chronic mastitis-affected
      cows.
AB  - Persistent accumulation of inflammatory cells in the udder, with neutrophils
      being the predominant cell type, is a characteristic feature of chronic mastitis
      in dairy cows. Leukotriene (LT) B4 is a potent chemotactic agent, known to induce
      recruitment and accumulation of neutrophils in the bovine mammary gland. The LTB4
      stimulated neutrophil functional responses are closely opposed by lipoxin (LX)
      A4, which promotes the resolution of inflammation. We thus hypothesized that the
      chronic inflammation of the udder could be associated with an unfavorable ratio
      between these two eicosanoids and that the persistence of neutrophil accumulation
      could be due to an increase in LTB4 synthesis and/or an impaired LXA4 production.
      In an attempt to verify this hypothesis, we first measured LXA4, LTB4, and their
      ratio in the milk of healthy and acute and chronic mastitis-affected quarters.
      Next, we studied the relationships between these variables and the degree of
      udder inflammation as assessed by somatic cell count measurement. The LTB4
      concentration was low in healthy quarters, drastically increased in acute
      mastitis, and reached intermediate levels in chronic mastitis-affected quarters.
      However, whereas LXA4 concentration was highly increased in acute mastitis,
      healthy and chronic quarters had similarly low values. The LXA4:LTB4 ratio was
      thus significantly lower in chronic mastitis-affected cows. The LTB4
      concentrations measured in chronic quarters were highly correlated to somatic
      cell count and to milk neutrophil and macrophage numbers. A weaker correlation
      was observed between LXA4 and these variables. For both eicosanoids, the highest
      correlation was observed with the number of neutrophils. These results show the
      existence of an LXA4:LTB4 imbalance in chronic mastitis-affected cows because of
      low LXA4 concentrations. Further studies are needed to determine whether
      administration of LX or stable analogs could have therapeutic potential in the
      control of chronic bovine mastitis.

PMID- 14672173
TI  - Effect of lipopolysaccharide infusion on serum macromineral and vitamin D
      concentrations in dairy cows.
AB  - Four multiparous lactating cows (175 to 220 d in milk) were used in a 4 x 4 Latin
      square design to assess the effects of four doses (0.0, 0.5, 1.0, 1.5 microg/kg
      of body weight) of lipopolysaccharide (LPS; Escherichia coli 0111:B4) on
      circulating concentrations of macrominerals and vitamin D metabolites. Treatments
      were dissolved in 100 ml of sterile saline and infused intravenously over a
      period of 100 min. Blood was sampled immediately before infusion (0 h), at 60-min
      intervals for 8 h, and at 24 and 48 h postinfusion. Vitamin D metabolites were
      analyzed in samples collected at 0, 2, 6, 24, and 48 h only. Serum Ca and P
      concentrations decreased after LPS infusion, but there was no effect on serum
      magnesium concentration. Plasma 25-OH vitamin D3 and 1,25-(OH)2 vitamin D3 were
      not affected by LPS infusion; however, when analyzed as 0 vs. all other doses of
      LPS combined, there was a tendency for plasma 1,25-(OH)2 vitamin D3 concentration
      to decrease when cows were infused with LPS. The inflammatory response elicited
      by LPS altered plasma macromineral concentrations, a result that may have
      important implications for calcium homeostasis and metabolic health of lactating
      dairy cows.

PMID- 14672175
TI  - Relationship between udder and leg hygiene scores and subclinical mastitis.
AB  - The objective of this study was to determine the relationship between udder and
      leg hygiene scores of lactating dairy cattle and measures of subclinical
      mastitis. Study animals (n = 1250) consisted of lactating dairy cows from eight
      commercial dairy farms. Herds were enrolled during December 2000 and January 2001
      and were visited bimonthly for a total of five visits per herd. Udder and leg
      hygiene scores were recorded by one person using a four-point scale ranging from
      one (very clean) to four (very dirty). Udder and leg hygiene scores were compared
      to bacteriological cultures of milk samples and monthly individual SCC values.
      Mean hygiene scores were 2.09 and 2.33 for udders and legs, respectively. Udder
      hygiene scores (UHS) were significantly associated with leg hygiene scores and
      varied among farms. Linear somatic cell scores increased as udder hygiene score
      increased. Significant differences in somatic cell scores were observed for all
      contrasts of udder hygiene score, except between scores of 1 and 2 and of 3 and
      4. Linear somatic cell scores were associated with leg hygiene scores, but the
      only significant contrast was between leg hygiene scores of 2 and 4. There was a
      significant association between the prevalence of intramammary contagious
      pathogens and udder hygiene score. The prevalence of intramammary environmental
      pathogens was significantly associated with udder hygiene score and was 7.7,
      10.0, 10.6, and 13.5% for UHS of 1, 2, 3, and 4, respectively. The prevalence of
      environmental pathogens was not associated with LHS. Cows with udder hygiene
      scores of 3 and 4 were 1.5 times more likely to have major pathogens isolated
      from milk samples compared with cows with hygiene scores of 1 and 2.

PMID- 14672174
TI  - Effect of lipopolysaccharide on indices of peripheral and hepatic metabolism in
      lactating cows.
AB  - Four multiparous lactating cows (175 to 220 d in milk [DIM]) were used in a 4 x 4
      Latin square design to assess the effects of four doses (0.0, 0.5, 1.0, and 1.5
      microg/kg of body weight) of lipopolysaccharide (LPS; Escherichia coli 0111:B4)
      on performance and plasma metabolite and hormone concentrations. In addition,
      effects of immune activation on in vitro hepatic metabolic capacity were
      evaluated in 12 multiparous lactating cows (150 to 220 DIM) infused with 0 (n =
      6), 1.0 (n = 4) or 2.0 (n = 2) microg of LPS/kg. Milk production and DMI
      decreased linearly with LPS dose for 24 h after LPS infusion. Overall mean plasma
      tumor necrosis factor-alpha, insulin, glucagon, and cortisol concentrations
      increased linearly with LPS dose, and plasma beta-hydroxybutyrate decreased
      linearly by dose after LPS infusion. Infusion of LPS decreased the
      insulin:glucagon molar ratio, but did not affect plasma concentrations of growth
      hormone, insulin-like growth factor-1, leptin, or L-(+)-lactate. Plasma
      concentrations of glucose tended to increase initially and subsequently decrease,
      and there was a quadratic tendency for increased plasma nonesterified fatty acid
      concentrations after LPS administration. In vitro hepatic capacity for conversion
      of [1-(14)C]L-(+)-lactate and [1-(14)C]palmitate, but not [1-(14)C]propionate or
      [1-(14)C]L-alanine, to CO2 increased after LPS administration. Hepatic capacity
      to convert [1-(14)C]propionate to glucose tended to increase, but neither
      esterification nor the conversion of palmitate to acid soluble products was
      altered by LPS. The LPS infusion resulted in significant changes of endocrine
      mediators responsible for regulation of energy metabolism of lactating cows and
      tended to alter subsequent in vitro hepatic metabolic capacity.

PMID- 14672176
TI  - Results of milk samples submitted for microbiological examination in Wisconsin
      from 1994 to 2001.
AB  - The objective of this study was to examine the characteristics of milk samples
      submitted for microbiological examination at the Wisconsin Veterinary Diagnostic
      Laboratory between 1994 and 2001. Results (n = 83,650) of microbiological testing
      of milk samples (n = 77,172) submitted to the Wisconsin Veterinary Diagnostic
      Laboratory from January 1994 until June 2001 were analyzed. Submissions included
      milk samples obtained from cases of clinical and subclinical mastitis as well as
      samples obtained for mastitis surveillance programs. Results were recorded as no
      growth, contaminated, or identified as specific bacterial pathogens. Statistical
      analysis was performed to determine trends in the isolation of mastitis
      pathogens. The proportion of samples identified as contaminated decreased from
      20.6 (1997) to 9.5% (2001). The proportion of samples coded as no growth
      increased from 22.6 (1994) to 49.7% (2001). Isolation of Staphylococcus aureus
      decreased from 17.7% (1994) of isolates to 9.7% (2001), while isolation of
      Streptococcus agalactiae decreased from 8.1 (1994) to 3.0% (2001). Coagulase
      negative Staphylococcus spp. were isolated from 12.7 to 17.5%, environmental
      Streptococcus spp. were isolated from 11.6 to 20.1%, and Escherichia coli were
      isolated from 3.1 to 6.7% of all isolates. No growth and contaminated samples
      comprised almost 50% of total submissions, and it is important that producers
      have proper expectations when submitting milk samples. The proportion of isolates
      identified as Staph. aureus and Strep. agalactiae decreased, suggesting the
      proportion of contagious bacteria causing mastitis has decreased. Environmental
      and contagious pathogens demonstrated characteristic differences by season.

PMID- 14672177
TI  - Identification and characterization of location decision factors for relocating
      dairy farms.
AB  - A survey was conducted to determine the importance of various location factors
      during the site selection process for relocating dairy farms. The objectives were
      to identify the importance of location decision factors (LDF) and characterize
      how importance differs among respondents with different demographic
      characteristics. Information was collected from sampled populations of Grade A
      milk producers in the top 35 milk-producing states in the United States and from
      U.S. agribusiness professionals using a mailed questionnaire. Location decision
      factors (n = 110) were rated on importance using a numerical scale of 0 to 10,
      where 0 = not important and 10 = critically important. Demographic data were
      collected from each respondent. Of 906 respondents, 72.4% identified their
      primary occupation as dairy producer. The five overall most important LDF were 1)
      availability of fresh water supplies (9.16 +/- 0.05); 2) availability of land for
      waste management (8.94 +/- 0.05); 3) average mailbox price of milk (8.79 +/-
      0.05); 4) quality of fresh water supply (8.41 +/- 0.06); and 5) complexity of
      laws governing waste management (8.35 +/- 0.06). Factors pertaining to dairy
      production activities, such as cost of feeds and milk handling, were prevalent
      among those LDF in the upper quartile of importance. Region and herd size had
      significant effects on the overall importance of LDF. The relative importance of
      factors differed between western and eastern regions of the United States.
      Observed differences in importance of LDF among subclasses of respondents suggest
      that characteristics of the geographic regions evaluated and dairy production
      activities at various scales affect perceived importance of certain LDF.

PMID- 14672178
TI  - Milk leakage--an increased risk in automatic milking systems.
AB  - Milk leakage (ML), or milk observed dripping or flowing from one or more teats
      between milkings, has been associated with increased risk of udder infections and
      mastitis in dairy cows. Preliminary observations indicate that ML might occur
      more often in automatic milking systems (AMS) than in conventional milking
      systems (CMS), but comparative data on the incidence of ML in AMS or in CMS are
      not available. Therefore, the occurrence of ML at various observation periods was
      studied in one AMS with cows housed in a free-stall barn in comparison to CMS
      with cows housed either in a free-stall barn or a tie-stall barn and milked at
      regular intervals in a herringbone milking parlor. Relationships between ML and
      other cow and management factors were also examined. In each of 2 yr, all cows (n
      = 230 total; 46 cows present both years) were observed at 2-h intervals during
      six 24-h periods. At least one ML occurred in 39.0 (AMS) vs. 11.2% (CMS) of
      individual cows and in 16.2 (AMS) vs. 2.9% (CMS) of 24-h cow days studied. Milk
      leakage was not related to milk production, parity, stage of lactation, or
      estrous status. However, in the AMS, 62% of primiparous and 28% of multiparous
      cows leaked milk at least once. Milk leakage occurred more often in rear than in
      forequarters. Cows were usually lying down when ML was observed, but intervals
      from previous milking varied, especially in AMS. In AMS, about one-fifth of the
      ML observations occurred < or = 4 h after milking, and half of those were
      associated with disturbances at the previous milking. Milk flow rate was higher
      in quarters leaking milk than in other quarters. Strategies to reduce milk
      leakage in AMS may be important to minimize potential risks of udder disease.

PMID- 14672179
TI  - Ovarian follicular activity in lactating Holstein cows supplemented with
      monensin.
AB  - The objective of this study was to determine effects of monensin on ovarian
      follicular development and reproductive performance in postpartum dairy cows.
      Forty-eight multiparous Holstein cows were randomly assigned to receive either a
      control total mixed ration (n = 24) or the same diet plus 22 mg of monensin/kg (n
      = 24) from 21 d before anticipated calving until cows were either confirmed
      pregnant or were >180 d postpartum. Monensin had no effect on development of the
      first dominant follicle postpartum or the numbers of class 1 (3 to 5 mm), 2 (6 to
      9 mm), or 3 (10 to 15 mm) follicles. Control cows had more class 4 (>15 mm)
      follicles at 10 to 13 d postpartum than cows in the monensin group. The first
      dominant follicle postpartum ovulated, regressed, or became cystic unrelated to
      differences between diets. However, the first ovulation postpartum occurred
      earlier in monensin-fed cows than in the control group (27.2 +/- 2.1 d vs. 32.4
      +/- 1.5 d), with no dietary effects on the diameter of the ovulating follicle.
      Similarly, treatments did not differ in the proportion of cows with 2 or 3 waves
      of ovarian follicular development per cycle, nor in the number of follicles of
      all classes during the breeding period. Times of ovulation following treatment
      with prostaglandin F2alpha were not different between dietary groups. Pregnancy
      rates after timed artificial insemination were similar between diets.
      Supplementation with monensin resulted in a shorter postpartum interval to first
      ovulation but did not affect other reproductive measures in healthy, lactating
      dairy cows.

PMID- 14672180
TI  - Demonstration of a role for insulin in the regulation of leptin in lactating
      dairy cows.
AB  - In lactating dairy cows, the onset of negative net energy balance (EB) at
      parturition causes a reduction in plasma leptin and is also associated with
      increased concentration of growth hormone (GH) and decreased concentration of
      insulin. These observations raise the possibility that opposite changes in plasma
      insulin and GH are partly responsible for reduced plasma leptin. To test this
      hypothesis, we first examined the effects of undernutrition without the
      confounding influence of parturition by using late lactating dairy cows fed 120%
      of their nutrient requirements or restricted to 33% of maintenance requirements.
      Plasma leptin was reduced within 24 h of feed restriction, and was associated
      with increased plasma GH and decreased plasma insulin. Complete food deprivation
      for 48 h caused similar changes in the plasma concentration of leptin. To
      determine if an elevation in GH is responsible for the fall in plasma leptin,
      dairy cows were treated with excipient or bovine somatotropin in early lactation
      or in late lactation. Growth hormone treatment had no significant effect on
      plasma leptin irrespective of stage of lactation. Finally, the effects of insulin
      were studied by performing euglycemic hyperinsulinemic clamps in mid-lactating
      dairy cows. After 96 h of hyperinsulinemia, plasma leptin was increased
      significantly. These data indicate that insulin regulates plasma leptin in
      lactating dairy cows. They also suggest that, in undernourished lactating dairy
      cows, reduced plasma insulin could account for a portion of the decline in plasma
      leptin but that elevated plasma GH is unlikely to have a major effect.

PMID- 14672181
TI  - Economic value of timely determination of unexpected decreases in detection of
      estrus using control charts.
AB  - Total economic effects of decreased estrus detection efficiency (EDE) are a
      function of the economic loss per day and the length of the decrease. A
      stochastic dynamic dairy herd simulation model was used to determine whether
      estimates from permanently different EDE rates in herds of 100 and 1000 cows
      could approximate net returns due to temporary decreases in EDE. The default EDE
      was 65% and was either permanently or temporarily decreased to 55, 45, or 35%.
      Temporary decreases in EDE were assumed to continue until identified using
      cumulative sum or Shewhart control charts. Marginal changes in net return were
      greater at lower permanent rates of EDE, with losses ranging from 0.73 to 1.24
      dollars per extra day open. Temporary decreases in EDE typically yielded smaller
      effects on net return than permanent decreases, but estimates were not
      consistently significantly different. However, temporary (30 to 960 d) decreases
      in EDE affected projected herd economic performance for several years after EDE
      was reset to 65%. Total losses in net return due to temporary decreases in EDE
      ranged from 4.44 dollars (accepting more false alarms) to 12.53 dollars (fewer
      false alarms) per cow for the 100-cow herd. For the 1000-cow herd, total losses
      in net return ranged from 0.95 to 10.43 dollars per cow. Total losses were not
      dependent on magnitude of decreased EDE because lower EDE could be detected
      earlier, thereby compensating for higher daily losses; for example, 35% EDE
      resulted in lower total losses than 55% EDE. Decreases to 55% EDE were detected
      sooner by cumulative sum charts, whereas decreases to 35% EDE were detected
      earlier by Shewhart charts. Both control charts used together can identify
      unexpected decreases in EDE more efficiently, thereby minimizing potential
      economic losses.

PMID- 14672182
TI  - Effects of supplemental energy on metabolic and immune measurements in
      periparturient dairy cows with Johne's disease.
AB  - The present study was designed to evaluate whether feeding supplemental energy
      would improve the metabolic profile and alleviate some of the immunosuppression
      typically noted during the periparturient period in dairy cows with Johne's
      disease. Twelve dairy cows naturally infected with Mycobacterium paratuberculosis
      were fitted with rumen cannulas in late gestation and assigned to treatment
      groups: control, n = 6; or stuffed, n = 6. Cows in the control group were allowed
      to consume feed ad libitum. Cows assigned to the stuffed treatment group were
      also fed ad libitum but received additional total mixed rations by manually
      stuffing their rumens with refused feed to maintain dry matter intake of 2% body
      weight per day before calving and 2.5% body weight per day after calving. Serum
      nonesterified fatty acid levels were significantly decreased in stuffed cows
      compared with control cows, indicating that stuffing to maintain dry matter
      intake improved the energy balance in the cows. In addition, periparturient serum
      calcium and magnesium concentrations were significantly higher in stuffed cows.
      Stuffing modulated cell-mediated immunity by reducing lymphocyte proliferative
      responses to T-cell mitogens during early lactation. Stuffing resulted in an
      increase in the secretion of in vitro immunoglobulin by peripheral blood
      mononuclear cells after parturition when compared to control cows. These data
      demonstrate that energy balance is improved by providing additional energy in
      this manner and suggest energy supplementation can improve some aspects of immune
      function during the periparturient period.

PMID- 14672183
TI  - Prediction of dairy housing construction costs.
AB  - Dairy farms in Galicia and elsewhere in Europe are going through a transition
      phase to adapt to modern dairy technology, improve labor efficiency, and increase
      in size and scale. Expanding a dairy herd and building housing for more cows can
      be very expensive. A poor decision during expansion can result in serious
      financial difficulties even to the point of making the farm economically
      unviable. Dairy managers must carefully evaluate existing alternatives and must
      select an optimal strategy. To aid this decision, a computer spreadsheet
      application has been developed that predicts the cost per cow and cost per unit
      of area of alternative designs as functions of the number of cows to be housed.
      The spreadsheet is, in principle, applicable to a wide variety of designs and to
      housing for livestock other than dairy cattle. However, the current database
      allows comparison among six of the dairy housing designs that have been used most
      widely in Galicia in recent years. From projected financial results of the
      developed model, it was concluded that differing designs were preferred for
      different farm circumstances. Preferred designs for farms with 60 to 200 cows
      were either four rows of facing free stalls or four rows of tail-to-tail free
      stalls, which have virtually the same costs. Whereas for farms with fewer than 60
      cows, the preferred design was two rows of tail-to-tail free stalls, designs with
      three rows of free stalls were generally more costly per cow. Results of design
      calculations must be integrated with other farm management considerations in
      choosing a particular design.

PMID- 14672184
TI  - Pelleted beet pulp substituted for high-moisture corn: 1. Effects on feed intake,
      chewing behavior, and milk production of lactating dairy cows.
AB  - The effects of increasing concentrations of dried, pelleted beet pulp substituted
      for high-moisture corn on intake, milk production, and chewing behavior were
      evaluated using eight ruminally and duodenally cannulated multiparous Holstein
      cows in a duplicated 4 x 4 Latin square design with 21-d periods. Cows were 79 +/
      17 (mean +/- SD) d in milk at the beginning of the experiment. Experimental
      diets with 40% forage (corn silage and alfalfa silage) and 60% concentrate
      contained 0, 6.1, 12.1, or 24.3% beet pulp substituted for high-moisture corn on
      a dry matter basis. Diet concentrations of neutral detergent fiber (NDF) and
      starch were 24.3 and 34.6% (0% beet pulp), 26.2 and 30.5% (6% beet pulp), 28.0
      and 26.5% (12% beet pulp), and 31.6 and 18.4% (24% beet pulp), respectively.
      Increasing beet pulp in the diet caused a linear decrease in dry matter intake
      (DMI). Time spent eating per day and per kilogram of DMI increased, and sorting
      against NDF tended to increase, with added beet pulp. Substituting beet pulp for
      corn caused a quadratic response in milk fat yield, with the highest yield for
      the 6% beet pulp treatment. A tendency was detected for a similar quadratic
      response in 3.5% fat-corrected milk yield. Lower plasma insulin concentration may
      have resulted in lower body condition gain for cows fed diets with higher beet
      pulp concentration. Partial substitution of pelleted beet pulp for high-moisture
      corn decreased intake but also may have permitted greater fat-corrected milk
      yield.

PMID- 14672185
TI  - Pelleted beet pulp substituted for high-moisture corn: 2. Effects on digestion
      and ruminal digestion kinetics in lactating dairy cows.
AB  - The effects of increasing concentrations of dried, pelleted beet pulp substituted
      for high-moisture corn on digestion and ruminal digestion kinetics were evaluated
      using eight ruminally and duodenally cannulated multiparous Holstein cows in a
      duplicated 4 x 4 Latin square design with 21-d periods. Cows were 79 +/- 17 (mean
      +/- SD) d in milk at the beginning of the experiment. Experimental diets with 40%
      forage (corn silage and alfalfa silage) and 60% concentrate contained 0, 6.1,
      12.1, or 24.3% beet pulp substituted for high-moisture corn on a dry matter
      basis. Diet concentrations of neutral detergent fiber (NDF) and starch were 24.3
      and 34.6% (0% beet pulp), 26.2 and 30.5% (6% beet pulp), 28.0 and 26.5% (12% beet
      pulp), and 31.6 and 18.4% (24% beet pulp), respectively. Ruminal dry matter pool
      decreased and NDF turnover rate increased as dietary beet pulp content increased.
      Potentially digestible NDF was digested more extensively and at a faster rate in
      the rumen with increasing beet pulp, resulting in increased total tract NDF
      digestibility. Passage rates of potentially digestible NDF and of indigestible
      NDF were not affected by treatment. True ruminal digestibility of starch
      decreased with increasing beet pulp substitution. This was caused by a linear
      increase in starch passage rate, possibly because of increasing ruminal fill, and
      a linear decrease in digestion rate of starch in the rumen, possibly because of
      reduced amylolytic enzyme activity for lower-starch diets. Although true ruminal
      starch digestibility decreased when more beet pulp was fed, whole tract starch
      digestibility was not affected because of compensatory digestion of starch in the
      intestines. Due to more thorough digestion of fiber in diets containing more beet
      pulp, whole-tract digestibility of organic matter increased linearly, and intake
      of digestible organic matter was not affected. Partially replacing high-moisture
      corn with beet pulp in low-forage diets increased fiber digestibility without
      reducing whole-tract starch digestibility.

PMID- 14672186
TI  - Pelleted beet pulp substituted for high-moisture corn: 3. Effects on ruminal
      fermentation, pH, and microbial protein efficiency in lactating dairy cows.
AB  - The effects of increasing concentrations of dried, pelleted beet pulp substituted
      for high-moisture corn on ruminal fermentation, pH, and microbial efficiency were
      evaluated using eight ruminally and duodenally cannulated multiparous Holstein
      cows in a duplicated 4 x 4 Latin square design with 21-d periods. Cows were 79 +/
      17 (mean +/- SD) DIM at the beginning of the experiment. Experimental diets with
      40% forage (corn silage and alfalfa silage) and 60% concentrate contained 0, 6.1,
      12.1, or 24.3% beet pulp substituted for high-moisture corn on a DM basis. Diet
      concentrations of NDF and starch were 24.3 and 34.6% (0% beet pulp), 26.2 and
      30.5% (6% beet pulp), 28.0, and 26.5% (12% beet pulp), and 31.6 and 18.4% (24%
      beet pulp), respectively. Substituting beet pulp for corn did not affect daily
      mean or minimum ruminal pH but tended to reduce pH range. Ruminal
      acetate:propionate responded in a positive exponential relationship to added beet
      pulp. Rate of valerate absorption from the rumen was not affected by treatment.
      Substituting beet pulp for corn up to 24% of diet DM did not affect efficiency of
      ruminal microbial protein production, expressed as microbial N flow to the
      duodenum as a percentage of OM truly digested in the rumen. Microbial efficiency
      was not correlated to mean pH or daily minimum pH. While microbial efficiency was
      not directly related to concentration of beet pulp fed, it was positively
      correlated with passage rate of particulate matter, as represented by starch and
      indigestible NDF, probably due to reduced turnover of microbial protein in the
      rumen.

PMID- 14672187
TI  - Technical note: Validation of a system for monitoring feeding behavior of dairy
      cows.
AB  - An electronic system has been designed that allows for passive monitoring of
      feeding behavior of individual cows housed in a free-stall barn. The objective of
      this study was to validate the data generated by this GrowSafe feed alley
      monitoring system. Twelve lactating cows were each monitored for 24 h using both
      the GrowSafe system and time-lapse video. The GrowSafe estimation of number of
      meals consumed by each cow showed perfect agreement with meal frequency
      identified using the video recordings. The duration of these meals, as estimated
      by GrowSafe, was highly correlated with the meal duration derived from the video
      (R2 = 0.98). Despite the excellent agreement for these meal-based measures, for
      each cow we found some instances in which the video showed that a cow was present
      at the feed alley but GrowSafe failed to detect cow presence (12.6% of
      observations) and a few instances in which the reverse was true (3.5% of
      observations). However, all the missed or extraneous data from the GrowSafe
      system were closely associated in time with known periods of feeding. These
      results indicate that this feed alley monitoring system can provide very good
      measures of meal frequency and meal duration and reasonable estimates of
      instantaneous feed alley attendance for loose-housed dairy cattle.

PMID- 14672188
TI  - The effect of Lactobacillus buchneri and Lactobacillus plantarum on the
      fermentation, aerobic stability, and ruminal degradability of low dry matter corn
      and sorghum silages.
AB  - The effect of Lactobacillus buchneri, alone or in combination with Lactobacillus
      plantarum, on the fermentation, aerobic stability, and ruminal degradability of
      low dry matter corn and sorghum silages was studied under laboratory conditions.
      The inoculants were applied at 1 x 10(6) cfu/g. Silages with no additives served
      as control. After treatment, the chopped forages were ensiled in 1.5-L anaerobic
      jars. Three jars per treatment were sampled on d 2, 4, 8, 15, and 90. After 90 d
      of storage, the silages were subjected to an aerobic stability test lasting 5 d,
      in which CO2 production, as well as chemical and microbiological parameters, was
      measured to determine the extent of aerobic deterioration. At the end of the
      ensiling period (d 90), the L. buchneri- and L. buchneri + L. plantarum
      inoculated silages had significantly higher levels of acetic acid than the
      control and L. plantarum-inoculated silages. Therefore, yeast activity was
      impaired in the L. buchneri- and L. buchneri + L. plantarum-inoculated silages.
      As a result, L. buchneri, alone or in combination with L. plantarum, improved
      aerobic stability of the low dry matter corn and sorghum silages. The combination
      of L. buchneri and L. plantarum reduced ammonia N concentrations and fermentation
      losses in the silages compared with L. buchneri alone. However, L. buchneri, L.
      plantarum, and a combination of L. buchneri + L. plantarum did not effect in situ
      rumen dry matter, organic matters, or neutral detergent fiber degradability of
      the silages. The L. buchneri was very effective in protecting the low dry matter
      corn and sorghum silages exposed to air under laboratory conditions. The use of
      L. buchneri, alone or in combination with L. plantarum, as a silage inoculant can
      improve the aerobic stability of low dry matter corn and sorghum silages by
      inhibition of yeast activity.

PMID- 14672189
TI  - Effect of dietary fat and vitamin E on alpha-tocopherol in milk from dairy cows.
AB  - Diets with different fat treatments and with 25, 125, or 250 IU of supplemental
      vitamin E (all-rac alpha-tocopheryl acetate)/kg of dry matter (DM) were fed for
      28 d to midlactation Holstein cows to determine factors affecting concentrations
      of alpha-tocopherol in milk. Diets contained no supplemental fat or 2.25% added
      fat from roasted soybeans or tallow. Vitamin E treatment had no effects on
      production, but fat supplementation increased milk yield (37.2 vs. 35.1 kg/d).
      Cows fed RSB ate more DM (24.0 vs. 21.9 kg/d) and produced more milk fat than
      cows fed tallow. Supplemental fat increased plasma concentrations of alpha
      tocopherol and cholesterol. Increased intake of alpha-tocopherol linearly
      increased concentrations of alpha-tocopherol in plasma but the rate of increase
      was 1.9 times greater when fat was fed. Plasma alpha-tocopherol concentrations
      were linearly related to concentrations in milk, but a change in plasma alpha
      tocopherol resulted in a smaller change in milk alpha-tocopherol when fat was fed
      than when it was not. Fat treatment did not affect plasma alpha-tocopherol
      expressed relative to plasma cholesterol (mg alpha-tocopherol/g cholesterol) or
      relationships between plasma alpha-tocopherol/g of cholesterol and milk alpha
      tocopherol. These data suggest that concentrations of alpha-tocopherol in milk
      are a function of the alpha-tocopherol enrichment of the plasma lipid fraction
      and enrichment of that fraction is saturable.

PMID- 14672190
TI  - Composition and functional capacity of blood mononuclear leukocyte populations
      from neonatal calves on standard and intensified milk replacer diets.
AB  - Effects of increased dietary energy and protein on the composition and functional
      capacities of blood mononuclear leukocyte populations from milk replacer-fed
      calves were investigated. Holstein bull calves (average age: 4.2 d; n = 19) were
      assigned randomly to one of two treatment groups. Treatment 1 calves (n = 9) were
      fed a 20% crude protein, 20% fat milk replacer at a rate of 1.4% body weight of
      dry matter/d for 8 wk, whereas treatment 2 calves (n = 10) were fed a 30% crude
      protein, 20% fat milk replacer at a rate of 2.5% body weight of dry matter per
      day. Composition and functional capacities of mononuclear leukocyte populations
      from blood samples collected at 4, 18, 32, 46, and 60 d of age were characterized
      by flow cytometry and ex vivo cell function assays. From 11 to 60 d of age, the
      mean daily weight gain of treatment 2 calves (1.20 kg/d) was greater than daily
      weight gain of treatment 1 calves (0.55 kg/d). At 60 d of age, the mean body
      weight of treatment two calves was 53% (39 kg) greater than the mean body weight
      of treatment 1 calves. Total numbers of blood leukocytes and the composition of
      the mononuclear leukocyte population were unaffected by the plane of nutrition.
      Mitogen-induced DNA-synthesis and immunoglobulin M secretion also were unaffected
      by dietary treatment. Blood mononuclear leukocytes from calves on intensified
      diets, however, produced less interferon-gamma and more inducible nitric oxide,
      suggesting that increased dietary energy and protein affects specific aspects of
      leukocyte function associated with cell-mediated immunity. The impact of altered
      interferon-gamma and NO production on the calf s susceptibility to infectious
      disease are not known. Mononuclear leukocyte populations from all calves also
      demonstrated age-related changes in composition and functional capacity, likely
      reflecting natural exposure to infectious agents and maturation of the calfs
      immune system.

PMID- 14672191
TI  - Effects of body surface area estimates on predicted energy requirements and heat
      stress.
AB  - The 0.09 x W(0.67) equation (where W = weight in kilograms) used to estimate body
      surface area (SA) in cattle energy requirements models was developed using
      measurements of sheep that weighed between 24 and 38 kg. The SA estimates it
      produced were compared with those of the equation 0.14 x W(0.57), based on
      Holstein cattle weighing 41 to 617 kg. The estimate of SA produced by the first
      equation was 23% greater for a 650-kg cow than that obtained by the second
      equation. The impact of SA estimates on thermal comfort range and development of
      cold and heat stress effects was calculated, using a thermal balance model, for a
      600-kg cow producing 35 kg/d. Predicted metabolic heat production increment at 
      10 degrees C ambient temperature with 0.5 m/s wind velocity was 0.44 Mcal/d and
      1.21 Mcal/d by the first and second equation, respectively. Predicted lower
      critical temperature (LCT) was -8.7 degrees C by the first equation and -0.6
      degrees C by the second equation, an 8 degrees C difference. The LCT difference
      between SA estimates increased from 4.6 to 9.4 degrees C, with milk production
      rising from 10 to 45 kg/d. By the first equation, skin nonevaporative heat loss
      started to decrease at 15 degrees C and became close to nil at and ambient
      temperature of 35 degrees C, whereas by the second equation, respective values
      were 10 degrees C and 39 degrees C, a 5 degrees C shift in the estimated
      temperature at which thermal stress would start developing. The larger SA and
      skin water loss predicted by the first equation reduced by 50% the respiratory
      heat loss involved in maintenance of thermal balance at higher temperatures for a
      600-kg cow. The second equation seems preferable for Holstein SA estimation since
      it is based on Holstein cattle data. It provides more adequate estimates of
      energy requirement in the cold and of heat stress relief needs for Holstein
      cattle.

PMID- 14672192
TI  - Effects of replacing chopped alfalfa hay with alfalfa silage in a total mixed
      ration on production and rumen conditions of lactating dairy cows.
AB  - The effects of replacing chopped alfalfa hay with alfalfa silage in a total mixed
      ration containing barley grain and corn silage on production and rumen conditions
      were investigated. Cows received three diets that all contained (dry matter
      basis) 38.5% barley grain-based energy supplement, 30.5% corn silage, 17.0%
      protein supplement, and 4.2% sunflower seeds. One diet contained (dry matter
      basis) 9.8% of chopped alfalfa hay and no alfalfa silage. One diet contained (dry
      matter basis) 4.9% chopped alfalfa hay and 4.9% alfalfa silage. One diet
      contained (dry matter basis) 9.8% of alfalfa silage and no chopped alfalfa hay.
      Contents of crude protein, neutral detergent fiber, acid detergent fiber, and
      starch, averaged across diets, were 16.7, 41.3, 21.1, and 24.4% DM, respectively,
      and did not differ significantly among diets. Replacing chopped alfalfa hay with
      alfalfa silage decreased the proportion of dietary DM passing through the 8-mm
      screen of the Penn State Particle Separator from 61.9 to 55.2% dry matter and
      significantly increased dietary physical effective NDF (peNDF) content,
      calculated as the NDF retained by the two screens of the Penn State Particle
      Separator, from 20.1 to 23.3% DM. Replacing chopped alfalfa hay with alfalfa
      silage also reduced dietary DM content, increased rumen pH from 6.27 to 6.47,
      reduced volatile fatty acid concentrations, numerically increased milk fat
      concentration and milk fat yield. Milk yield, milk protein concentration, dry
      matter intake, and rumen ammonia concentration were not affected.

PMID- 14672193
TI  - Rates of production of acetate, propionate, and butyrate in the rumen of
      lactating dairy cows given normal and low-roughage diets.
AB  - Five lactating dairy cows with a permanent cannula in the rumen were given (kg
      DM/d) a normal diet (7.8 concentrates, 5.1 hay) or a low-roughage (LR) diet (11.5
      concentrates, 1.2 hay) in two meals daily in a two-period crossover design. Milk
      fat (g/kg) was severely reduced on diet LR. To measure rates of production of
      individual volatile fatty acids (VFA) in the rumen, 0.5 mCi 1-(14)C-acetic acid,
      2-(14)C-propionic acid, or 1-(14)C-n-butyric acid were infused into the rumen for
      22 h at intervals of 2 to 6 d; rumen samples were taken over the last 12 h. To
      measure rumen volume, we infused Cr-EDTA into the rumen continuously, and
      polyethylene glycol was injected 2 h before the morning feed. Results were very
      variable, so volumes measured by rumen emptying were used instead. Net production
      of propionic acid more than doubled on LR, but acetate and butyrate production
      was only numerically lower. Net production rates pooled across both diets were
      significantly related to concentrations for each VFA. Molar proportions of net
      production were only slightly higher than molar proportions of concentrations for
      acetate and propionate but were lower for butyrate. The net energy value (MJ/d)
      of production of the three VFA increased from 89.5 on normal to 109.1 on LR,
      equivalent to 55 and 64% of digestible energy, respectively. Fully interchanging,
      three-pool models of VFA C fluxes are presented. It is concluded that net
      production rates of VFA can be measured in non-steady states without the need to
      measure rumen volumes.

PMID- 14672194
TI  - Adaptations in body muscle and fat in transition dairy cattle fed differing
      amounts of protein and methionine hydroxy analog.
AB  - The objectives were to determine effects of prepartum protein intake and dietary
      amino acid balance on production, adaptations in body fat and protein, amino acid
      concentrations, and, indirectly, body protein breakdown in early lactation.
      Multiparous Holstein cows (n = 42) were fed diets containing 11 or 14% crude
      protein with or without 20 g/d of methionine hydroxy analog for 21 d prepartum
      and then fed a common diet of 17% crude protein for 120 d postpartum, with or
      without 50 g/d of methionine hydroxy analog. Dry matter intake postpartum
      averaged 25.4 kg and milk production 41.6 kg. Cows fed the 14% CP diet ate 0.7 kg
      more dry matter and gave 1.7 kg more milk than those fed the 11% diet postpartum,
      but this difference was not significant. Cows fed methionine hydroxy analog
      prepartum lost less body protein from -14 to 60 d in milk. From d 60 to 120, body
      fat increased 8.5 and 11.5 kg for low and high protein groups and body protein
      increased 0.5 and 1.0 kg. Serum concentrations of branched chain amino acids fell
      17% in the first few weeks postpartum, lysine fell 15%, histidine fell 16%,
      methionine increased 20%, and cysteine increased 30%. The ratio of serum 3
      methylhistidine to creatinine was determined to indicate muscle protein
      degradation. An increase in this ratio at 7 d postpartum indicated increased body
      protein breakdown, there was no effect of prepartum ration. Increased protein
      intake prepartum may allow more feed intake and milk production postpartum, and
      supplementing a methionine analog on a ration already balanced in methionine by
      contemporary models may spare body protein.

PMID- 14672195
TI  - Conjugated linoleic acid and vaccenic acid in rumen, plasma, and milk of cows fed
      fish oil and fats differing in saturation of 18 carbon fatty acids.
AB  - The objective of this study was to examine the effect of feeding fish oil (FO)
      along with fat sources that varied in saturation of 18 carbon fatty acids (high
      stearic, high oleic, high linoleic, or high linolenic acids) on rumen, plasma,
      and milk fatty acid profiles. Four primiparous Holstein cows at 85 d in milk (+/-
      40) were assigned to 4 x 4 Latin squares with 4-wk periods. Treatment diets were
      1) 1% FO plus 2% commercial fat high in stearic acid (HS); 2) 1% FO plus 2% fat
      from high oleic acid sunflower seeds (HO); 3) 1% FO plus 2% fat from high
      linoleic acid sunflower seeds (HLO); and 4) 1% FO plus 2% fat from flax seeds
      (high linolenic; HLN). Diets were formulated to contain 18% crude protein and
      were composed of 50% (dry basis) concentrate mix, 25% corn silage, 12.5% alfalfa
      silage, and 12.5% alfalfa hay. Milk production, milk protein percentages and
      yields, and dry matter intake were similar across diets. Milk fat concentrations
      and yields were least for HO and HLO diets. The proportion of milk cis-9, trans
      11 conjugated linoleic acid (CLA; 0.71, 0.99, 1.71, and 1.12 g/100 g fatty acids,
      respectively), and vaccenic acid (TVA; 1.85, 2.60, 4.14, and 2.16 g/100 g fatty
      acids, respectively) were greatest with the HLO diet. The proportions of ruminal
      cis-9, trans-11 CLA (0.09, 0.16, 0.18, and 0.16 g/100 g fatty acids,
      respectively) were similar for the HO, HLO, and HLN diets and all were higher
      than for the HS diet. The proportions of TVA (2.85, 4.36, 8.69, and 4.64 g/100 g
      fatty acids, respectively) increased with the HO, HLO, and HLN diets compared
      with the HS diets, and the increase was greatest with the HLO diet. The effects
      of fat supplements on ruminal TVA concentrations were also reflected in plasma
      triglycerides, (2.75, 4.64, 8.77, and 5.42 g/100 g fatty acids, respectively);
      however, there were no differences in the proportion of cis-9, trans-11 CLA
      (0.06, 0.07, 0.06, and 0.07 g/100 g fatty acids, respectively). This study
      further supports the significant role for mammary delta-9 desaturase in milk cis
      9, trans-11 CLA production.

PMID- 14672196
TI  - Ruminal fermentation and bacterial protein synthesis of whole cottonseed coated
      with combinations of gelatinized corn starch and urea.
AB  - Four ruminally and duodenally cannulated Jersey cows were used in a 4 x 5
      incomplete Latin square study to determine the effects of including urea in the
      gelatinized corn starch coating applied to whole cottonseed (WCS) on ruminal
      fermentation, fiber digestion, and bacterial protein synthesis. Treatments
      included uncoated WCS (control) and four coated WCS treatments. The coatings
      provided two concentrations each of gelatinized corn starch (2.5 [2S] or 5% [5S])
      and feed grade urea (0.25 [2U] or 0.5% [5U]). Treated WCS comprised 15% of the
      ration dry matter that was fed as a total mixed ration once daily. Ruminal pH and
      molar proportions of isobutyrate was higher and NH3-N concentrations lower for
      control compared with coated WCS. Molar proportions of propionate tended to be
      higher and valerate was lower with 2S compared with 5S. Molar proportions of
      acetate tended to be lower, whereas butyrate was higher for 5U than 2U. Nutrient
      intake was lower for WCS coated with 5S5U compared with 2S5U. Ruminal NDF
      digestibility of NDF tended to be higher with 5U compared with 2U, but no
      differences were observed in ruminal or total tract apparent digestibility of
      nutrients. No differences were observed in the flow of total N or bacterial N to
      the duodenum, but the flow of nonbacterial N tended to be higher for WCS coated
      with 5U. Coating WCS appears to slightly alter ruminal metabolism while providing
      similar amounts of N flowing to the duodenum without altering fiber digestion.

PMID- 14672197
TI  - Effects of corn silage hybrid and dietary concentration of forage NDF on
      digestibility and performance by dairy cows.
AB  - Eight intact multiparous cows and four ruminally and duodenally cannulated
      primiparous cows were fed four diets in a replicated 4 x 4 Latin square design:
      1) 17% forage neutral detergent fiber (NDF) with brown midrib corn silage
      (BMRCS), 2) 21% forage NDF with BMRCS, 3) 17% forage NDF with conventional corn
      silage (CCS), and 4) 21% forage NDF with CCS. Diets contained 17.4% crude protein
      and 38.5% NDF. Each period consisted of 4 wk for intact cows and 2 wk for
      cannulated cows. For intact cows, DM intake was higher for BMRCS than CCS, and
      milk urea N was higher for 21 than 17% forage NDF. Milk protein yield tended to
      be higher and milk urea N lower for cows fed BMRCS than those fed CCS. Milk yield
      and milk protein percentage were similar among treatments. For the cannulated
      cows, ruminal mat consistency was similar among treatments. Based on a 72 h in
      situ incubation, BMRCS was lower in indigestible NDF than CCS. The BMRCS resulted
      in a higher proportion of ruminal propionate than CCS. Cows fed 21% forage NDF
      had a higher proportion of acetate and a lower proportion of propionate than cows
      fed 17% forage NDF. The total tract digestibility of nutrients and efficiency of
      bacterial N synthesis were similar among treatments, except that BMRCS resulted
      in lower intestinal fatty acid digestibility than CCS, and 17% forage NDF tended
      to result in higher total tract fatty acid digestibility than 21% forage NDF.
      Ruminal NDF digestibility was similar among dietary treatments. The increased
      milk production observed from feeding BMRCS in some studies may be explained by
      higher DM intake rather than increased total tract digestibility of the diets.

PMID- 14672198
TI  - Effects of corn silage processing and amino acid supplementation on the
      performance of lactating dairy cows.
AB  - This experiment was conducted to determine the effect of crop processing and
      amino acid supplementation on dairy cow performance. Corn silage processed (PCS)
      or unprocessed (UCS) was used as the main forage (45% of dry matter, DM) in a
      total mixed ration (TMR). Each TMR was either supplemented (AA) or not (AAO) with
      ruminally protected amino acids (lysine, 3 g/d and methionine, 14 g/d). Thirty
      two (551 kg) Holstein cows were randomly assigned to four treatments: PCS-AA, PCS
      AA0, UCS-AA, and UCS-AA0 in a 2 x 2 factorial structure. Between wk 7 and 17 of
      lactation, cows were fed ad libitum TMR comprising 45% of corn silage plus 1 kg
      of grass hay once a day. The UCS presented better fermentation characteristics
      than PCS. Dry matter intake (DMI) of the TMR was not affected by treatment and
      averaged 22.7 kg/d. Energy-corrected milk (ECM) production was 9% higher with UCS
      than with PCS (33.1 vs. 30.1 kg/d). Milk efficiency was therefore 6% higher with
      UCS than with PCS (1.43 vs. 1.35 kg ECM/kg of DMI). The concentration of major
      milk constituents (fat, protein, lactose, urea) was not affected by treatments.
      Apparent digestibility of DM, organic matter, N, starch, acid detergent fiber,
      and neutral detergent fiber were similar among treatments. The effective ruminal
      degradability of DM, starch, and protein, however, was greater with PCS than with
      UCS. Amino acid supplementation had no effect on milk production nor on milk
      constituents, whether it was used with processed corn silage or with unprocessed
      corn silage. These data indicate that feeding UCS resulted in a greater milk
      production compared with PCS. The numerically higher DMI, a potentially greater
      intestinal digestion of starch or the better conservation of UCS could have
      contributed to the greater milk production.

PMID- 14672199
TI  - Genetic parameters for body condition score and its relationship with type and
      production traits in Swiss Holsteins.
AB  - The objectives of this study were to estimate the genetic and environmental
      parameters between body condition score (BCS) and 27 conformation and 3
      production traits in Swiss Holstein cattle. The dataset consisted of 31,500 first
      lactation cows, which were daughters of 545 sires in 1867 herds. Bivariate sire
      models with relationships among sires were used to estimate parameters. Least
      squares means for BCS by lactation stage show that cows lose BCS up to 5 mo after
      calving and gain BCS prior to the next calving. Regression models showed that an
      increase in age and percentage of Holstein genes results in an increase and
      decrease in BCS, respectively. Heritability (h2) was 0.24 for BCS score, which
      indicates good potential for selection. Sire estimated breeding values for BCS
      ranged from -0.46 to +0.51 units. Heritabilities ranged from 0.08 (heel depth) to
      0.46 (rump width) for type traits and 0.23 to 0.29 for yield traits. Genetic
      correlations of BCS with 8 conformation traits were significant; stature (0.28),
      heart girth (0.21), strength (0.17), loin (-0.39), body capacity (0.19), dairy
      character (-0.35), udder quality (-0.42), and teat position rear (-0.33). Milk
      production and body condition have an unfavorable genetic correlation (-0.12 to 
      0.17). These results show that selection for good body condition, body
      conformation, and optimal milk production is possible and their genetic
      associations reported here will be useful for designing Swiss breeding goals.

PMID- 14672200
TI  - Detection of mastitis in dairy cattle by use of mixture models for repeated
      somatic cell scores: a Bayesian approach via Gibbs sampling.
AB  - The distribution of somatic cell scores could be regarded as a mixture of at
      least two components depending on a cow's udder health status. A heteroscedastic
      two-component Bayesian normal mixture model with random effects was developed and
      implemented via Gibbs sampling. The model was evaluated using datasets consisting
      of simulated somatic cell score records. Somatic cell score was simulated as a
      mixture representing two alternative udder health statuses ("healthy" or
      "diseased"). Animals were assigned randomly to the two components according to
      the probability of group membership (Pm). Random effects (additive genetic and
      permanent environment), when included, had identical distributions across mixture
      components. Posterior probabilities of putative mastitis were estimated for all
      observations, and model adequacy was evaluated using measures of sensitivity,
      specificity, and posterior probability of misclassification. Fitting different
      residual variances in the two mixture components caused some bias in estimation
      of parameters. When the components were difficult to disentangle, so were their
      residual variances, causing bias in estimation of Pm and of location parameters
      of the two underlying distributions. When all variance components were identical
      across mixture components, the mixture model analyses returned parameter
      estimates essentially without bias and with a high degree of precision. Including
      random effects in the model increased the probability of correct classification
      substantially. No sizable differences in probability of correct classification
      were found between models in which a single cow effect (ignoring relationships)
      was fitted and models where this effect was split into genetic and permanent
      environmental components, utilizing relationship information. When genetic and
      permanent environmental effects were fitted, the between-replicate variance of
      estimates of posterior means was smaller because the model accounted for random
      genetic drift.

PMID- 14672201
TI  - Genetic parameters for body condition score, body weight, milk yield, and
      fertility estimated using random regression models.
AB  - Genetic (co)variances between body condition score (BCS), body weight (BW), milk
      yield, and fertility were estimated using a random regression animal model
      extended to multivariate analysis. The data analyzed included 81,313 BCS
      observations, 91,937 BW observations, and 100,458 milk test-day yields from 8725
      multiparous Holstein-Friesian cows. A cubic random regression was sufficient to
      model the changing genetic variances for BCS, BW, and milk across different days
      in milk. The genetic correlations between BCS and fertility changed little over
      the lactation; genetic correlations between BCS and interval to first service and
      between BCS and pregnancy rate to first service varied from -0.47 to -0.31, and
      from 0.15 to 0.38, respectively. This suggests that maximum genetic gain in
      fertility from indirect selection on BCS should be based on measurements taken in
      midlactation when the genetic variance for BCS is largest. Selection for
      increased BW resulted in shorter intervals to first service, but more services
      and poorer pregnancy rates; genetic correlations between BW and pregnancy rate to
      first service varied from -0.52 to -0.45. Genetic selection for higher lactation
      milk yield alone through selection on increased milk yield in early lactation is
      likely to have a more deleterious effect on genetic merit for fertility than
      selection on higher milk yield in late lactation.

PMID- 14672202
TI  - Seasonality of days open in US Holsteins.
AB  - The objectives of this study were to establish a pattern for the seasonality of
      days open (DO) by state and region within the United States and to present
      statistics on regional trends for DO. Data included 8,676,915 records on DO for
      Holsteins from 1997 to 2002 covering all regions of the United States. Fixed
      effects in the model included herd, parity, milk-class, state x month of calving
      (MOC), year of calving x MOC, and parity x MOC. Least squares means of DO were
      highest for calvings in March and lowest for calvings in September. The highest
      mean DO of 155 d was recorded in the Southeast, while the mean DO for the
      Midwest, Northeast, Northwest, and Southwest were 142, 141, 140, and 137 d,
      respectively. Variation in monthly averages of DO was highest in Southeast with a
      range of 51 d, and less than 25 d in all the other regions. Seasonality of
      calving was defined as the ratio of the fewest to the most calvings in months.
      The SOC was > or = 60% in Southeast and < or = 23% in the other regions. Selected
      states: Texas, Oklahoma, and Arizona in the Southwest and Missouri, Kansas, and
      Kentucky in the Midwest showed patterns of variation in monthly averages and
      seasonality of calving similar to those of Southeast. Distributions of DO were
      bimodal for some months of calving due to postponed breeding during the hot
      season or depressed fertility as a result of thermal stress; the second mode at >
      200 d was highest in the Southeast but also could be observed in Texas,
      Wisconsin, and California. High level of heat stress for DO exists in the
      Southeast and in selected states of the Midwest and the Southwest; these regions
      contribute less than 10% of national records. A methodology for analyzing DO
      especially under heat stress needs to consider effects of intentionally delayed
      breeding--by using a model that accounts for bimodality, for example.

PMID- 14672203
TI  - Short communication: Simultaneous identification of five kappa-casein (CSN3)
      alleles in domestic goat by polymerase chain reaction-single strand conformation
      polymorphism.
AB  - Until now, a total of nine polymorphic sites corresponding to six different
      alleles have been described at the kappa-casein (CSN3) locus in the domestic goat
      (Capra hircus). A protocol for the rapid and simultaneous genotyping of five goat
      CSN3 alleles by using polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) technique was developed. Moreover, the developed test was
      validated by screening the CSN3 variability in four Italian breeds, Garganica,
      Jonica, Maltese, and Camosciata. Seven different patterns were readily
      identifiable. These corresponded to five known alleles and two newly identified
      variants. The G/A substitution at nucleotide position 471, which is not
      identifiable at the protein level but was found to be very frequent in the typed
      breeds, is easily detectable by the protocol developed. The PCR-SSCP analysis is
      a powerful tool for the genetic study of CSN3 variability in domestic goats,
      allowing both the simultaneous identification of different alleles, and the
      detection of new variants.

PMID- 14672204
TI  - Genetic relationship between body condition score, dairy character, mastitis, and
      diseases other than mastitis in first-parity Danish Holstein cows.
AB  - The aim of this study was to explore the possibilities of using body condition
      score (BCS) or dairy character (DC) as indicators of mastitis and diseases other
      than mastitis in first-parity Danish Holsteins. The dataset included 28,948
      observations on conformation scores and 365,136 disease observations. The
      analysis was performed using a multitrait linear sire model. Heritability
      estimates for BCS and DC were moderate (0.25 and 0.22), and heritability
      estimates for mastitis and diseases other than mastitis were low (0.038 and
      0.022). Between BCS and diseases other than mastitis, the genetic correlation was
      -0.22, whereas the genetic correlation was -0.16 between BCS and mastitis. The
      genetic correlation between DC and diseases other than mastitis was 0.43, and
      between DC and mastitis it was 0.27. The genetic correlation between BCS and DC
      was -0.61. Residual correlations were close to 0, except between BCS and DC (
      0.37). Including DC as an indicator of diseases other than mastitis will increase
      the accuracy of the predicted breeding value for diseases, especially when the
      progeny group is small. Using BCS as an additional indicator of diseases did not
      increase the accuracy. Breeding for less DC will increase resistance to diseases.

PMID- 14672205
TI  - Genotype x environment interaction for milk production of daughters of Australian
      dairy sires from test-day records.
AB  - In Australia, dairy farming is carried out in environments that vary in many
      ways, including level of feeding and climate variables such as temperature and
      humidity. The aim of this study was to assess the magnitude of genotype x
      environment interactions (GxE) on milk production traits (milk yield, protein
      yield, and fat yield) for a range of environmental descriptors. The environment
      on individual test days was described by herd size (HS), average herd protein
      yield (AHTDP), herd test-day coefficient of variation for protein yield (HTDCV),
      and temperature humidity index (THI). A sire random regression model was used to
      model the response of a sire's daughters to variation in the environment and to
      calculate the genetic correlation between the same traits measured in two widely
      different environments. Using test-day records, rather than average lactation
      yields, allowed exploitation of within-cow variation as well as between-cow
      variation at different levels of AHTDP, and led to more accurate estimates of
      sire breeding values for "response to environment." The greatest GxE observed was
      due to variation in AHTDP, with a genetic correlation of 0.78 between protein
      yield when AHTDP = 0.54 kg and protein yield when AHTDP = 1.1 kg (the 5th and
      95th percentile of the distribution of AHTDP). The GxE was also observed for THI,
      with a genetic correlation of 0.90 between protein yield at the 5th and 95th
      percentile of THI. The use of response to environment estimated breeding values
      to improve the accuracy of international sire evaluations is discussed.

PMID- 14672206
TI  - Birth weight as a predictor of calving ease and perinatal mortality in Holstein
      cattle.
AB  - The objective of this research was to determine the effect of birth weight on
      perinatal mortality (PM) (alive or dead at 48 h of age) and dystocia (unassisted
      or assisted). Data were 4528 records of births between 1968 and 1999 from the
      Iowa State University research dairy farm in Ankeny. The incidence of PM was
      7.1%; dystocia was 23.7%. A logistic regression model was used to predict both PM
      and dystocia. The PM model included effects of year of birth, season (summer or
      winter), dystocia, parity (first or later), birth weight (kg), ratio of calfs
      birth weight to dam's weight (%), and gestation length (d). Odds of PM increased
      by 2.1%/yr. Calves born in the winter have a 36% higher risk of PM than calves
      born in the summer. Difficult births tend to result in PM 2.7 times more often
      than unassisted births. First-parity cows have a 2.4 times higher risk of PM than
      cows in later parities. Probabilities of PM for birth weights of 29, 35, 40, 46,
      and 52 kg were 2.1, 2.5, 3.4, 5.1, and 9.6%, respectively, when other factors
      were set at their average value. Similarly, ratios of calf to cow weight of 4.5,
      5.7, 6.9, 8.1, and 9.3% yield probabilities of PM at 8.2, 4.2, 3.1, 3.5, and
      5.7%, respectively. Finally, gestation lengths of 268, 273, 279, 284, and 290 d
      yield probabilities of PM of 5.5, 3.9, 3.1, 3.1, and 3.6%, respectively. The
      dystocia model included effects of year of birth, season, sex of calf, PM,
      parity, birth weight, and pelvic area (externally measured). Odds for dystocia
      decreased by 4.7%/yr. Calves born in the winter have a 15% higher risk of
      dystocia than calves born in the summer. Odds of male calves needing assistance
      were 25% greater than female calves. If a calf died in the first 48 h, then it is
      2.7 times more likely that the calf needed assistance. First-parity cows have a
      4.7 times higher risk of dystocia than cows in later parities. Odds of dystocia
      increase by 13%/kg increase in birth weight. An 11% decrease in odds for dystocia
      is associated with a one square decimeter (dm2) increase in pelvic area.

PMID- 14672207
TI  - Estimation of environmental sensitivity of genetic merit for milk production
      traits using a random regression model.
AB  - The objective of this study was to estimate effects of environmental sensitivity
      of milk production traits for several environmental parameters and to investigate
      the impact of combining traits with different environmental sensitivity in an
      economic index. Variance components and breeding values were estimated for milk,
      fat, and protein yield, and fat and protein percentage by applying a random
      regression on values of an environmental parameter for each sire. Fourteen
      environmental parameters were defined and fitted to data consisting of 151,696
      heifers in 6780 herds in The Netherlands with first-lactation records for milk
      production, somatic cell count, body condition score, and number of
      inseminations. Milk, fat, and protein yield showed environmental sensitivity in
      combination with 12 environmental parameters. Herd-year averages of protein, body
      condition score, age at calving, calving interval, and peak date of calving
      explained most genotype by environment interaction, mainly resulting from scaling
      effects. Almost all genetic correlations across environments were 0.99 or higher.
      Although heterogeneity of genetic variances was considerable, heterogeneity of
      heritabilities was limited. Scaling had a large effect on the weights of the
      economic index, but environmental sensitivities of milk, fat, and protein yields
      were approximately of equal magnitude. Consequently, very little reranking
      occurred based on the economic index.

PMID- 14672208
TI  - Within-herd effects of age at test day and lactation stage on test-day yields.
AB  - Variance ratios were estimated for random within-herd effects of age at test day
      and lactation stage, on test-day yield and somatic cell score to determine
      whether including these effects would improve the accuracy of estimation. Test
      day data starting with 1990 calvings for the entire US Jersey population and
      Holsteins from California, Pennsylvania, Wisconsin, and Texas were analyzed. Test
      day yields were adjusted for across-herd effects using solutions from a regional
      analysis. Estimates of the relative variance (fraction of total variance) due to
      within-herd age effects were small, indicating that regional adjustments for age
      were adequate. The relative variances for within-herd lactation stage were large
      enough to indicate that accuracy of genetic evaluations could be improved by
      including herd stage effects in the model for milk, fat, and protein, but not for
      somatic cell score. Because the within-herd lactation stage effect is assumed to
      be random, the effect is regressed toward the regional effects for small herds,
      but in large herds, lactation curves become herd specific. Model comparisons
      demonstrated the greater explanatory power of the model with a within-herd-stage
      effect as prediction error standard deviations were greater for the model without
      this effect. The benefit of the within-herd-stage effects was confirmed in a
      random regression model by comparing variance components from models with and
      without random within-herd regressions and through log-likelihood ratio tests.

PMID- 14672209
TI  - Functionality of extrusion--texturized whey proteins.
AB  - Whey, a byproduct of the cheesemaking process, is concentrated by processors to
      make whey protein concentrates (WPC) and isolates (WPI). Only 50% of whey
      proteins are used in foods. In order to increase their usage, texturizing WPC,
      WPI, and whey albumin is proposed to create ingredients with new functionality.
      Extrusion processing texturizes globular proteins by shearing and stretching them
      into aligned or entangled fibrous bundles. In this study, WPC, WPI, and whey
      albumin were extruded in a twin screw extruder at approximately 38% moisture
      content (15.2 ml/min, feed rate 25 g/min) and, at different extrusion cook
      temperatures, at the same temperature for the last four zones before the die (35,
      50, 75, and 100 degrees C, respectively). Protein solubility, gelation, foaming,
      and digestibility were determined in extrudates. Degree of extrusion-induced
      insolubility (denaturation) or texturization, determined by lack of solubility at
      pH 7 for WPI, increased from 30 to 60, 85, and 95% for the four temperature
      conditions 35, 50, 75, and 100 degrees C, respectively. Gel strength of extruded
      isolates increased initially 115% (35 degrees C) and 145% (50 degrees C), but gel
      strength was lost at 75 and 100 degrees C. Denaturation at these melt
      temperatures had minimal effect on foaming and digestibility. Varying extrusion
      cook temperature allowed a new controlled rate of denaturation, indicating that a
      texturized ingredient with a predetermined functionality based on degree of
      denaturation can be created.

PMID- 14672210
TI  - Efficacy of two iodine teat dips during experimental challenge with
      Staphylococcus aureus and Streptococcus agalactiae.
AB  - An experimental challenge trial was performed against Staphylococcus aureus and
      Streptococcus agalactiae following the procedures recommended by the National
      Mastitis Council. The efficacy of two teat dips, product 1 (Bovadine with I-Tech
      II) and product 2 (Bovadine with I-Tech, used as a positive control), was
      determined. Both teat dips contain 1% iodine and 10% glycerin. Product 1
      established an 89.7% reduction in infections against Staph. aureus and 73.1%
      reduction in infections against Strep. agalactiae. Product 2 demonstrated an
      86.2% reduction in infections against Staph. aureus and 78.4% reduction in
      infections against Strep. agalactiae. Teat skin and teat ends were evaluated
      before and after the trial. No significant change in teat condition was observed
      for either product.

PMID- 14672211
TI  - Phosphorus feeding levels and critical control points on dairy farms.
AB  - A viable and cost-effective approach to managing P on dairy farms is to minimize
      excess P in diets, which in turn leads to less excretion of P in manure without
      impairing animal performance. A questionnaire survey was conducted, coupled with
      on-site feed and fecal sample collection and analysis on dairy farms in New York,
      Pennsylvania, Delaware, Maryland, and Virginia. The purpose was to assess dietary
      P levels and to identify critical control points pertaining to P feeding
      management. Survey responses, 612 out of 2500 randomly selected farms, revealed a
      wide range of dietary P concentrations for lactating cows, from 3.6 to 7.0 g/kg
      of feed DM. The mean was 4.4 g/kg, which was 34% above the level recommended by
      the NRC for 27.9 kg milk/d, the mean milk yield in the survey. Higher P
      concentrations in diets were not associated with higher milk yields (n = 98, R2 =
      0.057 for the survey farms; n = 92, R2 = 0.043 for farms selected for on-site
      sampling). However, higher dietary P led to higher P excretion in feces (n = 75,
      R2 = 0.429), with much of the increased fecal P being water soluble. Phosphorus
      concentrations in diet samples matched closely with P concentrations in
      formulated rations, with 67% of the feed samples deviating <10% from the
      formulations. On 84% of the survey farms, ration formulation was provided by
      professionals rather than producers themselves. Most producers were feeding more
      P than cows needed because it was recommended in the rations by these
      consultants. In conclusion, P fed to lactating cows averaged 34% above NRC
      recommendations; to reduce excess dietary P, ration formulation is the critical
      control point.

PMID- 14672213
TI  - Persistence of Escherichia coli O157:H7 on lettuce plants following spray
      irrigation with contaminated water.
AB  - Irrigation water collected at farms growing crops for human consumption was
      artificially contaminated with E. coli O157:H7 and used to irrigate lettuce
      plants. Plants in a growth chamber were spray irrigated either once or
      intermittently with water contaminated with 10(2) or 10(4) CFU of E. coli O157:H7
      per ml and were then sampled over a 30-day period. Only plants exposed to 10(2)
      CFU/ml on day 1 did not harbor the pathogen at the end of the sampling period.
      All other treatments resulted in contaminated plants at harvest. Plants irrigated
      with 10(4) CFU/ml contained high levels (up to 5 log CFU/g) of the pathogen at
      harvest. The results obtained in this study underscore the assertion that spray
      irrigation (the application of water directly to plant leaves) is linked to the
      contamination of crops and suggest that repeated exposure increases the E. coli
      O157:H7 level on the plant.

PMID- 14672212
TI  - Efficiency of converting nutrient dry matter to milk in Holstein herds.
AB  - Production of milk from feed dry matter intakes (DMI), called dairy or feed
      efficiency, is not commonly measured in dairy herds as is feed conversion to
      weight gain in swine, beef, and poultry; however, it has relevance to conversion
      of purchased input to salable product and proportion of dietary nutrients
      excreted. The purpose of this study was to identify some readily measured factors
      that affect dairy efficiency. Data were collected from 13 dairy herds visited 34
      times over a 14-mo period. Variables measured included cool or warm season (high
      ambient temperature <21 degrees C or >21 degrees C, respectively), days in milk,
      DMI, milk yield, milk fat percent, herd size, dietary concentrations (DM basis)
      and kilograms of crude protein (CP), acid detergent fiber (ADF), neutral
      detergent fiber (NDF), and forage. Season, days in milk, CP % and forage % of
      diet DM, and kilograms of dietary CP affected dairy efficiency. When evaluated
      using a model containing the significant variables, dairy efficiency was lower in
      the warm season (1.31) than in the cool season (1.40). In terms of simple
      correlations, dairy efficiency was negatively correlated with days in milk (r = 
      0.529), DMI (r = -0.316), forage % (r = -0.430), NDF % (r = -0.308), and
      kilograms of forage (r = -0.516), NDF (r = -0.434), and ADF (r = -0.313), in the
      diet, respectively. Dairy efficiency was positively correlated with milk yield (r
      = 0.707). The same relative patterns of significance and correlation were noted
      for dairy efficiency calculated with 3.5% fat-corrected milk yield. Diets fed by
      the herds fell within such a small range of variation (mean +/- standard
      deviation) for CP % (16.3 +/- 0.696), NDF % (33.2 +/- 2.68), and forage % (46.9
      +/- 5.56) that these would not be expected to be useful to evaluate the effect of
      excessive underfeeding or overfeeding of these dietary components. The negative
      relationships of dairy efficiency with increasing dietary fiber and forage may
      reflect the effect of decreased diet digestibility. The results of this study
      suggest that managing herd breeding programs to reduce average days in milk and
      providing a cooler environment for the cows may help to maximize dairy
      efficiency. The mechanisms for the effects of the dietary variables on dairy
      efficiency need to be understood and evaluated over a broader range of diets and
      conditions before more firm conclusions regarding their impact can be drawn.

PMID- 14672214
TI  - Survival and growth of Listeria monocytogenes and enterohemorrhagic Escherichia
      coli O157:H7 in minimally processed artichokes.
AB  - The ability of Listeria monocytogenes and Escherichia coli O157:H7 inoculated by
      immersion (at 4.6 and 5.5 log CFU/ g, respectively) to survive on artichokes
      during various stages of preparation was determined. Peeling, cutting, and
      disinfecting operations (immersion in 50 ppm of a free chlorine solution at 4
      degrees C for 5 min) reduced populations of L. monocytogenes and E. coli O157:H7
      by only 1.6 and 0.8 log units, respectively. An organic acid rinse (0.02% citric
      acid and 0.2% ascorbic acid) was more effective than a tap water rinse in
      removing these pathogens. Given the possibility of both pathogens being present
      on artichokes at the packaging stage, their behavior during the storage of
      minimally processed artichokes was investigated. For this purpose, batches of
      artichokes inoculated with L. monocytogenes or E. coli O157:H7 (at 5.5 and 5.2
      log CFU/g, respectively) were packaged in P-Plus film bags and stored at 4
      degrees C for 16 days. During this period, the equilibrium atmosphere composition
      and natural background microflora (mesophiles, psychrotrophs, anaerobes, and
      fecal coliforms) were also analyzed. For the two studied pathogens, the inoculum
      did not have any effect on the final atmospheric composition (10% O2, 13% CO2) or
      on the survival of the natural background microflora of the artichokes. L.
      monocytogenes was able to survive during the entire storage period in the
      inoculated batches, while the E. coli O157:H7 level increased by 1.5 log units in
      the inoculated batch during the storage period. The modified atmosphere was
      unable to control the behavior of either pathogen.

PMID- 14672215
TI  - Efficacy of detergents in removing Salmonella and Shigella spp. from the surface
      of fresh produce.
AB  - Fresh produce has been implicated in several foodborne disease outbreaks. Produce
      surfaces can be primary sites of contamination during production and handling.
      One approach to reduce contamination is to treat fresh produce with rinsing
      agents. In this study, different detergent agents were used at 22 and 40 degrees
      C to determine their efficacy in removing Salmonella and Shigella spp. from the
      surfaces of strawberries, tomatoes, and green-leaf lettuce. Produce was
      inoculated at 22 degrees C with a cocktail of nalidixic acid-resistant organisms
      (6 to 6.5 log CFU/ml). After air drying for 1 h, samples were rinsed with either
      0.1% Tween 80, 0.1% sodium lauryl sulfate (SLS), or water (control) at 22 or 40
      degrees C. Rinse solutions were spiral plated onto tryptic soy agar supplemented
      with 50 mg of nalidixic acid per liter. In trials involving strawberries and
      lettuce, Salmonella and Shigella were removed at levels of 4 and 3 log CFU/ml,
      respectively, except from Salmonella-inoculated strawberries rinsed with SLS, for
      which minimal removal rates were 1.5 log CFU/ml at 22 degrees C and < 1 log
      CFU/ml at 40 degrees C. When whole strawberries were analyzed after rinsing with
      SLS, few organisms were recovered. This result suggests that SLS may have a
      lethal or sublethal effect on Salmonella, especially when a 40 degrees C solution
      is used. Salmonella and Shigella removal rates for tomatoes were 1 and 1.5 log
      CFU/ml lower, respectively, than those for strawberries or lettuce. Overall,
      detergents were no more effective in removing organisms from produce than water
      was. The detergents examined would not constitute effective overall produce rinse
      treatments.

PMID- 14672216
TI  - Combined effects of temperature, water activity, and pH on Alicyclobacillus
      acidoterrestris spores.
AB  - A response surface model was developed to describe the effects of temperature (35
      to 55 degrees C), pH (3.5 to 5.5), and water activity (a(w), 0.960 to 0.992) on
      germination of Alicyclobacillus acidoterrestris spores. Germination and growth or
      viability loss depended, to varying extents, on the interactions among the
      independent variables and the complexity of the medium. In particular, maximum
      growth was achieved at temperatures between 35 and 42 degrees C and at pH values
      from 3.5 to 4.5. The model was validated against data not used in its
      development. Bias factors of 0.999 and 0.817 for 2- and 7-day models,
      respectively, were obtained, indicating that the models were "fail safe." Results
      indicated that the model provided reliable predictions of growth of A.
      acidoterrestris spores.

PMID- 14672217
TI  - Direct microscopic observation and viability determination of Campylobacter
      jejuni on chicken skin.
AB  - A method was developed to determine the survival of Campylobacter jejuni at
      specific sites on chicken skin, and this method was used to observe the survival
      of C. jejuni at various locations on the skin during storage. This method uses
      confocal scanning laser microscopy to visualize C. jejuni transformed with
      P(c)gfp plasmid (GFP-Campylobacter) and stained with 5-cyano-2,3-ditolyl
      tetrazolium chloride (CTC). The green fluorescence of dead C. jejuni cells and
      the red fluorescent CTC-formazan in viable Campylobacter cells were clearly
      visible on chicken skin. The GFP-Campylobacter remaining on the chicken skin
      surface after rinsing was mostly located in crevices, entrapped inside feather
      follicles with water, and entrapped in the surface water layer. Most viable cells
      were entrapped with water in the skin crevices and feather follicles. These sites
      provide a suitable microenvironment for GFP-Campylobacter to survive. The
      population of C. jejuni on chicken skin decreased by 1 log unit during storage at
      25 degrees C for 24 h. C. jejuni located in sites 20 to 30 microm beneath the
      chicken skin surface maintained viability during incubation at 25 degrees C. C.
      jejuni on chicken skin stored at 4 degrees C maintained constant numbers during a
      72-h incubation with no significant changes in population feather follicles or
      crevices. Live and dead cells were initially retained with water on the skin and
      penetrated into the skin follicles and channels during storage. Microscopic
      observations of GFP-producing cells allowed the identification of survival niches
      for C. jejuni present on chicken skin.

PMID- 14672218
TI  - Transfer of Salmonella and Campylobacter from stainless steel to romaine lettuce.
AB  - The degree of transfer of Campylobacter jejuni and Salmonella enterica serovar
      Typhimurium was evaluated from a stainless steel contact surface to a ready-to
      eat food (lettuce). Stainless steel coupons (25 cm2) were inoculated with a 20
      microl drop of either C. jejuni or Salmonella Typhimurium to provide an inoculum
      level of approximately 10(6) CFU/28 mm2. Wet and dry lettuce (Lactuca sativa var.
      longifolia) pieces (9 cm2) were placed onto the inoculated stainless steel
      surface for 10 s after the designated inoculum drying time (0 to 80 min for C.
      jejuni; 0 to 120 min for Salmonella Typhimurium), which was followed by the
      recovery and enumeration of transferred pathogens (lettuce) and residual surface
      pathogens (stainless steel coupons). For transfers of Salmonella Typhimurium to
      dry lettuce, there was an increase from 36 to 66% in the percent transfer of the
      initial inoculum load during the first 60 min of sampling and then a precipitous
      drop from 66 to 6% in percent transfer. The transfer of Salmonella Typhimurium to
      wet lettuce ranged from 23 to 31%, with no statistically significant difference
      between recoveries over the entire 120-min sampling period. For C. jejuni, the
      mean percent transfer ranged from 16 to 38% for dry lettuce and from 15 to 27%
      for wet lettuce during the 80-min sampling period. The results of this study
      indicate that relatively high numbers of bacteria may be transferred to a food
      even 1 to 2 h after surface contamination. These findings can be used to support
      future projects aimed at estimating the degree of risk associated with poor
      handling practices of ready-to-eat foods.

PMID- 14672219
TI  - Isolation and characterization of Escherichia coli recovered from Maryland apple
      cider and the cider production environment.
AB  - Contaminated apple cider has been implicated in several Escherichia coli O157:H7
      outbreaks. In an attempt to investigate sources and modes of entry of E. coli
      into apple cider, samples of fresh apple, pomace, and cider and equipment and
      mill floor swabs were analyzed for standard plate counts (SPC), total coliforms
      (TC), fecal coliforms (FC), and E. coli. E. coli was isolated from 14 (33%) of 42
      samples of bottled fresh cider, from food equipment in 6 (67%) of 9 mills, and
      from apples, pomace, or cider in 7 (78%) of 9 mills. Seventy-five E. coli
      isolates were further characterized for Shiga toxin-producing E. coli (STEC)
      associated virulence factors, antimicrobial susceptibility, and pulsed-field gel
      electrophoresis (PFGE) type. No E. coli O157:H7 or other STEC was identified.
      Serotyping and PFGE revealed 64 distinct profiles, suggesting that recovered E.
      coli arose from multiple independent sources. However, on one occasion, E. coli
      isolated from the source apple sample was closely related to the E. coli
      identified in the finished cider sample. E. coli isolates were further tested for
      antimicrobial susceptibility to 17 antimicrobial agents of human and veterinary
      importance. Fourteen (19%) of the 75 isolates were resistant to at least one of
      the antimicrobial agents tested, and 9 (12%) were resistant to at least two of
      these agents. Of the resistant isolates recovered, 64% were resistant to
      tetracycline and 57% were resistant to streptomycin. Overall, the level of E.
      coli contamination in source apple samples did not differ significantly from
      those in samples of pomace, cider at the press, and cider entering the bottling
      tank; therefore, source apples cannot be dismissed as a potential contributor of
      E. coli to the cider-making process.

PMID- 14672220
TI  - Inactivation of Salmonella during drying and storage of apple slices treated with
      acidic or sodium metabisulfite solutions.
AB  - This study was undertaken to determine whether pretreating inoculated Gala apple
      slices with metabisulfite or acidic solutions enhanced the inactivation of
      Salmonella during dehydration and storage. Apple slices inoculated with a five
      strain mixture of Salmonella (7.6 log CFU/g) were pretreated, dried for 6 h at 60
      degrees C, and stored aerobically at 25 degrees C for 28 days. Predrying
      treatments included (i) no treatment, (ii) 10 min of immersion in sterile water,
      (iii) 10 min of immersion in a 4.18% sodium metabisulfite solution, (iv) 10 min
      of immersion in a 3.40% ascorbic acid solution, and (v) 10 min of immersion in a
      0.21% citric acid solution. Samples were plated on tryptic soy agar with 0.1%
      pyruvate (TSAP), brilliant green sulfa (BGS) agar, and xylose lysine tergitol 4
      (XLT4) agar for the enumeration of bacteria. Populations were not significantly
      (P > 0.05) reduced by immersion in water but were reduced by 0.7 to 1.1 log CFU/g
      by immersion in acidic solutions. Immersion in the sodium metabisulfite solution
      reduced populations by 0.4, 1.3, and 5.4 log CFU/g on TSAP, BGS agar, and XLT4
      agar, respectively. After 6 h of dehydration at 60 degrees C, populations on
      untreated and water-treated slices were reduced by 2.7 to 2.8, 2.7 to 2.9, and
      4.0 to 4.2 log CFU/g as determined with TSAP, BGS agar, and XLT4 agar,
      respectively. In contrast, populations on slices treated with sodium
      metabisulfite, ascorbic acid, and citric acid were reduced after 6 h of
      dehydration by 4.3, 5.2, and 3.8 log CFU/g, respectively, as determined with
      TSAP; by 4.7, 5.5, and 3.9 log CFU/g, respectively, as determined with BGS agar;
      and by 5.5, 5.7, and 5.6 log CFU/g, respectively, as determined with XLT4 agar.
      Bacteria were still detectable by direct plating after 28 days except on slices
      treated with ascorbic acid. Immersion in metabisulfite or acidic solutions prior
      to dehydration should enhance the inactivation of Salmonella during the
      dehydration and storage of Gala apple slices.

PMID- 14672221
TI  - Nitrite-induced injury of Listeria monocytogenes and the effect of selective
      versus nonselective recovery procedures on its isolation from frankfurters.
AB  - Sodium nitrite (NaNO2) is used as a curing agent in frankfurters. Although
      previous studies have documented the bacteriostatic abilities of NaNO2 toward
      Listeria monocytogenes, few if any studies have been conducted that consider the
      possibility of sublethal injury to L. monocytogenes by exposure to NaNO2. The
      goals of this study were to determine whether NaNO2 has the ability to injure L.
      monocytogenes, to determine whether nitrite injury is reversible, and to compare
      the recovery of L. monocytogenes from frankfurters containing nitrite with
      Listeria repair broth (LRB) and University of Vermont modified Listeria
      enrichment broth (UVM). NaNO2, when used at concentrations of 100 and 200 ppm,
      was found to injure L. monocytogenes. The injury was completely reversible, or
      growth of uninjured Listeria occurred in LRB when injury was between 98.5 and
      98.7%. However, total recovery was not observed in LRB when injury exceeded 99%.
      UVM was unable to reverse the effects of nitrite-injured L. monocytogenes. With
      respect to time, inoculum, and meat type, LRB was found to be consistently
      superior to UVM at recovering L. monocytogenes from frankfurters. Nitrite injury
      might be a factor influencing detection and recovery of L. monocytogenes from
      frankfurters.

PMID- 14672222
TI  - Influence of extended acid stressing in fresh beef decontamination runoff fluids
      on sanitizer resistance of acid-adapted Escherichia coli O157:H7 in biofilms.
AB  - This study evaluated resistance to sanitizing solutions of Escherichia coli
      O157:H7 cells forming biofilms on stainless steel coupons exposed to inoculated
      meat decontamination runoff fluids (washings). A previously acid-adapted culture
      of a rifampicin-resistant derivative of E. coli O157:H7 strain ATCC 43895 was
      inoculated in unsterilized or sterilized combined hot-water (85 degrees C) and
      cold-water (10 degrees C) (50/50 [vol/vol]) composite water (W) washings (pH 6.29
      to 6.47) and in W washings mixed with 2% acetic acid (pH 4.60 to 4.71) or in 2%
      lactic acid W washings (pH 4.33 to 4.48) at a ratio of 1/99 (vol/vol). Stainless
      steel coupons (2 by 5 by 0.08 cm) were submerged in the inoculated washings and
      stored for up to 14 days at 15 degrees C. Survival of E. coli O157:H7 was
      determined after exposure (0 to 60 s for cells in suspension and 0 to 300 s for
      attached cells) to two commercial sanitizers (150 ppm peroxyacetic acid and 200
      ppm quaternary ammonium compound) at 2, 7, and 14 days. E. coli O157:H7 attached
      more rapidly to coupons submerged in washings containing the natural flora than
      to those without. The attached cells were more resistant to the effects of the
      sanitizers than were the cells in suspension, and survival was highest in the
      presence of the natural flora. Attached cells in the presence of dilute acid
      washings were more sensitive to subsequent sanitizer treatments than were cells
      generated in the presence of W washings. Under the conditions of this study,
      cells of E. coli O157:H7 in W washings were more sensitive to acidic
      (peroxyacetic acid) than to alkaline (quaternary ammonium) sanitizers during
      storage. These results suggest that meat processing plants that apply no
      decontamination or that use only water washings of meat should consider using
      acidic sanitizers to enhance biofilm removal. Plants that apply both water and
      acidic washings may create a sublethal acid-stressing environment in the runoff
      fluids, sensitizing biofilm cells to subsequent sanitizing treatments.

PMID- 14672223
TI  - A model study of Escherichia coli O157:H7 survival in fermented dry sausages-
      influence of inoculum preparation, inoculation procedure, and selected process
      parameters.
AB  - The influence of inoculum preparation, inoculation level, and inoculation
      procedure on Escherichia coli O157:H7 inactivation during the manufacture of
      fermented sausage was evaluated in a model study. Prior growth in glucose
      enriched tryptone soya broth, which provided exposure to mildly acidic conditions
      (pH 4.8), had no effect on the later survival of E. coli O157: H7 strains 5-1 and
      ATCC 43894 under extremely acidic conditions (pH 2), but the same strains became
      sensitive to acidity after 7 days of incubation on the surface of refrigerated
      beef (as per the normal contamination route from slaughter to further
      processing). In subsequent sausage production trials, the extent of destruction
      observed for E. coli O157:H7 strains F-90, 5-1, and ATCC 43894 inoculated
      directly into the meat batter was unchanged when the inoculation level was
      decreased from 7.3 to 4.7 log CFU/g, but the level of inactivation was ca. 1 log
      higher when the surfaces of beef cuts, rather than the batter, were inoculated 7
      days prior to processing. Regardless of processing conditions (fermentation to a
      pH of < or = 5.0 at 24 or 37 degrees C, drying at 14 degrees C to a water
      activity [a(w)] value of 0.91 or 0.79), strains F-90, 5-1, and ATCC 43894 showed
      similar survival capacities during the manufacture of sausage. A approximately 2
      log reduction in pathogen numbers was generally obtained after samples were dried
      to an a(w) of 0.91, irrespective of fermentation temperature. The addition of a 5
      day predrying holding stage at the fermentation temperature significantly (P <
      0.05) increased pathogen inactivation when fermentation was carried out at 37
      degrees C (but not when it was carried out at 24 degrees C). However, significant
      pathogen reductions (4 to 5 log CFU/g) were achieved only for extensively dried
      products (a(w) = 0.79).

PMID- 14672224
TI  - Sensitivity of Vibrio species in phosphate-buffered saline and in oysters to high
      pressure processing.
AB  - Multiple strains of Vibrio vulnificus, Vibrio parahaemolyticus, and Vibrio
      cholerae non-O1 were tested in phosphate-buffered saline for their sensitivity to
      high-pressure processing (HPP). Variability in sensitivity among strains was
      observed for all species; this variability decreased at higher pressures. V.
      vulnificus was the species that was most sensitive to treatment at 200 MPa
      (decimal reduction time [D] = 26 s), and V. cholerae was the species that was
      most resistant to treatment at 200 MPa (D = 149 s). The O3:K6 serotype of V.
      parahaemolyticus was more resistant to pressure than other serotypes of V.
      parahaemolyticus were. The results of studies involving V. vulnificus naturally
      occurring in oysters revealed that a pressure treatment of 250 MPa for 120 s
      achieved a > 5-log reduction in the levels of this bacterium. V. parahaemolyticus
      serotype O3:K6 in oysters required a pressure of 300 MPa for 180 s for a
      comparable 5-log reduction. When properly applied, HPP can be effective in
      improving the safety of shellfish with respect to Vibrio spp.

PMID- 14672225
TI  - Relationship between the effects of stress induced by human bile juice and acid
      treatment in Vibrio cholerae.
AB  - The effects of low pH and human bile juice on Vibrio cholerae were investigated.
      A mild stress condition (exposure to acid shock at pH 5.5 or exposure to 3 mg of
      bile per ml for 20 min) slightly decreased (by < or = 1 log unit) V. cholerae
      cell viability. However, these treatments induced tolerance to subsequent
      exposures to more severe stress. In the O1 strain, four proteins were induced in
      response to acid shock (ca. 101, 94, 90, and 75 kDa), whereas only one protein
      (ca. 101 kDa) was induced in response to acid shock in the O139 strain. Eleven
      proteins were induced in response to bile shock in the O1 strain (ca. 106, 103,
      101, 96, 88, 86, 84, 80, 66, 56, and 46 kDa), whereas only one protein was
      induced in response to bile shock in the O139 strain (ca. 88 kDa). V. cholerae O1
      and O139 cells that had been preexposed to mild acid shock were twofold more
      resistant to pH 4.5 (with times required to inactivate 90% of the cell population
      [D-values] of 59 to 73 min) than were control cells (with D-values of 24 to 27
      min). Likewise, cells that were preexposed to mild bile shock (3 mg/ml) were
      almost twofold more tolerant of severe bile shock (30 mg/ml; D-values, 68 to 87
      min) than were control cells (with D-values of 37 to 43 min). These protective
      effects persisted for at least 1 h after the initial shock but were abolished
      when chloramphenicol was added to the culture during the shock. Cells preexposed
      to acid shock exhibited cross-protection against subsequent bile shock. However,
      cells preexposed to bile shock exhibited no changes in acid tolerance. Bile shock
      induced a modest reduction (0 to 20%) in enterotoxin production in V. cholerae,
      whereas acid shock had no effect on enterotoxin levels. Adaptation to acid and
      bile juice and protection against bile shock in response to preexposure to acid
      shock would be predicted to enhance the survival of V. cholerae in hosts and in
      foods. Thus, these adaptations may play an important role in the development of
      cholera disease.

PMID- 14672226
TI  - Tolerance of Salmonella Enteritidis and Staphylococcus aureus to surface cleaning
      and household bleach.
AB  - Effective cleaning and sanitizing of food preparation sites is important because
      pathogens are readily spread to food contact surfaces after preparation of
      contaminated raw products. Tolerance of Salmonella Enteritidis and Staphylococcus
      aureus to surface cleaning by wiping with regular, microfiber, and antibacterial
      treated cloths was investigated. Wiping with cleaning cloths resulted in a
      considerable reduction of microorganisms from surfaces, despite the greater
      difficulty in removing S. aureus than Salmonella Enteritidis. Depending on the
      cloth type, S. aureus were reduced on surfaces from initial numbers of
      approximately 10(5) CFU/100 cm2 to numbers from less than 4 CFU/100 cm2 (below
      the detection limit) to 100 CFU/100 cm2. Directly after the cloths were used to
      clean the contaminated surfaces, they contained high numbers of bacteria (10(4)
      to 10(5) CFU/100 cm2), except for the disposable antibacterial-treated cloths, in
      which no bacteria could be detected. The tolerance of these pathogens to sodium
      hypochlorite was studied in the suspension test and in cloths. S. aureus showed a
      better tolerance for sodium hypochlorite than Salmonella Enteritidis.
      Inactivation of microorganisms in cloths required a higher concentration of
      sodium hypochlorite than was needed in the suspension test. Repeated exposure to
      sodium hypochlorite, however, resulted in an increase in susceptibility to this
      compound. This study provides essential information about the transfer of
      bacteria when wiping surfaces and highlights the need for a hygiene procedure
      with cleaning cloths that sufficiently avoids cross-contamination in the
      household environment.

PMID- 14672227
TI  - A comparison of hand washing techniques to remove Escherichia coli and
      caliciviruses under natural or artificial fingernails.
AB  - Compared with other parts of the hand, the area beneath fingernails harbors the
      most microorganisms and is most difficult to clean. Artificial fingernails, which
      are usually long and polished, reportedly harbor higher microbial populations
      than natural nails. Hence, the efficacy of different hand washing methods for
      removing microbes from natural and artificial fingernails was evaluated. Strains
      of nonpathogenic Escherichia coli JM109 and feline calicivirus (FCV) strain F9
      were used as bacterial and viral indicators, respectively. Volunteers with
      artificial or natural nails were artificially contaminated with ground beef
      containing E. coli JM109 or artificial feces containing FCV. Volunteers washed
      their hands with tap water, regular liquid soap, antibacterial liquid soap,
      alcohol-based hand sanitizer gel, regular liquid soap followed by alcohol gel, or
      regular liquid soap plus a nailbrush. The greatest reduction of inoculated
      microbial populations was obtained by washing with liquid soap plus a nailbrush,
      and the least reduction was obtained by rubbing hands with alcohol gel. Lower but
      not significantly different (P > 0.05) reductions of E. coli and FCV counts were
      obtained from beneath artificial than from natural fingernails. However,
      significantly (P < or = 0.05) higher E. coli and FCV counts were recovered from
      hands with artificial nails than from natural nails before and after hand
      washing. In addition, microbial cell numbers were correlated with fingernail
      length, with greater numbers beneath fingernails with longer nails. These results
      indicate that best practices for fingernail sanitation of food handlers are to
      maintain short fingernails and scrub fingernails with soap and a nailbrush when
      washing hands.

PMID- 14672228
TI  - A rapid most-probable-number-based enzyme-linked immunosorbent assay for the
      detection and enumeration of Salmonella Typhimurium in poultry wastewater.
AB  - The rapid and accurate detection and enumeration of low levels of Salmonella
      Typhimurium in food processing facilities are critical components of an effective
      hazard analysis critical control point program. The objective of this study was
      to develop a rapid (8 h) most probable number (MPN)-enzyme-linked immunosorbent
      assay (ELISA) for the detection and enumeration of Salmonella Typhimurium in
      wastewater. The specific objectives were to (i) characterize poly- and monoclonal
      Salmonella Typhimurium-specific antibodies in order to select the most specific
      and sensitive antibody for Salmonella Typhimurium detection, and (ii) validate
      the MPN assay through a correlation between the 8-h MPN-ELISA and the traditional
      48-h Salmonella Typhimurium MPN method in poultry scald water. Poultry scald
      water samples were spiked with 10 and 50 CFU/ml of Salmonella Typhimurium. The
      traditional MPN method used a 48-h enrichment period followed by an analysis,
      while the MPN-ELISA used a 5-h enrichment period followed by a 3-h ELISA
      analysis. No differences (P < 0.05) were found between the traditional MPN and
      the MPN-ELISA, indicating the promise of the MPN-ELISA for the rapid detection
      and enumeration of Salmonella Typhimurium within an 8-h shift. This abbreviated
      assay will permit increased product sampling and more rapid movement of food
      between production and processing, resulting in reduced spoilage and quality
      losses.

PMID- 14672229
TI  - Development of a PCR assay for the detection of animal tissues in ruminant feeds.
AB  - The European Community ban on use of meat and bone meal in ruminant feed, as a
      consequence of the spread of bovine spongiform encephalopathy in Europe, has
      prompted a number of investigations about the possibility of detecting animal
      tissues in feedstuff. In this paper, a study on vertebrate primers, designed in
      the 16S rRNA gene of mitochondrial DNA, is described. These primers were able to
      amplify fragments that contained between 234 and 265 bp. The fragments were
      specific for bovine, porcine, goat, sheep, horse, rabbit, chicken, trout, and
      European pilchard and were confirmed by sequence analysis amplicons. The primers
      were used in a PCR assay applied to five samples of meat and blood meals of
      different species and subjected to severe rendering treatments (134.4 to 141.9
      degrees C and 3.03 to 4.03 bar for 24 min). The presence of vertebrate tissues
      was detected in all samples. The assay proved to be rapid and sensitive
      (detection limit 0.0625%). It can be used as a routine method to detect animal
      derived ingredients in animal feedstuff.

PMID- 14672230
TI  - Fermentation of Vigna sinensis var. carilla flours by natural microflora and
      Lactobacillus species.
AB  - Natural fermentation and an inoculum containing 10% (vol/vol) Lactobacillus
      fermentum or Lactobacillus plantarum were used to obtain fermented flours from
      Vigna sinensis L. var. carilla seeds that had been washed with distilled water
      and dried at 55 degrees C for 24 h. To optimize the fermentation parameters
      (lactic acid bacterium level, bean flour concentration, and fermentation time),
      several small-scale fermentation processes were carried out. On the basis of the
      results obtained, fermentor-scale bean fermentation by microorganisms present on
      the seeds (natural fermentation [NF]) or by inoculation with L. plantarum (PF)
      was carried out at 37 degrees C for 48 h with a concentration of 300 g of bean
      flour per liter. The fermented flours (NF and PF) were also autoclaved. The
      levels of alpha-galactosides, inositol phosphates, trypsin inhibitor activity
      (TIA), soluble carbohydrates, starch (total and available), total available
      carbohydrates, thiamin, and riboflavin were determined for the processed cowpea
      flours, and microbiological studies were also carried out. The beans' levels of
      alpha-galactosides, TIA, and inositol hexaphosphate decreased by 95, 50, and 85%,
      respectively, for the NF flour and by 87, 27, and 85%, respectively, for the PF
      flour, while inositol pentaphosphate and inositol tetraphosphate were present in
      both fermented flours. The sucrose content decreased, and glucose, fructose, and
      galactose appeared as a result of fermentation. The levels of total available
      sugars and thiamin decreased by 2 and 12% and by 69 and 43%, respectively, while
      the riboflavin content increased by 106 and 94% for NF and PF flours,
      respectively. When NF and PF cowpea flours were heated in an autoclave for 20
      min, TIA decreased further (by 80 and 56%, respectively). According to the
      chemical and microbiological results obtained in this study, fermentation with L.
      plantarum and autoclaving is an excellent process by which to produce a new
      functional food from the seed of a cheap legume (Vigna sinensis L. var. carilla).

PMID- 14672231
TI  - Stability of arsenobetaine levels in manufactured baby foods.
AB  - The stability of arsenobetaine in baby foods under different experimental
      conditions is evaluated. Total arsenic was analyzed by electrothermal atomic
      absorption spectrometry, and the speciation of arsenicals was carried out by
      coupling liquid chromatography to hydride generation-atomic absorption
      spectrometry. The highest arsenic levels in the analyzed baby foods corresponded
      to those containing plaice (2 to 3 microg/g). The speciation data indicated that
      arsenobetaine, a nontoxic species, was the only arsenical present in the baby
      foods analyzed at levels between 0.2 and 3 microg/g. Two different procedures for
      extracting arsenicals from baby foods, involving a water-methanol-chloroform
      mixture and enzymatic hydrolysis, were tested, and similar results were obtained.
      Furthermore, the arsenobetaine levels remained unchanged when the baby foods were
      stored for different times or when the samples were freeze-dried, thus confirming
      the stability of arsenobetaine and the nonappearance of other arsenic species by
      interconversion. The reliability of the procedure was checked by analyzing a
      certified reference material.

PMID- 14672232
TI  - Polycyclic aromatic hydrocarbons in foods: human exposure through the diet in
      Catalonia, Spain.
AB  - The dietary intake of 16 polycyclic aromatic hydrocarbons (PAHs) (naphthalene,
      acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene,
      pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene,
      benzo[a]pyrene, dibenz[a,h]anthracene, benzo[g,h,i]perylene, and indeno[1,2,3
      c,d]pyrene) by the general population of Catalonia, Spain, was calculated.
      Concentrations of PAHs in food samples randomly acquired in seven cities of
      Catalonia from June to August 2000 were measured. Eleven food groups were
      included in the study. High-performance liquid chromatography was used to analyze
      PAHs. The dietary intakes of total and carcinogenic PAHs was calculated for five
      population groups: children, adolescents, male adults, female adults, and
      seniors. Among the analyzed PAHs, there was a predominance of phenanthrene (16.7
      microg/kg) and pyrene (10.7 microg/kg). By food group, the highest levels of
      total PAHs were detected in cereals (14.5 microg/kg) and in meat and meat
      products (13.4 microg/kg). The mean estimated dietary intake of the sum of the 16
      PAHs was as follows: male adults, 8.4 microg/day; adolescents, 8.2 microg/day;
      children, 7.4 microg/day; seniors, 6.3 microg/day; female adults, 6.3 microg/day.
      The calculated daily intake of PAHs would be associated with a 5/106 increase in
      the risk for the development of cancer in a male adult with a body weight of 70
      kg.

PMID- 14672233
TI  - Microbiology of charcoal-broiled European river lampreys (Lampetra fluviatilis)
      stored at 3 and 22 degrees C.
AB  - The microbiological quality of 30 production lots of charcoal-broiled river
      lampreys was studied at three lamprey processing plants (plants A, B, and C).
      Samples were taken directly after charcoal broiling and stored at 22 and 3
      degrees C. Lampreys were examined on the day of manufacture, and those kept at 22
      degrees C were examined every second day for 6 days. Samples kept at 3 degrees C
      were examined every fourth day for up to 24 days. On the production day, the mean
      aerobic plate counts (APCs) for broiled lampreys from plants A, B, and C were
      2.29 log CFU/g, 1.88 log CFU/g, and undetectable (1.67 log CFU/g), respectively.
      At 22 degrees C, the mean APCs for samples from plants A, B, and C increased
      markedly within 4 days, and after 6 days the counts for samples from these plants
      were 8.56, 5.04, and 6.23 log CFU/g, respectively. Chilling and storage at 3
      degrees C remarkably improved the shelf life of the product. The levels of
      bacteria in charcoal-broiled river lampreys from plant A were higher than those
      in lampreys from plants B and C. No significant increases in APCs were observed
      during storage at 3 degrees C for 24 days; mean APCs did not exceed 2.80 log
      CFU/g for samples from any plant. Staphylococcus aureus was found in two samples.
      No lactic acid bacteria, thermotolerant coliforms, enterococci, Clostridium
      perfringens, or Listeria monocytogenes was detected. Microbiological data from
      this study will be used for the development of a hazard analysis for the
      determination of critical control points.

PMID- 14672234
TI  - Pectin methyl esterase and natural microflora of fresh mixed orange and carrot
      juice treated with pulsed electric fields.
AB  - The effects of pulsed electric fields (PEFs) on pectin methyl esterase (PME),
      molds and yeast, and total flora in fresh (nonpasteurized) mixed orange and
      carrot juice were studied. The PEF effect was more extensive when juices with
      high levels of initial PME activity were subjected to treatment and when PEF
      treatment (at 25 kV/cm for 340 micros) was combined with a moderate temperature
      (63 degrees C), with the maximum level of PME inactivation being 81.4%. These
      conditions produced 3.7 decimal reductions in molds and yeast and 2.4 decimal
      reductions in total flora. Experimental inactivation data for PME, molds and
      yeast, and total flora were fitted to Bigelow, Hulsheger, and Weibull
      inactivation models by nonlinear regression. The best fit (lowest mean square
      error) was obtained with the Weibull model.

PMID- 14672235
TI  - Validation of guidelines for investigating foodborne disease outbreaks: the
      experience of the Lazio region, Italy.
AB  - Information about risk ratios, exposures, and vehicles for foodborne diseases
      tends to be more reliable when it is obtained from outbreak surveillance than
      when it is obtained from disease notifications. In 1997, guidelines for methods
      of investigating foodborne disease outbreaks (FBDOs) were implemented in the
      Lazio region. To evaluate the impact of these guidelines, we analyzed information
      about 410 FBDOs from 1996 to 2000. Under these guidelines, the delay in the
      reporting of outbreaks decreased from 10 to 2 days. An analysis of 82 large FBDOs
      (in which > 30 people were exposed) showed increases in the calculation of attack
      rates with a cohort approach (up to 83%), correctly drawn epidemic curves (up to
      79%), and the calculation of food-specific relative risk (up to 60%). On the
      other hand, the level of the determination of etiology remained low: tests were
      performed on patients in 57% of the cases considered, resulting in an agent
      identification rate of 38%; for 22 outbreaks, tests were performed on food,
      resulting in three positive identifications. Analysis of the contamination route
      with the use of hazard analysis critical control point criteria a posteriori was
      carried out for 15 outbreaks, and nine of these analyses were successful. The
      implementation of the 1997 guidelines was successful with regard to
      epidemiological and statistical methods but did not improve etiological diagnosis
      for FBDOs. These guidelines improved surveillance for outbreaks in which > 30
      people were exposed in well-defined exposure situations; however, the guidelines
      did not significantly improve epidemiological investigations of small household
      outbreaks.

PMID- 14672236
TI  - Detection and fate of Bacillus anthracis (Sterne) vegetative cells and spores
      added to bulk tank milk.
AB  - A preparation of Bacillus anthracis (Sterne strain) spores was used to evaluate
      commercially available reagents and portable equipment for detecting anthrax
      contamination by using real-time PCR and was used to assess the fate of spores
      added directly to bulk tank milk. The Ruggedized Advanced Pathogen Identification
      Device (RAPID) was employed to detect spores in raw milk down to a concentration
      of 2,500 spores per ml. Commercially available primers and probes developed to
      detect either the protective antigen gene or the lethal factor gene both provided
      easily read positive signals with the RAPID following extraction from milk with a
      commercially available DNA extraction kit. Nucleotide sequence analysis of the
      vrrA gene with the use of DNA extracted from spiked milk provided molecular data
      that readily identified the spores as B. anthracis with a 100% BLAST match to the
      Sterne and Ames strains and easily distinguished them from B. cereus. Physical
      fate and thermal-stability studies demonstrated that spores and vegetative cells
      have a strong affinity for the cream fraction of whole milk. A single treatment
      at standard pasteurization temperatures, while 100% lethal to vegetative cells,
      had no effect on spore viability even 14 days after the treatment. Twenty-four
      hours after the first treatment, a second treatment at 72 degrees C for 15 s
      reduced the viability of the population by ca. 99% but still did not kill all of
      the spores. From these studies, we conclude that standard pasteurization
      techniques for milk would have little effect on the viability of B. anthracis
      spores and that raw or pasteurized milk poses no obstacles to the rapid detection
      of the spores by molecular techniques.

PMID- 14672237
TI  - Use of ozone to reduce molds in a cheese ripening room.
AB  - Cheese ripening rooms have an unusual environment, an environment that encourages
      mold growth. Ozone has been applied in various ways in the food industry. One
      useful advantage of ozone is that it inactivates molds. In this study, a cheese
      ripening room was ozonated, and the effectiveness of this treatment was evaluated
      both in air and on surfaces through sampling on a weekly basis over a 3-month
      period. The results obtained indicate that ozone treatment reduced the viable
      airborne mold load but did not affect viable mold on surfaces. Only by wiping the
      surfaces with a commercial sanitizer was it possible to decrease the viable mold
      load on surfaces. To improve overall hygiene in the ripening room, a combination
      of cleaning regimes is recommended. The mold genera occurring most frequently in
      the air of the cheese ripening room were Penicillium, Cladosporium, and
      Aspergillus, which accounted for 89.9% of the mold isolates. Penicillium and
      Aspergillus were identified to the species level, and data showed that P.
      brevicompactum and P. aurantiogriseum, as well as A. versicolor, were the species
      most frequently isolated.

PMID- 14672238
TI  - Efficacy of a commercial produce wash on bacterial contamination of lettuce in a
      food service setting.
AB  - Many microorganisms (including a number of important foodborne pathogens) can be
      present on raw fruits and vegetables. Since these products are frequently eaten
      raw, any pathogens present represent a potential risk to the consumer. The
      objective of this study was to compare the efficacy of a commercial produce wash
      with that of water for reducing the total bacterial population on lettuce when
      used by food service employees in university dining halls. Because this study was
      carried out in actual food service facilities during their daily operation, we
      used indigenous produce microflora instead of actual pathogens. Over the course
      of the study, more than 40 heads of lettuce were divided into thirds, and each
      section was analyzed for total plate count either before washing, after washing
      in water, or after washing in Victory produce wash. When initial contamination
      levels were > or = 100 CFU/g (n = 36 samples), reductions obtained with Victory
      produce wash (1.8 log CFU/g) were significantly larger (P = 0.0006) than those
      obtained with water (0.8 log CFU/g). Our results indicate that Victory produce
      wash is effective in reducing indigenous flora on lettuce during food service
      preparation. Our results also show that care must be taken in the analysis of
      microbial reduction data: only a slight reduction in total plate count (ca. 0.1
      log CFU/g) and no significant difference in reductions (P = 0.84) were observed
      when all samples (irrespective of initial contamination level) were compared.

PMID- 14672239
TI  - Pathogenicity of food and clinical Listeria monocytogenes isolates in a mouse
      bioassay.
AB  - Serotype distributions of Listeria monocytogenes in clinical samples and foods
      often differ. It is unknown whether such differences reflect a variation in the
      virulence of strains or are due to other factors that are not directly related to
      the strains' ability to cause illnesses. Fifty-two food and eight clinical
      isolates of L. monocytogenes were obtained from France, Japan, and the United
      States. Their pathogenicity in nonimmunocompromised female ICR mice was
      determined by intraperitoneal (i.p.) injection of the mice with test strains at
      10(8) to 10(9) CFU per mouse. Five mice were injected with each Listeria strain
      and observed for 5 days. Listeria isolates that caused at least one death in 5
      days were considered pathogenic. Isolates that caused no deaths in 5 days were
      considered nonpathogenic. All strains except Listeria innocua and one L.
      monocytogenes serotype 4b strain (RM3-1) isolated from bovine raw milk were
      pathogenic to nonimmunocompromised mice. Three food isolates of L. monocytogenes
      serotype 1/2c were weakly pathogenic to nonimmunocompromised mice, killing a
      maximum of 50% of mice at 10(8) CFU. Strains with no pathogenicity or reduced
      pathogenicity were further tested for their pathogenicity to immunocompromised
      mice. Each strain was inoculated i.p. into five mice at 10(3) to 10(10) CFU per
      mouse. No deaths of immunocompromised mice inoculated with 10(8) CFU were
      observed, but 20 to 40% of the mice died when inoculated with 10(9) CFU of L.
      monocytogenes RM3-1. The three L. monocytogenes serotype 1/2c isolates were also
      weakly pathogenic to immunocompromised mice, with two of the three isolates
      killing < or = 60% of mice at doses of < or = 10(8) CFU. The hemolytic activity
      of the three weakly pathogenic serotype 1/2c isolates was similar to that of
      pathogenic strains. However, the nonpathogenic strain RM3-1 was not found to be
      hemolytic on horse blood agar. We have identified several L. monocytogenes
      strains with reduced virulence levels. Further characterization of such isolates
      may aid in understanding factors affecting the variation in virulence among
      strains.

PMID- 14672240
TI  - Detection of Salmonella enterica somatic groups C1 and E1 by PCR-enzyme-linked
      immunosorbent assay.
AB  - Objectives of this study were to develop a PCR-based enzyme-linked immunosorbent
      assay (PCR-ELISA) for identification of Salmonella enterica somatic groups C1 and
      E1 and to evaluate this procedure along with a PCR-ELISA procedure for S.
      enterica somatic groups B, C2, and D in a masked study. Primers were selected
      from the rfb gene cluster, which is responsible for biosynthesis of O antigens of
      Salmonella lipopolysaccharide. Previously serogrouped Salmonella isolates (n =
      169) were used to determine the sensitivity and specificity of the PCR-ELISA
      procedure. DNA from all isolates was amplified using the PCR procedure for
      selected somatic groups and amplified products were visualized on agarose gels,
      as well as subjected to the ELISA procedure. The PCR-ELISA technique correctly
      identified 97% of somatic group C1 and 87% of somatic group E1. The sensitivity
      of this procedure to correctly identify S. enterica somatic group C1 was 97% and
      88% for somatic group E1. The specificity was 98% for both somatic groups C1 and
      E1. The PCR-ELISA techniques correctly identified 93% of Salmonella isolates
      belonging to somatic groups B, C1, C2, D, and E1. The overall sensitivity of this
      procedure to correctly identify S. enterica somatic groups was 96% and the
      specificity was 98%. Ninety-one percent of somatic group D, 92% of somatic group
      B, and 97% of somatic group C2 were identified correctly with this procedure.
      Results of this study indicate that the PCR-ELISA procedure is a rapid and
      accurate method for serogrouping Salmonella isolates. Utilization of the PCR
      ELISA procedure for Salmonella serogrouping would aide in identification,
      surveillance, prevention, and control of Salmonella.

PMID- 14672241
TI  - Significance of nonaromatic organic acids in honey.
AB  - Although organic acids represent < 0.5% of honey's constituents, they make
      important contributions to the organoleptic, physical, and chemical properties of
      honey. To date, approximately 30 nonaromatic organic acids have been identified
      in honey, but relatively little attention has been paid to these components. This
      article reviews the current literature related to the significance of nonaromatic
      organic acids in honey; it was written with a goal of attracting researchers to
      study these interesting honey components. Previous research contributions on
      nonaromatic organic acids in honey may be classified into five main areas: (i)
      the antibacterial activities of these acids, (ii) the antioxidant activities of
      these acids, (iii) the use of these acids as possible indicators of incipient
      fermentation, (iv) the use of these acids for treatment of Varroa infestation,
      and (v) the use of these acids as factors for the characterization of both
      botanical and geographical origins of honeys. We conclude that nonaromatic
      organic acids are of interest for diverse reasons and that there is a particular
      need for studies regarding their possible antibacterial and antioxidant
      activities.

PMID- 14672242
TI  - Neuropsychological investigations of the impulsive personality disorders.

PMID- 14672243
TI  - Socio-economic status, family disruption and residential stability in childhood:
      relation to onset, recurrence and remission of major depression.
AB  - BACKGROUND: Childhood adversity significantly increases the risk of depression,
      but it is unclear whether this risk is most pronounced for depression occurring
      early in life. In the present study, we examine whether three aspects of
      childhood adversity--low socio-economic status (SES), family disruption, and
      residential instability--are related to increased risk of depression during
      specific stages of the life course. We also examine whether these aspects of
      childhood adversity are related to the severity of depression. METHOD: A sample
      of 1089 of the 4140 births enrolled in the Providence, Rhode Island cohort of the
      National Collaborative Perinatal Project was interviewed between the ages of 18
      and 39. Measures of parental SES, childhood family disruption and residential
      instability were obtained upon mother's enrolment and at age 7. Age at onset of
      major depressive episode, lifetime number of depressive episodes, and age at last
      episode were ascertained via structured diagnostic interviews. Survival analysis
      was used to identify risk factors for depression onset and remission and Poisson
      regression was used to model the recurrence rate of depressive episodes. RESULTS:
      Low parental SES, family disruption and a high level of residential instability,
      defined as three or more family moves, were related to elevated lifetime risks of
      depression; the effects of family disruption and residential instability were
      most pronounced on depression onset by age 14. Childhood adversity was also
      related to increased risk of recurrence and reduced likelihood of remission.
      CONCLUSIONS: Childhood social disadvantage significantly influences risk of
      depression onset both in childhood and in adulthood. Early childhood adversity is
      also related to poor prognosis.

PMID- 14672244
TI  - Major depression and cigarette smoking: results of a 21-year longitudinal study.
AB  - BACKGROUND: The aim of this paper was to examine the association between major
      depression and cigarette smoking among young adults in a birth cohort before and
      after adjusting for confounding factors. METHOD: Data were gathered over the
      course of the Christchurch Health and Development Study (CHDS). The CHDS is a
      longitudinal study of a birth cohort of 1265 New Zealand children studied to age
      21. Data were gathered by interview on: (a) major depression over the period 16
      21 years; (h) daily smoking and nicotine dependence over the period from 16-21
      years. In addition, the study included extensive information on social, family,
      and behavioural factors in childhood and adolescence. RESULTS: Young people
      meeting DSM-IV criteria for major depression had elevated rates of daily smoking
      and nicotine dependence. These associations were reduced substantially by control
      for potential confounding child and adolescent factors. Nonetheless, even after
      such control, major depression was associated with increased rates of daily
      smoking (IRR = 1.19; 95% CI = 1.03, 1.39) and elevated rates of nicotine
      dependence (OR = 1.75; 95% CI = 1.13, 2.70). CONCLUSIONS: The results suggest
      that much of the association between smoking and depression reflects common
      confounding factors that are associated with both outcomes. Nonetheless, even
      after control for these factors there is evidence of a possible causal linkage
      between smoking and depression. The direction of causality between smoking and
      depression remains unknown.

PMID- 14672245
TI  - Examining the relationship between pubertal stage, adolescent health behaviours
      and stress.
AB  - BACKGROUND: This paper examines the associations between puberty and three
      important health behaviours (smoking, food intake and exercise) and explores
      whether these associations are mediated by puberty's relationship to stress and
      psychological difficulties. METHOD: Data were taken from the first year of the
      ongoing, 5-year, Health and Behaviours in Teenagers Study (HABITS). This is a
      school-based study set in 36 schools in London. In the first year of the study,
      4320 students (2578 boys, 1742 girls) in their first year of secondary education
      took part. RESULTS: Among girls, being more pubertally advanced was associated
      with a greater likelihood of having tried smoking. Among boys, being more
      pubertally advanced was associated with a greater likelihood of having tried
      smoking, a higher intake of high-fat food and higher levels of exercise. More
      pubertally advanced girls experienced more stress but not more psychological
      difficulties. There were no associations between puberty and either stress or
      psychological difficulties in boys. Stress and psychological difficulties were
      associated with health behaviours in girls and boys, but neither of these factors
      mediated the relationship between pubertal stage and health behaviours found in
      girls. CONCLUSIONS: These results suggest that the onset of puberty has a marked
      effect on the development of health behaviours. Puberty was related to an
      acceleration of the development of unhealthy behaviours, except for exercise
      behaviour in boys, where advanced puberty was associated with more exercise.
      These changes were unrelated to adolescent issues of stress and a causal
      explanation for these associations must be sought elsewhere.

PMID- 14672246
TI  - The effect of a nutritional source of tryptophan on dieting-induced changes in
      brain 5-HT function.
AB  - BACKGROUND: Dieting in healthy women results in a decrease in the availability of
      tryptophan (TRP), the amino-acid precursor of serotonin (5-HT), for brain 5-HT
      synthesis. This is associated with increases in the prolactin response to 5-HT
      drug challenge suggesting a 'supersensitivity' of 5-HT neuroendocrine responses.
      The aim of the study was to assess whether increased TRP intake during dieting
      would prevent the changes in TRP availability and 5-HT neuroendocrine function.
      METHOD: Fifty female subjects underwent a 1000 kcal daily diet for 3 weeks. In
      the final week of the diet subjects were randomly allocated to receive either
      nutritionally-sourced TRP (1.8 g daily) or placebo in a double-blind, parallel
      group, design. RESULTS: TRP supplementation failed to modify the dieting-induced
      reduction in fasting TRP availability to the brain. However, in contrast to
      placebo-treated subjects, subjects receiving additional TRP did not show enhanced
      prolactin responses to intravenous TRP challenge. CONCLUSIONS: The decrease in
      TRP availability produced by dieting may be due to increased TRP metabolism
      rather than decreased TRP intake. While TRP treatment did not increase fasting
      TRP availability it may have modified the effect of dieting on brain 5-HT
      function. Further studies will be needed to see if this effect of TRP has
      consequences for the effectiveness of dieting as means of weight control.

PMID- 14672247
TI  - Ghrelin and leptin responses to food ingestion in bulimia nervosa: implications
      for binge-eating and compensatory behaviours.
AB  - BACKGROUND: Ghrelin and leptin are endogenous peripheral proteins involved in the
      regulation of eating behaviour. In particular, ghrelin stimulates hunger and
      promotes food ingestion, whereas leptin increases satiety and reduces food
      consumption. Therefore, alterations in the physiology of these peptides may play
      a role in the pathogenesis of eating disorders such as bulimia nervosa. In the
      present study, we investigated ghrelin and leptin responses to food ingestion in
      patients with bulimia nervosa. METHOD: Nine symptomatic drug-free bulimic women
      and 12 age-matched healthy women ingested a meal of 1207 kcal (60% carbohydrates,
      23% fat and 17% proteins) at 12.00 a.m. and underwent blood sample collection
      before and 45, 60, 90, 120 and 180 min after the meal. Plasma levels of ghrelin,
      leptin, insulin and glucose were measured. RESULTS: In healthy women, circulating
      ghrelin exhibited a drastic decrease after the food intake whereas, in bulimic
      patients, this response was significantly blunted. No difference between the two
      subjects groups was observed in post-prandial profiles of plasma leptin, insulin
      and glucose. CONCLUSIONS: The lack of a leptin response to food ingestion, in
      both bulimic and healthy women, is compatible with the role of this peptide as
      long-term rather than short-term modulator of eating behaviour. The blunted
      ghrelin response to food ingestion may support the occurrence in bulimic subjects
      of an impaired suppression of the drive to eat following a meal. This may have
      implications for binge-eating.

PMID- 14672248
TI  - The genetic epidemiology of body attitudes, the attitudinal component of body
      image in women.
AB  - BACKGROUND: There were four purposes of the current study, including the
      investigation of the: (i) adequacy of a multidimensional measure of body image;
      (ii) genetic and environmental epidemiology of this measure; (iii) shared
      variance between genetic and environmental risk factors for body mass index (BMI)
      and body image; and (iv) Equal Environment Assumption (EEA) as it related to body
      attitudes. METHOD: Six types of body attitudes, as measured by the Body Attitudes
      Questionnaire (BAQ) and reported by 894 complete female-female twin pairs (mean
      age 32.35 years, S.D. = 41.8) from the Australian Twin Registry, were analysed.
      RESULTS: Confirmatory factor analysis of the BAQ supported the adequacy of the
      measure. Additive genetic and unique environmental influences best accounted for
      the variance of all six of the BAQ subscales. The relationship between BMI and
      body attitudes was primarily due to shared genes rather than environment but the
      majority of genetic and environmental effects on body attitudes were independent
      of BMI, with the exception of the Feeling Fat subscale, which shared 53% of its
      genetic risk factors with BMI. One violation of the EEA was suggested, namely
      similarity of childhood treatment influenced similarity on Lower Body Fatness
      subscale. CONCLUSIONS: Findings support the notion that: (i) body image is a
      multidimensional concept; (ii) it is relatively independent of BMI; and (iii)
      both genetic and non-shared environment are influential determinants of body
      attitudes.

PMID- 14672249
TI  - Pre-morbid characteristics and co-morbidity of methamphetamine users with and
      without psychosis.
AB  - BACKGROUND: The long-term use of methamphetamine (MAMP) can result in psychosis
      but it is not clear why some individuals develop psychotic symptoms, while others
      use MAMP regularly over long periods and remain unscathed. We set out to
      characterize MAMP users and to examine the relationship of pre-morbid
      personality, pre-morbid social function and other psychiatric disorders to MAMP
      psychosis. METHOD: Four hundred and forty-five amphetamine users were recruited
      from a psychiatric hospital and a detention centre in Taipei, and were assessed
      with the Diagnostic Interview for Genetic Studies (DIGS). Their parents were
      interviewed with the Premorbid Schizoid and Schizotypal Traits (PSST) and the
      Premorbid Social Adjustment (PSA) schedules. Pre-morbid characteristics and
      psychiatric co-morbidity were compared between the MAMP users with a lifetime
      diagnosis of MAMP psychosis and those without. RESULTS: The MAMP users with
      psychosis presented a clinical picture which mimicked the positive symptoms of
      schizophrenia: 85% had auditory hallucinations; 71% persecutory delusions; 63%
      delusions of reference. Compared with their non-psychotic counterparts, these
      MAMP users were younger at first MAMP use, used larger amounts of MAMP, had a
      significantly higher mean PSST score, and higher rates of major depressive
      disorder, alcohol dependence and antisocial personality disorder. CONCLUSIONS:
      Earlier and larger use of MAMP was associated with increased risk of psychosis.
      Our data are also compatible with the view that pre-morbid schizoid/schizotypal
      personality predisposes MAMP users to develop psychosis, and that the greater the
      personality vulnerability, the longer the psychosis will persist.

PMID- 14672250
TI  - Attributes of long-term heavy cannabis users: a case-control study.
AB  - BACKGROUND: Although cannabis is the most widely used illicit drug in the United
      States, few recent American studies have examined the attributes of long-term
      heavy cannabis users. METHOD: Using a case-control design, we obtained
      psychological and demographic measures on 108 individuals, age 30-55, who had
      smoked cannabis a mean of 18000 times and a minimum of 5000 times in their lives.
      We compared these heavy users to 72 age-matched control subjects who had smoked
      at least once, but no more than 50 times in their lives. RESULTS: We found no
      significant differences between the two groups on reported levels of income and
      education in their families of origin. However, the heavy users themselves
      reported significantly lower educational attainment (P < 0.001) and income (P =
      0.003) than the controls, even after adjustment for a large number of potentially
      confounding variables. When asked to rate the subjective effects of cannabis on
      their cognition, memory, career, social life, physical health and mental health,
      large majorities of heavy users (66-90%) reported a 'negative effect'. On several
      measures of quality of life, heavy users also reported significantly lower levels
      of satisfaction than controls. CONCLUSION: Both objective and self-report
      measures suggest numerous negative features associated with long-term heavy
      cannabis use. Thus, it seems important to understand why heavy users continue to
      smoke regularly for years, despite acknowledging these negative effects. Such an
      understanding may guide the development of strategies to treat cannabis
      dependence.

PMID- 14672251
TI  - The effects of anxiety, substance use and conduct disorders on risk of major
      depressive disorder.
AB  - BACKGROUND: Major depressive disorder (MDD) is highly co-morbid with other Axis I
      disorders, which commonly precede its onset. We sought to determine the level and
      periods of risk for MDD posed by prior or co-occurring psychiatric disorders.
      METHOD: Using retrospective data from a longitudinal, population-based sample of
      2926 male and 1929 female adult twin subjects, we predicted the hazard rates for
      MDD from a Cox proportional hazards model with same-year or prior onsets of co
      morbid Axis I disorders as time-dependent covariates. RESULTS: All axis I
      disorders studied (generalized anxiety disorder, panic disorder, phobia, alcohol
      dependence, psychoactive substance use disorders and conduct disorder)
      significantly predicted increased risk for developing MDD. The highest hazard
      rates occurred for MDD onsets that co-occurred with those of the co-morbid
      disorder. However, the risk for onset of MDD subsequent to that of prior
      disorders is also significantly increased and remains relatively unchanged over
      time. Although the risk for onset of MDD is significantly higher in women than
      men, this was not explained by gender differences in prior disorder prevalence or
      increased sensitivity in women to the effects of prior disorders on risk for
      depression. CONCLUSIONS: Prior psychiatric disorders are significant risk factors
      for the development of MDD, independent of the length of the intervening period
      between the onset of the first disorder and that of MDD.

PMID- 14672252
TI  - The detection of intentional contingencies in simple animations in patients with
      delusions of persecution.
AB  - BACKGROUND: It has been proposed that delusions of persecution are caused by the
      tendency to over-attribute malevolent intentions to other people's actions. One
      aspect of intention attribution is detecting contingencies between an agent's
      actions and intentions. Here, we used simplified stimuli to test the hypothesis
      that patients with persecutory delusions over-attribute contingency to agents'
      movements. METHOD: Short animations were presented to three groups of subjects:
      (1) schizophrenic patients; (2) patients with affective disorders; and (3) normal
      control subjects. Patients were divided on the basis of the presence or absence
      of delusions of persecution. Participants watched four types of film featuring
      two shapes. In half the films one shape's movement was contingent on the other
      shape. Contingency was either 'intentional': one shape moved when it 'saw'
      another shape; or 'mechanical': one shape was launched by the other shape.
      Subjects were asked to rate the strength of the relationship between the movement
      of the shapes. RESULTS: Normal control subjects and patients without delusions of
      persecution rated the relationship between the movement of the shapes as stronger
      in both mechanical and intentional contingent conditions than in non-contingent
      conditions. In contrast, there was no significant difference between the ratings
      of patients with delusions of persecution for the conditions in which movement
      was animate. Patients with delusions of persecution perceived contingency when
      there was none in the animate non-contingent condition. CONCLUSIONS: The results
      suggest that delusions of persecution may be associated with the over-attribution
      of contingency to the actions of agents.

PMID- 14672253
TI  - Cognitive functioning in young and middle-aged unmedicated out-patients with
      major depression: testing the effort and cognitive speed hypotheses.
AB  - BACKGROUND: Cognitive deficits are common in major depressive disorder, but their
      nature is unclear. The effort hypothesis states that performance on effortful
      tasks is disproportionately impaired compared with the performance on automatic
      tasks. The cognitive speed hypothesis states that depression is characterized by
      cognitive slowness, which is a source of cognitive dysfunctioning. The present
      study investigated both theories in unmedicated adult depressive patients. It was
      also investigated whether the cognitive deficits can be attributed to more
      general physical illness-related factors or specifically to depressive disorder.
      METHOD: Thirty non-psychotic depressive out-patients were compared with 38
      healthy control subjects and 25 patients with severe allergic rhinitis. The
      effects of group on more automatic and more effortful aspects of cognitive tasks
      measuring cognitive speed (Concept Shifting Task, Stroop Colour Word Test, Memory
      Scanning Test) and memory retrieval (Visual Verbal Learning Task, Verbal Fluency
      Test) were evaluated by MANCOVA. Age, sex, education and pre-morbid intelligence
      were treated as covariates. RESULTS: The depressive group had cognitive deficits
      in the automatic processing subtask of the Stroop, memory scanning and memory
      span. Performance on more effortful tasks was not impaired. CONCLUSIONS: Our
      results are more consistent with the cognitive speed hypothesis. Cognitive
      functioning in depressive disorder seems to be characterized by a reduced speed
      of information processing in automatic subtasks.

PMID- 14672254
TI  - Kinematical analysis of emotionally induced facial expressions in patients with
      obsessive-compulsive disorder.
AB  - BACKGROUND; Motor function is deficient in many patients with obsessive
      compulsive disorder (OCD), especially in the face. To investigate subtle motor
      dysfunction, kinematical analysis of emotional facial expressions can be used.
      Our aim was to investigate facial movements in response to humorous film stimuli
      in OCD patients. METHOD: Kinematical analysis of facial movements was performed.
      Ultrasound markers at defined points of the face provided exact measurement of
      facial movements, while subjects watched a humorous movie ('Mr Bean'). Thirty
      four OCD patients (19 male, 15 female; mean (S.D.) age: 35.8 (11.5) years; mean
      (S.D.) total Y-BOCS score: 25.5 (5.9)) were studied in unmedicated state and
      after a 10-week treatment with the SSRI sertraline. Thirty-four healthy controls
      (19 male, 15 female; mean (S.D.) age: 37.5 (13.1) years) were also investigated.
      RESULTS: At baseline, OCD patients showed significantly slower velocity at the
      beginning of laughing than healthy controls and a reduced laughing frequency.
      There was a significant negative correlation between laughing frequency and
      severity of OCD symptoms. Ten weeks later a significant increase of laughing
      frequency and initial velocity during laughing was found. CONCLUSIONS: Execution
      of adequate facial reactions to humour is abnormally slow in OCD patients.
      Susceptibility of OCD patients with regard to emotional stimuli is less
      pronounced than in healthy subjects. This phenomenon is closely correlated to OCD
      symptoms and is state-dependent.

PMID- 14672255
TI  - Competence of mentally ill patients: a comparative empirical study.
AB  - BACKGROUND: This study investigates the competence of patients with dementia,
      depression and schizophrenia to make treatment decisions. The outcome of an
      objective test instrument is presented and compared with clinical assessment of
      competence by the attending physician. METHOD: The MacArthur Competence
      Assessment Tool-Treatment (MacCAT-T), a test instrument to assess abilities in
      different standards of competence, was administered to patients with diagnoses of
      dementia (N = 31), depression (N = 35) and schizophrenia (N = 43). Statistical
      significance of group differences in the MacCAT-T results were tested with the
      chi-square test. The concordance of the test and clinical assessment of
      competence by the attending physician were evaluated by Cohen's kappa
      coefficient. RESULTS: Patients with dementia, as a group, showed significantly
      more often impaired performance than those with schizophrenia who were still more
      impaired than depressed patients. Patients were classified as impaired or not
      depending on the standards used. By combination of all standards substantially
      more patients were classified as impaired than by clinical assessment (67.7 v.
      48.4% of patients with dementia, 20.0 v. 2.9% of patients with depression, 53.5
      v. 18.4% of patients with schizophrenia). CONCLUSIONS: Using different standards
      of competence the study showed substantial differences among patients with
      dementia, depression and schizophrenia. The high proportion of patients
      identified as incompetent raises several ethical questions, in particular, those
      referring to the selection of standards or the definition of cut-offs for
      incompetence. The discrepancy between clinical and formal evaluations points out
      the influence of the used procedure on competence judgements.

PMID- 14672256
TI  - Gender differences in response to differing antidepressant drug classes: two
      negative studies.
AB  - BACKGROUND: A recent US study presented data suggesting that depressed women are
      more likely to respond to selective serotonin reuptake inhibitor (SSRI) than
      tricyclic (TCA) antidepressant drug therapies. We have undertaken replication
      studies in two independent databases. METHOD: We have examined for gender
      differences in SSRI and TCA antidepressant response in both retrospective and
      prospective naturalistic uncontrolled studies, and in subsets of melancholic and
      non-melancholic depressed subjects. As the US study had indicated that women
      under the age of 40 years were particularly likely to show a differential
      response to SSRIs, we examined for age, gender and interactional effects. In
      addition, we examined for differential SSRI and TCA responsiveness in a subset of
      patients who had received drugs from both classes. RESULTS: We failed to find
      evidence of women having a preferential response to SSRI medication or,
      conversely, of men having a superior response to TCA medication. Older age,
      however, was associated with a superior TCA response and younger age with a
      superior SSRI response. CONCLUSION: As few studies have examined for differential
      gender and age effects in response to narrow action and broad action
      antidepressant drugs across major depressive subtypes, gender differential
      effects remain to be established.

PMID- 14672258
TI  - Whither neuropathology?

PMID- 14672259
TI  - Cervical artery dissection, imaging, trauma and causal inference.

PMID- 14672257
TI  - Prospective evaluation of neurological soft signs in first-episode schizophrenia
      in relation to psychopathology: state versus trait phenomena.
AB  - BACKGROUND: Although patients with schizophrenia have increased rates of
      neurological soft signs, few studies have examined prospectively their trait or
      state characteristics in relation to psychopathology. METHOD: In a prospective
      study of 97 patients with first-episode schizophrenia (DSM-IV criteria) we
      assessed neurological soft signs and psychopathology at presentation and at 6
      month follow-up for 73 cases. To establish whether soft signs were associated
      with variations in clinical state, neurological soft signs were measured using
      two validated examinations (Neurological Evaluation Scale and Condensed
      Neurological Examination); psychopathology was assessed using the Positive and
      Negative Syndrome Scale. RESULTS: There was significant improvement in overall
      neurological function, primarily in motor-related and cortical signs, which were
      associated with improvement in psychopathology. Conversely, 'harder' signs were
      unrelated to improvement in psychopathology. CONCLUSIONS: Neurological soft signs
      in schizophrenia are heterogenous. Motor and cortical signs evidence state-like
      characteristics and vary with clinical course, while 'harder' signs evidence more
      static, trait-like characteristics in accordance with a neurodevelopmental basis.

PMID- 14672260
TI  - De-efferentation and de-afferentation in fulminant polyneuropathy: lessons from
      the isolated brain.

PMID- 14672261
TI  - Progress in clinical neurosciences: therapeutic hypothermia in severe traumatic
      brain injury.
AB  - Severe traumatic brain injury (sTBI) is a relatively common problem with few
      therapies proven effective. Despite its use for over 50 years, therapeutic
      hypothermia has not gained widespread acceptance in the treatment of sTBI due to
      conflicting results from clinical trials. This review will summarize the current
      evidence from animal, mechanistic and clinical studies supporting the use of
      therapeutic hypothermia. In addition, issues of rewarming and optimal temperature
      will be discussed. Finally, the future of hypothermia in sTBI will be addressed.

PMID- 14672262
TI  - The electrodiagnosis of ulnar nerve entrapment at the elbow.
AB  - Entrapment of the ulnar nerve at the elbow is the second most common focal
      peripheral neuropathy. Recent advances have facilitated the electrodiagnosis of
      this common nerve entrapment. The goals of electrodiagnosis are to localize ulnar
      nerve dysfunction, confirm that the disturbance is confined to the ulnar nerve,
      and assess the severity of ulnar nerve dysfunction. The goal of this review is to
      highlight the important advances in anatomy, neurophysiology and methodology that
      impact upon the electrodiagnosis of entrapment of the ulnar nerve at the elbow,
      illustrate the limits of electrodiagnosis, and discuss methodological issues that
      may be the subject of further study. Careful attention to elbow position,
      temperature, and conservative estimates of conduction block should be part of
      common practice. Awareness of anatomical variations in structural anatomy,
      anomalous innervation and fascicular arrangement of ulnar nerve fibers are
      required to interpret electrodiagnostic studies accurately. The most reliable
      finding is slowing of the ulnar across-elbow motor nerve conduction velocity to
      less than 50 m/sec while recording from the abductor digiti minimi muscle, and
      should be carefully interpreted in the presence of a polyneuropathy or other
      neurogenic process. Alternative techniques such as relative ulnar slowing in
      different ulnar nerve segments, use of alternative muscles, sensory and mixed
      nerve techniques provide complementary information, and like all nerve conduction
      studies are highly operator-dependent and should be used on a case by case basis.
      Recent studies have focused the electromyographer's attention on the use of
      shorter across-elbow segments (2-5 cm). This may offer a reasonable trade-off
      between sensitivity and measurement error and may result in improved
      electrodiagnosis.

PMID- 14672263
TI  - Motor vehicle accidents: the most common cause of traumatic vertebrobasilar
      ischemia.
AB  - BACKGROUND: Recent media exposure of strokes from chiropractic manipulation have
      focused attention on traumatic vertebrobasilar ischemia. However, chiropractic
      manipulation, while the easiest cause to recognize, is probably not the most
      common cause of this condition. METHODS: We reviewed all consecutive cases of
      traumatic vertebrobasilar ischemia referred to a single neurovascular practice
      over 20 years, from the office files and hospital records. RESULTS: There were 80
      patients whose vertebrobasilar ischemia was attributed to neck trauma. Five were
      diagnosed as due to chiropractic manipulation, but the commonest attributed cause
      was motor vehicle accidents (MVAs), which accounted for 70 cases; one was a
      sports injury, and five were industrial accidents. In some cases neck pain from
      an MVA led to chiropractic manipulation, so the cause may have been compounded.
      In most vehicular cases the diagnosis had been missed, even denied, by the
      neurologists and neurosurgeons initially involved. The longest delay between the
      injury and the onset of delayed symptoms was five years. CONCLUSIONS: Traumatic
      vertebrobasilar ischemia is most often due to MVAs; the diagnosis is often
      missed, in part because of the delay between injury and onset of symptoms and, in
      part, we hypothesize, because of reluctance of doctors to be involved in
      medicolegal cases.

PMID- 14672264
TI  - Imaging of murine brain tumors using a 1.5 Tesla clinical MRI system.
AB  - BACKGROUND: In this study, we investigated the feasibility of using a 1.5 Tesla
      (T) clinical magnetic resonance imaging (MRI) system for in vivo assessment of
      three histopathologically different brain tumor models in mice. METHODS: We
      selected mouse models in which tumor growth was observed in different
      intracranial compartments: Patched+/- heterozygous knock-out mice for tumor
      growth in the cerebellum (n = 5); U87 MG human astrocytoma cells xenografted to
      the frontal lobe of athymic mice (n = 15); and F5 (n = 15) or IOMM Lee (n = 15)
      human malignant meningioma cells xenotransplanted to the athymic mouse skull base
      or convexity. Mice were imaged using a small receiver surface coil and a clinical
      1.5 T MRI system. T1- and fast spin echo T2-weighted image sequences were
      obtained in all animals. Gadolinium was injected via tail vein to better
      delineate the intracranial tumors. Twenty mice were followed by serial MRI to
      study tumor growth over time. In these mice, images were typically performed
      after tumor implantation, and at two week intervals. Mice were euthanized
      following their last imaging procedure, and their tumors were examined by
      histopathology. The histopathological preparations were then compared to the last
      MR images to correlate the imaging features with the pathology. RESULTS: Magnetic
      resonance imaging delineated th tumors in the cerebellum, frontal lobes and skull
      base in all mouse models. The detection of intracranial tumors was enhanced with
      prio administration of gadolinium, and the limit of resolution of brain tumors in
      the mice was 1-2 mm3. Sequential images performed at different time intervals
      showed progressive tumor growth in all animals. The MR images of tumor size and
      location correlated accurately with th results of the histopathological analysis.
      CONCLUSION: Magnetic resonance imaging of murine brain tumors in different
      intracrania compartments is feasible with a 1.5 T clinical MR system and a
      specially designed surface coil. Tumors as small as 1-2 mm3 can be detecte with
      good image resolution. Mice harbouring nascent brain tumors can be followed
      sequentially by serial MR imaging. This may allow for a noninvasive means by
      which tumor growth can be measured, and novel therapies tested without resorting
      to sacrifice of the mice.

PMID- 14672265
TI  - Chlamydia pneumoniae and atherosclerosis following carotid endarterectomy.
AB  - BACKGROUND: Seroepidemiological studies have shown an association between raised
      antibody titres against Chlamydia pneumoniae, and carotid atherosclerosis or
      stroke. However, direct evidence for a causal link between arterial infection
      with C. pneumoniae and carotid disease remains weak. We hypothesized that long
      term follow-up of patients with pathologically-proven arterial C. pneumoniae
      infection might provide further insight into the role of C. pneumoniae in carotid
      atherosclerosis. METHODS: We followed a cohort of 70 carotid endarterectomy
      patients for ipsilateral restenosis, contralateral progression, and all-cause
      mortality (four year median follow-up period). All patients had presence or
      absence of C. pneumoniae in their carotid plaques documented by
      immunohistochemistry after endarterectomy. A survival function was generated and
      the log-rank test was used to assess the difference in survival between subjects
      with and without documented chlamydial infection in their plaque. RESULTS:
      Baseline demographic and cardiovascular risk factors were similar between the two
      groups, and survival analysis demonstrated no difference (p>0.05) in all-cause
      mortality, or all-cause mortality combined with restenosis and progression.
      CONCLUSIONS: Our data finds no causal role for C. pneumoniae in restenosis or
      progression of carotid disease or mortality in this patient population with
      advanced carotid atherosclerosis.

PMID- 14672266
TI  - Dexamethasone for morbidity after subdural electrode insertion--a randomized
      controlled trial.
AB  - BACKGROUND: Invasive monitoring with subdural electrodes (SDE) for investigation
      of medically intractable epilepsy may be associated with undesirable immediate
      postoperative morbidity such as headache, nausea, vomiting, fever, and meningism.
      We undertook to evaluate the potential beneficial role of perioperative
      dexamethasone in reducing these symptoms. METHODS: In a double-blind placebo
      controlled clinical trial 30 patients undergoing SDE insertion were randomized to
      receive either placebo or a course of dexamethasone beginning one hour prior to
      surgery and tapering to discontinue over 72 hours postoperatively. Pain, pain
      relief, nausea, nausea relief, temperature, and meningism were assessed regularly
      in the postoperative period, and analgesic, antipyretic, and antiemetic drug
      requirements were tabulated. RESULTS: One patient was withdrawn from the
      dexamethasone group due to lack of data. With regards to postoperative pain, the
      direction of benefit favoured dexamethasone but a significant treatment by time
      interaction prevented further analysis of treatment effect. The dexamethasone
      group did have significantly lower temperatures and higher nausea relief scores.
      There was no statistically significant difference between the groups with regards
      to pain relief, nausea, and meningism scores. The beneficial effects of
      dexamethasone were delayed in onset, of limited duration, and not uniform over
      the observation period. CONCLUSION: Dexamethasone appears to have a role in
      reducing immediate morbidity following SDE insertion but its effect is not
      uniform in the postoperative period; it appears to be delayed in onset, and of
      limited duration. Further study is necessary to determine the ideal dosing
      schedule.

PMID- 14672267
TI  - Cell-cycle gene expression in lovastatin-induced medulloblastoma apoptosis.
AB  - BACKGROUND: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a key
      rate-limiting enzyme in the mevalonate pathway, which generates precursors both
      for cholesterol biosynthesis and for the production of nonsteroidal mevalonate
      derivatives that are involved in a number of growth-regulatory processes. We have
      reported that lovastatin, a competitive inhibitor of HMG-CoA reductase, not only
      inhibits medulloblastoma proliferation in vitro, but also induces near-complete
      cell death via apoptosis. The mechanism of this phenomenon is unclear. Possible
      involvement of changes in expression of certain cell-cycle related genes led us
      to study some of them in more detail. METHODS: Medulloblastoma cell lines were
      exposed in vitro to lovastatin, and the effects of gene expression changes were
      studied using RT-PCR, antisense oligonucleotide, DNA electrophoresis and Western
      blotting analysis. RESULTS: 1) Levels of total Ras gene mRNA and individual Ras
      gene mRNA are stable in lovastatin treatment in all examined medulloblastoma cell
      lines. 2) Blocking c-myc gene over-expression does not enhance medulloblastoma
      cell sensitivity to lovastatin. 3) Following lovastatin treatment, p16 expression
      exhibits no change, but pronounced increases of p27KIP1 protein are observed in
      all examined cell lines. Lovastatin induces pronounced increases of p21WAF1
      protein only in Daoy and UW228, but not in D283 Med and D341 Med. 4) Following
      lovastatin treatment, increased p53 protein is detected only in D341 Med, and bax
      protein is unchanged in all cell lines. CONCLUSIONS: Lovastatin-induced growth
      inhibition and apoptosis in medulloblastoma are not dependent on the regulation
      of Ras and c-myc gene expression, but may be mediated by p27KIP1 gene expression.
      Lovastatin-induced apoptosis in medulloblastoma is probably p53 independent, but
      p53 and p21WAF1 gene expression may also mediate anti-proliferative effects of
      lovastatin on specific medulloblastoma cell lines.

PMID- 14672268
TI  - "From sheep to babe"--Menkes disease.

PMID- 14672269
TI  - Autosomal dominant spinocerebellar ataxias: an Asian perspective.
AB  - Autosomal dominant cerebellar ataxias, frequently referred to as spinocerebellar
      ataxias (SCAs) have been under intense scientific research limelight since
      expansions of coded CAG trinucleotide repeats were demonstrated to cause several
      dominantly inherited SCAs. The number of new SCA loci has expanded dramatically
      in recent years. At least ten genes have been identified for SCAs 1, 2, 3, 6, 7,
      8, 10, 12, 17, dentatorubral-pallidoluysian atrophy (DRPLA), and six loci
      responsible for SCAs 4, 5, 11,13, 14, and 16 have been mapped. Genetic testing is
      essential for diagnosis due to the overlapping and varied phenotypic features of
      the different SCAs. While there is no effective treatment available, genetic
      counseling is important for addressing the many ethical, social, legal, and
      psychological issues facing SCA patients. Researchers have recently provided
      valuable information on the pathogenesis of the disease and hopefully a cure will
      be available in the near future.

PMID- 14672270
TI  - Incomplete assessment of experimental cytoprotectants in rodent ischemia studies.
AB  - BACKGROUND: Inadequate preclinical testing (e.g., rodent studies) has been partly
      blamed for the failure of many cytoprotectants to effectively treat stroke in
      humans. For example, some drugs went to clinical trial without rigorous
      functional and histological assessment over long survival times. In this study,
      we characterized recent experimental practices in rodent cytoprotection
      experiments to determine whether the limitations of early studies have been
      rectified. METHODS: We identified 138 rodent cytoprotection studies published in
      several leading journals (Journal of Neuroscience, Stroke, Journal of Cerebral
      Blood Flow and Metabolism and Experimental Neurology) for 2000-2002 and compared
      these to those published in 1990. From each study we determined the ischemia
      model, age and sex of the animal, the histological and functional endpoints used,
      and the methodology used to assess intra- and postischemic temperature. RESULTS:
      Ninety-eight percent of recent studies used young adult rodents and most used
      males. Most studies (60%) did not assess functional outcome and survival times
      were often < or = 48 hr (66%) for focal ischemia and < or = 7 days (80%) for
      global ischemia. Over 60% of the experiments relied solely upon rectal
      temperature during ischemia and only 32.6% of ischemia studies measured
      temperature after surgery. The 1990 data were similar. CONCLUSIONS: Many
      investigators ignore the need to assess long-term functional and histological
      outcome and do not accurately represent clinical conditions of ischemia (e.g.,
      use of aged animals). In addition, intra- and postischemic temperature
      measurement and control is frequently neglected or inadequately performed.
      Further clinical failures are likely.

PMID- 14672271
TI  - Early arrest of mental and motor development associated with bilateral
      hippocampal anoxic damage.
AB  - BACKGROUND: Clinical-pathological study of the case of a woman with amentia from
      birth. CASE HISTORY: A 45-year-old woman was institutionalized since the age of
      two and showed no change in 43 years. She did not stand, walk, talk, use her
      hands or comprehend. She was placed in a chair each day. She lacked control of
      bladder and bowel. She showed no mental capability. CASE PATHOLOGY: The brain
      weighed 1250 gm and was normally developed. There were two anoxic-ischemic
      regions of damage. The hippocampus showed extensive damage bilaterally and the
      cerebellum showed watershed infarction bilaterally. CONCLUSION: A perinatal
      anoxic-ischemic episode is suspected. Hippocampal damage was the only finding
      that might explain the failure of mental and motor development. If this
      hypothesis is correct, the function of the human hippocampus is broader than
      currently accepted.

PMID- 14672272
TI  - Sarcomatous change after sellar irradiation in a growth hormone-secreting
      pituitary adenoma.
AB  - BACKGROUND: Although the benefits of radiotherapy for pituitary adenomas are well
      documented, post-irradiation sarcomas of the sella are rarely seen, with only 20
      cases (mainly of fibrosarcoma) reported in the medical literature. METHOD: We
      describe a case of post-irradiation sarcoma five years after surgery followed by
      external-beam irradiation for an extensive and locally invasive growth hormone
      secreting tumor. The patient was subsequently given pegvisomant, an antagonist of
      growth hormone receptor, to control symptoms of growth hormone excess. RESULTS:
      The patient underwent transsphenoidal resection of the recurrent tumor, followed
      by adjuvant chemotherapy. This led to significant relief in the patient's
      symptoms including radiological evidence of tumor shrinkage, but the tumor regrew
      when, owing to dose-limiting toxicity, chemotherapy was stopped. CONCLUSIONS:
      Post-irradiation sarcomas of the pituitary are well-recognized but rare. They
      should be suspected in patients following sellar irradiation who show abrupt
      onset of new symptoms and appropriate radiological findings, and such tumors may
      respond to cytotoxic chemotherapy.

PMID- 14672273
TI  - Subacute sclerosing panencephalitis presenting with unilateral periodic myoclonic
      jerks.
AB  - BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a rare complication of
      measles virus infection. The disease is characterized by behavioural
      abnormalities, intellectual deterioration, motor weakness, and generalized
      myoclonic jerks progressing to coma and death in one to two years in 80% of the
      cases. The myoclonic jerks are associated with characteristic generalized slow
      periodic complexes on electroencephalography (EEG). The symptoms and signs of
      SSPE are frequently quite variable. The clinical course is equally variable and
      difficult to predict. The characteristic periodic myoclonus can rarely occur
      unilaterally particularly in the early stages of the disease. As well, the
      periodic EEG complexes have been reported unilaterally in up to 3% of cases. CASE
      REPORT: A 12-year-old boy, who was seen at a later stage with atypical
      manifestation of myoclonic body jerks confined entirely unilaterally, combined
      with contralateral periodic EEG complexes. One could assume clinically that the
      more diseased hemisphere was responsible for generating the jerks. However, brain
      magnetic resonance imaging revealed asymmetric hemispheric changes suggesting
      that the less neurologically damaged hemisphere is responsible for generating the
      unilateral myoclonic jerks. This has led to the interpretation that the more
      severely damaged hemisphere has lost the neuronal connectivity required to
      generate these periodic myoclonic jerks. CONCLUSIONS: Subacute sclerosing
      panencephalitis may have asymmetric hemispheric involvement, not only early, but
      also in the advanced stages of the disease, which can result in unilateral
      periodic myoclonic jerks.

PMID- 14672274
TI  - Distal mycotic aneurysm of the AICA mimicking intracanalicular acoustic neuroma.
AB  - BACKGROUND: Among cases of cerebellopontine angle lesions, vascular lesions
      involving the internal auditory canal are extremely rare. We report a distal
      fusiform mycotic pseudoaneurysm of the anterior inferior cerebellar artery (AICA)
      that simulated an acoustic neuroma on presentation. METHODS: A 60-year-old woman
      was investigated for recent onset of acute dizziness. Laboratory and radiographic
      investigations are presented, as well as the surgical management of the patient
      and pathological examination of the aneurysm. CONCLUSIONS: An exceptionally rare
      case of distal mycotic intracanalicular pseudoaneurysm of the AICA with
      intraluminal thrombus and fusiform anatomy is described. In our review of the
      literature (1966-present), only five other intracanalicular AICA-aneurysms were
      encountered, none of which were infectious in etiology. The possible
      pathophysiologic mechanisms of distal AICA-aneurysms are discussed along with the
      currently available literature.

PMID- 14672275
TI  - Neuroepithelial cysts presenting with movement disorders: two cases.
AB  - BACKGROUND: The authors present two cases of movement disorders caused by
      neuroepithelial cysts and highlight their management. Neuroepithelial cysts are
      ependymal or epithelial lined fluid collections of unknown etiology within the
      central nervous system parenchyma with no obvious ventricular or subarachnoid
      connection. Most cysts are asymptomatic, however, some present with seizures,
      mass effect, or rarely with movement disorders. CASE REPORTS: The first patient,
      a 27-year-old female, presented with progressive weakness, dystonic posturing,
      tremor, ballismus and choreoathetotic movements of her right upper extremity. Her
      symptoms improved after stereotactic drainage of a neuroepithelial cyst in her
      basal ganglia but recurred within a year. The second case, a 56-year-old female,
      presented with diplopia, nystagmus, gait imbalance and hemiparesis. Her symptoms
      improved after stereotactic drainage of a midbrain neuroepithelial cyst. The cyst
      reaccumulated over the next few years and she became symptomatic with left arm
      tremor and facial weakness. Aspiration was again performed with symptomatic
      improvement for nine months. Her tremor recurred and a cyst access device was
      placed stereotactically. She improved and has remained stable for over a year.
      CONCLUSION: Simple stereotactic drainage of neuroepithelial cysts has a high
      recurrence rate. The authors recommend considering placement of a drainage device
      to facilitate aspiration of the cyst fluid during follow-up, if needed.

PMID- 14672276
TI  - Simulation of brain death from fulminant de-efferentation.
AB  - BACKGROUND: Guillain-Barre syndrome (GBS) classically presents with a subacutely
      evolving areflexic paralysis, with typical laboratory findings of elevated
      cerebrospinal fluid protein and abnormal nerve conduction studies. There is now
      an increasing recognition of GBS variants that differ in clinical presentation,
      prognosis, electrophysiology and presumed pathogenesis. Fulminant cases of GBS
      have been reported in which a rapid deterioration evolves to a clinical state
      resembling "brain death". METHODS: A retrospective analysis of two such cases of
      fulminant neuropathy are described, that includes the clinical course,
      electrophysiology and neuropathology where available. RESULTS: We describe two
      patients that presented with a rapid course of neurological deterioration,
      lapsing into what resembled a "clinically brain-dead" state that was subsequently
      ascribed to a fulminant polyneuropathy. Investigations (electrophysiological,
      pathological) and the clinical course suggested an axonal neuropathy.
      CONCLUSIONS: A fulminant neuropathy can result in a clinical state resembling
      "brain death" through diffuse de-efferentation. Although generally attributed to
      aggressive demyelination with secondary axonal degeneration, a primary axonopathy
      can also lead to a similar clinical presentation.

PMID- 14672277
TI  - Endogenous oxytocin excites phasic contraction of gallbladder in rabbits through
      oxytocin receptor.
AB  - These experiments were performed to study the effect of oxytocin (OT) and it's
      specific receptor on gallbladder motility in rabbits. The fasted New Zealand
      white rabbits (2.0-2.5 kg) were anaesthetized by urethane (1 g/kg). The
      gallbladder pressure was recorded continuously to monitor the gallbladder
      motility. Systemic OT (0.01, 0.02, 0.04 mg/kg, iv) did not affect the gallbladder
      pressure, but dose-dependently increased the frequency of phasic contraction.
      Five min after OT administration (0.04 mg/kg, iv), the strength of phasic
      contraction increased to 0.23 +/- 0.08 mmHg/min (P < 0.01, n = 6). The
      gallbladder motility returned to normal 15 min later after OT treatment.
      Intravenous injection of atosiban (0.04 mg/kg, iv), an OT receptor antagonist,
      decreased the strength of gallbladder phasic contraction but did not affect
      gallbladder pressure. Pretreatment of atosiban (0.04 mg/kg, iv) completely
      abolished the systemic OT effect on gallbladder. Vasopressin (VP) (0.1 - 0.5
      IU/kg, iv) dose-dependently decrease the gallbladder pressure but did not affect
      the phasic contraction. MK-329 (0.4 mg/kg, iv), the CCK-A receptor antagonist, L
      365, 260 (0.4 mg/kg, iv), the CCK-B receptor antagonist and atropine (0.2 mg/kg,
      iv), the M receptor antagonist, did not affect the OT effect on gallbladder
      motility. We suggest that endogenous OT regulates gallbladder phasic contraction
      through specific OT receptor. This effect is independent of the peripheral CCK
      and M receptors.

PMID- 14672278
TI  - Relative and combined effects of estradiol and prolactin on corticosterone
      secretion in ovariectomized rats.
AB  - In vivo and in vitro experiments were designed to assess the relationship of the
      estradiol (E2) and prolactin (PRL) on glucocorticoid secretion in ovariectomized
      (Ovx) rats. Female rats were Ovx for two weeks and then subcutaneously injected
      with oil or estradiol benzoate (EB) for 3 days before experimentation. Venous
      blood samples were collected from right jugular vein at 0, 30, 60, 90, and 120
      min after challenge with adrenocorticotropin (ACTH). Adrenal zona fasciculata
      reticularis (ZFR) cells from Ovx rats were isolated and incubated with E2 or PRL.
      In the morning and afternoon, EB enhanced the basal and ACTH-stimulated
      concentrations of plasma corticosterone (CORT) and PRL. Administration of E2 in
      vitro increased the basal and ACTH-stimulated release of CORT and production of
      adenosine 3', 5'-cyclic monophosphate (cAMP) in ZFR cells. E2 enhanced the
      forskolin-stimulated release of CORT by ZFR cells. However, the 3-isobutyl-l
      methylxanthine (IBMX)- or 8-Br-cAMP-stimulated release of CORT was not affected
      by E2. E2 augmented the lower doses of PRL-stimulated release of CORT and cAMP
      accumulation as compared with the PRL-treated group alone. Incubation of higher
      doses of PRL increased the production of cAMP. Administration of nifedipine and
      R(+) BK8644 (classic L-type Ca2+ channel blocker) significantly attenuated the
      PRL-stimulated release of CORT. Taken together, these data indicate that E2- and
      PRL-related increase of CORT in Ovx rats is associated with the increase of cAMP
      accumulation and calcium influx in ZFR cells. In conclusion, E2 and PRL play a
      stimulatory role in the co-regulation of CORT secretion.

PMID- 14672279
TI  - The association of a cystatin C gene polymorphism with late-onset Alzheimer's
      disease and vascular dementia.
AB  - A polymorphism in the cystatin C (CST3) gene was suggested to associate with
      Alzheimer's disease (AD). In the present study we attempted to determine the
      association between CST3 polymorphism and AD or vascular dementia (VD), and
      whether such effects are dependent of the APOE4 allele. The polymorphisms of CST3
      genotype were determined using polymerase chain reactions (PCR) followed by gel
      electrophoresis in 124 AD, 70 VD, and 115 control individuals. No statistical
      difference in CST3B allele frequencies was observed among all three groups.
      Associations between CST3B/B genotype and AD patients older than 75-year-old, or
      VD patients younger than 75-year-old were evident. The APOE4 allele alone
      significantly increased the odds for the developing AD, but not VD. A logistic
      regression analysis revealed that either CST3 or its interaction with APOE4 were
      not significant predictors of AD. However, a synergistic association of CST3 and
      APOE4 alleles was observed in predicting VD patients. These results suggest that
      CST3 might interact with APOE4 on conferring vascular pathologies.

PMID- 14672280
TI  - Effect of gossypol on intracellular Ca2+ regulation in human hepatoma cells.
AB  - Gossypol is a natural toxicant present in cottonseeds, and is hepatotoxic to
      animals and human. The effect of gossypol on cytosolic free Ca2+ levels ([Ca2+]i)
      in HA22/VGH human hepatocytes was explored using fura-2 as a fluorescent Ca2+
      indicator. Gossypol increased [Ca2+]i in a concentration-dependent manner with an
      EC50 value of 2 microM. The Ca2+ signal was reduced by removing extracellular
      Ca2+ or by 10 microM La3+, but was not affected by nifedipine, verapamil or
      diltiazem. Pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca2+
      pump inhibitor) to deplete the endoplasmic reticulum Ca2+ partly reduced 10
      microM gossypol-induced Ca2+ release; and conversely pretreatment with gossypol
      abolished thapsigargin-induced Ca2+ release. The Ca2+ release induced by 10
      microM gossypol was not changed by inhibiting phospholipase C with 2 microM
      U73122 or by depleting ryanodine-sensitive Ca2+ stores with 50 microM ryanodine.
      Together, the results suggest that in human hepatocytes, gossypol induced a
      [Ca2+]i increase by causing store Ca2+ release from the endoplasmic reticulum in
      a phospholipase C-independent manner, and by inducing Ca2+ influx.

PMID- 14672281
TI  - Voice low tone to high tone ratio--a new index for nasal airway assessment.
AB  - There are several methodology based on voice analysis to evaluate nasal airway.
      Here we introduce a new quantitative index based on voice spectrum analysis to
      evaluate nasal obstruction. Ten subjects of nasal blockage were instructed to
      produced the sustained consonant-vowel syllable /m partial partial differential/
      at comfortable levels of speech for at least 5 seconds. After nasal decongestant
      treatment, the second voice sample was collected. Sound spectrum was obtained by
      the algorithm of fast Fourier transform and the fundamental frequency (F0) was
      calculated by the method of autocorrelation. Voice low tone to high tone ratio
      (VLHR) was defined as the division of low frequency power (LFP) into high
      frequency power (HFP) of the sound power spectrum and was finally expressed in
      decibels. The cut-off frequency was the product of F0 and square root of (4 x 5).
      The VLHR after nasal decongestant treatment increased significantly as compared
      with that before treatment (P < 0.01). VLHR is a new index derived from sound
      spectral analysis and that may detect the changes in frequency characteristics of
      voice during treatment for nasal obstruction. The index is quantitative, non
      invasive, and potentially useful for basic researches and clinical applications.

PMID- 14672282
TI  - Homocysteine altered ROS generation and NO accumulation in endothelial cells.
AB  - Mild hyperhomocysteinemia (HHcy) is a risk factor for vascular disease and is
      closely associated with endothelial dysfunction. Oxidative stress and decreased
      nitric oxide (NO) bioavailability were reported in HHcy-induced vascular injury;
      however, the exact relationship is not understood. We thus directly determine the
      production of reactive oxygen species (ROS) and NO in cultured endothelial cells
      (HUVECs) to demonstrate the correlated variation between ROS and NO induced by
      Hcy (homocysteine), Cys (cysteine), another thiol compound, and Met (methionine),
      precursor of HHcy in animal study. HUVECs were treated with Hcy, Cys, or Met for
      0.5 or 22-24 h; ROS generation was detected by DCF fluorescence with flow
      cytometry and NO by chemiluminescence. In non-cytotoxic (<1.0 mM) concentration
      ranges, Met exerted no effects on either ROS production or NO concentration, Cys
      decreased ROS production and increased NO in both short-term (0.5 h) and long
      term (22-24 h) treatments; Hcy, however, induced a biphasic effect on ROS
      production, i.e., inhibitory at 0.5 h but stimulatory at 24 h. The maximal
      stimulation by Hcy (0.25 mM) was significantly reduced by co-incubation (12 h)
      with estrogen (1 microM). Hcy caused an early (0.5 h) increase of medium NO which
      was absent in long-term Hcy treatment. The oxidative stress caused by long-term
      Hcy incubation could be ameliorated by estrogen, consistent with earlier in vivo
      observations that estrogen prevents HHcy-induced injury.

PMID- 14672283
TI  - Electrical conduction through nerve and DNA.
AB  - The aim of the present study was to analyse electric resistivity at different
      ambient temperatures between 300 to 20K in the frog sciatic nerve and salmon
      sperm DNA. When the electrical contacts were leaned just into the sciatic nerve,
      an increase of the sciatic nerve resistivity was observed for 240 K < T < 300 K
      and a rise of electrical conductivity was apparent below 240 K. This dependence
      is generally associated with a semiconductor behaviour. Once the sciatic nerve
      temperature was driven below 250K, the resistivity abruptly decreased and then at
      temperatures lower than 234 K, it remained constant and close to one tenth of its
      ambient temperature value. By contrast, when the electrical contacts were leaned
      into Salmon sperm DNA, the resistivity remained constant between 300K to 20K,
      showing a high electrical stability at low temperature. Thus, we report the
      existence of a new form of electric conductivity in the sciatic nerve at low
      ambient temperature, which in turn has many electric similarities with inorganic
      or organic superconductors, whereas temperature failed to alter DNA electrical
      properties until 20K.

PMID- 14672284
TI  - Interventions for micronutrient deficiency control in developing countries: past,
      present and future.
AB  - There has been an evolution in our understanding of the causes of undernutrition
      and of the nutrition intervention programs that should be prioritized. This
      article discusses why nutrition programs have shifted their primary emphasis from
      control of protein deficiency, to energy deficiency, and now to micronutrient
      deficiencies. It has become recognized by the nutrition community that
      micronutrient malnutrition is very widespread, and is probably the main
      nutritional problem in the world. The most commonly used strategies for
      micronutrient deficiency control are supplementation and fortification, because
      they are cost-effective and to some extent, relatively easy to deliver. They have
      important limitations, however. Relatively little emphasis has been placed on
      food-based approaches to control micronutrient malnutrition. Evidence from
      several past studies, including the Nutrition Collaborative Research Support
      Program (N-CRSP), indicated a strong positive association between animal source
      food (ASF) intake, micronutrient status, and many human functions. This
      association motivated the intervention studies supported by the Global Livestock
      CRSP and described in this supplement, which found benefits of increasing ASF
      intake. In contrast to the common assumption that increasing consumption of ASF
      in poor communities is infeasible, and will only cause environmental problems,
      the articles in this supplement show the potential economic benefits of animal
      ownership in poor communities, and provide examples of innovative programs that
      have increased local production and consumption. Much more communication is
      needed among the nutrition, agriculture and development communities to achieve
      improved dietary quality for poor populations.

PMID- 14672285
TI  - Providing micronutrients through food-based solutions: a key to human and
      national development.
AB  - To alleviate poverty in developing countries, economies must grow. Without the
      necessary investments in human capital, national economic growth may not lead to
      poverty alleviation and socioeconomic development, nor be sustainable. Economic
      growth that leads to poverty alleviation is fueled by the creative and physical
      capacities of people. The impact of micronutrient malnutrition is established
      early in life, leading to growth stunting, lower cognitive abilities, lethargy
      and poor attention, and greater severity and rates of infection. These effects
      limit educational progress, physical work capacity and life expectancy, thereby
      reducing individual lifetime productivity and the aggregate ability of the
      population to enhance its well-being and participate in national and global
      markets. The diets of the poor are largely cereal-based, monotonous and lacking
      in diversity and micronutrients. Animal source foods (ASF) have been an important
      factor in human evolution, a component of what was an historically diverse diet
      and an important source of micronutrients. Poverty and micronutrient malnutrition
      positively influence each other. This poverty micronutrient malnutrition (PMM)
      trap requires outside inputs to change the state of development in developing
      countries. Nutrition interventions have been excellent investments in
      development. More productive interaction between agricultural scientists and
      nutritionists, supported by a strong federal agenda for development, is needed to
      break the PMM trap. In the end, food is the means by which nutrients are
      delivered. Food-based approaches will require long-term commitments, but are more
      likely to be sustainable because they are part of a development process that
      leads to long-term economic growth.

PMID- 14672286
TI  - The critical role played by animal source foods in human (Homo) evolution.
AB  - Wild primates take most of the daily diet from plant sources, eating moderate to
      small amounts of animal source foods (ASF). Plant materials make up from 87% to
      >99% of the annual diet of great apes, the closest living relatives of modern
      humans (Homo sapiens sapiens). Reflecting their close genetic relationship, gut
      form and nutrient requirements of apes and humans (Hominoidea) are very similar,
      as is their pattern of digestive kinetics-one predicated on a relatively slow
      turnover of ingesta. In plant-eating mammals, in contrast to carnivorous mammals,
      greater body size is associated with lower dietary quality. Turning to ASF as a
      routine rather than occasional dietary component would have permitted the
      evolving human lineage to evade the nutritional constraints placed on body size
      increases in apes. Without routine access to ASF, it is highly unlikely that
      evolving humans could have achieved their unusually large and complex brain while
      simultaneously continuing their evolutionary trajectory as large, active and
      highly social primates. As human evolution progressed, young children in
      particular, with their rapidly expanding large brain and high metabolic and
      nutritional demands relative to adults would have benefited from volumetrically
      concentrated, high quality foods such as meat. Today, many humans, particularly
      those in high income nations, have a variety of high quality, non-ASF dietary
      alternatives, but such foods were not generally available to paleolithic human
      ancestors nor to many people today in low income nations.

PMID- 14672287
TI  - Animal source foods and human health during evolution.
AB  - Animal source foods (ASF) have always been a constituent of human diets. Their
      pattern of use, however, changed in dramatic ways over the course of human
      evolution. Before 2 million years ago (mya), meat in particular was acquired
      opportunistically via hunting of small or young animals and scavenging of animals
      killed by other species. At some point after that time, humans began to hunt
      cooperatively, making possible the acquisition of meat from large game. The
      marked increase in human heights between 2.0 and 1.7 mya may be linked to more
      efficient means of acquiring meat, namely through hunting. The final pattern of
      meat (and other ASF) use before the modern era is associated with the shift from
      hunting and gathering beginning approximately 10,000 y ago. This fundamental
      dietary change resulted in a narrowing of diet, reduced consumption of meat and
      increased focus on domesticated grains. The study of archaeological human remains
      from around the world reveals that this period in human dietary history saw a
      decline in health, including increased evidence of morbidity (poorer dental
      health, increased occlusal abnormalities, increased iron deficiency anemia,
      increased infection and bone loss). Human populations living in developing and
      developed settings today rely on meats with lipid compositions that when eaten in
      excess promote cardiovascular disease. As humans become more sedentary and eat
      more high fat foods, we can expect to see increases in heart disease,
      osteoporosis and other diseases of "civilization."

PMID- 14672288
TI  - Dynamics of the nutrition transition toward the animal foods sector in China and
      its implications: a worried perspective.
AB  - Many changes in diet and in physical activity are occurring simultaneously in the
      developing world. These diet shifts include large increases in energy density, in
      the proportion of the population consuming a high fat diet and in animal product
      intake. Animal source foods (ASF) play a major role in these diet shifts. This
      article documents the large shifts in the composition of diets and obesity across
      the developing world and notes that these changes are accelerating. Using China
      as a case study, evidence of the speeding up of this process is presented in
      descriptive and more rigorous dynamic longitudinal analysis. The implications of
      these changes for dietary and obesity patterns and cardiovascular disease are
      great. Indeed, developing countries are at a point where the prevalence of
      obesity is greater than that of undernutrition and concerns related to intake of
      saturated fat and energy imbalance must be considered more seriously by the
      agriculture sector. Current agriculture development policy in many developing
      countries focuses on livestock promotion and does not consider the potential
      adverse health consequences of this strategy. Although linkages between ASF
      intake and obesity cannot be established as clearly as they are for high ASF
      intakes, heart disease and cancer, the potential adverse health effects linked
      with an increased ASF intake should no longer be ignored.

PMID- 14672289
TI  - Rising consumption of meat and milk in developing countries has created a new
      food revolution.
AB  - People in developing countries currently consume on average one-third the meat
      and one-quarter of the milk products per capita compared to the richer North, but
      this is changing rapidly. The amount of meat consumed in developing countries
      over the past has grown three times as much as it did in the developed countries.
      The Livestock Revolution is primarily driven by demand. Poor people everywhere
      are eating more animal products as their incomes rise above poverty level and as
      they become urbanized. By 2020, the share of developing countries in total world
      meat consumption will expand from 52% currently to 63%. By 2020, developing
      countries will consume 107 million metric tons (mmt) more meat and 177 mmt more
      milk than they did in 1996/1998, dwarfing developed-country increases of 19 mmt
      for meat and 32 mmt for milk. The projected increase in livestock production will
      require annual feed consumption of cereals to rise by nearly 300 mmt by 2020.
      Nonetheless, the inflation-adjusted prices of livestock and feed commodities are
      expected to fall marginally by 2020, compared to precipitous declines in the past
      20 y. Structural change in the diets of billions of people is a primal force not
      easily reversed by governments. The incomes and nutrition of millions of rural
      poor in developing countries are improving. Yet in many cases these dietary
      changes also create serious environmental and health problems that require active
      policy involvement to prevent irreversible consequences.

PMID- 14672290
TI  - Operationalizing dietary diversity: a review of measurement issues and research
      priorities.
AB  - Dietary diversity (DD) is universally recognized as a key component of healthy
      diets. There is still, however, a lack of consensus on how to measure and
      operationalize DD. This article reviews published literature on DD, with a focus
      on the conceptual and operational issues related to its measurement in developing
      countries. Findings from studies of the association between DD and individual
      nutrient adequacy, child growth and/or household socioeconomic factors are
      summarized. DD is usually measured using a simple count of foods or food groups
      over a given reference period, but a number of different groupings,
      classification systems and reference periods have been used. This limits
      comparability and generalizability of findings. The few studies that have
      validated DD against nutrient adequacy in developing countries confirm the well
      documented positive association observed in developed countries. A consistent
      positive association between dietary diversity and child growth is also found in
      a number of countries. Evidence from a multicountry analysis suggests that
      household-level DD diversity is strongly associated with household per capita
      income and energy availability, suggesting that DD could be a useful indicator of
      food security. The nutritional contribution of animal foods to nutrient adequacy
      is indisputable, but the independent role of animal foods relative to overall
      dietary quality for child growth and nutrition remains poorly understood. DD is
      clearly a promising measurement tool, but additional research is required to
      improve and harmonize measurement approaches and indicators. Validation studies
      are also needed to test the usefulness of DD indicators for various purposes and
      in different contexts.

PMID- 14672291
TI  - Micronutrient deficiencies and cognitive functioning.
AB  - The relationship between four micronutrient deficiencies (iodine, iron, zinc and
      vitamin B-12) and children's cognitive functioning is reviewed. Iodine deficiency
      during pregnancy has negative and irreversible effects on the developing fetus.
      Although there is some evidence that postnatal iodine deficiency is associated
      with cognitive deficits, the findings are controversial. Iron deficiency is
      widespread and has been associated to cognitive deficits, but the results of
      prevention trials are inconsistent. Zinc deficiency has been linked with low
      activity and depressed motor development among the most vulnerable children.
      Associations with cognitive development are less clear and may be limited to
      specific neuropsychological processes. Vitamin B-12 deficiency has been
      associated with cognitive problems among the elderly, but little is known about
      its effect on children's cognitive functioning. Rates of vitamin B-12 deficiency
      are likely to be high because animal products are the only source of vitamin B
      12. Although micronutrient deficiencies often co-occur in the context of poverty,
      little is known about the impact of multiple micronutrient deficiencies on
      cognitive development.

PMID- 14672292
TI  - Nutritional importance of animal source foods.
AB  - Animal source foods can provide a variety of micronutrients that are difficult to
      obtain in adequate quantities from plant source foods alone. In the 1980s, the
      Nutrition Collaborative Research Support Program identified six micronutrients
      that were particularly low in the primarily vegetarian diets of schoolchildren in
      rural Egypt, Kenya and Mexico: vitamin A, vitamin B-12, riboflavin, calcium, iron
      and zinc. Negative health outcomes associated with inadequate intake of these
      nutrients include anemia, poor growth, rickets, impaired cognitive performance,
      blindness, neuromuscular deficits and eventually, death. Animal source foods are
      particularly rich sources of all six of these nutrients, and relatively small
      amounts of these foods, added to a vegetarian diet, can substantially increase
      nutrient adequacy. Snacks designed for Kenyan schoolchildren provided more
      nutrients when animal and plant foods were combined. A snack that provided only
      20% of a child's energy requirement could provide 38% of the calcium, 83% of the
      vitamin B-12 and 82% of the riboflavin requirements if milk was included. A
      similar snack that included ground beef rather than milk provided 86% of the zinc
      and 106% of the vitamin B-12 requirements, as well as 26% of the iron
      requirement. Food guides usually recommend several daily servings from animal
      source food groups (dairy products and meat or meat alternatives). An index that
      estimates nutrient adequacy based on adherence to such food guide recommendations
      may provide a useful method of quickly evaluating dietary quality in both
      developing and developed countries.

PMID- 14672293
TI  - The need for animal source foods by Kenyan children.
AB  - Food intake and dietary patterns in Kenyan households have been studied since the
      1920s. Reports on breastfeeding, nutrient intake, micronutrient deficiencies and
      the impacts of malaria and intestinal parasites on nutritional status are
      reviewed. Diets are mainly cereal-based, with tubers and a variety of vegetables
      and fruits when available. White maize, sorghum and millet are high in phytate
      and fiber, which inhibit the absorption of micronutrients such as zinc and iron.
      Communities growing cash crops have little land for food crops. Although
      households may own cattle, goats and poultry, commonly these are not consumed.
      Adults in nomadic communities consume more meat than nonpastoralists. Lakeside
      and oceanside communities do not consume adequate amounts of fish. Poor
      households have a limited capacity to grow and purchase food, therefore they have
      more nutrient deficiencies. Early weaning to cereal porridge deprives the infant
      of protein and other nutrients from human milk. Other milk is consumed only in
      small amounts in sweetened tea. Older children eat adult diets, which are
      extremely bulky and hard to digest. Anemia is mainly due to iron deficiency,
      malaria and intestinal parasites. In general, Kenyan children have inadequate
      intakes of energy, fat and micronutrients such as calcium, zinc, iron, riboflavin
      and vitamins A and B-12. The multiple micronutrient deficiencies may contribute
      to early onset of stunting and poor child development, whereas lack of calcium
      together with vitamin D deficiency are responsible for the resurgence of rickets.
      There is an urgent need to increase the intake of animal source foods by Kenyan
      children.

PMID- 14672294
TI  - Animal source foods improve dietary quality, micronutrient status, growth and
      cognitive function in Kenyan school children: background, study design and
      baseline findings.
AB  - A previous longitudinal three-country study in Egypt, Kenya and Mexico found
      significant positive associations between intake of animal source foods (ASF) and
      growth, cognitive development and physical activity. To test for a causal
      relationship, a controlled school feeding intervention study was designed to test
      the hypotheses that ASF would improve micronutrient status, growth and cognitive
      function in Kenyan primary school children. Twelve rural Kenyan schools with 554
      children were randomized to four feeding interventions using a local vegetable
      stew as the vehicle. The groups were designated as Meat, Milk, Energy and
      Control, who received no feedings. Feeding was carried out on school days for
      seven terms during 21 mo. Preintervention baseline measures included nutritional
      status, home food intake, anthropometry, biochemical measures of micronutrient
      status, malaria, intestinal parasites, health status and cognitive and behavioral
      measures. The measurements of each child were repeated at intervals over 2 y.
      Baseline data revealed stunting and underweight in approximately 30% of children
      and widespread inadequate intakes and/or biochemical evidence of micronutrient
      deficiencies, particularly of iron, zinc, vitamins A and B-12, riboflavin and
      calcium. Little or no ASF were eaten and fat intake was low. Malaria was present
      in 31% of children, and hookworm, amebiasis and giardia were widely prevalent.
      The outcomes measured were rates of change or increase during the intervention in
      cognitive function, growth, physical activity and behavior and micronutrient
      status. Hierarchical linear random effects modeling was used for analysis of
      outcomes.

PMID- 14672295
TI  - School snacks containing animal source foods improve dietary quality for children
      in rural Kenya.
AB  - Provision of a snack at school could help alleviate the micronutrient
      malnutrition that is common among schoolchildren in developing countries. The
      Child Nutrition Project was designed to compare the efficacy of three school
      snacks in improving growth and cognitive function of children in rural Kenya. The
      snacks provided approximately 20% of the children's energy requirement, and were
      composed of equicaloric portions of githeri (a vegetable stew) alone (Energy
      group), githeri plus milk (Milk group) or githeri plus meat (Meat group). A
      fourth group of children served as Controls. When nutrient intakes from three, 24
      h dietary recalls collected before feeding were compared to three, 24-h recalls
      conducted after feeding began, intakes of vitamin B-12, riboflavin, vitamin A and
      calcium increased more in the Milk group than in the Control group, whereas
      intakes of vitamin B-12, vitamin A, calcium, available iron and available zinc
      increased more than those of Controls for children in the Meat group. At most of
      the time points examined, total energy intake increased more for the Meat group
      than for the other two feeding groups, because the additional energy provided by
      the Milk and Energy snacks was partially balanced by a decrease in the energy
      content of foods consumed at home. This decrease did not occur to the same extent
      for the Meat group, so both dietary quantity and dietary quality improved. For
      the Milk group, only dietary quality improved. For the Energy group, there were
      no significant changes in the total day's diet compared to the Control group.

PMID- 14672296
TI  - Food supplements have a positive impact on weight gain and the addition of animal
      source foods increases lean body mass of Kenyan schoolchildren.
AB  - Observational studies of dietary patterns and growth and studies with milk
      supplementation have shown that children consuming diets containing animal source
      foods grow better. This study evaluates the growth of 544 Kenyan schoolchildren
      (median age 7.1 y) after 23 mo of food supplementation with a meat, milk or
      energy supplement (approximately 1255 kJ) compared to a control group without a
      supplement. Multivariate analyses controlled for covariates compared gain in
      weight, height, weight-for-height Z-score (WHZ), height-for-age Z-score (HAZ),
      mid-upper-arm circumference, triceps and subscapular skinfolds, mid-upper-arm
      muscle and mid-upper-arm fat area. Children in each of the supplementation groups
      gained approximately 0.4 kg (10%) more weight than children in the Control group.
      Children in the Meat, Milk and Energy groups gained 0.33, 0.19 and 0.27 cm more,
      respectively, in mid-upper-arm circumference than children in the Control group.
      Children who received the Meat supplement gained 30-80% more mid-upper-arm muscle
      area than children in the other groups, and children who received the milk
      supplement gained 40% more mid-upper-arm muscle area than children who did not
      receive a supplement. No statistically significant overall effects of
      supplementation were found on height, HAZ, WHZ or measures of body fat. A
      positive effect of the milk supplement on height gain could be seen in the
      subgroup of children with a lower baseline HAZ (< or = -1.4). The results
      indicate that food supplements had a positive impact on weight gain in the study
      children and that the addition of meat increased their lean body mass.

PMID- 14672297
TI  - The impact of dietary intervention on the cognitive development of Kenyan school
      children.
AB  - Previous observational studies in developing countries have suggested that diet
      quality, particularly increased animal source food (ASF) consumption, is
      positively associated with child cognitive development. This report presents
      findings from a study in rural Kenya, designed to test the impact of three
      different diets on the cognitive development of school children. Twelve schools
      with a total of 555 Standard 1 children (equivalent to U.S. Grade 1) were
      randomized to one of four feeding interventions: Meat, Milk, Energy or Control
      (no feeding). Feeding continued for seven school terms (21 mo), and cognitive
      tests were administered before the commencement of feeding and during every other
      term of feeding. Hierarchical linear random effects models and associated methods
      were used to examine the effects of treatment group on changes in cognitive
      performance over time. Analyses revealed that children receiving supplemental
      food with meat significantly outperformed all other children on the Raven's
      Progressive Matrices. Children supplemented with meat, and children supplemented
      with energy, outperformed children in the Control group on tests of arithmetic
      ability. There were no group differences on tests of verbal comprehension.
      Results suggest that supplementation with animal source food has positive effects
      on Kenyan children's cognitive performance. However, these effects are not
      equivalent across all domains of cognitive functioning, nor did different forms
      of animal source foods produce the same beneficial effects. Implications of these
      findings for supplementation programs in developing countries are discussed.

PMID- 14672298
TI  - Kenyan school children have multiple micronutrient deficiencies, but increased
      plasma vitamin B-12 is the only detectable micronutrient response to meat or milk
      supplementation.
AB  - Animal source foods (ASF) can provide micronutrients in greater amounts and more
      bioavailable forms compared to plant source foods, but their intake is low in
      many poor populations. However, the impact of ASF on micronutrient status of
      undernourished populations has not been assessed. Supplemental meat (60-85 g/d),
      milk (200-250 mL/d) or energy (isocaloric with the meat and milk, 240-300 kcal/d)
      were randomly assigned to 555 undernourished school children aged 5-14 y in a
      rural malaria-endemic area of Kenya, at one school meal daily for one school
      year. Blood and stool samples were collected at baseline and after 1 y to assess
      stool parasites, malaria, hemoglobin, serum or plasma C-reactive protein,
      ferritin, iron, zinc, copper, vitamin B-12, folate and retinol, and erythrocyte
      riboflavin. At baseline, there was a high prevalence of micronutrient
      deficiencies (iron, zinc, vitamins A and B-12 and riboflavin), yet plasma
      ferritin was low in few children, and none had low serum copper. At the end of
      the year of supplementation, plasma vitamin B-12 concentrations were
      significantly increased in children fed the Meat or Milk meal; prevalence of
      severe plus moderate deficiency fell from 80.7% at baseline to 64.1% in the Meat
      group and from 71.6 to 45.1% in the Milk group, respectively. No significant
      improvement was observed in the status of other micronutrients compared to the
      Energy and Control groups, although malaria and other infections may have
      obscured effects. Supplementation with small amounts of meat or milk reduced the
      high prevalence of vitamin B-12 deficiency in these children.

PMID- 14672299
TI  - Improving access to and consumption of animal source foods in rural households:
      the experiences of a women-focused goat development program in the highlands of
      Ethiopia.
AB  - Ethiopia is one of the poorest countries in Africa and its population experiences
      low and falling life expectancy rates, high infant, child and maternal mortality
      and high rates of child malnutrition. This is exacerbated by the fact that
      Ethiopia is not self-sufficient in animal products and is a net importer of food.
      For the majority of the population, most food energy (93%) is derived from
      vegetable products with 7% coming from animal source foods (ASF). FARM-Africa
      hypothesizes that the inadequate nutritional status of the population, which
      contributes to the high mortality rates in the country, is related to the
      population's low consumption of ASF, such as milk and meat. This article presents
      the findings of the Dairy Goat Project, the objectives of which included the
      improvement of family welfare through the generation of increased income and milk
      consumption. The project adopted an integrated approach and increased the
      productivity of local goats managed by women through a combination of better
      management techniques, genetic improvements and information exchange. Through pre
      and post-intervention analysis of data of those households within the project
      area, FARM-Africa demonstrated a considerable improvement in the nutritional
      status and family welfare of project participants. There was increased appearance
      of milk and meat products in local diets, and the addition of other foods, such
      as eggs and fresh vegetables, as a result of complementary activities established
      with funds generated through the principal activities of the Dairy Goat Project.

PMID- 14672300
TI  - Formative research to develop a nutrition education intervention to improve
      dietary iron intake among women and adolescent girls through community kitchens
      in Lima, Peru.
AB  - Formative research was conducted with 26 women and 16 adolescent girls to develop
      an education intervention through community kitchens (CK) in Lima, to increase
      their dietary iron intake and improve their iron status. A combination of
      qualitative research methods was used to explore perceptions about foods,
      nutrition, health, anemia and body image. The women recognized that there was a
      close association among eating well, "alimentarse bien", their health and
      prevention and treatment of anemia. They perceived that the nutritive value of a
      meal is determined primarily by its content of "nutritious" foods and by its
      being "balanced". Using this information the conceptual model of the education
      intervention was developed. The vulnerability of women to anemia was presented
      with the relationship between anemia and diet as the central focus. Feasible ways
      of achieving a nutritious diet were introduced to the community kitchens through
      promoting local heme iron sources and the consumption of beans with a vitamin C
      source. Animal source foods were amongst those considered to be nutritious and
      were "best buys" for iron content. CK searched for ways of assuring accessibility
      to these foods. The use of animal source foods in the community kitchen menus
      increased during the intervention.

PMID- 14672301
TI  - Experiences of a community-based dietary intervention to enhance micronutrient
      adequacy of diets low in animal source foods and high in phytate: a case study in
      rural Malawian children.
AB  - A community-based dietary diversification/modification intervention, employing a
      quasiexperimental design with a nonequivalent control group, was conducted in two
      intervention and two control villages in rural Southern Malawi. The aim was to
      enhance the content and bioavailability of micronutrients in maize-based diets of
      stunted children ages 30-90 mo. Efficacy was evaluated through a comparison of
      the changes in knowledge and practices, anthropometry, malaria screening,
      hemoglobin and hair zinc after 12 mo, common infections monthly postintervention
      and nutrient adequacy postintervention via 24-h recalls. Intervention diets were
      more diverse and of higher quality than the control diets, supplying
      significantly more animal source foods, especially soft-boned fish, but less
      phytic acid (p < 0.01). Median intakes of energy, protein, calcium, available
      zinc, heme iron and vitamin B-12 were greater (p < 0.05) in intervention compared
      to the control groups; some spread of knowledge and practices to the control
      groups occurred. Intervention enhanced Z-scores for mid-upper-arm circumference
      and arm muscle area (p < 0.001), but had no impact on weight or height gain.
      After controlling for baseline variables, mean hemoglobin was higher (107 vs. 102
      g/L; p < 0.01) postintervention, whereas incidence of anemia and common
      infections were lower in the intervention groups compared to the control groups,
      with no change in malaria or hair zinc status. Dietary strategies reduced the
      prevalence of inadequate intakes of protein, calcium, zinc and vitamin B-12, but
      not iron, because fish was the major source of animal food consumed. More efforts
      to raise small animals and promote their consumption are needed to enhance
      dietary quality and ensure optimal growth, health and cognitive development in
      young Malawian children.

PMID- 14672302
TI  - Experience with programs to increase animal source food intake in Thailand.
AB  - Thailand is a Southeast Asian country in rapid transition. It is considered to be
      food self-sufficient and an important food exporter in the world market.
      Quantitative data reveal that overall, the population of Thailand consumed a
      sufficient amount of most macronutrients and micronutrients, except for calcium.
      Nevertheless, there exist considerable problems of under- and overnutrition, due
      to unbalanced development in the past 40 y. Programs to increase animal source
      food intake in Thailand can be categorized into three main types: 1) programs to
      increase production; 2) programs to increase accessibility; and 3) programs to
      increase consumption. Overall production of fish, egg, chicken and pork has been
      adequate; and only beef and milk products need to be imported. To improve access
      for the poor, the National Poverty Alleviation Plan has been implemented since
      1981. In terms of consumption, the Royal Thai government has promoted overall
      nutritious diets, but does not have national programs to promote animal source
      foods specifically, except for milk. Programs to increase milk, fish and
      micronutrient consumption are highlighted. Also, some lessons learned and
      suggestions for future programs and research are discussed.

PMID- 14672303
TI  - Programs to improve production and consumption of animal source foods and
      malnutrition in Vietnam.
AB  - The objective of this paper is to review programs to improve production of animal
      source foods in Vietnam, emphasizing the VAC ecosystem and trends in
      undernutrition during past decades. The food consumption surveys of the
      Vietnamese population in 1985 showed that food intake was inadequate, especially
      animal protein. Most protein came from rice; the consumption of meats, beans and
      fish was negligible. During the last 10 y, much attention was paid to improving
      the health and nutritional status of the Vietnamese people. Many programs were
      implemented in Vietnam to improve the food intake and nutritional status of the
      people, and especially the intake of animal source foods. The VAC system is a
      traditional type of farming for Vietnamese people. The aim of VAC is to provide
      diversified agricultural products to meet the complex nutritional demands of man.
      Based on the scientific fundamentals of VAC, many different models of VAC have
      been developed at a national level. The intervention programs to improve
      production and consumption of animal source foods, and the VAC ecosystem in
      Vietnam during the last decade have been successful. The population's dietary
      intakes have clearly improved in terms of both quality and quantity. The
      consumption of staple foods in 2000, including meats, fish, fats and oils, and
      ripe fruits was much higher compared to 1987. The prevalence of undernutrition in
      children <5 y old, and of chronic energy deficiency (CED) in women of
      reproductive age, has been remarkably reduced.

PMID- 14672304
TI  - The effect of micronutrient deficiencies on child growth: a review of results
      from community-based supplementation trials.
AB  - Several micronutrients are required for adequate growth among children. However,
      it has been unclear as to which nutrient deficiencies contribute most often to
      growth faltering in populations at risk for poor nutrition and poor growth.
      Therefore, evidence from community-based, randomized, placebo-controlled,
      micronutrient supplementation trials was reviewed to determine which
      micronutrient deficiencies have been found to be causal to growth faltering.
      Although correction of growth-limiting nutrient deficiencies may be achieved
      through provision of pharmacological nutrient supplements, it also was of
      interest to review evidence for the use of animal source food supplements to
      improved growth among children in at-risk populations. There is strong evidence
      for the contribution of zinc deficiency to growth faltering among children; even
      mild to moderate zinc deficiency may affect growth. Vitamin A and iron
      deficiencies also have been demonstrated to cause growth faltering, however only
      when the deficiency state of these nutrients is severe. Several controlled,
      community-based intervention trials that have included animal source foods,
      either together with additional micronutrient supplements or with other
      supplemental food sources, have demonstrated positive growth responses among
      children. Three trials that used an animal source food alone (skim milk powder)
      also resulted in a positive growth response. However, the geographic scope of the
      latter three trials was limited, and it remains unclear to what extent
      supplemental animal source foods alone and which types of animal source foods can
      be used to improve growth among children in at-risk populations.

PMID- 14672305
TI  - Small indigenous fish species in bangladesh: contribution to vitamin A, calcium
      and iron intakes.
AB  - Fish play an important role in the Bangladeshi diet, constituting the main and
      often irreplaceable animal source food in poor rural households. Fish consumption
      is dominated by wild small (length <25 cm) indigenous fish species (SIS). The
      vitamin A content in SIS varies, from <100 microg of retinol equivalents (RE)/100
      g raw edible parts, to >2,500 microg RE/100 g raw edible parts in mola
      (Amblypharyngodon mola). The study addressed the dietary contribution of fish to
      vitamin A, calcium and iron intakes and the potential of integrating SIS,
      including mola, into existing carp polyculture ponds. Fish consumption (wild and
      cultured fish) was surveyed by 5-d recall interviews in 84 poor rural households
      in Kishoreganj district in 1997-1998. Fifty-nine of the households cultured carp
      and SIS in small (mean size 400 m2) domestic ponds. Total household fish
      consumption was unaffected by the domestic aquaculture production. SIS from wild
      sources contributed 84% of the total fish consumption. In the peak season
      (October), SIS contributed 40% (median 23%) of the recommended vitamin A intake
      at the household level (n = 84). Thirty-four households cultured mola along with
      carp. Cultured mola used for household consumption contributed 20% (median 18%)
      of the recommended intake of vitamin A at the household level. Wild SIS is an
      important source of vitamin A and calcium in Bangladesh. Mola can be integrated
      in existing carp culture without negative effects and can contribute to increased
      vitamin A intake in rural households.

PMID- 14672306
TI  - The impact of semi-scavenging poultry production on the consumption of animal
      source foods by women and girls in Bangladesh.
AB  - Semi-scavenging poultry production is a potential avenue for increasing poultry
      production and income, and improving the livelihoods of members of poor rural
      households. Since 1998, the Participatory Livestock Development Project (PLDP)
      has used this strategy to increase poultry production and household income in the
      northwest and north-central regions of Bangladesh. The aim of this study was to
      investigate the impact of the PLDP on the food and nutrient intakes of females in
      the PLDP-adopting households. A cross-sectional comparative study was conducted
      using data for 35 women of reproductive age and 35 girls (5-12 y old) from both
      the PLDP-adopting and nonadopting households. Data was collected in 1999 on food
      consumption as well as poultry production, household socioeconomic status and
      food preferences, using quantitative and qualitative questionnaires. High
      yielding parent poultry stock and egg production were significantly higher in the
      PLDP households (P < 0.001). Intakes of chicken and eggs were similar in both
      groups and negligible compared to other foods, especially rice, vegetables and
      fish. Fish intake was higher in the PLDP-adopting women (P < 0.08) and girls (P <
      0.06) compared to their nonadopting counterparts. Women had a higher preference
      for small fish compared to other animal foods. The results of this study
      suggested that if a project such as the PLDP, which increases animal food
      production and income in rural Bangladesh, also aims to increase intakes of
      animal source foods in females, then the accessibility of small fish must be
      ensured.

PMID- 14672307
TI  - Applying a nutribusiness approach to increase animal source food consumption in
      local communities.
AB  - Animal source foods (ASF) in the diets of schoolchildren are beneficial for
      supporting optimal physical and cognitive development. Nevertheless, behavioral
      change and economic development are needed to increase and sustain adequate meat
      product consumption by schoolchildren in developing countries. A NutriBusiness
      enterprise may be one way for local communities to promote economic development
      while increasing the availability of meat for children. This work evaluates the
      feasibility of a NutriBusiness enterprise involving the production of rabbits and
      the manufacture of solar dried snack food. Some rabbits would be kept for home
      use, whereas others would be used in the manufacture of a rabbit-sweet potato
      dried snack food that could be fed to children or sold for income. The
      NutriBusiness enterprise would be composed of participants from the community
      contributing to a cooperative effort for setting up a manufacturing facility and
      organizing production, manufacturing and marketing functions. A unit operation
      for rabbit-sweet potato Chiparoos, based on full-capacity operation of a single
      solar drier would involve up to 110 shareholder families, each producing 240
      rabbits/y with 120 used at home and 120 sold for Chiparoos manufacture.
      Participation in the enterprise would increase the availability to children of
      iron, zinc and vitamin B-12, and other nutrients, and provide approximately 350
      dollars/y additional income for the family.

PMID- 14672308
TI  - Sociocultural and household factors impacting on the selection, allocation and
      consumption of animal source foods: current knowledge and application.
AB  - This paper reviews the literature on cultural and household level constraints on
      the consumption of animal source foods (ASF). Food proscriptions do not appear to
      significantly limit food consumption in the areas where this question has been
      examined, with the possible exception of adult women in some settings.
      Preferential food allocation patterns, based on economic contribution, social
      valuation and other factors do play a role in limiting the intake of animal
      source foods for children and women in some settings. Economic factors limit
      access to ASF at the household level. Child care patterns in different cultural
      settings can also serve to enhance or limit the consumption of ASF. Social
      marketing and positive deviance approaches have had some success in increasing
      the intake of ASF by using formative research and participatory approaches. The
      paper concludes with a series of research questions for further investigation.

PMID- 14672309
TI  - Solutions exist for constraints to household production and retention of animal
      food products.
AB  - This article reviews constraints to household level animal source food production
      in developing countries and suggests solutions to some of these constraints.
      These constraints include land, labor, money, feed quality, water, disease,
      animal genetics, roles for animals beyond food production, grazing techniques and
      an understanding of the entire agricultural system at the household level. Better
      understanding of farming systems and the elements that comprise it which affect
      animal food production permits wise management of nutrient flows and enhanced
      sustainability.

PMID- 14672310
TI  - Global production and consumption of animal source foods.
AB  - This article provides interpreted statistics and information on global livestock
      production and the consumption of animal source foods from the Food and
      Agriculture Organization of the United Nations statistical data base. Country
      data are collected through questionnaires sent annually to member countries,
      magnetic tapes, diskettes, computer transfers, websites of the countries,
      national/international publications, country visits made by the FAO statisticians
      and reports of FAO representatives in member countries. These data show that
      livestock production is growing rapidly, which is interpreted to be the result of
      the increasing demand for animal products. Although there is a great rise in
      global livestock production, the pattern of consumption is very uneven. The
      countries that consume the least amount of meat are in Africa and South Asia. The
      main determinant of per capita meat consumption appears to be wealth. Overall,
      there has been a rise in the production of livestock products and this is
      expected to continue in the future. This is particularly the case in developing
      countries. The greatest increase is in the production of poultry and pigs, as
      well as eggs and milk. However, this overall increase obscures the fact that the
      increased supply is restricted to certain countries and regions, and is not
      occurring in the poorer African countries. Consumption of ASF is declining in
      these countries, from an already low level, as population increases.

PMID- 14672311
TI  - Economic constraints on production and consumption of animal source foods for
      nutrition in developing countries.
AB  - Livestock ownership currently supports and sustains the livelihoods of an
      estimated 675 million rural poor, who depend partially or fully on livestock for
      their income and/or subsistence. Human population growth, increasing urbanization
      and rising incomes are predicted to double the demand for, and production of,
      livestock and livestock products in the developing countries over the next 20 y.
      Land availability limits the expansion of livestock numbers in extensive
      production systems in most regions, and the bulk of the increase in livestock
      production will come from increased productivity through intensification and a
      wider adoption of existing and new production and marketing technologies. The
      significant changes in the global consumption and demand for animal source foods,
      along with increasing pressures on resources, are having some important
      implications for the principal production systems. Production at the smallholder
      level is constrained by a number of barriers, lack of competitiveness and risk
      factors. The future holds both opportunities as well as serious pitfalls for
      animal production in developing countries. There is a danger that livestock
      production and processing will become dominated by integrated large-scale
      commercial operations, displacing small-scale livestock farmers and thus
      exacerbating rural poverty and malnutrition. Conversely, correctly managed, a
      dynamic livestock sector could prove to be a catalyst for stimulating rural
      economies. However, the livestock sector will not take on this role on its own,
      but requires proactive policies on behalf of the private and public sectors.

PMID- 14672312
TI  - Photolysis and biodegradation of selected resin acids in River Saale water,
      Germany.
AB  - The River Saale is the Elbe's major tributary flowing through the state of
      Thuringia, Germany and receives organics inputs from several industrial
      facilities including pulp and paper mills. Resin acids constitute a major class
      of polar organics and environmental toxins derived primarily from pulp and paper
      processing of softwoods. Since wastewater treatment methods at pulp and paper
      mills are not always capable of removing the persistent resin acids prior to
      effluent discharge, alternative or complementary degradation methods may be
      required. Here, the facile photodegradation of four resin acids--abietic,
      dehydroabietic, isopimaric, and pimaric--was observed with pseudo-first-order
      kinetics when exposed to broad band and UV254-radiation. Further experimentation
      in rotating annular biofilm reactors with UV-exposed and unexposed River Saale
      water spiked with abietic and dehydroabietic acids indicated that photolysis is
      an effective pretreatment method for resin acid biodegradation. The bacterial
      toxicity of the aqueous resin acids solutions as measured with Microtox
      luminescence assays decreased with exposure time. Consequently, photo- and
      biodegradation of the resin acids did not generate any notable amounts of toxic
      intermediates and/or the intermediates formed were further degraded into
      compounds of lower toxicity than the parents. With tandem photo- and biological
      treatment at pulp and paper mills, as well as in-situ degradation by solar
      radiation and natural biofilms within the River Saale, resin acid inputs can be
      reduced in both concentration and toxicity to near undetectable levels with
      little or no ecological significance.

PMID- 14672313
TI  - Bacterial adsorption and transport in saturated soil columns.
AB  - Microbial activities directly affect the environmental quality of water, soil,
      and sediments. To improve our understanding of microbial attachment and transport
      in the subsurface, experimental studies were performed to evaluate bacterial
      adsorption and transport in two types of soil, Smolan (27% clay) and Haynie (5.5%
      clay) soils. Results indicate that bacterial breakthrough was slightly faster in
      columns with lower clay content and that the most rapid rate of bacterial
      adsorption occurred during the first 60 min of exposure.

PMID- 14672314
TI  - An environmental assessment of mold concentrations and potential mycotoxin
      exposures in the greater Southeast Texas area.
AB  - An assessment of indoor air quality in homes from the greater Houston and
      Southeast Texas area was sampled over a three-month period to ascertain the
      potential toxic exposure to molds and mycotoxins. In 2001 Houston experienced
      widespread flooding due to Tropical Storm Allison. The slow receding waters
      allowed molds to proliferate to great levels and affected many homes and
      businesses in and around the Houston area. Source (air) and surface (swab, tape,
      and bulk) samples were taken in fungal contaminated residences to measure the
      amounts of airborne and surface contaminants. Indoor airborne counts of fungal
      spores that were identified to be 80% or more of the outside counts of similar
      fungal genera were classified as indoor air contaminants. This study identified
      species of Aspergillus, Penicilliulm, and Cladosporium at levels ranging from 80%
      to 20 times greater than the corresponding outdoor readings in the greater
      Southeast Texas area. Aspergillus and Penicillium species are considered
      potentially toxic to humans at elevated levels due to their ability to produce
      mycotoxins. Cladosporium is considered nonpathogenic, but can still cause
      allergenic reactions from hyphal fragments. Surface sampling which is utilized
      for identification of visible mold contaminants, identified species of
      Aspergillus. Penicillium, Chaetomium, Cladosporium, and Stachybotrys ranging from
      1 to 100 total colony counts (1-100% for tape and bulk noncultured assays)
      contingent upon the extent of visual contamination. The numerical values from
      surface sampling were used primarily to identify the degree of visual
      contamination, as well as, identify any molds that may have been too heavy to
      become aerosolized.

PMID- 14672315
TI  - Arsenic uptake by native fern species in Thailand: effect of chelating agents on
      hyperaccumulation of arsenic by Pityrogramma calomelanos.
AB  - Nineteen native fern species collected from an area in Thailand with high arsenic
      concentration in soil and in ground water as a result of tin mining was screened
      for elevated arsenic concentration in fronds. Two species of fern were found to
      contain elevated arsenic in their fronds in nature: Pityrogramma calomelanos (108
      1156 microg g(-1) dried weight) and Pteris vittata (79 microg g(-1) dried
      weight). Under hydroponic culture Pityrogramma calomelanos (a silver back fern)
      accumulated arsenic in its shoot at rate of 4616 microg(-1) (dried weight). The
      accumulation of arsenic in Pityrogramma calomelanos shoot doubled with the
      addition of an EDTA (Ethelenediamine tetraacetic acid) chelating agent. The
      highest accumulation occurred 6 weeks after exposure to 10 mg L(-1) arsenic as
      disodium hydrogen arsenate. The addition of another chelating agent, DMS
      (Dimercaptosuccinic acid), resulted in a 5-fold decrease in arsenic concentration
      in the Pityrogramma calomelanos shoot compared to control after 6 weeks of
      exposure to arsenic. The contrasting effect of the EDTA and DMSA chelating agent
      was attributed to the strong binding of the thiol group to arsenic ion. This
      study indicated that Pityrogramma calomelanos uptake and translocate arsenic in
      the form of arsenate and arsenite rather than the As-DMSA complex. Using
      phytoextraction efficiency calculations, it was determined that Pityrogramma
      calomelanos gave the highest arsenic phytoextraction efficiency at 6 weeks after
      exposure to arsenic in the EDTA treatment, with an efficiency of 77.8 mg As based
      on whole plant biomass.

PMID- 14672316
TI  - Lead contamination of soils in Belize City, Belize, Central America.
AB  - In order to assess the amount and distribution of lead pollution in soils in
      Belize City, Belize, seventy-five samples were collected from three distinct
      areas around the city (roadsides, houses, and playgrounds and schools). This
      study has provided data to establish the first soil lead database for Belize
      City, Belize. The soil samples generally exhibited pH values above 7, less than
      18% organic matter, and more than 50% sand was found in 92% of the samples. These
      physical and chemical characteristics prevent the lead from accumulating in the
      upper layers of soil. However, high or hazardous levels were found in all sample
      categories. In the schoolyards and playgrounds category. the levels range from 3
      ppm to 780 ppm, and average 131 ppm. The roadside samples had a range of 3 ppm to
      5450 ppm, and average 445 ppm. The housing samples had the highest
      concentrations, with the range from 9 ppm to 104, 500 ppm and an average of 638
      ppm. The geographic distribution of lead within the city appears to be somewhat
      random, although the most contaminated areas are generally in the south part of
      the city. The distance to potential source of contamination, for example peeling
      paint or a road, affects lead concentration, as does percent of organic matter in
      the soil. The physical characteristics that normally aid in the retention of lead
      in soil are not generally present in Belize City; however, the lead levels are
      dangerously high.

PMID- 14672317
TI  - Estimation of cytotoxicity to HEP-G2 cells of 255 environmental pollutants and
      water using QSAR (Quantitative Structure-Activity Relationship).
AB  - Although bioassays are considered to be a rational method for environmental
      management, the procedure is generally too complicated to be applied to daily
      water quality management. In this study, the feasibility of using for application
      of a conventional QSAR (Quantitative Structure-Activity Relationship) method was
      examined to estimate the cytotoxicity of various pollutants found in
      environmental water. logP, pKa, and molecular weight were chosen as the
      physico/chemical properties of the pollutants, and defined equations for
      estimating cytotoxicity based on multiple linear regression analysis between
      these properties and in vitro cytotoxicity data from our previous results. As a
      result, a method for estimating cytotoxicity of environmental pollutants that had
      a certain probability (R>0.8) for the 255 chemicals was successfully developed.
      Considerably high reliability was shown in the leave-one-out prediction of multi
      regression analysis. In addition, the cytotoxicity of environmental water samples
      was estimated based on multi-regression analysis, using as our samples leachates
      from 25 landfill sites in Japan. The method developed in this study estimated
      quantitatively the cytotoxicity of the environmental water from chemical analysis
      data without conducting a cytotoxicity test.

PMID- 14672318
TI  - Theoretical analysis of the influence of process parameters on the use of an
      encapsulated phosphate buffer to control pH in a soil column.
AB  - A one-dimensional mathematical model was developed to analyze the influence of
      different physical and chemical parameters on the performance of an encapsulated
      phosphate buffer for controlling pH and enhancing a pH-dependent process in a
      soil column. Three scenarios were investigated where base equivalents are
      produced through the degradation of the target compound (scenario I), through
      reactions in the matrix (scenario II), and a combination of both mechanisms
      (scenario III). In all three scenarios, the production of base equivalents is
      countered by the release of the acidic core of the encapsulated phosphate,
      resulting in an enhanced removal of the target compound. A sensitivity analysis
      on the model shows that under the conditions investigated, the removal of the
      target compound is dependent on the flowrate, porosity, dispersion coefficient,
      reaction rate constants, mass of added capsules, and the point of addition of the
      capsules. The approach can be used to analyze scenarios where encapsulated
      buffers can control pH and optimize pH-dependent processes in a soil column.

PMID- 14672319
TI  - Assessment of heavy metal contamination of seawater and marine limpet, Patella
      vulgata L., from Northwest Spain.
AB  - In the present work, both seawater and limpets (Patella vulgata L.) were
      collected from different sampling points in the Vigo estuary area (Galicia, NW
      Spain) and their heavy metal concentrations (Zn, Cd, Pb, Cu) were determined by
      means of a voltammetric technique. The results showed a direct relationship
      between the heavy metal levels in seawater and the content in biological samples,
      especially those obtained from limpet soft tissues, directly related to the
      increasing importance of anthropogenic environmental contamination. Heavy metal
      concentrations were usually higher in soft tissues than in shell, with a maximum
      difference corresponding to Cd and Zn (average of 93.6 and 86 folds,
      respectively). As expected, heavy metal content was higher in animal samples
      situated in inner part of the estuary zone, except for cadmium content in soft
      tissues, where a maximum of 5.62 ppm was quantified in limpet soft tissues
      collected next to the open sea area. Statistical analysis allowed the
      establishment of a clear relationship between Zn and Cd content in both shells
      and soft tissues from limpet, and especially between Zn and Cu in soft tissues (p
      < 0.001).

PMID- 14672320
TI  - Variation of microcystins in a lake for water supply.
AB  - A site investigation was conducted to correlate the relationships between
      microcystins (MC) concentration and algal growth in Dianchi Lake in China.
      Laboratory experiments were undertaken to test the effects of sediment
      adsorption, photoirradiation and biodegradation on microcystins removal.
      Bioaccumulation of microcystins was also determined using silver carp fish. It
      was observed that MC concentrations varied in accordance with algae growth in
      Dianchi Lake. The results obtained in the laboratory demonstrated that the
      removal of MC with fresh sediments was less than 10%, photoirradiation removed
      more than 75% MC within two hours, and the biodegradation needed much longer time
      to produce substantial degradation of MC. The results suggest that
      bioaccumulation of microcystins in fish was not significant in Dianchi Lake.

PMID- 14672321
TI  - Fluctuation of microcystins in water plant.
AB  - This study was undertaken to investigate the distribution and variation of
      microcystins (MC) from a water resource to a water plant in China including long
      distance transportation, ClO2 preoxidation, coagulation/precipitation,
      filtration, and disinfection. Advanced treatment methods including ozonation and
      granular activated carbon (GAC) adsorption were tested to remove microcystins
      from drinking water. The results indicated that, when containing high level of
      algae in raw water, preoxidation at 2 mg/L of ClO2 was not enough to stop algae
      growth in long distance transportation. In the water plant studied, both
      coagulation and filtration caused significant increase instead of removal of
      microcystins in drinking water. Chlorine disinfection removed part of
      microcystins. However, both ozonation and GAC adsorption were able to remove
      microcystins completely, thereby improving the quality of drinking water in terms
      of microcystins.

PMID- 14672322
TI  - A long-term study of oxides of nitrogen, sulphur dioxide, and ammonia for a port
      and harbor region in India.
AB  - A long-term study of oxides of nitrogen (NOx), sulphur dioxide (SO2), and ammonia
      (NH3) has been performed in a port and harbor region in India from January 1997
      to December 2000. Meteorological data was also collected to establish the
      correlation with gaseous pollutants concentrations. Monthly mean concentrations
      of NOx were in the range of 19.5-59.0 microg/m3 and were observed to be highest
      during winter season. Monthly mean concentrations of SO2 were in the range of 8.6
      51.3 microg/m3 and were observed to be highest during winter season. The
      concentrations of SO2 increased gradually from 18.8 microg/m3 in 1997 to 33.3
      microg/m3 in 2000. This may be attributed to the increase in port activities and
      ship traffic, which had an annual growth of about 15%. Monthly mean
      concentrations of NH3 were in the range of 87.1-235.1 microg/m3 and the maximum
      concentration was observed during post-monsoon season. It may be concluded that
      NOx and SO2 have their maximum values during winter season while NH3 has a
      maximum value during post-monsoon season. Statistical analysis was carried out
      for air pollutant data for the period 1997-2000 and correlation between gaseous
      pollutants (NOx, SO2, NH3) and meteorological parameters (temperature and wind
      speed) was estimated. NH3 was found to be weakly correlated with NOx (0.46),
      strongly correlated with SO2 (0.75) and negatively correlated with wind speed (
      0.60). The highest correlation (0.87) was observed between SO2 and NOx because of
      common sources. A strong negative correlation was found between wind speed and
      gaseous pollutants. The above finding is also supported by monitoring results
      that when the wind velocity doubled, the concentrations of pollutants decreased
      sharply to about a half. Regression analysis showed that relationship among NOx,
      SO2, wind speed, and temperature was moderate to strong while that among NH3,
      wind speed, and temperature was poor. Hence regression equations could be
      developed for predicting NOx and SO2 concentrations.

PMID- 14672323
TI  - Disinfection of hospital wastewater by continuous ozonization.
AB  - The disinfection of hospital wastewaters using the ozonization process was
      studied. The concentrations of ozone required to reach a sudden drop of coliform
      and Pseudomonas aeruginosa in the wastewater are 4.0-7.0 and 3.0-5.0 mg L(-1),
      respectively. For the hospital wastewater, the disinfection efficiencies were
      0.518S(-1.1) for coliforms, 0.509S(-1.06) for Pseudomonas aeruginosa and 0.254S
      (1.54) for total count, respectively. As to the effects of ozone input methods on
      the disinfection efficiency, the continuous ozonization process was ten times
      higher than the batch input process. The low COD removal rate was obtained at
      25.0 mgL(-1) of ozone concentration for hospital wastewater. However, more
      biodegradable compounds resulted in the treated mixture.

PMID- 14672324
TI  - Work exposure to urban pollutants and urinary homovanillic acid.
AB  - The aim of this study was to evaluate whether traffic policemen exposed to urban
      pollutants could be at risk of alterations on urinary homovanillic acid in 24h
      HVA(U) excretion levels, an end product of dopamine catabolism, compared with a
      control group. Traffic policemen were matched by sex, age, and working life with
      control group after excluding principal confounding factors; 50 traffic policemen
      (29 men and 21 women) with outdoor activity exposed to urban pollutants and 50
      not exposed subjects (29 men and 21 women) with indoor activity were included in
      the study. The HVA(U) excretion levels were significantly higher in male and
      female traffic policemen compared to not exposed subjects (respectively P=0.003;
      P=0.023). The authors hypothesize an effect on the excretion of HVA(U) in traffic
      policemen exposed to chemical and physical stressors, according to HVA(U)
      modifications found by other authors in workers exposed in factories.

PMID- 14672325
TI  - Evaluation of disinfection by-products formation during ozonation of bromide
      containing groundwater.
AB  - Ozonation of natural waters containing bromide ion leads to the formation of
      inorganic bromate and many organic by-products, only a few of which have been
      identified. The object of this article is to identify primary ozone disinfection
      by-products (DBPs) and to ascertain the effects of bromide (Br-) concentration,
      pH, natural organic material (NOM) characteristics, ozone dosage, and other water
      quality parameters on their formation in ozonated waters derive from seven
      groundwaters. The results of this study show that bromate formation is favored at
      high pH, high initial bromide concentrations, and high ozone dosage, but low
      dissolved organic carbon (DOC), and ammonia levels. On the other hand, organic by
      products were favored at low pH, high bromide levels, and high O3/DOC ratios. In
      general, bromoform (CHBr3) and aldehydes concentration first increased, then
      diminished, as the dosage of ozone was increased. Ammonia appears to reduce both
      bromate and bromoform. Additional brominated organic by-products produced via
      ozonation of a variety of groundwaters in this study were monobromoacetic acid
      (MBAA), dibromoacetic acid (DBAA), 2,4-dibromophenol (2,4-DBP),
      dibromoacetonitrile (DBAN). The levels of these by-products are affected by the
      water quality characteristics. The background organic nitrogen (organic-N)
      content of the different water sources may be correlated with amounts of DBAN
      formed. It was also found that the characteristic of organic precursors have
      significant influences on brominated organic by-products formation. Humic acid
      demonstrated the highest CHBr3, DBAA, and 2,4-DBP formation, whereas hydrophilic
      neutral produced less CHBr3 and 2,4-DBP than the rest of the organic fractions
      but produced the highest amount of DBAN.

PMID- 14672326
TI  - Using oxidation-reduction potential (ORP) and pH value for process control of
      shortcut nitrification-denitrification.
AB  - A new low cost technology for simultaneous carbon-nitrogen removal from soybean
      wastewater has been developed in this study. The technology is performed through
      shortcut nitrification-denitrification. The process operated under realtime
      control of aeration and mixing time. The shortcut nitrification-denitrification
      in sequencing batch reactor (SBR) was achieved efficiently and steadily by
      controlling temperature (28 +/- 0.5 degrees C) and using real-time control
      strategies. This enabled the prevention of nitrite oxidation, leading to lower
      operational costs. The feasibility of oxidation-reduction potential (ORP) and pH
      value as control parameter for shortcut nitrification-denitrification process was
      also investigated. Results showed that the average removal efficiency of ammonium
      was more than 95%, and nitrosation rate (NO2(-)-N/NOx(-)-N) was reached to 96%.
      At the same time, the variation of oxidation--reduction potential (ORP) and pH
      value was well related to organic matter degradation and ammonium oxidation in
      SBR. So that judgment on the ending of nitrification and denitrification can be
      based on the inflection point on the varied curve of ORP and pH throughout each
      SBR processing cycle, and thus reducing aeration and mixing time for saving
      energy source. The method saves organic energy up to 40% of chemical oxygen
      demand (COD) in denitrification process, which should reduce the need for an
      extra external source of organic carbon. Shorter hydraulic retention time should
      allow the volume of the reactors to diminish, and thus diminish investment costs.
      Lower oxygen demand of about 25% gives lower exploitation costs.

PMID- 14672327
TI  - Emission of burning emulsified diesel oil with sodium sulfate in salty
      atmospheric air.
AB  - The effects of sodium sulfate in fuel oil and salty atmospheric air on the
      emission characteristics of furnaces or boilers burned with emulsified diesel
      oils are considered in this study. An industrial cylindrical furnace made of
      stainless steel associated with an automatic oil-fired burner was used for the
      emission measurements. Both neat diesel oil and emulsified diesel oil with
      distilled water were used as the tested oils. A homogenizing and emulsifying
      machine was employed to stir the diesel oil and sodium sulfate powder into a
      homogeneous oil mixture, and to prepare emulsions of micro-droplets of water
      dispersed in diesel oil. The experimental results showed that the existence of
      sodium chloride in atmospheric air enhanced SO2 formation. The use of emulsified
      diesel oil with 300-ppm sodium sulfate as fuel reduced the burning gas
      temperature and NOx emission while increased O2 emission. Moreover, the presence
      of sodium chloride in atmospheric air hindered the completeness of the combustion
      process and thus resulted in lower burning efficiency and larger excess oxygen
      emission.

PMID- 14672328
TI  - Simultaneous removal of volatile organic compounds (VOCs) and nitrogen: batch
      test.
AB  - A batch test was conducted to investigate the effect of the chemical oxygen
      demand, (COD)/N ratio, nitrate, nitrite and temperature, on the microbial
      degradation of volatile organic compounds (VOCs), and the denitrification
      capability using VOCs-acclimatized and un-acclimatized cultures. The nitrite
      reduction rates differed with each reactor, as follows: 15.418 NO2-N mg MLVSS g(
      1) h(-1) in the benzene and methanol (BM) reactor, 27.463 NO2-N mg MLVSS g(-1) h(
      1) in the toluene and methanol (TM) reactor and 44.358 NO2-N mg MLVSS g(-1) h(-1)
      in the methanol (M) reactor. According to the COD/N ratio, the nitrate reduction
      rates of the BM and TM reactors acclimatized by VOCs changed in the ranges of
      29.4-33.41 NO3-N mg MLVSS g(-1) day(-1) and 56.4-65.9 NO3-N mg MLVSS g(-1) day(
      1), respectively. Thus, benzene was not effectively utilized as a carbon source.
      Conversely, toluene was utilized as a carbon source by the denitrifiers under
      substrate limited conditions. The specific denitrification rates were also
      greater in the TM reactor than those for both the substrate limited and unlimited
      conditions in the BM reactor.

PMID- 14672329
TI  - Effects of fibronectin, VEGF and angiostatin on the expression of MMPs through
      different signaling pathways in the JEG-3 cells.
AB  - PROBLEM: The objective of this study was to evaluate the possible signal pathway
      of fibronectin (FN), vascular endothelial growth factor (VEGF) and angiostatin
      (AS) on the expression of matrix metalloproteinases (MMPs) in JEG-3 cells.
      METHODS OF STUDY: JEG-3 cells were cultured and were examined for the effect of
      FN, VEGF and AS on the expression of MMPs by immunocytochemistry, gelatin
      zymography, Western blot analysis and reverse transcription-polymerase chain
      reaction (RT-PCR). RESULTS: We found that up-regulation of the expression of MMPs
      was induced by FN and VEGF through the focal adhesion kinase (FAK)/mitogen
      activated protein kinase (MAPK) and Flt-1/p38SAPK/MAPKAPK2 signaling pathways,
      respectively. Furthermore, AS down-regulated the expression of MMPs through the
      integrin alphaVbeta3/FAK signaling pathway independent of the integrin-binding
      motif Arg-Gly-Asp (RGD). CONCLUSION: These data indicate that the expression of
      MMPs is regulated by many independent factors (such as FN, VEGF and AS) through
      different signaling pathways which influence the behavior of trophoblast cells.

PMID- 14672330
TI  - Upregulation of interleukin-8 by hypoxia in human ovaries.
AB  - PROBLEM: To evaluate the effect of hypoxia on interleukin (IL)-8 expression in
      human ovarian follicles. METHOD OF STUDY: Follicular fluid (FF) from each
      follicle was separately collected from women undergoing in vitro fertilization
      and embryo transfer. Concentrations of oxygen, progesterone, estradiol, IL
      1alpha/beta, IL-8, and tumor necrosis factor (TNF)-alpha in FF were measured.
      Isolated granulosa-lutein cells (GLC) from obtained FF were cultured under
      normoxic or hypoxic conditions, and concentrations of IL-8 in culture media were
      measured. RESULTS: Simple regression analysis demonstrated a significant negative
      correlation between the concentrations of IL-8 and oxygen in FF (r = 0.50, P <
      0.0001). However, none of the concentrations of progesterone, estradiol, IL
      1beta, and TNF-alpha in FF showed a significant correlation with IL-8
      concentrations. Hypoxia stimulated the secretion of IL-8 by cultured GLC over
      twofolds compared with a normoxic control (P < 0.05). CONCLUSIONS: These findings
      suggest that IL-8, like other angiogenic factors, is upregulated under hypoxic
      condition, which argues that hypoxia in the ovarian follicles comes into play in
      ovarian functions by inducing a range of proangiogenic and chemoattractive
      substances.

PMID- 14672331
TI  - Predominant intracellular expression of CXCR4 and CCR5 in purified primary
      trophoblast cells from first trimester and term human placentae.
AB  - PROBLEM: The aim of the present study was to define the expression of CXCR4 and
      CCR5 on non-cultured non-stimulated primary human trophoblast cells (TCs)
      immediately after their immunopurification. METHOD OF STUDY: We have evaluated by
      flow cytometric analysis and immunofluorescence, highly purified primary TCs
      prepared from first trimester (8.2 +/- 0.3 weeks, n = 15) and term (Caesarean
      section, n = 10) placentae for the cell surface and intracellular expression of
      CXCR4 and CCR5. RESULTS: There was a high level of individual variability for
      CXCR4 and CCR5 expression between trophoblast batches. In first trimester and
      term placentae TCs, we found a greater number of TCs preparations expressing
      intracellular CXCR4 than CCR5 (P < 0.05). Both receptors were predominantly
      localized in the intracellular compartment of TCs, whatever if isolated from
      first trimester or term placentae. CONCLUSIONS: The functional consequences of
      the predominance of CXCR4 expression and of cellular addressing are briefly
      discussed.

PMID- 14672332
TI  - Maternal serum levels of pro-inflammatory cytokines in missed and threatened
      abortion.
AB  - PROBLEM: A study of association between pro-inflammatory cytokines, and missed
      and threatened abortions with good outcome has been performed. METHOD OF STUDY:
      The presence of pro-inflammatory cytokines, namely interleukin (IL)-8 and IL-12
      and the soluble interleukin-2 receptor (SIL-2R) was investigated in maternal
      serum of 12 patients with threatened abortion twice (at admission and discharge),
      14 patients with missed abortion, 14 women with healthy first-trimester
      pregnancy, and 14 normal non-pregnant women, using specific enzyme-linked
      immunosorbent assays. RESULTS: SIL-2R and, in particular, IL-12 was detected with
      significantly higher levels in missed abortion group compared with all other
      groups. IL-8 was detected with no significant difference among all the groups
      studied. CONCLUSIONS: In spite of caution due to the small sizes of the subject
      samples, these results support a role of the immune system in the first trimester
      pregnancy and hypothesize that missed abortion may be associated with an enhanced
      Th1 reactivity, whereas threatened abortion with good outcome resembles the
      normal pregnancy with a non-enhanced Th1 reactivity.

PMID- 14672333
TI  - Comparative effects of L-tryptophan and 1-methyl-tryptophan on immunoregulation
      induced by sperm, human pre-implantation embryo and trophoblast supernatants.
AB  - PROBLEM: The hypothesis that indoleamine 2,3-dioxygenase (IDO) is necessary to
      regulate lymphocyte functions at the feto-maternal interface has been postulated,
      although a possible role of tryptophan (Trp) depletion in the T-cell tolerance
      during insemination as well as implantation has not been previously investigated.
      METHOD OF STUDY: Allogeneic phytohaemagglutinin stimulated lymphocytes were
      supplemented with pre-implantation embryo supernatant (PES), seminal plasma (SP),
      spermatozoa culture supernatant (SCS), spermatozoa, trophoblast cells, or
      placenta explant culture supernatants, and analyzed for expression of CD25, CD71,
      and CD69. Trp-degrading activity was assessed by addition of 1-methyl-Tryptophan
      or L-Trp. RESULTS: PES, SP, trophoblast, and explant supernatants reduced the
      expression of CD25 in CD3 lymphocytes. Inhibition of IDO as well as Trp
      supplementation prevented these effects. CONCLUSIONS: These data suggest that the
      expression of interleukin-2 (IL-2) receptor in maternal T lymphocytes is normally
      suppressed by Trp catabolism, and that either abnormal IDO levels or substances
      influencing IDO activity might lead to non-adequate immune responses on sperm,
      harm the conceptus or even initiate fetal rejection.

PMID- 14672334
TI  - Evidence for a correlation between trophoblast invasiveness and STAT3 activity.
AB  - PROBLEM: Extravillous trophoblast cells are capable of invading decidual tissue
      during early pregnancy. This property is reminiscent of cancer cells. The
      invasiveness of trophoblasts, however, extends only to a well-regulated limit.
      Signal transduction processes underlying this phenomenon are as yet poorly
      characterized. Many factors involved in trophoblast invasiveness are known to
      trigger intracellular signaling cascades in other cell types that ultimately lead
      to the activation of signal transducers and activators of transcription (STATs).
      STAT3 activity was recently found related to the malignant phenotype of different
      tumor cells and potentially contributes to their invasive properties. METHOD OF
      STUDY: We investigated the status of STAT3 activity in ex vivo trophoblast cells
      from first trimester and term placentae employing an electrophoretic mobility
      shift assay (EMSA) and compared it with that of a highly malignant
      choriocarcinoma cell line. RESULTS: Specific DNA binding activity of two STAT3
      variants (STAT3alpha and beta) was observed in immature trophoblasts and appeared
      to be lost in term placentae. The malignant phenotype of choriocarcinoma cells
      coincides with a high degree of STAT3 activity. CONCLUSION: These results suggest
      a connection between STAT3 activity and trophoblast invasiveness.

PMID- 14672335
TI  - Identification of CD4-independent HIV receptors on spermatozoa.
AB  - PROBLEM: Human immunodeficiency virus (HIV) has been demonstrated to bind and
      enter into the spermatozoa facilitating the transmission into urogenital cells.
      However, spermatozoa has been reported to be devoid of the conventional CD4
      receptors for HIV. This suggests that there exists an alternate modality of HIV
      entry into spermatozoa using receptors other than CD4. Present communication
      describes the identification of HIV receptors on the spermatozoa. METHOD OF
      STUDY: The sperm proteins were solubilized using Triton X-100 and subjected to
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western
      blot analysis, using cell-free HIV or gp120 envelope glycoprotein as a probe. HIV
      or gp120 bound protein band was then visualized by using alkaline phosphatase
      (AP) labeled anti-gp120 antibody as well as by using anti-gp120 antibody and
      subsequently by AP-labeled anti-rabbit gamma globulin. RESULTS: The results
      obtained demonstrate for the first time that cell-free HIV and gp120 protein bind
      specifically to 160 kDa sperm protein that could be the receptor for HIV entry
      into spermatozoa. CONCLUSION: A 160 kDa sperm protein could be the CD4
      independent HIV receptor for HIV to bind and enter into the spermatozoa. Further
      characterization of this 160 kDa HIV receptor on sperm will provide an insight in
      understanding the mechanism and probable mode of intervention or prevention of
      HIV transmission at the initial stage of infection.

PMID- 14672336
TI  - Down-regulation of HLA-G1 cell surface expression in human cytomegalovirus
      infected cells.
AB  - PROBLEM: Down-modulation of human leukocyte antigen (HLA)-G1 cell surface
      expression by human cytomegalovirus (HCMV) has only been studied in cellular
      models expressing independent unique short (US) recombinant proteins, but not in
      the context of viral infection. To explore the level of HLA-G1 cell surface
      expression after HCMV infection and to investigate the influence of US viral
      proteins, we infected HLA-G1 expressing cells by HCMV laboratory strains. METHOD
      OF STUDY: Human U373-MG astrocytoma cells were transfected with HLA-G1 cDNA.
      Following HCMV infection, HLA-G1 cell surface expression of these transfectants
      was evaluated by flow cytometry and confocal microscopy, using an HLA-G specific
      monoclonal antibody, and compared with that of uninfected cells. US-deleted
      viruses were then used to evaluate the implication of US proteins. RESULTS: Using
      flow cytometry, it was found that HCMV infection of U373-G1 cells decreased HLA
      G1 cell surface expression. Similar results were obtained with two different HCMV
      strains, namely Towne and AD169. Two color confocal microscopy staining further
      confirmed such HLA-G down-modulation in HCMV-infected cells stained for immediate
      early (IE1/2) nuclear proteins expression. Infection of U373-G1 cells with US
      deleted HCMV strain had no effect on the level of cell surface HLA-G1 expression,
      thus demonstrating the US dependency of the HCMV-mediated down-regulation of HLA
      G1. CONCLUSION: HCMV infection down-modulates HLA-G1 expression at the cell
      surface. This is likely to have functional consequences in case of HCMV uterine
      infection during pregnancy.

PMID- 14672337
TI  - No difference in natural-killer-T cell population, but Th2/Tc2 predominance in
      peripheral blood of recurrent aborters.
AB  - PROBLEM: The aim of this study was to assess the natural-killer-T (NKT) cell
      population and cytokine expression in the peripheral blood of women with a
      history of recurrent spontaneous abortion (RSA). METHOD OF STUDY: The percentages
      of CD3+ CD4- CD8- TCRValpha24+ Vbeta11+-NKT cells and cells expressing
      intracellular interferon (IFN)-gamma, interleukin (IL)-4, and tumor necrosis
      factor (TNF)-alpha either with CD4+ or CD8+ cells were measured by flow cytometry
      at the midluteal phases in 15 RSA women and 15 fertile control women. RESULTS: No
      significant differences in the NKT cell percentages were found between RSA and
      control women. However, in RSA women, the CD4+ IL-4+ cell and CD8+ IL-4+ cell
      percentages were significantly higher, and the Th1/Th2 and Tc1/Tc2 cell ratios
      were significantly lower, than those in the control. CONCLUSIONS: Th2/Tc2
      dominance was found in the general circulation of RSA women; this finding
      provokes a new controversy on the Th1/Th2 balance concerning RSA etiology.

PMID- 14672338
TI  - Increasing circulating T-cell activation markers are linked to subsequent
      implantation failure after transfer of in vitro fertilized embryos.
AB  - PROBLEM: Implantation determines success of in vitro fertilization (IVF) and
      embryo transfer (ET) cycles. Data are accumulating to support a role of the
      immune system in implantation. Most of the literature addresses the importance of
      natural killer (NK) cells in this process. The purpose of the current study is to
      examine the role of circulating T cells in implantation failure. METHOD OF STUDY:
      Blood from 22 women undergoing IVF/ET during November, 2001, was drawn on cycle
      day 9 and analyzed for the percentage of circulating T cells expressing the
      activation markers CD69+ and human leukocyte antigen (HLA)-DR and the suppressor
      marker CD11b using immunofluorescence and flow cytometry. These results were
      compared with total percentage circulating CD3, CD4 and CD8 cells as well as NK
      cells and pregnancy outcome that cycle. RESULTS: Infertile women had
      significantly greater expression of the activation marker of CD69+ among CD8+ and
      CD4+ T cells and HLA-DR among CD4 cells than fertile women. No difference in
      expression of T cell suppressor marker of CD11b was noted when infertile and
      fertile women were compared. No correlations were observed when activated T cells
      were compared with circulating CD3+, CD4+, CD8+, activated NK cells and NK
      cytotoxicity. CD3+ 4+ HLA-DR+ was expressed significantly less among successfully
      pregnant compared with unsuccessfully pregnant women. CONCLUSION: T-cell
      activation markers CD 69+ and HLA-DR+ are associated with increased implantation
      failure after IVF/ET.

PMID- 14672339
TI  - Searching for links between endotoxin exposure and pregnancy loss: CD14
      polymorphism in idiopathic recurrent miscarriage.
AB  - PROBLEM: Lipopolysaccharide (LPS) (endotoxin) is a well-known inducer of
      abortions in mice. In addition it has been proposed that gut-derived LPS of gram
      negative bacteria may play a role in triggering idiopathic recurrent miscarriage
      (IRM) in humans. CD14 is one of the key molecules that mediates the effects of
      LPS. Promoter region polymorphism (-159C/T) in the CD14 gene is functionally
      important by regulating CD14 levels. High-producing CD14 genotype (TT) associates
      with deleterious effects of gut-derived LPS in hepatic cirrhosis in humans. It is
      not known whether women with IRM are genetically more prone to suffer from toxic
      effects of LPS. METHOD OF STUDY: By using polymerase chain reaction we analyzed
      the CD14 promoter region polymorphism in 38 women with IRM and in 127 normal
      controls of Finnish origin. RESULTS: There were no significant differences in the
      CD14 (-159C/T) allele or the genotype frequencies between the IRM women and the
      controls. However, there was a trend associating the presence of the T allele
      with increased odds of miscarriage. CONCLUSIONS: Although we were not able to
      find a statistically significant association between CD14 genotypes and IRM in
      our relatively small study population, a further study with a larger sample size
      is warranted to explore the role of high-producing CD14 genotypes in IRM. Also
      studies highlighting environmental LPS triggers and other intrinsic mediators of
      LPS signalling are needed to solve the enigmatic role of LPS in IRM in humans.

PMID- 14672340
TI  - Pre-conceptional natural killer cell activity and percentage as predictors of
      biochemical pregnancy and spontaneous abortion with normal chromosome karyotype.
AB  - PROBLEM: The aim of the present study was to determine whether pre-conceptional
      natural killer (NK) cell activity and percentage are predictive of subsequent
      spontaneous abortion in women with recurrent spontaneous abortion (RSA). METHOD
      OF STUDY: Pre-conceptional NK cell activity and percentage in peripheral blood of
      women who had a history of two or more RSA was prospectively assessed. The 51Cr
      release assay and flow cytometric analysis were performed. A total of 113 RSA
      women were recruited, and 85 conceived later. RESULTS: Pre-conceptional NK cell
      activity/percentage values in women whose next pregnancies ended in biochemical
      pregnancy and spontaneous abortion with normal fetal karyotype (n = 17, median
      47%/17.1%), but spontaneous abortion with abnormal karyotype (n = 9, 27%/15.7%),
      were higher than those in live births (n = 59, 33%/13.1%). High values of pre
      conceptional NK cell activity (> 46%; relative risk 3.6, 95%CI 1.6-8.0) and
      percentage (> 16.4%; 4.9, 1.7-13.8) were found to predict biochemical pregnancy
      and spontaneous abortion with normal karyotype in the next pregnancy. CONCLUSION:
      Pre-conceptional NK cell abnormalities were predictive of spontaneous abortion
      with normal fetal karyotype.

PMID- 14672341
TI  - Relation between post-partum liver dysfunction and anti-cytochrome 2D6
      antibodies.
AB  - PROBLEM: Autoimmune thyroid disease frequently aggravates or develops after
      delivery through the immune rebound mechanism. However, little is known about the
      post-partum development of autoimmune hepatitis (AIH). METHOD OF STUDY: We
      examined 18 patients who developed liver dysfunction after delivery or abortion.
      Serial examinations were performed in 10 of these cases. Anti-cytochrome
      2D6(CYP2D6) antibodies, which are liver-specific autoantibodies, were measured
      using a sensitive radioligand assay. RESULTS: Liver dysfunction developed between
      1 and 5 months after delivery and was mild and transient except in one case. One
      patient developed liver dysfunction after abortion. Eight of 10 patients who
      underwent serial serologic examinations were positive for anti-nuclear
      antibodies, but anti-smooth muscle antibodies were positive in only three
      patients, and were present only at low titer. None of the patients had anti
      mitochondrial antibodies. Nine of these 10 cases were diagnosed as definite or
      probable AIH according to the international scoring system of AIH. Nine of these
      10 patients were positive for anti-CYP2D6 antibodies. The increase of anti-CYP2D6
      antibodies was slightly delayed compared to increase of aminotransferase. Of the
      18 patients who developed liver dysfunction, 15 cases (83.3%) were positive for
      anti-CYP2D6 antibodies. Of the 77 post-partum control subjects only three (3.9%)
      had positive antibodies. CONCLUSIONS: Autoimmune hepatitis developed after
      delivery, similarly to the development of post-partum autoimmune thyroid disease.
      Measurement of anti-CYP2D6 antibodies by a sensitive radioligand assay could
      provide information important for the detection of post-partum AIH.

PMID- 14672342
TI  - Antinuclear antibody reduces the pregnancy rate in the first IVF-ET treatment
      cycle but not the cumulative pregnancy rate without specific medication.
AB  - PROBLEM: It has been shown that the presence of antinuclear antibody (ANA) might
      reduce pregnancy rates after in vitro fertilization-embryo transfer (IVF-ET).
      However, the mechanism of implantation failure by ANA has not yet been clarified.
      This study was performed to investigate the impact of ANA on pregnancy rates
      after IVF-ET, and the necessity of specific medication for infertile women who
      have ANA in their sera. METHOD OF STUDY: A total of 108 infertile women were
      treated by IVF-ET or intracytoplasmic sperm injection (ICSI)-ET. ANA was examined
      by an indirect fluorescent antibody procedure. Data from women under 40 years old
      were analyzed retrospectively. RESULTS: The implantation rates per embryo
      transferred in the first treatment cycles were 14.8% (eight of 54) and 32.4% (33
      of 102), in women with and without ANA, respectively. There was a significant
      difference in the implantation rates between the two groups (P < 0.05). The
      pregnancy rates per ET in the first treatment cycles were 28% (seven of 25) and
      54.2% (26 of 48), respectively. There was also a significant difference in the
      pregnancy rates between the two groups (P < 0.05). Afterwards, treatments with
      IVF-ET or ICSI-ET were repeatedly performed for unsuccessful patients, without
      any specific medication for ANA. The average ET cycles were 1.80 +/- 1.13 and
      1.27 +/- 0.54, in women with and without ANA, respectively. The cumulative
      pregnancy rates per patient were 68% (17 of 25) and 55.6% (35 of 63),
      respectively. There was no significant difference in the overall pregnancy rates
      between the two groups. CONCLUSIONS: These findings suggest that ANA might have
      an impact on implantation failure in women treated by IVF-ET or ICSI-ET. ANA
      reduced the pregnancy rates in the first IVF-ET or ICSI-ET cycles but not the
      cumulative pregnancy rates without medication. This indicates that the mechanisms
      of implantation failure by ANA could be solved, and effective and safe medication
      should be developed for better implantation rates, especially in the first
      treatment cycle.

PMID- 14672343
TI  - Disorders associated with acute rapid and severe bone loss.
AB  - We describe a constellation of bone diseases characterized by the common feature
      of acute, rapid, and severe bone loss accompanied by dramatic fracture rates.
      These disorders are poorly recognized, resulting mainly from systemic diseases,
      frailty, immobilization, and immunosuppressive drugs, such as glucocorticoids and
      the calcineurin inhibitors. The opportunity to prevent or treat fractures is
      commonly missed because they are often not detected. Ideally, patients need to be
      identified early and preventative therapy initiated promptly to avoid the rapid
      bone loss and fractures. The most effective therapy at present seems to be the
      bisphosphonates, particularly when bone resorption is predominant. However, more
      severe forms of bone loss that result from an osteoblastic defect and reduced
      bone formation may benefit potentially more from newer anabolic agents, such as
      recombinant human parathyroid hormone (rhPTH).

PMID- 14672344
TI  - Idiopathic hyperphosphatasia and TNFRSF11B mutations: relationships between
      phenotype and genotype.
AB  - Homozygous mutations in TNFRSF11B, the gene encoding osteoprotegerin, were found
      in affected members from six of nine families with idiopathic hyperphosphatasia.
      The severity of the phenotype was related to the predicted effects of the
      mutations on osteoprotegerin function. INTRODUCTION: Idiopathic hyperphosphatasia
      (IH) is a rare high bone turnover congenital bone disease in which affected
      children are normal at birth but develop progressive long bone deformities,
      fractures, vertebral collapse, skull enlargement, and deafness. There is,
      however, considerable phenotypic variation from presentation in infancy with
      severe progressive deformity through to presentation in late childhood with
      minimal deformity. Two recent reports have linked idiopathic hyperphosphatasia
      with deletion of, or mutation in, the TNFRSF11B gene that encodes osteoprotegerin
      (OPG), an important paracrine modulator of RANKL-mediated bone resorption.
      MATERIALS AND METHODS: We studied subjects with a clinical diagnosis of IH and
      unaffected family members from nine unrelated families. Clinical, biochemical,
      and radiographic data were collected, and genomic DNA examined for mutations in
      TNFRSF11B. The relationship between the mutations, their predicted effects on OPG
      function, and the phenotype were then examined. RESULTS: Of the nine families
      studied, affected subjects from six were homozygous for novel mutations in
      TNFRSF11B. Their parents were heterozygous, consistent with autosomal recessive
      inheritance. Four of the six mutations occurred in the cysteine-rich ligand
      binding domain and are predicted to disrupt binding of OPG to RANKL. Missense
      mutations in the cysteine residues, predicted to cause major disruption to the
      ligand-binding region, were associated with a severe phenotype (deformity
      developing before 18 months age and severe disability), as was a large deletion
      mutation. Non-cysteine missense mutations in the ligand-binding domain were
      associated with an intermediate phenotype (deformity recognized around the age of
      5 years and an increased rate of long bone fracture). An insertion/deletion
      mutation at the C-terminal end of the protein was associated with the mildest
      phenotype. CONCLUSION: Mutations in TNFRSF11B account for the majority of, but
      not all, cases of IH, and there are distinct genotype-phenotype relationships.

PMID- 14672345
TI  - Both hPTH(1-34) and bFGF increase trabecular bone mass in osteopenic rats but
      they have different effects on trabecular bone architecture.
AB  - Osteoporosis is a syndrome of excessive skeletal fragility that results from both
      the loss of trabecular bone mass and trabecular bone connectivity. Recently, bFGF
      has been found to increase trabecular bone mass in osteoporotic rats. The purpose
      of this study was to compare how trabecular bone architecture, bone cell
      activity, and strength are altered by two different bone anabolic agents, bFGF
      and hPTH(1-34), in an osteopenic rat model. MATERIALS AND METHODS: Six-month-old
      female Sprague-Dawley rats (n = 74) were ovariectomized (OVX) or sham-operated
      (sham) and maintained untreated for 2 months. Then OVX rats were subcutaneously
      injected with basic fibroblast factor (bFGF; 1 mg/kg, 5 days/week), human
      parathyroid hormone [hPTH(1-34); 40 microg/kg, 5 days/week], or vehicle for 60
      days (days 60-120). Sham-operated and one group of OVX animals were injected with
      vehicle. Biochemical markers of bone turnover (urinary deoxypyridinoline cross
      links; Quidel Corp., San Diego, CA, USA) and serum osteocalcin (Biomedical
      Technologies, Stroughton, MA, USA) were obtained at study days 0, 60, 90, and 120
      and analyzed by ELISA. At death, the right proximal tibial metaphysis was
      removed, and microcomputed tomography was performed for trabecular bone structure
      and processed for histomorphometry to assess bone cell activity. The left
      proximal tibia was used for nanoindentation/mechanical testing of individual
      trabeculae. The data were analyzed with Kruskal Wallis and post hoc testing as
      needed. RESULTS: Ovariectomy at day 60 resulted in about a 50% loss of trabecular
      bone volume compared with sham-treated animals. By day 120 post-OVX, OVX +
      vehicle treated animals had decreased trabecular bone volume, connectivity,
      number, and high bone turnover compared with sham-operated animals [p < 0.05 from
      sham-, hPTH(1-34)-, and bFGF-treated groups]. Treatment of OVX animals with bFGF
      and hPTH(1-34) both increased trabecular bone mass, but hPTH(1-34) increased
      trabecular thickness and bFGF increased trabecular number and connectivity.
      Histomorphometry revealed increased mineralizing surface and bone formation rate
      in both bFGF and hPTH(1-34) animals. However, osteoid volume was greater in bFGF
      treated animals compared with both the hPTH(1-34) and OVX + vehicle animals (p <
      0.05). Nanoindentation by atomic force microscope was performed on approximately
      20 individual trabeculae per animal (three animals per group) and demonstrated
      that elastic modulus and hardness of the trabeculae in bFGF-treated animals were
      similar to that of the hPTH-treated and sham + vehicle-treated animals.
      CONCLUSION: Both hPTH(1-34) and bFGF are anabolic agents in the osteopenic female
      rat. However, hPTH(1-34) increases trabecular bone volume primarily by thickening
      existing trabeculae, whereas bFGF adds trabecular bone mass through increasing
      trabecular number and trabecular connectivity. These results suggest the
      possibility of sequential treatment paradigms for severe osteoporosis.

PMID- 14672346
TI  - Trabecular bone response to mechanical and parathyroid hormone stimulation: the
      role of mechanical microenvironment.
AB  - Bone response under combined mechanical and PTH stimuli is important in
      osteoporosis. A rat tail animal model with computer modeling was used to examine
      bone response to loading and PTH. PTH enhances and sustains increased bone
      formation rate, which directly correlates to mechanical microenvironment,
      suggesting beneficial effects of combined PTH treatment and exercise in
      preventing osteoporosis. INTRODUCTION: Using an in vivo rat tail vertebra model
      combined with a specimen-specific, high-resolution microcomputed tomography
      (microCT)-based finite element analysis (FEA) technique, trabecular bone response
      to combined dynamic compressive loading and parathyroid hormone (PTH) stimulation
      was characterized. MATERIALS AND METHODS: Two hundred twenty-four male Sprague
      Dawley rats were randomly divided into seven treatment groups: (1) Control, (2)
      vehicle + 0N, (3) PTH + 0N, (4) vehicle + 50N, (5) PTH + 50N, (6) vehicle + 100N,
      and (7) PTH + 100N, with three treatment durations (1, 2, or 4 weeks). Rat PTH(1
      34) was administered daily in the PTH-stimulated groups approximately 3 h before
      daily mechanical stimulation with 0, 50, or 100N dynamic compressive loading.
      microCT-based FEA was performed for each loaded vertebra after death. Bone
      histomorphometry was performed on trabecular bone with double fluorochrome
      labeling to assess bone formation. RESULTS: Daily mechanical loading or PTH
      administration significantly increased bone formation rate (BFR) compared with
      control or V + 0N with significant increases in both mineral apposition rate
      (MAR) and labeled bone surface (LS/BS). PTH, when combined with mechanical
      loading, enhanced BFR mainly through a significant increase in MAR after the
      first week and through a significant increase in LS/BS after 2 and 4 weeks.
      Synergistic effects in BFR were present when PTH was combined with mechanical
      loading, especially after 2 and 4 weeks, where the increase in BFR was sustained.
      However, when either PTH or mechanical loading was the only stimulus, the bone
      formation response diminished to the level of Control animals after 4 weeks.
      Furthermore, significant correlations were observed between the bone formation
      indices and trabecular bone tissue mechanical microenvironments at 1 and 2 weeks,
      with PTH administration enhancing and sustaining these correlations into 4 weeks.
      CONCLUSIONS: The synergistic effects of combined PTH and mechanical stimulation
      on trabecular bone formation rate suggest a potential benefit for combined PTH
      administration and exercise in the treatment of osteoporosis.

PMID- 14672347
TI  - Overexpression of Nell-1, a craniosynostosis-associated gene, induces apoptosis
      in osteoblasts during craniofacial development.
AB  - We studied the cellular function of Nell-1, a craniosynostosis-related gene, in
      craniofacial development. Nell-1 modulates calvarial osteoblast differentiation
      and apoptosis pathways. Nell-1 overexpression disrupts these pathways resulting
      in craniofacial anomalies such as premature suture closure. INTRODUCTION:
      Craniosynostosis (CS), one of the most common congenital craniofacial
      deformities, is the premature closure of cranial sutures. Previously, we reported
      NELL-1 as a novel molecule overexpressed during premature cranial suture closure
      in patients with CS. Nell-1 overexpression induced calvarial overgrowth and
      resulted in premature suture closure in a rodent model. On a cellular level, Nell
      1 is suggested to promote osteoblast differentiation. MATERIALS AND METHODS:
      Different levels of Nell-1 were introduced into osteoblastic cells by viral
      infection and recombinant protein. Apoptosis and gene expression assays were
      performed. Mice overexpressing Nell-1 were examined for apoptosis. RESULTS: In
      this report, we further showed that overexpression of Nell-1 induced apoptosis
      along with modulation of apoptosis-related genes. The induction of apoptosis by
      Nell-1 was observed only in osteoblastic cells and not in NIH3T3 or primary
      fibroblasts. The CS mouse model overexpressing Nell-1 showed increased levels of
      apoptosis in the calvaria. CONCLUSION: We show that Nell-1 expression modulates
      calvarial osteoblast differentiation and apoptosis pathways. Nell-1
      overexpression disrupts these pathways resulting in craniofacial anomalies such
      as premature suture closure.

PMID- 14672348
TI  - Functional characterization of two naturally occurring mutations in the human
      sodium-phosphate cotransporter type IIa.
AB  - Mutations in the gene encoding the human sodium-phosphate cotransporter (NPT2),
      causing reduced phosphate affinity and dominant-negative behavior, were
      described. We found no evidence of altered kinetics or dominant-negative effects.
      Thus, the mutations cannot account for the clinical phenotype. INTRODUCTION:
      Mutations in NPT22a, the gene encoding the sodium-phosphate cotransporter NaPi
      IIa, were for the first time linked to human disease by Prie and colleagues. Two
      patients are described with renal phosphate wasting who were heterozygous for
      either the A48F or V147M mutation. Expressed in Xenopus oocytes, both mutants
      showed reduced phosphate affinity. Furthermore, coexpression of mutants with
      wildtype (WT) NaPi-IIa resulted in reduced cotransport function, explaining the
      mutants' dominant-negative effect in the patients. Intrigued by the implications
      of these findings on transporter kinetics, we decided to examine the transport
      characteristics of the two mutants in more detail. MATERIALS AND METHODS: We
      recreated the two mutants, expressed them in Xenopus oocytes, and analyzed their
      kinetic behavior by two-electrode voltage clamp. We also performed coexpression
      experiments where we injected mRNA for WT and mutants containing an additional
      S462C mutation, enabling complete inhibition of cotransport function with
      cysteine-modifying reagents. Finally, we expressed WT and mutant NaPi-IIa as C
      terminal fusions to green fluorescent protein (GFP) in opossum kidney (OK) cells.
      RESULTS AND CONCLUSIONS: We found in our oocyte expression experiments that P(i)
      induced currents were reduced in both mutants, whereas P(i) and Na affinities and
      other transport characteristics were not affected. The amount of cotransport
      activity remaining after cysteine modification, corresponding to WT activity, was
      not affected by coexpression of either mutant. Finally, GFP-tagged WT and mutants
      were expressed at the apical membrane in OK cells, showing that both mutants are
      correctly targeted in a mammalian cell. In conclusion, our data from oocyte and
      OK cell expression studies suggest that the heterozygous A48F and V 147M
      mutations cannot explain the pathological phenotype observed by Prie and
      colleagues.

PMID- 14672349
TI  - Deletion mutants of BMP folding variants act as BMP antagonists and are efficient
      inhibitors for heterotopic ossification.
AB  - Heterotopic ossification is a frequent complication in patients who have suffered
      head and neck traumas or have undergone total hip replacement. In this report,
      stable folding variants of the natural occurring osteoinductive BMPs were shown
      to act as inhibitors for heterotopic ossification. The most effective BMP folding
      variant construct performed even better than the natural occurring BMP antagonist
      Noggin because it also inhibited calcium deposition of pre-osteoblastic cells.
      INTRODUCTION: Signal transduction through receptor and ligand binding depends on
      the proper folding of all partners, especially when it involves the formation of
      a heterotetramer. In the case, the receptor binding of the ligand can be
      uncoupled from signal transduction, and folding variants of a ligand can be
      developed into antagonists of the natural bioactivity of the ligand. Here we
      present a deletion mutant of a bone morphogenetic protein (BMP) folding variant
      capable of inhibiting the bone-inducing action of natural occurring BMPs.
      MATERIALS AND METHODS: Deletion mutants and site-directed mutants of BMP folding
      variants were generated and tested for their ability to reduce alkaline
      phosphatase activity and mineralization in a pre-osteoblastic cell line. In vivo
      activity of the optimized folding variant was determined in a heterotopic
      ossification model in rodents and in two Xenopus laevis model systems. Biosensor
      interaction analysis was used to determine the affinity of the optimized BMP
      folding variant to the extracellular domain of BMP receptors. RESULTS: In vitro
      and in vivo tests in rodents revealed that the structural elements of the wrist
      epitope combined with finger 2 and a positive charge proximal to the tip of this
      finger are sufficient to induce osteoinhibition with deletion mutants and folding
      variants of mature BMP-4. The inhibitor designed to suppress heterotopic
      ossification showed BMP antagonist activity in embryos and animal caps of X.
      laevis. Binding studies of the inhibitor to ectodomains of type I and type II BMP
      receptors revealed a concentration-dependent binding, especially to the high
      affinity BMP receptor. CONCLUSIONS: Deletion mutants of BMP folding variants are
      a new form of BMP antagonists and act through competition with osteoinductive BMP
      for BMP receptor binding. The excellent in vivo performance of the optimized
      folding variant is because of its ability to block signaling of endogenous BMPs
      deposited in the extracellular matrix even more effectively than the natural
      occurring BMP antagonist Noggin.

PMID- 14672350
TI  - Biglycan deficiency interferes with ovariectomy-induced bone loss.
AB  - Biglycan is a matrix proteoglycan with a possible role in bone turnover. In a 4
      week study with sham-operated or OVX biglycan-deficient or wildtype mice, we show
      that biglycan-deficient mice are resistant to OVX-induced trabecular bone loss
      and that there is a gender difference in the response to biglycan deficiency.
      INTRODUCTION: Biglycan (bgn) is a small extracellular matrix proteoglycan
      enriched in skeletal tissues, and biglycan-deficient male mice have decreased
      trabecular bone mass and bone strength. The purpose of this study was to
      investigate the bone phenotype of the biglycan-deficient female mice and to
      investigate the effect of estrogen depletion by ovariectomy (OVX). MATERIALS AND
      METHODS: OVX or sham operations were performed on 21-week-old mice that were
      divided into four groups: wt sham (n = 7), wt OVX (n = 9), bgn-deficient sham (n
      = 10) and bgn-deficient OVX (n = 10). The mice were killed 4 weeks after surgery.
      Bone mass and bone turnover were analyzed by peripheral quantitative computed
      tomography (pQCT), biochemical markers, and histomorphometry. RESULTS AND
      CONCLUSIONS: In contrast to the male mice, there were only few effects of bgn
      deficiency on bone metabolism in female mice, showing a clear gender difference.
      However, when stressed by OVX, the female bgn knockout (KO) mice were resistant
      to the OVX-induced trabecular bone loss. The wt mice showed a decrease in
      trabecular bone mineral density by pQCT measurements, a decrease in trabecular
      bone volume (BV/TV), and an increase in mineral apposition rate. In contrast, no
      significant changes were detected in bgn KO mice after OVX. In addition, analysis
      of the bone resorption marker deoxypyridinoline showed no significant increase in
      the bgn KO OVX mice compared with bgn KO sham mice. Measurements of serum
      osteoprotegerin (OPG) and RANKL revealed increased levels of OPG and decreased
      levels of RANKL in the bgn KO mice compared with wt mice. In conclusion, the bgn
      deficiency protects against increased trabecular bone turnover and bone loss in
      response to estrogen depletion, supporting the concept that bgn has dual roles in
      bone, where it may modulate both formation and resorption ultimately influencing
      the bone turnover process.

PMID- 14672351
TI  - 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibits osteoclastogenesis by
      suppressing RANKL-induced NF-kappaB activation.
AB  - The mechanism by which TPA-induced PKC activity modulates osteoclastogenesis is
      not clear. Using a RAW(264.7) cell culture system and assays for NF-kappaB
      nuclear translocation, NF-kappaB reporter gene activity, and MAPK assays, we
      demonstrated that TPA inhibits osteoclastogenesis through the suppression of
      RANKL-induced NF-kappaB activation. INTRODUCTION: The protein kinase C (PKC)
      pathway has been suggested to be an important regulator of osteoclastic bone
      resorption. The role of PKC in RANKL-induced osteoclastogenesis, however, is not
      clear. In this study, we examined the effects of 12-O-tetradecanoylphorbol-13
      acetate (TPA), a PKC activator, on osteoclastogenesis and studied its role in
      RANKL-induced signaling. MATERIALS AND METHODS: RANKL-induced RAW(264.7) cell
      differentiation into osteoclast-like cells was used to assess the effect of TPA
      on osteoclastogenesis. Assays for NF-kappaB nuclear translocation, NF-kappaB
      reporter gene activity, protein kinase activity, and Western blotting were used
      to examine the effects of TPA on RANKL-induced NF-kappaB, c-Jun N-terminal kinase
      (JNK), and MEK/ERK and p38 signal transduction pathways. RESULTS: We found that
      TPA inhibited RANKL-induced RAW(264.7) cell differentiation into osteoclasts in a
      dose-dependent manner. Time course analysis showed that the inhibitory effect of
      TPA on RANKL-induced osteoclastogenesis occurs predominantly at an early stage of
      osteoclast differentiation. TPA alone had little effect on NF-kappaB activation
      in RAW(264.7) cells, but it suppresses the RANKL-induced NF-kappaB activation in
      a dose-dependent fashion. Interestingly, the suppressive effect of TPA on RANKL
      induced NF-kappaB activation was prevented by a conventional PKC inhibitor,
      Go6976. Supershift studies revealed that the RANKL-induced DNA binding of NF
      kappaB complexes consisted of C-Rel, NF-kappaB1 (p50), and RelA (p65). In
      addition, TPA induced the activation of JNK in RAW(264.7) cells but had little
      effect on RANKL-induced activation of JNK. TPA also inhibited RANKL-induced
      activation of ERK but had little effect on p38 activation. CONCLUSION: Given that
      NF-kappaB activation is obligatory for osteoclast differentiation, our studies
      imply that inhibition of osteoclastogenesis by TPA is, at least in part, caused
      by the suppression of RANKL-induced activation of NF-kappaB during an early stage
      of osteoclastogenesis. Selective modulation of RANKL signaling pathways by PKC
      activators may have important therapeutic implications for the treatment of bone
      diseases associated with enhanced bone resorption.

PMID- 14672352
TI  - Shock wave application enhances pertussis toxin protein-sensitive bone formation
      of segmental femoral defect in rats.
AB  - Extracorporeal shock waves (ESWs) elicit a dose-dependent effect on the healing
      of segmental femoral defects in rats. After ESW treatment, the segmental defect
      underwent progressive mesenchymal aggregation, endochondral ossification, and
      hard callus formation. Along with the intensive bone formation, there was a
      persistent increase in TGF-beta1 and BMP-2 expression. Pretreatment with
      pertussis toxin reduced ESW-promoted callus formation and gap healing, which
      presumably suggests that Gi proteins mediate osteogenic signaling. INTRODUCTION:
      Extracorporeal shock waves (ESWs) have previously been used to promote bone
      repair. In our previous report, we found that ESWs promoted osteogenic
      differentiation of mesenchymal cells through membrane perturbation and activation
      of Ras protein. In this report, we show that ESWs elicit a dose-dependent effect
      on the healing of segmental defects and that Gi proteins play an important role
      in mediating ESW stimulation. MATERIALS AND METHODS: Rats with segmental femoral
      defects were subjected to ESW treatment at different energy flux densities (EFD)
      and impulses. Bone mass (mineral density and calcium content), osteogenic
      activities (bone alkaline phosphatase activity and osteocalcin content), and
      immunohistochemistry were assessed. RESULTS: An optimal ESW energy (500 impulses
      at 0.16 mJ/mm2 EFD) stimulated complete bone healing without complications. ESW
      augmented healing was characterized by significant increases (p < 0.01) in callus
      size, bone mineral density, and bone tissue formation. With exposure to ESW,
      alkaline phosphatase activity and osteocalcin production in calluses were found
      to be significantly enhanced (p < 0.05). After ESW treatment, the histological
      changes we noted included progressive mesenchymal aggregation, endochondral
      ossification, and hard callus formation. Intensive bone formation was associated
      with a persistent increase in transforming growth factor-beta 1 (TGF-beta1) and
      bone morphogenetic protein-2 (BMP-2) expression, suggesting both growth factors
      were active in ESW-promoted bone formation. We also found that pertussis toxin,
      an inhibitor of membrane-bound Gi proteins, significantly reduced (p < 0.01) ESW
      promotion of callus formation and fracture healing. CONCLUSION: ESW treatments
      enhanced bone formation and the healing of segmental femoral defects in rats. It
      also seems likely that TGF-beta1 and BMP-2 are important osteogenic factors for
      ESW promotion of fracture healing, presumably through Gi protein-mediated
      osteogenic signaling.

PMID- 14672353
TI  - Role of gastrointestinal hormones in postprandial reduction of bone resorption.
AB  - Collagen type I fragments, reflecting bone resorption, and release of gut
      hormones were investigated after a meal. Investigations led to a dose escalation
      study with glucagon like peptide-2 (GLP-2) in postmenopausal women. We found a
      dose-dependent effect of GLP-2 on the reduction of bone resorption. INTRODUCTION:
      The C-terminal telopeptide region of type I collagen as measured in serum (s-CTX)
      can be used to assess bone resorption. This marker of bone resorption has a
      significant circadian variation that is influenced by food intake. However, the
      mediator of this variation has not been identified. MATERIALS AND METHODS: We
      studied the release of the gut hormones glucose-dependent insulinotropic
      polypeptide (GIP) and glucagon-like peptide-2 (GLP-2; a representative of the
      intestinal proglucagon-derived peptides) after ingestion of glucose, fat,
      protein, and fructose, as well as their effects after parenteral administration
      in relation to bone turnover processes in healthy volunteers. Furthermore, we
      studied the effect on bone turnover of a single subcutaneous injection of GLP-2
      in four different dosages (100, 200, 400, or 800 microg GLP-2) or placebo in 60
      postmenopausal women (mean age, 61 +/- 5 years). RESULTS: All macronutrients
      significantly (p < 0.05) reduced bone resorption as assessed by s-CTX (39-52%
      from baseline), and only the glucagon-like peptides were secreted in parallel.
      Parenteral administration of GIP and GLP-1 did not result in a reduction of the s
      CTX level, whereas GLP-2 caused a statistically significant and dose-dependent
      reduction in the s-CTX level from baseline compared with placebo (p < 0.05).
      Urine DPD/creatinine, a marker of bone resorption, was significantly reduced by
      25% from baseline in the 800-microg GLP-2 group (p < 0.01). An area under the
      curve (AUC(0-8h)) analysis for s-CTX after GLP-2 injection confirmed the dose
      dependent decrease (ANOVA, p = 0.05). The s-osteocalcin level was unaffected by
      the GLP-2 treatment. CONCLUSION: These studies exclude both GIP and GLP-1 as key
      mediators for the immediate reduction in bone resorption seen after a meal. The
      dose-dependent reduction of bone resorption markers found after subcutaneous
      injection of GLP-2 warrants further investigation into the mechanism and
      importance of GLP-2 for the bone turnover processes.

PMID- 14672355
TI  - Interrelationships between structural parameters of cancellous bone reveal
      accelerated structural change at low bone volume.
AB  - This study shows that change to cancellous bone structure is bone volume
      dependent in a nonlinear manner. At low bone volume (< 15%), trabecular thickness
      and trabecular separation change at a much greater rate than at higher bone
      volume. This suggests that the structural integrity of the cancellous bone may
      become rapidly compromised when bone volume falls below a critical value.
      INTRODUCTION: While bone mass is the major determinant of bone strength, this
      mass-based paradigm does not fully account for the contribution of the bone
      microstructure to mechanical efficiency. Geometric models of cancellous bone
      structure have been formulated based on stylized representations of the
      trabecular elements, where the relationships between bone volume and bone surface
      of cancellous bone are complex and reflect the modulating effect on the
      cancellous bone structure of bone remodeling at the trabecular surfaces. Using
      the plate model of cancellous bone structure, the interrelationships between
      parameters of cancellous bone structure have been studied. MATERIALS AND METHODS:
      Two hundred eighty histological sections of human cancellous bone from eight
      skeletal sites were analyzed. The structural parameters of cancellous bone
      (BV/TV, BS/TV, BS/BV, Tb.Th, Tb.Sp, Tb.N, and TBPf) were obtained. RESULTS AND
      CONCLUSIONS: This study shows that change to cancellous bone structure is bone
      volume-dependent in a nonlinear manner. At low bone volume (< 15%), structural
      parameters of cancellous bone, such as trabecular thickness and trabecular
      separation, change at a much greater rate than at higher bone volume. This
      suggests that the structural integrity of the cancellous bone may become rapidly
      compromised when bone volume falls below a critical value. These data describe
      the complex relationships between bone mass and structure in cancellous bone that
      are often overlooked in the mass-based paradigm of bone strength.
      Histomorphometric descriptors of cancellous bone structure highlight the
      potential for accelerated deterioration of the structure with low bone volume,
      which leads to increased risk of fracture. From a clinical viewpoint, estimation
      of an individual's fracture risk is constrained to noninvasive techniques, which
      only provide bone mineral density or bone mineral content. Therefore, there is a
      need to better correlate measurement of bone mass with measurements of structural
      parameters.

PMID- 14672354
TI  - Bone histomorphometric changes after liver transplantation for chronic
      cholestatic liver disease.
AB  - Thirty-three patients with cholestatic liver disease underwent histomorphometric
      assessment of paired bone biopsy specimens at time of orthotopic liver
      transplantation (OLT) and 4 months thereafter. At 4 months after OLT, bone
      metabolism improved, with bone formation increasing to normal and no change in
      bone resorption. Early post-transplant bone loss may be attributed to an
      additional insult to bone formation early after transplantation. INTRODUCTION:
      Patients with advanced liver disease, especially chronic cholestasis, often have
      osteopenia, which worsens early after orthotopic liver transplantation (OLT)
      before starting to recover. The changes in bone metabolism leading to this rapid
      loss of bone after OLT, and to its recovery, are poorly defined. MATERIALS AND
      METHODS: In thirty-three patients with advanced chronic cholestatic liver
      disease, tetracycline-labeled bone biopsy specimens were analyzed prospectively
      at time of OLT and at 4 months after OLT, as part of a randomized trial to study
      the efficacy of calcitonin on post-transplant bone loss. Hierarchical cluster
      analysis of histomorphometric parameters was performed in an attempt to establish
      the functional grouping of individual histomorphometric parameters before and
      after OLT. RESULTS AND CONCLUSIONS: Results showed that from the time of OLT to 4
      months after OLT, bone mineral density of the lumbar spine and histomorphometric
      parameters of bone volume decreased, consistent with early post-transplant bone
      loss. Histomorphometric resorption parameters were increased before OLT, with no
      change after OLT. Histomorphometric formation parameters increased from low
      values before OLT to normal values at 4 months after OLT, with the exception of
      mean wall thickness values, which further decreased after OLT, suggesting an
      additional insult to bone formation during the study period. Histomorphometric
      changes after OLT were similar in female and male patients, pre- and
      postmenopausal women, and in patients treated and not treated with calcitonin.
      Hierarchical cluster analysis suggested that before OLT, bone resorption was
      functioning independently of bone formation, but that by 4 months after OLT,
      their coupled relationship had improved. Therefore, despite post-transplant bone
      loss, by 4 months after OLT, bone metabolism had improved, with increased bone
      formation and more coupled bone balance, as suggested by hierarchical cluster
      analysis.

PMID- 14672356
TI  - F-18 NaF PET for detection of bone metastases in lung cancer: accuracy, cost
      effectiveness, and impact on patient management.
AB  - As bone metastases might be present in lung cancer despite a normal bone scan, we
      examined various alternatives prospectively. Positron emission tomography using F
      18 sodium fluoride (PET) and single photon emission tomography (SPECT) were more
      sensitive than a planar bone scan. PET was more accurate with a shorter
      examination time than SPECT but had higher incremental costs. INTRODUCTION:
      Previous studies have shown that vertebral bone metastases not seen on planar
      bone scans may be present on F-18 fluoride positron emission tomography (PET)
      scan or single photon emission computed tomography (SPECT). The purpose of this
      study was to measure the accuracy, clinical value and cost-effectiveness of
      tomographic bone imaging. MATERIALS AND METHODS: A total of 103 patients with
      initial diagnosis of lung cancer was prospectively examined with planar bone
      scintigraphy (BS), SPECT of the vertebral column and PET using F-18 sodium
      fluoride (F-18 PET). Receiver operating characteristic (ROC) curve analysis was
      used for determination of the diagnostic accuracy. A decision-analysis model and
      the national charge schedule of the German Hospital Association were used for
      determination of the cost-effectiveness. RESULTS: Thirteen of 33 patients with
      bone metastases were false negative on BS, 4 on SPECT, and 2 on F-18 PET. The
      area under the ROC curve was 0.771 for BS, 0.875 for SPECT, and 0.989 for F-18
      PET (p < 0.05). As a result of SPECT and F-18 PET imaging, clinical management
      was changed in 8 (7.8%) and 10 (9.7%) patients. Compared with BS, the costs per
      additional correctly diagnosed patient were 1272 Euro with SPECT and 2861 Euro
      with F-18 PET. The threshold for the costs of F-18 PET being more cost-effective
      than SPECT was 345 EUR. CONCLUSION: Routine performance of tomographic bone
      imaging improves the therapeutic strategy because of detection of otherwise
      missed metastases. F-18 PET is more effective than SPECT but is associated with
      higher incremental costs.

PMID- 14672357
TI  - A prospective study of risedronate on regional bone metabolism and blood flow at
      the lumbar spine measured by 18F-fluoride positron emission tomography.
AB  - The effect of risedronate on bone metabolism at the lumbar spine was assessed in
      18 women who had a 18F-fluoride PET scan at baseline and after 6 months of
      therapy. The net plasma clearance of fluoride to bone mineral reflecting
      osteoblastic activity decreased significantly after therapy. INTRODUCTION:
      Quantitative radionuclide studies of bone reflect bone blood flow and regional
      osteoblastic activity, and the latter should change after treatment with a
      bisphosphonate, although this has not been previously demonstrated. The aim of
      this study was to examine regional 18F-fluoride kinetics in the lumbar spine
      measured by 18F-fluoride positron emission tomography (PET) before and after
      treatment with risedronate. MATERIALS AND METHODS: Eighteen women, with a mean
      age of 67.0 years and a T-score of less than -2 at the spine or hip, had a
      dynamic PET scan of the lumbar spine after the injection of 90 MBq 18F-fluoride
      ion at baseline and 6 months after commencing risedronate therapy. The arterial
      plasma input function was derived using aorta arterial activity from the PET
      image. Time-activity curves were measured by placing regions of interest over the
      lumbar vertebrae. A three-compartmental model was used to calculate bone blood
      flow (K(1)) and the net plasma clearance of tracer to bone mineral (K(i)). Rate
      constants k(2), k(3), and k(4), which describe transport between plasma, the
      extracellular fluid (ECF) compartment, and the bone mineral compartment,
      respectively, were also measured. RESULTS: Mean vertebral K(i) decreased
      significantly by 18.4% from baseline (3.32 x 10(-2) ml/min/ml) to 6 months post
      treatment (2.71 x 10(-2) ml/min/ml; p = 0.04). This decrease was similar in
      magnitude to the decrease observed for bone-specific alkaline phosphatase, a
      marker of bone formation. There was no significant difference in K(1) from
      baseline (1.49 x 10(-1) ml/min/ml) to 6 months after treatment (1.38 x 10(-1)
      ml/min/ml; p > 0.05). There was a significant increase in k(2), reflecting the
      reverse transport of fluoride from the extravascular tissue compartment to
      plasma, after 6 months of treatment (2.90 x 10(-1)/min versus 4.43 x 10(-1)/min;
      p = 0.01). No significant changes were seen for k(3) or k(4). There was a
      significant decrease from baseline in the fraction of tracer in the extravascular
      tissue space that underwent specific binding to the bone matrix (k(3)/[k(2) +
      k(3)]), decreasing by 18.1% (p = 0.02). CONCLUSION: K(i), the net plasma
      clearance to bone mineral reflecting regional osteoblastic activity, displayed a
      significant decrease after 6 months of antiresorptive therapy. This is the first
      study to show a direct metabolic effect of antiresorptive therapy on skeletal
      kinetics at the clinically important site of the lumbar spine. The use of 18F
      fluoride PET may provide a useful noninvasive tool to assess novel treatments
      currently being developed for osteoporosis.

PMID- 14672358
TI  - Evaluation of treadmill exercise in a lower body negative pressure chamber as a
      countermeasure for weightlessness-induced bone loss: a bed rest study with
      identical twins.
AB  - Counteracting bone loss is required for future space exploration. We evaluated
      the ability of treadmill exercise in a LBNP chamber to counteract bone loss in a
      30-day bed rest study. Eight pairs of identical twins were randomly assigned to
      sedentary control or exercise groups. Exercise within LBNP decreased the bone
      resorption caused by bed rest and may provide a countermeasure for spaceflight.
      INTRODUCTION: Bone loss is one of the greatest physiological challenges for
      extended-duration space missions. The ability of exercise to counteract
      weightlessness-induced bone loss has been studied extensively, but to date, it
      has proven ineffective. We evaluated the effectiveness of a combination of two
      countermeasures-treadmill exercise while inside a lower body negative pressure
      (LBNP) chamber-on bone loss during a 30-day bed rest study. MATERIALS AND
      METHODS: Eight pairs of identical twins were randomized into sedentary (SED) or
      exercise/LBNP (EX/LBNP) groups. Blood and urine samples were collected before,
      several times during, and after the 30-day bed rest period. These samples were
      analyzed for markers of bone and calcium metabolism. Repeated measures ANOVA was
      used to determine statistical significance. Because identical twins were used,
      both time and group were treated as repeated variables. RESULTS: Markers of bone
      resorption were increased during bed rest in samples from sedentary subjects,
      including the collagen cross-links and serum and urinary calcium concentrations.
      For N-telopeptide and deoxypyridinoline, there were significant (p < 0.05)
      interactions between group (SED versus EX/LBNP) and phase of the study (sample
      collection point). Pyridinium cross-links were increased above pre-bed rest
      levels in both groups, but the EX/LBNP group had a smaller increase than the SED
      group. Markers of bone formation were unchanged by bed rest in both groups.
      CONCLUSIONS: These data show that this weight-bearing exercise combined with LBNP
      ameliorates some of the negative effects of simulated weightlessness on bone
      metabolism. This protocol may pave the way to counteracting bone loss during
      spaceflight and may provide valuable information about normal and abnormal bone
      physiology here on Earth.

PMID- 14672359
TI  - Gender differences in mortality after hip fracture: the role of infection.
AB  - Possible explanations for the observed gender difference in mortality after hip
      fracture were examined in a cohort of 804 men and women. Mortality during 2 years
      after fracture was identified from death certificates. Men were twice as likely
      as women to die, and deaths caused by pneumonia/influenza and septicemia showed
      the greatest increase. INTRODUCTION: Men are more likely to die after hip
      fracture than women. Gender differences in predisposing factors and causes of
      death have not been systematically studied. MATERIALS AND METHODS: Participants
      (173 men and 631 women) in the Baltimore Hip Studies cohort enrolled in 1990 and
      1991, at the time of hospitalization for hip fracture, were followed
      longitudinally for 2 years. Cause-specific mortality 1 and 2 years after hip
      fracture, identified from death certificates, was compared by gender and to
      population rates. RESULTS AND CONCLUSIONS: Men were twice as likely as women to
      die during the first and second years after hip fracture (odds ratio [OR], 2.28;
      95% CI, 1.47, 3.54 and OR, 2.21; 95% CI, 1.48, 3.31). Prefracture medical
      comorbidity, type of fracture, type of surgical procedure, and postoperative
      complications did not explain the observed difference. Greatest increases in
      mortality, relative to the general population, were seen for septicemia (relative
      risk [RR], 87.9; 95% CI, 16.5, 175 at 1 year and RR, 32.0; 95% CI, 7.99, 127 at 2
      years) and pneumonia (RR, 23.8; 95% CI, 12.8, 44.2 at 1 year and RR, 10.4; 95%
      CI, 3.35, 32.2 at 2 years). The magnitude of increase in deaths caused by
      infection was greater for men than for women in both years. Mortality rates for
      men and women were similar if deaths caused by infection were excluded (3.46
      [1.79, 6.67] and 2.47 [1.63, 3.72] at 1 year and 0.96 [0.48, 1.91] and 1.26
      [0.80, 1.98] at 2 years). Deaths related to infections (pneumonia, influenza, and
      septicemia) seem to be largely responsible for the observed gender difference. In
      conclusion, an increased rate of death from infection and a gender difference in
      rates persists for at least 2 years after the fracture.

PMID- 14672360
TI  - Racial differences in bone mineral density in older men.
AB  - Studies have examined factors related to BMD in older white, but not black, men.
      We measured BMD in older white and black men and examined factors related to
      racial differences in BMD. Black men had significantly higher adjusted BMD at all
      sites. These results may explain, in part, the lower incidence of fractures in
      older black men. INTRODUCTION: Several studies have examined factors associated
      with bone mineral density (BMD)in older men. None, however, have had sufficient
      numbers of black men to allow for meaningful comparisons by race. MATERIALS AND
      METHODS: A total of 503 white and 191 black men aged 65 and older(75.1 +/- 5.8
      and 72.2 +/- 5.7 years, respectively) were recruited from the Baltimore
      metropolitan area. All men completed a battery of self-administered
      questionnaires, underwent a standardized examination, and had BMD measured at the
      femoral neck, lumbar spine, and total body. Data were analyzed using multiple
      variable linear regression models, adjusted for potential confounding variables;
      two-way interactions with main effects were included in models where appropriate.
      RESULTS: Black men had significantly higher adjusted BMD at the femoral neck
      (difference 0.09 [95% CI: 0.07, 0.12] mg/cm2), lumbar spine (0.07 [0.04, 0.10]
      mg/cm2), and total body (0.06 [0.03, 0.08] mg/cm2) than white men. CONCLUSIONS:
      Older black men have significantly higher BMD than older white men, even after
      adjustment for factors associated with BMD. These differences, especially at the
      femoral neck, may explain the reduced incidence of hip fracture in black compared
      with white men.

PMID- 14672361
TI  - Quantitative trait loci on chromosomes 2p, 4p, and 13q influence bone mineral
      density of the forearm and hip in Mexican Americans.
AB  - We performed a genome scan using BMD data of the forearm and hip on 664
      individuals in 29 Mexican-American families. We obtained evidence for QTL on
      chromosome 4p, affecting forearm BMD overall, and on chromosomes 2p and 13q,
      affecting hip BMD in men. INTRODUCTION: The San Antonio Family Osteoporosis Study
      (SAFOS) was designed to identify genes and environmental factors that influence
      bone mineral density (BMD) using data from large Mexican-American families.
      MATERIALS AND METHODS: We performed a genome-wide linkage analysis using 416
      highly polymorphic microsatellite markers spaced approximately 9.5 cM apart to
      locate and identify quantitative trait loci (QTL) that affect BMD of the forearm
      and hip. Multipoint variance components linkage analyses were done using data on
      all 664 subjects, as well as two subgroups of 259 men and 261 premenopausal
      women, from 29 families for which genotypic and phenotypic data were available.
      RESULTS: We obtained significant evidence for a QTL affecting forearm (radius
      midpoint) BMD in men and women combined on chromosome 4p near D4S2639 (maximum
      LOD = 4.33, genomic p = 0.006) and suggestive evidence for a QTL on chromosome
      12q near locus D12S2070 (maximum conditional LOD = 2.35). We found suggestive
      evidence for a QTL influencing trochanter BMD on chromosome 6 (maximum LOD =
      2.27), but no evidence for QTL affecting the femoral neck in men and women
      combined. In men, we obtained evidence for QTL affecting neck and trochanter BMD
      on chromosomes 2p near D2S1780 (maximum LOD = 3.98, genomic p = 0.013) and 13q
      near D13S788 (maximum LOD = 3.46, genomic p = 0.039), respectively. We found no
      evidence for QTL affecting forearm or hip BMD in premenopausal women. CONCLUSION:
      These results provide strong evidence that a QTL on chromosome 4p affects radius
      BMD in Mexican-American men and women, as well as evidence that QTL on
      chromosomes 2p and 13q affect hip BMD in men. Our results are consistent with
      some reports in humans and mice. J Bone Miner Res 2003;18:2245-2252

PMID- 14672362
TI  - Photocatalytic degradation of wastewater pollutants: titanium dioxide mediated
      degradation of methyl orange and beta-naphthol orange.
AB  - The photocatalytic degradation of azo dyes such as methyl orange and beta
      naphthol orange in aqueous suspensions of TiO2 has been investigated under a
      variety of conditions. The kinetics of degradation was studied under different
      conditions such as reaction pH, substrate and catalyst concentration, and types
      of titanium dioxide used and in the presence of electron acceptors and electron
      donors. The degradation rates of the dyes have been found to be strongly
      influenced by all the above parameters. Carbon dioxide yield measurements
      indicate that only partial mineralization occurs in the initial phase of
      oxidation.

PMID- 14672363
TI  - Bioremediation of soil contaminated with organic compounds with special reference
      to acrylonitrile.
AB  - Enrichment of acrylonitrile (AN) degrading bacterial culture from contaminated
      soil resulted in the isolation of two cultures which were identified as gram
      negative small rods (C1) and gram positive cocci (C2). One of the cultures (C1)
      was identified as Citrobacter fruendii on the basis of biochemical and
      physiological tests. Both the cultures (C1 and C2) were able to utilize
      acrylonitrile up to a concentration of 2000 mg/l as the sole source of carbon and
      nitrogen. The studies also confirmed that the acrylonitrile contaminated soil
      when ploughed with well mixed AN degrading culture, diammonium phosphate and
      farmyard manure, could be completely remediated within two months from the date
      of soil amendment.

PMID- 14672364
TI  - Heterogenous solar photocatalysis of two commercial reactive azo dyes.
AB  - Two commercial reactive azo dyes--Reactive Black 5 (RB5) and Reactive Orange 16
      (RO 16) have been treated by titanium dioxide and Zinc oxide photocatalysts
      separately under presence of sunlight. It is observed that solar photocatalytic
      treatment is effective in terms of colour and COD. The photodegradation
      efficiency of zinc oxide is comparable with TiO2 at pH 5-6 for RO16. The extent
      of decolourization and degradation of RB5 is greater in presence of zinc oxide
      photocatalyst than TiO2 at pH 5- 6. Zinc oxide undergoes <1% photodissolution
      after 6 hours of solar irradiation at working pH.

PMID- 14672365
TI  - Diesel particulate abatement via wall-flow traps based on perovskite catalysts.
AB  - It is probably redundant to stress how extensive are nowadays the attempts to
      reduce the diesel particulate emissions from automotive and stationary sources.
      The present paper looks into a technology relied on a catalytic trap based on a
      SiC wall-flow monolith lined with suitable catalysts for the sake of promoting a
      more complete and faster regeneration after particulate capture. All the major
      steps of the catalytic filter preparation are dealt with, including: the
      synthesis and choice of the proper catalyst and trap materials, the development
      of an in situ catalyst deposition technique, the bench testing of the derived
      catalytic wall-flow. The best catalyst selected was the perovskite
      La0.9K0.1Cr0.9O3-delta. The filtration efficiency and the pressure drop of the
      catalytic and non-catalytic monoliths were evaluated on a diesel engine bench
      under various operating conditions.

PMID- 14672366
TI  - Removal of fluoride from fluoride contaminated industrial waste water by
      electrolysis.
AB  - Wastewater containing fluoride are generally treated with lime or calcium salt
      supplemented with aluminium salts. Wastewater generated from different industries
      does not always behave in the same way due to the presence of interfering
      contaminants. A number of techniques have been developed and studied for the
      removal of excessive fluoride. Most of these are based on use of aluminium salt.
      In alum coagulation the sorption properties of product of hydrolysis of aluminium
      salts and capacity of fluoride for complex formation plays a very important role.
      These hydrolysis products of aluminium can be produced by passing direct current
      through aluminium electrode. The text presented in the paper deals with the
      various aspect of removal of fluoride by electrolysis using aluminium electrode
      from fluoride chemical based industrial wastewater.

PMID- 14672367
TI  - Fenton-type treatment: state of the art.
AB  - The different currently used Fenton-type treatments, either chemically or
      electrochemically generated, are reviewed. A particular attention is devoted to
      the traditional Fe++/H2O2 chemical process and to the indirect electrochemical
      oxidation which uses in situ generated hydrogen peroxide. Mechanisms and
      experimental conditions employed for the optimisation of each technology are
      reported; moreover advantages and main limitations are discussed.

PMID- 14672368
TI  - Preliminary studies on bacterial decolorization of H-acid based azo dye-reactive
      black 5.
AB  - A co-culture acclimatized to H-acid was used to degrade Reactive Black 5 (RB 5),
      a bis azo dye having central H-acid function. The effect of substrate
      concentration, pH and medium composition on the decolorization has been
      investigated. Decolorization was found independent of pH. Luria-Bertani broth
      favored decolorization over Yeast Extract; however further decolorization
      experiments have been conducted using Yeast Extract. The Michaelis-Menten Kinetic
      model is found to describe the dependence of specific decolorization rate on the
      RB 5 dye concentration.

PMID- 14672369
TI  - Electrochemical treatment of wastewater from a phosphoric acid manufacturing
      plant.
AB  - Phosphoric acid plant wastewater containing fluoride, phosphate and chemical
      oxygen demand etc., was treated using electrooxidation and electroflocculation
      methods. A maximum of 82% F- and 22.7% COD were removed using Ti/Pt(5c) under
      electrooxidative conditions. Electrooxidation with respect to F- removal is found
      mass-transfer limited, and removals below 5-6 mg/L F- are not achievable.
      Electroflocculation using Al anode resulted in better removal of F-, COD and
      PO4(3-). The various results obtained are discussed in this paper.

PMID- 14672371
TI  - Biohydrolysis of urea from urea-bearing wastewater.
AB  - Biological stabilization of urea is a two staged process; (i) urea hydrolysis and
      (ii) ammonia stripping/nitrification-denitrification. Ammonia thus produced is
      either stripped off by usual methods or after converting into nitrate using
      chemoautotrophic bacteria. On denitrification, nitrate is finally converted into
      nitrogen gas by means of heterotrophic bacteria. Details of stabilization of urea
      from urea bearing wastewater using urea biohydrolyser are presented in this
      paper.

PMID- 14672370
TI  - Rate enhancing effect of bromide on the removal of ammonia at Ti/PbO2 anode.
AB  - Electrochemical oxidation of ammonium (NH4+) at Ti/PbO2 anode in chloride-free
      and chloride containing aqueous solutions was studied. The experimental results
      have shown that oxidation of NH4- is ensured only in the presence of chloride.
      The oxidation of NH4+ is found to follow pseudo first-order kinetics. Bromide in
      the electrolyte is found to cause substantial rate enhancing effect on the
      ammonium removal. The dependence of k on the current density as well as halide
      concentration is also discussed in this study.

PMID- 14672372
TI  - Application of electrochemical reactors for industrial waste-water treatment.
AB  - The effectiveness of electrochemical reactors for industrial wastewater treatment
      has been improved since three-dimensional electrodes have been introduced; in
      fact, limitations of mass transfer can arise, due to the low concentrations of
      pollutants which may be involved in the process. Three-dimensional electrodes
      offer a very high electrode area per unit electrode volume and they can act as
      turbulence promoters or give rise to high linear electrolyte velocity, resulting
      in high values of mass transport coefficient. However, careful selection of
      operative parameters is needed in order to obtain high performance. This paper
      examines the results obtained in our laboratory on the cathodic reduction of
      copper at RVC electrodes; in particular the interference of dissolved oxygen is
      studied during the removal of copper from extremely diluted solutions (C < 10
      ppm). Some results are also discussed on the removal of organic pollutants by
      electrochemical oxidation at three-dimensional anode consisting of a fixed bed of
      carbon pellets.

PMID- 14672373
TI  - Novel photoreactors for heterogeneous photocatalytic wastewater treatment.
AB  - Heterogeneous photocatalysis is an effective treatment method for removal of
      toxic pollutants from industrial wastewaters. A novel, thin film slurry
      photoreactor was evaluated in this work for its effectiveness in removing phenol.
      The efficiency of parameters, initial phenol and catalyst concentrations and the
      light intensity on phenol removal was studied. The reactor performed well giving
      near complete removal of phenol even at a higher concentration of 500 mg/l.

PMID- 14672374
TI  - Destruction of cyanide in aqueous waste by electrochemical oxidation.
AB  - A laboratory study was carried out by electrochemical oxidation to destroy
      cyanide in aqueous waste. The electrode used in this study was a triple oxide
      coated titanium based mesh type anode and a carbon cathode. Direct and indirect
      methods were both carried out at alkaline conditions and indirect oxidation
      method in the presence of chloride was found to be more efficient.

PMID- 14672375
TI  - Ionic membrane technologies for the recovery of valuable chemicals from waste
      waters.
AB  - An overview of various processes is provided in which use of ionic membranes and
      related technologies (dialysis, electrodialysis, electrolysis, etc.) enable the
      recovery of valuable chemicals. The most relevant literature in the field is
      surveyed and some elucidating case studies are discussed, also accounting for the
      results of some research programmes carried out in our laboratories.

PMID- 14672376
TI  - Enhanced photocatalytic degradation of monocrotophos in aqueous solution over
      titania hybridised with beta-zeolite.
AB  - Photocatalytic degradation of monocrotophos has been carried out in a slurry type
      batch reactor. The reaction variables were optimised to obtain maximum
      degradation efficiency. The degradation rate of monocrotophos is significantly
      higher for acidic solutions than for alkaline solutions. It is also observed that
      the high concentration environment of the pollutant formed around the hybridised
      TiO2, enhances the mineralisation rate of monocrotophos. Hence an increase in
      relative photonic efficiency is obtained.

PMID- 14672378
TI  - Electrocatalytic treatment of waste: studies on discoloration of an industrial
      azo dye effluent.
AB  - A textile dye effluent containing chiefly reactive azo dyes has been treated
      electrochemically for discoloration and COD (chemical oxygen demand) reduction at
      different current densities, flow rates and dilution. Experiments have been
      carried out in a thin electrochemical reactor under single pass conditions using
      a dimensionally stable catalytic anode (DSA) and a stainless steel cathode.

PMID- 14672377
TI  - Removal of cyanides by electrooxidation.
AB  - The paper describes a study on electro-oxidation of cyanides complexed with
      copper, present in metal plating wastewater. A detailed voltammetric study has
      indicated that formation in situ of the electrocatalytic film of copper oxide and
      electro-oxidation of cyanides probably occurs at the same anode potential. By
      contrary to other materials at which electro-oxidation of cyanide also occurs, at
      copper oxide elimination of cyanide occurs at a potential lower then the
      potential of hydroxide ion discharge.

PMID- 14672379
TI  - Introduction of John P. Elder, PhD, MPH, FAAHB, Research Laureate, 2003.

PMID- 14672380
TI  - Reaching out to America's immigrants: community health advisors and health
      communication.
AB  - PURPOSE: To describe clinical services and health communication needs for recent
      immigrants. METHODS: A review of relevant health behavior and policy research
      published in the past 20 years was conducted. RESULTS: Health coverage for
      primary care, prenatal and safety net services needs to be continued for all
      immigrants. Legislative bodies should repeal those aspects of welfare reform laws
      that diminish funding for health programs. English training provides efficient
      and effective access to health care and health communication. Finally, health
      communication messages mediated by community health advisors constitute an
      effective alternative to mainstream health communication. CONCLUSIONS: Societies
      whose populations consist primarily of immigrants need to be better prepared to
      promote the health of this group.

PMID- 14672381
TI  - Health promotion dissemination and systems thinking: towards an integrative
      model.
AB  - OBJECTIVE: To help close the gap between health promotion research and practice
      by using systems thinking. METHODS: We reviewed 3 national US tobacco control
      initiatives and a project (ISIS) that had introduced systems thinking to tobacco
      control, speculating on ways in which systems thinking may add value to health
      promotion dissemination and implementation in general. RESULTS: The diversity of
      disciplines involved in tobacco control have created disconnection in the field;
      systems thinking is necessary to increase the impact of strategies. CONCLUSION:
      Systems thinking has potential to improve synthesis, translation, and
      dissemination of research findings in other health promotion initiatives.

PMID- 14672382
TI  - Studying the news on public health: how content analysis supports media advocacy.
AB  - OBJECTIVE: To describe how content analysis of the news assists media advocates.
      METHODS: A description of how findings from the Berkeley Media Studies Group's
      research on how 2 public health issues have been portrayed in the news has
      informed media advocacy. RESULTS: For media advocates, the research suggests they
      make themselves available to reporters, prepare spokespeople representing key
      stakeholders, and make data available. For reporters, the research suggests they
      expand sources beyond the "usual suspects," provide context in regular reporting,
      increase enterprise and investigative reporting, and ask better questions based
      on epidemiology and risk factors. CONCLUSION: Content analysis can help media
      advocates pinpoint areas for creating news to advance policy.

PMID- 14672383
TI  - Tailored and targeted health communication: strategies for enhancing information
      relevance.
AB  - OBJECTIVE: To discuss tailored messages in the broader context of communication
      strategies designed to enhance the relevance of health information to a given
      audience. METHODS: Describe specific mechanisms through which tailored health
      communication can enhance message relevance and identify situations in which the
      use of tailoring is most appropriate. RESULTS: Overall, tailored messages appear
      to stimulate greater cognitive activity than do messages that are not tailored.
      However, non-tailored messages that happen to be a good fit for a given
      individual also have similar effects. CONCLUSION: Health communication programs
      and materials that succeed in making information relevant to their intended
      audience will be more effective than those that do not. Tailoring is a proven
      approach to enhancing message relevance, but not the only approach to do so, and
      under many circumstances may not be the preferred choice.

PMID- 14672384
TI  - Mass media strategies targeting high sensation seekers: what works and why.
AB  - OBJECTIVES: To examine strategies for using the mass media effectively in drug
      prevention campaigns targeting high sensation seekers. METHODS: Both experimental
      lab and field studies were used to develop a comprehensive audience segmentation
      strategy targeting high sensation seekers. RESULTS: A 4-pronged targeting
      strategy employed in an antimarijuana media campaign yielded significant drops in
      30-day marijuana use by adolescents. Other research demonstrates how high and low
      sensation seekers process antidrug ads differently. CONCLUSIONS: Mass mediated
      anti-drug campaigns aimed at high sensation seekers are effective tools for drug
      prevention.

PMID- 14672385
TI  - The role of professional societies in promoting integrity in research.
AB  - OBJECTIVES: To summarize what is known about and to offer suggestions for steps
      professional societies can take to foster greater integrity in research. METHODS:
      Analysis of research literature on research integrity. RESULTS: Research on
      research integrity has identified 3 areas for concerns about integrity: 1)
      research misconduct, 2) questionable research practices, and 3) the research
      environment. CONCLUSIONS: It is suggested that professional societies should 1)
      undertake a careful assessment of needs and possible problems in their research
      areas, 2) develop resources to address specific problems, and 3) take more active
      roles in promoting integrity in research among their members.

PMID- 14672386
TI  - Informed-consent issues with adolescent health behavior research.
AB  - OBJECTIVE: To identify the informed-consent issues when conducting adolescent
      health behavior research. METHODS: A literature review was conducted across
      diverse academic fields about the informed-consent issues that were relevant to
      adolescent health behavior research. RESULTS: Issues included defining consent,
      assent and permission, minimal risk, risk assessment; legal issues; adolescent
      capacity to participate in research, and parental permission. CONCLUSIONS:
      Integrity in research means doing the right thing. Obtaining adolescent informed
      consent must be obtained every time data are collected. There seem to be
      occasions in which waiver of parental permission in some adolescent health
      behavior research is warranted.

PMID- 14672387
TI  - Conducting cognitive interviews to understand question-response limitations.
AB  - OBJECTIVES: To illustrate how cognitive interviewing techniques can be used to
      identify question-response problems for poorer and less educated survey
      respondents and to describe how qualitative analyses of interviews can improve
      survey questionnaires. METHODS: A cognitive interviewing project testing a
      general health questionnaire was administered in southern rural Mississippi.
      RESULTS: Three themes of response difficulty were identified: 1) responding
      within a survey interaction, 2) making mathematical calculations, and 3)
      responding within another system of knowledge. CONCLUSION: Understanding how
      sociocultural factors impact the response process is vital for survey research.

PMID- 14672388
TI  - American Academy of Health Behavior: a journey and an adventure--incoming
      presidential address.

PMID- 14672389
TI  - Ethnicity and the theory of planned behavior in the exercise domain.
AB  - OBJECTIVE: To examine the moderating influence of ethnicity on the theory of
      planned behavior (TPB) in the exercise domain and to generate common and ethnic
      specific underlying accessible beliefs. METHODS: 90 Caucasian and 94 African
      American undergraduate students completed a TPB questionnaire. RESULTS:
      Multilevel modeling analyses indicated that ethnicity and gender interacted by
      moderating the relationships between exercise intention and effective (beta = 
      0.44) and instrumental (betaeta = 0.39) attitudes. Furthermore, common and ethnic
      specific underlying accessible beliefs were identified. CONCLUSION: When exercise
      interventions are developed, ethnicity and gender may need to be considered when
      dealing with affective and instrumental attitudes.

PMID- 14672390
TI  - Psychosocial predictors of increased smoking stage among sixth graders.
AB  - OBJECTIVES: To identify predictors of increases in smoking stage among sixth
      graders. METHODS: At the beginning and end of sixth grade, 973 students completed
      surveys. Multivariate, partial proportional odds analyses were conducted.
      RESULTS: Time 1 intenders were 4 times more likely than never users to smoke at
      Time 2. In adjusted analyses, female sex, white race, peers, and perceived
      prevalence were positively associated with an increase in smoking stage, and
      social competence, parental expectations, and parental monitoring were negatively
      associated with an increase in smoking stage. CONCLUSIONS: Early adolescent
      smoking advanced in stages; intent predicted initiation; peer and parent
      influences were independently associated with increases in smoking stage.

PMID- 14672391
TI  - The risk of offending on homicide victimization: a public health concern.
AB  - OBJECTIVE: To determine whether criminal offending increases an individual's risk
      of becoming a homicide victim. METHODS: A case-control design was used to compare
      the arrest and demographic attributes of 105 homicide victims to 105 nonvictims.
      Bi- and multivariate logistic regression models were used to determine
      differences between the two groups. RESULTS: Significant differences were found
      between homicide victims and nonvictims using different measures of arrest.
      CONCLUSIONS: The field of public health needs to take a greater interest in
      preventing violence, and by recognizing criminal offending as a risk factor to
      subsequent victimization, it can attempt to reduce fatal encounters.

PMID- 14672392
TI  - Effect of response scales on self-reported exercise frequency.
AB  - OBJECTIVES: To determine the effects of 5 different numerical response scales-
      continuous-open, dichotomous-yes/no, and continuous-closed numerical (CCN) with 3
      different ranges of response frequencies (low, medium, high)--on the proportion
      of respondents defined as regular exercisers. METHODS: We randomly assigned 500
      undergraduate students to complete 1 of the 5 numerical response scales. RESULTS:
      The percentage of participants defined as regular exercisers ranged from 14% in
      the CCN low-frequency group to 45% in the CCN high-frequency group [chi2 (4, 500)
      = 28.90; P<.001]. CONCLUSIONS: The different numerical response scales have a
      significant impact on the estimated percentage of regular exercisers.

PMID- 14672393
TI  - Gender and attitudes toward nutrition in prospective physicians.
AB  - OBJECTIVES: To examine gender differences in attitudes towards nutrition therapy
      within first- and fourth-year medical students. METHODS: Participants (n = 128)
      completed a computer self-administered questionnaire assessing attitudes towards
      nutrition therapy. RESULTS: Analysis of covariance revealed that females report
      significantly more positive attitudes toward nutrition than males do, controlling
      for age. The magnitude of the difference was the same in beginning and graduating
      medical students. CONCLUSIONS: Gender differences in attitudes towards nutrition
      are not moderated by medical school socialization. Standardized nutrition
      education may be required to address disparities in knowledge, attitudes, and
      efficacy with regard to nutrition and preventive care measures.

PMID- 14672394
TI  - Adolescent suicidality and adult support: the reach for health study of urban
      youth.
AB  - OBJECTIVE: To examine suicidality among urban youth and its relationship to
      patterns of adult support. METHODS: Study surveyed 879 adolescents. Suicide
      ideation and attempts, perceived adult support, family and formal network
      availability, and network activation were assessed. RESULTS: Only half of those
      reporting a suicide attempt had spoken with an adult about their distress.
      Suicide attempters were more likely than nonattempters to report they would not
      go to family members in the future, although they were more likely to report a
      past discussion. CONCLUSION: Improving communication among youth, families, and
      service providers should be a focus of suicide prevention planning.

PMID- 14672395
TI  - The transtheoretical model: gender differences across 3 health behaviors.
AB  - OBJECTIVE: To investigate gender differences in stage-of-change distribution,
      self-efficacy, and decisional balance, for 3 health behaviors. METHODS: Five
      hundred fifty-four (males = 107; females = 447) low-income, predominantly African
      American, patients completed stage-of- change, self-efficacy, and decisional
      balance scales for smoking cessation, exercise adoption, and dietary fat
      reduction. RESULTS: Males and females differ in stage of change for smoking and
      exercise, but not dietary fat intake. CONCLUSIONS: Gender-specific interventions
      may be needed to promote certain health behaviors but not others, and self
      efficacy and decisional balance may be related differently to stage of change in
      low-income populations.

PMID- 14672396
TI  - ViewPoint: conversation with Elbert D. Glover. Interview by Molly T. Laflin and
      David R. Black.

PMID- 14672397
TI  - p53 inactivation is a rare event in familial breast tumors negative for BRCA1 and
      BRCA2 mutations.
AB  - Germline mutations at BRCA1 or BRCA2 genes result in susceptibility to breast and
      ovarian cancers. BRCA1- and BRCA2-associated tumors have distinct histologic and
      molecular phenotypes, as compared to sporadic breast tumors. Typically, a higher
      grade of malignancy is observed in BRCA-associated cancers. A number of studies
      have suggested that BRCA1 and BRCA2 proteins are of importance in DNA repair and
      maintenance of genome integrity, bringing about molecular models of tumor
      pathogenesis. In particular, alterations at p53 gene have been suggested to be a
      necessary step in the tumorigenesis of BRCA-associated carcinomas. In fact, BRCA
      associated breast cancers have higher p53 mutation frequencies than sporadic
      ones. At present, very little is known regarding BRCA non-associated familial
      tumors (termed BRCAx tumors). To our knowledge no data is available on p53
      alterations in this sub-group of familial tumors. In this study p53 alteration
      frequencies were evaluated in 13 BRCA1, 11 BRCA2 and 55 BRCAx breast tumors.
      Tumor samples were analyzed for p53 gene mutations by PCR-SSCP/direct sequencing,
      and for p53 protein overexpression by immunohistochemistry (IHC). Altogether, p53
      alterations were detected in 54% of BRCAI tumors compared with 5% of BRCAx
      tumors. No p53 alteration was found in BRCA2 tumors. While loss of p53 checkpoint
      control is likely to be an important step in the molecular pathogenesis of BRCA1
      associated cancers, our data seem to indicate a p53-independent molecular
      mechanism underlying BRCAx neoplastic transformation.

PMID- 14672398
TI  - E2F1 expression is related with the poor survival of lymph node-positive breast
      cancer patients treated with fluorouracil, doxorubicin and cyclophosphamide.
AB  - The expressions of E2F1 and retinoblastoma protein (pRB) were analyzed in 165
      lymph node-positive breast cancers. All patients underwent adjuvant chemotherapy
      with fluorouracil, doxorubicin and cyclophosphamide (FAC). E2F1 was expressed in
      43.6% and pRB was expressed in 46.1%. E2F1 expression was significantly increased
      in pRB-expressing tumors and was associated with an S-phase fraction. By
      univariate survival analyses, E2F1 expression and ER were identified as
      significant prognostic factors for disease recurrence and patient survival. E2F1
      was the only significant prognostic factor of patient outcome after FAC
      chemotherapy by multivariate analysis.

PMID- 14672399
TI  - Familial breast cancer: scope for more susceptibility genes?
AB  - PURPOSE: The familial risk of female breast cancer is somewhat less than 2.0 when
      a first-degree relative is diagnosed with breast cancer, but it is not known to
      what extent heritable or environmental factors explain the familial clustering.
      Such data would be valuable for prevention and gene identification strategies.
      EXPERIMENTAL DESIGN: We used the nation-wide Swedish Family-Cancer Database on
      10.2 million individuals and 190,000 mothers' and 26,000 daughters' breast
      cancers to calculate familial standardised incidence ratios (SIRs), for all
      invasive breast cancers in daughters, who were 0-66 years old. Over 5500 familial
      breast cancers were recorded. RESULTS: The familial SIR for all invasive breast
      cancer was 1.71 by breast cancer in the mother only, 1.95 by breast cancer in a
      sister only, and 2.75 by breast cancer in both a mother and sister. The SIRs did
      not change when adjustments were done for period, age at first birth, parity,
      socio-economic status and region. Age difference between sisters showed a small
      variation in risk for breast cancer but the highest SIR was found for those whose
      age difference was from 6 to 10 years. Half sisters showed an excess of familial
      risks exactly half of full sisters, the SIR being 1.44. CONCLUSIONS: These data
      suggest that familial aggregation of breast cancer is mainly due to heritable
      causes. Because the known susceptibility genes only explain about a quarter of
      the familial aggregation, the remaining majority offers a challenge to new
      genomic approaches.

PMID- 14672400
TI  - Analysis of HER2 and HER4 in human myocardium to clarify the cardiotoxicity of
      trastuzumab (Herceptin).
AB  - PURPOSE: When combined with anthracyclines, the humanized anti-HER2 monoclonal
      antibody trastuzumab (Herceptin) provides significant clinical benefit for women
      with HER2-overexpressing metastatic breast cancer. However, its use is limited by
      severe cardiotoxicity. To clarify whether myocardial HER2 and HER4 expression in
      response to anthracycline exposure and cardiac damage contributes to
      cardiotoxicity, we assessed expression of HER2 and HER4 in pathologically altered
      myocardium. EXPERIMENTAL DESIGN: Cardiac biopsies from 60 patients with severe
      heart disease and cardiac tissue from 35 patients with breast cancer were
      obtained. Twenty-five of the patients with breast cancer had previously received
      anthracyclines. Three of 10 anthracycline-naive patients with breast cancer had
      received trastuzumab. Expression of HER2 and HER4 was analyzed
      immunohistochemically (HER2: HercepTest/A0485 (Dako), Cy3 detection (Dianova);
      HER4: Ab-4 (NeoMarkers)). FISH analysis (Ventana) was used to assess HER2 gene
      amplification. RESULTS: Immunohistochemistry revealed weak HER2 membrane staining
      in six cardiac biopsies, appearing as dotted staining of the whole cell membrane
      and intensified HER2 signal using fluorescent Cy3 labeling. No HER2 membrane
      staining was detected in the remaining 54 cardiac biopsies or in the myocardium
      of the 35 patients with breast cancer. HER2 gene amplification was not observed.
      All specimens showed the mild cytoplasmatic HER4 staining of normal myocardium.
      No strong HER4 expression was detected. CONCLUSIONS: Cardiac alterations are not
      associated with an strong increase in HER2 and HER4 levels. IHC detects potential
      low-level HER2 expression in some samples. However, a more sensitive technique
      may be needed for studies of the role of HER2 in cardiac tissue. These data do
      not exclude a role for inhibition of cardiac HER2 expression by trastuzumab in
      the onset of heart failure in trastuzumab-treated patients.

PMID- 14672401
TI  - Perioperative screening for metastatic disease is not indicated in patients with
      primary breast cancer and no clinical signs of tumor spread.
AB  - BACKGROUND: Is a perioperative metastatic screening program indicated in patients
      presenting with primary operable breast cancer and no signs of distant
      metastases? PATIENTS AND METHODS: The impact of staging results (chest X-ray,
      bone scanning, liver ultrasound) for prognosis, treatment, quality of life and
      costs was retrospectively analyzed in 1076 patients with an operable breast
      cancer and no clinical signs of metastases. RESULTS: Staging examinations
      revealed 30 (2.8%) distant metastases, 130 (12.1%) suspect findings and excluded
      metastases in 916 (85.1%) patients. Further diagnostic procedures confirmed
      distant metastases in 7 (5.4%) and excluded them in 123 (94.6%) out of 130
      patients with suspect findings. Distant metastases were detected more frequently
      with increasing pathological tumor size (pT < or = 2.0 cm: 1.6%, pT 2.1-5.0 cm:
      3.0%, respectively pT > 5.0 cm: 15.1%; p < 0.001) and increasing number of
      involved axillary lymph nodes (pN0: 1.9%, pN1-3+: 1.8%, pN4-9+: 4.0%, pN > or =
      10+: 18.7%; p < 0.001). Due to false positive findings 123 (11.4%) patients had
      to live for a significant period of time with the psychological distress of
      suspected metastatic disease. The abandonment of a perioperative screening in
      1076 patients saves costs of at least Euros 259,367.68. CONCLUSIONS: In breast
      cancer patients without clinical signs of tumor spread perioperative screening
      for metastases is not warranted because of low frequency of metastases, false
      positive findings, missing therapeutic consequences and high costs.

PMID- 14672402
TI  - Predictive factors for the status of non-sentinel nodes in breast cancer patients
      with tumor positive sentinel nodes.
AB  - In patients with tumor positive sentinel nodes, axillary lymph node dissection is
      routinely performed while a majority of these patients have no tumor involvement
      in the non-sentinel nodes. The authors tried to identify a subgroup of patients
      with a tumor positive sentinel node without non-sentinel node tumor involvement.
      In 135 consecutive patients with tumor positive sentinel nodes and axillary lymph
      node dissection performed, the incidence of non-sentinel node involvement
      according to tumor and sentinel node related factors was examined. The size of
      the sentinel node metastasis, size of primary tumor and number of tumor positive
      sentinel nodes were the three factors significantly predicting the status of the
      non-sentinel nodes. The size of the sentinel node metastasis was the strongest
      predictive factor (P < 0.0001). In a subgroup of 41 patients with a stage T1
      tumor and micrometastatic involvement in the sentinel node only 2 patients (5%)
      had non-sentinel node involvement. In patients with small primary tumors and
      micrometastatic involvement of the sentinel nodes, the chance of non-sentinel
      node involvement is small but cannot be discarded. Because the clinical relevance
      of micrometastases in lymph nodes is still unclear it is not advisable to omit
      axillary lymph node dissection even in these patients.

PMID- 14672403
TI  - Keeping data continuous when analyzing the prognostic impact of a tumor marker:
      an example with cathepsin D in breast cancer.
AB  - The prognostic value of cathepsin D has been recently recognized, but as many
      quantitative tumor markers, its clinical use remains unclear partly because of
      methodological issues in defining cut-off values. Guidelines have been proposed
      for analyzing quantitative prognostic factors, underlining the need for keeping
      data continuous, instead of categorizing them. Flexible approaches, parametric
      and non-parametric, have been proposed in order to improve the knowledge of the
      functional form relating a continuous factor to the risk. We studied the
      prognostic value of cathepsin D in a retrospective hospital cohort of 771
      patients with breast cancer, and focused our overall survival analysis, based on
      the Cox regression, on two flexible approaches: smoothing splines and fractional
      polynomials. We also determined a cut-off value from the maximum likelihood
      estimate of a threshold model. These different approaches complemented each other
      for (1) identifying the functional form relating cathepsin D to the risk, and
      obtaining a cut-off value and (2) optimizing the adjustment for complex covariate
      like age at diagnosis in the final multivariate Cox model. We found a significant
      increase in the death rate, reaching 70% with a doubling of the level of
      cathepsin D, after the threshold of 37.5 pmol mg(-1). The proper prognostic
      impact of this marker could be confirmed and a methodology providing appropriate
      ways to use markers in clinical practice was proposed.

PMID- 14672404
TI  - Phase I trial of uracil-ftorafur, leucovorin, and etoposide: an active all-oral
      regimen for metastatic breast cancer.
AB  - PURPOSE: To determine the maximum tolerated doses, toxicities, and therapeutic
      effect of an oral chemotherapy regimen consisting of uracil-ftorafur, etoposide,
      and leucovorin for metastatic breast cancer. PATIENTS AND METHODS: The regimen
      consists of 28-day cycles of uracil-ftorafur, etoposide, and leucovorin
      administered orally on days 1-14. The dose of etoposide was fixed at 50
      mg/m2/day, and uracil-ftorafur was escalated in 50 mg/m2/day increments from 200
      to 350 mg/m2. Leucovorin, was used at a dose of 90 mg/day. Eligibility criteria
      required prior treatment with a taxane or anthracycline. RESULTS: A total of 23
      patients were enrolled. Twenty patients are assessable for toxicity and 16
      patients are assessable for response. All non-hematologic toxicities were grade 1
      or 2. Three hematologic dose-limiting toxicities (DLTs) were observed. Partial
      responses were seen in 6 of 16 (37.5%, 95% confidence interval 15%, 85%) of
      assessable patients with durations ranging from 4 to 20 months. Stable disease
      was observed in 4 of 16 (25%) of patients with durations from 4 to 12 months.
      Median time to progression was 10.5 months. An intent to treat analysis revealed
      a response of 26%. CONCLUSION: The recommended dose and schedule of this
      combination is uracil-ftorafur 350 mg/m2, leucovorin 90 mg/day, and etoposide 50
      mg/m2 for two consecutive weeks in a 4-week cycle. This all-oral regimen is well
      tolerated and demonstrates encouraging efficacy in a cohort of heavily pretreated
      patient with metastatic breast cancer.

PMID- 14672405
TI  - Combination of a zinc finger and homeodomain required for protein-interaction.
AB  - The Zinc Finger Homeodomain Enhancer-binding Protein (Zfhep) is involved in
      skeletal patterning, immune cell, muscle, and brain development, and is necessary
      for life. Zfhep contains a single central homeodomain (HD) adjacent to an
      isolated zinc finger, the function of which is unknown. The placement of a zinc
      finger so close to a homeodomain is novel in nature. The aim of this work was to
      characterize the Zfhep homeodomain (HD) or the zinc finger homeodomain (ZHD),
      with respect to DNA-binding and protein-protein interactions. Glutathione-S
      transferase (GST) fusion proteins containing either just the HD or both the zinc
      finger and HD (ZHD) were expressed in E. coli. The GST fusion protein affinity
      binding assay demonstrated that Zfhep ZHD interacts specifically with the POU
      domain of the Oct-1 transcription factor. The adjacent zinc finger is required
      since Zfhep HD alone does not interact with Oct-1 POU domain. Furthermore, ZHD
      does not bind to the POU homeodomain lacking the POU specific region. These
      results demonstrate that the Zfhep zinc finger homeodomain motif functions as a
      protein-binding domain in vitro, and suggests that Zfhep may modulate the
      activity of POU domain transcription factors. However, neither the Zfhep ZHD nor
      the HD bound DNA in EMSA or selected a DNA-binding site from a pool of random
      oligonucleotides. This is the first demonstration of a function for the HD region
      of Zfhep, which is the first case of a bi-partite domain requiring both a zinc
      finger and a HD for binding to protein.

PMID- 14672406
TI  - Early overexpression of Cdk4 and possible role of KRF and c-myc in chewing
      tobacco mediated oral cancer development.
AB  - Cyclin Dependent Kinase 4 (Cdk4) is known to be an oncogene and is involved in
      various cancers. It is over-expressed either by genomic amplification or by c-myc
      dependent manner. Our preliminary results indicate high expression of protein and
      mRNA as well as absence of genomic amplification in early oral cancer
      development. One transcription factor (TF) binding site has been detected from 
      281 to -298 by using DNase I foot printing and confirmed by electrophoretic
      mobility shift assay. This is a novel DNA sequence. The recruitment of this new
      TF as well as the earlier reported c-myc was analyzed in various stage of oral
      cancer development. The binding activity of the new TF is present in normal
      tissues and observed more in initial stage samples whereas c-myc expression was
      absent in normal and more in higher stage of oral cancer development. On the
      basis of these findings we propose the new TF to be a possible CdK4 Regulating
      Factor (KRF). This might maintain the basal level transcription in normal and
      activates Cdk4 transcription in the initial stage, where as the same role is
      carried by c-myc in higher stage of chewing tobacco mediated oral cancer
      development.

PMID- 14672407
TI  - Isolation and characterization of a cDNA encoding a putative high mobility group
      (HMG)--box protein from stored mRNA in resting cysts of the ciliate Oxytricha
      (Sterkiella) nova: ciliate macronuclear gene encoding a putative HMG-box protein.
AB  - We have isolated an cDNA after applying a DDRT-PCR analysis on mRNA from mature
      resting cysts of the ciliate Oxytricha (Sterkiella) nova. From this cDNA fragment
      the complete macronuclear minichromosome was obtained by using the Mac-End-PCR
      method. After cloning and sequencing, this cDNA shown certain similarity to HMG
      like proteins. The analysis of the inferred amino acid sequence shown that this
      putative HMG-like protein has one HMG-box interrupted by a intron. The analysis
      of others characteristics (including a 3D model) confirms that it is a HMGB
      family protein. It is the first time that a macronuclear gene encoding a putative
      HMG-box protein is isolated from resting cysts of a stichotrich ciliate. The
      possible implications of this stored mRNA in the ciliate cryptobiotic stage are
      discussed.

PMID- 14672408
TI  - Molecular cloning and characterization of rice 6-phosphogluconate dehydrogenase
      gene that is up-regulated by salt stress.
AB  - The pentose phosphate pathway (PPP) is the important metabolism pathway in plant.
      In the present study, a cDNA encoding one of the key enzymes of PPP, 6
      phosphogluconate dehydrogenase(6PGDH), was isolated from rice and designated as
      Os6PGDH. The Os6PGDH encoding protein is a cytosolic isoenzyme according to the
      absence of plastid transit peptide at the N-terminus. The full-length cDNA of
      1751 bp encodes 480 amino acids and its putative protein sequence is 94%, 84% and
      83% identical to maize, spinach and alfalfa 6PGDHs respectively. Comparison of
      the cloned mRNA sequence with that of the genomic sequence from the Rice Genome
      Project showed a simple genomic organization devoid of introns in the translated
      region of the gene. RT-PCR experiments revealed that Os6PGDH expression was high
      in inflorescence, low in root and embryos but almost absent in leaves.
      Furthermore, Os6PGDH was up-regulated in the shoots under salt stress. It is
      suggested that 6PGDH in plant may play an important role in cell division and
      salt response.

PMID- 14672409
TI  - Molecular cloning and characterization of four isoforms of mCKLF, mouse
      homologues of human chemokine-like factor.
AB  - Chemokine-like factor1 (CKLF1), and its three isoforms (CKLF2, 3 and 4), are
      recently identified human cytokines. CKLF1 is a potent chemoattractant for human
      leukocytes and can stimulate inflammation and the regeneration of murine skeletal
      muscle. CKLF2 can promote proliferation and differentiation of C2C12 muscle cells
      directly by inducing expression of myogenin and activating transcription factors.
      In the present study, we cloned CKLF murine homologues, and based on their
      biological and structural features, named them murine chemokine-like factor 2, 4,
      5 and 6 (mCKLF2, 4, 5 and 6). mCKLF2, 4, 5 and 6 encode 152, 120, 122 and 86
      amino-acid proteins, respectively. mCKLFs map to mouse chromosome 8 and have high
      sequence similarity to human CKLFs. Compared to human CKLFs, which have a CC
      motif in the C-terminal region, mCKLF2 and 4 contain a CX3C motif. Using a PCR
      based approach, it appeared mCKLF2 and 5 mRNA were highly expressed in adult
      testis, while mCKLF4 mRNA was detected only in differentiated C2C12 cells, a
      pattern different from human CKLFs. Conditioned media from COS-7 cells
      transfected with mCKLF2 and 4 was chemotactic for mouse neutrophils, macrophages
      and lymphocytes. Our results show that mCKLF2, 4, 5 and 6 are four splicing
      variants which are homologues of human CKLFs and murine CKLFs possess distinct
      features compared to their human counterparts.

PMID- 14672410
TI  - Characterization of a novel splicing variant of KLHL5, a member of the kelch
      protein family.
AB  - The kelch-repeat protein family is a recently found new kind of actin-binding
      protein. It is characterized by tandemly arranged motifs of about 50 amino acids.
      Previous study showed that most members of the kelch-repeat family were
      cytoskeletal proteins implicated in various cellular processes, such as actin
      cytoskeleton interaction, cytoplasmic sequestration of transcription factors and
      cell morphology. And some of the family members play important roles in tissue
      development, such as human ENC-1, NRP/B, etc. Another characteristic of the kelch
      family is that most members have another conserved BTB domain at the extreme
      amino terminus. The BTB domain is also found at the N-terminus of 5-10% of zinc
      finger transcription factor types and is a conserved protein-protein interaction
      motif. During the large-scale sequencing analysis of a human fetal brain cDNA
      library we found a novel kelch-like protein gene 5, KLHL5, KLHL5 has high
      identity with Drosophila kelch protein and many other family members. Here we
      report a novel splicing variants of KLHL5, named KLHL5b and the expression
      pattern of KLHL5b in many tissues.

PMID- 14672411
TI  - Characterization of the tissue-specific expression of the s100P gene which
      encodes an EF-hand Ca2+-binding protein.
AB  - S100 proteins are a calcium-binding protein family containing two EF-hand domains
      exclusively expressed in vertebrates and play roles in many cellular activities.
      Human S100P gene was first cloned as a 439 bp cDNA in placenta and it was found
      to be associated with human prostate cancer. Here we describe the cloning of the
      1297 bp full-length cDNA, and the characterization of the tissue-specific
      expression of the human S100P gene. It is abundantly expressed in many tissues
      including placenta by Northern blot and RT-PCR analysis, unlike the expression
      pattern of other S100 family genes.

PMID- 14672412
TI  - GADD45gamma, down-regulated in 65% hepatocellular carcinoma (HCC) from 23 chinese
      patients, inhibits cell growth and induces cell cycle G2/M arrest for hepatoma
      Hep-G2 cell lines.
AB  - Growth-arrest and DNA-damage inducible (GADD) genes and Myeloid differentiation
      primary response (MyD) genes represent a family of genes that play a key role in
      negative control of cell growth. In the present study, following clone and
      location of human GADD45 gamma (MyDL) gene, we have found that its mRNA
      expression level was down-regulated in 15/23 cases of clinic hepatocellular
      carcinoma (HCC) by comparing the northern hybridization results between the tumor
      tissues and adjacent normal tissues. Transient transfection of GADD45 gamma cDNA
      with intact open reading frame sequence into the human hepatoma cells Hep-G2
      resulted in dramatic growth suppression in colony formation assays. Furthermore,
      flow cytometry analysis indicated that GADD45 y caused cell cycle arrest at G2/M
      transition when transfected into Hep-G2 cells. Therefore, the possible role of
      GADD45 gamma in cell growth control was further confirmed in this paper.

PMID- 14672413
TI  - Cloning and characterization of the human IFT20 gene.
AB  - Intraflagellar transport (IFT), in which molecular motors and IFT particle
      proteins participate, is very important in assembling and maintaining many
      cilia/flagella, such as the motile cilia that drive the swimming of cells and
      embryos, the nodal cilia that generate left-right asymmetry in vertebrate
      embryos, and the sensory cilia that detect sensory stimuli in some animals. Here
      we report the molecular cloning and characterization of a novel human cDNA that
      is 1060 base pair in length, encoding a putative protein of 158 amino acid
      residues which shares high homology to Mus musculus intraflagellar transport
      protein mIFT20 (Accession number AAL99202, identity 82.3%, similarity 82.9%) at
      protein level. Bioinformatics analysis revealed that the gene is composed of 6
      exons and is located on human chromosome 17p 11.1. RT-PCR showed that this gene
      is expressed in human brain, lung, kidney and pancreas, and lower expression were
      also detected in human placenta, liver, thymus, prostate and testis.

PMID- 14672414
TI  - Bioartificial organ grafts: a view at the beginning of the third millennium.
AB  - An immunoisolated collection of cells, which communicate and exchange essential
      factors, co-stimulatory hormones, as well as providing immunoprotection and
      immunomodulation, can be prepared, given existing scientific and medical know
      how, within two decades. These "Bioartificial Organ Grafts" have advantages
      relative to isolated cell therapies, including beta-cell encapsulation for
      diabetes treatment, and xenotransplantation, which has a de facto moratorium.
      This paper documents that the majority of the research for the bioartificial
      organ grafts has been concluded, with the remaining hurdles minimum in
      comparison. The use of co-encapsulation and the induction of local immune
      privilege will provide a more sensitive humoral hormonal response and graft
      survival, without systemic immunosuppression. A call for the staged
      implementation of bioartificial organ grafts, based on the best available medical
      practice, materials, tissue and technology available, is advocated. The
      implementation of bioartificial organ grafts can begin within the next two years,
      based on allografts succeeded by genetically modified human tissue, without the
      need to pass through a xenograft stage.

PMID- 14672415
TI  - Biocompatibility of alginates for grafting: impact of alginate molecular weight.
AB  - Optimising microencapsulation technology towards the effective clinical
      transplantation has created the need for highly biocompatible alginates.
      Therefore, in this study the biocompatibility of different beads prepared from
      alginates with varying average molecular weight was examined. In some experiments
      the beads were covered with a multilayer membrane surrounded by an alginate
      layer. First of all, we found that beads made of a lower weight average alginate
      elicted a much stronger fibrotic response compared to beads made of a higher
      weight average alginate (LV-alginate > MV-alginate). The results were confirmed
      by the observation that the extent of tissue fibrosis was significantly increased
      in multilayer capsules made of an alginate with a lower weight average (core and
      surface LV-alginate, Mw 0.7-1 * 10(6) g/mol, viscosity of a 0.1% solution 1-2.5
      mPa s(-1)) compared to multilayer capsules made of an alginate with a higher
      weight average (core and surface MV-alginate; Mw 1.2-1.3 * 10(6) g/mol, viscosity
      of a 0.1% solution 5-7 mPa s(-1)). It should be stressed, that the pro-fibrotic
      effect of the LV-alginate alginate in the core was only partially reversed by a
      MV-alginate on the surface of the multilayer capsules. On the basis of the raised
      data, it can be assumed that the molecular weight average of the alginates have
      an decisive effect on the biocompatibility. Therefore, it seems to be
      recommendable to reduce the low molecular weight fractions of the alginate during
      the purification process to improve the biocompatibility.

PMID- 14672416
TI  - Liposomes and blood cells: a flow cytometric study.
AB  - To clarify the interactions of liposomes with blood cells, this study examined
      the behaviour of liposomes of a range of compositions in the presence of purified
      human blood cells in buffer or plasma; or in whole blood, or in mice in vivo.
      Liposomes, labeled with the hydrophilic fluorochrome, carboxy fluorescein (CF),
      or with membrane-sequestering R18 or FITC-labeled phospholipids, were mixed with
      blood cells and the appearance of the fluorochromes in the blood cell population
      was monitored by flow cytometry. Irrespective of composition, with or without
      poly(ethylene glycol), all types of liposomes were found to interact rapidly and
      dose-dependently with red cells, leukocytes and platelets, both in vitro and in
      vivo. This took place equally in the presence and the absence of plasma proteins
      and functional enzyme cascades, suggesting that the prime facie interaction is
      opsonization-independent and is consistent with liposome-blood cell fusion.

PMID- 14672417
TI  - Free and microencapsulated Lactobacillus and effects of metabolic induction on
      urea removal.
AB  - We have previously reported the experimental use of genetically engineered
      Escherichia coli with microencapsulation to lower nitrogenous waste. Concern has
      surfaced, nonetheless, about safety of genetically engineered product. The
      purpose of this study is to explore the alternative use of probiotics in removal
      of plasma urea. After repeated cycles of exposure of Lactobacillus delbrueckii in
      urea-rich medium under anaerobic environment, the organisms were demonstrated to
      lower plasma urea concentration in vitro. Suspension of Lactobacillus in uremic
      plasma reduced the urea nitrogen levels from 51.5 +/- 5.2 mg/dL to 44.3 +/- 3.9
      mg/dL (P = 0.02) after 24 hours. With microencapsulation of Lactobacillus (inside
      semipermeable alginate-polylysine-alginate polymeric membrane), further lowering
      of urea nitrogen levels was achieved (35.4 +/- 0.8 mg/dL, P = 0.03) at 24 hours.
      These preliminary data show that expression of certain enzymes could be induced
      in Lactobacillus delbrueckii and thus capable of lowering plasma urea. Further
      studies and molecular analysis would be indicated to explore and refine the
      techniques.

PMID- 14672418
TI  - Preparation and characterization of collagen-hydroxyapatite composite used for
      bone tissue engineering scaffold.
AB  - In this study, highly porous collagen-HA scaffolds were prepared by solid-liquid
      phase separation method. Microstructure of the composites was characterized by
      SEM, TEM and XRD. The results show that collagen-HA scaffolds are porous with
      three-dimension interconnected fiber microstructure, pore sizes are 50-150
      microm, and HA particles are dispersed evenly among collagen fiber. Compared with
      pure collagen, the mechanical property of collagen-HA composite improves
      significantly. To gain further insight into cell growth throughout 3D scaffolds,
      the cell proliferation and attachment on the scaffold in vitro was investigated.
      The collagen-HA composite has good biocompatibility, and adding HA does not
      affect the histocompatibility of the scaffold materials. The porous collagen-HA
      composite is suitable as scaffold used for bone tissue engineering.

PMID- 14672419
TI  - Primary osteoblasts response to shock wave therapy using different parameters.
AB  - Over the past decade extracorporeal shock-wave therapy (ESWT) has been
      increasingly applied to orthopaedic and musculoskeletal pathologies, the aim of
      this study was to assess how the energy density of the shock waves and the number
      of impulses affect viability, differentiation and synthetic activity of
      osteoblasts. Primary sheep osteoblasts cultures were treated with ESWT with an
      electro-hydraulic shock wave generator by selecting three different energy levels
      (14-21-28 kV corresponding at 0.15-0.31-0.40 mJ/mm2) and two different total
      numbers of impulses (500, 1000) for each level. At the end of treatment, cell
      counts and viability were recorded. Cells were then cultivated for 48 hours
      starting from a concentration of 1 x 10(4) cells/ml. The biological activity and
      viability were evaluated at 24 and 48 hours after treatment. No cytodestructive
      effects were observed in Group A, while a cytodestructive effect of ESWT was seen
      in cultures receiving the highest energy treatments. The different shock wave
      treatment induced differences in MTT assays after 24 and 48 hours, in particular
      the highest level showed a detrimental effect on cell respiration at both
      experimental times as compared to the Control Group and the protein metabolism
      was generally depressed by ESWT with impulses at the highest energy level. After
      24 hours such effect further increased with the growing number of impulses. The
      lowest energy level appeared to significantly improve the metabolic parameter in
      primary cell cultures as compared to controls when 500 impulses were selected.
      The current study has demonstrated that one of the most important aspects to be
      considered is not the total number of impulses used but the energy level of the
      shock waves, thus confirming that ESWT has a dose-dependent effect on cells.

PMID- 14672420
TI  - Immobilization of phospholipase A2 on porous glass and its application for
      lowering serum cholesterol concentration.
AB  - Phospholipase A2 (PLA2; EC 3.1.1.4) is a lipolytic enzyme that hydrolysis the
      ester bond in sn-2 position of phospholipids. In this work, the PLA2 from hog
      pancreas was covalently coupled to porous glass. The properties of free and
      immobilized enzyme were also investigated and compared. The optimum pH and
      temperature were found as 8.5 and 50 degrees C, respectively for both free and
      immobilized enzyme. The immobilized enzyme had good properties that potential for
      medical application is considerable. Its use in lowering plasma cholesterol
      concentrations in blood samples was also demonstrated.

PMID- 14672421
TI  - Transient and stable transfection of Chinese hamster ovary cells with the
      recombinant feline erythropoietin gene and expression, purification, and
      biological activity of feline erythropoietin protein.
AB  - OBJECTIVE: To use transient and stable transfection of Chinese hamster ovary
      cells to clone the gene encoding feline erythropoietin (feEPO) protein,
      characterize the expressed protein, and assess its biological activity. SAMPLE
      POPULATION: Cultures of Chinese hamster ovary or TF-1 cells. PROCEDURE: The gene
      encoding feEPO was cloned into a eukaryotic expression plasmid. Chinese hamster
      ovary cells were transiently or stably transfected with the plasmid. Expressed
      recombinant feEPO (rfeEPO) protein was purified from transiently transfected
      cells. The protein was characterized by use of SDS gel electrophoresis and
      western blot analysis. Biological activity was assessed by measuring thymidine
      incorporation by TF-1 erythroleukemic cells. RESULTS: Purified rfeEPO from
      supernatants of transiently transfected cells was determined to be 34 to 40
      kilodaltons (kd) by use of SDS gel electrophoresis, whereas the molecular weight
      predicted from the amino acid sequence was 21.5 kd. The banding pattern and high
      molecular weight suggested the protein was glycosylated. The rfeEPO proteins
      derived from transient or stable transfections subsequently were determined to be
      biologically active in vitro. CONCLUSIONS AND CLINICAL RELEVANCE: The gene
      encoding feEPO can be transfected into eukaryotic cells, and the expressed rfeEPO
      protein is biologically active in vitro. Cats with chronic renal failure often
      are anemic as a result of reduced expression of erythropoietin (EPO). Treatment
      with human-derived EPO stimulates RBCs in anemic cats; however, treatment is
      often limited by the development of antibodies directed against the recombinant
      human protein, which can then cross-react with endogenous feEPO. Recombinant
      feEPO may prove beneficial for use in cats with chronic renal failure.

PMID- 14672422
TI  - Evaluation of multiple radiographic predictors of cartilage lesions in the hip
      joints of eight-month-old dogs.
AB  - OBJECTIVE: To determine the radiographic methods that best predict the
      development of osteoarthritis in the hip joints of a cohort of dogs with hip
      dysplasia and unaffected dogs. ANIMALS: 205 Labrador Retrievers, Greyhounds, and
      Labrador Retriever-Greyhound crossbred dogs. PROCEDURE: Pelvic radiography was
      performed when the dogs were 8 months old. Ventrodorsal extended-hip,
      distraction, and dorsolateral subluxation (DLS) radiographs were obtained. An
      Orthopedic Foundation for Animals-like hip score, distraction index, dorsolateral
      subluxation score, and Norberg angle were derived from examination of
      radiographs. Osteoarthritis was diagnosed at the time of necropsy in dogs > or =
      8 months of age on the basis of detection of articular cartilage lesions.
      Multiple logistic regression was used to determine the radiographic technique or
      techniques that best predicted development of osteoarthritis. RESULTS: A
      combination of 2 radiographic methods was better than any single method in
      predicting a cartilage lesion or a normal joint, but adding a third radiographic
      method did not improve that prediction. A combination of the DLS score and
      Norberg angle best predicted osteoarthritis of the hip joint or an unaffected hip
      joint. All models that excluded the DLS score were inferior to those that
      included it. CONCLUSIONS AND CLINICAL RELEVANCE: A combination of the DLS score
      and Norberg angle was the best predictor of radiographic measures in 8-month-old
      dogs to determine whether a dog would have normal or osteoarthritic hip joints.

PMID- 14672423
TI  - Effect of velocity on ground reaction forces in dogs with lameness attributable
      to tearing of the cranial cruciate ligament.
AB  - OBJECTIVE: To ascertain the effectiveness of evaluating ground reaction forces
      (GRFs) at velocities during walking and trotting in dogs with naturally occurring
      lameness and determine whether walking would provide sufficient motion to
      adequately characterize GRFs with respect to trotting. ANIMALS: 29 dogs with a
      naturally occurring tear of the cranial cruciate ligament. PROCEDURE: Dogs were
      walked and trotted over a force platform, and GRFs were recorded during the
      stance phase. Correlation was used to assess the agreement between walking and
      trotting for GRF The coefficient of variation was calculated to assess the
      relative variation of outcome variables among the gaits. Group means for walking
      GRF were compared between dogs that trotted and that failed to trot. RESULTS:
      GRFs during walking and trotting were highly correlated. The coefficient of
      variation was smaller for GRFs during walking than during trotting. Dogs that
      failed to trot had significantly smaller mean values of peak vertical force and
      vertical impulse during walking, compared with values for dogs that were able to
      trot. CONCLUSIONS AND CLINICAL RELEVANCE: Either velocity is acceptable for GRF
      evaluation in dogs. Mean GRF during walking was significantly different between
      dogs that could and could not trot, principally because dogs with the most severe
      lameness failed to trot. These dogs would be eliminated from a clinical study,
      and thus, that study would become biased toward dogs that were less lame. In that
      situation, differences between interventions may be less pronounced, because they
      would be evaluated on dogs with less lameness.

PMID- 14672424
TI  - Changes in heart rate variability in horses during immersion in warm springwater.
AB  - OBJECTIVE: To determine the effects of immersion in warm springwater (38 degrees
      to 40 degrees C) on autonomic nervous activity in horses. ANIMALS: 10 male
      Thoroughbreds. PROCEDURE: Electrocardiograms were recorded from horses for 15
      minutes during a warm springwater bath after being recorded for 15 minutes during
      stall rest. Variations in heart rate (HR) were evaluated from the power spectrum
      in terms of low frequency (LF, 0.01 to 0.07 Hz) power and high frequency (HF,
      0.07 to 0.6 Hz) power as indices of autonomic nervous activity. RESULTS: Mean (+/
      SE) HR during stall rest and immersion in warm springwater was 31.1 +/- 1.7 and
      30.3 +/- 1.0 beat/min, respectively. No significant difference was found between
      the HR recorded during stall rest and that recorded during immersion in warm
      springwater. The HF power significantly increased from 1,361 +/- 466
      milliseconds2 during stall rest to 2,344 +/- 720 milliseconds2 during immersion
      in warm springwater. The LF power during stall rest and immersion in warm
      springwater was 3,847 +/- 663 and 5,120 +/- 1,094 milliseconds2, respectively,
      and were not significantly different from each other. Similarly, the LF:HF ratio
      did not change during immersion in warm springwater. The frequency of second
      degree atrioventricular block, which was observed in 2 horses, increased during
      immersion in warm springwater, compared with during stall rest. CONCLUSIONS AND
      CLINICAL RELEVANCE: Increases in HF power indicates that the parasympathetic
      nervous activity in horses increases during immersion in warm springwater. Thus,
      immersion in warm springwater may provide a means of relaxation for horses.

PMID- 14672425
TI  - Evaluation of iohexol clearance used to estimate glomerular filtration rate in
      clinically normal foals.
AB  - OBJECTIVE: To determine whether pharmacokinetic analysis of data derived from a
      single i.v. dose of iohexol could be used to predict creatinine clearance and
      evaluate simplified methods for predicting serum clearance of iohexol with data
      derived from 2 or 3 blood samples in clinically normal foals. ANIMALS: 10 healthy
      foals. PROCEDURE: Serum disposition of iohexol and exogenous creatinine clearance
      was determined simultaneously in each foal (5 males and 5 females). A 3
      compartment model of iohexol serum disposition was selected via standard methods.
      Iohexol clearance calculated from the model was compared with creatinine
      clearance. Separate limited-sample models were created with various combinations
      of sample times from the terminal slope of the plasma versus time profile for
      iohexol. Correction factors were determined for the limited-sample models, and
      iohexol clearance calculated via each method was compared with exogenous
      creatinine clearance by use of method comparison techniques. RESULTS: Mean
      exogenous creatinine clearance was 2.17 mL/min/kg. The disposition of iohexol was
      best described by a 3-compartment open model. Mean clearance value for iohexol
      was 2.15 mL/min/kg and was not significantly different from mean creatinine
      clearance. A method for predicting serum iohexol clearance based on a 2-sample
      protocol (3- and 4-hour samples) was developed. CONCLUSIONS AND CLINICAL
      RELEVANCE: Iohexol clearance can be used to predict exogenous creatinine
      clearance and can be determined from 2 blood samples taken after i.v. injection
      of iohexol. Appropriate correction factors for adult horses and horses with
      abnormal glomerular filtration rate need to be determined.

PMID- 14672426
TI  - Effect of induced unilateral synovitis of distal intertarsal and tarsometatarsal
      joints on sagittal plane kinematics and kinetics of trotting horses.
AB  - OBJECTIVE: To study the effect of unilateral synovitis in the distal intertarsal
      and tarsometatarsal joints on locomotion, including the compensating effects
      within and between limbs. ANIMALS: 4 clinically normal horses. PROCEDURE: Gait
      analyses including kinematics, force plate, and inverse dynamic analysis were
      performed at the trot before lameness, after which synovitis was induced by
      injecting endotoxin into the right distal intertarsal and tarsometatarsal joints.
      Gait analyses were repeated 24 to 30 hours later during lameness. Differences
      between the stride variables during the 2 conditions (lame and sound) were
      identified. RESULTS: Tarsal joint range of motion, peak vertical force, and
      vertical impulse were decreased during lameness. Mechanical deficits included a
      decrease in negative work performed by the tarsal extensors during the early
      stance phase and a decrease in positive work by the tarsal extensors during push
      off. No compensatory changes in work were performed by other joints within the
      lame hind limb during the stance phase. Vertical impulse in the diagonal forelimb
      decreased, but there were no significant changes in forces or impulses in the
      ipsilateral forelimb or contralateral hind limb. CONCLUSION AND CLINICAL
      RELEVANCE: Results indicate that horses are able to manage mild, unilateral hind
      limb lameness by reducing the airborne phase of the stride rather than by
      increased loading of the compensating limbs.

PMID- 14672427
TI  - A cohort study of telomere and telomerase biology in cats.
AB  - OBJECTIVE: To investigate telomere lengths in tissues of domestic shorthair (DSH)
      cats of various ages, evaluate the relationship between telomere length and age
      of cats, and investigate telomerase activity in the somatic tissues of cats.
      SAMPLE POPULATION: Tissues obtained from 2 DSH cats and blood samples obtained
      from 30 DSH cats. PROCEDURE: DNA isolated from blood cells and somatic tissue
      samples was subjected to terminal restriction fragment (TRF) analysis to
      determine mean telomere repeat lengths. Protein samples were subjected to
      analysis by use of a telomeric repeat-amplification protocol to assess telomerase
      activity. RESULTS: MeanTRF values of cats ranged from 4.7 to 26.3 kilobase pairs,
      and there was significant telomeric attrition with increasing age of cat.
      Telomerase activity was not found in a wide range of normal tissues obtained from
      2 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of these results clearly
      indicates that telomeres are shorter in older cats, compared with young cats;
      therefore, telomeres are implicated in the aging process. The analysis of
      telomerase activity in normal somatic tissues of cats reveals a pattern of
      expression similar to that found in human tissues. IMPACT FOR HUMAN MEDICINE:
      Fundamental differences in the biological characteristics of telomeres and
      telomerase exist between humans and the other most widely studied species (ie,
      mice). The results reported here reveal similarities in telomere and telomerase
      biologic characteristics between DSH cats and humans. Hence, as well as
      developing our understanding of aging in cats, these data may be usefully
      extrapolated to aging in humans.

PMID- 14672428
TI  - Effects of exercise and glucose administration on content of insulin-sensitive
      glucose transporter in equine skeletal muscle.
AB  - OBJECTIVES: To characterize insulin-sensitive glucose-transporter (GLUT-4)
      protein in equine tissues and determine effects of exercise and glucose
      administration on content of GLUT-4 protein in equine skeletal muscle. SAMPLE
      POPULATION: Tissue samples from 9 horses. PROCEDURES: Western blot analyses were
      performed on crude membrane preparations of equine tissues to characterize GLUT
      4. In a crossover, randomized study, horses were strenuously exercised for 3
      consecutive days and then administered 13.5% glucose or isotonic saline (0.9%
      NaCl; control) solution, i.v., at similar infusion rates for 12.1 hours. Samples
      were collected from the middle gluteal muscle before and after exercise and 10.1
      hours after completion of an infusion and used for measurements of glycogen
      concentration and total content of GLUT-4 protein. RESULTS: Immunoblot analyses
      detected specifically immunoreactive bands for GLUT-4 in insulin-sensitive
      tissues. Content of GLUT-4 protein in skeletal muscle increased significantly by
      27.3 and 12.3% 22.2 hours after exercise for control and glucose groups,
      respectively. Intravenous infusion of glucose resulted in a significantly higher
      rate of glycogenesis, compared with results for the control group (mean +/- SD,
      3.98 +/- 0.61 and 1.47 +/- 0.20 mmol/kg/h, respectively). Despite enhanced
      glycogenesis, we did not detect an increase in content of GLUT-4 protein after
      glucose infusion, compared with values after exercise. CONCLUSIONS AND CLINICAL
      RELEVANCE: GLUT-4 protein was expressed in equine skeletal and cardiac muscles.
      Exercise increased total content of GLUT-4 protein in skeletal muscle, and
      replenishment of muscle glycogen stores after glucose infusion attenuated the
      exercise-induced increase in the content of GLUT-4 protein in equine skeletal
      muscle.

PMID- 14672429
TI  - Use of a multiplex polymerase chain reaction assay in the antemortem diagnosis of
      toxoplasmosis and neosporosis in the central nervous system of cats and dogs.
AB  - OBJECTIVE: To develop a multiplex polymerase chain reaction (PCR) assay for the
      detection of Toxoplasma gondii and Neospora caninum DNA in canine and feline
      biological samples. SAMPLE POPULATION; Biological samples from 7 cats with
      systemic (n = 4) or CNS (3) toxoplasmosis, 6 dogs with neospora- or toxoplasma
      associated encephalitis, and 11 animals with nonprotozoal disease. PROCEDURE:
      Primers for T gondii, N caninum, and the canine ferritin gene (dogs) or feline
      histone 3.3 gene (cats) were combined in a single PCR assay. The DNA was
      extracted from paraffin-embedded brain tissue, CSF, or skeletal muscle. The PCR
      products with positive results were cloned, and sequence identity was confirmed.
      RESULTS: Of 7 cats and 4 dogs with immunohistochemical or serologic evidence of
      toxoplasmosis, PCR results were positive for all cats and 3 dogs for T gondii,
      and positive for T gondii and N caninum for 1 dog. Another dog had negative PCR
      results for both parasites. Of 2 dogs with immunohistochemical or serologic
      evidence of neosporosis, PCR results were positive for 1 for N caninum and
      positive for the other for T gondii. All negative-control samples yielded
      negative results for T gondii and N caninum on the PCR assay. CONCLUSIONS AND
      CLINICAL RELEVANCE: Standard tests for toxoplasmosis or neosporosis associated
      with the CNS rely on serologic, histologic, or immunohistochemical analysis and
      can be difficult to interpret. The multiplex PCR assay with built-in control
      reactions could be a complementary clinical tool for the antemortem diagnosis of
      toxoplasmosis or neosporosis associated with the CNS.

PMID- 14672430
TI  - In vitro effects of Actinobacillus pleuropneumoniae on inducible nitric oxide
      synthase and cyclooxygenase-2 in porcine alveolar macrophages.
AB  - OBJECTIVE: To determine the amount of inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) activity in alveolar macrophages in response to
      Actinobacillus pleuropneumoniae (APP) by determining nitric oxide (NO) and
      prostaglandin E2 (PGE2) concentrations. SAMPLE POPULATION: Freshly isolated
      porcine alveolar macrophages. PROCEDURE: Alveolar macrophages were incubated for
      48 hours with APP (1 X 10(4) colony-forming units/mL), interleukin-1beta, (IL
      1beta; 5 U/mL), tumor necrosis factor-alpha (TNFalpha; 500 U/mL), interferon
      gamma (IFN-gamma, 100 U/mL), or lipopolysaccharide (LPS; 10 microg/mL). In a
      second experiment, alveolar macrophages were incubated with fresh medium
      (negative control), APP alone, or APP with 1 of the following: IL-1beta, TNF
      alpha, or IFN-gamma. In a third experiment, alveolar macrophages were incubated
      with fresh medium (negative control), LPS (positive control), APP alone, or APP
      with 1 of the following: an iNOS inhibitor (3.3 microM), a COX-2 inhibitor (10
      microM); or both the iNOS and COX-2 inhibitors. Supernatant was obtained at 0, 3,
      6, 9, 12, 24, and 48 hours after treatment for determination of NO and PGE2
      production. RESULTS: The addition of APP to alveolar macrophages resulted in
      significant increases in NO and PGE2 production. The addition of APP and IFN
      gamma synergistically induced NO production. Inhibition of iNOS and COX-2
      decreased NO and PGE2 production, respectively. CONCLUSIONS AND CLINICAL
      RELEVANCE: In vitro activation of alveolar macrophages by APP results in
      increased production of NO and PGE2. Nitric oxide and PGE2 production appears to
      be largely dependent on iNOS and COX-2 activity. Pharmacologic modulation of iNOS
      and COX-2 activity may represent a therapeutic target for pigs with
      pleuropneumonia.

PMID- 14672431
TI  - Identification of geographic factors associated with early spread of foot-and
      mouth disease.
AB  - OBJECTIVE: To explore whether early analysis of spatial data may result in
      identification of variables associated with epidemic spread of foot and mouth
      disease. SAMPLE POPULATION: 37 farms with infected cattle (ie, case farms)
      reported within the first 6 days of the 2001 Uruguayan foot-and-mouth disease
      epidemic. PROCEDURE: A georeferenced database was created and retrospective
      analysis was performed on case farm location in relation to farm density, cattle
      density, farm type (ie, beef vs dairy cattle production), road density, case farm
      distance to the nearest road, farm size, farm ownership, and day of infection.
      Mean or median results of 1 to 3 day versus 4 to 6 day spatial data were
      compared. Spatial-temporal associations were investigated by correlation
      analysis. RESULTS: Comparison of mean or median values between the first 3 days
      and days 4 to 6 of the epidemic and results of correlation analysis indicated a
      significant increase in road density, cattle density, and dairy cattle production
      and a significant decrease in farm size and case farm distance to the nearest
      road that developed over time. A route that linked most case farms by the
      shortest possible distance and also considered significantly associated variables
      was created. It included 86.1% of all case farms reported by 60 days into the
      epidemic. CONCLUSIONS AND CLINICAL RELEVANCE: Epidemic direction can be assessed
      on the basis of road density and other spatial variables as early as 6 days into
      an epidemic. Epidemic control areas may be more effectively identified if local
      and regional georeferenced data are considered.

PMID- 14672432
TI  - Minimum alveolar concentration measures of central nervous system activation in
      cats anesthetized with isoflurane.
AB  - OBJECTIVE: To compare the minimum alveolar concentration (MAC) of isoflurane
      required to prevent corticocerebral activation, autonomic responses, and
      purposeful movements after somatic or visceral stimulation in cats anesthetized
      with isoflurane. ANIMALS: 17 healthy spayed female cats. PROCEDURE: Bispectral
      index (BIS), autonomic parameters, and purposeful movements were monitored before
      and after somatic or visceral stimuli in cats anesthetized with isoflurane. End
      tidal (ET) isoflurane concentration was varied to determine MAC values for
      cortical arousal (MAC(BIS)), autonomic responsiveness (MAC(BAR)), and purposeful
      movement (MAC). Bispectral index values > or = 60 were considered to represent
      corticocerebral activation. RESULTS: Minimum alveolar concentration for
      purposeful movement was significantly less than MAC(BIS) and MAC(BAR) for both
      somatic and visceral stimulation. Individual MAC values for somatic stimulation
      were not significantly different from respective MAC values for visceral
      stimulation. The percentage of cats that had a BIS response > or = 60 was
      inversely related to the end-tidal isoflurane concentration. CONCLUSIONS AND
      CLINICAL RELEVANCE: Corticocerebral arousal and subcortical autonomic reflexes
      occured at isoflurane anesthetic concentrations at which reflexive or purposeful
      movements were absent. These results suggested that isoflurane had a preferential
      effect on voluntary motor output at low end-tidal isoflurane concentrations, and
      that sensory pathways, subcortical sympathetic output, and cortical
      responsiveness are less susceptible to the anesthetic effects of isoflurane.
      Bispectral index values obtained after somatic or visceral stimulation were
      sensitive for the detection of early changes in cortical excitability.

PMID- 14672433
TI  - Use of the bispectral index as a monitor of anesthetic depth in cats anesthetized
      with isoflurane.
AB  - OBJECTIVE: To determine whether the prestimulation bispectral index (BIS) value
      or relative change in BIS after noxious stimulation can be used to assess the
      depth of isoflurane anesthesia in cats. ANIMALS: 17 healthy female cats.
      PROCEDURE: Electroencephalogram (EEG) patterns and BIS values were examined in
      cats that received increasing end-tidal (ET) isoflurane concentrations.
      Subsequently, BIS values were determined before and after either a noxious
      somatic or visceral stimulus in cats that received ET isoflurane concentrations
      ranging from 1.8% to 2.4%. Electrical stimuli of the tail base and bladder
      distension to 50 cm of water were the somatic and visceral stimuli, respectively.
      RESULTS: he resting BIS at ET isoflurane concentrations from 1.4% to 1.9%
      steadily decreased concurrently with increasing degrees of EEG suppression.
      Prestimulation BIS values, however, were not related to 1.8% to 2.4% ET
      isoflurane concentrations and not useful for prediction of BIS values or
      hemodynamic and movement responses after a noxious stimulus. The poststimulation
      BIS value and the difference between mean BIS values before and after stimulation
      were inversely correlated with increasing ET isoflurane concentrations.
      Poststimulation BIS values > 60 were observed at ET isoflurane concentrations
      greater than those associated with a movement response after a stimulus.
      CONCLUSIONS AND CLINICAL RELEVANCE: The prestimulation BIS value has limited use
      in assessing anesthetic depth in cats during isoflurane anesthesia. The change in
      BIS values after a noxious somatic or visceral stimulus was a reliable measure of
      anesthetic depth and may be a useful measure of early arousal from the hypnotic
      state.

PMID- 14672434
TI  - Effect of dimethyl sulfoxide in the treatment of sheep experimentally infected
      with Ehrlichia ruminantium.
AB  - OBJECTIVE: To evaluate the clinical response of sheep experimentally infected
      with Ehrlichia ruminantium to treatment with dimethyl sulfoxide (DMSO). ANIMALS:
      32 Merino crossbred sheep. PROCEDURES: 16 sheep were infected with E ruminantium;
      8 of these were treated twice daily with a 10% solution of DMSO (1 g/kg, i.v.) in
      polyionic fluid for 3 consecutive days. Treatment was initiated 2 days after the
      onset of clinical disease. Eight uninfected control sheep were similarly treated
      with DMSO. Placebo treatments (polyionic fluid administrations) were given to 8
      infected and 8 uninfected sheep. Arterial and venous blood samples for blood gas
      and total plasma protein concentration measurements were collected daily (data
      from 5 days before until 6 days after onset of clinical disease were analyzed);
      physiologic variables and food consumption were also monitored. Gross pathologic
      findings and cytologic confirmation of the disease were recorded for the 16
      infected sheep. RESULTS: Infected sheep treated with DMSO were able to maintain
      pulmonary gas exchange and had reduced pleural effusion and plasma protein loss,
      compared with infected untreated sheep that became hypoxic. Infected treated
      sheep developed an uncompensated metabolic acidosis. Uninfected treated sheep had
      reduced appetite, whereas uninfected untreated sheep maintained normal food
      intake. CONCLUSIONS AND CLINICAL RELEVANCE: Results of DMSO treatment in sheep
      with experimentally induced heartwater disease indicated that administration of
      this agent, in combination with specific antimicrobial treatment, may be of some
      benefit in treatment of naturally occurring disease.

PMID- 14672435
TI  - Evaluation of serum concentrations of biochemical markers of bone metabolism and
      insulin-like growth factor I associated with treadmill exercise in young horses.
AB  - OBJECTIVE: To evaluate changes in serum concentrations of biochemical markers of
      bone metabolism and insulin-like growth factor I (IGF-I) associated with
      treadmill exercise in young horses. ANIMALS: 12 two-year-old Thoroughbred mares.
      PROCEDURE: During a 20-week study period, 6 horses were exercised on a treadmill
      3 times a week (exercise group) and 6 horses received walking exercise 6 days a
      week (controls). Serum concentrations or activity of biochemical markers and IGF
      I were assessed biweekly. Bone mineral density and content of the first phalanx
      were measured by dual-energy X-ray absorbiometry (DEXA) on completion of the
      study. RESULTS: Compared with values in controls, bone mineral density and
      content were higher and serum concentrations of osteocalcin (a marker of bone
      formation) and the carboxy-terminal telopeptide of type I collagen (a marker of
      bone resorption; ICTP) were lower in exercised horses. Serum concentration and
      activity of the bone formation markers carboxy-terminal propeptide of type I
      collagen and bone-specific alkaline phosphatase (BAP) were not different between
      the 2 groups. Serum IGF-I concentration was lower in the exercise group, compared
      with control values; there was a significant correlation between change in IGF-I
      values and changes in osteocalcin, ICTP, and BAP values at the end of the study.
      CONCLUSIONS AND CLINICAL RELEVANCE: Treadmill exercise over 20 weeks induced
      adaptive changes in bones of 2-year-old Thoroughbreds; training appears to
      increase bone mineral density, thereby enhancing mechanical strength of bone, but
      decreases bone turnover. Results indicated an association between changes in
      serum IGF-I concentration and bone cell activity in horses.

PMID- 14672436
TI  - The effect of rectal temperature on perianesthetic serum concentrations of
      transdermally administered fentanyl in cats anesthetized with isoflurane.
AB  - OBJECTIVES: To determine whether moderate hypothermia during 4 hours of
      anesthesia with isoflurane substantially affects serum concentrations of
      transdermally administered fentanyl in the perianesthetic period in cats.
      ANIMALS: 7 healthy mature cats. PROCEDURE: A fentanyl patch (25 microg/h) was
      applied to the shaved thorax 24 hours before induction of anesthesia. Anesthesia
      was induced at time 0. Each cat received 2 treatments in a random order.
      Treatments were isoflurane anesthesia with normothermia and isoflurane anesthesia
      with hypothermia. Cats were intubated, connected to a nonrebreathing circuit, and
      maintained at 1.3X minimum alveolar concentration for 4 hours. Cats in the
      hypothermia treatment groups were actively cooled to 35 degrees C following the
      induction of anesthesia. Serum fentanyl analysis was performed at -24, -12, 0, 1,
      2, 3, 4, 4.5, 5, 6, 7, 8, 9, 10, 12, and 24 hours. RESULTS: Mean +/- SEM serum
      fentanyl concentration (SFC) for the hypothermia treatment group (0.598 +/-
      0.3048 ng/mL) was significantly lower than the baseline concentration (1.834 +/-
      0.6393 ng/mL) at 1 hour. This significant reduction persisted for the duration of
      anesthesia for the hypothermia treatment group. Serum fentanyl concentrations
      returned to baseline values within 1 hour of the end of anesthesia, regardless of
      body temperature. CONCLUSIONS AND CLINICAL RELEVANCE: Hypothermia during inhalant
      anesthesia induced a significant reduction in SFC obtained with transdermal
      administration. The impact of this reduction in SFC on the contribution of
      transdermally administered fentanyl to any reduction in the need for inhalant
      anesthesia remains to be determined.

PMID- 14672437
TI  - Evaluation of a canine D-dimer point-of-care test kit for use in samples obtained
      from dogs with disseminated intravascular coagulation, thromboembolic disease,
      and hemorrhage.
AB  - OBJECTIVE: To evaluate a canine D-dimer point-of-care (cD-d POC) test kit for use
      in healthy dogs and dogs with disseminated intravascular coagulation (DIC),
      thromboembolic disease (TED), and hemorrhage. ANIMALS: 12 healthy dogs, 18 dogs
      with DIC, 23 dogs with TED (19 acute and 4 chronic), and 18 dogs with hemorrhage.
      PROCEDURE: The cD-d POC, canine D-dimer ELISA (cD-d ELISA), human D-dimer latex
      agglutination (hD-d LA), and fibrin degradation product (FDP) tests were
      performed on citrated plasma. RESULTS: All healthy dogs had negative cD-d POC
      test results and mean cD-d ELISA value of 0.2 U/mL. All dogs with DIC had
      positive cD-d POC test results and mean cD-d ELISA value of 44 U/mL. Dogs with
      acuteTED had a mean cD-d ELISA value of 34 U/mL, and 17 of 19 had positive cD-d
      POC test results. Mean cD-d ELISA value in dogs with hemorrhage was 14 units/mL,
      and 15 of 18 had positive cD-d POC test results. The cD-d ELISA values in dogs
      with hemorrhage were significantly higher than those of healthy dogs but lower
      than those of dogs with DIC and acute TED. The cD-d POC, cD-d ELISA, and hD-d LA
      tests were comparable in differentiating healthy dogs from dogs with DIC, acute
      TED, or hemorrhage and appeared to be superior to measurement of FDPs.
      CONCLUSIONS AND CLINICAL RELEVANCE: The cD-d POC test kit can be quickly and
      easily used and reliably detects dogs with DIC or acute TED. Positive results may
      also be seen in dogs with internal hemorrhage.

PMID- 14672438
TI  - Analysis methods for evaluating bacterial antimicrobial resistance outcomes.

PMID- 14672439
TI  - Quantitation of house dust mites and house dust mite allergens in the
      microenvironment of dogs.
AB  - OBJECTIVE: To quantitate the density of Dermatophagoides farinae and D
      pteronyssinus and concentrations of house dust mite (HDM) allergens (Der f 1, Der
      p 1, and Group 2 allergens) in the indoor microenvironment of dogs. SAMPLE
      POPULATION: 50 homes in Columbus, Ohio. PROCEDURES: In each home, samples of dust
      were collected from 3 locations in which dogs spent most time. Whenever possible,
      the species of mites collected was identified. Mite density (mites/g of dust) was
      assessed, and allergen concentrations were assayed by standardized ELISAs.
      Relative humidity and temperature in each home were monitored during a 5-day
      period. Characteristics of homes and sample sources were evaluated. RESULTS: Dust
      samples from all 50 homes contained > or = 1 HDM allergen; Der f 1 and Der p 1
      were detected in 100 and 74% of homes, respectively. Fifteen homes had HDMs;
      compared with D pteronyssinus, D farinae was found more commonly (14/15 homes)
      and at a higher density. Basements, homes without central air-conditioning, and
      dog beds that were > or = 1 year old had high HDM allergen concentrations. Homes
      with > or = 2 microg of Der f 1 or Group 2 allergens/g of dust or > or = 100
      mites/g of dust were significantly more likely to have a maximum relative
      humidity > or = 75%. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated the
      presence of HDMs and HDM allergens in the specific microenvironment of dogs in
      homes. Factors associated with high levels of exposure were identified, which may
      be associated with increased risk for sensitization and development of atopic
      diseases.

PMID- 14672440
TI  - Caring: utilizing the Watson theory to transcend culture.
AB  - The United States is increasingly becoming a multicultural pluralistic society.
      This is especially true in Florida where the present manuscript was written.
      Nurse practitioners must respond to growing diversity with competency and theory
      based practice strategies. This paper describes application of theoretical models
      of caring to a diverse population in Florida with emphasis on the Giger and
      Davidhizar model of transcultural nursing.

PMID- 14672441
TI  - The hospital manager and game theory: chess master, poker player, or cooperative
      game player?
AB  - Hospital management can be seen as a game, and doctors, nurses, and health
      maintenance organizations are its players. The astute hospital manager realizes
      the interdependence of individual career strategies and the hospital's success,
      just as players in a game are interdependent on each other. Managers familiar
      with game theory may successfully transfer that knowledge to the hospital realm.
      They may recognize patterns and calculate outcomes like chess players, bluff
      other hospitals into folding services as poker players do, and cooperate with
      their own team to maximize productivity. Knowledge of game theory may also make
      the hospital manager's job.

PMID- 14672442
TI  - Union certification elections in nursing care facilities.
AB  - This empirical study examines 387 union certification elections conducted by the
      National Labor Relations Board in nursing care facilities (North American
      Industry Classification System 623) from January 1999 to December 2001. Unions
      won 60% of the elections. Service Employees International Union was involved in
      42% of the elections. Bargaining unit size significantly impacted union victory.
      Unions had a better probability of winning elections in the northeast and midwest
      than in the south. Unlike other industries, American Federation of Labor-Congress
      of Industrial Organizations affiliated unions did not suffer a big labor image in
      nursing care facilities. Implications for union organizers and administrators of
      nursing care facilities are discussed.

PMID- 14672443
TI  - The economic impact of several hospitals on their community.
AB  - This study quantifies the value that several hospitals in a hospital system have
      on their local communities. Also included is an analysis of the types of value
      added services and resources offered by the hospitals. The hospitals are assessed
      in 3 arenas: as an employer, as a major provider of healthcare services, and as a
      contributor to the quality of life of the region through the involvement of its
      employees in community services activities. The results indicate that the
      hospital system contributes almost dollars 1.7 billion (or 6.6%) toward the
      dollars 25 billion local economy.

PMID- 14672444
TI  - Addressing the phenomenon of disruptive physician behavior.
AB  - This timely article provides current information on an age-old issue of
      disruptive physician behavior within the hospital setting. Documented in medical
      literature over 100 years ago, disruptive physician behavior has been an ongoing
      challenge to the hospital staff and the quality of patient care in the hospital.
      Covered in this article are the negative consequences of disruptive physician
      behavior and the call to respond. If allowed to go unchecked, a physician
      exhibiting disruptive behavior may threaten a hospital's image, staff morale,
      finance, and quality of care. Failure to respond undermines the leadership of the
      hospital and the trust of the community in the hospital's mission. Included in
      this article are suggestions obtained from the literature and from the author's
      experience in responding to disruptive physician behavior. Of emphasis is a
      methodology that includes supporting bylaws and policies to manage disruptive
      physician behavior.

PMID- 14672445
TI  - Responding to threats of workplace violence: the effects of culture and moral
      panic.
AB  - Healthcare organizations, like all organizations, are increasingly more concerned
      about workplace violence. This paper discusses the collision of a cultural
      context that encourages macho posturing and moral panic related to highly
      publicized violence in schools and workplaces. At issue is the need for
      healthcare organizations to react to evidence of potential workplace violence but
      not to overreact.

PMID- 14672446
TI  - The causes and consequences of conflict and violence in nursing homes: working
      toward a collaborative work culture.
AB  - Interpersonal conflict, often spiraling to violence and abuse, is one of the most
      daunting challenges facing nursing home administrators and their departmental
      heads. Mounting evidence documents how they spend an inordinate amount of time
      dealing with angry families, adversarial ombudsmen, regulators, and other hostile
      parties as well as handling the aftermath of the ubiquitous conflict between the
      residents and their direct caregivers. All this is in addition to coping with the
      normal interdepartmental and line staff forms of conflict that typify any
      organization. This paper details the special dynamics that accelerate
      dysfunctional conflict in nursing homes and presents strategies, tactics, and
      style recommendations that will help nursing home leaders build more
      collaborative work cultures to minimize the effects of dysfunctional conflict.

PMID- 14672447
TI  - Accepting leadership responsibility: preparing yourself to lead honestly,
      humanely, and effectively.
AB  - Many who enter management are ready and willing to accept the benefits of their
      positions, but not all are readily accepting of the full responsibilities of
      leadership. All too frequently, modern leadership appears self-serving, with the
      needs and desires of the leaders taking precedence over the needs of the
      followers and even the needs of the clients or customers. True leadership,
      however, should primarily benefit the followers rather than the leader. Leaders
      lead and followers follow for essentially the same reason, fulfillment of needs,
      so leaders and followers are fundamentally little different from each other.
      Every manager at every level has organizational superiors, so every leader is a
      follower as well. A true leader among managers is one who subordinates personal
      needs to the organization's needs, places employees well above self in
      importance, models appropriate behavior for employees, and functions as a
      facilitator in the employees' continuing efforts to get the necessary work done
      efficiently and effectively.

PMID- 14672448
TI  - Survey of gastric lesions and blood pepsinogen levels in pigs in Burkina Faso.
AB  - The purpose of the study was to investigate the prevalence of gastric lesions and
      to provide diagnostic values for serum pepsinogen in non-infected pigs and in
      pigs with gastric disease. In an abattoir survey, the pepsinogen concentrations
      were measured in the serum from 62 non-infected pigs, 33 pigs with gastric
      lesions and 17 pigs infected with Hyostrongylus rubidus, using a specific
      radioimmunoassay (RIA). The mean (+/- SE) pepsinogen concentrations in the serum
      of non-infected pigs, in pigs with gastric ulcers, and in pigs with a heavy H.
      rubidus infection were 630.8 +/- 39.2 ng/ml, 1084.5 +/- 166.2 ng/ml and 1095.2 +/
      102.3 ng/ml, respectively (p<0.05). Because of the higher concentrations of
      pepsinogen in the blood of pigs with gastric ulcers or parasitic infections, it
      is suggested that the measurement of serum pepsinogen by RIA may be an effective
      biochemical approach to the diagnosis of chronic gastric disorders in pigs.

PMID- 14672449
TI  - Relationship between the amount of linoleic acid in the diet and that in the
      adipose tissue of adult cats living freely in households.
AB  - The present study was carried out to ascertain whether linoleic acid intake and
      the content of this fatty acid in adipose tissue are correlated in cats. The
      linoleic acid intake, as estimated from a food intake questionnaire, was indeed
      correlated with the linoleic acid content of the abdominal body fat in 165 adult,
      female cats. A statistically significant linear correlation coefficient of 0.43
      was found between the percentage of linoleic acid in the adipose tissue and that
      in the diet. It is plausible that the observed acid content of adipose tissue of
      free-living cats may be considered to be a valid biomarker of linoleic acid
      intake that might be used in studies on diet and chronic disease.

PMID- 14672451
TI  - In vitro effects of acellular milk on the bactericidal components of caprine
      polymorphonuclear neutrophils.
AB  - The effects of acellular milk on the activity of the microbicidal cationic
      enzymes of the polymorphonuclear cells of goats were studied in an attempt to
      explain the phenomenon by which PMN functions fail in mastitis. Assays were
      undertaken on the myeloperoxidase, lysozyme and elastase activities in a
      polymorphonuclear cell (PMN) lysate, both in the presence and absence of
      acellular milk from homologous species. There was a significant decrease (p <
      0.05) in the activity of lysozyme, myeloperoxidase and elastase in the presence
      of acellular milk. Superoxide and H2O2 production following activation of caprine
      PMNs by lipopolysaccharide (LPS) was significantly reduced (p < 0.05) in the
      presence of acellular milk. Thus, the microbicidal function of PMNs is
      significantly impaired in the presence of acellular milk and this may contribute
      to the development of mastitis in dairy animals.

PMID- 14672450
TI  - Cholinesterase and phosphatase activities in adults and infective-stage larvae of
      levamisole-resistant and levamisole-susceptible isolates of Haemonchus contortus.
AB  - Cholinesterase (ChE) and acid phosphatase (AP) activities, but not alkaline
      phosphatase activities, were detected in cytosolic and membrane-bound fractions
      of adult and infective-stage larvae of levamisole-resistant and levamisole
      susceptible Haemonchus contortus. In contrast to other gastrointestinal
      nematodes, the ChE activity was higher in L3 than in adults and, in both cases,
      was mainly associated with membranes. ChE activity was inhibited by Triton X-100
      and was only detected in membrane-bound fractions when the detergent was removed.
      Differences between resistant and susceptible L3 were observed in the response to
      inhibitors (cytosolic fraction) and in the enzymatic content (membrane-bound
      fraction). Phosphatase activity was detected at acidic pH in all fractions, being
      higher in the adult than in the L3 stage. In the former, most of the enzyme was
      localized in the membrane-bound fractions, whereas in the latter it was mainly in
      cytosolic fractions. This difference could be correlated with the activity in the
      gut. In inhibition assays, a difference between cytosolic fractions from
      resistant and susceptible adults was observed in their response to 1 mmol/L
      tartaric acid.

PMID- 14672452
TI  - The intravenous xylitol tolerance test in non-lactating cattle.
AB  - Xylitol is a five-carbon sugar alcohol that is often used for treatment of
      ketosis in dairy cattle in Japan. An intravenous xylitol tolerance test (IVXTT,
      0.1 g/kg, bolus injection through the jugular vein) was performed in 4 non
      lactating cows (n = 4) and the results were compared with those of an intravenous
      glucose tolerance test (IVGTT) performed under equivalent conditions. The serum
      xylitol concentration reached a peak value (41.4+/-9.0 mg/dl) at 5 min, and then
      rapidly decreased and almost disappeared within 2 h. The C0 for xylitol was
      56.9+/-16.6 mg/dl and the t(1/2) was 8.5+/-0.9 min. The administration of xylitol
      appeared to cause similar secretion of insulin to that caused by glucose. There
      was also a reduction in the concentration of free fatty acids. It seems that
      xylitol has value for the treatment of ketosis. However, rapid administration of
      xylitol appeared to have an osmotic diuretic action and might be a cause of
      dehydration.

PMID- 14672453
TI  - Influence of dexamethasone on some cellular aspects of the immune system in cats.
AB  - In view of the frequent use of glucocorticoids in the treatment of cats, we
      studied the effect of dexamethasone on their immunological system. The phagocytic
      activity and oxidative burst of neutrophils and monocytes were evaluated by
      cytometric analysis using commercial kits and the subpopulations of lymphocytes
      were assessed. Neutrophilia and monocytosis reduced phagocytic activity, as shown
      from the number of phagocytized bacteria, and variations in the intensity of the
      oxidative burst in activated neutrophils and monocytes were observed.
      Dexamethasone also caused an increase in the number of B lymphocytes.

PMID- 14672454
TI  - A comparison of the susceptibility of growing mukota and large white pigs to
      infection with Ascaris suum.
AB  - The influence of A. suum infection on the haematology, liver-related serum
      enzymes, blood urea and live weight gain in Mukota and Large White (LW) weaner
      pigs was compared. Six pigs of each genotype were infected with a single dose of
      4000 A. suum eggs per pig and another six were not. The pigs were kept for 100
      days. Blood was collected daily for the first 7 days and also after 100 days. In
      the infected pigs, there was an increase (p<0.05) in alanine aminotransferase
      (ALT) activity in the LW but not in the Mukota pigs. Although the alkaline
      phosphatase (ALP) activity rose (p<0.05) in both infected and non-infected LW
      pigs from day 1 to day 3, the activity in the non-infected LW pigs then
      decreased, while that of the infected LW pigs remained elevated. The infected LW
      pigs had higher (p<0.05) levels of ALT, ALP and aspartate aminotransferase than
      their non-infected counterparts. Non-infected LW pigs tended to have higher
      (p<0.05) haematological parameters, daily weight gain and urea concentrations
      than infected LW pigs, but these differences were not significant. These
      preliminary findings suggest that more A. suum larvae reached the livers in the
      LW than in the Mukota pigs and that the latter may be more resistant to A. suum
      infection.

PMID- 14672455
TI  - Pulmonary hypertension induced in dogs by hypoxia at different high-altitude
      levels.
AB  - Chronic natural hypoxia at 2300 m altitude induces mild pulmonary hypertension
      (PH) in healthy dogs. The influence of more severe hypoxia on the same group of
      dogs was evaluated by re-examining such dogs at 3500 m, after they had regularly
      exercised at this altitude level for half a year. Despite severe hypoxaemia at
      3500 m (PaO2 52+/-5 mmHg), none of the dogs developed erythrocytosis, and their
      PCV at 3500 m (48% +/- 4%) did not differ from that at 2300 m (49% +/- 4%). There
      was a tendency towards an elevated systemic BP, with a significant increase in
      diastolic BP (105 +/- 13 mmHg at 3500 m versus 98 +/- 17 at 2300 m). Tricuspid
      regurgitation (TR) was detected in 7 dogs at 3500 m compared to 8 dogs at 2300 m.
      The mean TR Vmax was significantly higher at 3500 m, and all 7 dogs had systolic
      PH at 3500 m (33.6-54.8 mmHg), when PH was defined as TR Vmax > or = 2.8 m/s,
      i.e. a peak pressure gradient > 30 mmHg. Hence, in dogs, increasing altitude and
      the concomitant hypoxia result in a progressively more pronounced PH and an
      elevated systemic BP. Intermittent severe hypoxaemia of around 50 mmHg may not
      cause erythrocytosis in healthy dogs, even over a prolonged period.

PMID- 14672456
TI  - Pregnancy rate in zebu cows with two different postpartum intervals exposed to a
      two-bull rotational system.
AB  - In order to evaluate the reproductive effect of a rotational breeding system, the
      pregnancy rate of 69 Zebu cows was assessed, 32 late postpartum (211 +/- 93 days
      postpartum, LP) and 37 early postpartum (averaging 63 +/- 8 days after calving,
      EP). In the LP group, 60% (19/32) were cycling before exposure to the bulls but
      only 38% (14/37) in the EP group. The two groups were dissimilar from the start
      (p < 0.05). The cows were exposed in a rotational breeding system, with six
      Brahman bulls with previous sexual experience paired off in three groups (A-B, C
      D and E-F). The cows were exposed to each pair of bulls for a period of 3 weeks,
      with one week in between each period, when the females were without the presence
      of a male. In the LP group, the pair of bulls A B obtained a pregnancy rate of
      72% (23/32), whereas for bulls C-D the pregnancy rate was 33% (3/9) and for bulls
      E-F the pregnancy rate was 67% (4/6). In contrast, for the EP cows, bulls A-B
      obtained a pregnancy rate of 32% (12/37), bulls C-D a pregnancy rate of 67%
      (12/18) and for bulls E-F a pregnancy rate of 55% (6/11). The percentage
      pregnancy obtained using the pair of bulls A-B differed (p < 0.05) between LP and
      EP, whereas for bulls C-D and E-F it was similar. The pregnancy rate was
      different (p < 0.05) in the first 3 weeks of mating for the LP group, the highest
      number of cows becoming pregnant during the first 3 weeks of the study. In
      contrast, the highest number of pregnancies in EP occurred evenly during the last
      6 weeks. This study suggests that the reproductive performance of pairs of bulls
      in a 9-week rotational programme with the overall pregnancy rate is similar (94%
      in the LP and 81% in the EP). However, the time taken for the females to become
      pregnant, and hence the performance of the bulls, is related to the average
      number of days postpartum for the cows.

PMID- 14672457
TI  - Smoking: the cloudy, smelly plague.

PMID- 14672458
TI  - Don't run out of stamps.

PMID- 14672459
TI  - Comment on: "The minimum effective dose of estrogen for prevention of
      postmenopausal bone loss".

PMID- 14672460
TI  - Obstetric admissions to the intensive care unit: outcomes and severity of
      illness.
AB  - OBJECTIVE: To determine whether mortality prediction based on a current model of
      outcome prediction is accurate in obstetric patients. METHODS: Consecutive
      obstetric admissions to a medical intensive care unit from 1991 to 1998 were
      reviewed to determine whether mortality prediction is feasible in obstetric
      patients based on a widely used model. The Simplified Acute Physiologic Score
      (SAPS II) was used to predict the probability of hospital mortality. RESULTS: The
      Simplified Acute Physiologic Score overestimated mortality in all patients (19
      predicted deaths, eight observed) but accurately predicted mortality in patients
      admitted to the intensive care unit for medical reasons (seven predicted, five
      observed). The Simplified Acute Physiologic Score did not predict mortality in
      patients admitted for obstetric indications or postpartum hemorrhage. Median SAPS
      II scores were significantly higher in those patients who died, compared with
      survivors. For all groups, SAPS II scores were correlated with intensive care
      unit length of stay but not hospital length of stay. CONCLUSION: The Simplified
      Acute Physiologic Score accurately predicts hospital mortality in obstetric
      patients admitted to the intensive care unit for medical reasons but not for
      indications related to pregnancy and delivery. An alternate model that predicts
      outcomes in obstetric patients admitted for obstetric indications should be
      developed.

PMID- 14672461
TI  - Pelvic embolization for intractable postpartum hemorrhage: long-term follow-up
      and implications for fertility.
AB  - OBJECTIVE: To determine the long-term sequelae of pelvic embolization for
      postpartum hemorrhage and to study the effect on fertility and menses. METHODS:
      Twenty-eight consecutive patients who underwent pelvic embolization for
      postpartum hemorrhage between the years 1977 and 2002 were included in the study.
      Chart review and telephone interviews were conducted to gather data regarding the
      type of delivery, causative factors of the bleeding, preembolization treatments,
      total blood loss, length of time between delivery and embolization,
      complications, long-term side effects, and subsequent pregnancies. RESULTS: The
      average (+/- standard deviation) time to follow-up was 11.7 +/- 6.9 years. The
      most common causes of hemorrhage were vaginal/cervical laceration, placenta
      accreta, and placenta previa. In only one case was the embolization unsuccessful,
      during which there was an accidental perforation of an internal iliac artery
      resulting in a retroperitoneal hematoma and subsequent total abdominal
      hysterectomy. All of the interviewed patients that desired to get pregnant after
      embolization were able to do so. Six patients reported a total of six
      uncomplicated pregnancies and deliveries in the years after their embolization.
      Of the remaining patients interviewed, none made subsequent attempts to get
      pregnant. The most commonly reported long-term side effects were transient
      buttock numbness (n = 2) and urinary frequency (n = 2). In no patients were the
      side effects severe enough to seek further medical attention. CONCLUSION: Pelvic
      arterial embolization is a safe and effective procedure and offers patients a
      fertility-preserving alternative to hysterectomy for treatment of intractable
      postpartum hemorrhage.

PMID- 14672462
TI  - Vaginal versus cesarean delivery for breech presentation in California: a
      population-based study.
AB  - OBJECTIVE: To examine the population-based pregnancy outcomes associated with
      vaginal breech delivery. METHODS: A retrospective, population-based cohort study
      of all term (greater than 37 weeks' gestation), normal birth weight (2.5-3.8 kg),
      nonanomalous newborns in California, from January 1, 1991 to December 31, 1999
      was performed. Neonatal mortality and major neonatal morbidity were compared by
      route of delivery for cephalic (3,271,092) and breech (100,730) presentations.
      RESULTS: More than 3.2 million singleton term newborns were identified during the
      study period, with 100,667 (3%) in breech presentation at the time of delivery.
      Of these, 4952 women (4.9%) had vaginal breech delivery, whereas 60,418 women
      delivered by cesarean without labor, and 35,297 women underwent cesarean in
      labor. Breech vaginal delivery in nulliparous women was associated with increased
      neonatal mortality (odds ratio [OR] 9.2, 95% confidence interval [CI] 3.3, 25.6)
      and morbidity (asphyxia: OR 5.7, 95% CI 4.5, 7.3; brachial plexus injury: OR
      33.9, 95% CI 15.2, 76.1; and birth trauma: OR 5.8, 95% CI 4.7, 7.1) compared with
      breech delivery by prelabor cesarean in nulliparous women. In breech-presenting
      women with one prior vaginal delivery, neonatal mortality was not different
      between groups, but morbidities (asphyxia: OR 3.9, 95% CI 3.0, 5.1; brachial
      plexus injury: OR 22.4, 95% CI 9.9, 50.5; and birth trauma: OR 4.2, 95% CI 3.4,
      5.3) remained increased for vaginal compared with cesarean delivery. CONCLUSION:
      The "normal" term breech fetus, when delivered vaginally, had significantly
      increased neonatal mortality (in nulliparous women) and morbidity (all breech
      deliveries), when compared with the breech fetus delivered by cesarean, which
      suggests that these patients might best be delivered by cesarean to avoid these
      adverse outcomes.

PMID- 14672463
TI  - Emergency contraception: pharmacy access in Albuquerque, New Mexico.
AB  - OBJECTIVE: Emergency contraception could reduce the approximately 3 million
      unintended pregnancies that occur annually in the United States. Dedicated
      emergency contraception products may be particularly useful because instructions
      are easy to understand and simple to follow. However, they must be available
      within a few days to women who have had unprotected intercourse. The goal of this
      study was to investigate whether women presenting to pharmacies in a moderately
      sized metropolitan area with a prescription for Plan B or Preven could get it
      filled. METHODS: Two research assistants posed as women needing emergency
      contraception. They visited 89 pharmacies in Albuquerque, New Mexico, presenting
      a prescription for either Plan B or Preven. The assistants recorded the
      availability of the products in the pharmacies. When the product was not in
      stock, the research assistants asked pharmacy providers why the products were not
      carried. Fisher exact test was performed to compare categoric data. RESULTS: Plan
      B and Preven were in stock at only 19 visits (11%). Of the pharmacies that did
      not stock the products, 53% reported they could obtain Plan B or Preven within 24
      hours. The most common reason cited by pharmacy providers for not stocking Plan B
      or Preven was the lack of prescriptions received for them (65%). CONCLUSION: Plan
      B and Preven were not in stock at the majority of pharmacies in a moderately
      sized metropolitan area. Lack of availability at the pharmacy constitutes a major
      barrier to emergency contraception access.

PMID- 14672464
TI  - Plasma low-density lipoprotein cholesterol and bone mass densitometry in
      postmenopausal women.
AB  - OBJECTIVE: The prevalence and the clinical and social importance of osteopenia
      and osteoporosis are increasing in western societies. To improve knowledge of the
      risk factors associated with these conditions, we assessed the relationship
      between bone mass density and plasma lipid profile in a cohort of postmenopausal
      women. METHODS: We studied 1303 postmenopausal women who attended a menopause
      outpatient clinic. All women underwent bone mineral density determination at the
      level of the lumbar spine. Plasma lipids and lipoproteins and bone metabolic
      markers were assessed on a blood sample obtained after a 12-hour fast. RESULTS:
      Statistically significant associations were found by univariate analysis between
      prevalence of osteopenia and age, time since menopause, body mass index, and low
      density lipoprotein (LDL) cholesterol. Specifically, women with plasma LDL
      cholesterol levels of at least 160 mg/dL had a more than doubled probability of
      being osteopenic compared with women with lower LDL cholesterol (47.9% versus
      21.2%, respectively). Time since menopause, body mass index, and LDL cholesterol
      were the only variables significantly associated with the prevalence of
      osteopenia, by multivariable analysis. CONCLUSION: Postmenopausal women with
      increased plasma LDL cholesterol levels had a greater probability of being
      classified as osteopenic than women with normal plasma LDL cholesterol levels.
      Our data, if confirmed, suggest that elevated levels of plasma LDL cholesterol
      should be regarded as an additional risk factor for reduced bone mineral density.

PMID- 14672465
TI  - Bacterial vaginosis in sexually experienced and non-sexually experienced young
      women entering the military.
AB  - OBJECTIVE: To estimate the prevalence of bacterial vaginosis by Nugent Gram stain
      criteria in a nonclinic national sample of young women entering recruit training;
      to examine clinical associations with bacterial vaginosis; and to evaluate the
      performance of a pH test card and Papanicolaou smear against Gram stain as
      screening tools for bacterial vaginosis. METHODS: A cross-sectional study of 1938
      women was conducted. Self-collected vaginal swabs were applied to a colorimetric
      pH test card and a glass slide for Gram stain evaluation according to the Nugent
      criteria. Papanicolaou smears and samples for sexually transmitted diseases
      screening were collected during routine entry pelvic examinations. RESULTS:
      Bacterial vaginosis prevalence was 27%, with 28% in sexually experienced and 18%
      in non-sexually experienced women (P = .001). Bacterial vaginosis prevalence was
      11% in Asian/Pacific Islanders, which was lower than in other nonwhite ethnic
      groups (P = .004). Clinically, bacterial vaginosis was directly related to
      multiple sexual partners (P = .026), self-report of vaginal discharge (P = .001),
      self-report of vaginal odor (P < .001), and concurrent Chlamydia trachomatis
      infection (P = .002), and inversely related to hormonal contraceptive use (P =
      .013). Vaginal discharge did not achieve statistical significance in multivariate
      analysis. Compared with the Nugent criteria, the sensitivities and specificities
      for bacterial vaginosis diagnosis were as follows: colorimetric pH test: 72% and
      67%; Papanicolaou smear: 72% and 79%, respectively. CONCLUSION: Among these
      diverse young women, bacterial vaginosis occurs commonly in both sexually
      experienced and inexperienced young women and differs by race and ethnicity. The
      pH colorimetric test and Papanicolaou smear performed moderately well as
      screening tools for bacterial vaginosis. The inverse relationship of bacterial
      vaginosis with hormonal contraceptive use and its direct relationship with C.
      trachomatis need further study.

PMID- 14672466
TI  - Lower quality of life among women with chronic pelvic pain after pelvic
      inflammatory disease.
AB  - OBJECTIVE: To evaluate the morbidity from chronic pelvic pain after pelvic
      inflammatory disease (PID). METHODS: A total of 547 women were studied as part of
      the PID Evaluation and Clinical Health (PEACH) Study. Chronic pelvic pain was
      defined as pelvic pain reported at two or more consecutive interviews conducted
      every 3 to 4 months through 32 months and was graded as mild to moderate (low
      pain intensity) or moderate to severe (high pain intensity). Mean Medical
      Outcomes Study Short Form (SF-36) scores at 32 months were compared by chronic
      pelvic pain categories. RESULTS: The mean (+/- standard deviation) physical
      health composite scores and mental health composite scores from the SF-36 were
      progressively lower among women with increasing grade of chronic pelvic pain
      (physical health composite scores: no chronic pelvic pain = 87.3 +/- 10.7, mild
      to moderate chronic pelvic pain = 79.1 +/- 14.6, moderate to severe chronic
      pelvic pain = 73.6 +/- 16.0, P < .01; mental health composite scores: no chronic
      pelvic pain = 78.7 +/- 13.6, mild to moderate chronic pelvic pain = 69.1 +/-
      15.8, moderate to severe chronic pelvic pain = 67.5 +/- 17.1, P < or = .01).
      Individual physical function, bodily pain, general health, vitality, social
      function, and mental health scores were also significantly lower among women with
      chronic pelvic pain and by increasing grade of pain intensity. CONCLUSION:
      Chronic pelvic pain after PID is associated with reduced physical and mental
      health.

PMID- 14672467
TI  - Predictors of outcome in the behavioral treatment of urinary incontinence in
      women.
AB  - OBJECTIVE: To identify predictors of outcome of a multicomponent behavioral
      training program for urge and stress incontinence in women. METHODS: This report
      is a secondary analysis of data from three prospective, randomized, clinical
      trials testing behavioral interventions for urinary incontinence. Participants
      were a volunteer sample of 258 ambulatory, nondemented, community-dwelling women,
      aged 40-92 years, with stress, urge, or mixed urinary incontinence. Participants
      received 8 weeks (four visits) of multicomponent behavioral training in each
      study. The relationship between a number of variables and treatment success were
      explored by univariate and multivariable logistic regression analyses. RESULTS:
      Successful treatment of predominantly urge incontinence (75% reduction of
      incontinent episodes as recorded on bladder diary) was associated with not
      wearing any form of protection for incontinence (P = .045; 95% confidence
      interval [CI] .282, .987). Achieving total continence (100% reduction) was
      associated with fewer incontinent episodes at baseline (P < .001; 95% CI .138,
      .557), previous surgery for incontinence (P = .021; 95% CI 1.169, 6.543), and
      lower education level (P = .022; 95% CI .175, .871). Successful treatment of
      predominantly stress incontinence (75% reduction) was related to not having
      previous evaluation or treatment for incontinence (P = .001; 95% CI .026, .415),
      and fewer incontinent episodes on baseline bladder diary (P = .026; 95% CI .210,
      .907). Outcomes were not associated with age, race, type of incontinence, or a
      number of other variables reflecting medical history, obstetric history,
      medications, pelvic examination, body mass index, urodynamic parameters, or
      psychological distress. CONCLUSION: Aside from indicators of severity and
      previous treatment, there were few associations between baseline clinical
      variables and outcome of behavioral treatment.

PMID- 14672468
TI  - Duty hours and pregnancy outcome among residents in obstetrics and gynecology.
AB  - OBJECTIVE: To assess the present status of resident duty hours in obstetrics and
      gynecology, identify existing policies concerning work schedules during
      pregnancy, and evaluate pregnancy outcome in female house officers. METHODS: A
      questionnaire-based study was administered to residents taking the 2001 Council
      on Residency Education in Obstetrics and Gynecology examination. RESULTS: More
      than 90% of the residents reported that their institution had a maternity leave
      policy. The leave was usually 4-8 weeks long and was paid. Nearly 95% of
      residents reported that they had to take over the work of residents on maternity
      leave. Most women residents worked more than 80 hours weekly throughout
      pregnancy, and few took time off before delivery. Most pregnancies occurred
      during the fourth year of training and did not seem to be adversely affected by
      the long work hours. CONCLUSION: This study, performed before the institution of
      the new Accreditation Council for Graduate Medical Education resident duty hour
      policies, demonstrated that, although women house officers continued to work more
      than 80 hours per week during pregnancy, most had a good pregnancy outcome.
      Nevertheless, there was a higher frequency of preterm labor, preeclampsia, and
      fetal growth restriction in female residents than in spouses or partners of male
      residents.

PMID- 14672469
TI  - Vertical skin incisions and wound complications in the obese parturient.
AB  - OBJECTIVE: To examine the relationship between the type of skin incision and
      postoperative wound complications in an obese population. METHODS: A hospital
      based perinatal database was used to identify women with a body mass index (BMI)
      of greater than 35 undergoing their first cesarean delivery. Hospital and
      outpatient medical records were reviewed for the following variables: age,
      insurance status, BMI, gestational age at delivery, birth weight, smoking
      history, prior abdominal surgery, existing comorbidities, preoperative
      hematocrit, chorioamnionitis, duration of labor and membrane rupture, dilation at
      time of cesarean delivery, type of skin and uterine incision, estimated blood
      loss, operative time, antibiotic prophylaxis, use of subcutaneous drains or
      sutures, endometritis, and length of stay. The primary outcome variable was any
      wound complication requiring opening the incision. Multiple logistic regression
      analysis was completed to determine which of these factors contributed to the
      incidence of wound complications. RESULTS: From 1994 to 2000, 239 women with a
      BMI greater than 35 undergoing a primary cesarean delivery were identified. The
      overall incidence of wound complications in this group of severely obese patients
      was 12.1%. Factors associated with wound complications included vertical skin
      incisions (odds ratio [OR] 12.4, P < .001) and endometritis (OR 3.4, P = .03). A
      high preoperative hematocrit was protective (OR .87, P = .03). No other factors
      were found to impact wound complications. CONCLUSION: Primary cesarean delivery
      in the severely obese parturient has a high incidence of wound complications. Our
      data indicate that a vertical skin incision is associated with a higher rate of
      wound complications than a transverse incision.

PMID- 14672470
TI  - Single additional dose postpartum therapy for women with chorioamnionitis.
AB  - OBJECTIVE: To determine whether a short course of antibiotics provides adequate
      treatment for chorioamnionitis. METHODS: Women received intravenous ampicillin, 2
      g every 6 hours, and gentamicin, 1.5 mg/kg every 8 hours, when clinical
      chorioamnionitis was diagnosed. After delivery, subjects were randomized to
      continue this regimen until afebrile and asymptomatic for 24 hours (control
      group) or to receive only the next scheduled dose of each drug (study group). If
      delivered via cesarean, patients received clindamycin, 900 mg intravenously, at
      umbilical cord clamping. The control group continued receiving clindamycin every
      8 hours until antibiotics were discontinued. The primary outcome was treatment
      failure, defined as a single temperature after the first postpartum dose of
      antibiotics of 39.0C or more, or two temperatures 38.4C or more at least 4 hours
      apart. To detect a 150% increase in rate of treatment failures from 8% in the
      control group to 20% in the study group, 292 subjects were needed (alpha = .05; 1
      - beta = .80). RESULTS: From December 26, 1999, to March 18, 2003, a total of 292
      women were enrolled in the study. In the intent-to-treat analysis, treatment
      failure rate did not differ between the control (n = 141) and study (n = 151)
      groups (3.5% versus 4.6%; P = .639). CONCLUSION: If treated promptly intrapartum,
      one additional dose of a broad-spectrum combination of antibiotics is sufficient
      postpartum therapy for immune-competent women with chorioamnionitis.

PMID- 14672471
TI  - Histologic endometritis in asymptomatic human immunodeficiency virus-infected
      women: characterization and effect of antimicrobial therapy.
AB  - OBJECTIVE: To estimate the prevalence, risk factors, clinical symptoms and signs,
      and response to antimicrobial therapy of histologic endometritis in human
      immunodeficiency virus (HIV)-infected women without clinical salpingitis.
      METHODS: This was a cross-sectional study of 42 HIV-infected women enrolled from
      a single clinic. Subjects underwent standardized history, examination, and
      laboratory determinations, including endometrial biopsy. Women with suspected
      pelvic inflammatory disease were excluded. All women were given antibiotics and
      repeat evaluation in 5-7 weeks. Histologic endometritis was defined by at least
      one stromal plasma cell per 120x field and five or more surface polymorphonuclear
      leukocytes per 400x field. Chi-square and Fisher exact tests were used as
      appropriate. RESULTS: Histologic endometritis was present among 16 (38%) of 42
      evaluable HIV-infected women, none of whom had Chlamydia trachomatis or Neisseria
      gonorrhoeae. Douching three or more times per month, history of ectopic
      pregnancy, and two or more prior urinary tract infections were associated with
      endometritis, as was elevated erythrocyte sedimentation rate (P < or = .05).
      Physical examination findings and mean CD4+ lymphocyte count were similar among
      those with and without endometritis. In the nine HIV-infected women with a repeat
      biopsy, endometritis decreased from four (44%) to two (22%) after treatment (P =
      .30). CONCLUSION: The prevalence of histologic endometritis in HIV-infected women
      was high despite few examination findings and no demonstrated pathogens.
      Endometritis in HIV-infected women might be related to pathogens not evaluated,
      to prior infection, or to reduced immunity from HIV.

PMID- 14672472
TI  - Postpartum varicella vaccination: is the vaccine virus excreted in breast milk?
AB  - OBJECTIVE: To evaluate whether the varicella vaccine virus is detected in breast
      milk after vaccination of breast-feeding women and whether there is serologic
      evidence of exposure of the infant to varicella virus after maternal vaccination.
      METHODS: We enrolled women identified as varicella seronegative during routine
      prenatal screening at Group Health Cooperative. Participants received the first
      dose of varicella vaccine at least 6 weeks postpartum and the second dose at
      least 4 weeks later. They collected ten breast milk samples after each vaccine
      dose. Breast milk samples were tested for varicella zoster virus by polymerase
      chain reaction (PCR). Serum specimens were collected from the mothers 1 month
      after each vaccine dose, and peripheral blood from their infants was collected
      onto filter spots 1 month after the mother's second dose. These samples were
      tested for varicella immunoglobulin (Ig) G by whole-virus enzyme-linked
      immunosorbent assay (ELISA), or by the more sensitive glycoprotein ELISA. When
      possible, filter spots from the infants were also tested by PCR for the presence
      of varicella zoster virus deoxyribonucleic acid (DNA). RESULTS: Twelve women were
      enrolled; all seroconverted after the first vaccine dose. Varicella DNA was not
      detected by PCR in any of the 217 postvaccination breast milk specimens. None of
      the infants was seropositive. Samples from six infants were tested for varicella
      zoster virus DNA by PCR, and all were negative. CONCLUSION: We found no evidence
      of varicella vaccine virus excretion in breast milk. These findings suggest that
      postpartum vaccination of varicella-susceptible women need not be delayed because
      of breast-feeding.

PMID- 14672473
TI  - Trends in gestational choriocarcinoma: a 27-year perspective.
AB  - OBJECTIVE: To evaluate trends in incidence and survival rates for gestational
      choriocarcinoma with the use of population-based data. METHODS: Overall and 5
      year average age-adjusted incidence rates were computed with the Surveillance,
      Epidemiology, and End Results program public-use database. Differences by age at
      diagnosis, race, stage, registry, and over calendar time were compared by Poisson
      regression, and survival censored for deaths other than choriocarcinoma by log
      rank tests and Cox's proportional hazard ratios. RESULTS: Between 1973 and 1999,
      450 cases were recorded. The annualized age-adjusted incidence rate for
      choriocarcinoma was 0.133 per 100,000 woman-years and decreased by 49.7% (2.8%
      per year). By race (whites, blacks, and others), incidence rates declined by
      62.3%, 27.2%, and 54.3%, respectively. In the Poisson model evaluating incidence
      rates, age, race, registry, and stage were significant main effects. Compared
      with whites, the relative risk was higher for blacks (2.14, 95% confidence
      interval [CI] 1.60, 2.86) and others (2.30, 95% CI 1.67, 3.18). Rates were
      highest in Utah and lowest in Iowa. By age at diagnosis, rates were higher in 20
      39-year-olds. The 5-year relative survival rate was 89.5%. Censored survival was
      significantly lower among blacks (whites 92.4%, blacks 84.9%, others 87.1%, P =
      .045), for advanced disease (localized 94.5%, regional 92.9%, distant 87.1%, P =
      .02), and with increasing age at diagnosis (P = .017). Age and calendar time
      significantly influenced censored survival independent of stage and registry.
      CONCLUSION: Gestational choriocarcinoma incidence rates have declined and
      survivals have improved, but blacks continue to have higher incidence and lower
      survival rates.

PMID- 14672474
TI  - Primary abdominal gestational choriocarcinoma.
AB  - BACKGROUND: Gestational choriocarcinoma associated with ectopic pregnancy is an
      extremely infrequent event. Primary abdominal gestational choriocarcinoma has not
      been previously described. CASE: A pregnant woman presented to the emergency room
      with 6 days of vaginal spotting. Her last menstrual period suggested a gestation
      at 6 4/7 weeks. Transvaginal sonogram showed a hemoperitoneum with no
      intrauterine pregnancy. The serum human chorionic gonadotropin level was noted to
      be 317,735 mIU/mL. A 20 x 20-mm friable, bleeding mass on the left anterior
      abdominal wall was laparoscopically resected. Gestational choriocarcinoma was
      identified on histopathologic review. International Federation of Gynecology and
      Obstetrics stage IV:4 was assigned, and the patient achieved clinical remission
      with combination chemotherapy. CONCLUSION: Primary abdominal gestational
      choriocarcinoma can present with findings similar to a ruptured ectopic
      pregnancy; it should be treated by surgical excision and chemotherapy.

PMID- 14672475
TI  - Ovarian choriocarcinoma arising from partial mole as evidenced by
      deoxyribonucleic acid microsatellite analysis.
AB  - BACKGROUND: Recent developments in genetic analysis allow determination of the
      origin of choriocarcinoma (ie, gestational or nongestational), which helps
      determine the strategy for clinical treatment of the disease. CASE: We present a
      case of ovarian choriocarcinoma forming a huge ovarian mass 40 days after the
      patient's last menstrual period. Deoxyribonucleic acid microsatellite analysis of
      the tumor revealed that it contained a single maternal and two paternal alleles
      at several independent loci, consistent with the tumor resulting from ovarian
      pregnancy of a partial hydatidiform mole. CONCLUSION: This is the first
      description of an ovarian pregnancy of a partial hydatidiform mole-derived
      ovarian choriocarcinoma.

PMID- 14672476
TI  - Human chorionic gonadotropin and vascular endothelial growth factor in normal and
      complicated pregnancies.
AB  - OBJECTIVE: To study the relationships between maternal serum concentrations of
      beta-human chorionic gonadotropin (hCG) and vascular endothelial growth factor
      (VEGF) in both normal pregnant women during late pregnancy and women with
      pregnancy complications. METHODS: Sixty-six women in three groups were
      prospectively studied: 1) women diagnosed with fetal growth restriction (n = 22),
      2) women with preeclampsia (n = 22), and 3) healthy pregnant women (controls)
      frequency matched for age, parity, and gestational age (n = 22). Primary outcomes
      were maternal serum concentrations of both beta-hCG and VEGF. Placental
      insufficiency was defined by a pulsatility index in umbilical artery greater than
      the 99th percentile for gestation. RESULTS: Maternal serum concentrations of beta
      hCG and VEGF were greater in women with preeclampsia than in controls (P = .001
      and P = .002, respectively) and women with fetal growth restriction (P = .002 and
      P = .002, respectively). Concentrations did not differ between women with fetal
      growth restricted fetuses and controls. Correlation between beta-hCG and VEGF was
      not significant in any of the studied groups. Serum VEGF concentrations were
      significantly increased in a subgroup of 12 women with placental insufficiency (P
      = .04) and correlated with beta-hCG concentrations (r = .63, P = .02).
      CONCLUSION: Both VEGF and beta-hCG maternal serum concentrations were increased
      in women with preeclampsia but normal in women with fetal growth restriction,
      although VEGF concentrations were increased in those cases with placental
      insufficiency. Maternal serum beta-hCG and VEGF concentrations did not correlate
      except in women with placental insufficiency.

PMID- 14672477
TI  - Validation of a Spanish version of the Pelvic Organ Prolapse Incontinence Sexual
      Questionnaire.
AB  - OBJECTIVE: To develop a validated Spanish version of the Pelvic Organ Prolapse
      Incontinence Sexual Questionnaire (PISQ). METHODS: The PISQ is a previously
      described validated and reliable questionnaire. We used a back-translation method
      to develop a Spanish-language version. Twenty-six bilingual patients with pelvic
      organ prolapse and/or urinary incontinence were randomized to complete either the
      original English version or the final Spanish version of the PISQ first, followed
      by the other questionnaire. Scores of the two versions were compared. Paired t
      test for total PISQ and its three domain scores and Wilcoxon signed rank test for
      each item assessed the bias between the two equivalent versions. Agreement
      between the two versions was assessed by weighted kappa statistics, with 95%
      confidence intervals for each item. P values of .05 or less were considered
      significant, and kappa values of .75 or greater were considered to indicate good
      agreement. RESULTS: English and Spanish versions demonstrated no differences for
      each of the factors and total scores (P = .15, .83, .28, and .56, respectively).
      Wilcoxon signed rank test demonstrated that one item was answered differently in
      the English and Spanish versions. Good agreement between Spanish and English
      versions in 30 of the 31 items was demonstrated by weighted kappa statistics.
      Overall, 72% of women scored both versions of the questionnaire equivalently.
      CONCLUSIONS: We have developed a validated and reliable Spanish questionnaire to
      evaluate sexual functioning in Spanish-speaking patients with pelvic organ
      prolapse and/or urinary incontinence.

PMID- 14672478
TI  - Childbearing beyond maternal age 50 and fetal outcomes in the United States.
AB  - OBJECTIVE: To estimate whether achieving pregnancy beyond maternal age of 50
      years compromises fetal well-being and survival. METHODS: This was a
      retrospective study on all deliveries in the United States from 1997 to 1999.
      Four maternal age groups of 20-29 (young), 30-39 (mature), 40-49 (very mature),
      and 50 or more years (older) were constructed to assess risk gradients for fetal
      morbidity and mortality. RESULTS: A total of 539 deliveries among older mothers
      (aged 50 and above) were documented (four per 100,000). Among singleton
      gestations, the risks for low birth weight, preterm, and very preterm were
      tripled among older mothers, whereas the occurrence of very low birth weight,
      small size for gestational age, and fetal mortality were approximately doubled
      compared with those for young mothers. Older mothers also had greater risks for
      fetal morbidity and mortality than their immediate younger counterparts (40-49
      year olds) except for very low birth weight. Among multiple gestations, the
      differences in risk between older and young mothers were lower than those noted
      among singletons. Still, compared with young mothers, older mothers had
      significantly higher risks of low birth weight, very low birth weight, very
      preterm, and small size for gestational age. Older mothers also had higher risk
      estimates for multiples than 40-49-year-old gravidas in terms of all fetal
      morbidity and mortality indices. CONCLUSION: Pregnancy beyond age 50 was
      associated with increased risks for the fetus. Our findings suggest that this age
      group is a distinct obstetric high-risk entity that requires special counseling
      before and after conception.

PMID- 14672479
TI  - Pregnancy-related mortality among women aged 35 years and older, United States,
      1991-1997.
AB  - OBJECTIVE: To describe pregnancy-related deaths among women 35 years and older
      and to compare their risk of death to that for 25-29-year-old women. METHODS:
      Pregnancy-related deaths in the United States among women 35 years and older from
      1991 through 1997 were identified through the Center for Disease Control and
      Prevention's Pregnancy Mortality Surveillance System. Pregnancy-related mortality
      ratios (deaths per 100,000 live births) and risk ratios (compared with 25-29-year
      old women) for women 35-39 years old or 40 years and older were calculated and
      stratified by race, obstetric and demographic variables, and cause of death.
      RESULTS: There was an excess risk of death for women 35 years and older
      regardless of parity, time of entry into prenatal care, and level of education.
      Among white women, the risk ratios for death from hemorrhage, infection,
      embolisms, hypertensive disorders of pregnancy, cardiomyopathy, cerebrovascular
      accidents, or other medical conditions ranged from 1.8 to 2.7 for those aged 35
      39 years and from 2.5 to 7.9 for those 40 years and older. Among black women the
      risk ratios for death from these conditions ranged from 2.0 to 4.1 for those aged
      35-39 years and from 4.3 to 7.6 for those 40 years and older. CONCLUSION:
      Recognition of the risk of death borne by older pregnant women is needed to
      inform their care before, during, and after pregnancy. Thorough review of all
      maternal deaths as a core public health function may shed light on the reasons
      for excess pregnancy-related mortality among older women.

PMID- 14672480
TI  - Prepregnancy weight and adverse perinatal outcomes in an ethnically diverse
      population.
AB  - OBJECTIVE: To examine the association between excessive prepregnancy weight and
      adverse outcomes, with a focus on women weighing over 200 lbs (91 kg) before
      pregnancy. METHODS: Data were from the 1998-1999 New York City births file for
      213,208 singletons with information on prepregnancy weight. Five categories of
      prepregnancy weight were constructed and used to predict gestational diabetes,
      preeclampsia, cesarean delivery, very low birthweight, macrosomia, and treatment
      in the neonatal intensive care unit (NICU). Statistical adjustments were made for
      mother's age, race or ethnicity, marital status, education, parity, social risk
      (eg, smoking), initiation of prenatal care, health insurance, and infant's sex.
      RESULTS: Maternal prepregnancy weight was associated with several adverse
      outcomes. Women in the heaviest group (> 300 lbs or > 136 kg) had the highest
      adjusted odds ratios (OR) for gestational diabetes (OR 5.2), preeclampsia (OR
      5.0), and cesarean delivery (OR 2.7) compared with women weighing 100-149 lbs (45
      67 kg). Compared with the reference group, the heaviest women were more likely to
      have a macrosomic infant and an infant treated in the NICU (OR 4.2 and 1.9,
      respectively). Even among a subsample of women who did not have any diabetic or
      hypertensive diseases, excess weight significantly increased the likelihood of
      macrosomia and NICU treatment. Blacks were disproportionately represented in the
      two heaviest groups (49.8% of those weighing 200-299 lbs and 63.9% of those
      weighing over 300 lbs). CONCLUSION: In this population-based study of pregnant
      women, the adverse outcomes associated with excessive weight underline the
      urgency of weight loss interventions before pregnancy. The analysis also suggests
      that research is needed on rapidly growing racial or ethnic subgroups most at
      risk for obesity.

PMID- 14672481
TI  - Perinatal outcome after prenatal diagnosis of placental chorioangioma.
AB  - OBJECTIVE: To review the prenatal complications, management, and perinatal
      outcome in pregnancies complicated by placental chorioangioma. METHODS: Cases of
      placental chorioangioma diagnosed prenatally as part of a prospective,
      multicentric program for fetal diagnosis and therapy were identified. All cases
      were evaluated with color flow imaging. In the latter part of the study, three
      dimensional power Doppler angiography was also used to study the vascular pattern
      of the tumor. Information on maternal demographics, prenatal sonographic
      findings, pregnancy complications, antenatal intervention, and perinatal outcome
      was obtained by reviewing the medical records or contacting the referring
      obstetricians. RESULTS: In the 5-year period from January 1997 to December 2001,
      11 cases of placental chorioangioma were diagnosed prenatally. Nine cases were
      diagnosed in singleton and two in twin pregnancies. Among the nine cases
      occurring in singletons, five (56%) were associated with pregnancy complications,
      including polyhydramnios (n = 3), oligohydramnios (n = 2), fetal growth
      restriction (n = 2), and nonimmune hydrops (n = 1). Amniodrainage was required in
      one of these cases, allowing prolongation of pregnancy until term. Four (44%)
      singletons delivered before 35 weeks. Overall, two fetuses died, including one
      twin due to complications of twin-twin transfusion syndrome and another with
      hydrops after alcohol injection into the chorioangioma. In four pregnancies, no
      prenatal complications were detected in spite of continuous growth and
      vascularity of the placental mass in three of them. CONCLUSION: Placental
      chorioangioma is associated with an increased risk of pregnancy complications,
      the most common being polyhydramnios and preterm delivery. In selected cases,
      amniodrainage allows continuation of the pregnancy with improving perinatal
      outcome. Fetuses who develop hydrops are at the highest risk for perinatal death,
      with limited therapeutic options being available. Close follow-up is advised,
      even in those cases with no associated findings at the time of the diagnosis.

PMID- 14672482
TI  - Transurethral resection of tension-free vaginal tape penetrating the urethra.
AB  - BACKGROUND: The penetration of a tension-free vaginal tape into the urethra is a
      rarely described complication. It might occur much more often, given the common
      clinical practice of tension-free vaginal tape implantation. We describe a less
      invasive approach to resection than the transvaginal urethral resection method
      previously reported in the literature. CASE: A 68-year-old woman with stress
      urinary incontinence underwent a tension-free vaginal tape procedure. After
      surgery, the woman complained about pain and voiding disorders. A urodynamic
      investigation performed 14 months later revealed an infravesical obstruction
      caused by parts of the tension-free vaginal tape penetrating the urethra. After
      transurethral resection of the mesh, voiding returned to normal, and the patient
      remained subjectively and objectively continent. CONCLUSION: The transurethral
      approach described is a minimally invasive and successful technique that should
      be tried before embarking on major destructive and reconstructive surgery on the
      urethra.

PMID- 14672483
TI  - Foley balloon to tamponade bleeding in the retropubic space.
AB  - BACKGROUND: Hemorrhage from the retropubic space is a well-described complication
      of the tension-free vaginal tape procedure that can be difficult to control with
      conservative measures. CASE: A 40-year-old female patient underwent tension-free
      vaginal tape procedure to treat stress incontinence. The procedure was
      complicated by persistent intraoperative bleeding from the retropubic space. The
      hemorrhage was refractory to digital tamponade but was successfully controlled by
      tamponade with a Foley catheter. The catheter was inserted with use of the
      urology guide wire from the vagina along the path of the tunneler into the
      retropubic space and inflated, successfully controlling the hemorrhage.
      CONCLUSION: Persistent bleeding during tension-free vaginal tape procedure from
      the retropubic space can be controlled with a Foley catheter placed from the
      vagina into the space of Retzius.

PMID- 14672484
TI  - The axial location of structural regions in the urethra: a magnetic resonance
      study in nulliparous women.
AB  - OBJECTIVE: To define and quantify the appearance and location of distinct regions
      of the bladder neck and urethra by using axial magnetic resonance images from
      healthy, continent, nulliparous women. METHODS: Seventy-eight asymptomatic,
      healthy, nulliparous women (mean age 29.2 +/- 5.4 years) volunteered for this
      study. All women were proven continent on urodynamic examination. Axial proton
      density magnetic resonance images of the pelvic floor were analyzed at 5-mm
      intervals. A geometric origin was established at the internal urethral meatus.
      The presence or absence of each of six structural regions--the bladder base,
      bladder neck, striated urethral sphincter, compressor urethrae and urethrovaginal
      sphincter, perineal membrane, and distal urethra--was then noted in each more
      distal image. The proportion of women in whom a structural region was seen at
      each 5-mm interval was recorded. RESULTS: The striated urogenital sphincter was
      observed at 5-25 mm distal to the bladder base. It was observed 10 and 15 mm
      below the bladder base in 91% (95% confidence interval [CI] 85%, 98%) and 99%
      (95% CI 97%, 100%), respectively, of all women. The perineal membrane, marking
      the distal end of the muscular urethra, was located 20-35 mm distal to the
      bladder base. The length of the muscular region of the urethra ranged from 20 to
      35 mm (mean 24 mm, 95% CI 24, 25 mm). CONCLUSION: Magnetic resonance images allow
      the normal appearance and location of urethral and bladder neck structures to be
      quantified in healthy, continent, nulliparous women.

PMID- 14672485
TI  - Folic acid awareness in Michigan, 1996-1999.
AB  - OBJECTIVE: To evaluate the prevalence and trend of folic acid awareness among
      Michigan mothers during 1996-1999 and to identify maternal characteristics
      predictive of folic acid awareness. METHODS: We analyzed data from the Michigan
      Pregnancy Risk Assessment Monitoring System, a population-based survey of women
      with recent live births. A positive response to the question, "Before you became
      pregnant, did you know that folic acid could help prevent some birth defects?"
      was used as an indicator of folic acid awareness. Logistic regression was used to
      evaluate trends in folic acid awareness prevalence and the association between
      folic acid awareness and certain maternal characteristics. RESULTS: Of the women
      invited to participate, 7252 responded (67.3%). Overall, folic acid awareness
      increased from 1996 to 1999 (60.3-71.4%; P < .001). However, folic acid awareness
      decreased for women with no high school education from 1997 to 1999 (59.3-13.8%,
      P = .05). In addition, folic acid awareness was lower among black women (adjusted
      odds ratio [OR] 0.43; 95% confidence interval [CI] 0.4, 0.5, versus other races),
      women with unplanned pregnancies (adjusted OR 0.6; 95% CI 0.5, 0.8, versus those
      with planned pregnancies), and those with no high school education (adjusted OR
      0.08; 95% CI 0.03, 0.2, versus women with college education). CONCLUSION:
      Although folic acid awareness has increased among Michigan mothers overall during
      1996-1999, it has decreased among women with less than a high school education,
      and substantial gaps exist among socioeconomic subgroups. Continued efforts are
      needed to improve folic acid awareness and consumption of folic acid among women
      of reproductive age, with special attention focused on populations experiencing
      gaps or declines in folic acid awareness.

PMID- 14672486
TI  - Group prenatal care and preterm birth weight: results from a matched cohort study
      at public clinics.
AB  - OBJECTIVE: To examine the impact of group versus individual prenatal care on
      birth weight and gestational age. METHODS: This prospective, matched cohort study
      included pregnant women (N = 458) entering prenatal care at 24 or less weeks'
      gestation; one half received group prenatal care with women of the same
      gestational age. Women were matched by clinic, age, race, parity, and infant
      birth date. Women were predominantly black and Hispanic of low socioeconomic
      status, served by one of three public clinics in Atlanta, Georgia or New Haven,
      Connecticut. RESULTS: Birth weight was greater for infants of women in group
      versus individual prenatal care (P < .01). Among those born preterm, infants of
      group patients were significantly larger than infants of individual-care patients
      (mean, 2398 versus 1990 g, P < .05). Although not statistically significant,
      infants of group patients were less likely than those of individual-care patients
      to be low birth weight (less than 2500 g; 16 versus 23 infants); very low birth
      weight (less than 1500 g; three versus six infants); early preterm (less than 33
      weeks; two versus seven infants); or to experience neonatal loss (none versus
      three infants). There were no differences in number of prenatal visits or other
      risk characteristics (patient age, race, prior preterm birth). CONCLUSIONS: Group
      prenatal care results in higher birth weight, especially for infants delivered
      preterm. Group prenatal care provides a structural innovation, permitting more
      time for provider-patient interaction and therefore the opportunity to address
      clinical as well as psychological, social, and behavioral factors to promote
      healthy pregnancy. Results have implications for design of sustainable prenatal
      services that might contribute to reduction of racial disparities in adverse
      perinatal outcomes.

PMID- 14672487
TI  - Pregnancy outcome after loop electrosurgical excision procedure: a systematic
      review.
AB  - OBJECTIVE: To examine the association of loop electrosurgical excision procedure
      (LEEP) and subsequent pregnancy outcomes. DATA SOURCES: A computerized search of
      MEDLINE and PubMed was conducted using the keys words "pregnancy" and "loop
      electrosurgical excision procedure," "LEEP," "LETZ," "LLETZ," or "loop excision."
      References from identified publications were manually searched and cross
      referenced to identify additional relevant articles. METHODS OF STUDY SELECTION:
      Studies were included that compared women who had had LEEP to women who had not
      had the procedure and that reported on subsequent pregnancy outcomes. Studies
      were excluded if there was no control group, if the LEEP was performed during the
      pregnancy, or if only an abstract was available. Five of 36 articles identified
      met the criteria for systematic review. TABULATION, INTEGRATION, AND RESULTS:
      Women who had had LEEP were more likely to have preterm birth (odds ratio [OR]
      1.81, 95% confidence interval [CI] 1.18, 2.76; P = .006) and low birth weight
      infants (<2500 g) (OR 1.60, 95% CI 1.01, 2.52; P = .04), but there was no
      difference in cesarean delivery, precipitous labor, labor induction, or neonatal
      intensive care unit admission. A subgroup analysis including only studies
      matching for smoking status revealed that preterm birth was still more common in
      women who had had LEEP (OR 2.53, 95% CI 1.42, 4.49; P = .001), but birth weight
      under 2500 g was no longer significantly different. CONCLUSION: LEEP appears to
      be associated with subsequent preterm birth, even when smoking status is matched.
      Studies with adequate sample size are needed to further evaluate the relationship
      of LEEP and preterm birth, controlling for potential confounders, including depth
      of the tissue sample.

PMID- 14672488
TI  - Traction suture of the cervix: a novel procedure with loop electrosurgical
      excision.
AB  - BACKGROUND: Loop electosurgical excision procedure (LEEP) of the transformation
      zone has become the preferred treatment of cervical intraepithelial neoplasia
      (CIN). CASE: An inadvertent vesicovaginal laceration occurred during LEEP of CIN2
      in a 57-year-old-woman with a cystocele. We developed a traction suture of the
      cervix that we used during LEEP that permits manipulation of the cervix outward,
      away from the nearby protruding tissues. CONCLUSION: Traction suture during LEEP
      may reduce inadvertent lacerations in patients with cystocele, rectocele, and
      other protruding tissues.

PMID- 14672489
TI  - First-trimester sonographic screening for Down syndrome.
AB  - Screening for Down syndrome is an important part of routine antenatal care. The
      most common screening method in the United States involves the assessment of a
      combination of factors: maternal age, multiple second-trimester serum markers,
      and second-trimester ultrasonography (as a so-called "genetic sonogram"). More
      recently, however, there has been significant interest in first-trimester methods
      of screening, including screening for first-trimester serum markers and the
      sonographic measurement of fetal nuchal translucency. Multiple studies have
      demonstrated that fetal nuchal translucency has the potential of being a very
      powerful predictor of fetal aneuploidy. However, for clinicians a large void
      remains between this knowledge and the practical issues that must be addressed
      prior to endorsing this form of screening for widespread use. This article
      provides an objective assessment of the literature describing nuchal
      translucency, as well as some adjunct first-trimester sonographic techniques,
      such as ductus venosus flow and nasal bone studies. Additionally, a detailed
      description of practical problems that might limit the implementation of this
      form of screening is presented.

PMID- 14672490
TI  - Is there an obstetric July phenomenon?
AB  - OBJECTIVE: To estimate whether variations in intrapartum management and
      complications exist with regard to the time of delivery within the academic year.
      METHODS: The delivery records of 7814 patients were separated by both term half
      year and quarter. Statistical comparisons were made using chi2 tests of
      association (P < .05) with respect to the academic time of the year and perineal
      trauma (third- or fourth-degree tear), episiotomy usage, cesarean delivery,
      postpartum hemorrhage, chorioamnionitis, shoulder dystocia, neonatal intensive
      care unit admission, 1- or 5-minute Apgar scores less than 7, and low umbilical
      cord pH. RESULTS: There were 4082 deliveries in the first half and 3732 in the
      second half of the year from April 1996 through March 1999. The first half-year
      overall cesarean rate was higher (15.8% versus 14.3%, P < .03). Primary cesarean
      rates were similar. No other differences were found by term half year. More
      perineal trauma was noted in the fourth quarter (first 3.3%, second 4.5%, third
      3.7%, fourth 5.5%, P < .037). Episiotomy usage was higher in both the first and
      fourth quarters (13.0%, 11.3%, 10.6%, and 14.8%, P < .002). More cases of
      chorioamnionitis occurred in the fourth quarter (first 3.4%, second 3.1%, third
      2.6%, fourth 4.0%, P < .038, third versus fourth quarter). Chorioamnionitis
      occurred more frequently in July (July 5.0% versus August-June 3.1%, P < .005).
      There were no other clinically significant differences. Neonatal outcomes were
      not affected by academic time of year. CONCLUSION: Although small differences in
      outcome exist with respect to the academic time of the year, the timing of these
      differences indicates that there is not a "July phenomenon" in obstetrics at our
      institution.

PMID- 14672491
TI  - Patient rotation and resolution of unilateral cornual obstruction during
      hysterosalpingography.

PMID- 14672492
TI  - A randomized controlled trial of prophylactic maneuvers to reduce head-to-body
      delivery time in patients at risk for shoulder dystocia.

PMID- 14672493
TI  - ACOG Practice Bulletin. Cervical insufficiency.

PMID- 14672494
TI  - ACOG Committee Opinion. Surgery and patient choice: the ethics of decision
      making.
AB  - The purpose of this Committee Opinion is to provide the obstetrician-gynecologist
      with an approach to decision making based on ethics in an environment of
      increased patient information, recognition of patient autonomy, direct-to
      consumer marketing, and many alternative or investigational treatments. A process
      for ethical decision making in surgery is discussed, illustrated by an example of
      elective cesarean delivery.

PMID- 14672495
TI  - ACOG Committee Opinion. Ethical considerations in research involving women.
AB  - In this Committee Opinion, the American College of Obstetricians and
      Gynecologists Committee on Ethics affirms both the need for women to serve as
      research participants and the obligation for researchers, institutional review
      boards, and others reviewing clinical research to evaluate the potential effect
      of proposed research on women of childbearing potential, pregnant women, and the
      developing fetus.

PMID- 14672496
TI  - ACOG Committee Opinion. Use of progesterone to reduce preterm birth.
AB  - Preterm birth affects 12% of all births in the United States. Recent studies
      support the hypothesis that progesterone supplementation reduces preterm birth in
      a select group of women (ie, those with a prior spontaneous birth at <37 weeks of
      gestation). Despite the apparent benefits of progesterone in this high-risk
      population, the ideal progesterone formulation is unknown. The American College
      of Obstetricians and Gynecologists Committee on Obstetric Practice believes that
      further studies are needed to evaluate the use of progesterone in patients with
      other high-risk obstetric factors, such as multiple gestations, short cervical
      length, or positive test results for cervicovaginal fetal fibronectin. When
      progesterone is used, it is important to restrict its use to only women with a
      documented history of a previous spontaneous birth at less than 37 weeks of
      gestation because unresolved issues remain, such as optimal route of drug
      delivery and long-term safety of the drug.

PMID- 14672497
TI  - ACOG Committee Opinion. Primary and preventive care: periodic assessments.
AB  - Periodic assessments provide an excellent opportunity for obstetricians and
      gynecologists to provide preventive screening, evaluation, and counseling. This
      Committee Opinion provides the recommendations of the American College of
      Obstetricians and Gynecologists' Committee on Gynecologic Practice for routine
      assessments in primary and preventive care for women based on age and risk
      factors.

PMID- 14672498
TI  - Supervision practices in allied mental health: relationships of supervision
      characteristics to perceived impact and job satisfaction.
AB  - This study examined whether supervision characteristics impacted on mental health
      practice and morale, and developed a new Supervision Attitude Scale (SAS).
      Telephone surveys were conducted with a representative sample of 272 staff from
      public mental health services across Queensland. Although supervision was widely
      received and positively rated, it had low average intensity, and assessment and
      training of skills was rarely incorporated. Perceived impact on practice was
      associated with acquisition of skills and positive attitudes to supervisors, but
      extent of supervision was related to impact only if it was from within the
      profession. Intention to resign was unrelated to extent of supervision, but was
      associated with positive attitudes to supervisors, accessibility, high impact,
      and empathy or praise in supervision sessions. The SAS had high internal
      consistency, and its intercorrelations were consistent with it being a measure of
      relationship positivity. The study supported the role of supervision in retention
      and in improving practice. It also highlighted supervision characteristics that
      might be targeted in training, and provided preliminary data on a new measure.

PMID- 14672499
TI  - Effects of racial match on Asian American mental health consumer satisfaction.
AB  - This study investigated the effects of consumer-provider racial match on consumer
      service satisfaction and treatment outcomes (i.e., Client Satisfaction
      Questionnaire and GAF-Posttest) of 96 outpatient consumers, 66 of whom were
      adults and 30 of whom were parent/caregivers of child consumers. Data was
      obtained by telephone interviews over a 6-week period. After controlling for four
      other variables, client satisfaction was higher for racially matched consumers.
      Racially matched child consumers also had higher GAF-Posttest scores.
      Implications of these findings are discussed.

PMID- 14672500
TI  - CONNECT: a measure of continuity of care in mental health services.
AB  - This paper introduces a measure of continuity of care (CONNECT) developed for
      mental health services research. CONNECT addresses qualities of interpersonal
      interaction in service-user/practitioner relationships through 13 scales and one
      single-item indicator. The scales are grouped into five domains: knowledge,
      flexibility, availability, coordination, and transitions. Domains were derived
      from ethnographic data. Service users rate responses to items using 5-point
      scales The measure is administered in interview format. CONNECT was developed for
      use with persons who have serious mental illness. Preliminary testing included
      cognitive interviews and two pilot studies. The results of a field test in which
      400 persons with serious mental illness completed CONNECT indicate that the
      measure is easily administered and produces well-distributed responses. Five
      scales meet the .80 criterion for internal-consistency reliability for group
      level research. Estimates of 2-week test-retest reliability indicate fair-to-good
      agreement. A broad initial validation strategy including known groups and
      convergent validity assessments produced results that will inform and focus
      future efforts. Next steps in the measure development process are discussed.

PMID- 14672501
TI  - Transportability of multisystemic therapy: evidence for multilevel influences.
AB  - This study examines factors associated with the implementation and short-term
      outcomes in dissemination sites of Multisystemic Therapy (MST), an intensive,
      short-term, family- and community-based treatment for serious antisocial behavior
      in youth. Participants were 666 children and families served by 217 therapists in
      39 sites. Pre- (T1) to immediate posttreatment (T2) differences in child problems
      and functioning were similar in magnitude to those found in randomized trials of
      MST. Results of random effects regression supported direct effects of therapist
      adherence, organizational climate, and structure at baseline on immediate
      posttreatment child outcomes. However, organizational factors were unrelated to
      adherence; thus, a hypothesized mediation model in which organizational climate
      and structure affect outcomes through therapist adherence to MST was not
      supported. Furthermore, the direction of associations between some organizational
      climate variables and outcomes countered expectations. Post hoc moderation
      analyses clarify these findings, with organizational effects differing by level
      of therapist adherence during treatment. Implications for the transfer of
      evidence-based psychosocial treatments for youth to usual care practice settings
      are discussed.

PMID- 14672502
TI  - Examination of treatment pattern differences by race.
AB  - Examine differences in treatment patterns among Blacks and non-Blacks in the U.S.
      Schizophrenia Care and Assessment Program. Baseline data from medical record
      abstraction, participant self-report and clinical assessment used to examine
      differences by race (race-gender pairings) (n = 2,239). Descriptive and
      multivariate (logistic) analysis employed. More Blacks were diagnosed with
      paranoid subtype. Blacks exhibited a more negative PANSS composite score, lower
      quality of life scores, and higher AIMS scores than non-Blacks. There was no
      statistically significant difference in the number of outpatient visits or
      inpatient admissions between Blacks and non-Blacks. Blacks had lower medication
      adherence and received less second-generation agents and more
      antiparkinson/anticholinergic agents. Proportion of Black males receiving depot
      was greater than other race-gender pairings. Regression results indicate Blacks
      more likely to be prescribed only first-generations after controlling for depot
      (OR = 1.64; CI = 1.27-2.12; p = 0.0002). Schizophrenia is, on average,
      accompanied by different diagnoses and symptoms in Blacks. Symptom profiles
      indicate that second-generation antipsychotics may be underprescribed to Black
      patients.

PMID- 14672503
TI  - Brain weight: what does it mean?
AB  - The weights of the whole and various parts of 8 unfixed normal adult brains were
      determined at autopsy, and the relative weight of each part as compared with the
      total brain weight was calculated. On the average, the cerebrum accounted for 87%
      of the total brain weight, the cerebellum and brain stem for 13%, whereas the
      contribution of the attached upper spinal cord was negligible (< 2 g). The
      removed leptomeninges had a mean weight of 34.2 g (2.5% of the total brain
      weight), but they may reach 50 g. The slices of the cerebrum with removed
      leptomeninges weighed only 79.2 - 84.4% of the total brain weight. It is
      concluded that all scientific papers reporting brain weights should state whether
      the recordings are based upon fresh or fixed specimens and, in the latter case,
      the fixation procedures must be described accurately. Furthermore, it is of equal
      importance to indicate exactly the anatomic structures that have been weighed.

PMID- 14672504
TI  - DNA ploidy and nuclear morphometry in adult intracranial ependymomas.
AB  - The identification of prognostic parameters in ependymomas remains an important
      but controversial issue in particular to the significance of histopathological
      features. Intracranial location is a rare presentation for adult ependymomas. DNA
      ploidy status and nuclear morphometric features of ependymomas are not well
      established. We retrospectively studied the clinicopathologic features of 12
      adult intracranial ependymomas and performed image cytometric DNA analysis with
      nuclear morphometry. The overall survival rate was 75%. Two cases were anaplastic
      ependymomas. Statistically, histology failed to demonstrate a correlation with
      clinical outcome or overall survival. DNA ploidy (p = 0.033), DNA index (p =
      0.016) and 5c exceeding rate (p = 0.017) were statistically correlated with
      clinical outcome, but not correlated with overall survival. Nuclear morphometric
      features measured using 3 different data selection methods were not correlated
      with clinical outcome or overall survival. It is difficult to identify prognostic
      factors in a series of cases with limited number. The problem is complicated by
      the fact that the common criteria used for recognizing malignancy in gliomas are
      not completely reliable in ependymomas. Nuclear morphometric findings support the
      general impression that ependymomas are morphologically highly variable tumors.
      In spite of the small sample size of our series and other factors influencing
      survival such as the extent of resection and malignant histology, aneuploidy can
      be suggested as a promising factor, which may reflect potential aggressiveness of
      the tumor in adult intracranial ependymomas.

PMID- 14672505
TI  - Nitric oxide synthase expression and enzymatic activity in human brain tumors.
AB  - Nitric oxide (NO) is synthesized by NO synthases (NOS), existing in 3 isoforms.
      NO influences a great variety of vital functions including vascular tone and
      neurotransmission. Under conditions of excessive formation, NO emerges as an
      important mediator of neurotoxicity in a variety of disorders of the central
      nervous system (CNS). Inhibitors of NOS are available that may modify the
      activity of all isoforms, which may be of clinical relevance. The expression of
      the 3 NOS isoforms nNOS, iNOS and eNOS and NOS enzymatic activity was examined in
      40 patients with primary CNS tumors (gliomas WHO grades I - IV and meningeomas
      WHO grades I - III) and in 13 patients with metastases from adenocarcinomas or
      malignant melanomas. A polyclonal antibody directed against nNOS and monoclonal
      antibodies directed against iNOS and eNOS were used for immunohistochemical
      staining. NOS enzymatic activity, measured by labeled arginine to citrulline
      conversion, was assessed in tissue specimens obtained from the same tumors. NOS
      data were compared with clinical variables and the degree of edema as judged from
      MR scanning. nNOS expression was increased in tumor cells of glial neoplasms and
      most pronounced in high-grade tumors, WHO grades III and IV, and in the carcinoma
      and melanoma metastases. Low-grade gliomas, WHO grades I and II and meningeomas
      expressed no or only little nNOS. iNOS was only expressed in a few tumors. eNOS
      was expressed sporadically in the tumor cells while the expression was increased
      in vascular endothelial cells in both the tumor itself and the peritumoral area
      of glial neoplasms, and in metastases. eNOS expression was sporadic in
      endothelial cells of meningeomas. NOS enzymatic activities were heterogeneous
      among tumor types (0 - 13.8 pmol/min/mg of protein) without correlation to the
      NOS expression found by immunohistochemical techniques. Likewise, NOS activity
      and expression was not correlated to the clinical scores or brain edema. In
      conclusion, nNOS expression may be a putative useful indicator of brain tumor
      differentiation and malignancy. The enhanced expression of eNOS in vascular
      endothelial cells of glial neoplasms and metastases raises the possibility that
      NO production in tumor endothelial cells may contribute to tumor blood flow
      regulation and possibly brain edema.

PMID- 14672506
TI  - Hematological neoplasms with first presentation as spinal cord compression
      syndromes: a 10-year retrospective series and review of the literature.
AB  - CONTEXT: The epidural space is a well-known, albeit uncommon, location for
      lymphomatous involvement, estimated to occur in less than 3% of all systemic
      lymphomas. Initial presentation of the patient with disease in this site (i.e.
      primary spinal epidural lymphoma) has been considered to be "rare". When it has
      been reported, many studies have emphasized the occurrence of aggressive
      lymphomas with a poor prognosis. DESIGN: A 10-year retrospective search of our
      files generated 7 patients who presented initially with back pain, incontinence
      and/or lower extremity weakness, and by neuroimaging studies were found to have
      masses causing spinal cord compression syndromes necessitating neurosurgical
      intervention. RESULTS: The 7 patients included 4 males and 3 females with
      thoracic and lumbar epidural masses. Tumor types included high-grade non-Hodgkin
      lymphoma, B cell type (n = 4), indolent B cell lymphoma (n = 1), nodular
      sclerosing Hodgkin lymphoma (n = 1) and plasmacytoma (n = 1). Advanced disease
      (stage 4) was subsequently identified in all 7 patients. Despite this, survival
      varied greatly with therapy, from 3 weeks to almost 6 years, underscoring the
      need for correct classification of the lymphoma in order to optimize
      chemotherapeutic choices. The epidural space was the site of presentation of
      disease in 4% of all lymphomas diagnosed at our institution. CONCLUSIONS:
      Combining all reports in the literature, epidural presentation of lymphoma is not
      rare. Epidural lymphomas are distinct from both primary central nervous system
      lymphomas and from primary dural lymphomas. A broad range of systemic
      hematological tumor types can present as epidural masses. A full work-up for
      lymphoma classification may only be possible from the tissues received at the
      time of the neurosurgical decompression or biopsy procedure.

PMID- 14672507
TI  - Anomalies of cerebral structures in acranial neonates.
AB  - Eleven cases of newborns with acrania and macroscopically diagnosed anencephaly
      were neuropathologically examined. They presented changes in which 1 group
      corresponded to the diagnosis of aprosencephaly. In the second group, the
      development of prosencephalic structures was more advanced. The pathomechanism of
      the observed anomalies was analyzed in relation to data provided by molecular
      genetic classification of nervous system malformations, but that did not exclude
      the influence of eventual extrinsic factors.

PMID- 14672508
TI  - Atypical late-onset dementia characterized by limbic degeneration with coiled
      bodies and argyrophilic threads.
AB  - This report concerns an autopsy case of late-onset dementia with atypical
      neuropathological features. The patient was a Japanese man who was 83 years old
      at the age of death. At 73 years, he developed behavioral disorders, including
      emotional changes, and dementia. He died at the age of 83. A neuropathological
      study revealed largely confined involvement of the limbic regions, characterized
      by degeneration consisting of neuronal loss with a spongy state and gliosis.
      Massive tau-positive oligodendroglial coiled bodies and argyrophilic threads were
      also observed mainly in these regions. Although the clinicopathological findings
      of the present case showed some similarities to those of a unique subtype of
      frontotemporal dementia, including mesolimbocortical dementia, argyrophilic grain
      disease, corticobasal degeneration and dementia with tangles, there seems to be
      no suitable category of neurodegenerative disease into which our case can be
      classified. Further study is needed to determine whether the present case could
      be classified as an atypical case of these diseases or represents a new entity.

PMID- 14672509
TI  - Concurrence of multiple sclerosis and intracranial glioma. Report of a case and
      review of the literature.
AB  - We report a 39-year-old female patient known to have multiple sclerosis (MS), who
      later developed cerebral glioblastoma. The tumor was documented on the brain
      magnetic resonance imaging (MRI) during the work-up for an apparent relapsing MS,
      and was subsequently confirmed pathologically by stereotactic biopsy and the
      postmortem brain examination. Our case, as well as others, re-emphasizes the need
      to evaluate the symptoms and brain MRI carefully, even in well-documented MS
      subjects. The concurrence of MS and intracranial glioma is uncommon. The possible
      relationship between the 2 diseases was discussed, and related literature
      reviewed.

PMID- 14672510
TI  - A comparative study of adults with and without self-reported learning
      disabilities in six English-speaking populations: what have we learned?
AB  - The purpose of this study was to compare adults with and without self-reported
      learning disabilities (SRLD and NSRLD) from six English-speaking populations
      including: English-speaking Canada, Great Britain, The Republic of Ireland, New
      Zealand, Northern Ireland, and the United States. These six populations were
      selected because they were all English-speaking populations, participated in the
      first administration of the International Adult Literacy Survey (IALS), and
      included the optional questions regarding the presence of a disability. In this
      study, we compared the groups on prevalence by population, percentage of each
      group by age and gender, awareness of learning disabilities and problems in
      school, document and quantitative literacy proficiency, educational attainment,
      reasons for dropping out of school, and employment, occupational and financial
      status. Findings were reported among these six populations within an historical
      perspective including differences in awareness and definition of learning
      disabilities, public policy, special education services, reading pedagogy, and
      teacher preparation. Recommendations are made for improving literacy and long
      term outcomes for those with learning disabilities in all nations as well as
      future research directions.

PMID- 14672511
TI  - Adults with self-reported learning disabilities in Slovenia: findings from the
      international adult literacy survey on the incidence and correlates of learning
      disabilities in Slovenia.
AB  - This study of adults with self-reported learning disabilities (SRLD) in Slovenia
      is part of a larger secondary analysis of the data from the International
      Literacy Survey project (IALS). The purpose of the study was to examine the
      characteristics of 79 (2.68%) individuals who reported experiencing learning
      disabilities and compare them to the general population on a variety of
      indicators of educational background, employment status, and reading and writing
      activities at work and at home. The proficiency scores of the SRLD individuals
      were lower in all three literacy domains (prose, document and quantitative
      literacy). In prose literacy 77.9% of SRLD adults performed at Level 1 and only
      7.8% reached the level necessary for a modern technological society. Experiencing
      learning disabilities was not related to gender or age, however, results showed
      significant differences between the levels achieved by older and younger people
      with SRLD. In SRLD groups aged 40 years and above, no one achieved more than the
      second level of literacy in any domain. Learning disabilities were reported more
      frequently in rural areas. SRLD groups achieve significantly lower educational
      attainment, and lower employment status, with a preference for manual labour or
      craft. These findings are of critical importance. SRLD people report that poorer
      literacy skills are an obstacle to their progression in employment. In the
      Slovene sample, the SRLD group stands out for low scores in quantitative
      literacy. Results show that they are less active, pick up information only
      auditorily or in short written form. They need more frequent help from relatives
      in literacy activities. Interpretation of the IALS data on SRLD presents many
      problems. These include amongst others, problems in terminology, different
      background factors, and the validity of self-report measures. However, the study
      also raises many interesting challenges for future research and policy.
      Increasing the availability of support, assistance and counselling for
      adolescents and adults with learning disabilities remains a very important goal
      for dyslexia and LD policies in Slovenia.

PMID- 14672512
TI  - Adults with learning disabilities: differences between The Netherlands and
      Flanders.
AB  - In this paper, similarities and differences are outlined between adults with self
      reported learning disabilities (SRLD) drawn from the International Adult Literacy
      Survey (IALS) data on adult literacy in The Netherlands and Flanders. These
      results are discussed in terms of striking differences in the educational context
      within which the adults developed. The literacy skills of SRLD adults in The
      Netherlands are superior to SRLD adults in Flanders. This is interpreted in terms
      of societal acceptance of disability.

PMID- 14672513
TI  - Copper hypersensitivity: dermatologic aspects--an overview.
AB  - Reports of immune hypersensitivity reactions of both the immediate and the
      delayed type following cutaneous or systemic exposure to copper are reviewed here
      in an endeavor to draw a comprehensive profile of the immunogenic potential of
      that metal and its compounds. The immunotoxic potential of the metal is also
      briefly reviewed. In principle, as noted for other transition metals, the
      electropositive copper ion is potentially immunogenic because of its ability to
      diffuse through biological membranes, forming complexes when in contact with
      tissue protein. Based on the results of the predictive guinea pig test and the
      local lymph node assay (LLNA), copper has a low sensitization potential. Reports
      of immune reactions to copper include immunologic contact urticaria (ICU),
      allergic contact dermatitis (ACD), systemic allergic reactions (SAR) and contact
      stomatitis (STO), but considering the widespread use of copper intrauterine
      devices (IUDs) and the importance of copper in coinage, items of personal
      adornment and industry, unambiguous reports of sensitization to the metal are
      extremely rare, and even fewer are the cases that appear clinically relevant.
      Most reports of immune reactions to copper describe systemic exposure as a cause-
      predominantly to intrauterine devices and to prosthetic materials in dentistry-
      implicitly excluding the induction of hypersensitivity from contact with the skin
      as a risk factor.

PMID- 14672514
TI  - Evaluation criteria for aircraft noise.
AB  - Based on extensive and detailed reviews the present paper suggests evaluation
      limits for aircraft noise for the prediction of noise effects and for the
      protection of residents living in the vicinity of (newly constructed or extended)
      civil airports. The protection concept provides graded assessment values:
      Critical Limits indicate noise loads that shall be tolerated only exceptionally
      during a limited time. Protection Guides are central assessment values for taking
      actions to reduce noise imission. Threshold values inform about measurable
      physiological and psychological reactions due to noise exposures where long term
      adverse health effects are not expected. Evaluation limits are provided for
      various protection goals. Apart from hearing damage, evaluation limits are
      provided for the avoidance of primary extraaural effects on communication and on
      sleep, for the avoidance of annoyance as a secondary effect and for the avoidance
      of suspected cardiovascular diseases. Such limits enable authorities to outline
      the areas around airports, where appropriate measures are mandatory to protect
      residents against the deleterious effects of noise. Protecting residents is a
      dynamic process that must be followed up. The evaluation limits must be
      repeatedly tested in view of new scientific findings and adapted, if necessary.

PMID- 14672515
TI  - Environmental toxicology and health effects associated with dinitrotoluene
      exposure.
AB  - Dinitrotoluenes (DNTs) are nitroaromatic compounds appearing as pale yellow
      crystalline solids at room temperature. Dinitrotoluenes exist as a mixture of 2
      to 6 isomers, with 2,4-DNT, and 2,6-DNT being the most significant. About 500
      persons are estimated to be potentially exposed yearly to 2,4-DNT and 2,6-DNT
      during the production of munitions and explosives. The main route of human
      exposure at ammunition facilities is inhalation, but dermal contact and
      inadvertent ingestion can also be substantial. In factory workers, exposure to
      DNTs has been linked to many adverse health effects, including cyanosis, vertigo,
      headache, metallic taste, dyspnea, weakness and lassitude, loss of appetite,
      nausea, and vomiting. Other symptoms including pain or parasthesia in
      extremities, abdominal discomfort, tremors, paralysis, chest pain, and
      unconsciousness have also been reported. The primary targets of DNT toxicity are
      the hematopoietic system (pallor, cyanosis, anemia, and leukocytosis), the
      cardiovascular system (ischemic heart disease), the nervous system (muscular
      weakness, headache, dizziness, nausea, insomnia, and tingling pains in the
      extremities) and the reproductive system (reduction of sperm counts, alteration
      of sperm morphology, and aspermatogenesis). An association between DNT exposure
      and increased risk of hepatocellular carcinomas and subcutaneous tumors in rats,
      as well as renal tumors in mice, has been established. Epidemiologic studies of
      DNT toxicity have been limited to small groups of workers who had been
      occupationally exposed at various ammunitions production facilities. Clearly
      defining the health effects of DNTs with a high degree of confidence has
      therefore been difficult because of the multigenic nature of occupational
      exposure. In an attempt to update the toxicologic profile of the DNTs, we hereby
      provide a critical review of the environmental and toxicologic pathology of DNTs,
      with a special emphasis on their potential implications for public health.

PMID- 14672516
TI  - Pharmacogenomics and "individualized drug therapy": high expectations and
      disappointing achievements.
AB  - Since 1965 there have been more than 800 pharmacogenetics/genomics reviews - most
      suggesting that we are on the verge of offering individualized drug therapy to
      everyone. However, there are numerous reasons why this approach will be extremely
      difficult to achieve in the foreseeable future. Drug treatment outcome represents
      a complex phenotype, encoded by dozens, if not hundreds, of genes, and affected
      by many environmental factors; therefore, we will almost always see a gradient of
      response. Phenotyping assays of blood enzyme activities (if feasible) are
      generally more successful than DNA genotyping for predicting unequivocal outcomes
      of drug therapy in each and every patient. Phenotyping with probe drugs has
      generally not succeeded, because of the overlapping substrate specificities not
      only of drug-metabolizing enzymes but also transporters, receptors, ion channels,
      transcription factors, and other drug targets; drug-drug interactions, enzyme
      induction and inhibition, and multiple (enzyme, transporter, second-messenger,
      signal transduction) pathways also present enormous problems. Genotyping to
      predict drug disposition, efficacy, toxicity, and clinical outcome has been
      proposed, but the success of genotyping in individualized drug therapy currently
      appears unlikely because of the many shortcomings (frequency of DNA variant
      sites, ethnic differences, admixture) and complexities (plasticity of the genome,
      multiple mechanisms for determining sizes and locations of haplotype blocks) of
      this approach. Genomics is an important tool in basic research; yet, it is
      unrealistic to include genotyping within the realm of tests available to the
      practicing clinician in the foreseeable future. The same can be said for
      transcriptomics and proteomics, which also rely on available sources (tumors,
      biopsies, excreta). The newly emerging fields of metabonomics and phenomics might
      offer solutions to anticipating and decreasing individual risk for adverse drug
      reactions in each individual patient; however, tests based on these approaches
      are not expected to become available to the practicing clinician for at least the
      next 5-10 years.

PMID- 14672517
TI  - A perspective on progress in pharmacogenomics.

PMID- 14672518
TI  - Rhetoric and hype: where's the 'ethics' in pharmacogenomics?
AB  - There is increasing discussion in public and academic forums about the
      anticipated benefits of pharmacogenomics, as well as the attendant social and
      ethical implications of this research. Yet there is often an implicit assumption
      that the benefits of pharmacogenomics are 'just around the corner' and will
      significantly outweigh the costs. Furthermore, it is argued that the associated
      ethical issues are not as profound as those that emerge in other areas of
      genetics, and that experience gained wrestling with these other issues provides
      ample ethical and regulatory tools to deal with any problems arising with
      pharmacogenomics. We contend that this vision of ethical and social issues
      associated with pharmacogenomics is not so clear-cut. The scientific evidence is
      more complex and contested than the public, academics, and policy makers, have
      been led to believe, and while there may be real clinical benefits from this
      research, they are not likely to arrive in the near future. Pharmacogenomics
      research is also occurring in a terrain occupied by a multitude of different and
      powerful actors, with diverse and often competing interests. It is therefore
      essential to investigate the broader social and political context, unravel the
      various interests pressuring for early implementation, and deconstruct the hype
      in order to appreciate a fuller range of ethical and social consequences
      associated with the current developments of pharmacogenomics.

PMID- 14672519
TI  - Race, distributive justice and the promise of pharmacogenomics: ethical
      considerations.
AB  - Pharmacogenomics has emerged in the popular press as a key vehicle ushering in a
      new era of personalized medicine. Often described in utopian terms, gene
      sequencing technology is predicted to result in the creation of a new line of
      therapeutics tailored to individual genetic signatures. In the absence of cost
      effective, ubiquitous genome scanning tests, it may be more accurate to describe
      the next wave of genomic medicine as population-based rather than one focused on
      individual differences. Although the completion of the Human Genome Project
      seemed to confirm the fallacy of a genetic basis of 'race', the use of race in
      understanding human genetic variation has become a central focal point in the
      development of tools in genomic research in medicine. Despite the often repeated
      statement that humans share 99.9% of their genetic makeup, the growing number of
      privately and publicly funded cell repositories collecting DNA samples from
      racially identified populations reflects the increasing salience of the
      relationship between race and genes. Research on the ethical implications of
      identifying race in pharmacogenomics research has thus far, been fairly limited.
      As the field surges ahead, it is critical to examine the use of race in
      pharmacogenomics research and its attendant benefits and potential harm to
      individuals and groups.

PMID- 14672520
TI  - Impact of pharmacogenomics on neglected diseases of the developing world.
AB  - Pharmacogenomics promises to have an important impact on the major health
      problems of the developing world, especially on neglected infectious diseases
      such as malaria, tuberculosis, and HIV/AIDS. Its capacity to identify new targets
      for drug development, together with its potential application in identifying
      populations who will respond favorably to a particular drug, gives it a unique
      place as a technology to bridge the genomics divide between rich and poor
      nations. To realize its true potential, however, significant scientific, legal,
      ethical, political, and economic challenges need to be overcome. For this to
      occur, an innovative global approach based on strong collaboration between
      industry, academia, non-governmental, and international organizations will be
      required. Simultaneously, more equitable and active participation from developing
      country researchers themselves is critical in overcoming these challenges.

PMID- 14672521
TI  - Pharmacogenomics and children: meeting the ethical challenges.
AB  - Pharmacogenomic research promises to permit the development and delivery of safer
      and more effective drugs. If children are to receive these benefits, as justice
      would demand that they should, children must be included in trials that assess
      the impact of genetic variation, changing patterns of gene expression over time,
      and the effects of administering drugs. The ethical and legal challenges to
      conducting the necessary research include concerns about vulnerability and issues
      of consent, the scientific validity of the studies and the larger policy question
      of priority setting. Proposed strategies for ensuring the appropriate conduct of
      this research include analysis of the ethics based on risks and harms rather than
      presence or absence of a disorder, the development of model substrates to conduct
      physiological testing more safely, and the consideration of the disposition and
      impact of individual study results. With appropriate study, ultimately the use of
      pharmacogenomic testing can become available for children in the clinical
      setting.

PMID- 14672522
TI  - Policy before practice: genetic discrimination reviewed.
AB  - The value of genetics in medicine has been steadily developing with our
      increasing knowledge of the human genome. Genetic testing to determine disease
      risk or potential drug effects is set to become more commonplace. With this comes
      increasing concern about access to genetic information, and the potential for
      discriminatory usage of such information. At present, the scope and
      predictability of genetic testing and the conclusions that may be drawn fairly
      from genetic information are limited. Nonetheless, public concerns about
      discrimination based on the possession of a genetic trait or condition are well
      documented. The prospect that such information might be used in decisions
      regarding employment or insurability has caused anxiety and prompted legislation
      largely dedicated to the use of information about one's genotype rather than
      medical information in general. These laws emphasize genetic information as
      distinct from other medical information and attempt to prioritize interests in
      genetic information. As the distinction between genetic and medical information
      becomes untenable, those who would regulate the use of genotypic information will
      find this approach to policy problematic.In considering the limits of legislation
      as an effective tool of regulating genetic discrimination, several conclusions
      can be drawn: firstly, despite the promise of genomic medicine, current knowledge
      is insufficient to justify the use or application of certain genetic information
      in nonmedical contexts; secondly, public resistance to genomic medicine that is
      based on fear of genetic discrimination poses a danger that justifies a policy
      response; and thirdly, such a response may be purely symbolic and not entirely
      effective, provided that the policy establishes a consensus regarding the
      applicability of genetic information in nonmedical contexts.

PMID- 14672523
TI  - Surgical treatment of stage I non-small cell lung carcinoma.
AB  - In stage I non-small cell lung cancer (NSCLC), the cancer is localized to the
      lung. For this early stage NSCLC, therefore, surgery is considered to be the
      treatment of choice. In this report, we reviewed the surgical treatment
      approaches for stage I NSCLC, placing emphasis on limited resection and video
      assisted thoracic surgery (VATS). In regard to limited resection, sublobar
      resection (wedge resection and segmentectomy) may yield a good long-term outcome
      in selected cases, as does lobectomy. No strong evidence to recommend this
      procedure has, however, been published. On the other hand, many descriptive
      studies have indicated that VATS may be useful for the treatment of NSCLC,
      although the results have not shown any statistically significant differences
      from those of resection by conventional open thoracotomy. In addition to the low
      invasiveness, the curability of NSCLC using the VATS approach has been recognized
      to be similar to that of the standard thoracotomic approaches in clinical
      practice. Well-controlled studies with strong statistical results are needed to
      provide strong supportive evidence for the use of VATS for NSCLC. (Ann Thorac
      Cardiovasc Surg 2003; 9: 283-9)

PMID- 14672524
TI  - "The Law of 3": prognostic parameters for resected metastatic pulmonary tumors.
AB  - Metastatic tumors from various organs are found in pulmonary tissue because of
      the unique anatomical function of the lungs as a filter for systemic venous
      return. A retrospective study of the clinical factors used to assess the
      prognosis of 80 patients who underwent resections of metastatic pulmonary tumors
      in our surgical department between September 1978 and December 2002 is presented.
      The overall 5-year survival rate in our study was 31.7%. We demonstrated four
      significant factors used in predicting the prognosis of patients with resected
      metastatic pulmonary tumors: diameter of the tumor (</=3.0 cm or >3.0 cm), number
      of tumors (</=3 or >3), disease-free interval (>/=3 years or <3 years), and ratio
      of the diameter of the largest tumor to the diameter of the smallest tumor in
      patients with multiple metastases (</=3 or >3). Based on our results, we have
      applied the term "the law of 3" to these valuable prognostic factors. Among these
      parameters, the ratio of the diameter of the largest to the diameter of the
      smallest tumor may be applicable as a new prognostic parameter for surgery in
      patients with multiple foci. (Ann Thorac Cardiovasc Surg 2003; 9: 290-4)

PMID- 14672525
TI  - Significance of expression of TGF-beta in pulmonary metastasis in non-small cell
      lung cancer tissues.
AB  - Recent studies have evaluated the cytokine network involved in the local immune
      response to tumors. In addition to infiltrating inflammatory cells, tumors also
      produce cytokines and growth factors that may alter tumor growth and tumor
      immunogenicity. Ninety-one samples of NSCLC were used in this study. We measured
      the expression of VEGF, TNF-alpha, TGF-beta, IL-6, IL-8, IL-12, INF-gamma, and
      MCP-1 in NSCLC tissues, by ELISA. The expression of IL-6 and IL-8 were
      significantly higher in squamous cell carcinoma than in adenocarcinoma (p=0.016
      and p<0.001, respectively). The expression of TGF-beta, MCP-1 and IL-8 were
      significantly higher in pulmonary metastasis positive than negative cases
      (p=0.002, p=0.001, and p=0.008, respectively). In multivariate logistic
      regression analysis, the expression of TGF-beta was an independent risk factor
      for the occurrence of pulmonary metastasis (p=0.008, 95% CI=1.002-1.011). We
      confirmed that tumor infiltrating stromal cells were major sources of TGF-beta by
      immunohistochemical analysis. The expression of VEGF and IL-8 were significantly
      higher in cases with central necrosis (p=0.006 and p=0.011, respectively). We
      speculated that TGF-beta expression in tumor infiltrating stromal cells may
      regulate the occurrence of spontaneous pulmonary metastasis in NSCLC. (Ann Thorac
      Cardiovasc Surg 2003; 9: 295-300)

PMID- 14672526
TI  - A study of the myocardial protective effect of rapid cooling based on
      intracellular Ca, intracellular pH, and HSP70.
AB  - OBJECTIVE: It has been reported that rapid cooling of the heart during
      normothermic coronary circulation at reperfusion after ischemia promotes early
      recovery of cardiac function due to the positive inotropic effects on the
      myocardium produced by cooling. The aim of the present study was to investigate
      the myocardial protective effect of rapid cooling by measuring heat shock protein
      (HSP) levels and examining the relationship between cardiac function,
      intracellular Ca concentration, and intracellular pH after rapid cooling.
      METHODS: Isolated perfused rat hearts were subjected to ischemia for 60 minutes
      at a myocardial temperature of 37 degrees C. One group of hearts (group R) was
      subjected to 3 minutes of rapid cooling (</=4 degrees C) 3 minutes after
      reperfusion was started. The other hearts (group C) were not cooled. Myocardial
      protection was then compared in the two groups by measuring heart rate, coronary
      flow, left ventricular contraction, intracellular Ca concentration (fura-2
      fluorescence), and intracellular pH (BCECF-AM fluorescence) and examining HSP70
      by western blot. RESULTS: (1) Left ventricular contraction was 105+/-0.05% of the
      pre-ischemia value in group R after rapid cooling, whereas recovery was poor in
      group C (63+/-2%). (2) The intracellular Ca concentration in group R rose to
      141+/-8% of the pre-ischemia value during ischemia, but decreased to 101+/-3% at
      reperfusion after rapid cooling. In group C, the Ca concentration was 144+/-4% of
      the pre-ischemia value during ischemia and rose further to 156+/-6% at
      reperfusion. (3) In group R, the intracellular pH was 6.85+/-0.05 during ischemia
      and rose after reperfusion was started, but after rapid cooling, decreased again
      to 7.43+/-0.02 after 60 minutes reperfusion. In group C, the pH was 6.88+/-0.06
      during ischemia and rose to 7.90+/-0.09 60 minutes after reperfusion was started.
      (4) HSP70 was detected in both groups, but the concentration (luminescence) was
      lower in group R than in group C. CONCLUSION: Rapid cooling reduces myocardial
      injury by preventing intracellular Ca overload at reperfusion via inhibition of
      the Na(+)/Ca(2+) exchanger and also decreases the appearance of HSPs, the so
      called homeostasis proteins. (Ann Thorac Cardiovasc Surg 2003; 9: 301-6)

PMID- 14672527
TI  - Effects of ischemic preconditioning on myocardial protective on cardiac surgery:
      possibility of ischemic preconditioning and adenosine administration.
AB  - SUBJECT: We evaluated the efficacy for concomitant use of ischemic
      preconditioning (IPC) and cardioplegic arrest with adenosine premedication on
      myocardial protection. METHODS: Twenty-one pigs were divided into three groups:
      1) control group, 2) IPC group which had IPC, 3) IPC+adenosine triphosphate (ATP)
      group which had an administration of 140 gamma of ATP (Adetphos, Kowa, Tokyo,
      Japan) during IPC. IPC was employed by 3 minutes of aortic cross clamping and 5
      minutes of reperfusion. After cardioplegic arrest, the hemodynamical state was
      observed during 60 minutes of reperfusion. Serum adenosine, troponin-T, E-max,
      and Tau (the time constant of early diastolic left ventricular pressure decay)
      were compared. RESULTS: Serum adenosine levels and at the end of IPC and 60
      minutes reperfusion were significantly higher in the IPC and IPC+ATP groups than
      the control group. Comparison of the myocardial contractile force indicator E-max
      showed that the IPC and IPC+ATP groups showed significantly higher recovery rates
      of myocardial contractile force than the control group. Tau was the lowest in the
      IPC+ATP group than the other groups. In the histopathological study, the control
      group showed widely distributed hypercontraction bands and waving degeneration of
      myofibrils. On the other hand, the structure of myofibrils was well preserved in
      the IPC and IPC+ATP groups. CONCLUSIONS: The concomitant use of IPC enhanced the
      effect of a myocardial protective solution. However, the administration of
      adenosine during IPC did not show any further advantage than IPC along. (Ann
      Thorac Cardiovasc Surg 2003; 9: 307-13)

PMID- 14672528
TI  - Descending aortic pulsed wave Doppler can predict changes in cardiac output
      during off-pump coronary artery bypass surgery.
AB  - Retraction and stabilization of the heart can induce rapid and large changes in
      the hemodynamic state during off-pump coronary artery bypass graft surgery
      (OPCABG). We aimed to determine if Doppler measurement of flow in the descending
      artery with transesophageal echocardiography (TEE) can provide a beat-to-beat
      assessment of changes in cardiac output (CO) in 26 OPCABG patients. Simultaneous
      measurements were performed of CO using thermodilution, and descending aortic
      flow (FlowDA) with TEE, prior to grafting, and during grafting to the left
      anterior descending artery (LAD), circumflex (Cx) and right coronary artery (RCA)
      territories. CO decreased from baseline (SD) values of 6.2 (1.7), to 5.4 (1.8)
      L/min during grafting to the LAD, 4.4 (1.5) L/min to the Cx territory, and 4.4
      (1.4) L/min to the RCA territory (P<0.001). There was poor correlation between CO
      and FlowDA between individuals. In a subgroup of 16 patients who had grafts to
      all territories, the changes in Flow(DA), occurred in the same direction and
      magnitude as changes in CO (P = 0.062, RM-ANOVA for factor*time interaction).
      Doppler assessment of flow in the descending aorta is able to track changes in CO
      during OPCABG. (Ann Thorac Cardiovasc Surg 2003; 9: 314-8)

PMID- 14672529
TI  - Multidisciplinary treatment by pneumonectomy, PMX and CHDF in a case of pulmonary
      suppuration complicated with septic shock.
AB  - A 68-year-old male, who had suffered from pulmonary tuberculosis with cavities on
      the right upper lobe, developed breathlessness, bloody sputum, right chest pain
      and fever. His laboratory data on admission showed severe infection or sepsis
      (WBC 2,600/mL, CRP 40.2 mg/dL), and his respiratory condition rapidly worsened.
      In the intensive care unit (ICU) he was given continuous hemodiafiltration
      (CHDF), but his respiratory condition failed to improve and it was therefore
      decided to perform a right pneumonectomy. His severe hypoxemia was resolved but
      because high dose catecholamines medication was still required, polymyxin-B
      immobilized fiber (PMX) and CHDF were performed. The operation was successful and
      he was transferred from the ICU to a general ward seven days postoperatively. The
      vicious circle of septic shock presenting in this case was successfully broken by
      the pneumonectomy and subsequent treatment by PMX and CHDF, which eliminated the
      causative factors of sepsis. (Ann Thorac Cardiovasc Surg 2003; 9: 319-22)

PMID- 14672530
TI  - Combined cox maze procedure, septal myectomy, and mitral valve replacement for
      severe hypertrophic obstructive cardiomyopathy complicated by chronic atrial
      fibrillation.
AB  - Atrial fibrillation (AF) has been reported to be an important prognostic
      indicator for clinical deterioration particularly in patients with hypertrophic
      obstructive cardiomyopathy (HOCM). A 66-year-old female complained of severe
      exertional dyspnea and tachycardia, which were resistant to medical treatments.
      Doppler echocardiography demonstrated a peak left ventricular outflow tract
      (LVOT) gradient of 117 mmHg at rest. A catheter examination revealed left
      ventricular end diastolic pressure of 34 mmHg, a cardiac index of 1.94
      L/minute/m(2), and a peak LVOT gradient of 70 mmHg at rest. A transaortic septal
      myotomy/myectomy was performed first, and Cox maze III procedure was performed
      through the right and left atrium followed by mitral valve replacement. The
      patient recovered dramatically except for temporary complete atrioventricular
      block. One year after operation, the patient is doing well with sinus rhythm and
      the echocardiogram revealed a peak LVOT pressure gradient of 7.6 mmHg at rest.
      This surgical approach might be recommended for the treatment of AF in HOCM. (Ann
      Thorac Cardiovasc Surg 2003; 9: 323-5)

PMID- 14672531
TI  - Multisaccular aneurysm developing in association with abdominal aortic
      coarctation: report of a surgical case.
AB  - This paper reports a rare case of a 65-year-old woman diagnosed with a
      multisaccular, abdominal aortic aneurysm (AAA), 35 mm in diameter, which was
      revealed developing just distal to an abdominal aortic coarctation (AAC), with a
      20 mmHg pressure gradient. The patient underwent corrective surgery for both
      lesions, with success. Intraoperatively, the aneurysm wall was found to be so
      thin and transparent that the inner blood turbulence could be seen, and it
      appeared highly susceptible to rupture. When a saccular, thin-walled AAA develops
      in association with AAC, early surgical intervention is mandatory regardless of
      the size of the aneurysm. (Ann Thorac Cardiovasc Surg 2003; 9: 326-9)

PMID- 14672532
TI  - Acute postoperative paraplegia complicating with emergency graft replacement of
      the ascending aorta for the type a dissection.
AB  - Postoperative paraplegia complicating with type A dissection is extremely rare.
      We describe a case of acute paraplegia after emergency graft replacement of the
      ascending aorta for type A dissection. A 63 year-old hypertensive man presented
      to hospital with chest pain. A chest computed tomography demonstrated an aortic
      dissection of the ascending aorta with mild pericardial effusion. Under deep
      hypothermic circulatory arrest with concomitant antegrade selective cerebral
      perfusion, the ascending aorta was replaced. The patient regained consciousness
      six hours after operation, however, he was complicated with paraplegia. All
      sensation was lost below the level of Th12. The cause of the paraplegia was
      assumed to be a thrombotic occlusion of costal arteries, which originated from
      the false lumen. Spinal fluid was drained for three days. Hyperbaric oxygenation
      therapy was started four days after onset of paraplegia. Fortunately, our patient
      recovered gradually, and he was doing well and was walking independently at one
      year follow-up. (Ann Thorac Cardiovasc Surg 2003; 9: 330-3)

PMID- 14672533
TI  - A successful management of concomitant renovascular hypertension and symptomatic
      subclavian steal syndrome due to Takayasu's arteritis using balloon angioplasty
      and axillo-axillary bypass grafting.
AB  - We present a case of Takayasu's arteritis with severe renovascular hypertension
      and symptomatic subclavian steal syndrome. A 60-year-old woman underwent
      successful percutaneous balloon renal angioplasty and axillo-axillary bypass
      grafting. The role of hybrid therapy, angioplasty and extra-anatomical bypass
      grafting for revascularization of symptomatic ischemia in this disease is
      reviewed. (Ann Thorac Cardiovasc Surg 2003: 9; 334-6)

PMID- 14672534
TI  - Internal iliac artery injury in a fractured pelvis.
AB  - This is a case of an 8 year-old boy who suffered a severe road traffic accident
      (RTA) with multiple fractures of the pelvis and right femur together with rupture
      of the urethra. After initial stabilization, he presented one month later with a
      large pseudoaneurysm of the left internal iliac artery. The patient underwent
      successful laparotomy, evacuation of the hematoma and ligation of the injured
      internal iliac artery. (Ann Thorac Cardiovasc Surg 2003; 9: 337-9)

PMID- 14672535
TI  - Secrets of insulin and IGF-1 regulation of insulin secretion revealed.
AB  - There has been ongoing controversy over the respective roles of insulin-like
      growth factor-1 receptors and insulin receptors in controlling insulin release
      from beta-cells of the pancreas. An acute knock-down experiment exploiting small
      interfering RNA approaches provides a resolution: both are required.

PMID- 14672536
TI  - Cardiac output by Portapres.
AB  - Portapres derives continuous estimates of cardiac output from the peripheral
      pulse and has the potential to be an extremely valuable physiological and
      clinical tool. We assessed Portapres estimates of cardiac output in healthy
      subjects at rest, during maximal treadmill exercise ( n = 8) and during decreases
      caused by orthostatic stress ( n = 8). Comparison with a rebreathing method
      indicated that Portapres tended to overestimate cardiac output. The random errors
      of the estimates (precision), expressed as +/- 2 S.D. of the differences between
      paired estimates during steady states, ranged between 1.2 and 2.6 litres/min. We
      conclude that these errors indicate that the method is probably only useful for
      assessing changes in individual subjects where large changes are anticipated, as
      during exercise. When smaller changes occur, as during orthostasis, the errors
      preclude the use of individual subject data and only permit group average data to
      be examined.

PMID- 14672537
TI  - Proximal C-terminal domain of sulphonylurea receptor 2A interacts with pore
      forming Kir6 subunits in KATP channels.
AB  - Functional KATP (ATP-sensitive potassium) channels are hetero-octamers of four
      Kir6 (inwardly rectifying potassium) channel subunits and four SUR (sulphonylurea
      receptor) subunits. Possible interactions between the C-terminal domain of SUR2A
      and Kir6.2 were investigated by co-immunoprecipitation of rat SUR2A C-terminal
      fragments with full-length Kir6.2 and by analysis of cloned KATP channel function
      and distribution in HEK-293 cells (human embryonic kidney 293 cells) in the
      presence of competing rSUR2A fragments. Three maltose-binding protein-SUR2A
      fusions, rSUR2A-CTA (rSUR2A residues 1254-1545), rSUR2A-CTB (residues 1254-1403)
      and rSUR2A-CTC (residues 1294-1403), were co-immunoprecipitated with full-length
      Kir6.2 using a polyclonal anti-Kir6.2 antiserum. A fourth C-terminal domain
      fragment, rSUR2A-CTD (residues 1358-1545) did not co-immunoprecipitate with
      Kir6.2 under the same conditions, indicating a direct interaction between Kir6.2
      and a 65-amino-acid section of the cytoplasmic C-terminal region of rSUR2A
      between residues 1294 and 1358. ATP- and glibenclamide-sensitive K+ currents were
      decreased in HEK-293 cells expressing full-length Kir6 and SUR2 subunits that
      were transiently transfected with fragments rSUR2A-CTA, rSUR2A-CTC and rSUR2A-CTE
      (residues 1294-1359) compared with fragment rSUR2A-CTD or mock-transfected cells,
      suggesting either channel inhibition or a reduction in the number of functional
      KATP channels at the cell surface. Anti-KATP channel subunit-associated
      fluorescence in the cell membrane was substantially lower and intracellular
      fluorescence increased in rSUR2A-CTE expressing cells; thus, SUR2A fragments
      containing residues 1294-1358 reduce current by decreasing the number of channel
      subunits in the cell membrane. These results identify a site in the C-terminal
      domain of rSUR2A, between residues 1294 and 1358, whose direct interaction with
      full-length Kir6.2 is crucial for the assembly of functional KATP channels.

PMID- 14672539
TI  - HIV infected adults do not have an excess of colonising bacteria in their large
      airways.
AB  - BACKGROUND: HIV infected adults have increased susceptibility to bacterial
      pneumonia but the underlying immune defect is poorly understood. We tested the
      hypothesis that HIV infection might be associated with increased bacterial
      colonisation of distal airways by nasal flora, which would then predispose
      patients to bacterial pneumonia. METHODS: Healthy volunteer adults with normal
      chest radiographs were recruited. Bronchoscopy was carried out and uncontaminated
      mucosal samples were collected from proximal and distal sites in the large
      airways using a protected specimen brush. Samples were cultured to detect typical
      respiratory tract colonising organisms, and the proportion of samples found to
      contain colonising bacteria compared between HIV infected and uninfected subjects
      using non-parametric tests. RESULTS: Forty-nine subjects were studied of whom 27
      were HIV infected. Colonising bacteria were identified in the nasopharynx of all
      subjects including Streptococcus pneumoniae in 6/49 subjects (5 HIV uninfected).
      Colonising bacteria were found in the distal airway of 6 subjects (3/27 HIV
      infected vs 3/22 HIV uninfected; chi2 = 0.07, p = 0.8). Streptococcus pneumoniae
      was identified in the trachea of all subjects with nasal colonisation but in the
      distal airway of only 1 subject. CONCLUSIONS: There was no evidence to support a
      hypothesis of increased airway bacterial colonisation in healthy HIV infected
      subjects.

PMID- 14672540
TI  - Methicillin-resistant Staphylococcus aureus (MRSA) in rehabilitation and chronic
      care-facilities: what is the best strategy?
AB  - BACKGROUND: The risk associated with methicillin-resistant Staphylococcus aureus
      (MRSA) has been decreasing for several years in intensive care departments, but
      is now increasing in rehabilitation and chronic-care-facilities (R-CCF). The aim
      of this study was to use published data and our own experience to discuss the
      roles of screening for MRSA carriers, the type of isolation to be implemented and
      the efficiency of chemical decolonization. DISCUSSION: Screening identifies over
      90% of patients colonised with MRSA upon admission to R-CCF versus only 50% for
      intensive care units. Only totally dependent patients acquire MRSA. Thus, strict
      geographical isolation, as opposed to "social reinsertion", is clearly of no
      value. However, this should not lead to the abandoning of isolation, which
      remains essential during the administration of care. The use of chemicals to
      decolonize the nose and healthy skin appeared to be of some value and the
      application of this procedure could make technical isolation unnecessary in a non
      negligible proportion of cases. SUMMARY: Given the increase in morbidity
      associated with MRSA observed in numerous hospitals, the emergence of a community
      acquired disease associated with these strains and the evolution of glycopeptide
      resistant strains, the voluntary application of a strategy combining screening,
      technical isolation and chemical decolonization in R-CCF appears to be an urgent
      matter of priority.

PMID- 14672538
TI  - Role of APC and DNA mismatch repair genes in the development of colorectal
      cancers.
AB  - Colorectal cancer is the third most common cause of cancer-related death in both
      men and women in the western hemisphere. According to the American Cancer
      Society, an estimated 105,500 new cases of colon cancer with 57,100 deaths will
      occur in the U.S. in 2003, accounting for about 10% of cancer deaths. Among the
      colon cancer patients, hereditary risk contributes approximately 20%. The main
      inherited colorectal cancers are the familial adenomatous polyposis (FAP) and the
      hereditary nonpolyposis colorectal cancers (HNPCC). The FAP and HNPCC are caused
      due to mutations in the adenomatous polyposis coli (APC) and DNA mismatch repair
      (MMR) genes. The focus of this review is to summarize the functions of APC and
      MMR gene products in the development of colorectal cancers.

PMID- 14672541
TI  - Lambda Red-mediated recombinogenic engineering of enterohemorrhagic and
      enteropathogenic E. coli.
AB  - BACKGROUND: The lambda Red recombineering technology has been used extensively in
      Escherichia coli and Salmonella typhimurium for easy PCR-mediated generation of
      deletion mutants, but less so in pathogenic species of E. coli such as EHEC and
      EPEC. Our early experiments with the use of lambda Red in EHEC and EPEC have led
      to sporadic results, leading to the present study to identify factors that might
      improve the efficiency of Red recombineering in these pathogenic strains of E.
      coli. RESULTS: In this report, we have identified conditions that optimize the
      use of lambda Red for recombineering in EHEC and EPEC. Using plasmids that
      contain a Ptac-red-gam operon and a temperature-sensitive origin of replication,
      we have generated multiple mutations (both marked and unmarked) in known
      virulence genes. In addition, we have easily deleted five O157-specific islands
      (O-islands) of EHEC suspected of containing virulence factors. We have examined
      the use of both PCR-generated substrates (40 bp of flanking homology) and plasmid
      derived substrates (approximately 1 kb of flanking homology); both work well and
      each have their own advantages. The establishment of the hyper-rec phenotype
      requires only a 20 minute IPTG induction period of red and gam. This
      recombinogenic window is important as constitutive expression of red and gam
      induces a 10-fold increase in spontaneous resistance to rifampicin. Other factors
      such as the orientation of the drug marker in recombination substrates and heat
      shock effects also play roles in the success of Red-mediated recombination in
      EHEC and EPEC. CONCLUSIONS: The lambda Red recombineering technology has been
      optimized for use in pathogenic species of E. coli, namely EHEC and EPEC. As
      demonstration of this technology, five O-islands of EHEC were easily and
      precisely deleted from the chromosome by electroporation with PCR-generated
      substrates containing drug markers flanked with 40 bp of target DNA. These
      results should encourage the use of lambda Red recombineering in these and other
      strains of pathogenic bacteria for faster identification of virulence factors and
      the speedy generation of bacterial mutants for vaccine development.

PMID- 14672542
TI  - The WD-repeat protein superfamily in Arabidopsis: conservation and divergence in
      structure and function.
AB  - BACKGROUND: The WD motif (also known as the Trp-Asp or WD40 motif) is found in a
      multitude of eukaryotic proteins involved in a variety of cellular processes.
      Where studied, repeated WD motifs act as a site for protein-protein interaction,
      and proteins containing WD repeats (WDRs) are known to serve as platforms for the
      assembly of protein complexes or mediators of transient interplay among other
      proteins. In the model plant Arabidopsis thaliana, members of this superfamily
      are increasingly being recognized as key regulators of plant-specific
      developmental events. RESULTS: We analyzed the predicted complement of WDR
      proteins from Arabidopsis, and compared this to those from budding yeast, fruit
      fly and human to illustrate both conservation and divergence in structure and
      function. This analysis identified 237 potential Arabidopsis proteins containing
      four or more recognizable copies of the motif. These were classified into 143
      distinct families, 49 of which contained more than one Arabidopsis member.
      Approximately 113 of these families or individual proteins showed clear homology
      with WDR proteins from the other eukaryotes analyzed. Where conservation was
      found, it often extended across all of these organisms, suggesting that many of
      these proteins are linked to basic cellular mechanisms. The functional
      characterization of conserved WDR proteins in Arabidopsis reveals that these
      proteins help adapt basic mechanisms for plant-specific processes. CONCLUSIONS:
      Our results show that most Arabidopsis WDR proteins are strongly conserved across
      eukaryotes, including those that have been found to play key roles in plant
      specific processes, with diversity in function conferred at least in part by
      divergence in upstream signaling pathways, downstream regulatory targets and /or
      structure outside of the WDR regions.

PMID- 14672543
TI  - Acclimatization to high altitude: truths and misconceptions.

PMID- 14672544
TI  - Report on the 13th International Hypoxia Symposium. Banff, Canada, February 19
      22, 2003.

PMID- 14672545
TI  - Going to high altitude with preexisting ocular conditions.
AB  - The goal of this paper is to review how preexisting ocular conditions may be
      affected by altitude exposure. Such preexisting conditions include dry eye
      problems, monocular visual loss, and potential problems following refractive
      surgery procedures, as well as the possible changes associated with some forms of
      retinal and optic nerve diseases. Although most such altitude-related visual
      difficulties are relatively minor, some have resulted in serious morbidity or
      even death at high altitude. This review will give the reader background
      regarding these potentially debilitating conditions in order to better prepare
      for exposure to high altitude environments.

PMID- 14672546
TI  - Persistence of the lactate paradox over 8 weeks at 3,800 m.
AB  - The arterial blood lactate [La] response to exercise increases in acute hypoxia,
      but returns to near the normoxic (sea level, SL) response after 2 to 5 weeks of
      altitude acclimatization. Recently, it has been suggested that this gradual
      return to the SL response in [La], known as the lactate paradox (LP),
      unexpectedly disappears after 8 to 9 weeks at altitude. We tested this idea by
      recording the [La] response to exercise every 2 weeks over 8 weeks at altitude.
      Five normal, fit SL-residents were studied at SL and 3,800 m (Pbar = 485 torr) in
      both normoxia (PIO2 = 150 torr) and hypoxia (PIO2 = 91 torr approximately air at
      3,800 m). Arterial [La] and blood gas values were determined at rest and during
      cycle exercise at the same absolute workloads (0, 25, 50, 75, 90, and 100% of
      initial SL-VO2Max) and exercise duration (4, 4, 4, 2, 1.5, and 0.75 min,
      respectively) at each time point. [La] curves were elevated in acute hypoxia at
      SL (p < 0.01) and at 3,800 m fell progressively toward the SL-normoxic curve (p <
      0.01). On the same days, [La] responses in acute normoxia showed essentially no
      changes over time and were similar to initial SL normoxic responses. We also
      measured arterial catecholamine levels at each load and found a close
      relationship to [La] over time, supporting a role for adrenergic influence on
      [La]. In summary, extending the time at this altitude to 8 weeks produced no
      evidence for reversal of the LP, consistent with prior data obtained over shorter
      periods of altitude residence.

PMID- 14672547
TI  - Cardiopulmonary function in high altitude residents of Ladakh.
AB  - We studied residents of high altitude in Ladakh, India, to determine the effects
      of altitude, age, gender, and ethnicity on gas exchange and pulmonary function.
      Physical examinations, including pulse oximetry, hemoglobin concentration, end
      tidal PCO2, and pulmonary function, were conducted on resting Ladakhi and Tibetan
      subjects at altitudes of 3300, 4200, and 4500 m. A total of 574 men and women,
      ranging in age from 17 to 82, were studied. At 3300 m, Ladakhis had higher heart
      rates than Tibetans in both genders and higher PETCO2 in women. Above 4000 m, 21
      of the 141 men studied (15%) had Hb concentrations higher than 20 g/dL, with one
      confirmed case of Monge's disease. There was no gender difference in SaO2 at any
      altitude except for pregnant women. At 4600 m, Tibetans had significantly higher
      peak flows and lower PETCO2 than Ladakhis. Ladakhi men had higher diastolic BP
      than women (91 vs. 81), with no difference in systolic BP. There was no gender
      difference in BP for Tibetans. An important spirometry finding for both groups
      was high air flows, with mid-maximal expiratory flow (MMEF) at 130% to 150% of
      predicted values, compared with 85% for sojourner controls, and FEV1/FVC at 115%,
      compared with sojourner controls at 98%. Improved lung mechanics may be an
      important adaptation to the lifelong sustained increase in resting ventilation as
      well as to indoor biomass smoke and outdoor dust exposure of these populations at
      high altitude.

PMID- 14672548
TI  - Effects of intermittent exposure to high altitude on pulmonary hemodynamics: a
      prospective study.
AB  - Chronic alveolar hypoxia due to disease or low atmospheric pressure at high
      altitude results in the development of hypoxic pulmonary hypertension. The
      effects of intermittent hypoxia on pulmonary hemodynamics in healthy men have not
      been studied. We aimed to investigate, prospectively, pulmonary hemodynamics in
      workers commuting between an elevation of 3700 and 4200 m (4-week working shift)
      and lowland, below 500 m (4 weeks of holiday). Pulmonary hemodynamics has been
      investigated by Doppler echocardiography in 26 healthy Caucasian males, mean age
      42 +/- 9 yr. First at lowland (760 m) and next during the fourth week of work at
      high altitude. Investigations were repeated in 21 subjects 1 year later at the
      end of the high-altitude exposure. The third series of investigations was
      performed 2 yr after the initial ones in 10 subjects who earlier had shown the
      strongest hypoxic vasoconstriction. At lowland, subjects presented with normal
      pulmonary hemodynamics. At high altitude, mean pulmonary artery pressure (PAPm)
      rose from 14.7 +/- 2.7 mmHg to 25.8 +/- 8.3 mmHg. One year later the PAPm
      remained unchanged in hypoxic conditions (25.0 +/- 7.3 mmHg). At the end of a 2
      year follow-up of 10 "hyperreactors," PAPm measured at the end of the hypoxic
      exposure was the same as at the initial investigation, averaging 28 +/- 4.0, 28
      +/- 3.5, and 29 +/- 2.5 mmHg at the beginning and at 1 and after 2 yr of
      intermittent exposure to high altitude. We concluded that intermittent exposure
      to 4000 m lasting 3 yr does not lead to development of permanent pulmonary
      hypertension.

PMID- 14672549
TI  - A pig model of high altitude pulmonary edema.
AB  - High altitude pulmonary edema (HAPE) affects unacclimatized individuals ascending
      rapidly to high altitude. The pathogenesis of HAPE is not fully elucidated, and
      many investigative techniques that could provide valuable information are not
      suitable for use in humans; thus, an animal model is desirable. Rabbits, sheep,
      dogs, and ferrets have been shown not to consistently develop HAPE, and studies
      in rats are limited by the animal's small size and inconsistent response. Pigs
      develop a marked pulmonary vasoconstrictive response to hypoxia, and preliminary
      studies of HAPE in pigs have been promising. To determine the suitability of pigs
      as an animal model of HAPE, we exposed six subadult (20 to 25 kg) pigs to
      normobaric hypoxia (10% oxygen) for 48 hr. One week before, and immediately after
      exposure to hypoxia, under anesthesia, arterial blood gases were obtained and
      bronchoalveolar lavage (BAL) and chest x-ray were performed. Hypoxia increased
      alveolar-arterial pressure difference for oxygen from 22 +/- 9 to 38 +/- 5 torr,
      p < 0.01) and red cell (from 12.3 +/- 5.9 to 27.4 +/- 5.3 cells x 10(5)/mL(-1), p
      < 0.001) and white cell (from 1.59 +/- 0.90 to 7.88 +/- 3.36 cells x 10(5)/mL(
      1), p < 0.05) concentrations in BAL in all animals. Total BAL protein
      concentration increased by 64% and fractional albumin by 38% (both p < 0.05)
      posthypoxia. One animal had evidence of pulmonary edema on X ray. Some pigs
      develop findings consistent with early HAPE when exposed to normobaric hypoxia.
      Increasing the duration of hypoxic exposure or exercising the animals in hypoxia
      may better model the disease process observed in humans with clinically
      significant HAPE.

PMID- 14672550
TI  - Beta-blockers may provoke oxygen desaturation during submaximal exercise at
      moderate altitudes in elderly persons.
AB  - Frequency of therapeutic beta-blocker use in elderly mountaineers is unknown.
      Therefore, the aim of this field study was to measure the regular beta-blocker
      intake in elderly persons visiting moderate altitudes. In a subset of
      mountaineers on beta-blockers, exercise response at two different altitude levels
      was compared to matched controls. The observed frequency of beta-blocked persons
      among the interviewed elderly mountaineers (age >35) was 7%, mainly (65%) due to
      hypertension. In subjects taking beta-blockers, arterial oxygen saturation (84 +/
      6% vs. 90 +/- 3%, p < 0.05) was decreased and heart rate (120 +/- 17 bpm vs. 112
      +/- 14 bpm, p = 0.01), rate pressure product (22,192 +/- 6459 vs. 17,576 +/-
      4010, p < 0.05), and ratings of perceived exertion (14 +/- 3 vs. 12 +/- 3, p <
      0.05) were increased during a submaximal step test at 2311 m compared to 1480 m.
      Mountaineers without beta-blocker intake showed no changes. Although the
      epidemiological data have to be interpreted with caution because of the small
      sample size and the limitation to a single geographical site, a large number of
      beta-blocked persons visiting high altitudes was observed. If confirmed in
      further studies, the increased heart work and exertion could indicate a reduced
      exercise tolerance of people taking beta-blockers during acute high altitude
      exposure.

PMID- 14672551
TI  - Medical considerations in the use of helicopters in mountain rescue.
AB  - The outcome of patient care can be dramatically improved by bringing rapid rescue
      and medical care to the mountain rescue scene and by rapid transport to a medical
      facility. The use of a helicopter for these purposes is common. It is necessary
      when it has clear advantages for victims in comparison with ground rescue and
      transport. Helicopters should work within the existing emergency medical system
      and must be staffed by appropriate mountain rescue and medically trained
      personnel. Activation time should be as short as possible. Activation of a
      helicopter for a mountain rescue should primarily include indication and
      assessment of flight and safety conditions. No other mediators or delaying
      factors should be permitted. The main safety criteria are appropriate mountain
      rescue and flight training, competence of air and ground crews, radio
      communication between the air and ground crews, and mission briefing before the
      rescue. Criteria for a helicopter used for mountain rescue are proper medical and
      rescue equipment, load capacity, adequate space, and others. There are two main
      groups of indications for use of a helicopter for mountain rescue: the patient's
      condition and the circumstances at the site of the accident. All persons
      responsible for the activation of the helicopter rescue operation should be aware
      of specific problems in the mountains or wilderness.

PMID- 14672552
TI  - Survival following severe acute hypoxia and cold.

PMID- 14672553
TI  - The r506 Q mutation of coagulation factor V gene in high altitude pulmonary-edema
      susceptible subjects.

PMID- 14672554
TI  - The enigmatic role of angiopoietin-1 in tumor angiogenesis.
AB  - A tumor vasculature is highly unstable and immature, characterized by a high
      proliferation rate of endothelial cells, hyper-permeability, and chaotic blood
      flow. The dysfunctional vasculature gives rise to continual plasma leakage and
      hypoxia in the tumor, resulting in constant on-sets of inflammation and
      angiogenesis. Tumors are thus likened to wounds that will not heal. The lack of
      functional mural cells, including pericytes and vascular smooth muscle cells, in
      tumor vascular structure contributes significantly to the abnormality of tumor
      vessels. Angiopoietin-1 (Ang1) is a physiological angiogenesis promoter during
      embryonic development. The function of Ang1 is essential to endothelial cell
      survival, vascular branching, and pericyte recruitment. However, an increasing
      amount of experimental data suggest that Ang1-stimulated association of mural
      cells with endothelial cells lead to stabilization of newly formed blood vessels.
      This in turn may limit the otherwise continuous angiogenesis in the tumor, and
      consequently give rise to inhibition of tumor growth. We discuss the enigmatic
      role of Ang1 in tumor angiogenesis in this review.

PMID- 14672555
TI  - Methylation profiling of twenty four genes and the concordant methylation
      behaviours of nineteen genes that may contribute to hepatocellular
      carcinogenesis.
AB  - To determine the possible role of the epigenetic mechanisms in carcinogenesis of
      the hepatocellular carcinoma, we methylation-profiled the promoter CpG islands of
      twenty four genes both in HCC tumors and the neighboring non-cancerous tissues of
      twenty eight patients using the methylation-specific PCR (MSP) method in
      conjunction with the DNA sequencing. In comparison with the normal liver tissues
      from the healthy donors, it was found that while remained unmethylated the ABL,
      CAV, EPO, GATA3, LKB1, NEP, NFL, NIS and p27KIP1 genes, varying extents of the
      HCC specific hypermethylation were found associated with the ABO, AR, CSPG2,
      cyclin a1, DBCCR1, GALR2, IRF7, MGMT, MT1A, MYOD1, OCT6, p57KIP2, p73, WT1 genes,
      and demethylation with the MAGEA1 gene, respectively. Judged by whether the
      hypermethylated occurred in HCC more frequently than in their neighboring normal
      tissues, the hypermethylation status of the AR, DBCCR1, IRF7, OCT6, and p73 genes
      was considered as the event specific to the late stage, while that the rest that
      lacked such a distinguished contrast, as the event specific to the early stage of
      HCC carcinogenesis. Among all the clinical pathological parameters tested for the
      association with, the hypermethylation of the cyclin a1 gene was more prevalent
      in the non-cirrhosis group (P=0.021) while the hypermethylated p16INK4a gene was
      more common in the cirrhosis group (P=0.017). The concordant methylation
      behaviors of nineteen genes, including the four previously studied and their
      association with cirrhosis has been evaluated by the best subgroup selection
      method. The data presented in this report would enable us to shape our
      understanding of the mechanisms for the HCC specific loss of the epigenetic
      stability of the genome, as well as the strategy of developing the novel robust
      methylation based diagnostic and prognostic tools.

PMID- 14672556
TI  - Tissue engineering of blood vessels with endothelial cells differentiated from
      mouse embryonic stem cells.
AB  - Endothelial cells (TEC3 cells) derived from mouse embryonic stem (ES) cells were
      used as seed cells to construct blood vessels. Tissue engineered blood vessels
      were made by seeding 8  106 smooth muscle cells (SMCs) obtained from rabbit
      arteries onto a sheet of nonwoven polyglycolic acid (PGA) fibers, which was used
      as a biodegradable polymer scaffold. After being cultured in DMEM medium for 7
      days in vitro, SMCs grew well on the PGA fibers, and the cell-PGA sheet was then
      wrapped around a silicon tube, and implanted subcutaneously into nude mice. After
      6~8 weeks, the silicon tube was replaced with another silicon tube in smaller
      diameter, and then the TEC3 cells (endothelial cells differentiated from mouse ES
      cells) were injected inside the engineered vessel tube as the test group. In the
      control group only culture medium was injected. Five days later, the engineered
      vessels were harvested for gross observation, histological and
      immunohistochemical analysis. The preliminary results demonstrated that the SMC
      PGA construct could form a tubular structure in 6~8 weeks and PGA fibers were
      completely degraded. Histological and immunohistochemical analysis of the newly
      formed tissue revealed a typical blood vessel structure, including a lining of
      endothelial cells (ECs) on the lumimal surface and the presence of SMC and
      collagen in the wall. No EC lining was found in the tubes of control group.
      Therefore, the ECs differentiated from mouse ES cells can serve as seed cells for
      endothelium lining in tissue engineered blood vessels.

PMID- 14672557
TI  - TGF-beta1-promoted epithelial-to-mesenchymal transformation and cell adhesion
      contribute to TGF-beta1-enhanced cell migration in SMMC-7721 cells.
AB  - Transforming growth factor-b1 (TGF-beta1), a multi-function polypeptide, is a
      double-edged sword in cancer. For some tumor cells, TGF-beta1 is a potent growth
      inhibitor and apoptosis inducer. More commonly, TGF-beta1 loses its growth
      inhibitory and apoptosis-inducing effects, but stimulates the metastatic capacity
      of tumor cells. It is currently little known about TGF-beta1-promoted cell
      migration in hepatocellular carcinoma (HCC) cells, let alone its mechanism. In
      this study, we found that TGF-beta1 lost its tumor-suppressive effects, but
      significantly stimulated cell migration in SMMC-7721 human HCC cells. By FACS and
      Western blot analysis, we observed that TGF-beta1 enhanced the expression of
      alpha5beta1 integrin obviously, and subsequently stimulated cell adhesion onto
      fibronectin (Fn). Furthermore, we observed that TGF-beta1 could also promote SMMC
      7721 cells adhesion onto laminin (Ln). Our data also provided evidences that TGF
      beta1 induced epithelial-to-mesenchymal transformation (EMT) in SMMC-7721 cells.
      First, SMMC-7721 cells clearly switched to the spindle shape morphology after TGF
      beta1 treatment. Furthermore, TGF-beta1 induced the down-regulation of E-cadherin
      and the nuclear translocation of beta-catenin. These results indicated that TGF
      beta1-promoted cell adhesion and TGF-beta1-induced epithelial-to-mesenchymal
      transformation might be both responsible for TGF-beta1-enhanced cell migration.

PMID- 14672558
TI  - The in vitro reconstitution of nucleosome and its binding patterns with HMG1/2
      and HMG14/17 proteins.
AB  - Using atomic force microscopy (AFM), the dynamic process of the in vitro
      nucleosome reconstitution followed by slow dilution from high salt to low salt
      was visualized. Data showed that the histone octamers were dissociated from DNA
      at 1M NaCl. When the salt concentration was slowly reduced to 650 mM and 300 mM,
      the core histones bound to the naked DNA gradually. Once the salt concentration
      was reduced to 50 mM the classic "beads-on-a-string" structure was clearly
      visualized. Furthermore, using the technique of the in vitro reconstitution of
      nucleosome, the mono- and di- nucleosomes were assembled in vitro with both
      HS2core (-10681 to -10970 bp) and NCR2 (-372 to -194 bp) DNA sequences in the 5
      flanking sequence of human b-globin gene. Data revealed that HMG 1/2 and HMG14/17
      proteins binding to both DNA sequences are changeable following the assembly and
      disassembly of nucleosomes. We suggest that the changeable binding patterns of
      HMG 14/17 and HMG1/2 proteins with these regulatory elements may be critical in
      the process of nucleosome assembly, recruitment of chromatin-modifying
      activities, and the regulation of human b-globin gene expression.

PMID- 14672559
TI  - Enhancement of germ cell apoptosis induced by ethanol in transgenic mice
      overexpressing Fas Ligand.
AB  - It was suggested that chronic ethanol exposure could result in testicular germ
      cell apoptosis, but the mechanism is still unclear. In the present study, we use
      a model of transgenic mice ubiquitously overexpressing human FasL to investigate
      whether Fas ligand plays a role in ethanol-induced testicular germ cell
      apoptosis. Both wild-type (WT) mice and transgenic (TG) mice were treated with
      acute ethanol (20% v/v) by introperitoneal injection for five times. After
      ethanol injection, WT mice displayed up-regulation of Fas ligand in the testes,
      which was shown by FITC-conjugated flow cytometry and western blotting. Moreover,
      TG mice exhibited significantly more apoptotic germ cells than WT mice did after
      ethanol injection, which was demonstrated by DNA fragmentation, PI staining flow
      cytometry and TUNEL staining. In addition, histopathological examination revealed
      that degenerative changes of epithelial component of the tubules occurred in FasL
      overexpressing transgenic mice while testicular morphology was normal in wild
      type mice after acute ethanol exposure, suggesting FasL expression determines the
      sensitivity of testes to ethanol in mice. In summary, we provide the direct
      evidences that Fas ligand mediates the apoptosis of testicular germ cells induced
      by acute ethanol using FasL transgenic mice.

PMID- 14672560
TI  - Purification and characterization of Moschatin, a novel type I ribosome
      inactivating protein from the mature seeds of pumpkin (Cucurbita moschata), and
      preparation of its immunotoxin against human melanoma cells.
AB  - A novel ribosome-inactivating protein designated Moschatin from the mature seeds
      of pumpkin (Cucurbita moschata) has been successively purified to homogeneity,
      using ammonium sulfate precipitation, CM-cellulose 52 column chromatography, Blue
      Sepharose CL-6B Affinity column chromatography and FPLC size-exclusion column
      chromatography. Moschatin is a type 1 RIP with a pI of 9.4 and molecular weight
      of approximately 29 kD. It is a rRNA N-glycosidase and potently blocked the
      protein synthesis in the rabbit reticulocyte lysate with a IC50 of 0.26 nM. Using
      the anti-human melanoma McAb Ng76, a novel immunotoxin Moschatin-Ng76 was
      prepared successfully and it efficiently inhibited the growth of targeted
      melanoma cells M21 with a IC50 of 0.04 nM, 1500 times lower than that of free
      Moschatin. The results implied that Moschatin could be used as a new potential
      anticancer agent.

PMID- 14672561
TI  - Effects of MEK inhibitor U0126 on meiotic progression in mouse oocytes:
      microtuble organization, asymmetric division and metaphase II arrest.
AB  - In this study we used U0126, a potent and specific inhibitor of MEK, to study the
      roles of MEK/ERK/p90rsk signaling pathway in the meiotic cell cycle of mouse
      oocytes. The phosphorylation of MAP kinase and p90rsk in the oocytes treated with
      1.5 microM U0126 was the same as that in oocytes cultured in drug-free medium.
      With 1.5 microM U0126 treatment, the spindles appeared normal as they formed in
      oocytes, but failed to maintain its structure. Instead, the spindle lost one pole
      or elongated extraordinarily. After further culture, some oocytes extruded
      gigantic polar bodies (>30 microm) that later divided into two small ones. Some
      oocytes underwent symmetric division and produced two equal-size daughter cells
      in which normal spindles formed. In oocytes with different division patterns, MAP
      kinase was normally phosphorylated. When the concentration of U0126 was increased
      to 15 mM, the phosphorylation of both MAPK and p90rsk were inhibited, while
      symmetric division was decreased. When incubating in medium containing 15 microM
      U0126 for 14 h, oocytes were activated, but part of them failed to emit polar
      bodies. MII oocytes were also activated by 15 microM U0126, at the same time the
      dephosphorylation of MAP kinase and p90rsk was observed. Our results indicate
      that 1) MEK plays important but not indispensable roles in microtubule
      organization; 2) MEK keeps normal meiotic spindle morphology, targets peripheral
      spindle positioning and regulates asymmetric division by activating some unknown
      substrates other than MAP kinase /p90rsk; and 3) activation of MEK/ERK/p90rsk
      cascade maintains MII arrest in mouse oocytes.

PMID- 14672562
TI  - Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac
      myocytes via regulating Bcl-2/Bax expression.
AB  - Intermittent hypoxia has been shown to provide myocardial protection against
      ishemia/reperfusion-induced injury. Cardiac myocyte loss through apoptosis has
      been reported in ischemia/reperfusion injury. Our aim was to investigate whether
      intermittent hypoxia could attenuate ischemia/reperfusion-induced apoptosis in
      cardiac myocytes and its potential mechanisms. Adult male Sprague-Dawley rats
      were exposed to hypoxia simulated 5000 m in a hypobaric chamber for 6 h/day,
      lasting 42 days. Normoxia group rats were kept under normoxic conditions.
      Isolated perfused hearts from both groups were subjected to 30 min of global
      ischemia followed by 60 min reperfusion. Incidence of apoptosis in cardiac
      myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP
      nick end labeling (TUNEL) and DNA agarose gel electrophoresis. Expressions of
      apoptosis related proteins, Bax and Bcl-2, in cytosolic and membrane fraction
      were detected by Western Blotting. After ischemia/reperfusion, enhanced recovery
      of cardiac function was observed in intermittent hypoxia hearts compared with
      normoxia group. Ischemia/reperfusion-induced apoptosis, as evidenced by TUNEL
      positive nuclei and DNA fragmentation, was significantly reduced in intermittent
      hypoxia group compared with normoxia group. After ischemia/reperfusion,
      expression of Bax in both cytosolic and membrane fractions was decreased in
      intermittent hypoxia hearts compared with normoxia group. Although
      ischemia/reperfusion did not induce changes in the level of Bcl-2 expression in
      cytosolic fraction between intermittent hypoxia and normoxia groups, the
      expression of Bcl-2 in membrane fraction was upregulated in intermittent hypoxia
      group compared with normoxia group. These results indicated that the
      cardioprotection of intermittent hypoxia against ischemia/reperfusion injury
      appears to be in part due to reduce myocardial apoptosis. Intermittent hypoxia
      attenuated ischemia/reperfusion-induced apoptosis via increasing the ratio of Bcl
      2/Bax, especially in membrane fraction.

PMID- 14672563
TI  - Flow-tissue interaction with compliance mismatch in a model stented artery.
AB  - The insertion of an endovascular prosthesis is known to have a thrombogenic
      effect that is also a consequence of the interaction between the flowing blood
      and the stented arterial segment; in fact the prosthesis induces a compliance
      mismatch and a possible small expansion along the vessel that eventually gives
      rise to an anomalous distribution of wall shear stresses. The fluid dynamics
      inside a rectilinear elastic vessel with compliance and section variation is
      studied here numerically. A recently introduced perturbative approach is employed
      to model the interaction between the fluid and the elastic tissue; this
      approximate technique is first validated by comparison with a complete solution
      within a simple one-dimensional model of the same system. Then it is applied to
      an axisymmetric model in order to evaluate the flow dynamics and the distribution
      of wall shear stress in the stented vessel. Compliance mismatch is shown to
      produce more intense negative wall shear stresses in the stented segment while
      rapid variations of wall shear stress are found at the stent ends. These effects
      are enhanced when the prosthesis is accompanied by a small increase of the vessel
      lumen.

PMID- 14672564
TI  - Modelling the fibrous tissue layer in cemented hip replacements: experimental and
      finite element methods.
AB  - The long-term fixation of cemented femoral components may be jeopardised by the
      presence of a fibrous tissue layer at the bone-cement interface. This study used
      both experimental and finite element (FE) methods to investigate the load
      transfer characteristics of two types of cemented hip replacements (Lubinus SPII
      and Muller-Curved) with a fibrous tissue layer. The experimental part
      investigated six stems of each type, where these were implanted in composite
      femurs with a specially selected silicone elastomer modelling the soft
      interfacial layer. Two fibrous tissue conditions were examined: a layer covering
      the full cement mantle, representing a revision condition; and a layer covering
      the proximal portion of the cement mantle, representing a non-revised implant
      with partial debonding and fibrous tissue formation. The FE method was used to
      model the full fibrous tissue layer condition, for both implants. The layer was
      modelled as a homogeneous, linearly isotropic material. A cross-comparison was
      performed of the experimental and FE findings. Agreement between experimental and
      FE models was verified to be within 15%. Varying the stiffness parameter of the
      FE soft tissue layer had little influence on the cortical bone strains, though
      had considerable effect on the cement strains. Stress shielding occurred for both
      stems under both fibrous tissue conditions, with the greatest reduction around
      the calcar. However, the cortical bone strains were generally larger than those
      for the equivalent well-fixed stems. The fibrous tissue layer was not found to
      increase the general strain pattern of the cement mantle, though localised
      regions of high stress were detected.

PMID- 14672565
TI  - Comparison of the elastic and yield properties of human femoral trabecular and
      cortical bone tissue.
AB  - The ability to determine trabecular bone tissue elastic and failure properties
      has biological and clinical importance. To date, trabecular tissue yield strains
      remain unknown due to experimental difficulties, and elastic moduli studies have
      reported controversial results. We hypothesized that the elastic and tensile and
      compressive yield properties of trabecular tissue are similar to those of
      cortical tissue. Effective tissue modulus and yield strains were calibrated for
      cadaveric human femoral neck specimens taken from 11 donors, using a combination
      of apparent-level mechanical testing and specimen-specific, high-resolution,
      nonlinear finite element modeling. The trabecular tissue properties were then
      compared to measured elastic modulus and tensile yield strain of human femoral
      diaphyseal cortical bone specimens obtained from a similar cohort of 34 donors.
      Cortical tissue properties were obtained by statistically eliminating the effects
      of vascular porosity. Results indicated that mean elastic modulus was 10% lower
      (p<0.05) for the trabecular tissue (18.0+/-2.8 GPa) than for the cortical tissue
      (19.9+/-1.8 GPa), and the 0.2% offset tensile yield strain was 15% lower for the
      trabecular tissue (0.62+/-0.04% vs. 0.73+/-0.05%, p<0.001). The tensile
      compressive yield strength asymmetry for the trabecular tissue, 0.62 on average,
      was similar to values reported in the literature for cortical bone. We conclude
      that while the elastic modulus and yield strains for trabecular tissue are just
      slightly lower than those of cortical tissue, because of the cumulative effect of
      these differences, tissue strength is about 25% greater for cortical bone.

PMID- 14672566
TI  - Oscillometric assessment of airway obstruction in a mechanical model of vocal
      cord dysfunction.
AB  - Vocal cord dysfunction (VCD) is characterized by inappropriate adduction of the
      vocal cords, particularly during inspiration, resulting in obstruction and
      airflow limitation. Direct visualization of the vocal cords with laryngoscopy is
      the 'gold standard' for diagnosing VCD. However, it is an invasive technique that
      may induce airway irritation. The aim of this study was to determine whether the
      forced oscillation technique (FOT) is useful to estimate the degree of closure of
      a non-linear orifice under conditions mimicking those found in VCD. The FOT (5
      Hz, +/-1 cm H(2)O) was applied to an airway model simultaneously with constant
      levels of flow in the normal breathing range (0-0.8l/s). Pressure-flow (P(0)
      V'(0)) curves, quasi-static resistance (R(eff)) and oscillatory resistance
      (R(FOT)) were measured in orifices with different areas (0.15-1.12 cm2) and
      shapes and in an orifice with variable area. Their pressure-flow relationship
      followed a quadratic model. Changes in R(FOT) normalized by flow
      (DeltaR(FOT)/V'(0)) were related to changes in the area of the vocal cord model
      (1/A(VC2)(2)-1/A(VC1)(2)) from maximum aperture (A(VC1)) to different degrees of
      closure (A(VC2)): DeltaR(FOT)/V'(0)=1.93(1/A(VC2)(2)-1/A(VC1)(2))+2.08 cm
      H(2)Os(2)/l(2); r(2)=0.99. We conclude that FOT could be a useful tool for non
      invasively assessing glottic closure in VCD diagnosis, obviating the need for
      other invasive techniques.

PMID- 14672567
TI  - Contact stresses and fatigue life in a knee prosthesis: comparison between in
      vitro measurements and computational simulations.
AB  - The evaluation of contact areas and pressures in total knee prosthesis is a key
      issue to prevent early failure. The first part of this study is based on the
      hypothesis that the patterns of contact stresses on the tibial insert of a knee
      prosthesis at different stages of the gait cycle could be an indicator of the
      wear performances of a knee prosthesis. Contact stresses were calculated for a
      mobile bearing knee prosthesis by means of finite element method (FEM). Contact
      areas and stresses were also measured through in vitro tests using Fuji Prescale
      film in order to support the FEM findings. The second part of this study
      addresses the long-term structural integrity of metal tibial components in terms
      of fatigue life by means of experimental tests and FEM simulations. Fatigue
      experimental evaluations were performed on Cr-Co alloy tibial tray, based on ISO
      standards. FEM models were used to calculate the stress patterns. The failure
      risk was estimated with a standard fatigue criterion on the basis of the results
      obtained from the FEM calculations. Experimental and computational results showed
      a positive matching.

PMID- 14672568
TI  - Time-lapsed microstructural imaging of bone failure behavior.
AB  - Many bones within the axial and appendicular skeleton are subjected to repetitive
      loading during the course of ordinary daily activities. If this loading is of
      sufficient magnitude or duration, failure of the bone tissue may result. Until
      recently the structural analysis of these fractures has been limited to two
      dimensional sections. Due to the inherent destructiveness of this method, dynamic
      assessment of fracture progression has not been possible. An image-guided
      technique to analyze structural failure has been developed utilizing step-wise
      micro-compression in combination with time-lapsed micro-computed tomographic
      imaging. This technique allows, for the first time, direct three-dimensional
      visualization and quantification of fracture initiation and progression on the
      microscopic level and relates the global failure properties of trabecular bone to
      those of the individual trabeculae. The goals of this project were first to
      design and fabricate a novel micro-mechanical testing system, composed of a micro
      compression device and a material testing and data acquisition system; and
      second, to validate the testing system to perform step-wise testing of trabecular
      bone specimens based on image-guided failure analysis. Due to the rate dependant
      properties of bone, stress relaxation was a concerning factor with respect to the
      step-wise testing method. In order to address these concerns, the results of the
      step-wise testing method were compared to those obtained from a conventional
      continuous test (considered to be the gold standard for the step-wise compressive
      mechanical testing) over the same total strain range and testing conditions. This
      was performed using porous aluminum alloy samples with highly reproducible and
      homogenous structural properties as well as trabecular bone samples from a single
      whale vertebra. Five cylinders from aluminum foam and trabecular whale bone each
      were compressed and imaged in a step-wise fashion from 0% to 20% strain at
      intervals of 2%, 4%, 8%, 12%, 16% and 20%. Mechanical properties obtained from
      the continuous and step-wise methods were not significantly different for both
      aluminum foam and whale bone specimens (p>0.05). Both testing methods yielded
      very similar stress-strain graphs with almost identical elastic and plastic
      regions with overlaying standard error bars for both whale bone and aluminum foam
      specimens. This was further concurred by performing regression analyses between
      the stress data from both testing methods (r(2)=0.98 for whale bone and aluminum
      foam specimens). Animations of fracture initiation and progression revealed that
      failure always occurred in local bands with the remaining regions of the
      structure largely unaffected independent of structure type. In conclusion, we
      found step-wise micro-compression to be a valid approach for image-guided failure
      assessment (IGFA) with high precision and accuracy as compared to classical
      continuous testing. We expect findings from upcoming studies of IGFA of human
      vertebral bone to improve our understanding of the relative importance of
      densitometric, morphological, and loading factors in the etiology of spontaneous
      fractures of the spine. Eventually, this improved understanding may lead to more
      successful approaches to the prevention of age-related fatigue fractures.

PMID- 14672569
TI  - Micro-mechanical sensing platform for the characterization of the elastic
      properties of the ovum via uniaxial measurement.
AB  - Stiffness is an important parameter in determining the physical properties of
      living tissue. Recently, considerable biomedical attention has centered on the
      mechanical properties of living tissues at the single cell level. In the present
      paper, the Young's modulus of zona pellucida of bovine ovum was calculated using
      Micro Tactile Sensor (MTS) fabricated using piezoelectric (PZT) material. The
      sensor consists of a needle-shaped 20-microm transduction point made using a
      micro-electrode puller and mounted on a micro-manipulator platform. Measurements
      were made under microscopic control, using a suction pipette to support the ovum
      in the same horizontal axis as the MTS. Young's modulus of ovum was found to be
      25.3+/-7.94 kPa (n=28). This value was indirectly determined based on calibration
      curves relating change in resonance frequency (Deltaf(0)) of the sensor with tip
      displacement for gelatin at concentrations of 4%, 6%, and 8%. The regression
      equation between the rate of change in resonance frequency (versus sensor tip
      displacement), Deltaf(0)/x and Young's modulus is Deltaf(0)/x (Hz/microm)=0.2992
      x Young's modulus (kPa)-1.0363. It is concluded that a reason that the stiffness
      of ovum measured in the present study is approximately six times larger than
      previously reported, may be due to the absence of large deformation present in of
      existing methodologies.

PMID- 14672570
TI  - Development of biomechanical response corridors of the thorax to blunt ballistic
      impacts.
AB  - Human responses are critical to understanding injury biomechanics in blunt
      ballistic impacts, which are defined as 20-200 g projectiles impacting at 20-250
      m/s. 13 human cadavers were exposed to three distinct ballistic impacts of the
      chest to determine force-time, deflection-time and force-deflection responses.
      Comparisons were made between biomechanical responses for ballistic impacts and
      those previously reported for lower speed, higher mass impacts. Impact condition
      B (140 g at 40 m/s) gave the largest peak force 10,602+/-2226 N and deflection
      54.7+/-14.6 mm. Impact condition A (140 g at 20 m/s) involved lower impact energy
      and produced lower peak force 3383+/-761 N and deflection 25.9+/-3.1 mm, as did
      impact condition C (40 g at 60 m/s), which gave 3158+/-309 N and 20.1+/-7.8 mm.
      The results indicate each impact condition gives distinctive responses, which
      differ from those previously reported in the automotive literature for lower
      speed impacts. This information provides the foundation for future biomechanical
      research in the area of blunt ballistic impacts, specifically the development of
      test surrogates and evaluation of protective equipment.

PMID- 14672571
TI  - A phenomenological model for estimating metabolic energy consumption in muscle
      contraction.
AB  - A phenomenological model for muscle energy consumption was developed and used in
      conjunction with a simple Hill-type model for muscle contraction. The model was
      used to address two questions. First, can an empirical model of muscle energetics
      accurately represent the total energetic behavior of frog muscle in isometric,
      isotonic, and isokinetic contractions? And second, how does such a model perform
      in a large-scale, multiple-muscle model of human walking? Four simulations were
      conducted with frog sartorius muscle under full excitation: an isometric
      contraction, a set of isotonic contractions with the muscle shortening a constant
      distance under various applied loads, a set of isotonic contractions with the
      muscle shortening over various distances under a constant load, and an isokinetic
      contraction in lengthening. The model calculations were evaluated against results
      of similar thermal in vitro experiments performed on frog sartorius muscle. The
      energetics model was then incorporated into a large-scale, multiple-muscle model
      of the human body for the purpose of predicting energy consumption during normal
      walking. The total energy estimated by the model accurately reflected the
      observed experimental behavior of frog muscle for an isometric contraction. The
      model also accurately reproduced the experimental behavior of frog muscle heat
      production under isotonic shortening and isokinetic lengthening conditions. The
      estimated rate of metabolic energy consumption for walking was 29% higher than
      the value typically obtained from gait measurements.

PMID- 14672572
TI  - Flow patterns in an endovascular stent-graft for abdominal aortic aneurysm
      repair.
AB  - Endovascular exclusion of the abdominal aortic aneurysm (AAA) has been carried
      out in selected patients during the past decade. The deployment of a complex
      multicomponent endovascular device in an aneurysmal aorta may alter the local
      haemodynamics and lead to thrombosis and intimal hyperplasia development. The aim
      of this in vitro study was to investigate the flow patterns using flow
      visualisation and laser Doppler anemometry in a commercial bifurcated stent
      graft. Two configurations of the stent-graft, endo-stent and exo-stent, were
      investigated in an idealised planar AAA model. The flow structures in the main
      trunk in both configurations of the stent-graft are three-dimensional with
      complex secondary structures. However, these flow structures were not entirely
      caused by the stent-graft. The stent struts in the endo-stent configuration cause
      localised alteration in the flow pattern but the overall flow structures were not
      significantly affected. Low velocity regions in the main trunk and flow
      separation in the stump region and the curved segment of the iliac limbs were
      observed. These areas are associated with thrombosis in the clinical situation.
      Improvements in the design of endovascular devices may remove these areas of
      unfavourable flow patterns and lead to better clinical performance.

PMID- 14672573
TI  - Muscle force is determined also by muscle relative position: isolated effects.
AB  - Effects on force of changes of the position of extensor digitorum longus muscle
      (EDL) relative to surrounding tissues were investigated in rat. Connective tissue
      at the muscle bellies of tibialis anterior (TA), extensor hallucis longus (EHL)
      and EDL was left intact, to allow myofascial force transmission. The position of
      EDL muscle was altered, without changing EDL muscle-tendon complex length, and
      force exerted at proximal and distal tendons of EDL as well as summed force
      exerted at the distal tendons of TA and EHL muscles (TA+EHL) were measured.
      Proximal and distal EDL forces as well as distal TA+EHL force changed
      significantly on repositioning EDL muscle. These muscle position-force
      characteristics were assessed at two EDL lengths and two TA+EHL lengths. It was
      shown that changes of muscle force with length changes of a muscle is the result
      of the length changes per se, as well as of changes of relative position of parts
      of the muscle. It is concluded that in addition to length, muscle position
      relative to its surroundings co-determines isometric muscle force.

PMID- 14672574
TI  - Tensile and compressive behaviour of the bovine periodontal ligament.
AB  - The mechanical response of the bovine periodontal ligament (PDL) subjected to
      uniaxial tension and compression is reported. Several sections normal to the
      longitudinal axis of bovine incisors and molars were extracted from different
      depths. Specimens with dimensions 10 x 5 x 2 mm including dentine, PDL and
      alveolar bone were obtained from these sections. Scanning electron microscopy
      suggested a strong similarity between the bovine PDL and the human PDL
      microstructure described in the literature. The prepared specimens were tested in
      a custom made uniaxial testing machine. They were clamped on their bone and
      dentine extremities and immersed in a saline solution at 37 degrees C. Stress
      strain curves indicated that the PDL is characterized by a non-linear and time
      dependent mechanical behaviour with the typical features of collagenous soft
      tissues. The curves exhibited hysteresis and preconditioning effects. The
      mechanical parameters evaluated in tension were maximum tangent modulus,
      strength, maximizer strain and strain energy density. For the molars, all these
      parameters increased with depth except for the apical region. For the incisors,
      all parameters increased with depth except ultimate strain which decreased. It
      was assumed that collagen fibre density and orientation were responsible for
      these findings.

PMID- 14672575
TI  - Estimation of gait cycle characteristics by trunk accelerometry.
AB  - This study reports on the novel use of a portable system to measure gait cycle
      parameters. Measurements were made by a triaxial accelerometer over the lower
      trunk during timed walking over a range of self-administered speeds. Signals from
      each trial were transformed to a horizontal-vertical coordinate system and
      analyzed by an unbiased autocorrelation procedure to obtain cadence, step length,
      and measures of gait regularity and symmetry. By curvilinear interpolation, speed
      dependent gait parameters could be compared at a normalized speed. It was
      demonstrated that analysis of gait cycle parameters which previously required
      fixed laboratory equipment and paced walking procedures, now can be made from
      data obtained by a timing device and a portable sensor at free walking speeds.

PMID- 14672576
TI  - Design and numerical implementation of a 3-D non-linear viscoelastic constitutive
      model for brain tissue during impact.
AB  - Finite Element (FE) head models are often used to understand mechanical response
      of the head and its contents during impact loading in the head. Current FE models
      do not account for non-linear viscoelastic material behavior of brain tissue. We
      developed a new non-linear viscoelastic material model for brain tissue and
      implemented it in an explicit FE code. To obtain sufficient numerical accuracy
      for modeling the nearly incompressible brain tissue, deviatoric and volumetric
      stress contributions are separated. Deviatoric stress is modeled in a non-linear
      viscoelastic differential form. Volumetric behavior is assumed linearly elastic.
      Linear viscoelastic material parameters were derived from published data on
      oscillatory experiments, and from ultrasonic experiments. Additionally, non
      linear parameters were derived from stress relaxation (SR) experiments at shear
      strains up to 20%. The model was tested by simulating the transient phase in the
      SR experiments not used in parameter determination (strains up to 20%, strain
      rates up to 8s(-1)). Both time- and strain-dependent behavior were predicted
      accurately (R2>0.96) for strain and strain rates applied. However, the stress was
      overestimated systematically by approximately 31% independent of strain(rate)
      applied. This is probably caused by limitations of the experimental data at hand.

PMID- 14672577
TI  - In vivo tendon force measurement of 2-week duration in sheep.
AB  - Tendon tension in vivo may be determined indirectly by measuring intratendinous
      pressure, by using a buckle transducer or by measuring the tendon strain. All of
      these methods require appropriate calibration, which is highly dependent on
      various variables. To measure the tendon load in vivo during a period of 2 weeks
      in sheep, a measurement technique has been developed using a force sensor
      interposed serially between the humeral head and the tendon end. Within a
      supporting frame, a flexion-sensitive force transducer is subjected to three
      point bending stress. The load is transmitted by sutures from the tendon end
      through a hole in the sensor frame, orthogonal to the force transducer. In this
      configuration, the sensor measures the tensile force acting on the tendon,
      largely independent of the loading direction. The sensor was screwed to the
      humeral head and connected to the tendon end which was previously released from
      its insertion site along with a bone chip, using sutures. Connecting wires passed
      subcutaneously to a skin outlet about 30 cm away from the transducer. The sensor
      output was linear to the measured load up to 300 N, with maximum hysteresis of
      18% full scale. All sensors worked in vivo without drift over a period of up to
      14 days with no change in the calibration data. Forces up to 310 N have been
      recorded in vivo with daily tension measurements. This study shows that serial
      tendon tension measurement is feasible and allows for reliable, repeatable
      recording of the absolute tendon tension at the expense of tendon integrity.

PMID- 14672578
TI  - A simple method for measurement of maximal downstroke power on friction-loaded
      cycle ergometer.
AB  - The aim of this study was to propose and validate a post-hoc correction method to
      obtain maximal power values taking into account inertia of the flywheel during
      sprints on friction-loaded cycle ergometers. This correction method was obtained
      from a basic postulate of linear deceleration-time evolution during the initial
      phase (until maximal power) of a sprint and included simple parameters as
      flywheel inertia, maximal velocity, time to reach maximal velocity and friction
      force. The validity of this model was tested by comparing measured and calculated
      maximal power values for 19 sprint bouts performed by five subjects against 0.6-1
      N kg(-1) friction loads. Non-significant differences between measured and
      calculated maximal power (1151+/-169 vs. 1148+/-170 W) and a mean error index of
      1.31+/-1.20% (ranging from 0.09% to 4.20%) showed the validity of this method.
      Furthermore, the differences between measured maximal power and power neglecting
      inertia (20.4+/-7.6%, ranging from 9.5% to 33.2%) emphasized the usefulness of
      power correcting in studies about anaerobic power which do not include inertia,
      and also the interest of this simple post-hoc method.

PMID- 14672579
TI  - Analysis of effects of friction on the deformation behavior of soft tissues in
      unconfined compression tests.
AB  - Frictionless specimen/platen contact in unconfined compression tests has
      traditionally been assumed in determining material properties of soft tissues via
      an analytical solution. In the present study, the suitability of this assumption
      was examined using a finite element method. The effect of the specimen/platen
      friction on the mechanical characteristics of soft tissues in unconfined
      compression was analyzed based on the published experimental data of three
      different materials (pigskin, pig brain, and human calcaneal fat). The soft
      tissues were considered to be nonlinear and viscoelastic; the friction
      coefficient at the contact interface between the specimens and platens was
      assumed to vary from 0.0 to 0.5. Our numerical simulations show that the tissue
      specimens are, due to the specimen/platen friction, not compressed in a uniform
      stress/strain state, as has been traditionally assumed in analytical analysis.
      The stress of the specimens obtained with the specimen/platen friction can be
      greater than those with the frictionless specimen/platen contact by more than
      50%, even in well-controlled test conditions.

PMID- 14672580
TI  - The effect of step-wise increased stretching on rat calvarial osteoblast collagen
      production.
AB  - Mechanical forces regulate the function of bone cells. In this paper, the effects
      of cyclic stretching on osteoblasts derived from rat calvaria were studied at a
      magnitude occurring in physiological loaded bone tissue. A four-point bending
      apparatus was used to apply cyclic stretching on osteoblasts. Stretching at 500
      microepsilon for 2-24 h resulted in an increase in matrix synthesis(P<0.01). In
      contrast, the cyclic stretching at 1000 and 1500 microepsilon for 2-24 h
      inhibited osteoblast collagen production (P<0.01). We also described our new
      loading method to increase strain magnitude step-by-step. The strain magnitude
      increased by 500 microepsilon increments from 500 to 1500 microepsilon every 2 or
      12 h, respectively. Results showed that osteoblasts could absorb large amount of
      proline for collagen synthesis when stretched at 500 microepsilon. However, not
      all the absorbed proline was used to synthesize collagen. Some of it was stored
      in cells. When the suitable signal (500 microepsilon) was changed to an
      inhibiting signal (1000 microepsilon), cells responded to it accordingly and
      released proline to medium. These results demonstrate that the response of
      osteoblasts is dependent on the magnitude of the strain applied and cells can
      adjust their bio-chemical response to adapt to the changing environmental
      stimulation.

PMID- 14672581
TI  - Assessment of screw displacement axis accuracy and repeatability for joint
      kinematic description using an electromagnetic tracking device.
AB  - Screw displacement axes (SDAs) have been employed to describe joint kinematics in
      biomechanical studies. Previous reports have investigated the accuracy of SDAs
      combining various motion analysis techniques and smoothing procedures. To our
      knowledge, no study has assessed SDA accuracy describing the relative movement
      between adjacent bodies with an electromagnetic tracking system. This is
      important, since in relative motion, neither body is fixed and consequently
      sensitivity to potential measurement errors from both bodies may be significant.
      Therefore, this study assessed the accuracy of SDAs for describing relative
      motion between two moving bodies. We analyzed numerical simulated data, and
      physical experimental data recorded using a precision jig and electromagnetic
      tracking device. The numerical simulations demonstrated SDA position accuracy
      (p=0.04) was superior for single compared to relative body motion, whereas
      orientation accuracy (p=0.2) was similar. Experimental data showed data-filtering
      (Butterworth filter) improved SDA position and orientation accuracies for
      rotation magnitudes smaller or equal to 5.0 degrees, with no effect at larger
      rotation magnitudes (p<0.05). This suggests that in absence of a filter, SDAs
      should only be calculated at rotations of greater than 5.0 degrees. For rotation
      magnitudes of 0.5 degrees (5.0 degrees ) about the SDA, SDA position and
      orientation error measurements determined from filtered experimental data were
      3.75+/-0.30 mm (3.31+/-0.21 mm), and 1.10+/-0.04 degrees (1.04+/-0.03 degrees ),
      respectively. Experimental accuracy values describing the translation along and
      rotation about the SDA, were 0.06+/-0.00 mm and 0.09+/-0.01 degrees,
      respectively. These small errors establish the capability of SDAs to detect small
      translations, and rotations. In conclusion, application of SDAs should be a
      useful tool for describing relative motion in joint kinematic studies.

PMID- 14672583
TI  - Introduction to: heresy and orthodoxy in medical theory and research.

PMID- 14672584
TI  - The role of methods in maintaining orthodox beliefs in health research.
AB  - Views about correct ways of obtaining knowledge develop from socially constructed
      tenets and beliefs. The dominant beliefs about how health research should be
      conducted are derived from the biomedical model of human health. The beliefs are
      maintained by traditions developed in support of the orthodox model and by power
      relationships. This paper examines the impact of the orthodox views of the
      biomedical model on the research methods used to investigate population health
      issues. Experimental design is the "gold standard" for research in the biomedical
      model. Beliefs about the superiority of experimental research have affected most
      types of health research. The role that methods assume in maintaining the
      orthodoxy is examined. Acceptance in other health disciplines of the attitudes of
      the dominant paradigm and limited options for research and training in
      alternatives to the orthodoxy became major influences reinforcing orthodox
      beliefs about health research.

PMID- 14672585
TI  - The ambivalence of error: "scientific ideology" in the history of the life
      sciences and psychosomatic medicine.
AB  - This paper discusses the concept of "scientific ideology" as it appears in the
      work of the historian and philosopher of medicine Georges Canguilhem, whose work
      is becoming increasingly well known and used amongst anglophone social
      scientists. Whilst addressing the problematic of legitimacy and illegitimacy in
      the history of science, the concept of "scientific ideology" does something
      different and more complex than either the opposition between science and false
      science, or the one between orthodoxy and heresy, allow for. On the one hand, it
      enables us to preserve a crucial acknowledgment of the specificity of science in
      general, and of medical science in particular. On the other hand, it also allows
      us to challenge the sharp contrast between science and non-science by setting
      that contrast in a diachronic perspective. Drawing also on the work of Isabelle
      Stengers, the last part of the paper discusses an application of the concept of
      scientific ideology in relation to the field of psychosomatic medicine and
      psychoneuroimmunology.

PMID- 14672586
TI  - From the biomedical model to the Islamic alternative: a brief overview of medical
      practices in the contemporary Arab world.
AB  - Following its climax in the 8th century under the Abbasids of Baghdad, the Arab
      world entered a prolonged period of division and decadence. "Western" medicine
      was introduced in the 19th century with the support of the general population.
      The historical participation of Arabs in the elaboration of that "Western"
      biomedical model and its apparently consensual re-introduction into the Arab
      world diffused any sense of cognitive alienation vis-a-vis practices promoted
      initially by non-Arab doctors. In the late 1960s, Islamist thinkers started
      proposing "Islamic medicine" as an alternative to the encroachment of the
      "Western" biomedical model within Arab and Muslim nations. In Islamic medicine,
      disease is attributed to lack of attention to the spiritual dimension of human
      beings, yet intermediate causal pathways are not provided. Alongside "orthodox"
      concepts, Islamic medicine promotes some herbal remedies, in addition to faith
      healing through prayer and the recitation of holy verses. While most of those
      practices may be beneficial, they may cause some harm to patients if they entail
      delaying or denying timely recourse to "orthodox" medical care. There are
      currently no Islamic medicine training programs in any Arab country, and Islamic
      medicine has not emerged as a comprehensive health alternative comparable to
      other non-Western health models.

PMID- 14672587
TI  - Schism and heresy in the development of orthodox medicine: the threat to medical
      hegemony.
AB  - Medical and scientific knowledge is not intrinsically different from other kinds
      of knowledge and has gone through the same processes in terms of its development.
      As a profession, medicine achieved its dominance in the 19th century and has
      subsequently consolidated its power base. A socio-historical perspective shows us
      that medicine has no more and no less fraud, heresy, schism, and relative
      knowledge than any other equivalent forms of knowledge. Orthodox medicine emerged
      from a number of healing systems in the 19th century by claiming the superiority
      and consequent authority of the biomedical model and its special relationship to
      laboratory science. This process has been seen by some to resemble the growth of
      religious orthodoxy and the emergence of alternative beliefs with the dissenting
      medical systems, based on different paradigms, becoming analogous to religious
      sects. An increasing body of opinion rejects the notion of "objective" knowledge
      and sees medical knowledge and practice as "socially constructed". An examination
      of HIV/AIDS measurement and 19th century craniology and contagion and anti
      contagion theories indicates processes which are "contextual" rather than
      "objective". Heresy and schism are natural concomitants of socially constructed
      knowledge, functioning as providers of impetus and change and, as such, are to be
      welcomed as non-orthodox challenges.

PMID- 14672588
TI  - Dissent and heresy in medicine: models, methods, and strategies.
AB  - Understanding the dynamics of dissent and heresy in medicine can be aided by the
      use of suitable frameworks. The dynamics of the search for truth vary
      considerably depending on whether the search is competitive or cooperative and on
      whether truth is assumed to be unitary or plural. Insights about dissent and
      heresy in medicine can be gained by making comparisons to politics and religion.
      To explain adherence to either orthodoxy or a challenging view, partisans use a
      standard set of explanations; social scientists use these plus others, especially
      symmetrical analyses. There is a wide array of methods by which orthodoxy
      maintains its domination and marginalises challengers. Finally, challengers can
      adopt various strategies in order to gain a hearing.

PMID- 14672589
TI  - Clinical medicine and the quest for certainty.
AB  - Orthodox medicine works in a scientific framework which often discounts knowledge
      arising outside biomedical models and the statistical means by which these are
      tested. Alternative medicine cannot meet these standards because it is holistic
      and individual in its orientations toward the understanding and treatment of
      human illness. But in fact the dominant model also has problems with surgery and
      other areas such as family practice as sub-disciplines where individualised
      caring solutions are important. These prominently include areas in which wider
      social and economic concerns directly impinge on health care so that we need a
      more liberal attitude to medical knowledge and discovery. I suggest that this
      wider conception is more in keeping with the Hippocratic ethos as a whole and
      with the idea of a healing praxis. Because our aim as doctors and health care
      professionals is to help people, and our knowledge is directed towards furthering
      this end, medicine is a practical science not able to stand apart and build
      theories in detached contemplation from within the ivory tower of the academy.
      However the practicality of medicine and the assurance needed to poison people or
      inflict grievous bodily harm in an effort to help them often puts a premium on
      certainties in our thinking about clinical medicine before the scientific basis
      for such certainty has been established. Therefore, hand in hand with the
      professional calling that is health care, goes the need for a certain style of
      belief in what one is doing and its ultimate rightness. This leads to an almost
      unique profile for medicine among the sciences.

PMID- 14672590
TI  - Negative pathways to psychiatric care and ethnicity: the bridge between social
      science and psychiatry.
AB  - It has been consistently reported that the African-Caribbean population in the UK
      are more likely than their White counterparts to access psychiatric services via
      the police and under compulsion. The reasons for these differences are poorly
      understood. This paper comprises two main parts. The first provides a
      comprehensive review of research in this area, arguing the current lack of
      understanding stems from a number of methodological limitations that characterise
      the research to date. The issue of ethnic variations in pathways to psychiatric
      care has been studied almost exclusively within a medical epidemiological
      framework, and the potential insights offered by sociological and anthropological
      research in the fields of illness behaviour and health service use have been
      ignored. This has important implications as the failure of research to move
      beyond enumerating differences in sources of referral to psychiatric services and
      rates of compulsory admission means no recommendations for policy or service
      reform have been developed from the research. The second part of the paper sets
      out the foundations for future research, arguing that the pathway to care has to
      be studied as a social process subject to a wide range of influences, including
      the cultural context within which illness is experienced. It is further argued
      that Kleinman's (Patients and healers in the context of culture: an exploration
      of the borderland between anthropology, medicine and psychiatry, University of
      California Press, Los Angeles, 1980) Health Care System model offers a
      particularly valuable preliminary framework for organising and interpreting
      future research. It is only through gaining a more qualitative understanding of
      the processes at work in shaping different responses to mental illness and
      interactions with mental health services that the patterns observed in
      quantitative studies can be fully understood. This further reflects the need for
      a bridge between the social sciences and psychiatry if services are to be
      developed to respond to the increasing diversity of modern societies.

PMID- 14672591
TI  - Reforming health care financing in Bulgaria: the population perspective.
AB  - Health financing reform in Bulgaria has been characterised by lack of political
      consensus on reform direction, economic shocks, and, since 1998, steps towards
      social insurance. As in other eastern European countries, the reform has been
      driven by an imperative to embrace new ideas modelled on systems elsewhere, but
      with little attention to whether these reflect popular values. This study
      explores underlying values, such as views on the role of the state and
      solidarity, attitudes to, and understanding of compulsory and voluntary
      insurance, and co-payments. The study identifies general principles (equity,
      transparency) considered important by the population and practical aspects of
      implementation of reform. Data were obtained from a representative survey
      (n=1547) and from 58 in-depth interviews and 6 focus groups with users and health
      professionals, conducted in 1997 before the actual reform of the health financing
      system in Bulgaria. A majority supports significant state involvement in health
      care financing, ranging from providing safety net for the poor, through co
      subsidising or regulating the social insurance system, to providing state
      financed universal free care (half of all respondents). Collectivist values in
      Bulgaria remain strong, with support for free access to services regardless of
      income, age, or health status and progressive funding. There is strong support
      (especially among the well off) for a social insurance system based on the
      principle of solidarity and accountability rather than the former tax-based
      model. The preferred health insurance fund was autonomous, state regulated,
      financing only health care, and offering optional membership. Voluntary insurance
      and, less so, co-payments were acceptable if limited to selected services and
      better off groups. In conclusion, a health financing system under public control
      that fits well with values and population preferences is likely to improve
      compliance and be more sustainable. Universal health insurance appears to attract
      most support, but a broader public debate involving less empowered people is
      needed to resolve misunderstandings and create realistic expectations.

PMID- 14672592
TI  - Exploring the pathways leading from disadvantage to end-stage renal disease for
      indigenous Australians.
AB  - Indigenous Australians are disadvantaged, relative to other Australians, over a
      range of socio-economic and health measures. The age- and sex-adjusted incidence
      of end-stage renal disease (ESRD)--the irreversible preterminal phase of chronic
      renal failure--is almost nine times higher amongst Indigenous than it is amongst
      non-indigenous Australians. A striking gradient exists from urban to remote
      regions, where the standardised ESRD incidence is from 20 to more than 30 times
      the national incidence. We discuss the profound impact of renal disease on
      Indigenous Australians and their communities. We explore the linkages between
      disadvantage, often accompanied by geographic isolation, and both the initiation
      of renal disease, and its progression to ESRD. Purported explanations for the
      excess burden of renal disease in indigenous populations can be categorised as:
      primary renal disease explanations;genetic explanations;early development
      explanations; and socio-economic explanations. We discuss the strengths and
      weaknesses of these explanations and suggest a new hypothesis which integrates
      the existing evidence. We use this hypothesis to illuminate the pathways between
      disadvantage and the human biological processes which culminate in ESRD, and to
      propose prevention strategies across the life-course of Indigenous Australians to
      reduce their ESRD risk. Our hypothesis is likely to be relevant to an
      understanding of patterns of renal disease in other high-risk populations,
      particularly indigenous people in the developed world and people in developing
      countries. Furthermore, analogous pathways might be relevant to other chronic
      diseases, such as diabetes and cardiovascular disease. If we are able to confirm
      the various pathways from disadvantage to human biology, we will be better placed
      to advocate evidence-based interventions, both within and beyond the scope of the
      health-care system, to address the excess burden of renal and other chronic
      diseases among affected populations.

PMID- 14672593
TI  - Coercive sex in rural Uganda: prevalence and associated risk factors.
AB  - Despite growing recognition of the problem, relatively little is known about the
      issue of coercive sex in developing countries. This study presents findings from
      a community-based survey of 4279 reproductive-aged women in current partnerships
      in the Rakai District of Uganda carried out in 1998-99. One in four women in our
      study report having experienced coercive sex with their current male partner,
      with most women reporting its occasional occurrence. In a regression analysis of
      risk factors for coercive sex, conventional socio-demographic characteristics
      emerged as largely unpredictive of the risk of coercive sex. Behavioral risk
      factors-most notably, younger age of women at first intercourse and alcohol
      consumption before sex by the male partner-were strongly and positively related
      to the risk of coercive sex. Coercive sex was also strongly related to
      perceptions of the male partner's HIV risk, with women who perceived their
      partner to be at highest risk experiencing almost three times the risk of
      coercive sex relative to low risk partnerships. Supplemental analysis of 1-year
      longitudinal data provides additional support for the hypothesis that coercive
      sex may frequently be a consequence of women's perceptions of increased HIV risk
      for their male partner. The findings of this study are discussed in terms of the
      need for sexual violence prevention programs more generally in settings such as
      Uganda, and in terms of the possible importance of incorporating issues of sexual
      and physical violence within current HIV prevention programs.

PMID- 14672594
TI  - Comparing directly measured standard gamble scores to HUI2 and HUI3 utility
      scores: group- and individual-level comparisons.
AB  - Directly measured standard gamble (SG) utility scores reflect the respondent's
      assessment and valuation of their own health status. Scores from the health
      utilities index (HUI) are based on self-assessed health status but valued using
      community preferences obtained using the SG. Our objectives were to find if mean
      directly measured utility scores agree with mean HUI mark 2 (HUI2) and mean HUI
      mark 3 (HUI3) scores. Also, if individual directly measured utility scores agree
      with HUI2 and HUI3 scores, and whether HUI2 and HUI3 scores agree. Questionnaires
      based on the HUI2 and HUI3 health-status classification systems were administered
      by interviewers to 140 teenage survivors of extremely low birthweight (ELBW) and
      124 control group teens. Respondents were asked to think about their own usual
      health states using six dimensions from HUI2 and value that state using the SG.
      Mean SG scores are compared with mean HUI2 and mean HUI3 scores using paired
      sample t-tests. Mean HUI2 scores are compared with mean HUI3 scores. Agreement
      among scores is assessed using intra-class correlation coefficient (ICC). The
      effect of severity of health-state morbidity on agreement was assessed using
      three approaches. ELBW cohort mean (standard deviation) SG, HUI2, and HUI3 scores
      were 0.90 (0.20), 0.89 (0.14), and 0.80 (0.22). Results for controls were 0.93
      (0.11), 0.95 (0.09), and 0.89 (0.13). Mean SG and HUI2 scores did not differ;
      mean SG and HUI3 did differ; mean HUI2 and HUI3 also differed. At the individual
      level for ELBW, the ICCs between SG and HUI2, SG and HUI3, and HUI2 and HUI3
      scores were 0.13, 0.28, and 0.64. For controls the ICCs were 0.14, 0.24, and
      0.56. HUI2 scores appear to match directly measured utility scores reasonably
      well at the group level. HUI2 and HUI3 scores differ systematically. At the
      individual level, however, HUI2 and HUI3 scores are poor substitutes for directly
      measured scores.

PMID- 14672595
TI  - Lay conceptions of the ethical and scientific justifications for random
      allocation in clinical trials.
AB  - Randomised controlled trials (RCTs) play a central role in modern medical
      advance, and they require participants who understand and accept the procedures
      involved. Published evidence suggests that RCT participants often fail to
      understand that treatments are allocated at random and that clinicians are in
      equipoise about which treatment is best. We examine background assumptions that
      members of the public might draw upon if invited to take part in a RCT. Four
      studies (N=82; 67; 67; 128), in the UK, identified whether members of the public
      (i). accept that an individual clinician might be genuinely unsure which of two
      treatments was better; (ii). judge that when there is uncertainty it is
      acceptable to suggest deciding at random; (iii). recognise scientific benefits of
      random allocation to treatment conditions in a trial. Around half the
      participants were loathe to accept that a clinician could be completely
      uncertain, and this was no different whether the context was one of individual
      treatment or research. Most participants found it unacceptable to suggest
      allocating treatment at random, though there was weak evidence that a research
      context may reduce the unacceptability. Participants did not judge that more
      certain knowledge would be gained about which treatment was best when treatments
      were allocated at random rather than by patient/doctor choice: scientific
      benefits of randomisation were apparently not recognised. Judgements were no
      different in non-medical contexts. Results suggest a large mismatch between the
      assumptions underlying the trial design, and the assumptions that lay
      participants can bring to bear when they try to make sense of descriptive
      information about randomisation and equipoise. Previous attempts to improve
      understanding by improving the clarity or salience of trial information, or of
      making explicit the research context, while helpful, may need to be supplemented
      with accessible explanations for random allocation.

PMID- 14672596
TI  - Governing peanuts: the regulation of the social bodies of children and the risks
      of food allergies.
AB  - This paper explores the way in which children with life-threatening food
      allergies, their parents and their public caregivers have increasingly been made
      subject to both projects of moral regulation and mechanism of governance aimed at
      the management of risk. We argue that new regulatory measures in Canada designed
      to significantly change the food consumption practices among children in
      elementary schools have three main consequences. First, they structure the
      relationship between ideologies of individualism and community so as to blur the
      distinction between the public and private dimensions of school life. Second,
      such efforts ensure that a discourse, formerly concerned with the problem of
      health promotion, has been supplanted by new sets of discourses styled by absent
      experts that focus on the management of risk. Third, such regulatory practices
      have a particular dual effect that is characteristic of liberal welfare
      governance. On the one hand, they encourage the individualized development of
      self-governing subjects, and on the other, they stimulate a heightened moral
      problematization of 'safe' eating habits within the environment of the elementary
      school.

PMID- 14672597
TI  - Dilemmas in sharing care: maternal provision of professionally driven therapy for
      children with disabilities.
AB  - This paper explores some of the dilemmas that result when mothers and
      professionals collaborate in providing care to young children with disabilities
      within a US public program called Early Intervention. Successful collaboration
      between professionals and activist parents resulted in the program having a
      "family centered" approach, but the implementation of that approach is
      problematic. Professionals transmit therapeutic knowledge and skills to mothers
      of young children with special needs, urging them to perform therapeutic care
      work with their children. Through these efforts, professionals create a
      "therapeutic imperative" for mothers, expecting them to do therapeutic work that
      usually exceeds the amount of work that professionals do with their children.
      This paper explores the dilemmas mothers and professionals face when implementing
      family centered care and the ways in which mothers and professionals negotiate
      contested understandings of the optimal mixture of public (professional) and
      private (maternal) provision of therapeutic care to young children with
      disabilities.

PMID- 14672598
TI  - From compliance to concordance: barriers to accomplishing a re-framed model of
      health care interactions.
AB  - As a framework for organising health care interactions, compliance and adherence
      have come in for increasing criticism in recent years. It has been suggested that
      interactions with patients should not be viewed simply as opportunities to
      reinforce instructions around treatment: rather, they should be seen as a space
      where the expertise of patients and health professionals can be pooled to arrive
      at mutually agreed goals. This concept-known as concordance-is attracting
      increasing interest in health services research within the UK. In this paper, we
      seek to empirically explore the relevance of a re-framed consultation through
      qualitative interviews with a small group of English speaking patients of
      Pakistani origin with a diagnosis of type 2 diabetes. We suggest that the focus
      of many respondents in this study on material and structural factors limiting
      diabetic regimen integration and the emphasis on a 'doctor-centred' model of
      health care interactions represent distinct problems for the accomplishment of
      the concordance project. However, given that some patients sought greater
      understanding and appreciation by health professionals of the subjective aspects
      of living with diabetes, if it is evaluated at the level of health care
      relationships, rather than health outcomes (such as improved compliance)
      concordance may well be a significant development for those who suggest that
      respect for the patients agenda is a fundamental aspect of health care.

PMID- 14672599
TI  - Maternal literacy and health behavior: a Nepalese case study.
AB  - This article addresses the question of whether literacy could be mediating the
      relationships of schooling to maternal health behavior in populations undergoing
      demographic transition. Recent studies in which literacy was directly assessed
      suggest a literacy pathway to demographic change. The literacy skills of 167
      urban and rural mothers of school-aged children in Lalitpur District of the
      Kathmandu Valley of Nepal were assessed by tests of reading comprehension,
      academic language proficiency, health media skills and health narrative skill, as
      part of studies in the urban and rural communities that included a maternal
      interview and ethnographic fieldwork on the contexts of family life, health care
      and female schooling. Regression analysis of the data indicates the retention of
      literacy skills in adulthood and their influence on health behavior; ethnographic
      evidence shows that selective bias in school attainment does not account for the
      results. Further direct assessment studies are recommended.

PMID- 14672607
TI  - De novo autoimmune hepatitis after liver transplantation.

PMID- 14672608
TI  - Studies on the mechanism of accumulation of cholesterol in the gallbladder
      mucosa. Evidence that sterol 27-hydroxylase is not a pathogenetic factor.
AB  - BACKGROUND/AIMS: Cholesterolosis is characterized by accumulation of esterified
      cholesterol in human gallbladder mucosa. The present study aimed at investigating
      possible pathogenetic factors for cholesterolosis. The hypothesis was tested that
      a reduced sterol 27-hydroxylase or an increased amount of ACAT-1 enzyme may be of
      importance. METHODS: Gall bladder mucosa and bile were obtained from patients
      with cholesterol gallstones undergoing cholecystectomy (30 with and 43 without
      cholesterolosis). RESULTS: In cholesterolosis, the gall bladder mucosa was
      characterized by a several-fold increase in esterified cholesterol and normal
      content of free cholesterol. The amount of ACAT-1 protein, measured by
      immunoblotting, was similar in patients with and without cholesterolosis. The
      level of 27-hydroxycholesterol in gallbladder mucosa was elevated sevenfold as
      compared with cholesterol in patients with cholesterolosis. Most (87%) of this
      oxysterol was esterified and the accumulation is most probably secondary to the
      higher total amount of cholesterol in the cells. Patients with cholesterolosis
      had normal levels of both sterol 27-hydroxylase mRNA (real time polymerase chain
      reaction) and protein (immunoblotting). The enzymatic activity of the sterol 27
      hydroxylase in gallbladder mucosa was normal or increased in cholesterolosis.
      CONCLUSIONS: The pathogenesis of cholesterolosis may be multifactorial, but is
      not caused by reduced efflux of cholesterol due to a defect sterol 27-hydroxylase
      mechanism.

PMID- 14672609
TI  - Transcriptional reprogramming in murine liver defines the physiologic
      consequences of biliary obstruction.
AB  - BACKGROUND/AIMS: While the metabolic and histological responses to cholestasis
      are recognized, the consequences of impaired biliary flow on liver gene
      expression are largely undefined. We hypothesized that biliary obstruction
      results in transcriptional reprogramming that dictates the physiologic response.
      METHODS: We determined global gene expression in murine livers 1-21 days
      following bile duct ligation. Total hepatic cRNA from experimental and sham mice
      was hybridized to Affymetrix gene chips. Gene expression data was analyzed by
      GeneSpring software and validated by Northern analysis. RESULTS: We found 92
      genes over-expressed > or =2-fold at one or more time points following bile duct
      ligation. Functional classification of these genes revealed the activation of
      three main biological processes in a sequential and time-restricted fashion. At
      day 1, genes involved in sterol metabolism were uniquely over-expressed,
      including HMG-CoA reductase, the rate-limiting enzyme of cholesterol
      biosynthesis. This was followed by an increased expression of growth-promoting
      genes at day 7, the time point coinciding with peak cholangiocyte proliferation.
      In later phases (days 14-21), the liver over-expressed genes encoding structural
      proteins and proteases. CONCLUSIONS: Transcriptional reprogramming in the liver
      following biliary obstruction favors the activation of genes regulating
      metabolism, cell proliferation, and matrix remodeling in a time-restricted and
      sequential fashion.

PMID- 14672610
TI  - A progressive familial intrahepatic cholestasis type 2 mutation causes an
      unstable, temperature-sensitive bile salt export pump.
AB  - BACKGROUND/AIMS: Progressive familial intrahepatic cholestasis type 2 (PFIC-2)
      patients have a defect in the hepatocanalicular bile salt secretion. The disease
      is caused by mutations in the bile salt export pump (BSEP). Ten different
      missense mutations have been described. In this study, we analysed the effect of
      the D482G PFIC-2 mutation on BSEP function. METHODS: Adenosine triphosphatase
      (ATPase) and taurocholate transport assays were performed with full-length mouse
      Bsep (mBsep) with and without the D482G mutation. The effect on expression and
      subcellular sorting was studied in HepG2 cells, stably expressing enhanced green
      fluorescent protein (EGFP)-tagged mBsep proteins. RESULTS: The D482G mutation did
      not significantly affect the taurocholate transport activity of mBsep, even
      though the bile salt-inducible ATPase activity of the mutant protein was slightly
      reduced. Protein expression and canalicular sorting were strongly affected by the
      D482G mutation. Mutant EGFP-mBsep protein was only partly glycosylated and
      detected in both the canalicular membrane and the cytoplasm. At 30 degrees C, the
      mutant mRNA and protein levels were strongly increased, and the protein was
      predominantly glycosylated and efficiently targeted to the canalicular membrane.
      CONCLUSIONS: These data suggest that PFIC-2 patients with the D482G mutation
      express a functional, but highly unstable, temperature-sensitive bile salt export
      pump.

PMID- 14672611
TI  - Microbial mimics are major targets of crossreactivity with human pyruvate
      dehydrogenase in primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: Previous studies on patients with primary biliary cirrhosis
      (PBC) have shown extensive cross-reactivity between the dominant B- and T-cell
      epitopes of human pyruvate dehydrogenase complex-E2 (PDC-E2), and microbial
      mimics. Such observations have suggested microbial infection as having a role in
      the induction of anti-mitochondrial antibodies, through a mechanism of molecular
      mimicry. However the biological significance of these cross-reactivities is
      questionable, because PDC-E2 is so highly conserved among various species.
      METHODS: Interrogating protein databases, ten non-PDC-E2 microbial sequences with
      high degree of similarity to PDC-E2(212-226) were found in Escherichia coli (6),
      Helicobacter pylori, Pseudomonas aeruginosa, Cytomegalovirus, and Haemophilus
      influenzae. We report on a study testing reactivity and competitive cross
      reactivity against these respective peptides, and in some cases the parent
      protein, using sera from 55 patients with PBC, compared to reactivity of 190
      pathological and 28 healthy controls. RESULTS: Cross-reactivity to E. coli mimics
      was commonly seen in PBC, and in a subset of pathological controls except where
      there was no evidence of urinary tract infection and correlated with anti
      mitochondrial reactivity. CONCLUSIONS: E. coli/PDC-E2 cross-reactive immunity
      characterizes primary biliary cirrhosis; the large number of E. coli immunogenic
      mimics may account for the dominance of the major PDC-E2 autoepitope.

PMID- 14672612
TI  - A randomized placebo controlled trial of vitamin E for alcoholic hepatitis.
AB  - BACKGROUND/AIMS: The effect of vitamin E administration on clinical and
      laboratory parameters of liver function and on markers of fibrogenesis was
      assessed in patients with mild to moderate alcoholic hepatitis in a double blind
      placebo controlled randomized trial. METHODS: Twenty-five patients received 1000
      I.U. of vitamin E per day, while 26 patients received placebo for 3 months. The
      patients were followed for 1 year after entry into the trial. RESULTS: Vitamin E
      did not result in significant greater decreases in serum aminotransferases and
      serum bilirubin or in greater increases in serum albumin as compared with
      placebo. Prothrombin time did not change, while serum creatinine remained in the
      normal range. Monocyte nuclear nuclear factor-kappa B binding activity decreased
      in patients who remained abstinent, regardless of whether they received vitamin
      E. As regards markers of hepatic fibrogenesis, vitamin E treatment decreased
      serum hyaluronic acid (P<0.05) while serum aminoterminal peptide of type III
      procollagen did not change in either group. Four patients in the treatment group
      and five in the placebo group died during the 1-year study. CONCLUSIONS: Vitamin
      E treatment improves serum hyaluronic acid but has no beneficial effects on tests
      of liver function in patients with mild to moderate alcoholic hepatitis.

PMID- 14672613
TI  - The methionine-choline deficient dietary model of steatohepatitis does not
      exhibit insulin resistance.
AB  - BACKGROUND/AIMS: Non-alcoholic steatohepatitis is an important disease whose
      pathophysiology remains incompletely understood, although in humans a strong
      association with insulin resistance exists. Mice fed a methionine-choline
      deficient (MCD) diet develop steatohepatitis, however the influence of insulin in
      this model is unknown. METHODS: Male FVB/NJ mice were fed the MCD, MCD control or
      chow diet for 10 or 28 days. Fasting glucose, ALT, triglyceride and insulin was
      measured. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were
      performed followed by quantitative insulin sensitivity check index (QUICKI)
      determination. RESULTS: ALT levels were significantly higher in the MCD group.
      Fasting glucose was 81+/-5 mg/dl in MCD diet fed mice, compared to MCD controls
      (196+/-46 mg/dl) and chow (199+/-15 mg/dl) (P<0.0001). During GTT and ITT, the
      effect of glucose administration on blood glucose was dampened, and the insulin
      effect more pronounced in the MCD group (P=0.026 and P<0.001). QUICKI in MCD fed
      mice was significantly higher than in the chow fed mice. CONCLUSIONS: GTT, ITT
      and QUICKI confirmed the absence of insulin resistance in the MCD fed mice. This
      model causes fibrosing steatohepatitis and may help delineate the non-insulin
      resistant mechanisms involved in human steatohepatitis.

PMID- 14672614
TI  - Green tea polyphenol epigallocatechin-3-gallate inhibits platelet-derived growth
      factor-induced proliferation of human hepatic stellate cell line LI90.
AB  - BACKGROUND/AIMS: Green-tea polyphenols are known to have anti-fibrotic properties
      of the skin and the artery. The proliferation of hepatic stellate cells (HSC) is
      closely related to the progression of liver fibrosis in chronic liver diseases.
      We investigated the inhibitory effect of epigallocatechin-3-gallate (EGCG), the
      major potential inhibitory component of green-tea polyphenols, on the
      proliferation of HSC. The aim of this study was to clarify the molecular
      mechanisms of EGCG inhibition of HSC proliferation. METHODS: A cultured human
      hepatic stellate cell line LI90 was used for this study. The cells were
      stimulated by platelet-derived growth factor (PDGF)-BB in the presence or absence
      of EGCG. Proliferation was determined by bromodeoxy-uridine incorporation. The
      mRNA expressions of collagen alpha1(I) and (IV) were evaluated by a quantitative
      reverse transcription-polymerase chain reaction. PDGF receptor tyrosine
      phosphorylation was detected using anti-phosphotyrosine antibody. PDGF receptor
      radioligand binding assay was performed by [125I]-PDGF-BB. RESULTS: EGCG
      inhibited the PDGF-BB-induced cell-proliferation and collagen alpha1(I) and (IV)
      mRNA expressions. EGCG reduced the autophosphorylation of the PDGF receptor. EGCG
      blocked PDGF-BB binding to its receptor in a non-competitive manner. CONCLUSIONS:
      EGCG has an inhibitory effect on PDGF-induced proliferation of HSC, and the
      blocking of PDGF-BB binding to its receptor may be the mechanism behind this
      effect.

PMID- 14672615
TI  - 4-Hydroxynonenal as a selective pro-fibrogenic stimulus for activated human
      hepatic stellate cells.
AB  - BACKGROUND/AIMS: 4-Hydroxynonenal (HNE) is a putative pro-fibrogenic product of
      oxidative stress able to elicit apoptosis and cytotoxicity in several cell types.
      This study has been performed to evaluate its 'in vivo' levels in injured liver
      and whether HNE may induce apoptosis and/or affect selected phenotypic responses
      in activated human hepatic stellate cells (HSC/MF). METHODS/RESULTS: During the
      development of acute liver injury induced by CCl(4), liver tissue HNE levels were
      in the range 0.5-10 microM, as shown by high performance liquid chromatography
      analysis. Cultured human HSC/MF, developed cytotoxicity only if exposed to very
      high HNE concentrations (25-50 microM) without any sign of induction of classic,
      caspase-dependent apoptosis, as assessed by evaluating morphology and biochemical
      parameters of cell death. HNE, at non-cytotoxic doses, up-regulated procollagen
      type I and tissue inhibitor of metalloproteinases-1 gene expression and/or
      protein synthesis without significantly affecting chemotaxis (wound healing and
      haptotaxis assay), matrix metalloproteinases 1 and 2 mRNA expression and activity
      as well as basal DNA synthesis. CONCLUSIONS: HNE, at concentrations compatible
      with those detected in vivo, does not elicit HSC/MF classic apoptosis but,
      rather, may act as a potent pro-fibrogenic stimulus for the expression of genes
      involved in excess extracellular matrix deposition and proposed as survival
      signals for HSC/MF.

PMID- 14672616
TI  - Corticosteroids stimulate selectively transforming growth factor (TGF)-beta
      receptor type III expression in transdifferentiating hepatic stellate cells.
AB  - BACKGROUND/AIMS: Transforming growth factor (TGF)-beta receptors mediate TGF-beta
      signaling in activated hepatic stellate cells (HSC). This leads to pleiotropic
      cellular effects, e.g. to the production of extracellular matrix which is a
      hallmark for the development of liver fibrosis. Glucocorticoids and their
      receptors interact with the TGF-beta signaling pathway on the transcriptional and
      translational level. METHODS: To characterize TGF-beta receptor expression during
      HSC transdifferentiation and to study the influence of corticosteroids on
      receptor transcription in several liver cells, we established a real-time
      polymerase chain reaction procedure for mRNA quantification with gene-specific
      standards. RESULTS: All three TGF-beta receptor mRNAs are present in HSC and
      myofibroblasts. Whereas TGF beta receptor type I (T beta RI) shows a comparable
      mRNA expression during HSC transdifferentiation, T beta RII and T beta RIII mRNA
      concentration decreases in the course of time. In comparison with activated HSC T
      beta RIII mRNA is very low expressed in freshly isolated Kupffer cells and
      hepatocytes. Eight hours after corticosteroid treatment T beta RIII mRNA
      increased significantly in a time-and dose-dependent manner while the mRNA
      expression of T beta RI and T beta RII is not altered. The degree of induction of
      T beta RIII mRNA levels is also dependent upon the nature of the stimulating
      hormone: dexamethasone, hydrocortisone and aldosterone show different effects.
      CONCLUSIONS: The increase of T beta RIII by corticosteroids indicates that these
      hormones are important regulators of this receptor and thereby they can modulate
      TGF-beta signaling.

PMID- 14672617
TI  - Proapoptotic effect of hepatitis C virus CORE protein in transiently transfected
      cells is enhanced by nuclear localization and is dependent on PKR activation.
AB  - BACKGROUND/AIMS: HCV-CORE protein has been implicated in the regulation of
      apoptosis of infected cells acting as full-length or C-terminus deleted forms and
      resulting in both proapoptotic and antiapoptotic effects in different
      experimental conditions. METHODS: We have fused full-length and C-terminus
      deleted CORE with GFP to assess intracellular localization in transiently
      transfected cell lines and primary hepatocytes. Apoptosis of cells expressing
      different levels of chimeric proteins was quantified by cytometry. RESULTS: Full
      length CORE localized mainly in the cytoplasm, but nuclear staining was also
      observed, being more evident in primary human hepatocytes. Nuclear staining only
      was observed in cells expressing truncated CORE. Full-length CORE induced
      apoptosis in approximately 15-20% of transfected cells with low expression and in
      approximately 40-50% of those with high expression of viral protein.
      Interestingly, 40-50% of cells transfected with truncated CORE underwent
      apoptosis, independently of protein expression levels. CORE-induced apoptosis was
      significantly reduced in the presence of a protein kinase R (PKR) inhibiting
      peptide and truncated CORE was able to enhance translocation of PKR into nucleoli
      where CORE/PKR colocalization was observed. CONCLUSIONS: These results suggest
      that nuclear forms of HCV-CORE are generated in vivo in primary hepatocytes and
      induce PKR-dependent apoptosis, a mechanism that might have a relevant role
      during natural infection.

PMID- 14672618
TI  - Melatonin inhibits nuclear factor kappa B activation and oxidative stress and
      protects against thioacetamide induced liver damage in rats.
AB  - BACKGROUND/AIMS: Free radical-mediated oxidative stress has been implicated in
      the pathogenesis of acute liver injury. The aim of our study was to investigate
      whether melatonin, a potent free radical scavenger could prevent fulminant
      hepatic failure in rats. METHODS: Liver damage was induced by two consecutive
      injections of thioacetamide (TAA, 300 mg/kg/i.p.) at 24 h intervals. Treatment
      with melatonin (3 mg/kg/daily, i.p) was initiated 24 h prior to TAA. RESULTS:
      Twenty-four h after the second TAA injection, serum liver enzymes and blood
      ammonia were lower in rats treated with TAA+melatonin compared to TAA (P<0.001).
      Liver histology was significantly improved and the mortality in the melatonin
      treated rats was decreased (P<0.001). The increased nuclear binding of nuclear
      factor kappa B in the livers of the TAA-treated rats, was inhibited by melatonin.
      The hepatic levels of thiobarbituric acid reactive substances, protein carbonyls
      and inducible nitric oxide synthase were lower in the TAA+melatonin-treated group
      (P<0.01), indicating decreased oxidative stress and inflammation. CONCLUSIONS: In
      a rat model of TAA-induced fulminant hepatic failure, melatonin improves survival
      and reduces liver damage and oxidative stress. The results suggest a causative
      role of oxidative stress in TAA-induced hepatic damage and suggest that melatonin
      may be utilized to reduce liver injury associated with oxidative stress.

PMID- 14672619
TI  - Pirfenidone prevents endotoxin-induced liver injury after partial hepatectomy in
      rats.
AB  - BACKGROUND/AIMS: Massive liver resection causes a variety of complications
      including endotoxemia. Pirfenidone (PFD) is a new experimental drug used as
      antifibrotic agent. Studies were performed to investigate whether PFD influences
      the survival rate of animals with endotoxin-induced liver injury after partial
      hepatectomy, and the mechanisms involved. METHODS: Rats were treated with
      lipopolysaccharide (LPS) 48 h after 70% hepatectomy. PFD was administered orally
      before LPS injection. RESULTS: PFD improved the survival rate of LPS-treated rats
      after hepatectomy. PFD prevented increases in serum enzymes and total bilirubin
      related to liver injury. Histopathological analysis revealed that PFD inhibited
      the enhancement in hepatic necrosis and apoptosis. Further, PFD inhibited
      increases of inflammatory cytokines and cytokine-induced neutrophil
      chemoattractant (CINC) in serum and liver, followed by decreases of number of
      infiltrating neutrophils into liver. Electrophoretic mobility shift assay
      revealed that PFD inhibited the activation of transcription factor nuclear factor
      kappa B (NF-kappa B) induced by LPS. PFD also reduced the induction of inducible
      nitric oxide synthase (iNOS) in the liver of LPS-treated rats. CONCLUSIONS: These
      results indicate that PFD inhibits the productions of inflammatory cytokines,
      CINC and iNOS in part through the inhibition of NF-kappa B activation, resulting
      in the prevention of endotoxin-induced liver injury after hepatectomy.

PMID- 14672620
TI  - Ex vivo characterization of tumor-derived melanoma antigen encoding gene-specific
      CD8+cells in patients with hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Members of the melanoma antigen encoding gene family are
      expressed in tumors of different histological types but not in normal tissue. For
      this reason, they are attractive targets for cancer immunotherapy. METHODS: In
      the present study, we analyzed the expression of MAGE-1 and -3 genes in the
      hepatocellular carcinoma (HCC) tissue as well as frequency, phenotype and
      function of circulating and tumor infiltrating CD8+ cells specific for HLA-A1 and
      -A2 restricted epitopes of MAGE-1 and -3. RESULTS: Our study shows for the first
      time the presence of MAGE/tetramer+ CD8 cells in the tumor tissue of patients
      with HCC. These cells are able to recognize the MAGE-1 sequence 161-169 and the
      MAGE-3 sequence 271-279. In a patient with a particularly high frequency of MAGE
      1 sequence 161-169-specific T cells, phenotypic and functional analysis was
      performed showing a phenotype of recently-primed CD8 cells (CD28+CD27+CD45RA
      CCR7). CONCLUSIONS: The observation of a spontaneous in vivo priming of a MAGE
      specific T cell response in patients with HCC and the high frequency of MAGE
      antigens expression in this tumor, makes this antigen a potential candidate for a
      MAGE-specific immunotherapy in hepatocellular carcinoma.

PMID- 14672621
TI  - The regulation of liver regeneration by the plasmin/alpha 2-antiplasmin system.
AB  - BACKGROUND/AIMS: The regeneration after liver injury is regulated by the release
      and activation of several growth factors. The role of the plasmin/alpha(2)
      antiplasmin (alpha(2)-AP) system in liver regeneration was investigated. METHODS:
      CCl(4) was injected intraperitoneally into the mice deficient (-/-) in
      fibrinolytic factors: alpha(2)-AP-/-, plasminogen (Plg) -/-, and Plg-/-.alpha(2)
      AP-/-, and wild-type (WT) mice. The liver tissue was examined for its microscopic
      appearance, fibrinolytic activity, and fibronectin levels. RESULTS: In the gene
      deficient and WT mice, the livers exhibited the same extent of necrosis 2 days
      after the CCl(4) injection. The livers of the WT mice normalized after 7 days,
      and the alpha(2)-AP-/- mice normalized after 5 days. In contrast, the livers of
      the Plg-/- and Plg-/-.alpha(2)-AP-/- mice remained in the damaged state until 14
      days after the liver injury. The injection of anti-alpha(2)-AP antibody in the WT
      mice improved the regeneration after the liver injury, and the injection of
      tranexamic acid in the alpha(2)-AP-/- mice reduced. CONCLUSIONS: These results
      suggest that the plasmin/alpha(2)-AP system played an important role in hepatic
      repair via clearance from the injury area.

PMID- 14672622
TI  - Hexokinase II and VEGF expression in liver tumors: correlation with hypoxia
      inducible factor 1 alpha and its significance.
AB  - BACKGROUND/AIMS: We analyzed the expressions of hexokinase II (HK II), a key
      enzyme in glycolysis, and VEGF in hepatocellular carcinoma (HCC) and metastatic
      liver cancer in relation to tumor vascularity, and the participation of hypoxia
      inducible factor-1 (HIF-1) was studied. METHODS: A real-time quantitative reverse
      transcription-polymerase chain reaction was performed to examine the HK II and
      VEGF mRNA expression. Expression of HIF-1 alpha and HK II protein, and
      microvessel density (MVD) were examined immunohistochemically. RESULTS: MVD was
      significantly higher in HCCs than in metastatic liver cancers, and VEGF mRNA
      expression was positively correlated only with MVD of HCCs. HK II mRNA expression
      was significantly higher in metastatic liver cancers, however, some cases of HCC
      pretreated with transcatheter arterial embolization (TAE) showed marked HK II
      mRNA expression. Both HIF-1 alpha and HK II protein expressions were co-localized
      in the cancer cells near necrosis, and the intensity of HIF-1 alpha protein
      expression was significantly correlated with HK II mRNA expression in both
      tumors. CONCLUSIONS: These results suggest that, in metastatic liver cancers,
      glycolysis induced by HIF-1 is the predominant energy source under the hypoxic
      environment and, at least in some TAE-pretreated HCC cases, cancer cells obtain
      energy for growth by switching the metabolic profile to glycolysis through HIF-1.

PMID- 14672623
TI  - The critical issue of hepatocellular carcinoma prognostic classification: which
      is the best tool available?
AB  - BACKGROUND/AIMS: Prognosis assessment in patients with hepatocellular carcinoma
      (HCC) remains controversial. The most widely used HCC prognostic tool is the
      Okuda classification, but new staging systems (Cancer of the Liver Italian
      Program score, Chinese University Prognostic Index, French classification and
      Barcelona Clinic Liver Cancer, BCLC, staging) have been recently described. We
      investigated the value of known prognostic systems in the particular setting of a
      surgically oriented Liver Unit where 187 HCC Italian patients were mainly treated
      with radical therapies (resection and percutaneous ablation). METHODS: A
      retrospective analysis of 187 HCCs observed at a single Institution from 1990 and
      1999 was performed. By using survival time as the only outcome measure (Kaplan
      Meier method and Cox regression), the performance of any prognostic system was
      assessed according the criteria of discriminatory and stratification abilities
      between different stages, homogeneity of survival within each stage and
      additional explanatory power respect to the other classifications. RESULTS: In
      the particular cohort studied, BCLC proved the best HCC prognostic system. This
      was true for the whole study group and for the 2 subgroups of surgical and non
      surgical patients. CONCLUSIONS: BCLC staging showed the best interpretation of
      the survival distribution in an HCC population comprising a large proportion of
      tumors treated with potentially radical therapies.

PMID- 14672624
TI  - Intracellular trafficking during liver regeneration. Alterations in late
      endocytic and transcytotic pathways.
AB  - BACKGROUND/AIMS: Liver growth, induced by partial hepatectomy of the organ is a
      precisely regulated process during which a radical reorganisation of metabolism
      occurs as the hepatocytes become committed to enter the cell cycle. Recent
      studies have shown the importance of the endocytic compartment in the control of
      lipid and protein intracellular trafficking but also in the control of the signal
      transduction events, which eventually will trigger the initiation of DNA
      synthesis and the subsequent cell division. METHODS: We isolated endosomes at
      different times after partial hepatectomy in male rats and compared with
      endosomes isolated from sham-operated animals. Also, bile was collected and
      analysed by 2D-gel electrophoresis. RESULTS: The amount of late endosomes
      isolated from regenerating livers decreased, concomitant with decreased cathepsin
      D specific enzyme activity. Furthermore, secretion of horseradish peroxidase,
      pIgA and transferrin increased in the pre-replicative phase of liver
      regeneration. CONCLUSIONS: At the early stages of liver regeneration, the
      hepatocellular transport pathway towards degradation (late endosomes and
      lysosomal pathway) decreases, but the transcytosis and the bile secretion of
      several major proteins increases.

PMID- 14672625
TI  - Effects of treatment of hepatorenal syndrome before transplantation on
      posttransplantation outcome. A case-control study.
AB  - BACKGROUND: Pretransplant renal function is the major determinant of survival
      after liver transplantation (LTx). Patients with hepatorenal syndrome (HRS) have
      a poor outcome after LTx compared with patients transplanted without HRS. AIM: To
      analyze the impact of treatment of HRS before LTx on outcome after
      transplantation. METHODS: The outcome of patients with HRS (n=9) treated with
      vasopressin analogues before LTx was compared with that of a contemporary control
      group of patients without HRS (n=27) matched by age, severity of liver failure,
      and type of immunosuppression. RESULTS: Cases and controls were similar with
      respect to pretransplantation characteristics. Three-year survival probability
      was similar between the two groups (HRS-treated: 100% vs control: 83%, P=0.15).
      No significant differences were found between the two groups with respect to the
      incidence of impairment of renal function after LTx (HRS-treated: 22% vs control:
      30%), severe infections (22 vs 33%), acute rejection (33 vs 41%), days in
      Intensive Care Unit (6+/-1 vs 8+/-1), days in hospital (27+/-4 vs 31+/-4), and
      transfusion requirements (11+/-3 vs 10+/-2 units). CONCLUSIONS: Patients with HRS
      treated with vasopressin analogues before LTx have a posttransplantation outcome
      similar to that of patients transplanted with normal renal function. These
      results suggest that HRS should be treated before LTx.

PMID- 14672626
TI  - Overweight and obesity, hepatic steatosis, and progression of chronic hepatitis
      C: a retrospective study on a large cohort of patients in the United States.
AB  - BACKGROUND: Hepatic steatosis has been associated with chronic hepatitis C (CHC),
      but its prevalence, risk factors, and clinical significance remain to be
      determined. AIMS: The present study determined the frequency of, and risk factors
      for hepatic steatosis and its association with activity and progression of CHC in
      a large cohort of U.S. patients. METHODS: This is a retrospective study that
      utilized systematic chart review and statistical analyzes to investigate 324 U.S.
      patients with CHC from a university medical center and a regional VA medical
      center. RESULTS: The frequency of hepatic steatosis was 66.0%. We demonstrated
      that not only being obese, but also overweight (i.e. body mass index > or =25
      kg/m(2)) was independently associated with hepatic steatosis. In our cohort of
      patients with CHC, hepatic steatosis, especially grade II/III steatosis, was
      significantly associated with elevated aspartate aminotransferase at entry,
      persistently elevated alanine aminotransferase, and stage III/IV fibrosis. Grade
      II/III steatosis, was significantly associated with a higher histology activity
      index as well. Multivariate analysis indicated that steatosis, especially grade
      II/III steatosis, was independently associated with stage III/IV fibrosis.
      CONCLUSIONS: Being overweight/obese serves as an independent risk factor for
      hepatic steatosis in U.S. patients with CHC. Steatosis accelerates activity and
      progression of CHC, and is independently associated with stage III/IV hepatic
      fibrosis in these patients.

PMID- 14672627
TI  - MAGE antigens: therapeutic targets in hepatocellular carcinoma?

PMID- 14672628
TI  - The growing evidence that renal function should be improved in patients with
      cirrhosis and hepatorenal syndrome before liver transplantation.

PMID- 14672629
TI  - Magnetic resonance imaging of liver tumors.

PMID- 14672630
TI  - Pharmacological thrombolysis in Budd Chiari syndrome: a single centre experience
      and review of the literature.
AB  - BACKGROUND/AIMS: To review our experience of thrombolytic therapy in patients
      with acute Budd Chiari syndrome (BCS). METHODS: Records of 10 patients with BCS,
      treated by thrombolysis over a 12-year period were retrospectively analysed for
      demographics, clinical presentation/duration, primary disease, thrombolytic
      regimen, and follow-up. The same characteristics were also studied in previously
      reported patients. The agent used was recombinant tissue plasminogen activator
      (tPA) in all patients. RESULTS: Thrombolysis was used 12 times in 10 patients.
      Infusion was made systemically in three patients, into the hepatic artery in one
      patient, locally into a hepatic vein and/or IVC in four patients and locally
      within TIPS/portal vein in two patients. Only one infusion made systemically was
      partially successful. Adjunctive balloon angioplasty and/or stent insertion was
      undertaken for all eight procedures (in six patients) where local infusion was
      into the hepatic vein or TIPS. Six of these were ultimately successful (in five
      patients) and two were unsuccessful. Thrombolysis was more likely to be
      successful in the presence of a short history of thrombosis, when the
      thrombolytic agent was locally infused and when it was combined with a successful
      radiological procedure. Mean follow-up was 4.5 years (range 1-10 years). No
      serious bleeding complication occurred. CONCLUSIONS: We observed no benefit from
      thrombolysis when delivered systemically or arterially except in one case.
      Thrombolysis was useful in adjunctive management of BCS when the drug was infused
      locally into recently thrombosed veins that had appreciable flow following
      partial recanalisation. Thrombolysis was clearly of benefit in the repermeation
      of occluded/partially occluded hepatic veins/TIPS when early detection of new
      thrombus followed interventional procedures such as balloon angioplasty or
      stenting of hepatic veins.

PMID- 14672631
TI  - Hepatic arterial buffer response: visualization by multiphasic high-resolution 3D
      magnetic resonance angiography.

PMID- 14672632
TI  - Lack of detection of novel nonsense mutations on exon 3 of hemochromatosis gene
      in patients with hepatic iron overload.

PMID- 14672633
TI  - Protease inhibitors for treatment of chronic hepatitis C--a new target for the
      magic bullet identified.

PMID- 14672634
TI  - Prevention of HBV reactivation from anti-HBc-positive liver grafts: searching for
      the consensus.

PMID- 14672635
TI  - Food habits, physical activity and body mass index in relation to smoking status
      in 40-42 year old Norwegian women and men.
AB  - BACKGROUND: The aim of the study was to examine the associations between smoking
      habits, and dietary habits, physical activity and body mass index (BMI) in Norway
      in 1997-1999. METHODS: The study was cross-sectional. Data on smoking habits,
      consumption of selected foods and physical activity were collected by
      questionnaire while body height and weight were measured in 59,361 subjects 40-42
      years in 11 Norwegian counties. RESULTS: In both genders, nearly twice as many
      never smokers than current smokers had fruit or vegetables at least twice a day;
      25.5% versus 13.3% for women and 10.5% versus 4.6% for men. The proportion of non
      smoking women with a high intake of fish and fruit/vegetables was considerably
      higher than that of non-smoking men. Mean BMI (95% confidence interval (CI)) was
      higher for never smokers than for current smokers; 25.2 (25.1-25.3) versus 24.7
      (24.6-24.8) kg/m2 for women and 26.6 (26.5-26.7) versus 26.1 (26.0-26.2) kg/m2
      for men. The prevalence of obesity (BMI > or =30 kg/m2) (mean and 95% CI) was
      12.5% (11.9-13.1%) and 14.4% (13.7-15.1%) among never-smoking women and men,
      respectively, whereas in smokers, the prevalence of obesity was 10.3% (9.8-10.8%)
      in women and 12.3% (11.7-12.9%) in men. The prevalence of performing strenuous
      physical activity at least 1 h a week was approximately 10% lower among current
      smokers than among non-smokers for both men and women. CONCLUSION: We found that
      non-smokers had healthier eating habits and higher levels of physical activity
      than did smokers, whereas the prevalence of obesity was lower in smokers. On the
      other hand, there were considerable gender differences, and female smokers'
      eating habits were as healthy as non-smoking males' eating habits.

PMID- 14672636
TI  - Randomised control trial of a smoking cessation intervention directed at men
      whose partners are pregnant.
AB  - BACKGROUND: Although smoking cessation programs significantly reduce smoking
      rates in the general population, some sectors are poorly motivated by them,
      especially healthy men from lower socioeconomic classes. METHODS: By using a
      significant life event (approaching birth of a child) we exploited a time of
      increased receptiveness to smoking cessation influences. A multicomponent
      intervention was conducted and evaluated using a stratified, randomised control
      trial, with an intention to treat analysis. RESULTS: Five hundred and sixty-one
      men were enrolled and 505 (90%) followed to the end of their partners' pregnancy.
      At 6-month follow-up 16.5% of 291 smokers of the intervention group and 9.3% of
      270 in the control group reported they had stopped smoking (P=0.011, OR=0.52, 95%
      CI 0.31 - 0.86). The strongest predictors of smoking cessation were being in a
      skilled occupation, having a higher number of quit attempts in the previous year
      and having the first cigarette of the day relatively later. CONCLUSIONS: The
      number of smoking men who had to be treated to achieve one stopping smoking (NNT)
      during their partner's pregnancy was 13 to 14. Innovative antismoking population
      health measures for the partners of antenatal patients are effective and perhaps
      should be more widely adopted.

PMID- 14672637
TI  - Long-term effects (up to 18 months) of a smoking cessation program among women
      smokers in public health clinics.
AB  - BACKGROUND: We conducted longitudinal analysis of long-term outcomes of a
      motivational smoking cessation program. The program consisted of clinic-based
      minimal interventions delivered to women smokers in public health clinics by
      clinic personnel, a reminder letter, and an optional brief telephone counseling.
      METHODS: Subjects seen in six intervention (N=541) and six control clinics
      (N=527) were interviewed by telephone 2, 6, 12, and 18 months later. At each
      measurement point, unadjusted percent abstinence and mean action, motivation, and
      readiness scores by study group were compared with standard bivariate comparisons
      tests. Hierarchical linear modeling that adjusted for clustering of subjects
      within clinics and clustering of results over 18 months (four waves) within
      individuals was used to compare outcomes by study group. RESULTS: Number of
      actions toward quitting, motivation, and stage of readiness to quit remained
      better in the intervention than in the control group up to 18 months. The program
      effect on abstinence was still significant at 12 months, but not at 18 months.
      CONCLUSIONS: Exposure to one-time, brief interventions in public health clinics
      appears sufficient to enhance abstinence up to 12 months, and action toward
      quitting and motivation and readiness to quit up to 18 months.

PMID- 14672638
TI  - Mammography-facility-based patient reminders and repeat mammograms for Medicare
      in New York State.
AB  - BACKGROUND: Women who receive mammograms may fail to regularly return for repeat
      mammography. Many mammography facilities send annual patient reminders, but there
      are no large studies of their impact on overall mammography return rates, or by
      patient population subgroups. METHODS: Medicare claims data were used to identify
      New York women with claims for mammograms during a baseline and an 18-month
      follow-up period (1999-2000). Receipt of a second mammogram was examined in
      relation to whether the facility sends annual reminders, while controlling for
      other patient factors. RESULTS: Of 97,506 women studied, 76% attended facilities
      that send annual reminders. Of these women, 74% received a second mammogram
      within 18 months compared to 67% for other women. The impact of reminders was
      significant in all subgroups, but was less for women who were younger, minority,
      in Medicaid, in New York City or who received a diagnostic mammogram. In
      multivariate analysis, the adjusted odds ratio for return within 18 months if the
      facility uses reminders was 1.42 (95% CI 1.37-1.47). CONCLUSIONS: Annual patient
      reminders from mammography facilities are effective in increasing regular repeat
      mammography in Medicare women, although their impact is smaller in some groups.
      Facilities that do not currently send reminders should be encouraged to do so.

PMID- 14672639
TI  - Associations between breast cancer risk factors and religious practices in Utah.
AB  - BACKGROUND: Utah has the lowest female malignant breast cancer incidence rates in
      the United States, due in part to low rates among women who are members of the
      Church of Jesus Christ of Latter-day Saints (LDS or Mormon). Several established
      reproductive and non-reproductive breast cancer risk factors may be lower among
      LDS women because of their religious doctrine related to marriage, family, and
      health. This paper investigates the association between selected breast cancer
      risk factors and religious preference and religiosity in Utah. METHODS: A 37-item
      anonymous cross-sectional telephone survey was developed and conducted during
      March and April 2002. Results are based on 848 non-Hispanic white female
      respondents. RESULTS: Number of births (parity), prevalence of breastfeeding, and
      lifetime total duration of breastfeeding were highest among LDS women who
      attended church weekly. Average months of breastfeeding per child were greatest
      among weekly church attendees, regardless of religious preference. Oral
      contraceptive use and total duration of hormone replacement therapy use were
      greatest for individuals of any religion attending church less than weekly and
      for individuals with no religious preference. Comparisons of divergent
      reproductive behaviors between LDS and non-LDS, and between weekly and less than
      weekly church goers, provide strong support for the relatively low breast cancer
      incidence rates previously identified among LDS and, therefore, in Utah.
      CONCLUSIONS: High parity and breastfeeding coincide with comparatively low breast
      cancer incidence rates among LDS and are consistent with recent findings of the
      Collaborative Group on Hormonal Factors in Breast Cancer, showing the primary
      role parity and breastfeeding play in reducing breast cancer.

PMID- 14672640
TI  - Perceptions about the local neighborhood and walking and cycling among children.
AB  - BACKGROUND: This study examined associations between perceptions of the local
      neighborhood and walking and cycling among children. METHODS: Children aged 5-6
      years (n=291) and 10-12 years (n=919) were recruited from 19 Australian primary
      schools. Parents reported their child's usual walking or cycling to local
      destinations and their perceptions of their neighborhood. Ten- to twelve-year
      olds were asked their perceptions of traffic, strangers, road safety and sporting
      venues, and their perceptions of their parent's views on these issues. RESULTS:
      Five- to six-year-old boys whose parents believed there was heavy traffic in
      their area were 2.8 times more likely (95%CI=1.1-6.8), and 5- to 6-year-old girls
      whose parents owned more than one car were 70% less likely (95%CI=0.1-0.8), and
      whose parents believed that public transport was limited in their area were 60%
      less likely (95%CI=0.2-0.9) than other children to walk or cycle at least three
      times per week. Parental belief that there were no lights or crossings was
      associated with walking or cycling among 10- to 12-year-old boys (OR=0.4,
      95%CI=0.2-0.7). Among older girls, parent's belief that their child needed to
      cross several roads to reach play areas (OR=0.4, 95%CI=0.2-0.8) and that there is
      limited public transport in their area (OR=0.7, 95%CI=0.4-0.97), and child's
      belief that there were no parks or sports grounds near home (OR=0.5, 95%CI=0.3
      0.8) were associated with a lower likelihood of walking or cycling. CONCLUSION:
      Perceptions of the local neighborhood may influence children's physical activity.

PMID- 14672641
TI  - Working conditions and health behaviours among employed women and men: the
      Helsinki Health Study.
AB  - BACKGROUND: Working conditions influence health, but previous studies on the
      associations between work-related factors and health behaviours are scarce. The
      aim of this study was to analyse whether unfavourable working conditions are
      associated with diet, physical activity, alcohol consumption, and smoking.
      METHODS: The data derive from postal questionnaires collected in 2000-2001 from
      40- to 60-year-old employees of the City of Helsinki (n=6243, response rate:
      68%). Logistic regression analysis was used to examine health behaviours as
      outcomes. Job demands and job control, physically and mentally strenuous work,
      work fatigue, working overtime and satisfaction with work-home interface were
      independent variables, adjusted for age, education, occupational social class and
      marital status. RESULTS: Most of the examined associations between working
      conditions and health behaviours were not statistically significant. Among women,
      mentally strenuous work and high job control were associated with a healthy diet.
      Work fatigue was associated with physical inactivity, whereas physically
      strenuous work and satisfaction with work-home interface were more often reported
      by physically active women. Work fatigue was associated with high drinking among
      men. Low job strain was reported by nonsmoking women, whereas working overtime
      was associated with nonsmoking among men. CONCLUSIONS: Working conditions were
      only weakly associated with health behaviours, and the associations varied for
      different health behaviours.

PMID- 14672642
TI  - Neighborhood playgrounds, fast food restaurants, and crime: relationships to
      overweight in low-income preschool children.
AB  - BACKGROUND: We examined the relationship between overweight in preschool children
      and three environmental factors--the proximity of the children's residences to
      playgrounds and to fast food restaurants and the safety of the children's
      neighborhoods. We hypothesized that children who lived farther from playgrounds,
      closer to fast food restaurants, and in unsafe neighborhoods were more likely to
      be overweight. METHODS: This was a cross-sectional study of 7,020 low-income
      children, 36 through 59 months of age living in Cincinnati, OH. Overweight was
      defined as a measured body mass index > or =95th percentile. The distance between
      each child's residence and the nearest public playground and fast food restaurant
      was determined with geographic information systems. Neighborhood safety was
      defined by the number of police-reported crimes per 1,000 residents per year in
      each of 46 city neighborhoods. RESULTS: Overall, 9.2% of the children were
      overweight, 76% black, and 23% white. The mean (+/- SD) distances from a child's
      home to the nearest playground and fast food restaurant were 0.31 (+/- 0.22) and
      0.70 (+/- 0.38) miles, respectively. There was no association between child
      overweight and proximity to playgrounds, proximity to fast food restaurants, or
      level of neighborhood crime. The association between child overweight and
      playground proximity did not differ by neighborhood crime level. CONCLUSIONS:
      Within a population of urban low-income preschoolers, overweight was not
      associated with proximity to playgrounds and fast food restaurants or with the
      level of neighborhood crime.

PMID- 14672643
TI  - The contribution of emotional characteristics to breast cancer screening among
      women from six ethnic groups.
AB  - BACKGROUND: This study was designed to determine which of several emotional
      propensities were associated with the frequency of mammograms and clinical breast
      exams among six groups of minority women. Three emotion-related variables that
      have been identified in the previous literature as influencing screening were
      examined: Repression, cancer worry, and embarrassment. However, these variables
      have never been examined within the same study, nor where relevant background
      variables are controlled. METHODS: 1364 African American, US-born white, English
      speaking Caribbean, Haitian, Dominican, and Eastern European women were recruited
      via stratified-cluster sampling. Participants provided demographics and measures
      of beliefs and knowledge. RESULTS: As expected, self-regulation and cancer worry
      were both positively associated with mammogram and clinical breast exam
      frequency, while embarrassment regarding having a mammogram was negatively
      associated with screening. These results held even after controlling for
      demographic variables and the presence or absence of physician recommendation.
      Screening rates for African American women equaled or exceeded the rates for
      European Americans. Other minority subpopulations had even lower screening rates,
      including women from the English-speaking Caribbean and Haitians. CONCLUSIONS:
      Results are discussed in terms of their implications for screening intervention,
      models of health behavior, and the need for more precise operationalizations of
      ethnicity in screening research.

PMID- 14672644
TI  - Home-administered fecal occult blood test for colorectal cancer screening among
      worksites in Taiwan.
AB  - BACKGROUND: This study assessed the perceived acceptance, difficulty level, and
      screening efficacy of home-administered fecal occult blood test (FOBT) among a
      Chinese population. METHODS: Participants (age 40 and above) were recruited at
      various worksites in Taiwan during the summer of 2002. A single group pretest and
      posttest design was used. RESULTS: The 1-month follow up rate was 81% (304/375).
      Screening result return rate (76%) and FOBT completion rate (74%) using the home
      administered kit (HAK) were both high. Intention towards FOBT in the coming year
      significantly increased after the intervention (P<0.001). At pretest,
      participants demonstrated higher perceived acceptance and screening completion
      efficacy of FOBT using home-administered kit (HAK) than the traditional method
      (P<0.001). At posttest, the perceived difficulty of FOBT using HAK was
      significantly lower than the traditional stool-collecting method (P<0.001). While
      the acceptance of HAK remained high both before and after the intervention, the
      acceptance and screening efficacy towards traditional FOBT decreased
      significantly (P<0.001). CONCLUSIONS: This study showed the great potential of
      using home-administered FOBT to promote colorectal cancer (CRC) screening among a
      Chinese population. Future intervention using innovative screening strategies
      will need to consider the participant's stage of adoption and cultural beliefs
      related to screening and preventive behaviors.

PMID- 14672645
TI  - Knowledge of heart attack symptoms in 20 US communities. Results from the Rapid
      Early Action for Coronary Treatment Community Trial.
AB  - BACKGROUND: Effective treatment for patients with acute myocardial infarction is
      limited by patient delay in seeking care. Inadequate knowledge of heart attack
      symptoms may prolong delay. An intervention designed to reduce delay was tested
      in the Rapid Early Action for Coronary Treatment (REACT) Community Trial. In this
      report, the impact on knowledge of heart attack symptoms is presented. METHODS:
      Twenty communities were randomized to intervention or comparison status in a
      matched-pair design. Intervention strategies included community organization,
      public education, professional education, and patient education. The main outcome
      measures were based on information regarding knowledge of symptoms collected in a
      series of four random-digit-dialed telephone surveys. RESULTS: Knowledge of REACT
      targeted symptoms increased in intervention communities. No change was observed
      in comparison communities. The net effect was an increase of 0.44 REACT-targeted
      symptoms per individual (P<0.001). The intervention effect was greater in ethnic
      minorities, persons with lower household incomes, and those with family or spouse
      history of heart attack (P<0.05). CONCLUSIONS: The REACT intervention was
      modestly successful in increasing the general public's knowledge of the complex
      constellation of heart attack symptoms. The intervention program was somewhat
      more effective in reaching disadvantaged subgroups, including ethnic minorities
      and persons with lower income. Despite these successes, the post-intervention
      level of knowledge was suboptimal.

PMID- 14672646
TI  - Association of physical activity intensity levels with overweight and obesity in
      a population-based sample of adults.
AB  - BACKGROUND: Clarify the association between physical activity intensity and
      overweight/obesity. METHODS: Population-based 1997-2001 survey in Geneva,
      Switzerland (n=5,757, ages 35 to 74). Intensity of physical activity energy
      expenditure (EE) defined as percentage of total EE in moderate activities [3-3.9
      x basal metabolism rate (BMR), e.g., normal walking, household chores] and high
      intensity activities (> or =4 x BMR, e.g., brisk walking, sports). Overweight or
      obesity based on measured body mass index (BMI). RESULTS: Comparing participants
      in the lowest vs. the highest tertile of the percentage of high-intensity EE, the
      odds ratios (ORs) were, for obesity vs. normal weight, 2.8 (95% confidence
      interval: 2.0-3.8, P<0.0001) in men and 2.4 (1.7-3.4, P<0.0001) in women. For
      obese vs. overweight, the men/women ORs were 1.9 (1.4-2.6, P<0.0001)/1.5 (1.0
      2.2, P<0.05). For overweight vs. normal weight, the men/women ORs were 1.4 (1.1
      1.7, P<0.002)/1.7 (1.3-2.1, P<0.0001). Less or no relationship was found for the
      percentage of moderate-intensity EE. CONCLUSIONS: This cross-sectional study
      cannot determine whether exercise is an effective strategy for weight control or
      whether overweight or obese people exercise less. However, clear dose-response
      associations in both genders between obesity or overweight and energy expenditure
      in high (but not in moderate)-intensity activities are findings with potentially
      major public health implications meriting validation in an experimental
      intervention study.

PMID- 14672647
TI  - Correlates of underutilization of gynecological cancer screening among lesbian
      and heterosexual women.
AB  - BACKGROUND: Study aims were to examine cervical cancer risk factors, screening
      patterns, and predictors of screening adherence in demographically similar
      samples of lesbian (N=550) and heterosexual women (N=279). METHODS: Data are from
      a multisite survey study of women's health conducted from 1994 to 1996. RESULTS:
      Differences in sexual behavior risk factors for cervical cancer were observed
      with lesbians reporting earlier onset of sexual activity (P<0.05), more sexual
      partners (P<0.001), and lower use of safer sex activities (P<0.01). Lesbian and
      heterosexual women were equally likely to have ever had a Pap test; however,
      lesbians were less likely to report annual (P<0.001) or routine (P<0.001)
      testing. Multivariate analyses were used to determine the associations between
      demographics, health care factors, health behaviors, and worry about health and
      screening behaviors. Individual predictors of never screening included younger
      age, lower income, and lack of annual medical visits. Independent predictors of
      both recent and annual screenings included history of an abnormal Pap test, being
      heterosexual, and annual medical visits. CONCLUSION: Data indicate that lesbians
      are at risk for cervical cancer, yet underutilize recommended screening tests.
      Findings have implications for research, education, and cancer control among
      lesbians.

PMID- 14672648
TI  - Smoking patterns in a community sample of Portuguese adults, 1999-2000.
AB  - BACKGROUND: Southern European cultural specificities might influence the dynamic
      of the tobacco epidemic. Thus, we aimed to evaluate the distribution and
      determinants of smoking patterns in an urban Portuguese population. METHODS: We
      evaluated 1,644 community dwellers (1,015 women, 629 men) using a structured
      questionnaire, comprising social, behavioral, and clinical information. Number of
      cigarettes smoked, age at smoking initiation, and quitting were self-reported.
      Proportions were age adjusted for the European population and the magnitude of
      associations computed using logistic regression. RESULTS: Smoking was more common
      in younger, unemployed, normal weighted, and less physically active men. Female
      smoking prevalence was higher in younger, more educated, and overweight. Compared
      to females, males had a higher prevalence of smoking (35.0%; 95% confidence
      intervals [CI] 31.3-38.8 vs. 17.6%; 95% CI 15.4-20.1; P<0.001), a higher mean
      number of cigarettes smoked (21.2; 95% CI 12.4-15.0 vs. 14.1; 95% CI 19.6-22.6;
      P<0.001), and a higher proportion began smoking before 18 years of age (60.1%;
      95% CI 55.5-64.5 vs. 42.6%; 95% CI 36.9-48.5; P<0.001). CONCLUSION: Among
      Portuguese, adults smoking remains more frequent in men but the prevalence is
      reaching a disturbing proportion in women, especially young and more educated.
      This smoking pattern places Portugal in stage 2 of smoking epidemic.

PMID- 14672649
TI  - MosA, a protein implicated in rhizopine biosynthesis in Sinorhizobium meliloti L5
      30, is a dihydrodipicolinate synthase.
AB  - MosA is a gene product encoded on a pSym megaplasmid of Sinorhizobium meliloti L5
      30. The gene is part of an operon reported to be essential for the synthesis of
      the rhizopine 3-O-methyl-scyllo-inosamine. MosA has been assigned the function of
      an O-methyltransferase. However, the reported sequence of this protein is very
      much like that of dihydrodipicolinate synthase (DHDPS), except for a 40 amino
      acid residue C-terminal domain. This similarity contradicts accepted ideas
      regarding structure-function relationships of enzymes. We have cloned and
      overexpressed the recombinant gene in Escherichia coli, and discovered that the
      reported sequence contains an error resulting in a frame-shift. The correct
      sequence contains a new stop codon, truncating the C-terminal 41 amino acid
      residues of the reported sequence. The expressed protein, bearing an N-terminal
      polyhistidine tag, catalyzes the condensation of pyruvate and aspartate beta
      semialdehyde efficiently, suggesting that this activity is not a side-reaction,
      but an activity for which this enzyme has evolved. Electro-spray mass
      spectrometry experiments and inhibition by L-lysine are consistent with the
      enzyme being a DHDPS. E.coli AT997, a mutant host normally requiring exogenous
      diaminopimelate for growth, could be complemented by transformation with a
      plasmid bearing the gene encoding MosA. A role for this enzyme in rhizopine
      synthesis cannot be ruled out, but is called into question.

PMID- 14672650
TI  - Recognition of 5'-YpG-3' sequences by coupled stacking/hydrogen bonding
      interactions with amino acid residues.
AB  - The combined biochemical and structural study of hundreds of protein-DNA
      complexes has indicated that sequence-specific interactions are mediated by two
      mechanisms termed direct and indirect readout. Direct readout involves direct
      interactions between the protein and base-specific atoms exposed in the major and
      minor grooves of DNA. For indirect readout, the protein recognizes DNA by sensing
      conformational variations in the structure dependent on nucleotide sequence,
      typically through interactions with the phosphodiester backbone. Based on our
      recent structure of Ndt80 bound to DNA in conjunction with a search of the
      existing PDB database, we propose a new method of sequence-specific recognition
      that utilizes both direct and indirect readout. In this mode, a single amino acid
      side-chain recognizes two consecutive base-pairs. The 3'-base is recognized by
      canonical direct readout, while the 5'-base is recognized through a variation of
      indirect readout, whereby the conformational flexibility of the particular
      dinucleotide step, namely a 5'-pyrimidine-purine-3' step, facilitates its
      recognition by the amino acid via cation-pi interactions. In most cases, this
      mode of DNA recognition helps explain the sequence specificity of the protein for
      its target DNA.

PMID- 14672651
TI  - The herpes simplex virus processivity factor, UL42, binds DNA as a monomer.
AB  - The processivity subunit of the herpes simplex virus DNA polymerase, UL42, is a
      monomer in solution. However, UL42 is structurally similar to sliding clamp
      processivity factors, such as PCNA, which encircle DNA as a multimeric ring. We
      used chemical crosslinking and electrophoretic mobility-shift assays to
      investigate whether UL42 oligomerizes upon DNA binding. UL42 did not form
      intermolecular crosslinks upon treatment with glutaraldehyde in the presence of
      DNA, whereas proteins that are known to be multimers in solution were
      successfully crosslinked by this treatment. This result suggests that UL42 does
      not form multimers on DNA. We next analyzed the composition of UL42:DNA complexes
      using electrophoretic mobility-shift assays. UL42 was mixed with a maltose
      binding protein-UL42 fusion protein before being added to DNA. The patterns of
      electrophoretic mobility of the resultant protein:DNA complexes were those
      predicted if each isoform of UL42 binds to DNA as a monomer. From this result and
      the failure of UL42 to form crosslinks, we infer that UL42 binds DNA as a
      monomer.

PMID- 14672652
TI  - Dephosphorylation of RNA polymerase II by CTD-phosphatase FCP1 is inhibited by
      phospho-CTD associating proteins.
AB  - Reversible phosphorylation of the repetitive C-terminal domain (CTD) of the
      largest RNA polymerase (RNAP) II subunit plays a key role in the progression of
      RNAP through the transcription cycle. The level of CTD phosphorylation is
      determined by multiple CTD kinases and a CTD phosphatase, FCP1. The
      phosphorylated CTD binds to a variety of proteins including the cis/trans
      peptidyl-prolyl isomerase (PPIase) Pin1 and enzymes involved in processing of the
      primary transcript such as the capping enzyme Hce1 and CA150, a nuclear factor
      implicated in transcription elongation. Results presented here establish that the
      dephosphorylation of hyperphosphorylated RNAP II (RNAP IIO) by FCP1 is impaired
      in the presence of Pin1 or Hce1, whereas CA150 has no influence on FCP1 activity.
      The inhibition of dephosphorylation is observed with free RNAP IIO generated by
      different CTD kinases as well as with RNAP IIO engaged in an elongation complex.
      These findings support the idea that specific phospho-CTD associating proteins
      can differentially modulate the dephosphorylation of RNAP IIO by steric hindrance
      and may play an important role in the regulation of gene expression.

PMID- 14672653
TI  - Redox-dependent changes in RsrA, an anti-sigma factor in Streptomyces coelicolor:
      zinc release and disulfide bond formation.
AB  - sigmaR is a sigma factor for transcribing genes to defend cells against oxidative
      stresses in the antibiotic-producing bacterium Streptomyces coelicolor. The
      availability of sigmaR is regulated by RsrA, an anti-sigma factor, whose sigmaR
      binding activity is regulated by redox changes in the environment, via thiol
      disulfide exchange. We found that reduced RsrA contains zinc in a stoichiometric
      amount, whereas oxidized form has very little: 1 mol of zinc per mol of RsrA was
      released upon oxidation as monitored by a chromogenic Zn-chelator, 4-(2
      pyridylazo)-resorcinol (PAR). Measurement of zinc bound in several RsrA mutants
      of various cysteine and histidine substitutions suggested that C3, H7, C41, and
      C44 serve as zinc-binding sites. The zinc-binding and sigmaR-binding activities
      of mutant proteins did not coincide, suggesting that zinc might not be absolutely
      required for the anti-sigma activity of RsrA. Zn-free apo-RsrA bound sigmaR and
      inhibited sigmaR-dependent transcription in vitro. Compared with Zn-RsrA, the
      anti-transcription activity of apo-RsrA was about threefold lower and its sigmaR
      binding affinity decreased by about ninefold when measured by surface plasmon
      resonance analysis. Apo-RsrA was more sensitive to protease, suggesting that zinc
      allows RsrA to maintain a more compact structure, optimized for binding sigmaR.
      The cysteine pairs that form disulfide bonds were determined by MALDI-TOF mass
      spectrometry, revealing formation of the critical disulfide bond between C11 and
      one of the essential cysteine residues C41 or 44, most likely C44. An improved
      model for the mechanism of redox-modulation of RsrA was presented.

PMID- 14672655
TI  - Interaction with capsid protein alters RNA structure and the pathway for in vitro
      assembly of cowpea chlorotic mottle virus.
AB  - Viruses use sophisticated mechanisms to allow the specific packaging of their
      genome over that of host nucleic acids. We examined the in vitro assembly of the
      Cowpea chlorotic mottle virus (CCMV) and observed that assembly with viral RNA
      follows two different mechanisms. Initially, CCMV capsid protein (CP) dimers bind
      RNA with low cooperativity and form virus-like particles of 90 CP dimers and one
      copy of RNA. Longer incubation reveals a different assembly path. At a
      stoichiometry of about ten CP dimers per RNA, the CP slowly folds the RNA into a
      compact structure that can be bound with high cooperativity by additional CP
      dimers. This folding process is exclusively a function of CP quaternary structure
      and is independent of RNA sequence. CP-induced folding is distinct from RNA
      folding that depends on base-pairing to stabilize tertiary structure. We
      hypothesize that specific encapsidation of viral RNA is a three-step process:
      specific binding by a few copies of CP, RNA folding, and then cooperative binding
      of CP to the "labeled" nucleoprotein complex. This mechanism, observed in a plant
      virus, may be applicable to other viruses that do not halt synthesis of host
      nucleic acid, including HIV.

PMID- 14672654
TI  - Functional activity of eukaryotic signal sequences in Escherichia coli: the
      ovalbumin family of serine protease inhibitors.
AB  - It is widely assumed that the functional activity of signal sequences has been
      conserved throughout evolution, at least between Gram-negative bacteria and
      eukaryotes. The ovalbumin family of serine protease inhibitors (serpins) provides
      a unique tool to test this assumption, since individual members can be secreted
      (ovalbumin), cytosolic (leukocyte elastase inhibitor, LEI), or targeted to both
      compartments (plasminogen activator inhibitor 2, PAI-2). The facultative
      secretion of PAI-2 is mediated by a signal sequence proposed to be inefficient by
      design. We show here that the same internal domain that promotes an inefficient
      translocation of murine PAI-2 in mammalian cells is a weak signal sequence in
      Escherichia coli. In contrast, the ovalbumin signal sequence is much more
      efficient, whereas the corresponding sequence elements from LEI, maspin and PI-10
      are entirely devoid of signal sequence activity in E.coli. Mutations that improve
      the activity of the PAI-2 signal sequence and that convert the N-terminal regions
      of maspin and PI-10 into efficient signal sequences have been characterized.
      Taken together, these results indicate that several structural features
      contribute to the weak activity of the PAI-2 signal sequence and provide new
      insights into the plasticity of the "hydrophobic core" of signal sequences. High
      level expression of two chimeric proteins containing the PAI-2 signal sequence is
      toxic, and the reduced viability is accompanied by a rapid decrease in the
      membrane proton motive force, in ATP levels and in translation. In unc- cells,
      which lack the F0F1 ATP-synthase, the chimeric proteins retain their toxicity and
      their expression only affected the proton motive force. Thus, the properties of
      these toxic signal sequences offer a new tool to dissect the interactions of
      signal sequences with the protein export machinery.

PMID- 14672656
TI  - Altering the RNA-binding mode of the U1A RBD1 protein.
AB  - The N-terminal RNA-binding domain (RBD1) of the human U1A protein is
      evolutionarily designed to bind its RNA targets with great affinity and
      specificity. The physical mechanisms that modulate the coupling (local
      cooperativity) among amino acid residues on the extensive binding surface of RBD1
      are investigated here, using mutants that replace a highly conserved glycine
      residue. This glycine residue, at the strand/loop junction of beta3/loop3, is
      found in U1A RBD1, and in most RBD domains, suggesting it has a specific role in
      modulation of RNA binding. Here, two RBD1 proteins are constructed in which that
      residue (Gly53) is replaced by either alanine or valine. These new proteins are
      shown by NMR methods and molecular dynamics simulations to be very similar to the
      wild-type RBD1, both in structure and in their backbone dynamics. However, RNA
      binding assays show that affinity for the U1 snRNA stem-loop II RNA target is
      reduced by nearly 200-fold for the RBD1-G53A protein, and by 1.6 x 10(4)-fold for
      RBD1-G53V. The mode of RNA binding by RBD1-G53A is similar to that of RBD1-WT,
      displaying its characteristic non-additive free energies of base recognition and
      its salt-dependence. The binding mode of RBD1-G53V is altered, having lost its
      salt-dependence and displaying site-independence of base recognition. The
      molecular basis for this alteration in RNA-binding properties is proposed to
      result from the inability of the RNA to induce a change in the structure of the
      free protein to produce a high-affinity complex.

PMID- 14672657
TI  - Two positively charged residues of phi29 DNA polymerase, conserved in protein
      primed DNA polymerases, are involved in stabilisation of the incoming nucleotide.
AB  - In DNA polymerases from families A and B in the closed conformation, several
      positively charged residues, located in pre-motif B and motif B, have been shown
      to interact with the phosphate groups of the incoming nucleotide at the
      polymerisation active site: the invariant Lys of motif B and the nearly invariant
      Lys of pre-motif B (family B) correspond to a His in family A DNA polymerases. In
      phi29 DNA polymerase, belonging to the family B DNA polymerases able to start
      replication by protein-priming, the corresponding residues, Lys383 and Lys371,
      have been shown to be dNTP-ligands. Since in several DNA polymerases a third
      residue has been involved in dNTP binding, we have addressed here the question if
      in the DNA polymerases of the protein-primed subfamily, and especially in phi29
      DNA polymerase, there are more than these two residues involved in nucleotide
      binding. By site-directed mutagenesis in phi29 DNA polymerase the functional role
      of the remaining two conserved positively charged amino acid residues of pre
      motif B and motif B (besides Lys371 and Lys383) has been studied. The results
      indicate that residue Lys379 of motif B is also involved in dNTP binding,
      possibly through interaction with the triphosphate moiety of the incoming
      nucleotide, since the affinity for nucleotides of mutant DNA polymerase K379T was
      reduced in DNA and TP-primed reactions. On the other hand, we propose that, when
      the terminal protein (TP) is present at the polymerisation active site, residue
      Lys366 of pre-motif B is involved in stabilising the incoming nucleotide in an
      appropriate position for efficient TP-deoxynucleotidylation. Although mutant DNA
      polymerase K366T showed a wild-type like phenotype in DNA-primed polymerisation
      in the presence of DNA as template, in TP-primed reactions as initiation and
      transition it was impaired, especially in the presence of the phi29 DBP, protein
      p6.

PMID- 14672658
TI  - Alternative splicing mechanisms for the modulation of protein function:
      conservation between human and other species.
AB  - Alternative splicing (AS) is an important process in eukaryotic organisms by
      which a given gene may express a set of different protein isoforms depending on
      the tissue, or the developmental stage of the individual. In the present work, we
      have compared AS among species, focusing on the conservation of AS mechanisms for
      the modulation of protein function. For this purpose, we first analysed the
      frequency with which different species, human, mouse, rat and fruitfly, utilise
      them. Second, we focused more directly on the conservation among species of the
      mechanisms themselves. To this end, we compared biologically equivalent AS events
      between human and mouse, or rat. Our results indicate only minor differences in
      the frequency of use of these mechanisms, as well as a high degree of
      conservation among the species studied.

PMID- 14672659
TI  - The 2.0 A resolution crystal structure of prostaglandin H2 synthase-1: structural
      insights into an unusual peroxidase.
AB  - Prostaglandin H2 synthase (EC 1.14.99.1) is an integral membrane enzyme
      containing a cyclooxygenase site, which is the target for the non-steroidal anti
      inflammatory drugs, and a spatially distinct peroxidase site. Previous
      crystallographic studies of this clinically important drug target have been
      hindered by low resolution. We present here the 2.0 A resolution X-ray crystal
      structure of ovine prostaglandin H2 synthase-1 in complex with alpha-methyl-4
      biphenylacetic acid, a defluorinated analog of the non-steroidal anti
      inflammatory drug flurbiprofen. Detergent molecules are seen to bind to the
      protein's membrane-binding domain, and their positions suggest the depth to which
      this domain is likely to penetrate into the lipid bilayer. The relation of the
      enzyme's proximal heme ligand His388 to the heme iron is atypical for a
      peroxidase; the iron-histidine bond is unusually long and a substantial tilt
      angle is observed between the heme and imidazole planes. A molecule of glycerol,
      used as a cryoprotectant during diffraction experiments, is seen to bind in the
      peroxidase site, offering the first view of any ligand in this active site.
      Insights gained from glycerol binding may prove useful in the design of a
      peroxidase-specific ligand.

PMID- 14672660
TI  - The structure of Mycobacterium tuberculosis MPT51 (FbpC1) defines a new family of
      non-catalytic alpha/beta hydrolases.
AB  - Mycobacterium tuberculosis, the causative agent of tuberculosis, is known to
      secrete a number of highly immunogenic proteins that are thought to confer
      pathogenicity, in part, by mediating binding to host tissues. Among these
      secreted proteins are the trimeric antigen 85 (Ag85) complex and the related
      MPT51 protein, also known as FbpC1. While the physiological function of Ag85, a
      mycolyltransferase required for the biosynthesis of the cell wall component
      alpha,alpha'-trehalose dimycolate (or cord factor), has been identified recently,
      the function of the closely related MPT51 (approximately 40% identity with the
      Ag85 components) remains to be established. The crystal structure of
      M.tuberculosis MPT51, determined to 1.7 A resolution, shows that MPT51, like the
      Ag85 components Ag85B and Ag85C2, folds as an alpha/beta hydrolase, but it does
      not contain any of the catalytic elements required for mycolyltransferase
      activity. Moreover, the absence of a recognizable alpha,alpha'-trehalose
      monomycolate-binding site and the failure to detect an active site suggest that
      the function of MPT51 is of a non-enzymatic nature and that MPT51 may in fact
      represent a new family of non-catalytic alpha/beta hydrolases. Previous
      experimental evidence and the structural similarity to some integrins and
      carbohydrate-binding proteins led to the hypothesis that MPT51 might have a role
      in host tissue attachment, whereby ligands may include the serum protein
      fibronectin and small sugars.

PMID- 14672661
TI  - Crystal structure of the L intermediate of bacteriorhodopsin: evidence for
      vertical translocation of a water molecule during the proton pumping cycle.
AB  - For structural investigation of the L intermediate of bacteriorhodopsin, a 3D
      crystal belonging to the space group P622 was illuminated with green light at 160
      K and subsequently with red light at 100 K. This yielded a approximately 1:4
      mixture of the L intermediate and the ground-state. Diffraction data from such
      crystals were collected using a low flux of X-rays ( approximately 2 x 10(15)
      photons/mm2 per crystal), and their merged data were compared with those from
      unphotolyzed crystals. These structural data, together with our previous data,
      indicate that the retinal chromophore, which is largely twisted in the K
      intermediate, takes a more planar 13-cis, 15-anti configuration in the L
      intermediate. This configurational change, which is accompanied by re-orientation
      of the Schiff base N-H bond towards the intracellular side, is coupled with a
      large rotation of the side-chain of an amino acid residue (Leu93) making contact
      with the C13 methyl group of retinal. Following these motions, a water molecule,
      at first hydrogen-bonded to the Schiff base and Asp85, is dragged to a space that
      is originally occupied by Leu93. Diffraction data from a crystal containing the M
      intermediate showed that this water molecule moves further towards the
      intracellular side in the L-to-M transition. It is very likely that detachment of
      this water molecule from the protonated Schiff base causes a significant decrease
      in the pKa of the Schiff base, thereby facilitating the proton transfer to Asp85.
      On the basis of these observations, we argue that the vertical movement of a
      water molecule in the K-to-L transition is a key event determining the
      directionality of proton translocation in the protein.

PMID- 14672662
TI  - Inhibition of a mitotic motor protein: where, how, and conformational
      consequences.
AB  - We report here the first inhibitor-bound structure of a mitotic motor protein.
      The 1.9 A resolution structure of the motor domain of KSP, bound with the small
      molecule monastrol and Mg2+ x ADP, reveals that monastrol confers inhibition by
      "induced-fitting" onto the protein some 12 A away from the catalytic center of
      the enzyme, resulting in the creation of a previously non-existing binding
      pocket. The structure provides new insights into the biochemical and mechanical
      mechanisms of the mitotic motor domain. Inhibition of KSP provides a novel
      mechanism to arrest mitotic spindle formation, a target of several approved and
      investigative anti-cancer agents. The structural information gleaned from this
      novel pocket offers a new angle for the design of anti-mitotic agents.

PMID- 14672663
TI  - Symmetric K+ and Mg2+ ion-binding sites in the 5S rRNA loop E inferred from
      molecular dynamics simulations.
AB  - Potassium binding to the 5S rRNA loop E motif has been studied by molecular
      dynamics at high (1.0 M) and low (0.2 M) concentration of added KCl in the
      presence and absence of Mg2+. A clear pattern of seven deep groove K+ binding
      sites or regions, in all cases connected with guanine N7/O6 atoms belonging to
      GpG, GpA, and GpU steps, was identified, indicating that the LE deep groove is
      significantly more ionophilic than the equivalent groove of regular RNA duplexes.
      Among all, two symmetry-related sites (with respect to the central G.A pair) were
      found to accommodate K+ ions with particularly long residence times. In a
      preceding molecular dynamics study by Auffinger et al. in the year 2003, these
      two sites were described as constituting important Mg2+ binding locations.
      Altogether, the data suggest that these symmetric sites correspond to the loop E
      main ion binding regions. Indeed, they are located in the deep groove of an
      important ribosomal protein binding motif associated with a fragile pattern of
      non-Watson-Crick pairs that has certainly to be stabilized by specific Mg2+ ions
      in order to be efficiently recognized by the protein. Besides, the other sites
      accommodate monovalent ions in a more diffuse way pointing out their lesser
      significance for the structure and function of this motif. Ion binding to the
      shallow groove and backbone atoms was generally found to be of minor importance
      since, at the low concentration, no well defined binding site could be
      characterized while high K+ concentration promoted mostly unspecific potassium
      binding to the RNA backbone. In addition, several K+ binding sites were located
      in positions equivalent to water molecules from the first hydration shell of
      divalent ions in simulations performed with magnesium, indicating that ion
      binding regions are able to accommodate both mono- and divalent ionic species.
      Overall, the simulations provide a more precise but, at the same time, a more
      intricate view of the relations of this motif with its ionic surrounding.

PMID- 14672664
TI  - The 3D solution structure of the C-terminal region of Ku86 (Ku86CTR).
AB  - In eukaryotes the non-homologous end-joining repair of double strand breaks in
      DNA is executed by a series of proteins that bring about the synapsis,
      preparation and ligation of the broken DNA ends. The mechanism of this process
      appears to be initiated by the obligate heterodimer (Ku70/Ku86) protein complex
      Ku that has affinity for DNA ends. Ku then recruits the DNA-dependent protein
      kinase catalytic subunit (DNA-PKcs). The three-dimensional structures of the
      major part of the Ku heterodimer, representing the DNA-binding core, both free
      and bound to DNA are known from X-ray crystallography. However, these structures
      lack a region of ca 190 residues from the C-terminal region (CTR) of the Ku86
      subunit (also known as Lupus Ku autoantigen p86, Ku80, or XRCC5) that includes
      the extreme C-terminal tail that is reported to be sufficient for DNA-PKcs
      binding. We have examined the structural characteristics of the Ku86CTR protein
      expressed in bacteria. By deletion mutagenesis and heteronuclear NMR spectroscopy
      we localised a globular domain consisting of residues 592-709. Constructs
      comprising additional residues either to the N-terminal side (residues 543-709),
      or the C-terminal side (residues 592-732), which includes the putative DNA-PKcs
      binding motif, yielded NMR spectra consistent with these extra regions lacking
      ordered structure. The three-dimensional solution structure of the core globular
      domain of the C-terminal region of Ku86 (Ku86CTR(592-709)) has been determined
      using heteronuclear NMR spectroscopy and dynamical simulated annealing using
      structural restraints from nuclear Overhauser effect spectroscopy, and scalar and
      residual dipolar couplings. The polypeptide fold comprises six regions of alpha
      helical secondary structure that has an overall superhelical topology remotely
      homologous to the MIF4G homology domain of the human nuclear cap binding protein
      80 kDa subunit and the VHS domain of the Drosophila protein Hrs, though strict
      analysis of the structures suggests that these domains are not functionally
      related. Two prominent hydrophobic pockets in the gap between helices alpha2 and
      alpha4 suggest a potential ligand-binding characteristic for this globular
      domain.

PMID- 14672665
TI  - The "rhodanese" fold and catalytic mechanism of 3-mercaptopyruvate
      sulfurtransferases: crystal structure of SseA from Escherichia coli.
AB  - 3-Mercaptopyruvate sulfurtransferases (MSTs) catalyze, in vitro, the transfer of
      a sulfur atom from substrate to cyanide, yielding pyruvate and thiocyanate as
      products. They display clear structural homology with the protein fold observed
      in the rhodanese sulfurtransferase family, composed of two structurally related
      domains. The role of MSTs in vivo, as well as their detailed molecular mechanisms
      of action have been little investigated. Here, we report the crystal structure of
      SseA, a MST from Escherichia coli, which is the first MST three-dimensional
      structure disclosed to date. SseA displays specific structural differences
      relative to eukaryotic and prokaryotic rhodaneses. In particular, conformational
      variation of the rhodanese active site loop, hosting the family invariant
      catalytic Cys residue, may support a new sulfur transfer mechanism involving
      Cys237 as the nucleophilic species and His66, Arg102 and Asp262 as residues
      assisting catalysis.

PMID- 14672666
TI  - Structural and functional studies of FkpA from Escherichia coli, a cis/trans
      peptidyl-prolyl isomerase with chaperone activity.
AB  - The protein FkpA from the periplasm of Escherichia coli exhibits both cis/trans
      peptidyl-prolyl isomerase (PPIase) and chaperone activities. The crystal
      structure of the protein has been determined in three different forms: as the
      full-length native molecule, as a truncated form lacking the last 21 residues,
      and as the same truncated form in complex with the immunosuppressant ligand,
      FK506. FkpA is a dimeric molecule in which the 245-residue subunit is divided
      into two domains. The N-terminal domain includes three helices that are
      interlaced with those of the other subunit to provide all inter-subunit contacts
      maintaining the dimeric species. The C-terminal domain, which belongs to the
      FK506-binding protein (FKBP) family, binds the FK506 ligand. The overall form of
      the dimer is V-shaped, and the different crystal structures reveal a flexibility
      in the relative orientation of the two C-terminal domains located at the
      extremities of the V. The deletion mutant FkpNL, comprising the N-terminal domain
      only, exists in solution as a mixture of monomeric and dimeric species, and
      exhibits chaperone activity. By contrast, a deletion mutant comprising the C
      terminal domain only is monomeric, and although it shows PPIase activity, it is
      devoid of chaperone function. These results suggest that the chaperone and
      catalytic activities reside in the N and C-terminal domains, respectively.
      Accordingly, the observed mobility of the C-terminal domains of the dimeric
      molecule could effectively adapt these two independent folding functions of FkpA
      to polypeptide substrates.

PMID- 14672667
TI  - Destabilization of the Escherichia coli RNase H kinetic intermediate: switching
      between a two-state and three-state folding mechanism.
AB  - Escherichia coli RNase H folds through a partially folded kinetic intermediate
      that mirrors a rarely populated, partially unfolded form detectable by native
      state hydrogen exchange under equilibrium conditions. Residue 53 is at the
      interface of two helices known to be structured in this intermediate. Kinetic
      refolding studies on mutant proteins varying in size and hydrophobicity at
      residue 53 support a contribution of hydrophobicity to the stabilities of the
      kinetic intermediate and the transition state. Packing interactions also play a
      significant role in the stability of these two states, though they play a much
      larger role in the native-state stability. One dramatic mutation, I53D, results
      in the conversion from a three-state to a two-state folding mechanism, which is
      explained most easily through a simple destabilization of the kinetic
      intermediate such that it is no longer stable with respect to the unfolded state.
      These results demonstrate that interactions that stabilize an intermediate can
      accelerate folding if these same interactions are present in the transition
      state. Our results are consistent with a hierarchical model of folding, where the
      intermediate consists of native-like interactions, is on-pathway, and is
      productive for folding.

PMID- 14672668
TI  - The tryptophan switch: changing ligand-binding specificity from type I to type II
      in SH3 domains.
AB  - The ability of certain Src homology 3 (SH3) domains to bind specifically both
      type I and type II polyproline ligands is perhaps the best characterized, but
      also the worst understood, example in the family of protein-interaction modules.
      A detailed analysis of the structural variations in SH3 domains, with respect to
      ligand-binding specificity, together with mutagenesis of SH3 Fyn tyrosine kinase,
      reveal the structural basis for types I and II binding specificity by SH3
      domains. The conserved Trp in the SH3 binding pocket can adopt two different
      orientations that, in turn, determine the type of ligand (I or II) able to bind
      to the domain. The only exceptions are ligands with Leu at positions P(-1) and
      P(2), that deviate from standard poly-Pro angles. The motion of the conserved Trp
      depends on the presence of certain residues located in a key position (132 for
      Fyn), near the binding pocket. SH3 domains placing aromatic residues in this key
      position are promiscuous. By contrast, those presenting beta-branched or long
      aliphatic residues block the conserved Trp in one of the two possible
      orientations, preventing binding in a type I orientation. This is experimentally
      demonstrated by a single mutation in Fyn SH3 (Y132I) that abolishes type I ligand
      binding, while preserving binding to type II ligands. Thus, simple conformational
      changes, governed by simple rules, can have profound effects on protein-protein
      interactions, highlighting the importance of structural details to predict
      protein-protein interactions.

PMID- 14672669
TI  - Influence of proline residues in transmembrane helix packing.
AB  - Integral membrane proteins often contain proline residues in their alpha-helical
      transmembrane (TM) fragments, which may strongly influence their folding and
      association. Pro-scanning mutagenesis of the helical domain of glycophorin A
      (GpA) showed that replacement of the residues located at the center abrogates
      helix packing while substitution of the residues forming the ending helical turns
      allows dimer formation. Synthetic TM peptides revealed that a point mutation of
      one of the residues of the dimerization motif (L75P) located at the N-terminal
      helical turn of the GpA TM fragment, adopts a secondary structure and oligomeric
      state similar to the wild-type sequence in detergents. In addition, both
      glycosylation mapping in biological membranes and molecular dynamics showed that
      the presence of a proline residue at the lipid/water interface has as an effect
      the extension of the helical end. Thus, helix packing can be an important factor
      that determines appearance of proline in TM helices. Membrane proteins might
      accumulate proline residues at the two ends of their TM segments in order to
      modulate the exposition of key amino acid residues at the interface for molecular
      recognition events while allowing stable association and native folding.

PMID- 14672670
TI  - Molecular mechanisms for viral mimicry of a human cytokine: activation of gp130
      by HHV-8 interleukin-6.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV, or HHV-8) encodes a pathogenic
      viral homologue of human interleukin-6 (IL-6). In contrast to human IL-6 (hIL-6),
      viral IL-6 (vIL-6) binds directly to, and activates, the shared human cytokine
      signaling receptor gp130 without the requirement for pre-complexation to a
      specific alpha-receptor. Here, we dissect the biochemical and functional basis of
      vIL-6 mimicry of hIL-6. We find that, in addition to the "alpha-receptor
      independent" tetrameric vIL-6/gp130 complex, the viral cytokine can engage the
      human alpha-receptor (IL-6Ralpha) to form a hexameric vIL-6/IL-6Ralpha/gp130
      complex with enhanced signaling potency. In contrast to the assembly sequence of
      the hIL-6 hexamer, the preformed vIL-6/gp130 tetramer can be decorated with IL
      6Ralpha, post facto, in a "vIL-6-dependent" fashion. A detailed comparison of the
      viral and human cytokine/gp130 interfaces indicates that vIL-6 has evolved a
      unique molecular strategy to interact with gp130, as revealed by an almost
      entirely divergent structural makeup of its receptor binding sites. Viral IL-6
      appears to utilize an elegant combination of both convergent, and unexpectedly
      divergent, molecular strategies to oligomerize gp130 and activate similar
      downstream signaling cascades as its human counterpart.

PMID- 14672671
TI  - A mechanism for polar protein localization in bacteria.
AB  - We investigate a mechanism for the polar localization of proteins in bacteria. We
      focus on the MinCD/DivIVA system regulating division site placement in the rod
      shaped bacterium Bacillus subtilis. Our model relies on a combination of
      geometric effects and reaction-diffusion dynamics to direct proteins to both cell
      poles, where division is then blocked. We discuss similarities and differences
      with related division models in Escherichia coli and also develop extensions of
      the model to asymmetric polar protein localization. We propose that our mechanism
      for polar localization may be employed more widely in bacteria, especially in
      outgrowing spores, which do not possess any pre-existing polar division apparatus
      from prior division events.

PMID- 14672672
TI  - Patient-based measures of outcome in plastic surgery: current approaches and
      future directions.
AB  - OBJECTIVES: To evaluate current approaches to patient-based outcome measurement
      in plastic surgery and make recommendations for future research. METHODS:
      Comprehensive review of the plastic surgery literature relevant to patient-based
      outcomes. RESULTS: Two main types of patient-based outcome measure have been used
      in the plastic surgery literature: generic and disease-specific. The majority of
      studies using generic measures investigate aspects of psychological functioning
      with fewer studies focussing on wider aspects of health-related quality of life.
      Disease-specific measures are mainly used to assess symptoms. However, almost all
      of these are ad-hoc measures produced for a particular study, with no
      psychometric evaluation. CONCLUSIONS: There is a lack of psychometrically sound
      measures, and there is scope for improvement in methodology used in plastic
      surgery research. The development and psychometric testing of new plastic surgery
      specific measures is encouraged.

PMID- 14672673
TI  - Benefits and pitfalls of vertical scar breast reduction.
AB  - A quality assurance study was undertaken three years after beginning the vertical
      scar breast reduction technique. We examined the rate of early and late
      complications (major and minor) and compared these to the formerly used inverted
      T scar and L scar breast reduction techniques. Inverted-T scar breast reductions
      have an early complication rate of up to 20% and a late complication rate of 20
      30%. Our vertical scar breast reduction is a modified Lassus technique,
      incorporating a geometrically based and measurable preoperative marking of the
      breast, a superior pedicle, a central breast resection, an intraoperative
      positioning of the nipple-areola complex, and occasionally a periareolar skin
      resection.In the time span examined (September 1998-December 2001) 153 patients
      could be included in the study. The resection weight per breast ranged from 60 to
      1262 g (mean 390+/-210 g, median 380 g). The early complication rate (hematoma,
      seroma, wound dehiscence, wound infection and necrosis) was 21.6%. Of these
      cases, 19.6% were minor complications. The late complication or imperfection rate
      was evaluated very strictly using the standardized, extended scheme of Ferreira
      (problems of volume, shape, symmetry, areola, scars and position of the breast on
      the thorax) and was 26%. Major late complications necessitating a reoperation
      occurred in 11.1% of cases. These complication rates compare well to those of
      other vertical breast reduction techniques and T scar reductions in our own
      clinic and in the literature. Given that the vertical scar breast reduction
      method also results in shorter scars and a significantly better, long-lasting
      breast projection, this technique is clearly justified to remain the standard
      method at our clinic.

PMID- 14672674
TI  - Breast reconstruction by the free transverse gracilis (TUG) flap.
AB  - The transverse upper gracilis (TUG) flap is a free musculocutaneous (type II)
      flap consisting of a segment of the proximal gracilis muscle and a 25x10 cm skin
      paddle oriented transversely. The vascular pedicle of the TUG flap is the
      ascending branch of the medial circumflex femoral artery with two venae
      comitantes. The pedicle length is 6 cm and the diameter of the artery is 1.6 mm.
      In the year 2002, seven patients had breast reconstruction by the free TUG flap.
      There were three primary and four secondary reconstructions. Five flaps totally
      survived, two flaps were lost (in the same patient).TUG flap is indicated in
      women who seek primary autologous reconstruction after a skin sparing mastectomy,
      have small or moderately large breasts, do not accept scars on the abdomen, back
      or gluteal region, who are large in hips and thighs and want a thigh lift. The
      vascular pedicle although short, permits easy anastomosis of matching vessel
      diameters to the internal mammary vessels. The main possible complication, other
      than thrombosis at the anastomosis, is wound dehiscence on the thigh with
      secondary wound healing. This can happen when the flap is wider than 10 cm.

PMID- 14672675
TI  - The development of the male genitourinary system. I. The origin of the urorectal
      septum and the formation of the perineum.
AB  - The embryological development of the male urinary system remains a subject of
      much controversy. As a result the pathogenesis of congenital anomalies such as
      hypospadias and epispadias, which are presented to the reconstructive surgeon
      remains poorly understood. A review of the literature identifies its three
      principal developmental stages: (1) division of the cloaca into the urogenital
      sinus and hindgut by the urorectal septum and the formation of the perineum; (2)
      the extension of the cloaca and its epithelium in the form of the urethral plate
      through the developing genital tubercle; (3) the separation of this extension
      from the surface during the formation of the urethra. This study, which uses a
      mouse model, examines these developmental stages in detail and together with a
      comprehensive review of the literature resolves many of the controversies
      relating to the development of the male urinary system. It reveals new insights
      into the origin of the associated congenital defects.

PMID- 14672676
TI  - Combination of transconjunctival and endonasal-transantral approach in the repair
      of blowout fractures involving the orbital floor.
AB  - In the repair of orbital blowout fractures through eyelid or conjunctival
      incision, it is difficult to see the posterior edge of the fracture and the
      condition of the herniated tissue before reduction of the orbital contents.
      Prolapsed orbital tissue or infraorbital nerve and vessels may therefore be
      damaged in the reduction. The recently advocated combination of traditional
      transconjunctival approach and endoscopic transantral approach allows reduction
      and reconstruction under clear endoscopic vision without a facial skin incision.
      We modified this technique to make it less invasive and applied it to the repair
      of orbital blowout fractures involving the orbital floor. The use of a 70-degree
      straight endoscope through an enlarged ostium as for functional sinus surgery
      allowed clear sight of the roof of the antrum. During the repair of the orbital
      floor through a transconjunctival approach, reduction and reconstruction was
      assisted from the antrum. Twelve cases of fresh blowout fractures were treated
      with this approach. There were seven male and five female patients. Mean age was
      23.5 years. Causes of injuries were fights, motor vehicle or bicycle accidents,
      and sports. Patients with concomitant fractures involving the orbital rim were
      excluded. Persistent diplopia was present in eight cases and enophthalmos of more
      than 2 mm was detected in five cases preoperatively. The average intervals from
      injury to surgery was 22.8 days.Exploration, reduction and reconstruction of the
      orbital floor fractures were precisely performed with this procedure. Large
      orbital floor defects were reconstructed with silicone sheets, thin iliac bone
      grafts or nasal septal cartilage. In all eight cases that showed diplopia, ocular
      movement recovered and symptomatic diplopia disappeared after surgery.
      Enophthalmos of more than 2 mm was also improved in all five cases. One early
      case showed temporary entropion. Transient numbness of the cheek appeared in five
      cases and temporary maxillary sinusitis recovered in one case. Postoperative
      infection was not observed.This method provides visualisation of posterior edge
      of the fracture and the condition of herniated orbital contents before initiation
      of reduction. Dual manipulation by two surgeons is also possible in reduction and
      reconstruction of the orbital floor.

PMID- 14672677
TI  - An evaluation of the influence of practitioner-led hand clinics on rupture rates
      following primary tendon repair in the hand.
AB  - Practitioner-led hand clinics were introduced in our unit in the year 2000 as a
      response to the high and increasing number of postoperative hand trauma patients
      coming to consultant clinics. The aim of this study was to evaluate the influence
      of these clinics on rupture rates following primary tendon repair in the hand.
      The study specifically examined:zone II flexor tendon repairsflexor pollicis
      longus (FPL) tendon repairsextensor pollicis longus (EPL) tendon repairs.
      Prospective data collection were undertaken for these particular operations over
      a 17-month study period. Prior to the introduction of the practitioner-led hand
      clinics previous audits had demonstrated rupture rates of 30% zone II flexor
      tendon repairs, 16% for FPL repairs and 5% for EPL repairs. Rupture rates after
      the introduction of practitioner-led hand clinics fell in all of the study
      categories-to 17% for zone II flexor tendon repairs, 4% for FPL repairs and 0%
      for EPL repairs. It is suggested that improved continuity of care by experienced
      hand therapists may have contributed to the observed improvements in outcome.

PMID- 14672678
TI  - Primary use of the index finger for reconstruction of amputated thumbs.
AB  - Seven cases of primary reconstruction of traumatic amputation of the thumb using
      the index finger are reported. In six cases, the reconstruction was done using an
      injured index finger, while in one case where the amputation of the thumb was
      through the carpometacarpal joint, an intact index finger was primarily
      pollicised. This reduces cost of treatment, hospitalisation period and allows
      earlier rehabilitation without a period of a 'no thumb experience'. We have
      followed all the patients for a minimum period of 2 years and all of them have
      excellent functional results. We believe that pollicisation of a normal index
      finger, if thumb amputation is through the carpometacarpal joint or an injured
      index finger at the time of initial management of a severely traumatised hand
      with thumb amputation is an excellent technique for thumb reconstruction.

PMID- 14672679
TI  - Reverse dorsal digital and intercommissural flaps used for digital
      reconstruction.
AB  - Reverse dorsal digital and intercommissural flaps offer a simple and versatile
      option for skin cover of distal finger defects, especially when other local flaps
      are not available. Twenty-one reverse dorsal digital flaps were used, on an
      outpatient basis, to cover dorsal soft tissue defects over or beyond the PIP
      joint. All the flaps were transposed as reverse island flaps. The average size of
      the defects was 2.5 cm(2) and they were all used to cover exposed tendon, bone,
      joint or a combination. Twenty flaps survived completely and did not present any
      feature of circulatory difficulty. Marginal necrosis of one flap was noticed,
      while two patients complained of swollen finger 6 months later. No morbidity was
      reported and the patients maintained good range of motion. Various other types of
      flaps that have been used to reconstruct distal digital skin defects are reviewed
      and compared with the reverse dorsal digital and metacarpal flaps.

PMID- 14672680
TI  - The horn shaped fascio-cutaneous flap usage in cutaneous malignancy of the leg.
AB  - The cover of defects in the leg is a surgical challenge, especially in the
      elderly patient. We report our experience in 24 patients, who underwent excision
      of a cutaneous malignancy and subsequent cover of the defect with a horn shaped
      fascio-cutaneous flap. The patients' average age was 77 with a range of 61-89
      years. The average size of the defect covered was 4x4 cm, with a range from 3x3
      to 8x8 cm. There were no flap losses. Two complications presented following
      discharge from hospital, one required further surgery. These findings indicate
      that this technically simple flap is reliable, with a low complication rate (8%),
      and produces an aesthetic result. It provides an alternative to split skin
      grafting for cutaneous malignancy defects of the leg.

PMID- 14672681
TI  - The gastrocnemius with soleus bi-muscle flap.
AB  - The gastrocnemius muscle flap is often insufficient in volume and arc of rotation
      for coverage of a large soft tissue defect of the knee and the upper third of the
      leg. Therefore we developed a new concept of the flap which combines soleus and
      gastrocnemius muscles, named the 'gastrocnemius with soleus bi-muscle flap'. In
      16 cadavers we studied the location and number of perforators, which penetrate
      the gastrocnemius muscle through the soleus muscle. In all cases perforators were
      found in the distal half of the gastrocnemius muscle. Angiography in one fresh
      cadaver confirmed that the soleus muscle could receive the reversed flow from the
      gastrocnemius muscle perforators. We subsequently treated a patient with exposed
      proximal tibia with this flap. This flap is useful to cover a large soft tissue
      defect of the knee and the upper third of the leg.

PMID- 14672682
TI  - Granular cell tumour of the glans penis.
AB  - Granular cell tumour of the glans penis is a rare finding with only two other
      cases reported. This case highlights the importance of achieving the correct
      diagnosis, as differing excision margins are critical, particularly in this site.

PMID- 14672683
TI  - Chronic leg ulcers in Werner's syndrome.
AB  - We report two siblings suffered from Werner's syndrome, which is a rare premature
      aging disorder caused by genetic mutations. They developed premature aging during
      adolescence with loss and graying of hair, short stature, baldness, atrophic
      skin, thin extremities, flat feet, 'bird' face and cataracts. Multiple chronic
      ulcers were noted over the feet in both patients. Healing was prolonged because
      of atrophic subcutaneous tissue, poor perfusion, impaired fibroblast activity and
      the loss of normal foot architecture. Treatment of the ulcers was challenging, as
      flap options were limited over the lower third of the leg and skin grafting was
      not easy as there was a lack of healthy granulations. However, we have
      successfully closed the ulcers with Integra artificial skin and ultra-thin split
      thickness skin grafting with the scalp as donor site. The main purpose of this
      paper is to alert physicians to this syndrome when treatments are being planned
      for patients with chronic leg ulcers.

PMID- 14672684
TI  - Microvascular reconstruction of a giant encephalocele defect in a 10-week-old
      infant.
AB  - Microvascular reconstruction of a cranial defect in a 10-week-old infant, which
      is the youngest case in the literature, is reported. A latissimus dorsi free
      muscle flap was transferred to cover the defect and a split thickness skin graft
      was placed over the muscle flap. Despite the successful flap transfer in this
      case, microvascular reconstruction in an infant has its own risks and infants
      should be discussed as a separate entity apart from the other pediatric patients.

PMID- 14672685
TI  - Removing adhesive retention dressings.

PMID- 14672686
TI  - Digital pressure test for paronychia.

PMID- 14672687
TI  - Transverse scar reduction mammaplasty.

PMID- 14672688
TI  - Correspondence regarding October 31, 2003, Breakthroughs and Views by K. Brown
      and P.L. Carmichael.

PMID- 14672689
TI  - The enhancement effect of gold nanoparticles as a surface modifier on DNA sensor
      sensitivity.
AB  - The enhancement of a single strain DNA probe linked to the sensor surface is of
      crucial importance in DNA molecule recognition. By means of nanogold modification
      of the sensor surface in addition to the nanogold amplifier, DNA detection
      sensitivity higher than 10(-16)mol/L was obtained in a Quartz Crystal
      microbalance (QCM) system, much higher than the ordinary QCM sensor without
      surface modification by nanogold.

PMID- 14672690
TI  - Crystal structure of trypsin-turkey egg white inhibitor complex.
AB  - Crystal structure of the complex between porcine beta-trypsin and the second
      domain of the Kazal-type ovomucoid turkey egg white trypsin inhibitor (OMTKY2)
      has been determined at 1.9A resolution. A peptide fragment from the first domain
      has been crystallized with the complex. Restrained-refinement of the structure
      led to an R-factor of 0.19 for the 32206 reflections. OMTKY2 exhibits the
      canonical Kazal-type fold with a central alpha-helix and a short two-stranded
      anti-parallel beta-sheet. The carbonyl carbon of the reactive site prefers
      trigonal geometry. The reactive site loop geometry of the inhibitor is
      complementary to the surface and charge of the binding site in beta-trypsin.

PMID- 14672691
TI  - First synthesis of a polysaccharide-supported lignin model compound and study of
      its oxidation promoted by lignin peroxidase.
AB  - Veratrylchitosan, a polysaccharide-supported lignin model compound, has been
      synthesised by covalently attaching 3-(3,4-dimethoxybenzyloxy)propionic acid to
      the polysaccharide chitosan through an amide linkage. When this polymer was used
      as a substrate in the oxidation promoted by lignin peroxidase (LiP), significant
      decomposition of the lignin model resulted in the formation of veratraldehyde.
      The oxidation mechanism involves an initial transfer of one electron from
      chitosan to the active species of LiP (LiP I) followed by C(alpha)-H
      deprotonation of an aromatic cation radical. A benzylic radical is then formed
      which is further oxidised to a benzyl cation. Reaction with water and hydrolysis
      of the hemiacetal then lead to veratraldehyde formation. An increase in the
      yields of the oxidation product is observed in the presence of the mediator 2
      chloro-1,4-dimethoxybenzene, thus indicating that a more efficient degradation
      results from the transfer of an electron from the polymer to the radical cation
      of the mediator.

PMID- 14672692
TI  - The possible role of hydrogen sulfide on the pathogenesis of spontaneous
      hypertension in rats.
AB  - Hydrogen sulfide (H(2)S) is a newly found modulator in vascular system. This work
      showed that gene expression of cystathionine gamma-lyase (CSE), a H(2)S
      generating enzyme, and the activity of CSE in thoracic aorta were suppressed in
      hypertension rats. The plasma level of H(2)S also decreased in those rats.
      Exogenous administration of H(2)S could increase the plasma level of H(2)S and
      enhance the CSE activity of aorta. Exogenous administration of H(2)S also
      attenuated the elevation of pressure and lessened the aorta structural remodeling
      during the development of hypertension. In WKY rats, the gene expression and
      activity of CSE also decreased when the endogenous production of H(2)S was
      deprived by administration of DL-propargylglycine (specific inhibitor of CSE),
      accompanying the elevated pressure and the development of vascular remodeling.
      The results showed that endogenous H(2)S system was involved in both the
      maintenance of basal blood pressure and the development of hypertension.
      Exogenous H(2)S could exert beneficial effect on the pathogenesis of spontaneous
      hypertension.

PMID- 14672693
TI  - Purification of antimicrobial factor from granules of channel catfish peripheral
      blood leucocytes.
AB  - The channel catfish (Ictalurus punctatus) is extensively used in aquaculture in
      the Southeast US and is susceptible to many bacterial infections acquired from
      its pond environment. Research is needed to better understand the defensive
      response and innate immunity of channel catfish against fish pathogens like
      Edwardsiella ictaluri and Aeromonas hydrophila. The main objectives were
      purification and characterization of an innate antimicrobial factor isolated from
      catfish leucocytes that has both bactericidal and antiviral activities. Oxygen
      independent mechanisms of innate immunity for killing microorganisms have not
      been identified in leucocytes of channel catfish. Leucocytes were separated from
      catfish blood, and granule extracts were obtained by homogenization,
      centrifugation, and extraction with 10% acetic acid. The granule extracts were
      further purified by gel filtration chromatography. Bactericidal assays against
      the two fish pathogens and SDS-PAGE analysis were done on the isolated
      antimicrobial factor. Determination of antiviral activity of the factor was done
      by in vitro tissue culture using herpes simplex virus-type 1. Mass spectrometry
      analyses were done for molecular weight (655 Da), purity, and structural
      characterization of the innate non-peptide antimicrobial factor.

PMID- 14672694
TI  - A homodimeric laccase with unique characteristics from the yellow mushroom
      Cantharellus cibarius.
AB  - The aim of the present study was to isolate a laccase from fruiting bodies of the
      yellow mushroom Cantharellus cibarius. The fruiting body extract was subjected to
      a purification protocol that involved ion exchange chromatography on DEAE
      cellulose, affinity chromatography on Affi-gel blue gel and Con A-Sepharose, and
      gel filtration by fast protein liquid chromatography on Superdex 75. The laccase
      was unadsorbed on DEAE-cellulose and Affi-gel blue gel and adsorbed on Con A
      Sepharose. The laccase was composed of two identical subunits each with a
      molecular mass of 46 kDa. The laccase exhibited a temperature-dependent rise in
      activity over the temperature range 20-50 degrees C. When the temperature was
      raised above 60 degrees C there was a fall in enzyme activity. The enzyme
      manifested maximal activity at pH 4. At and above pH 6 there was a dramatic
      reduction in activity. The unique features of this fruiting body laccase compared
      with previously reported mycelial laccases include homodimeric nature, a
      distinctive N-terminal sequence, a higher optimal pH, and adsorption on only ConA
      Sepharose among the various chromatographic media tested.

PMID- 14672695
TI  - Specific inhibition of hepatitis C virus replication by cyclosporin A.
AB  - The difficulty in eradicating hepatitis C virus (HCV) infection is attributable
      to the limited treatment options against the virus. Recently, cyclosporin A
      (CsA), a widely used immunosuppressive drug, has been reported to be effective
      against HCV infection [J. Gastroenterol. 38 (2003) 567], although little is
      understood about the mechanism of its action against HCV. In this study, we
      investigated the anti-viral effects of CsA using an HCV replicon system. Human
      hepatoma Huh7 cells were transfected with an HCV replicon expressing a chimeric
      gene encoding a luciferase reporter and neomycin phosphotransferase (Huh7/Rep
      Feo). Treatment of the Huh7/Rep-Feo cells with CsA resulted in suppression of the
      replication of the HCV replicon in a dose-dependent manner, with an IC50 of
      approximately 0.5 microg/ml. There were no changes in the rate of cell growth or
      viability, suggesting that the effect of CsA against HCV is specific and not due
      to cytotoxicity. In contrast, FK506, another immunosuppressive drug, did not
      suppress HCV replication. CsA did not activate interferon-stimulated gene
      responses, suggesting that its action is independent of that of interferon. In
      conclusion, CsA inhibits HCV replication in vitro specifically at clinical
      concentrations. Further defining its mode of action against HCV replication
      potentially may be important for identifying novel molecular targets to treat HCV
      infection.

PMID- 14672696
TI  - A novel LIM and SH3 protein (lasp-2) highly expressing in chicken brain.
AB  - From eluates of F-actin affinity chromatography of chicken brain, we identified a
      novel actin-binding protein (lasp-2) whose gene was predicted in silico. We
      cloned cDNA of chicken lasp-2 and analyzed its structure, expression, activity,
      and localization with lasp-1 (LIM and SH3 protein 1), a previously identified
      actin-binding protein closely related to lasp-2. Chicken lasp-2 showed high
      homology to mammalian putative lasp-2. Both chicken lasp-1 and chicken lasp-2
      have N-terminal LIM domains, C-terminal SH3 domains, and internal nebulin
      repeats. However, lasp-2 is greatly different from lasp-1 in the sequence between
      the second nebulin repeat and a SH3 domain, and the region is conserved in
      chicken, mouse, and human. As expected from its structural similarity to lasp-1,
      lasp-2 possessed actin-binding activity and localized with actin filament in
      filopodia of neuroblastoma. In contrast to lasp-1, which is widely distributed in
      non-muscle tissues, lasp-2 was highly expressed in brain.

PMID- 14672697
TI  - Anti-HIV-1 activity and mode of action of mirror image oligodeoxynucleotide
      analogue of Zintevir.
AB  - Zintevir is an oligonucleotide analogue, which has the phosphorothioate
      modification at both termini, that forms a K(+)-induced quadruplex structure and
      shows potent anti-human immunodeficiency virus (HIV)-1 activity. We synthesized
      the non-modified analogue (D-17mer) of Zintevir and its enantiomer (L-17mer), and
      compared their anti-HIV-1 activity and molecular mechanism of action. Although L
      17mer forms the exact mirror image quadruplex structure of D-17mer, which has a
      very similar structure with Zintevir, L-17mer showed comparable anti-HIV-1
      activity with Zintevir. The results obtained by the time-of-addition experiments
      and the immunofluorescence binding assay strongly suggest that the primary
      molecular target of L-17mer is the viral gp120 envelope protein as well as
      Zintevir, regardless of their reciprocal chirality.

PMID- 14672698
TI  - Peripheral benzodiazepine receptors in potatoes (Solanum tuberosum).
AB  - The peripheral benzodiazepine receptor (PBR), an internal protein of the
      mammalian mitochondrial membrane, is involved in several metabolic functions such
      as steroidogenesis, oxidative phosphorylation, and regulation of cell
      proliferation. Here we report the presence of PBRs in parenchymal and
      meristematic tissues of potato (Solanum tuberosum). PBRs are heterogeneously
      distributed in potato and are highly expressed in meristematic cells. In
      particular the receptor protein is mainly localised in the meristematic nuclear
      subcellular preparation. This 30-36 kDa protein, which corresponds to PBR, is
      increased, indeed, in meristematic compared to the parenchymal tissue. This
      suggests an involvement of this receptor in the regulation of cell plant growth.
      In addition, the demonstration that PBRs are also present in vegetables supports
      the hypothesis of a highly conserved receptor system during phylogenesis.

PMID- 14672699
TI  - Acidic pH enhances structure and structural stability of the capsid protein of
      hepatitis E virus.
AB  - Hepatitis E virus (HEV) is enterically transmitted and endemic to tropical areas
      of the world. The major capsid protein of HEV is pORF2 ( approximately 74 kDa),
      encoded by open reading frame 2 (ORF2). When expressed in insect cells, it is
      processed into a approximately 55 kDa form (n-pORF2). We also generated a mutant,
      m-pORF2, lacking a C-terminal hydrophobic region shown earlier to be required for
      its homo-oligomerization. Circular dichroism was used to measure the secondary
      structure and stability of these proteins as a function of pH and temperature.
      With decreasing pH both proteins acquired increasing alpha-helicity and thermal
      stability in terms of midpoint of denaturation and the Gibbs energy change.

PMID- 14672700
TI  - Identification, structural determination, and biological activity of bovine and
      canine calcitonin receptor-stimulating peptides.
AB  - We have recently identified in porcine brain a series of new peptides, designated
      calcitonin receptor-stimulating peptide-1 (CRSP-1), CRSP-2, and CRSP-3, but
      failed to find their counterparts in humans and rodents by either database
      searching or experimental cross-hybridization. In this study, we isolated cDNAs
      encoding precursors of bovine CRSP-1, canine CRSP-1, and canine CRSP-2 from their
      thyroid cDNA libraries. Although the deduced mature amino acid sequences of
      bovine and canine CRSP-1s and canine CRSP-2 showed identity with their respective
      porcine CRSP counterparts, none of them had a C-terminal amide structure. In LLC
      PK(1) cells endogenously expressing the calcitonin (CT) receptor, bovine and
      canine CRSP-1s enhanced the cAMP production, while canine CRSP-2 did not
      stimulate it at all. Equine CGRP-I had a high identity in its amino acid sequence
      with porcine CRSP-1 and stimulated LLC-PK(1) cells at a potency comparable to
      that of porcine CT. None of these CRSPs or equine CGRP-I stimulated the CT-like
      receptor, even in the presence of receptor activity-modifying proteins. These
      results demonstrate that CRSP-1, a new class of biologically active peptide, is
      present in animals evolutionarily close to pigs and induces its activity through
      the calcitonin receptor, suggesting a wide existence and common properties of
      this peptide in mammals.

PMID- 14672701
TI  - EphB4 signaling is capable of mediating ephrinB2-induced inhibition of cell
      migration.
AB  - Signaling between the ligand ephrinB2 and the respective receptors of the EphB
      class is known to play a vital role during vascular morphogenesis and
      angiogenesis. The relative contribution of each EphB receptor type present on
      endothelial cells to these processes remains to be determined. It has been shown
      that ephrinB2-EphB receptor signal transduction leads to a repulsive migratory
      behavior of endothelial cells. It remained unclear whether this anti-migratory
      effect can be mediated by EphB4 signaling alone or whether other EphB receptors
      are necessary. It also remained unclear whether the kinase activity of EphB4 is
      pivotal to its action. To answer these questions, we developed a cellular
      migration system solely dependent on ephrinB2-EphB4 signaling. Using this system,
      we could show that EphB4 activation leads to the inhibition of cell migration.
      Furthermore we identified PP2, a known inhibitor of kinases of the Src family,
      and PD 153035, a known inhibitor of EGF receptor kinase, as inhibitors of EphB4
      kinase activity. Using PP2, the inhibition of cell migration by ephrinB2 could be
      relieved, demonstrating that the kinase function of EphB4 is of prominent
      importance in this process. These results show that EphB4 activation is not only
      accompanying ephrinB2 induced repulsive behavior of cells, but is capable of
      directly mediating this effect.

PMID- 14672702
TI  - Codon optimization reveals critical factors for high level expression of two rare
      codon genes in Escherichia coli: RNA stability and secondary structure but not
      tRNA abundance.
AB  - Expression patterns in Escherichia coli of two small archaeal proteins with a
      natural content of about 30% rare codons were analyzed. The proteins, a histone
      like protein from Sulfolobus shibatae (Ssh10), and a glutaredoxin-like protein
      from Methanobacterium thermoautotrophicum (mtGrx), were produced with expression
      plasmids encoding wild-type genes, codon-optimized synthetic, and GST-fusion
      genes. These constructs were expressed in BL21 (DE3), its LysS derivative, and
      modified strains carrying copies for rare codon tRNAs or deletions in the RNAseE
      gene. Both Ssh10 and mtGrx expression levels were constitutively high in
      BL21(DE3) and its derivatives, with the exception of the LysS phenotype, which
      prevented high level expression of the Ssh10 wild-type gene. Surprisingly, a
      codon-optimized mtGrx gene construct displayed undetectable levels of protein
      production. The translational block observed with the synthetic mtGrx gene could
      be circumvented by using a synthetic mtGrx-glutathione S-transferase (GST) fusion
      construct or by in vitro translation. Taken together, the results underscore the
      importance of mRNA levels and RNA stability, but not necessarily tRNA abundance
      for efficient heterologous protein production in E. coli.

PMID- 14672703
TI  - Purification and identification of a protein kinase activity modulated by
      ionizing radiation.
AB  - In order to identify novel protein kinases, which are involved in signal
      transduction processes after exposure of cells to ionizing radiation we screened
      HL-60 cells using an in-gel renaturation assay. Using this approach we identified
      a renaturable serine/threonine kinase with an apparent molecular mass of 90 kDa
      (pK90). The activity of pK90 dropped within minutes after exposure to a dose of
      10 Gy. It reached a minimum 15-30 min after irradiation and increased back to pre
      treatment values 6h later. A down-regulation of the kinase activity was
      detectable after a dose of 1 Gy. Failure of H(2)O(2) to down-regulate pK90
      activity indicates a requirement for DNA double-strand-breaks to modulate the
      kinase activity. In contrast to the molecular mass of 90 kDa in SDS-PAGE we found
      a molecular mass of around 450 kDa for the native protein using gel filtration
      chromatography, indicating that pK90 forms a multi-protein complex under native
      conditions. To identify pK90 we partially purified the protein by three affinity
      chromatography steps (heparin-Sepharose, phosphate metal affinity, and Cibacron
      Blue-F3G-A-Sepharose). Mass spectrometric analysis of the purified 90 kDa
      fraction showed that pK90 is identical to Tlk1, which was verified by
      immunoprecipitation.

PMID- 14672704
TI  - Gene expression in precursor cells of prostate cancer associated with activin by
      combination of subtractive hybridization and microarray technologies.
AB  - Prostatic intraepithelial neoplasia (PIN) is considered the pre-malignant stage
      of prostate carcinoma, but little is known of its initiation and evolution. The
      identification of genes associated with these precursors of prostate cancer may
      elucidate the pathways of the early oncogenesis of this disease. Previously, we
      have reported that activin, a member of the TGFbeta superfamily, acted as an
      inhibitory growth factor in prostate cancer. We used laser capture
      microdissection, mRNA-library amplification (RNA-PCR), subtractive hybridization,
      and complementary DNA microarray to examine gene expression profiles in activin
      positive PIN, compared with activin-negative PIN. Subtractive hybridization
      showed that 28 genes were differentially expressed (13 and 15 genes were up- and
      down-regulated, respectively). Microarray analysis identified 29 and 56 more
      genes (4 times) up- and down-regulated, respectively, suggesting that DNA
      microarray is a more effective method in screening gene profiles. We have
      validated the known genes identified by both subtractive hybridization and
      microarray technologies, using Northern blot analysis in the mRNA libraries
      generated from cells microdissected from pathological slides. We have
      successfully showed that at least 13 genes are involved in activin-associated
      PIN. The evaluation of candidate genes that emerge from these experiments
      provides a rational approach to investigate those genes significant in evolution
      from PIN to prostate carcinoma.

PMID- 14672705
TI  - General transcriptional repression by polyglutamine disease proteins is not
      directly linked to the presence of inclusion bodies.
AB  - By using direct immunocytochemistry of BrU incorporated to RNA in the nuclei, we
      evaluated the effect of mutant huntingtin and ataxin-1 on general transcription
      in primary cortical and cerebellar neurons. Our quantitative analyses clearly
      showed that these mutant polyglutamine disease proteins repress general
      transcription. In addition, we found that general transcription level was almost
      similar in inclusion body-positive and -negative neurons. The result suggests
      that presence of inclusion body is not essential for repressing general
      transcription in contrast to its reported role for suppressing specific gene
      transcription in the polyglutamine disease pathology.

PMID- 14672706
TI  - A novel autofeedback loop of Dec1 transcription involved in circadian rhythm
      regulation.
AB  - An autofeedback loop associated with transcription of clock gene(s), Per(s), is
      generally accepted as the molecular machinery of circadian rhythm generation, in
      which CLOCK/BMAL act as positive regulators and PER/CRY as negative ones. We show
      here an autofeedback loop of Dec1 encoding a basic helix-loop-helix transcription
      factor: CLOCK/BMAL increased the promoter activity of Dec1, and DEC1 and DEC2 as
      well as PERs and CRYs suppressed the induced expression. Three CACGTG E-boxes are
      responsible for both the activation and the suppression of Dec1 transcription.
      Forced expression of Clock/Bmal increased endogenous Dec1 mRNA level, and
      overexpression of Dec1 resulted in suppression of Dec2, Per2, and Dbp expression.
      The level of Dec1 expression in the heart of Clock/Clock mutant mice was
      continuously low throughout the day. These findings suggest that Dec1 is
      positively regulated by CLOCK/BMAL and is involved in circadian rhythm regulation
      by suppressing CLOCK/BMAL-induced gene expression. The autofeedback loop of Dec1
      may be interlocked with the core feedback loop of Per in some situations.

PMID- 14672707
TI  - Negative regulation of hematopoiesis by the fused in myeloproliferative disorders
      gene product.
AB  - The t(8;13) translocation, found in a rare and aggressive type of stem cell
      myeloproliferative disorder, leads to the generation of a fusion protein between
      the N-terminal gene product of fused in myeloproliferative disorders (FIM)/ZNF198
      and the fibroblast growth factor receptor 1 (FGFR1) kinase domain. The chimeric
      protein was reported to have constitutively activated tyrosine kinase activity.
      However, little is known about a role of FIM in hematopoietic cell regulation.
      Here we show that FIM protein is ubiquitously expressed in mouse embryonic
      tissues but much less in hematopoietic cells. We also show that forced expression
      of FIM inhibits the emergence of hematopoietic cells in the cultured mouse aorta
      gonad-mesonephros (AGM) region on embryonic day (E) 11.5, where definitive
      hematopoiesis is first found during embryogenesis. These results suggest that the
      expression level of FIM determines the development of hematopoiesis during mouse
      ontogeny.

PMID- 14672708
TI  - Escherichia coli tRNA(4)(Arg)(UCU) induces a constrained conformation of the
      crucial Omega-loop of arginyl-tRNA synthetase.
AB  - Previous investigations show that tRNA(Arg)-induced conformational changes of
      arginyl-tRNA synthetase (ArgRS) Omega-loop region (Escherichia coli (E. coli),
      Ala451-Ala457) may contribute to the productive conformation of the enzyme
      catalytic core, and E. coli tRNA(2)(Arg)(ICG)-bound and -free conformations of
      the Omega-loop exchange at an intermediate rate on NMR timescale. Herein, we
      report that E. coli ArgRS catalyzes tRNA(2)(Arg)(ICG) and tRNA(4)(Arg)(UCU) with
      similar efficiencies. However, 19F NMR spectroscopy of 4-fluorotryptophan-labeled
      E. coli ArgRS reveals that the tRNA(4)(Arg)(UCU)-bound and -free conformations of
      the Omega-loop region interconvert very slowly and the lifetime of bound
      conformation is much longer than 0.33 ms. Therefore, tRNA(4)(Arg)(UCU) differs
      from tRNA(2)(Arg)(ICG) in the conformation-exchanging rate of the Omega-loop.
      Comparative structure model of E. coli ArgRS is presented to rationalize these
      19F NMR data. Our 19F NMR and catalytic assay results suggest that the tRNA(Arg)
      induced conformational changes of Omega-loop little contribute to the productive
      conformation of ArgRS catalytic core.

PMID- 14672709
TI  - Last intron of the chemokine-like factor gene contains a putative promoter for
      the downstream CKLF super family member 1 gene.
AB  - The genes for chemokine-like factor (CKLF) and four chemokine-like factor super
      family members (CKLFSF1-4) are tightly linked on chromosome 16, with only 325 bp
      separating CKLF and CKLFSF1. We used Northern blotting and RT-PCR to show that
      these two genes are expressed independently of one another. We then used a novel
      computational promoter prediction method based on the interaction among
      transcription factor binding sites (TFBSs) to identify a putative promoter region
      for the CKLFSF1 gene. Our method predicted a promoter region in the last intron
      of the upstream gene, CKLF. We PCR amplified the predicted promoter region and
      used a luciferase assay to show that the region was able to drive the luciferase
      gene. DNA decoy experiments indicated that 214 bp fragment neighboring the TATA
      box markedly inhibited CKLFSF1 gene expression. Sequence analysis of the region
      revealed a typical TATA box (TATATAA) and multiple potential transcription factor
      binding sites, providing further evidence for this being a functional promoter
      for CKLFSF1. This work provides the first evidence of a promoter from one gene
      located in an intron of another.

PMID- 14672710
TI  - Involvement of CREB in the transcriptional regulation of the human GM3 synthase
      (hST3Gal V) gene during megakaryocytoid differentiation of human leukemia K562
      cells.
AB  - We studied the transcriptional regulation of human GM3 synthase (hST3Gal V)
      during megakaryocytic differentiation of K562 cells induced by PMA. Northern blot
      and reverse transcription polymerase chain reaction (RT-PCR) indicated that the
      induction of hST3Gal V by phorbol 12-myristate 13-acetate (PMA) is regulated at
      transcriptional level. To elucidate the mechanism underlying the regulation of
      the hST3Gal V gene expression during the differentiation of K562 cells induced by
      PMA, we characterized the promoter region of the hST3Gal V gene. Functional
      analysis of the 5(')-flanking region of the hST3Gal V gene by transient
      expression method showed that the -177 to -83 region, which contains a CREB
      binding site at -143, functions as the PMA-inducible promoter in K562 cells. In
      addition, gel shift assay and site-directed mutagenesis indicated that the CREB
      binding site at -143 is crucial for the PMA-induced expression of the hST3Gal V
      in K562 cells.

PMID- 14672711
TI  - Epigallocatechin-3-gallate, constituent of green tea, suppresses the LPS-induced
      phenotypic and functional maturation of murine dendritic cells through inhibition
      of mitogen-activated protein kinases and NF-kappaB.
AB  - The effects of epigallocatechin-3-gallate (EGCG) on dendritic cells (DC)
      maturation were investigated. EGCG, in a dose-dependent manner, profoundly
      inhibited CD80, CD86, and MHC class I and II expression on bone marrow-derived
      murine myeloid DC. EGCG restored the decreased dextran-FITC uptake and inhibited
      enhanced IL-12 production by LPS-treated DC. EGCG-treated DC were poor
      stimulators of nai;ve allogeneic T-cell proliferation and reduced levels of IL-2
      production in responding T cells. EGCG-pretreated DC inhibited LPS-induced MAPKs,
      such as ERK1/2, p38, JNK, and NF-kappaB p65 translocation. Therefore, the
      molecular mechanisms by which EGCG antagonized LPS-induced DC maturation appeared
      to involve the inhibition of MAPK and NF-kappaB activation. These novel findings
      provide new insight into the immunopharmacological role of EGCG and suggest a
      novel approach to the manipulation of DC for therapeutic application of
      autoimmune and allergic diseases.

PMID- 14672712
TI  - Changes underlying arrhythmia in the transgenic heart overexpressing Refsum
      disease gene-associated protein.
AB  - Previously, we identified a novel neuron-specific protein (PAHX-AP1) that binds
      to Refsum disease gene product (PAHX), and we developed transgenic (TG) mice that
      overexpress heart-targeted PAHX-AP1. These mice have atrial tachycardia and
      increased susceptibility to aconitine-induced arrhythmia. This study was
      undertaken to elucidate the possible changes in ion channels underlying the
      susceptibility to arrhythmia in these mice. RT-PCR analyses revealed that the
      cardiac expression of adrenergic beta(1)-receptor (ADRB1) was markedly lower,
      whereas voltage-gated potassium channel expression (Kv2.1) was higher in PAHX-AP1
      TG mice compared with non-TG mice. However, the expression of voltage-sensitive
      sodium and calcium channels, and muscarinic receptor was not significantly
      different. Propranolol pretreatment, a non-specific beta-adrenoceptor antagonist,
      blocked aconitine-induced arrhythmia in non-TG mice, but not in PAHX-AP1 TG mice.
      Our results indicate that, in the PAHX-AP1 TG heart, the modulation of voltage
      gated potassium channel and ADRB1 expression seem to be important in the
      electrophysiological changes associated with altered ion channel functions, but
      ADRB1 is not involved in the greater susceptibility to aconitine-induced
      arrhythmia.

PMID- 14672713
TI  - Functional expression and characterization of four novel neurotoxins from sea
      anemone Anthopleura sp.
AB  - The genes of four novel neurotoxins, named Hk2a, Hk7a, Hk8a, and Hk16a, were
      obtained from sea anemone Anthopleura sp. All four neurotoxins were composed of
      47 amino acid residues and the variable residues among them were found in
      positions 14, 22, 25, and 37. To study their activities, the four toxins fused to
      the Escherichia coli thioredoxin were overexpressed by BL21 (DE3), cleaved off
      from the fusion partner, purified, and characterized with MALDI-TOF and CD
      assays. Contractile force studies of isolated SD atria indicated that rHk2a had
      the strongest and rHk7a the longest heart stimulation effect. Consequently, the
      Arg14, a highly conserved residue in various sea anemone neurotoxins, can be
      inferred to contribute to the duration but not the intensity of contraction
      stimulating activity. Our work renders useful information to studies of sea
      anemone neurotoxins, especially to the clarification of the function of the
      disputative Arg14.

PMID- 14672714
TI  - Costunolide inhibits interleukin-1beta expression by down-regulation of AP-1 and
      MAPK activity in LPS-stimulated RAW 264.7 cells.
AB  - Costunolide, a sesquiterpene lactone isolated from the root of Saussurea lappa
      Clarke, is known to have a variety of biological activities, including anti
      carcinogenic and anti-fungal activities. Here, we demonstrated the inhibitory
      effect of costunolide on the protein and mRNA expression of interleukin-1beta (IL
      1beta) in LPS-stimulated RAW 264.7 cells. We also showed that costunolide
      suppressed the transcriptional activity of the IL-1beta promoter. Moreover,
      costunolide inhibited the activity of AP-1 transcription factor, and the
      phosphorylation of MAPKs, including SAPK/JNK and p38 MAP kinase. The inhibitory
      effect of costunolide on AP-1 activity was also confirmed by an electrophoretic
      mobility shift assay. Additionally, specific inhibitors of SAPK/JNK and p38 MAP
      kinase, SP600125 and SB203580, also suppressed LPS-induced increase in IL-1beta
      gene expression and AP-1 DNA binding. Taken together, these results demonstrate
      that costunolide inhibits IL-1beta gene expression by blocking the activation of
      MAPKs and DNA binding of AP-1 in LPS-stimulated RAW 264.7 cells.

PMID- 14672715
TI  - Identification and functional analysis of a caveolin-3 mutation associated with
      familial hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are caused by
      mutations in 14 and 15 different disease genes, respectively, in a part of the
      patients and the disease genes for cardiomyopathy overlap in part with that for
      limb-girdle muscular dystrophy (LGMD). In this study, we examined an LGMD gene
      encoding caveolin-3 (CAV3) for mutation in the patients with HCM or DCM. A
      Thr63Ser mutation was identified in a sibling case of HCM. Because the mutation
      was found at the residue that is involved in the LGMD-causing mutations, we
      investigate the functional change due to the Thr63Ser mutation as compared with
      the LGMD mutations by examining the distribution of GFP-tagged CAV3 proteins. It
      was observed that the Thr63Ser mutation reduced the cell surface expression of
      caveolin-3, albeit the change was mild as compared with the LGMD mutations. These
      observations suggest that HCM is a clinical spectrum of CAV3 mutations.

PMID- 14672716
TI  - Heat shock protein 72 binds and protects dihydrofolate reductase against
      oxidative injury.
AB  - Although heat shock protein Hsp72 confers resistance to oxidative injury, the
      mechanisms are unknown. These studies demonstrate that Hsp72 protects
      dihydrofolate reductase (DHFR) against injury caused by the thiol oxidant
      monochloramine (NH(2)Cl). When exposed to NH(2)Cl, DHFR catalytic activity is
      impaired and SDS-PAGE migration retarded. These may be blocked by prior addition
      of Hsp72 or the folate analog methotrexate. Methotrexate binding to DHFR is
      diminished by oxidant treatment, preventable by prior Hsp72 incubation. Hsp72
      also protects DHFR in IEC-18 cells following oxidant exposure. Hsp72 co
      immunoprecipitates with DHFR, especially after partial oxidation. The DHFR-Hsp72
      interaction is modulated by cofactor/substrate binding for both Hsp72 (ATP) and
      DHFR (methotrexate). Thiol oxidation of DHFR increases susceptibility for tryptic
      proteolysis. Preincubation of DHFR with Hsp72 prevents the NH(2)Cl-induced
      sensitivity to proteolysis. Thus, Hsp72 binds DHFR through enhanced protein
      chaperone interactions upon oxidant exposure, a process that may protect against
      irreversible modification of DHFR catalytic and structural integrity.

PMID- 14672717
TI  - Complestatin prevents apoptotic cell death: inhibition of a mitochondrial caspase
      pathway through AKT/PKB activation.
AB  - Complestatin, a bicyclo hexapeptide from Streptomyces, was isolated as a possible
      regulator of neuronal cell death. In this study, we report an anti-apoptotic
      activity of complestatin and its underlying molecular mechanism. Complestatin
      blocked TRAIL (TNF-related apoptosis-inducing ligand)-induced apoptosis and
      activation of caspase-3 and -8 at micromolar concentration levels without
      inhibiting the catalytic activities of these caspases. Complestatin potently
      induced a rapid and sustained AKT/PKB activation and Bad phosphorylation,
      resulting in inhibition of mitochondrial cytochrome c release. These anti
      apoptotic activities of complestatin were significantly abrogated in cells
      expressing dominant negative AKT/PKB. Taken together, our results suggest that
      complestatin prevents apoptotic cell death via AKT/PKB-dependent inhibition of
      the mitochondrial apoptosis signal pathway. The novel property of complestatin
      may be valuable for developing new pharmaceutical means that will control
      unwanted cell death.

PMID- 14672718
TI  - Defining an N-terminal activation domain of the orphan nuclear receptor Nurr1.
AB  - Nurr1 is an orphan nuclear receptor essential for the development of midbrain
      dopaminergic neurons. Activation of Nurr1 depends on two so-called activation
      functions (AFs) situated in the N- and C-terminal regions, respectively. The
      region important for activation within the C-terminal domain has been shown to
      promote activation in a highly cell-type specific fashion in the absence of added
      exogenous ligands. In contrast, the region in the N-terminal domain (AF1) has
      been much less characterized. Here we mutagenized the N-terminal domain of Nurr1
      to define essential activation regions. The results identified a short core
      activation region localized close to the N-terminus of Nurr1. In addition, cell
      type specific influences by other signaling pathways were analyzed by mutagenesis
      of specific conserved phosphorylation sites. The results indicate that mitogen
      activated protein kinase activity (MAPK) positively influences Nurr1 AF1
      dependent transcriptional activation via a conserved phosphorylation site outside
      the core activation region.

PMID- 14672719
TI  - Detection of von Willebrand factor-cleaving protease (ADAMTS-13) in human
      platelets.
AB  - The hemostatic activity of von Willebrand factor (vWF) is strongly dependent on
      its multimeric structure, with the highest activity in 'unusually large'
      multimers secreted from endothelial cells. The multimeric structure is regulated
      by a plasma protease, vWF-cleaving protease (vWF-CP, or ADAMTS-13). ADAMTS-13
      mRNA is variably expressed in liver and other tissues. Because 15-25% of
      circulating vWF is stored in platelets, the presence and function of ADAMTS-13 in
      platelets are important issues. Here we report ADAMTS-13 expression in human
      platelets. Western blot analysis and flow cytometric analysis on permeabilized
      platelets revealed the presence of ADAMTS-13 protein. Real-time PCR demonstrated
      that ADAMTS-13 mRNA is present in platelets of six healthy volunteers, with
      little quantitative difference. The presence of ADAMTS-13 in platelets may imply
      the functional role of this enzyme in the local regulation of platelet function
      at the site of vascular injury or thrombus formation, and provide a useful tool
      for the analysis of structure and function of this enzyme.

PMID- 14672720
TI  - Implication of pH in the catalytic properties of anthrax lethal factor.
AB  - The anthrax lethal factor (LF) is a Zn(2+)-endopeptidase specific for mitogen
      activated protein kinase kinases (MAPKKs), which are cleaved within their N
      terminal region. Much line of effort was carried out to elucidate the catalytic
      activity of LF for designing the inhibitor and to understand the cellular
      mechanism of its cytotoxicity. Current assay methods to analyze the LF activity
      have been based on a synthetic peptide, consisting of 15-20 residues around being
      cleaved. However, there are accumulating reports that the region distal to
      cleavage site is required for the LF-mediated proteolysis of substrate. In this
      study, we demonstrate the catalytic properties of LF, using the full-length
      native substrate, MEK. We described the catalytic properties of LF focused on the
      effects of the pH alteration, which was encountered during the endocytosis of
      lethal toxin, and of the requirement for metal ions. We present the first
      evidence that additional metal ions are required for the LF catalyzed hydrolysis
      of native substrate, and that the pH alteration causes a significant change of
      catalytic properties of LF.

PMID- 14672721
TI  - Potential use of feebate systems to foster environmentally sound urban waste
      management.
AB  - Waste treatment facilities are often shared among different municipalities as a
      means of managing wastes more efficiently. Usually, management costs are assigned
      to each municipality depending on the size of the population or total amount of
      waste produced, regardless of important environmental aspects such as per capita
      waste generation or achievements in composting or recycling. This paper presents
      a feebate (fee+rebate) system aimed to foster urban waste reduction and recovery.
      The proposal suggests that municipalities achieving better results in their waste
      management performance (from an ecological viewpoint) be recompensated with a
      rebate obtained from a fee charged to those municipalities that are less
      environmentally sound. This is a dynamic and flexible instrument that would
      positively encourage municipalities to reduce waste whilst increasing the
      recycling.

PMID- 14672722
TI  - Emissions from a controlled fire in municipal solid waste bales.
AB  - Environmental and safety aspects of seasonal storage of baled municipal solid
      waste to be used as fuel for energy production (waste fuel), was investigated and
      experiments were carried out on burning of bales. The flammability, combustion
      processes and emissions were studied by simulating, in small-scale, potential
      effects of a possible fire in full-scale bale storage area. Despite the high
      water content and the high density of the bales, after setting fire, the bales
      burned well, even though no risk for self-ignition exists. The following
      parameters of the combustion product were measured continuously: O2, CO2, CO,
      SO2, NO, NO2, NOx, THC, smoke gas rate and the temperature of the smoke. Soot
      particles in the smoke were collected and analysed for Hg, Pb, Cd, As, Ni, Cr,
      Mn, Cu, Co, Sb and V concentrations. The analysis of the moisture content,
      concentrations of Hg, Cd, HCl, HF, HBr, NH3, polyaromatic hydrocarbons (PAH),
      chlorinated and brominated dioxins (PCDD/F and PBrDD/F, respectively) were
      carried out. It was found that the PCDD/F levels (TEQs) varied according to the
      system used: 12.53 ng (I-TEF-88)/Nm3; 14.09 ng (I-TEF-99)/Nm3; 13.86 ng
      (Eadons)/Nm3. The PAH concentration was 3.04 microg/Nm3. The contents of the
      metals in the smoke (with the exceptions of Pb and Cd with mean values of 1.74
      and 0.36 mg/m3, respectively) were below the limit values established by the
      Swedish Ministry of Environment for emissions from incineration plants [Swedish
      Ministry of Environment, (2002:1060), Forordning 2002:1060 om avfallsforbranning.
      Available from http://www.notisum.se/rnp/SLS/LAG/20021060.HTM]/EU-directive
      [(2000/76/EC), Directive 2000/76/EC, of the European Parliament and of the
      Council of 4 December 2000 on the Incineration of Waste. http://www.Scotland.
      gov.uk/library5/environment/iecda.pdf]. The HCl concentration was 10 times higher
      than the limit value (mean value of 99 mg/m3).

PMID- 14672723
TI  - Changes in constituent equilibrium leaching and pore water characteristics of a
      Portland cement mortar as a result of carbonation.
AB  - Two equilibrium-based characterization protocols were applied to ground samples
      of a cement-based material containing metal oxide powders in both noncarbonated
      and carbonated states. The effects of carbonation were shown through comparison
      of (i) material buffering capacity, (ii) constituent equilibrium as a function of
      leachate pH, and (iii) constituent solubility and release as a function of liquid
      to-solid (LS) ratio. As expected, the material alkalinity was significantly
      neutralized during carbonation. In addition, carbonation of the cement material
      led to the formation of calcium carbonate and a corresponding increase in arsenic
      release across the entire pH range. The solubility as a function of pH for lead
      and copper was lower in the alkaline pH range (pH>9) for carbonated samples
      compared with the parent material. When solubility and release as a function of
      LS ratio was compared, carbonation was observed to decrease calcium solubility,
      sodium and potassium release, and ionic strength. In response to carbonate solid
      formation, chloride and sulfate release as a function of LS ratio was observed to
      increase. Trends in constituent concentration as a function of LS ratio were
      extrapolated to estimate pore water composition at a 0.06 mL/g LS ratio.
      Significant differences were observed upon comparison of estimated pore water
      composition to leachate concentrations extracted at LS ratio of 5 mL/g. These
      differences show that practical laboratory extractions cannot be assumed directly
      representative of pore water concentrations.

PMID- 14672724
TI  - Removal of PCDD/F from flue gases in fixed or moving bed adsorbers.
AB  - Whereas the PCDD/F-abatement in MSWIs is mostly achieved through entrained-phase
      adsorption upon activated carbon, the other thermal processes are more bending
      towards fixed/moving bed adsorption or catalytic destruction. The treatment of
      entrained-phase adsorption has been previously dealt with. The present paper
      focuses upon fixed/moving bed adsorption as abatement alternative. The
      characteristics of granular carbonaceous adsorbents are reviewed and commented
      upon, and stress some advantages of the fixed/moving bed operation. The
      equilibrium adsorption characteristics are expressed in terms of the number of
      active sites of the adsorbent and its saturation capacity. The breakthrough
      calculations for a fixed/moving bed adsorber are based upon these adsorption
      characteristics and expressed in terms of the relevant operating parameters of
      the flue gases to be treated. Although detailed literature data on these
      adsorbers are scarce, application of the design equations predicts meaningful
      results, thus demonstrating the predictive capacity of the design method.

PMID- 14672725
TI  - Pilot scale field test for compostable packaging materials in the City of Kassel,
      Germany.
AB  - Biodegradable (compostable) packaging materials made from biopolymers (BP) are
      introduced into the market to reduce the amounts of conventional packaging
      materials and at the same time be recovered by the municipal organic waste
      collection system. The processing of this organic waste mixed with biopolymers
      has been tested in a commercial treatment facility. The safe use of the compost
      produced from these materials was demonstrated in a full-scale agricultural
      application test.

PMID- 14672726
TI  - Novel and innovative pyrolysis and gasification technologies for energy efficient
      and environmentally sound MSW disposal.
AB  - Within the context of European Union (EU) energy policy and sustainibility in
      waste management, recent EU regulations demand energy efficient and
      environmentally sound disposal methods of Municipal Solid Waste (MSW). Currently,
      landfill with its many drawbacks is the preferred option in the EU and many other
      industrialised countries. Within the waste management hierarchy thermal disposal
      especially incineration is a viable and proven alternative. But, the dominating
      method, mass-burn grate incineration has drawbacks as well particularly hazardous
      emissions and harmful process residues. In recent years, pyrolysis and
      gasification technologies have emerged to address these issues and improve the
      energy output. To keep the many players in the field comprehensively informed and
      up-to-date, novel and innovative technology approaches emphasising European
      developments are reviewed.

PMID- 14672727
TI  - Identification of novel eubacteria from spent mushroom compost (SMC) waste by DNA
      sequence typing: ecological considerations of disposal on agricultural land.
AB  - A small study was undertaken to examine the microbiological characteristics of
      spent mushroom compost (SMC), which is the major waste by-product of the mushroom
      industry and which is regularly disposed off by application to agricultural land.
      The primary aim of this study was to examine SMC for the presence of faecal
      bacterial pathogens, including Campylobacter spp., Salmonella spp. and Listeria
      monocytogenes. Secondly it was desirable to quantify bacterial and fungal
      populations within SMC, and also qualitatively identify the diversity of
      bacterial populations within SMC, through employment of rDNA PCR and direct
      sequencing techniques on the culturable microflora. Conventional microbiological
      analyses of SMC material (n=30) from six commercial operations in both Northern
      Ireland and the Republic of Ireland, failed to detect Salmonella spp, Listeria
      spp. or Campylobacter spp. in any of the SMC material examined. Total aerobic
      plate counts gave a mean count of log10 7.01 colony forming units (cfu) per gram
      SMC material (range: log10 6.53-7.52 cfu/g). Fungal counts gave a mean count of
      log(10) 4.57 cfu per gram SMC material (range: log10 3.93-4.98 cfu/g). From a
      total of greater than 50 colony picks, a total of 12 bacterial morphotypes were
      identified and were further examined by employment of partial 16S rRNA gene
      amplification and sequencing techniques, yielding several genera and species,
      including Bacillus licheniformis, Bacillus subtilis, Klebsiella/Enterobacter sp.
      Microbacterium sp. Paenibacillus lentimorbus, Pseudomonas mevalonii,
      Sphingobacterium multivorum and Stenotrophomonas sp. This is the first
      preliminary report on the microbial diversity of SMC waste and demonstrates the
      presence of several species that have not been previously described in SMC, in
      addition to two potentially novel species within the genera Microbacterium and
      Stenotrophomonas. It is thereby important to examine the ecological microbe
      microbe and plant-microbe interactions that are occurring between the native
      bacterial soil flora and those added annually (theoretically estimated at
      approximately 10(18) cells) through the application of SMC. Such studies would be
      beneficial in helping to ascertain the ecological consequences involved in the
      disposal of SMC waste on agricultural land.

PMID- 14672728
TI  - Tropical agricultural residues and their potential uses in fish feeds: the Costa
      Rican situation.
AB  - In Costa Rica as many other tropical countries, the disposal problem of
      agricultural wastes is widely recognized but efforts to find solutions are not
      equal for different sectors. This study describes the situation of major
      agricultural residues in Costa Rica, identifying the activities with higher
      amounts produced and, the potential use of these residues in fish feeds. In Costa
      Rica, during the 1993-1994 production season, major agricultural sectors (crop
      and livestock) generated a total amount of 3.15-3.25 million MT of residues
      (classified in by-products: used residues and wastes: not used residues). Some
      residues are treated to turn them into valuable items or to diminish their
      polluting effects (e.g., the so-called by-products). About 1.56-1.63 million MT
      of by-products were used for different purposes (e.g. fertilization, animal
      feeding, fuel, substrates in greenhouses). However, the remainder (1.59-1.62
      million MT) was discharged into environment causing pollution. About 1.07-1.2
      million MT wastes came from major crop systems (banana, coffee, sugarcane and oil
      palm) whereas the remainder came from animal production systems (porcine and
      poultry production, slaughtering). These data are further compared to residues
      estimates for the 2001-2002 production season coming from the biggest crops
      activities. Unfortunately, most of the studied wastes contain high levels of
      moisture and low levels of protein, and also contain variable amounts of
      antinutritional factors (e.g., polyphenols, tannins, caffeine), high fibre levels
      and some toxic substances and pesticides. All these reasons may limit the use of
      these agricultural wastes for animal feeding, especially in fish feeds. The
      potential use of the major vegetable and animal residues in fish feeds is
      discussed based on their nutritional composition, on their amount available over
      the year and on their pollution risks. Other constraints to use these wastes in
      fish feeds are the extra costs of drying and, in most cases, of transportation
      from several dispersed locations. It was stated that most interesting wastes are
      rejected green banana and coffee pulp.

PMID- 14672729
TI  - Characteristics of ashes from different locations at the MSW incinerator equipped
      with various air pollution control devices.
AB  - The characteristics of ashes from different locations at a municipal solid waste
      incinerator (MSWI) equipped with a water spray tower (WST) as a cooling system,
      and a spray dryer adsorber (SDA), a bag filter (BF) and a selective catalytic
      reactor (SCR) as air pollution control devices (APCD) was investigated to provide
      the basic data for further treatment of ashes. A commercial MSWI with a capacity
      of 100 tons per day was selected. Ash was sampled from different locations during
      the normal operation of the MSWI and was analyzed to obtain chemical composition,
      basicity, metal contents and leaching behavior of heavy metals. Basicity and pH
      of ash showed a broad range between 0.08-9.07 and 3.5-12.3, respectively. Some
      major inorganics in ash were identified and could affect the basicity. This could
      be one of the factors to determine further treatment means. Partitioning of
      hazardous heavy metals such as Pb, Cu, Cr, Hg and Cd was investigated. Large
      portions of Hg and Cd were emitted from the furnace while over 90% of Pb, Cu and
      Cr remained in bottom ash. However 54% of Hg was captured by WST and 41% by
      SDA/BF and 3.6% was emitted through the stack, while 81.5% of Cd was captured by
      SDA/BF. From the analysis data of various metal contents in ash and leach
      analysis, such capturing of metal was confirmed and some heavy metals found to be
      easily released from ash. Based on the overall characteristics of ash in
      different locations at the MSWI during the investigation, some considerations and
      suggestions for determining the appropriate treatment methods of ash were made as
      conclusions.

PMID- 14672730
TI  - Sanitary aspect of using partially treated landfill leachate as a water source in
      green waste composting.
AB  - Shredded green wastes were composted in windrows, at the Harewood Whin landfill,
      near the city of York, in West Yorkshire, UK. Landfill leachate were added twice
      during the second and fourth week of the process in two piles. One pile was
      turned once every week for eight weeks and the other was turned twice, during the
      same period. Each time approximately, 2 m3 of leachate was added, into each pile.
      The two piles each contained about 45 m3 of shredded green waste. The effect of
      adding leachate on the sanitisation of the green waste during composting, was
      evaluated based on the changes in the levels of faecal coliforms and faecal
      streptococci. The results suggested that using leachate as the moisture source
      had no significant effect (tested with two factors ANOVA test) on the
      sanitisation process when compared with two similar piles, used as the control,
      for which tap water was used for moisture addition. In all four piles
      sanitisation was almost complete and below the acceptable levels. Additionally,
      the results indicated that there was no significant effect on the sanitisation
      process of the turning frequency.

PMID- 14672731
TI  - An overview of nomegestrol acetate selective receptor binding and lack of
      estrogenic action on hormone-dependent cancer cells.
AB  - The specific pharmacological profile of the 19-norprogestin nomegestrol acetate
      (NOMAC) is, at least in part, defined by its pattern of binding affinities to the
      different steroid hormone receptors. In the present study, its affinity to the
      progesterone receptor (PgR), the androgen receptor (AR) and the estrogen receptor
      (ER) was re-evaluated and compared to those obtained for progesterone (P) and
      several progestins. The characteristics of binding to the PgR in rat uterus were
      determined and Ki were found to be roughly similar with 22.8 and 34.3 nM for
      NOMAC and P, respectively. The binding characteristics of 3H-NOMAC were also
      determined and compared to that of 3H-ORG2058 with Kd of 5 and 0.6 nM,
      respectively for rat uterus and 4 and 3 nM, respectively for human T47-D cells.
      Structure-affinity and -activity relationships were studied on a variety of
      compounds related to NOMAC in order to assess its specificity as a progestin. The
      effects of NOMAC on the binding of androgen to the AR were investigated, using
      rat ventral prostate as target model. Contrary to what was observed for MPA, the
      RBA of NOMAC was found to decline with time, showing anti-androgenic rather than
      androgenic potential, a result that was confirmed in vivo. Regarding the ER,
      since none of the progestins were able to compete with estrogen for binding in
      rat uterus as well as in Ishikawa cells, the induction of alkaline phosphatase
      activity (APase) was used as an estrogen-specific response. It confirmed the
      intrinsic estrogenicity of progestins derived from 19-nor-testosterone (19NT),
      norethisterone acetate (NETA), levonorgestrel (LNG) or norgestimate (NGM) and
      others. In contrast, all P and 19-norP derivatives remained inactive. Finally, to
      complete this overview of NOMAC at the sex steroid receptor levels, the lack of
      estrogenic or estrogenic-like activity was checked out in different in vitro
      models. Data from this study have demonstrated that NOMAC is a progestin that has
      greater steroid receptor selectivity compared to MPA or some other synthetic
      progestins. It may provide a better pharmacological profile than those progestins
      currently in use in HRT and OC.

PMID- 14672732
TI  - Progesterone regulation of activating protein-1 transcriptional activity: a
      possible mechanism of progesterone inhibition of endometrial cancer cell growth.
AB  - The uterine endometrium and cancers derived from it are classic models of hormone
      action: estrogen promotes growth and progesterone inhibits proliferation and
      results in differentiation. We have now identified a major pathway through which
      progesterone causes these growth-limiting effects. Ligand-bound progesterone
      receptors modulate the composition and transcriptional activity of members of the
      activating protein-1 (AP-1) family, and in particular, c-Jun. First, a dominant
      negative form of c-Jun inhibits the constitutive growth of Hec50co cells in a
      manner similar to the effects of progesterone through progesterone B receptors.
      Second, progesterone inhibits the transcriptional activity of the AP-1 complex in
      reporter gene assays. Third, the DNA binding of AP-1 and the composition of the
      individual AP-1 factors on DNA is regulated by progesterone on electrophoretic
      mobility shift assays. Fourth, progesterone strongly inhibits total AP-1 as well
      as c-Jun recruitment to the cyclin D1 promoter, but enhances AP-1 occupancy on
      the p53 and p21 promoters, as shown by chromatin immunoprecipitation assays. The
      effects of progesterone on AP-1 DNA binding are confirmed to result in altered
      transcription of these AP-1 target genes by RT-PCR. These studies establish that
      modulation of AP-1 activity is a potential pathway of progesterone-induced growth
      inhibition in endometrial cancer cells.

PMID- 14672733
TI  - 17Beta-hydroxysteroid dehydrogenase type 2: independent prognostic significance
      and evidence of estrogen protection in female patients with colon cancer.
AB  - The mRNA expression of 17beta-hydroxysteroid dehydrogenase (17HSD) types 1 and 2
      enzymes catalyzing opposite reaction of estrogen metabolism was investigated in
      colon cancer. Further, the significance of the 17HSD type 2 enzyme as a possible
      marker of colorectal cancer (CRC) prognosis was studied. In the normal mucosa,
      17HSD type 2 mRNA was predominantly expressed in the surface epithelium and in
      the upper parts of the crypts. In the lamina propria expression was seen in
      endothelial cells and mononuclear phagocytes. In colorectal tumors, 17HSD type 2
      expression was in most cases downregulated. Female patients had significantly
      more cancers with high 17HSD type 2 mRNA expression (n=11/35; 31%) than male
      patients (n=3/39; 8%) (P=0.02). We observed a significant impact of 17HSD type 2
      mRNA expression on survival in female patients with distal colorectal cancer
      (n=24), with an overall cumulative 5-year survival rate of 54% in those with low
      17HSD type 2 mRNA expression. None of the female patients with high 17HSD type 2
      mRNA expression survived (n=11; P=0.0068; log rank 7.32). In male patients, no
      significant association with survival was observed. Our data provide evidence
      suggesting that low 17HSD type 2 mRNA expression is an independent marker of
      favorable prognosis in females with distal colorectal cancer, supporting the
      presence of gender- and location-related differences in the pathogenesis of colon
      cancer.

PMID- 14672734
TI  - Development of novel steroid sulfatase inhibitors. I. Synthesis and biological
      evaluation of biphenyl-4-O-sulfamates.
AB  - Compounds which interfere with steroid sulfatase (STS) are expected as important
      novel therapeutic drugs for postmenopausal breast tumor. Therefore, a number of
      strategies have been adopted to design and synthesize potent, nonestrogenic STS
      inhibitors. We chose biphenyl as a scaffold for STS inhibitors and synthesized
      some biphenyl-4-O-sulfamate derivatives (29-43). Their inhibitory activity on STS
      and estrogenicity were evaluated. Substitution of electron-withdrawing groups
      (e.g., cyano, nitro) at the 2'- or 4'-position of biphenyl-4-O-sulfamate
      remarkably increased STS-inhibitory activity. Especially, 2',4'-dicyanobiphenyl-4
      O-sulfamate (35, TZS-8478) showed very potent STS-inhibitory activity in vitro.
      The administration of TZS-8478 (0.5 mg/kg per day, p.o., for 5 days) completely
      inhibited rat liver and uterine STS similarly to EMATE (1). Furthermore, TZS-8478
      (10 mg/kg per day, p.o., for 5 days) had no stimulative effect on uterine growth
      in ovariectomized rats, and its desulfamoylated compound (20) was little bound to
      the human estrogen receptor alpha. The identification of a potent steroid
      sulfatase inhibitor without estrogenicity, such as TZS-8478, should be of
      considerable value in evaluating the potential of steroid sulfatase inhibition
      for breast tumor therapy.

PMID- 14672735
TI  - The relationship between aromatase in primary breast tumors and response to
      treatment with aromatase inhibitors in advanced disease.
AB  - Aromatase inhibitors are proving to be more effective than tamoxifen for
      postmenopausal patients with breast cancer. Estrogen concentrations in the breast
      are similar in both premenopausal and postmenopausal women, and several fold
      higher than circulating levels in postmenopausal women. In order to investigate
      the importance of intratumoral aromatase in stimulating the proliferation of the
      tumor, we used immunocytochemistry to determine the extent of aromatase
      expression in relationship to the response of the patient to aromatase inhibitor
      treatment. The relationship between positive staining for aromatase in the
      primary tumor and response to treatment with an aromatase inhibitor was
      investigated in a retrospective study of 102 patients with advanced breast
      cancer. Immunohistochemical staining using a monoclonal antibody against
      aromatase was performed on paraffin embedded tumor tissue. Response was evaluated
      using UICC criteria. Nine out of 13 patients with objective response to treatment
      stained positive and 49 of 89 patients with stable or progressive disease stained
      positive. No significant relationship between positive staining and objective
      response to treatment could be found. When patients with 'clinical benefit' (i.e.
      objective response plus prolonged stable disease of at least 6 months) were
      considered, also no relationship could be found. Further analysis of subgroups
      with positive hormone receptors, treatment with newer generation aromatase
      inhibitors, single metastatic site, non-visceral metastases and previous
      treatment only with tamoxifen did not show any relationship. Tumor aromatase
      expression did not correlate with response of patients with advanced breast
      cancer to aromatase inhibitor treatment. Most patients had relapsed from other
      treatments before receiving an aromatase inhibitor. It seems likely that many of
      these patients had tumors that may have progressed to hormone independence at
      this stage of the disease. Research in patients who have received treatment with
      aromatase inhibitors in earlier stages of disease (first line and adjuvant
      treatment) may provide further information on the relationship between tumor
      aromatase, steroid receptors and response to inhibitor treatment.

PMID- 14672736
TI  - Corticosteroid effect on Caco-2 cell lipids depends on cell differentiation.
AB  - Previous studies from our laboratory have indicated that secondary
      hyperaldosteronism affects phospholipids of rat colonic enterocytes. To assess
      whether this represents a direct effect of mineralocorticoids on enterocytes, the
      role of aldosterone and dexamethasone in the regulation of lipid metabolism was
      examined in Caco-2 cells during development of their enterocyte phenotype.
      Differentiation of Caco-2 cells was associated with increased levels of
      triglycerides (TG) and cholesteryl esters (CE), a decreased content of
      cholesterol and phospholipids and changes in individual phospholipid classes. The
      phospholipids of differentiated cells had a higher content of n-6 polyunsaturated
      fatty acids (PUFA) and lower amounts of monounsaturated (MUFA) and saturated
      fatty acids than subconfluent undifferentiated cells. Differentiated cells
      exhibited a higher ability to incorporate [3H]arachidonic acid (AA) into cellular
      phospholipids and a lower ability for incorporation into TG and CE. Incubation of
      subconfluent undifferentiated cells with aldosterone or dexamethasone was without
      effect on the content of lipids, their fatty acids and [3H]AA incorporation. In
      contrast, aldosterone treatment of differentiated cells diminished the content of
      TG, increased the content of phospholipids and modulated their fatty acid
      composition. The percentage of n-6 and n-3 PUFA in phospholipids was increased
      and that of MUFA decreased, whereas no changes in TG were observed. The
      incorporation of [3H]AA into phospholipids was increased and into TG decreased
      and these changes were blocked by spironolactone. Treatment of differentiated
      cells with dexamethasone increased their CE content but no effect was identified
      upon other lipids, their fatty acid composition and on the incorporation of
      [3H]AA. As expected for the involvement of corticosteroid hormones the
      mineralocorticoid and glucocorticoid receptors were identified in Caco-2 cells by
      RT-PCR. The results suggest that aldosterone had a profound influence on lipid
      metabolism in enterocytes and that its effect depends on the stage of
      differentiation. The aldosterone-dependent changes occurring in phospholipids and
      their fatty acid composition may reflect a physiologically important phenomenon
      with long-term consequences for membrane structure and function.

PMID- 14672737
TI  - Characterization and modulation of sex steroid metabolizing activity in normal
      human keratinocytes in primary culture and HaCaT cells.
AB  - Skin, the largest organ of the human body, synthesizes active sex steroids from
      adrenal C19 precursor steroids. Normal human breast epidermal keratinocytes in
      primary culture were used to evaluate the enzymatic activities responsible for
      the formation and degradation of active androgens and estrogens during
      keratinocyte differentiation. Enzymatic activities, including 3beta
      hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase (3beta-HSD), 17beta
      hydroxysteroid dehydrogenase (17beta-HSD), 5alpha-reductase and 3alpha
      hydroxysteroid dehydrogenase (3alpha-HSD) were measured using [3H] steroids as
      substrates. After 10-60 days in culture, no 3beta-HSD activity was detected, but
      all other activities were measured, demonstrating the ability of keratinocytes to
      convert androstenedione (4-DIONE) into the potent androgen dihydrotestosterone
      (DHT). Furthermore, marked changes in enzymatic activity were observed during
      cell differentiation: 17beta-HSD was first detected during the third week of
      culture, the level of activity reaching a peak during the fourth week. This peak
      was followed by a progressive decrease during keratinization. On the other hand,
      5alpha-reductase and 3alpha-HSD activities were first detected during the fourth
      week of culture. The enzymatic activities involved in the formation and
      degradation of sex steroids were also characterized in the immortalized human
      keratinocyte cell line HaCaT. It was then found that HaCaT cells possess a
      pattern of steroid metabolizing enzymes similar to that of human epidermal
      keratinocytes in culture. Since glucocorticoids are known to exert potent
      pharmacological effects on the skin, the effect of dexamethasone (DEX) on cell
      proliferation and enzymatic activities was determined using HaCaT cells. DEX
      causes a 55% decrease in HaCaT cell proliferation (IC50: 10nM) whereas DEX caused
      a three- to five-fold stimulation of oxidative 17beta-HSD activity in intact
      cells in culture (ED50: 30 nM) and this stimulatory effect was competitively
      blocked by the glucocorticoid antagonist RU486. A four-fold increase in type 2
      17beta-HSD mRNA levels was also observed as measured by real-time PCR,
      correlating with the increase in oxidative activity. No effect of DEX on the
      other enzymatic activities (3beta-HSD, 5alpha-reductase, and 3alpha-HSD) was
      observed. Since increased levels of inflammatory cytokines have been detected in
      some skin diseases then these cytokines might play a role in the differentiation
      of keratinocytes. In this regard, we found that interleukin-4 (IL-4) induced the
      expression of 3beta-HSD in HaCaT cells, thus allowing the cells to produce a
      different set of sex steroids from adrenal C19 precursors. The present data thus
      indicate that HaCaT cells are a useful model to further study the regulation of
      the enzymes involved in the metabolism of sex steroids in keratinocytes.

PMID- 14672738
TI  - Profiling transcript levels for steroidogenic enzymes in fetal tissues.
AB  - Cytochrome P450 (CYP) and hydroxysteroid dehydrogenase enzymes are involved in
      the conversion of cholesterol to steroid hormones. These enzymes are primarily
      expressed in the placenta, adrenal and gonads. Interestingly, some of these
      enzyme activities have been demonstrated in non-endocrine tissues, where they may
      be involved in important paracrine and autocrine actions. This is particularly
      the case in the human fetus where steroid precursors circulate at high levels and
      could be metabolized within tissues to produce active steroid hormones. Herein,
      we tested the hypothesis that transcripts for steroidogenic enzymes are expressed
      in fetal tissues other than the classical steroidogenic organs. To test this
      hypothesis, real-time reverse transcription polymerase chain reaction (RT-RTPCR)
      assays were developed that quantify mRNA levels for steroidogenic acute
      regulatory protein (StAR), cholesterol side-chain cleavage (CYP11A), 3beta
      hydroxysteroid dehydrogenase types 1 and 2 (HSD3B1 and HSD3B2), 17alpha
      hydroxylase (CYP17), 21-hydroxylase (CYP21), 11beta-hydroxylase (CYP11B1),
      aldosterone synthase (CYP11B2) and aromatase (CYP19). The use of RT-RTPCR allows
      the specific detection of these transcripts at levels that would not be
      detectable using northern analysis. In addition, this method can detect levels of
      transcript that would not lead to sufficient protein for detection of enzymatic
      activity of protein by western analysis. Thus, this methodology can detect low
      levels of expression that could play a role in regulating intra-tissue
      concentrations of steroid hormone. Total RNAs used for RT-RTPCR analysis were
      isolated from several human fetal tissues, including adrenal, testis, ovary,
      placenta, aorta, brain, liver, kidney, heart, lung, pancreas, prostate, stomach,
      and thymus. Our findings suggest that RT-RTPCR is a powerful tool for the
      examination of steroidogenic enzyme mRNA expressions. Using this approach, we
      have identified and quantified transcript levels of StAR and steroidogenic
      enzymes in several endocrine and non-endocrine fetal tissues. Even though some of
      the mRNA levels measured in these peripheral tissues are extremely lower in
      respect to the steroidogenic tissues, they could be sufficient to produce local
      (i.e. autocrine and paracrine) effects because produced steroids are not diluted
      into the entire circulation. These findings open new perspectives on the role of
      steroid hormones synthesized locally as probable regulatory factors of the
      development of several organ systems.

PMID- 14672739
TI  - Oxidative 3alpha-hydroxysteroid dehydrogenase activity of human type 10 17beta
      hydroxysteroid dehydrogenase.
AB  - In vitro enzyme assays have demonstrated that human type 10 17beta-hydroxysteroid
      dehydrogenase (17beta-HSD10) catalyzes the oxidation of 5alpha-androstane
      3alpha,17beta-diol (adiol), an almost inactive androgen, to dihydrotestosterone
      (DHT) rather than androsterone or androstanedione. To further investigate the
      role of this steroid-metabolizing enzyme in intact cells, we produced stable
      transfectants expressing 17beta-HSD10 or its catalytically inactive Y168F mutant
      in human embryonic kidney (HEK) 293 cells. It was found that DHT levels in HEK
      293 cells expressing 17beta-HSD10, but not its catalytically inactive mutant,
      will dramatically increase if adiol is added to culture media. Moreover, certain
      malignant prostatic epithelial cells have more 17beta-HSD10 than normal controls,
      and can generate DHT, the most potent androgen, from adiol. This event might
      promote prostate cancer growth. Analysis of the 17beta-HSD10 sequence shows that
      this enzyme does not have any ER retention signal or transmembrane segments and
      has not originated by divergence from a retinol dehydrogenase. The data suggest
      that the unique mitochondrial location of this HSD [Eur. J. Biochem. 268 (2001)
      4899] does not prevent it from oxidizing the 3alpha-hydroxyl group of a C19
      sterol in living cells. The experimental results lead to the conclusion that
      mitochondrial 17beta-HSD10 plays a significant part in a non-classical androgen
      synthesis pathway along with microsomal retinol dehydrogenases.

PMID- 14672740
TI  - Induction of NAD(P)H quinone oxidoreductase and glutathione S-transferase
      activities in livers of female August-Copenhagen Irish rats treated chronically
      with estradiol: comparison with the Sprague-Dawley rat.
AB  - Estradiol (E2) has been linked to both, protection against damage associated with
      chronic diseases or exposure to chemicals, and to the incidence of cancer. In its
      protective role, E2 appears to attenuate oxidative stress while as a carcinogen,
      E2 damages macromolecules via formation of reactive catechol metabolites.
      Alterations in the expression of antioxidant and xenobiotic metabolizing enzymes
      upon administration of pharmacological doses of E2 have been previously
      identified, but the effect of chronic exposure to low concentrations of E2 on
      activities of those enzymes in liver is unclear. The August-Copenhagen Irish
      (ACI) rat is more sensitive to estrogen-induced carcinogenesis than the Sprague
      Dawley rat. Accordingly, the effect of treatment of female ACI and Sprague-Dawley
      rats for 6 weeks with E2 on activities of NAD(P)H quinone oxidoreductase 1
      (NQO1), glutathione peroxidase, glutathione S-transferase (GST), phenol
      sulfotransferase (SULT1A1), cytochrome P450 (CYP450) and UDP
      glucuronosyltransferase (UGT) was studied. Basal expression of these enzymes was
      similar in livers from both strains prior to exposure to E2. However, only NQO1
      and GST activity was increased (3- and 2.5-fold, respectively) in liver cytosol
      of ACI rats treated with E2. In contrast, only NQO1 activity was increased
      modestly in livers of Sprague-Dawley rats. Other enzymes were not significantly
      affected in the livers of ACI or Sprague-Dawley rats following chronic treatment
      with E2. The selective induction of NQO1 and GST activity suggests that under
      physiological conditions, E2 may protect against oxidative stress via elevation
      of these antioxidant enzymes. The marked induction of NQO1 and GST in the ACI rat
      indicates a potential for this strain to be used as a model to study the E2
      mediated modulation of these enzymes in tissues that are either sensitive to E2
      carcinogenesis or to its protective effects.

PMID- 14672741
TI  - Mechanisms governing the accumulation of estrogen receptor alpha in MCF-7 breast
      cancer cells treated with hydroxytamoxifen and related antiestrogens.
AB  - This study aimed at a better understanding of estrogen receptor alpha (ER) up
      regulation induced by partial estrogen antagonists. Effect of treatment with
      hydroxytamoxifen (OH-Tam) on ER level in MCF-7 cells was investigated by an
      approach combining ER measurement (enzyme immunoassay) and morphological
      demonstration (immunofluorescence). Furthermore, the influence of drug exposure
      on the rates of ER synthesis and degradation was assessed by determining
      [35S]methionine incorporated into the receptor in different experimental
      conditions (measurement of synthesis or pulse-chase experiments). ER up
      regulation was already induced by a 1-h pulse treatment with OH-Tam, thus a
      continuous exposure was not required. This process appeared reversible (i.e. ER
      accumulation due to OH-Tam rapidly vanished upon subsequent exposure to 17beta
      estradiol (E2) or the pure antiestrogen RU 58668). While OH-Tam did not affect
      the rate of [35S]methionine incorporation into ER, it clearly caused an
      impairment of ER degradation (pulse-chase experiments) indicating that up
      regulation results from a stabilization of the receptor associated with the
      maintenance of its synthesis. Various tamoxifen derivatives, as well as a few
      related partial antiestrogens, were compared on the basis of binding ability and
      propensity to induce ER up regulation. A close relationship was found between
      both properties. Structure-activity analysis revealed that the capacity of these
      compounds to induce ER up regulation is associated with characteristics of their
      aminoalkyle side-chain, similar to those required for antiestrogenicity.

PMID- 14672742
TI  - Acquired commissural fusion of aortic valves in patients with left ventricular
      assist devices.
AB  - BACKGROUND: Left ventricular assist devices (LVADs) currently are used as bridges
      for patients who deteriorate clinically while awaiting cardiac transplantation.
      At the time of transplantation or subsequent death, we can assess the effect of
      long-term device implantation on cardiac structural changes. We have noted, in
      our years of experience, that aortic valve commissures may fuse in patients
      supported by LVADs. These observations may be important in the use of these pumps
      as long-term destination therapy. METHODS: We examined 33 hearts (both explants
      and autopsy specimens) from patients supported either with vented-electric (VE)
      HeartMates (n = 21) or with implantable pneumatic HeartMates (n = 12). We noted
      commissures involved, fusion length (mm), duration of LVAD support, and type of
      LVAD. As controls, we examined 49 explanted hearts from patients with heart
      failure who were not supported by LVADs. RESULTS: We found commissural fusion in
      17 of the 33 hearts. Of those 17 hearts, 4 (23.5%) had 2 commissural fusions, and
      13 (76.5%) had only 1 fusion. Fusion length ranged from 5 mm to 17 mm (mean, 9.9
      mm). The lesion was more common in patients fitted with VE HeartMates (p <
      0.0002). We found small amounts of commissural fusion in 8 of the 49 control
      hearts. CONCLUSIONS: Acquired commissural fusion is common in patients supported
      by LVADs, particularly the VE HeartMate. The lesion also occurs occasionally in
      failing hearts of patients not supported by LVADs. The significance of the lesion
      in patients who require long-term LVAD support either as a bridge to
      transplantation or as destination therapy is unclear.

PMID- 14672743
TI  - Bridge to transplantation with the Jarvik-7 (CardioWest) total artificial heart:
      a single-center 15-year experience.
AB  - BACKGROUND: At our institution, the total artificial heart (TAH) Jarvik-7
      (CardioWest) has been used since 1986 as a bridge to transplantation for the most
      severely ill patients with terminal congestive heart failure. METHODS: Between
      1986 and 2001, 127 patients (108 males, mean age 38 +/- 13) were bridged to
      transplantation with the Jarvik-7 TAH. All were in terminal biventricular failure
      despite high-dose inotropic support. Nine patients had a body surface area (BSA)
      of <1.6 m(2). In Group I patients (78%), the etiology of cardiac failure was
      dilated cardiomyopathy, either idiopathic (n = 60) or ischemic (n = 38). The
      other 29 patients (Group II) had disease of miscellaneous origin. We analyzed our
      experience with regard to 3 time periods: 1986 to 1992 (n = 63); 1993 to 1997 (n
      = 36); and 1998 to 2001 (n = 33). RESULTS: Although Group II patients represented
      30% of indications before 1992, they comprised only 15% during the 2 subsequent
      periods. Duration of support for transplant patients increased dramatically after
      1997, reaching 2 months for the most recent period (5 to 271 days). In Group I,
      the percentage of transplanted patients increased from 43% before 1993 to 55%
      between 1993 and 1997, and reached 74% thereafter. The major cause of death was
      multiorgan failure (67%). The clinical thromboembolic event rate was particularly
      low with no instance of cerebrovascular accident and 2 transient ischemic
      attacks. Total bleeding complication rate was 26%, including 2 deaths related to
      intractable hemorrhage and 2 others related to atrial tamponade. The cumulative
      experience was 3,606 total implant days with only 1 instance of mechanical
      dysfunction. CONCLUSIONS: TAH is a safe and efficient bridge for patients with
      terminal congestive heart failure awaiting cardiac transplantation.

PMID- 14672744
TI  - Non-invasive assessment of myocardial recovery on chronic left ventricular assist
      device: results associated with successful device removal.
AB  - BACKGROUND: Myocardial recovery may occur in patients with heart failure who are
      receiving left ventricular assist-device support, but identification of
      candidates for device removal remains challenging. We hypothesized that on-line
      quantitative echocardiography during trials of decreased device support alone or
      in combination with exercise cardiopulmonary testing can assess cardiac recovery
      to predict successful device removal. METHODS: We studied 18 patients with severe
      heart failure, aged 45 +/- 19 years, who received 234 +/- 169 days of assist
      device support as a bridge to transplantation. We used echocardiographic
      automated border detection from mid-ventricular short-axis images and non
      invasive arterial pressure to measure beat-to-beat responses in 2 to 5 minute
      trials of decreased device flow. We also assessed maximal oxygen consumption in
      14 patients who could exercise. RESULTS: Six patients experienced myocardial
      recovery and underwent successful device removal; 12 remained device dependent.
      With transient, low assist-device flow, patients with device removal had
      increased echocardiographic stroke area of 27% +/- 36% vs -24% +/- 12% (p < 0.05)
      and fractional area change of 51% +/- 13% vs 23% +/- 11% (p < 0.05) in the
      patients who were device dependent. Estimates of pre-load-adjusted maximal power,
      a relatively load-independent index, were 6.7 +/- 2.1 mW/cm(4) in patients with
      successful device removal vs 1.2 +/- 1.2 mW/cm(4) in patients who were device
      dependent (p < 0.005). Maximal oxygen consumption was 17.2 +/- 1.4 ml/kg/min in
      patients with myocardial recovery vs 13.1 +/- 1.9 ml/kg/min in patients who were
      device dependent (p < 0.005) and correlated with pre-load-adjusted maximal power
      (r = 0.89, p < 0.001). Maximal oxygen consumption >16 ml/kg/min, increased stroke
      area, >40% increase in fractional area change, or pre-load-adjusted maximal power
      >4.0 mW/cm(4) with low device flow were associated with successful device removal
      (p < 0.05). CONCLUSIONS: On-line quantitative echocardiography alone or combined
      with exercise cardiopulmonary testing can assess myocardial recovery of patients
      receiving left ventricular assist-device support and has the potential to
      identify patients who are clinical candidates for device removal.

PMID- 14672745
TI  - Evaluation of host stem cell-derived cardiac myocytes in consecutive biopsies in
      long-term cardiac transplant patients.
AB  - BACKGROUND: Bone marrow-derived stem cells are involved in tissue formation in
      transplanted organs. In human renal cell transplants, recipient-specific cells
      have been shown to participate in regeneration of interstitial tissue. In hepatic
      transplants, hepatocytes with a recipient sex chromosome pattern have been
      observed. Recruitment of stem cells in repair and regeneration of cardiac
      myocytes has been demonstrated in experimental ischemia. Recently, cardiac antral
      myocytes of recipient origin have been shown to populate transplanted hearts in
      gender-mismatched transplants. METHODS: Using the fluorescence in situ
      hybridization (FISH) technique we examined serial post-transplant right
      ventricular biopsies and sections of ventricle (at time of autopsy) of 4 gender
      mismatched female-to-male transplanted hearts (graft survival 0.5 to 10 years,
      mean 5.1 years) for Y chromosomes within cardiac myocytes. RESULTS: We detected
      recipient-specific sex chromosomal patterns in single rare cardiac myocytes in 1
      case in a serial biopsy after 7 years of transplant survival. The other serial
      biopsies, as well as the final sections at autopsy, showed no recipient pattern
      chromosomes within the myocytes. In addition, 2 cases demonstrated Y chromosomes
      in the smooth muscle of intracardiac arteries. CONCLUSION: Development of
      recipient marrow-derived stem cells into functional myocytes in the ventricle of
      transplanted hearts is a rare feature. The higher percentage of stem cell
      population in the cardiac atria may be a feature of tissue repair and/or an early
      feature of transplant physiology. Similar to other transplant organs, recipient
      stem cells are involved in tissue neovascularization.

PMID- 14672746
TI  - Short- and long-term outcomes of combined cardiac and renal transplantation with
      allografts from a single donor.
AB  - Coexisting end-stage heart and kidney failure can be treated by combined cardiac
      and renal transplantation. This study reviews the short- and long-term outcomes
      after such a procedure over a 16-year period at a single institution. All
      patients who underwent single-donor simultaneous heart and kidney transplantation
      during the period of March 1986 to April 2002 (including heart retransplantation)
      were included (n = 13). They were listed for combined heart and kidney
      transplantation as they fulfilled our criteria for irreversible end-stage organ
      failure. Retrospective review of patient data from the transplant database,
      patient case notes and post-mortem reports were carried out. The mean (SD)
      recipient age was 45 (12) years and there were 2 females. The mean pre-operative
      creatinine level was 724 (415) micromol/liter with 9 patients (69.2%) on
      continuous ambulatory peritoneal dialysis and 2 patients (15.4%) on hemodialysis
      prior to transplantation. The 30-day mortality rate was 15.4% (2 of 13). For
      surviving patients the mean creatinine level at hospital discharge was 158 (93)
      micromol/liter. The mean number of acute cardiac rejection episodes per 100
      patient-days was significantly lower (p = 0.01) than that for the heart-only
      transplant group (n = 760) during the same period. The median (interquartile
      range) post-operative survival was 1,969 (620 to 3,468) days. The actuarial
      survival rates (95% confidence interval) at 1 and 10 years were 77% (54% to 100%)
      and 67% (40% to 94%), respectively, and were not significantly different from the
      isolated heart transplant population (p = 0.68). Only 1 episode of acute renal
      rejection was diagnosed on clinical grounds, which was treated accordingly. There
      was no renal allograft loss in the long-term survivors. Combined cardiac and
      renal transplantation with allografts from the same donor has acceptable short-
      and long-term outcomes for patients with coexisting end-stage cardiac and renal
      failure. This group of patients may also experience fewer acute rejection
      episodes post-operatively.

PMID- 14672747
TI  - Recipient intramuscular administration of naked plasmid TGF-beta1 attenuates lung
      graft reperfusion injury.
AB  - BACKGROUND: Gene therapy may be an effective strategy for modulating lung graft
      ischemia-reperfusion injury. We investigated whether recipient intramuscular (IM)
      naked plasmid gene transfer of transforming growth factor beta1-active (TGF-beta1
      active) ameliorates lung graft ischemia-reperfusion injury. METHODS: Preliminary
      studies in F344 rats demonstrated that gastrocnemius muscle transfection of TGF
      beta1-active produced muscle and plasma protein expression at 24 and 48 hours
      after transfection. Recipients (n = 8) received IM injection of naked plasmid
      encoding chloramphenicol acetyl transferase (CAT), TGF-beta1-latent or TGF-beta1
      active, respectively, at 24 or at 48 hours before left lung transplantation. We
      did not treat the control group before transplantation (18-hour cold ischemia).
      Donor lungs were flushed with low-potassium dextran-1% glucose and stored for 18
      hours at 4 degrees C. All groups were killed at 24 hours after transplantation.
      Immediately before killing the animals, we clamped the contralateral right hilum
      and assessed graft function. We measured wet-to-dry ratio (W/D), myeloperoxidase,
      pro-inflammatory cytokines (interleukin 1 [IL-1], tumor necrosis factor alpha
      [TNF-alpha], interferon-gamma [INF-gamma], and IL-2) and performed
      immunohistochemistry. RESULTS: Arterial oxygenation was greatest in the recipient
      group transfected with TGF-beta1-active at 24 hours before transplantation
      compared with CAT, TGF-beta1-latent, and 18-hour cold ischemia groups (p < 0.01).
      The W/D ratio and myeloperoxidase decreased in both 24- and 48-hour groups, with
      TGF-beta1-active compared with CAT, and 18-hour cold ischemia groups (W/D, p <
      0.02 and p < 0.004, respectively; myeloperoxidase, p < 0.05 and p < 0.01,
      respectively). All pro-inflammatory cytokines decreased in the 24-hour TGF-beta1
      active group compared with CAT, TGF-beta1-latent, 18-hour and 1-hour cold
      ischemia, and non-treated lung groups (IL-1beta, p < 0.03; TNF-alpha, p < 0.02;
      IFN-gamma, p < 0.001; IL-2, p < 0.0001). In 24- and 48-hour groups with TGF-beta1
      active, immunohistochemistry showed marked staining of Type I and Type II
      alveolar cells and of macrophages from the apical to the caudal sections of the
      lung grafts. CONCLUSIONS: Recipient IM administration of naked plasmid encoding
      TGF-beta1-active before transplantation ameliorates lung isograft reperfusion
      injury after prolonged ischemia.

PMID- 14672748
TI  - Sodium-hydrogen inhibitor cariporide (HOE 642) improves in situ protection of
      hearts from non-heart-beating donors.
AB  - BACKGROUND: Reperfusion injury is a vital problem in non-heart-beating donor
      (NHBD) organs. The sodium-hydrogen inhibitor cariporide is thought to improve
      cellular integrity after ischemia and reperfusion. Recently, we demonstrated the
      possibility of preserving hearts with in situ perfusion after circulatory death.
      The purpose of this study was to determine whether cariporide improves in situ
      heart protection. METHODS: We studied 20 pigs (18 +/- 2 kg). Hearts in the
      conventional group (CON, n = 6) underwent cardioplegic arrest with University of
      Wisconsin solution and then were explanted and stored for 150 minutes on ice. In
      the other groups, a catheter was placed in each ascending aorta and right atrium.
      After disconnecting the ventilator, hypoxia caused circulatory arrest within 7 +/
      2 minutes. The aorta was endoclamped, and continuous in situ perfusion of the
      aortic root was maintained for 60 minutes with University of Wisconsin solution
      (UW, n = 7) or with UW solution and cariporide (CAR, n = 7). After explantation,
      the hearts were stored on ice for 90 minutes. In all groups, hearts were
      reperfused with homologous, whole pig blood in an isolated working heart model
      for 45 minutes. We monitored stroke-work index on-line, intermittently measured
      troponin I and malondialdehyde, and compared light microscopic examinations among
      the groups. RESULTS: Stroke-work index was higher in the CAR group compared with
      the UW group during the last 20 minutes of reperfusion (10(3)dynes x cm x beats(
      1)x gm(-1), 6.6 +/- 1.4 vs 4.5 +/- 2.0, p < 0.05), troponin I was lower in the
      CAR group compared with the UW group (161 +/- 32 ng/ml vs 277 +/- 35 ng/ml, p <
      0.05). Results of malondialdehyde and light microscopic examinations were
      slightly better in the CAR group, without reaching statistical significance.
      CONCLUSION: Cariporide as an additive to UW solution improves functional recovery
      and decreases myocardial damage in hearts from NHBDs protected with an in situ
      perfusion technique.

PMID- 14672749
TI  - In vivo evaluation of the novel calcineurin inhibitor ISATX247 in non-human
      primates.
AB  - BACKGROUND: ISA(TX)247 is a novel calcineurin inhibitor that has shown more
      potency than cyclosporine in vitro. This is the first in vivo study of the
      effects of ISA(TX)247 on lymphocyte functions in non-human primates. METHODS:
      Groups of cynomolgus monkeys were treated orally twice daily for 7 days, each
      dose consisting of 25 mg/kg cyclosporine (n = 5), 25 mg/kg ISA(TX)247 (n = 6) or
      50 mg/kg ISA(TX)247 (n = 6). Levels of cyclosporine and ISA(TX)247 in whole blood
      were measured by liquid chromatography/mass spectrometry. After mitogen
      stimulation, lymphocyte proliferation was assessed by tritium-labeled thymidine
      incorporation and by flow cytometry (expression of proliferating cell nuclear
      antigen in cells in S/G(2)M phase). Flow cytometry was also used to assess
      production of intracellular cytokines by T cells (interleukin-2, interferon
      gamma, tumor necrosis factor-alpha) and expression of T-cell surface activation
      antigens (CD25, CD71, CD11a, CD95, CD154). RESULTS: Trough (C(14 hr)) and peak
      (C(3 hr)) drug levels, as well as area under the concentration-time curve, were
      significantly higher for cyclosporine than ISA(TX)247 (370 ng/ml vs 70 ng/ml, 877
      ng/ml vs 303 ng/ml and 6,262 ng. h/ml vs 1,979 ng. h/ml, respectively). On Day 7
      at C(14 hr), lymphocyte proliferation had been suppressed by approximately 50% in
      all groups compared with proliferation before treatment. Three hours after
      dosing, lymphocyte proliferation was inhibited significantly more by ISA(TX)247
      (approximately 80%, with no differences between the two ISA(TX)247 dose levels)
      than by cyclosporine (65% inhibition). Similar differences between the
      immunosuppressive effects of ISA(TX)247 and cyclosporine were found for
      inhibition of expression of T-cell surface activation antigens. Despite lower
      ISA(TX)247 exposures compared with cyclosporine, the cyclosporine treatment only
      rarely suppressed cytokine production more than treatment with ISA(TX)247.
      CONCLUSIONS: In non-human primates, ISA(TX)247 produces a greater or similar
      inhibition of lymphocyte proliferation, expression of T-cell activation surface
      antigens, and cytokine production when compared with cyclosporine, despite
      ISA(TX)247's lower blood levels and total exposure. We conclude that ISA(TX)247
      suppresses diverse T-cell functions more potently than cyclosporine in non-human
      primates in vivo.

PMID- 14672750
TI  - Early detection of left ventricular dysfunction related to transplant coronary
      artery disease.
AB  - BACKGROUND: Transplant coronary artery disease (TxCAD) is a major limitation to
      the long-term success of cardiac transplantation. We assessed left ventricular
      (LV) function in relation to severity of coronary lesions to improve both early
      diagnosis of TxCAD and evaluation of the severity of myocardial damage. METHODS:
      Echocardiographic evaluation of LV function, including pulsed-wave tissue Doppler
      imaging (PW-TDI) wall motion analysis, was performed in 304 heart recipients
      before each of their follow-up cardiac catheterizations. LV systolic and
      diastolic parameters obtained both invasively and non-invasively were tested for
      their relation to angiographic and intravascular ultrasound (IVUS) findings.
      RESULTS: LV end-diastolic pressure and most of the PW-TDI parameters differed
      significantly (p < 0.001) between patients with and without TxCAD. In comparison
      to patients without the disease, even those with moderate, angiographically non
      visible TxCAD showed significant differences for all systolic PW-TDI parameters.
      Wall motion alterations during angiographic TxCAD were almost always global and
      related mainly to diffuse Type B lesions. Systolic PW-TDI parameter changes
      showed highly predictive values for TxCAD. At systolic wall motion peak velocity
      (Sm) values constantly <10 cm/sec, we found a 97.37% likelihood of TxCAD
      (angiographically and/or IVUS-visible), whereas Sm values of > or =11 cm/sec
      excluded angiographic TxCAD with 90.41% probability. CONCLUSIONS: Among all
      parameters investigated for the evaluation of allograft LV function, PW-TDI
      systolic parameters were of the greatest diagnostic value. Wall motion assessment
      allows early detection of myocardial dysfunction and provides information on both
      local and global LV dysfunction linked to TxCAD, with potential usefulness for
      both timing of cardiac catheterizations and prognostic evaluation.

PMID- 14672751
TI  - Effect of complement fragment 1 esterase inhibition on survival of human decay
      accelerating factor pig lungs perfused with human blood.
AB  - BACKGROUND: The role of complement in hyperacute lung xenograft rejection has not
      been fully elucidated. The present study evaluates the effect of complement (C) 1
      esterase inhibition on hyperacute rejection of human decay-accelerating factor
      (hDAF)-positive pig lung by human blood. METHODS: Using a modification of an
      established ex vivo model, right and left lungs from individual animals were
      surgically isolated and separately perfused. Pigs homozygous for hDAF were
      perfused with fresh human blood that was either untreated or treated with
      complement 1 esterase inhibitor (C1-Inh) at doses of 1 U/ml (n = 5), 5 U/ml (n =
      3) or 10 U/ml plasma (n = 5). RESULTS: Only C1-Inh at 10 U/ml prolonged survival
      time (230 +/- 48.3 minutes) as compared with controls (65.6 +/- 26.5 minutes, p <
      0.05) and diminished complement activation (C3a and C5a, p < 0.05).
      Interestingly, a low concentration of C1-Inh increased the pulmonary vascular
      resistance (PVR; 1 U/ml: 0.54 +/- 0.3; 10 U/ml: 0.19 +/- 0.08). Sequestration of
      neutrophils (92 +/- 3%) and platelets (64 +/- 13%) was not prevented by any
      concentration of C1-Inh. Tissue deposition of C3b and C5b-9 were diminished by
      hDAF expression, and further blunted by treatment, with 10 U/ml C1-Inh.
      CONCLUSIONS: Complement plays a critical role in early events of lung hyperacute
      rejection (HAR). However, even potent inhibition of C1 esterase and C3/C5
      convertase, using serum C1-Inh in pig lungs homozygous for hDAF expression, does
      not prevent rapid lung injury. Our findings implicate innate immune pathways
      resistant to efficient complement regulation, and suggest a role for neutrophils
      and platelets in the lung's particular vulnerability.

PMID- 14672752
TI  - Long-term decrease in subjective perceived efficacy of immunosuppressive
      treatment after heart transplantation.
AB  - BACKGROUND: Mild, long-term non-compliance with immunosuppressive treatment after
      organ transplantation is common, and can result in early mortality. One possible
      source of non-compliance is the belief that the treatment is ineffective or
      unnecessary. This study investigates patients perception of the efficacy of their
      immunosuppressive treatment in a sample of heart transplant patients. METHODS: A
      questionnaire was given to 67 heart transplant recipients. The first part of the
      questionnaire addressed health-related behavior and attitude toward the
      immunosuppressive medication, using self-report questions. In the second part of
      the questionnaire, participants evaluated the perceived risk of rejection
      associated with non-compliant behaviors described in 8 scenarios. RESULTS: The
      data from the self-report questions showed a mild level of behavioral non
      compliance, increasing over time, and a mild level of medication non-compliance.
      One third of the medication non-compliant patients chose the inefficacy or non
      necessity of the treatment as a main cause of non-compliance. The second part of
      the questionnaire showed that subjective perceived efficacy of the
      immunosuppressive treatment decreased over time. CONCLUSIONS: Medication non
      compliance is fostered by many factors. One of these is the belief that the
      treatment is ineffective or unnecessary. This belief increases over time, and
      could be the result of a non-clinical selective-attention bias.

PMID- 14672753
TI  - Herbal bioactivation: the good, the bad and the ugly.
AB  - It has been well established that the formation of reactive metabolites of drugs
      is associated with drug toxicity. Similarly, there are accumulating data
      suggesting the role of the formation of reactive metabolites/intermediates
      through bioactivation in herbal toxicity and carcinogenicity. It has been
      hypothesized that the resultant reactive metabolites following herbal
      bioactivation covalently bind to cellular proteins and DNA, leading to toxicity
      via multiple mechanisms such as direct cytotoxicity, oncogene activation, and
      hypersensitivity reactions. This is exemplified by aristolochic acids present in
      Aristolochia spp, undergoing reduction of the nitro group by hepatic cytochrome
      P450 (CYP1A1/2) or peroxidases in extrahepatic tissues to reactive cyclic
      nitrenium ion. The latter was capable of reacting with DNA and proteins,
      resulting in activation of H-ras oncogene, gene mutation and finally
      carcinogenesis. Other examples are pulegone present in essential oils from many
      mint species; and teucrin A, a diterpenoid found in germander (Teuchrium
      chamaedrys) used as an adjuvant to slimming diets. Extensive pulegone metabolism
      generated p-cresol that was a glutathione depletory, and the furan ring of the
      diterpenoids in germander was oxidized by CYP3A4 to reactive epoxide which reacts
      with proteins such as CYP3A and epoxide hydrolase. On the other hand, some
      herbal/dietary constituents were shown to form reactive intermediates capable of
      irreversibly inhibiting various CYPs. The resultant metabolites lead to CYP
      inactivation by chemical modification of the heme, the apoprotein, or both as a
      result of covalent binding of modified heme to the apoprotein. Some examples
      include bergamottin, a furanocoumarin of grapefruit juice; capsaicin from chili
      peppers; glabridin, an isoflavan from licorice root; isothiocyanates found in all
      cruciferous vegetables; oleuropein rich in olive oil; dially sulfone found in
      garlic; and resveratrol, a constituent of red wine. CYPs have been known to
      metabolize more than 95% therapeutic drugs and activate a number of
      procarcinogens as well. Therefore, mechanism-based inhibition of CYPs may provide
      an explanation for some reported herb-drug interactions and chemopreventive
      activity of herbs. Due to the wide use and easy availability of herbal medicines,
      there is increasing concern about herbal toxicity. The safety and quality of
      herbal medicine should be ensured through greater research, pharmacovigilance,
      greater regulatory control and better communication between patients and health
      professionals.

PMID- 14672754
TI  - Neuroprotective effect of curcumin in middle cerebral artery occlusion induced
      focal cerebral ischemia in rats.
AB  - Free radical induced neuronal damage is implicated in cerebral ischemia
      reperfusion (IR) injury and antioxidants are reported to have neuroprotective
      activity. Several in vitro and in vivo studies have proved the antioxidant
      potential of curcumin and its metabolites. Hence, in the present study the
      neuroprotective potential of curcumin was investigated in middle cerebral artery
      occlusion (MCAO) induced focal cerebral IR injury. 2 h of MCAO and 22 h of
      reperfusion resulted in the infarct volume of 210.39 +/- 31.25 mm3.
      Administration of curcumin 100 and 300 mg/kg, i.p. 30 min. after MCAO produced
      37.23 +/- 5.10% and 46.39 +/- 10.23% (p < 0.05) reduction in infarct volume,
      respectively. Ischemia induced cerebral edema was reduced in a dose dependent
      manner. Curcumin at 300 mg/kg, i.p. produced 50.96 +/- 6.04% reduction in edema
      (p < 0.05) volume. Increase in lipid peroxidation after MCAO in ipsilateral and
      contralateral hemisphere of brain was observed, which was reduced by curcumin
      (300 mg/kg, i.p.)-treatment. Decrease in superoxide dismutase and glutathione
      peroxidase activity was observed in ipsilateral hemisphere of MCAO animal.
      Curcumin-treatment (300 mg/kg, i.p.) prevented IR injury mediated fall in
      glutathione peroxide activity. Peroxynitrite measured using rhodamine123
      fluorescence and anti-nitrotyrosine immunofluorescence indicated increased
      peroxynitrite formation after IR insult. Curcumin-treatment reduced peroxynitrite
      formation and hence the extent of tyrosine nitration in the cytosolic proteins.
      These results suggest the neuroprotective potential of curcumin in cerebral
      ischemia and is mediated through its antioxidant activity.

PMID- 14672755
TI  - Soy protein diet ameliorates renal nitrotyrosine formation and chronic
      nephropathy induced by puromycin aminonucleoside.
AB  - It has been shown that reactive oxygen species are involved in chronic puromycin
      aminonucleoside (PAN) induced nephrotic syndrome (NS) and that a 20% soy protein
      diet reduces renal damage in this experimental model. The purpose of the present
      work was to investigate if a 20% soy protein diet is able to modulate kidney
      nitrotyrosine formation and the activity of renal antioxidant enzymes (catalase,
      glutathione peroxidase, Cu,Zn- or Mn-superoxide dismutase) which could explain,
      at least in part, the protective effect of the soy protein diet in rats with
      chronic NS induced by PAN. Four groups of rats were studied: (1) Control rats fed
      20% casein diet, (2) Nephrotic rats fed 20% casein diet, (3) Control rats fed 20%
      soy protein diet, and (4) Nephrotic rats fed 20% soy protein diet. Chronic NS was
      induced by repeated injections of PAN and rats were sacrificed at week nine. The
      soy protein diet ameliorated proteinuria, hypercholesterolemia, and the increase
      in serum creatinine and blood urea nitrogen observed in nephrotic rats fed 20%
      casein diet. Kidney nitrotyrosine formation increased in nephrotic rats fed 20%
      casein diet and this increase was ameliorated in nephrotic rats fed 20% soy
      protein diet. However, the soy protein diet was unable to modulate the
      antioxidant enzymes activities in control and nephrotic rats fed 20% soy protein
      diet. Food intake was similar in the two diet groups. The protective effect of a
      20% soy protein diet on renal damage in chronic nephropathy induced by PAN was
      associated with the amelioration in the renal nitrotyrosine formation but not
      with the modulation of antioxidant enzymes.

PMID- 14672756
TI  - Behavioral effects of inhibition of cannabinoid metabolism: The amidase inhibitor
      AM374 enhances the suppression of lever pressing produced by exogenously
      administered anandamide.
AB  - Biochemical investigations have identified putative enzymatic pathways for the
      synthesis and metabolism of endogenous cannabinoids. Anandamide amidase is an
      enzyme that metabolizes anandamide into arachadonic acid and ethanolamine. Using
      in vitro methods, various inhibitors of amidase have been identified. The present
      studies were undertaken to determine if the amidase inhibitor AM 374 could
      enhance the effects of intraperitoneal (IP) injections of anandamide. Three
      studies were conducted to investigate the effects of various drug treatments on
      fixed ratio 5 operant lever pressing for food reinforcement. In the first study,
      the effects of different doses of anandamide were assessed, and it was
      demonstrated that 5.0 and 10.0 mg/kg anandamide IP significantly suppressed lever
      pressing, while 2.5 mg/kg produced very little effect. The second study tested
      the effects of intraventricular (ICV) injections of AM 374, and it was observed
      that doses up to 10.0, 20.0 and 40 microg AM 374 had no significant effect upon
      lever pressing. The third study investigated the combined effect of AM374 with a
      low dose of anandamide. Rats received two drug injections: one ICV and one IP.
      Four different drug treatments were assessed: 1) ICV vehicle + IP vehicle, 2) ICV
      vehicle + 2.5 mg/kg anandamide IP, 3) ICV 20.0 microg AM 374 + IP vehicle, and 4)
      ICV 20 microg AM 374 + 2.5 mg/kg anandamide IP. Combined administration of AM 374
      plus anandamide led to a significant decrease in lever pressing compared to
      either AM374 or anandamide administered alone. Observations of the animals
      treated with the combination of AM374 plus anandamide indicated that the drug
      combination resulted in motor slowing, which is consistent with the notion that
      stimulation of cannabinoid receptors produced a motor deficit that interfered
      with lever pressing. Although AM374 produced no effect on its own, this amidase
      inhibitor did enhance the behavioral effect of a low dose of anandamide. These
      results are consistent with the notion that AM 374 inhibited the enzymatic
      breakdown of exogenously injected anandamide. This type of procedure can be used
      to assess a variety of different compounds for their ability to inhibit
      cannabinoid metabolism.

PMID- 14672757
TI  - Antioxidant and anticancer activity of extract from Betula platyphylla var.
      japonica.
AB  - The antioxidant and anticancer properties of a medicinal plant, Betula
      platyphylla var. japonica were investigated. The total methanol extract of B.
      platyphylla var. japonica had protective effects against hydrogen peroxide (H2O2)
      in the Chinese hamster lung fibroblast (V79-4) cell line and induced apoptotic
      cell death in human promyelocytic leukemia (HL-60) cells, a cancer cell line. B.
      platyphylla var. japonica extract significantly increased cell viability against
      H2O2. The extract also showed high 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical
      scavenging activity (IC50 2.4 microg/ml) and lipid peroxidation inhibitory
      activity (IC50 below 4.0 microg/ml). Furthermore, B. platyphylla var. japonica
      extract reduced the number of V79-4 cells arrested in G2/M in response to H2O2
      treatment and increased the activities of several cellular antioxidant enzymes,
      including superoxide dismutase, catalase and glutathione peroxidase. Treatment
      with B. platyphylla var. japonica extract induced cytotoxicity and apoptosis in
      HL-60 cells, as shown by nucleosomal DNA fragmentation, increases in the
      subdiploid cell population, and fluorescence microscopy. B. platyphylla var.
      japonica extract gradually increased the expression of pro-apoptotic Bax and led
      to the activation of caspase-3 and cleavage of PARP. These findings suggest that
      B. platyphylla var. japonica exhibits potential antioxidant and anticancer
      properties.

PMID- 14672758
TI  - Extracts of St. John's wort and various constituents affect beta-adrenergic
      binding in rat frontal cortex.
AB  - The present study was designed to get further insight into the mode of
      antidepressant action of extracts prepared from St. John's wort (SJW) and
      relevant active constituents. Down-regulation of central beta-adrenergic
      receptors (beta-AR's) has been widely considered a common biochemical marker of
      antidepressant efficacy. Although previous studies have reported a beta-AR down
      regulation for SJW extracts, in vivo studies that compare the effects of SJW
      extracts with those of relevant active constituents on beta-AR density have not
      been done yet. We used quantitative radioligand receptor-binding-studies to
      examine in rats the effects of short-term (2 wks) and long-term (8 wks)
      administration of different SJW extracts and constituents on beta-AR binding in
      rat frontal cortex. The effects were compared to those of the standard
      antidepressants imipramine and fluoxetine. [125I]CYP binding to beta-AR was found
      to be decreased after short as well as after long-term treatment with imipramine
      (36%, 40%). Short-term treatment with fluoxetine decreased the number of beta
      adrenergic receptors (17%) while long-term treatment with fluoxetine elicited an
      increase (14%) in beta-AR-binding. This effect was comparable to that of the
      lipophilic CO2 extract which decreased beta-AR-binding (13%) after two weeks and
      slightly increased the number of beta-AR's after 8 weeks (9%). Short-term
      treatment with the methanolic SJW extract decreased beta-AR-binding (14%), no
      effects for this extract were observed after 8 weeks. Treatment with hypericin
      led to a significant down-regulation (13%) of beta-AR's in the frontal cortex
      after 8-weeks, but not after 2 weeks, while hyperforin (used as
      trimethoxybenzoate, TMB), and hyperoside were ineffective in both treatment
      paradigms. Compared to the SJW extracts and single compounds the effect of
      imipramine on beta-AR-binding was more pronounced in both treatment paradigms.

PMID- 14672759
TI  - Characteristic expression of aryl hydrocarbon receptor repressor gene in human
      tissues: organ-specific distribution and variable induction patterns in
      mononuclear cells.
AB  - To investigate the expression of aryl hydrocarbon receptor repressor (AhRR) and
      related molecules in various tissues and the effects of aromatic hydrocarbons
      (AHs) on their expression, we developed a reliable technique of quantification of
      human AhRR as well as aryl hydrocarbon receptor (AhR), AhR nuclear translocator
      (ARNT) and cytochrome P450 1A1 (CYP1A1) mRNA by real-time TaqMan PCR method.
      First, we examined the expression of these genes in human adult or fetal tissues.
      The levels of AhRR expression were extremely high in testis, very high in lung,
      ovary, spleen and pancreas from adults, whereas those were low in those from
      fetuses. On the other hand, CYP1A1 expression was extremely high in lung, and AhR
      and ARNT were ubiquitously expressed in almost all tissues. Second, we compared
      the expression levels of these genes in mononuclear cells (MNCs) from various
      sources. Comparison of the basal expression levels of these genes in MNCs
      demonstrated that MNCs from umbilical cord blood showed higher AhRR or CYP1A1
      expression than those from adults. The induction of AhRR or CYP1A1 expression by
      3-methylcholanthrene (3-MC) was observed in MNCs from adults but not from
      umbilical cord blood. Consequently, there existed characteristic differences in
      the basal levels of AhRR and CYP1A1 expression in MNCs, as well as in their
      inducibility by 3-MC among MNCs from various types of human bloods. These results
      will provide basic information for a possible application of AhRR and CYP1A1
      measurements to evaluate AH exposure in vivo.

PMID- 14672760
TI  - Protective effect of acteoside on carbon tetrachloride-induced hepatotoxicity.
AB  - This study investigated the protective effects of acteoside, a phenylethanoid
      glycoside, on the carbon tetrachloride-induced hepatotoxicity as well as the
      possible mechanisms involved in this protection in mice. Pretreatment with
      acteoside prior to the administration of carbon tetrachloride significantly
      prevented the increased serum enzymatic activities of alanine and aspartate
      aminotransferase in a dose-dependent manner. In addition, pretreatment with
      acteoside significantly prevented the increase in hepatic malondialdehyde
      formation and the depletion of the reduced glutathione content in the liver of
      carbon tetrachloride-intoxicated mice. Carbon tetrachloride-induced
      hepatotoxicity was also essentially prevented, as indicated by a liver
      histopathologic study. The effects of acteoside on cytochrome P450 (P450) 2E1,
      the major isozyme involved in carbon tetrachloride bioactivation were also
      investigated. Treatment of the mice with acteoside resulted in a significant
      decrease in the P450 2E1-dependent pnitrophenol and aniline hydroxylation in a
      dose-dependent manner. Consistent with these observations, the P450 2El protein
      levels were also lower. Acteoside exhibited anti-oxidant effects on FeCl2
      ascorbate induced lipid peroxidation in a mouse liver homogenate, and on
      superoxide radical scavenging activity. These results suggest that the protective
      effects of acteoside against the carbon tetrachloride-induced hepatotoxicity
      possibly involve mechanisms related to its ability to block the P450-mediated
      carbon tetrachloride bioactivation and free radical scavenging effects.

PMID- 14672761
TI  - The challenge of pancreatic cancer.
AB  - Adenocarcinoma of the pancreas is the fourth leading cause of cancer death in men
      and women in the United States. It affects nearly as many people each year as
      does the human immunodeficiency virus and has a much worse outcome. This article
      reviews the progress in treatment of this disease since 1975, outlines the
      current clinical and research challenges in the field, and suggests a plan of
      action to address these challenges. The world literature in the field since 1975
      was reviewed, and the pancreatic cancer Progress Report Group of the National
      Cancer Institute (NCI) is reviewed and presented. Some progress has been made in
      understanding and treating pancreatic cancer since 1975. Much remains to be done.
      The lack of progress in the field can largely be attributed to the lack of
      importance and subsequent lack of research dollars attributed to it by the NCI.
      The NCI is addressing this issue by proposing to fund Specialized programs of
      research excellence grants in pancreatic cancer. In addition, other mechanisms
      exist within the NCI to allow for additional funding of pancreatic cancer. Using
      the tremendous progress made in the field of human immunodeficiency virus
      research as an example, it is hoped that similar improvements can be made in the
      field of pancreatic cancer if substantial and sustained efforts are made.

PMID- 14672762
TI  - A two institution experience with 226 endoscopically placed jejunal feeding tubes
      in critically ill surgical patients.
AB  - BACKGROUND: Early jejunal feeding after surgery or trauma reduces infectious
      complications. Although not ideal gastric and postpyloric feedings are often
      used, however, because of difficulty in placing feeding tubes distal to the
      ligament of Treitz (LOT). Our hypothesis was that feeding tube placement distal
      to the LOT can be accomplished using a bedside transendoscopic technique.
      METHODS: Transendoscopic jejunal (TEJ) tube placement and TEJ tubes inserted
      simultaneously through percutaneous gastrostomy (PEG) tubes (PEG/TEJ) were
      attempted to be placed distal to the LOT. RESULTS: In all, 226 feeding tubes (185
      TEJ, 41 PEG/TEJ) were placed in 179 trauma and 47 nontrauma patients over 3 years
      (August 20, 1998 to July 15, 2001). Tube location was jejunal in 93.8% of trauma
      patients, 76.6% of nontrauma patients, and 90.3% of all patients. (Confidence
      intervals were 89.3% to 96.5%, 62.8% to 86.4%, and 85.7% to 93.5%). Days of total
      parenteral nutrition were reduced 71.3% in trauma patients, 22.8% in nontrauma
      patients, and 45% overall at one institution. CONCLUSIONS: Bedside TEJ and
      PEG/TEJ placement is safe and successful in placing feeding tubes distal to the
      LOT in more than 90% of critically ill surgical patients.

PMID- 14672763
TI  - Quantitative tracheal lavage versus bronchoscopic protected specimen brush for
      the diagnosis of nosocomial pneumonia in mechanically ventilated patients.
AB  - BACKGROUND: No gold standard method exists for the diagnosis of ventilator
      associated pneumonia despite the availability of multiple techniques. METHODS: A
      prospective, crossover study was performed on mechanically ventilated patients
      meeting with suspected pneumonia. Eighteen paired samples were obtained on 15
      patients, comparing the results of quantitative tracheal lavage (QTL) to
      bronchoscopic protected brush specimen (PSB) by quantitative culture and gram
      stain examination. RESULTS: The sensitivity, specificity, positive and negative
      predictive values, and accuracy are affected by the growth density threshold
      selected, and whether the same organisms are expected by both methods. There is a
      significant relationship between QTL and PSB (P = 0.0048; R = 0.632), gram stain
      and PSB (P <0.001; R = 0.791), and gram stain and QTL (P = 0.0125; R = 0.575), by
      Spearman rank order correlation. CONCLUSIONS: QTL may have a role for diagnosing
      and directing treatment of ventilator-associated pneumonia, allowing reservation
      of bronchoscopic PSB for secondary, high risk and refractory cases.

PMID- 14672764
TI  - Are resuscitation and operation justified in injured patients with extreme base
      deficits (less than -20)?
AB  - BACKGROUND: This study assessed the outcome of injured patients in shock with an
      admission base deficit of -20 or less (approximate pH <7.0) at a level 1 trauma
      center. METHODS: A retrospective review was made of the trauma registry,
      supplemented by chart review, of all trauma patients admitted with a base deficit
      -20 or less from 1995 to 2002. Data collected included mechanism of injury, base
      deficit, Injury Severity Score(ISS), operative procedures, and outcome. Data are
      presented as mean +/- SD. RESULTS: Over the study period, 110 trauma patients
      (88% male; 31 +/- 13 years; 34% blunt trauma; ISS 26 +/- 15) were admitted with
      base deficit of -20 or less. Overall survival was 38%, with the majority of
      deaths occurring within hours of admission. CONCLUSIONS: An admission base
      deficit of -20 or less is associated with high mortality in patients with gunshot
      wounds (64%) or blunt trauma (70%). The majority of patients who die will do so
      within hours of admission. Beyond 24 hours, the survival rates of 73% for
      patients with blunt trauma, 79% for those with gunshot wounds, and 90% for those
      with stab wounds justify continuing resuscitation and reoperations.

PMID- 14672765
TI  - Patients with impending abdominal compartment syndrome do not respond to early
      volume loading.
AB  - BACKGROUND: It is recommended that patients with impending abdominal compartment
      syndrome (ACS) should be volume loaded to insure the adequate preload. We
      evaluated our prospective resuscitation database to determine how patients who
      developed ACS differ from non-ACS patients in response to early volume loading.
      METHODS: Over 36 months, 152 consecutive high-risk patients were resuscitated by
      a standard intensive care unit (ICU) protocol that escalates interventions in
      nonresponders. Interventions, responses, and outcomes are prospectively collected
      and the characteristics of ACS and non-ACS patients were compared. RESULTS:
      Twenty-three patients (15%) developed ACS and were decompressed 8 +/- 1 hours
      after ICU admission. The ACS and non-ACS patients had similar demographics and
      injury severity. The severity of pre-ICU shock tended to be greater in the ACS
      patients. During the first 8 hours of ICU resuscitation, patients who developed
      ACS received more blood transfusions (11 +/- 2 versus 2 +/- 0.2 units; P<0.05)
      and crystalloids (13 +/- 2 versus 4 +/- 0.3 L; P<0.05). As a result, pulmonary
      capillary wedge pressure increased more in the ACS patients (20 +/- 1.5 versus 15
      +/- 0.5 mm Hg; P<0.05), but comparatively the cardiac index did not (3.2 +/- 0.2
      versus 4.2 +/- 0.1 L/min/m(2); P<0.05) and the ACS patients developed pathologic
      elevations of gastric regional CO(2) pressures (70 +/- 7 versus 48 +/- 1 mm Hg
      P<0.05). CONCLUSIONS: Conventional preload directed resuscitation to enhance
      cardiac function is not effective in patients with impending ACS, and this
      traditional resuscitation strategy is detrimental in this subgroup of patients.

PMID- 14672766
TI  - The benefit of routine thoracic, abdominal, and pelvic computed tomography to
      evaluate trauma patients with closed head injuries.
AB  - BACKGROUND: The evaluation of multitrauma patients for blunt truncal injuries
      remains open for debate. We sought to evaluate the role of routine computed
      tomography (CT) of the chest, abdomen, and pelvis as a screening tool for
      patients already undergoing cranial CT studies. METHODS: Charts of blunt trauma
      patients admitted from June 2000 to June 2001 were reviewed for demographics,
      Glascow Coma Scale (GCS), physical and radiological findings, and length of stay.
      RESULTS: Our study found that 38% of patients undergoing cranial CT scanning had
      a unexpected finding on body scans. Changes were made in 26% of the study group
      because results found on the adjuvant CTs. CONCLUSIONS: Additional body CTs add
      minimal cost to the care of trauma patients but can significantly change the
      management. We believe it is beneficial to perform routine body CT examinations
      when performing cranial imaging for blunt head injury.

PMID- 14672767
TI  - Objective indications for early tracheostomy after blunt head trauma.
AB  - BACKGROUND: Early tracheostomy has been shown to be beneficial after trauma;
      however, there are few objective data to identify early in the recovery period
      which patients will ultimately require tracheostomy after blunt head trauma.
      METHODS: The charts of all patients admitted to the surgical intensive care unit
      intubated at a level 1 urban trauma center, over a 5-year period with a primary
      admission diagnosis of blunt head trauma were retrospectively reviewed. RESULTS:
      Sixty-four patients met inclusion and exclusion criteria and were divided into
      two groups: those extubated and those that required tracheostomy. By day 3 the
      Glasgow Coma Scores for the two groups were significantly different and on day 4
      the Simplified Acute Physiology (SAPS) Scores were significantly different.
      CONCLUSIONS: Calculating objective scores such as GCS and SAPS can aid in
      identifying those patients who will ultimately require a tracheostomy for
      prolonged airway protection after blunt head trauma with high positive predictive
      value.

PMID- 14672768
TI  - Surgical management of traumatic pulmonary injury.
AB  - BACKGROUND: Surgical treatment of traumatic pulmonary injuries requires knowledge
      of multiple approaches and operative interventions. We present a 15year
      experience in treatment of traumatic pulmonary injuries. We hypothesize that
      increased extent of lung resection correlates with higher mortality. METHODS:
      Surgical registry data of a level 1 trauma center was retrospectively reviewed
      from 1984 to 1999 for traumatic lung injuries requiring operative intervention.
      Epidemiologic, operative, and hospital mortality data were obtained. RESULTS:
      Operative intervention for traumatic pulmonary injuries was required in 397
      patients, of whom 352 (89%) were men. Penetrating trauma was seen in 371 (93%)
      patients. Location of the injuries was noted in the left side of the chest in 197
      (50%), right side of the chest in 171 (43%), and bilateral in 29 (7%). Operative
      interventions included pneumonorraphy (58%), wedge resection or lobectomy in
      (21%), tractotomy (11%), pneumonectomy (8%), and evacuation of hematoma (2%).
      Overall mortality was 27%. If concomitant laparotomy was required, mortality
      increased to 33%. The mortality rate in the pneumonectomy group was 69.7%.
      CONCLUSIONS: The majority of lung injuries occurred in males due to penetrating
      trauma. Surgical treatment options ranged from simple oversewing of bleeding
      injury to rapid pneumonectomy. Mortality increased as the complexity of the
      operative intervention increased. Rapid intraoperative assessment and appropriate
      control of the injury is critical to the successful management of traumatic lung
      injury.

PMID- 14672770
TI  - Management and short-term patency of lower extremity venous injuries with various
      repairs.
AB  - BACKGROUND: Although several methods of repair of extremity venous injuries have
      been shown to be efficacious, patency rates have varied significantly from center
      to center. METHODS: A retrospective review was made of treatment outcomes of
      adult and pediatric patients with major venous injuries of the lower extremity.
      RESULTS: From 1997 to 2002, 82 patients sustained 86 major lower extremity venous
      injuries. Venous injuries were treated with primary repair in 27, complex repair
      in 37 (autogenous vein, 10, and ringed polytetrafluoroethylene [PTFE], 27) and
      ligation in 20. Prior to repair, temporary intraluminal venous shunts were used
      in 18 patients. Follow-up duplex imaging or venography or both were performed on
      42 extremities at a mean of 10.9 +/- 7.1 days after repair with an overall
      patency rate of 73.8% (primary repair 76.5%; autogenous vein graft 66.7%; and
      PTFE 73.7%). CONCLUSIONS: Overall early patency rate of venous repairs performed
      by an experienced trauma team is similar irrespective of the type of repair. The
      use of temporary intraluminal shunts is acceptable in selected circumstances,
      while ringed PTFE grafts are reasonable alternatives when the contralateral
      saphenous vein is too small.

PMID- 14672769
TI  - A prospective evaluation of interrupted nitinol surgical clips in arteriovenous
      fistula for hemodialysis.
AB  - BACKGROUND: The use of a self-closing nitinol surgical clip (Coalescent Surgical
      U-Clip) is a novel technique of creating an interrupted vascular anastomosis,
      which also eliminates the knot tying associated with a conventional vascular
      anastomosis. The purpose of this study was to compare the clinical outcome of
      arteriovenous fistulae (AVF) for hemodialysis as constructed using interrupted U
      Clip devices and conventional continuous polypropylene sutures. METHODS: We
      prospectively studied the clinical course of 132 patients (149 access) undergoing
      either forearm autologous arteriovenous fistula (FAVF, n = 69) or upper arm
      autologous arteriovenous fistula (UAVF, n = 80) or creations during a 39-month
      period. Among the FAVF, U-Clips and polypropylene sutures were used in 37 and 32
      anastomoses, respectively. Among the UAVF, U-Clips and polypropylene sutures were
      used in 41 and 30 anastomoses, respectively. Primary patency, complication, and
      maturation rates were analyzed. RESULTS: Clipped FAVF had an improved maturation
      rate at 6 weeks (32 of 37, 86%) when compared with sutured FAVF (22 of 32, 69%, P
      <0.05). There was no difference in the maturation rate among UAVF constructed
      with either U-Clips or sutures (88% versus 87%, not significant). The primary
      patency rates at 12, 24, and 36 months were 91%, 84%, and 75% for the clipped
      FAVF; and 83%, 74%, and 61% for the sutured FAVF (P <0.05) There was no
      difference in the patency rate of UAVF constructed with either U-Clips or
      polypropylene sutures at either 12, 24 or 36 moths (91%, 80%, and 75% versus 83%,
      77%, and 69%, respectively). CONCLUSIONS: The U-Clips are a viable alternative to
      sutures for creating vascular anastomosis. It provides a improved maturation and
      patency rates when compared with the conventional sutured AVF in the forearm. The
      clinical benefit of the U-Clips may be due in part to the improved compliance
      created by the interrupted anastomotic technique.

PMID- 14672771
TI  - Clinical benefits of leukocyte filtration during valve surgery.
AB  - BACKGROUND: The accumulation of activated leukocytes in the pulmonary circulation
      plays an important role in the pathogenesis of lung dysfunction associated with
      cardiopulmonary bypass (CPB). Patients undergoing valve surgery have prolonged
      CPB owing to the complexity of the surgery. The goal of this study is to
      determine if arterial leukocyte filters during CPB improve clinical outcomes
      after valve surgery. METHODS: A prospective analysis of all patients receiving
      only valve surgery with leukocyte arterial filters from June 1999 to June 2002
      was compared with a case matched cohort during the same time period. Two hundred
      fifty patients were identified and compared with a cohort who did not have
      leukocyte filters used during CPB. The following study points were evaluated
      preoperatively and postoperatively: white blood cell count, platelet count,
      arterial blood gas, time to extubation, intensive care unit stay, and total
      length of hospital stay. RESULTS: There were 500 patients in the study. The
      following valve operations were performed: 92 mitral valve replacements, 168
      aortic valve replacements, 152 mitral valve repairs, 80 combined valve
      repair/replacements, and 8 tricuspid valve repairs, all evenly divided between
      the two treatment limbs. Patients with leukocyte filters had the following
      findings compared with nonfilter patients: The time to extubation 10.3 versus
      16.2 hours (P = 0.009), postoperative respiratory quotient 407 versus 320 (P =
      0.02), total length of stay 5.4 versus 7.2 days (P = 0.04). CONCLUSIONS: The use
      of arterial leukocyte filters in patients undergoing valve surgery leads to
      earlier extubation, improved oxygenation, and a decreased length of stay.
      Leukocyte filters should be used during CPB for patients having valve surgery.

PMID- 14672772
TI  - Surgical outcome in 85 patients with primary cardiac tumors.
AB  - BACKGROUND: We present a large, single institution experience with adult cardiac
      tumors and address factors affecting outcome. METHODS: A retrospective review was
      made of all patients who underwent surgery for primary cardiac tumors from April
      1975 through August 2002. RESULTS: Eighty-five patients (33 male and 52 female)
      with a mean age of 54 years were identified with follow-up available for 80 (94%)
      patients. There were 68 (80%) benign tumors and 17 (20%) malignant tumors. Three
      tumors recurred and were resected giving a total of 88 surgeries. All benign
      tumors were grossly resected and the extent of resection for malignant disease
      ranged from 14 (78%) gross resections and 3 (17%) debulkings to 1 (5%) biopsy.
      There were 4 (5%) early hospital deaths. Median survival was 9.6 months and 322
      months for patients with malignant and benign diseases, respectively. Significant
      predictors of long-term mortality were malignant disease (P <0.0001) and New York
      Heart Association class (P <0.03). CONCLUSIONS: Surgical resection provides
      excellent outcome in patients with benign cardiac tumors. Malignant tumors
      continue to pose a challenge with good local tumor control but limited survival
      owing to metastatic disease.

PMID- 14672773
TI  - Conversion of laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: To determine the incidence and causes of conversion from a
      laparoscopic to an open gastric bypass for morbid obesity, we reviewed the
      experience of our bariatric center. METHODS: We performed a retrospective review
      of the records of consecutive patients undergoing laparoscopic Roux-en-Y gastric
      bypass at our center. RESULTS: In all, 1,236 consecutive patients with body mass
      indes (BMI) from 35 to 82 were approached laparoscopically. In 97%, bypasses were
      completed laparoscopically and in 3% (40 patients), a conversion was required to
      complete the procedure. Older age and male sex were greater in the converted
      group, whereas BMI was not different nor was the proportion of super obese
      patients. The cause of conversion was technical in 80%, bleeding in 10%, and a
      massive liver in 10%. CONCLUSIONS: Our risk of conversion was generally low, but
      increased in older patients and males. In 33% of patients, conversions could have
      been avoided with technical lessons learned by experience.

PMID- 14672774
TI  - Efficacy of laparoscopic antireflux surgery in patients with Barrett's esophagus.
AB  - BACKGROUND: Laparoscopic antireflux surgery (LARS) corrects significant
      physiologic and anatomic abnormalities in patients with gastroesophageal reflux
      disease (GERD); however, debate exists whether LARS prevents recurrent symptoms
      and malignant transformation in patients with Barrett's esophagus (BE). This
      study compared clinical outcomes after LARS in patients with and without BE.
      METHODS: From 1994 to 2001, 448 patients who underwent LARS were studied. Of
      these, 68 (15%) had preoperative evidence of BE with low-grade dysplasia in 3
      (4%), and 380 (85%) were without BE. Mean postoperative follow-up was more than
      30 months in each group. RESULTS: After LARS, there was equivalent reduction in
      acid reduction medication use and typical GERD symptoms in both groups. Anatomic
      failures developed in 12% of patients with BE and in 5% of those without BE (P =
      0.05). Upper endoscopy with biopsies was obtained in 50 of 68 patients (74%) with
      BE at 37 +/- 22 months postoperatively. Intestinal metaplasia was no longer
      present in 7 of 50 (14%) BE patients, and low-grade dysplasia regressed to
      nondysplastic Barrett's in 2 of 3 patients. New low-grade dysplasia developed in
      1 BE patient (2%) at postoperative endoscopic surveillance. No BE patients
      developed high-grade dysplasia or adenocarcinoma. CONCLUSIONS: After LARS,
      patients with BE have symptomatic relief and reduction in medication use
      equivalent to non-BE patients. Regression of intestinal metaplasia and the
      absence of progression to high-grade dysplasia or adenocarcinoma suggest that
      LARS is an effective approach for the management of patients with Barrett's
      esophagus. The higher failure rate of LARS in BE is of concern and mandates
      ongoing follow-up of these patients.

PMID- 14672775
TI  - The role of pelvic exenteration in the management of recurrent rectal cancer.
AB  - BACKGROUND: Use of extirpative surgery in the setting of recurrent rectal cancer
      is controversial given the poor overall outcome of such patients and the
      morbidity associated with exenteration. METHODS: A retrospective review of
      patients treated for recurrent rectal cancer from 1990 to 2002 was performed.
      RESULTS: Twenty-two patients underwent pelvic exenteration. Seventeen underwent
      potentially curative resection, 5 were for palliation only. There was 1 operative
      death. Fifteen suffered at least 1 complication; 9 suffered multiple
      complications. Ten patients required readmission to the hospital. The overall
      disease-free interval was 11 months. Potentially curative and palliative
      resections resulted in median survivals of 20.4 and 8.4 months, respectively (P =
      0.049). CONCLUSIONS: While patients may derive oncologic and palliative benefits
      from exenteration, the price in terms of operative morbidity remains high. Newer
      measures of operative morbidity are necessary to better appraise the value of
      this radical approach to recurrent rectal cancer.

PMID- 14672776
TI  - Is there a role for surgery in patients with "unresectable" cKIT+
      gastrointestinal stromal tumors treated with imatinib mesylate?
AB  - BACKGROUND: Imatinib mesylate (Gleevec) is being studied as adjuvant chemotherapy
      for the treatment of cKIT+ gastrointestinal stromal tumors (GISTs). Early reports
      using Gleevec for the treatment of unresectable GISTs have shown 50% to 60%
      partial response rates based on radiographic evaluation alone. No study has yet
      correlated radiographic response with pathologic findings. This retrospective
      review of patients with cKIT+ GISTs who received Gleevec prior to surgical
      resection examines the pathologic response to therapy and the feasibility of
      surgical resection after treatment. METHODS: Patients with cKIT+ GISTs were
      identified from the institutional sarcoma database. Patients were included if
      they had pathologic confirmation of cKIT mutation and therapy with Gleevec. The
      pretreatment and preoperative radiographs, surgeons' operative notes, and
      pathology reports were reviewed for documentation of the extent of disease.
      RESULTS: Between January 2001 and Octorber 2002, 126 patients with unresectable
      cKIT + GISTs treated with Gleevec were identified. Of these 126 patients, 17 have
      subsequently undergone surgical resection after a median of 10 months (range 2 to
      16) of treatment with Gleevec. Based on computed tomographic (CT) scanning, 1
      (6%) patient had evidence of a complete tumor response, 12 (70%) patients had a
      partial response, 3 (24%) patients had stable disease, and 1 (6%) patient had
      progressive disease. Posttreatment/preoperative CT imaging documented an overall
      response rate of 76%. The pathologic review of the operative specimens showed
      that 2 (12%) patients had a complete response to therapy, 11 (65%) had a partial
      response to therapy, 3 (18%) patients had no evidence of treatment effect on the
      excised tumor, 1 patient had progressive disease. Sixteen patients (94%)
      underwent complete surgical resection of disease, including 3 patients with no
      pathologic evidence of response to therapy. One patient had progression of
      disease and was unresectable at surgical exploration. CONCLUSIONS: This series is
      the first to present pathologic data after the treatment of cKIT+ GISTs with
      Gleevec. In this series, the majority of responses were limited to partial
      responses, indicating that surgical resection remains a vital component of the
      treatment plan for patients with cKIT+ GISTs. This series is consistent with
      previous reports indicating that complete responses are extremely rare in
      response to treatment with Gleevec. Patients with advanced disease may benefit
      from a course of neoadjuvant therapy with Gleevec followed by resection, even
      when there is evidence of multifocal disease. A prospective evaluation of
      neoadjuvant Gleevec therapy for advanced cKIT+ GISTs is warranted.

PMID- 14672777
TI  - Transsacral exenteration of fixed primary and recurrent anorectal cancer.
AB  - BACKGROUND: Posteriorly fixed anorectal cancer is often considered incurable, but
      may be resectable using transsacral approaches. METHODS: We reviewed 45 patients
      undergoing transsacral exenteration for this problem since 1983 to determine
      outcome of such surgery. RESULTS: The group consisted of 38 men and 7 women; 17
      had primary tumors, 28 had recurrent cancer: local excision, 1; low anterior
      resection, 11; or abdominoperineal resection, 16. Thirty-nine had prior XRT.
      Operative mortality was 4%. Severe pain was relieved in 16 of 22 (72%) patients.
      Crude recurrence rates are local 22%, local plus distant 11%, distant 16%. Five
      year disease-free survival is 31% for primary disease, 32% for recurrence. Median
      survival is abdominoperineal resection recurrence, 24 months; primary cancer, 30
      months; low anterior resection recurrence, 37 months. CONCLUSIONS: Transsacral
      exenteration relieved pain in 70% of patients with fixed anorectal cancer, and
      led to long-term survival in 31% to 32%. Prognosis trended toward benefit for
      recurrence after low anterior resection.

PMID- 14672778
TI  - Patterns of recurrence after sentinel lymph node biopsy for cutaneous melanoma.
AB  - BACKGROUND: Previous sentinel lymph node (SLN) studies for cutaneous melanoma
      have shown that the SLN accurately reflects the nodal status of the corresponding
      nodal basin. However, there are few long-term studies that describe recurrence
      site patterns, predictors for recurrence, and overall survival and disease-free
      survival after SLN biopsy. METHODS: A retrospective review of patients over a 6
      year period was performed to determine patient outcomes and the patterns of
      recurrence. In all cases, Tc-99 sulfur colloid along with isosulfan blue dye was
      injected at the primary melanoma site. After resection, the SLN was serially
      sectioned and evaluated by hematoxylin and eosin staining and
      immunohistochemistry. RESULTS: One hundred ninety-eight patients were identified
      who underwent SLN biopsy for cutaneous melanoma including T1 (n = 21), T2 (n =
      88), T3 (n = 75), and T4 (n = 14) primary tumors. Of these patients, 38 had a
      positive SLN. Of the 38 patients with a positive SLN (mean follow-up 38 months),
      recurrent disease was identified in 10 (26.3%) at a mean interval of 14.2 months.
      The site of first recurrence was distant (n = 4) and local (n = 6). Regional
      lymphatic basin recurrence was not identified. Of the 160 patients with a
      negative SLN (mean follow-up 50 months), recurrent disease was identified in 16
      (10.0%) at a mean interval of 31.3 months. The site of first recurrence was
      systemic (n = 11), local (n = 4), and nodal (n = 1). Overall survival and disease
      free survival for patients with a positive SLN at 55 months was 53.3% and 47.7%
      respectively, while overall survival and disease-free survival for patients with
      a negative SLN at 53 months was 92.2% and 87.7% respectively (P <0.01).
      Univariate and multivariate analysis of the entire cohort (n = 198) identified
      primary tumor depth and positive SLN status as significant predictors of
      recurrence. CONCLUSIONS: The incidence of nodal basin recurrence after SLN biopsy
      was found to be 0.6%. Primary tumor depth and pathological status of the SLN are
      significant predictors of local and systemic recurrence. Long-term follow-up
      indicates that patients with a positive SLN clearly recur sooner and have
      decreased overall survival than those with a negative SLN.

PMID- 14672779
TI  - Is appendiceal computed tomography in a community hospital useful?

PMID- 14672780
TI  - Is delayed operative treatment worth the trouble with perforated appendicitis is
      children?
AB  - BACKGROUND: Approximately 30% to 50% of appendicitis in children is already
      perforated at presentation. The optimal management of these children remains
      controversial. METHODS: Ninety-six children (aged 2 to 16 years) were treated for
      perforated appendicitis. Seventy-one underwent immediate appendectomy and
      drainage of abscess, if present (group I). In the other 25 an attempt was made to
      treat with intravenous antibiotics, combined with transrectal (4) or percutaneous
      (2) drainage of abscess. This treatment was successful in 16 patients (group II),
      who underwent appendectomy 6 to 8 weeks later, and unsuccessful in 9 patients
      (group III), who underwent appendectomy 3 to 12 days later. RESULTS: The mean
      length of stay was as follows: group I, 6.7 days; group II, 8.9 days; and group
      III, 10.9 days (not significant). The white blood cell count (WBC) at
      presentation was group I, 18.6 K; group II, 17.9 K; group III, 18.8 K. The
      percent fall of WBC on day 4 was group I, 55%; group II, 25.5%; group III, 17% (P
      >0.05 versus groups I and II). Twenty of 71 patients in group I (28%) developed
      wound infection (5), pelvic abscess (14), and pancreatitis (1), while 2 of 16
      (12.5%) of group II and 1 of 9 (11%) of group III patients required readmission
      (both P <0.05 versus group I). CONCLUSIONS: These data show that initial
      antibiotic treatment of perforated appendicitis in children, followed by interval
      appendectomy, is useful for a select group who present with little or no
      peritonitis, slightly elevated temperature, and WBC that falls at least 25%
      within 3 to 4 days.

PMID- 14672781
TI  - Further experience with gastric stimulation to treat drug refractory
      gastroparesis.
AB  - BACKGROUND: Gastric electrical stimulation (GES) has been introduced for patients
      with gastroparesis refractory to pharmacological therapy. METHODS: From April
      1998 until November 2001, 55 patients underwent GES implantation at Kansas
      University Medical Center. All patients had prolonged gastric retention of a
      solid meal by scintigraphy at baseline. The etiologies were diabetes mellitus in
      39, related to previous surgery in 9, and idiopathic in 7. Symptoms were graded
      using a 5-point scale and quality of life was assessed with the SF-36
      questionnaire. Body mass index and nutritional parameters were monitored.
      Hemoglobin A1C was measured in the diabetic patients. RESULTS: Total symptom
      scores and the physical and mental composite scores of quality of life improved
      significantly. On average, gastric emptying did not change. Body mass index and
      body weight increased significantly. And days spent in hospital admissions were
      significantly decreased. At 1 year, diabetic patients experienced reduced
      hemoglobin A1C. Four devices were removed. One patient died of a pulmonary
      embolus postoperatively. CONCLUSIONS: In a large series of patients with
      gastroparesis, GES significantly improved symptoms and quality of life.

PMID- 14672782
TI  - Spectrum of disease and outcome of complicated diverticular disease.
AB  - BACKGROUND: Diverticular disease is a common entity. The presentation,
      investigations performed, and management are variable. Our objectives were to
      assess the presentation, extent of disease, and treatment of a cohort of patients
      with colonic diverticulitis. METHODS: All patients with a diagnosis of
      diverticulitis over a 9-year period were reviewed. Patients were assessed as to
      age, sex, presenting symptoms, diagnostic studies, extent of disease, treatment,
      and outcome. RESULTS: Over a 9-year period (1992 to 2001), 192 patients were
      admitted with a diagnosis of colonic diverticulitis. The mean age was 61 years
      (range 28 to 90); 113 of 192 (59%) were female. The mean duration of symptoms
      prior to presentation was 14 days (range 1 to 270 days). One hundred eighteen of
      192 (61%) had a previous documented attack of diverticulitis. Of the
      investigations performed 128 of 192 (66.7%) had a computed tomography (CT) scan
      of the abdomen and pelvis, 37 of 192 (20%) underwent a contrast enema, 61 of 192
      (32%) underwent colonoscopy and 2 of 192 (1%) underwent a small bowel series. The
      abnormal findings on the CT scan were as follows: diverticular abscess (16%),
      diverticulitis (37%), diverticulosis without inflammation (15%), free air (10%)
      and fistula (1%). The locations of the diverticular abscesses were: pelvic (36%),
      pericolic sigmoid (36%), and "other," which included interloop (28%).
      Preoperative abscess drainage occurred in 10 of 192 (5%), which were either
      percutaneous, 6 of 192 (3%), or transrectal, 4 of 192 (2%). Nine of 192 (6%)
      presented with a fistula, colovesical fistulae (3%), colocutaneous (1%),
      enterocolic (1%), or colovaginal (1%). Overall, 73 of 192 (38%) underwent
      surgery. All patients undergoing surgery had a resection of their colon. The
      operative findings were localized abscess in 16 of 73 (22%), purulent/feculent
      peritonitis in 12 of 73 (17%), and phlegmon in 10 of 73 (14%). Sixty-seven of 73
      (92%) had a primary resection with anastomosis; 38 of 67 (56%) had a protecting
      stoma. Five of 73 (7%) patients were found to have an unsuspected carcinoma.
      Overall, 29 of 192 (15%) developed a complication related to diverticulitis.
      Morbidity was 15.1%, of which 34% was infection related. Four of 192 patients
      (2%) died. CONCLUSIONS: In our experience, most patients presented with abdominal
      pain predominantly in the left lower quadrant. The symptoms were present on
      average of 14 days, most were female (59%), and most patients had a previous
      attack of diverticulitis. The commonest investigation performed was a CT scan
      (66.7%); however, other investigations were performed, for example, barium
      enemas. The practice of resection and primary anastomosis for acute
      diverticulitis has an acceptable morbidity and mortality. For high-risk
      anastomoses, a covering loop ileostomy and not a Hartmann's procedure is
      preferred. Surgery remains safe for the majority of patients and is associated
      with resolution of symptoms. We believe that because of the high number of
      patients in our series who had a previous attack of diverticulitis, therapy
      should be focused on preventing recurrent and virulent attacks by earlier
      operative intervention.

PMID- 14672783
TI  - Fine-needle aspiration of the thyroid and correlation with histopathology in a
      contemporary series of 240 patients.
AB  - BACKGROUND: False-positive, false-negative, and indeterminate fine-needle
      aspiration (FNA) biopsy results complicate the management of patients with
      thyroid nodules. METHODS: Thyroid FNA results from 240 consecutive patients (seen
      1991 to 2002) were categorized into four groups: positive for malignancy,
      negative for malignancy, indeterminate for malignancy, and nondiagnostic.
      Indeterminate results included follicular neoplasm, Hurthle cell neoplasm, and
      suspicious for papillary carcinoma. The FNA results were compared with
      histopathologic analysis after thyroidectomy. RESULTS: The FNA results were 76
      (32%) positive for malignancy, 53 (22%) negative for malignancy, 100 (42%)
      indeterminate for malignancy, and 11 (5%) nondiagnostic. There were 3 (4%) false
      positive and 2 (4%) false-negative FNA results. Among the 100 indeterminate FNA
      results, carcinoma was found in 11 (15%) of 73 follicular neoplasms, 2 (20%) of
      10 Hurthle cell neoplasms, and 14 (82%) of 17 suspicious for papillary carcinoma.
      For the 73 patients with follicular neoplasms, nodule diameter >2 cm was
      associated with an increased risk of malignancy (P <0.03). CONCLUSIONS: False
      negative FNA results are uncommon, supporting the practice of observation in most
      of these patients. Among those with indeterminate biopsy results, high-risk
      subgroups include patients with FNA results suspicious for papillary carcinoma
      and follicular neoplasms >2 cm.

PMID- 14672784
TI  - Potential role for intraoperative gamma probe identification of normal
      parathyroid glands.
AB  - BACKGROUND: Patients undergoing central neck surgery are at risk for
      hypoparathyroidism. We hypothesized that gamma probe identification of sestamibi
      labeled parathyroid glands might help maximize parathyroid preservation. METHODS:
      Records of 351 patients who underwent central neck surgery were reviewed. A
      subgroup of patients underwent sestamibi injection followed by gamma probe
      directed parathyroid gland identification. RESULTS: Operation was performed for
      malignancy in 73% of patients and represented a reoperation in 34%. Persistent
      hypoparathyroidism was more common in patients who underwent reoperation versus a
      primary operation (6.8% versus 1.7%; P = 0.02). Thirteen patients underwent gamma
      probe-directed identification of sestamibi-labeled parathyroid glands; in 6 of
      these patients, sestamibi-labeled parathyroid glands were salvaged from the
      resected specimens and autografted. None of these 13 patients developed
      persistent hypoparathyroidism. CONCLUSIONS: Patients undergoing reoperative
      central neck surgery are at increased risk for postoperative hypoparathyroidism.
      Gamma probe-directed salvage of sestamibi-labeled parathyroid glands may help
      maximize parathyroid preservation, especially in complex or reoperative central
      neck surgery.

PMID- 14672785
TI  - An assessment of the severity of recurrent appendicitis.
AB  - BACKGROUND: This study examines the clinical characteristics of patients who
      developed recurrent appendicitis after previous nonoperative management of
      perforated appendicitis. METHODS: Retrospective chart review was performed, and
      data from the recurrent and initial episode of appendicitis were collected.
      RESULTS: In all, 237 patients from 1989 to 2001 were managed nonoperatively for
      perforated appendicitis and 32 (14%) were readmitted for recurrent appendicitis.
      Median white blood cell count at recurrence was 9.5 (interquartile range [IQR]:
      6.6 to 13.2] versus 13.1 [IQR: 10.8 to 16.1] at initial presentation (P = 0.002).
      Maximum temperature was 98.6 degrees F [IQR: 98.2 to 100.5] at recurrence versus
      100.3 degrees F [IQR: 99.5 to 101.5] (P = 0.008). Median time for intravenous
      antibiotics use was 3 [IQR: 3 to 7] days at recurrence versus 6 [IQR: 4 to 8]
      days initially (P = 0.01). Inpatient stay was also shorter; median length was 6
      [IQR: 3 to 8] days compared with 7 [IQR: 5 to 9] days at initial presentation (P
      = 0.02). CONCLUSIONS: Patients managed nonoperatively for perforated appendicitis
      who later developed recurrent appendicitis exhibited a milder clinical course at
      recurrence. Elective interval appendectomy may be reserved until a recurrent
      episode.

PMID- 14672786
TI  - Local and national trends over a decade in the surgical treatment of ductal
      carcinoma in situ.
AB  - BACKGROUND: Ductal cancer in situ (DCIS) is an increasingly frequent diagnosis in
      breast cancer, and management continues to challenge surgeons and oncologists.
      The purpose of our study was to examine local and national rates of breast
      conservation surgery and breast reconstruction surgery and to explore patient and
      surgeon factors associated with the procedures. METHODS: Review of the 1,342
      patients in our institutional breast cancer database yielded 211 patients with
      DCIS. The sample of 211 patients was compared with a national (Nationwide
      Inpatient Sample [NIS]) database. Patient and surgeon factors associated with the
      use of breast conservative surgery (BCS) and breast reconstruction (BR)
      postmastectomy were identified. RESULTS: At our institution, the use of BCS
      steadily increased over ten years. Younger women with nonpalpable tumors,
      nonprivate insurance, and younger surgeons were more likely to have BCS. In 28
      patients, breast reconstruction was performed: younger Caucasian women with
      private insurance and younger surgeons were more likely to undergo
      reconstruction. NIS data revealed that BCS was performed in 20% but that BCS did
      not increase over the 12-year period. CONCLUSIONS: There was a steady increase in
      the use of BCS for DCIS at our institution, but a consistent, and much lower, use
      nationally. To increase breast conservation and reconstruction for DCIS,
      educational efforts should especially be directed toward elderly women and
      elderly surgeons.

PMID- 14672787
TI  - Subareolar sentinel node biopsy for multiple breast cancers.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) is deemed suitable only for
      unifocal breast cancers since multiple foci of cancers may drain to different
      nodes. We hypothesized that subareolar injection (SI) could identify the sentinel
      lymph nodes (SLN) accurately in patients with multiple cancers (MC) in the
      breast. METHODS: We prospectively employed SI of lymphazurin or technetium sulfur
      colloid, or both, for the identification of SLN in patients with MC in the
      breast. All patients underwent axillary dissection to compute the accuracy of
      SLNB. RESULTS: Forty patients presented with MC in the same breast between
      January 1996 and July 2002. Fifty-two percent (21 of 40) of patients had
      involvement of more than 1 quadrant; 18% (7 of 40) had more than 1 histologic
      type of cancers. SLNs were successfully identified in 100% of patients. Axillary
      disease was present in 63% (25 of 40) of patients. Sensitivity of SLNB was 100%
      and false negative rate was 0%. The SLN was the only node involved in 45% (18 of
      40) of patients. CONCLUSIONS: SLNB using the SI technique may be an alternative
      to complete axillary dissection in patients with multiple breast cancers.

PMID- 14672788
TI  - Touch preparation of breast core needle specimens is a new method for same-day
      diagnosis.
AB  - BACKGROUND: Touch preparation cytology (TPC) has proven to be a quick and
      accurate intraoperative diagnostic tool for excisional breast biopsy, margins and
      sentinel nodes. We hypothesized that TPC of core needle biopsy (CNB) specimens
      can provide a same-day diagnosis in the outpatient setting. METHODS: Outpatients
      presenting with breast lesions underwent TPC of biopsy cores performed by biopsy
      gun or vacuum-assisted CNB. The TPC results were compared with the final
      diagnosis of CNB specimens. RESULTS: In all, 199 CNB and TP were performed
      between August 1997 and October 2002. Twenty-nine percent of lesions were
      malignant. Touch preparation was deferred in 21% of cases. In the remaining 157
      evaluable cases, TPC had an accuracy of 89% and a false negative rate of 26%. The
      sensitivity, specificity, positive predictive value and negative predictive value
      of TPC were 74%, 97%, 93%, and 86% respectively. CONCLUSIONS: Touch preparation
      cytology on CNB can be performed simply in the outpatient setting. Collaboration
      between the surgeon and pathologist allows TP to be an accurate means of same-day
      pathological determination.

PMID- 14672789
TI  - Diverticulitis in the younger patient.
AB  - BACKGROUND: The purpose of this study was to examine the presentation of
      diverticulitis at an urban county hospital serving predominantly indigent
      patients and to analyze the differences, if any, in presentation and treatment in
      younger patients. METHODS: A retrospective review of medical records from 1995 to
      2001 was performed at a single institution to identify patients admitted to the
      surgical service with the diagnosis of diverticular disease. Inclusion criteria
      were either diverticulitis confirmed at operation or radiographic findings
      consistent with the disease. Patient demographics, history, pertinent physical
      findings, and treatment were recorded. The data were analyzed after dividing the
      patients into two populations: a younger population 50 years of age or less, and
      a second population of patients older than 50. RESULTS: During the interval, a
      total of 64 patients were admitted to the surgical service with the diagnosis of
      diverticulitis. The mean age of this population was 45.5 years (range 21 to 86).
      Forty-six patients were under 50 years of age (72%). Analysis of sex differences,
      type and timing of surgical procedure, and complication rate with respect to age
      showed no significant difference between the two age groups. CONCLUSIONS: We are
      clearly treating a younger patient population than previous reports on patients
      with diverticulitis. Although there was a trend toward increased surgical
      intervention in the younger population, this number did not reach statistical
      significance. Diverticulitis in young patients at our institution does not appear
      to take a more aggressive course than the same disease in older patients.

PMID- 14672790
TI  - Small bowel transit and gastric emptying after biliodigestive anastomosis using
      the uncut jejunal loop.
AB  - BACKGROUND: The Roux-en-Y loop is an effective procedure for biliodigestive
      drainage. However, up to 15% of patients suffer from postoperative cholangitis or
      blind loop syndrome. A new technique to prevent motility abnormalities has been
      developed. METHODS: Male Lewis rats were used to compare gastric emptying and
      transit in the small bowel after either a standard Roux-en-Y anastomosis or a new
      biliodigestive anastomosis technique which involves creating an "uncut" jejunal
      loop with luminal occlusion. Unoperated rats served as controls. (99)Technetium
      HIDA and (111)Indium-tagged amberlite were respectively used to investigate small
      bowel transit and gastric emptying. RESULTS: Histopathology showed distinctive
      abnormalities only in the liver of conventional Roux-en-Y animals. No
      recanalization of the obliterated gut lumen occurred in uncut Roux animals.
      Distribution of (99)Tc-HIDA and (111)In showed were similar in both groups.
      Gastric emptying is slowed in both groups. CONCLUSIONS: The uncut proximal
      jejunum loop is a good alternative to the conventional Roux-en-Y loop and showed
      preserved small bowel motility and adequate jejunal transit. Gastric emptying is
      slowed in both groups.

PMID- 14672791
TI  - On the periodicity of manic-depressive insanity, by Eliot Slater (1938):
      translated excerpts and commentary.
AB  - Since the classic descriptions of the course of bipolar and recurrent depressive
      forms of manic-depressive illness by Emil Kraepelin a century ago, it has been
      considered a truism that the rate of cycling increases, and wellness intervals
      shorten, with rising counts of recurrences, particularly early in the natural
      history of the illness. Less well known is that the analysis of this phenomenon
      is vulnerable to a computational artifact first described by Eliot Slater, based
      on his reanalysis of data from manic-depressive patients first evaluated by
      Kraepelin at the Munich Psychiatric Institute. Slater realized that there is an
      increasingly disproportionate representation of faster-cycling patients in sub
      samples involving higher cycle-counts in pooled samples of subjects. More
      accurate results require analyzing illness-course either within individuals, or
      in groups matched for episode-counts. This artifact is pervasive in the older and
      modern research literature, but still not widely recognized. Since Slater's 1938
      report in German is not well known, we provide an abbreviated English translation
      with commentary and additional reanalysis to highlight the phenomenon that might
      be termed 'Slater's Fallacy'.

PMID- 14672792
TI  - Cyclic time patterns of death from suicide in northern Finland.
AB  - BACKGROUND: Time patterns of suicide have been attributed not only to social and
      psychological factors but also to direct geophysical effects. Seasonal variations
      in day length and temperature seem likely to contribute to the timing of the
      suicide process. METHODS: We analysed all suicides (n=1658) committed in a
      northern province of Finland during a period of 153 months. Daily data on the
      number of suicides, local weather conditions and geomagnetic storms were compiled
      and modelled with Poisson regression using the province population as the
      denominator, and with the means of harmonic series for seasonal variation. Time
      series analysis of monthly numbers of suicides was carried out using the seasonal
      trend decomposition procedure based on loess. RESULTS: Marked fluctuations in the
      number of suicides occurred during the study period (P=0.01). There was
      significant seasonal variation in death from suicide (P=0.01), but analysis of
      the meteorological data showed no evidence of effect on the risk of suicide.
      LIMITATIONS: Assessment of mental disorder or alcohol consumption was missing,
      since only data derived from death certificate was available for each case.
      CONCLUSIONS: The seasonal effect was significant, but remained modest compared to
      sex and age as risk factors for suicide. Preventive measures need to be tailored
      according to time of the year.

PMID- 14672793
TI  - QT dispersion in patients with social phobia.
AB  - BACKGROUND: QT dispersion (QTd) is the maximal interlead difference in QT
      interval on the surface 12-lead electrocardiogram (ECG). An increase in QTd is
      found in various cardiac diseases and reflects cardiac autonomic imbalance. It
      has recently been associated with increased anxiety levels, thereby predisposing
      affected individuals to fatal heart disease. This is the first study to assess
      QTd in social phobia, as a marker of anxiety-induced cardiac dysregulation.
      METHODS: QTd and rate-corrected QTd were measured in 16 physically healthy and
      non-depressed outpatients with long-term (mean 28+/-12.2 years; age 37.9+/-9.6
      years) social phobia (SP) and in 15 physically and mentally healthy age- and
      gender-matched controls. The Liebowitz Social Anxiety Scale (LSAS) was scored
      concomitantly. The intra- and inter-observer reproducibilities of QTd were highly
      correlated (r=0.96, P<0.001; r=0.74, P=0.002, respectively). RESULTS: QTd and
      rate-corrected QTd were significantly higher in the patients with SP compared to
      the controls (70+/-21 versus 43+/-10 ms, P<0.001 and 75+/-23 versus 46+/-10 ms,
      P<0.001, respectively), and highly correlated with the two LSAS subscores.
      CONCLUSIONS: Prolonged SP is associated with an increase in QTd. This association
      may result from prolonged anxiety and, in turn, a decrease in vagal modulation
      and/or increase in sympathetic modulation. Further large-scale epidemiological
      studies are needed to determine if increased QTd can serve as a trait/state
      marker, and if it is a risk factor for sudden cardiac death in patients with SP.

PMID- 14672794
TI  - Symptoms of depression in the Estonian population: prevalence, sociodemographic
      correlates and social adjustment.
AB  - OBJECTIVE: The current study presents data on the prevalence of depressive
      symptoms in the Estonian population and examines associated sociodemographic
      factors and subjective aspects of social adjustment. METHOD: The data came from
      the Estonian Health Interview Survey where 4711 persons aged 15-79 were
      interviewed. This study included 4677 respondents who answered the Emotional
      State Questionnaire (EST-Q), a self-rating scale of depression and anxiety. Data
      on the sociodemographic factors and domains of social adjustment were derived
      from structured interviews. RESULTS: Depressive symptoms were observed in 11.1%
      of the respondents. Depressiveness was more common among women, in older age
      groups, among those not married, in ethnic groups other than Estonians, in lower
      income groups, and among the unemployed and economically inactive respondents.
      Depressive subjects were less satisfied, had a more pessimistic prognosis about
      the future and lower self-rated health. A low level of perceived control was a
      significant correlate of depression. The association of depressiveness with poor
      subjective social adjustment remained significant even after controlling for
      objective circumstances. LIMITATIONS: Depression was identified by a self-rate
      questionnaire, therefore results can not be generalized to clinical depression
      without caution. CONCLUSION: Depressive symptoms in the Estonian population were
      strongly related to socioeconomic functioning. Results emphasize that subjective
      social adjustment and perceived control are important characteristics of
      depression and should be considered in assessment and treatment.

PMID- 14672795
TI  - Partial posttraumatic stress disorder revisited.
AB  - BACKGROUND: It is thought that the decision rule for a positive diagnosis of
      Posttraumatic Stress Disorder (PTSD) may be too restrictive, leaving too many
      victims of a trauma out in the cold for care, compensation, etc. Several authors
      have proposed the concept of Subthreshold or Partial PTSD (PPTSD). This concept
      considers that a subject may present a number of symptoms below threshold for
      criteria C or D (subthreshold syndromes) and may even present without any symptom
      for one or more of the criteria B, C and D (partial syndromes). METHOD: Data have
      been collected by means of the Composite International Diagnostic Interview
      (CIDI) PTSD-module, in a group exposed to two different traumatic events (130
      fire victims and 55 car accident victims). The syndrome patterns has been
      assessed by means of hierarchical class analyses. Each of the criteria B, C and D
      has been analyzed separately, showing the symptom patterns as hierarchically
      order clusters. RESULTS: Depending on the threshold used for criterion C (i.e. 3
      or 2 symptoms), 18.4 and 22.7% of the subjects respectively satisfy the criteria
      for PTSD. 8.7% of the subjects show subthreshold syndromes. 60.7% of the subjects
      show partial syndromes and 16.7% of the subjects have partial syndromes while
      fulfilling criterion F, i.e. a clinically significant impairment in functioning.
      CONCLUSIONS: The results show a considerable number of partial and subthreshold
      syndromes. It is argued that subthreshold syndromes and partial syndromes, which
      fulfill criterion F, should be regarded as specific nosological categories or as
      specified PTSD subcategories, i.e. subsyndromal or partial PTSD.

PMID- 14672796
TI  - High prevalence of mental disorders in primary care.
AB  - OBJECTIVE: To determine the prevalence of common mental disorders in an adult
      primary care population. DESIGN: Cross-sectional survey in randomly selected
      subjects, using the PRIME-MD questionnaire. SETTING: Eighty-six general practices
      in Belgium. SUBJECTS: A total of 2316 randomly selected patients, aged 18 years
      or older and consulting their general practitioner for other than administrative
      reasons alone, with slightly more women (58.1%) than men (41.3%). MAIN OUTCOME
      RESULT: Prevalence rates of mental disorders most commonly seen in primary care
      practice (mood, anxiety, somatoform, eating and alcohol disorders). METHODS: To
      facilitate data collection and processing, the entire PRIME-MD questionnaire was
      programmed on a handheld computer. Patient answers and physician assessments were
      immediately electronically recorded during the interview. All investigators were
      trained on the use of the PRIME-MD. The recruitment period lasted 6 weeks: from
      15 February to 25 March 1999, and patients were randomly selected for the
      interview based on a computerized procedure. RESULTS: Although only 5.4% of all
      patients consulted for a psychiatric reason, a threshold/subthreshold psychiatric
      disorder was detected in 42.5% of all patients. Most commonly detected disorders
      were mood disorders in 31.0% (major depressive disorder, 13.9% and dysthymia,
      12.6%), anxiety disorders in 19.0% (generalized anxiety disorder, 10.3%),
      somatoform disorders in 18.0% and probable alcohol abuse/dependence in 10.1%. The
      results also showed the important rate of comorbidity between these disorders.
      CONCLUSION: The present study confirms the high prevalence of mental disorders in
      a general practice setting, and their frequent association. Prevalence rates of
      our study are even higher than those obtained in previously conducted trials. Our
      study also demonstrates the utility of the PRIME-MD as a screening tool for
      mental disorders in primary care. In addition the use of the handheld computer
      software version of the PRIME-MD allowed us to screen for mental disorders in
      patients who are unable to attend the GP office and are seen during 'home'
      visits.

PMID- 14672797
TI  - Correlates of insight among patients with bipolar I disorder in remission.
AB  - BACKGROUND: The aims of this study were to explore the levels of insight in a
      group of bipolar patients in remission and to investigate factors related to
      capacity for insight. METHODS: Using the Schedule of Assessment of Insight (SAI)
      and its expanded version (SAI-E), we interviewed 65 patients with bipolar I
      disorder in remission to determine their levels of insight. Multiple regression
      analysis was used to examine the factors that influenced insight. RESULTS: Our
      results revealed that most of our bipolar subjects had fair or good insight,
      though some residual insight impairment was still observed. Multiple regression
      analysis revealed that being male, having a shorter duration of illness and
      having psychotic features predicted poorer insight in two dimensions of SAI and
      SAI-E, accounting for 18.6-23% of the variance. LIMITATIONS: The six independent
      variables used in these multiple regression could only account in part for the
      variance of insight, indicating that there must be other variables that influence
      insight of bipolar patients in remission. CONCLUSIONS: These results indicated
      that bipolar patients with the factors predicting poor insight should possibly
      receive interventions to improve their insight and advance their recovery.

PMID- 14672798
TI  - Autobiographical memory predicts the course of depression during detoxification
      therapy in alcohol dependent men.
AB  - BACKGROUND: Recall of autobiographical memories (AM) has shown to predict the
      course of depression during psychiatric treatment [British Journal of Psychiatry
      162 (1993)]; therefore, we assume that AM also predicts the remissive course of
      depression during detoxification therapy in alcohol dependent men. METHODS: In a
      longitudinal study, 65 patients were assessed twice: at admission to a
      detoxification unit and about 3 weeks later for follow-up. AM scores at the
      beginning of the detoxification program were used as predictors in hierarchical
      regression analyses. RESULTS: After controlling for initial depression, mental
      status and degree of alcohol dependence, AM in response to positive and
      aggressive cue words significantly predicted affective change. These results
      validate the assumption that AM is a psychological depression marker.
      LIMITATIONS: No data are reported on depression prior to drinking onset.
      CONCLUSIONS: As a practical consequence, AM can assist the physician with the
      decision for concomittant antidepressive therapy during detoxification and
      rehabilitation of alcohol dependent men.

PMID- 14672800
TI  - Burden of dysthymia and comorbid illness in adults in a Canadian primary care
      setting: high rates of psychiatric illness in the offspring.
AB  - BACKGROUND: The burden of comorbid dysthymia and other comorbid psychiatric
      illnesses in a Canadian primary care setting was measured. Two groups of primary
      care patients: those who scored positive for comorbid dysthymia versus those who
      scored negative for any psychiatric disorder were compared. METHODS: This was a
      cross-sectional survey in a Health Service Organization (HSO) in Ontario, Canada.
      The subjects were patients of the HSO. The main outcome measures were: health
      status, mood, social adjustment, coping ability, children's psychiatric
      disorders, child development, family function, and health and social service
      utilization. RESULTS: Of the 6280 eligible adults who were patients at the HSO,
      68.9% consented to be screened for psychiatric disorders; 5.1% screened positive
      for dysthymia, of which 90% had at least one comorbid psychiatric disorder. The
      following statistically significant differences were found between people with
      dysthymia and other comorbid psychiatric disorders versus people without any
      psychiatric disorder. People with dysthymia were more likely to have worse health
      status, worry more about their health, and report levels of pain that impaired
      their function; they had higher MADRS depression scores, lower social role
      function scores, lower social adjustment scores, and lower coping ability. More
      children of people with comorbid dysthymia met criteria for one or more childhood
      psychiatric disorders and there were more families with a parent with dysthymia
      that were dysfunctional. People with dysthymia used a greater proportion of
      health and social services, had higher per person annual health care costs
      (excluding hospital services), and had higher per person annual indirect costs
      (lost wages). CONCLUSION: This analysis demonstrated the burden of illness and
      costs that this disorder imposes on individuals, their families, and society as a
      whole.

PMID- 14672799
TI  - Psychopathology in the adolescent offspring of bipolar parents.
AB  - BACKGROUND: The aim of this study was to determine the prevalence and 14-months
      incidence of psychopathology in adolescent offspring of a bipolar parent. METHOD:
      Parent, teacher and self-report rating scales and Kiddie-SADS were used to assess
      132 13-23-year-old offspring of bipolar parents. RESULTS: Compared to the general
      population, there were few differences between rating scale scores for bipolar
      offspring and problem scores for normative adolescents. Of the sample 49% had a
      lifetime psychiatric disorder, most commonly (33%) a mood disorder. LIMITATIONS:
      There was no suitable control group and there are no comparison data for
      psychiatric diagnoses (DSM-IV), based on semi-structured interviews in the
      adolescent age group in the Netherlands. CONCLUSIONS: The overall level of
      psychopathology of bipolar offspring was not particularly elevated, but when
      there were more problems, they tended to be mood disorders.

PMID- 14672801
TI  - Earlier onset of bipolar disorder in children by antidepressants or stimulants?
      An hypothesis.
AB  - Among adults and adolescents, bipolar disorder (BD) has a similar prevalence in
      the US and in the Netherlands. However, among pre-pubertal children, BD is
      frequently diagnosed in the US and seldomly in the Netherlands. This suggests
      that, among children, the prevalence of BD is lower in the Netherlands than in
      the US, indicating an earlier onset of BD in the US than in the Netherlands. It
      is hypothesized that this may be related to the greater use of antidepressants
      and stimulants for depression or attention deficit disorder with hyperactivity by
      US children. In those children who are genetically at risk to develop BD, these
      drugs may lead to a switch into mania.

PMID- 14672802
TI  - The usefulness of therapeutic sleep deprivation in depression.

PMID- 14672804
TI  - Zonal expression and activity of glutathione S-transferase enzymes in the mouse
      olfactory mucosa.
AB  - The rodent olfactory mucosa is characterized by a mosaic of gene expression that
      is exhibited among various cell types. Olfactory sensitivity in these animals is
      conveyed through odorant receptor families that are distinctly expressed within
      various subsets of the olfactory neuron population. Receptor neurons that express
      a particular class of odorant receptors exhibit bilaterally symmetric zones,
      which generally define their location within the nasal cavity. Less characterized
      are zonal expression profiles of proteins among non-neuronal cell types of the
      olfactory mucosa. In this study, we survey the expression of three glutathione S
      transferase (GST) isozymes (alpha, mu, and pi) in the mouse olfactory mucosa and
      characterize the zonal expression of the mu isozyme. Immunohistochemistry and
      Western blot analysis of the GST mu isozyme reveal that the lateral olfactory
      turbinates I, Ib, II, IIb, and III display a greater intensity of expression for
      GST mu, in comparison to the dorsal and septal regions of the mucosa. GST alpha
      and pi isozymes do not display any distinct zonal organization in olfactory
      tissue of the adult mouse. When the general substrate 1-chloro-2-4-dinitrobenzene
      (CDNB) was used to assess GST activity within the olfactory tissue, the lateral
      turbinate regions displayed a higher level of activity when compared to dorsal or
      septal regions. Analysis of GST mu expression in prenatal and early postnatal
      olfactory tissue also reveals a zonal expression of the isozyme. We relate the
      significance of these findings to metabolic topography and olfactory chemosensory
      function.

PMID- 14672805
TI  - The occurrence of vacuolation, and periodic acid-Schiff (PAS)-positive granules
      and plaques in the brains of C57BL/6J, AKR, senescence-prone (SAMP8) and
      senescence-resistant (SAMR1) mice infected with various scrapie strains.
AB  - Scrapie is a fatal, but slow, infectious disease. C57BL/6J, SAMP8 (a strain that
      develops early senescence), SAMR1 (a strain that is resistant to senescence) and
      AKR/J (a progenitor of the SAM strains) mice were infected with 22A, 139A, 22L
      and ME7 scrapie strains. Histopathological stains included haematoxylin and eosin
      (HE), and periodic acid-Schiff (PAS). Vacuolation was found in the brains of all
      scrapie-infected mice. The 22A strain caused more extensive vacuolation in the
      brains of SAMP8 and SAMR1 mice than in C57BL mice. PAS-positive plaques (PP) were
      found in 22A-infected mice in cortex, corpus callosum, hippocampus, subependymal
      zone area and thalamus. PP were significantly increased in 22A-infected SAMR1
      mice compared to mice from other scrapie-infected strains. Clusters of small,
      round, homogeneous PAS-positive granular structures (PGS) were found in all mouse
      strains, especially in aging control and 22A-infected C57BL mice, predominantly
      in the stratum radiatum of the CA1, CA2 and CA3 areas of the hippocampus. Some of
      these structures were also observed in stratum oriens and piriform cortex, and in
      cerebellar Purkinje cell areas. Some of the PGS were associated with astrocytes
      and blood vessels. Each granule was 1-5 microm in diameter and there were
      clusters consisting of several to 40 PGS; the sizes of the clusters ranged from
      10 to 80 microm in diameter. There were more PGS clusters in uninfected C57BL and
      AKR mice than in uninfected SAMP8 and SAMR1 mice. PGS were not increased in
      scrapie-infected mice. These findings suggest that PGS accumulation was more
      dependent on the genetic information of the mouse strain, whereas PP and
      vacuolation patterns depended on the scrapie strain-mouse strain combination.

PMID- 14672806
TI  - Effect of repeated administration of TRK-820, a kappa-opioid receptor agonist, on
      tolerance to its antinociceptive and sedative actions.
AB  - Repeated administration of micro-opioid receptor agonist, morphine induces
      tolerance not only to the antinociceptive effect but also to other
      pharmacological effects, resulting in shortened working duration and decreased
      efficacy. But less is known about kappa-opioid agonist-induced tolerance. The
      tolerance-development potency of kappa-opioid receptor agonists with a focus on
      TRK-820 was characterized. After five administrations of kappa-opioid receptor
      agonists, TRK-820 (0.1-0.8 mg/kg), U-50,488H (10-80 mg/kg) and ICI-199,441 (0.025
      0.2 mg/kg) subcutaneously over 3 days, tolerance to the antinociceptive effects,
      assessed by an acetic acid-induced abdominal constriction test, developed in a
      repeated dose-dependent manner. The tolerance-development potency of TRK-820 was
      the least among these kappa-opioid receptor agonists. Similarly, TRK-820 and U
      50,488H induced tolerance to their sedative effects as judged by a wheel-running
      test in mice. Greater tolerance was developed to the sedative effect than to the
      antinociceptive effect in both compounds. After repeated administration, the
      number of kappa-opioid receptors in the mouse brain was reduced by U-50,488H (80
      mg/kg) but not by TRK-820 (0.4 mg/kg). There was no change of the affinity by the
      treatment with both compounds. These results demonstrated that the kappa-opioid
      receptor agonists developed tolerance both to the antinociceptive and the
      sedative effects, though the tolerance to the sedative effect developed more
      readily than tolerance to the antinociceptive effect. The difference in the
      potency for down-regulating the kappa-opioid receptors in the brain may account
      for the tolerance-development potency of the compounds.

PMID- 14672807
TI  - [3H]Resiniferatoxin autoradiography in the CNS of wild-type and TRPV1 null mice
      defines TRPV1 (VR-1) protein distribution.
AB  - Knowledge of the distribution and function of the vanilloid receptor (VR-1 or
      TRPV1) in the CNS lacks the detailed appreciation of its role in the peripheral
      nervous system. The radiolabelled vanilloid agonist [3H]resiniferatoxin (RTX) has
      been used to indicate the presence of TRPV1 receptor protein in the brain but low
      specific binding has complicated interpretation of this data. Recently, support
      for a more widespread CNS distribution of TRPV1 mRNA and protein has been
      provided by RT-PCR and antibody data. We have exploited the availability of TRPV1
      null mice and used [3H]RTX autoradiography in the CNS of TRPV1 wild-type and
      TRPV1 null mice to identify the component of [3H]RTX binding to TRPV1 receptor
      protein. In the brains of TRPV1+/+ mice, specific [3H]RTX binding was broadly
      localised with the greatest binding in the olfactory nuclei, the cerebral cortex,
      dentate gyrus, thalamus, hypothalamus, periaqueductal grey, superior colliculus,
      locus coeruleus and cerebellar cortex. Specific binding was also seen in the
      spinal cord and sensory (dorsal root and trigeminal) ganglia. This binding was
      much lower but not abolished in most regions in the TRPV1-/- mice. Nonspecific
      binding was low in all cases. The present study unequivocally demonstrates a
      widespread and discrete distribution pattern of the TRPV1 receptor protein in the
      rat central nervous system. The presence of TRPV1 receptors in several brain
      regions suggests that it may function as a cannabinoid-gated channel in the CNS.

PMID- 14672808
TI  - Tyrosine phosphatase inhibition induces loss of blood-brain barrier integrity by
      matrix metalloproteinase-dependent and -independent pathways.
AB  - Tight junctions between endothelial cells of brain capillaries form the
      structural basis of the blood-brain barrier (BBB), which controls the exchange of
      molecules between blood and CNS. Regulation of cellular barrier permeability is a
      vital and complex process involving intracellular signalling and rearrangement of
      tight junction proteins. We have analysed the impact of tyrosine phosphatase
      inhibition on tight junction proteins and endothelial barrier integrity in a
      primary cell culture model based on porcine brain capillary endothelial cells
      (PBCEC) that closely mimics the BBB in vitro. The tyrosine phosphatase inhibitor
      phenylarsine oxide (PAO) induced increased matrix metalloproteinase (MMP)
      activity, which was paralleled by severe disruption of cell-cell contacts and
      proteolysis of the tight junction protein occludin. ZO-1 and claudin-5 were not
      affected. Under these conditions, the transendothelial electrical resistance
      (TEER) was markedly reduced. PAO-induced occludin proteolysis could be prevented
      by different MMP inhibitors. Pervanadate (PV) reduced the TEER similar to PAO,
      but did not increase MMP activity. Cell-cell contacts of PV-treated cells
      appeared unaffected, and occludin proteolysis did not occur. Our results suggest
      that tyrosine phosphatase inhibition can influence barrier properties independent
      of, but also correlated to MMPs. Evidence is given for a role of MMPs in
      endothelial tight junction regulation at the BBB in particular and probably at
      tight junctions (TJs) in general.

PMID- 14672809
TI  - Temporal organization of the 24-h corticosterone rhythm in the diurnal murid
      rodent Arvicanthis ansorgei Thomas 1910.
AB  - Arvicanthis ansorgei is a diurnal murid rodent from sub-Saharan Africa. The
      present study reports on the temporal organization of one of the major hormonal
      rhythms, i.e. the adrenal steroid hormone corticosterone, in an attempt to
      characterize further the diurnal nature of this species. The data were obtained
      by means of two different physiological methods: blood sampling and intracerebral
      microdialysis. The results show a 12-h rhythm of corticosterone release with peak
      values close to the light-dark (ZT10) and dark-light transition (ZT22-24), which
      is clearly different from that in a nocturnal animal. Both corticosterone peaks
      are closely correlated with the occurrence of two major bouts of running wheel
      activity. As far as we are aware, this is the first demonstration of a hormonal
      rhythm with a clear crepuscular appearance (peak values around dusk and dawn). In
      conclusion, these data show that also in a rodent with a diurnal/crepuscular
      activity pattern, the tight association between the daily corticosterone peak and
      the onset of activity is maintained. In addition, intracerebral microdialysis is
      a suitable technique to measure hormonal rhythms when repeated blood sampling is
      not possible.

PMID- 14672810
TI  - Distribution of hypocretin (orexin) immunoreactivity in the feline pons and
      medulla.
AB  - The distribution of hypocretin-1 (hcrt-1) and hypocretin-2 (hcrt-2)
      immunoreactivities in the cat brainstem was examined using immunohistochemical
      techniques. Hcrt-1- and hcrt-2-positive fibers with varicosities were detected in
      almost all brainstem regions. However, no hcrt-1- or hcrt-2-immunoreactive
      neuronal somata were observed in the cat brainstem. Both hcrt-1- and hcrt-2
      labeled fibers exhibited different densities in distinct regions of the
      brainstem. In most brainstem regions, the intensity of hcrt-1 immunoreactivity
      was higher than that of hcrt-2 immunoreactivity. The highest densities of hcrt-1-
      and hcrt-2-positive fibers were found in the nucleus raphe dorsalis (RD), the
      laterodorsal tegmental nucleus (LDT) and the locus coeruleus (LC), suggesting an
      important role for these peptides in functions related to sleep-wake behavior.

PMID- 14672811
TI  - Hyperglycemia and hypercapnia differently affect post-ischemic changes in protein
      kinases and protein phosphorylation in the rat cingulate cortex.
AB  - Hyperglycemia and hypercapnia aggravate intra-ischemic acidosis and subsequent
      brain damage. However, hyperglycemia causes more extensive post-ischemic damage
      than hypercapnia, particularly in the cingulate cortex. We investigated the
      changes in the subcellular distribution of protein kinase Cgamma (PKCgamma) and
      the Ca2+/calmodulin-dependent protein kinase II (CaMKII), as well as changes in
      protein tyrosine phosphorylation during and following 10 min normoglycemic,
      hyperglycemic (plasma glucose approximately 20 mM) and hypercapnic (paCO2)
      approximately 300 mm Hg) global cerebral ischemia. During reperfusion period, the
      translocation to cell membranes of PKCgamma, but not CaMKII, was prolonged by
      intra-ischemic hyperglycemia, while it was only marginally affected by
      hypercapnia. The tyrosine-phosphorylation of proteins in the synaptosomal
      membranes, as well as the extracellular signal-regulated kinase (ERK) in the
      cytosol, markedly increased during reperfusion following hyperglycemic ischemia,
      but to a lesser degree following hypercapnic ischemia. Our data suggest that
      PKCgamma, tyrosine kinase and ERK systems are involved in the process of ischemic
      damage in the cingulate cortex, where hyperglycemia may affect these kinases
      through an additional mechanism other than exaggerated acidosis.

PMID- 14672812
TI  - Differential projections from the mediodorsal and centrolateral thalamic nuclei
      to the frontal cortex in rats.
AB  - The aim of the present study was to investigate afferent projections from the
      medial thalamic nuclei (MT) to the frontal cortical areas using a single small
      iontophoretic injection of biotinylated dextran amine (BDA) and analysis of the
      anterogradely labeled fibers and varicosities. Projections from the mediodorsal
      (MD) nuclei were found primarily and extensively in the anterior cingulate cortex
      (ACC), whereas those from the centrolateral (CL) thalamic nucleus were found in
      the frontal motor cortex. The density of terminals in the ACC was high in layers
      II and III and sparse in layer I. The majority of projected fibers from the CL
      were found at a high density in layer V, with a moderate density in the
      superficial layers. The differential projection patterns were topographically
      organized in the medial prefrontal cortex and sensory motor cortex. These
      findings support the results of our previous electrophysiological studies
      suggesting that neurons in the medial thalamic nuclei relay nociceptive
      information to the limbic or sensory motor cortical areas. The present results
      agree with the current notion that the medial thalamo-frontal cortical network
      circuitry plays an important role in processing the emotional aspect of
      nociception.

PMID- 14672813
TI  - Dopamine-induced synaptic depression in the parabrachial nucleus is independent
      of CTX- and PTX-sensitive G-proteins, PKA and PLC signalling pathways.
AB  - We have previously reported that dopamine (DA) depresses non-NMDA receptor
      mediated glutamatergic transmission in the rat parabrachial nucleus (PBN), an
      interface between brainstem and forebrain that is implicated in autonomic
      regulation. This work examined cellular signalling pathways that might underlie
      this DA-induced synaptic depression. Direct activation of adenylyl cyclase with
      10 microM forskolin increased the evoked EPSC but did not occlude DA-induced EPSC
      depression. Similarly, a preferential protein kinase A inhibitor, H-7 (10
      microM), did not block DA's synaptic effects. Incubation of slices with cholera
      toxin (CTX; 1 microgram/ml) or pertussis toxin (PTX; 0.5 microgram/ml) for 20 h,
      procedures used to irreversibly activate or disable the G(s) and G(i) proteins,
      respectively, did not change DA's effects. The putative phospholipase C
      inhibitor, U-73122 (10 microM) and its inactive analogue U-73343 (10 microM) did
      not alter DA-induced reduction in the EPSCs. Alterations in signalling molecules
      downstream of phospholipase C including depleting internal calcium stores by
      thapsigargin and cyclopiazonic acid and blocking protein kinase C with
      chelerythrine, had no effect on DA-induced synaptic depression. Furthermore, DA's
      depression of the non-NMDA response was not blocked by APV, an NMDA receptor
      antagonist. Finally, DA depressed evoked, pharmacologically isolated NMDA
      receptor-mediated synaptic responses while increasing NMDA-induced inward
      currents in the PBN. These results indicate that DA-induced synaptic effects in
      the PBN are not through the activation of cholera or pertussis toxin sensitive G
      proteins. Furthermore, it does not employ the adenylyl cyclase-cAMP-PKA cascade,
      the phospholipase C signalling pathway and NMDA receptor-coupled mechanisms to
      depress excitatory synaptic transmission in the PBN.

PMID- 14672814
TI  - Effect of tetramethylpyrazine on acute nociception mediated by signaling of P2X
      receptor activation in rat.
AB  - Tetramethylpyrazine (TMP) has been used in traditional Chinese medicine as an
      analgesic for dysmenorrhea. In the present study, we try to investigate the
      effects of TMP on acute nociception mediated by P2X receptor activation of rat
      hindpaw and the membrane depolarization of rat dorsal root ganglion (DRG) neurons
      induced by P2X receptor agonists. The subcutaneous administration of TMP (0.1-10
      mmol) into rat hindpaw in a dose-dependent manner decreased acute paw flinching
      responses mediated by adenosine 5'-triphosphate (ATP, 1000 nmol) or alpha,beta
      methylene ATP (alpha,beta-meATP, 600 nmol). The subcutaneous administration of
      TMP (5 or 10 mmol) into rat hindpaw inhibited significantly the first phase of
      nociceptive behaviors induced by 5% formalin and attenuated slightly the second
      phase of nociceptive behaviors induced by 5% formalin. The subcutaneous
      administration of TMP (10 mmol) into rat hindpaw reduced the nociceptive
      responses induced by alpha,beta-meATP (200 nmol) co-injected with Prostaglandin
      E2 (PGE2), 5 micromol). The membrane depolarization induced by ATP (200 micromol)
      or alpha,beta-meATP (50 micromol) in DRG neurons was inhibited by TMP (300
      micromol). The data suggest that the antinociceptive effect of TMP is involved in
      blocking the signaling of P2X3 receptor activation in rat.

PMID- 14672815
TI  - Increasing of intrathecal CSF excitatory amino acids concentration following
      morphine challenge in morphine-tolerant rats.
AB  - Excitatory amino acids (EAAs) are involved in the development of opioid
      tolerance. The present study reveals that an increasing of CSF EAAs concentration
      might be responsible for the losing of morphine's antinociceptive effect in
      morphine tolerant rats. Male Wistar rats were implanted with two intrathecal
      (i.t.) catheters and one microdialysis probe, then continuously infused i.t. for
      5 days with saline (1 microl/h; control group), morphine (15 micrograms/h), the
      NMDA antagonist, MK-801 (5 micrograms/h), or morphine (15 micrograms/h) plus MK
      801 (5 micrograms/h). Each day, tail-flick responses were measured; in addition,
      CSF dialysates were collected and CSF amino acids measured by high performance
      liquid chromatography using a fluorescence detector. Morphine started to lose its
      analgesic effect on day 2 and this effect was overcome by MK-801. The AD(50) (AD:
      analgesic dose) was 1.33 micrograms in control animals, 83.83 micrograms in
      morphine-tolerant rats (a 63-fold shift), and 11.2 micrograms (a 8.4-fold shift)
      in rats that had received MK-801 plus morphine. No significant differences were
      observed in CSF amino acid release between the groups from day 1 to day 5. On day
      5, after basal dialysate collection, a 10-micrograms challenge of morphine was
      administered i.t., and CSF samples collected over the next 3 h. After morphine
      challenge, morphine-tolerant rats showed a significant increase in the release of
      glutamate and aspartate (131+/-9.5% and 156+/-12% of basal levels, respectively),
      and no antinociceptive effect in the tail-flick latency test, while MK
      801/morphine co-infused rats showed no increase in morphine-induced EAA release
      and a partial antinociceptive effect (MPE=40%). The present study provides direct
      evidence for a relationship between EAA release and a lack of an antinociceptive
      response to morphine, and shows that the NMDA antagonist, MK-801, attenuates both
      of these effects.

PMID- 14672816
TI  - Neuraminidase inhibitor, oseltamivir blocks GM1 ganglioside-regulated excitatory
      opioid receptor-mediated hyperalgesia, enhances opioid analgesia and attenuates
      tolerance in mice.
AB  - The endogenous glycolipid GM1 ganglioside plays a critical role in nociceptive
      neurons in regulating opioid receptor excitatory signaling demonstrated to
      mediate "paradoxical" morphine hyperalgesia and to contribute to opioid
      tolerance/dependence. Neuraminidase (sialidase) increases levels of GM1, a
      monosialoganglioside, in these neurons by enzymatic removal of sialic acid from
      abundant polysialylated gangliosides. In this study, acute treatment of mice with
      the neuraminidase inhibitor, oseltamivir enhanced morphine analgesia. Acute
      oseltamivir also reversed "paradoxical" hyperalgesia induced by an extremely low
      dose of morphine, unmasking potent analgesia. In chronic studies, co
      administration of oseltamivir with morphine prevented and reversed the
      hyperalgesia associated with morphine tolerance. These results provide the first
      evidence indicating that treatment with a neuraminidase inhibitor, oseltamivir,
      blocks morphine's hyperalgesic effects by decreasing neuronal levels of GM1. The
      present study further implicates GM1 in modulating morphine analgesia and
      tolerance, via its effects on the underlying excitatory signaling of Gs-coupled
      opioid receptors. Finally, this work suggests a remarkable, previously
      unrecognized effect of oseltamivir-which is widely used clinically as an
      antiviral agent against influenza-on glycolipid regulation of opioid excitability
      functions in nociceptive neurons.

PMID- 14672817
TI  - Ischemic preconditioning does not improve neurological recovery after spinal cord
      compression injury in the rat.
AB  - Ischemic preconditioning (IPC) has been defined as the endogenous cellular
      protective mechanism evoked by brief ischemic periods. IPC renders the tissue of
      the central nervous system more resistant to subsequent lethal ischemic insults,
      and similar protective effect of IPC has been observed after experimental
      traumatic brain injury. Spinal cord trauma differs from cerebral trauma in that
      the secondary processes are damaging mostly the white matter. In the present
      study, we have tested the hypothesis that a transient non-lethal ischemic insult
      would improve outcomes after subsequent traumatic spinal cord injury (SCI). In
      the IPC group, 5-min spinal cord ischemia has been induced by aortic occlusion
      combined with hypotension. Forty-eight hours after IPC, moderate spinal cord
      injury has been induced by epidural balloon inflation at T8 level. Control group
      underwent identical surgical procedures without ischemia followed by SCI after 48
      h. During the 4-week survival, locomotor performance of all rats was repeatedly
      tested and evaluated according to BBB scale. After 4 weeks, the animals were
      perfusion-fixed for histopathology, and morphometric analyses were performed in
      order to quantify the extent of the spinal cord lesion. All animals were
      completely paraplegic after SCI, and showed partial neurological recovery during
      their survival period. No significant differences were detected either in
      neurological scores or in morphometric measurements after 4 weeks' survival.
      These results indicate that in contrary to cerebral trauma, IPC does not improve
      the outcome after SCI.

PMID- 14672818
TI  - Nitric oxide synthesis inhibition increases proliferation of neural precursors
      isolated from the postnatal mouse subventricular zone.
AB  - The subventricular zone (SVZ) of rodents retains the capacity to generate new
      neurons throughout the entire life of the animal. Neural progenitors of the SVZ
      survive and proliferate in vitro in the presence of epidermal growth factor
      (EGF). Nitric oxide (NO) has been shown to participate in neural tissue formation
      during development and to have antiproliferative actions, mediated in part by
      inhibition of the EGF receptor. Based on these findings, we have investigated the
      possible effects of endogenously produced and exogenously added NO on SVZ cell
      proliferation and differentiation. Explants were obtained from postnatal mouse
      SVZ and cultured in the presence of EGF. Cells migrated out of the explants and
      proliferated in culture, as assessed by bromodeoxyuridine (BrdU) incorporation.
      After 72 h in vitro, the colonies formed around the explants were constituted by
      cells of neuronal or glial lineages, as well as undifferentiated progenitors.
      Immunoreactivity for the neuronal isoform of NO synthase was observed in neuronal
      cells with long varicose processes. Cultures treated with the NOS inhibitor
      N(omega)-nitro-L-arginine methyl ester (L-NAME) showed an increase in the
      percentage of BrdU-immunoreactive cells, whereas treatment with the NO donor
      diethylenetriamine-nitric oxide adduct (DETA-NO) led to a decrease in cell
      proliferation, without affecting apoptosis. The differentiation pattern was also
      altered by L-NAME treatment resulting in an enlargement of the neuronal
      population. The results suggest that endogenous NO may contribute to postnatal
      neurogenesis by modulating the proliferation and fate of SVZ progenitor cells.

PMID- 14672819
TI  - Effects of hypoxia and putative transmitters on [Ca2+]i of rat glomus cells.
AB  - Dissociated rat glomus cells were loaded with Fura-2 AM to study the effects of
      hypoxia, and carotid body transmitters on intracellular calcium, [Ca2+]i. The
      mean control [Ca2+]i was 55 nM in isolated cells and 67 nM in clusters. The
      following procedures changed [Ca2+]i:0[Ca2+]o+EGTA reduced [Ca2+]i by about 50%,
      suggesting that the remaining calcium originated from intracellular organelles.
      [Ca2+]i increased when [Ca2+]o was doubled. Hypoxia by sodium dithionite
      (Na2S2O4) induced large [Ca2+]i increases in clustered and isolated cells.
      Smaller rises occurred with 100% N2 hypoxia. The augmented [Ca2+]i, induced by
      Na2S2O4, was reduced (not eliminated) in 0[Ca2+]o+EGTA, suggesting that some
      calcium was intracellularly released. Nifedipine depressed (did not block) the
      Na2S2O4-induced calcium increase, implying some inflow via other (N, T or P/Q)
      voltage-dependent or voltage-independent calcium channels.Cholinergic agents
      (ACh, nicotine, muscarine, bethanechol and pilocarpine) increased [Ca2+]i. The
      ACh effect was produced exclusively by calcium inflow since it was eliminated in
      0[Ca2+]o+EGTA. Cholinergic effects were depressed (not obliterated) by D
      tubocurarine (D-TC), hexamethonium (C6) and atropine.ACh, nicotine and
      pilocarpine potentiated the excitatory effect of Na2S2O4 on [Ca2+]i. Bethanechol
      depressed this excitation whereas muscarine had inconsistent effects. Atropine
      and C6 depressed [Ca2+]i increases elicited by Na2S2O4 but the effects of D-TC
      were variable. Dopamine (DA) had variable effects. It increased [Ca2+]i in 75% of
      cases, and reduced the Na2S2O4 -induced calcium increase.Thus, calcium increases
      during Na2S2O4 occur by direct effects on the glomus cells and feedback action
      through released ACh and DA.

PMID- 14672820
TI  - Effect of L-Dopa on the pattern of movement-related (de)synchronisation in
      advanced Parkinson's disease.
AB  - In the early stages of Parkinson's disease (PD), impaired motor preparation has
      been related to a delay of mu rhythm movement-related desynchronisation,
      suggesting hypoactivation of the contralateral, primary sensorimotor (PSM)
      cortex. Following movement, a decrease in the amplitude of beta rhythm movement
      related synchronisation was observed over the same region. This decrease--not
      seen in control subjects--was thus thought to be related to an impairment in
      cortical deactivation. By monitoring movement-related (de)synchronisation, we
      aimed (i) to extend to advanced PD the observations made in less-advanced
      situations and (ii) to test the effect of acute L-Dopa on these abnormalities.
      The United Parkinson's Disease Rating Scale (UPDRS) III score decreased by about
      60% following acute L-Dopa administration, and we observed the following
      concurrent changes: a marked increase in mu desynchronisation pre-movement
      latency (thus reduced delay) during movement preparation over contralateral,
      central regions; an increase in mu desynchronisation during movement execution
      over bilateral central regions; a decrease in mu desynchronisation latency over
      bilateral frontocentral regions, and a significant increase in beta
      synchronisation over contralateral, central regions after movement. Changes of mu
      and beta rhythm parameters seemed to be inversely correlated with bradykinesia.
      Mu rhythm desynchronisation latency and beta synchronisation amplitude further
      decreased in advanced PD compared to earlier stages of the disease, suggesting
      greater impairment of cortical activation/deactivation as the disease progresses.
      L-Dopa partially restored the abnormal mu and beta rhythm cortical
      (de)synchronisation patterns over the PSM cortex.

PMID- 14672821
TI  - The effect of aging on postural stability: a cross sectional and longitudinal
      study.
AB  - AIMS OF THE STUDY: Only a good knowledge of the effects of age on postural
      stability allows differentiating between physiological aging and pathologies
      leading to its impairment. The aims of this study were to define the
      posturographic parameters which best reflected the effects of aging on postural
      stability and to determine the slope of postural stability impairment related to
      aging. PATIENTS AND METHODS: Postural stability of 50 normal volunteers aged 25
      83 years (55.4) was studied with one Kistler force plate. Subjects were asked to
      stand for 30 s on two-legged stance, eyes open then closed. The center of
      pressure displacement (COPd) and velocities (COPv), in the antero-posterior (x)
      and the medio-lateral (z) axis, the sway axis, and the integral of COP
      displacement vs. time were computed. Eleven subjects were retested at 3 and 6
      months to estimate the reliability of posturographic measurements. In addition,
      28 subjects aged 25-83 years (60.2) were retested 2.2 years after their first
      posturographic assessment. RESULTS: COPxv best reflected postural stability
      impairment with aging. Closure of the eyes increased the variance of the results.
      This change was higher in subjects more than 60 years old: 0.019-0.157 cm2 s(-2)
      than in younger ones: 0.011-0.043 cm2 s(-2). Retesting at 3 and 6 months showed a
      reliability of 79%. According to the cross-sectional part of the study, the slope
      of postural stability impairment with aging was estimated at 0.0038 cm/s/year.
      These results were confirmed by the longitudinal part of the study, which showed
      that COPxv increased from 0.66-0.75 cm/s/year (P = 0.0001) (slope = 0.0041
      cm/s/year). CONCLUSION: (1) Measurement of COPxv, on two-legged stance, is a
      simple and reliable way to assess postural stability. (2) Thanks to both a cross
      sectional and a longitudinal study, the rate of postural stability impairment due
      to aging was precisely estimated, which will be useful to help distinguishing
      between the part of postural stability impairment attributable to aging from the
      one due to neuro-degenerative diseases.

PMID- 14672822
TI  - Ulnar nerve entrapment at wrist associated with carpal tunnel syndrome.
AB  - In this study, ulnar nerve entrapments at the wrist were investigated using nerve
      conduction studies in cases with established diagnosis of carpal tunnel syndrome
      (CTS). Cases with cervical radiculopathy and polyneuropathy as well as patients
      with ulnar nerve entrapment at elbow were excluded from the study. Fifty-three
      cases (46 females, seven males) whose ages ranged between 20 and 72 years (mean:
      49.31 +/- 13.78) were evaluated. Among 53 cases, 12 (22.6%) bilateral and 41
      (77.3%) unilateral CTS were detected. Totally 65 wrists evaluated and
      prolongation of median nerve wrist-3rd digit distal sensory latencies (DSL; N:
      59; 90.7%) and wrist-abductor pollicis brevis distal motor latencies (N: 48;
      73.8%) were seen. In six wrists, diagnoses were established with the detection of
      an increase in the differences between wrist-4th digit DSL of median and ulnar
      nerve. This test was used if other test results were in normal limits.
      Prolongation of ulnar nerve wrist-5th digit DSL were found in 12 wrists (18.4%)
      in cases with CTS. Among these 12 wrists mild (N: 2), moderate (N: 7) and severe
      (N: 3) CTS were detected. Ulnar nerve motor conduction studies provided normal
      results. In conclusion, we are in the opinion that for the detection of
      associated ulnar nerve wrist entrapments, ulnar nerve conduction studies paying
      special attention to DSL convey importance in established cases with CTS.

PMID- 14672823
TI  - Distal hypoglycemic neuropathy. An insulinoma-associated case, misdiagnosed as
      temporal lobe epilepsy.
AB  - Peripheral distal neuropathy associated with hypoglycemia secondary to insulinoma
      is quite rare. So far, less than 40 cases have been reported in literature. In
      this report, we describe a 50-year-old patient with insulinoma-polineuropathy and
      neuropsychiatric symptoms, interpreted as temporal lobe epilepsy, over the
      preceding 7 years. Due to the variability of the clinical presentation,
      diagnostic mistakes are frequent, and diagnosis of insulinoma is often delayed.
      Thus, the hypoglycemic nature of neuropathy can be lately recognized.

PMID- 14672825
TI  - Inhibition of pathogens on fresh produce by ultraviolet energy.
AB  - Ultraviolet energy at a wavelength of 253.7 nm (UVC) was investigated for its
      bactericidal effects on the surface of Red Delicious apples, leaf lettuce and
      tomatoes inoculated with cultures of Salmonella spp. or Escherichia coli O157:H7.
      Inoculated samples were subjected to different doses ranging from 1.5 to 24
      mW/cm(2) of UVC and enumerated on tryptic soy agar plus 0.05 g/l nalidixic acid
      to determine effective log reductions of microbial populations. UVC applied to
      apples inoculated with E. coli O157:H7 resulted in the highest log reduction of
      approximately 3.3 logs at 24 mW/cm(2). Lower log reductions were seen on tomatoes
      inoculated with Salmonella spp. (2.19 logs) and green leaf lettuce inoculated
      with both Salmonella spp. and E. coli O157:H7 (2.65 and 2.79, respectively). No
      significant statistical difference (p>0.05) was seen in the ability of UVC to
      inactivate a higher population of either Salmonella spp. or E. coli O157:H7 on
      the surface of green leaf lettuce. No significant difference was seen among the
      use of different doses applied to the surface of fresh produce for reduction of
      E. coli O157:H7 or Salmonella spp. (p>0.05). The use of UVC may prove to be
      beneficial in protecting the safety of fruits and vegetables in conjunction with
      Good Agricultural Practices and Good Manufacturing Practices.

PMID- 14672826
TI  - Lactobacillus casei, dominant species in naturally fermented Sicilian green
      olives.
AB  - This study investigated the phenotypic and genotypic characteristics of lactic
      acid bacteria in naturally fermented green olives, collected from different areas
      of Sicily. Both classical biochemical tests and PCR/Restriction Fragments Length
      Polymorphism (RFLP) of 16S rDNA were used to characterize the isolates. The
      identity of the isolates was obtained by the partial sequencing analysis of the
      16S rDNA. The BioMerieux software assigned the 13 heterofermentative strains to
      the Lactobacillus brevis species; 24 homofermentative strains were classified as
      Lactobacillus casei and the remaining 11 homofermentative lactobacilli were
      identified as Lactobacillus plantarum. The rapid ID 32 STREP test identified
      coccal-shaped strains as Enterococcus faecium species. The PCR/RFLP analysis
      showed a remarkable bacterial heterogeneity within the isolates. The 16S rDNA
      partial sequencing did not confirm biochemical identification, revealing a strong
      dominance of isolates belonging to the L. casei species. It is noteworthy that
      this species has never been reported as dominant species in fermented
      vegetables.A combination of molecular and biochemical analysis allowed the
      identification of species involved in natural food fermentations.

PMID- 14672827
TI  - Effective control of Listeria monocytogenes by combination of nisin formulated
      and slowly released into a broth system.
AB  - In order to identify conditions for efficient food preservation by nisin, the
      sensitivity of Listeria monocytogenes to this preservative was studied under the
      following three model conditions: (1) the instantaneous addition of nisin into
      broth medium to simulate the formation of nisin in foods, (2) the slow delivery
      of nisin solution into broth medium using a pump to simulate the slow release of
      nisin from packaging materials to foods, (3) a combination of the two delivery
      methods. Based on the following results, we conclude that the antimicrobial
      effectiveness of nisin strongly depends on its mode of delivery. The
      instantaneous and slow methods for adding nisin inhibited L. monocytogenes, but
      over time of exposure, L. monocytogenes developed tolerance to nisin. Our data
      indicate that cells treated with instantaneously added nisin developed resistance
      to higher concentrations of nisin (200 IU/ml), compared to cells treated with
      slowly added nisin at the same total amount of the antimicrobial. Further studies
      indicated that nisin-tolerant cells recovered from treatments in which 200 IU/ml
      nisin was added instantaneously were likely to be mutants, which became resistant
      to the bacteriocin. In contrast, when 200 IU/ml of the antimicrobial was added
      slowly to the cells, only a temporary tolerance was developed; these cells became
      nisin-sensitive after passage through nisin-free medium. Due to the development
      of nisin-resistant cells, excessive amounts of nisin in the model system did not
      further inhibit L. monocytogenes. These results signify that excess nisin in
      foods does not necessarily improve the efficiency of controlling L.
      monocytogenes. Our data suggest that the combination of packaging material
      containing nisin used in conjunction with nisin-containing foods will provide the
      most effective means of preventing L. monocytogenes growth.

PMID- 14672828
TI  - Foodborne viruses: an emerging problem.
AB  - Several groups of viruses may infect persons after ingestion and then are shed
      via stool. Of these, the norovirus (NoV) and hepatitis A virus (HAV) are
      currently recognised as the most important human foodborne pathogens with regard
      to the number of outbreaks and people affected in the Western world. NoV and HAV
      are highly infectious and may lead to widespread outbreaks. The clinical
      manifestation of NoV infection, however, is relatively mild. Asymptomatic
      infections are common and may contribute to the spread of the infection.
      Introduction of NoV in a community or population (a seeding event) may be
      followed by additional spread because of the highly infectious nature of NoV,
      resulting in a great number of secondary infections (50% of contacts). Hepatitis
      A is an increasing problem because of the decrease in immunity of populations in
      countries with high standards of hygiene. Molecular-based methods can detect
      viruses in shellfish but are not yet available for other foods. The applicability
      of the methods currently available for monitoring foods for viral contamination
      is unknown. No consistent correlation has been found between the presence of
      indicator microorganisms (i.e. bacteriophages, E. coli) and viruses. NoV and HAV
      are highly infectious and exhibit variable levels of resistance to heat and
      disinfection agents. However, they are both inactivated at 100 degrees C. No
      validated model virus or model system is available for studies of inactivation of
      NoV, although investigations could make use of structurally similar viruses (i.e.
      canine and feline caliciviruses). In the absence of a model virus or model
      system, food safety guidelines need to be based on studies that have been
      performed with the most resistant enteric RNA viruses (i.e. HAV, for which a
      model system does exist) and also with bacteriophages (for water). Most
      documented foodborne viral outbreaks can be traced to food that has been manually
      handled by an infected foodhandler, rather than to industrially processed foods.
      The viral contamination of food can occur anywhere in the process from farm to
      fork, but most foodborne viral infections can be traced back to infected persons
      who handle food that is not heated or otherwise treated afterwards. Therefore,
      emphasis should be on stringent personal hygiene during preparation. If viruses
      are present in food preprocessing, residual viral infectivity may be present
      after some industrial processes. Therefore, it is key that sufficient attention
      be given to good agriculture practice (GAP) and good manufacturing practice (GMP)
      to avoid introduction of viruses onto the raw material and into the food
      manufacturing environment, and to HACCP to assure adequate management of (control
      over) viruses present during the manufacturing process. If viruses are present in
      foods after processing, they remain infectious in most circumstances and in most
      foods for several days or weeks, especially if kept cooled (at 4 degrees C).
      Therefore, emphasis should be on stringent personal hygiene during preparation.
      For the control of foodborne viral infections, it is necessary to: Heighten
      awareness about the presence and spread of these viruses by foodhandlers;
      Optimise and standardise methods for the detection of foodborne viruses; Develop
      laboratory-based surveillance to detect large, common-source outbreaks at an
      early stage; and Emphasise consideration of viruses in setting up food safety
      quality control and management systems (GHP, GMP, HACCP).

PMID- 14672829
TI  - Antagonistic activities of several bacteria on in vitro growth of 10 strains of
      Campylobacter jejuni/coli.
AB  - Chicken meat contaminated with Campylobacter jejuni can be the source of human
      enteritis. To decrease the risk of human infection, Campylobacter should be
      controlled at farm levels. Orally given probiotic bacteria could prevent
      colonisation of chicken with pathogenic bacteria like Campylobacter. The aim of
      this study was to investigate the effect of different bacteria on Campylobacter
      growth. Our results demonstrated that bacteria isolated from conventional chicken
      had potential inhibitory activities against Campylobacter. Other bacteria not
      isolated from chickens but with known antagonistic capacities, e.g. Enterococcus
      (56 strains) and Escherichia coli (20 strains), did not show any negative effect
      on Campylobacter. Interestingly, one Lactobacillus (P93) strain isolated from the
      chicken gut showed bactericidal activity against all tested Campylobacter. The
      bactericidal effect was characterised as the production of organic acids in
      combination with probably production of an anti-Campylobacter protein. In a co
      culture study of Campylobacter and Lactobacillus (P93), the culturability of
      Campylobacter was under the detection limit after 48 h of incubation. A chicken
      experiment is needed to further evaluate the effect of the promising probiotic
      bacteria against Campylobacter colonisation in chicken.

PMID- 14672830
TI  - Survival of acid-adapted or nonadapted Escherichia coli O157:H7 in apple wounds
      and surrounding tissue following chemical treatments and storage.
AB  - This study evaluated survival/growth of acid-adapted or nonadapted Escherichia
      coli O157:H7 inoculated (4 log CFU/wound) in wounds (10 mm deepx6 mm diameter) of
      apples. Wounds were inoculated with a green fluorescent protein (GFP)-expressing
      derivative of a rifampicin-resistant strain of E. coli O157:H7 ATCC 43895 and
      allowed to attach (1 h). Apples were dipped (2 min) in solutions (approximately
      25 degrees C) of water (W), 5% acetic acid (AA), 5% hydrogen peroxide (HP), 0.02%
      sodium hypochlorite (SH), or not treated (NT), and stored at 25 degrees C.
      Survivors were determined in cores (10-mm deep) of the apple wounds (12 mm from
      center of wound; inner core) and surrounding tissue (18 mm from center of wound;
      outer core) after homogenizing the samples in Dey-Engley (D/E) neutralizing broth
      and plating on tryptic soy agar (TSA) and TSA supplemented with 100 microg/ml
      rifampicin (35 degrees C, 48 h) after 0, 2 and 5 days. Average bacterial
      populations at day-0 were 4.0 and 2.0 logs in the inner and outer core,
      respectively. In the inner core of the untreated apples populations increased to
      7.0 logs at day-2, while counts did not exceed 3.0 logs in the outer core during
      storage of all treatments. Previous acid-adaptation of the cultures did not
      affect survival of the pathogen. Dipping in W, AA and SH did not reduce initial
      bacterial populations, while at day-2 of storage inner core counts from W, AA and
      SH reached 7.1, 5.5 and 6.9 logs, respectively. In contrast, HP reduced initial
      counts in the inner core by approximately 1.5 logs, but they increased to 7.0
      logs by day-2. Populations of all treatments reached 6.6-7.2 logs in the inner
      core by day-5. Thus, sanitizer treatment did not effectively reduce nor inhibit
      growth of E. coli O157:H7 contamination in apple wounds and surrounding tissue.

PMID- 14672831
TI  - Enhancement of nisin, lysozyme, and monolaurin antimicrobial activities by
      ethylenediaminetetraacetic acid and lactoferrin.
AB  - A microtiter plate assay was employed to systematically assess the interaction
      between ethylenediaminetetraacetic acid (EDTA) or lactoferrin and nisin,
      lysozyme, or monolaurin against strains of Listeria monocytogenes, Escherichia
      coli, Salmonella enteritidis, and Pseudomonas fluorescens. Low levels of EDTA
      acted synergistically with nisin and lysozyme against L. monocytogenes but EDTA
      and monolaurin interacted additively against this microorganism. EDTA
      synergistically enhanced the activity of nisin, monolaurin, and lysozyme in
      tryptic soy broth (TSB) against two enterohemorrhagic E. coli strains. In
      addition, various combinations of nisin, lysozyme, and monolaurin with EDTA were
      bactericidal to some gram-negative bacteria whereas none of the antimicrobials
      alone were bactericidal. Lactoferrin alone (2000 microg ml(-1)) did not inhibit
      any of the bacterial strains, but did enhance nisin activity against both L.
      monocytogenes strains. Lactoferrin in combination with monolaurin inhibited
      growth of E. coli O157:H7 but not E. coli O104:H21. While lactoferrin combined
      with nisin or monolaurin did not completely inhibit growth of the gram-negative
      bacteria, there was some growth inhibition. All combinations of EDTA or
      lactoferrin with antimicrobials were less effective in 2% fat UHT milk than in
      TSB. S. enteritidis and P. fluorescens strains were consistently more resistant
      to antimicrobial combinations. Resistance may be due to differences in the outer
      membrane and/or LPS structure.

PMID- 14672832
TI  - Effect of water activity and temperature on competing abilities of common
      postharvest citrus fungi.
AB  - The effect of temperature (4-30 degrees C) and water activity (a(w), 0.995-0.90)
      on the 'in vitro' interactions between Penicillium digitatum, Penicillium
      italicum and Geotrichum candidum were evaluated. The effect of temperature on
      growth of green and blue mould decays and their interactions on wounded oranges
      was also studied. The major competing abilities were observed at optimal
      conditions of temperature and a(w) for growth (25 degrees C and 0.995 a(w)), and
      no differences between growth rates when the fungi were growing alone or paired
      were observed in the other studied conditions. P. italicum and G. candidum were
      able to reduce the growth rate of P. digitatum when it was growing paired 'in
      vitro', suggesting that inhibitory metabolites were produced. In the 'in vivo'
      assays, growth rates of green mould were higher than those of blue mould at any
      temperature studied. However, at 4 degrees C, P. italicum began its rot
      development 1 week before P. digitatum. When these two pathogens were inoculated
      into the same wound at 25 degrees C, blue mould was practically inhibited. The
      difference between the results obtained in 'in vitro' and 'in vivo' assays
      suggests that other factors could interact with fungi, favoring the development
      of one pathogen to the detriment of the others.

PMID- 14672833
TI  - The late blowing in cheese: a new molecular approach based on PCR and DGGE to
      study the microbial ecology of the alteration process.
AB  - A molecular biology method based on polymerase chain reaction (PCR) and
      denaturing gradient gel electrophoresis (DGGE) was developed to detect
      Clostridium spp. in cheese samples suspected of late blowing. Strains of
      Clostridium spp. and different Lactic Acid Bacteria species, obtained from
      international collections, were used to determine the experimental conditions for
      the PCR amplification and DGGE differentiation. DNA extracted directly from
      cheeses with late blowing symptoms was subjected to PCR and DGGE analysis and
      traditional agar plating was performed for samples pasteurized and enriched
      overnight. Moreover, volatile fatty acids were determined for comparison
      purposes. The PCR-DGGE results were in agreement with the plating performed, and
      only samples presenting DGGE bands migrating at the same position as Clostridium
      spp. bands, showed the presence of Clostridium colonies on Reinforced Clostridial
      Medium plates. Butyric acid contents were high (>100 mg/kg) in the cases of
      positive DGGE results, underlining the suitability of the protocol for the study
      of cheese spoilage. The sensitivity of the method is estimated to be 10(4) CFU/g.

PMID- 14672834
TI  - The lactobin A and amylovorin L471 encoding genes are identical, and their
      distribution seems to be restricted to the species Lactobacillus amylovorus that
      is of interest for cereal fermentations.
AB  - Lactobin A and amylovorin L471 are two bacteriocins produced by the
      phenotypically different strains Lactobacillus amylovorus LMG P-13139 and L.
      amylovorus DCE 471, respectively. A 110-bp PCR fragment of the structural gene of
      lactobin A was obtained from total genomic DNA of L. amylovorus LMG P-13139,
      which was used as a probe to isolate a 3.6-kb HindIII chromosomal fragment for
      sequencing. PCR amplification revealed that both the structural genes of both the
      bacteriocins lactobin A and amylovorin L471 were identical. These bacteriocins
      will be further referred to as amylovorin L. Amylovorin L can be defined as a
      small, strongly hydrophobic, antibacterial peptide consisting of 50 amino acids.
      It is synthesized as a precursor peptide of 65 amino acids processed at a
      characteristic double-glycine proteolytic cleavage site. Amylovorin L hence
      belongs to the class II bacteriocins. It has a narrow inhibitory spectrum, being
      most active towards Lactobacillus delbrueckii subsp. bulgaricus LMG 6901(T).
      Among 38 strains of the Lactobacillus acidophilus DNA homology group, another 6
      L. amylovorus strains were also inhibitory towards the L. delbrueckii subsp.
      bulgaricus LMG 6901(T) strain. The lactobin A or amylovorin L471 structural genes
      could be detected in the genomes of three of these L. amylovorus strains, but
      only after extensive PCR amplification, indicating that the inhibitory substances
      were slightly different. The bacteriocins were characterized as small
      (approximately 4800 Da), heat-stable peptides that were active in a wide pH range
      (2.2-8.0). Finally, preliminary experiments indicated that the production of
      amylovorin L by L. amylovorus DCE 471 took place during a natural rye
      fermentation, indicating its potential importance in the development of a
      functional (probiotic) starter culture for cereal fermentations.

PMID- 14672835
TI  - Growth of Salmonella enteritidis in yolk from eggs laid by immunized hens.
AB  - After hyperimmunization of laying hens with Salmonella enteritidis, antibodies
      can be found in egg yolks. This study was conducted to ascertain whether the
      growth of S. enteritidis would be suppressed in the presence of antibodies
      contained in egg yolk. Specifically pathogen-free (SPF)-laying hens were
      immunized with S. enteritidis; eggs were collected, the yolk was separated and
      the concentration of S. enteritidis antibodies was determined quantitatively by
      using the enzyme-linked immunosorbent assay (ELISA), the radial immunodiffusion
      and the bicinchoninic acid protein assay. Then, the yolk was inoculated with
      approximately 10, 100 or 1000 S. enteritidis cells/ml and incubated at 15, 20 and
      30 degrees C for 0, 2, 6 and 24 h. The growth of organisms in each yolk was
      examined, and the generation times were calculated. The egg yolk from
      nonimmunized hens served as negative control. The highest level of antibody
      concentration was found in the hyperimmunized group. There was no difference in
      the generation times of S. enteritidis between the antibody-positive yolk and the
      negative yolk at the three different incubation temperatures. The results suggest
      that antibodies in the yolk do not influence the growth of S. enteritidis, even
      if the hens are highly immunized.

PMID- 14672840
TI  - Flocculation in mixtures of cationic polyelectrolytes and anionic surfactants.
AB  - The phase behavior of mixtures of a cationic polyelectrolyte ('Jaguar') and an
      anionic surfactant (either sodium dodecyl sulfate or sodium lauryl ether sulfate)
      has been studied. For a given polyelectrolyte (and added NaCl) concentration,
      with increasing surfactant concentration, three phase regions were identified.
      The first region is a single homogeneous phase. Within this region, at some
      surfactant concentration, above the critical aggregation concentration, stable
      open-network 'particles' form, typically approximately 100 nm in size, which are
      net positively charged. However, as the surfactant concentration is increased
      further, these particles aggregate and form a two-phase system, i.e. a separated
      gel phase, containing a high percentage of water, co-existing with an aqueous
      surfactant phase. At some higher surfactant concentration still, the particles
      become sufficiently negatively charged that they re-stabilize. Beyond this
      surfactant concentration, therefore, the system reverts to being a single,
      homogeneous phase. Within the two-phase (aggregated particle) region an iso
      electric point for the particles has been observed at a certain surfactant
      concentration, by electrophoresis. Furthermore, in this aggregated, gel-phase
      region, there appear to be typically approximately 2-4 surfactant molecules
      associated with each cationic site of the polymer chains. It is postulated that
      association of the anionic surfactant molecules occurs within the polyelectrolyte
      chains, binding them together, to form the particles referred to. These
      associated surfactant structures have been referred to here as 'internal'
      micelles. A crude estimate has been made, based on turbidity/time measurements,
      that there may be up to approximately 1000 polymer chains in each primary
      particle, bound together by the internal surfactant micelles. Small-angle light
      scattering studies of the aggregating particles indicate a fractal dimension for
      the aggregates, which would correspond to a diffusion-limited aggregation
      process.

PMID- 14672841
TI  - The importance of the interfacial stabilising layer on the macroscopic flow
      properties of suspensions dispersed in non-adsorbing polymer solution.
AB  - In this paper, the rheological properties, microscopic appearance and macroscopic
      sedimentation behaviour of 147- and 482-nm polystyrene latices in HEC solutions,
      bearing different adsorbed poly(ethyleneoxide)-poly(propyleneoxide)
      poly(ethyleneoxide) (PEO-PPO-PEO) copolymers are presented and compared with
      previous results with a 67-nm latex (Langmuir 13 (1997) 2922). The ratio of the
      steric layer thickness to the particle radius varies from 1:5 to 1:40 for the
      three latex sizes covering a range of particle softness. The 147-nm latex showed
      gas, liquid and solid phases, including three phase coexistence with increasing
      concentrations of HEC. The solid phase was a viscoelastic gel that sedimented
      slowly and showed initially slow, then faster sedimentation rates for HEC
      concentrations close to the fluid-gel phase boundary. These properties depended
      on the adsorbed PEO-PPO-PEO copolymers; the fluid-gel phase boundary moved to
      lower HEC concentrations with increasing PEO chain length. Oscillatory shear
      measurements were sensitive to the floc network structure and showed the
      transition from the fluid to gel phases. The values for the elastic modulus in
      the gel region were independent of the PEO chain length in the stabilizer
      implying the presence of similar floc structures with each of the different PEO
      PPO-PEO copolymers. Stress relaxation measurements gave long relaxation times (>
      10(3) s) and showed that the suspensions were viscoelastic fluids with high zero
      shear viscosities. Higher values were obtained with longer PEO chain lengths.
      Extrapolated yield stress values showed stronger flocculation with increasing PEO
      chain length in the adsorbed stabilising layer. There was good correlation
      between the extrapolated yield stress and the sedimentation velocity, indicating
      that the collapse of the floc network is governed by the strength of the inter
      particle bonds (for the same floc structure) and also with the long-time
      behaviour from the stress relaxation measurements. With the 482-nm latex there
      was less effect of the adsorbed copolymer both for the rheology and sedimentation
      behaviour, with the particles behaving more like hard spheres. The transition
      between hard and soft sphere behaviour, interpreted here as the ratio of the
      steric layer thickness to the particle radius at which the adsorbed stabilising
      layer starts to have an effect on the rheology and phase behaviour is estimated
      to be approximately 1:20.

PMID- 14672842
TI  - Review of the measurement of zeta potentials in concentrated aqueous suspensions
      using electroacoustics.
AB  - This paper reviews the technique of electroacoustics as it has been applied to
      aqueous suspensions of inorganic particles. It starts by charting the development
      of the technique from its earliest beginnings in the 1930s to the present day.
      The technique has become well established in the last decade with the advent of
      the Acoustosizer and the Acoustosizer II. Illustrations of how the technique can
      be used are given based on the author's own experience, especially the
      measurement of iso electric points, the adsorption of polyelectrolytes, the
      effect of ionic strength, the effect of powder surface area and the dissolution
      of material from powders. Some new data on (a) the adsorption of different
      molecular weights of polyacrylic acid onto alumina and (b) titanium dioxide
      suspensions are also presented.

PMID- 14672843
TI  - Recent advances in agrochemical formulation.
AB  - This review will describe some of the changes occurring in formulation types
      employed and the further trends that are driving technologies. These will be
      illustrated by examples of water-based dispersion formulation technology for oil
      in-water emulsions (EW) and suspension-emulsions (SE) as well as other
      formulation types such as emulsifiable gel and dry product formulations where new
      techniques of formulation, often combining polymers and surfactants in novel ways
      have resulted in significant formulation and sometimes processing improvements.

PMID- 14672844
TI  - Liquid crystals and microemulsions formed by mixtures of a non-ionic surfactant
      with palm oil and its derivatives.
AB  - The phase behaviour of palm olein (PO) and its derivative oils (palm oil methyl
      esters and medium chain triglycerides) with Imbentin coco 6.9EO, an ethoxylated
      C12-14 alcohol, in water has been investigated to identify compositions where
      microemulsions occur. The techniques used were the optical microscope phase
      penetration scan and small angle X-ray diffraction (SAXS). Mixed surfactant/oil
      samples were prepared at wt. ratios of 0.1:1, 0.25:1, 0.5:1 and 1:1 for the phase
      penetration scan. For SAXS analysis, the initial concentration of surfactant in
      water (W) was fixed at 38% (w/w), which forms a hexagonal mesophase (H1). Palm
      oil methyl esters (POME) and medium chain triglycerides (MCT) were added to this
      at 0.04:1 (or 0.05:1 for MCT), 0.1:1, 0.2:1 (or 0.25:1 for MCT), 0.5:1 and 1:1
      ratios of oil to surfactant. Schematic phase diagrams were constructed to
      document the changes of phase structures using both bulk samples and phase
      penetration scans techniques. The extent of microemulsion formation (or
      solubilisation) decreases in the sequence POME > MCT > PO, and increases
      substantially with temperature, particularly for POME and MCT. All of the oils
      destabilize the hexagonal phase; for POME and MCT there is an increase in the
      surfactant cloud point temperature by ca. 10 degrees C or more, but the
      temperature for the onset of the lamellar (Lalpha) phase dispersion region (W +
      Lalpha) is hardly affected. There was a pronounced tendency for the lamellar
      phase formed in the presence of high oil concentrations and low water levels to
      have a reduced melting point. With the highest MCT levels a bicontinuous cubic
      phase (probably V2) is present at 25 degrees C, although this phase is not
      present in the binary surfactant/water system. The X-ray diffraction results show
      that the average area per head group (ao) at the micelle surface is decreased by
      the addition of the oils, consistent with the observation of a V2 phase. Possible
      molecular mechanisms for this observation are discussed.

PMID- 14672845
TI  - Formation and properties of mini-emulsions formed by microemulsions dilution.
AB  - Mini-emulsions have been formed in quaternary systems water/hexanol/sodium
      dodecyl sulfate/decane by dilution of a microemulsion with an excess of water. We
      have investigated systematically the effect of composition variables in the
      droplet size and Ostwald Ripening rate. This droplet size has been investigated
      by using dynamic light scattering of samples submitted to further dilution in
      water. According to the dynamic light scattering results, the initial droplet
      size depends on the initial microemulsion water content, the larger the initial
      water concentration, the smaller the initial droplet size. This is probably
      related to the structure of the initial phase. The rate of Ostwald Ripening
      depends on the final surfactant concentration as expected for differences in
      interfacial tension. At high surfactant and dispersed phase contents, instability
      due to flocculation has been observed. Other experiments in which a fifth
      component (a more hydrophobic oil) was added to slow down Ostwald Ripening showed
      an initial droplet size increasing comparable to the systems without additive but
      after a relatively long time of approximately 2 h, a decrease was observed.

PMID- 14672846
TI  - Rational design and engineering of delivery systems for therapeutics: biomedical
      exercises in colloid and surface science.
AB  - Engineering delivery systems of therapeutic agents has grown into an independent
      field, transcending the scope of traditional disciplines and capturing the
      interest of both academic and industrial research. At the same time, the
      acceleration in the discovery of new therapeutic moieties (chemical, biological,
      genetic and radiological) has led to an increasing demand for delivery systems
      capable of protecting, transporting, and selectively depositing those therapeutic
      agents to desired sites. The vast majority of delivery systems physically reside
      in the colloidal domain, while their surface properties and interfacial
      interactions with the biological milieu critically determine the pharmacological
      profiles of the delivered therapeutic agents. Interestingly though, the colloidal
      and surface properties of delivery systems are commonly overlooked in view of the
      predominant attention placed on the therapeutic effectiveness achieved. Moreover,
      the development and evaluation of novel delivery systems towards clinical use is
      often progressed by serendipity rather than a systematic design process, often
      leading to failure. The present article will attempt to illustrate the colloid
      and interfacial perspective of a delivery event, as well as exemplify the vast
      opportunities offered by treating, analysing and manipulating delivery systems as
      colloidal systems. Exploring and defining the colloid and surface nature of the
      interactions taking place between the biological moieties in the body and an
      administered delivery vehicle will allow for the rational engineering of
      effective delivery systems. A design scheme is also proposed on the way in which
      the engineering of advanced delivery systems should be practiced towards their
      transformation from laboratory inventions to clinically viable therapeutics.
      Lastly, three case studies are presented, demonstrating how rational manipulation
      of the colloidal and surface properties of delivery systems can lead to newly
      engineered systems relevant to chemotherapy, gene therapy and radiotherapy.

PMID- 14672847
TI  - The use of surface-active agents in the preparation and assembly of quantum-sized
      nanoparticles.
AB  - This overview summarises the use of surface-active agents for preparation of
      nanoparticles. It starts with description of the nanotechnology vision.
      Nanoparticle products are exemplified by using solid-state processes, e.g. for
      the production of ceramics or catalysts, as well as colloidal processes whereby
      the use of surface-active agents plays a major role. Several examples are given
      in the review, e.g. use of coordination ligands and nanoparticle self-assembly.
      The process of control of nanoparticle shape and its modulation is briefly
      described and examples are given to demonstrate such control.

PMID- 14672848
TI  - The spreading of surfactant solutions on thin liquid films.
AB  - The spreading of a surfactant solution on a water film at first glance seems a
      trivial problem. However, in the last 30 years or so this has been shown to be
      anything like the case. There have been numerous studies which show that
      Marongoni driven fingering of the spreading surfactant front exists. In this
      paper this work has been reviewed and an attempt has been made to rationalise the
      results. The paper concludes with some recent observations of ours concerning the
      spreading of sodium dodecyl sulfate over relatively thick water films, 200 microm
      or less.

PMID- 14672849
TI  - Description of the adsorption behaviour of proteins at water/fluid interfaces in
      the framework of a two-dimensional solution model.
AB  - In the framework of the two-dimensional non-ideal solution model, surface layer
      equations of state, adsorption isotherms and functions of the distribution of
      protein molecules in respect to different molar area were derived. The
      thermodynamic analysis was based on Butler's equation for the chemical potentials
      of the components and a first-order model for the non-ideality of surface layer
      enthalpy and entropy. For concentrated solutions, aggregation of protein
      molecules in the surface layer was assumed. The resulting equations
      satisfactorily describe the measured adsorption and surface pressure isotherms of
      proteins at liquid/fluid interfaces in terms of a set of constant parameters. The
      model reflects the well-known differences between proteins and ordinary
      surfactants: a sharp increase in the surface pressure with concentration beyond a
      certain protein adsorption; an almost constant surface pressure at higher
      concentrations and a significant increase in the adsorption layer thickness with
      increasing adsorption for flexible proteins.

PMID- 14672850
TI  - Ostwald ripening in emulsions: estimation of solution thermodynamics of the
      disperse phase.
AB  - The rate of Ostwald ripening has been measured for small emulsions prepared by
      the dilution of O/W microemulsions containing a range of n-alkanes. The rates
      were determined as a function of temperature for decane, undecane, dodecane and
      tri-decane using photon correlation spectroscopy. The aqueous solubilities of
      these oils were estimated from the rates of ripening using the Lifshitz, Slyozov
      and Wagner theory of Ostwald ripening. These solubilities were used to calculate
      the free energy, enthalpy and entropy of solution for the 4 alkanes. Values
      obtained were in good agreement with literature values. The free energy of
      solution of hexadecane and octadecane were also determined from the rate of
      ripening of mixed oil phase emulsions with dodecane using the treatment suggested
      by Kabalnov. The values obtained agreed well with extrapolated values of the free
      energy from lower alkanes, suggesting that coiling or aggregation of the longer
      chain molecules in solution was not affecting the solubility.

PMID- 14672851
TI  - Benzimidazole drugs and modulation of biotransformation enzymes.
AB  - Benzimidazole drugs (e.g., anthelmintics albendazole, fenbendazole,
      oxfenbendazole, thiabendazole, mebendazole; inhibitors of proton pump omeprazole,
      lansoprasole, pantoprasole) represent substances used in both human and
      veterinary medicine; however, from the point of view of induction and inhibition
      of biotransformation enzymes, research has been carried out mainly due to the
      initiative of human pharmacologists. The purpose of the present review is to
      inform about inductive and inhibitive effects of benzimidazole drugs in man,
      animals and cell cultures. Pharmacological and toxicological consequences of
      modulation of biotransformation enzymes are discussed and the significance of
      studies in the field of modulation of biotransformation enzymes in food-producing
      animals is explained. Since the modulating effect of benzimidazoles strongly
      varies depending on structure of the individual substances, the particular
      attention is paid to structure-modulation relationships.

PMID- 14672852
TI  - Validation of a method for collection and assay of pentane in the exhaled breath
      of the horse.
AB  - Oxidative stress refers to an imbalance between the production of oxidising free
      radicals and the antioxidant defenses of the cell, and is associated with many
      pathogenic processes. Oxidative damage to cellular lipids results in the
      evolution of pentane and ethane gas, and detection of these hydrocarbons in the
      exhaled breath can be used to monitor in vivo oxidative stress. The aim of this
      study was to validate a gas chromatography (GC) method for measurement of breath
      pentane in the horse. The GC-system developed showed good specificity for
      discrimination of pentane from other breath hydrocarbons, and was sensitive to
      0.5 ppb pentane. Pentane was detected in the exhaled breath of five horses
      investigated on two occasions. The results of this preliminary study demonstrate
      that breath pentane can be measured in the horse, and further work is now
      justified to investigate the feasibility of applying this method for monitoring
      in vivo oxidative stress in the horse.

PMID- 14672854
TI  - Effect of time delay and storage temperature on blood gas and acid-base values of
      bovine venous blood.
AB  - The aim of this study was to investigate possible changes in the gas composition
      and acid-base values of bovine venous blood samples stored at different
      temperatures (+4, 22 and 37 degrees C) for up to 48 h. Five healthy cattle were
      used in the study. A total of 15 blood samples collected from the animals were
      allocated into three groups, which were, respectively, then stored in a
      refrigerator adjusted to +4 degrees C (Group I, n=5), at a room temperature of
      about 22 degrees C (Group II, n=5) and in an incubator adjusted to 37 degrees C
      (Group III; n=5) for up to 48 h. Blood gas and acid-base values were analysed at
      0 (baseline), 1, 2, 3, 4, 5, 6, 12, 24, 36 and 48 h of storage. A significant
      decrease (p<0.001) was found, in the pH of the refrigerated blood after 5 h and
      its maximum decrease was recorded at 48 h as 0.04 unit. There were also
      significant alterations (p<0.001) in the blood pH of the samples stored at room
      temperature and in the incubator after 2 and 3 h, respectively. The maximum mean
      alteration in pCO(2) value for Group I was -0.72 kPa during the assessment, while
      for groups II and III, maximum alterations in pCO(2) were detected as +2.68 and
      +4.16 kPa, respectively. Mean pO(2) values increased significantly (p<0.001) for
      Group I after 24 h and for Group II after 6 h, while a significant decrease was
      recorded for Group III after 24 h (p<0.001). Base excess (BE) and bicarbonate
      (HCO(3)) fractions decreased significantly for all the groups during the study,
      compared to their baseline values. In conclusion, acid-base values of the samples
      stored at 22 and +4 degrees C were found to be within normal range and could be
      used for clinical purposes for up to 12 and 48 h, respectively, although there
      were small statistically significant alterations.

PMID- 14672853
TI  - Determinants of weak femoral artery pulse in dogs with mitral valve prolapse.
AB  - In three substudies encompassing 247 dogs from two breeds predisposed to
      myxomatous mitral valve disease (MMVD), femoral artery pulse strength was
      palpated and related to potential explanatory factors, including quantitative
      echocardiographic measures of MMVD, aortic and femoral artery diameter and wall
      thickness and blood pressure. In addition, in 109 Cavalier King Charles Spaniels
      (of which 61 were included in the three substudies mentioned above), the relation
      between femoral artery pulse strength and presence of thrombocytopenia was
      investigated. In 26% of the dogs, a pulse </=50% of normal strength was detected;
      six dogs (2.0%) had an absent pulse unilaterally or bilaterally. Mitral valve
      prolapse severity, degree of obesity, heart rate and age all influenced femoral
      artery pulse strength negatively. Weak femoral artery pulses were not related to
      clinical signs or to decreased pulse pressure or stroke volume. A weak femoral
      artery pulse reflected reduced artery diameter and/or distension rather than
      occlusion. In conclusion, weak femoral artery pulses in dogs with MMVD seem to be
      associated with regional/local reductions in blood flow and not arteriosclerosis
      or platelet count.

PMID- 14672855
TI  - Prevalence of thyroglobulin autoantibodies detected by enzyme-linked
      immunosorbent assay of canine serum in hypothyroid, obese and healthy dogs in
      Japan.
AB  - Thyroglobulin autoantibodies (TgAA) were detected in sera of hypothyroid (n=19),
      obese (n=28) and clinically healthy dogs (n=52) using a commercially available
      immunoassay kit. TgAA-positive results occurred in 10 of 19 hypothyroid, 1 of 28
      obese and 1 of 52 clinically healthy dogs. The clinically healthy TgAA-positive
      dog had additional evidence of hypothyroidism supported by low total T(4), low
      free T(4) and high canine TSH. Among the breeds, Golden Retriever had the highest
      frequency of hypothyroid (9/19) and TgAA-positive hypothyroid dogs (6/10). This
      study was the first survey about the prevalence of canine TgAA in Japan and could
      be a useful reference for clinicians.

PMID- 14672856
TI  - Relationship between cell proliferation and tenascin-C expression in canine
      gastrointestinal tumours and normal mucosa.
AB  - Tenascin-C is an extracellular matrix glycoprotein that has been implicated in
      cell proliferation and adhesion by in vitro experiments. Its expression is known
      to be increased in canine and human gastrointestinal tumours. The aim of this
      study was to investigate the possible relationship between cell proliferation and
      tenascin expression in these tumours. In tissue sections of normal stomach, small
      intestine and colon, and gastrointestinal epithelial tumours, the monoclonal
      antibody Ki-67, which is directed against a proliferation-associated nuclear
      antigen, was used to identify proliferating cells. Serial sections were also
      stained for tenascin. Serial sections stained for tenascin and Ki-67 were
      compared to determine whether there is a correlation between tenascin expression
      and tumour cell proliferation. In the normal gastric mucosa, Ki-67 positive cells
      were confined to the neck region and in the normal small intestinal mucosa
      positive cells were confined to the lower parts of the crypts. In adenomas and
      carcinomas, the frequency of positive cells was increased at the edges of
      adenomas and invasive tumour margins of carcinomas and there was inter- and intra
      tumoural heterogeneity. Carcinomas with lymphatic invasion showed a high Ki-67
      index. There was no relation between cell proliferation and tenascin expression
      in both normal tissues and tumours studied. The absence of a correlation between
      tenascin and Ki-67 expression suggests that the main function of tenascin in both
      normal tissues and tumours of the canine gastrointestinal tract is antiadhesion
      rather than proliferation.

PMID- 14672857
TI  - Effect of high intensity training on anaerobic capacity of middle gluteal muscle
      in Thoroughbred horses.
AB  - We hypothesize that high intensity training for Thoroughbred horses that have
      been subjected to conventional training could further improve the metabolic
      properties of the middle gluteal muscle. Nine well-trained horses were subjected
      to high intensity (80-100% Vdot;O(2)max, 5 minx2) training for 12 weeks. Biopsy
      samples were obtained from the muscle before and after 4 and 12 weeks of
      training. Three of the 9 horses did not complete the training programme. In the
      remaining 6 horses, activities of succinic dehydrogenase (SDH),
      phosphofructokinase (PFK) and 3-hydroxy acyl CoA dehydrogenase (HAD), and the
      composition of myosin heavy chain isoforms were analyzed by biochemical
      techniques. After 12 weeks of training, a significant increase was found in PFK
      activity but not in the SDH and HAD activities. There were no significant changes
      in the composition of myosin heavy chain isoforms. The high intensity training in
      this study was effective at increasing glycolytic enzyme activity, indicating the
      possibility to improve anaerobic capacity, which potentially could contribute
      greatly to performance in Thoroughbred horses. This study also highlighted a fact
      that high intensity training should be given with the great care to prevent the
      skeletal muscle injuries.

PMID- 14672858
TI  - Lower gastric ulcerogenic effect of suxibuzone compared to phenylbutazone when
      administered orally to horses.
AB  - The objective was to compare the gastrointestinal and general toxicity of
      suxibuzone (SBZ) to that of phenylbutazone (PBZ) when administered orally in
      horses. Fifteen healthy horses were allocated to three treatment groups. One
      group received a high dose of PBZ for two weeks; the second group was given an
      equimolecular dosage of SBZ; and a third group received placebo. Horses were
      daily monitored, and blood samples were collected before and during the study. On
      day 18, complete post-mortem examinations were performed. One horse treated with
      PBZ showed clinical signs of NSAID toxicosis. Small oral ulcers were also
      detected in other two horses from the PBZ group and in two horses from the SBZ
      group. There were no statistical differences in the blood parameters among
      groups. Ulcers in the stomach's glandular mucosa were observed in all horses of
      the PBZ group, while only two horses of the SBZ group showed ulcerations. PBZ
      horses had a significant higher ulcerated area, and gastric ulcers were
      significantly deeper than those in the SBZ and placebo groups. No other lesions
      were found in any other tissue. In conclusion, SBZ causes significantly lower
      gastric ulcerogenic effect than PBZ when administered orally at equimolecular
      doses in horses.

PMID- 14672859
TI  - Emergence of a novel subgroup within the widely circulating lineage of foot-and
      mouth disease virus serotype Asia 1 in India.
AB  - The complete VP1 encoding (1D) gene of 54 foot-and-mouth disease (FMD) virus
      serotype Asia1 field isolates, most of which were isolated during 2000 and 2001,
      was sequenced. The phylogenetic analysis identified a novel subgroup (>10%
      nucleotide divergence) within the widely circulating lineage of this serotype.
      The newly emerged viruses were responsible for disease outbreaks in both cattle
      and buffaloes and were present in six different states in the country. Amino acid
      sequence comparison of these isolates revealed significant sequence divergence at
      many of the amino acid positions in comparison to those of lineage VI-A and C.
      Emergence of such viruses may affect the efficacy of vaccine strain currently
      used for protection against FMD in India.

PMID- 14672860
TI  - Comparative analysis on the 5'-untranslated region of bovine viral diarrhea virus
      isolated in Korea.
AB  - Samples of 249 bovine abortuses, one intestine, and four diarrheal stools from
      254 cows were collected, and bovine viral diarrhea virus (BVDV) was detected by
      reverse transcription-polymerase chain reaction (RT-PCR). Subsequently, virus
      isolation was preformed with PCR-positive samples, and then PCR product of 5(')
      untranslated region (UTR) of BVDV isolate was sequenced and analyzed. Among the
      samples collected, 20 (from 17 bovine abortuses, one intestine, and two diarrheal
      stools) were positive for BVDV RT-PCR; four BVDVs (from two bovine abortuses, one
      intestine, and one diarrheal stool) were isolated. When the four isolates were
      biotyped in cell culture, one BVDV isolate from a bovine abortus was cytopathic
      and the others were non-cytopathic. In addition, three isolates were genotyped as
      BVDV-1 and one isolate from a diarrheal stool as BVDV-2. In phylogenetic
      analysis, it suggested that the BVDV-2 isolate in Korea is closer to the North
      American strains than Asian strains. This is the first report on the
      identification and isolation of BVDV-2 in Korea.

PMID- 14672861
TI  - Lead exposure, interactions and toxicity: food for thought.
AB  - The recognition that nutritional status plays a role in altering susceptibility
      to lead absorption and toxicity has triggered the development of this review.
      There has been a significant increase worldwide in awareness and concern about
      the effects of lead on human health and the environment over the last two
      decades. Both occupational and environmental exposures to lead remain a serious
      problem in many developing and industrialising countries, as well as in some
      developed countries. Port Pirie (South Australia) has the world's largest lead
      smelter and the surrounding population continues to be exposed to environmental
      lead. The increased awareness of the detrimental impacts of 100 years of smelting
      at Port Pirie led in 1984 to the development of the Lead Implementation Program,
      run by the Environmental Health Centre (EHC), Department of Human Services (DHS).
      The major focus of the program is to reduce household lead exposure for pregnant
      women and children below the age of five years. Despite intervention efforts by
      all stakeholders in Port Pirie, 55% of children less than 4 years old have blood
      lead levels above the National Health and Medical Research Council (NH&MRC) goal
      of 10 microg/dl. The Port Pirie Lead Implementation Program includes components
      on nutrition education aimed at reducing lead absorption and toxicity. However,
      nutritional intake and nutritional status of Port Pirie residents, in particular
      children under five years, has not been evaluated. This review focuses on
      nutrition as a component of intervention in lead toxicity and it discusses the
      nutritional concerns in relation to lead exposure. Fortunately most food patterns
      that reduce susceptibility to lead toxicity are consistent with recommendations
      for a healthy diet. The relationship between nutritional status and lead uptake
      and toxicity is most clearly established for irregular food intake (i.e. periods
      of fasting), marginal calcium ingestion and (subtle) iron deficiency.

PMID- 14672862
TI  - Low-carbohydrate diets: what are the potential short- and long-term health
      implications?
AB  - Low-carbohydrate diets for weight loss are receiving a lot of attention of late.
      Reasons for this interest include a plethora of low-carbohydrate diet books, the
      over-sensationalism of these diets in the media and by celebrities, and the
      promotion of these diets in fitness centres and health clubs. The re-emergence of
      low-carbohydrate diets into the spotlight has lead many people in the general
      public to question whether carbohydrates are inherently 'bad' and should be
      limited in the diet. Although low-carbohydrate diets were popular in the 1970s
      they have resurged again yet little scientific fact into the true nature of how
      these diets work or, more importantly, any potential for serious long-term health
      risks in adopting this dieting practice appear to have reached the mainstream
      literature. Evidence abounds that low-carbohydrate diets present no significant
      advantage over more traditional energy-restricted, nutritionally balanced diets
      both in terms of weight loss and weight maintenance. Studies examining the
      efficacy of using low-carbohydrate diets for long-term weight loss are few in
      number, however few positive benefits exist to promote the adoption of
      carbohydrate restriction as a realistic, and more importantly, safe means of
      dieting. While short-term carbohydrate restriction over a period of a week can
      result in a significant loss of weight (albeit mostly from water and glycogen
      stores), of serious concern is what potential exists for the following of this
      type of eating plan for longer periods of months to years. Complications such as
      heart arrhythmias, cardiac contractile function impairment, sudden death,
      osteoporosis, kidney damage, increased cancer risk, impairment of physical
      activity and lipid abnormalities can all be linked to long-term restriction of
      carbohydrates in the diet. The need to further explore and communicate the
      untoward side-effects of low-carbohydrate diets should be an important public
      health message from nutrition professionals.

PMID- 14672863
TI  - In an era of economic growth, is inequity holding back reductions in child
      malnutrition in Vietnam?
AB  - In the past decade of economic growth, Vietnam has achieved an impressive rate of
      socioeconomic development. However, the rate of improvement in child malnutrition
      lags far behind that of most other health indicators. This study examines factors
      other than income that might affect this inability to reduce rapidly child
      malnutrition by exploring the socioeconomic factors that explain the high rates
      of stunting and underweight status of many Vietnamese children. A nationally
      representative survey of Vietnamese households, the 1997-98 Vietnam Living
      Standards Survey (VLSS) is used. Multivariate logit is used for regression
      analysis. The key parameters are household poverty status, total expenditure
      level, rural residence, and minority status with controls for many key socio
      demographic measures. Children from rural households, poor households, and ethnic
      minority backgrounds are significantly more likely to be malnourished (with a
      17.6%, 10.9%, and 14.1%, respectively, greater prevalence of malnutrition) than
      are urban residents, non-poor households, and the majority Kinh population. These
      results suggest that economic improvements in Vietnam have, for the most part,
      bypassed the rural poor and minorities and that targeting economic resources
      towards these groups will be most critical for reducing undernutrition in
      Vietnam.

PMID- 14672864
TI  - Obesity, abdominal obesity, and clustering of cardiovascular risk factors in
      South Korea.
AB  - The aim of this study was first, to investigate the prevalence of obesity,
      abdominal obesity, and clustering of cardiovascular (CVD) risk factors, and
      secondly, to identify the BMI or waist circumference (WC) level at which
      clustering increases in South Koreans. A population-based, cross-sectional
      National Health Examination Survey was carried out in 1998. A total of 8,816
      subjects (4,029 men and 4,787 women) aged 15-79 y were selected by stratified
      multistage probability sampling design. The measurements taken of the subjects
      included: height, weight, waist and hip circumference, blood pressure, fasting
      glucose, and lipids. The prevalence of BMI > or = 25 kg/m2 was 25.3% for men and
      28.3% for women. The prevalence of WC >90 cm in men, and >80 cm in women was
      18.5%, and 38.5%, respectively. Clustering of 3 or more CVD risk factors was
      22.7% in men ad 21.7% in women. Using <21 kg/m2; as a referent, subjects with BMI
      of 23 kg/m2; and 27 kg/m2; had an odds ratio of 3.5 and 10.2 in men, and 3.1 and
      6.7 in women, respectively for clustering of CVD risk factors. Using <65 cm as a
      referent, subjects with a WC of > or = 90 cm in men and > or = 85 cm in women had
      an odds ratio of 13.4, and 13.6, respectively for clustering of CVD risk factors.
      Considering the significant associations between clustering of CVD risk factors
      and BMI or WC, the present study suggests that high prevalence of overweight may
      have important implications for the health care system, even at a lower level of
      BMI or WC.

PMID- 14672865
TI  - A new approach to design and implement a lifestyle intervention programme to
      prevent type 2 diabetes in New Zealand Maori.
AB  - Lifestyle programmes provide the greatest opportunity to stem the developing
      epidemic of type 2 diabetes. This is especially relevant to indigenous people
      worldwide, and to Maori in New Zealand. The shift from traditional diets and
      activities to a westernised energy dense diet and a sedentary lifestyle has
      precipitated the rapid increase in Maori developing type 2 diabetes in New
      Zealand. Attendance of Maori to mainstream health clinics or programmes has been
      poor, and a unique approach developed specifically for Maori is required if Maori
      are going to attend and benefit from lifestyle programmes. We describe the
      process involved in developing a successful community programme for Maori and
      outline the novel aspects of the programme which contribute to its acceptability
      and success in the local community.

PMID- 14672866
TI  - Implementation of a successful lifestyle intervention programme for New Zealand
      Maori to reduce the risk of type 2 diabetes and cardiovascular disease.
AB  - Lifestyle programmes have been shown to reduce the risk of type 2 diabetes in
      European populations. The participation of Maori in many mainstream health
      programmes is poor. This study evaluates a lifestyle intervention programme which
      is acceptable to Maori and which has objective outcome measures to determine the
      effectiveness of the programme. Thirty six Maori men and women were recruited for
      a 4 month programme involving modification of diet and exercise. Insulin
      sensitivity was measured using a euglycaemic insulin clamp, body composition
      using dual-energy-absorptiometry and fitness using a submaximal exercise test.
      Secondary outcome measures included anthropometry, blood pressure, fasting
      glucose and insulin levels, and lipid profiles. There was a 24% improvement in
      insulin sensitivity (from 5.1 to 6.3 G/mIU/L, P=0.03, N=29). This was associated
      with a reduction of 3.1 kg in weight (95%CI -4 to -2) and a reduction of 7 mmHg
      in systolic blood pressure (95%CI -13, -1). This approach successfully reduced
      risk for type 2 diabetes and cardiovascular disease in New Zealand Maori in the
      short term.

PMID- 14672867
TI  - Dual forms of malnutrition in the same households in Malaysia--a case study among
      Malay rural households.
AB  - This report is a part of a multi-centre study in Asia on the problem of dual
      forms of malnutrition in the same households. In Malaysia, the prevalence of
      underweight and stunting persist among young children from poor rural areas.
      Overweight in adults, especially women from poor rural areas has been reported in
      recent years. Thus, this study was undertaken in order to assess the presence of
      the dual burden of underweight child-overweight mother pairs in a poor rural
      community. Out of 140 Malay households identified to have at least one child aged
      1-6 years and mother aged above 20 years, 52.1% of the mothers were overweight,
      15.7% of the children were underweight, 27.1% stunted and 5% wasted. Socio
      economic background and food intake frequency data were collected from 54
      underweight child/overweight mother pairs (UW/OW) and 41 normal weight
      child/normal weight mother pairs (NW/NW). Compared with the overweight mothers, a
      higher percentage of the normal weight mothers had received secondary education,
      were employed and with a higher household monthly income, although these
      differences were not significant. Patterns of food intake of the mothers and
      children appeared to have more similarities than differences between the UW/OW
      and NW/NW groups. Quantitative dietary intakes for 2 days using 24-hr recall and
      physical activity energy expenditure over the same period were assessed in a sub
      group of UW/OW and NW/NW mothers and children. The NW/NW children showed
      significantly higher intake of total calories, fat and riboflavin than the UW/OW
      counterparts. Mean energy and nutrient intake of mothers from both groups were
      not significantly different, although the NW/NW mothers showed higher intake
      adequacy for total calories and most nutrients. While most of the mothers from
      both groups reported having no chronic illnesses, about half of the children in
      both groups had infections, especially gastrointestinal infections, over a 2-week
      period. Energy expenditure from physical activity for both UW/OW and NW/NW
      mothers and children did not differ significantly. This study confirmed
      inadequate intake of total energy and nutrients as the major factor for
      underweight in Malay children from rural areas. However, assessing intake and
      physical activity by interview methods were not sensitive enough to overcome
      perceived problems of under-reporting of energy intake and over-estimation of
      energy expenditure, especially by overweight subjects. Further investigations on
      a larger sample are necessary to understand the family dynamics leading to the
      double burden of malnutrition within the same household.

PMID- 14672868
TI  - A case study on dual forms of malnutrition among selected households in District
      1, Tondo, Manila.
AB  - The co-existence of under-and overnutrition in developing countries might be the
      resultant factor of a marked shift in dietary and lifestyle practices of people,
      especially in urban areas. The eating of high fat, high caloric diets, the
      presence of inactive entertainment devices and mechanized labour influence
      patterns of food demand and physical activity. This study identified factors
      associated with the occurrence of under/overweight or normal/normal nutritional
      status of child-mother pairs in one household. This study was conducted in two
      phases. The first phase was a survey of 376 child-mother pairs. The children aged
      33-83 months were attending classes in government day care centres.
      Anthropometric indices: weight-for-age Z score (WAZ) < or = -2SD was used to
      classify underweight in children. WAZ+1 to -1SD was used to indicate normal
      nutritional status in children, specifically for this study, in order to
      establish a more homogenous group. Body mass index (BMI) > or = 25 kg/m2 was used
      to measure overweight among mothers. Results showed that about 59% of the child
      mother pairs were suffering from two different types of malnutrition. From this,
      31 (8.2%) child-mother pairs in the same household were experiencing
      underweight/overweight: the child was underweight and the mother was overweight.
      The second phase of the study was an in-depth study of these 31 under/overweight
      child-mother pairs and 30 randomly selected normal/normal pairs. Pre-tested
      questionnaires were used to gather socio-economic-demographic data; 3 day 24-h
      food recall for dietary intake and 24-h activity recall for physical activity.
      Results showed that the different factors associated with the existence of
      underweight child/overweight mother (UC/OM) or normal child/normal mother (NC/NM)
      in this study were: mother's educational level, mother's occupation, and number
      of children in the household; energy intake, the preference of meats, sweets and
      sugars among children or meats and fried foods among mothers; and mother's
      perception on body size. Physical activity of both mothers and children was
      higher in the UC/OM than in the NC/NM group. The problem of undernutrition and
      overnutrition in one household poses enormous challenges. Although this study
      cannot make an inference to the whole population, the results indicate that there
      is a need to consider whether public health programs should focus on healthy diet
      and lifestyle patterns that will lead to optimal health outcomes at both ends of
      the spectrum of nutritional status.

PMID- 14672869
TI  - Retrospective study of preventive effect of maize on mortality from Parkinson's
      disease in Japan.
AB  - The findings of a negative association between past maize (Zea mays) production
      and current Parkinson's disease mortality by each prefecture in Japan tends to
      support the hypothesis that the nutritional condition that causes niacin
      deficiency might protect people from Parkinson's disease. Specifically, the
      negative association between both the area planted for dried corn in 1960, 1970
      or 1977 and the area planted for sweet corn in 1960 and age-adjusted death rates
      for Parkinson's disease is ecological evidence supporting the hypothesis.
      Extending the analysis to other cultivated crops, even stronger negative
      associations of age-adjusted death rates for Parkinson's disease and cultivation
      of rice and soybeans were found, but associations were not significant for a
      large variety of vegetables. The findings for soybean and rice are attributed to
      the correspondence (co-linearity) of cultivation of these other two seed-crops
      with maize. Hence, further testing of the theory of niacin deprivation and
      prevention of Parkinson's disease finds some circumstantial support in the
      cultivation patterns of a grain of poor niacin and tryptophan availability.

PMID- 14672870
TI  - Haemoglobin status of adult women of two ethnic groups living in a peri-urban
      area of Kolkata city, India: a micro-level study.
AB  - A micro level study on the haemoglobin status of 127 Munda (a tribe) and 174
      Poundrakshatriya (Pod) (caste) women were conducted in the peri-urban area of
      Kolkata City, India. The two ethnic groups were selected in order to find out
      whether populations residing in the same habitat, with similar medical and health
      care facilities have similar haemoglobin status. Results indicate that there
      exists very high percentage of anaemia in both the ethnic groups and 100 percent
      anaemia was observed among the Munda. Mean haemoglobin level was higher among the
      women of both the ethnic groups, consuming calorie, protein, iron and folic acid,
      above the recommended value (Indian Council of Medical Research, 2000). Women
      below the age of 30 years were found to be more anaemic. Education (P <0.001),
      height (P <0.001) and weight (P<0.005) were significantly associated with the
      haemoglobin status of the Pod women. Haemoglobin level of both ethnic groups was
      found to increase with increase in Body Mass Index. Low socioeconomic condition,
      very low literacy rates, poverty and higher live births may have lowered the
      haemoglobin level of the women of the Munda population. However, women of both
      the ethnic groups were found to be anaemic in higher percentage than the state of
      West Bengal and all India (NFHS, 2000). Linear regression analysis indicated that
      expenditure on food had positive effect on the haemoglobin level (P<0.05) of the
      Munda adult women, possibly due to better buying capacity. However, negative
      effect of food expenditure on the haemoglobin level was noticed among the Pod
      women (P<0.05), which may be due to disparity in food sharing within the
      households. Thus populations residing with similar medical and health care
      facilities revealed differences in the haemoglobin level. Differential
      expenditure pattern and food sharing practice seems to be the major factors
      responsible for the differences in haemoglobin status among the adult women in
      this present study. Very low intake of iron and heavy workload may be the reasons
      for this high percentage of anaemia. Moreover, hookworm infections need to be
      analyzed, as its prevalence is very high in India and South Asia. One hundred
      percent anaemia among Munda women is also very alarming. The results suggest that
      government policies should be intensified further at problem specific areas for
      the more vulnerable populations and literacy and antenatal care (especially iron
      supplementation) at various growing periods among the women should be intensified
      to eradicate anaemia.

PMID- 14672871
TI  - Anaemia and vitamin A deficiency in poor urban pregnant women of Bangladesh.
AB  - This cross-sectional study investigated the prevalence of anaemia and vitamin A
      deficiency (VAD) among pregnant women in a poor urban population of Bangladesh.
      It also examined the association of various socio-economic and dietary factors
      with anaemia and vitamin A status. A maternal and child health clinic in Dhaka
      city, Bangladesh was used to obtain the sample. Three hundred and eighty three
      pregnant women, aged 20-30 years, of 20-30 weeks gestation were randomly selected
      from women on their first presentation for antenatal care. Socio-economic,
      pregnancy related information, usual dietary pattern and anthropometric data were
      collected. Blood haemoglobin and serum retinol (vitamin A) concentrations were
      determined. About 40% of the pregnant women were anaemic (haemoglobin <11.0 g/dl)
      and 45% had low serum vitamin A levels (<30 microg/dl); with 8.6% having sub
      clinical VAD (serum retinol <20 microg/dl). The women with low serum vitamin A
      levels had 1.8 times greater risk of being anaemic than did the women with normal
      vitamin A status. Food frequency data revealed that a large proportion of these
      women did not consume egg (49%), milk (25%), meat (31%), liver (83%), large fish
      (32%), small fish (39%) and sweet pumpkin (52%) at all; while about 25% of the
      women reported consuming dark green leafy vegetables (DGLV) and 64% reported an
      intake of fruit at least four servings a week. The pregnant women who were either
      illiterate or received only informal education (up to grade ten) had
      significantly lower haemoglobin and serum vitamin A levels compared to those who
      completed at least a secondary school certificate. The women whose husbands were
      illiterate or received only informal education had significantly (P= 0.01) lower
      serum vitamin A levels than those whose husbands had received at least a
      secondary school certificate. The women who came from families with a per-capita
      income below the poverty line had significantly lower haemoglobin and serum
      vitamin A levels compared to those who came from families with a per-capita
      income above the poverty line. The women who consumed three servings or less of
      DGLV and fruit per week had significantly lower haemoglobin and serum vitamin A
      levels than those who consumed four or more servings a week. The women who never
      consumed large fish had significantly lower haemoglobin compared to those who
      reported at least one serving a week. Furthermore, the women who never consumed
      sweet pumpkin had significantly lower serum vitamin A than the women who ate at
      least one serving a week. By multiple regression analysis, intake of meat, DGLV
      and fruit, and serum vitamin A levels were found to have a significant
      independent relationship with haemoglobin. The overall F-ratio (9.9) was highly
      significant (P=0.000), the adjusted R-square was 0.086 (multiple R=0.309).
      Multiple regression analysis for serum vitamin A also revealed a significant
      independent relationship with per capita income, haemoglobin levels, intakes of
      DGLV and sweet pumpkin. The overall F-ratio (10.2) was highly significant
      (P=0.000), the adjusted R-square was 0.10 (multiple R=0.312). In conclusion,
      anaemia and vitamin A deficiency were highly prevalent among poor urban pregnant
      women in Bangladesh. Various socio-economic and dietary factors may influence the
      anaemia and vitamin A status of these women. The present study emphasizes the
      need for a comprehensive intervention strategy, which include both nutritional
      and environmental factors, to improve the nutritional status of this population.

PMID- 14672872
TI  - Dietary carotenoid intake as a predictor of bone mineral density.
AB  - Our understanding of the influence of nutrition on bone health is limited because
      most studies concentrate on the role of calcium and protein, while other
      nutrients receive less attention. Recent evidence shows a positive link between
      fruit and vegetable consumption and bone health. In the present study, the
      relationships of dietary intakes of preformed retinol and carotenoids, one group
      of phytonutrients abundant in fruit and vegetables, were examined in an Anglo
      Celtic Australian population of 68 men and 137 women. Bone mass of total body and
      lumbar spine were positively related to lycopene intake in men, and to lycopene
      and lutein/zeaxanthin intake in premenopausal women. In addition, a positive
      association of lumbar spine bone mass with dietary beta-carotene intake was
      observed in postmenopausal women. No relationship was found between dietary
      retinol intake and bone mineral status. The finding of the present study suggests
      a beneficial effect of fruit and vegetable consumption, as indicated by dietary
      carotenoid intake, on bone health, possibly via an antioxidant mechanism.

PMID- 14672873
TI  - Inhibitory effects of aqueous crude extract of Saffron (Crocus sativus L.) on
      chemical-induced genotoxicity in mice.
AB  - Saffron (dried stigmas of Crocus sativus L.), was evaluated in the mouse bone
      marrow micronucleus test for its possible protective effects against chromosomal
      damage induced by cisplatin (CIS), mitomycin-C (MMC) and urethane (URE). Three
      doses of saffron (25, 50 and 100 mg/kg body weight) were orally administered to
      mice for five consecutive days prior to administration of genotoxins under
      investigation. From the results obtained, it was evident that the administration
      of 50 and 100 mg saffron/kg body weight could significantly inhibit the in vivo
      genotoxicity of these genotoxins. However, all the three doses of saffron were
      effective in exerting a protective effect against urethane.

PMID- 14672875
TI  - Serum leptin and insulin levels during chronic diurnal fasting.
AB  - Ramadan fasting is a unique model that is associated with restriction of the
      timing of food and fluid intake food from dawn to sunset and reduction in meal
      frequency and sleep duration. Leptin levels are thought to play a role in long
      term regulation of caloric intake and fat deposition. However, the long-term
      changes in leptin levels during this pattern of fasting are not known. The study
      was conducted on lean (N=6, BMI=22.5+/-0.4) and obese (N=18, BMI=33.1+/-1.0)
      healthy female volunteers. Fasting serum levels of leptin, insulin and glucose
      were estimated at baseline (day 1), days 14 and 28 of the month of Ramadan and 2
      weeks after Ramadan. Baseline serum levels of leptin were significantly higher in
      obese (13.5+/-1.96 microg/L,P<0.05) compared with lean subjects (9.60+/-0.80
      microg/L) and correlated positively with body fat (r=0.82, P=0.0004). Serum
      leptin levels exhibited a significant and comparable increase by 39% and 37%
      throughout the month in lean and obese subjects, respectively. In addition, a
      significant correlation (r=0.52, P=0.003) was found between changes in serum
      leptin and serum insulin levels. We conclude that chronic diurnal fasting is
      associated with significant elevations in serum leptin. These elevations appear
      to be mediated by changes in serum levels of insulin. These data support the role
      of insulin in the long-term regulation of leptin secretion during chronic diurnal
      fasting followed by nocturnal eating during the month of Ramadan.

PMID- 14672874
TI  - Whole cereal and legume seeds increase faecal short chain fatty acids compared to
      ground seeds.
AB  - We set out to compare the effect of diets containing intact seeds as food
      ingredients on colon function and fermentation-dependent events. Using a
      randomized cross over design, twelve healthy adults were recruited and required
      to consume an experimental diet containing intact or ground seeds for 7-days then
      after returning to their usual diet for 21-days to consume the second
      experimental diet for 7-days. All foods consumed during the experimental dietary
      periods were supplied by the researchers. Stools passed on three consecutive days
      on the usual diet prior to commencement and on days 5, 6 and 7 during each
      experimental diet, were collected. Outcome measures were whole gut transit time,
      24 h stool output, faecal pH, particle size, and short chain fatty acid content.
      Seeds recovered from stools were examined by scanning electron microscopy. Nine
      of the twelve subjects completed all aspects of the study. Consumption of intact
      seeds compared to ground seeds increased 24 h faecal wet weight (mean 258 g +/-
      123 g and 170 g +/- 63 g, respectively; P=0.005) and dry weight (78 g +/- 34 g
      and 46 g +/- 28 g, respectively; P=0.003). Whole gut transit times and moisture
      content of stools were not different. There was a trend for stools from the whole
      seed diet to be more acidic than those from the ground seed diet (pH 6.2 +/- 0.3
      and pH 6.6 +/- 0.3, respectively; P=0.06) and they contained more short chain
      fatty acids (35 +/- 5.2 and 30 +/- 10.5 mmol/kg, respectively; P=0.05). Large
      amounts of apparently whole seeds were recovered from stools, but internally the
      endosperm was often eroded and coated with bacteria. Intact seeds as food
      ingredients bring about changes to the colonic environment and to faecal
      composition that may reduce the risk of colon cancer.

PMID- 14672876
TI  - Effect of S-allylcysteine on oxidant-antioxidant status during N-methyl-N'-nitro
      N-nitrosoguanidine and saturated sodium chloride-induced gastric carcinogenesis
      in Wistar rats.
AB  - We investigated the chemopreventive effect of S-allylcysteine (SAC), a water
      soluble garlic constituent against gastric carcinogenesis induced in male Wistar
      rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and saturated sodium chloride
      (S-NaCl). The animals were divided into four groups of six animals. Rats in
      groups 1 and 2 were administered MNNG (200 mg/kg body weight) on days 0 and 14 as
      well as S-NaCl (1 mL/rat) three days during weeks 0 to 3, and thereafter placed
      on basal diet until the end of the experiment. Rats in group 2 in addition
      received SAC (200 mg/kg body weight) three times per week starting on the day
      following the first exposure to MNNG and continued until the end of the
      experimental period. Group 3 animals were given SAC alone as in group 2. Group 4
      animals received basal diet and tap water throughout the experiment and served as
      the untreated control. The animals were sacrificed after an experimental period
      of 21 weeks. Measurement of lipid peroxidation and antioxidants of the
      glutathione redox cycle in the stomach tissue, liver and venous blood was used to
      monitor the chemopreventive potential of SAC. All animals that received MNNG and
      S-NaCl alone, developed tumours, identified histologically as squamous cell
      carcinomas. In the tumour tissue, diminished lipid peroxidation was accompanied
      by increase in reduced glutathione (GSH) and GSH-dependent enzymes, whereas in
      the liver and circulation, enhanced lipid peroxidation was associated with
      antioxidant depletion. Administration of SAC suppressed the incidence of MNNG+S
      NaCl-induced gastric tumours as revealed by the absence of carcinomas. SAC
      ameliorated MNNG-induced decreased susceptibility of the gastric mucosa to lipid
      peroxidation, whilst simultaneously increasing the antioxidant status. In the
      liver and blood, SAC reduced the extent of lipid peroxidation and significantly
      enhanced antioxidant activities. We suggest that SAC exerts its chemopreventive
      effects by modulating lipid peroxidation and enhancing GSH-dependent antioxidants
      in the target organ as well as in the liver and blood.

PMID- 14672877
TI  - Using endothelial progenitor cells for gene therapy.

PMID- 14672878
TI  - JAM-1 regulation of endothelial cell migration: implications for angiogenesis.

PMID- 14672879
TI  - Out of balance: a role of impaired superoxide dismutase activity for vascular
      constrictive remodeling after angioplasty.

PMID- 14672880
TI  - Inflammation-sensitive plasma proteins and incidence of myocardial infarction in
      men with low cardiovascular risk.
AB  - OBJECTIVE: Myocardial infarction (MI) is sometimes experienced by individuals
      without any traditional risk factor. This prospective study explored whether
      incidence of MI in nonsmoking, nondiabetic men with normal blood pressure and
      serum lipids is related to inflammation-sensitive plasma proteins (ISPs). METHODS
      AND RESULTS: Five ISPs (alpha1-antitrypsin, haptoglobin, ceruloplasmin,
      fibrinogen, orosomucoid) were analyzed in 6075 men, 47+/-3.6 years old. A low
      risk group (no traditional risk factor, n=1108) and a high-risk group (> or =2
      major risk factors, n=1011) were defined. Incidence of MI (n=227) was monitored
      over 18.1+/-4.3 years of follow-up. In the low-risk group, the age-adjusted
      relative risks (RRs) were 1.00 (reference), 1.9 (95% CI, 0.8 to 4.2), 1.8 (95%
      CI, 0.6 to 5.4), and 2.9 (95% CI, 1.05 to 8.1), respectively, for men with 0, 1,
      2 and > or =3 ISPs in the top quartile (trend: P=0.03). In this group, the
      increased risk was observed only after > or =10 years of follow-up. In the high
      risk group, the age-adjusted RRs were 1.00, 1.4 (95% CI, 0.9 to 2.2), 1.9 (95%
      CI, 1.2 to 3.1), and 2.0 (95% CI, 1.3 to 3.1), respectively, for men with 0, 1,
      2, and > or =3 ISPs in the top quartile (trend: P=0.0004). CONCLUSIONS: Incidence
      of MI in nonsmoking, nondiabetic men with normal blood pressure and lipids was
      related to ISPs. The causes for this relationship remain to be explored.

PMID- 14672881
TI  - TSH stimulates IL-6 secretion from adipocytes in culture.

PMID- 14672882
TI  - Degenerative musculoskeletal disease.

PMID- 14672883
TI  - TNF inhibitors in the treatment of rheumatoid arthritis in clinical practice:
      costs and outcomes in a follow up study of patients with RA treated with
      etanercept or infliximab in southern Sweden.
AB  - OBJECTIVES: To evaluate costs, benefits, and cost effectiveness of tumour
      necrosis factor inhibitor treatment over one year in routine clinical practice.
      MATERIALS AND METHODS: At four rheumatology units in southern Sweden treatment of
      160 consecutive patients with RA was started with either etanercept or
      infliximab. The economic analysis was based on 116 patients with complete data
      who received treatment for at least one year. Details on drug treatment,
      functional capacity, disease activity, and laboratory values were available
      during the entire treatment. Information on resource use and QoL was collected at
      baseline and throughout the first year. The cost effectiveness analysis was based
      on changes in outcome and costs compared with the year before treatment. Cost per
      quality adjusted life year (QALY) gained was calculated for the entire sample and
      for patients with different levels of functional disability. RESULTS: During the
      first treatment year direct costs were reduced by 40%, but indirect costs did not
      change substantially. Patients' QoL improved on treatment-utility increased from
      an average of 0.28 to 0.65. Assuming that improvement occurred after three
      months' treatment, the cost per QALY gained is estimated as euro;43 500. If it
      occurs after six weeks, in parallel with clinical measures, the cost per QALY is
      euro;36 900. Sensitivity analysis, including all 160 patients, gave an estimated
      cost per QALY of euro;53 600. The cost per QALY increases for patient groups with
      less severe disease. CONCLUSION: For this patient group, cost effectiveness
      ratios are within the generally accepted threshold of euro;50 000, but need to be
      confirmed with larger samples.

PMID- 14672884
TI  - Differential diagnosis of calf pain with musculoskeletal ultrasound imaging.

PMID- 14672885
TI  - Case number 28: rheumatoid arthritis and congenitally short fourth metacarpals.

PMID- 14672886
TI  - Bone loss in unclassified polyarthritis and early rheumatoid arthritis is better
      detected by digital x ray radiogrammetry than dual x ray absorptiometry:
      relationship with disease activity and radiographic outcome.
AB  - OBJECTIVE: To compare changes in regional bone mineral density (BMD) of the
      metacarpal joints measured by dual x ray absorptiometry (DXA) and digital x ray
      radiogrammetry (DXR) in relation to disease activity and radiographic outcome in
      a two year follow up study of patients with early RA and unclassified
      polyarthritis. PATIENTS AND METHODS: 72 patients with symmetrically swollen and
      tender second and third metacarpophalangeal or proximal interphalangeal joints
      for at least four weeks and less than two years were included. 51 patients
      fulfilled the ACR criteria for RA. 21 patients had unclassified polyarthritis.
      The patients with RA were divided into groups according to mean disease activity,
      average glucocorticoid dose, and MRI and x ray detected bone erosions in the
      hands. Clinical and biochemical measurements were made every month and an x ray
      examination of the hands and BMD of the metacarpal joints every six months.
      RESULTS: DXR BMD decreased significantly only in patients with RA from month 6
      and was associated with the mean disease activity. Patients with RA and erosive
      as well as non-erosive disease showed a significant decrease in the rate of bone
      loss, greatest in those with erosive disease. No changes in BMD measured by DXA
      were seen in any patient group. CONCLUSION: DXR is a useful measure of the
      destructive disease activity in patients with RA and unclassified polyarthritis,
      providing valuable information about bone changes associated with disease
      activity and erosive disease in early RA. DXR is better than DXA for detecting
      and monitoring periarticular osteoporosis of the metacarpal bone.

PMID- 14672887
TI  - A randomised controlled trial of occupational therapy for people with early
      rheumatoid arthritis.
AB  - BACKGROUND: Occupational therapy (OT) aims at improving performance of daily
      living tasks, facilitating successful adjustments in lifestyle, and preventing
      losses of function. OBJECTIVE: To evaluate the effects of a pragmatic,
      comprehensive OT programme on self management and health status of people with
      early rheumatoid arthritis (RA) (<2.5 years). METHODS: A randomised, controlled
      "assessor blinded" trial was conducted with assessments made at entry, 6, 12, and
      24 months. Main outcomes were AIMS2: physical function (PF), pain visual analogue
      scale (VAS), and Arthritis Self-Efficacy Scale (ASES). RESULTS: Groups had
      similar disease duration (9 months OT (n = 162) v 10 months control (n = 164)).
      The OT group received 7.57 (SD 3.04) hours of therapy. Self management
      significantly increased in the OT group. Otherwise, there were no significant
      differences in any outcome measures, or between groups, by ACR functional class:
      AIMS2: PF (F = 0.04; p = 0.96); pain VAS (F = 0.29; p = 0.74); total ASES score
      (F = 0.93; p = 0.39). CONCLUSIONS: OT improved self management but not health
      status in early RA. Functional ability remains reasonably good for many in the
      first five years, so preventive benefits of self management may not yet be
      apparent and longer follow up is needed. Although many considered the education
      and therapy useful, insufficient numbers in the OT group used self management
      sufficiently to make a difference. Behavioural approaches can improve adherence
      and, potentially, the long term benefits. Future research should evaluate OT as a
      complex intervention and develop programmes from a theoretical and evidence base.

PMID- 14672889
TI  - Satisfactory cross cultural equivalence of the Dutch WOMAC in patients with hip
      osteoarthritis waiting for arthroplasty.
AB  - BACKGROUND: Cross cultural validity is of vital importance for international
      comparisons. OBJECTIVE: To investigate the validity of international Dutch
      English comparisons when using the Dutch translation of the Western Ontario and
      McMaster Universities osteoarthritis index (WOMAC). PATIENTS AND METHODS: The
      dimensionality, reliability, construct validity, and cross cultural equivalence
      of the Dutch WOMAC in Dutch and Canadian patients waiting for primary total hip
      arthroplasty was investigated. Unidimensionality and cross cultural equivalence
      was quantified by principal component and Rasch analysis. Intratest reliability
      was quantified with Cronbach's alpha, and test-retest reliability with the
      intraclass correlation coefficient. Construct validity was quantified by
      correlating sum scores of the Dutch WOMAC, Arthritis Impact Measurement Scales
      (Dutch AIMS2), Health Assessment Questionnaire (Dutch HAQ), and Harris Hip Score
      (Dutch HHS). RESULTS: The WOMAC was completed by 180 Dutch and 244 English
      speaking Canadian patients. Unidimensionality of the Dutch WOMAC was confirmed by
      principal component and Rasch analysis (good fit for 20/22 items). The intratest
      reliability of the Dutch WOMAC for pain and physical functioning was 0.88 and
      0.96, whereas the test-retest reliability was 0.77 and 0.92, respectively. Dutch
      WOMAC pain sum score correlated 0.69 with Dutch HAQ pain, and 0.39 with Dutch HHS
      pain. Dutch WOMAC physical functioning sum score correlated 0.46 with Dutch AIMS2
      mobility, 0.62 with Dutch AIMS2 walking and bending, 0.67 with Dutch HAQ
      disability, and 0.49 with Dutch HHS function. Differential item functioning (DIF)
      was shown for 6/22 Dutch items. CONCLUSIONS: The Dutch WOMAC permits valid
      international Dutch-English comparisons after correction for DIF.

PMID- 14672888
TI  - Endothelial dysfunction in young patients with rheumatoid arthritis and low
      disease activity.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased risk of
      cardiovascular disease. Endothelial dysfunction represents the earliest stage of
      atherosclerosis. OBJECTIVE: To evaluate the influence of chronic inflammatory
      state on endothelial function in patients with RA by measuring endothelial
      reactivity in young patients with RA with low disease activity and without
      traditional cardiovascular risk factors. METHODS: Brachial flow mediated
      vasodilatation (FMV), assessed by non-invasive ultrasound, was evaluated in 32
      young to middle aged patients with RA (age </=59 years), with DAS28 </=3.2 and
      without overt cardiovascular disease, and in 28 age and sex matched controls.
      RESULTS: Mean (SD) FMV was significantly lower in patients than in controls (3.2
      (1.3)% v 5.7 (2.0)%; p<0.001), inversely related to low density lipoprotein
      cholesterol (r = -0.45, p<0.05) and C reactive protein (CRP), expressed as the
      value at the moment of ultrasound evaluation (r = -0.44, p<0.05), as the average
      of CRP levels evaluated at different times during the disease (r = -0.47,
      p<0.05), or as the average of >/=4 determinations multiplied by the disease
      duration (r = -0.40, p<0.05). In a multivariate regression model, a lower
      brachial flow mediated vasodilatation was independently predicted by low density
      lipoprotein cholesterol (beta = -0.40, p<0.05), average CRP levels multiplied by
      the disease duration (beta = -0.44, p<0.05), and brachial artery diameter (beta =
      -0.28, p<0.05). CONCLUSIONS: Young to middle aged patients with RA with low
      disease activity, free from cardiovascular risk factors and overt cardiovascular
      disease, have an altered endothelial reactivity that seems to be primarily
      related to the disease associated chronic inflammatory condition.

PMID- 14672890
TI  - Interferon beta stimulates interleukin 1 receptor antagonist production in human
      articular chondrocytes and synovial fibroblasts.
AB  - BACKGROUND: Interferon (IFN) beta displays anti-inflammatory and
      immunosuppressive activity and has been considered for the treatment of
      rheumatoid arthritis (RA). Information about the effects of this molecule on
      joint cells is scarce, however. OBJECTIVE: To investigate the effects of IFNbeta
      on the production of interleukin-1 receptor antagonist (IL1Ra) in human articular
      chondrocytes and synovial fibroblasts. METHODS: Chondrocytes and synovial
      fibroblasts were stimulated with IFNbeta alone or in combination with interleukin
      (IL) 1beta. IL1Ra concentrations in culture supernatants and cell lysates were
      determined by ELISA. Expression of mRNA encoding the secreted sIL1Ra or the
      intracellular icIL1Ra1 isoforms was quantified by real time reverse transcriptase
      polymerase chain reaction. RESULTS: In chondrocytes, IFNbeta alone had no effect,
      but dose dependently enhanced the secretion of IL1Ra induced by IL1beta.
      Chondrocyte cell lysates contained undetectable or low levels of IL1Ra, even
      after stimulation with IL1beta and IFNbeta. Consistently, IL1beta and IFNbeta
      induced sIL1Ra mRNA expression in chondrocytes, while expression of icIL1Ra1 was
      not detectable. Human articular chondrocytes thus mainly produce secreted IL1Ra.
      In synovial fibroblasts, IFNbeta alone dose dependently increased IL1Ra
      secretion. In addition, IFNbeta enhanced the stimulatory effect of IL1beta on
      IL1Ra production. In synovial cell lysates, IFNbeta and IL1beta also increased
      IL1Ra levels. Consistently, IFNbeta and IL1beta induced the expression of both
      sIL1Ra and icIL1Ra1 mRNA in synovial fibroblasts. CONCLUSION: IFNbeta increases
      IL1Ra production in joint cells, which may be beneficial in cartilage damaging
      diseases such as RA or osteoarthritis.

PMID- 14672891
TI  - Long term prognosis of children born to lupus patients.
AB  - OBJECTIVE: To determine the long term prognosis of children of patients with
      systemic lupus erythematosus (SLE). METHODS: Children of patients with SLE were
      invited to attend our clinic for physical examination and laboratory tests. A
      total of 195 children (aged 4 months to 26 years; male = 82, female = 113) were
      examined in 1991, 1995, 1997, and 1998. RESULTS: Two cases were diagnosed as SLE
      at the first visit and were excluded from the second visit. A significantly
      higher percentage (52/195 (27%)) of patients were positive for antinuclear
      antibodies (ANA) at a cut off serum dilution of 1/40 compared with controls (4/57
      (7%)). ANA were detected more frequently in female subjects than in men (p<0.05).
      Forty four subjects were examined on more than two occasions. Nine of the 10
      patients who were positive for ANA at the second visit were girls aged 4-8 years.
      The incidence of anti-DNA and antiphospholipid antibodies in children of patients
      with SLE was similar to that in the controls. CONCLUSIONS: The finding that
      children, especially girls, born to maternal lupus patients had a high positive
      rate for ANA suggests that a genetic factor is involved in SLE pathogenesis.
      Longitudinal observation of these patients may provide important clinical
      information and clues to the pathogenesis of SLE.

PMID- 14672892
TI  - Selective T cell receptor decrease in peripheral blood T lymphocytes of patients
      with polymyalgia rheumatica and giant cell arteritis.
AB  - OBJECTIVES: To investigate the phenotype and T cell receptor (TCR) use in
      peripheral blood T cells in patients with polymyalgia rheumatica (PMR) and giant
      cell arteritis (GCA). METHODS: Circulating T lymphocyte phenotype and TCR
      repertoire were studied by flow cytometry using specific monoclonal antibodies in
      23 healthy controls and 37 patients with PMR/GCA. RESULTS: Patients with active
      PMR/GCA showed an inverse relation between naive and memory CD4+ T cells and
      unchanged expression of activation surface markers compared with controls. CD4+
      TCR BV expansions were seen in 12 (52%) controls and in 8 (22%) patients with
      active disease (p = 0.03). Within the CD8+ subset, the frequency of expansions
      was similar between groups. Most T cell expansions remained stable over time.
      Seventeen of the 23 patients with active PMR/GCA disclosed a simultaneous CD4+
      and CD8+ T cell depletion for at least one particular BV family with a clear
      predominance of BV5S2/S3. CONCLUSIONS: The phenotype of circulating T cells in
      patients with PMR/GCA is similar to that found in aged healthy subjects, except
      for the surface markers of naive and memory cells and a striking non-activated
      phenotype. Specific BV expansions in CD4+ and CD8+ T cells, which remain stable
      over time, are frequent in aged subjects, including patients with PMR/GCA. TCR BV
      changes in patients with active disease seem to be also age related, except for
      the significant decrease in certain BV families in both CD4+ and CD8+ T cell
      subsets, which may favour the participation of a superantigen stimulation in
      PMR/GCA.

PMID- 14672893
TI  - Physiological levels of hydrocortisone maintain an optimal chondrocyte
      extracellular matrix metabolism.
AB  - OBJECTIVE: To investigate the effects of physiological doses of hydrocortisone on
      synthesis and turnover of cell associated matrix (CAM) by human chondrocytes
      obtained from normal articular cartilage. METHODS: Human articular cartilage
      cells were obtained from visually intact cartilage of the femoral condyles of
      five donors and maintained in culture for one week to reach equilibrium in
      accumulated CAM compounds. 0, 0.05, 0.20, and 1.0 micro g/ml hydrocortisone was
      added to the nutrient media during the entire culture period. Cells were
      liberated and levels of CAM aggrecan, type II collagen, and fibronectin, of
      intracellular IGF-1, IL1alpha and beta, and of their respective plasma membrane
      bound receptors IGFR1, IL1RI, and the decoy receptor IL1RII, were assayed by flow
      cytometry. RESULTS: In comparison with controls, hydrocortisone treated
      chondrocytes, at all concentrations, expressed significantly higher plasma
      membrane bound IGFR1. Intracellular IGF-1 levels remained unchanged. Together
      with these changes, reflecting an increased ability to synthesise extracellular
      matrix (ECM) macromolecules, hydrocortisone treated cells expressed significantly
      higher amounts of the plasma membrane bound decoy IL1RII. Concurrently,
      intracellular IL1alpha and beta levels and membrane bound IL1RI were down
      regulated. Levels of CAM aggrecan, type II collagen, and fibronectin were
      significantly up regulated in the chondrocytes treated with hydrocortisone.
      CONCLUSION: 0.05 micro g/ml hydrocortisone treated chondrocytes had decreased
      catabolic signalling pathways and showed an enhanced ability to synthesise ECM
      macromolecules. Because IL1 activity was decreased and the expression of IL1RII
      decoy receptor enhanced, more of the ECM macromolecules produced remained
      accumulated in the CAM of the chondrocytes. The effects were obtained at doses
      comparable with physiological plasma levels of hydrocortisone in humans.

PMID- 14672894
TI  - Metabolic activation stimulates acid secretion and expression of matrix degrading
      proteases in human osteoblasts.
AB  - BACKGROUND: Both cellular and matrix components of healthy bone are permanently
      renewed in a balanced homoeostasis. Osteoclastic bone resorption involves the
      expression of vacuolar-type ATPase proton pumps (vATPase) on the outer cell
      membrane and the secretion of matrix degrading proteases. Osteoblasts modulate
      the deposition of bone mineral components and secrete extracellular matrix
      proteins. OBJECTIVES: To investigate the ability of osteoblasts and osteosarcoma
      to secrete acid and express matrix degrading proteases upon metabolic activation.
      To examine also the potential contribution of vATPases to proton secretion
      expressed on osteoblasts. METHODS: Osteoblasts were isolated from trabecular bone
      and characterised by reverse transcriptase-polymerase chain reaction and
      immunohistochemistry. Proton secretion was analysed by a cytosensor
      microphysiometer. RESULTS: Osteoblasts not only express matrix degrading
      proteases upon stimulation with tumour necrosis factor or with phorbol ester but
      they also secrete protons upon activation. Proton secretion by osteoblasts is
      associated partially with proton pump ATPases. CONCLUSION: These data suggest
      that, in addition to monocyte derived osteoclasts, cytokine activated mesenchymal
      osteoblasts and osteosarcoma cells may contribute to the acidic milieu required
      for bone degradation.

PMID- 14672895
TI  - Collagen type I alpha1 Sp1 polymorphism, osteoporosis, and intervertebral disc
      degeneration in older men and women.
AB  - OBJECTIVES: To examine whether collagen type I alpha1 (COLIA1) Sp1 polymorphism
      is associated with osteoporosis and/or intervertebral disc degeneration in older
      people. METHODS: COLIA1 genotype was determined in 966 men and women (>/=65
      years) of the Longitudinal Aging Study Amsterdam. The guanine (G) to thymidine
      (T) polymorphism in the first intron of the COLIA1 gene was detected by PCR and
      MscI digestion. In the total sample, quantitative ultrasound (QUS) measurements,
      serum osteocalcin (OC), and urine deoxypyridinoline (DPD/Cr(urine)) were
      assessed. A follow up of fractures was done every three months. In a subsample,
      total body bone mineral content (n = 485) and bone mineral density (BMD) of the
      hip and lumbar spine (n = 512) were measured by dual energy x ray absorptiometry
      (DXA). Prevalent vertebral deformities and intervertebral disc degeneration were
      identified on radiographs (n = 517). RESULTS: People with the TT genotype had a
      higher risk of disc degeneration than those with the GG and GT genotypes (OR =
      3.6; 95% CI 1.3 to 10). For men, higher levels of OC were found in those with the
      T allele than in those without it (GG v (GT+TT) 1.96 (0.06) nmol/l v 2.19 (0.09)
      nmol/l). COLIA1 polymorphism was not significantly associated with other measures
      of osteoporosis in either men or women. CONCLUSION: COLIA1 Sp1 polymorphism may
      be a genetic risk factor related to intervertebral disc degeneration in older
      people. Previously reported associations between the COLIAI Sp1 genotype and
      lower BMD or QUS values, higher levels of DPD/Cr, and an increased fracture risk
      in either men or women could not be confirmed.

PMID- 14672897
TI  - Cytokine correlates of clinical response patterns to infliximab treatment of
      ankylosing spondylitis.
AB  - OBJECTIVE: To identify clinical and immunological markers of response to
      treatment with infliximab in ankylosing spondylitis (AS). METHODS: Baseline and
      sequential cytokine levels (IL1, TNFalpha, IFNgamma, TGFbeta and IL10) were
      examined after 52 weeks of infliximab treatment 5 mg/kg in 22 patients. RESULTS:
      At week 52, 18 patients were responders and four non-responders according to ASAS
      group criteria. Clinical measures of disease activity between the two groups at
      baseline were similar, apart from a trend towards longer disease duration in non
      responders (p = 0.08). Baseline CRP and TNFalpha levels were higher in responders
      than non-responders (p<0.01 and p<0.006, respectively). The two groups had
      similar baseline cytokine levels, apart from TNFalpha. Baseline CRP levels did
      not correlate significantly with baseline cytokine levels in responders, but a
      strong correlation was noted between baseline CRP and IL1, IFNgamma, and IL10 in
      non-responders. Apart from an early rise in TGFbeta and a decrease in IL10 in
      responders after the first infusion, sequential cytokine analysis for the first
      six months of treatment was not related to clinical disease activity measures.
      CONCLUSION: Although sequential cytokine analysis does not appear to be
      informative, baseline CRP and TNFalpha levels are useful markers of clinical
      response patterns in patients with AS treated with infliximab.

PMID- 14672896
TI  - Treatment with licofelone prevents abnormal subchondral bone cell metabolism in
      experimental dog osteoarthritis.
AB  - OBJECTIVES: To determine if treatment with licofelone, a combined 5-lipoxygenase
      and cyclo-oxygenase inhibitor, in vivo in experimental dog osteoarthritis can
      modify bone cell metabolism in long term in vitro subchondral osteoblast cell
      cultures (Ob). METHODS: Group 1 received sectioning of the anterior cruciate
      ligament (ACL) of the right knee with no active treatment (placebo group). Groups
      2 and 3 received sectioning of the ACL of the right knee, and were given
      licofelone (2.5 or 5.0 mg/kg daily by mouth, respectively) for eight weeks
      beginning the day after surgery. Primary Ob were prepared from the subchondral
      bone plate. Levels of phenotypic markers (alkaline phosphatase activity,
      osteocalcin release), and urokinase plasminogen activator (uPA) and insulin-like
      growth factor-1 (IGF-I) levels, were evaluated in each group. Lastly,
      prostaglandin E(2) (PGE(2)) and leucotriene B(4) levels were evaluated. RESULTS:
      No significant differences in alkaline phosphatase activity or osteocalcin
      release from Ob between the three groups, under either basal or 1,25(OH)(2)D(3)
      induction were seen. In contrast, treatment with licofelone reduced uPA and IGF-I
      levels in Ob. PGE(2) levels, which were still raised in the placebo group, were
      decreased sharply by licofelone. A relationship was found between licofelone
      treatment and either the reduction in the size of lesions on tibial plateaus or
      the levels of uPA, IGF-I, or PGE(2). CONCLUSIONS: Licofelone treatment prevents
      and/or delays the abnormal metabolism of subchondral osteoblasts in this model.
      Licofelone reduced PGE(2) levels after long term Ob, suggesting that the
      reduction in uPA and IGF-I levels is linked, at least in part, to this reduction.

PMID- 14672898
TI  - Effect of the first infliximab infusion on sleep and alertness in patients with
      active rheumatoid arthritis.
AB  - OBJECTIVE: To assess the benefit of the first infliximab infusion on sleep
      disturbances in patients with RA Material and methods: Evaluation of RA activity,
      sleepiness (Epworth scale and multiple sleep latency test), alertness (steer
      clear test), and sleep structure (polysomnography) were conducted before and
      after the first infusion of infliximab in six female patients with RA. RESULTS:
      The day after the first infliximab infusion, the mean (SD) number of tender (20
      (2.4)) or swollen (15.3 (2)) joints and the morning stiffness (140 (61.9) min)
      had not changed. There were significant improvements in the median number of
      total sleep stage transitions per hour (median (IR) before v after infusion: 20.5
      (43) v 7.5 (6); Wilcoxon paired test, p = 0.014), median percentage of phase I+II
      (83.5 (8) v 54.5 (24); p = 0.023), percentage of REM stages (2 (10) v 11.5 (8); p
      = 0.014), median percentage sleep efficiency (44 (22) v 75 (18); p = 0.014),
      median sleep latency (77.5 (150) v 25.5 (23) min; p = 0.023), and median number
      of hits in the steer clear test (48.5 (86) v 6 (45); p = 0.023). Neither
      objective nor subjective daytime sleepiness was noted. One obese patient had
      obstructive sleep apnoea syndrome. CONCLUSIONS: Sleep and the alertness
      disturbances in RA improve with infliximab treatment. Improvement appears
      unrelated to joint discomfort amelioration but suggests a central effect through
      inhibition of circulating TNFalpha levels.

PMID- 14672899
TI  - Systemic lupus erythematosus and genetic variation in the interleukin 1 gene
      cluster: a population based study in the southeastern United States.
AB  - BACKGROUND: Interleukin (IL)1alpha and IL1beta, and their endogenous receptor
      antagonist (IL1Ra), have been related to the pathology of systemic lupus
      erythematosus (SLE), but the role of IL1 polymorphisms in the aetiology of SLE is
      unknown. OBJECTIVE: To examine polymorphisms at IL1alpha -889(C-->T), IL1alpha
      +4845(C-->T), IL1beta -511(C-->T), IL1beta +3953(G-->T), and IL1Ra (86 bp VNTR)
      in a population based study of SLE in North Carolina and South Carolina. METHODS:
      Genotypes from 230 cases who met ACR classification criteria, and from 275
      controls matched for age, sex, and state, were analysed separately for African
      Americans and whites. Odds ratios (ORs) were estimated by logistic regression
      models for each locus alone and also after adjusting for polymorphisms at
      adjacent loci. RESULTS: An increased risk of SLE for the IL1alpha -889C/C
      genotype compared with carriage of the -889T allele was found in both African
      Americans (OR = 3.1, p = 0.001) and whites (OR = 2.9, p = 0.005). In African
      Americans, carriage of the IL1beta -511T allele was associated with a higher risk
      of SLE than carriage of the -511C/C genotype (OR = 2.4, p = 0.017), independent
      of variation at IL1alpha -889. CONCLUSIONS: The observed associations support the
      hypothesis that genetic variation in IL1 is involved in the aetiology of SLE and
      merit further investigation.

PMID- 14672900
TI  - Anti-apoptogenic function of TGFbeta1 for human synovial cells: TGFbeta1 protects
      cultured synovial cells from mitochondrial perturbation induced by several
      apoptogenic stimuli.
AB  - OBJECTIVE: To investigate anti-apoptogenic mechanism of transforming growth
      factor beta1 (TGFbeta1) towards synovial cells. METHODS: Isolated synovial cells,
      treated or not with TGFbeta1, were cultured in the presence or absence of anti
      Fas IgM, proteasome inhibitor Z-Leu-Leu-Leu-aldehyde (LLL-CHO), etoposide, or C2
      ceramide. After cultivation, apoptosis of synovial cells was examined by the
      presence of hypodiploid DNA(+) cells, the presence of terminal deoxy (d)-UTP nick
      end labelling(+) cells (TUNEL(+) cells), activation of caspases, and disruption
      of mitochondrial transmembrane potential (DeltaPsim). RESULTS: Activation of
      caspase-9 and DeltaPsim was found in anti-Fas IgM treated synovial cells. The
      increment of both hypodiploid DNA(+) cells and TUNEL(+) cells accompanied by the
      activation of caspase-8 and caspase-3 was also determined in anti-Fas IgM treated
      synovial cells. These hallmarks for apoptosis induced by anti-Fas IgM were
      significantly suppressed in TGFbeta1 treated synovial cells. LLL-CHO, etoposide,
      and C2-ceramide also caused DeltaPsim, the increment of both hypodiploid DNA(+)
      cells and TUNEL(+) cells, and the activation of both Leu-Glu-His-Asp ase
      (LEHDase; caspase-9 like activity) and Asp-Glu-Val-Asp ase (DEVDase; caspase-3
      like activity) in synovial cells. As determined in anti-Fas IgM treatment,
      TGFbeta1 significantly reduced apoptotic cell death of synovial cells induced by
      the above chemicals. CONCLUSIONS: The protective effect of TGFbeta1 for
      mitochondrial homoeostasis may be important in the anti-apoptogenic function of
      TGFbeta1 for synovial cells.

PMID- 14672901
TI  - Fas gene promoter polymorphisms in primary Sjogren's syndrome.
AB  - BACKGROUND: Fas mediated apoptosis may be important in the pathogenesis of
      primary Sjogren's syndrome (pSS). OBJECTIVE: To examine genetic variation in the
      promoter region of the Fas gene in pSS. METHODS: Two single nucleotide
      polymorphisms at positions -1377(G/A) and -670(G/A) in the Fas gene promoter were
      genotyped by PCR-SSP in 101 patients with pSS and 108 Caucasoid controls.
      RESULTS: No significant differences in allele or genotype frequencies were
      detected between the patients with pSS and controls. However, significant
      associations were observed with Ro/La autoantibody negative patients, who display
      milder and later onset disease. The -670A allele was more frequent in Ro/La
      autoantibody negative patients than in Ro/La autoantibody positive patients (p =
      0.04). CONCLUSION: This study does not confirm an earlier report of an
      association between pSS and the Fas promoter -670G allele. However, the results
      suggest that genetically determined variability in Fas expression may modulate
      Ro/La autoantibody responses in patients with pSS.

PMID- 14672902
TI  - Treatment of resistant rheumatoid arthritis by intra-articular infliximab
      injections: a pilot study.

PMID- 14672903
TI  - Coeliac disease associated with systemic sclerosis.

PMID- 14672904
TI  - Septic arthritis caused by Moraxella catarrhalis associated with infliximab
      treatment in a patient with undifferentiated spondarthritis.

PMID- 14672905
TI  - Lack of association between angiotensin converting enzyme gene polymorphism and
      Korean Behcet's disease.

PMID- 14672906
TI  - Spontaneous pregnancy in a woman with lupus and thyroiditis despite imminent
      premature ovarian failure.

PMID- 14672907
TI  - Doppler ultrasound identifies increased resistive indices in SSc.

PMID- 14672908
TI  - Differences in the management of shoulder pain between primary and secondary care
      in Europe: time for a consensus.

PMID- 14672909
TI  - Exercise in juvenile idiopathic arthritis: promise or passe.

PMID- 14672910
TI  - Progressive multifocal leucoencephalopathy and immunosuppression.

PMID- 14672911
TI  - Relationships between seed germinability of Spergularia marina (Caryophyllaceae)
      and the formation of zonal communities in an inland salt marsh.
AB  - BACKGROUND AND AIMS: The formation of zonal communities may be attributed to
      differences in germination across the community and to timing of germination of
      seeds present in the seed bank. Our goals were two-fold: (1) to assess the annual
      germination pattern of Spergularia marina; and (2) to determine whether
      germination of S. marina differed across zonal communities. METHODS: Fresh seeds
      were buried in an experimental garden in polyester bags. Bags were harvested
      monthly for 1 year and exposed to differing 12 h/12 h temperature regimes (5/15
      degrees C, 5/25 degrees C, 15/25 degrees C and 20/35 degrees C) with a 12 h
      dark/12 h light photoperiod. Replicate seeds were exposed to 24 h dark. Seeds
      were also placed in different zonal communities to assess germinability in the
      field. KEY RESULTS: Spergularia marina has a primary physiological dormancy.
      Conditional dormancy occurs from December to May and non-dormancy from June to
      November. Field germination initiates in the spring when temperatures are cool
      and salinity is low due to flooding, and ceases in the summer when temperatures
      exceed germination requirements. Spergularia marina has a light requirement for
      germination. CONCLUSIONS: If seeds become buried in the field or are light
      inhibited by Phragmites australis, they will remain dormant until they receive an
      adequate amount of light for germination. Since S. marina can germinate across
      all zones in a salt-marsh community, the formation of zonal communities is not
      determined at the germination stage, but at some later stage of development.

PMID- 14672912
TI  - Chemical and physical defence in early and late leaves in three heterophyllous
      birch species native to northern Japan.
AB  - BACKGROUND AND AIMS: Betula ermanii, B. maximowicziana and B. platyphylla var.
      japonica have heterophyllous leaves (i.e. early leaves and late leaves) and are
      typical pioneer species in northern Japan. Chemical and physical defences against
      herbivores in early and late leaves of these species were studied. METHODS: Two
      year-old seedlings were grown under full sunlight in a single growing season.
      Three-week-old leaves of each seedling were harvested three times (May, July and
      October). Total phenolics and condensed tannin content were determined for
      chemical defence and leaf toughness and trichome density were assessed for
      physical defence. Defoliation of early leaves in May was also performed to study
      the contribution of early leaves to subsequent growth. KEY RESULTS: Chemical and
      physical defences were greater in early than late leaves in B. platyphylla and B.
      ermanii, whereas the reverse was true in B. maximowicziana. In contrast to its
      weak chemical defences, the trichome density in B. maximowicziana was very high.
      In B. platyphylla and B. ermanii, the relative growth rates (RGR) were greater
      early in the growing season. Negative effects on growth of removal of early
      leaves were significant only in B. platyphylla. CONCLUSIONS: B. platyphylla and
      B. ermanii invest in defence in early rather than late leaves, since early leaves
      are crucial to subsequent growth. In contrast, B. maximowicziana more strongly
      defends its late leaves, since its RGR is maintained at the same level throughout
      the growing season.

PMID- 14672913
TI  - Epithelial-mesenchymal interactions are linked to neovascularization.
AB  - Lung morphogenesis is dependent on interactions between mesenchymal and
      epithelial cells. We have previously demonstrated that inhibition of
      neovascularization by endothelial monocyte-activating polypeptide (EMAP) II also
      attenuates fetal lung morphogenesis in vivo, and hypothesized that epithelial
      mesenchymal interactions are regulated by vascular signals. To address this
      postulate, we evaluated the formation of epithelial cysts in vitro and assessed
      this complex interaction through: (i) identification of vascular formation in
      vitro; (ii) assessment of the effect of selective vascular inhibition on cell
      viability, proliferation, and cellular interactions as measured by epithelial
      cyst formation; and (iii) examination of whether there is an interdependent
      relationship between epithelial and mesenchymal cells and a vascular mediator's
      protein expression. Vascular networks in vitro formed in direct relationship to
      the presence of epithelial cysts. Disruption of the vasculature by delivery of a
      selective antiangiogenic protein EMAP II was associated with disruption of
      epithelial cyst formation. Lastly, control of the vascular formation regulatory
      protein EMAP II is a direct result of epithelial-mesenchymal cell interactions.
      These findings suggest that vascular formation modulates and is modulated by the
      normal cellular communication and interactions that direct lung morphology.

PMID- 14672914
TI  - Nerve growth factor and substance P regulation in nasal sensory neurons after
      toluene diisocyanate exposure.
AB  - Toluene diisocyanate (TDI) exposure produces rhinitis and nasal irritation, and
      increases the synthesis and release of substance P (SP) from airway sensory
      nerves. The mechanism leading to enhanced SP production following irritant
      inhalation remains unclear, but may involve actions of nerve growth factor (NGF).
      NGF binds trkA receptors located on sensory nerve terminals. Activation of trkA
      receptors initiates kinase-signaling cascades, which ultimately may increase SP.
      However, the effects of inhaled irritants on NGF release are not known. In this
      study, NGF levels in nasal lavages were examined following instillation of 10%
      TDI into both nasal cavities. NGF was significantly increased 2, 6, 12, and 24 h
      after TDI exposure compared with controls. The increase in NGF preceded the
      neuronal and mucosal increases in SP. Pretreatment with K252a, a nonselective
      tyrosine-kinase inhibitor, prevented the increase in SP-immunoreactivity in TG
      neurons and epithelial nerve fibers and the inflammatory response to TDI
      exposure. Because NGF binds to trkA tyrosine-kinase receptors, the NGF released
      during TDI exposure may mediate SP upregulation in airway sensory neurons,
      innervating the nasal cavity.

PMID- 14672915
TI  - Stromal-derived factor-1alpha/CXCL12-CXCR 4 axis is involved in the dissemination
      of NSCLC cells into pleural space.
AB  - Malignant pleural effusion (PE) is one of the poor prognostic factors in non
      small cell lung cancer (NSCLC), and the detailed mechanism of the malignant PE
      formation is not fully elucidated. Recently, CXCR4, a receptor for chemokine
      stromal-derived factor-1alpha (SDF-1alpha) that can induce chemotaxis of cells,
      was reported to be expressed on NSCLC. In this study, we hypothesized that the
      SDF-1alpha/CXCR4 axis may be involved in the dissemination of malignant cells
      into pleural space, and investigated its expression, function, and signaling
      pathway using NSCLC cell lines and clinical samples from 43 patients with NSCLC
      with malignant PE. We found functional expression of CXCR4 on NSCLC cell lines,
      and also found that SDF-1alpha could induce migration via phosphatidylinositol 3
      (PI-3) kinase- and p44/42 mitogen-activated protein kinase-dependent manner. The
      SDF-1alpha levels in malignant PE were significantly higher than those in
      transudate PE and showed a significant positive correlation with PE volumes. The
      sensitivity and specificity for prediction of recurrence of malignant PE was
      61.5% and 83.3%, respectively (cutoff SDF-1alpha = 2,500 ng/ml), and better than
      those using pH of PE. Cancer cells in malignant PE expressed CXCR4, and
      mesothelial cells of the pleura stained positive for SDF-1alpha. The SDF
      1alpha/CXCR4 axis is involved in the dissemination of NSCLC cells into pleural
      space.

PMID- 14672916
TI  - Interactions of influenza A virus with sialic acids present on porcine surfactant
      protein D.
AB  - Pigs can be infected with both human and avian influenza A virus (IAV) strains
      and are therefore considered to be important intermediates in the emergence of
      new IAV strains due to mixing of viral genes derived from human, avian, or
      porcine influenza viruses. These reassortant strains may have potential to cause
      pandemic influenza outbreaks in humans. The innate immune response against IAV
      plays a significant role in containment of IAV in the airways. We studied the
      interactions of IAV with porcine surfactant protein D (pSP-D), an important
      component of this first line defense system. Hemagglutination inhibition analysis
      shows that the distinct interactions of pSP-D with IAV mediated by the N-linked
      carbohydrate moiety in the carbohydrate recognition domain of pSP-D depend on the
      terminal sialic acids (SAs) present on this carbohydrate. Analysis by both lectin
      staining and by cleavage with linkage-specific sialidases shows that the
      carbohydrate of pSP-D is exclusively sialylated with alpha(2,6)-linked SAs, in
      contrast to surfactant protein A, which contains both alpha(2,3)- and alpha(2,6)
      linked SAs on its N-linked carbohydrate. Enzymatic modification of the SA
      linkages present on pSP-D demonstrates that the type of SA-linkage is important
      for its hemagglutination-inhibitory activity, and correlates with receptor
      binding specificity of the IAV strains. The SAs present on pSP-D appear
      especially important for interactions with poorly glycosylated IAV strains. It
      remains to be elucidated to what extent the unique sialylation profile of pSP-D
      is involved in host range control of IAV in pigs, and whether it facilitates
      adaptation of avian or human IAV strains that can contribute to the production of
      reassortant strains in pigs.

PMID- 14672917
TI  - Differential translational efficiency of ENaC subunits during lung development.
AB  - The amiloride-sensitive epithelial Na(+) channel (ENaC), the rate-limiting step
      in epithelial Na(+) transport, consists of three subunits: alpha, beta, and
      gamma. The abundance of mRNA encoding the alpha-subunit far surpasses the amount
      for other subunits, and considerably exceeds the predicted subunit protein
      stoichiometry. We evaluated 5'-untranslated region (UTR) expression and found
      that fetal rat lung uses alternative 5'UTRs for alpha-ENaC during development.
      Sucrose density gradient analysis of postnuclear supernatants from fetal rat lung
      homogenates demonstrated that all three ENaC subunits were associated with high
      molecular weight polysomes, indicating active translation of the mRNAs, but
      translational efficiency was much lower for the alpha-subunit. Sucrose density
      gradient distributions were comparable for the endogenously expressed alpha-ENaC
      5'UTRs in rat lung at Fetal Day 20 or Postnatal Day 1 using Northern analysis.
      Although birth resulted in a global decrease in lung mRNA translation, the
      loading of ribosomes on ENaC subunit mRNAs was largely unaffected. Evaluation of
      cytokeratin 18 and vimentin mRNAs in these gradients suggested a cell-specific
      effect. We conclude that there are different translational efficiencies for ENaC
      subunits and that perinatal processes globally modulate lung mRNA translation.

PMID- 14672918
TI  - p38mapk and MEK1/2 inhibition contribute to cellular oxidant injury after
      hypoxia.
AB  - Lung epithelial cells produce increased reactive oxygen species (ROS) after
      hypoxia exposure, and they are more susceptible after hypoxia to injury by agents
      that generate superoxide [O2-; e.g., 2,3-dimethoxy-1,4-naphthoquinone (DMNQ)].
      Cellular GSH and MnSOD both decrease in hypoxic lung epithelial cells, altering
      the redox state. Because ROS participate in signaling pathways involved in cell
      death or survival, we tested the hypothesis that mitogen-activated protein
      kinases (MAPK) were involved in a protective response against cellular injury
      during reoxygenation. Human lung epithelial A549 cells were incubated in hypoxia
      (<1% O2 for 24 h) and then reoxygenated by return to air. p38mapk and MKK3
      phosphorylation both decreased after hypoxia. During reoxygenation, cells were
      incubated with DMNQ (0-50 microM), a redox cycling quinone that produces O2-.
      Hypoxia preexposure significantly increased epithelial cell lysis resulting from
      DMNQ. Addition of the p38mapk inhibitors SB-202190 or SB-203580 markedly
      increased cytotoxicity, as did the mitogen/extracellular signal-regulated kinase
      (MEK) 1/2 inhibitor PD-98059 (all 10 microM), suggesting a protective effect of
      downstream molecules activated by the kinases. Transfection of A549 cells with a
      dominant active MKK3 plasmid (MKK3[Glu]) partially inhibited cytolysis resulting
      from DMNQ, whereas the inactive MKK3 plasmid (MKK3[Ala]) had less evident
      protective effects. Stress-related signaling pathways in epithelial cells are
      modulated by hypoxia and confer protection from reoxygenation, since hypoxia and
      chemical inhibition of p38mapk and MEK1/2 similarly increase cytolysis resulting
      from O2-.

PMID- 14672919
TI  - Contribution of oxygen radicals to altered NO-dependent pulmonary vasodilation in
      acute and chronic hypoxia.
AB  - Chronic hypoxia (CH) increases pulmonary arterial endothelial nitric oxide (NO)
      synthase (NOS) expression and augments endothelium-derived nitric oxide (EDNO)
      dependent vasodilation, whereas vasodilatory responses to exogenous NO are
      attenuated in CH rat lungs. We hypothesized that reactive oxygen species (ROS)
      inhibit NO-dependent pulmonary vasodilation following CH. To test this
      hypothesis, we examined responses to the EDNO-dependent vasodilator endothelin-1
      (ET-1) and the NO donor S-nitroso-N-acetyl penicillamine (SNAP) in isolated lungs
      from control and CH rats in the presence or absence of ROS scavengers under
      normoxic or hypoxic ventilation. NOS was inhibited in lungs used for SNAP
      experiments to eliminate influences of endogenously produced NO. Additionally,
      dichlorofluorescein (DCF) fluorescence was measured as an index of ROS levels in
      isolated pressurized small pulmonary arteries from each group. We found that
      acute hypoxia increased DCF fluorescence and attenuated vasodilatory responses to
      ET-1 in lungs from control rats. The addition of ROS scavengers augmented ET-1
      induced vasodilation in lungs from both groups during hypoxic ventilation. In
      contrast, upon NOS inhibition, DCF fluorescence was elevated and SNAP-induced
      vasodilation diminished in arteries from CH rats during normoxia, whereas acute
      hypoxia decreased DCF fluorescence, which correlated with augmented reactivity to
      SNAP in both groups. ROS scavengers enhanced SNAP-induced vasodilation in
      normoxia-ventilated lungs from CH rats similar to effects of hypoxic ventilation.
      We conclude that inhibition of NOS during normoxia leads to greater ROS
      generation in lungs from both control and CH rats. Furthermore, NOS inhibition
      reveals an effect of acute hypoxia to diminish ROS levels and augment NO-mediated
      pulmonary vasodilation.

PMID- 14672920
TI  - Hepatocyte growth factor inhibits the formation of the basement membrane of
      alveolar epithelial cells in vitro.
AB  - Hepatocyte growth factor (HGF) is a pulmotrophic factor for the regeneration of
      injured pulmonary tissue. We investigated the role of HGF in basement membrane
      formation during wound healing by immortalized alveolar type II epithelial cells
      that could form a continuous basement membrane when they were cultured on
      collagen fibrils in the presence of entactin-contaminated laminin-1. Cells
      cultured with 5.0 ng/ml HGF neither formed a continuous basement membrane on
      collagen fibrils nor maintained a continuous basement membrane architecture on a
      basement membrane substratum. The cells showed increased secretion of matrix
      metalloproteinase-9 and urokinase-type plasminogen activator, and the HGF-induced
      inhibition of basement membrane formation was attenuated by addition of 200 ng/ml
      tissue inhibitor of matrix metalloproteinase-1. Cells sequentially exposed to HGF
      and 1.0 ng/ml transforming growth factor-beta1 had enhanced basement membrane
      formation compared with those receiving these reagents in the reverse order or
      concurrently. HGF simultaneously stimulated proliferation and migration of the
      cells so that it advanced wound closure on the basement membrane substratum. The
      present results indicate that the role of HGF in wound healing is the stimulation
      of reepithelization, but this factor may also contribute to the degradation of
      the basement membrane.

PMID- 14672921
TI  - VE-cadherin-p120 interaction is required for maintenance of endothelial barrier
      function.
AB  - Interaction of p120 with juxtamembrane domain (JMD) of VE-cadherin has been
      implicated in regulation of endothelial cell-cell adhesion. We used a number of
      approaches to alter the level of p120 available for binding to VE-cadherin as a
      means to investigate the role of p120-VE-cadherin interaction in regulation of
      barrier function in confluent endothelial monolayers. Expression of an epitope
      tagged fragment corresponding to JMD of VE-cadherin resulted in a decrease in
      endothelial barrier function as assessed by changes in albumin clearance and
      electrical resistance. Binding of JMD-Flag to p120 resulted in a decreased level
      of p120. In addition to decreasing p120 level, expression of JMD also decreased
      level of VE-cadherin. Expression of JMD also caused an increase in MLC
      phosphorylation and rearrangement of actin cytoskeleton, which, coupled with
      decreased cadherin, can contribute to loss of barrier function. Reducing p120 by
      siRNA resulted in a decrease in VE-cadherin, whereas increasing the level of p120
      increased the level of VE-cadherin, demonstrating that p120 regulates the level
      of VE-cadherin. Overexpression of p120 was, however, associated with decreased
      barrier function and rearrangement of the actin cytoskeleton. Interestingly,
      expression of p120 was able to inhibit thrombin-induced increases in MLC
      phosphorylation, suggesting that p120 inhibits activation of Rho/Rho kinase
      pathway in endothelial cells. Excess p120 also prevented JMD-induced increases in
      MLC phosphorylation, correlating this phosphorylation with Rho/Rho kinase
      pathway. These findings show p120 plays a major role in regulating endothelial
      barrier function, as either a decrease or increase of p120 resulted in disruption
      of permeability across cell monolayers.

PMID- 14672922
TI  - Capacitative calcium entry and TRPC channel proteins are expressed in rat distal
      pulmonary arterial smooth muscle.
AB  - Mammalian homologs of transient receptor potential (TRP) genes in Drosophila
      encode TRPC proteins, which make up cation channels that play several putative
      roles, including Ca2+ entry triggered by depletion of Ca2+ stores in endoplasmic
      reticulum (ER). This capacitative calcium entry (CCE) is thought to replenish
      Ca2+ stores and contribute to signaling in many tissues, including smooth muscle
      cells from main pulmonary artery (PASMCs); however, the roles of CCE and TRPC
      proteins in PASMCs from distal pulmonary arteries, which are thought to be the
      major site of pulmonary vasoreactivity, remain uncertain. As an initial test of
      the possibility that TRPC channels contribute to CCE and Ca2+ signaling in distal
      PASMCs, we measured [Ca2+]i by fura-2 fluorescence in primary cultures of
      myocytes isolated from rat intrapulmonary arteries (>4th generation). In cells
      perfused with Ca2+-free media containing cyclopiazonic acid (10 microM) and
      nifedipine (5 microM) to deplete ER Ca2+ stores and block voltage-dependent Ca2+
      channels, restoration of extracellular Ca2+ (2.5 mM) caused marked increases in
      [Ca2+]i whereas MnCl2 (200 microM) quenched fura-2 fluorescence, indicating CCE.
      SKF-96365, LaCl3, and NiCl2, blocked CCE at concentrations that did not alter
      Ca2+ responses to 60 mM KCl (IC50 6.3, 40.4, and 191 microM, respectively). RT
      PCR and Western blotting performed on RNA and protein isolated from distal
      intrapulmonary arteries and PASMCs revealed mRNA and protein expression for
      TRPC1, -4, and -6, but not TRPC2, -3, -5, or -7. Our results suggest that CCE
      through TRPC-encoded Ca2+ channels could contribute to Ca2+ signaling in myocytes
      from distal intrapulmonary arteries.

PMID- 14672923
TI  - Regulation of macrophage cyclooxygenase-2 gene expression by modifications of
      histone H3.
AB  - Some transcription factors involved in the regulation of cyclooxygenase 2 (COX-2)
      expression in macrophage, including NF-kappaB, interact with p300, which contains
      histone acetyltransferase (HAT) enzyme complex. Chromatin structure is regulated
      by modifying enzymes, including HAT, and plays an important role in eukaryotic
      gene regulation through histone modification. We hypothesized that changes in
      chromatin structure related to phosphorylation and acetylation of histone H3
      adjacent to key DNA binding sequence motif in the COX-2 promoter contribute to
      COX-2 gene activation in macrophages. Sodium butyrate (NaBT) is a short-chain
      fatty acid that possesses histone deacetyltransferase-inhibiting activity. Our
      data show that NaBT accentuates LPS-induced COX-2 gene expression at a
      transcriptional level, even though NaBT alone does not induce the COX-2 gene
      expression. Using a chromatin immunoprecipitation assay, we showed that
      costimulation of RAW 264.7 cells with NaBT and LPS synergistically increases COX
      2 gene expression through both acetylation and phosphorylation of histone H3 at
      the promoter site. Our data show that NaBT accentuates LPS-induced COX-2 gene
      expression through MAP kinase-dependent increase of phosphorylation and
      acetylation of histone H3 at the COX-2 promoter site. These data indicate that
      posttranslational modification of histone H3 has a major effect on COX-2 gene
      expression by macrophages.

PMID- 14672924
TI  - Myosin light chain phosphorylation and pulmonary endothelial cell
      hyperpermeability in burns.
AB  - Major cutaneous burns result in not only localized tissue damage but broad
      systemic inflammation causing organ system damage distal to the burn site. It is
      well recognized that many problems result from the release of inflammatory
      mediators that target vascular endothelial cells, causing organ dysfunction. The
      pulmonary microvessels are particularly susceptible to functional abnormalities
      as a direct consequence of exposure to burn-induced inflammatory mediators.
      Traditional therapeutic intervention is quite often ineffective in treating burn
      patients suffering from systemic problems. A possible explanation for this
      ineffectiveness may be that because so many mediators are released, supposedly
      activating numerous signaling cascades that interact with each other, targeting
      of upstream factors in these cascades on an individual basis becomes futile.
      Therefore, if an end-point effector responsible for endothelial dysfunction
      following burn injury could be identified, it may present a target for
      intervention. In this study, we identified phosphorylation of myosin light chain
      (MLC) as a required element of burn plasma-induced hyperpermeability across rat
      lung microvascular endothelial cell monolayers. In addition, pharmacological
      inhibition of myosin light chain kinase (MLCK) and Rho kinase as well as
      transfection of MLCK-inhibiting peptide blocked actin stress fiber formation and
      MLC phosphorylation in response to burn plasma. The results suggest that blocking
      MLC phosphorylation may provide therapeutic intervention in burn patients with
      the goal of alleviating systemic inflammation-induced endothelial dysfunction.

PMID- 14672925
TI  - Formation and stability of S-nitrosothiols in RAW 264.7 cells.
AB  - S-Nitrosothiols have been suggested to be mediators of many nitric oxide
      dependent processes, including apoptosis and vascular relaxation. Thiol
      nitrosation is a poorly understood process in vivo, and the mechanisms by which
      nitric oxide can be converted into a nitrosating agent have not been established.
      There is a discrepancy between the suggested biological roles of nitric oxide and
      its known chemical and physical properties. In this study, we have examined the
      formation of S-nitrosothiols in lipopolysaccharide-treated RAW 264.7 cells. This
      treatment generated 17.4 +/- 1.0 pmol/mg of protein (means +/- SE, n =27) of
      intracellular S-nitrosothiol that slowly decayed over several hours. S
      Nitrosothiol formation depended on the formation of nitric oxide and not on the
      presence of nitrite. Extracellular thiols were nitrosated by cell-generated
      nitric oxide. Oxygenated ferrous hemoglobin inhibited the formation of S
      nitrosothiol, indicating the nitrosation occurred more slowly than diffusion. We
      discuss several mechanisms for S-nitrosothiol formation and conclude that the
      nitrosation propensity of nitric oxide is a freely diffusible element that is not
      constrained within an individual cell and that both nitric oxide per se and
      nitric oxide-derived nitrosating agents are able to diffuse across cell
      membranes. To achieve intracellular localization of the nitrosation reaction,
      mechanisms must be invoked that do not involve the formation of nitric oxide as
      an intermediate.

PMID- 14672926
TI  - The YefM antitoxin defines a family of natively unfolded proteins: implications
      as a novel antibacterial target.
AB  - Although natively unfolded proteins are being observed increasingly, their
      physiological role is not well understood. Here, we demonstrate that the
      Escherichia coli YefM protein is a natively unfolded antitoxin, lacking secondary
      structure even at low temperature or in the presence of a stabilizing agent. This
      conformation of the protein is suggested to have a key role in its physiological
      regulatory activity. Because of the unfolded state of the protein, a linear
      determinant rather than a conformational one is presumably being recognized by
      its toxin partner, YoeB. A peptide array technology allowed the identification
      and validation of such a determinant. This recognition element may provide a
      novel antibacterial target. Indeed, a pair-constrained bioinformatic analysis
      facilitated the definite determination of novel YefM-YoeB toxin-antitoxin systems
      in a large number of bacteria including major pathogens such as Staphylococcus
      aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis. Taken together,
      the YefM protein defines a new family of natively unfolded proteins. The
      existence of a large and conserved group of proteins with a clear physiologically
      relevant unfolded state serves as a paradigm to understand the structural basis
      of this state.

PMID- 14672927
TI  - Effects of vaccine strain mutations in domain V of the internal ribosome entry
      segment compared in the wild type poliovirus type 1 context.
AB  - Initiation of poliovirus (PV) protein synthesis is governed by an internal
      ribosome entry segment structured into several domains including domain V, which
      is accepted to be important in PV neurovirulence because it harbors an
      attenuating mutation in each of the vaccine strains developed by A. Sabin. To
      better understand how these single point mutations exert their effects, we placed
      each of them into the same genomic context, that of PV type 1. Only the mutation
      equivalent to the Sabin type 3 strain mutation resulted in significantly reduced
      viral growth both in HeLa and neuroblastoma cells. This correlated with poor
      translation efficiency in vitro and could be explained by a structural
      perturbation of the domain V of the internal ribosome entry segment, as evidenced
      by RNA melting experiments. We demonstrated that reduced cell death observed
      during infection by this mutant is due to the absence of inhibition of host cell
      translation. We confirmed that this shut-off is correlated principally with
      cleavage of eIF4GII and not eIF4GI and that this cleavage is significantly
      impaired in the case of the defective mutant. These data support the previously
      reported conclusion that the 2A protease has markedly different affinities for
      the two eIF4G isoforms.

PMID- 14672928
TI  - Vif overcomes the innate antiviral activity of APOBEC3G by promoting its
      degradation in the ubiquitin-proteasome pathway.
AB  - Viruses must overcome diverse intracellular defense mechanisms to establish
      infection. The Vif (virion infectivity factor) protein of human immunodeficiency
      virus 1 (HIV-1) acts by overcoming the antiviral activity of APOBEC3G (CEM15), a
      cytidine deaminase that induces G to A hypermutation in newly synthesized viral
      DNA. In the absence of Vif, APOBEC3G incorporation into virions renders HIV-1 non
      infectious. We report here that Vif counteracts the antiviral activity of
      APOBEC3G by targeting it for destruction by the ubiquitin-proteasome pathway. Vif
      forms a complex with APOBEC3G and enhances APOBEC3G ubiquitination, resulting in
      reduced steady-state APOBEC3G levels and a decrease in protein half-life.
      Furthermore, Vif-dependent degradation of APOBEC3G is blocked by proteasome
      inhibitors or ubiquitin mutant K48R. A mutation of highly conserved cysteines or
      the deletion of a conserved SLQ(Y/F)LA motif in Vif results in mutants that fail
      to induce APOBEC3G degradation and produce non-infectious HIV-1; however,
      mutations of conserved phosphorylation sites in Vif that impair viral replication
      do not affect APOBEC3G degradation, suggesting that Vif is important for other
      functions in addition to inducing proteasomal degradation of APOBEC3G. Vif is
      monoubiquitinated in the absence of APOBEC3G but is polyubiquitinated and rapidly
      degraded when APOBEC3G is coexpressed, suggesting that coexpression accelerates
      the degradation of both proteins. These results suggest that Vif functions by
      targeting APOBEC3G for degradation via the ubiquitin-proteasome pathway and
      implicate the proteasome as a site of dynamic interplay between microbial and
      cellular defenses.

PMID- 14672929
TI  - The quaternary structure of the Saccharomyces cerevisiae succinate dehydrogenase.
      Homology modeling, cofactor docking, and molecular dynamics simulation studies.
AB  - Succinate dehydrogenases and fumarate reductases are complex mitochondrial or
      bacterial respiratory chain proteins with remarkably similar structures and
      functions. Succinate dehydrogenase oxidizes succinate and reduces ubiquinone
      using a flavin adenine dinucleotide cofactor and iron-sulfur clusters to
      transport electrons. A model of the quaternary structure of the tetrameric
      Saccharomyces cerevisiae succinate dehydrogenase was constructed based on the
      crystal structures of the Escherichia coli succinate dehydrogenase, the E. coli
      fumarate reductase, and the Wolinella succinogenes fumarate reductase. One FAD
      and three iron-sulfur clusters were docked into the Sdh1p and Sdh2p catalytic
      dimer. One b-type heme and two ubiquinone or inhibitor analog molecules were
      docked into the Sdh3p and Sdh4p membrane dimer. The model is consistent with
      numerous experimental observations. The calculated free energies of inhibitor
      binding are in excellent agreement with the experimentally determined inhibitory
      constants. Functionally important residues identified by mutagenesis of the SDH3
      and SDH4 genes are located near the two proposed quinone-binding sites, which are
      separated by the heme. The proximal quinone-binding site, located nearest the
      catalytic dimer, has a considerably more polar environment than the distal site.
      Alternative low energy conformations of the membrane subunits were explored in a
      molecular dynamics simulation of the dimer embedded in a phospholipid bilayer.
      The simulation offers insight into why Sdh4p Cys-78 may be serving as the second
      axial ligand for the heme instead of a histidine residue. We discuss the possible
      roles of heme and of the two quinone-binding sites in electron transport.

PMID- 14672930
TI  - Identification of the heme axial ligands in the cytochrome b562 of the
      Saccharomyces cerevisiae succinate dehydrogenase.
AB  - Succinate dehydrogenase (SDH) plays a key role in energy generation by coupling
      the oxidation of succinate to the reduction of ubiquinone in the mitochondrial
      electron transport chain. The Saccharomyces cerevisiae SDH is composed of a
      catalytic dimer of the Sdh1p and Sdh2p subunits containing flavin adenine
      dinucleotide (FAD) and iron-sulfur clusters and a heme b-containing membrane
      anchoring domain comprised of the Sdh3p and Sdh4p subunits. We systematically
      mutated all the histidine and cysteine residues in Sdh3p and Sdh4p to identify
      the residues involved in axial heme ligation. The mutants were characterized for
      growth on a non-fermentable carbon source, for enzyme assembly, for succinate
      dependent quinone reduction, for heme b content, and for heme spectral
      properties. Mutation of Sdh3p His-46 or His-113 leads to a marked reduction in
      the catalytic efficiency of the enzyme for quinone reduction, suggesting that
      these residues form part of a quinone-binding site. We identified Sdh3p His-106
      and Sdh4p Cys-78 as the most probable axial ligands for cytochrome b(562).
      Replacement of His-106 or Cys-78 with an alanine residue leads to a marked
      reduction in cytochrome b(562) content and to altered heme spectral
      characteristics that are consistent with a direct perturbation of heme b
      environment. This is the first identification of a cysteine residue serving as an
      axial ligand for heme b in the SDH family of enzymes. Loss of cytochrome b(562)
      has no effect on enzyme assembly and quinone reduction; the role of the heme in
      enzyme structure and function is discussed.

PMID- 14672931
TI  - X-ray structures of the leucine-binding protein illustrate conformational changes
      and the basis of ligand specificity.
AB  - The periplasmic leucine-binding protein is the primary receptor for the leucine
      transport system in Escherichia coli. We report here the structure of an open
      ligand-free form solved by molecular replacement and refined at 1.5-A resolution.
      In addition, two closed ligand-bound structures of the same protein are
      presented, a phenylalanine-bound form at 1.8 A and a leucine-bound structure at a
      nominal resolution of 2.4 A. These structures show the basis of this protein's
      ligand specificity, as well as illustrating the conformational changes that are
      associated with ligand binding. Comparison with earlier structures provides
      further information about solution conformations, as well as the different
      specificity of the closely related leucine/isoleucine/valine-binding protein.

PMID- 14672932
TI  - The regulated association of Cdt1 with minichromosome maintenance proteins and
      Cdc6 in mammalian cells.
AB  - Chromosomal DNA replication requires the recruitment of the six-subunit
      minichromosome maintenance (Mcm) complex to chromatin through the action of Cdc6
      and Cdt1. Although considerable work has described the functions of Cdc6 and Cdt1
      in yeast and biochemical systems, evidence that their mammalian counterparts are
      subject to distinct regulation suggests the need to further explore the molecular
      relationships involving Cdc6 and Cdt1. Here we demonstrate that Cdc6 and Cdt1 are
      mutually dependent on one another for loading Mcm complexes onto chromatin in
      mammalian cells. The association of Cdt1 with Mcm2 is regulated by cell growth.
      Mcm2 prepared from quiescent cells associates very weakly with Cdt1, whereas Mcm2
      from serum-stimulated cells associates with Cdt1 much more efficiently. Cdc6,
      which normally accumulates as cells progress from quiescence into G(1), is
      capable of inducing the binding of Mcm2 to Cdt1 when ectopically expressed in
      quiescent cells. We further show that Cdc6 physically associates with Cdt1 via
      its N-terminal noncatalytic domain, a region we had previously shown to be
      essential for Cdc6 function. Cdt1 activity is inhibited by the geminin protein,
      and we provide evidence that the mechanism of this inhibition involves blocking
      the binding of Cdt1 to both Mcm2 and Cdc6. These results identify novel molecular
      functions for both Cdc6 and geminin in controlling the association of Cdt1 with
      other components of the replication apparatus and indicate that the association
      of Cdt1 with the Mcm complex is controlled as cells exit and reenter the cell
      cycle.

PMID- 14672933
TI  - Annexin A2 is a novel RNA-binding protein.
AB  - Annexin A2 (ANXA2) is a Ca(2+)-binding protein that is up-regulated in virally
      transformed cell lines and in human tumors. Here, we show that ANXA2 binds
      directly to both ribonucleotide homopolymers and human c-myc RNA. ANXA2 was shown
      to bind specifically to poly(G) with high affinity (K(d) = 60 nM) and not to
      poly(A), poly(C), or poly(U). The binding of ANXA2 to poly(G) required Ca(2+)
      (A(50%) = 10 microM). The presence of RNA in the immunoprecipitates of ANXA2
      isolated from HeLa cells established that ANXA2 formed a ribonucleoprotein
      complex in vivo. Sucrose gradient analysis showed that ANXA2 associates with
      ribonucleoprotein complexes and not with polyribosomes. Reverse transcriptase-PCR
      identified c-myc mRNA as a component of the ribonucleoprotein complex formed by
      ANXA2 in vivo, and binding studies confirmed a direct interaction between ANXA2
      and c-myc mRNA. Transfection of LNCaP cells with the ANXA2 gene resulted in the
      up-regulation of c-Myc protein. These findings identify ANXA2 as a Ca(2+)
      dependent RNA-binding protein that interacts with the mRNA of the nuclear
      oncogene, c-myc.

PMID- 14672934
TI  - The crystal structure of CCG1/TAF(II)250-interacting factor B (CIB).
AB  - The general transcription initiation factor TFIID and its interactors play
      critical roles in regulating the transcription from both naked and chromatin DNA.
      We have isolated a novel TFIID interactor that we denoted as CCG1/TAF(II)250
      interacting factor B (CIB). We show here that CIB activates transcription. To
      further understand the function of this protein, we determined its crystal
      structure at 2.2-Angstroms resolution. The tertiary structure of CIB reveals an
      alpha/beta-hydrolase fold that resembles structures in the prokaryotic alpha/beta
      hydrolase family proteins. It is not similar in structure or primary sequence to
      any eukaryotic transcription or chromatin factors that have been reported to
      date. CIB possesses a conserved catalytic triad that is found in other alpha/beta
      hydrolases, and our in vitro studies confirmed that it bears hydrolase activity.
      However, CIB differs from other alpha/beta-hydrolases in that it lacks a binding
      site excursion, which facilitates the substrate selectivity of the other
      alpha/beta-hydrolases. Further functional characterization of CIB based on its
      tertiary structure and through biochemical studies may provide novel insights
      into the mechanisms that regulate eukaryotic transcription.

PMID- 14672935
TI  - Specificity and phenetic relationships of iron- and manganese-containing
      superoxide dismutases on the basis of structure and sequence comparisons.
AB  - The iron- and manganese-containing superoxide dismutases (Fe/Mn-SOD) share the
      same chemical function and spatial structure but can be distinguished according
      to their modes of oligomerization and their metal ion specificity. They appear as
      homodimers or homotetramers and usually require a specific metal for activity. On
      the basis of 261 aligned SOD sequences and 12 superimposed x-ray structures, two
      phenetic trees were constructed, one sequence-based and the other structure
      based. Their comparison reveals the imperfect correlation of sequence and
      structural changes; hyperthermophilicity requires the largest sequence
      alterations, whereas dimer/tetramer and manganese/iron specificities are induced
      by the most sizable structural differences within the monomers. A systematic
      investigation of sequence and structure characteristics conserved in all aligned
      SOD sequences or in subsets sharing common oligomeric and/or metal specificities
      was performed. Several residues were identified as guaranteeing the common
      function and dimeric conformation, others as determining the tetramer formation,
      and yet others as potentially responsible for metal specificity. Some form cation
      pi interactions between an aromatic ring and a fully or partially positively
      charged group, suggesting that these interactions play a significant role in the
      structure and function of SOD enzymes. Dimer/tetramer- and iron/manganese
      specific fingerprints were derived from the set of conserved residues; they can
      be used to propose selected residue substitutions in view of the experimental
      validation of our in silico derived hypotheses.

PMID- 14672936
TI  - Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular
      development.
AB  - Mammalian Fbw7 (also known as Sel-10, hCdc4, or hAgo) is the F-box protein
      component of an SCF (Skp1-Cul1-F-box protein-Rbx1)-type ubiquitin ligase, and the
      mouse Fbw7 is expressed prominently in the endothelial cell lineage of embryos.
      We generated mice deficient in Fbw7 and found that the embryos died in utero at
      embryonic day 10.5-11.5, manifesting marked abnormalities in vascular
      development. Vascular remodeling was impaired in the brain and yolk sac, and the
      major trunk veins were not formed. In vitro para-aortic splanchnopleural explant
      cultures from Fbw7(-/-) embryos also manifested an impairment of vascular network
      formation. Notch4, which is the product of the proto-oncogene Int3 and an
      endothelial cell-specific mammalian isoform of Notch, accumulated in Fbw7(-/-)
      embryos, resulting in an increased expression of Hey1, which encodes a
      transcriptional repressor that acts downstream of Notch signaling and is
      implicated in vascular development. Expression of Notch1, -2, or -3 or of cyclin
      E was unaffected in Fbw7(-/-) embryos. Mammalian Fbw7 thus appears to play an
      indispensable role in negative regulation of the Notch4-Hey1 pathway and is
      required for vascular development.

PMID- 14672937
TI  - Alternative start sites in the Saccharomyces cerevisiae GLR1 gene are responsible
      for mitochondrial and cytosolic isoforms of glutathione reductase.
AB  - To combat oxidative damage, eukaryotic cells have evolved with numerous anti
      oxidant factors that are often distributed between cytosolic and mitochondrial
      pools. Glutathione reductase, which regenerates the reduced form of glutathione,
      represents one such anti-oxidant factor, yet nothing is known regarding the
      partitioning of this enzyme within the cell. Using the bakers' yeast
      Saccharomyces cerevisiae as a model, we provide evidence that a single gene,
      namely GLR1, encodes both the mitochondrial and cytosolic forms of glutathione
      reductase. A deletion in GLR1 drastically increases levels of oxidized
      glutathione in these two subcellular compartments. The GLR1 gene has two inframe
      start codons that are both used as translation initiation sites. Translation from
      the first codon generates the mitochondrial form that includes a mitochondrial
      targeting signal, whereas translation from the second codon produces the
      cytosolic form that lacks this sequence. Our results indicate that the sequence
      context of the two AUG codons influences the efficiency of translation initiation
      at each site, which in turn affects the relative levels of cytosolic and
      mitochondrial Glr1p. This method of subcellular distribution of glutathione
      reductase may be conserved in mammalian cells as well.

PMID- 14672938
TI  - Chromatin contributes to structural integrity of promyelocytic leukemia bodies
      through a SUMO-1-independent mechanism.
AB  - Promyelocytic leukemia (PML) protein is implicated in transcriptional regulation,
      apoptosis, DNA repair, and tumor suppression. It is not known, however, whether
      PML and other components of PML bodies function within the vicinity of the bodies
      or elsewhere in the nucleoplasm. In this study, we demonstrate that chromatin
      organization around PML bodies influences their morphology, dynamics, and
      structural integrity by a SUMO-1-independent mechanism. Following transcriptional
      inhibition and during early apoptosis, chromatin retracts from the periphery of
      PML bodies, coinciding with the formation of new PML-containing structures
      through fission of supramolecular PML-containing microbodies. Both fission and
      fusion of microbodies with parental PML bodies indicate a loss of structural
      integrity of the bodies, dependent on the state of the surrounding chromatin.
      This is supported by the observation that treatment of live cells with DNase I
      could reproduce the structural instability of PML bodies. In addition, PML
      bodies, which are normally surrounded by chromatin and are positionally stable,
      become more dynamic following these treatments, presumably due to the loss of
      chromatin contacts. Overexpression of SUMO-1, a modification required for PML
      body formation, did not prevent PML body fission, indicating that chromatin-based
      integrity of PML body structure occurs through a SUMO-1-independent mechanism.

PMID- 14672939
TI  - Molecules mimicking Smad1 interacting with Hox stimulate bone formation.
AB  - Bone morphogenetic proteins (BMPs) induce osteoblast differentiation and bone
      formation. Smads, a group of functionally and structurally related intracellular
      effectors, mediate signaling initiated by BMPs and regulate cell definite
      commitment. Previously, we showed that Smad1 activates osteopontin and
      osteoprotegerin gene expression by dislodging Hoxc-8 from its DNA binding sites.
      A domain of Smad1, termed Smad1C, was characterized as interacting with Hoxc-8
      and then crippling its DNA-binding ability. Ectopic expression of Smad1C is able
      to bypass BMP signaling in the induction of osteoblast differentiation and bone
      formation in vitro. To test the function of Smad1C on osteogenesis in vivo, we
      generated transgenic mice in which Smad1C expression was induced with doxycycline
      and localized in bone by using a tetracycline-inducible expression system (Tet
      on) modified with a bone-specific gene promoter, type I collagen alpha1. The mice
      expressing Smad1C showed increased skeletal bone mineral density compared with
      their littermates. Bone histomorphometric analysis of mouse tibiae showed that
      Smad1C significantly increases trabecular bone area and length of trabecular
      surface covered with osteoid and up-regulates bone marker gene (OPN, Cbfa1, Col I
      alpha1, BSP, ALP) expression in vivo. Moreover, stromal cells isolated from mice
      expressing Smad1C displayed a higher potential for differentiating into
      osteoblasts than the other mice. These results indicate that Smad1C mimics BMPs
      in the induction of osteogenesis in vivo. Most important, using a high throughput
      screening assay based on mimicking Smad1C's displacement of Hoxc-8 binding to
      DNA, we identified chemical entities that exhibit bone anabolic activity in cell
      and bone organ cultures, suggesting the possibility that the compounds may be
      used as bone anabolic agents to treat bone pathologies.

PMID- 14672940
TI  - Crystal structures of the CP1 domain from Thermus thermophilus isoleucyl-tRNA
      synthetase and its complex with L-valine.
AB  - Isoleucyl-tRNA synthetase (IleRS) links tRNA(Ile) with not only its cognate
      isoleucine but also the nearly cognate valine. The CP1 domain of IleRS
      deacylates, or edits, the mischarged Val-tRNA(Ile). We determined the crystal
      structures of the Thermus thermophilus IleRS CP1 domain alone, and in its complex
      with valine at 1.8- and 2.0-A resolutions, respectively. In the complex
      structure, the Asp(328) residue, which was shown to be critical for the editing
      reaction against Val-tRNA(Ile) by a previous mutational analysis, recognizes the
      valine NH(3)(+) group. The valine side chain binding pocket is only large enough
      to accommodate valine, and the placement of an isoleucine model in this location
      revealed that the additional methylene group of isoleucine would clash with
      His(319). The H319A mutant of Escherichia coli IleRS reportedly deacylates the
      cognate Ile-tRNA(Ile) in addition to Val-tRNA(Ile), indicating that the valine
      binding mode found in this study represents that in the Val-tRNA(Ile) editing
      reaction. Analyses of the Val-tRNA(Ile) editing activities of T. thermophilus
      IleRS mutants revealed the importance of Thr(228), Thr(229), Thr(230), and
      Asp(328), which are coordinated with water molecules in the present structure.
      The structural model for the Val-adenosine moiety of Val-tRNA(Ile) bound in the
      IleRS editing site revealed some interesting differences in the substrate binding
      and recognizing mechanisms between IleRS and T. thermophilus leucyl-tRNA
      synthetase. For example, the carbonyl oxygens of the amino acids are located
      opposite to each other, relative to the adenosine ribose ring, and are
      differently recognized.

PMID- 14672941
TI  - Galectin-3 precipitates as a pentamer with synthetic multivalent carbohydrates
      and forms heterogeneous cross-linked complexes.
AB  - Galectin-3 is unique among the galectin family of animal lectins in its
      biological activities and structure. Most members of the galectin family
      including galectin-1 possess apoptotic activities, whereas galectin-3 possesses
      anti-apoptotic activity. Galectin-3 is also the only chimera type galectin and
      consists of a nonlectin N-terminal domain and a C-terminal carbohydrate-binding
      domain. Recent sedimentation equilibrium and velocity studies show that murine
      galectin-3 is a monomer in the absence and presence of LacNAc, a monovalent
      sugar. However, quantitative precipitation studies in the present report indicate
      that galectin-3 precipitates as a pentamer with a series of divalent
      pentasaccharides with terminal LacNAc residues. Furthermore, the kinetics of
      precipitation are fast, on the order of seconds. This indicates that although the
      majority of galectin-3 in solution is a monomer, a rapid equilibrium exists
      between the monomer and a small percentage of pentamer. The latter, in turn,
      precipitates with the divalent oligosaccharides, resulting in rapid conversion of
      monomer to pentamer by mass action equilibria. Mixed quantitative precipitation
      experiments and electron microscopy suggest that galectin-3 forms heterogenous,
      disorganized cross-linking complexes with the multivalent carbohydrates. This
      contrasts with galectin-1 and many plant lectins that form homogeneous, organized
      cross-linked complexes. The results are discussed in terms of the biological
      properties of galectin-3.

PMID- 14672942
TI  - Human cytosolic 3alpha-hydroxysteroid dehydrogenases of the aldo-keto reductase
      superfamily display significant 3beta-hydroxysteroid dehydrogenase activity:
      implications for steroid hormone metabolism and action.
AB  - The source of NADPH-dependent cytosolic 3beta-hydroxysteroid dehydrogenase (3beta
      HSD) activity is unknown to date. This important reaction leads e.g. to the
      reduction of the potent androgen 5alpha-dihydrotestosterone (DHT) into inactive
      3beta-androstanediol (3beta-Diol). Four human cytosolic aldo-keto reductases
      (AKR1C1-AKR1C4) are known to act as non-positional-specific 3alpha-/17beta
      /20alpha-HSDs. We now demonstrate that AKR1Cs catalyze the reduction of DHT into
      both 3alpha- and 3beta-Diol (established by (1)H NMR spectroscopy). The rates of
      3alpha- versus 3beta-Diol formation varied significantly among the isoforms, but
      with each enzyme both activities were equally inhibited by the nonsteroidal anti
      inflammatory drug flufenamic acid. In vitro, AKR1Cs also expressed substantial
      3alpha[17beta]-hydroxysteroid oxidase activity with 3alpha-Diol as the substrate.
      However, in contrast to the 3-ketosteroid reductase activity of the enzymes,
      their hydroxysteroid oxidase activity was potently inhibited by low micromolar
      concentrations of the opposing cofactor (NADPH). This indicates that in vivo all
      AKR1Cs will preferentially work as reductases. Human hepatoma (HepG2) cells
      (which lack 3beta-HSD/Delta(5-4) ketosteroid isomerase mRNA expression, but
      express AKR1C1-AKR1C3) were able to convert DHT into 3alpha- and 3beta-Diol. This
      conversion was inhibited by flufenamic acid establishing the in vivo significance
      of the 3alpha/3beta-HSD activities of the AKR1C enzymes. Molecular docking
      simulations using available crystal structures of AKR1C1 and AKR1C2 demonstrated
      how 3alpha/3beta-HSD activities are achieved. The observation that AKR1Cs are a
      source of 3beta-tetrahydrosteroids is of physiological significance because: (i)
      the formation of 3beta-Diol (in contrast to 3alpha-Diol) is virtually
      irreversible, (ii) 3beta-Diol is a pro-apoptotic ligand for estrogen receptor
      beta, and (iii) 3beta-tetrahydrosteroids act as gamma-aminobutyric acid type A
      receptor antagonists.

PMID- 14672943
TI  - Identification of crucial histidines for heme binding in the N-terminal domain of
      the heme-regulated eIF2alpha kinase.
AB  - The heme-regulated eukaryotic initiation factor-2alpha (eIF2alpha) kinase (HRI)
      regulates the initiation of protein synthesis in reticulocytes. The binding of NO
      to the N-terminal heme-binding domain (NTD) of HRI positively modulates its
      kinase activity. By utilizing UV-visible absorption, resonance Raman, EPR and CD
      spectroscopies, two histidine residues have been identified that are crucial for
      the binding of heme to the NTD. The UV-visible absorption and resonance Raman
      spectra of all the histidine to alanine mutants constructed were similar to those
      of the unmutated NTD. However, the change in the CD spectra of the NTD construct
      containing mutation of His78 to Ala (H78A) indicated loss of the specific binding
      of heme. The EPR spectrum for the ferric H78A mutant was also substantially
      perturbed. Thus, His78 is one of the axial ligands for the NTD of HRI.
      Significant changes in the EPR spectrum of the H123A mutant were also observed,
      and heme readily dissociated from both the H123A and the H78A NTD mutants,
      suggesting that His123 was also an axial heme ligand. However, the CD spectrum
      for the Soret region of the H123A mutant indicated that this mutant still bound
      heme specifically. Thus, while both His78 and His123 are crucial for stable heme
      binding, the effects of their mutations on the structure of the NTD differed.
      His78 appears to play the primary role in the specific binding of heme to the
      NTD, acting analogously to the "proximal histidine" ligand of globins, while
      His123 appears to act as the "distal" heme ligand.

PMID- 14672944
TI  - Structural basis for bisphosphonate-mediated inhibition of isoprenoid
      biosynthesis.
AB  - Farnesyl pyrophosphate synthetase (FPPS) synthesizes farnesyl pyrophosphate
      through successive condensations of isopentyl pyrophosphate with dimethylallyl
      pyrophosphate and geranyl pyrophosphate. Nitrogen-containing bisphosphonate drugs
      used to treat osteoclast-mediated bone resorption and tumor-induced hypercalcemia
      are potent inhibitors of the enzyme. Here we present crystal structures of
      substrate and bisphosphonate complexes of FPPS. The structures reveal how enzyme
      conformational changes organize conserved active site residues to exploit metal
      induced ionization and substrate positioning for catalysis. The structures
      further demonstrate how nitrogen-containing bisphosphonates mimic a carbocation
      intermediate to inhibit the enzyme. Together, these FPPS complexes provide a
      structural template for the design of novel inhibitors that may prove useful for
      the treatment of osteoporosis and other clinical indications including cancer.

PMID- 14672945
TI  - The glycolytic enzyme aldolase mediates assembly, expression, and activity of
      vacuolar H+-ATPase.
AB  - Vacuolar H(+)-ATPases (V-ATPases) are a family of highly conserved proton pumps
      that couple hydrolysis of cytosolic ATP to proton transport out of the cytosol.
      How ATP is supplied for V-ATPase-mediated hydrolysis and for coupling of proton
      transport is poorly understood. We have reported that the glycolytic enzyme
      aldolase physically associates with V-ATPase. Here we show that aldolase
      interacts with three different subunits of V-ATPase (subunits a, B, and E). The
      binding sites for the V-ATPase subunits on aldolase appear to be on distinct
      interfaces of the glycolytic enzyme. Aldolase deletion mutant cells were able to
      grow in medium buffered at pH 5.5 but not at pH 7.5, displaying a growth
      phenotype similar to that observed in V-ATPase subunit deletion mutants.
      Abnormalities in V-ATPase assembly and protein expression observed in aldolase
      deletion mutant cells could be fully rescued by aldolase complementation. The
      interaction between aldolase and V-ATPase increased dramatically in the presence
      of glucose, suggesting that aldolase may act as a glucose sensor for V-ATPase
      regulation. Taken together, these findings provide functional evidence that the
      ATP-generating glycolytic pathway is directly coupled to the ATP-hydrolyzing
      proton pump through physical interaction between aldolase and V-ATPase.

PMID- 14672946
TI  - The shedding of betaglycan is regulated by pervanadate and mediated by membrane
      type matrix metalloprotease-1.
AB  - Betaglycan is a membrane-anchored proteoglycan that binds transforming growth
      factor-beta (TGF-beta) via its core protein. A soluble form of betaglycan can be
      released by proteolytic cleavage (also known as shedding) of the membrane-bound
      form, yielding soluble betaglycan. The mechanism leading to the generation of
      soluble betaglycan is poorly understood. Because the membrane and soluble forms
      of betaglycan have opposite effects regulating the availability of TGF-beta, it
      is important to characterize the shedding of betaglycan further. Here we present
      evidence showing that in certain cell types, pervanadate, a general tyrosine
      phosphatase inhibitor, induces the release of the previously described fragment
      that encompasses almost the entire extracellular domain of betaglycan (sBG-120).
      In addition, treatment with pervanadate unveils the existence of a novel 90-kDa
      fragment (sBG-90). Noticeably, the cleavage that generates sBG-90 is mediated by
      a tissue inhibitor of metalloprotease-2-sensitive protease. Overexpression of all
      membrane type matrix metalloproteases (MT-MMPs) described to date indicates that
      MT1-MMP and MT3-MMP are endowed with ability to generate sBG-90. Furthermore, the
      patterns of expression of different MT-MMPs in the cell lines used in this study
      suggest that MT1-MMP is the protease involved in the shedding of sBG-90.
      Overexpression of MT1-MMP in COS-1 cells, which do not express detectable levels
      of this metalloprotease, confirms the feasibility of this hypothesis.
      Unexpectedly, during the course of these experiments, we observed that MT2-MMP
      decreases the levels of MT1-MMP and betaglycan. Finally, binding competition
      experiments indicate that, similar to the wild type membrane betaglycan, sBG-90
      binds the TGF-beta2 isoform with greater affinity than TGF-beta1, suggesting that
      once released, it could affect the cellular availability of TGF-beta.

PMID- 14672947
TI  - Dissection of the functional surface of an anti-insect excitatory toxin
      illuminates a putative "hot spot" common to all scorpion beta-toxins affecting
      Na+ channels.
AB  - Scorpion beta-toxins affect the activation of voltage-sensitive sodium channels
      (NaChs). Although these toxins have been instrumental in the study of channel
      gating and architecture, little is known about their active sites. By using an
      efficient system for the production of recombinant toxins, we analyzed by point
      mutagenesis the entire surface of the beta-toxin, Bj-xtrIT, an anti-insect
      selective excitatory toxin from the scorpion Buthotus judaicus. Each toxin mutant
      was purified and analyzed using toxicity and binding assays, as well as by
      circular dichroism spectroscopy to discern the differences among mutations that
      caused structural changes and those that specifically affected bioactivity. This
      analysis highlighted a functional discontinuous surface of 1405 A(2), which was
      composed of a number of non-polar and three charged amino acids clustered around
      the main alpha-helical motif and the C-tail. Among the charged residues, Glu(30)
      is a center of a putative "hot spot" in the toxin-receptor binding-interface and
      is shielded from bulk solvent by a hydrophobic "gasket" (Tyr(26) and Val(34)).
      Comparison of the Bj-xtrIT structure with that of other beta-toxins that are
      active on mammals suggests that the hot spot and an adjacent non-polar region are
      spatially conserved. These results highlight for the first time structural
      elements that constitute a putative "pharmacophore" involved in the interaction
      of beta-toxins with receptor site-4 on NaChs. Furthermore, the unique structure
      of the C-terminal region most likely determines the specificity of excitatory
      toxins for insect NaChs.

PMID- 14672948
TI  - Human synaptobrevin-like 1 gene basal transcription is regulated through the
      interaction of selenocysteine tRNA gene transcription activating factor-zinc
      finger 143 factors with evolutionary conserved cis-elements.
AB  - The synaptobrevin-like 1 (SYBL1) gene is ubiquitously expressed and codes for an
      unusual member of the v-SNAREs molecules implicated in cellular exocytosis. This
      X-linked gene has the peculiarity of also being present on the Y chromosome in a
      transcriptional inactive status. Moreover, although ubiquitous, the function of
      SYBL1 is prominent in specific tissues, such as brain. As a first insight into
      the molecular mechanisms controlling SYBL1 expression, in this report we describe
      the extent and role of SYBL1 upstream regions and characterize the binding of
      trans-acting factors. In vivo foot-printing experiments identify three protected
      regions. Band shift and transient reporter gene assays indicate a strong role of
      two of these evolutionary conserved regions in regulating SYBL1 transcription.
      Because one site is the classical CAAT box, we characterized the binding to the
      other site of the mammalian homologues of the selenocysteine tRNA gene
      transcription activating factor (Staf) family, zinc-finger transcription factors,
      and their role in regulating SYBL1 expression. The results reported here clarify
      that a Staf-zinc finger family factor, together with the CAAT factor, is the
      major nuclear protein bound to the SYBL1 promoter region and is responsible for
      its regulation in HeLa cells, thus identifying the basic control of SYBL1
      transcription. In vivo binding of Staf proteins to the SYBL1 promoter is
      confirmed by chromatin immunoprecipitation assays. Our results identify a fourth
      mRNA promoter stimulated by a member of the Staf-zinc finger family, the function
      of which on mRNA polymerase II promoters is still very poorly understood.

PMID- 14672949
TI  - Proteasome mediates dopaminergic neuronal degeneration, and its inhibition causes
      alpha-synuclein inclusions.
AB  - Parkinson's disease is characterized by dopaminergic neuronal death and the
      presence of Lewy bodies. alpha-Synuclein is a major component of Lewy bodies, but
      the process of its accumulation and its relationship to dopaminergic neuronal
      death has not been resolved. Although the pathogenesis has not been clarified,
      mitochondrial complex I is suppressed, and caspase-3 is activated in the affected
      midbrain. Here we report that a combination of 1-methyl-4-phenylpyridinium ion
      (MPP(+)) or rotenone and proteasome inhibition causes the appearance of alpha
      synuclein-positive inclusion bodies. Unexpectedly, however, proteasome inhibition
      blocked MPP(+)- or rotenone-induced dopaminergic neuronal death. MPP(+) elevated
      proteasome activity, dephosphorylated mitogen-activating protein kinase (MAPK),
      and activated caspase-3. Proteasome inhibition reversed the MAPK
      dephosphorylation and blocked caspase-3 activation; the neuroprotection was
      blocked by a p42 and p44 MAPK kinase inhibitor. Thus, the proteasome plays an
      important role in both inclusion body formation and dopaminergic neuronal death
      but these processes form opposite sides on the proteasome regulation in this
      model.

PMID- 14672950
TI  - Soluble CuA domain of cyanobacterial cytochrome c oxidase.
AB  - The genomes of several cyanobacteria show the existence of gene clusters encoding
      subunits I, II, and III of aa(3)-type cytochrome c oxidase. The enzyme occurs on
      both plasma and thylakoid membranes of these oxygenic phototrophic prokaryotes.
      Here we report the expression and purification of a truncated subunit II copper A
      (Cu(A)) domain (i.e. the electron entry and donor binding site) of cytochrome c
      oxidase from the cyanobacterium Synechocystis PCC 6803 in high yield. The water
      soluble purple redox-active bimetallic center displays a relatively low standard
      reduction potential of 216 mV. Its absorption spectrum at pH 7 is similar to that
      of other soluble fragments from aa(3)-type oxidases, but the insensitivity of
      both absorbance and circular dichroism spectra to pH suggests that it is less
      exposed to the aqueous milieu compared with other Cu(A) domains. Oxidation of
      horse heart cytochrome c by the bimetallic center follows monophasic kinetics. At
      pH 7 and low ionic strength the bimolecular rate constant is (2.1 +/- 0.3) x
      10(4) m-1 s(-1), and the rates decrease upon the increase of ionic strength.
      Sequence alignment and modeling of cyanobacterial Cu(A) domains show several
      peculiarities such as: (i) a large insertion located between the second
      transmembrane region and the putative hydrophobic cytochrome c docking site, (ii)
      the lack of acidic residues shown to be important in the interaction between
      cytochrome c and Paracoccus Cu(A) domain, and (iii) an extended C terminus
      similar to Escherichia coli ubiquinol oxidase.

PMID- 14672951
TI  - Fate of RNA polymerase II stalled at a cisplatin lesion.
AB  - Elongating RNA polymerase II blocked by DNA damage in the transcribed DNA strand
      is thought to initiate the transcription-coupled repair process. The objective of
      this study is to better understand the sequence of events that occurs during
      repair from the time RNA polymerase II first encounters the lesion. This study
      establishes that an immobilized DNA template containing a unique cisplatin lesion
      can serve as an in vitro substrate for both transcription and DNA repair. RNA
      polymerase II is quantitatively stalled at the cisplatin lesion during
      transcription and can be released from the template, along with the nascent
      transcript, in an ATP-dependent manner. RNA polymerase II stalled at a lesion and
      containing a dephosphorylated repetitive carboxyl-terminal domain (CTD) appears
      to be more sensitive toward release. However, a dephosphorylated CTD can become
      readily phosphorylated in front of the lesion by CTD kinases in the presence of
      ATP. The observation that RNA polymerase II and transcript release occurs in a
      TFIIH-deficient repair extract but not in a reconstituted repair system
      demonstrates that disassembly of the elongation complex can occur independently
      of the repair process and vice versa. Indeed, the presence of RNA polymerase II
      at the lesion does not prevent dual incision from occurring. Finally, we also
      propose that the Cockayne's syndrome B protein factor, believed to be the
      mammalian transcription repair coupling factor, is neither involved in transcript
      release nor required for dual incision in the presence of lesionstalled RNA
      polymerase II in vitro. More likely, it prevents RNA polymerase from backing up
      when it encounters the lesion. The ability to transcribe and repair the same
      damaged DNA molecule fixed on beads, along with the fact that the reaction
      conditions can be freely altered, provides a powerful tool to study the fate of
      RNA polymerase II blocked on the cisplatin lesion.

PMID- 14672952
TI  - PTPH1 is a predominant protein-tyrosine phosphatase capable of interacting with
      and dephosphorylating the T cell receptor zeta subunit.
AB  - Protein-tyrosine phosphatases (PTPases) play key roles in regulating tyrosine
      phosphorylation levels in cells, yet the identity of their substrates remains
      limited. We report here on the identification of PTPases capable of
      dephosphorylating the phosphorylated immune tyrosine-based activation motifs
      present in the T cell receptor zeta subunit. To characterize these PTPases, we
      purified enzyme activities directed against the phosphorylated T cell receptor
      zeta subunit by a combination of anion and cation chromatography procedures. A
      novel ELISA-based PTPase assay was developed to rapidly screen protein fractions
      for enzyme activity following the various chromatography steps. We present data
      that SHP-1 and PTPH1 are present in highly enriched protein fractions that
      exhibit PTPase activities toward a tyrosine-phosphorylated TCR zeta substrate
      (specific activity ranging from 0.23 to 40 pmol/min/microg). We also used a
      protein-tyrosine phosphatase substrate-trapping library comprising the catalytic
      domains of 47 distinct protein-tyrosine phosphatases, representing almost all the
      tyrosine phosphatases identified in the human genome. PTPH1 was the predominant
      phosphatase capable of complexing phospho-zeta. Subsequent transfection assays
      indicated that SHP-1 and PTPH1 are the two principal PTPases capable of
      regulating the phosphorylation state of the TCR zeta ITAMs, with PTPH1 directly
      dephosphorylating zeta. This is the first reported demonstration that PTPH1 is a
      candidate PTPase capable of interacting with and dephosphorylating TCR zeta.

PMID- 14672953
TI  - Inhibitory effect of the small heterodimer partner on hepatocyte nuclear factor-4
      mediates bile acid-induced repression of the human angiotensinogen gene.
AB  - Bile acids function as transcriptional regulators for the genes important in bile
      acid synthesis and cholesterol homeostasis. In this study, we identified
      angiotensinogen (ANG), the precursor of vasoactive octapeptide angiotensin II, as
      a novel target gene of bile acids. In human ANG transgenic mice, administration
      of cholic acid resulted in the down-regulation of human ANG gene expression in
      the liver. ANG gene expression in HepG2 cells was also repressed by
      chenodeoxycholic acid. Because the expression of small heterodimer partner (SHP)
      mRNA was induced by chenodeoxycholic acid in HepG2 cells, we analyzed the effects
      of SHP on the human ANG promoter. Promoter mutation analysis demonstrated that
      SHP repressed human ANG promoter activity through the element, which has been
      previously determined as a binding site for hepatocyte nuclear factor-4 (HNF-4).
      SHP repressed human ANG promoter activity only when the HNF-4 expression vector
      was cotransfected in HeLa cells. Furthermore, we found that SHP bound to the HNF
      4 N-terminal region including the DNA-binding domain and activation function-1
      and that SHP prevented HNF-4 from binding to the human ANG promoter. These
      results suggest that bile acids negatively regulate the human ANG gene through
      the inhibitory effect of SHP on HNF-4.

PMID- 14672954
TI  - Novel physiological modulation of the Pu promoter of TOL plasmid: negative
      regulatory role of the TurA protein of Pseudomonas putida in the response to
      suboptimal growth temperatures.
AB  - From crude protein extracts of Pseudomonas putida KT2440, we identified a small
      protein, TurA, able to bind to DNA fragments bearing the entire Pu promoter
      sequence of the TOL plasmid. The knock-out inactivation of the turA gene resulted
      in enhanced transcription initiation from the Pu promoter, initially suggesting a
      negative regulatory role of TurA on Pu expression. Ectopic expression of TurA
      both in P. putida and in Escherichia coli reporter strains and transcription in
      vitro of the Pu promoter in the presence of purified TurA confirmed the TurA
      repressor role on Pu activity. turA gene inactivation did not significantly alter
      two well characterized physiological regulations of the Pu expression in routine
      conditions of cultivation, exponential silencing, and carbon-mediated repression,
      respectively. However, the growth at suboptimal temperatures resulted in a TurA
      dependent increase of Pu repression. These results strongly suggest that a
      physiological significance of the negative role of TurA on Pu activity could be
      limitation of the expression of the toluene-degrading enzymes at suboptimal
      growth temperatures. Therefore, the identification of TurA as Pu-binding protein
      revealed a novel physiological modulation of Pu promoter that is different from
      those strictly nutritional described previously.

PMID- 14672955
TI  - Stable gene silencing in human monocytic cell lines using lentiviral-delivered
      small interference RNA. Silencing of the p110alpha isoform of phosphoinositide 3
      kinase reveals differential regulation of adherence induced by 1alpha,25
      dihydroxycholecalciferol and bacterial lipopolysaccharide.
AB  - Studying mononuclear phagocyte cell biology through genetic manipulation by non
      viral transfection methods has been challenging due to the dual problems of low
      transfection efficiency and the difficulty in obtaining stable transfection. To
      overcome this problem, we developed a system for mediating RNA interference in
      monocytic cells. The p110alpha isoform of phosphoinositide 3-kinases (PI3Ks) was
      silenced using a lentiviral vector expressing short hairpin RNA (shRNA). This
      resulted in the generation of stable THP-1 and U-937 monocytic cell lines
      deficient in p110alpha. Notably, p110alpha was silenced without affecting levels
      of either the other class I(A) PI3K catalytic subunits p110beta and p110delta, or
      the p85alpha regulatory subunit. The role of p110alpha in mediating cell
      adherence was examined. Monocyte adherence induced in response to either
      lipopolysaccharide (LPS) or 1alpha,25-dihydroxycholecalciferol (D(3)) was blocked
      by the PI3K inhibitor LY294002. However, although adherence induced in response
      to D(3) was sensitive to silencing of p110alpha, LPS-induced adherence was not.
      Expression of the monocyte differentiation marker CD11b was also induced by D(3)
      in a PI3K-dependent manner and gene silencing using shRNA showed that p110alpha
      was also required for this effect. Taken together, these findings demonstrate
      that LPS and D(3) use distinct isoforms of class I(A) PI3K to induce functional
      responses and that lentiviral-mediated delivery of shRNA is a powerful approach
      to study monocyte biology.

PMID- 14672956
TI  - Functional properties of sarcoplasmic reticulum Ca(2+)-ATPase after proteolytic
      cleavage at Leu119-Lys120, close to the A-domain.
AB  - By measuring the phosphorylation levels of individual proteolytic fragments of
      SERCA1a separated by electrophoresis after their phosphorylation, we were able to
      study the catalytic properties of a p95C-p14N complex arising from SERCA1a
      cleavage by proteinase K between Leu(119) and Lys(120), in the loop linking the A
      domain with the second transmembrane segment. ATP hydrolysis by the complex was
      very strongly inhibited, although ATP-dependent phosphorylation and the
      conversion of the ADP-sensitive E1P form to E2P still occurred at appreciable
      rates. However, the rate of subsequent dephosphorylation of E2P was inhibited to
      a dramatic extent, and this was also the case for the rate of "backdoor"
      formation of E2P from E2 and P(i). E2P formation from E2 at equilibrium
      nevertheless indicated little change in the apparent affinity for P(i) or Mg(2+),
      while binding of orthovanadate was weaker. The p95C-p14N complex also had a
      slightly reduced affinity for Ca(2+) and exhibited a reduced rate for its Ca(2+)
      dependent transition from E2 to Ca(2)E1. Thus, disruption of the N-terminal link
      of the A-domain with the transmembrane region seems to shift the conformational
      equilibria of Ca(2+)-ATPase from the E1/E1P toward the E2/E2P states and to
      increase the activation energy for dephosphorylation of Ca(2+)-ATPase, reviving
      the old idea of the A-domain being a phosphatase domain as part of the
      transduction machinery.

PMID- 14672957
TI  - Peroxynitrite irreversibly inactivates the human xenobiotic-metabolizing enzyme
      arylamine N-acetyltransferase 1 (NAT1) in human breast cancer cells: a cellular
      and mechanistic study.
AB  - Arylamine N-acetyltransferases (NATs) play an important role in the
      detoxification and metabolic activation of a variety of aromatic xenobiotics,
      including numerous carcinogens. Both of the human isoforms, NAT1 and NAT2,
      display interindividual variations, and associations between NAT genotypes and
      cancer risk have been established. Contrary to NAT2, NAT1 has a ubiquitous tissue
      distribution and has been shown to be expressed in cancer cells. Given that the
      activity of NAT1 depends on a reactive cysteine that can be a target for
      oxidants, we studied whether peroxynitrite, a highly reactive nitrogen species
      involved in human carcinogenesis, could inhibit the activity of endogenous NAT1
      in MCF7 breast cancer cells. We show here that exposure of MCF7 cells to
      physiological concentrations of peroxynitrite and to a peroxynitrite generator (3
      morpholinosydnonimine N-ethylcarbamide, or SIN1) leads to the irreversible
      inactivation of NAT1 in cells. Further kinetic and mechanistic analyses using
      recombinant NAT1 showed that the enzyme is rapidly (k(inact) = 5 x 10(4) m(-1).s(
      1)) and irreversibly inactivated by peroxynitrite. This inactivation is due to
      oxidative modification of the catalytic cysteine. We conclude that the reducing
      cellular environment of MCF7 cells does not sufficiently protect NAT1 from
      peroxynitrite-dependent inactivation and that only high concentrations of reduced
      glutathione could significantly protect NAT1. Thus, cellular generation of
      peroxynitrite may contribute to carcinogenesis and tumor progression by weakening
      key cellular defense enzymes such as NAT1.

PMID- 14672958
TI  - Cardioprotective effects of exercise training on myofilament calcium activation
      in ovariectomized rats.
AB  - The risks associated with hormone replacement therapy, especially cardiac
      diseases in postmenopausal women, have prompted extensive studies for other
      preventive or therapeutic alternatives. We investigated the cardioprotective
      effects of exercise training on the changes in cardiac myofilament Ca2+
      activation in 10-wk-old ovariectomized rats. The exercise groups were subjected
      to a 9-wk running program on a motor-driven treadmill 1 wk after surgery. The
      relationship between pCa (-log molar free Ca2+ concentration) and myofibrillar
      MgATPase activity of exercise-sham myofibrils or exercise-ovariectomized
      myofibrils was the same and could not be distinguished from that of sedentary
      sham control hearts. In contrast, a significant suppression in maximum MgATPase
      activity and a leftward shift of pCa50 (half-maximally activating pCa) in the pCa
      ATPase activity relationship were detected in sedentary-ovariectomized rats.
      Exercise training also prevented the shift in myosin heavy chain (MHC) isoforms
      toward beta-MHC in ovariectomized hearts. The upregulation of beta1-adrenergic
      receptors in the left ventricular membranes of ovariectomized rat hearts, as
      measured by receptor binding and immunoblot analyses, was no longer observed in
      exercise-ovariectomized hearts. Immunoblot analyses of heat shock protein (HSP)
      72, an inducible form of HSP70, demonstrated a significant downregulation in
      ovariectomized hearts. Exercise training in ovariectomized rats completely
      reversed the expression of HSP72 to the same level as sham controls. Our results
      clearly indicate the cardioprotective effects of exercise training on changes in
      cardiac myofilament Ca2+ activation in ovariectomized rats. Alterations in
      expression of beta1-adrenergic receptors and HSP72 may, in part, play a
      mechanistic role in the cardioprotective effects.

PMID- 14672959
TI  - Dust mite-induced asthma in cynomolgus monkeys.
AB  - Animal models exhibiting high homology with humans at the genetic and
      pathophysiological levels will facilitate identification and validation of gene
      targets underlying asthma. In the present study, a nonhuman primate model of
      allergic asthma was developed by sensitizing cynomolgus monkeys to dust mite
      antigen. Sensitization elevated allergen-specific serum IgE and IgG levels, and
      peripheral blood mononuclear cells isolated from sensitized animals released IL
      4, IL-5, and IL-10, but not IFN-gamma. Aerosolized allergen decreased dynamic
      compliance and induced airway inflammation and hyperresponsiveness to aerosolized
      histamine. Albuterol and dexamethasone inhibited the airway constriction and
      allergen-induced inflammation, respectively. Airway wall remodeling that included
      goblet cell hyperplasia, basement membrane thickening, and smooth muscle
      hypertrophy was particularly evident in neonatally sensitized animals. In
      contrast to animals sensitized as adults, neonatally sensitized animals exhibited
      increased sensitivity to adenosine and larger allergen-induced changes in airway
      resistance and dynamic compliance. These results demonstrate that sensitization
      of cynomolgus monkeys with dust mite induces asthmalike symptoms, some of which
      may be dependent on age at the time of sensitization.

PMID- 14672960
TI  - NaHCO(3) does not affect arterial O(2) tension but attenuates desaturation of
      hemoglobin in maximally exercising Thoroughbreds.
AB  - The objective of the present study was to examine the effects of preexercise
      NaHCO(3) administration to induce metabolic alkalosis on the arterial oxygenation
      in racehorses performing maximal exercise. Two sets of experiments, intravenous
      physiological saline and NaHCO(3) (250 mg/kg i.v.), were carried out on 13
      healthy, sound Thoroughbred horses in random order, 7 days apart. Blood-gas
      variables were examined at rest and during incremental exercise, leading to 120 s
      of galloping at 14 m/s on a 3.5% uphill grade, which elicited maximal heart rate
      and induced pulmonary hemorrhage in all horses in both treatments. NaHCO(3)
      administration caused alkalosis and hemodilution in standing horses, but arterial
      O(2) tension and hemoglobin-O(2) saturation were unaffected. Thus NaHCO(3)
      administration caused a reduction in arterial O(2) content at rest, although the
      arterial-to-mixed venous blood O(2) content gradient was unaffected. During
      maximal exercise in both treatments, arterial hypoxemia, desaturation,
      hypercapnia, acidosis, hyperthermia, and hemoconcentration developed. Although
      the extent of exercise-induced arterial hypoxemia was similar, there was an
      attenuation of the desaturation of arterial hemoglobin in the NaHCO(3)-treated
      horses, which had higher arterial pH. Despite these observations, the arterial
      blood O(2) content of exercising horses was less in the NaHCO(3) experiments
      because of the hemodilution, and an attenuation of the exercise-induced expansion
      of the arterial-to-mixed venous blood O(2) content gradient was observed. It was
      concluded that preexercise NaHCO(3) administration does not affect the
      development and/or severity of arterial hypoxemia in Thoroughbreds performing
      short-term, high-intensity exercise.

PMID- 14672961
TI  - Alterations in PKC signaling underlie enhanced myogenic tone in exercise-trained
      porcine coronary resistance arteries.
AB  - The intracellular mechanisms underlying enhanced myogenic contraction (MC) in
      coronary resistance arteries (CRAs) from exercise-trained (EX) pigs have not been
      established. The purpose of this study was to test the hypothesis that exercise
      induced alterations in protein kinase C (PKC) signaling underlie enhanced MC.
      Furthermore, we sought to determine whether modulation of intracellular Ca(2+)
      signaling by PKC underlies enhanced MC in EX animals. Male Yucatan miniature
      swine were treadmill trained (n = 7) at approximately 75% of maximal O(2) uptake
      for 16 wk (6 miles/h, 60 min) or remained sedentary (SED, n = 6). Diameter
      measurements in response to intraluminal pressure (60, 75, and 90 cmH(2)O) or 60
      mM KCl were determined in single, cannulated CRAs ( approximately 100 microm ID)
      with and without the PKC inhibitor chelerythrine (CE, 1 microM). Confocal imaging
      of Ca(2+) signaling [myogenic Ca(2+) (Ca(m))] was also performed in CRAs of
      similar internal diameter after abluminal loading of the Ca(2+) indicator dye
      fluo 4 (1 microM, 37 degrees C, 30 min). We observed significantly greater MC in
      CRAs isolated from EX than from SED animals at 90 cmH(2)O, as well as greater
      reductions in MC after CE at all pressures studied. At intraluminal pressures of
      75 and 90 cmH(2)O, CE produced greater decreases in Ca(m) in CRAs from EX than
      from SED animals (64% vs. 25%, P < 0.05). Inhibition of KCl constriction and
      Ca(m) by CE was also greater in EX animals (P < 0.05). Western blotting revealed
      significant increases in Ca(2+)-dependent PKC-alpha ( approximately 50%) but not
      Ca(2+)-independent PKC-epsilon levels in CRAs isolated from EX animals (P <
      0.05). We also observed significant group differences in phosphorylated PKC-alpha
      levels. Finally, voltage-gated Ca(2+) current (VGCC) was effectively blocked by
      CE, bisindolylmaleimide, and staurosporine in isolated smooth muscle cells from
      CRAs, providing evidence for a mechanistic link between VGCCs and PKC in our
      experimental paradigm. These results suggest that enhanced MC in CRAs from EX
      animals involves PKC-dependent modulation of intracellular Ca(2+), including
      regulation of VGCCs.

PMID- 14672962
TI  - Influence of carbohydrate ingestion on immune changes after 2 h of intensive
      resistance training.
AB  - Thirty strength-trained subjects were randomized to carbohydrate (CHO) or placebo
      (Pla) groups and lifted weights for 2 h (10 exercises, 4 sets each, 10
      repetitions, with 2- to 3-min rest intervals). Subjects received 10 ml x kg(-1) x
      h(-1) CHO (6%) or Pla beverages during the weight training bout. Blood, saliva,
      and vastus lateralis muscle biopsy samples were collected before and after
      exercise. Blood cell counts were determined, and plasma was analyzed for IL-6, IL
      10, IL-1 receptor antagonist (IL-1ra), IL-8, and cortisol. Muscle was analyzed
      for glycogen content and relative gene expression of 13 cytokines (IL-1alpha, IL
      1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-gamma,
      TNF-alpha) by use of real-time quantitative RT-PCR. Significant but modest
      increases were measured for plasma IL-6, IL-10, IL-1ra, and IL-8, but the pattern
      of increase did not differ between CHO and Pla groups. The rate of decrease in
      muscle glycogen content did not differ between CHO and Pla (P = 0.463). Muscle
      cytokine mRNA was detected preexercise for IL-1beta, IL-6, IL-15, IL-8, and TNF
      alpha, and of these, IL-1beta, IL-6, IL-8, and TNF-alpha were significantly
      increased after the 2-h weight training bout. The increase in mRNA (fold
      difference from preexercise) did not differ between CHO and Pla groups. In
      summary, CHO vs. Pla ingestion did not alter modest increases measured for plasma
      IL-6, IL-10, IL-1ra, and IL-8, and muscle gene expression for IL-1beta, IL-6, IL
      8, and TNF-alpha in strength-trained subjects lifting weights intensively for 2
      h.

PMID- 14672963
TI  - Low-threshold motor unit membrane properties vary with contraction intensity
      during sustained activation with surface EMG visual feedback.
AB  - Single-motor unit (MU) activities were detected from the abductor pollicis and
      abductor digiti minimi muscles providing the subjects with visual feedback of
      multichannel surface electromyogram (EMG) signals. The subjects could modulate
      the force to observe on the surface recordings a single dominant MU and modulate
      its firing rate for contractions of 300 s with a noninvasive EMG feedback. The
      firing rate was maintained at approximately 8 pulses per second [low-frequency
      (LF) contraction] and at approximately 12 pulses per second [high-frequency (HF)
      contraction]. Single-MU conduction velocity (CV) decreased slightly but
      significantly over time, and it was possible to identify a significantly larger
      rate of decrease of CV during the HF with respect to the LF contractions. CV
      initial value significantly increased with the average firing rate, and CV values
      were significantly correlated to the instantaneous firing rate (R ranging from
      0.21 to 0.39). Both additional MU recruitment and substitution were observed
      during the contractions. The study provides evidence that 1). it is possible to
      follow the same MU in a hand muscle at two different intensities (HF and LF) for
      300-s durations by using visual feedback of surface EMG, 2). low-threshold single
      MU CV changes over time since the beginning of the contraction, and 3). it is
      possible to distinguish between CV changes of the same MU at slightly different
      firing rates. The technique provides a practical method for the noninvasive
      assessment of both control and membrane properties of single MUs.

PMID- 14672964
TI  - Effects of ventilation on the collection of exhaled breath in humans.
AB  - A computerized system has been developed to monitor tidal volume, respiration
      rate, mouth pressure, and carbon dioxide during breath collection. This system
      was used to investigate variability in the production of breath biomarkers over
      an 8-h period. Hyperventilation occurred when breath was collected from
      spontaneously breathing study subjects (n = 8). Therefore, breath samples were
      collected from study subjects whose breathing were paced at a respiration rate of
      10 breaths/min and whose tidal volumes were gauged according to body mass. In
      this "paced breathing" group (n = 16), end-tidal concentrations of isoprene and
      ethane correlated with end-tidal carbon dioxide levels [Spearman's rank
      correlation test (r(s)) = 0.64, P = 0.008 and r(s) = 0.50, P = 0.05,
      respectively]. Ethane also correlated with heart rate (r(s) = 0.52, P < 0.05).
      There was an inverse correlation between transcutaneous pulse oximetry and
      exhaled carbon monoxide (r(s) = -0.64, P = 0.008). Significant differences were
      identified between men (n = 8) and women (n = 8) in the concentrations of carbon
      monoxide (4 parts per million in men vs. 3 parts per million in women; P = 0.01)
      and volatile sulfur-containing compounds (134 parts per billion in men vs. 95
      parts per billion in women; P = 0.016). There was a peak in ethanol concentration
      directly after food consumption and a significant decrease in ethanol
      concentration 2 h later (P = 0.01; n = 16). Sulfur-containing molecules increased
      linearly throughout the study period (beta = 7.4, P < 0.003). Ventilation
      patterns strongly influence quantification of volatile analytes in exhaled breath
      and thus, accordingly, the breathing pattern should be controlled to ensure
      representative analyses.

PMID- 14672965
TI  - Effects on breathing in awake and sleeping goats of focal acidosis in the
      medullary raphe.
AB  - Our aim was to determine the effects of focal acidification in the raphe obscurus
      (RO) and raphe pallidus (RP) on ventilation and other physiological variables in
      both the awake and sleep states in adult goats. Through chronically implanted
      microtubules, 1) a focal acidosis was created by microdialysis of mock
      cerebrospinal fluid (mCSF), equilibrated with various levels of CO2, and 2)
      medullary extracellular fluid (ECF) pH was measured by using a custom-made pH
      electrode. Focal acidosis in the RO or RP, by dialyzing either 25 or 80% CO2
      (mCSF pH approximately 6.8 or 6.3), increased (P < 0.05) inspiratory flow by 8
      and 12%, respectively, while the animals were awake during the day, but not at
      night while they were awake or in non-rapid eye movement sleep. While the animals
      were awake during the day, there were also increases in heart rate and blood
      pressure (P < 0.05) but no significant change in metabolic rate or arterial Pco2.
      Dialysis with mCSF equilibrated with 25 or 80% CO2 reduced ECF pH by the same
      amount (25%) or three times more (80%) than when inspired CO2 was increased to
      7%. During CO2 inhalation, the reduction in ECF pH was only 50% of the reduction
      in arterial pH. Finally, dialysis in vivo only decreased ECF pH by 19.1% of the
      change during dialysis in an in vitro system. We conclude that 1) the
      physiological responses to focal acidosis in the RO and RP are consistent with
      the existence of chemoreceptors in these nuclei, and 2) local pH buffering
      mechanisms act to minimize changes in brain pH during systemic induced acidosis
      and microdialysis focal acidosis and that these mechanisms could be as or more
      important to pH regulation than the small changes in inspiratory flow during a
      focal acidosis.

PMID- 14672966
TI  - No alpha-adrenoreceptor-induced C-fiber activation in healthy human skin.
AB  - In healthy volunteers, flare responses induced by norepinephrine (NE)
      iontophoresis have been observed. However, as NE iontophoresis is a combined
      electrical and chemical stimulus axon, reflexes cannot be directly linked to
      pharmocological activity of NE. Different concentrations of NE, clonidine (CL),
      and phenylephrine (PE) (NE: 10(-10)-10(-3) M; CL and PE: 10(-8)-10(-3) M) were
      applied via intradermal microdialysis fibers into the skin of healthy volunteers.
      Simultaneously, skin blood flow was visualized by laser-Doppler imaging scans and
      quantified in a vasoconstriction skin area directly above the membranes to
      control drug effects and in expected axon reflex vasodilation areas that were
      0.75 cm apart. NE, PE, and CL caused dose-dependent vasoconstriction. However,
      neither in the presumed axon reflex areas (quantitative analysis) nor on laser
      Doppler imaging pictures (qualitative analysis) were any vasodilation observed.
      Even at concentrations causing maximum vasoconstriction (10(-3) M for any drug),
      no vasodilation was induced. Our results indicate that, in healthy human skin,
      exogenously supplied alpha-adrenoreceptor agonists alone do not activate
      nociceptors sufficiently to induce axon reflex flare.

PMID- 14672967
TI  - Intermittent normobaric hypoxia does not alter performance or erythropoietic
      markers in highly trained distance runners.
AB  - This study was designed to test the hypothesis that intermittent normobaric
      hypoxia at rest is a sufficient stimulus to elicit changes in physiological
      measures associated with improved performance in highly trained distance runners.
      Fourteen national-class distance runners completed a 4-wk regimen (5:5-min
      hypoxia-to-normoxia ratio for 70 min, 5 times/wk) of intermittent normobaric
      hypoxia (Hyp) or placebo control (Norm) at rest. The experimental group was
      exposed to a graded decline in fraction of inspired O2: 0.12 (week 1), 0.11 (week
      2), and 0.10 (weeks 3 and 4). The placebo control group was exposed to the same
      temporal regimen but breathed fraction of inspired O2 of 0.209 for the entire 4
      wk. Subjects were matched for training history, gender, and baseline measures of
      maximal O2 uptake and 3,000-m time-trial performance in a randomized, balanced,
      double-blind design. These parameters, along with submaximal treadmill
      performance (economy, heart rate, lactate, and ventilation), were measured in
      duplicate before, as well as 1 and 3 wk after, the intervention. Hematologic
      indexes, including serum concentrations of erythropoietin and soluble transferrin
      receptor and reticulocyte parameters (flow cytometry), were measured twice before
      the intervention, on days 1, 5, 10, and 19 of the intervention, and 10 and 25
      days after the intervention. There were no significant differences in maximal O2
      uptake, 3,000-m time-trial performance, erythropoietin, soluble transferrin
      receptor, or reticulocyte parameters between groups at any time. Four weeks of a
      5:5-min normobaric hypoxia exposure at rest for 70 min, 5 days/wk, is not a
      sufficient stimulus to elicit improved performance or change the normal level of
      erythropoiesis in highly trained runners.

PMID- 14672968
TI  - Loss of exercise-induced cardioprotection after cessation of exercise.
AB  - Endurance exercise provides cardioprotection against ischemia-reperfusion (I/R)
      injury. Exercise-induced cardioprotection is associated with increases in
      cytoprotective proteins, including heat shock protein 72 (HSP72) and increases in
      antioxidant enzyme activity. On the basis of the reported half-life of these
      putative cardioprotective proteins, we hypothesized that exercise-induced
      cardioprotection against I/R injury would be lost within days after cessation of
      exercise. To test this, male rats (4 mo) were randomly assigned to one of five
      experimental groups: 1). sedentary control, 2). exercise followed by 1 day of
      rest, 3). exercise followed by 3 days of rest, 4). exercise followed by 9 days of
      rest, and 5). exercise followed by 18 days of rest. Exercise-induced increases (P
      < 0.05) in left ventricular catalase activity and HSP72 were evident at 1 and 3
      days postexercise. However, at 9 days postexercise, myocardial HSP72 and catalase
      levels declined to sedentary control values. To evaluate cardioprotection during
      recovery from I/R, hearts were isolated, placed in working heart mode, and
      subjected to 20.5 min of global ischemia followed by 30 min of reperfusion.
      Compared with sedentary controls, exercised animals sustained less I/R injury as
      evidenced by maintenance of a higher (P < 0.05) percentage of preischemia cardiac
      work during reperfusion at 1, 3, and 9 days postexercise. The exercise-induced
      cardioprotection vanished by 18 days after exercise cessation. On the basis of
      the time course of the loss of cardioprotection and the return of HSP72 and
      catalase to preexercise levels, we conclude that HSP72 and catalase are not
      essential for exercise-induced protection during myocardial stunning. Therefore,
      other cytoprotective molecules are responsible for providing protection during
      I/R.

PMID- 14672969
TI  - Effects of voluntary exercise and genetic selection for high activity levels on
      HSP72 expression in house mice.
AB  - We studied expression of heat shock protein 72 (HSP72) in female mice from four
      replicate lines that had been selectively bred for high voluntary wheel running
      (S) and from four random-bred control lines (C). Mice from generation 23 were
      sampled after 6 days of wheel access, and those from generation 14 were sampled
      after 8 wk of access to wheels either free to rotate or locked. Mice from S lines
      ran approximately 2.6 times as many revolutions per day as did those from C
      lines. Western blotting of tissues from generation 23 mice indicated that S mice
      had elevated HSP72 expression in triceps surae muscle, but levels in spleen,
      kidney, heart, and lung were similar in S and C mice. HSP72 expression in triceps
      surae from generation 14 mice was measured by ELISA and analyzed with a two-way
      analysis of covariance. The interaction between wheel type and line type (S vs.
      C) was statistically significant, and subsequent analyses indicated that S mice
      had significantly elevated HSP72 expression only when housed with free wheels.
      Mice with the previously described mini-muscle phenotype (Houle-Leroy P, Guderley
      H, Swallow JG, and Garland T Jr. Am J Physiol Regul Integr Comp Physiol 284: R433
      R443, 2003) occurred in both generations and had elevated HSP72 expression in
      triceps surae. For the generation 23 sample, wheel running as a covariate had a
      significant negative association with HSP72 expression, and the effect of line
      type was still statistically significant. Therefore, the increased HSP72
      expression of S mice is not a simple proximate effect of their increased wheel
      running.

PMID- 14672970
TI  - Exercise training-induced adaptations of immune response are mediated by beta
      adrenergic receptors in aged but not young mice.
AB  - Beta-adrenergic blockade was used to determine whether the exercise training
      induced adaptations of immune response to viral infection were mediated by
      catecholamines in young and old mice. Young (2 mo) and older (16 mo) male BALB/c
      mice were randomly assigned to an exercise or control group, and half of the mice
      in each group received the beta-adrenergic receptor antagonist nadolol. After 8
      wk of moderate exercise training, mice were challenged with herpes simplex virus
      (HSV) 24 h postexercise. The results showed that exercise treatment increased
      anti-HSV IgM antibody, enhanced IL-10, and altered the kinetics of IFN-gamma and
      IL-2 production in young and old mice. Unique to older mice, exercise decreased
      mitogen-induced proliferation, increased splenocytes, and tended to decrease
      memory cells (CD44(hi+)). In contrast, exercise increased mitogen-induced
      proliferation but decreased the number of splenic lymphocyte and CD4+ cells in
      young mice. beta-Adrenergic blockade blunted the exercise-induced changes in anti
      HSV IgM, IL-2, IFNgamma, and mitogen-induced proliferation in old but not young
      mice. The findings suggest that some of the immunomodulatory effects of chronic
      exercise are mediated via beta-adrenergic receptors and that the role of beta
      adrenergic receptors is age dependent.

PMID- 14672971
TI  - Effects of hypergravity on the distributions of lung ventilation and perfusion in
      sitting humans assessed with a simple two-step maneuver.
AB  - Increased gravity impairs pulmonary distributions of ventilation and perfusion.
      We sought to develop a method for rapid, simultaneous, and noninvasive
      assessments of ventilation and perfusion distributions during a short-duration
      hypergravity exposure. Nine sitting subjects were exposed to one, two, and three
      times normal gravity (1, 2, and 3 G) in the head-to-feet direction and performed
      a rebreathing and a single-breath washout maneuver with a gas mixture containing
      C(2)H(2), O(2), and Ar. Expirograms were analyzed for cardiogenic oscillations
      (COS) and for phase IV amplitude to analyze inhomogeneities in ventilation (Ar)
      and perfusion [CO(2)-to-Ar ratio (CO(2)/Ar)] distribution, respectively. COS were
      normalized for changes in stroke volume. COS for Ar increased from 1-G control to
      128 +/- 6% (mean +/- SE) at 2 G (P = 0.02 for 1 vs. 2 G) and 165 +/- 13% at 3 G
      (P = 0.002 for 2 vs. 3 G). Corresponding values for CO(2)/Ar were 135 +/- 12% (P
      = 0.04) and 146 +/- 13%. Phase IV amplitude for Ar increased to 193 +/- 39% (P =
      0.008) at 2 G and 229 +/- 51% at 3 G compared with 1 G. Corresponding values for
      CO(2)/Ar were 188 +/- 29% (P = 0.02) and 219 +/- 18%. We conclude that not only
      large-scale ventilation and perfusion inhomogeneities, as reflected by phase IV
      amplitude, but also smaller-scale inhomogeneities, as reflected by the ratio of
      COS to stroke volume, increase with hypergravity. Except for small-scale
      ventilation distribution, most of the impairments observed at 3 G had been
      attained at 2 G. For some of the parameters and gravity levels, previous
      comparable data support the present simplified method.

PMID- 14672972
TI  - Optimal hemoglobin concentration and high altitude: a theoretical approach for
      Andean men at rest.
AB  - The beneficial role of erythrocytosis for O2 transport has been questioned by
      evidence from bloodletting and hemodilution research as well as by studies
      suggesting the existence of an "optimal" hematocrit (Hct) or hemoglobin
      concentration ([Hb]) value. To assess to what extent erythrocytosis is beneficial
      in Andean men at high altitude, we examined and discussed optimal [Hb] using a
      mathematical approach by modeling the mixed (mean) venous Po2 (Pv(O2)) and
      arterial O2 content, considering for both the relation between [Hb] and arterial
      Po2. Relations of [Hb] to other physiological variables such as cardiac output
      and convective arterial O2 transport were also discussed, revealing the
      importance of Pv(O2) in this model. Our theoretical analysis suggests that
      increasing [Hb] allows increase and maintenance of Pv(O2) with only moderate
      declines in arterial Po2 as a consequence of moderate increases in altitude,
      reaching its maximum at the optimal [Hb] of 14.7 g/dl. Our analysis also shows
      that [Hb] corresponding to high arterial O2 content and O2 transport values is
      apparently not quite advantageous for improvement of oxygenation. Furthermore,
      chronic mountain sickness is discussed as an insightful example of the effects of
      excessive erythrocytosis at high altitude.

PMID- 14672973
TI  - Dihydropyridine and ryanodine receptor binding after eccentric contractions in
      mouse skeletal muscle.
AB  - The purpose of this study was to determine whether there are alterations in the
      dihydropyridine and/or ryanodine receptors that might explain the excitation
      contraction uncoupling associated with eccentric contraction-induced skeletal
      muscle injury. The left anterior crural muscles (i.e., tibialis anterior,
      extensor digitorum longus, and extensor hallucis longus) of mice were injured in
      vivo by 150 eccentric contractions. Peak isometric tetanic torque of the anterior
      crural muscles was reduced approximately 45% immediately and 3 days after the
      eccentric contractions. Partial restoration of peak isometric tetanic and
      subtetanic forces of injured extensor digitorum longus muscles by 10 mM caffeine
      indicated the presence of excitation-contraction uncoupling. Scatchard analysis
      of [3H]ryanodine binding indicated that the number of ryanodine receptor binding
      sites was not altered immediately postinjury but decreased 16% 3 days later.
      Dihydropyridine receptor binding sites increased approximately 20% immediately
      after and were elevated to the same extent 3 days after the injury protocol.
      Muscle injury did not alter the sensitivity of either receptor. These data
      suggest that a loss or altered sensitivity of the dihydropyridine and ryanodine
      receptors does not contribute to the excitation-contraction uncoupling
      immediately after contraction-induced muscle injury. We also concluded that the
      loss in ryanodine receptors 3 days after injury is not the primary cause of
      excitation-contraction uncoupling at that time.

PMID- 14672974
TI  - Multiple variable first exons: a mechanism for cell- and tissue-specific gene
      regulation.
AB  - A large family of neural protocadherin (Pcdh) proteins is encoded by three
      closely linked mammalian gene clusters (alpha, beta, and gamma). Pcdh alpha and
      gamma clusters have a striking genomic organization. Specifically, each
      "variable" exon is spliced to a common set of downstream "constant" exons within
      each cluster. Recent studies demonstrated that the cell-specific expression of
      each Pcdh gene is determined bya combination of variable-exon promoter activation
      and cis-splicing of the corresponding variable exon to the first constant exon.
      To determine whether there are other similarly organized gene clusters in
      mammalian genomes, we performed a genome-wide search and identified a large
      number of mammalian genes containing multiple variable first exons. Here we
      describe several clusters that contain about a dozen variable exons arrayed in
      tandem, including UDP glucuronosyltransferase (UGT1), plectin, neuronal nitric
      oxide synthase (NOS1), and glucocorticoid receptor (GR) genes. In all these
      cases, multiple variable first exons are each spliced to a common set of
      downstream constant exons to generate diverse functional mRNAs. As an example, we
      analyzed the tissue-specific expression profile of the mouse UGT1 repertoire and
      found that multiple isoforms are expressed in a tissue-specific manner.
      Therefore, this variable and constant genomic organization provides a genetic
      mechanism for directing distinct cell- and tissue-specific patterns of gene
      expression.

PMID- 14672975
TI  - Mutational and selective pressures on codon and amino acid usage in Buchnera,
      endosymbiotic bacteria of aphids.
AB  - We have explored compositional variation at synonymous (codon usage) and
      nonsynonymous (amino acid usage) positions in three complete genomes of Buchnera,
      endosymbiotic bacteria of aphids, and also in their orthologs in Escherichia
      coli, a close free-living relative. We sought to discriminate genes of variable
      expression levels in order to weigh the relative contributions of mutational bias
      and selection in the genomic changes following symbiosis. We identified clear
      strand asymmetries, distribution biases (putative high-expression genes were
      found more often on the leading strand), and a residual slight codon bias within
      each strand. Amino acid usage was strongly biased in putative high-expression
      genes, characterized by avoidance of aromatic amino acids, but above all by
      greater conservation and resistance to AT enrichment. Despite the almost complete
      loss of codon bias and heavy mutational pressure, selective forces are still
      strong at nonsynonymous sites of a fraction of the genome. However, Buchnera from
      Baizongia pistaciae appears to have suffered a stronger symbiotic syndrome than
      the two other species.

PMID- 14672976
TI  - Fluorescent detection and isolation of DNA variants using stabilized RecA-coated
      oligonucleotides.
AB  - Several genome resequencing strategies have been developed to detect genetic
      variation in populations and correlate diversity with phenotypic consequences.
      Commonly used methods of detecting single nucleotide polymorphisms (SNPs) use PCR
      amplification and indirect analysis, which can create template biases and enable
      user contamination. Here we present a novel assay to detect and isolate DNA
      variants using stabile nanostructures formed directly on duplex DNA. The assay
      incorporates the well-established RecA-catalyzed strand invasion process with a
      novel stabilizing hybridization step. First, short RecA-coated oligonucleotide
      filaments invade duplex DNA to form a synaptic intermediate or "D-loop."
      Sequentially, chemically modified oligonucleotide probes anneal to the displaced
      DNA strand of the complex to form a stable "double D-loop." These joint molecules
      resist dissociation when both oligonucleotides are completely complementary to
      the target duplex; however, if the probes are mismatched, the complex is
      inherently instable and rapidly dissociates. SNPs are identified by detecting the
      fluorophore assimilated into stable complexes produced by homologous probes
      compared to unstable differentially labeled mismatched probes. Furthermore, this
      strategy can be used to isolate specific allelic variants by affinity
      purification from complex populations. Stabilized double D-Loop intermediates
      accordingly offer the promise of haplotyping and pharmacogenomic analysis
      directly in double-stranded DNA samples.

PMID- 14672977
TI  - CONREAL: conserved regulatory elements anchored alignment algorithm for
      identification of transcription factor binding sites by phylogenetic
      footprinting.
AB  - Prediction of transcription-factor target sites in promoters remains difficult
      due to the short length and degeneracy of the target sequences. Although the use
      of orthologous sequences and phylogenetic footprinting approaches may help in the
      recognition of conserved and potentially functional sequences, correct alignment
      of the short transcription-factor binding sites can be problematic for
      established algorithms, especially when aligning more divergent species. Here, we
      report a novel phylogenetic footprinting approach, CONREAL, that uses
      biologically relevant information, that is, potential transcription-factor
      binding sites as represented by positional weight matrices, to establish anchors
      between orthologous sequences and to guide promoter sequence alignment.
      Comparison of the performance of CONREAL with the global alignment programs LAGAN
      and AVID using a reference data set, shows that CONREAL performs equally well for
      closely related species like rodents and human, and has a clear added value for
      aligning promoter elements of more divergent species like human and fish, as it
      identifies conserved transcription-factor binding sites that are not found by
      other methods. CONREAL is accessible via a Web interface at
      http://conreal.niob.knaw.nl/.

PMID- 14672978
TI  - Whole-genome discovery of transcription factor binding sites by network-level
      conservation.
AB  - Comprehensive identification of DNA cis-regulatory elements is crucial for a
      predictive understanding of transcriptional network dynamics. Strong evidence
      suggests that these DNA sequence motifs are highly conserved between related
      species, reflecting strong selection on the network of regulatory interactions
      that underlie common cellular behavior. Here, we exploit a systems-level aspect
      of this conservation-the network-level topology of these interactions-to map
      transcription factor (TF) binding sites on a genomic scale. Using network-level
      conservation as a constraint, our algorithm finds 71% of known TF binding sites
      in the yeast Saccharomyces cerevisiae, using only 12% of the sequence of a
      phylogenetic neighbor. Most of the novel predicted motifs show strong features of
      known TF binding sites, such as functional category and/or expression profile
      coherence of their corresponding genes. Network-level conservation should provide
      a powerful constraint for the systematic mapping of TF binding sites in the
      larger genomes of higher eukaryotes.

PMID- 14672979
TI  - Recombination has little effect on the rate of sequence divergence in
      pseudoautosomal boundary 1 among humans and great apes.
AB  - Recent studies indicated that recombination is strongly mutagenic. In particular,
      data from the mouse pseudoautosomal boundary (PAB) suggested that locally
      intensive recombination increased the nucleotide substitution rate by more than
      100-fold and greatly increased the GC content. Here we study the rates of
      nucleotide substitution in eight introns of the human and great ape XG gene,
      which spans the boundary between the pseudoautosomal region 1 (PAR1) and the X
      specific region. Contrary to what is expected under the above hypothesis, our
      sequence data from humans and great apes reveal that the PAR1 introns of XG have
      actually evolved slightly slower than X-specific introns. Only when a New World
      monkey was compared with hominoids were the rates slightly increased in the PAR1
      introns. In terms of base composition, although the intergenic regions of the
      human PAR1 show a significant increase of G and C nucleotides, the base
      composition of the surveyed PAR1 introns is similar to that of the X-specific
      introns. Direct and indirect evidence indicates that the recombination rate is,
      indeed, much higher in PAR1 introns than in X-specific introns, and that the
      present PAB has persisted since the common ancestor of hominoids. Therefore, the
      mutagenic effect of recombination is far weaker than previously proposed, at
      least in hominoid PABs.

PMID- 14672980
TI  - 1-Mb resolution array-based comparative genomic hybridization using a BAC clone
      set optimized for cancer gene analysis.
AB  - Array-based comparative genomic hybridization (aCGH) is a recently developed tool
      for genome-wide determination of DNA copy number alterations. This technology has
      tremendous potential for disease-gene discovery in cancer and developmental
      disorders as well as numerous other applications. However, widespread utilization
      of a CGH has been limited by the lack of well characterized, high-resolution
      clone sets optimized for consistent performance in aCGH assays and specifically
      designed analytic software. We have assembled a set of approximately 4100
      publicly available human bacterial artificial chromosome (BAC) clones evenly
      spaced at approximately 1-Mb resolution across the genome, which includes direct
      coverage of approximately 400 known cancer genes. This aCGH-optimized clone set
      was compiled from five existing sets, experimentally refined, and supplemented
      for higher resolution and enhancing mapping capabilities. This clone set is
      associated with a public online resource containing detailed clone mapping data,
      protocols for the construction and use of arrays, and a suite of analytical
      software tools designed specifically for aCGH analysis. These resources should
      greatly facilitate the use of aCGH in gene discovery.

PMID- 14672981
TI  - Dynamic mechanical properties of body-wall dermis in various mechanical states
      and their implications for the behavior of sea cucumbers.
AB  - The dermis of the sea cucumber body wall is a typical catch connective tissue
      that rapidly changes its mechanical properties in response to various stimuli.
      Dynamic mechanical properties were measured in stiff, standard, and soft states
      of the sea cucumber Actinopyga mauritiana. Sinusoidal deformations were applied,
      either at a constant frequency of 0.1 Hz with varying maximum strain of 2%-20% or
      at a fixed maximum strain of 1.8% with varying frequency of 0.0005-50 Hz. The
      dermis showed viscoelasticity with both strain and strain-rate dependence. The
      dermis in the standard state showed a J-shaped stress-strain curve with a
      stiffness of 1 MPa and a dissipation ratio of 60%; the curve of the stiff dermis
      was linear with high stiffness (3 MPa) and a low dissipation ratio (30%). Soft
      dermis showed a J-shaped curve with low stiffness (0.3 MPa) and a high
      dissipation ratio (80%). The strain-induced softening was observed in the soft
      state. Stiff samples had a higher storage modulus and a lower tangent delta than
      soft ones, implying a larger contribution of the elastic component in the stiff
      state. A simple molecular model was proposed that accounted for the mechanical
      behavior of the dermis. The model suggested that stiffening stimulation increased
      inter-molecular bonds, whereas softening stimulation affected intra-molecular
      bonds. The adaptive significance of each mechanical state in the behavior of sea
      cucumbers is discussed.

PMID- 14672982
TI  - Heat-shock protein 70 (Hsp70) as a biochemical stress indicator: an experimental
      field test in two congeneric intertidal gastropods (genus: Tegula).
AB  - Although previous studies have demonstrated that heat-shock protein 70 (Hsp70)
      can be induced by environmental stress, little is known about natural variation
      in this response over short time scales. We examined how Hsp70 levels varied over
      days to weeks in two intertidal snail species of the genus Tegula: Sampling was
      conducted both under naturally changing environmental conditions and in different
      vertical zones on a rocky shore. The subtidal to low-intertidal T. brunnea was
      transplanted into shaded and unshaded mid-intertidal cages to assess temporal
      variation in Hsps under conditions of increased stress. For comparison, the low
      to mid-intertidal T. funebralis was transplanted into mid-intertidal cages,
      within this species' natural zone of occurrence. Snails were sampled every 3 to 4
      days for one month, and endogenous levels of two Hsp70-kDa family members (Hsp72
      and Hsp74) were quantified using solid-phase immunochemistry. Following periods
      of midday low tides, levels of Hsps increased greatly in transplanted T. brunnea
      but not in T. funebralis. Levels of Hsps increased less in T. brunnea
      transplanted to shaded cages than to unshaded cages, suggesting that prolonged
      emersion and reduction in feeding time per se are factors that are only mildly
      stressful. Upregulated levels of Hsps returned to base levels within days. In
      unmanipulated snails collected from their natural zones, Hsp levels showed little
      change with thermal variation, indicating that these species did not experience
      thermally stressful conditions during this study. However, under common
      conditions in the mid-intertidal zone, Hsp70 levels reflected the different
      thermal sensitivities of the physiological systems of these two species.

PMID- 14672983
TI  - Reproduction and larval morphology of broadcasting and viviparous species in the
      Cryptasterina species complex.
AB  - The Cryptasterina group of asterinid sea stars in Australasia comprises cryptic
      species with derived life histories. C. pentagona and C. hystera have planktonic
      and intragonadal larvae, respectively. C. pentagona has the gonochoric, free
      spawning mode of reproduction with a planktonic lecithotrophic brachiolaria
      larva. C. hystera is hermaphroditic with an intragonadal lecithotrophic
      brachiolaria, and the juveniles emerge through the gonopore. Both species have
      large lipid-rich buoyant eggs and well-developed brachiolariae. Early juveniles
      are sustained by maternal nutrients for several weeks while the digestive tract
      develops. C. hystera was reared in vitro through metamorphosis. Its brachiolariae
      exhibited the benthic exploration and settlement behavior typical of planktonic
      larvae, and they attached to the substratum with their brachiolar complex. These
      behaviors are unlikely to be used in the intragonadal environment. The presence
      of a buoyant egg and functional brachiolaria larva would not be expected in an
      intragonadal brooder and indicate the potential for life-history reversal to a
      planktonic existence. Life-history traits of species in the Cryptasterina group
      are compared with those of other asterinids in the genus Patiriella with
      viviparous development. Modifications of life-history traits and pathways
      associated with evolution of viviparity in the Asterinidae are assessed, and the
      presence of convergent adaptations and clade-specific features associated with
      this unusual mode of parental care are examined.

PMID- 14672984
TI  - Persistent ancestral feeding structures in nonfeeding annelid larvae.
AB  - Evolutionary loss of the requirement for feeding in larvae of marine
      invertebrates is often followed by loss of structures involved in capturing and
      digesting food. Studies of echinoderms suggest that larval form evolves rapidly
      in response to loss of the requirement for feeding, but a lack of data from other
      taxa makes it difficult to assess the generality of this result. I show that many
      members of a large clade of annelids, the Sabellidae, retain ancestral systems
      for particle capture despite loss of the need and ability to feed. In at least
      one species, Schizobranchia insignis, an opposed-band system of prototrochal,
      food-groove, and metatrochal ciliary bands can concentrate suspended particles
      and transport them to the mouth, but captured particles are invariably rejected
      because larvae lack a functional gut. The persistence of particle capture systems
      in larvae of sabellids suggests that they have lost larval feeding very recently,
      that opposed bands are inexpensive to construct and operate, or that opposed
      bands have some alternative function. These observations also suggest a
      hypothesis on how the ability to feed is lost in larvae of annelids and other
      spiralians following increases in egg size.

PMID- 14672985
TI  - Cloning, characterization, and developmental expression of a putative farnesoic
      acid O-methyl transferase in the female edible crab Cancer pagurus.
AB  - Farnesoic acid methyl transferase (FAMTase) catalyzes methylation of farnesoic
      acid to yield the crustacean juvenoid, methyl farnesoate (MF). A full-length cDNA
      encoding a 275 amino acid putative FAMTase has been isolated from the mandibular
      organ of the female edible crab (Cancer pagurus) by reverse transcriptase
      polymerase chain reaction in conjunction with cDNA library screening. A high
      degree of sequence identity was found between this and other putative crustacean
      FAMTases. Conceptual translation and protein sequence analysis suggested that
      phosphorylation could occur at multiple sites in the FAMTase. This finding is
      consistent with the recent observation that endogenous FAMTase activity in
      mandibular organ extracts can be regulated by phosphorylation in vitro. We
      demonstrated that the recombinant FAMTase could be expressed as a LacZ-fusion
      protein in Escherichia coli and have undertaken its partial purification from
      inclusion bodies. In an established assay system, the recombinant FAMTase lacked
      activity. Northern blotting demonstrated widespread expression of an
      approximately 1250-nucleotide FAMTase transcript in female C. pagurus tissues.
      Levels of FAMTase transcripts in mandibular organs of female C. pagurus were
      found to fluctuate during vitellogenesis and embryonic development. Throughout
      the spring of 2002, an HPLC-based method was used to measure hemolymph MF titers
      in more than 70 female specimens of C. pagurus, which segregated into "high MF"
      and "low MF" groups. The high MF titers, which occurred before or during early
      vitellogenesis, coincided with, or were preceded by, elevated levels of putative
      FAMTase mRNA in the mandibular organs.

PMID- 14672986
TI  - Determinate growth and modularity in a gorgonian octocoral.
AB  - Growth rates of branches of colonies of the gorgonian Pseudopterogorgia
      elisabethae were monitored for 2 years on a reef at San Salvador Island, Bahamas.
      Images of 261 colonies were made at 6-month intervals and colony and branch
      growth analyzed. Branch growth rates differed between colonies and between the
      time intervals in which the measurements were made. Colonies developed a
      plumelike morphology through a pattern of branch origination and determinate
      growth in which branch growth rates were greatest at the time the branch
      originated and branches seldom grew beyond a length of 8 cm. A small number of
      branches had greater growth rates, did not stop growing, and were sites for the
      origination of subsequent "generations" of branches. The rate of branch
      origination decreased with each generation of branching, and branch growth rates
      were lower on larger colonies, leading to determinate colony growth. Although
      colonial invertebrates like P. elisabethae grow through the addition of polyps,
      branches behave as modules with determinate growth. Colony form and size is
      generated by the iterative addition of branches.

PMID- 14672987
TI  - Possible roles of sulfur-containing amino acids in a chemoautotrophic bacterium
      mollusc symbiosis.
AB  - Invertebrate hosts of chemoautotrophic symbionts face the unique challenge of
      supplying their symbionts with hydrogen sulfide while avoiding its toxic effects.
      The sulfur-containing free amino acids taurine and thiotaurine may function in
      sulfide detoxification by serving as sulfur storage compounds or as transport
      compounds between symbiont and host. After sulfide exposure, both taurine and
      thiotaurine levels increased in the gill tissues of the symbiotic coastal bivalve
      Solemya velum. Inhibition of prokaryotic metabolism with chloramphenicol,
      inhibition of eukaryotic metabolism with cycloheximide, and inhibition of ammonia
      assimilation with methionine sulfoximine reduced levels of sulfur-containing
      amino acids. Chloramphenicol treatment inhibited the removal of sulfide from the
      medium. In the absence of metabolic inhibitors, estimated rates of sulfide
      incorporation into taurine and thiotaurine accounted for nearly half of the
      sulfide removed from the medium. In contrast, amino acid levels in the
      nonsymbiotic, sulfide-tolerant molluscs Geukensia demissa and Yoldia limatula did
      not change after sulfide exposure. These findings suggest that sulfur-containing
      amino acids function in sulfide detoxification in symbiotic invertebrates, and
      that this process depends upon ammonia assimilation and symbiont metabolic
      capabilities.

PMID- 14672988
TI  - Localization of a symbiosis-related protein, Sym32, in the Anthopleura
      elegantissima-Symbiodinium muscatinei Association.
AB  - Cnidarian-dinoflagellate symbioses are widespread in the marine environment.
      Growing concern over the health of coral reef ecosystems has revealed a
      fundamental lack of knowledge of how cnidarian-algal associations are regulated
      at the cellular and molecular level. We are interested in identifying genes that
      mediate interactions between the partners, and we are using the temperate sea
      anemone Anthopleura elegantissima as a model. We previously described a host
      gene, sym32, encoding a fasciclin domain protein, that is differentially
      expressed in symbiotic and aposymbiotic A. elegantissima. Here, we describe the
      subcellular localization of the sym32 protein. In aposymbiotic (symbiont-free)
      hosts, sym32 was located in vesicles that occur along the apical edges of
      gastrodermal cells. In symbiotic hosts, such vesicles were absent, but sym32 was
      present within the symbiosome membranes. Sym32 (or a cross-reactive protein) was
      also present in the accumulation bodies of the symbionts. Although the anti-sym32
      antiserum was not sufficiently specific to detect the target protein in cultured
      Symbiodinium bermudense cells, Western blots of proteins from two Symbiodinium
      species revealed a protein doublet of 45 and 48 kDa, suggesting that the
      symbionts may also produce a fasciclin domain protein. We suggest that host sym32
      is relocated from gastrodermal vesicles to the symbiosome membrane when symbionts
      are taken into host cells by phagocytosis.

PMID- 14672989
TI  - Columellar muscle of neogastropods: muscle attachment and the function of
      columellar folds.
AB  - Malacologists often assume that ornamentation on snail shells is functional, and
      therefore adaptive. I conducted the first comprehensive test of the widely
      accepted hypothesis that columellar folds, a type of internal ornamentation,
      enhance the performance of the columellar muscle, which attaches the snail to its
      shell. Careful dissections of live, non-relaxed specimens reveal that the
      physical attachment between the columellar muscle and the columella is not
      restricted to a small, circular patch located deep within the shell. Instead, the
      attachment is long and narrow, extending approximately a full whorl along the
      length of the columella. I developed a novel technique for preparing three
      dimensional reconstructions from photographs documenting the dissections. These
      reconstructions were then used to measure four parameters that describe the
      muscle: (1) the surface area of the physical attachment between the muscle and
      columella, (2) the total contact area between the muscle and the columella, (3)
      the depth of attachment, and (4) the length of attachment. None of these
      parameters differed significantly between species with and without folds. In
      light of the biomechanics of muscular hydrostats, values of the first parameter
      indicate that columellar folds probably do not guide the columellar muscle as the
      animal moves in and out of its shell. Values of the other parameters indicate
      that columellar folds neither increase an animal's ability to maneuver its shell
      nor facilitate deeper withdrawal. These results, and the fact that folds have
      evolved convergently several times, might indicate that folds are an easily
      evolvable solution to many functional problems, none of which are currently
      understood.

PMID- 14672990
TI  - Response in nematocyst uptake by the nudibranch Flabellina verrucosa to the
      presence of various predators in the Southern Gulf of Maine.
AB  - Aeolid nudibranchs maintain nematocysts sequestered from their cnidarian prey for
      protection against predators. Selection for nematocyst incorporation is a
      function of diet and prey choice, but ratios vary among nudibranchs feeding on a
      given diet, indicating that other factors may be involved. It is proposed that
      the presence of predators influences nematocyst incorporation. Nematocyst uptake
      in the nudibranch Flabellina verrucosa collected from the southern Gulf of Maine
      was examined in response to various potential predators, including Crossaster
      papposus, Tautogolabrus adspersus, and Carcinus maenas. Nudibranchs in individual
      flow-through containers feeding on a diet of the hydroids Tubularia spp. and
      Obelia geniculata were subjected to tanks containing a predator, then their
      nematocyst distribution was examined. Although most of the changes over the
      experimental period were attributable to diet, F. verrucosa responded to both T.
      adspersus and C. papposus by significantly increasing microbasic mastigophore
      incorporation. No differential uptake was seen with C. maenas. Response was
      evident in the nudibranchs both for predators present in the collection area and
      for those with which they had no previous exposure, indicating that F. verrucosa
      modulates nematocyst incorporation in response to the presence of predators as
      well as to diet. A coevolution of nudibranchs and potential predators may govern
      changes in nematocyst uptake.

PMID- 14672992
TI  - Epilepsy-associated dysfunction in the voltage-gated neuronal sodium channel
      SCN1A.
AB  - Mutations in SCN1A, the gene encoding the brain voltage-gated sodium channel
      alpha1 subunit (NaV1.1), are associated with at least two forms of epilepsy,
      generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic
      epilepsy of infancy (SMEI). We examined the functional properties of four GEFS+
      alleles and one SMEI allele using whole-cell patch-clamp analysis of
      heterologously expressed recombinant human SCN1A. One previously reported GEFS+
      mutation (I1656M) and an additional novel allele (R1657C), both affecting
      residues in a voltage-sensing S4 segment, exhibited a similar depolarizing shift
      in the voltage dependence of activation. Additionally, R1657C showed a 50%
      reduction in current density and accelerated recovery from slow inactivation.
      Unlike three other GEFS+ alleles that we recently characterized, neither R1657C
      nor I1656M gave rise to a persistent, noninactivating current. In contrast, two
      other GEFS+ mutations (A1685V and V1353L) and L986F, an SMEI-associated allele,
      exhibited complete loss of function. In conclusion, our data provide evidence for
      a wide spectrum of sodium channel dysfunction in familial epilepsy and
      demonstrate that both GEFS+ and SMEI can be associated with nonfunctional SCN1A
      alleles.

PMID- 14672991
TI  - Surface expression of the netrin receptor UNC5H1 is regulated through a protein
      kinase C-interacting protein/protein kinase-dependent mechanism.
AB  - Netrin-1 is a bifunctional guidance cue that directs migrating neurons and axons
      based on specific receptors expressed on the cell surface. Attraction occurs
      through the receptor Deleted in Colorectal Cancer (DCC) and repulsion occurs
      through a receptor complex of DCC and UNC5H, the vertebrate homolog to
      Caenorhabditis elegans UNC-5, but how the specific surface expression of these
      receptors is achieved remains unknown. Here, we demonstrate that surface
      expression of UNC5H1 is regulated in neurons by protein interacting with C kinase
      1 (PICK1) and protein kinase C (PKC), and show that one mechanism by which cells
      control their response to netrin-1 is by changing the surface availability of
      receptors. We identified PICK1 as a binding partner for UNC5H1 using the yeast
      two-hybrid system and found that the extreme three C-terminal amino acids of
      UNC5H1 interact with the PSD-95/Dlg/ZO-1 (PDZ) domain of PICK1. Coexpression of
      UNC5H1 and PICK1 in heterologous cells results in the recruitment of PICK1 to
      UNC5H1 clusters. Endogenous UNC5H1 and PICK1 coimmunoprecipitate from extracts of
      cultured hippocampal neurons and P4 cortices, and immunohistochemistry shows that
      UNC5H1, PICK1, and PKC are all present in growth cones. PKC activation induces
      the formation of UNC5H1/PICK1/PKC complexes and leads to the specific removal of
      UNC5H1, but not DCC, from the surface of neurons and growth cones via a PICK1/PKC
      dependent mechanism. Lastly, we demonstrate that activating PKC, which decreases
      surface expression of UNC5H1, inhibits netrin-1-dependent collapse of hippocampal
      growth cones. Together, our results suggest that by regulating the surface
      expression of UNC5Hs, an axon can modulate its repellent response to netrin-1.

PMID- 14672993
TI  - Comparative distribution of glutamate transporters and receptors in relation to
      afferent innervation density in the mammalian cochlea.
AB  - The local expression of proteins involved in handling glutamate may be regulated
      by the number and activity of synapses in regions of glutamatergic innervation.
      The systematically varying innervation of inner hair cells (IHCs) of the cochlea
      provides a model to test this suggestion. IHCs are glutamatergic and form a
      single row along the cochlear spiral. Along this row the number of afferent
      fibers terminating on IHCs increases toward the base, reaching a peak and
      thereafter declining. The afferents are segregated so that higher spontaneous
      rate fibers terminate on the pillar-cell side of the IHC and lower rate fibers
      terminate on the modiolar side. Using immunofluorescence and postembedding
      immunogold labeling, we investigated the distributions of the glutamate-aspartate
      transporter (GLAST or excitatory amino acid transporter 1), vesicular glutamate
      transporter (VGLUT1), and the AMPA receptor glutamate receptor 4 (GluR4) along
      the spiral. Immunofluorescent labeling for GLAST in IHC supporting cells
      increased in intensity to a peak in the region of 6-9 mm from the apex.
      Immunogold labeling for GLAST was greater overall in these cells in the 10 mm
      region than in the 1 mm region and also on the pillar-cell side of the IHC
      compared with the modiolar side. Immunogold labeling for GluR4 was confined to
      synaptic sites, represented by puncta in immunofluorescence. The relative numbers
      of puncta changed with a gradient similar to that of GLAST labeling. VGLUT1
      labeling occurred in IHCs but showed no clear cochleotopic gradient. These data
      suggest that both the density of innervation and the activity levels of
      glutamatergic synapses may be involved in modulating regional expression of
      GLAST.

PMID- 14672994
TI  - Shared response preparation for pursuit and saccadic eye movements.
AB  - Tracking a single target in the visual world requires coordination between
      pursuit and saccadic eye movements. The constraints imposed on pursuit and
      saccade decisions by visual processing and response preparation are difficult to
      compare because latency differences between the two movements provide different
      amounts of visual sampling time. The present study compares pursuit and saccade
      decisions when visual processing was directly manipulated. Human observers were
      asked to select between two stationary stimuli presented simultaneously at two
      different locations based on which had the higher contrast. The stimuli were
      presented for a brief, variable interval and then occluded by masks. Because the
      masks moved horizontally and were offset vertically, subjects were obliged to
      make both pursuit and saccadic eye movements to track the mask covering the
      target stimulus. For each of the exposure durations, we constructed oculometric
      curves for pursuit and saccades. We found that both systems had similar
      oculometric thresholds and response biases. The initial pursuit decisions
      differed from the subsequent saccade decisions on 1-13% of the trials but were
      the same more often than predicted by independent mechanisms. Moreover, pursuit
      reversed direction on discordant trials, so that the pursuit decision always
      matched that of the saccade by the time the saccade was started. These results
      support the view that, in addition to overlap in early visual areas and the final
      motor pathways, the pursuit and saccadic systems share processing at the level of
      response preparation. This shared processing may help ensure the coordination of
      pursuit and saccadic eye movements in selecting a single target.

PMID- 14672995
TI  - Pivotal role of nucleotide P2X2 receptor subunit of the ATP-gated ion channel
      mediating ventilatory responses to hypoxia.
AB  - In mammals, the ventilatory response to decreased oxygen tension in the arterial
      blood is initiated by excitation of specialized O2-sensitive chemoreceptor cells
      in the carotid body that release neurotransmitters to activate endings of the
      sinus nerve afferent fibers. We investigated the role of ATP acting via
      ionotropic P2X receptors in the carotid body function and ventilatory response to
      hypoxia in mice. Mice deficient in P2X2 receptor subunit showed a markedly
      attenuated ventilatory response to hypoxia, whereas the response to hypoxia in
      P2X3-deficient mice was comparable with that seen in wild-type controls. P2X2 and
      P2X3 receptor subunit deficiency did not affect the ventilatory responses to
      hypercapnia. P2X2 subunit deficiency resulted in a dramatic reduction in the
      responses of the carotid sinus nerve to hypoxia in the in vitro carotid body
      sinus nerve preparation. ATP and its stable analog alpha,beta-methyleneATP both
      evoked rapid excitation of sinus nerve afferents, and the P2 receptor antagonist
      PPADS (pyridoxal-5'-phosphate-6-azophenyl-2',4'-disulphonic acid) (100 microm)
      blocked hypoxia-induced increase in sinus nerve discharge. Immunoreactivities for
      P2X2 and P2X3 subunits were both detected on afferent terminals surrounding
      clusters of glomus cells in the wild-type animals but were absent in mice
      deficient in P2X2 and P2X3 receptor subunits. These observations provide the
      first definitive evidence that, in the carotid body, ATP is a key transmitter
      released by chemoreceptor cells to activate endings of the sinus nerve afferent
      fibers. We conclude that P2X receptors containing the P2X2 subunit play a pivotal
      role in carotid body function and in mediating ventilatory responses to hypoxia.

PMID- 14672996
TI  - Selective activation induced cleavage of the NR2B subunit by calpain.
AB  - Although activation of calcium-activated neutral protease (calpain) by the NMDA
      receptor has been suggested to play critical roles in synaptic modulation and
      neurologic disease, the nature of its substrates has not been completely defined.
      In this study, we examined the ability of calpain to cleave the NMDA receptor in
      cultured hippocampal neurons. Activation of the NMDA receptor by agonist
      application led to rapid calpain-specific proteolysis of spectrin and decreased
      levels of NR2A/2B subunits. Cleavage of the NR2A/2B subunit created a 115 kDa
      product that retained the ability to bind 125I-MK-801 and is predicted to be
      active. Increases in levels of this product appeared within 5 min of NMDA
      receptor activation and were stable for periods of >30 min. Subtype-specific
      antibodies demonstrated that the NR2B subunit was cleaved in these primary
      cultures, but the NR2A subunit was not. An inhibitor of calpain blocked both the
      decrease of intact NR2B and the increase of the low molecular weight form,
      whereas neither caspase nor cathepsin inhibitors had an effect on these events.
      Cell surface biotinylation experiments demonstrated that the 115 kDa fragment
      remained on the cell surface. This NR2B fragment was also found in the rat
      hippocampus after transient forebrain ischemia, showing that this process also
      occurs in vivo. This suggests that calpain-mediated cleavage of the NR2B subunit
      occurs in neurons and gives rise to active NMDA receptor forms present on the
      cell surface after excitotoxic glutamatergic stimulation. Such forms could
      contribute to excitotoxicity and synaptic remodeling.

PMID- 14672997
TI  - Synaptic cleft acidification and modulation of short-term depression by
      exocytosed protons in retinal bipolar cells.
AB  - The release of vesicular protons during exocytosis causes a feedback inhibition
      of Ca2+ channels in photoreceptor terminals; however, the effect of this
      inhibition on subsequent exocytosis has not been studied. Here we show that a
      similar L-type Ca2+ channel inhibition occurs in bipolar cell terminals in slices
      of goldfish retina, and we investigate the effect that this has on subsequent
      exocytosis with membrane capacitance measurements. We find that transient Ca2+
      current inhibition is correlated with exocytosis and modulated by the
      concentration of extracellular pH buffer. Ca2+ current inhibition is negligible
      in acutely dissociated terminals, demonstrating the importance of an intact
      synaptic cleft. The sensitivity of bipolar cell Ca2+ currents to extracellular pH
      was assessed: channel conductance is reduced and activation is shifted to more
      positive potentials by acidification. The effect of Ca2+ current inhibition on
      subsequent exocytosis was investigated by measuring paired-pulse depression.
      Under conditions in which there is a large amount of inhibition of Ca2+ influx,
      the degree of paired-pulse depression is significantly reduced. Finally, we show
      that under physiological (bicarbonate) buffering conditions, pronounced Ca2+
      current inhibition occurs after exocytosis ( approximately 60% peak inhibition),
      which can decrease subsequent exocytosis during single depolarizations. We
      estimate that exocytosis is accompanied by a transient change in synaptic cleft
      pH from 7.5 to approximately 6.9. We suggest that this effect serves as an
      activity-dependent modulator of exocytosis at ribbon-type synapses where a large
      and compact coterie of vesicles can fuse at each active zone.

PMID- 14672998
TI  - Mediolateral compartmentalization of the cerebellum is determined on the "birth
      date" of Purkinje cells.
AB  - The adult cerebellum is functionally compartmentalized into clusters along the
      mediolateral axis (M-L clusters), and a variety of molecular makers are expressed
      in specific subsets of M-L clusters. These M-L clusters appear to be the basic
      structure in which cerebellar functions are performed, but the mechanisms by
      which cerebellar mediolateral compartmentalization is established are still
      unclear. To address these questions, we examined the development of M-L clusters
      using replication-defective adenoviral vectors. The adenoviral vectors
      effectively introduced foreign genes into the neuronal progenitor cells of the
      cerebellum in a birth date-specific manner, allowing us to observe the native
      behavior of each cohort of birth date-related progenitor cells. When the
      adenoviral vectors were injected into the midbrain ventricle of mouse embryos on
      embryonic days 10.5 (E10.5), E11.5, and E12.5, the virally infected cerebellar
      progenitor cells developed into Purkinje cells. Notably, the Purkinje cells that
      shared the same birth date formed specific subsets of M-L clusters in the
      cerebellum. Each subset of M-L clusters displayed nested and, in part, mutually
      complementary patterns, and these patterns were unchanged from the late embryonic
      stage to adulthood, suggesting that Purkinje cell progenitors are fated to form
      specific subsets of M-L clusters after their birth between E10.5 and E12.5. This
      study represents the first such direct observation of Purkinje cell development.
      Moreover, we also show that there is a correlation between the M-L clusters
      established by the birth date-related Purkinje cells and the domains of engrailed
      2, Wnt-7B, L7/pcp2, and EphA4 receptor tyrosine kinase expression.

PMID- 14672999
TI  - Activity-dependent depression of excitability and calcium transients in the
      neurohypophysis suggests a model of "stuttering conduction".
AB  - Using millisecond time-resolved optical recordings of transmembrane voltage and
      intraterminal calcium, we have determined how activity-dependent changes in the
      population action potential are related to a concurrent modulation of calcium
      transients in the neurohypophysis. We find that repetitive stimulation
      dramatically alters the amplitude of the population action potential and
      significantly increases its temporal dispersion. The population action potentials
      and the calcium transients exhibit well correlated frequency-dependent amplitude
      depression, with broadening of the action potential playing only a limited role.
      High-speed camera recordings indicate that the magnitude of the spike modulation
      is uniform throughout the neurohypophysis, thereby excluding propagation failure
      as the underlying mechanism. In contrast, temporal dispersion and latency of the
      population spike do increase with distance from the stimulation site. This
      increase is enhanced during repeated stimulation and by raising the stimulation
      frequency. Changes in Ca influx directly affect the decline in population spike
      amplitude, consistent with electrophysiological measurements of the local loss of
      excitability in nerve terminals and varicosities, mediated by a Ca-activated K
      conductance. Our observations suggest a model of "stuttering conduction":
      repeated action potential stimulation causes excitability failures limited to
      nerve terminals and varicosities, which account for the rapid decline in the
      population spike amplitude. These failures, however, do not block action
      potential propagation but generate the cumulative increases in spike latency.

PMID- 14673000
TI  - Action potential initiation and propagation in layer 5 pyramidal neurons of the
      rat prefrontal cortex: absence of dopamine modulation.
AB  - Somatic and dendritic whole-cell recording was used to examine action potential
      (AP) initiation and propagation in layer 5 pyramidal neurons of the rat prelimbic
      prefrontal cortex. APs generated by somatic current injection, or via antidromic
      stimulation, were reliably recorded at apical dendritic locations as far as 480
      microm from the soma. Although the backpropagation of single APs into the apical
      dendrite was robust, frequency-dependent attenuation was observed during AP
      trains delivered at 10-100 Hz. APs were usually initiated close to the soma
      (presumably in the axon); however, strong depolarizing input to the apical
      dendrite could generate dendritic spikes that preceded somatic APs. AP
      backpropagation was dependent solely on activation of dendritic voltage-gated
      sodium channels and did not require activation of dendritic calcium channels.
      Despite not playing a role in AP backpropagation, calcium-imaging experiments
      demonstrated that dendritic calcium channels are activated by backpropagating
      APs, leading to transient increases in intracellular calcium. In addition,
      calcium imaging revealed that AP backpropagation into the distal apical tuft was
      frequency dependent. Finally, we tested whether dopamine, a prominent
      neuromodulator associated with prefrontal activity, could alter AP initiation or
      backpropagation. Bath-applied dopamine (10 or 100 microm) did not effect AP
      backpropagation, frequency-dependent depression, local dendritic spike
      initiation, or AP-induced calcium signaling. These data indicate that AP
      backpropagation in prefrontal layer 5 pyramidal neurons is robust but frequency
      dependent in the distal tuft, requires dendritic sodium rather than calcium
      channel activation, and, unlike other aspects of neuronal excitability,
      insensitive to modulation by dopamine.

PMID- 14673002
TI  - Plasticity of GABA(B) receptor-mediated heterosynaptic interactions at mossy
      fibers after status epilepticus.
AB  - Several neurotransmitters, including GABA acting at presynaptic GABA(B)
      receptors, modulate glutamate release at synapses between hippocampal mossy
      fibers and CA3 pyramidal neurons. This phenomenon gates excitation of the
      hippocampus and may therefore prevent limbic seizure propagation. Here we report
      that status epilepticus, triggered by either perforant path stimulation or
      pilocarpine administration, was followed 24 hr later by a loss of GABA(B)
      receptor-mediated heterosynaptic depression among populations of mossy fibers.
      This was accompanied by a decrease in the sensitivity of mossy fiber transmission
      to the exogenous GABA(B) receptor agonist baclofen. Autoradiography revealed a
      reduction in GABA(B) receptor binding in the stratum lucidum after status
      epilepticus. Failure of GABA(B) receptor-mediated modulation of mossy fiber
      transmission at mossy fibers may contribute to the development of spontaneous
      seizures after status epilepticus.

PMID- 14673001
TI  - Apoptosis induced by p75NTR overexpression requires Jun kinase-dependent
      phosphorylation of Bad.
AB  - The p75 neurotrophin receptor (p75NTR), a member of the tumor necrosis factor
      receptor superfamily, facilitates apoptosis during development and after injury
      to the CNS. The signaling cascades activated by p75NTR that result in apoptosis
      remain poorly understood. In this study, we show that overexpression of p75NTR in
      primary cortical neurons, in pheochromocytoma cell line (PC12) cells, and in
      glioma cells results in activation of Jun kinase (JNK), accumulation of
      cytochrome c within the cytosol, and activation of caspases 9, 6, and 3. To link
      p75NTR-dependent JNK activation to mitochondrial cytochrome c release, regulation
      of BH3-domain-only family members was examined. Transcription of BH3-domain-only
      family members was not induced by p75NTR, but p75NTR-dependent JNK activation
      resulted in phosphorylation and oligomerization of the BH3-domain-only family
      member Bad. Loss of function experiments using Bad dominant negatives or RNA
      interference demonstrated a requirement for Bad in p75NTR-induced apoptosis.
      Together, these studies provide the first data linking apoptosis induced by
      p75NTR to the phosphorylation of BH3-domain-only family members.

PMID- 14673003
TI  - Effects of spontaneous eye movements on spatial memory in macaque periarcuate
      cortex.
AB  - Persistent activity in prefrontal cortex during delayed response tasks is a
      putative neural correlate of spatial working memory. We tested whether this
      activity was sensitive to eye movements made during the memory interval by
      recording from prefrontal neurons while monkeys performed a delayed spatial
      matching saccade task in which they were allowed to make eye movements freely. We
      found that eye movements degraded the spatial tuning of persistent activity even
      as there was an improvement in behavioral performance. Although the strength of
      the memory signal decreased, delay activity continued to signal the location of
      cue. The results suggest that free eye movements reduce neuronal gain rather than
      add variability. The saccades performed during the delay suggest the existence of
      a rehearsal mechanism that could contribute to working memory maintenance. The
      results do not provide support for a segregation of storage and executive
      functions in the periarcuate cortex.

PMID- 14673004
TI  - Imaging reveals synaptic targets of a swim-terminating neuron in the leech CNS.
AB  - In the leech, the command-like neuron called cell Tr2 is known to stop swimming,
      but the connections from cell Tr2 to the swim central pattern generator have not
      been identified. We used fluorescence resonance energy transfer voltage-sensitive
      dyes to identify three neurons that are synaptic targets of cell Tr2. We then
      used electrophysiological techniques to show that these connections are
      monosynaptic, chemical, and excitatory. Two of the novel targets, cell 256 and
      cell 54, terminate swimming when stimulated. These neurons are likely to mediate
      swim cessation caused by cell Tr2 activity, and thus play the role of
      intermediate control cells in the leech CNS.

PMID- 14673005
TI  - Treadmill locomotion in the intact and spinal mouse.
AB  - Because the genetic characteristics of several inbred strains of mice are well
      identified, their use is becoming increasingly popular in spinal cord injury
      research. In this context, it appears particularly important to document
      adequately motor patterns, such as locomotion in normal mice, to establish some
      baseline values of locomotor characteristics. It also seems crucial to determine
      the extent to which mice can express a locomotor pattern after a complete spinal
      transection to establish a baseline on which one can evaluate the effects of
      treatments after spinal injury. Therefore, we have used conventional techniques
      to document the kinematics of treadmill locomotion in intact mice (n = 11) and in
      mice with a complete section of the spinal cord at T8 (n = 12). The results show
      that the kinematics and EMG of adult normal mice can be adequately monitored with
      such conventional equipment and that mice can re-express hindlimb locomotion
      within 14 d after spinalization, without any pharmacological treatments. The
      angular excursions of the hip, knee, and ankle are similar to those of the intact
      mice, although the joints are sometimes more flexed. After spinal cord
      transection, out-of-phase alternation between the homologous limbs recovered,
      whereas the timing between homolateral limbs was completely lost. This remarkable
      ability of mice to express hindlimb locomotion after a complete spinalization
      should be taken into account in the evaluation of various procedures aimed at
      promoting the functional recovery of locomotion after spinal lesions.

PMID- 14673006
TI  - Estradiol attenuates programmed cell death after stroke-like injury.
AB  - Estradiol is a known neurotrophic and neuroprotective factor. Our previous work
      demonstrated that replacement with physiological concentrations of estradiol
      protects the cortex against middle cerebral artery occlusion (MCAO)-induced cell
      death. The cerebral cortex exhibits caspase-dependent programmed cell death (PCD)
      in many models of focal cerebral ischemia. We hypothesized that estradiol
      attenuates PCD during stroke injury. The current study explored the
      temporospatial pattern of markers of PCD, their relationship to the evolution of
      injury, and their modulation by estradiol. Rats were ovariectomized and treated
      with either estradiol or vehicle. One week later, rats underwent MCAO, and brains
      were collected at 1, 4, 8, 16, and 24 hr. We assessed the temporospatial
      evolution of infarction volume, DNA fragmentation, and levels of spectrin
      cleavage products in ischemic cortex. Estradiol led to a delay and attenuation of
      injury-mediated DNA fragmentation as early as 8 hr after MCAO. Estradiol also
      dramatically reduced the level of the 120 kDa caspase-mediated spectrin breakdown
      product (SBDP120) at 4 hr but not at 8 or 16 hr. The SBDP150, produced by caspase
      and calpain, showed peak levels at 16 hr but was not altered by estradiol. These
      results strongly suggest that estradiol protects the ischemic cortex by
      attenuating PCD, thereby reducing caspase activity, DNA fragmentation, and
      subsequently, overall cell death. These studies deepen our understanding of the
      mechanisms underlying estrogen-mediated neuroprotection.

PMID- 14673007
TI  - 12-lipoxygenase metabolites of arachidonic acid mediate metabotropic glutamate
      receptor-dependent long-term depression at hippocampal CA3-CA1 synapses.
AB  - Arachidonic acid metabolites have been proposed as signaling molecules in
      hippocampal long-term potentiation (LTP) and long-term depression (LTD) for >15
      years. However, the functional role of these molecules remains controversial.
      Here we used a multidisciplinary biochemical, electrophysiological, and genetic
      approach to examine the function of the 12-lipoxygenase metabolites of
      arachidonic acid in long-term synaptic plasticity at CA3-CA1 synapses. We found
      that the 12-lipoxygenase pathway is required for the induction of metabotropic
      glutamate receptor-dependent LTD (mGluR-LTD), but is not required for LTP: (1)
      Hippocampal homogenates were capable of synthesizing the 12-lipoxygenase
      metabolite of arachidonic acid, 12(S)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid
      (HETE). (2) Stimulation protocols that induce mGluR-LTD lead to a release of 12
      (S)-HETE from acute hippocampal slices. (3) A mouse in which the leukocyte-type
      12-lipoxygenase (the neuronal isoform) was deleted through homologous
      recombination was deficient in mGluR-LTD, but showed normal LTP. (4)
      Pharmacological inhibition of 12-lipoxygenase also blocked induction of mGluR
      LTD. (5) Finally, direct application of 12(S)-HPETE, but not 15(S)-HPETE, to
      hippocampal slices induced a long-term depression of synaptic transmission that
      mimicked and occluded mGluR-LTD induced by synaptic stimulation. Thus, 12(S)
      hydroperoxyeicosa-5Z, 8Z, 10E, 14Z-tetraenoic acid (12(S)-HPETE), a 12
      lipoxygenase metabolite of arachidonic acid, satisfies all of the criteria of a
      messenger molecule that is actively recruited for the induction of mGluR-LTD.

PMID- 14673008
TI  - Mitogen-activated protein kinase signaling in the hippocampus and its modulation
      by corticotropin-releasing factor receptor 2: a possible link between stress and
      fear memory.
AB  - A coordinated activation of multiple interlinked signaling pathways involving
      cAMP-dependent protein kinase (PKA) and mitogen-activated extracellular signal
      regulated kinases (Mek-1/2) regulates gene expression and neuronal changes
      underlying memory consolidation. In the present study we investigated whether
      these molecular cascades might mediate the effects of stress on memory formation.
      We also investigated the role of hippocampal corticotropin-releasing factor
      receptor 2 (CRF2) in stress-enhanced learning and molecular signaling mediated by
      PKA, Mek-1/2, and their downstream targets extracellularly regulated kinases 1
      and 2 (Erk-1/2) and p90-ribosomal-s-kinase-1 (p90Rsk-1). Acute 1 hr
      immobilization was used as a stressful stimulus, and one-trial context-dependent
      fear conditioning was used as a model for associative learning. Training of
      BALB/c mice 3 hr after the end of immobilization resulted in an enhancement of
      conditioned fear, as indicated by significantly increased freezing behavior of
      stressed when compared with nonstressed mice. Interestingly, Erk-1/2
      phosphorylation after conditioning of nonstressed and stressed mice depended on
      PKA and Mek-1/2, respectively. Intrahippocampal injection of the selective Mek
      1/2 inhibitor U0126 or CRF2 antagonist antisauvagine-30 (aSvg-30) prevented
      stress-enhanced fear conditioning and Mek-1/2-dependent activation of Erk-1/2 and
      p90Rsk-1. aSvg-30 did not affect the phosphorylation of the PKA regulatory
      subunit II of stressed mice. The molecular and behavioral effects of CRF2
      coincided with stress-induced upregulation of CRF2 mRNA. These results suggest
      that modulation of Mek-1/2-dependent signaling by hippocampal CRF2 can be
      selectively involved in the delayed effects of stress on memory consolidation.

PMID- 14673010
TI  - Oxidative stress is responsible for deficient survival and dendritogenesis in
      purkinje neurons from ataxia-telangiectasia mutated mutant mice.
AB  - Atm gene-disrupted mice recapitulate the majority of characteristics observed in
      patients with the genetic disorder ataxia-telangiectasia (A-T). However, although
      they exhibit defects in neuromotor function and a distinct neurological
      phenotype, they do not show the progressive neurodegeneration seen in human
      patients, but there is evidence that ataxia-telangiectasia mutated (Atm)
      deficient animals have elevated levels of oxidized macromolecules and some
      neuropathology. We report here that in vitro survival of cerebellar Purkinje
      cells from both Atm "knock-out" and Atm "knock-in" mice was significantly reduced
      compared with their wild-type littermates. Although most of the Purkinje neurons
      from wild-type mice exhibited extensive dendritic elongation and branching under
      these conditions, most neurons from Atm-deficient mice had dramatically reduced
      dendritic branching. An antioxidant (isoindoline nitroxide) prevented Purkinje
      cell death in Atm-deficient mice and enhanced dendritogenesis to wild-type
      levels. Furthermore, administration of the antioxidant throughout pregnancy had a
      small enhancing effect on Purkinje neuron survival in Atm gene-disrupted animals
      and protected against oxidative stress in older animals. These data provide
      strong evidence for a defect in the cerebellum of Atm-deficient mice and suggest
      that oxidative stress contributes to this phenotype.

PMID- 14673009
TI  - Reduced expression of P2Y1 receptors in connexin43-null mice alters calcium
      signaling and migration of neural progenitor cells.
AB  - Glial calcium signals play important roles during CNS development. Calcium
      transients induced by ATP, acting on purinergic receptors, stimulate DNA
      synthesis, increase astrocytic and neural stem cell proliferation, and are
      prominent during the differentiation of radial glia. We have shown previously
      that expression of P2Y receptors in astrocytes is altered when connexin43 (Cx43)
      is downregulated. To evaluate the consequences of Cx43 deletion on calcium
      signaling during neural progenitor development, studies were performed on
      neurospheres derived from embryonic striatum. After adhesion, cells migrating
      from wild-type (WT) and Cx43-null neurospheres displayed spontaneous calcium
      oscillations. Such activity was blunted by apyrase, 2'-deoxy-N6-methyladenosine
      3',5'-bisphosphate (MRS-2179), and suramin, suggesting that ATP released by
      neural cells acts on purinergic receptors to induce calcium oscillations. The
      amplitudes of Ca2+ transients induced by P2Y but not P2X receptor agonists were
      larger in WT than in Cx43-null progenitors, suggesting that these two cell
      populations express different P2 receptors. Suramin, a nonselective P2 receptor
      antagonist, and MRS-2179, a P2Y1 receptor-selective antagonist, reduced the
      proliferation rate and the migration of WT progenitor cells to levels similar to
      those of Cx43-null cells. Conversely, exogenous expression of P2Y1 receptors in
      Cx43-null cells restored their migration pattern to levels seen in WT
      progenitors. However, treatment with P2 receptor antagonists did not alter the
      ratio of nestin to GFAP expression in WT neural progenitors. These data show that
      altered autocrine-paracrine communication attributable to reduced levels of P2Y1
      receptors in neural progenitor cells lacking Cx43 affects proliferation and
      migration but not cell differentiation during early CNS development.

PMID- 14673011
TI  - Expectation enhances the regional brain metabolic and the reinforcing effects of
      stimulants in cocaine abusers.
AB  - The reinforcing effects of drugs of abuse result from the complex interaction
      between pharmacological effects and conditioned responses. Here we evaluate how
      expectation affects the response to the stimulant drug methylphenidate in 25
      cocaine abusers. The effects of methylphenidate (0.5 mg/kg, i.v.) on brain
      glucose metabolism (measured by [18F]deoxyglucose-positron emission tomography)
      and on its reinforcing effects (self-reports of drug effects) were evaluated in
      four conditions: (1) expecting placebo and receiving placebo; (2) expecting
      placebo and receiving methylphenidate; (3) expecting methylphenidate and
      receiving methylphenidate; (4) expecting methylphenidate and receiving placebo.
      Methylphenidate increased brain glucose metabolism, and the largest changes were
      in cerebellum, occipital cortex, and thalamus. The increases in metabolism were
      approximately 50% larger when methylphenidate was expected than when it was not,
      and these differences were significant in cerebellum (vermis) and thalamus. In
      contrast, unexpected methylphenidate induced greater increases in left lateral
      orbitofrontal cortex than when it was expected. Methylphenidate-induced increases
      in self-reports of "high" were also approximately 50% greater when subjects
      expected to receive it than when they did not and were significantly correlated
      with the metabolic increases in thalamus but not in cerebellum. These findings
      provide evidence that expectation amplifies the effects of methylphenidate in
      brain and its reinforcing effects. They also suggest that the thalamus, a region
      involved with conditioned responses, may mediate the enhancement of the
      reinforcing effects of methylphenidate by expectation and that the orbitofrontal
      cortex mediates the response to unexpected reinforcement. The enhanced cerebellar
      activation with expectation may reflect conditioned responses that are not linked
      to conscious responses.

PMID- 14673012
TI  - Pathway-specific action of gamma-hydroxybutyric acid in sensory thalamus and its
      relevance to absence seizures.
AB  - The systemic injection of gamma-hydroxybutyric acid (GHB) elicits spike and wave
      discharges (SWDs), the EEG hallmark of absence seizures, and represents a well
      established, widely used pharmacological model of this nonconvulsive epilepsy.
      Despite this experimental use of GHB, as well as its therapeutic use in
      narcolepsy and its increasing abuse, however, the precise cellular mechanisms
      underlying the different pharmacological actions of this drug are still unclear.
      Because sensory thalamic nuclei play a key role in the generation of SWDs and
      sleep rhythms, and because direct injection of GHB in the ventrobasal (VB)
      thalamus elicits SWDs, we investigated GHB effects on corticothalamic EPSCs and
      GABAergic IPSCs in VB thalamocortical (TC) neurons. GHB (250 microm-10 mm)
      reversibly decreased the amplitude of electrically evoked EPSCs and GABAA IPSCs
      via activation of GABAB receptors; however, approximately 60% of the IPSCs were
      insensitive to low (250 microm-1.0 mm) GHB concentrations. The putative GHB
      receptor antagonist NSC 382 applied alone had a number of unspecific effects,
      whereas it either had no action on, or further increased, the GHB-elicited
      effects on synaptic currents. Low GHB concentrations (250 microm) were also
      effective in increasing absence-like intrathalamic oscillations evoked by
      cortical afferent stimulation. These results indicate that low concentrations of
      GHB, similar to the brain concentrations that evoke SWDs in vivo, differentially
      affect excitatory and inhibitory synaptic currents in TC neurons and promote
      absence-like intrathalamic oscillations. Furthermore, the present data strengthen
      previous suggestions on the GHB mechanism of sleep promotion and will help focus
      future studies on the cellular mechanisms underlying its abuse.

PMID- 14673013
TI  - Effects of neurotoxic and neuroprotective agents on peripheral nerve regeneration
      assayed by time-lapse imaging in vivo.
AB  - A direct histological assay of axonal regeneration would have many advantages
      over currently available behavioral, electrophysiological, and radiometric
      assays. We show that peripheral sensory axons marked with the yellow fluorescent
      protein in transgenic mice can be viewed transcutaneously in superficial nerves.
      Degenerating and regenerating axons can be followed in live animals with a
      dissecting microscope and then, after fixation, studied at high resolution by
      confocal microscopy. Using this approach, we document differences in regenerative
      ability after nerve transection, crush injury, and crush injury after a previous
      "conditioning" lesion. We also show that the chemotherapeutic drug vincristine
      rapidly but transiently blocks regeneration and that the immunosuppressive drug
      FK506 modestly enhances regeneration. Moreover, FK506 nearly restores normal
      regenerative ability in animals treated with submaximal doses of vincristine.
      Because neuropathy is the major dose-limiting side effect of vincristine, we
      propose that its efficacy could be enhanced by coadministration of FK506 analogs
      that are neuroactive but not immunosuppressive.

PMID- 14673014
TI  - In situ demonstration of dendritic cell migration from rat intestine to
      mesenteric lymph nodes: relationships to maturation and role of chemokines.
AB  - Dendritic cells (DCs) are continuously transported from the intestine to
      mesenteric lymph nodes (MLNs). The objective of this study was to determine the
      migration kinetics of DCs via intestinal lymph and to investigate regulatory
      factors affecting their migration in vivo. DCs were obtained from spleen or
      thoracic duct lymph of mesenteric lymphadenectomized rats. The DCs were
      fluorescently labeled and injected into the subserosa of the small intestine near
      the cecum, and their migration patterns into MLNs were determined. Isolated DCs
      from intestinal lymph express intercellular adhesion molecule-1 (ICAM-1),
      CD11b/c, CD80/86, and major histocompatibility complex class II but maintain
      their ability to phagocytize latex particles, suggesting the presence of immature
      DCs. The isolated DCs accumulated in MLNs in a time-dependent manner with maximal
      accumulation at 48 h. Cytokine-induced maturation of lymph DCs did not cause a
      change in cell number but accelerated their transport into MLNs with a maximum at
      24 h. Splenic DCs showed an intermediate level of maturation and a migration
      pattern similar to mature DCs. Inhibition of ICAM-1 or CD11b/c did not affect DC
      migration. Migration of mature DCs to MLNs was specifically blocked by
      desensitization of CCR7 with CCL21. In contrast, freshly isolated lymph DCs were
      not chemotactic for CCL21, but their migration to MLNs was mainly inhibited by
      desensitization of CCR6 with CCL20. The migratory ability of DCs correlates well
      with their degree of maturation, and different chemokine/chemokine receptor use
      may be the main regulator of DC migration kinetics through intestinal lymph.

PMID- 14673015
TI  - Constitutive and regulated expression of platelet basic protein in human
      monocytes.
AB  - Platelet basic protein (PBP) and several of its derivatives are known for their
      broad range of functions as signaling molecules and cationic antimicrobial
      peptides and were considered hitherto megakaryocyte- and platelet-specific. In
      search of glucocorticoid-regulated antimicrobial systems of monocytes, we found a
      15-fold down-regulation of PBP mRNA by differential display. Regulation was
      confirmed in vivo even at low prednisone doses. Quantitative mRNA analyses
      confirmed down-regulation also for platelets. Western blotting and immunostains
      showed down-regulation at the protein level. Pro-PBP derivatives were in the size
      range of 7.5-14 kD and in immunostains, gave granular cytoplasmatic patterns.
      Interleukin (IL)-4 and IL-10 induced a similar down-regulation. Phagocytosis
      resulted in an increase of smaller derivatives in the range of 7.5 kD.
      Stimulation with interferon-gamma and lipopolysaccharide did decrease expression
      of PBP and affected derivatization. Expression of PBP and its derivatives is not
      restricted to the megakaryocytic cell lineage. PBP and some of its derivatives
      might contribute to the antimicrobial armamentarium of mononuclear phagocytes or
      have monokine functions. Our studies define PBPs as one among the many
      immunosuppressive targets of glucocorticoids.

PMID- 14673016
TI  - Critical role of CXC chemokines in endotoxemic liver injury in mice.
AB  - Tissue accumulation of leukocytes constitutes a rate-limiting step in endotoxin
      induced tissue injury. Chemokines have the capacity to regulate leukocyte
      trafficking. However, the role of CXC chemokines, i.e., macrophage inflammatory
      protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC), in
      leukocyte recruitment, microvascular perfusion failure, cellular injury, and
      apoptosis in the liver remains elusive. Herein, mice were challenged with
      lipopolysaccharide (LPS) in combination with D-galactosamine, and intravital
      microscopy of the liver microcirculation was conducted 6 h later. It was found
      that immunoneutralization of MIP-2 and KC did not reduce LPS-induced leukocyte
      rolling and adhesion in postsinusoidal venules. In contrast, pretreatment with
      monoclonal antibodies against MIP-2 and KC abolished (83% reduction)
      extravascular recruitment of leukocytes in the livers of endotoxemic mice.
      Notably, endotoxin challenge increased the expression of CXC chemokines, which
      was mainly confined to hepatocytes. Moreover, endotoxin-induced increases of
      liver enzymes and hepatocellular apoptosis were decreased by more than 82% and
      68%, respectively, and sinusoidal perfusion was restored in mice passively
      immunized against MIP-2 and KC. In conclusion, this study indicates that
      intravascular accumulation of leukocytes in the liver is independent of CXC
      chemokines in endotoxemic mice. Instead, our novel data suggest that CXC
      chemokines are instrumental in regulating endotoxin-induced transmigration and
      extravascular tissue accumulation of leukocytes. Indeed, these findings
      demonstrate that interference with MIP-2 and KC functions protects against septic
      liver damage and may constitute a potential therapeutic strategy to control
      pathological inflammation in endotoxemia.

PMID- 14673018
TI  - Highly purified lipoteichoic acid activates neutrophil granulocytes and delays
      their spontaneous apoptosis via CD14 and TLR2.
AB  - Lipoteichoic acid (LTA) is a major component of the cell membrane of gram
      positive bacteria. Although LTA has become increasingly recognized as an
      immunomodulator, its effect on polymorphonuclear neutrophil granulocytes (PMN) is
      still not clear. The interaction between LTA and PMN, however, is of particular
      importance, as PMN are the first leukocytes that migrate to the site of infection
      and encounter bacterial pathogens. In the present study, the interaction of
      highly purified human PMN with endotoxin-free LTA from Staphylococcus aureus was
      investigated. After exposure to LTA, neutrophil granulocytes acquired typical
      activated cell morphology. LTA had a marked activating effect on the functions of
      PMN as well. Shedding of CD62L, degranulation, and priming for formyl-Met-Leu-Phe
      mediated oxidative burst were induced in PMN upon exposure to LTA. Moreover, LTA
      treatment induced the release of proinflammatory cytokines such as interleukin-8,
      tumor necrosis factor alpha, and granulocyte-colony stimulating factor by PMN.
      The effects of LTA on PMN were found to be associated with nuclear factor-kappaB
      activation. Of particular interest was that LTA inhibited the spontaneous
      apoptosis and therefore, increased the lifespan of PMN. Experiments using
      blocking antibodies revealed that CD14 and Toll-like receptor 2 (TLR2) but not
      TLR4 play a major role in LTA-mediated effects on PMN. These data clearly show
      that LTA, a component of gram-positive bacteria, directly activates neutrophil
      granulocytes, the primary effector cells in the first line of defense against
      infectious challenge.

PMID- 14673019
TI  - Extracellular and intracellular decoys in the tuning of inflammatory cytokines
      and Toll-like receptors: the new entry TIR8/SIGIRR.
AB  - Following the identification of the interleukin (IL)-1 type II receptor as a
      prototypic decoy receptor, nonsignaling receptors with decoy functions have been
      identified for members of the IL-1/IL-18, tumor necrosis factor, IL-10, and IL-13
      receptor families. Moreover, the silent receptor D6 is a promiscuous decoy and
      scavenger receptor of inflammatory chemokines. The type II IL-1 decoy receptor
      also acts as a dominant-negative molecule. Intracellular pathways of inhibition
      of IL-1 and Toll-like receptor (TLR) signaling have been identified. In
      particular, recent results suggest that the Toll/IL-1 receptor (TIR) family
      member TIR8, also known as single immunoglobulin IL-1-related receptor (SIGIRR),
      is a negative regulator of IL-1 and TLR signaling. Thus, extracellular and
      intracellular decoys tune the activation of members of the IL-1/TLR receptor
      family.

PMID- 14673020
TI  - Functional characterization of the Arabidopsis thaliana orthologue of Tsc13p, the
      enoyl reductase of the yeast microsomal fatty acid elongating system.
AB  - The protein encoded by the Arabidopsis At3g55360 gene was selected as a candidate
      for the enoyl reductase of the microsomal elongase system based on its homology
      to the Tsc13p protein of S. cerevisiae. The studies presented here demonstrate
      that heterologous expression of At3g55360 functionally complements the
      temperature-sensitive phenotype of a yeast tsc13 mutant that is deficient in
      enoyl reductase activity. Furthermore, AtTSC13 is shown to interact physically
      with the Elo2p and Elo3p components of the yeast elongase complex. At3g55360
      apparently encodes the sole enoyl reductase activity associated with microsomal
      fatty acid elongation in Arabidopsis. Consistent with this conclusion, AtTSC13 is
      ubiquitously expressed in Arabidopsis.

PMID- 14673021
TI  - Signalling crosstalk in plants: emerging issues.
AB  - The Oxford English Dictionary defines crosstalk as 'unwanted transfer of signals
      between communication channels'. How does this definition relate to the way in
      which we view the organization and function of signalling pathways? Recent
      advances in the field of plant signalling have challenged the traditional view of
      a signalling transduction cascade as isolated linear pathways. Instead the
      picture emerging of the mechanisms by which plants transduce environmental
      signals is of the interaction between transduction chains. The manner in which
      these interactions occur (and indeed whether the transfer of these signals is
      'unwanted' or beneficial) is currently the topic of intense research.

PMID- 14673022
TI  - Crosstalk between plant responses to pathogens and herbivores: a view from the
      outside in.
AB  - Plants encounter numerous pests and pathogens in the natural environment. An
      appropriate response to attack by such organisms can lead to tolerance or
      resistance mechanisms that enable the plant to survive. Many studies concentrate
      on the signalling pathways that enable plants to recognize and respond to attack,
      and measure the downstream effect in either biochemical or molecular terms. At
      the whole plant level, ecologists examine the fitness costs of attack not only
      for the plant but also over a range of trophic levels. The links between these
      differing levels of study are beginning to be addressed by the adoption of
      molecular approaches in more ecologically relevant settings. This review will
      describe the different approaches used by ecologists and cell biologists in this
      field and will try to address the question of how we can explore the response to,
      and consequences, of attack by multiple enemies.

PMID- 14673023
TI  - Characterization in maize of ZmTIP2-3, a root-specific tonoplast intrinsic
      protein exhibiting aquaporin activity.
AB  - The characterization of the tonoplast intrinsic protein ZmTIP2-3 cDNA isolated
      from maize roots is reported. ZmTIP2-3 belongs to the TIP2 group according to the
      present nomenclature. The aquaporin function of ZmTIP2-3 protein was demonstrated
      using expression in X. laevis oocytes. Northern blot analyses revealed that
      ZmTIP2-3 was specifically expressed in roots. Salt and water stresses induced the
      accumulation of ZmTIP2-3 transcripts. By contrast, no effect of ABA was observed.
      An oscillation of ZmTIP2-3 transcript amount during the day-night cycle was
      observed with some typical features of genes regulated by a circadian mechanism.

PMID- 14673024
TI  - Sugar and phytohormone response pathways: navigating a signalling network.
AB  - Many plant developmental, physiological and metabolic processes are regulated, at
      least in part, by nutrient availability. In particular, alterations in the
      availability of soluble sugars, such as glucose and sucrose, help regulate a
      diverse array of processes. Multiple lines of evidence indicate that many of
      these processes are also regulated in response to other signalling molecules,
      such as phytohormones. This review draws examples from a variety of plant
      systems, including bean, Arabidopsis, potato, and cereals. Five of the most
      interesting and best developed examples of processes regulated via 'interactions'
      or 'crosstalk' between sugars and phytohormones are described, including
      embryogenesis, seed germination, early seedling development, tuberization, and
      the regulation of alpha-amylase activity. The types of mechanisms by which
      different response pathways are known or postulated to interact are also
      described. These mechanisms include regulation of the metabolism and/or transport
      of a signalling molecule by a different response pathway. For example, sugars
      have been postulated to help regulate the synthesis, conjugation and/or transport
      of phytohormones, such as gibberellins and abscisic acid. Conversely,
      phytohormones, such as abscisic acid, gibberellins and cytokinins have been shown
      to help regulate sugar metabolism and/or transport. Similarly, sugars have been
      shown to regulate the expression of components of phytohormone-response pathways
      and phytohormones regulate the expression of some genes encoding possible
      components of sugar-response pathways. Examples of proteins and second messengers
      that appear to act in multiple response pathways are also described.

PMID- 14673025
TI  - Isolation and characterization of a Pti1 homologue from soybean.
AB  - A full-length gene GmPti1 was identified from soybean in an EST sequencing
      project by its homology to tomato Pti1. It encoded a protein of 366 amino acids.
      RT-PCR analysis showed that the GmPti1 expression was induced by salicylic acid
      and wounding. The deduced amino acid sequence had a Ser/Thr/Tyr kinase domain.
      GmPti1 protein was expressed in E. coli as an MBP fusion, purified by amylose
      resin and examined for its autophosphorylation ability. The phosphorylation assay
      in vitro showed that GmPti1 had kinase activity in the presence of Mn2+. These
      results demonstrated that GmPti1 represented a new Pti1-like gene, unlike the two
      published genes sPti1a and sPti1b, which encoding proteins had no
      autophosphorylation ability.

PMID- 14673026
TI  - ABA, hydrogen peroxide and nitric oxide signalling in stomatal guard cells.
AB  - Increased synthesis and redistribution of the phytohormone abscisic acid (ABA) in
      response to water deficit stress initiates an intricate network of signalling
      pathways in guard cells leading to stomatal closure. Despite the large number of
      ABA signalling intermediates that are known in guard cells, new discoveries are
      still being made. Recently, the reactive oxygen species hydrogen peroxide (H2O2)
      and the reactive nitrogen species nitric oxide (NO) have been identified as key
      molecules regulating ABA-induced stomatal closure in various species. As with
      many other physiological responses in which H2O2 and NO are involved, stomatal
      closure in response to ABA also appears to require the tandem synthesis and
      action of both these signalling molecules. Recent pharmacological and genetic
      data have identified NADPH oxidase as a source of H2O2, whilst nitrate reductase
      has been identified as a source of NO in Arabidopsis guard cells. Some signalling
      components positioned downstream of H2O2 and NO are calcium, protein kinases and
      cyclic GMP. However, the exact interaction between the various signalling
      components in response to H2O2 and NO in guard cells remains to be established.

PMID- 14673027
TI  - Hormone signalling from a developmental context.
AB  - The influence of hormones on plant growth and development has been clearly
      documented over the past 50 years. Now, with molecular genetics, the genes that
      convert changes in hormone levels into a cellular response are beginning to be
      identified. However, recent studies have demonstrated that the developmental
      context in which the hormones act plays a large influence on their synthesis and
      action. In this review, examples are given where known hormone response genes
      have been shown to have broader developmental roles as well as examples where
      genes that regulate developmental decisions, such as differentiation and fate,
      also influence hormone metabolism. The early conclusion of these studies is that
      an understanding of hormone signal transduction cannot be achieved in the absence
      of a developmental framework.

PMID- 14673028
TI  - Maintenance of shoot growth by endogenous ABA: genetic assessment of the
      involvement of ethylene suppression.
AB  - Previous work demonstrated that normal levels of endogenous abscisic acid (ABA)
      are required to maintain shoot growth in well-watered tomato plants independently
      of effects of hormone status on plant water balance. The results suggested that
      the impairment of shoot growth in ABA-deficient mutants is at least partly
      attributable to increased ethylene production. To assess the extent to which ABA
      maintains shoot growth by ethylene suppression, the growth of ABA-deficient (aba2
      1) and ethylene-insensitive (etr1-1) single- and double-mutants of Arabidopsis
      was examined. To ensure that the results were independent of effects of hormone
      status on plant water balance, differential relative humidity regimes were used
      to achieve similar leaf water potentials in all genotypes and treatments. In aba2
      1, shoot growth was substantially inhibited and ethylene evolution was doubled
      compared with the wild type, consistent with the results for tomato. In the aba2
      1 etr1-1 double mutant, in which ABA was equally as deficient as in aba2-1 and
      shoot growth was shown to be insensitive to ethylene, shoot growth was
      substantially, although incompletely, restored relative to etr1-1. Treatment with
      ABA resulted in the complete recovery of shoot growth in aba2-1 relative to the
      wild type, and also significantly increased the growth of aba2-1 etr1-1 such that
      total leaf area and shoot fresh weight were not significantly lower than in etr1
      1. In addition, ABA treatment of aba2-1 etr1-1 restored the wider leaf morphology
      phenotype exhibited by etr1-1. The results demonstrate that normal levels of
      endogenous ABA maintain shoot development, particularly leaf expansion, in well
      watered Arabidopsis plants, partly by suppressing ethylene synthesis and partly
      by another mechanism that is independent of ethylene.

PMID- 14673029
TI  - The effects of manipulating phospholipase C on guard cell ABA-signalling.
AB  - Studies using stably transformed tobacco plants containing very low levels of PI
      PLC in their guard cells show that this enzyme plays a role in the events
      associated with the inhibition of stomatal opening by ABA, but not in the
      cellular reactions that are responsible for ABA-induced stomatal closure.
      However, Commelina communis guard cells microinjected with the InsP3 antagonist,
      heparin, fail to close on addition of ABA. There are three possible explanations
      for this apparent data mismatch. The differences may be indicative of species
      specific signalling pathways, the presence of a PI-PLC isoform(s) that is not
      down-regulated in these transgenic lines and/or they may reflect differences
      between short-term (acute) administration of an inhibitor and long-term (chronic)
      effects of gene manipulation. It is possible that the guard cell is a robust
      signalling system that is able to adapt or compensate for the chronic loss of PI
      PLC, but which is unable to adjust quickly to acute loss of this component. It
      would be interesting to investigate this possibility further using either
      transient manipulation of gene expression or through the use of an inducible
      promoter.

PMID- 14673030
TI  - Light signals, phytochromes and cross-talk with other environmental cues.
AB  - Plants have evolved highly complex sensory mechanisms to monitor their
      surroundings and adapt their growth and development to the prevailing
      environmental conditions. The integration of information from multiple
      environmental cues enables the co-ordination of development with favourable
      seasonal conditions and, ultimately, determines plant form. Light signals,
      perceived via the phytochrome, cryptochrome and phototropin photoreceptor
      families, are especially important environmental signals. Redundancy of function
      among phytochromes and their interaction with blue light photoreceptors enhance
      sensitivity to light signals, facilitating the accurate detection of, and
      response to, environmental fluctuations. In this review, current understanding of
      Arabidopsis phytochrome functions will be summarized, in particular, the
      interactions among the phytochromes and the integration of light signals with
      directional and temperature sensing mechanisms.

PMID- 14673031
TI  - Signals for local and systemic responses of plants to pathogen attack.
AB  - Activation of plant defences following recognition of pathogen attack involves
      complex reiterative signal networks with extensive signal amplification and cross
      talk. The results of two approaches that have been taken to analyse signalling in
      plant-microbe interactions are discussed here. Activation tagging with T-DNA
      harbouring multiple 35S enhancer elements was employed as a gain-of-function
      approach to dissect signalling related to bacterial pathogen resistance in
      Arabidopsis thaliana. From a screen of approximately 5000 activation tagged
      lines, one line was identified as harbouring a T-DNA leading to over-expression
      of an apoplastic aspartic protease (CDR-1), that resulted in resistance to
      normally virulent Pseudomonas syringae. The second approach was to screen for
      loss-of-function mutants in T-DNA tagged populations. From a screen of 11 000
      lines, one line, defective in induced resistance-1 (dir-1) lost resistance to
      normally avirulent P. syringae. Models for action of the products of the CDR-1
      and DIR-1 genes suggest involvement of peptide and lipid signals in systemic
      disease resistance responses in A. thaliana.

PMID- 14673032
TI  - BRing it on: new insights into the mechanism of brassinosteroid action.
AB  - Several recent breakthroughs have filled in key details of the brassinosteroid
      (BR) response. Identification of BAK1, a BRI1 interacting protein, the negative
      regulator BIN2, as well as direct targets of BIN2, BZR1 and BES1, provide a link
      between BR perception at the cell surface and regulation of gene expression in
      the nucleus. Global expression studies further defined the downstream events in
      this pathway, confirming the role of several factors acting in negative feedback
      regulation on BR levels. New links to the plant hormone, auxin, were also
      uncovered.

PMID- 14673033
TI  - From signal to cell polarity: mitogen-activated protein kinases as sensors and
      effectors of cytoskeleton dynamicity.
AB  - Mitogen-activated protein kinases (MAPKs) are ubiquitous phosphorylation enzymes
      involved in signal transduction, gene expression and activation of diverse
      cytoskeletal proteins. MAPKs participate in the regulation of a broad range of
      crucial cellular processes including cell survival, division, polarization,
      stress responses, and metabolism. Phosphorylation of cytoskeletal proteins
      usually results in the rearrangement of cytoskeletal arrays leading to
      morphological changes and cell polarization. On the other hand, some cytoskeletal
      motor proteins, such as kinesins, could activate MAPK members and participate in
      signal delivery to the proper cellular destination (e.g. during cell division).
      Moreover, changes in the integrity of cytoskeletal elements have direct impacts
      on MAPK activity. Recent evidence suggests that there is bi-directional
      signalling between MAPK cascades and cytoskeleton. The focus here is on this
      cross-talk between MAPK signalling and the cytoskeleton in various eukaryotic
      systems including yeast, plants, and mammals and a role is proposed for MAPKs as
      sensors monitoring the cytoskeleton-dependent balance of forces within the cell.

PMID- 14673034
TI  - RIKEN Arabidopsis full-length (RAFL) cDNA and its applications for expression
      profiling under abiotic stress conditions.
AB  - Full-length cDNAs are essential for the correct annotation of genomic sequences
      and for the functional analysis of genes and their products. 155,144 RIKEN
      Arabidopsis full-length (RAFL) cDNA clones were isolated. The 3'-end expressed
      sequence tags (ESTs) of all 155,144 RAFL cDNAs were clustered into 14,668 non
      redundant cDNA groups, about 60% of predicted genes. The sequence database of the
      RAFL cDNAs is useful for promoter analysis and the correct annotation of
      predicted transcription units and gene products. Recently, cDNA microarray
      analysis has been developed for quantitative analysis of global and simultaneous
      analysis of expression profiles. RAFL cDNA microarrays were prepared, containing
      independent full-length cDNA groups for analysing the expression profiles of
      genes under various stress- and hormone-treatment conditions and in various
      mutants and transgenic plants. In this review, recent progress on transcriptome
      analysis using the RAFL cDNA microarray is highlighted.

PMID- 14673035
TI  - Molecular genetic perspectives on cross-talk and specificity in abiotic stress
      signalling in plants.
AB  - The perception of abiotic stresses and signal transduction to switch on adaptive
      responses are critical steps in determining the survival and reproduction of
      plants exposed to adverse environments. Plants have stress-specific adaptive
      responses as well as responses which protect the plants from more than one
      environmental stress. There are multiple stress perception and signalling
      pathways, some of which are specific, but others may cross-talk at various steps.
      Recently, progress has been made in identifying components of signalling pathways
      involved in salt, drought and cold stresses. Genetic analysis has defined the
      Salt-Overly-Sensitive (SOS) pathway, in which a salt stress-induced calcium
      signal is probably sensed by the calcium-binding protein SOS3 which then
      activates the protein kinase SOS2. The SOS3-SOS2 kinase complex regulates the
      expression and activity of ion transporters such as SOS1 to re-establish cellular
      ionic homeostasis under salinity. The ICE1 (Inducer of CBF Expression 1)-CBF (C
      Repeat Binding Protein) pathway is critical for the regulation of the cold
      responsive transcriptome and acquired freezing tolerance, although at present the
      signalling events that activate the ICE1 transcription factor during cold stress
      are not known. Both ABA-dependent and -independent signalling pathways appear to
      be involved in osmotic stress tolerance. Components of mitogen-activated protein
      kinase (MAPK) cascades may act as converging points of multiple abiotic as well
      as biotic stress signalling pathways. Forward and reverse genetic analysis in
      combination with expression profiling will continue to uncover many signalling
      components, and biochemical characterization of the signalling complexes will be
      required to determine specificity and cross-talk in abiotic stress signalling
      pathways.

PMID- 14673036
TI  - 6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and
      mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged
      maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive
      consolidation by sequential HAM in adult patients at all ages with de novo acute
      myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group.
AB  - PURPOSE: To examine the efficacy of prolonged maintenance chemotherapy versus
      intensified consolidation therapy for patients with acute myeloid leukemia (AML).
      MATERIALS AND METHODS: Eight hundred thirty-two patients (median age, 54 years;
      range, 16 to 82 years) with de novo AML were randomly assigned to receive 6
      thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone
      (HAM; cytarabine 3 g/m2 [age < 60 years] or 1 g/m2 [age > or = 60 years] x 6)
      induction, TAD consolidation, and monthly modified TAD maintenance for 3 years,
      or TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S
      HAM) with cytarabine 1 g/m2 (age < 60 years) or 0.5 g/m2 (age > or = 60 years) x
      8 instead of maintenance. RESULTS: A total of 69.2% patients went into complete
      remission (CR). Median relapse-free survival (RFS) was 19 months for patients on
      the maintenance arm, with 31.4% of patients relapse-free at 5 years, versus 12
      months for patients on the S-HAM arm, with 24.7% of patients relapse-free at 5
      years (P =.0118). RFS from maintenance was superior in patients with poor risk by
      unfavorable karyotype, age > or = 60 years, lactate dehydrogenase level greater
      than 700 U/L, or day 16 bone marrow blasts greater than 40% (P =.0061) but not in
      patients with good risk by complete absence of any poor risk factors. Although a
      survival benefit in the CR patients is not significant (P =.085), more surviving
      patients in the maintenance than in the S-HAM arm remain in first CR (P =.026).
      CONCLUSION: We conclude that TAD-HAM-TAD-maintenance first-line treatment has a
      higher curative potential than TAD-HAM-TAD-S-HAM and improves prognosis even
      among patients with poor prognosis.

PMID- 14673037
TI  - TP53, BRCA1, and BRCA2 tumor suppressor genes are not commonly mutated in
      survivors of Hodgkin's disease with second primary neoplasms.
AB  - PURPOSE: Despite recognition that second malignant neoplasms (SMNs) contribute
      significantly to mortality after the successful treatment of Hodgkin's disease
      (HD), little is known about the molecular events leading to secondary tumors.
      Factors contributing to second cancer risk include the carcinogenic effects of
      ionizing radiation and chemotherapy, in combination with possible host
      susceptibility. To clarify whether host genetic factors contribute to secondary
      tumorigenesis, we performed mutational analyses of the TP53, BRCA1, and BRCA2
      tumor suppressor genes in a cohort of 44 HD patients developing one or more SMN.
      PATIENTS AND METHODS: Family cancer histories and constitutional DNA samples were
      obtained from 44 HD patients with SMNs identified. Using DNA-based sequencing, we
      evaluated the TP53 gene in all 44 patients. Nineteen female patients developing
      one or more secondary breast cancer were also analyzed for mutations in the BRCA1
      and BRCA2 breast cancer-susceptibility genes. RESULTS: Nineteen patients (43%)
      had more than one SMN, and 12 patients (27%) had a positive family history of
      cancer. One of 44 patients tested for TP53 harbored a novel homozygous germline
      abnormality. One of 19 patients tested for BRCA2 carried a previously described
      heterozygous inactivating mutation. We identified no germline BRCA1 mutations.
      CONCLUSION: Despite features suggestive of genetic predisposition, the TP53,
      BRCA1, and BRCA2 genes were not frequently mutated in this cohort of HD patients
      developing SMNs. Larger studies of these genes or investigations of other genes
      involved in cellular DNA damage response pathways may identify host genetic
      factors that contribute to secondary tumorigenesis.

PMID- 14673038
TI  - Adjuvant endocrine therapy compared with no systemic therapy for elderly women
      with early breast cancer: 21-year results of International Breast Cancer Study
      Group Trial IV.
AB  - PURPOSE: Increasing numbers of older women are affected by early breast cancer,
      because of prolonged life expectancy and the increasing incidence of breast
      cancer with age. The role of adjuvant therapy for this population is still a
      matter of debate. We reviewed the long-term outcome of a mature trial comparing
      endocrine treatment versus no adjuvant therapy in older women with node-positive
      breast cancer. PATIENTS AND METHODS: From 1978 to 1981, 349 women 66 to 80 years
      of age with pathologically involved lymph nodes after total mastectomy and
      axillary clearance were randomly assigned to receive 12 months of adjuvant
      tamoxifen plus low-dose prednisone (p+T) or no adjuvant therapy. Three hundred
      twenty patients were eligible. RESULTS: At 21 years' median follow-up, 1 year of
      p+T significantly prolonged disease-free survival (DFS; P =.003) and overall
      survival (P =.05; 15-year DFS, 10% +/- 3% v 19% +/- 3%; hazard ratio, 0.71; 95%
      CI, 0.58 to 0.86). When comparing competing causes of failure (breast cancer
      recurrence and deaths before breast cancer recurrence), p+T was far superior in
      controlling breast cancer recurrence (P =.0003), but the improvement was seen
      mainly in soft tissue sites. Conversely, patients in the p+T group were more
      likely to die before a breast cancer recurrence (P =.03). CONCLUSION: This trial
      demonstrates that significant treatment benefits continue to be observed in older
      patients treated for 1 year with p+T. Despite issues relating to competing causes
      of failure, older breast cancer patients can benefit from treatment and should be
      considered for trials of adjuvant systemic therapy.

PMID- 14673039
TI  - Incidence and predictors of low dose-intensity in adjuvant breast cancer
      chemotherapy: a nationwide study of community practices.
AB  - PURPOSE: This retrospective study was undertaken to assess practice patterns in
      adjuvant chemotherapy for early-stage breast cancer (ESBC) and to define the
      incidence and predictive factors of reduced relative dose-intensity (RDI).
      PATIENTS AND METHODS: A nationwide survey of 1,243 community oncology practices
      was conducted, with data extracted from records of 20,799 ESBC patients treated
      with adjuvant chemotherapy. Assessments included demographic and clinical
      characteristics, chemotherapy dose modifications, incidence of febrile
      neutropenia, and patterns of use of colony-stimulating factor (CSF). Dose
      intensity was compared with published reference standard regimens. RESULTS: Dose
      reductions > or =15% occurred in 36.5% of patients, and there were treatment
      delays > or =7 days in 24.9% of patients, resulting in 55.5% of patients
      receiving RDI less than 85%. Nearly two thirds of patients received RDI less than
      85% when adjusted for differences in regimen dose-intensity. Multivariate
      analysis identified several independent predictors for reduced RDI, including
      increased age; chemotherapy with cyclophosphamide, methotrexate, and
      fluorouracil, or cyclophosphamide, doxorubicin, and fluorouracil; a 28-day
      schedule; body-surface area greater than 2 m2; and no primary CSF prophylaxis.
      CSF was often initiated late in the chemotherapy cycle. CONCLUSION: Patients with
      ESBC are at substantial risk for reduced RDI when treated with adjuvant
      chemotherapy. Patients at greatest risk include older patients, overweight
      patients, and those receiving three-drug combinations or 28-day schedules.
      Predictive models based on such risk factors should enable the selective
      application of supportive measures in an effort to deliver full dose-intensity
      chemotherapy.

PMID- 14673040
TI  - Consultation with a medical oncologist before surgery and type of surgery among
      elderly women with early-stage breast cancer.
AB  - PURPOSE: Prior studies have documented variation in breast cancer treatment and
      care that does not follow guideline recommendations, particularly for elderly
      women. We assessed whether consultation with a medical oncologist before surgery
      was associated with use of definitive surgery, axillary node dissection, and type
      of surgery. METHODS: We conducted a retrospective cohort study of a population
      based sample of 9,630 women aged > or = 66 years diagnosed with breast cancer
      during 1995 to 1996. We measured the adjusted proportion visiting a medical
      oncologist before surgery, identified factors associated with such visits, and
      assessed the association between visits with a medical oncologist and use of
      definitive surgery (mastectomy or breast-conserving surgery with radiation v
      breast-conserving surgery without radiation); axillary dissection; and breast
      conserving surgery versus mastectomy among women undergoing definitive surgery.
      RESULTS: Nineteen percent of women visited a medical oncologist before surgery;
      these women were younger, more often had larger or more poorly differentiated
      cancers, had more comorbid illnesses, and were treated more often at a teaching
      hospital (all P <.05). Women who saw a medical oncologist before surgery were
      more likely than others to undergo definitive surgery (adjusted odds ratio [OR],
      1.28; 95% CI, 1.05 to 1.56) and axillary dissection (adjusted OR, 1.44; 95% CI,
      1.19 to 1.73), but less likely to undergo breast-conserving surgery among women
      undergoing definitive surgery (OR, 0.84; 95% CI, 0.75 to 0.95). CONCLUSION:
      Elderly women who consulted with a medical oncologist before surgery were more
      likely to receive guideline-recommended care. Additional research is needed allow
      a better understanding of the quality and content of discussions that elderly
      women have with various providers about breast-conserving surgery and mastectomy.

PMID- 14673041
TI  - Is surgery necessary after complete clinical remission following neoadjuvant
      chemotherapy for early breast cancer?
AB  - PURPOSE: This retrospective analysis aimed to identify whether breast cancer
      patients receiving radiotherapy alone following a complete clinical remission
      (cCR) to neoadjuvant chemotherapy had a worse outcome than those treated with
      surgery. PATIENTS AND METHODS: One hundred thirty-six patients who had achieved a
      cCR to neoadjuvant chemotherapy for early breast cancer were identified from a
      prospectively maintained database of 453 patients. Of these, 67 patients had
      undergone surgery as their primary locoregional therapy, and 69 patients had
      radiotherapy alone. Outcome was assessed in relation to local recurrence-free
      survival, disease-free survival, and overall survival. RESULTS: Median follow-up
      was 63 months in the surgery group and 87 months in the no surgery group.
      Prognostic characteristics were well balanced between the two groups. For surgery
      and no surgery, respectively, there were no significant differences in disease
      free survival or overall survival (5-year, 74% v 76%; 10-year, 60% v 70%, P =.9)
      between the two groups. There was a nonsignificant trend toward increased
      locoregional-only recurrence for the no surgery group (21% v 10% at 5 years; P
      =.09), but no long-term failures of local control. Patients in the no surgery
      group who also achieved an ultrasound complete remission had a 5-year local
      recurrence rate of only 8%. CONCLUSION: In patients achieving a cCR to
      neoadjuvant chemotherapy, radiotherapy alone achieve survival rates as good as
      with surgery, but with higher local recurrence rates. Ultrasound may identify a
      low recurrence rate subgroup for assessing no surgery in a prospective trial.

PMID- 14673042
TI  - Analysis of factors associated with outcome in patients with malignant peritoneal
      mesothelioma undergoing surgical debulking and intraperitoneal chemotherapy.
AB  - PURPOSE: Malignant mesothelioma (MM) arising in the peritoneal cavity is a rare
      neoplasm characterized by peritoneal progression and for which there are limited
      therapeutic options. We evaluated the peritoneal progression-free and overall
      survival (PFS and OS, respectively) for patients with peritoneal MM after
      surgical resection and regional chemotherapy. PATIENTS AND METHODS: Forty-nine
      patients (28 males, 21 females; median age, 47 years; range, 16 to 76 years) with
      MM underwent laparotomy, tumor resection, continuous hyperthermic peritoneal
      perfusion with cisplatin (median dose 250 mg/m2), and a single postoperative
      intraperitoneal dwell of fluorouracil and paclitaxel (n = 35) on protocols
      approved by the Institutional Review Board. Standard techniques for actuarial
      analyses of potential prognostic variables (Kaplan-Meier method with two-tailed
      log-rank test and Cox proportional hazards model) were performed. RESULTS: At a
      median potential follow-up of 28.3 months, median actuarial PFS is 17 months and
      actuarial OS is 92 months. Factors associated with improved PFS and OS by the Cox
      proportional hazards model were a history of previous debulking surgery, absence
      of deep tissue invasion, minimal residual disease after surgical resection (OS
      only), and age younger than 60 years (OS only). CONCLUSION: Surgical resection
      and regional chemotherapy for MM results in durable PFS and OS. Favorable outcome
      is associated with age, tumor biology (selection of patients with a history of
      previous debulking), lack of invasive tumor growth, and minimal residual disease
      after tumor resection.

PMID- 14673043
TI  - Pretreatment nomogram that predicts 5-year probability of metastasis following
      three-dimensional conformal radiation therapy for localized prostate cancer.
AB  - PURPOSE: There are several nomograms for the patient considering radiation
      therapy for clinically localized prostate cancer. Because of the questionable
      clinical implications of prostate-specific antigen (PSA) recurrence, its use as
      an end point has been criticized in several of these nomograms. The goal of this
      study was to create and to externally validate a nomogram for predicting the
      probability that a patient will develop metastasis within 5 years after three
      dimensional conformal radiation therapy (CRT). PATIENTS AND METHODS: We conducted
      a retrospective, nonrandomized analysis of 1,677 patients treated with three
      dimensional CRT at Memorial Sloan-Kettering Cancer Center (MSKCC) from 1988 to
      2000. Clinical parameters examined were pretreatment PSA level, clinical stage,
      and biopsy Gleason sum. Patients were followed until their deaths, and the time
      at which they developed metastasis was noted. A nomogram for predicting the 5
      year probability of developing metastasis was constructed from the MSKCC cohort
      and validated using the Cleveland Clinic series of 1,626 patients. RESULTS: After
      three-dimensional CRT, 159 patients developed metastasis. At 5 years, 11% of
      patients experienced metastasis by cumulative incidence analysis (95% CI, 9% to
      13%). A nomogram constructed from the data gathered from these men showed an
      excellent ability to discriminate among patients in an external validation data
      set, as shown by a concordance index of 0.81. CONCLUSION: A nomogram with
      reasonable accuracy and discrimination has been constructed and validated using
      an external data set to predict the probability that a patient will experience
      metastasis within 5 years after three-dimensional CRT.

PMID- 14673044
TI  - Progression-free survival in children with optic pathway tumors: dependence on
      age and the quality of the response to chemotherapy--results of the first French
      prospective study for the French Society of Pediatric Oncology.
AB  - PURPOSE: To evaluate a strategy aimed at avoiding radiotherapy during first-line
      treatment of children with progressive optic pathway tumors (OPT), by exclusively
      administering multiagent chemotherapy during 16 months. PATIENTS AND METHODS:
      Between 1990 and 1998, 85 children with progressive OPT were enrolled onto this
      multicenter nationwide trial. Chemotherapy alternating procarbazine plus
      carboplatin, etoposide plus cisplatin, and vincristine plus cyclophosphamide was
      given every 3 weeks. At the time of relapse or progression, second-line
      chemotherapy was authorized before recourse to radiotherapy. RESULTS: Objective
      response rate (partial response [PR] + complete response [CR]) to chemotherapy
      was 42%. Five-year progression-free survival (PFS) and overall survival rates
      were 34% and 89%, respectively. The 5-year radiotherapy-free survival rate was
      61%. In the multivariate analysis of the 85 patients that entered onto the study,
      factors associated with the risk of disease progression were age younger than 1
      year at diagnosis (P =.047) and absence of neurofibromatosis type 1 (P =.035). In
      the multivariate analysis of the 74 patients that remained on study after the
      first cycle of chemotherapy, factors associated with the risk of disease
      progression were age younger than 1 year at diagnosis (P =.0053) and no objective
      response to chemotherapy (P =.0029). Three-year PFS was 44% in infants < or = 1
      year versus 66% in children older than 1 year. Three-year PFS was 53% in the
      absence of an objective response to chemotherapy versus 68% after a PR or CR.
      CONCLUSION: A significant proportion of children with OPT can avoid radiotherapy
      after prolonged chemotherapy. Deferring irradiation with chemotherapy protocols
      did not compromise overall survival of the entire population or visual function.

PMID- 14673045
TI  - Characteristics and outcomes of children with the Wilms tumor-Aniridia syndrome:
      a report from the National Wilms Tumor Study Group.
AB  - PURPOSE: Children with the rare Wilms tumor (WT)-aniridia (WAGR) syndrome have
      not had systematic evaluation of their clinical and pathologic features. We
      compared demographics, disease characteristics, and treatment outcomes in a large
      cohort of WT patients who did or did not have the WAGR syndrome. PATIENTS AND
      METHODS: Clinical and pathology records were reviewed for 8,533 patients enrolled
      between 1969 and 2002 by the National Wilms Tumor Study Group. RESULTS: Sixty
      four patients (0.75%) had the WAGR syndrome. For WAGR and non-WAGR patients,
      respectively, the average birth weights (2.94 and 3.45 kg), median ages at
      diagnosis (22 and 39 months), and the percentages with bilateral disease (17% and
      6%), metastatic disease (2% and 13%), favorable histology (FH) tumors (100% and
      92%), and intralobar nephrogenic rests (ILNR; 77% and 22%) all differed. Survival
      estimates for WAGR and non-WAGR patients were 95% +/- 3% and 92% +/- 0.3% at 4
      years but 48% +/- 17% and 86% +/- 1.0%, respectively, at 27 years from diagnosis.
      Five late deaths in WAGR patients were from end-stage renal disease (ESRD).
      CONCLUSION: The excess of bilateral disease, ILNR-associated FH tumors of mixed
      cell type, and early ages at diagnosis in WAGR patients all fit the known
      phenotypic spectrum of constitutional deletion of chromosome 11p13. Despite a
      favorable response of their WT to treatment, WAGR patients have a high risk of
      ESRD as they approach adulthood. The renal pathology associated with this
      apparent late manifestation of WT1 deletion, and the explanation for the
      abnormally low birth weights in patients with del 11p13, have yet to be
      determined.

PMID- 14673046
TI  - Topoisomerase-II alpha is upregulated in malignant peripheral nerve sheath tumors
      and associated with clinical outcome.
AB  - PURPOSE: To identify target genes of clinical significance for patients with
      malignant peripheral-nerve sheath tumor (MPNST), an aggressive cancer for which
      no consensus therapy exists. MATERIALS AND METHODS: Biopsies and clinical data
      from 51 patients with MPNST were included in this study. Based on our previous
      research implicating chromosome arm 17q amplification in MPNST, we performed gene
      expression analyses of 14 MPNSTs using chromosome 17-specific cDNA microarrays.
      Copy numbers of selected gene probes and centromere probes were then determined
      by interphase fluorescence in situ hybridization in 16 MPNSTs. Finally, we
      generated a tissue microarray containing 79 samples from 44 MPNSTs, on which in
      situ protein expressions of candidate genes were examined and related to clinical
      end points. RESULTS: Among several deregulated genes found by cDNA microarray
      analyses, topoisomerase II alpha (TOP2A) was the most overexpressed gene in
      MPNSTs compared with benign neurofibromas. Excess copies of the TOP2A were also
      seen at the DNA level in 10 of 16 cases, and high expression of the TOP2A protein
      was seen in 83% of the tumors on the tissue microarray. The TOP2A-expressing
      tumors were associated with poor cancer-specific survival and presence of
      metastases. CONCLUSION: We have identified TOP2A as a target gene in MPNST, using
      a focused gene expression profiling followed by a DNA copy number evaluation and
      clinical validation of the encoded protein using a tissue microarray. This study
      is the first to suggest that TOP2A expression may be a predictive factor for
      adverse outcome in MPNST.

PMID- 14673047
TI  - Surgery plus chemotherapy compared with surgery alone for localized squamous cell
      carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study-
      JCOG9204.
AB  - PURPOSE: We performed a multicenter randomized controlled trial to determine
      whether postoperative adjuvant chemotherapy improves outcome in patients with
      esophageal squamous cell carcinoma undergoing radical surgery. PATIENTS AND
      METHODS: Patients undergoing transthoracic esophagectomy with lymphadenectomy
      between July 1992 and January 1997 at 17 institutions were randomly assigned to
      receive surgery alone or surgery plus chemotherapy including two courses of
      cisplatin (80 mg/m2 of body-surface area x 1 day) and fluorouracil (800 mg/m2 x 5
      days) within 2 months after surgery. Adaptive stratification factors were
      institution and lymph node status (pN0 versus pN1). The primary end point was
      disease-free survival. RESULTS: Of the 242 patients, 122 were assigned to surgery
      alone, and 120 to surgery plus chemotherapy. In the surgery plus chemotherapy
      group, 91 patients (75%) received both full courses of chemotherapy; grade 3 or 4
      hematologic or nonhematologic toxicities were limited. The 5-year disease-free
      survival rate was 45% with surgery alone, and 55% with surgery plus chemotherapy
      (one-sided log-rank, P =.037). The 5-year overall survival rate was 52% and 61%,
      respectively (P =.13). Risk reduction by postoperative chemotherapy was
      remarkable in the subgroup with lymph node metastasis. CONCLUSION: Postoperative
      adjuvant chemotherapy with cisplatin and fluorouracil is better able to prevent
      relapse in patients with esophageal cancer than surgery alone.

PMID- 14673048
TI  - Interaction of splenectomy and perioperative blood transfusions on prognosis of
      patients with proximal gastric and gastroesophageal junction cancer.
AB  - PURPOSE: To assess the interaction of splenectomy and perioperative allogeneic
      blood transfusions on the prognosis of patients undergoing a potentially curative
      resection of proximal gastric and gastroesophageal junction (GEJ) cancer, because
      reports from the transplantation literature demonstrated that the
      immunosuppressive effects of transfusions are dependent on the presence of an
      intact spleen. PATIENTS AND METHODS: Between July 1, 1985, and July 30, 2001, 240
      patients underwent complete resection (R0) of a proximal gastric or GEJ cancer
      (Siewert type II or III). Clinical and pathologic factors were collected in a
      prospective database. The survival data were modeled using the method of Kaplan
      and Meier and analyzed by the log-rank test and Cox regression. RESULTS: The
      median follow-up of the patients was 25 months (40 months for survivors). The
      median relapse-free survival was 30 months, and the median disease-specific
      survival was 45 months. Univariate analysis suggested an interaction of
      splenectomy and perioperative transfusion in their effect on relapse-free
      survival. Patients who received a perioperative transfusion but did not undergo
      splenectomy demonstrated the worst prognosis on multivariate analysis independent
      of other prognostic factors. In patients who underwent splenectomy, perioperative
      transfusion had no effect on relapse-free survival on multivariate analysis.
      CONCLUSION: Our study suggests an interaction of blood transfusion and
      splenectomy in their effect on survival paralleling the findings in the
      transplantation literature. The adverse effect of allogeneic blood transfusion on
      prognosis in patients with gastric cancer seems to be associated with the
      presence of an intact spleen and is abrogated by its absence.

PMID- 14673049
TI  - Prediction of response to preoperative chemotherapy in gastric carcinoma by
      metabolic imaging: results of a prospective trial.
AB  - PURPOSE: We prospectively evaluated the predictive value of therapy-induced
      reduction of tumor glucose use for subsequent response and patient survival in
      patients with gastric cancer treated by preoperative chemotherapy. PATIENTS AND
      METHODS: Forty-four consecutive patients with locally advanced gastric carcinomas
      were studied by positron emission tomography with the glucose analog fluorine-18
      fluorodeoxyglucose (FDG-PET) at baseline and 14 days after initiation of
      cisplatin-based polychemotherapy. On the basis of a previous study, a reduction
      of tumor FDG uptake by more than 35% was used as a criterion for a metabolic
      response. The metabolic response in FDG-PET was correlated with histopathologic
      response after completion of therapy (< 10% viable tumor cells in the resected
      specimen) and patient survival. RESULTS: Thirty-five (80%) of the 44 tumors were
      visualized with sufficient contrast for quantitative analysis (two of 19
      intestinal and seven of 25 nonintestinal tumors showed only low FDG uptake). In
      the 35 assessable patients, PET imaging after 14 days of therapy correctly
      predicted histopathologic response after 3 months of therapy in 10 (77%) of 13
      responders and 19 (86%) of 22 nonresponders. Median overall survival for patients
      with a metabolic response has not been reached (2-year survival rate, 90%); for
      patients without a metabolic response, median survival was only 18.9 months (2
      year survival rate, 25%; P =.002) CONCLUSION: This study prospectively
      demonstrates that in patients with gastric cancer, response to preoperative
      chemotherapy can be predicted by FDG-PET early during the course of therapy. By
      avoiding the morbidity and costs of ineffective therapy, FDG-PET imaging may
      markedly facilitate the use of preoperative chemotherapy.

PMID- 14673050
TI  - Expanded experience with an intradermal skin test to predict for the presence or
      absence of carboplatin hypersensitivity.
AB  - PURPOSE: Carboplatin-associated hypersensitivity is increasingly recognized as a
      potentially serious toxicity when this agent is administered for more than six
      total cycles. PATIENTS AND METHODS: Our group has used a predictive skin test in
      women with gynecologic cancers who have previously received more than six
      cumulative cycles of platinum-based chemotherapy. Thirty minutes before all
      subsequent carboplatin courses, a 0.02-mL aliquot from the solution prepared for
      treatment is injected intradermally. A positive test is considered to be a > or =
      5-mm wheal, with a surrounding flare. RESULTS: From October 1998 through March
      2003, 126 patients received a total of 717 carboplatin skin tests (median per
      patient, four tests; range, one to 54 tests). Of the 668 negative tests (93% of
      the total performed), 10 were associated with evidence of carboplatin
      hypersensitivity (1.5% false-negative rate; 95% CI, 0.6% to 2.4%), none of which
      were severe (eg, dyspnea, hypotension, cardiac/respiratory compromise). Of the 41
      positive tests, the decision was made to not deliver the drug to 32 patients,
      although seven women ultimately underwent a future attempt at re-treatment with a
      platinum agent using a desensitization program. In seven episodes where patients
      received the carboplatin despite the finding of a positive test, six were
      associated with the development of symptoms of anaphylaxis (none severe).
      CONCLUSION: A negative carboplatin skin test seems to predict with reasonable
      reliability for the absence of a severe hypersensitivity reaction with the
      subsequent drug infusion. The implications of a positive test remain less
      certain, but limited experience with continued treatment suggests this approach
      must be undertaken with considerable caution.

PMID- 14673051
TI  - Itraconazole prevents invasive fungal infections in neutropenic patients treated
      for hematologic malignancies: evidence from a meta-analysis of 3,597 patients.
AB  - PURPOSE: Efficacy of antifungal prophylaxis has not yet been convincingly proven
      in numerous trials of various antifungals. New evidence and the anti-Aspergillus
      efficacy of itraconazole prompted a new look at the data for the prevention of
      invasive fungal infections. PATIENTS AND METHODS: Randomized, controlled studies
      with itraconazole for antifungal prophylaxis in neutropenic patients with
      hematologic malignancies were identified from electronic databases and hand
      searching. RESULTS: Thirteen randomized trials included 3,597 patients who were
      assessable for invasive fungal infections. Itraconazole reduced the incidence of
      invasive fungal infection (mean relative risk reduction, 40% +/- 13%; P =.002),
      the incidence of invasive yeast infections (mean, 53% +/- 19%; P =.004) and the
      mortality from invasive fungal infections (mean, 35% +/- 17%; P =.04)
      significantly. The incidence of invasive Aspergillus infections was only reduced
      in trials using the itraconazole cyclodextrine solution (mean, 48% +/- 21%; P
      =.02) and not itraconazole capsules (mean, 75% +/- 73% increase; P =.3). The
      overall mortality was not changed. Adverse effects were rare, hypokalemia was
      noted in three studies, and a higher rate of drug discontinuation was found in
      trials that compared itraconazole cyclodextrine solution to a control without
      cyclodextrine. The effect of prophylaxis was clearly associated with a higher
      bioavailable dose of itraconazole. CONCLUSION: Antifungal prophylaxis with
      itraconazole effectively prevents proven invasive fungal infections and-shown for
      the first time for antifungal prophylaxis-reduces mortality from these infections
      and the rate of invasive Aspergillus infections in neutropenic patients with
      hematologic malignancies. Adequate doses of the oral cyclodextrine solution (at
      least 400 mg/d) or i.v. formulations (200 mg/d) of itraconazole are necessary for
      these effects.

PMID- 14673052
TI  - Are older cancer patients being referred to oncologists? A mail questionnaire of
      Ontario primary care practitioners to evaluate their referral patterns.
AB  - PURPOSE: Understanding why older patients are frequently underrepresented in
      cancer services use and clinical research may help to increase their
      participation in clinical trials and eventually result in better cancer care for
      this vulnerable population. METHODS: To identify potential barriers that may
      prevent older cancer patients from being referred from a primary care physician
      (PCP) to an oncology specialist, a self-administered questionnaire was mailed to
      9,312 PCPs throughout Ontario. RESULTS: With a one-time mailing, 2,240
      questionnaires were returned (response rate, 24%) of which 2,089 (93%) were
      assessable. Although 86% of respondents would refer most older patients with
      early-stage, potentially curable cancers to oncologists, only 65% would refer
      those with advanced-stage, potentially incurable cancers. The factors that most
      influence referral decisions of PCPs are patient's desire to be referred (69%),
      type (54%) and stage (49%) of cancer, and severity of cancer symptoms (49%).
      Other factors including age do not seem to influence the referral decision.
      Approximately 9% of respondents found it difficult to refer older cancer patients
      to oncology specialists, with the most commonly cited barriers being the length
      of waiting lists, mandatory tissue diagnosis before referral, and the belief that
      oncologists seldom relate to PCPs. CONCLUSION: Most PCPs stated that they would
      refer all elderly patients with cancer to oncologists and that referral decisions
      were based mainly on patients' wishes. Continued efforts are needed to overcome
      barriers in the referral process and to understand the perspectives of elderly
      patients to enhance their cancer care.

PMID- 14673053
TI  - Differential effects of paroxetine on fatigue and depression: a randomized,
      double-blind trial from the University of Rochester Cancer Center Community
      Clinical Oncology Program.
AB  - PURPOSE: Fatigue and depression typically occur together in cancer patients,
      suggesting a common etiology, perhaps based on serotonin. This randomized
      clinical trial tested whether paroxetine, a selective serotonin reuptake
      inhibitor antidepressant known to modulate brain serotonin, would reduce fatigue
      in cancer patients and whether any reduction was related to depression. PATIENTS
      AND METHODS: Cancer patients undergoing chemotherapy for the first time were
      assessed for fatigue. Of 704 patients who reported fatigue at their second
      chemotherapy cycle, 549 patients were randomly assigned to receive either 20 mg
      of oral paroxetine hydrochloride daily or placebo for 8 weeks. The assessments of
      fatigue and depression were performed at cycles 3 and 4 of chemotherapy. RESULTS:
      A total of 244 patients treated with paroxetine and 235 patients treated with
      placebo provided assessable data. No difference was detected in fatigue between
      patient groups. At the end of the study, there was a difference between groups in
      the mean level of depression (Center for Epidemiologic Studies Depression scores,
      12.0 v 14.8, respectively; P <.01). CONCLUSION: Paroxetine had no influence on
      fatigue in patients receiving chemotherapy. A possible explanation is that cancer
      related fatigue does not involve a reduction in brain 5-HT levels.

PMID- 14673054
TI  - Revised recommendations of the International Working Group for Diagnosis,
      Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards
      for Therapeutic Trials in Acute Myeloid Leukemia.
AB  - An International Working Group met to revise the diagnostic and response criteria
      for acute myelogenous leukemia originally published in 1990, as well as to
      provide definitions of outcomes and reporting standards to improve
      interpretability of data and comparisons among trials. Since the original
      publication, there have been major advances in our understanding of the biology
      and molecular genetics of acute leukemia that are clinically relevant and warrant
      incorporation into response definitions. Differences from the 1990
      recommendations included a category of leukemia-free state, new criteria for
      complete remission, including cytogenetic and molecular remissions and remission
      duration. Storage of viable blasts for correlative studies is important for
      future progress in the therapy of these disorders.

PMID- 14673055
TI  - Complications of therapy and a diagnostic dilemma case. Case 1. Radiation
      maculopathy following treatment of nasopharyngeal carcinoma.

PMID- 14673056
TI  - Complications of therapy and a diagnostic dilemma case. Case 2. Cutaneous
      toxicity induced by cetuximab.

PMID- 14673057
TI  - Complications of therapy and a diagnostic dilemma case. Case 3. Diagnostic
      dilemma: sarcoidosis simulating metastatic malignancy.

PMID- 14673059
TI  - Quality of life after treatment for prostate cancer: no difference between
      surgery and radiotherapy?

PMID- 14673061
TI  - Eicosapentaenoic acid as a targeted therapy for cancer cachexia.

PMID- 14673060
TI  - Superiority of letrozole over tamoxifen in the first-line treatment of metastatic
      breast cancer patients with normal serum Her-2/neu levels: question of tamoxifen
      resistance.

PMID- 14673063
TI  - Phase I trials: physician and patient perceptions.

PMID- 14673067
TI  - Benefits of locoregional treatment.

PMID- 14673068
TI  - Hereditary breast cancer: shared communication and care.

PMID- 14673070
TI  - Preoperative therapy versus immediate surgery in nonmetastatic osteosarcoma.

PMID- 14673072
TI  - Divergent tRNA-like element supports initiation, elongation, and termination of
      protein biosynthesis.
AB  - The cricket paralysis virus internal ribosome entry site (IRES) can, in the
      absence of canonical initiation factors and initiator tRNA (Met-tRNAi), occupy
      the ribosomal P-site and assemble 80S ribosomes. Here we show that the IRES
      assembles mRNA-80S ribosome complexes by recruitment of 60S subunits to preformed
      IRES-40S complexes. Addition of eukaryotic elongation factors eEF1A and eEF2 and
      aminoacylated elongator tRNAs resulted in the synthesis of peptides, implying
      that the IRES RNA itself mimics the function of Met-tRNAi in the P-site to
      trigger the first translocation step without peptide bond formation. IRES-80S
      complexes that contained a stop codon in the A-site recruited eukaryotic release
      factor eRF1, resulting in ribosome rearrangements in a surprisingly eEF2
      dependent manner. Thus, this P-site-occupying IRES directs the assembly of 80S
      ribosomes, sets the translational reading frame, and mimics the functions of both
      Met-tRNAi and peptidyl tRNA to support elongation and termination.

PMID- 14673073
TI  - Controlling system dimension: a class of real systems that obey the Kaplan-Yorke
      conjecture.
AB  - The Kaplan-Yorke conjecture suggests a simple relationship between the fractal
      dimension of a system and its Lyapunov spectrum. This relationship has important
      consequences in the broad field of nonlinear dynamics where dimension and
      Lyapunov exponents are frequently used descriptors of system dynamics. We develop
      an experimental system with controllable dimension by making use of the Kaplan
      Yorke conjecture. A rectangular steel plate is driven with the output of a
      chaotic oscillator. We controlled the Lyapunov exponents of the driving and then
      computed the fractal dimension of the plate's response. The Kaplan-Yorke
      relationship predicted the system's dimension extremely well. This finding
      strongly suggests that other driven linear systems will behave similarly. The
      ability to control the dimension of a structure's vibrational response is
      important in the field of vibration-based structural health monitoring for the
      robust extraction of damage-sensitive features.

PMID- 14673074
TI  - Structural and functional characterization of the VirB5 protein from the type IV
      secretion system encoded by the conjugative plasmid pKM101.
AB  - Type IV secretion systems mediate intercellular transfer of macro-molecules via a
      mechanism ancestrally related to that of bacterial conjugation machineries. TraC
      of the IncN plasmid pKM101 belongs to the VirB5 family of proteins, an essential
      component of most type IV secretion systems. Here, we present the structure of
      TraC. VirB5/TraC is a single domain protein, which consists of a three helix
      bundle and a loose globular appendage. Structure-based site-directed mutagenesis
      followed by functional studies indicates that VirB5 proteins participate in
      protein-protein interactions important for pilus assembly and function.

PMID- 14673075
TI  - Transcriptome analysis of chlamydial growth during IFN-gamma-mediated persistence
      and reactivation.
AB  - Chlamydia trachomatis is an obligatory intracellular prokaryotic parasite that
      causes a spectrum of clinically important chronic inflammatory diseases of
      humans. Persistent infection may play a role in the pathophysiology of chlamydial
      disease. Here we describe the chlamydial transcriptome in an in vitro model of
      IFN-gamma-mediated persistence and reactivation from persistence. Tryptophan
      utilization, DNA repair and recombination, phospholipid utilization, protein
      translation, and general stress genes were up-regulated during persistence. Down
      regulated genes included chlamydial late genes and genes involved in proteolysis,
      peptide transport, and cell division. Persistence was characterized by altered
      but active biosynthetic processes and continued replication of the chromosome. On
      removal of IFN-gamma, chlamydiae rapidly reentered the normal developmental cycle
      and reversed transcriptional changes associated with cytokine treatment. The
      coordinated transcriptional response to IFN-gamma implies that a chlamydial
      response stimulon has evolved to control the transition between acute and
      persistent growth of the pathogen. In contrast to the paradigm of persistence as
      a general stress response, our findings suggest that persistence is an
      alternative life cycle used by chlamydiae to avoid the host immune response.

PMID- 14673076
TI  - Dynamic analysis of larval locomotion in Drosophila chordotonal organ mutants.
AB  - Rhythmic movements, such as peristaltic contraction, are initiated by output from
      central pattern generator (CPG) networks in the CNS. These oscillatory networks
      elicit locomotion in the absence of external sensory or descending inputs, but
      CPG circuits produce more directed and behaviorally relevant movement via
      peripheral nervous system (PNS) input. Drosophila melanogaster larval locomotion
      results from patterned muscle contractions moving stereotypically along the body
      segments, but without PNS feedback, contraction of body segments is
      uncoordinated. We have dissected the role of a subset of mechanosensory neurons
      in the larval PNS, the chordotonal organs (chos), in providing sensory feedback
      to the locomotor CPG circuit with dias (Dynamic Image Analysis System) software.
      We analyzed mutants carrying cho mutations including atonal, a cho proneural
      gene, beethoven, a cho cilia class mutant, smetana and touch-insensitive larva B,
      two axonemal mutants, and 5D10, a weak cho mutant. All cho mutants have defects
      in gross path morphology compared to controls. These mutants exhibit increased
      frequency and duration of turning (decision-making) and reduced duration of
      linear locomotion. Furthermore, cho mutants affect locomotor parameters,
      including reduced average speed, direction change, and persistence. Dias analysis
      of peristaltic waves indicates that mutants exhibit reduced average speed,
      positive flow and negative flow, and increased stride period. Thus, cho sensilla
      are major proprioceptive components that underlie touch sensitivity, locomotion,
      and peristaltic contraction by providing sensory feedback to the locomotor CPG
      circuit in larvae.

PMID- 14673077
TI  - Divergence of Hoxc8 early enhancer parallels diverged axial morphologies between
      mammals and fishes.
AB  - There is considerable interest in understanding how cis-regulatory modifications
      drive morphological changes across species. Because developmental regulatory
      genes, including Hox genes, are remarkably conserved, their noncoding regulatory
      regions are likely sources for variations. Modifications of Hox cis-regulatory
      elements have potential to alter Hox gene expression and, hence, axial
      morphologies. In vertebrates, differences in the axial levels of Hox gene
      expression correlate with differences in the number and relative position of
      thoracic vertebrae. Variation in cis-regulatory elements of Hox genes can be
      identified by comparative sequence and reporter gene analyses in transgenic mouse
      embryos. Using these approaches, we show a remarkable divergence of the Hoxc8
      early enhancers between mammals and fishes representing diverse axial
      morphologies. Extensive restructuring of the Hoxc8 early enhancer including
      nucleotide substitutions, inversion, and divergence result in distinct patterns
      of reporter gene expression along the embryonic axis. Our results provide an
      evolutionary perspective on how the enhancer elements are engineered and support
      the hypothesis that remodeling of Hox regulatory elements in different species
      has played a significant role in generating morphological diversity.

PMID- 14673078
TI  - Fear of novelty in infant rats predicts adult corticosterone dynamics and an
      early death.
AB  - Individuals who are fearful of novelty have a larger hypothalamic-pituitary
      adrenal axis response than do nonfearful individuals. We hypothesized that a
      fearful behavioral style emerging early in life would be associated with life
      long altered adrenal activity. Because there is ample physiological evidence both
      costs and benefits of adrenal activation, we determined whether such a stable
      emotional-neuroendocrine trait was associated with differential morbidity and
      mortality. To conduct such lifespan work, we studied a relatively short-lived
      mammal: the Norway rat. We first established that an animal's hesitation or
      willingness to explore a novel environment ("neophobia" and "neophilia,"
      respectively) is an identifiable and stable behavioral trait in young-adult males
      and that neophobia, compared with neophilia, was associated with a greater
      glucocorticoid response to novelty. Second, we were able to detect behavioral
      differences among infant rats within a family, and this behavioral disposition at
      infancy predicted the magnitude of the glucocorticoid response in late middle
      age. Males identified as neophobic during infancy died sooner than their less
      fearful brothers. Although both types of males died with similar pathologies
      (tumors), neophobic males were 60% more likely to die at any point in time. This
      lifespan study identifies an emotional trait in infancy that predicts an early
      death and an associated neuroendocrine trait in adulthood that is a potential
      mechanism underlying the relationship between behavioral style and longevity.

PMID- 14673079
TI  - Structure of Mth11/Mth Rpp29, an essential protein subunit of archaeal and
      eukaryotic RNase P.
AB  - We have determined the solution structure of Mth11 (Mth Rpp29), an essential
      subunit of the RNase P enzyme from the archaebacterium Methanothermobacter
      thermoautotrophicus (Mth). RNase P is a ubiquitous ribonucleoprotein enzyme
      primarily responsible for cleaving the 5' leader sequence during maturation of
      tRNAs in all three domains of life. In eubacteria, this enzyme is made up of two
      subunits: a large RNA ( approximately 120 kDa) responsible for mediating
      catalysis, and a small protein cofactor ( approximately 15 kDa) that modulates
      substrate recognition and is required for efficient in vivo catalysis. In
      contrast, multiple proteins are associated with eukaryotic and archaeal RNase P,
      and these proteins exhibit no recognizable homology to the conserved bacterial
      protein subunit. In reconstitution experiments with recombinantly expressed and
      purified protein subunits, we found that Mth Rpp29, a homolog of the Rpp29
      protein subunit from eukaryotic RNase P, is an essential protein component of the
      archaeal holoenzyme. Consistent with its role in mediating protein-RNA
      interactions, we report that Mth Rpp29 is a member of the
      oligonucleotide/oligosaccharide binding fold family. In addition to a structured
      beta-barrel core, it possesses unstructured N- and C-terminal extensions bearing
      several highly conserved amino acid residues. To identify possible RNA contacts
      in the protein-RNA complex, we examined the interaction of the 11-kDa protein
      with the full 100-kDa Mth RNA subunit by using NMR chemical shift perturbation.
      Our findings represent a critical step toward a structural model of the RNase P
      holoenzyme from archaebacteria and higher organisms.

PMID- 14673080
TI  - Transgenic mouse model for echovirus myocarditis and paralysis.
AB  - Echoviruses have been implicated in multiple human disease syndromes, including
      aseptic meningitis, paralysis, and heart disease, but no animal model is
      available for studying the pathogenesis of infection. Production of human
      integrin very late antigen 2, a receptor for echovirus type 1, in transgenic mice
      conferred susceptibility to viral infection. Intracerebral inoculation of newborn
      transgenic mice with echovirus leads to paralysis and wasting. No disease was
      observed in infected nontransgenic mice. In paralyzed mice significant damage was
      observed in the outer layers of the cerebrum, and numerous condensed neuronal
      nuclei were present. In contrast, intracerebral inoculation of adolescent (3- to
      4-week-old) transgenic mice with echovirus type 1 did not lead to paralysis but
      an acute wasting phenotype and myocarditis. These findings establish human very
      late antigen 2 transgenic mice as a model for echovirus pathogenesis.

PMID- 14673081
TI  - Anion exchanger 2 is essential for spermiogenesis in mice.
AB  - Na+-independent anion exchangers (AE) mediate electroneutral exchange of Cl- for
      HCO3- ions across cell membranes, being involved in intracellular pH and cell
      volume regulation and in transepithelial hydroionic fluxes. Bicarbonate
      activation of adenylyl cyclase is known to be necessary for sperm motility and
      sperm capacitation, and a few studies have suggested a possible role of AE
      carriers in reproduction. Among the four AE genes identified in mammals thus far,
      only Ae2 (Slc4a2) has been determined to be expressed in the male reproductive
      system, especially in developing spermatozoa and in epididymal epithelium. Most
      AE genes drive alternative transcription, which in mouse Ae2 results in several
      Ae2 isoforms. Here, we generated mice carrying a targeted disruption of Ae2 that
      prevents the expression of the three AE2 isoforms (Ae2a, Ae2b1, and Ae2b2)
      normally found in mouse testes. Male Ae2-/- mice (but not female Ae2-/- mice) are
      infertile. Histopathological analysis of Ae2-/- testes shows an interruption of
      spermiogenesis, with only a few late spermatids and a complete absence of
      spermatozoa in the seminiferous tubules. The number of apoptotic bodies is
      increased in the seminiferous tubules and in the epididymis, which also shows
      squamous metaplasia of the epididymal epithelium. Our findings reveal an
      essential role of Ae2 in mouse spermiogenesis and stress the recently postulated
      involvement of bicarbonate in germ-cell differentiation through the bicarbonate
      sensitive soluble-adenylyl-cyclase pathway.

PMID- 14673082
TI  - Glucose transporter-1-deficient mice exhibit impaired development and deformities
      that are similar to diabetic embryopathy.
AB  - The hyperglycemia of maternal diabetes suppresses the glucose transporter-1
      (GLUT1) facilitative glucose transporter 49-66% in preimplantation embryos.
      Glucose uptake is reduced and apoptosis is activated. We hypothesized that the
      reduction of embryonic GLUT1 may play a key role in the malformations of diabetic
      embryopathy. Therefore, we produced GLUT1-deficient transgenic mice [i.e.,
      antisense-GLUT1 (GT1AS)] to determine whether GLUT1 deficiency alone could
      reproduce the growth defects. Early cell division of fertilized mouse eggs
      injected with GT1AS was markedly impaired, P < 0.001 vs. controls. Two
      populations of preimplantation embryos obtained from GT1AS x GT1AS heterozygote
      matings exhibited reduction of the 2-deoxyglucose uptake rate: one by 50%
      (presumed heterozygotes, P < 0.001 vs. control) and the other by 95% (presumed
      homozygotes, P < 0.001 vs. heterozygotes). Embryonic GLUT1 deficiency in the
      range reported with maternal diabetes was associated with growth retardation and
      developmental malformations similar to those described in diabetes-exposed
      embryos: intrauterine growth retardation (31.1%), caudal regression (9.8%),
      anencephaly with absence of the head (6.6%), microphthalmia (4.9%), and
      micrognathia (1.6%). Reduced body weight (small embryos, <70% of the
      nontransgenic body weight) was accompanied by other malformations and a 56%
      reduction of GLUT1 protein, P < 0.001 vs. nonsmall embryos (body weight >or=70%
      normal). The heart, brain, and kidneys of embryonic day 18.5 GT1AS embryos
      exhibited 24-51% reductions of GLUT1 protein. The homozygous GT1AS genotype was
      lethal during gestation. Reduced embryonic GLUT1 was associated with the
      appearance of apoptosis. Therefore, GLUT1 deficiency may play a role in producing
      embryonic malformations resulting from the hyperglycemia of maternal diabetes.
      Late gestational macrosomia was absent, apparently requiring a different
      mechanism.

PMID- 14673083
TI  - A bacterial group II intron favors retrotransposition into plasmid targets.
AB  - Group II introns, widely believed to be the ancestors of nuclear pre-mRNA
      introns, are catalytic RNAs found in bacteria, archaea, and eukaryotes. They are
      mobile genetic elements that move via an RNA intermediate. They retrohome to
      intronless alleles and retrotranspose to ectopic sites, aided by an intron
      encoded protein with reverse transcriptase, maturase, and endonuclease
      activities. Many group II introns identified in bacteria reside on plasmid
      genomes rather than bacterial chromosomes, implying that plasmids are havens for
      these retroelements. This study demonstrates that almost one-fourth of
      retrotransposition events of the Ll.LtrB intron in Lactococcus lactis are into
      the plasmid donor. This level is more than twice that predicted based on target
      size and plasmid copy number relative to the chromosome. In particular, the
      fraction of such plasmid targeting events was elevated to more than one-third of
      retrotransposition events by mutation of the intron-encoded endonuclease, a
      situation that may resemble most bacterial group II introns, which lack the
      endonuclease. Target-site sequences on the plasmid are more relaxed than those on
      the chromosome, likely accounting for preferred integration into plasmid
      replicons. Furthermore, the direction of integration relative to promoters and
      origins of replication is consistent with group II intron retrotransposition into
      single-stranded DNA at replication forks. This work provides mechanistic
      rationales for the prevalence of group II introns in natural plasmid populations
      and underscores that targeting to plasmids, which are themselves mobile elements,
      could promote intron spread.

PMID- 14673084
TI  - Encephalization and allometric trajectories in the genus Homo: evidence from the
      Neandertal and modern lineages.
AB  - The term "encephalization" is commonly used to describe an enlargement in brain
      size, considered as either absolute endocranial volumes or relative values in
      relation to body size. It is widely recognized that a considerable endocranial
      expansion occurred throughout the evolution of the genus Homo. This article aims
      to evaluate whether this phenomenon was the outcome of distinct evolutionary
      lineages, reaching similar brain expansions but through different trajectories.
      Endocranial morphology was studied in a sample of fossil hominines by
      multivariate approaches using both traditional metrics and geometric
      morphometrics. The analysis was focused on the transition from a generalized
      archaic pattern within the genus Homo to the modern morphology and compared with
      changes that occurred along the Neandertal lineage. The main result was the
      identification of two different evolutionary trajectories, in which a similar
      expansion in endocranial size has been reached by different changes in shape.
      Along the Neandertal lineage we observed maintenance of an "archaic" endocranial
      model, in which a large amount of variability is based on a single allometric
      trend. By contrast, when modern endocasts were compared with nonmodern ones, we
      found important differences apparently led by a parietal expansion. In this
      light, the origin of our species may have represented the opportunity to surpass
      the constraints imposed on encephalization by the ontogenetic pattern shared by
      nonmodern Homo representatives.

PMID- 14673085
TI  - The kinesin KIF17b and RNA-binding protein TB-RBP transport specific cAMP
      responsive element modulator-regulated mRNAs in male germ cells.
AB  - Testis brain RNA-binding protein (TB-RBP), the mouse orthologue of the human
      protein Translin, is a widely expressed and highly conserved protein with
      proposed functions in chromosomal translocations, mitotic cell division, and mRNA
      transport, stabilization, and storage. Targeted inactivation of TB-RBP leads to
      abnormalities in fertility and behavior. A testis-enriched kinesin KIF17b
      coimmunoprecipitates with TB-RBP in a RNA-protein complex containing specific
      cAMP-responsive element modulator (CREM)-regulated mRNAs. The specificity of this
      interaction is confirmed by in vivo RNA-protein crosslinking and transfections of
      hippocampal neurons. Combining in situ hybridization and immunohistochemistry at
      the electron microscope level, a temporally sequential dissociation of KIF17b and
      TB-RBP from specific mRNAs is detected with TB-RBP release coincident with the
      time of mRNA translation, indicating a separation of the processes of transport
      and translation. We conclude that KIF17b serves as a molecular motor component of
      a TB-RBP-mouse ribonucleoprotein complex transporting a group of specific CREM
      regulated mRNAs in mammalian male postmeiotic germ cells. Because KIF17b has been
      reported to control CREM-dependent transcription in male germ cells by regulating
      the intracellular location of the transcriptional coactivator activator of CREM
      in testis, this indicates that one kinesin links the processes of transcription
      and transport of specific mRNAs in mammalian male germ cells.

PMID- 14673086
TI  - Gi protein activation in intact cells involves subunit rearrangement rather than
      dissociation.
AB  - G protein-coupled receptors transduce diverse extracellular signals, such as
      neurotransmitters, hormones, chemokines, and sensory stimuli, into intracellular
      responses through activation of heterotrimeric G proteins. G proteins play
      critical roles in determining specificity and kinetics of subsequent biological
      responses by modulation of effector proteins. We have developed a fluorescence
      resonance energy transfer (FRET)-based assay to directly measure mammalian G
      protein activation in intact cells and found that Gi proteins activate within 1-2
      s, which is considerably slower than activation kinetics of the receptors
      themselves. More importantly, FRET measurements demonstrated that Galphai- and
      Gbetagamma-subunits do not dissociate during activation, as has been previously
      postulated. Based on FRET measurements between Galphai-yellow fluorescent protein
      and Gbetagamma-subunits that were fused to cyan fluorescent protein at various
      positions, we conclude that, instead, G protein subunits undergo a molecular
      rearrangement during activation. The detection of a persistent heterotrimeric
      composition during G protein activation will impact the understanding of how G
      proteins achieve subtype-selective coupling to effectors. This finding will be of
      particular interest for unraveling Gbetagamma-induced signaling pathways.

PMID- 14673087
TI  - Hairpin-bisulfite PCR: assessing epigenetic methylation patterns on complementary
      strands of individual DNA molecules.
AB  - Epigenetic inheritance, the transmission of gene expression states from parent to
      daughter cells, often involves methylation of DNA. In eukaryotes, cytosine
      methylation is a frequent component of epigenetic mechanisms. Failure to transmit
      faithfully a methylated or an unmethylated state of cytosine can lead to altered
      phenotypes in plants and animals. A central unresolved question in epigenetics
      concerns the mechanisms by which a locus maintains, or changes, its state of
      cytosine methylation. We developed "hairpin-bisulfite PCR" to analyze these
      mechanisms. This method reveals the extent of methylation symmetry between the
      complementary strands of individual DNA molecules. Using hairpin-bisulfite PCR,
      we determined the fidelity of methylation transmission in the CpG island of the
      FMR1 gene in human lymphocytes. For the hypermethylated CpG island of this gene,
      characteristic of inactive-X alleles, we estimate a maintenance methylation
      efficiency of approximately 0.96 per site per cell division. For de novo
      methylation efficiency (E(d)), remarkably different estimates were obtained for
      the hypermethylated CpG island (E(d) = 0.17), compared with the hypomethylated
      island on the active-X chromosome (E(d) < 0.01). These results clarify the
      mechanisms by which the alternative hypomethylated and hypermethylated states of
      CpG islands are stably maintained through many cell divisions. We also analyzed a
      region of human L1 transposable elements. These L1 data provide accurate
      methylation patterns for the complementary strand of each repeat sequence
      analyzed. Hairpin-bisulfite PCR will be a powerful tool in studying other
      processes for which genetic or epigenetic information differs on the two
      complementary strands of DNA.

PMID- 14673088
TI  - Primitive adult hematopoietic stem cells can function as osteoblast precursors.
AB  - Osteoblasts are continually recruited from stem cell pools to maintain bone.
      Although their immediate precursor is a plastic-adherent mesenchymal stem cell
      able to generate tissues other than bone, increasing evidence suggests the
      existence of a more primitive cell that can differentiate to both hematopoietic
      and mesenchymal cells. We show here that the "side population" (SP) of marrow
      stem cells, defined by their ability to rapidly expel a DNA-binding dye and to
      regenerate the hematopoietic compartment, can differentiate to osteoblasts
      through a mesenchymal intermediate. When transplanted into lethally irradiated
      mice, single gene-marked murine SP cells reconstituted depleted osteoprogenitor
      pools, such that a large proportion of the osteogenic cells in the epiphysis of
      long bone carried the donor SP cell marker. These findings suggest that the
      developmental capacity of SP cells is not restricted to the hematopoietic
      lineages but extends to osteogenic differentiation. This property not only
      elucidates a previously unrecognized step in osteoblast development, but also has
      intriguing implications for the use of SP cells in clinical orthopedics and stem
      cell-based disorders of bone.

PMID- 14673089
TI  - Polariton lasing vs. photon lasing in a semiconductor microcavity.
AB  - Nearly one decade after the first observation of Bose-Einstein condensation in
      atom vapors and realization of matter-wave (atom) lasers, similar concepts have
      been demonstrated recently for polaritons: half-matter, half-light quasiparticles
      in semiconductor microcavities. The half-light nature of polaritons makes
      polariton lasers promising as a new source of coherent and nonclassical light
      with extremely low threshold energy. The half-matter nature makes polariton
      lasers a unique test bed for many-body theories and cavity quantum
      electrodynamics. In this article, we present a series of experimental studies of
      a polariton laser, exploring its properties as a relatively dense degenerate Bose
      gas and comparing it to a photon laser achieved in the same structure. The
      polaritons have an effective mass that is twice the cavity photon effective mass,
      yet seven orders of magnitude less than the hydrogen atom mass; hence, they can
      potentially condense at temperatures seven orders of magnitude higher than those
      required for atom Bose-Einstein condensations. Accompanying the phase transition,
      a polariton laser emits coherent light but at a threshold carrier density two
      orders of magnitude lower than that needed for a normal photon laser in a same
      structure. It also is shown that, beyond threshold, the polariton population
      splits to a thermal equilibrium Bose-Einstein distribution at in-plane wave
      number k parallel > 0 and a nonequilibrium condensate at k parallel approximately
      0, with a chemical potential approaching to zero. The spatial distributions and
      polarization characteristics of polaritons also are discussed as unique
      signatures of a polariton laser.

PMID- 14673090
TI  - The low-spin heme of cytochrome c oxidase as the driving element of the proton
      pumping process.
AB  - Mitochondrial cytochrome c oxidase plays an essential role in aerobic cellular
      respiration, reducing dioxygen to water in a process coupled with the pumping of
      protons across the mitochondrial inner membrane. An aspartate residue, Asp-51,
      located near the enzyme surface, undergoes a redox-coupled x-ray structural
      change, which is suggestive of a role for this residue in redox-driven proton
      pumping. However, functional or mechanistic evidence for the involvement of this
      residue in proton pumping has not yet been obtained. We report that the Asp-51 -
      > Asn mutation of the bovine enzyme abolishes its proton-pumping function without
      impairment of the dioxygen reduction activity. Improved x-ray structures (at
      1.8/1.9-A resolution in the fully oxidized/reduced states) show that the net
      positive charge created upon oxidation of the low-spin heme of the enzyme drives
      the active proton transport from the interior of the mitochondria to Asp-51
      across the enzyme via a water channel and a hydrogen-bond network, located in
      tandem, and that the enzyme reduction induces proton ejection from the aspartate
      to the mitochondrial exterior. A peptide bond in the hydrogen-bond network
      critically inhibits reverse proton transfer through the network. A redox-coupled
      change in the capacity of the water channel, induced by the hydroxyfarnesylethyl
      group of the low-spin heme, suggests that the channel functions as an effective
      proton-collecting region. Infrared results indicate that the conformation of Asp
      51 is controlled only by the oxidation state of the low-spin heme. These results
      indicate that the low-spin heme drives the proton-pumping process.

PMID- 14673091
TI  - Dissociation of spikes, synaptic activity, and activity-dependent increments in
      rat cerebellar blood flow by tonic synaptic inhibition.
AB  - Functional neuroimaging relies on the robust coupling between neuronal activity,
      metabolism and cerebral blood flow (CBF) to map the brain, but the physiological
      basis of the neuroimaging signals is still not well understood. Here we applied a
      pharmacological approach to separate spiking activity, synaptic activity, and the
      accompanying changes in CBF in rat cerebellar cortex. We report that tonic
      synaptic inhibition achieved by topical application of gamma-aminobutyric acid
      type A (GABAA) (muscimol) or GABAB (baclofen) receptor agonists abolished or
      reduced spontaneous Purkinje cell spiking activity without affecting basal CBF.
      The magnitude of CBF responses evoked by climbing fiber stimulation decreased
      gradually over time after exposure to muscimol, being more pronounced in the
      superficial than in the deep cortical layers. We provide direct evidence in favor
      of a laminar-specific regulation of CBF in deep cortical layers, independent of
      dilatation of surface vessels. With prolonged exposure to muscimol, activity
      dependent CBF increments disappeared, despite preserved cerebrovascular
      reactivity to adenosine and preserved local field potentials (LFP). This
      dissociation of CBF and LFPs suggests that CBF responses are independent of
      extracellular synaptic currents that generate LFPs. Our work implies that
      neuronal and vascular signals evoked by glutamatergic pathways are sensitive to
      synaptic inhibition, and that local mechanisms independent of transmembrane
      synaptic currents adjust flow to synaptic activity in distinct cortical layers.
      Our results provide fundamental insights into the functional regulation of blood
      flow, showing important interference of GABAA receptors in translating excitatory
      input into blood flow responses.

PMID- 14673092
TI  - Murine and human zona pellucida 3 derived from mouse eggs express identical O
      glycans.
AB  - Murine sperm initiate fertilization by binding to the outer covering of the egg
      known as the murine zona pellucida (mZP). This binding is thought to require the
      interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg
      binding proteins coating the sperm plasma membrane. The precise molecular basis
      of this interaction remains to be resolved. In this study, we analyzed the O
      glycosylation of the individual mZP glycoproteins by using ultrasensitive MS
      methods. We found that the majority of the O-glycans that are linked to mZP3 are
      core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc),
      lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1
      4]Galbeta1-4 (Sda antigen). Many of these terminal sequences have been implicated
      previously in murine sperm-egg binding. Core type 1 O-glycans are also present
      and are generally unmodified, although some are terminated with sialic acid, beta
      linked N-acetylhexosamine, or NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4. Eggs
      expressing human ZP (huZP) glycoprotein huZP3, derived from transgenic mice, bind
      murine but not human sperm, implying that huZP3 acquires the same O-glycans as
      native mZP3. Sequencing of huZP3-associated O-glycans confirms that this
      implication is correct. The data obtained in this investigation may prove to be
      very useful for studies to determine the precise molecular basis of initial
      murine sperm-egg binding.

PMID- 14673093
TI  - Antigen-driven effector CD8 T cell function regulated by T-bet.
AB  - Type 1 immunity relies on the differentiation of two major subsets of T
      lymphocytes, the CD4+ T helper (Th) cell and the CD8+ cytotoxic T cell, that
      direct inflammatory and cytotoxic responses essential for the destruction of
      intracellular and extracellular pathogens. In contrast to CD4 cells, little is
      known about transcription factors that control the transition from the CD8 naive
      to effector cell stage. Here, we report that the transcription factor T-bet,
      known to regulate Th cell differentiation, also controls the generation of the
      CD8+ cytotoxic effector cell. Antigen-driven generation of effector CD8+ cells
      was impaired in OT-I T cell receptor transgenic mice lacking T-bet, resulting in
      diminished cytotoxicity and a marked shift in cytokine secretion profiles.
      Furthermore, mice lacking T-bet responded poorly to infection with lymphocytic
      choriomeningitis virus. T-bet is a key player in the generation of type 1
      immunity, in both Th and T cytotoxic cells.

PMID- 14673094
TI  - Diversity of regulatory CD4+T cells controlling distinct organ-specific
      autoimmune diseases.
AB  - Depletion of selected regulatory CD4+ T cell subsets induces the spontaneous
      onset of various immune or autoimmune disorders. It is not clear, however,
      whether a given subset, notably CD4+CD25+ regulatory T cells, protects from a
      wide spectrum of immune disorders, or whether specialized subsets of regulatory T
      cells control each given disease or group of diseases. We report here, using
      diabetes prone nonobese diabetic (NOD) mice, that depending on the regulatory T
      cells that are depleted, i.e., CD25+, CD62L+, or CD45RB(low), distinct immune
      diseases appear after transfer into NOD severe combined immunodeficiency (SCID)
      recipients. Thus, reconstitution of NOD SCID mice with CD25- T cells induces
      major gastritis and late-onset diabetes, but no or mild colitis. Reconstitution
      with CD62L- T cells induces fulminant diabetes with no colitis or gastritis.
      Reconstitution with CD45RB(high) T cells induces major colitis with wasting
      disease and no or very moderate gastritis and diabetes. Major differences among
      the three regulatory T cell subsets are also seen in vitro. The bulk of
      suppressor cells inhibiting the proliferation of CD4+CD25- T cells in coculture
      is concentrated within the CD25+ but not the CD62L+ or CD45RB(low) T cell
      subsets. Similarly, cytokine production patterns are significantly different for
      each regulatory T cell subset. Collectively, these data point to the diversity
      and organ selectivity of regulatory T cells controlling distinct autoimmune
      diseases whatever the underlying mechanisms.

PMID- 14673095
TI  - Changing identities: tRNA duplication and remolding within animal mitochondrial
      genomes.
AB  - Although the majority of metazoan mitochondrial genomes (mtDNAs) contain the same
      37 genes, including 22 encoding transfer RNAs (tRNAs), the recognition of
      orthologs is not always straightforward. Here we demonstrate that inferring tRNA
      orthologs among taxa by using anticodon triplets and deduced secondary structure
      can be misleading: through a process of tRNA duplication and mutation in the
      anticodon triplet, remolded leucine (LUUR) tRNA genes have repeatedly taken over
      the role of isoaccepting LCUN leucine tRNAs within metazoan mtDNA. In the present
      work, data from within the gastropods and a broad survey of metazoan mtDNA
      suggest that tRNA leucine duplication and remolding events have occurred
      independently at least seven times within three major animal lineages. In all
      cases where the mechanism of gene remolding can be inferred with confidence, the
      direction is the same: from LUUR to LCUN. Gene remolding and its apparent
      asymmetry have significant implications for the use of mitochondrial tRNA gene
      orders as phylogenetic markers. Remolding complicates the identification of
      orthologs and can result in convergence in gene order. Careful sequence-based
      analysis of tRNAs can help to recognize this homoplasy, improving gene-order
      based phylogenetic hypotheses and underscoring the importance of careful homology
      assessment. tRNA remolding also provides an additional mechanism by which gene
      order changes can occur within mtDNA: through the changing identity of tRNA genes
      themselves. Recognition of these remolding events can lead to new interpretations
      of gene order changes, as well as the discovery of phylogenetically relevant gene
      dynamics that are hidden at the level of gene order alone.

PMID- 14673096
TI  - High-affinity salicylic acid-binding protein 2 is required for plant innate
      immunity and has salicylic acid-stimulated lipase activity.
AB  - Salicylic acid (SA) is a critical hormone for signaling innate immunity in
      plants. Here we present the purification and characterization of SA-binding
      protein 2 (SABP2), a tobacco protein that is present in low abundance and
      specifically binds SA with high affinity. Sequence analysis predicted that SABP2
      is a lipase belonging to the alpha/beta fold hydrolase super family. Confirming
      this prediction, recombinant SABP2 exhibited lipase activity against several
      synthetic substrates. Moreover, this lipase activity was stimulated by SA binding
      and may generate a lipid-derived signal. Silencing of SABP2 expression suppressed
      local resistance to tobacco mosaic virus, induction of pathogenesis-related 1 (PR
      1) gene expression by SA, and development of systemic acquired resistance.
      Together, these results suggest that SABP2 is an SA receptor that is required for
      the plant immune response. We further propose that SABP2 belongs to a large class
      of ligand-stimulated hydrolases involved in stress hormone-mediated signal
      transduction.

PMID- 14673097
TI  - Conformations and dynamics of Ets-1 ETS domain-DNA complexes.
AB  - Molecular dynamics studies have been performed for 3.5 ns on the ETS domain of
      Ets-1 transcription factor bound to the 14-bp DNA, d(AGTGCCGGAAATGT), comprising
      the core sequence of high-affinity (GGAA), ETS-GGAA. In like manner, molecular
      dynamics simulations have been carried out for 3.9 ns on the mutant low-affinity
      core sequence, GGAG (ETS-GGAG). Analyses of the DNA backbone of ETS-GGAG show
      conformational interconversions from BI to BII substates. Also, crank shaft
      motions are noticed at the mutated nucleotide base pair step after 1500 ps of
      dynamics. The corresponding nucleotide of ETS-GGAA is characteristic of a BI
      conformation and no crank shaft motions are observed. The single mutation of ETS
      GGAA to ETS-GGAG also results in variations of helical parameters and solvent
      accessible surface area around the major and minor grooves of the DNA. The
      presence of water contacts during the entire simulation proximal to the fourth
      base pair step of core DNA sequence is a characteristic feature of ETS-GGAA. Such
      waters are more mobile in ETS-GGAG at 100 ps and distant after 1500 ps.
      Anticorrelated motions between certain amino acids of Ets-1 protein are
      predominant in ETS-GGAA but less so or absent in the mutant. These motions are
      reflected in the flexibility of amino acid residues of the protein backbone. We
      consider that these conformational features and water contacts are involved in
      stabilizing the hydrogen bond interactions between helix-3 residues of Ets-1 and
      DNA during the transcription process.

PMID- 14673098
TI  - Activation of a LTR-retrotransposon by telomere erosion.
AB  - Retrotransposons can facilitate repair of broken chromosomes, and therefore an
      important question is whether the host can activate retrotransposons in response
      to chromosomal lesions. Here we show that Ty1 elements, which are LTR
      retrotransposons in Saccharomyces cerevisiae, are mobilized when DNA lesions are
      created by the loss of telomere function. Inactivation of telomerase in yeast
      results in progressive shortening of telomeric DNA, eventually triggering a DNA
      damage checkpoint that arrests cells in G2/M. A fraction of cells, termed
      survivors, recover from arrest by forming alternative telomere structures. When
      telomerase is inactivated, Ty1 retrotransposition increases substantially in
      parallel with telomere erosion and then partially declines when survivors emerge.
      Retrotransposition is stimulated at the level of Ty1 cDNA synthesis, causing cDNA
      levels to increase 20-fold or more before survivors form. This response is
      elicited through a signaling pathway that includes Rad24, Rad17, and Rad9, three
      components of the DNA-damage checkpoint. Our findings indicate that Ty1
      retrotransposons are activated as part of the cellular response to telomere
      dysfunction.

PMID- 14673099
TI  - Network component analysis: reconstruction of regulatory signals in biological
      systems.
AB  - High-dimensional data sets generated by high-throughput technologies, such as DNA
      microarray, are often the outputs of complex networked systems driven by hidden
      regulatory signals. Traditional statistical methods for computing low-dimensional
      or hidden representations of these data sets, such as principal component
      analysis and independent component analysis, ignore the underlying network
      structures and provide decompositions based purely on a priori statistical
      constraints on the computed component signals. The resulting decomposition thus
      provides a phenomenological model for the observed data and does not necessarily
      contain physically or biologically meaningful signals. Here, we develop a method,
      called network component analysis, for uncovering hidden regulatory signals from
      outputs of networked systems, when only a partial knowledge of the underlying
      network topology is available. The a priori network structure information is
      first tested for compliance with a set of identifiability criteria. For networks
      that satisfy the criteria, the signals from the regulatory nodes and their
      strengths of influence on each output node can be faithfully reconstructed. This
      method is first validated experimentally by using the absorbance spectra of a
      network of various hemoglobin species. The method is then applied to microarray
      data generated from yeast Saccharamyces cerevisiae and the activities of various
      transcription factors during cell cycle are reconstructed by using recently
      discovered connectivity information for the underlying transcriptional regulatory
      networks.

PMID- 14673100
TI  - Ligand selectivity by seeking hydrophobicity in thyroid hormone receptor.
AB  - Selective therapeutics for nuclear receptors would revolutionize treatment for
      endocrine disease. Specific control of nuclear receptor activity is challenging
      because the internal cavities that bind hormones can be virtually identical. Only
      one highly selective hormone analog is known for the thyroid receptor, GC-24, an
      agonist for human thyroid hormone receptor beta. The compound differs from
      natural hormone in benzyl, substituting for an iodine atom in the 3' position.
      The benzyl is too large to fit into the enclosed pocket of the receptor. The
      crystal structure of human thyroid hormone receptor beta at 2.8-A resolution with
      GC-24 bound explains its agonist activity and unique isoform specificity. The
      benzyl of GC-24 is accommodated through shifts of 3-4 A in two helices. These
      helices are required for binding hormone and positioning the critical helix 12 at
      the C terminus. Despite these changes, the complex associates with coactivator as
      tightly as human thyroid hormone receptor bound to thyroid hormone and is fully
      active. Our data suggest that increased specificity of ligand recognition derives
      from creating a new hydrophobic cluster with ligand and protein components.

PMID- 14673101
TI  - Enhanced biocontrol activity of Trichoderma through inactivation of a mitogen
      activated protein kinase.
AB  - The production of lytic enzymes in Trichoderma is considered determinant in its
      parasitic response against fungal species. A mitogen-activated protein kinase
      encoding gene, tvk1, from Trichoderma virens was cloned, and its role during the
      mycoparasitism, conidiation, and biocontrol was examined in tvk1 null mutants.
      These mutants showed a clear increase in the level of the expression of
      mycoparasitism-related genes under simulated mycoparasitism and during direct
      confrontation with the plant pathogen Rhizoctonia solani. The null mutants
      displayed an increased protein secretion phenotype as measured by the production
      of lytic enzymes in culture supernatant compared to the wild type. Consistently,
      biocontrol assays demonstrated that the null mutants were considerably more
      effective in disease control than the wild-type strain or a chemical fungicide.
      In addition, tvk1 gene disruptant strains sporulated abundantly in submerged
      cultures, a condition that is not conducive to sporulation in the wild type.
      These data suggest that Tvk1 acts as a negative modulator during host sensing and
      sporulation in T. virens.

PMID- 14673102
TI  - Epstein-Barr virus latent membrane protein 1 activation of NF-kappaB through
      IRAK1 and TRAF6.
AB  - Epstein-Barr virus latent membrane protein 1 (LMP1) activation of NF-kappaB is
      critical for Epstein-Barr virus-infected B lymphocyte survival. LMP1 activates
      the IkappaB kinase complex and NF-kappaB through two cytoplasmic signaling
      domains that engage tumor necrosis factor receptor-associated factor
      (TRAF)1/2/3/5 or TRADD and RIP. We now use cells lacking expression of TRAF2,
      TRAF5, TRAF6, IKKalpha, IKKbeta, IKKgamma, TAB2, IL-1 receptor-associated kinase
      (IRAK)1, or IRAK4 to assess their roles in LMP1-mediated NF-kappaB activation.
      LMP1-induced RelA nuclear translocation was similar in IKKalpha knockout (KO) and
      WT murine embryo fibroblasts (MEFs) but substantially deficient in IKKbeta KO
      MEFs. NF-kappaB-dependent promoter responses were also substantially deficient in
      IKKbeta KO MEFs but were hyperactive in IKKalpha KO MEFs. More surprisingly, NF
      kappaB responses were near normal in TRAF2 and TRAF5 double-KO MEFs, IKKgamma KO
      MEFs, TAB2 KO MEFs, and IRAK4 KO MEFs but were highly deficient in TRAF6 KO MEFs
      and IRAK1 KO HEK293 cells. Consistent with the importance of TRAF6, LMP1-induced
      NF-kappaB activation in HEK293 cells was inhibited by expression of dominant
      negative TAB2 and Ubc13 alleles. These data extend a role for IKKalpha in IKKbeta
      regulation, identify an unusual IKKbeta-dependent and IKKgamma-independent NF
      kappaB activation, and indicate that IRAK1 and TRAF6 are essential for LMP1
      induced NF-kappaB activation.

PMID- 14673103
TI  - Arabidopsis CHL27, located in both envelope and thylakoid membranes, is required
      for the synthesis of protochlorophyllide.
AB  - CHL27, the Arabidopsis homologue to Chlamydomonas Crd1, a plastid-localized
      putative diiron protein, is required for the synthesis of protochlorophyllide and
      therefore is a candidate subunit of the aerobic cyclase in chlorophyll
      biosynthesis. delta-Aminolevulinic acid-fed antisense Arabidopsis plants with
      reduced amounts of Crd1/CHL27 accumulate Mg-protoporphyrin IX monomethyl ester,
      the substrate of the cyclase reaction. Mutant plants have chlorotic leaves with
      reduced abundance of all chlorophyll proteins. Fractionation of Arabidopsis
      chloroplast membranes shows that Crd1/CHL27 is equally distributed on a membrane
      weight basis in the thylakoid and inner-envelope membranes.

PMID- 14673104
TI  - Intracellular localization of a group II chaperonin indicates a membrane-related
      function.
AB  - Chaperonins are protein complexes that are believed to function as part of a
      protein folding system in the cytoplasm of the cell. We observed, however, that
      the group II chaperonins known as rosettasomes in the hyperthermophilic archaeon
      Sulfolobus shibatae, are not cytoplasmic but membrane associated. This
      association was observed in cultures grown at 60 degrees C and 76 degrees C or
      heat-shocked at 85 degrees C by using immunofluorescence microscopy and in thick
      sections of rapidly frozen cells grown at 76 degrees C by using immunogold
      electron microscopy. We observed that increased abundance of rosettasomes after
      heat shock correlated with decreased membrane permeability at lethal temperature
      (92 degrees C). This change in permeability was not seen in cells heat-shocked in
      the presence of the amino acid analogue azetidine 2-carboxylic acid, indicating
      functional protein synthesis influences permeability. Azetidine experiments also
      indicated that observed heat-induced changes in lipid composition in S. shibatae
      could not account for changes in membrane permeability. Rosettasomes purified
      from cultures grown at 60 degrees C and 76 degrees C or heat-shocked at 85
      degrees C bind to liposomes made from either the bipolar tetraether lipids of
      Sulfolobus or a variety of artificial lipid mixtures. The presence of
      rosettasomes did not significantly change the transition temperature of
      liposomes, as indicated by differential scanning calorimetry, or the proton
      permeability of liposomes, as indicated by pyranine fluorescence. We propose that
      these group II chaperonins function as a structural element in the natural
      membrane based on their intracellular location, the correlation between their
      functional abundance and membrane permeability, and their potential distribution
      on the membrane surface.

PMID- 14673105
TI  - Genome evolution reveals biochemical networks and functional modules.
AB  - The analysis of completely sequenced genomes uncovers an astonishing variability
      between species in terms of gene content and order. During genome history, the
      genes are frequently rear-ranged, duplicated, lost, or transferred horizontally
      between genomes. These events appear to be stochastic, yet they are under
      selective constraints resulting from the functional interactions between genes.
      These genomic constraints form the basis for a variety of techniques that employ
      systematic genome comparisons to predict functional associations among genes. The
      most powerful techniques to date are based on conserved gene neighborhood, gene
      fusion events, and common phylogenetic distributions of gene families. Here we
      show that these techniques, if integrated quantitatively and applied to a
      sufficiently large number of genomes, have reached a resolution which allows the
      characterization of function at a higher level than that of the individual gene:
      global modularity becomes detectable in a functional protein network. In
      Escherichia coli, the predicted modules can be bench-marked by comparison to
      known metabolic pathways. We found as many as 74% of the known metabolic enzymes
      clustering together in modules, with an average pathway specificity of at least
      84%. The modules extend beyond metabolism, and have led to hundreds of reliable
      functional predictions both at the protein and pathway level. The results
      indicate that modularity in protein networks is intrinsically encoded in present
      day genomes.

PMID- 14673106
TI  - Molecular determinants of Ca(2+)/calmodulin-dependent regulation of Ca(v)2.1
      channels.
AB  - Ca2+-dependent facilitation and inactivation (CDF and CDI) of Cav2.1 channels
      modulate presynaptic P/Q-type Ca2+ currents and contribute to activity-dependent
      synaptic plasticity. This dual feedback regulation by Ca2+ involves calmodulin
      (CaM) binding to the alpha1 subunit (alpha12.1). The molecular determinants for
      Ca2+-dependent modulation of Cav2.1 channels reside in CaM and in two CaM-binding
      sites in the C-terminal domain of alpha12.1, the CaM-binding domain (CBD) and the
      IQ-like domain. In transfected tsA-201 cells, CDF and CDI were both reduced by
      deletion of CBD. In contrast, alanine substitution of the first two residues of
      the IQ-like domain (IM-AA) completely prevented CDF but had little effect on CDI,
      and glutamate substitutions (IM-EE) greatly accelerated voltage-dependent
      inactivation but did not prevent CDI. Mutational analyses of the Ca2+ binding
      sites of CaM showed that both the N- and C-terminal lobes of CaM were required
      for full development of facilitation, but only the N-terminal lobe was essential
      for CDI. In biochemical assays, CaM12 and CaM34 were unable to bind CBD, whereas
      CaM34 but not CaM12 retained Ca2+-dependent binding to the IQ-like domain. These
      findings support a model in which Ca2+ binding to the C-terminal EF-hands of
      preassociated CaM initiates CDF via interaction with the IQ-like domain. Further
      Ca2+ binding to the N-terminal EF-hands promotes secondary CaM interactions with
      CBD, which enhance facilitation and cause a conformational change that initiates
      CDI. This multifaceted mechanism allows positive regulation of Cav2.1 in response
      to local Ca2+ increases (CDF) and negative regulation during more global Ca2+
      increases (CDI).

PMID- 14673107
TI  - Contribution of the H63D mutation in HFE to murine hereditary hemochromatosis.
AB  - Hereditary hemochromatosis (HH) is an autosomal recessive disease characterized
      by iron accumulation in several organs, followed by organ damage and failure. The
      C282Y mutation in the HFE gene explains 80-90% of all diagnosed cases of HH in
      populations of northwestern European ancestry. Targeted disruption of the mouse
      Hfe gene (or introduction of the murine mutation analogous to the C282Y human
      mutation) produces a murine model of HH. Another mutation in the HFE gene, H63D,
      is more prevalent than C282Y. However, the physiological consequences of the H63D
      mutation (as well as C282Y/H63D compound heterozygosity) on iron homeostasis are
      less well established. To evaluate the phenotypic consequences of the C282Y/H63D
      and H63D/H63D genotypes, we produced H67D (corresponding to H63D in humans) and
      C294Y (corresponding to C282Y in humans) knock-in mice. H67D homozygous mice,
      C294Y homozygous mice, and H67D/C294Y compound heterozygous mice each
      demonstrated hepatic iron loading. Even on a standard diet, by 10 weeks of age,
      hepatic iron levels in mice of these three genotypes were significantly higher
      than those of wild-type littermates. The relative severity of hepatic iron
      loading was C294Y/C294Y > C294Y/H67D > H67D/H67D. We conclude that the H67D
      allele, when homozygous or combined with a more consequential mutation like
      C294Y, leads to hepatic iron loading. These observations indicate that the H67D
      mutation leads to partial loss of Hfe function and can contribute to murine HH.

PMID- 14673108
TI  - Ebola virus-like particles protect from lethal Ebola virus infection.
AB  - The filovirus Ebola causes hemorrhagic fever with 70-80% human mortality. High
      case-fatality rates, as well as known aerosol infectivity, make Ebola virus a
      potential global health threat and possible biological warfare agent. Development
      of an effective vaccine for use in natural outbreaks, response to biological
      attack, and protection of laboratory workers is a higher national priority than
      ever before. Coexpression of the Ebola virus glycoprotein (GP) and matrix protein
      (VP40) in mammalian cells results in spontaneous production and release of virus
      like particles (VLPs) that resemble the distinctively filamentous infectious
      virions. VLPs have been tested and found efficacious as vaccines for several
      viruses, including papillomavirus, HIV, parvovirus, and rotavirus. Herein, we
      report that Ebola VLPs (eVLPs) were immunogenic in vitro as eVLPs matured and
      activated mouse bone marrow-derived dendritic cells, assessed by increases in
      cell-surface markers CD40, CD80, CD86, and MHC class I and II and secretion of IL
      6, IL-10, macrophage inflammatory protein (MIP)-1alpha, and tumor necrosis factor
      alpha by the dendritic cells. Further, vaccinating mice with eVLPs activated CD4+
      and CD8+ T cells, as well as CD19+ B cells. After vaccination with eVLPs, mice
      developed high titers of Ebola virus-specific antibodies, including neutralizing
      antibodies. Importantly, mice vaccinated with eVLPs were 100% protected from an
      otherwise lethal Ebola virus inoculation. Together, our data suggest that eVLPs
      represent a promising vaccine candidate for protection against Ebola virus
      infections and a much needed tool to examine the genesis and nature of immune
      responses to Ebola virus.

PMID- 14673109
TI  - Enhanced levels of lambda Red-mediated recombinants in mismatch repair mutants.
AB  - Homologous recombination can be used to generate recombinants on episomes or
      directly on the Escherichia coli chromosome with PCR products or synthetic single
      stranded DNA (ssDNA) oligonucleotides (oligos). Such recombination is possible
      because bacteriophage lambda-encoded functions, called Red, efficiently recombine
      linear DNA with homologies as short as 20-70 bases. This technology, termed
      recombineering, provides ways to modify genes and segments of the chromosome as
      well as to study homologous recombination mechanisms. The Red Beta function,
      which binds and anneals ssDNA to complementary ssDNA, is able to recombine 70
      base oligos with the chromosome. In E. coli, methyl-directed mismatch repair
      (MMR) can affect these ssDNA recombination events by eliminating the recombinant
      allele and restoring the original sequence. In so doing, MMR can reduce the
      apparent recombination frequency by >100-fold. In the absence of MMR, Red
      mediated oligo recombination can incorporate a single base change into the
      chromosome in an unprecedented 25% of cells surviving electroporation. Our
      results show that Beta is the only bacteriophage function required for this level
      of recombination and suggest that Beta directs the ssDNA to the replication fork
      as it passes the target sequence.

PMID- 14673110
TI  - Protection of Cftr knockout mice from acute lung infection by a helper-dependent
      adenoviral vector expressing Cftr in airway epithelia.
AB  - We developed a helper-dependent adenoviral vector for cystic fibrosis lung gene
      therapy. The vector expresses cystic fibrosis transmembrane conductance regulator
      (Cftr) using control elements from cytokeratin 18. The vector expressed properly
      localized CFTR in cultured cells and in the airway epithelia of mice. Cftr RNA
      and protein were present in whole lung and bronchioles, respectively, for 28 days
      after a vector dose. Acute inflammation was minimal to moderate. To test the
      therapeutic potential of the vector, we challenged mice with a clinical strain of
      Burkholderia cepacia complex (Bcc). Cftr knockout mice (but not Cftr+/+
      littermates) challenged with Bcc developed severe lung histopathology and had
      high lung bacteria counts. Cftr knockout mice receiving gene therapy 7 days
      before Bcc challenge had less severe histopathology, and the number of lung
      bacteria was reduced to the level seen in Cftr+/+ littermates. These data suggest
      that gene therapy could benefit cystic fibrosis patients by reducing
      susceptibility to opportunistic pathogens.

PMID- 14673111
TI  - Symmetry considerations and development of pinwheels in visual maps.
AB  - Neurons in the visual cortex respond best to rod-like stimuli of given
      orientation. While the preferred orientation varies continuously across most of
      the cortex, there are prominent pinwheel centers around which all orientations
      are present. Oriented segments abound in natural images and tend to be collinear;
      neurons are also more likely to be connected if their preferred orientations are
      aligned to their topographic separation. These are indications of a reduced
      symmetry requiring joint rotations of both orientation preference and the
      underlying topography. We verify that this requirement extends to cortical maps
      of monkey and cat by direct statistical analysis. Furthermore, analytical
      arguments and numerical studies indicate that pinwheels are generically stable in
      evolving field models that couple orientation and topography.

PMID- 14673112
TI  - Probing protein oligomerization in living cells with fluorescence fluctuation
      spectroscopy.
AB  - Fluorescence fluctuation spectroscopy provides information about protein
      interactions in the intercellular environment from naturally occurring
      equilibrium fluctuations. We determine the molecular brightness of fluorescent
      proteins from the fluctuations by analyzing the photon counting histogram (PCH)
      or its moments and demonstrate the use of molecular brightness in probing the
      oligomerization state of proteins. We report fluorescence fluctuation
      measurements of enhanced GFP (EGFP) in cells up to concentrations of 10 microM by
      using an improved PCH theory. The molecular brightness of EGFP is constant in the
      concentration range studied. The brightness of a tandem EGFP construct, which
      carries two fluorophores, increases by a factor of two compared with EGFP alone,
      demonstrating the sensitivity of molecular brightness as a probe for protein
      complex formation. Oligomerization of nuclear receptors plays a crucial role in
      the regulation of gene expression. We probe the oligomerization state of the
      testicular receptor 4 and the ligand-binding domains of retinoid X receptor and
      retinoic acid receptor by observing molecular brightness changes as a function of
      protein concentration. The large concentration range accessible by experiment
      allows us to perform titration experiments on EGFP fusion proteins. An increase
      in the molecular brightness with protein concentration indicates the formation of
      homocomplexes. We observe the formation of homodimers of retinoid X receptor
      ligand binding domain upon addition of ligand. Resolving protein interactions in
      a cell is an important step in understanding cellular function on a molecular
      level. Brightness analysis promises to develop into an important tool for
      determining protein complex formation in cells.

PMID- 14673113
TI  - A general strategy for target-promoted alkylation in biological systems.
AB  - Selective alkylation of a chosen sequence of DNA typically relies on ligand
      directed delivery of a compound that expresses an intrinsic reactivity. A
      significant and biologically relevant enhancement in specificity is theoretically
      possible if such an intrinsic reactivity could be replaced by a latent activity
      induced solely by the target of interest, but examples of this are rare and not
      easily emulated. A simple strategy for target-promoted alkylation is now
      illustrated by an intramolecular adduct formed by an oligonucleotide-quinone
      methide conjugate. This adduct persists in the absence of a complementary
      sequence of DNA for at least 8 days, yet remarkably is able to alkylate target
      DNA upon duplex hybridization. Neither formation of the intramolecular self
      adduct nor transfer of the quinone methide to its target is significantly
      quenched by 450-fold excess 2-mercaptoethanol. Similarly, noncomplementary DNA is
      neither subject to alkylation by the self-adduct nor able to effect its
      consumption. Reversible trapping of the nascent quinone methide through an
      intramolecular reaction thus appears efficient enough to inhibit competing
      intermolecular reaction. Only complementary base pairing induces a conformational
      change necessary to promote intermolecular transfer of the quinone methide.
      Generalization of this approach based on reversible intramolecular trapping of a
      reactive intermediate by a ligand with multiple recognition subdomains has the
      potential for wide-ranging applications in targeting nucleic acids and proteins.

PMID- 14673114
TI  - Host defense reinforces host-parasite cospeciation.
AB  - Cospeciation occurs when interacting groups, such as hosts and parasites,
      speciate in tandem, generating congruent phylogenies. Cospeciation can be a
      neutral process in which parasites speciate merely because they are isolated on
      diverging host islands. Adaptive evolution may also play a role, but this has
      seldom been tested. We explored the adaptive basis of cospeciation by using a
      model system consisting of feather lice (Columbicola) and their pigeon and dove
      hosts (Columbiformes). We reconstructed phylogenies for both groups by using
      nuclear and mitochondrial DNA sequences. Both phylogenies were well resolved and
      well supported. Comparing these phylogenies revealed significant cospeciation and
      correlated evolution of host and parasite body size. The match in body size
      suggested that adaptive constraints limit the range of hosts lice can use. We
      tested this hypothesis by transferring lice among hosts of different sizes to
      simulate host switches. The results of these experiments showed that lice cannot
      establish viable populations on novel hosts that differ in size from the native
      host. To determine why size matters, we measured three components of louse
      fitness: attachment, feeding, and escape from host defense (preening). Lice could
      remain attached to, and feed on, hosts varying in size by an order of magnitude.
      However, they could not escape from preening on novel hosts that differed in size
      from the native host. Overall, our results suggest that host defense reinforces
      cospeciation in birds and feather lice by preventing lice from switching between
      hosts of different sizes.

PMID- 14673115
TI  - In vivo oligomerization and raft localization of Ebola virus protein VP40 during
      vesicular budding.
AB  - The matrix protein VP40 plays a critical role in Ebola virus assembly and
      budding, a process that utilizes specialized membrane domains known as lipid
      rafts. Previous studies with purified protein suggest a role for oligomerization
      of VP40 in this process. Here, we demonstrate VP40 oligomers in lipid rafts of
      mammalian cells, virus-like particles, and in the authentic Ebola virus. By
      mutagenesis, we identify several critical C-terminal sequences that regulate
      oligomerization at the plasma membrane, association with detergent-resistant
      membranes, and vesicular release of VP40, directly linking these phenomena.
      Furthermore, we demonstrate the active recruitment of TSG101 into lipid rafts by
      VP40. We also report the successful application of the biarsenic fluorophore,
      FlAsH, combined with a tetracysteine tag for imaging of Ebola VP40 in live cells.

PMID- 14673116
TI  - Domain movements of HAP2 in the cap-filament complex formation and growth process
      of the bacterial flagellum.
AB  - The cap at the growing end of the bacterial flagellum is essential for its
      growth, remaining stably attached while permitting the insertion of flagellin
      transported from the cytoplasm through the narrow central channel. We analyzed
      the structure of the isolated cap in its frozen hydrated state by electron
      cryomicroscopy. The 3D density map now shows detailed features of domains and
      their connections, giving reliable volumes and masses, making assignment of the
      domains to the amino acid sequence possible. A model of the cap-filament complex
      built with an atomic model of the filament allows a quantitative analysis of the
      cap domain movements on cap binding and rotation that promotes the efficient self
      assembly of flagellin during the filament growth process.

PMID- 14673117
TI  - Visualizing lipid structure and raft domains in living cells with two-photon
      microscopy.
AB  - The lateral organization of cellular membranes is formed by the clustering of
      specific lipids, such as cholesterol and sphingolipids, into highly condensed
      domains (termed lipid rafts). Hence such domains are distinct from the remaining
      membrane by their lipid structure (liquid-ordered vs. -disordered domains). Here,
      we directly visualize membrane lipid structure of living cells by using two
      photon microscopy. In macrophages, liquid-ordered domains are particularly
      enriched on membrane protrusions (filopodia), adhesion points and cell-cell
      contacts and cover 10-15% of the cell surface at 37 degrees C. By deconvoluting
      the images, we demonstrate the existence of phase separation in vivo. We compare
      the properties of microscopically visible domains (<1 microm2), with those of
      isolated detergent-resistant membranes and provide evidence that membrane
      coverage by lipid rafts and their fluidity are principally governed by
      cholesterol content, thereby providing strong support for the lipid raft
      hypothesis.

PMID- 14673118
TI  - Thioredoxin-linked processes in cyanobacteria are as numerous as in chloroplasts,
      but targets are different.
AB  - Light-dependent regulation of a growing number of chloroplast enzymatic
      activities has been found to occur through the reversible reduction of intra- or
      intermolecular disulphides by thioredoxins. In cyanobacteria, despite their
      similarity to chloroplasts, no proteins have hitherto been shown to interact with
      thioredoxins, and the role of the cyanobacterial ferredoxin/thioredoxin system
      has remained obscure. By using an immobilized cysteine 35-to-serine site-directed
      mutant of the Synechocystis sp. PCC 6803 thioredoxin TrxA as bait, we screened
      the Synechocystis cytosolic and peripheral membrane protein complements for
      proteins interacting with TrxA. The covalent bond between the isolated target
      proteins and mutated TrxA was confirmed by nonreducing/reducing two-dimensional
      SDS/PAGE. Thus, we have identified 18 cytosolic proteins and 8 membrane
      associated proteins as candidate thioredoxin substrates. Twenty of these proteins
      have not previously been associated with thioredoxin-mediated regulation.
      Phosphoglucomutase, one of the previously uncharacterized thioredoxin-linked
      enzymes, has not earlier been considered a target for metabolic control through
      disulphide reduction. In this article, we show that phosphoglucomutase is
      inhibited under oxidizing conditions and activated by DTT and reduced wild-type
      TrxA in vitro. The results imply that thioredoxin-mediated redox regulation is as
      extensive in cyanobacteria as in chloroplasts but that the subjects of regulation
      are largely different.

PMID- 14673120
TI  - Do the arts and humanities have a place in occupational medicine?

PMID- 14673122
TI  - The ailing leader--a suitable case for occupational medicine?

PMID- 14673119
TI  - Induction of colitis by a CD4+ T cell clone specific for a bacterial epitope.
AB  - It is now well established that the intestinal flora plays an important role in
      the pathogenesis of inflammatory bowel disease (IBD). However, whether bacteria
      serve as the sole target of the immune response in this process or whether they
      act indirectly by triggering an anti-self response is still unclear. We have
      previously shown that specific pathogen-free IL-10-deficient (IL-10 KO) mice
      develop a T helper (Th1)-cytokine associated colitis after experimental infection
      with Helicobacter hepaticus. We here show that H. hepaticus Ag (SHelAg)-specific
      CD4+ Th1 clones transfer disease to H. hepaticus-infected T cell-deficient RAG KO
      hosts. Importantly, uninfected recipients of the SHelAg-specific clones did not
      develop intestinal inflammation, and a control Schistosoma mansoni-specific Th1
      clone did not induce colitis upon transfer to infected RAG KO mice. The disease
      inducing T cell clones recognized antigen(s) (Ag) specifically expressed by
      certain Helicobacter species as they responded when stimulated in vitro with H.
      hepaticus and Helicobacter typhlonius Ag, but not when cultured with Ag
      preparations from Helicobacter pylori, various non-helicobacter bacteria, or with
      cecal bacterial lysate from uninfected mice. Characterization of the Ag
      specificity of one of the clones showed that it reacts uniquely with a 15-mer
      peptide epitope on the flagellar hook protein (FlgE) of H. hepaticus presented by
      I-Ab. Together, our results demonstrate that colitis can be induced by clonal T
      cell populations that are highly specific for target Ag on intestinal bacteria,
      suggesting that an aberrant T cell response directed against gut flora is
      sufficient to trigger IBD.

PMID- 14673123
TI  - Thackrah's grave.

PMID- 14673124
TI  - Dr Thomas Ownsworth Garland, 1903-1993: New Zealand's pioneer in occupational
      medicine.

PMID- 14673125
TI  - Health and safety implications of injury in professional rugby league football.
AB  - BACKGROUND: Professional sport is characterized by high injury rates but is also
      covered by health and safety legislation. AIM: To examine the incidence of injury
      in professional rugby league as defined by the Reporting of Diseases and
      Dangerous Occurrences Regulations 1995 (RIDDOR 95). METHODS: All injuries
      received during playing and training to both first-team and 'academy' (<19 years
      old) players during two playing seasons at one professional club were recorded.
      The length of time a player was unable to take part in full training and playing
      was used as a measure of severity. Injuries were classified into minor injuries
      (0-3 days), over 3 day injuries or major injuries, in which the final two
      categories corresponded with RIDDOR 95. RESULTS: Thirty-two per cent (95%
      confidence interval=26-39%) of all injuries received satisfied the RIDDOR 95
      criteria. The overall injury rate was 8.5 per 1000 h (7.2-9.9) for the first team
      and 4.1 per 1000 h (3.2-5.4) for the academy team. During match play the first
      team injury rate was 157.7 per 1000 h (133.5-185.1) and 67.7 (51-81.1) for the
      academy team. Training injury rates were lower, at 0.5 per 1000 h (0.2-1.0) and
      0.3 per 1000 h (0.1-0.8), respectively. CONCLUSION: The injury rate for
      professional rugby league is much higher than reported in other high-risk
      occupations such as mining and quarrying. The large differences in injury rates
      between first and academy teams have implications for young players likely to
      progress to first-team status.

PMID- 14673126
TI  - Screening for high-risk and elevated alcohol consumption in day and shift workers
      by use of the AUDIT and CDT.
AB  - BACKGROUND: Alcohol consumption levels and drinking patterns have been reported
      to vary between day and shift workers, although the results have been
      conflicting. Previous results indicate that questions about alcohol habits may be
      asked in the workplace. However, no studies have evaluated the Alcohol Use
      Disorders Identification Test (AUDIT) or the alcohol biomarker carbohydrate
      deficient transferrin (CDT) in serum for this purpose. AIM: To investigate, in
      conjunction with routine health examinations, whether there is any difference
      between permanent day and shift workers in high-risk alcohol consumption,
      according to the AUDIT and CDT. Gamma-glutamyl transferase (GGT) in serum was
      included mainly as a comparison test. METHODS: The employees who attended for a
      regular health examination during the study period were offered voluntary alcohol
      screening with the AUDIT and CDT. RESULTS: Altogether, 990 employees (day, two
      shift, and three-shift workers) participated in the study, 194 (20%) of whom
      screened positive with the AUDIT and/or CDT. There were no significant
      differences in the screening results between day and shift workers, whereas
      significantly fewer of the two-shift workers (odds ratio=0.5, 95% confidence
      interval=0.3-0.9) screened positive with CDT. CONCLUSIONS: The present findings
      on employees who attended for regular health examinations suggest that shift
      workers did not show a higher level of risky alcohol consumption than day
      workers, according to the results with the AUDIT, CDT and GGT. On the contrary,
      the two-shift workers appeared to drink significantly less.

PMID- 14673127
TI  - Increased risk of asthma among Finnish construction workers.
AB  - AIM: To determine the risk of asthma among 7891 Finnish construction workers in
      the Pirkanmaa Region of southern Finland. METHOD: Retrospective cohort study of
      hospital records of the Tampere University Hospital. A population of Pirkanmaa
      paper mill workers (n=2686) and the Pirkanmaa working age population (n=252,500)
      served as reference populations. RESULTS: There were 147 new cases of asthma
      among the construction workers in 1991-1995. The annual rate was 37 per 10,000
      workers and the odds ratio was 2.1 [95% confidence interval (CI)=1.2-3.6] for the
      women and 1.8 (95% CI=1.5-2.2) for the men when compared with the general working
      age population. In general, the risk of asthma among the paper mill workers did
      not differ from the risk of asthma among the general working age population. The
      construction workers had an increased risk for asthma, although the number of
      reported cases of occupational asthma was lower for the construction workers than
      for the paper mill workers or for the working population. CONCLUSION:
      Construction work, especially dusty tasks, was associated with an elevated risk
      of asthma. Thus the effect of exposure to irritant agents may have a role in the
      development of asthma among construction workers. For the most part, these cases
      of asthma do not meet the criteria for occupational asthma because the specified
      causal agent can not be defined. The aetiologic agents and mechanisms of asthma
      in construction work should be clarified for preventive measures.

PMID- 14673132
TI  - Agonist-activated glucocorticoid receptor inhibits binding of heat shock factor 1
      to the heat shock protein 70 promoter in vivo.
AB  - We have previously shown that activation of glucocorticoid receptor (GR)
      signaling in stressed cells will cause inhibition of the heat shock response as
      mediated by heat shock transcription factor 1 (HSF1). In that work, a full-length
      human heat shock protein 70 (Hsp70) promoter was used to measure HSF1
      transactivity, and the data suggested inhibition of HSF1 through the
      transactivation or transrepressive properties of GR. Here, we show that the
      inhibitory effect of glucocorticoid agonist (dexamethasone) upon Hsp70 promoter
      activity is rapid, occurring within 1 h of hormone addition. Moreover, addition
      of hormone during the first hour of recovery from stress was sufficient to
      inhibit HSF1. Thus, dexamethasone is able to rapidly reverse HSF1 transactivity,
      suggesting a transrepressive mode of action for GR. Yet, GR transrepression of
      HSF1 by analysis of putative negative glucocorticoid response elements in the
      Hsp70 promoter was not found. To further investigate the in vivo nature of this
      fast-acting mechanism, we used the chromatin immunoprecipitation assay with
      primers specific to the human Hsp70 promoter. Dexamethasone inhibited HSF1
      binding at the Hsp70 promoter in response to heat or chemical shock (sodium
      arsenite). Moreover, dexamethasone also blocked promoter binding by a
      constitutively active mutant of HSF1 (hHSF1-E189) expressed under nonstress
      conditions. In all cases, inhibition of HSF1 recruitment to the promoter by
      dexamethasone was blocked by the GR antagonist RU486, a result that was
      consistent with promoter activity based on chloramphenicol acetyl transferase
      gene expression. The ability of dexamethasone to prevent HSF1 recruitment to the
      promoter was fast acting (occurring in as little as 15 min), and the hormone also
      caused release of HSF1 already bound to the promoter. Although these results
      suggest GR can effectively prevent HSF1 binding to Hsp promoters, fractionation
      and Western blot experiments showed that stress-activated HSF1 was not released
      from the nucleus in response to hormone. Thus, this effect of dexamethasone is
      either specific to the Hsp70 promoter or causes shunting of HSF1 to other high
      affinity nuclear sites. These observations provide evidence of a novel mechanism
      for attenuation of the heat shock response by glucocorticoids: prevention or
      reversal of HSF1 recruitment to Hsp promoters through the rapid actions of GR.

PMID- 14673133
TI  - Assessment of the role of activator protein-1 on transcription of the mouse
      steroidogenic acute regulatory protein gene.
AB  - cAMP-dependent mechanisms regulate the steroidogenic acute regulatory (StAR)
      protein even though its promoter lacks a consensus cAMP response-element (CRE,
      TGACGTCA). Transcriptional regulation of the StAR gene has been demonstrated to
      involve combinations of DNA sequences that provide recognition motifs for
      sequence-specific transcription factors. We recently identified and characterized
      three canonical 5'-CRE half-sites within the cAMP-responsive region (-151/-1 bp)
      of the mouse StAR gene. Among these CRE elements, the CRE2 half-site is analogous
      (TGACTGA) to an activator protein-1 (AP-1) sequence [TGA(C/G)TCA]; therefore, the
      role of the AP-1 transcription factor was explored in StAR gene transcription.
      Mutation in the AP-1 element demonstrated an approximately 50% decrease in StAR
      reporter activity. Using EMSA, oligonucleotide probes containing an AP-1 binding
      site were found to specifically bind to nuclear proteins obtained from mouse MA
      10 Leydig and Y-1 adrenocortical tumor cells. The integrity of the sequence
      specific AP-1 element in StAR gene transcription was assessed using the AP-1
      family members, Fos (c-Fos, Fra-1, Fra-2, and Fos B) and Jun (c-Jun, Jun B, and
      Jun D), which demonstrated the involvement of Fos and Jun in StAR gene
      transcription to varying degrees. Disruption of the AP-1 binding site reversed
      the transcriptional responses seen with Fos and Jun. EMSA studies utilizing
      antibodies specific to Fos and Jun demonstrated the involvement of several AP-1
      family proteins. Functional assessment of Fos and Jun was further demonstrated by
      transfecting antisense c-Fos, Fra-1, and dominant negative forms of Fos (A-Fos)
      and c-Jun (TAM-67) into MA-10 cells, which significantly (P < 0.01) repressed
      transcription of the StAR gene. Mutation of the AP-1 site in combination with
      mutations in other cis-elements resulted in a further decrease of StAR promoter
      activity, demonstrating a functional cooperation between these factors. Mammalian
      two-hybrid assays revealed high-affinity protein-protein interactions between c
      Fos and c-Jun with steroidogenic factor 1, GATA-4, and CCAAT/enhancer binding
      protein-beta. These findings demonstrate that Fos and Jun can bind to the TGACTGA
      element in the StAR promoter and provide novel insights into the mechanisms
      regulating StAR gene transcription.

PMID- 14673134
TI  - Mutations of the anti-mullerian hormone gene in patients with persistent
      mullerian duct syndrome: biosynthesis, secretion, and processing of the abnormal
      proteins and analysis using a three-dimensional model.
AB  - Anti-Mullerian hormone (AMH), a TGF-beta family member, determines whether an
      individual develops a uterus and Fallopian tubes. Mutations in the AMH gene lead
      to persistent Mullerian duct syndrome in males. The wild-type human AMH protein
      is synthesized as a disulfide-linked dimer of two identical 70-kDa polypeptides,
      which undergoes proteolytic processing to generate a 110-kDa N-terminal dimer and
      a bioactive 25-kDa TGF-beta-like C-terminal dimer. We have studied the
      biosynthesis and secretion of wild-type AMH and of seven persistent Mullerian
      duct syndrome proteins, containing mutations in either the N- or C-terminal
      domain. Mutant proteins lacking the C-terminal domain are secreted more rapidly
      than full-length AMH, whereas single amino acid changes in both domains can have
      profound effects on protein stability and folding. The addition of a cysteine in
      an N-terminal domain mutant, R194C, prevents proper folding, whereas the
      elimination of the cysteine involved in forming the interchain disulfide bond, in
      a C-terminal domain mutant, C525Y, leads to a truncation at the C terminus. A
      molecular model of the AMH C-terminal domain provides insights into how some
      mutations could affect biosynthesis and function.

PMID- 14673135
TI  - Enhancement of glucocorticoid receptor-mediated gene expression by constitutively
      active heat shock factor 1.
AB  - To further define the role of heat shock factor 1 (HSF1) in the stress
      potentiation of glucocorticoid receptor (GR) activity, we placed a constitutively
      active mutant of human HSF1 (hHSF1-E189) under the control of a doxycycline (DOX)
      inducible vector. In mouse L929 cells, DOX-induced expression of hHSF1-E189
      correlated with in vivo occupancy of the human heat shock protein 70 (hHsp70)
      promoter (chromatin-immunoprecipitation assay) and with increased activity under
      nonstress conditions at the hHsp70 promoter controlling expression of
      chloramphenicol acetyl transferase (CAT) (p2500-CAT). Comparison of hHSF1-E189
      against stress-activated, endogenous HSF1 for DNA-binding, p2500-CAT, and Hsp70
      protein expression activities showed the mutant factor to have lower, but clearly
      detectable, activities as compared with wild-type factor. Thus, the hHSF1-E189
      mutant is capable of replicating these key functions of endogenous HSF1, albeit
      at reduced levels. To assess the involvement of hHSF1-E189 in GR activity, DOX
      induced expression of hHSF1-E189 was performed in L929 cells expressing the
      minimal pGRE(2)E1B-CAT reporter. hHSF1-E189 protein expression in these cells was
      maximal at 24 h of DOX and remained constant up to 72 h. hHSF1-E189 expressed
      under these conditions was found both in the cytosolic and nuclear compartments,
      in a state capable of binding DNA. More importantly, GR activity at the
      pGRE(2)E1B-CAT promoter was found to increase after DOX-induced expression of
      hHSF1-E189. The potentiation of GR by hHSF1-E189 occurred at saturating
      concentrations of hormone and was dependent on at least 48 h of hHSF1-E189 up
      regulation, suggesting that time was needed for an HSF1-induced factor to
      accumulate to a threshold level. Initial efforts to characterize how hHSF1-E189
      controls GR signaling showed that it does not occur through alterations of GR
      protein levels or changes in GR hormone binding capacity. In summary, our
      observations provide the first molecular evidence for the existence of HSF1
      regulated genes that serve to elevate the response of steroid receptors under
      stress conditions.

PMID- 14673136
TI  - Urban renewal in the nucleus: is protein turnover by proteasomes absolutely
      required for nuclear receptor-regulated transcription?
AB  - The importance of the ubiquitin proteasome pathway in higher eukaryotes has been
      well established in cell cycle regulation, signal transduction, and cell
      differentiation, but has only recently been linked to nuclear hormone receptor
      regulated gene transcription. Characterization of a number of ubiquitin
      proteasome pathway enzymes as coactivators and observations that several nuclear
      receptors are ubiquitinated and degraded in the course of their nuclear
      activities provide evidence that ubiquitin proteasome-mediated protein
      degradation plays an integral role in eukaryotic transcription. In addition to
      receptors, studies have revealed that coactivators are ubiquitinated and degraded
      via the proteasome. The notion that the ubiquitin proteasome pathway is involved
      in gene transcription is further strengthened by the fact that ubiquitin
      proteasome pathway enzymes are recruited to the promoters of target genes and
      that proteasome-dependent degradation of nuclear receptors is required for
      efficient transcriptional activity. These findings suggest that protein
      degradation is coupled with nuclear receptor coactivation activity. It is
      possible that the ubiquitin proteasome pathway modulates transcription by
      promoting remodeling and turnover of the nuclear receptor-transcription complex.
      In this review, we discus the possible role of the ubiquitin proteasome pathway
      in nuclear hormone receptor-regulated gene transcription.

PMID- 14673137
TI  - Binding of AP-2 and ETS-domain family members is associated with enhancer
      activity in the hypersensitive site III region of the human growth
      hormone/chorionic somatomammotropin locus.
AB  - The human GH gene family is specifically expressed in somatotrophs of the
      anterior pituitary and placental syncytiotrophoblast. Two nuclease-hypersensitive
      sites, HS III and HS V, are associated with a region of chromatin located 28 and
      30 kb upstream of the pituitary GH gene transcription initiation site (+1) in
      both pituitary and placenta nuclei. A role for this region in pituitary GH gene
      expression has been reported, but the potential relevance to placental gene
      expression has not been determined. Deletion analysis of a 5.2-kb region
      (nucleotides - 27,568/-32,746) containing HS III to V-related sequences localized
      significant enhancer activity to a 574-bp HS III fragment (nucleotides -27,676/
      28,249) in multiple transfected cell lines. Four nuclease-protected regions
      [footprints (FP) 1-4] were identified in the 574-bp fragment. FP2 and FP3 were
      detected with placenta cell nuclear protein, whereas FP1 and FP4 were observed
      with placental and nonplacental cell nuclear extract. Disruption of FP1 had no
      effect on heterologous promoter activity in transfected pituitary and placental
      cells, whereas loss of FP2 and FP3 resulted in modest increases in placental
      cells, reflecting the presence of repressor activity associated with these
      regions in vitro. In contrast, disruption of the FP4 region by mutation or
      deletion significantly reduced enhancer activity. As a result, 30-fold enhancer
      activity was localized to a 41-bp region in transfected placental tumor cells.
      Binding of candidate proteins, activator protein (AP)-2 (FP3) and Elk-1 (FP4),
      was confirmed using competition assays with specific oligonucleotides and
      antibodies. Moreover, these factors were associated with the hyperacetylated HS
      III region in human pituitary [activator protein 2 (AP-2) and Elk-1] and term
      placenta (AP-2) chromatin. These data implicate AP-2 and ETS-domain family
      members in the regulation of the GH/CS locus and raise the possibility that
      different complexes form in the HS III region in placenta and pituitary cells.

PMID- 14673138
TI  - Disturbed cholesterol homeostasis in a peroxisome-deficient PEX2 knockout mouse
      model.
AB  - We evaluated the major pathways of cholesterol regulation in the peroxisome
      deficient PEX2(-/-) mouse, a model for Zellweger syndrome. Zellweger syndrome is
      a lethal inherited disorder characterized by severe defects in peroxisome
      biogenesis and peroxisomal protein import. Compared with wild-type mice, PEX2(-/
      ) mice have decreased total and high-density lipoprotein cholesterol levels in
      plasma. Hepatic expression of the SREBP-2 gene is increased 2.5-fold in PEX2(-/-)
      mice and is associated with increased activities and increased protein and
      expression levels of SREBP-2-regulated cholesterol biosynthetic enzymes. However,
      the upregulated cholesterogenic enzymes appear to function with altered
      efficiency, associated with the loss of peroxisomal compartmentalization. The
      rate of cholesterol biosynthesis in 7- to 9-day-old PEX2(-/-) mice is markedly
      increased in most tissues, except in the brain and kidneys, where it is reduced.
      While the cholesterol content of most tissues is normal in PEX2(-/-) mice, in the
      knockout mouse liver it is decreased by 40% relative to that in control mice. The
      classic pathway of bile acid biosynthesis is downregulated in PEX2(-/-) mice.
      However, expression of CYP27A1, the rate-determining enzyme in the alternate
      pathway of bile acid synthesis, is upregulated threefold in the PEX2(-/-) mouse
      liver. The expression of hepatic ATP-binding cassette (ABC) transporters (ABCA1
      and ABCG1) involved in cholesterol efflux is not affected in PEX2(-/-) mice.
      These data illustrate the diversity in cholesterol regulatory responses among
      different organs in postnatal peroxisome-deficient mice and demonstrate that
      peroxisomes are critical for maintaining cholesterol homeostasis in the neonatal
      mouse.

PMID- 14673139
TI  - Selective estrogen receptor modulators 4-hydroxytamoxifen and raloxifene impact
      the stability and function of SRC-1 and SRC-3 coactivator proteins.
AB  - Proteasome-mediated protein degradation has been implicated in playing a role in
      nuclear receptor-mediated gene expression; inhibition of the proteasome impairs
      the transcriptional activity of estrogen receptor alpha (ERalpha) and most other
      nuclear receptors. This coincides with blockage of agonist-dependent degradation
      of the receptor and elevation of the steady-state levels of SRC family
      coactivators and CBP. Here, we examined the effects that different ERalpha
      ligands have on coactivator protein steady-state levels and demonstrate that the
      selective ER modulators (SERMs) 4-hydroxytamoxifen (4HT) and raloxifene are able
      to elevate SRC-1 and SRC-3 protein levels. Using the HeLa cell line, we show that
      this effect is ERalpha dependent. Consistent with the observed increase in
      coactivator protein levels, we were also able to observe an increase in the
      transcriptional activity of other nuclear receptors in SERM-treated cells.
      Information presented here demonstrates an unexpected consequence of SERM
      treatment, which could help further define the complex tissue responses to 4HT
      and raloxifene, and suggests that these ligands can have a broad biological
      action, stimulating the transcriptional activity of other nuclear receptors.

PMID- 14673140
TI  - Upregulation of the Catalytic Telomerase Subunit by the Transcription Factor ER81
      and Oncogenic HER2/Neu, Ras, or Raf.
AB  - One hallmark of tumor formation is the transcriptional upregulation of human
      telomerase reverse transcriptase, hTERT, and the resultant induction of
      telomerase activity. However, little is presently understood about how hTERT is
      differentially activated in tumor cells versus normal somatic cells.
      Specifically, it is unclear if oncoproteins can directly elicit hTERT expression.
      To this end, we now show that three oncoproteins, HER2/Neu, Ras, and Raf,
      stimulate hTERT promoter activity via the ETS transcription factor ER81 and ERK
      mitogen-activated protein (MAP) kinases. Mutating ER81 binding sites in the hTERT
      promoter or suppression of ERK MAP kinase-dependent phosphorylation of ER81
      rendered the hTERT promoter unresponsive to HER2/Neu. Further, expression of
      dominant-negative ER81 or inhibition of HER2/Neu significantly attenuated
      telomerase activity in HER2/Neu-overexpressing SKBR3 breast cancer cells.
      Moreover, HER2/Neu, Ras, and Raf collaborated with ER81 to enhance endogenous
      hTERT gene transcription and telomerase activity in hTERT-negative,
      nonimmortalized BJ foreskin fibroblasts. Accordingly, hTERT expression was
      increased in HER2/Neu-positive breast tumors and breast tumor cell lines relative
      to their HER2/Neu-negative counterparts. Collectively, our data elucidated a
      mechanism whereby three prominent oncoproteins, HER2/Neu, Ras, and Raf, may
      facilitate tumor formation by inducing hTERT expression in nonimmortalized cells
      via the transcription factor ER81.

PMID- 14673141
TI  - Transcription factor Nrf2 regulates inflammation by mediating the effect of 15
      deoxy-Delta(12,14)-prostaglandin j(2).
AB  - Activated macrophages express high levels of Nrf2, a transcription factor that
      positively regulates the gene expression of antioxidant and detoxication enzymes.
      In this study, we examined how Nrf2 contributes to the anti-inflammatory process.
      As a model system of acute inflammation, we administered carrageenan to induce
      pleurisy and found that in Nrf2-deficient mice, tissue invasion by neutrophils
      persisted during inflammation and the recruitment of macrophages was delayed.
      Using an antibody against 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)),
      it was observed that macrophages from pleural lavage accumulate 15d-PGJ(2). We
      show that in mouse peritoneal macrophages 15d-PGJ(2) can activate Nrf2 by forming
      adducts with Keap1, resulting in an Nrf2-dependent induction of heme oxygenase 1
      and peroxiredoxin I (PrxI) gene expression. Administration of the cyclooxygenase
      2 inhibitor NS-398 to mice with carrageenan-induced pleurisy caused persistence
      of neutrophil recruitment and, in macrophages, attenuated the 15d-PGJ(2)
      accumulation and PrxI expression. Administration of 15d-PGJ(2) into the pleural
      space of NS-398-treated wild-type mice largely counteracted both the decrease in
      PrxI and persistence of neutrophil recruitment. In contrast, these changes did
      not occur in the Nrf2-deficient mice. These results demonstrate that Nrf2
      regulates the inflammation process downstream of 15d-PGJ(2) by orchestrating the
      recruitment of inflammatory cells and regulating the gene expression within those
      cells.

PMID- 14673142
TI  - Aberrant processing of the WSC family and Mid2p cell surface sensors results in
      cell death of Saccharomyces cerevisiae O-mannosylation mutants.
AB  - Protein O mannosylation is a crucial protein modification in uni- and
      multicellular eukaryotes. In humans, a lack of O-mannosyl glycans causes
      congenital muscular dystrophies that are associated with brain abnormalities. In
      yeast, protein O mannosylation is vital; however, it is not known why impaired O
      mannosylation results in cell death. To address this question, we analyzed the
      conditionally lethal Saccharomyces cerevisiae protein O-mannosyltransferase pmt2
      pmt4Delta mutant. We found that pmt2 pmt4Delta cells lyse as small-budded cells
      in the absence of osmotic stabilization and that treatment with mating pheromone
      causes pheromone-induced cell death. These phenotypes are partially suppressed by
      overexpression of upstream elements of the protein kinase C (PKC1) cell integrity
      pathway, suggesting that the PKC1 pathway is defective in pmt2 pmt4Delta mutants.
      Congruently, induction of Mpk1p/Slt2p tyrosine phosphorylation does not occur in
      pmt2 pmt4Delta mutants during exposure to mating pheromone or elevated
      temperature. Detailed analyses of the plasma membrane sensors of the PKC1 pathway
      revealed that Wsc1p, Wsc2p, and Mid2p are aberrantly processed in pmt mutants.
      Our data suggest that in yeast, O mannosylation increases the activity of Wsc1p,
      Wsc2p, and Mid2p by enhancing their stability. Reduced O mannosylation leads to
      incorrect proteolytic processing of these proteins, which in turn results in
      impaired activation of the PKC1 pathway and finally causes cell death in the
      absence of osmotic stabilization.

PMID- 14673143
TI  - A novel notch protein, N2N, targeted by neutrophil elastase and implicated in
      hereditary neutropenia.
AB  - Mutations in ELA2, encoding the human serine protease neutrophil elastase, cause
      cyclic and severe congenital neutropenia, and recent evidence indicates that the
      mutations alter the membrane trafficking of neutrophil elastase. These disorders
      feature impaired bone marrow production of neutrophils along with excess
      monocytes-terminally differentiated lineages corresponding to the two alternative
      fates of myeloid progenitor cells. We utilized a modified yeast two-hybrid system
      and identified a new, widely expressed gene, N2N, whose product is homologous to
      Notch2, that interacts with neutrophil elastase. N2N is a 36-kDa protein
      distributed throughout the cell and secreted. Its amino-terminal sequence
      consists of several EGF repeats identical to those of the extracellular region of
      Notch2, and its carboxyl terminus contains a unique 24-residue domain required
      for interaction with neutrophil elastase. Neutrophil elastase cleaves N2N within
      EGF repeats in vitro and in living cells, but the C-terminal domain retards
      proteolysis. In vitro, N2N represses transcriptional activities of Notch
      proteins. Disease-causing mutations of neutrophil elastase disrupt the
      interaction with N2N, impair proteolysis of N2N and Notch2, and interfere with
      Notch2 signaling, suggesting defective proteolysis of an inhibitory form of Notch
      as an explanation for the alternate switching of cell fates characteristic of
      hereditary neutropenia.

PMID- 14673144
TI  - Activation of Syk protein tyrosine kinase in response to osmotic stress requires
      interaction with p21-activated protein kinase Pak2/gamma-PAK.
AB  - The p21-activated serine/threonine protein kinase Pak2/gamma-PAK and the
      nonreceptor type of protein tyrosine kinase Syk are known to be activated when
      the cells are exposed to osmotic stress. The purpose of the present study was to
      examine whether Pak2 and Syk functionally cooperate in cellular signaling.
      Cotransfection studies revealed that Pak2 associates with Syk in COS cells. The
      constitutively active form of Cdc42 increases the association of Pak2 with Syk.
      Pak2 coexpressed with an inactive form of Cdc42 or kinase-inactive Pak2 interacts
      to a lesser extent with Syk, suggesting that Pak2-Syk association is enhanced by
      Pak2 activation. Interaction with Pak2 enhances the intrinsic kinase activity of
      Syk. This is supported by in vitro studies showing that Pak2 phosphorylates and
      activates Syk. Treatment of cells with sorbitol to induce hyperosmolarity results
      in the translocation of Pak2 and Syk to the region surrounding the nucleus and in
      dramatic enhancement of their association. Furthermore, cotransfection of Pak2
      and Syk leads to the activation of c-Jun N-terminal kinase (JNK) under
      hyperosmotic conditions. Pak2 short interfering RNA suppresses sorbitol-mediated
      activation of endogenous Syk and JNK, thus identifying a novel pathway for JNK
      activation by Cdc42. These results demonstrate that Pak2 and Syk positively
      cooperate to regulate cellular responses to stress.

PMID- 14673145
TI  - Specific and covalent targeting of conjugating and deconjugating enzymes of
      ubiquitin-like proteins.
AB  - Modification of proteins by ubiquitin (Ub)-like proteins (UBLs) plays an
      important role in many cellular processes, including cell cycle progression,
      nuclear transport, and autophagy. Protein modification occurs via UBL-conjugating
      and -deconjugating enzymes, which presumably exert a regulatory function by
      determining the conjugation status of the substrate proteins. To target and
      identify UBL-modifying enzymes, we produced Nedd8, ISG15, and SUMO-1 in
      Escherichia coli and equipped them with a C-terminal electrophilic trap (vinyl
      sulfone [VS]) via an intein-based method. These C-terminally modified UBL probes
      reacted with purified UBL-activating (E1), -conjugating (E2), and -deconjugating
      enzymes in a covalent fashion. Modified UBLs were radioiodinated and incubated
      with cell lysates prepared from mouse cell lines and tissues to allow
      visualization of polypeptides reactive with individual UBL probes. The cell type-
      and tissue-specific labeling patterns observed for the UBL probes reflect
      distinct expression profiles of active enzymes, indicating tissue-specific
      functions of UBLs. We identify Ub C-terminal hydrolase L1 (UCH-L1) and
      DEN1/NEDP1/SENP8, in addition to UCH-L3, as proteases with specificity for Nedd8.
      The Ub-specific protease isopeptidase T/USP5 is shown to react with ISG15-VS.
      Furthermore, we demonstrate that the desumoylation enzyme SuPr-1 can be modified
      by SUMO-1-VS, a modification that is dependent on the SuPr-1 active-site
      cysteine. The UBL probes described here will be valuable tools for the further
      characterization of the enzymatic pathways that govern modification by UBLs.

PMID- 14673146
TI  - Essential role for ADAM19 in cardiovascular morphogenesis.
AB  - Congenital heart disease is the most common form of human birth defects, yet much
      remains to be learned about its underlying causes. Here we report that mice
      lacking functional ADAM19 (mnemonic for a disintegrin and metalloprotease 19)
      exhibit severe defects in cardiac morphogenesis, including a ventricular septal
      defect (VSD), abnormal formation of the aortic and pulmonic valves, leading to
      valvular stenosis, and abnormalities of the cardiac vasculature. During mouse
      development, ADAM19 is highly expressed in the conotruncus and the endocardial
      cushion, structures that give rise to the affected heart valves and the
      membranous ventricular septum. ADAM19 is also highly expressed in osteoblast-like
      cells in the bone, yet it does not appear to be essential for bone growth and
      skeletal development. Most adam19(-/-) animals die perinatally, likely as a
      result of their cardiac defects. These findings raise the possibility that
      mutations in ADAM19 may contribute to human congenital heart valve and septal
      defects.

PMID- 14673147
TI  - Targeted nuclear import of open reading frame 1 protein is required for in vivo
      retrotransposition of a telomere-specific non-long terminal repeat
      retrotransposon, SART1.
AB  - Non-long terminal repeat (non-LTR) retrotransposons, most of which carry two open
      reading frames (ORFs), are abundant mobile elements that are distributed widely
      among eukaryotes. ORF2 encodes enzymatic domains, such as reverse transcriptase,
      that are conserved in all retroelements, but the functional roles of ORF1 in vivo
      are little understood. We show with green fluorescent protein-ORF1 fusion
      proteins that the ORF1 proteins of SART1, a telomeric repeat-specific non-LTR
      retrotransposon in Bombyx mori, are transported into the nucleus to produce a
      dotted localization pattern. Nuclear localization signals N1 (RRKR) and N2
      (PSKRGRG) at the N terminus and a highly basic region in the center of SART1 ORF1
      are involved in nuclear import and the dotted localization pattern in the
      nucleus, respectively. An in vivo retrotransposition assay clarified that at
      least three ORF1 domains, N1/N2, the central basic domain, and CCHC zinc fingers
      are required for SART1 retrotransposition. The nuclear import activity of SART1
      ORF1 makes it clear that the ORF1 proteins of non-LTR retrotransposons work
      mainly in the nucleus, in contrast to the cytoplasmic action of Gag proteins of
      LTR elements. The functional domains found here in SART1 ORF1 will be useful for
      developing a more efficient and target-specific LINE-based gene delivery vector.

PMID- 14673148
TI  - Repair kinetics of genomic interstrand DNA cross-links: evidence for DNA double
      strand break-dependent activation of the Fanconi anemia/BRCA pathway.
AB  - The detailed mechanisms of DNA interstrand cross-link (ICL) repair and the
      involvement of the Fanconi anemia (FA)/BRCA pathway in this process are not
      known. Present models suggest that recognition and repair of ICL in human cells
      occur primarily during the S phase. Here we provide evidence for a refined model
      in which ICLs are recognized and are rapidly incised by ERCC1/XPF independent of
      DNA replication. However, the incised ICLs are then processed further and DNA
      double-strand breaks (DSB) form exclusively in the S phase. FA cells are fully
      proficient in the sensing and incision of ICL as well as in the subsequent
      formation of DSB, suggesting a role of the FA/BRCA pathway downstream in ICL
      repair. In fact, activation of FANCD2 occurs slowly after ICL treatment and
      correlates with the appearance of DSB in the S phase. In contrast, activation is
      rapid after ionizing radiation, indicating that the FA/BRCA pathway is
      specifically activated upon DSB formation. Furthermore, the formation of FANCD2
      foci is restricted to a subpopulation of cells, which can be labeled by
      bromodeoxyuridine incorporation. We therefore conclude that the FA/BRCA pathway,
      while being dispensable for the early events in ICL repair, is activated in S
      phase cells after DSB have formed.

PMID- 14673149
TI  - Spt10-dependent transcriptional activation in Saccharomyces cerevisiae requires
      both the Spt10 acetyltransferase domain and Spt21.
AB  - Histone levels are a key factor in several nuclear processes, including
      transcription and chromosome segregation. Previous studies have demonstrated that
      Spt10 and Spt21 are required for the normal transcription of a subset of the
      histone genes in Saccharomyces cerevisiae, and sequence analysis has suggested
      that Spt10 is an acetyltransferase. We have now characterized several aspects of
      transcriptional activation of histone genes by Spt10 in vivo. Our results show
      that activation by Spt10 is dependent on its acetyltransferase domain. At HTA2
      HTB2, the histone locus whose transcription is most strongly dependent on Spt10,
      Spt10 is physically recruited to the promoter in an Spt21-dependent and a cell
      cycle-dependent manner. Furthermore, Spt10 and Spt21 directly interact. These
      results, taken together with the identification of spt10 mutations that suppress
      an spt21Delta mutation, suggest a model for transcriptional activation by Spt10
      and Spt21.

PMID- 14673150
TI  - A network of immediate early gene products propagates subtle differences in
      mitogen-activated protein kinase signal amplitude and duration.
AB  - The strength and duration of mitogen-activated protein kinase (MAPK) signaling
      have been shown to regulate cell fate in different cell types. In this study, a
      general mechanism is described that explains how subtle differences in signaling
      kinetics are translated into a specific biological outcome. In fibroblasts, the
      expression of immediate early gene (IEG)-encoded Fos, Jun, Myc, and early growth
      response gene 1 (Egr-1) transcription factors is significantly extended by
      sustained extracellular signal-regulated kinase 1 and 2 (ERK1 and -2) signaling.
      Several of these proteins contain functional docking site for ERK, FXFP (DEF)
      domains that serve to locally concentrate the active kinase, thus showing that
      they can function as ERK sensors. Sustained ERK signaling regulates the
      posttranslational modifications of these IEG-encoded sensors, which contributes
      to their sustained expression during the G(1)-S transition. DEF domain-containing
      sensors can also interpret the small changes in ERK signal strength that arise
      from less than a threefold reduction in agonist concentration. As a result,
      downstream target gene expression and cell cycle progression are significantly
      changed.

PMID- 14673151
TI  - Assessment of splice variant-specific functions of desmocollin 1 in the skin.
AB  - Desmocollin 1 (Dsc1) is part of a desmosomal cell adhesion receptor formed in
      terminally differentiating keratinocytes of stratified epithelia. The dsc1 gene
      encodes two proteins (Dsc1a and Dsc1b) that differ only with respect to their
      COOH-terminal cytoplasmic amino acid sequences. On the basis of in vitro
      experiments, it is thought that the Dsc1a variant is essential for assembly of
      the desmosomal plaque, a structure that connects desmosomes to the intermediate
      filament cytoskeleton of epithelial cells. We have generated mice that synthesize
      a truncated Dsc1 receptor that lacks both the Dsc1a- and Dsc1b-specific COOH
      terminal domains. This mutant transmembrane receptor, which does not bind the
      common desmosomal plaque proteins plakoglobin and plakophilin 1, is integrated
      into functional desmosomes. Interestingly, our mutant mice did not show the
      epidermal fragility previously observed in dsc1-null mice. This suggests that
      neither the Dsc1a- nor the Dsc1b-specific COOH-terminal cytoplasmic domain is
      required for establishing and maintaining desmosomal adhesion. However, a
      comparison of our mutants with dsc1-null mice suggests that the Dsc1
      extracellular domain is necessary to maintain structural integrity of the skin.

PMID- 14673152
TI  - CD3/CD28 costimulation-induced NF-kappaB activation is mediated by recruitment of
      protein kinase C-theta, Bcl10, and IkappaB kinase beta to the immunological
      synapse through CARMA1.
AB  - CARMA1 (also known as CARD11) is a scaffold molecule and contains a caspase
      recruitment domain (CARD) and a membrane-associated guanylate kinase-like (MAGUK)
      domain. It plays an essential role in mediating CD3/CD28 costimulation-induced NF
      kappaB activation. However, the molecular mechanism by which CARMA1 mediates
      costimulatory signals remains to be determined. Here, we show that CARMA1 is
      constitutively associated with the cytoplasmic membrane. This membrane
      association is essential for the function of CARMA1, since a mutant of CARMA1,
      CARMA1(L808P), that is defective in the membrane association cannot rescue
      CD3/CD28 costimulation-induced NF-kappaB activation in JPM50.6 CARMA1-deficient T
      cells. Although CD3/CD28 costimulation effectively induces the formation of the
      immunological synapse in CARMA1-deficient T cells, the recruitment of protein
      kinase C-theta (PKC-theta), Bcl10, and IkappaB kinase beta (IKKbeta) into lipid
      rafts of the immunological synapse is defective. Moreover, expression of wild
      type CARMA1, but not CARMA1(L808P), restores the recruitment of PKC-theta, Bcl10,
      and IKKbeta into lipid rafts in CARMA1-deficient T cells. Consistently,
      expression of a mutant CARMA1, CARMA1(DeltaCD), that cannot associate with Bcl10
      failed to restore CD3/CD28 costimulation-induced NF-kappaB activation in JPM50.6
      cells, whereas expression of Bcl10-CARMA(DeltaCD) fusion protein effectively
      restored this NF-kappaB activation. Together, these results indicate that CARMA1
      mediates CD3/CD28 costimulation-induced NF-kappaB activation by recruiting
      downstream signaling components into the immunological synapse.

PMID- 14673153
TI  - The homeobox gene Caudal regulates constitutive local expression of antimicrobial
      peptide genes in Drosophila epithelia.
AB  - In Drosophila melanogaster, although the NF-kappaB transcription factors play a
      pivotal role in the inducible expression of innate immune genes, such as
      antimicrobial peptide genes, the exact regulatory mechanism of the tissue
      specific constitutive expression of these genes in barrier epithelia is largely
      unknown. Here, we show that the Drosophila homeobox gene product Caudal functions
      as the innate immune transcription modulator that is responsible for the
      constitutive local expression of antimicrobial peptides cecropin and drosomycin
      in a tissue-specific manner. These results suggest that certain epithelial
      tissues have evolved a unique constitutive innate immune strategy by recruiting a
      developmental "master control" gene.

PMID- 14673154
TI  - Mdm2 regulates p53 independently of p19(ARF) in homeostatic tissues.
AB  - Tumor suppressor proteins must be exquisitely regulated since they can induce
      cell death while preventing cancer. For example, the p19(ARF) tumor suppressor
      (p14(ARF) in humans) appears to stimulate the apoptotic function of the p53 tumor
      suppressor to prevent lymphomagenesis and carcinogenesis induced by oncogene
      overexpression. Here we present a genetic approach to defining the role of
      p19(ARF) in regulating the apoptotic function of p53 in highly proliferating,
      homeostatic tissues. In contrast to our expectation, p19(ARF) did not activate
      the apoptotic function of p53 in lymphocytes or epithelial cells. These results
      demonstrate that the mechanisms that control p53 function during homeostasis
      differ from those that are critical for tumor suppression. Moreover, the
      Mdm2/p53/p19(ARF) pathway appears to exist only under very restricted conditions.

PMID- 14673155
TI  - Elucidation of the c-Jun N-terminal kinase pathway mediated by Estein-Barr virus
      encoded latent membrane protein 1.
AB  - Epstein-Barr virus (EBV) is associated with several human diseases including
      infectious mononucleosis and nasopharyngeal carcinoma. EBV-encoded latent
      membrane protein 1 (LMP1) is oncogenic and indispensable for cellular
      transformation caused by EBV. Expression of LMP1 in host cells constitutively
      activates both the c-Jun N-terminal kinase (JNK) and NF-kappaB pathways, which
      contributes to the oncogenic effect of LMP1. However, the underlying signaling
      mechanisms are not very well understood. Based mainly on overexpression studies
      with various dominant-negative constructs, LMP1 was generally thought to
      functionally mimic members of the tumor necrosis factor (TNF) receptor
      superfamily in signaling. In contrast to the prevailing paradigm, using embryonic
      fibroblasts from different knockout mice and the small interfering RNA technique,
      we find that the LMP1-mediated JNK pathway is distinct from those mediated by
      either TNF-alpha or interleukin-1. Moreover, we have further elucidated the LMP1
      mediated JNK pathway by demonstrating that LMP1 selectively utilizes TNF receptor
      associated factor 6, TAK1/TAB1, and c-Jun N-terminal kinase kinases 1 and 2 to
      activate JNK.

PMID- 14673156
TI  - mTOR controls cell cycle progression through its cell growth effectors S6K1 and
      4E-BP1/eukaryotic translation initiation factor 4E.
AB  - The mammalian target of rapamycin (mTOR) integrates nutrient and mitogen signals
      to regulate cell growth (increased cell mass and cell size) and cell division.
      The immunosuppressive drug rapamycin inhibits cell cycle progression via
      inhibition of mTOR; however, the signaling pathways by which mTOR regulates cell
      cycle progression have remained poorly defined. Here we demonstrate that
      restoration of mTOR signaling (by using a rapamycin-resistant mutant of mTOR)
      rescues rapamycin-inhibited G(1)-phase progression, and restoration of signaling
      along the mTOR-dependent S6K1 or 4E-BP1/eukaryotic translation initiation factor
      4E (eIF4E) pathways provides partial rescue. Furthermore, interfering RNA
      mediated reduction of S6K1 expression or overexpression of mTOR-insensitive 4E
      BP1 isoforms that block eIF4E activity inhibit G(1)-phase progression
      individually and additively. Thus, the activities of both the S6K1 and 4E
      BP1/eIF4E pathways are required for and independently mediate mTOR-dependent G(1)
      phase progression. In addition, overexpression of constitutively active mutants
      of S6K1 or wild-type eIF4E accelerates serum-stimulated G(1)-phase progression,
      and stable expression of wild-type S6K1 confers a proliferative advantage in low
      serum-containing media, suggesting that the activity of each of these pathways is
      limiting for cell proliferation. These data demonstrate that, as for the
      regulation of cell growth and cell size, the S6K1 and 4E-BP1/eIF4E pathways each
      represent critical mediators of mTOR-dependent cell cycle control.

PMID- 14673157
TI  - Noncompetitive counteractions of DNA polymerase epsilon and ISW2/yCHRAC for
      epigenetic inheritance of telomere position effect in Saccharomyces cerevisiae.
AB  - Relocation of euchromatic genes near the heterochromatin region often results in
      mosaic gene silencing. In Saccharomyces cerevisiae, cells with the genes inserted
      at telomeric heterochromatin-like regions show a phenotypic variegation known as
      the telomere-position effect, and the epigenetic states are stably passed on to
      following generations. Here we show that the epigenetic states of the telomere
      gene are not stably inherited in cells either bearing a mutation in a catalytic
      subunit (Pol2) of replicative DNA polymerase epsilon (Pol epsilon) or lacking one
      of the nonessential and histone fold motif-containing subunits of Pol epsilon,
      Dpb3 and Dpb4. We also report a novel and putative chromatin-remodeling complex,
      ISW2/yCHRAC, that contains Isw2, Itc1, Dpb3-like subunit (Dls1), and Dpb4. Using
      the single-cell method developed in this study, we demonstrate that without Pol
      epsilon and ISW2/yCHRAC, the epigenetic states of the telomere are frequently
      switched. Furthermore, we reveal that Pol epsilon and ISW2/yCHRAC function
      independently: Pol epsilon operates for the stable inheritance of a silent state,
      while ISW2/yCHRAC works for that of an expressed state. We therefore propose that
      inheritance of specific epigenetic states of a telomere requires at least two
      counteracting regulators.

PMID- 14673158
TI  - Cited1 is required in trophoblasts for placental development and for embryo
      growth and survival.
AB  - Cited1 is a transcriptional cofactor that interacts with Smad4, estrogen
      receptors alpha and beta, TFAP2, and CBP/p300. It is expressed in a restricted
      manner in the embryo as well as in extraembryonic tissues during embryonic
      development. In this study we report the engineering of a loss-of-function Cited1
      mutation in the mouse. Cited1 null mutants show growth restriction at 18.5 days
      postcoitum, and most of them die shortly after birth. Half the heterozygous
      females, i.e., those that carry a paternally inherited wild-type Cited1 allele,
      are similarly affected. Cited1 is normally expressed in trophectoderm-derived
      cells of the placenta; however, in these heterozygous females, Cited1 is not
      expressed in these cells. This occurs because Cited1 is located on the X
      chromosome, and thus the wild-type Cited1 allele is not expressed because the
      paternal X chromosome is preferentially inactivated. Loss of Cited1 resulted in
      abnormal placental development. In mutants, the spongiotrophoblast layer is
      irregular in shape and enlarged while the labyrinthine layer is reduced in size.
      In addition, the blood spaces within the labyrinthine layer are disrupted; the
      maternal sinusoids are considerably larger in mutants, leading to a reduction in
      the surface area available for nutrient exchange. We conclude that Cited1 is
      required in trophoblasts for normal placental development and subsequently for
      embryo viability.

PMID- 14673159
TI  - Transcription Factors Pax6 and AP-2alpha Interact To Coordinate Corneal
      Epithelial Repair by Controlling Expression of Matrix Metalloproteinase
      Gelatinase B.
AB  - Pax6 is a paired box containing transcription factor that resides at the top of a
      genetic hierarchy controlling eye development. It continues to be expressed in
      tissues of the adult eye, but its role in this capacity is unclear. Pax6 is
      present in the adult corneal epithelium, and we showed that the amount of Pax6 is
      increased at the migrating front as the epithelium resurfaces the cornea after
      injury. We also showed that Pax6 controls activity of the transcriptional
      promoter for the matrix metalloproteinase, gelatinase B (gelB; MMP-9) in cell
      culture transfection studies. gelB expression is turned on at the migrating
      epithelial front in the cornea, and it coordinates and effects aspects of
      epithelial regeneration. We define here two positively acting Pax6 response
      elements in the gelB promoter. Pax6 binds directly to one of these sites through
      the paired DNA-binding domain. It binds the second site indirectly by interaction
      with AP-2alpha, a transcription factor that also exerts control over eye
      development. Pax6 control of gelB expression was examined in vivo by using a
      corneal reepithelialization model in mice heterozygous for a Pax6 paired-domain
      mutation (Sey(+/-)). A reduced Pax6 dosage in these mice resulted in a loss of
      gelB expression at the migrating epithelial front. This effect was correlated
      with an increase in inflammation and the rate of reepithelialization, a finding
      consistent with the phenotype of gelB knockout mice. Together, these data
      indicate that Pax6 controls activity of the gelB promoter through cooperative
      interactions with AP-2alpha and support an active role for Pax6 in maintenance
      and repair of the adult corneal epithelium.

PMID- 14673160
TI  - Essential role of STAT3 in body weight and glucose homeostasis.
AB  - STAT3 is a ubiquitous transcription factor that is indispensable during early
      embryogenesis. To study the functions of STAT3 postnatally, we generated
      conditional STAT3-deficient mice. To that end, STAT3(lox/lox) mice were crossed
      with mice expressing Cre under the control of rat insulin II gene promoter (RIP
      Cre mice). Immunohistochemical and Western blot analyses showed that STAT3 is
      deleted from beta cells in the islets of Langerhans. Genomic DNA PCR revealed
      that STAT3 deletion also occurred in the hypothalamus. Hypothalamic Cre
      expression was further confirmed by crossing RIP-Cre/STAT3(lox/lox) mice with the
      ROSA26 Cre reporter strain and staining for lacZ activity. Double
      immunohistochemical staining confirmed that deletion of STAT3 occurred in leptin
      receptor (OB-Rb isoform)-positive neurons. RIP-Cre/STAT3(lox/lox) mice are mildly
      hyperglycemic and hyperinsulinemic at the time of weaning, become hyperphagic
      immediately after weaning, and exhibit impaired glucose tolerance. Body weight,
      body fat, and mRNA and protein levels of leptin are all significantly increased
      in RIP-Cre/STAT3(lox/lox) mice. Administration of recombinant leptin by
      intracerebroventricular infusion failed to cause complete loss of body fat in RIP
      Cre/STAT3(lox/lox) mice. Transplantation of wild-type islets into RIP
      Cre/STAT3(lox/lox) mice also failed to decrease adiposity or to correct other
      abnormalities in these mice. These data thus suggest that loss of STAT3 in the
      hypothalamus caused by RIP-Cre action likely interferes with normal body weight
      homeostasis and glucose metabolism.

PMID- 14673161
TI  - The mouse Murr1 gene is imprinted in the adult brain, presumably due to
      transcriptional interference by the antisense-oriented U2af1-rs1 gene.
AB  - The mouse Murr1 gene contains an imprinted gene, U2af1-rs1, in its first intron.
      U2af1-rs1 shows paternal allele-specific expression and is transcribed in the
      direction opposite to that of the Murr1 gene. In contrast to a previous report of
      biallelic expression of Murr1 in neonatal mice, we have found that the maternal
      allele is expressed predominantly in the adult brain and also preferentially in
      other adult tissues. This maternal-predominant expression is not observed in
      embryonic and neonatal brains. In situ hybridization experiments that used the
      adult brain indicated that Murr1 gene was maternally expressed in neuronal cells
      in all regions of the brain. We analyzed the developmental change in the
      expression levels of both Murr1 and U2af1-rs1 in the brain and liver, and we
      propose that the maternal-predominant expression of Murr1 results from
      transcriptional interference of the gene by U2af1-rs1 through the Murr1 promoter
      region.

PMID- 14673162
TI  - ASK1 inhibits astroglial development via p38 mitogen-activated protein kinase and
      promotes neuronal differentiation in adult hippocampus-derived progenitor cells.
AB  - The mechanisms controlling differentiation and lineage specification of neural
      stem cells are still poorly understood, and many of the molecules involved in
      this process and their specific functions are yet unknown. We investigated the
      effect of apoptosis signal-regulating kinase 1 (ASK1) on neural stem cells by
      infecting adult hippocampus-derived rat progenitors with an adenovirus encoding
      the constitutively active form of ASK1. Following ASK1 overexpression, a
      significantly larger number of cells differentiated into neurons and a
      substantial increase in Mash1 transcription was observed. Moreover, a marked
      depletion of glial cells was observed, persisting even after additional treatment
      of ASK1-infected cultures with potent glia inducers such as leukemia inhibitory
      factor and bone morphogenetic protein. Analysis of the promoter for glial
      fibrillary acidic protein revealed that ASK1 acts as a potent inhibitor of glial
      specific gene transcription. However, the signal transducers and activators of
      transcription 3 (STAT3)-binding site in the promoter was dispensable, while the
      activation of p38 mitogen-activated protein kinase was crucial for this effect,
      suggesting the presence of a novel mechanism for the inhibition of glial
      differentiation.

PMID- 14673163
TI  - Mice deficient for the ets transcription factor elk-1 show normal immune
      responses and mildly impaired neuronal gene activation.
AB  - The transcription factor Elk-1 belongs to the ternary complex factor (TCF)
      subfamily of Ets proteins. TCFs interact with serum response factor to bind
      jointly to serum response elements in the promoters of immediate-early genes
      (IEGs). TCFs mediate the rapid transcriptional response of IEGs to various
      extracellular stimuli which activate mitogen-activated protein kinase signaling.
      To investigate physiological functions of Elk-1 in vivo, we generated Elk-1
      deficient mice by homologous recombination in embryonic stem cells. These animals
      were found to be phenotypically indistinguishable from their wild-type
      littermates. Histological analysis of various tissues failed to reveal any
      differences between Elk-1 mutant and wild-type mice. Elk-1 deficiency caused no
      changes in the proteomic displays of brain or spleen extracts. Also, no
      immunological defects could be detected in mice lacking Elk-1, even upon
      infection with coxsackievirus B3. In mouse embryonic fibroblasts, Elk-1 was
      dispensable for c-fos and Egr-1 transcriptional activation upon stimulation with
      serum, lysophosphatidic acid, or tetradecanoyl phorbol acetate. However, in
      brains of Elk-1-deficient mice, cortical and hippocampal CA1 expression of c-fos,
      but not Egr-1 or c-Jun, was markedly reduced 4 h following kainate-induced
      seizures. This was not accompanied by altered patterns of neuronal apoptosis.
      Collectively, our data indicate that Elk-1 is essential neither for mouse
      development nor for adult life, suggesting compensatory activities by other TCFs.

PMID- 14673164
TI  - Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone
      deacetylase 1 (HDAC1)/HDAC2 complex.
AB  - The transcription factor Snail has been described as a direct repressor of E
      cadherin expression during development and carcinogenesis; however, the specific
      mechanisms involved in this process remain largely unknown. Here we show that
      mammalian Snail requires histone deacetylase (HDAC) activity to repress E
      cadherin promoter and that treatment with trichostatin A (TSA) is sufficient to
      block the repressor effect of Snail. Moreover, overexpression of Snail is
      correlated with deacetylation of histones H3 and H4 at the E-cadherin promoter,
      and TSA treatment in Snail-expressing cells reverses the acetylation status of
      histones. Additionally, we demonstrate that Snail interacts in vivo with the E
      cadherin promoter and recruits HDAC activity. Most importantly, we demonstrate an
      interaction between Snail, histone deacetylase 1 (HDAC1) and HDAC2, and the
      corepressor mSin3A. This interaction is dependent on the SNAG domain of Snail,
      indicating that the Snail transcription factor mediates the repression by
      recruitment of chromatin-modifying activities, forming a multimolecular complex
      to repress E-cadherin expression. Our results establish a direct causal
      relationship between Snail-dependent repression of E-cadherin and the
      modification of chromatin at its promoter.

PMID- 14673165
TI  - p50alpha/p55alpha phosphoinositide 3-kinase knockout mice exhibit enhanced
      insulin sensitivity.
AB  - Class Ia phosphoinositide (PI) 3-kinases are heterodimers composed of a
      regulatory and a catalytic subunit and are essential for the metabolic actions of
      insulin. In addition to p85alpha and p85beta, insulin-sensitive tissues such as
      fat, muscle, and liver express the splice variants of the pik3r1 gene, p50alpha
      and p55alpha. To define the role of these variants, we have created mice with a
      deletion of p50alpha and p55alpha by using homologous recombination. These mice
      are viable, grow normally, and maintain normal blood glucose levels but have
      lower fasting insulin levels. Results of an insulin tolerance test indicate that
      p50alpha/p55alpha knockout mice have enhanced insulin sensitivity in vivo, and
      there is an increase in insulin-stimulated glucose transport in isolated extensor
      digitorum longus muscle tissues and adipocytes. In muscle, loss of
      p50alpha/p55alpha results in reduced levels of insulin-stimulated insulin
      receptor substrate 1 (IRS-1) and phosphotyrosine-associated PI 3-kinase but
      enhanced levels of IRS-2-associated PI 3-kinase and Akt activation, whereas in
      adipocytes levels of both insulin-stimulated PI 3-kinase and Akt are unchanged.
      Despite this, adipocytes of the knockout mice are smaller and have increased
      glucose uptake with altered glucose metabolic pathways. When treated with gold
      thioglucose, p50alpha/p55alpha knockout mice become hyperphagic like their wild
      type littermates. However, they accumulate less fat and become mildly less
      hyperglycemic and markedly less hyperinsulinemic. Taken together, these data
      indicate that p50alpha and p55alpha play an important role in insulin signaling
      and action, especially in lipid and glucose metabolism.

PMID- 14673166
TI  - S-nitrosylation of IRP2 regulates its stability via the ubiquitin-proteasome
      pathway.
AB  - Nitric oxide (NO) is an important signaling molecule that interacts with
      different targets depending on its redox state. NO can interact with thiol groups
      resulting in S-nitrosylation of proteins, but the functional implications of this
      modification are not yet fully understood. We have reported that treatment of RAW
      264.7 cells with NO caused a decrease in levels of iron regulatory protein 2
      (IRP2), which binds to iron-responsive elements present in untranslated regions
      of mRNAs for several proteins involved in iron metabolism. In this study, we show
      that NO causes S-nitrosylation of IRP2, both in vitro and in vivo, and this
      modification leads to IRP2 ubiquitination followed by its degradation in the
      proteasome. Moreover, mutation of one cysteine (C178S) prevents NO-mediated
      degradation of IRP2. Hence, S-nitrosylation is a novel signal for IRP2
      degradation via the ubiquitin-proteasome pathway.

PMID- 14673167
TI  - Activation of the RAS/cyclic AMP pathway suppresses a TOR deficiency in yeast.
AB  - The TOR (target of rapamycin) and RAS/cyclic AMP (cAMP) signaling pathways are
      the two major pathways controlling cell growth in response to nutrients in yeast.
      In this study we examine the functional interaction between TOR and the RAS/cAMP
      pathway. First, activation of the RAS/cAMP signaling pathway confers pronounced
      resistance to rapamycin. Second, constitutive activation of the RAS/cAMP pathway
      prevents several rapamycin-induced responses, such as the nuclear translocation
      of the transcription factor MSN2 and induction of stress genes, the accumulation
      of glycogen, the induction of autophagy, the down-regulation of ribosome
      biogenesis (ribosomal protein gene transcription and RNA polymerase I and III
      activity), and the down-regulation of the glucose transporter HXT1. Third, many
      of these TOR-mediated responses are independent of the previously described TOR
      effectors TAP42 and the type 2A-related protein phosphatase SIT4. Conversely, TOR
      controlled TAP42/SIT4-dependent events are not affected by the RAS/cAMP pathway.
      Finally, and importantly, TOR controls the subcellular localization of both the
      protein kinase A catalytic subunit TPK1 and the RAS/cAMP signaling-related kinase
      YAK1. Our findings suggest that TOR signals through the RAS/cAMP pathway,
      independently of TAP42/SIT4. Therefore, the RAS/cAMP pathway may be a novel TOR
      effector branch.

PMID- 14673168
TI  - Mutations in the gal83 glycogen-binding domain activate the snf1/gal83 kinase
      pathway by a glycogen-independent mechanism.
AB  - The yeast Snf1 kinase and its mammalian ortholog, AMP-activated protein kinase
      (AMPK), regulate responses to metabolic stress. Previous studies identified a
      glycogen-binding domain in the AMPK beta1 subunit, and the sequence is conserved
      in the Snf1 kinase beta subunits Gal83 and Sip2. Here we use genetic analysis to
      assess the role of this domain in vivo. Alteration of Gal83 at residues that are
      important for glycogen binding of AMPK beta1 abolished glycogen binding in vitro
      and caused diverse phenotypes in vivo. Various Snf1/Gal83-dependent processes
      were upregulated, including glycogen accumulation, expression of RNAs encoding
      glycogen synthase, haploid invasive growth, the transcriptional activator
      function of Sip4, and activation of the carbon source-responsive promoter
      element. Moreover, the glycogen-binding domain mutations conferred
      transcriptional regulatory phenotypes even in the absence of glycogen, as
      determined by analysis of a mutant strain lacking glycogen synthase. Thus,
      mutation of the glycogen-binding domain of Gal83 positively affects Snf1/Gal83
      kinase function by a mechanism that is independent of glycogen binding.

PMID- 14673169
TI  - Role for BRG1 in cell cycle control and tumor suppression.
AB  - Human BRG1, a subunit of the Swi/Snf chromatin remodeling apparatus, has been
      implicated in regulation of cellular proliferation and is a candidate tumor
      suppressor. Reintroduction of BRG1 into a breast tumor cell line, ALAB, carrying
      a defined mutation in the BRG1 gene, induced growth arrest. Gene expression data
      revealed that the arrest may in part be accounted for by down-regulation of
      select E2F target genes such as cyclin E, but more dramatically, by up-regulation
      of mRNAs for the cyclin-dependent kinase inhibitors p21 and p15. Protein levels
      of both p15 and p21 were induced, and p21 protein was recruited to a complex with
      cyclin-dependent kinase, CDK2, to inhibit its activity. BRG1 can associate with
      the p21 promoter in a p53-independent manner, suggesting that the induction of
      p21 by BRG1 may be direct. Further, using microarray and real-time PCR analysis
      we identified several novel BRG1-regulated genes. Our work provides further
      evidence for a role for BRG1 in the regulation of several genes involved in key
      steps in tumorigenesis and has revealed a potential mechanism for BRG1-induced
      growth arrest.

PMID- 14673170
TI  - Gata4 regulates testis expression of Dmrt1.
AB  - The doublesex and mab-3 related transcription factor 1 (Dmrt1) is a putative
      transcriptional regulator that is expressed exclusively in the gonads and is
      required for postnatal testis differentiation. Here we describe the
      transcriptional mechanisms regulating testis-specific expression of the Dmrt1
      gene. Transient-transfection analysis identified a region of the promoter between
      kb -3.2 and -2.8 that is important for Sertoli cell-specific expression. DNase I
      footprinting revealed four sites of DNA-protein interaction within this region,
      three of which were prominent in primary Sertoli cells. Analysis of these sites,
      using electrophoretic mobility shift assays, revealed that Gata4 and another
      unknown factor bound within these regions. Further transient-transfection assays
      of various mutant promoters established the functional relevance of the Gata4
      response and unknown factor-response elements, while studies of Dmrt1 expression
      in 13.5 days postcoitum Fog2 null gonads supported the in vivo importance of
      Gata4's regulation. As a whole, these studies identify Gata4 as an important
      regulator in the Dmrt1 transcriptional machinery that is responsible for robust
      expression of Dmrt1 in the testis.

PMID- 14673171
TI  - Recruitment of SWI/SNF to the human immunodeficiency virus type 1 promoter.
AB  - Following human immunodeficiency virus type 1 (HIV-1) integration into the host
      cell's genome, the 5' long terminal repeat (LTR) is packaged into a highly
      specific chromatin structure comprised of an array of nucleosomes positioned with
      respect to important DNA sequence elements that regulate the transcriptional
      activity of the provirus. While several host cell factors have been shown to be
      important for chromatin remodeling and/or basal transcription, no specific
      mechanism that relieves the transcriptional repression imposed by nuc-1, a
      positioned nucleosome that impedes the start site of transcription, has been
      found. Since phorbol esters cause the rapid disruption of nuc-1 and markedly
      stimulate HIV-1 transcription, we looked for protein factors that associate with
      this region of the HIV-1 promoter in a phorbol-ester-dependent manner. We report
      here that ATF-3, JunB, and BRG-1 (the ATPase subunit of the 2-MDa human chromatin
      remodeling machine SWI/SNF) are recruited to the 3' boundary of nuc-1 following
      phorbol myristate acetate stimulation in Jurkat T cells. Analysis of the
      recruitment of BRG-1 in nuclear extracts prepared from Jurkat T cells and
      reconstitution of an in vitro system with purified components demonstrate that
      ATF-3 is responsible for targeting human SWI/SNF (hSWI/SNF) to the HIV-1
      promoter. Importantly, this recruitment of hSWI/SNF required HMGA1 proteins.
      Further support for this conclusion comes from immunoprecipitation experiments
      showing that BRG-1 and ATF-3 can exist together in the same complex. Although ATF
      3 clearly plays a role in the specific targeting of BRG-1 to the HIV-1 promoter,
      the maintenance of a stable association between BRG-1 and chromatin appears to be
      dependent upon histone acetylation. By adding BRG-1 back into a BRG-1-deficient
      cell line (C33A cells), we demonstrate that trichostatin A strongly induces the
      5'-LTR-driven reporter transcription in a manner that is dependent upon BRG-1
      recruitment.

PMID- 14673172
TI  - Transcription termination factor reb1p causes two replication fork barriers at
      its cognate sites in fission yeast ribosomal DNA in vivo.
AB  - Polar replication fork barriers (RFBs) near the 3' end of the rRNA
      transcriptional unit are a conserved feature of ribosomal DNA (rDNA) replication
      in eukaryotes. In the mouse, in vivo studies indicate that the cis-acting Sal
      boxes required for rRNA transcription termination are also involved in
      replication fork blockage. On the contrary, in the budding yeast Saccharomyces
      cerevisiae, the rRNA transcription termination factors are not required for RFBs.
      Here we characterized the rDNA RFBs in the fission yeast Schizosaccharomyces
      pombe. S. pombe rDNA contains three closely spaced polar replication barriers
      named RFB1, RFB2, and RFB3 in the 3' to 5' order. The transcription termination
      protein reb1 and its two binding sites, present at the 3' end of the coding
      region, were required for fork arrest at RFB2 and RFB3 in vivo. On the other
      hand, fork arrest at the strongest RFB1 barrier was independent of the above
      transcription termination factors. Therefore, RFB2 and RFB3 resemble the barriers
      present in the mouse rDNA, whereas RFB1 is similar to the budding yeast RFBs.
      These results suggest that during evolution, cis- and trans-acting factors
      required for rRNA transcription termination became involved in replication fork
      blockage also. S. pombe is suggested to be a transitional species in which both
      mechanisms coexist.

PMID- 14673173
TI  - Essential role of STAT3 in postnatal survival and growth revealed by mice lacking
      STAT3 serine 727 phosphorylation.
AB  - A large number of extracellular polypeptides bound to their cognate receptors
      activate the transcription factor STAT3 by phosphorylation of tyrosine 705.
      Supplemental activation occurs when serine 727 is also phosphorylated. STAT3
      deletion in mice leads to embryonic lethality. We have produced mice with alanine
      substituted for serine 727 in STAT3 (the SA allele) to examine the function of
      serine 727 phosphorylation in vivo. Embryonic fibroblasts from SA/SA mice had
      approximately 50% of the transcriptional response of wild-type cells. However,
      SA/SA mice were viable and grossly normal. STAT3 wild-type/null (+/-) animals
      were also normal and were interbred with SA/SA mice to study SA/- mice. The SA/-
      mice progressed through gestation, showing 10 to 15% reduced birth weight, three
      fourths died soon after birth, and the SA/- survivors reached only 50 to 60% of
      normal size at 1 week of age. The lethality and decreased growth were accompanied
      by altered insulin-like growth factor 1 (IGF-1) levels in serum, establishing a
      role for the STAT3 serine phosphorylation acting through IGF-1 in embryonic and
      perinatal growth. The SA/- survivors have decreased thymocyte number associated
      with increased apoptosis, but unexpectedly normal STAT3-dependent liver acute
      phase response. These animals offer the opportunity to study defined reductions
      in the transcriptional capacity of a widely used signaling pathway.

PMID- 14673174
TI  - Argonaute protein in the early divergent eukaryote Trypanosoma brucei: control of
      small interfering RNA accumulation and retroposon transcript abundance.
AB  - Members of the Argonaute protein family have been linked through a combination of
      genetic and biochemical studies to RNA interference (RNAi) and related phenomena.
      Here, we describe the characterization of the first Argonaute protein (AGO1) in
      Trypanosoma brucei, the earliest divergent eukaryote where RNAi has been
      described so far. AGO1 is predominantly cytoplasmic and is found in a
      ribonucleoprotein particle with small interfering RNAs (siRNAs), and this
      particle is present in a soluble form, as well as associated with polyribosomes.
      A genetic knockout of AGO1 leads to a loss of RNAi, and concomitantly, endogenous
      retroposon-derived siRNAs as well as siRNAs derived from transgenic double
      stranded RNA are reduced to almost undetectable levels. Furthermore, AGO1
      deficiency leads to an increase in retroposon transcript abundance via mechanisms
      operating at the transcriptional level and at the RNA stability level. Our
      results suggest that AGO1 function is required for production and/or
      stabilization of siRNAs and provide the first evidence for an Argonaute protein
      being involved in the regulation of retroposon transcript levels.

PMID- 14673175
TI  - Properties of ets-1 binding to chromatin and its effect on platelet factor 4 gene
      expression.
AB  - Ets-1 is important for transcriptional regulation in several hematopoietic
      lineages, including megakaryocytes. Some transcription factors bind to naked DNA
      and chromatin with different affinities, while others do not. In the present
      study we used the megakaryocyte-specific promoters platelet factor 4 (PF4), and
      glycoprotein IIb (GPIIb) as model systems to explore the properties of Ets-1
      binding to chromatin. Chromatin immunoprecipitation assays indicated that Ets-1
      binds to proximal regions in the PF4 and GPIIb promoters in vivo. In vitro and in
      vivo experiments showed that Ets-1 binding to chromatin on lineage-specific
      promoters does not require lineage-specific factors. Moreover, this binding shows
      the same order of affinity as the binding to naked DNA and does not require ATP
      dependent or Sarkosyl-sensitive factors. The effect of Ets-1 binding on promoter
      activity was examined using the PF4 promoter as a model. We identified a novel
      Ets-1 site (at -50), and a novel Sarkosyl-sensitive DNase I-hypersensitive site
      generated by Ets-1 binding to chromatin, which significantly affect PF4 promoter
      activity. Taken together, our results suggest a model by which Ets-1 binds to
      chromatin without the need for lineage-specific accessory factors, and Ets-1
      binding induces changes in chromatin and affects transactivation, which are
      essential for PF4 promoter activation.

PMID- 14673176
TI  - CoAA, a nuclear receptor coactivator protein at the interface of transcriptional
      coactivation and RNA splicing.
AB  - We have shown that steroid hormones coordinately control gene transcriptional
      activity and splicing decisions in a promoter-dependent manner. Our hypothesis is
      that a subset of hormonally recruited coregulators involved in regulation of
      promoter transcriptional activity also directly participate in alternative RNA
      splicing decisions. To gain insight into the molecular mechanisms by which
      transcriptional coregulators could control splicing decisions, we focused our
      attention on a recently identified coactivator, CoAA. This heterogeneous nuclear
      ribonucleoprotein (hnRNP)-like protein interacts with the transcriptional
      coregulator TRBP, a protein recruited to target promoters through interactions
      with activated nuclear receptors. Using transcriptional and splicing reporter
      genes driven by different promoters, we observed that CoAA mediates
      transcriptional and splicing effects in a promoter-preferential manner. We
      compared the activity of CoAA to the activity of other hnRNP-related proteins
      that, like CoAA, contain two N-terminal RNA recognition motifs (RRMs) followed by
      a C-terminal auxiliary domain and either have or have not been implicated in
      transcriptional control. By swapping either CoAA RRMs or the CoAA auxiliary
      domain with the corresponding domains of the proteins selected, we showed that
      depending on the promoter, the RRMs and the auxiliary domain of CoAA are
      differentially engaged in transcription. This contributes to the promoter
      preferential effects mediated by CoAA on RNA splicing during the course of
      steroid hormone action.

PMID- 14673177
TI  - Phorbol 12-myristate 13-acetate-induced release of the colony-stimulating factor
      1 receptor cytoplasmic domain into the cytosol involves two separate cleavage
      events.
AB  - The colony-stimulating factor 1 (CSF-1) receptor is a protein-tyrosine kinase
      that regulates cell division, differentiation, and development. In response to
      phorbol 12-myristate 13-acetate (PMA), the CSF-1 receptor is subject to
      proteolytic processing. Use of chimeric receptors indicates that the CSF-1
      receptor is cleaved at least two times, once in the extracellular domain and once
      in the transmembrane domain. Cleavage in the extracellular domain results in
      ectodomain shedding while the cytoplasmic domain remains associated with the
      membrane. Intramembrane cleavage depends on the sequence of the transmembrane
      domain and results in the release of the cytoplasmic domain. This process can be
      blocked by gamma-secretase inhibitors. The cytoplasmic domain localizes partially
      to the nucleus, displays limited stability, and is degraded by the proteosome.
      CSF-1 receptors are continuously subject to down-modulation and regulated
      intramembrane proteolysis (RIP). RIP is stimulated by granulocyte-macrophage-CSF,
      CSF-1, interleukin-2 (IL-2), IL-4, lipopolysaccharide, and PMA and may provide
      the CSF-1 receptor with an additional mechanism for signal transduction.

PMID- 14673178
TI  - The oxidized deoxynucleoside triphosphate pool is a significant contributor to
      genetic instability in mismatch repair-deficient cells.
AB  - Oxidation is a common form of DNA damage to which purines are particularly
      susceptible. We previously reported that oxidized dGTP is potentially an
      important source of DNA 8-oxodGMP in mammalian cells and that the incorporated
      lesions are removed by DNA mismatch repair (MMR). MMR deficiency is associated
      with a mutator phenotype and widespread microsatellite instability (MSI). Here,
      we identify oxidized deoxynucleoside triphosphates (dNTPs) as an important
      cofactor in this genetic instability. The high spontaneous hprt mutation rate of
      MMR-defective msh2(-/-) mouse embryonic fibroblasts was attenuated by expression
      of the hMTH1 protein, which degrades oxidized purine dNTPs. A high level of hMTH1
      abolished their mutator phenotype and restored the hprt mutation rate to normal.
      Molecular analysis of hprt mutants showed that the presence of hMTH1 reduced the
      incidence of mutations in all classes, including frameshifts, and also implicated
      incorporated 2-oxodAMP in the mutator phenotype. In hMSH6-deficient DLD-1 human
      colorectal carcinoma cells, overexpression of hMTH1 markedly attenuated the
      spontaneous mutation rate and reduced MSI. It also reduced the incidence of -G
      and -A frameshifts in the hMLH1-defective DU145 human prostatic cancer cell line.
      Our findings indicate that incorporation of oxidized purines from the dNTP pool
      may contribute significantly to the extreme genetic instability of MMR-defective
      human tumors.

PMID- 14673179
TI  - Dual effects of IkappaB kinase beta-mediated phosphorylation on p105 Fate:
      SCF(beta-TrCP)-dependent degradation and SCF(beta-TrCP)-independent processing.
AB  - Processing of the p105 NF-kappaB precursor to yield the p50 active subunit is a
      unique and rare case in which the ubiquitin system is involved in limited
      processing rather than in complete destruction of its target. The mechanisms
      involved in this process are largely unknown, although a glycine repeat in the
      middle of p105 has been identified as a processing stop signal. IkappaB kinase
      (IKK)beta-mediated phosphorylation at the C-terminal domain with subsequent
      recruitment of the SCF(beta-TrCP) ubiquitin ligase leads to accelerated
      processing and degradation of the precursor, yet the roles that the kinase and
      ligase play in each of these two processes have not been elucidated. Here we
      demonstrate that IKKbeta has two distinct functions: (i) stimulation of
      degradation and (ii) stimulation of processing. IKKbeta-induced degradation is
      dependent on SCF(beta-TrCP), which acts through multiple lysine residues in the
      IkappaBgamma domain. In contrast, IKKbeta-induced processing of p105 is beta
      transduction repeat-containing protein (beta-TrCP) independent, as it is not
      affected by expression of a dominant-negative beta-TrCP or following its
      silencing by small inhibitory RNA. Furthermore, removal of all 30 lysine residues
      from IkappaBgamma results in complete inhibition of IKK-dependent degradation but
      has no effect on IKK-dependent processing. Yet processing still requires the
      activity of the ubiquitin system, as it is inhibited by dominant-negative UbcH5a.
      We suggest that IKKbeta mediates its two distinct effects by affecting, directly
      and indirectly, two different E3s.

PMID- 14673181
TI  - Extracellular K+ accumulation: a physiological framework for fatigue during
      intense exercise.

PMID- 14673180
TI  - Chloride secretion in a morphologically differentiated human colonic cell line
      that expresses the epithelial Na+ channel.
AB  - Cell line models of colonic electrolyte transport have been extensively used
      despite lacking some of the characteristics of native tissue. While native
      colonic crypts absorb or secrete NaCl, immortalized cell lines only retain the
      secretory phenotype. In the present study we have characterized functionally and
      molecularly, vectorial fluid and electrolyte transport in the morphologically
      differentiated human colonic cell line LIM1863. LIM1863 cells form
      morphologically differentiated organoids resembling native human colonic crypts,
      which secrete fluid and electrolytes across the apical membrane into a centrally
      located lumen. Net fluid secretion was evaluated by means of morphometric
      measurement of lumens formed in LIM organoids in response to known secretagogues.
      Pharmacological profiling of the channels and transporters involved in fluid and
      electrolyte transport showed that net fluid transport requires Cl- uptake across
      the basolateral membrane through a Na(+)-K(+)-2Cl- cotransporter (NKCC1) and its
      subsequent exit across an apical cystic fibrosis transmembrane conductance
      regulator (CFTR) Cl- channel. Similar to the native colon, net Cl- secretion in
      the LIM1863 cell line is activated by cAMP-mediated agonists. Carbachol, a Ca(2+)
      mediated agonist, does not induce net Cl- secretion but modulates the cAMP
      activated response. Expression of chloride channels (CFTR and the Ca(2+)
      dependent Cl- channel, ClCa1), potassium channels (KCNN4 and KCNQ1), epithelial
      Na+ channel (ENaC) alpha, beta and gamma subunits and ion transporters (NKCC1;
      anion exchanger, AE2; Na+/H+ exchangers, NHE1-3) was detected by RT-PCR and
      Western blot in the case of ENaC. Based on this evidence we propose that LIM1863
      cells provide a unique model for studying CFTR-dependent Cl- secretion in a
      morphologically differentiated human colonic crypt cell line that also expresses
      ENaC.

PMID- 14673182
TI  - Neonatal stress alters adult breathing.

PMID- 14673183
TI  - Attenuated outward potassium currents in carotid body glomus cells of heart
      failure rabbit: involvement of nitric oxide.
AB  - It has been shown that peripheral chemoreceptor sensitivity is enhanced in both
      clinical and experimental heart failure (HF) and that impairment of nitric oxide
      (NO) production contributes to this enhancement. In order to understand the
      cellular mechanisms associated with the alterations of chemoreceptor function and
      the actions of NO in the carotid body (CB), we compared the outward K+ currents
      (IK) of glomus cells in sham rabbits with that in HF rabbits and monitored the
      effects of NO on these currents. Ik was measured in glomus cells using
      conventional and perforated whole-cell configurations. IK was attenuated in
      glomus cells of HF rabbits, and their resting membrane potentials (-34.7 +/- 1.0
      mV) were depolarized as compared with those in sham rabbits (-47.2 +/- 1.9 mV).
      The selective Ca(2+)-dependent K+ channel (KCa) blocker iberiotoxin (IbTx, 100
      nm) reduced IK in glomus cells from sham rabbits, but had no effect on IK from HF
      rabbits. In perforated whole-cell mode, the NO donor SNAP (100 microm) increased
      IK in glomus cells from HF rabbits to a greater extent than that in sham rabbits
      (P < 0.01), and IbTx inhibited the effects of SNAP. However, in conventional
      whole-cell mode, SNAP had no effect. N omega-nitro-L-arginine (L-NNA, NO synthase
      inhibitor) decreased Ik in sham rabbits but not in HF rabbits. The guanylate
      cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) inhibited the
      effect of SNAP on Ik. These results demonstrate that IK is reduced in CB glomus
      cells from HF rabbits. This effect is due mainly to the suppression of KCa
      channel activity caused by decreased availability of NO. In addition,
      intracellular cGMP is necessary for the KCa channel modulation by NO.

PMID- 14673184
TI  - Cannabinoid-induced presynaptic inhibition at the primary afferent trigeminal
      synapse of juvenile rat brainstem slices.
AB  - Systemic or intraventricular administration of cannabinoids causes analgesic
      effects, but relatively little is known for their cellular mechanism. Using
      brainstem slices with the mandibular nerve attached, we examined the effect of
      cannabinoids on glutamatergic transmission in superficial trigeminal caudal
      nucleus of juvenile rats. The exogenous cannabinoid receptor agonist WIN 55,212-2
      (WIN), as well as the endogenous agonist anandamide, hyperpolarized trigeminal
      caudal neurones and depressed the amplitude of excitatory postsynaptic potentials
      (EPSPs) or currents (EPSCs) monosynaptically evoked by stimulating mandibular
      nerves in a concentration-dependent manner. The inhibitory action of WIN was
      blocked or fully reversed by the CB1 receptor antagonist SR 141716A. WIN had no
      effect on the amplitude of miniature excitatory postsynaptic currents (mEPSCs)
      recorded in the presence of tetrodotoxin or cadmium. The inhibitory effect of WIN
      on EPSCs was greater for those with longer synaptic latency, suggesting that
      cannabinoids have a stronger effect on C-fibre EPSPs than on Adelta-fibre EPSPs.
      Ba2+ (100 microm) blocked the hyperpolarizing effect of cannabinoids, but did not
      affect their inhibitory effect on EPSPs. The N-type Ca2+ channel blocker omega
      conotoxin GVIA (omega-CgTX) occluded the WIN-mediated presynaptic inhibition,
      whereas the P/Q-type Ca2+ channel blocker omega-agatoxin TK (omega-Aga) had no
      effect. These results suggest that cannabinoids preferentially activate CB1
      receptors at the nerve terminal of small-diameter primary afferent fibres. Upon
      activation, CB1 receptors may selectively inhibit presynaptic N-type Ca2+
      channels and exocytotic release machinery, thereby attenuating the transmitter
      release at the trigeminal nociceptive synapses.

PMID- 14673185
TI  - Cholecystokinin activates CCKB receptors to excite cells and depress EPSCs in the
      rat rostral nucleus accumbens in vitro.
AB  - The peptide cholecystokinin (CCK) is abundant in the rat nucleus accumbens (NAc).
      Although it is colocalized with dopamine (DA) in afferent terminals in this
      region, neurochemical and behavioural reports are equally divided as to whether
      CCK enhances or diminishes DA's actions in this nucleus. To better understand the
      role of this peptide in the physiology of the NAc, we examined the effects of CCK
      on excitatory synaptic transmission and tested whether these are dependent on DA
      and/or other neuromodulators. Using whole-cell recording in rat forebrain slices
      containing the NAc, we show that sulphated CCK octapeptide (CCK-8S), the
      endogenously active neuropeptide, consistently depolarized cells and depressed
      evoked excitatory postsynaptic currents (EPSCs) in the rostral NAc. It caused a
      reversible, dose-dependent decrease in evoked EPSC amplitude that was accompanied
      by an increase in the decay constant of the EPSC but with no apparent change in
      paired pulse ratio. It was mimicked by unsulphated CCK-8 (CCK-8US), a CCK(B)
      receptor-selective agonist, and blocked by LY225910, a CCK(B) receptor-selective
      antagonist. Both CCK-8S and CCK-8US induced an inward current with a reversal
      potential around -90 mV that was accompanied by an increase in input resistance
      and action potential firing. The CCK-8S-induced EPSC depression was slightly
      reduced in the presence of SCH23390 but not in the presence of sulpiride or 8
      cyclopentyltheophylline. By contrast, it was completely blocked by CGP55845, a
      potent GABA(B) receptor-selective antagonist. These results indicate that CCK
      excites NAc cells directly while depressing evoked EPSCs indirectly, mainly
      through the release of GABA.

PMID- 14673186
TI  - Maternal melatonin selectively inhibits cortisol production in the primate fetal
      adrenal gland.
AB  - We tested the hypothesis that in primates, maternal melatonin restrains fetal and
      newborn adrenal cortisol production. A functional G-protein-coupled MT1 membrane
      bound melatonin receptor was detected in 90% gestation capuchin monkey fetal
      adrenals by (a) 2-[(125)I] iodomelatonin binding (K(d), 75.7 +/- 6.9 pm; B(max),
      2.6 +/- 0.4 fmol (mg protein)(-1)), (b) cDNA identification, and (c) melatonin
      inhibition of adrenocorticotrophic hormone (ACTH)- and corticotrophin-releasing
      hormone (CRH)-stimulated cortisol but not of dehydroepiandrosterone sulphate
      (DHAS) production in vitro. Melatonin also inhibited ACTH-induced 3beta
      hydroxysteroid dehydrogenase mRNA expression. To assess the physiological
      relevance of these findings, we next studied the effect of chronic maternal
      melatonin suppression (induced by exposure to constant light during the last
      third of gestation) on maternal plasma oestradiol during gestation and on plasma
      cortisol concentration in the 4- to 6-day-old newborn. Constant light suppressed
      maternal melatonin without affecting maternal plasma oestradiol concentration,
      consistent with no effect on fetal DHAS, the precursor of maternal oestradiol.
      However, newborns from mothers under constant light condition had twice as much
      plasma cortisol as newborns from mothers maintained under a normal light-dark
      schedule. Newborns from mothers exposed to chronic constant light and daily
      melatonin replacement had normal plasma cortisol concentration. Our results
      support a role of maternal melatonin in fetal and neonatal primate cortisol
      regulation.

PMID- 14673187
TI  - Activation and integration of bilateral GABA-mediated synaptic inputs in neonatal
      rat sympathetic preganglionic neurones in vitro.
AB  - The role of GABA receptors in synaptic transmission to neonatal rat sympathetic
      preganglionic neurones (SPNs) was investigated utilizing whole-cell patch clamp
      recording techniques in longitudinal and transverse spinal cord slice
      preparations. In the presence of glutamate receptor antagonists (NBQX, 5 microm
      and D-APV, 10 microm), electrical stimulation of the ipsilateral or contralateral
      lateral funiculi (iLF and cLF, respectively) revealed monosynaptic inhibitory
      postsynaptic potentials (IPSPs) in 75% and 65% of SPNs, respectively. IPSPs were
      sensitive to bicuculline (10 microM) in all neurones tested and reversed polarity
      around -55 mV, the latter indicating mediation via chloride conductances. In
      three neurones IPSPs evoked by stimulation of the iLF (n = 1) or cLF (n = 2) were
      partly sensitive to strychnine (2 microM). The expression of postsynaptic GABA(A)
      and GABA(B) receptors were confirmed by the sensitivity of SPNs to agonists, GABA
      (2 mm), muscimol (10-100 microM) or baclofen (10-100 microM), in the presence of
      TTX, each of which produced membrane hyperpolarization in all SPNs tested.
      Muscimol-induced responses were sensitive to bicuculline (1-10 microM) and
      SR95531 (10 microM) and baclofen-induced responses were sensitive to 2-hydroxy
      saclofen (100-200 microM) and CGP55845 (200 nM). The GABA(C) receptor agonist
      CACA (200 microM) was without significant effect on SPNs. These results suggest
      that SPNs possess postsynaptic GABA(A) and GABA(B) receptors and that subsets of
      SPNs receive bilateral GABAergic inputs which activate GABA(A) receptors, coupled
      to a chloride conductance. At resting or holding potentials close to threshold
      either single or bursts (10-100 Hz) of IPSPs gave rise to a rebound excitation
      and action potential firing at the termination of the burst. This effect was
      mimicked by injection of small (10-20 pA) rectangular-wave current pulses, which
      revealed a time-dependent, Cs(+)-sensitive inward rectification and rebound
      excitation at the termination of the response to current injection. Synaptic
      activation of a rebound excitation mediated by a time-dependent inward
      rectification expressed intrinsically by SPNs may provide a novel mechanism
      enabling SPNs to be entrained to rhythms driven from the brainstem or higher
      centres.

PMID- 14673188
TI  - Actions of noradrenaline on substantia gelatinosa neurones in the rat spinal cord
      revealed by in vivo patch recording.
AB  - To elucidate the mechanisms of antinociception mediated by the descending
      noradrenergic pathway in the spinal cord, the effects of noradrenaline (NA) on
      noxious synaptic responses of substantia gelatinosa (SG) neurones, and
      postsynaptic actions of NA were investigated in rats using an in vivo whole-cell
      patch-clamp technique. Under urethane anaesthesia, the rat was fixed in a
      stereotaxic apparatus after the lumbar spinal cord was exposed. In the current
      clamp mode, pinch stimuli applied to the ipsilateral hindlimb elicited a barrage
      of EPSPs, some of which initiated an action potential. Perfusion with NA onto the
      surface of the spinal cord hyperpolarized the membrane (5.0-9.5 mV) and
      suppressed the action potentials. In the voltage-clamp mode (V(H), -70 mV), the
      application of NA produced an outward current that was blocked by Cs(+) and GDP
      beta-S added to the pipette solution and reduced the amplitude of EPSCs evoked by
      noxious stimuli. Under the blockade of postsynaptic actions of NA, a reduction of
      the evoked and spontaneous EPSCs of SG neurones was still observed, thus
      suggesting both pre- and postsynaptic actions of NA. The NA-induced outward
      currents showed a clear dose dependency (EC(50), 20 microM), and the reversal
      potential was -88 mV. The outward current was mimicked by an alpha(2)
      adrenoceptor agonist, clonidine, and suppressed by an alpha(2)-adrenoceptor
      antagonist, yohimbine, but not by alpha(1)- and beta-antagonists. These findings
      suggest that NA acts on presynaptic sites to reduce noxious stimuli-induced
      EPSCs, and on postsynaptic SG neurones to induce an outward current by G-protein
      mediated activation of K(+) channels through alpha(2)-adrenoceptors, thereby
      producing an antinociceptive effect.

PMID- 14673189
TI  - Sex differences in the alterations of Na(+), K(+)-ATPase following ischaemia
      reperfusion injury in the rat kidney.
AB  - Postischaemic acute renal failure (ARF) is influenced by sex. Na(+), K(+)-ATPase
      (NKA) plays a crucial role in the pathogenesis of postischaemic ARF. We tested
      the impact of sex on mRNA, protein expression, cellular distribution and enzyme
      activity of NKA following renal ischaemia-reperfusion (I-R) injury. The left
      renal pedicle of uninephrectomized female (F) and male (M) Wistar rats was
      clamped for 55 min followed by 2 h (T2) and 16 h (T16) of reperfusion.
      Uninephrectomized, sham-operated F and M rats served as controls (n= 6 per
      group). Blood urea nitrogen, serum creatinine and renal histology were evaluated
      to detect the severity of postischaemic ARF. mRNA expression of NKA alpha1 and
      beta1 subunits were detected by RT-PCR. The effect of I-R on cellular
      distribution was compared by Triton X-100 extraction. Cellular proteins were
      divided into Triton-insoluble and Triton-soluble fractions and assessed by
      Western blot. NKA enzyme activity was also determined. After the ischaemic insult
      blood urea nitrogen and serum creatinine were higher and renal histology showed
      more rapid progression in M versus F (P < 0.05). mRNA expression of the NKA
      alpha1 subunit decreased in I-R groups versus controls, but was higher in F
      versus M both in control and I-R groups (P < 0.05). However, protein levels of
      the NKA alpha1 subunit in total tissue homogenate did not differ in controls, but
      were higher in F versus M in I-R groups (P < 0.05). Triton X-100 extractability
      was lower in F versus M at T16 (P < 0.05). NKA enzyme activity was the same in
      controls, but was higher in F versus M in I-R groups (T2: 14.9 +/- 2.3 versus
      9.15 +/- 2.21 U) (T16: 11.7 +/- 4.1 versus 5.65 +/- 2.3 U; P < 0.05). mRNA and
      protein expression of the NKA beta1 subunit did not differ between F and M in any
      of the protocol. We concluded that NKA is more protected from the detrimental
      effects of postischaemic injury in females. Higher mRNA and protein expression of
      the NKA alpha1 subunit and higher enzyme activity might be additional
      contributing factors to the improved postischaemic renal function of female rats.

PMID- 14673190
TI  - Synapse-specific mGluR1-dependent long-term potentiation in interneurones
      regulates mouse hippocampal inhibition.
AB  - Hippocampal CA1 inhibitory interneurones control the excitability and
      synchronization of pyramidal cells, and participate in hippocampal synaptic
      plasticity. Pairing theta-burst stimulation (TBS) with postsynaptic
      depolarization, we induced long-term potentiation (LTP) of putative single-fibre
      excitatory postsynaptic currents (EPSCs) in stratum oriens/alveus (O/A)
      interneurones of mouse hippocampal slices. LTP induction was absent in
      metabotropic glutamate receptor 1 (mGluR1) knockout mice, was correlated with the
      postsynaptic presence of mGluR1a, and required a postsynaptic Ca2+ rise. Changes
      in paired-pulse facilitation and coefficient of variation indicated that LTP
      expression involved presynaptic mechanisms. LTP was synapse specific, occurring
      selectively at synapses modulated by presynaptic group II, but not group III,
      mGluRs. Furthermore, the TBS protocol applied in O/A induced a long-term increase
      of polysynaptic inhibitory responses in CA1 pyramidal cells, that was absent in
      mGluR1 knockout mice. These results uncover the mechanisms of a novel form of
      interneurone synaptic plasticity that can adaptively regulate inhibition of
      hippocampal pyramidal cells.

PMID- 14673191
TI  - Respiratory muscle injury, fatigue and serum skeletal troponin I in rat.
AB  - To evaluate injury to respiratory muscles of rats breathing against an
      inspiratory resistive load, we measured the release into blood of a myofilament
      protein, skeletal troponin I (sTnI), and related this release to the time course
      of changes in arterial blood gases, respiratory drive (phrenic activity), and
      pressure generation. After approximately 1.5 h of loading, hypercapnic
      ventilatory failure occurred, coincident with a decrease in the ratio of
      transdiaphragmatic pressure to integrated phrenic activity (P(di)/ integral Phr)
      during sighs. This was followed at approximately 1.9 h by a decrease in the
      P(di)/ integral Phr ratio during normal loaded breaths (diaphragmatic fatigue).
      Loading was terminated at pump failure (a decline of P(di) to half of steady
      state loaded values), approximately 2.4 h after load onset. During 30 s
      occlusions post loading, rats generated pressure profiles similar to those during
      occlusions before loading, with comparable blood gases, but at a higher neural
      drive. In a second series of rats, we tested for sTnI release using Western blot
      direct serum analysis of blood samples taken before and during loading to pump
      failure. We detected only the fast isoform of sTnI, release beginning midway
      through loading. Differential detection with various monoclonal antibodies
      indicated the presence of modified forms of fast sTnI. The release of fast sTnI
      is consistent with load-induced injury of fast glycolytic fibres of inspiratory
      muscles, probably the diaphragm. Characterization of released fast sTnI may
      provide insights into the molecular basis of respiratory muscle dysfunction; fast
      sTnI may also prove useful as a marker of impending respiratory muscle fatigue.

PMID- 14673192
TI  - Basolateral Na+-dependent HCO3- transporter NBCn1-mediated HCO3- influx in rat
      medullary thick ascending limb.
AB  - The electroneutral Na(+)-dependent HCO3- transporter NBCn1 is strongly expressed
      in the basolateral membrane of rat medullary thick ascending limb cells (mTAL)
      and is up-regulated during NH4(+)-induced metabolic acidosis. Here we used in
      vitro perfusion and BCECF video-imaging of mTAL tubules to investigate functional
      localization and regulation of Na(+)-dependent HCO3- influx during NH4(+)-induced
      metabolic acidosis. Tubule acidification was induced by removing luminal Na+
      (DeltapHi: 0.88 +/- 0.11 pH units, n = 10). Subsequently the basolateral
      perfusion solution was changed to CO2/HCO3- buffer with and without Na+.
      Basolateral Na(+)-H+ exchange function was inhibited with amiloride. Na(+)
      dependent HCO3- influx was determined by calculating initial base flux of Na(+)
      mediated re-alkalinization. In untreated animals base flux was 8.4 +/- 0.9 pmol
      min(-1) mm(-1). A 2.4-fold increase of base flux to 21.8 +/- 3.2 pmol min(-1) mm(
      1) was measured in NH4(+)-treated animals (11 days, n = 11). Na(+)-dependent re
      alkalinization was significantly larger when compared to control animals (0.38 +/
      0.03 versus 0.22 +/- 0.02 pH units, n = 10). In addition, Na(+)-dependent HCO3-
      influx was of similar magnitude in chloride-free medium and also up-regulated
      after NH4+ loading. Na(+)-dependent HCO3- influx was not inhibited by 400 microm
      DIDS. A strong up-regulation of NBCn1 staining was confirmed in immunolabelling
      experiments. RT-PCR analysis revealed no evidence for the Na(+)-dependent HCO3-
      transporter NBC4 or the two Na(+)-dependent CI-/HCO3- exchangers NCBE and NDCBE.
      These data strongly indicate that rat mTAL tubules functionally express
      basolateral DIDS-insensitive NBCn1. Function and protein are strongly up
      regulated during NH4(+)-induced metabolic acidosis. We suggest that NBCn1
      mediated basolateral HCO3- influx is important for basolateral NH3 exit and thus
      NH4+ excretion by means of setting pHi to a more alkaline value.

PMID- 14673193
TI  - A newborn rat model for the study of cerebral hemodynamics by near-infrared
      spectroscopy and laser-Doppler flowmetry in the immature brain.
AB  - An animal model for the study of cerebrovascular physiology in the immature brain
      was developed. Twelve 3- to 5-day-old rat pups were maintained on spontaneous
      breathing under light anesthesia for either 1 or 2 h. Transcutaneous carbon
      dioxide tension and arterial oxygen saturation were monitored. Continuous
      infusion of doxapram limited respiratory acidosis. Cerebral blood flow (CBF) and
      volume (CBV) could be monitored by near-infrared spectroscopy (NIRS) and laser
      Doppler flowmetry (LDF) in spite of some movement artifacts. CBV and CBF were 6.0
      +/- 0.3 SE ml/100 g and 36.3 +/- 3.1 SE ml/100 g/min, respectively, and remained
      stable during the study. Cerebrovascular responses, as monitored by LDF and NIRS,
      to hypoxic and hypercapnic gas mixtures were consistent.

PMID- 14673194
TI  - Tactile foveation in the star-nosed mole.
AB  - Star-nosed moles have a specialized somatosensory system with 22 mechanosensory
      appendages surrounding the nostrils. A pair of appendages (the 11th pair on the
      ventral midline) acts as the tactile fovea and is used for detailed
      investigations. Here we used a high speed video camera to document movements of
      the star while moles searched for small prey items. Mole foraging behavior was
      very fast; the star, which is just over a centimeter in diameter, was touched to
      different areas of the environment approximately 13 times per second. This
      suggests that a mole foraging without interruption could potentially investigate
      46,000 cm2 of surface area per hour. In 100% of 526 trials in which prey was
      identified and eaten, star-nosed moles made rapid, saccadic movements of the star
      to investigate the contacted prey with the foveal appendages. The movements of
      the star were similar to visual saccades in other species. Maximum velocity of
      the star during saccades was approximately 40 cm/s, and most saccades were
      between 30 and 60 ms in duration. As in the primate visual system, small
      corrective saccades were often needed to accurately foveate. We quantified the
      number of contacts different appendages made with prey items of various sizes
      during each encounter and compared this distribution to a previously proposed
      simulation of star movements during prey encounters. The behavior pattern and the
      simulation produced similar distributions of contact between the appendages and
      prey, and both distributions were closely correlated with the degree of cortical
      magnification of the appendage representations in primary somatosensory cortex
      (S1).

PMID- 14673195
TI  - A strong correlation exists between the distribution of retinal ganglion cells
      and nose length in the dog.
AB  - The domestic dog, CANIS LUPUS FAMILIARIS, is a subspecies of the gray wolf, CANIS
      LUPUS, with almost identical mitochondrial DNA. The dog is the most diverse
      species on earth, with skull length varying between 7 and 28 cm whereas the wolf
      skull is around 30 cm long. However, eye size in dogs does not appear to vary as
      much. For example, small dogs such as the chihuahua appear to have very large
      eyes in proportion to the skull. Our aim was to examine eye size and retinal cell
      numbers and distribution to determine whether the dog eye exhibits as much
      variation as the skull. We found a correlation between eye radius and skull
      dimensions. However, the most surprising finding was that the distribution of
      ganglion cells in the eye varied tremendously from a horizontally aligned visual
      streak of fairly even density across the retina (as seen in the wolf) to a strong
      area centralis with virtually no streak (for example, as observed in a pug from
      the current series). This variation in ganglion cell density within a single
      species is quite unique. Intriguingly, the ratio of peak ganglion cell density in
      the area centralis to visual streak was highly negatively correlated with skull
      length (r = -0.795, n = 22) and positively correlated with cephalic index (r =
      0.687, n = 22). The orientation of eyelid aperture was also correlated with
      cephalic index (r = 0.648, n = 22). Therefore, the genetic manipulation of
      selective breeding, which has produced an abnormal shortening of the skull and
      eyelids with less lateral apertures, has also produced a considerably more
      pronounced area centralis in the dog.

PMID- 14673196
TI  - A possible stimulatory effect of FMRFamide on neural nitric oxide production in
      the central nervous system of Helix lucorum L.
AB  - The anatomical and functional relationship between neurons expressing nitric
      oxide (NO) synthase and molluscan cardioexcitatory (FMRFamide)-like neuropeptides
      was studied in the central ganglia of Helix lucorum (Pulmonata, Gastropoda),
      applying NADPHdiaphorase (NADPHd) histochemistry to visualize NO synthase and
      immunocytochemistry to demonstrate FMRFamide (FMRFa) at the light microscopic
      level. The NO production of the ganglia was detected by the colorimetric Griess
      determination of nitrite, a breakdown product of NO. Effects of the NO synthase
      substrate amino acid L-arginine, the NO synthase inhibitor Nomega-nitro-L
      arginine (NOARG), synthetic FMRFa and the FMRFa sensitive ion channel blocker
      amiloride hydrochloride on nitrite production were also tested. NADPHd reaction
      labeled nerve cells and fibers in the procerebra, mesocerebra and metacerebra
      within the cerebral ganglia, and cell clusters in the postcerebral ganglia. FMRFa
      immunolabeling could be observed within subpopulations of NADPHd positive cells
      and in pericellular varicose fibers surrounding NADPHd stained neurons. Nitrite
      production of the ganglia was stimulated by L-arginine (10- 20 mM) but was
      decreased by NOARG (1-2 mM). Synthetic FMRFa (0.830-3.340 mM) increased the
      nitrite production in a dose dependent manner, but was ineffective in the
      presence of NOARG. Amiloride hydrochloride (7.890 mM) reduced the FMRFa evoked
      nitrite production in all ganglia. This is the first description of an anatomical
      relationship between putative NO producing and FMRFa containing cells, suggesting
      a possible regulatory role of FMRFa in the NO mediated signaling in an
      invertebrate nervous system.

PMID- 14673197
TI  - Evidence for a novel gonadotropin-releasing hormone in hypothalamic and forebrain
      areas in songbirds.
AB  - One or more of three distinct forms of gonadotropin-releasing hormones (GnRHs),
      has been found in all vertebrates studied. Birds are known to contain two types
      of GnRH, chicken GnRH-I and -II (cGnRH-I and -II), but to date nobody has
      investigated the possibility of the presence of lamprey GnRH-III in birds. Thus,
      our objective was to investigate the presence and distribution of immunoreactive
      lamprey (ir-lamprey) GnRH-III in hypothalamic and forebrain areas in house
      sparrows (Passer domesticus) and Gambel's white-crowned sparrows (Zonotrichia
      leucophrys gambelii). In addition to its distribution in the CNS, we investigated
      whether or not exogenous lamprey GnRH-III peptide could elicit luteinizing
      hormone (LH) release in vivo. This study presents two novel findings: 1) The
      widespread presence in the central nervous system of an immunoreactive third GnRH
      in birds that is clearly hypophysiotropic and has gonadotropin-releasing
      capabilities. Intravenous injection of 100 ng lamprey-GnRH-III peptide elicited a
      rapid rise in circulating luteinizing hormone as compared to controls. This third
      GnRH, ir-lamprey GnRH-III, likely has multiple functions, as suggested by its
      widespread distribution. 2) Ir-lamprey GnRH-III is present in abundance in
      telencephalic areas, including the hippocampal formation and the song control
      system. In no vertebrate has a GnRH been localized in these 'higher' control
      regions before. The fact that ir-lamprey-GnRH-III is present in auditory
      processing areas (higher vocal center, or HVc, area X, caudomedial neostriatum)
      and song-producing areas (HVc, robust nucleus of the neostriatum, or RA) suggests
      a direct way in which auditory processing and song production can affect
      circulating gonadotropins.

PMID- 14673198
TI  - Brain size scaling and body composition in mammals.
AB  - Brain size scales with body size across large groups of animals, but exactly why
      this should be the case has not been resolved. It is generally assumed that body
      size is a general proxy for some more important or specific underlying variable,
      such as metabolic resources available, surface area of the body, or total muscle
      mass (which is more extensively innervated than is, e.g., adipose tissue). The
      present study tests whether brain size in mammals scales more closely with muscle
      mass (and other components of lean body mass) than with total fat. Felsenstein's
      independent comparisons method was used to control for phylogenetic effects on
      body composition in organ weight data taken from a previously published
      comparative sample of 39 species in 8 different orders of mammals, all collected
      and processed by the same researchers. The analysis shows that the size of the
      central nervous system (CNS) is more closely associated with components of fat
      free weight than it is to fat weight. These results suggest a possible
      explanation for why metabolic resources and brain size both share the same
      general relationship with body size across mammals. They also suggest that some
      measure of lean body mass is a more appropriate scaling parameter for comparing
      brain size across species than is overall body weight.

PMID- 14673199
TI  - Serous oligocystic adenoma of the pancreas.
AB  - Cystic neoplasms of the pancreas are uncommon lesions but are becoming
      increasingly prevalent. Herein we report a case of an oligolocular cystic lesion
      in the head of the pancreas in a young female that had undergone a
      cystenteroanastomosis 10 years ago. She underwent a duodenopancreatectomy with an
      uneventful recovery. The histology showed a serous oligocystic adenoma of the
      pancreas and the immunohistochemistry study confirmed the diagnosis. There is no
      sign of recurrence after the surgery. The role of pre-operative diagnosis based
      on tomographic, echoendoscopy and fine needle aspiration are discussed.

PMID- 14673200
TI  - Differentiation of acinar cells into acinoductular cells in regenerating rat
      pancreas.
AB  - BACKGROUND/AIMS: Several lines of experimental data suggest that acinar cells
      have the potential to differentiate into ductular-like cells, and these newly
      formed acinoductular cells may act as (facultative) stem cells. The purpose of
      this study was to test this hypothesis in a model of pancreatic regeneration in
      rats. METHODS: In the current study, using a 90% pancreatectomy as a rat model
      for pancreatic regeneration, we serially examined the pancreatic tissues in a
      time-dependent manner by conventional histology and immunostaining. Cell
      proliferation was assessed by in vivo bromodeoxyuridine (BrdU) labeling. RESULTS:
      By 24 h after surgery, acini showed depleted granules with more dilated lumens
      (acinar ectasia). By day 2, focal regions of regeneration appeared which were
      separated by fibrosis and composed of ductular-like cells (tubular complexes) and
      acinar cells with dilated lumina. Double immunofluorescent staining revealed that
      both amylase and CK19 were positive in the same cells localized to the focus of
      regeneration from the animals on day 2, the phenotype of cells from those regions
      apparently reverted to acinar cells, and the regions completely disappeared by
      day 7. By 48 h after surgery, the number of BrdU-positive cells increased 4.3
      fold in ductular cells, and 2.5-fold in acinar cells compared with control
      tissue. CONCLUSION: Acinar cells through acinoductular metaplasia may be a source
      of pancreatic regeneration.

PMID- 14673201
TI  - Signal transduction, calcium and acute pancreatitis.
AB  - Evidence consistently suggests that the earliest changes of acute pancreatitis
      are intracellular, the hallmark of which is premature intracellular activation of
      digestive zymogens, accompanied by disruption of normal signal transduction and
      secretion. Principal components of physiological signal transduction include
      secretagogue-induced activation of G-protein-linked receptors, followed by
      generation of inositol 1,4,5-trisphosphate, nicotinic acid adenine dinucleotide
      phosphate and cyclic ADP-ribose. In response, calcium is released from
      endoplasmic reticulum terminals within the apical, granular pole of the cell,
      where calcium signals are usually contained by perigranular mitochondria, in turn
      responding by increased metabolism. When all three intracellular messengers are
      administered together, even at threshold concentrations, dramatic potentiation
      results in sustained, global, cytosolic calcium elevation. Prolonged, global
      elevation of cytosolic calcium is also induced by hyperstimulation, bile salts,
      alcohol and fatty acid ethyl esters, and depends on continued calcium entry into
      the cell. Such abnormal calcium signals induce intracellular activation of
      digestive enzymes, and of nuclear factor kappaB, as well as the morphological
      changes of acute pancreatitis. Depletion of endoplasmic reticulum calcium and
      mitochondrial membrane potential may contribute to further cell injury. This
      review outlines current understanding of signal transduction in the pancreas, and
      its application to the pathophysiology of acute pancreatitis.

PMID- 14673202
TI  - The structural perspective on CDK5.
AB  - Cyclin-dependent kinase 5 (CDK5) plays an essential role in the development of
      the central nervous system during mammalian embryogenesis. In the adult, CDK5 is
      required for the maintenance of neuronal architecture. Its deregulation has
      profound cytotoxic effects and has been implicated in the development of
      neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral
      sclerosis. In this review, we concentrate on the regulation of CDK5 activity,
      privileging a structural perspective based on a decade of structural analyses of
      different members of the CDK family, including CDK2 and CDK5. We review the
      activation mechanism of CDK5 and discuss its differences and similarities with
      that of CDK2 and of the other members of the CDK family.

PMID- 14673203
TI  - Cyclin-dependent kinase 5 and neuronal migration in the neocortex.
AB  - The cyclin-dependent kinase 5 (Cdk5) plays an important role in the proper
      establishment of neocortical layers. Over the past several years, key molecular
      targets of Cdk5 have been identified that show intriguing connections to the
      adhesional and cytoskeletal components of cell movement. This molecular knowledge
      about Cdk5 signaling has begun to translate into an understanding of how Cdk5
      regulates the cellular physiology of neocortical layer formation. Together with
      recent progress on the signaling relationship between Cdk5 and Reelin, the other
      key protein involved in neocortical layer formation, and their relationship to
      migration modes, research on understanding neocortical layer formation has
      arrived at a most promising crossroad.

PMID- 14673204
TI  - Cdk5: a new player at synapses.
AB  - Cdk5 is a member of the cyclin-dependent kinase family. Unlike other conventional
      Cdks that are major regulators of eukaryotic cell cycle progression, Cdk5
      displays diverse functions in neuronal as well as non-neuronal tissues. In
      particular, accumulating evidence points to the roles of this kinase in CNS
      development and other cellular processes. In this article, we summarize the
      functional roles of Cdk5 pertaining to the formation and functions of synapse, a
      specialized structure for the fundamental functions of neurons.

PMID- 14673205
TI  - Role of Cdk5 in neuronal signaling, plasticity, and drug abuse.
AB  - Functional and structural neuronal plasticity are mediated by a complex network
      of biochemical signal transduction pathways that control the strength of specific
      synapses and the formation of new synapses de novo. The neuronal protein kinase
      Cdk5 has been implicated as being involved in numerous aspects of both functional
      and structural plasticity through its regulation of signal transduction pathways.
      In this review the findings of a number of studies are summarized that have
      advanced our understanding of how Cdk5 may be involved in these processes. We
      focus on the modulation of protein phosphatase activity in both the hippocampus
      and basal ganglia, and review findings that indicate Cdk5 is likely to regulate
      neuronal plasticity in these brain regions. Studies showing involvement of Cdk5
      in reward and motor-based plasticity, which are thought to underlie drug abuse,
      are discussed.

PMID- 14673206
TI  - Cdk5: a novel role in learning and memory.
AB  - Learning and memory are processes by which organisms acquire, retain and retrieve
      information. They result in modifications of behavior in response to new or
      previously encountered stimuli thereby enabling adaptation to a permanently
      changing environment. Protein phosphorylation has long been known to play a key
      role in triggering synaptic changes underlying learning and memory. Although
      intracellular phosphorylation and dephosphorylation is orchestrated by a complex
      network of interactions between a number of protein kinases and phosphatases,
      significant advances in the understanding of neuronal mechanisms underlying
      learning and memory have been achieved by investigating the actions of individual
      molecules under defined experimental conditions, brain areas, neuronal cells and
      their subcellular compartments. On the basis of these approaches, the cyclic AMP
      protein kinase (PKA), protein kinase C (PKC) and extracellularly regulated
      protein kinases 1 and 2 (Erk-1/2) have been identified as the core signaling
      pathways in memory consolidation. Here we review recent findings demonstrating an
      important novel role for Cdk5 in learning and memory. We suggest that some of the
      well-characterized roles of Cdk5 during neurodevelopmental processes, such as
      interactions with distinct cytoplasmic and synaptic target molecules, may be also
      involved in synaptic plasticity underlying memory consolidation within the adult
      central nervous system.

PMID- 14673207
TI  - Role of cdk5 in the pathogenesis of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by two pathological hallmarks, namely,
      senile plaques and neurofibrillary tangles (NFTs). The former are mainly composed
      of amyloid-beta peptides (Abeta) while the latter consists mainly of filaments of
      hyperphosphorylated tau. Cyclin-dependent kinase 5 (cdk5) has been implicated not
      only in the tangle pathology, but recent data also implicate cdk5 in the
      generation of Abeta peptides. Since both Abeta peptides and NFTs are believed to
      play a role in neurodegeneration in AD, this proline-directed serine/threonine
      protein kinase is likely to contribute to the pathogenesis of AD. In vitro and in
      vivo animal data demonstrate the ability of cdk5 to induce phosphorylation and
      aggregation of tau, and NFT deposition and neurodegeneration. Findings from AD
      brain samples also show an elevated cdk5 activity and conditions that support the
      activation of cdk5. Evidence for the role of cdk5 in regulating Abeta production
      is just emerging. The mechanisms for this potentially damaging activity of cdk5
      are largely unknown although amyloid precursor protein and presenilin-1 are both
      cdk5 substrates.

PMID- 14673208
TI  - Cyclin-dependent kinase 5 in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis is a neurological disorder that selectively affects
      motor neurons of brain and spinal cord. Emerging evidence indicates an
      involvement of the serine/threonine-cyclin-dependent kinase 5 (Cdk5) in the
      pathogenesis. Deregulation of Cdk5 by its truncated co-activators, p25 and p29,
      contributes to neurodegeneration by altering the phosphorylation state of
      cytosolic and cytoskeletal proteins and, possibly, through the induction of cell
      cycle regulators. The present paper reviews these findings and proposes new
      perspectives to decipher the mechanisms of neurodegeneration in amyotrophic
      lateral sclerosis induced by Cdk5.

PMID- 14673209
TI  - The regulation of cyclin-dependent kinase 5 activity through the metabolism of
      p35 or p39 Cdk5 activator.
AB  - Cyclin-dependent kinase 5 (Cdk5) displays kinase activity predominantly in post
      mitotic neurons and its physiological roles are unrelated to cell cycle
      progression. Cdk5 is activated by its binding to a neuron-specific activator, p35
      or p39. The protein amount of p35 or p39 is a primary determinant of the Cdk5
      activity in neurons, with the amount of p35 or p39 being determined by its
      synthesis and degradation. The expression of p35 is induced in differentiated
      neurons and is enhanced by extracellular stimuli such as neurotrophic factors or
      extracellular matrix molecules, specifically those acting on the ERK/Erg pathway.
      p35 is a short-lived protein and its degradation determines the life span.
      Degradation is mediated by the ubiquitin/proteasome system, similar to that for
      cyclins in proliferating cells. Autophosphorylation of p35 by Cdk5 is a signal
      for ubiquitination/degradation, and the degradation of p35 is triggered by
      glutamate treatment in cultured neurons. p35 is cleaved to p25 by calpain at the
      time of neuronal cell death, and this limited cleavage is suggested to be the
      cause of neurodegenerative diseases such as Alzheimer's disease. Active Cdk5
      changes the cellular localization by cleavage of p35 to p25; p35/Cdk5 is
      associated with membrane or cytoskeletons, but p25/Cdk5 is a soluble protein.
      Cleavage also increases the life span of p25 and changes the activity or
      substrate specificity of Cdk5. p25/Cdk5 shows higher phosphorylating activity to
      tau than p35/Cdk5 in a phosphorylation site-specific manner. Phosphorylation of
      p35 suppresses cleavage by calpain. Thus, phosphorylation of p35 modulates its
      proteolytic pattern, stimulates proteasomal degradation and suppresses calpain
      cleavage. Phosphorylation is age dependent, as p35 is phosphorylated in foetal
      brains, but unphosphorylated in adult brains. Therefore, foetal phosphorylated
      p35 is turned over rapidly, whereas adult unphosphorylated p35 has a long life
      and is easily cleaved to p25 when calpain is activated. p39 is also a short-lived
      protein and cleaved to the N-terminal truncation form of p29 by calpain. How the
      metabolism of p39 is regulated, however, is a future problem to be investigated.

PMID- 14673210
TI  - Protein-protein interactions in Cdk5 regulation and function.
AB  - Cdk5 is a unique member of the cyclin-dependent kinase (Cdk) family of small
      protein kinases. In association with its neuron-specific activator p35 or p39,
      Cdk5 displays many regulatory properties distinct from other Cdks. A growing body
      of evidence has suggested that Cdk5-p35 has important implications in a variety
      of neuronal activities occurring in the central nervous system. In brain, Cdk5
      p35 appears to exist as large molecular complexes with other proteins, and
      protein-protein interactions appear to be a molecular principle for Cdk5-p35 to
      conduct its physiological functions. Over the past decade, a number of proteins
      have been identified to associate with Cdk5-p35. While the majority of these
      proteins mediate their interaction with Cdk5 through p35, implying that p35 may
      act not only as an activator of Cdk5 but also as an adaptor to associate Cdk5
      with its regulators and physiological targets, a small group of other proteins
      are found to link directly with Cdk5. In addition, Cdk5 has been found to
      phosphorylate a diverse list of substrates, further implicating its regulatory
      roles in a wide range of cellular processes. In this review, we present an
      updated inventory of the interacting proteins of Cdk5-p35 kinase and its
      substrates as well as a discussion on the implicated effects of these
      interactions.

PMID- 14673211
TI  - Cdk5 in neuroskeletal dynamics.
AB  - Signal transduction in a broad sense refers to intracellular, molecular changes
      triggered by cues outside the cell in order to bring about behavioral responses
      such as migration, differentiation, secretion, or death. Until recently, the best
      studied end targets of signal transduction pathways were transcriptional
      regulators that contribute to changes in gene expression. However, it is clear
      that many pathways can act through mechanisms other than, or in addition to,
      transcription control. The three major cytoskeletal systems, microtubules,
      intermediate filaments, and filamentous actin, are targets for this kind of
      regulation. Acute changes in cytoskeletal organization are particularly important
      during embryonic development, when many cells are motile and undergo dramatic
      changes in shape. Cytoskeletal dynamics are also important in motile cells in
      adult systems and, in a more limited way, in cells that carry out rapid,
      regulated secretion. Even changes in synaptic efficacy may involve structural
      modifications requiring changes in the neuroskeleton. Cytoskeletal reorganization
      can itself be viewed as signal transduction, producing changes in molecular
      trafficking and interactions. This review considers evidence that cyclin
      dependent kinase 5 is a modulator of neuroskeletal dynamics.

PMID- 14673212
TI  - Cyclin-dependent kinase 5 in neurofilament function and regulation.
AB  - Neurofilaments are neuron-specific intermediate filaments. They are classed into
      three groups according to their molecular masses: neurofilament heavy, middle and
      light chains (NF-H, NF-M and NF-L). Neurofilaments assemble and form through the
      association of their central alpha-helical coiled-coil rod domains. NF-H and NF-M
      are distinct from NF-L as they contain a carboxyl-terminal tail domain, which
      appears to form connections with adjacent structures and other neurofilaments.
      Together with other axonal components such as microtubules, they form the dynamic
      axonal cytoskeleton. They maintain and regulate neuronal cytoskeletal plasticity
      through the regulation of neurite outgrowth, axonal caliber and axonal transport.
      Neurofilaments contain KSP repeats that are consensus motifs for the proline
      directed kinases and are extensively phosphorylated in vivo, and their functions
      are thought to be regulated through their phosphorylation. Cyclin-dependent
      kinase 5 (Cdk5) is a proline-directed kinase, whose activity is restricted to the
      neuron through the neuronal-specific distribution of its activators p35 and p39.
      Cdk5 is the only kinase that affects the electrophoretic mobility of human NF-H
      and is thought to be the major neurofilament kinase. Cdk5 is involved in
      crosstalk with other signal transduction pathways such as the mitogen-activated
      protein kinase and myelin-associated glycoprotein pathways to influence the
      phosphorylation of neurofilaments and other cytoskeletal proteins. Both the
      hyperactivation of Cdk5 activity and subsequent hyperphosphorylation of
      neurofilaments and the microtubule-associated protein tau have been implicated in
      the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and
      amyotrophic lateral sclerosis. Here we review the functions of neurofilaments and
      the significance of Cdk5 phosphorylation of neurofilaments.

PMID- 14673213
TI  - Transcription factor AP-2beta genotype associated with anxiety-related
      personality traits in women. A replication study.
AB  - Attempts to link transmitter system genes to certain aspects of personality have
      been performed. Several monoamine-related gene variants have been investigated.
      We previously reported an association between a transcription factor activating
      protein-2beta (AP-2beta) variant and anxiety-related personality traits as
      estimated by Karolinska Scales of Personality (KSP). To confirm this reported
      association, we have, in the present study, analysed an enlarged group of healthy
      volunteers (n = 370) with regard to AP-2beta genotype and personality traits. For
      estimation of personality traits, individuals completed 5 different personality
      questionnaires, i.e. Swedish Universities Scales of Personality (SSP), Health
      Relevant 5- Factor Personality Inventory (HP5i), Temperament and Character
      Inventory, the Revised NEO Personality Inventory and KSP. In contrast to men,
      women having two long AP-2beta alleles displayed lower scores for muscular
      tension (KSP; F = 10.65, p = 0.0013), somatic trait anxiety (SSP; F = 7.18, p =
      0.0081), trait irritability (SSP; F = 4.51, p = 0.032), mistrust (SSP; F = 4.01,
      p = 0.0468) and negative affectivity (HP5i; F = 10.20, p = 0.0017) than women
      with at least one short allele. The data presented in this study, together with
      our previously published data, suggest that AP-2beta intron 2 genotype is
      associated with low levels of anxiety-related personality traits in women. Hence,
      these data further suggest the human AP-2beta gene as a novel candidate gene in
      personality.

PMID- 14673214
TI  - Relationship between power spectra of the awake EEG and psychomotor activity
      patterns measured by short-term actigraphy.
AB  - Actigraphy is a quantitative method for the measurement of motor activity. In the
      present study, actigraphy was used to examine psychomotor correlates of brain
      activity. Thirty-four psychiatric patients (17 males and 17 females) with
      different diagnoses participated in this investigation. Directly after EEG
      recording, motor activity was measured with a wrist actimeter for 15 min in
      patients in the sitting position. The EEG was quantified by spectrum analysis,
      and the power spectra as well as other EEG-derived variables were correlated with
      actigraphic parameters. Occipital and temporoparietal beta1 power was
      statistically significantly higher in patients with higher activity scores and
      lower in those with a high density of sleep (SB) or wake bouts (WB). A high
      density of SB or WB was also positively correlated with higher mean alpha power.
      Immobile phases measured by actigraphy were positively associated with occipital
      alpha and with frontal/frontopolar delta activity, preferentially on the side of
      the left hemisphere. Our results, while preliminary, suggest that short-term
      actigraphy may be apt to reflect central nervous system arousal.

PMID- 14673215
TI  - Expression of cAMP response element-binding protein in major depression before
      and after antidepressant treatment.
AB  - Antidepressants usually take weeks to exert significant therapeutic effects. This
      lag phase is suggested to be due to neural plasticity, which may be mediated by
      the coupling of receptors to their respective intracellular signal transduction
      pathways. Phosphorylated cAMP response element-binding protein (CREB), a
      downstream target of the cAMP signaling pathway, has been reported to be a
      molecular state marker for the response to antidepressant treatment in patients
      with major depressive disorder (MDD). In order to explore the role of CREB
      expression in MDD, we used quantitative reverse transcriptase-polymerase chain
      reaction to quantify CREB messenger RNA of the peripheral lymphocytes obtained
      from 21 MDD patients, before and after antidepressant treatment, and 21 normal
      controls. The results revealed no significant difference of CREB expression
      between untreated MDD patients and normal controls. However, after 8 weeks of
      antidepressant treatment, CREB expression was significantly decreased in MDD
      patients (p = 0.025). The CREB change is not associated with the types of
      antidepressants and therapeutic response.

PMID- 14673216
TI  - Association study of a brain-derived neurotrophic-factor genetic polymorphism and
      mood disorders, age of onset and suicidal behavior.
AB  - Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin growth
      factor family, has been implicated in both mood disorders and suicidal behavior.
      This study has examined the association between the BDNF gene Val66Met
      polymorphism and mood disorders, age of onset and suicidal behavior in a Chinese
      sample population. The genotype and allele frequencies for the BDNF gene Val66Met
      polymorphism did not differ comparing depression groups (total, bipolar disorder
      or major depression) and control subjects. Furthermore, it was not demonstrated
      that this BDNF polymorphism was associated with age of onset or suicidal history
      in our mood disorder patients. Based on these results, it seems reasonable to
      suggest that this polymorphism is unlikely to play a major role in the genetic
      susceptibility to mood disorders. Given the fact that the positive association
      between BDNF gene Val66Met polymorphism and bipolar disorder has only been
      demonstrated for a Caucasian population but not for a Japanese analog or our
      Chinese sample, it appears likely that this association is ethnicity dependent.

PMID- 14673217
TI  - Association between catechol-O-methyltransferase gene polymorphisms and wearing
      off and dyskinesia in Parkinson's disease.
AB  - Catechol-O-methyltransferase (COMT) is an enzyme that inactivates catecholamines,
      including levodopa. An amino acid change (Val-108-Met) in the COMT protein has
      been found to result in a change from high to low enzyme activity. In the present
      study, we genotyped 121 Japanese patients with Parkinson's disease (PD) and 100
      controls. Comparison of the allele frequencies revealed that homozygosity for the
      low-activity allele was significantly more common among PD patients than the
      controls (p = 0.047, odds ratio = 3.23). In addition, homozygosity for the low
      activity allele was overrepresented in PD patients that exhibited the 'wearing
      off' phenomenon (p = 0.045, odds ratio = 3.82) or dyskinesia (p = 0.030, odds
      ratio = 4.80) compared with controls, although these differences were not
      significant after Bonferroni's correction. Our results may help understand the
      mechanism that cause complications of levodopa therapy in PD patients.

PMID- 14673218
TI  - Confirmation of the neurophysiologically predicted therapeutic effects of
      trazodone on its target symptoms depression, anxiety and insomnia by
      postmarketing clinical studies with a controlled-release formulation in depressed
      outpatients.
AB  - Early human pharmaco-EEG and subsequent sleep laboratory studies identified
      trazodone, a 5-HT(2) antagonist and 5-HT reuptake inhibitor (SARI), as an
      antidepressant with therapeutic effects on its target symptoms depressed mood,
      anxiety and insomnia. On the occasion of the introduction of a controlled-release
      (CR) formulation (Trittico 150 mg retard, marketed in Austria by CSC
      Pharmaceuticals Handels GmbH, Vienna, Austria) in Austria in July 2000, a multi
      center, open, clinical post-marketing study on the therapeutic effects, safety
      and target symptoms of trazodone CR in depression was carried out at 80 offices
      of Austrian neuropsychiatrists. 549 outpatients (63% females) of all age groups
      suffering from five different subtypes of depression were enrolled in the study.
      After a 2-week fixed dose-titration regimen up to 150 mg and a 4-week adjustment
      period to the optimum dose, 66% of the patients remained on 150 mg, 20% increased
      the dose and 11% decreased it. Only 3.7% discontinued treatment. Rating by the
      neuropsychiatrists based on the Clinical Global Impression showed very much to
      much improvement in 78.3% of the patients, and no change or a deterioration in
      only 3.6%. In the Hamilton Depression Scale (HAMD) a statistically significant
      improvement from a baseline score of 21 to a score of 14 after 2 weeks was found,
      and a normalization to a score of 8 after 6 weeks. Therapeutic effects were
      similar in the five groups suffering from different subtypes of depression and in
      patients with and without comedication. Self-rating by the patients based on the
      Zung Self-Rating Depression Scale (SDS) and Zung Self-Rating Anxiety Scale (SAS)
      also showed a significant improvement in the 2nd and 6th week of therapy.
      Evaluation of the target symptoms of trazodone by ranking the most improved
      symptoms identified insomnia as the most improved psychopathological item in all
      three scales. While in the observer ratings also suicidal tendencies and weight
      loss were found much improved, in the self-rated Zung SDS sadness and loss of
      drive came second and third in the improvement ranking, in the self-rated Zung
      SAS anxiety and the feeling of falling apart. Tolerability was very good. In the
      2nd week only 16.9% and in the 6th week only 7.6% of the patients reported side
      effects, mostly characterized by tiredness and rarely by nausea and vertigo. The
      present clinical study is in agreement with previous studies identifying
      trazodone as a safe and effective antidepressant, specifically regarding its
      target symptoms insomnia, depression and anxiety. It also confirms our own early
      predictions based on neurophysiological investigations concerning the mode of
      action of the drug.

PMID- 14673219
TI  - Occurrence of periodic sleep spindles within and across non-REM sleep episodes.
AB  - Sleep spindles have been reported to occur both as single events and periodically
      in sequences. However, there is no systematic description about the occurrence of
      spindles in sequences in relation to time of night. The aim of the present study
      was to examine the temporal occurrence of periodic sleep spindles during the
      night. Sleep spindles of 19 healthy subjects were selected visually. A minimum of
      three consecutive spindles was required to form a spindle sequence. A 5-second
      upper time interval limit was applied as the longest duration between spindles
      belonging to a spindle sequence. The number of spindles and time occupied by
      spindle sequences increased from the first to the fourth non-REM (NREM) sleep
      episode. Within NREM sleep episodes, the number of spindles and spindle sequences
      dominated at the beginning. In the first two NREM sleep episodes with high slow
      wave activity (SWA), there were few spindle sequences and they decreased with
      increasing SWA. In the third and fourth NREM sleep episode with less SWA, there
      were more spindle sequences and they were more evenly distributed. It is possible
      that in the first NREM sleep episodes, hyperpolarization of the thalamocortical
      cells deepens so rapidly that the NREM sleep level, where spindle sequences
      arise, is passed and spindle sequences are not formed. Spindle sequences could be
      regarded as markers of the evolution of the NREM sleep process and their lack or
      excess in relation to time of night and NREM sleep episode can hopefully be used
      to indicate changes in brain mechanisms behind NREM sleep.

PMID- 14673220
TI  - Factors affecting sexual life during pregnancy in eastern Turkey.
AB  - This is a descriptive and cross-sectional study aiming to determine the factors
      affecting sexual life in pregnant women. The study was carried out in 238 women
      in Malatya, Turkey. It was found that 61.4% regarded coitus as a risk during
      pregnancy, 31.9% did not have any knowledge about this matter. In 81.5% sexual
      life was affected during pregnancy. The mean frequency of intercourse was 2.02 +/
      0.7/week before pregnancy and decreased to 1.51 +/- 0.6/week during pregnancy.
      The reasons for this decline are: exhaustion and fatigue (64.3%); waning of
      sexual desire (55.9%); harmful to the fetus (49.2%); causing abortions in early
      pregnancy (45%), and inducing preterm labor (34%). There was a significant
      relationship between changes in sexual life during pregnancy and the duration of
      marriage (chi2=10.8, p<0.05), education level (chi2=18.1, p<0.05), parity
      (chi2=11.1, p<0.05), and gravidity (chi2=6.8, p<0.05). The variables such as age,
      employment status, and number of abortions did not affect sexual life during
      pregnancy.

PMID- 14673221
TI  - [Preterm labour and risk factors].
AB  - Infections, stress and haemorrhages are risk factors in the pathophysiology of
      preterm delivery. Genital infections can be diagnosed and treated, and thus the
      frequency of preterm labour is lowered. How psychosocial burdens which are also
      stress factors can be influenced remains uncertain.

PMID- 14673222
TI  - [Efficient prevention of prematurity - the Thuringian model].
AB  - In two prospective projects, the effectiveness of the self-care programme for
      prematurity prevention developed by Saling was prevented. Pregnant women in
      Erfurt were shown how to perform self-measurements of their vaginal pH by means
      of test gloves twice a week in order to screen for any disturbances in the
      vaginal millieu. The women were instructed to see their physician immediately, if
      abnormal values (ph > or = 4.7) or other risk factors were present, in order to
      start Lactobacillus acidophilus therapy or, in cases of bacterial vaginosis,
      treatment with intravaginal clindamycin cream. Patients who were not interested
      in the programme, served as a control group. 73 out of 381 women in the
      intervention group were identified as risk cases. In this study, the prematurity
      rate was 8.1% in the self-measurement/intervention group versus 12.3% in the
      control group (p < 0.05, n = 2,341); 0.3 versus 3.3% of the neonates belonged to
      the group of very early prematures with a gestational age of <32 + 0 weeks (p <
      0.01). Starting on March 1, 2000, a similar statewide pH screening programme was
      initiated in order to reduce prematurity in the State of Thuringia. According to
      the study design, a significant decrease in prematurity was hypothetically
      expected for the second half of 2000. Data from 16,276 women are available. On
      this basis, a significant reduction of early prematurity from 1.58 to 0.99% was
      seen (p < 0.001). Comparing low birth weights, a significant reduction of cases
      was also achieved in all groups. On the basis of data obtained, we recommend that
      the campaign should be extended to the whole of Germany. This recommendation is
      also supported by the observation that after the campaign had been discontinued
      the prematurity rates monitored in 2002 were as high as they had been prior to
      the introduction of the statewide programme.

PMID- 14673223
TI  - [Gentle obstetrical management for very early preterm deliveries].
AB  - OBJECTIVE: In view of the general improvement in survival of very early preterm
      newborns the contribution of the obstetrical management to this development has
      been studied. METHODS: A comprehensive literature search was performed
      concentrating on prospective randomised clinical trials, meta-analyses and review
      articles dealing with different aspects of the obstetrical management of very
      early preterm deliveries which were published during the last 10 years. RESULTS:
      The benefit of antepartal administration of glucocorticoids to the mother for
      stimulation of pulmonary maturity of the fetus and the overall clinical condition
      of the preterm newborn at birth has been proven by several prospective randomised
      studies. In contrast, there is only indirect evidence for the benefit of an early
      transfer of these pregnancies to a perinatal centre. The benefit of a short-term
      prolongation of pregnancy by the administration of tocolytics is evident in the
      context of glucocorticoid administration for pulmonary maturity. There is no
      clear evidence for the benefit of long-term tocolytic treatment of preterm
      labour. Various prospective randomised trials comparing delivery by primary or
      elective caesarean section with vaginal birth combined with selective section as
      indicated by a deterioration of the condition of the fetus or the mother during
      the first or second stage of labour have clearly shown increased maternal
      morbidity in the elective caesarean section group. The expected advantage for the
      condition of the newborn could not be shown. In a meta-analysis of 6 such trials,
      the problem of recruiting participants was stressed. All 6 trials had to be
      terminated before the calculated number of study participants had been recruited.
      CONCLUSION: For planned early preterm delivery a transfer of the mother into
      perinatal centre is recommended for pregnancies beyond 22 0/7 weeks. Starting at
      24 0/7 weeks, glucocorticoids should be administered. Between 24 0/7 and 24 6/7
      weeks, survival chances remain clearly at less than 50%, and up to 50% of those
      surviving develop moderate to severe handicaps. Obstetrical management, in
      particular a decision for caesarean section due to fetal indication, must be
      individualised taking into account the wishes of the parents. Beyond 25 0/7
      weeks, newborn survival should be given priority, and although clear evidence for
      the optimal mode of delivery is missing in cases of spontaneous labour leading to
      rapid dilatation of the cervix, with a normal singleton cephalic fetus, a vaginal
      delivery may be attempted. If under close supervision of labour there are signs
      of fetal or maternal deterioration, a caesarean section should be performed
      without delay. With breech presentation as well as twins or multiple fetuses
      there is a general trend towards primary caesarean section. In the absence of
      spontaneous labour and with an unripe cervix, elective caesarean section is
      considered as the method of choice for the delivery of the early preterm fetus.

PMID- 14673224
TI  - [Prognosis of preterm infants with a birth weight <1,501 g].
AB  - The prognosis of very low birth weight infants (birth weight <1,501 g) is
      correlated with gestational age. Mortality is between 10 and 16%, showing high
      numbers in infants < or = 26 weeks of gestation. Looking at the low-term outcome,
      cerebral palsy is the most prevalent major disability with an incidence of 8%.
      Similar to mortality, the incidence of cerebral palsy is inversely proportional
      to gestational age. A clinically verified chorioamnionitis increases the risk of
      developing cerebral palsy by a factor of up to 4.

PMID- 14673225
TI  - [Ethical problems regarding extremely preterm infants].
AB  - In the industrialized countries during the last 20 years, ever smaller preterm
      infants have been re-animated after birth, subjected to mechanical ventilation,
      fed parenterally and treated with various drugs. The smaller and more premature
      the infant, the longer the intensive care, the greater pain and suffering for the
      infants concerned and the worse the long-term results. Although mortality
      decreased, chronic problems of the lungs, eyes and brain (cerebral palsy)
      increased in the surviving infants. Therefore specialists as well as the general
      public began to discuss the limits of using intensive medicine. Investigations
      among neonatologists and nursing staff all over Europe resulted in a wide
      spectrum of opinions where the line should be drawn, e.g. concerning gestational
      age. A majority is however in favour of stopping intensive care measures when
      these are not in the best interest of the infant, i.e. when treatment becomes
      painful and inescapable death is only postponed. In order to reach such a
      difficult medico-ethical decision in a structured, understandable and well
      supported way, special procedures were developed, which have stood their test in
      practice.

PMID- 14673226
TI  - [Fluorescence diagnosis with 5-ALA thermogel of cervical intraepithelial
      neoplasia].
AB  - OBJECTIVE: To study the pharmacokinetics and selectivity of 5-aminolevulinic acid
      (5-ALA) from 5-ALA thermolabile gel formulation in cervical intraepithelial
      neoplasia (CIN). The novel thermogel Pluronic F127 is liquid at cold temperatures
      and turns into a gel-like consistency at body temperature, thereby improving
      adhesion of 5-ALA to the cervix uteri. METHODS: 27 female patients with CIN 1-3
      were included in this study. Thirty minutes to 12 h before conisation, 10 mL of
      thermo-gel containing either 4, 10, or 20% of 5-ALA were topically applied to the
      cervix. Biopsies were taken from the lesions as well as normal surrounding
      epithelial tissue for histological examination, fluorescence microscopy and
      spectrometry. RESULTS: The thermogel Pluronic F127 was easy to handle and proved
      reliable as vehicle carrier. 5-ALA induced porphyrin fluorescence was maximal
      after application of 10% 5-ALA thermogel. We observed the higher porphyrin
      fluorescence intensity within the CIN lesions (1,116 +/- 241 AU), as compared to
      normal adjacent epithelium (704 +/- 166 AU). This difference was statistically
      significant (p < 0.05). Four to six hours after application, porphyrin
      fluorescence in dysplastic epithelium reached maximal intensity, and tumor
      selectivity was the highest in CIN 3 achieving a tumor-to-normal ratio of 3.5.
      Compared to other studies employing 5-ALA, the thermogel preparation of 5-ALA
      leads to twofold increase in the porphyrin selectivity. CONCLUSIONS: The
      thermogel Pluronic F127 seems to improve the local cervical drug application.
      Based on these results, we recommend the application of a 10% 5-ALA thermogel
      formulation 4-6 h prior to photodynamic therapy in CIN.

PMID- 14673228
TI  - Association between IL-1ra gene polymorphism and premature delivery.
AB  - IL-1 receptor antagonist (IL-1ra) gene polymorphism was examined in 95 Israeli
      preterm newborns and compared to that of adult volunteers. The genotype was
      determined using PCR amplification of the variable region of intron 2 of the IL
      1ra gene. The IL-1raA1 allele was found to be predominant in the two groups.
      However, a significant higher frequency of IL-1raA2 allele was found in preterm
      newborns. The difference was mainly due to higher proportion of homozygous for IL
      1raA2 in the preterm neonates (19%) as compared with adults (7%). No such
      association could be demonstrated between IL-1raA2 allele and severe sepsis in
      preterm newborns. The frequency of IL-1raA2 allele among preterms with a septic
      episode did not differ significantly from that found in newborns without sepsis.
      The results suggest an association between the IL-1ra genotype and the incidence
      of premature delivery.

PMID- 14673229
TI  - Welcome to SKINmed.

PMID- 14673230
TI  - O case report, where art thou?

PMID- 14673231
TI  - Teledermoscopy: a specific application of teledermotology.

PMID- 14673232
TI  - Jumping into the future using teledermoscopy.
AB  - BACKGROUND: Teledermoscopy uses telecommunication technologies to transfer images
      of pigmented skin lesions via the Internet for teleconsultation. DESIGN: Clinical
      and dermoscopic images of 66 and 43 pigmented skin lesions achieved in two
      consecutive studies were sent by e-mail to dermatologists with different degrees
      of experience in dermoscopy for a telediagnosis. All lesions included in these
      studies were surgically excised and diagnosed histopathologically. RESULTS: The
      diagnostic concordance between the face-to-face diagnosis and the telediagnosis
      was 91% in the first study, whereas, in the second study, it varied from 76.7%
      95.3%. The accuracy of the diagnoses in both studies was not related to the
      quality of the images, but did highly depend on the level of diagnostic
      difficulty of a given pigmented skin tumor and on the level of experience of each
      observer. CONCLUSIONS: Teleconsultation of dermoscopic images of pigmented skin
      lesions via e-mail provides a similar degree of diagnostic accuracy as face-to
      face diagnosis when the diagnosis is made by a dermatologist confident with
      dermoscopy.

PMID- 14673233
TI  - Gender differences in vesiculobullous autoimmune skin diseases.
AB  - Autoimmune vesiculobullous skin diseases are a common occurrence in dermatology
      practice and do have gender differences. While most dermal antigens and
      autoantibodies in these diseases have been identified, the etiology and clinical
      characteristics of the autoimmunity remain obscure, such as why more than 70% of
      autoimmune diseases are more frequent in women. Researching gender differences
      and the mechanisms of autoimmune diseases will shed light on the answers to such
      questions.

PMID- 14673234
TI  - Cutaneous reactions to antibacterial agents.
AB  - Antibacterial agents may cause a variety of untoward reactions. Some range from
      transient, mild erythema to toxic epidermal necrolysis, often resulting in
      disability and death. Both in vivo and in vitro tests are becoming useful for the
      diagnosis of the causative agent in drug eruptions. The drug hypersensitivity
      syndrome may be associated with thyroid abnormalities often occurring months
      after the drug has been withdrawn. Symmetrical small joint polyarthritis, fever,
      and malaise may be the presenting findings in a patient with drug-induced lupus
      erythematosus. Exanthematous drug eruptions without high fever, mucosal
      involvement, or joint symptoms often resolve without discontinuation of the drug.
      The differential diagnosis of Stevens-Johnson syndrome and toxic epidermal
      necrolysis depends on the percentage of epidermal detachment.

PMID- 14673235
TI  - Criteria for establishing occupational causation--"hit or miss" conception?

PMID- 14673236
TI  - Some considerations on hemangioma.

PMID- 14673237
TI  - Sexually transmitted diseases are alive and well.

PMID- 14673238
TI  - Lichen planus.

PMID- 14673239
TI  - Persistent herpes gestationis.

PMID- 14673240
TI  - Periostomy dermatitis: a novel therapeutic approach.

PMID- 14673241
TI  - Nocardia otitidiscaviarum: an unusual Nocardia species causing a primary
      lymphocutaneous infectious process in a mildly immunosuppressed patient.

PMID- 14673243
TI  - Cutaneous signs update.

PMID- 14673244
TI  - The tongue speaks in many ways.

PMID- 14673245
TI  - Oral lichen planus part I: epidemiology, clinics, etiology, immunopathogeny, and
      diagnosis.
AB  - This article presents a review of the literature on oral lichen planus, focusing
      on important aspects of its epidemiology, etiopathogeny, and clinical
      manifestations. The oral form is an important clinical presentation of lichen
      planus. It may precede or accompany the skin lesions, or it may be the only
      manifestation of the disease. Dermatologists, dentists, otorhinolaryngologists,
      and other specialists who deal with the oral cavity must be aware of this disease
      so they can diagnose, treat, and keep these patients under observation.

PMID- 14673246
TI  - Erectile dysfunctions.
AB  - Erectile dysfunction is one of the prime challenges confronting the treating
      physician. Its prevalence is directly proportional to aging. It is imperative to
      comprehend the intricate mechanism of erection in order to individualize the
      approach to management. Thus, it is appropriate to evaluate the etiology of
      erectile dysfunction. Normal aging, as well as psychogenic, vascular, neurogenic,
      and endocrinologic causes and/or those due to structural abnormalities of the
      penis should be considered when evaluating details to determine its probable
      cause. An increasing use of drugs, a legacy of civilization, has considerably
      compounded the problem. Therapy for erectile dysfunction, apart from psychosexual
      counseling, includes medical treatment by alpha adrenoceptor antagonists,
      dopamine agonists, phosphodiesterase type 5 inhibitors, sublingual apomorphine
      hydrochloride, or hormone therapy. Transdermal or transurethral corporeal drug
      delivery are other possible treatment modalities. Vacuum devices and surgical
      approaches are considered relevant only in refractory cases.

PMID- 14673247
TI  - Latex allergy.
AB  - Allergy to natural rubber latex affects people routinely exposed to rubber
      products. Groups thought to be at highest risk include atopics, health care
      workers, rubber industry workers, and individuals who have undergone multiple
      surgical procedures, especially those with spina bifida. Allergy to latex is a
      type I, immediate, IgE-mediated reaction that can lead to anaphylaxis and death.
      The prevalence, risk factors, clinical manifestations, diagnosis, and management
      of latex allergy are summarized in this review.

PMID- 14673249
TI  - ADOXA (doxycycline).

PMID- 14673250
TI  - Sensitive skin products: 2003.

PMID- 14673251
TI  - Delusions of parasitiosis: a case with a review of its course and treatment.

PMID- 14673252
TI  - Herman V. Allington, A. Fletcher Hall, and the introduction of liquid nitrogen.

PMID- 14673253
TI  - Should a patient with a history of melanoma be advised against the use of oral
      contraceptives? The relatives are worried.

PMID- 14673254
TI  - Mucous aggregate of the nasopharynx: the mucolith.

PMID- 14673255
TI  - Fibroepithelioma of Pinkus presenting as a sessile thigh nodule.

PMID- 14673256
TI  - Netherton syndrome.

PMID- 14673257
TI  - Disseminated superficial actinic porokeratosis in a patient with Sjogren
      syndrome.

PMID- 14673258
TI  - Cosmetic dermatology and Art Deco: lookin' good.

PMID- 14673259
TI  - Imiquimod and the treatment of cutaneous T-cell proliferative diseases: at the
      threshold.

PMID- 14673260
TI  - Polyarteritis nodosa and cutaneous polyarteritis nodosa.
AB  - Cutaneous vasculitis can present with a variety of lesions and associated
      symptoms. It is important for the clinician to be able to recognize vasculitis
      lesions and know when to pursue further laboratory studies that will determine
      the extent of the disease process in a patient. This review compares and
      contrasts polyarteritis nodosa with its cutaneous counterpart. The diagnostic
      workup and management of these two entities as well as the overall approach to a
      patient with a possible vasculitic condition are emphasized.

PMID- 14673261
TI  - Evolution of biologic therapies for the treatment of psoriasis.
AB  - Over the past three decades, laboratory and clinical research findings have shown
      that T cells are the primary mediators of psoriasis pathogenesis and that
      psoriasis can be treated by eliminating these T cells or interfering with their
      activation or activity. Based on these observations, many new biologic therapies
      to treat psoriasis are now in development. These agents, developed primarily
      through recombinant DNA techniques, are designed to target T cells and the
      immunologic cascade associated with their activation. Four basic strategic
      approaches that focus on the steps involved in the immunopathology of psoriasis
      are: 1) elimination of the pathogenic T cells; 2) inhibition of T-cell
      activation, proliferation, and migration; 3) immune deviation to down-regulate
      the type 1 (TH1) response predominant in psoriasis; and 4) blockade of cytokine
      production. The goal of these new therapies is to improve the treatment of
      psoriasis, particularly moderate to severe disease, with agents that are well
      tolerated and safe for long-term use.

PMID- 14673262
TI  - Chemical warfare agents: their past and continuing threat and evolving therapies.
      Part II of II.
AB  - Chemical warfare agents are ideal weapons for terrorists and for use in military
      operations against both civilian populations and troops. Thus, there have been
      efforts by the United States in cooperation with other concerned nations to
      develop animal models to understand the pathophysiology of the injuries induced
      by these agents, and to develop suitable animal models for testing of pre-and
      post-exposure protectants and therapies. Sulfur mustard remains the most
      significant chemical warfare agent that produces cutaneous injuries. Institution
      of standard recommendations prior to threatened exposure or after exposure are
      something that we need to be aware of in the world we live in. In addition, pre
      and post-exposure therapies now being studied offer hope for moderating the
      mortality and morbidity that can result from chemical exposure.

PMID- 14673263
TI  - The introduction of topical corticosteroids.

PMID- 14673264
TI  - A novel use of topical anesthetics to alleviate the pain of cryotherapy.

PMID- 14673265
TI  - Acne vulgaris.

PMID- 14673266
TI  - Cutaneous lymphomas and association to sex hormones.
AB  - Male gender is interpreted as a risk factor for developing mycosis fungoides and
      perhaps other cutaneous and extracutaneous lymphomas. In this review the authors
      examine epidemiologic, clinical, pathologic, and molecular data in an effort to
      understand whether and to what extent gender or sex hormones are involved in the
      pathogenesis of lymphoproliferative disorders.

PMID- 14673267
TI  - Topical imiquimod therapy for cutaneous T-cell lymphoma.

PMID- 14673268
TI  - Familial epidermolysis bullosa with aplasia cutis congenita: Bart's syndrome?

PMID- 14673269
TI  - Multiple syringomas in an unusual distribution.

PMID- 14673270
TI  - Antimicrobials in the treatment of acne and rosacea.

PMID- 14673271
TI  - Risks and precautions of chemical warfare agents.

PMID- 14673272
TI  - Medication adherence for acne vulgaris.

PMID- 14673273
TI  - Botulinum toxin in the treatment of axillary hyperhidrosis.
AB  - INTRODUCTION: Axillary hyperhidrosis can be a source of social isolation and
      embarrassment. The available treatments are either ineffective or have
      intolerable side effects. The search for a simple, long-lasting, and safe
      treatment has led to the use of botulinum-A toxin injections in those with
      excessive axillary hyperhidrosis. MATERIALS AND METHODS: Fifteen patients
      participated in this study. All had a history of axillary hyperhidrosis of 1-6
      years duration and were using different types of therapies without any benefit.
      Each patient was injected intradermally with 125 units of botulinum-A toxin
      (Dysport, Spenywood Pharmaceutical) in 5-6 points over an elliptical area on each
      side. Patient follow-up was performed using the iodine-starch test. RESULTS: A
      total of 14 out of the 15 patients had complete anhidrosis 1 week after the
      injection. This result lasted for periods ranging from 1-6 months. No side
      effects were encountered. CONCLUSION: Intradermal injection of botulinum-A toxin
      seems to be a safe, rapid, and effective method of treatment in axillary
      hyperhidrosis.

PMID- 14673274
TI  - Chemical warfare agents: their past and continuing threat and evolving therapies.
      Part I of II.
AB  - Chemical warfare agents are potentially accessible to even underdeveloped nations
      because they are easily and inexpensively produced. This means that they are
      ideal for use by terrorists and in military operations against civilian
      populations and troops. In terms of cutaneous injury, vesicants-mainly sulfur
      mustard-are the most significant chemical warfare agents. Advances in
      understanding the pathophysiology of the lesions produced by sulfur mustard have
      led to the research and development of barrier creams as well as pre- and post
      exposure therapies to moderate the damage and accelerate healing. Part I of this
      paper will discuss the history and classification of chemical agents; Part II,
      which will appear in the September/October 2003 issue of SKINmed, will discuss
      characteristic manifestations of exposure to chemical agents, as well as
      prevention and therapy.

PMID- 14673275
TI  - Assessment of etiologic agents in acne pathogenesis.
AB  - Acne is a chronic inflammatory disease of the pilosebaceous units. Traditional
      etiologic factors include increased sebum production, ductal hyperkeratosis,
      abnormality of the microbial flora within the pilosebaceous unit, and mediators
      of inflammation. Recent developments do not refute these familial elements, but
      rather refine particular aspects. Interleukin-1a influences hypercornification of
      the infundibulum as well as the inflammatory response by inducing the production
      of vascular endothelial growth factor in dermal papilla cells and follicular
      keratinocytes of the pilosebaceous unit. New retinoids have been developed based
      on controlling cellular proliferation and differentiation in the pilosebaceous
      unit by their action on nuclear receptors of cells. Dermal inflammation is not
      due to presence of bacteria, but from biologically active mediators produced by
      Propionibacterium acnes. The environment within the pilosebaceous unit is
      probably more important than the absolute number of P. acnes organisms. Indeed,
      the major role of the sebaceous gland appears to be supplying P. acnes needed
      nutrients. Moreover, the microbiologic principle of biofilms appears to be
      applicable to P. acnes in acne.

PMID- 14673276
TI  - How do you foster medication adherence for better acne vulgaris management?
AB  - Suboptimal medication adherence is one of the major reasons for treatment failure
      among patients with acne vulgaris. Motivating patients to adhere to treatment,
      especially during the maintenance phase, remains a challenge. Although the
      literature on medication adherence in the acne vulgaris patient population is
      sparse, the available literature on patients with dermatologic and
      nondermatologic disorders suggests that a multifactorial approach, combining
      nonpharmacologic interventions and effective, well tolerated, and simplified drug
      regimens, appears to be associated with the greatest success. Furthermore, it is
      important to evaluate the patient for underlying affective disorders (e.g.,
      depression) that can undermine adherence. The dermatologist can play a major role
      in enhancing patient adherence by prescribing adherence-enhancing therapeutic
      regimens and by forming a therapeutic alliance with patients.

PMID- 14673277
TI  - Subantimicrobial dose doxycycline for acne and rosacea.
AB  - Acne vulgaris and rosacea present therapeutic challenges due to their chronicity,
      potential for disfigurement, and psychosocial impact. Although
      pathophysiologically distinct, both conditions have major inflammatory
      components. Consequently, topical and systemic antimicrobial agents are routinely
      prescribed for extended periods. Emergence of resistant strains of
      Propionibacterium acnes, adverse events, and compliance issues associated with
      chronic systemic tetracycline use have led to new treatment approaches. At
      subantimicrobial doses, tetracyclines reduce inflammation via anticollagenolytic,
      antimatrix-degrading metalloproteinase, and cytokine down-regulating properties.
      Subantimicrobial dose (SD) doxycycline (Periostat 20 mg) has clinical utility in
      periodontitis and has been investigated in a double-blind, placebo-controlled
      trial in the treatment of moderate facial acne as well as in an open label study
      in the treatment of rosacea. The results of subantimicrobial dose doxycycline
      treatment in early trials support its benefits and further investigation in acne
      and rosacea.

PMID- 14673278
TI  - Intractable cellulitis and a solitary pulmonary nodule.

PMID- 14673279
TI  - The skin biopsy and cutaneous medicine: why biopsy the obvious?

PMID- 14673280
TI  - Recurrent squamous cell carcinoma in situ of the finger.

PMID- 14673281
TI  - Herpes zoster: reassessment of isolation-precautions in hospitals.

PMID- 14673282
TI  - Dubai Derma 2003: Dubai World Dermatology and Laser Conference and Exhibition.
      May 11-13, 2003, Dubai, United Arab Emirates.

PMID- 14673283
TI  - Subcorneal pustular dermatosis developing in a patient with rheumatoid arthritis;
      rheumatoid, antimicrosomal, and antimitochondrial autoantibodies; and a goiter.

PMID- 14673284
TI  - Persistent erythema, telangiectases, and facial flushing after carcinoid tumor
      excision.

PMID- 14673285
TI  - Henoch-Schonlein purpura in an adult.

PMID- 14673286
TI  - Editing a dermatology journal and the Council of Dermatology Editors.

PMID- 14673287
TI  - The annual International Day of Dermatology: a proposal.

PMID- 14673288
TI  - An appraisal of terms used in dermatology.

PMID- 14673289
TI  - Alternative or complementary medicine: opportunities for integration.

PMID- 14673290
TI  - New uses of vinyl tape for reliable collection and diagnosis of common
      superficial mycoses.
AB  - BACKGROUND: Scalpel blade sampling of a lesion with clinical suspicion of
      superficial mycosis may eventually harm the patient, especially anxious children,
      and when sampled from areas such as the neck and the genitals. In these cases-
      provided that an acceptable level of confidence in results can be warranted-
      vinyl tape skin strippings, or strip cultures, could be preferable. PATIENTS AND
      METHODS: Eighty-five patients presenting with scaly lesions clinically suspected
      of superficial mycoses were randomly included in this study. Thin, crystal clear
      vinyl tape strips were firmly applied to lesions, pulled up, and then attached
      glue-face down to glass slides, on which a drop of 10% potassium hydroxide/40%
      dimethyl sulfoxide solution had previously been placed. Once scales were cleared,
      microscopic examination was performed. For specimens yielding negative results,
      further scales were scraped from lesions, cleared, and examined in the
      conventional manner. Patients with proven negative results in both techniques
      have been considered a control group. RESULTS: Sixty cases of superficial mycoses
      were confirmed (dermatophytosis, 38; candidiasis, 12; tinea versicolor, 10). Of
      these, 59 (98.33%) yielded positive results on vinyl tape preparations, with
      clear visualization of organisms' structures. The technique failed to demonstrate
      fungal elements in a single case, subsequently diagnosed as tinea capitis. The
      additional 25 patients were regarded as our control group. CONCLUSIONS: In
      addition to improved patient compliance, ease of performance, and low cost, the
      technique seems appropriate for using in an office environment during a routine
      medical visit. Whenever vinyl tape specimens yield negative results, a scraping
      sampled preparation should be provided.

PMID- 14673291
TI  - Evaluating patient acceptance of a teledermatology link of an urban urgent-care
      dermatology clinic run by residents with board certified dermatologists.
AB  - BACKGROUND: A teledermatology system was established in a dermatology urgent-care
      clinic staffed by dermatology residents in the emergency department. These
      residents had previously lacked attending dermatology supervision. METHODS AND
      PATIENTS: Resident physicians took digital pictures of patients' lesions and
      downloaded the images onto a network personal computer (PC). The images were
      stored on the hospital's server and then viewed within 5 minutes by an attending
      dermatologist, in a different location, using a network PC with monitor. Resident
      and attending physicians discussed the cases over the telephone. Patient
      acceptance was assessed via separate written surveys. Fifty-one patients,
      approximately 10 resident physicians, and two attending dermatologists
      participated in the study. RESULTS: Patient acceptance of the teledermatology
      system was high (93%). Teledermatology may prove a viable means of evaluating
      dermatologic complaints in the emergency department.

PMID- 14673292
TI  - PEMPHIGUS: an acronym for a disease with multiple etiologies.
AB  - The acronym PEMPHIGUS is suggested to encompass the numerous factors involved in
      the pathogenesis and course of the disease. In the following review the authors
      present studies documenting these factors. The acronym can serve as a handy tool
      to direct the physician's investigation of a case of pemphigus, aiding in its
      diagnosis and in the prevention of future flare-ups.

PMID- 14673294
TI  - Medical and cutaneous disorders associated with homelessness.
AB  - Homelessness is a rising problem with socioeconomic roots that affects millions
      of people around the world. Homeless people suffer from a wide range of health
      problems and, consequently, have high rates of morbidity and mortality. Various
      infectious and noninfectious skin conditions have been described among the
      homeless, with trauma, superficial fungal infections, and foot problems being the
      most prevalent. Poor hygiene conditions, exposure to harmful environmental
      agents, and impaired access to health care may further exacerbate these skin
      diseases and lead to serious and occasionally life-threatening situations. As an
      integral part of the medical care for the homeless, dermatologic care is
      essential in diagnosing and managing their skin diseases, in preventing more
      serious complications and in improving the overall health status of the homeless
      population.

PMID- 14673295
TI  - Dermatologic manifestations of complementary therapy.
AB  - The dermatologic manifestations of complementary therapy include reactions to
      herbs used orally and topically for treating skin disease, cutaneous reactions to
      drugs used orally and topically for treating other diseases, and reactions to
      alternative interventions. The safety of alternative medicine is in question.
      Unlike approved drugs, the quality, efficacy, and safety of herbal medicines is
      not regulated. Herbal medicines may be misidentified and contaminated with a
      variety of substances. The following review identifies and categorizes therapies
      according to their common uses with their adverse reactions.

PMID- 14673296
TI  - Breaking the rules of topical skin therapeutics.

PMID- 14673297
TI  - Malignant melanoma: it pays to be a woman.

PMID- 14673298
TI  - Update on gonorrhea.

PMID- 14673299
TI  - Fusarium solani infection complicated by tuberculous omarthritis.

PMID- 14673300
TI  - Hibernoma in the left scapula.

PMID- 14673301
TI  - Subungual melanoma in situ in an 18-year-old patient.

PMID- 14673302
TI  - Cutaneous morphology: the basic tool of dermatology.

PMID- 14673303
TI  - Preserving the art of observation.

PMID- 14673304
TI  - Laser surgery in dark skin.
AB  - Although challenging, effective laser surgery in patients with darker skin tones
      can be achieved despite a higher inherent risk of untoward side effects. While
      the incidence of undesirable postoperative sequelae has decreased with the
      development of advanced laser technology and individualized treatment parameters,
      these risks may never be eliminated completely. Consequently, thorough patient
      preoperative preparation and education regarding the risks of cutaneous laser
      therapy will remain an essential component of treatment in darkly pigmented
      patients. In the future, as more refined laser techniques evolve, the ability to
      safely and effectively treat these patients will improve.

PMID- 14673306
TI  - Nevus of Ota: clinical aspects and management.
AB  - Nevus of Ota, or nevus fuscoceruleus ophthalmomaxillaris, is a dermal melanocytic
      hamartoma that presents as bluish hyperpigmentation along the first or second
      branches of the trigeminal nerve. Extra-cutaneous involvement has been reported,
      especially ocular involvement. Nevus of Ota affects between 0.014%-0.034% of the
      Asian population. Clinical differential diagnoses include facial cafe-au-lait
      patch, spilus nevus, and acquired bilateral nevus of Ota-like macules. Previous
      treatment modalities, including cryotherapy and microsurgery, can be associated
      with scarring. In the last decade, the use of Q-switched lasers has
      revolutionized the treatment of this condition. This review summarizes the
      clinical, histologic, and management aspects of this dermal melanocytic
      hamartoma.

PMID- 14673307
TI  - The farmer and the tractor.

PMID- 14673308
TI  - Cutaneous signs.
AB  - Cutaneous signs play a significant role in clinical medicine. Signs have often
      been named after the initial observer. They may indicate either dermatologic or
      systemic illness and aid the examiner in diagnosis and relevant investigations.
      Some are specific, some have been described in other conditions, and few have
      lost their relevance. Most of the signs are related to the pathogenesis of the
      disease but the cause of some is not clear.

PMID- 14673309
TI  - Genital herpes infection: beyond a clinical diagnosis.

PMID- 14673311
TI  - Gender differences in collagen diseases.

PMID- 14673312
TI  - Atopic dermatitis.

PMID- 14673313
TI  - Dermatofibrosarcoma protuberans: surgical treatment options.

PMID- 14673314
TI  - Topical 5-fluorouracil.

PMID- 14673315
TI  - Warfarin-induced skin necrosis.

PMID- 14673316
TI  - Cutaneous (papulo-nodular) sarcoidosis following hilar lymphadenopathy: an
      intriguing manifestation.

PMID- 14673317
TI  - Severe erythrodermic atopic dermatitis treated with montelukast.

PMID- 14673318
TI  - Monday morning quarterbacking: the dermatologic consultation.

PMID- 14673319
TI  - Dysplastic nevus declassified: even the NIH recommends elimination of confusing
      terminology.

PMID- 14673320
TI  - A comparison of the concordance of digital images, live examinations, and skin
      biopsies for the diagnosis of hospitalized dermatology consultation patients.
AB  - OBJECTIVE: The goal of this study was to compare live and digital image
      examination of hospitalized dermatology consultation patients. DESIGN: A medical
      student digitally imaged patients with a Nikon Coolpix 950 digital camera (Nikon
      Corp., Tokyo, Japan). A resident reviewed these images and the student recorded
      the differential diagnosis. Digital examination was followed by live dermatologic
      examination by the dermatology resident and then by a supervising board certified
      dermatologist. The diagnoses in 29 of these cases were compared with definitive
      diagnostic tests (e.g., skin biopsy). SETTING: Montefiore Hospital, Bronx, NY
      Patients. In March, 2000, 48 of 58 consecutive hospitalized patients for whom
      dermatology consultations were requested and from whom consent for photographs
      could be obtained. MAIN OUTCOME MEASURES: The accuracy and consistency of the
      examiners top (up to three) digital diagnoses, (up to three) live diagnoses, and
      histopathologic diagnoses were compared. RESULTS: Eighty-one percent (38/47) of
      resident digital consult diagnoses agreed with live resident diagnoses. Live
      resident diagnosis agreement with live supervising board certified dermatologists
      diagnosis was 90% (18/20). Resident digital image diagnosis correlation with
      definitive diagnostic test results was 76% (22/29). Live supervising board
      certified dermatologist diagnosis correlation with definitive diagnostic test
      results was 73% (14/19). CONCLUSIONS: Digital image review results in reliable
      and accurate diagnosis compared to live consultations. For inpatient
      consultations, three-dimensional lesions are more amenable to digital diagnosis
      than flat, generalized rashes.

PMID- 14673321
TI  - Diagnosis and treatment of cutaneous melanoma: a practical guide.
AB  - During the past decades, a number of new scientific evidences have been provided
      allowing a better understanding of the nature of cutaneous melanoma. New
      scientific methods, such as dermoscopy, have been shown to improve the diagnostic
      accuracy of pigmented skin lesions and early recognition of melanoma. Aggressive
      approaches for the surgical treatment of melanoma have been shown to be useless
      and have been replaced by more conservative surgical protocols and by sentinel
      lymph node biopsy. In the advanced stage of melanoma, new chemotherapy protocols
      and immunotherapy have been proposed, whereas the role of vaccines is still under
      investigation. In this review, the authors present an up-to-date overview of the
      epidemiologic, clinical, histopathologic, and therapeutic aspects of melanoma
      that can be used as a practical guide for the management of this tumor.

PMID- 14673322
TI  - Cutaneous manifestations of disease in athletes.
AB  - Various means of skin injury in athletes are examined, supplementing those
      discussed in Cutaneous Manifestations of Disease Part 1 (November/ December).
      Skin injury due to mechanical means such as corns, calluses, talon noir
      (calcaneal petechiae), tennis toe, joggers nipples, and piezogenic pedal papules
      will be discussed followed by a thorough discussion of environmental means of
      skin injury. There are a variety of ways that the environment may affect athletes
      both during competition and years after the competition is finished. The
      discussion will conclude with a look at performance-enhancing drugs and their
      effect on an athletes skin, and how the practitioner can better appreciate and
      perhaps prevent the long-term sequelae of drug abuse.

PMID- 14673323
TI  - The proposed inflammatory pathophysiology of rosacea: implications for treatment.
AB  - The pathophysiology of the vascular and inflammatory stages of facial rosacea and
      proposes an underlying cause is reviewed. It can be argued that all the stigmata
      of rosacea are manifestations of an inflammatory process: neutrophilic
      dermatosis. For this reason, treatments that block neutrophil involvement in the
      development of rosacea, such as topical metronidazole and systemic antibodies,
      should be considered first-line therapy for all stages of the disease.

PMID- 14673324
TI  - Corticosteroids are contraindicated in acne patients.

PMID- 14673325
TI  - Always consider syphilis.

PMID- 14673326
TI  - New frontiers in medical photography: teaching and patient care.

PMID- 14673328
TI  - First branchial cleft sinus.

PMID- 14673329
TI  - Prescleroderma: a distinct stage of systemic sclerosis.

PMID- 14673330
TI  - Circinate sarcoidosis of the face.

PMID- 14673331
TI  - Namely a name: atopic dermatitis, decubitus ulcers, scabies...

PMID- 14673332
TI  - Infection, skin disease, and developing countries.

PMID- 14673333
TI  - School rash syndrome: the experience in northwest Ohio.

PMID- 14673334
TI  - Multiple glomus tumors: recognition and diagnosis.
AB  - BACKGROUND: Glomus tumor is a benign neoplasm of uncommon occurrence in daily
      practice, more frequently observed as a single painful lesion, at the distal
      phalanges of the fingers. Multiple presentation is very rare, with fewer than 200
      reports, usually presenting as small angiomatous lesions with discrete pain.
      OBJECTIVES: The study's objective was to analyze the epidemiologic, clinical,
      therapeutic, and histopathologic aspects in a series of six cases of multiple
      glomus tumors. RESULTS: All patients were men, between 12-45 years of age. The
      tumor was congenital or appeared between 3-25 years of age. The clinical picture
      oscillated between three to 10 lesions, as macules, nodules, or tumors, with
      colors varying from bluish, brown-bluish, violet, to normochromic. The lesions
      were detected in the trunk and one or more members, not affecting the head,
      hands, and feet. Pain was discrete or absent. Incisional biopsy for
      histopathologic evaluation with the hematoxylin-eosin staining confirmed the
      diagnosis of glomus tumor in all cases. It showed the characteristic glomus cells
      and vascular spaces. The complete excision of the tumorous plaque was performed
      in one patient and a complex corrective procedure is still to be performed for
      one aberrant tumor in another case. The other patients received advice about
      their disease and were asked to periodically return. CONCLUSION: Because this is
      a very uncommon illness, the present series allowed the demonstration of the wide
      variety of epidemiologic and clinical aspects described in the literature, with
      the presentation of elements that may improve its recognition and diagnosis.

PMID- 14673335
TI  - Patterns of chronic dermatoses in an Ethiopian central teaching hospital: a
      histopathologic approach.
AB  - BACKGROUND: This study was designed to describe the causes and distributional
      patterns of chronic infective-parasitic dermatoses. METHODS: A histology-based
      cross-sectional study was conducted for the years between January 1985 and
      December 1998 within the Tikur Anbessa Hospital, Department of Pathology, Addis
      Ababa University. The data were retrieved from the department's archives and all
      dermatologic cases fulfilling bacterial, viral, fungal, and parasitic etiologies
      were included in the study. Formalin fixed, and paraffin embedded tissues were
      stained with the routine hematoxylin and eosin staining procedure and visualized
      under light microscopy. RESULTS: Out of 162 cases of chronic specific infective
      parasitic dermatoses diagnosed, the mean ages for men and women were 31.5 (SD,
      16.6) and 25.1 (SD, 14.3) years respectively and the peak age group was 20-29
      years (30.2%). Moreover, the ratio of men to women was 1.1:1. The most commonly
      diagnosed dermatosis was wart (38.9%), followed by cutaneous tuberculosis
      (17.9%), and cutaneous leishmaniasis (14.2%). The most frequently involved region
      was the lower limb (46.3%), followed by the face (23.5%). CONCLUSION: This study
      tried to surface the frequency distribution of the histopathologically-proven
      dermatoses that are prevalent in our part of the world. The lower limbs being the
      most frequent sites of dermatoses, their predisposing factors need to be
      addressed in our communities in order to lessen the effects of these dermatoses.
      This study may act as a baseline for similar investigations that may be
      undertaken in the future.

PMID- 14673336
TI  - Cutaneous manifestations of disease in athletes.
AB  - In this first part of a two part series, we will discuss infectious means of skin
      injury and contact sensation in regard to athletic participation. Part 2 will
      address mechanical means and environmental means of skin injury as well as
      performance enhancing drugs used in sports and their effects on the skin.

PMID- 14673337
TI  - Hydroxycarboxylic acids, N-acetylamino sugars, and N-acetylamino acids.
AB  - Most alpha-hydroxyacids and polyhydroxy acids are physiologic, natural, and
      nontoxic substances. All members of the group promote normal keratinization and
      desquamation. Those with multiple hydroxyl groups are moisturizing antioxidants,
      and are especially gentle for sensitive skin. Alpha-hydroxyacids and polyhydroxy
      acids can increase biosynthesis of glycosaminoglycans and collagen fibers, and
      cause substantial skin plumping and increased dermal thickness. Formulation of
      alpha-hydroxyacids and polyhydroxy acids in combination with pharmaceutical
      agents can enhance efficacy and diminish or eliminate side effects and drug
      resistance. N-acetylamino sugars and N-acetylamino acids are two other categories
      of physiologic substances that can: 1) increase skin thickness; 2) improve
      wrinkles and photoaged skin; and 3) eradicate itch in senile and eczematous
      dermatitis.

PMID- 14673338
TI  - A cause for frowning: the BOTOX party.

PMID- 14673339
TI  - Psoriasis.

PMID- 14673340
TI  - A historical perspective of local anesthesia.

PMID- 14673341
TI  - Through the looking glass--what's ahead in clinical research.

PMID- 14673342
TI  - Lentigo maligna of the cheek: discussion of surgical treatment options.

PMID- 14673343
TI  - Is eosinophilia helpful in diagnosing drug eruptions?

PMID- 14673344
TI  - Annual Congress of the Dermatological Society of South Africa, Durban
      International Convention Centre, April 17-20, 2002.

PMID- 14673345
TI  - Tanapox virus infection.

PMID- 14673346
TI  - Generalized diffuse melanosis evolved from erythroderma with hypereosinophilia
      and hyper-IgE.

PMID- 14673347
TI  - Familial pityriasis rubra pilaris (adult classic-I): a report of three cases in a
      single family.

PMID- 14673361
TI  - The future of the cervical spine: Presidential address to the Cervical Spine
      Research Society.

PMID- 14673362
TI  - Load sharing in Premier and Zephir anterior cervical plates.
AB  - STUDY DESIGN: An in vitro biomechanical study using a simulated anterior cervical
      discectomy and interbody fusion model to compare the load sharing properties of
      two semiconstrained cervical (Premier and Zephir) plates. OBJECTIVES: To
      determine the percent load transmission through these plates and grafts under
      simple axial compression. SUMMARY OF BACKGROUND DATA: No published data exist as
      to the load transmission through these semiconstrained plates. METHODS: Cadaveric
      calf spines were subjected to axial compression loading while instrumented with
      an interbody graft and with the graft plus one of the plates. Load transmission
      was computed through an analysis of the load-displacement data. RESULTS: A mean
      load transmission of 23% was shared by the Premier plate. The Zephir, a more
      constrained plate but still semiconstrained, shared a mean of 32% of the load.
      CONCLUSIONS: The semiconstrained plates tested allow more graft loading than some
      previously tested constrained plates. However, there are differences between the
      research methods used in these studies that provide a less than satisfactory
      comparison.

PMID- 14673364
TI  - An organ culture system for the study of the nucleus pulposus: description of the
      system and evaluation of the cells.
AB  - STUDY DESIGN: The goal of this study was to develop a methodology to maintain
      intervertebral discs in organ culture, thereby preserving tissue architecture and
      metabolic function in a three-dimensional environment. METHODS: Using a
      microdissection technique, intervertebral discs were removed from rat lumbar
      vertebrae. The discs were maintained in organ culture, and cell viability was
      evaluated histochemically and using probes that measured mitochondrial function
      and thiol status. The biosynthetic activity of the cells was evaluated by Western
      blot and RT-PCR analysis. RESULTS: The in vitro organ culture system maintained
      the vitality of the nucleus pulposus cells. Cells exhibited a high membrane
      potential for 1 week. When cells were exposed to carbonyl cyanide 4
      trifluoromethoxy phenylhydrazone, a known protonophore, the fluorescence was
      lost, indicating that the staining was specific for viable cells. In many cells,
      Celltracker Green, probe for reduced thiols, colocalized with the membrane
      potential. Histologic studies revealed that in culture for 1 week, normal nucleus
      pulposus structure was maintained; after this time period, alterations were
      observed. We evaluated the two tissues for characteristic phenotypic markers HIF
      1alpha and MMP-2. We noted that the nucleus pulposus expressed these proteins.
      The RT-PCR profile at 7 days indicated that the cells also expressed collagen
      type II, aggrecan, and decorin. DISCUSSION: Three factors contributed to success
      in maintaining the vitality of the nucleus pulposus in vitro. First, the cells
      were confined within the disc itself; second, the medium was hyperosmotic; third,
      the medium was supplemented with transforming growth factor-beta. The
      fluorescence measurement provided a rapid method for evaluation of the status of
      nucleus pulposus cells. Histologic analysis confirmed that the cells remained
      viable for at least 1 week. Viability in terms of biosynthetic activity was
      further confirmed using RT-PCR and Western blot analysis. We conclude that short
      term intervertebral disc organ culture can be used as a suitable in vitro model
      to study effects of environmental factors linked to disc degeneration and/or
      regeneration.

PMID- 14673366
TI  - Exposure to pulsed magnetic fields enhances motor recovery in cats after spinal
      cord injury.
AB  - STUDY DESIGN: Animal model study of eight healthy commercial cats was conducted.
      OBJECTIVE: To determine whether pulsed electromagnetic field (PMF) stimulation
      results in improvement of function after contusive spinal cord injury in cats.
      SUMMARY OF BACKGROUND DATA: PMF stimulation has been shown to enhance nerve
      growth, regeneration, and functional recovery of peripheral nerves. Little
      research has been performed examining the effects of PMF stimulation on the
      central nervous system and no studies of PMF effects on in vivo spinal cord
      injury (SCI) models have been reported. MATERIALS AND METHODS: PMF stimulation
      was noninvasively applied for up to 12 weeks to the midthoracic spine of cats
      with acute contusive spinal cord injury. The injury was produced using a weight
      drop apparatus. Motor functions were evaluated with the modified Tarlov
      assessment scale. Morphologic analyses of the injury sites and somatosensory
      evoked potential measurements were conducted to compare results between PMF
      stimulated and control groups. RESULTS: There was a significant difference in
      locomotor recovery between the PMF-stimulated and control groups. Although not
      statistically significant, PMF-stimulated spinal cords demonstrated greater
      sparing of peripheral white matter and smaller lesion volumes compared to
      controls. Somatosensory-evoked potential measurements indicated that the PMF
      stimulated group had better recovery of preinjury waveforms than the control
      group; however, this observation also was not statistically significant because
      of the small sample size. CONCLUSIONS: This preliminary study indicates that
      pulsed magnetic fields may have beneficial effects on motor function recovery and
      lesion volume size after acute spinal cord injury.

PMID- 14673367
TI  - Results of skip laminectomy-minimum 2-year follow-up study compared with open
      door laminoplasty.
AB  - STUDY DESIGN: Results of skip laminectomy and open-door laminoplasty for cervical
      spondylotic myelopathy were compared. OBJECTIVES: To verify that skip laminectomy
      is less invasive to the posterior extensor mechanism of the cervical spine
      including the deep extensor muscles than conventional laminoplasty and is
      effective in preventing postoperative problems often seen after conventional
      laminoplasty of the cervical spine such as persisting axial pain, restriction of
      neck motion, and loss of cervical lordosis. SUMMARY OF BACKGROUND DATA: A
      preliminary short-term follow-up study on skip laminectomy demonstrated that the
      procedure successfully prevented such postoperative problems, while achieving
      adequate decompression of the spinal cord. METHODS: Since December 1998, more
      than 100 patients with cervical spondylotic myelopathy underwent skip
      laminectomy, and 43 who were followed for more than 2 years (average of 2 years
      and 6 months) (Group A) were included in this study. Fifty-one patients who
      underwent open-door laminoplasty (Group B) in the authors' institutes before
      December 1998 served as controls. Japanese Orthopaedic Association scores and
      incidence of newly developed or deteriorated axial pain were recorded.
      Preoperative and postoperative ranges of neck motion were measured on lateral
      flexion and extension radiographs. Preoperative and postoperative cervical
      curvature indices were calculated according to Ishihara's method. For
      quantitative analysis of damage to the posterior cervical muscles, atrophy rates
      were calculated from cross-sectional areas of the deep extensor muscles on
      preoperative and postoperative axial magnetic resonance images. RESULTS: Using
      Japanese Orthopaedic Association scores, the average recovery rates were 59.2%
      for Group A and 60.1% for Group B. Only one patient (2%) in Group A had newly
      developed axial pain, whereas 33 patients (66%) in Group B had postoperative
      development or deterioration of axial pain. Postoperative range of neck motion
      averaged 98% of the preoperative measurement in Group A and 61% in Group B. There
      was no significant difference between preoperative and postoperative cervical
      curvature index in Group A, whereas the mean value of postoperative index (16.0)
      was significantly smaller than that of preoperative one (11.8) in Group B (P <
      0.05). The atrophy rate of the deep extensor muscles in Group A averaged 13%,
      whereas that in Group B was 59.9%. CONCLUSIONS: Skip laminectomy was less
      invasive to the posterior extensor mechanism including the deep extensor muscles
      than open-door laminoplasty. This new procedure was effective in preventing
      postoperative morbidities often seen after conventional laminectomy and
      laminoplasty with adequate decompression of the spinal cord.

PMID- 14673368
TI  - Intermediate follow-up after treatment of degenerative disc disease with the
      Bryan Cervical Disc Prosthesis: single-level and bi-level.
AB  - STUDY DESIGN: Prospective, concurrently enrolled, multicenter trials of the Bryan
      Cervical Disc Prosthesis (Medtronic Sofamor Danek, Memphis, TN) were conducted
      for the treatment of patients with single-level and two-level (bi-level)
      degenerative disc disease of the cervical spine. OBJECTIVES: The studies were
      designed to determine whether new functional intervertebral cervical disc
      prosthesis can provide relief from objective neurologic symptoms and signs,
      improve the patient's ability to perform activities of daily living, decrease
      pain, and maintain stability and segmental motion. SUMMARY OF BACKGROUND DATA:
      The concept of accelerated degeneration of adjacent disc levels as a consequence
      of increased stress caused by interbody fusion of the cervical spine has been
      widely postulated. Therefore, reconstruction of a failed intervertebral disc with
      functional disc prosthesis should offer the same benefits as fusion while
      simultaneously providing motion and thereby protecting the adjacent level discs
      from the abnormal stresses associated with fusion. METHODS: Patients with
      symptomatic cervical radiculopathy and/or myelopathy underwent implantation with
      the Bryan prosthesis after a standard anterior cervical discectomy. At scheduled
      follow-up periods, the effectiveness of the device was characterized by
      evaluating each patient's pain, neurologic function, and radiographically
      measured range of motion at the implanted level. RESULTS: Clinical success for
      both studies exceeded the study acceptance criteria of 85%. At 1-year follow-up,
      the flexion-extension range of motion per level: Discectomy and implantation of
      the device alleviates neurologic symptoms and signs similar to anterior cervical
      discectomy and fusion. Radiographic evidence supports maintenance of motion. The
      procedure is safe and the patients recover quickly. At least 5 years of follow-up
      will be needed to assess the long-term functionality of the prosthesis and
      protective influence on adjacent levels.

PMID- 14673369
TI  - Bone morphogenetic protein-2 facilitates expression of chondrogenic, not
      osteogenic, phenotype of human intervertebral disc cells.
AB  - STUDY DESIGN: In vitro experiment using bone morphogenetic protein-2 (BMP-2) and
      human intervertebral disc (IVD) cells. OBJECTIVES: To demonstrate the effect of
      BMP-2 on mRNAs expression (collagen type I, collagen type II, aggrecan, and
      osteocalcin), proteoglycan synthesis, expression of alkaline phosphatase, bone
      nodule formation in human IVD cells. SUMMARY OF BACKGROUND DATA: BMP-2 was widely
      known as a powerful agent for osteoinduction and a crucial growth factor for
      early chondrogenesis and maintenance of cartilaginous phenotype. BMP-2 proved to
      be effective in stimulating proteoglycan synthesis in articular chondrocytes and
      IVD cells. Nevertheless, the effect of BMP-2 on IVD cells, whether chondrogenic
      or osteogenic, was not thoroughly elucidated in transcriptional level and
      histochemical stains. MATERIALS AND METHODS: Human IVDs were harvested and
      enzymatically digested. Then IVD cells were cultured three-dimensionally in
      alginate beads. Osteoblasts were cultured from cancellous bone of ilium for
      histochemical stains. Recombinant human BMP-2 (rhBMP-2) was produced by Chinese
      hamster ovary cells after transduction of BMP-2 cDNA, then concentrated and
      purified. Then IVD cell cultures were exposed to various concentrations of rhBMP
      2. Reverse transcription-polymerase chain reaction for mRNA expression of
      aggrecan, collagen type I, collagen type II, and osteocalcin was performed. Newly
      synthesized proteoglycan was measured by 35S-sulfate incorporation on Sephadex G
      25 M in PD 10 columns. As a histochemical examination, alkaline phosphatase and
      Alizarin red-S stains were used to detect osteogenic marker and bone nodule
      formation, respectively. RESULTS: In the rhBMP-2 treated cultures, there was
      increased newly synthesized proteoglycan (67% in 300 ng/mL and 200% in 1,500
      ng/mL of rhBMP-2) and up-regulated expression of aggrecan, collagen type I, and
      collagen type II mRNA over untreated control. However, rhBMP-2 did not up
      regulate expression of osteocalcin mRNA in the given dose and culture period. IVD
      cell cultures with rhBMP-2 showed no evidence of bone formation in histochemical
      stains, i.e., alkaline phosphatase and Alizarin red-S, while osteoblast culture
      exhibited strong positive stains. CONCLUSIONS: The rhBMP-2 clearly up-regulated
      mRNA expression of chondrogenic components and also stimulated proteoglycan
      synthesis without expression of osteogenic phenotype. Taken together, this study
      raise the possibility of rhBMP-2 can be anabolic agent for regenerating matrix of
      intervertebral disc.

PMID- 14673371
TI  - Validation of T10-T11 finite element model and determination of instantaneous
      axes of rotations in three anatomical planes.
AB  - STUDY DESIGN: A finite element (FE) model of thoracic spine (T10-T11) was
      constructed and used to determine instantaneous axes of rotation (IARs).
      OBJECTIVES: To characterize the locations and loci of IARs in three anatomic
      planes. SUMMARY OF BACKGROUND DATA: The center of rotation is a part of a precise
      method of documenting the kinematics of a spinal segment for spinal stability and
      deformity assessments and for implant devices study. There is little information
      about loci of IARs in thoracic spine. METHODS: A FE model of thoracic spine (T10
      T11) was developed and validated against published data. The validated model was
      then used to determine the locations and loci of IARs in three anatomic planes.
      RESULTS: Within the validated range, The IARs locations and loci were found to
      vary with the applied pure moments. Under flexion and extension pure moments, the
      loci of IARs were tracked anterosuperiorly for flexion and posteroinferiorly for
      extension with rotation between the superior endplate and the geometrical center
      of the inferior vertebra T11. Under left and right lateral bending pure moments,
      the loci were detected to diverge latero-inferiorly from the mid-height of the
      intervertebral disc, then converge medio-inferiorly toward the geometrical center
      of the inferior vertebra T11. For axial rotation, the IARs were located between
      anterior nucleus and anulus and found to diverge in opposite direction latero
      posteriorly with increasing left and right axial torque. CONCLUSIONS: The results
      of IARs would provide further understanding to the kinematics and biomechanical
      responses of the human thoracic spine, which is important for the diagnosis of
      disc degeneration and implant study.

PMID- 14673370
TI  - Human nucleus pulposis can respond to a pro-inflammatory stimulus.
AB  - STUDY DESIGN: Disc tissue obtained from patients undergoing surgery for
      scoliosis, lumbar radiculopathy, and discogenic pain was cultured under basal and
      lipopolysaccharide-stimulated conditions and the medium analyzed for production
      of a range of pro-inflammatory mediators. OBJECTIVES: This study was conducted to
      confirm that the human intervertebral disc is capable of responding to a pro
      inflammatory stimulus and to identify the principal mediators involved in any
      response. SUMMARY OF BACKGROUND DATA: Degenerate human disc tissue has been shown
      to spontaneously secrete a number of pro-inflammatory mediators. The importance
      of these molecules in the pathophysiology of symptomatic disc degeneration is
      increasingly recognized. Human nucleus pulposus has been shown to synthesize
      increased amounts of interleukin (IL)-6, prostaglandin E2 (PGE2), and nitric
      oxide in response to stimulation with IL-1beta. Murine nucleus pulposus
      synthesizes increased amounts of IL-1beta, IL-6, IL-10, and granulocyte
      macrophage colony-stimulating factor in response to lipopolysaccharide
      stimulation. Lipopolysaccharide is a potent inducer of tumor necrosis factor
      alpha (TNF-alpha), which is thought to play an important role in the
      pathophysiology of sciatica. To date, human nucleus pulposus has not been shown
      to secrete TNF-alpha in response to a pro-inflammatory stimulus. METHODS: Human
      disc tissue obtained from patients undergoing surgery for scoliosis, lumbar
      radiculopathy, and discogenic pain was cultured under basal and
      lipopolysaccharide-stimulated conditions and the medium subsequently analyzed for
      a range of pro-inflammatory mediators. RESULTS: None of the specimens produced
      any TNF-alpha, IL-1beta, granulocyte-macrophage colony-stimulating factor, or
      leukotriene B4. Measurable quantities of IL-6, IL-8, PGE2, MCP-1, basic
      fibroblast growth factor, and trans forming growth factor-beta1 were produced by
      a number of specimens. Lipopolysaccharide significantly increased IL-6, IL-8, and
      PGE2 production in both control and degenerate disc tissue. Degenerate disc
      specimens responded more vigorously to lipopolysaccharide stimulation than
      scoliotic specimens. CONCLUSIONS: We conclude that both scoliotic and degenerate
      human nucleus pulposus can respond to an exogenous pro-inflammatory stimulus by
      secreting increased amounts of IL-6, IL-8, and PGE2 but not TNF-alpha and that
      degenerate disc tissue is more sensitive to a pro-inflammatory stimulus than its
      scoliotic counterpart.

PMID- 14673372
TI  - Do you see what I see? Looking at scoliosis surgical outcomes through
      orthopedists' eyes.
AB  - STUDY DESIGN: A prospective study evaluated orthopedists' ratings of preoperative
      and postoperative cosmesis in adolescents undergoing posterior or anterior spinal
      fusion for idiopathic scoliosis. Measures evaluated how orthopedists rated
      outcome in relation to patient satisfaction with the surgical result. SUMMARY OF
      BACKGROUND DATA: The reliability of physician-derived data as a method for
      evaluating scoliosis surgical outcomes has not been sufficiently explored and has
      not been related to patient satisfaction ratings with the postoperative result.
      OBJECTIVES: The purpose of this study was to determine 1) the intrarater and
      interrater reliability estimates of orthopedists' ratings of scoliosis surgical
      outcomes and 2) the association between orthopedists' ratings and patient
      satisfaction ratings with the postoperative cosmesis. METHODS: Six orthopedists
      independently rated preoperative and postoperative color slides for cosmetic
      deformity in 41 patients with adolescent idiopathic scoliosis. Patients rated
      their satisfaction with the postoperative cosmesis 5 to 11 months after surgery.
      RESULTS: The intrarater and interrater reliabilities of orthopedists' assessments
      of scoliosis surgical outcomes ranged from fair to poor. Orthopedists'
      assessments of postoperative shoulder asymmetry significantly correlated with
      patient satisfaction ratings of cosmetic appearance following surgical correction
      of severe curves. Patient satisfaction ratings were unrelated to orthopedists'
      ratings of scar appearance, cosmetic deformity, and preoperative to postoperative
      cosmetic change. CONCLUSIONS: Intrarater and interrater reliability estimates
      were unacceptably low when evaluating spinal surgical outcomes in these 41
      patients. Overall, orthopedists' ratings were not significantly correlated with
      patient satisfaction ratings of the postoperative result.

PMID- 14673374
TI  - Effect of office ergonomics intervention on reducing musculoskeletal symptoms.
AB  - STUDY DESIGN: Office workers invited and agreeing to participate were assigned to
      one of three study groups: a group receiving a highly adjustable chair with
      office ergonomics training, a training-only group, and a control group receiving
      the training at the end of the study. OBJECTIVE: To examine the effect of office
      ergonomics intervention in reducing musculoskeletal symptom growth over the
      workday and, secondarily, pain levels throughout the day. MATERIALS AND METHODS:
      Data collection occurred 2 months and 1 month before the intervention and 2, 6,
      and 12 months postintervention. During each round, a short daily symptom survey
      was completed at the beginning, middle, and end of the workday for 5 days during
      a workweek to measure total bodily pain growth over the workday. Multilevel
      statistical models were used to test hypotheses. RESULTS: The chair-with-training
      intervention lowered symptom growth over the workday (P = 0.012) after 12 months
      of follow-up. No evidence suggested that training alone lowered symptom growth
      over the workday (P = 0.461); however, average pain levels in both intervention
      groups were reduced over the workday. CONCLUSION: Workers who received a highly
      adjustable chair and office ergonomics training had reduced symptom growth over
      the workday. The lack of a training-only group effect supports implementing
      training in conjunction with highly adjustable office furniture and equipment to
      reduce symptom growth. The ability to reduce symptom growth has implications for
      understanding how to prevent musculoskeletal injuries in knowledge workers.

PMID- 14673375
TI  - Schmorl's node developing in the lumbar vertebra affected with metastatic
      carcinoma: correlation magnetic resonance imaging with histological findings.
AB  - STUDY DESIGN: Described is magnetic resonance (MR) imaging of unusual Schmorl's
      node occurring in the lumbar vertebra affected with metastatic carcinoma.
      OBJECTIVE: To know MR features of Schmorl's node with a neoplastic background.
      SUMMARY OF BACKGROUND DATA: Schmorl's nodes occasionally develop in the vertebrae
      affected with metastatic carcinoma; however, their MR images have been rarely
      illustrated. METHODS: The spinal column dissected from a 65-year-old man who died
      of esophageal carcinoma was examined. Specimen radiographs and MR images were
      correlated to histologic sections. RESULTS: T1-weighted spin-echo image revealed
      intervertebral disc displacement into the second lumbar vertebra, which showed
      intermediate signal intensity, and a surrounding area of lower signal intensity.
      Short T1 inversion recovery image exhibited a crescent area of high signal
      intensity surrounding a focus of intermediate signal intensity. CONCLUSIONS: MR
      features consisting of two different signal patterns are characteristic for
      Schmorl's node with a neoplastic background. The conditions should be
      distinguished from Schmorl's nodes in an acute phase, which show similar MR
      features.

PMID- 14673376
TI  - Late spinal cord compression caused by pulled-out thoracic pedicle screws: a case
      report.
AB  - STUDY DESIGN: A case report. OBJECTIVES: To report a late neurologic compromise
      caused by pulling-out of thoracic pedicle screws. SUMMARY OF BACKGROUND DATA:
      Although screw misplacement is quite common, only few neurologic injuries have
      been reported because of penetration of the medial wall of pedicles in the
      thoracic spine. To our knowledge, neurologic compromise caused by pulling-out of
      the screws has not been reported to date. METHODS: A 6-year-old girl with
      congenital muscle fiber type disproportion was posteriorly instrumented (T3 to
      L4) for severe kyphosis. Later, she had a junctional kyphosis over the top of the
      instrument. Her instrumentation was lengthened to T2 by using transpedicular
      screws. During the follow-up period, T2 screws were pulled-out and intruded into
      the canal, causing neurologic compromise. The presenting symptoms, imaging
      studies, and related literature are reviewed in this report. RESULTS: Patient's
      neurologic symptoms subsided after removal of the pedicle screws intruded into
      the spinal canal. CONCLUSIONS: Pulling-out of transpedicular screws inserted at
      T1 or T2 where the pedicles are oriented more medially may cause late neurologic
      compromise caused by intrusion of triangulated screws into the spinal canal.

PMID- 14673377
TI  - Migration of intracranial hemostatic clip into the lumbar spinal canal causing
      sacral radiculopathy: a case report.
AB  - STUDY DESIGN: A case report. OBJECTIVES: A case of spontaneous migration of
      intracranial hemostatic clip into the lumbar spinal canal causing a sacral
      radiculopathy and severe low back pain was presented. SUMMARY OF BACKGROUND DATA:
      Only five cases have been reported in the literature. The first report was
      described by Oyesiku in 1986; thereafter, four cases have been reported. This
      serves as the first report clearly describing the relationship between the
      migrated site of a foreign body and neurologic symptom, as well as achieving a
      remission of symptom after surgical extirpation. METHODS: A patient who had
      received hemostatic clips to the aqueductal stenosis 31 years ago presented with
      low back pain and sacral radiculopathy. Plain radiography, myelography, and
      subsequent CT revealed that a metal foreign body was located in the subarachnoid
      space at L4 level. Laminectomy of L4 and extirpation of the foreign body were
      performed. RESULTS: The foreign body was a hemostatic clip made of cobalt-based
      alloy that had been applied during the previous intracranial surgery. The clip
      irritated the adjoined intrathecal nerve root and possibly caused the adhesive
      arachnoiditis. All symptoms completely disappeared after the extirpation.
      CONCLUSIONS: An uncommon case of an intracranial hemostatic clip migrating into
      the lumbar subarachnoid space as well as causing sacral radiculopathy was
      reported. The surgical extirpation provided an excellent clinical outcome.

PMID- 14673378
TI  - Thoracic neurenteric cyst in a middle aged adult presenting with Brown-Sequard
      syndrome.
AB  - STUDY DESIGN: To report an unusual presentation of a thoracic neurenteric cyst.
      OBJECTIVES: To increase knowledge about the pathogenesis and treatment of
      intraspinal neurenteric cyst. SUMMARY OF BACKGROUND DATA: Intraspinal neurenteric
      cysts (enterogenous cysts) are very rare congenital cysts of endodermal origin.
      The diagnosis usually is established during the first or second decade of life.
      Those cysts are frequently associated with vertebral or spinal cord anomalies and
      dual malformation with mediastinal or abdominal cysts. METHODS: A 50-year-old man
      presented with 1 year of left midthoracic intercostal pain after chest
      compression injury. Several months before admission, he felt left lower extremity
      weakness with right-side numbness. Plain radiography of thoracic spine was normal
      while MRI showed a cystic mass at T7, T8 level ventral to the spinal cord with
      cord compression. The spinal cord was displaced to the posterior more to the
      right side, mimicking hemisection of the left side of the spinal cord. RESULTS:
      Thoracic laminectomy was performed and the intraspinal cyst was removed. The
      pathology report indicated neuroenteric cyst. The postoperative course was
      uneventful and the signs of myelopathy improved immediately. The patient appeared
      well after 2 years of follow-up. CONCLUSIONS: Intraspinal neuroenteric cyst
      without plain vertebral anomaly may occur after trauma in middle aged adult life
      with Brown-Sequard syndrome. Successful treatment requires early recognition of
      those cysts and their associated abnormalities.

PMID- 14673379
TI  - The spine in fibrodysplasia ossificans progressiva: a case report.
AB  - STUDY DESIGN: A case report of fibrodysplasia ossificans progressiva (FOP).
      OBJECTIVES: To report a very rare cause of back pain. SUMMARY OF BACKGROUND DATA:
      FOP is an autosomal dominant disorder with overexpression of bone morphogenetic
      protein 4 and negative HLA B27. Pathognomonic are congenital malformations of the
      big toes. METHODS: The authors report on a patient with FOP who presented with
      back pain at their outpatient clinic. RESULTS: On physical examination, several
      indurated masses were visible and palpable close to the left and right scapula
      and the thoracic spine. These were not tender or painful, nor warmed or inflamed.
      A significantly decreased range of motion of all levels of the spine and the
      shoulder were found. On the radiographs, segmentation defects of the cervical and
      lumbar spine as well as synostoses of the spinal processes were seen. The
      cervical vertebral bodies were small and unusually high. Heterotopic
      ossifications could be discerned in the lumbar postural muscles and the facet
      joints of the spine were ankylosed. Additionally to these findings, on the
      thoracic radiographs ossifications of the muscles of the shoulder girdle could be
      seen. The pathognomonic shortening of the first metatarsal bone and the proximal
      phalanx was bilaterally present. The surface shaded 3D-reconstruction of the
      computed tomography of the trunk showed multiple bulky and confluating
      ossifications of the shoulder girdle. The spinal processes of the thoracic spine
      were anklyosed by massive ossifications of the postural muscles. CONCLUSIONS: In
      FOP, diagnosis can be made by the typical clinical and radiological features.

PMID- 14673382
TI  - Antineutrophil cytoplasmic autoantibodies and pathophysiology: new insights from
      animal models.
AB  - PURPOSE OF REVIEW: Since the discovery of antineutrophil cytoplasmic
      autoantibodies (ANCA) and their association with the occurrence of several types
      of small-vessel vasculitis, a causal relation between the two has been suggested.
      Various in vitro and in vivo experimental data provide indirect evidence in
      support of this view. This article comprises a review of the animal models that
      have been used to investigate the pathogenesis of ANCA-associated vasculitis, and
      focuses on recent developments in this field. RECENT FINDINGS: Xiao et al.
      provide definite proof of the pathogenic potential of ANCA in a novel mouse model
      of myeloperoxidase (MPO)-ANCA-associated vasculitis, in which transfer of
      splenocytes or IgG from MPO-/- mice immunized with murine MPO, to naive wild-type
      or Rag2-/- (lacking mature B and T lymphocytes) mice causes a disease remarkably
      similar to its human counterpart. In addition, preliminary studies by Smyth et
      al. show that immunization of Wistar Kyoto rats with human MPO induces antihuman
      MPO antibodies that cross-react with rat MPO, as well as a disease closely
      resembling human small-vessel vasculitis. Another murine ANCA model is the SCG/Kj
      mouse. A recent publication by Neumann et al., however, puts an important
      limitation on the use of this mouse model for the study of ANCA-associated
      vasculitis, demonstrating multiple immune complex deposits in the spontaneously
      occurring vascular lesions. SUMMARY Recently developed animal models of MPO-ANCA
      associated vasculitis convincingly demonstrate that MPO-ANCA are pathogenic.
      Whether similar strategies can be used to develop an appropriate model for
      proteinase 3-ANCA-associated vasculitis remains to be investigated.

PMID- 14673383
TI  - Clinical applications of antineutrophil cytoplasmic antibody testing.
AB  - PURPOSE OF REVIEW: Antineutrophil cytoplasmic antibodies are closely associated
      with Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome
      and have contributed to new pathogenetic concepts and improved nomenclature of
      systemic vasculitides (antineutrophil cytoplasmic antibody-associated
      vasculitides). However, the application of antineutrophil cytoplasmic antibody
      testing as a clinical diagnostic tool is still regarded as controversial. This
      review summarizes the most recent developments in the field, identifies areas of
      uncertainty, and gives practical guidelines. RECENT FINDINGS: The problems of
      antineutrophil cytoplasmic antibody testing include the diversity of
      antineutrophil cytoplasmic antibody target antigens, assay standardization and
      performance, the application of antineutrophil cytoplasmic antibody testing in a
      clinical setting with a low pretest probability, and, finally, the widespread
      assumption that antineutrophil cytoplasmic antibody titers alone may closely
      reflect disease activity and therefore may be used to guide therapy. SUMMARY:
      Recent findings demonstrate that the combined use of indirect immunofluorescence
      tests and solid phase assays to detect antineutrophil cytoplasmic antibody
      directed against myeloperoxidase and proteinase 3 can minimize the occurrence of
      false-positive antineutrophil cytoplasmic antibody results. Furthermore, the
      yield of antineutrophil cytoplasmic antibody testing can be improved by the use
      of a well-standardized test, adherence to published guidelines, and restricting
      the use of the tests to clinical situations with a rather high pretest
      probability for antineutrophil cytoplasmic antibody-associated vasculitides.
      However, treatment decisions should be based on the clinical presentation of the
      patient and histologic findings and not on the results of antineutrophil
      cytoplasmic antibody testing alone.

PMID- 14673384
TI  - Recent advances in vascular inflammation: C-reactive protein and other
      inflammatory biomarkers.
AB  - PURPOSE OF REVIEW: Inflammatory vascular diseases are initiated and perpetuated
      by the interaction of immune cells with cells of the affected vessel wall. This
      is directed by a network of chemical messengers, which, in a state of vascular
      health, exist as balanced but opposing forces. Our understanding of this highly
      complex process has advanced significantly in the last several decades. The
      detection of vascular inflammation and monitoring of this activity have long been
      attempted in systemic vasculitis, and, more recently, in atherosclerosis. Markers
      of vascular inflammation used thus far have been of limited value; few provide
      both adequate sensitivity and specificity for any particular disease. New
      insights into the pathophysiology of vascular inflammation have identified other
      potential markers that may improve detection and monitoring of these conditions.
      RECENT FINDINGS: Immunomodulatory mediators of the inflammatory cascade have been
      identified, and their roles are being defined. There are recent data that
      implicate various cytokines, proteases, adhesion molecules, and acute phase
      proteins as participants in the generation of vascular inflammation. CONCLUSION:
      The pursuit of highly sensitive and specific markers of vascular inflammation has
      produced a wealth of information that has been instrumental in advancing our
      comprehension of this complex process. Further studies will establish the role of
      these new markers in the diagnosis, monitoring, and prognostication of
      inflammatory vascular disease.

PMID- 14673385
TI  - Giant cell arteritis: strategies in diagnosis and treatment.
AB  - PURPOSE OF REVIEW: This review summarizes current diagnostic assessments and
      therapeutic strategies in giant cell arteritis. Giant cell arteritis or temporal
      arteritis is a chronic vasculitis of large and medium-size vessels. Concurrent
      symptoms of proximal muscular ache and morning stiffness, polymyalgia rheumatica,
      are commonly seen. Recent investigations support the contention that polymyalgia
      rheumatica and temporal arteritis are two different expressions of the same
      underlying vasculitic disorder. RECENT FINDINGS: The symptomatology of giant cell
      arteritis is quite varying. Recently a frequent occurrence of audiovestibular
      manifestations was demonstrated, which should be actively searched for in the
      clinical investigation. Although color Doppler ultrasound, MRI, and positron
      emission tomography have illustrated the widespread nature of giant cell
      arteritis, none of these techniques may currently replace temporal artery biopsy.
      Biopsy of the superficial temporal artery is a safe and simple procedure, and
      remains the gold standard for the diagnosis of giant cell arteritis. The
      importance of long biopsies and meticulous histologic examination using sub
      serial sectioning is emphasized. Numerous recent publications confirm the low
      diagnostic yield of a second, contralateral biopsy. Corticosteroids remain the
      cornerstone in the treatment of giant cell arteritis. Although steroid treatment
      promptly eliminates symptoms of systemic inflammation, its effect on inflammatory
      morphology is delayed. Consequently, there is a need for new therapeutic
      strategies. The potential role of aspirin has recently been implicated.

PMID- 14673386
TI  - Diagnostic imaging in Takayasu arteritis.
AB  - PURPOSE OF REVIEW: New imaging modalities may help accurately diagnose and
      monitor Takayasu arteritis (TAK). Examination of the published literature on
      arterial imaging studies other than conventional angiography will help guide
      appropriate use of these studies in TAK. MRI, magnetic resonance angiography
      (MRA), Doppler ultrasound, CT, and positron emission tomography (PET) are all
      potentially useful for evaluation of TAK. RECENT FINDINGS: MRI/A avoids the risks
      of arterial puncture, iodinated contrast load, and radiation exposure, while
      providing information on arterial wall anatomy and obtaining a generalized
      arterial survey in TAK. Ultrasound can be helpful in detecting sub-millimeter
      changes in wall thickness of the carotid arteries and in differentiating TAK from
      atherosclerotic disease based on minimal plaque content, concentric and long
      segmental involvement, and location of lesion. Like MRI, CT angiography can be
      used to detect areas of aortic wall thickening and obtain a generalized survey of
      the aorta and its proximal branches for areas of stenosis and without the risks
      associated with arterial puncture. However, CT provides less detailed resolution
      than ultrasound and incurs the risks of contrast administration. Finally, PET
      scanning may provide valuable information about cellular activity within an
      inflamed arterial wall before morphologic changes on other imaging studies.
      SUMMARY: Although it is still unclear how often early arterial wall changes lead
      to stenotic lesions, use of these modalities in combination, for both routine
      monitoring and evaluation of new symptoms, may facilitate the detection of TAK
      disease activity at a more treatable stage.

PMID- 14673387
TI  - Behcet syndrome.
AB  - PURPOSE OF REVIEW: Interest in Behcet syndrome (BS), although the condition is
      rare in many parts of the world, is increasing as judged by the growing number of
      related publications and scientific meetings. RECENT FINDINGS: Recent work
      reconfirmed the following without further insight into their meaning in
      pathogenesis: males have a more severe course; one third of the patients have a
      thrombophilia; papulopustular lesions and arthritis go together; gammadelta T are
      increased; and HLA B51 is still the main genetic association. Presence of
      increased levels of antibodies to Saccharomyces cerevisiae and the proposal of
      alpha-enolase as the target antigen of antiendothelial cell antibodies, known to
      be present also in BS, are observations that might help in delineating the
      unknown pathogenesis. For management, preliminary yet promising experience with
      the use of anti-tumor necrosis factor agents is being reported. SUMMARY When
      compared with 2 decades ago, we know considerably more and can do more about BS.

PMID- 14673388
TI  - Central nervous system vasculitis in children.
AB  - PURPOSE OF THE REVIEW: To summarize the current literature on central nervous
      system vasculitis in childhood because this condition remains a diagnostic and
      therapeutic challenge. RECENT FINDINGS: Central nervous system vasculitis in
      childhood may be primary or secondary to a variety of conditions including
      infections, collagen vascular diseases, systemic vasculitides, and malignancies.
      Conditions that result in vasospasm or are associated with noninflammatory
      vasculopathies may mimic the features of central nervous system vasculitis.
      Recent studies have described the clinical spectrum of CNS vasculitis in
      childhood. The most common presenting features are headaches and focal neurologic
      deficits. The diagnosis of central nervous system vasculitis remains particularly
      difficult because the available investigative modalities have limited
      sensitivities and specificities. The most helpful diagnostic tests include
      cerebrospinal fluid analysis, MRI of the brain, and angiography. However, brain
      biopsy may be required to diagnose small vessel vasculitis. SUMMARY: This review
      summarizes recent data on primary central nervous system vasculitis and some of
      the secondary CNS vasculitides in children. Awareness of the presenting clinical
      features of CNS vasculitis should lead to consideration of the diagnosis.
      Awareness of the sensitivity and specificity of the various diagnostic tests
      should lead to the more prudent use of invasive diagnostic tests including
      angiography and brain biopsy.

PMID- 14673389
TI  - Rheumatologic manifestations of sarcoidosis.
AB  - PURPOSE OF REVIEW: This review emphasizes the importance of the rheumatological
      signs and symptoms in the presentation of sarcoidosis. Often the presence of
      musculoskeletal findings may lead to the diagnosis of the disease and the
      institution of the appropriate treatment. RECENT FINDINGS: There have been
      significant advances in the treatment of sarcoidosis with the use of biologic
      agents for recalcitrant and severe manifestations of the disease as well as some
      new data regarding pathogenetics and new applications of diagnostic imaging
      studies such as positron emission tomography scanning. SUMMARY: Although
      pulmonary disease is the most frequent manifestation of sarcoidosis,
      musculoskeletal symptoms are not only common, but may be the initial presentation
      of this systemic inflammatory process and could mimic other arthritic and
      autoimmune disorders. This article focuses on the rheumatological aspects of
      sarcoidosis and includes a review of the most recent literature, which shows new
      data on the diagnosis, pathogenesis, and treatment of this condition.

PMID- 14673390
TI  - Relapsing polychondritis.
AB  - SUMMARY: Relapsing polychondritis is a unique, rare autoimmune disorder in which
      the cartilaginous tissues are the primary targets of destruction but the immune
      damage can spread to involve noncartilaginous tissues like the kidney, blood
      vessels, and so forth. The manifestations of the disease can take many different
      forms and the pathogenesis is still unclear. It may occur in a primary form or it
      may be associated with other disease states. This article summarizes important
      aspects of the disease with a focus on recent information regarding clinical
      manifestations, disease associations, pathogenesis, and advances in therapeutics.

PMID- 14673391
TI  - Arthritis in hemochromatosis or iron storage disease.
AB  - PURPOSE OF REVIEW: Hemochromatosis is a common autosomal recessive condition
      characterized by increased iron absorption and tissue deposition. Recognition of
      this condition is important because phlebotomy can be life saving. This review
      examines recent studies of articular manifestations in hemochromatosis and the
      frequency of hemochromatosis genes in the general population and in selected
      patients with various types of arthritis. RECENT FINDINGS: Genetic mutations in
      the HFE gene are present in most patients with hemochromatosis. Several studies
      have shown a higher frequency of homozygous or heterozygous HFE mutations in
      individuals with various types of arthritis compared with unselected populations.
      Although important, the lack of characterization of arthritis in the controls of
      these studies limits their impact. One recent study compared arthritis symptoms
      in individuals with HFE mutations, newly identified through a large screening
      program, with individuals lacking such mutations from the same population.
      Individuals with hemochromatosis genotypes reported a higher frequency of some
      arthritis symptoms than did controls. Although these differences were not
      statistically significant, the low number of individuals with hemochromatosis
      genotypes limited the statistical power of this study. SUMMARY: Arthritis
      symptoms are common in individuals with hemochromatosis and can have a
      significant impact on their quality of life. Although the genetic defect
      associated with hemochromatosis is common in whites, the frequency with which
      these genotypes cause clinical disease remains unclear. More detailed study of
      arthritis symptoms and signs over time in individuals with and without mutations
      in the HFE gene is necessary to determine the contribution of HFE genes to
      arthritis in the population.

PMID- 14673392
TI  - The systemic amyloidoses.
AB  - PURPOSE OF REVIEW: Clinical management of the amyloidoses has historically been
      the province of rheumatologists, because of the relation to long-standing
      inflammation in rheumatoid arthritis, ankylosing spondylitis, and juvenile
      chronic arthritis. Currently, nephrologists, hematologist-oncologists,
      neurologists, and transplant surgeons all have a diagnostic or therapeutic
      interest. Current advances, using the tools of physical biochemistry, cell
      biology, and genetics, have begun to impact the diagnosis and clinical management
      of these disorders and raise questions regarding our notions of protein
      conformation in vivo and how nonnatively folded proteins may produce disease.
      RECENT FINDINGS: It appears that all amyloidogenic precursors undergo some degree
      of misfolding that allows them to populate an immediate precursor pool from which
      they rapidly aggregate. Depending on the particular protein, a variety of
      mechanisms appear operative, some of which involve nonphysiologic proteolysis,
      defective physiologic proteolysis, mutations involving changes in thermodynamic
      or kinetic properties, and pathways that are yet to be defined. Whatever the
      particular process, the result is a tendency toward oligomeric aggregation
      followed by the assembly of higher order structures that become insoluble under
      physiologic conditions. Detailed analyses have been described for transthyretin
      (senile systemic amyloidosis and familial amyloid polyneuropathy), immunoglobulin
      light chains (light-chain amyloid), beta2 microglobulin (dialysis-related
      amyloid), and apolipoprotein A1, and are in process for others. SUMMARY Therapies
      have been proposed based on precursor stabilization (transthyretin), elimination
      of the synthesizing cell (light-chain amyloid), fibril disruption and
      immunization to induce host-mediated aggregate clearance (Alzheimer disease,
      light-chain amyloid, prions), and aggressive therapy of a primary inflammatory
      process (amyloid A). During the next decade, the value of these therapies, and
      others, suggested by studies on the basic properties of cells and proteins, will
      become clear.

PMID- 14673393
TI  - Musculoskeletal features of disorders of lipid metabolism and multicentric
      reticulohistiocytosis.
AB  - PURPOSE OF REVIEW: Musculoskeletal features of hyperlipidemia are well known,
      although rarely encountered by rheumatologists. New data have been collected on
      the beneficial and adverse effects of lipid-lowering drugs, which are of interest
      to rheumatologists. Multicentric reticulohistiocytosis is a rare systemic
      disorder of which joint involvement is an important and frequent feature. Recent
      advances in its pathophysiology and management have been made. RECENT FINDINGS:
      Little has been added to the knowledge about the musculoskeletal features of
      hyperlipidemia in the recent literature. In contrast, the interest in fenofibrate
      for treating hyperuricemia in patients with lipid disorders or in those
      intolerant of allopurinol has been further supported. Muscle toxicity of statins
      continue to retain attention, and the ability of these drugs to induce low-grade
      myopathy, without increasing serum creatine kinase, has been defended.
      Multicentric reticulohistiocytosis has been the subject of a number of articles,
      including reports on the efficacy of cyclosporine and of etanercept in one
      patient each. SUMMARY: Several issues of therapeutic importance are discussed in
      this brief review.

PMID- 14673394
TI  - [Greetings from the newly elected SIAARTI President, Prof. R. Tufano, to all
      Italian anesthesiologists].

PMID- 14673395
TI  - Analgesia and sedation in intensive care: a progress report.

PMID- 14673396
TI  - Neuroanaesthesia: key points during the perioperative period.

PMID- 14673397
TI  - Perioperative thoracic epidural analgesia in aortic surgery: role of
      levobupivacaine.
AB  - AIM: Perioperative pain management in patients undergoing surgery is an essential
      target in order to improve intraoperative outcome and reduce postoperative
      complications occurrence. The combination of a local anesthetic with an opiate
      for epidural administration can ensure both analgesic effect (opiate) and
      neuroendocrine protection (local anesthetic). Levobupivacaine, S(-)-enantiomer
      form of bupivacaine, produces a sensitive-motor blockade similar to the racemate,
      with less cardiotoxicity; also ropivacaine is not cardiotoxic, but it has less
      anesthetic efficacy than levobupivacaine; both anesthetics could be administered
      through the epidural catheter in order to ensure adequate analgesia without any
      hemodynamic effects. Aim of our study was to evaluate a thoracic epidural
      analgesia for abdominal aortic surgery. METHODS: Through a randomized mono-blind
      study, involving 28 patients undergoing aortic surgery, we performed a clinical
      evaluation of 2 different perioperative thoracic epidural analgesic techniques; 2
      different local anesthetics (levobupivacaine versus ropivacaine) in combination
      with the same opiate (fentanyl) were compared. RESULTS: The results obtained show
      that both techniques ensure an excellent perioperative analgesia without any
      cardiotoxicity, with only moderate adverse effects due to opiate; the absence of
      postoperative mortality (within 30 days from operation) and the modest
      perioperative morbidity underline the qualities of this analgesic technique.
      CONCLUSION: The combination of fentanyl with levobupivacaine or ropivacaine for
      use in thoracic epidural administration ensured both analgesic and neuroendocrine
      effect; significative differences between the 2 local anesthetics cannot be
      demonstrated, even if levobupivacaine, which presents a higher anesthetic
      efficacy, requires lower dosages.

PMID- 14673399
TI  - Memory distortion during acute and chronic pain recalling.
AB  - AIM: The aim of this study was to evaluate the presence of pain memory distorsion
      using different quantitative pain scales. METHODS: A retrospective study on 2333
      patients treated in a Pain Therapy Centre from 1994 to 2000 was carried out. VAS
      and NRS scores have been evaluated, as referred by patients, at the beginning and
      at the end of treatment. Moreover pain relief has been evaluated by means of
      correlation between initial and final pain. RESULTS: Patients do not remember
      initial pain correctly, using both VAS and NRS. CONCLUSION: Pain memory
      distorsion is related to pain intensity variation during treatment rather than
      present pain, and it is inversely related to the initial pain intensity. For this
      reason, it is not correct to evaluate pain relief at the end of treatment since
      this procedure can under- or over-estimate the initial pain.

PMID- 14673398
TI  - Use of sedative and analgesic drugs in the first week of ICU stay in high-level
      of-care.
AB  - AIM: The aim of this study was to update the current practice of pharmacological
      sedation and analgesia in Italian intensive care units. METHODS:  DESIGN:
      observational, prospective, cohort study involving consecutive patients admitted
      during 5 months in 1999. PATIENTS were evaluated for the first 7 days of high
      level-of care. SETTING: 45 adult general intensive care units. PATIENTS: 388
      fulfilling enrollment criteria: admission diagnosis out of non-traumatic cerebral
      hemorrage, stroke, respiratory failure in chronic obstructive pulmonary disease
      (COPD), acute lung injury/distress syndrome (ALI/ARDS), polytrauma, head trauma,
      cardiac failure and major abdominal surgery; unit stay longer than 47 hours and
      high-level-of care treatment. RESULTS: Sedation pattern was different among
      diagnosis-groups. No therapy was registered in 18.8% of overall days in
      polytrauma vs 67.6% of cardiac patients. Opioids supply ranged from 10.1% of
      overall days of acute on COPD patients vs 51.4% of polytrauma patients. Propofol
      was the more prescribed drug, followed by opioids and benzodiazepines. Propofol
      was at the top in cerebrovascular disease, ALI/ARDS and COPD; opioids in
      abdominal surgery and trauma, benzodiazepines in cardiac failure. The average
      number of prescribed drugs per day was 1.5 ranging from 1.2 on COPD to 1.7 in
      head trauma. CONCLUSION: Diagnosis influences the pattern of sedation-analgesia
      during high-level-of-care period. Sedation prevalence is reasonably prescribed in
      trauma groups while it remains low in ALI/ARDS, post-operative, cerebrovascular,
      COPD and hearth failure. Particularly opioid use remains limited in post
      operative patients. This surveys shows a poorly standardised sedation approach to
      the different phases of the therapy: induction, short and long-term sedation
      phase.

PMID- 14673400
TI  - Neuraxial blocks and anticoagulant therapy.
AB  - Spinal and peridural anaesthesia has several advantages over general anaesthesia
      due to their low influence to endocrine and metabolic activity and their capacity
      to reduce postoperative surgical complications, intraoperative bleeding and deep
      venous thromboembolism incidence. Nevertheless, these anaesthesiologic techniques
      have a high risk of severe neurological events in patients treated with
      anticoagulant therapies and prophylaxis. However, this complication is rarely
      found in literature. It must be considered that spontaneous haematomas are
      possible, and these are independent of neuraxial blocks but associated to
      intrinsic factors or concomitant therapies. Anaesthetists must know the use and
      pharmacological properties of anticoagulant drugs in order to be able of giving
      up or modifying them during perioperative time, evaluating the risk of bleeding
      episodes and thrombotic events. An analysis of the literature has been made in
      order to establish favourable conditions, risk factors, international guide-lines
      and the real incidence of haemorrhagic complications associated to central blocks
      in patients being treated with drugs that modify their coagulative status. The
      survey of the literature and the international guide-lines shows that neuraxial
      anaesthesia should be performed in selected patients, respecting the free
      intervals of anticoagulant drugs, carrying out a correct postoperative
      neurological monitoring and evaluating, case by case, the risks and benefits of
      the procedure.

PMID- 14673401
TI  - Cytomegalovirus endocarditis. A case report and a review of the literature.
AB  - The authors describe the case of a 75-year-old man admitted to our intensive care
      unit due to coma and respiratory failure; the history revealed a chronic renal
      failure due to an ANCA+ arteritis; subsequently, he developed a thrombotic
      thrombocytopenic purpura which was treated with plasma exchange. During his
      clinical course the patient developed polymicrobial and fungine sepsis and
      ultimately died. The autopsy demonstrated a severe cytomegalovirus endocarditis,
      which is extremely uncommon in non-immunodepressed patients as those receiving a
      solid-organ transplantation.

PMID- 14673402
TI  - [An open letter to Dr. Vincenzo Carpino, AAROI National President].

PMID- 14673403
TI  - Biomechanical measure validation for spinal manipulation in clinical settings.
AB  - OBJECTIVE: To evaluate the validity and fidelity of the Leander 900 Z Series
      treatment table (Leader Health Technologies Corporation, Port Orchard, Wash) with
      an imbedded AMTI force plate (Advanced Mechanical Technology, Inc, Watertown,
      Mass) as a sensing system and to test its ability to quantify small,
      statistically significant changes in biomechanical parameters of spinal
      manipulative therapy (SMT). SETTING: Technology bench testing and Chiropractic
      College. METHODS: Complex forces and moments were applied to the modified
      treatment table, including standardized static and dynamic loads and those
      exerted by chiropractic students when delivering spinal manipulative therapy.
      Manipulation data was postprocessed by a second-order Butterworth filter with a 5
      Hz cutoff frequency. Changes in lumbar spinal manipulative therapy procedures
      performed by chiropractic students were digitally recorded using the sensing
      system at approximately 1-month intervals throughout the course of a trimester of
      training. RESULTS: The system frequency response remains relatively consistent
      over the interval of test loads from 89 N to 222 N and from 53 nm to 133 nm with
      fundamental frequencies 5.9 Hz and higher. Changes in biomechanical parameters,
      including peak amplitude, slope, and duration over time and training, were
      observed in student chiropractic manipulations. Results show a minimum of 18% (P
      =.0723) increase during interval 1 in mean peak amplitude and slope parameters.
      Only a slight (3%) mean reduction of the procedure duration was seen.
      CONCLUSIONS: The results support the fidelity of the sensing system and its
      ability to quantify small, statistically significant changes in biomechanical
      parameters. With this type of instrumentation, it is feasible to assess the skill
      of chiropractic physicians performing spinal manipulative therapy.

PMID- 14673404
TI  - Three-dimensionality of direct contact forces in chiropractic spinal manipulative
      therapy.
AB  - OBJECTIVE: To perform three-dimensional (3-D) manual contact force measurements
      of chiropractic adjustments at the patient-chiropractor interface. METHODS: A new
      hand/palm-held computerized 3-D force measuring system was used to collect 3-D
      force data at the doctor-patient interface (direct measurement) during cervical,
      thoracic, and sacroiliac adjustments by 2 chiropractors on 10 healthy subjects.
      RESULTS: 3-D components of force were significantly greater than matching 1
      dimensional (1-D) perpendicular force components, which have been the standard in
      direct measurement up until now. As well, 3-D components of force were
      significantly different between adjustment levels, suggesting different dynamics
      (kinetics) of adjustment techniques. Force magnitudes and statistically
      significant differences between loading rates and adjustment levels fit in the
      existing body of knowledge of chiropractic adjustment forces. CONCLUSION: To our
      knowledge, this is the first study which presents 3-D force-time histories of
      chiropractic adjustments recorded at the doctor-subject interface. Direct 3-D
      contact force data seem to have the potential to contribute to chiropractic
      research because of a more complete description of this biomechanical aspect of
      daily practice. Results can be used to study novice and experienced
      chiropractors' techniques and permit the development of training and evaluation
      protocols in teaching institutions.

PMID- 14673405
TI  - Validity of compressive leg checking in measuring artificial leg-length
      inequality.
AB  - OBJECTIVE: To determine the accuracy of instrumented prone compressive leg
      checking. DESIGN: Repeated measures (n = 26) on single subjects (n = 3). SETTING:
      Chiropractic college research clinic. METHODS: A pair of surgical boots were
      modified to permit continuous measurement of leg-length inequality (LLI).
      Multiple prone leg-check observations of a blinded examiner on 3 subjects were
      tested against artificial LLI that was created by randomly inserting 0 to 6 1.6
      mm shims in either boot. Accuracy was assessed both within observations (observed
      versus artificial LLI) and between observations (observed versus artificial
      changes in LLI). The intraclass correlation coefficient (ICC), Lin's concordance
      correlation coefficient (CCC), Bland-Altman limits of agreement, and linear
      regression statistics were obtained to determine the reliability and validity of
      compressive leg checking compared to a reference standard. RESULTS: For each shim
      condition, test-retest reliability was excellent (ICC =.85 and CCC = 0.95). The
      95% confidence interval for the limits of agreement for observed versus
      artificial change in LLI was -5.44 to 5.67. The observed and artificial LLI
      shared 87% of their variation within observations (n = 78) and 88% between
      observations (n = 75). The mean examiner error was 1.72 mm and 2.01 mm,
      respectively. CONCLUSION: Compressive leg checking seems highly accurate,
      detecting artificial changes in leg length +/-1.87 mm, and thus possesses
      concurrent validity assessed against artificial LLI. Pre-leg-check and post-leg
      check differences should exceed 3.74 mm to be confident a real change has
      occurred. It is unknown whether compressive leg checking is clinically relevant.

PMID- 14673406
TI  - Neuromechanical characterization of in vivo lumbar spinal manipulation. Part I.
      Vertebral motion.
AB  - OBJECTIVE: To quantify in vivo spinal motions and coupling patterns occurring in
      human subjects in response to mechanical force, manually assisted, short-lever
      spinal manipulative thrusts (SMTs) applied to varying vertebral contact points
      and utilizing various excursion (force) settings. METHODS: Triaxial
      accelerometers were attached to intraosseous pins rigidly fixed to the L1, L3, or
      L4 lumbar spinous process of 4 patients (2 male, 2 female) undergoing lumbar
      decompressive surgery. Lumbar spine acceleration responses were recorded during
      the application of 14 externally applied posteroanterior (PA) impulsive SMTs (4
      force settings and 3 contact points) in each of the 4 subjects. Displacement time
      responses in the PA, axial (AX), and medial-lateral (ML) axes were obtained, as
      were intervertebral (L3-4) motion responses in 1 subject. Statistical analysis of
      the effects of facet joint (FJ) contact point and force magnitude on peak-to-peak
      displacements was performed. Motion coupling between the 3 coordinate axes of the
      vertebrae was examined using a least squares linear regression. RESULTS: SMT
      forces ranged from 30 N (lowest setting) to 150 N (maximum setting). Peak-to-peak
      ML, PA, and AX vertebral displacements increased significantly with increasing
      applied force. For thrusts delivered over the FJs, pronounced coupling was
      observed between all axes (AX-ML, AX-PA, PA-ML) (linear regression, R(2) = 0.35
      0.52, P <.001), whereas only the AX and PA axes showed a significant degree of
      coupling for thrusts delivered to the spinous processes (SPs) (linear regression,
      R(2) = 0.82, P <.001). The ML and PA motion responses were significantly (P <.05)
      greater than the AX response for all SMT force settings. PA vertebral
      displacements decreased significantly (P <.05) when the FJ contact point was
      caudal to the pin compared with FJ contact cranial to the pin. FJ contact at the
      level of the pin produced significantly greater ML vertebral displacements in
      comparison with contact above and below the pin. SMTs over the spinous processes
      produced significantly (P <.05) greater PA and AX displacements in comparison
      with ML displacements. The combined ML, PA, and AX peak-to-peak displacements for
      the 4 force settings and 2 contact points ranged from 0.15 to 0.66 mm, 0.15 to
      0.81 mm, and 0.07 to 0.45 mm, respectively. Intervertebral motions were of
      similar amplitude as the vertebral motions. CONCLUSIONS: In vivo kinematic
      measurements of the lumbar spine during the application of SMTs over the FJs and
      SPs corroborate previous spinous process measurements in human subjects. Our
      findings demonstrate that PA, ML, and AX spinal motions are coupled and dependent
      on applied force and contact point.

PMID- 14673408
TI  - Efficacy of spinal manipulative therapy for low back pain of less than three
      months' duration.
AB  - OBJECTIVES: To review the efficacy of spinal manipulation for low back pain of
      less than 3 months duration. Data sources Randomized clinical trials on spinal
      manipulative therapy for low back pain were identified by searching EMBASE,
      CINAHL, MEDLINE, and the Physiotherapy Evidence Database (PEDro). Study selection
      Outcome measures of interest were pain, return to work, adverse events,
      disability, quality of life, and patient satisfaction with therapy. Data
      extraction Methodological assessment of the trials was performed using the PEDro
      scale. Trials were grouped according to the type of intervention, outcome
      measures, and follow-up time. Where there were multiple studies with sufficient
      homogeneity of interventions, subjects, and outcomes, the results were analyzed
      in a meta-analysis using a random effects model. Data synthesis Thirty-four
      papers (27 trials) met the inclusion criteria. Three small studies showed spinal
      manipulative therapy produces better outcomes than placebo therapy or no
      treatment for nonspecific low back pain of less than 3 months duration. The
      effects are, however, small. The findings of individual studies suggest that
      spinal manipulative therapy also seems to be more effective than massage and
      short wave therapy. It is not clear if spinal manipulative therapy is more
      effective than exercise, usual physiotherapy, or medical care in the first 4
      weeks of treatment. CONCLUSIONS: Spinal manipulative therapy produces slightly
      better outcomes than placebo therapy, no treatment, massage, and short wave
      therapy for nonspecific low back pain of less than 3 months duration. Spinal
      manipulative therapy, exercise, usual physiotherapy, and medical care appear to
      produce similar outcomes in the first 4 weeks of treatment.

PMID- 14673407
TI  - Neuromechanical characterization of in vivo lumbar spinal manipulation. Part II.
      Neurophysiological response.
AB  - OBJECTIVE: To simultaneously quantify vertebral motions and neuromuscular and
      spinal nerve root responses to mechanical force, manually assisted, short-lever
      spinal manipulative thrusts. METHODS: Four patients underwent lumbar
      laminarthrectomy to decompress the central spinal canal and neuroforamina, as
      clinically indicated. Prior to decompression, finely threaded, 1.8-mm diameter
      intraosseous pins were rigidly fixed to the lumbar spinous process (L1 or L3)
      using fluoroscopic guidance, and a high-frequency, low-noise, 10-g, triaxial
      accelerometer was mounted to the pin. Following decompression, 4 needle
      electromyographic (nEMG) electrodes were inserted into the multifidus musculature
      adjacent to the pin mount bilaterally, and 2 bipolar platinum electrodes were
      cradled around the left and right S1 spinal nerve roots. With the spine exposed,
      spinal manipulative thrusts were delivered internally to the lumbosacral spinous
      processes and facet joints and externally by contacting the skin overlying the
      respective spinal landmarks using 2 force settings ( approximately 30 N, < 5
      milliseconds (ms); approximately 150 N, < 5 ms) and 2 force vectors
      (posteroanterior and superior; posteroanterior and inferior). RESULTS: Spinal
      manipulative thrusts resulted in positive electromyographic (EMG) and compound
      action potential (CAP) responses that were typically characterized by a single
      voltage potential change lasting several milliseconds in duration. However,
      multiple EMG and CAP discharges were observed in numerous cases. The temporal
      relationship between the initiation of the mechanical thrust and the
      neurophysiologic response to internal and external spinal manipulative therapy
      (SMT) thrusts ranged from 2.4 to 18.1 ms and 2.4 to 28.6 ms for EMG and CAP
      responses, respectively. Neurophysiologic responses varied substantially between
      patients. CONCLUSIONS: Vertebral motions and resulting spinal nerve root and
      neuromuscular reflex responses appear to be temporally related to the applied
      force during SMT. These findings suggest that intersegmental motions produced by
      spinal manipulation may play a prominent role in eliciting physiologic responses.

PMID- 14673409
TI  - A suspected case of ulnar tunnel syndrome relieved by chiropractic extremity
      adjustment methods.
AB  - BACKGROUND: There has been little published about ulnar tunnel syndrome (UTS) as
      it relates to the practice of chiropractic, despite chiropractors' apparent
      interest in nerve compression syndromes and a growing trend toward providing
      chiropractic extremity care. This syndrome is not very common and could be
      mistaken for carpal tunnel syndrome by practitioners who are not aware of the
      differences. OBJECTIVE: To discuss the case of a patient with ulnar tunnel
      syndrome whose symptoms were resolved by chiropractic extremity adjustment.
      Clinical features A 45-year-old female patient complained of numbness in her
      little finger. Standard orthopedic testing procedures for the wrist and hand
      reproduced the symptom, but tests for the cervical spine and thoracic outlet
      region were negative. Intervention and outcome Care for this patient consisted of
      adjustment procedures directed to the wrist, primarily the hamate and pisiform
      articulations with the triquetrum. Her symptoms were resolved in 4 office visits,
      with corresponding improvement in examination findings. CONCLUSIONS: This case
      report represents what a patient could expect during a typical chiropractic
      treatment. The examination and the care given were simple and cost-effective but
      might not be sufficient for a more complicated or persistent case. The costs for
      the care in this case were borne solely by the patient and were affordable. Hard
      conclusions cannot be reached without more sophisticated diagnostic procedures,
      additional similar cases, and controlled research conditions.

PMID- 14673410
TI  - Evaluation of axial and flexural stresses in the vertebral body cortex and
      trabecular bone in lordosis and two sagittal cervical translation configurations
      with an elliptical shell model.

PMID- 14673412
TI  - Cervical radiculopathy treated with chiropractic flexion distraction
      manipulation: A retrospective study in a private practice setting.
AB  - BACKGROUND: Although flexion distraction performed to the lumbar spine is
      commonly utilized and documented as effective, flexion distraction manipulation
      performed to the cervical spine has not been adequately studied. OBJECTIVE: To
      objectively quantify data from the Visual Analogue Scale (VAS) to support the
      clinical judgment exercised for the use of flexion distraction manipulation to
      treat cervical radiculopathy.Design and setting A retrospective analysis of the
      files of 39 patients from a private chiropractic clinic that met diagnostic
      criteria for inclusion. All patients were diagnosed with cervical radiculopathy
      and treated by a single practitioner with flexion distraction manipulation and
      some form of adjunctive physical medicine modality. Main outcome measures The VAS
      was used to objectively quantify pain. Of the 39 files reviewed, 22 contained an
      initial and posttreatment VAS score and were therefore utilized in this study.
      RESULTS: This study revealed a statistically significant reduction in pain as
      quantified by visual analogue scores. The mean number of treatments required was
      13.2 +/- 8.2, with a range of 6 to 37. Only 3 persons required more treatments
      than the mean plus 1 standard deviation. CONCLUSION: The results of this study
      show promise for chiropractic and manual therapy techniques such as flexion
      distraction, as well as demonstrating that other, larger research studies must be
      performed for cervical radiculopathy.

PMID- 14673413
TI  - Complex knee reconstruction: articular cartilage treatment options.

PMID- 14673414
TI  - The role of osteotomy in the multiple ligament injured knee.

PMID- 14673415
TI  - Revision anterior cruciate ligament surgery.

PMID- 14673416
TI  - Evaluation and treatment of the multiple ligament injured knee.

PMID- 14673417
TI  - The overhead athlete: examination, testing, and treatment of shoulder
      instability.

PMID- 14673418
TI  - Evaluation of the overhead athlete: Examination and ancillary testing.

PMID- 14673419
TI  - The overhead athlete: how to examine, test, and treat shoulder injuries. Intra
      articular pathology.

PMID- 14673420
TI  - The use of musculoskeletal allograft tissue in knee surgery.

PMID- 14673421
TI  - Arthroscopic allograft surgery of the knee and shoulder: indications, techniques,
      and risks.

PMID- 14673422
TI  - The anatomy, pathology, and definitive treatment of rotator interval lesions:
      current concepts.

PMID- 14673423
TI  - Throwing injuries: diagnosis and treatment.

PMID- 14673424
TI  - Arthroscopic management of anterior, posterior, and multidirectional shoulder
      instability: pearls and pitfalls.

PMID- 14673425
TI  - Arthroscopic approach to traumatic anterior shoulder instability.

PMID- 14673426
TI  - Posterior shoulder instability.

PMID- 14673427
TI  - Innovations in arthroscopic surgery of the shoulder: advances in arthroscopic
      shoulder stabilization.

PMID- 14673428
TI  - Unicompartmental osteoarthritis in the active patient: the role of high tibial
      osteotomy.

PMID- 14673429
TI  - Repicci II unicompartmental knee arthroplasty.

PMID- 14673430
TI  - UniSpacer.

PMID- 14673431
TI  - Nonoperative and arthroscopic approaches to the postmeniscectomy arthritic knee.

PMID- 14673432
TI  - Autologous chondrocyte implantation of the talus.

PMID- 14673433
TI  - The diagnosis and management of osteochondral lesions of the talus: osteochondral
      allograft update.

PMID- 14673434
TI  - New frontiers in articular cartilage injury.

PMID- 14673435
TI  - Treatment of large full-thickness chondral defects of the knee with autologous
      chondrocyte implantation.

PMID- 14673436
TI  - The biological treatment of focal articular cartilage lesions in the knee: future
      trends?

PMID- 14673437
TI  - Current concepts in meniscus surgery: resection to replacement.

PMID- 14673438
TI  - Arthroscopic management of partial, full-thickness, and complex rotator cuff
      tears: indications, techniques, and complications.

PMID- 14673439
TI  - Practice management II: update on ancillary services.

PMID- 14673440
TI  - Regulation of ancillary services.

PMID- 14673441
TI  - The tendon treatment center: new horizons in the treatment of tendinosis.

PMID- 14673442
TI  - Controversies in arthroscopic shoulder surgery: arthroscopic versus open bankart
      repair, thermal treatment of capsular tissue, acromioplasties--are they
      necessary?

PMID- 14673443
TI  - Rotator cuff repair with or without acromioplasty.

PMID- 14673446
TI  - Hip arthroscopy in the presence of dysplasia.
AB  - PURPOSE: Intra-articular pathology of the hip is often associated with dysplasia.
      The presence of dysplasia is often believed to be a harbinger of poor results for
      arthroscopy. The purpose of this study was to report the results of operative hip
      arthroscopy in conjunction with dysplastic disease of the hip. TYPE OF STUDY:
      Prospective clinical case series. METHODS: All patients undergoing hip
      arthroscopy are prospectively assessed with a modified Harris hip score performed
      preoperatively and postoperatively at 3, 12, 24, and 60 months. A minimum of 1
      year follow-up has currently accumulated for 184 consecutive cases. The center
      edge (CE) angle of Wiberg is measured on the anteroposterior pelvis film and
      categorized as normal (> 25 degrees ), dysplastic (< 20 degrees ), or borderline
      dysplasia (20 degrees -25 degrees ). RESULTS: In this study, 48 patients were
      identified with either dysplasia (16) or borderline dysplasia (32). At an average
      of 27 months, 100% follow-up was noted. For the dysplastic group, the average
      preoperative score was 57 and postoperative score was 83. For borderline
      dysplasia, the average preoperative score was 50 and postoperative score was 77.
      Statistically, no difference was found between the 2 groups. Collectively, the
      average improvement was 27 points, with 79% (38 patients) of patients showing at
      least a 10-point improvement. CONCLUSIONS: The results of arthroscopy in the
      presence of dysplasia compare favorably with the general population previously
      reported. The response to treatment is probably dictated more by the nature of
      the intra-articular pathology rather than simply the presence or absence of
      radiographic evidence of dysplasia.

PMID- 14673447
TI  - Osteochondral lesions of the talar dome associated with trauma.
AB  - PURPOSE: The purpose of this study was to clarify the differences in the causes
      of osteochondral lesions (OCL) of the ankle based on the presence of distal
      fibular fractures and lateral instability of the ankle. TYPE OF STUDY: Case
      series. METHODS: We evaluated 92 cases of distal fibular fractures and 86 cases
      of lateral instability of the ankle, including 36 feet with subacute lateral
      instability of the ankle and 50 feet with chronic lateral instability of the
      ankle. In diagnosing OCL, we used a combination of magnetic resonance imaging to
      evaluate the subchondral conditions and ankle arthroscopy to evaluate the
      chondral conditions. RESULTS: Of a total of 92 distal fibular fractures, 65 cases
      (70.7%) had OCL at the time of osteosynthesis and 27 did not (29.3%). Among the
      latter group, 2 developed OCL about 1 year after surgery. Of a total of 86 cases
      of lateral instability of the ankle, 35 (40.7%) had OCL. Among the subacute
      cases, 7 of 36 (19.4%) had OCL, versus 28 of 50 cases (56.0%) with chronic
      lateral instability of the ankle. CONCLUSIONS: Our study suggests that recurrent
      ankle sprains with remaining lateral instability and distal fibular fractures
      could be one of the causes of OCL of the ankle.

PMID- 14673448
TI  - Combined subcoracoid and subacromial impingement in association with
      anterosuperior rotator cuff tears: An arthroscopic approach.
AB  - PURPOSE: The purpose of this study was to evaluate the surgical outcome of
      patients with combined subcoracoid and subacromial impingement with associated
      rotator cuff tears. TYPE OF STUDY: Case series. METHODS: Eight patients with a
      mean age of 63.6 (+/- 8.9) years were reviewed. All patients had combined
      subscapularis, supraspinatus, and infraspinatus tears of the rotator cuff with
      associated subacromial and subcoracoid impingement. All patients were treated
      with arthroscopic subacromial decompression, subcoracoid decompression, and
      rotator cuff repair. RESULTS: At a mean follow-up of 8.8 months (range, 6-12
      months), all patients were satisfied with the procedure. The mean University of
      California Los Angeles (UCLA) score increased from 11.0 +/- 2.6 preoperatively to
      30.9 +/- 2.9 postoperatively (P <.00001). Preoperatively, all patients were in
      the poor category by UCLA criteria. Postoperatively, 2 patients had excellent
      results, 5 patients had good results, and 1 patient had a fair result. All
      patients had significant reduction in pain postoperatively, with 4 patients
      showing complete elimination of pain during all activities. No patient complained
      of pain anteriorly over the coracoid or had positive impingement signs
      postoperatively. Active forward elevation increased from a mean of 103.1 degrees
      +/- 46.5 degrees preoperatively to a mean of 155 degrees +/- 18.5 degrees (P
      <.02). Preoperatively, 4 patients had no active overhead function with positive
      Napoleon tests. Postoperatively, all showed improvement of the Napoleon test and
      regained active overhead function. CONCLUSIONS: Arthroscopic treatment of
      combined subcoracoid and subacromial impingement can lead to good results in this
      patient population. A high index of suspicion for these combined lesions, along
      with adequate surgical decompression and rotator cuff repair, is essential in
      providing pain relief and improved function.

PMID- 14673449
TI  - Acromioclavicular stability: a biomechanical comparison of acromioplasty to
      acromioplasty with coplaning of the distal clavicle.
AB  - PURPOSE: The purpose of the study was to compare the laxity of the
      acromioclavicular (AC) joint in the superior, posterior, and anterior planes
      after isolated acromioplasty and after acromioplasty with inferior clavicular
      coplaning. TYPE OF STUDY: In vitro (cadaveric) analysis. METHODS: Eight fresh
      frozen cadaveric shoulders were evaluated using a hydraulic actuator. While the
      scapula was stabilized, a 30-N force was applied to the distal clavicle
      perpendicular to the AC joint in the superoinferior plane and parallel to the
      joint in the anteroposterior plane. Laxity of the AC joint in the superior,
      anterior, and posterior directions was evaluated via load-displacement analysis
      after acromioplasty and after acromioplasty with coplaning. RESULTS: Coplaning
      the distal clavicle increased superior AC laxity by 53% compared with
      acromioplasty alone (P =.012). With regard to anteroposterior laxity, coplaning
      increased anterior translation by 19% (P =.047) and increased posterior
      translation by 16% (P =.237). Bony impingement was seen to limit posterior
      translation in 3 specimens. CONCLUSIONS: Acromioplasty with coplaning increases
      AC laxity significantly in the superior and anterior directions as compared with
      acromioplasty alone. A trend toward increased posterior translation was found;
      posterior bony impingement may limit posterior laxity.

PMID- 14673450
TI  - Laxity and functional outcome after arthroscopic reduction and internal fixation
      of displaced tibial spine fractures in children.
AB  - PURPOSE: The purpose of this study was to evaluate laxity and functional outcome
      of displaced tibial spine fractures in skeletally immature patients treated with
      arthroscopic reduction and internal fixation. TYPE OF STUDY: Retrospective case
      series. METHODS: Six patients (mean age, 12.0 years old) underwent subjective,
      objective, and instrumented knee laxity assessment at minimum 2 years (mean, 3.2
      years) of follow-up time after arthroscopic reduction and 3.5-mm cannulated screw
      fixation of (Meyers and McKeever type III) tibial spine fractures. RESULTS:
      Physical examination showed persistent laxity, with an abnormal Lachman
      examination in 5 of 6 patients and an abnormal pivot-shift examination in 2 of 6
      patients. Instrumented knee laxity (KT-1000) showed greater than 3-mm manual
      maximum side-to-side difference in 4 of 6 patients. Functional assessment
      revealed excellent function, with a mean Lysholm score of 99.5 (range, 98-100),
      mean Marshall score of 49.0 (range, 47-50), and mean Tegner score of 8.7 (range,
      7-9). CONCLUSIONS: Arthroscopic reduction and internal fixation of type III
      tibial spine fractures in skeletally immature patients results in persistent
      laxity but excellent functional outcome.

PMID- 14673451
TI  - A biomechanical comparison of three lower extremity tendons for ligamentous
      reconstruction about the knee.
AB  - PURPOSE: The purpose of this investigation was to evaluate 3 previously
      unreported allograft tendons for use in knee surgery. These are the doubled
      tibialis anterior (TA), doubled tibialis posterior (TP), and doubled peroneus
      longus (PL) tendons. TYPE OF STUDY: A biomechanical evaluation of the properties
      of the TA, TP, and PL. METHODS: Sixteen fresh-frozen cadaveric lower limbs were
      used for testing. All specimens had the TA, TP, and PL tendons harvested. All
      specimens were tested in a custom-designed hydraulic testing machine using dry
      ice clamps. Each tendon was elongated at a rate of 1 mm/s. Load and displacement
      were recorded with an analog to digital interface board. Stiffness, modulus of
      elasticity, and stress and strain at failure were calculated. RESULTS: The
      average tested lengths of the TA, TP, and PL were 37 cm (range, 13-68 cm), 33 cm
      (range, 7-74 cm), and 42 cm (range, 17-69 cm), respectively. The average cross
      sectional areas of the doubled TA, TP, and PL were 38 mm2, 48 mm2, and 37 mm2,
      respectively. The average failure loads for the doubled TA, TP, and PL tendons
      were 3,412 N, 3,391 N, and 2,483 N, respectively. The maximum stresses of the 3
      tendons did not differ significantly (85-108 Mpa). The TA had the greatest
      stiffness (344 N/mm), followed by the TP (302 N/mm) and the PL (244 N/mm).
      Previous authors have documented the biomechanical strength of grafts for ACL
      reconstruction between 1,700 and 2,900 Newtons. The ultimate tensile strength and
      stiffness reported for the TA and TP grafts exceeded that for all previously
      reported grafts, including the doubled semitendinosus-gracilis. CONCLUSIONS: The
      TA, TP, and PL tendons showed excellent biomechanical properties when compared
      with historical data evaluating other graft sources. The biomechanical properties
      observed for the TA, TP, and PL were noted in specimens despite an average age of
      78.3 years.

PMID- 14673452
TI  - Primary stability of bone-patellar tendon-bone graft fixation with biodegradable
      pins.
AB  - PURPOSE: We evaluated the initial bone-patellar tendon-bone (BPTB) graft fixation
      strength of biodegradable pins compared with interference screws in anterior
      cruciate ligament reconstruction using bovine knees. TYPE OF STUDY: Biomechanical
      in vitro study. METHODS: Ten BPTB grafts from human donors fixed with 2
      biodegradable 2.7-mm pins (Rigid Fix; Ethicon, Mitek Division, Norderstedt,
      Germany) crossing the bone block perpendicular and 10 BPTB grafts fixed with
      conventional biodegradable interference screws (Absolute Absorbable Interference
      Screw; Innovasive Devices, Marlborough, MA) underwent ultimate single-cycle
      failure loading at a rate of 200 mm/min. The grafts were fixed to bovine tibia to
      simulate young human femoral bone density. Failure mode, displacement before
      failure, and ultimate failure load were tested with a testing machine. The
      pullout force was in line with the bone tunnel to simulate a worst case scenario.
      RESULTS: The failure mode for cross pins was either fracture of the bone block (5
      specimens) or fracture of the articular pin (5 specimens). The failure mode for
      interference screws was slippage past the screw in all specimens. In the single
      cycle loading test, the mean yield load for the biodegradable pins was 400.2 (+/-
      122.4) N, maximum load, 524.6 (+/- 136.6) N, with a mean stiffness of 155.2 (+/-
      32.4) N/mm. The yield load at failure for the interference screw was 402.7 (+/-
      143.9) N, maximum load 515.7 (+/- 168.5) N with a mean stiffness of 168 (+/- 42)
      N/mm. CONCLUSIONS: Fixation of a BPTB graft with 2 biodegradable 2.7-mm pins
      (Rigid Fix) leads to primary stability that is comparable to fixation with
      biodegradable interference screws.

PMID- 14673453
TI  - Knee rating scales.
AB  - In the past 2 decades, outcome assessment following knee surgery has focused
      increasingly on the patient's perspective. While traditional measures of outcome,
      including physical examination, imaging studies, and measures of knee laxity are
      complementary, questionnaires have become more important in determining the value
      of a procedure. Reliability, validity, and responsiveness are all important
      measurement qualities for health-related quality of life instruments. There are
      several questionnaires available, both for active patients with disorders of the
      knee, as well as for older patients with degenerative conditions. Activity level
      is also an important prognostic variable for patients with disorders of the knee.
      Clinical researchers should also use a validated activity rating scale to
      evaluate what patients are doing, in addition to how they are doing.

PMID- 14673454
TI  - Scoring systems for the functional assessment of the shoulder.
AB  - A number of instruments have been developed to measure the quality of life in
      patients with various conditions of the shoulder. Older instruments appear to
      have been developed at a time when little information was available on the
      appropriate methodology for instrument development. Much progress has been made
      in this area, and currently an appropriate instrument exists for each of the main
      conditions of the shoulder. Investigators planning clinical trials should select
      modern instruments that have been developed with appropriate patient input for
      item generation and reduction, and established validity and reliability. Among
      the other factors discussed in this review, responsiveness of an instrument is an
      important consideration as it can serve to minimize the sample size for a
      proposed study. The shoulder instruments reviewed include the Rating Sheet for
      Bankart Repair (Rowe), ASES Shoulder Evaluation Form, UCLA Shoulder Score, The
      Constant Score, Disabilities of the Arm, Shoulder and Hand (DASH), the Shoulder
      Rating Questionnaire, the Simple Shoulder Test (SST), the Western Ontario
      Osteoarthritis of the Shoulder Index (WOOS), the Western Ontario Rotator Cuff
      Index (WORC), the Western Ontario Shoulder Instability Index (WOSI), Rotator Cuff
      Quality of Life (RC-QOL), and the Oxford Shoulder Scores (OSS).

PMID- 14673455
TI  - Development of disease-specific quality of life measurement tools.
AB  - Most of the conditions that physicians treat each day impact a patient's quality
      of life rather than the length or quantity of life. In orthopaedic surgery,
      traditional objective measures of patient outcome have included range of motion,
      strength, or radiographic variables. Although these measures have gained wide
      acceptance through their long-standing use, they are usually very poor indicators
      of the functional and psychological aspects of health. It makes sense to measure
      the phenomenon of health-related quality of life when assessing the relative
      efficacies of treatments that are available. If we can accept that health-related
      quality of life is important to measure, the next steps are to understand the
      types of instruments that are available and the appropriate methods by which
      these instruments should be developed and tested. Instruments fall into 2 general
      categories: generic or specific, each with specific advantages and disadvantages.
      The methodology for the development of quality of life tools emphasizes patient
      input and feedback. Determination of validity, reliability, and responsiveness in
      patients similar to those who will participate in trials is an important part of
      establishing the usefulness of an instrument.

PMID- 14673456
TI  - The role of arthroscopy in chronic anterior shoulder dislocation: technique and
      early results.
AB  - Dislocation that lasts longer than 3 weeks is called chronic or unreduced
      shoulder dislocation. Treatment alternatives can be closed reduction, open
      reduction, resection arthroplasty, prosthesis, arthrodesis, and no therapy. The
      English-language literature includes no evidence on arthroscopic reduction for
      the treatment of unreduced shoulder dislocation. The goal of our study was to
      present our technique and period results on the arthroscopic reduction we
      performed in 2 cases 4 and 5 weeks after anterior shoulder dislocation. Reduction
      could not be achieved by closed reduction under anesthesia. With arthroscopic
      visualization, adhesions within the joint were released with blunt dissection.
      Repeat reduction attempts were unsuccessful in these 2 cases. Labroligamentous
      lesions of the inferior glenohumeral ligament were repaired using 3 absorbable
      tacks. On the second day after the surgery, isometric exercises were started. The
      results were evaluated using a 100-unit test recommended by Rowe and Zarins (80
      units in case 1; 85 units in case 2). Reduction of chronic unreduced shoulder
      dislocations using arthroscopy is an alternative technique for selected patients.
      It also allows repair and treatment of the intra-articular pathology in the joint
      and makes early postoperative rehabilitation possible.

PMID- 14673457
TI  - Arthroscopic treatment of symptomatic discoid lateral meniscus in a 26-month-old
      girl.
AB  - Discoid lateral meniscus is a well-documented pathology, but symptomatic discoid
      lateral meniscus in a very young child and arthroscopic management are extremely
      rarely reported. We report a case of symptomatic discoid lateral meniscus in a 26
      month-old girl who showed limping and extension loss after a minor trauma.
      Physical examination revealed clicking and 10 degrees terminal extension loss,
      which was suggestive of the torn discoid meniscus. Magnetic resonance imaging
      showed discoid lateral meniscus with intrameniscal tear. Treatment consisted of
      arthroscopic one-piece excision technique with conventional arthroscopic
      instrument and a No. 11 blade. A good subjective and objective functional outcome
      has been obtained after 35 months of follow-up evaluation.

PMID- 14673458
TI  - Arthroscopic biceps tenodesis using the percutaneous intra-articular transtendon
      technique.
AB  - Traditional management of end-stage pain and degeneration of the proximal biceps
      tendon has included open tenodesis of the biceps tendon. Several methods have
      been described. More recently, however, arthroscopic techniques have been
      developed. This article introduces a novel method of arthroscopic biceps
      tenodesis that does not require any specialized hardware.

PMID- 14673459
TI  - The etiology and assessment of subscapularis tendon tears: a case for subcoracoid
      impingement, the roller-wringer effect, and TUFF lesions of the subscapularis.
AB  - With the advent of arthroscopy and arthroscopic repair techniques, the diagnosis
      and treatment of subscapularis tears have been significantly advanced. The
      precise etiologic factors related to subscapularis tears remain unclear. We
      propose that subcoracoid stenosis and subcoracoid impingement cause a "roller
      wringer effect" on the subscapularis tendon. This effect increases the tensile
      loads on the articular surface of the subscapularis tendon that may lead to
      tensile undersurface fiber failure (TUFF) of the subscapularis insertion.
      Collectively, these factors may in part contribute to the pathogenesis of
      subscapularis tears.

PMID- 14673462
TI  - Mosaicplasty for the treatment of femoral head defect after incorrect resorbable
      screw insertion.
AB  - Articular cartilage lesions and osteochondral defects remain a difficult problem
      for the patient and physician. A variety of procedures and treatments have been
      proposed to lessen symptoms and restore the articular surface. The knee joint has
      been the focus of the vast majority of these cartilage restoration procedures.
      Osteochondral defects of the proximal femur are significantly less common, and
      their management remains poorly defined. This article reports the case of a young
      man with a deep osteochondral defect of the femoral head caused by penetrated
      resorbable screw after internal fixation of a displaced large single fragment of
      the posterior acetabular rim and subsequent treatment using mosaicplasty.

PMID- 14673463
TI  - Juxta-articular myxoma: a rare cause of painful restricted motion of the knee.
AB  - A 68-year-old athletic woman presented to our institution in January 2002 with a
      several-month history of progressing complaints of pain, swelling, and loss of
      motion in the right knee. These manifestations had begun the previous July during
      a game of tennis. She experienced persisting pain and recurring effusions.
      Because the patient had been residing in another state between July and January,
      rheumatologic and orthopaedic evaluations of the knee, including a magnetic
      resonance imaging (MRI), had been performed at a geographically distant (but
      affiliated) institution. The resulting presumptive diagnosis was a "wear and
      tear" degenerative articular disorder of the knee. A program of anti-inflammatory
      medication and physical therapy was begun for several months but produced no
      therapeutic benefit by the time the patient presented at our institution. After
      examination confirmed marked losses of both flexion and extension of the knee,
      effusion, and exquisite medial joint tenderness, an MRI was repeated, using intra
      articular gadolinium as a contrast agent. It revealed an intra-articular mass
      encircling the medial and posterior extents of the medial femoral condyle. An
      arthroscopic multiportal excisional biopsy was performed. It revealed the
      existence of a juxta-articular myxoma. The patient recovered most of the range of
      motion during the next several months, and the effusion and severe pain gradually
      dissipated. The patient was subsequently followed by sequential physical
      examinations and MRIs, performed at increasing intervals of time, without
      recurrence of a mass or of her flagrant symptoms in the first year post surgery.
      Though the patient's diagnosis was established and treatment outcome was
      satisfactory, many issues were brought up in this case regarding most appropriate
      selection of diagnostic tests and treatment approaches.

PMID- 14673464
TI  - Bilateral solid parameniscal masses in the knees.
AB  - Parameniscal cysts of the knee joint are usually considered to be minor
      asymptomatic lesions associated with meniscal injury. We report on a rare case of
      bilateral knee masses in the medial soft tissues that resembled parameniscal
      cysts in terms of location and structure. The patient was an 80-year-old woman
      with severe osteoarthritis. Arthroscopy detected no meniscal tears in either
      knee. Arthrotomy with regional excision of the masses was required. The solid
      masses showed a capsular outer layer that contained fibrin deposits, granulation
      tissue, and fibrous cartilage fragments from the meniscus. We hypothesize that
      these unusual masses represent senescent or "ancient" meniscal cysts, the result
      of long-term fibrous degeneration of previous parameniscal cysts, and may co
      occur with severe osteoarthritis and meniscal degeneration.

PMID- 14673465
TI  - Coronary ligament rupture as a cause of medial knee pain.
AB  - Three cases of a meniscal injury variant are presented, the signs and symptoms of
      which imitate meniscal tear, but that required no definitive intervention and
      resolved with conservative management. We include a review of the literature on
      these injuries. Three patients attended clinic giving a history and exhibiting
      symptoms suggestive of medial meniscal injury. Symptoms were severe and of long
      enough duration to warrant arthroscopic examination of the knees. These patients
      were found to have coronary ligament ruptures. All the patients were treated
      conservatively. The pain resolved in all cases over a few months. No patient
      required a second arthroscopy. The patients were followed up for 9 months in 2
      cases and 2 years in 1 case. By final follow-up examination, all patients were
      symptom free. Meniscal cartilage tear is the most common injury to the knee
      requiring surgery. Standard practice is to diagnose meniscal tear based on
      history and clinical evaluation, and to proceed to arthroscopy if severity of
      symptoms warrants intervention. Although coronary ligament rupture is reported in
      the literature, these reports have been, in the main, arthrographic diagnoses.
      Three case reports with arthroscopic illustration are presented.

PMID- 14673466
TI  - An anterior cruciate ligament and medial collateral ligament tear in a skeletally
      immature patient: a new technique to augment primary repair of the medial
      collateral ligament and an allograft reconstruction of the anterior cruciate
      ligament.
AB  - The goal of this case report is to fill a dual purpose. We describe a case
      involving a tear of the anterior cruciate ligament (ACL) and medial collateral
      ligament (MCL) in a skeletally immature athlete. At the same time, we describe a
      new technique with which we repaired the ACL with an allograft posterior tibialis
      tendon through intra-articular tunnels. A trial of conservative therapy for the
      MCL was performed. During surgery, its instability was assessed. No improvement
      was seen in stability, so a primary repair of the MCL was performed and augmented
      with an autograft gracilis tendon. The patient did well postoperatively,
      subsequently achieving equal stability and range of motion when compared with the
      opposite limb. He was back to competitive sports at 6 months.

PMID- 14673469
TI  - Mutations responsible for 3-phosphoserine phosphatase deficiency.
AB  - We report the identification of the mutations in the only known case of L-3
      phosphoserine phosphatase deficiency, a recessively inherited condition. The two
      mutations correspond to the replacement of the semiconserved Asp32 residue by an
      asparagine and of the extremely conserved Met52 by a threonine. The effects of
      both mutations were studied on the human recombinant enzyme, expressed in
      Escherichia coli. Met52Thr almost abolished the enzymatic activity, whereas the
      Asp32Asn mutation caused a 50% decrease in Vmax. In addition, L-serine, which
      inhibits the conversion of [(14)C] phosphoserine to serine when catalysed by the
      wild-type enzyme, had a lesser inhibitory effect on the Asp32Asn mutant,
      indicating a reduction in the rate of phosphoenzyme hydrolysis. These
      modifications in the properties of the enzyme are consistent with the
      modification in the kinetic properties observed in fibroblasts from the patient.

PMID- 14673470
TI  - Interleukin-1 gene cluster polymorphisms and susceptibility to clinical malaria
      in a Gambian case-control study.
AB  - Interleukin-1 (IL1) is a potent endogenous pyrogen and inducer of the acute phase
      response, and these innate immune responses are an important part of the human
      host's initial reaction to infection by the malaria parasite. In addition,
      several single-nucleotide polymorphisms (SNPs) in this region have previously
      been demonstrated to be associated with susceptibility to infectious disease.
      Therefore, a possible association with malaria susceptibility was investigated. A
      total of 13 polymorphic markers were used in a two-stage screening strategy to
      genotype a Gambian case-control study group by either restriction endonuclease
      digestion or the Sequenom MassARRAY assay. This involved an initial screen of 188
      severe cases and 188 mild controls, and if there was a significant association
      with a malaria phenotype (P<0.05); this was followed by screening of the
      remaining 1044 samples. Two markers showed significant association with malaria:
      interleukin-1 alpha +4845 G --> T (P=0.035 for mild malaria versus controls) and
      interleukin-1 beta +3953 C --> T (P=0.030 for mild malaria versus severe
      malaria). Haplotypes constructed using the SNPHAP programme were not associated
      with any of the malaria phenotypes investigated. In summary, if IL1 variants are
      involved in malaria susceptibility in the Gambia at all, then the effects are
      small.

PMID- 14673471
TI  - A comparative expression analysis of four MRX genes regulating intracellular
      signalling via small GTPases.
AB  - The X chromosomal mental retardation genes have attained high interest in the
      past. A rough classification distinguishes syndromal mental retardation (MRXS)
      and nonsyndromal mental retardation (MRX) conditions. The latter are suggested to
      be responsible for human specific development of cognitive abilities. These genes
      have been shown to be engaged in chromatin remodelling or in intracellular
      signalling. During this analysis, we have compared the expression pattern in the
      mouse of four genes from the latter class of MRX genes: Ophn1, Arhgef6 (also
      called alphaPix), Pak3, and Gdi1. Ophn1, Pak3, and Gdi1 show a specific neuronal
      expression pattern with a certain overlap that allows to assign these signalling
      molecules to the same functional context. We noticed the highest expression of
      these genes in the dentate gyrus and cornu ammonis of the hippocampus, in
      structures engaged in learning and memory. A completely different expression
      pattern was observed for Arhgef6. In the CNS, it is expressed in ventricular
      zones, where neuronal progenitor cells are located. But Arhgef6 expression is
      also found in other non-neural tissues. Our analysis provides evidence that these
      signalling molecules are involved in different spatio-temporal expression domains
      of common signalling cascades and that for most tissues considerable functional
      redundancy of Rho-mediated signalling pathways exists.

PMID- 14673472
TI  - Six novel mutations in the arginine vasopressin gene in 15 kindreds with
      autosomal dominant familial neurohypophyseal diabetes insipidus give further
      insight into the pathogenesis.
AB  - Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is
      caused by postnatal arginine vasopressin (AVP) deficiency resulting from
      mutations in the AVP gene encoding the AVP pre-prohormone. To advance the
      understanding of adFNDI further, we have searched for mutations in the AVP gene
      in 15 unrelated kindreds in which diabetes insipidus appeared to be segregating.
      In nine kindreds, seven different previously described mutations were identified.
      In each of the other six kindreds, unique novel mutations were identified. Two of
      these (225A>G and 227G>A) change a nucleotide in the translation initiation codon
      of the signal peptide, whereas the other four (1797T>C, 1884G>A, 1907T>G, and
      2112C>G) predict amino-acid substitutions in the neurophysin II moiety of the AVP
      prohormone, namely V67A (NP36), G96D (NP65), C104G (NP73), and C116W (NP85).
      Among these, the mutation predicting the V67A (NP36) substitution is remarkable.
      It affects a region of the neurophysin II not affected by any other mutations,
      produces only a minor change, and its inheritance suggests an incomplete
      penetrance. Our findings both confirm and further extend the mutation pattern
      that has emerged in adFNDI, suggesting that the mutations affect amino-acid
      residues known or reasonably presumed to be important for the proper folding
      and/or dimerization of the neurophysin II moiety of the AVP prohormone.

PMID- 14673473
TI  - Haplotypes and DNA sequence variation within and surrounding the transthyretin
      gene: genotype-phenotype correlations in familial amyloid polyneuropathy (V30M)
      in Portugal and Sweden.
AB  - Familial amyloid polyneuropathy (FAP) is a lethal autosomal dominant disorder in
      which fibrils derived from mutant forms of transthyretin (TTR), the normal plasma
      carrier of thyroxine (T(4)) and retinol-binding protein, are deposited in
      tissues. Over 80 TTR sequence variants are associated with FAP, but the amino
      acid substitutions alone do not completely explain the variability in disease
      penetrance, pathology and clinical course. To analyze the factors possibly
      contributing to this phenotypic variability, we characterized the variations
      within the wild-type and mutant (Val30Met) TTR genes and their flanking sequences
      by performing extended microsatellite haplotype analyses, sequencing and single
      nucleotide polymorphism haplotyping of genomic DNA from Portuguese and Swedish
      carriers of V30M. We identified 10 new polymorphisms in the TTR untranslated
      regions, eight resulting from single-base substitutions and two arising from
      insertion/deletions in dinucleotide repeat sequences. The data suggest that the
      onset of symptoms of FAP V30M may be modulated by an interval downstream of TTR
      on the accompanying noncarrier chromosome (defined by microsatellites D18S457 and
      D18S456), but not by the immediately 5'- and 3'-flanking sequences of TTR. During
      the course of these studies, we also encountered the first instance in which the
      previously described intragenic haplotype III may be associated with V30M FAP in
      the Portuguese population.

PMID- 14673474
TI  - Familial Mediterranean fever seems to be not uncommon in Greece.

PMID- 14673475
TI  - Confidentiality and serious harm in genetics - preserving the confidentiality of
      one patient and preventing harm to relatives.
AB  - Genetics can pose special challenges to the principle of confidentiality within
      the health professional-patient relationship, since genetic information is by its
      nature both individual and familial. Most professional guidelines allow
      confidentiality to be broken in rare circumstances, where it will prevent a
      'serious', 'imminent' and 'likely' harm. We argue that the types of harms that
      may result from genetic medicine are particularly diverse. Using clinical
      examples, we explore ethical issues that arise when balancing individual and
      family member interests. As genetic testing becomes more, widespread situations
      will arise where clinicians are faced with a choice between preserving the
      confidentiality of one patient and preventing harm to another. Professionals need
      to incorporate the notion of familial implications in their counseling of
      individuals. Since such dilemmas have been relatively rare in the pre-genetic
      age, we call for a wider debate on the balance between confidentiality and harm
      to others.

PMID- 14673476
TI  - Association of the human adiponectin gene and insulin resistance.
AB  - Adiponectin is an adipocyte-secreted protein that modulates insulin sensitivity
      and whose low circulating concentration is associated with insulin resistance. In
      the present study, we analysed the association between two single-nucleotide
      polymorphisms (SNPs) in the adiponectin gene and insulin resistance in 253
      nondiabetic subjects. In addition, we investigated whether this association is
      modulated by body mass index (BMI) levels. The SNPs +45T>G and +276G>T in the
      human adiponectin gene were detected in real-time PCR with LightCycler. No
      association was found with the +45T>G SNP. The +276G>T SNP was associated with
      higher BMI (P<0.01), plasma insulin (P<0.02) and HOMA(IR) (P<0.02). To analyse
      the possible interaction between BMI and the adiponectin gene on insulin
      resistance, the study group was divided into two subgroups, according to the BMI
      below or above the median of 26.2 kg/m(2). In both subgroups, subjects carrying
      the +276G>T SNP had higher HOMA(IR); however, the difference was highly
      significant among leaner (P<0.001), but not among heavier individuals, indicating
      that BMI status and the adiponectin gene interact in modulating insulin
      resistance. Among individuals with BMI <26.2 kg/m(2), the relative risk of
      insulin resistance was 9.7 (CI: 1.32-87.7, P<0.035). In a subgroup of 67
      subjects, carriers of the +276G>T SNP had significantly (P<0.05) lower mean serum
      adiponectin levels (25.7 ng/ml) compared to noncarriers (37.0 ng/ml), suggesting
      a possible influence of the +276G>T SNP on adiponectin levels. In summary, we
      observed an association between the +276G>T SNP in the adiponectin gene and
      insulin resistance. In particular, among leaner individuals, the adiponectin gene
      appears to determine an increased risk to develop insulin resistance.

PMID- 14673477
TI  - Biparental expression of ESX1L gene in placentas from normal and intrauterine
      growth-restricted pregnancies.
AB  - Equivalent levels of X-linked gene products between males and females are reached
      by means of X chromosome inactivation (XCI). In the human and murine embryonic
      tissues, both the paternally and maternally derived X chromosomes (X(P) and X(M))
      may be inactivated. In murine extra-embryonic tissues, X(P) is imprinted and
      always silenced; humans, unlike mice, can inactivate the X(M) in extra-embryonic
      lineages without an adverse outcome. This difference is probably due to the
      presence of imprinted placental genes on the murine X chromosome, but not on the
      human homologue, essential for placental development and function. An example is
      the paternally imprinted Esx1 gene; mice with a null maternally derived Esx1
      allele show intrauterine growth restriction (IUGR) because of placental
      insufficiency. We investigated the imprinting status of the human orthologous
      Esx1 gene (ESX1L) in placental samples of four normal full-term and 13 IUGR
      female fetuses, in which we determined the XCI pattern. Our findings demonstrated
      that IUGR as well as normal placentas display XCI heterogeneity, thus indicating
      that the IUGR phenotype is not correlated with a preferential pattern of XCI in
      placentas. Moreover, ESX1L is equally expressed in IUGR and normal placentas, and
      shows the same methylation pattern in the presence of both random and skewed XCI.
      These findings provide evidence that ESX1L is not imprinted in human third
      trimester placentas and there is no parent-of-origin effect of chromosome X
      associated with placental insufficiency.

PMID- 14673478
TI  - Susceptibility to pre-eclampsia in Finnish women is associated with R485K
      polymorphism in the factor V gene, not with Leiden mutation.
AB  - This study determines whether genetic variability in the gene-encoding factor V
      contributes to differences in pre-eclampsia susceptibility. Allele and genotype
      frequencies of three single-nucleotide polymorphisms (SNPs) in the factor V gene
      leading to nonsynonymous changes (M385T in exon 8, and R485K and R506Q (Leiden
      mutation) in exon 10) were studied in 133 Caucasian women with pre-eclampsia and
      112 healthy controls. Single-point analysis was expanded to haplotype analysis,
      and haplotype frequencies were estimated using an expectation-maximization
      algorithm. Comparison of single-point allele and genotype distributions of SNPs
      in exons 8 and 10 of the factor V gene revealed statistically significant
      differences in R485K allele (P=0.003) and genotype (P=0.03) frequencies between
      the patients and the control subjects. The A allele of SNP R485K was over
      represented among the patients (12%) vs the control subjects (4%), at an odds
      ratio (OR) of 2.8 (95% confidence interval (CI) 1.2-6.2) for combined A genotypes
      (GA+AA vs GG). Allele and genotype differences between the patients and control
      subjects as regards M385T and Leiden mutation were not significant. In haplotype
      estimation analysis, there was a significantly elevated frequency of haplotype T
      A-G encoding the M385-K485-R506 variant in the pre-eclamptic group vs the control
      group (P=0.01), at an OR of 2.6 (95% CI 1.2-5.5). We conclude that the T-A-G
      haplotype was more frequent among the patient group than in the control group,
      and genetic variations in the factor V gene other than the Leiden mutation may
      play a role in disease susceptibility.

PMID- 14673479
TI  - Approaches to biology teaching and learning: science teaching and learning across
      the school--university divide--cultivating conversations through scientist
      teacher partnerships.

PMID- 14673480
TI  - From the National Academies.

PMID- 14673481
TI  - Fueling education reform: historically black colleges are meeting a national
      science imperative.

PMID- 14673482
TI  - Meeting report: the first National Academies Summer Institute for Undergraduate
      Education in Biology.

PMID- 14673483
TI  - Video views and reviews.

PMID- 14673487
TI  - Is bio2010 the right blueprint for the biology of the future?

PMID- 14673488
TI  - Balancing teaching and research experiences in doctoral training programs:
      lessons for the future educator.
AB  - While a variety of alternative careers has emerged for Ph.D. life scientists in
      industry, business, law, and education in the past two decades, the structure of
      doctoral training programs in many cases does not provide the flexibility
      necessary to pursue career experiences not directly related to a research
      emphasis. Here I describe my efforts to supplement my traditional doctoral
      research training with independent teaching experiences that have allowed me to
      prepare myself for a career that combines both into a combined educational
      program. I describe the issues I have come across in finding and taking part in
      these endeavors, how these issues have affected my work in pursuing my Ph.D., and
      how my experiences translate into my hopes for a future education-based career in
      molecular and cell biology.

PMID- 14673489
TI  - Evolving strategies for the incorporation of bioinformatics within the
      undergraduate cell biology curriculum.
AB  - Recent advances in genomics and structural biology have resulted in an
      unprecedented increase in biological data available from Internet-accessible
      databases. In order to help students effectively use this vast repository of
      information, undergraduate biology students at Drake University were introduced
      to bioinformatics software and databases in three courses, beginning with an
      introductory course in cell biology. The exercises and projects that were used to
      help students develop literacy in bioinformatics are described. In a recently
      offered course in bioinformatics, students developed their own simple sequence
      analysis tool using the Perl programming language. These experiences are
      described from the point of view of the instructor as well as the students. A
      preliminary assessment has been made of the degree to which students had
      developed a working knowledge of bioinformatics concepts and methods. Finally,
      some conclusions have been drawn from these courses that may be helpful to
      instructors wishing to introduce bioinformatics within the undergraduate biology
      curriculum.

PMID- 14673490
TI  - Investigations of protein structure and function using the scientific literature:
      an assignment for an undergraduate cell physiology course.
AB  - Undergraduate biology curricula are being modified to model and teach the
      activities of scientists better. The assignment described here, one that
      investigates protein structure and function, was designed for use in a sophomore
      level cell physiology course at Earlham College. Students work in small groups to
      read and present in poster format on the content of a single research article
      reporting on the structure and/or function of a protein. Goals of the assignment
      include highlighting the interdependence of protein structure and function;
      asking students to review, integrate, and apply previously acquired knowledge;
      and helping students see protein structure/function in a context larger than cell
      physiology. The assignment also is designed to build skills in reading scientific
      literature, oral and written communication, and collaboration among peers.
      Assessment of student perceptions of the assignment in two separate offerings
      indicates that the project successfully achieves these goals. Data specifically
      show that students relied heavily on their peers to understand their article. The
      assignment was also shown to require students to read articles more carefully
      than previously. In addition, the data suggest that the assignment could be
      modified and used successfully in other courses and at other institutions.

PMID- 14673491
TI  - Evaluation of two CD-ROMs from a series on cell biology.
AB  - Two CD-ROMs from a series dealing with various major aspects of cell biology are
      evaluated in this paper using quantitative and qualitative approaches. The
      findings delimit similarities and differences of the two CD-ROMs and shed light
      on how the programs could be used in the learning process and how they should not
      be. The overall impression, as well as the graphical and technical features,
      received a predominantly good rating. The defined target groups were reached
      (e.g., students in secondary schools), different learning approaches were
      supported (e.g., discovery and autonomous learning), the CD-ROMs' usability was
      assessed as being easy and intuitive, and the majority of the evaluators were
      satisfied with the level of interactivity. Navigational problems encountered in
      CD-ROM 1 were overcome by a successful implementation of new navigational
      functions in CD-ROM 2. Most students found the CD-ROM to be a suitable complement
      to, or an extension of, their lessons. We conclude that many, but not all of the
      requirements for the various stages of the learning process could be satisfied
      with the existing CD-ROMs. The requirements not met are discussed to obtain
      insights that could help to improve the production of multimedia learning
      material. The use of quantitative and qualitative approaches in the evaluation of
      learning modules is discussed, as the study began by collecting and analyzing
      anecdotal reviews and was then extended to include a qualitative evaluation.

PMID- 14673492
TI  - Learning biology through research papers: a stimulus for question-asking by high
      school students.
AB  - Question-asking is a basic skill, required for the development of scientific
      thinking. However, the way in which science lessons are conducted does not
      usually stimulate question-asking by students. To make students more familiar
      with the scientific inquiry process, we developed a curriculum in developmental
      biology based on research papers suitable for high-school students. Since a
      scientific paper poses a research question, demonstrates the events that led to
      the answer, and poses new questions, we attempted to examine the effect of
      studying through research papers on students' ability to pose questions. Students
      were asked before, during, and after instruction what they found interesting to
      know about embryonic development. In addition, we monitored students' questions,
      which were asked orally during the lessons. Questions were scored according to
      three categories: properties, comparisons, and causal relationships. We found
      that before learning through research papers, students tend to ask only questions
      of the properties category. In contrast, students tend to pose questions that
      reveal a higher level of thinking and uniqueness during or following instruction
      with research papers. This change was not observed during or following
      instruction with a textbook. We suggest that learning through research papers may
      be one way to provide a stimulus for question-asking by high-school students and
      results in higher thinking levels and uniqueness.

PMID- 14673493
TI  - Apoptosis: a four-week laboratory investigation for advanced molecular and
      cellular biology students.
AB  - Over the past decade, apoptosis has emerged as an important field of study
      central to ongoing research in many diverse fields, from developmental biology to
      cancer research. Apoptosis proceeds by a highly coordinated series of events that
      includes enzyme activation, DNA fragmentation, and alterations in plasma membrane
      permeability. The detection of each of these phenotypic changes is accessible to
      advanced undergraduate cell and molecular biology students. We describe a 4-week
      laboratory sequence that integrates cell culture, fluorescence microscopy, DNA
      isolation and analysis, and western blotting (immunoblotting) to follow apoptosis
      in cultured human cells. Students working in teams chemically induce apoptosis,
      and harvest, process, and analyze cells, using their data to determine the order
      of events during apoptosis. We, as instructors, expose the students to an
      environment closely simulating what they would encounter in an active cell or
      molecular biology research laboratory by having students coordinate and perform
      multiple tasks simultaneously and by having them experience experimental design
      using current literature, data interpretation, and analysis to answer a single
      question. Students are assessed by examination of laboratory notebooks for
      completeness of experimental protocols and analysis of results and for completion
      of an assignment that includes questions pertaining to data interpretation and
      apoptosis.

PMID- 14673494
TI  - Analysis of gene expression in hepatitis B virus transfected cell line induced by
      interferon.
AB  - Infection of hepatitis B virus (HBV) continues to be a significant health
      problem. alpha interferon (IFN-alpha) and gamma interferon (IFN-gamma) have been
      proven to be effective in inhibiting HBV replication. To study the global effect
      of HBV persistent existence on IFN induced cellular gene expression, cDNA
      microarrays dotted with 14 112 human genes were used to examine the
      transcriptional changes between an HBV DNA transfected cell line (HepG2.2.15) and
      its parental cell line (HepG2) after the treatment of IFN-alpha or IFN-gamma for
      6 h. The results showed that many genes related to cell cycle, proliferation,
      apoptosis and new ESTs were regulated by IFN-alpha and/or IFN-gamma. Many genes
      involved in kinase and signal transduction, transcription regulation, antigen
      presentation and processing were differentially regulated between these two cell
      lines post IFN-alpha or IFN-gamma treatment. Interestingly, several IFN
      differentially regulated genes, such as MyD88 and Diubiquitin, were found to
      inhibit HBV gene expression, and MyD88 was proved to inhibit HBV replication.
      Taken together, our results revealed the global effects of HBV persistent
      existence on IFN-induced cellular gene expression. The novel antiviral genes
      identified by microarray could be potentially developed as new anti-HBV drugs or
      for novel therapies.

PMID- 14673495
TI  - Evolution of phenylalanyl-tRNA synthetase by domain losing.
AB  - The gene duplication, fusion and horizontal transfer are the frequent events
      during evolution of many proteins, including the aminoacyl-tRNA synthetases
      (AARSs). However, in this work, it was shown that the main event during evolution
      of phenylalanyl-tRNA synthetase (PheRS) is a domain loss, and the
      function/activity of PheRS is not affected by domain losing. Generally, the size
      of genome and number of genes are increased during evolution from bacteria to
      eukaryote, but the interesting thing is that the type and number of PheRS domains
      in eukaryote are obviously less than those in bacteria. The evolution of PheRS by
      domain losing seems to be related to the functional evolution of some AARSs from
      the multiple specificities to the single specificity.

PMID- 14673496
TI  - Long term gene therapy of Parkinson's disease using immortalized rat glial cell
      line with tyrosine hydroxylase gene.
AB  - Glial cell is an ideal vehicle for gene therapy of brain diseases. However, there
      are many limits in using primary glial cells. Therefore, an immortalized rat
      glial cell line (RGLT) was established by SV40 large T-antigen (LTag) gene from
      the primary rat fetal glial cells. The RGLT cell was shown to be non-tumorigenic
      after transplantation to nude mice (up to 4 weeks) and rat striatum (up to 18
      months). Rat tyrosine hydroxylase (TH) gene was transfected into RGLT cell to
      obtain RGLT-TH cell. The TH immunohistochemical staining and HPLC-ECD analysis
      demonstrated the TH expression and dopamine (DA) production in RGLT-TH cells in
      vitro. When implanting RGLT-TH cells into the striatum of 6-hydroxydopamine (6
      OHDA) lesioned hemiparkinsonism model rats, TH immunohistochemical staining
      showed the TH presence in striatum and HPLC-ECD analysis held at 6 months after
      cell implantation showed an increase of DA content in striatum. The asymmetric
      rotation of rats receiving RGLT-TH cells was reduced by 50%-60% and this
      reduction persisted stably at least for 18 months. These results suggest that the
      immortalized glial cell line could serve as an ideal vehicle for therapeutic gene
      delivery system to achieve a long-term gene therapy of neurodegenerative
      diseases.

PMID- 14673497
TI  - [Construction of N-LMP1 transgenic mice with the specific regulation region in
      nasopharynx].
AB  - In order to elucidate the role of EBV-LMP1 in the nasopharyngeal carcinogenesis,
      the expression vector was constructed with subjecting the N-LMP1 gene to double
      regulation of two specific regulators: EDL-2 and PLUNC-p. The N-LMP1 related
      transgenic mice model has been constructed successfully by pronucleus
      microinjection. 58 founder mice were born, 4 of which were founded to be positive
      by PCR and Southern blot. Immunohistochemistry assay showed that N-LMP1 protein
      was expressed in the nasopharynx, tongue and forestomach of transgenic mice.

PMID- 14673498
TI  - [Effects of oleate on ATP binding cassette transporter A1 expression and
      cholesterol efflux in THP-1 macrophage-derived foam cells].
AB  - To study the effect of oleate on ATP binding cassette transporter A1 (ABCA1)
      expression and cholesterol efflux in THP-1 macrophage-derived foam cells, after
      exposure of the cultured THP-1 macrophage-derived foam cells to oleate for
      different time, cholesterol efflux was determined by FJ-2107P type liquid
      scintillator. ABCA1 mRNA and its protein level were determined by RT-PCR and
      Western blot, respectively. The mean ABCA1 fluorescence intensity of THP-1
      macrophage-derived foam cells was detected by flow cytometry. The results showed
      that oleate markedly inhibited ABCA1-mediated cholesterol efflux from THP-1
      macrophage-derived foam cells. This was accompanied by a reduction in the
      membrane content of ABCA1. Oleate did not alter ABCA1 mRNA abundance, indicating
      that decreased ABCA1 transcription, enhanced mRNA decay, or impaired translation
      efficiency did not account for these inhibitory effects. Oleate, however,
      increased ABCA1 turnover when protein synthesis was blocked by cycloheximide.
      Oleate reduces cholesterol efflux and the level of ABCA1 protein in THP-1
      macrophage-derived foam cells.

PMID- 14673499
TI  - [Cloning and characterization of a novel cardiac-specific kinase gene p93 related
      to sarcomere].
AB  - Myocyte's contraction is regulated by signal transduction pathway composed with
      many protein factors, but the definite mechanism is still uncertain. A novel
      cardiac-specific kinase gene which participates in regulation of signal
      transduction, p93 named, was cloned from adult heart cDNA library. p93, coding a
      family member of MAPKKK, localized on 1p31.1 based on bioinformatics analyses.
      Northern blot and 76-tissue array analyses determined that p93 was merely
      expressed in heart, but was undetectable in other tissues. Immunohistochemical
      study showed that p93 predominantly localized in the nucleus of cardiac myocytes.
      In vitro kinase assay indicated that p93 was a functional kinase capable of
      autophosphorylation. p93 could directly interact with cardiac troponin I by yeast
      two-hybrid system assessed utilizing bait plasmid containing p93 C-terminus (733
      835 aa) and results were further confirmed by co-immunoprecipitation in vivo. Our
      data suggest that p93 is a cardiac-specific kinase and may play important role in
      regulation of sarcomeric contraction protein with signal transduction pathway
      similar ILK.

PMID- 14673500
TI  - [A method for delineation of domains in proteins based on refolding free energy-
      application to continuous and discontinuous domains].
AB  - Domain is a protein architecture in a subunit. It might be defined as a basic
      unit for structure, function, folding, evolution and design. Different
      combinations of domains lead to the formation of various tertiary structures with
      various functions for proteins. The delineation of domains for a protein is
      important both conceptually and practically, which remains up to date a
      challenging and unsolved problem. Based on the above definition, a method was
      previously proposed based on refolding free energy to define continuous domains
      in proteins. By constructing a residue-residue contact matrix, using
      correspondence analysis, and then selecting optimal partition function of a
      protein according to refolding free energy and some empirical scoring functions,
      a new computer program, PDOM, was developed, which was applicable to both
      continuous and discontinuous domains. When compared with the manual partition
      results reported by crystallographers, PDOM has achieved an accuracy of 76% on a
      test data set including 55 protein structures frequently used. The differences in
      13 proteins between PDOM, literature as well as SCOP have been discussed
      extensively.

PMID- 14673501
TI  - [Cloning, expressing and functional analysis of SjMF4, a novel Schistosoma
      japonicum gene].
AB  - Based on the phenomenon of the natural anti-schistosomiasis in Microtus fortis,
      the sera from normal Microtus fortis were employed to immunoscreen the cDNA
      library of adult Schistosoma japonicum (Chinese strain), two positive clones were
      obtained, RACE technique was further applied to amplify one of the clones, and a
      cDNA fragment with an ORF was identified. Sequencing revealed that it was a novel
      gene of Schistosoma japonicum, and it was named SjMF4 (Schistosoma japonicum
      Microtus fortis 4). Then the structure and functional motifs of SjMF4 were
      analysed. The gene was subcloned into pET-28a(+) vector; the recombinant protein
      showed good antigenicity in Western blotting. The gene was further subcloned into
      eukaryotic expression vector pcDNA3 to construct the DNA vaccine containing
      SjMF4. Immune experiments in mice showed significant protection that the
      recombinant plasmid did induce 28.64%+/-3.82% worm reduction and 21.73%+/-3.98%
      egg reduction than controls against the Schistosoma japonicum cercaria challenge.

PMID- 14673502
TI  - [Effects of site-directed mutagenesis at amino acid residues of GATA-1b different
      from that of GATA-1a in Xenopus].
AB  - The GATA-1 of Xenopus (xGATA-1), which has two subtypes xGATA-1a and xGATA-1b, is
      a necessary factor for erythroid differentiation and maturation as similar as
      that of other GATA-1s. Although both xGATa-1a and xGATA-1b are able to stimulate
      erythropoiesis, only xGATA-1b is capable of inhibiting neurogenesis in Xenopus
      embryos. Compared between their structures, xGATA-1a and xGATA-1b are very
      similar in nucleotide and amino acids composition, but not identical. Therefore,
      it is responsible for studying the role of the diverse codons between the two
      genes, so the desired mutations: S(168), H(169) double deletion and point
      mutation of T(304)-->A, T(359)-->A, were introduced into xGATA-1b gene through
      site-directed mutagenesis. Then, mRNA from each mutant as well as wtxGATA-1b was
      co-injected with DN-BR mRNA or separately injected into Xenopus stage 2 embryos,
      and the role of mutants in erythropoiesis and neurogenesis was analyzed by using
      animal cap culture system. The results showed that the neural-inhibiting activity
      of xGATA-1b, but not hematopoiesis-inducing activity, was aborted because of
      deletion of Ser(168) and His(169) or point mutation of T(359)-->A. So it is
      demonstrated for the first time that Ser(168) and His(169) or Thr(359)in xGATA-1b
      may be one of the structural basis for explanting the different function between
      xGATA-1b and xGATA-1a.

PMID- 14673503
TI  - [Cloning and expression of tumor necrosis factor (TNFalpha) cDNA from red
      seabream pagrus major].
AB  - A fragment of TNFalpha cDNA sequence from red seabream was cloned by homology
      cloning approach with two degenerated primers which were designed based on the
      conserved regions of other animals' TNF sequences. The sequence was elongated by
      3' and 5' RACE to get the full length CDS sequence. This sequence contained 1264
      nucleotides that included a 5' UTR of 85 bp, a 3' UTR of 514 bp and an open
      reading frame (ORF) of 666 bp which could encode 222 amino acids propeptide. In
      3' UTR, there were several mRNA instability motifs and three endotoxin-responsive
      sequences, but the sequence lacked the polyadenylation signal. The deduced
      peptide had a clear transmembrane domain, a TNFalpha family signature and a TNF2
      family profile. The cell attachment sequence and the glycosaminoglycan attachment
      sites were also found in the sequence. The red seabream TNF sequence shared
      relatively high similarity with both mammalian TNFalpha and TNFbeta by multiple
      sequence alignments. Phylogenetic analysis showed that the piscine TNFalpha were
      located independently in a different branch compared with mammalian TNFalpha and
      TNFbeta. Based on the primary and secondary structure analysis and gene
      expression study, we could concluded that the red seabream TNF should be a
      TNFalpha, not TNFbeta. RT-PCR was used to study TNFalpha transcript expression.
      24 h after the red seabream was challenged by Vibrio anguillarum, the RS TNFalpha
      transcript expression were detected in blood, brain, gill, heart, head kidney,
      kidney, liver, muscle and spleen. Results showed that TNFalpha mRNA was
      constitutively expressed in parts of the tissues both in stimulated and
      unstimulated fish and the expression could be enhanced after the pathogen
      infection.

PMID- 14673504
TI  - [Effects of sodium selenite on telomerase activity and telomere length].
AB  - To study the biological basis of selenium in resisting senescence through its
      effects on cellular telomerase activity and telomere length. In the experiments,
      the cell line of hepatocytes L-02 was divided into three groups supplemented with
      sodium selenite at final concentrations of 0, 0.5 and 2.5 micromol/L,
      respectively. Cellular telomerase activity was measured by telomeric repeat
      amplification protocol and enzymatic luminometric inorganic pyrophosphate
      detection assay. RT-PCR was used to semi-quantitatively detect human telomerase
      reverse transcriptase (hTERT) gene expression. The change of telomere length was
      assayed through flow cytometry and fluorescence in situ hybridization. Results
      showed that L-02 cells had low telomerase activity and hTERT gene expression
      level when cultured in the normal way. The cells grew well after 3-week
      cultivation in the media supplemented with 0.5 or 2.5 micromol/L sodium selenite.
      Besides, sodium selenite significantly increased cellular telomerase activity and
      hTERT gene expression level. The telomere length of L-02 cells was also extended
      after 4-week-cultivation with sodium selenite. Thus, sodium selenite at
      nutritional doses could prolong the life span of hepatocytes L-02 through
      increasing telomerase activity and telomere length. This result provides a
      possible mechanism for explaining the anti-senescence function of selenium.

PMID- 14673505
TI  - [Cloning, eukaryotic expression and function assay of recombinant leukemia
      inhibitory factor gene LIF].
AB  - Leukemia inhibitory factor (LIF), a cytokine belonging to IL-6 family, which was
      discovered to inhibit the proliferation of murine myeloid leukemic cell line M1,
      has multiple functions in various biological processes. This factor is highly
      glycosylated when it binds to receptor to activate the signal transduction.
      Therefore, expression of LIF through eukaryotic system is the best way to obtain
      the correct glycosylation. In this study, human LIF cDNA with the sequence of
      signal peptide was cloned from adult blood cells by RT-PCR, and then subcloned
      into pcDNA3 for expression in HEK-293T cells. After transfection of the
      recombinant plasmid pcDNA3/LIF into HEK-293T cells, the conditioned medium
      containing the secreted LIF was obtained. The activity of the secreted LIF in the
      conditioned medium was detected through the phosphorylation of STAT3, EMSA and
      luciferase reporter (pGL2-APRE-luc) assays in Hep3B and 293T cells. Furthermore,
      to investigate the biological functions of the overexpressed recombinant LIF, a
      [(3)H]-thymedine incorporation assay was performed, and the results showed that
      the recombinant LIF inhibited the growth of M1 cells strongly. Taken together,
      all the function assays suggest that the recombinant LIF has the normal
      functions, suggesting that the recombinant LIF could be used for further studies.

PMID- 14673506
TI  - [The immunopotentiation of human B lymphocyte stimulator C-terminal peptide].
AB  - The cDNA of human B lymphocyte stimulator C-terminal peptide (C-BLyS) was
      amplified by nested PCR from cDNA library of human fetal brain. The expression
      plasmid pT7450-C-BLyS was constructed and transformed into E. coli BL21 CodonPlus
      (DE3) RIL which can recognize many rare codons. The C-BLyS protein was expressed
      as inclusion body in E. coli BL21 CodonPlus (DE3) RIL and the inclusion body of C
      BLyS was denatured and then refolded by dialysis and purified by ion exchange
      chromatography. The refolded and purified C-BLyS can specifically bind with BCMA
      Fc, a fusion protein of BLyS receptor and human IgG1 Fc. Furthermore, C-BLyS is
      proved to be an effective stimulator in mouse splenocytes proliferation in vitro
      and effective immunostimulant in vivo.

PMID- 14673507
TI  - [Molecular cloning of mTSARG3 gene related to apoptosis in mouse spermatogenic
      cells].
AB  - Beginning from a mouse EST (GenBank Accession No: BE644537) which was
      significantly changed in cryptorchidism and represented a novel gene, GeneScan
      program was performed and a predicted mouse novel gene full-length cDNA sequence
      containing the BE644537 sequence was attained. Gene-specific primers were
      designed for PCR in mouse testis cDNA library. The sequencing result of the PCR
      product showed that we obtain a new gene mTSARG3 (GenBank Accession No: AF419292)
      whose full cDNA length is 1328 bp containing 8 exons and 7 introns. The predicted
      open reading frame encodes a protein of 316 amino acid residues. The protein
      encoded by the new gene is a new member of HSP40 protein family because the
      sequence contains the highly conserved J domain which is present in all DnaJ-like
      proteins and is considered to have a critical role in DnaJ-DnaK protein-protein
      interactions. mTSARG3 protein displays a 46% identity in a 336-amino-acid overlap
      with DJB4-MOUSE protein. The result of RT-PCR analysis and Northern blot showed
      that mTSARG3 is specifically expressed in mouse testis. Southern blot showed that
      there were no loss and rearrangement in cryptorchid. Based upon all these
      observations, it is considered that the function of the new gene is related to
      inhibit mouse testis spermatogenesis apoptosis.

PMID- 14673508
TI  - [Expression, purification and identification of recombinant SARS coronavirus
      membrane protein].
AB  - A novel coronavirus (SARS-coronavirus, SARS-CoV) was discovered as the pathogen
      of the severe acute respiratory syndrome (SARS). According to studies with other
      coronaviruses, the membrane protein (M protein) is the main structural protein
      and the recombinant M protein may be useful as an antigen for detecting
      antibodies against coronavirus and for preparing vaccine. In this work, the M
      protein of SARS-CoV was expressed in E. coli as fusion protein with maltose
      binding protein at N-terminus and MxeGyrA intein CBD at C-terminus. The
      recombinant protein was identified by Western blot and mass spectrometry. The
      soluble parts of the cell crude extract were then partially purified by MBP
      affinity chromatography. The purified protein will be used for the studies on M
      protein's structure and the development of diagnostic method of SARS.

PMID- 14673509
TI  - [Purification of a big defensin from Ruditapes philippinesis and its
      antibacterial activity].
AB  - A novel big defensin was isolated and characterized from the plasma of Ruditapes
      philippinesis. It was purified to homogeneity by means of precipitation with
      (NH(4))(2)SO(4), gel-exclusion chromatography, two kinds of cation-exchange
      chromatography and named RPD-1. Its relative molecular mass was 24.8 kD by means
      of SDS-PAGE. By means of ABI437 amino acid sequence analyser, its 11 NH(2)
      terminal amino acid sequence is AVPDVAFNAYG. Two databank systems (NCBI and
      EBI/EMBL) was indexed, no sequence with homology to RPD-1 was found. Furthermore,
      it exhibited strong inhibition on the growth of Gram-negative and -positive
      bacteria. Minimal inhibitory concentration (MIC) of RPD-1 against Staphylococcus
      aureus, Bacillus subtilis, Micrococcus tetragenus, Escherichia coli, Vibrio
      parahaemolyticus, Vibrio anguillarum was 9.6 mg/L, 76.8 mg/L, 38.4 mg/L, 76.8
      mg/L, 19.2 mg/L, 19.2 mg/L respectively.

PMID- 14673510
TI  - [Prokaryotic expression and characterization of rice Rac protein osRACB].
AB  - As the sole ubiquitous signal GTP-binding protein family in higher plants, Rac
      genes act as pivotal molecular switches and participate in many regulations of
      life activities. In order to study the biochemical characteristics of rice Rac
      protein osRACB, the complete coding sequence of osRACB was cloned into expression
      vector pET28a and expressed in E. coli BL21(DE3). After induced by 1 mmol/L IPTG
      at 37 degrees C for 4 h, the fusion protein His-osRACB was produced in a large
      amount. The fusion protein was purified by Ni(2+)-NTA column and digested by
      thrombin. After a series of processes including separation and recovery by
      electrophoresis, renaturation by glutathione and concentration by
      ultrafiltration, pure osRACB protein in an active form was obtained. The GTP
      binding and hydrolyzing assay showed that osRACB has strong GTP special binding
      and hydrolysis activity regulated by Mg(2+). By comparing it with another rice
      Rac protein osRACD, it can be concluded that osRACB has stronger GTP-binding
      activity and weaker hydrolysis activity than osRACD.

PMID- 14673511
TI  - Endothelium-dependent vascular relaxation induced by Eucommia ulmoides Oliv. bark
      extract is mediated by NO and EDHF in small vessels.
AB  - The vasorelaxant effects of the aqueous extract prepared from the bark of the
      Chinese medicinal herb, Eucommia ulmoides Oliv. (also referred to as Tu-Chung or
      Du-Zhong), which is a common active ingredient in traditional antihypertensive
      herbal prescriptions in China, have recently been characterized in rat aorta and
      dog carotid artery. The vasorelaxant effect of eucommia bark extract on these
      large elastic arteries was found to be entirely endothelium-dependent and nitric
      oxide (NO)-mediated. Since smaller muscular arteries play a more dominant role in
      the change of peripheral resistance and thus the regulation of blood pressure, we
      have now compared the relaxant effects of eucommia bark extract using aorta and
      the proximal as well as the distal ends of the superior mesenteric arteries from
      the rat, with a specific objective to investigate whether smaller muscular
      arteries also elicit endothelium-dependent vascular relaxation (EDVR) in response
      to eucommia bark extract. We have also determined whether the EDVR, if indeed
      occurring in the mesenteric arteries, is mediated entirely by NO, or whether it
      also involves endothelium-derived hyperpolarizing factor (EDHF). We found that
      all three types of vessel preparations elicit EDVR in response to the eucommia
      bark extract concentration-dependently in a similar manner to the relaxant
      responses to carbachol (CCh). Although the NO synthase inhibitor L-NAME totally
      abolished the EDVR in aorta, it only partial abolished EDVR in mesenteric
      arteries isolated from each end, the distal end being more resistant to L-NAME.
      However, the residual L-NAME-resistant relaxation of the rat mesenteric arteries
      could be further inhibited by preincubation of the vessels with the combination
      of L-NAME and 15-20 mM KCl (KCl itself at this low concentration caused little or
      no contraction). Therefore, the EDVR induced by the eucommia extract and CCh in
      aorta is mediated entirely by NO, and that in mesenteric arteries by NO as well
      as EDHF, with the EDHF component (inhibited by KCl) larger in the smaller distal
      end of the rat mesenteric artery. Results of our study offer a plausible
      mechanistic basis for the vasorelaxing action of Eucommia ulmoides Oliv., which
      may account for its well-documented antihypertensive action.

PMID- 14673512
TI  - Further characterization of the 5-HT1 receptors mediating cardiac sympatho
      inhibition in pithed rats: pharmacological correlation with the 5-HT1B and 5-HT1D
      subtypes.
AB  - Serotonin (5-hydroxytryptamine; 5-HT) is capable of inhibiting the tachycardic
      responses elicited by sympathetic stimulation, but not by exogenous
      noradrenaline, in pithed rats pre-treated with desipramine. More recently, it has
      been shown that this cardiac sympatho-inhibitory response to 5-HT, mediated by
      prejunctional 5-HT1 receptors as well as putative 5-ht5A/5B receptors, is
      mimicked dose-dependently by the agonists CP 93,129 (r5-HT1B), sumatriptan (5
      HT1B/1D) and PNU-142633 (5-HT1D). This study analysed further the pharmacological
      profile of the above 5-HT1 receptors. Continuous i.v. infusions of CP 93,129,
      sumatriptan or PNU-142633 (30 micro g kg(-1)min(-1) each) failed to modify the
      tachycardic responses to exogenous noradrenaline but inhibited those elicited by
      preganglionic (C7-T1) stimulation of the cardiac sympathetic outflow. These
      sympatho-inhibitory responses were unaltered after i.v. administration of
      physiological saline (1 ml kg(-1)) or the 5-HT1A receptor antagonist WAY 100635
      (10 micro g kg(-1)). In contrast, the antagonist GR 127935 (5-HT1B/1D; 100 micro
      g kg(-1), i.v.) abolished the responses to CP 93,129, sumatriptan and PNU-142633,
      whilst SB224289 (5-HT1B; 300 micro g kg(-1), i.v.) abolished the responses to CP
      93,129 without affecting those to sumatriptan and PNU-142633. Interestingly,
      BRL15572 (5-HT1D; 300 micro g kg(-1), i.v.) abolished the responses to PNU-142633
      and attenuated those to sumatriptan, but not those to CP 93,129. WAY 100635, GR
      127935, SB224289 and BRL15572, given alone at the above doses, failed to modify
      the sympathetically induced tachycardic responses. The 5-HT1 receptors producing
      cardiac sympatho-inhibition in pithed rats thus display the pharmacological
      profile of the 5-HT1B and 5-HT1D receptor subtypes.

PMID- 14673513
TI  - Protease-activated receptor-2-mediated contraction of urinary bladder is enhanced
      in cyclophosphamide-treated rats.
AB  - Protease-activated receptor-2 (PAR-2) is activated by serine proteases, such as
      trypsin and mast cell tryptase. Recently, we have shown that activators of PAR-2
      contract the rat urinary bladder mainly by stimulating release of prostaglandins
      (PGs) from the mucosal layer. In the present study, we investigated how the PAR-2
      mediated responses are altered in rats with cyclophosphamide (CYP)-induced
      cystitis. The contractile responses to trypsin and PAR-2 activating peptide (PAR
      2 AP; SLIGRL-NH2) in the urinary bladders were augmented by treatment of rats
      with CYP. The contractile effects of these PAR-2 activators on the smooth muscles
      of the urinary bladder were also potentiated after induction of cystitis by CYP.
      On the other hand, CYP-induced cystitis significantly attenuated contractions
      produced by PGE2 in the smooth muscles of the urinary bladder. The PAR-2-mediated
      contractions were significantly prevented by indomethacin or NS-398, an inhibitor
      of cyclooxygenase-2. Both trypsin and PAR-2 AP increased the release of PGE2 from
      the urinary bladder mucosa and smooth muscle. CYP-induced cystitis enhanced the
      PAR-2 activators-induced PGE2 releases from the urinary mucosa without affecting
      those from the smooth muscle of the urinary bladder. The PGE2 releases were
      prevented by indomethacin or NS-398. The mRNAs for PAR-2 in the urinary bladder
      mucosa and smooth muscle preparations were not altered in CYP-induced cystitis.
      These results suggest that PAR-2-mediated responses were enhanced in bladders
      from CYP-treated rats. The enhancement of PAR-2-mediated contraction might be
      ascribed to the increased production of PGs and the altered sensitivity of smooth
      muscle to PAR-2 activators.

PMID- 14673514
TI  - Effects of dizocilpine [(+)-MK-801] on the expression of associative and non
      associative sensitization to D-amphetamine.
AB  - Blockade of glutamate receptors of the NMDA type inhibits the sensitization to
      psychostimulant drugs, such as amphetamine, that occurs after repeated
      administration. Both associative (conditioning) and non-associative (pseudo
      conditioning) mechanisms may contribute to sensitization phenomena. The aim of
      the present study was, thus, to determine which type of sensitization is
      influenced by blockade of NMDA-type receptors by examining the expression
      (manifestation) of sensitization. Locomotor activity was assessed and, in some
      experiments, extracellular dopamine in the nucleus accumbens was also assessed
      using in vivo microdialysis in non-anaesthetized, almost freely moving rats. Male
      albino Wistar rats of 225-250 g were given 1 mg/kg i.p. d-amphetamine every 2nd
      day for 7 days and with saline on the other days. Half the rats were exposed to d
      amphetamine in the presence of conditioning stimuli (test cage, auditory and
      olfactory stimulus) and to saline in the home cage in absence of these stimuli,
      the other half were treated with saline and exposed to the conditioning stimuli
      and were placed into their home cages (without conditioning stimuli) after
      treatment with d-amphetamine. Ten days after the end of this treatment, both
      groups were exposed to the conditioning stimuli and half of each group were
      pretreated with dizocilpine [(+)-MK-801, 0.1 mg/kg i.p.], a blocker of NMDA
      receptors, 30 min before administration of 1 mg/kg d-amphetamine. (+)-MK-801
      reduced the locomotor activity in rats sensitized associatively, but not in those
      sensitized non-associatively. It had no significant effect on spontaneous
      locomotor activity or that induced by acute administration of 1 mg/kg d
      amphetamine. Similarly, (+)-MK-801 inhibited the increase in extracellular
      dopamine in the nucleus accumbens induced by the test dose of d-amphetamine in
      rats sensitized associatively but not non-associatively. The results suggest that
      the expression of both types of sensitization to d-amphetamine are dependent on
      glutamatergic NMDA mechanisms, although in different ways. Inhibition of
      sensitization, in particular of the associative type, might be of therapeutic
      value in drug dependence.

PMID- 14673515
TI  - An attachment tip and pili-like structures in insect- and plant-pathogenic
      spiroplasmas of the class Mollicutes.
AB  - Ultrastructural studies using scanning electron microscopy (SEM), negative
      staining transmission electron microscopy (TEM), and thin-sectioning TEM on four
      species of Spiroplasma, in vitro and/or in vivo, indicated that their helices
      commonly possess one tapered end (tip structure) and one blunt or round end.
      These tip structures appeared morphologically different from the rest of the
      helix, exhibiting an electron-dense conical or rod-shaped core. In thin sections
      of the midgut of the leafhopper Dalbulus elimatus, the tip structures of
      Spiroplasma kunkelii in the midgut lumen were mostly aligned between microvilli,
      perpendicular to the apical plasma membrane of epithelial cells. These tip
      structures appeared frequently attached or closely apposed to the plasma
      membrane, in which cup-shaped invaginations close to the tips were observed.
      Pleomorphic forms of spiroplasma, enclosed in membranous vesicles, were found in
      the cytoplasm of the midgut epithelial cells. These findings suggest that the tip
      structure may be involved in the orientation and attachment of spiroplasma
      helices in relation to their host cells, and thus may be functionally comparable
      to the "attachment organelle" of mycoplasmas. Additionally, pili-like structures
      were observed by negative-staining TEM on the surface of Spiroplasma melliferum,
      and in thin sections of S. kunkelii infecting the leafhopper vector Dalbulus
      gelbus.

PMID- 14673516
TI  - Two-dimensional gel electrophoresis analysis of the abundance of virulent
      exoproteins of group A streptococcus caused by environmental changes.
AB  - Group A streptococci regulate the expression of virulence factors in response to
      environmental change. In order to investigate this mechanism, the growth of group
      A streptococci and the abundance of virulent exoprotein production in culture
      supernatant were analyzed by two-dimensional gel electrophoresis (2-D
      electrophoresis) under several culture conditions. Judging from alterations in
      their growth, group A streptococci were affected by various environmental
      stresses. Under high O(2) and low CO(2 )concentrations, streptococcal pyrogenic
      exotoxin B (SpeB) and streptococcal pyrogenic exotoxin F (SpeF) significantly
      decreased, and the streptococcal inhibitor of complement (Sic) increased. At 30
      degrees C, increases in endo-beta- N-acetylglucosaminidase (EndoS) and alpha
      amylase were also detected, while at 41 degrees C EndoS became undetectable and
      SpeB and SpeF decreased. Sic, SpeF and mitogenic factor 3 (Mf3) decreased when
      cells were cultured in higher NaCl concentrations, and EndoS disappeared
      following culture of the cells in high glucose concentration. An increase in acid
      phosphatase and a decrease in several other proteins were detected when the cells
      were cultivated in high iron concentrations. These results suggest that group A
      streptococci have a versatile adaptation system that responds to several
      environmental stresses by altering the level of exoprotein production.

PMID- 14673517
TI  - Former exercisers of an 18-month intervention display residual aBMD benefits
      compared with control women 3.5 years post-intervention: a follow-up of a
      randomized controlled high-impact trial.
AB  - Exercise is recommended to enhance bone health but data on the maintenance of the
      exercise-induced bone benefit is sparse. The purpose of the study was to assess
      the maintenance of the musculoskeletal benefits obtained in an 18-month
      intervention of high-impact exercise in premenopausal women (34 former trainees
      and 31 controls). Physical performance and areal bone mineral density (aBMD,
      g/cm2) were measured at baseline, after 18 months, and after 5 years. All
      significant 18-month improvements relative to controls in the trainees'
      neuromuscular performance (isometric leg press, and vertical jump with and
      without additional 10% weight of the body mass) had been lost at the 5-year
      follow-up. However, since the changes in aBMD in both former trainees and
      controls by time were similar, the exercise-induced aBMD gain (i.e. the mean
      statistically significant intergroup differences of 1-3% in favor of the
      trainees) was maintained at the femoral neck, distal femur, patella, proximal
      tibia, and calcaneus at the 5-year follow-up. At lumbar spine, the difference was
      1.7% at both 18-month and at the 5-year follow-ups but the difference was not
      statistically significant (NS) in the latter follow-up. At the trochanter and
      unloaded distal radius, the intergroup aBMD differences were NS at both the 18
      month and 5-year follow-ups. In conclusion, the bone sites aBMD increased in
      response to the 18-month intervention, also demonstrated maintenance of this gain
      3.5 years after the intervention. In contrast, the exercise-induced improvements
      in the neuromuscular performance vanished during the post intervention follow-up.
      These findings suggest the possibility of long-term bone benefits of high-impact
      training in women.

PMID- 14673518
TI  - Evidence of myocardial ischaemia in severe scorpion envenomation. Myocardial
      perfusion scintigraphy study.
AB  - OBJECTIVE: To explore the myocardial perfusion by thallium-201 scintigraphy for
      patients with evidence of myocardial damage after scorpion envenomation. DESIGN:
      Prospective study over 1-year period. SETTING: Medical intensive care unit of a
      university hospital (Sfax, Tunisia). PATIENTS: We have prospectively included six
      patients admitted for scorpion envenomation over a period of 1 year in the 22-bed
      intensive care unit (ICU) of our university hospital. The evidence of myocardial
      damage was confirmed by electrocardiography and echocardiography in all patients.
      Myocardial perfusion scintigraphy ((201)Tl scintigraphy) coupled with
      radionuclide ventriculography ((99m)Tc) was performed for all patients, occurring
      32 h on average (range 12-72 h) after the sting. RESULTS: Radionuclide
      ventriculography was abnormal in all cases; the abnormalities observed were
      similar to those observed by echocardiography. Moreover (201)Tl scintigraphy
      showed evidence of myocardial hypoperfusion in all cases. The myocardial
      hypoperfusion grade and localisation were more marked in the abnormal
      localisation shown by echocardiography and electrocardiography, compared to the
      normal wall. Repeated studies, obtained only in two patients within 6 and 15
      days, respectively, showed considerable, but not complete, improvement of wall
      motion and myocardial perfusion. Segments with improved perfusion showed greatly
      improved regional wall motion. CONCLUSION: This study confirms the evidence of
      myocardial hypoperfusion after severe scorpion envenomation.

PMID- 14673519
TI  - Patient State Index (PSI) measures depth of sedation in intensive care patients.
AB  - OBJECTIVE: To investigate whether the electroencephalogram (EEG)-based Patient
      State Index (PSI) indicates the level of sedation as measured by Ramsay score in
      intubated and mechanically ventilated patients in the ICU. DESIGN: Prospective,
      single-blinded observer study. SETTING: Surgical intensive care unit. PATIENTS:
      Forty-one consecutive adult patients requiring intubation and ventilation during
      intensive care therapy. MEASUREMENTS AND RESULTS: Following skin preparation with
      alcohol and placement of EEG electrodes, PSI was recorded while patients were
      ventilated and sedated with constant drug infusion rates. After 30 min, the level
      of sedation was measured by an assessor, who was blinded to PSI values, using the
      Ramsay sedation score. For analysis, the mean of PSI values measured during the
      last minute before clinical assessment of sedation was calculated. General Linear
      Model (GLM) analysis revealed significant differences between the PSI values at
      different levels of sedation as measured by the Ramsay score, except for the
      differentiation of level 5 from levels 4 and 6 (p>0.3) and level 2 from level 3,
      where only a trend was reached (p=0.077). The prediction probability of PSI was
      0.920+/-0.037. CONCLUSION: As the high prediction probability and the analysis of
      paired comparisons suggest, PSI may be used to quantify the level of
      propofol/sufentanil sedation in ICU patients. Further studies are required to
      test whether these promising results can be verified for other drug combinations.

PMID- 14673520
TI  - Effects of terlipressin on systemic and regional haemodynamics in catecholamine
      treated hyperkinetic septic shock.
AB  - OBJECTIVES: To determine the effects of an intravenous bolus dose of a
      vasopressin analogue, terlipressin (1 mg), on systemic haemodynamic parameters
      and gastric mucosal perfusion (GMP) in patients with catecholamine-treated septic
      shock using a gastric tonometry and laser-Doppler flowmetry technique. DESIGN:
      Prospective open label study. SETTINGS: Two multidisciplinary intensive care
      units. PATIENTS: Fifteen patients with norepinephrine-treated septic shock.
      INTERVENTIONS: Every patient with mean arterial pressure between 50 and 55 mmHg
      treated with high dose norepinephrine received an intravenous bolus dose of
      terlipressin as last resort therapy. A laser-Doppler probe and tonometer were
      introduced into the gastric lumen. MEASUREMENTS AND MAIN RESULTS: Terlipressin
      produced a decrease in cardiac output ( p<0.05), a progressive increase in mean
      arterial pressure ( p<0.05) and in GMP, detected by laser-Doppler flowmetry (
      p<0.05) over 30 min and sustained for at least 24 h. The ratio of GMP to systemic
      oxygen delivery increased after terlipressin bolus dose ( p<0.05). The gradient
      between gastric mucosal and arterial PCO(2) tended to be lower after
      terlipressin, and the difference was statistically significant ( p<0.05) after 8
      h. Terlipressin administration significantly increased ( p<0.05) urine output
      compared to baseline and higher values were found at each set of measurement. The
      terlipressin-induced increase in urine output was associated with a significantly
      increased creatinine clearance ( p<0.05). Reduction of the high-dose
      norepinephrine was observed in all patients ( p<0.05). CONCLUSIONS: Our findings
      showed that, in patients with norepinephrine-treated septic shock, terlipressin
      increased GMP, urine output and creatinine clearance by an increase in mean
      arterial pressure.

PMID- 14673521
TI  - A continuous quality-improvement program reduces nosocomial infection rates in
      the ICU.
AB  - OBJECTIVE: To assess the impact of a continuous quality-improvement program on
      nosocomial infection rates. DESIGN AND SETTING: Prospective single-center study
      in the medical-surgical ICU of a tertiary care center. PATIENTS. We admitted 1764
      patients during the 5-year study period (1995-2000); 55% were mechanically
      ventilated and 21% died. Mean SAPS II was 37+/-21 points and mean length of ICU
      stay was 9.7+/-16.1 days. INTERVENTIONS: Implementation of an infection control
      program based on international recommendations. The program was updated regularly
      according to infection and colonization rates and reports in the literature.
      MEASUREMENTS AND RESULTS: Prospective surveillance showed the following rates per
      1000 procedure days: ventilator-associated pneumonia (VAP) 8.7, urinary tract
      infection (UTI) 17.2, central venous catheter (CVC) colonization 6.1, and CVC
      related bacteremia and 2.0; arterial catheter colonization did not occur. In the
      5 years following implementation of the infection control program there was a
      significant decline in the rate per patient days of UTI, CVC colonization, and
      CVC-related bacteremia but not VAP. Between the first and second 2.5-year periods
      the time to infection increased significantly for UTI and CVC-related
      colonization. CONCLUSIONS: A continuous quality-improvement program based on
      surveillance of nosocomial infections in a nonselected medical-surgical ICU
      population was associated with sustained decreases in UTI and CVC-related
      infections.

PMID- 14673522
TI  - Disassociation of muscle triglyceride content and insulin sensitivity after
      exercise training in patients with Type 2 diabetes.
AB  - AIM/HYPOTHESIS: We determined the effect of exercise training on insulin
      sensitivity and muscle lipids (triglyceride [TG(m)] and long-chain fatty acyl CoA
      [LCACoA] concentration) in patients with Type 2 diabetes. METHODS: Seven patients
      with Type 2 diabetes and six healthy control subjects who were matched for age,
      BMI, % body fat and VO(2)peak participated in a 3 days per week training program
      for 8 weeks. Insulin sensitivity was determined pre- and post-training during a
      120 min euglycaemic-hyperinsulinaemic clamp and muscle biopsies were obtained
      before and after each clamp. Oxidative enzyme activities [citrate synthase (CS),
      beta-hydroxy-acyl-CoA (beta-HAD)] and TG(m) were determined from basal muscle
      samples pre- and post training, while total LCACoA content was measured in
      samples obtained before and after insulin-stimulation, pre- and post training.
      RESULTS: The training-induced increase in VO(2)peak (approximately 20%, p<0.01)
      was similar in both groups. Compared with control subjects, insulin sensitivity
      was lower in the diabetic patients before and after training (approximately 60%;
      p<0.05), but was increased to the same extent in both groups with training
      (approximately 30%; p<0.01). TG(m) was increased in patients with Type 2 diabetes
      (170%; p<0.05) before, but was normalized to levels observed in control subjects
      after training. Basal LCACoA content was similar between groups and was unaltered
      by training. Insulin-stimulation had no detectable effect on LCACoA content. CS
      and beta-HAD activity were increased to the same extent in both groups in
      response to training ( p<0.001). CONCLUSION/INTERPRETATION: We conclude that the
      enhanced insulin sensitivity observed after short-term exercise training was
      associated with a marked decrease in TG(m) content in patients with Type 2
      diabetes. However, despite the normalization of TG(m )to levels observed in
      healthy individuals, insulin resistance was not completely reversed in the
      diabetic patients.

PMID- 14673523
TI  - Stable transplantation results of magnetically retracted islets: a novel method.
AB  - AIMS/HYPOTHESIS: Large quantities of pure viable donor islets are necessary for
      clinical transplantation. At present, low yields and low viability of pancreatic
      islets after transplantation necessitate the use of multiple donors for a single
      recipient. In this study an improved method for obtaining large quantities of
      pure viable islets of Langerhans for transplantation was developed in the rat.
      METHODS: Islets of Langerhans were isolated from Albino Oxford rats. The donor
      pancreata were perfused in situ with iron oxide, which resulted in entrapment of
      iron particles in the capillaries of the islets. Subsequently, the islets were
      isolated by magnetic retraction. Islets obtained with this method were compared
      with islets obtained by density gradient-isolated islets with respect to yields,
      purity, and insulin production capacity. Islets isolated with the magnetic
      retraction method were transplanted under the renal capsule of streptozotocin
      induced diabetic recipients. Blood-glucose levels in the recipients were
      monitored for 2 months after transplantation. RESULTS: This method yielded more
      pure and viable islets than the conventional protocol. No contamination of
      exocrine tissue was observed after isolation. Furthermore, the islets isolated by
      magnetic retraction stained strongly positive for insulin during the entire
      observation period in vitro, and produced high amounts of insulin upon a
      challenge with glucose. The islets that were obtained by this new protocol were
      suitable for safe and effective transplantation. CONCLUSIONS/INTERPRETATION: We
      have shown that both the quantity and quality of islets obtained with this method
      were sufficient to induce insulin independence in a diabetic recipient using
      islets from only one donor.

PMID- 14673524
TI  - Reduction of diet-induced obesity in transgenic mice overexpressing uncoupling
      protein 3 in skeletal muscle.
AB  - AIMS/HYPOTHESIS: It has been suggested that uncoupling protein 3 (UCP3) can
      increase energy expenditure, thereby regulating body weight. Although studies on
      UCP3 knock-out mice suggest that lack of UCP3 function does not cause obesity or
      Type 2 diabetes, it is possible that up-regulation of UCP3 function improves
      these disorders or their clinical sequelae. A 10- to 20-fold increase of UCP3
      gene expression is achievable through physiological or pharmacological stimuli.
      We examined the phenotype of transgenic mice with approximately 18-fold
      overexpression of mouse UCP3 mRNA in skeletal muscle. METHODS: We generated
      transgenic mice with approximately 18-fold overexpression of mouse UCP3 mRNA in
      skeletal muscle under control of the skeletal muscle-specific muscle creatine
      kinase gene promoter. The phenotype of these mice was analysed either on a
      standard diet or on a 4-week high-fat diet. RESULTS: In mice on standard chow,
      there was no difference in body weight, oxygen consumption and mitochondrial
      protonmotive force between transgenic mice and non-transgenic littermates.
      However, transgenic mice tended to have lower body weight, increased oxygen
      consumption and decreased mitochondrial protonmotive force than the control mice.
      Transgenic mice on a 4-week high-fat diet consumed much more oxygen and had
      noticeably less weight gain and less epididymal fat, as well as better glucose
      tolerance than non-transgenic littermates. CONCLUSIONS/INTERPRETATION: Our study
      shows that 18-fold overexpression of UCP3 mRNA in the skeletal muscle reduced
      diet-induced obesity. An 18-fold increase of UCP3 mRNA can be attained by
      physiological or pharmacological stimuli, suggesting that UCP3 has therapeutic
      potential in the treatment of obesity.

PMID- 14673528
TI  - CC chemokine receptor 5 delta32 polymorphism in two independent cohorts of
      hepatitis C virus infected patients without hemophilia.
AB  - Recently CC chemokine receptor 5 (CCR5) related immune mechanisms and a
      functional mutation of the CCR5 gene have been implicated in hepatitis C virus
      (HCV) infection in a cohort of predominantly hemophiliac patients. The present
      study investigated the frequency and clinical consequences of the CCR5 Delta32
      mutation in two genetically homogeneous populations of HCV infected patients with
      a different risk profile for infection. Genomic DNA samples from 333 German
      patients with chronic HCV infection were screened by PCR for the presence of the
      CCR5 Delta32 polymorphism. In-hospital patients admitted for other diseases than
      viral hepatitis but with a comparable risk for HCV exposure were used as control
      population ( n=125). Allele frequencies of CCR5 Delta32 polymorphism did not
      differ significantly between the two groups (7.6% and 9.5%, respectively) and
      control subjects (10.4%), and did not deviate from Hardy-Weinberg equilibrium in
      any group. Furthermore, there were no major differences between patients with
      respect to HCV genotypes, viral loads, liver enzymes, or fibrosis scores in
      relation to the presence or absence of the heterozygous CCR5 Delta32 mutation.
      Differences in inflammatory scores in liver biopsy samples and response to
      antiviral therapy in CCR5 Delta32 heterozygotes in one cohort could neither be
      reproduced in the other group of patients nor when both cohorts were pooled.
      These results argue against a strong effect of the CCR5 Delta32 deletion
      regarding these phenotypes. In conclusion, we found no increased frequency of the
      CCR5 Delta32 polymorphism in two independent cohorts of patients with HCV
      infection but without hemophilia as the main risk factor for infection. As the
      major difference to investigations demonstrating an association between CCR5
      Delta32 and HCV infection is the selection of cases and controls, our study
      emphasizes the importance of epidemiological criteria for association studies of
      HCV infection.

PMID- 14673527
TI  - Therapeutics for Duchenne muscular dystrophy: current approaches and future
      directions.
AB  - Duchenne muscular dystrophy (DMD) is the most common X-linked neuromuscular
      disorder. The devastating nature of DMD has led to an intense effort toward
      finding a cure for this disease, dating back to the time when Duchenne first
      initiated clinical trials using faradic stimulation for DMD patients.
      Unfortunately despite the passage of some 150 years the disease remains
      incurable, and its medical management is largely supportive. However, the
      discovery of the DMD gene about 20 years ago has allowed a change in the focus of
      therapeutic strategy dramatically toward delivery of the missing gene/protein.
      Indeed, some degree of success has been achieved in preclinical animal studies
      using such strategies, and gene therapy trials are currently underway in humans.
      Pharmacological approaches for DMD are also being developed since they can
      circumvent some of the technical problems associated with gene and cell based
      therapy. This review explores developments in therapeutic approaches for DMD.

PMID- 14673530
TI  - A very phoxy business.

PMID- 14673529
TI  - Dichotomy between Lactobacillus rhamnosus and Klebsiella pneumoniae on dendritic
      cell phenotype and function.
AB  - The reaction of the intestinal immune system to intestinal bacteria shows
      striking differences between various bacterial strains. Whereas Klebsiella
      pneumoniae induces a fierce proinflammatory reaction, the probiotic strain
      Lactobacillus rhamnosus has clear anti-inflammatory effect in gastrointestinal
      disease and allergy. The molecular basis for this dichotomy is poorly understood
      but is likely to involve different modulation of antigen-presenting dendritic
      cells (DC) by L. rhamnosus and K. pneumoniae. Hence we evaluated phenotypic and
      functional characteristics of DC matured in the presence of L. rhamnosus and K.
      pneumoniae. Monocyte-derived immature DC were cultured in the presence of live
      bacteria to obtain mature DC. Both micro-organisms induced maturation of immature
      DC as shown by CD83 and CD86 expression, but receptors involved in activation of
      Th1 cells were expressed predominantly on DC exposed to K. pneumoniae. In
      contrast to K. pneumoniae, maturation with L. rhamnosus resulted in lower TNF
      alpha, IL-6, and IL-8 production by immature DC and lower IL-12 and IL-18
      production by mature DC. Moreover, L. rhamnosus led to the development of T cells
      without a typical Th phenotype whereas K. pneumoniae induced a Th1 immune
      response, dependent mainly on IL-12 production. Thus our results strongly support
      the concept that differential modulation of DC explains the differences in the
      immune response to various bacterial strains and indicates that K. pneumoniae
      induces Th1 immune responses via DC.

PMID- 14673531
TI  - [Acute limb ischemia from the general surgeon's point of view. How much knowledge
      of vascular surgery is necessary?].
AB  - The diagnosis of acute peripheral ischemia can be obtained based on clinical
      presentation, inspection, and palpation of the affected extremity. Unfractionated
      heparin as a single shot is immediately given followed by continuous infusion
      when diagnosis is clinically evident and contraindications are excluded.
      Thromboembolectomy using a Fogarty catheter is immediately performed in patients
      with evidence of arterial embolization and signs of advanced ischemia (TASC
      IIb/III) followed by intraoperative angiography. Patients with evidence of
      arterial thrombosis require urgent angiography followed by thrombectomy and
      probably subsequent endovascular or surgical interventions and vascular
      reconstruction. For patients with moderate ischemia (TASC IIa), initial
      diagnostic angiography is recommended followed by primary thrombectomy with
      subsequent intraoperative angiography and immediate endovascular or operative
      treatment of remaining vascular problems. As an alternative therapeutic option
      initial catheter-guided local thrombolysis can be performed in selected patients
      with the intention of subsequent limb revascularization or unmasking relevant
      vessel alterations leading to specific endovascular or surgically performed
      vascular reconstruction. Possible development of muscle ischemia because of
      increased compartment pressure should be considered and fasciotomy performed when
      indicated. Primary amputation of the severely ischemic limb after initial
      thrombectomy might be recommended in patients with life-threatening organ failure
      related to muscle necrosis.

PMID- 14673532
TI  - [Intra-arterial lysis therapy in acute limb ischemia. Technical possibilities and
      limits of indication].
AB  - Acute limb ischemia is associated with a high risk of death and loss of the
      extremity. To restore the blood flow, several percutaneous thrombolytic
      techniques were developed. To achieve a targeted thrombus infiltration, the
      continuous application of low-dose urokinase or recombinant tissue plasminogen
      activator using a specific lysis catheter with sideholes is preferable.
      Concerning the amputation-free survival, thrombolysis is superior to surgery for
      occlusions of native vessels or bypass grafts that are not older than 2 weeks.
      Furthermore, the percutaneous approach permits the simultaneous treatment of the
      underlying lesion by angioplasty or stent implantation after dissolution of the
      occluding thrombus. The higher risk of complications must be balanced against
      risks of surgery in each patient.

PMID- 14673533
TI  - [Radiological diagnosis and treatment of acute limb ischemia].
AB  - Acute limb ischemia is associated with significant morbidity and mortality,
      despite diagnostic and therapeutic advances. Threatened limbs require immediate
      imaging in order to determine the subsequent therapeutic procedures. Conventional
      angiography in the DSA technique still has advantages over CT and MR angiography.
      In acute arterial occlusions below the femoral bifurcation, endovascular
      treatment with intra-arterial local thrombolysis or percutaneous thrombectomy is
      an alternative to open vascular surgical procedures. The following article
      describes diagnostic and therapeutic strategies for acute limb threat induced by
      arterial occlusion.

PMID- 14673535
TI  - [Surgical management of abdominal aortic aneurysms with coexistent intestinal
      disease].
AB  - The management of patients suffering from abdominal aortic aneurysms with
      concomitant intestinal disease is demanding. Surgical procedures have to be
      evaluated meticulously with regard to morbidity and priority. We retrospectively
      investigated early and late results of nine patients (eight males, one female)
      with coincidental aortic and intestinal surgery during the last 9.5 years. The
      average age was 77 years (range 67-85). One-stage procedures were undertaken
      twice with implantation of aortic grafts to replace abdominal aortic aneurysms
      (AAA). During these emergency procedures, an aortoduodenal fistula was repaired
      in one case and resection of an ischemic segment of the sigmoid colon was
      resected in another. Seven two-stage procedures were performed as elective
      surgery. Five AAA were excluded before the intestinal repair. In two cases of
      urgent visceral pathologies, colon resection was done first, followed by
      elimination of the AAA. In case of elective surgery, two-stage procedures seem to
      be safe and effective. However, in certain emergent cases, one-stage procedures
      with implantation of vascular grafts in combination with colon or bowel surgery
      might also be justified.

PMID- 14673534
TI  - [Clinical pathways -- intervention or surgery for acute ischemia of the
      extremities].
AB  - There is still controversial discussion concerning the therapy of limb
      threatening ischaemia. In a retrospective study, we investigated and compared
      surgical and percutaneous interventional methods in the treatment of both embolic
      and thrombotic vascular occlusions in patients with pre-existing arteriosclerotic
      disease and attempted to propose therapy guidelines for these methods in the
      therapy of acute limb ischaemia. Percutaneous mechanical thrombectomy represents
      a viable therapeutic alternative to surgical or surgical-interventional
      modalities, particularly in patients with occlusions consisting of soft, embolic
      material or located in infrapopliteal vessels. The indication for each respective
      method should be interdisciplinary and must be based on the individual patients'
      clinical and angiographic findings. Additional intraoperative endovascular
      procedures increase the range of therapeutic options and permit optimal
      revascularisation of vessels both proximal and distal to the site of occlusion.

PMID- 14673536
TI  - [Prospective comparative observational study on the antibiotic treatment of
      secondary peritonitis in Germany -- efficacy and cost analysis].
AB  - AIMS: Cephalosporins and broad-spectrum penicillins in combination with
      metronidazole are suitable for treatment of secondary peritonitis. The aim of
      this study was to compare the clinical and bacteriological efficacy, length of
      hospital stay (LOS), treatment costs of ceftriaxone (CRO) in combination with
      metronidazole vs standard regimens (SR) 1 and 2. METHODS: Patient data were
      subjected to matched-pairs analysis according to four different categories of the
      Mannheim peritonitis index. RESULTS. From January 1998 to March 2000, a total of
      365 patients from 59 surgical wards in German hospitals were included. Clinical
      efficacy was 90.2% vs 70.4% ( P=0.004) for CRO/SR 1 and 78.3% vs 82.6% for CRO/SR
      2. Bacteriological efficacy was comparable. Antibiotic treatment costs were
      593/539 Euros for CRO/SR 1 and 466/750 Euros for CRO/SR 2, i.e., costs for CRO
      were 37.9% lower than with SR 2. CONCLUSION: Based on clinical, bacteriological,
      and pharmacoeconomic results, ceftriaxone in combination with metronidazole can
      be regarded as a first-line antimicrobial treatment of secondary peritonitis.

PMID- 14673537
TI  - [TAPP versus TEP: a retrospective analysis 5 years after laparoscopic
      transperitoneal and total endoscopic extraperitoneal repair in inguinal and
      femoral hernia].
AB  - INTRODUCTION: The 5-year results after laparoscopic repair of inguinal and
      femoral hernias with the TAPP and TEP techniques were analyzed. METHODS: We
      examined all patients after inguinal repair with the TAPP or TEP technique for
      the treatment of inguinal and/or femoral hernias from September 1992 to February
      1996 performed by four surgeons at the Luneburg community hospital (TAPP: 294
      patients with 352 hernias, TEP: 278 patients with 324 hernias). The follow-up
      included a clinical examination, a questionnaire, and an ultrasound examination
      of the inguinal area. RESULTS: The follow-up rate was 93.5% after TAPP and 91%
      after TEP with a median follow-up of 5.7 postoperative years. With a total
      complication rate of almost 10.2% both methods did not differ. The recurrence
      rate after TAPP was 2.3% ( re-recurrence rate 6.7%) and 1.5% after TEP ( re
      recurrence rate 4.8%). Recurrences occurred on average 45 months after TAPP and
      36.6 months after TEP. CONCLUSION: TAPP and TEP are both safe and efficient.
      Because of the late occurrence of recurrence we suggest randomized prospective
      studies over a period of 5-10 postoperative years.

PMID- 14673538
TI  - [Clinical pathways: effective and efficient inpatient treatment].
AB  - The new hospital funding system based on a diagnosis-related group (DRG) system
      and the economic competition involved require large-scale changes in hospital
      structures and processes. Clinical pathways are multidisciplinary plans of best
      clinical practice for specified groups of patients with a particular diagnosis
      that aid the coordination and delivery of high quality care. The clinical pathway
      originally used in the USA and Australia was aimed at shortening the hospital
      stay and reducing healthcare costs, which has become an increasingly important
      issue in medicine. Furthermore, it is an appropriate tool to standardize medical
      care and increase patient satisfaction. Clinical pathways are able to standardize
      care for patients with a similar diagnosis, procedure, or symptom. There are four
      essential components of a clinical pathway: a timeline, the categories of care or
      activities and their interventions, intermediate- and long-term outcome criteria,
      and the variance record. In contrast to practice guidelines, protocols, and
      algorithms, clinical pathways are utilized by a multidisciplinary team and focus
      on quality and coordination of care.

PMID- 14673539
TI  - [From clinical guidelines to clinical pathways: development of a management
      oriented algorithm for the treatment of polytraumatized patients in the acute
      period].
AB  - INTRODUCTION: The treatment of polytraumatized patients in the acute period is an
      exemplary model of multidisciplinary cooperation in a very critical timeframe.
      Implementing standards formulated in the clinical guidelines of the German
      Association of Traumatology requires a detailed description of "how to do it."
      METHODS: Based on the guidelines and validated quality indictors, the optimal
      standard of care as the goal was defined. A clinical algorithm was developed and
      personal responsibilities and time limits were clearly assigned to each decision
      step and action. Checklists, documentation charts, and a full text supplement the
      algorithm. The complete pathway was adopted by representatives of all
      occupational groups involved in early trauma care in a consensus process.
      RESULTS: Improvement potentials were identified in those areas for which the
      guidelines did not provide explicit recommendations. These represent the key
      elements of the algorithm. Pathway-specific review criteria (quality indicators)
      were defined for scheduled reevaluation. CONCLUSIONS: Implementing clinical
      guidelines at the local level requires a problem-oriented and management-oriented
      elaboration towards a clinical pathway as the basis for a quantitative process
      and cost analysis.

PMID- 14673540
TI  - [Rupture of internal iliac artery aneurysm -- a rare cause of life-threatening
      rectal bleeding].
AB  - Isolated aneurysms of the iliac arteries are rare. Located deep in the lesser
      pelvis, they are diagnosed late or in a symptomatic stage. Because of their
      manifold anatomic relationships to pelvic structures, iliac aneurysms may cause
      different symptoms such as obstipation, hydronephrosis, venous thrombosis, and
      entrapment neuropathy. Aneurysm rupture is associated with high mortality. The
      rupture of an iliac aneurysm into the rectum with massive lower intestinal
      bleeding is extremely rare. We report a patient with 6-year follow-up after
      aneurysm resection, extra-anatomic bypass, and suture repair of the rectum with
      temporary colostomy.

PMID- 14673542
TI  - Difficulties in removing ACE tibial intramedullary nail.
AB  - We experienced three cases of refracture and two cases of failure to remove the
      nail while trying to take out ACE tibial nails from healed tibial fractures. In
      order to determine the risk factors associated with difficulties in nail removal,
      these five patients were compared in the parameters of age, gender, duration of
      nail in situ, nail diameter, nail length, and level of fracture with 30 patients
      who had uneventful removal. Younger age of the patient was significantly
      associated with the difficulty in nail removal.

PMID- 14673541
TI  - [Accessory spleen in the pancreatic tail -- a neglected entity? A contribution to
      embryology, topography and pathology of ectopic splenic tissue].
AB  - According to autoptic studies, accessory spleens may be found in 10% to 15% of
      the population, in 1% to 2% they are located in the pancreatic tail. They thus
      have to be taken into account in the differential diagnosis of intra- and
      peripancreatic tumorous lesions. After splenorenal fusion, they can be found
      pararenally and retroperitoneally, and after splenogonadal fusion they can
      descend into the pelvis or scrotum. Since they usually are asymptomatic, they are
      mostly discovered accidentally. The diagnosis is ascertained by a scintigram with
      technetium-99-marked, heat-damaged red blood cells. If resection is necessary,
      the organ adherent to the encapsulated accessory spleen should be preserved. By
      means of three case reports (intrapancreatic accessory spleen, retroperitoneal
      accessory spleen and torsion-infarcted wandering spleen), the surgical relevance
      of ectopic splenic tissue is discussed.

PMID- 14673543
TI  - Sodium bicarbonate-augmented stress thallium myocardial scintigraphy.
AB  - It is well known that sodium bicarbonate in pharmacological doses induces
      transient alkalosis, causing intracellular transport of serum potassium. The aims
      of this study were (a) to investigate whether, in humans, myocardial thallium-201
      uptake can be augmented by pretreatment with a single bolus of sodium bicarbonate
      at a pharmacological dose, (b) to verify general safety aspects of the
      intervention and (c) to evaluate the clinical implications of augmentation of
      (201)Tl uptake, if any. Routine exercise myocardial scintigraphy was performed
      twice in eight adult volunteers (five normal and three abnormal), once without
      intervention and the second time (within a week) following intravenous
      administration of sodium bicarbonate (88 mEq in 50 ml) as a slow bolus 1 h prior
      to the injection of (201)Tl. Conventional myocardial thallium study was compared
      with sodium bicarbonate interventional myocardial scintigraphy with respect to
      myocardial uptake (counts per minute per mCi injected dose), washout patterns in
      normal and abnormal myocardial segments, and overall clinical interpretation
      based on planar and single-photon emission tomographic (SPET) images. All
      patients remained asymptomatic after the intervention. A mean increase of 53% in
      myocardial uptake of thallium was noted in post-exercise acquisitions after the
      intervention, confirming uptake of the tracer via the potassium-hydrogen pump and
      its augmentation by transient alkalosis. The washout pattern remained unchanged.
      The visual quality of planar and SPET images improved significantly after the
      intervention. Out of the five abnormal myocardial segments identified in three
      cases, four showed significant filling-in after the intervention, causing the
      diagnosis to be upgraded from "partial scar" to "ischaemia", or from "ischaemia"
      to "normal". The overall scan impression changed in two out of three such cases.
      Sodium bicarbonate augmentation may have significant implications for stress
      thallium scintigraphy and may be a new parameter for defining myocardial
      viability.

PMID- 14673544
TI  - Cloning of the pelA gene from Bacillus licheniformis 14A and biochemical
      characterization of recombinant, thermostable, high-alkaline pectate lyase.
AB  - The pectate lyase gene pelA from alkaliphilic Bacillus licheniformis strain 14A
      was cloned and sequenced. The nucleotide sequence corresponded to an open reading
      frame of 1,026 bp that codes for a 39 amino acid signal peptide and a mature
      protein with a molecular mass of 33,451 Da. The mature PelA showed significant
      homology to other pectate lyases belonging to polysaccharide lyase family 1, such
      as enzymes from different Bacillus spp. and Erwinia chrysanthemi. The pelA gene
      was expressed in Escherichia coli as a recombinant fusion protein containing a C
      terminal His-tag, allowing purification to near homogeneity in a one-step
      procedure. The values for the kinetic parameters K(m) and Vmax of the fusion
      protein were 0.56 g/l and 51 micromol/min, respectively. The activity of purified
      PelAHis was inhibited in the presence of excess substrate. Characterization of
      product formation revealed unsaturated trigalacturonate as the main product. The
      yields of unsaturated trigalacturonic acids were further examined for the
      substrates polygalacturonic acid, citrus pectin and sugar-beet pectin.

PMID- 14673545
TI  - Purification and characterization of an N-acetylglucosaminidase produced by a
      Trichoderma harzianum strain which controls Crinipellis perniciosa.
AB  - Isolate 1051 of Trichoderma harzianum, a mycoparasitic fungus, was found to
      impair development of the phytopathogen, Crinipellis perniciosa, in the field.
      This Trichoderma strain growing in liquid medium containing chitin produced
      substantial amounts of chitinases. The N-acetylglucosaminidase present in the
      culture-supernatant was purified to homogeneity by gel filtration and hydrophobic
      interaction chromatography, as demonstrated by SDS-PAGE analysis. The enzyme had
      a molecular mass of 36 kDa and hydrolyzed the synthetic substrate rho-nitrophenyl
      N-acetylglucosaminide (rhoNGlcNAc) with Michaelis-Menten kinetics. Maximal
      activities were determined at pH 4.0 and a temperature range of 50-60 degrees C.
      Km and Vmax values for rhoNGlcNAc hydrolysis were 8.06 micromoles ml(-1) and 3.36
      micromoles ml(-1) min(-1), respectively, at pH 6.0 and 37 degrees C. The enzyme
      was very sensitive to Fe3+, Mn2+ and Co2+ ions, but less sensitive to Zn2+, Al3+,
      Cu2+ and Ca2+. Glucose at a final concentration of 1 mM inhibited 65% of the
      original activity of the purified enzyme. Determination of the product (reducing
      sugar) of hydrolysis of C. perniciosa mycelium and scanning electron microscopic
      analysis revealed that the N-acetylglucosaminidase hydrolyses the C. perniciosa
      cell wall.

PMID- 14673546
TI  - The effect of pfl gene knockout on the metabolism for optically pure D-lactate
      production by Escherichia coli.
AB  - The effect of gene knockout on metabolism in the pflA-, pflB-, pflC-, and pflD-
      mutants of Escherichia coli was investigated. Batch cultivations of the pfl-
      mutants and their parent strain were conducted using glucose as a carbon source.
      It was found that pflA- and pflB- mutants, but not pflC- and pflD- mutants,
      produced large amounts of D-lactate from glucose under the microaerobic
      condition, and the maximum yield was 73%. In order to investigate the metabolic
      regulation mechanism, we measured enzyme activities for the following eight
      enzymes: glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase,
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH), pyruvate kinase, lactate
      dehydrogenase (LDH), phosphoenolpyruvate carboxylase, acetate kinase, and alcohol
      dehydrogenase. Intracellular metabolite concentrations of glucose 6-phosphate,
      fructose 1,6-bisphosphate, phosphoenolpyruvate, pyruvate, acetyl coenzyme A as
      well as ATP, ADP, AMP, NADH, and NAD+ were also measured. It was shown that the
      GAPDH and LDH activities were considerably higher in pflA- and pflB- mutants,
      which implies coupling between NADH production and consumption between the two
      corresponding reactions. The urgent energy requirement was shown by the lower
      ATP/AMP level due to both oxygen limitation and pfl gene knockout, which promoted
      significant stepping-up of glycolysis when using glucose as a carbon source. It
      was shown that the demand for energy is more important than intracellular redox
      balance, thus excess NADH produced through GAPDH resulted in a significantly
      higher intracellular NADH/NAD+ ratio in pfl- mutants. Consequently, the
      homolactate production was achieved to meet the requirements of the redox balance
      and the energy production through glycolysis. The effect of using different
      carbon sources such as gluconate, pyruvate, fructose, and glycerol was
      investigated.

PMID- 14673547
TI  - Lactulose production by beta-galactosidase in permeabilized cells of
      Kluyveromyces lactis.
AB  - Lactulose production from lactose and fructose was investigated with several
      commercial beta-galactosidases. The enzyme from Kluyveromyces lactis exhibited
      the highest lactulose productivity among the beta-galactosidases tested. The
      reaction conditions for lactulose production were optimized using cells that had
      been permeabilized by treatment with 50% (v/v) ethanol: cell concentration, 10.4
      g l(-1); concentration of substrates, 40% (w/v) lactose and 20% (w/v) fructose;
      temperature, 60( degrees )C; pH 7.0. Under these conditions, the permeabilized
      cells produced approximately 20 g l(-1) lactulose in 3 h with a lactulose
      productivity of 6.8 g l(-1) h(-1). These results represent 1.3- and 2.1-fold
      increases in lactulose concentration and productivity compared with untreated
      washed cells. This is the first reported trial of enzymatic synthesis of
      lactulose using permeabilized yeast cells.

PMID- 14673548
TI  - Knowledge of the Bacillus subtilis genome: impacts on fundamental science and
      biotechnology.
AB  - The advent of genomics has greatly influenced fundamental and applied
      microbiology. This has become paradigmatic in the case of Bacillus subtilis, a
      primary model bacterium for research and biotechnology. Indeed, mining its genome
      has provided more fruitful information than classical approaches would have
      yielded in a longer period of time. Through advanced analysis of its genome and
      transcriptome, fundamental discoveries dealing with the informational
      architecture of the B. subtilis chromosome, as well as with the elucidation of
      its pathway-level regulation of gene expression, have been achieved. The
      possibility of performing a complete metabolic manipulation of the secretory
      pathway of Bacillus is promising important biotechnological fallouts. Similar
      emphasis exists for the possibility of controlling the cell in the formation of
      biofilms with specific physical and chemical characteristics. At the theoretical
      level, the new concept of genetic superinformation has been formulated and its
      analytical approach implemented, while the understanding of the minimal genetic
      requirements for the existence of a reproducing bacterial cell is being tackled.
      In summary, the impact of the B. subtilis genome has philosophically
      revolutionised the way that basic knowledge is translated into applied
      microbiology and biotechnology, making this bacterium the workhorse of post
      genomic microbiology.

PMID- 14673549
TI  - Nucleotide sequencing analysis of the swine 433-kb genomic segment located
      between the non-classical and classical SLA class I gene clusters.
AB  - Genome analysis of the swine leukocyte antigen ( SLA) region is needed to obtain
      information on the MHC genomic sequence similarities and differences between the
      swine and human, given the possible use of swine organs for xenotransplantation.
      Here, the genomic sequences of a 433-kb segment located between the non-classical
      and classical SLA class I gene clusters were determined and analyzed for gene
      organization and contents of repetitive sequences. The genomic organization and
      diversity of this swine non-class I gene region was compared with the orthologous
      region of the human leukocyte antigen ( HLA) complex. The length of the fully
      sequenced SLA genomic segment was 433 kb compared with 595 kb in the
      corresponding HLA class I region. This 162-kb difference in size between the
      swine and human genomic segments can be explained by indel activity, and the
      greater variety and density of repetitive sequences within the human MHC. Twenty
      one swine genes with strong sequence similarity to the corresponding human genes
      were identified, with the gene order from the centromere to telomere of HCR -
      SPR1 - SEEK1 - CDSN - STG - DPCR1 - KIAA1885 - TFIIH - DDR - IER3 - FLOT1 - TUBB 
      KIAA0170 - NRM - KIAA1949 - DDX16 - FLJ13158 - MRPS18B - FB19 - ABCFI - CAT56.
      The human SEEK1 and DPCR1 genes are pseudogenes in swine. We conclude that the
      swine non-class I gene region that we have sequenced is highly conserved and
      therefore homologous to the corresponding region located between the HLA-C and
      HLA-E genes in the human.

PMID- 14673550
TI  - Independent expression of the two paralogous CCL4 genes in monocytes and B
      lymphocytes.
AB  - The CCL4 chemokine is secreted by a variety of cells following stimulation. CCL4
      affects several different types of cells that are important for acute
      inflammatory responses and are critical for the development of specific immune
      responses to foreign antigens. The human genome contains two genes for the CCL4
      chemokine. Although highly homologous, the two genes encode slightly different
      proteins. We analyzed the mRNA expressed in monocytes and B lymphocytes and found
      that while monocytes express predominantly one CCL4 gene, known as ACT-2,
      peripheral blood B lymphocytes express a mixture of ACT-2 and the second CCL4
      gene, lymphocyte activating gene-1 ( LAG-1). Although peripheral blood B cells,
      CD27(-) B cells, and CD27(+) B cells all express a mixture of LAG-1 and ACT-2,
      the B-cell lines that were studied regulate the two genes independently. RL, SU
      DHL-6, and REH cells predominantly express LAG-1. These studies demonstrate that
      monocytes and B cells utilize different mechanisms to regulate expression of the
      two CCL4 genes and suggest that the two genes may not have identical activities.

PMID- 14673551
TI  - MR imaging of soft tissue tumors and tumor-like lesions.
AB  - The evaluation of a soft tissue mass in a child should proceed with a
      differential diagnosis in mind, based on the clinical history, age of the child,
      and location of the abnormality. Small, superficial masses can be initially
      evaluated with sonography. More extensive or deep lesions usually require cross
      sectional imaging. With the exception of myositis ossificans, magnetic resonance
      (MR) imaging has largely replaced the use of computed tomography. MR imaging is
      used to delineate the extent of a lesion, to evaluate response to therapy, and to
      monitor postoperative complications. There is great overlap in the MR imaging
      characteristics of benign and malignant lesions, making tissue sampling
      imperative for diagnosis.

PMID- 14673552
TI  - Revascularization of the testis using a vascular induction technique: a potential
      approach for staged orchiopexy in high-undescended testis.
AB  - The present study was designed to determine whether a fasciovascular flap as a
      vascular carrier could be used to revascularize the undescended testis for
      avoiding the hazardous effects of the Fowler-Stephens procedure, high division of
      the spermatic vessels, and for bringing high-undescended testes into the scrotum.
      A total of 25 Wistar rats were divided into five groups of five rats each. In
      each group, surgical procedures were performed bilaterally, i.e. ten testes in
      each group, as follows: sham-operated controls (group 1), undescended testes
      (group 2), high division of the spermatic vessels (group 3), vascular induction
      with immediate division of spermatic vessels (group 4), and with delayed division
      of spermatic vessels (group 5). Evaluations were done by measuring the testicular
      weight and volume, testicular blood flow, and testicular biopsy scores and by
      microangiography. A moderate to severe decrease in testicular weight and volume
      in all experimental groups was observed compared with the sham-operated controls
      (group 1), but this was significantly less in groups 2 and 5. High division of
      the spermatic vessels in groups 3 and 4 resulted in a significantly greater
      decrease in the testicular blood flow, but this did not occur in group 5.
      Microangiographically, an impaired vascular supply from the deferential artery in
      group 3 and insufficient revascularization from the fasciovascular carrier in
      group 4 were observed. However, efficient revascularization stemming from the
      superficial epigastric artery of the fasciovascular flap was found in group 5.
      The testicular biopsy scores of groups 2 and 5 were significantly greater than
      those of groups 3 and 4. The results of the present study demonstrate that the
      fasciovascular flap as a vascular carrier revascularizes the testis through
      spermatic vessels after delayed division and provides an adjuvant treatment
      modality or first-stage procedure in a salvage operation for high-undescended
      testis during staged orchiopexy.

PMID- 14673554
TI  - Comparison of conventional and diffusion-weighted MRI and proton MR spectroscopy
      in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke
      like events.
AB  - The mechanism of neurological disturbances in patients with mitochondrial
      myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is
      controversial. We studied 12 patients with MELAS using conventional and diffusion
      weighted MRI (DWI) and MR spectroscopy (MRS), to look at the physiopathology of
      the stroke-like events. Although conventional MRI showed lesions in all patients,
      DWI was more sensitive. One patient did not show high signal on DWI 48 h after a
      from stroke-like episode, but MRS demonstrated a lactate peak in left occipital
      lobe; 2 weeks after the attack, high signal was demonstrated on the right frontal
      lobe where MRS had shown a lactate peak. Our findings suggest a possible
      predictive ability of (1)H-MRS, in showing early MELAS lesions and supports the
      hypothesis that mitochondrial metabolic dysfunction may precedes abnormalities on
      DWI.

PMID- 14673553
TI  - Perfusion-weighted MRI as a marker of response to treatment in acute and subacute
      stroke.
AB  - We carried out baseline and short-term follow-up MRI, including perfusion
      weighted imaging (PWI) and tests of neurologic and cognitive function on 15
      consecutive patients with large-vessel ischemic stroke who showed a persistent
      large perfusion-diffusion mismatch at enrollment up to seven days after the onset
      of symptoms. Of these, ten underwent induced blood pressure elevation with
      phenylephrine and oral medications (in eight) or intravenous fluids (in two) with
      the goal of improving perfusion; five had no such treatment. Significant
      functional improvement was defined by a reduction of 3 or more points on the NIH
      stroke scale (NIHSS). Significant improvement in perfusion was defined by a
      reduction in the volume of hypoperfused brain by 30 cc on PWI using time-to-peak
      (TTP) maps, without enlargement of the infarct. There was a strong, statistically
      significant association between improved function and improved perfusion: six
      (75%) of eight patients who improved in function, but none of the seven who did
      not, showed a reduction in volume of hypoperfused brain. All six patients who met
      the perfusion goal, and only two (22%) of nine who did not showed significant
      functional improvement (Fisher's exact: P < 0.01). There were no differences
      between patients who improved functionally and those who did not with respect to
      age, initial volume of abnormality on DWI or PWI, initial NIHSS, or changes on
      DWI. These findings indicate that reduction in volume of hypoperfused brain on
      PWI is a marker of response to treatment to improve perfusion even in subacute
      stroke and that partial reperfusion of regions of salvageable but dysfunctional
      tissue is a mechanism of improved function associated with induced blood pressure
      elevation.

PMID- 14673555
TI  - Pharmacokinetic modelling of valproic acid from routine clinical data in Egyptian
      epileptic patients.
AB  - OBJECTIVE: This paper describes a developed pharmacokinetic model for the
      estimation of valproic acid (VPA) clearance (CL) calculated from routine clinical
      data taken from Egyptian epileptic patients. METHODS: Retrospective clinical data
      from 81 adult and paediatric epileptic patients with one trough VPA serum
      concentration per patient were analysed using NONMEM to estimate drug CL and
      determine the influence of different covariates. A qualification group of 20
      epileptic children (3-13 years old) was used to evaluate the final model.
      RESULTS: The population CL as estimated by base model (no covariates) was 0.581 l
      h(-1) with inter-individual variability (C.V. %) of 17.4% and SD of residual
      error was 6.82 mg l(-1). Univariate selection and backward deletion of different
      covariates led to the development of the final regression model of CL as follows:
      CL(Lh-1) = 0.101 + 0.151 * CBZ + 0.000248 * VPADD + 0.0968 * age/20 + 0.0803 *
      INDI, in which CBZ indicates co-administration of carbamazepine, VPADD the daily
      dose of VPA and INDI uncontrolled epilepsy. The between-subject variability in CL
      was 23.6% while the standard deviation of the residual error was 5.24 mg l(-1).
      The model predictions in the qualification group were found to have no bias and
      satisfactory precision. CONCLUSION: The population pharmacokinetic model for VPA
      could be used for a priori recommendation and dose optimisation of that drug in
      the Egyptian population of epileptic patients.

PMID- 14673556
TI  - At what stage of manual visual reaction time does interhemispheric transmission
      occur: controlled or ballistic?
AB  - Interhemispheric transfer (IT) time through the corpus callosum can be measured
      with a manual reaction time (RT) to lateralized visual stimuli (the so-called
      Poffenberger paradigm) by subtracting mean RT of faster uncrossed hemifield-hand
      combinations (not requiring an IT) from slower crossed combinations (requiring an
      IT). That the corpus callosum is involved in IT has been demonstrated by its
      dramatic lengthening in patients with a section of the corpus callosum. However,
      it is still unclear whether the signal transmitted by the corpus callosum
      concerns perceptual or motor stages of RT. To try and cast light on this
      question, in a first experiment we tested normal subjects on a partially modified
      Poffenberger paradigm with stop trials intermingled with go trials. In the
      former, subjects are supposed to refrain from responding following a stop signal
      (stop-signal paradigm). This paradigm can tease apart the contribution of the
      controlled and ballistic stages to overall RT and, used together with the
      Poffenberger task, enables one to assess the stage at which IT occurs. The
      controlled stage lies before the point of no return, i.e. the point beyond which
      the response cannot be inhibited, and concerns perceptual and pre-motor
      processes, while the ballistic stage occurs after the point of no return and
      concerns the motoric aspect of the response. We found that the slower responses
      typically obtained in the crossed conditions were more likely to be inhibited
      than the faster uncrossed responses and this suggests that IT occurs prior to the
      point of no return. Since the precise locus of the point of no return is
      uncertain, in a second experiment we used response force as a dependent variable
      reflecting the activation of the motor cortex. We found that none of the force
      parameters studied differed between crossed and uncrossed conditions while the
      temporal parameters confirmed the presence of an advantage of the uncrossed
      combinations. Altogether these results suggest that callosal IT of visuomotor
      information occurs at the stage of controlled (perceptual and pre-motor)
      processes and rule out the possibility of an IT at the motoric stage.

PMID- 14673557
TI  - Express detection of nonylphenol in water samples by fluorescence polarization
      immunoassay.
AB  - The development of express method for detection of endocrine-disrupting chemicals
      (EDC) such as alkylphenols is required for ecological monitoring. Several
      attempts have been made to produce antibodies against 4-nonylphenol (NP) in
      recent years. This work describes the production of new antibodies against NP and
      also summarizes the characterization of antibodies obtained earlier. Three
      approaches used to produce alkylphenol-specific antibodies are compared; these
      are based on: 1. omega-(4-hydroxyphenyl)nonanoic or omega-(4
      hydroxyphenyl)heptanoic acid NP derivatives designed to mimic the linear NP
      isomer; 2. 4-aminophenol, which potentially mimics various substituted phenolic
      compounds with different side-chain structures at position 4 of the benzene ring;
      and 3. a mixture of branched NP isomers, conjugated to the carrier protein via a
      benzene ring by the Mannich reaction, and expected to be the closest mimic of NP
      structure by preserving its natural alkyl moiety.Fluorescence polarization
      immunoassays based on different combinations of antibody and labeled antigen for
      screening detection of NP were developed and structural aspects of assay
      sensitivity and specificity were investigated. The assays based on the antisera
      raised against omega-(4-hydroxyphenyl)nonanoic acid and NP conjugate via Mannich
      reaction are capable of express detection of NP with detection limit of 7 microg
      mL(-1 )and assay dynamic range of 18-300 microg mL(-1).

PMID- 14673559
TI  - Speciation of dissolved silicates in natural waters containing alkaline and
      alkaline-earth ions. A case study--waters from arid lands (North West China).
AB  - The concentration of silica in water samples from the desert area of Xinjiang, N.
      W. China, has been measured by colorimetry with ammonium molybdate. The observed
      pattern of dependence of the concentration of silica on the concentration of
      sodium ion (Na(+)) in the water samples is consistent with the pattern obtained
      by experiments on in-vitro dissolution of silica gel in sodium chloride (NaCl)
      solution. This indicates that the dissolution of silica in the hydrologic system
      in this area depends on the concentration of Na(+). Calcium ion (Ca(2+)), which
      is known to play an important role on the dissolution of silica on the basis of
      in-vitro experiments, was observed to take little part in the dissolution of
      silica in actual natural water samples. This implies that the Ca(2+) is bound to
      the hydrogen carbonate anion or that the Ca(2+) content of natural water
      containing salts is very low, owing to precipitation. In these samples silicate
      Na(+) was identified as the dissolution species of silica; it was also
      ascertained that Ca(2+) did not form complexes with silicate species. These
      observations resulted from direct identification of dissolved chemical species by
      use of FAB-MS (fast atom bombardment mass spectrometry). The research indicates
      that in water samples in this critically arid region the concentration of
      "dissolved" silica is basically determined by the concentration of Na(+),
      indicative of pure inorganic conditions in the desert area of Xinjiang, N.W.
      China.

PMID- 14673560
TI  - Magnetophoresis and electromagnetophoresis of microparticles in liquids.
AB  - The magnetic field-induced migration of particles in liquids is a highly
      promising technique for the micro-separation analysis of bioparticles, such as
      cells and large DNA. Here, new methods that make use of magnetophoresis and
      electromagnetophoresis to induce the migration of microparticles in liquids are
      briefly reviewed. Magnetic force and Lorentz force are utilized in the new
      methods. Some typical examples of the use of these methods are described, and the
      advantages of using a superconducting magnet for them are demonstrated.

PMID- 14673561
TI  - Certification of mono-, di-, and tributyltin compounds in marine sediment
      certified reference material by species-specific isotope dilution mass
      spectrometric analysis using synthesized 118Sn-labeled butyltins.
AB  - A new marine sediment reference material (NMIJ CRM 7301-a) for butyltins analysis
      was prepared and certified by the National Metrological Institute of Japan,
      National Institute of Advanced Industrial Science and Technology (NMIJ/AIST). The
      original material of the sediment was collected at a bay near industrial
      activities in Japan. The sediment material was air-dried, sieved, homogenized,
      and packaged into 1,000 glass bottles (60 g each). Certification of NMIJ CRM 7301
      a was carried out at NMIJ using two different types of species-specific isotope
      dilution mass spectrometry: isotope dilution-ethylation-gas
      chromatography/inductively coupled plasma mass spectrometry (GC/ICPMS) and
      isotope dilution-ethylation-gas chromatography/mass spectrometry (GC/MS). A
      mixture of (118)Sn-enriched monobutyltin, dibutyltin, and tributyltin was
      synthesized in our laboratory and was used as a spike for both techniques.
      Certified values are given for tributyltin (0.044+/-0.004 mg kg(-1) as Sn),
      dibutyltin (0.056+/-0.006 mg kg(-1) as Sn, and monobutyltin (0.058+/-0.013 mg kg(
      1) as Sn), being at lower levels than currently available sediment CRMs for the
      analysis of organotins.

PMID- 14673562
TI  - Natural toxins: risks, regulations and the analytical situation in Europe.
AB  - Natural toxins in food and feed are considered important food safety issues of
      growing concern, in particular mycotoxins, phycotoxins and plant toxins. Most
      scientific developments have occurred in the past few decades in the area of
      mycotoxins. Formal health risk assessments have been carried out by the Joint
      Expert Committee on Food Additives of the World Health Organization and the Food
      and Agriculture Organization. Limits and regulations for mycotoxins in food and
      feed have been established in many countries, including practically all European
      countries. An array of (formally validated) analytical methods and (certified)
      reference materials have become available. Several European research projects,
      funded by the European Commission and supported by the European Standardization
      Committee, have significantly contributed to this development. Quantitative
      methods of analysis for mycotoxins often make use of immunoaffinity cleanup with
      liquid chromatographic or gas chromatographic separation techniques in
      combination with various types of detectors, including mass spectroscopy. For
      screening purposes (bio)sensor-based techniques are among the promising
      newcomers. For the phycotoxins the situation is less advanced. Formal risk
      assessments by authoritative international bodies have not been carried out.
      Methods of analysis, formally validated according to internationally harmonized
      protocols, are scarce and animal testing still plays a key role in official
      methodology. The development of the analytical methodology is partly hampered by
      the limited availability of certain reliable calibrants and reference materials,
      although this situation is gradually improving. New regulations in the European
      Union have increased the pressure to develop and validate chemical methods of
      analysis. Joint efforts in the European context are now directed towards
      significantly improving this situation, and techniques such as liquid
      chromatography-mass spectroscopy offer promise in this respect. Both the working
      group on biotoxins of the European Standardization Committee and the network of
      National Reference Laboratories for Marine Biotoxins have taken up
      responsibilities here. The plant toxins are a category of natural toxins, where
      the situation is the least developed with respect to regulations, validated
      methods of analysis and reference materials. Yet, their occurrence in a wide
      range of consumable plant species demands the attention of the analytical
      community.

PMID- 14673563
TI  - Chemical and physical factors affecting the extractability of methidathion from
      soil samples.
AB  - Determination of methidathion in soil samples using Soxhlet extraction has been
      studied. Several factors were investigated for their effect on methidathion
      recovery. Some were related to the extraction procedure, for example solvent type
      used for the extraction (acetone or hexane/toluene), extraction time, soil
      humidity, and type of sterilisation system employed. Other factors tested
      included the addition of organic matter to the soil, for example urban sewage
      sludge and the cationic surfactant TDTMA. Experimental designs were used to
      determine the effects of the different factors. Acetone resulted in higher
      recoveries and was less affected by the presence of water. Autoclaving was the
      most appropriate sterilisation method. Thimerosal resulted in a decrease in
      insecticide recovery. Methidathion recovery increased as the amount of cationic
      surfactant was increased, but decreased as the amount of sewage sludge added to
      the soil was increased. In general, because the factors studied were not always
      independent of each other, a clear description of the methodology used is needed
      when analysing pollutants in environmental samples.

PMID- 14673564
TI  - The impact of chromatography and mass spectrometry on the analysis of protein
      phosphorylation sites.
AB  - Protein phosphorylation analysis is an enormous challenge. This review summarises
      the currently used techniques, which are based on radiolabelling and mass
      spectrometry as well as electrophoretic and chromatographic separation. Many
      methods exist, but there is still no single procedure applicable to all
      phosphoproteins. MS is able to deliver information about the location of
      phosphorylation sites, but phosphospecific properties with respect to ionisation
      present obstacles. Therefore, multidimensional approaches involving several
      analytical methods are often necessary to conquer phosphorylation site
      identification.

PMID- 14673565
TI  - LC-MS analysis in the aquatic environment and in water treatment technology--a
      critical review. Part II: Applications for emerging contaminants and related
      pollutants, microorganisms and humic acids.
AB  - Environmental contaminants of recent concern are pharmaceuticals, estrogens and
      other endocrine disrupting chemicals (EDC) such as degradation products of
      surfactants, algal and cyanobacterial toxins, disinfection by-products (DBPs) and
      metalloids. In addition, pesticides (especially their transformation products),
      microorganisms, and humic substances (HS), in their function as vehicles for
      contaminants and as precursors for by-products in water treatment, traditionally
      play an important role. The present status of the application of LC-MS techniques
      for these water constituents are discussed and examples of application are given.
      Solid-phase extraction with various non-selective materials in combination with
      liquid chromatography (LC) on reversed-phase columns have been the most widely
      used methods for sample preconcentration and separation for different compound
      classes like pesticides, pharmaceuticals or estrogens. Electrospray ionization
      (ESI) and atmospheric pressure ionization (APCI) are the most frequently used
      ionization techniques for polar and ionic compounds, as well as for less polar
      non-ionic ones. The facilities of LC-MS have been successfully demonstrated for
      different compound classes. Polar compounds from pharmaceuticals used as
      betablockers, iodinated X-ray contrast media, or estrogens have been determined
      without derivatization down to ultratrace concentrations. LC-MS can be viewed as
      a prerequisite for the determination of algal and cyanobacterial toxins and the
      homologues and oligomers of alkylphenol ethoxylates and their metabolites. Tandem
      mass spectrometric techniques and the use of diagnostic ions reveal their
      usefulness for compound-class specific screening and unknown identification, and
      are also valid for the analysis of pesticides and especially for their
      transformation products. Structural information has been gained by the
      application of LC-MS methods to organometallic species. New insights into the
      structural variety of humic substances have been made possible by FT-ICR-MS due
      to its ultrahigh mass resolution. Finally, exciting possibilities for rapid
      detection and identification of microorganisms have been made possible by MALDI
      and LC-MS methods.

PMID- 14673566
TI  - Ultratrace determination of mercury in water following EN and EPA standards using
      atomic fluorescence spectrometry.
AB  - Chemical vapour generation has been used in combination with atomic fluorescence
      spectrometry to determine mercury at ultratrace concentrations down to 0.1 ng L(
      1). A time-based injection of 1 mL of solution for measurement was sufficient to
      generate a steady-state detector response in the direct mode of measurement. The
      detection limit calculated from a ten-point calibration curve according to DIN
      32645 was 0.26 ng L(-1). Instrument noise is limited by reflected radiation from
      the light source rather than by the dark current of the photomultiplier. The
      detection limit is directly influenced by the reagent blank which was 2 ng L(-1)
      in the experiments described. Focusing by amalgamation and subsequent thermal
      desorption generates a detector response which is about eight times higher in
      peak intensity and about twice as large in integrated intensity. The detection
      limit under these conditions is 0.09 ng L(-1) which can be further improved by
      preconcentration of larger volumes of solution for measurement. The cycle time
      for one individual reading is about 40 s without amalgamation and 125 s with
      amalgamation. The linear dynamic range of the system is five orders of magnitude
      with a single photomultiplier gain setting. The carry-over is less than 0.3% in
      direct measurement mode. Reference water samples and a surface water containing
      approximately 5 ng L(-1) were used to prove the validity of the method for real
      samples. Good accuracy and recoveries of 103% were calculated using the fast
      direct determination technique.

PMID- 14673567
TI  - DNA damage and ubiquitinated neuronal inclusions in the substantia nigra and
      striatum of mice following MDMA (ecstasy).
AB  - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative,
      which is neurotoxic to both serotonin (5HT) and dopamine (DA) nerve terminals.
      Previous reports, carried out in rodents and non-human primates, demonstrated
      neurotoxicity to monoamine axon terminals, although no study has analyzed nigral
      and striatal cell bodies at the sub-cellular level. OBJECTIVE: In this study, we
      examined intrinsic nigral and striatal cells, and PC12 cell cultures to evaluate
      whether, in mice, MDMA might affect nigral and striatal cell bodies. METHODS:
      After administering MDMA, we analyzed effects induced in vivo and in vitro using
      high-performance liquid chromatography (HPLC) analysis, light- and electron
      microscopy with immunocytochemistry, and DNA comet assay. RESULTS: We found that
      MDMA (5 mg/kg x4, 2 h apart), besides a decrease of nigrostriatal DA innervation
      and 5HT loss, produces neuronal inclusions within nigral and intrinsic striatal
      neurons consisting of multi-layer ubiquitin-positive whorls extending to the
      nucleus of the cell. These fine morphological changes are associated with
      clustering of heat shock protein (HSP)-70 in the nucleus, very close to chromatin
      filaments. In the same experimental conditions, we could detect oxidation of DNA
      bases followed by DNA damage. The nature of inclusions was further investigated
      using PC12 cell cultures. CONCLUSIONS: The present findings lead to re
      consideration of the neurotoxic consequences of MDMA administration. In fact,
      occurrence of ubiquitin-positive neuronal inclusions and DNA damage both in
      nigral and striatal cells sheds new light into the fine alterations induced by
      MDMA, also suggesting the involvement of nuclear and cytoplasmic components of
      the ubiquitin-proteasome pathway in MDMA toxicity.

PMID- 14673568
TI  - A bitter pill. Overview of ecstasy (MDMA, MDA) related fatalities.
AB  - RATIONALE: The issue of ecstasy-related fatalities has extensively attracted the
      attention of both the media and the general public, but less so of the scientific
      literature. OBJECTIVES: The aim of the present review is to focus on the
      epidemiological, clinical and pharmacological issues related to ecstasy
      fatalities. RESULTS: Possibly due to a number of different reasons, the rates of
      ecstasy-related deaths seem to have peaked in recent years. MDMA metabolism is
      regulated by the levels of CYP2D6 and COMT (both exhibit some genetic
      polymorphism), and range of activity of these enzymes may account for some inter
      individual differences in terms of toxic responses to the drug. A small increase
      in MDMA dosage can lead to a significant rise in drug plasma concentration. Due
      to their tolerance to MDMA psychoactive effects, some individuals may binge with
      dosages that may be the cause of serious concern. In experienced users, a reverse
      tolerance phenomenon can also be observed. Together with ecstasy, most of the
      misusers take a number of different compounds and the possible rationale of this
      style of consumption is commented upon here. Frequently, the lethal complications
      observed after acute MDMA administration can be the consequence of the occurrence
      of a serotonin syndrome and/or of sympathomimetic overstimulation (both
      conditions are exacerbated by environmentally induced overheating). CONCLUSIONS:
      A number of methodological problems can contribute to making difficult the
      interpretation of the role played by ecstasy in so-called ecstasy-related deaths,
      especially so if accurate information is not available.

PMID- 14673571
TI  - Current classification of mitochondrial disorders.

PMID- 14673570
TI  - HLA-A, HLA-B and HLA-DR matching reduces the rate of corneal allograft rejection.
AB  - PURPOSE: The purpose of this study is to determine the effectiveness of HLA
      typing in preventing corneal allograft rejection. METHODS: This retrospective
      single-center study analyzed 459 consecutive HLA-typed patients who underwent
      perforating keratoplasty (PKP) between 1983 and 2001. Grafts were postoperatively
      transparent after donor-recipient selection by HLA-A, -B and -DR typing. Patients
      were divided into a low- and a high-risk group based on their preoperative
      diagnosis. RESULTS: The estimated 1-, 5- and 10-year graft survival (Kaplan
      Meier) was 93, 88 and 67% in low-risk patients and 73, 43 and 38% in high-risk
      patients. We found a significant correlation between the number of HLA mismatches
      and the rate of allograft rejections: a donor-recipient match of two or more
      alleles in HLA-A, -B or -DR reduces the rejection rate by at least 10% in low
      risk (10 years after PKP; P<0.04) and 40% in high-risk patients (3 years after
      PKP; P<0.0001). Especially HLA-B mismatches are important prognostic factors for
      both low- ( P<0.008) and high-risk patients ( P<0.003). Considering both HLA-B
      and -DR mismatches significantly reduces the rate of allograft rejection,
      particularly in high-risk patients ( P<0.0001). Matching on a split typing level
      offers no significant advantage over broad level matching. CONCLUSION: Clinical
      results confirm theories developed to explain the function of the HLA (MHC)
      receptor. The closest possible donor-recipient match of HLA antigens based on
      broad level typing significantly reduces the rate of allograft rejection and thus
      improves the prognosis for long-term transparency of corneal grafts in both high-
      and low-risk patients.

PMID- 14673572
TI  - Magnetic resonance studies of abnormalities in the normal appearing white matter
      and grey matter in multiple sclerosis.
AB  - Magnetic resonance (MR) techniques are of value in following the pathological
      process of multiple sclerosis in vivo. They are widely applied to monitor the
      disease natural history and its modification by treatment. However, serial
      studies of lesion measures have yielded generally disappointing correlations with
      the development of clinical disability. A potential explanation for this is the
      presence of abnormalities, beyond the visible lesions, in the normal appearing
      white matter (NAWM) and grey matter (NAGM). Quantitative structural MR
      techniques, including measures of magnetisation transfer, diffusion, relaxation
      times and spectroscopic metabolite concentrations, reveal that there are
      abnormalities in NAWM and NAGM. These are present from clinical onset and become
      more pronounced with clinical progression, increasing disability and increasing
      lesion load. Furthermore, functional MRI (fMRI) studies of motor and visual
      paradigms has identified a range of responses suggesting that cortical plasticity
      exists; such modified responses are seen in the earliest stages of disease and in
      the absence of visible lesions, but are more pronounced with disease progression
      and increasing lesion load and abnormality in the NAWM. Limited reproducibility
      and sensitivity to change can pose methodological limitations for MR studies of
      NAWM and NAGM, especially when follow up intervals are relatively short. Whilst
      existing quantitative MR measures from normal appearing tissues provide valuable
      information to understand the natural history and monitor treatment effects in
      MS, none of them fully or even predominantly accounts for the patient's
      functional state nor can be relied on as a definitive surrogate measure of
      treatment effect. Better resolution of the abnormalities is needed especially in
      grey matter where pathological foci are known to be abundant. Studies correlating
      structural MR and fMRI parameters with measures of function in well defined
      anatomical pathways should further elucidate the pathogenic role of abnormality
      in the normal appearing tissues. In future, new imaging modalities are needed
      that provide a more specific measure of histopathological and cellular aspects of
      the disease process in vivo.

PMID- 14673573
TI  - Opsoclonus-myoclonus-dysequilibrium syndrome: cytological and immunological
      dynamics in the serial cerebrospinal fluid in two patients.
AB  - A peculiar clinical presentation characterized by the triad of
      opsoclonus,myoclonus and ataxia, mainly in a form of dysequilibrium, is usually
      associated with infectious or paraneoplastic processes. Serial cerebrospinal
      fluid (CSF) analysis in two patients with opsoclonus-myoclonus-dysequilibrium
      syndrome suggestive of viral encephalitis were performed from disease onset for
      up to 8 months. A cell count, cytology, total protein and glucose concentrations
      in CSF, the blood-CSF barrier function, intrathecal synthesis of immunoglobulins
      (Ig) in class M, G and A expressed as IgM, IgG and IgA indices and oligoclonal
      IgG bands were monitored. Cellular and humoral alterations in both patients were
      slight at the onset becoming more pronounced a month later. The kinetics of the
      CSF changes mirrored the subacute clinical deterioration and subsequent recovery.
      The delayed response in the CSF measures and the gradual clinical deterioration
      suggest the development of subacute brain inflammation. A mononuclear
      pleocytosis, including macrophages and plasma cells, increased within the first
      month and then normalized during the following weeks. Intrathecally synthesized
      IgM occurred only transiently after one month of illness, whereas intrathecal IgG
      production increased during the first month and persisted for at least eight
      months. An increasing number of oligoclonal IgG bands during the course,
      indicative of expanding local intrathecal synthesis, was noted. The dynamics of
      these CSF changes supports the hypothesis that opsoclonus-myoclonus syndrome is a
      post-infectious immune- mediated condition.

PMID- 14673574
TI  - Neurological associations of absent P60 component of the posterior tibial nerve
      somatosensory evoked potential.
AB  - The cortically generated P60 component of the posterior tibial nerve
      somatosensory evoked potential (PTSEP) is occasionally found to be absent in
      neurological patients,while the preceding P40 is preserved ("Absent P60"
      pattern). A retrospective analysis of 24 such cases showed them to represent a
      different clinical population from that represented by 24 age- and sex-matched
      but otherwise unselected patients with entirely normal PTSEPs. The most frequent
      diagnoses of the patients with normal PTSEPs (conversion disorder and definite or
      suspected multiple sclerosis) were significantly less prevalent in the patients
      with the Absent P60 pattern, while miscellaneous other diseases affecting the
      peripheral and/or central sensory pathways were more frequent. In comparison with
      a second matched patient group with abnormal P40 in addition to P60, the patients
      with the Absent P60 pattern had a significantly lower incidence of "large fibre"
      sensory deficits (impaired vibration and/or joint-position sense). The incidence
      of "small fibre" deficits (impaired pain and/or temperature sensation) was
      similar in both groups with PTSEP changes. In conjunction with previously
      published findings in normal subjects, the data suggest that the P60 is a late
      response of the primary sensorimotor cortex due to activation of large diameter
      myelinated sensory fibres, but which is also tonically influenced by small fibre
      input. The Absent P60 pattern may be recognized as a distinct PTSEP abnormality,
      although its occurrence in some normal individuals should be noted.

PMID- 14673575
TI  - Variable reduction of caveolin-3 in patients with LGMD2B/MM.
AB  - Mutations in the human dysferlin gene ( DYSF) cause autosomal recessive muscular
      dystrophies characterized by degeneration and weakness of proximal and/or distal
      muscles: limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy
      (MM). Recently, an interaction between caveolin-3 and dysferlin in normal and
      dystrophic muscle (primary caveolin-3 deficiency; LGMD1C) was shown. In this
      study, clinical,morphological and genetic analysis was carried out in four
      independent LGMD2B/MM patients. All patients presented with an adult-onset,
      slowly progressive muscular dystrophy with variable involvement of proximal and
      distal muscles. We found complete lack of dysferlin in the four LGMD2B/MM
      patients. Secondary reduction of caveolin-3 was detected in three out of the four
      patients. Regular caveolae were detected along the basal lamina in two patients
      by electron microscopy. We provide further evidence that dysferlin and caveolin-3
      interact in human skeletal muscle. It remains to be elucidated whether the loss
      of this interaction contributes to pathogenic events in muscular dystrophy.

PMID- 14673576
TI  - Driving in Parkinson's disease - a health hazard?
AB  - BACKGROUND: The driving safety of Parkinson's disease (PD) patients has lately
      been questioned after several authors reported road accidents caused by sleep
      attacks in PD patients on dopaminergic medication. OBJECTIVES: To determine 1)
      whether PD patients in general and those on dopaminergic medication in particular
      are especially prone to cause severe road accidents and 2) whether there are PD
      symptoms or dopaminergic side effects with the potential to compromise driving
      safety. DATA SOURCE: Relevant articles were identified by electronic search of
      biomedical databases (1966-2002: MEDLINE, EMBASE, PASCAL, PUBMED), the Cochrane
      Controlled Trials Register, and reference lists of located articles. RESULTS:
      Despite frequent occurrence of potentially hazardous dopaminergic side effects (2
      57 %) and disabling parkinsonian non-motor and motor disabilities (16-63 %), the
      two existing studies on accident rates suggest that PD patients are not more
      prone to cause road accidents than the rest of the population. Five further
      reports including 1346 patients and focusing on dopaminergically induced sleep
      attacks provided comparably low accident figures (yearly incidence: 0%-2%).
      Because of low figures meta-analysis was intended but finally deemed
      inappropriate as the methodology of included studies varied greatly and was
      frequently flawed. CONCLUSION: Further prospective community-based well designed
      studies on accident risk in PD patients are needed to provide evidence based
      driving recommendations.

PMID- 14673577
TI  - Prospective study of patients presenting with acute partial transverse
      myelopathy.
AB  - BACKGROUND: The clinical and radiological characteristics of myelopathy in
      multiple sclerosis (MS) are relatively well known. Nevertheless, it remains
      difficult for the clinician to ascertain conversion to MS after a first episode
      of acute partial transverse myelopathy (APTM). OBJECTIVE: The aims of this study
      were to define predictive factors for conversion to clinically definite MS after
      an APTM and to define predictive factors for disease severity. PATIENTS AND
      METHODS: Between 1994 and 2001, we prospectively included 55 patients presenting
      with a first episode of APTM. Three patients were lost during the follow-up. We
      evaluated clinical signs, spinal cord and brain MRI, cerebrospinal fluid (CSF)
      and visual evoked potentials on admission. After a mean followup of 35 months
      (range 12-86), we evaluated the diagnosis and, among the MS group, the severity
      of the disease. RESULTS: Of the 52 APTM patients who completed the study, 30
      became clinically definite MS. The predictive factors for conversion to MS were:
      initial sensory symptoms, latero-posterior spinal cord lesion, abnormal brain MRI
      and oligoclonal bands in CSF. In the MS group, the number of spinal cord lesions
      on MRI was the only predictive factor for a poor outcome, being statistically
      correlated with a higher number of relapses. CONCLUSION: On the basis of our
      results, we propose that, in patients with APTM, sensory symptoms, oligoclonal
      bands and brain MRI are predictive factors for subsequent conversion to
      clinically definite MS and that within the latter patients the number of spinal
      cord lesions on MRI is the only predictive factor for a poor outcome.

PMID- 14673578
TI  - Olfactory dysfunction in cerebellar ataxia and multiple system atrophy.
AB  - BACKGROUND: Olfactory dysfunction has been reported in Parkinson's (PD) and
      Alzheimer's disease (AD). OBJECTIVE: We studied olfactory function in eight
      patients with multiple system atrophy of cerebellar type (MSA-C), eleven patients
      with sporadic cerebellar ataxia of unknown etiology and thirteen controls matched
      for age and gender. Subjects received tests for n-butanol odor thresholds, odor
      identification, and odor discrimination. RESULTS: Olfactory thresholds were
      abnormally high in 16% of the patients. Odor discrimination and odor
      identification were impaired in 44 % and 74% of the patients, respectively. There
      was no significant difference in olfactory function between patients with
      sporadic ataxia of unknown etiology and MSA-C patients. CONCLUSIONS: The present
      data suggest that olfactory dysfunction is common to various neurodegenerative
      disorders and not specifically restricted to PD or AD. Cerebellar dysfunction
      affected suprathreshold olfactory function more severely than odor thresholds.
      Thus cerebellar lesions may affect the processing of odor-related information to
      a higher degree than the transport of odorants to the receptor through sniffing.

PMID- 14673579
TI  - Cognitive impairment: a key feature of congestive heart failure in the elderly.
AB  - Congestive heart failure (CHF) has been proposed as a possible cause of cognitive
      dysfunction but only a few studies have directly assessed cognitive performance
      in CHF. The aim of the present study was to compare the cognitive patterns of
      patients with CHF and patients having cardiovascular diseases uncomplicated by
      CHF (no-CHF group). In a multicenter observational case-control study, we studied
      149 hospitalized elderly CHF patients in the New York Heart Association (NYHA)
      class II (CHFm, m: moderate), 159 CHF patients in NYHA class III-IV (CHFs, s:
      severe), and 207 no-CHF patients. Patients underwent a multidimensional
      assessment and neuropsychological tests for the following cognitive domains:
      attention, visual-spatial intelligence, verbal attainment, verbal and visuo
      spatial memory. Neuropsychological performances of groups were compared by
      multivariate analysis. Correlates of an abnormal performance on at least three
      neuropsychological tests were assessed by logistic regression analysis. CHFs
      performed worse than no-CHF patients on 4 of the 7 neuropsychological measures,
      the largest difference being in tests of attention and verbal learning (p <
      0.001). Prevalence of abnormal performance on at least 3 tests was 57.9 % in
      CHFs, 43% in CHFm and 34.3 % in no-CHF groups (chi square = 17.3, p < 0.0001).
      The following qualified as independent correlates of the outcome at logistic
      regression analysis: CHFs group membership (Odds Ratio-OR = 2.56, 95% Confidence
      Interval-CI = 1.49-4.40), depression (OR = 2.37, 95% CI = 1.54-3.66),
      hypertension (OR = 1.88, 95% CI = 1.18-2.99). Our results demonstrate that
      cognitive impairment is common among CHF patients and seems to be causally
      related to CHF severity, depression and hypertension. The cognitive dysfunction
      also characterizes a relevant fraction of patients with cardiovascular diseases
      uncomplicated by CHF.

PMID- 14673580
TI  - Does improved problem-based teaching influence students' knowledge at the end of
      their neurology elective? An observational study of 40 students.
AB  - BACKGROUND: Elective programs for medical students in the last year of their
      university training are poorly evaluated. The goal of this study was to determine
      the gain in theoretical and practical skills in a group of students during their
      elective in neurology. Students were trained by either conventional teaching
      methods or applying improved problem-based teaching. METHOD: A test of 78
      multiple choice questions regarding both, theoretical and practical aspects of
      clinical neurology, was presented to 21 students (9 female, 12 male). This group
      of students (group A) was trained according to the conventional teaching method.
      A subsequent group of students (intervention group B; n = 19; 9 female; 10 male)
      was educated using a modified teaching method that consisted of more problem
      based learning, gathering experience with neurosonological and neurophysiological
      principles and in intense bedside teaching. The test was performed at the
      beginning and end of their elective period. The percentage increase in the tests
      was taken as the primary endpoint. In addition, all students were asked about
      their degree of satisfaction with the elective in general. RESULTS: Students of
      both groups did not differ with regard to age, gender, number of semesters, score
      of last examination and score of the test at the beginning of the elective.
      However, students who participated in the problem-based teaching group (group B)
      performed significantly better in the test at the end of the elective (increase
      16.3% +/- 15.5) than those who were trained according to the conventional
      teaching program (percentage increase 6.3% +/- 9.4; p = 0.017). Students of both
      groups were highly satisfied with the elective in general. CONCLUSION: More
      problem-based teaching including practical exercises and intense bed-side
      teaching significantly improved students' performance. Thus, adaptation of
      teaching covering these aspects should be encouraged and might improve the
      neurological knowledge and skills of the students.

PMID- 14673581
TI  - Assessment of complex movements reflects dysfunction in Huntington's disease.
AB  - Results of various complex instrumental tools, rating scales, caudate atrophy and
      CAG repeat length may reflect the severity of Huntington's disease (HD). A simple
      assessment task for dysfunction due to disease is the standardized, computer
      based performance of peg insertion. The objectives of our study were to compare
      scored HD symptoms, computed bicaudate diameter ratio (BDR), age related genetic
      disease load (CAG index = [CAG-35.5 x age]) and peg insertion scores between
      asymptomatic 34 HD gene carriers, 89 previously untreated HD patients with
      psychiatric or motor symptoms, or both, and 51 treated HD patients. We measured
      the period of the total time taken to insert 25 pegs from a rack into a series of
      appropriate holes, calculated the CAG index, estimated the bicaudate diameter
      ratio (BDR) of a current brain CT and scored the HD patients under blind
      conditions. Times for the peg insertion task significantly differed between HD
      patients and controls, but not between HD gene carriers and controls. BDR and CAG
      index reflected the increase of symptoms in HD. Peg insertion results and scored
      severity of HD, BDR and CAG index significantly correlated with each other. Peg
      insertion scores are not specific diagnostic markers for HD, but they reflect
      clinical symptoms of neurodegeneration. The performance of peg insertion involves
      visuospatial cognition, self-elaboration of internal strategies, sorting and
      planning of movement. Therefore peg insertion particularly reflects executive
      dysfunction in early HD and additionally motor impairment in advanced HD.

PMID- 14673582
TI  - Assessing dopaminergic function in Parkinson's disease: levodopa kinetic-dynamic
      modeling and SPECT.
AB  - Levodopa pharmacokinetic-phamacodynamic (PK-PD) modeling may be able to test the
      functional integrity of the nigrostriatal dopaminergic system in Parkinson's
      disease (PD). [(123)I]-FP-CIT SPECT imaging of striatal dopamine transporters has
      also been introduced for the evaluation of presynaptic dopaminergic homeostasis.
      We aimed to assess the intrapatient relation between levodopa PK-PD and SPECT
      measures of dopaminergic function in PD. Thirty-five PD patients, 1 to 4 on the
      Hoehn and Yahr (H&Y) scale, enrolled in the study. Each patient was examined by
      levodopa PK-PD modeling and SPECT imaging. Primary measure outcomes were the
      levodopa half-life in the effect compartment (t1/2(eq)) for PKPD modeling and the
      ratio of specific to non specific (SP/NSP) tracer striatal uptake for SPECT.
      Levodopa t1/2(eq) was highly significantly correlated with H&Y scale (r = -0.815,
      p < 0.0001), Unified Parkinson's disease Rating Scale (UPDRS) (r = -0.691, p <
      0.0001) and PD symptom duration (r = -0.647, p < 0.0001). SPECT contralateral
      putamen SP/NSP ratio showed the most significant correlations with clinical
      indicators of disease severity: H&Y, r = -0.526, p < 0.002; UPDRS, r = -0.523, p
      < 0.002; symptom duration, r = -0.513, p < 0.002. Significant correlations were
      observed between levodopa t1/2(eq) and putamen SP/NSP ratios, yielding the
      closest correlation for the contralateral region (r = 0.522, p < 0.002). An
      indirect PK-PD dopaminergic functional variable and direct SPECT measures of
      presynaptic dopaminergic system homeostasis were in close agreement with clinical
      data and correlated to each other. Levodopa PK-PD modeling can be a practical
      clinical tool indirectly assessing the functional integrity of the nigrostriatal
      dopaminergic system in PD patients.

PMID- 14673583
TI  - The cerebellum and cognition. Intellectual function in spinocerebellar ataxia
      type 6 (SCA6).
AB  - The aim of this study was to assess cognitive function in patients with
      spinocerebellar ataxia type 6 (SCA6), an autosomal-dominantly inherited disease
      leading to a progressive cerebellar syndrome. In contrast to other SCA types, the
      pathological changes are mostly restricted to the cerebellum. Cognitive function
      was studied in 12 patients with genetically confirmed SCA6 (mean duration of
      disease: 9.2 +/- 11.6 years) and 12 age- and IQ-matched controls using a test
      battery comprising tests for IQ, attention, verbal and visuospatial memory, as
      well as executive function. While none of the SCA6 subjects had features of
      general intellectual impairment, only mild deficits in single subtests especially
      in fronto-executive tasks were observed, but without reaching statistical
      significance. Thus the current findings do not demonstrate severe cognitive
      dysfunction in SCA6.

PMID- 14673584
TI  - Multiple vascular abnormalities and a paradoxical combination of vitamin B12
      deficiency and thrombocytosis in a case with POEMS syndrome.
AB  - POEMS/Crow-Fukase syndrome is a rare multisystem disorder associated with
      elevated vascular endothelial growth factor (VEGF), which clinically presents
      with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes.
      We report a case of POEMS syndrome due to a gammopathy of undetermined
      significance with thrombocytosis, vitamin B(12) deficiency, highly elevated VEGF
      and in addition to glomeruloid angiomas two previously undescribed proliferative
      vascular lesions: a spinal arteriovenous fistula and a plexogenic pulmonary
      arteriopathy, which ultimately resulted in lethal pulmonary hypertension. We
      assume that the high VEGF levels caused the vascular abnormalities observed in
      our patient.

PMID- 14673585
TI  - Zoster paresis with Horner's syndrome.

PMID- 14673586
TI  - Pramipexole in Restless Legs syndrome. Evaluation by suggested immobilization
      test.

PMID- 14673587
TI  - Cerebral microbleeds in Alzheimer's disease.

PMID- 14673589
TI  - Persistent organic personality change as rare psychiatric manifestation of MELAS
      syndrome.

PMID- 14673588
TI  - Familial mtDNA T8993C transition causing both the NARP and the MILS phenotype in
      the same generation. A morphological, genetic and spectroscopic study.

PMID- 14673590
TI  - Drug induced aseptic meningitis due to diclofenac.

PMID- 14673591
TI  - Mustafa Hayrullah Diker (1875-1950).

PMID- 14673598
TI  - Animal model of sclerotic skin. VI: Evaluation of bleomycin-induced skin
      sclerosis in nude mice.

PMID- 14673599
TI  - Pathological changes of the myonuclear fibrous lamina and internal nuclear
      membrane in two cases of autosomal dominant limb-girdle muscular dystrophy with
      atrioventricular conduction disturbance (LGMD1B).
AB  - Mutations in the lamin A/C gene have been reported in a variety of disorders
      including autosomal dominant Emery-Dreifuss muscular dystrophy and autosomal
      dominant limb girdle muscular dystrophy with cardiac conduction block or limb
      girdle muscular dystrophy type 1B (LGMD1B). However, how these mutations are
      involved in developing these diseases is not known. We examined morphological
      changes of the skeletal muscle in two cases of LGMD1B in a family, directing our
      attention to the nuclear envelope and its underlying structures where lamin A/C
      is located. Although conventional fluorescence microscope revealed no discernible
      abnormality in the distribution of emerin and lamin A/C, a serial multi-layer
      scanning with confocal laser scanning microscope showed an attenuated and uneven
      distribution of lamin A/C. Furthermore, under an electron microscope, the nuclear
      fibrous lamina and inner nuclear membrane were relatively indistinct compared to
      controls. These changes in the myonuclei may be related to pathomechanisms of the
      present cases.

PMID- 14673600
TI  - Differentially expressed genes in neurofibromatosis 1-associated neurofibromas
      and malignant peripheral nerve sheath tumors.
AB  - Neurofibromas represent one of the hallmarks of neurofibromatosis 1 (NF1)
      patients. Tumor progression of neurofibromas to malignant peripheral nerve sheath
      tumors (MPNST) is a frequent and life threatening complication. To learn more
      about processes involved in malignant transformation, we evaluated differential
      gene expression in plexiform neurofibroma and MPNST from the same NF1 patient.
      Suppression subtractive hybridization (SSH) yielded 133 differentially expressed
      genes confirmed by reverse Northern blotting. Virtual Northern blots were
      employed to validate 23 genes. To independently verify differential expression,
      immunohistochemical analyses with antibodies to matrix metalloproteinase 13
      (MMP13), platelet-derived growth factor receptor alpha (PDGFRA) and fibronectin
      (FN1) were performed on 9 dermal and 9 plexiform neurofibromas and 16 MPNST from
      19 NF1 patients. All three proteins proved to be up-regulated in MPNST. MMP13
      expression was observed in 44% of MPNST but was absent in neurofibromas. PDGFRA
      was expressed in all tumors, but the number of cells expressing it was below 30%
      in neurofibromas and over 50% in MPNST. Likewise, FN1 was expressed in all
      tumors, but less than 30% of the cells in neurofibromas and more than 70% of the
      cells in MPNST exhibited antibody binding. Our data point to several genes not
      previously recognized to be differentially expressed, and provide a framework for
      future studies on progression-associated gene expression in low- and high-grade
      nerve sheath tumors.

PMID- 14673601
TI  - Regional alteration of synapsin I in the hippocampal formation of Alzheimer's
      disease patients.
AB  - Synapsin I is a synaptic vesicle-associated protein, participating in synapse
      formation, regulation of the synthesis of other synaptic vesicle proteins and
      promotion of neurotransmitter release. The aim of present study was to detect
      whether regional alteration of synapsin I occurred in the hippocampal formation
      of Alzheimer's disease (AD) patients. Samples of hippocampus from ten female AD
      patients and ten non-demented female controls, matched for age and postmortem
      delay, were investigated immunocytochemically. Using immunofluorescence labeling
      and laser confocal imaging, we examined the distribution of synapsin I in the CA1
      and CA3 subfields of the hippocampus and the dentate gyrus (DG) in AD patients
      and controls. The results showed that synapsin I was significantly decreased in
      the stratum radiatum of CA1 subfield and the molecular layer of DG in AD
      patients. No difference between the two groups in the intensity of synapsin I
      staining was observed in the stratum pyramidale of CA1, where a number of
      pretangles stained by Alz-50 were observed in AD patients. These results suggest
      that there is regional loss of synapsin I in the hippocampal formation of AD
      patients.

PMID- 14673602
TI  - Platelet aggregation, thromboxane production and thrombogenic ratio in
      postmenopausal women consuming high oleic acid-sunflower oil or palmolein.
AB  - BACKGROUND: Saturated fatty acids exert controversial effects on platelet
      aggregation and eicosanoid production. AIM: To investigate the effect of a
      dietary exchange between palmitic acid and oleic acid on both platelet
      aggregation and thromboxane B2 (TXB(2)) production, and on urine TXB(2),
      prostacyclin I2 (PGI(2) as 6-keto-protaglandin F(1)alpha), and the thrombogenic
      ratio (TXB(2)/6-keto-protaglandin F(1)alpha) in fourteen postmenopausal women.
      EXPERIMENTAL DESIGN: Women were assigned to two consecutive 28-d dietary periods
      that were high in cholesterol (~400 mg/d) and fat (~46%en). In the first period
      all subjects followed an oleic acid-rich diet prepared with high oleic
      acidsunflower oil. This was followed by a second period rich in palmitic acid in
      the form of palmolein. DETERMINATIONS: Nutrient intakes, ADP-platelet
      aggregation, platelet TXB(2) production, urine TXB(2) and 6-keto-protaglandin
      F(1)alpha were measured during two dietary periods and the results obtained
      correlated to serum cholesterol, lipoproteincholesterol and peroxides,
      apolipoproteins and plasma tocopherol. RESULTS: The palmolein diet led to an
      increase in the platelet aggregation rate (p < 0.05) and in the time for the
      maximal aggregation rate (p < 0.02). No significant differences were observed in
      platelet TXB(2) production. Palmolein increased urine TXB(2) in pg/mL (p < 0.05)
      and pg/min (p < 0.01), whereas the thrombogenic ratio (TXB(2)/6-keto-protaglandin
      F(1)alpha) did not change. Most changes were related to oil change, few to serum
      cholesterol level (< or > or = 6.2 mmol/L) or age (< or > or = 65 yr).
      CONCLUSIONS: Palmolein diet activates platelet aggregation more in
      normocholesterolemics. Though palmolein increased thromboxane and tended to
      increase prostacyclin in urine in normo- and hypercholesterolemic women, the
      thrombogenic ratio did not change. These effects were related to the LDL and HDL
      concentration increases and to the absence of change in the total cholesterol/HDL
      cholesterol ratio found following the dietary intervention.

PMID- 14673603
TI  - Prevention of brain protein and lipid oxidation elicited by a water-soluble
      oryzanol enzymatic extract derived from rice bran.
AB  - BACKGROUND: The antioxidant capacity of rice bran (RB) (due mainly to its gamma
      oryzanol content) is very well known. We have recently developed a water-soluble
      oryzanol enzymatic extract (WSOEE), which shows a greatly increased
      functionality. AIM OF THE STUDY: The aim of our study is the evaluation of the
      antioxidant potential of WSOEE in an ex vivo model to compare its protective
      capacity against oxidative damage by active-oxygen substances and free radicals
      (mainly the peroxyl radical) to biomolecules (such as proteins and lipids) with
      that of antioxidants, such as Trolox (a water-soluble derivative of vitamin E),
      melatonin, and folic acid. METHODS: WSOEE gamma-oryzanol content and composition
      were determined by HPLC. Free-radical-scavenging capacity was evaluated using the
      assay based on phycoerythrin fluorescence. Antioxidant capacity against
      hydroperoxide-caused oxidative injury to proteins and lipids was evaluated using
      an ex vivo model: a rat brain homogenate. The effectiveness was determined by
      assessing protein damage (measured as carbonyl group content by Western blot
      immunoassay) and lipid peroxidation (measured as malondialdehyde content).
      RESULTS: The WSOEE gamma-oryzanol composition profile was similar to that of RB
      (cycloartenyl, 24-methylene cycloartenyl, campesteryl, and sitosteryl ferulates),
      but with two major differences: WSOEE gamma-oryzanol concentration was five times
      higher than that of RB, and WSOEE was water soluble. WSOEE total antioxidant
      capacity to trap the peroxyl radical was high, and similar to that of Trolox. The
      capacity to inhibit lipid peroxidation induced by cumene hydroperoxide in rat
      brain homogenate yielded a protection similar to that of Trolox. WSOEE also
      showed the capacity to protect protein from oxidation phenomena in rat brain
      homogenate, with a behavior similar to that of melatonin. This is of particular
      importance, since the loss of protein function caused by oxidative modification
      may affect the activity of enzymes, receptors, and membrane transporters, among
      other functions. CONCLUSION: WSOEE is a new potential antioxidant agent from rice
      bran that shows a high free-radical-scavenging capacity and prevents protein
      oxidation and lipid peroxidation when cells ex vivo are exposed to free radicals.

PMID- 14673604
TI  - Comparison of the postprandial chylomicron carotenoid responses in young and
      older subjects.
AB  - BACKGROUND: The plant carotenoids may contribute to the beneficial health effect
      of fruits- and vegetables-rich diet. Epidemiological studies consistently
      associated high plasma carotenoids status with reduced age-related diseases.
      However, the data concerning the bioavailability of carotenoids in the elderly
      are scarce. OBJECTIVE: To test whether there is an age effect on carotenoid
      bioavailability. DESIGN: Eight young (20-35 y) and eight older (60-75 y) healthy
      adults ingested three different meals containing 40 g triacylglycerols (TG) and
      vegetable sources of carotenoids. These sources were either 188 g carrot puree
      which provided 30 mg betacarotene as the main carotenoid, or 61 g tomato puree
      providing 30mg lycopene, or 260 g cooked chopped spinach providing 30 mg lutein.
      TG and carotenoids were assayed in chylomicrons (CM) collected for 9 h
      postprandially. RESULTS: There was no major effect of age on the postprandial
      CM/TG response (0-9 h area under the curve (AUC)). There was no major effect of
      age on the postprandial CM all- trans beta-carotene, cis betacarotene, alpha
      carotene, and lutein responses. Adjustment of these responses by the CM TG
      responses did not reveal any age effect. While there was no significant effect of
      age on the CM lycopene response, the CM TG-adjusted lycopene response was
      significantly lower (-40 %) in the older than in the younger subjects (P < 0.04).
      The cis-trans ratios of CM betacarotene were not significantly different between
      the old and the young subjects. There was no significant effect of age on the
      ratio of CM retinyl-palmitate to the sum of alpha-carotene and beta-carotene
      measured after the carrot meal. CONCLUSIONS: The bioavailability of lycopene is
      apparently impaired in the old,while there is no major difference in the
      bioavailability of beta-carotene, alpha-carotene and probably lutein. There is
      also no major effect of age on the cis-trans isomerization of beta-carotene
      during absorption, and in the intestinal conversion of provitamin A carotenoids
      into vitamin A.

PMID- 14673605
TI  - Effect of an omega-3 fatty acid containing lipid emulsion alone and in
      combination with 5-fluorouracil (5-FU) on growth of the colon cancer cell line
      Caco-2.
AB  - BACKGROUND: In this study we examined the effects of a fish oil-based lipid
      emulsion (FO) rich in omega-3 fatty acids, which is used in humans as a component
      of parenteral nutrition, on the growth of the colon cancer cell line Caco-2. AIM
      OF THE STUDY: The aim of the present study was to investigate whether the FO
      influences growth and chemosensitivity of the colon cancer cell line Caco-2. FO
      was tested alone and in combination with the anticancer drug 5-fluorouracil (5
      FU). METHODS: Cell numbers were determined with crystal violet staining, cell
      cycle distribution was assessed using a flow cytometer and apoptosis was
      visualized by staining nuclei with diamino-phenylindole hydrochloride. RESULTS:
      FO inhibited growth of Caco-2 cells in a time and dose dependent manner. FO
      treatment evoked apoptosis as confirmed by cell morphology. Cell cycle analysis
      identified an accumulation of cells in the G(2)/M phase after incubation with FO.
      The combined treatment of the cells with FO and 5-FU resulted in a significant
      enhancement of the growth inhibition seen after exposure to either substance
      alone. Treatment of the cells with 5-FU specifically blocked the cell cycle in
      the S phase. The combined treatment of 5-FU with FO showed a further increase in
      the accumulation of cells in the S phase. CONCLUSIONS: In conclusion, FO has a
      potent antiproliferative effect on Caco-2 cells, at least in part, due to a
      decrease in the progression of the cell cycle and the induction of apoptosis. The
      combination of FO with 5-FU results in an additive growth inhibitory effect.

PMID- 14673606
TI  - The effect of a vegetarian and different omnivorous diets on urinary risk factors
      for uric acid stone formation.
AB  - BACKGROUND: About 10-15% of all urinary stones are composed of uric acid. A high
      urinary uric acid excretion, a low urine volume and an acidic urinary pH value
      are suggested to be the most important risk factors for uric acid stone
      formation. AIM OF THE STUDY: The effect of a vegetarian diet and different
      omnivorous diets on the risk of uric acid crystallization was investigated.
      METHODS: Ten healthy male subjects ingested a self-selected meat-containing diet
      (SD) for two weeks, and three different standardized diets for a period of 5 days
      each. The Westerntype diet (WD) was representative of the usual dietary
      habits,whereas the balanced omnivorous diet (OD) and the ovo-lacto-vegetarian
      diet (VD) were calculated according to the requirements. RESULTS: The risk of
      uric acid crystallization was highest on the ingestion of diets SD and WD, due to
      the high urinary uric acid excretion and the acidic urinary pH. The relative
      supersaturation with uric acid declined significantly by 85% on the intake of
      diet OD, consequent to the decrease in uric acid excretion and concentration and
      the increase in urinary pH value. The ingestion of the vegetarian diet VD led to
      a further significant reduction in the risk of uric acid crystallization by 93%
      compared to diet WD. CONCLUSIONS: The results indicate that the intake of a
      balanced vegetarian diet with a moderate animal protein and purine content, an
      adequate fluid intake and a high alkali-load with fruits and vegetables results
      in the lowest risk of uric acid crystallization compared to the omnivorous diets.

PMID- 14673607
TI  - Beta-carotene bioavailability from differently processed carrot meals in human
      ileostomy volunteers.
AB  - BACKGROUND: Carotenoids contribute to the beneficial effects of fruits and
      vegetables consumption; however, the bioavailability of these compounds from
      fresh or processed foods is not well established. AIM OF THE STUDY: We evaluated
      the bioavailability of beta-carotene (15 mg) from a single meal composed of
      cooked, pureed carrots and compared it to raw, chopped carrots. METHODS: Test
      meals were given to overnight-fastedileostomy volunteers (n = 8) along with
      skimmed-milk yogurt containing 40 g of added sunflower oil. Blood and complete
      ileal effluent samples were collected over a 24 h period. Samples were solvent
      extracted and the beta-carotene content measured by HPLC. RESULTS: Kinetics of
      excretion of cis and trans beta-carotene were similar. More beta-carotene was
      absorbed from puree as compared to raw carrots. Carotenoid mass-balance
      calculations indicated that 65.1 +/- 7.4% of the beta-carotene was absorbed from
      cooked pureed carrot meals, vs. 41.4 +/- 7.4 % from raw, chopped carrot meals.
      Gastrointestinal transit parameters did not differ significantly among the
      volunteers. As expected, the calculated lag phase was five times longer for raw
      vs. cooked carrots. Mean t-end, t-1/2 and rate of mass transit resulted in
      similar values for both raw and cooked carrot meals. A moderate response in
      carotenoid plasma profile was observed for cooked carrot test meals. CONCLUSIONS:
      Significantly more beta-carotene was absorbed from meals containing cooked,
      pureed carrots than from meals containing the raw vegetable. Moderate carotenoid
      plasma response was detected within 6 h following the administration of cooked
      processed carotenoid-containing single meal.

PMID- 14673608
TI  - Effect of diets fortified with tomatoes or onions with variable quercetin
      glycoside content on azoxymethane-induced aberrant crypt foci in the colon of
      rats.
AB  - BACKGROUND: Onion and tomato are vegetables widely consumed by humans and
      epidemiological studies show an inverse association between vegetable consumption
      and colon cancer risk; however, the effect on colon cancer of diets containing
      high levels of vegetables like onion and tomato are not clear. AIMS OF THE STUDY:
      To investigate whether tomatoes and onions,with low or high quercetin-glycoside
      content, could reduce azoxymethane (AOM)-induced Aberrant Crypt Foci (ACF),
      preneoplastic lesions in the colon of rats. METHODS: Male Fisher 344 rats were
      fed the following diets: a) high fat (HF) diet (control diet); b) HF diet
      containing 20 % (w/w) tomatoes with a low quercetin-glycoside content (final
      concentration in the diet: 5 mg/kg of quercetin aglycone equivalents); c) HF diet
      containing 20% (w/w) high quercetin-glycoside tomatoes (100 mg/kg final
      concentration of quercetin aglycone equivalents); d) HF diet containing 20 %
      (w/w) low quercetin-glycoside onions (14 mg/kg of quercetin aglycone equivalents
      in the diet); e) HF diet containing 20 % (w/w) high quercetin-glycoside onions
      (360 mg/kg quercetin aglycone equivalents in the diet). After 2 wks of feeding,
      all rats were treated twice, 1 wk apart, with AOM (12 mg/kg, s. c.). The dietary
      treatments continued until sacrifice, 7 wks after the first injection with AOM.
      RESULTS: ACF induction did not vary in animals fed low or high quercetin
      glycoside tomatoes relative to controls. On the contrary, rats fed 20% (w/w)
      onion-based diets, with low or high quercetin-glycoside content, showed an
      increase in number, multiplicity and "large" ACF compared to the control group
      (number of ACF/colon 145 +/- 15 (SE), 255 +/- 11 and 218 +/- 16 in controls, low
      and high-quercetin-glycoside groups, respectively; p < 0.01). Proliferative
      activity of the colon did not vary between animals fed control and high quercetin
      glycoside tomato diet. The height of the crypts in normal mucosa of rats fed high
      quercetinglycoside onions was significantly increased compared to control rats
      (cells/emicrypt 38.4 +/- 1.2 (SE) and 41.3 +/- 0.6 in controls and high quercetin
      glycoside onions group, p < 0.05). CONCLUSIONS: None of the diets supplemented
      with onion or tomato with variable quercetin-glycoside content demonstrated a
      potential chemopreventive effect on ACF-induction by AOM in rats.

PMID- 14673609
TI  - Micronutrient deficiencies. Hohenheim Consensus Conference.
AB  - OBJECTIVE: The aim of this study was to consider the risk of micronutrient
      deficiencies and approaches for intervention, and to summarize existing knowledge
      and identify areas of ignorance. DESIGN: Experts from a range of relevant
      disciplines received and considered a series of questions related to aspects of
      the topic. INTERVENTION: The experts met and discussed the questions and arrived
      at a consensus. CONCLUSION: Though healthy balanced diet is available for the
      general European population, a few defined groups are at risk of micronutrient
      deficiencies. In addition, the intake of specific micronutrients such as iron,
      folic acid, vitamin D and vitamin B12 are often marginal. To overcome these
      deficiencies, either selected micronutrients or a mixture of different
      micronutrients might be recommended. However, to define and detect micronutrient
      deficiencies, specific biomarkers are only available for a few micronutrients (e.
      g. vitamin D, folic acid, vitamin C, iron). The definition of a risk group, based
      on scientific data, might be an appropriate way to justify intervention with
      supplements.

PMID- 14673614
TI  - Increased levels of circulating adhesion molecules in neonates with congenital
      diaphragmatic hernia complicated by persistent pulmonary hypertension.
AB  - The aim of this study was to determine circulating levels of adhesion molecules
      in serum from patients with congenital diaphragmatic hernia (CDH) to investigate
      the relationship between soluble ICAM-1, ELAM-1, and VCAM-1 liberated by
      activated vascular endothelium and the development of persistent pulmonary
      hypertension (PPH) in patients with CDH. We measured serum levels of ICAM-1, ELAM
      1, and VCAM-1 in 20 high-risk neonates with CDH at the time of diagnosis (11 with
      PPH and 9 without PPH) and 7 age-matched controls using ELISA system. We further
      examined the lungs of 5 patients with CDH complicated by PPH who died during
      resuscitation and stabilization, and three control lung specimens for the
      expression of adhesion molecules using immunohistochemistry. The mean serum ICAM
      1 levels in CDH patients with PPH (227.0+/-98.9 ng/ml) were increased compared
      with levels in CDH patients without PPH (140.29+/-37.4 ng/ml; p<0.05) and
      controls (130.0+/-23.8 ng/ml; p<0.05). Mean serum ELAM-1 levels in CDH patients
      with PPH (116.5+/-19.2 ng/ml) were significantly increased compared with levels
      in CDH patients without PPH (79.3+/-27.9 ng/ml; p<0.01) and controls (58.4+/-14.5
      ng/ml; p<0.001). Mean serum VCAM-1 levels in CDH patients with PPH (1596.9+/
      460.4 ng/ml) were significantly higher compared with levels in CDH patients
      without PPH (1069.3+/-444.6 ng/ml; p<0.01) and controls (838.0+/-171.2 ng/ml;
      p<0.001). But serum adhesion molecule levels in CDH patients without PPH were no
      different from controls statistically. Pulmonary vascular endothelial cells from
      CDH lung with PPH had strong expression of adhesion molecules compared with
      controls. Up-regulated expression of adhesion molecules on the endothelium of
      pulmonary vessels and high circulating levels of adhesion molecules in CDH
      patients with PPH suggest that adhesion molecules may play a role in the
      development of PPH in CDH.

PMID- 14673615
TI  - Scimitar syndrome treated with pneumonectomy: a case associated with
      bronchospastic attack.
AB  - Scimitar syndrome, which involves total or partial anomalous venous drainage of
      the right lung to the inferior vena cava, is relatively rare and often results in
      pulmonary hypertension, heart failure and right lung infection. We report here
      the case of a 1-year-old girl who suffered repeated attacks of bronchospasm after
      developing pneumonia. She underwent resection of the hypoplastic right lung and
      showed rapid recovery.

PMID- 14673616
TI  - Lifestyle issues and genitourinary tumours.
AB  - A variety of lifestyle factors, including physical activity, artificial
      sweeteners, alcohol consumption and smoking, have been reported to contribute to
      the risk of developing urological malignancies. A great number of epidemiological
      studies suggest that sports and physical activity may have a preventive influence
      on genitourinary tumours, especially on the incidence of prostate cancer. Smoking
      appears to be the most relevant lifestyle factor significantly increasing both
      incidence and mortality from bladder cancer. Furthermore, there is evidence
      implicating an association between tobacco use and kidney cancer. In contrast,
      prostate and testicular cancers are unlikely to be linked to tobacco use. As far
      as alcohol is concerned, most studies indicate that neither amount nor type of
      alcohol seems to be clearly associated with a risk of developing urological
      malignancies. However, some more recent cohort studies suggest a moderately
      increased risk for prostate and bladder cancer for specific types of alcohol. On
      the other hand, there is evidence that moderate alcohol consumption may even
      protect women from developing renal cancer. Since the introduction of artificial
      sweeteners, reports of potential cancer risks have circulated periodically
      through the mass media. The wide distribution of these agents and the fact that
      mostly combinations of the different compounds are added to a broad variety of
      food, drinks, drugs, and hygiene products complicates a systematic analysis of
      their potential impact on the development of urological malignancies.
      Nevertheless, so far not a single study has convincingly demonstrated a
      statistically significant risk of bladder cancer due to the consumption of
      artificial sweeteners. This survey demonstrates that the individual assessment of
      lifestyle factors not only may identify groups with an increased risk for
      urological malignancies but also clearly displays a potential for tumour
      prevention.

PMID- 14673617
TI  - Investigation of the effect of GaAs laser therapy on cervical myofascial pain
      syndrome.
AB  - Low-energy laser therapy has been applied in several rheumatoid and soft tissue
      disorders with varying rates of success. The objective of our study was to
      investigate the effect of laser therapy on cervical myofascial pain syndrome with
      a placebo-controlled double-blind prospective study model. It was performed with
      a total of 53 patients (35 females and 18 males) with cervical myofascial pain
      syndrome. In group 1 (n = 23), GaAs laser treatment was applied over three
      trigger points bilaterally and also one point in the taut bands in trapezius
      muscle bilaterally with a frequency of 1000 Hz for 2 min over each point once a
      day for 10 days during a period of 2 weeks. In group 2 (n = 25), the same
      treatment protocol was given, but the laser instrument was switched off during
      applications. All patients in both groups were instructed to perform daily
      isometric exercises and stretching just short of pain for 2 weeks at home.
      Evaluations were performed just before treatment (week 0), immediately after
      (week 2), and 12 weeks later (week 14). Evaluation parameters included pain,
      algometric measurements, and cervical lateral flexion. Statistical analysis was
      done on data collected from three evaluation stages. The results were evaluated
      in 48 patients (32 females, 16 males). Week 2 and week 14 results showed
      significant improvement in all parameters for both groups. However, comparison of
      the percentage changes both immediately and 12 weeks after treatment did not show
      a significant difference relative to pretreatment values. In conclusion, the
      results of our study have not shown the superiority of GaAs laser therapy over
      placebo in the treatment of cervical myofascial pain syndrome, but we suggest
      that further studies on this topic be done using different laser types and
      dosages in larger patient populations.

PMID- 14673618
TI  - Radon therapy for the treatment of rheumatic diseases--review and meta-analysis
      of controlled clinical trials.
AB  - OBJECTIVE: The aim of this study was to analyze the effect of radon therapy on
      pain in rheumatic diseases. METHODS: MEDLINE and MedKur databases were searched
      for the terms radon plus therapy, rheum, arthritis, and osteo. Radon therapy
      centers and experts in the field were contacted, proceedings hand-searched, and
      bibliographies checked for references of potential importance. Included were all
      prospective randomized controlled clinical trials that compared clinical effects
      of radon therapy with other interventions in patients with rheumatic diseases and
      studied pain intensity. Information concerning patients, interventions, results,
      and methodology were extracted in a standardized manner by all authors
      independently and summarized descriptively. Reports on pain reduction were pooled
      for meta-analysis. RESULTS: Five clinical trials with a total of 338 patients and
      comparing the effect on pain of radon baths (three trials) or radon speleotherapy
      (two trials) with control intervention in degenerative spinal disease (two
      trials), rheumatoid arthritis (one trial) and ankylosing spondylitis (two trials)
      met the inclusion criteria. In meta-analysis, the pooled data showed no
      difference immediately after treatment (P=0.13) but significantly better pain
      reduction in the radon group than the control group at 3 months (P=0.02) and 6
      months (P=0.002) after treatment. CONCLUSIONS: The existing trials suggest a
      positive effect of radon therapy on pain in rheumatic diseases. With respect to
      the potential clinical effect and given the increasing public interest in radon
      therapy, there is an urgent need for further randomized controlled clinical
      investigations with long-term follow-up.

PMID- 14673619
TI  - Systemic and tumor disposition of platinum after administration of cisplatin or
      STEALTH liposomal-cisplatin formulations (SPI-077 and SPI-077 B103) in a
      preclinical tumor model of melanoma.
AB  - PURPOSE: SPI-077 and SPI-077 B103 are formulations of cisplatin encapsulated in
      pegylated STEALTH liposomes that accumulate in tumors. However, the extent to
      which active platinum (Pt) is released from the liposome is unknown. Thus, we
      evaluated the disposition of encapsulated and released Pt in plasma and tumors
      after administration of STEALTH liposomal and nonliposomal cisplatin. METHODS:
      Cisplatin (10 mg/kg), SPI-077 (10 mg/kg), and SPI-077 B103 (5 mg/kg) were
      administered i.v. to mice bearing B16 murine melanoma tumors. Microdialysis
      probes were placed into the right and left sides of each tumor, and serial
      samples were collected from tumor extracellular fluid (ECF) after administration
      of each agent. After each microdialysis procedure, tumor samples were obtained at
      each probe site to measure total Pt and Pt-DNA adducts. In a separate study,
      serial plasma samples (three mice per time point) were obtained. Unbound Pt in
      tumor ECF and plasma, and total Pt in tumor homogenates were measured by
      flameless atomic absorption spectrophotometry. Area under the tumor ECF
      (AUC(ECF)) concentration versus time curves of unbound Pt were calculated.
      Intrastrand GG (Pt-GG) and AG (Pt-AG) Pt-DNA adducts were measured via (32)P
      postlabeling. RESULTS: Mean+/-SD peak concentrations of total Pt in tumor
      homogenates after administration of cisplatin, SPI-077, and SPI-077 B-103 were
      3.2+/-1.9, 11.9+/-3.0, and 3.5+/-0.3 microg/g, respectively. After cisplatin,
      mean+/-SD AUC(ECF) of unbound Pt was 0.72+/-0.46 microg/ml.h. There was no
      detectable unbound Pt in tumor ECF after SPI-077 or SPI-077 B-103 treatment.
      Mean+/-SD peak concentration of Pt-GG DNA adducts after administration of
      cisplatin, SPI-077, and SPI-077 B-103 were 13.1+/-3.3, 3.5+/-1.3, and 2.1+/-0.3
      fmol Pt/microg DNA, respectively. CONCLUSION: This study suggests that more SPI
      077 and SPI-077 B103 distribute into tumors, but release less Pt into tumor ECF,
      and form fewer Pt-DNA adducts than does cisplatin.

PMID- 14673623
TI  - CNS blast crisis of chronic myelogenous leukemia in a patient with a major
      cytogenetic response in bone marrow associated with low levels of imatinib
      mesylate and its N-desmethylated metabolite in cerebral spinal fluid.
AB  - Imatinib mesylate (STI571) is a very effective treatment option for Ph(+) chronic
      myeloid leukemia (CML) in chronic phase. Secondary treatment failures have mostly
      been observed in patients with advanced stages of disease. We report the case of
      a patient who unexpectedly experienced blast crisis of the central nervous system
      although having achieved complete cytogenetic remission in the bone marrow. The
      levels of STI571 and its metabolite N-desmethyl STI were 40-fold lower in the
      cerebral spine fluid than in plasma. The risk of CNS disease has to be kept in
      mind when patients with CML in chronic phase who are at an increased risk for
      blastic transformation are treated with imatinib mesylate.

PMID- 14673624
TI  - Assessment of mastoid air cell size versus sigmoid sinus variables with a
      tomography-assisted digital image processing program and morphometry.
AB  - We assessed the mastoid air cell size and variables of the sigmoid sinus in
      healthy ears and ears with chronic otitis media (COM). Thirty-eight patients with
      unilateral COM [15 with cholesteatoma (COM/+) and 23 without cholesteatoma (COM/
      )], and 20 subjects with healthy ears, were included in the study. Assessment was
      performed using a quantitative digital image processing computed tomography (CT)
      program, and the volume of the mastoid bone was measured using the morphometric
      method of Cavalieri. In both COM/+ and COM/- patients the sigmoid to suprameatal
      spine distance and mastoid size were greater on the healthy side than on the
      diseased side ( p<0.05). The distance and area were significantly greater in the
      healthy control subjects than in either the healthy or the diseased ears of the
      patients with COM ( p<0.05). In the healthy ears of COM patients, there was
      significant correlation between the sigmoid to suprameatal spine distance and air
      cell size and mastoid volume ( p<0.05). In the diseased ears of COM patients,
      this correlation was absent ( p>0.05). The sigmoid sinus shape was of the half
      moon type (62%), protrusive type (22%) and saucer type (16%). The digital image
      processing CT program allowed us to estimate the individual area of the air and
      soft tissue filled mastoid air cells. The mastoid size in both intact and disease
      ears of COM patients was smaller than in the healthy controls. The mastoid size
      may be determined genetically. However, environmental factors such as infection
      may also affect the mastoid size. Therefore, both genetic and environmental
      factors may be related to COM as far as the size of the mastoid air cells is
      concerned.

PMID- 14673626
TI  - Factors involved in gastrointestinal bleeding in advanced cancer patients
      followed at home.
AB  - There is a lack of information on the frequency of symptomatic gastrointestinal
      bleeding in patients with advanced cancer. This group of patients presents
      several risk factors for developing gastrointestinal bleeding. The aim of this
      multicenter longitudinal survey was to assess the frequency of gastrointestinal
      bleeding and possible factors implicated in advanced cancer patients followed at
      home. A consecutive sample of 439 patients who referred to home palliative care
      program entered the study. Age, gender, primary cancer and known metastases,
      possible associated pathologies, history of peptic disease, use of previous or
      actual nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids, drugs used to
      prevent gastric complications, the occurrence of hematemesis or melena,
      significant anemia requiring blood transfusion, and mortality associated with the
      hemorrhagic event were recorded. Of 377 patients who completed the study, 18
      reported gastrointestinal bleeding, and five had significant anemia requiring
      blood transfusion in three cases. Death was found to be related to bleeding in
      three patients. NSAIDs, steroids, and gastroprotectors were frequently used,
      either before or during home care. However, no clear relationship between age,
      gender, and the use of offender drugs with gastrointestinal bleeding was found.
      Liver involvement was frequently associated with the risk of developing
      gastrointestinal bleeding.

PMID- 14673627
TI  - [Re: Peter Blower's recent review of granisetron].

PMID- 14673629
TI  - Proteinuria as a predictor of disease progression in children with hypodysplastic
      nephropathy. Data from the Ital Kid Project.
AB  - Little is known about the role of proteinuria in the progression of childhood
      renal diseases. We analyzed the decline in creatinine clearance ( C(Cr)) and
      kidney survival in 225 children (185 males) with chronic renal failure (CRF) due
      to isolated hypodysplasia or hypodysplasia associated with urological
      abnormalities. The data were based on the information available in the Italian
      Pediatric Registry of CRF (ItalKid Project), which includes patients from all of
      Italy aged <20 years with C(Cr )levels of <75 ml/min per 1.73 m(2). Patients aged
      <2 years and those with C(Cr )levels of <20 ml/min per 1.73 m(2) or a follow-up
      of <1 year were excluded from the analysis, as were those receiving angiotensin
      converting enzyme inhibitors. At baseline, the patients had a mean age of 7.8+/
      4.2 years, a mean C(Cr )of 50+/-16.3 ml/min per 1.73 m(2), a median urinary
      protein/urinary creatinine (uPr/uCr) ratio of 0.38 (range 0.02-7.21), and a mean
      duration of follow-up of 3.5+/-1.1 years. The patients were divided into three
      groups on the basis of their baseline proteinuria levels: group A normal (uPr/uCr
      <0.2) n=83; group B low (uPr/uCr 0.2-0.9) n=71; and group C mild (uPr/uCr >0.9)
      n=71. Patients in groups A and B showed a significantly slower decline in C(Cr
      )than those in group C (slope +0.16+/-3.64 and -0.54+/-3.67 vs. -3.61+/-5.47,
      P<0.0001) and a higher rate of kidney survival after 5 years (96.7% and 94.1% vs.
      44.9%, P<0.01). By multivariate analysis, the baseline uPr/uCr ratio ( P<0.01)
      and age ( P<0.0001) correlated with a faster decline in C(Cr )irrespective of
      baseline C(Cr). There was no correlation with mean arterial blood pressure. We
      conclude that proteinuria is an independent predictor of progression to end-stage
      renal failure also in children whose renal impairment is due to congenital
      hypodysplasia.

PMID- 14673630
TI  - ACE inhibition in the treatment of children after renal transplantation.
AB  - Currently, there are no data available on long-term effects of angiotensin
      converting enzyme inhibitors (ACE-I) on graft function in children after renal
      transplantation. We therefore analyzed all children who were transplanted at our
      institution between 1989 and 1998 and followed for at least 2 years. Those
      treated with ACE-I, mainly because of failure of other antihypertensive
      medications, were compared to those without ACE-I. The ACE-I-treated children (
      n=19) showed significantly better blood pressure control during the 1st year of
      follow-up ( p<0.05). In children with chronic allograft dysfunction ( n=8),
      treatment with ACE-I stabilized graft function, with improvement in creatinine
      clearance in 50% ( p<0.01). Serum potassium and hemoglobin levels remained
      stable. One patient discontinued ACE-I because of renal artery stenosis. Taken
      together, ACE-I were effective and safe in the treatment of hypertension in
      children following renal transplantation. Children with chronic allograft
      dysfunction experienced a stabilizing effect on graft function.

PMID- 14673631
TI  - Nephrolithiasis in a child with glucose-galactose malabsorption.
AB  - Glucose-galactose malabsorption (GGM) is a rare autosomal recessive disorder of
      intestinal transport of glucose and galactose, leading to watery diarrhea,
      dehydration, failure to thrive, or early death. We report a female newborn with
      GGM, whose clinical diagnosis was confirmed by mutational analysis of the SGTL1
      gene. Bilateral nephrolithiasis was discovered after an episode of hematuria.
      Metabolic causes of nephrolithiasis were not found. The most likely explanation
      for the development of nephrolithiasis is chronic diarrhea leading to dehydration
      and highly concentrated urine. High fluid intake and rigorous prevention of
      dehydration is therefore advised for these patients. Furthermore, life-long
      monitoring of their renal status, including regular ultrasound examinations, is
      warranted.

PMID- 14673632
TI  - Collection under paraffin is not necessary for stability of urine pH over 24 h.
AB  - Collection of urine under paraffin is routinely used in clinical practice for
      urine pH evaluation. To examine whether the accuracy of pH measurement is
      adversely influenced by the method of collection and storage, we divided each
      urine specimen and sent one aliquot to the laboratory under paraffin and another
      in a sealed 5-ml plastic syringe. In another experiment we evaluated the
      stability of urine pH measurement in a clinical setting. Urine collected under
      paraffin was tested immediately for pH; an aliquot from the same specimen was
      stored in a capped 5-ml syringe at 4 degrees C and tested after 24 h. We found no
      appreciable difference in measured pH between samples sent to the laboratory
      under paraffin or in a capped plastic syringe.

PMID- 14673633
TI  - New perspectives in treatment of glomerulonephritis.
AB  - In chronic glomerulonephritis (GN) the development of the tissue damage and
      progression to fibrosis is related to the individual immune response which brings
      about excessive inflammation, failure to activate regression and glomerular
      repair and excessive fibrogenic activity. Therefore, the present standard
      treatment of GN has two aims, to fight the acute inflammation and to inhibit the
      progressive renal fibrosis. New avenues in the anti-inflammatory and
      immunosuppressive treatment of the active phase of glomerular diseases include
      the use of drugs proven to be of value in organ transplantation (mycophenolate
      mofetil, rapamycin or anti-immune adhesion and anti-co-stimulatory molecules).
      Interest has recently focused on anti-inflammatory cytokines (monoclonal
      antibodies, peptidic antagonists or anti-sense oligonucleotides against TNF
      alpha, anti-PDGF-beta, anti-TGF-beta and cytokine receptor antagonists) and anti
      inflammatory natural cytokines (such as IL4, IL10, IL13 or low doses of TGFbeta).
      Other drugs may act by depleting B cells (such as anti-CD20 monoclonal antibody)
      or on several immune pathways, such as thalidomide or anti-cyclooxygenase 2.
      Several anti-sclerogenic drugs are already used for treatment of the chronic
      phase of glomerular diseases, such as antagonists of angiotensin II, statins and
      antioxidants. Other drugs are still experimental, including endothelin receptor
      antagonists and neutral endopeptidase or vasopeptidase inhibitors and other drugs
      operating on extracellular matrix accumulation/degradation mechanisms, e.g.,
      pirfenidone. There are extremely interesting developments concerning activators
      of endogenous anti-inflammatory mechanisms, such as those regulated by peroxisome
      proliferator activated receptors. There is a need for successful treatment of
      chronic GN in childhood. This short review of the most promising new drugs shows
      there is reason to believe that the next decade will provide exciting new tools
      for the treatment of these diseases in children.

PMID- 14673634
TI  - Dynamic (re)organization of the podocyte actin cytoskeleton in the nephrotic
      syndrome.
AB  - The visceral glomerular epithelial cell, also known as the podocyte, plays an
      important role in the maintenance of renal glomerular function. This cell type is
      highly specialized and its foot processes together with the interposed slit
      diaphragm (SD) form the final barrier to urinary protein loss. Effacement of foot
      processes is associated with the development of proteinuria and-if not reversed
      in a certain time-with permanent deterioration of the glomerular filter. To
      maintain an intact glomerular filter barrier, podocyte-podocyte interactions and
      podocyte interactions with the glomerular basement membrane (GBM) are essential.
      Recent years have highlighted podocyte functions by unraveling the molecular
      composition of the SD, but have also clarified the important role of the podocyte
      actin cytoskeleton, and the podocyte-GBM interaction in the development of foot
      process (FP) effacement. This review provides an update of podocyte functions
      with respect to novel podocyte-specific proteins and also focuses on the dynamic
      interaction between the actin cytoskeleton of podocytes, their cell surface
      receptors and the GBM.

PMID- 14673635
TI  - Genetic determination of nephrogenesis: the Pax/Eya/Six gene network.
AB  - Development of the kidney serves as a paradigm to understand the mechanisms
      underlying the formation of an organ. The first sign of kidney development is the
      interaction between two tissues derived from the intermediate mesoderm, the
      metanephrogenic mesenchyme and the nephric duct. Many of the genes that play a
      crucial role in early kidney development, such as Pax2, Eya1, Six1, Six2, Sall1,
      Foxc1, Wt1, and the Hox11 genes, are expressed in the mesenchyme and encode
      transcription factors that--with few exceptions--are involved in regulation of
      the Gdnf gene. Moreover, mutations in a number of these genes in humans are
      associated with kidney diseases. Interestingly, many of the components regulating
      early kidney development are conserved throughout evolution and are also involved
      in eye and muscle formation in mammals, as well as in eye development in
      Drosophila. Genetic and biochemical studies in Drosophila and mice indicate that
      these genes and their respective products act in a complex network of
      interdependencies and positive and negative feedback loops. Genetic experiments
      have allowed us to begin to characterize the complex interactions between the
      individual components, but it will require additional biochemical and functional
      experiments to eventually understand the molecular functions of each of the
      participating proteins.

PMID- 14673636
TI  - Adequacy of dialysis in children: does small solute clearance really matter?
AB  - Measurement of dialysis adequacy relies on an assessment of small molecule
      clearance during the dialysis procedure. However, recent adult studies (HEMO and
      ADEMEX) that pushed clearance to maximally achievable levels within practical
      constraints of thrice-weekly hemodialysis or four times daily continuous
      ambulatory peritoneal dialysis failed to demonstrate improvements in patient
      outcome above current guidelines. The relatively low incidence of pediatric
      compared with adult end-stage renal disease limits large-scale study of pediatric
      dialysis. Several single-center pediatric studies demonstrate a lack of
      association between small solute clearance alone and patient growth. The aim of
      the current article is to review the relevant pediatric and adult studies of
      small solute clearance and put them in the context of optimal dialysis provision.
      While small solute clearances do indeed matter, clearance is not all that
      matters. Our quest to provide optimal dialysis requires that we also focus our
      attention on patient nutritional status, increased dialysis delivery
      (daily/nocturnal hemodialysis), and adjunctive dialysis modalities
      (hemofiltration and renal tubular replacement therapy).

PMID- 14673637
TI  - Predator induced phenotypic plasticity in the pinewoods tree frog, Hyla
      femoralis: necessary cues and the cost of development.
AB  - Predator-induced defenses can result from non-contact cues associated with the
      presence of a feeding predator; however, the nature of the predator cue has not
      been determined. We tested the role of two non-contact cues, metabolites of
      digestion of conspecific prey released by the predator and alarm pheromones
      released by attacked conspecific prey, in the development of inducible defenses
      by exposing pinewoods tree frog (Hyla femoralis) tadpoles to non-lethal dragonfly
      (Anax junius) larvae fed either inside experimental bins or removed from the bins
      for feeding to eliminate alarm pheromones. The costs associated with the
      development of the induced morphology were also investigated by providing the
      tadpoles with two food levels intended to provide adequate or growth limiting
      resources. The generalized morphological response of H. femoralis tadpoles to
      predators included the development of bodies and tails that were both deeper and
      shorter, smaller overall body size, and increased orange tail fin coloration and
      black tail outline. Metabolites of digestion were sufficient to initiate
      development of inducible defenses; however, the combination of metabolites and
      alarm cue resulted in a greater response. Furthermore, growth and development
      were slowed in tadpoles that expressed the induced morphology; however, this
      growth cost was insufficient to preclude the development of the induced
      morphology when food resources were low. These results indicate that two aspects
      of the indirect predator cue work together to trigger a morphological anti
      predator response.

PMID- 14673638
TI  - Forest edges and fire ants alter the seed shadow of an ant-dispersed plant.
AB  - Exotic species invade fragmented, edge-rich habitats readily, yet the distinct
      impacts of habitat edges and invaders on native biota are rarely distinguished.
      Both appear detrimental to ant-dispersed plants such as bloodroot, Sanguinaria
      canadensis. Working in northeastern Georgia (USA), an area characterized by a
      rich ant-dispersed flora, fragmented forests, and invasions by the red imported
      fire ant, Solenopsis invicta, I monitored the interactions between ants and S.
      canadensis seeds in uninvaded forest interiors, uninvaded forest edges, invaded
      forest interiors, and invaded forest edges. I observed 95% of the seed dispersal
      events that occurred within the 60-min observation intervals. Seed collection
      rates were similar among all four (habitat x invasion) groups. The presence of
      invasive ants had a strong effect on seed dispersal distance: S. invicta
      collected most seeds in invaded sites, but was a poorer disperser than four of
      five native ant taxa. Habitat type (interior versus edge) had no effect on seed
      dispersal distance, but it had a strong effect on seed dispersal direction.
      Dispersal towards the edge was disproportionately rare in uninvaded forest edges,
      and ants in those habitats moved the average dispersed seed approximately 70 cm
      away from that edge. Dispersal direction was also skewed away from the edge in
      uninvaded forest interiors and invaded forest edges, albeit non-significantly.
      This biased dispersal may help explain the rarity of myrmecochorous plants in
      younger forests and edges, and their poor ability to disperse between fragments.
      This is the first demonstration that forest edges and S. invicta invasion
      influence seed dispersal destination and distance, respectively. These forces act
      independently.

PMID- 14673639
TI  - Consumption of salmon by Alaskan brown bears: a trade-off between nutritional
      requirements and the risk of infanticide?
AB  - The risk of infanticide may alter foraging decisions made by females, which
      otherwise would have been based on nutritional requirements and forage quality
      and availability. In systems where meat resources are spatially aggregated in
      late summer and fall, female brown bears (Ursus arctos) would be faced with a
      trade-off situation. The need of reproductive females to accumulate adequate fat
      stores would likely result in a decision to frequent salmon streams and consume
      the protein- and lipid-rich spawning salmon. In contrast, aggregations of bears
      along salmon streams would create conditions of high risk of infanticide. We
      investigated consumption of salmon by brown bears on Admiralty and Chichagof
      Islands in Southeast Alaska from 1982 to 2000 using stable isotope analysis and
      radiotelemetry. While nearly all males (22 of 23) consumed relatively large
      amounts of salmon (i.e., >10% relative contribution to seasonal diet), not all
      females (n=56) did so. Five of 26 females for which we had reproductive data,
      occupied home ranges that had no access to salmon and thus did not consume salmon
      when they were mated or accompanied by young. Of females that had access to
      salmon streams (n=21), all mated individuals (n=16) had delta(15)N values
      indicative of salmon consumption. In contrast, 4 out of 16 females with cubs
      avoided consuming salmon altogether, and of the other 12, 3 consumed less salmon
      than they did when they were mated. For 11 of 21 females with access to salmon
      streams we had data encompassing both reproductive states. Five of those altered
      foraging strategies and exhibited significantly lower values of delta(15)N when
      accompanied by young than when mated, while 6 did not. Radiotelemetry data
      indicated that females with spring cubs were found, on average, further away from
      streams during the spawning season compared with females with no young, but both
      did not differ from males and females with yearlings and 2-year-olds. Females
      with young that avoided salmon streams were significantly lighter indicating that
      female choice to avoid consumption of salmon carries a cost that may translate to
      lower female or cub survivorship. The role of the social hierarchy of males and
      females, mating history, and paternity in affecting the risk of infanticide and
      foraging decisions of female brown bears merit further investigation.

PMID- 14673640
TI  - Estimating scale-dependency in disturbance impacts: El Ninos and giant kelp
      forests in the northeast Pacific.
AB  - Recent discussions on scaling issues in ecology have emphasized that processes
      acting at a wide range of spatial and temporal scales influence ecosystems and
      thus there is no appropriate single scale at which ecological processes should be
      studied. This may be particularly true for environmental disturbances (e.g. El
      Nino) that occur over large geographic areas and encompass a wide range of scales
      relevant to ecosystem function. However, it may be possible to identify the
      scale(s) at which ecosystems are most strongly impacted by disturbances, and thus
      provide a measure by which their impacts can be most clearly described, by
      assessing scale-dependent changes in the patterns of variability in species
      abundance and distribution. This, in turn, may yield significant insight into the
      relative importance of the various forcing factors responsible for generating
      these impacts. The 1997-98 El Nino was one of the strongest El Ninos ever
      recorded. I examined how this event impacted giant kelp populations in the
      northeast Pacific Ocean at 90 sites ranging from central Baja California, Mexico
      to central California, USA. These sites spanned the geographic range of giant
      kelp in the Northeast Pacific and were surveyed just before, immediately
      following, several months after, more than 1 year after, and nearly 2 years after
      the El Nino. I used a hierarchical sample design to compare these impacts at five
      spatial scales spanning six orders of magnitude, from a few meters to more than
      1,000 km. Variance Components Analyses revealed that the El Nino shifted control
      over giant kelp abundance from factors acting at the scale of a few meters (local
      control) to factors operating over hundreds to thousands of kilometers (regional
      control). Moreover, El Nino resulted in the near-complete loss of all giant kelp
      throughout one-half of the species' range in the northeast Pacific Ocean. Giant
      kelp recovery following El Nino was far more complex and variable at multiple
      spatial scales, presumably driven by numerous factors acting at those scales.
      Recovery returned local control of giant kelp populations within 6 months in
      southern California, and within 2 years in Baja California.

PMID- 14673641
TI  - The effect of mechanical load on integrin subunits alpha5 and beta1 in
      chondrocytes from mature and immature cartilage explants.
AB  - Articular cartilage is subjected to cyclic compressive stresses during joint
      loading. There is increasing experimental evidence that this loading is essential
      for the chondrocytes to maintain the functionality of the cartilage extracellular
      matrix (ECM) and that members of the integrin family of transmembrane receptors
      may play an important role in signal mechanotransduction between the ECM and
      chondrocytes. Of particular interest are the integrin subunits alpha5 and beta1,
      which are known to form the receptor for fibronectin, an important ECM protein,
      and to be involved in mechanotransduction as well as in the regulation of
      cytokine production. In this study, we measured the amounts of the integrin
      subunits alpha5 and beta1 in chondrocytes from young (immature) and adult
      (mature) bovine articular cartilage explants which were subjected to a
      continuously applied cyclic compressive stress of 1 MPa for 6 and 24 h. The
      integrin content per chondrocyte was measured immediately after load cessation by
      flow cytometry following matrix digestion to release the cells. We found that a
      mechanical stress induced an increase in the number of integrin subunit alpha5 in
      immature and mature cartilage but not in the integrin subunit beta1 content. The
      integrin contents were greatest after 6 h of loading and returned to control
      levels after 24 h of unloading. The results of this study supply further
      experimental evidence that chondrocytes respond to changes in their mechanical
      environment and that the integrin alpha5beta1 may act as a mechanical signal
      transducer between the chondrocyte and the ECM for the modulation of cellular
      physiology.

PMID- 14673642
TI  - Reduction of alkaline phosphatase activity in aged human osteogenic periodontal
      ligament fibroblasts exhibiting short telomeres.
AB  - The osteogenic cell type of human periodontal ligament fibroblasts (PDLF)
      undergoes senescence at finite population doubling numbers unrelated to donor
      ages. This study investigated telomere lengths of osteogenic PDLF from
      differently aged donors and alterations of the osteoblast-like properties in the
      aged PDLF with short telomeres. Telomere lengths of osteogenic PDLF were biased
      towards long or short among all 15- to 51-year-old individuals, and did not show
      a normal distribution by Pearson's test or a correlation to donor age by simple
      regression analysis. In osteogenic PDLF, senescence-associated beta-galactosidase
      was expressed in 78.5% of cells in the clones with short telomeres (mean 3.02
      kbp), and in 9.4% of cells in the clones with long telomeres (mean 13.06 kbp).
      These results suggest that human periodontium comprises aged osteogenic PDLF
      without correlation to age. Osteogenic PDLF with long telomeres strongly
      expressed alkaline phosphatase (ALPase) activity whereas cells with short
      telomeres expressed ALPase activity to a weaker extent. Total activity of ALPase
      in the clones of osteogenic PDLF with long telomeres was significantly higher
      than that in the clones with short telomeres. The produced amounts of both
      osteopontin and osteocalcin in the clones of osteogenic PDLF with long telomeres
      were slightly but statistically significantly smaller than those in the clones
      with short telomeres. These findings suggest that aged osteogenic PDLF reduce the
      expression of ALPase activity but that there is not a critical alteration in bone
      associated protein production. Aged osteogenic PDLF may impair the ability to
      induce ALPase-dependent calcification.

PMID- 14673643
TI  - Single cell co-amplification of polymorphic markers for the indirect
      preimplantation genetic diagnosis of hemophilia A, X-linked adrenoleukodystrophy,
      X-linked hydrocephalus and incontinentia pigmenti loci on Xq28.
AB  - Preimplantation genetic diagnosis (PGD) first consisted of the selection of
      female embryos for patients at risk of transmitting X-linked recessive diseases.
      Advances in molecular biology now allow the specific diagnosis of almost any
      Mendelian disease. For families with an identified X-linked recessive disease
      causing mutation, non-specific diagnosis by sex identification can be considered
      as a sub-standard method, since it involves the unnecessary disposal of healthy
      male embryos and reduces success rate by diminishing the pool of embryos eligible
      for transfer. The most telomeric part of the X-chromosome long arm is a highly
      gene-rich region encompassing disease genes such as haemophilia A, X-linked
      adrenoleukodystrophy, X-linked hydrocephalus and incontinentia pigmenti. We
      developed five single-cell triplex amplification protocols with microsatellite
      markers DXS1073, DXS9901 (BGN), G6PD, DXS1108, DXS8087 and F8C-IVS13 located in
      this Xq terminal region. These tests allow the diagnosis of all diseases
      previously mentioned providing that the genetic material allowing the
      identification of the morbid allele can be obtained. The choice of the
      microsatellite set to use depends on the localisation of the gene responsible for
      the diagnosed pathology and on the informativity of the markers in particular
      families. Single-cell amplification efficiency was assessed on single
      lymphocytes. Amplification rate of the different markers ranged from 89-97% with
      an allele drop out rate of 2-19%. So far PGD has been carried out for three
      carrier females at risk of transmitting X-linked adrenoleukodystrophy, X-linked
      hydrocephalus and hemophilia A. The latter one is now pregnant.

PMID- 14673644
TI  - Localized aggressive periodontitis is linked to human chromosome 1q25.
AB  - Localized aggressive periodontitis (LAP; previously known as localized juvenile
      periodontitis) is one of the rapidly progressive periodontal diseases. Certain
      forms of familial LAP show a simple Mendelian pattern of transmission. However,
      no gene mutation has been identified to be responsible for the LAP phenotype. As
      an initial step to identify a gene mutation associated with LAP, we have
      performed genetic linkage analysis with four multigenerational families
      exhibiting the LAP phenotype. Affected individuals in the families were
      identified based on clinical and laboratory criteria in an attempt to define a
      homogeneous phenotype, since the clinical presentation of LAP may represent a
      manifestation of a heterogeneous group of diseases. The LAP phenotype is linked
      to a DNA marker, D1S492, with LOD score 3.48, theta=0.00. The haplotype analysis
      of the chromosome interval associated with D1S492 indicates that a LAP locus is
      located between D1S196 and D1S533 on chromosome 1, covering about 26 million DNA
      basepairs. We have also examined the DNA sequence of prostaglandin-endoperoxide
      synthase 2 (PTGS2 or cyclooxygenase 2, COX2) since prostaglandin 2 (PGE2), the
      product of COX2, is upregulated in LAP patients and COX2 is located between
      D1S196 and D1S533. No mutation in COX2 was identified in the patients.

PMID- 14673645
TI  - A PCR-based system for highly efficient generation of gene replacement mutants in
      Ustilago maydis.
AB  - Ustilago maydis, the causative agent of corn smut disease, is one of the most
      versatile model systems for the study of plant pathogenic fungi. With the
      availability of the complete genomic sequence there is an increasing need to
      improve techniques for the generation of deletion mutants in order to elucidate
      the functions of unknown genes. Here a method is presented which allows one to
      generate constructs for gene replacement without the need for cloning. The 5' and
      3'-regions of the target gene are first amplified by PCR, and subsequently
      ligated directionally to a marker cassette via two distinct SfiI sites, providing
      the flanking homologies needed for homologous recombination in U. maydis. Then
      the ligation product is used as a template for the amplification of the deletion
      construct, which can be used directly for transformation of U. maydis. The use of
      the fragments generated by PCR drastically increases the frequency of homologous
      recombination when compared to the linearized plasmids routinely used for gene
      replacement in U. maydis.

PMID- 14673646
TI  - The effect of drugs on cell structure of Tritrichomonas foetus.
AB  - The effects of the microtubule affecting drugs taxol, nocodazole and colchicine
      on the cell cycle and ultrastructure of Tritrichomonas foetus, a protist parasite
      of cattle, were studied. Alterations in the cytoskeleton, motility and organellar
      ultrastructure were followed using anti-tubulin antibodies and fluorescence
      microscopy, scanning- and transmission-electron microscopy. Flow cytometry was
      also used to analyze the effect of the drugs on the cell cycle. T. foetus was
      treated with 10 microM taxol, 15 microM nocodazole or 1.5 mM colchicine for 12 h.
      The first effect observed was pseudocyst formation and alterations in cell
      motility. The cell cycle was affected and the cells have blocked cytokinesis, but
      not karyokinesis. The behavior of Golgi, hydrogenosomes and vacuoles was
      analyzed. The following effects were seen following drug treatments: (1) cell
      motility was altered and flagella internalized; (2) microtubules of the pelta
      axostyle complex were not depolymerized and the axostyle assumed a curved form;
      (3) hydrogenosomes were of abnormal size and shape; (4) cells became
      multinucleate; (5) the division process was blocked in cytokinesis; (6)
      autophagic vacuoles containing a large amount of microtubules were seen; (7)
      axoneme organization was altered; (8) zoids were formed; (9) signs of cell death,
      such as membrane blebbing, were observed.

PMID- 14673647
TI  - Expression of insulin-like growth factor mitogenic signals in adult soft-tissue
      sarcomas: significant correlation with malignant potential.
AB  - The insulin-like growth factor (IGF) signal transduction system involves
      receptors, ligands and binding proteins (IGFBPs) that have been shown to have
      mitogenic and distinct anti-apoptotic effects on malignant cell lines of both
      epithelial and mesenchymal origin. Expression of the IGF signal system might be a
      mechanism by which human soft-tissue sarcomas (STS) obtain a proliferative
      advantage over normal adjacent tissues. IGFBP2, one of at least six different
      binding proteins identified to date, is secreted by most sarcoma cell lines and
      appears to be involved in cell proliferation and transformation. Circulating
      levels of this protein are markedly increased in malignancy. We have assessed 46
      adult STS specimens of low, intermediate and high pathological grade of
      malignancy for the immunohistochemical expression of IGFBP2, IGF1, IGF2, IGF1
      receptor-alpha and -beta (IGF1Ralpha/beta). The protein expression was measured
      by quantitative color video image analysis and semi-quantitative evaluation, and
      the measurements correlated well (Spearman, P<0.001). Using both methods,
      significant differences in expression of IGFBP2 among each of the three grades,
      expression of IGF2 between intermediate and high grade, and expression of
      IGF1Rbeta between low-intermediate and low-high grade were observed (Dunnett
      test, P<0.05). Multiple regression analysis for both quantitative and semi
      quantitative data confirmed the significance of the relationship and independence
      of the proteins, except IGF2. We concluded that IGFBP2 and IGF1Rbeta are
      independent predictors of the malignant potential of adult STS.

PMID- 14673648
TI  - Giant metastatic liver in a patient with small-cell neuroendocrine carcinoma of
      the lung.

PMID- 14673649
TI  - Sex determination in Drosophila melanogaster and Musca domestica converges at the
      level of the terminal regulator doublesex.
AB  - Sex-determining cascades are supposed to have evolved in a retrograde manner from
      bottom to top. Wilkins' 1995 hypothesis finds support from our comparative
      studies in Drosophila melanogaster and Musca domestica, two dipteran species that
      separated some 120 million years ago. The sex-determining cascades in these flies
      differ at the level of the primary sex-determining signal and their targets, Sxl
      in Drosophila and F in Musca. Here we present evidence that they converge at the
      level of the terminal regulator, doublesex ( dsx), which conveys the selected
      sexual fate to the differentiation genes. The dsx homologue in Musca, Md-dsx,
      encodes male-specific (MdDSX(M)) and female-specific (MdDSX(F)) protein variants
      which correspond in structure to those in Drosophila. Sex-specific regulation of
      Md-dsx is controlled by the switch gene F via a splicing mechanism that is
      similar but in some relevant aspects different from that in Drosophila. MdDSX(F)
      expression can activate the vitellogenin genes in Drosophila and Musca males, and
      MdDSX(M) expression in Drosophila females can cause male-like pigmentation of
      posterior tergites, suggesting that these Musca dsx variants are conserved not
      only in structure but also in function. Furthermore, downregulation of Md-dsx
      activity in Musca by injecting dsRNA into embryos leads to intersexual
      differentiation of the gonads. These results strongly support a role of Md-dsx as
      the final regulatory gene in the sex-determining hierarchy of the housefly.

PMID- 14673650
TI  - Evaluation of the Escherichia coli threonine deaminase gene as a selectable
      marker for plant transformation.
AB  - The initial step in the synthesis of isoleucine (Ile) is the conversion of
      threonine to alpha-ketobutyrate. This reaction is carried out by threonine
      deaminase (TD), which is feedback-regulated by Ile. Mutations in TD that manifest
      insensitivity to Ile feedback inhibition result in intracellular accumulation of
      Ile. Previous reports have shown that in planta expression of the wild-type
      Escherichia coli TD, ilvA, or an Ile-insensitive mutant designated ilvA-466,
      increased cellular concentrations of Ile. A structural analog of Ile, l-O
      methylthreonine (OMT), is able to compete effectively with Ile during translation
      and induce cell death. It has been postulated that OMT could therefore be
      utilized as an effective selective agent in plant engineering studies. To test
      this concept, we designed two binary plasmids that harbored an nptII cassette and
      either the wild-type ilvA or mutant ilvA-466. The ilvA coding sequences were
      fused to a plastid transit peptide down stream of a modified 35S CaMV promoter.
      Tobacco transformations were set up implementing a selection protocol based on
      either kanamycin or OMT. The ilvA gene was effectively utilized as a selectable
      marker gene to identify tobacco transformants when coupled with OMT as the
      selection agent. However, the transformation efficiency was substantially lower
      than that observed with nptII using kanamycin as the selection agent. Moreover,
      in a subset of the ilvA transformants and in a majority of the ilvA-466
      transgenic lines, a severe off-type was observed under greenhouse conditions that
      correlated with increased levels of expression of the ilvA transgene.

PMID- 14673651
TI  - Dichloroacetate does not speed phase-II pulmonary VO2 kinetics following the
      onset of heavy intensity cycle exercise.
AB  - We hypothesised that pharmacological activation of the pyruvate dehydrogenase
      enzyme complex (PDC) by dichloroacetate (DCA) would speed phase-II pulmonary O2
      uptake (VO2) kinetics following the onset of high-intensity, sub-maximal
      exercise. Eight healthy males (aged 19-33 years) completed two "square-wave"
      transitions of 6 min duration from unloaded cycling to a work-rate equivalent to
      approximately 80% of peak VO2 either with or without prior i.v. infusion of DCA
      (50 mg kg(-1) body mass in 50 ml saline). Pulmonary VO2 was measured breath-by
      breath throughout all tests, and VO2 kinetics were determined using non-linear
      regression techniques from the averaged individual response to each of the
      conditions. Infusion of DCA resulted in significantly lower blood [lactate]
      during the baseline cycling period (means+/-SEM: control 0.9+/-0.1, DCA 0.5+/-0.1
      mM; P<0.01) consistent with successful activation of PDC. However, DCA had no
      discernible effect on the rate at which VO2 increased towards the initially
      anticipated steady state following the onset of exercise as reflected in the time
      constant of the fundamental VO2 response (control 26.7+/-4.1, DCA 27.7+/-2.8 s).
      These results indicate that the principal limitation to oxidative metabolism
      following the onset of high-intensity, sub-maximal cycle exercise lies downstream
      from PDC and/or that muscle O2 consumption is primarily under "feedback" control
      via the concentration of one or more of the reactants associated with ATP
      hydrolysis.

PMID- 14673652
TI  - Matrix analyses of interaction among fingers in static force production tasks.
AB  - The fingers on a hand show interactions in force production tasks. The
      interfinger connection matrices (IFMs) quantify these interactions (Li et al.
      2002; Zatsiorsky et al. 2002b; Danion et al. 2003). The goal of the present study
      was to explore the differences in the IFMs of individual subjects and, in
      particular, to establish a procedure that may be used in the future for
      diagnostic purposes. Subjects ( n=20) pressed downward maximally with ten
      different combinations of the four fingers, index (I), middle (M), ring (R), and
      little (L): I, M, R, L, IM, MR, RL, IMR, MRL, and IMRL. Voluntary activation of a
      subset of the four fingers was accompanied by an involuntary force production by
      fingers that were not intentionally activated (enslaving). Interfinger connection
      matrices were computed for each subject by the artificial neural network. The
      similarities/dissimilarities (proximities) between the individual matrices were
      determined. This procedure was performed twice: (a) for nonnormalized IFMs whose
      elements represented the amount of force (in newtons) exerted by a finger i in
      response to a unit command to a finger j; and (b) for normalized IFMs, after
      dividing the elements of each IFM by the total force produced by the four fingers
      acting together (the elements of the matrix are in percents). The 20x20 matrix of
      the proximities was subjected to multidimensional scaling (MDS) to reduce the
      number of dimensions and identify the major ones. To interpret the meaning of the
      computed dimensions, they were regressed on a set of finger force parameters
      described in the text. For the nonnormalized IFMs an interpretable dimension was
      the strength of the subjects. For the normalized IFMs two dimensions were
      interpreted: (a) the location of the point of resultant force application along
      the mediolateral axis that is defined by the pattern of force sharing among the
      fingers and (b) the total contribution of the enslaved forces into the total
      finger force. We speculate that the similarity of typical everyday tasks across
      the population promotes the similarity of the IMFs reflecting optimal hand
      functioning over these tasks.

PMID- 14673653
TI  - Optical acceleration cancellation: a viable interception strategy?
AB  - Interception of fly balls requires active locomotion toward the point where
      catching can take place; as a result, the visual information guiding interception
      is affected by the catcher's own movement. The only interception theory currently
      available for a catcher standing in the plane of motion of the ball is Optical
      Acceleration Cancellation (OAC); in this strategy, the pseudo-optical variable
      "optical acceleration" (OA), if nonzero, specifies how the catcher should adjust
      his current velocity. We formulate a precise implementation of OAC where the
      catcher strives to maintain OA zero at all times and analyze its implications in
      terms of the catcher's interception behavior for different ball trajectories
      under air-friction-free, low-friction, and friction-dominated conditions. We
      conclude that the point in the ball trajectory where first visual contact (FVC)
      takes place determines to a large extent the ensuing interception behavior of the
      catcher. Conventional trajectories (FVC slightly above eye level, ball coming
      toward the catcher) result in fast acceleration to a constant velocity and
      successful interception. Trajectories with FVC below eye level typically result
      in unsatisfactory behavior of the catcher, who runs away from rather than toward
      the point of interception. In addition, ball trajectories are identified for
      which the OA equals zero even though the catcher is not on an interception
      course.

PMID- 14673654
TI  - Estimation of single-trial multicomponent ERPs: differentially variable component
      analysis (dVCA).
AB  - A Bayesian inference framework for estimating the parameters of single-trial,
      multicomponent, event-related potentials is presented. Single-trial recordings
      are modeled as the linear combination of ongoing activity and multicomponent
      waveforms that are relatively phase-locked to certain sensory or motor events.
      Each component is assumed to have a trial-invariant waveform with trial-dependent
      amplitude scaling factors and latency shifts. A Maximum a Posteriori solution of
      this model is implemented via an iterative algorithm from which the component's
      waveform, single-trial amplitude scaling factors and latency shifts are
      estimated. Multiple components can be derived from a single-channel recording
      based on their differential variability, an aspect in contrast with other
      component analysis techniques (e.g., independent component analysis) where the
      number of components estimated is equal to or smaller than the number of
      recording channels. Furthermore, we show that, by subtracting out the estimated
      single-trial components from each of the single-trial recordings, one can
      estimate the ongoing activity, thus providing additional information concerning
      task-related brain dynamics. We test this approach, which we name differentially
      variable component analysis (dVCA), on simulated data and apply it to an
      experimental dataset consisting of intracortically recorded local field
      potentials from monkeys performing a visuomotor pattern discrimination task.

PMID- 14673655
TI  - Conduction in bundles of demyelinated nerve fibers: computer simulation.
AB  - This study presents a model of action potential propagation in bundles of
      myelinated nerve fibers. The model combines the single-cable formulation of
      Goldman and Albus (1967) with a basic representation of the ephaptic interaction
      among the fibers. We analyze first the behavior of the conduction velocity (CV)
      under the change of the various conductance parameters and temperature. The main
      parameter influencing the CV is the fast sodium conductance, and the dependence
      of CV on the temperature is linear up to 30 degrees C. The increase of myelin
      thickness above its normal value (5 microm) gives a slight increase in CV. The CV
      of the single fiber decreases monotonically with the disruption of myelin, but
      the breakdown is abrupt. There is always conduction until the thickness is larger
      than 2% of its original value, at which with at this point a sharp transition of
      CV to zero occurs. Also, the increase of temperature can block conduction. At 5%
      of the original thickness there is still spike propagation, but an increase of 2
      degrees C causes conduction block. These results are consistent with clinical
      observations. Computer simulations are performed to show how the CV is affected
      by local damage to the myelin sheath, temperature alterations, and increased
      ephaptic coupling (i.e., coupling of electrical origin due to the electric
      neutrality of all the nerve) in the case of fiber bundles. The ephaptic
      interaction is included in the model. Synchronous impulse transmission and the
      formation of "condensed" pulse states are found. Electric impulses with a delay
      of 0.5 ms are presented to the system, and the numerical results show that, for
      increasing coupling, the impulses tend to adjust their speed and become
      synchronized. Other interesting phenomena are that spurious spikes are likely to
      be generated when ephaptic interaction is raised and that damaged axons suffering
      conduction block can be brought into conduction by the normal functioning fibers
      surrounding them. This is seen also in the case of a large number of fibers
      (N=500). When all the fibers are stimulated simultaneously, the conduction
      velocity is found to be strongly dependent on the level of ephaptic coupling and
      a sensible reduction is observed with respect to the propagation along an
      isolated axon even for low coupling level. As in the case of three fibers, spikes
      tend to lock and form collective impulses that propagate slowly in the nerve. On
      the other hand, if only 10% of fibers are stimulated by an external input, the
      conduction velocity is only 2% less than that along a single axon. We found a
      threshold value for the ephaptic coupling such that for lower values it is
      impossible to recruit the damaged fibers into conduction, for values of the
      coupling equal to this threshold only one fiber can be restored by the nondamaged
      fibers, and for values larger than the threshold an increasing number of fibers
      can return to normal functioning. We get values of the ephaptic coupling such
      that 25% of axons can be damaged without change of the collective conduction.

PMID- 14673656
TI  - Arsenic exposure in the wine growing industry in ten French departments.
AB  - OBJECTIVES: This study investigated exposure to arsenic, a carcinogenic fungicide
      used in wine growing. METHODS: The first phase compared urinary arsenic excretion
      of controls and workers exposed at the end of application. The second phase
      measured the increase in urinary arsenic excretion during the first day of use.
      RESULTS: A significant increase in urinary arsenic excretion was observed in
      arsenic applicators during the first phase. Urinary arsenic concentrations
      exceeded the American Conference of Governmental Industrial Hygienists (ACGIH)
      exposure index in one-third of the workers. The second phase showed a significant
      increase in urinary arsenic excretion by the first day of application. A closed
      tractor cabin provided a protective effect, but the efficacy of individual
      protection equipment was not demonstrated. CONCLUSION: This study showed the
      difficulties of achieving the effective protection of arsenic applicators and has
      led to the banning of the use of arsenic in French vineyards.

PMID- 14673657
TI  - Dual Y chromosome painting and in situ cell-specific immunofluorescence staining
      in lung tissue: an improved method of identifying donor marrow cells in lung
      following bone marrow transplantation.
AB  - Several recent studies have demonstrated localization of donor bone marrow
      derived cells in recipient lungs following transplantation from male to female
      mice or patients. Donor cells are identified by detection of the Y chromosome by
      fluorescence in situ hybridization (FISH). However, protein digestion
      pretreatments usually required for tissue FISH significantly limit the ability to
      detect cell type-specific markers by immunohistochemistry. We have used an
      alternative protein digest approach that entails heating the slides in 10 mM
      sodium citrate rather than utilizing a protease digestion. This approach
      preserves cell proteins following FISH, and allows lung tissue to remain intact
      for subsequent detection of cell-specific markers by immunohistochemistry. We
      have examined this technique in mouse lungs using a Y chromosome paint and three
      cell-specific markers, a pan-cytokeratin for epithelial cells, PECAM-1 for
      endothelial cells, and CD45 for leukocytes. Excellent visualization of both the Y
      chromosome and cell-specific surface protein markers was obtained on a single
      slide. This approach will significantly enhance the ability to detect and
      identify donor bone marrow cells in recipient mouse lungs following male to
      female transplantation.

PMID- 14673658
TI  - Direct visualization of intracellular calcium in rat osteoblasts by energy
      filtering transmission electron microscopy.
AB  - Osteoblasts are the highly specialized bone cells responsible for matrix
      mineralization. Mineralization is a complex, incompletely understood, process
      involving intracellular calcium homeostasis. Rapid changes in ionized calcium
      concentration ([Ca(2+)](i)) occur in these cells, but the intracellular
      distribution of total calcium, which may be involved in matrix mineralization,
      remains unknown. We have therefore investigated the distribution of total calcium
      in osteoblasts either ex vivo from rapidly mineralizing neonatal rat bones or in
      the same cells cultured to confluence before they had entered the mineralization
      phase, and without stimulation for mineralized matrix formation. All cells were
      examined bone-untreated (controls) or following the addition of the ionophore
      ionomycin that induced a large and sustained increase in [Ca(2+)](i).
      Cryomethods, quick-freezing and freeze-drying, and OsO(4) vapor fixation were
      employed to preserve the original calcium distribution, and the preservation was
      verified by secondary ion mass spectrometry (SIMS). Intracellular calcium
      distribution was identified by energy-filtering transmission electron microscopy
      (EELS). Scarce calcium signals were recorded from all osteoblasts maintained in
      buffer (controls). Ionomycin addition resulted in the accumulation of calcium in
      mitochondria, and more calcium was stored in the mitochondria of osteoblasts
      involved in mineralization than in those of osteoblasts before mineralization.
      Moreover, in the former, strong calcium signals were recorded around the
      junctions between mitochondria and the endoplasmic reticulum. Thus EELS allowed
      to obtain high-resolution total calcium maps in defined intracellular structures,
      but only at elevated calcium levels.

PMID- 14673659
TI  - Carbonyl stress and detoxification ability in the male genital tract and testis
      of rats.
AB  - Carbonyl compounds, which are naturally produced and augmented under oxidative
      stress, have deleterious effects on the reproductive system. The aldo-keto
      reductase (AKR) family of enzymes catalyze the reductive detoxification of
      various carbonyl compounds in an NADPH-dependent manner. To elucidate involvement
      of AKR in detoxification of endogenously produced carbonyls in the male
      reproductive system, we investigated the differential expression and tissue
      localization of aldehyde reductase (ALR) and protein adducts produced by reaction
      with lipid peroxidation products. A strong immunoreactivity to an anti-ALR
      antibody was observed in the epithelia of the epididymis, vas deferens, seminal
      vesicle, and prostate gland. Virtually the same cells were stained with a
      monoclonal antibody (mAb) 5F6, raised against an acrolein-modified protein. In
      the testis, however, mAb5F6 specifically stained the nuclei of somatic cells and
      less differentiated spermatogenic cells. While acrolein inactivated glutathione
      reductase, an enzyme involved in recycling oxidized glutathione, AKR activity was
      affected at the high concentration only. The colocalization of lipid peroxidation
      products and AKR in the epithelia of the male genital tract indicates that these
      tissues are exposed to oxidative stress and possess a protective system
      coordinately.

PMID- 14673660
TI  - Immunodetection of osteoadherin in murine tooth extracellular matrices.
AB  - An antiserum was generated from synthetic peptides highly conserved between
      different mammalian species to immunolocalise the small leucine-rich proteoglycan
      osteoadherin (OSAD) in murine teeth. In 19-day-old embryos of rats and mice, a
      positive staining was found in incisor predentin and alveolar bone surrounding
      developing incisors and molars. In newborns, OSAD was detected at the tip of the
      first molar cusp where it accumulated in predentin concomitantly with odontoblast
      differentiation. In 2-day-old rats and mice, in the first molar, immunostaining
      revealed positive predentin, enamel matrix close to the apical pole of
      ameloblasts and a strong signal in dentin. At this stage, OSAD was detected in
      predentin in the second molar. Ultrastructural immunocytochemistry showed gold
      particles associated with collagen fibres in predentin and in foci at the dentin
      mineralisation front. Gold particles were also detected near the secretory pole
      of ameloblasts where enamel crystallites elongate. No staining was detected in
      pulp tissue and dental follicle. Restriction of OSAD expression to the
      extracellular matrix of bone, dentin and enamel suggests a role of this
      proteoglycan in the organisation of mineralised tissues.

PMID- 14673661
TI  - Vocal individual discrimination in Japanese monkeys.
AB  - The present study determines which features of the coo call are used by Japanese
      monkeys Macaca fuscata for vocal individual discrimination. First, two female
      Japanese monkeys were trained to discriminate conspecific individuals vocally,
      using an operant conditioning. Using as stimuli three unknown individuals with 30
      calls per individual, the two monkeys succeeded in discriminating new call
      exemplars from the three stimulus individuals. A discriminant analysis performed
      on calls used as stimuli indicated that start frequency of the fundamental and
      call duration were variables that can differentiate individuals efficiently.
      Then, playbacks of acoustically modified signals were used to indicate which
      vocal features are used by monkeys for the individual discrimination. Stimuli
      signals containing modified pitch or duration, or filtered so as to keep only the
      fundamental component, were tested. Results indicated that Japanese monkeys use
      multiple acoustical cues to perform vocal individual discrimination, including at
      least pitch, call duration, and harmonics. However, harmonics seem to be less
      important for discrimination than pitch and call duration.

PMID- 14673662
TI  - Surgery of the Upper Thoracic Sympathetic System. Proceedings of the 5th
      International Symposium on Sympathetic Surgery. Erlangen, Germany, 29-31 May
      2003.

PMID- 14673663
TI  - The anatomy and physiology of the sympathetic innervation to the upper limbs.
AB  - An overview of the autonomic nervous system is given. The sympathetic innervation
      of the upper limb is presented, with specific emphasis on segmental nervous
      supply and anatomical variations. In addition, the physiology and pharmacology of
      the sympathetic nervous system is introduced and discussed.

PMID- 14673664
TI  - History of sympathetic surgery.
AB  - The first reported operation on the upper sympathetic system was performed by
      Alexander in 1889. The initial indications (epilepsy, exophthalmic goiter,
      idiocy, glaucoma) are obsolete. For some subsequent indications (angina pectoris,
      vasospastic disorders, and painful conditions) sympathectomy has still a limited
      application. The main indications today are hyperhidrosis (since 1920) and
      blushing. Renewed attempts to perform the operation for psychological conditions
      have been reported. The technique of sympathectomy has been modified over the
      century, with a trend to minimize the extent of surgery: from open to endoscopic
      approaches; from resection of ganglia to thermoablation, thermotransection, and
      clipping. The sequelae of the operation (mainly compensatory hyperhidrosis)
      present a major problem in a small percentage of operated patients. Techniques of
      reversal (by nerve grafting and unclipping) have been proposed. Meticulous follow
      up studies are required to evaluate the merits of these techniques. Improved
      knowledge of the functions and interrelations of the autonomic nervous system is
      required to understand the mechanism of these sequelae and learn how to avoid or
      treat them.

PMID- 14673665
TI  - Upper thoracic sympathetic surgery. Open surgical techniques.
AB  - Four open surgical approaches have been used to perform upper thoracic
      sympathectomy. The posterior approach requires access through the posterior
      muscles of the back, and rib transection. It is a painful operation that has been
      practically abandoned in favor of the other techniques. The anterior
      transthoracic approach consists of a formal thoracotomy and never gained
      popularity. The supraclavicular approach involves dissection of several important
      anatomical structures. It requires excellent surgical dexterity, but ensures the
      easiest postoperative recovery. The last approach involves a small transaxillary
      thoracotomy. Technically, it is the easier procedure. Both the supraclavicular
      and the transaxillary approaches were widely used until the advent of
      thoracoscopic surgery. The results (rate of success, recurrences, and sequelae)
      were similar for all techniques, depending on the procedure performed on the
      sympathetic chain, not on the access route. Open approaches for upper dorsal
      sympathectomy are not used any more except in the very rare cases in which
      thoracoscopy is unfeasible.

PMID- 14673666
TI  - Indications for endoscopic thoracic sympathectomy.
AB  - The thoracoscopic approach to the sympathetic chain has diminished the trauma of
      previous open sympathectomy. The minimal trauma has opened the way to manipulate
      the chain for several conditions. Hand sweat is the most common indication
      resulting in patient satisfaction 2-13 years after surgery in more than 90%. High
      satisfaction was also obtained in patients with angina pectoris and a very
      disabling condition, facial blushing (85 %). Somewhat poorer results were
      obtained in patients with facial and axillary sweating. In patients with Mb
      Raynaud-all had recurrences within a year. Since severe side effects, especially
      compensatory sweating, may occur, the ETS procedure should be reserved only for
      patients with severe problems where other treatments have failed.

PMID- 14673667
TI  - Psychoneurological applications of endoscopic sympathetic blocks (ESB).
AB  - In addition to more widely and longer known indications of ETS, various
      neurological disorders and psychologically stressful situations in their worst
      expressions might be alleviated by the reversible ESB procedure. The patients
      with social phobia, especially those who have also blushing and/or stage fright
      type of heart racing, benefit from the ESB. The disturbances of the sympathetic
      nervous system, e. g. in Parkinson's disease and multiple system atrophy might be
      alleviated with sympathetic block, especially the extrapyramidal symptoms in
      these diseases. In migraine, sympathetic surgery has been noted to give some
      help. The unilateral left-sided block has been effective in long QT-syndrome type
      arrhythmias. In schizophrenia, the phobic, paranoic or confusional reactions have
      been tentatively treated by the sympathetic block.

PMID- 14673668
TI  - The technique of endoscopic thoracic sympathectomy: resection, clipping and
      cautery.
AB  - Three authors describe their individual technique for performing ETS. These are
      1) a two-port approach under singlelung ventilation using a double-lumen tube and
      cutting the chain, 2) a two-port approach under endotracheal or mask anesthesia
      and clipping of the chain, and 3) a single-port approach under endotracheal or
      mask anesthesia and cautery of the chain. The sections are purely didactic and no
      attempt is made to compare or contrast the methods.

PMID- 14673669
TI  - Results of endoscopic thoracic sympathectomy (ETS) on hyperhidrosis, facial
      blushing, angina pectoris, vascular disorders and pain syndromes of the hand and
      arm.
AB  - Endoscopic thoracic sympathectomy (ETS) has gained increasing popularity due to
      its minimally invasive character. Despite the simplicity of the procedure, non
      surgical options should always be considered as the first line of treatment. The
      complication risk of ETS is low but side effects, primarily compensatory sweating
      (CS) of mainly the trunk, may be severe enough to cause regret of the procedure.
      The risk/benefit ratio should always be discussed with the patient. Severe palmar
      hyperhidrosis and facial blushing respond very well to ETS with a high patient
      satisfaction rate. Facial hyperhidrosis is effectively treated with ETS, but is
      associated with a high risk for severe CS. Axillary hyperhidrosis is best treated
      by means other than ETS. The use of ETS for pain syndromes, vascular
      insufficiency and angina pectoris is not well supported by scientific evidence,
      making careful patient selection mandatory.

PMID- 14673670
TI  - Specific complications and mortality of endoscopic thoracic sympathectomy.
AB  - Endoscopic Thoracic Sympathectomy (ETS) has gained an increasing popularity due
      to its minimal invasive character. Despite the simplicity of the procedure, non
      surgical options should always be considered as the first line of treatment. The
      complication risk of ETS is low but side effects, primarily compensatory sweating
      (CS) of mainly the trunk may be severe enough to cause regret of the procedure.
      The risk/benefit ratio should always be discussed with the patient. Severe palmar
      hyperhidrosis and facial blushing respond very well to ETS with a high patient
      satisfaction rate. Facial hyperhidrosis is effectively treated with ETS but is
      associated with a high risk for severe CS. Axillary hyperhidrosis is best treated
      by other means than ETS. The use of ETS for pain syndromes, vascular
      insufficiency and angina pectoris is not well supported by scientific evidence,
      making mandatory careful patient selection.

PMID- 14673671
TI  - Sequelae of endoscopic sympathetic block.
AB  - Endoscopic sympathetic block as a treatment for primary hyperhidrosis is
      associated with certain sequelae. The reported occurrence of side effects still
      varies in the literature. As the majority of patients describe sequelae after
      sympathetic surgery, the frequency and importance of these persisting changes are
      still underestimated. Patient's informed consent should include and define side
      effects like gustatory sweating, olfactory sweating and bradycardia as likely,
      and compensatory sweating as obligatory.

PMID- 14673672
TI  - The pathophysiology of cervical and upper thoracic sympathetic surgery.
AB  - The main effect of upper thoracic sympathectomy is sudomotor. To abolish sweating
      of the palms, T(2) ganglionectomy (often with the addition of T(3)) was
      invariably performed. To prevent axillary sweating, additional T(4) ablation was
      recommended. Sympathectomy produces a vasodilatatory cutaneous effect. The
      circulation in the muscles, however, is unaltered or may even be reduced. It also
      appears that improved skin blood flow is on the thermoregulatory, not nutritive
      level. It seems that chronic surgical sympathectomy does not cause major changes
      in the vascular function of the forearm. Although the exact pathophysiological
      mechanism of blushing is still obscure, bilateral upper dorsal sympathectomy
      alleviates this phenomenon. T(2)-T(3) ganglionectomy significantly decreases
      pulse rate and systolic blood pressure, reduces myocardial oxygen demand,
      increases left ventricular ejection fraction and prolongs Q-T interval. A certain
      loss of lung volume and decrease of pulmonary diffusion capacity for CO result
      from sympathectomy. Histomorphological muscle changes and neuro-histochemical and
      biochemical effects have also been observed.

PMID- 14673673
TI  - Comparative analysis of T3 selective division of rami communicantes (ramicotomy)
      to T3 sympathetic clipping in treatment of palmar hyperhidrosis.
AB  - Compensatory sweating is a major complaint following endoscopic thoracic
      sympathetic surgery in treatment of palmar hyperhidrosis. T3 ramicotomy was
      applied in order to decrease compensatory sweating. From Oct 1999 to June 2002,
      forty patients underwent T3 sympathetic clipping (group I), and 68 patients
      underwent T3 ramicotomy (group II) to treat palmar hyperhidrosis. We
      retrospectively analyzed the rate of satisfaction, result of operation, and grade
      of compensatory sweating. In group I, 36 patients (90%) showed decreased sweating
      on both hands, 4 patients (10 %) persistent sweating on both hands. In group II,
      46 patients (67.6%) had decreased sweating on both hands, 14 patients (23.5 %)
      had persistent sweating on both hands, and 8 patients (8.9 %) had persistent
      sweating in one hand. The rate of satisfaction was 82.5 % (33/40) in group I and
      67.6 % (46/68) in group II with no significant statistic difference (p = 0.067).
      Excluding patients with persistent sweating postoperatively, the rate of
      compensatory sweating in group II was 67.4%, which was significantly lower than
      in group I 94.1%, with a p value of 0.003. Although the rate of persisting
      sweating after operation was high, T3 ramicotomy resulted in lower rate of
      compensatory sweating compared to T3 sympathetic clipping.

PMID- 14673674
TI  - Treatment of palmar hyperhidrosis by endoscopic clipping of the upper part of the
      T4 sympathetic ganglion. Preliminary results.
AB  - Endoscopic thoracic sympathetic surgery is a safe and effective method of
      treating palmar hyperhidrosis. Although hand dryness is the positive outcome of
      surgery, a residual amount of moisture in the hand is believed to improve the
      quality of life. Reflex sweating is a well-recognized and annoying complication
      that surgeons endeavor to avoid. From May 1, 2002 to July 31, 2002, 52 patients
      suffering from palmar hyperhidrosis were operated on by means of endoscopic
      clipping of the upper part of the T4-sympathetic ganglion (Upper ESB4). There
      were 24 males and 28 females with a mean age of 25 years. The mean follow-up
      period was 8.3 months. The patients answered a detailed questionnaire addressing
      the following issues: the recurrence rate, the degree of hand dryness, the extent
      of and areas of reflex sweating, the occurrence of gustatory and facial sweating,
      and the degree of satisfaction. The surgical outcome was satisfactory. Most
      patients demonstrated no or only slight hand sweating. Moderate sweating without
      discomfort was experienced in 9% of patients. Only 25% of patients required the
      use of lotion for hand dryness. Reflex sweating was observed in 87.5% of the
      patients but extremely uncomfortable in only 3.2%. Ninety-four percent of
      patients were satisfied. The remaining 6% were not satisfied but did not regret
      the operation. Although the duration of the follow-up period in this study was
      relatively short, we could obtain results comparable to other data in the
      literature. This is a simpler procedure and less damaging to the sympathetic
      system.

PMID- 14673675
TI  - Experience with limited endoscopic thoracic sympathetic block for hyperhidrosis
      and facial blushing.
AB  - Endoscopic thoracic sympathetic block (ESB) has recently become a popular
      modification of sympathetic surgery, as it offers the potential chance of
      reversibility. In order to reduce side effects such as compensatory sweating
      limited ESB at the levels of the T2, T3 or T4 ganglia has been recommended
      (Lin/Telaranta classification). We present our experience and initial results
      with this technique. From 6/2001 to 2/2003, 184 ESB procedures were performed in
      94 patients. ESB4 was carried out in 53 patients for hyperhidrosis (HH) of the
      upper limb. In 23 patients ESB3 was performed for craniofacial HH and 18 patients
      suffering from facial blushing were treated by ESB2. Median follow-up was 5.2-7.5
      months.Success rates were similar (~100%) in all groups. Compensatory sweating
      was found in 25% in the ESB3 compared to 12.5 % in the ESB2 and 8.5 % in the ESB4
      group (p < 0.05). Gustatory sweating did not differ significantly between the
      groups (6.3 % in ESB2, 5% in ESB3 and 2.1 % in ESB4 group). Five patients were
      reoperated in the ESB3 group (3 because of a side-difference of the effect in the
      face, 1 patient due to incomplete Horner's syndrome and 1 due to massive
      compensatory sweating). In the ESB4 group all patients were satisfied with the
      outcome, whereas in the ESB2 group 6.3% and in the ESB3 group 13.9% were partly
      satisfied. Limited sympathetic surgery offers comparably high success and
      satisfaction rates along with a low rate of side effects.

PMID- 14673676
TI  - Endoscopic thoracic sympathicotomy for the treatment of complex regional pain
      syndrome.
AB  - Complex regional pain syndrome (CRPS) is a neurological syndrome that usually
      affects one or more extremities, and can cause chronic pain and permanent
      deformities. This study aimed to analyze the efficacy of endoscopic thoracic
      sympathicotomy (ETS) in the treatment of pain in patients with CRPS stage II and
      III operated on in our clinic. Seven patients (four males and three females; mean
      age 34.7 years; American Society of Anesthesiologists physical status 1 and 3;
      post-operative follow-up from 5 to 49, mean 33.6 months), with diagnoses of CRPS
      type I and II, stages II and III, were operated on as outpatients. The
      sympathetic chain was severed over the ribs from T2 to T5, along with the
      communicating rami of these segments, including the Kuntz nerve. The ETS was
      performed bilaterally in four patients. Pain was assessed using a visual analogic
      scale (VAS) from 0 to 10. Pain disappeared in all patients operated on during
      rest (VAS = 0). Four patients reported pain during repeated movement of the
      affected limb, the intensity being lower than before surgery (mean VAS = 2.62 vs
      8.46). Analgesics were no longer needed after surgery. All patients had their
      quality of life improved. According to the present investigation, ETS, as
      described, was efficient for the relief of pain and improvement of the quality of
      life in patients with CRPS stage II and III.

PMID- 14673677
TI  - Fast track endoscopic thoracic sympathicotomy.
AB  - The length of hospital stay is an important factor of cost and psychological
      discomfort in the treatment of hyperhidrosis by endoscopic thoracic
      sympathicotomy (ETS). Our experience enrolls 1587 patients operated on an
      outpatient basis in the last 10 years and seven months. This study aimed to
      confirm that ETS can be performed on an outpatient basis. Fifty-two consecutive
      patients (30 males and 22 females) were submitted to ETS under general anesthesia
      using a single lumen endotracheal tube, with lung collapse by intrapleural
      injection of CO(2). The sympathetic chain and the communicating rami were severed
      at different levels according to hyperhidrosis location. Patients were physical
      state American Society of Anesthesiologists 1 and 2. Age varied between 13 and 55
      years (27.3 +/- 10.2 years). They were monitored with ECG, SPO2, NIBP, expired
      CO(2), sevoflurane analyzer, and airway pressure. Normal saline (40.0 +/- 2.7
      ml/kg) was infused intravenously. The drugs used were propofol, alfentanil,
      rocuronium, ondansetron, dexamethasone, dipyrone, cetoprofene and sevoflurane.
      Anesthesia and post-operative data were analyzed. Post-operative thoracic X-rays
      were taken in 20 patients before discharge. Anesthesia lasted 67.2 +/- 20.8
      minutes, and the surgical procedure took 46.3 +/- 20.9 minutes. The patients
      stayed 18.0 +/- 11.0 minutes in the post-anaesthetic care unit and were
      discharged from hospital after 150.3 +/- 43.1 minutes. The only abnormal post
      operative event observed was insignificant residual carbothorax, found in 2 (10%)
      of the thoracic X-rays taken. In conclusion, this study confirmed that ETS can be
      performed safely on an outpatient basis.

PMID- 14673678
TI  - Microinvasive resectional sympathectomy using the harmonic scalpel. A more
      effective procedure with fewer side effects for treating essential hyperhidrosis
      of the hands, face or axillae.
AB  - Compensatory sweating remains one of the most unpredictable and debilitating
      complications of sympathectomy for hyperhidrosis. There appears to be a
      significant difference in compensatory sweating rates seen between the different
      techniques utilized to treat hyperhidrosis. Resectional techniques have
      historically resulted in excellent symptom relief with relatively low levels of
      severe post-op compensatory sweating. The advent of video-assisted approaches to
      the treatment of hyperhidrosis has led to other procedures including
      ablation/cautery, cutting and clipping of the nerve all of which report
      compensatory sweating rates between 70 and 100%. We have developed a minimally
      invasive video-assisted approach to sympathetic nerve resection. We studied 486
      patients with severe essential hyperhidrosis affecting the hands, feet, axillae
      and face in variable combinations, who underwent bilateral resection of T2 and T3
      for hand, facial or head sweating. 100% relief of sweating was noted in all
      cases. For axillary sweating the addition of T4 resection has resulted in
      complete relief of axillary hyperhidrosis symptoms. In this patient population
      our overall compensatory sweating rate has been approximately 18% with
      significant compensatory sweating occurring in less than 2% of patients.

PMID- 14673679
TI  - Is the internet the best resource for blushers?
AB  - Blushing can be a disabling condition that causes sufferers great distress. It
      causes patients to become socially isolated, frequently being labelled as "shy".
      Any referral to their condition is embarrassing; even a discussion with a health
      care professional requires a great deal of courage. Even then, the information
      from non-specialists is often inaccurate and inadequate and fails to inform
      patients of the possible treatment options available. In today's era the internet
      has become an important information medium. This information on almost any
      subject is widely available to the general public and can be accessed at any
      time. It is available to blushers and health care professionals alike. It offers
      a non-embarrassing method of seeking help for an embarrassing condition. It is a
      medium for specialists to inform sufferers incognito about such a condition. We
      report our experience from our website: a generalised hyperhidrosis, blushing and
      sympathectomy information web site (www.sympathectomy.co.uk) by analysing the
      number of hits and requests for information. We discuss the statistics of
      internet access to our website including the "hit rate" and enquiry rate.
      Paradoxically 75% of all enquiries have been from blushers with only 25% coming
      from patients with hyperhidrosis.A properly designed, accurate and dynamic web
      site tailored towards users' needs can be used to effectively educate an
      information hungry but shy group.

PMID- 14673680
TI  - Effects of gender and level of surgical sympathetic block on vasoconstrictor
      function.
AB  - Interruption of sympathetic outflow by surgical sympathetic block has been used
      to treat hyperhidrosis for decades. In this study the effect of gender and the
      level of sympathetic block (T2 vs. T3) on the rewarming kinetics following ice
      water immersion were assessed in a prospective study on 60 hyperhidrosis patients
      before, 2 days, and 3 months postoperatively. Rewarming kinetics following
      endoscopic sympathetic block (ESB) was massively enhanced 2 days post
      operatively, but had returned to pre-operative conditions at the 3 month follow
      up for ESB at level T3. ESB at level T2 provoked significantly faster rewarming
      as compared to T3 at the 2 day and 3 month follow-up. Independent of the level of
      ESB, there was a slower rewarming in women already pre-operatively. This gender
      difference was clearly reduced at the 2 day follow-up, but had increased again at
      the 3 month follow-up. There was no correlation between the rewarming kinetics of
      the fingertips and palmar sweating. We conclude that for the sympathetic
      vasoconstriction of the fingertips the sympathetic ganglion T2 is crucial. Gender
      differences have to be taken into account when assessing effect of ESB by cold
      induced vasoconstriction. It remains to be established whether the quantification
      of vasoconstriction has some predictive value for the long-term prognosis of
      sudomotor blockade.

PMID- 14673681
TI  - Differential effects of surgical sympathetic block at the T2 and T4 level on
      vasoconstrictor function.
AB  - Endoscopic sympathetic block (ESB) is used as a treatment of excessive palmar
      sweating. In a prospective study we compared the effect of ESB at the level of
      the second (T2) and fourth thoracic ganglion (T4) on vasoconstriction and
      sweating of the hands. Sympathetic vasoconstriction was measured by
      computerassisted infrared thermography following ice water immersion of the hands
      in 22 hyperhidrosis patients before, two days and 3 months post op. In addition,
      palmar sweating before and 3 months post op was assessed by sudometry. After ESB
      the rewarming was accelerated in both T2 and T4 patients, but was significantly
      slower in the T4 group. Three months postoperatively rewarming had returned to
      the preoperative pattern in T4 patients but was still significantly faster in the
      T2 group. These effects were more pronounced in the fingertips than the hand
      dorsum. Sudomotor function was blocked in all T2 patients but had relapsed in 2
      patients in the T4 group. Two T4 patients had not shown an effect on sudomotor
      function postoperatively. The normalization of rewarming kinetics may be
      explained by remaining fibers, denervation hypersensitivity or stimulation of
      catecholamine receptors, or neuronal reorganization. The effect of ESB T4 on
      sudomotor function has to be proven.

PMID- 14673682
TI  - In vivo extracellular recording of sympathetic ganglion activity in a chronic
      animal model.
AB  - Surgery of the sympathetic system is performed for a variety of indications,
      hyperhidrosis being a major one. Despite excellent results, sympathectomy for
      hyperhidrosis bears a number of sequels, some of which may be devastating.
      Several surgical methods, empirically advocated to alleviate these problems, have
      only limited success. Chronic in vivo recording of the electrical activity from
      sympathetic ganglia may assist in understanding and clarifying complex problems
      of sympathetic surgery; however, no suitable method has been reported. An
      electrode device developed by our group was implanted on the stellate ganglion,
      in a chronic animal model (dog). The signals obtained were amplified, filtered,
      and transmitted via an A/D interface to be acquired and saved on a computer,
      using special software which we developed. Our method enabled the separate
      recording of neuroelectrical signals, ECG, and respiration waves. An additional
      software program, also developed by our group, was used to analyze the data. This
      chronic animal model allows investigation of surgical and pharmacological
      manipulations of the sympathetic system.

PMID- 14673683
TI  - Relation between hemodynamic changes after endoscopic transthoracic
      sympathicotomy and the number of sympathetic segments operated.
AB  - We examined the relation between hemodynamic changes after endoscopic
      transthoracic sympathicotomy (ETS) and the number of sympathetic segment
      operated. Cardiac functional indices using echocardiography and plasma
      noradrenaline concentration (NOR) were measured before and after ETS in 25
      patients with palmar hyperhidrosis. Patients were divided into 2 groups. Group
      Th2-3 consisted of 16 patients (mean age 28 +/- 8 years),who underwent Th2-3 ETS.
      Group Th2-4 consisted of 6 patients (mean age 29 +/- 9 years), who underwent Th2
      4 ETS. Before ETS, all hemodynamic parameters and NOR were similar between the 2
      groups. After ETS, heart rate, systolic, diastolic, and mean blood pressures,
      rate-pressure product, and NOR decreased,whereas left ventricular end-systolic
      volume index, cardiac index, and ejection fraction did not change in the 2
      groups. Systemic vascular resistance decreased in group Th2-4, whereas it did not
      change in group Th2-3. Left ventricular end-diastolic volume index and stroke
      index increased in group Th2-3, whereas it did not change in group Th2-4. After
      ETS, rate-pressure product, systolic, diastolic, and mean blood pressures in
      group Th2-4 were smaller than those in group Th2-3, whereas other parameters were
      similar between the 2 groups. Among percent changes in all hemodynamic parameters
      and NOR occurring after ETS, only the percent decrease in systolic blood pressure
      in group Th2-4 was larger than that in group Th2-3 (-15 +/- 12 % vs.-4+/-8%,
      respectively, p < 0.05). These findings suggest that only the change in blood
      pressure is related to the difference in the number of sympathetic segment
      operated.

PMID- 14673684
TI  - Variations in dynamic lung compliance during endoscopic thoracic sympathectomy
      with CO2 insufflation.
AB  - Endoscopic thoracic sympathectomy (ETS) is the preferred surgery for treatment of
      intractable palmar hyperhidrosis (PH). General anesthesia with onelung collapsed
      ventilation (OLCV) using single-lumen tracheal tube (SLT), is our preferred
      anesthetic technique for ETS. Intrapleural CO(2) insufflation (capnothorax) was
      used to ensure lung collapse. The current study examined the effects of
      capnothorax on dynamic lung compliance (DLC) of the ventilated lung during ETS.
      After obtaining written informed consent, 10 adult male patients ASA I&II
      undergoing ETS were studied. Their average age and weight were 25 +/- 7 yr and 67
      +/- 8 kg. General anesthesia with SLT and OLCV technique was used. Capnothorax
      with intrapleural pressure (IPP) of 10 mmHg was initially used, then it was
      reduced and maintained at 5 mmHg throughout the operation. Anesthesia delivery
      unit (Datex Ohmeda type A_Elec, Promma, Sweden) was used where airway pressures
      and DLC were displayed during OLCV. A computer program (SPSS 9.0 for Windows;
      SPSS Inc., Chicago, IL) was used for statistical analysis of the data obtained.
      One way analysis of variance (ANOVA) was used for analysis of data before, during
      and after OLCV. P<0.05 was considered significant. The mean values of the DLC
      were 52 +/- 6, 30 +/- 3, 39 +/- 5 and 53 +/- 9 ml/cmH(2)O before, during (at 10
      and 5 mmHg IPP) and after OLCV respectively with significant differences before
      and at 10 and 5mmHg IPP. In conclusions, during OLCV and capnothorax for ETS, DLC
      tends to decrease with increasing of intrapleural CO(2) insufflation pressure.
      However, in short procedures it has no deleterious postoperative effect. To the
      best of our knowledge this is the first study performed to investigate DLC
      changes during OLCV with capnothorax.

PMID- 14673687
TI  - Blood pressure, attention and cognition: drivers and air traffic controllers.

PMID- 14673688
TI  - The meaning of sitting hypotension: still unclear.

PMID- 14673689
TI  - Nitrate stimulated tilt testing: clinical considerations.

PMID- 14673690
TI  - Nitrosative stress in early Type 1 diabetes. David H. P. Streeten Memorial
      Lecture.
AB  - Although hyperglycemia has been shown to cause peripheral nerve dysfunction in
      patients with diabetes, the biochemical mechanisms for this effect are poorly
      understood. The excessive production of reactive oxygen species and reactive
      nitrogen species has been proven to be detrimental in experimental diabetes, but
      there is little evidence that these metabolic events take place clinically and
      are physiologically important in man. To assess this we measured nitrite and
      nitrate (indices of nitric oxide production), nitrotyrosine (an index of
      peroxynitrite), 8-isoprostaglandin F-2 alpha, an isoprostane reflective of
      oxidative stress and lipid peroxidation, and uric acid, an index of antioxidant
      defense in patients with recently diagnosed Type 1 diabetes and aged-matched
      controls. The diabetic patients were followed for three years. We documented the
      overproduction of nitric oxide and increased lipid peroxidation in early diabetes
      and showed these changes had detectable adverse effects on peripheral nerve
      function especially sympathetic sudomotor nerves. We documented the suppression
      of uric acid and showed this was associated with multiple abnormalities in
      autonomic function. In addition, we present indirect evidence that overproduction
      of reactive oxygen species and reactive nitrogen species have adverse effects on
      beta cell function and blood pressure.

PMID- 14673691
TI  - Heart rate and blood pressure during initial LBNP do not discriminate higher and
      lower orthostatic tolerant men.
AB  - High (n = 7, 25 +/- 2 yr) and low (n = 8, 26 +/- 3 yr) lower body negative
      pressure (LBNP) tolerant men were exposed to -15 mmHg (for 12 min) followed by 
      50 mmHg (for 21 min) to test the hypothesis that heart rate (HR) and blood
      pressure (BP) data from acute exposure to LBNP would not discriminate between the
      higher and lower tolerance men. Central venous pressure (CVP), HR, and systolic
      (SBP) and diastolic (DBP) blood pressures measured before and at 15-s intervals
      during LBNP and calculated mean arterial pressure (MAP), pulse pressure (PP), and
      work of the heart (HW) were analyzed using ANOVA (p < or = 0.05). There were no
      significant changes in HR, SBP, DBP, MAP, PP, or HW during exposure to -15 mmHg
      LBNP. Throughout -50 mmHg LBNP, there were no significant changes in SBP, MAP,
      PP, or HW, but HR increased significantly (high tolerance by 30%, low tolerance
      by 40%) with no difference between groups. Diastolic blood pressure changed by
      +7.6 % (NS) in the high group and by -3.3% (NS) in the low group; the initial
      exposure to -50 mmHg resulted in a significant difference between groups for the
      first 45 s. Central venous pressure decreased significantly at -15 mmHg (high
      group by -33%, low group by -38 %) and at -50 mmHg (high group by -70%, low group
      by -73%) with no difference between groups. Thus, HR and BP responses at -15 and 
      50 mmHg of LBNP for 30 min do not discriminate between the high and low tolerant
      men and questions the validity and usefulness of the clinical stand test to
      predict orthostatic tolerance.

PMID- 14673692
TI  - Reduced cognitive performance and prolonged reaction time accompany moderate
      hypotension.
AB  - The aim of the present study was to investigate the impact of hypotension on
      attentional and motor performance. Twenty-six moderately hypotensive subjects
      (mean systolic blood pressure = 108.8 mmHg) were compared to 29 normotensive
      controls (mean systolic blood pressure = 123.5 mmHg). The participants were
      presented with two standard German tests of attention ("Aufmerksamkeits
      Belastungs-Test", Test d2; "Zahlen-Verbindungs-Test", ZVT). Additionally,
      reaction times to acoustic signals were measured. The hypotensive group showed
      significantly prolonged reaction times (p = 0.007) as well as reduced performance
      speed (p = 0.004) and lower concentration capacity (p = 0.014) in the test d2. In
      the ZVT as well a slightly poorer performance in hypotensives was observed (p =
      0.088). Moreover, significant partial correlations between systolic blood
      pressure and the performance measures with age as covariate were found
      (performance speed: r = 0.28; concentration capacity: r = 0.22; reaction time: r
      = 0.33). A lowered cerebral perfusion in hypotensives and an altered activity of
      baroreceptors located in the carotid sinus are discussed as possible underlying
      psychophysiological processes mediating the relationship between blood pressure
      and cognitive performance. This study is the first to provide empirical evidence
      for the relation between attentional deficits and even moderately lowered blood
      pressure.

PMID- 14673693
TI  - Cardiac autonomic responses to progressive head-up tilt in individuals with
      paraplegia.
AB  - Beat-to-beat fluctuations in heart rate are partially controlled by the autonomic
      nervous system and may be altered by a spinal cord injury. The purpose of the
      present investigation was to examine the role of the autonomic nervous system in
      modulating the heart rate response to head-up tilt (HUT) in subjects with low
      lesion paraplegia. Nineteen subjects with paraplegia and nine age-, height-, and
      weight-matched control subjects consented to participate. A three lead ECG was
      used to acquire heart rate (HR), cardiac sympathetic [low frequency component of
      R-R interval variability (LFRRI)], vagal [high frequency component of R-R
      interval variability (HFRRI)] and sympatho-vagal balance (LF/HF). A finger
      photoplethysmograph was used to assess beat-to-beat blood pressure for the
      estimation of sympathetic vasomotor tone [low frequency component of peak
      systolic blood pressure variability (LFSBP)]. The results showed a significant
      main effect for tilt angle for the HR response to HUT, which was comparable
      between the groups. LFRRI was significantly increased (P < 0.001) and HFRRI was
      significantly reduced (P < 0.001) across tilt angle in the control group, whereas
      subjects with paraplegia demonstrated no significant change in LFRRI, but
      significantly reduced HFRRI (P < 0.001) across tilt angle. There was a
      significant interaction effect for LF/HF (P < 0.05). LFSBP was significantly
      reduced in the group with paraplegia compared to controls (P < 0.05). These
      findings suggest that although cardiac autonomic control is intact, there is a
      blunted sympathetic response to HUT in subjects with low lesion paraplegia, which
      may implicate an altered baroreceptor response to acute orthostatic provocation.

PMID- 14673694
TI  - Plasma volume and hematocrit changes in recurrent fainters.
AB  - The pooling of blood in the limbs is the beginning of a chain of events which
      brings about the reflex syncope. Observations have confirmed that the reduction
      of plasma volume is also a factor pathogenetically determinant in the provocation
      of a faint. During orthostatic stress, plasma volume shifts towards the
      interstitial spaces of the infra-diaphragmatic vascular network, thus,
      contributing greatly to the reduction in the circulating volume. The aim of the
      present study was to calculate whether during orthostasis there was indeed a
      reduction in plasma volume and to what extent in a population at high risk for
      fainting. A comparative study of 50 recurrent fainters and 37 controls was
      performed. Each group was studied both in a supine (before) and orthostatic
      (after) position. Blood samples were taken to determine the hematocrit and
      hemoglobin values. The percentage variation of these values was calculated in
      order to obtain the reduction in plasma volume, i. e., the expression of the
      amount of plasma accumulated in the interstitial spaces. A significant difference
      in hematocrit and hemoglobin variation (before vs. after) was found between
      patients and controls. Plasma volume variation before vs. after (17.1 % in
      patients vs. 8.6 % in controls) was then calculated using these measurements. The
      difference in plasma volume variation between patients and controls can be
      interpreted as a co-factor together with the pooling of plasma in the
      pathogenesis of reflex fainting. This study illustrates an easy way to evaluate
      the role of plasma volume reduction in the pathogenesis of vasovagal syncope.

PMID- 14673695
TI  - Poor baroreflex gain is a marker of heightened sympathetic activity post
      tachycardia termination in humans.
AB  - We hypothesized that sympathetic nerve activity (SNA) remains elevated after
      tachycardia termination in patients with low baroreflex gain (BRG), and decreased
      to or below baseline in patients with high BRG. In a cohort of patients who
      participated in a previously published study [3], BRG, SNA, blood pressure, and
      central venous pressure were measured immediately after the termination of
      simulated tachycardia. While the hemodynamic responses following tachycardia
      termination were similar in both groups, SNA remained elevated in patients with
      low BRG compared to a decrease below baseline levels in patients with high BRG (p
      = 0.04). Increased sympathetic activity following tachycardia termination could
      be arrhythmogenic and might play a role in the genesis of recurrent ventricular
      arrhythmias following tachycardia termination.

PMID- 14673696
TI  - Seated postural hypotension is common among older inpatients.
AB  - Bed-rest > 12 hours produced postural hypotension (PH) in 54% of seated older
      inpatients. PH was multifactorial, equally initiated throughout 5 minutes and
      symptoms arised frequently following small blood pressure drops. In this context
      PH should be anticipated and prevented.

PMID- 14673697
TI  - Transdermal absorption of estradiol in normal subjects and in patients with
      peripheral neuropathies.
AB  - The relationship of disturbed autonomic skin innervation to altered transdermal
      absorption in polyneuropathy is not yet clear. In this study we measured serum
      estradiol in 29 normals and 10 polyneuropathy patients to assess potential
      differences of estradiol uptake from different skin sites.

PMID- 14673698
TI  - Vasodepressor syncope and the diagnostic accuracy of the head-up tilt test with
      sublingual glyceryl trinitrate.
AB  - Thirteen syncopal subjects and thirteen asymptomatic controls were examined by
      head-up tilt (HUT) with and without sublingual GTN. Adding GTN to HUT improved
      the sensitivity of the test (8 % to 46%) but decreased specificity (100 % to 54
      %).

PMID- 14673704
TI  - Mutation in slowmo causes defects in Drosophila larval locomotor behaviour.
AB  - We have identified a mutant slowmotion phenotype in first instar larval
      peristaltic behaviour of Drosophila. By the end of embryogenesis and during early
      first instar phases, slowmo mutant animals show a marked decrease in locomotory
      behaviour, resulting from both a reduction in number and rate of peristaltic
      contractions. Inhibition of neurotransmitter release, using targeted expression
      of tetanus toxin light chain (TeTxLC), in the slowmo neurons marked by an
      enhancer-trap results in a similar phenotype of largely absent or uncoordinated
      contractions. Cloning of the slowmo gene identifies a product related to a family
      of proteins of unknown function. We show that Slowmo is associated with
      mitochondria, indicative of it being a mitochondrial protein, and that during
      embryogenesis and early larval development is restricted to the nervous system in
      a subset of cells. The enhancer-trap marks a cellular component of the CNS that
      is seemingly required to regulate peristaltic movement.

PMID- 14673705
TI  - Soluble epoxide hydrolase variant (Glu287Arg) modifies plasma total cholesterol
      and triglyceride phenotype in familial hypercholesterolemia: intrafamilial
      association study in an eight-generation hyperlipidemic kindred.
AB  - Plasma lipid and lipoprotein in general reflect the complex influences of
      multiple genetic loci, for instance, even familial hypercholesterolemia (FH), a
      representative example of monogenic hyperlipidemia, often presents with
      phenotypic heterogeneity. In the course of investigating familial coronary artery
      disease in Utah, we studied 160 members of an eight-generation extended family of
      FH in which 69 members were affected with type IIa hyperlipoproteinemia (HLPIIa;
      high plasma cholesterol) and ten with type IIb hyperlipoproteinemia (HLPIIb; high
      plasma cholesterol as well as plasma triglyceride). Soluble epoxide hydrolase (
      EPHX2, sEH) plays a role in disposition of epoxides in plasma lipoprotein
      particles. Intrafamilial correlation analysis of the modifier effect of Glu287Arg
      substitution in the EPHX2 gene was carried out among 79 LDLR mutation carriers
      and 81 noncarriers. In the carriers, plasma cholesterol levels were elevated
      among carriers of the 287Arg allele (mean +/- SD=358 +/- 72 mg/dl) in comparison
      with 287Glu homozygotes (mean +/- SD=302 +/- 72 mg/dl) (p=0.0087). Similarly, in
      the LDLR mutation carriers, the plasma triglyceride levels were elevated among
      carriers of the 287Arg allele (mean +/- SD=260 +/- 100 mg/dl) in comparison with
      287Glu homozygotes (mean +/- SD=169 +/- 83 mg/dl) (p=0.020). No such gene
      interactive effect was observed among noncarriers of the LDLR mutation. Half of
      the patients who presented with HLPIIb had inherited a defective LDLR allele as
      well as an EPHX2-287Arg allele, whereas the majority who presented with HLPIIa
      had a defective LDLR allele but not an EPHX2-287Arg allele. These results
      indicate a significant modification of the phenotype of FH with defective LDLR
      allele by EPHX2-287Arg variation in our studied kindred.

PMID- 14673706
TI  - Deregulated expression of KRAP, a novel gene encoding actin-interacting protein,
      in human colon cancer cells.
AB  - We have identified a novel gene, designated KRAP (Ki- ras-induced actin
      interacting protein), encoding a protein of 1,259 amino acids with coiled-coil
      regions and transmembrane regions, from the cDNA library of human colon cancer
      HCT116 cells, as one of the genes upregulated by activated Ki- ras. While KRAP
      was rarely expressed in normal colon epithelium, deregulated constitutive KRAP
      expression was observed in some other colon cancer cells. In normal tissues, KRAP
      was strongly expressed in pancreas and testis. Anti-KRAP polyclonal antibodies
      detected endogenous KRAP as the molecular size of Mr 180,000, and
      immunofluorescence microscopy and cytochalasin E treatment revealed that KRAP was
      clearly associated with the actin filaments. Furthermore, KRAP was localized as a
      membrane-bound form with extracellular regions. These results together suggested
      KRAP might be involved in the regulation of filamentous actin and signals from
      the outside of the cells.

PMID- 14673707
TI  - Identification of a novel splice site mutation of CLCN5 gene and characterization
      of a new alternative 5' UTR end of ClC-5 mRNA in human renal tissue and
      leukocytes.
AB  - Mutations in the CLCN5 gene have been detected in Dent's disease and its
      phenotypic variants (X-linked recessive nephrolithiasis, X-linked recessive
      hypophosphatemic rickets, and idiopathic low-molecular-weight proteinuria of
      Japanese children). Dent's disease is a tubular disorder characterized by low
      molecular-weight proteinuria, and nephrolithiasis associated with
      nephrocalcinosis and hypercalciuria. ClC-5 is the first chloride channel for
      which a definitive role in the trafficking and acidification-dependent recycling
      of apical membrane proteins has been established. In the course of CLCN5 SSCP
      analysis in patients with hypercalciuric nephrolithiasis, we detected a novel
      mutation at intron 2 of the CLCN5 gene, a T-to-G substitution, located 17 bp
      upstream of the AG acceptor site. To determine the effect of IVS2-17 T>G mutation
      on the correct splicing of intron 2, we studied ClC-5 transcripts in a patient's
      peripheral blood leukocytes by means of quantitative comparative RT/PCR, and
      found a new ClC-5 5' UTR isoform characterized by the untranslated exon 1b and by
      retention of intron 1b. This new isoform--isoform B1--was not correlated with
      mutation since it was detected also in control leukocytes and in renal tissues of
      kidney donors, thus confirming its physiological role. By RACE analysis we
      determined the putative transcriptional start site which is located at intron 1a,
      251 nt upstream of the first nucleotide of the untranslated exon 1b. ORF analysis
      revealed that intron 1b retention in isoform B1 stabilizes the initiation of
      translation to the AGT at position 297 of the ClC-5 cDNA coding region.

PMID- 14673708
TI  - An ab initio study of di- and trifluorobenzene-benzene complexes as relevant to
      carbonic anhydrase II-drug interactions.
AB  - Ab initio calculations at the MP2/6-31G* level have shown that variously
      substituted di- and trifluorobenzenes form non-covalent complexes with benzene
      that adopt either aromatic-aromatic or H--F binding, the choice being determined
      by the pattern of fluorination. The binding energies of these structures are from
      3.4 to 4.5 kcal mol(-1). This range is large enough to account for observed
      variations in the binding affinity of a library of fluoroaromatic inhibitors of
      carbonic anhydrase. This enzyme has an aromatic amino acid at a central position
      in the active site. The diverse modes of binding of the dimers also suggest that
      aggregates of fluorobenzenes might adopt specified 3-dimensional shapes in the
      solid state.

PMID- 14673713
TI  - Effect of phosphate on bacterioferritin-catalysed iron(II) oxidation.
AB  - The iron(III) mineral cores of bacterioferritins (BFRs), as isolated, contain a
      significant component of phosphate, with an iron-to-phosphate ratio approaching
      1:1 in some cases. In order to better understand the in vivo core-formation
      process, the effect of phosphate on in vitro core formation in Escherichia coli
      BFR was investigated. Iron cores reconstituted in the presence of phosphate were
      found to have iron-to-phosphate ratios similar to those of native cores, and
      possessed electron paramagnetic resonance properties characteristic of the
      phosphate-rich core. Phosphate did not affect the stoichiometry of the initial
      iron(II) oxidation reaction that takes place at the intrasubunit dinuclear iron
      binding sites (phase 2 of core formation), but did increase the rate of
      oxidation. Phosphate had a more significant effect on subsequent core formation
      (the phase 3 reaction), increasing the rate up to five-fold at pH 6.5 and 25
      degrees C. The dependence of the phase 3 rate on phosphate was complex, being
      greatest at low phosphate and gradually decreasing until the point of saturation
      at approximately 2 mM phosphate (for iron(II) concentrations <200 microM).
      Phosphate caused a significant decrease in the absorption properties of both
      phase 2 and phase 3 products, and the phosphate dependence of the latter mirrored
      the observed rate dependence, suggesting that distinct iron(III)-phosphate
      species are formed at different phosphate concentrations. The effect of phosphate
      on absorption properties enabled the observation of previously undetected events
      in the phase 2 to phase 3 transition period.

PMID- 14673714
TI  - Axial ligand complexes of the Rhodnius nitrophorins: reduction potentials,
      binding constants, EPR spectra, and structures of the 4-iodopyrazole and
      imidazole complexes of NP4.
AB  - Previously, we utilized 4-iodopyrazole (4IPzH) as a heavy atom derivative for the
      initial solution of the crystal structure of the nitrophorin from Rhodnius
      prolixus, NP1, where it was found to bind to the heme with the iodo group
      disordered in two positions. We have now determined the structure of the 4IPzH
      complex of NP4 at pH 7.5 and find that the geometry and bond lengths at the iron
      center are extremely similar to those of the imidazole (ImH) complex of the same
      protein (structure determined at pH 5.6), except that the G-H loop is not in the
      closed conformation. 4IPzH binds to the heme of NP4 in an ordered manner, with
      the iodo substituent pointed toward the opening of the heme pocket, near the
      surface of the protein. In order to understand the solution chemistry in terms of
      the relative binding abilities of 4IPzH, ImH, and histamine (Hm, a physiological
      ligand for the nitrophorins), we have also investigated the equilibrium binding
      constants and reduction potentials of these three ligand complexes of the four
      Rhodnius nitrophorins as a function of pH. We have found that, unlike the other
      Lewis bases, 4IPzH forms less stable complexes with the Fe(III) than the Fe(II)
      oxidation states of NP1 and NP4, and similar stability for the two oxidation
      states of NP2 and NP3, suggesting that this ligand is a softer base than ImH or
      Hm, for both of which the Fe(III) complexes are more stable than those of Fe(II)
      for all four nitrophorins. Surprisingly, in spite of this and the much lower
      basicity of 4IPzH than imidazole and histamine, the EPR g-values of all three
      ligand complexes are very similar.

PMID- 14673715
TI  - Quantitative three-dimensional anatomy of cervical, thoracic and lumbar vertebrae
      of Chinese Singaporeans.
AB  - This paper details the quantitative three-dimensional anatomy of cervical,
      thoracic and lumbar vertebrae (C3-T12) of Chinese Singaporean subjects based on
      220 vertebrae from 10 cadavers. The purpose of the study was to measure the
      linear dimensions, angulations and areas of individual vertebra, and to compare
      the data with similar studies performed on Caucasian specimens. Measurements were
      taken with the aid of a three-dimensional digitiser. The means and standard
      errors for linear, angular and area dimensions of the vertebral body, spinal
      canal, pedicle, and spinous and transverse processes were obtained for each
      vertebra. Compared to the Caucasian data, all the dimensions were found to be
      smaller. Of significance were the spinal canal area, and pedicle width and
      length, which were smaller by 31.7%, 25.7% and 22.1% on average, respectively. A
      slight divergence, instead of convergence, was found from T8 to T12. According to
      the findings, the use of a transpedicle screw may not be feasible. The results
      can also provide more accurate modelling for analysis and design of spinal
      implants and instrumentations, and also allow more precise clinical diagnosis and
      management of the spine in Chinese Singaporeans.

PMID- 14673716
TI  - Atlanto-occipital dislocation: four case reports of survival in adults and review
      of the literature.
AB  - Traumatic atlanto-occipital dislocation (AOD) is a rare cervical spine injury and
      in most cases fatal. Consequently, relatively few case reports of adult patients
      surviving this injury appeared in the literature. We retrospectively report four
      patients who survived AOD injury and were treated at our institution. A young man
      fell from height and a woman was injured in a traffic accident. Both patients
      survived the injury but died later in the hospital. The third patient had a
      motorcycle accident and survived with incomplete paraplegia. The last patient, a
      man involved in a working accident, survived without neurological deficit of the
      upper extremities. Rigid posterior fixation and complete reduction of the
      dislocation were applied in last two cases using Cervifix together with a
      cancellous bone grafting. Previously reported cases of patients surviving AOD are
      reviewed, and clinical features and operative stabilisation procedures are
      discussed.

PMID- 14673718
TI  - Secretin, 100 years later.
AB  - One hundred years have elapsed since the discovery of secretin by Bayliss and
      Starling in 1902. In the past century, the research of secretin has gone by many
      milestones including isolation, purification and structural determination,
      chemical synthesis, establishment of its hormonal status by radioimmunoassay and
      immunoneutralization, identification of the specific receptor, cloning of
      secretin and its receptor, and identification of a secretin-releasing peptide. It
      has become clear that secretin is a hormone-regulating pancreatic exocrine
      secretion of fluid and bicarbonate, gastric acid secretion, and gastric motility.
      The release and actions of secretin is regulated by hormone-hormonal and
      neurohormonal interactions. The vagus nerve, particularly its afferent pathway,
      plays an essential role in the physiological actions of secretin. Substantial
      information about the property of the secretin receptor has been accumulated, but
      a potent secretin receptor-specific antagonist remains to be formulated. The
      neural regulatory mechanisms of the release and action of secretin await further
      elucidation. The physiological role of secretin in intestinal secretions and
      motility and extragastrointestinal organs remains to be defined. The presence of
      secretin and its receptor in the central nervous system is well documented, but
      its function as a neuropeptide has been recognized gradually and requires
      extensive study in the future.

PMID- 14673717
TI  - Comparison of instrumented anterior interbody fusion with instrumented
      circumferential lumbar fusion.
AB  - Posterior lumbar interbody fusion (PLIF) restores disc height, the load bearing
      ability of anterior ligaments and muscles, root canal dimensions, and spinal
      balance. It immobilizes the painful degenerate spinal segment and decompresses
      the nerve roots. Anterior lumbar interbody fusion (ALIF) does the same, but could
      have complications of graft extrusion, compression and instability contributing
      to pseudarthrosis in the absence of instrumentation. The purpose of this study
      was to assess and compare the outcome of instrumented circumferential fusion
      through a posterior approach [PLIF and posterolateral fusion (PLF)] with
      instrumented ALIF using the Hartshill horseshoe cage, for comparable degrees of
      internal disc disruption and clinical disability. It was designed as a
      prospective study, comparing the outcome of two methods of instrumented interbody
      fusion for internal disc disruption. Between April 1994 and June 1998, the senior
      author (N.R.B.) performed 39 instrumented ALIF procedures and 35 instrumented
      circumferential fusion with PLIF procedures. The second author, an independent
      assessor (S.M.), performed the entire review. Preoperative radiographic
      assessment included plain radiographs, magnetic resonance imaging (MRI) and
      provocative discography in all the patients. The outcome in the two groups was
      compared in terms of radiological improvement and clinical improvement, measured
      on the basis of improvement of back pain and work capacity. Preoperatively,
      patients were asked to fill out a questionnaire giving their demographic details,
      maximum walking distance and current employment status in order to establish the
      comparability of the two groups. Patient assessment was with the Oswestry
      Disability Index, quality of life questionnaire (subjective), pain drawing,
      visual analogue scale, disability benefit, compensation status, and psychological
      profile. The results of the study showed a satisfactory outcome (score< or =30)
      on the subjective (quality of life questionnaire) score of 71.8% (28 patients) in
      the ALIF group and 74.3% (26 patients) in the PLIF group (P>0.05). On
      categorising Oswestry Index scores into "excellent", "better", "same", and
      "worse", we found no difference in outcome between the two groups: 79.5% (n=31)
      had satisfactory outcome with ALIF and 80% (n=28) had satisfactory outcome with
      PLIF. The rate of return to work was no different in the two groups. On
      radiological assessment, we found two nonunions in the circumferential fusion
      (PLIF) group (94.3% fusion rate) and indirect evidence of no nonunions in the
      ALIF group. There was no significant difference between the compensation rate and
      disability benefit rate between the two groups. There were three complications in
      ALIF group and four in the PLIF (circumferential) group. On the basis of these
      results, we conclude that it is possible to treat discogenic back pain by
      anterior interbody fusion with Hartshill horseshoe cage or with circumferential
      fusion using instrumented PLIF.

PMID- 14673719
TI  - Esophageal motility in Japanese patients with Barrett's esophagus.
AB  - BACKGROUND: The prevalence of gastroesophageal reflux disease has been increasing
      in Japan as it has in Western countries, but Barrett's esophagus (BE) is less
      common in Japan than in Western countries. The aim of this study, therefore, was
      to investigate esophageal motility and clinical characteristics in Japanese
      patients with BE. METHODS: Ten patients with BE were compared with ten patients
      with mild reflux esophagitis (RE), ten patients with severe RE, and ten healthy
      subjects of comparable age and sex. The prevalence of Helicobacter pylori was
      investigated in the patients with BE. The intraluminal microtransducer method was
      used to test for esophageal motility. Basal lower esophageal sphincter (LES)
      pressure was assessed by the rapid pull-through method. The esophageal wave after
      ten repeated 5-ml water swallowings at 30-s intervals was measured at 3, 8, 13,
      and 18 cm above the LES. RESULTS: The basal LES pressure, the amplitude of the
      esophageal wave at 3 and 8 cm above the LES, and the frequency of primary
      peristalsis in the severe RE group and BE group were significantly lower than the
      values in the healthy subjects and the mild RE group. The amplitude of the
      esophageal wave 13 cm above the LES in the BE group was significantly lower than
      that in the healthy subjects and the mild RE group. There was no difference
      between the severe RE group and the BE group in the basal LES pressure and the
      amplitude of the esophageal wave. The frequency of primary peristalsis in the BE
      group, however, was significantly lower than that in the severe RE group. Nine of
      the ten patients with BE were H. pylori-negative. CONCLUSIONS: Our conclusions
      are that esophageal dysmotility in Japanese patients with BE represents an
      advanced stage of severe RE, and that most Japanese patients with BE are H.
      pylori-negative.

PMID- 14673720
TI  - Symptomatic and endoscopic outcome of heartburn 3-4.5 years after starting
      lansoprazole therapy: a prospective study of 142 patients.
AB  - BACKGROUND: Heartburn is a common symptom with great impact on quality of life
      and on the economy. An approach that helps to alleviate patients' symptoms,
      decrease the burden on the economy, and improve longterm outcome is needed. Step
      down therapy, starting with the proton pump inhibitor lansoprazole, seems to
      achieve these goals. METHODS: All patients who were referred to the
      gastroenterology clinic at the University Health Center to evaluate their
      heartburn and who met the inclusion criteria were included in the present study.
      Symptomatic and endoscopic evaluations were carried out and then they were
      started on the proton pump inhibitor lansoprazole to achieve symptomatic control.
      Step-down therapy was carried out for these patients, provided their symptoms
      remained controlled. At the end of the study symptomatic and endoscopic outcomes
      were evaluated. RESULTS: Heartburn was controlled on lansoprazole 30 mg/per day
      in 76.1% of patients, and 18.3% required double this dose. Initial endoscopy
      showed normal findings in 38.7%, while 61.3% showed various grades of esophagitis
      including 1.4% with Barrett's epithelium. Of 119 patients who completed the
      study, 17 were non-compliant to therapy, 52 were controlled on minimal therapy,
      42 required lansoprazole to be kept symptom-free, and 8 patients had surgery.
      Endoscopic esophagitis was healed or attenuated in all compliant patients. No new
      cases of Barrett's appeared during follow up. CONCLUSIONS: Most of the patients
      with heartburn can be controlled on proton pump inhibitors, with improvement in
      the grade of endoscopic esophagitis. Half of these patients can be kept on
      minimal therapy after a period of 3-4.5 years with maintenance of improvement,
      while the remainder still need proton pump inhibitors for control.

PMID- 14673721
TI  - Spraying of phenol red dye as a screening test for Helicobacter pylori infection
      in surgically resected stomach specimens.
AB  - BACKGROUND: Endoscopic spraying of phenol red dye and urea (phenol red test) has
      recently been used to assess the distribution of Helicobacter pylori in the
      gastric mucosa. We examined whether the phenol red test could be used to detect
      H. pylori in surgically resected stomachs. METHODS: A total of 82 surgically
      resected stomachs, obtained from 82 patients (mean age, 60.1 years; range, 33-84
      years) with early gastric carcinomas were examined. Phenol red solution and urea
      were sprayed over the entire mucosa of each resected stomach. A color change from
      yellow to red was considered as a positive reaction for H. pylori. Gastric
      mucosal specimens taken from positively stained and negatively stained areas on
      the phenol red test were then examined immunohistochemically to determine the
      degree of H. pylori colonization. RESULTS: Diffusely positive reactions were seen
      in 16 resected stomachs (19%), and regionally positive reactions were seen in 36
      (44%). The other 30 stomachs (37%) showed no color change (negative reaction). H.
      pylori was detected immunohistochemically significantly more frequently in
      positively stained than in negatively stained areas ( P << 0.0001). Specificity,
      sensitivity, and predictive values for positive and negative results of the
      phenol red test, determined on the basis of H. pylori immunostaining, were 100%,
      74.3%, 100%, and 72.7%, respectively. CONCLUSIONS: The phenol red test is a
      specific, relatively sensitive, rapid, easy-to-use, and repeatable method that
      can be used to diagnose H. pylori infection in surgically resected material. It
      enables pathologists as well as gastroenterologists with no microbiological
      expertise to easily diagnose H. pylori infection.

PMID- 14673722
TI  - Interspousal transmission of hepatitis C in Thailand.
AB  - BACKGROUND: Previous studies evaluating the possibility of interspousal sexual
      transmission of hepatitis C virus (HCV) have yielded many conflicting results.
      Our study was carried out to determine the exact potential and risk factors of
      interspousal HCV transmission. METHODS: The spouses (54 men and 106 women; mean
      age +/-SD, 48 +/- 8 years) of 160 patients with HCV infection (106 men and 54
      women) were serologically tested for HCV using a third-generation enzyme-linked
      immuno- sorbent assay (ELISA). Positive results were confirmed by reverse
      transcriptase polymerase chain reaction (RT-PCR). For positive couples, the
      cluster nucleotides of the HCV gene and genotypes were compared on the basis of
      restriction fragment length polymorphism (RFLP), Innogenetic Line Probe Assay
      (INNO-LiPA), and direct sequencing. Similarly, phylogenetic tree and sequence
      homology analysis was performed in order to precisely verify interspousal
      transmission. Risk factors promoting interspousal HCV transmission were also
      identified. RESULTS: Throughout a mean duration of exposure of 23 + 5 years, most
      of the 160 partners had their usual and unprotected sexual relationships with the
      index patients. HCV-associated antibodies and HCV-RNA were detected in only 3
      (1.88%) of the 160 spouses. Furthermore, homology and phylogenetic tree analysis
      could not clearly demonstrate that any one of these 3 positive spouses was
      infected with the same strain of HCV as that identified in the index cases.
      Because a positive group remained elusive, risk factors of interspousal HCV
      transmission could not be determined in this study. CONCLUSIONS: According to
      this study, interspousal transmission of HCV seems to be very rare. HCV-positive
      spouses should be firmly reassured that they can maintain their normal marital
      life.

PMID- 14673723
TI  - Esophagogastric varices as a prognostic factor for the determination of clinical
      stage in patients with primary biliary cirrhosis.
AB  - BACKGROUND: Primary biliary cirrhosis (PBC) is usually classified as either
      asymptomatic PBC (a-PBC) or symptomatic PBC (s-PBC). Although the proportion of a
      PBC versus s-PBC patients has been consistently increasing, it is not clear
      whether the present criteria for the staging of PBC are optimal or not. We
      investigated the clinical stage of PBC patients from the standpoint of
      esophagogastric varices (EGV). METHODS: One hundred and nine PBC patients were
      enrolled in this retrospective study. We investigated the clinical features of
      PBC based on laboratory data, histological stage, symptoms, and existence of EGV.
      In addition, the clinical course and prognosis in patients who were periodically
      followed up were also studied. RESULTS: (1) EGV was detected in a-PBC patients,
      and there was no difference in the grade of EGV between a-PBC and s-PBC patients.
      (2) a-PBC patients with EGV had more liver damage than those without EGV, and a
      PBC patients with EGV had a poorer prognosis than those without EGV. (3) Three of
      11 patients who progressed from a-PBC to s-PBC within 3 years had EGV. (4) One of
      3 a-PBC patients with EGV had progressed to s-PBC at 3-year follow-up.
      CONCLUSIONS: These results indicate that EGV is one of the most important factors
      for evaluating PBC. Therefore, we would like to propose that a-PBC patients with
      EGV should either be included in the presently defined s-PBC class, or that new
      prognostic classes of PBC be created that include EGV as a prognostic factor.

PMID- 14673724
TI  - Percutaneous ultrasound-guided radiofrequency ablation with artificial pleural
      effusion for hepatocellular carcinoma in the hepatic dome.
AB  - BACKGROUND: Nodules of hepatocellular carcinoma (HCC) located in the hepatic dome
      cannot be depicted on ultrasography because of pulmonary air. Therefore,
      percutaneous treatment is not possible in such cases. The purpose of this study
      was to clarify the feasibility and safety of percutaneous sonographically guided
      radiofrequency (RF) ablation with the concurrent use of artificial pleural
      effusion for HCC located in the right subphrenic region. METHODS: Between May
      2001 and June 2002, 24 patients with 28 HCC nodules located directly below the
      diaphragm were enrolled in this study. The patient population included 17 men and
      7 women (age range, 51-87 years; mean age, 66.5 years). The maximum diameter of
      the HCC nodules ranged from 1.0 cm to 4 cm (mean +/- SD, 2.1 +/- 0.8 cm).
      RESULTS: We infused 200-1100 ml of 5% glucose solution intrathoracically to
      separate the lung and liver; thus, obtaining an image of the whole tumor was
      impossible on gray-scale sonography. Complete tumor necrosis was achieved in a
      single session of RF ablation in 27 (96.4%) of the 28 lesions, while two sessions
      of RF ablation were required for the remaining lesion (3.6%). During treatment,
      no dyspnea or other complications concerned with the respiratory system were
      observed. Clinical courses have been satisfactory without recurrences at 1-13
      months after treatment (mean, 7.9 months). CONCLUSIONS: Percutaneous RF ablation
      with artificial pleural effusion in patients with HCC in the hepatic dome may be
      a safe and feasible therapy.

PMID- 14673725
TI  - Prevention of gallstones by ursodeoxycholic acid after cardiac surgery.
AB  - BACKGROUND: One of the problems in prosthetic-valve recipients is the development
      of gallstones. We suggested that the use of a heart-lung machine may be closely
      related to gallstone formation. The objective of this study was to clarify the
      efficacy of ursodeoxycholic acid (UDCA) in the prevention of gallstone formation
      after open cardiac surgery. METHODS: One hundred and six patients without
      gallstones who underwent cardiac surgery in which a heart-lung machine was used
      were randomly divided into two groups: group A, comprising 54 patients who did
      not receive UDCA, and group B, comprising 52 patients who received UDCA (600 mg
      daily for 6 months from 1 week before surgery). Both groups were followed by
      ultrasonography for 60 months. Blood markers of hemolysis (hemoglobin,
      reticulocyte count, haptoglobin, total bilirubin, and lactate dehydrogenase) were
      evaluated before, immediately after, and at 3 weeks and 3, 6, 12, 24, and 60
      months after surgery. RESULTS: In groups A and B, cumulative incidence rates for
      gallstone formation were 15.1% and 0% at 3 months, 23.0% and 0% at 6 months,
      29.2% and 2.0% at 12 months, 29.2% and 8.4% at 24 months, and 29.2% and 8.4% at
      60 months, respectively. In regard to the composition of the gallstones, they
      were considered to be mainly black pigment stones. CONCLUSIONS: The prophylactic
      administration of UDCA resulted in a significant decrease in the incidence of
      gallstones after open cardiac surgery.

PMID- 14673726
TI  - The buried bumper syndrome: migration of internal bumper of percutaneous
      endoscopic gastrostomy tube into the abdominal wall.
AB  - A percutaneous endoscopic gastrostomy tube was inserted in a 59-year-old man who
      was undergoing craniotomy due to subarachnoid hemorrhage, because it was
      estimated that he could not have oral intake for a period of 4 weeks. Seventy
      days after the insertion, the percutaneous endoscopic gastrostomy tube was
      replaced because of its accidental removal by the patient. Two months after the
      second insertion, the tube had to be replaced due to nonfunctioning. The buried
      bumper syndrome was diagnosed on physical examination, and was confirmed by
      endoscopy, with findings of mucosal dimpling and nonvisualization of the internal
      bumper. The tube was removed by external traction without any abdominal incision,
      and the same site was used for the insertion of a replacement tube over a
      guidewire. The patient remained symptom-free during 18 months of follow-up.

PMID- 14673727
TI  - Mesenteric pseudocyst of the sigmoid colon.
AB  - A 31-year-old woman with right lower abdominal pain was hospitalized. Palpation
      revealed both tenderness and rebound tenderness in the right lower quadrant of
      her abdomen. Abdominal ultrasonography (US) indicated a multilocular cystic mass
      on the right side of the pelvic area, and a computed tomography (CT) scan showed
      a low-density mass measuring 7 cm in diameter. Torsion of the pedicle of a right
      ovarian cyst was suspected, and emergency laparotomy was performed. At operation,
      however, the uterus and both ovaries appeared normal, and exploration revealed a
      yellow-reddish cystic mass, approximately 10 cm in size, in the subserosa of the
      sigmoid colon. The mass was excised together with a 10-cm segment of the sigmoid
      colon. Macroscopically, it was a multilocular cyst, measuring 10 x 10 cm in size,
      and it contained white gelatinous fluid. Histological examination showed the cyst
      wall to be composed of neutrophils, lymphocytes, fibrin, and fibroblasts, but
      neither a specific endothelial lining nor proliferating lining was detected. The
      final pathological diagnosis was a mesenteric pseudocyst. Mesenteric pseudocysts
      are rare, and only 14 cases have been reported previously in the Japanese
      literature. Emergency operation was performed in 3 patients, including our own.
      The etiology of these three pseudocysts (manifested by acute abdomen) was
      unknown. We suspect that inflammation spread and injured lymph vessels, causing
      lymph to leak out and pool under the subserosal layer.

PMID- 14673728
TI  - Patients with severe liver cirrhosis followed up by L-[1-(13)C] phenylalanine
      breath test.
AB  - Compared to healthy subjects, patients with severe liver cirrhosis (LC) are
      reported to show lower values in the L-[1-(13)C] phenylalanine breath test (PBT).
      We performed this test several times during the clinical course in two patients
      with severe liver cirrhosis (LC). Patient 1 was a 67-year-old woman with non-B,
      non-C LC and hepatocellular carcinoma (HCC) in the lateral hepatic segment.
      Because the patient wanted to receive nonsurgical treatment for HCC,
      intraarterial administration of zinostatin stimalamer was performed. The patient
      was hospitalized four times before her death from liver failure on December 20,
      2000. During her clinical course, PBT was performed four times. Values for both
      the rate of hepatic phenylalanine oxidation (%(13)C dose h(-1)) and %(13)C
      cumulative excretion gradually decreased during her clinical course. Patient 2
      was a 57-year-old man with hepatitis C virus (HCV)-positive LC. He was
      hospitalized seven times between December 1998 and his death on May 24, 2001.
      During his clinical course, PBT was performed four times. Values for both %(13)C
      dose h(-1) and %(13)C cumulative excretion decreased during his clinical course.
      We confirmed that PBT was useful for following the course of LC.

PMID- 14673730
TI  - Intrahepatic sarcomatoid cholangiocarcinoma.
AB  - A 69-year-old woman was admitted to our hospital with fever and abdominal pain in
      the epigastric region. Abdominal ultrasonography demonstrated a well-defined
      hypoechoic mass in the epigastric region with encasement of the left hepatic lobe
      and stomach. Computed tomography confirmed a low-density mass, 20 cm in diameter,
      with enhancing peripheral areas. Angiography revealed the tumor to be
      hypovascular. After admission, the patient had a persistent fever and anemia that
      required transfusions of concentrated red blood cells. On the twelfth day after
      admission, she suffered disseminated intravascular coagulation and underwent an
      emergency operation. A lateral segmentectomy with dissection of lymph nodes,
      cholecystectomy, and hemigastrectomy were carried out. The size of the tumor was
      22 x 17 x 15 cm. Macroscopically, a cross-section revealed massive necrosis with
      hemorrhage. Histological examination of the tumor showed a malignant neoplasm
      with a carcinomatous component and a sarcomatous component, which were partly
      intermingled. The former consisted of moderately differentiated adenocarcinoma,
      while the latter consisted of pleomorphic spindle cells. Immunohistochemical
      examination of the sarcomatous component showed positive staining for vimentin,
      epithelial membrane antigen, and cytokeratin. The tumor was diagnosed as
      cholangiocarcinoma with extensive sarcomatous changes, based on these
      histological and immunohistochemical findings. The patient had an uneventful
      postoperative course. However, she died 3 months after surgery from dissemination
      of the carcinoma. The literature on this rare disease is reviewed and discussed.

PMID- 14673729
TI  - Spindle cell carcinoma of the intrahepatic bile duct in a patient with primary
      sclerosing cholangitis.
AB  - We present a case of spindle cell carcinoma of the intrahepatic bile duct that
      developed in a 34-year-old man with primary sclerosing cholangitis. At the time
      of presentation, the patient had a 10-year history of primary sclerosing
      cholangitis. A mass was found in the hepatic hilus and was resected surgically.
      The tumor was composed predominantly of spindle cells, and a small portion of the
      tumor appeared to be adenocarcinomatous by histology. Histological and
      immunohistochemical findings suggested that the spindle cells were epithelial in
      origin; thus, this tumor was identified as a spindle cell carcinoma. Spindle cell
      carcinomas arising in the bile duct are extremely rare. Furthermore, the
      coexistence of spindle cell carcinoma and primary sclerosing cholangitis has not
      been reported thus far. We were able to follow up the entire course of this rare
      case. In this case report, we describe the clinicopathological findings of this
      case and review the literature concerning this type of tumor.

PMID- 14673731
TI  - Abnormal arrangement of the pancreato-biliary ductal system associated with
      advanced gallbladder cancer diagnosed 3 years after follow-up ultrasonography.
AB  - We herein report a case of abnormal arrangement of the pancreato-biliary ductal
      system (AAPB) followed by advanced gallbladder cancer 9 years after the initial
      endoscopic retrograde cholangiopancreatography (ERCP) diagnosis and almost 3
      years after follow-up ultrasonography (US). A 65-year-old woman was referred to
      our department from a private clinic because of difficulty in controlling her
      diabetes mellitus. The patient had no complaints, and physical examination
      revealed no jaundice in her skin or conjunctiva. ERCP demonstrated the presence
      of AAPB (bile duct-main type) without congenital dilatation of the bile duct or
      irregularity in the gallbladder wall. She did not wish to undergo
      cholecystectomy. Follow-up transabdominal US revealed no change in the
      gallbladder. Two years and 9 months after this US examination, she developed
      advanced gallbladder cancer involving the liver and bile duct, with paraaortic
      lymph node metastases confirmed by US, computed tomography, and ERCP. This case
      re-emphasizes the necessity for patients with AAPB to undergo intensive follow-up
      examinations or cholecystectomy when the diagnosis of AAPB has been established.

PMID- 14673732
TI  - Characteristics of clinicopathological and histological findings of superficial
      depressed type of colorectal submucosal invasive carcinoma, compared with polyp
      type.

PMID- 14673733
TI  - Toxic megacolon associated with cytomegalovirus infection in ulcerative colitis.

PMID- 14673734
TI  - Treatment of esophagitis/vagitis-induced paroxysmal atrial fibrillation by proton
      pump inhibitors.

PMID- 14673735
TI  - Are esophagogastric varices a late manifestation in primary biliary cirrhosis?

PMID- 14673736
TI  - Prevention of black pigment gallstone formation after cardiac surgery by
      ursodeoxycholic acid.

PMID- 14673737
TI  - [Health care research is necessary!].

PMID- 14673738
TI  - [Prevalence of diabetes mellitus in Germany 1998-2001. Secondary data analysis of
      a health insurance sample of the AOK in Hesse/KV in Hesse].
AB  - AIMS: The aim of this population-based study was to assess the prevalence of
      subjects with diabetes mellitus by retrospectively analysing routine health
      insurance data. METHODS: This analysis comprised a 18.75% random sample of all
      members of the largest regional statutory health insurance (Allgemeine
      Ortskrankenkasse, AOK) in Hesse. Patients with diabetes were identified by
      criteria such as ICD-10 diagnoses and regular prescriptions of insulin and oral
      antidiabetic agents. The data were corrected for the age and gender distribution
      of the German population. RESULTS: Over the 4-year observation period there was a
      continuous increase in the prevalence of subjects with known diabetes mellitus,
      from 7.24% in 1998 to 8.79% in 2001. After correction for the German population
      the last figure corresponded to a prevalence rate of 6.00% in 1998 and 6.91% in
      2001. During this period, there was an overproportional increase in the
      percentage of subjects treated with insulin, from 1.49% in 1998 to 1.91% in 2001,
      while there was only a moderate increase in the percentage of subjects under oral
      medication and under dietary treatment, respectively. In the age group of 70 and
      above roughly 25% of all subjects had known diabetes. In this age group, more
      than 6% of all people were treated with insulin. CONCLUSIONS: This data suggests
      that there was a continuous increase in the prevalence of individuals treated for
      diabetes between 1998 and 2001 in Germany by approximately 5% per year. After
      correction for the total German population the pre-valence of diagnosed diabetes
      is nearly 7%.

PMID- 14673739
TI  - [Outpatient care of patients with diabetes mellitus in 2001. Analysis of a health
      insurance sample of the AOK in Hesse/KV in Hesse].
AB  - AIM: Aim of this retrospective case-control study was to assess the quality of
      out-patient care in patients with diabetes mellitus by analysing health insurance
      data from a large cohort of members of a regional statutory health insurance fund
      in Hesse. METHODS: The study was carried out in the 'Versichertenstichprobe AOK
      Hessen/KV Hessen', a 18.75% random sample of the AOK Hesse, for the year 2001
      corresponding to 306,736 subjects and 26,972 diabetics. All medical services and
      prescriptions provided by primary-care physicians were documented. RESULTS:
      Compared to an age- and sex-matched control group patients with diabetes received
      more out-patient medical services (diabetics: 126 +/- 0.8, controls: 76 +/- 0.4
      per year, p < 0.0001) and more prescriptions (diabetics: 39.9 +/- 0.3, controls:
      20.0 +/- 0.3 per year, p < 0.0001) in 2001. HbA (1c) measurements were performed
      in 69.5% of the insulin-treated patients, in 64.3% of the patients under
      monotherapy with oral hypoglycaemic agents and in 41.1% of the patients under
      dietary treatment. 78.1% of the insulin-treated patients, 12.0% of those under
      oral hypoglycaemic agents and 2.0% of patients under dietary treatment received
      prescriptions for material for blood glucose self-monitoring. In contrast, a
      retinal examination was performed in only 45.8%, 31.1% and 22.5% of the patients
      in the three treatment groups throughout the year. The respective figures for
      screening for microalbuminuria in the three treatment groups were 12.7%, 7.1% and
      3.6%. CONCLUSIONS: The results of this retrospective analysis suggest that the
      out-patient medical care of subjects with diabetes is in some respect
      unsatisfactory and does not comply with the accepted recommendations for
      appropriate diabetes care.

PMID- 14673740
TI  - [Osteomalacia with fatal outcome in an elderly patient].
AB  - HISTORY AND ADMISSION FINDINGS: A 63-year-old woman was admitted with diffuse
      bone pain, chest deformity and orthopnea. She had previous prolonged periods of
      bed rest and decreased sunlight exposure after several bone fractures.
      INVESTIGATIONS: Laboratory tests showed hypocalcemia, hypophosphatemia with
      secondary hyperparathyroidism. The 25-hydroxy-D-vitamin level was too low for
      measurement. Radiological investigations raised the possibility of metabolic bone
      disease with secondary fracture. (99m)Tc-MDP bone scintigraphy demonstrated
      pathological isotope accumulation in places typical for osteomalacia. The
      histological investigation of the bone showed a thickening of the osteoid
      substance. DIAGNOSIS, TREATMENT AND COURSE: Osteomalacia was diagnosed. Two weeks
      of administering of daily 3000 I.U. vitamin D and 1500 mg calcium normalised the
      serum level of calcium and phosphate. Because of orthopnea and bone pain the
      patient stayed in the bed, and had to be given her nadroparin calcium. After six
      weeks heart and respiratory failure occurred. The patient died from a subtotal
      pulmonary embolism, which was a consequence of a deep vein thrombosis of the leg.
      CONCLUSION: In elderly people chronic and serious vitamin D deficiency can cause
      a life-threatening condition which can be prevented by vitamin D and calcium
      administration.

PMID- 14673741
TI  - [Hepatic encephalopathy--case report].

PMID- 14673742
TI  - [Hepatic encephalopathy--diagnostics].

PMID- 14673743
TI  - [Hepatic encephalopathy--therapy].

PMID- 14673746
TI  - [Liability for diagnostic errors. Verdict of the Federal Supreme Court of August
      7, 2003--VI ZR 304/02].

PMID- 14673747
TI  - [Is "COMET" pointing in the right direction?--Pro].

PMID- 14673748
TI  - [Is "COMET" pointing in the right direction?--Con].

PMID- 14673749
TI  - [Can patients without coronary heart disease prevent a heart infarct with 30 or
      50 mg acetylsalicylic acid?].

PMID- 14673750
TI  - Ribosomal DNA sequencing and reinstatement of the genus Arthroascus von Arx.
AB  - Sequence analysis of the D1/D2 domain of 26S rDNA was conducted upon seven
      Arthroascus strains from different geographic localities. The European and Asian
      species Arthroascus schoenii was documented from the North-American continent and
      from the Island of Hawaii. We discuss the heterogeneity of the genus
      Saccharomycopsis sensu Kurtzman and Robnett 1995. On the basis of molecular and
      genetic data the genus Arthroascus von Arx is reinstated.

PMID- 14673751
TI  - Isolation and characterization of halophilic lactic acid bacteria isolated from
      "terasi" shrimp paste: a traditional fermented seafood product in Indonesia.
AB  - Lactic acid bacteria from "terasi" shrimp paste, a highly popular fermented
      seafood in Indonesia were isolated and characterized. Viable cell counts were
      10(4) to 10(6) cfu/g on MRS medium. All the isolates were catalase-negative, gram
      positive cocci and were able to grow at 15% NaCl. Numerical phenotypic analysis
      showed that the isolates clustered into one group. However, they could be
      classified into two types: the Tetragenococcus halophilus group and the T.
      muriaticus group as revealed by a restriction fragment length polymorphism (RFLP)
      analysis and sequencing of the 16S rRNA gene. This study is the first to show
      that both species of Tetragenococcus are distributed in Indonesian fermented
      foods.

PMID- 14673752
TI  - Cellular polyamines of the acidophilic, thermophilic and thermoacidophilic
      archaebacteria, Acidilobus, Ferroplasma, Pyrobaculum, Pyrococcus,
      Staphylothermus, Thermococcus, Thermodiscus and Vulcanisaeta.
AB  - Cellular polyamines of newly isolated acidophilic, thermophilic and
      thermoacidophilic archaebacteria were investigated for the chemotaxonomic
      significance of polyamine distribution profiles. In addition to spermidine,
      spermine and agmatine, a quaternary branched penta-amine, N(4)
      bis(aminopropyl)spermidine, was found in thermophilic Thermococcus waiotapuensis,
      Thermococcus aegaeus and Pyrococcus glycovorans belonging to the order
      Thermococcales. An acidophilic euryarchaeon, Ferroplasma acidiphilum located in
      the order Thermoplasmatales, contained spermidine and agmatine. Norspermidine,
      spermidine, norspermine and spermine were found in thermoacidophilic Acidilobus
      aceticus and thermophilic Thermodiscus maritimus located in the order
      Desulfurococcales, and in thermophilic Pyrobaculum arsenaticum, Pyrobaculum
      oguniense, Vulcanisaeta distributa and Vulcanisaeta souniana belonging to the
      order Thermoproteales; however, the four genera differ on their tetra- and penta
      amine levels. Thermophilic Staphylothermus hellenicus belonging to
      Desulfurococcales contained caldopentamine, caldohexamine and N1
      acetylcaldopentamine in addition to norspermidine, spermidine and norspermine.
      This is the first report on the occurrence of acetylated penta-amine in nature.

PMID- 14673753
TI  - Dioszegia changbaiensis sp. nov., a basidiomycetous yeast species isolated from
      northeast China.

PMID- 14673754
TI  - Diacetyl of lactic acid bacteria from milk and fermented foods in Thailand.

PMID- 14673755
TI  - Identification of pathogenic and non-pathogenic Vibrio strains from shrimp and
      shrimp farms in the Philippines.

PMID- 14673756
TI  - Surrogate markers of immune function in human immunodeficiency virus-infected
      patients: what are they surrogates for?

PMID- 14673757
TI  - Incomplete immune reconstitution after initiation of highly active antiretroviral
      therapy in human immunodeficiency virus-infected patients with severe CD4+ cell
      depletion.
AB  - Immune function was observed for 144 weeks in 643 human immunodeficiency virus
      (HIV)-infected subjects who (1) had nadir CD4+ cell counts of <50 cells/mm3,
      followed by a sustained increase to > or =100 cells/mm3 after the initiation of
      HAART, and (2) were enrolled in a randomized trial of continued azithromycin
      prophylaxis versus withdrawal for prevention of Mycobacterium avium complex
      disease. The median CD4+ cell count was 226 cells/mm3 at entry and 358 cells/mm3
      at week 144. Anergy (80.2% of patients) and lack of lymphoproliferative response
      to tetanus toxoid (TT; 73%) after immunization and impaired antibody responses
      after receipt of hepatitis A (54%) and TT (86%) vaccines were considered to be
      evidence of impaired immune reconstitution. Receipt of azithromycin did not have
      an effect on CD4+ cell count but was associated with higher rates of delayed-type
      hypersensitivity responses to TT (25% of subjects who received azithromycin vs.
      15% of those who did not; P=.009) and mumps skin test antigen (29% vs. 17%;
      P=.001). Although the subjects had only partial responses to immune function
      testing, the rate of opportunistic infections was very low, and none of the tests
      was predictive of risk.

PMID- 14673758
TI  - Granulocyte-macrophage colony-stimulating factor induces modest increases in
      plasma human immunodeficiency virus (HIV) type 1 RNA levels and CD4+ lymphocyte
      counts in patients with uncontrolled HIV infection.
AB  - BACKGROUND: Studies have reported that plasma human immunodeficiency virus type 1
      (HIV-1) RNA levels and CD4+ lymphocyte counts in HIV-infected patients improved
      after treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF).
      METHODS: In AIDS Clinical Trials Group Protocol 5041, 116 patients were enrolled
      in a double-blind, randomized, placebo-controlled clinical trial of 16 weeks of
      250 microg of GM-CSF administered subcutaneously 3 times/week, followed by open
      label treatment for an additional 32 weeks. Patients had stable baseline plasma
      HIV-1 RNA levels of > or =1500 copies/mL and received constant antiretroviral
      regimens through at least the first 16 weeks of the study. RESULTS: After 16
      weeks, the GM-CSF group tended to have greater, though clinically insignificant,
      increases in plasma HIV-1 RNA levels, compared with the placebo group (median
      change, +0.048 vs. -0.103 log copies/mL; P=.036, in a post hoc analysis). There
      were trends toward progressive modest increases in CD4+ lymphocyte counts with GM
      CSF treatment at 16 weeks (median change, +14 vs. -6 cells/mm3; P=.06) and
      beyond. CONCLUSIONS: GM-CSF does not have an antiviral effect in patients with
      ongoing HIV replication but may increase CD4+ lymphocyte counts.

PMID- 14673759
TI  - Reconstitution of hepatitis B virus (HBV)-specific T cell responses with
      treatment of human immunodeficiency virus/HBV coinfection.
AB  - Liver-related mortality is an increasing problem in human immunodeficiency virus
      (HIV)/hepatitis B virus (HBV)-coinfected patients receiving highly active
      antiretroviral therapy (HAART). In HIV-negative patients, HBV chronicity is
      associated with a reduction in specific T cell responses that can be partially
      restored by treatment with lamivudine. We studied 5 HIV/HBV-coinfected patients
      treated with HAART, either with or without addition of a drug with specific anti
      HBV activity. Our data show that reconstitution of some HBV-specific T cell
      responses can also occur in HIV-positive patients after a reduction in HBV load.
      This potential to recover T cell responses, which has been thought to be critical
      for HBV control, provides support for the addition of anti-HBV therapy in the
      treatment of HIV/HBV-coinfected patients.

PMID- 14673760
TI  - Increased human immunodeficiency virus loads in active methamphetamine users are
      explained by reduced effectiveness of antiretroviral therapy.
AB  - Abuse of methamphetamine (METH) is a frequent comorbidity among individuals
      infected with human immunodeficiency virus (HIV) type 1. In cell cultures and
      animal models, METH accelerates retroviral replication. To determine whether METH
      increases HIV replication in humans, we evaluated HIV loads in HIV-positive METH
      users and nonusers. We studied 3 groups: Tox+, active METH use and positive urine
      toxicology results; METH(+)Tox-, previous METH dependence/abuse and negative
      urine toxicology results; METH(-)Tox-, no METH dependence/abuse and negative
      urine toxicology results. Tox+ subjects' plasma virus loads were significantly
      higher than METH(+)Tox- and METH(-)Tox- subjects'; cerebrospinal fluid virus
      loads showed a similar but nonsignificant trend. Stratification by use of highly
      active antiretroviral therapy (HAART) revealed that virus loads were higher only
      in those Tox+ subjects who reported receiving HAART. In contrast, abstinent
      former METH abusers (METH(+)Tox-) receiving HAART effectively suppressed viral
      replication. These data suggest that abstinence programs are a key component of
      effective treatment of HIV in METH-abusing populations.

PMID- 14673761
TI  - Enfuvirtide (T-20) cross-reactive glycoprotein 41 antibody does not impair the
      efficacy or safety of enfuvirtide.
AB  - The present study investigated the effect of enfuvirtide cross-reactive
      glycoprotein 41 (gp41) antibody on the efficacy or safety of enfuvirtide in
      patients participating in 1 of 2 24-week phase 3 clinical trials (T-20 vs.
      optimized regimen only [TORO] 1 and TORO 2). Serum samples from human
      immunodeficiency virus-infected patients receiving enfuvirtide plus optimized
      background (OB) and from patients receiving OB only were evaluated for
      enfuvirtide cross-reactive gp41 antibodies. Most patients had detectable levels
      of antibody at baseline; 78% of patients treated with enfuvirtide plus OB had a >
      or =30% decrease in level of antibody, compared with 43% of patients treated with
      OB only. Baseline antibody status did not influence virological responses to
      enfuvirtide-containing treatment. Favorable virological responses were more
      common among patients who experienced a > or =30% decrease from baseline than
      among those who experienced either an increase or a lesser decrease. A decrease
      in virus load correlated with a decrease in level of antibody. Safety was
      unaffected by the presence of positive antibody at any time point or change in
      level of antibody. There was no evidence that enfuvirtide cross-reactive gp41
      antibody affects the efficacy or safety of enfuvirtide.

PMID- 14673762
TI  - Serum immunoglobulin A response to human papillomavirus type 16 virus-like
      particles in human immunodeficiency virus (HIV)-positive and high-risk HIV
      negative women.
AB  - Serum samples from 2008 human immunodeficiency virus (HIV)-positive and 551 HIV
      negative women were tested for immunoglobulin A (IgA) to human papillomavirus
      (HPV) type 16 capsids. IgA seropositivity was lower than previously reported IgG
      seropositivity (7% vs. 51%), but, like IgG antibodies, HPV 16 IgA was associated
      with sexual behavior, cervicovaginal HPV 16 DNA, and cytological abnormalities.
      IgA seropositivity was higher in HIV-positive women than in HIV-negative women
      (7.7% vs. 4.9%; P=.02), but the association was lost after adjustment for HPV 16
      cervicovaginal infection. IgA, but not IgG, seropositivity was associated with
      progression to high-grade cytological abnormalities (relative hazard [RH], 2.2
      [95% confidence interval, 1.2-4.2]), raising the possibility that an IgA response
      to HPV 16, as described for other DNA viruses, may be a marker of persistent
      viral replication. The risk of incident infection with non-16-related HPV types
      was increased in IgA seropositive women (RH, 1.8 [95% confidence interval, 1.3
      2.6]), compared with seronegative women (RH, 2.2 [95% confidence interval, 0.9
      5.4]), but there was no difference in the risk of incident HPV 16 or HPV 16
      related infections. This may be evidence of partial type-specific or clade
      specific immunity conferred by seropositivity to HPV 16 capsids.

PMID- 14673763
TI  - Persistence of vaccine-derived polioviruses among immunodeficient persons with
      vaccine-associated paralytic poliomyelitis.
AB  - To estimate long-term poliovaccine virus persistence among immunodeficient
      patients with vaccine-associated paralytic poliomyelitis (iVAPP), cases reported
      in the United States during 1975-1997 were reviewed, with subsequent follow-up
      and virological testing. Six (16.2%) of 37 subjects excreted poliovaccine viruses
      for > or =6 months. Partial genomic sequencing of their available poliovirus
      isolates showed considerable divergence from the prototype Sabin strain in all
      cases. Poliovirus persistence declined over time since the last oral poliovaccine
      dose: at 6 months, 19.4%; 1 year, 14.3%; 5 years, 4%; and 10 years, 0% (P<.05) of
      patients. Despite the high prevalence of poliovaccine virus persistence among
      patients with iVAPP, this group appears to be an unlikely source of poliovirus
      reintroduction in developed countries because of the rarity and high fatality
      rate of iVAPP and the possible spontaneous clearance of polioviruses. These
      results are important for developing "endgame" strategies for the Global
      Poliomyelitis Eradication Program.

PMID- 14673764
TI  - Epstein-Barr virus (EBV) early-antigen serologic testing in conjunction with
      peripheral blood EBV DNA load as a marker for risk of posttransplantation
      lymphoproliferative disease.
AB  - Epstein-Barr virus (EBV) early-antigen (EA) serologic profile was examined in
      conjunction with peripheral blood EBV DNA load, to assess its value in evaluating
      the risk of developing posttransplantation lymphoproliferative disease (PTLD).
      The cohort included 26 pediatric recipients of solid-organ transplants, 6 of whom
      developed PTLD. All 6 patients had high peripheral blood EBV DNA loads. Of the
      remaining 20 patients who did not develop PTLD, 14 had high EBV DNA loads, and 6
      had low EBV DNA loads. None of the patients who developed PTLD had significant EA
      immunoglobulin G (IgG) titers. However, all 14 patients with high EBV DNA loads
      and without PTLD had high EA IgG titers, either at the time of initial high EBV
      DNA load or during the ensuing weeks. Here, we report that EBV DNA load analysis,
      combined with EA serologic analysis, is a potentially useful prognostic marker
      for evaluating the risk of developing PTLD.

PMID- 14673765
TI  - High seroprevalence of human metapneumovirus among young children in Israel.
AB  - Exposure to the newly discovered human metapneumovirus (HMPV) during the first 2
      years of life was studied by longitudinal serological analysis in 40 healthy
      children in southern Israel. The seropositivity rate decreased to a minimum by
      age 13 months and increased to 52% by age 24 months. Evidence of new infection
      was detected in 13%, 23%, and 55% of children by ages 7, 13, and 24 months,
      respectively. The high exposure rates suggest that HMPV may be an important cause
      of community-acquired respiratory-tract infections in young children.

PMID- 14673766
TI  - Preconception vaccination with a glycoprotein B (gB) DNA vaccine protects against
      cytomegalovirus (CMV) transmission in the guinea pig model of congenital CMV
      infection.
AB  - DNA vaccines expressing the guinea pig cytomegalovirus (GPCMV) homologs of the
      glycoprotein B (gB) and UL83 proteins were evaluated for protection against
      congenital GPCMV infection. After 4 doses of DNA administered by epidermal (gene
      gun) route, all guinea pigs developed enzyme-linked immunosorbent assay (ELISA)
      antibody and, for gB-vaccine recipients, neutralizing antibody. Dams were
      challenged with 1 x 10(4) plaque-forming units of GPCMV in the third trimester.
      Preconception vaccination with gB did not decrease overall pup mortality,
      although, within the gB-vaccine group, pup mortality was lower among dams with
      high ELISA responses. Preconception maternal vaccination with gB vaccine
      significantly reduced congenital transmission in liveborn pups. In contrast, UL83
      vaccine had no significant effect on pup mortality or vertical transmission of
      GPCMV. Virus load was significantly lower in infected pups born to gB- and UL83
      vaccinated dams than in infected pups born to control dams. These data support
      the concept that subunit gB vaccination may be useful in protecting against CMV
      induced disease.

PMID- 14673767
TI  - Pathogenetic tropism of varicella-zoster virus to primary human hepatocytes and
      attenuating tropism of Oka varicella vaccine strain to neonatal dermal
      fibroblasts.
AB  - The pathogenesis of varicella-zoster virus (VZV) was characterized by the cell
      tropism of the original Oka and attenuated Oka varicella vaccine strains. Among
      the tissue cells examined, VZV replicated best in hepatocytes and second best in
      lung fibroblasts. The high affinity to hepatocytes and lung fibroblasts might
      correlate with varicella hepatitis and pneumonia and with autopsy observations of
      varicella. Cell tropism may be important in understanding the pathogenesis of
      VZV.

PMID- 14673768
TI  - Effect of drug resistance on the generation of secondary cases of tuberculosis.
AB  - BACKGROUND: The results of animal studies suggest that isoniazid-resistant
      strains of Mycobacterium tuberculosis are less pathogenic than isoniazid
      susceptible strains. Here, we assess the relative pathogenicity of drug-resistant
      and drug-susceptible strains, in a human population. METHODS: We linked IS6110
      genotype patterns of M. tuberculosis strains with drug-susceptibility test
      results and epidemiologic information for 85% of culture-positive incident cases
      of tuberculosis (TB) in San Francisco during 1991-1999. We assumed that drug
      susceptible and drug-resistant strains were transmitted to secondary case
      patients if the drug-resistance and genotype patterns were identical. We
      calculated the number of secondary cases for each drug-resistance pattern and
      determined the relative secondary-case rate ratio (SR) of drug-resistant TB to
      drug-susceptible TB. RESULTS: There were 1800 patients with culture-positive TB,
      drug-susceptibility test results, and genotyping results. The overall SR of drug
      resistant to drug-susceptible TB cases was 0.51 (95% confidence interval [CI],
      0.37-0.69). The SR was 0.29 (95% CI, 0.15-0.57) for isoniazid-resistant strains,
      0.10 (95% CI, 0.02-0.42) for strains resistant to both isoniazid and
      streptomycin, and 0.88 (95% CI, 0.53-1.47) for streptomycin-resistant strains.
      There were no secondary cases caused by multidrug-resistant (MDR) TB. The SR for
      rifampin-resistant cases was 2.33 (95% CI, 1.04-5.25). Seventy-eight percent
      (7/9) of the patients with rifampin-resistant secondary cases of TB were
      seropositive for human immunodeficiency virus. CONCLUSION: In the context of an
      effective TB program in San Francisco, strains that were resistant to isoniazid
      either alone or in combination with other drugs were less likely to result in
      secondary cases than were drug-susceptible strains. In this setting, isoniazid
      resistant and MDR TB cases were not likely to produce new, incident drug
      resistant TB cases.

PMID- 14673769
TI  - P fimbria-specific B cell responses in patients with urinary tract infection.
AB  - Local immune response may be important in defense against urinary tract infection
      (UTI). P fimbria, an important virulence factor of Escherichia coli, is a
      noteworthy candidate for use in a vaccine against pyelonephritis (PN). Eleven
      patients with PN and 14 patients with lower urinary tract infection (LUTI) caused
      by E. coli were studied for mucosa-derived antibody-secreting cells (ASCs) and
      for urinary antibodies. In the 10 patients with P-fimbriated (P+) E. coli, an ASC
      response to P fimbria was found in 5 of 5 patients who had PN and 1 of 5 patients
      who had LUTI. The response to P fimbria was stronger among patients with P+ PN
      than among patients with PN caused by non-P-fimbriated E. coli (P-) (P<.001) or
      patients with P+ LUTI (P<.001). The response to P fimbria was also stronger than
      the response to outer-membrane protein A among all patients with PN. P fimbria
      specific urinary immunoglobulin A antibody levels were higher among patients with
      P+ PN than those with P- PN. The results show a P fimbria-specific local immune
      response, which further encourages the use of P fimbria in locally administrable
      UTI vaccines.

PMID- 14673770
TI  - Cytolethal distending toxin: a potential virulence factor for Helicobacter
      cinaedi.
AB  - Although Helicobacter cinaedi is the most commonly reported enterohepatic
      helicobacter in humans, there are no reports of virulence factors, and little is
      known about how it infects and causes disease. In this study, H. cinaedi isolates
      from humans and animals were examined for production of cytolethal distending
      toxin (Cdt). Cdt causes distention in cells and arrest in the G2/M phase of cell
      division. It is encoded by three genes: cdtA, cdtB, and cdtC. cdtB is the most
      conserved. All isolates except the American Type Culture Collection strain
      (identified as H. fennelliae) demonstrated Cdt activity and had a cdtB polymerase
      chain-reaction product homologous with known cdtB. Deduced amino acid sequences
      of cdtB showed a high (93%-99%) degree of similarity among the H. cinaedi
      isolates. H. cinaedi shares the production of Cdt with other enteric pathogens,
      including enterohepatic Helicobacter species. This is the first report of a
      putative virulence factor in H. cinaedi.

PMID- 14673771
TI  - Structure and distribution of an unusual chimeric genetic element encoding
      macrolide resistance in phylogenetically diverse clones of group A Streptococcus.
AB  - The resistance of group A Streptococcus (GAS) to macrolide antibiotics is now a
      worldwide problem. Preliminary sequencing of the genome of an erythromycin
      resistant serotype M6 clone that was responsible for a pharyngitis outbreak in
      Pittsburgh, Pennsylvania, was conducted to determine the structure of the genetic
      element containing the mefA gene, which encodes a macrolide efflux protein. The
      mefA gene is associated with a 58.8-kb chimeric genetic element composed of a
      transposon inserted into a prophage. This element also encodes a putative
      extracellular protein with a cell-wall anchoring motif (LPKTG) located at the
      carboxyterminus. The mefA element was present in phylogenetically diverse GAS
      strains isolated throughout the United States. Culture supernatants, prepared
      after mitomycin C treatment, of a strain representing the outbreak clone
      contained mefA element DNA in a DNAse-resistant form. Together, these data
      provide new information about the molecular genetic basis of macrolide resistance
      and dissemination in GAS strains.

PMID- 14673772
TI  - PcrH of Pseudomonas aeruginosa is essential for secretion and assembly of the
      type III translocon.
AB  - Pseudomonas aeruginosa harbors a type III secretion system that translocates
      antihost effectors into an infected eukaryotic cell. PcrH is a key component of
      type III secretion in this essential virulence strategy. In the absence of PcrH,
      P. aeruginosa is translocation deficient because of a specific reduction in
      presecretory stability and subsequent secretion of PopB and PopD, 2 proteins
      essential for the translocation process. PcrH exerts this chaperone function by
      binding directly to PopB and PopD. Consistent with the genetic relatedness of
      PcrH with LcrH of pathogenic Yersinia species, these proteins are functionally
      interchangeable with respect to their ability to complement the translocation
      defect associated with either a lcrH or pcrH null mutant, respectively. Thus, the
      translocator class of chaperones performs a critical function in ensuring the
      assembly of a translocation competent type III secreton. Finally, unlike the
      regulatory roles of other translocator-class chaperones (e.g., LcrH, SicA of
      Salmonella enterica, and IpgC of Shigella species), in vitro regulation of P.
      aeruginosa type III secretion does not involve PcrH.

PMID- 14673773
TI  - Prevention of fatal Clostridium difficile-associated disease during continuous
      administration of clindamycin in hamsters.
AB  - Clostridium difficile-associated disease (CDAD) due to toxigenic strains is
      prevented in hamsters by colonization by nontoxigenic C. difficile after
      administration of clindamycin (Cm). To prevent CDAD during treatment with
      antibiotics, we gave a Cm-resistant nontoxigenic C. difficile strain, M13
      (minimal inhibitory concentration [MIC], >256 microg/mL), and a Cm-susceptible
      strain, M3 (MIC, 0.5 microg/mL), to hamsters receiving Cm daily for days 1-5.
      Either M13 or M3 was given orogastrically (1 x 10(6) spores/day) to each hamster
      in 3 groups of 5 each, on either day 3, days 3-5, or days 3-7. M13 colonized at a
      higher rate and faster than did M3 (P<.001). When hamsters were challenged by
      toxigenic strain B1 on days 5, 7, or 9, M13 prevented CDAD in 100% of the
      hamsters. M3 protected no hamsters challenged by B1 on day 5, 20% on day 7, and
      100% on day 9. M13 contains the erm(B) resistance gene but not the mobilizable
      element Tn5398. The benefits of use of Cm-resistant nontoxigenic C. difficile to
      prevent CDAD must be balanced against the risk that resistance might be
      transferred to other enteric bacteria.

PMID- 14673774
TI  - Effects of rhinovirus infection on the adherence of Streptococcus pneumoniae to
      cultured human airway epithelial cells.
AB  - To examine the effects of rhinovirus (RV) infection on the adherence of
      Streptococcus pneumoniae to human tracheal epithelial cells, cells were infected
      with RV-14, and S. pneumoniae were added to the culture medium. The number of S.
      pneumoniae adhering to epithelial cells increased after RV infection. Y-24180, a
      specific inhibitor of the platelet-activating factor receptor (PAF-R); PAF; and
      the pyrrolidine derivative of dithiocarbamate, an inhibitor of transcription
      factor nuclear factor-kappaB (NF-kappaB), decreased the number of S. pneumoniae
      adhering to cells after RV-14 infection. RV-14 infection increased PAF-R
      expression and the activation of NF-kappaB and promoter-specific transcription
      factor 1. These findings suggest that RV-14 infection stimulates S. pneumoniae
      adhesion to airway epithelial cells via increases in PAF-Rs that are partly
      mediated through activation of transcription factors. Increased adherence of S.
      pneumoniae may be one of the reasons that pneumonia develops after RV infection.

PMID- 14673775
TI  - Distinct surrogate markers for protection against Plasmodium falciparum infection
      and clinical malaria identified in a Senegalese community after radical drug
      cure.
AB  - Plasmodium falciparum expresses many antigens, which elicit various immune
      responses in exposed individuals, but no simple surrogate marker for protection
      has yet been developed. In this prospective survey, we looked for immune
      responses predictive of protection at various stages of progression from parasite
      inoculation to onset of disease. We studied 110 Senegalese volunteers from an
      area in which malaria is mesoendemic after they had received eradication therapy.
      We evaluated 4 protection-related outcomes (reappearance of parasitemia, duration
      of asymptomatic carriage, time to first clinical episode, and incidence of
      clinical episodes) in terms of levels of immunoglobulin G (IgG) against 3 crude
      parasite extracts and 5 conserved antigens during a 5-month period. Kaplan-Meier
      estimates and age-adjusted regression models showed these 4 outcomes to be
      associated with different patterns of IgG response to PfEMP3-cl5 (derived from P.
      falciparum erythrocyte membrane protein 3), PfEB200, MSP-1(19) (derived from
      merozoite surface protein-1), [NANP]10, infected red blood cell membrane, and
      merozoite and schizont extracts. It should, therefore, be possible to develop
      surrogate markers for each end point on the basis of IgG response to a limited
      number of conserved antigens.

PMID- 14673776
TI  - A novel recombinant antigen for immunodiagnosis of human cystic echinococcosis.
AB  - A pool of serum samples from mice infected with oncospheres (eggs) of
      Echinococcus granulosus was used to screen a cDNA library constructed with RNA
      extracted from protoscolex larvae from sheep hydatid cysts. One immunoreactive
      clone, designated EpC1, was shown to encode a protein of 76 residues. The
      complementary DNA (cDNA) fragment was subcloned into an expression vector, pET
      41b(+), and the resulting recombinant EpC1 glutathione S-transferase (GST) fusion
      protein (rEpC1-GST) was expressed in Escherichia coli and was affinity purified
      against the GST tag. Immunoglobulin G was the dominant antibody isotypes
      generated against rEpC1-GST. A total of 896 human serum samples were used to
      evaluate the diagnostic sensitivity and specificity of the fusion protein by
      immunoglobulin G immunoblotting; 324 serum samples from patients with cystic
      echinococcosis (CE), 172 from patients with neurocysticercosis, 89 from patients
      with alveolar echinococcosis, and 241 from patients with other infections or
      clinical presentations, as well as 70 from confirmed-negative control subjects,
      yielded an overall sensitivity of 92.2% and an overall specificity of 95.6%. The
      combined levels of sensitivity and specificity achieved with the rEpC1-GST fusion
      protein for diagnosis of CE are unprecedented, taking into account the large
      panel of serum samples that were tested.

PMID- 14673779
TI  - ProteoChip: a highly sensitive protein microarray prepared by a novel method of
      protein immobilization for application of protein-protein interaction studies.
AB  - We have developed a highly sensitive microarray protein chip, ProteoChip, coated
      with ProLinker, novel calixcrown derivatives with a bifunctional coupling
      property that permits efficient immobilization of capture proteins on solid
      matrixes and makes high-throughput analysis of protein-protein interactions
      possible. The analysis of quartz crystal microbalance showed that both monoclonal
      antibody (mAb) and antigen (Ag) bound to the gold film of the sensor surface
      coated with ProLinker B and that it is useful for studies of Ab-Ag interactions.
      ProteoChip, aminated glass slide coated with ProLinker A, was also demonstrated
      to be useful for preparation of high-density array spots by using a microarrayer
      and for analysis of analyte Ags either by direct or sandwich methods of
      fluorescence immunoassay. The detection sensitivity of ProteoChip was as low as 1
      10 femtogram/mL of analyte protein, useful for detection of tumor markers.
      ProteoChip was also useful for studies of direct protein-protein interactions as
      demonstrated by analysis of integrin-extracellular matrix protein interaction.
      These experimental results suggest that ProteoChip is a powerful tool for
      development of chip-based lead screening microarrays to monitor protein-protein
      interactions (i.e. drug target) as well as for biomarker assays which require
      high detection sensitivity.

PMID- 14673778
TI  - A fluorescent natural product for ultra sensitive detection of proteins in one
      dimensional and two-dimensional gel electrophoresis.
AB  - Lightning Fast is a sensitive fluorescence-based stain for detecting proteins in
      one-dimensional and two-dimensional polyacrylamide electrophoresis gels. It
      contains the fluorophore epicocconone from the fungus Epicoccum nigrum that
      interacts noncovalently with sodium dodecyl sulfate and protein. Stained proteins
      can be excited optimally by near-ultraviolet light of about 395 nm or with
      visible light of about 520 nm. The stain can be excited using a range of sources
      used in image analysis systems including UVA (ca. 365 nm) and UVB (ca. 302 nm)
      transilluminators; Xenon-arc lamps; 488 nm and 457 nm Argon-ion lasers; 473 nm
      and 532 nm neodymium: yttrium aluminum garnet (Nd:YAG) solid-state lasers; 543 nm
      helium-neon lasers, and emerging violet, blue and green diode lasers. Maximum
      fluorescence emission of the dye is at approximately 610 nm. The limit of
      detection in one-dimensional gels stained with Lightning Fast protein gel stain
      is less than 100 pg of protein, rivaling the current limits of matrix-assisted
      laser desorption/ionization-mass spectrometry (MALDI-MS). Lightning Fast was
      found to be considerably more sensitive than SYPRO Ruby, SYPRO Orange, silver and
      Coomassie Brilliant Blue G-250 in matched experiments. Staining takes as little
      as 3.5 h and stained proteins displayed quantitative linearity over more than
      four orders of magnitude, thereby allowing visualization of entire proteomes.
      Lightning Fast protein gel staining is compatible with subsequent peptide mass
      fingerprinting using MALDI-MS and Edman-based sequencing chemistry.

PMID- 14673780
TI  - Efficiency improvement of peptide identification for an organism without complete
      genome sequence, using expressed sequence tag database and tandem mass spectral
      data.
AB  - We compared peptide identification by database (DB) search methods with de novo
      sequencing results for proteomics study in an organism without genome sequence
      information. When the former was done by searching the Expressed Sequence Tag
      (EST) DB of the sample organism or the NCBI nonredundant (nr) protein DB of green
      plants using either the MASCOT or SEQUEST software program, it was confirmed that
      the former is as accurate as the latter. Peptides identified from EST DB were
      twice as many as those from the nr protein DB, in spite of the fact that the EST
      DB has less data (26 222 EST) than the NCBI nr protein DB (224 238). This study
      demonstrates that EST DB with tandem mass spectra can be used reliably for high
      throughput proteomics studies in an organism without genome information.

PMID- 14673781
TI  - Pattern analysis of serum proteome distinguishes renal cell carcinoma from other
      urologic diseases and healthy persons.
AB  - Despite having a relatively low incidence, renal cell carcinoma (RCC) is one of
      the most lethal urologic cancers. For successful treatment including surgery,
      early detection is essential. Currently there is no screening method such as
      biomarker assays for early diagnosis of RCC. Surface-enhanced laser
      desorption/ionization-time of flight mass spectrometry (SELDI-TOF) is a recent
      technical advance that can be used to identify biomarkers for cancers. In this
      study, we investigated whether SELDI protein profiling and artificial
      intelligence analysis of serum could distinguish RCC from healthy persons and
      other urologic diseases (nonRCC). The SELDI-TOF data was acquired from a total of
      36 serum samples with weak cation exchange-2 protein chip arrays and filtered
      using ProteinChip software. We used a decision tree algorithm c4.5 to classify
      the three groups of sera. Five proteins were identified with masses of 3900,
      4107, 4153, 5352, and 5987 Da. These biomarkers can correctly separate RCC from
      healthy and nonRCC samples.

PMID- 14673782
TI  - Proteome profiling and its use in metabolic and cellular engineering.
AB  - Proteome profiling of microorganisms makes it possible to generate valuable
      knowledge that can be used for the development of metabolic and cellular
      engineering strategies, which consequently are used to enhance the yield and
      productivity of native or foreign bioproducts and to modify cellular properties
      to improve mid-stream and down-stream processes. Advances in two-dimensional gel
      electrophoresis technology combined with mass spectrometry allow the creation of
      global scale proteome contents which can be used to elucidate valuable
      information on the dynamics of the metabolic, signaling and regulatory networks
      apart from understanding the physiological changes. In this paper, we review the
      approaches of exploiting the proteome profiling results to the development of the
      strategies for the metabolic and cellular engineering of microorganisms.

PMID- 14673783
TI  - Improvement of the two-dimensional gel electrophoresis analysis for the proteome
      study of Halobacterium salinarum.
AB  - Inherent problems exist in the use of two-dimensional gel electrophoresis (2-DE)
      for sample preparation and separation of proteins from Halobacterium salinarum.
      In particular, proteins from cells grown in 25% NaCl are difficult to resolve by
      2-DE due to the abundance of salt. To remove salts, a 3 kDa molecular weight cut
      off column was used. When soluble proteins were separated by 2-DE, most of the
      proteins were concentrated in the acidic range. For separation of proteins in the
      pH 3-6 range, ultrazoom immobilized pH gradient strips were used. In addition,
      sample separation using a IPGphor/Multiphor combined system was a more effective
      method for the proteome analysis of acidic proteins than using IPGphor for the
      isoelectric focusing step.

PMID- 14673784
TI  - Proteomic analysis of Candida magnoliae strains by two-dimensional gel
      electrophoresis and mass spectrometry.
AB  - Candida magnoliae which has been newly isolated from honey comb is an
      osmotolerant yeast to produce erythritol as a major product. Erythritol is a
      noncariogenic, low calorie sweetener and safe for diabetics. Strain development
      by chemical mutation to obtain the improved erythritol yield and productivity
      relative to the parental strain made it necessary to elucidate the physiological
      differences between the wild and mutant strains. Proteomic analyses of C.
      magnoliae wild and mutant strains with two-dimensional gel electrophoresis and
      nanoelectrospray mass spectrometry were carried out to identify intracellular
      proteins and to estimate the effects of newly characterized metabolic enzymes on
      the yeast cell growth and erythritol production. Most of the molecular mass of
      intracellular proteins were distributed in the range of pI 4-8 and molecular mass
      of approximately 130 kDa. Six out of nine protein spots expressed at different
      levels between the wild and mutant strains were analyzed with nanoelectrospray
      tandem mass spectrometry and identified by comparing amino acid sequences with
      the National Center for Biotechnology Information and Saccharomyces Genome
      Databases. Except for Ygr086cp, these proteins were believed to be the metabolic
      enzymes involved in the citric acid cycle (citrate synthase, succinyl-CoA ligase
      and fumarase) and the glycolysis pathway (pyruvate decarboxylase and enolase). Up
      regulated enzymes in the citric acid cycle could explain high growth of the C.
      magnoliae mutant strain owing to the increased NADH and ATP formation. Down
      regulated enolase and up-regulated fumarase in the mutant strain seemed to play a
      role in the improved bioconversion of erythrose-4-phosphate to erythritol
      compared with the wild strain.

PMID- 14673785
TI  - Establishment of a two-dimensional electrophoresis map for Neospora caninum
      tachyzoites by proteomics.
AB  - Expressed proteins and antigens from Neospora caninum tachyzoites were studied by
      two-dimensional gel electrophoresis and immunoblot analysis combined with matrix
      assisted laser desorption/ionization-time of flight mass spectrometry. Thirty-one
      spots corresponding to 20 different proteins were identified from N. caninum
      tachyzoites by peptide mass fingerprinting. Six proteins were identified from a
      N. caninum database (NTPase, 14-3-3 protein homologue, NcMIC1, NCDG1, NcGRA1 and
      NcGRA2), and 11 proteins were identified in closely related species using the T.
      gondii database (HSP70, HSP60, pyruvate kinase, tubulin alpha- and beta-chain,
      putative protein disulfide isomerase, enolase, actin, fructose-1,6
      bisphosphatase, lactate dehydrogenase and glyceradehyde-3-phosphate
      dehydrogenase). One hundred and two antigen spots were observed using pH 4-7 IPG
      strips on immunoblot profiles. Among them, 17 spots corresponding to 11 antigenic
      proteins were identified from a N. caninum protein map. This study involved the
      construction of in-depth protein maps for N. caninum tachyzoites, which will be
      of value for studies of its pathogenesis, drug and vaccine development, and
      phylogenetic studies.

PMID- 14673786
TI  - Proteome analysis of the responses of Panax ginseng C. A. Meyer leaves to high
      light: use of electrospray ionization quadrupole-time of flight mass spectrometry
      and expressed sequence tag data.
AB  - We performed comparative proteomic analyses in order to understand the
      physiological responses of ginseng (Panax ginseng C. A. Meyer) to high light
      (HL). As a first step, we analyzed the proteins expressed in ginseng leaves.
      Proteins extracted from leaves were separated by two-dimensional polyacrylamide
      gel electrophoresis. Protein spots were identified by tandem mass spectra
      analysis using electrospray ionization quadrupole-time of flight mass
      spectrometry (ESI Q-TOF MS). We used a ginseng expressed sequence tag (EST)
      database as well as a nonredundant protein database from NCBI to identify
      proteins. Eighty-one proteins were identified using the nr protein database, 51
      of which were also verified from the ginseng EST database. An additional 66
      proteins were identified only from the ginseng EST database. Proteins that
      function in energy metabolism, protein stabilization, and protection against
      oxidative stress were abundant. To understand the light responses of ginseng
      leaves, we studied time dependent changes in expressed proteins produced by 0-4 h
      of HL exposure. Six HL-responsive proteins were identified: three proteins were
      up-regulated (cytosolic small heat-shock protein, cytosolic ascorbate peroxidase,
      and putative major latex-like protein) and three proteins were down-regulated
      (Rieske Fe/S protein, putative 3-beta hydroxysteroid dehydrogenase/isomerase-like
      protein, and oxygen-evolving enhancer-like protein). Our results show that the
      ginseng EST database combined with ESI Q-TOF MS analysis can be used to identify
      ginseng proteins and to elucidate the protective mechanism of ginseng against HL
      induced damage.

PMID- 14673787
TI  - Proteomic analysis of differentially expressed proteins induced by rice blast
      fungus and elicitor in suspension-cultured rice cells.
AB  - We used two-dimensional electrophoresis (2-DE) and other proteomic approaches to
      identify proteins expressed in suspension-cultured rice cells in response to the
      rice blast fungus, Magnaporthe grisea. Proteins were extracted from suspension
      cultured cells at 24 and 48 h after rice blast fungus inoculation or treatment
      with elicitor or other signal molecules such as jasmonic acid (JA), salicylic
      acid, and H(2)O(2). The proteins were then polyethylene glycol fractionated
      before separation by 2-DE. Fourteen protein spots were induced or increased by
      the treatments, which we analyzed by N-terminal or internal amino acid
      sequencing. Twelve proteins from six different genes were identified. Rice
      pathogen-related protein class 10 (OsPR-10), isoflavone reductase like protein,
      beta-glucosidase, and putative receptor-like protein kinase were among those
      induced by rice blast fungus; these have not previously been reported in
      suspension-cultured rice cells. Six isoforms of probenazole-inducible protein
      (PBZ1) and two isoforms of salt-induced protein (SalT) that responded to blast
      fungus, elicitor, and JA were also resolved on a 2-DE gel and identified by
      proteome analysis. The expression level of these induced proteins both in
      suspension-cultured cells and in leaves of whole plants was analyzed by Western
      blot. PBZ1, OsPR-10, and SalT proteins from incompatible reactions were induced
      earlier and to a greater extent than those in compatible reactions. Proteome
      analysis can thus distinguish differences in the timing and amount of protein
      expression induced by pathogens and other signal molecules in incompatible and
      compatible interactions.

PMID- 14673788
TI  - Proteome analysis of hairy root from Panax ginseng C.A. Meyer using peptide
      fingerprinting, internal sequencing and expressed sequence tag data.
AB  - As an initial step to the comprehensive proteomic analysis of Panax ginseng C. A.
      Meyer, protein mixtures extracted from the cultured hairy root of Panax ginseng
      were separated by two-dimensional polyacrylamide gel electrophoresis (2-DE). The
      protein spots were analyzed and identified by peptide finger printing and
      internal amino acid sequencing by matrix-assisted laser desorption/ionization
      time of flight mass spectrometry (MALDI-TOF MS) and electrospray ionization
      quadrupole-time of flight mass spectrometry (ESI Q-TOF MS), respectively. More
      than 300 protein spots were detected on silver stained two-dimensional (2-D) gels
      using pH 3-10, 4-7, and 4.5-5.5 gradients. Major protein spots (159) were
      analyzed by peptide fingerprinting or de novo sequencing and the functions of 91
      of these proteins were identified. Protein identification was achieved using the
      expressed sequence tag (EST) database from Panax ginseng and the protein database
      of plants like Arabidopsis thaliana and Oryza sativa. However, peptide mass
      fingerprinting by MALDI-TOF MS alone was insufficient for protein identification
      because of the lack of a genome database for Panax ginseng. Only 17 of the 159
      protein spots were verified by peptide mass fingerprinting using MALDI-TOF MS
      whereas 87 out of 102 protein spots, which included 13 of the 17 proteins
      identified by MALDI-TOF MS, were identified by internal amino acid sequencing
      using tandem mass spectrometry analysis by ESI Q-TOF MS. When the internal amino
      acid sequences were used as identification markers, the identification rate
      exceeded 85.3%, suggesting that a combination of internal sequencing and EST data
      analysis was an efficient identification method for proteome analysis of plants
      having incomplete genome data like ginseng. The 2-D patterns of the main root and
      leaves of Panax ginseng differed from that of the cultured hairy root, suggesting
      that some proteins are exclusively expressed by different tissues for specific
      cellular functions. Proteome analysis will undoubtedly be helpful for
      understanding the physiology of Panax ginseng.

PMID- 14673789
TI  - Analysis of proteins expressed in rat plasma exposed to dioxin using 2
      dimensional gel electrophoresis.
AB  - Dioxins are a class of polyhalogenated aromatic hydrocarbons that induces a wide
      spectrum of toxic responses in animals. In this study, two groups of Sprague
      Dawley rats were exposed to 2,3,7,8-tetrachlorobenzo-p-dioxin (TCDD); one group
      received short-term exposure at a single dose of 1, 10, 20 or 50 microg/kg body
      weight and the other received long-term exposure to a daily low dose of 0.01,
      0.1, 1 or 2.5 microg/kg body weight for one month. Two-dimensional
      electrophoresis was utilized to resolve the protein profile of rat plasma exposed
      to TCDD at different doses. One novel and three volume-increased spots were
      identified and characterized by matrix-assisted laser desorption/ionization-time
      of flight mass spectrometry and electrospray-ionization on quadropole-TOF2 mass
      spectrometry. The novel protein was identified as plasma glutathione peroxidase
      precursor and the volume-increased proteins were cytokeratin 8 polypeptide, Ig
      lambda-1 chain C region and Ig lambda-2 chain C region. These proteins may be
      used as biomarkers to diagnose dioxin exposure and may help in understanding the
      toxic effects of dioxins.

PMID- 14673790
TI  - Monitoring protein expression by proteomics: human plasma exposed to benzene.
AB  - Low levels and long term exposure to benzene is associated with hematotoxicity
      including aplastic anemia, acute myelogenous leukemia, and lymphoma. Current
      biomonitoring methods such as urinary phenol, S-phenylmercapturic acid, and trans
      trans muconic acid were found to be unreliable as analytical methods to detect
      benzene exposure. Therefore, to search for a specific protein for biomonitoring
      benzene exposure, we investigated plasma proteins from workers (n = 50) at a
      printing company who were exposed to benzene, by two-dimensional gel
      electrophoresis. The protein profiles are significantly different (p < 0.05)
      between benzene exposed and unexposed groups, as identified by matrix-assisted
      laser desorption ionization/time of flight mass spectrometry and confirmed by
      Western blot analyses. T cell receptor beta chain (TCR beta), FK506-binding
      protein, and matrix metalloproteinase-13 were expressed only in benzene exposed
      workers. In addition, interleukin-4 receptor alpha chain and T cell surface
      glycoprotein CD1b precursor were found to be up-regulated in the plasma of
      benzene exposed workers. When we treated Jurkat cells with benzene (10 microM-10
      mM), TCR beta expression was increased in the membrane more than 6-9-fold
      compared to untreated cells. In addition, the amount of TCR beta released into
      the culture media, at benzene concentrations greater than 50 microM, increased up
      to 10 mM. Therefore, TCR beta levels in plasma could be used as a biomarker and a
      possible therapeutic target for benzene exposure.

PMID- 14673791
TI  - Differential protein expressions induced by adenovirus-mediated p16 gene transfer
      into Balb/c nude mouse.
AB  - To evaluate the safety of adenovirus-mediated gene transfer, we investigated
      differential protein expression after transducing adenoviral vector containing
      the p16(INK4a) tumor suppressor gene (Ad5CMV-p16) into Balb/c nude mice. We found
      that adenovirus-mediated p16(INK4a) gene transfer inhibited experimental lung
      metastasis, and that the intratumoral injection of Ad5CMV-p16 resulted in
      regression of A549 cell xenografted tumors in Balb/c nude mice. We investigated
      changes in protein expression after intratumoral injection of Ad5CMV-p16 or
      Ad5CMV (10(10) plaque-forming units) into A549 cell xenografted Balb/c nude mice
      by two-dimensional gel electrophoresis /matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry. Compared with the control
      (serum-free medium treated tumor cells) Ad5CMV-p16 gene transfer changed the
      expression of 29 proteins including heterogeneous nuclear ribonucleoprotein,
      protein phosphatase 2, 14-3-3 zeta protein, alpha-tubulin, and glutathione-S
      transferase P1. Moreover, both Ad5CMV-p16 and Ad5CMV up-regulated the expression
      of glutathione-S-transferase P1. In addition, Ad5CMV-p16 gene transfer did not
      seem to increase the expression of tumorigenicity-related protein in Balb/c nude
      mice. Further studies will be needed to investigate the effect of Ad5CMV-p16 on
      normal human cells and tissues for safety evaluation. These results suggest that
      the p16 gene seems to have an important role in apoptosis as well as in cell
      cycle arrest in non-small cell lung cancer.

PMID- 14673792
TI  - Characterization of a bovine pregnancy-associated protein using two-dimensional
      gel electrophoresis, N-terminal sequencing and mass spectrometry.
AB  - Bovine pregnancy-associated protein (bPAP) isolated from pregnant bovine urines
      by two-dimensional electrophoresis (2-DE) was characterized by N-terminal
      sequencing, internal sequencing, and mass spectrometric analyses using matrix
      assisted laser desorption/ionization-time of flight mass spectrometry and tandem
      mass spectrometry. Database search using the amino acid sequences and the peptide
      mass profiles showed that the protein is a novel bovine pregnancy-associated
      protein of which the N-terminus has a high similarity to collagen alpha. The
      protein has a molecular mass of 21 kDa and a pI of 6.1. The expression profiles
      of the protein from the urine of 30 pregnant and 20 nonpregnant cows
      characterized by 2-DE indicated that the expression of bPAP during pregnancy
      increased to over nmol from the pmol level basal expression of bPAP at the
      nonpregnant state with < 3% of false negatives and < 10% of false positives.
      Using the peptide sequence information, polyclonal antibodies against the bPAP
      protein were generated. The purified polyclonal antibodies against the peptide
      sequences of bPAP detected the 21 kDa protein on the blots of pregnant cow urine
      by Western blot analysis. In addition, analysis showed that the expression of
      bPAP in the urine is associated with pregnancy, but that the urine concentration
      of bPAP is not correlated with the duration of the pregnancy.

PMID- 14673793
TI  - Comparative analysis of nuclear proteins of B cells in different developmental
      stages.
AB  - The developmental stage-specific regulation of V(D)J recombination, a gene
      rearrangement process of antigen receptor gene segments, is tightly controlled in
      cells. Here we screened proteins uniquely or differentially expressed among three
      developmentally distinguishable B cells (pro-B, pre-B and mature B cells) using
      two-dimensional gel electrophoresis and mass spectrometry. Chromatin assembly
      factor 1 was uniquely expressed in pro-B cells. Purine nucleotide phosphorylase,
      LCK, E2A and many other unidentified proteins were dominantly present in the
      nucleus at the early stage of B cell development where the V(D)J recombination
      process occurs. Also, few proteins including guanidine nucleotide binding
      proteins were exclusively expressed in pre-B cell. Such findings can provide some
      information to help understand the developmental regulation of gene rearrangement
      occurring during B cell development.

PMID- 14673794
TI  - Mass spectrometry and tandem mass spectrometry analysis of rat mitochondrial ATP
      synthase: up-regulation in pancreatic acinar cells treated with cerulein.
AB  - Mitochondrion is a vulnerable intracellular target to reactive oxygen species
      (ROS). ROS have been considered to be important regulators of the pathogenesis of
      pancreatitis. This study aims to determine whether ROS induces mitochondrial
      damage by monitoring the expression level of mitochondrial ATP synthase as the
      key molecular component in mitochondria associated with cellular damage.
      Pancreatic acinar AR42J cells were treated with cerulein which induces symptoms
      similar to that associated with human acute pancreatitis. Proteins were separated
      by two-dimensional electrophoresis using pH gradients of 5-8 and identified using
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometer
      (MS), quadrupole time-of-flight MS and MS/MS with nano-electrospray. Following
      cerulein treatment, mitochondrial ATP synthase beta chain was highly expressed
      compared to nontreated cell. The protein was identified by its pI of 5.2 and
      molecular weight (56 354 Da) with 27 matched peptides. Among the MS spectrum,
      precursor ions m/z 488.28, 544.81, 631.82, 693.34, 718.38, 729.41, 801.40,
      809.39, 825.94, and 994.52 were further identified using MS/MS and confirmed the
      isolated protein to be mitochondrial ATP synthase beta chain. In conclusion,
      cerulein-induced oxidative injury may result in the induction of mitochondrial
      ATP synthase, which may act as an adaptive pathophysiological process in the
      pancreas.

PMID- 14673795
TI  - Proteome analysis of rat pancreatic acinar cells: implication for cerulein
      induced acute pancreatitis.
AB  - Cerulein pancreatitis was shown to be one of the best characterized models for
      acute pancreatitis. High doses of cerulein induce a dysregulation of the
      digestive enzyme production and cytoplasmic vacuolization and the death of acinar
      cells, edema formation, and an infiltration of inflammatory cells into the
      pancreas, which are similar symptoms shown in human acute pancreatitis. The
      present study aims to determine the differentially expressed proteins in cerulein
      treated pancreatic acinar cells as an in vitro model for acute pancreatitis.
      Pancreatic acinar AR42J cells were treated with 10(-8) M cerulein for 24 h. The
      changed protein patterns separated by two-dimensional electrophoresis using pH
      gradients of 5-8 were conclusively identified by matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry analysis of the peptide
      digests. Five differentially expressed proteins (heat shock protein 90,
      mitochondrial ATP synthase beta chain precursor, tubulin beta chain, 3
      mercaptopyruvate sulfurtransferase, mitochondrial ATP synthase subunit D) were
      identified in cerulein-treated AR42J cells. These proteins are related to
      cellular stress such as reactive oxygen species, cytoskeletal function, and cell
      signaling. In conclusion, the differentially expressed proteins will provide
      valuable information to understand the pathophysiologic mechanism of acute
      pancreatitis and may be useful for prognostic indices of acute pancreatitis.

PMID- 14673796
TI  - Proteomic and transcriptomic analysis of interleukin-1beta treated lung carcinoma
      cell line.
AB  - Mucin hypersecretion is one of the main symptoms of inflammatory disease in the
      respiratory tract. We previously reported that the pleiotypic pro-inflammatory
      cytokine, interleukin (IL)-1beta, plays a significant role in respiratory tract
      inflammation by inducing mucins. However, the molecular mechanism for mucin
      hypersecretion in the respiratory tract remains still unclear. In order to
      understand the mechanisms of mucin hypersecretion in the airway epithelium, the
      differentially expressed proteins and genes in the lung mucoepidermoid carcinoma
      cell line (NCI-H292 cells), which were treated for 6 and 24 hours with IL-1beta
      (10 ng/mL) were identified using two-dimensional polyacrylamide gel
      electrophoresis (2-D PAGE) proteomics and cDNA microarray analysis (8.6K). In the
      2-D PAGE, eight differentially expressed proteins and 14 post-translational
      modification proteins were identified at 6 and 24 hours after the IL-1beta
      treatment. Four hundred and thirteen genes (6.6%) and 115 genes (2.0%) were
      differentially expressed, respectively, at 6 and 24 hours after the IL-1beta
      treatment by microarray analysis. The differentially expressed genes and proteins
      that were regulated by the IL-1beta-treatment were mostly in the metabolic
      pathway rather than in the regulatory pathway. These results clearly show that
      the transcript levels have little value in predicting the extent of protein
      expression.

PMID- 14673797
TI  - Strategic shotgun proteomics approach for efficient construction of an expression
      map of targeted protein families in hepatoma cell lines.
AB  - An expression map of the most abundant proteins in human hepatoma HepG2 cells was
      established by a combination of complementary shotgun proteomics approaches. Two
      dimensional liquid chromatography (LC)-nano electrospray ionization (ESI) tandem
      mass spectrometry (MS/MS) as well as one-dimensional LC-matrix-assisted laser
      desorption/ionization MS/MS were evaluated and shown that additional separation
      introduced at the peptide level was not as efficient as simple prefractionation
      of protein extracts in extending the range and total number of proteins
      identified. Direct LC-nanoESI MS/MS analyses of peptides from total solubilized
      fraction and the excised gel bands from one-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis fractionated insolubilized fraction afforded
      the best combination in efficient construction of a nonredundant cell map.
      Compiling data from multiple variations of rapid shotgun proteomics analyses is
      nonetheless useful to increase sequence coverage and confidence of hits
      especially for those proteins identified primarily by a single or two peptide
      matches. While the returned hit score in general reflects the abundance of the
      respective proteins, it is not a reliable index for differential expression.
      Using another closely related hepatoma Hep3B as a comparative basis, 16 proteins
      with more than two-fold difference in expression level as defined by spot
      intensity in two-dimensional gel electrophoresis analysis were identified which
      notably include members of the heat shock protein (Hsp) and heterogeneous nuclear
      ribonucleoprotein (hnRPN) families. The observed higher expression level of hnRNP
      A2/B1 and Hsp90 in Hep3B led to a search for reported functional roles mediated
      in concert by both these multifunctional cellular chaperones. In agreement with
      the proposed model for telomerase and telomere bound proteins in promoting their
      interactions, data was obtained which demonstrated that the expression proteomics
      data could be correlated with longer telomeric length in tumorigenic Hep3B. This
      biological significance constitutes the basis for further delineation of the
      dynamic interactions and modifications of the two protein families and
      demonstrated how proteomic and biological investigation could be mutually
      substantiated in a productive cycle of hypothesis and pattern driven research.

PMID- 14673798
TI  - Proteomic profiling of heat shock protein 70 family members as biomarkers for
      hepatitis C virus-related hepatocellular carcinoma.
AB  - To identify proteins linked to the pathogenesis of hepatocellular carcinoma (HCC)
      associated with hepatitis C virus (HCV), we profiled protein expression levels in
      samples of HCC. To identify essential proteins, ten samples of HCV-related HCC
      were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry. These experiments
      revealed increased levels of nine proteins in cancerous tissues compared to
      levels in corresponding noncancerous liver tissues. We focused on four members of
      the heat shock protein 70 family: 78 kDa glucose-regulated protein (GRP78), heat
      shock cognate 71 kDa protein (HSC70), 75 kDa glucose-regulated protein (GRP75),
      and heat shock 70 kDa protein 1 (HSP70.1). These results were confirmed by
      immunoblot analysis. In an additional 11 samples, the same expression patterns of
      these four proteins were observed. In total, 21 samples showed statistically
      significant up-regulation of GRP78, GRP75 and HSP70.1 in cancerous tissues. HSC70
      showed a tendency toward overexpression. There has been no report describing
      overexpression of these four proteins simultaneously in HBV-related HCC as well
      as nonviral HCC. Our results suggest that these four proteins play important
      roles in the pathogenesis of HCV-related HCC and could be molecular targets for
      diagnosis and treatment of this disease.

PMID- 14673801
TI  - A new horizon of proteomics in Korea.

PMID- 14673803
TI  - Neural correlates of segmental and tonal information in speech perception.
AB  - The Chinese language provides an optimal window for investigating both segmental
      and suprasegmental units. The aim of this cross-linguistic fMRI study is to
      elucidate neural mechanisms involved in extraction of Chinese consonants, rhymes,
      and tones from syllable pairs that are distinguished by only one phonetic feature
      (minimal) vs. those that are distinguished by two or more phonetic features (non
      minimal). Triplets of Chinese monosyllables were constructed for three tasks
      comparing consonants, rhymes, and tones. Each triplet consisted of two target
      syllables with an intervening distracter. Ten Chinese and English subjects were
      asked to selectively attend to targeted sub-syllabic components and make same
      different judgments. Direct between-group comparisons in both minimal and non
      minimal pairs reveal increased activation for the Chinese group in predominantly
      left-sided frontal, parietal, and temporal regions. Within-group comparisons of
      non-minimal and minimal pairs show that frontal and parietal activity varies for
      each sub-syllabic component. In the frontal lobe, the Chinese group shows
      bilateral activation of the anterior middle frontal gyrus (MFG) for rhymes and
      tones only. Within-group comparisons of consonants, rhymes, and tones show that
      rhymes induce greater activation in the left posterior MFG for the Chinese group
      when compared to consonants and tones in non-minimal pairs. These findings
      collectively support the notion of a widely distributed cortical network
      underlying different aspects of phonological processing. This neural network is
      sensitive to the phonological structure of a listener's native language. Hum.
      Brain Mapping 20:185-200, 2003.

PMID- 14673804
TI  - Cluster analysis of fMRI data using dendrogram sharpening.
AB  - The major disadvantage of hierarchical clustering in fMRI data analysis is that
      an appropriate clustering threshold needs to be specified. Upon grouping data
      into a hierarchical tree, clusters are identified either by specifying their
      number or by choosing an appropriate inconsistency coefficient. Since the number
      of clusters present in the data is not known beforehand, even a slight variation
      of the inconsistency coefficient can significantly affect the results. To address
      these limitations, the dendrogram sharpening method, combined with a hierarchical
      clustering algorithm, is used in this work to identify modality regions, which
      are, in essence, areas of activation in the human brain during an fMRI
      experiment. The objective of the algorithm is to remove data from the low-density
      regions in order to obtain a clearer representation of the data structure. Once
      cluster cores are identified, the classification algorithm is run on voxels, set
      aside during sharpening, attempting to reassign them to the detected groups. When
      applied to a paced motor paradigm, task-related activations in the motor cortex
      are detected. In order to evaluate the performance of the algorithm, the obtained
      clusters are compared to standard activation maps where the expected hemodynamic
      response function is specified as a regressor. The obtained patterns of both
      methods have a high concordance (correlation coefficient = 0.91). Furthermore,
      the dependence of the clustering results on the sharpening parameters is
      investigated and recommendations on the appropriate choice of these variables are
      offered. Hum. Brain Mapping 20:201-219, 2003.

PMID- 14673805
TI  - Detecting low-frequency functional connectivity in fMRI using a self-organizing
      map (SOM) algorithm.
AB  - Low-frequency oscillations (<0.08 Hz) have been detected in functional MRI
      studies, and appear to be synchronized between functionally related areas. A
      current challenge is to detect these patterns without using an external
      reference. Self-organizing maps (SOMs) offer a way to automatically group data
      without requiring a user-biased reference function or region of interest. Resting
      state functional MRI data was classified using a self-organizing map (SOM).
      Functional connectivity between the left and right motor cortices was detected in
      five subjects, and was comparable to results from a reference-based approach.
      SOMs are shown to be an attractive option in detecting functional connectivity
      using a model-free approach. Hum. Brain Mapping 20:220-226, 2003.

PMID- 14673806
TI  - Model assessment and model building in fMRI.
AB  - Model quality is rarely assessed in fMRI data analyses and less often reported.
      This may have contributed to several shortcomings in the current fMRI data
      analyses, including: (1) Model mis-specification, leading to incorrect inference
      about the activation-maps, SPM[t] and SPM[F]; (2) Improper model selection based
      on the number of activated voxels, rather than on model quality; (3) Under
      utilization of systematic model building, resulting in the common but suboptimal
      practice of using only a single, pre-specified, usually over-simplified model;
      (4) Spatially homogenous modeling, neglecting the spatial heterogeneity of fMRI
      signal fluctuations; and (5) Lack of standards for formal model comparison,
      contributing to the high variability of fMRI results across studies and centers.
      To overcome these shortcomings, it is essential to assess and report the quality
      of the models used in the analysis. In this study, we applied images of the
      Durbin-Watson statistic (DW-map) and the coefficient of multiple determination
      (R(2)-map) as complementary tools to assess the validity as well as goodness of
      fit, i.e., quality, of models in fMRI data analysis. Higher quality models were
      built upon reduced models using classic model building. While inclusion of an
      appropriate variable in the model improved the quality of the model, inclusion of
      an inappropriate variable, i.e., model mis-specification, adversely affected it.
      Higher quality models, however, occasionally decreased the number of activated
      voxels, whereas lower quality or inappropriate models occasionally increased the
      number of activated voxels, indicating that the conventional approach to fMRI
      data analysis may yield sub-optimal or incorrect results. We propose that model
      quality maps become part of a broader package of maps for quality assessment in
      fMRI, facilitating validation, optimization, and standardization of fMRI result
      across studies and centers. Hum. Brain Mapping 20:227-238, 2003.

PMID- 14673807
TI  - Fetal brain activity in response to a visual stimulus.
AB  - Previous studies have demonstrated the use of functional magnetic resonance
      imaging (fMRI) to assess fetal brain activity. To extend these studies, a fetal
      fMRI experiment using a visual stimulus has been performed at 0.5 T. This used a
      block fMRI paradigm with a bright, constant-intensity light source being shone at
      the maternal abdomen for 8 sec followed by 16 sec of darkness. This was repeated
      typically 40 times on nine subjects all of whom were greater than 36 weeks
      gestational age. Of these, one could not be analysed due to motion, three did not
      show significant activation, and five showed significant activation (P < 0.0085).
      In all cases, activation was localised within the frontal cortex. Exact
      localisation was difficult but this may correspond to the frontal eye fields and
      dorsolateral prefontal cortex. In no cases was significant activation present
      within the occipital region as would have been expected and was observed in 2/8
      adult subjects. Hum. Brain Mapping 20:239-245, 2003.

PMID- 14673808
TI  - Early stage Parkinson's disease patients and normal volunteers: comparative
      mechanisms of sequence learning.
AB  - Early-stage nondemented Parkinson's disease (PD(es)) patients can learn short but
      not long sequences as well as controls. We have previously shown that to achieve
      normal performance, PD(es) patients activated the same right-sided cortical
      regions as controls plus the homologous left sided cortex and bilateral
      cerebellum. In this study, we evaluated two related hypotheses to explain the
      behavioral abnormalities and the increased bilateral brain activation observed in
      the PD(es) group. Hypothesis 1 proposed that PD(es) patients recruit regions from
      a normal bilateral network specialized for sequence learning that healthy
      controls would activate if performing difficult tasks. Thus, PD(es) patients can
      learn short sequences as well as controls. Hypothesis 2 proposed that information
      processing within the network in the PD(es) group is impaired. Thus, PD(es)
      patients cannot learn as difficult a sequence as controls. To test hypothesis 1,
      we increased task difficulty and statistical power in the control group and
      showed that the control and the PD(es) groups activated the same regions. To test
      hypothesis 2, we analyzed the equal performance data using two partial least
      squares (PLS) multivariate analyses. The task-PLS analysis showed that to perform
      equally with controls, the PD(es) group expressed the normal bilateral network
      more than the control group. The behavior-PLS analysis showed that the
      correlation between learning performance and regional activation was
      significantly different between the groups. We conclude that PD(es) patients have
      near normal learning if task difficulty is moderate because they can recruit
      additional regions from a normal bilateral network specialized for sequence
      learning. However, when a difficult task would normally require bilateral
      activation, PD(es) patients fail to learn because information processing within
      the network is impaired. Hum. Brain Mapp. 20:246-258, 2003.

PMID- 14673809
TI  - Modelling supply and demand influences on the use of health care: implications
      for deriving a needs-based capitation formula.
AB  - Many health-care systems allocate funding according to measures of need. The
      utilisation approach for measuring need rests on the assumptions that use of
      health care is determined by demand and supply and that need is an important
      element of demand. By estimating utilisation models which allow for supply it is
      possible to isolate the socio-economic and health characteristics which affect
      demand. A subset of these variables can then be identified by a combination of
      judgement and further analysis as needs variables to inform funding allocations.
      We estimate utilisation models using newly assembled data on admissions to acute
      hospitals, measures of supply, morbidity and socio-economic characteristics for
      8414 small geographical areas in England. We make a number of methodological
      innovations including deriving additional measures of specific morbidities at
      small area level from individual level survey data. We compare models with
      different specifications for the effect of waiting times and provider
      characteristics, with total, planned and unplanned hospital admissions, and
      estimated at small area (ward) and primary care organisation (general practice)
      level. After allowing for waiting times, distance, capacity and the availability
      of private health care, measures of mortality, self-reported morbidity, low
      education and low income increase the use of health care. We find evidence of
      horizontal inequity with respect to ethnicity and employment and suggest a method
      for reducing its effects when deriving a needs-based allocation formula.

PMID- 14673810
TI  - Classical versus relational approaches to understanding controls on a contract
      with independent GPs in South Africa.
AB  - Contracts have played a central role in public sector reforms in developed
      countries over the last decade, and research increasingly highlights their varied
      nature. In low and middle income countries the use of contracts is encouraged but
      little attention has been paid to features of the setting that may influence
      their operation. A qualitative case study was used to examine different
      dimensions of a contract with private GPs in South Africa. Features of the
      contract are compared with the notions of classical and relational contracts.
      Formal aspects of the contract such as design, monitoring and resort to sanctions
      were found to offer little control over its outcome. The relational rather than
      classical model of contracting offered a more meaningful framework of analysis,
      with social and institutional factors found to play an important role. In
      particular, the individual nature of GP practices highlighted the role played by
      individual motivation where a contract exercised little formal control. Due to
      the similarity of factors likely to be present, results are argued to be relevant
      in many other LMIC settings, and policy-makers considering contracts for clinical
      services are advised to consider the possibility of experiencing a similar
      outcome.

PMID- 14673811
TI  - Analysis of hospital length of stay and discharge destination using hazard
      functions with unmeasured heterogeneity.
AB  - The hospital length-of-stay and the discharge destination of a Medicare patient
      are the outcomes of one decision process involving the interests of the patient,
      the hospital, and the firms offering covered post-hospital care. We use a
      competing risk hazard estimation procedure and adjust for unobserved
      heterogeneity with a non-parametric technique to identify significant factors in
      the decision process. A patient's health and socio-economic characteristics, the
      availability of informal care, local market area conditions, and Medicare
      policies influence length-of-stay and discharge destination. The substitution we
      find between hospital and post-hospital care and among post-hospital care
      alternatives has policy implications for Medicare.

PMID- 14673812
TI  - An experiment on simplifying conjoint analysis designs for measuring preferences.
AB  - In conjoint analysis (CA) studies, choosing between scenarios with multiple
      health attributes may be demanding for respondents. This study examined whether
      simplifying the choice task in CA designs, by using a design with more overlap of
      attribute levels, provides advantages over standard minimal-overlap methods. Two
      experimental conditions, minimal and increased-overlap discrete choice CA
      designs, were administered to 353 respondents as part of a larger HIV testing
      preference survey. In the minimal-overlap survey, all six attribute levels were
      allowed to vary. In the increased-overlap survey, an average of two attribute
      levels were the same between each set of scenarios. We hypothesized that the
      increased-overlap design would reduce cognitive burden, while minimally impacting
      statistical efficiency. We did not find any significant improvement in
      consistency, willingness to trade, perceived difficulty, fatigue, or efficiency,
      although several results were in the expected direction. However, evidence
      suggested that there were differences in stated preferences. The results increase
      our understanding of how respondents answer CA questions and how to improve
      future surveys.

PMID- 14673813
TI  - Willingness to pay for a QALY.
AB  - A willingness to pay (WTP) per quality-adjusted-life year (QALY) of DKK 88,000
      was estimated on the basis of elicited preferences for health states. The WTP per
      QALY estimate presented here differs considerably from that implied in contingent
      valuation studies, suggesting that WTP for reducing risk of death is based on
      other preference structures than is ex post WTP for improvements in quality of
      life. Results further suggest that different preference structures may exist when
      respondents are faced with WTP questions in which case elimination of minor
      health problems are associated with negligible utility.

PMID- 14673814
TI  - An empirical comparison of EQ-5D and SF-6D in liver transplant patients.
AB  - There remains disagreement about the preferred utility-based measure of health
      related quality of life for use in constructing quality-adjusted life years
      (QALYs). The recent development of a new measure, the SF-6D, has highlighted this
      issue. The SF-6D and EuroQol EQ-5D measure health-related utilities on a scale
      where 0 represents death and 1 represents full health, and both have utility
      scores generated from random samples of the general UK population. This study
      explored whether, in a large sample of liver transplant patients, the two
      instruments provide similar results. The empirical data highlight important
      variation in the results generated from the use of the two instruments. The data
      are consistent with a view that the SF-6D does not describe health states at the
      lower end of the utility scale but is more sensitive than EQ-5D in detecting
      small changes towards the top of the scale.

PMID- 14673815
TI  - De novo sequencing of novel neuropeptides directly from Ascaris suum tissue using
      matrix-assisted laser desorption/ionization time-of-flight/time-of-flight.
AB  - Direct analysis of tissue by matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) allows for the rapid profiling of biological molecules
      with minimal loss of sample or degradation and reduced likelihood of chemical
      modification. However, there are still considerable challenges to overcome due to
      the complexity of tissue and the low quantity of endogenous peptide in a single
      cell. These problems are exacerbated in the nematode Ascaris suum because of the
      small size of individual neurons and the paucity of peptide per cell. In an
      effort to address these difficulties, the recently developed matrix-assisted
      laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF)
      technology was used in combination with an on-target derivatization in order to
      sequence novel neuropeptides directly from Ascaris nervous tissue. Direct MALDI
      TOF/TOF analysis of Ascaris tissue provided the complete amino acid sequences for
      a previously characterized neuropeptide as well as for three novel peptides with
      homologues found in other nematodes. These results demonstrate a method for the
      rapid characterization of sub-femtomolar amounts of peptide directly from tissue
      using MALDI-TOF/TOF.

PMID- 14673816
TI  - Enzymatic strategies for the characterization of nucleic acids by electrospray
      ionization mass spectrometry.
AB  - Electrospray ionization mass spectrometry (ESI-MS) is a powerful technique used
      for the identification and characterization of DNA polymorphisms. Continual
      improvement in instrument design assures high mass measurement accuracy,
      sensitivity, and resolving power. This work describes an eclectic array of
      enzymatic strategies we have invoked in order to detect single-nucleotide
      polymorphisms by ESI-MS, although other applications may be envisioned. One
      strategy combines the use of two enzymes, exonuclease III and lambda exonuclease,
      to provide a ladder of single-stranded DNA fragments for straightforward sequence
      identification by mass spectrometry. A second strategy combines restriction
      enzymes to screen for polymorphisms present within specific amplicons. Finally,
      we describe the use of stable-isotope-labeled nucleotides for the determination
      of length and base composition of a PCR product.

PMID- 14673817
TI  - Determination of atrazine, deethylatrazine and simazine in water at parts-per
      trillion levels using solid-phase extraction and gas chromatography/ion trap mass
      spectrometry.
AB  - Methods for trace analysis of atrazine and simazine in water have been developed
      by using stable-isotope dilution with detection by gas chromatography/mass
      spectrometry. D(5)-Atrazine was used as the internal standard for the
      determination of atrazine and deethylatrazine, while (13)C(3)-simazine was used
      for simazine analysis. Water samples were fortified with known amounts of the
      internal standards and submitted to solid-phase extraction with a C(18) bonded
      silica cartridge. A gas chromatograph coupled with an ion-trap mass spectrometer
      was used to analyze the water sample extracts. Method detection limits were 38
      parts-per-trillion (ppt) for atrazine and deethylatrazine and 75 ppt for
      simazine. The accuracy of the method, represented by relative analytical errors,
      was less than 15%, and the method precision was less than 5% (relative standard
      deviation, n = 9). The method was successfully applied to analyze surface water
      samples collected from a reservoir and a river at ppt levels.

PMID- 14673818
TI  - Application of the StrOligo algorithm for the automated structure assignment of
      complex N-linked glycans from glycoproteins using tandem mass spectrometry.
AB  - Oligosaccharides associated with proteins are known to give these molecules
      specific conformations and functions. Analysis of proteins would not be complete
      without studying the glycans. However, high-throughput techniques in proteomics
      will soon overwhelm the current capacity of methods if no automation is
      incorporated into glycomics. New capabilities of the StrOligo algorithm
      introduced for this purpose (Ethier et al., Rapid Commun. Mass Spectrom., 2002;
      16: 1743) will be discussed here. Experimental tandem mass spectra were acquired
      to test the algorithm using a hybrid quadrupole-time-of-flight (QqTOF) instrument
      with a matrix-assisted laser desorption/ionization (MALDI) source. The samples
      were N-linked oligosaccharides from monoclonal antibody IgG, beta interferon and
      fetuin, detached by enzymatic deglycosylation and labeled at the reducing end.
      Improvements to the program were made in order to reduce the need for user
      intervention. StrOligo strips the spectra down to monoisotopic peaks only. The
      algorithm first builds a relationship tree, accounting for each observed loss of
      a monosaccharide moiety, and then analyzes the tree and proposes possible
      structures from combinations of adducts and fragment ion types. A score, which
      reflects agreement with experimental results, is then given to each proposed
      structure. The program then decides which combination is the best one and labels
      relevant peaks in the experimental mass spectrum using a modified nomenclature.
      The usefulness of the algorithm has been demonstrated by assigning structures to
      several glycans released from glycoproteins. The analysis was completed in less
      than 2 minutes for any glycan, which is a substantial improvement over manual
      interpretation.

PMID- 14673819
TI  - Dynamic calibration and dissolved gas analysis using membrane inlet mass
      spectrometry for the quantification of cell respiration.
AB  - A membrane inlet mass spectrometer connected to a miniaturized reactor was
      applied for dynamic dissolved gas analysis. Cell samples were taken from 7 mL
      shake flask cultures of Corynebacterium glutamicum ATCC 13032, and transferred to
      the 12 mL miniaturized reactor. There, oxygen uptake and carbon dioxide and its
      mass isotopomer production rates were determined using a new experimental
      procedure and applying nonlinear model equations. A novel dynamic method for the
      calibration of the membrane inlet mass spectrometer using first-order dynamics
      was developed. To derive total dissolved concentration of all carbon dioxide
      species (C(T)) from dissolved carbon dioxide concentration ([CO(2)](aq)), the
      ratio of C(T) to [CO(2)](aq) was determined by nonlinear parameter estimation,
      whereas the mass transfer coefficient of CO(2) was determined by the Wilke-Chang
      correlation. Subsequently, the suitability of the model equations for respiration
      measurements was examined using residual analysis and the Jarque-Bera hypothesis
      test. The resulting residuals were found to be random with normal distribution,
      which proved the adequacy of the application of the model for cell respiration
      analysis. Hence, dynamic changes in respiration activities could be accurately
      analyzed using membrane inlet mass spectrometry with the novel calibration
      method.

PMID- 14673820
TI  - A strategy for metabolite identification using triple-quadrupole mass
      spectrometry with enhanced resolution and accurate mass capability.
AB  - Using a single platform of a triple-quadrupole mass spectrometer equipped with
      enhanced resolution and accurate mass capabilities, a strategy for metabolite
      identification of a drug in a biological matrix has been demonstrated. The
      strategy is based on first screening for metabolites via neutral loss and
      precursor ion scan schemes, devised as the result of the product ion spectrum of
      a matrix-free standard of the drug. The accurate masses of the precursor ions
      identified via the two scan schemes plus the precursor ions of structurally
      likely metabolites are then determined by enhanced resolution, accurate mass (AM)
      selected ion monitoring (SIM). The identities of the metabolites are further
      established by determining the accurate masses of the product ions via enhanced
      resolution AM selected reaction monitoring (SRM). The feasibility of the strategy
      was demonstrated using a liver microsome incubation sample of nefazodone, an
      antidepressant drug. The neutral loss and precursor ion screening runs were able
      to identify most of the metabolites of nefazodone. The subsequent SIM and SRM
      experiments gave mass accuracy of better than +/-0.003 u for the masses of the
      precursor and product ions of nefazodone and all the metabolites. The ability to
      perform metabolite screening by using the scan features followed by accurate mass
      determinations on the same instrument is an attractive feature of using a triple
      quadrupole mass spectrometer with enhanced resolution and accurate mass
      capability.

PMID- 14673821
TI  - Detection of immune complexes by matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was used
      to detect an immune complex formed between beta-lactoglobulin and polyclonal anti
      beta-lactoglobulin antibody in the gas phase. The most important experimental
      parameters to detect such a specific antibody-antigen complex by MALDI were the
      use of solutions at near-neutral pH and of sinapinic acid matrix prepared by the
      dried-droplet method. Under such conditions, predominantly one but also two
      molecules of antigen protein were complexed by the antibody. Specific formation
      of the antibody-antigen complex was confirmed by performing competitive
      reactions. Addition of antibody to a 1:1 mixture of beta-lactoglobulin and one
      control protein resulted not only in the appearance of the expected antibody
      antigen complex, but also in a strong decrease in the free beta-lactoglobulin
      signal, while the abundance of the control protein was not influenced.

PMID- 14673822
TI  - Mass spectrometric studies of cisplatin-induced changes of hemoglobin.
AB  - This study reports on structural changes of hemoglobin (Hb) that were induced by
      cisplatin binding. Two techniques, nanoelectrospray quadrupole time-of-flight
      mass spectrometry (nanoES-MS) and high-performance liquid chromatography with
      inductively coupled plasma mass spectrometry (HPLC/ICPMS), were developed to
      facilitate this study. Nanospray MS analyses of cisplatin and Hb reaction
      mixtures demonstrated that the ion at m/z 616.5, the heme group, increased with
      an increase of cisplatin concentration, indicating the loss of heme groups from
      the intact protein. This conclusion was also supported by the increase of
      cisplatin-alpha or -beta complex formation. The change of the Hb-bound Fe was
      further investigated by monitoring Fe signals using size-exclusion HPLC/ICPMS.
      After incubation with cisplatin at clinically relevant concentrations, under
      physiological conditions, the amount of Fe bound to Hb was reduced while
      formation of cisplatin-Hb complexes increased. Flow-injection ICPMS analysis of
      the Fe contents in the low molecular weight fraction (<3000 Da) of the reaction
      mixtures after size fractionation further demonstrated a corresponding increase
      of Fe with the increase of cisplatin concentrations. HPLC/ICPMS detected three Hb
      cisplatin complexes, one of which eluted at the same retention time as Hb while
      the other two complexes eluted later than Hb. With clinically relevant
      concentrations of cisplatin (0.05-1.0 microM) and 10 microM of Hb, the
      concentrations of the Hb-cisplatin complexes were determined in the range 0.1-64
      nM. These results, obtained from nanoES-MS, HPLC/ICPMS, and FIA-ICPMS,
      demonstrate that cisplatin binding to Hb resulted in the dissociation of the heme
      group from the intact protein.

PMID- 14673823
TI  - Automated discrimination of polymerase chain reaction products with closely
      related sequences by software-based detection of characteristic peaks in product
      ion spectra.
AB  - A computer-based method is described for automated detection of peaks in product
      ion spectra that allows discrimination of structurally related polymerase chain
      reaction (PCR) products. PCR products of K-ras mutants having single nucleotide
      substitutions and isomeric sequence changes in positions 1 and 2 of codon 12
      (e.g. TGT and GTT) were used as a model system. SpecDiff, a tool for
      differentiating pairs of mass spectra by identifying peaks that either differ in
      relative intensity between spectra or only appear in one of a pair of spectra,
      was created to help automate detection. This program was demonstrated to have
      great utility in detection of mutations and could also be useful as a general
      tool for differentiating other molecules of closely related structure.

PMID- 14673824
TI  - Fourier transform ion cyclotron resonance mass spectrometry using atmospheric
      pressure photoionization for high-resolution analyses of corticosteroids.
AB  - Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) was coupled
      with atmospheric pressure photoionization (APPI) for the first time and used for
      the analysis of several corticosteroids.1 The analytes showed excellent response
      using APPI when compared with both electrospray ionization (ESI) and atmospheric
      pressure chemical ionization (APCI). APPI has the advantage of requiring less
      heat for desolvation, resulting in less thermal degradation of the analytes and
      higher signal-to-noise than APCI. In terms of ultimate sensitivity, APPI is more
      efficient than either ESI or APCI for the analysis of corticosteroids. With some
      compounds, the high-resolution capability of FTICRMS was necessary to obtain an
      accurate mass due to contributions of the M(+.) (13)C isotope in the [M+H](+) ion
      peak.

PMID- 14673825
TI  - Kinetics of gas-phase hydrogen/deuterium exchange and gas-phase structure of
      protonated phenylalanine, proline, tyrosine and tryptophan.
AB  - Site-specific rate constants for the gas-phase hydrogen/deuterium (H/D) exchange
      of four, three, five and five hydrogen atoms in protonated phenylalanine (Phe),
      proline (Pro), tyrosine (Tyr) and tryptophan (Trp), respectively, were determined
      from matrix-assisted laser desorption/ionization Fourier transform ion cyclotron
      resonance mass spectrometry (MALDI-FTICRMS) experiments with D(2)O, D(2)S, and
      CH(3)OD as deuterating agents. No H/D exchange was observed with D(2)S. For
      exchange with both CD(3)OD and D(2)O, which is about ten times slower in the
      latter, results indicate for all compounds protonation of the alpha-amino group
      in agreement with theoretical results. Also, with both reagents, all compounds
      exchange at the COOH site more than ten times faster than at the protonation
      site, with OH and NH sites of Tyr and Trp, respectively, exchanging slowest. The
      observation of H/D exchange despite the high differences in proton affinities
      between the amino acids and deuterating agent exceeding 200 kJ mol(-1) is in
      agreement with lowering of the barrier for proton transfer through hydrogen
      bonding proposed by Lebrilla and coworkers.

PMID- 14673826
TI  - Acid-induced denaturation of cellular retinol-binding proteins types I and II
      studied by electrospray mass spectrometry.
AB  - The acid-induced denaturation of cellular retinol-binding proteins types I and II
      (CRBP I and II), in the presence and in the absence of the ligand, was studied by
      electrospray ionization mass spectrometry (ESI-MS) in the pH range 6.9-2.4. To
      avoid artifacts generated by the ESI process, suitable interface parameters were
      selected. Different charge-state distributions were observed in the ESI-MS
      spectra, reflecting the pH-dependent equilibria among protein conformations in
      solution. In the absence of retinol, CRBP II appeared to be more resistant than
      CRBP I to acid denaturation. The bound ligand stabilized both carriers, with a
      markedly higher effect on CRBP I. Retinol release from the ligand-bound carriers
      and protein denaturation occurred concomitantly. This finding suggests that the
      lowering of pH, reported to occur in proximity to a biomembrane, might contribute
      to the conformational transitions required to promote dissociation of the
      otherwise very stable retinal-carrier complexes and thus permit targeted delivery
      of vitamin A to the enzymes involved in its metabolism.

PMID- 14673827
TI  - Electrospray mass spectrometry in the differentiation of some isomeric
      trimethylfurocoumarins.
AB  - Electrospray mass spectrometry (ES-MS) was successfully employed for the
      structural differentiation of six isomeric trimethylfurocoumarins of possible
      pharmaceutical interest. Two different approaches were employed. The first was
      based on MS(n) experiments of MH(+) ions. Although the product ion spectra of
      MH(+) of the isomers are very similar, the MS(3) spectra of the collisionally
      generated [MH[bond]CO](+) ions show some characteristic differences. The second
      approach was based on complexation of the molecules with Li(+), Na(+) and K(+)
      using ESI-MS of sample solutions containing alkali ions in a 100:1 molar ratio
      with respect to the analyte. Significant differences were observed in complex
      production yields, and these were related to the dimension of the alkali ion and
      to the steric availability of chelating groups in the different isomers.

PMID- 14673828
TI  - Characteristic fragmentation of bacteriohopanepolyols during atmospheric pressure
      chemical ionisation liquid chromatography/ion trap mass spectrometry.
AB  - Bacteriohopanepolyols (BHPs) fragment via characteristic pathways during
      atmospheric pressure chemical ionisation liquid chromatography/ion trap mass
      spectrometry (APCI-LC/MS(n)). Comparison of the MS(2) spectra of bacteriohopane
      32,33,34,35-tetrol (BHT) and 2 beta-methylbacteriohopane-32,33,34,35-tetrol has
      confirmed the previously proposed ring-C cleavage occurring between C-9 and 11
      and C-8 and 14. This fragmentation, diagnostic of all hopanoids, also occurs in
      BHPs containing an amino group (-NH(2)) at C-35 although the higher relative
      stability of the ion limits this fragmentation to a minor process after
      protonation of the basic nitrogen function. Studies of a number of cell cultures
      including a prochlorophyte (Prochlorothrix hollandica) and a cyanobacterium
      (Chlorogloeopsis LA) demonstrate the power of this technique to detect composite
      BHPs with a complex biological functionality at C-35. We also report the first
      observation of intact pentafunctionalised bacteriohopanepolyols using this
      method.

PMID- 14673829
TI  - Development of a liquid chromatographic time-of-flight mass spectrometric method
      for the determination of unlabelled and deuterium-labelled alpha-tocopherol in
      blood components.
AB  - A method is described for the analysis of deuterated and undeuterated alpha
      tocopherol in blood components using liquid chromatography coupled to an
      orthogonal acceleration time-of-flight (TOF) mass spectrometer. Optimal
      ionisation conditions for undeuterated (d0) and tri- and hexadeuterated (d3 or
      d6) alpha-tocopherol standards were found with negative ion mode electrospray
      ionisation. Each species produced an isotopically resolved single ion of exact
      mass. Calibration curves of pure standards were linear in the range tested (0-1.5
      microM, 0-15 pmol injected). For quantification of d0 and d6 in blood components
      following a standard solvent extraction, a stable-isotope-labelled internal
      standard (d3-alpha-tocopherol) was employed. To counter matrix ion suppression
      effects, standard response curves were generated following identical solvent
      extraction procedures to those of the samples. Within-day and between-day
      precision were determined for quantification of d0- and d6-labelled alpha
      tocopherol in each blood component and both averaged 3-10%. Accuracy was assessed
      by comparison with a standard high-performance liquid chromatography (HPLC)
      method, achieving good correlation (r(2) = 0.94), and by spiking with known
      concentrations of alpha-tocopherol (98% accuracy). Limits of detection and
      quantification were determined to be 5 and 50 fmol injected, respectively. The
      assay was used to measure the appearance and disappearance of deuterium-labelled
      alpha-tocopherol in human blood components following deuterium-labelled (d6) RRR
      alpha-tocopheryl acetate ingestion. The new LC/TOFMS method was found to be
      sensitive, required small sample volumes, was reproducible and robust, and was
      capable of high throughput when large numbers of samples were generated.

PMID- 14673830
TI  - A comparison of accurate mass techniques for the structural elucidation of
      fluconazole.
AB  - Mass spectrometry plays a major role in the structural elucidation and
      characterisation of drug candidates and related substances. Accurate mass data
      allow the mathematical prediction of molecular formula of both precursor and
      fragment ions. In this paper, a comparison of the accurate mass data obtained for
      the fragmentation of fluconazole, an antifungal drug, by three different methods
      is made: electron ionisation (EI) using a magnetic sector instrument;
      electrospray ionisation (ES) using a Fourier transform ion cyclotron mass
      spectrometer (FTICRMS); and ES using a quadrupole-time-of-flight mass
      spectrometer (Q-ToF). It is clear from the data obtained that mass accuracy is
      not simply a function of instrument resolution. The subtle differences observed
      between collisionally activated dissociation (CAD) and sustained off-resonance
      collisionally activated dissociation (SORI-CAD) spectra are explained as a
      consequence of the excitation process. The advantages and disadvantages of the
      three techniques are discussed within the context of structural elucidation.

PMID- 14673831
TI  - High-precision measurements of 17O/16O and 18O/16O of O2 and O2/Ar ratio in air.
AB  - A method for high-precision and high-accuracy mass spectrometric measurements of
      the ratios among the three oxygen isotopes, and of the O(2)/Ar ratio, is
      presented. It involves separation of the O(2)-Ar mixture from air and includes a
      fully automated system that ensures highly reliable sample processing. Repeated
      measurements of atmospheric oxygen yield the repeatability (+/-SE x t, standard
      error of the mean (n = 12) multiplied by Student's t-factor for a 95% confidence
      limit) of 0.004, 0.003 and 0.2 per thousand for delta(18)O, delta(17)O and delta
      O(2)/Ar, respectively.

PMID- 14673832
TI  - Ionization enhancement in atmospheric pressure chemical ionization and
      suppression in electrospray ionization between target drugs and stable-isotope
      labeled internal standards in quantitative liquid chromatography/tandem mass
      spectrometry.
AB  - The phenomena of ionization suppression in electrospray ionization (ESI) and
      enhancement in atmospheric pressure chemical ionization (APCI) were investigated
      in selected-ion monitoring and selected-reaction monitoring modes for nine drugs
      and their corresponding stable-isotope-labeled internal standards (IS). The
      results showed that all investigated target drugs and their co-eluting isotope
      labeled IS suppress each other's ionization responses in ESI. The factors
      affecting the extent of suppression in ESI were investigated, including
      structures and concentrations of drugs, matrix effects, and flow rate. In
      contrast to the ESI results, APCI caused seven of the nine investigated target
      drugs and their co-eluting isotope-labeled IS to enhance each other's ionization
      responses. The mutual ionization suppression or enhancement between drugs and
      their isotope-labeled IS could possibly influence assay sensitivity,
      reproducibility, accuracy and linearity in quantitative liquid
      chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass
      spectrometry (LC/MS/MS). However, calibration curves were linear if an
      appropriate IS concentration was selected for a desired calibration range to keep
      the response factors constant.

PMID- 14673833
TI  - Sialylation analysis of O-glycosylated sialylated peptides from urine of patients
      suffering from Schindler's disease by Fourier transform ion cyclotron resonance
      mass spectrometry and sustained off-resonance irradiation collision-induced
      dissociation.
AB  - A strategy based on Fourier transform ion cyclotron resonance mass spectrometry
      (FTICR-MS) for screening of complex glycoconjugate mixtures containing O-linked
      glycopeptides and O-glycosylated amino acids with alpha-N-acetylgalactosaminyl
      residues is presented. To detect and identify O-glycoforms present in urine of
      patients suffering from hereditary N-acetylhexosaminidase deficiency (known as
      Schindler's disease), present at 100 times higher concentrations than in urine of
      healthy controls, new accurate methods for mapping and sequencing were required.
      In the mass spectrometric analysis particular attention has to be paid to
      original sialylation patterns, because of the potential lability of the sialic
      acid moiety during the desorption/ionization process. Negative ion
      nanoelectrospray ionization (nanoESI) FTICR-MS at 9.4 T is shown here to
      represent a method of choice for identification of single components in such
      complex glycomixtures due to high resolution and mass accuracy. By optimization
      of sustained off-resonance irradiation collision-induced dissociation tandem mass
      spectrometry (SORI-CID-MS(2)) in the negative ion mode, the type and sequence of
      the sialylated glycopeptide components were determined from their fragmentation
      patterns. Additionally, implementation of SORI-CID-MS(3) provides detailed
      information for sialylation analysis. The potential diagnostic value of this
      approach is discussed.

PMID- 14673834
TI  - Stable-isotope dilution analysis of galactose metabolites in human erythrocytes.
AB  - An established gas chromatography/mass spectrometry (GC/MS) method, devised for
      stable-isotope dilution analysis of plasma galactose, was developed to allow
      determination of erythrocyte (red blood cell, RBC) concentrations of galactose-1
      phosphate and other primary metabolites relevant in galactosaemia. Galactose-1
      phosphate was enzymatically converted to galactose, and the aldononitrile
      pentaacetate derivative was separated by gas chromatography and determined by
      mass spectrometry using chemical ionisation and selected ion monitoring of the
      [MH-60](+) ion. U-(13)C-Labelled standard was used for quantification.
      Comparative measurements were conducted using established fluorimetric and
      radiometric enzymatic methods. The GC/MS analysis for galactose-1-phosphate was
      linear (range examined 0-600 micromol/L(RBC), packed cells), of acceptable
      repeatability at low and high concentrations (within and between run CVs <15%),
      with a limit of quantification of 0.01 micromol/L(RBC). With samples from
      patients with classical galactosaemia there was a linear correlation with
      conventional enzymatic assays (r(2) > 0.927). In erythrocytes from post
      absorptive patients under treatment, Q188R-heterozygous parents, and healthy
      subjects, galactose-1-phosphate concentrations (mean +/- SD) were found to be 142
      +/- 38 (n = 41), 1.4 +/- 0.2 (n = 8), and 1.9 +/- 0.5 (n = 33) micromol/L(RBC),
      respectively. In comparison, free galactose concentrations were 3.8 +/- 1.7, 0.49
      +/- 0.19, and 0.43 +/- 0.20 mol/L(RBC), respectively. The procedure allowed
      simultaneous galactitol analysis and proved to be useful to trace incorporation
      of (13)C-label into erythrocyte galactose metabolites in a D-[1-(13)C]galactose
      in vivo turnover study.

PMID- 14673835
TI  - The use of nonpolar matrices for matrix-assisted laser desorption/ionization mass
      spectrometric analysis of high boiling crude oil fractions.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOFMS) with nonpolar matrices has been investigated for its applicability
      to the characterization of atmospheric resid crude oil fractions. The data
      obtained by use of nonpolar matrices was compared with that from polar matrices
      as well as from direct LDI-MS and field ionization mass spectrometry. Nonpolar
      matrices, such as anthracene or 9-cyanoanthracene, yield only a single radical
      molecular cation upon LDI. Thus, no interfering matrix-related ions are present
      during the MALDI-TOFMS analysis of the crude oil sample. Nonpolar matrices yield
      molecular mass distributions from linear mode MALDI-TOFMS that are comparable to
      distributions found with LDI-MS. An advantage of nonpolar matrices is the
      increased production of analyte ions, which allows reflectron mode MALDI-TOFMS to
      be performed. Nonpolar matrices are also shown to be less sensitive to solvent
      and sample preparation conditions than conventional polar matrices. These results
      suggest that nonpolar matrices may be favorable alternatives to more traditional
      polar or acidic matrices commonly used in the MALDI mass spectral
      characterization of crude oil related samples.

PMID- 14673836
TI  - On the photo-initiated isomerization of acetonitrile.

PMID- 14673837
TI  - Investigations in chiral reactions: identification of new adducts in the
      reactions of ethyl pyruvate with acetic anhydride and pyridine.

PMID- 14673838
TI  - A simple and reliable method for the determination of nicotine and cotinine in
      teeth by gas chromatography/mass spectrometry.

PMID- 14673841
TI  - Continuous flow techniques in organic synthesis.
AB  - As part of the dramatic changes associated with the need for preparing compound
      libraries in pharmaceutical and agrochemical research laboratories, the search
      for new technologies that allow automation of synthetic processes has become one
      of the main topics. Despite this strong trend for automation high-throughput
      chemistry is still carried out in batches, whereas flow-through processes are
      rather restricted to production processes. This is far from understandable
      because the main advantages of that approach are facile automation,
      reproducibility, safety, and process reliability, because constant reaction
      parameters can be assured. Indeed, methods and technologies are missing that
      allow rapid transfer from the research level to process development without time
      consuming adaptation and optimization of methods from the laboratory scale to
      production plant scale. Continuous-flow processes are considered as a universal
      lever to overcome these restrictions and, only recently, joint efforts between
      synthetic and polymer chemists and chemical engineers have resulted in the first
      continuous-flow devices and microreactors; these allow rapid preparation of
      compounds with minimum workup. Many of these approaches use immobilized reagents
      and catalysts, which are embedded in a structured flow-through reactor. It is
      generally accepted, that for achieving best reaction and kinetic parameters for
      convective-flow processes monolithic materials are ideally suited as solid phases
      or polymer supports. In addition, immobilization techniques have to be developed
      that allow facile regeneration of the active species in the reactor.

PMID- 14673842
TI  - Asymmetric dearomatization of the furan ring promoted by conjugate organolithium
      addition to (menthyloxy)(3-furyl)carbene complexes of chromium.
AB  - The sequential low-temperature addition reaction of an organolithium compound and
      methyl triflate to (menthyloxy)(3-furyl)carbene complexes of chromium and
      tungsten proceeded with excellent regioselectivity (1,4-addition) and
      diastereoselectivity (2,3-trans disposition of the nucleophile and electrophile
      groups) to afford new 2,3-disubstituted (2,3-dihydro-3-furyl)carbene complexes.
      In addition, a high degree of diastereofacial selectivity was achieved by
      employing alkenyllithium compounds. After detachment of both the metal fragment
      and the chiral auxiliary group, trisubstituted 2,3-dihydrofuran derivatives
      containing a quaternary stereogenic center at the C3 position were obtained. The
      characterization, including X-ray crystallography, of a novel type of stable four
      membered chelate (eta(2)-alkene)tetracarbonylcarbene complex of chromium is also
      reported.

PMID- 14673843
TI  - SSZ-53 and SSZ-59: two novel extra-large pore zeolites.
AB  - The syntheses, structure solutions, and physicochemical and catalytic
      characterizations of the novel zeolites SSZ-53 and SSZ-59 are described. SSZ-53
      and SSZ-59 were synthesized under hydrothermal conditions with the [1-(4
      fluorophenyl)cyclopentylmethyl]trimethyl ammonium cation and 1-[1-(4
      chlorophenyl)cyclopentylmethyl]-1-methyl azocanium cation, respectively, as
      structure-directing agents. The framework topology of SSZ-53 was solved with the
      FOCUS method, and the structure of SSZ-59 was determined by model building.
      Rietveld refinement of synchrotron X-ray powder diffraction data confirms each
      proposed model. SSZ-53 and SSZ-59 each possess a one-dimensional channel system
      delimited by 14-membered rings. Results from transmission electron microscopy,
      electron diffraction, catalytic experiments (spaciousness index and constraint
      index tests), and argon and hydrocarbon adsorption experiments are consistent
      with the proposed structures.

PMID- 14673844
TI  - Spectroscopic and computational investigations of stable radical anions of
      triosmium benzoheterocycle clusters.
AB  - The variable temperature (1)H and (13)C NMR and EPR spectra of the stable radical
      anions [Os(3)(CO)(9)(micro(3)-eta(2)-L)(micro-H)] (LH=phenanthridine, 1; 5,6
      benzoquinoline, 2), and [Os(3)(CO)(10)(micro(3)-eta(2)-L)(micro-H)]
      (LH=quinoxaline, 3) are reported. The radical anions 1(-), 2(-), and 3(-) can be
      prepared by both exhaustive electrolysis and partially by chemical reduction with
      cobaltocene and with sodium dispersion (only with sodium dispersion in the case
      of 3(-)). DFT calculations on 1-3 reveal that the LUMO for the electron-deficient
      compounds 1 and 2 involves significant contributions from both the heterocyclic
      ligand and the two metal atoms bridged by the ligand and the micro-hydride. The
      character of this orbital rationalizes the previously observed regioselective
      reactions of these complexes with nucleophiles. In contrast, the LUMO for the
      electron precise 3 involves only ligand-based orbitals. Partial chemical
      reduction of 1 and 2 requires an excess of either cobaltocene or sodium, and
      their (1)H and (13)C NMR spectra reveal selective line broadening of those proton
      resonances that are predicted by DFT calculations to bear the greatest amount of
      free spin density. The variable temperature behavior of the partially chemically
      reduced species of 1 and 2 indicates that electron transfer between the
      reduced/unreduced cluster pair and between the cobaltocene/cobaltocenium pair
      occurs on the NMR timescale. The radical anions of 1 and 2 prepared by exhaustive
      electrolysis show an EPR signal at room temperature, while the NMR signals are
      uniformly broadened. Compound 3 appears to be partially reduced by sodium at room
      temperature and shows uniformly broadened (1)H NMR resonances at room temperature
      that sharpen significantly at -80 degrees C. The temperature dependence of the
      spectra are discussed in terms of the effects of relative electron nuclear
      relaxation processes, chemical exchange, and the results of the DFT calculations.

PMID- 14673845
TI  - A phthalocyanine dendrimer capable of forming spherical micelles.
AB  - A novel and intrinsically spherical micelle has been prepared by utilizing a
      silicon phthalocyanine ((WG3)SiPc) that has a thin hydrophobic alkyl chain and a
      bulky hydrophilic poly(aryl ether) dendrimer with terminal carboxyl groups, as
      its two axial ligands. Gel-permeation chromatography and cryo-transmission
      electron microscopic experiments indicate that (WG3)SiPcs self-assemble to form a
      spherical micelle at very low concentrations in aqueous solution. Depending on
      the pH of the aqueous phase, (WG3)SiPc shuttles between aqueous and organic
      phases. In the presence of hydrophobic molecules, this transfer is accompanied by
      the inclusion of these (guest) molecules, indicating that the micelle acts as a
      molecular capsule with a nanospace surrounded by functional phthalocyanine
      planes.

PMID- 14673846
TI  - Novel heterotopic colloids of anionic porphyrins entangled in cationic
      amphiphilic cyclodextrins: spectroscopic investigation and intracellular
      delivery.
AB  - The entanglement process between water-soluble 5,10,15,20-tetrakis(4
      sulfonatophenyl)-21H,23H-porphine and the amphiphilic cyclodextrin (CD)
      heptakis(2-omega-amino-O-oligo(ethylene oxide)-6-hexylthio)-beta-CD and the
      occurrence of various species at different porphyrin:CD ratios were studied by a
      combination of UV/Vis absorption, fluorescence anisotropy, time-resolved
      fluorescence, resonance light scattering, and circular dichroism. The effect of
      the entanglement process on the mean vesicle diameter was investigated over a
      wide concentration range by quasielastic light-scattering techniques. The
      experimental results indicate that the presence of porphyrins in this colloidal
      system promotes some structural rearrangements, essentially driven by charge
      interaction, which are responsible for a sensitive change of vesicle dimensions.
      In the range of porphyrin:CD molar ratios between 1:10 and 1:50, the porphyrin is
      solubilized in monomeric form (tau(1)=11.5 ns) and photosensitizes the production
      of singlet oxygen ((1)O(2)). At the same molar ratio the ability of this
      amphiphilic cyclodextrin to transport porphyrins into tumor cells indicates
      specificity at the nuclear-compartment level. These findings may be of potential
      interest for the of development agents for photodynamic therapy of tumors.

PMID- 14673847
TI  - Calenzanane sesquiterpenes from the red seaweed Laurencia microcladia from the
      Bay of Calenzana, Elba Island: acid-catalyzed stereospecific conversion of
      calenzanol into indene- and guaiazulene-type sesquiterpenes.
AB  - It is shown here that calenzanane sesquiterpenes (1 and 6) can be isolated from
      organic extracts from the red seaweed Laurencia microcladia Kutzing from the Bay
      of Calenzana, Elba Island, provided contact with acidic media is minimized. Such
      contact induces rearrangements of 1 in dry solvents to indene-type 5 and the blue
      colored guaiazulenium-type ion 17, via spectrometrically (NMR) characterized
      indene-type transient intermediates 10, 14, and 12. Addition of NEt(3) to the
      reaction mixture at appropriate stages allowed the isolation of 12 (and 8 on
      workup on SiO(2)), and guaiazulene (18). Prolonged contact with silica gel led to
      complete degradation of 1, giving calenzanane-type epimeric enones 20 a/20 b as
      well as indene-type epimeric carbinols 22 a/22 b and fulvene 7. The latter was
      also formed during silica-gel flash chromatography of the algal extracts. A
      unifying mechanistic view of these branching and cascade transformations may have
      both heuristic value, suggesting possible artefact origin of azulenoids, and
      synthetic applications.

PMID- 14673848
TI  - Reduction of benzophenone and 9(10H)-anthracenone with the magnesium complex
      [(2,6-iPr2C6H3-bian)Mg(thf)3].
AB  - The reduction of benzophenone with the magnesium complex [(2,6-iPr(2)C(6)H(3)
      bian)Mg(thf)(3)] (1), containing the 1,2-bis[(2,6
      diisopropylphenyl)imino]acenaphthene dianion, affords the pinacolato complex
      [(2,6-iPr(2)C(6)H(3)-bian)Mg(thf)](2)[micro-O(2)C(2)Ph(4)].(C(6)H(6))(4) (2). The
      reaction of 1 with 9(10H)-anthracenone yields the 9-anthracenolato complex [(2,6
      iPr(2)C(6)H(3)-bian)Mg(OC(14)H(9))(thf)(2)] (3). Complexes 2 and 3 were
      characterized by elemental analyses, UV/Vis, IR, and ESR spectroscopy, as well as
      by single crystal X-ray diffraction. Complex 2 dissociates in solution with
      splitting of the bridging pinacolato unit, forming the biradical diimino/ketyl
      complex [(2,6-iPr(2)C(6)H(3)-bian)Mg(thf)(OCPh(2))].

PMID- 14673849
TI  - Novel synthetic approach for optical resolution of cryptophanol-A: a direct
      access to chiral cryptophanes and their chiroptical properties.
AB  - The separation by crystallization of the pair of cryptophane diastereomers 1 a
      and 1 b, obtained in 1:1 ratio by treating racemic anti cryptophanol-A (2) with (
      )-camphanic acid chloride, provided a substantial amount of optically pure
      material (diastereomeric excess>98 %). Subsequent hydrolysis afforded the
      optically pure cryptophanol-A enantiomers (+)-2 and (-)-2, which were submitted
      to nucleophilic substitution reactions to provide cryptophane-A (+)-3 and
      cryptophane monoester (-)-4 in optically pure form. The chiroptical properties of
      the new cryptophanes 1-4 were investigated by using circular dichroism
      spectroscopy, and the absolute configuration of the molecules was clearly
      established. These new cryptophanes represent additional interesting examples for
      studying the Cotton effect of interacting multichromophoric systems. Moreover,
      this novel approach presents numerous advantages over the other methods developed
      so far to obtain optically pure cryptophanes, and compounds (-)-2, (+)-2, and (-)
      4 can give access to new enantiopure functionalized cryptophanes with host-guest
      properties similar to those of cryptophane-A.

PMID- 14673850
TI  - Ruthenium-catalyzed chemoselective N-allyl cleavage: novel Grubbs carbene
      mediated deprotection of allylic amines.
AB  - A novel application of the Grubbs carbene complex has been discovered. The first
      examples of the catalytic deprotection of allylic amines with reagents other than
      palladium catalysts have been achieved through Grubbs carbene mediated reaction.
      Significantly, the catalytic system directs the reaction toward the selective
      deprotection of allylic amines (secondary as well as tertiary) in the presence of
      allylic ethers. A variety of substrates, including enantiomerically pure
      multifunctional piperidines, are also usable. The new method is more convenient,
      chemoselective, and operationally simple than the palladium-catalyzed method. The
      current mechanistic hypothesis invokes a nitrogen-assisted ruthenium-catalyzed
      isomerization, followed by hydrolysis of the enamine intermediate. We believe
      that the reactive species involved in the reaction may be an Rubond;H species
      rather than the Grubbs carbene itself. Thus, the isomerization may occur
      according to the hydride mechanism. The synthetic utility of this ruthenium
      catalyzed allyl cleavage is illustrated by the preparation of indolizidine-type
      alkaloids.

PMID- 14673851
TI  - Fragmentation of carbohydrate anomeric alkoxy radicals: a new synthesis of chiral
      1-halo-1-iodo alditols.
AB  - Treatment of 1,2-fluorohydrins, 1,2-chlorohydrins, 1,2-bromohydrins, and 1,2
      iodohydrins of the D-gluco, D-galacto, D-lacto, L-rhamno, D-allo, L-arabino, 3
      deoxy-D-gluco, and 3,4-dideoxy-D-gluco families of carbohydrates with the
      (diacetoxyiodo)benzene/iodine system afforded 1-fluoro-1-iodo, 1-chloro-1-iodo, 1
      bromo-1-iodo, and 1,1-diiodo alditols, respectively, in excellent yields. The
      reaction was achieved by radical fragmentation of the C1bond;C2 bond, triggered
      by the initially formed anomeric alkoxy radical, and subsequent trapping of the
      C2-radical by iodine atoms. This methodology is compatible with the stability of
      the protective groups most frequently used in carbohydrate chemistry. The
      potential utility of these 1-halo-1-iodo alditols as chiral synthons was
      evaluated by their transformation into alk-1-enyl iodides and in the Takai E
      olefination reaction.

PMID- 14673852
TI  - Kinetics of aquation and anation of ruthenium(II) arene anticancer complexes,
      acidity and X-ray structures of aqua adducts.
AB  - The aqua adducts of the anticancer complexes [(eta(6)-X)Ru(en)Cl][PF(6)]
      (X=biphenyl (Bip) 1, X=5,8,9,10-tetrahydroanthracene (THA) 2, X=9,10
      dihydroanthracene (DHA) 3; en=ethylenediamime) were separated by HPLC and
      characterised by mass spectrometry as the products of hydrolysis in water. The X
      ray structures of the aqua complexes [(eta(6)-X)Ru(en)Y][PF(6)](n), X=Bip, Y=0.5
      H(2)O/0.5 OH, n=1.5 (4), X=THA, Y=0.5 H(2)O/0.5 OH, n=1.5 (5 A), X=THA, Y=H(2)O,
      n=2 (5 B), and X=DHA, Y=H(2)O, n=2 (6), are reported. In complex 4 there is a
      large propeller twist of 45 degrees of the pendant phenyl ring with respect to
      the coordinated phenyl ring. Although the THA ligand in 5 A and 5 B is relatively
      flat, the DHA ring system in 6 is markedly bent (hinge bend ca. 35 degrees ) as
      in the chloro complex 3 (41 degrees ). The rates of aquation of 1-3 determined by
      UV/Vis spectroscopy at various ionic strengths and temperatures (1.23-2.59x10(-3)
      s(-1) at 298 K, I=0.1 M) are >20x faster than that of cisplatin. The reverse,
      anation reactions were very rapid on addition of 100 mM NaCl (a similar
      concentration to that in blood plasma). The aquation and anation reactions were
      about two times faster for the DHA and THA complexes compared to the biphenyl
      complex. The hydrolysis reactions appear to occur by an associative pathway. The
      pK(a) values of the aqua adducts were determined by (1)H NMR spectroscopy as 7.71
      for 4, 8.01 for 5 and 7.89 for 6. At physiologically-relevant concentrations (0.5
      5 microM) and temperature (310 K), the complexes will exist in blood plasma as
      >89 % chloro complex, whereas in the cell nucleus significant amounts (45-65 %)
      of the more reactive aqua adducts would be formed together with smaller amounts
      of the hydroxo complexes (9-25 %, pH 7.4, [Cl(-)]=4 mM).

PMID- 14673853
TI  - (9Z)- and (11Z)-8-methylretinals for artificial visual pigment studies:
      stereoselective synthesis, structure, and binding models.
AB  - Artificial visual pigment formation was studied by using 8-methyl-substituted
      retinals in an effort to understand the effect that alkyl substitution of the
      chromophore side chain has on the visual cycle. The stereoselective synthesis of
      the 9-cis and 11-cis isomers of 8-methylretinal, as well as the 5-demethylated
      analogues is also described. The key bond formations consist of a thallium
      accelerated Suzuki cross-coupling reaction between cyclohexenylboronic acids and
      dienyliodides (C6-C7), and a highly stereocontrolled Horner-Wadsworth-Emmons or
      Wittig condensation (C11-C12). The cyclohexenylboronic acid was prepared by
      trapping the precursor cyclohexenyllithium species with B(OiPr)(3) or B(OMe)(3).
      The cyclohexenyllithium species is itself obtained by nBuLi-induced elimination
      of a trisylhydrazone (Shapiro reaction), or depending upon the steric hindrance
      of the ring, by iodine-metal exchange. In binding experiments with the apoprotein
      opsin, only 9-cis-5-demethyl-8-methylretinal yielded an artificial pigment; 9-cis
      8-methylretinal simply provided residual binding, while evidence of artificial
      pigment formation was not found for the 11-cis analogues. Molecular-mechanics
      based docking simulations with the crystal structure of rhodopsin have allowed us
      to rationalize the lack of binding displayed by the 11-cis analogues. Our results
      indicate that these isomers are highly strained, especially when bound, due to
      steric clashes with the receptor, and that these interactions are undoubtedly
      alleviated when 9-cis-5-demethyl-8-methylretinal binds opsin.

PMID- 14673854
TI  - Quantitative chirality analysis of molecular subunits of bis(oxazoline)copper(II)
      complexes in relation to their enantioselective catalytic activity.
AB  - The analysis of the quantitative chirality of molecular subunits of spirocyclic
      bisoxazoline copper complexes was carried out in order to identify the molecular
      portions most responsible for the chirality of the whole molecule, and therefore
      also for its catalytic enantioselectivity. It is shown that the smallest fragment
      that carries the information on molecular chirality contains only a portion of
      the bidentate bisoxazoline ligands and most atoms of the two monodentate ligands.
      The structural parameters that are best correlated to the chirality measures of
      the studied systems are the bond angles at the bridgehead spiro-carbon atom. A
      prediction is made for an analogous catalyst with potentially high
      enatioselectivity.

PMID- 14673855
TI  - Molecular dynamics simulations of small peptides: can one derive conformational
      preferences from ROESY spectra?
AB  - Folding properties of beta-peptides were investigated by means of NMR experiments
      and MD simulations of beta-dipeptides, which serve as small test systems to study
      the influence of stereocenters and side chains on hydrogen-bond and consequently
      on secondary-structure formation. Two stereoisomers, SR and SS, of a Val-Phe
      dipeptide, and of the corresponding Ala-Ala dipeptide, and a Gly-Gly dipeptide
      were simulated in methanol for 40 ns. In agreement with experiment, the isomers
      of the Val-Phe dipeptide adopt quite different conformers at 298 K, the
      differences being reduced at 340 K. Interestingly, the SR isomer shows enhanced
      hydrogen bonding at the higher temperature. The adopted conformations are
      primarily determined by the R or S side chain substitution, and less by the type
      of side chain. Back-calculation of (1)H ROESY spectra and (3)J coupling constants
      from the MD simulations and comparison with the experimental data for the Val-Phe
      dipeptides shows good agreement between simulation and experiment, and reveals
      possible problems and pitfalls, when deriving structural properties of a small
      and extremely flexible molecule from NMR data only. Inclusion of all aspects of
      internal dynamics is essential to the correct prediction of the NMR spectra of
      these small molecules. Cross comparison of calculated with experimental spectra
      for both isomers shows that only a few out of many ROESY peaks reflect the
      sizeable conformational differences between the isomers at 298 K.

PMID- 14673856
TI  - Unique guest-inclusion properties of a breathing ionic crystal of
      K3[Cr3O(OOCH)6(H2O)3][alpha-SiW12O40].16 H2O.
AB  - A microstructured ionic crystal, K(3)[Cr(3)O(OOCH)(6)(H(2)O)(3)][alpha
      SiW(12)O(40)].16 H(2)O (1) was synthesized by the complexation of the Keggin-type
      polyoxometalate of [alpha-SiW(12)O(40)](4-) with a macrocation of
      [Cr(3)O(OOCH)(6)(H(2)O)(3)](+). Compound 1 possessed a straight channel, with an
      opening of approximately 0.5x0.8 nm, which contained the water of
      crystallization. The use of the macrocation with large size (0.7 nm) and small
      charge (+1) reduced the anion-cation interaction and was essential for the
      channel formation. The molecular structures of the polyoxometalate and the
      macrocation in 1 were retained under vacuum at 473 K. Analogues of 1 were
      synthesized with [alpha-PVW(11)O(40)](4-) or [Fe(3)O(OOCH)(6)(H(2)O)(3)](+). The
      water of crystallization in 1 was removed under vacuum at room temperature to
      form the closely packed guest-free phase 2. Compound 2 reversibly and repeatedly
      included water and polar organic molecules with two carbon atoms or less. Guest
      inclusion was highly selective and a difference of even one methylene group in
      the organic guest molecule was discriminated by the host. Polar organic molecules
      with longer methylene chains and nonpolar molecules such as dinitrogen and
      methane were completely excluded. The guest-inclusion properties could be
      explained by the ion-dipole interaction between the host and the guest, which is
      proportional to the dipole moment of the guest molecule and inversely
      proportional to the ion-dipole (host-guest) distance. Thus, small polar molecules
      were selectively absorbed. These distinctive guest-inclusion properties were
      successfully applied to the oxidation of methanol from a mixture of C(1) and C(2)
      alcohols. These results show unique guest inclusion and catalysis by rationally
      designed ionic crystals.

PMID- 14673857
TI  - Theoretical study of rhodium(I) carbene complexes: the structural versatility of
      phosphino- compared with aminocarbenes.
AB  - Density functional calculations are reported for complexes of general formula
      [(carbene)RhClL(2)] featuring model phosphino- and aminocarbenes. Both the cis
      and trans isomers of the rhodium(I) eta(1)-complexes (1-9) were investigated, and
      the influence of the rhodium co-ligands (L=ethylene, phosphine, or carbon
      monoxide) was evaluated. In the case of phosphinocarbenes and carbon monoxide as
      a ligand, a somewhat unusual coordination mode was observed, in which a
      significant intramolecular Cl-->C(carbene) interaction is present. The propensity
      of phosphino- and aminocarbenes to behave as four electron donors was also
      investigated both structurally and energetically on the related eta(2)-complexes
      10-18. These results as a whole emphasize the structural versatility of phosphino
      compared with aminocarbene complexes.

PMID- 14673858
TI  - LaSeTe2-temperature dependent structure investigation and electron holography on
      a charge-density-wave-hosting compound.
AB  - Single crystals of LaSeTe(2) have been prepared by reaction of the elements in a
      LiCl/RbCl flux at 970 K for seven days. Satellite reflections observed in
      diffraction experiments indicate the presence of an incommensurate lattice
      distortion, which is of the charge-density-wave (CDW) type. The modulated
      structure has been solved from X-ray data at 173, 293, and 373 K. LaSeTe(2)
      crystallizes in the 3+1-dimensional orthorhombic superspace group
      Cmcm(00gamma)s00 (No. 63.2) with lattice parameters of a=4.295(1), b=25.371(4),
      c=4.306(1) A (173 K), a=4.297(1), b=25.408(4), c=4.309(1) A (293 K), and
      a=4.309(1), b=25.481(6), c=4.321(1) A (373 K). The modulation vector q=(0, 0,
      0.288) does not change over the temperature interval. Electron holographic
      investigations confirm the existence of the modulation and help to visualize the
      charge-density wave.

PMID- 14673859
TI  - Comparison of micro- and mesoporous inorganic materials in the uptake and release
      of the drug model fluorescein and its analogues.
AB  - The uptake of the three species of the drug model fluorescein (fluorescein sodium
      salt (FNa), fluorescein free acid (F), and fluorescein diacetate (FDA)) by
      zeolite NaX and the mesoporous zeotype MCM-41 was investigated as well as their
      release rates into solutions at pH 7 and pH 4.5. UV/Vis analysis was carried out
      at a wavelength of 490 nm. Uptakes of the sodium salt of 9 % for zeolite X and 14
      % for MCM suggest little penetration of the pores. The use of ethanol as the
      loading solvent for F resulted in little uptake for both zeolitic materials due
      to the successful competition of the ethanol for binding sites. Use of acetone
      (weaker proton acceptor) as loading solvent significantly improved the uptake of
      F to 17 % and 12 % for zeolite X and MCM, respectively, whilst the uptake of FDA
      in acetone increased still further to 22 % and 17 % for zeolite X and MCM,
      respectively. Generally there was a large initial release of the fluorescein
      analogues from the surface of the zeolites with very little further increase over
      time. The prescence of an esterase enzyme in the release medium of FDA tripled
      the release from MCM to 15 % but left the release from zeolite X unaffected at 6
      %. The results obtained show that uptake of fluorescein and its analogues is
      dependent on the loading solvent used, the amount released is influenced by not
      only the solvent but the pH and the presence of enzymes in the release medium.

PMID- 14673860
TI  - A functionalized noncovalent macrocyclic multiporphyrin assembly from a
      dizinc(II) bis-porphyrin receptor and a free-base dipyridylporphyrin.
AB  - The bis-porphyrin system ZnP(2), in which two zinc porphyrins are connected by a
      phenanthroline linker in an oblique fashion, acts as a bifunctional receptor
      towards the complexation of free-base meso-5,10-bis(4'-pyridyl)-15,20
      diphenylporphyrin (4'-cis DPyP). In solution, NMR spectroscopy evidenced
      quantitative formation of the tris-porphyrin macrocyclic assembly ZnP(2)(4'-cis
      DPyP), in which the two fragments are held together by two axial 4'-N(pyridyl)-Zn
      interactions. The remarkable stability of the edifice (an association constant of
      about 6x10(8) M(-1) was determined by UV/Vis absorption and emission titration
      experiments in toluene) is due to the almost perfect geometrical match between
      the two interacting units. The macrocycle was crystallized and studied by X-ray
      diffraction, which confirmed the excellent complementarity of the two components.
      Photoinduced energy transfer from the singlet excited state of the zinc porphyrin
      chromophores to the free-base porphyrin occurs with an efficiency of 98 %
      (k(en)=2x10(10) s(-1) in toluene, ambient temperature) with a mechanism
      consistent with a dipole-dipole process with a low orientation factor.

PMID- 14673861
TI  - Synthesis and inhibition properties of conformational probes for the mutase
      catalyzed UDP-galactopyranose/furanose interconversion.
AB  - UDP-galactose mutase is a flavoenzyme that catalyzes the isomerization of UDP
      galactopyranose into UDP-galactofuranose, a key step in the biosynthesis of
      important bacterial oligosaccharides. Several mechanisms for this unique ring
      contraction have been proposed, one of them involving a putative 1,4
      anhydrogalactopyranose as an intermediate in the reaction. The purpose of this
      study was to probe the mutase binding site with conformationally restricted
      analogues of its substrate. Thus, we describe the straightforward synthesis of
      two C-glycosidic UDP-galactose derivatives: analogue 1, presenting a galactose
      moiety locked in a bicyclic (1,4)B boat conformation, and UDP-C-Galf 2, where the
      galactose residue is locked in the conformation of the mutase substrate. The two
      molecules were found to be inhibitors of UDP-galactose mutase at levels depending
      on the redox state of the enzyme. Strong inhibition of the native enzyme, but a
      low one of the reduced mutase, were observed with UDP-C-Galf 2, whereas 1
      displayed intermediate inhibition levels under both native and reducing
      conditions. These data provide evidence of a significant conformational
      difference of the mutase binding pocket in the reduced enzyme and in the native
      one, the enzyme switching from a low Galf-affinity state (reduced enzyme) to a
      very strong one (native enzyme). It is remarkable that the mutase binds the boat
      locked analogue 1 with similar affinities in both its conformational states.
      These results support a mechanism involving the formation of 1,4
      anhydrogalactopyranose as a low-energy intermediate. An alternative explanation
      would be that the distortion of the galactose moiety during the cycle contraction
      transiently brings the carbohydrate into a conformation close to a (1,4)B boat.

PMID- 14673862
TI  - Lanthanide(III) complexes of novel mixed carboxylic-phosphorus acid derivatives
      of diethylenetriamine: a step towards more efficient MRI contrast agents.
AB  - Three novel phosphorus-containing analogues of H(5)DTPA (DTPA =
      diethylenetriaminepentaacetate) were synthesised (H6L1, H5L2, H5L3). These
      compounds have a -CH2-P(O)(OH)-R function (R = OH, Ph, CH2NBn2) attached to the
      central nitrogen atom of the diethylenetriamine backbone. An NMR study reveals
      that these ligands bind to lanthanide(III) ions in an octadentate fashion through
      the three nitrogen atoms, a P-O oxygen atom and four carboxylate oxygen atoms.
      The complexed ligand occurs in several enantiomeric forms due to the chirality of
      the central nitrogen atom and the phosphorus atom upon coordination. All
      lanthanide complexes studied have one coordinated water molecule. The residence
      times (tau(M)298) of the coordinated water molecules in the gadolinium(III)
      complexes of H6L1 and H5L2 are 88 and 92 ns, respectively, which are close to the
      optimum. This is particularly important upon covalent and noncovalent attachment
      of these Gd(3+) chelates to polymers. The relaxivity of the complexes studied is
      further enhanced by the presence of at least two water molecules in the second
      coordination sphere of the Gd(3+) ion, which are probably bound to the
      phosphonate/phosphinate moiety by hydrogen bonds. The complex [Gd(L3)(H2O)](2-)
      shows strong binding ability to HSA, and the adduct has a relaxivity comparable
      to MS-325 (40 s(-1) mM(-1) at 40 MHz, 37 degrees C) even though it has a less
      favourable tau(M) value (685 ns). Transmetallation experiments with Zn(2+)
      indicate that the complexes have a kinetic stability that is comparable to-or
      better than-those of [Gd(dtpa)(H2O)](2-) and [Gd(dtpa-bma)(H2O)].

PMID- 14673863
TI  - Theoretical studies on the mode of inhibition of ribonucleotide reductase by 2'
      substituted substrate analogues.
AB  - Several 2'-substituted-2'-deoxyribonucleotides are potent time-dependent
      inactivators of the enzyme ribonucleotide reductase (RNR), which function by
      destructing its essential tyrosil radical and/or by performing covalent addition
      to the enzyme. The former leads to inhibition of the R2 dimer of RNR and the
      latter to inhibition of the R1 dimer. Efforts to elucidate the mechanism of
      inhibition have been undertaken in the last decades, and a general mechanistic
      scheme has emerged. Accordingly, two alternative pathways lead either to the
      inhibition of R1 or R2, for which the 2'-chloro-2'-deoxynucleotides serve as the
      model for the inhibition of R1 and the 2'-azido-2'-deoxynucleotides the model for
      the inhibition of R2. However, the underlying reason for the different behavior
      of the inhibitors has remained unknown until now. Moreover, a fundamental
      mechanistic alternative has been proposed, based on results from biomimetic
      reactions, in which the 2'-substituents would be eliminated as radicals, and not
      as anions, as previously assumed. This would lead to further reactions not
      predicted by the existing mechanistic scheme. To gain a better understanding we
      have performed high-level theoretical calculations on the active site of RNR.
      Results from this work support the general Stubbe's paradigm, although some
      changes to that mechanism are necessary. In addition, a rational explanation of
      the factors that determine which of the dimers (R1 or R2) will be inactivated is
      provided for the first time. It has been demonstrated also that the 2'
      substituents are indeed eliminated as anions, and not as radicals. Biomimetic
      experiments have led to different results because they lack a basic group capable
      of deprotonating the 3'-HO group of the substrate. It has been found here that
      the chemical character of the leaving group (radical or anionic) can be
      manipulated by controlling the protonation state of the 3'-HO group.

PMID- 14673864
TI  - Design of photoactivated DNA oxidizing agents: synthesis and study of
      photophysical properties and DNA interactions of novel viologen-linked acridines.
AB  - A new series of photoactivated DNA oxidizing agents in which an acridine moiety
      is covalently linked to viologen by an alkylidene spacer was synthesized, and
      their photophysical properties and interactions with DNA, including DNA cleaving
      properties, were investigated. The fluorescence quantum yields of the viologen
      linked acridines were found to be lower than that of the model compound 9
      methylacridine (MA). The changes in free energy for the electron transfer
      reactions were found to be favorable, and the fluorescence quenching observed in
      these systems is explained by an electron transfer mechanism. Intramolecular
      electron transfer rate constants were calculated from the observed fluorescence
      quantum yields and singlet lifetime of MA and are in the range from 1.06x10(10)
      s(-1) for 1 a (n=1) to 6x10(8) s(-1) for 1 c (n=11), that is, the rate decreases
      with increasing spacer length. Nanosecond laser flash photolysis of these systems
      in aqueous solutions showed no transient absorption, but in the presence of
      guanosine or calf thymus DNA, transient absorption due to the reduced viologen
      radical cation was observed. Studies on DNA binding demonstrated that the
      viologen-linked acridines bind effectively to DNA in both intercalative and
      electrostatic modes. Results of PM2 DNA cleavage studies indicate that, on
      photoexcitation, these molecules induce DNA damage that is sensitive to
      formamidopyrimidine DNA glycosylase. These viologen-linked acridines are quite
      stable in aqueous solutions and oxidize DNA efficiently and hence can be useful
      as photoactivated DNA-cleaving agents which function purely by the co
      sensitization mechanism.

PMID- 14673865
TI  - Homo- and heterometallic [2x2] grid arrays containing RuII, OsII, and FeII
      subunits and their mononuclear RuII and OsII precursors: synthesis, absorption
      spectra, redox behavior, and luminescence properties.
AB  - The absorption spectra, redox behavior, and luminescence properties (both at 77 K
      in rigid matrices and at room temperature in fluid solution) of a series of [2x2]
      molecular grids have been investigated. The latter were prepared either by means
      of sequential self-assembly, or by a stepwise protection/deprotection procedure,
      and are based on a ditopic hexadentate ligand 1 in which two terpyridine-like
      binding sites are fused together in a linear arrangement. The molecular grids
      studied include the homometallic species [[Fe(1)](4)](8+) (Fe(2)Fe(2)), and the
      heterometallic species [[Ru(1)](2)[Fe(1)](2)](8+) (Ru(2)Fe(2)) and
      [[Os(1)](2)[Fe(1)](2)](8+) (Os(2)Fe(2)). For comparison purposes, the properties
      of the mononuclear complexes [Ru(1)(2)](2+) (1-Ru) and [Os(1)(2)](2+) (1-Os) have
      been studied. All these compounds exhibit very intense absorption bands in the UV
      region (epsilon in the 10(5)-10(6) M(-1) cm(-1) range, attributed to spin-allowed
      ligand-centered (LC) transitions), as well as intense metal-to-ligand charge
      transfer (MLCT) transitions (epsilon in the 10(4)-10(5) M(-1) cm(-1) range) that
      extend to the entire visible region. The mononuclear species 1-Ru and 1-Os
      exhibit relatively intense luminescence, both in acetonitrile at room temperature
      (tau=59 and 18 ns, respectively) and in butyronitrile rigid matrices at 77 K. In
      contrast, the tetranuclear molecular grids do not exhibit any luminescence,
      either at room temperature or at 77 K. This is attributed to fast intercomponent
      energy transfer from the Ru- or Os-based subunits to the low-lying metal-centered
      (MC) levels involving the Fe(II) centers, which leads to fast radiationless
      decay. The redox behavior of the compounds is characterized by several metal
      centered oxidation and ligand-centered reduction processes, most of them
      reversible in nature (as many as twelve for Fe(2)Fe(2)). Detailed assignment of
      each redox process has been made, and it is apparent that these systems can be
      viewed as multilevel molecular electronic species capable of reversibly
      exchanging a number of electrons at accessible and predetermined potentials.
      Furthermore, it is shown that the electronic interaction between specific
      subunits depends on their location in the structure and on the oxidation states
      of the other components.

PMID- 14673868
TI  - Genetic toxicity of methamphetamine in vitro and in human abusers.
AB  - Methamphetamine (METH) is a widely abused psychomotor stimulant. Although
      numerous studies have examined METH-induced neurotoxicity, its ability to produce
      genotoxic effects has not been evaluated. In this article, we report on the
      genotoxicity of METH in vitro and in human METH abusers. METH induced his(+)
      revertants in Salmonella typhimurium strains TA98 and TA100, and increased the
      frequency of hprt mutants, micronuclei, and sister chromatid exchange (SCE) in
      cultured Chinese hamster ovary K1 (CHO-K1) cells. These METH-induced genotoxic
      effects were eliminated if METH exposure was conducted in the presence of rat
      liver S9, indicating that the genotoxicity was caused by METH, and not by
      metabolites of METH. In addition, reactive oxygen species (ROS) scavengers
      inhibited the METH-induced micronuclei in CHO-K1 cells. Further investigation
      with 76 human long-term METH abusers and 98 unexposed controls demonstrated that
      total METH exposure correlated with micronucleus and SCE frequencies in cultured
      lymphocytes. The results of this study indicate that METH is a genotoxic agent
      and that ROS may play a role in METH-induced genotoxicity.

PMID- 14673869
TI  - Modulation of plasma lipid levels affects benzo[a]pyrene-induced DNA damage in
      tissues of two hyperlipidemic mouse models.
AB  - The role of plasma lipids in the uptake, transportation, and distribution of
      lipophilic carcinogens like benzo[a]pyrene (B[a]P) remains unclear. Therefore, we
      studied the effects of dietary-modulated plasma lipids on B[a]P-induced DNA
      damage in several organs of two hyperlipidemic mouse models. Male apolipoprotein
      E (ApoE)*3-Leiden (n = 22) and ApoE knockout (ApoE-KO) mice (n = 20) were fed a
      high-fat cholesterol (HFC) diet or low-fat cholesterol (LFC; standard mouse chow)
      diet for 3 weeks, after which the animals were exposed to a single oral dose of 5
      mg/kg bw B[a]P or vehicle and killed 4 days later. Plasma lipids were determined
      and DNA adducts were measured in aorta, heart, lung, liver, brain, and stomach.
      Total cholesterol and low-density lipoprotein (LDL) cholesterol were increased in
      all animals on a HFC diet, whereas a decrease of triglycerides was seen only in
      the ApoE-KO mice. In ApoE-KO mice on a normal diet, DNA-adduct levels were
      highest in aorta (10.8 +/- 1.4 adducts/10(8) nucleotides), followed by brain (7.8
      +/- 1.3), lung (3.3 +/- 0.7), heart (3.1 +/- 0.6), liver (1.5 +/- 0.2) and
      stomach (1.2 +/- 0.2). In the ApoE*3-Leiden mice, adduct levels were equally high
      in aorta, heart, and lung (4.6 +/- 0.7, 5.0 +/- 0.5 and 4.6 +/- 0.4,
      respectively), followed by stomach (2.7 +/- 0.4), brain (2.3 +/- 0.2), and liver
      (1.7 +/- 0.2). In the ApoE-KO mice, the HFC diet intervention resulted in lower
      adduct levels in lung (2.1 +/- 0.2), heart (1.9 +/- 0.2), and brain (2.9 +/-
      0.5), as compared with the LFC group. In contrast, a nonsignificant increase of
      adducts was found in aorta (13.1 +/- 1.5). A similar but nonsignificant trend was
      observed in the ApoE*3-Leiden mice. Multiple regression analysis showed that in
      aorta, DNA adducts were inversely related to plasma triglycerides (P = 0.004) and
      were also modulated by the ApoE genotype (P < 0.001). The results of the present
      study support further investigation into the role of dietary modulation of plasma
      lipids, ApoE, and polycyclic aromatic hydrocarbon exposure on the formation of
      DNA adducts in chronic degenerative diseases.

PMID- 14673870
TI  - Sources of polycyclic aromatic hydrocarbon exposure in non-occupationally exposed
      Koreans.
AB  - Urinary 1-hydroxypyrene (1-OHP), an exposure biomarker for polycyclic aromatic
      hydrocarbons (PAHs), was used to identify potential sources of PAH exposure for
      660 Koreans who were not occupationally exposed to PAHs (65% male; 35% female;
      mean age, 36.5 +/- 11.1 years). In this study, 74% of subjects had detectable
      levels of urinary 1-OHP, with a concentration range of 0.001-3.796 microg/L
      (median, 0.079 microg/L). A backward elimination was conducted: five variables
      were selected with a significance level for removal of P < or = 0.1. The results
      of this study showed that residence in areas with relatively poor environmental
      conditions (Seoul and Suwon) was strongly associated with high concentrations of
      urinary 1-OHP (P = 0.007), while consumption of fried chicken and length of time
      spent outdoors had marginal positive associations with urinary 1-OHP levels (P =
      0.06 and P = 0.09, respectively). Compared with the above three factors, tobacco
      smoking and urinary cotinine levels were poorly associated with urinary 1-OHP (P
      = 0.16 and 0.23, respectively). Pear consumption had an inverse association with
      urinary 1-OHP levels (P < 0.01). Individual variations in urinary 1-OHP
      concentrations were evaluated by considering the subjects' age, sex, and genetic
      polymorphisms in enzymes involved in the metabolism of PAHs. Among the individual
      variations, GSTT1-present subjects showed higher 1-OHP levels than GSTT1-absent
      subjects in cities having 10-microm particulate matter (PM(10)) levels and
      population density lower than those of Seoul and Suwon (P < 0.05). These
      epidemiological results suggest that the above factors that should be considered
      in preventing PAH exposure.

PMID- 14673871
TI  - Three origins of phiX174 am3 revertants in transgenic cell culture.
AB  - Transgenic systems for measuring mammalian mutagenesis often use recoverable
      viral vectors. We hypothesize that mutations in these transgenic systems can
      arise from three different origins of DNA damage and replication errors and that
      these three origins of mutations (in vivo, ex vivo, and in vitro) can be
      differentiated in the PhiX174 am3, cs70 single burst assay (SBA) on the basis of
      burst size (BS). In vivo mutations are fixed in the animal, ex vivo mutations are
      fixed in bacterial cells during recovery of the phage, and in vitro revertants
      arise during the first replications of nonmutant phages under selective
      conditions. PX-2 cells, derived from a homozygous embryo of a PhiX174 transgenic
      mouse, were treated with vehicle or N-ethyl-N-nitrosourea (ENU). An algorithm was
      developed to estimate the BS that resulted in the highest induced revertant
      frequency; the estimate was 56. In vivo revertants were defined as having BS >55,
      ex vivo revertants as having a BS of 13-56, and in vitro revertants as having a
      BS of <14. The frequencies of in vivo revertants at 0, 100, and 200 mg/kg ENU
      were 0.06, 0.36, and 4.10 x 10(-6) (dose response, P = 0.004); ex vivo revertants
      were 0.36, 0.46, and 0.41 x 10(-6) (P = 0.37), and in vitro revertants were 0.39,
      0.46, and 0.41 x 10(-6) (P = 0.55), respectively. These results show that only in
      vivo revertants reflect mutagen treatment. They also provide a basis for
      identifying PhiX174 am3 revertants induced in vivo and may increase the
      sensitivity of the assay for in vivo mutation.

PMID- 14673872
TI  - Barium chromate is cytotoxic and genotoxic to human lung cells.
AB  - Hexavalent chromium (Cr(VI)) compounds are widely accepted as human lung
      carcinogens. However, there have been few investigations of the genotoxicity of
      Cr(VI) in human lung cells. Moreover, our knowledge of the effects of Cr(VI) in
      human lung cells is further limited because the available data generally focus on
      the effects of only lead chromate (PbCrO(4)) and sodium chromate (Na(2)CrO(4)).
      To fully understand these carcinogenic compounds, the genotoxic effects to its
      target cells need to be evaluated for additional Cr(VI) salts. Accordingly, we
      investigated the cytotoxicity and clastogenicity of barium chromate (BC) in a
      human lung cell culture model (WTHBF-6 cells). We found that BC induced
      concentration-dependent cytotoxicity in WTHBF-6 cells, with relative survival of
      88%, 74%, 67%, 12%, 3%, and 0.1% after exposure to 0.01, 0.05, 0.1, 0.5, 1, and 5
      microg/cm(2) BC, respectively. Similarly, the amount of chromosomal damage also
      increased with concentration after a 24-h exposure. Specifically, 0.01, 0.05,
      0.1, and 0.5 microg/cm(2) BaCrO(4) damaged 5%, 9%, 22%, and 49% of metaphase
      cells, with the total damage reaching 5, 10, 28, and 65 aberrations per 100
      metaphases, respectively. Concentrations of 1 and 5 microg/cm(2) BC induced a
      profound cell cycle delay, and no metaphases were observed. The spectrum of
      damage included chromatid and chromosome-type lesions consistent with mechanistic
      events associated with the activation of oncogenes and inactivation of tumor
      suppressor genes. Overall the data indicate that BC is cytotoxic and genotoxic to
      human lung cells.

PMID- 14673873
TI  - DNA end sequestration by DNA-dependent protein kinase and end joining of
      sterically constrained substrates in whole-cell extracts.
AB  - Extracts of Xenopus eggs and of cultured human and hamster cells have the
      capacity to join nonhomologous DNA ends, and all do so with similar specificity.
      To examine the formation of repair complexes on DNA under conditions of end
      joining, end-labeled fragments were incubated with the various extracts and then
      subjected to DNase-I footprinting. Human and Xenopus extracts produced footprints
      virtually identical to that of purified DNA-dependent protein kinase holoenzyme
      (Ku plus DNA-PKcs), with protection of the terminal 28 bp. Extracts of hamster
      cells were more variable, but usually produced a 16-bp footprint, similar to that
      of Ku alone. In all cases a 28-bp holoenzyme-like footprint was associated with
      wortmannin-sensitive end joining, minimal 3'-5' exonucleolytic resection, and a
      predominance of accurate end-joining products. To determine whether the short
      segments of DNA occupied by Ku and DNA-PK were sufficient to support end joining,
      Y-shaped substrates were constructed in which only one arm was available for end
      joining. A Y substrate with a 31-bp arm bearing a partially cohesive 3' overhang
      was accurately joined by a Xenopus egg extract, whereas a substrate with a 21-bp
      arm was not. Surprisingly, a human cell extract did not join the Y substrates at
      all. The results suggest that differences in wortmannin sensitivity and in the
      distribution of in vitro end-joining products may be attributable to the
      variations in the levels of DNA-PKcs in the extracts. In addition, end joining in
      human extracts appears to involve interactions with significantly longer segments
      of DNA than the approximately 28 bp occupied by DNA-PK.

PMID- 14673874
TI  - Deletion, rearrangement, and gene conversion; genetic consequences of chromosomal
      double-strand breaks in human cells.
AB  - Chromosomal double-strand breaks (DSBs) in mammalian cells are usually repaired
      through either of two pathways: end-joining (EJ) or homologous recombination
      (HR). To clarify the relative contribution of each pathway and the ensuing
      genetic changes, we developed a system to trace the fate of DSBs that occur in an
      endogenous single-copy human gene. Lymphoblastoid cell lines TSCE5 and TSCER2 are
      heterozygous (+/-) or compound heterozygous (-/-), respectively, for the
      thymidine kinase gene (TK), and we introduced an I-SceI endonuclease site into
      the gene. EJ for a DSB at the I-SceI site results in TK-deficient mutants in
      TSCE5 cells, while HR between the alleles produces TK-proficient revertants in
      TSCER2 cells. We found that almost all DSBs were repaired by EJ and that HR
      rarely contributes to the repair in this system. EJ contributed to the repair of
      DSBs 270 times more frequently than HR. Molecular analysis of the TK gene showed
      that EJ mainly causes small deletions limited to the TK gene. Seventy percent of
      the small deletion mutants analyzed showed 100- to 4,000-bp deletions with a 0-
      to 6-bp homology at the joint. Another 30%, however, were accompanied by
      complicated DNA rearrangements, presumably the result of sister-chromatid fusion.
      HR, on the other hand, always resulted in non-crossing-over gene conversion
      without any loss of genetic information. Thus, although HR is important to the
      maintenance of genomic stability in DNA containing DSBs, almost all chromosomal
      DSBs in human cells are repaired by EJ.

PMID- 14673875
TI  - Increased transcriptional activity of the CYP3A4*1B promoter variant.
AB  - Numerous single nucleotide polymorphisms (SNPs) have been identified in the human
      genome, yet the functional significance of most is unknown. CYP3A4 is a key
      enzyme in the metabolism of numerous compounds. An A-->G substitution 290 bp
      upstream of the CYP3A4 transcription start site (CYP3A4*1B) has been associated
      with cancer phenotypes, but its phenotypic effects are unclear. To investigate
      the functional significance of CYP3A4*1B, we generated two luciferase reporter
      constructs: 1-kb (denoted L, long) and 0.5-kb (denoted S, short) promoter
      fragments containing either the variant (V(L),V(S)) or the wild-type (W(L), W(S))
      sequences. We evaluated the effect of the variant sequence in the HepG2 and MCF-7
      cell lines, and in primary human hepatocytes from three donors. Reporter
      constructs with the variant sequence had 1.2- to 1.9-fold higher luciferase
      activity than constructs with wild-type sequence in the cell lines (P < 0.0001)
      and hepatocytes (P = 0.021, P = 0.027, P = 0.061). The ratio of transcriptional
      activity for V(S):W(S) was similar to the V(L):W(L) ratio in HepG2 cells, but the
      V(S):W(S) ratio was consistently less than the V(L):W(L) ratio in MCF-7 cells.
      This suggests that CYP3A4 expression is higher from the variant promoter and that
      a repressor sequence may exist in the longer constructs. Electrophoretic mobility
      shift assays demonstrated specific binding of a component of HepG2 nuclear
      extract to both wild-type and variant promoters with consistently higher binding
      affinities to the wild-type sequence. This suggests the existence of a
      transcriptional repressor responsible for the lower CYP3A4*1A activity.
      Therefore, the phenotypic effects of the variant CYP3A4*1B may be associated with
      enhanced CYP3A4 expression due to reduced binding of a transcriptional repressor.

PMID- 14673876
TI  - Induction of micronuclei in proestrus vaginal cells from colchicine- and
      cyclophosphamide-treated rats.

PMID- 14673877
TI  - Role of dopamine transporter imaging in routine clinical practice.
AB  - Functional imaging of the dopamine transporter (DAT) defines integrity of the
      dopaminergic system and has its main clinical application in patients with mild,
      incomplete, or uncertain parkinsonism. Imaging with specific single positron
      emission computerised tomography ligands for DAT (FP-CIT, beta-CIT, IPT, TRODAT)
      provides a marker for presynaptic neuronal degeneration. Striatal uptake
      correlates with disease severity, in particular bradykinesia and rigidity, and
      monitoring of progression assists in clinical trials of potential neuroprotective
      drugs. DAT imaging is abnormal in idiopathic Parkinson's disease, multiple system
      atrophy and progressive supranuclear palsy and does not distinguish between these
      disorders. Dopamine loss is seen even in the earliest clinical presentations of
      true parkinsonism; a normal scan suggests an alternative diagnosis such as
      essential tremor, vascular parkinsonism (unless there is focal basal ganglia
      infarction), drug-induced parkinsonism, or psychogenic parkinsonism. Congruence
      between working clinical diagnosis and DAT imaging increases over time in favour
      of baseline DAT imaging results. Additional applications are characterising
      dementia with parkinsonian features (abnormal results in dementia with Lewy
      bodies, normal in Alzheimer's disease); and differentiating juvenile-onset
      Parkinson's disease (abnormal DAT) from dopa-responsive dystonia (normal DAT).

PMID- 14673878
TI  - Movement disorders in patients with peripheral facial palsy.
AB  - Acute unilateral facial paralysis is usually a benign neurological condition that
      resolves in a few weeks. However, it can also be the source of a transient or
      long-lasting severe motor dysfunction, featuring disorders of automatic and
      voluntary movement. This review is organized according to the two most easily
      recognizable phases in the evolution of facial paralysis: (1). Just after
      presentation of facial palsy, patients may exhibit an increase in their
      spontaneous blinking rate as well as a sustained low-level contraction of the
      muscles of the nonparalyzed side, occasionally leading to blepharospasm-like
      muscle activity. This finding may be due to an increase in the excitability of
      facial motoneurons and brainstem interneurons mediating trigeminofacial reflexes.
      (2). If axonal damage has occurred, axonal regeneration beginning at
      approximately 3 months after the lesion leads inevitably to clinically evident or
      subclinical hyperactivity of the previously paralyzed hemifacial muscles. The
      full-blown postparalytic facial syndrome consists of synkinesis, myokymia, and
      unwanted hemifacial mass contractions accompanying normal facial movements. The
      syndrome has probably multiple pathophysiological mechanisms, including abnormal
      axonal branching after aberrant axonal regeneration and enhanced facial
      motoneuronal excitability. Although the syndrome is relieved with local
      injections of botulinum toxin, fear of such uncomfortable contractions may lead
      the patients to avoid certain facial movements, with the implications that this
      behavior might have on their emotional expressions.

PMID- 14673879
TI  - Chronic treatment with small doses of cabergoline prevents dopa-induced
      dyskinesias in parkinsonian monkeys.
AB  - Levodopa continues to be the most effective agent for the symptomatic treatment
      of Parkinson's disease (PD). But over time, initial benefits decline in efficacy
      because of a rise in adverse effects such as dyskinesias. The pathophysiology of
      levodopa-induced dyskinesias (LID) is not completely understood, but it appears
      to result from deficient regulation by dopamine of corticostriatal glutamatergic
      inputs leading to a cascade of neurochemical changes in the striatum and the
      output pathways. In the present study, we examined if the addition of small doses
      of cabergoline (a long-acting D(2) receptor agonist) to levodopa could prevent
      LID. The major hypothesis is that sustained activation of postsynaptic D(2)
      receptors on medium spiny neurons even by small doses of cabergoline could
      prevent or reduce LID. The minor hypothesis, and the more controversial of the
      two, is that the long-acting stimulation by small doses of cabergoline could
      diminish the release of glutamate by the corticostriatal pathway and prevent LID.
      Eight MPTP-treated monkeys with a long-standing and stable parkinsonian syndrome
      and having never received dopaminergic agents were used. Two groups of four were
      treated for 1 month with levodopa/benserazide administered orally (100 mg/25 mg).
      The second group received in addition a threshold dose of cabergoline (dose
      ranging from 0.015 to 0.035 mg/kg, SC). During the treatment, we observed LID in
      the levodopa group but not in the group receiving levodopa+cabergoline.
      Furthermore, the combination produced a comparable antiparkinsonian effect in
      terms of quality but prolonged the duration (by 1 to 2 hours) and increased the
      locomotion (mean for 2 weeks congruent with 104%). Our data suggest that a small
      dose of a long-acting D(2) agonist combined with high doses of levodopa could be
      preventive of LID in patients with PD and could be an alternative to using
      antiglutamatergic agents for this purpose.

PMID- 14673880
TI  - Embryonic mesencephalic grafts increase levodopa-induced forelimb hyperkinesia in
      parkinsonian rats.
AB  - Recent observations from clinical trials of neural grafting for Parkinson's
      disease (PD) have demonstrated that grafted dopamine neurons can worsen
      dyskinesias in some graft recipients. This deleterious side effect reveals a new
      challenge for neural transplantation, that of elucidating mechanisms underlying
      these postgraft dyskinesias. One problem facing this challenge is the
      availability of a cost-effective and reliable animal model in which to pursue
      initial investigations. In the current study, we investigated the interaction of
      an embryonic ventral mesencephalic (VM) dopamine (DA) neuron graft on levodopa
      (LD)-induced dyskinetic movements in unilaterally 6-hydroxydopamine-lesioned
      rats. Rats were administered LD (levodopa-carbidopa, 50:5 mg/kg) twice daily for
      6 weeks after either a sham graft or VM DA graft. Although a single solid graft
      of embryonic DA neurons can prevent progression of some lesioned-induced
      behavioral abnormalities such as LD-induced rotation and dystonia, it
      significantly increases hyperkinetic movements of the contralateral forelimb.
      This differential effect of grafted neurons on abnormal behavioral profiles is
      reminiscent of that reported in grafted patients with PD. Data from this study
      illustrate important similarities between this model of parkinsonism and PD in
      human patients that make it suitable for initial preclinical investigations into
      possible mechanisms underlying postgraft aggravation of dyskinetic movements.

PMID- 14673881
TI  - Standardized training tools for the UPDRS activities of daily living scale: newly
      available teaching program.
AB  - The Unified Parkinson's Disease Rating Scale (UPDRS) is the most widely used
      scale for evaluation of clinical impairment in PD. Whereas the motor section has
      been studied intensively for clinimetric properties and has an associated
      training tape, the Activities of Daily Living (ADL) section has been studied less
      rigorously. In preparation for a multicenter study that planned to use the UPDRS
      ADL score as an outcome, the authors reviewed the UPDRS ADL scale and designed a
      teaching program to provide a uniform technique for data acquisition without
      changing any wording of the primary scale. The teaching program is composed of
      four components: overall guidelines, clarifying points, recommended strategies,
      and a teaching videotape. The videotape shows examples of interviewers assessing
      each ADL item with patients of different disability levels and provides a
      complete ADL assessment of a single patient. Systematic training and utilization
      of this teaching program offer the potential for more uniformity in results of
      ADL assessments conducted in clinical practice and multicenter, international
      studies of PD. The written materials and videotape belong to the Movement
      Disorder Society and are available by contacting the MDS central office.

PMID- 14673882
TI  - Sweating dysfunction in Parkinson's disease.
AB  - We sought to determine the prevalence and nature of sweating disturbances in
      patients with Parkinson's disease (PD), and investigated their correlation with
      other clinical features and with Quality of Life (QoL) measures. A questionnaire
      on symptoms and consequences of sweating dysfunction was completed by 77
      consecutive outpatients, from three movement disorder clinics, and 40 controls.
      QoL was assessed using the disease-specific Parkinson's Disease Questionnaire
      (PDQ)-39 and generic EuroQoL (EQ)-5D rating scales. Patients also underwent a
      clinical examination, including assessment with the Unified Parkinson's Disease
      Rating Scale and the Hoehn and Yahr staging system. Sweating disturbances, either
      hypohidrosis or in particular, hyperhidrosis, were reported by 64% of patients
      and by 12.5% of controls (P < 0.005) and were often localised or asymmetric.
      Complaints of sweating disturbances were not correlated with disease severity,
      but did correlate with other symptoms of autonomic dysfunction. Sweating problems
      occurred predominantly in off periods and in on periods with dyskinesias.
      Sweating disturbances were not correlated with overall QoL scores, but we did
      observe a significant correlation with the pain dimension of the PDQ-39 and the
      visual analogue scale of the EQ-5D. Furthermore, many patients reported physical,
      social, and emotional impairment due to sweating. Sweating disturbances are
      common and distressing symptoms of PD that are related mainly to autonomic
      dysfunction, off periods, and dyskinesias.

PMID- 14673883
TI  - Health-related quality of life in patients with progressive supranuclear palsy.
AB  - We assessed health-related quality of life (QoL) of patients with progressive
      supranuclear palsy (PSP), identified the most important QoL issues in patients
      with this disorder, and assessed the usefulness of existing QoL measures in
      patients with PSP. Twenty-seven patients in all stages of PSP and their carers
      underwent a semistructured in-depth interview on the impact of PSP and a
      neurological examination. They were also asked to complete existing measures of
      QoL and depression. An item-pool of issues relevant to QoL of patients with PSP
      was created from the patient and carer interviews. Carers and patients largely
      agreed on issues relevant for patients' QoL but more carers than patients
      considered symptoms of frontal lobe dysfunction as problematic for the patients.
      There was no association of QoL with age and gender, as assessed in interviews
      and on two QoL instruments. QoL deteriorated with increasing disease duration and
      severity and greater cognitive impairment and was associated with worse
      depression scores. While the generic SF-36 was not found to be useful to assess
      QoL in PSP, feasibility and validity for the PDQ-39 and the EQ-5D were acceptable
      in this study. However, additional issues relevant to patients with PSP that were
      not addressed in these instruments included visual disturbances, dysarthria,
      dysphagia, muddled thinking, confusion, and apathy. The generic EQ-5D and the
      Parkinson's disease-specific PDQ-39 are useful instruments to assess QoL in
      patients with PSP. However, they lack questions on important aspects of QoL in
      PSP that were reported by patients and carers in semistructured interviews. The
      item pool created in these interviews provides the basis for the development of
      disease-specific QoL instruments for patients with PSP.

PMID- 14673884
TI  - Cognitive executive function in dystonia.
AB  - Dystonia is a movement disorder considered to result from basal ganglia
      dysfunction. The aim of this study was to investigate the functional significance
      of frontal hyperactivity demonstrated in dystonia in imaging studies by examining
      executive function and working memory, in which the prefrontal cortex is known to
      be involved. We assessed 10 patients with idiopathic dystonia and 12 age- and IQ
      matched normal controls. All subjects completed tests of first letter, category,
      and alternating category word fluency, the Wisconsin Card Sorting Test, the
      Stroop Colour Word Naming Test, the Missing Digit Test of working memory, a test
      of random number generation, a test requiring generation of self-ordered random
      number sequences, the Paced Serial Addition Test, a test of conditional
      associative learning, and finger tapping and peg insertion under unimanual,
      bimanual, and dual task conditions. The patients with dystonia did not differ
      significantly from controls on any measures of executive function or working
      memory used other than category word fluency and the extent of decline in tapping
      with one hand under dual task conditions when simultaneously inserting pegs with
      the other hand. For this small sample, the results suggest that unlike other
      movement disorders associated with fronto-striatal dysfunction such as
      Parkinson's disease or Huntington's disease, dystonia was not associated with
      deficits on the tests of executive function or working memory used. A more
      detailed investigation of cognitive function in a larger sample of patients is
      required.

PMID- 14673885
TI  - Posttraumatic painful torticollis.
AB  - The development of abnormal posturing of the neck or shoulder after local injury
      has been termed posttraumatic cervical dystonia (PTCD). Certain features seem to
      distinguish a unique subgroup of patients with this disorder from those with
      features more akin to typical idiopathic cervical dystonia, such as onset and
      maximum disability that occurs very quickly after injury, severe pain and a fixed
      abnormal posture. In an attempt to clarify the nature of this syndrome further,
      we evaluated 16 such patients (8 men, 8 women). Motor vehicle accident and work
      related injuries were common precipitants, with posturing usually developing
      shortly after trauma, and little progression occurring after the first week. A
      characteristic, painful, fixed head tilt and shoulder elevation were present in
      all but one patient, who had a painless elevated shoulder and painful
      contralateral shoulder depression, as well as nondermatomal sensory loss in 14
      patients. Additional abnormalities included dystonic posturing in a limb (2
      patients) or jaw (1 patient), limb tremor (3 patients) and "give-way" limb
      weakness (8 patients). The tremor and the jaw dystonia demonstrated features
      suggestive of a psychogenic movement disorder, most commonly distractibility.
      Litigation or compensation was present in all 16 patients. Intravenous sodium
      amytal improved the posture, pain or both in 13 of 13 patients; in 7 of 13 the
      sensory deficit either markedly improved or normalized. General anesthesia
      demonstrated full range of motion in all 5 patients assessed. Psychological
      evaluations suggested that psychological conflict, stress, or both were being
      expressed via somatic channels in 11 of 12 tested patients. Our results suggest
      an important role of psychological factors in the etiology or maintenance of
      abnormal posture, pain and associated disability of these patients. The role of
      central factors triggered in psychologically vulnerable individuals after
      physical trauma is discussed. We propose that the disorder be referred to as
      "posttraumatic painful torticollis" rather than characterize it as a form of
      dystonia until further information on its pathogenesis is forthcoming.

PMID- 14673886
TI  - Dystonia in AIDS: report of four cases.
AB  - Dystonia is a rare complication of acquired immune deficiency syndrome (AIDS). We
      report four such cases related to three different causes. Cases 1 and 2 both
      developed dystonia secondary to biopsy-proven progressive multifocal
      leukoencephalopathy. One had left arm dystonia, whereas the other had bilateral
      upper limb dystonia. One patient had associated akinesia and rigidity. Imaging
      demonstrated frontal and/or parietal white matter lesions but no basal ganglia
      abnormalities. Case 3 developed hemidystonia and cervical dystonia from biopsy
      proven toxoplasmosis with a lesion in the thalamus. Case 4 suffered from AIDS
      dementia complex and developed cervical dystonia while taking risperidone
      therapy. We also review previously reported cases of dystonia in AIDS patients
      with the same causes and discuss the issue of increased vulnerability of the
      basal ganglia to HIV infection which, in turn, leads to increased sensitivity to
      neuroleptics. When dystonia is seen in AIDS patients, its pattern may be a clue
      to the ultimate cause.

PMID- 14673887
TI  - Deficits induced by quinolinic acid lesion to the striatum in a position
      discrimination and reversal task are ameliorated by permanent and temporary
      lesion to the globus pallidus: a potential novel treatment in a rat model of
      Huntington's disease.
AB  - Symptoms in the early stages of Huntington's disease (HD) are assumed to reflect
      basal ganglia circuit dysfunction secondary to degeneration of striatal
      projections to the external segment of the globus pallidus (GPe). The hypothesis
      that GPe lesion would ameliorate HD symptoms by "normalizing" the circuit's
      functioning was tested in a rat model of this disease. The performance of rats
      sustaining quinolinic acid lesion to the striatum (a rat model of HD) in a
      position discrimination and reversal task was compared with the performance of
      rats sustaining in addition a bilateral excitotoxic lesion to the globus pallidus
      (GP) carried out simultaneously with the striatal lesion (Experiment 1) or 1
      month after the striatal lesion (Experiment 2), as well as a unilateral temporary
      lesion of the GP (Experiment 3). The striatal lesion-induced deficit in the task
      was effectively reversed by a bilateral excitotoxic GP lesion carried out
      simultaneously or 1 month after the striatal lesion, as well as by a temporary
      unilateral GP inactivation. Given that a similar dysfunction of basal ganglia
      circuitry is thought to subserve the behavioral alterations seen in quinolinic
      acid lesioned rats and some of the symptoms in HD, these results raise the
      possibility that lesion or inactivation of the GPe may alleviate some of HD
      symptoms.

PMID- 14673888
TI  - Deep brain stimulation for Parkinson's disease dissociates mood and motor
      circuits: a functional MRI case study.
AB  - Behavioral disturbances have been reported with subthalamic (STN) deep brain
      stimulation (DBS) treatment in Parkinson's disease (PD). We report correlative
      functional imaging (fMRI) of mood and motor responses induced by successive right
      and left DBS. A 36-year-old woman with medically refractory PD and a history of
      clinically remitted depression underwent uncomplicated implantation of bilateral
      STN DBS. High-frequency stimulation of the left electrode improved motor
      symptoms. Unexpectedly, right DBS alone elicited several reproducible episodes of
      acute depressive dysphoria. Structural and functional magnetic resonance imaging
      (fMRI) imaging was carried out with sequential individual electrode stimulation.
      The electrode on the left was within the inferior STN, whereas the right
      electrode was marginally superior and lateral to the intended STN target within
      the Fields of Forel/zona incerta. fMRI image analysis (Analysis of Functional
      NeuroImages, AFNI) contrasting OFF versus ON stimulation identified significant
      lateralized blood oxygen level-dependent (BOLD) signal changes with DBS (P <
      0.001). Left DBS primarily showed changes in motor regions: increases in premotor
      and motor cortex, ventrolateral thalamus, putamen, and cerebellum as well as
      decreases in sensorimotor/supplementary motor cortex. Right DBS showed similar
      but less extensive change in motor regions. More prominent were the unique
      increases in superior prefrontal cortex, anterior cingulate (Brodmann's area [BA]
      24), anterior thalamus, caudate, and brainstem, and marked widespread decreases
      in medial prefrontal cortex (BA 9/10). The mood disturbance resolved
      spontaneously in 4 weeks despite identical stimulation parameters. Transient
      depressive mood induced by subcortical DBS stimulation was correlated with
      changes in mesolimbic cortical structures. This case provides new evidence
      supporting cortical segregation of motor and nonmotor cortico-basal ganglionic
      systems that may converge in close proximity at the level of the STN and the
      adjacent white matter tracts (Fields of Forel/zona incerta).

PMID- 14673889
TI  - Parkinson's disease, subthalamic stimulation, and selection of candidates: a
      pathological study.
AB  - We report on a patient with Parkinson's disease (PD) who was moderately improved
      by stimulation of the subthalamic nucleus (STN) and died 2 years after electrode
      implantation. After neurosurgery, symptoms that had responded to levodopa
      treatment preoperatively continued to improve. Postural instability, dysarthria,
      and cognitive impairment continued to worsen, despite STN stimulation and
      levodopa treatment. Postmortem examination of the brain confirmed the diagnosis
      of PD and showed that the electrodes had been correctly positioned within the
      STN. The failure of STN stimulation in this patient confirms the importance of
      screening and excluding patients from surgery with evolving parkinsonian axial
      symptoms or cognitive impairment.

PMID- 14673890
TI  - REM behavior disorder and excessive daytime somnolence in Machado-Joseph disease
      (SCA-3).
AB  - We reported previously that behavior suggestive of rapid eye movement sleep
      behavior disorder (RBD) was markedly increased in a small population of SCA-3
      patients. We, therefore, asked patients and nonpatient attendees at an SCA-3
      annual clinic to complete a questionnaire soliciting RBD-like behavior. Our
      results support the previous observation that RBD-like behaviors are
      significantly increased in SCA-3.

PMID- 14673891
TI  - Auditory startle response in cervical dystonia.
AB  - The excitability of brainstem neurons is abnormally enhanced in patients with
      cervical dystonia (CD), but the extend of such abnormality is not known. We
      examined whether patients with CD showed abnormalities in the auditory startle
      response (ASR), a brainstem reflex elicited by an unexpected loud stimulus.
      Thirteen patients with CD were investigated 3 months after botulinum toxin
      treatment. Thirteen healthy volunteers served as controls. ASRs were elicited by
      binaural high-intensity auditory stimuli. Reflex electromyographic (EMG) activity
      was recorded simultaneously with surface electrodes bilaterally from masseter,
      orbicularis oculi, sternocleidomastoid, and biceps brachii muscles. We found that
      ASR onset latencies were similar for patients and controls. CD patients had
      significantly lower ASR probabilities than controls (P = 0.007). ASR area under
      the curve was significantly smaller in CD patients (P = 0.017). Similar to
      controls, patients showed a significant habituation of ASR (P < 0.001, each);
      however, CD patients showed a prolonged tonic or phasic EMG activity after the
      initial ASR that was not observed in controls. Normal latencies and recruitment
      pattern indicate a preserved organization of intrinsic neural pathways mediating
      ASR in CD. Reduced ASR probability and magnitude as well as prolonged EMG
      activity after the proper startle response corroborate and extend previous
      findings on brainstem dysfunction in CD.

PMID- 14673892
TI  - Phenotypic features of Huntington's disease-like 2.
AB  - Huntington's disease-like 2 is an autosomal dominantly inherited disorder due to
      an expansion of trinucleotide repeats. It resembles classic Huntington's disease
      in clinical phenotype, inheritance pattern, and neuropathological features. We
      highlight the clinical features of this disorder, including chorea, dystonia,
      parkinsonism, and cognitive deficits.

PMID- 14673893
TI  - Premonitory sensory phenomenon in Tourette's syndrome.
AB  - We administered a questionnaire designed to probe for premonitory sensations
      associated with motor tics to 50 patients with Tourette's syndrome (TS).
      Premonitory sensations were reported by 46 (92%) patients, and the most common
      sensation was an urge to move and an impulse to tic ("had to do it").
      Intensification of premonitory sensations, if prevented from performing a motor
      tic, was reported also in 37 patients (74%), 36 patients (72%) reported relief of
      premonitory sensations after performing the tic, and 27 of 40 (68%) described a
      motor tic as a voluntary motor response to an involuntary sensation, rather than
      a completely involuntary movement. The "just right" sensation correlated with the
      presence of co-morbid obsessive-compulsive disorder. We conclude that premonitory
      sensations are an important aspect of motor tics and some patients perceive motor
      tics as a voluntary movement in response to an involuntary sensation.

PMID- 14673894
TI  - Rhythmic cortical myoclonus in a case of HIV-related encephalopathy.
AB  - We describe a 66-year-old, HIV-seropositive patient presenting with ataxia and
      upper limb rhythmic myoclonus activated by postural maintenance. Electromyograph
      (EMG) recordings of the forearm muscles showed 50-msec bursts, with a frequency
      of 10 Hz, concurring with frontocentral electroencephalograph (EEG) rhythmic
      activity. Autoregressive spectral analysis applied to the EEG-EMG traces made it
      possible to detect significant coherence between the rhythmic EEG discharges and
      EMG bursts. The amplitude of the middle-latency somatosensory evoked potentials
      was increased. Long-latency reflexes were enhanced. On the basis of the
      electrophysiological findings, the movement disorder should be considered a
      rhythmic variant of cortical myoclonus. In our patient, HIV infection may have
      caused a dysfunction in the central nervous system pathways involving the
      cerebellum and sensorimotor cortex, similar to that occurring in genetically
      determined conditions characterised by cortical myoclonus.

PMID- 14673895
TI  - Magnetic resonance spectroscopy of cerebral cortex is normal in hereditary
      hyperekplexia due to mutations in the GLRA1 gene.
AB  - Excessive startling and stiffness in hereditary hyperekplexia has been attributed
      to lack of inhibition at either the cortical or brainstem level. Six patients
      with hereditary hyperekplexia (HH) and a confirmed mutation in the gene encoding
      the alpha(1) subunit of the glycine receptor (GLRA1) underwent single voxel (1)H
      magnetic resonance spectroscopy (MRS) of the brainstem and an area of frontal
      cortex and white matter using a method that allows absolute quantification of
      metabolites. The results of MRS were within normal limits, although there was a
      tendency for the neuronal marker N-acetyl aspartate to be reduced in the
      brainstem of patients compared with that in controls. Thus, we found no evidence
      to support a deficit in the cerebral cortex in patients with hereditary
      hyperekplexia due to mutations in the GLRA1 gene.

PMID- 14673896
TI  - Subtraction brain SPECT imaging in a patient with gait ignition failure.
AB  - The precise anatomical location and pathophysiology of gait ignition failure
      (GIF) is poorly understood. We investigated the cerebral perfusion patterns using
      subtraction brain single photon emission computed tomography (SPECT) in a patient
      with GIF. Subtraction brain SPECT imaging revealed an increased activity in the
      region of right ventrolateral midbrain and ventral medulla.

PMID- 14673897
TI  - Paroxysmal exercise-induced dystonia as a presenting feature of young-onset
      Parkinson's disease.
AB  - Paroxysmal exercise-induced dystonia (PED) is a rare, typically idiopathic
      familial condition, although sporadic and secondary cases have been reported. We
      present 2 cases where PED was the presenting feature of young-onset idiopathic
      Parkinson's disease (PD), preceding the onset of parkinsonian symptoms by 1.5 and
      5 years, respectively. Initially, the dystonic symptoms occurred after prolonged
      exercise and were unilateral, affecting the foot in both patients. Over time,
      symptoms occurred with minimal exercise. We conclude that PED can rarely be the
      first and only feature of PD.

PMID- 14673898
TI  - Dystonia in a patient with ring chromosome 21.
AB  - Dystonia associated with chromosomal abnormalities is typically attributed to
      chromosomal deletions. We describe a patient with ring chromosome 21, with
      karyotype 46XX,r(21)(p11.2q22.3); 46,XX,dic r(21)(p11.2q22.3); 45, XX, -21, who
      developed childhood onset cervical dystonia.

PMID- 14673899
TI  - Pure cerebello-olivary degeneration of Marie, Foix, and Alajouanine presenting
      with progressive cerebellar ataxia, cognitive decline, and chorea.
AB  - Parenchymatous cerebellar cortical atrophy (CCA) usually presents with a "pure"
      cerebellar ataxia. We describe a patient with a sporadic, late-onset progressive
      cerebellar ataxia plus cognitive decline and chorea who had CCA at post mortem.
      We discuss this unique case in the current context of classification of
      idiopathic cerebellar ataxia.

PMID- 14673900
TI  - Striatal encephalitis after varicella zoster infection complicated by Tourettism.
AB  - We describe a case of encephalitis after primary varicella zoster infection with
      localised basal ganglia imaging abnormalities. The patient subsequently developed
      a chronic tic disorder with attention deficit disorder. This case furthers the
      proposed association between Tourettism and the basal ganglia.

PMID- 14673901
TI  - Paraneoplastic movement disorder in a patient with non-Hodgkin's lymphoma and
      CRMP-5 autoantibody.
AB  - The paraneoplastic autoantibody, collapsin response-mediator protein (CRMP)-5
      immunoglobulin G (IgG), is specific for neuronal cytoplasmic CRMP-5, and is
      usually associated with small-cell lung carcinoma or thymoma. We report on
      details of a movement disorder that followed anti-B-cell therapy in a patient
      with lymphoma, and was accompanied by CRMP-5 IgG.

PMID- 14673902
TI  - Epilepsia partialis continua in progressive multifocal leukoencephalopathy: a
      motor cortex isolation syndrome.
AB  - We describe the clinical and neuropathological features in a patient aged 45
      years with progressive multifocal leukoencephalopathy with epilepsia partialis
      continua. The motor cortex and basal ganglia were preserved. Our findings lend
      support to the notion of isolation of the motor cortex as the cause of this
      particular type of focal status epilepticus.

PMID- 14673903
TI  - Atypical propriospinal myoclonus with possible relationship to alpha interferon
      therapy.
AB  - We report on a man who received interferon-alpha 2a therapy for kidney cancer and
      who subsequently developed propriospinal myoclonus. The myoclonus was noted at
      rest and during movement. The jerks were reinforced by cutaneous stimuli and
      tendon taps and spread to the spinal cord via polysynaptic propriospinal
      pathways. Cerebrospinal fluid analysis, spinal cord magnetic resonance imaging,
      electroencephalogram with back-averaging, and somatosensory-evoked potentials
      were normal. No antineuronal antibodies were found. Although the mechanism of
      interferon neurotoxicity remains unclear, the possible responsibility of
      interferon was considered, as no focal lesion or paraneoplastic pathology were
      disclosed.

PMID- 14673904
TI  - Sleep attacks may not be a side effect of dopaminergic medication.

PMID- 14673908
TI  - Synthetic routes towards enantiomerically pure beta-amino acids.

PMID- 14673909
TI  - Functional hybrid devices of proteins and inorganic nanoparticles.

PMID- 14673910
TI  - Domains and rafts in lipid membranes.
AB  - "It takes a membrane to make sense out of disorder in biology. You have to be
      able to catch energy and hold it, storing precisely the needed amount and
      releasing it in measured shares". So wrote Lewis Thomas in The Lives of Cells.
      Domains and rafts are shown in the present Review to play an important role in
      this amazing behavior of lipid membranes. Topics touched upon include the
      experimental detection of domains, their composition, domain induction,
      properties of rafts (a special form of domain), and the relationship of rafts to
      human diseases. Lipids, polymers, and proteins can contribute to this type of
      micro- and nanostructuring within membranes, thus imposing a new structural
      hierarchy on top of the classical bilayer membrane. The purpose of this Review is
      to develop an appreciation for the multiple organizational levels in self
      assembling systems.

PMID- 14673911
TI  - Staudinger ligation: a new immobilization strategy for the preparation of small
      molecule arrays.

PMID- 14673912
TI  - Electric current through a molecular rod-relevance of the position of the anchor
      groups.

PMID- 14673913
TI  - (-)-Daucic acid: revision of configuration, synthesis, and biosynthetic
      implications.

PMID- 14673914
TI  - Binary tellurium(IV) azides: Te(N3)4 and [Te(N3)5]-.

PMID- 14673915
TI  - Polyazide chemistry: preparation and characterization of Te(N3)4 and
      [P(C6H5)4]2[Te(N3)6] and evidence for [N(CH3)4][Te(N3)5].

PMID- 14673916
TI  - The usefulness of time-dependent density functional theory to describe the
      electronic spectra of ti-containing catalysts.

PMID- 14673917
TI  - Intramolecular organocatalytic [3+2] dipolar cycloaddition: stereospecific
      cycloaddition and the total synthesis of (+/-)-hirsutene.

PMID- 14673918
TI  - Continuous glucose sensing with a fluorescent thin-film hydrogel.

PMID- 14673919
TI  - Three/four/five-component diastereoselective cyclization of Fischer carbene
      complexes, lithium enolates, and allylmagnesium bromide.

PMID- 14673920
TI  - Packing motifs in porphyrazine macrocycles carrying peripherally annulated
      thiadiazole rings: crystal growths of metal-free and cobalt tetrakis(1,2,5
      thiadiazole)porphyrazines.

PMID- 14673922
TI  - Practical asymmetric synthesis of vicinal diamines through the catalytic highly
      enantioselective alkylation of glycine amide derivatives.

PMID- 14673921
TI  - Palladium-catalyzed equilibrium addition of acidic OH groups across dienes.

PMID- 14673923
TI  - Asymmetric addition of aryl boron reagents to enones with rhodium dicyclophane
      imidazolium carbene catalysis.

PMID- 14673925
TI  - Breaking down barriers: the liaison between sigmatropic shifts, electrocyclic
      reactions, and three-center cations.

PMID- 14673924
TI  - Sulfoxide covalent catalysis: application to glycosidic bond formation.

PMID- 14673926
TI  - Synthesis and characterization of oligonucleotides containing the c4'-oxidized
      abasic site produced by bleomycin and other DNA damaging agents.

PMID- 14673927
TI  - Entropy-driven translational isomerism: a tristable molecular shuttle.

PMID- 14673928
TI  - Towards the rational design of magnetic resonance imaging contrast agents:
      isolation of the two coordination isomers of lanthanide DOTA-type complexes.

PMID- 14673929
TI  - Why does TNA cross-pair more strongly with RNA than with DNA? an answer from X
      ray analysis.

PMID- 14673930
TI  - Ultrafast dynamics in DNA-mediated electron transfer: base gating and the role of
      temperature.

PMID- 14673933
TI  - Estimating the incidence of subclinical infections with Legionella Pneumonia
      using data augmentation: analysis of an outbreak in The Netherlands.
AB  - Infections with Legionella bacteria can cause a potentially lethal form of
      pneumonia known as legionnaires' disease. In 1999 a major outbreak, causing 31
      deaths, occurred among visitors and exhibitors of a consumer fair in The
      Netherlands. The epidemiology of subclinical infections is largely unknown, as
      there is no reliable method to diagnose such infections. To explore the incidence
      of subclinical infections, IgG and IgM antibody levels among exhibitors were
      compared to those among a representative sample of the Dutch population. As
      exhibitors were assumed to comprise both infected and uninfected individuals,
      their antibody levels were modelled as a mixture distribution. As infected
      individuals are expected to cluster around a point source, the spatial aspect of
      the spread of infections was taken into account. To estimate the distribution of
      antibody levels among infected individuals and to impute infection status among
      exhibitors, data augmentation was used. Subclinical infection appeared to be very
      common and its frequency declined with the distance from the putative source of
      the outbreak.

PMID- 14673934
TI  - Intervention effects in observational survival studies with an application in
      total hip replacements.
AB  - Time to revision is a common and clinically relevant endpoint for studies of
      patients with total hip replacement. Because failures occur rarely within the
      first years after replacement, new surgical techniques and materials are often
      implemented without evidence of their effectiveness from randomized trials.
      Observational data may be available but this relies on the use of historical
      controls which has been heavily criticized. Instead the use of changepoint
      methods has been suggested to detect changes caused by successfully implemented
      interventions. In the setting of a proportional hazards model we develop a semi
      parametric changepoint method to detect changes in baseline hazard. The procedure
      is motivated by and applied to a clinical study in patients with total hip
      replacements, where the effect of a new cement type is of interest. Power
      properties of the proposed method are investigated.

PMID- 14673935
TI  - The analysis of the influence of birth order and other factors in multiple birth
      data.
AB  - We compare three methods which can be used to analyse the influence of birth
      order and other factors on health outcomes in multiple birth data. We consider
      marginal models based on generalized estimating equations (GEE) and two kinds of
      conditional models; conditional logistic regression (CLR) and mixed effects
      models (MEM). Although the models may be written similarly, there are differences
      in both the interpretation and the numerical values assigned to the parameters.
      Our main conclusion is that GEE and MEM are preferable to CLR since they provide
      more flexibility in dealing with missing values and covariates. The choice
      between GEE and MEM is less obvious and depends on the data, the parameter of
      interest and statistical power.

PMID- 14673936
TI  - The analysis of asthma control under a Markov assumption with use of covariates.
AB  - In studies of disease states and their relation to evolution, data on the state
      are usually obtained at in frequent time points during follow-up. Moreover in
      many applications, there are measured covariates on each individual under study
      and interest centres on the relationship between these covariates and the disease
      evolution. We developed a continuous-time Markov model with use of time-dependent
      covariates and a Markov model with piecewise constant intensities to model asthma
      evolution. Methods to estimate the effect of covariates on transition
      intensities, to test the assumption of time homogeneity and to assess goodness-of
      fit are proposed. We apply these methods to asthma control. We consider a three
      state model and we discuss in detail the analysis of asthma control evolution.

PMID- 14673937
TI  - Construction of a global score quantifying allelic imbalance among biallelic SIDP
      markers in bladder cancer.
AB  - The purpose of this paper is the construction of an adapted statistical test for
      urinary detection of bladder cancer based on the assessment of allelic imbalance
      using biallelic Short Insertion/Deletion Polymorphism DNA markers. This test is
      based on the comparison of several of these markers, analysed from urinary DNA,
      to the distribution of their analogues in blood, which is taken as reference. A
      reproductibility study is first performed in blood in order to make a selection
      among the 23 available markers and 18 are retained. A global score based on the
      chi2 distribution is then built to test for allelic imbalance among all
      informative markers for each patient. It avoids the count of DNA abnormalities
      marker by marker and allows to take into account the degree of abnormality of
      each marker. That method is preliminarily evaluated on a sample of 53 patients
      and 27 controls. The estimated specificity (96.3%) on that reduced sample is
      satisfactory, whereas sensitivity (60.4%) could be improved by an augmentation of
      the number of tested markers. Several issues regarding the validity of the method
      are discussed.

PMID- 14673938
TI  - Evaluation of Cox's model and logistic regression for matched case-control data
      with time-dependent covariates: a simulation study.
AB  - Case-control studies are typically analysed using the conventional logistic
      model, which does not directly account for changes in the covariate values over
      time. Yet, many exposures may vary over time. The most natural alternative to
      handle such exposures would be to use the Cox model with time-dependent
      covariates. However, its application to case-control data opens the question of
      how to manipulate the risk sets. Through a simulation study, we investigate how
      the accuracy of the estimates of Cox's model depends on the operational
      definition of risk sets and/or on some aspects of the time-varying exposure. We
      also assess the estimates obtained from conventional logistic regression. The
      lifetime experience of a hypothetical population is first generated, and a
      matched case-control study is then simulated from this population. We control the
      frequency, the age at initiation, and the total duration of exposure, as well as
      the strengths of their effects. All models considered include a fixed-in-time
      covariate and one or two time-dependent covariate(s): the indicator of current
      exposure and/or the exposure duration. Simulation results show that none of the
      models always performs well. The discrepancies between the odds ratios yielded by
      logistic regression and the 'true' hazard ratio depend on both the type of the
      covariate and the strength of its effect. In addition, it seems that logistic
      regression has difficulty separating the effects of inter-correlated time
      dependent covariates. By contrast, each of the two versions of Cox's model
      systematically induces either a serious under-estimation or a moderate over
      estimation bias. The magnitude of the latter bias is proportional to the true
      effect, suggesting that an improved manipulation of the risk sets may eliminate,
      or at least reduce, the bias.

PMID- 14673939
TI  - Comparison of case-cohort estimators based on data on premature death of adult
      adoptees.
AB  - A case-cohort sample of adoptees was collected to investigate genetic and
      environmental influences on premature death, which motivated us to supplement
      existing simulation results to explore the performance of various estimators
      proposed for case-cohort samples of survival data. We studied six regression
      coefficients estimators, which differ with regard to the weighting scheme used in
      a pseudo-likelihood function, and two different estimators of their variances.
      Compared to earlier simulation studies, we changed the following conditions: type
      of explanatory variable, the distribution of lifetimes, and the percentage of
      deaths in the full cohort. The latter condition affected the performance of the
      estimated variances of the regression coefficients, where we found a systematic
      bias of the estimator, proposed by Self and Prentice, dependent on the
      percentages of deaths. This dependence of percentages of death was different for
      different sizes of case-cohort studies. A robust variance estimator showed a
      better overall performance. The estimators of regression coefficients compared
      did not differ much, the estimators proposed by Kalbfleisch and Lawless and by
      Prentice performing very well. Results of the case-cohort data of adoptees were
      not in conflict with earlier findings of a moderate genetic influence on
      premature death in adulthood.

PMID- 14673940
TI  - Non-parametric bootstrap confidence intervals for the intraclass correlation
      coefficient.
AB  - The intraclass correlation coefficient rho plays a key role in the design of
      cluster randomized trials. Estimates of rho obtained from previous cluster trials
      and used to inform sample size calculation in planned trials may be imprecise due
      to the typically small numbers of clusters in such studies. It may be useful to
      quantify this imprecision. This study used simulation to compare different
      methods for assigning bootstrap confidence intervals to rho for continuous
      outcomes from a balanced design. Data were simulated for combinations of numbers
      of clusters (10, 30, 50), intraclass correlation coefficients (0.001, 0.01, 0.05,
      0.3) and outcome distributions (normal, non-normal continuous). The basic,
      bootstrap-t, percentile, bias corrected and bias corrected accelerated bootstrap
      intervals were compared with new methods using the basic and bootstrap-t
      intervals applied to a variance stabilizing transformation of rho. The standard
      bootstrap methods provided coverage levels for 95 per cent intervals that were
      markedly lower than the nominal level for data sets with only 10 clusters, and
      only provided close to 95 per cent coverage when there were 50 clusters.
      Application of the bootstrap-t method to the variance stabilizing transformation
      of rho improved upon the performance of the standard bootstrap methods, providing
      close to nominal coverage.

PMID- 14673941
TI  - Proper metrics for clinical trials: transformations and other procedures to
      remove non-normality effects.
AB  - A simulation study was performed to study the effects of non-normality and to
      examine procedures to ameliorate possible loss of power when data are incorrectly
      assumed to be normally distributed. It was found that only distributions with
      high asymmetry or heavy tails seriously affect the t-test. The Box-Cox likelihood
      ratio test appears to have some advantages over the others, but this must be
      offset by the greater complexity in making the results understandable to non
      statisticians. The variability in outcomes with the different procedures
      demonstrates the importance of specifying such procedures a priori.

PMID- 14673942
TI  - Sample size re-estimation in group-sequential response-adaptive clinical trials.
AB  - In clinical trials where the variances of the response variables are unknown, in
      accurate estimates of these can affect the type II error rate considerably. More
      accurate estimates of the variances may be obtained by taking a look at the data
      available part way through the trial and re-calculating the required sample size
      based on these new estimates. The main impetus for sample size re-estimation came
      from a two-stage procedure developed by Stein in 1945 and the literature is now
      replete with variations on this approach. In this paper, existing sample size re
      estimation methods for both fixed sample and sequential clinical trial models
      will be reviewed. These will then be extended for use in group-sequential
      response-adaptive designs. In particular, a test for a recently developed group
      sequential response-adaptive design, which compares two treatments with immediate
      normally distributed responses and unknown variances, is presented based on a
      modified version of Stein's test. The principal modifications involve updating
      the required sample size at each interim analysis and calculating the test
      statistic based on the current estimates of the variances. Hence, all the
      available information is used at each stage. Simulation is used to assess to what
      extent the updating of the required sample size at each interim analysis in the
      new test helps to attain the nominal error rates. The test is compared to
      modified versions of a simple test and a Stein-type group sequential t-test
      studied in the recent literature. These tests calculate the required sample sizes
      based on less accurate estimates of the variances. The type I error rate is close
      to the nominal value and the power is more accurately maintained in the new test.

PMID- 14673943
TI  - Power comparison of two-sided exact tests for association in 2 x 2 contingency
      tables using standard, mid p and randomized test versions.
AB  - Exact Pearson's chi square, likelihood ratio (LR), and Fisher's tests are
      obtained from the conditional distribution of its test statistic, given the row
      and column sums of the contingency table. The power and obtained significance
      level of the standard, mid p, and randomized versions of these tests are compared
      for two-sided tests in 2 x 2 tables, using binomial and multinomial sampling. The
      mid p type I error probabilities seldom exceed the nominal significance level.
      The mid p and randomized test versions have approximately the same power, and
      higher power than the standard test version. The power of the Pearson's chi
      square, LR and Fisher's test differ, and they differ in approximately the same
      way for standard, mid p and randomized test versions for any given set of
      parameters. There is no general ranking between the three tests. In many cases,
      Pearson's chi square and Fisher's tests have almost equal power, and higher power
      than LR. In a few cases, perhaps characterized by poorly balanced designs, LR
      performs best. Fisher's test seems to be slightly more robust even if the design
      is poor.

PMID- 14673944
TI  - The heritability of cause-specific mortality: a correlated gamma-frailty model
      applied to mortality due to respiratory diseases in Danish twins born 1870-1930.
AB  - The genetic influence on susceptibility to diseases of the respiratory system and
      all-cause mortality was studied using data for identical (MZ) and fraternal (DZ)
      twins. Data from the Danish Twin Register include 1344 MZ and 2411 DZ male twin
      pairs and 1470 MZ and 2730 DZ female twin pairs born between 1870 and 1930, where
      both individuals were alive on 1 011943. We used the correlated gamma-frailty
      model. Proportions of variance in frailty attributable to genetic and
      environmental factors were assessed using the structural equation model approach.
      For all-cause mortality the correlation coefficients of frailty for MZ twins tend
      to be higher than for DZ twins. For mortality with respect to respiratory
      diseases this effect was only seen in females, whereas males showed the opposite
      effect. Five standard biometric models are fitted to the data to evaluate the
      magnitude and nature of genetic and environmental factors on mortality. Using the
      best fitting biometric model heritability for cause of death was found to be 0.58
      (0.07) for all-cause mortality (AE-model) and zero for diseases of the
      respiratory system for males. Heritability was 0.63 (0.11) for all-cause
      mortality (DE-model) and 0.18 (0.09) for diseases of the respiratory system (DE
      model) for females. The analysis confirms the presence of a strong genetic
      influence on individual frailty associated with all-cause mortality. For
      respiratory diseases, no genetic influence was found in males and only weak
      genetic influence in females. The nature of genetic influences on frailty with
      respect to all-cause mortality is probably additive in males and dominant in
      females, whereas for frailty with respect to deaths caused by respiratory
      diseases in females, there are genetic factors present which are caused by
      dominance. Environmental influences are non-shared with exception of frailty with
      respect to respiratory diseases in males, where the shared environment plays an
      important role.

PMID- 14673945
TI  - Probabilistic approach to developing nephropathy in diabetic patients with
      retinopathy.
AB  - It is well known that diabetes is a risk factor for many complications including
      diabetic retinopathy and nephropathy. An interesting question is whether a
      diabetic patient who has developed a retinopathy develops a nephropathy sooner.
      We approached this problem by calculating the conditional probability that a
      diabetic patient will develop a second complication, given that they had already
      developed the first complication. We also propose the application of Bayes'
      formula to estimate the probability of developing the second complication, given
      that the first complication had developed previously. We compared these two
      methods by applying them to analyse 5473 patients with type 2 diabetes. The
      results of our experience are described.

PMID- 14673946
TI  - On parametric empirical Bayes methods for comparing multiple groups using
      replicated gene expression profiles.
AB  - DNA microarrays provide for unprecedented large-scale views of gene expression
      and, as a result, have emerged as a fundamental measurement tool in the study of
      diverse biological systems. Statistical questions abound, but many traditional
      data analytic approaches do not apply, in large part because thousands of
      individual genes are measured with relatively little replication. Empirical Bayes
      methods provide a natural approach to microarray data analysis because they can
      significantly reduce the dimensionality of an inference problem while
      compensating for relatively few replicates by using information across the array.
      We propose a general empirical Bayes modelling approach which allows for
      replicate expression profiles in multiple conditions. The hierarchical mixture
      model accounts for differences among genes in their average expression levels,
      differential expression for a given gene among cell types, and measurement
      fluctuations. Two distinct parameterizations are considered: a model based on
      Gamma distributed measurements and one based on log-normally distributed
      measurements. False discovery rate and related operating characteristics of the
      methodology are assessed in a simulation study. We also show how the posterior
      odds of differential expression in one version of the model is related to the
      ratio of the arithmetic mean to the geometric mean of the two sample means. The
      methodology is used in a study of mammary cancer in the rat, where four distinct
      patterns of expression are possible.

PMID- 14673947
TI  - Chronic activity of ectopic type 1 fibroblast growth factor receptor tyrosine
      kinase in prostate epithelium results in hyperplasia accompanied by
      intraepithelial neoplasia.
AB  - BACKGROUND: Ectopic expression of fibroblast growth factor receptor 1 (FGFR1)
      tyrosine kinase in epithelial cells is associated with progression of prostate
      cancer. Ectopic expression by transfection of FGFR1 in premalignant epithelial
      cells from nonmalignant Dunning tumors accelerated time-dependent progression of
      epithelial cells to malignancy. This study was designed to test the effect of
      chronic androgen-dependent ectopic activity of FGFR1 in the normal adult mouse
      epithelium by gene targeting. MATERIALS AND METHODS: Constitutively active FGFR1
      (caFGFR1) was targeted to prostate epithelial cells using the androgen-dependent
      probasin (PB) promoter. Prostate tissues of three strains were characterized over
      a period of 2 years by HE staining, immunohistochemical analyses for cytokeratin
      and alpha-actin, and rate of androgen-induced regeneration after castration.
      RESULTS: Relative to wildtype littermates, transgenic mice showed increased
      overall size, hyperplasia in epithelial, and, to a lesser extent, stromal
      compartments and nuclear atypia in epithelial cells of the prostate with
      increasing age. Androgen-induced regeneration after castration was enhanced at
      day 3 by two-fold in mice expressing ectopic caFGFR1. CONCLUSIONS: The ectopic
      presence and chronic activation of FGFR1 in mouse prostate epithelial cells
      induces progressive prostate intraepithelial neoplasia. These results confirm
      results suggested by the transplantable Dunning tumor and cell culture models
      that, in contrast to homeostasis-promoting resident FGFR2, chronic ectopic FGFR1
      kinase activity in the epithelium disrupts homeostasis between stroma and
      epithelium. Although insufficient alone, it may cooperate with other oncogenic
      changes to promote epithelial cells down the path to malignancy.

PMID- 14673948
TI  - Characterization of a transplantable hormone-responsive human prostatic cancer
      xenograft TEN12 and its androgen-resistant sublines.
AB  - BACKGROUND: Models for human prostate cancer can facilitate the study of
      resistance to endocrine therapy, aid drug discovery, and pre-clinical assessment.
      METHODS: Characteristics thought relevant to the growth in athymic nude mice of
      TEN12, an androgen-dependent transplantable prostatic cell line derived from a
      primary prostate carcinoma, and its two androgen-independent sublines, TEN12F and
      TEN12C, have been assessed immunocytochemically. RESULTS: The xenografts of the
      parental TEN12 line are moderately differentiated with both papillary and
      glandular regions, pleomorphic nuclei and abundant mitotic figures and are
      extremely vascular. The cells express androgen receptor (AR), PSA, VEGF, EGFR, c
      erbB2, and TGFalpha. Both TEN12F and TEN12C xenografts possessed a more
      anaplastic morphology and displayed significantly lower growth rates, reduced
      blood vessel density (BVD), decreased MIB-1 antigen and E-cadherin expression and
      increased cytoplasmic AR and HSP90 staining. Elevated EGFR (membrane) but not c
      erbB2 expression was demonstrated in the TEN12F line only. Castration of mice
      bearing TEN12 xenografts rapidly induced the appearance of cytoplasmic AR in the
      cells, PSA levels decreased initially but recovered to below pre-castration
      levels whilst reduced TGFalpha and loss of VEGF expression was seen in the long
      term castrates. CONCLUSIONS: TEN12 and its sublines offer additional in vivo
      models to study the factors involved in the progression of prostatic cancer to
      androgen-independence.

PMID- 14673949
TI  - Effect of a short CAG (glutamine) repeat on human androgen receptor function.
AB  - BACKGROUND: The human androgen receptor (AR) gene contains an uninterrupted CAG
      repeat that is polymorphic in length in the general population (range, 11-31
      CAG's; median, 21). The CAG repeat encodes a glutamine repeat in the N-terminal
      transactivation domain of the AR protein. We previously reported that a 17-CAG AR
      gene was much more common in a cohort of men with prostate cancer (8.5%) than in
      the general European American population (1.3%). This suggested that a 17-CAG
      repeat may have pathophysiological consequences. The goal of the present study
      was to directly test the hypothesis that a 17-CAG repeat might uniquely affect
      androgen action in human prostate cancer cells. METHODS: DU145 cells, lacking
      endogenous AR, were transiently transfected with an AR expression plasmid (with a
      CAG repeat ranging in length from 14 to 25) and an androgen-responsive reporter
      plasmid (PSA-luciferase). RESULTS: We found a significant effect of CAG repeat
      length on AR protein levels per unit amount of DNA transfected (one-way ANOVA, P
      = 0.02), indicating the need to express transactivation data per unit amount of
      AR protein. CAG17 AR had 40% more transactivation activity per unit amount of AR
      protein than CAG21 AR (P < 0.01). CONCLUSIONS: Thus, an AR with a 17-CAG repeat
      may mediate more efficacious growth stimulation of androgen-dependent prostate
      epithelial cells, and thereby increase the risk that prostate cancer cells
      develop more efficiently into a clinically significant cancer.

PMID- 14673950
TI  - Messenger RNA levels and enzyme activities of 5 alpha-reductase types 1 and 2 in
      human benign prostatic hyperplasia (BPH) tissue.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) development requires testicular
      androgens and aging. The principle prostatic androgen is dihydrotestosterone
      (DHT). Testosterone is converted to DHT by the enzyme 5 alpha-reductase. Two
      distinct 5 alpha-reductase enzymes, types 1 and 2, have been identified. While
      some studies have suggested that type 2 isoenzyme predominates in the prostate,
      studies on the prostatic localization of the two isoenzymes are controversial.
      The purpose of this study was to determine the quantitative expressions of 5
      alpha-reductase types 1 and 2 in BPH tissues. METHODS: We examined the
      localizations of types 1 and 2 isoenzymes in BPH tissues using
      immunohistochemical staining and a real-time quantitative RT-PCR assay using the
      TaqMan system. We measured the enzyme activities of types 1 and 2 at pH values of
      7.5 and 5.0, respectively. RESULTS: Our immunohistochemical study showed that
      type 1 isoenzyme was expressed predominantly in epithelial cells, whereas type 2
      isoenzyme was expressed in both stromal and epithelial cells. The real-time RT
      PCR assay demonstrated that the copy numbers of type 1 isoenzyme mRNA were
      significantly higher than those of type 2 isoenzyme mRNA. There were significant
      associations between enzyme activity at pH 7.5 and type 1 isoenzyme mRNA
      expression, and between the activity at pH 5.0 and type 2 mRNA expressions.
      CONCLUSIONS: We demonstrated that 5 alpha-reductase type 1 had a specific enzyme
      activity in the prostate, which supports the hypothesis that the type 1 isoenzyme
      may play a significant role in maintaining prostate enlargement along with the
      type 2 isoenzyme.

PMID- 14673951
TI  - Prostate carcinoma cells that have resided in bone have an upregulated IGF-I
      axis.
AB  - BACKGROUND: Prostate cancer (PC) has a propensity to metastasize to the skeleton,
      inducing an osteoblastic response in the host. Recent epidemiological studies
      have suggested that circulating IGF-I may be important for both the pathogenesis
      and dissemination of PC. We have postulated that tumor secreted IGF-I in
      conjunction with endogenous IGF-I contributes to the osteoblastic phenotype
      characteristic of metastatic PC. METHODS: To test this thesis we studied the
      established LNCaP PC progression model consisting of three genetically related
      human PC cell lines. RESULTS: Using RIA, we found serum-free conditioned media
      (CM) of LNCaP and C4-2 had no measurable IGF-I, whereas IGF-I was easily detected
      in CM from C4-2B cells at 24 hr (i.e., 1.8 +/- 0.53 ng/mg cell protein). Real
      time PCR of IGF-I mRNA showed that C4-2B expressed 100-fold more IGF-I mRNA than
      LNCaP cells. In addition, C4-2B expression of IGF-I mRNA was substantially
      increased in the presence of exogenous IGF-I to nearly twofold. While IGFBP-3 and
      IGFBP-1 were not detectable in the CM of any PC line, all cells secreted IGFBP-2.
      C4-2B cells produced 40% more IGFBP-2 than LNCaP or C4-2 cells (C4-2B at 167 +/-
      43 ng/mg cell protein). RANKL, a product of bone stromal cells, was also
      differentially expressed: LNCaP had threefold higher RANKL mRNA compared to C4-2
      and C4-2B and at least equivalent protein expression. CONCLUSIONS: Our results
      suggest that PC cells that have metastasized to bone have an upregulated IGF-I
      regulatory system. This suggests an activated IGF-I axis contributes to the host
      PC interaction in promoting osteoblastic metastases.

PMID- 14673952
TI  - Association between captopril, other antihypertensive drugs and risk of prostate
      cancer.
AB  - BACKGROUND: There has been some debate on the existence of an association between
      hypertension, antihypertensive medications and cancer risk. METHODS: We performed
      a nested case-control study to assess the association between the risk of
      prostate cancer and the use of the angiotensin converting enzyme (ACE)-inhibitor
      captopril, and other antihypertensive drugs. We used data from the General
      Practice Research Database in UK. RESULTS: We found an incidence rate of prostate
      cancer of 1.61 per 1,000 person-years among male patients aged 50-79 years old.
      Patients with a history of benign prostatic hyperplasia and/or prostatism carried
      a two-fold greater risk of prostate cancer than those without such antecedents.
      None of the other studied co-morbidities were associated with prostate cancer. We
      found that users of captopril had a relative risk of 0.7 (95% CI: 0.4-1.2) to
      develope prostate cancer. None of the other studied individual ACE-inhibitors
      shared a similar effect with the one observed for captopril. CONCLUSIONS: No
      clear association was apparent between the use of antihypertensive drugs and
      prostate cancer. However, specific focus on users of captopril showed a lower
      risk of subsequent prostate cancer. Further research is needed to explore this
      association.

PMID- 14673953
TI  - Neutralizing VEGF bioactivity with a soluble chimeric VEGF-receptor protein flt(1
      3)IgG inhibits testosterone-stimulated prostate growth in castrated mice.
AB  - BACKGROUND: Recent studies show that testosterone-stimulated growth of the
      glandular tissue in the ventral prostate in adult castrated rats is preceded by
      increased epithelial VEGF synthesis, endothelial cell proliferation, vascular
      growth, and increased blood flow. These observations suggest that testosterone
      stimulated prostate growth could be angiogenesis dependent, and that VEGF could
      play a central role in this process. METHODS: Adult male mice were castrated and
      after 1 week treated with testosterone and vehicle, or with testosterone and a
      soluble chimeric VEGF-receptor flt(1-3)IgG protein. RESULTS: Treatment with
      testosterone markedly increased endothelial cell proliferation, vascular volume,
      and organ weight in the ventral prostate lobe in the vehicle groups, but these
      responses were inhibited but not fully prevented by anti-VEGF treatment. The
      testosterone-stimulated increase in epithelial cell proliferation was unaffected
      by flt(1-3)IgG, but endothelial and epithelial cell apoptosis were increased in
      the anti-VEGF compared to the vehicle-treated groups. CONCLUSIONS: This study
      suggests that testosterone stimulates vascular growth in the ventral prostate
      lobe indirectly by increasing epithelial VEGF synthesis and that this is a
      necessary component in testosterone-stimulated prostate growth.

PMID- 14673955
TI  - Difference of cancer core distribution between first and repeat biopsy: In
      patients diagnosed by extensive transperineal ultrasound guided template prostate
      biopsy.
AB  - BACKGROUND: We performed extensive transperineal ultrasound guided template
      prostate biopsy and evaluated cancer core distribution. METHODS: From August 2000
      to May 2002, 113 men with prostate specific antigen levels between 4.0 and 10.0
      ng/ml underwent template biopsy. Eighty-six had no previous biopsy (first group)
      and 27 had previous transrectal sextant biopsies (repeat group). A mean of 18.4
      biopsy cores were taken. We defined the region over 2 cm from the rectal face of
      the prostate as the anterior region and the other as the posterior. RESULTS:
      Cancer was detected in 49 of 113 (43%) men. Forty-two were in the first group and
      seven in the repeat group. In the first group, the cancer core rate (cancer core
      number/biopsy core number) in the anterior region (7.0%) had no difference from
      that in the posterior region (8.6%) (P = 0.7111). But in the repeat group, the
      cancer core rate in the anterior region (4.6%) was higher than in the posterior
      (1.5%) (P < 0.0001). CONCLUSIONS: These results suggest that transrectal sextant
      biopsies miss more cancers in the anterior region than in the posterior. We
      believe template technique has an advantage to be able to detect cancer equally
      in the anterior and posterior.

PMID- 14673954
TI  - Fibroblast growth factor-1 transcriptionally induces membrane type-1 matrix
      metalloproteinase expression in prostate carcinoma cell line.
AB  - BACKGROUND: We and others have shown that the matrix metalloproteinases, MT1-MMP
      is overexpressed in human prostate PIN lesions and invasive cancers compared to
      normal prostate epithelium. However, the mechanism for this overexpression is not
      understood. Evidence from our laboratory and others has indicated that fibroblast
      growth factors (FGFs) can regulate the expression of certain matrix
      metalloproteinase. In addition, human prostate fibroblasts are known to express
      certain FGFs, including FGF-1. The purpose of the work in this paper was to
      determine the mechanism involved in FGF-1 induced MT1-MMP expression in prostate
      carcinoma cells. METHODS: We tested the ability of recombinant FGF-1 to induce
      MT1-MMP expression in prostate carcinoma cell line, LNCaP cells. We measured the
      MT1-MMP message by using Northern analyses and protein levels by Western analysis
      after FGF-1 treatment. Downstream signaling was investigated using dominant
      negative constructs for FGFR-1 and signal transducer and activator of
      transcription-3 (STAT3). Transient transfection was performed using reporter
      plasmids of the MT1-MMP gene promoter region (7.2 kb) linked to the firefly
      luciferase gene in the pGL3-Basic vector. For dominant negative studies FGFR-1
      dominant negative plasmid in PCEP4 vector or STAT3 dominant negative plasmid in
      pCMV-1 vector was co-transfected with the MT1-MMP reporter plasmid. RESULTS:
      Recombinant FGF-1 significantly induced MT1-MMP expression in LNCaP prostate
      carcinoma cells. MT1-MMP message increased with FGF-1 treatment compared to that
      of untreated control LNCaP cells. Quantitation by digital image analysis revealed
      that this increase was twofold over untreated LNCaP cells. Treatment of pGL3-MT1
      MMP-luciferase transfected cells with FGF-1 resulted in a twofold to fourfold
      increase in luciferase enzyme activity compared with untreated cells. Co
      transfection of LNCaP with human MT1-MMP reporter construct and a dominant
      negative FGFR1 mutant showed that FGF-1-induced MT1-MMP expression in LNCaP cells
      was completely inhibited by the mutated FGFR-1, indicating that FGF receptor
      (FGFR) activation is necessary for induction of MT1-MMP. Further, expression of
      dominant negative STAT3 inhibited the FGF-1-induced transactivation of the human
      MT1-MMP 7.2-kb promoter. CONCLUSIONS: From these data, we conclude that FGF-1
      induces MT1-MMP expression in prostate carcinoma cells through a transcriptional
      mechanism mediated through the FGFR and the transcription factor, STAT3. These
      results confirm earlier data indicating that acidic FGF and STAT3 are involved in
      the signaling leading to the expression of a MMP. Our findings support the idea
      that paracrine and autocrine factors play an important role in the regulation of
      MT1-MMP in human prostate carcinoma cells.

PMID- 14673956
TI  - Proliferation of prostate cancer cells and activity of neutral endopeptidase is
      regulated by bombesin and IL-1beta with IL-1beta acting as a modulator of
      cellular differentiation.
AB  - BACKGROUND: Neutral endopeptidase (NEP) is a cell-surface bound enzyme that
      cleaves and inactivates neuropeptides such as bombesin and substance P and is
      involved in the transition from hormonally regulated androgen-dependent prostate
      cancer (PC) to androgen-independent PC. Neuropeptides are implicated in growth
      regulation of different cell types and function as transmitters between the
      neuroendocrine and the immune system. METHODS: NEP-expression, enzymatic activity
      of the membrane bound protein, cell proliferation, procalcitonin (PCT)
      production, and secretion as well as changes in cell morphology of prostatic
      cells were evaluated after treatment with the immunomodulatory cytokine
      interleukin-1beta (IL-1beta), neuropeptides (bombesin, substance P), and
      neuropeptide-conditioned media derived from a human neuroendocrine cell line.
      RESULTS: Incubation of LNCaP tumor cells with IL-1beta resulted in a diminished
      proliferative activity, induction of neurite-like outgrowth which was accompanied
      by the formation of tubular-type mitochondria typical for neuronal/neuroendocrine
      cells, and an increased production and secretion of PCT. Conversely,
      proliferation of prostatic stromal cells was enhanced by the cytokine coming
      along with an increased number of Golgi-apparatuses and ER-cisternae. Bombesin
      had an antimitotic effect on LNCaP, but not on stromal cells. Substance P did not
      influence the growth of any of the cell types investigated, whereas neuropeptide
      conditioned media exerted a slightly mitogenic effect on both cell types. The
      activity of LNCaP cell-surface bound NEP was enhanced by bombesin, but was
      diminished by substance P and neuropeptide-conditioned media. CONCLUSIONS:
      Proliferation and activity of neuropeptide degrading NEP is regulated differently
      by immunomodulatory substances in PC cells and cells derived from the prostatic
      stroma with IL-1beta being a potent modulator of cellular differentiation and a
      potential target for anticancer drug design in PC cells.

PMID- 14673957
TI  - Activation of the Raf-1/MEK/Erk kinase pathway by a novel Cdc25 inhibitor in
      human prostate cancer cells.
AB  - BACKGROUND: The serine/threonine kinase Raf-1 is a major regulator of the mitogen
      activated protein kinase (MAPK) pathway, which has been associated with the
      progression of prostate cancer to the more advanced and androgen-independent
      disease. Cdc25A phosphatase has been implicated in the regulation of Raf-1 and
      the MAPK pathway. METHODS: We used a novel and potent Cdc25A inhibitor, 2,3-bis
      [2-hydroxyethylsulfonyl]-[1,4] naphthoquinone (NSC 95397), and its congener (2
      mercaptoethanol)-3-methyl-1, 4-naphthoquinone (NSC 672121) to study the role of
      Cdc25A on the MAPK pathway in human prostate cancer cells. RESULTS: We found Raf
      1 physically interacted with Cdc25A in PC-3 and LNCap cells and inhibitors of
      Cdc25A induced both extracellular signal-regulated kinase (Erk) activation and
      Raf-1 tyrosine phosphorylation. NSC 95397 attenuated Cdc25A and Raf-1
      interactions due to accelerated degradation of Cdc25A, which was mediated by
      proteasome degradation. The MAPK kinase (MEK) inhibitor U0126 completely
      inhibited Erk activation by NSC 95397 and NSC 672121. CONCLUSIONS: These results
      indicate Cdc25A phosphatase regulates Raf-1/MEK/Erk kinase activation in human
      prostate cancer cells.

PMID- 14673958
TI  - Fatigue fractures suggesting clinical monarthritis.
AB  - OBJECTIVE: To examine etiologic factors, clinical features, and outcome in a
      series of consecutive patients with fatigue fractures diagnosed at a rheumatology
      division for a defined population over a 14-month period. METHODS: A prospective
      study of the patients diagnosed with fatigue fracture at the rheumatology
      division of the Hospital Xeral-Calde (Lugo, Spain) between July 2000 and August
      2001 was conducted. Hormonal status, body mass index, lifestyle, job, underlying
      diseases, and drug intake, which might be attributable risk factors for the
      stress fracture, were assessed. In all the patients a followup of at least 6
      months was required. RESULTS: Six consecutive patients (4 women) fulfilled the
      inclusion criteria. All of them were younger than 65 years (median 45 years;
      range 36-64 years) and had a body mass index lower than 25. In this series no
      distinctive occupation was found. The delay to diagnosis since the onset of
      symptoms ranged from 0.5 to 6 months (median 1.5). All patients but 1 were sent
      to the rheumatology division because of a clinical diagnosis of monarthritis.
      Pain and swelling were the presenting symptoms. Conventional radiographs were
      normal and fine needle aspiration of the joints yielded negative results for
      microcrystals and organisms. Magnetic resonance imaging disclosed the presence
      and site of fracture in all the cases. Sequelae of mechanical pain and subsequent
      osteoarthritis were observed in the 3 cases with longer delay to diagnosis.
      CONCLUSION: Fatigue fractures are not exceptional in unselected adults.
      Rheumatologists should consider this diagnosis in patients presenting with
      monarthritis. Physician awareness is required to prevent the development of
      sequelae.

PMID- 14673959
TI  - Leflunomide use during the first 33 months after food and drug administration
      approval: experience with a national cohort of 3,325 patients.
AB  - OBJECTIVE: To describe leflunomide (LEF) use in a national cohort of 3,325
      veterans. METHODS: Prescriptions for LEF and 9 disease-modifying antirheumatic
      drugs written between October 1998 and June 2001 at all Veterans Affairs (VA)
      medical centers were obtained from VA national databases. RESULTS: LEF was
      initiated with a loading dose of 100 mg daily for 3 days in 61% of patients, and
      42% of patients discontinued LEF. LEF was more likely to be discontinued if a 3
      day 100-mg loading dose was prescribed, patients were younger than 44 years or
      older than 75 years, or reported an annual family income <$60,000. Review of
      medical records of 291 discontinuers revealed that the most common reasons for
      discontinuation were inefficacy (30%), gastrointestinal symptoms (29%),
      medication noncompliance or lost to followup (14%), and elevated liver enzymes
      (5%). CONCLUSION: LEF is relatively safe in clinical practice. The VA's national
      databases provide an excellent, inexpensive resource for postmarketing evaluation
      of rheumatologic medications.

PMID- 14673960
TI  - Association of nitrate use with risk of new radiographic features of hip
      osteoarthritis in elderly white women: the study of osteoporotic fractures.
AB  - OBJECTIVE: To examine the association between nitrate medication use and the
      development of new radiographic findings of hip osteoarthritis (OA) in elderly
      women. METHODS: Pelvic radiographs were obtained at baseline and a mean of 8.3
      years later in 5,987 women, age > or =65 years at the baseline examination of the
      Study of Osteoporotic Fractures. Atlas-standardized individual radiographic
      features (IRFs) of OA were assessed and minimal joint space was measured on
      paired films. New radiographic findings of hip OA were defined as the development
      in hips free of these findings at baseline: 1) joint space narrowing (JSN), which
      consisted of either a MJS < or =1.5 mm or an IRF score indicating lateral JSN >
      or =2 or medial JSN > or =3; 2) an IRF score for osteophytes of > or =2 in any
      location; or 3) a summary grade of 2 or more (at least 2 IRFs present). Nitrate
      use was recorded by interview at years 6 and 8. Logistic and linear regression
      analyses were performed to determine the association of nitrate use with new
      radiographic findings of hip OA, adjusting for age, weight, height, bone mineral
      density, and estrogen. RESULTS: Compared with no reported use of nitrates, we
      found significant associations between use of nitrates at 1 clinic visit and new
      JSN (odds ratio [OR] 1.94, 95% confidence interval [95% CI] 1.18-3.17, P =
      0.009), new osteophyte formation (OR 1.70, 95% CI 1.03-2.88, P = 0.04), and any
      new radiographic finding of hip OA or total hip arthroplasty for OA (OR 1.71, 95%
      CI 1.16-2.52, P = 0.007). Any nitrate use was associated with an increased risk
      of developing summary grade 3 or greater hip OA (OR 1.84, 95% CI 1.03-3.31, P =
      0.041), but not with any other incident findings of OA. CONCLUSION: Older women
      using nitrates may have an increased risk of developing new radiographic findings
      of hip OA.

PMID- 14673961
TI  - Access to pediatric rheumatology care in the United States.
AB  - OBJECTIVE: To describe rheumatology providers, depict their availability, and
      determine the extent to which internist rheumatologists may expand access to care
      for children with rheumatic diseases. METHODS: Using data from the American
      College of Rheumatology and the Bureau of Health Professions Area Resource File,
      we generated a national map of providers' practice locations and calculated
      distances between each county and the nearest rheumatologist. We also performed a
      logit analysis to identify provider and county characteristics that were
      associated with internist rheumatologists' willingness to treat children.
      RESULTS: Approximately 50% of the under 18 population in the United States live
      within 50 miles of a pediatric rheumatologist and nearly 90% live within 50 miles
      of a pediatric rheumatologist or an internist rheumatologist who treats children.
      Internist rheumatologists in private practice were 3 times as likely as those in
      medical schools to treat children (P < 0.001). Likewise, internist
      rheumatologists who live 200 or more miles from a pediatric rheumatologist were
      more than twice as likely to treat children as those who lived within 10 miles of
      a pediatric rheumatologist (P < 0.001). CONCLUSIONS: Our analysis suggests that
      internist rheumatologists are more geographically diffuse than pediatric
      rheumatologists and act as substitutes for pediatric rheumatologists in those
      regions that lack such providers. Research is needed to understand the role of
      internist rheumatologists in caring for children with rheumatic diseases and the
      quality of the care that they provide to this population.

PMID- 14673962
TI  - Management of depression in rheumatoid arthritis: a combined pharmacologic and
      cognitive-behavioral approach.
AB  - OBJECTIVE: To examine the effectiveness of cognitive-behavioral and pharmacologic
      treatment of depression in rheumatoid arthritis (RA). METHODS: Subjects (n = 54)
      with confirmed diagnoses of both major depression and RA were randomly assigned
      to 1 of 3 groups: 1) cognitive-behavioral/pharmacologic group (CB-PHARM), 2)
      attention-control/pharmacologic group, or 3) pharmacologic control group.
      Measures of depression, psychosocial status, health status, pain, and disease
      activity were collected at baseline, posttreatment (10 weeks), 6-month followup,
      and 15-month followup. Data were analyzed to compare the treatment effectiveness
      of the groups; data also were aggregated to examine the effects of antidepressive
      medication over time. Lastly, a no-treatment control group was defined from a
      cohort of persons who declined participation. RESULTS: Baseline comparisons on
      demographic and dependent measures revealed a need to assess covariates on age
      and education; baseline scores on dependent measures also were entered as
      covariates. Analyses of covariance revealed no statistically significant group
      differences at postintervention, 6-month followup, or 15-month followup, except
      higher state and trait anxiety scores for the CB-PHARM group at the 15-month
      followup. In the longitudinal analyses of the effects of antidepressive
      medication, significant improvement in psychological status and health status
      were found at posttreatment, 6-month followup, and 15-month followup, but no
      significant improvements were shown for pain or disease activity. In addition,
      the comparison of the aggregated pharmacologic group with a no-treatment group
      revealed a statistically significant benefit for the 3 groups that received the
      antidepressive medication. CONCLUSION: In persons with RA, cognitive-behavioral
      approaches to the management of depression were not found to be additive to
      antidepressant medication alone, but antidepressant intervention was superior to
      no treatment.

PMID- 14673963
TI  - Spirituality, well-being, and quality of life in people with rheumatoid
      arthritis.
AB  - OBJECTIVE: To evaluate spirituality, well-being, and quality of life (QOL) among
      people with rheumatoid arthritis (RA). METHODS: Questionnaires assessing positive
      and negative affect, depression, QOL and spirituality were completed. Disease
      activity was assessed by rheumatologic examination. RESULTS: Women (n = 62) had a
      mean (+/- SD) age of 53.0 (+/- 13.0) years with 12 (+/- 13) swollen and tender
      joints (STJ). Men (n = 15) were 61.9 (+/- 13.0) years with 7 (+/- 11) STJ.
      Disease activity was associated (P < 0.05) positively with depression (r = 0.23),
      pain (r = 0.26), poorer self-ratings of health (r = 0.29) and physical role
      limitations (r = 0.26). Spirituality was associated directly with positive affect
      (r = 0.26) and higher health perceptions (r = 0.29). In multiple regression,
      spirituality was an independent predictor of happiness and positive health
      perceptions, even after controlling disease activity and physical functioning,
      for age and mood. CONCLUSION: Spirituality may facilitate emotional adjustment
      and resilience in people with RA by experiencing more positive feelings and
      attending to positive elements of their lives.

PMID- 14673964
TI  - Validation of a Japanese version of the Stanford Health Assessment Questionnaire
      in 3,763 patients with rheumatoid arthritis.
AB  - OBJECTIVE: To develop and validate a self-administered instrument for measuring
      functional status in Japanese-speaking rheumatoid arthritis patients. METHODS: We
      translated the Stanford Health Assessment Questionnaire (HAQ) into Japanese
      (original HAQ), and then made a tentative Japanese version of the HAQ (J-HAQ)
      with culturally appropriate modifications of the arising, eating, and reach
      category questions. The questionnaire was then administered to 3,763 RA patients
      (82.6% female; mean age 58.0 years; mean onset age 47.4 years; mean disease
      duration 10.5 years). RESULTS: This instrument showed excellent internal
      reliability (Cronbach's alpha = 0.927), with a mean interitem correlation of
      0.60. For the arising category question, the J-HAQ asks about arising from a
      futon in addition to a bed because futons are still common in Japanese culture.
      Arising from a futon is generally more difficult for disabled individuals than is
      arising from a bed, so the arising score was higher in the J-HAQ (mean score
      0.82) than in the original HAQ (0.48). The average scores for the eating and
      reach categories were virtually identical for the original HAQ and the J-HAQ,
      with correlation coefficients of 0.979 and 0.926, respectively. Thus, the overall
      disability index (average of the scores for all functional areas) was higher in
      the J-HAQ (0.81) than in the original HAQ (0.76), although the correlation
      coefficient was high (0.993). The test-retest reliability value (0.92), studied
      at a 1-week interval, revealed identical disability index scores measured on the
      2 occasions. CONCLUSION: The final version of the J-HAQ is a valid and reliable
      instrument for measuring functional status in Japanese-speaking RA patients.

PMID- 14673965
TI  - Effects of concurrent strength and endurance training in women with early or
      longstanding rheumatoid arthritis: comparison with healthy subjects.
AB  - OBJECTIVE: To investigate the effects of a 21-week concurrent strength and
      endurance training protocol on physical fitness profile in women with early or
      longstanding rheumatoid arthritis (RA) compared with healthy subjects. METHODS:
      Twenty-three female patients with RA volunteered for the study. Twelve had early
      RA and eleven had longstanding RA. Twelve healthy women served as controls.
      Maximal strength of different muscle groups was measured by dynamometers, walking
      speed with light cells, and vertical squat jump on the force platform to mirror
      explosive force. Maximal oxygen uptake was measured by gas analyzer. Six training
      sessions (3 strength training and 3 endurance training) were carried out in a 2
      week period for 21 weeks. RESULTS: The training led to large gains in maximal
      strength both in women with RA and in healthy women (P < 0.043-0.001). The
      strength gains were accompanied by increases in walking speed (P < 0.034-0.001)
      and vertical squat jump (P < 0.034-0.001). Significant improvements also occurred
      in maximal aerobic capacity in all groups (P < 0.023-0.014). CONCLUSIONS: Both
      early and longstanding RA patients with stable disease can safely improve all
      characteristics of their physical fitness profile using a progressive concurrent
      strength and endurance training protocol.

PMID- 14673966
TI  - Validation of a rheumatoid arthritis health-related quality of life instrument,
      the CSHQ-RA.
AB  - OBJECTIVE: To test the validity and reliability of a newly developed disease
      specific multidimensional quality of life instrument: the Cedars-Sinai Health
      Related Quality of Life Instrument (CSHQ-RA). METHODS: A total of 350 rheumatoid
      arthritis (RA) patients were asked to complete the CSHQ-RA at 2 time points (4
      weeks apart). Patients also completed the Medical Outcomes Study Short Form 36
      (SF-36) and the Stanford Health Assessment Questionnaire (HAQ) Disability Index
      (DI) at the second time point. Construct validity was tested, using Pearson's
      correlations, by comparing subscale scores on the CSHQ-RA to those obtained from
      the mental component summary (MCS) and physical component summary (PCS) of the SF
      36. HAQ DI scores were used to assess the discriminant validity of the CSHQ-RA.
      Intraclass correlation coefficients (ICCs) were used to assess test-retest
      reliability. RESULTS: Response rates for the first and second survey were 83%
      (291) and 93% (276), respectively; 84% of respondents were women, and mean age
      was 57 years. Mean scores +/- SDs on instruments were: HAQ 0.73 +/- 0.69; MCS 49
      +/- 12; and PCS 33 +/- 11. Pearson's correlations between the CSHQ-RA subscale
      scores and the SF-36 scores ranged from 0.55 to 0.76 (P < 0.001). Analysis of
      variance indicate that scores on the CSHQ-RA discriminated between levels of
      physical disability as measured by the HAQ (P < 0.001). Test-retest reliability
      was demonstrated in the instrument's subscale scores (ICC 0.70-0.90). CONCLUSION:
      These results support the construct validity, discriminant validity, and
      reliability of the CSHQ-RA as a measure that captures the impact of RA on
      patients' health-related quality of life.

PMID- 14673968
TI  - Participatory patient-physician communication and morbidity in patients with
      systemic lupus erythematosus.
AB  - OBJECTIVE: To examine associations between active patient-physician communication
      and measures of morbidity in patients with systemic lupus erythematosus (SLE).
      METHODS: Audiotapes of routine visits between 79 women with SLE and their
      rheumatologists were coded for active patient participation and the degree of
      patient-centered communication of the physician, using a validated coding scheme.
      Measures of SLE activity, functional disability, and permanent organ damage were
      recorded at the same visit. Permanent organ damage was reassessed in 68 patients
      after a median of 4.7 years. RESULTS: Patients who participated more actively in
      their visits had less permanent organ damage, as measured by the Systemic Lupus
      International Collaborating Clinics/American College of Rheumatology Damage
      Index, and tended to accrue less organ damage over time. There were no
      associations between either active patient participation or physicians' patient
      centered communication scores and measures of SLE activity or functional
      disability. CONCLUSIONS: Patients with SLE who participated more actively in
      their visits had less permanent organ damage, suggesting that involving patients
      more in their care may decrease morbidity.

PMID- 14673967
TI  - Thyroid dysfunction in primary Sjogren's syndrome: a long-term followup study.
AB  - OBJECTIVE: To evaluate the prevalence of thyroid dysfunction and related
      autoantibodies in patients with primary Sjogren's syndrome (pSS), and to
      determine whether these abnormalities develop over time. METHODS: pSS patients (n
      = 137) and controls (n = 120) were investigated for thyroid dysfunction and for
      the presence of anti-thyroid peroxidase antibody (anti-TPO) and antithyroglobulin
      antibody (ATG). Followup time for patients was 1-16 years, and 72 of the 120
      controls were reevaluated 3 years after initial evaluation. RESULTS: Thyroid
      disease was more frequent in the pSS patients than in the controls (30% versus
      4%; P < 10(-4)), as were anti-TPO and ATG (11% versus 3%; P < 0.02, and 3% versus
      1%, not significant). Ten of 107 euthyroid pSS patients dropped out of the study,
      and thyroid dysfunction became apparent at followup in 12 of the remaining 97.
      Most of the patients with thyroid-related autoantibodies at entry developed
      autoimmune thyroid disease thereafter. CONCLUSION: Thyroid dysfunction is
      frequent in pSS patients, and those prone to develop thyroid disorders are
      identified by thyroid-related autoantibodies, or by rheumatoid factor and anti
      Ro/SSA activity.

PMID- 14673969
TI  - Domains of health-related quality of life important to patients with giant cell
      arteritis.
AB  - OBJECTIVE: To determine aspects of quality of life (QOL) important to people with
      giant cell arteritis (GCA). METHODS: We explored the domains of QOL affected by
      GCA in audiotaped focus groups. We then created an Importance Rating
      Questionnaire (IRQ) by constructing questions related to the domains most
      frequently mentioned. Of 214 GCA patients to whom the IRQ was sent, 145 (68%)
      responded. We calculated frequencies of responses and then ranked items by the
      proportion selecting the top category of importance and also according to a mean
      item rank. We compared the domains of QOL covered by the IRQ with those in the
      Short Form 12 (SF-12). RESULTS: The highest rated QOL item was "losing sight in
      both eyes permanently." Of the top 20 items, 12 were in domains not covered
      directly by the SF-12. CONCLUSION: We have identified aspects of QOL important to
      GCA patients. Assessment of QOL in GCA should include vision and other domains
      that are not included in standard QOL questionnaires.

PMID- 14673970
TI  - Investigation of quality of life, mood, pain, disability, and disease status in
      primary systemic vasculitis.
AB  - OBJECTIVE: To assess quality of life (QOL) and psychological adjustment in
      primary systemic vasculitis (PSV), and to assess their relationship to disease
      related measures. METHODS: Fifty-one PSV patients completed questionnaires
      assessing QOL (Short Form 36 [SF-36]), disability (Health Assessment
      Questionnaire [HAQ]), and mood (Hospital Anxiety and Depression Scale [HADS]).
      Illness-related measures, disease activity, and permanent damage scores (the
      Birmingham Vasculitis Damage Index [BVDI] modified, and the Birmingham Vasculitis
      Activity Scale modified) were collected. Aspects of the HAQ's psychometric
      properties were evaluated. RESULTS: PSV patients' SF-36 scores, except for mental
      health, were significantly lower than the norms, indicating poorer QOL. Using the
      HADS, 43.2% of patients reported increased anxiety symptoms and 25.5% increased
      depressive symptoms. Patients with increased pain when compared with those with
      little or no pain had significantly impaired scores in all SF-36 subscales,
      except for mental health; and they scored significantly worse on depression,
      fatigue, problems with sleep, and symptom severity. Patients with neuropathic
      symptoms and those taking high levels of steroids had significantly impaired
      scores on some of the relevant measures. There were no significant correlations
      between the modified BVDI scores with the SF-36 subscales or with the other self
      report disease-related measures. The HAQ showed high internal consistency and
      high concurrent and discriminant validity. CONCLUSION: Many aspects of QOL are
      significantly impaired in PSV. Self-reported pain and disease symptoms, SF-36
      scores, and depression and anxiety levels are significant indicators of the
      adverse impact of vasculitis on patients' lives that need to be assessed and
      managed.

PMID- 14673971
TI  - Factors contributing to possession and use of walking aids among persons with
      rheumatoid arthritis and osteoarthritis.
AB  - OBJECTIVE: To investigate the possession and use of walking aids among patients
      with rheumatoid arthritis (RA) or osteoarthritis (OA), and to identify factors
      contributing to possession and actual use of these aids. METHODS: A random sample
      of 640 patients with RA or OA was derived from a database of 6,500 registered
      patients. A total of 410 (64%) patients (223 RA, 187 OA) completed a
      questionnaire on possession and use of walking aids. Demographics, disease
      related characteristics, and information about possession and use were assessed.
      Logistic regression analyses were used to determine which factors are associated
      with the possession and use of walking aids. RESULTS: Forty-nine percent of the
      RA patients and 44% of the OA patients owned a walking aid. Canes, forearm
      crutches, walkers, and orthopedic footwear were most frequently possessed. In the
      RA group, age, education, frequency of pain, and disability were associated with
      possessing a walking aid. In the OA group, age and disability were associated
      with possession. Approximately 30% of the owners did not use their walking aid.
      Factors associated with the actual use of an aid included higher age, a high
      intensity of pain, more disability, decrease in morning stiffness by the aid, and
      a positive evaluation of the aid. CONCLUSION: Almost half of patients with RA or
      OA possess a walking aid. Disability, pain, and age-related impairments seem to
      determine the need for a walking aid. Nonuse is associated with less need,
      negative outcome, and negative evaluation of the walking aid.

PMID- 14673972
TI  - Hepatitis C and methotrexate.

PMID- 14673973
TI  - Young women with chronic disease: a female perspective on the impact and
      management of rheumatoid arthritis.

PMID- 14673974
TI  - Good days and bad days: innovation in capturing data about the functional status
      of our patients.

PMID- 14673975
TI  - Concomitant giant cell aortitis, thoracic aortic aneurysm, and aortic arch
      syndrome: occurrence in a patient and significance.

PMID- 14673976
TI  - Thrombosis and pediatric Wegener's granulomatosis: acquired and genetic risk
      factors for hypercoagulability.

PMID- 14673977
TI  - Potential role of mitral valve strands on stroke recurrence in rheumatoid
      arthritis.

PMID- 14673978
TI  - Ocular involvements of Japanese patients with giant cell arteritis from the first
      nation-wide survey.

PMID- 14673980
TI  - Oncostatin M: foe or friend?

PMID- 14673981
TI  - The usual suspects: verdict not guilty?

PMID- 14673982
TI  - Rheumatoid arthritis therapy after tumor necrosis factor and interleukin-1
      blockade.

PMID- 14673983
TI  - Catastrophic antiphospholipid syndrome: where do we stand?

PMID- 14673984
TI  - Efficacy and safety of tacrolimus in patients with rheumatoid arthritis: a double
      blind trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of tacrolimus as monotherapy in
      controlling the signs and symptoms of patients with rheumatoid arthritis (RA).
      METHODS: This was a 6-month, phase III, double-blind, multicenter study. Patients
      with active RA who had discontinued all disease-modifying antirheumatic drugs
      (DMARDs) for an appropriate washout period (at least 1 month) and who, after the
      washout period, had a stable joint count (at least 10 tender/painful joints and 7
      swollen joints) were stratified according to DMARD intolerance or DMARD
      resistance, and randomized to receive a single daily oral dose of placebo,
      tacrolimus 2 mg, or tacrolimus 3 mg. RESULTS: A total of 464 patients received at
      least 1 dose of study drug. Baseline characteristics were similar among the 3
      treatment groups. American College of Rheumatology 20% improvement (ACR20)
      success (defined as completion of 6 months of treatment and an ACR20 response at
      the month 6 visit) for the placebo, tacrolimus 2 mg, and tacrolimus 3 mg groups
      was 10.2%, 18.8% (P < 0.05 versus placebo), and 26.8% (P < 0.0005 versus
      placebo), respectively. At the end of treatment, the ACR20 and ACR50 response
      rates in the 3-mg group were 32.0% (P < 0.005 versus placebo) and 11.8% (P < 0.05
      versus placebo), respectively. DMARD-intolerant patients had better ACR response
      rates than did DMARD-resistant patients. Although serum creatinine levels
      increased by >/=40% from baseline at some time during the trial in 20% and 29% of
      patients receiving tacrolimus 2 mg/day and 3 mg/day, respectively, the serum
      creatinine level remained within the normal range throughout the trial in
      approximately 90% of patients. CONCLUSION: Tacrolimus, at dosages of both 2
      mg/day and 3 mg/day, is efficacious and safe as monotherapy for patients with
      active RA, but treatment with the 3-mg dose of tacrolimus resulted in generally
      better ACR response rates.

PMID- 14673985
TI  - Rheumatoid arthritis of the shoulder joint: comparison of conventional
      radiography, ultrasound, and dynamic contrast-enhanced magnetic resonance
      imaging.
AB  - OBJECTIVE: To determine the role of ultrasound and magnetic resonance imaging
      (MRI) compared with conventional radiography in the detection of chronic and
      acute inflammatory manifestations of rheumatoid arthritis (RA) of the shoulder
      joint. METHODS: Forty-three consecutive patients with known RA prospectively
      underwent clinical examination, radiography, ultrasound, and MRI of the shoulder
      joints. Each patient was assigned a clinical/laboratory score consisting of 7
      parameters, including measurements of shoulder mobility, the erythrocyte
      sedimentation rate, and C-reactive protein level. Conventional radiography was
      standardized and performed in 2 planes. Ultrasound was performed in 10 predefined
      planes using a 7.5-MHz linear transducer. MRI at 1.5T comprised transverse and
      oblique coronal T1- and T2*-weighted fast spin-echo, gradient-echo (GRE), and
      inversion-recovery sequences with a matrix size of up to 512 pixels. A dynamic T1
      weighted GRE sequence was acquired with intravenous administration of contrast
      medium. Erosions were assessed using all 3 imaging techniques on a 4-point scale.
      Soft-tissue involvement was evaluated according to the presence of synovitis,
      tenosynovitis, and bursitis on ultrasound and MRI. The results in the study group
      were compared with those obtained in a control group of 10 patients with shoulder
      pain. RESULTS: In the study group, erosions of the humeroscapular joint were
      detected by conventional radiography in 26 patients, by ultrasound in 30
      patients, and by MRI in 39 patients; the differences were statistically
      significant for the comparisons of conventional radiography with MRI and for
      ultrasound versus MRI (P < 0.0001). Conventional radiography detected 12 erosions
      of the scapula and MRI detected 15. Synovitis was demonstrated in 12 patients by
      ultrasound and in 27 patients by MRI (P = 0.0003). Tenosynovitis was observed in
      15 patients by ultrasound and in 28 patients by MRI (P = 0.0064). Bursitis was
      detected in 13 patients by ultrasound and in 18 patients by MRI. The findings on
      dynamic contrast-enhanced MRI correlated significantly with the detection of
      synovitis by ultrasound and erosions by static MRI (P < 0.05). CONCLUSION:
      Ultrasound and MRI supplement conventional radiography in assessing the shoulder
      joint. Although conventional radiography can be used as the sole method of
      following up known joint destruction in RA, ultrasound and, preferably, MRI are
      recommended as additional techniques in the initial diagnostic evaluation when
      radiography yields negative results.

PMID- 14673986
TI  - Suppression of osteoclastogenesis in rheumatoid arthritis by induction of
      apoptosis in activated CD4+ T cells.
AB  - OBJECTIVE: To examine the suppressive effect of anti-human Fas monoclonal
      antibody (mAb) on osteoclastogenesis in rheumatoid arthritis (RA) both in vitro
      and in vivo. METHODS: For in vitro analysis, activated CD4+ T cells derived from
      peripheral blood mononuclear cells were left untreated or were treated with
      humanized anti-human Fas mAb (R-125224) and cocultured with human monocytes. On
      day 12, the number of tartrate-resistant acid phosphatase (TRAP)-positive
      multinucleated cells was counted. For in vivo analysis, tissue derived from human
      RA pannus was implanted with a slice of dentin subcutaneously in the backs of
      SCID mice (SCID-HuRAg-pit model). R-125224 was administered intravenously once a
      week for 3 weeks. The implanted tissue and dentin slice were removed, and the
      pits formed on the dentin slice were analyzed. RESULTS: In vitro, coculture of
      activated CD4+ T cells and peripheral monocytes induced osteoclastogenesis. The
      number of TRAP-positive multinucleated cells was reduced when activated CD4+ T
      cells were treated with R-125224. We established a new animal model for
      monitoring osteoclastogenesis, SCID-HuRAg-pit. We found that with R-125224
      treatment, the number of pits formed on the implanted dentin slices was
      significantly reduced and the number of lymphocytes in the implanted RA synovial
      tissue was dramatically reduced in this model. CONCLUSION: This is the first
      study to demonstrate the suppressive effect of anti-human Fas mAb on
      osteoclastogenesis in RA synovial tissues through the induction of T cell
      apoptosis. Induction of apoptosis of infiltrated lymphocytes could be a useful
      therapeutic strategy for RA, in terms of suppressing both inflammation and bone
      destruction.

PMID- 14673987
TI  - Physical functioning over three years in knee osteoarthritis: role of
      psychosocial, local mechanical, and neuromuscular factors.
AB  - OBJECTIVE: To identify factors that predict a poor physical function outcome over
      3 years in individuals with knee osteoarthritis (OA), in an effort to aid in the
      development of strategies to prevent such functional limitations and
      consequential disability. METHODS: Community-recruited individuals with knee OA
      underwent baseline, 18-month, and 3-year assessments of candidate risk factors
      and physical function. Risk factors were age, body mass index (BMI), knee pain
      intensity (on a visual analog scale [VAS]), local mechanical and neuromuscular
      factors (varus-valgus laxity, malalignment, proprioceptive inaccuracy, quadriceps
      strength, hamstring strength), activity level (Physical Activity Scale for the
      Elderly, amount of aerobic exercise), and psychosocial factors (Short-Form 36 [SF
      36] mental health and role-functioning emotional subscales, self-efficacy using
      the Arthritis Self-Efficacy Scale physical function subscale, and social support
      using the Medical Outcomes Study Social Support Survey). Outcome was assessed
      using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
      physical function scale and rate of chair-stand performance. Participants were
      grouped by quintile of baseline WOMAC score. The baseline to 3-year outcome was
      considered "good" when function improved by 1 or more quintiles or remained
      within the 2 highest function groups, and was considered "poor" when function
      declined by 1 or more quintiles or remained within the 3 lowest function groups.
      The same approach was taken for chair-stand outcome. Logistic regression was used
      to evaluate both the baseline level and the baseline to 18-month change in each
      factor as a predictor of physical function outcome over 3 years, adjusting for
      age, BMI, knee pain intensity, disease severity, and additional potential
      confounders. RESULTS: Factors that significantly increased the likelihood of a
      poor WOMAC outcome were baseline laxity (crude odds ratio [OR] 1.48/3 degrees,
      95% confidence interval [95% CI] 1.02-2.14), BMI (OR 1.26/5 units, 95% CI 1.01
      1.57), knee pain intensity (OR 1.21/20 mm on VAS, 95% CI 1.00-1.47), and baseline
      to 18-month increase in knee pain (OR 1.32/20 mm on VAS, 95% CI 1.06-1.65).
      Factors that significantly protected against a poor WOMAC outcome were better
      baseline mental health (OR 0.62/5 points, 95% CI 0.44-0.87), self-efficacy (OR
      0.79/5 points, 95% CI 0.67-0.93), and social support (OR 0.86/10 points, 95% CI
      0.75-0.98), and greater amount of aerobic exercise (OR 0.75/60 minutes each week,
      95% CI 0.63-0.89). Factors that increased the likelihood for a poor function
      outcome by the chair-stand performance rate were age and proprioceptive
      inaccuracy, and factors that reduced the likelihood for poor chair-stand outcome
      were strength (attenuated after adjusting for pain intensity or self-efficacy),
      self-efficacy, and aerobic exercise. Individuals who sustained high function and
      those who sustained low function over the 3 years were described. CONCLUSION:
      Factors placing individuals with knee OA at greater risk of a poor function
      outcome by at least 1 of the 2 function measures included the local factors
      laxity and proprioceptive inaccuracy, as well as age, BMI, and knee pain
      intensity. Factors protecting against a poor function outcome included strength,
      the psychosocial factors mental health, self-efficacy, and social support, and
      the activity level measured by the amount of aerobic exercise per week. The
      identification of these factors provides possible targets for rehabilitative and
      self-management strategies to prevent disability.

PMID- 14673988
TI  - Patterns of interphalangeal hand joint involvement of osteoarthritis among men
      and women: a British cohort study.
AB  - OBJECTIVE: To characterize the pattern of involvement of osteoarthritis (OA) of
      the hand among men and women of the same age. METHODS: Structured hand
      examinations were performed on 1,467 men and 1,519 women who were age 53 years
      and born in England, Scotland, or Wales during the first week of March 1946
      (identified through the United Kingdom National Survey of Health and
      Development). OA at each joint site was characterized using a previously
      validated examination schedule. The interrelationship of involvement of different
      hand joints was analyzed by logistic regression and cluster analyses. RESULTS:
      There was clear evidence of polyarticular involvement in the hand joints of both
      the men and the women. Among the women, 161 subjects had >/=4 joints involved,
      compared with only 41 subjects expected in this category (P < 0.001). Among the
      men, 87 subjects were observed to have >/=4 joints involved, in contrast with
      only 7 subjects expected (P < 0.001). The pattern of hand joint involvement
      (characterized by clustering primarily by row and symmetric joint involvement,
      rather than clustering by ray) was found to be almost identical between the men
      and the women. CONCLUSION: This study confirms the existence of a polyarticular
      subset of OA among men that has characteristics similar to those of the variant
      observed among women. The data suggest that the genetic or metabolic influences
      underlying this particular variant of OA acts similarly in both sexes.

PMID- 14673989
TI  - Longitudinal analysis of cartilage atrophy in the knees of patients with spinal
      cord injury.
AB  - OBJECTIVE: A previous cross-sectional study indicated that the morphology of
      patellar and tibial cartilage is subject to change after spinal cord injury
      (SCI). The aim of this study was to perform a longitudinal analysis of cartilage
      atrophy in all knee compartments, including the femoral condyles, in SCI patients
      over 12 months. METHODS: The right knees of 9 patients with complete, traumatic
      SCI were examined shortly after the injury (mean +/- SD 9 +/- 4 weeks) and at 6
      and 12 months postinjury. Three-dimensional morphology of the patellar, tibial,
      and femoral cartilage (mean and maximum thickness, volume, and surface area) was
      determined from coronal and transversal magnetic resonance images (fat-suppressed
      gradient-echo sequences) using validated postprocessing techniques. RESULTS: The
      mean thickness of knee joint cartilage decreased significantly during the first 6
      months after injury (range 5-7%; P < 0.05). The mean change at 12 months was 9%
      in the patella, 11% in the medial tibia, 11% in the medial femoral condyle, 13%
      in the lateral tibia, and 10% in the lateral femoral condyle (P < 0.05 for all
      compartments). CONCLUSION: This is the first report of a longitudinal analysis of
      cartilage atrophy in patients with SCI. These data show that human cartilage
      atrophies in the absence of normal joint loading and movement after SCI, with a
      rate of change that is higher than that observed in osteoarthritis (OA). A
      potential clinical implication is that cartilage thinning after SCI may affect
      the stress distribution in the joint and render it vulnerable to OA. Future
      studies should focus on whether specific exercise protocols and rehabilitation
      programs can prevent cartilage thinning.

PMID- 14673990
TI  - Indentation testing of human cartilage: sensitivity to articular surface
      degeneration.
AB  - OBJECTIVE: To determine, for clinical indentation testing of human articular
      cartilage, the effects of aging and degeneration on indentation stiffness and
      traditional indices of cartilage degeneration; the relationship between
      indentation stiffness and indices of degeneration; and the sensitivity and
      specificity of indentation stiffness to cartilage degeneration. METHODS:
      Osteochondral cores from femoral condyles of cadaveric human donors were
      harvested. Samples were distributed into experimental groups based on donor age
      (young [20-39 years], middle [40-59 years], and old [>/=60 years]), and a
      macroscopic articular surface appearance that was either normal or mildly
      degenerate, without deep erosion. Samples were analyzed for indentation
      stiffness, cartilage thickness, India ink staining (quantitated as the reflected
      light score), and Mankin-Shapiro histopathology score. RESULTS: Indentation
      stiffness, India ink staining, and the histopathology score each varied markedly
      between normal-sample and degenerate-sample groups but varied relatively little
      between normal samples obtained from different age groups. A decrease in
      indentation stiffness (softening) correlated with a decrease in the reflectance
      score and an increase in the overall histopathology score, especially the surface
      irregularity component of the histopathology score. Receiver operating
      characteristic analysis suggested that the indentation testing could accurately
      detect cartilage degeneration as indicated by macroscopic appearance, India ink
      staining, and histopathology score. CONCLUSION: The indentation stiffness of the
      normal to mildly degenerate samples tested in this study was sensitive to mild
      degeneration at the articular surface and was insensitive to changes associated
      with normal aging or to slight variations in cartilage thickness. This suggests
      that indentation testing may be a useful clinical tool for the evaluation of
      early-stage degenerative changes in articular cartilage.

PMID- 14673991
TI  - Molecular phenotyping of human chondrocyte cell lines T/C-28a2, T/C-28a4, and C
      28/I2.
AB  - OBJECTIVE: Because the immortalized chondrocyte cell lines C-28/I2, T/C-28a2, and
      T/C-28a4 have become a common tool in cartilage research, permitting
      investigations in a largely unlimited and standardized manner, we investigated
      the molecular phenotype of these cell lines by gene expression profiling.
      METHODS: Complementary DNA-array analysis as well as online quantitative
      polymerase chain reaction were used to identify the gene expression profiles of
      the 3 cell lines cultured in monolayer and alginate beads, as compared with the
      expression profiles of cultured human adult primary chondrocytes. RESULTS: A
      similar, but not identical, gene expression profile was established for all 3
      cell lines. SOX9 was expressed at a significant level in all 3 cell lines.
      Extracellular matrix proteins and matrix-degrading proteases were rarely
      expressed. In contrast, genes involved in the cell cycle were strongly up
      regulated, as compared with the expression levels in physiologic chondrocytes.
      CONCLUSION: The expression of SOX9, the master gene of chondrocytic cell
      differentiation, reflects the basically chondrocytic phenotype of these cells.
      However, the major issue appears to be that these cell lines mainly proliferate
      and show less expression of genes involved in matrix synthesis and turnover. In
      this respect, C-28/I2 cells display the highest levels of matrix-anabolic and
      matrix-catabolic genes and thus are presumably preferable for use in
      investigating chondrocyte anabolic and catabolic activity and its regulation.
      None of the 3 cell lines appears to be a direct substitute for primary
      chondrocytes. A successful approach will have to validate the findings obtained
      with chondrocyte cell lines by using primary chondrocytes or cartilage-tissue
      cultures. This would permit the establishment of reproducible in vitro models and
      subsequently allow investigators to relate the findings to the physiologic
      situation.

PMID- 14673992
TI  - Oncostatin M in combination with tumor necrosis factor alpha induces cartilage
      damage and matrix metalloproteinase expression in vitro and in vivo.
AB  - OBJECTIVE: To determine the effects of the proinflammatory cytokine combination
      of oncostatin M (OSM) and tumor necrosis factor alpha (TNFalpha) on cartilage
      destruction in both in vitro and in vivo model systems. METHODS: The release of
      collagen and proteoglycan was assessed in bovine cartilage explant cultures,
      while messenger RNA (mRNA) from bovine chondrocytes was analyzed by Northern
      blotting. Immunohistochemistry was performed on sections prepared from murine
      joints following injection of adenovirus vectors encoding murine OSM and/or
      murine TNFalpha. RESULTS: The combination of OSM + TNFalpha induced significant
      collagen release from bovine cartilage, accompanied by high levels of active
      collagenolytic activity. Northern blot analysis indicated that this cytokine
      combination synergistically induced matrix metalloproteinase 1 (MMP-1), MMP-3,
      and MMP-13 mRNA. The in vivo data clearly indicated that OSM + TNFalpha
      overexpression increased MMP levels and decreased levels of tissue inhibitor of
      metalloproteinases 1 (TIMP-1). Specifically, OSM + TNFalpha induced marked
      synovial hyperplasia, inflammation, and cartilage and bone destruction with a
      concomitant increase in MMP expression in both cartilage and synovium and
      decreased TIMP-1 expression in the articular cartilage. These effects were
      markedly greater than those seen with either cytokine alone. CONCLUSION: This
      study demonstrates that OSM + TNFalpha represents a potent proinflammatory
      cytokine combination that markedly induces MMP production in both cartilage and
      synovium, thus promoting joint destruction.

PMID- 14673993
TI  - Increased oxidative stress with aging reduces chondrocyte survival: correlation
      with intracellular glutathione levels.
AB  - OBJECTIVE: To examine the role of oxidative stress in mediating cell death in
      chondrocytes isolated from the articular cartilage of young and old adult human
      tissue donors. METHODS: Cell death induced by the oxidant SIN-1 was evaluated in
      the alginate bead culture system using fluorescent probes to assess membrane
      integrity. Generation of peroxynitrite by the decomposition of SIN-1 was
      confirmed by positive immunostaining of treated cells for 3-nitrotyrosine.
      Determinations of oxidized glutathione (GSSG) and reduced glutathione (GSH) were
      performed in monolayer cultures using an enzyme- recycling assay. Cells were
      depleted of intracellular glutathione either by the addition of DL-buthionine
      (S,R)-sulfoximine or by removal of L-cystine from the culture media. The activity
      of cellular antioxidant enzymes was determined spectrophotometrically by the
      decay of substrate from the reaction mixture. RESULTS: More chondrocytes (>2
      fold) from old donors (>/=50 years) died after exposure to 1 mM SIN-1 relative to
      those derived from young donors (18-49 years). Although autocrine production of
      insulin-like growth factor 1 (IGF-1) promotes chondrocyte survival, pretreatment
      with IGF-1 could not prevent the cell death induced by SIN-1 exposure. Cells
      isolated from old donors had a higher ratio of GSSG to GSH. Glutathione reductase
      is the principal enzyme involved in the regeneration of GSH from GSSG. Treatment
      of chondrocytes with SIN-1 to induce oxidative stress in vitro resulted in the
      decreased activity of glutathione reductase and thioredoxin reductase, but not
      catalase. Cells depleted of intracellular glutathione were more susceptible to
      cell death induced by SIN-1. CONCLUSION: These results provide evidence that
      increased oxidative stress with aging makes chondrocytes more susceptible to
      oxidant-mediated cell death through the dysregulation of the glutathione
      antioxidant system. This may represent an important contributing factor to the
      development of osteoarthritis in older adults.

PMID- 14673994
TI  - G1 domain of aggrecan cointernalizes with hyaluronan via a CD44-mediated
      mechanism in bovine articular chondrocytes.
AB  - OBJECTIVE: To determine whether aggrecan fragments bound to hyaluronan (HA) can
      be retained and internalized by articular chondrocytes and whether these events
      are dependent on HA and its receptor, CD44. An additional objective was to
      determine whether partial degradation of aggrecan is a prerequisite for
      internalization. METHODS: Binding and internalization of a variety of fluorescein
      isothiocyanate (FITC)- or biotin-labeled HA/proteoglycan probes were investigated
      on normal bovine articular cartilage chondrocytes, bovine articular chondrocytes
      transfected with a dominant-negative construct of CD44, or COS-7 cells
      transfected with wild-type CD44. The probes were defined as being internalized by
      the presence of label associated with the cells following extensive
      trypsinization of the cell surface. RESULTS: Biotinylated aggrecan fragments
      bound to FITC-HA were cointernalized in bovine articular chondrocytes or COS-7
      cells transfected with CD44. Intracellular vesicles containing FITC-HA
      colocalized with a fluorescent probe for lysosomes. The internalization of the
      aggrecan fragments was dependent on the presence of HA as well as the presence of
      functional CD44. Intact aggrecan/FITC-HA complexes bound to the cell surface but
      were not internalized. However, following brief trypsin digestion of the
      aggrecan/HA complex, the remaining proteoglycan fragments were bound and
      internalized. CONCLUSION: Partially degraded aggrecan fragments (e.g., aggrecan
      G1 domains bound to HA) can be internalized by articular chondrocytes via a
      mechanism involving HA/CD44-mediated endocytosis. Further, the presence of an
      intact aggrecan monomer bound to HA inhibits the internalization of HA as well as
      HA-bound fragments.

PMID- 14673995
TI  - Reduction of osteophyte formation and synovial thickening by adenoviral
      overexpression of transforming growth factor beta/bone morphogenetic protein
      inhibitors during experimental osteoarthritis.
AB  - OBJECTIVE: Osteoarthritis (OA) is a joint disease characterized by osteophyte
      development, fibrosis, and articular cartilage damage. Effects of exogenous
      transforming growth factor beta (TGFbeta) isoforms and bone morphogenetic
      proteins (BMPs) suggest a role for these growth factors in the pathogenesis of
      OA. The aim of this study was to elucidate the role of endogenous TGFbeta and BMP
      during papain-induced OA-like changes in mice. METHODS: We used adenoviral
      overexpression of TGFbeta and BMP antagonists to block growth factor signaling.
      An adenovirus expressing a secreted, pan-specific TGFbeta antagonist called
      murine latency-associated peptide 1 (mLAP-1) was used. In addition, we used
      intracellular inhibitory Smad6 as a BMP antagonist and Smad7 as a TGFbeta/BMP
      inhibitor. Papain was injected into the knee joints of C57BL/6 mice to induce
      osteophyte development, synovial thickening, and articular cartilage proteoglycan
      (PG) loss. RESULTS: Intraarticular injection of papain caused increased protein
      expression of several TGFbeta and BMP isoforms in synovium and cartilage.
      Adenovirus transfection into the joint resulted in a strong expression of the
      transgenes in the synovial lining. Overexpression of mLAP-1, Smad6, and Smad7 led
      to a significant reduction in osteophyte formation compared with that in
      controls. Smad6 and Smad7 overexpression also significantly decreased synovial
      thickening. Furthermore, the secreted TGFbeta inhibitor mLAP-1 increased
      articular cartilage PG loss. CONCLUSION: Our results indicate a pivotal role of
      endogenous TGFbeta in the development of osteophytes and synovial thickening,
      implicating endogenous TGFbeta in the pathogenesis of OA. In contrast, the
      prevention of cartilage damage by endogenous TGFbeta signifies the protective
      role of TGFbeta in articular cartilage. This is the first study to demonstrate
      that endogenous BMPs are involved in osteophyte formation and synovial thickening
      in experimental OA.

PMID- 14673996
TI  - Gene deletion of either interleukin-1beta, interleukin-1beta-converting enzyme,
      inducible nitric oxide synthase, or stromelysin 1 accelerates the development of
      knee osteoarthritis in mice after surgical transection of the medial collateral
      ligament and partial medial meniscectomy.
AB  - OBJECTIVE: To investigate the development of osteoarthritis (OA) after
      transection of the medial collateral ligament and partial medial meniscectomy in
      mice in which genes encoding either interleukin-1beta (IL-1beta), IL-1beta
      converting enzyme (ICE), stromelysin 1, or inducible nitric oxide synthase (iNOS)
      were deleted. METHODS: Sectioning of the medial collateral ligament and partial
      medial meniscectomy were performed on right knee joints of wild-type and knockout
      mice. Left joints served as unoperated controls. Serial histologic sections were
      obtained from throughout the whole joint of both knees 4 days or 1, 2, 3, or 4
      weeks after surgery. Sections were graded for OA lesions on a scale of 0-6 and
      were assessed for breakdown of tibial cartilage matrix proteoglycan (aggrecan)
      and type II collagen by matrix metalloproteinases (MMPs) and aggrecanases with
      immunohistochemistry studies using anti-VDIPEN, anti-NITEGE, and Col2-3/4C(short)
      neoepitope antibodies. Proteoglycan depletion was assessed by Alcian blue
      staining and chondrocyte cell death, with the TUNEL technique. RESULTS: All
      knockout mice showed accelerated development of OA lesions in the medial tibial
      cartilage after surgery, compared with wild-type mice. ICE-, iNOS-, and
      particularly IL-1beta-knockout mice developed OA lesions in the lateral cartilage
      of unoperated limbs. Development of focal histopathologic lesions was accompanied
      by increased levels of MMP-, aggrecanase-, and collagenase-generated cleavage
      neoepitopes in areas around lesions, while nonlesional areas showed no change in
      immunostaining. Extensive cell death was also detected by TUNEL staining in focal
      areas around lesions. CONCLUSION: We postulate that deletion of each of these
      genes, which encode molecules capable of producing degenerative changes in
      cartilage, leads to changes in the homeostatic controls regulating the balance
      between anabolism and catabolism, favoring accelerated cartilage degeneration.
      These observations suggest that these genes may play important regulatory roles
      in maintaining normal homeostasis in articular cartilage matrix turnover.

PMID- 14673997
TI  - Stem cell therapy in a caprine model of osteoarthritis.
AB  - OBJECTIVE: To explore the role that implanted mesenchymal stem cells may play in
      tissue repair or regeneration of the injured joint, by delivery of an autologous
      preparation of stem cells to caprine knee joints following induction of
      osteoarthritis (OA). METHODS: Adult stem cells were isolated from caprine bone
      marrow, expanded in culture, and transduced to express green fluorescent protein.
      OA was induced unilaterally in the knee joint of donor animals by complete
      excision of the medial meniscus and resection of the anterior cruciate ligament.
      After 6 weeks, a single dose of 10 million autologous cells suspended in a dilute
      solution of sodium hyaluronan was delivered to the injured knee by direct
      intraarticular injection. Control animals received sodium hyaluronan alone.
      RESULTS: In cell-treated joints, there was evidence of marked regeneration of the
      medial meniscus, and implanted cells were detected in the newly formed tissue.
      Degeneration of the articular cartilage, osteophytic remodeling, and subchondral
      sclerosis were reduced in cell-treated joints compared with joints treated with
      vehicle alone without cells. There was no evidence of repair of the ligament in
      any of the joints. CONCLUSION: Local delivery of adult mesenchymal stem cells to
      injured joints stimulates regeneration of meniscal tissue and retards the
      progressive destruction normally seen in this model of OA.

PMID- 14673998
TI  - B lymphocyte stimulator overexpression in patients with systemic lupus
      erythematosus: longitudinal observations.
AB  - OBJECTIVE: To assess the overexpression of B lymphocyte stimulator (BLyS) over
      time in patients with systemic lupus erythematosus (SLE). METHODS: Sixty-eight
      SLE patients were followed up longitudinally for a median 369 days. At each
      physician encounter, disease activity was assessed by the Systemic Lupus
      Erythematosus Disease Activity Index, and blood was collected for determination
      of the serum BLyS level, blood BLyS messenger RNA (mRNA) level, and cell surface
      BLyS expression. Twenty normal control subjects underwent similar laboratory
      evaluations. RESULTS: In contrast to the uniformly normal serum BLyS and blood
      BLyS mRNA phenotypes in control subjects, SLE patients displayed marked
      heterogeneity, with 50% and 61% of patients manifesting persistently or
      intermittently elevated serum BLyS and blood BLyS mRNA phenotypes, respectively.
      Surface BLyS expression by SLE peripheral blood mononuclear cells was also often
      increased. Treatment of patients who had elevated serum BLyS levels with
      intensive courses of high-dose corticosteroids resulted in marked reductions in
      serum BLyS levels, and tapering of the corticosteroid dosage often resulted in
      increases in serum BLyS levels. Serum BLyS levels generally correlated with anti
      double-stranded DNA (anti-dsDNA) titers (in those with detectable anti-dsDNA
      titers), but changes in serum BLyS levels did not correlate with changes in
      disease activity in individual patients. Serum BLyS phenotype did not associate
      with specific organ system involvement. CONCLUSION: Dysregulation of BLyS over
      extended periods of time is common in patients with SLE. Neutralization of BLyS
      activity with an appropriate BLyS antagonist may be therapeutically beneficial.

PMID- 14673999
TI  - Roles of CCR2 and CXCR3 in the T cell-mediated response occurring during lupus
      flares.
AB  - OBJECTIVE: Infiltrating lymphocytes have been demonstrated to play an important
      role in the tissue injury that occurs in systemic lupus erythematosus (SLE).
      Inflammatory chemokines control lymphocyte traffic through their interaction with
      T cell chemokine receptors. In this study we assessed the expression of chemokine
      receptors on T cell subsets of patients with active or inactive SLE. METHODS:
      Forty-four SLE patients (40 women and 4 men) were included in the study. The
      patients were divided according to their SLE Disease Activity Index (SLEDAI),
      which resulted in a group of patients with inactive SLE (n = 27) and a group with
      active SLE (n = 17). The control group was composed of 22 healthy blood donors. A
      disease control group consisted of 18 patients infected with human
      immunodeficiency virus. Expression of chemokine receptors CCR1, CCR2, CCR5,
      CXCR3, CXCR4, and CX3CR1 was assessed on whole blood samples by
      immunofluorescence analysis. RESULTS: On T lymphocytes, significant differences
      between the SLE patients and controls were observed only in the expression of
      CCR2 and CXCR3. On monocytes, no significant differences in CCR2 expression were
      observed between the healthy controls and the SLE patients. The proportion of
      CD8+,CCR2+ T cells was significantly lower in the SLE patients compared with the
      controls (mean +/- SD 2.3 +/- 1.3% and 3.5 +/- 3.2% in the active and inactive
      SLE groups, respectively, versus 21 +/- 24% in controls; P < 0.0001 for both).
      The CD4+,CCR2+ subset was represented similarly among the controls and patients
      with inactive SLE (16.7 +/- 5.8% and 12.8 +/- 8.1%, respectively) but was
      depleted in patients with active SLE (7.1 +/- 4.4%; P < 0.0001 versus controls).
      The active SLE group expressed significantly lower circulating levels of
      CD4+,CCR2+ T cells than did the inactive disease group (P = 0.007). A negative
      correlation was found between the proportion of CD4+,CCR2+ T cells and the SLEDAI
      (r = -0.43, P = 0.005, by Spearman's correlation). Proportions of CD8+,CXCR3+ T
      cells were similar between the SLE groups and the control group (58 +/- 22.6% in
      active SLE, 47.1 +/- 20% in inactive SLE, and 59.4 +/- 17.3% in controls). The
      proportion of CXCR3-expressing CD4+ T cells was decreased in the active disease
      group (23.5 +/- 3.2% versus 39.9 +/- 12.5% in controls; P = 0.008) but not in the
      inactive disease group (34.8 +/- 9.5%). A trend toward a significant negative
      correlation was observed between the decreased proportion of CD4+,CXCR3+ T cells
      and the SLEDAI (P = 0.08). Following in vitro activation of purified CD4 T cells,
      only CCR2 was internalized, whereas expression of CXCR3 was retained in activated
      CD4 cells. CONCLUSION: The numbers of circulating CD4+,CXCR3+ and CD4+,CCR2+ T
      cells are selectively decreased during SLE flares. A decrease in the number of
      circulating CD4+ T cells expressing CCR2 and/or CXCR3 could serve as a biomarker
      of the SLE flare.

PMID- 14674000
TI  - Intravenous immunoglobulin abrogates dendritic cell differentiation induced by
      interferon-alpha present in serum from patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: Alterations in the function of dendritic cells (DCs) may explain the
      systemic autoimmune responses that characterize systemic lupus erythematosus
      (SLE). Even though several reports have documented the beneficial effect of
      intravenous immunoglobulin (IVIG) in SLE, the underlying mechanisms of action
      remain poorly understood. Considering the effect of serum factors, including
      interferon-alpha (IFNalpha), on the activity of DCs, we investigated the effects
      of IVIG on the differentiation of DCs mediated by serum from SLE patients.
      METHODS: DCs were differentiated from peripheral blood monocytes obtained from
      SLE patients and from healthy blood donors, in the presence of SLE serum. IVIG
      was used at a concentration of 0.15 mM. A functional assay was performed to
      assess the inhibitory effect of IVIG on the uptake of nucleosomes by DCs.
      RESULTS: IVIG interfered with the differentiation of DCs from SLE patients and
      healthy donors cultured in the presence of SLE serum. Treatment of DCs with IVIG
      inhibited the ingestion of nucleosomes by immature DCs, by up to 36%. CONCLUSION:
      The present findings indicate that IVIG, by down-regulating the IFNalpha-mediated
      differentiation of DCs and by inhibiting uptake of nucleosomes, may exert an
      essential immunoregulatory effect in SLE patients at the onset of the immune
      response, at the DC level. Given the critical role of HLA molecules and the
      costimulatory signals delivered by CD80 and CD86 in optimal antigen presentation
      and T cell activation, inhibition of expression of HLA and CD80/CD86 on DCs by
      IVIG offers a plausible explanation for the efficacy of IVIG in SLE and other
      immune-mediated inflammatory conditions.

PMID- 14674001
TI  - N-terminal pro-brain natriuretic peptide as a diagnostic marker of early
      pulmonary artery hypertension in patients with systemic sclerosis and effects of
      calcium-channel blockers.
AB  - OBJECTIVE: To evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP) as a
      marker of early pulmonary artery hypertension (PAH) and to study changes in the
      levels of this marker following treatment with dihydropyridine-type calcium
      channel blocker (DTCCB) in patients with systemic sclerosis (SSc). METHODS: We
      evaluated 40 consecutive SSc patients who had been hospitalized for followup care
      (mean +/- SD age 56 +/- 11 years and mean +/- SD duration of cutaneous disease 9
      +/- 9 years; 27 with limited cutaneous and 13 with diffuse cutaneous disease) but
      who had no clinical symptoms of heart failure and had a normal left ventricular
      ejection fraction. At baseline, 10 patients had PAH, defined as a systolic
      pulmonary artery pressure (sPAP) >40 mm Hg, as measured by echocardiography.
      Levels of NT-proBNP were determined at baseline (after discontinuation of DTCCB
      treatment for 72 hours), after taking 3 doses of DTCCB following treatment
      reinitiation (assessment 1), and after 6-9 months of continuous DTCCB treatment
      (assessment 2) in the 20 patients who attended regular appointments (including
      the 10 patients with PAH at baseline). RESULTS: At baseline, 13 patients had high
      NT-proBNP values for their ages. High NT-proBNP levels identified patients with
      PAH with a sensitivity of 90%, a specificity of 90.3%, a positive predictive
      value of 69.2%, and a negative predictive value of 96%. The NT-proBNP level
      correlated with the sPAP (r = 0.44; P = 0.006). By assessment 1, the number of
      patients with PAH and high levels of NT-proBNP had decreased from 9 of 10 to 2 of
      10 (P = 0.02). This decrease was partially sustained at assessment 2 (4 of 10
      patients; P = 0.06). CONCLUSION: NT-proBNP is a useful biologic marker that can
      be used to diagnose early PAH in SSc patients without clinical heart failure.
      Measurement of NT-proBNP may be valuable for the evaluation of treatment with
      DTCCB and vasodilators in patients with PAH.

PMID- 14674002
TI  - Prognostic factors for radiographic progression, radiographic damage, and
      disability in juvenile idiopathic arthritis.
AB  - OBJECTIVE: To investigate the rate of radiographic progression and identify
      prognostic factors of radiographic progression, radiographic damage, and physical
      disability in juvenile idiopathic arthritis (JIA). METHODS: Ninety-four JIA
      patients with a median disease duration of 1.1 years were followed up
      prospectively for a median of 4.5 years. Bilateral wrist radiographs were
      obtained at baseline, at 1 year, and at the last followup visit. Radiographic
      damage was assessed by the carpal length (Poznanski score), and physical
      disability by the Childhood Health Assessment Questionnaire (C-HAQ). Yearly
      radiographic progression, the Poznanski score at the final visit, and the C-HAQ
      score at the final visit were used as outcome measures. Baseline parameters
      included demographic, clinical, laboratory, and radiographic data. RESULTS: The
      mean +/- SD Poznanski score was -1.2 +/- 1.3 at baseline, -1.7 +/- 1.8 at the 1
      year visit, and -1.9 +/- 2.2 at the final visit (P < 0.0001). Radiographic
      progression was greater during the first year (mean +/- SD -0.5 +/- 1.1) than
      between the 1-year visit and the final visit (-0.2 +/- 1.3). The mean yearly
      radiographic progression during the entire study period was -0.1 +/- 0.4.
      Logistic regression analysis revealed that radiographic progression during the
      first year was the only baseline parameter that was predictive of all 3 study
      outcomes. The final Poznanski score was also predicted by the baseline Poznanski
      score, whereas female sex was protective against radiographic progression.
      CONCLUSION: We identified the prognostic factors for poorer outcome in
      polyarticular-course JIA. The changes in the early Poznanski score can be used to
      predict long-term joint damage and physical disability.

PMID- 14674003
TI  - Occurrence of Raynaud's phenomenon in children ages 12-15 years: prevalence and
      association with other common symptoms.
AB  - OBJECTIVE: Although Raynaud's phenomenon (RP) in adults is frequently reported as
      having been present since childhood, there have been no studies on the prevalence
      of RP in children. This study was undertaken to ascertain the prevalence of RP in
      children ages 12-15 years and to determine whether, as with other commonly
      reported symptoms, there were any associations with adverse psychosocial factors.
      METHODS: A previously validated self-administered RP questionnaire was
      distributed to 903 children ages 12-15 years, from 28 schools. The questionnaire
      also included questions on other common childhood symptoms and on adverse
      psychosocial factors. RESULTS: Seven hundred twenty children responded (80%), in
      whom the prevalence of RP was 15%. This was higher in girls (18% versus 12%) and
      increased with age. After adjustment for age and sex, there was an association
      with reporting of current pain, both in the arm/shoulder region and elsewhere in
      the body. There were no associations with psychosocial variables. CONCLUSION: RP
      is frequent in children ages 12-15 years. Unlike other common childhood symptoms,
      RP showed no association with psychosocial factors in this study.

PMID- 14674004
TI  - Incidence and predictors of large-artery complication (aortic aneurysm, aortic
      dissection, and/or large-artery stenosis) in patients with giant cell arteritis:
      a population-based study over 50 years.
AB  - OBJECTIVE: To determine the incidence and predictors of large-artery complication
      (aortic aneurysm, aortic dissection, and/or large-artery stenosis) in patients
      with giant cell arteritis (GCA). METHODS: The cohort of all residents of Olmsted
      County, Minnesota, in whom GCA was diagnosed between January 1, 1950, and
      December 31, 1999, was followed up. The incidence of aortic aneurysm, aortic
      dissection, and large-artery stenosis was determined. Possible predictors and
      correlates of large-artery complication were assessed. RESULTS: Forty-six
      incident cases of large-artery complication (representing 27% of the 168 patients
      in the cohort) were identified. These included 30 incident cases (18%) of aortic
      aneurysm and/or aortic dissection. Of these cases, 18 (11%) involved the thoracic
      aorta, with aortic dissection developing in 9 (5%). There were 21 incident cases
      (13%) of large-artery stenosis. Fifteen patients (9%) had incident cervical
      artery stenosis, and 6 (4%) had incident subclavian/axillary/brachial artery
      stenosis. One patient (0.6%) had incident iliac/femoral artery stenosis
      attributable to GCA. Hyperlipidemia and coronary artery disease were associated
      with aortic aneurysm and/or dissection (P < 0.05 for both). Cranial symptoms
      (headache, scalp tenderness, abnormal temporal arteries) were negatively
      associated with large-artery stenosis (hazard ratio [HR] 0.10 [95% confidence
      interval (95% CI) 0.03-0.35, P < 0.0005]), as was a higher erythrocyte
      sedimentation rate (HR 0.80 [95% CI 0.67-0.95, P < 0.05] per 10 mm/hour).
      CONCLUSION: Large-artery complication is common in GCA. Increased awareness of
      large-artery complication in GCA, particularly early-occurring aortic dissection,
      may decrease associated mortality.

PMID- 14674005
TI  - Mortality of large-artery complication (aortic aneurysm, aortic dissection,
      and/or large-artery stenosis) in patients with giant cell arteritis: a population
      based study over 50 years.
AB  - OBJECTIVE: To determine the mortality of giant cell arteritis (GCA) with large
      artery complication compared with that of GCA without large-artery complication.
      METHODS: An inception cohort of 168 residents of Olmsted County, Minnesota, in
      whom GCA was diagnosed between January 1, 1950, and December 31, 1999, was
      followed up. Mortality in patients with incident large-artery complication
      (aortic aneurysm, aortic dissection, and large-artery stenosis) was determined
      and compared with that in patients in whom large-artery complication did not
      develop. RESULTS: No difference in survival was observed between the total group
      of patients with any type of large-artery complication and patients without large
      artery complication or the general population. However, mortality was markedly
      increased in the 9 patients in whom thoracic aortic dissection developed (median
      survival 1.1 years [interquartile range 0.2-7.8 years]) compared with that in all
      other patients with GCA (P < 0.001). No difference in survival was observed
      between the group of patients with either aortic aneurysm and/or dissection
      (thoracic and/or abdominal aorta) and the group with GCA without large-artery
      complication. Survival of patients with GCA and large-artery stenosis was not
      different from that of patients with GCA without large-artery complication.
      CONCLUSION: Thoracic aortic dissection in GCA is associated with markedly
      increased mortality. Overall, mortality in the whole group of patients with GCA
      with large-artery complication was similar to that in patients with GCA without
      large-artery complication.

PMID- 14674006
TI  - Successful treatment of multicentric reticulohistiocytosis with alendronate:
      evidence for a direct effect of bisphosphonate on histiocytes.
AB  - We describe the case of a 44-year-old Japanese woman with severe nodular
      erythematous skin lesions and arthritis mutilans who was admitted for further
      treatment of multicentric reticulohistiocytosis. Skin and synovial biopsies
      showed heavy infiltration with tartrate-resistant acid phosphatase-positive
      histiocytes and multinucleated giant cells. Immunohistochemical analysis showed
      that some of the mononuclear cells in the skin were positive for RANKL. After 1
      month of Alendronate, an aminobisphosphonate, given at a dosage of 10 mg once a
      week intravenously for the first 6 weeks and then once a month thereafter, the
      arthritis and skin nodules improved, and the remission has continued for more
      than 2 years. The findings in this patient suggest that osteoclast-like
      multinucleated giant cells differentiate locally in the skin from infiltrating
      histiocytes with the help of RANKL-positive stromal cells and that alendronate
      acts directly on cells of monocyte/macrophage lineage in humans. Thus,
      alendronate should be added to the list of drugs for the treatment of
      multicentric reticulohistiocytosis.

PMID- 14674007
TI  - Successful tumor necrosis factor alpha blockade treatment in therapy-resistant
      sarcoidosis.
AB  - Sarcoidosis is a multisystemic disorder histologically characterized by a
      noncaseating granulomatous inflammatory process. The etiology remains unclear,
      but tumor necrosis factor alpha seems to play a crucial role. Herein we describe
      a patient with severe sarcoidosis involving the lung and liver. Various treatment
      regimens with azathioprine, methotrexate, cyclophosphamide, and pentoxifylline
      failed to control the disease. Therefore, salvage therapy with infliximab was
      commenced. Arthritis and pulmonary and liver involvement improved. We were then
      able to taper the corticosteroid treatment to a lower-dose regimen with no need
      for additional immunosuppressive treatment. To our knowledge, this is the first
      reported case of successful treatment of multiorgan sarcoidosis that was
      previously resistant to conventional therapy.

PMID- 14674008
TI  - Reduction in the evolution of murine type II collagen-induced arthritis by
      treatment with rosiglitazone, a ligand of the peroxisome proliferator-activated
      receptor gamma.
AB  - OBJECTIVE: The peroxisome proliferator-activated receptor gamma (PPARgamma) is a
      member of the nuclear receptor superfamily of ligand-dependent transcription
      factors related to retinoid, steroid, and thyroid hormone receptors. The
      thiazolidinedione rosiglitazone is a PPARgamma ligand that modulates the
      transcription of target genes. The aim of this study was to investigate the
      effects of rosiglitazone on the inflammatory response in mice with collagen
      induced arthritis (CIA). METHODS: CIA was induced in DBA/1J mice by an
      intradermal injection of 100 microl of an emulsion of bovine type II collagen
      (CII; 100 microg) in Freund's complete adjuvant (CFA) at the base of the tail. On
      day 21, a second injection of CII in CFA was administered. Rosiglitazone (10
      mg/kg/day) or vehicle (10% DMSO) was administered beginning on day 25 (arthritis
      onset) until day 35. Clinical, radiographic, histopathologic, and laboratory
      assessments were performed. RESULTS: Mice immunized with CII in CFA developed
      erosive arthritis of the hind paws. Macroscopic evidence of CIA first appeared as
      periarticular erythema and edema of the hind paws. The incidence of CIA was 100%
      by day 27 in the CII-challenged mice, and the severity progressed over the 35-day
      study period. Radiographic evaluation revealed focal resorption of bone.
      Histopathologic features of CIA included erosion of cartilage at the joint
      margins. Rosiglitazone treatment ameliorated the clinical signs on days 26-35 and
      improved the histologic findings in the joint and paw. The degree of oxidative
      and nitrosative damage was significantly reduced in rosiglitazone-treated mice,
      as indicated by elevation of malondialdehyde levels, formation of nitrotyrosine,
      and activation of poly(ADP-ribose) polymerase. Plasma levels of the
      proinflammatory cytokines tumor necrosis factor, interleukin-1beta, and
      interleukin-6 were also significantly reduced by rosiglitazone treatment.
      CONCLUSION: These data demonstrate that rosiglitazone exerts an antiinflammatory
      effect on chronic inflammation and is able to ameliorate the tissue damage
      associated with CIA.

PMID- 14674009
TI  - Splenectomy attenuates streptococcal cell wall-induced arthritis and alters
      leukocyte activation.
AB  - OBJECTIVE: To investigate the role of the spleen in the pathogenesis of
      streptococcal cell wall (SCW)-induced arthritis and determine the impact of
      splenectomy on monocytes and T cells involved in the arthritis. METHODS: Female
      Lewis rats were separated into 4 groups: 1) saline-injected, sham-operated; 2)
      saline-injected, splenectomized; 3) peptidoglycan-polysaccharide (PG-PS)
      injected, sham-operated; and 4) PG-PS-injected, splenectomized. After a 10-day
      recovery period, rats received a single intraperitoneal injection of saline or PG
      PS (25 microg rhamnose/gm body weight). We evaluated the effect of splenectomy on
      joint inflammation, histopathology, leukocyte subtypes in blood and lymph nodes,
      cytokines, and cell surface expression of CD44 and CD45RC in the chronic phase of
      the disease (day 28). RESULTS: Splenectomy dramatically decreased chronic joint
      inflammation and histopathologic damage as well as altered cell types in lymph
      nodes and peripheral blood, as analyzed by flow cytometry. Nitric oxide (NO)
      production, levels of interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor
      alpha, and a biomarker of Th1 cell predominance correlated with the level of
      joint inflammation. Surprisingly, in splenectomized animals, increased expression
      of adhesion molecules thought to track T cells to inflamed tissue were observed
      in lymph nodes. CONCLUSION: The result of splenectomy was attenuation of SCW
      induced arthritis and changes in mediators of inflammation, including T cell
      subsets, proinflammatory cytokines, and NO production. Splenectomy may remove an
      important antigen reservoir and alter immune cell activation in the SCW-induced
      arthritis model.

PMID- 14674010
TI  - Chemokine receptor expression and in vivo signaling pathways in the joints of
      rats with adjuvant-induced arthritis.
AB  - OBJECTIVE: This study was undertaken to characterize the role of CC chemokines
      and their receptors in rat adjuvant-induced arthritis (AIA), a model for
      rheumatoid arthritis (RA). Furthermore, we investigated the signaling pathways
      associated with CC receptors as well as the cell type distribution of the
      receptors. METHODS: Using TaqMan real-time reverse transcription-polymerase chain
      reaction, Western blot analysis, and immunohistochemistry, we defined chemokine
      and chemokine receptor messenger RNA (mRNA) expression, CC chemokine receptor
      (CCR) protein activation during the disease course, CCR-associated signaling
      pathways, and immunopositive CCR5, phosphorylated signal transducer and activator
      of transcription 1 (p-STAT-1), and p-STAT-3 cells in rat AIA versus control
      joints. RESULTS: We showed significant up-regulation of CCR1, CCR2, CCR5, and
      macrophage inflammatory protein 1beta/CCL4 mRNA in AIA on post-adjuvant injection
      day 18, coincident with peak inflammation. Additionally, increases in tyrosine
      phosphorylation of CCR1 (days 14, 18, 21, and 24), CCR2 (days 14 and 18), and
      CCR5 (days 14, 18, and 21) were detected in AIA rats compared with control
      (nonarthritic) rats. JAK-1, STAT-1, and STAT-3 were associated with CCR1 and were
      highly tyrosine phosphorylated on days 14 and 18. Moreover, CCR2 was associated
      with JAK-2, STAT-1, and STAT-3 on day 18. The association of STAT-1 and STAT-3
      with CCR5 on days 18 and 21 correlated with JAK-1 phosphorylation and binding on
      day 18. However, the activation of JNK was not associated with CCR5 activation in
      rat AIA. Immunohistochemical analysis demonstrated that the expression of CCR5, p
      STAT-1, and p-STAT-3 was detected on synovial lining cells, macrophages, and
      endothelial cells in arthritic rat ankles on post-adjuvant injection day 18.
      While the majority of the CCR5 and p-STAT-1 immunostaining was on synovial lining
      cells and macrophages, p-STAT-3 was predominantly expressed on endothelial cells.
      CONCLUSION: CCR1, CCR2, and CCR5 mRNA expression and tyrosine phosphorylation
      increased with peak inflammation in the AIA model. CCR1, CCR2, and CCR5 tyrosine
      phosphorylation are associated with the JAK/STAT-1/STAT-3 pathway at different
      stages of rat AIA, as well as with macrophage and endothelial cell infiltration.
      However, their signaling activation overlaps with peak inflammation. Up
      regulation and activation of CCRs may play a role in macrophage and endothelial
      cell infiltration in rat AIA joints in addition to activating the associated
      signaling pathways. The downstream intermediate signaling proteins associated
      with CC receptors may be used as potential tools to control inflammation in RA.

PMID- 14674011
TI  - The genetic control of rheumatoid factor production in a rat model of rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate the genetic regulation of rheumatoid factor (RF) in a
      rat model of rheumatoid arthritis, in order to gain understanding of the
      enigmatic role of RF in the disease. METHODS: IgM-RF and IgG-RF, as well as total
      levels of immunoglobulins of different subclasses, were measured in sera from
      rats with pristane-induced arthritis (PIA). The major gene regions were
      identified by linkage analysis of genetically segregating crosses. RESULTS: The
      production of RF was found to correlate with development of arthritis and to be
      higher in females than in males. Surprisingly, the relatively arthritis-resistant
      E3 strain had higher levels of RF than the arthritis-susceptible DA strain. In an
      (E3 x DA)F(2) cohort a major locus controlling the levels of IgM-RF in serum was
      identified on chromosome 11 (Rf1) and another on chromosome 16 (Rf3), and these
      were not related to arthritis susceptibility. However, the Rf2 locus on
      chromosome 4 controlled IgG-RF levels, IgG2a levels, and chronic arthritis in
      males (Pia5). Some previously defined arthritis loci (Pia4, Pia6, Pia7, and Pia8)
      were found to also control immunoglobulin levels in serum. CONCLUSION: RFs are
      produced in the rat PIA model and correlate with development of arthritis. Gene
      regions controlling RF and serum immunoglobulin levels were identified, of which
      some cosegregated with arthritis. This suggests a new focus of study to elucidate
      the role of RF in the pathogenesis of arthritis.

PMID- 14674012
TI  - Antiidiotypic antibodies neutralize autoantibodies that inhibit cholinergic
      neurotransmission.
AB  - OBJECTIVE: Functional autoantibodies that inhibit M(3) muscarinic receptor (M3R)
      mediated neurotransmission have been reported in patients with Sjogren's syndrome
      (SS) and in patients with scleroderma. Because of limited reports that
      intravenous immunoglobulin (IVIG) improves dysautonomia in primary SS, we
      investigated whether IVIG neutralizes the effect of anti-M3R antibodies on colon
      smooth muscle contractions, in an in vitro functional assay. METHODS: IgG
      obtained from patients with primary SS, patients with rheumatoid arthritis and
      secondary SS, and patients with scleroderma was tested, before and after
      coincubation with equimolar amounts of IVIG or its F(ab')(2) and Fc fractions,
      for the ability to inhibit carbachol-evoked colon smooth muscle contractions. In
      addition, patient IgG was passed through an IVIG F(ab')(2) column, and unretained
      IgG was tested for functional activity on colon smooth muscle strips. Purified
      IgG obtained from healthy adults was also examined for a neutralizing effect on
      anti-M3R antibody activity. RESULTS: Inhibition of colon contractions was
      mediated by the Fab fraction of patient IgG. Coincubation of IgG from the 3
      patient groups with IVIG or its F(ab')(2) fragment neutralized anti-M3R antibody
      mediated inhibition of cholinergic smooth muscle contractions. Preabsorption of
      patient IgG with Sepharose-bound IVIG F(ab')(2) removed the anti-M3R inhibitory
      activity. In addition, purified IgG from each of 4 healthy adults neutralized the
      functional autoantibodies. CONCLUSION: Anti-M3R antibody activity does not
      require receptor crosslinking. Antiidiotypic antibodies present in pooled IgG
      neutralize patient IgG-mediated inhibition of M3R cholinergic neurotransmission,
      providing a rationale for IVIG as a treatment of autonomic dysfunction in
      patients with SS and patients with scleroderma. Furthermore, antiidiotypic
      antibodies in healthy individuals may prevent the emergence of pathogenic anti
      M3R autoantibodies.

PMID- 14674013
TI  - Development of autoimmune exocrinopathy resembling Sjogren's syndrome in
      adoptively transferred mice with autoreactive CD4+ T cells.
AB  - OBJECTIVE: The pathologic mechanisms responsible for organ-specific tissue damage
      in primary Sjogren's syndrome (SS) remain unclear, but it has been suggested that
      the pathology is mediated by autoreactive CD4+ T cells infiltrating the salivary
      and lacrimal glands. This study was undertaken to investigate whether alpha
      fodrin autoantigen-specific autoreactive CD4+ T cells are capable of inducing
      autoimmune lesions. METHODS: A total of 45 synthetic alpha-fodrin peptides
      designed to be 20 amino acid residues in length were generated. To establish an
      autoreactive T cell line, limiting dilution analysis (LDA) was performed on lymph
      node cells (LNCs) in the presence of alpha-fodrin peptides. The effects of
      adoptive transfer of autoreactive CD4+ T cells into normal syngeneic recipients
      were investigated. RESULTS: Autoreactive CD4+ T cell lines that recognize
      synthetic alpha-fodrin peptide, which produced Th1 cytokines and showed cytotoxic
      activities, were established in a murine model for SS. T cell receptor V(beta)
      usage and third complementarity-determining region (CDR3) sequences indicated
      that in some cases V(beta)6-CDR3 genes matched between the tissue-infiltrating T
      cells and the autoreactive T cell lines. Adoptive transfer of the autoreactive
      CD4+ T cells into normal syngeneic recipients induced autoimmune lesions quite
      similar to those of SS. CONCLUSION: Our data help to elucidate the pathogenic
      mechanisms responsible for tissue destruction in autoimmune exocrinopathy and
      indicate that autoreactive CD4+ T cells play a pivotal role in the development of
      murine SS.

PMID- 14674015
TI  - Fibrillin 1 as an autoantigen in the spondylarthropathies? Comment on the
      conference summary by McGonagle et al.

PMID- 14674016
TI  - Swollen joint count as a predictor of response to anti-tumor necrosis factor
      alpha therapy in rheumatoid arthritis: comment on the article by Sokka and
      Pincus.

PMID- 14674017
TI  - Eligibility of rheumatoid arthritis patients seen in clinical practice for
      rheumatoid arthritis clinical trials: comment on the article by Sokka and Pincus.

PMID- 14674019
TI  - Genetic variation in CCR5 does not predict clinical outcome in inflammatory
      arthritis.

PMID- 14674021
TI  - The plant response: stress in the daily environment.

PMID- 14674022
TI  - Enhancing rice resistance to fungal pathogens by transformation with cell wall
      degrading enzyme genes from Trichoderma atroviride.
AB  - Three genes encoding for fungal cell wall degrading enzymes (CWDEs), ech42, nag70
      and gluc78 from the biocontrol fungus Trichoderma atroviride were inserted into
      the binary vector pCAMBIA1305.2 singly and in all possible combinations and
      transformed to rice plants. More than 1800 independently regenerated plantlets in
      seven different populations (for each of the three genes and each of the four
      gene combinations) were obtained. The ech42 gene encoding for an endochitinase
      increased resistance to sheath blight caused by Rhizoctonia solani, while the
      exochitinase-encoding gene, nag70, had lesser effect. The expression level of
      endochitinase but exochitinase was correlated with disease resistance.
      Nevertheless, exochitinase enhanced the effect of endochitinase on disease
      resistance when the two genes co-expressed in transgenics. Resistance to
      Magnaporthe grisea was found in all kinds of regenerated plants including that
      with single gluc78. A few lines expressing either ech42 or nag70 gene were immune
      to the disease. Transgenic plants are being tested to further evaluate disease
      resistance at field level. This is the first report of multiple of expression of
      genes encoding CWDEs from Trichoderma atroviride that result in resistance to
      blast and sheath blight in rice.

PMID- 14674023
TI  - Programmed cell death features in apple suspension cells under low oxygen
      culture.
AB  - Suspension-cultured apple fruit cells (Malus pumila Mill. cv. Braeburn) were
      exposed to a low oxygen atmosphere to test whether programmed cell death (PCD)
      has a role in cell dysfunction and death under hypoxic conditions. Protoplasts
      were prepared at various times after low oxygen conditions were established, and
      viability tested by triple staining with fluorescein diacetate (FDA), propidium
      iodide (PI) and Hoechst33342 (HO342). DNA breakdown and phosphatidylserine
      exposure on the plasma membrane were observed using terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL), and annexin V binding. About
      30% of protoplasts from cells after 48 h under low oxygen showed an increased
      accumulation of HO342, indicating increased membrane permeability. Positive TUNEL
      and annexin V results were also only obtained with protoplasts from cells under
      low oxygen. The results suggest that apple cell death under low oxygen is at
      least partially PCD mediated, and may explain tissue breakdown under controlled
      atmosphere (low oxygen) conditions in apple fruit.

PMID- 14674024
TI  - Preliminary study on a gravity-insensitive rice mutant.
AB  - A gravity-insensitive mutant was isolated from rice (Oryza sativa L. cv. Zhonghua
      11) transformed by Agrobacterium tumefaciens. The mutant's shoot growth
      (prostrate growth) was insensitive to gravity; whereas root growth displayed a
      normal positive gravitropism. Histological observation of root caps and leaf
      sheaths indicated that there was no significant difference in the number and size
      of amyloplasts in cells of the mutant and cells of the wild type.

PMID- 14674025
TI  - Improved elastase production by Bacillus sp. EL31410--further optimization and
      kinetics studies of culture medium for batch fermentation.
AB  - An efficient culture medium producing a bacterial elastase with high yields was
      developed further following preliminary studies by means of response surface
      method. Central composite design (CCD) and response surface methodology were
      applied to optimize the medium constituents. A central composite design was used
      to explain the combined effect of three medium constituents, viz, glucose,
      K(2)HPO(4), MgSO(4).7H(2)O. The strain produced more elastase in the completely
      optimized medium, as compared with the partially optimized medium. The fitted
      model of the second model, as per RSM, showed that glucose was 7.4 g/100 ml,
      casein 1.13 g/100 ml, corn steep flour 0.616 g/100 ml, K(2)HPO(4) 0.206 g/100 ml
      and MgSO(4).7H(2)O 0.034 g/100 ml. The fermentation kinetics of these two culture
      media in the flask experiments were analyzed. It was found that the highest
      elastase productivity occurred at 54 hours. Higher glucose concentration had
      inhibitory effect on elastase production. At the same time, we observed that the
      glucose consumption rate was slow in the completely optimized medium, which can
      explain the lag period of the highest elastase production. Some metal ions and
      surfactant additives also affected elastase production and cell growth.

PMID- 14674026
TI  - Ex vivo expansions and transplantations of mouse bone marrow-derived
      hematopoietic stem/progenitor cells.
AB  - To examine the effects of co-culture with bone marrow mesenchymal stem cells on
      expansion of hematopoietic stem/progenitor cells and the capacities of rapid
      neutrophil engraftment and hematopoietic reconstitution of the expanded cells, we
      expanded mononuclear cells (MNCs) and CD34+/c-kit+ cells from mouse bone marrow
      and transplanted the expanded cells into the irradiated mice. MNCs were isolated
      from mouse bone marrow and CD34+/c-kit+ cells were selected from MNCs by using
      MoFlo Cell Sorter. MNCs and CD34+/c-kit+ cells were co-cultured with mouse bone
      marrow-derived mesenchymal stem cells (MSCs) under a two-step expansion. The
      expanded cells were then transplanted into sublethally irradiated BDF1 mice.
      Results showed that the co-culture with MSCs resulted in expansions of median
      total nucleated cells, CD34+ cells, GM-CFC and HPP-CFC respectively by 10.8-, 4.8
      , 65.9- and 38.8-fold for the mononuclear cell culture, and respectively by 76.1
      , 2.9-, 71.7- and 51.8-fold for the CD34+/c-kit+ cell culture. The expanded cells
      could rapidly engraft in the sublethally irradiated mice and reconstitute their
      hematopoiesis. Co-cultures with MSCs in conjunction with two-step expansion
      increased expansions of total nucleated cells, GM-CFC and HPP-CFC, which led us
      to conclude MSCs may create favorable environment for expansions of hematopoietic
      stem/progenitor cells. The availability of increased numbers of expanded cells by
      the co-culture with MSCs may result in more rapid engraftment of neutrophils
      following infusion to transplant recipients.

PMID- 14674027
TI  - Cloning and GST-fused expression in E. coli of mouse beta-1,4
      galactosyltransferase.
AB  - Beta-1,4-galactosyltransferase (beta4Gal-T) (EC 2.4.1.38) plays a multifunctional
      role in many aspects of normal cell physiology. By now, several dozens of
      beta4Gal-T genes have been cloned, separated from mouse, chick, bovine, human,
      etc. This paper presents the cloning and GST-fused expression of mouse beta4Gal-T
      gene in Escherichia coli (E. coli). The target gene was cloned by PCR, followed
      by identification by DNA sequencing and expression in E.coli with isopropyl-beta
      D-thiogalactoside (IPTG) gradient concentrations, products of which were
      separated on SDS-PAGE showing that the target protein had the same molecular
      weight as that of mouse beta4Gal-T. The transcriptional product of beta4Gal-T
      gene was proved by Western hybridization analysis to be due to GST-fusion.

PMID- 14674028
TI  - A pair of two-component regulatory genes ecrA1/A2 in S. coelicolor.
AB  - Two-component genes are kinds of genetic elements involved in regulation of
      antibiotic production in Streptomyces coelicolor. DNA microarray analysis
      revealed that ecrA1/A2, which mapped at distant sites from red locus and encode
      respectively the kinase and regulator, expressed coordinately with genes of Red
      specific biosynthetic pathway. ecrA1 and ecrA2 gene-disruptive mutants were
      constructed using homogenotisation by reciprocal double crossover. Fermentation
      data showed that the undecylprodigiosin (Red) level of production was lower than
      that of wild-type strain. However, the change of the actinorhodin (Act)
      production level was not significant compared with wild type. Thus, these
      experiment results confirmed that the two-component system ecrA1/A2 was positive
      regulatory element for red gene cluster.

PMID- 14674029
TI  - Degradation of chlorophenol by in-situ electrochemically generated oxidant.
AB  - A novel in-situ electrochemical oxidation method was applied to the degradation
      of wastewater containing chlorophenol. Under oxygen sparging, the strong oxidant,
      hydrogen dioxide, could be in-situ generated through the reduction of oxygen on
      the surface of the cathode. The removal rate of chlorophenol could be increased
      149% when oxygen was induced in the electrochemical cell. The promotion factor
      was estimated to be about 82.63% according to the pseudo-first-order reaction
      rate constant (min(-1)). Important operating parameters such as current density,
      sparged oxygen rate investigated. Higher sparged oxygen rate could improve the
      degradation of chlorophenol. To make full use of oxygen, however, sparged oxygen
      rate of 0.05 m(3)/h was adopted in this work. Oxidation-reduction potential could
      remarkably affect the generation of hydrogen peroxide. It was found that the
      removal rate of chlorophenol was not in direct proportion to the applied current
      density. The optimum current density was 3.5 mA/cm(2) when initial chlorophenol
      concentration was 100 mg/L and sparged oxygen rate was 0.05 m(3)/h.

PMID- 14674030
TI  - A large scale screen for genes (3rd chromosome) related to Wingless signaling
      pathway.
AB  - A wing specific F1 genetic screen was carried out using the powerful Drosophila
      genetic system, combined with yeast FRT/FLP and GAL4/UAS system. Form the wing
      phenotypes and germline clone embryonic cuticle phenotypes observed in these
      mutant alleles, a number of mutant alleles of known or unknown genes were
      isolated. Among them, fifteen mutant alleles related to Wingless signal
      transduction were further isolated; the arm of these mutations located were
      determined, and their location in the chromosome were roughly mapped.

PMID- 14674031
TI  - Effect of polychlorinated biphenyls on spermatogenesis and testosterone secretion
      in adult cocks.
AB  - The effects of polychlorinated biphenyls (PCBs) on reproduction of adult cocks
      were studied by gavaging peanut oil or PCBs (Aroclor 1254, 50 mg/kg) once a week
      for six consecutive weeks. Physiological parameters were recorded and gonads were
      removed at the end of experiment for histological examination. The results showed
      that there was no significant difference between the control and treatment group
      in body weight, respiration rate, heart rate, body temperature, and the numbers
      of red and white blood cells. However, there was a marked decrease in the
      testicular weight and serum testosterone level after PCB treatment. Morphological
      studies manifested severe damage of the seminiferous tubules by PCB. The number
      of the germ cells at the different developmental stages was decreased and
      condensed nuclei were observed in most of these cells. This study revealed that
      the reproductive function of the adult cocks is sensitive to PCBs, which
      inhibited mainly spermatogenesis and testosterone secretion.

PMID- 14674032
TI  - Degradation kinetics and mechanisms of phenol in photo-Fenton process.
AB  - Phenol degradation in photochemically enhanced Fenton process was investigated in
      this work. UV-VIS spectra of phenol degradation showed the difference between
      photo-Fenton process and UV/H(2)O(2), which is a typical hydroxyl radical
      process. A possible pathway diagram for phenol degradation in photo-Fenton
      process was proposed, and a mathematical model for chemical oxygen demand (COD)
      removal was developed. Operating parameters such as dosage of H(2)O(2) and
      ferrous ions, pH, suitable carrier gas were found to impact the removal of COD
      significantly. The results and analysis of kinetic parameters calculated from the
      kinetic model showed that complex degradation of phenol was the main pathway for
      removal of COD; while hydroxyl radicals acted weakly in the photo-Fenton
      degradation of phenol.

PMID- 14674033
TI  - Heterogeneous UV/Fenton catalytic degradation of wastewater containing phenol
      with Fe-Cu-Mn-Y catalyst.
AB  - The heterogeneous UV/Fenton process with the appropriate amount of Fe-Mn-Cu-Y as
      catalyst was developed and various operation conditions for the degradation of
      phenol were evaluated. The results indicated that by using the heterogeneous
      UV/Fenton process, the COD(cr) removal rate reached almost 100% for wastewater
      containing phenol. Compared with the homogeneous process, the developed catalyst
      could be used at wider pH range in the UV/Fenton process. Comparison of various
      heterogeneous process showed that heterogeneous UV/Fenton process was best. The
      heterogeneous UV/Fenton process with Fe-Mn-Cu-Y catalyst is highly efficient in
      degrading various organic pollutants.

PMID- 14674034
TI  - ZnS0.8Se0.2 film for high resolution liquid crystal light valve.
AB  - The structural characteristics and optical and electrical properties of molecular
      beam-epitaxy (MBE) grown ZnS(0.8)Se(0.2) thin films on indium-tin-oxide (ITO)
      glass substrates were investigated in this work. The X-ray diffraction (XRD)
      results indicated that high quality polycrystalline ZnS(0.8)Se(0.2) thin film
      grown at the optimized temperature had a preferred orientation along the (111)
      planes. The transmission electron microscopy (TEM) cross-sectional micrograph of
      the sample showed a well defined columnar structure with lateral crystal
      dimension in the order of a few hundred angstroms. Ultraviolet (UV)
      photoresponsivity as high as 0.01 A/W had been demonstrated and for wavelengths
      longer than 450 nm, the response was down from the peak response by more than 3
      orders of magnitude. The thin ZnS(0.8)Se(0.2) photosensor layer, with a wide
      energy gap and anisotropic electrical property, makes a transmission UV liquid
      crystal light valve (LCLV) with high resolution feasible.

PMID- 14674035
TI  - Reductive cyclodimerization of arylmethylidenemalononitriles promoted by samarium
      and catalytic amount of iodine: facile synthesis of cyclopentene derivatives.
AB  - Samarium and a catalytic amount of iodine were used to obtain functionalized
      cyclopentenes by reductive dimerization followed by intramolecular cyclization of
      1,1-dicyanoalkenes under mild conditions.

PMID- 14674036
TI  - Identification of genes differentially expressed in monocyte-derived dendritic
      cells with 1alpha,25-dihydroxyvitamin D3 using cDNA arrays.
AB  - In order to study the molecular mechanism of the inhibitory effect of 1,25
      dihydroxyvitamin D(3) on dendritic cells, experiments were performed using Atlas
      cDNA expression arrays from Clonetech to identify the differentially expressed
      genes of dendritic cells by 1,25-dihydroxyvitamin D(3). Analysis of cDNA arrays
      revealed changes in the expression of 9 genes, including those involved in DNA
      binding and transcription, extracellular cell signaling and communication,
      intracellular transducers, as well as cell adhesions. The results indicated that
      a multiple molecular network is involved in the inhibitory role of 1,25
      dihydroxyvitamin D(3) on dendritic cells. The Atlas Array technology may
      facilitate the elucidation of complex pharmacological process of 1,25
      dihydroxyvitamin D(3) on dendritic cells.

PMID- 14674037
TI  - Enantioselective assay of S+ - and R- -propafenone in human urine by using RP
      HPLC with pre-column chiral derivatization.
AB  - The enantioselective assay for S(+)- and R(-)-propafenone (PPF) in human urine
      that developed in this work involves extraction of propafenone from human urine
      and using S(+)-propafenone as internal standard, chiral derivatization with
      2,3,4,6-tetra-O-beta-D-glucopranosyl isothiocyanate, and quantitation by an RP
      HPLC system with UV detection (lambda=220 nm). A baseline separation of
      propafenone enantiomers was achieved on a 5-microm reverse phase ODS column, with
      a mixture of acetic acid (25:12:0.02,v/v) as mobile phase. There was good linear
      relationship from 24.9 ng/ml to 1875.0 ng/ml for both of enantiomers. The
      regression equations of the standard curves based on C(S-PPF) (or C(R-PPF))
      versus ratio of A(S-PPF)/A(S) (or A(R-PPF)/A(S)) were y=0.0032x-0.081, (r=0.999)
      for S-PPF and y=0.0033x+0.0039, (r=0.998) for R-PPF, respectively. The method's
      limit of detection was 12.5 ng/ml for both enantiomers, and the method's limit of
      quantitation was 28.2+/-0.52 ng/ml for S-PPF, 30.4+/-methanol:water:glacial 0.53
      ng/ml for R-PPF (RSD<8%, n=5). The analytical method yielded average recovery of
      98.9% and 100.4% for S-PPF and R-PPF, respectively. The relative standard
      deviation was no more than 6.11% and 6.22% for S-PPF and R-PPF, respectively. The
      method enabled study of metabolism of S(+)- and R(-)-propafenone in human urine.
      The results from 7 volunteers administered 150 mg racemic propafenone indicated
      that propafenone enantiomers undergo stereoselective metabolism and that in the
      human body, S(+)-propafenone is metabolized more extensively than R(-)
      propafenone.

PMID- 14674038
TI  - Homoharringtonine induces apoptosis of endothelium and down-regulates VEGF
      expression of K562 cells.
AB  - Homoharringtonine (HHT) has currently been used successfully in the treatment of
      acute and chronic myeloid leukemias and has been shown to induce apoptosis of
      different types of leukemic cells in vitro. Emerging evidence suggests that
      angiogenesis may play an important role in hematological malignancies, such as
      leukemia. However, whether HHT can relieve leukemia by anti-angiogenesis is still
      unknown. We investigated the anti-angiogenesis potential of HHT with the human
      umbilical vein endothelial cell line (ECV304) and leukemic cell line (K562) in
      vitro. Cellular proliferation was determined by MTT assay and apoptosis was
      analyzed by flow cytometry. The mRNA expression of vascular endothelial growth
      factor (VEGF) was assessed by RT-PCR and VEGF protein production was detected by
      Western blot. Inhibition of cell proliferation and induction of apoptosis by HHT
      were discovered in ECV304 cells, and appeared in a dose- and time-dependent
      manner. Also, treatment with HHT caused down-regulation of VEGF mRNA expression
      in K562 cells in similar dose- and time-dependent manner and inhibition of VEGF
      protein production in K562 cells in response to the enhancing concentration of
      HHT. The results demonstrated that HHT could also induce apoptosis in endothelium
      and down-regulate VEGF expression in K562 cells. In conclusion, we believe HHT
      has anti-angiogenesis potential and speculate that HHT might exert its anti
      leukemia effects via reduction of angiogenesis.

PMID- 14674039
TI  - Expression and significance of cyclin D1, p27kip1 protein in bronchioloalveolar
      carcinoma.
AB  - PURPOSE: To investigate the relationship between expression of cell cycle-related
      protein cyclin D1, p27kip1 and the pathogenesis of bronchioloalveolar carcinoma
      (BAC) and the value of prediction of prognosis. METHODS: Cyclin D1 and p27kip1
      protein were detected by immunohistochemical En Vision method in 43 BACs.
      RESULTS: The positivity of cyclin D1 in BAC was 65.1% (28/43), which was
      significantly higher than that in normal pulmonary tissue (0/13), P<0.01. No
      statistically significant association was found between cyclin D1 expression data
      and sex, age, tobacco-use history, histologic subtype (mucinous vs nonmucinous),
      stromal fibrosis, lymph node metastasis, clinical stage or postoperative survival
      period (P>0.05), while cyclin D1 expression was found to be negatively correlated
      with tumor size (P<0.05). The positivity of p27kip1 in BACs was 51.2% (22/43),
      significantly lower than that in normal pulmonary tissue (12/13), P<0.01. p27kip1
      expression level was not associated with sex, age, tobacco-use history, tumor
      size or histologic subtype (P>0.05), but was negatively correlated with stromal
      fibrosis, lymph node metastasis and clinical stage (P<0.05); and positively
      associated with postoperative survival period (P<0.01). The survival rate of
      p27kip1 positive group was significantly higher than that of p27kip1 negative
      group (P<0.01). No statistically significant correlation was found between cyclin
      D1 and p27kip1 expression. CONCLUSIONS: Increased cyclin D1 expression and
      decreased p27kip1 expression are related to the pathogenesis of BAC; decreased
      p27kip1 expression is associated with metastasis progression; immunodetection of
      p27kip1 is useful for assessment of prognosis.

PMID- 14674040
TI  - Distribution of H.pylori antigens in gastric mucosa and its significance.
AB  - OBJECTIVE: To investigate the distribution of H.pylori antigens in the gastric
      mucosa in patients with H.pylori infection, and the relationship between the
      distribution and gastric cancer. METHODS: Of 112 patients confirmed by
      pathological study to have chronic superficial gastritis, precancerous changes
      (chronic atrophic gastritis, intestinal metaplasia or atypical hyperplasia) and
      gastric cancer, 28 were H.pylori negative and 84 were H.pylori positive. H.pylori
      antigens in the gastric mucosa were detected by immunohistochemistry. RESULTS:
      The H.pylori positive group, comprised 12 of 22 (50.0%) in the chronic
      superficial gastritis group, 22 of 25 (88.0%) in the precancerous changes group
      and 13 of 35 (37.1%) in the gastric cancer group. The positive rates of H.pylori
      antigens in the cytoplasm progressively increased, respectively at 0.0% (0/12),
      63.6% (14/22) and 84.6% (11/13) for the same groups (chi(2)=19.76, P=0.000);
      H.pylori antigens were located in the mucus layer and above the neck of the
      mucosal gland in 9 of 12 (75.0%) cases with chronic superficial gastritis, at the
      neck of the mucosal gland and the isthmus in 12 of 22 (54.5%) cases with
      precancerous changes, below the isthmus in 9 of 13 (69.2%) cases with gastric
      cancer (chi(2)=25.30, P=0.000). In the H.pylori negative group, no H.pylori
      antigen was observed. CONCLUSION: With the progression of chronic superficial
      gastritis-->precancerous changes-->gastric cancer, H.pylori antigens
      progressively migrated from the outer part to the inner part of the cell, and
      from the superficial to the deep gastric mucosa.

PMID- 14674041
TI  - MRS study on lentiform nucleus in idiopathic Parkinson's disease with unilateral
      symptoms.
AB  - OBJECTIVE: To investigate changes in magnetic resonance spectroscopy (MRS) of
      lentiform nucleus during the early stage of Parkinson's disease. METHODS: Twenty
      five patients with idiopathic Parkinson disease with unilateral symptoms (IPDUS)
      and 25 healthy volunteers were enrolled in this study. MRS of the lentiform
      nucleus in each patient was taken and then concentrations of N-acetylaspartate
      (NAA), Creatine (Cr) and Choline (Cho) were calculated. RESULTS: Compared to that
      in the control, NAA/ (Cho+Cr) was significantly lower in the lentiform nucleus
      contralateral to symptoms and even that in the ipsilateral side in IPDUS patients
      (all P<0.05); while there was no difference between the two sides in the healthy
      volunteer (P>0.05). The ratio of NAA/(Cho+Cr) ipsilateral to the sympatomatic
      side of the patient was also lower than that of the control (P<0.05).
      CONCLUSIONS: There might be some changes with MRS on the lentiform nucleus during
      the early stage of idiopathic Parkinson's disease with unilateral symptom. MRS
      may be one of the reliable methods for early or even sub-clinical diagnosis.

PMID- 14674042
TI  - Oral anticoagulation and stroke in atrial fibrillation.

PMID- 14674043
TI  - Oral anticoagulation and stroke in atrial fibrillation.

PMID- 14674044
TI  - Molecular epidemiology of tuberculosis.

PMID- 14674045
TI  - Considerations on the stigma of mental illness.

PMID- 14674046
TI  - Stigma and the daily news: evaluation of a newspaper intervention.
AB  - OBJECTIVE: To evaluate a media intervention designed to improve one newspaper's
      portrayal of mental illnesses, specifically, schizophrenia. The project was part
      of an international antistigma program, Open the Doors, organized by the World
      Psychiatric Association. METHODS: The media intervention attempted to influence
      news content directly by providing reporters with more accurate background
      information and helping them develop more positive story lines. The evaluation
      compared story content and length over a 24-month period: 8 months prior to the
      antistigma intervention and 16 months postintervention. RESULTS: Positive stories
      outnumbered negative stories by a factor of 2 in both pre- and postperiods.
      Positive mental health stories increased by 33% in the postintervention period
      and their word count increased by an average of 25%. Stories about schizophrenia
      also increase by 33%, but their word count declined by 10%. At the same time,
      negative stories about mental illness increased by 25% and their word count by
      100%. The greatest increase was in negative news about schizophrenia.
      Stigmatizing stories about schizophrenia increased by 46%, and their length
      increased from 300 to 1000 words per story per month. CONCLUSION: The immediate
      effects of the media intervention were positive, resulting in more and longer
      positive news stories about mental illness and more positive news stories about
      schizophrenia. However, when considered from a broader perspective, locally
      focused efforts yielded meager results in light of the larger increases in
      negative news, particularly in negative news concerning people with schizophrenia
      -the target group for the program.

PMID- 14674047
TI  - Interventions to reduce the stigma associated with severe mental illness:
      experiences from the open the doors program in Germany.
AB  - Stigma associated with mental illness and psychiatric treatment and the
      discrimination toward people with mental illnesses that frequently results from
      this are main obstacles preventing early and successful treatment. To reduce such
      stigma and discrimination, especially toward people with schizophrenia, the World
      Psychiatric Association antistigma program Open the Doors is currently being
      implemented in 27 countries. Since August 1999, the campaign has been executed in
      7 project centres in Germany. Public information programs and educative measures
      aimed at selected target groups should improve the public's knowledge regarding
      symptomatology, causes, and treatment options for schizophrenia and
      schizophreniform disorders. Improved knowledge should in turn abolish prejudice
      and negative perceptions and facilitate the social reintegration of those
      suffering from mental illness.

PMID- 14674048
TI  - Determinants of the public's preference for social distance from people with
      schizophrenia.
AB  - OBJECTIVE: To examine the extent to which the public's desire for social distance
      from people with schizophrenia is influenced by beliefs about the disorder and
      stereotypes about those suffering from it. METHODS: In spring 2001, we carried
      out a representative survey of individuals of German nationality aged 18 years
      and over (n = 5025). Each subject was given a fully structured interview that
      began with the presentation of a vignette. RESULTS: Both labelling and beliefs
      about the disorder's causes and prognosis, as well as the perception that those
      suffering from it are unpredictable and dangerous, had an impact on the public's
      desire for social distance. However, the latter proved to be more important. As
      expected, respondents who identified the disorder depicted in the vignette as
      mental illness, those who blamed the individual for its development, and those
      who anticipated a poor prognosis expressed a stronger desire for social distance.
      Endorsing biological factors as a cause was also associated with increased social
      distance. CONCLUSIONS: Our findings have important implications for interventions
      aimed at reducing stigma and discrimination related to schizophrenia. Targeting
      the stereotype of unpredictability and dangerousness appears to be particularly
      important.

PMID- 14674049
TI  - Addiction: a disease of volition caused by a cognitive impairment.
AB  - The common etiology of substance and behavioural addictions is one that suggests
      faulty volition caused by a cognitive impairment. A cognitive impairment that
      minimizes the recall of the negative effects of the addictive behaviour is viewed
      as necessary and causal to all addictions. The proposed definition for addiction
      clarifies the confusion associated with addictive disorders, explains the many
      variable presentations, and provides an explanation of comorbidity and treatment
      outcomes. In addition, this paper suggests why this process has not been
      previously identified.

PMID- 14674050
TI  - Defining anxious depression: going beyond comorbidity.
AB  - OBJECTIVE: Since publication of the DSM-IV, there remains a group of patients
      with depression and anxiety symptoms who are not well classified. We therefore
      wanted to determine more accurately the type of patients best described by the
      term "anxious depression." We also wanted to review the literature to assess the
      most appropriate treatment(s) for these patients. METHOD: We surveyed the medical
      literature published after 1994 for all articles containing the relevant terms
      and assessed all possible articles in detail to determine those relevant to the
      diagnosis and those that involved relevant clinical studies. RESULTS: The term
      anxious depression can encompass 3 groups of patients: those with comorbid major
      depressive disorder (MDD) and an anxiety disorder, those with MDD but with
      subthreshold anxiety symptoms, and those with subthreshold depressive and
      subthreshold anxiety symptoms (also called mixed anxiety and depressive
      disorder). CONCLUSIONS: Based upon our literature review, we believe that the
      term anxious depression should only be used for the second group; that is, those
      patients with an MDD and subthreshold anxiety symptoms. From our literature
      review to determine the most appropriate treatment for this group of patients, it
      appears likely that drugs inhibiting the reuptake of both noradrenaline and
      serotonin may have greater clinical utility than single-action drugs such as the
      selective serotonin reuptake inhibitors (SSRIs). However, it is also clear that
      much more research needs to be undertaken in this important patient group so that
      we can better understand its prevalence, clinical features, and treatment.

PMID- 14674051
TI  - Psychiatric distress among road rage victims and perpetrators.
AB  - OBJECTIVE: To investigate the relation between psychiatric distress and road
      rage, paying particular attention to the potential link between psychiatric
      illness and frequent involvement in serious forms of road rage. METHOD: This
      study reports data on road rage involvement, demographic characteristics, and
      mental health for a representative sample of 2610 adults in Ontario. The mental
      health indicator was the 12-item General Health Questionnaire. RESULTS: A cluster
      analysis revealed 5 distinct groups of people affected by road rage. The most
      serious offenders (referred to hereafter as the hard core road rage group),
      representing 5.5% of those affected, exhibited frequent involvement in the most
      severe forms of road rage and were the most likely (27.5%) to report psychiatric
      distress. CONCLUSIONS: Road rage, particularly experiences of victimization, is
      related to psychiatric distress. Evidence of psychiatric distress was highest
      among hard core road rage perpetrators, individuals noted for frequent
      involvement in serious aggressive and violent conduct. Further research is needed
      on violence and road rage and its link to mental health.

PMID- 14674052
TI  - Risk of weight gain associated with antipsychotic treatment: results from the
      Canadian National Outcomes Measurement Study in Schizophrenia.
AB  - BACKGROUND: Antipsychotic-induced weight gain occurs in a substantial percentage
      of treated persons. There remains a paucity of naturalistic data that describe
      relative weight-gain liability with the available novel atypical antipsychotics
      (NAPs). This investigation describes comparative NAP-induced weight gain in a
      prospective naturalistic cohort of persons with schizophrenia and related
      psychotic disorders. METHODS: The Canadian National Outcomes Measurement Study in
      Schizophrenia (CNOMSS) is an ongoing prospective, longitudinal, naturalistic
      study involving 32 academic and community sites across Canada. Persons with DSM
      IV-defined schizophrenia, schizophreniform or schizoaffective disorder, and
      psychosis not otherwise specified were consecutively enrolled. The overarching
      objectives of this initiative were to collect and compare global effectiveness,
      tolerability, safety, and humanistic outcomes in persons receiving commercially
      available NAPs in Canada. This analysis reports only weight change with the
      respective NAPs. Other outcomes were reported in separate companion papers.
      RESULTS: A spectrum of weight-gain liability was noted with quetiapine (QUE)
      (mean 7.55 kg, SD 9.20; P = 0.28), olanzapine (OLZ) (mean 3.72 kg, SD 0.56; P =
      0.15), and risperidone (RIS) (mean 1.62 kg, SD 7.72; P = 0.43). Categorically
      defined weight gain (that is, over 7% of baseline weight) was observed in 55.6%
      of QUE patients, 24.1% of OLZ patients, and 23.7% of RIS patients. Adjusting for
      demographic and disease-specific confounding factors, QUE patients had greater
      odds of gaining over 7% of their baseline weight compared with RIS patients (odds
      ratio [OR] 3.62; 95% CI, 1.02 to 12.83; P = 0.05). No statistical difference was
      detected between OLZ patients and RIS patients for over 7% of baseline weight (OR
      1.54; 95% CI, 0.63 to 3.75; P = 0.12) or over 10% weight gain (OR 1.44; 95% CI,
      0.50 to 4.13; P = 0.58). CONCLUSION: Clinicians are reminded to monitor
      anthropometric and metabolic parameters in all NAP-treated persons. Clinically
      significant differences in weight gain liability exist among the available NAPs.

PMID- 14674053
TI  - An open-label study of nefazodone treatment of major depression in patients with
      congestive heart failure.
AB  - OBJECTIVES: To evaluate the feasibility of screening and recruiting patients with
      major depression and congestive heart failure (CHF) in a tertiary care cardiology
      hospital and to obtain preliminary efficacy, tolerability, and safety data for
      nefazodone treatment of a major depressive episode in CHF patients. METHOD: We
      conducted a 12-week, open-label trial of nefazodone given in dosages up to 600 mg
      daily. We assessed patients at baseline, 1, 2, 4, 8, and 12 weeks. Measures used
      were the 17-item Hamilton Depression Rating Scale (HDRS), the Clinical Global
      Impression Scale, the Beck Depression Inventory, Spielberger's State-Trait
      Anxiety Inventory, and the Minnesota Living with Heart Failure Questionnaire. We
      also obtained pre- and poststudy ECGs, 24-hour Holter monitor recordings, and
      plasma levels of norepinephrine. RESULTS: After screening 443 CHF patients, 28
      patients with major depression met study eligibility criteria. The 23 patients
      who completed 4 or more weeks of medication showed significant improvement on all
      depression scales and in quality of life. Of 19 subjects who completed the full
      12-week trial, 74% experienced a decline of 50% or more on HDRS scores. The
      completers also showed a significant reduction in heart rate, an increase in QT
      intervals (but not in the QTc), and a marginally significant decrease in plasma
      norepinephrine. There were no changes in heart rate variability. CONCLUSIONS: It
      is feasible to screen and recruit CHF patients with major depression for an anti
      depressant trial. Nefazodone seems sufficiently safe, tolerable, and efficacious
      to justify a larger, placebo-controlled trial.

PMID- 14674054
TI  - Subtypes of schizophrenia: a cluster analytic approach.
AB  - OBJECTIVES: To identify empirical subtypes of schizophrenia, based upon the
      symptoms recorded over the duration of the illness, and to validate the resulting
      clusters against other systems that are used for subtyping schizophrenia. METHOD:
      Data for 55 symptoms of schizophrenia over the history of the illness from 107
      chronic schizophrenia patients were analyzed using hierarchical cluster analysis
      with Euclidean distance and Ward's method. Except for 1 patient, all met DSM-III
      criteria. There were 40 men and 67 women, average (SD) age of 38.2 (9.91) years,
      with a mean (SD) hospitalization of 27.9 (27.35) months. RESULTS: No clear and
      unambiguous solution for the number of clusters was evident. Examination of the
      clusters led to further analysis of 2- and 6-cluster solutions. These were
      contrasted with DSM-III, DSM-III-R, and DSM-IV criteria and with the subtypes
      taken from the literature. There was limited support for any of these types, with
      none replicating, including the paranoid-nonparanoid distinction. CONCLUSIONS:
      Empirical clusters derived from lifetime symptom data failed to agree with either
      the established DSM or other empirically derived subtypes. Subtypes may have
      little utility when the variability of symptoms over the longitudinal course of
      the illness is considered.

PMID- 14674055
TI  - Bongs, a method of using cannabis linked to dependence.

PMID- 14674056
TI  - Obsessive-compulsive symptoms in schizophrenia induced by risperidone and
      responding to fluoxetine.

PMID- 14674057
TI  - Lengthy period of incarceration as personal treatment goal.

PMID- 14674058
TI  - Autoamputation in psychosis: diagnostic issues.

PMID- 14674059
TI  - A preliminary report on substance use patterns in an adolescent psychiatric
      population.

PMID- 14674060
TI  - Facialis palsy attributable to depot antipsychotic therapy.

PMID- 14674061
TI  - Recognizing complicated grief in clinical practice.

PMID- 14674062
TI  - Splenic fine needle aspiration and core biopsy. A review of 49 cases.
AB  - OBJECTIVE: To analyze the authors' experience with splenic fine needle aspiration
      (sFNA) and splenic core biopsy (sCB) and to examine their roles in patients with
      splenomegaly or splenic mass lesions. STUDY DESIGN: A total of 56 sFNAs and/or
      sCBs were performed on 49 patients for neoplastic and nonneoplastic indications.
      Both sFNAs and sCBs were performed in 21 (38%) cases, sFNAs alone in 26 (46%) and
      sCBs only in 9 (16%). Cytologic findings were evaluated for specimen adequacy,
      diagnosis and use of ancillary techniques. Cytologic diagnosis was compared with
      histology on subsequent splenectomy or bone marrow biopsy, when available.
      RESULTS: There were a total of 33 males and 16 females (aged 30-82 years) in the
      study. Radiologic findings were single or multiple masses (42), fluid collection
      (3) or diffuse splenomegaly (4). The cytologic diagnosis was neoplastic process
      in 12 (25%), nonneoplastic in 32 (65%) and inadequate specimen in 5 (10%). The
      procedure was adequate for diagnosis in 44 (90%) patients. Cytologic diagnosis
      correlated with subsequent histology in all cases where tissue diagnosis was
      available. Major complications occurred in 3 (6%) patients, including hemorrhage,
      pseudoaneurysm and hypotension. Five other patients (10%) had minor
      complications. The number of passes, inclusion of sCB and repeat procedures were
      not associated with an increased risk of complications. CONCLUSION: sFNA and sCB
      have excellent diagnostic accuracy in both neoplastic and nonneoplastic splenic
      disorders. While the overall complication rate is significant, major
      complications of the procedure are uncommon.

PMID- 14674063
TI  - Exploring the links between quality assurance and laboratory resources. An audit
      based study.
AB  - OBJECTIVE: To investigate and rectify the problems related to Ziehl-Neelsen (Z-N)
      staining in a cytology laboratory in the context of quality assurance. STUDY
      DESIGN: An audit based quality assurance study of 1,421 patients with clinical
      diagnoses of tubercular lymphadenopathy who underwent fine needle aspiration
      cytology. Data from 8 months were audited (group 1). Laboratory practices related
      to selection of smears for Z-N staining were studied. A 2-step corrective measure
      based on results of the audit was introduced for 2 months (group 2). Results were
      subjected to statistical analysis using the chi 2 test. RESULTS: Of 1,172
      patients in group 1,368 had diagnoses other than tuberculosis. Overall acid-fast
      bacillus (AFB) positivity was 42%. AFB positivity in 249 patients in group 2 was
      89% (P < .0001). CONCLUSION: Several issues in the laboratory are linked to
      quality assurance. Solving everyday problems can have far-reaching benefits for
      the performance of laboratory personnel, resources and work flow.

PMID- 14674064
TI  - Cytologic findings with histologic correlation in 43 cases of mammary intraductal
      adenocarcinoma diagnosed by aspiration biopsy.
AB  - OBJECTIVE: To review the cytologic and subsequent histologic findings in
      intraductal mammary adenocarcinoma (ductal adenocarcinoma in situ) (DCIS) to
      evaluate the role of aspiration biopsy (AB) in identifying and grading the
      disease. STUDY DESIGN: AB smears and tissue sections from 43 women with pure DCIS
      who underwent preoperative AB were reviewed. Smears were assessed for
      cellularity, cellular arrangement (including dissociation, nuclear size and
      pleomorphism), and presence of nucleoli and necrosis. RESULTS: Of the 43 cases,
      22 were high grade (HG) DCIS, 7 cases were intermediate grade (IG), and 14 cases
      were low grade (LG). Cytologic findings of HG DCIS was as follows: high
      cellularity (22/22), clusters of pleomorphic cells with large nuclei and
      increased nuclear/cytoplasmic ratios (22/22), single cells (20/22), prominent
      nucleoli (22/22) and necrosis (diffuse in 15/22, focal in 7/22). All LG cases had
      moderately to highly cellular smears with cohesive, 3-dimensional sheets of
      uniform, small cells with inconspicuous nucleoli arranged around a central lumen,
      forming "punched-out" spaces. Single cells were prominent in 2 of 14 cases. IG
      DCIS showed intermediate features between LG and HG DCIS: 3-dimensional sheets
      with punched-out spaces, abundant single cells, moderate pleomorphism and focal
      necrosis. CONCLUSION: HG DCIS is easily identifiable on AB smears; however,
      distinction from invasive carcinoma may not be possible. The cytologic diagnosis
      of LG DCIS is difficult, and 50% of our cases were called atypical on AB.
      Recognition of cohesive cellular arrangements with crowding and punched-out
      spaces is crucial as single cells and prominent atypia are often lacking.

PMID- 14674065
TI  - Accuracy and consistency in application of a probabilistic approach to reporting
      breast fine needle aspiration.
AB  - OBJECTIVE: To determine the application of a probabilistic/categorical approach
      for reporting breast fine needle aspiration (FNA) and its dependence on the
      cytopathologist's level of experience. STUDY DESIGN: All breast surgical
      specimens that had preoperative breast FNA at our institution during a 3-year
      period were identified. The cytologic results were reported as 1 of 6 categories:
      positive, suspicious, atypical, epithelial proliferative, unremarkable and
      nondiagnostic, according to well-defined criteria. Five cytopathologists were
      responsible for all cytology sing-out during the study period. The histologic and
      cytologic diagnoses were correlated. RESULTS: A total of 297 cases were
      identified. Overall, there were no false positive cases (positive predictive
      value [PPV] = 100%). Two false negative cases (negative predictive value [NPV] =
      96%) were due to sampling error. This indicates that the PPV and NPV for each of
      the 5 pathologists were also all 100% except for the 1 pathologist who had two
      false negative cases due to sampling errors. The probability of finding carcinoma
      on histology for suspicious and atypical cytologic categories ranged from 67% to
      100% and 8% to 31%, respectively, for the individual pathologists. Fifteen cases
      were signed out by > or = 2 pathologists. The involvement of consultants was
      significantly associated with diagnosis (P = .02). Ten of the 15 cases were in
      the suspicious (5) or atypical (5) category. CONCLUSION: The probabilistic
      approach with defined diagnostic criteria is an accurate method and can be
      consistently applied in reporting breast FNA. Although use of the indeterminate
      (suspicious and atypical) categories is variable, a definite and considerable
      difference in the probability of carcinoma between these 2 categories was
      observed for all pathologists. The involvement of consultants did not move the
      cases out of these indeterminate categories.

PMID- 14674066
TI  - Assessment of thin-layer breast aspirates for immunocytochemical evaluation of
      HER2 status.
AB  - OBJECTIVE: To determine whether immunocytochemistry (ICC) for HER2 on ThinPrep
      (TP)-processed breast fine needle aspiration biopsies (Cytyc Corp., Boxborough,
      Massachusetts, U.S.A.) is comparable to the findings of immunohistochemistry on
      corresponding surgically removed tissue. STUDY DESIGN: Immunostaining was
      performed on 63 malignant breast fine needle aspirates and compared to
      immunostaining on paraffin sections (PSs) from the subsequent biopsies. The
      HercepTest (Dako, Carpinteria, California, U.S.A.) and TAB250 antibodies were
      utilized. Cases in which the TP and paraffin HER2 results did not correlate were
      further assessed for gene amplification by differential polymerase chain reaction
      (dPCR). RESULTS: HER2 overexpression was found in 9 of the 63 cases (14%). TAB250
      had higher specificity on PS versus TP (P = .008), and TAB250 had higher
      specificity on PS versus the HercepTest on PS and TP (P = .004 and .0001,
      respectively). CONCLUSION: HER2 immunostaining with both the HercepTest and
      TAB250 on TP is unreliable due to low specificity (72% and 83% for HercepTest and
      TAB250, respectively). However, both antibodies have high sensitivity (89% and
      100%, respectively); suggesting that this method may have some utility as a
      preliminary screening test for HER2 status. Negative HER2 staining by ICC is
      highly predictive of the absence of HER2 overexpression, whereas positive HER2
      staining on TP would require further validation by either dPCR of fluorescence in
      situ hybridization.

PMID- 14674067
TI  - Sequence analysis of the JC virus transcriptional control region detected in
      urine from HIV-positive patients.
AB  - OBJECTIVE: To investigate the correlation between transcriptional control region
      (TCR) types and virus replication and the role of decreased host immunity in
      inducing TCR changes. STUDY DESIGN: In a previous study, urine specimens from 78
      unselected HIV-positive patients were independently evaluated by cytology,
      immunohistochemistry and nested polymerase chain reaction (n-PCR) to detect the
      presence of polyomaviruses. The JC virus (JCV) large T region was positive in
      44/78 (56%) urine specimens by n-PCR. In the current study, these cases further
      underwent to n-PCR to detect TCR, and the amplified products were sequenced. The
      JCV types identified were compared using: (1) morphologic evidence of replication
      (decoy cells and/or immunohistochemical staining of cells detected using anti-SV
      40 antiserum), and (2) patients' immune status (CD4+ cell counts). RESULTS: TCR
      was successfully amplified in 30/44 cases (68%). TCR sequence analysis disclosed
      6/30 archetype (20%) and 24/30 archetypelike sequences, the latter distributed as
      follows: 4 G2 (4/30, 13%) with G-->A substitutions in the C sequence (nt 9), and
      20 CY (20/30, 67%) with A-->G substitutions in the F sequence (nt 19). There were
      no correlations with morphologic evidence of viral replication or immune status.
      CONCLUSION: The present study indicated that TCR in urine samples from PML-free
      HIV-positive subjects are archetypes or archetypelike. Immune suppression does
      not seem to influence minor changes in the TCR genome, and single by mutations do
      not change JCV replication activity.

PMID- 14674068
TI  - CIN 2/3 and cervical cancer after an ASCUS pap smear. A 7-year, prospective study
      of the Norwegian population-based, coordinated screening program.
AB  - OBJECTIVE: To estimate the risk of being diagnosed with cervical intraepithelial
      neoplasia (CIN) 2/3 or invasive cervical cancer (ICC) based on diagnostic and
      screening procedures performed after a diagnosis of atypical squamous cells of
      undetermined significance (ASCUS) and to compare this risk to that in women with
      a normal Pap smears. STUDY DESIGN: A 7-year, prospective, cohort study was
      performed in the Norwegian population-based, coordinated screening program. After
      excluding women in the midst of follow-up of an abnormal Pap smear or with a
      history of CIN 2/3 or ICC, the study population consisted of women 25-69 years of
      age with a normal (n = 526,661) or ASCUS Pap smear (n = 10,037) in 1995-1996.
      Risk estimates were calculated by logistic and parametric survival regression.
      RESULTS: Within 7 years of an ASCUS smear, 1,017 women (10.1%) were diagnosed
      with CIN 2/3 and 62 (0.62%) with ICC. Women with an ASCUS index Pap smear had a
      relative risk of 15-30 of being diagnosed with histologically verified CIN 2/3 or
      ICC within the first 2 years of follow-up as compared to women with a normal
      index smear. In long-term follow-up, women with an ASCUS index smear followed by
      a normal smear, which cancelled further clinical follow-up, were at > 3.5 times
      higher risk of both CIN 2/3 and invasive cancer as compared to women with a
      normal index smear. CONCLUSION: Pap smear follow-up of women with an ASCUS smear
      does not identify all women at higher risk of CIN 2/3 and ICC. Other diagnostic
      procedures should be implemented to improve the screening program.

PMID- 14674069
TI  - Cytomorphology and histomorphology after thermal endometrial ablation. Early
      changes.
AB  - OBJECTIVE: Endometrial thermal balloon ablation is a recent technique for
      treatment of dysfunctional uterine bleeding. Although the histologic features of
      thermal injury to the endometrium have been documented, the cytologic features
      are not described in the literature. In this study, the cytomorphology of recent
      thermal injury was studied and correlated with histomorphology. STUDY DESIGN: The
      study consisted of 29 cases divided into 3 groups: (1) control group,
      hysterectomies without ablation; (2) specimen (in vitro) group, where ablation
      was carried out on the uteri in the immediate postoperative period; and (3) in
      vivo group, with intraoperative endometrial ablation. The cytotoxic effect of
      thermal injury was assessed by staining the smears for oxidative enzymes.
      RESULTS: The cytomorphologic features of in vivo thermal ablation were
      characteristic and composed of fragmented glands, numerous single cells with
      fuzzy cytoplasm and giant cells. Staining for dehydrogenases was absent from >
      90% of endometrial cells in the in vivo cases as against 100% positivity in the
      control group. CONCLUSION: The cytomorphologic features described for the first
      time in this study can be applied to endometrial aspirate or brush smears to
      evaluate the efficacy of the technique and follow-up.

PMID- 14674070
TI  - Prevalence and typing of HPV DNA in atypical squamous cells in pregnant women.
AB  - OBJECTIVE: To determine the prevalence and typing of HPV DNA in pregnant women
      with a diagnosis of atypical squamous cells (ASC) and to assess whether pregnancy
      related changes contribute to the diagnosis of ASC. STUDY DESIGN: HPV testing was
      performed on residual specimens from the ThinPrep Pap test (Cytyc Corp.,
      Boxborough, Massachusetts, U.S.A.) in pregnant women diagnosed as ASC (study
      group, n = 105), low and high grade squamous intraepithelial lesion (LSIL and
      HSIL) (positive control, n = 33) and negative for epithelial cell abnormality
      (negative control, n = 20). All cases were reviewed by 2 cytopathologists to
      obtain consensus diagnoses using the Bethesda System 2001 criteria. The study
      group cases were further subcategorized into ASC of undetermined significance
      (ASCUS, n = 99) and ASC cannot exclude HSIL (ASC-H, n = 6). HPV testing was also
      performed on an ASC control group consisting of 68 consecutive ASC cases in
      nonpregnant women, matched by age. RESULTS: Mean patient age was 23.7 years for
      the study group and 25.6 years for the ASC control group. HPV DNA was detected in
      88.6% of cases in the study group, including 87.9% of ASC-US and 100% of ASC-H
      cases. Of the HPV positive cases, 79.6%, 4.3%, 5.4% and 10.8% had high-risk,
      mixed high- and low-risk, low-risk and unknown HPV types, respectively. The most
      frequent HPV types detected were: types 52 (31.2%), 16 (15.1%), 39 (11.8%), 53
      (10.8%), and 18 and 58 (9.7% each). Multiple viral types were detected in 43.0%
      of cases. The prevalence of HPV DNA in the positive and negative controls in
      pregnant women was 100% and 55%, respectively. HPV DNA was detected in 83.8% of
      the ASC control group. CONCLUSION: Regardless of pregnancy-related changes, the
      prevalence of HPV DNA in pregnant women (88.6%) was similar to that found in ASC
      in nonpregnant women of the same reproductive-age group (83.8%), and the high
      risk types accounted for the vast majority of cases (83.9%). These findings
      demonstrate that pregnancy-related changes do not contribute to the diagnosis of
      ASC in this subset of women. Furthermore, the high HPV DNA prevalence in
      reproductive-age women (< 40 years) suggests that HPV testing may have limited
      utility in effective management of these patients.

PMID- 14674071
TI  - Bronchial cytology in pleural mesothelioma. A report of 3 positive cases,
      including 1 diagnosed initially on bronchial brushings.
AB  - OBJECTIVE: To evaluate retrospectively the value of bronchial aspiration cytology
      in patients with histologically proven pleural mesothelioma, reappraising
      positive smears in light of conventional microscopic features and, when feasible,
      immunocytochemical investigations. STUDY DESIGN: In 3 cases of mesothelioma with
      bronchial brushings positive for malignant cells, the cytologic features were
      correlated with the histologic findings. RESULTS: Salient microscopic features
      included scant to moderate cellularity arranged in micropapillary clusters,
      morular aggregates with scalloped borders and isolated malignant cells.
      Intercellular clear spaces or windows suggesting a brush border on cell membranes
      were also noted. In cases with available material, immunocytochemistry was
      positive for keratins, epithelial membrane antigen and calretinin and negative
      for carcinoembryonic antigen. All the cases were histologically confirmed
      epithelial mesotheliomas. CONCLUSION: In rare cases, pleural mesothelioma cells
      are shed within the airway lumina and can be detected in bronchoscopic cytology
      specimens. Cytologic features seem comparable to their analogues in pleural
      effusions. Although no single criterion appears diagnostic, their combined
      documentation could ensure correct interpretation, especially if supported by a
      limited immunocytochemical panel.

PMID- 14674072
TI  - Sputum cytology for the diagnosis of lung cancer. Comparison of smear and
      modified cell block methods.
AB  - OBJECTIVE: To compare the sputum smear cytology and cell block methods for
      specimen adequacy, cytology quality and diagnostic accuracy in the diagnosis of
      lung cancer. STUDY DESIGN: We assessed 2,524 sputum specimens from 768 patients.
      The specimens were prepared as smears and cell blocks for cytopathologic
      examination between March 1, 1992, and December 31, 1998. The smear and cell
      block slides were evaluated both separately and together, and the results were
      compared with radiologic and histopathologic diagnoses. RESULTS: The sensitivity
      of the smear method was 69.4% and specificity was 99.5%. The sensitivity of the
      cell block method was 84.4% and specificity, 100%. The sensitivity of the smear
      and cell block together was 87.6% and specificity, 99.5%. CONCLUSION: The cell
      block method increases the sensitivity and specificity of sputum cytology, and
      when smear and cell block slides are evaluated together, sensitivity reaches its
      highest value. Therefore, application of smear and cell block methods together
      seems most useful in the diagnosis of lung cancer.

PMID- 14674073
TI  - Intraoperative cytologic diagnosis of sentinel node metastases in breast cancer.
AB  - OBJECTIVE: To clarify the usefulness of imprint cytology for intraoperative
      investigations of sentinel lymph nodes in breast cancer, comparing the results
      with those of examinations using frozen and permanent sections. STUDY DESIGN: The
      material consisted of 303 sentinel lymph nodes from 124 cases of clinically node
      negative breast cancer. Touch imprint cytologic slides and frozen sections were
      obtained from the same cut surface of the sentinel nodes. Correlations with the
      final histopathologic results in paraffin sections were evaluated. RESULTS: The
      sensitivity, specificity and accuracy of imprint cytology were 70.3%, 99.6% and
      96.0%, and those of frozen sections were 83.8%, 100%, 98.0%, respectively. The
      values were improved when the 2 methods were combined (89.2%, 99.6%, 98.3%),
      though the concordance between imprint cytology and frozen section was 91.9%.
      CONCLUSION: Both imprint cytology and frozen section are useful for evaluating
      sentinel lymph node status in breast cancer. However, the 2 techniques should be
      combined to improve the diagnostic sensitivity.

PMID- 14674075
TI  - Evaluation of a centrifuge method and thin-layer preparation in urine cytology.
AB  - OBJECTIVE: To evaluate and compare the quality and cost of urine cytology using
      the Cytospin method (Shandon, ThermoElectron Corporation, Waltham, Massachusetts,
      U.S.A.) and the AutoCyte PREP (TriPath Imaging, Burlington, North Carolina,
      U.S.A.) in a general laboratory. STUDY DESIGN: A study of differences between the
      Cytospin method and AutoCyte PREP in the areas of specimen preparation, staining,
      number and quality of diagnostic cells, background, screener preference, and cost
      was undertaken over a 3-month period in 2000. Sixty fresh voided urine samples
      from 25 patients with known transitional cell carcinoma were prepared by the
      Cytospin method and the AutoCyte PREP according to the manufacturers'
      instructions. RESULTS: The Cytospin method had longer preparation time but
      shorter screening time than the AutoCyte PREP. The number of diagnostic cells was
      higher in the Cytospin method. Fixation quality and staining clarity were better
      in the Cytospin method. Qualitative assessment of cell arrangements, cell and
      nuclear size and shape, nuclear/cytoplasmic ratio and nuclear membrane
      irregularity showed no significant differences between the 2 methods. Cellular
      details and nuclear chromatin patterns were clearer and better preserved in the
      Cytospin method, but the AutoCyte PREP showed less blood and inflammatory cells
      and debris. CONCLUSION: In the majority of cases the screeners preferred the
      Cytospin method due to its better overall cytologic quality. However, the amount
      of blood, inflammation and debris was much lower in the AutoCyte PREP. This
      reduced the need to make a second, diluted specimen and made turnaround time
      faster. The AutoCyte PREP was 7 times more expensive than the Cytospin method.

PMID- 14674074
TI  - Vimentin and leukocyte common antigen-negative molding cells in pleural effusions
      of patients with small cell lung carcinoma.
AB  - OBJECTIVE: To determine whether the presence of vimentin and leukocyte common
      antigen (LCA)-negative molding cells (VLNMC) could help in identifying rare small
      cell lung carcinoma (SCLC) cells. STUDY DESIGN: Thirty-four cell blocks of
      pleural effusions (PEs) from 26 patients with confirmed SCLC were stained
      immunohistochemically with vimentin and LCA antibodies and compared with
      hematoxylin and eosin-stained preparations. RESULTS: VLNMC were present in 22/22
      PEs originally diagnosed as positive or atypical/suspicious for SCLC. Focal
      vimentin staining was seen in SCLC in 10/22 cases, and 1 case showed many
      vimentin-positive SCLC cells. One of 11 PEs originally interpreted as negative
      showed rare groups of VLNMC. This was supported by a subsequent PE obviously
      positive for SCLC. CONCLUSION: Immunoperoxidase stains for vimentin and LCA
      highlight SCLC in PEs as VLNMC; however, morphologic criteria must prevail in
      making the final diagnosis.

PMID- 14674076
TI  - Alternative, cost-effective fungus-staining method for control slides in cytology
      and histopathology.
AB  - OBJECTIVE: To develop a cost-effective, reliable and safe method of providing
      fungal control slides for routine use in pathology laboratories. STUDY DESIGN: A
      set of easily available, low-cost material was tested to obtain fungal colonies
      on substrate adequate for paraffin-embedded sections or smears. RESULTS: Such
      material as cheese is a simple, inexpensive and practical culture medium for
      silver-positive fungi. A batch of paraffin blocks can be prepared to maintain a
      stock of control material in the laboratory. CONCLUSION: It is useful to maintain
      fungal colonies to produce staining control specimens using small pieces of
      refrigerated cheese to easily produce silver-staining control specimens or smears
      embedded in paraffin, reducing the risk of accidental exposure to potentially
      infective pathogens in the laboratory. This method might also be a good
      alternative for conserving routine surgical specimens, considering the currently
      decreasing numbers of necropsy and large specimens, particularly from
      immunosuppressed and infected patients.

PMID- 14674077
TI  - Mammary mucinous carcinoma with marked cytoplasmic hyalinization. A report of 2
      cases with emphasis on fine needle aspiration cytologic findings.
AB  - BACKGROUND: Cytoplasmic eosinophilia in breast tumors is due mainly to abundance
      of secretory granules, lysosomes and/or mitochondria. Diffuse cytoplasmic
      hyalinization caused by intermediate filaments has not been described before.
      CASES: Two cases of pure mammary mucinous carcinoma occurred with marked
      cytoplasmic hyalinization among 556 wide excision/mastectomy specimens of mammary
      ductal carcinoma, either in situ or invasive, encountered at Pamela Youde
      Nethersole Eastern Hospital, Hong Kong, during the period from 1994 to the end of
      2001. Preoperative fine needle aspiration cytology was available in 1 case,
      showing cohesive clusters and micropapillae of tumor cells in abundant background
      mucin. The tumor cells had low mitotic activity and possessed round to oval
      nuclei, solitary macronucleoli; ample, eosinophilic cytoplasm and discrete cell
      borders. Cytoplasmic granularity, intracytoplasmic vacuoles or "cometlike" cells
      were not found. Histologic examination of the surgical specimens in both cases
      revealed pure mucinous carcinoma with diffuse and marked cytoplasmic
      hyalinization. There was no evidence of peritumoral lymphovascular permeation or
      regional lymph node metastasis. Ultrastructural examination showed minimal
      secretory activity, with abundant, loose aggregates of intermediate filaments in
      the cytoplasm. There was a relative paucity of other organelles. CONCLUSION:
      Diffuse cytoplasmic hyalinization is a peculiar morphologic change in mammary
      ductal carcinoma and apparently unique to pure mucinous carcinoma. Recognition of
      this phenomenon may help to avoid misdiagnosis of other types of ductal carcinoma
      with cytoplasmic eosinophilia, such as apocrine carcinoma and ductal carcinoma
      with neuroendocrine differentiation, which sometimes are also associated with
      pools of extracellular mucin.

PMID- 14674078
TI  - Cytomorphology of verrucous carcinoma of the cervix. A case report.
AB  - BACKGROUND: Verrucous carcinoma of the uterine cervix is rare. Cytology is
      thought not to be helpful in the diagnosis of this lesion due to its bland
      morphology. The cytologic features of this lesion remain poorly defined. CASE:
      The cytologic findings in a Pap smear facilitated the diagnosis of verrucous
      carcinoma of the cervix. The features included atypical polygonal and spindle
      cells with abundant, keratinizing cytoplasm; atypical squamous cells with pearl
      formation; and frequent, nonkoilocytic cytoplasmic vacuolization. CONCLUSION:
      There are 30 published reports on verrucous carcinoma involving the cervix and
      vagina that include the cytologic findings. In 70% of these cases, cytology was
      abnormal. Recognition of the cytologic characteristics may help in identifying
      this lesion on cytology, prevent delays in diagnosis and ensure that patients
      receive appropriate therapy.

PMID- 14674079
TI  - Cytologic profile of rhabdoid tumor of the kidney. A report of 3 cases.
AB  - BACKGROUND: Malignant rhabdoid tumor of the kidney (MRTK) is a rare malignant
      neoplasm that usually presents as an abdominal mass. The histogenesis is
      uncertain, and cases outside the kidney have been reported. An association with
      separate primary tumors of primitive neuroepithelial origin occurring in the
      midline of the posterior or middle cranial fossa has been reported in
      approximately 15% of cases. CASES: Three patients, a 7-month-old girl and two
      boys, aged of 6 and 2 months of age, underwent fine needle aspiration biopsy
      (FNAB) for the diagnosis of renal masses. In 2 cases the smears revealed round to
      polygonal cells, singly or arranged in irregularly shaped clusters. The
      neoplastic cells did not differ much in shape and exhibited clear, empty nuclei
      with prominent nucleoli; the cytoplasm was abundant and sometimes eosinophilic.
      In the remaining case the aforementioned characteristics of the nuclei and
      cytoplasm were not as prominent, and sheets of fibrovascular stroma, with
      attached neoplastic cells, were seen. Diagnosis of MRTK was suspected in every
      case based upon morphology and immunocytochemistry; the diagnosis was
      histologically confirmed in the surgical specimens. CONCLUSION: MRTK may pose
      diagnostic problems due to its broad morphologic spectrum. Distinction from
      Wilms' tumor and clear cell sarcoma of the kidney is essential for therapeutic
      proposes. The results obtained in the FNAB study of these 3 cases demonstrate
      that diagnosis of MRTK may be proposed from fine needle aspiration smears using
      conventional methods together with ancillary ones (immunocytochemistry and
      electron microscopy).

PMID- 14674080
TI  - Fine needle aspiration cytology of an ovarian luteinized follicular cyst
      mimicking a granulosa cell tumor. A case report.
AB  - BACKGROUND: Fine needle aspiration is a valuable tool in the diagnosis of ovarian
      cysts, especially in the young and when a nonneoplastic cyst is suspected. High
      cellularity, epitheliallike clusters and cellular atypia in aspirates from
      functional cysts are known features that may lead to an erroneous diagnosis of
      malignancy. Granulosa cells in ovarian cystic fluids may originate in follicular
      cysts or cystic granulosa cell tumors. In luteinized follicular cysts the cells
      usually have ample cytoplasm and tend to form clusters. This report draws
      attention to a case where abundant, dispersed cells lacking cytoplasm led to the
      incorrect diagnosis of a granulosa cell tumor. CASE: In an ovarian cystic
      aspirate from a 34-year-old woman, the fluid was highly cellular, with a striking
      predominance of cells interpreted as granulosa cells. Granulosa cells are often
      found in aspirates from functional cysts, but striking cellularity, prominent
      nuclear grooves and lack of luteinization made us consider a granulosa cell tumor
      rather than a follicle-derived cyst. Surgery was performed, and histology
      revealed a benign serous cystadenoma but also numerous maturing follicles and
      follicular cysts with thick layers of granulosa cells. The aspirate obviously did
      not represent the cystadenoma but one of the prominent follicular cysts.
      CONCLUSION: An understanding of the cytologic features of functional ovarian
      cysts, including the pitfalls, is necessary to avoid a false diagnoses of a
      neoplastic lesion. For a correct interpretation of the cytologic findings, close
      communication with the clinician and with the radiologist performing the
      aspiration is of vital importance.

PMID- 14674081
TI  - Nodal presentation of nasal-type NK/T-cell lymphoma. Report of two cases with
      fine needle aspiration cytology findings.
AB  - BACKGROUND: Epstein-Barr virus (EBV)-associated NK/T-cell lymphoma typically
      occurs in extranodal sites, such as nasal cavity, nasopharynx, gastrointestinal
      tract, skin, testis and salivary gland. Secondary lymph node involvement is
      rarely encountered until late in the disease course. The fine needle aspiration
      cytology of NK/T-cell lymphoma with a nodal presentation has not been described
      before. CASES: Two cases of nasal-type (extranasal) NK/T-cell lymphoma with a
      nodal presentation were seen at Pamela Youde Nethersole Eastern Hospital, Hong
      Kong. Both patients presented with submandibular lymph node enlargement but
      unremarkable peripheral blood and bone marrow findings. Fine needle aspiration
      cytology was available in both cases, showing a heterogeneous population of small
      to medium-sized lymphoid cells, follicular center cells, plasma cells,
      eosinophils and some histiocytes. The medium-sized lymphoid cells showed readily
      discernible nuclear atypia with an irregular nuclear outline. Cell block sections
      revealed occasional lymphoid cells with pleomorphic nuclei. Immunocytochemical
      study confirmed the presence of CD56-positive lymphoma cells. In situ
      hybridization for EBV-encoded RNA also revealed positive nuclear signals.
      Histologic examination of the surgical biopsies showed interfollicular expansion
      by malignant lymphoid cells. Immunoglobulin heavy chain gene and T-cell receptor
      gene rearrangement studies demonstrated a germline pattern, confirming the
      putative NK (natural killer cell), non-B and non-T lineage of the lymphoma cells.
      CONCLUSION: Nodal presentation of NK/T-cell lymphoma, though rare, is diagnosable
      on the basis of fine needle aspiration biopsy alone, especially in view of its
      distinctive immunophenotype and EBV association. Recognition of the subtle but
      definite cytologic atypia of malignant lymphoid cells and presence of an
      appropriate background (including more eosinophils than usual), together with
      proper application of ancillary techniques, is crucial to arriving at a correct
      diagnosis.

PMID- 14674083
TI  - Oral metastasis of breast carcinoma diagnosed by fine needle aspiration cytology.
      A case report.
AB  - BACKGROUND: Fine needle aspiration cytology (FNAC) is an important technique in
      the diagnosis of oral and maxillofacial conditions. The purpose of the present
      paper is to report a case of oral metastasis of breast carcinoma diagnosed by
      FNAC. CASE: A 45-year-old, black woman was referred for evaluation of symptomatic
      swelling in the left mandible. The medical history revealed that the patient had
      undergone extensive surgery to remove a lobular carcinoma. She had finished
      chemotherapy treatment about 5 months earlier. Due to the main diagnostic
      considerations of metastatic and inflammatory disease, FNAC was performed. The
      cytologic picture was consistent with a metastatic glandular neoplasm.
      CONCLUSION: FNAC is a safe, reliable, cost-effective and easy procedure and
      sometimes eliminates the need for open biopsy.

PMID- 14674082
TI  - Papillary clusters as a diagnostic pitfall in urinary cytology of
      pseudosarcomatous fibromyxoid tumor of the bladder. A case report.
AB  - BACKGROUND: Pseudosarcomatous fibromyxoid tumor (PFT) of the urinary bladder is
      an uncommon benign lesion that can involve any site in the bladder. Cellular
      features of PFT of the bladder are exceedingly rare. We describe the urinary
      cytology in a PFT patient who displayed numerous papillary fragments that
      suggested a malignant tumor. CASE: A 52-year-old man was seen at the hospital for
      evaluation of gross hematuria. At cystoscopy, the urologist observed a 3-cm,
      smooth, polypoid and ulcerated mass extending from the trigone to the bladder
      neck. Urinary cytology showed many papillary clusters with irregular nuclear
      margins in the bloody cell background. No spindle cells were noted. Cytology was
      interpreted as papillary growth, factor transitional cell carcinoma, grade 2-3. A
      laparotomy with partial resection of the urinary bladder was carried out, and
      histologically the tumor was composed of spindle, stellate, fibroblastic cells
      embedded in myxoid stroma with little collagen. Immunohistochemical and
      ultrastructural studies revealed the fibroblastic nature of the lesion. The final
      diagnosis was PFT of the bladder on the basis of histologic examination of the
      resected material. CONCLUSION: Papillary fragments are a diagnostic pitfall in
      urinary cytology of PFT lesions.

PMID- 14674084
TI  - Inflammatory myofibroblastic tumor of the breast. A case report.
AB  - BACKGROUND: Inflammatory myofibroblastic tumor (IMT) of the breast is a very rare
      tumor like lesion with only 6 previously reported cases. Very little is known
      about the cytology of IMT. We present the fine needle aspiration (FNA) cytology
      of a case of recurrent, bilateral IMT of the breast and detail the clinical
      course, radiologic findings, morphologic appearances and immunohistochemical
      profile of the lesion. CASE: A 79-year-old female was initially seen in 1991
      because of a suspicious mammographic abnormality in her right breast. Ultrasound
      guided FNA cytology showed an unusual "inflammatory" lesion with occasional
      aggregates of cellular connective tissue fragments, sheets of uniform ductal
      epithelial cells with myoepithelial cells, spindle cells, lymphocytes and
      histiocytelike cells. The lesion was excised, and histology confirmed a benign
      process with spindle cells, lymphocytes and histiocytes. No malignant features
      were noted. During follow-up many new lesions appeared in both breasts, and after
      several FNA procedures and local excisions, bilateral mastectomy was performed at
      the patient's urging. She remained disease free. CONCLUSION: Although IMT of the
      breast has benign cytology and histology, clinically and on imaging, it resembles
      carcinoma. Awareness of the condition may help prevent a false diagnosis of
      carcinoma.

PMID- 14674085
TI  - Pitfalls in fine needle aspiration cytology of extraadrenal paraganglioma. A
      report of 2 cases.
AB  - BACKGROUND: Fine needle aspiration (FNA) is commonly used as an initial
      diagnostic tool in the evaluation of mass lesions. However, extraadrenal
      paragangliomas (EAPs) are not commonly seen on FNA and, when encountered, can
      pose a diagnostic challenge since they have a wide variety of morphologic
      patterns. CASES: Two intraabdominal EAPs were misdiagnosed as an anaplastic
      adenocarcinoma of the pancreas with giant cell features and papillary
      adenocarcinoma of the pancreas. The sources of the pitfalls were inaccurate
      radiologic localization, misinterpretation of vascular-rich tissue fragments as
      papillary structures, presence of acinarmicroglandular structures, marked
      cellular pleomorphism (including multinucleation), prominent nucleoli and some
      cells with "squamoid" cytoplasm. CONCLUSION: The cytologic features of EAP,
      although suggestive, are not specific. A high index of suspicion and knowledge of
      clinical information, exact anatomic location and cytologic morphology combined
      with appropriate ancillary studies are the key to an accurate diagnosis.

PMID- 14674086
TI  - Gallbladder carcinoma cells in cerebrospinal fluid as the first manifestation of
      a tumor. A case report.
AB  - BACKGROUND: Meningeal carcinomatosis (MC) rarely occurs as the first evidence of
      a tumor. In such cases cytology of the cerebrospinal fluid is crucial to the
      diagnosis. The most frequent primary MCs are lung and breast cancers. MC from a
      gallbladder carcinoma is uncommon. CASE: A 58-year-old woman presented with
      paroxysmal headaches, seizures and coma. Analysis of the cerebrospinal fluid
      revealed carcinoma cells and a low protein concentration. Only postmortem
      examination discovered gallbladder adenocarcinoma to be the source of the tumor
      cells. CONCLUSION: A case with the onset of MC secondary to rare mucinous
      adenocarcinoma of the gallbladder is presented. Cytology of the cerebrospinal
      fluid was the only examination that uncovered malignancy. Nine similar cases were
      found in the literature. Low cerebrospinal fluid protein seems to be of
      diagnostic value.

PMID- 14674087
TI  - Crush cytology of melanocytoma of the spinal cord. A case report.
AB  - BACKGROUND: Primary melanocytic neoplasms of the central nervous system are rare.
      There is no previous report on the intraoperative crush cytology of these
      neoplasms. CASE: A melanocytoma occurred in a 65-year-old woman who presented
      with back pain, and weakness and numbness of the right lower extremity. Magnetic
      resonance imaging revealed an enhancing mass in the conus medullaris. The tumor
      was subtotally removed. Crush smears revealed dispersed and perivascular
      aggregates of monotonous oval or spindle tumor cells with round or oval, uniform
      nuclei; small nucleoli; and long cytoplasmic processes. Some tumor cells
      contained fine or coarse cytoplasmic brown pigments. The pigments were easier to
      discern in the crush smears than in the frozen sections. CONCLUSION: Crush
      cytology appears to be helpful, alone or in conjunction with frozen sections, in
      the intraoperative diagnosis of meningeal melanocytoma.

PMID- 14674088
TI  - Clear cell carcinoma arising in a cesarean section scar. Report of a case with
      fine needle aspiration cytology.
AB  - BACKGROUND: Clear cell carcinoma arising in a cesarean section scar is an
      extremely rare disease. To the best of our knowledge, there is no published
      report on the aspiration cytology. CASE: A 56-year-old woman presented with a
      mass in a cesarean section scar. Initially an abdominal desmoid was considered,
      but the features of fine needle aspiration (FNA) cytology suggested an
      adenocarcinoma. The resected tumor was histologically composed of clear cell
      carcinoma showing cystic, solid and papillary patterns. CONCLUSION: FNA cytology
      of masses arising in a surgical scar can be a useful tool in obtaining an
      accurate pathologic diagnosis of a malignant neoplasm.

PMID- 14674089
TI  - Oncocytic carcinoma of the parotid gland. A case report.
AB  - BACKGROUND: Oncocytic carcinoma is a rare malignant tumor of the salivary gland.
      Abundant, granular, eosinophilic cytoplasm is recognized as an oncocytic feature
      that reflects an accumulation of mitochondria. Ultrastructural study or
      immunohistochemical staining using antimitochondrial antibody can confirm the
      oncocytic nature of the tumor. However, there have been no data on whether
      immunocytochemical staining for human mitochondria aids in the confirmation of
      the oncocytic nature of oncocytic carcinoma. CASE: A 61-year-old man presented
      with a swelling in the left lower cheek. Computed tomography demonstrated a
      solid, isodense tumor in the parotid gland. An excisional biopsy of the tumor was
      performed, and an enlarged regional lymph node was removed. Imprint cytology of
      the lymph node showed cohesive cell clusters with lymphocytes. The clusters were
      composed of tumor cells that had characteristic abundant, granular cytoplasm and
      round to oval, centrally or eccentrically located nuclei with increased, fine
      chromatin and distinct nucleoli. Immunocytochemical staining revealed granular
      immunoreactivity of the cytoplasm for human mitochondria. Histology demonstrated
      tumor invasion in the normal gland and adjacent skeletal muscles. All tumor cells
      showed positive cytoplasm with antimitochondrial antibody by
      immunohistochemistry. Ultrastructural studies demonstrated packed mitochondria in
      the cytoplasm of the tumor. CONCLUSION: Immunocytochemical staining for human
      mitochondria help confirm the oncocytic nature of oncocytic carcinoma in
      cytologic specimens.

PMID- 14674090
TI  - Primary giant cell tumor of soft tissue. Report of a case with fine needle
      aspiration cytologic and histologic findings.
AB  - BACKGROUND: So-called primary giant cell tumor of soft tissue of low malignant
      potential is the rare soft tissue analogue of giant cell tumor of bone, occurring
      primarily in superficial soft tissue. To our knowledge, the cytologic findings in
      bulky giant cell tumor of deep soft tissue were described only once, and no
      further report on the subcutaneous giant cell tumor could be retrieved from the
      literature. CASE: A 58-year-old woman presented with a well-demarcated, 1.5-cm
      diameter dermal tumor. Fine needle aspiration smears contained numerous
      osteoclastlike giant cells and mononuclear cells showing bland and vesicular
      nuclei. A small fragment of branching vasculature and 1 mitosis were found. Those
      cytologic findings were enough to suggest a diagnosis of giant cell tumor of soft
      tissue, confirmed as a deep dermal giant cell on surgical resection. CONCLUSION:
      Primary giant cell tumor of soft tissue of low malignant potential should be
      considered in the differential diagnosis of bland-looking giant cell-rich
      lesions. Awareness of its existence and knowledge of its cytologic features are
      important for a correct preoperative cytologic diagnosis.

PMID- 14674091
TI  - Extramedullary plasmacytoma presenting as a primary mass in the breast. A case
      report.
AB  - BACKGROUND: Extramedullary plasmacytoma (EMP) of the breast is extremely rare,
      especially that not associated with multiple myeloma. CASE: A case of
      plasmacytoma of the breast in a 73-year-old man was diagnosed by fine needle
      aspiration cytology (FNAC). Aspiration smears revealed a dispersed population of
      plasmacytoid cells at various stages of maturation. The tumor was excised, and
      the histologic sections confirmed the cytologic diagnosis. CONCLUSION: FNAC
      diagnosis of plasmacytoma of the breast offers the opportunity to distinguish
      these neoplasms from primary mammary tumors and avoid unnecessary surgery.

PMID- 14674092
TI  - Crush cytology of Rosai-Dorfman disease of the central nervous system. A report
      of 2 cases.
AB  - BACKGROUND: Rosai-Dorfman disease (RDD) of the central nervous system (CNS) is
      rare. There is no previous report on intraoperative crush cytology of this
      disorder. CASES: A 70-year-old man presented with headache and was found to have
      2 intracranial extraaxial masses. A 62-year-old man presented with cauda equina
      syndrome secondary to a mass lesion in the sacral canal. The crush smears,
      prepared intraoperatively from a small portion of the biopsy specimen in each
      case, showed scattered lymphoid aggregates in a lighter background with a loose
      admixture of lymphocytes, plasma cells, usual histiocytes and RDD histiocytes.
      The RDD histiocytes contained single but sometimes multiple nuclei that were
      larger and more hyperchromatic than those of the usual histiocytes. Many RDD
      histiocytes had voluminous, pale pink cytoplasm. Lymphophagocytosis by RDD
      histiocytes was observed. The findings in the crush smears reflected the
      histology of the lesions. The lymphophagocytosis and nuclear details in the RDD
      histiocytes were more visible in the crush smears than in the frozen sections.
      CONCLUSION: Crush cytology appears useful, alone or in conjunction with frozen
      sections, in the intraoperative diagnosis of CNS RDD.

PMID- 14674093
TI  - Spleen metastasis from thyroid carcinoma. Report of a case with diagnosis by fine
      needle aspiration cytology.
AB  - BACKGROUND: Lymphoreticular malignancies are the most common neoplasms involving
      the spleen. Metastasis can be caused by direct invasion from surrounding tumors
      or from hematogenous spread. Spleen metastases from thyroid carcinoma are
      unusual, and only 1 case has been reported; none have been diagnosed by fine
      needle aspiration cytology (FNAC). CASE: A 75-year-old female was diagnosed 6
      months earlier with a poorly differentiated thyroid carcinoma with wide lymphatic
      and vascular invasion. Abdominal computed tomography (CT) and magnetic resonance
      imaging showed several spleen nodules. FNAC was performed under CT guidance.
      Cytologic examination showed atypical epithelial cells with thyroidal
      characteristics. CONCLUSION: This case had the cytologic findings of a poorly
      differentiated carcinoma of the thyroid metastatic to spleen. We confirmed the
      rarity of this pathology and the efficacy of splenic FNAC in the diagnosis.

PMID- 14674094
TI  - Primary Rosai-Dorfman disease of bone without lymphadenopathy diagnosed by fine
      needle aspiration cytology. A case report.
AB  - BACKGROUND: Solitary bone involvement without lymphadenopathy is a rare
      manifestation of Rosai-Dorfman disease, or sinus histiocytosis with massive
      lymphadenopathy (SHML). Only 11 cases have been reported in the literature to
      date, all diagnosed on histology. CASE: A 7-year-old girl had a radiolucent,
      lytic lesion in the shaft of the tibia clinically simulating Ewing's sarcoma.
      Fine needle aspiration cytology (FNAC) showed a microscopic picture typical--of
      SHML. There was no lymphadenopathy. CONCLUSION: Rosai-Dorfman disease sometimes
      involves bone without lymphadenopathy and can be diagnosed confidently on FNAC.
      To the best of our knowledge, this is the 12th case report of solitary bone
      involvement.

PMID- 14674095
TI  - Imprint cytology of metastatic sialoblastoma. A case report.
AB  - BACKGROUND: Sialoblastoma is a rare, aggressive and potentially malignant
      perinatal/congenital tumor that recapitulates the developing salivary gland.
      There is only 1 brief description of the cytologic findings of metastatic
      sialoblastoma and 1 poorly documented case of lung metastasis in the literature.
      CASE: A 75-month-old girl with a history of recurrent sialoblastoma initially
      diagnosed at 21 months and treated with multiple incomplete surgical excisions,
      chemotherapy and radiation presented with a solitary lung nodule. Imprint smears
      and frozen section of the mass were diagnostic of metastatic sialoblastoma.
      CONCLUSION: Cytologic features of sialoblastoma showed complete concordance with
      histology and included the presence of variably arranged, tight, solid clusters
      of atypical-appearing, basaloidlike cells in a background of dispersed epithelial
      and myoepithelial cells. The clusters contained admixed benign ductal cells and
      dense, metachromatic, magenta hyaline globular material with smooth, rounded
      outlines. The differential diagnoses include neoplasms composed of either
      basaloid cells and/or admixed hyaline matrix material and included pleomorphic
      adenoma, basal cell adenoma and adenoid cystic carcinoma. All these neoplasms
      affect patients in the first 2 years of life, whereas sialoblastoma usually
      occurs in the first 2 decades of life.

PMID- 14674096
TI  - Cytomorphologic features of a polymorphous low grade adenocarcinoma of the
      palate. A report of 2 cases with immunocytochemistry.
AB  - BACKGROUND: Polymorphous low grade adenocarcinoma (PLGA) is a histologically low
      grade tumor of minor salivary gland origin. It is important to differentiate PLGA
      from other salivary gland tumors with myoepithelial differentiation, such as
      pleomorphic adenoma, adenoid cystic carcinoma and epithelial myoepithelial
      carcinoma. Here we report 2 cases of PLGA originating in the palate and describe
      the cytomorphologic and immunocytochemical features. CASES: The patients were a
      55-year-old woman and a 63-year-old man. Both presented with a mass in the
      palate. Clinically the mass appeared malignant, and resection was performed.
      Cytologically the tumor cells were composed of sheet clusters, pseudopapillary
      epithelial clusters, naked cells and stromal components. Immunocytochemically the
      tumor cells showed strong expression of carcinoembryonic antigen (CEA) and
      vimentin. CONCLUSION: PLGA may be difficult to distinguish from other salivary
      gland tumors with myoepithelial differentiation. However, the cytopathologist
      should be aware of the distinctive cytomorphologic features of PLGA,
      demonstrating immunopositivity to CEA and vimentin.

PMID- 14674097
TI  - Fine needle aspiration biopsy of intraparotid schwannoma. A case report.
AB  - BACKGROUND: Intraparotid schwannoma of the salivary gland is a rare entity.
      Review of the literature revealed one previous report describing its cytologic
      features. CASE: A 22-year-old man had a slowly growing, painless mass in the left
      parotid gland. Fine needle aspiration biopsy, performed prior to surgical
      excision, showed several tissue fragments consisting of uniform, spindle-shaped
      neoplastic cells with cigar-shaped nuclei and scant, ill-defined cytoplasm. Some
      of the neoplastic cells were clustered in typical arrangements of Verocay bodies.
      In addition, lymphocytes and foamy histiocytes were found. A diagnosis of
      schwannoma was made. Pathologic evaluation of the resected parotid mass supported
      the diagnosis. CONCLUSION: The diagnosis of intraparotid schwannoma can be made
      by examining cytologic material containing the characteristic Verocay bodies. The
      correct cytologic diagnosis of this entity helps to rule out morphologically
      similar primary salivary gland neoplasms and thereby permits the appropriate
      surgical procedure to ensue.

PMID- 14674098
TI  - Alternative fixation techniques for conventional Pap Smears.

PMID- 14674099
TI  - Difficulty of cytodiagnostic approaches to pulmonary metastases from a case of
      low grade endometrial stromal sarcoma.

PMID- 14674100
TI  - Papillary thyroid carcinoma, diffuse sclerosing variant, with abundant psammoma
      bodies.

PMID- 14674101
TI  - Squash cytology of Rosai-Dorfman disease in the sellar region.

PMID- 14674102
TI  - BK viral infection in kidney transplantation: importance of "decoy" cells.

PMID- 14674103
TI  - [Coexistence of VIN and vulvar invasive cancer with intraepithelial neoplasia and
      invasive carcinoma of the cervix and/or vagina, and HPV infection of the low
      female genital tract].
AB  - INTRODUCTION: A frequency of VIN and vulvar carcinoma is continuously increasing,
      especially in young women in whom the changes are often multifocal. AIMS:
      Evaluation of VIN and vulvar carcinoma coexistence with intraepithelial as well
      as invasive changes within vagina and uterine cervix and estimation of the
      frequency of HPV infection accompanying these changes. MATERIAL AND METHODS:
      Study group was consisted of 389 women aged 22-92 y. Cytologic, colposcopic
      examinations of the entire low genital tract and diagnosis of HPV infection with
      use of DNA HPV hybridization technique were performed in all cases. There were
      148 (38.0%) cases of vulvar changes in women below 45 yrs of life, and 241
      (62.0%) cases in older patients. HPV infection was diagnosed in 91 (61.5%) young
      women and in 41 (17.0%) women over 45 yrs. Intraepithelial neoplasia or invasive
      cancer of vagina and/or uterine cervix were diagnosed in 16 (10.8%) cases of
      young patients, and HPV infection of high oncological potential was diagnosed in
      13 (81.3%) of these patients. CONCLUSIONS: There is a high percent of coexistence
      of intraepithelial as well as invasive changes of the vulva, vagina and uterine
      cervix which mostly coexist with HPV infection of high oncological potential.
      These data suggest an important role of HPV infection in low female genital tract
      carcinogenesis and obliges to a precise examination of the entire low female
      genital tract, especially in young women.

PMID- 14674104
TI  - [Photodynamic diagnosis of vulvar precancerous conditions and invasive cancers
      using 5-aminolevulinic acid].
AB  - BACKGROUND: Photodynamic therapy (PDT), in particular Photodynamic diagnosis
      (PDD) is a modern, non-invasive technique using photosensitizer like 5
      aminolevulinic acid (5-ALA) in detection of the vulvar diseases. Photodynamic
      therapy gives the possibilities to differentiate inflammatory diseases from
      precancerous lesions and invasive vulvar cancer. OBJECTIVE: To assess accuracy of
      the PDD in detection, localisation and differentiation of precancerous diseases
      and invasive cancer of the vulva. MATERIAL AND METHODS: This study included 107
      patients with vulvar disorders, 30 patients with VIN I, 31 patients with VIN II,
      and 46 patients with VIN III and vulvar carcinoma. All women underwent a standard
      gynaecologic examination. 5-ALA was topically applied to the vulva. After 180-360
      minutes the vulvar skin was illuminated by a short--are xenon lamp at 380-440 nm
      and an output of 200 mW (D-Light; Karl storz). A filter to select the emitted
      wavelength range 630-670 nm was used in order to achieve differentiation's of the
      fluorescence--positive and negative areas. After the PDD, biopsies were taken
      from patients with multifocal VIN lesions. Macroscopic appearance, fluorescence
      pattern in scale of three degrees (zero, +, ++) and histology of the lesions were
      compared. RESULTS: The sensitivity, specificity, positive and negative predictive
      value for the detection of VIN I were 85.7%, 81.2%, 80.0%, 86.6% respectively,
      for VIN II there were 93.3%, 93.7%, 93.3% and 93.7%, and for VIN III and invasive
      vulvar cancer there were 96.3%, 94.7%, 96.3% and 94.7% respectively. The
      sensitivity, specificity, positive and negative predictive value for the
      detection of all VIN and invasive vulvar cancer common were 92.9%, 90.2%, 91.2%,
      92.0 respectively. CONCLUSION: The Photodynamic therapy becomes a valuable, non
      invasive diagnostic tool that lowers the amount of false negative diagnosis in
      cases of VIN and vulvar cancer.

PMID- 14674105
TI  - [Sentinel node biopsy in breast cancer and primary tumor dimension].
AB  - INTRODUCTION: Sentinel lymph node (SLN) biopsy, primary used as an alternative to
      elective lymph node dissection in melanoma, is being applied successfully in
      management of patients with breast cancer. The aim of this method in breast
      cancer is to determine the presence of axillary node involvement while clinically
      normal axilla. The validity of the sentinel node concept in breast cancer is
      demonstrated in various studies. The results of identification rates,
      sensitivity, overall accuracy and false negative rate are so encouraging in most
      publications, as to implement this concept to every-day surgical practice. There
      is lack, however, of many fundamental answers pertaining relationship between
      tumor-size and the results of SLN Biopsy or related surgical standards. MATERIALS
      AND METHODS: 36 females at the age 33-66, with breast cancer underwent primary
      surgical treatment with SLN Biopsy in Department of Gynaecology and Oncology
      Jagiellonian University between 2001-2002. The study inclusion criteria were
      tumour size-T1, T2. The day before surgery the static scanning was performed
      after injection of Tc radiolabelled nannocolloid. SLN(s) were identified
      intraoperatively using a handheld gamma detection probe (Navigator GPS) and
      intraoperative lymphatic mapping with blue dye (Patent Blau V). After
      localization and excision of SLN(s), axillary's lymph node dissection (ALND) was
      performed. RESULTS: In 34 patients SLN Biopsy revealed accumulation of the tracer
      in axilla, which was classified as SLN. Detection rate was 94.4% (34/36). Overall
      sensitivity of the procedure was 81%, whereas negative predictive value 92%.
      False negative rate was 2.2%. Detection rate for T1 tumors was 100% (15/15
      cases), and for T2 tumors was 90.4% (19/21 cases). Sensitivity for tumor
      classified as T1 was 100% (3/3 cases), whereas for tumor T2 was 75% (6/8 cases).
      CONCLUSION: SLN Biopsy seems to be very interesting alternative to ALND in
      patients with small tumor's dimension.

PMID- 14674106
TI  - [Risk of lymph node metastases in patients with ovarian cancer].
AB  - AIM: The aim of this study was the assessment of incidence of the lymph node
      spread in patients with ovarian cancer. Additionally, some of clinical and
      histopathology factors, as well as patients age were analyzed in relation with
      lymph nodes metastases. MATERIAL AND METHOD: Based on 112 operations performed in
      patients with ovarian cancer FIGO stage I-IV, analysis of pelvic and paraaortic
      lymph node metastasis was carried out. In this group only in 70 patients
      paraaortic lymph nodes were removed. The rest of patients underwent pelvic
      lymphadenectomy only because of poor general condition or very intensive
      cytoreductive surgery. Statistical analysis was provided using unvaried
      regression test and Pearson test. RESULTS: In early stages of ovarian cancer (I
      and II) the percent of patients with involved lymph nodes was 17.4 and in
      advanced stages 37.9. Strong correlation between involvement of pelvic and
      paraaortic lymph nodes was seen. The most frequent localization of lymph node
      metastases was the site around intercrossing of left renal vein and aorta. It
      should be stressed that in 8 cases isolated paraaortic metastases were seen. Risk
      factors of lymph node metastases were clinical stage, tumor grade and age of
      patients. Clear cell carcinoma and mixed carcinoma had also prognostic
      significance. CONCLUSION: This analysis proved that incidence of lymph node
      metastases was high even in early stage, and therefore lymphadenectomy should be
      an integral part of standard surgical procedures in patients with ovarian cancer.

PMID- 14674107
TI  - [Assessment of the influence of chemotherapy on the nucleolar organizer regions
      (AgNORs) count in serous ovarian cancer cells].
AB  - OBJECTIVE: When planning treatment of ovarian cancer, the prognostic factors
      should be considered. One of them is the amount of nucleolar organizer regions
      (AgNORs) in cancer cells, which reflects proliferative activity of the tumor.
      DESIGN: To estimate the influence of chemotherapy on the AgNORs count in serous
      ovarian cancer cells. MATERIAL AND METHODS: 26 women who underwent surgical
      procedure and then chemotherapy between 1998-2002 due to serous ovarian cancer
      were included into the study. During the initial surgery the cancer stage I was
      detected in 1 case, stage II in 2 cases, stage III in 12 cases, and stage IV in
      11 cases. In all cases during second-look laparotomy, which was performed after 6
      courses of chemotherapy (paclitaxel, cisplatinum), the persistent disease was
      found. In 17 out of 26 cases it was disseminated neoplasmatic disease. In all
      cases the specimens were prepared according to one-step AgNORs method described
      by Howell and Ploton. In cancer cells the mean number of AgNORs per nucleus
      (mAgNOR) and the mean percentage of nuclei with five or more AgNORs per nucleus
      (pAgNOR) were counted. RESULTS: The mAgNOR and pAgNOR mean number before
      chemotherapy were respectively: 4, 22 +/- 0.94 and 35.62 +/- 19.90. After
      treatment the mAgNOR and pAgNOR were significantly lower, and the data were
      respectively: 3.67 +/- 0.91 and 24.15 +/- 19.53. In 4 cases (15.4%) the mAgNOR
      increased, in 7 cases (26.9%) the change was not significant, and in 15 cases
      (57.7%) the mAgNOR decreased. In 6 cases (23.1%) the pAgNOR increased, in 5 cases
      (19.2%) the change was not significant, and in 15 cases (57.7%) the pAgNOR
      decreased. We did not found any correlation between the tendency to change the
      number of AgNORs and staging, the amount of persistent neoplasmatic tissue, the
      range of primary surgery, as well as grading. CONCLUSIONS: The number of AgNORs
      per nucleus in most cases of ovarian cancer after chemotherapy was lower. The
      tendency to change the number of AgNORs was not connected with staging as well as
      grading.

PMID- 14674108
TI  - [Value of fine needle aspiration biopsy in cervical cancer].
AB  - Correct staging qualification, especially evaluation of parametrium is very
      useful in choosing of adequate method of treatment, and thereby in patients'
      survival. OBJECTIVE: The aim of study was estimation of the value of fine needle
      aspiration biopsy in transvaginal ultrasonography assistant in preoperative
      assessment of parametria in cervical cancer. We compared parametrial infiltration
      before treatment and to verified and confirmed staging in cervical cancer
      postoperatively by histopathology. MATERIAL AND METHOD: 64 women with cervical
      cancer in stage Ib, were included in the study. Assessment of parametrial
      invasion before treatment was performed by fine needle aspiration biopsy in
      endovaginal ultrasound assistants. The sonographic evaluation of parametria was
      performed by Siemens Sonoline Versa Pro with transvaginal 7 MHz mechanical
      transducer with the biopsy guide 14 cm long. All of patients with cervical cancer
      in stage Ib were operated on Wertheim-Meigs hysterectomy. The preoperative
      findings were compared with data obtained by histopathology findings. There were
      evaluated sensitivity, specificity and diagnostic accuracy of this method.
      RESULTS: Accuracy of fine needle aspiration biopsy of parametrial involvement was
      89%, sensitivity-70%, specificity-92.6%, PPV-63.6%, NPV-94.3%. CONCLUSIONS:
      Transvaginal ultrasonography is superior to routine clinical examination in the
      assessment of parametria. Sensitivity of fine needle biopsy with ultrasound
      assistance is higher then of gynecological examination and ultrasound alone.
      Correct preoperative diagnosis may improve staging, treatment and indirectly,
      survival patients with cervical cancer.

PMID- 14674109
TI  - [Granulosa cell tumor in different periods of women's life].
AB  - Ovarian granulosa cell tumor is uncommon malignancies. By virtue of
      histopathological examination we distinguish two subtype of GCT: adult type
      granulosa cell tumor typically in older women and juvenile granulosa cell tumor
      recognized primarily in children and young adults. GCTs behave unpredictably.
      Depending on histological type patients suffer recurrences in different time
      after treatment, even many years from diagnosis. OBJECTIVES: The aim of our study
      is clinical analysis of patients with AGCT and JGCT, especially the problem of
      choice of treatment, time to occurring recurrences and new possibility in long
      term follow up. MATERIAL AND METHODS: We analyzed 22 patients treated in
      Department of Gynecological Surgery and Oncology of Adults and Adolescent
      Pomeranian Academy of Medicine and then observed in our outpatient clinic.
      RESULTS: Among analyzed 22 patients 18 had adult type of granulosa cell tumor,
      mean age of these women was 47 years (32-72). Juvenile type of granulosa cell
      tumor were recognized in 4 patients and they were from 4 to 7 years old. All
      young girls were underwent sparing surgery, one of them was treated with
      radiotherapy. In histopathological examination of 4 years old girl atypia and a
      lot of mitosis was observed and she was treated with chemotherapy. Unfortunately
      after 18 months from diagnosis she died due to very dynamic recurrence. Remained
      3 girls live without evidence of disease and the longest time of follow up is 36
      years. 16 women with AGCT were underwent total abdominal hysterectomy, bilateral
      salpingo-oophorectomy and omentectomy, 2 were performed conservative surgery
      because they wish to preserve their fertility. 16 patients were treated with
      radiotherapy as an adjuvant treatment, two additionally with GnRH analogues.
      Recurrences in patients with AGCT were recognized in 5 cases. Mean time to
      recurrence from diagnosis were 11.7 years. In two patients it happened after 21
      and 22 years. Despite of aggressive chemotherapy four of these patients died
      during one year. Remained 13 women with adult granulosa cell tumours live without
      evidence of disease and the longest time of observation is 9 years. In
      histopathological examination of all patients who died were describe cellular
      atypia and high mitotic rates. During long time follow up our patients were
      performed second-look laparoscopies, tested of estradiol levels and 5 of them
      also inhibin B levels which always correlated with actual condition. CONCLUSION:
      Granulosa cell tumor is ovarian neoplasm of different behaviour. Patients with
      this diagnosis should be monitoring for many years. Inhibin is valuable
      examination in long term follow up.

PMID- 14674110
TI  - [Color Doppler blood flow measurements and microvessel density assessment in
      ovarian tumors].
AB  - OBJECTIVE: The aim of our study was to compare ultrasound vascular blood flow
      indices with the expression of CD-34 in women with benign and malignant adnexal
      tumors. MATERIALS AND METHODS: Transvaginal color and pulsed Doppler sonography
      was performed before surgical procedure in 105 women with adnexal tumors. Blood
      flow indices: pulsatility index (PI) and resistive index (RI) in blood vessels
      with the highest flow velocity were measured within each tumor.
      Immunohistochemical analysis of microvessel density (MVD) was performed on
      representative highly vascular tumor specimens fixed in 10% formalin and paraffin
      embedded. The primary monoclonal mouse anti-human CD-34 antibody (1:25, DAKO,
      Denmark) was used. Statistical calculations included group comparison with
      Kruskal-Wallis ANOVA on ranks and correlation analysis (Statistica for Windows
      6.0, Statsoft Poland). RESULTS: Mean age of the studied women was 55.6 +/- 11.5
      yrs. Of 104 tumors, 35 (33.6%) were benign and 69 (66.4%) were malignant. The
      latter included 14 FIGO stage I cases. Low resistance or pulsatility indices (RI
      < 0.5 or PI < 0.8) were found in 58 of 69 (84%) malignant masses and in 21 of 35
      (60%) benign tumors. Substantial overlap in measured indices was found between
      both studied groups. Median number of microvessels per high power field in the
      benign and malignant tumors were 37 (range: 14-156) and 68 (range: 25-177),
      respectively. These differences were statistically significant (p = 0.007, Mann
      Whitney U test). Also, a significant correlation was found between MVD and low
      resistance to blood flow as measured by the PI or RI (r = 0.43, p < 0.05).
      However, no statistically significant differences in MVD were found between FIGO
      stage I and other stages of ovarian cancer. CONCLUSION: Low resistance to blood
      flow as measured by the resistive or pulsatlity indices used in color Doppler
      sonography may by positively correlated with the microvessel density in the
      malignant ovarian tumors.

PMID- 14674111
TI  - [Cancer antigen CA 125 in ovarian cancer].
AB  - AIM: To estimate the diagnostic and prognostic value, pathological and clinical
      correlation of cancer antigen 125 (CA125) in ovarian cancer (OC). Retrospective
      analysis was done of 350 patients who were operated for OC in years 1990-2001 in
      Gynecology Clinic MU of Gdansk. We analyzed those before primary operation (PO)
      and second look laparotomy (SLL). Chi 2 and t-Student tests were used. RESULTS:
      Before PO 18% OC patients had CA125 less than 35 and 43.8% more than 600 U/ml,
      for benign tumors it was 59.9 and 1.1 respectively (p < 0.001). 56.2% with
      complete remission and 43.8% with progress disease in SLL had normal values of
      antigen before the operation. There were 32 patients who had CA125 > 600 before
      SLL and all of those had progress disease. The positive and negative predictive
      value of CA125 before SLL were 0.94 and 0.56 respectively. Cytoreduction with no
      macroscopic disease was achieved in 45% of patients with CA125 < 600 U/ml before
      PO, and it was 19.2% for those with antigen > 600 (p = 0.001). We looked for
      differences of CA125 levels depending on clinical and pathological data.
      According to our results only histology (p = 0.02) and clinical stage (p = 0.02)
      influenced CA 125 levels. CONCLUSIONS: There is a good correlation between
      elevated levels of CA125 and state of the disease in SLL, and we consider SLL as
      obligatory to perform as there is a low negative predictive value of CA125. The
      CA125 before primary operation has prognostic significance to possibility of
      optimal cytoreduction.

PMID- 14674112
TI  - [Influence of physiologic 17 beta-estradiol concentrations on gene E6 expression
      in HVP type 18 in vitro].
AB  - Many recent studies indicate that long term use of contraceptives is a strong
      risk factor in the development of cervical cancer. Steroid hormones, in
      persistent papilloma virus infection act on various levels, one of them is
      enhancing transforming activity of the virus. The aim of the study was to
      estimate if physiological concentrations of 17 beta-estradiol could influence
      expression of viral transforming genes. HeLa cell lines were incubated with three
      different physiological concentrations and and on the third day of incubation the
      level of E6 gene expression was determined. Results show no differences in
      expression between the control culter, and cultures incubated with physiological
      concentrations. It indicates that normal levels of 17 beta-estradiol don't play
      role in transforming process but it also shows need to analyse higher levels of
      hormones by quantitative analyses in prospective studies.

PMID- 14674113
TI  - [Malignant tumors of the female genital track in the elderly].
AB  - OBJECTIVE: In senium the increase in the incidence of most malignant neoplasms,
      as well as gynecological cancers is found. In this period of life the vast number
      of women do not apply for the preventive and follow-up examinations, which
      increases the number of malignant diseases diagnosed at advanced clinical stages.
      The coexisting another diseases often limits the possibility of the operative
      treatment in those cases. DESIGN: To assess the profile of malignant tumors of
      the genital tract and their treatment in women above 70 year old. MATERIAL AND
      METHODS: 61 women aged from 71 yrs. to 88 yrs. treated operatively between 1997
      2001 due to gynecological cancers were included into the study. The structure and
      detectability of the neoplasms, as well as the type of performed surgical
      procedures were analysed. RESULTS: 30 endometrial cancers (49.2%), 16 ovarian
      cancers (26.2%), 14 vulvar cancers (22.9%) and 1 cervical cancer were diagnosed
      and surgically treated. The endometrial cancer stage I was detected in 18 cases,
      stage II in 4 cases and stage III in 8 cases. In each case the radical operation
      was done (total hysterectomy, lymphadenectomy and appendectomy). The ovarian
      cancer stage I was detected in 3 cases, stage II in 2 cases, stage III in 5
      cases, and stage IV in 6 cases. Only in 5 cases out of this group the radical
      surgery was performed (total hysterectomy, omentectomy and appendectomy). The
      vulvar cancer stage I was detected in 2 cases, stage II in 11 cases, and FIGO
      stage III in 4 cases. In each of these women the vulva and bilateral inguinal
      lymph nodes were resected, and in 2 cases additionally at the same time the Miles
      operation was performed. The cervical cancer clinical stage I was detected, and
      the Wertheim operation was performed. CONCLUSIONS: The most often diagnosed
      malignant neoplasm in women above 70 yrs. was the endometrial cancer. The worst
      first-time diagnosis structure was observed in the ovarian cancer, what
      significantly decreased the ability of surgical treatment in this group.

PMID- 14674114
TI  - [Assessment of the midwives preparation to take care of patients with cervical
      cancer].
AB  - INTRODUCTION: The success of the cervical cancer treatment depends not the only
      on the early diagnosis, but also on the immediate initiation of the appropriate
      treatment and proper nursing care, which should be adequate with the present
      knowledge. OBJECTIVE: The objective of the research was the assessment of the
      theoretical preparation of nurses taking care of patients with cervical cancer.
      MATERIALS AND METHOD: 50 nurses, working in the departments of gynecological
      diseases, have been interviewed. All the nurses graduated from College of
      Nursing, 3 of them additionally studied in the Pedagogical Graduate School. 60%
      of the nurses had 10-20 years of professional experience. We used special
      questionnaire made of 3 parts: describing the objective of the research/test,
      characteristics of the patient, specific questions. There were 18 questions: 5
      closed, 1-open, 12-semiopen. They were checking the knowledge about the
      diagnostics, preparation of the patient to the operation using Wertheim-Meigs
      Valle method, postoperative care until the discharge from the hospital and then
      oncological care. RESULTS: Almost all of them (88%-92%) have known the sequence
      of the diagnosis and treatment of the cervical cancer. 90% of them have been
      knowledgeable what kind of diagnostic and nursing procedures were required before
      the surgery using Wertheim-Meigs-Valle method. Almost all of the tested nurses
      (96%-100%) have known the procedure of postoperative care. They had a practical
      knowledge how to assess the patient condition and components of care that the
      patients require during the first few days after the surgery. According to the
      tested nurses, 90% of the patients operated because of cervical cancer, should
      follow up in oncological centers. CONCLUSION: 1. The nurses' preparation to take
      care of patients with cervical cancer is sufficient and it affects the
      effectiveness of the treatment. 2. The nurses have knowledge about pre- and
      postoperative procedures that the patients require, as well as assessment of
      general condition and patients' care, which are so important in the first few
      days after the surgery.

PMID- 14674115
TI  - [Microcytomorphometric video-image detection of nuclear chromatin in ovarian
      cancer].
AB  - Technology of detection of tissue preparates precisious evaluates contents of
      nuclear chromatine, largeness and shape of cellular nucleus, indicators of
      mitosis, DNA index, ploidy, phase-S fraction and other parameters. Methods of
      detection of picture are: microcytomorphometry video-image (MCMM-VI), flow,
      double flow and activated by fluorescence. Diagnostic methods of malignant
      neoplasm of ovary are still nonspecific and not precise, that is a reason of
      unsatisfied results of treatment. OBJECTIVE: Evaluation of microcytomorphometric
      measurements of nuclear chromatine histopathologic tissue preparates (HP) of
      ovarian cancer and comparison to normal ovarian tissue. MATERIAL AND METHODS:
      Estimated 10 paraffin embedded tissue preparates of serous ovarian cancer, 4
      preparates mucinous cancer and 2 cases of tumor Kruckenberg patients operated in
      Clinic of Perinatology and Gynaecology Silesian Medical Academy in Zabrze in
      period 2001-2002, MCMM-VI estimation based on computer aided analysis system:
      microscope Axioscop 20, camera tv JVCTK-C 1380, CarlZeiss KS Vision 400 rel.3.0
      software. Following MCMM-VI parameters assessed: count of pathologic nucleus,
      diameter of nucleus, area, min/max diameter ratio, equivalent circle diameter
      (Dcircle), mean of brightness (mean D), integrated optical density (IOD = area x
      mean D), DNA index and 2.5 c exceeding rate percentage (2.5 c ER%). MCMM-VI
      performed on the 160 areas of 16 preparates of cancer and 100 areas of normal
      ovarian tissue. Statistical analysis was performed by used t-Student test.
      RESULTS: We obtained stastistically significant higher values parameters of
      nuclear chromatine, DI, 2.5 c ER of mucinous cancer and tumor Kruckenberg
      comparison to serous cancer. MCMM-VI parameters of chromatine malignant ovarian
      neoplasm were statistically significantly higher than normal ovarian tissue.
      CONCLUSION: Cytometric and karyometric parametres of nuclear chromatine estimated
      MCMM-VI are useful in the diagnostics and prognosis of ovarian cancer.

PMID- 14674116
TI  - [Role of immunomodulatory treatment with Iscador QuS and Intron A of women with
      CIN1 with concurrent HPV infection].
AB  - OBJECTIVE: The paper presents the role of immunomodulatory treatment with Iscador
      QuS and Intron A of women with CIN1 and CIN2 with concurrent HPV infection.
      MATERIAL AND METHODS: Clinical material consisted of 96 women aged 18-52 years of
      life. The women were divided into three groups. Group A (35 women) treated with
      Iscador QuS administered s.c. twice a week for 3 months, group B (30 women)
      treated with Intron A, administered twice a week in the cervical injections for 3
      months and control group K (31 women) without treatment followed up with cytology
      and colposcopy. RESULTS: In the group A (Iscador QuS) CIN remission was observed
      in slightly higher percentage (non significant) comparing to the control group.
      In the group B (Intron A) remission CIN was observed in 24 (80%) cases which was
      statistically significant comparing to the control and A groups. There were no
      progression of CIN in the group B and the stationery process was observed
      statistically more frequent comparing to the control and A groups. There was
      observed statistically higher percentage of cases without HPV infection in all
      groups during the experiment. The remission concerned both high and low oncogenic
      potency viruses. In the highest percentage CIN with concurrent HPV infection
      remission was observed in the B (Intron A) group. CONCLUSIONS: 1/Iscador QuS and
      specially Intron A increases the CIN1 and CIN2 remission rate. 2/These two agents
      may also affect the HPV remission.

PMID- 14674117
TI  - [Quantitative competitive RT-PCR method in analysis of aromatase expression in
      breast cancer].
AB  - 17 beta estradiol plays an important role in breast cancer development, growth.
      Aromatase, a cytochrome P-450 enzyme that catalyzes the conversion of androgens
      to estrogens, is responsible for estrogen biosynthesis in the post-menopausal
      women. Aromatase transcripts have been detected in the breast cancer cells, where
      the 30-100 fold higher concentration of estrogen in comparison with the plasma
      level were found. Suppression of local estrogen biosynthesis can be achieved by
      inhibition of aromatase expression in breast cancer. In order to determine
      aromatase mRNA level in breast cancer tissue we propose the quantitative
      competitive RT-PCR method using internal standard of aromatase. As a housekeeping
      gene we have used GAPDH. The determination of aromatase expression in breast
      cancer might aid in selecting patients for aromatase inhibitor therapy as a first
      line hormonal treatment.

PMID- 14674118
TI  - [Expression P53 protein and chromosome aberrations in benign tumors and ovarian
      carcinoma].
AB  - OBJECTIVES: The epithelial ovarian tumors arise from the single layer of
      epithelial cells that line the ovarian surface or from underlying inclusion
      cysts. One from many theories of oncogenesis has been proposed that benign,
      borderline and invasive tumors represent sequential stages in the growth of an
      ovarian cancer, and p53 tumor suppressor gene mutation is the most common
      molecular genetic alteration. Because locus of p53 gene is located on 17
      chromosome we performed the cytogenic analysis of tumor tissues. DESIGN: Analysis
      of mutated p53 protein expression and chromosomal aberrations in tissues of
      benign tumors and epithelial ovarian carcinomas. MATERIAL AND METHODS: Tissue
      samples from 19 women with benign and 17 women with invasive epithelial ovarian
      cancers were obtained for the study at the time of surgical procedures. From
      among benign tumors 12 were serous cystadenomas, 5 were endometrial cysts and 2
      adult teratomas. All cases of invasive epithelial ovarian carcinomas were
      histologically recognized as serous adenocarcinomas, and were staged on I (9
      cases), II (5 cases) and III (3 cases), according to the FIGO guidelines for
      ovarian cancers. Frozen tissue samples were stained immunohistochemically for
      mutated p53 protein using commercial monoclonal antibodies and standard detecting
      system. The fresh tumor samples were prepared for cytogenic analysis according to
      standard protocol. RESULTS: Among the all benign ovarian tumors overexpression of
      mutated form of p53 protein was not seen in any cases, but was noted in 6 cases
      in I stage and in all cases in II and III stages of advanced ovarian cancers. In
      1 case of benign ovarian tumor deletion of X chromosome was observed. Most common
      numerical changes were observed in ovarian carcinomas e.g. loss of 8, 13, 17, and
      22 chromosomes. Other chromosomes were involved at least once in structural
      rearrangements and several breakpoint cluster regions were identified: 19p13,
      11p13-15, 1q21-23, 1p36, 19q13, and 6q21-23. CONCLUSIONS: The mutated form of p53
      protein is often expressed in ovarian epithelial carcinoma tissues. This protein
      are unable to function effectively to inhibit proliferation and accumulate in the
      cells because is resistant to degradation. In tissues of ovarian carcinomas many
      chromosomal nondisjunctions (monosomics) and multiple structural rearrangements
      were observed, what means of genetically nonstable cell lines of neoplasms and
      probably it heterogenous origin.

PMID- 14674119
TI  - [Neoplasms and medical thermodynamics].
AB  - Oncology--just as every field of medicine that deals with etiology, diagnostics,
      pathomechanism and treatment of diseases--is only a part of the general human
      knowledge, whose all significant achievements must be used to protect human
      health. This pursuit has as its object not only the benefits form practical
      discoveries (L. Pasteur, W.C. Roentgen, P. Curie and M. Sklodowska-Curie, V.
      Schally etc.), but also theoretical generalizations (A. Einstein, W.K. Heisenberg
      and I. Prigogine). Unfortunately it is the lack and/or slow adaptation of that
      information, that is responsible for the still unsatisfactory progress in
      clinical oncology. Responsibility rests not only with oncologists, but primarily
      with editors of medical journals and textbooks, who have a moral duty to follow
      the entire general knowledge, especially in the field of the basic research. On
      the basis of an analysis of the contents of the Polish oncology textbooks and
      materials from the specialist conferences in gynaecologic oncology, they were
      found to: 1. Omit the current, particularly domestic literature, 2. Contain
      mostly works, whose conclusions are textbook information, 3. Rarely include
      studies in the area of medical thermodynamics, 4. Attempt to explain the effects
      of the modern technologies, e.g. fotodynamics or nanotechnology using theoretical
      generalizations which are inadequate for them, and 5. Disregard the rule primum
      non nocere not only in prevention but even in the treatment of neoplasms.
      Neoplastic disease has many conditionings and types because of the unique
      identity of the neoplasms which cause it and which are caused by universal and
      natural phenomena of the self-organizing dissipative structures. It requires not
      only early diagnosing but also causative treatment already in the precancerous
      states, which are better detected by modern methods based on the quantum
      thermodynamics (lasers, fotodynamics, nuclear magnetic resonance, genetic
      nanotechnology etc.).

PMID- 14674120
TI  - [Comparative studies of K1-67 expression between the primary tumor and breast
      cancer metastases to regional lymph nodes].
AB  - Breast cancer is often relatively slow growing, but at diagnosis about 40% of
      patients have regional spread to at least one axillary node. It has been shown
      that unrelated clones are in primary breast carcinomas. There is possibility that
      only a small subpopulation of the cells of the primary tumour (PT) metastasis. It
      has been shown that Ki-67 protein is a useful marker in histopathology, which is
      present during all active phases of the cell cycle and making possibility to
      assess growth fraction of tumour cells. The purpose of the study was to evaluate
      the expression of Ki-67 and comparison between the PTs and MRLNs as well as to
      estimate the relationships between Ki-67 and the chosen anatomoclinical features
      of the breast cancer. Immunohistochemical analyses for Ki-67 were performed on
      the PTs (69 cases without primary chemotherapy) and MRLNs (33 cases) of breast
      cancer. Increased expression of Ki-67 in PTs significantly correlated with pT2
      stage of tumours (p < 0.05) and grade G3 (p < 0.04), but there was not
      relationship with lymph node status. Expression of Ki-67 positively correlated
      between PTs and MRLNs (p < 0.001). Comparison between PTs and matching MRLNs
      revealed that 23 (69.7%) cases showed a convergence between PTs and matching
      MRLNs with regard to negative or positive staining. We would like to emphasize
      the importance of studies concerning the proteins involved in proliferation in
      MRLNs, because knowledge about heterogeneity between PTs and MRLNs could shed
      light on tumour biology and may lead to development of more effective anti-cancer
      therapies.

PMID- 14674121
TI  - [Significantly increased interleukin-1A and interleukin-1 soluble type II
      receptor levels in women with ovarian cancer].
AB  - OBJECTIVES: Recent studies indicate that interleukin-1 alpha (IL-1 alpha) is an
      autocrine growth factor for some ovarian cancer cells and suggest that IL-1 alpha
      plays an important role in the progression of this disease. However, soluble IL-1
      receptors as IL-1 sRII, can modulate the effects of IL-1 alpha by acting as IL-1
      alpha antagonists. The aim of our study was to compare serum IL-1 alpha and IL-1
      sRII levels in patients with benign and malignant gynaecological tumours and in
      control. MATERIALS AND METHODS: Pretreatment serum samples were obtained from 72
      women with gynaecological tumors. This study included 37 patients with
      gynaecological cancers (21 with cervical cancer, 16 with ovarian cancer), and 35
      women with benign gynaecological disorders (20 with ovarian tumour, 15 with
      uterine myoma). As a control group, sera were obtained from 20 healthy female
      volunteers. The levels of IL-1 alpha and IL-1 sRII were measured by ELISA (R&D
      Systems, Inc, Minneapolis, USA). RESULTS: Serum IL-1 alpha and IL-1 sRII levels
      in women with ovarian cancers were significantly higher than those in cervical
      cancer, and in patients with benign disorders, and in healthy control (p <
      0.0001). CONCLUSIONS: Our results suggests that IL-1 alpha has a strong
      association with ovarian cancer.

PMID- 14674122
TI  - The impact of progesterone on simultaneous, local secretion of IGFBP-3 and IGF-I
      [IGFBP-3/IGF-I index] by human malignant and non-malignant breast explants
      depends on tissue steroid receptor phenotype.
AB  - OBJECTIVES: Insulin-like growth factor-I (IGF-I) is regarded as one of mammary
      tissue proliferative factors. Insulin-like growth factor binding protein-3 (IGFBP
      3) limits the IGF-I binding potential to its receptor. That limits the IGF-I
      bioavailability. Recently experimental studies indicated that insulin-like growth
      factor binding proteins (IGFBPs) might have their own biological actions beyond
      their ability to regulate insulin-like growth factors (IGFs). Our earlier results
      showed the progesterone-induced rise in hGH and IGF secretion by human breast
      cancer explants. AIM: To determine the ability of progesterone to stimulate
      simultaneous local IGF-I and IGFBP-3 secretion by non-malignant and malignant
      mammary tissue collected from different receptor phenotype tumours. MATERIAL AND
      METHODS: Explants from the tumour and surrounding normal non-malignant tissue
      were obtained during surging. Breast cancer explants were defined as: ER+ PR+; ER
      PR-; ER+ PR-; and ER-PR+. Part of the explants was fixed in 10% buffered formalin
      for steroid receptor determination by immunohistochemistry. Other parts were cut
      into small pieces, weight and cultured in Parker medium (M199) supplemented with
      5% of calf serum at 37 degrees C in an atmosphere containing 5% CO2 for 48 hours
      in control medium or with the addition of progesterone (10-7 M). Later media were
      collected for IGF-I and IGFBP-3 concentration analysis. RESULTS: Progesterone
      increased (p < 0.01) IGFBP-3/IGF-I index in ER(-)PR(-) non-malignant tissue and
      decreased the IGFBP-3/IGF-I index in ER(-)PR(+), ER(+)PR(-) non-malignant
      explants. That increased the IGF-I bioavailability. Breast malignant explants
      showed the progesterone induced IGFBP-3/IGF-I index decrease. The decrease was
      most evident (p < 0.01) in malignant explants expressing progesterone receptor.
      CONCLUSION: Progesterone increased local IGF-I bioavailability in malignant
      breast tissue. That phenomenon depended on steroid receptor phenotype of breast
      tissue and was most evident in tissue expressing progesterone receptor. In non
      malignant tissue that phenomenon was also found in estrogen receptor expressing
      tissue. Lack of steroid receptor expression in breast explants reversed that
      phenomenon.

PMID- 14674123
TI  - [Evaluation of breast conserving therapy (BCT) standards for invasive and
      preinvasive breast cancer adapted in RCO in Bydgoszcz].
AB  - INTRODUCTION: Prophylactic campaign against breast cancer wide spread by Regional
      Center of Oncology made significant influx of patients coming to our place and
      presenting less advanced stages of the mentioned disease. AIM: The aim of this
      work was estimate of BCT treatment standard for invasivum cancer and
      preinvasivunm breast cancer treatment standard which was adapted in RCO.
      MATERIALS AND METHOD: Patients presenting unifocal invasive cancer smaller than 2
      cm, stage No, where the minimal margin of more than 1 cm was possible to perform,
      were qualified to BCT. Minimal surgical border during tumorectomy was 1 cm. We
      were excluded patients with carcinoma lobulare and carcinoma mucinosum. During
      qualification to DCIS treatment standard first we must exclusion multifocalis
      cases based on Anderson classification and Falun consens. In the other cases we
      based on Van Nuys Prognostic Index (VNPI) considering the patient's age. We have
      3 forms of treatment: simplex mastectomy, tumorectomy and tumorectomy with RTG
      therapy. To BCT standard were qualified 52 patients. Schematically was attended
      45 peoples. We had 5 patients which was attended based on preinvasivum breast
      cancer treatment standard. RESULTS: The size of breast cancer tumor at the
      patients which was attended based on BCT standard was 0,5-2 cm. 3 patients was
      disqualified from BCT because we found second breast cancer focus in
      histopathological material. We must widen surgical border post tumorectomy in 5
      cases. Among 5 patients with preinvasivum cancer was 3 simplex mastectomy and 2
      cases tumorectomy with RTG-therapy. CONCLUSIONS: In our opinion BCT treatment
      standard and breast preinvasivum cancer treatment standard should be using only
      in high specialty oncological center. It is a guaranty of right qualification and
      treatment for breast cancer patients.

PMID- 14674124
TI  - Expression of GLUT1 gene in breast cancer cell lines MCF-7 and MDA-MB-231.
AB  - OBJECTIVES: Overexpression of membrane glucose transporters belonging to GLUT
      family, is a common feature of different malignancies. It has been found that the
      level of expression of some members of this large family correlates with
      invasiveness of some malignant tumors. GLUT1 is an example of the most often
      studied and best known members of GLUT receptors. We attempted to compare the
      expression level of GLUT1 gene in two breast cancer cell lines: hormone-positive
      MCF-7 and hormone-resistant, less differentiated and more aggressive MDA-MB-231.
      MATERIALS AND METHODS: A multiplex PCR (after RT) was performed in order to
      semiquantiatively compare differences in the expression of GLUT1 in both cell
      lines. RESULTS: We found a difference in mRNA expression of GLUT1 in two cell
      lines. Densitometric optical analysis of bands resulted in the following results:
      in MCF-7 for GLUT1: 0.624; and in MDA-MB-231 0.875. CONCLUSIONS: In our studies
      we showed differences in GLUT1 receptor mRNA expression in two breast cancer cell
      lines with higher expression in MDA-MB-231. The results show that invasiveness of
      cancer cells may be to some extent associated with the expression of glucose
      transporters, including GLUT1.

PMID- 14674125
TI  - [Value of saline infusion sonohysterography and hysteroscopy in postmenopausal
      patient with persistent abnormal ultrasonographic images after endometrial
      curettage with normal histological results].
AB  - AIM OF THE STUDY: Comparison of sonohysterography vs. outpatients diagnostic
      hysteroscopy in evaluation postmenopausal patient with persistent abnormal
      ultrasounds images after endometrial curettage revealed normal histological
      result. MATERIALS AND METHODS: Material consisted of 47 postmenopausal women age
      44-91 years, diagnosed because of abnormal uterine bleeding and/or suspicious
      endometrial ultrasonographic pictures performed a month after curettage. Patients
      were evaluated by diagnostic sonohysterography (without analgaesia) and
      outpatients diagnostic hysteroscopy (local analgaesia). Outcomes of
      sonohysterography and hysteroscopy were compared with results of histological
      examinations of specimen (hysteroscopical biopsy, hysteroscopical resection or
      hysterectomy). Sensitivity and specificity of two diagnostic methods were
      compared. RESULTS: Intrauterine cause of abnormal ultrasonographic picture was
      disclosed by sonohysterography in 35 (74.46%) cases. Suspicious of focal
      endometrial carcinoma in SIS was reported in 1 (2.12%) case. Sensitivity of SIS
      in relation to all pathology was 0.97, specificity 0.90. Sensitivity and
      specificity amounted in relation to: polyps 1.00 and 0.83, hyperplasia 0.84 and
      0.95. There was no significant statistical differences in sensitivity and
      specificity between SIS and diagnostic hysteroscopy. CONCLUSION: Diagnostic
      hysteroscopy and sonohysterography have the same diagnostic potential in
      evaluation of endometrium. Both methods are useful in patient with unsuspected
      histological results of the specimens. Ultrasonographic pictures imitating
      endometrial carcinoma or endometrial hyperplasia in most cases are connected with
      endometrial polyp. Advantage of applying liquid medium in SIS seems surpass the
      risk of passage of cells of carcinoma to peritoneal cavity.

PMID- 14674126
TI  - [Quantity estimation of the E2/E6 HPV gene products ratio can be a prognostic
      marker for the stage of the cervical cancer carcinogenesis].
AB  - Cervical cancerogenesis is presently considered to be connected with human
      papillomavirus (HPV) infection of cervical epithelial cells. Genomic integration
      of an HPV DNA into epithelial cells is a probable factor increasing cervical
      carcinoma incidence. THE AIM: Of the study was to evaluate the calculated ratios
      of HPV 16 gene amplification products with multiplex PCR. We estimated quantitive
      ratios of HPV 16 genes: E6, E1, E2, and L1. MATERIALS AND METHODS: Ninety three
      cervical carcinoma cases were included into the analysis after detecting DNA
      HPV16 presence in primary lesion. We isolated DNA from cervical smears. RESULTS:
      We discovered statistically significant difference in low E2/E6 (< 0.4)
      amplification ratio patients staged IIa and in stages more advanced than IIa (p =
      0.03). Moreover, we observed high E2/E6 amplification ratio in patients negative
      for lymph-node metastases (according to postoperative pathological report).

PMID- 14674127
TI  - [Radioimmunotherapy in patients with ovarian cancer in complete remission after
      the first line surgery and chemotherapy after second look laparoscopy procedure].
AB  - OBJECTIVES: The aim of the study was analysed a chance to successful
      radioimmunotherapy in patients with ovarian cancer as a consolidation procedure.
      DESIGN: Between 2000 and 2002 we introduced 56 patients into consolidation study
      with radioimmunotherapy after second look laparoscopy. MATERIALS AND METHODS: 17
      patients during screening procedure have failed--mostly with positive CT scans
      (9/17). We have done 39 laparoscopies. Among 11 patients during laparoscopy we
      have found in 6 cases a residual disease and in 5 cases adhesions in abdomen or
      pelvis and this group was excluded from study. The remaining 28 patients were
      divided into two groups--14 in active and 14 in control arm. RESULTS: Only 50% of
      patients with ovarian cancer in complete clinical remission after first line
      surgery and chemotherapy can be candidates to consolidation therapy. Among
      patients subjected to laparoscopy in 70% there was no evidence of macroscopic
      disease and adhesions. CONCLUSIONS: Only 50% patients in complete clinical
      remission after first line surgery and chemotherapy have chance to successful
      radioimmunotherapy.

PMID- 14674128
TI  - [Correlation between transcriptional activity of vascular endothelial growth
      factor (VEFG) and transcriptional activity of its receptors (FLT-1 and FLK-1) in
      low-grade squamous intraepithelial lesions (LSIL) of uterine cervix].
AB  - OBJECTIVES: In this report we focus on angiogenesis, as one component of a
      complex molecular relations in the process of neovascularisation in the low-grade
      intraepithelial changes (LSIL). Increasing number of publications indicates that
      the interrelation between isoforms of VEGF (VEGF121, VEGF145, VEGF165, VEGF183,
      VEGF189, VEGF206) but not total VEGF is responsible for angiogenesis, both in
      physiological and pathological processes. The molecular co-operation of the said
      isoforms and their receptors results in morphological presentation of "de novo"
      created vascular network that dynamically involves the entire connective tissue
      stroma of the uterine cervix. METHOD: The selection of intraepithelial pathology
      38 cases to assess molecular activity of the given genes was based on colposcopy
      examination. Tissue specimens were taken for pathological investigation and to
      analyse transcriptional activity and mRNA alternative splicing of the
      angiogenesis genes. VEGF, Flt-1, Flk-1. To analyse quantitative gene expression
      RT-PCR TaqMan was performed. To estimate the dependence transcriptional activity
      of Flt-1 and Flk-1 on VEGF gene expression Spearman's correlation rank was
      performed. Differences with p < 0.05 were considered significant. RESULTS: The
      comparison of transcriptional activity of VEGF and its receptors revealed
      significant correlation between increase in the number of Flt-1 mRNA copies and
      enhanced mRNA expression of VEGF121 (p < 0.05), VEGF145 (p < 0.05), VEGF165 (p <
      0.05), VEGF183 (p < 0.05), VEGF189 (p < 0.05), and VEGF206 (p < 0.05).
      Significant increase in the number of Flk-1 mRNA copies was observed in case of
      enhanced mRNA expression of VEGF121 (p < 0.05), VEGF145 (p < 0.05), VEGF183 (p <
      0.05), VEGF189 (p < 0.05) and VEGF206 (p < 0.05). The number of sFlt-1 mRNA
      copies significantly correlated only with enhanced VEGF145 mRNA expression (p <
      0.05). CONCLUSION: Changing intensification of transcriptional activity of VEGF
      gene and its receptors indicates on autocrine mechanism regulation of angiogenic
      genes activity in the first steep of carcinogenesis--LSIL.

PMID- 14674129
TI  - [Prophylactic medical examinations for breast cancer and uterine cervix cancer in
      Regional Oncological Center of Bydgoszcz in year 2002].
AB  - OBJECTIVES: Kujawsko-pomorskie province is a region with high morbidity and death
      rate from breast cancer and uterine cervix cancer. One method of improving this
      situation is prophylactic medical examinations aiming to find out the less
      advanced forms. DESIGN: The aim of work was to estimate the results of
      prophylactic medical examinations that were taken in Regional Oncological Center
      of Bydgoszcz during a 2002 year. MATERIALS AND METHODS: Mammography were taken
      using 3 devices. First one so called "mobile" localized in chosen health service
      centres, second in mammobus reaching distant communes and third taking
      examinations locally, where gynaecologic examination and breast examination took
      place. Cytologic examination were rated with Bethesda's system and according to
      Papanicolau. There was 23923 people examined for breast cancer (age 35-79) and
      7946 for uterine cervix cancer (age 30-74). 9183 medical examinations were taken
      by "mobile" device, 4592 in mammobus and 10148 locally. 11986 people had breast
      examination, 6118 had gynaecologic examination. RESULTS: Among cytologic
      examinations results were: I group--3902, II group--4019, III group--21, IV group
      -3, V group--1. Ten uterine cervix cancers were found, that makes 0.13% of
      examined population. Five of them were carcinoma planoepitheliale praeinvasivum.
      Among prophylactic of breast cancer 91 cases were discovered (0.38% of examined
      population). Five of them were carcinoma intraductale typus comedo (3 were
      mastectomy simplex, 2 tumorectomy with radiotherapy). The treatment of invasive
      carcinomas was breast conserving. CONCLUSIONS: Prophylactic medical examinations
      let to find cancer in early state of development, and number of detection of
      carcinomas is a justification of continuation of this project. Possibility to do
      examinations for women from villages should have influence on detection early
      breast cancer and uterine cervix cancer.

PMID- 14674130
TI  - [Surgical complications connected with intraperitoneal chemotherapy in ovarian
      cancer].
AB  - OBJECTIVES: From a theoretical viewpoint, intraperitoneal therapy (i.p.) in
      patients with ovarian cancer, a malignancy, which remains mainly, confined to the
      peritoneal cavity is logical. Intraperitoneal catheters have moved to the
      forefront as a delivery system in cancer treatment. Authors have described
      complications during the placement, usage, and evacuation of Tenckhoff catheters.
      MATERIAL AND METHODS: From January 1996 to January 2003, 118 patients with
      recurrent or persistent ovarian cancer, after surgery and first line
      chemotherapy, have had catheter insertion, but only 91 have had catheter
      evacuation: because of: not complete therapy (21 patients). Three patients died
      during i.p. therapy, Four times intraperitoneal catheter has spontaneously fold
      out. RESULTS: During insertion total number of complications reached (7.63%)--6
      bowel incision, 1 bladder incision, 1 hernia of the linea alba, 1 incision of
      bowel and bladder. During catheter evacuation total number of complications was 9
      (7.63%), 8 bowel incisions, 1 hernia of the linea alba. Complications connected
      with catheter function: only 10 patients required cessation of chemotherapy prior
      to its expected completion because of following reasons: 2 fistula of the
      catheter to vagina, 2 fistulas to bowel, in four cases intraperitoneal catheter
      has spontaneously fold out due to abscess (two after citostatics flow under the
      skin, and two without clear reason probably because of not proper fixation) one
      because of abscess in peritoneal cavity, and problems with citostatics inflow,
      one because of subileus. CONCLUSION: 1 Surgical complications occurring during
      IPC are not dangerous for patients. 2 IPC is valid and safety way of treatment
      ovarian cancer patients. 3 The frequency of complications occurring during
      insertion of Tenckhoff catheter depends on the way of placement. 4 We do not
      noticed connections between frequency of complications and sum of insertion made
      by the surgeon.

PMID- 14674131
TI  - [Intracavitary 500KHZ hyperthermia treatment of patients with endometrial and
      cervical cancer--preliminary clinical and pathological results].
AB  - Therapeutic effectiveness of elevated temperature is a well known issue. However
      raising the temperature inside the tumor sparing concurrently surrounding healthy
      tissue is not an easy task. Intracavitary, radiofrequency hyperthermia in uterine
      tumor cases allows to obtain elevated temperature in a simple, effective and safe
      way. Hyperthermic procedure was performed in 30 patients with cervical and
      endometrial cancer. In 10 cases it was a part of standard radiotherapy, in 20
      hyperthermia proceeded radical surgery. A computer--controlled 300W amplifier and
      generator was used. Energy was transmitted via a modified Fletcher--type
      applicator. One or two 45-60 minute lasting sessions, with temperature reaching
      46-49 degrees C were performed in each case. No severe side effects were seen. In
      a group where surgery was performed a characteristic temperature-induced changes
      were observed on tissue and cellular level. Higher number of performed procedures
      will be a base for randomized trials and, in the future enables us to incorporate
      hyperthermia into standard radiotherapy.

PMID- 14674132
TI  - [Lymph node mapping and sentinel node detection in carcinoma of the cervix,
      endometrium and vulva].
AB  - OBJECTIVES: Validity of the sentinel node concept in patients with cervical,
      endometrial and vulvar cancer. MATERIAL AND METHODS: 47 cases of FIGO stage I and
      II cervical cancer, 33 cases of first clinical stage of endometrial cancer and 37
      patients with FIGO stage I and II of vulvar cancer. In cervical and vulvar cancer
      preoperative lymphoscyntygraphy and intraoperative lymphatic mapping with blue
      dye and handheld gamma probe were performed. In patients with endometrial cancer
      intraoperative lymphatic mapping with blue dye injected into the cervix and into
      the uterine corpus subserously were done. In the last 10 cases radiolabeled
      nannocolloid were administered and the patients underwent preoperative
      lymphoscyntygraphy and intraoperative radio detection of sentinel node. Sentinel
      nodes were labeled as blue, radioactive, or blue/radioactive. RESULTS: In
      cervical cancer sensitivity of the dye and radiocolloid methods was 94%,
      specificity 100% and negative predictive value 97%. Out of 33 cases of
      endometrial cancer sentinel node was identified in 29 (87.87%) patients. None of
      women with histological negative sentinel node had metastases in the rest of
      lymph nodes resected. Sentinel node was detected in all cases of vulvar cancer.
      The status of sentinel nodes were representative for all lymph node resected.
      CONCLUSIONS: Concept of sentinel node may be applied first of all for vulvar
      cancer and also for cervical and endometrial cancer.

PMID- 14674133
TI  - [Treatment of hyperplasia endometrium with GNRH agonists].
AB  - OBJECTIVES: Untreated hormonal disturbances connected with unbalanced estrogen
      serum concentrations can influence on pathological proliferation of endometrium.
      The aim of the study is to assess the effect of GnRH agonists on endometrium in
      women consulted due to simple hyperplasia endometrium. MATERIAL AND METHODS: 15
      women in the mean age 48.5 +/- 3.5 years with the histopathological diagnosis of
      simple hyperplasia were treated with trioptorelin during 3 months. After therapy
      all patients were undergone transvaginal ultrasonography and endometrial biopsy.
      RESULTS: Atrophic endometrium were observed in all women after a 3-month therapy.
      The thickness of endometrium decreased from 10.21 +/- 3.2 mm to 3.94 +/- 1.56 mm.
      CONCLUSIONS: The efficacy of the therapy of simple hyperplasia in women with GnRH
      agonist was 100%.

PMID- 14674134
TI  - [Germinal cell tumors in young and adolescent girls].
AB  - OBJECTIVE: Germ cell tumours are the most common ovarian tumours in childhood and
      adolescence. This diverse group of tumours derives from germ cells. DESIGN: The
      aim of this work is presentation of germ cell tumours in the material from our
      clinic with characteristic clinical features, the scope of operation and effects
      of many years of observation. MATERIALS AND METHODS: We treated 109 girls with
      germ cell tumours of the ovary: 13 had malignant tumours: there were 7 patients
      with dysgerminomas, 2 with endodermal sinus tumour of the ovary, 3 with immature
      teratomas, 1 with carcinoma embryonale. Gonadoblastomas was diagnosed 4 patients
      and mature teratomas in 92 patients. RESULTS: 11 patient had gonadal dysgenesia
      with abnormal karyotype. These girls had no follicle apparatus in gonads and had
      elevated levels of gonadotropins. Gonadoblastoma is almost always found in
      patients with gonadal dysgenesis. Gonadoblastoma often produces estradiol or
      testosterone. There can be problems with diagnosis of the syndrome, because
      developmental features imitate the onset of normal puberty. Most patients with
      dysgerminoma have stage I of disease and surgery is sufficient. It must be
      suggested that patients of stage I who wish to preserve childbearing function may
      be treated with unilateral salpingoophorectomy and adjuvant chemotherapy.
      Monitoring of the treatment is connected with measurement of biochemical markers.
      Some of these markers are useful for monitoring of response to therapy. When
      levels of markers are low second look laparoscopic operation should be performed.
      Cytological smears and biopsy specimens from the remaining ovary, peritoneum and
      subdiaphragmatic area should be obtained laparoscopically. CONCLUSIONS: The sift
      ultrasonographic investigations can be helpful in the early diagnosis of germ
      cell tumours of the ovary in girls. Absence of follicle apparatus in the gonads
      requires determination of levels of gonadotropins and karyotype. Fertility
      sparing operative treatment is preferred when karyotype is normal.

PMID- 14674135
TI  - [Analysis of physiologic and abnormal pictures of uterine cervix by means of
      infrared thermography].
AB  - RATIONALE FOR THE STUDY: Diagnosis of the uterine cervix lesions remains a key
      element of the women's health care especially in the context of the cervical
      carcinoma prophylaxis. The infrared mapping constitutes a new generation
      biophysical diagnostic method of potential application in medicine. OBJECTIVE:
      The study was planned to analyze uterine cervix thermograms in both physiology
      and pathology of this organ. An attempt was made to establish the standard
      thermographic pattern of the portion. MATERIAL AND METHODS: The study population
      consisted of 51 women aged from 20 do 70 years. In total, 109 thermographic
      patterns were analyzed by the computer processing of the thermovision data. In
      order to establish a physiologic standard, 14 thermograms of the normal cervix
      were analyzed in detail. Furthermore, thermograms of such cervical lesions as
      endocervical polyp (3 patients), erosion (PAP II) (11 cases), CIN I-III (9
      patients) and invasive cancer (6 patients) were studied. The diagnosis was based
      on clinical, cytologic and colposcopic criteria as well as on the pathology
      report. The infrared camera AGEMA AGA-880 and the specialized software was used.
      The measurements were done in a standardized climatic environment. RESULTS:
      Comparisons between the studied groups revealed significant differences between
      invasive cervical cancer and benign lesions or healthy cervix. Significant were
      also differences in mean temperature and highest temperature for all the studied
      groups. The difference in mean whole portion temperature between the normal
      cervix and invasive planoepithelial cancer amounted to 1.4 degrees C while in
      comparison to other lesions it did not exceed 0.5 degree C. Statistical analysis
      of the averaged profiles of cervical temperatures has also shown significant
      differences between invasive cancer and the remaining groups--by 1.5 degrees C in
      average. Strong interrelationships (p < 0.001) were found among the single
      results of thermography measurements within all the groups. The thermographic
      profiles of all 14 thermograms of normal portion did not exceed the two standard
      deviations range of the established standard with the mean temperature of 36.56
      degrees +/- 0.56 degree C. CONCLUSIONS: 1. The established thermographic mapping
      patterns of the normal cervix may form a basis for the future evaluation of the
      diagnostic application of computer thermography in gynecology. 2. Statistically
      significant differences were found in thermographic profiles of the portion
      between the normal cervix and such cervical lesions as endocervical polyp,
      erosion (PAP II), CIN and invasive cancer. 3. Invasive cervical cancer reveals
      thermographic pattern of relatively high specificity within the analyzed cervical
      lesions.

PMID- 14674136
TI  - [Use of multilayer perception artificial neutral networks for the prediction of
      the probability of malignancy in adnexal tumors].
AB  - BACKGROUND: Advanced statistical methods are currently are more often used in the
      prediction of ovarian malignancy when adnexal tumor is detected. These methods
      include logistic regression analysis and artificial neural networks (ANN's), i.e.
      computer programs which are capable of learning from presented data and further
      predict various events, such as clinical diagnosis or outcome of a given
      treatment. MATERIALS AND METHODS: We have analyzed data of 307 women with adnexal
      tumors who were operated in the Ist Dept. of Gynecology, Medical University in
      Lublin between 2000-2002. Following clinical and sonographic variables were
      included: age, menopausal status, serum CA-125, bilaterality, tumor size and
      volume, papillary projections, septa, solid parts presence, Doppler blood flow
      indices (PI, RI, Vmax), and subjective-color Doppler score. A multiple layer
      perceptron (MLP) neural network with 13 input variables, 11 hidden neurons and
      one output variable was constructed to assess probability of malignancy in each
      women (Statistica v. 6.0 for Windows, Statsoft, USA). Sensitivity, specificity
      and accuracy of the model were calculated. Receiver-Operating Characteristics
      curves were generated and corresponding Areas Under ROC Curves (AUROC's) for all
      diagnostic tests were compared. RESULTS: Final histologic examination revealed
      228 (74.3%) benign tumors and 79 (25.7%) malignant masses including 21 women with
      FIGO stage I ovarian cancer. With a 75% cut-off probability of malignancy level
      the sensitivity and specificity of the best network in the testing set was 96.7%
      and 100%, respectively. In the validation set the corresponding values of
      sensitivity and specificity were 82.3% and 97.5%. The highest of all used tests
      AUROC equal to 0.9749 was found for the ANN predictive model. CONCLUSIONS: ANN
      may help in the extraction of the most useful predictive clinical and ultrasound
      data. The sensitivity and specificity of the ANN's generated model were higher
      than currently used single clinical and diagnostic tests. However, a prospective
      testing in a new, much larger group of women with adnexal tumors is essential for
      the clinical usefulness of the proposed statistical model.

PMID- 14674137
TI  - [Characteristics of ovarian tumors with color Doppler sonography: a comparison of
      predictive models derived from two academic centers data].
AB  - OBJECTIVE: To construct and cross-validate logistic regression models used for
      the prediction of ovarian malignancies in two groups of women with adnexal
      tumors. MATERIALS AND METHODS: Preoperative clinical, gray-scale and color
      Doppler ultrasound data of 307 women treated in the Ist Dept of Gynecology of the
      Medical University in Lublin (group I) and 464 of women treated in the Dept of
      Surgical Gynecology, Medical University in Poznan (group II) were analyzed
      retrospectively. These data were used to construct predictive models which were
      developed for both groups separately and then cross-validated (12 cases in each
      group, six malignant and 6 benign) between the groups. Multiple logistic
      regression analysis was chosen to calculate probability of malignancy in each
      examined mass. RESULTS: There were 228 (74.2%) benign tumors and 79 (25.7%)
      malignant tumors in group I. Group II consisted of 299 (64.4%) benign tumors and
      165 (35.6%) malignant masses. Only six variables were included in the logistic
      regression model in group I. These were age, bilaterality, septae, papillary
      projections, volume and color score. In group II there were also 6 variables
      included in the regression model (menopausal status, septae, bilaterality,
      ascites, blood vessel localization and PI). At 50% probability of malignancy the
      model constructed for group I had a sensitivity and specificity of 74.6% i 94.7%,
      respectively. At the same probability level in group II sensitivity and
      specificity were 86.1% i 93.6%, respectively. Cross-validation of the predictive
      model constructed for group I in randomly selected cases from group II had
      sensitivity of 66.4% and specificity of 79.2%. Sensitivity and specificity of the
      group II model tested in cases from group I were 64.3% and 75.2%, respectively.
      CONCLUSIONS: We conclude that predictive models created with the use of multiple
      logistic regression analysis may be useful in preoperative discrimination of
      adnexal tumors. However, much better definition of diagnostic criteria,
      especially color Doppler score must be achieved before these models could be
      widely used in clinical practice.

PMID- 14674138
TI  - [Usefulness of logistic regression model to predict the endometrial carcinoma
      based on blood flow indices measured wit the of three-dimensional Doppler
      sonography].
AB  - AIM: Construction and prospective verification of predictive model permitting to
      rate individual probability of existence of endometrial carcinoma with use of
      three-dimensional Doppler Doppler sonography. MATERIAL AND METHODS: We analyzed
      the results of 3D sonography of 123 women (mean age 53.8 +/- 10.6; mean BMI--28.2
      +/- 5.4). We estimated: endometrial thickness and volume, blood flow indices. All
      ultrasound measurements were verified by histology. In aim of finding the best
      combination of features essentially affect on endometrial cancer's risk and for
      estimate individual probability of endometrial cancer we use a logistic
      regression analysis. The obtained model was verified on 20 new cases. RESULTS:
      There were 24 women with endometrial cancer, 59 women with endometrial
      hyperplasia and 40 women without endometrial changes. We affirmed that only three
      variables had statistical significant influence on the constructed predictive
      model. Probability of endometrial carcinoma was: P(X) = 1/(1 + e-z), where "e" is
      mathematical constant and z = 0.12 x age + 0.16 x endometrial thickness + 0.47 x
      VI -11.3. The best sensitivity and specificity were 70.8% and 98.9%. The
      sensitivity and specificity in 20 new cases was adequately 75% and 91.6%.
      CONCLUSION: The usefulness of a predictive model built with the help of logistic
      regression analysis increase sonographic diagnostic precision. The usefulness of
      endometrial blood flow indices permit to estimate the individual risk of
      endometrial cancer in women examined with three-dimensional sonography.

PMID- 14674139
TI  - [Evaluation of predictive value of the ultrasound Doppler's scale in
      determination of the ovarian tumors malignancy].
AB  - Ultrasound examination with the use of the transvaginal probe is extremely
      important among early detection methods of the ovarian tumors. Application of the
      Doppler's technique makes it possible to evaluate vascularity of the tumors in
      the light of malignancy prognosis. AIM: Evaluation of predictive value of the
      suggested Doppler's Scale (DS.) detecting preoperative degree of the ovarian
      tumor malignancy. PATIENTS AND METHODS: The analyses involved data obtained in
      evaluation of 464 ovarian tumors of women treated in Gynecology and Obstetric
      Clinical Hospital of the Karol Marcinkowski University of Medical Sciences,
      Poznan, Poland in the years 1994-2002. As a result of histopathological
      examination, 165 patients had a malignant ovarian tumor detected, and other 299
      were found to suffer from a benign tumor. Predictive values among the scrutinized
      group of women were also analyzed in respect of their menopausal status by
      determining appropriate values for women before and after menopause. The obtained
      data allowed to draw ROC curves and to compare diagnostic value of the suggested
      scale for the groups of patients under the scrutiny. Evaluation involved: number
      of vessels, their location and arrangement, shape of velocity waves as well as
      presence of the protodiastolic notch in the arterial vessels of the tumor. Each
      of the mentioned features could acquire a point-value of 0 or 1. RESULTS: A cut
      off point for the suggested Doppler's evaluation scale of the ovarian tumors
      vascularity was determined at the level of 4. The following predictive values
      were obtained: [table: see text] CONCLUSIONS: Tumor features analyses as a result
      of ultrasound Doppler's evaluation enables precise prognosis of the malignancy
      degree. The suggested point-scale concerning the most significant elements of the
      Doppler's half-amount analyses facilitates precise determination of the
      malignancy degree of the ovarian tumors and enables selection of the most
      effective of therapeutic treatment. The technique is a precious supportive tool
      in the preoperative detection of the ovarian tumors malignancy.

PMID- 14674140
TI  - [Neo-angiogenesis in immunohistochemical techniques as a prognostic factor in
      endometrial carcinoma].
AB  - OBJECTIVE: Angiogenesis in malignant tumors is a prognostic factor associated
      with tumor growth and metastasis. The aim of the research was: determination of
      the angiodensity rate in two immunohistochemical techniques, estimation of the
      value of the examined parameter at different stages of clinical progression and
      histological differentiation of endometrial carcinoma, and analysis of the
      obtained values as prognostic factors in the disease process. MATERIALS AND
      METHODS: The examination covered 86 women treated surgically for endometrial
      carcinoma. The preliminary histological evaluation was followed by
      immunohistochemical methods. The microvessels within the invasive cancer were
      highlighted by means of immuno-cytochemical staining to detect CD-31 and CD-105
      antigen. The average value of angiodesity was estimated by means of a computer
      image analyser. RESULTS: The group of patients at the preinvasive stage of the
      disease manifested significantly statistically lower values of angiodensity. It
      was detected that the histological differentiation of carcinoma does not
      influence intensification of angiogenesis. Higher values of this parameter have
      an adverse influence on the survival rate. CONCLUSION: The evaluation of the
      angiodensity coefficient can be a helpful prognostic parameter in endometrial
      carcinoma.

PMID- 14674141
TI  - [Hysteroscopic evaluation of the uterine cavity in postmenopausal women with
      uterine bleeding].
AB  - Postmenopausal uterine bleeding is the most characteristic and frequent
      endometrial adenocarcinoma symptom. Patient with uterine bleeding appeared at
      least 12 months after the last menstruation needs diagnostic management before
      initiation of any treatment. OBJECTIVES: Evaluation of hysteroscopy for the
      recognition of pathologies causing postmenopausal uterine bleeding. MATERIALS AND
      METHODS: Seventy-nine women aged 48-80 without hormonal replacement therapy
      hospitalized in the 1st Department of Gynecology and Gynecological Oncology of
      the Medical University of Lodz between 1998-2002 because of postmenopausal
      uterine bleeding were included in the study. In each case diagnostic hysteroscopy
      with visualisation of the uterine cavity was performed and then histopathologic
      biopsy by a curretage was taken. Hysteroscopic images were analyzed and compared
      with the histopathological results. RESULTS: 2 women had the oncologically
      suspected hysteroscopic images. In both cases endometrial adenocarcinoma was
      histopathologically confirmed. Among 5 patients with hysteroscopic images
      suggesting non-malignant endometrial proliferation 4 cases of endometrial
      hyperplasia were found. 11 times hysteroscopic visualisation of endometrial
      polyps enabled their complete deletion. In 8 cases intrauterine adhesions were
      found and dissected: 11 patients presented submucous myomas during hysteroscopy.
      In 3 cases visualisation of the uterine cavity was not possible because of
      technical failure. Any patient with absence of hysteroscopically found uterine
      abnormalities had a poor histopathological result. CONCLUSIONS: Hysteroscopic
      investigation in postmenopausal women with uterine bleeding reduce the risk of
      false negative histopathological result. Hysteroscopy is useful method of the
      uterine cavity visualisation. Thanks to localization and elimination of the
      pathologies like endometrial polyps and intrauterine adhesions the repeated
      bleeding and the second time admission of the patient for the same reason can be
      avoided.

PMID- 14674142
TI  - [Evaluation of wild-type estrogen receptor beta and its isoforms: ER-beta/delta
      5/6 i ER-beta/delta 6 in endometrial adenocarcinoma].
AB  - Estrogen target genes play essential role among pathogenetic and prognostic
      factors of endometrial adenocarcinoma; and among them estrogen receptor genes.
      Although prevailing estrogen receptor type is ER-alpha in endometrium,
      transduction of signal carried by estrogens can be also mediate by ER-beta, which
      biological meaning relies on modulation of ER-alpha transcriptional activity.
      There is hypothesized that ER-beta can keep under control mitogenic activity
      mediating by ER-alpha. The aim of the study was qualitative and quantitative
      analysis of wtER-beta and ER-beta/delta 5-6, ER-beta/delta 6 isoforms in
      endometrial adenocarcinoma. Material used in the study included specimens
      obtained from 27 female: group I--normal endometrium (n = 12), group II-
      endometrial adenocarcinoma (n = 15). RNA was extracted from the analyzed material
      using phenol-chloroform method by Total RNA Prep Plus. Qualitative analysis was
      performed basing on RT-PCR reaction and polyacrylamide gel electrophoreses. For
      all RNA extracts of the samples examined RT-PCR was performed with a sequence
      detector ABIPRISMTM7700--Perkin-Elmer Applied Biosystems (RT: 600 C-30 min; PCR:
      950 C-5 min, 40 cycles: 950 C-30s, 600 C-1 min, and 720 C-10 min) in order to
      determine the number of RNA copies (which corresponds to the number of cDNA
      copies) for wtER-beta and ER-beta/delta 5-6 and ER-beta/delta 6. Specificity of
      QRT-PCR reaction was determined by delimitation of melting temperature of all
      examined amplimers (ABI PRISM7000, Qu-antiTect SYBR Green RT-PCR Kit) and by
      sequence analysis using ABI PRISM377 DNA Sequencer. Wild-type of estrogen
      receptor beta and ER-beta/delta 5-6, ER-beta/delta 6 isoforms--coming into
      alternative splicing of mRNA, presented both, in proliferative endometrium and
      endometrial adenocarcinoma. Copy number of wtER-beta mRNA was significantly (p <
      0.05, Mann-Whitney U test) lower in comparison with proliferative endometrium and
      correlated with decrease of ER-beta/delta 6 mRNA copy number (r = 0.85; p <
      0.05). Preliminary results confirming decrease of wtER-beta, ER-beta/delta 5/6
      and ER-beta/delta 6 mRNA copy number in endometrial adenocarcinoma can show their
      relationship with high risk of carcinogenesis.

PMID- 14674143
TI  - [Profile of estrogen receptor alpha isoforms in endometrial adenocarcinoma].
AB  - Affectivity of activity of wild-type estrogen receptors forms depends not only
      from transcriptional activity of their encoding genes, but also from
      participation of ERs isoforms in entire ERs mRNA pool. Estrogen receptor mRNA
      isoforms are essential intracellular factor regulating cellular answer of
      estrogen. ERs expression, as well as the mRNA splice variants, may influence the
      biological properties of some tumors and affect their ability to respond to
      estrogen and antiestrogen therapies. The aim of the study was qualitative and
      quantitative analysis and comparison of mRNA ER-alpha and their isoforms
      concentration profile in endometrial adenocarcinoma and normal endometrium as
      control group. The level of ER-alpha mRNA was estimated using RT-QPCR method in
      proliferative phase (n = 12) and endometrial adenocarcinoma (n = 15). Types of
      alternative mRNA ER-alpha splice variants were marked. Seven transcripts ER-alpha
      (ER-alpha/delta 2, ER-alpha/3, ER-alpha/delta 2-3, ER-alpha 4-ER-alpha/delta 7)
      were quantitatively evaluated. Proportional analysis of particular mRNA ER-alpha
      isoforms participation in entire pool of mRNA ER-alpha showed diminution of ER
      alpha/delta 2, ER-alpha/delta 2-3, ER-alpha/delta 7 what correlated with
      simultaneous decrease of mRNA copy number in endometrial adenocarcinoma.
      Endometrial adenocarcinoma was also characterized by presence of isoforms not
      stepping out in investigated segments of normal endometrium: ER-alpha/delta 4, ER
      alpha/delta 6 and ER-alpha/delta 5 being with factor about high transcriptional
      activity potential, are able to activate transcription of estrogen receptors
      target genes independently from ligad binding. Additional ER-alpha isoforms
      appearing in endometrial adenocarcinoma instead of wild-type ER? proves, that in
      chance of tumor transformation the number of potranscriptional modifications
      increases. One can not exclude that their number is connected with genetic
      changes starting carcinogenesis in endometrium. Changes of mRNA ER-alpha copy
      number and presence of definite isoforms may altered of signaling estrogen
      pathways.

PMID- 14674144
TI  - [Thymidine phosphorylase activity and neo-angiogenesis in ovarian cancer].
AB  - Neo-angiogenesis seems to play an important role in the progression of ovarian
      cancer and in formation of distant metastases. Data from literature on role of
      phosphorylase in neoplasmatic disease and in neo-angiogenesis are controversial.
      In mammalian cytosole there are two different pirymidine nucleosyde
      phosphorylases: thymidine (PT) and uridine (PU). Both of them play important role
      in the metabolism of nucleosides as well as in the recycling of pyrimidine base.
      Recently thymidine phosphorylase is identified with platelet derived endothelial
      cell growth factor (PD-ECGF). It has been demonstrated, that PD-ECGF/PT influence
      on neo-angiogenesis and correlates with degree of neoplasmatic invasion. In
      literature the data about thymidine phosphorylase activity and its correlation
      with neoplasmatic angiogenesis in ovarian tumors are controversial. The aim of
      the study was to evaluate the activity of PT together with the intensity of
      angiogenesis in epithelial ovarian tumors. 42 patients with ovarian cancer were
      included into the study. The enzyme activity was measured in ovarian cancer
      tissue and in the serum in the spectrophotometer. Intratumoral microvessel
      density (IMD) was evaluated in tumor using immunohistochemical methods. 10 woman
      with normal ovaries, treated surgically due to non-oncological reasons served as
      a control. Activity of PT in ovarian tumor and in serum was compared to the
      control group. Correlation between the intensity of angiogenesis and PT activity
      in ovarian cancer was also investigated. Significantly higher PT activity was
      stated both in tumor and serum when compared to the control. Positive correlation
      between enzyme activity in the serum and neoplasmatic tissue was found.
      Surprisingly, the negative correlation between neo-angiogenesis and PT activity
      in ovarian cancer was observed. Neo-angiogenesis is higher in ovarian cancer,
      when compared to the group of borderline malignancy tumors. Positive correlation
      between PT activity and staging in ovarian cancer was observed. No correlation
      between grading and histopathological type of epithelial cancer was observed. PT
      activity and neo-angiogenesis evaluation might be useful in diagnostics of
      ovarian cancer.

PMID- 14674145
TI  - [Laboratory investigation of flow characteristics during intraperitoneal
      hyperthermic perfusion chemotherapy].
AB  - OBJECTIVES: Intraperitoneal hyperthermic perfusion chemotherapy (IPCH) is a
      complex method used for the treatment of the ovarian cancer. During the
      procedure, chemotherapeutic agent is administrated into the peritoneal cavity
      using continuous perfusion and hyperthermic conditions. DESIGN: This experiment
      was performed to simulate the main features of IPCH and to determine the
      hydrodynamic characteristics of this method in the laboratory conditions.
      MATERIALS AND METHODS: The model was made in a natural scale, regarding the
      anatomical proportions. In order to establish the dispersive properties of the
      model we determined the distribution of the tracer as a function of the drains'
      location and intensity of flow. RESULTS AND CONCLUSIONS: The important practical
      conclusion of the study is that the most advantageous variant is 'slanted'
      location of inflow and outflow drains. It is also possible to confirm that the
      hydrodynamic features applied during IPCH enable adequate drug distribution in
      the peritoneal cavity. The employed location of drains could be reconsider
      including the possibility of introducing cyclic flow direction alteration
      (increasing the dispersive properties of the system). We would like thank the
      Department of Cardiacthoracic Surgery, Rigshospitalet, Copenhagen, Denmark for
      lending the peristaltic pump.

PMID- 14674146
TI  - [Clinical and cytogenetic evaluation of patients with disorders of somato-sexual
      development].
AB  - Congenital somato-sexual disturbances include wide range of classic syndromes, as
      well as different types of numerous or isolated developmental defects. 28 women
      with disorders of sexual development were clinically and cytogenetically
      analyzed. AIM: Clinical and cytogenetic evaluation of patients with disorders of
      somato-sexual development. MATERIAL AND METHODS: 28 women, 17-35 years old, were
      included in the study. Analysis data were performed on the basis of clinical
      records from Department of Obstetrics and Woman's Diseases of Medical University
      in Bydgoszczy. Cytogenetic investigations were carried out on standard lymphocyte
      culture method. RESULTS: Turner's syndrome was found in 12 women; 45, X in 7
      mosaic karyotype 45, X/46, XX in 4, isochromosome i(Xq) in 1.3 women had normal,
      male karyotype, 46, XY. One of them had dysgenetic gonads of malignant dysplesia
      transformation. One patient's karyotype was 47, XXX. 12 women with gonadal
      dysgenesis--karyotype 46, XX. CONCLUSIONS: 1. Patients with congenital disorders
      of somato-sexual development are a heterogenous group. 2. Laparoscopy an
      effective diagnostic and treatment method in women with disorders of congenital
      somato-sexual development.

PMID- 14674147
TI  - [Analysis of complications of the tension-free vaginal tape procedure for
      surgical treatment of female stress urinary incontinence].
AB  - OBJECTIVE: The most common types of urinary incontinence in women are stress,
      urge and mixed incontinence. Stress urinary incontinence may be caused by an
      urethral hypermobility and internal sphincter deficiency (ISD). There are over
      100 different surgical procedure for the treatment of female stress incontinence.
      Tension-free vaginal tape (TVT) is a new anti-incontinence surgical technique
      which was first described by Ulmsten in 1996. The aim of the study was to
      evaluate the complications of tension-free vaginal tape (TVT) for the surgical
      treatment of female stress incontinence. METHODS: The study group was consisted
      of 162 women, aged 32-84. All patients had a basic evaluation that included a
      history, frequency/volume chart, questionnaire of micturition (self-made),
      physical examination, stress test, Bonney test, urinalysis and bacterial culture
      of urine. Women with mixed urinary incontinence and who underwent surgical
      treatment of SUI in the past had been done urodynamic investigation. The
      operation was carried out under epidural, subarachnoid and general anesthesia.
      The TVT procedure was performed as described by Ulmsten. The follow-up was done
      after 1 day, 1 and 3 and 6 months since the operation. RESULTS: Among
      complications related to the procedure were 11 cases of cystotomy, 5 cases of
      urinary retention requiring four days catheterization, 3 cases of bleeding from
      the vagina, 14 cases of detrusor instability de novo. In 4 cases occurred
      postoperative obstinate pain. In 4 cases occurred recurrent urinary tract
      infection. None complication required invasive treatment. No evidence of defect
      healing or rejection of the tape was found. CONCLUSIONS: We conclude that the TVT
      procedure is safe method of the surgical treatment of urinary stress incontinence
      associated with a low complications.

PMID- 14674148
TI  - [Effects of simvastatin only or in combination with continuous combined hormone
      replacement therapy on lipid levels in hypercholesterolemic women].
AB  - OBJECTIVE: To evaluate the effects of simvastatin only or combined with
      continuous transdermal hormone replacement therapy (HRT) on the serum lipid
      profile in hypercholesterolaemic women. MATERIAL AND METHODS: The study
      population consisted of 75 women after menopause, ranging in age from 45 to 62.
      The patients were divided into five groups: group I--women receiving HRT (Systen
      Sequi, Cilag); group II--HRT + statin (Systen Sequi, Cilag + Zocor, MSD); group
      III--HRT (Systen Conti, Cilag); group IV--HRT + statin (Systen Conti, Cilag +
      Zocor, MSD) and group V--statin only (Zocor, MSD). Before and after 3 and 6
      months therapy serum total cholesterol (TC), triglycerides (TG), HDL-cholesterol
      (HDL-C) and LDL-cholesterol (LDL-C) was measured. RESULTS: The combination of
      simvastatin + HRT or simvastatin only decreased significantly TC and LDL-C, and
      increased HDL-C levels at 3 months (groups II, IV and V). A comparative analysis
      revealed that HRT effect on TC, LDL-C and HDL-C was significantly observed after
      6 months (group I and III). TG levels significantly decreased after 6 months of
      therapy (simvastatin + HRT) in groups II and IV. CONCLUSIONS: The combination of
      simvastatin and HRT seems to be more effective than simvastatin only in the
      treatment of hypercholesterolaemia in women.

PMID- 14674150
TI  - [Homocysteine level in ovarian follicular fluid or serum as a predictor of
      successful fertilization].
AB  - OBJECTIVES: There are some data concerning homocysteine influence on
      fertilization and early embryogenesis, especially in women experiencing recurrent
      pregnancy loss (RSA). However, limited data support hypothesis that the ovum
      might be exposed to high homocysteine concentration what may be important in egg
      sperm interactions, for example during in vitro-fertilization (IVF) cycle.
      DESIGN: Therefore, the aim of our study was to determine fasting total
      homocysteine concentration in follicular fluid or serum of women experiencing
      reproductive failure after spontaneous or in-vitro fertilization. MATERIALS AND
      METHODS: Eight nonpregnant RSA women, 8 normal healthy women with previous
      successful pregnancy outcome and 15 women undergoing IVF (6 with unexplained
      infertility-UI, 6 with male factor-MF, 3 with tubal obstruction-TO). Total
      fasting homocysteine level concentrations were established by ELISA method (Axis
      Homocysteine EIA, Axis-Shield AS) in serum of RSA and normal healthy women or
      ovarian follicular fluid of women undergoing IVF. RESULTS: Mean fasting total
      homocysteine concentration in study group were as follows: RSA-18.63 mumol/L +/-
      6.67, Normal-13.98 mumol/L +/- 6.62, UI-20.62 mumol/L +/- 8.19, MF-22.60 mumol/L
      +/- 7.87, TO-36.75 mumol/L +/- 13.26. We found that RSA women have had
      significantly higher serum homocysteine concentration when compared to normal
      healthy women (P < 0.05). Among women undergoing IVF, those with following IVF
      success had not significantly lower homocysteine level when compared to those
      with IVF failure (22.81 mumol/L +/- 11.27 vs. 24.54 mumol/L +/- 9.50, P > 0.05).
      CONCLUSIONS: Our preliminary data suggest that high homocysteine level may
      negatively influence pregnancy outcome following natural or in-vitro
      fertilization. It cannot be excluded that elevated homocysteine concentrations
      contribute to defective chorionic villous vascularization during early stages of
      gestation.

PMID- 14674149
TI  - [Protocol of GNRH antagonist in poor responders in IVF-ET cycles].
AB  - INTRODUCTION: Response to stimulation is one of the factors that affect the
      results of infertility treatment in IVF-ET cycles. Poor responders as well as the
      occurrence of ovulation prior to the oocyte retrieval is a main reason of nearly
      30% of cancellations of the treatment cycles. In poor responders high doses of
      gonadotrophins are sometimes required. However administration of gonadotrophins
      alone does not prevent premature LH surge. The aim of the study was to assess
      controlled ovarian stimulation protocols with GnRH antagonists (Cetrotide) in
      poor responders. MATERIAL AND METHODS: The study group consisted of 27 infertile
      women, mean age 35.8 (range 28-45) undergoing the second IVF cycle. In those
      women the first cycle was either cancelled due to the lack of follicles'
      development or the small number of growing follicles (1-2). Ovarian stimulation
      was started on the 2 day of cycle with administration of 225 IU or rFSH or hMG.
      Cetrotide was administered subcutaneously in a daily dose of 0.25 mg starting
      when estradiol serum concentration reached 150 pg/ml with a lead follicle 14 mm
      diameter and continued throughout the gonadotrophin treatment until HCG
      administration. RESULTS: In 31 cycles the mean number of MII oocytes retrieved
      was 4.71 (range 1-10). In one woman there was no mature oocytes obtained during
      pick-up. In one case the cycle was cancelled due to the bad response. The mean
      duration of cetrotide administration was 5.16 days. The mean number of rFSH and
      HMG ampoules was 23 and 30 respectively. The fertilisation rate was 64%. Embryo
      transfer was performed on the 3rd day after pick-up. The pregnancy rate in this
      group was 22%. There weren't any adverse effects of Cetrotide in treated women.
      No case of ovarian hyperstimulation syndrome occurred. CONCLUSION: Ovarian
      stimulation protocol with GnRH antagonist is effective in poor responders in IVF
      ET cycles.

PMID- 14674151
TI  - [Artificial reproductive techniques: comparison of embryo transfer on day two or
      day three].
AB  - OBJECTIVES: Due to the lack of adequate media which could support embryo in vitro
      development in early IVF procedure day 2 transfer has been a dominated procedure.
      However, day 3 transfers more physiological to in vivo conditions and may pre
      select embryos with better prognosis. MATERIALS AND METHODS: A studied group was
      131 infertile couples subjected to classical IVF or ICSI in proportion, and day 2
      transfer was performed in 67 cycles, while day 3 transfer in 64 cycles. Average
      age of both groups was comparable--around 31 years of age. In all cycles the long
      protocol of stimulation was applied. For in vitro culture--MediCult (Denmark)
      medium was employed. RESULTS: There were no statistical differences in proportion
      of class A to B embryos in a group with day 2 transfer (respectively: 65.2% and
      30.4%) and in a group with day 3 transfer (respectively: 63.5% and 30.8% for A
      and B embryos). Similar rates of pregnancies per cycle were obtained--25.4% and
      25.0% respectively for day 2 and day 3 transfer. There were also no statistical
      differences in implantation rate per cycle (28% and 27% respectively).
      CONCLUSIONS: Performed analysis did not allow to indicate statistical significant
      differences in laboratory and clinical data for both studied groups. However,
      retrospective study does not exclude subjective criteria that could be applied to
      individual will of the patient regarding a day of transfer.

PMID- 14674153
TI  - [Brief report about the establishment and activity in the first years of the
      Cracow Gynecological Society].
AB  - The Cracow Gynaecological Society is the oldest functioning society in Poland. It
      was established in 1889. The paper introduces the circumstances related to the
      foundation of the society including a number of new yet unknown facts.

PMID- 14674152
TI  - [Innate immunity participation in the pathogenesis of endometriosis].
AB  - Endometriosis is a serious clinical problem among the women treated because of
      gynecological reasons. The frequency of its occurrence is estimated for 10-15% of
      all women at reproductive age. AIM: This study evaluates the chosen phenomenons
      participating in innate immunity and their role in the pathogenesis of
      endometriosis. MATERIALS AND METHODS: 42 patients aged 22 to 39 years old treated
      in Surgical Gynecology Department of Polish Mother Health Centre Research
      Institute were the study group. Comparative group consisted of 22 age-matched
      women with no clinical complains. We evaluated production of reactive oxygen
      intermediates by peripheral blood neutrophils in both groups of women (both
      spontaneous and stimulated with fMLP) using the chemiluminescence test. We used
      neutrophils, both resting and previously preactivated with TNF-alpha. The
      activity of C3 and C4 complement components and total antioxidant status were
      also measured. RESULTS: Showed that the chemiluminescence values were higher in
      patients with endometriosis than in comparative group. Preactivation of
      neutrophils with the use of TNF-alpha was significantly weakened. Both C3 and C4
      complement components revealed higher activity in women with endometriosis as
      compared to those without this disease. Total antioxidant status values were
      significantly lower in patients with endometriosis than in women from the
      comparative group. CONCLUSION: Innate immunity may play a significant role in the
      pathogenesis of endometriosis due to changes in its components activity that are
      observed in the course of this disease.

PMID- 14674154
TI  - [Serum concentration of leptin and resistin in girls during puberty].
AB  - The aim of this study was to find the link, if any between leptin, resistin and
      amount of adipose tissue in girls during puberty. MATERIAL AND METHODS: Forty six
      healthy girls aged 9, 8-15, 4 took part in this study, from which 12 were after
      menarche. Height, weight, body mass index, arm circumference and thickness of
      skin-fold were assessed. Serum concentrations of estradiol, FSH, LH, insulin,
      leptin and resistin were estimated. RESULTS: As it was expected, girls before
      menarche were younger, smaller, lighter, had smaller BMI, arm circumference and
      serum concentration of sex hormones than those after menarche. No significant
      differences between skinfold thickness on abdomen and at triceps site as well as
      between serum leptin (4, 88 +/- 4, 16 ng/ml in girls before menarche, 6.56 +/-
      5.15 ng/ml), were found. The concentrations of insulin occurred to be similar,
      too. No correlations between serum resistin and insulin concentration as well as
      between serum resitin and leptin concentration were noticed, either. The
      existence of high positive correlations between leptin concentration and skin
      fold thickness was confirmed but the correlation between resistin concentration
      and skinfold thickness was not proved. Interdependences between the serum
      concentrations of leptin, resistin and sex hormones were not found, either.

PMID- 14674155
TI  - [Reactive oxygen species as an inducing factor of neoplasms of female
      reproductive organs ].
AB  - AIM: In our study we measured selenium concentration in the blood of women with
      diagnosed cancer and benign tumors. The results were compared with healthy women.
      Some other parameters of the antioxidant system in all studied groups were also
      investigated, namely, activity of glutatione peroxidase, superoxide dismutase, as
      well as the levels of glutathione and malondialdehyde. MATERIAL AND METHODS: All
      parameters were determined in peripheral blood of (a) 47 women with diagnosed
      cancer (b) 46 women with diagnosed benign tumors, and (c) 20 healthy women
      (control group). Statistical analysis of the results was performed using
      "Statistica" software. RESULTS: Our results showed lower selenium concentration
      in the whole blood and plasma of cancer and benign tumor patients as compared to
      healthy women. An activity of glutathione peroxidase in erythrocytes and plasma
      were also lower in both patients' groups than in the control group. Statistical
      analysis of data revealed a positive correlation between selenium concentration
      and glutathione peroxidase activity in plasma. Lower activity of superoxide
      dismutase and increased concentration of malondialdehyde was noted in plasma of
      cancer patients as compared to healthy women. CONCLUSIONS: 1. A status of
      antioxidant systems plays an important role in carcinogenesis. 2. The antioxidant
      system of the women suffering from cancer is deficient. 3. A capacity of that
      system depends greatly on the concentration of antioxidants and activity of
      antioxidant enzymes, among them glutathione peroxidase.

PMID- 14674156
TI  - [Quality of life after mid-urethra polypropylene tape sling surgery (IVS, TVT) in
      female stress urinary incontinence].
AB  - INTRODUCTION: Urinary incontinence exerts a huge influence on women's quality of
      life in regard to hygienic problems. The great progress in female stress urinary
      incontinence (SUI) surgery was introduction of mid-urethra polypropylene sling
      procedures, which are characterized by very high efficacy, safety and minimal
      invasiveness. The aim of our study was to assess if functioning of lower urinary
      tract after minimum 1 year from TVT or IVS procedure has an impact on women's
      quality of life. MATERIALS AND METHODS: Analysis was done by means of King's
      quality of life questionnaire in Polish version from 1993. One hundred and sixty
      patients operated because of SUI in II-nd Department of Gynecology in Lublin in
      years: 1999-2001 were assessed. The mean time relapsed from surgery was 19 +/- 6
      months. Eighty women were operated by TVT method (monofilament tape) and eighty
      by IVS method (multifilament tape. Statistical analysis was done by means of
      STATISTICA program, version 6. To estimate patient's quality of life according to
      King's questionnaire the mode value (Mo) and the frequency of mode value (fr Mo)
      were used in respective questions. The results in both groups were compared by
      Mann-Whitney test. RESULTS: Most of patients assessed the general health
      condition as good (fr Mo = 25; 36.9%). In TVT group Mo value indicated good
      health condition (fr Mo = 30; 37.5%), whereas in IVS group general health
      condition was estimated most commonly as satisfactory (fr Mo = 33; 41.25%). In
      respect to incontinence impact on life in TVT group 37.5% of patients (fr Mo =
      30) reported some influence, while in IVS group 50% of women (fr Mo = 40)
      reported no influence (p = 0.16). Moreover, analysis revealed that in both groups
      the functioning of lower urinary tract does not influence their normal
      functioning, social contacts, physical activity, personal life, emotions or
      sleep. CONCLUSION: After modern incontinence surgery (TVT, IVS methods) the
      majority of patients reported that current bladder symptoms have no negative
      impact on their quality of life.

PMID- 14674157
TI  - [Tumor necrosis factor alpha and interferon gamma levels in peritoneal fluid of
      infertile women].
AB  - Changes in the peritoneal fluid environment have been implicated in the
      pathogenesis of endometriosis as well as in the decrease of fertility. Tumor
      necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) play a
      critical role in the generation of the immune response, leading to the enhanced
      proinflammatory cytokines and free radicals production. MATERIALS AND METHODS: 59
      women were studied, including 24 patients with unexplained infertility, 10
      infertile women with endometriosis (Io or IIo rAFS), 11 patients with PCOS and 14
      patients with tubal occlusion. TNF alpha and IFN gamma concentrations were
      measured in the PF using commercially available ELISA kits. RESULTS: Peritoneal
      fluid IFN gamma concentrations did not differ significantly between the studied
      groups. TNF alpha levels were significantly (p = 0.02) higher in the PF of
      endometriotic patients compared to women with tubal infertility. The positive
      correlation (R = 0.83; p < 0.01) has been found between TNF alpha and IFN gamma
      levels. CONCLUSIONS: Increased PF TNF alpha levels observed in patients with
      endometriosis may play a role in activation of peritoneal macrophages. Positive
      correlation between TNF alpha and IFN gamma suggests their synergistic
      stimulatory effect on the immunocompetent PF cells.

PMID- 14674158
TI  - [Changes in bone density in hemodialysed women treated with transdermal hormone
      replacement therapy].
AB  - OBJECTIVES: Renal insufficiency in women can cause menstrual disturbances and
      changes of hormonal profile leading to the decrease of bone mass density. Drug
      administration during dialysis also influences the bone density and increases the
      risk of osteoporosis. The aim of the study is to assess the effect of transdermal
      hormonal replacement therapy (HRT) in hemodialysed patients with secondary
      amenorrhea on bone density. MATERIAL AND METHODS: 10 women aged from 22 to 45
      years old were enrolled in the study. They received 17 beta-estradiol and
      norethisterone acetate in patches during 12 cycles. Densitometer of lumbar spine
      and serum estradiol concentration were measured before and after 12 cycles of
      therapy. RESULTS: The recurrence of regular vaginal bleeding, the increase of
      estradiol levels and bone mass density rate about 6% were observed. CONCLUSIONS:
      Transdermal hormonal replacement therapy in hemodialysed women with secondary
      amenorrhea revealed the efficacy of the treatment and prevention from
      osteoporosis.

PMID- 14674159
TI  - [Influence of a new monophasic oral contraceptive on body metabolism].
AB  - OBJECTIVES: Androgenic activity as adverse effects of oral contraception can
      influence on discontinuation of the therapy. New gestagens used in oral
      contraception do not reveal androgenic activity. The aim of the study is to
      assess the safety of the therapy with a new monophasic oral contraception on
      metabolism. MATERIAL AND METHODS: 99 healthy women aged mean 23.5 +/- 2.1 years
      were enrolled in the study. They received a monophasic contraceptive pill
      containing 30 micrograms ethinylestradiol and 2.0 mg dienogest during 13 cycles.
      Biochemical parameters in blood were measured before and after 6 and 12 cycles of
      therapy. RESULTS: The concentrations of liver enzymes, glucose and lipids did not
      differ significantly. CONCLUSIONS: The study suggests that a new monophasic oral
      contraceptive pill containing 30 micrograms ethinylestradiol and 2.0 mg dienogest
      is safe and good tolerated preparation.

PMID- 14674160
TI  - [Tissue reaction to polypropylene mono-or multi-filament tapes used in surgical
      techniques of stress urinary incontinence treatment].
AB  - OBJECTIVES: The "gold standard" in surgical treatment of stress urinary
      incontinence (SUI) is sling operation with polypropylene tape appliance under the
      mid urethra. There are two types of polypropylene tape which are the most popular
      nowadays. These two tapes are differently knitted so they have different
      biomechanical features. The TVT tape is monofilament, rarely knitted and highly
      elastic but the IVS mesh is multifilament, densly knitted and has only little
      possibility to stretch. The aim of our study was to assess the tissue reaction to
      the mono-(TVT) and multifilament (IVS) tapes. MATERIAL AND METHODS: The 10 mm x
      10 mm pieces of TVT and IVS tapes were implanted inlay the fascia of musculus
      abdominis rectus of 14 rat females (2 groups of 7 animals). The tapes with the
      margin of surrounding fascia were taken off after 6 weeks of healing. All samples
      were fixed in 10% Formaldehyde in phosphate buffered saline and embedded in
      paraffin. Four micron tissue sections were stained with hematoxylin and eosin,
      the reticulin silver impregnation stain according to Gomori (for collagen type
      III) and periodic acid Schiff and alcian blue (for proteoglycan). RESULTS: In all
      sections filaments visible as elipsoids were surrounded by resorptive granulation
      with large multinucleated giant cells like around "foreign body". The diameter of
      monofilaments was about 150 microns. The connective tissue in the vicinity of
      mesh was rich of inflammatory cells like histiocytes, lymphocytes, a few
      polymorphonuclear leucocytes as well as adipocytes and fibroblasts. The large
      multinucleated giant cells adjacent to monofilaments were relatively bigger than
      these cells around multifilaments. Moreover, this granulation tissue has a lot of
      new blood vessels and collagenous fibrous tissue. The multifilaments were about
      40 microns in diameter. The inflammatory granulation infiltrated aggregates of
      multifilaments. This tissue had only few inflammatory cells in comparison to
      tissue around monofilaments. The large multinucleated giant cells apposed to the
      mesh were small and collagen created thicker, more compacted bundles. CONCLUSION:
      The multifilament polypropylene tape induces weaker inflammatory tissue reaction
      than monofilament mesh. The thicker and more compacted collagen bundles are
      created around multifilaments so the natural tensile strength of the surrounding
      tissue is probably higher.

PMID- 14674161
TI  - [Comparison of assessing the patency of the Fallopian tubes during laparoscopy
      and during hysterosalpingography on television in infertile women with
      endometriosis].
AB  - OBJECTIVES: Sterility become nowadays not only medical, but as well socio
      economic problem. One of its major causes is endometriosis. Recurrent adnexitis-
      one of the most common symptoms of endometriosis might be the cause of fallopian
      tubes occlusion. The hysterosalpingography (HSG) can be helpful to diagnose this
      tubal pathology. DESIGN: To compare the assessment of fallopian tubes patency
      during HSG with the results of laparoscopy in infertile women with endometriosis.
      MATERIAL AND METHODS: 331 women with endometriosis who were diagnosed during
      laparoscopy examination between 1998-2002 due to sterility. The presence of
      endometriosis was confirmed during laparoscopy. In each patient the control of
      the patency of both fallopian tubes was performed. These data were confirmed with
      those from HSG performed during follicular phase on the television path. The
      absence of the contrast passage through fallopian tubes as well as the only trace
      contrast passage into abdominal cavity were classified as tubal obstruction.
      RESULTS: In patients during the HSG physiological uterine shape and size in
      91.3%, the bicornis uterus in 6.6%, and the unicornis uterus in 2.1% were
      observed. During laparoscopy we diagnosed the physiological uterine shape and
      size in 88.8%, the bicornis uterus in 8.2%, and the unicornis uterus in 3.0%. The
      diagnostic compatibility of these both examinations was 90.6%. In HSG the correct
      anatomical course of both fallopian tubes without occlusions in 51.7%, the only
      unilateral patency in 36.7%, and bilateral occlusions in 11.6% were found. During
      laparoscopy we diagnosed the anatomical course of both fallopian tubes without
      occlusions in 36.7%, the only unilateral patency in 33.3%, and bilateral
      occlusions in 30.0%. The diagnostic compatibility of these both examinations was
      49.6% for both fallopian tubes, and 34.2% for the only one fallopian tube. In
      16.2% both results were incompatible. CONCLUSIONS: The incorrect contrast passage
      through the fallopian tubes and its increased pressure during HSG in women with
      the characteristic history and clinical symptoms can suggest endometriosis. In
      these cases laparoscopy is necessary as the additional examination in the
      diagnostics of fallopian tubes patency, but the only objective method in
      diagnosis of endometriosis.

PMID- 14674162
TI  - [Diagnosis of overactive bladder influenced by methods of clinical assessment-
      micturition diary vs. urodynamics].
AB  - INTRODUCTION: Most characteristic symptom of overactive bladder is urgent,
      possibly painful, desire to void. This complaint is caused by autonomous bladder
      contractions. The increased activity of detrusor muscle is not only responsible
      for the urgency but also is the direct reason for the development of urge urinary
      incontinence. THE AIM OF THE STUDY: The comparison of the subjective (micturition
      diary) and objective (urodynamic investigation) mode of diagnosis of overactive
      bladder. MATERIAL AND METHOD: Twenty one women complaining of symptoms of the
      overactive bladder were included into the study. The infection of lower urinary
      tract was ruled out based on the results of urinalysis. Each patient reported
      urinary symptoms (number of urgency episodes and urge urinary leakages) in
      micturition diary for seven days. Thereafter, all participants underwent the
      urodynamic investigation that included uroflowmetry and cystometry. RESULTS: Data
      obtained from micturition diaries proved that all patients had subjective
      symptoms of overactive bladder (n = 21). However, only 8 subjects met overactive
      bladder diagnostic criteria on urodynamic investigation. The data obtained from
      micturition diaries and urodynamics were compared between group with objectively
      (urodynamic investigation) and subjectively (micturition diary) diagnosed
      overactive bladder. CONCLUSIONS: 1. There is marked discrepancy between data
      obtained from micturition diary and the results of urodynamic investigation. 2.
      It was shown that the diagnosis of overactive bladder cannot be made solely on
      the basis of maturation diary. 3. Volume of voided urine measured at uroflowmetry
      and volume of infused fluid causing strong desire to void are best markers of
      urodynamically proven diagnosis of overactive bladder.

PMID- 14674163
TI  - [Relationship between climacteric symptoms and serum neuropeptide Y level in
      postmenopausal women].
AB  - The aim of this study was to determine circulating levels of neuropeptide Y (NPY)
      in postmenopausal women with climacteric symptoms in comparison with regularly
      menstruating women in reproductive age and to assess the relationship between
      serum NPY levels and the presence of climacteric symptoms in postmenopausal
      women. MATERIALS AND METHODS: We studied 41 postmenopausal patients attending the
      Clinic of Gynecological Endocrinology, University of Medical Sciences, Poznan
      because of climacteric complaints. The controls were 20 regularly menstruating
      women in reproductive age. In the study group the severity of climacteric
      symptoms was assessed using the Kupperman index. Serum 17 beta-estradiol,
      follicle stimulating hormone (FSH) and NPY concentrations were measured by
      radioimmunoassay in both groups. RESULTS: The mean value of the Kupperman index
      in the study group was 23.4 points (SD +/- 10.4 points); 17 beta-estradiol serum
      concentration was lower than 0.014 ng/ml in 30 women from the study group and the
      mean serum estradiol level for the remaining group was 0.023 ng/ml (SD +/- 0.03
      ng/ml); the mean serum FSH concentration in the study group was 98.2 Ul/l (SD +/-
      11.8 IU/l), the mean serum NPY concentration in the study group was 18.4 ng/ml
      (SD +/- 8.3 ng/ml). The mean serum NPY concentration in the control group was
      12.9 ng/ml (SD +/- 6.3 ng/ml) and was lower than in the study group (t-test: p <
      0.05). The difference between serum NPY concentration in patients with a
      particular climacteric symptom and patients without was not statistically
      significant for any symptom (t-test: p > 0.05). CONCLUSION: Serum NPY level is
      higher in postmenopausal women than regularly menstruating women in reproductive
      age an may be responsible for climacteric symptoms presence.

PMID- 14674164
TI  - Insuring America's health. American Association of Health Plans and Health
      Insurance Association of America unify.

PMID- 14674165
TI  - Prime ministry of women's health.

PMID- 14674167
TI  - A new generation of wellness programs.

PMID- 14674168
TI  - Nurse call centers extend their reach.

PMID- 14674166
TI  - Assessing needs and outcomes, health plans improve mental health care.

PMID- 14674169
TI  - Improving medication safety.

PMID- 14674170
TI  - Attracting and retaining participants: a checklist.

PMID- 14674172
TI  - Automating complex work: the next big step in IT.

PMID- 14674171
TI  - Changing the face of medical policy.

PMID- 14674173
TI  - Canadian cardiovascular hospitalization rates and length of stay.

PMID- 14674174
TI  - Defining the new normal.
AB  - Throughout the extended SARS outbreak, healthcare organizations across Ontario
      operated under directives that imposed significant changes to patient and
      operational practices. The outbreak dramatically illustrated the critical need to
      transform healthcare organizations to a "new normal" state of operation to
      respond to the ease by which contagious diseases can spread globally.

PMID- 14674175
TI  - Restrictive visitor policies: feedback from healthcare workers, patients and
      families.
AB  - With the hospital-based transmission of Severe Acute Respiratory Syndrome (SARS)
      in Ontario, acute care hospitals severely restricted visitor access. Now that the
      SARS outbreak is under control, hospitals struggle with the balance between
      adhering to patient- and family-centred care models, and addressing the future
      threat of infectious diseases. To evaluate the effect of visitor restrictions and
      to guide future visitation policies, the Ottawa Hospital conducted a preliminary
      survey of patients, next of kin, staff, physicians and volunteers. Ninety percent
      of staff surveyed supported some form of visitor restrictions, while 71%
      indicated that they felt comfortable asking visitors to leave if they had
      exceeded current restrictions. The majority of patients (80%) and next of kin
      (76%) were at least moderately satisfied with current restricted limiting hours.
      A disproportionate number of positive comments on current visiting restrictions
      were received from both patients and staff. In the absence of evidence on which
      to base future visitor policy development, objective input from healthcare
      workers, patients and families is invaluable.

PMID- 14674176
TI  - SARS and ethics.
AB  - SARS is a devastating disease that caused widespread morbidity and mortality, as
      well as tremendous fear and uncertainty across the global village. There are
      numerous challenging medical aspects of this disease. Methods required to control
      it also raised significant ethical challenges for decision-markers both in real
      time, and for the future. A group at the Joint Centre for Bioethics (JCB) at the
      University of Toronto formally explored the ethical dimensions of this outbreak.
      The author briefly reviews the analysis by the JCB group and further examines how
      bioethical principles and theories relate to the numerous ethical issues raised
      by SARS and the methods used in its containment.

PMID- 14674177
TI  - Life at the epicentre: my first year at North York General Hospital.
AB  - My inaugural year at NYGH neatly bisects, with the two halves marked by decidedly
      different challenges. The first six months brought its share of difficulties, and
      with it some tests of will on my part. But it all paled in comparison with what
      followed, as we coped with the outbreak of SARS.

PMID- 14674178
TI  - The Saskatchewan Surgical Care Network--toward timely and appropriate access.
AB  - Earlier this year, a paper in Hospital Quarterly, "Creating a Surgical Wait List
      Management Strategy for Saskatchewan," described the development of a surgical
      wait list strategy for Saskatchewan. The initial strategy development process
      uncovered several issues that needed to be addressed including lack of data,
      inconsistent priorities and frustration on the parts of both providers and
      patients. This second paper outlines the key points of the recommended surgical
      wait list strategy and the work to date in its implementation.

PMID- 14674179
TI  - Medical imaging in Canada: bringing the picture into focus.
AB  - Until now, we have had little systematic knowledge of the medical imaging
      landscape in Canada. An overview of recent trends and emerging issues is
      essential to sound decision-making at all levels.

PMID- 14674180
TI  - Safe: a status update on information security and the hospital community.
AB  - IT Security and Privacy are becoming increasingly visible "hot topics" across the
      full spectrum of industry and service sectors. Legislation and global "best
      practices" are working hard to defend organizations and individuals against
      escalating, rapidly evolving cyber-threats. Predictably, the threat landscape is
      having an impact on all levels to varying degrees: governmental, organizational
      and individual. This article introduces the basic context for information
      security and offers insight into how a number of hospitals are addressing the
      situation, what barriers they currently face and what opportunities they see
      unfolding.

PMID- 14674181
TI  - Taking the next step to privacy compliance for hospitals: implementing the OHA
      guidelines.
AB  - The recently released "Guidelines for Managing Privacy, Data Protection and
      Security for Ontario Hospitals," prepared by the Ontario Hospital eHealth Council
      Privacy and Security Working Group (the "Guidelines") are useful in that they
      provide a comprehensive overview of the types of issues raised for hospitals by
      existing and pending privacy legislation, and a very high-level framework for
      addressing same. However, the Guidelines are, as stated high-level guidelines
      only,--leaving hospital management to grapple with the next big step towards
      privacy compliance: how to operationalize the Guidelines within their particular
      hospital.

PMID- 14674182
TI  - The expanded Chronic Care Model: an integration of concepts and strategies from
      population health promotion and the Chronic Care Model.
AB  - Given the increasing incidence of chronic diseases across the world, the search
      for more effective strategies to prevent and manage them is essential. The use of
      the Chronic Care Model (CCM) has assisted healthcare teams to demonstrate
      effective, relevant solutions to this growing challenge. However, the current CCM
      is geared to clinically oriented systems, and is difficult to use for prevention
      and health promotion practitioners. To better integrate aspects of prevention and
      health promotion into the CCM, an enhanced version called the Expanded Chronic
      Care Model is introduced. This new model includes elements of the population
      health promotion field so that broadly based prevention efforts, recognition of
      the social determinants of health, and enhanced community participation can also
      be part of the work of health system teams as they work with chronic disease
      issues.

PMID- 14674183
TI  - Branding down to the core: branding not-for-profits.
AB  - Many not-for-profits do not view their organization as a brand. After all, the
      reason for being lies in the purpose. Branding is something corporate businesses
      do to justify their existence. But what is an organization's purpose? And what if
      everyone in the organization does not agree on that purpose over time or across
      departments? How can an organization formalize a strategy if it isn't sure what
      the mission is?

PMID- 14674184
TI  - Helping the world to hear. William F. Austin.

PMID- 14674185
TI  - Spirit-inspired worldwide humanitarian. Gloria Johnson-Rodgers.

PMID- 14674186
TI  - Social advocates and 'new breed' philanthropists. Steven & Michele Kirsch.

PMID- 14674187
TI  - Personification of service in action. Vice-admiral Willam P. Lawrence.

PMID- 14674188
TI  - A visionary who uses leverage to make a difference. Jerry Lee.

PMID- 14674189
TI  - Hero, coach, teacher & mentor. Tom Osborne.

PMID- 14674190
TI  - One who loves children. Betty Tisdale.

PMID- 14674191
TI  - Amazing Anthony. Giving hats and love to cancer patients.

PMID- 14674192
TI  - Queenly Kayt + magnificent Maggie: taking caring and community service to a high
      art.

PMID- 14674193
TI  - Gandhiam Gregory. Bringing genius and passion to world peace.

PMID- 14674194
TI  - Marvelous Makenzie. Giving foster kids the gift of duffel bags an dignity.

PMID- 14674195
TI  - Johnson & Johnson. Named 2003 most caring corporation in America.
AB  - In summary, there are bountiful reasons to justify the selection of J&J as the
      most caring corporation in America. The examples provided herein are merely
      illustrative but not exhaustive. J&J and its more than 100,000 employees around
      the world are clearly living out their credo, which calls for them to be good
      citizens and to support good works and worthy charitable activities. Along the
      way they've helped millions of people. They have established a culture of caring
      and proven conclusively for the corporate world, that you can do well by doing
      good. J&J deserves the respect and commendation of good people everywhere. They
      have set the standard against which all corporations will be judged in the
      future.

PMID- 14674196
TI  - A tribute to Dr. William A. Haseltine. Interview by Val J. Halamandaris.

PMID- 14674197
TI  - Sharps disposal containers.

PMID- 14674198
TI  - Seroprevalence of hepatitis C virus infection among indigent urban pregnant women
      in Zimbabwe.
AB  - OBJECTIVE: To estimate the seroprevalence of hepatitis C virus (HCV) infection
      among indigent pregnant women. DESIGN: A serological survey study of indigent
      pregnant women admitted for labour and delivery. SETTING: Harare Maternity
      Hospital, Harare, Zimbabwe. SUBJECTS: A random sample of 1,607 women, delivering
      at the hospital during the study period agreed to participate in the research.
      Serum samples were available for 1,591 women. MAIN OUTCOME MEASURES: Serum
      samples were tested for the presence of antibodies to HCV using a second
      generation agglutination assay and a third generation enzyme immuno-assay (EIA).
      RESULTS: Of the 1,591 women tested 25 (1.6%) were anti-HCV positive (95%
      confidence interval 1.0% to 2.2%). The frequency of anti-HCV positives was
      associated with maternal age (p = 0.0202) and maternal syphilis status (p =
      0.020). Gravidas aged 25 to 29 years had the highest anti-HCV seroprevalence
      (3.4%) as compared with gravidas of other age categories (1.0% to 1.5%). Women
      with serologic evidence of syphilis infection during the index pregnancy had an
      increased prevalence of anti-HCV as compared with those women without evidence of
      syphilis infection (7.9% versus 1.4%, p = 0.020). There was some evidence (p =
      0.094) that a positive prior history of delivering a stillborn infant was also
      associated with an increased prevalence of anti-HCV (4.1% vs 1.4%). Other
      maternal characteristics, including hepatitis B virus carriage status, parity,
      and whether she had received prenatal care during the index pregnancy were not
      determinants of maternal anti-HCV status. CONCLUSIONS: Overall, hepatitis C
      antibody was detected in 1.6% of indigent women delivering at Harare Maternity
      Hospital. This proportion of anti-HCV positive pregnant women is similar to
      estimates published for North American and European women. Factors positively
      associated with maternal seropositivity in our population included maternal age
      (between 25 to 29 years), prior history of delivering a stillborn infant, and
      seropositivity for syphilis during the index pregnancy. Given the relatively low
      seroprevalence of HCV and the fact that risk factors for HCV infection remain
      largely unknown, more studies are needed to identify high risk populations likely
      to benefit from HCV screening and treatment programmes.

PMID- 14674199
TI  - Association of HIV infection with the development of severe and complicated
      malaria cases at a rural hospital in Zimbabwe.
AB  - OBJECTIVE: To determine the association between HIV infection and progression of
      Plasmodium falciparum malaria illness in Hurungwe district, Zimbabwe. DESIGN:
      Prospective cohort. SETTING: Hurungwe Rural Hospital in Mashonaland West
      Province, Zimbabwe. SUBJECTS: Blood slide positive P. falciparum malaria
      patients. MAIN OUTCOME MEASURES: Development of severe and complicated malaria.
      RESULTS: A total of 659 clinical malaria cases were investigated and 237 (36.0%)
      confirmed cases entered the study. The total HIV positive malaria patients were
      82 (34.6%) of confirmed cases or 12.4% of the total clinical cases. The case
      fatality rate was 5.9% (14 deaths) in the confirmed cases and 11 of these deaths
      were HIV positive. The commonly reported complications were high parasite count
      of 2% or more (38.5%), anaemia (29.0%), cerebral malaria (23.1%), low blood
      pressure (8.3%) and renal failure (1.2%). The HIV positive cases which developed
      severe and complicated malaria were 72, 30.4% of the sample studied or 55.8% of
      the total severe and complicated cases. The mode of transport to the nearest
      health centre was the only confounding factor identified during the analysis.
      After adjusting for this confounding factor, the risk of developing severe and
      complicated malaria was 2.35 (95% CI 1.85 to 2.98) times more in the HIV positive
      malaria patients than in HIV negative patients. CONCLUSION: We conclude that HIV
      infection is significantly associated with the development of severe and
      complicated malaria. There is need for future studies to determine whether HIV
      positive malaria patients require different management protocol from HIV negative
      malaria patients.

PMID- 14674200
TI  - Pharmacological actions of Heteromorpha trifoliata ("dombwe") on rat isolated
      muscle preparations.
AB  - OBJECTIVE: To investigate the effects of Heteromorpha trifoliata on rat uterine
      and skeletal muscle. DESIGN: Laboratory based study using experimental animals.
      Investigating the effects of the plant extract and agonists on isolated muscle
      preparations. SETTING: Department of Physiology, University of Zimbabwe.
      SUBJECTS: 28 Sprague-Dawley rats. MAIN OUTCOME MEASURES: Amplitude of contraction
      of uterine smooth muscle and skeletal muscle. RESULTS: Experiments were performed
      on the isolated rat uterus preparation in which strips of myometrium were placed
      in tissue baths filled with Kreb's solution. The aqueous extract of the root bark
      of Heteromorpha trifoliata ("dombwe") contracted the rat uterus. The contractions
      were not antagonised by atropine but were blocked by both cyproheptadine and
      verapamil. In addition, "dombwe" induced a contracture of the rat diaphragm
      muscle in the presence of alcuronium. CONCLUSIONS: The contractile effects on the
      uterus appear to involve stimulation of 5-HT2 receptors leading to an increase in
      calcium influx into the smooth muscle cell. Promotion of calcium influx could
      also explain the effects observed on the skeletal muscle preparation since the
      contracture induced by "dombwe" occurred in the presence of the nicotinic
      antagonist, alcuronium. In view of the effects of "dombwe" on other smooth muscle
      preparations (from previous work) it appears that the pharmacological profile of
      the crude aqueous extract of the root bark of Heteromorpha trifoliata is complex
      and suggestive of the presence of more than one active ingredient.

PMID- 14674201
TI  - Pathological study of retinoblastoma in Mbarara, Uganda.
AB  - OBJECTIVE: Histological study of retinoblastoma: cellular differentiation, optic
      nerve and choroidal involvement. DESIGN: Series of specimens examined in the
      Pathology laboratory. SETTING: Department of Pathology, Mbarara University
      Teaching Hospital (MUTH) and Ruharo Eye Centre, Mbarara. SUBJECTS: 32 eye
      specimens. RESULTS: 31 specimens consisted of poorly differentiated tumours and
      one specimen had a well differentiated retinoblastoma showing Flexner
      Wintersteiner rosettes. Fifteen out of 25 specimens with optic nerves showed both
      choroid and optic nerve invasion. In 10 eye specimens, the optic nerves and
      choroid were free of tumour. In the remaining seven specimens, the optic nerves
      were not submitted with the enucleated specimens and there was no choroidal
      involvement on histology. CONCLUSION: This review supports findings from previous
      studies done in Africa which indicated that poorly differentiated retinoblastoma
      is more common among African children than well differentiated retinoblastoma.

PMID- 14674202
TI  - Abnormal rotation of the right kidney.
AB  - An unusual case of abnormal rotation of the right kidney with extra renal calyces
      and pelvis is reported in a Caucasian female. The hilum of this kidney is
      directed posteriorly. The condition did not appear to be associated with any
      pathology. This case is discussed in the light of the its embryological
      development.

PMID- 14674203
TI  - Former migrant mineworkers with respiratory disease: the South African
      compensation system, and implications for neighbouring countries.
AB  - In the region of Southern Africa, substantial numbers of people, primarily males,
      have been employed in the South African mining industry. Migrant workers from
      neighbouring countries have constituted a large part of the work force. Until
      recently, there has been little or no attention directed toward the state of
      health of these individuals, despite the fact that their work involves a high
      health risk, especially in regard to mine-related lung diseases. In addition, the
      South African workers' compensation programme has seldom been utilised by the
      migrant worker who is a victim of occupational disease. However, recent
      experiences from Botswana show that compensation claims can be successfully made
      from the neighbouring countries where the migrant workers originate. Efforts are
      being made to address the problem systematically, and the government of Botswana
      is actively involved. The major occupational lung disorders are described
      briefly, and differential diagnostic problems with pulmonary TB are discussed.
      Furthermore, a survey of the compensation system in South Africa is presented,
      and practical steps for medical examinations involving compensation claims are
      described.

PMID- 14674204
TI  - An overview of spontaneous reporting of adverse drug reactions (ARDs) in
      Zimbabwe.

PMID- 14674205
TI  - Effects of the Zimbabwe Defence Forces training programme on body composition and
      reproductive hormones in male army recruits.
AB  - OBJECTIVES: To investigate the effects of a four month endurance training
      programme on body composition and reproductive hormone levels. DESIGN: PRE and
      POST training comparative study. SETTING: Zimbabwe Military Academy, Gweru,
      Zimbabwe. SUBJECTS: 77 male recruit volunteers participating in the Zimbabwe
      Defence Forces cadet training programme. MAIN OUTCOME MEASURES: Percent body fat,
      fat free mass, body mass index, total serum testosterone, luteinising hormone
      (LH) and follicle stimulating hormone (FSH) compared using the paired t-test.
      RESULTS: There was a significant decrease in all parameters measured after four
      months of endurance training. Decreases in body composition parameters were 54%
      in percent body fat, 6% in fat free mass, and 13% in body mass index. There was a
      dramatic 58% drop in testosterone, 60% drop in LH and 15% drop in FSH after four
      months of endurance training. CONCLUSIONS: The Zimbabwe Defence Forces cadet
      training programme, an endurance training programme induces a state of negative
      energy balance in trainees. This results in a decrease in % body fat and body
      mass index due to utilisation of fat stores as a source of energy and a decrease
      in fat free mass due to gluconeogenic utilisation of muscle protein as energy
      source for muscle activity. There is impaired hypothalamic-pituitary-testicular
      axis function as evidenced by the state of hypogonadal-hypogonadism (low
      testosterone, LH and FSH). This may be attributed to: 1. gonadotrophin releasing
      hormone pattern generator malfunction due to the stress of intense physical
      activity and 2. withdrawal of energy expenditure from reproductive machinery as a
      way of conserving energy for more vital processes in the prevailing state of
      energy starvation.

PMID- 14674206
TI  - A community based study of HIV in women in rural Gutu District, Zimbabwe 1992 to
      1993.
AB  - OBJECTIVE: To estimate the prevalence of HIV-1 infection and its relation to
      socio-economic and obstetric history factors. DESIGN: A cross sectional study.
      SETTING: 12 randomly selected villages in rural Gutu District, Zimbabwe.
      SUBJECTS: All women of fertile age (15 to 44 years) in the selected villages were
      invited to participate. In total 1,213 women were interviewed and examined. On
      average 75% and 81% of those eligible in 1992 and 1993 respectively participated
      (range for villages 57 to 87%). MAIN OUTCOME MEASURES: HIV sero-positivity.
      RESULTS: HIV prevalence was high, 21.9%. Single women below 20 years had the
      lowest prevalence (7.6%), while the highest (30.0%) was found in married women
      aged 20 to 29 years. Using a case-referent approach, women divorced, widowed or
      separated had twice as high a risk of being HIV positive as single women (Odds
      Ratio (OR) = 2.03; 95% confidence interval (CI) 1.40 to 2.93). There was a huge
      difference in the prevalence of HIV between villages, from 8.4 to 32.8%, thus the
      risk of having HIV in the two villages with the highest prevalence was more than
      five times higher (OR = 5.21 and 5.31 respectively) than in the village with the
      lowest. The multivariate logistic regression confirmed the findings of an
      increased risk for women aged 20 to 39 years as compared with women 15 to 19
      years, and for women that were divorced, widowed or separated as compared with
      single. It also confirmed that the huge difference in the prevalence found
      between wards was statistically significant. CONCLUSION: Women contract HIV early
      in marriage. Young men's risk behaviour needs to be addressed and women must be
      aware of their risks before marriage.

PMID- 14674207
TI  - Is antenatal antibody screening worthwhile in the Zimbabwean population?
AB  - OBJECTIVES: To determine the incidence of clinically significant allo-antibodies
      in antenatal care (ANC) patients, and make recommendations on laboratory
      management of such cases in similar settings in Zimbabwe. DESIGN: A retrospective
      study. SETTING: Harare Central Hospital, a tertiary medical centre in Harare.
      SUBJECTS: Patients attending the ANC clinic at Harare Central Hospital. MAIN
      OUTCOME MEASURES: Blood group tests, allo-antibody screen, development of
      haemolytic disease of the newborn. RESULTS: 3,000 patients were grouped and
      screened and 96.7% were found to be Rhesus positive, 0.5% were Rhesus Du positive
      and 2.8% were Rhesus negative. An overall antibody incidence of 1.7% (n = 50) was
      obtained, 1.0% (n = 30) of which were strongly positive and 0.7% (n = 20) were so
      weakly positive so that no antibodies could be identified. Antibodies identified
      from those patients with strongly positive antibody screen were anti-D 13.3% (n =
      4), anti-E 6.7% (n = 2), anti-Jsb 3.2% (n = 1), anti-Lea 23.3% (n = 7) and anti
      Leb 20% (n = 6). Antibodies of unknown specificity were detected from 20% (n = 6)
      of the patients. Four (13.3%) of the specimens were insufficient for antibody
      identification. Clinical records of those patients with a strongly positive
      antibody screen were examined and anti-D and anti-Jsb were observed to have
      caused severe to fatal Haemolytic Disease of the Newborn (HDN). The four anti-D
      positive cases resulted in two still births and two jaundiced babies. The single
      anti-Jsb positive antibody case resulted in an intra-uterine death. Antibodies
      that are generally considered of no clinical significance did not cause HDN in
      this study. CONCLUSION: Anti-D remains the most important allo-antibody causing
      HDN, regardless of the availability of anti-D immunoglobulin for prophylaxis.
      Only Rhesus D negative women and those who have clinically significant antibodies
      need have repeat antibody screens during the rest of the pregnancy. In line with
      the current policy of screening all patients at booking, the policy on repeats is
      not clear and was not evident in this study.

PMID- 14674208
TI  - Osteosarcoma in Ga-Rankuwa Hospital: a 10 year experience in an African
      population.
AB  - OBJECTIVES: This is a clinicopathological correlation of cases of osteosarcoma
      diagnosed and treated at Ga-Rankuwa Teaching Hospital. DESIGN: A retrospective
      study. SETTINGS: Department of Orthopaedics and Anatomical Pathology at Ga
      Rankuwa/MEDUNSA Academic complex, a tertiary referral centre. SUBJECTS: 66
      patients with a diagnosis of osteosarcoma. MAIN OUTCOME MEASURES: Records of the
      bone tumour registry were reviewed and cases of osteosarcoma were identified.
      Slides were retrieved and the diagnoses confirmed in all the cases. Information
      pertaining to clinical presentation and patients' survival was obtained from the
      clinical records. RESULTS: The patients' ages ranged from nine years to 75 years
      with a mean of 19.7 years (median 17 years). Most cases occurred around the knee
      and the male to female ratio was 2.7:1. The five year survival rate was 7.5% and
      only 25.8% survived for one year. CONCLUSION: Our patients present with advanced
      disease leading to poor survival.

PMID- 14674209
TI  - Ileo-caecal tuberculosis mimicking colonic tumour--case report.
AB  - A case of ileocaecal tuberculosis simulating a colonic tumour is reported. A 43
      year old male patient presented with abdominal pain, weight loss, fever and right
      iliac fossa mass. Laboratory investigations and ultrasonography were not
      specific. Laparotomy with ileocaecal resection was carried out and
      histopathological examination confirmed the diagnosis of tuberculosis.

PMID- 14674210
TI  - Trends in cancer pain management.
AB  - BACKGROUND: Pain is a prevalent symptom in cancer patients, affecting up to 50%
      of patients undergoing active cancer treatment and up to 90% of those with
      advanced disease. Although adequate relief can be achieved in the majority of
      cancer patients, pain is often treated inadequately in traditional settings and
      sometimes even under the management of more specialised units. In this review the
      authors use their experience and that of others to review the evaluation and
      diagnosis of pain syndromes and the principles of management. This is in keeping
      with increasing recognition by bodies such as the World Health Organisation and
      other governmental agencies who have recognised the importance of pain management
      as part of routine cancer care. Conducting a comprehensive assessment,
      competently providing analgesic drugs, and communicating with the patient and
      family allow effective management of pain in the cancer patient.

PMID- 14674211
TI  - Drug use indicators at St Mary's Clinic.

PMID- 14674212
TI  - Aids is now the commonest clinical condition associated with multilineage blood
      cytopenia in a central referral hospital in Zimbabwe.
AB  - OBJECTIVE: To describe the clinical features and diagnosis of patients
      hospitalised and found to have multilineage peripheral blood cytopenias. DESIGN:
      Prospective cross sectional study. SETTING: Parirenyatwa Hospital, a central
      referral hospital in Harare, Zimbabwe. SUBJECTS: 231 consecutive patients whose
      blood parameters revealed bi- or trilinneage cytopenia during a five month period
      in 1996. MAIN OUTCOME MEASURES: 1. Blood cytopenia was described as: (a)
      Haemoglobin concentration = or < 100 g/L (b) Total leucocyte count = or < 3.5 x
      10(9)/L (c) Platelet count = or < 100 x 10(9)/L 2. Other clinical and diagnostic
      features. RESULTS: The highest percentage of multilineage blood cytopenia was in
      the age bracket 30 to 44 years and the male to female ratio was 1.4:1.
      Pancytopenia was found in 32.5% of patients, while bilineage cytopenia occurred
      in 67.5%. The commonest bilineage pattern was the combination of anaemia and
      thrombocytopenia occurring in 46.3% of all study cases or 68.5% of bilineage
      cytopenias. Anaemia was the most frequent cytopenia; it was found in 95.2% of all
      study cases. CONCLUSION: The commonest condition with which multilineage blood
      cytopenia was associated was AIDS which was diagnosed in 25.1% of the study
      cases.

PMID- 14674213
TI  - Chlamydia trachomatis in symptomatic and asymptomatic men: detection in urine by
      enzyme immunoassay.
AB  - BACKGROUND: Infection with Chlamydia trachomatis is known to be a common cause of
      urethritis and cervicitis. The standard methods of detection require the
      collection of intra-urethral and/or cervical swabs, which may be submitted for
      culture, antigen detection or nucleic acid amplification. The collection of swabs
      is suitable only within the context of a health care facility. Recent reports
      have indicated that antigen detection can be used with urine specimens, and
      because these can be self-collected, this may be particularly useful for the
      detection of asymptomatic carriage. OBJECTIVE: To determine the sensitivity and
      specificity of urine antigen assays in the detection of chlamydial infection in
      men. SETTING: Two groups of men were investigated; men with urethritis attending
      clinics or private practitioners, and healthy adult men enrolled into either
      urban or rural HIV prevention projects. METHODS: Urine samples from men in both
      groups were collected and assayed for the presence of chlamydial antigen using a
      commercial enzyme immunoassay (EIA) kit. For symptomatic men an intra-urethral
      swab was also collected and assayed for antigen detection using a commercial EIA.
      For asymptomatic men, a ligase chain reaction was carried out on the same urine
      sample. RESULTS: The prevalence of chlamydial antigen in symptomatic men was 15%
      (39/257), and in asymptomatic men was 4% (15/349). The sensitivity and
      specificity of urine EIA for symptomatic men was 87% and 83% respectively. For
      asymptomatic men, the sensitivity of urine EIA was 86%, and the specificity was
      100%. CONCLUSION: Urine EIA is a relatively inexpensive method for the detection
      of chlamydial infections in men. The true specificity in symptomatic men may be
      higher, as the "gold standard" that we used may give false negative results.
      Antigen EIA for examination of urine specimens from community surveys of
      asymptomatic men may be particularly useful because of the low cost of assays,
      and because urine samples can be self-collected without discomfort to study
      subjects. The prevalence of C. trachomatis that we describe here is consistent
      with other studies of chlamydial epidemiology in Zimbabwe.

PMID- 14674214
TI  - Nephroblastoma (Wilms' tumour) diagnosed in the Department of Anatomical
      Pathology Medunsa/Ga-Rankuwa Hospital for the period 1980 to 1997.
AB  - OBJECTIVE: The aim of the analysis was to describe the clinicopathological
      features of Wilms' Tumour (WT) diagnosed in our Department and compare results to
      other WT Registers. DESIGN: All cases of WT for the period 1980 to 1997 were
      retrieved from the Register of Renal Tumours of Childhood. SETTING: The Medical
      University of Southern Africa, Department of Anatomical Pathology and Department
      of Paediatrics, Ga-Rankuwa Hospital. SUBJECTS: A total of 171 cases of WT (97% of
      all renal tumours) were the subject of the analysis. RESULTS: The age of the
      patients ranged from four to 216 months. The two sexes were represented equally.
      Tumours were solid in 73.9%, cystic in 20% and mixed in 6.1%. There were as many
      tumours involving the right kidney as those involving the left kidney. In nine
      cases WT was bilateral. Only 2.4% of tumours were in stage I and II. The mass of
      the kidney with tumour ranged from 50 g to 5,400 g and in diameter from three to
      28 cm. Histopathologically classic, blastemal and stromal type were nearly
      equally represented. Follow up was very inadequate and in 66% of cases the fate
      of the patient remains unknown. CONCLUSION: Occurrence of WT is similar to that
      reported from other regions of the world. Cases are in a more advanced stage than
      reported by SIOP and NWTS. Follow up is highly inadequate.

PMID- 14674215
TI  - Understanding medical ethics.
AB  - Moral thinking is embedded within cultures, and we use ethics all the time in our
      dealings with one another. Many functioning communities tend to share some values
      that reflect a particular view of the importance of human life in quantity and
      quality. Rights and duties form an interconnected network of obligations that
      protect the security of individuals and groups. In health care, the motives and
      virtues of practitioners are important sources of the determination to provide
      care for the ill within the limits of resource constraints. Ethics and the law
      have similarities, but also significant differences that may cause tension
      between the two systems. Health care is morally grounded, and provides a bulwark
      against the widespread fear of disease and suffering. The way in which health
      care is delivered depends on both national wealth and community values. Ethical
      problems can be seen as dilemmas, in which there are conflicting values. Modern
      ethical thinking in health is complicated by the need to consider the values and
      interests of many stakeholders--patients, health care workers, families,
      politicians, administrators, health bureaucrats and many others. There are ways
      of ethical thinking that take account of these often countervailing interests. No
      universally 'right' answers can be specified. The mode and the thoroughness of
      ethical consideration, and the careful consideration of local community values,
      will help to assure that we make the best possible decisions for the time and
      place.

PMID- 14674216
TI  - What are ethics (more particularly medical ethics)?

PMID- 14674217
TI  - Teaching medical ethics.

PMID- 14674218
TI  - Screening for cervical cancer, a priority in Zimbabwe?
AB  - In several (first world) countries many cases of cancer of the cervix are
      prevented through regular screening of women at risk by means of a Pap (anicolao)
      smear. The adage "prevention is better than cure" suggests that mass screening
      should also take place in Zimbabwe. A critical public health viewpoint is
      presented which discusses the complexity of a national cervical cancer screening
      programme.

PMID- 14674219
TI  - Your diagnosis. A boy with hepatomegaly, muscle hypertrophy and absence of
      adipose tissue.

PMID- 14674220
TI  - Clinical management of acute respiratory distress syndrome in pediatrics.

PMID- 14674221
TI  - Adult respiratory distress syndrome (ARDS) is not a disease limited to adults.

PMID- 14674222
TI  - Renal abscess in children: a clinical retrospective study.
AB  - A renal abscess is rare in children and diagnosis is not readily apparent before
      hospitalization, because symptoms are often insidious and nonspecific. To
      evaluate the diagnostics and therapy of renal abscess in the pediatric group, we
      will report eight cases of renal abscess in children to illustrate the variable
      features of this condition. Eight patients, 6 to 156 (mean, 45.9) months old,
      with renal abscesses in 9 kidneys were identified. Ultrasound and computed
      tomography proved to be the most valuable diagnostic tool, revealing a hypoechoic
      or hypodense mass. Fever, abdominal pain, and leukocytosis were common presenting
      features, but no child presented symptoms of loin pain. Escherichia coli was
      identified in the urine culture among the 6 cases and blood culture in one case.
      Three children were associated with mild to moderate vesicoureteral reflux. All
      patients had an intensive antibiotic treatment, which led to resolution of the
      abscess in eight of the nine kidneys. In one case, the abscess had to be drained
      using the CT-guided percutaneous drainage. During follow-up, seven children
      received 99mTc DMSA renal SPECT and only two of them had complete remission
      without sequelae of renal scar. We concluded that the renal abscesses must be
      assumed, especially, in children with prolonged fever, abdominal pain, and a high
      value of CRP. Ultrasonography is just a screening test to detect renal swelling,
      bulging, and enlargement; however, a CT scan is more sensitive and can detect
      abscess formation, as well as define the extent of the disease for planning
      conservative antibiotic treatment or additional drainage. Finally, DMSA renal
      SPECT is the best and the most sensitive examination for detecting the extension
      area of renal inflammation and correlated with the renal outcome.

PMID- 14674223
TI  - Clinical spectrum of acute respiratory distress syndrome in a tertiary pediatric
      intensive care unit.
AB  - Acute respiratory distress syndrome (ARDS) has been a great challenge in the
      field of pediatric critical care medicine. The clinical picture of children with
      ARDS in Taiwan has seldom been reported. The purpose of this study was to
      investigate the incidence, predisposing factors, clinical manifestations,
      strategies of ventilator support, adjuvant therapies, and prognosis of children
      with ARDS in a tertiary pediatric intensive care unit (PICU). A retrospective
      review of admissions to our PICU in the past 3 years showed that 16 cases met the
      criteria of pediatric ARDS. The incidence was 0.2% of all PICU admissions. The
      predisposing factors were varied, and pneumonia was the most common. The mean
      values of acute lung injury scores, ventilation indices and PaO2/FiO2 on
      admission were 3.6 +/- 0.5, 68.0 +/- 32.8 and 71.6 +/- 25.2, respectively. The
      averages of maximal peak inspiratory pressure (PIP) and positive end-expiratory
      pressure (PEEP) were 40.3 +/- 9.8 and 14.0 +/- 4.6 cmH2O, respectively. Only
      three patients (19%) expired due to overwhelming systemic infection. Compared
      with our previous high mortality rate report, we emphasized gentle mechanical
      ventilation care, early employment of high PEEP and adjuvant therapy with sodium
      nitroprusside (SNP) nebulization and/or inhaled nitric oxide (iNO) to achieve an
      improved survival rate.

PMID- 14674224
TI  - Hyperkalemia during the early postnatal days in premature infants.
AB  - Plasma electrolyte concentrations in premature infants are unstable, and
      hyperkalemia may induce significant, even life-threatening, symptoms in tiny
      infants. The medical records of 95 premature infants were retrospectively
      reviewed. Patients with a major congenital anomaly or mortality within 24 h after
      birth were excluded. Plasma electrolytes, blood urea nitrogen, creatinine, blood
      pH, urine output, and related clinical conditions during first 96 h of life were
      analyzed. Plasma potassium concentrations had significant negative correlations
      with gestational age and birth weight (p < 0.05). Infants with a gestational age
      of less than 29 weeks had significantly higher potassium concentrations (average
      5.9 +/- 0.3 mEq/L, peak 7.8 +/- 0.4 mEq/L, p < 0.05) than other gestational age
      groups, and their plasma potassium levels were significantly higher at 24 and 48
      h of age (p < 0.05). Forty-two infants (42/95, 44%) had peak plasma potassium
      concentrations greater than or equal to 6 mEq/L. With statistical analysis, the
      hyperkalemic infants comprised of significantly (p < 0.05) fewer males (31% vs.
      55%), they had more-severe respiratory distress syndrome (RDS) (grades 2 +/- 0
      vs. 1 +/- 0, p < 0.05), and needed more frequent use of inotropics (52% vs. 23%,
      p < 0.05) compared to normokalemic infants. In conclusion, hyperkalemia during
      the first 2 days of life is common in extremely premature infants. Small
      gestational age, very low birth weight, female gender, high RDS grade, need of
      exogenous surfactant and inotropic agents, delayed feeding, and a high mortality
      rate were observed in hyperkalemic infants.

PMID- 14674225
TI  - Cardiac tumors in infants and children.
AB  - Cardiac tumors in infants and children are extremely rare. Their clinical
      manifestations vary widely from asymptomatic presentations to life-threatening
      cardiac events. Improvements in diagnostic techniques, such as those offered by
      echocardiography, have made early detection of cardiac masses possible, with or
      without the presence of clinical symptoms. Fifteen pediatric cases of cardiac
      tumor were diagnosed at our institution between July 1989 and July 2002 (male
      female ratio, 10:5; age range, one day to nine years). Eleven of the cases
      involved primary cardiac tumors [rhabdomyoma (n = 10) and fibroma (n = 1)].
      Ninety percent of the rhabdomyomas (9/10) were associated with tuberous
      sclerosis. Four of the fifteen cases were secondary metastatic tumors
      [hepatoblastoma (n = 2), hepatoma (n = 1) and rhabdomyosarcoma (n = 1)]. Clinical
      manifestations of the cardiac tumors included shortness of breath (n = 5),
      seizure (n = 4), cardiac murmur (n = 6), and cyanosis (n = 3). Surgery was
      performed for three of 11 patients with primary cardiac tumor (27%) due to severe
      obstruction of flow (n = 2) and other cardiac defects (n = 1). The primary
      cardiac tumor spontaneously regressed in five of the tuberous sclerosis patients.
      All four of the patients with secondary cardiac tumors continued to receive
      chemotherapy, and only one of them subsequently experienced regression. Based on
      our experiences, we conclude that: 1) rhabdomyoma is the most common primary
      cardiac tumor in children; 2) most pediatric tumors are associated with tuberous
      sclerosis; 3) clinical presentation is determined by the tumor size and number of
      tumors, and whether expansion of the malignancy has resulted in cardiac blood
      flow obstruction; 4) there is a strong possibility of regression of the primary
      cardiac tumor, with surgery recommended only when cardiac symptoms are severe;
      and, 5) unless there is a significant obstruction of blood flow, chemotherapy is
      still the treatment of choice for secondary cardiac tumors.

PMID- 14674226
TI  - Outcome of antithyroid medication and radioiodine therapy in pediatric Graves'
      disease.
AB  - Graves' disease is a significant medical condition in children. The optimal
      therapy is controversial. We reviewed 40 pediatric patients with Graves' disease,
      5.0-17.7 yrs of age (mean 10.2 yrs), treated for at least one yr from 1990 to
      2002 to assess the outcome of antithyroid medication and radioiodine therapy. The
      follow-up duration was 1.1-11.8 yrs (mean 5.1 yrs). Clinical variables were also
      analyzed to identify the prognostic factors. The 40 patients were divided into 3
      groups according to their therapeutic options to analyze outcome. To identify
      predictors, patients who achieved remission after antithyroid drugs within 2 yrs
      (n = 7) were compared with those who received more than 2 yrs of medication but
      did not enter remission (n = 25). In group 1, 28 patients received antithyroid
      drugs for 0.7-10 yrs (mean 3.4 yrs). Fourteen (50%) achieved remission after 0.7
      6.6 yrs (mean 2.6 yrs). In group 2, 9 patients received subsequent radioiodine
      therapy (10-15 mCi) after antithyroid drugs for 1.1-9.2 yrs (mean 4.4 yrs).
      Remission was achieved after 1-11 months (mean 3.1 months) in 8 (89%). In group
      3, initial 131I (12-15 mCi) was used in 3 patients. All of them (100%) attained
      remission within 2 months. The overall remission rate of patients receiving
      medical therapy (group 1 and 2) was 38% (14/37). Of the 11 patients who achieved
      remission after radioiodine, 10 had hypothyroid status and required thyroxine
      replacement. There were no significant differences with any of the clinical
      variables that might predict remission after medication within 2 yrs, possibly
      because of the small number of patients. Our data demonstrate that radioiodine is
      an efficient and effective therapy for pediatric Graves' disease as first-line
      treatment or subsequent therapy for those with relapsed disease after medical
      therapy, although most patients develop hypothyroidism after treatment.

PMID- 14674227
TI  - Predictive inflammatory parameters in the diagnosis of acute appendicitis in
      children.
AB  - Acute appendicitis is the most common abdominal surgical emergency in children.
      In order to determine the related factors for early diagnosis of acute
      appendicitis in children, we analyzed retrospectively from January 2001 to
      December 2002 the hospital records of 260 consecutive patients under 18 years of
      age operated on because of suspected acute appendicitis. The patients group
      comprised 163 males (62.7%) and 97 females (37.3%) with a mean age of 11.1 +/-
      4.3 years (range from 0 to 18 years old). The accurate diagnostic rate of acute
      appendicitis in children was 81.5 percent and negative appendicectomy rate was
      18.5 percent. When combining leukocytosis, elevated neutrophil count and elevated
      C-reactive protein, the specificity and positive predictive value in diagnosing
      acute appendicitis were increased. According to the application of multivariate
      logistic regression analysis, the significantly related factors in acute
      appendicitis were elevated neutrophil count (Odds ratio = 3.79, 95% confidence
      interval = 1.732-8.293, p < 0.001) and elevated C-reactive protein concentration
      (Odds ratio = 2.81, 95% confidence interval = 1.231-6.390, p < 0.05). In
      conclusion, total neutrophil count and C-reactive protein may serve as predictive
      parameters for early diagnosis of acute appendicitis in children.

PMID- 14674228
TI  - Neurofibromatosis type I and intestinal neuronal dysplasia type B in a child:
      report of one case.
AB  - Constipation is a common gastrointestinal complication in type I
      neurofibromatosis (NF-1). We present a 4-year-8-month-old boy with NF-1 bothered
      by chronic episodic constipation and diarrhea since early childhood. Rectal
      suction biopsy confirmed the diagnosis of intestinal neuronal dysplasia. To our
      knowledge, this is the first Chinese child reported to have such association.

PMID- 14674229
TI  - Cardiac tamponade from percutaneous central venous catheterization: report of one
      case.
AB  - Central venous catheters (CVC) are occasionally associated with life-threatening
      extravasation complications. We report a case of cardiac tamponade in a premature
      infant complicating with percutaneous central venous catheter. The baby developed
      respiratory distress while receiving parenteral nutrition through a central
      venous line. Chest X-ray films revealed progressive increasing cardiomegaly and 2
      dimensional (2-D) echocardiography showed a "swinging heart." A diagnosis of
      cardiac tamponade was made and the baby was rescued under emergency
      pericardiocentesis and removal of the central catheter. The aspirated fluid was
      the content of parenteral fluid administered.

PMID- 14674230
TI  - Megacystis-microcolon-intestinal hypoperistalsis syndrome: report of one case.
AB  - Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a very rare
      congenital disease characterized by abdominal distension due to a dilated urinary
      bladder, microcolon and decreased or absent intestinal peristalsis. Most patients
      die at an early age. We report on a female baby with this syndrome which was
      associated with duodenal web and tracheobronchial malacia. The literature on this
      syndrome is also reviewed.

PMID- 14674231
TI  - Potocki-Shaffer syndrome: report of one case.
AB  - Potocki-Shaffer syndrome (PSS) results from deletion of proximal short arm of
      chromosome 11. We present a 14-month-old male baby with cardinal pictures of PSS
      such as bilateral parietal foraminae, abnormal craniofacial appearance, hypotonia
      and developmental delay. Cytogenetic study revealed deletion of chromosome 11
      from p11.12 to p11.2 in this proband and his mother, but microsatellite marker
      study showed deletion only in this proband. Despite previous negative chromosome
      study, positive family history with two similarly affected elder siblings and the
      finding of bilateral parietal foraminae finally lead to the etiologic diagnosis.

PMID- 14674232
TI  - Maple syrup urine disease presenting with neonatal status epilepticus: report of
      one case.
AB  - Maple syrup urine disease (MSUD) is a rare inborn error of the branched chain
      amino acid metabolism, which can be classified as classical, intermediate,
      intermittent, and thiamine responsive types. We report a 16-day-old boy who
      suffered from difficult feeding, persistent metabolic acidosis, and tricycling
      movement of the lower legs. Status epilepticus was the initial impression, but
      classical type MSUD was later diagnosed. Under the diagnosis, dietary therapy
      effectively prevented further neurological deterioration. However, amino acid
      deficiency manifested as acrodermatitis enteropathica-like skin rash occurred
      once. Early parenteral glucose supplementation and periodic plasma amino acid
      monitoring are very important in the management of metabolic diseases, including
      MSUD.

PMID- 14674234
TI  - The past and future of protein phosphatase research.

PMID- 14674233
TI  - Treatment of a pineal yolk sac tumor: report of one case.
AB  - Pineal yolk sac tumors are rare. We present a case of pineal yolk sac tumor in a
      15-year-old boy with hydrocephalus and possible cerebrospinal dissemination. He
      was treated by surgical excision, craniospinal axis irradiation, PVBE (cisplatin,
      vinblastine, bleomycin, and etoposide) chemotherapy, and intrathecal methotrexate
      chemotherapy. There was no tumor recurrence at follow-up 2.5 years after
      treatment.

PMID- 14674235
TI  - Monitoring of PP2A and PP2C by phosphothreonyl peptide substrates.

PMID- 14674236
TI  - Determination of mammalian glycogen synthase phosphatase activity.

PMID- 14674237
TI  - Measuring protein phosphatase activity with physiological substrates.

PMID- 14674238
TI  - PTEN and myotubularins: families of phosphoinositide phosphatases.

PMID- 14674239
TI  - Detection of protein histidine phosphatase in vertebrates.

PMID- 14674240
TI  - Advances in procedures for the detection and localization of inositol
      phospholipid signals in cells, tissues, and enzyme assays.

PMID- 14674241
TI  - Mixed peptide sequencing and the FASTF/FASTS algorithms.

PMID- 14674242
TI  - Phosphoproteome analysis in yeast.

PMID- 14674243
TI  - cDNA microarray analysis reveals an overexpression of the dual-specificity MAPK
      phosphatase PYST2 in acute leukemia.
AB  - The information contained in the draft sequence of the human genome offers a
      solid basis to study gene function. The DNA microarray technology is one of the
      most important tools enabling the performance of such studies. The global
      expression analysis using microarrays enables the construction of a simultaneous
      expression pattern of thousands of genes and thus an unprecedented opportunity to
      obtain molecular signatures of the state of activity of diseased cells.
      Microarray analysis may thus provide invaluable information on disease pathology,
      progression, resistance to treatment, and response to cellular microenvironments.
      Ultimately such analyses may lead to improved early diagnosis and innovative
      therapeutic approaches. Yet, by employing this advanced technology in order to
      identify new target molecules for diagnosis or therapy, one is faced with the
      necessity to focUs on one or several genes and to investigate them further. A
      huge number of differentially expressed genes are usually identified when 2 cell
      samples are comparatively analyzed in an individual assay. Several factors,
      mainly a possible genetic diversity between the samples, minimize the capability
      of reaching an educated conclusion as to which gene or genes to select for
      further studies. Gene expression arrays were employed to identify genes whose
      expression characterizes leukemic leukocytes. Many different genes were
      differentially expressed by "leukemic-phase leukocytes," derived from three
      untreated acute myelogenous leukemia (AML) patients and by "remission-phase
      leukocytes," obtained from the same patients following induction of remission.
      However, only two of these genes, the dual-specificity MAPK phosphatase PYST2 and
      the tryptophan 5-hydroxylase, were found to be more highly expressed by the
      leukemic-phase than by remission-phase leukocytes of all three patients. The
      microarray results of only the PYST2 gene could be verified by RT-PCR. By
      focusing on genes that had a similar expression pattern in cells from multiple
      donors we overcame the problem of genetic diversity and identified, out of 60
      differentially expressed genes, a single candidate target gene in AML. Pooling
      specimens in order to overcome the problem of genetic diversity (e.g., clinical
      material obtained from treated patients and from untreated ones), is not
      recommended because it may dilute the treatment effects. Therefore, it is
      essential to perform each experiment using individual preparations.

PMID- 14674244
TI  - Protein phosphatase translocation in RBL-2H3 cells.

PMID- 14674245
TI  - Whole mount analysis of mammary gland structure in PTP epsilon transgenic mice.

PMID- 14674246
TI  - Assay of protein phosphatase 1 complexes.

PMID- 14674247
TI  - Validation of interactions with protein phosphatase-1.

PMID- 14674248
TI  - Analysis of specific interactions of native protein phosphatase 1 isoforms with
      targeting subunits.
AB  - Expression of recombinant PP1 isoforms with fully authentic properties has proven
      to be a challenge for several laboratories. In order to circumvent this technical
      limitation in the investigation of isoform-specific roles for PP1, methods have
      been developed to analyze specific properties of native PP1 isoforms. The well
      documented method of ethanol precipitation of tissue extracts has been used to
      dissociate phosphatase catalytic subunits from their endogenous regulatory
      subunits and other cellular proteins. Although very low levels of PP1 and PP2A
      regulatory subunits are sometimes detected in PPC preparations, they are not
      associated with their respective catalytic subunits because they do not copurify
      with the catalytic subunits on microcystin-Sepharose (Bauman & Colbran, not
      shown). Thus, the PPC preparation represents a mixture of native monomeric
      phosphatase catalytic subunits (including PP1 isoforms, PP2AC, PP4C, and PP6C)
      that can be used to analyze their interactions with other proteins. The methods
      described in this report rely on the availability of highly specific antibodies
      to PP1 isoforms. The sheep antibodies have previously proven effective for
      immunoblotting and immunoprecipitation, whereas rabbit antibodies have also been
      used for immunocytochemistry. This paper documents the use of these antibodies in
      Far-Western overlay and glutathione-agarose cosedimentation assays to investigate
      interactions of specific PP1 isoforms with recombinant fragments of PP1-targeting
      subunits (spinophilin, neurabin and GM). Moreover, covalent coupling of affinity
      purified sheep antibodies to agarose provided a means for the immuno-isolation of
      PP1 beta and PP1 gamma 1 from the PPC preparation. Active catalytic subunits are
      recovered from the affinity resin using chaotropic agents, permitting for the
      first time the assessment of the effects of specific targeting subunits on
      activities of individual native PP1 isoforms. These methods have been used
      successfully to demonstrate that some PP1-interacting proteins discriminate among
      the isoforms. The isoform inhibition assays provide a measure of the binding
      equilibrium in the milieu of the phosphatase assay. For example, while some PP1
      binding proteins inhibit native PP1 beta and native PP1 gamma 1 with equivalent
      potency (e.g., PKA-phosphorylated inhibitor-1), spinophilin, neurabin and GM
      differentiate between these two isoforms; spinophilin and neurabin fragments
      inhibit native PP1 gamma 1 approximately 20-fold more potently than they inhibit
      native PP1 beta (Fig. 4), whereas GM inhibits native PP1 beta more potently than
      native PP1 gamma 1 (not shown). Moreover, the activity of native PP1 gamma 1 is
      approximately 100-fold more sensitive to neurabin and spinophilin than is the
      activity of bacterially-expressed recombinant PP1 gamma 1 (Fig. 4). The
      interpretation of these inhibition assays is consistent with data obtained in Far
      Western overlay (Fig. 2) and glutathione-agarose cosedimentation assays (Fig. 3),
      which assess more stable interactions of PP1 isoforms. Thus, spinophilin and
      neurabin selectively bind PP1 gamma 1 over PP1 beta, whereas GM is highly
      selective for PP1 beta. These data are consistent with previous experiments that
      showed spinophilin and neurabin are present in PP1 gamma 1 complexes in brain
      extracts, but not in PP1 beta complexes. Moreover, only PP1 beta has been
      identified in complexes with GM in muscle extracts, although these data did not
      exclude the possibility that other isoforms were also present. Presumably, these
      isoform-selective interactions confer different functions on PP1. In summary, we
      have developed methods that should prove useful in defining the isoform
      selectivity of other PP1-targeting subunits. Moreover, these methods may be
      employed to identify domains in PP1-interacting proteins that confer isoform
      specificity. Similar strategies may also be used to explore interactions of
      protein phosphatase catalytic subunits with other proteins.

PMID- 14674249
TI  - Using the Ras Recruitment System to identify PP2A-B55-interacting proteins.
AB  - The RRS system facilitated the discovery of hitherto unknown interactions with
      the PP2A-B55 subunit. The advantages of the system lie in its ability to identify
      interactions that may not be detected by traditional yeast two-hybrid systems.
      The RRS can thus provide a complementary genetic approach to the identification
      of protein-protein interactions.

PMID- 14674250
TI  - Altering the holoenzyme composition and substrate specificity of protein
      phosphatase 2A.

PMID- 14674251
TI  - The application of fluorescence resonance energy transfer to the investigation of
      phosphatases.

PMID- 14674252
TI  - Receptor protein-tyrosine phosphatase dimerization.

PMID- 14674253
TI  - Phosphoprotein inhibitors of protein phosphatase-1.

PMID- 14674254
TI  - Combinatorial chemistry and peptide library methods to characterize protein
      phosphatases.

PMID- 14674255
TI  - Activity of PP2C beta is increased by divalent cations and lipophilic compounds
      depending on the substrate.

PMID- 14674256
TI  - Regulation of calcineurin by oxidative stress.

PMID- 14674257
TI  - Analysis of the regulation of protein tyrosine phosphatases in vivo by reversible
      oxidation.

PMID- 14674258
TI  - Preparation and characterization of recombinant protein phosphatase 1.

PMID- 14674259
TI  - An inducible system to study the growth arrest properties of protein phosphatase
      2C.

PMID- 14674260
TI  - Use of tetracycline-regulatable promoters for functional analysis of protein
      phosphatases in yeast.

PMID- 14674261
TI  - Analysis of protein phosphatase function in Drosophila cells using RNA
      interference.
AB  - Double stranded RNA-mediated RNA interference is an effective method to
      downregulate the levels of protein phosphatases in Drosophila S2 cells. In many
      cases, nearly complete ablation of the targeted protein can be achieved. RNAi
      mediated knockdown of protein phosphatases is akin to pharmacological inhibition
      with drugs and can be used to determine the roles of specific protein
      phosphatases in intact cells. RNAi can avoid the problems associated with less
      than adequate specificity of phosphatase inhibitors. Although information about
      the signaling pathways present in Drosophila S2 cells is not as well developed as
      many mammalian cell lines, the Drosophila system is particularly attractive for
      the study of oligomeric phosphatases like PP2A. Drosophila has far fewer isoforms
      for the phosphatases we have examined. This is especially true of the genes for
      PP2A regulatory subunits where over 50 isoforms are present in mammals but only
      four are present in Drosophila. Once hypotheses regarding phosphatase function
      have been generated from RNAi experiments in S2 cells, they can potentially be
      tested utilizing recent advances in the use of siRNAs to conduct RNAi experiments
      in mammalian cell lines. RNAi in Drosophila S2 cells has proven to be a powerful
      technique for identifying physiological functions of signaling proteins. The RNAi
      method is straightforward and works routinely with almost all proteins. RNAi in
      S2 cells can be used to assess the role of signaling proteins in specific
      pathways and as a screening tool to identify new roles for signaling molecules.
      For example, results from RNAi analysis of PP2A show that regulation of MAP
      kinase signaling involves the R2/B regulatory subunit and that the R5/B56
      subunits play a previously unidentified role in apoptosis. While RNAi in
      Drosophila S2 cells is a powerful tool for analyzing protein function, the method
      does have limitations. Foremost, cells may exhibit an RNAi response to any
      nonspecific dsRNA, even in the absence of interferon. Therefore, physiological
      processes that respond to nonspecific dsRNA will be difficult to study. A second
      limitation is the need to produce antibodies that react with Drosophila isoforms.
      We have found that many antibodies to mammalian protein phosphatases do not cross
      react with the corresponding Drosophila proteins. Finally, the physiology and
      signaling pathways of S2 cells have not been extensively studied. This lack of
      information limits the number of available readouts that can be used when
      assessing the effects of protein knockdowns.

PMID- 14674262
TI  - Regulating the expression of protein phosphatase type 5.

PMID- 14674263
TI  - Transgenic and knockout models of PP2A.

PMID- 14674265
TI  - Transformations in structural biology: a personal view.

PMID- 14674264
TI  - Saccharomyces gene deletion project: applications and use in the study of protein
      kinases and phosphatases.

PMID- 14674266
TI  - Origins.

PMID- 14674267
TI  - Personal X-ray reflections.

PMID- 14674268
TI  - Robotics for automated crystal formation and analysis.

PMID- 14674269
TI  - Use of limited proteolysis to identify protein domains suitable for structural
      analysis.

PMID- 14674270
TI  - Solvent entropy effects in the formation of protein solid phases.

PMID- 14674272
TI  - Counterdiffusion methods for macromolecular crystallization.

PMID- 14674271
TI  - Controlling biomolecular crystallization by understanding the distinct effects of
      PEGs and salts on solubility.

PMID- 14674273
TI  - Growth sectors and crystal quality.

PMID- 14674274
TI  - Molecular mechanisms of defect formation.

PMID- 14674275
TI  - Cryocooling of macromolecular crystals: optimization methods.

PMID- 14674276
TI  - The well-tempered protein crystal: annealing macromolecular crystals.

PMID- 14674277
TI  - What can I have as a source of X-ray synchrotron radiation? A primer for
      potential users.

PMID- 14674279
TI  - Macromolecular crystal quality.

PMID- 14674278
TI  - Protein crystal structure analysis from high-resolution X-ray powder-diffraction
      data.
AB  - Although high-resolution powder diffraction of proteins is in its infancy, we can
      easily see future developments of the method that will allow examination of
      protein structures that exceed 100 kDa. In particular, current data-collection
      technology scans the powder-diffraction pattern a few points at a time over a
      very narrow field of view. The use of high-resolution imaging technology and X
      ray focusing optics should improve this 1000-fold or more, making it possible to
      use powder diffraction on a laboratory X-ray source to screen for the formation
      of protein/drug complexes and to determine their structures.

PMID- 14674280
TI  - Protein structures at atomic resolution.

PMID- 14674281
TI  - [Bayesian methodology: an alternative to regular medical practice].
AB  - The Bayes theorem provides a formula to calculate the probability of an event to
      occur conditioned by the occurrence of an anterior one (conditioned probability).
      In medicine it has been applied to calculate the probability of suffering a
      disease when having a positive result in a given test. This formula emphasizes
      the importance of prevalence of a disease (or a priori probability of the
      positive predictive value of a diagnostic test). The novelty of applying the
      bayesian methodology in clinical practice results from taking into consideration
      previous external information (or "a priori probability"), and to calculate how
      it is modified by the evidence (or "verisimilitude") provided by certain
      empirical tests, to obtain a new probability conditioned by the empirical
      evidence (or "a posteriori probability"). It also allows to perform sequential
      analysis (repeated observation of a given event a number of times not fixed in
      advance) and to incorporate the subjective probabilities to the reasoning. Some
      authors have proposed the use of bayesian methodology in research studies, such
      as clinical trials. Nevertheless, this methodology does not adapt well to this
      kind of reasoning which is hypothetical-deductive.

PMID- 14674282
TI  - [Macrophages in human semen].
AB  - OBJECTIVES: To investigate the presence of macrophages in human semen samples and
      the function they carry out in the seminal fluid. Their presence was studied in
      relation to spermatic morphology, percentage of spermatozoids with native DNA,
      and presence of antispermatic antibodies. METHODS AND RESULTS: The work was
      performed with semen samples from 31 unfertile males from 63 couples in which the
      "female factor" was ruled out as the cause of infertility. Sperm study according
      to WHO (1992) was carried out in all samples, in addition to: DNA study with
      acridine orange as fluorocrom, macrophage concentration by neutral red in a
      Neubauer camera, and detection of antispermatic antibodies with a mixed
      agglutination test (TAC II) (validated with Mar Screen-Fertility technologies).
      Sperm morphology was evaluated by Papanicolaou test. 19/31 selected sperm samples
      (61.3%) showed increased concentration of macrophages, 13 of them (41.9%) with
      denaturalized DNA, and 8 (25.8%) abnormal morphology. Six samples showed
      increased macrophage concentration and predominance of native DNA, whereas 11
      samples showed increased macrophages and abnormal morphology. Among 18 (58.1%)
      samples showing antispermatic antibodies 14 (77.7%) had an increased
      concentration of macrophages. Statistical analysis resulted in a high correlation
      between macrophage concentration and increased percentage of spermatozoids with
      denaturalized DNA (p < 0.05). An increased concentration of macrophages is
      associated with the presence of antispermatic antibodies (p < 0.05). There was
      not evidence of significant association between concentration of macrophages and
      percentage of morphologically normal spermatozoids (p < 0.05). CONCLUSIONS: We
      can conclude that macrophages are present in human semen and participate in
      immunovigilance contributing to improve the seminal quality.

PMID- 14674283
TI  - [AMS-800 artificial sphincter. Our experience in the last 20 years].
AB  - OBJECTIVE: To present a series of 63 patients with urinary incontinence due to
      sphincteric incompetence who underwent the implantation of an AMS-800 artificial
      sphincter. METHODS: From 1984 to December 2002 a total of 69 patients received
      this prosthesis, 63 of which were available for review. The cause of incontinence
      was sphincter incompetence in all cases, said secondary to prostate surgery,
      neurogenic bladder, post-traumatic urethral lesion, and epispadias. 52 of them
      were placed in the bulbar urethra, and 11 in the bladder neck. The cuff diameters
      varied from 4 to 10 cm and reservoir pressures from 51-60 to 71-18 H2O cm.
      RESULTS: The complications that appeared, ordered by frequency, were:
      malfunction, infection and rejection or exteriorization, fistula, and
      unappropriate size. The total number of reoperations was 39 in 28 patients.
      Functional results were successful in 48 cases and failure in 15. CONCLUSIONS:
      The use of an AMS-800 prosthesis for the treatment of urinary incontinence due to
      sphincteric incompetence is effective but not without complications. The most
      frequent indication was following prostate surgery, being this group the one that
      obtains the best results. Patients with incontinence of neurogenic origin have
      the highest complication rate, and the worst results in relation to
      vascularization and tissue trophism abnormalities. In female patients we prefer
      other techniques that have similar results, are technically easier and more
      economic.

PMID- 14674284
TI  - [Urachal cyst. Current status].
AB  - OBJECTIVES: We report one case of urachus diverticulum. It is very rare in adults
      so that the level of diagnostic suspicion is low. METHODS: 50-year-old male
      without history of urologic diseases who presented with recurrent urinary tract
      infections over a two-year period. There were not findings on physical
      examination. Abdominal ultrasound showed a 3 x 2 cm cystic image with internal
      echoes on the bladder dome. CT scan confirmed the cystic lesion which thickened
      the bladder wall at the dome. The patient underwent surgery for the excision of a
      suspected urachal cyst. RESULTS AND CONCLUSIONS: In order of frequency, the 4
      types of urachal congenital abnormalities are: permeable urachus (50%), urachal
      cyst (30%), urachal sinus (15%), and urachal diverticulum (5%). The indication of
      surgery comes from the possibility of infection and malignant transformation; the
      cyst should be excised with a bladder dome cuff due to the risk of existence of
      urachal remnants at that level and their potential to degenerate to
      adenocarcinoma.

PMID- 14674285
TI  - [Renal adenocarcinoma. Prognostic factors].
AB  - OBJECTIVES: To perform a descriptive analysis of 57 cases of renal adenocarcinoma
      treated in our department, trying to identify those variables that modify
      survival, and to evaluate the impact of incidental diagnosis on survival.
      METHODS: 57 cases of renal cell carcinoma treated in our department from 1996 to
      2001 were retrospectively reviewed. Mean follow-up time was 30 months. The impact
      on survival of incidental diagnosis, stage, and other variables was evaluated. We
      used the chi-square test to study the association between qualitative variables,
      and the prevalence proportion with 95% confidence intervals to quantify the
      magnitude of the association. RESULTS: Mean age on presentation was 63 +/- 12.57
      yr. The most frequent histological type was classic renal cell carcinoma (83.6%).
      hematuria was the presenting sign in most cases. 19.3% were incidentally
      diagnosed with a 24 month survival was 100% in comparison to 59% of the patients
      presenting with clinical signs/symptoms (p = 0.0218); 24 month survival rates for
      stages I-II was 95.83% in comparison to 48.48% for stage III-IV. CONCLUSIONS:
      Renal cell adenocarcinoma is an aggressive tumor with a variety of clinical
      presentations which delay its diagnosis. Tumor stage is one of the main
      prognostic factors. Nowadays, the greater availability of radiological tests,
      mainly ultrasounds, has resulted on an increase in the number of incidental
      diagnosis and therefore a greater number of early stages; it is advisable to
      perform a renal pathology screening on every patient who undergoes abdominal
      ultrasound for any other reason.

PMID- 14674286
TI  - [Treatment of vesicoureteral reflux in patients with neurogenic bladder. Should
      the ureter be reimplanted in patients treated with augmentation cystoplasty?].
AB  - OBJECTIVES: To evaluate the necessity of performing ureteral reimplantation in
      patients with vesicoureteral reflux secondary to neurogenic bladder. METHODS:
      Retrospective review of 19 patients (10 males and 9 females), between 2 and 19
      years of age (Mean age 7 years), with neurogenic bladder and vesicoureteral
      reflux (VUR) treated from May 1990 to July 2000. No one patient had a
      satisfactory response to the therapy with anticholinergic drugs and clean
      intermittent catheterization. All 19 patients underwent augmentation cystoplasty
      (15 using sigmoid colon and 4 ureter). Ten patients, 16 renal units, underwent
      simultaneous ureteral reimplantation. RESULTS: All patients improved their
      bladder capacity and compliance after bladder augmentation. VUR disappeared in 17
      patients. Two patients (3 renal units) in the group without ureteral
      reimplantation remained with a minor degree of reflux. CONCLUSIONS: Bladder
      augmentation alone resolves VUR secondary to neurogenic bladder in a high
      percentage of patients.

PMID- 14674287
TI  - [Rationale of Doppler urodynamics and urodynamics. What does Doppler contribute
      to urodynamics?].
AB  - OBJECTIVES: To make an analysis of the usefulness of urodynamic tests and what
      can be obtained from them. METHODS: We also perform and analytical deduction of
      those parameters that define detrusor behavior, such as the constant defining
      bladder compliance, the bladder elastic constant, in its tensile properties, and
      we found the expression of resistances and calculate the abdominal pressure
      formula; therefore we don't need to introduce a rectal catheter to know the value
      of those parameters that define bladder dynamics. RESULTS: Although they are
      provisional, they allow foreseeing a promising future for this application of a
      well-known device. CONCLUSIONS: Currently, we can only define the bladder
      behaviour, its resistances, the detrusor drive and compliance with the only
      discomfort of a perineal Doppler ultrasound. Time will open new possibilities.

PMID- 14674288
TI  - [Current view and critic of alternatives to transurethral surgery of prostatic
      benign prostate].
AB  - OBJECTIVES: Critical update of transurethral surgery options based on the last
      decade most relevant bibliography. METHODS: Comparative study between
      Incision/TUR of the prostate and alternative techniques, accordingly to data from
      30 randomized studies and 28 clinical studies. We evaluate efficiency,
      retreatment index, morbidity, post operative number of days with catheter,
      anesthetic requirements, and cost. Data are expressed as percentages resulting
      from a differential formula in randomized studies and simple percentages or
      numeric expression for relevant clinical data. RESULTS: Efficiency: all
      alternative treatments show a symptomatic improvement (> 50%) similar to that
      achieved by transurethral surgery; post treatment flowmetry percentage increase
      is inferior in all alternatives except vaporization, holmium laser and
      prosthesis. Re-Treatment requirements: they were higher in all alternatives
      except the ablative ones (vaporization and holmium laser). Morbidity: all of them
      had an operative estimated blood loss inferior to TUR and similar to prostatic
      incision; contact laser and vaporization had more irritative symptoms than
      incision, and VLAP and TUMT more than TUR; TUMT and interstitial laser have a
      higher rate of post operative infection; all alternatives except the ablative
      ones had lower percentages of urethral stenosis and retrograde ejaculation.
      Number of days of catheter post operative: it was comparatively longer after
      vaporization and very long after VLAP, interstitial laser and TUMT. All
      treatments except TUNA and TUMT require the same anesthesia than transurethral
      surgery. The cost/benefit has not been sufficiently evaluated, but it is superior
      with holmium laser, contact laser and vaporization than with transurethral
      surgery. CONCLUSIONS: Based on study data we can accept holmium laser as a real
      alternative, TUMT in cases when surgery is questioned and intraprostatic
      prosthesis when it is not possible.

PMID- 14674289
TI  - [Vesicocapsuloplasty: technical variation of retropubic surgery for benign
      prostatic hypertrophy. Preliminary report].
AB  - OBJECTIVES: To report a technical variation in the retropubic adenomectomy
      operation which improves the standards for this type of open surgery
      significantly. METHODS: We review the charts of the last 35 patients undergoing
      surgery with this technical variation, with a minimum follow-up of one year,
      following a pooled experience of 1033 cases of retropubic open surgery for BPH by
      the hemostatic transcervical adenomectomy technique. RESULTS/CONCLUSIONS: During
      surgery this variation allows a better access to the prostatic bed facilitating
      direct haemostasis and search for adenoma remnants. In the same way it allows to
      perform prostate biopsies in those cases of BPH with PSA values over normal range
      and previous negative biopsies. Finally, "vesicalization" of the prostatic bed
      contributes to avoid post operative spasms and it would be the anatomical basis
      for avoidance of bladder neck retraction in the middle term. With all
      reservations implied in the application of a recent technical variation, the
      limited number of cases, and short follow-up, we may say that significant
      improvements have been seen in immediate standards such as intraoperative and
      postoperative blood loss, bladder spasms, post surgical analgesics requirements,
      and hospital stay reduction.

PMID- 14674290
TI  - [Urethral recurrence of transitional carcinoma in a cystectomized patient].

PMID- 14674291
TI  - [Renal fibrosarcoma. Report of a case].
AB  - OBJECTIVES: To describe one case of renal fibrosarcoma in a patient who presented
      with left flank pain, fever and palpable mass. We review clinical data,
      diagnosis, therapeutic aspects and prognostic factors for this type of tumor.
      METHODS: The study of the patient included intravenous urography, ultrasound, and
      CT scan. Left radical nephrectomy was performed. RESULTS: The patient remained
      asymptomatic for 14 months, but then presented with a tumor in the frontal
      parietal area, dying ten months later due to generalized metastasis. CONCLUSIONS:
      Fibrosarcoma is an rare malignant tumor arising from renal mesenchyma with poor
      prognosis. In radiological tests renal sarcomas show malignant tumor
      characteristics, but without a specific histology they cannot be differentiated
      from a renal cell carcinoma.

PMID- 14674292
TI  - [Genital injury. Report of a case].
AB  - OBJECTIVES: We report a new case of severe genital trauma to analyze the most
      frequent causes of genital area traumatisms and their main presentations in the
      emergency department. METHODS/RESULTS: A patient who presents to our hospital
      with severe genital laceration caused by a farm machine during his work. We
      describe clinical picture, surgical treatment, and clinical outcome. The result
      was satisfactory. CONCLUSIONS: An analysis of this pathology is carried out:
      classifications, decision taking in the emergency department and also surgical
      treatment for reconstruction if necessary.

PMID- 14674293
TI  - [Acute obstructive kidney failure after kidney transplantation caused by calculi
      transfer from donor].
AB  - OBJECTIVES: To report one case of lithiasis transference from the donor
      associated with renal transplant. METHODS: 53-year-old female with obstructive
      uropathy within the first post transplant month. RESULTS/CONCLUSIONS: Lithiasis
      transference after transplant is a cause of early obstructive uropathy after
      kidney transplantation. The low the incidence of lithiasis transference does not
      justify the performance of x-ray and/or ultrasound of the donor organ in terms of
      cost effectiveness. Extracorporeal shockwave lithotripsy is a valid therapeutic
      option on transplanted kidneys.

PMID- 14674294
TI  - [Liposarcoma of the perirenal cell].
AB  - OBJECTIVES: To show the imaging tests characteristics and differential diagnosis
      of masses located within the retroperitoneal perirenal area. METHODS: Diagnostic
      imaging tests (KUB x-ray, ultrasound, helical CT scan with IV contrast) and
      follow-up in one case of perirenal cell liposarcoma. RESULTS: The study of the
      surgical specimen after renal tumorectomy in a patient with a solitary kidney
      resulted in the present diagnosis. CONCLUSIONS: Liposarcoma is a malignant
      neoplasia derived from fatty tissue. Approximately 13% are located in the
      retroperitoneal area, and less than 1/3 arise from perinephric fat. We report one
      case of liposarcoma located in the perirenal cell as an incidental finding during
      contralateral psoas muscle abscess follow-up in a patient with a solitary kidney
      after surgery for xanthogranulomatous pyelonephritis. Successive controls during
      the last year allowed us to evaluate the evolution of this lesion's.

PMID- 14674295
TI  - [Prostatic ductal carcinoma].
AB  - OBJECTIVES: We presented one case of prostatic adenocarcinoma of ductal origin,
      known as endometrial adenocarcinoma before. The first case was published in 1967
      by Mellicow. Since then we could only recover 8 cases by spanish authors.
      METHODS/RESULTS: 61-year-old patient presenting with urethral bleeding, PSA 12
      ng/cc, and an exophytic urethral mass. Histology was compatible with ductal
      adenocarcinoma of the cribiform type. Radical prostatectomy was carried out with
      good outcome at six months follow up. CONCLUSIONS: Prostatic ductal
      adenocarcinoma is a rare tumor, accounting for 0.2-5% of prostatic tumours. Its
      behaviour is variable, similar to the acinar cell type. Strikingly, there are
      scarce references to this tumor type; accordingly to the statistics of incidence
      it should have been referred more often, which would help to its study in terms
      of outcomes, treatment, and prognosis.

PMID- 14674296
TI  - [Dissecting aneurysm of the renal artery in patient with transplantation. Report
      of a case. Review of the literature].
AB  - OBJECTIVES: Aneurysmatic processes of the renal artery after transplant are rare
      entities, generally secondary to technical defects or infectious pictures. Among
      other presentations, dissecting aneurysm are exceptional, having a particularly
      difficult diagnosis due to the lack of specific clinical data which could
      differentiate them from other processes such as graft rejection or acute tubular
      necrosis, as well as the absence of characteristic representative images.
      METHODS: We report one case of dissecting aneurysm after a kidney transplant
      resulting in graft loss. RESULTS: We analyze the presentation form, diagnostic
      procedures, pathologic studies, and possible therapeutic options. CONCLUSIONS:
      Dissecting aneurysm of the renal artery is a rare entity of difficult diagnosis
      due to the poorness of presenting symptoms and the difficulty of finding it in
      routine tests, being necessary to think of it and to perform angiography as the
      only diagnostic test. Treatment is carried out by hilar reconstruction or
      transplant nephrectomy when the former is not possible.

PMID- 14674297
TI  - [Spontaneous pneumopyelography for enteroureteral fistula].
AB  - OBJECTIVES: To report one outstanding case of fever and flank pain with the
      radiologic finding of air outlining the whole left upper urinary tract
      (pneumopyelography). METHODS: The patient subject of this case had a history of
      gynaecologic surgery five years before presentation and subsequent diverticulitis
      one year later requiring discharge colostomy followed by reconstruction 7 months
      later. We performed a MEDLINE search using the terms "entero urinary fistula".
      Most papers are case reports with reviews of the diagnostic and therapeutic
      procedures, as well as the etiologic factors. RESULTS: Radiologic tests are key
      to make this finding clear and to determine its location. In our patient, once
      the acute picture was controlled and the confirmatory diagnosis was made by means
      of barium enema, we proceeded with left simple nephrectomy and lower intestine
      resection including the fistula tract. Real incidence is unknown; there is a
      female predominance in the published cases. Depending on the casual mechanism,
      they may be classified as spontaneous or traumatic. Most of them are secondary to
      bowel inflammatory diseases like diverticulitis, Crohn's disease, tumors,
      ulcers,... They can also be secondary to impacted urinary lithiasis, urothelial
      tumor, endoscopic procedures, etc. Other cases are secondary to previous surgery
      and radiotherapy. CONCLUSIONS: The finding of pneumopyelogram should prompt and
      interventional algorithm including radiologic tests and other examinations to
      allow a proper diagnosis and to perform an effective treatment.

PMID- 14674298
TI  - An unusual tumor of the spermatic cord: myositis ossificans.
AB  - OBJECTIVES: Tumors of the spermatic cord and epididymis are rare, and their exact
      incidence is difficult to determine. Ninety percent of extra testicular tumors
      within the scrotum are found in the spermatic cord, where 30% is malignant (1).
      METHODS: In this case report we present an unusual spermatic cord tumor, i.e.
      myositis ossificans (MO). To the best of our knowledge, MO of the spermatic cord
      has not been reported before in the literature. CONCLUSIONS: MO should be
      considered in the differential diagnosis of the spermatic cord tumors.

PMID- 14674299
TI  - Examining international perspectives on quality care.
AB  - Many of the top issues related to quality healthcare are problems not just in the
      American health system but throughout the world as well. This issue highlights
      some of those international issues, including patient safety and nurse staffing,
      and how larger solutions also can be applied locally at the hospital or health
      system level.

PMID- 14674300
TI  - Variations in quality causing needless deaths, new annual NCQA report says.
AB  - The National Committee for Quality Assurances (NCQA's) annual assessment of
      healthcare quality noted some good news and some bad news for the healthcare
      community. For the good news, more health plans and providers are approaching
      optimal results for several measures related to cardiovascular care and cancer
      prevention. However, failure of all plans to deliver the right preventive or
      follow-up care for other common conditions--such as diabetes and high blood
      pressure--means that more than 57,000 Americans are dying unnecessarily every
      year, NCQA estimated.

PMID- 14674301
TI  - Pheochromocytoma. Pathophysiology and clinical management. Preface.

PMID- 14674302
TI  - Principles of catecholamine biosynthesis, metabolism and release.

PMID- 14674303
TI  - Pathogenesis of pheochromocytoma.

PMID- 14674304
TI  - The genetic basis of pheochromocytoma.
AB  - Until very recently, the majority of hereditary pheochromocytomas were related to
      the MEN 2 and the VHL. In rare instances, hereditary pheochromocytoma was
      reported in patients with NF1. In addition, nonsyndromic hereditary
      pheochromocytomas have been reported. Recently, three more genes (SDHD, SDHB, and
      SDHC) which are all related subunits of the mitochondrial complex II have been
      identified to cause susceptibility to pheochromocytoma and/or paraganglioma.
      Hence, mutation analysis of VHL, RET, SDHB, and SDHD is generally recommended in
      patients with pheochromocytoma regardless of their family history or other
      features suggestive for a hereditary form. Mutation analysis should start with
      VHL and RET. However, in the presence of extra-adrenal pheochromocytoma, it may
      be more useful to screen for VHL, SDHD and SDHB mutations. It is of interest that
      various different genes can lead to one type of tumor formation. A common pathway
      (i.e. oxygen sensing) has been shown for VHL and SDHX. However, although several
      genes that are involved in the pathogenesis of hereditary pheochromocytoma are
      known, the precise molecular steps in tumorigenesis are widely unknown. In
      addition, recent data in MEN 2 pheochromocytomas point to a 'second hit'
      mechanism as a trigger for tumor formation. The molecular pathogenesis of
      sporadic pheochromocytomas remains obscure [114].

PMID- 14674305
TI  - The clinical presentation (symptoms and signs) of sporadic and familial
      chromaffin cell tumours (phaeochromocytomas and paragangliomas).

PMID- 14674306
TI  - Biochemical diagnosis of pheochromocytoma.

PMID- 14674307
TI  - Diagnostic imaging of pheochromocytoma.

PMID- 14674308
TI  - Preoperative and surgical therapy in sporadic and familial pheochromocytoma.

PMID- 14674309
TI  - Somatostatin receptors in pheochromocytoma.

PMID- 14674310
TI  - Malignant pheochromocytoma.

PMID- 14674311
TI  - [Definition of chronic obstructive disease].
AB  - COPD is a name proposed by two American doctors, M.H. Williams and N.S. Seriff,
      to describe a disease entity combining chronic bronchitis and pulmonary
      emphysema, manifested in patients as an obstructive ventilatory disorder with a
      main symptom of chronic dyspnea. Since the 1970s, COPD has been considered a
      smokers' disease brought on chiefly by the chronic stimulation of tobacco smoke.
      In 2001, the GOLD guideline indicated that COPD should not refer to a disease
      combining chronic bronchitis and pulmonary emphysema, but rather to a disease
      state characterized by an airflow limitation that is not fully reversible.
      Nonetheless, problems still remain in defining this disease entity.

PMID- 14674312
TI  - [Prevention of chronic obstructive pulmonary disease (primary prevention and
      secondary prevention)].
AB  - Cigarette smoking is the major risk factor for chronic obstructive pulmonary
      disease (COPD). The prevention of smoking initiation among teenagers and the
      encouragement of smoking cessation among smokers lead to preventing the onset and
      progression of COPD. Smoking cessation is the single most effective- and cost
      effective-way to reduce the risk of developing COPD and stop its progression.
      Comprehensive tobacco control policies and programs, which involve some mix of
      public education, mass media campaigns, prevention of youth access to tobacco,
      school-based smoking prevention curricula, creation of smoke-free environment,
      and health professional training on cessation techniques should be delivered.

PMID- 14674313
TI  - [COPD guideline of Japanese Respiratory Society].
AB  - Standard for the diagnosis and care of patients with chronic obstructive
      pulmonary disease (COPD) was published from Japanese Respiratory Society in 1999.
      In this guideline the definition, epidemiology, risk factors, pathology, methods
      of diagnosis, methods of therapy and care were fully described. Especially, in
      this guideline, we used the thin slice CT for the diagnosis and classification of
      disease severity. After the publication, this guidelines were distributed to all
      of the JRS members(about 10,000 doctors).

PMID- 14674314
TI  - [Epidemiology of chronic obstructive pulmonary disease in Japan--international
      comparison].
AB  - Substantial variation among countries has been reported regarding mortality data
      for COPD in industrialized countries. Differences in COPD death rates among
      countries have attracted considerable attention, with multiple suggested
      hypothesis, including smoking behaviors, air pollution, respiratory infections
      and genetic factors. However, the lack of standardization of death certification
      as well as differences among countries in diagnostic standards of COPD, could
      limit the interpretation of the data. No meaningful international comparisons of
      COPD prevalence can be possible until a GOLD initiative bring information about
      COPD to public health officials, the medical community, and the public throughout
      the world. No comparable data regarding the COPD epidemiology such as Nippon COPD
      Epidemiology(NICE) study, has been available in other countries than Japan. NICE
      study indicated that most of COPD cases(90%) are undiagnosed, and a significant
      attention will be required to raise awareness of COPD.

PMID- 14674315
TI  - [Stage and prognosis of COPD].
AB  - Clinical stages of chronic obstructive pulmonary disease(COPD) have been
      described in the guideline by American Thoracic Society(ATS), European
      Respiratory Society(ERS), and Japanese Respiratory Society. Recently, the
      clinical stage in GOLD(Global Initiative Obstructive Lung Disease) was also
      published in the guideline as an international standard. Although severity or
      clinical stages of COPD in ATS, ERS, and JRS guidelines is determined by only %
      predicted FEV1.0/FVC(%FEV1.0), GOLD guideline added clinical symptoms to %FEV1.0
      for determining clinical stages of COPD. Prognosis is also correlated with
      %FEV1.0 in COPD patients. Prognosis of COPD patients shows a clear decline in
      proportion to that of %FEV1.0. However, pulmonary circulation disorder also
      affects the prognosis of COPD. Pulmonary hypertension is often found in severe
      COPD.

PMID- 14674316
TI  - [Role of genetic factors in the development of COPD].
AB  - As only a small portion of smokers develop clinically-apparent COPD, there should
      be some factors relevant to the susceptibility to smoking. Several studies have
      demonstrated an increased risk of COPD within families of COPD probands. Recent
      exploratory studies have revealed a number of candidate genes that may influence
      a person's risk of COPD, including MMP-9, microsomal epoxide hydrolase,
      glutathione S-transferase, hemeoxygenase, and TNF-alpha. However, the results
      from other laboratory are often inconsistent, and there have been no genes except
      alpha 1-antitrypsin, which have been definitely confirmed to explain the
      susceptibility to smoking in the development of COPD. It is of note that the
      susceptibility to smoking could be explained also by non-genetic factors such as
      adenovirus latent infection to the airways.

PMID- 14674317
TI  - [The environmental risk factors for COPD--tobacco smoke, air pollution,
      chemicals].
AB  - The identification of risk factors is an important step toward developing
      strategies for prevention and treatment of any disease. The risks of COPD are
      related to environmental exposures in combination with the genetic makeup of the
      individual. The principal environmental factor in COPD is well known--exposure to
      cigarette smoke--and it can be modified. However, although smoking is the best
      studied COPD risk factor, it is not only one. Air pollution, occupational dusts
      and chemicals can also cause COPD when the exposures are sufficiently intense or
      prolonged. This is a summary of environmental risk factors for COPD.

PMID- 14674318
TI  - [Role of inflammatory cells in the development of airway inflammation].
AB  - Chronic obstructive pulmonary disease(COPD) is a chronic airway disorder
      characterized by obstructive airflow limitation which is not completely
      reversible with treatment. Inflammatory changes in the peripheral airways,
      especially those with the diameter less than 2 mm(so-called small airway disease)
      have been speculated to be initial steps of COPD. However, it remains unclear
      which types of the cells play an essential role in the pathogenesis of these
      lesions. Studies with bronchoalveolar lavage demonstrated an increase in
      neutrophil numbers and the neutrophil chemoattractant interleukin-8. Tobacco
      smoke-induced IL-8 expression in the airway epithelial cells and macrophages
      results in neutrophil accumulation and activation. Immunohistochemical analysis
      recently demonstrated that T lymphocytes, especially CD8(+) cells are increased
      in the pathologic lesions. However, their role in the pathogenesis of
      inflammatory changes remains unelucidated. Further studies are necessary for the
      new development of treatment for this progressive lung disease.

PMID- 14674319
TI  - [Proteases involved in airway inflammation of COPD].
AB  - Chronic obstructive pulmonary disease(COPD) is one of major cause of morbidity
      and mortality worldwide. Cigarette smoking is the main risk factor for the
      development of COPD and causes airway inflammation and parenchymal destruction.
      In the pathogenesis of COPD, protease-antiprotease imbalance is considered to be
      one of the important processes through the study of alpha 1-antitrypsin
      deficiency. At present, not only neutrophil elastase but also cathepsin and
      matrix metalloproteinases produced by inflammatory cells are demonstrated to be
      important in the pathogenesis of COPD, In this review, the roles of various kinds
      of proteases in the airway inflammation are summarized.

PMID- 14674320
TI  - [Implication of oxidant stress in airway inflammation].
AB  - There are many species of oxygen radicals in the environment. Inflammatory cells
      also produce many oxidants in biological tissues. The lung is constantly exposed
      to highest content of oxygen in the body, and frequently exposed to tobacco
      smoke, industrially polluted air, and exhausted gas. These conditions make the
      airway to be exposed to oxygen radicals, and may lead to subsequent oxidant
      stress and tissue injury, when the stress overwhelms the antioxidant system.
      Oxidants may also regulate expression of several proinflammatory cytokines with
      interacting with transcription factors. There is increasing evidence that COPD is
      related to airway oxidant stress. Measurement of some exhaled gas contents may be
      useful to monitor ongoing inflammation/oxidant stress and subsequent lipid
      peroxidation in COPD.

PMID- 14674321
TI  - [Apoptosis in chronic obstructive pulmonary disease].
AB  - Although the major sites of airflow limitation in patients with COPD are most
      likely the peripheral airways, lesions in both the peripheral airways and the
      lung parenchyma contribute to chronic airflow limitations. Abnormalities in the
      lung parenchyma is recognized as emphysema characterized by air space enlargement
      and alveolar destruction. The mechanism responsible for the development of
      emphysema was thought to be protease/antiprotease imbalance and oxidative stress.
      A very recent study shows that alveolar cell apoptosis causes lung destruction
      and emphysematous changes. Thus, apoptosis may play a significant role in the
      development of emphysema.

PMID- 14674322
TI  - [The mechanism of airway obstruction in the development of COPD].
AB  - Cigarette smoking is the major cause of chronic obstructive pulmonary disease
      (COPD) and it is generally accepted that proteinases released from neutrophils
      and/or macrophages are involved in the development of emphysema. It remained
      unknown why only a small portion of smokers develops clinically apparent
      emphysema and which cells and/or proteinases play a key role in the pathogenesis
      of COPD. Structural cells in the lungs such as epithelial cells and endothelial
      cells may also be involved in cell death and repair. Individual genetic
      background may regulate the function of these cells in response to cigarette
      smoke and is related to the susceptibility to pulmonary emphysema.

PMID- 14674323
TI  - [Pulmonary hypertension and cor pulmonale in COPD].
AB  - The prevalence and natural history of cor pulmonale in COPD are not yet clear.
      Factors that are known to contribute to the development of pulmonary hypertension
      in COPD include hypoxic pulmonary vasoconstriction(HPV), remodeling of pulmonary
      arteries, destruction of the pulmonary capillary bed and polycythemia. In
      addition, impaired mechanisms of endothelium-dependent vasodilation such as
      reduced NO synthesis or release, and abnormal secretion of vasoconstrictor
      peptides play an important role in the development of pulmonary hypertension.
      These factors can lead to right ventricular hypertrophy and right heart failure.
      Pulmonary hypertension develops late in the course of COPD (stage III) usually
      after the development of severe hypoxemia and is associated with a poor prognosis
      of the disease.

PMID- 14674324
TI  - [Recent advances in computed tomography as a diagnostic tool for COPD].
AB  - The diagnosis of chronic obstructive pulmonary disease(CODP) has been mainly
      based on the physiologic impairment(obstructive ventilatory disturbance).
      However, recent advances in computed tomography including high resolution,
      helical and multi-detector CTs have made it possible to diagnose patients with
      CODP morphologically by identifying low attenuation areas on CT. In addition,
      airway dimensions including luminal area and airway wall thickness have been
      measurable. CT is now an useful tool for exploring not only parenchymal but also
      airway abnormality in COPD. These progresses in CT could contribute to elucidate
      the etiology of COPD, divide COPD patients into two groups, emphysema-dominant
      and airway disease-dominant patients, and treat them separately.

PMID- 14674325
TI  - [Lung function test for COPD].
AB  - According to the guideline presented by Global Initiative for Chronic Obstructive
      Lung Disease(GOLD), the diagnosis of chronic obstructive pulmonary disease (COPD)
      has been simplified. COPD is diagnosed when FEV1(forced expiratory volume in one
      second)/FVC(forced vital capacity) is less than 70% (except Stage 0), and also
      the severity of disease is classified by FEV1. In this article, spirometry, a
      screening test for COPD, is explained at first, and then further examination to
      understand the pathophysiology of COPD is discussed. For management and following
      up of COPD, both lung function test and arterial blood gas analysis are
      important.

PMID- 14674326
TI  - [Diagnostic use of bronchoscopy and bronchial biopsies in chronic obstructive
      pulmonary disease].
AB  - Studies examining the bronchial biopsy specimens taken from patients with chronic
      obstructive pulmonary disease(COPD) have shown that there is an inflammatory
      condition in which CD8+ T-lymphocytes and macrophages are predominated by using
      immunohistochemical staining. Although neutrophils are scanty in the airway wall,
      but are increased in the airway lumen. CD8+ cells exhibit a extensive
      distribution along the subepithelial zone of the airways. The number of CD8+
      cells showed a significant negative correlation with FEV1 percentage of
      predicted. Patients with COPD examined during a mild exacerbation of the disease
      showed a prominent eosinophilia both in the airway wall and in the airway lumen.
      Studies of the bronchial biopsy have been provided more adequately information
      about the cellular and structural bases of COPD.

PMID- 14674327
TI  - [Management of patients with stable COPD].
AB  - Management of patients with stable COPD is consisted with education for smoking
      cessation, pharmacologic therapy and non-pharmacologic therapy. Smoking cessation
      is a basic standing point for management of COPD. Prognosis of COPD with less
      economical cost is improved by smoking cessation. Pharmacotherapy should be
      arranged according to the severity of disease. beta 2 agonists, anticholinergic
      agents, theophylline and a combination of one or more of these drugs are
      available to improve obstructive ventilatory impairment. Inhaled steroid is used
      for patients with asthmatic symptom and with documented spirometric response to
      steroid. Pulmonary rehabilitation is useful for patients with all severity to
      reduce symptoms and to improve quality of life. Selected patients can take
      beneficial effect by long-term oxygen therapy, ventilatory support and surgical
      treatment.

PMID- 14674329
TI  - [New drug therapy of chronic obstructive pulmonary disease].
AB  - The progression of chronic obstructive pulmonary disease(COPD) can be inhibited
      by smoking cessation. As adjunct drugs, nicotine replacement therapy and an
      antidepressant bupropion are found to improve the abstinence rate from smoking.
      The mainstay of drug therapy of COPD consists of bronchodilators. Inhaled long
      acting anticholinergic agents are in development. Inhaled long-acting beta 2
      agonists are newly available. Theophylline has weak antiinflammatory effects. The
      significance of corticosteroids and mucolytic drugs in stable COPD is yet to be
      elucidated. In severely hypoxemic patients with COPD long-term domicillary oxygen
      therapy improves the survival rate. There is no drug therapy which can prevent
      the long-term deterioration of pulmonary function in patients with COPD. New
      class of drugs are now in development.

PMID- 14674328
TI  - [Administration of acute exacerbation of chronic obstructive pulmonary disease].
AB  - We have to consider the exacerbation of chronic obstructive pulmonary
      disease(COPD) may be caused not only by infection, but also by acute exacerbation
      of chronic heart failure, pulmonary embolism, pneumothorax, or other
      cardiopulmonary complications. Because it is characteristic that the exacerbation
      of COPD is often recurensive, the most important thing is the administration
      during stable status. Approximately 40% of pathogens of the acute infectious
      exacerbation of COPD are Haemophilus influenzae, Streptococcus pneumoniae,
      Moraxella catarrhalis, Pseudomonas aeruginosa, Staphylococcus aureus, and
      Echelisia coli. Also, approximately 15% is exacerbated by atypical pathogens such
      as Chlamydia pneumoniae and approximately 30% is by viral infection. We should
      contemplate the possibility of pathogens according to the statistics, when we
      choose antibiotics empirically.

PMID- 14674331
TI  - [Efficacy of pulmonary rehabilitation and clinical practice].
AB  - Pulmonary rehabilitation(PR) is comprehensive care for patients with chronic
      pulmonary disorder, especially chronic obstructive pulmonary disease. PR is done
      by team approach and individualized according to the patient's goal. The
      important components of PR are assessment, patient education, exercise,
      psychosocial support and follow-up. Patient education includes understanding of
      pathophysiology of patient's own lung disease, breathing retraining, bronchial
      hygiene, smoking cessation, medications, nutrition and prevention of acute
      exacerbation. The role of exercise training is most important and its efficacy
      has been strongly supported. Exercise training program should include both lower
      and upper extremity training, and in selected patients ventilatory muscle
      training is recommended. PR improves exercise tolerance, dyspnea, health-related
      QOL. Follow-up care is needed for long-term benefits.

PMID- 14674330
TI  - [Corticosteroids for treatment of patients with chronic obstructive pulmonary
      disease].
AB  - There is scientific evidence that corticosteroids should be given in exacerbation
      of COPD. It is still controversial if patients with stable COPD could receive
      benefits by long-term administration with inhaled corticosteroids. However, many
      investigators recently consider favorable opinions for inhaled corticosteroids,
      since inhaled corticosteroids could decrease the frequency of exacerbation
      especially in severe to moderate COPD.

PMID- 14674332
TI  - [The indication and practice of home oxygen therapy].
AB  - COPD(Chronic Obstructive Pulmonary Disease) is a cause of chronic respiratory
      failure which leads to pulmonary hypertension and cor pulmonale. Not only chronic
      hypoxia but also low QOL(quality of life) due to dyspnea are shown to affect
      survival of COPD patients. HOT(Home Oxygen Therapy) is one of the most successful
      home therapy in Japan after the availability of health insurance in 1985. HOT is
      the only therapy to prolong life expectancy of COPD patients with chronic
      respiratory failure. The induction of HOT needs a consideration of risk of
      narcosis and evaluations of oxygen desaturation during exercise and sleep as well
      as hypoxia at rest. Higher QOL of HOT patients might require an alteration of
      prescription guidelines of HOT.

PMID- 14674333
TI  - [Long-term outcomes and possibility of LVRS].
AB  - A variety of surgical procedures for emphysema have been designed in the past.
      LVRS has recently been rediscovered and offers the potential of improving not
      only the pulmonary function but also quality of life of patients with advanced
      emphysema. Many studies have demonstrated short-term improvement in dyspnea and
      exercise tolerance following LVRS. But it is still unknown that the long-term
      effects of LVRS remain. We showed the data with undergone our LVRS and on the
      basis of newest NETT report. Our overall survival rate at 2 years, 4 years and 6
      years was 81.5%, 61.1% and 56%, respectively, with LVRS. Survival advantage was
      observed the patient with predominantly upper lobe. Patients with preoperative%
      FEV1 of less than 30 showed a 51.5% survival rate 5 years after LVRS. In
      contrast, patients with preoperative FEV1 greater than 30%, 76.2% survived 5
      years(p < 0.05). There was not significant but it was suggested that smoking
      history may affect the survival rate after LVRS.

PMID- 14674334
TI  - [Indication and recipient selection for lung transplantation].
AB  - Lung Transplantation has become an established therapeutic modality for selected
      patients with end-stage lung diseases including chronic obstructive lung
      disease(COPD). Candidates for lung transplantation should have chronic disease
      for which no further medical or surgical therapy is available and survival is
      limited. Disease specific guidelines of lung transplant candidates for COPD
      patients include FEV1.0 < 25% of predicted, PaCO2 > 55 Torr or cor pulmonale. As
      of August 2003, 13 cadaveric lung transplantation and 31 living-donor lobar
      transplantation has been performed in Japan, and 38 of 44 recipients are alive.
      The shortage of cadaveric donors, infection and chronic rejection are the major
      problems in lung transplantation and every endeavor must be made to solve them.

PMID- 14674335
TI  - [End of life care for patients with COPD].
AB  - Chronic obstructive pulmonary disease(COPD) is a common cause of morbidity and
      mortality. It currently fourth leading cause of death in world wide and
      importance for end of life care for end-stage patients with COPD is increasing.
      Patients with COPD experience acute exacerbation once disease progressed. Once
      patients with COPD admitted to the hospital by acute exacerbation, prognosis of
      these patients is poor and these patients should be considered as an end-stage
      COPD. When compared with advanced lung cancer patients, patients with COPD have
      more deterioration of quality of life, more symptoms such as despnea, general
      fatigue, appetiteloss, anxiety, and deterioration of activities of daily living.
      However, these patients with COPD are more treated with life sustained
      interventions, palliation for these symptoms are not sufficients. In caring
      patients with severe COPD, consideration should be given to implementing
      palliative treatments more aggressively. In order to improve end of life care for
      patients with advanced COPD, it is also important to establish local support
      system for caring these patients.

PMID- 14674336
TI  - [Retinoic acid and regeneration therapy of the lung diseases].
AB  - Retinoic acid is the bioactive metabolite of vitamin A and considerable evidence
      implicates retinoic acid as important signaling molecule during normal lung
      development and retinoid signaling elements, such as receptors and binding
      proteins have been described in the developing lung. Alveolization, or the
      formation of alveoli during lung development, is essentially completed in the
      neonatal period, and little neo-alveolization occurs in the adult lung. Recently,
      several studies have shown that retinoic acid is effective in promoting
      alveolization in neonatal rats, in adult rats with elastase-induced emphysema.
      However, the exact mechanism governing this regeneration is still unknown. Recent
      advanced technologies will clarify the role of retinoic acid in alveolization and
      even how alveolization occurs, leading to regeneration therapy for the
      devastating lung diseases, such as emphysema and fibrotic disorders.

PMID- 14674337
TI  - [Basic policy towards patient's violation of drug control law].
AB  - All medical workers have a duty to protect a patient's privacy by law. Civil
      servants have a duty to prosecute anyone if a crime has been committed and others
      have the right to prosecute. When medical workers find their patient using
      illegal drugs, they are in a situation where any possible action they take is
      either a breach of one of the duties or an abandonment of the right to prosecute.
      Any worker in this situation should choose to do what will greater benefit
      society. Medical workers should avoid prosecuting a patient for illegal drug use,
      so that drug users can seek help. At the same time medical workers should try to
      put the patient in a situation where the patient's drug use in the future can be
      treated by the criminal justice system.

PMID- 14674338
TI  - The first step toward the future of family medicine.

PMID- 14674339
TI  - Evaluating online EBM.

PMID- 14674340
TI  - Clarifying EBM resources.

PMID- 14674341
TI  - The root of the problem.

PMID- 14674342
TI  - How to opt out of Medicare.

PMID- 14674343
TI  - The Stark truth about the Stark law. Part I.

PMID- 14674344
TI  - How to boost your bottom line with an office procedure.

PMID- 14674345
TI  - Family medicine takes center stage.

PMID- 14674346
TI  - When your patients are in mourning.

PMID- 14674347
TI  - An asymmetric, oligoarticular, seronegative, inflammatory arthritis.

PMID- 14674348
TI  - The chivalrous physician.

PMID- 14674349
TI  - [New capacities of roentgen diagnosis in detecting small intestinal pathology].
AB  - The paper based on the data of more than 200 studies of the small bowel with the
      new agent Entero-VU specially designed for X-ray study of the bowel gives an
      objective evaluation of this agent. The authors of the paper analyze the
      capacities of Entero-VU in diagnosing 38 cases of Crohn's disease, tuberculosis
      and tumors of the small bowel. Moreover, as a separate section the paper provides
      an assessment of the agent in mapping the X-ray standards of the small bowel. In
      the authors' opinion, the use of this agent as though fills the existing gap in
      the X-ray study of the small bowel.

PMID- 14674350
TI  - [Results of point stenting of extended coronary stenoses in patients with
      ischemic heart disease].
AB  - The paper analyzes the immediate and long-term results of point stenting in
      patients with extended (more than 30 mm) coronary stenoses and compares them with
      those obtained by routine stenting. The study included 177 patients with varying
      extent stenoses who underwent traditional implantation of intracoronary stents.
      Thirty-seven patients undergone the so-called point stenting formed a separate
      group. There was no significant difference in clinical and angiographic success
      rates between the patients of all three groups. Significant difference was also
      absent in subacute stent thrombosis between the patients of Groups 2 and 3 and
      those of the point stenting group. Thus, acute or subacute stent thrombosis was
      noted in 4 (2.3%) patients from the routine stenting groups, all the patients
      being from Groups 2 and 3, and in 2 (5.4%) from the point stenting group. No
      significant difference was found in the incidence of recurrent angina pectoris
      (restenosis) between Groups 1 and 2 and between Groups 2 and 3. At the same time,
      recurrent angina (restenosis) significantly more frequently developed in the
      patients of Group 3 than those of Group 1. As compared with Groups 2 and 3
      patients, there was no significant difference in the incidence of recurrent
      angina (restenosis).

PMID- 14674351
TI  - [X-ray manifestations of congenital deformities of the visceral cranium].
AB  - The paper discusses the most rational algorithm of an X-ray study and its results
      obtained while analyzing X-ray findings in 320 patients with severe congenital
      deformities of the visceral cranium. The malformations are shown to involve not
      only the visceral cranium, but also the cerebral cranium and its base and they
      can be rarely assigned to any of the known syndromes as they have frequently
      something in common. The most rational scheme of a X-ray study is presented.

PMID- 14674353
TI  - [MRI in shoulder joint instability].
AB  - The paper provides the results of MRI studies in 100 patients having complaints
      of pain and impaired movements in the shoulder joint in order to establish a
      diagnosis. Sixty-three patients were found to have MRI signs of shoulder joint
      instability (SJI). The paper presents and states the found MRI symptoms of SJI.
      The author concludes that MRI of the shoulder joint in its instability should be
      used appropriately as it may early reveal changes in the articular osseous,
      cartilaginous, and soft tissues, which is useful in diagnosing and choosing a
      treatment.

PMID- 14674352
TI  - [Examining the effect of amiodarone on the lung: data of prospective study].
AB  - Amiodarone (A) that belongs to Class III antiarrhythmics is a highly
      antiarrhythmic agents not only in treating, but in preventing various cardiac
      arrhythmias. However, its prolonged treatment may have an adverse life
      threatening effect on the lung in 1-10% of patients. The purpose of our study was
      to verify the safe effect of A on the lung. Forty-one patients receiving A were
      examined in the period of its saturation and for the following 6 months. A
      hundred and forty-nine patients treated with its maintaining doses long (for 11
      years) were also studied. Lung X-ray films and spirograms were repeated every 1-3
      months at the beginning of therapy and then every 6 months. Side pulmonary
      effects were not observed. The findings may lead to the conclusion that
      comparatively small maintaining doses of A are safe for the patient.

PMID- 14674354
TI  - [Systems analysis of X-ray films of the vertebral column].
AB  - The systems analysis of spinal X-ray films (SASXF) developed by the author solves
      the problem of an integral and, concurrently, detailed study of the spine of a
      patient on the basis of routine X-ray study. The examination of the patient gave
      rise to a patient's systems spinal model that considers the individual features
      of the vertebral column, which are most significant for a manual therapist's
      work. The standards of a X-ray study, a protocol form, and examination tools are
      described. An example of systems spinal model is given. The experience
      accumulated during studies of more than 2000 patients has shown that this
      procedure is highly effective in implementing medical manipulations by the
      methods of manual therapy.

PMID- 14674355
TI  - [Spiral computed tomography in the diagnosis of limb osteomyelitis].
AB  - The results of radiation studies in 121 patients of different age (4 to 75 years)
      examined for limb osteomyelitis are analyzed. All the patients underwent routine
      X-ray study and computed tomography (CT), 26 patients had X-ray fistulography; 8,
      linear tomography; 10, CT fistulography; 6, scintigraphy, and 15, ultrasound
      study. Acute hematogenous osteomyelitis (AHO), chronic hematogenous osteomyelitis
      (CHO), and atypical (here Garre's sclerosing osteomyelitis and Brodie's abscess)
      osteomyelitis were ascertained in 10.6, 26.4, and 10.1% of cases, respectively.
      Posttraumatic osteomyelitis was diagnosed in almost 50% of the patients. CT
      defined the phase of chronic limb osteomyelitis. Spiral CT has proven to be the
      most effective technique for diagnosing limb osteomyelitis as compared with
      routine X-ray study: the accuracy of X-ray study was 81.8%, its sensitivity,
      84.9%, and specificity, 60.0% and those of computed tomography were 96.7, 99.1,
      and 80.0%, respectively.

PMID- 14674356
TI  - [Bronchioalveolar cancer : a case report].

PMID- 14674357
TI  - [Diverticulum of the cardia].

PMID- 14674358
TI  - [Intrathoracic and intraabdominal splenosis following 40 years after
      splenectomy].

PMID- 14674359
TI  - [To the quality of a medical X-ray film. Fujifilm].

PMID- 14674360
TI  - [Prospects of the use of non-ionic X-ray contrast substances during endoscopic
      retrograde cholangiopancreatography].

PMID- 14674361
TI  - Community groups push for a greater role in stemming epidemic. Barriers,
      including lack of funding, still exist.
AB  - Minority AIDS groups, such as the National Minority AIDS Council and a number of
      community-based organizations have been working to bring HIV/AIDS issues to the
      attention of legislators in hopes of influencing future budget decisions. Their
      recent lobbying efforts are fueled by the fact that HIV and AIDS
      disproportionately impact African-American and Latino communities, resulting in
      some dying from AIDS before they even start antiretroviral treatment.

PMID- 14674362
TI  - Multiple challenges await long-term survivors. They cope through helping others.

PMID- 14674363
TI  - Multiple barriers prevent minorities' early treatment. AIDS stigma, lack of
      transportation top list.
AB  - The most recent statistics show that HIV is the leading cause of death for young
      African-Americans and the third leading cause of death for both African-Americans
      and Latinos in the 35-44 age group. A Centers for Disease Control and Prevention
      study found that African-Americans and Latinos were more likely to be tested late
      for HIV than were whites. In addition, previous research has shown that HIV
      infected African-Americans and Latinos are more likely to be uninsured, to have
      not received antiretroviral drugs, to lack transportation for visiting doctors,
      and to have had recent hospitalizations.

PMID- 14674364
TI  - Are former Soviet nations plodding down wrong path? Experts lack optimism for the
      region.
AB  - Researchers are concerned that the current injection drug use epidemic in former
      Soviet Union countries is being handled in a way that could lead to further
      explosions of the HIV epidemic.

PMID- 14674365
TI  - Bush administration backs out of global AIDS funding. International AIDS goals
      are unmet, report says.
AB  - AIDS activists are beginning to become disillusioned with the Bush
      administration's commitment to fully funding international AIDS prevention and
      treatment.

PMID- 14674366
TI  - New research offers clues to HIV/HCV co-infection. One study also finds diabetes
      link.
AB  - Several new studies presented at ICAAC have shown how HIV patients who are co
      infected with hepatitis C are at greater risk for medical complications,
      including diabetes.

PMID- 14674367
TI  - HIV resistance patterns are shifting, study shows. Regression model could aid
      clinicians.
AB  - Investigators studying genotypes of 64,000 clinical samples submitted for
      genotyping have found that HIV-1 drug resistance remains extensive, but that
      trends have shifted in recent years.

PMID- 14674368
TI  - Drug resistance guide being pondered by CDC. As HIV drug resistance rises,
      surveillance needed.
AB  - Guidelines released by two groups this year recommend resistance testing for all
      recently infected patients beginning treatment. However, both groups also suggest
      considering resistance testing for drug-naive patients whose infections are not
      recent, particularly if the prevalence of resistance in the patient's area is 5%
      or greater.

PMID- 14674370
TI  - Biometric surfactant polymers designed for shear-stable endothelialization on
      biomaterials.
AB  - We have developed a series of extracellular matrix (ECM)-like biomimetic
      surfactant polymers to improve endothelial cell adhesion and growth on vascular
      biomaterials. These polymers provide a single-step procedure for modifying the
      surface of existing biomaterials and consist of a poly(vinyl amine) (PVAm)
      backbone with varying ratios of cell-binding peptide (RGD) to carbohydrate
      (maltose), ranging from 100% RGD:0% maltose to 50% RGD:50% maltose. Three
      biomimetic surfaces, as well as a fibronectin (FN)-coated glass surface were
      seeded at confluence with human pulmonary artery endothelial cells (HPAECs) and
      exposed to shear stresses ranging from 0-40.6 dyn/cm2 for periods of 2 h and 6 h.
      Surfaces were examined for HPAEC coverage and cytoskeletal arrangement as a
      function of time and shear stress. In general, after 6 h of shear exposure, EC
      retention on 100% RGD > FN > 75% RGD > 50% RGD. The 100% RGD surface maintained
      more than 50% of its initial EC monolayer at low to moderate shear stresses
      whereas all other surfaces dropped to approximately 40% or less in the same shear
      stress range. The most stable surface, 100% RGD, showed a significant increase in
      cytoskeletal organization at all shear stresses greater than 2.5 dyn/cm2. In
      contrast, there was no real change in cytoskeletal organization on the FN
      surface, and there was a decrease on the 75% RGD surface over time. These results
      indicate that increasing surface peptide density can control EC shear stability.
      Furthermore, improved shear stability increases with increasing peptide density
      and is related to the EC's ability to reorganize its cytoskeleton.

PMID- 14674371
TI  - DDTC, a metabolite of disulfiram, reduces the stimulating effect on ethanol's
      locomotor activity in mice.
AB  - To investigate how diethyldithiocarbamate (DDTC) affects the stimulating effect
      of ethanol on open-field locomotion, mice were pretreated with different doses of
      DDTC 8 hours prior to ethanol. The effect of DDTC and saline on different ethanol
      doses was analyzed. DDTC reduces ethanol-induced locomotor activity in a dose
      dependent manner, not the spontaneous locomotor activity. Aldehyde dehydrogenase
      might influence psychopharmacological effects of ethanol.

PMID- 14674372
TI  - Therapeutic implications of HPA axis abnormalities in Alzheimer's disease: review
      and update.
AB  - The adaptive and maladaptive roles of the hypothalamic-pituitary-adrenal (HPA)
      axis in stressful conditions and in disorders such as major depression,
      posttraumatic stress disorder, and Cushing's syndrome, have been the subject of
      substantial, ongoing study. In particular, HPA disturbances have been associated
      with memory impairments, and hypercortisolemic conditions with atrophy of the
      hippocampus, a limbic structure closely associated with declarative memory.
      Recent discoveries support a more complicated picture of HPA axis function and
      pathology in acquiring, retrieving, and consolidating new memories. These
      findings include: the existence of an 'inverted U-shaped relationship" between
      stimulation of brain glucocorticoid receptors and memory performance; that
      distinct areas of the hippocampus have been found to respond differently to
      cortisol stimulation; and that hippocampal atrophy has been found to be
      potentially reversible in some conditions, although whether such atrophy is a
      cause or effect of these pathological conditions is currently unclear. More
      longitudinal studies of HPA axis function in aging normal individuals, those with
      mild cognitive impairment,and individuals with Alzheimer' disease, examining
      pertinent variables such as APOEe-4 status, are needed to help clarify these new
      findings. Antiglucocorticoid agents appear to have therapeutic value in
      particular conditions. These results are relevant for understanding and treating
      memory dysfunction in individuals with Alzheimer's disease, a disorder
      prominently and invariably characterized by early hippocampal lesions and memory
      impairment. Given the burden of this disease, we feel it timely to encourage
      controlled trials of antiglucocorticoid agents in the treatment of mild cognitive
      impairment and Alzheimers disease.

PMID- 14674373
TI  - Hematopoietic mixed chimerism after allogenic BMT.

PMID- 14674374
TI  - PLT transfusions from D+ blood donors to D-patients with hematologic diseases: am
      update.

PMID- 14674375
TI  - Identification of two new single-nucleotide polymorphisms in FUT3 associated with
      the Lewis-null phenotype.

PMID- 14674376
TI  - Role of the Hct in the treatment of thrombocytopenic patients.

PMID- 14674377
TI  - HBV DNA in plasma pools fractionation.

PMID- 14674378
TI  - Human herpesvirus type 8 among Brazilian blood donors.

PMID- 14674379
TI  - Malignant hypertension presenting as hemolysis, thrombocytopenia, and renal
      failure.
AB  - This case review describes a patient presenting to the emergency department with
      malignant hypertension, a medical emergency occurring in up to 1% of the
      hypertensive population. The features of malignant hypertension resemble those of
      other diseases. For example, the association between red-cell fragmentation and
      malignant hypertension is thought to be due to endothelial injury and fibrinoid
      necrosis, which promote hemolysis, platelet destruction, and varying degrees of
      renal failure, resulting in a clinical picture similar to that of thrombotic
      thrombocytopenic purpura. Resolving the hemolysis and improving the renal
      function can only be achieved through rapid and effective control of the blood
      pressure. Without treatment, the survival rate for malignant hypertension is 10%
      to 35%. With appropriate treatment, the 5-year survival rate is 75%.

PMID- 14674381
TI  - Intima-media thickness side differences are limited to the common carotid artery.

PMID- 14674384
TI  - Fish are here to stay.

PMID- 14674385
TI  - Home, green home.

PMID- 14674386
TI  - Building a better brick.

PMID- 14674387
TI  - Public opinion in a crisis.

PMID- 14674388
TI  - Shareholders speak up.

PMID- 14674389
TI  - PILGrimage to New York.

PMID- 14674391
TI  - Firefighter findings.

PMID- 14674393
TI  - Insult to newborn immunity.

PMID- 14674394
TI  - Making sense of a family history of polyps.

PMID- 14674395
TI  - Flavonoids in food.

PMID- 14674396
TI  - National Institutes of Health Center Grants. Final rule.
AB  - The National Institutes of Health (NIH) is amending its regulations governing
      center grants to reflect their applicability to several new grant programs,
      including research on autism, Alzheimer's disease, fragile X disease, and
      minority health disparities and other types of health disparities.

PMID- 14674398
TI  - Medicare program; Medicare prescription drug discount card. Interim final rule
      with comment period.
AB  - Section 101, subpart 4 of the Medicare Prescription Drug, Improvement, and
      Modernization Act of 2003, codified in section 1860D-31 of the Social Security
      Act, provides for a voluntary prescription drug discount card program for
      Medicare beneficiaries entitled to benefits, or enrolled, under Part A or
      enrolled under Part B, excluding beneficiaries entitled to medical assistance for
      outpatient prescription drugs under Medicaid, including section 1115 waiver
      demonstrations. Eligible beneficiaries may access negotiated prices on
      prescription drugs by enrolling in drug discount card programs offered by
      Medicare-endorsed sponsors. Eligible beneficiaries may enroll in the Medicare
      drug discount card program beginning no later than 6 months after the date of
      enactment of the Medicare Prescription Drug, Improvement, and Modernization Act
      of 2003 and ending December 31, 2005. After December 31, 2005, beneficiaries
      enrolled in the program may continue to use their drug discount card during a
      short transition period beginning January 1, 2006 and ending upon the effective
      date of a beneficiary's outpatient drug coverage under Medicare Part D, but no
      later than the last day of the initial open enrollment period under Part D.
      Beneficiaries with incomes no more than 135 percent of the poverty line
      applicable to their family size who do not have outpatient prescription drug
      coverage under certain programs--Medicaid, certain health insurance coverage or
      group health insurance (such as retiree coverage), TRICARE, and Federal employees
      Health Benefits Program (FEHBP)--also are eligible for transitional assistance,
      or payment of $600 in 2004 and up to $600 in 2005 of the cost of covered discount
      card drugs obtained under the program. In most cases, any transitional assistance
      remaining available to a beneficiary on December 31, 2004 may be rolled over to
      2005 and applied toward the cost of covered discount card drugs obtained under
      the program during 2005. Similarly, in most cases, any transitional assistance
      remaining available to a beneficiary on December 31, 2005 may be applied toward
      the cost of covered discount card drugs obtained under the program during the
      transition period. The Centers for Medicare & Medicaid Services will solicit
      applications from entities seeking to offer beneficiaries negotiated prices on
      covered discount card drugs. Those meeting the requirements described in the
      authorizing statute and this rule, including administration of transitional
      assistance, will be permitted to offer a Medicare-endorsed drug discount card
      program to eligible beneficiaries. Endorsed sponsors may charge beneficiaries
      enrolling in their endorsed programs an annual enrollment fee for 2004 and 2005
      of no more than $30; CMS will pay this fee on behalf of enrollees entitled to
      transitional assistance. To ensure that eligible Medicare beneficiaries take full
      advantage of the Medicare drug discount card program and make informed choices,
      CMS will educate beneficiaries about the existence and features of the program
      and the availability of transitional assistance for certain low-income
      beneficiaries; and publicize information that will allow Medicare beneficiaries
      to compare the various Medicare-endorsed drug discount card programs.

PMID- 14674400
TI  - [Medicine: art or science?].
AB  - The question of how science, medicine and medical practice are related also
      compromises the crucial issue of the character of medicine. At the beginning of
      the 19th century, medicine tried to overcome the ancient contradiction within the
      unity of scientific thought and the deduction of guidelines and techniques for
      medical practice. This aim was partly achieved in medico-theoretical reasoning
      and practical procedures as well as for nosology, casuistic thinking and
      diagnostics. But medicine is a discipline directed towards healing. So the
      intentions of medicine and the reality of clinical healing possibilities,
      however, showed an increasing divergence since the middle of the 19th century.
      This divergence triggered considerable reactions not only from "Schulmedizin" and
      from other disciplines but also from practicing doctors and mainly from
      (disappointed) patients. Together with the continuous changes in empirical
      clinical research these internal and especially external reactions to medicine
      showed fundamental differences between medicine and the sciences. During the
      decades of this development it has become obvious that medicine will never become
      a pure science, not even an applied science. As medicine is concerned with
      patients who need to be considered as individual subjects, medical knowledge and
      medical practice consequently form a dialectic unity which is directed by the
      patient as a subject.

PMID- 14674401
TI  - Comment: assessment of an age-adjusted warfarin initiation protocol.

PMID- 14674402
TI  - ["Perfect virtue": a cross-cultural study of health care in Europe and China].
AB  - For the past 2.500 years, the civilizations of Europe and China have integrated
      heterogeneous therapeutic systems. This paper discusses the circumstances that
      account for a) basic paradigmatic changes in health care and b) acceptance of
      mutually antagonistic health care systems within one society. A survey of
      European and Chinese medical history suggests that conceptualizations of disease
      and health, prevention and therapy, reflect the political and socio-economic
      environment affecting a given social group. As emerging concepts of threats,
      defenses and treatments relating to the social organism arise, they are projected
      onto the human organism and give rise to new notions of disease. While there are
      always those who insist on the exclusive validity of a specific theory or
      treatment, such claims have never been realistic. Both in Europe and in China,
      most people patronize various treatments, which rest on different and even
      contradictory conceptualizations of the organism, health and therapy.

PMID- 14674403
TI  - Comment: electrocardiographic and cardiovascular effects of the 5
      hydroxytryptamine-3 receptor antagonists.

PMID- 14674404
TI  - [Syphilis, medicine and morality].
AB  - This paper analyzes the relation between sin, punishment and syphilis during the
      19th and 20th centuries. Examination of preventive and therapeutic strategies for
      venereal infection shows that the deep-rooted connection between conceptions of
      sin, punishment and venereal disease has lasted well into the 20th century.

PMID- 14674405
TI  - [Concepts of success in the treatment of tuberculosis in the early 20th century].
AB  - This paper deals with the social construction of medical success in various
      therapies used to treat tuberculosis during the first half of the 20th Century.
      The three main therapies discussed-Tuberculin treatment, sanatorium therapy and
      chest surgery-show distinctly different success patterns. For example, the
      success of sanatorium treatment was evaluated differently during and after
      treatment: during treatment, quantifiable data such as weight and body
      temperature were seen as indicators of health. After discharge, however, success
      was defined as long-term survival. On the other hand, when chest surgery was
      used, success meant simply that patient was able to survive the surgery itself
      long-term effects and patient's survival after discharge were not addressed. Such
      comparisons illustrate that the definition of medical success rested as much on
      the dismissal of negative data as on positive empirical results.

PMID- 14674406
TI  - Methicillin-resistant Staphylococcus aureus infections among competitive sports
      participants - Colorado, Indiana, Pennsylvania, and Los Angeles County, 2000
      2003.

PMID- 14674407
TI  - [Medical claims and women's experience. Physician-performed abortions in the
      Weimar Republic].
AB  - The campaign for abortion reform in the Weimar Republic occasioned passionate
      disputes between factions supporting and opposing liberalization of abortion
      laws. Nevertheless, both camps agreed on one issue: that doctors, and only
      doctors, should be authorized to terminate a pregnancy. The implication was that
      an operation induced by a registered medical practitioner was safe, while so
      called back-street operations were always dangerous. By and large, this view has
      also been accepted by historians, often uncritically. This article shows that
      evidence of the very real risks of terminating a pregnancy was open to cultural
      and political manipulation. The claims of academic physicians were often
      contradictory: on the one hand, they dismissed the risks of medical procedures as
      a way of fighting lay abortions; on the other hand, they exaggerated these risks
      as a way of explaining unsuccessful surgeries. Using a case study from Bavaria at
      the beginning of the Republic, this article shows the ambiguous role doctors
      played and the biased view of the courts. It also sheds light on the experience
      of abortion-seeking women, whose interests were largely ignored by the law
      enforcement agencies.

PMID- 14674408
TI  - [The development of modern psychopharmacology. Historical aspects of therapeutic
      claims and capabilities].
AB  - Even though psychopharmacology is an integral part of modern psychiatric
      treatment, it remains a controversial topic in public discourse. Historical
      analysis is an important tool, which gives us a more realistic view of the
      theoretical underpinnings and therapeutic potential of psychopharmacological
      treatments. Not surprisingly, a historical survey of claims and treatments shows
      that psychopharmacological developments are closely connected to the intellectual
      framework of the period. While drugs have been used to treat psychopathological
      disorders since ancient times, post-19th century modern psychopharmacology has
      been characterized by its reliance on science. This study examines this reliance
      on scientific disciplines, such as chemistry and anesthesiology, by examining
      case studies such as the introduction of new psychopharmacological techniques.
      For instance, the introduction in 1869 of the first synthetic sedative, chloral
      hydrate, clearly illustrates several trends in modern psychopharmacology. The
      successful introductions of antipsychotic and antidepressant drugs in the late
      1950s have also been important milestones, which were instrumental in breaking
      down the skepticism of clinical psychiatrists.

PMID- 14674409
TI  - [Hospital treatment: expectations and reality in the 19th century].
AB  - This paper explores the 19th-century evolution in patients' expectations from
      medical treatment in clinics and hospitals. Analysis rests on surveys of hospital
      functions and performance during this period, as well as surveys of patients'
      socio-economic background. The article reveals that the divergence between
      hospital treatment and patients' expectations was not as wide as has been assumed
      until recently. Limited knowledge about 19th century hospitals and clinics, and
      the contemporary conceptualization of hospitals as overwhelmingly efficient
      "health factories" account for this biased evaluation of the past.

PMID- 14674410
TI  - [The art of going hungry. Anorexia in medical texts in the late 19th century].
AB  - The essay analyzes representations of anorexia in French, English and German
      medical literature from 1870 to 1900, paying specific attention to rhetorical
      patterns. Unlike other nervous diseases, anorexia was considered a somatic
      illness. Rather than subjects, patients were regarded simply as skeletal bodies.
      Most medical case histories enact the transformation of an emaciated body into a
      nubile woman-slender, perhaps, but ready for marriage. The patients are described
      as studious girls who 'devour' literature instead of food. This metaphor is taken
      from etiology to therapy, when the so-called "Mastkur" in the sanatorium replaces
      'enormous' amounts of literature with 'enormous' amounts of food to be eaten.

PMID- 14674411
TI  - [Midwives in 18th century Hungary: between tradition and scientific methodology].
AB  - This study concerns midwifery in Hungary in the period 1783-1790, during the
      reign of Joseph II. It is based on annual health reports forwarded to the Council
      of Physicians (Ungarische Statthalterei) and "conduitlists" in table format.
      These narratives and lists illustrate the controversial process of modernization
      in obstetrics and within the community of midwives. Inspired by the
      Enlightenment, Joseph II introduced a series of obstetric reforms. By
      investigating specific cases, this study shows that successful implementation af
      these reforms depended largely on the physicians themselves: their dedication,
      efficacy, and ability to communicate with the midwives they supervised. While
      interpreting the conflicts triggered by the reforms, this study also considers
      the economic and social conditions at large, such as the centuries-old
      coexistence of several religions and nationalities that characterized Hungary
      during this period.

PMID- 14674412
TI  - ["My contribution to humanity". The work of the Prussian lay physician Arthur
      Lutze (1813-1870)].
AB  - The aim of this paper is to describe the life and work of the homeopathic lay
      physician Arthur Lutze (1813-1870), particularly his work in Prussia. The paper
      also helps explain the extraordinary popularity of non-medical practitioners
      during this period. Lutze's years in Prussia were fundamental for his homeopathic
      ambitions, since they afforded him access to many of the renowned homeopaths of
      the period. Lutze gained popularity by focusing his practice on the common
      people. Even though he was not licensed and he collaborated with unknown non
      medical practitioners, Lutze gained legitimacy through the work of properly
      certified doctors.

PMID- 14674413
TI  - [The First School of Vienna and Samuel Hahnemann's pharmaceutical techniques].
AB  - The First or Elder Vienna School of Medicine was initiated by Gerard van Swieten,
      the famous pupil of Herman Boerhaave. The aim of this school was to put medicine
      on new scientific foundations-promoting unprejudiced clinical observation,
      botanical and chemical research, and the introduction of simple but powerful
      remedies. One of the products of this school was Anton Storck (1731-1803),
      appointed Director of Austrian public health and medical education by Empress
      Maria Theresia. Following the tradition of the Vienna School, Storck was the
      first scientist to systematically test the effects of so-called poisonous plants
      (e.g., hemlock, henbane, meadow saffron). Discovering new therapeutic properties
      in previously dreaded plants, Storck used himself as a subject in experiments to
      determine tolerable dose levels. As a result of his investigations, Storck was
      able to successfully treat his patients using the drugs he discovered. Samuel
      Hahnemann's later writings, including his "Organon", show that he was
      considerably influenced by Storck's ideas. In fact, Hahnemann's clinical teacher
      at Vienna was a follower of Storck, Joseph Quarin. Hahnemann's elaborate system
      of validating homeopath material can be seen as a development and refinement of
      the techniques he learned in Vienna.

PMID- 14674414
TI  - Undertaker of the mind. John Monro and mad-doctoring in eighteenth-century
      England.

PMID- 14674415
TI  - Local colour: John Dalton and the politics of colour blindness.

PMID- 14674416
TI  - Computed tomography in breast cancer imaging?

PMID- 14674417
TI  - The modern ovary: constructions, meanings, uses.

PMID- 14674418
TI  - Dorsal pancreatectomy with preservation of the ventral pancreas.

PMID- 14674419
TI  - Surgical genomics is here.

PMID- 14674420
TI  - Are cytokines the cause of distant organ injury in acute pancreatitis?

PMID- 14674421
TI  - Theory and practice in nineteenth-century Persian medicine: intellectual and
      institutional reforms.

PMID- 14674422
TI  - More on Darwin's illness.

PMID- 14674423
TI  - Missing links in the history and practice of science: teams, technicians and
      technical work.

PMID- 14674424
TI  - "Purifying" science: E. C. Slater and postwar biochemistry in the Netherlands.

PMID- 14674425
TI  - [Infectious diseases-past, present, future].
AB  - The complex interactions between microorganisms and humans include the well
      known, traditional infectious diseases and also the symbiotic relationship with
      the human endogenous normal flora. Forty years ago everybody was convinced that
      medicine would soon be able to eradicate most of the infectious diseases.
      Perception of victory over infectious diseases has been blunted in recent years
      by nosocomial infections and by the new and re-emerging diseases. The spectrum of
      infectious diseases is expanding and many of those once thought conquered are
      increasing in numbers. Moreover, the problems of infection are present in all
      aspects of medicine and with the field turning more and more complex its
      challenge for practitioners has become increasingly demanding. It is now clear,
      that at the dawn of the new millennium infectious disease remains the number one
      killer in the world.

PMID- 14674428
TI  - [Jesus and healing by faith].

PMID- 14674429
TI  - [Hospital and poor-relief administration in Pest-Buda after the Turkish rule].

PMID- 14674431
TI  - Abstracts of the 27th Scientific Congress of the Germany Society of Hypertension.
      26-29 November 2003, Bonn, Germany.

PMID- 14674430
TI  - Machine vision extracted plant movement for early detection of plant water
      stress.
AB  - A methodology was established for early, non-contact, and quantitative detection
      of plant water stress with machine vision extracted plant features. Top-projected
      canopy area (TPCA) of the plants was extracted from plant images using image
      processing techniques. Water stress induced plant movement was decoupled from
      plant diurnal movement and plant growth using coefficient of relative variation
      of TPCA (CRV[TPCA)] and was found to be an effective marker for water stress
      detection. Threshold value of CRV(TPCA) as an indicator of water stress was
      determined by a parametric approach. The effectiveness of the sensing technique
      was evaluated against the timing of stress detection by an operator. Results of
      this study suggested that plant water stress detection using projected canopy
      area based features of the plants was feasible.

PMID- 14674432
TI  - Circling around the "Vatra": on the Romanian psychogenics of pollution and
      abandonment.

PMID- 14674433
TI  - The hidden city of Kitiezh: trauma and psychogenic arrest in Russia.

PMID- 14674434
TI  - Geometric determinants of directional cell motility revealed using microcontact
      printing.
AB  - Mammalian cells redirect their movement in response to changes in the physical
      properties of their extracellular matrix (ECM) adhesive scaffolds, including
      changes in available substrate area, shape, or flexibility. Yet, little is known
      about the cell's ability to discriminate between different types of spatial
      signals. Here we utilize a soft-lithography-based, microcontact printing
      technology in combination with automated computerized image analysis to explore
      the relationship between ECM geometry and directional motility. When fibroblast
      cells were cultured on fibronectin-coated adhesive islands with the same area
      (900 micrometers2) but different geometric forms (square, triangle, pentagon,
      hexagon, trapezoid, various parallelograms) and aspect ratios, cells
      preferentially extended new lamellipodia from their corners. In addition, by
      imposing these simple geometric constraints through ECM, cells were directed to
      deposit new fibronectin fibrils in these same corner regions. These data indicate
      that mammalian cells can sense edges within ECM patterns that exhibit a wide
      range of angularity and that they use these spatial cues to guide where they will
      deposit ECM and extend new motile processes during the process of directional
      migration.

PMID- 14674435
TI  - Dysfunctional domesticity: female insanity and family relationships among the
      West Riding poor in the mid-nineteenth century.
AB  - "Dysfunctional domesticity" contributes to the growing reevaluation of the
      importance of the history of the family to understanding the history of insanity.
      Using patient case histories from the West Riding Pauper Lunatic Asylum, this
      article examines representations of family life among poor in England in the
      1830s and 1840s. Among the so-called moral causes of insanity, family
      relationships held a prominent place. Female patients more than male patients had
      their mental illnesses attributed to their domestic circumstances: the poverty of
      their home lives, grief over a death of friends and family, love and marital
      relationships gone wrong, and violence in their homes. The case histories reveal
      that poor women experienced many pressures in the domestic sphere, and insanity
      may have been one way to escape dysfunctional domesticity.

PMID- 14674436
TI  - A matter of privilege: infant mortality in the Garrison Town of Gibraltar, 1870
      1899.
AB  - The British colony of Gibraltar offers an opportunity to compare the infant
      mortality rates of the civilian and military populations inhabiting a small-scale
      urban setting from 1870 to 1899. Both groups shared the same poor-quality
      housing, the same sanitary infrastructure, and the same environmental
      inseparability. Sufficient water supply, in particular, proved to be a daily
      struggle for the families living on the Rock. Privilege for the military meant
      that service families had preferential access to a pure water supply after the
      installation of a water-condensing plant as well as to a better quality supply of
      water and milk. The availability of these privileges to one group, and not the
      other, is associated with a marked decline in infant mortality in the second half
      of the study period.

PMID- 14674437
TI  - Local delivery of matrix metalloproteinase gene prevents the onset of renal
      sclerosis in streptozotocin-induced diabetic mice.
AB  - The present study was undertaken to investigate whether matrix metalloproteinase
      (MMP) functions to prevent the occurrence of destructive fibrosis in progressive
      renal disease. As a sustained release carrier of plasmid DNA, biodegradable
      hydrogels and microspheres were formulated from cationized gelatin prepared
      through aminization. Plasmid DNA was released from the cationized gelatin
      hydrogels as a result of hydrogel degradation. A plasmid DNA including a
      cytomegalovirus promoter and human recombinant MMP-1 gene (pCMV-MMP) was
      constructed. Gelatin microspheres incorporating pCMV-MMP as well as phosphate
      buffered saline (PBS) with or without pCMV-MMP were injected into the renal
      subcapsule of C57BL/6 mice, which were intraperitoneally injected with
      streptozotocin (STZ) to induce diabetes 7 days after operation. The mice were
      killed 4 weeks after STZ injection to sample their blood and kidneys for
      biochemical and histological examinations. An immunofluorescence study confirmed
      that MMP protein was expressed around the renal tissue injected with gelatin
      microspheres incorporating pCMV-MMP. When applied with cationized gelatin
      microspheres incorporating pCMV-MMP, the mice showed a level of blood urea
      nitrogen significantly lower than that of other groups. A reduced content of
      collagen in the kidneys of mice administered gelatin microspheres incorporating
      pCMV-MMP was histologically observed. Further, the hydroxyproline assay revealed
      a significantly decreased content of hydroxyproline in kidney. We conclude that
      sustained release of MMP-1 gene is a promising prophylactic trial for kidney
      fibrolysis and dysfunction in the STZ-induced diabetic mouse model.

PMID- 14674439
TI  - Imperial bedlam: institutions of madness in colonial southwest Nigeria.

PMID- 14674440
TI  - Patrick Browne (ca. 1720-1790), Irish physician, historian and Caribbean
      botanist: a brief biography with an account of his lost medical dissertations.
AB  - Patrick Browne (ca. 1720-1790), a native of County Mayo, Ireland, studied
      medicine in Paris, graduated from the University of Rheims in 1742, and briefly
      continued his studies at Leiden before practising as a doctor at St Thomas's
      Hospital, London. Subsequently, he lived for many years in the Caribbean, in
      Antigua, Jamaica, Saint Croix and Montserrat, but retired to County Mayo in 1771.
      Browne published The civil and natural history of Jamaica in 1756 a most
      significant work in terms of botanical nomenclature, which included new names for
      104 genera, and he promised also a volume of medical essays, but this was never
      printed. Fragments of his essays on venereal disease and yaws have been traced
      among his correspondence with Carl Linnaeus.

PMID- 14674441
TI  - Richard and Emma Stevens and the new photography.
AB  - Richard and Emma Stevens were an enterprising couple from an Indian Army
      background. When they were stationed at Athlone with the Royal Engineers in the
      1890s they visited Birr Castle Observatory and later built their own reflector
      telescope. Less than a year after the publication of Rontgen's discovery of X
      rays, they were producing their own radiographs. Some images and also some of the
      equipment which they used have survived. The couple subsequently returned to
      India where Captain Stevens died in 1900. Emma, possibly the first woman to take
      X-rays, survived into old age and enjoyed a varied and interesting life.

PMID- 14674442
TI  - Collectivity revisited-a reply to Gmel and Rehm.

PMID- 14674443
TI  - [For anterior levator plasty in the treatment of rectoceles in women].

PMID- 14674444
TI  - Succinylmonocholine identified in negative control tissues.

PMID- 14674445
TI  - Microfluidic chip for continuous monitoring of hormone secretion from live cells
      using an electrophoresis-based immunoassay.
AB  - A microfluidic device has been developed for the determination of insulin
      secreted from islets of Langerhans by a capillary electrophoresis competitive
      immunoassay. Online assays were performed by electrophoretically sampling anti
      insulin antibody (Ab), fluorescein isothiocyanate-labeled insulin (FITC-insulin),
      and insulin from separate reservoirs and allowing them to mix as they traveled
      through a 4-cm reaction channel heated to 38 degrees C. From the reaction
      channel, samples were injected onto a 1.5-cm-long electrophoresis channel where
      the FITC-insulin and FITC-insulin-Ab complex were separated in 5 s using an
      electric field of 500 V/cm. Detection limits for insulin were 3 nM in this mode
      of operation. Assays could be collected at 15-s intervals with continuous
      sampling and online mixing for up to 30 min with no intervention. Relative
      standard deviation was 2-6% depending on the insulin concentration. Response time
      to a step change in insulin concentration was 30 s. For live cell monitoring,
      single islets were placed into a reservoir on the chip and fluid in the immediate
      vicinity was continuously sampled to detect insulin secretion from the islet.
      Monitoring of insulin secretion with electropherograms taken at 15-s intervals
      resolved secretory profiles characteristic of first- and second-phase insulin
      secretion. The method should be amenable to other cell or tissue types for
      measurements of release with high temporal resolution.

PMID- 14674446
TI  - Solving the "world-to-chip" interface problem with a microfluidic matrix.
AB  - We report an effective solution to the macroscopic/microfluidic interface issue
      and demonstrate how microfluidics can achieve impressive economies of scale in
      reducing the complexity of pipetting operations. Using an N x N microfluidic
      matrix with N = 20, we performed N2 = 400 distinct PCR reactions with only 2N + 1
      = 41 pipetting steps, compared with the 3N2 = 1200 steps required with
      conventional fluid handling. Each vertex of the matrix has a 3-nL reactor, and a
      single 2-microL aliquot of polymerase is amortized over all 400 independent
      reactions, thus dramatically reducing sample overhead and minimizing reagent
      consumption. Beyond PCR, the matrix chip provides a general method to perform
      chemical and biological experiments with precious reagents in a highly automated
      fashion.

PMID- 14674447
TI  - Dielectrophoresis in microchips containing arrays of insulating posts:
      theoretical and experimental results.
AB  - Dielectrophoresis (DEP), a nonlinear electrokinetic transport mechanism, can be
      used to concentrate and sort cells, viruses, and particles. To date,
      microfabricated DEP-based devices have typically used embedded metal electrodes
      to apply spatially nonuniform, time-varying (AC) electric fields. We have
      developed an alternative method in which arrays of insulating posts in a channel
      of a microchip produce the spatially nonuniform fields needed for DEP. Electrodes
      may be located remotely, allowing operation of the device down to zero frequency
      (DC) without excessive problems of electrolysis. Applying a sufficiently large
      electric field across an insulating-post array produces two flow regimes through
      a competition between electrokinetic flow (combined electrophoresis and
      electroosmosis) and dielectrophoresis. "Streaming DEP" is observed when DEP
      dominates diffusion but is overcome by electrokinetic flow. Particles
      concentrated by DEP forces in areas of electric field extrema travel
      electrokinetically down the array in flowing streams. In an array of posts,
      dielectrophoretic forcing within repeated rows adds coherently to produce flowing
      streams of highly concentrated and rarefied particles. We demonstrate that this
      reinforcement is a strong function of alignment of the array with respect to the
      applied electric field and that the particle concentrations can be "enhanced" or
      "depleted" along columns of posts, enabling a novel class of continuous-flow,
      selective particle filter/concentrator devices. To our knowledge, this is the
      first observation of streaming dielectrophoresis. The second regime is "trapping
      DEP," in which DEP forces dominate over both diffusion and electrokinetic flow,
      reversibly immobilizing particles on the insulating posts, enabling inexpensive
      and embedded batch filter/concentrator devices. Devices can be biased
      electrically to manipulate particles selectively by varying the field strength to
      vary the relative magnitudes of electrokinetic flow and DEP. Post shapes are
      contoured easily to control electric field gradients and, hence, DEP behavior.
      Simple simulations based on similitude of fluid flow and electric field that
      solve the Laplace equation to obtain fluid velocity have also been developed to
      predict the dielectrophoretic behavior in an array of posts. These simulations
      are in excellent agreement with the experimental observations and provide insight
      into electrokinetic behavior to enable design of dielectrophoretic concentrators
      and sorters.

PMID- 14674448
TI  - DNA hybridization and discrimination of single-nucleotide mismatches using chip
      based microbead arrays.
AB  - The development of a chip-based sensor array composed of individually addressable
      agarose microbeads has been demonstrated for the rapid detection of DNA
      oligonucleotides. Here, a "plug and play" approach allows for the simple
      incorporation of various biotinylated DNA capture probes into the bead
      microreactors, which are derivatized in each case with avidin docking sites. The
      DNA capture probe containing microbeads are selectively arranged in micromachined
      cavities localized on silicon wafers. The microcavities possess trans-wafer
      openings, which allow for both fluid flow through the microreactors/analysis
      chambers and optical access to the chemically sensitive microbeads. Collectively,
      these features allow the identification and quantitation of target DNA analytes
      to occur in near real time using fluorescence changes that accompany binding of
      the target sample. The unique three-dimensional microenvironment within the
      agarose bead and the microfluidics capabilities of the chip structure afford a
      fully integrated package that fosters rapid analyses of solutions containing
      complex mixtures of DNA oligomers. These analyses can be completed at room
      temperature through the use of appropriate hybridization buffers. For
      applications requiring analysis of < or = 10(2) different DNA sequences, the
      hybridization times and point mutation selectivity factors exhibited by this bead
      array method exceed in many respects the operational characteristics of the
      commonly utilized planar DNA chip technologies. The power and utility of this
      microbead array DNA detection methodology is demonstrated here for the analysis
      of fluids containing a variety of similar 18-base oligonucleotides. Hybridization
      times on the order of minutes with point mutation selectivity factors greater
      than 10000 and limit of detection values of approximately 10(-13) M are obtained
      readily with this microbead array system.

PMID- 14674449
TI  - Fabrication of histidine-tagged fusion protein arrays for surface plasmon
      resonance imaging studies of protein-protein and protein-DNA interactions.
AB  - The creation and characterization of histidine-tagged fusion protein arrays using
      nitrilotriacetic acid (NTA) capture probes on gold thin films for the study of
      protein-protein and protein-DNA interactions is described. Self-assembled
      monolayers of 11-mercaptoundecylamine were reacted with the heterobifunctional
      linker N-succinimidyl S-acetylthiopropionate (SATP) to create reactive sulfhydryl
      terminated surfaces. NTA capture agents were immobilized by reacting maleimide
      NTA molecules with the sulfhydryl surface. The SATP and NTA attachment chemistry
      was confirmed with Fourier transform infrared reflection absorption spectroscopy.
      Oriented protein arrays were fabricated using a two-step process: (i) patterned
      NTA monolayers were first formed through a single serpentine
      poly(dimethylsiloxane) microchannel; (ii) a second set of parallel microchannels
      was then used to immobilize multiple His-tagged proteins onto this pattern at
      discrete locations. SPR imaging measurements were employed to characterize the
      immobilization and specificity of His-tagged fusion proteins to the NTA surface.
      SPR imaging measurements were also used with the His-tagged fusion protein arrays
      to study multiple antibody-antigen binding interactions and to monitor the
      sequence-specific interaction of double-stranded DNA with TATA box-binding
      protein. In addition, His-tagged fusion protein arrays created on gold surfaces
      were also used to monitor antibody binding with fluorescence microscopy in a
      sandwich assay format.

PMID- 14674450
TI  - Faceted design of channels for low-dispersion electrokinetic flows in
      microfluidic systems.
AB  - A novel methodology for designing microfluidic channels for low-dispersion,
      electrokinetic flows is presented. The technique relies on trigonometric
      relations that apply for ideal electrokinetic flows, allowing faceted channels to
      be designed using common drafting software and a hand calculator. Flows are
      rotated and stretched along the abrupt interface between adjacent regions having
      differing specific permeability--a quantity with dimensions of length that we
      introduce to derive the governing equations. Two-interface systems are used to
      eliminate hydrodynamic rotation of bands injected into channels. Regions bounded
      by interfaces form faceted flow "prisms" with uniform velocity fields that can be
      combined with other prisms to obtain a wide range of turning angles and expansion
      ratios. Lengths of faceted prisms can be varied arbitrarily, simplifying chip
      layout and allowing the ability to reduce unwanted effects such as transverse
      diffusion and Joule heating for a given faceted prism. Designs are demonstrated
      using two-dimensional numerical solutions of the Laplace equation.

PMID- 14674451
TI  - Multimode detection of hydrogen gas using palladium-covered silicon micro
      channels.
AB  - Palladium was electrodeposited onto lithographically patterned Si(100) "micro
      channels" with dimensions of 2 microm (width) x 100 microm (length). The
      properties of these Pd-covered Si micro-channels for detecting dihydrogen gas
      were then evaluated. Pd electrodeposition was carried out under conditions
      favoring an instantaneous nucleation and growth mechanism. This strategy produced
      size-similar Pd particles at a coverage of (4-6) x 10(9) cm(-2) within the
      confines of the Si micro-channel. When the mean particle radius, ro, was smaller
      than a critical value (ro < rc = 70-85 nm), each Pd particle was well separated
      on the surface from adjacent particles, on average, and no response to H2 gas
      attributable to the micro-channel was observed. As Pd particles were grown
      larger, to a mean radius of ro approximately equal to rc, adjacent particles on
      the surface touched and the electrical resistance of the micro-channel dropped by
      several orders of magnitude. These "type 2" H2 sensors exhibited a rapid (< 1 s),
      reversible decrease in their resistance in response to exposure to H2 above 0.5%,
      but a minimum resistance was observed at 1-2%, and a resistance increase was seen
      at higher H2 concentration. This complex behavior resulted from the existence of
      three mechanisms for charge transport across the micro-channel. If still larger
      quantities of Pd were deposited, the Pd particle ensemble coalesced into an
      electrically continuous film. These "type 3" sensors became more resistive in the
      presence of H2, not more conductive as seen for sensors of types 1 and 2, but the
      amplitude of this response was smaller than seen for type 2 sensors.

PMID- 14674452
TI  - Room-temperature single-nucleotide polymorphism and multiallele DNA detection
      using fluorescent nanocrystals and microarrays.
AB  - We report two cDNA microarray-based applications of DNA-nanocrystal conjugates,
      single-nucleotide polymorphism (SNP) and multiallele detections, using a
      commercial scanner and two sets of nanocrystals with orthogonal emissions. We
      focus on SNP mutation detection in the human p53 tumor suppressor gene, which has
      been found to be mutated in more than 50% of the known human cancers. DNA
      nanocrystal conjugates are able to detect both SNP and single-base deletion at
      room temperature within minutes, with true-to-false signal ratios above 10. We
      also demonstrate microarray-based multiallele detection, using hybridization of
      multicolor nanocrystals conjugated to two sequences specific for the hepatitis B
      and hepatitis C virus, two common viral pathogens that inflict more than 10% of
      the population in the developing countries worldwide. The simultaneous detection
      of multiple genetic markers with microarrays and DNA-nanocrystal conjugates has
      no precedent and suggests the possibility of detecting an even greater number of
      bacterial or viral pathogens simultaneously.

PMID- 14674453
TI  - Detection of CrO4(2-) using a hydrogel swelling microcantilever sensor.
AB  - Hydrogels containing various mounts of tetraalkylammonium salts were used to
      modify microcantilevers for measurements of the concentration of CrO4(2-) in
      aqueous solutions. These microcantilevers undergo bending deflection upon
      exposure to solutions containing various CrO4(2-) concentrations as a result of
      swelling or shrinking of the hydrogels. The microcantilever deflection as a
      function of the concentration of CrO4(2-) ions is nearly linear in most
      concentration ranges. It was found that a concentration of 10(-11) M CrO4(2-) can
      be detected using this technology in a fluid cell. Other ions, such as Br-,
      HPO4(2-), and NO3-, have minimal effect on the deflection of this cantilever. The
      anions SO4(2-) and CO3(2-) could interfere with the CrO4(2-) detection, but only
      at high concentrations (> 10(-5) M). Such hydrogel-coated microcantilevers could
      potentially be used to prepare microcantilever-based chemical and biological
      sensors when molecular recognition agents are immobilized in the hydrogel.

PMID- 14674454
TI  - Direct determination of carbohydrates, amino acids, and antibiotics by microchip
      electrophoresis with pulsed amperometric detection.
AB  - The separation and detection of underivatized carbohydrates, amino acids, and
      sulfur-containing antibiotics in an electrophoretic microchip with pulsed
      amperometric detection (PAD) is described. This report also describes the
      development of a new chip configuration for microchip electrophoresis with PAD.
      The configuration consists of a layer of poly(dimethylsiloxane) that contains the
      microfluidic channels, reservoirs, and a gold microwire, sealed to a second layer
      of poly(dimethylsiloxane). Example separations of carbohydrates, amino acids, and
      sulfur-containing antibiotics are shown. The effect of the separation and
      injection potentials, buffer pH and composition, injection time, and PAD
      parameters were studied in an effort to optimize separations and detection.
      Detection limits ranging from 6 fmol (5 microM) for penicillin and ampicillin to
      455 fmol (350 microM) for histidine were obtained.

PMID- 14674455
TI  - Screening of biomarkers in rat urine using LC/electrospray ionization-MS and two
      way data analysis.
AB  - Biofluids, like urine, form very complex matrixes containing a large number of
      potential biomarkers, that is, changes of endogenous metabolites in response to
      xenobiotic exposure. This paper describes a fast and sensitive method of
      screening biomarkers in rat urine. Biomarkers for phospholipidosis, induced by an
      antidepressant drug, were studied. Urine samples from rats exposed to citalopram
      were analyzed using solid-phase extraction (SPE) and liquid chromatography mass
      spectrometry (LC/MS) analysis detecting negative ions. A fast iterative method,
      called Gentle, was used for the automatic curve resolution, and metabolic
      fingerprints were obtained. After peak alignment principal component analysis
      (PCA) was performed for pattern recognition, PCA loadings were studied as a means
      of discovering potential biomarkers. In this study a number of potential
      biomarkers of phospholipidosis in rats are discussed. They are reported by their
      retention time and base peak, as their identification is not within the scope of
      the study. In addition to the fact that it was possible to differentiate control
      samples from dosed samples, the data were very easy to interpret, and signals
      from xenobiotic-related substances were easily removed without affecting the
      endogenous compounds. The proposed method is a complement or an alternative to
      NMR for metabolomic applications.

PMID- 14674456
TI  - Determination of binding constants on microarrays with confocal fluorescence
      detection.
AB  - Confocal laser scanning microscopy was employed for the determination of binding
      constants of receptor-ligand interactions in a microarray format. Protocols for a
      localized immobilization of amine containing substances on glass via GOPTS (3
      glycidyloxypropyl)trimethoxysilane) were optimized with respect to the detection
      of ligand binding by fluorescence. Compatibility with miniaturization by
      nanopipetting devices was ensured during all steps. The interaction of the
      tripeptide L-Lys-D-Ala-D-Ala with vancomycin immobilized on glass served as a
      model. To minimize consumption of ligand, binding constants were determined by
      stepwise titration of binding sites. The binding constant of the unlabeled ligand
      was determined by competitive titration with a fluorescently labeled analogue.
      The determined binding constants agreed well with those determined by other
      techniques, previously. Labeled ligand bound stronger than the unlabeled one.
      This difference was dye-dependent. Still, binding was specific for the tripeptide
      moiety confirming that ligand and fluorescent analogue competed for the same
      binding sites these results validate the determination of binding constants by
      competitive titration. The protocols established for confocal fluorescence
      detection are applicable to axially resolved detection modalities and screening
      for unlabeled ligands by competitive titration in general.

PMID- 14674457
TI  - Total protein determinations by particle beam/hollow cathode optical emission
      spectroscopy.
AB  - A novel method for quantitative total protein determinations is presented. Total
      protein content is determined by particle beam/hollow cathode optical emission
      spectroscopy (PB/HC-OES) through monitoring of carbon atomic emission. The PB/HC
      OES offers such advantages as ease of operation, exclusion of labor-intensive
      sample pretreatment processes, rapid analysis, high sensitivity, and low
      detection limit. The method could also be adapted to be integrated to current
      microfluidics devices. Parametric optimization for sample introduction,
      nebulization, desolvation, and hollow cathode source conditions is performed for
      the analysis of aqueous bovine serum albumin solutions. Response curves of C (I)
      193.0-nm emission were obtained under the optimized conditions with both 10% HCl
      and 100 micromL KCl added to the sample matrix as potential carriers. The
      detection limit for triplicate injections of bovine serum albumin standards was
      found to be on the single-nanogram level with 200-microL injections. The addition
      of KCl significantly improved the sensitivity, supporting the proposed "carrier
      effect" of chloride salts in the particle transport process. Results obtained
      here suggest a range of applications for the use of the PB/HC-OES source for
      total protein determinations; emphasis here is future use in assessing protein
      quantification in microfluidic systems.

PMID- 14674458
TI  - Analysis of octyl- and nonylphenol and their ethoxylates in water and sediments
      by liquid chromatography/tandem mass spectrometry.
AB  - The ubiquitous presence of alkylphenol ethoxylates in the environment as well as
      concern for endocrine disruption effects in biota caused by their degradation
      products (such as octyl- and nonylphenol) has raised interest in the
      environmental fate of these compounds. As part of an effort to model their
      behavior in a subestuary of the Chesapeake Bay, a quantitative method for the
      analysis of octyl- and nonylphenol, and their ethoxylates (1-5) in water and
      sediment was developed. Extraction procedures are based on solid-phase extraction
      techniques. Identification and quantitation of the analytes is done by liquid
      chromatography coupled to tandem mass spectrometry. Instrument detection limits
      for the compounds ranged from 0.1 to 9 pg injected on column, which allowed
      method detection limits of 0.04-3 ng/L in water and 0.2-13 ng/g of dry weight in
      sediment. The method was used to analyze water and sediment from the Back River,
      MD, where concentrations for the individual compounds ranged from <8 to 200 ng/L
      in water and <9 to 6700 ng/g of dry weight in sediment. Additionally, structural
      information obtained in the mass spectrometer is presented that supports previous
      observations that nonylphenol and its ethoxylates are composed mainly of isomers
      with a tertiary alpha-carbon.

PMID- 14674459
TI  - Quantification of proteins and metabolites by mass spectrometry without isotopic
      labeling or spiked standards.
AB  - A new method is presented for quantifying proteomic and metabolomic profile data
      by liquid chromatography-mass spectrometry (LC-MS) with electrospray ionization.
      This biotechnology provides differential expression measurements and enables the
      discovery of biological markers (biomarkers). Work presented here uses human
      serum but is applicable to any fluid or tissue. The approach relies on linearity
      of signal versus molecular concentration and reproducibility of sample
      processing. There is no use of isotopic labeling or chemically similar standard
      materials. Linear standard curves are reported for a variety of compounds
      introduced into human serum. As a measure of analytical reproducibility for
      proteome and metabolome sampling, median coefficients of variation of 25.7 and
      23.8%, respectively, were determined for approximately 3400 molecular ions (not
      counting their numerous isotopes) from 25 independently processed human serum
      samples, corresponding to a total of 85000 individual molecular ion measurements.

PMID- 14674460
TI  - Simultaneous determination of five tobacco-specific nitrosamines in mainstream
      cigarette smoke by isotope dilution liquid chromatography/electrospray ionization
      tandem mass spectrometry.
AB  - Tobacco-specific nitrosamines (TSNAs) have been previously implicated as a source
      of carcinogenicity in tobacco and cigarette smoke. Accurate quantification of
      these chemicals is needed to help assess public health risk. We have developed
      and validated a specific and sensitive method to simultaneously measure five
      TSNAs in the particulate phase of mainstream tobacco smoke. Cigarette smoke
      particulate, produced using standardized machine smoking protocols, was collected
      on a Cambridge filter pad. The particulate matter was extracted using methylene
      chloride, back extracted into aqueous solution, further purified by solid-phase
      extraction, and analyzed by liquid chromatography/electrospray ionization tandem
      mass spectrometry using isotopically labeled analogues as internal standards.
      Limits of detection for this method ranged from 0.05 to 1.23 ng/mL using an
      injection volume of 20 microL. A linear calibration range spanning 2.5-2500 ng/mL
      was adequate to measure TSNA levels in cigarette smoke. The method achieved
      excellent reproducibility and accuracy. The identity of each TSNA was established
      by chromatographic retention time, analyte-specific fragmentation patterns, and
      relative peak area ratios of two product/precursor ion pairs. This new method
      provides higher sensitivity, specificity, and throughput than earlier methods for
      TSNA determination.

PMID- 14674461
TI  - Analysis of phenothiazine and its derivatives using LC/electrochemistry/MS and
      LC/electrochemistry/fluorescence.
AB  - The on-line electrochemical conversion of phenothiazine and its derivatives after
      liquid chromatographic separation has been studied by mass spectrometry and
      fluorescence spectroscopy. In an electrochemical cell consisting of porous glassy
      carbon, the phenothiazines are readily converted to oxidized products, which can
      be detected by on-line fluorescence spectroscopy and mass spectrometry. The
      method allows rapid investigations on the electrochemical oxidation pathways, as
      demonstrated for phenothiazine itself. The phenothiazine derivatives are
      transferred into their strongly fluorescent sulfoxides. Based on this reaction,
      an LC/electrochemistry/fluorescence method was developed that allows for limits
      of detection between 5 x 10(-9) and 4 x 10(-8) mol/L and limits of quantification
      between 2 x 10(-8) and 1 x 10(-7) mol/L for the individual phenothiazines. The
      linear ranges comprised three decades starting at the limit of quantification.

PMID- 14674462
TI  - Direct electron transfer of heme- and molybdopterin cofactor-containing chicken
      liver sulfite oxidase on alkanethiol-modified gold electrodes.
AB  - Direct heterogeneous electron transfer (ET) of sulfite oxidase (SOx), a heme- and
      molybdopterin cofactor-containing intermembrane enzyme, was studied on
      alkanethiol-modified Au electrodes both with SOx entrapped between the modified
      Au electrode and a permselective membrane and with SOx adsorbed at the electrode
      surface, in the absence of any membrane. SOx in direct electronic communication
      with the electrode surface gave a quasi-reversible electrochemical signal with a
      midpoint potential of--120 mV vs Ag/AgCl corresponding to the redox
      transformations of the heme domain of SOx and with a heterogeneous ET constant in
      the order of 15 s(-1). The efficiency of the bioelectrocatalytic 2e- oxidation of
      sulfite catalyzed by SOx in direct ET exchange with the electrode was shown to
      depend essentially on the nature of the alkanethiol layer. Adsorption and
      orientation of SOx on an 11-mercapto-1-undecanol (MuD-OH) self-assembled
      monolayer, i.e., terminally functionalized with OH groups, provided efficient
      catalytic oxidation of sulfite, contrary to nonfunctionalized alkanethiols, e.g.,
      1-decanethiol, or alkanethiol layers terminally functionalized with NH2 groups.
      Comparative studies with short-chain alkanethiols, e.g., cysteamine and 2
      mercaptoethanol, revealed an evidently different mode of adsorption of SOx on
      these layers, onto which SOx was not catalytically active. Coadsorption of MuD-OH
      and 11-mercapto-1-undecanamine improved the surface properties of the SAM,
      resulting in a higher surface coverage with bioelectrocatalytically active SOx
      but not in an increased apparent catalytic rate constant, kcat, ranging in the
      order of 18-24 s(-1) at pH 7.4. The achieved efficiency of SOx
      bioelectrocatalysis in direct ET reaction between the modified electrode and the
      enzyme approached the rates characteristic for the catalysis mediated by
      cytochrome c, the natural redox partner of SOx, thus implying the retention of
      the biological function of SOx under the heterogeneous electrode reaction
      conditions. Results obtained enable the development of a third-generation
      biosensor for sulfite monitoring.

PMID- 14674463
TI  - High-stability ionic liquids. A new class of stationary phases for gas
      chromatography.
AB  - Room-temperature ionic liquids are a class of non-molecular ionic solvents with
      low melting points. Their properties have the potential to be especially useful
      as stationary phases in gas-liquid chromatography (GLC). A series of common ionic
      liquids were evaluated as GLC stationary phases. It was found that many of these
      ionic liquids suffer from low thermal stability and possess unfavorable retention
      behavior for some classes of molecules. Two new ionic liquids were engineered and
      synthesized to overcome these drawbacks. The two new ionic liquids (1-benzyl-3
      methylimidazolium trifluoromethanesulfonate and 1-(4-methoxyphenyl)-3
      methylimidazolium trifluoromethanesulfonate) are based on "bulky" imidazolium
      cations with trifluoromethanesulfonate anions. Their solvation characteristics
      were evaluated using the Abraham solvation parameter model and correlations made
      between the structure of the cation and the degree to which the ionic liquids
      retain certain analytes. The new ionic liquids have good thermal stability up to
      260 degrees C, provide symmetrical peak shapes, and because of their broad range
      of solvation-type interactions, exhibit dual-nature selectivity behavior. In
      addition, the ionic liquid stationary phases provided different retention
      behavior for many analytes compared to a commercial methylphenyl polysiloxane GLC
      stationary phase. This difference in selectivity is due to the unique solvation
      characteristics of the ionic liquids and makes them very useful as dualnature GLC
      stationary phases.

PMID- 14674464
TI  - A tool for studying contact electrification in systems comprising metals and
      insulating polymers.
AB  - We describe an analytical system for in situ measurement of the charge that
      develops by contact electrification when a ferromagnetic sphere rolls on the
      surface of a polymer. This system makes it possible to survey the ability of
      polymeric surfaces to charge by contact electrification. Because the measurement
      of charge using this tool does not require physical contact of the charged sphere
      with the measuring electrode, it also enables the kinetics of charging to be
      examined. The research has focused on the contact charging of spheres having a
      core-and-shell geometry (a common core of ferromagnetic steel, and a variable
      shell of thin films of metals, or metals with surface oxides) rolling on the
      surface of polymeric slabs; it has generated an internally consistent set of data
      that include the polarity and magnitude of charging for a homologous series of
      polymers that differ chemically in the pendant group on a polyethylene backbone.

PMID- 14674465
TI  - Development of an internal monostandard instrumental neutron activation analysis
      method based on in situ detection efficiency for analysis of large and
      nonstandard geometry samples.
AB  - A k0-based internal monostandard instrumental neutron activation analysis method
      for determination of relative elemental concentration in samples of large size
      and irregular geometry has been developed. In this method, one of the elements
      present in the sample is used as comparator. A priori knowledge of the
      concentration of one of the constituents is required to convert the relative
      concentration into absolute values. The problems of gamma-ray self-attenuation
      and geometrical effects that arise in the assay of large and nonstandard geometry
      samples were overcome by an in situ relative detection efficiency calibration
      procedure, which requires one or more activation products emitting gamma-rays
      over a wide range of the spectrum. To minimize the problem of neutron flux
      perturbations that may arise in large samples, irradiations were carried out
      using a thermal column with thermal neutron component of more than 99.9%. The
      method has been standardized with samples of silica (approximately 0.5 kg) and
      water (0.5 L) spiked with known amounts of different elements and has been
      advantageously applied to some alloy and metal samples of irregular geometry,
      where complete compositional characterization was carried out using mass balance.
      This approach is highly valuable for analysis of large, irregularly shaped
      samples if not too high demands are set to the degree of accuracy.

PMID- 14674466
TI  - Monitoring hydrogen peroxide in the extracellular space of the brain with
      amperometric microsensors.
AB  - Interest in the detection of hydrogen peroxide in living brain tissue is growing
      for several reasons. Peroxide and other reactive oxygen species are implicated in
      neurodegenerative disorders and appear to have neuromodulatory functions in the
      brain. Also, there is a need to measure peroxide levels as a companion to
      measurements with amperometric sensors that rely on enzymes to generate peroxide
      for the detection of glutamate, choline, and glucose. Herein, we report on
      measurements performed in the brain of anesthetized rats with carbon fiber
      amperometric sensors coated with a cross-linked redox polymer film that contains
      horseradish peroxidase. Prior work with these sensors has established that they
      are both sensitive and selective toward hydrogen peroxide. When implanted in the
      striatal region of the rat brain, a biphasic response is observed upon electrical
      stimulation of the dopaminergic pathway that innervates the striatal tissue. No
      response is observed at sensors lacking HRP, which are not sensitive to peroxide,
      suggesting that the biphasic response is due to the production of hydrogen
      peroxide by two separate mechanisms. Additional measurements of dopamine and
      oxygen, and the administration of two drugs with well-known effects on the
      biochemical kinetics of the dopamine neurons, are used to identify those
      mechanisms. One appears to be the production of peroxide upon the oxidation of
      dopamine by molecular oxygen. This occurs during the electrical stimulation
      itself, which elevates both dopamine and oxygen levels in the extracellular
      space. The other appears to be the production of peroxide as a byproduct in the
      oxidative metabolic conversion of dopamine to DOPAC by the mitochondrial enzyme,
      monoamine oxidase. The production of peroxide due to dopamine metabolism is also
      observed after rats receive a dose of L-DOPA, a drug used in the treatment of
      Parkinson's disease.

PMID- 14674467
TI  - Atrazine sensor based on molecularly imprinted polymer-modified gold electrode.
AB  - Molecularly imprinted polymers (MIP) have been elucidated to work as artificial
      receptors. In our present study, a MIP was applied as a molecular recognition
      element to a chemical sensor. We have constructed an atrazine sensor based on a
      MIP layer selective for atrazine and its electrochemical reduction on gold
      electrode. The atrazine sensor was fabricated by directly polymerizing the
      atrazine-imprinted polymer composed from methacrylic acid and ethylene glycol
      dimethacrylate onto the surface of a gold electrode. By introducing LiCl into the
      MIP, atrazine was reduced below -800 mV vs Ag/AgCl reference electrode, at pH 3.
      The cathodic current of atrazine depended on the concentration of atrazine at the
      range of 1-10 microM. The sensor exhibited a selective response to atrazine. A
      nonimprinted polymer-modified electrode did not show selective response to
      atrazine, thus implying that the imprinted polymer acts as recognition element of
      atrazine sensor.

PMID- 14674468
TI  - Capillary isoelectric focusing of proteins with liquid core waveguide laser
      induced fluorescence whole column imaging detection.
AB  - A capillary isoelectric focusing (CIEF) system with liquid core waveguide (LCW)
      laser-induced fluorescence whole column imaging detection was developed in this
      study. A Teflon AF 2400 capillary was used as both the separation channel and the
      axially illuminated LCW. The excitation light was introduced at one end of the
      capillary, and propagated forward within the capillary. As the Teflon AF 2400
      capillary has a refractive index (n = 1.29-1.31) lower than that of water (n =
      1.33), total internal reflection was very apparent The employment of the Teflon
      AF 2400 capillary avoided the use of high refractive index additives such as
      glycerol, accommodating the system to wider applications. Due to its inert
      chemical properties, the capillary exhibited limited protein adsorption and
      electroosmotic flow; thus, the need for capillary preconditioning with polymeric
      solution and the addition of polymeric additives into the sample mixture can be
      avoided. Three types of proteins, naturally fluorescent proteins, covalently
      labeled proteins, and noncovalently labeled proteins, were examined using this
      method. CIEF under denaturing conditions was also explored, and several
      advantages over the native mode were found. When compared to a commercially
      available instrument with UV detection, the separation efficiency and peak
      capacity were similar while the detection sensitivity was enhanced by 3-5 orders
      of magnitude.

PMID- 14674469
TI  - Structural characterization of oligosaccharides using MALDI-TOF/TOF tandem mass
      spectrometry.
AB  - Extensive cross-ring fragmentation ions, which are very informative of the
      linkages of the monosaccharide residues constituting these molecules, were
      readily observed in the MALDI-TOF/TOF/MS/MS spectra of oligosaccharides. These
      ions, in some cases, were more intense than the commonly observed Y and B ions.
      The A-type ions observed for the simple oligosaccharides allowed the distinction
      between alpha(1-4)- and alpha(1-6)-linked isobaric structures. The distinction
      was based not merely on the differences in the type of ions formed, but also on
      the ion intensities. For example, both alpha(1-4)- and alpha(1-6)-linked isobaric
      structures produce ions resulting from the loss of approximately 120 m/z units,
      but with different intensities, as a result of the fact that they correspond to
      two different ions (i.e., 0,4A- and 2,4A-ions), requiring different energies to
      be formed. Abundant A- and X-type ions were also observed for high-mannose N
      glycans, allowing the determination of linkages. In addition, the high resolution
      furnished by MALDI-TOF/TOF allowed determination of certain ions that were
      commonly overlooked by MALDI-TOF or MALDI-magnetic sector instruments as a result
      of their lower resolution. Moreover, as a result of the fact that MS/MS spectra
      for parent ions and all fragment ions are acquired under the same experimental
      conditions, accurate determination of the molar ratios of isomeric glycans in a
      mixture analyzed simultaneously by MALDI-TOF/TOF tandem MS becomes possible.

PMID- 14674470
TI  - A graphitized-carbon monolithic column.
AB  - The preparation of a novel carbon monolithic column for high performance liquid
      chromatography is described. A phenolic resin rod with embedded 10-microm silica
      beads was prepared by acid-catalyzed polymerization of a resorcinol/iron(III)
      complex and formaldehyde. This rod was carbonized and graphitized under inert
      atmosphere with a programmed temperature cycle from room temperature to 1250
      degrees C. Subsequently, the silica beads along with iron catalysts were removed,
      leaving a porous carbon rod. Imaging of this monolithic rod by scanning and
      transmission electron microscopies revealed a highly interconnected bimodal
      porous structure. The porosity and pore size distribution of the mesopores were
      characterized by N2 absorption/desorption. Graphene sheets were found in the TEM
      images of the carbon rod, and the graphite index was characterized by Raman
      spectrum and X-ray diffraction. A monolithic column prepared with the
      aforementioned carbon rod was evaluated using a mixture of alkylbenzenes. It
      exhibited an excellent separation power and a low hydraulic resistance. The
      bundle-of-capillaries model was used to characterize the hydrodynamics of this
      monolith. Its permeability was found to agree well with the theoretical one.

PMID- 14674471
TI  - Chromatographic separation of nitrogen, argon, and oxygen in dissolved air for
      determination of triple oxygen isotopes by dual-inlet mass spectrometry.
AB  - A chromatographic system was developed to separate oxygen from nitrogen, argon,
      carbon dioxide, and water vapor mixture for the determination of precise isotopic
      ratio measurements of oxygen in dissolved air. This system separates oxygen not
      only quantitatively but also rapidly as well; typical oxygen separation takes
      about 30 min. Fractionation of oxygen between liquid and gas phase was found to
      be similar to that of earlier reports.

PMID- 14674472
TI  - Linking mass spectrometry and slab-polyacrylamide gel electrophoresis by passive
      elution of lipopolysaccharides from reverse-stained gels: analysis of gel
      purified lipopolysaccharides from Haemophilus influenzae strain Rd.
AB  - Haemophilus influenzae is an important cause of human disease, and its
      lipopolysaccharide (LPS) is known to be a major virulence factor. H. influenzae
      produces short-chain LPS of which the heterogeneity is often visualized by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) using silver
      staining for detection. Individual bands have not previously been recovered by
      this method in quantities sufficient for mass spectrometry. In an attempt toward
      the development of sensitive mass spectrometrical strategies to be used in
      structural studies of H. influenzae LPS and LPS from other bacteria, we have
      applied here our previously described slab-PAGE-based micropurification method to
      obtain unmodified LPS fractions of high purity (>95%) from a crude LPS
      preparation of H. influenzae strain Rd. Two LPS-fractions were obtained which,
      after a procedure including mild acid hydrolysis, dephosphorylation, and
      permethylation of the resulting oligosaccharides, were subjected to tandem
      electrospray ionization mass spectrometry (ESI-MS/MS). The quantities of
      micropurified LPS fractions-the recovery of LPS in terms of total mass was 30%
      were found sufficient to allow the characterization of LPS glycoforms. The ESI-MS
      spectra of the individual bands showed reduced heterogeneity. Furthermore, the
      integrity of the micropurified LPS was confirmed. The spectra-displayed molecular
      ions showed improved intensity, increased respective signal-to-noise ratios
      demonstrating the sensitivity of analysis. Consequently, both the direct
      determination of the molecular masses of the gel-separated LPS glycoforms and
      sequence analyses using ESI-MS/MS were possible.

PMID- 14674473
TI  - Identification and characterization of conjugated fatty acid methyl esters of
      mixed double bond geometry by acetonitrile chemical ionization tandem mass
      spectrometry.
AB  - Fatty acids with conjugated double bonds have attracted great interest because of
      their reported potent bioactivities. However, there are currently no rapid
      methods for their structural characterization. We report here a convenient mass
      spectrometry-based strategy to establish double bond geometry by analysis of
      collisional dissociation products of cis/trans and trans/cis conjugated linoleic
      acids (CLAs), as methyl esters, and to distinguish CLAs from homoallylic
      (methylene-interrupted) fatty acids in a single-stage mass spectrum. A series of
      CLA standards with double bond positions 6,8; 7,9; 8,10; 9,11; 10,12; 11,13;
      12,14; and 13,15, with all four possible geometries (cis/trans; trans/cis;
      cis/cis; trans/trans) were analyzed. The m/z 54 (1-methyleneimino)-1-ethenylium
      ion, generated by self-reaction of acetonitrile under chemical ionization
      conditions, reacts with unsaturated fatty acids to yield an [M + 54]+ ion, which
      decomposes in the single-stage mass spectrum by loss of neutral methanol to form
      [M + 54 - 32]+. The ratio of [M + 54]+/[M + 54 - 32]+ in the single-stage mass
      spectra of CLA isomers is 1 order of magnitude less than for homoallylic diene
      FAME. Collisional dissociation of the [M + 54]+ ion yields two diagnostic ions
      that contain the alpha- and omega-carbon atoms and is characteristic of double
      bond position in the analyte. The fragment vinylic to the trans double bond is
      significantly more abundant than that for the cis double bond, revealing double
      bond geometry. The ratio of alpha to we diagnostic ion abundances is >4.8 for
      cis/trans isomers, <0.5 for trans/cis isomers, and 0.7-3.2 for cis/cis and
      trans/trans isomers. This method provides a rapid alternative to conventional
      conjugated fatty acid analysis and, together with complementary elution time
      information provided by gas chromatography, enables rapid, positive
      identification of double bond position and geometry in most CLA FAME.

PMID- 14674474
TI  - A microfluidic device with an integrated waveguide beam splitter for velocity
      measurements of flowing particles by Fourier transformation.
AB  - A microfabricated capillary electrophoresis device for velocity measurements of
      flowing particles is presented. It consists of a 1 x 128 planar waveguide beam
      splitter monolithically integrated with an electrically insulated fluidic channel
      network for fluorescence excitation at multiple points. Stray light rejection
      structures are included in order to suppress unwanted light between the detection
      regions. The emission pattern of particles passing the detection region was
      collected by a photomultiplier tube that was placed in close proximity to the
      channel, thereby avoiding the use of transfer optics. The integrated planar
      waveguide beam splitter was, furthermore, permanently connected to the light
      source by a glued-on optical fiber, to achieve a robust and alignment-free
      operation of the system. The velocity was measured using a Fourier transformation
      with a Shah function, since the response of the light array was designed to
      approximate a square profile. Deviations from this response were observed as a
      result of the multimode nature of the integrated waveguides.

PMID- 14674475
TI  - Use of a microchip device coupled with mass spectrometry for ligand screening of
      a multi-protein target.
AB  - Nanoflow electrospray mass spectrometry has been applied previously to
      investigate noncovalent protein-protein and protein-ligand interactions. Here we
      evaluate a commercial microchip device for this application. We show that the
      microchip can be used to obtain mass spectra of the noncovalent tetramer
      transthyretin. The device showed a 10-fold increase in signal stability compared
      with a nanoflow capillary and a high level of nozzle-to-nozzle reproducibility.
      Binding of the natural ligand thyroxine was clearly observed, and a range of
      small molecules proposed as inhibitors of transthyretin amyloidosis were shown to
      be effective in stabilizing the tetramer. We propose that measuring the ability
      of small molecules to stabilize protein complexes using this automated microchip
      technology will enable high-throughput screening of multi-protein complexes by
      mass spectrometry.

PMID- 14674477
TI  - Use of mouse genetics for studying inner ear development.

PMID- 14674478
TI  - Formation of the outer and middle ear, molecular mechanisms.

PMID- 14674479
TI  - Molecular basis of inner ear induction.

PMID- 14674481
TI  - Growth factors and early development of otic neurons: interactions between
      intrinsic and extrinsic signals.

PMID- 14674476
TI  - Molecular conservation and novelties in vertebrate ear development.

PMID- 14674480
TI  - Molecular basis of otic commitment and morphogenesis: a role for homeodomain
      containing transcription factors and signaling molecules.

PMID- 14674482
TI  - Neurotrophic factors during inner ear development.

PMID- 14674483
TI  - FGF signaling in ear development and innervation.

PMID- 14674484
TI  - The roles of retinoic acid during inner ear development.

PMID- 14674485
TI  - Hair cell development in higher vertebrates.

PMID- 14674486
TI  - Cell adhesion molecules during inner ear and hair cell development, including
      notch and its ligands.
AB  - Cellular adhesion plays a key role in a number of unique developmental events,
      including proliferation, cell fate, morphogenesis, neurite outgrowth,
      fasciculation, and synaptogensis. The number of families of molecules that can
      mediate cell adhesion and the number of members of each of those families has
      continued to increase over time. Moreover, the potential for the formation of
      different pairs of heterodimers with different binding specificities, and for
      both homo- and hetero-dimeric interactions suggest that a vast number of specific
      signaling events can be mediated through the expression of different combinations
      of adhesion factors at different developmental time points. By comparison with
      the number of known adhesion molecules and their potential effects, our
      understanding of the role of adhesion in ear development is extremely limited.
      The patterns of expression for some adhesion molecules have been determined for
      some aspects of inner ear development. Similarly, with a few exceptions,
      functional data to indicate the roles of these adhesion molecules are also
      lacking. However, a consideration of even the limited existing data must lead to
      the conclusion that adhesion molecules play key roles in all aspects of the
      development of the auditory system. Unique expression domains for different
      groups of adhesion molecules within the developing otocyst and ear strongly
      suggest a role in the determination of different cellular domains. Similarly, the
      specific expression of adhesion molecules on developing neurites and their target
      hair cells, suggests a key role for adhesion in the establishment of neuronal
      connections and possible the development of tonotopy. Finally, the recent
      demonstration that Cdh23 and Pcdh15 play specific roles in the formation of the
      hair cell stereociliary bundle provides compelling evidence for the importance of
      adhesion molecules in the development of stereocilia. With the imminent
      completion of the mouse genome, it seems likely that the number of adhesion
      molecules can soon be fixed and that it will then be possible to generate a more
      comprehensive map of expression of these molecules within the developing inner
      ear. At the same time, the generation of new transgenic and molecular
      technologies promises to provide researchers with new tools to examine the
      specific effects of different adhesion molecules during inner ear development.

PMID- 14674487
TI  - Genes controlling the development of the zebrafish inner ear and hair cells.

PMID- 14674488
TI  - Functional development of hair cells.

PMID- 14674489
TI  - The cell cycle and the development and regeneration of hair cells.

PMID- 14674490
TI  - Histological, morphological, profilometric and optical changes of human tooth
      enamel after microabrasion.
AB  - PURPOSE: To determine the loss of enamel after a single 20-secondsapplication of
      a microabrasion slurry and to evaluate structural changes by means of laser
      fluorescence, and microscopic and optical measurements. METHODS: Defined buccal
      areas with a diameter of 2 mm from 16 extracted human molars were demineralized
      for 12 weeks using a demineralization gel (pH 4.8). The created artificial white
      spot lesions were divided corono-apically in control and test sites, using a
      rubber cement that prospectively covered the untreated control site. Teeth were
      divided into two groups of eight teeth each. One group was treated with an
      abrasive cleaning paste (Pell-ex) and the other group with a commercially
      available microabrasion slurry (Opalustre) for 20 seconds, applying a load of 200
      g. Before and after treatment, standardized photographs were taken for the
      determination of luminescence and profilometric tracings of the surface, and
      these were recorded for the determination of enamel loss. The grade of
      demineralization was quantified using a laser fluorescence method (Diagnodent).
      Statistical differences were checked using a Mann Whitney and student t-test.
      Replicas of the treated areas were made for scanning electron microscopy (SEM)
      analysis, and teeth were histologically investigated by polarized light
      microscopy. RESULTS: Loss of tooth substance was significantly higher (P < or =
      0.001) for the microabrasion group (134.8 +/- 35.5 microm) compared with the
      abrasive cleaning paste group (4.5 +/- 1.2 microm). After treatment,
      statistically significant differences in fluorescence and luminescence
      measurements could only be detected for microabraded teeth. No significant
      changes were noted for teeth treated with an abrasive cleaning paste.
      Histological findings confirmed removal of the demineralized surface zone when
      microabrading the enamel, whereas no changes were observed in the test group
      treated with an abrasive cleaning paste. Polarized light microscopy did not
      indicate any changes in the mineralization pattern, for example compaction, in
      the treated subsurface zone.

PMID- 14674491
TI  - Relationship between feeding habits and mutans streptococci colonization in a
      group of Spanish children aged 15-20 months.
AB  - PURPOSES: (1) To determine the prevalence of mutans streptococci (MS) in a group
      of Spanish children aged 15-20 months, and (2) to analyze the relationship
      between early colonization and feeding habits. METHODS: In a group of 56
      children, various feeding habits with a possible influence on early MS
      colonization were registered using a questionnaire; saliva samples were taken
      with a tongue blade in order to detect MS presence. RESULTS: As many as 73% of
      the children used a nursing bottle at this age, often with sugar content (cereal
      was added in 83% of children, who were still bottle-fed). The percentage of MS
      colonization was relatively high (46%), although no child presented caries at the
      time. A statistically significant relationship (P < 0.05) was found between MS
      colonization and sweetening of the bottle contents. A relation was also found,
      though not significant, between MS colonization and the absence of breastfeeding
      or, on the other hand, the excessive prolongation of natural or artificial
      feeding.

PMID- 14674492
TI  - Clinical and radiographic evaluation of guided tissue regeneration in the
      treatment of class II furcation defects. A randomized clinical trial.
AB  - PURPOSE: To evaluate the treatment outcomes after guided tissue regeneration
      (GTR) with a bioabsorbable membrane in Class II furcation defects in mandibular
      molars. The open flap debridement (OFD) was used as the control. METHODS: Nine
      patients, with two comparable Class II furcation defects were included in the
      study. After initial preparation, the defects were randomly assigned in each
      patient to either GTR-group or OFD-group. Clinical parameters and standardized
      radiographs were obtained at baseline and 6 months after the surgeries. The
      radiographs were analyzed by subtraction radiography. RESULTS: Comparing baseline
      to 6-month results, both groups showed statistically significant probing depth
      reduction (PD), horizontal clinical attachment level (CAL-h) gain, and increase
      in gingival recession (GR). The vertical clinical attachment level (CAL-v) gain
      was statistically significant only for the OFD-group. Comparing the two
      treatments, no statistically significant differences were found in PD reduction
      (GTR: 1.67 mm; OFD: 2.51 mm, P = 0.26), CAL-v gain (GTR: 0.62 mm; OFD: 1.16 mm,
      P= 0.37), and GR increase (GTR: 1.04 mm; OFD: 1.24 mm, P = 0.31). GTR provided
      complete closure of the furcation defect in two sites and superior horizontal
      clinical attachment level gain (GTR: 2.27 mm; OFD: 1.01 mm, P = 0.05).
      Subtraction radiography showed significant difference in bone height change
      between GTR-group and OFD-group (-0.14 mm and 0.86 mm, respectively; P = 0.028)
      at 6 months.

PMID- 14674493
TI  - Preference and compliance of waterless hand-hygiene products versus soap and
      water.
AB  - PURPOSE: To compare handwashing using traditional antimicrobial soap and water
      with two antimicrobial waterless hand-hygiene products for personal preference
      and compliance. METHODS: Fifty dental and dental hygiene students were randomly
      chosen to participate in the study. All subjects were anonymously observed prior
      to the introduction of the waterless products for handwashing compliance using
      soap and water for 1 week. All subjects were then instructed on the use of a
      waterless gel and foam for handwashing. Both waterless products were used for a
      period of 1 week and students again were anonymously observed. A questionnaire
      was distributed at the conclusion of the study to determine product preference.
      RESULTS: During handwashing with soap and water, the average time the soap was in
      contact with the hands was 7.0 seconds. The average contact time with the gel and
      foam was 15.3 seconds and 20.0 seconds, respectfully. Questionnaire results
      indicated that the foam was significantly preferred over the gel and soap and
      water (54%, 28% and 16%, respectively). The foam was also significantly preferred
      when evaluating fragrance (52%), kindness to the skin (66%), convenience (64%)
      and fastest drying time (54%). Results from this study indicate that the
      waterless foam product was significantly preferred over the waterless gel and
      traditional soap and water for handwashing procedures. Since handwashing
      guidelines, regardless of which product used, recommend a minimum of 15 seconds
      to minimize the number of transient microorganisms on the hands, compliance was
      found only with the foam and the gel.

PMID- 14674494
TI  - Change over time in intra-arch contact point tightness.
AB  - PURPOSE: To examine contact point (CP) tightness of the mandibular dental arch in
      cases with a unilateral first molar (M1) missing, and also investigate the
      influence of time since extraction on CPs tightness. METHODS: CPs tightness was
      measured with a tightness of dental contact point device in 29 patients (9 men,
      20 women), mean age 32.6 +/- 6.5 years, with a unilateral missing M1 and no
      periodontal disease. ANOVA with repeated measures test was used to statistically
      compare CP tightness between extraction (E) and non-extraction (NE) sides, at
      significant level of P < or = 0.05, with CPNE serving as internal control.
      RESULTS: The first CP adjacent to the extraction site between the first and
      second premolar (CP4-5,E) was significantly (P < or = 0.001) lower (29%) than CP4
      5,NE. The difference (NE-E) was reduced to 20% at the more anterior CP (CP3-4,E)
      which was close to but non-significant (P < or = 0.09). Further anterior CPs (CP2
      3, CP1-2) showed a non-significant difference between homologous CPs. Thus,
      reduction in CP tightness was confined to two adjacent teeth anterior to the
      extraction site. The tightness reduction of the posterior dentition (CP4-5 + CP3
      4) was obtained 3 years post-extraction and subsequently maintained a constant
      asymmetry ratio (E/NE = 0.68-0.80) up to 14 years post-extraction.

PMID- 14674495
TI  - Treatment of root caries lesions with chlorhexidine-containing varnishes and
      dentin sealants.
AB  - PURPOSE: To evaluate the effects of chlorhexidine-containing varnishes and dentin
      sealants on the progress of demineralization, cariogenic bacteria and clinical
      appearance of root caries lesions. METHODS: 68 lesions in 22 adult patients, with
      a mean age of 51.3 +/- 13.8 years were enrolled in this study. After the removal
      of soft, infected dentin, all lesions were randomly sealed with (1.) Cervitec,
      used as control (CE), (2.) EC 40 (EC), (3.) Prime and Bond NT (PB) or (4.) Seal &
      Protect (SP). Clinical appearance, laser fluorescence diagnosis (DIAGNOdent) and
      bacteriological status were recorded at intervals of 1 and 3 months. RESULTS:
      Regarding alteration of surface texture and color of the lesions, differences
      between the groups were not detected. Application of EC resulted in suppressed MS
      counts after 3 months (P < 0.05). Initial lower MS counts were observed in the CE
      group (P = 0.053). Laser fluorescence values increased in the chlorhexidine
      groups (CE = 27.9 +/- 17.5, EC = 28.3 +/- 26.0) but remained stable in the
      sealant groups (PB = 15.1 +/- 22.0, SP = 10.2 +/- 7.3), (P < 0.05).

PMID- 14674496
TI  - Bond strengths of tooth-colored posts, effect of sealer, dentin adhesive, and
      root region.
AB  - PURPOSE: To evaluate the effect of sealer, dentin bonding agent, and root region
      on the push-out bond strengths of three tooth colored posts. METHODS: 24
      extracted human single rooted maxillary central incisors and canines were
      endodontically-treated using gutta percha and Roth's 801 or AH26 sealer. Posts
      (Cosmopost, Fibrekor, or Parapost Fiber White) were placed using one of two
      adhesive systems (Parapost Cement Conditioner with Parapost Cement, or One-Step
      with Hi-X Post self-cure resin cement). The push-out test was performed on
      different sections of the root to measure bond strengths. RESULTS: Cosmopost
      showed significantly lower mean bond strengths than either Fibrekor or Parapost.
      Bond strengths of the posts in the crown section were significantly higher than
      those in any of the three root areas measured. Neither the eugenol-containing
      sealer nor the bonding agent type had any effect on bond strength. Post type and
      root region significantly affected bond strength while sealer type or bonding
      agent had no effect on bond strength.

PMID- 14674497
TI  - Influence of enamel surface preparation on composite bond strength.
AB  - PURPOSE: To evaluate the influence of air-particle abrasion and treatments on in
      vitro tensile bond strength of resin composite bonded to human enamel was
      evaluated using a single-bottle adhesive. METHODS: Human teeth were divided into
      12 groups of three treatments (none, 27-microm Al2O3 air-particle abrasion, 50
      microm Al2O3 air-particle abrasion) and four conditioners [none, phosphoric acid
      (PA), NRC (no-rinse conditioner), and PA/NRC]. Bonding agent (Prime & Bond NT)
      and a resin composite (TPH Spectrum) were applied as inverted cones. Specimens
      were stored for 24 hours at 37 degrees C and debonded in tension using a testing
      machine at 0.5 mm/minute. RESULTS: Phosphoric acid treatment used with Prime &
      Bond NT produced the best bond strengths (24 MPa) to enamel for surfaces treated
      with 27-microm air-particle abrasion and for surfaces not treated with air
      particle abrasion (control). With one exception, air-particle abraded surfaces
      resulted in bond strengths between 9 to 16 MPa. NRC with or without the use of
      phosphoric acid in general did not improve tensile bond strength to enamel when
      compared to surfaces not treated with NRC.

PMID- 14674498
TI  - Tensile bond strengths of resin cements to bovine dentin using resin coating.
AB  - PURPOSE: To evaluate the effect of a resin coating technique on dentin tensile
      bond strengths of dual-cured resin cements. METHODS: 10 bovine dentin specimens
      were tested for tensile bond strengths of each of the following four materials:
      Panavia F, Link Max, Bistite II, Rely-X. Bovine dentin ground with 600-grit SiC
      was bonded with a resin cement according to the manufacturers' instructions or
      the resin coating technique, which was used in combination with one coat of a
      dentin adhesive; Clearfil SE Bond, Unifil Bond, One-Up Bond F or Single Bond,
      with one coat of a low viscosity micro-filled resin, Protect Liner-F. Each dentin
      adhesive and the low viscosity micro-filled resin were cured for 10 seconds and
      20 seconds respectively. After 1 day storage in water, the specimens were
      subjected to the tensile bond test at a crosshead speed of 2 mm/minute. The data
      were analyzed by two-way ANOVA and Fisher's PLSD test (P < 0.05). The mode of
      failure after the tensile bond test was classified by visual inspection. The
      resin cement - dentin interfaces were examined by SEM. RESULTS: The tensile bond
      strengths (MPa +/- SD) of four resin cements to dentin with/without resin coating
      were: Panavia F (22.9 +/- 3.1; 10.2 +/- 2.5), Link Max (16.1 +/- 4.4; 9.6 +/-
      3.2), Bistite II (14.8 +/- 3.2; 14.3 +/- 3.9), and Rely-X (15.7 +/- 4.7; 13.5 +/-
      4.5), respectively. The resin coating significantly improved the bond strengths
      of resin cements to dentin in Panavia F and Link Max, while there were no
      significant differences of mean bond strengths between Bistite II or Rely-X with
      and without resin coating (P> 0.05). Regarding the fracture modes, complete and
      partial adhesive failures were observed in the cases without resin coating. For
      the resin coating groups, the fracture modes were much more complicated,
      although, adhesive failures rarely occurred. Hybrid layer formation was observed
      for all materials used.

PMID- 14674499
TI  - Bond strengths of polyacid-modified resin composites and a resin-modified glass
      ionomer cement to primary dentin.
AB  - PURPOSE: To evaluate the bond strengths of three polyacid-modified resin
      composites and one resin-modified glass-ionomer cement to caries-simulated
      primary dentin after 18-months' water immersion. METHODS: Dyract AP, Compoglass
      F, F2000 and Vitremer were used as test materials. Standardized preparations
      cavities with a C-factor of 5 were prepared in primary molars. Half of the
      cavities were stored in a demineralizing media for 7 days to simulate caries
      affected dentin. Thereafter, all preparations were restored with the test
      materials, after which the specimens were stored in water for 18 months, changing
      the water every week. The specimens were subjected to a microtensile test and all
      bond strength data (in MPa) were statistically analyzed using one-way analysis of
      variance (ANOVA) and Tukey HSD tests at P < 0.01. RESULTS: The mean microtensile
      bond strength to normal primary dentin specimens were 11.2 +/- 1.5 (Dyract AP),
      10.6 +/- 2.1 (Compoglass F), 10.8 +/- 1.1 (F2000) and 7.3 +/- 1.6 (Vitremer),
      while those to the caries-simulated dentin were 4.1 +/- 0.7 (Dyract AP), 3.0 +/-
      0.6 (Compoglass F), 2.3 +/- 0.9 (F2000) and 1.9 +/- 0.5 (Vitremer). SEM
      evaluation of the unfractured specimens revealed evidence of gap formation in the
      adhesive interface in all samples.

PMID- 14674500
TI  - Micro-shear bond strengths of adhesive resins to coronal dentin versus the floor
      of the pulp chamber.
AB  - PURPOSE: To evaluate the micro-shear bond strengths to superficial coronal dentin
      and the floor of the pulp chamber using two dentin bonding systems and to compare
      the ultrastructure of the resin-dentin interface of the two regions. METHODS: 30
      non-carious molars were used to obtain 2 mm thick slabs of coronal dentin and
      dentin at the pulp chamber. The specimens in each region were divided into three
      sub-groups to be bonded as follows; Clearfil SE Bond was used according to the
      manufacturer's instructions, Single Bond was applied to either wet dentin (Blot
      dry Group) or air-dried dentin (Dry Group) after phosphoric acid etching. A resin
      composite cylinder 0.5 mm high and 0.75 mm in diameter formed using a vinyl tube
      was bonded to the dentin. Specimens were stored at 37 degrees C for 24 hours in
      water and then stressed in shear at a crosshead speed of 1 mm/minute. The data
      were analyzed with one-way ANOVA and Fisher's PLSD test at the 5% level of
      significance. In addition, the ultrastructure of cross-sectioned dentin surfaces,
      the conditioned dentin surface and the resin dentin interfaces were observed by
      SEM. RESULTS: The bond strengths of Clearfil SE Bond and the Single Bond Blot dry
      group were approximately 40 MPa in coronal dentin and 30 MPa in the dentin at the
      floor of the pulp chamber respectively. However, the bond strengths of Single
      Bond were significantly lower in the Dry condition (MPa) (P < 0.05). SEM
      observations revealed the thickness of the hybrid layer created by Clearfil SE
      Bond in coronal dentin and at the floor of the pulp chamber were less than 1.0
      microm thick. For Single Bond, a 3-4 microm hybrid layer was created in coronal
      dentin, while a thinner hybrid layer was observed in the floor of the pulp
      chamber. Morphological and structural variations in dentin may have influenced
      the bond strengths of the bonding systems to the floor of the pulp chamber.

PMID- 14674501
TI  - Ultra-morphology of self-etching adhesives on ground enamel: a high resolution
      SEM study.
AB  - PURPOSE: To evaluate the effect of different commercial self-etching agents on
      enamel morphology using high-resolution in-lens scanning electron microscopy
      (FEISEM). METHODS: The bonding systems selected for the study were: Prime & Bond
      NT (no-etch technique), Prime & Bond 2.1 (no-etch technique), NRC/Prime and Bond
      NT, Syntac Single Component, Prompt L-Pop, F2000, and Clearfil SE Bond. The
      positive control group was prepared with Single Bond upon etching enamel with the
      proprietary 35% phosphoric acid gel. 24 extracted human molars were equally and
      randomly assigned to the experimental and control groups. All bonding materials
      were applied on enamel following the manufacturers' instructions. A thin layer of
      composite was applied on the polymerized adhesive agent, after which the enamel
      was dissolved to obtain replicas that were observed under a FEISEM. RESULTS:
      Observations revealed different morphological features brought about by the
      adhesive systems. A relationship between the morphological appearance and the pH
      of the adhesive solutions was found. Three different groups of self etching were
      identified: Group 1 showed no or little evidence of modifications on the enamel
      surface (Prime & Bond NT and Prime & Bond 2.1, no-etch technique), Group 2
      revealed major aggressive properties that were able to disclose the prism
      morphology (Syntac Single Component, F2000, Clearfil SE Bond), and Group 3
      (NRC/Prime & Bond NT and Prompt L-Pop) revealed morphological features similar to
      those obtained with Single Bond after etching with phosphoric acid (control
      group).

PMID- 14674502
TI  - Effect of light-curing method and irradiation time on marginal sealing and cavity
      wall adaptation of resin composite restorations.
AB  - PURPOSE: To evaluate the effect of irradiation time on two light-curing methods
      on the marginal sealing and cavity wall adaptation of resin-based composite
      restorations. METHODS: Cylindrical cavities, 1 mm deep and 3 mm in diameter (C
      factor = 2.3) were prepared on flat superficial bovine dentin surfaces. The teeth
      were restored with Clearfil Photo Bond, Clearfil Liner Bond 2 or Super-Bond D
      Liner adhesive systems followed by Photo Clearfil Bright resin-based composite.
      The resins were cured using a conventional method at an output of 600 mW/cm2 for
      60 s, or 600 mW/cm2 for 30 s, or the slow-start curing method at an output of 270
      mW/cm2 for 10 s + 5 s (interval) + 600 mW/cm2 for 50 s or 270 mW/cm2 for 10 s + 5
      s (interval) + 600 mW/cm2 for 20 s. After thermocycling, a dye penetration test
      was carried out. The dye penetration length was calculated as a percentage of the
      total cavity wall length. RESULTS: Slow-start curing method; 270 mW/cm2 10 s + 5
      s (interval) + 600 mW/cm2 for 50 s showed the best marginal sealing and cavity
      wall adaptation. A shorter irradiation time increased cavity wall adaptation when
      the conventional curing method was used. Super-Bond D-Liner showed good marginal
      sealing and resin composite adaptation to the cavity wall regardless of the light
      curing method.

PMID- 14674503
TI  - Sealing properties of a self-etching primer system to normal caries-affected and
      caries-infected dentin.
AB  - PURPOSE: To compare the ability of an experimental antibacterial self-etching
      primer adhesive system to seal exposure sites in normal, caries-affected and
      caries-infected human dentin. METHODS: 30 extracted human third molars were used
      within 1 month of extraction. 10 intact normal teeth comprised the normal group.
      20 teeth with occlusal caries that radiographically extended halfway to the pulp
      were excavated using caries-detector solution (CDS) and a #4 round carbide bur in
      a slowspeed handpiece. Half of those teeth were fully excavated free of CDS
      stained material without exposing the pulp, and were designated as the caries
      affected dentin group. The remaining 10 teeth were excavated as close to the pulp
      as possible without obtaining an exposure, but whose dentin continued to stain
      red with CDS; this group was designated as the caries-infected dentin group. The
      remaining dentin thickness in all of the specimens in the other two groups was
      then reduced to the same extent as the caries-infected group. Direct exposures of
      the pulp chamber were made with a 1/4 round bur in the normal dentin or a 25
      gauge needle in the other two groups. After measuring the fluid flow through the
      exposure, the sites were then sealed with an experimental antibacterial fluoride
      containing self-etching primer adhesive systems (ABF). Fluid conductance was
      remeasured every week for 16 weeks. RESULTS: The fluid conductance through the
      exposure fell 99% in all groups following resin sealing. The seals of normal and
      caries-affected dentin remained relatively stable over the 16 weeks, while the
      seals of caries-infected dentin gradually deteriorated, reaching significance at
      8 weeks. TEM examination revealed very thin (ca. 0.5 mm) hybrid layers in normal
      dentin, 3-4 microm thick hybrid layers in caries-affected dentin and 40 microm
      thick hybrid layers in caries-infected dentin. The tubules of caries-infected
      dentin were enlarged and filled with bacteria. Resin tags passed around these
      bacteria in the top 20-40 microm thereby encapsulating them in resin.

PMID- 14674504
TI  - Effect of different polymerization methods on composite microleakage.
AB  - PURPOSE: To evaluate the microleakage of a condensable resin composite using a
      microhybrid flowable composite as a liner, cured with four different methods of
      polymerization. METHODS: 40 freshly extracted caries-free human premolars and
      molars were used. MO/DO Class II standardized preparations were performed with
      the gingival margin placed 1 mm above the CEJ. Teeth were randomly divided into
      four groups. Group 1 (control group): conventional mode (Elipar Highlight), Group
      2: step mode (Elipar Highlight), Group 3: ramp mode (Elipar Trilight) and Group
      4: pulse mode (VIP). Preparations were etched with 32% phosphoric acid (Uni-Etch)
      and an adhesive system (One-Step) was used according to the manufacturer's
      instructions. Teeth were then restored using a 1 mm layer of flowable composite
      (A2 AEliteflo LV) on the gingival and pulpal floor and condensable composite
      (Pyramid A2 Dentin and A1 Enamel) in 2 mm increments. Teeth were thermocycled
      x500 between 5 degrees C and 55 degrees C with a dwell of 30 seconds and then
      placed in a 0.5% methylene blue dye solution for 24 hours at 37 degrees C.
      Samples were sectioned longitudinally and evaluated for microleakage at the
      gingival margin under a stereomicroscope at x30 magnification. Dye penetration
      was scored using an ordinal scoring system as 0: no penetration; 1: enamel
      penetration; 2: dentin penetration. RESULTS: A Mann-Whitney U Test revealed a
      statistically significant difference between Group 1 with Groups 2, 3 and 4 (P <
      0.001). Group 1 yielded the most microleakage. No statistically significant
      difference was noted between Groups 2, 3 and 4.

PMID- 14674506
TI  - Tensile strength and ultrastructure of a compomer and a composite in aqueous and
      non-aqueous storage media.
AB  - PURPOSE: To compare the ultimate tensile strength (UTS) of a compomer (Dyract AP)
      and a composite (Spectrum TPH) that were stored in an aqueous or a non-aqueous
      medium for up to 180 days. METHODS: 156 hourglass-shaped specimens of each
      material with cylindrical cross-sectional areas along the test regions were
      prepared. For each material, 12 beams were stressed to failure using a
      microtensile testing method to obtain the baseline UTS data. The rest were
      divided into two groups. One group was stored in de-ionized water (W), and the
      other (control) in silicone fluid (O) at 37 degrees C. 12 beams were removed from
      the respective storage medium after 1, 7, 14, 30, 90, 180 days for evaluation of
      the NTS. Materials retrieved from the intact central cylindrical portion of the
      fractured 180-day specimens were prepared for transmission electron microscopy
      (TEM). RESULTS: Baseline UTS for Dyract AP (D) and Spectrum TPH (S) were 76 +/-
      16 MPa and 92 +/- 13 MPa, respectively. One-way ANOVA on ranks and Dunn's
      multiple comparison tests showed that UTS of Groups D-O, S-O and S-W remained
      stable during 180 days and were not significantly different from the baseline
      results. There was a significant drop in UTS in Group D-W after 90 and 180 days
      when compared with the 1-day result (P < 0.05). A highly significant nonlinear
      correlation was also observed in Group D-W between the mean UTS after the first
      day and the storage time (P < 0.01). No difference could be seen between the
      filler-matrix interface in S-O and S-W. A very thin glass-ionomer phase (ca. 200
      nm thick siliceous hydrogel layer) could be observed in D-W, but not in D-O.

PMID- 14674505
TI  - Effects of different acid and sodium hypochlorite treatments on dentin collagen:
      a FEISEM analysis.
AB  - PURPOSE: To evaluate if different acid treatments of dentin surface might remove
      different amount of mineralized dentin, thus exposing and modifying the CF
      network. METHODS: Dentin disks prepared from human third molars with a low-speed
      diamond saw were etched for 15 seconds with the tested acids: citric acid 10%,
      maleic acid 10%, 2.5% oxalic acid, 35% phosphoric acid and 24% EDTA gel.
      Specimens were then submitted to a 5% solution of NaOCl for 2 minutes or 5
      minutes, fixed, and observed utilizing a field emission in lens SEM (FEISEM).
      Control specimens were also prepared by omitting the etching agent and/or the
      NaOCl solution. RESULTS: The different acid treatments created specific dentin
      morphological pattern. CF exposure was in relationship with the acid used. The
      NaOCl solution greatly affects the acid etched dentin by removing the CF,
      nevertheless the effect of NaOCl was greatly influenced by the previous acid
      treatment.

PMID- 14674507
TI  - In vitro fracture resistance of teeth with dentin-bonded ceramic crowns and core
      build-ups.
AB  - PURPOSE: To assess the fracture strength of dentin-bonded crowns placed on cores
      of amalgam, resin composite and viscous glass-ionomer. METHODS: 40 sound
      maxillary premolar teeth were selected. These were mounted in acrylic resin in
      stainless steel molds. The palatal cusp of each tooth was removed in a
      standardized manner to simulate a core build-up preparation. Teeth were randomly
      divided into four groups, and each group was allocated a core material. For Group
      A, the core was pin-retained amalgam, for Group B the core was bonded amalgam,
      for Group C the core material was resin composite and for Group D the core
      material was high-viscosity glass-ionomer material. Cores were then constructed
      to the original tooth dimensions. A standardized crown preparation was made,
      impressions taken and an all-ceramic crown constructed in feldspathic porcelain.
      The crowns were luted in position using a dentin-bonding agent/dual cure resin
      composite cement and the completed specimens subjected to compressive loading in
      a Universal Testing machine at 1 mm/minute. RESULTS: The mean forces to produce
      fracture of the crowns were 1.58 kN (+/- 0.41), 1.35 kN (+/- 0.44), 1.25 kN (+/-
      0.24), and 1.12 kN (+/- 0.25) respectively for groups A, B, C and D. Statistical
      analysis by ANOVA indicated that the pinned amalgam group performed significantly
      better than the glass-ionomer group (P > 0.05).

PMID- 14674509
TI  - Determination of the moisture content of bromobutyl rubber stoppers as a function
      of processing: implications for the stability of lyophilized products.
AB  - The purpose of the present study is to apply and contrast several analytical
      techniques to understand the change in moisture content of 20 mm diameter
      bromobutyl rubber stoppers as a function of typical stopper processing
      conditions. Three separate methods were examined and Karl-Fischer titration and
      techniques based on capacitance measurements at a thin-film sensor were found to
      provide comparable results. Stopper moisture levels were examined in stoppers:
      (i) as received from the manufacturer, (ii) following steam sterilization, (iii)
      as a function of various drying cycles, and (iv) during simulated hold conditions
      prior to use. Finally, the transfer of moisture from stopper to an actual product
      is examined on storage and general agreement observed between stopper drying
      conditions and cake moisture levels.

PMID- 14674508
TI  - The use of stratefied sampling of blend and dosage units to demonstrate adequacy
      of mix for powder blends.
AB  - In response to concerns expressed by applicants regarding inconsistent policies
      in establishing blend uniformity acceptance criteria to demonstrate adequacy of
      mix, the FDA Office of Generic Drugs (OGD) issued the draft document Guidance for
      Industry, ANDAs: Blend Uniformity Analysis (August 1999). Both generic and
      innovator pharmaceutical companies raised a number of concerns following the
      publication of this document. As a result, the Product Quality Research Institute
      (PQRI) Blend Uniformity Working Group (BUWG) was established in February 2000.
      One of the primary goals of this group was to draft a scientifically based
      alternative to the OGD document. The resulting recommendation addresses both FDA
      and industry concerns by substantially enhancing product quality assurance
      without increasing regulatory burden. The PQRI BUWG recommends that these blend
      and dosage unit uniformity requirements be administered uniformly throughout the
      industry. PQRI submitted the following recommendation to the FDA on December 31,
      2002, providing the Agency with an alternative strategy to consider when drafting
      future regulatory policy to assess blend and dosage unit uniformity.

PMID- 14674510
TI  - Considerations in sterile filtration. Part II: the sterilizing filter and its
      organism challenge: a critique of regulatory standards.

PMID- 14674511
TI  - Nomenclature associated with chemical characterization of and compatibility
      evaluations for medical product delivery systems.
AB  - Delivery systems are used to store, contain, and/or administer liquid
      pharmaceutical products. Gaining an understanding of the chemical composition of
      such a delivery system is necessary with respect to effective system development,
      registration, and production. Additionally, the ability of the delivery system to
      impact the chemical composition of the contacted product may define the safety
      and/or efficacy of the product. Assessing the compatibility of the delivery
      system and the product is thus both necessary and desirable. The nomenclature
      associated with compatibility assessments has not been standardized, oftimes
      leading to conflicting or confusing information. This manuscript puts forth a
      nomenclature which classifies those chemical entities which participate in the
      system/product interaction and delineates the various extraction strategies which
      may be used in compatibility assessments.

PMID- 14674512
TI  - Synthesis and antibacterial evaluation of 4-substituted-2-phenyl-1-p-tolyl-4
      thiomethyl-1,3-diazabuta-1,3-dienes: a novel class of antibacterial agents.
AB  - A series of novel-2-phenyl-1-p-tolyl-4-thiomethyl-1,3-diazabuta-1,3-dienes
      compounds (5a-5e) possessing morpholino, diethyl amino, pyrrolidino, piperidino
      and 2-aminopyridino groups respectively at C-4 were prepared by reaction of alpha
      aryliminobenzyl isothiocyanates with secondary amines and S-alklyation of the
      resultant thioureas with aqueous potassium hydroxide. The isothiocyanates were
      obtained from easily available starting materials. These 1,3-diazabuta-1,3-dienes
      were obtained in pure form after recrystallization and their structures were
      established by analytical and spectral data. The synthesized compounds were
      screened for their antibacterial activity and some of them were found to exhibit
      significant antibacterial activity.

PMID- 14674514
TI  - Development of a new concept for time/pressure filling.

PMID- 14674513
TI  - Modern cleanroom clothing systems: people as a contamination source.
AB  - Today, clothing and clothing systems for cleanrooms are mainly tested with regard
      to material properties such as particle generation, particle filtration, and
      resistance to wear. The dispersal chamber or "body-box" has been used for
      studying the protective efficacy of clothing systems in use, for example by
      Hoborn in 1981 (1) and Whyte and Bailey in 1985. A modified dispersal chamber has
      recently been installed at KTH. Tests and comparative studies have been performed
      in the dispersal chamber on selected clothing systems. The latest tests have been
      performed in two parts. In Part 1, each person performed 12 sequences dressed in
      new, modern cleanroom clothing systems with small variations, such as with and
      without goggles, different face masks, and different sizes of hoods. In Part 2,
      each person performed six test sequences with new, modern cleanroom clothing
      systems with variations in fabrics, and as a comparison, two sequences with
      pharmaceutical clothing system and surgical clothing system, respectively. The
      results are given in total number of airborne particles (> or = 0.5 microm per
      cubic meter) and airborne aerobic CFU per cubic meter. Statistical evaluations of
      the results have been performed. The source strengths of the contamination source
      people wearing modern cleanroom clothing systems have been estimated.

PMID- 14674515
TI  - Overview of the forthcoming PDA task force report on the inspection for visible
      particles in parenteral products: practical answers for present problems.

PMID- 14674516
TI  - Enhancing phytoextraction: the effect of chemical soil manipulation on mobility,
      plant accumulation, and leaching of heavy metals.
AB  - For heavy metal-contaminated agricultural land, low-cost, plant-based
      phytoextraction measures can be a key element for a new land management strategy.
      When agents are applied into the soil, the solubility of heavy metals and their
      subsequent accumulation by plants can be increased, and, therefore,
      phytoextraction enhanced. An overview is given of the state of the art of
      enhancing heavy metal solubility in soils, increasing the heavy metal
      accumulation of several high-biomass-yielding and metal-tolerant plants, and the
      effect of these measures on the risk of heavy metal leaching. Several organic as
      well as inorganic agents can effectively and specifically increase solubility
      and, therefore, accumulation of heavy metals by several plant species. Crops like
      willow (Salix viminalis L.), Indian mustard [Brassica juncea (L.) Czern.], corn
      (Zea mays L.), and sunflower (Helianthus annuus L.) show high tolerance to heavy
      metals and are, therefore, to a certain extent able to use the surpluses that
      originate from soil manipulation. More than 100-fold increases of lead
      concentrations in the biomass of crops were reported, when
      ethylenediaminetetraacetic acid (EDTA) was applied to contaminated soils. Uranium
      concentrations could be strongly increased when citric acid was applied. Cadmium
      and zinc concentrations could be enhanced by inorganic agents like elemental
      sulfur or ammonium sulfate. However, leaching of heavy metals due to increased
      mobility in soils cannot be excluded. Thus, implementation on the field scale
      must consider measures to minimize leaching. So, the application of more than 1 g
      EDTA kg(-1) becomes inefficient as lead concentration in crops is not enhanced
      and leaching rate increases. Moreover, for large-scale applications, agricultural
      measures as placement of agents, dosage splitting, the kind and amount of agents
      applied, and the soil properties are important factors governing plant growth,
      heavy metal concentrations, and leaching rates. Effective prevention of leaching,
      breeding of new plant material, and use of the contaminated biomass (e.g., as
      biofuels) will be crucial for the acceptance and the economic breakthrough of
      enhanced phytoextraction.

PMID- 14674517
TI  - Phosphorus restrictions for land application of biosolids: current status and
      future trends.
AB  - The application of biosolids (sewage sludge) to agricultural soils provides P in
      excess of crop needs when applied to meet the N needs of most agronomic crops.
      These overapplications can result in the buildup of P in soils to values well
      above those needed for optimum crop yields and also may increase risk of P losses
      to surface and ground waters. Because of concerns regarding the influence of P on
      water quality in the USA, many state and federal agencies now recommend or
      require P-based nutrient management plans for animal manures. Similar actions are
      now under consideration for the land application of biosolids. We reviewed the
      literature on this subject and conducted a national survey to determine if states
      had restrictions on P levels in biosolids-amended soils. The literature review
      indicates that while the current N-based approach to biosolids management does
      result in increases of soil P, some properties of biosolids may mitigate the
      environmental risk to water quality associated with land application of P in
      biosolids. Results of the survey showed that 24 states have regulations or
      guidelines that can be imposed to restrict land application of biosolids based on
      P. Many of these states use numerical thresholds for P in biosolids-amended soils
      that are based on soil test phosphorus (STP) values that are much greater than
      the values considered to be agronomically beneficial. We suggest there is the
      need for a comprehensive environmental risk assessment of biosolids P. If risk
      assessment suggests the need for regulation of biosolids application, we suggest
      regulations be based on the P Site Index (PSI), which is the method being used by
      most states for animal manure management.

PMID- 14674518
TI  - Spatial variability of nitrous oxide emissions and their soil-related determining
      factors in an agricultural field.
AB  - To evaluate spatial variability of nitrous oxide (N2O) emissions and to elucidate
      their determining factors on a field-scale basis, N2O fluxes and various soil
      properties were evaluated in a 100- x 100-m onion (Allium cepa L.) field. Nitrous
      oxide fluxes were determined by a closed chamber method from the one-hundred 10-
      x 10-m plots. Physical (e.g., bulk density and water content), chemical (e.g.,
      total N and pH), and biological (e.g., microbial biomass C and N) properties were
      determined from surface soil samples (0-0.1 m) of each plot. Geostatistical
      analysis was performed to examine spatial variability of both N2O fluxes and soil
      properties. Multivariate analysis was also conducted to elucidate relationships
      between soil properties and observed fluxes. Nitrous oxide fluxes were highly
      variable (average 331 microg N m(-2) h(-1), CV 217%) and were log-normally
      distributed. Log-transformed N2O fluxes had moderate spatial dependence with a
      range of >75 m. High N2O fluxes were observed at sites with relatively low
      elevation. Multivariate analysis indicated that an organic matter factor and a pH
      factor of the principal component analysis were the main soil-related determining
      factors of log-transformed N2O fluxes. By combining multivariate analysis with
      geostatistics, a map of predicted N2O fluxes closely matched the spatial pattern
      of measured fluxes. The regression equation based on the soil properties
      explained 56% of the spatially structured variation of the log-transformed N2O
      fluxes. Site-specific management to regulate organic matter content and water
      status of a soil could be a promising means of reducing N2O emissions from
      agricultural fields.

PMID- 14674519
TI  - Methane emissions of rice increased by elevated carbon dioxide and temperature.
AB  - Methane (CH4) effluxes by paddy-culture rice (Oryza sativa L.) contribute about
      16% of the total anthropogenic emissions. Since radiative forcing of CH4 at
      current atmospheric concentrations is 21 times greater on a per mole basis than
      that of carbon dioxide (CO2), it is imperative that the impact of global change
      on rice CH4 emissions be evaluated. Rice (cv. IR72) was planted in sunlit, closed
      circulation, controlled-environment chambers in which CH4 efflux densities were
      measured daily. The CO2 concentration was maintained at either 330 or 660
      micromol mol(-1). Air temperatures were controlled to daily maxima and minima of
      32/23, 35/26, and 38/29 degrees C at each CO2 treatment. Emissions of CH4 each
      day were determined during a 4-h period after venting and resealing the chambers
      at 0800 h. Diurnal CH4 effluxes on 77, 98, and 119 d after planting (DAP) were
      obtained similarly at 4-h intervals. Emissions over four-plant hills and over
      flooded bare soil were measured at 53, 63, and 100 DAP. Emissions were negligible
      before 40 DAP. Thereafter, emissions were observed first in high-CO2, high
      temperature treatments and reached a sustained maximum efflux density of about 7
      mg m(-2) h(-1) (0.17 g m(-2) d(-1)) near the end of the growing season. Total
      seasonal CH4 emission was fourfold greater for high-CO2, high-temperature
      treatments than for the low-CO2, low-temperature treatment, probably due to more
      root sloughing or exudates, since about sixfold more acetate was found in the
      soil at 71 DAP. Both rising CO2 and increasing temperatures could lead to a
      positive feedback on global warming by increasing the emissions of CH4 from rice.

PMID- 14674520
TI  - The effect of five forage species on transport and transformation of atrazine and
      isoxaflutole (balance) in lysimeter leachate.
AB  - A field lysimeter study with bare ground and five different ground covers was
      established to evaluate the effect of forage grasses on the fate and transport of
      two herbicides in leachate. The herbicides were atrazine (ATR; 2-chloro-4
      ethylamino-6-isopropylamino-1,3,5-triazine) and isoxaflutole [IXF; 5-cyclopropyl
      4-(2-methylsulfonyl-4-trifluormethyl-benzoyl)isoxazole], which has the commercial
      name Balance (Aventis Crop Science, Strasbourg, France). The ground covers
      included orchardgrass (Dactylis glomerata L.), smooth bromegrass (Bromus inermis
      Leyss.), tall fescue (Festuca arundinacea Schreb.), timothy (Phleum pratense L.),
      and switchgrass (Panicum virgatum L.). The results suggested that the total IXF
      (parent + metabolites) showed higher mobility than ATR and its metabolites.
      Differences in the timing of transport reflected the rapid degradation of IXF to
      the more soluble, stable, and biologically active diketonitrile (DKN) metabolite
      in the system. Although grass treatments did not promote the hydrolysis of DKN,
      they significantly reduced its transport in the leachate through enhanced
      evapotranspiration. Grass treatments significantly enhanced ATR degradation in
      the leachates and soils, especially through N dealkylation, but they did not
      reduce total ATR transported in the leachate. Leachate from the orchardgrass
      lysimeters contained the highest proportion of ATR metabolites (64.2%). Timothy
      and smooth bromegrass treatments also displayed a significant increase in ATR
      metabolites in leachate. Grass-treated lysimeters showed higher microbial biomass
      carbon than bare ground. For ATR treatments, the proportion of metabolites in the
      leachate strongly correlated with the elevated soil microbial biomass carbon in
      forage treatments. In contrast, DKN degradation was poorly correlated with soil
      microbial biomass carbon, suggesting that DKN degradation is an abiotic process.

PMID- 14674521
TI  - Role of mycorrhizal fungi and phosphorus in the arsenic tolerance of basin
      wildrye.
AB  - Revegetation of arsenic (As)-rich mine spoils is often impeded by the lack of
      plant species tolerant of high As concentrations and low nutrient availability.
      Basin wildrye [Leymus cinereus (Scribner & Merr.) A. Love] has been observed to
      establish naturally in soils with elevated As content and thus may be useful for
      the stabilization of As-contaminated soils. An experiment was conducted to
      evaluate how variable phosphorus (P) concentrations and inoculation with site
      specific arbuscular mycorrhizal fungi influence As tolerance of basin wildrye.
      Basin wildrye was grown in sterile sand in the greenhouse for 16 weeks. Pots of
      sterile sand were amended to create one of four rates of As (0, 3, 15, or 50 mg
      As kg(-1)), two rates of P (3 or 15 mg P kg(-1)), and +/-mycorrhizal inoculation
      in a 2 x 4 x 2 factorial arrangement. After 16 weeks of growth, plants were
      harvested, shoots and roots thoroughly washed, and the tissue analyzed for total
      shoot biomass, total root and shoot As and P concentrations, and degree of
      mycorrhizal infection. Basin wildrye was found to be tolerant of high As
      concentrations allowing for vigorous plant growth at application levels of 3 or
      15 mg As kg(-1). Arsenic was sequestered in the roots, with 30 to 50 times more
      As in the roots than shoots under low P conditions. Mycorrhizal infection did not
      confer As tolerance in basin wildrye nor did mycorrhizal fungi influence biomass
      production. Phosphorus concentrations of 15 mg kg(-1) effectively inhibited As
      accumulation in basin wildrye. Basin wildrye has the potential to be used for
      stabilization of As-rich soils while minimizing exposure to grazing animals
      following reclamation.

PMID- 14674522
TI  - Contribution of particulate phosphorus to runoff phosphorus bioavailability.
AB  - Runoff P associated with eroded soil is partly solubilized in receiving waters
      and contributes to eutrophication, but the significance of particulate phosphorus
      (PP) in the eutrophying P load is debatable. We assessed losses of bioavailable P
      fractions in field runoff from fine-textured soils (Cryaquepts). Surface runoff
      at four sites and drain-flow at two of them was sampled. In addition to dissolved
      molybdate-reactive phosphorus (DRP) losses, two estimates of bioavailable PP
      losses were made: (i) desorbable PP, assessed by anion exchange resin-extraction
      (AER-PP) and (ii) redox-sensitive PP, assessed by extraction with bicarbonate and
      dithionite (BD-PP). Annual losses of BD-PP and AER-PP were derived from the
      relationships (R2 = 0.77-0.96) between PP and these P forms. Losses of BD-PP in
      surface runoff (94-1340 g ha(-1)) were typically threefold to fivefold those of
      DRP (29-510 kg ha(-1)) or AER-PP (13-270 g ha(-1)). Where monitored, drainflow P
      losses were substantial, at one of the sites even far greater than those via the
      surface pathway. Typical runoff DRP concentration at the site with the highest
      Olsen-P status (69-82 mg kg(-1)) was about 10-fold that at the site with the
      lowest Olsen P (31-45 mg kg(-1)), whereas the difference in AER-PP per mass unit
      of sediment was only threefold, and that of BD-PP 2.5-fold. Bioavailable P losses
      were greatly influenced by PP runoff, especially so on soils with a moderate P
      status that produced runoff with a relatively low DRP concentration.

PMID- 14674523
TI  - Effect of soil properties on saturated and unsaturated virus transport through
      columns.
AB  - Viruses from contaminant sources can be transported through porous media to
      drinking water wells. The objective of this study was to investigate inactivation
      and sorption of viruses during saturated and unsaturated transport in different
      soils. Bacteriophages phiX174 and MS-2, and Br- tracer in a phosphate-buffered
      saline solution were introduced into saturated and unsaturated soil columns as a
      step function under constant flow rate and hydraulic conditions. Results showed
      that significantly greater virus removal occurred in the unsaturated columns than
      in the saturated columns in the two soils containing high metal oxides content.
      However, the increase in virus retention under unsaturated conditions was not
      significant in two other soils having high phosphorus and calcium contents and
      high pH, and in another soil with high organic matter content. The results imply
      that the extent of water content effect on inactivation and sorption of viruses
      can range from significant to minimal depending on the properties of the
      transport medium. We found that the presence of in situ metal oxides was a
      significant factor responsible for virus sorption and inactivation. Therefore,
      soils with high metal oxides content may have the potential to be used as
      hydrological barriers in preventing microbial contamination in the subsurface
      environments. We also found that the water content effect on virus removal and
      inactivation strongly depended on solid properties of the testing medium.

PMID- 14674524
TI  - Modeling flow and nitrate fate at catchment scale in Brittany (France).
AB  - In the intensive pig-farming (Sus scrofa) area of Brittany (western France), many
      surface and subsurface water resources are contaminated by nitrate (NO3) with
      concentrations that chronically exceed the European Community 50 mg L(-1)
      drinking standard. To ensure sustainable water supply, the fate of NO3 must be
      considered in both surface water and ground water. The fate of N was investigated
      in a Britain catchment, the Coet-Dan watershed, with an integrated management
      tool: the hydrological SWAT model coupled with the ground water model MODFLOW,
      and its companion contaminant and solute transport model MT3DMS. The model was
      validated with respect to water quantity during a 6-yr period and for the NO3
      concentration during a 44-mo period, at two gauging stations in the catchment.
      The coupled models reproduced accurately the measurements. At the basin outlet,
      the Nash-Sutcliffe coefficients were 0.88 for monthly flow for the entire period
      and 0.87 for monthly N load. Alternative scenarios were simulated and showed
      potential benefits of decreasing manure application from 210 to 170 kg N ha(-1)
      as required by the European Commission Nitrates Directive.

PMID- 14674525
TI  - Mineralogical characteristics and transformations during long-term operation of a
      zerovalent iron reactive barrier.
AB  - Design and operation of Fe0 permeable reactive barriers (PRBs) can be improved by
      understanding the long-term mineralogical transformations that occur within PRBs.
      Changes in mineral precipitates, cementation, and corrosion of Fe0 filings within
      an in situ pilot-scale PRB were examined after the first 30 months of operation
      and compared with results of a previous study of the PRB conducted 15 months
      earlier using X-ray diffraction and scanning electron microscopy employing energy
      dispersive X-ray and backscatter electron analyses. Iron (oxy)hydroxides,
      aragonite, and maghemite and/or magnetite occurred throughout the cores collected
      30 mo after installation. Goethite, lepidocrocite, mackinawite, aragonite,
      calcite, and siderite were associated with oxidized and cemented areas, while
      green rusts were detected in more reduced zones. Basic differences from our last
      detailed investigation include (i) mackinawite crystallized from amorphous FeS,
      (ii) aragonite transformed into calcite, (iii) akaganeite transformed to goethite
      and lepidocrocite, (iv) iron (oxy)hydroxides and calcium and iron carbonate
      minerals increased, (v) cementation was greater in the more recent study, and
      (vi) oxidation, corrosion, and disintegration of Fe0 filings were greater,
      especially in cemented areas, in the more recent study. If the degree of
      corrosion and cementation that was observed from 15 to 30 mo after installation
      continues, certain portions of the PRB (i.e., up-gradient entrance of the ground
      water to the Fe0 section of the PRB) may last less than five more years, thus
      reducing the effectiveness of the PRB to mitigate contaminants.

PMID- 14674526
TI  - Sorption of MS2 bacteriophage to layered double hydroxides: effects of reaction
      time, pH, and competing anions.
AB  - Batch sorption and column breakthrough studies were conducted to investigate the
      potential of layered double hydroxides (LDHs) to remove bacteriophage MS2 from
      contaminated waters. All four of the LDHs evaluated in this study had very high
      retention capacities for MS2. Sorption results showed that MS2 could be
      completely removed from 5.2 x 10(2) plaque-forming units (pfu)/mL solution by Mg
      Al LDH 2 (i.e., 2:1 Mg to Al ratio LDH), with the highest sorption capacity
      observed in this study of 1.51 x 10(10) pfu/g. Attachment of MS2 to LDHs was a
      rapid process and reached quasi-equilibrium after a 1-h reaction time. Within the
      pH range studied (pH 4-9), Mg-Al LDH 2 showed high sorption potential for MS2 at
      all pH values but sorption decreased slightly with increasing solution pH.
      Background solution anions influenced virus sorption, with SO4(2-) and HPO4(2-)
      decreasing sorption significantly whereas the presence of NO3- had little effect
      on the attachment of MS2 to Mg-Al LDH 2. The addition of another virus (phiX174)
      only caused a slight decrease in the retention of MS2 by Mg-Al LDH 2, suggesting
      that there was insignificant competitive sorption between MS2 and phiX174 on LDH
      surfaces. Results from column experiments indicate that there was no MS2
      breakthrough from columns packed with Mg-Al LDH 2-coated sand, suggesting
      complete MS2 retention at the virus concentration tested. The high mass recovery
      by beef extract solution revealed that the removal of viruses by the LDH was due
      to sorption of MS2 to LDH surfaces, rather than inactivation.

PMID- 14674527
TI  - Prediction of trace element mobility in contaminated soils by sequential
      extraction.
AB  - The modified three-step sequential extraction procedure proposed by the Community
      Bureau of Reference (or Bureau Communautaire de Reference, BCR) was used to
      predict trace element mobility in soils affected by an accidental spill
      comprising arsenopyrite- and heavy metal-enriched sludge particles and acid waste
      waters. The procedure was used to obtain the distribution of both the major (Al,
      Ca, Fe, Mg, and Mn) and trace elements (As, Bi, Cd, Cu, Pb, Tl, and Zn) in 13
      soils of contrasting properties with various levels of contamination and in the
      sludge itself. The distributions of the major elements enabled us to confirm the
      main soil fractions solubilized in each of the three steps, and, in turn, to
      detect the presence of pyritic sludge particles by the high Fe extractability
      obtained in the third step. Cadmium was identified as being the most mobile of
      the elements, having the highest extractability in the first step, followed by Zn
      and Cu, Lead, Tl, Bi, and As were shown to be poorly mobile or nonmobile. In the
      case of some of the trace elements, the residual fractions decreased at higher
      levels of contamination, which was attributed to the anthropogenic contributions
      to the polluted samples. Comparison with soil-plant transfer factors, calculated
      in plants growing in the affected area, indicated that a relative sequence of
      trace element mobility was well predicted from data of the first step.

PMID- 14674528
TI  - Temperature and microbial activity effects on trace element leaching from
      metalliferous peats.
AB  - Due to geochemical processes, peat soils often have elevated concentrations of
      trace elements, which are gradually released following drainage for agriculture.
      Our objectives were to use incubation temperatures to vary microbial activity in
      two metalliferous peats (M7 acidic peat and M3 neutral peat) from the Elba, New
      York region, and to use periodic leaching to assess the extent of trace element
      release from these soils. Dried soils were mixed with glass beads to maintain
      aeration, moistened, and incubated at 4, 16, 28, and 37 degrees C in 10-cm
      diameter x 8-cm-tall columns. Five incubation-leaching cycles were performed,
      each consisting of 7.3 d of incubation (28 d for the final cycle) followed by 16
      h of leaching with synthetic acid rain at 2.5 mm h(-1). Microbial activity was
      determined initially and after the final leaching by measuring C mineralization
      following glucose stimulation. Cumulative respiration results were ranked 28 > 16
      > 4 > 37 degrees C, with M7 acidic peat respiration values greater than M3
      neutral peat at each temperature. Initial leachate pH levels were between 2 and
      4, with acidification less pronounced and shorter-lived for the M3 peat. Leachate
      S, dissolved organic carbon (DOC), NO3-N, and trace elements declined with
      successive leachings (rebounding slightly in the final M3 leachate), with
      concentrations typically greater in the M7 leachate. Elemental losses followed
      the same general ranking (28 > 16 > 4 > 37 degrees C); losses at 28 degrees C
      were 15 to 22% for As, Cd, Ni, and Zn from the M7 peat; losses from M3 were
      comparable only for Cu (1%) and Ni (19%). The correlation of respiration with S,
      DOC, and trace elements losses indicates that microbial processes mediated the
      release of trace elements in both peat soils. Neutral M3 peat pH levels limited
      losses of most analytes.

PMID- 14674529
TI  - Light-catalyzed chromium(VI) reduction by organic compounds and soil minerals.
AB  - Detoxification of Cr(VI) through reduction has been considered an effective
      method for reclaiming Cr-contaminated soil, sediment, and waste water. Organic
      matter is widely distributed in soil and aquatic systems; however, low Cr(VI)
      reduction rates inhibit the adoption of Cr reduction technologies by industry.
      Scientists have been aware of Cr(VI) reduction catalyzed by soil minerals;
      however, most of the studies focused on using semiconductors as catalysts with UV
      irradiation to accelerate the redox reactions. The objective of this study was to
      evaluate the rates of Cr(VI) reduction by fluorescence light in the presence of
      organic materials with or without specific soil minerals. Experimental results
      showed that dissolved organic compounds reduced Cr(VI) slowly under laboratory
      light; however, Cr(VI) reduction was greatly enhanced when growth chamber light
      was applied. Low photon flux (i.e., laboratory light) only enhanced Cr(VI)
      reduction by organics when Fe(III) was also present, because the Fe(II)-Fe(III)
      redox couple accelerated electron transfer and decreased electrostatic repulsion
      between reactants. Laboratory light was required to initiate Cr(VI) reduction
      catalyzed by TiO2; nonetheless, light-catalyzed Cr(VI) reduction by smectite and
      ferrihydrite could occur only when greater light energy was provided with a
      growth chamber light. Our results suggest a potential pathway for Cr(VI)
      reduction using naturally occurring organic compounds and colloids in acidic
      water systems or in surface soils when light is available.

PMID- 14674530
TI  - Are methylmercury concentrations in the wetlands of Kejimkujik National Park,
      Nova Scotia, Canada, dependent on geology?
AB  - In the relatively pristine ecosystem in Kejimkujik Park, Nova Scotia,
      methylmercury (MeHg) concentrations in loons, Gavia immer, are among the highest
      recorded anywhere in the world. This study investigated the influence of bedrock
      lithology on MeHg concentrations in wetlands. Twenty-five different wetland field
      sites were sampled over four different bedrock lithologies; Kejimkujik
      monzogranite, black sulfidic slate, gray slate, and greywacke. Soil samples were
      analyzed for ethylmercury (EtHg), MeHg, total Hg, acid-volatile sulfides (AVS),
      organic matter, and water content as well as the biological parameters, mercury
      methyltransferase (HgMT) activity, sulfate reduction rates, fatty acid methyl
      ester (FAME) composition, and acidity. Methylmercury concentrations in the
      wetlands were highly dependent (P < 0.08) on lithology with no significant
      difference between bogs, fens, and swamps. Methylmercury concentrations in
      wetland soils developed on Kejimkujik monzogranite averaged 900 ng kg(-1)
      compared with only 300 ng kg(-1) in wetland soils developed on black sulfidic
      slate. Fatty acid methyl ester composition was also lithologically dependent (P <
      0.001) with biomarkers for Desulfobulbus spp. discriminating between sites
      containing high and low MeHg concentrations. Levels of MeHg in wetlands were
      predicted mainly (41% of the sum of squares) by HgMT activity that differed (P <
      0.009) between wetlands, with activity in bogs almost three times that present in
      swamps. Wetland MeHg concentrations are highly dependent on the lithology on
      which they have developed for largely biological reasons.

PMID- 14674531
TI  - Copper, zinc, and arsenic in soil surrounding Douglas-fir poles treated with
      ammoniacal copper zinc arsenate (ACZA).
AB  - The levels of copper, zinc, and arsenic in soil surrounding Douglas-fir
      [Pseudotsuga menziesii (Mirb.) Franco] utility poles treated with ammoniacal
      copper zinc arsenate (ACZA) were investigated at sites in Florida, Virginia, and
      New York. Copper levels were elevated near the poles and declined with both
      horizontal distance away from the pole and depth beneath the soil surface. Zinc
      levels were also elevated next to the poles, but the levels declined more slowly
      than did those of copper. Arsenic levels were elevated in soil immediately next
      to the poles but declined to near background levels farther away. The results
      indicate that metals can leach from ACZA-treated poles, but do not migrate far in
      the soil, and thus the levels decline sharply with distance from the poles.

PMID- 14674532
TI  - Compartmentalization of metals within the diverse colloidal matrices comprising
      activated sludge microbial flocs.
AB  - Activated sludge floc from a wastewater treatment system was characterized, with
      regard to principal structural, chemical, and microbiological components and
      properties, in relation to contaminant-colloid associations and settling.
      Multiscale analytical microscopies, in conjunction with multimethod sample
      preparations, were used correlatively to characterize diverse colloidal matrices
      within microbial floc. Transmission electron microscopy, in conjunction with
      energy dispersive spectroscopy (EDS), revealed specific associations of
      contaminant heavy metals with individual bacterial cells and with extracellular
      polymeric substances (EPS). Floc structure was mapped from the level of gross
      morphology down to the nano-scale, and flocs were described with respect to
      settling properties, size, shape, density, porosity, bound water content, and EPS
      chemical composition; gross surface properties were also measured for correlation
      with principal floc features. Compartmentalization results based on 171 EDS
      analyses and representative high-resolution images showed that nano-scale
      agglomerations of (i) silver (100%) and (ii) zinc (91%) were confined almost
      entirely to EPS matrices while (iii) Pb (100%) was confined to intracellular
      granules and (iv) aluminum was partitioned between EPS matrices (41%) and
      intracellular matrices (59%). The results suggest that engineered changes in
      microbial physiology and/or in macromolecular EPS composition may influence metal
      removal efficiencies.

PMID- 14674533
TI  - Major and trace elements of selected pedons in the USA.
AB  - Few studies of soil geochemistry over large geographic areas exist, especially
      studies encompassing data from major pedogenic horizons that evaluate both native
      concentrations of elements and anthropogenically contaminated soils. In this
      study, pedons (n = 486) were analyzed for trace (Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb,
      Zn) and major (Al, Ca, Fe, K, Mg, Na, P, Si, Ti, Zr) elements, as well as other
      soil properties. The objectives were to (i) determine the concentration range of
      selected elements in a variety of U.S. soils with and without known anthropogenic
      additions, (ii) illustrate the association of elemental source and content by
      assessing trace elemental content for several selected pedons, and (iii) evaluate
      relationships among and between elements and other soil properties. Trace element
      concentrations in the non-anthropogenic dataset (NAD) were in the order Mn > (Zn,
      Cr, Ni, Cu) > (Pb, Co) > (Cd, Hg), with greatest mean total concentrations for
      the Andisol order. Geometric means by horizon indicate that trace elements are
      concentrated in surface and/or B horizons over C horizons. Median values for
      trace elements are significantly higher in surface horizons of the anthropogenic
      dataset (AD) over the NAD. Total Al, Fe, cation exchange capacity (CEC), organic
      C, pH, and clay exhibit significant correlations (0.56, 0.74, 0.50, 0.31, 0.16,
      and 0.30, respectively) with total trace element concentrations of all horizons
      of the NAD. Manganese shows the best inter-element correlation (0.33) with these
      associated total concentrations. Total Fe has one of the strongest relationships,
      explaining 55 and 30% of the variation in total trace element concentrations for
      all horizons in the NAD and AD, respectively.

PMID- 14674534
TI  - Influence of organic matter decomposition on soluble carbon and its copper
      binding capacity.
AB  - Bulk and low molecular weight (LMW) (<1 kDa) water-extractable carbon were
      collected from fresh and microbially degraded wheat straw (Triticum aestivum L.)
      and crimson clover (Trifolium incarnatum L.) residues to monitor early-stage
      humification over an 8-wk incubation. Copper complexation parameters were
      determined for both bulk and LMW water-extractable C for both plant materials in
      a separate 1-wk incubation. Humification progressed through increasing molar
      absorptivity (A285) and phenolic and total acidity (TA), and through an increase
      in average molecular size and degree of polymerization as determined by
      ultrafiltration and changes in fluorescence peak locations. Such dynamic
      transformations demonstrate that while humification is a bulk property, with C
      breakdown and stabilization occurring simultaneously and continuously in soil,
      its early stages can be effectively monitored for fresh plant residues.
      Significant changes consistently occurred during the first 7 d of the incubation
      and were more pronounced for LMW fractions than bulk extracts. For both residues,
      water-extractable C extracted initially and following a 7-d incubation desorbed
      and complexed 0.11 to 0.55 mmol resin-bound Cu g(-1) C. Low molecular weight
      water-extractable C generated the higher values within this range, and values
      increased consistently following incubation. Potential concerns regarding LMW
      soluble Cu complexes include percolation through soils or runoff into adjacent
      water bodies as well as effects on plant root development.

PMID- 14674535
TI  - Earthworm additions affect leachate production and nitrogen losses in typical
      midwestern agroecosystems.
AB  - Earthworms affect soil structure and the movement of agrochemicals. Yet, there
      have been few field-scale studies that quantify the effect of earthworms on
      dissolved nitrogen fluxes in agroecosystems. We investigated the influence of
      semi-annual earthworm additions on leachate production and quality in different
      row crop agroecosystems. Chisel-till corn (Zea mays L.)-soybean [Glycine max (L.)
      Merr.] rotation (CT) and ridge-till corn-soybean-wheat (Triticum aestivum L.)
      rotation (RT) plots were arranged in a complete randomized block design (n = 3)
      with earthworm treatments (addition and ambient) as subplots where zero-tension
      lysimeters were placed 45 cm below ground. We assessed earthworm populations semi
      annually and collected leachate biweekly over a three-year period and determined
      leachate volume and concentrations of total inorganic nitrogen (TIN) and
      dissolved organic nitrogen (DON). Abundance of deep-burrowing earthworms was
      increased in addition treatments over ambient and for both agroecosystems.
      Leachate loss was similar among agroecosystems, but earthworm additions increased
      leachate production in the range of 4.5 to 45.2% above ambient in CT cropping.
      Although leachate TIN and DON concentrations were generally similar between
      agroecosystems or earthworm treatments, transport of TIN was significantly
      increased in addition treatments over ambient in CT cropping due to increased
      leachate volume. Losses of total nitrogen in leachate loadings were up to
      approximately 10% of agroecosystem N inputs. The coincidence of (i) soluble N
      production and availability and (ii) preferential leaching pathways formed by
      deep-burrowing earthworms thereby increased N losses from the CT agroecosystem at
      the 45-cm depth. Processing of N compounds and transport in soil water from RT
      cropping were more affected by management phase and largely independent of
      earthworm activity.

PMID- 14674536
TI  - Soil phosphorus, management practices, and their relationship to phosphorus
      delivery in the Iowa Clear Lake agricultural watershed.
AB  - Clear Lake is on Iowa's list of impaired water bodies because of high P
      concentration. This study assessed soil-test phosphorus (STP), management
      practices, and P loads from its agricultural watershed. Management practice
      histories and STP for eight basins were surveyed in 1999. Soil samples (15-cm
      depth) were analyzed for STP with agronomic [Bray P1 (BP), Olsen (OP), Mehlich 3
      (M3P) and environmental [iron oxide-impregnated paper (FeP) and water extraction
      (WP)] tests. Total phosphorus (TP) concentrations in water discharge from five
      basins were measured during two years, and TP loads were measured for two basins.
      The agronomic P tests showed that 46 to 83% (depending on the test) of the area
      tested above optimum for crops. Correlations among tests were high for OP, M3P,
      and FeP (r > 0.96) and lower for BP and WP (r = 0.88-0.93). Moldboard- and chisel
      plow tillage predominated (82% of the area). Applied P (mainly fertilizer)
      averaged 15 kg P ha(-1) yr(-1), and 40% of the high-testing area (M3P test) was
      being fertilized. The mean annual water TP concentration across five basins was
      275 to 474 microg L(-1). The two-year mean TP loads for the two gauged basins
      were 1504 and 1510 g P ha(-1) yr(-1). Water TP concentration increased linearly
      with increasing STP. Relationships were stronger for M3P and FeP (R2 = 0.96-0.97
      for annual means and 0.77-0.79 for storm-flow events) than for BP or WP (R2 =
      0.88-0.91 and 0.59-0.69, respectively). Improving P and soil conservation
      practices in high-testing areas could reduce P loads to the lake.

PMID- 14674537
TI  - Pulsed redistribution of a contaminant following forest fire: cesium-137 in
      runoff.
AB  - Of the natural processes that concentrate dispersed environmental contaminants,
      landscape fire stands out as having potential to rapidly concentrate contaminants
      and accelerate their redistribution. This study used rainfall simulation methods
      to quantify changes in concentration of a widely dispersed environmental
      contaminant (global fallout 137Cs) in soils and surface water runoff following a
      major forest fire at Los Alamos, New Mexico, USA. The 137Cs concentrations at the
      ground surface increased up to 40 times higher in ash deposits and three times
      higher for the topmost 50 mm of soil compared with pre-fire soils. Average
      redistribution rates were about one order of magnitude greater for burned plots,
      5.96 KBq ha(-1) mm(-1) rainfall, compared with unburned plots, 0.55 KBq ha(-1)
      mm(-1) rainfall. The greatest surface water transport of 137Cs, 11.6 KBq ha(-1)
      mm(-1), occurred at the plot with the greatest amount of ground cover removal
      (80% bare soil) following fire. Concentration increases of 137Cs occurred during
      surface water erosion, resulting in enrichment of 137Cs levels in sediments by
      factors of 1.4 to 2.9 compared with parent soils. The elevated concentrations in
      runoff declined rapidly with time and cumulative precipitation occurrence and
      approached pre-fire levels after approximately 240 mm of rainfall. Our results
      provide evidence of order-of-magnitude concentration increases of a fallout
      radionuclide as a result of forest fire and rapid transport of radionuclides
      following fire that may have important implications for a wide range of
      geophysical, ecosystem, fire management, and risk-based issues.

PMID- 14674538
TI  - Long-term effects of nitrogen fertilizer use on ground water nitrate in two small
      watersheds.
AB  - Changes in agricultural management can minimize NO3-N leaching, but then the time
      needed to improve ground water quality is uncertain. A study was conducted in two
      first-order watersheds (30 and 34 ha) in Iowa's Loess Hills. Both were managed in
      continuous corn (Zea mays L.) from 1964 through 1995 with similar N fertilizer
      applications (average 178 kg ha(-1) yr(-1)), except one received applications
      averaging 446 kg N ha(-1) yr(-1) between 1969 and 1974. This study determined if
      NO3-N from these large applications could persist in ground water and baseflow,
      and affect comparison between new crop rotations implemented in 1996. Piezometer
      nests were installed and deep cores collected in 1996, then ground water levels
      and NO3-N concentrations were monitored. Tritium and stable isotopes (2H, 18O)
      were determined on 33 water samples in 2001. Baseflow from the heavily N
      fertilized watershed had larger average NO3-N concentrations, by 8 mg L(-1). Time
      of-travel calculations and tritium data showed ground water resides in these
      watersheds for decades. "Bomb-peak" precipitation (1963-1980) most influenced
      tritium concentrations near lower slope positions, while deep ground water was
      dominantly pre-1953 precipitation. Near the stream, greater recharge and mixed
      age ground water was suggested by stable isotope and tritium data, respectively.
      Using sediment-core data collected from the deep unsaturated zone between 1972
      and 1996, the increasing depth of a NO3-N pulse was related to cumulative
      baseflow (r2 = 0.98), suggesting slow downward movement of NO3-N since the first
      experiment. Management changes implemented in 1996 will take years to fully
      influence ground water NO3-N. Determining ground water quality responses to new
      agricultural practices may take decades in some watersheds.

PMID- 14674539
TI  - Effect of rainfall simulator and plot scale on overland flow and phosphorus
      transport.
AB  - Rainfall simulation experiments are widely used to study erosion and contaminant
      transport in overland flow. We investigated the use of two rainfall simulators
      designed to rain on 2-m-long (2-m2) and 10.7-m-long (32.6-m2) plots to estimate
      overland flow and phosphorus (P) transport in comparison with watershed-scale
      data. Simulated rainfall (75 mm h(-1)) generated more overland flow from 2-m-long
      (20 L m2) than from 10.7-m-long (10 L m2) plots established in grass, no-till
      corn (Zea mays L.), and recently tilled fields, because a relatively greater area
      of the smaller plots became saturated (>75% of area) during rainfall compared
      with large plots (<75% area). Although average concentrations of dissolved
      reactive phosphorus (DRP) in overland flow were greater from 2-m-long (0.50 mg L(
      1)) than 10.7-m-long (0.35 mg L(-1)) plots, the relationship between DRP and
      Mehlich-3 soil P (as defined by regression slope) was similar for both plots and
      for published watershed data (0.0022 for grassed, 0.0036 for no-till, and 0.0112
      for tilled sites). Conversely, sediment, particulate phosphorus (PP), and total
      phosphorus (TP) concentrations and selective transport of soil fines (<2 microm)
      were significantly lower from 2- than 10.7-m-long plots. However, slopes of the
      logarithmic regression between P enrichment ratio and sediment discharge were
      similar (0.281-0.301) for 2- and 10.7-m-long plots, and published watershed data.
      While concentrations and loads of P change with plot scales, processes governing
      DRP and PP transport in overland flow are consistent, supporting the limited use
      of small plots and rainfall simulators to assess the relationship between soil P
      and overland flow P as a function of soil type and management.

PMID- 14674540
TI  - Cotton defoliant runoff as a function of active ingredient and tillage.
AB  - Cotton (Gossypium hirsutum L.) defoliant runoff was recently identified as an
      ecological risk. However, assessments are not supported by field studies. Runoff
      potential of three defoliant active ingredients, dimethipin (2,3-dihydro-5,6
      dimethyl-1,4-dithiin 1,1,4,4-tetraoxide), thidiazuron (N-phenyl-N-1,2,3-thidiazol
      5-yl-urea), and tribufos (S,S,S-tributyl phosphorotrithioate) was investigated by
      rainfall simulation on strip (ST) and conventionally tilled (CT) cotton in south
      central Georgia. Simulated rainfall timing relative to defoliant application (1 h
      after) represented an extreme worst-case scenario; however, weather records
      indicate that it was not unrealistic for the region. Thidiazuron and tribufos
      losses were 12 to 15% of applied. Only 2 to 5% of the more water soluble
      dimethipin was lost. Although ST erosion rates were less, loss of tribufos, a
      strongly sorbing compound, was not affected. Higher sediment-water partition
      coefficients (kd) were measured in ST samples. This likely explains why no
      tillage related differences in loss rates were observed, but it is unknown
      whether this result can be generalized. The study was conducted in the first year
      following establishment of tillage treatments at the study site. As soil
      conditions stabilize, ST impacts may change. Data provide an estimate of the
      maximum amount of the defoliants that will run off during a single
      postapplication storm event. Use of these values in place of the default value in
      runoff simulation models used in pesticide risk assessments will likely improve
      risk estimate accuracy and enhance evaluation of comparative risk among these
      active ingredients.

PMID- 14674542
TI  - Size distribution of organic matter and associated propiconazole in agricultural
      runoff material.
AB  - Sorption and desorption characteristics of propiconazole (1-[[2-(2,4
      dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole) to
      different particle/aggregate-size fractions of agricultural runoff material were
      investigated. Emphasis was put on clay and colloidal size fractions to evaluate
      their role as potential sorbents and carriers for this pesticide. The runoff
      material was separated into size fractions ranging from 2 mm to ca. 15 nm by wet
      sieving, sedimentation, centrifugation, and membrane ultrafiltration. Each
      fraction was characterized by its organic C content and C/N ratio. Distinctive
      sorption properties of clay-sized particles and colloids were investigated. The
      obtained size fractions differed significantly in their organic C concentration,
      C/N ratio, and sorption properties to propiconazole. Organic matter was mainly
      associated in aggregates >2 microm. Binding of propiconazole to this coarse
      fraction made up 80% of the sorbed propiconazole. The distribution coefficient
      between solid and aqueous phases increased with decreasing particle size. The
      colloidal fraction (<0.16 microm) exhibited the highest sorbtivity, with a
      distribution coefficient of 113 L kg(-1), which was more than four times higher
      than that in the bulk sample (27 L kg(-1)). The fraction <2 microm represented 8%
      of the total sample weight, but contributed to 20% of the sorbed propiconazole.
      Strong hysteresis was observed for the sorption-desorption of propiconazole on
      the runoff material. Under dilution very little sorbed propiconazole will be
      released into the water phase. Due to its high sorbtivity and mobility and the
      strong sorption-desorption hysteresis, particles in the fraction <2 microm can be
      important carriers of propiconazole in runoff suspensions with high sediment
      load.

PMID- 14674541
TI  - Simulating pesticide leaching and runoff in rice paddies with the RICEWQ-VADOFT
      model.
AB  - There is a current need to simulate leaching and runoff of pesticide from rice
      (Oryza sativa L.) paddies for assessing environmental impacts on a valuable
      agricultural system. The objective of this study was to develop a model for
      determining predicted environmental concentration (PEC) in soil, runoff, and
      ground water through the linkage of two models, rice water quality model (RICEWQ)
      and vadose zone transport model (VADOFT), to simulate pesticide fate and
      transport within a rice paddy and underlying soil profile. Model performance was
      evaluated with a field data set obtained from a 2-yr field experiment in 1997 and
      1998 in northern Italy. The predictions of amount of pesticide running off from
      the paddy field and accumulating in the paddy sediment were in agreement with
      measured values. Leaching into the vadose zone accounted for approximately 19% of
      the applied dose, but only a small amount of chemical (<0.1%) was predicted to
      reach ground water at a 5-m depth due to sorption and transformation in the soil.
      The permeability of the soil and the water management practices in the paddy
      field were shown to have a strong influence on pesticide fate. These factors need
      to be well characterized in the field if model predictions are to be successful.
      The combined model developed in this work is an effective tool for exposure
      assessments for soil, surface water, and ground water, in the particular
      conditions of rice cultivation.

PMID- 14674543
TI  - Modeling of sorption and biodegradation of parathion and its metabolite paraoxon
      in soil.
AB  - To investigate the distribution of parathion [O,O-diethyl O-(4-nitrophenyl)
      phosphorothioate] and its highly toxic metabolite paraoxon [O,O-diethyl O-(4
      nitrophenyl)phosphate] between the soluble and sorbed pools in the soil, batch
      experiments were conducted to evaluate the rate of adsorption and desorption of
      14C-labeled parathion and paraoxon in soil. The mineralization and degradation of
      these products were also investigated during a 56-d experiment under controlled
      laboratory conditions. Adsorption patterns indicated initial fast adsorption
      reactions occurring within 4 h for both parathion and paraoxon. We also observed
      the formation of nonextractable residues. The paraoxon was more intensively
      degraded than the parathion, and production of p-nitrophenol and other
      metabolites was observed. A kinetic model was developed to describe the sorption
      and biodegradation rates of parathion, taking into account the production,
      retention, and biodegradation of paraoxon, the main metabolite of parathion.
      After fitting the parameters of the model we made a simulation of the kinetics of
      the appearance and disappearance of paraoxon. From the simulation we predicted a
      quantity of metabolite in the liquid phase amounting to 1% of the quantity of
      parathion initially applied. This is in agreement with the experimental data.

PMID- 14674544
TI  - Behavior of 14C-atrazine in Argentinean topsoils under different cropping
      managements.
AB  - Atrazine (6-chloro-N2-ethyl-N4-isopropyl-1,3,5-triazine-2,4-diamine) behavior was
      studied in four surface soils during incubations in laboratory conditions. Soils
      were chosen in relation to their cropping management (tillage and no tillage) and
      crop rotation system (continuous soybean [Glycine mar (L.) Merr.] and maize (Zea
      mays L.)-soybean rotation). A natural soil under brushwood was sampled as a
      reference. Atrazine use in field conditions was associated with maize cropping,
      thus only one soil received atrazine every other year. Atrazine behavior was
      characterized through the balance of 14C-U-ring atrazine radioactivity among the
      mineralized fraction, the extractable fraction, and the nonextractable bound
      residues. Soil organic matter capacity to form bound residues was characterized
      using soil size fractionation. Accelerated atrazine mineralization was only
      observed in the soil receiving atrazine in field conditions. Atrazine application
      every other year was enough to develop a microflora adapted to triazine ring
      mineralization. Bound residue formation was rapid and increased with soil organic
      matter content. The coarsest soil size fractions (2000-200 and 200-50 microm)
      containing the nonhumified organic matter presented the highest capacity to form
      bound residues. No effect of tillage system was observed, probably because of the
      uniform sampling depth at 20 cm, hiding the stratification pattern of soil
      organic matter in non-tilled soils.

PMID- 14674545
TI  - Effect of formulation on the behavior of 1,3-dichloropropene in soil.
AB  - The fumigant 1,3-dichloropropene (1,3-D) has been identified as a partial
      replacement for methyl bromide (CH3Br) in soil fumigation. 1,3-Dichloropropene is
      formulated for soil fumigation as Telone II (Dow AgroSciences, Indianapolis, IN)
      for shank application and as an emulsifiable concentrate (EC) (Telone EC or
      InLine; Dow AgroSciences) for drip application. This study investigated the
      effect of formulation on the phase partitioning, transformation rate, and
      volatilization of 1,3-D isomers. Air-water partitioning coefficients (K(H)) were
      slightly higher for Telone II than for Telone EC, presumably due to the higher
      apparent water solubility of the EC formulation. Sorption of 1,3-D isomers in two
      soils was not affected by formulation. Formulation had no significant effect on
      the rate of 1,3-D transformation in water or soil. In general, differences in the
      rate of 1,3-D transformation and phase partitioning due to formulation as Telone
      II or Telone EC were very small. Thus, the effect of formulation on 1,3-D fate
      may be ignored in transformation and phase partition of 1,3-D in water and soil.
      Packed soil columns without plastic tarp indicated that with relatively shallow
      subsurface (10 cm) drip application of Telone EC, emission of 1,3-D isomers was
      more rapid and produced greater maximum instantaneous flux than deeper (30 cm)
      shank injection of Telone II. Both application methods resulted in the same
      cumulative emissions for both isomers, 45% for (E)-1,3-D and approximately 50%
      for (Z)-1,3-D. These results suggest that for drip application of fumigants to be
      effective in reducing emissions, the fumigant must be applied at sufficient
      depths to prevent rapid volatilization from the soil surface if the water
      application rate does not sufficiently restrict vapor diffusion.

PMID- 14674546
TI  - Biogeochemistry of fluoride in a plant-solution system.
AB  - Fluoride (F-) pollutants can harm plants and the animals feeding on them.
      However, it is largely unknown how complexing and chelating agents affect F
      bioavailability. Two studies were conducted that measured F- bioavailability and
      uptake by rice (Oryza sativa L.). In the first study, rice was grown in solution
      culture (pH 5.0) with 0, 2, or 4 mM F- as KF to compare the interaction of F-
      with humic acid (HA) and with a conventional chelating agent, N
      hydroxyethylenthylenediaminetriacetic acid (HEDTA). In the second study, F was
      supplied at 0, 0.5, 1.0, and 2.0 mM KF with an additional 2 mM F- treatment
      containing solution Ca at 2x (2 mM Ca) the level used in the first study, to test
      the effect added Ca had on F- availability and uptake. Total biomass was greatest
      with HEDTA and F- < 1 mM. Leaf and stem F concentrations increased exponentially
      as solution F- increased linearly, with nearly no F partitioning into the seed.
      Results suggest that F was taken up as HF0 while F- uptake was likely restricted.
      Additionally, F- competed with HA for Ca, thus preventing the formation of Ca-HA
      flocculents. The addition of soluble Ca resulted in the precipitation of CaF2
      solids on the root surface, as determined by tissue analysis and energy
      dispersive X-ray spectroscopy.

PMID- 14674547
TI  - Contrasting physiological responses of dwarf sea-lavender and marguerite to
      simulated sea aerosol deposition.
AB  - Plants of two wild native species from littoral areas, marguerite [Argyranthemum
      coronopifolium (Willd.) C.J. Humphries] and dwarf sea-lavender [Limonium
      pectinatum (Aiton) O. Kuntze], grown in an unheated plastic greenhouse, were
      sprayed 2 to 3 min per day over a 7-d period with different aqueous solutions
      containing (i) an anionic surfactant (S1); (ii) a solution simulating the
      composition of sea aerosol (S2); (iii) a solution simulating sea aerosol with
      anionic surfactant (S3), and (iv) deionized water alone (control). The plant
      resistance to sea aerosol and the ability to recover from treatments were
      studied. By the end of the spraying period, marguerite showed a significant
      reduction in growth compared with control. However, most of the growth parameters
      were significantly unaffected in dwarf sea-lavender when plants were treated with
      sea aerosol containing surfactant. Measurements of water relations variables in
      marguerite showed a slight decrease in leaf turgor potential after spraying with
      sea aerosol containing surfactant. The surfactant enhanced the foliar absorption
      of salt in marguerite plants, inducing reductions in leaf stomatal conductance
      and causing such damage in the photosynthetic apparatus that the level of net
      photosynthesis decreased and had not recovered by the end of the experiment. The
      treatments had no effect on leaf stomatal conductance and photosynthesis rate in
      dwarf sea-lavender plants. The response of the species studied to sea aerosol was
      related to the degree of salinity tolerance. Although both species are wild
      native plants from littoral areas, marguerite is not salt tolerant and was the
      most sensitive to the sea aerosol treatments, while dwarf sea-lavender, a
      halophyte species, was more efficient at decreasing the toxic salt content of the
      tissues as its growth and ornamental characteristics were not affected.

PMID- 14674548
TI  - Barley, a potential species for initial reclamation of saline composite tailings
      of oil sands.
AB  - The oil sands industry in Alberta (Canada) has developed the composite tailings
      (CT) process to reduce the fluid fine tails resulting from the processing of oil
      sands. This process uses a chemical coagulant (gypsum or alum) to produce
      aggregated fines (clay), so they are retained with the coarse sand fraction of
      the extraction tailings to form CT, from which fines-free water is released
      relatively quickly compared with untreated tailings. The resulting CT and CT
      waters are saline-sodic, with Na+, SO4(2-), and Cl- being the dominant ions. When
      freshly deposited, the CT deposits are too soft for access by reclamation
      equipment, and the time required for these deposits to remove the water
      sufficiently to support traffic is uncertain. A greenhouse study was designed to
      determine the suitability of barley (Hordeum vulgare L.) for reclamation of fresh
      CT deposits and to evaluate benefits of peat amendments. This study assessed
      germination, early plant growth, chlorophyll content, and survival of barley
      growing in alum- and gypsum-treated CT, with and without peat amendment. Ion and
      trace metal accumulation in the root and shoot tissues of barley was determined.
      Amendment of CT with peat improved germination, survival, and growth of barley,
      but did not prevent leaf injury (probably due to Na and Cl- and possibly multiple
      nutrient deficiency). Field studies will be undertaken to validate our greenhouse
      results suggesting that barley could be used to improve dewatering of the freshly
      deposited substrates, reduce soil erosion, and facilitate leaching of ions by
      root penetration into the substrate.

PMID- 14674549
TI  - Cesium-134 and strontium-85 in strawberry plants following wet aerial deposition.
AB  - The understanding of the processes that control the behavior of radionuclides in
      crops can support policymakers to take actions to protect the environment and
      safeguard human health. Data concerning the behavior of radionuclides in fruits
      are limited. Strawberry (Fragaria x ananassa Duchesne) plants were contaminated
      on the aboveground part by sprinkling an aqueous solution of 134Cs and 85Sr at
      three growing stages: predormancy, anthesis, and beginning of ripening.
      Intercepted activity was more affected by the posture and physical orientation of
      leaves rather than by leaf area or biomass. Fruit interception ranges from 0.2 to
      1.2% of the sprinkled activity. Translocation coefficients from leaf to fruit are
      on the order of 10(-4) for 134Cs and 10(-5) for 85Sr. Translocation reaches its
      highest intensity between anthesis and ripening. If deposition occurs when plants
      are bearing fruits, the fruit activity will be affected by the activity initially
      deposited on the fruit surfaces. This is important for 85Sr as it is not
      translocated in the phloem. The loss of the dead leaves at the resumption of
      growth causes high plant decontamination, but a fraction of both radionuclides
      remains in the storage organs, roots, and shoots, which is retranslocated to
      fruits in the following spring. The values of the environmental half-time, t(w),
      after deposition at predormancy are 114 d for 134Cs and 109 d for 85Sr. Cesium
      134 tends to be allocated to fruits, while 85Sr remains in leaves and crowns.
      Translocation of radionuclides to roots results in soil contamination.

PMID- 14674550
TI  - Phenols and flavonoids in Aleppo pine needles as bioindicators of air pollution.
AB  - The aim of the present study is to assess whether certain ecophysiological
      responses (contents of total phenols, total proanthocyanidins, and total and
      simple flavonols), in the needles of Aleppo pines (Pinus halepensis Mill.) may be
      valid bioindicators for the assessment of the air quality. Samples were taken at
      five natural sites polluted by various pollutants (NO, NO2, other NOx, SO2, and
      O3). The results show a decrease in total phenol concentrations with levels of
      nitrogen oxide pollutions (significant negative correlations between the total
      phenol concentrations and concentrations of NO, NO2, and other NOx). Total
      flavonoids (total flavonols and proanthocyanidins) are useful bioindicators for
      ozone pollution (significant negative correlations between total
      proanthocyanidins and the concentrations of ozone and significant positive
      correlations between total flavonols and the ozone pollution). Sulfur dioxide
      pollution is distinguished by low concentrations in quercetin, isorhamnetin, and
      kaempferol (significant negative correlations between these simple flavonols and
      the concentrations of SO2). This work confirms the strong interest of using the
      phenolic compounds of Pinus halepensis as biological indicators of air quality.

PMID- 14674551
TI  - Uptake and release of cesium-137 by five plant species as influenced by soil
      amendments in field experiments.
AB  - Phytoextraction field experiments were conducted on soil contaminated with 0.39
      to 8.7 Bq/g of 137Cs to determine the capacity of five plant species to
      accumulate 137Cs and the effects of three soil treatments on uptake. The plants
      tested were redroot pigweed (Amaranthus retroflexus L. var. aureus); a mixture of
      redroot pigweed and spreading pigweed (A. graecizans L.); purple amaranth (A.
      cruteus L.) x Powell's amaranth (A. powellii S. Watson), referred to here as the
      amaranth hybrid; Indian mustard [Brassica juncea (L.) Czern.]; and cabbage
      (Brassica oleracea L. var. capitata). For control plants, the concentration
      ratios (CR) of 137Cs were greatest for redroot pigweed and the amaranth hybrid,
      with average CR values of 1.0 +/- 0.24 and 0.95 +/- 0.14, respectively. The
      lowest value was for Indian mustard at 0.36 +/- 0.10. The soil treatments
      included (i) application of NH4NO3 solution to the soil after plants had matured,
      (ii) addition of composted manure to increase organic matter content of the soil,
      (iii) combination of the manure and ammonium solution treatments, and (iv)
      controls. The ammonium solution gave little overall increase in accumulation of
      137Cs. The use of composted manure also had little influence, but the combination
      of the composted manure with application of ammonium solutions had a distinctly
      negative effect on plant uptake of 137Cs. On average the fraction of 137Cs taken
      up from the soil was reduced by 57.4 +/- 1.2% compared with controls. This was
      the result of release of competing ions, primarily Ca, from the manure and was
      observed across all five plant species tested. The application of ammonium
      solution took place in the last two weeks before harvest. The reduction of plant
      137Cs content, by addition of the ammonium solution, as it interacted with the
      manure, indicates that substantial quantities 137Cs can be released from the
      shoots of plants as a result of sudden changes in soil solution chemistry.

PMID- 14674552
TI  - Revisiting nitrate concentrations in the Des Moines River: 1945 and 1976-2001.
AB  - Recent compilations of historical and contemporary riverine nitrate (NO3)
      concentrations indicate that concentrations in many rivers in the north-central
      USA increased during the second half of the 20th century. The Des Moines River
      near Des Moines, Iowa, however, was reported to have had similar NO3
      concentrations in 1945 and the 1980s, in spite of substantially greater N input
      to the watershed during the latter period. The objective of this study was to
      reconsider the comparison of historical and contemporary NO3 concentrations in
      the Des Moines River near Des Moines in light of the following: (i) possible
      errors in the historical data used, (ii) variations in methods of sample
      collection, (iii) variations in location of sampling, and (iv) additional data
      collected since 1990. We discovered that an earlier study had compared the flow
      weighted average concentration in 1945 to arithmetic annual average
      concentrations in the 1980s. The intertemporal comparison also appeared to be
      influenced by differences in sample collection methods and locations used at
      different times. Depending on the model used and the estimated effects of
      composite sample collection, the 1945 arithmetic average NO3 concentration was
      between 44 and 57% of the expected mean value at a similar water yield during
      1976-2001. The flow-weighted average NO3 concentration for 1945 was between 54
      and 73% of the expected mean value at a similar water yield during 1976-2001. The
      difference between NO3 concentrations in 1945 and the contemporary period are
      larger than previously reported for the Des Moines River.

PMID- 14674553
TI  - Modeling surface water critical loads with PROFILE: possibilities and challenges.
AB  - The critical load concept has become a valuable tool for policymakers in the
      European negotiations on emission reductions. Despite the international
      acceptance, ongoing validation of critical load methodology is of the utmost
      importance to avoid a situation where the calculation results are difficult to
      defend. In this paper we explore the potential of using the steady state soil
      chemistry model PROFILE as an alternative to the Steady State Water Chemistry
      (SSWC) method for calculating critical loads of acidity. The hypothesis is that
      the uncertainty in prediction of preindustrial leaching of base cations is
      reduced when soil properties instead of lake chemistry are used as input data.
      Paleolimnological reconstructions of preindustrial lake chemistry are used to
      test PROFILE. As PROFILE requires soil data that are not generally available on a
      catchment level, we used distributions of crucial parameters from soil survey
      data within the vicinity of five lakes for which paleoecological pH
      reconstructions were available. An important concern is the characterization of
      catchment hydrology. A calibration of the "effective" soil depth, needed to give
      PROFILE predictions that coincided with paleolimnology, suggested that
      approximately 0.6 m of the total soil depth was hydrologically active in
      supplying acid neutralizing capacity (ANC) to runoff through weathering. At
      present, there is insufficient evidence to either recommend or reject the PROFILE
      model for surface water critical loads. Before such a judgement can be made, the
      approach presented here has to be tested for other regions, and the definition of
      catchment hydrology needs to be investigated further.

PMID- 14674554
TI  - Intra-storm study of solute chemical composition of overland flow water in two
      agricultural fields.
AB  - Few studies have assessed the transport of dissolved nutrients at the field scale
      under natural rainfall conditions. Hysteresis between dissolved nutrients and
      discharge behavior can complicate such assessments and this effect has only been
      examined qualitatively. In this study, we investigated factors contributing to
      short-term variations of dissolved cation (Ca, Mg, Na, and K) and anion (soluble
      reactive phosphorus [SRP], NO3, and SO4) concentrations in runoff water and
      developed a quantitative method to study their hysteretic behavior. Within-storm
      variations of dissolved nutrient concentrations were determined in two
      agricultural fields during four natural rainfall events along with discharge,
      sediment, antecedent soil water conditions, and nutrient contents. For each
      event, nutrient loads were plotted against discharge during the rising and
      falling limb of the runoff hydrograph. The resulting hysteresis curves were
      characterized by an index H, which is the ratio between the integrated areas
      under the rising and falling curves of the hydrograph. Results showed that
      nutrient concentrations increased with time during each event. Counterclockwise
      (H < 1) hysteresis, occurring when the falling limb had larger loads, was found
      when soils were initially dry whereas clockwise hysteresis (H > 1) was associated
      with prior wet soil conditions. Two hypotheses are suggested to explain these
      variations. First, suspended sediments could have acted as a sink for dissolved
      nutrients and the sensitivity of nutrients to hydrological conditions was
      determined by their preferential sorption on these sediments. Second, movement of
      nutrients into runoff occurred more readily as soils became wetter during an
      event.

PMID- 14674555
TI  - Targeted sampling protocol as prelude to bacterial source tracking with
      Enterococcus faecalis.
AB  - Recent studies suggest that host origin databases for bacterial source tracking
      (BST) must contain a large number of isolates because bacterial subspecies change
      with geography and time. A new targeted sampling protocol was developed as a
      prelude to BST to minimize these changes. The research was conducted on the
      Sapelo River, a tidal river on the Georgia coast. A general sampling of the river
      showed fecal enterococcal numbers ranging from <10 (below the limit of detection)
      to 990 colony-forming units (CFU) per 100 mL. Locations with high enterococcal
      numbers were combined with local knowledge to determine targeted sampling sites.
      Fecal enterococcal numbers around one site ranged from <10 to 24,000 CFU per 100
      mL. Bacterial source tracking was conducted to determine if a wastewater
      treatment facility at the site was responsible for this contamination. The fecal
      indicator bacterium was Enterococcus faecalis. Ribotyping, automated with a
      RiboPrinter (DuPont Qualicon, Wilmington, DE), was the BST method. Thirty-seven
      ribotypes were observed among 83 Ent. faecalis isolates obtained from the Sapelo
      River and the wastewater lagoon. Sixteen ribotypes were associated with either
      the river or the lagoon, and only five ribotypes (14%) were shared. Nevertheless,
      these five ribotypes represented 39 of the 83 Ent. faecalis isolates, almost a
      majority (47%). These results suggest that the fecal contamination in the river
      came from the wastewater treatment facility. As a prelude to BST, targeted
      sampling minimized subspecies changes with geography and time, and eliminated the
      need for a permanent host origin database by restricting BST to a small
      geographic area and requiring sampling to be completed in one day.

PMID- 14674556
TI  - Infiltration and adsorption of dissolved atrazine and atrazine metabolites in
      buffalograss filter strips.
AB  - Vegetated filter strips (VFS) potentially reduce the off-site movement of
      herbicides from adjacent agricultural fields by increasing herbicide mass
      infiltrated (Minf) and mass adsorbed (Mas) compared with bare field soil.
      However, there are conflicting reports in the literature concerning the
      contribution of Mas to the VFS herbicide trapping efficiency (TE). Moreover, no
      study has evaluated TE among atrazine (6-chloro-N-ethyl-N'-isopropyl
      [1,3,5]triazine-2,4-diamine) and atrazine metabolites. This study was conducted
      to compare TE, Minf, and Mas among atrazine, diaminoatrazine (DA, 6
      chloro[1,3,5]triazine-2,4-diamine), deisopropylatrazine (DIA, 6-chloro-N-ethyl
      [1,3,5]triazine-2,4-diamine), desethylatrazine (DEA, 6-chloro-N-isopropyl
      [1,3,5]triazine-2,4-diamine), and hydroxyatrazine (HA, 6-hydroxy-N-ethyl-N'
      isopropyl-[1,3,5]triazine-2,4-diamine) in a buffalograss VFS. Runoff was applied
      as a point source upslope of a 1- x 3-m microwatershed plot at a rate of 750 L h(
      1). The point source was fortified at 0.1 microg mL(-1) atrazine, DA, DIA, DEA,
      and HA. After crossing the length of the plot, water samples were collected at 5
      min intervals. Water samples were extracted by solid phase extraction and
      analyzed by high performance liquid chromatography (HPLC) photodiode array
      detection. During the 60-min simulation, TE was significantly greater for
      atrazine (22.2%) compared with atrazine metabolites (19.0%). Approximately 67 and
      33% of the TE was attributed to Minf and Mas, respectively. These results
      demonstrate that herbicide adsorption to the VFS grass, grass thatch, and/or soil
      surface is an important retention mechanism, especially under saturated
      conditions. Values for Mas were significantly higher for atrazine compared with
      atrazine's metabolites. The Mas data indicate that atrazine was preferentially
      retained by the VFS grass, grass thatch, and/or soil surface compared with
      atrazine's metabolites.

PMID- 14674557
TI  - Solute movement through an allophanic soil.
AB  - Allophanic soils are widespread around the world, but little research has been
      done on their transport properties. This study reveals the effect of two soil
      water potential heads and two water-flow regimes of continuous and intermittent
      flow on solute transport through undisturbed soil columns of Horotiu silt loam
      (Typic Hapludand), an allophanic soil. Two different methods--breakthrough curves
      (BTCs) and time domain reflectometry (TDR)--were employed to determine the extent
      of preferential solute transport in the topsoil. The TDR data were also used to
      look at the depth dependence of the transport properties. The convection
      dispersion equation (CDE) with the appropriate boundary conditions adequately
      described the movement of both Br and Cl under the various flow conditions.
      Although no preferential flow was found under the imposed unsaturated flow
      conditions, the flow of water and transport of solute became more uniform with
      depth. The results show that both Br and Cl are retarded in this allophanic soil.
      Retardation values range from 1.5 to 1.9, and, as the TDR data showed, increase
      from the depth of 5.0 to 10.0 cm. Intermittent leaching results showed that there
      was no effect on solute concentrations in the leachate following no-flow periods.
      This suggests that water and solute transport in this soil were either relatively
      uniform or that transverse mixing during flow was already fast enough to
      eliminate concentration gradients between regions of different "mobility."

PMID- 14674558
TI  - Halting the upward trend in soluble phosphorus transported from a grassland
      catchment.
AB  - An upward trend in soluble reactive phosphorus (SRP) concentrations in Northern
      Ireland rivers leading to increased eutrophication has been reported for the last
      two decades. To identify if a similar trend could be observed in land drainage
      waters SRP and other P fractions were measured weekly from 1989 to 1997 in land
      drainage from a 9-ha grassland catchment in Northern Ireland that had a mean P
      surplus applied of 23.4 kg P ha(-1) yr(-1). Regressions of annual median
      concentrations of P fractions in land drainage waters against time for 1989
      through to 1997 showed significant increases of SRP and soluble unreactive
      phosphorus (SUP) of 2.4 and 1.2 microg P L(-1) yr(-1), respectively. However, the
      annual flow-weighted concentrations and loads of all P fractions did not show
      significant increases with time. During the period 1998-2000 a change of
      management was introduced when only maintenance dressings of P were applied to
      the catchment according to Ministry of Agriculture, Fisheries and Food
      guidelines. This resulted in significant reductions in SRP concentrations in 2000
      compared with 1997.

PMID- 14674559
TI  - Modeling macropore flow effects on pesticide leaching: inverse parameter
      estimation using microlysimeters.
AB  - Macropore flow is a key factor determining pesticide fate, but models accounting
      for this process need parameters that cannot be easily measured. This study was
      conducted to investigate the use of inverse techniques to estimate parameters
      controlling macropore flow and pesticide fate in the dual-permeability model
      MACRO. Undisturbed columns were sampled at three landscape positions (hilltop,
      slope, hollow) with contrasting texture and organic carbon content. Transient
      leaching experiments were performed for an anionic tracer and the herbicide MCPA
      (4-chloro-2methylphenoxy acetic acid) during a 4-mo period, first under natural
      rainfall, and then under controlled irrigation in the laboratory. The tracer
      breakthrough for the liner-textured soil from the hilltop showed strong evidence
      of macropore flow, resulting in a rapid leaching of MCPA, while leaching was
      minimal from the organic-rich hollow soil, since macropore flow was weaker and
      adsorption stronger. The MACRO model was linked to the inverse modeling program
      SUFI (Sequential Uncertainty Fitting) to enable calibration of nine key model
      parameters. Based on calculated model efficiencies, MACRO-SUFI gave generally
      good predictions of water movement and tracer and pesticide transport, although
      some errors were attributed to difficulties in simulating the effects of soil
      moisture on degradation and the timing of water outflows. Even after calibration,
      significant uncertainties remained for some key parameters controlling macropore
      flow. Nevertheless, the parameter estimates were significantly different between
      landscape positions and could also be related to basic soil properties. The
      posterior uncertainty ranges could probably be reduced with a more exhaustive
      sampling of the parameter space and improved experimental designs.

PMID- 14674560
TI  - Aluminum effect on dissolution and precipitation under hyperalkaline conditions:
      I. Liquid phase transformations.
AB  - Substantial amounts of self-boiling, Al-rich, hyperalkaline, and saline high
      level waste fluids (HLWF) were deposited to the vadose zone at the Hanford Site,
      in Washington State. The objective of this study was to investigate the effects
      of similar fluids on the extent of dissolution and precipitation in the
      sediments. Metal- and glass-free systems were used to conduct batch experiments
      at 323 K under CO2 and O2 free conditions. Base-induced dissolution of the soil
      minerals was rapid in the first 48 h as indicated by immediate releases of Si and
      Fe into the soil solution. Potassium release lagged behind and dissolution of K
      bearing minerals (mica and K-feldspar) proceeded faster only after 2 to 3 d of
      the experiment. Silicon and Fe release exhibited high dependence on aqueous [Al]
      (rate orders <-1), because Al decreased free OH concentration in the contact
      solution and probably inhibited soil mineral dissolution. Initial K release
      exhibited low dependence on [Al] (fractional rate orders). Initial dissolution
      rates calculated based on Si release varied with aqueous [Al] from 29.47 to 4.35
      x 10(-12) mol m(-2) s(-1). Aluminum participated in the formation of the
      secondary phases (precipitation rates of 10(-8) mol s(-1)) but the overall
      precipitation rate of alumino-silicate secondary phases was probably controlled
      by aqueous [Si] (rates of 10(-9), and rate constants between 0.0054 and 0.0084 h(
      1)). The changes in the soil solution chemistry (release of K, Si, Fe, and other
      elements) may play a significant role in the fate of radionuclides and
      contaminants like Cs, Sr, Cr, and U in the Hanford sediments.

PMID- 14674561
TI  - Aluminum effect on dissolution and precipitation under hyperalkaline conditions:
      II. Solid phase transformations.
AB  - The high-level radioactive, Al-rich, concentrated alkaline and saline waste
      fluids stored in underground tanks have accidentally leaked into the vadose zone
      at the Hanford Site in Washington State. In addition to dissolution,
      precipitation is likely to occur when these waste fluids contact the sediments.
      The objective of this study was to investigate the solid phase transformations
      caused by dissolution and precipitation in the sediments treated with solutions
      similar to the waste fluids. Batch experiments at 323 K were conducted in metal-
      and glass-free systems under CO2 and O2 free conditions. Results from X-ray
      diffraction (XRD), quantitative X-ray diffraction (QXRD), scanning electron
      microscopy (SEM), energy dispersive spectroscopy (EDS), and energy dispersive X
      ray fluorescence spectroscopy (EDXRF) indicated that significant solid phase
      transformations occurred in the sediments contacted with Al-rich, hyperalkaline,
      and saline solutions. The XRD and QXRD analyses confirmed that smectite and most
      likely biotite underwent dissolution. The SEM and the qualitative EDS analyses
      confirmed the formation of alumino-silicates in the groups of cancrinite and
      probably sodalite. The morphology of the alumino-silicates secondary phases
      changed in response to changes in the Si/Al aqueous molar ratio. The
      transformations in the sediments triggered by dissolution (weathering of soil
      minerals) and precipitation (formation of secondary phases with high specific
      surface area and probably high sorption capacities) may play a significant role
      in the immobilization and ultimate fate of radionuclides and contaminants such as
      Cs, Sr, and U in the Hanford vadose zone.

PMID- 14674562
TI  - Effect of peroxide on neutralization-potential values of siderite and other
      carbonate minerals.
AB  - To assess quantitatively the effect of peroxide addition to standard static tests
      of the neutralization potential (NP) of mine wastes, 10 specimens of carbonate
      minerals, including five of siderite (FeCO3) and two of rhodochrosite (MnCO3),
      were analyzed by electron microprobe. The compositions of the siderite span a
      range from 60 to 86 mol % Fe. Tests of NP for the siderite diluted with 80% (w/w)
      kaolinite gave values of 647 to 737 kg CaCO3 equivalent per Mg for determinations
      by the standard Sobek method. However, if it is assumed that the ferrous
      carbonate component of the mineral does not contribute to NP in field situations
      because oxidation of Fe(II) to Fe(III) and the subsequent hydrolysis of Fe(III)
      leads to the release of an equivalent amount of acid, then the calculated NP for
      the samples ranges from 110 to 390 kg CaCO3 equivalent per Mg. Two different
      methods involving the addition of peroxide to the test solutions were successful
      in bringing the measured NP values closer to the theoretical ones. By contrast,
      the tests with rhodochrosite indicated the Mn(II) to be stable. For long-term
      environmental planning, especially for wastes from metalliferous sulfide-poor
      deposits in which gradual dissolution of silicate and aluminosilicate minerals
      may be involved in attenuating the acidity, consideration in the overall NP
      budget needs to be given to the ferrous iron content of those minerals. The
      presence of Fe2+-bearing minerals, especially carbonates, in tested mine-waste
      materials may lead to overestimated Sobek NP values, thus increasing the risk of
      poor-quality drainage and the need for costly remediation.

PMID- 14674563
TI  - An integrated chemical, thermal, and microbiological approach to compost
      stability evaluation.
AB  - The evaluation of compost stability is of the utmost importance for the
      reliability of composting as a recycling strategy. To date there is no single
      parameter that can give a sure indication of the stability of composts from
      different starting materials. This paper investigates different methods of
      evaluating the dynamics of transformation of materials and the stability level of
      the end products in a composting process. The following parameters were
      determined on compost samples of different ages from cotton (Gossypium herbaceum
      L.) cardings and yard wastes: humification index (HI), degree of humification
      (DH), thermogravimetry (TG) microbial biomass C (B(C)), and ninhydrin-reactive N
      (B(NIN)). Finally, from TG, derivative thermogravimetry (DTG) and differential
      scanning calorimetry (DSC) thermal stability parameters were deduced.
      Humification parameters in the end products (0.2 and 81% for HI and DH,
      respectively) showed the effective stability reached by the organic matter (OM).
      Thermal analysis evidenced the presence of two main organic pools with different
      thermal stability. During composting a relative increase in the more stable
      organic pool was indicated by the variation of the thermostability index R1 from
      0.41 to 0.74. The parameter R1 was significantly correlated with both HI (r = 
      0.94; P < 0.05) and DH (r = 0.97; P < 0.05). Microbial biomass content dynamics
      reflected the availability of readily decomposable substrates. The ratio between
      B(NIN) and total N in the end product was 0.96%, indicating a good stability
      level. The simultaneous application of different approaches, considering
      different properties of composting materials, provides a more complete
      description of the stability and quality reached by the organic materials.

PMID- 14674564
TI  - Sorption of arsenic from soil-washing leachate by surfactant-modified zeolite.
AB  - Post-treatment of leachate from soil-washing remedial actions may be necessary
      depending on the amounts of dissolved contaminants present. Uptake of arsenic
      species by surfactant-modified zeolite (SMZ) from a synthetic soil leachate (pH
      of approximately 12 [NaOH]) was measured as a test of SMZ as a post-treatment
      sorbent. Batch sorption isotherms were prepared using leachate to SMZ ratios from
      40:1 to 4:1, and temperatures of 25 and 15 degrees C. Equilibrium levels of
      dissolved and total solution arsenic were similar. At each temperature, sorption
      appeared to reach a plateau or maximum, then decreased at the highest solution
      concentration, corresponding to the lowest amount of zeolite added (2.5 g). A
      maximum sorption value of 72.0 mmol of arsenic per kg of SMZ (5400 mg/kg) was
      observed at 25 degrees C, and 42.1 mmol/kg (3150 mg/kg) at 15 degrees C. Total
      arsenic recoveries varied from 74 to 125%. Surfactant-modified zeolite removed up
      to 97% of dissolved organic carbon and decolorized the leachate solutions.
      Excluding the points for the highest arsenic to SMZ ratio, the sorption isotherms
      were well described by the linearized form of the Langmuir equation, with
      coefficients of determination greater than 0.90 at both temperatures. Sorption of
      arsenic by SMZ is attributed to anion exchange with counterions on the surfactant
      head groups, and/or partitioning of organic carbon-complexed arsenic into the
      surfactant bilayer.

PMID- 14674565
TI  - Water-quality effects of incorporating poultry litter into perennial grassland
      soils.
AB  - Poultry litter provides a rich source of nutrients for perennial forages, but the
      usual practice of surface-applying litter to pastures can degrade water quality
      by allowing nutrients to be transported from fields in surface runoff, while much
      of the NH4-N volatilizes. Incorporating litter into the soil can minimize such
      problems in tilled systems, but has not been used for perennial forage systems.
      In this study, we minimized disturbance of the crop, thatch, and soil structure
      by using a knifing technique to move litter into the root zone. Our objective was
      to determine effects of poultry litter incorporation on quantity and quality of
      runoff water. Field plots were constructed on a silt loam soil with well
      established bermudagrass [Cynodon dactylon (L.) Pers.] and mixed grass forage.
      Each plot had 8 to 10% slopes, borders to isolate runoff, and a downslope trough
      with sampling pit. Poultry litter was applied (5.6 Mg ha(-1)) by one of three
      methods: surface-applied, incorporated, or surface-applied on soil-aeration cuts.
      There were six treatment replications and three controls (no litter). Nutrient
      concentrations and mass losses in runoff from incorporated litter were
      significantly lower (generally 80-95% less) than in runoff from surface-applied
      litter. By the second year of treatment, litter-incorporated soils had greater
      rain infiltration rates, water-holding capacities, and sediment retention than
      soils receiving surface-applied litter. Litter incorporation also showed a strong
      tendency to increase forage yield.

PMID- 14674566
TI  - Redistribution of slurry components as influenced by injection method, soil, and
      slurry properties.
AB  - The distribution of moisture, degradable C, and N after direct injection of
      slurry can affect the turnover and plant availability of slurry N. This study
      examined effects of injection method, soil conditions, and slurry properties on
      the infiltration of several slurry components under practical conditions. The
      water retention capacity of 22 pig and cattle slurries was quantified by dialysis
      at -0.016, -0.047, and -0.100 MPa. All slurries followed the relationship:
      relative water loss = 1/(1 + aVS[volatile solids]), indicating that retention of
      liquids in the slurry injection zone can be predicted from slurry VS and soil
      water potential. Two-disc injection and harrow tine injection were simulated (no
      slurry applied) in five trials. Two trials indicated that disc injection resulted
      in higher permeability compared with harrow tine injection. In a separate
      experiment, soil moisture and dissolved ions were monitored in and around
      injection slits amended with pig or cattle slurry. Moisture gradients, which were
      recorded with small printed-circuit-board (PCB) time-domain-reflectometry (TDR)
      probes, were temporally stable and reestablished following rainfall. Slit
      sections with pig and cattle slurry containing 13C-acetate and 15N-ammonium
      showed a shift in the 13C to 15N ratio of the injection zone within 24 h, which
      was explained by removal of dissolved C and/or retention of NH4+. Cattle slurry
      was more concentrated around the injection slit than pig slurry, and greater
      contact between slurry and soil was obtained with harrow tine injection. The
      heterogeneity of slurry C and N distribution after direct injection should be
      accounted for in models describing slurry N turnover.

PMID- 14674567
TI  - Use of alkaline extraction to quantify sulfate concentration in oxidized mine
      tailings.
AB  - An alkaline extraction method has been developed for the determination of total
      sulfate in mine tailings containing secondary sulfate minerals formed by the
      oxidation of primary sulfides. Oxidized tailings were extracted with a 0.3 M NaOH
      solution at a liquid/solid ratio of 30 at room temperature for 16 h. The sulfate
      concentration in the extracts was determined by ion chromatography (IC). The
      coefficient of variation for sulfate determinations ranged from 1.9 to 3.2% for
      five tailings samples collected at two tailings impoundments. Mineralogical
      analysis of the tailings by scanning electron microscopy/X-ray energy dispersive
      spectrometry (SEM/EDS) demonstrated that the extraction of sulfate was complete,
      with the exception of extremely insoluble barite. The proposed method is simple,
      yields an accurate yet rapid measurement of sulfate, and involves a safer
      laboratory operation than conventional methods that make use of strong HCl acid
      solutions. Moreover, this method allows the specific measurement of sulfate in
      the extract, whereas conventional methods are generally limited to the
      measurement of total S by inductively coupled plasma atomic emission spectrometry
      (ICP-AES) due to the interference of chloride with sulfate in IC.

PMID- 14674568
TI  - Potential nitrification and denitrification on different surfaces in a
      constructed treatment wetland.
AB  - Improved understanding of the importance of different surfaces in supporting
      attached nitrifying and denitrifying bacteria is essential if we are to optimize
      the N removal capacity of treatment wetlands. The aim of this study was therefore
      to examine the nitrifying and denitrifying capacity of different surfaces in a
      constructed treatment wetland and to assess the relative importance of these
      surfaces for overall N removal in the wetland. Intact sediment cores, old pine
      and spruce twigs, shoots of Eurasian watermilfoil (Myriophyllum spicatum L.), and
      filamentous macro-algae were collected in July and November 1999 in two basins of
      the wetland system. One of the basins had been constructed on land that contained
      lots of wood debris, particularly twigs of coniferous trees. Potential
      nitrification was measured using the isotope-dilution technique, and potential
      denitrification was determined using the acetylene-inhibition technique in
      laboratory microcosm incubations. Nitrification rates were highest on the twigs.
      These rates were three and 100 times higher than in the sediment and on Eurasian
      watermilfoil, respectively. Potential denitrification rates were highest in the
      sediment. These rates were three times higher than on the twigs and 40 times
      higher than on Eurasian watermilfoil. The distribution of denitrifying bacteria
      was most likely due to the availability of organic material, with higher
      denitrification rates in the sediment than on surfaces in the water column. Our
      results indicate that denitrification, and particularly nitrification, in
      treatment wetlands could be significantly increased by addition of surfaces such
      as twigs.

PMID- 14674569
TI  - Effects of static vs. tidal hydrology on pollutant transformation in wetland
      sediments.
AB  - This work addressed effects of hydrology on biogeochemical processes relevant to
      pollutant chemical transformation in wetland sediments. Microcosms were designed
      to impose three hydrologic conditions on salt marsh sediments: (i) drained
      oxidized redox potenial (Eh); (ii) flooded-reduced Eh and, (iii) diurnal tide
      oscillating Eh. The test chemicals were N- and/or S-heterocycles (NSHs) including
      quinoxaline (1,4-benzodiazine), 2-methylquinoxaline(2-methyl-1,4-benzodiazine),
      2,3-dimethylquinoxalinen (2,3-dimethyl-1,4-benzodiazine), phenazine (2,3,5,6
      dibenzo-1,4-diazine), acridine (2,3,5,6-dibenzopyridine), dibenzothiophene (2,3,5
      dibenzothiophene), phenothiazine (dibenzo-1,4-thiazine), and phenanthridine (2,3
      benzoisoquinoline). Biogeochemical processes reflected the hydrologic conditions
      in ways analogous to field settings, e.g., Eh characteristics were drastically
      different: static (flooded and drained) systems had reduced (mu = -428 mV +/- 57)
      and oxidized (mu = +73 mV +/- 32) values, respectively, with no evidence of
      periodic variation while the tidal systems exhibited regularly oscillating Eh
      (amplitudes 40-250 mV). Sediment trace gases also corresponded to the Eh, with
      the major species detected being CO2 and H2O (drained, tidal) vs. CO2 + H2O +
      sulfides + methane (flooded). The NSH transformation rates were different in each
      hydrologic regime and decreased as follows: tidal > or = drained >> flooded.
      These results indicated that there were subtle differences in NSH processing in
      drained and tidal systems, but both of these systems transformed NSHs faster and
      to lower levels than flooded sediments. These data suggest that in situ
      remediation options that preserve wetland integrity and tidal hydrology can be as
      or more effective than static conditions that obtain in approaches such as
      impoundment and excavation-upland placement.

PMID- 14674571
TI  - Nitrification and denitrification rates of Everglades wetland soils along a
      phosphorus-impacted gradient.
AB  - Little information is available on the effect of phosphorus (P) enrichment on
      nitrogen (N) biogeochemical cycling in wetland soil. Of particular importance are
      the coupled nitrification-denitrification reactions that regulate the microbially
      mediated loss of N from wetland systems. Soils from the northern Florida
      Everglades have been affected by P loading from surface waters over the past 40
      years. Elevated P levels have been show to have an effect on the size and
      activity of the microbial pool and a decrease in the N to P ratio of the
      microbial biomass. The objective of the study was to determine if P enrichment in
      soils affected microbial activities related to nitrification and denitrification
      in these flooded, peat soils. Potential nitrification rates of soil and detritus
      were determined using constantly stirred reactors under aerobic conditions while
      denitrification rates were determined from anaerobic incubations of slurry.
      Nitrification rates showed two distinct linear phases, a slower initial rate,
      signifying activity of nitrifiers present, followed by a sharp increase in the
      NH4+ conversion rate indicative of maximum potential rates. Initial rates of
      nitrification were highest in the surficial detrital layer decreasing with soil
      depth and did not correlate to soil total P. The potential rates of nitrification
      were 13 times greater than the initial rates. Potential denitrification rates
      were highest in the detritus and 0- to 10-cm soil interval with significantly
      lower values in the 10- to 30-cm soil interval, significantly correlated to total
      P of the soil. A significant (P < 0.01) relationship was seen between potential
      denitrification rates and soil total P suggesting an increased rate of N removal
      from P-enriched regions of the northern Everglades.

PMID- 14674570
TI  - Accumulation, release, and solubility of arsenic, molybdenum, and vanadium in
      wetland sediments.
AB  - This study was undertaken to determine the fate of As, Mo, and V (trace elements,
      TEs) in the sediments of a constructed wetland in use for the remediation of
      potentially toxic trace element-contaminated agricultural drainwater. After three
      years of wetland operation, sediment cores were collected to determine changes in
      TE concentrations as a function of depth and the effects of varying water column
      depth. All TE concentrations were highest in the top 2 to 4 cm and decreased with
      depth. Molybdenum accumulated in the wetland sediments, up to levels of 32.5 +/-
      4.6, 30.2 +/- 8.9, and 59.3 +/- 26.1 mg kg(-1) in the top 1 cm of sediment at
      water depths of 15, 30, and 60 cm, respectively. In the top 2 cm of sediment, As
      accumulated (28.2 +/- 3.0 mg kg(-1)) only at the 60-cm water depth. Below 2 cm,
      as much as 10 mg kg(-1) of As was lost from the sediment at all water depths. In
      most cases, V concentrations decreased in the sediment. In this wetland system,
      the lowest redox potentials were found near the sediment surface and increased
      with depth. Thus, in general As, Mo, and V concentrations in the sediment were
      highest under more reducing conditions and lowest under more oxidizing
      conditions. Most of the accumulated Mo (73%) became water soluble on drying of
      samples. This has important implications for systems undergoing changes in redox
      status; for instance, if these wetland sediments are dried, potentially large
      amounts of Mo may be solubilized.

PMID- 14674572
TI  - The Web is more a social creation than a technical one.

PMID- 14674573
TI  - A world of no boundaries.
AB  - Ken Wilber's philosophy of no boundaries provides a backdrop for letting go of
      boundaries between art and science, research and practice, and nursing theories.
      Major nursing concepts are cited from a variety of theoretical persuasions to
      illustrate a statement of a unified perspective of the discipline. The author
      calls for exploration of a world of no boundaries in the expansion of nursing
      knowledge and practice.

PMID- 14674574
TI  - Measurement issues related to data collection on the World Wide Web.
AB  - As the World Wide Web has become more prominent as a mode of communication, it
      has opened up new possibilities for research data collection. This article
      identifies measurement issues that occur with Internet data collection that are
      relevant to qualitative and quantitative research approaches as they occurred in
      a triangulated Internet study of perimenopausal women with migraine headaches.
      Issues associated with quantitative data collection over the Internet include (a)
      selecting and designing Internet data collection protocols that adequately
      address study aims while also taking advantage of the Internet, (b) ensuring the
      reliability and validity of Internet data collected, (c) adapting quantitative
      paper-and-pencil data collection protocols for the Internet, (d) making Internet
      data collection practical for respondents and researchers, and (e) ensuring the
      quality of quantitative data collected. Qualitative data collection over the
      Internet needs to remain true to the philosophical stance of the qualitative
      approach selected. Researcher expertise in qualitative data collection must be
      combined with expertise in computer technology and information services if data
      are to be of ultimate quality The advantages and limitations of collecting
      qualitative data in real time or at a later time are explored, as well as
      approaches to enhance qualitative data collection over the Internet. It was
      concluded that like any research approach or method, Internet data collection
      requires considerable creativity, expertise, and planning to take advantage of
      the technology for the collection of reliable and valid research data.

PMID- 14674575
TI  - Research methodology for the Internet: external validity (generalizability).
AB  - The burgeoning use of the Internet for nursing research calls for a need to
      examine characteristics of electronic populations, and how they can be
      conceptualized relative to their physically based counterparts. The 1963 work of
      Campbell and Stanley, now 40 years old, is revisited in relation to external
      validity, and its applicability to today's world of quantitative and qualitative
      research. Internal and external differences in Internet populations are outlined,
      and a new threat to external validity is proposed: the threat of Networked
      Effects, which is composed of 4 subfactors: Co-occurring Interferences to
      Testing, Self-selection Mechanisms, Electronic Group Environments, and Cultural
      Differences. These Internet threats must be well understood when formulating
      research methodology.

PMID- 14674576
TI  - Using Internet discussion boards as virtual focus groups.
AB  - While the potential of Internet-based qualitative research methods is
      substantial, such methods are not without their problems. Some of these
      methodological challenges are unique to the medium, while others are similar to
      those of more traditional qualitative methods. This article presents some of
      these methodological challenges, and explores some of the issues involved in
      using on-line discussion boards as virtual focus groups in a study of
      perimenopausal women with migraines. Design of the study and its advantages and
      disadvantages are discussed, including the role of the moderator. Some of the
      problems encountered included potential for misunderstandings due to limits of
      written communications, and difficulty encouraging participation.

PMID- 14674577
TI  - Feminist issues in e-mail group discussion among cancer patients.
AB  - From a feminist perspective, issues in using e-mail group discussion among cancer
      patients are explored and discussed by analyzing a study on gender and ethnic
      differences in cancer pain experiences among cancer patients. First, the study is
      concisely described. Then, while considering the essential components of research
      from a feminist perspective, issues identified throughout the research process
      (intersubjectivity, lack of women's voices, reflexivity and contextuality,
      dependability, and adequacy and credibility) are discussed. Based on the
      discussion, implications for future feminist research using e-mail group
      discussion are proposed.

PMID- 14674578
TI  - Gentle hugs: Internet listservs as sources of support for women with lupus.
AB  - Systemic lupus erythematosus is a chronic autoimmune illness that usually affects
      women during their childbearing years. Women with lupus must learn to live with a
      variety of unpredictable symptoms, making a consistent source of support and
      information important for day-to-day illness management. For many women, the
      Internet fills this need. This article reports the findings of a qualitative
      study of 3 Internet listservs that provide support and information to the
      community of people living with lupus. Five thematic areas that describe the type
      of information and support available to listserv participants are described and
      the benefits of listserv participation are discussed.

PMID- 14674579
TI  - The discursive field of Web-based health research: implications for nursing
      research in cyberspace.
AB  - Web-based health research is a relatively new phenomenon. Its definition and
      conceptualization differs markedly as it is deployed within and across a complex
      array of discourses, with serious implications for nursing research and knowledge
      development. Web-based health research offers nurse researchers unique and
      abundant opportunities to provide leadership in the development and conduct of
      diverse modes of online health research. To appropriately avail themselves of
      such opportunities, however, nurse researchers must first address the significant
      ontological, epistemological, methodological, ethical, legal, and professional
      issues and concerns that nursing research in cyberspace raises.

PMID- 14674580
TI  - Joint toxicity of similarly and dissimilarly acting chemicals to Daphnia magna at
      different response levels.
AB  - The toxicity of two amines, nonylamine and decylamine, which have a narcotic
      effect on organisms, and ethylparathion (enzymatic inhibitor) on Daphnia magna
      has been studied when acting singly and in joint toxicity tests. This was done on
      the basis of an isobologram method where curves of constant response, i.e.,
      isoboles are plotted vs. the concentrations of the two toxicants. The
      concentrations that immobilized 50, 10, and 0% of the test population in 48 h
      (IC50-48h, IC10-48h, and IC0-48h) were calculated. It is shown that nonylamine
      decylamine mixtures follow a near concentration addition model of joint toxicity,
      while ethylparathion-decylamine mixtures follow a less than additive or near
      independent action model. The study was performed using three toxicity indices:
      additive index, sum of toxic units, and similarity parameter lambda. An analysis
      of the similarity parameter lambda is done to evaluate whether it has a constant
      value for IC50-48h, IC10-48h, and IC0-48h. The results suggest that it is quite
      probable that a constant value of lambda can be used to characterize all response
      levels, as the isoboles corresponding to the average value of the similarity
      parameter fit within the 95% confidence intervals of toxicant concentrations at
      all response levels. The average value of lambda is about 0.80 for the nonylamine
      decylamine test and 0.30 for the ethylparathion-decylamine test.

PMID- 14674581
TI  - Precision of dialysis (peeper) sampling of cadmium in marine sediment
      interstitial water.
AB  - Isolating and analyzing interstitial water (IW) during sediment toxicity tests
      enables researchers to relate concentrations of contaminants to responses of
      organisms, particularly when IW is a primary route of exposure to bioavailable
      contaminants by benthic dwelling organisms. We evaluate here the precision of
      sampling IW with the dialysis or 'peeper' method using sediments spiked with five
      different concentrations of cadmium. This method is one of several that are
      commonly used for collecting IW. Seven consecutive ten-day toxicity tests were
      conducted on these sediments and IW samples were collected at the end of each of
      these tests. Prior to each test initiation and insertion of IW samplers,
      sediments were allowed to equilibrate for seven days under flow-through
      conditions with filtered seawater. At the end of each ten-day testing period,
      peepers were retrieved, and IW cadmium measured. Data sets were organized by
      treatment and test number. Coefficients of variation (CV) for the six replicates
      for each sediment and testing period and for each sediment across testing periods
      (42 replicates) was used as a measure of sampling precision. CVs ranged from 25
      to 206% when individual testing periods were considered, but ranged from 39 to
      104% when concentrations for all testing periods were combined. However, after
      removal of outliers using Dixon's Criteria, the CVs improved and ranged from 6 to
      88%. These levels of variability are comparable to those reported by others. The
      variability shown is partially explained by artifacts associated with the
      dialysis procedure, primarily sample contamination. Further experiments were
      conducted that support our hypothesis that contamination of the peeper causes
      much of the variability observed. If method artifacts, especially contamination,
      are avoided the dialysis procedure can be a more effective means for sampling IW
      metal.

PMID- 14674582
TI  - Contaminants of concern in Dutch marine harbor sediments.
AB  - The status of the contamination of Dutch marine harbor sediments was reevaluated
      after a period in which emissions from point sources had been greatly reduced.
      Data on sediment chemistry from 1999 and 2000 were assessed against screening
      levels (SLs) selected from available sediment quality guidelines and representing
      a low probability of adverse biological effects. This yielded a ranking of the
      environmental hazard of 22 contaminants. Most of the sediments were silty
      material; every year 15 to 25 million m3 of such material is dredged from Dutch
      harbors. Some 34% of the volume exceeded one or more SLs. The contaminants of
      concern were tributyltin (TBT), mineral oil (petroleum hydrocarbons),
      polychlorinated biphenyls (PCBs), and mercury. The PCB and mercury contamination
      is the legacy of historic inputs; the TBT and mineral oil contamination is
      related to present-day shipping activity. Concentrations of trace metals, rare
      earth elements, organochlorine pesticides, and polycyclic aromatic hydrocarbons
      (PAHs) were low and apparently of minor environmental concern. It is concluded
      that the risk assessment would be improved by laboratory testing of adverse
      biological effects.

PMID- 14674583
TI  - Energization of Comamonas testosteroni ATCC 17454 for indicating toxic effects of
      chlorophenoxy herbicides.
AB  - The toxicity of chlorophenoxy herbicides to a bacterium, strongly related to the
      well-known species Delftia (formerly Comamonas) acidovorans that are able to
      detoxify these xenobiotics, was investigated. The oxidation of n-hexanol via
      alcohol dehydrogenases, coupled with the generation of ATP by electron transport
      phosphorylation (ETP), was used as an indicator for energy-toxic effects on the
      growth of Comamonas testosteroni ATCC 17454. Uncoupling--reductions in ATP
      synthesis accompanied by increased respiration--was found to be induced by 1 mM
      of the classic uncoupler 2,4-dinitrophenol (2,4-DNP) at pH 7.0 and 8.0. At pH 5.4
      and 6.0, the ATP synthesis and respiration were strongly inhibited by both 2,4
      DNP and the chlorophenoxy herbicides tested. In contrast, 5 mM of 2,4
      dichlorophenoxyacetic acid (2,4-D) and of 2-(2,4-dichlorophenoxy)-propanoic acid
      (2,4-DCPP) were required for detectable uncoupling effects--reduction of the P/O
      ratios by about 30%--at pH 7.0. These chemicals may have less uncoupling power
      because the concentration of their protonated (undissociated) forms (pKa values
      2.7 and 3.0) is an order of magnitude lower than that of 2,4-DNP (pKa = 4.0) at
      this pH value. Strong uncoupling accompanied by increased respiration, like that
      induced by 1 mM 2,4-DNP, was also caused by 5 mM 4-(2,4-dichlorophenoxy)-butyric
      acid (2,4-DCPB), which correlates with its high pKa value of 4.6. The order of
      toxicity of the chlorophenoxy herbicides (2,4-D < 2,4-DCPP < 2,4-DCPB) to the
      ETP, which correlates well with the lipophilicity of their undissociated forms
      (log P 2.7 < 3.4 < 3.5, respectively), was confirmed by measuring their capacity
      to inhibit the growth of Comamonas testosteroni ATCC 17454. The results show that
      energization via alcohol dehydrogenases can be used as an indicator for
      investigating energy-toxic effects of organics on the ETP and growth of
      chlorophenoxy herbicide-detoxifying bacteria.

PMID- 14674584
TI  - Effects of cysteine on the cytotoxicity of arsenic compounds.
AB  - Effects of cysteine on the cytotoxicity of arsenic compounds, such as arsenite,
      arsenate, methylarsonic acid (MMA), and dimethylarsinic acid (DMA), were
      investigated in cultured human HL-60 cells. Using adenosine triphosphate
      bioluminescence assay, the rank order of the mixtures of arsenicals with cysteine
      was: DMA > arsenite > arsenate > MMA. The IC50 of DMA with equimolar cysteine was
      approximately 7.7 microM, nearly two orders of magnitude lower than that of DMA
      alone. Apoptotic cells were examined by the TUNEL method, and cysteine was found
      to enhance the induction of apoptosis by arsenicals. Using LC-ICP-MS, trivalent
      arsenic was detected in the mixtures of arsenate, DMA, and MMA with cysteine.
      These results suggested that the trivalent arsenic in the mixtures of arsenicals
      with cysteine might account for the enhanced cytotoxicity as well as apoptosis,
      and that cysteine is involved in induction of the adverse effects of arsenicals
      in humans.

PMID- 14674585
TI  - Acute toxicity of methyl-parathion in wetland mesocosms: assessing the influence
      of aquatic plants using laboratory testing with Hyalella azteca.
AB  - Methyl-parathion (MeP) was introduced into constructed wetlands for the purpose
      of assessing the importance of distance from the source of contamination and the
      role of emergent vegetation on the acute toxicity to Hyalella azteca (Crustacea:
      Amphipoda). A vegetated (90% cover: mainly Juncus effuses) and a nonvegetated
      wetland (each with a water body of 50 x 5.5 x 0.2 m) were each exposed to a
      simulated MeP storm runoff event. H. azteca was exposed for 48 h in the
      laboratory to water samples taken from the wetlands at a distance of 5, 10, 20,
      and 40 m from the pesticide inlet 3 h, 24 h, 96 h, and 10 days following
      application. Methyl-parathion was detected throughout the nonvegetated wetland,
      whereas the pesticide was only transported halfway through the vegetated wetland.
      A repeated-measure three-way analysis of variance (ANOVA) using time, location,
      and vegetation indicated significantly lower toxicity in the vegetated wetland.
      Furthermore, the mortality decreased significantly with both increasing distance
      from the inlet and time (48-h LC50 +/- 95% CI: 9.0 +/- 0.3 microg/L). A
      significant three-way interaction of time x vegetation x location confirmed
      higher toxicity at the inlet area of the nonvegetated wetland immediately after
      contamination. Significant linear regressions of maximum mortality (independent
      of time) versus distance from the pesticide inlet indicated that 44 m of
      vegetated and 111 m of nonvegetated wetland would reduce H. azteca mortality to <
      or = 5%. These results suggest that vegetation contributes to reduced MeP effects
      in constructed wetlands.

PMID- 14674586
TI  - Induction of oxidative stress in the red macroalga Gracilaria tenuistipitata by
      pollutant metals.
AB  - Heavy metals are environmental pollutants that have the potential to induce
      severe stress-reactions in organisms on land as well as in the sea. We have
      studied effects of short term sublethal concentrations of copper (Cu2+) and
      cadmium (Cd2+) on the reactive oxygen metabolism of the marine red macroalga
      Gracilaria tenuistipitata. Additions of either 0.2 ppm Cu2+ or 1 ppm Cd2+ caused
      decreased growth (approximately 60%), increased oxidation of lipids and increased
      oxidative damage to proteins as shown by increased content of protein carbonyl
      groups. Together this strongly suggests an induction of oxidative stress. Cu2+
      caused more oxidative damage than Cd2+. As a response to the increased oxidative
      stress, addition of Cu2+ induced the activities of catalase, ascorbate
      peroxidase, and superoxide dismutase. In contrast, Cd2+ only caused increased
      catalase activity. Ten-fold lower concentrations of the metals did not cause an
      increase in enzyme activity. Both heavy metals also increased the content of the
      antioxidants beta-carotene and lutein. The results show that Cd2+ and, to a
      larger extent, Cu2+ induce oxidative stress in short-term experiments and the
      seaweed responds by increasing the activity of the reactive oxygen metabolism.

PMID- 14674587
TI  - Assessing the impact of triazine herbicides on organophosphate insecticide
      toxicity to the earthworm Eisenia fetida.
AB  - A standard Organization for Economic Cooperation and Development (OECD) filter
      paper test was used to assess the acute toxicity of chlorpyrifos, atrazine,
      cyanazine, and simazine to the earthworm Eisenia fetida. Acute toxicity of
      chlorpyrifos was also determined in combination with the three-triazine
      herbicides. Surprisingly, atrazine and cyanazine caused mortality at
      concentrations lower than chlorpyrifos. Atrazine and cyanazine also increased the
      toxicity of chlorpyrifos 7.9- and 2.2-fold, respectively. However, simazine
      caused no toxicity to the worms and did not affect chlorpyrifos toxicity in
      binary mixture experiments. Possible mechanisms for the greater-than-additive
      toxicity for the binary combinations of atrazine and cyanazine with chlorpyrifos
      were investigated, including changes in uptake and biotransformation rates of
      chlorpyrifos in the presence of atrazine. Uptake of chlorpyrifos into the worms
      decreased slightly when atrazine was present in the system, therefore eliminating
      increased uptake as a possible explanation for the increased toxicity. Body
      residue analysis of worms indicated increased metabolite formation, suggesting
      the greater-than-additive response may be due to increased biotransformation to
      more toxic oxon metabolites.

PMID- 14674588
TI  - DNA damage induced by copper on erythrocytes of gilthead sea bream Sparus aurata
      and mollusk Scapharca inaequivalvis.
AB  - Heavy metal pollution in rivers and its impact on aquatic ecosystems is a dynamic
      process. Fish are ideal indicators of heavy metal contamination in aquatic
      systems because they occupy different trophic levels and are of different sizes
      and ages. In particular, copper is an essential trace metal for living organisms
      and it is present in all natural waters and sediments. In this paper, we report
      data on the effect of copper on DNA erythrocytes from the teleost gilthead sea
      bream Sparus aurata and the bivalve mollusk Scapharca inaequivalvis. In
      particular, the effect of 0.1 ppm of Cu2+ on the nucleated erythrocytes was
      analyzed using the "comet assay." This test is a promising tool for estimation of
      DNA damage at the single cell level. The data obtained show that the in vivo
      treatment with 0.1 ppm of copper increased the susceptibility of DNA to be
      damaged. Exposure to Cu2+ produces a more evident effect on Sparus aurata, as all
      three comet parameters significantly increased (tail length, tail intensity, and
      tail moment). The higher comet parameters measured in Scapharca inaequivalvis
      compared to Sparus aurata could be due to the difference in stability of the
      respective hemoglobins. The comet assay could represent a useful test to evaluate
      the biological consequences of environmental contamination by metals on marine
      organisms.

PMID- 14674589
TI  - Effects of copper sulfate on ion balance and growth in tilapia larvae
      (Oreochromis mossambicus).
AB  - Newly hatched tilapia larvae were exposed to sublethal concentrations of Cu2+ (0,
      30, 50, and 100 microg/L) and lethal concentrations of Cu2+ (200 and 400
      microg/L) for 24-96 h. The interaction of the exposure dose and time was related
      to the Cu2+ accumulation rate, which showed a higher accumulation rate with
      sublethal concentrations of Cu2+ within 24 h compared to the other treatments.
      Furthermore, Cu2+ contents in the whole body of larvae significantly increased
      following Cu2+ exposure times up to 96 h. Cu2+ in the medium produced a dose
      response effect on Na+ and K+ contents in larvae after 96 h of exposure time.
      Changes in Ca2+ contents statistically significantly decreased and were shown to
      be dose-responsive for larval exposure times exceeding 72 h. Changes of Ca2+
      contents were more sensitive than those of Na+ and K+ with Cu2+ treatment of
      early larvae. Notably Na+ and K+ contents showed significant increases of 17-23%
      in larvae exposed to low concentrations of Cu2+ (30-50 microg/L) for 24-72 h as
      compared to control larvae. Cu2+ caused no significant effect on body Cl- content
      or osmolality except at 100 microg/L Cu2+ for 24 h in tilapia larvae as compared
      to the control. However, there was a restoration phenomenon in larvae exposed to
      100 microg/L Cu2+ for longer than 72 h. The water content of larvae exposed to
      Cu2+ for 96 h significantly decreased. The yolk absorption rate of tilapia larvae
      was significantly suppressed when they were exposed to Cu2+ medium containing 30,
      50, 100, 200, or 400 Cu2+ microg/L from 72 h post transfer. These results
      obviously show that larvae are sensitive to Cu2+ during early development.

PMID- 14674590
TI  - Bioaccumulation of benzo(a)pyrene from sediment by fathead minnows: effects of
      organic content, resuspension and metabolism.
AB  - The accumulation of 14C-benzo(a)pyrene (BaP) sorbed to sediment was examined in
      fathead minnows (Pimephales promelas) to compare uptake from sediment with a high
      organic carbon (OC) content (7.7%), to that with a low OC content (2%). Ingestion
      of sediments was quantified by co-labeling the sediment with 141Cerium, which was
      not assimilated by the fish. Results of this study indicated that (1)
      significantly greater quantities of BaP were dissolved in water over low-OC
      sediment, compared to water over high-OC sediment, (2) fish disturbed the
      sediment and increased the concentration of BaP in centrifuged (particle-free)
      water, (3) fish ingested significantly more of the low-OC sediment than high-OC
      sediment, perhaps in response to the lower food quality of the low-OC sediment,
      and (4) uptake of BaP from sediment ingestion contributed <3% of the total flux
      of BaP into the fish. Primarily as a result of the greater concentration of BaP
      in water, fish from the low-OC exposures had significantly higher rates of BaP
      accumulation. However, after 48 h the body burdens in these fish declined by 50%,
      likely due to the induction of MFO enzymes in response to accumulation of BaP. A
      smaller effect was apparent in the fish from the high-OC exposures, consistent
      with the lower dose of BaP they experienced. These results illustrate the
      complex, and sometime counterintuitive, interactions that affect the uptake and
      bioaccumulation of sediment-associated contaminants.

PMID- 14674591
TI  - Global pollution monitoring of PCBs and organochlorine pesticides using skipjack
      tuna as a bioindicator.
AB  - Concentrations of organochlorines (OCs) representing persistent organic
      pollutants (POPs), such as polychlorinated biphenyls (PCBs), dichlorodiphenyl
      trichloroethane and its metabolites (DDTs), chlordane compounds (CHLs),
      hexachlorocyclohexane isomers (HCHs), and hexachlorobenzene (HCB), were
      determined in the liver of skipjack tuna (Katsuwonus pelamis) collected from the
      offshore waters of various regions in the world (offshore waters around Japan,
      Taiwan, Philippines, Indonesia, Seychelles, and Brazil, and the Japan Sea, the
      East China Sea, the South China Sea, the Bay of Bengal, and the North Pacific
      Ocean). OCs were detected in livers of all of the skipjack tuna collected from
      the locations surveyed, supporting the thesis that there is widespread
      contamination of persistent OCs in the marine environment. Within a location, no
      significant relationship between growth-stage (body length and weight) and OC
      concentrations (lipid weight basis) was observed, and the OC residue levels were
      rather uniform among the individuals. Interestingly, the distribution of OC
      concentrations in skipjack tuna was similar to those in surface seawaters from
      which they were taken. These results suggest that OC concentrations in skipjack
      tuna could reflect the pollution levels in seawater from which they are collected
      and that this species is a suitable bioindicator for monitoring the global
      distribution of OCs in offshore waters and the open ocean. Concentrations of PCBs
      and CHLs in skipjack tuna were higher in offshore waters around Japan (up to 1100
      and 250 ng/g lipid wt, respectively), suggesting the presence of sources of PCBs
      and CHLs in Japan. High concentrations of DDTs and HCHs were observed in samples
      from the Japan Sea, the East China Sea, the South China Sea, and the Bay of
      Bengal (up to 1300 and 22 ng/g lipid wt, respectively). This result suggests
      recent use of technical DDT and HCH for agricultural and/or public health
      purposes in Russia, China, India, and some other developing Asian countries.
      Relatively high concentrations of PCBs, CHLs, HCHs, and HCB were also observed in
      samples collected from some locations in the middle of the Pacific Ocean,
      indicating the expansion of OC contamination on a global scale. Considering these
      facts, continuous studies monitoring these compounds in offshore waters and the
      open seas, using skipjack tuna as a bioindicator, are needed to further
      understand the future trend of contamination.

PMID- 14674592
TI  - Experimental study of blood lead kinetics in estuarine crocodiles (Crocodylus
      porosus) exposed to ingested lead shot.
AB  - A previous study of lead (Pb) contamination in estuarine crocodiles (Crocodylus
      porosus) in Kakadu National Park, Australia, found elevated Pb levels in bone and
      flesh from individuals caught in habitats where hunting with lead ammunition had
      occurred. Lead shot was suspected as the potential source of Pb in these animals.
      An investigation was designed to determine if crocodiles are capable of retaining
      and dissolving lead shot in their stomachs and absorbing the ionic Pb into the
      blood. Four of the six juvenile crocodiles (C. porosus) used in the experiment
      were fed an initial dose of five or ten lead shot each. Most of the lead shot
      were retained in the stomach over the 20-week experimental period, as confirmed
      by stomach lavage and radiography of the stomach region. From 13 to 30% of the
      original weight of individual lead shot had been eroded in that time. In vitro
      experiments confirmed that lead shot could be dissolved under conditions
      simulating those known for the crocodilian stomach. Blood Pb concentrations
      increased by an order of magnitude within a week after dosing three crocodiles
      with five lead shot each, and then attained steady-state equilibrium 5-20 weeks
      after dosing, with blood Pb steady-state levels ranging from 278 to 363
      microg/dL. The blood Pb concentration-time curves in these crocodiles followed a
      one-compartment model with first-order loss kinetics that yielded an apparent
      biological half-life for Pb in blood of about 3.4 days. Throughout the
      experiment, the crocodiles remained in apparent good physical condition and
      displayed no clinical signs of Pb toxicosis. These observations, together with
      the very high blood Pb levels that were sustained for several months, suggest
      that crocodilians may possess a relatively high degree of resistance to Pb
      toxicity.

PMID- 14674593
TI  - Egrets as monitors of trace-metal contamination in wetlands of Pakistan.
AB  - Environments in Pakistan are subject to increasing pollution, but previous
      studies were very scanty. During 1999 and 2000, we assessed trace element
      contamination at three wetlands, Karachi Harbour (with presumed industrial-urban
      pollution), Taunsa Barrage (agricultural pollution), and Haleji Lake (relatively
      unpolluted), using as indicators the eggs and the feathers of colonial
      waterbirds, particularly Little Egrets, their prey, and the sediments collected
      within their foraging areas. The concentrations of As, Cd, Cr, Pb, Hg, Mn, Se,
      and Zn were generally within the normal background level, and mostly below the
      threshold that may affect bird survival or reproduction. However, somewhat high
      concentrations were found in fish from Karachi, for Pb that was at levels that
      may harm fish reproduction, and for Hg that was at limit concentration for human
      consumption. Alarming concentrations were found for Cr and Se in sediments from
      Karachi, that were above the critical levels for contaminated soil, and Se in
      eggs, that may affect egret reproduction. The differences among the three
      wetlands were less marked than hypothesized. The egret species within the same
      area differed in the concentration of certain elements in their eggs, possibly
      because females may have foraged in different habitats before breeding, whereas
      no interspecies difference was found in chick feathers, presumably because their
      food had been collected in similar habitats around the colony. High
      bioaccumulation from sediments to organic samples occurred for Hg, while Cd, Se,
      and Zn exhibited low accumulation; for all these elements, feathers of predatory
      birds such as the egrets are the best indicators of environmental contamination.
      On the other hand, As and Cr did not bioaccumulate, and the sediments, or the
      organisms low in the food chain, like fish or crustaceans, are better indicators
      of their presence in the environment than predatory birds.

PMID- 14674594
TI  - Persistent organochlorine pollutants in liver of birds of different trophic
      levels from coastal areas of Campania, Italy.
AB  - Liver samples of 12 species of birds of different trophic levels, collected
      during the period 1998-2000 from coastal areas of the Campania region, Southern
      Italy, were analyzed for organochlorine pesticides (OCs), such as
      dichlorodiphenyltrichloroethane (DDT) and its metabolites, hexachlorobenzene
      (HCB), gamma-hexachlorocycloexane (gamma-HCH), aldrin, dieldrin, endrin, and the
      seven PCB "target" congeners, IUPAC Nos. 28, 52, 101, 118, 138, 153 and 180. p,p'
      DDE was present in all the samples analyzed, at concentrations ranging from 4 to
      4504 ng/g wet wt, which were much higher than those found for HCB, dieldrin, and
      p,p'-DDD. The concentrations of the others OCs were below the detection limit in
      all the samples. PCBs were found in all the bird species at levels ranging
      between 6 and 8431 ng/g wet wt. The hepta-, hexa-, and penta-chlorinated
      congeners 180, 153, 138, and 118 were predominant since, in almost all the
      species, they contributed to more than 98% of the total seven determined PCBs. No
      significant differences in mean concentrations of organochlorine pesticides are
      detected between single species or between species grouped according to their
      feeding habits (p > 0.05). However, p,p'-DDE levels were higher in carnivorous
      species than in omnivorous and insectivorous ones (carnivorous > omnivorous >
      insectivorous). Concentrations of total PCBs were significantly higher in
      omnivorous birds than in carnivorous (p < 0.01) and insectivorous ones (p <
      0.001), whereas carnivorous birds exhibited significantly higher total PCB levels
      than insectivorous ones (p < 0.01). Marked differences in total PCB
      concentrations were found also between single species (from p < 0.05 to p <
      0.001). Levels of OCs and PCBs were generally below the thresholds known to
      affect reproduction, however, mean hepatic concentrations of total PCBs in the
      yellow-legged herring gull (Larus cachinnans), black-headed gull (Larus
      ridibundus), and kestrel (Falcus tinnunculus) were far higher than those
      estimated to elicit immunosuppressive effects and possibly increase
      susceptibility to parasitoses.

PMID- 14674595
TI  - Acute effects of vanadate oligomers on heart, kidney, and liver histology in the
      Lusitanian toadfish (Halobatrachus didactylus).
AB  - The contribution of vanadate oligomers to the acute histological effects of
      vanadium was analyzed in the heart, kidney, and liver of Halobatrachus didactylus
      (Schneider, 1801). A sublethal vanadium dose (5 mM, 1 mL/kg) in the form of
      metavanadate (containing ortho and metameric species) or in the form of
      decavanadate (containing only decameric species) was intraperitoneally
      administered by injection, and specimens of H. didactylus were sacrificed at one
      and seven days postinjection. Sections of heart ventricle and renal and hepatic
      tissue were stained with hematoxylin-eosin and examined by light microscopy to
      identify vanadium-induced tissue injury. In addition, PicroSirius-stained
      ventricular sections were analyzed by bipolarized light microscopy to determine
      the fraction of myocardium occupied by the ventricular wall structural elements
      (collagen I, collagen III, and cardiac muscle). Both vanadate solutions produced
      similar effects in the renal tissue. Morphological alterations included damaged
      renal tubules showing disorganized epithelial cells in different states of
      necrosis. Reabsorbed renal tubules and hyperchromatic interstitial tissue were
      also observed. The hepatic tissue presented hyperchromatic and hypertrophied
      nuclei, along with necrotic and hypertrophied hepatocytes, and more severe
      changes were observed in the liver with exposure to decavanadate. Vanadate
      oligomers promoted evident tissue lesions in the kidney and liver, but not in the
      cardiac tissue. However, cardiac tissue structural changes were produced. For
      example, decavanadate induced a hypertrophy of the ventricle due to a decrease in
      the percentage of myocardium occupied by collagen fibers. In general,
      decavanadate was shown to be more toxic than metavanadate.

PMID- 14674596
TI  - Effect of sulfur dioxide inhalation on the glutathione redox system in mice and
      protective role of sea buckthorn seed oil.
AB  - This study investigated the effects of sulfur dioxide (SO2) inhalation and
      protection by sea buckthorn seed oil from oxidative damage caused by SO2 in male
      Kunming-strain mice. One approach was set up to study the effects of SO2
      inhalation on changes of the mice antioxidant defense system. SO2 at different
      concentrations (22 +/- 2, 64 +/- 3, and 148 +/- 23 mg/m3) was administered to
      animals in treatment groups for 7 days, 6 h per day, while control groups were
      exposed to filtered air under the same condition. The activities of glutathione-S
      transferase (GST) and glucose-6-phosphate dehydrogenase (G6PD) and the contents
      of reduced glutathione (GSH) in brain, lung, heart, liver, and kidney of mice
      were measured. In the case of inhalation of a SO2 concentration of 148 +/- 23
      mg/m3, the activities of GST and G6PD and contents of GSH in the brain, lung,
      heart, liver, and kidney were significantly decreased. Dose-dependent relations
      were found between various SO2-exposed concentrations and the activities of GST
      and G6PD and the content of GSH. Meanwhile another approach was taken to
      determine whether sea buckthorn seed oil could maintain the glutathione redox
      system and prevent the oxidative damage of lung induced by SO2. In groups given a
      high dosage (6 or 8 ml/kg) intraperitoneally, the level of TBARS (thiobarbituric
      acid-reactive substances) was decreased significantly (p < 0.05) by the injection
      of sea buckthorn seed oil, and the activity of GST was increased significantly (p
      < 0.05). Overall GST activity and TBARS level exhibited a significant negative
      correlation (r = 0.891, p < 0.05). The observations showed that SO2 inhalation
      resulted in a significant change in the glutathione redox system and indicated
      that sea buckthorn seed oil could contribute to the antioxidant effects in the
      case of SO2 exposure.

PMID- 14674597
TI  - Evasion of the immune system by adenoviruses.
AB  - Human adenoviruses (Ads) have the ability to transform primary cells, and certain
      Ads, the subgenus A adenoviruses such as Ad12, induce tumours in immunocompetent
      rodents. The oncogenic phenotype of the subgenus A adenoviruses is determined by
      the viral E1A oncogene. In order to generate tumours, Ad12-transformed cells must
      evade the cellular immune system of the host. Ad12 E1A gene products mediate
      transcriptional repression of several genes in the major histocompatibility
      complex (MHC) involved in antigen processing and presentation, resulting in
      evasion of cytotoxic T lymphocyte (CTL) killing of transformed cells. In this
      review, the molecular mechanisms of E1A-mediated transcriptional repression of
      MHC gene expression are described. In addition, evasion of natural killer (NK)
      cell killing by Ad-transformed cells is also considered.

PMID- 14674598
TI  - Immune evasion by adenovirus E3 proteins: exploitation of intracellular
      trafficking pathways.
AB  - Adenoviruses (Ads) are nonenveloped viruses which replicate and assemble in the
      nucleus. Therefore, viral membrane proteins are not directly required for their
      multiplication. Yet, all human Ads encode integral membrane proteins in the early
      transcription unit 3 (E3). Previous studies on subgenus C Ads demonstrated that
      most E3 proteins exhibit immunomodulatory functions. In this review we focus on
      the E3 membrane proteins, which appear to be primarily devoted to remove critical
      recognition structures for the host immune system from the cell surface. The
      molecular mechanism for removal depends on the E3 protein involved: E3/19K
      prevents expression of newly synthesized MHC molecules by inhibition of ER
      export, whereas E3/10.4-14.5K down-regulate apoptosis receptors by rerouting them
      into lysosomes. The viral proteins mediating these processes contain typical
      transport motifs, such as KKXX, YXXphi, or LL. E3/49K, another recently
      discovered E3 protein, may require such motifs to reach a processing compartment
      essential for its presumed immunomodulatory activity. Thus, E3 membrane proteins
      exploit the intracellular trafficking machinery for immune evasion.
      Conspicuously, many E3 membrane proteins from Ads other than subgenus C also
      contain putative transport motifs. Close inspection of surrounding amino acids
      suggests that many of these are likely to be functional. Therefore, Ads might
      harbor more E3 proteins that exploit intracellular trafficking pathways as a
      means to manipulate immunologically important key molecules. Differential
      expression of such functions by Ads of different subgenera may contribute to
      their differential pathogenesis. Thus, an unexpected link emerges between viral
      manipulation of intracellular transport pathways and immune evasion.

PMID- 14674599
TI  - The coxsackie-adenovirus receptor--a new receptor in the immunoglobulin family
      involved in cell adhesion.
AB  - The physiological and cell biological aspects of the Coxsackie-Adenovirus
      Receptor (CAR) is discussed in this review. The receptor obviously recognizes the
      group C adenoviruses in vivo, but also fibers from other groups except group B in
      vitro. The latter viruses seem to utilize a different receptor. The receptor
      accumulates at, or close to, the tight junction in polarized epithelial cells and
      probably functions as a cell-cell adhesion molecule. The cytoplasmic tail of the
      receptor is not required for virus attachment and uptake. Although there is a
      correlation between CAR and uptake of adenoviruses in several human tumor cells,
      evidence of an absolute requirement for integrins has not been forthcoming. The
      implication of these findings for adenovirus gene therapy is discussed.

PMID- 14674600
TI  - Mechanisms of E3 modulation of immune and inflammatory responses.
AB  - Adenoviruses contain genes that have evolved to control the host immune and
      inflammatory responses; however, it is not clear whether these genes function
      primarily to facilitate survival of the virus during acute infection or during
      its persistent phase. These issues have assumed greater importance as the use of
      adenoviruses as vectors for gene therapy has been expanded. This review will
      focus on the mechanism of immune evasion mediated by the proteins encoded within
      the early region 3 (E3) transcription region, which affect the functions of a
      number of cell surface receptors including Fas, intracellular cell signaling
      events involving NF-kappaB, and the secretion of pro-inflammatory molecules such
      as chemokines. The successful use of E3 genes in facilitating allogeneic
      transplantation and in preventing autoimmune diabetes in several transgenic mouse
      models will also be described.

PMID- 14674601
TI  - Modulation of oncogenic transformation by the human adenovirus E1A C-terminal
      region.
AB  - The E1A oncogene of human adenoviruses cooperates with other viral and cellular
      oncogenes in oncogenic transformation of primary and established cells. The N
      terminal half of E1A proteins that form specific protein complexes with pRb
      family and p300/CBP transcriptional regulators is essential for the transforming
      activities of E1A. Although the C-terminal half of E1A is dispensable for the
      transforming activities, it negatively modulates the oncogenic activities of the
      N-terminal region. Mutants of E1A lacking the C-terminal half or a short C
      terminal region exhibit a hyper-transforming phenotype in cooperative
      transformation assays with the activated ras oncogene. The E1A C-terminal region
      implicated in the oncogenesis-restraining activity interacts with a 48-kDa
      cellular phosphoprotein, CtBP, that functions as a transcriptional corepressor.
      It appears that the C-terminal region of E1A may suppress E1A-mediated oncogenic
      transformation by a dual mechanism of relieving repression cellular genes by
      CtBP, and also by antagonizing the oncogenic activities of the N-terminal half of
      E1A.

PMID- 14674602
TI  - Cell transformation by human adenoviruses.
AB  - The last 40 years of molecular biological investigations into human adenoviruses
      have contributed enormously to our understanding of the basic principles of
      normal and malignant cell growth. Much of this knowledge stems from analyses of
      their productive infection cycle in permissive host cells. Also, initial
      observations concerning the carcinogenic potential of human adenoviruses
      subsequently revealed decisive insights into the molecular mechanisms of the
      origins of cancer, and established adenoviruses as a model system for explaining
      virus-mediated transformation processes. Today it is well established that cell
      transformation by human adenoviruses is a multistep process involving several
      gene products encoded in early transcription units 1A (E1A) and 1B (E1B).
      Moreover, a large body of evidence now indicates that alternative or additional
      mechanisms are engaged in adenovirus-mediated oncogenic transformation involving
      gene products encoded in early region 4 (E4) as well as epigenetic changes
      resulting from viral DNA integration. In particular, detailed studies on the
      tumorigenic potential of subgroup D adenovirus type 9 (Ad9) E4 have now revealed
      a new pathway that points to a novel, general mechanism of virus-mediated
      oncogenesis. In this chapter, we summarize the current state of knowledge about
      the oncogenes and oncogene products of human adenoviruses, focusing particularly
      on recent findings concerning the transforming and oncogenic properties of viral
      proteins encoded in the E1B and E4 transcription units.

PMID- 14674603
TI  - Tumorigenesis by adenovirus type 12 in newborn Syrian hamsters.
AB  - Ad12 oncogenesis in hamsters has been studied in detail to provide the following
      new data in this tumor model. Cells in the Ad12-induced tumors, often thought to
      be of neuronal origin, actually exhibit mesenchymal and neuronal characteristics
      and are probably of an undifferentiated derivation. Their intraperitoneal spread
      upon intramuscular injection of Ad12 adds another important new aspect.
      Differences in the integration patterns among the tumors suggest clonal origins
      from individual transformation events. Ad12 gene expression in the tumors is
      determined, at least in part, by the patterns of DNA methylation imprinted de
      novo upon the integrated Ad12 genomes. Differential Ad12 gene expression
      patterns, which have previously not been described in tumors, are an important
      parameter in Ad12 oncogenesis. The availability of cellular DNA arrays has opened
      up unprecedented possibilities to document changes in cellular transcription
      patterns, particularly of cancer-specific genes. These patterns exhibit
      differences and similarities among the different Ad12-induced tumors. Among the
      cellular genes, which are expressed in the Ad12-induced tumors, many are cancer
      specific. We pursue the hypothesis that these alterations in cellular
      transcription patterns as a consequence of viral DNA integration and expression
      play an essential role in Ad12 oncogenesis.

PMID- 14674604
TI  - E1A-based determinants of oncogenicity in human adenovirus groups A and C.
AB  - A broad spectrum of genetic and molecular investigations carried out with group
      C, Ad2 and Ad5, and with group A, Ad12, have shown that early region1 (E1) gene
      products are sufficient for complete transformation of rodent cells in vitro by
      these viruses. During the past quarter century, the processes by which E1A
      proteins, in cooperation with E1B proteins, perturb the cell cycle and induce the
      transformed phenotype, have become well defined. Somewhat less understood is the
      basis for the differential oncogenicity of these two groups of viruses, and the
      processes by which the E1A proteins of Ad12 induce a tumorigenic phenotype in
      transformants resulting from infection of cells in vivo and in vitro. In this
      chapter we review previous findings and present new evidence which demonstrates
      that Ad12 E1A possesses two or more independent functions enabling it to induce
      tumors. One of these functions lies in its capacity to repress transcription of
      MHC class I genes, allowing the tumor cells to avoid lysis by cytotoxic T
      lymphocytes. We have shown that class I repression is mediated through increased
      binding of repressor COUP-TF and decreased binding of NF-kB to the class I
      enhancer. In addition to mediating immune escape, E1A also determines the
      susceptibility of transformants to Natural Killer (NK) cell lysis, and in this
      case, also, Ad12 transformants are not susceptible. By using Ad12 mutants
      containing chimeric E1A Ad12-Ad5 genes, point mutations, or a specific deletion,
      we have shown that the unique spacer region of Ad12 E1A is an oncogenic
      determinant, but is not required for transformation in vitro. Given that the E1A
      regions responsible for class I repression are first exon encoded, we have
      examined a set of cell lines transformed by these altered viruses, and have found
      that while they display greatly reduced tumorigenicity, they maintain a wildtype
      capacity to repress class I transcription. Whether the spacer contributes to NK
      evasion remains unresolved. Lastly, we discuss the properties of the Ad2/Ad5 E1A
      C-terminal negative modulator of tumorigenicity, and examine the effects on
      transformation, tumor induction and transformant tumorigenicity, when the Ad5
      negative modulator is placed by chimeric construction in Ad12 E1A.

PMID- 14674605
TI  - Replicating adenoviruses in cancer therapy.
AB  - The potential use of adenoviruses in therapy against cancer has evoked a rapidly
      moving field of research. Unlike conventional gene therapy vectors, oncolytic
      adenoviruses retain the ability to replicate. However, replication is restricted
      as much as possible to tumor cells, with the aim of eliminating these cells
      through viral cytotoxicity. The two key issues are to improve the efficiency of
      virus replication and cell killing while ensuring the specificity of these
      activities for tumor cells. Wild-type adenoviruses as such may already be usable
      for cancer therapy. Strategies to further improve efficiency and specificity
      include the partial or complete removal of viral genes. The idea is that
      functions carried out by the corresponding gene products are not required for
      replication in tumor cells, but are needed in normal cells. Accordingly, the
      removal of genes encoding E1B-55 kDa or E1B-19 kDa, or the mutation of E1A may
      improve the selective killing of tumor cells. On the other hand, the
      overexpression of the adenovirus death protein (ADP) may enhance viral spread and
      oncolytic efficiency. Other strategies to improve the specific oncolytic activity
      of replicating adenoviruses have been pursued. For instance, some promoters are
      active specifically in tumor cells, and these promoters were introduced into the
      viral genome, to regulate essential viral genes. Moreover, replicating viruses
      were engineered to express toxic proteins or drug converters. A number of these
      viruses have been tested successfully using tumor xenografts in nude mice as a
      model system. An oncolytic adenovirus lacking the E1B-55 kDa gene product, termed
      dl1520 or ONYX015, was injected into squamous cell carcinomas of head and neck in
      phase II clinical trials, and the results were encouraging when chemotherapy was
      applied in parallel. In the future, further progress might be achieved on the
      level of virus constructs, but also by refining and adjusting simultaneous
      conventional therapies, and by standardizing the assessment of the clinical
      outcome. Recent progress has been made towards the use of replicating virus
      constructs in cancer therapy. The goal of these developments is to remove
      cancerous cells from patients with the help of viruses that selectively replicate
      in these cells. These viruses are generally termed oncolytic viruses. Some
      convenient properties of adenovirus make this virus particularly useful for this
      purpose. It infects a large number of human cell types, especially epithelial
      cells, which give rise to the vast majority of human malignancies. It can be
      grown easily and to high titers, and the creation of virus recombinants is well
      established. Finally, a large body of basic research has already been carried out
      on this virus, facilitating its manipulation. Various approaches to use
      adenovirus as a cancer drug have been reviewed (Alemany et al. 1999a, 2000;
      Curiel 2000; Galanis et al. 2001b; Gromeier 2001; Heise and Kirn 2000; Kirn
      2000a; Kirn et al. 2001; Kirn and McCormick 1996; Smith and Chiocca 2000;
      Sunamura 2000; Wells 2000; Wodarz 2001). The aim of this chapter is to provide an
      integrated overview of these strategies.

PMID- 14674606
TI  - Adenovirus vectors: biology, design, and production.
AB  - The use of adenovirus as a gene transfer vehicle arose from early reports of
      recombinant viruses carrying heterologous DNA fragments. Adenovirus vectors offer
      many advantages for gene delivery: they are easy to propagate to high titers,
      they can infect most cell types regardless of their growth state, and in their
      most recent embodiments they can accommodate large DNA inserts. In this chapter,
      the development of adenovirus vectors is reviewed, from the use of so-called
      first-generation, E1-deleted viruses to the latest generation high-capacity,
      helper-dependent vectors. Examples of their use in the clinic are described, as
      are the current areas in which improvements to these vectors are being explored.

PMID- 14674607
TI  - Neuropeptides: general characteristics and neuropharmaceutical potential in
      treating CNS disorders.
AB  - The general characteristics of neuropeptides are discussed as a background for
      the understanding of their role in regulation of physiological systems. The
      extent of those systems that are crucially affected by neuropeptides is vast and
      the complexity of their interactions makes the clinical focus on a specific
      neuropeptide unsatisfactory. The clinical potential of neuropeptides affecting
      eating disorders, CNS behavioral disorders and the neuroregenerative and
      neuroprotective action of neuropeptides is discussed. It is probable that
      successful neuropeptide therapeutics will depend upon the application of
      translational and combinational research using various ingenious combinations of
      neuropeptides, their agonists and antagonists, neuropeptide receptor agonists and
      antagonists, improved methods of delivery and the development of peptides
      targeted to the genetic profile of individual patients.

PMID- 14674608
TI  - Structural and functional aspects of the blood-brain barrier.

PMID- 14674609
TI  - Peptide transport across the blood-brain barrier.

PMID- 14674611
TI  - Altering the properties of the blood-brain barrier: disruption and
      permeabilization.

PMID- 14674610
TI  - Intracranial delivery of proteins and peptides as a therapy for neurodegenerative
      diseases.
AB  - Parkinson's disease is characterized by a progressive degeneration of the
      substantia nigra pars compacta dopamine neurons that innervate the striatum.
      Unlike current treatments for PD, GDNF administration could potentially slow or
      halt the continued degeneration of nigral dopaminergic neurons. GDNF does not
      cross the blood-brain barrier and needs to be administered directly into the
      brain. Due to the progressive nature of PD, sustained delivery of trophic factors
      may be necessary for optimal, long-term neuronal effects. Novel methods for
      sustained delivery of GDNF into the nigrostriatal pathway are currently being
      studied in non-human primates, including computer-controlled infusion pumps.
      Using this approach, we have demonstrated that chronic infusions of nominally 7.5
      or 22.5 microg/day GDNF into the lateral ventricle, the putamen or the substantia
      nigra, using programmable pumps, promotes restoration of the nigrostriatal
      dopaminergic system and significantly improves motor functions in MPTP-lesioned
      rhesus monkeys with neural deficits modeling the terminal stages of PD and in
      aged rhesus monkeys modeling the early stages of PD. Based on the promising
      studies of the chronic effects of GDNF in non-human primate models of PD, a study
      was recently conducted in England on five advanced PD patients. Chronic GDNF
      infusion into the dorsal putamen, via programmable pumps, resulted in improved
      motor function in all patients and limited side effects were observed. However,
      while the data from this intraparenchymal clinical trial in humans look
      encouraging, extensive blinded efficacy trials will need to be conducted before
      it can be determined if chronic treatment with GDNF or other trophic molecules
      will prove useful in treating patients with PD.

PMID- 14674612
TI  - Modifying peptide properties by prodrug design for enhanced transport into the
      CNS.

PMID- 14674613
TI  - CNS-delivery via conjugation to biological carriers: physiological-based
      approaches.

PMID- 14674614
TI  - Peptide vectors as drug carriers.

PMID- 14674615
TI  - Waist-to-height ratio is a better obesity index than body mass index and waist-to
      hip ratio for predicting diabetes, hypertension and lipidemia.
AB  - Body mass index (BMI, kg/m.sq) and waist-to-hip ratio (WHR) are widely used as
      obesity indices for diabetes and cardiovascular risks. Lower adult height was
      related to diabetes and stroke. Waist-girth was proved important for visceral
      obesity. Incorporating waist-girth and height as waist-to-height ratio (WHtR), we
      reported earlier--"Waist-to-height ratio is an important predictor of
      hypertension and diabetes". We readdressed this index in a larger sample with two
      sample OGTT and lipid profiles. In a cluster sampling of 16,818 rural
      inhabitants, considering age > or = 20 y, 5713 subjects were found eligible. Of
      them, 4923 (M/F=2321/2602) volunteered for height, weight, blood pressure, waist
      girth and hip-girth. Fasting venous blood (5 ml) was drawn for plasma glucose,
      total cholesterol (T-chol), Triglycerides (TG) and high-density lipoprotien (HDL
      c). Overall, 1565 participants were undertaken for OGTT. The mean (SD) values of
      BMI, WHR and WHtR for subjects with diabetes and hypertension were significantly
      higher in either sex. The level significance was highest for WHtR. The prevalence
      of diabetes and hypertension increased significantly with higher quintiles of
      BMI, WHR and WHtR (chi sq values were largest in WHtR for both events). Partial
      correlation coefficients, controlling for age and sex, showed that BMI, WHR and
      WHtR significantly correlated with systolic and diastolic BP, FBG, T-chol and TG.
      In the entire correlation matrix, the 'r' values were the highest for WHtR.
      Taking diabetes and hypertension as dependent variables, logistic regression also
      showed the highest odds ratio in higher WHtR than BMI and WHR. We conclude that
      WHtR was proved again a valuable obesity index for predicting diabetes,
      hypertension and lipidemia.

PMID- 14674616
TI  - A study of histopathological pattern of neuromuscular disorders with clinico
      pathologic correlation.
AB  - Neuromuscular disorders are frequently seen in our clinical practice, though no
      certain data are available in this regard. This prospective, observational study
      which was done as a partial fulfillment of M.Phil (Pathology) degree in BSMMU.
      The study was undertaken at the Department of Pathology of Bangabandhu Shiekh
      Mujib Medical University from August 1999 to December 2000 to study the
      histomorphological pattern of neuromuscular disorders in a selected group of
      patients attending the neuromedicine, paediatrics and medicine departments of
      BSMMU. Another purpose of this study was to evaluate the diagnostic utility of
      muscle biopsy and clinico-pathologic correlation in the diagnosis of
      neuromuscular disorders. In this study, 55 cases of clinically diagnosed
      neuromuscular disorders of different kinds were included. Detail clinical history
      was obtained in all the cases. Clinical diagnosis were made on the basis of
      history, physical examination, reports of routine and special laboratory tests
      whenever available. Muscle biopsy was performed in all the cases and histological
      changes could be identified in 42 cases. In the remaining thirteen undiagnosed
      cases; eight cases revealed 'essentially normal muscle tissue' and five cases
      were inadequate for histological evaluation. So, the later two categories were
      not included for further analysis. Among the histologically diagnosed 42 cases of
      neuromuscular disorders, basically two different classes of diseases were
      identified; 1) Dystrophic type of muscular diseases 64.28% and 2) Non dystrophic
      (acquired) type of neuromuscular diseases such as Inflammatory myopathy 21.82%
      and Neurogenic muscular atrophy 7.14%. Within the dystrophic group the maximum
      number of diseases were diagnosed as Duchenne muscular dystrophy 21.49%, Primary
      myopathy-unclassified 19.04%, Baker muscular dystrophy 4.76% and Limb girdle
      muscular dystrophy 4.76% etc. Properly executed muscle biopsy is usually the most
      useful and effective technique for diagnosis of neuromuscular diseases in cases
      where immunohistochemical, genetic and electron microscopic examination is not
      possible.

PMID- 14674617
TI  - A clinical review of large cerebello pontile angle tumors.
AB  - The study was designed as retro-prospective and the study period was 3.5 years. A
      total of 66 (42 prospective and 24 retrospective) consecutive patients were
      included in the study. The commonest tumor in CPA is the Schwannoma (76%)
      followed by Meningioma (13.3%) and Epidermoid (4.44%). Unusual forms are
      Ependymoma and Hemangiopericytoma. Amongst the troublesome clinical features
      headache, hearing loss, vertigo and imbalance, vomiting and tinnitus were more
      important besides visual failure and features of lower cranial nerve involvement.
      The objective of the study is to "Review the Large Cerebello Pontile Angle tumors
      clinically". In this study 66 large CPA tumors were included and analyzed.
      Analysis of variance (ANOVA) was implied for the test of significance. On the
      whole, n=66 Schwannoma represents 76.70% and Meningioma 15.38%. Of these there
      are 45 cases with histological verification. The most common presenting (average
      duration is 1.3 years) symptoms were Headache (94.54%) and Hearing loss of
      varying grade (85.45%). Vertigo or imbalance was present in 67.27% cases.
      Vomiting was found in 54.54% of the times and difficulties in deglutition or
      voice change were complained of in 29.09% cases. Tinnitus was found only in
      27.27% cases and it was the complaint mostly in lower diameter tumors. By maximum
      diameter, there were 24 cases measuring 3-4 cm, 15 more than 4 cm and only one
      case <3 cm sized tumors. Volume-wise tumors with volume <10 cc were 5 cases, 10
      20 cc were 10, 20-30 cc were 13, 30-40 cc were 6 and >40 cc were 6. Similarly
      tumor volume and posterior fossa volume ratio was as follows: <10% were 6 cases,
      10-20% were 15 cases, 20-30% were 7 cases and >30% were 6 cases. Amongst the
      schwannomas, the consistency of the tumor has been shown to be important factor
      for LCN involvement. The softer variety involved LCN more often than the harder
      (p<0.05). The involvement of the different groups of lower cranial nerve ranged
      from 7% to 92%.

PMID- 14674618
TI  - Evaluation & management of clinically labeled carcinoma head of the pancreas--a
      prospective study of 60 patients.
AB  - Carcinoma head of the pancreas are assessed by clinical examination, imaging,
      Endoscopic Retrograde Cholangio Pancreatography (ERCP), Fine Needle Aspiration
      Cytology (FNAC) and finally by laparotomy. Nevertheless still there is a dilemma
      in labeling these patients as having inoperable cancer pancreas because operable
      lesions may be wrongly labeled as inoperable or benign lesion may be thought to
      be malignant. The aim of this study is to evaluate these patients who present
      with clinical features of inoperable carcinoma of pancreas and to assess their
      status of inoperability. Efforts were taken to explore the possibilities of
      curative resection. If found inoperable, then tissue or cytological sampling of
      the lesion and the alternative palliation therapy offered to them. Palliative
      surgery and respective analysis of data was done in 60 patients with clinically
      labeled carcinoma head of the pancreas. Laparotomy was done for--(i) Assessment
      of inoperability, (ii) tissue or cytological sampling and (iii) Bilioenteric and
      gastro enteric bypass. The tumor was considered to be inoperable by peroperative
      assessment & trial dissection when it invaded the surrounding vital structure.
      Histological confirmation was made by intraoperative core needle biopsy; shave
      biopsy, biopsy of hepatic and lymph node metastasis. Cytological sampling was
      done by transduodenal and intralesional FNAC. Hepaticojejunostomy or
      Cholecystojejunostomy, Gastrojejunostomy and enteroenterostomy were performed as
      palliative procedure in all patients. Chemical splanchinectomy was performed in
      25 patients. Twenty patients were diagnosed to have carcinoma by Endoscopic
      biopsy. In remaining 40 patients, peroperative tissue biopsy and cytological
      sampling yielded pancreatic carcinoma in 16 (40.0%), chronic pancreatitis in 6
      (15.0%), pancreatic tuberculosis in 5 (12.5%), pancreatic non Hodgkin's lymphoma
      in 3 (7.5%) and metastatic pancreatic cancer in 2 (5.0%). However, it failed to
      reveal any definitive diagnosis in 8 (20.0%) patients. These interesting findings
      changed the preoperative diagnosis and guided us to plan the surgical procedure
      for cancerous and non-cancerous patients accordingly.

PMID- 14674619
TI  - Use of Wigglesworth classification for the assessment of perinatal mortality in
      Bangladesh--a preliminary study.
AB  - The Wigglesworth pathophysiological classification was used to analyse perinatal
      deaths occurring in 5 health centres in Bangladesh. The aims were to assess the
      feasibility of this classification, to determine the causes of perinatal deaths
      and thereby to identify the areas in need of intervention. A total of 8058 births
      were recorded at 5 centres during the period of 11 months from mid-January to mid
      December 2001. There were 1069 deaths in the perinatal period. Stillbirths were
      slightly more frequent (53.5%) than early neonatal deaths (46.5%). Among the
      stillbirths, fresh stillbirths predominated over normally formed macerated ones
      at all centers except BIRDEM, where the majority (52.5%) was macerated. The
      majority (71.6%) of perinatal deaths were in the groups comprising asphyxial
      conditions (46.8%), conditions associated with immaturity (13.3%), and normally
      formed macerated stillbirths (NFMSB, 11.5%). In the group, 'other specific
      conditions' which was responsible for 9.3% of perinatal deaths, all but one case
      was attributed to sepsis. When the cases were subdivided by birth groups,
      asphyxia predominated in all but the <1000g group, in whom immaturity was
      responsible. Conditions associated with immaturity were second highest in number.
      The majority of the perinatal deaths (83.4%) was in babies less than 2500g. The
      study has shown that the Wigglesworth classification can be used in different
      types of health facilities in Bangladesh by doctors, nurses and midwives. The
      areas which need intervention are antepartum care, obstetric and newborn care
      practices, and environmental factors responsible for the high prevalence of
      prematurity and low birth weight.

PMID- 14674620
TI  - Newborn anthropometry and its relationship with maternal factors.
AB  - A cross sectional study was conducted in a public maternity hospital, Dhaka,
      Bangladesh on 316 pregnant women and their newborns. The study aimed at examining
      the relationship between birth weight and maternal sociodemographic,
      anthropometric and haematological factors. The study revealed that about 15% of
      babies were of low birth weight (LWB). The mean birth weight was found to be 2889
      +/- 468g. The LBW was more common in younger (< 20 years) and older (> or = 30
      years) mothers, low income group, day labourer and those with little or no
      education. The mean birth weight of male babies was on an average 138g more than
      that of female babies (p < 0.032). The babies of the mothers who had at least
      three antenatal visits, found to be 191g heavier than those who had less than
      three or no visit. The study showed that birth weight increased linearly as
      gestational age increased. The mean birth weight of babies of primi para was 107g
      less than those of multi para. The incidence of LBW were found to be 23.3% and
      10.4% respectively for maternal heamoglobin level of < 9g/dl and > or = 12g/dl.
      It was revealed that higher maternal anthropometric means were associated with
      higher birth weights. Logistic regression analysis supports that the gestational
      age at birth, maternal haemoglobin level and post partum weight were the
      important determinants of low birth weight.

PMID- 14674621
TI  - Risk factors associated with preterm labour.
AB  - A Prospective case control study was conducted in a tertiary hospital in Northern
      India to determine the risk factors associated with preterm labour. Ninety four
      consecutive patients with preterm spontaneous labour were selected as cases and
      188 patients with term spontaneous labour as control. The incidence of preterm
      labour was found to be 23.3%. The cases were older, shorter and lighter than
      controls. They had lower body mass index (BMI) and mid arm circumference (MAC).
      They belonged to significantly lower income group and their educational status
      was lower. Mean pregnancy order was higher and mean parity was lower amongst the
      cases. Mean birth weight and apgar score of the babies were lower. Maternal
      weight <45 kg (OR 4.9), height <150 cm (OR 3.4), BMI <19 kg/m2 (OR 2.91), MAC <20
      cm (OR 7.78), education <5 year (OR 2.73), income <2000 rupees (OR 5.05) and
      birth interval <12 months (OR 6.39) were significant risk factors for preterm
      labour.

PMID- 14674622
TI  - Construction of fetal charts for biparietal diameter, fetal abdominal
      circumference and femur length in Bangladeshi population.
AB  - Infants born for small for date (SFD) fetuses have an increased risk of perinatal
      mortality and morbidity. Different methods have been applied to identify these
      fetuses including history, clinical examination and ultrasonography.
      Ultrasonography has a better predictive value and majority of such fetuses can be
      identified. Measurements of the fetal biparietal diameter (BPD), abdominal
      circumference (AC) and femur length (FL) charts are widely used in dating
      pregnancies and follow-up of pregnant women in assessing fetal growth,
      identification of small for date (SFD) and growth retarded fetuses. This
      prospective study was performed to construct fetal chart for BPD, AC and FL at
      different gestational weeks from the Bangladeshi pregnant women. Seven hundred
      and ten women had ultrasonic measurements of fetal BPD, AC and FL between 12 to
      42 weeks of pregnancy. Centiles, mean and the standard deviation (SD) were
      calculated for BPD, AC and FL. Mean maternal age was 24.73 +/- 4.48 (Mean +/- SD)
      and 310 (43.7%) were primigravidae. There was a gradual increase of the BPD
      (outer-inner), AC and FL measurements of 5th, 10th, 50th and 90th Centiles upto
      38th weeks of gestation with a gradual increase of SD showing increasing
      dispersion of data. In cases of BPD and AC, After 38th weeks of gestation the
      Centiles showed a slower growth rate towards 42 weeks of pregnancy. This slower
      growth rate from 38 weeks of pregnancy was not noted in case of femur length.
      Fetal charts with the raw data for each measurement with superimposed fitted
      lines derived from polynomial (quadratic) regression were constructed. Quadratic
      model showed good fit to the data during construction of fetal charts. The new
      fetal measurement charts of BPD, AC and FL are unique for the Bangladeshi
      population and have not been found similar in the later weeks of pregnancy to
      those published for other Caucasian populations. These charts will help the
      clinicians and sonographers in dating pregnancy, identifying SFD and growth
      retarded fetuses.

PMID- 14674623
TI  - High density lipoprotein can modulate the inhibitory effect of oxLDL on
      prostacyclin generation by rat aorta in vitro.
AB  - To examine the effect of oxidized low density lipoprotein (oxLDL) on prostacyclin
      (PGI2) generation by rat aorta in vitro and whether high density lipoprotein
      (HDL) has any protective effect against the inhibition of PGI2 generation induced
      by oxLDL is the objective of this study. Preincubation of aortas with oxLDL
      resulted in significant inhibition of PGI2 generation compared to preincubation
      with normal low density lipoprotein (nLDL) or buffer only. The inhibitory effect
      of oxLDL resided in its lipid moiety while the lipid fraction of nLDL showed no
      effect. Aortas preincubated with 10 microg/ml of lyso phosphatidycholine (lyso
      PC) also showed 30% inhibition of PGI2 generation, indicating that lyso PC was
      among the lipid components of oxLDL which inhibited PGI2 generation.
      Preincubation of aortas with a mixture of HDL and oxLDL at a ratio of 10:1 showed
      a significant recovery of PGI2 generation compared to aortas preincubated with
      only oxLDL, indicating a protective role for HDL. When HDL was incubated with
      oxLDL the transfer of lyso PC from oxLDL to HDL suggested that HDL trapped lyso
      PC from oxLDL thus preventing it from acting on the aorta. However, when a
      mixture of HDL and oxLDL at a ratio of 3:1 was preincubated with aortas, no
      protective effect of HDL was observed. Preincubation of aortas with a mixture of
      HDL plus oxLDL at a ratio of 8:1, which was incubated for 1 h at 37 degrees C,
      produced significantly less PGI2 than aortas preincubated only with oxLDL,
      indicating that HDL under these conditions was not protective but even enhanced
      the inhibitory effect of oxLDL. Similarly, aortas preincubated with HDL plus
      whole oxLDL (at a ratio of 10:1); containing all the small molecular weight
      oxidation products and characterized by high levels of thiobarbituric acid
      reactive substance (TBARS) and lipid hydroperoxides; produced significantly less
      PGI2 than aortas preincubated with whole oxLDL. These results were evaluated in
      light of possible modification of HDL by oxLDL and its lipid oxidation products
      such as aldehydes and lipid peroxides. The modified HDL can add more lipid
      peroxides and increase the effectiveness of lipid peroxides originally present in
      oxLDL.

PMID- 14674624
TI  - Regulation of cell growth by selective COX-2 inhibitors in oral carcinoma cell
      lines.
AB  - Evidence indicates that NSAIDs that inhibit prostaglandin (PG) synthesis can
      reduce the incidence of colorectal cancers and that inhibition of cyclooxygenase
      2 (COX-2) may be the underlying mechanism. The objective of this study was to
      investigate this putative mechanism by examining the effect of selective COX-2
      inhibitors (Celebrex, DFU, NS-398) and COX-1 inhibitors (Aspirin) on the growth
      of two human oral carcinoma cell lines (OEC-M1 and KB) and one normal fibroblast
      cell line (NF). We found that the growth of OEC-M1 cells could be significantly
      inhibited by DFU concentrations above 30 microM (31%) after 4 days, and above 50
      microM (35%) after 2 days in culture; by Celebrex at concentrations above 20
      microM (52%) after 6 days, above 30 microM (36%) after 5 days, and above 40
      microM (33%) after 4 days in culture; and by NS-398 above 1 microM (30%) after 6
      days, and above 10 microM (35%) after 5 days in culture. The growth of KB cells
      could be significantly inhibited by DFU concentrations above 10 microM (33%)
      after 6 days, above 20 microM (35%) after 4 days in culture; and by Celebrex at
      concentrations above 10 microM (33%) after 5 days, and above 50 microM (30%)
      after 4 days in culture; and by NS-398 above 1 microM (45%) after 5 days, above
      20 microM (36%) after 4 days in culture. The growth of NF cells could be
      significantly inhibited by DFU above 30 microM (45%) after 6 days, and above 40
      microM (32%) after 3 days in culture, and by Celebrex at concentrations above 10
      microM (42%) after 6 days, above 30 microM (31%) after 4 days, above 50 microM
      (32%) after 3 days in culture, and by NS-398 above 0.1 microM (35%) after 4 days,
      and above 1 microM (32%) after 3 days in culture. The growth-inhibitory
      concentration (IC50) values for DFU on OEC-M1, KB, and NF cells were about 39.1,
      14.8, and 42.9 microM at 144 h, respectively, and on KB was about 45.2 microM at
      120 h. The IC50 values for Celebrex on OEC-M1, KB, and NF cells were about 19.1,
      8.6, and 15.8 microM at 144 h, respectively, and on KB and NF were about 27.7 and
      35.3 microM, respectively, at 120 h. The IC50 values for NS-398 on OEC-M1, KB,
      and NF were about 18.9, 0.7 and 1 microM, respectively, at 144 h; on KB and NF
      values were about 10.8 and 1.4 microM, respectively, at 120 h and on KB and NF
      were about 26.6 and 4.1 microM, respectively, at 96 h. The results show that the
      growth of these cell lines is inhibited by three COX-2 selective inhibitors but
      not by any COX-1 selective inhibitors. These findings suggest that COX-2 may play
      an important role in the generation of biochemical mediators that stimulate the
      growth of human oral cancer and normal fibroblast cell lines.

PMID- 14674625
TI  - Lipoxygenase inhibitors enhance tumor suppressive effects of jun proteins on v
      myb-transformed monoblasts BM2.
AB  - Inhibitors of arachidonic acid (AA) conversion were described as suppressors of
      proliferation and inducers of differentiation of various leukemic cells. Certain
      AA metabolites have been shown to cooperate with Jun proteins that are important
      factors controlling cell proliferation, differentiation and apoptosis. Using
      lipoxygenase (LOX) inhibitors of various specifity we studied possible
      participation of lipoxygenase pathway in regulation of proliferation and
      apoptosis of v-myb-transformed chicken monoblasts BM2 and its functional
      interaction with Jun proteins. We found that nordihydroguaiaretic acid (NDGA) and
      esculetin (Esc) negatively regulate proliferation of BM2 cells causing
      accumulation in either G0/G1-phase (nordihydroguaiaretic acid) or S-phase
      (esculetin) of the cell cycle. BM2 cells can be also induced to undergo growth
      arrest and partial differentiation by ectopic expression of Jun proteins. We
      demonstrated that lipoxygenase inhibitors further enforce tumor suppressive
      capabilities of Jun proteins by inducing either more efficient cell cycle block
      and/or apoptosis in BM2 cells. This suggests that there is a cross-talk between
      the lipoxygenase- and Jun-directed pathways in regulation of differentiation and
      proliferation of monoblastic cells. Thus pharmacologic agents that specifically
      block lipoxygenase-catalyzed activity and enforce the effects of differentiation
      inducers may be important components in anti-tumor therapies.

PMID- 14674626
TI  - Exogenous prostaglandin F2alpha as a mediator in the regulation of silkworm
      growth and silk gland genome.
AB  - Prostaglandins are locally acting hormones that have remarkable variety of
      physiological functions. They are rapidly synthesized in several types of
      vertebrate cells as oxygenated metabolites of arachidonic acid in response to
      various stimuli. In many insect species they are biosynthesized in fat body and
      hemocytes mainly in response to bacterial infections. In the present study, we
      administered synthetic analog of prostaglandin F2alpha, the most prominent of the
      prostaglandins to the 48 h old fifth instar silkworm, Bombyx mori L. at a single
      dose of 4 microg per larva to study its effects on the larval growth pattern and
      silk synthesis. The possible role of PGF2alpha at altering the quantum of silk
      synthesis by controlling the silk gene expression was also studied. The genomic
      DNA was isolated from the posterior silk gland on Days 5 and 7 of the fifth
      instar from the prostaglandin treated and the control larvae and were random
      amplified with arbitrary primers. The result presented notable variation in the
      amplified product suggesting the participation of PGF2alpha in the silk
      biosynthesis controlling the silk gene expression. The feeding period of treated
      larvae was unaffected while the cocoon characters exhibited considerable
      improvement. The filament traits also were improved notably in the treated
      larvae. The participation of PGF2alpha analog in the silk biosynthetic process
      with its physiological and molecular implications are discussed.

PMID- 14674627
TI  - Tissue-specific ceramide response in the chronically hypoxic rat model mimicking
      cyanotic heart disease.
AB  - BACKGROUND AND OBJECTIVE: Acute hypoxia is associated with apoptosis and increase
      in ceramide levels in various organs. To assess the effect of chronic hypoxia on
      ceramide accumulation in the lungs and kidneys, we utilized an animal model
      mimicking cyanotic heart disease. METHODS: Rats were placed in a hypoxic
      environment at birth and oxygen levels were maintained at 10% in an air-tight
      Plexiglas chamber. Controls remained in room air. Animals were sacrificed and the
      lung and kidneys were harvested and weighed at 1 and 4 weeks, respectively.
      Ceramide levels were measured using a modified diacylglycerol kinase assay.
      RESULTS: Significant polycythemia developed in the hypoxic rats at 1 and 4 weeks.
      Indexed lung and kidney masses were significantly increased in the hypoxic
      animals as compared to controls at 1 and 4 weeks, respectively. The ceramide
      levels in the hypoxic lungs and kidneys were not significantly different from
      control groups at 1 and 4 weeks. [Ceramide/phosphate ratio in the kidneys was
      1.28 +/- 0.17 (C) versus 1.18 +/- 0.12 (H) at 1 week; P = 0.39, and 1.46 +/- 0.08
      (C) versus 1.33 +/- 0.15 (H) at 4 weeks (P = 0.44)] and [ceramide/phosphate ratio
      (pmol/nmol) in the lungs was 2.29 +/- 0.14 (C) versus 1.98 +/- 0.12 (H) at 1 week
      (P = 0.17), and 2.42 +/- 0.16 (C) versus 2.30 +/- 0.05 (H) at 4 weeks, P = 0.34].
      CONCLUSION: The response of lungs and kidneys to chronic hypoxia includes
      increase in indexed mass and lack of ceramide accumulation. This is similar to
      the response previously reported in the chronically hypoxic brain and heart.
      Thus, various organs appear to have similar ceramide response pattern to chronic
      hypoxia.

PMID- 14674628
TI  - Moving and looming stimuli capture attention.
AB  - Attention capture is often operationally defined as speeded search performance
      when an otherwise nonpredictive stimulus happens to be the target of a visual
      search. That is, if a stimulus captures attention, it should be searched with
      priority even when it is irrelevant to the task. Given this definition, only the
      abrupt appearance of a new object (see, e.g., Jonides & Yantis, 1988) and one
      type of luminance contrast change (Enns, Austen, Di Lollo, Rauschenberger, &
      Yantis, 2001) have been shown to strongly capture attention. We show that
      translating and looming stimuli also capture attention. This phenomenon does not
      occur for all dynamic events: We also show that receding stimuli do not attract
      attention. Although the sorts of dynamic events that capture attention do not fit
      neatly into a single category, we speculate that stimuli that signal potentially
      behaviorally urgent events are more likely to receive attentional priority.

PMID- 14674629
TI  - Motion adaptation shifts apparent position without the motion aftereffect.
AB  - Adaptation to motion can produce effects on both the perceived motion (the motion
      aftereffect) and the position (McGraw, Whitaker, Skillen, & Chung, 2002; Nishida
      & Johnston, 1999; Snowden, 1998; Whitaker, McGraw, & Pearson, 1999) of a
      subsequently viewed test stimulus. The position shift can be interpreted as a
      consequence of the motion aftereffect. For example, as the motion within a
      stationary aperture creates the impression that the aperture is shifted in
      position (De Valois & De Valois, 1991; Hayes, 2000; Ramachandran & Anstis, 1990),
      the motion aftereffect may generate a shift in perceived position of the test
      pattern simply because of the illusory motion it generates on the pattern.
      However, here we show a different aftereffect of motion adaptation that causes a
      shift in the apparent position of an object even when the object appears
      stationary and is located several degrees from the adapted region. This position
      aftereffect of motion reveals a new form of motion adaptation--one that does not
      result in a motion aftereffect--and suggests that motion and position signals are
      processed independently but then interact at a higher stage of processing.

PMID- 14674630
TI  - Time course of melody recognition: a gating paradigm study.
AB  - Recognizing a well-known melody (e.g., one's national anthem) is not an all-or
      none process. Instead, recognition develops progressively while the melody
      unfolds over time. To examine which factors govern the time course of this
      recognition process, the gating paradigm, initially designed to study auditory
      word recognition, was adapted to music. Musicians and nonmusicians were presented
      with segments of increasing duration of familiar and unfamiliar melodies (i.e.,
      the first note, then the first two notes, then the first three notes, and so
      forth). Recognition was assessed after each segment either by requiring
      participants to provide a familiarity judgment (Experiment 1) or by asking them
      to sing the melody that they thought had been presented (Experiment 2). In
      general, the more familiar the melody, the fewer the notes required for
      recognition. Musicians judged music's familiarity within fewer notes than did
      nonmusicians, whereas the reverse situation (i.e., musicians were slower than
      nonmusicians) occurred when a sung response was requested. However, both
      musicians and nonmusicians appeared to segment melodies into the same perceptual
      units (i.e., motives) in order to access the correct representation in memory.
      These results are interpreted in light of the cohort model (Marslen-Wilson,
      1987), as applied to the music domain.

PMID- 14674631
TI  - On the (non)categorical perception of lexical tones.
AB  - Identification and discrimination of lexical tones in Cantonese were compared in
      the context of a traditional categorical perception paradigm. Three lexical tone
      continua were used: one ranging from low level to high level, one from high
      rising to high level, and one from low falling to high rising. Identification
      data showed steep slopes at category boundaries, suggesting that lexical tones
      are perceived categorically. In contrast, discrimination curves generally showed
      much weaker evidence for categorical perception. Subsequent investigation showed
      that the presence of a tonal context played a strong role in the identification
      of target tones and less of a role in discrimination. The results are consistent
      with the hypothesis that tonal category boundaries are determined by a
      combination of regions of natural auditory sensitivity and the influence of
      linguistic experience.

PMID- 14674632
TI  - The influence of the acoustic context on vertical sound localization in the
      median plane.
AB  - The influence of background sounds (frames) on vertical localization of single
      sound sources (targets) was examined in four experiments. Loudspeakers (five
      targets and four frames) were positioned in the median plane, ranging from +30
      degrees to -30 degrees above and below the subject's ear level. The subjects
      determined the vertical position of the targets by either verbal judgments or
      manual pointing. Frame and target sounds were presented concurrently or
      successively with a 1-sec interval; both consisted of (1) 300-Hz square waves,
      (2) noise, or (3) targets of noise and frames of 300-Hz square waves.
      Particularly in the second condition, the subjects consistently shifted the
      apparent target positions away from the frame locations. This contrast effect
      persisted even 1 sec after the offset of the frames. No effect was found with
      different waveforms for the frame and the target. Results are related to recent
      findings indicating a similar effect in the azimuthal dimension. Possibly the
      effect is based on a mechanism in which the auditory system adapts to recently
      heard sound source positions.

PMID- 14674633
TI  - Vibrotactile localization on the arm: effects of place, space, and age.
AB  - Although tactile acuity has been explored for touch stimuli, vibrotactile
      resolution on the skin has not. In the present experiments, we explored the
      ability to localize vibrotactile stimuli on a linear array of tactors on the
      forearm. We examined the influence of a number of stimulus parameters, including
      the frequency of the vibratory stimulus, the locations of the stimulus sites on
      the body relative to specific body references or landmarks, the proximity among
      driven loci, and the age of the observer. Stimulus frequency and age group showed
      much less of an effect on localization than was expected. The position of
      stimulus sites relative to body landmarks and the separation among sites exerted
      the strongest influence on localization accuracy, and these effects could be
      mimicked by introducing an "artificial" referent into the tactile array.

PMID- 14674634
TI  - Configural face encoding and spatial frequency information.
AB  - Configural relations and a critical band of spatial frequencies (SFs) in the
      middle range are particularly important for face recognition. We report the
      results of four experiments in which the relationship between these two types of
      information was examined. In Experiments 1, 2A, and 2B, the face inversion effect
      (FIE) was used to probe configural face encoding. Recognition of upright and
      inverted faces and nonface objects was measured in four conditions: a no-filter
      condition and three SF conditions (low, medium, and high frequency). We found
      significant FIEs of comparable magnitudes for all frequency conditions. In
      Experiment 3, discrimination of faces on the basis of either configural or
      featural modifications was measured under the same four conditions. Although the
      ability to discriminate configural modifications was superior in the medium
      frequency condition, so was the ability to discriminate featural modifications.
      We conclude that the band of SF that is critical for face recognition does not
      contribute preferentially to configural encoding.

PMID- 14674635
TI  - Object-based connectedness facilitates matching.
AB  - In two matching tasks, participants had to match two images of object pairs.
      Image-based (IB) connectedness refers to connectedness between the objects in an
      image. Object-based (OB) connectedness refers to connectedness between the
      interpreted objects. In Experiment 1, a monocular depth cue (shadow) was used to
      distinguish different relation types between object pairs. Three relation types
      were created: IB/OB-connected objects, IB/OB-disconnected objects, and IB
      connected/OB-disconnected objects. It was found that IB/OB-connected objects were
      matched faster than IB/OB-disconnected objects. Objects that were IB-connected/OB
      disconnected were matched equally to IB/OB-disconnected objects. In Experiment 2,
      stereoscopic presentation was used. With relation types comparable to those in
      Experiment 1, it was again found that OB connectedness determined speed of
      matching, rather than IB connectedness. We conclude that matching of projections
      of three-dimensional objects depends more on OB connectedness than on IB
      connectedness.

PMID- 14674636
TI  - Object-based selection in the two-rectangles method is not an artifact of the
      three-sided directional cue.
AB  - A common means of investigating object-specific selection is the two-rectangles
      method, in which a target appears at one end of two rectangles (Egly, Driver, &
      Rafal, 1994). Prior to target presentation, one end of two parallel rectangles is
      cued by brightening the three line segments along one of its ends. When the
      target appears in the opposite end of the cued rectangle, responses tend to be
      faster and more accurate than when it appears in the end of the other rectangle,
      which is equally distant from the cue. This effect has been taken as evidence of
      object-specific selection of information. The present study rules out the concern
      that the object-specific effect that is found with this method is caused by the
      directional nature of the cue. That is, the three-sided cue, which essentially
      points to the "same-object" location, does not itself give rise to the object
      specific advantage. These results are discussed in terms of the combined roles of
      explicit object structure in the scene, past experience, and task set as
      contributing to the way in which information is organized and selected from a
      scene.

PMID- 14674637
TI  - Mirror-reflecting a picture of an object: what happens to the shape percept?
AB  - Although a two-dimensional picture never fully specifies the actual layout of the
      depicted three-dimensional scene, one is still able to make a three-dimensional
      interpretation. When a picture is mirror-reflected, the range of plausible scenes
      possibly corresponding with the depicted scene has not changed with respect to
      the original depiction. We were curious to find out whether the inherent picture
      ambiguities would be solved the same way or differently. Participants performed
      local attitude settings on three sets of pictures: (1) original pictures, (2)
      left-right mirrored pictures, and (3) up-down mirrored pictures. Pairwise
      comparison of the pictorial reliefs of the depicted object, reconstructed from
      the raw settings, revealed dissimilarities. The differences, however, could be
      drastically diminished by conducting an affine transformation correction taking
      into account not only the depths, but also the picture plane coordinates. The
      inherent ambiguities seemed thus to be solved differently between conditions. By
      factoring out different solutions to the ambiguities, the pictorial reliefs were
      found to be equivalent.

PMID- 14674638
TI  - Inhibition of return with rapid serial shifts of attention: implications for
      memory and visual search.
AB  - Horowitz and Wolfe (2001) suggested that inhibition of return (IOR) should not be
      observed in tasks that involve rapid deployments of attention. To examine this
      issue, five of six possible locations were sequentially cued with either short
      duration peripheral cues (50 msec) or long-duration peripheral cues (500 msec).
      As was expected, IOR was observed in the first two experiments at every cued
      location with the long-duration cues, with the magnitude of IOR decreasing for
      earlier cued locations relative to later cued locations. In the short-cue
      condition, IOR was observed at only one cued location (the second to last). The
      pattern of results for the short-duration cues was found regardless of whether
      the fixation cue was of a short (Experiment 1) or a long (Experiment 2) duration.
      In Experiment 3, the final fixation cue was removed, and IOR was again observed
      at virtually all locations in both the short- and the long-cue conditions. These
      findings indicate that IOR can be observed at multiple locations when attention
      is shifted rapidly between locations.

PMID- 14674639
TI  - A gradual spread of attention during mental curve tracing.
AB  - The visual system has to segregate objects that are relevant to behavior from
      other objects and the background, if they are embedded in a visual scene. This
      segregation process can be time consuming, especially if the relevant object is
      spatially extended and overlaps with other image components, but the cause of the
      delays is presently not well understood. In the present study, we used a curve
      tracing task to investigate processing delays during the grouping of contour
      segments into elongated curves. Our results indicate that contour segments that
      need to be grouped together are labeled with visual attention. Attention
      gradually spreads from contour segments that were labeled previously to other
      contours that are colinear and connected to them. The contour-grouping task is
      completed as soon as attention is directed to the entire curve. We conclude that
      processing delays during contour grouping are caused by a time-consuming spread
      of visual attention.

PMID- 14674640
TI  - Direct estimation of multidimensional perceptual distributions: assessing hue and
      form.
AB  - The procedures developed to assess the perceptual and decisional processes
      associated with detection in multidimensional space all require specialized
      statistical skills and analysis programs. The present article describes a
      regression model, designed to assess dimensional interactions, that is both
      computationally simpler and more accessible than those procedures. The
      papervalidates the regression model by comparing the perceptual space associated
      with the detection of hue and form mapped by the regression model with that
      mapped by Kadlec and Townsend's (1992a, 1992b) macro- and microanalyses. The
      results of both analyses showed that hue strongly influences the perception of
      form but that form only weakly influences the perception of hue. The parallel
      results of the two analyses suggest that the regression model is a valid
      alternative to multidimensional signal detection theory analysis.

PMID- 14674641
TI  - Comparison is not just subtraction: effects of time- and space-order on
      subjective stimulus difference.
AB  - In five experiments, participants made comparative judgments of paired successive
      or simultaneous stimuli. Time- or space-order errors were obtained, which varied
      with the interstimulus interval (ISI) or stimulus duration, as well as with the
      stimulus level. The results, in terms of scaled subjective differences, are well
      described by Hellstrom's (1979) sensation-weighting model. With successive
      presentation, in comparisons of line length and tone loudness, the first stimulus
      had the greater weight in determining the subjective difference for short ISIs,
      the second for longer ISIs. In comparisons of duration (auditory and visual), the
      second stimulus had the greater weight. For simultaneously presented line
      lengths, the left stimulus had the greater weight.

PMID- 14674642
TI  - Phase-shifting with computer-generated holograms written on a spatial light
      modulator.
AB  - We propose a new computer-controlled phase-shifting method based on computer
      generated holograms (CGHs) displayed on a spatial light modulator (SLM). In this
      method the accurate phase shifts required in phase-shifting digital holography or
      interferometry are induced by a suitable transformation of the encoding patterns
      of the CGH displayed on a SLM. Both the theoretical analysis and the experimental
      results demonstrate the feasibility of this approach. We also discuss possible
      applications of this method in the field of interferometric null testing of
      aspheres.

PMID- 14674643
TI  - Design of delay elements in a binary optical true-time-delay device that uses a
      White cell.
AB  - A White-cell-based binary optical true-time-delay device has two parts: the
      controller, or switching engine, and the delay elements. Here we discuss in
      detail the design of both glass blocks and lens trains as delay elements. Glass
      blocks can be used in our design for delays ranging from one to a few hundred
      picoseconds. Lens trains are suitable for longer delays. We also analyze the loss
      associated with each design and give design limits.

PMID- 14674644
TI  - Multireference binary phase-only filter optimized by regions of support.
AB  - A new formulation of a multiplex filter for filtering-based optical processors,
      based on the VanderLugt architecture, is presented. The multireference binary
      phase-only filter (MBPOF), optimized by regions of support (ROS), constitutes a
      formal rewriting of some multiplex or composite filters including optimization
      functions, such as the distribution function and the selection function. The
      first function optimizes the multiplexing of references into the multireference
      filter. The second function defines the ROS of an object's Fourier spectrum and
      can be independently used to optimize the conventional binary phase-only filter.
      Both functions result from a segmentation of the Fourier plane. The MBPOF with
      ROS can be optically implemented in a filtering-based optical processor owing to
      a binary-phase spatial light modulator. Simulation and optical results are given
      for different examples of the BPOF and the MBPOF, both with ROS optimizing
      different criteria of performance, such as peak-to-correlation energy,
      discrimination capability, and distortion sensitivity.

PMID- 14674645
TI  - Holographic characteristics of a 1-mm-thick photopolymer to be used in
      holographic memories.
AB  - Poly(vinyl alcohol-acrylamide) photopolymers are materials of interest in the
      field of digital information storage (holographic memories). We analyzed the
      behavior of a 1-mm-thick photopolymer. Using a standard holographic setup, we
      recorded unslanted diffraction gratings. The material has high angular
      selectivity (0.4 degrees), good sensitivity (88 mJ/cm2), and small losses caused
      by absorption and scattering of light. It also has a high maximum diffraction
      efficiency (70%). A significant induction period was seen in the material. The
      authors hypothesize that, during most of this induction period, polymerization
      does in fact take place but is not reflected in the appearance of the diffracted
      light until a certain threshold value of exposure is reached.

PMID- 14674646
TI  - Image-plane disk-type multiplex hologram.
AB  - We demonstrate, both theoretically and experimentally, that a disk-type multiplex
      hologram can be fabricated as an image-plane hologram that is suitable for white
      light line-source reconstruction. By adopting the method of direct object-image
      relationship, we build the theory based on the imaging property of lenses and on
      coordinate transformation. Numerical simulation shows the characteristics of this
      type of hologram. Experimental results reveal that the picket-fence effect that
      is encountered in the traditional multiplex hologram for images viewed at various
      distances has been eliminated. Using a reconstruction white-light line source of
      sufficient length, we observed an achromatic three-dimensional image.

PMID- 14674647
TI  - Efficient storage and transmission of ladar imagery.
AB  - We develop novel methods for compressing volumetric imagery that has been
      generated by single-platform (mobile) range sensors. We exploit the correlation
      structure inherent in multiple views in order to improve compression efficiency.
      We show that, for lossless compression, three-dimensional volumes compress more
      efficiently than two-dimensional (2D) images by a factor of 60%. Furthermore, our
      error metric for lossy compression suggests that accumulating more than nine
      range images in one volume before compression yields as much as a 99% improvement
      in compression performance over 2D compression.

PMID- 14674648
TI  - Three-dimensional image sensing and reconstruction with time-division multiplexed
      computational integral imaging.
AB  - A method to compute high-resolution three-dimensional images based on integral
      imaging is presented. A sequence of integral images (IIs) is captured by means of
      time-division multiplexing with a moving lenslet array technique. For the
      acquisition of each II, the location of the lenslet array is shifted periodically
      within the lenslet pitch in a plane perpendicular to the optical axis. The II
      sequence obtained by the detector array is processed digitally with
      superresolution reconstruction algorithms to obtain a reconstructed image,
      appropriate to a viewing direction, which has a spatial resolution beyond the
      optical limitation.

PMID- 14674649
TI  - Filling the Radon domain in computed tomography by local convex combination.
AB  - Radon data interpolation is a necessary procedure in computed tomography (CT),
      especially for reconstruction from divergent beam scanning. In a polar-grid
      representation, the Radon data of a fanbeam projection are populated on an arc,
      rather on a radial line. Collectively, the Radon data generated from a fanbeam CT
      system are unevenly populated: The population becomes sparser as the polar
      distance increases. In CT reconstruction, the Fourier central slice theorem
      requires a radial scanline full of Radon data. Therefore the vacant entries of a
      scanline must be filled by interpolation. In addition, interpolation is also
      required in polar-to-Cartesian conversion. In this paper we propose a practical
      interpolation technique for filling the vacant entries by local convex
      combination. It is a linear interpolant that generates a value for a grid point
      from the available data lying in its neighborhood, by a weighted average, with
      the weights corresponding to the inverse distances. In fact, the linear convex
      combination serves as a general flat-smoothing operation in filling a vacancy.
      Specifically, this technique realizes a variety of linear interpolations,
      including nearest-neighbor replication, two-point collinear, three-point
      triangulation, and four-point quadrilateral, and local extrapolation, in a
      unified framework. Algorithms and a simulation demonstration are provided.

PMID- 14674650
TI  - Talbot imaging and unification.
AB  - The fractional Talbot effect brings into play a superimposition of shifted and
      complex weightedreplicas of the original object. This phenomenon can be used to
      replicate images of nonperiodic objects by means of Talbot array illuminators.
      These diffractive elements can also be used to concentrate replicas into a single
      image. These techniques are useful for several applications such as beam shaping.

PMID- 14674651
TI  - Spatial-fringe-modulation-based quality map for phase unwrapping.
AB  - The quality-guided algorithm is a method widely used in phase unwrapping. The
      algorithm uses a quality map to guide its unwrapping process, and its validity
      depends on whether the quality map can truly reflect phase quality. In fringe
      projection surface profilometry, discontinuous surface structure, low surface
      reflectivity, and saturation of the image-recording system are sources of
      unreliable phase data. To facilitate the unwrapping process, we demonstrate an
      accurate quality map based on spatial fringe modulation, which is extracted from
      a single fringe pattern. Compared with temporal fringe modulation, the new
      criterion is more sensitive to spatial structure changes and less dependent on
      illumination conditions.

PMID- 14674652
TI  - Phase retrieval in digital speckle pattern interferometry by use of a smoothed
      space-frequency distribution.
AB  - We evaluate the use of a smoothed space-frequency distribution (SSFD) to retrieve
      optical phase maps in digital speckle pattern interferometry (DSPI). The
      performance of this method is tested by use of computer-simulated DSPI fringes.
      Phase gradients are found along a pixel path from a single DSPI image, and the
      phase map is finally determined by integration. This technique does not need the
      application of a phase unwrapping algorithm or the introduction of carrier
      fringes in the interferometer. It is shown that a Wigner-Ville distribution with
      a smoothing Gaussian kernel gives more-accurate results than methods based on the
      continuous wavelet transform. We also discuss the influence of filtering on
      smoothing of the DSPI fringes and some additional limitations that emerge when
      this technique is applied. The performance of the SSFD method for processing
      experimental data is then illustrated.

PMID- 14674653
TI  - Large optical nonlinearities of new organophosphorus fullerene derivatives.
AB  - Optical nonlinearities of five new organophosphorus fullerene derivatives with
      similar structures were determined by the Z-scan method by use of a nanosecond
      pulse laser at 532 nm. The experimental results demonstrate that the five
      derivatives have much larger excited-state absorption and nonlinear refraction
      than C60. The excited-state absorption cross sections are nearly two to three
      times that of C60. Using a five-level model to fit the experimental data, we
      obtained some parameters such as excited-state absorption and refraction cross
      sections. A simple analysis of correlations between molecular structure and
      nonlinear properties is given. Optical nonlinearities of the five new
      organophosphorus fullerene derivatives were compared with those of some other
      kinds of fullerene derivatives, and the results show that the nonlinearities of
      the new derivatives are the larger.

PMID- 14674654
TI  - Storage capacity of holo-interferograms.
AB  - The practical storage capacity of a holographic medium can be found by finely
      comparing reconstructions from independent holograms of an information-dense
      object wave. With the help of two orthogonally polarized reference waves, a pair
      of volume holograms is recorded simultaneously at imprint densities as high as
      4.1 x 10(10) bits/cm3. As a consequence of polarization, the holograms are not
      mutually coherent, and the twin encodings of the object wave can be reconstructed
      separately. These are brought into fine registration interferometrically and then
      scanned by a CCD camera. Experiments on glass-mounted Agfa 8E56, a fine-grained
      silver halide emulsion designed for holography, are reported. When the object
      wave was moderately dense in information, grain noise was the main cause of the
      reconstruction errors. Emulsional plasticity was the more significant factor both
      when the object wave was optically sparse and when it was extremely dense.
      Plasticity noise limited the information that could be retrieved to 2.7 x 10(10)
      bits/cm3, which is 2 orders of magnitude below the capacity suggested by the
      emulsion's bandwidth and grain-noise figures alone.

PMID- 14674655
TI  - Orthogonal aperture multiplexing for multilayered waveguide holographic read-only
      memories.
AB  - A multilayered waveguide holographic read-only memory is a promising candidate
      for the next generation of optical data storage systems. We improved the data
      density of the memory by using a multiplexing method with a set of orthogonal
      optical masks. We multiplexed as many as nine images into one waveguide hologram,
      and all the observed images had negligible cross talk. This made it possible to
      achieve a ninefold increase in data density. We provide experimental results for
      both metallic and liquid-crystal masks.

PMID- 14674656
TI  - Long-term outcome of unruptured cerebral aneurysms.
AB  - BACKGROUND: The frequency at which unruptured cerebral aneurysms are detected has
      increased due to advances in low- or non-invasive diagnostic techniques. Despite
      the recent improvements in surgical and medical management of aneurysmal
      subarachnoid hemorrhages, however, the overall case-fatality rate of this disease
      is still high. To reduce it, the natural history of unruptured cerebral aneurysms
      should be better understood. METHODS: The subjects consisted of 156 patients with
      unruptured cerebral aneurysms who had been admitted to the Department of Surgical
      Neurology, Jichi Medical School Hospital or Jichi Medical School Ohmiya Medical
      Center, Japan, between January 1989 and December 1998. All of the patients were
      classified according to the process by which aneurysms had been detected. The
      expected number of deaths was calculated by using age- and sex-specific mortality
      rates obtained from the vital statistics. A standardized mortality ratio and 95%
      confidence interval were calculated by using the expected and observed numbers of
      deaths. RESULTS: The standardized mortality ratios differed among the groups
      according to the process of detecting aneurysms. The incidence rate of rupture of
      unruptured cerebral aneurysms was 1.3 per 100 person-years. The annual rupture
      rate of unruptured cerebral aneurysms was higher than previously reported. The
      survival rate of the group that underwent surgical treatment for unruptured
      cerebral aneurysms was higher than that of the untreated group. CONCLUSIONS: The
      annual rupture rate of unruptured cerebral aneurysms may be higher than
      previously reported.

PMID- 14674657
TI  - Smoking patterns of university woman students in Miyagi, Japan: the Miyagaku
      Study.
AB  - BACKGROUND: The increase in the smoking rate among young women is a worldwide
      problem. However, few reports have focused on female students, in particular,
      with detailed accounts of their smoking behavior. The aim of this study was to
      clarify the smoking patterns of Japanese women of approximately 20 years of age.
      METHODS: Smoking behavior, age at initiation, favorite brand and related
      attitudes were examined using a cross-sectional anonymous questionnaire
      administered to students at a women's university in Miyagi, Japan in 2000.
      RESULTS: Of 2,984 subjects (response rate: 96%), 16% said that they smoke (95%
      confidence interval 15-18%): 7% of freshmen, 16% of sophomores, 22% of juniors
      and 20% of seniors. While music majors were most likely to smoke (21%), domestic
      science majors had the lowest rate of smoking (10%). Among the smokers, 27%
      started the habit at age 20 years, the legal age in Japan, and 25% started at age
      18. The favorite brand was Marlboro (39%), followed by Mild Seven (16%), a
      domestic brand. One-third of the smokers had no plans to quit. CONCLUSIONS:
      Reaching the legal age and entering university may prompt young women to start
      smoking habitually. In contrast to its overall market share in Japan, a US brand
      is now favored by current young female smokers.

PMID- 14674658
TI  - Personality as assessed by egogram is a possible independent predictive variable
      for post-discharge smoking abstinence in male cancer patients.
AB  - BACKGROUND: Little is known about the relationship between a patient's
      personality and smoking behavior. METHODS: We assessed the smoking status of 262
      male smokers who had been diagnosed with cancer and admitted to a teaching
      hospital, using a self-administered questionnaire that was mailed to the patients
      6 months after discharge. The personality of the patients was assessed with the
      Kyushu University Egogram at admission, and the patients were categorized into
      five groups according to the ego state with the highest value among the five ego
      states, namely "Critical Parent" dominant, "Nurturing Parent" dominant, "Adult"
      dominant, "Free Child" dominant and "Adapted Child" dominant. Multivariate
      logistic regression analyses were used to assess the influence of the type of
      personality on smoking behavior after hospital discharge with adjustment for
      considerable predictive variables. RESULTS: The smoking cessation rate at 6
      months after hospital discharge was 63% (164/262). Multivariate analyses revealed
      that after adjustment for age, cancer site, length of hospital stay, time elapsed
      since last cigarette, self-confidence to quit smoking and strength of nicotine
      dependence, and being an Adult dominant personality were positively (p<0.01), and
      being a Free Child dominant personality was negatively (p<0.05) associated with
      post-discharge abstinence. These findings did not change when the non-responders
      (n=50) of the questionnaire were included in the analysis as post-discharge
      smokers. CONCLUSIONS: These findings indicate that a male cancer patient's
      personality as assessed by the egogram has predictive significance for whether
      the patient will have a smoking habit after discharge.

PMID- 14674659
TI  - Effects of particulate matter on daily mortality in 13 Japanese cities.
AB  - BACKGROUND: In recent years, numerous reports demonstrating the relationship
      between an increase in the concentration of fine particulate matter (PM2.5) and
      daily mortality have been released in the United States and Europe. There have
      been few studies that clearly characterize the short-term effects of particulate
      matter on the mortality in Japan. We conducted data analysis to investigate the
      short-term effects of suspended particulate matter (SPM) on mortality in Japan.
      METHODS: In this study, we used data sets from the 13 largest cities containing
      data on the daily mortality of residents aged 65 years or older, concentrations
      of air pollutants including SPM, temperature, and humidity. Risk ratios for
      mortality resulting from respiratory diseases, cardiovascular diseases, and all
      causes other than accidents, from 1990 through 1994, were summarized using a
      generalized additive model (GAM) and a meta-analysis of random effect model.
      RESULTS: The risk ratios for an increase of 10 microg/m3 in SPM concentrations
      adjusted for SO2, NO2, CO, Ox, temperature, and humidity were 1.0077 for all
      causes of mortality, 1.0109 for respiratory diseases, and 1.0091 for
      cardiovascular diseases, and the lower limits of the 95% confidence intervals for
      the risk ratios were greater than one for all cases. With regards to the effects
      of time lag, risk ratios were higher for the SPM concentrations on the day when
      the mortality was recorded, and the preceding day. CONCLUSIONS: These results
      suggest a positive relationship between SPM concentrations and daily mortality in
      Japan.

PMID- 14674660
TI  - Smoking and colorectal cancer in a non-Western population: a prospective cohort
      study in Japan.
AB  - BACKGROUND: The risk of colorectal cancer in relation to smoking habits has been
      examined mostly in Caucasians, and evidence for other ethnic groups is still
      scarce. METHODS: Our data came from the Japan Collaborative Cohort (JACC) Study.
      From 1988 through 1990, 25,260 men and 34,619 women aged 40-79 years completed a
      questionnaire on cigarette smoking and other lifestyle factors. Hazard ratios
      (HR) were estimated by fitting proportional hazards models. RESULTS: During the
      mean follow-up of 7.6 years through December 1997, we documented 408 incident
      colon cancers and 204 rectal cancers. We found a non-significant increase in
      colon cancer risk in male current smokers compared with never smokers. The
      multivariate-adjusted hazard ratios were 1.07 (95% confidence interval [CI]: 0.72
      1.59) for ex-smokers and 1.23 (95% CI: 0.85-1.78) for current smokers. We however
      failed to observe a clear dose-response relationship between smoking intensity or
      duration and colon cancer risk. The adjusted hazard ratio was 1.07 (95% CI: 0.71
      1.61) even for 40+ years of smoking. Almost no increase in colon cancer risk was
      detected for female smokers, and male smokers were not at an enhanced risk of
      rectal cancer. CONCLUSIONS: Cigarette smoking was not a strong risk factor for
      colorectal cancer even after a long-term exposure, although a weak association
      remains open to discussion.

PMID- 14674661
TI  - Reference birth weight, length, chest circumference, and head circumference by
      gestational age in Japanese twins.
AB  - BACKGROUND: Numerous birth weight standards for twins have been reported in
      western countries, whereas little is in Japan. The aim of this study is to
      present birth weight, birth length, chest circumference, and head circumference
      references, clarifying features related to these body size parameters, and to
      compare our birth weight references with recent report of birth weight norms of
      Japanese twins using the vital statistics. METHODS: The subjects consisted of
      1,061 twin pairs in total, with birth years ranging from 1968 through 1990. Data
      was obtained from the Twins Protocol Questionnaire, which asked for information
      about twins' growth and development in infancy, and the "Maternal and Child
      Health Handbook," which was presented by Ministry of Health and Welfare.
      Statistical means, standard deviations, and selected percentiles by gestational
      age were calculated and smoothed using data that contained at least gestational
      age and one of the four items. RESULTS: Birth weight was significantly lighter
      than that of singletons when three additional parameters, especially chest and
      head circumference, were not measured. Gestational age was correlated with
      weight, length, chest circumference, and head circumference, in that order, for
      both sexes. Compared with singletons, birth weight difference in twins was marked
      and slight difference was observed as to length, whereas no difference was
      observed as to chest and head circumference. The present results as to birth
      weight were consistently similar to the birth weight norms of twins using vital
      statistics in Japan. CONCLUSION: Growth standards for twins, especially as to
      birth weight, are essential to understand and evaluate intrauterine growth of
      twins.

PMID- 14674662
TI  - CARD 15 and toll-like receptors: the link with Crohn's disease.

PMID- 14674663
TI  - From microenteropathy to villous atrophy: what is treatable?

PMID- 14674664
TI  - Hepatitis C virus: simply too smart to be just a liver pathogen.

PMID- 14674665
TI  - Comparable Helicobacter pylori eradication rates obtained with 4- and 7-day
      rabeprazole-based triple therapy: a preliminary study.
AB  - BACKGROUND: Rabeprazole is a new proton pump inhibitor, which has been reported
      to induce a faster acid suppression than other drugs of the same category. This
      might be useful to reduce the duration of anti-Helicobacter therapies. AIMS: The
      aim of this study was to assess whether there is the possibility of shortening a
      rabeprazole-based triple therapy from 7 to 4 days without compromising its
      efficacy in the eradication of Helicobacter pylori infection. PATIENTS: A total
      of 128 consecutive dyspeptic patients with H. pylori infection were recruited for
      this controlled, randomized, open and parallel-group trial comparing the efficacy
      of two durations of the same rabeprazole-based triple therapy. METHODS: All
      patients were subdivided to receive a combination of rabeprazole 20 mg twice
      daily, clarithromycin 250 mg twice daily and metronidazole 500 mg twice daily
      (RCM) for 4 days (n = 63) and for 7 days (n = 65). At baseline, they underwent
      breath 13C-urea test and endoscopy with biopsies for rapid urease testing and
      histology to confirm infection with H. pylori. Eradication was determined by a
      negative 13C-urea breath test within 28-32 days after the end of therapy.
      RESULTS: Overall eradication rates were similar for patients treated with the 4-
      and the 7-day periods (intention-to-treat and per-protocol analyses showed a
      success rate of 81% versus 78% and 88% versus 85%, respectively; P = NS).
      Tolerance was similar in both groups. Most adverse events were mild to moderate,
      and only two patients were withdrawn because of them. CONCLUSIONS: The
      eradication rate of the 4-day regimen was equivalent to that of the same 7-day
      regimen based on rabeprazole plus clarithromycin and metronidazole. Therefore,
      the 4-day regimen of RCM seems to give us the possibility of adopting a shorter
      than-usual duration of therapy against H. pylori.

PMID- 14674666
TI  - Gluten sensitivity and 'normal' histology: is the intestinal mucosa really
      normal?
AB  - BACKGROUND: Early pathogenetic events of gluten intolerance may be overlooked in
      patients with serologic markers of celiac disease and normal intestinal mucosa by
      both conventional histology and immunohistochemistry. AIMS: To investigate if a
      submicroscopical damage of the absorptive cell surface was associated with
      developing gluten sensitivity. PATIENTS AND METHODS: Duodenal biopsies of seven
      subjects with positive anti-endomysial antibodies and normal histology underwent
      ultrastructural evaluation of the epithelial surface by means of both scanning
      and transmission electron microscopy. Specimens of intestinal mucosa of 14
      children with non-celiac conditions were used as controls. RESULTS: In four
      patients, electron microscopy revealed alterations of the enterocyte brush border
      with a significant reduction of the height of microvilli. After several months,
      three of them had a second biopsy that eventually showed histological
      modifications suggestive of celiac disease. In the other three patients, no
      significant alteration of enterocyte ultrastructure was observed. One of them,
      rebiopsied after 12 months, still showed a normal duodenal histology.
      CONCLUSIONS: Gluten sensitivity can be associated with 'minimal' mucosal changes
      not detectable with conventional light microscopy. Such lesions, which primarily
      involve microvillous structure, may imply a reduction of intestinal absorptive
      surface already in the latent stage of the disease.

PMID- 14674667
TI  - Factor analysis of bowel symptoms in US and Italian populations.
AB  - BACKGROUND AND AIMS: Functional gastrointestinal disorders are diagnosed by the
      presence of a characteristic set of symptoms. Aims of this study were to validate
      the Rome symptom criteria by factor analysis and to determine whether symptoms
      cluster in the same way in different cultures. METHODS: One thousand forty-one
      gastroenterology clinic patients in the US (response rate 53%) and 228 family
      members accompanying clinic patients in Italy (84%) completed a previously
      validated symptom questionnaire. Factor analysis identified clusters of symptoms
      which are highly correlated with each other, and these were compared to the Rome
      diagnostic criteria. RESULTS: In the US, 13 factors were identified. The
      irritable bowel factor was composed of three core symptoms corresponding to the
      Rome II classification system. Two dyspepsia factors were identified which
      correspond to the ulcer- and motility-like subtypes proposed in the Rome I
      classification system. All symptoms of constipation formed a single cluster as
      proposed in the Rome II classification system. Symptom clusters in the US agreed
      well with symptom clusters identified in Italian subjects. CONCLUSIONS:
      Empirically derived symptom clusters agree in most respects with the Rome II
      classification system and support their validity. These symptom clusters are
      independent of cultural differences in diet and behaviour.

PMID- 14674668
TI  - Role of small bowel investigation in iron deficiency anaemia after negative
      endoscopic/histologic evaluation of the upper and lower gastrointestinal tract.
AB  - BACKGROUND: The usefulness of small bowel investigation in iron deficiency
      anaemia (IDA) patients is controversial. AIM: To evaluate the presence of small
      bowel lesions likely to cause IDA in patients with unexplained IDA after negative
      gastroscopy with biopsies and colonoscopy (CS). METHODS: A total of 117
      outpatients, referred for unexplained IDA, underwent gastroscopy with biopsies
      and colonscopy. In 17 (14.5%) patients, endoscopic/histological investigations
      were negative. Of these patients, 13 underwent small bowel follow-through (SBFT)
      and if necessary to confirm the diagnosis, further gastrointestinal (GI)
      investigations. RESULTS: Small bowel lesions likely to cause IDA were found in
      five (38%) patients. Four of these lesions were detected by SBFT, two of them
      were malignant. These findings, confirmed at surgery and ileoscopy (IS), led to
      the final diagnoses ofjejunal and ileal adenocarcinoma, idiopathic ileal ulcers
      and ileal Crohn's disease. In one case, after negative SBFT, jejunal
      angiodysplasia was detected by video capsule endoscopy (VCE). Faecal occult blood
      test (FOBT) was positive in four (31%) patients, all of whom presented lesions
      likely to cause IDA, detected in three cases by SBFT and in one case by VCE.
      CONCLUSIONS: This study shows the importance of investigating the small bowel in
      IDA patients after negative upper and lower GI endoscopy, particularly if FOBT is
      positive.

PMID- 14674669
TI  - Molecular analysis of V(H)I+ B lymphocytes in hepatitis C patients.
AB  - BACKGROUND AND AIMS: Hepatitis C virus infection is often associated with
      lymphoproliferative disorders such as essential mixed cryoglobulinemia and B-cell
      non-Hodgkin lymphoma, which show preferential expression of VHI family products.
      By analyzing immunoglobulin heavy chain usage, we addressed the question of
      whether or not clonal B-cell expansion occurrs in patients free of essential
      mixed cryoglobulinemia or non-Hodgkin lymphoma. PATIENTS AND METHODS: Four
      hepatitis C virus-positive patients, all undergoing liver transplantation, were
      studied. Peripheral blood, intra-hepatic, and lymph node lymphocytes were used as
      a source of B cells. A patient with hepatocellular carcinoma and fresh blood from
      four healthy donors were used as negative controls. VHI family sequences were
      cloned and analyzed by reverse transcription-polymerase chain reaction. RESULTS:
      Immunoglobulin heavy chain sequences from clonally expanded B lymphocytes were
      identified in three out of four hepatitis C virus-infected patients. The clonally
      expanded B lymphocyte populations showed a broad spectra of immunoglobulin heavy
      chain gene usage. CONCLUSIONS: HCV infection can induce B-cell expansion with
      larger clonal variation. The restricted V gene usage in hepatitis C virus
      associated non-Hodgkin lymphoma suggests that there may be selection mechanisms
      to develop non-Hodgkin lymphoma from non-malignant, clonally expanded B-cell
      populations in hepatitis C virus-infected patients.

PMID- 14674670
TI  - Integration of hepatitis B virus containing mutations in the core promoter/X gene
      in patients with hepatocellular carcinoma.
AB  - Integration of hepatitis B virus is thought to be an essential step in hepatitis
      B virus associated hepatocarcinogenesis. Mutations at nucleotides 1762 and 1764
      in the hepatitis B virus, within a sequence encoding both the core promoter gene
      and the X gene, have been found frequently in patients with hepatocellular
      carcinoma. However, integration of these mutant sequences has not been reported
      to date. METHODS: A 228-base pair segment of the hepatitis B virus core promoter
      gene was amplified from hepatocellular carcinomas and adjacent non-tumourous
      liver tissue by nested PCR and sequenced. Integration of hepatitis B virus into
      human genomic DNA was investigated using the 'genome walking' method. RESULTS:
      Point mutations were found in both hepatitis B virus nucleotides 1762 and 1764 in
      8 of 14 hepatocellular carcinoma tissues (57%) and in 11 of 14 adjacent non
      tumourous liver tissues (79%). Three patients were evaluated using the 'genome
      walking' method; all were found to have hepatitis B virus DNA integrated in their
      hepatocellular carcinoma (two patients) and/or in their non-tumourous liver
      tissue (three patients). Integration occurred in all tissues near host genomic
      sites that are prone to integration. Hepatitis B virus was integrated at or near
      the hepatitis B virus DR1 site in all samples, and all contained truncated X gene
      sequences that have been reported to be capable of producing fusion transcripts
      with transactivation potential. CONCLUSIONS: Integrated hepatitis B virus DNA
      containing core promoter mutations at nucleotides 1762 and 1764 was found in
      hepatocellular carcinoma and/or adjacent non-tumourous liver tissue of three
      patients. These findings leave open the possibility that insertional mutagenesis
      or transactivation by fusion transcripts resulting from hepatitis B virus
      integration could play a role in hepatocarcinogenesis in some patients.

PMID- 14674671
TI  - Association between the primary biliary cirrhosis specific anti-sp100 antibodies
      and recurrent urinary tract infection.
AB  - BACKGROUND AND AIMS: Recurrent urinary tract infections (rUTI) have been
      suggested to be involved in the induction of anti-mitochondrial antibodies (AMA),
      the serological hallmark of primary biliary cirrhosis (PBC), in view of the
      presence of AMA in rUTI women without liver disease and conversely of a high
      prevalence of rUTI in women with PBC. This prompted us to investigate whether PBC
      specific anti-nuclear antibodies (ANA) to sp100, gp210 and lamin B receptor (LBR)
      antigens may also be related to rUTI. METHODS AND SUBJECTS: PBC-specific ANA
      reactivities were investigated in 20 women with rUTI but without liver disease,
      some of whom were AMA-seropositive; 40 women with PBC, with or without rUTI; and
      104 pathological and 23 healthy controls. RESULTS: Among the women with rUTI but
      without liver disease, 8 (80%) of 10 AMA-positive women reacted with sp100
      compared with none of the 10 AMA-negative women. Among the PBC patients, 14 (74%)
      of 19 with rUTI and 1 (4.8%) of the 21 without rUTI reacted with sp100. None of
      the rUTI women without liver disease reacted with gp210 or LBR. None of 127
      pathological and healthy controls had PBC-specific ANA reactivity. CONCLUSIONS:
      Anti-sp100 reactivity strongly correlates with AMA seropositivity in rUTI women,
      with or without evidence of primary biliary cirrhosis. These findings provide
      additional support to the notion that E. coli infection is involved in the
      induction of PBC-specific autoimmunity. Additional factors must be involved in
      the progression to overt autoimmune disease.

PMID- 14674672
TI  - Long-term outcome of argon plasma coagulation therapy for bleeding caused by
      chronic radiation proctopathy.
AB  - BACKGROUND: Radiation-induced proctopathy is a serious complication of radiation
      therapy for pelvic malignancy. AIM: To assess the safety and efficacy of argon
      plasma coagulation in the treatment of haemorrhagic radiation-induced
      proctopathy. PATIENTS: Twenty-four patients with rectal bleeding due to radiation
      induced proctopathy were prospectively enrolled in the study. METHODS:
      Indications for treatment were iron deficiency anaemia (n = 16) and persistent
      bleeding, despite pharmacotherapy (n = 8). Argon flow and power used were 0.8-1.2
      l/min and 40 W, respectively. An interval of at least 4 weeks was allowed between
      treatment sessions. Haemoglobin level, bleeding severity score, number of
      admissions and transfusion requirements were recorded after endoscopic
      coagulation and before 12 and 24 months. RESULTS: A median of 2.5 therapeutic
      sessions per patient were performed (range 1-6). All patients reported clinical
      improvement and/or cessation of rectal bleeding. The mean value of the bleeding
      severity score decreased from 2.9 to 0.8 (P < 0.01), while average haemoglobin
      levels increased by a mean of 1.9 mg/dl at the end of the treatments (P < 0.05).
      During a minimum follow-up of 24 months (range 24-60), rectal bleeding recurred
      in two cases and was successfully retreated endoscopically. One patient developed
      a recto-vaginal fistula. CONCLUSIONS: Argon plasma coagulation appears to be a
      safe and effective technique for management of rectal bleeding caused by
      radiation-induced proctopathy.

PMID- 14674673
TI  - An unusual endoscopic finding: Trichuris trichiura. Case report and review of the
      literature.
AB  - Detection of Trichuris trichiura during colonoscopic examination is an unusual
      finding, at least in developed countries. We report a case of a coincidental
      endoscopic diagnosis of whipworm infestation performed in a patient referred to
      our open-access endoscopy even before a faecal examination for ova and/or
      parasites had been performed. Review of literature on colonoscopic diagnosis of
      T. trichuria is provided.

PMID- 14674674
TI  - Infliximab-induced lupus in Crohn's disease: a case report.
AB  - An 18-year-old male patient was under treatment with infliximab at a dose of 5
      mg/kg at Weeks 0, 2 and 6 for refractory Crohn's disease. In June 2002, the
      patient was admitted to the Outpatient Clinic of the Rheumatology Unit for
      arthralgia affecting the small joints, non-pruritic crops of purple skin lesions
      and malar rash in the face. Serum antinuclear antibodies were positive (1:640
      speckled pattern), and anti-double-stranded DNA was positive (1:80); moreover,
      positivity of anti-extractable nuclear antigen was observed. Antihistone
      antibodies, lupus anticoagulant and anticardiolipin antibodies were negative. A
      diagnosis of infliximab-induced lupus was made and the drug treatment was
      withdrawn. However, 3 months after withdrawal of treatment, the patient still
      showed clinical and laboratory symptoms of systemic lupus erythematosus. After 6
      months of treatment, systemic lupus erythematosus-related symptoms disappeared
      and anti-double-stranded DNA returned to normal. The patient is currently under
      treatment with prednisone 20 mg/day for systemic lupus erythematosus and with
      oral mesalazine 2.4 mg/day for Crohn's disease. Treatment with infliximab is
      known to produce an increase of autoantibodies (antinuclear antibodies, anti
      double-stranded DNA), but not clinical disease. This is the first case, to our
      knowledge, of onset of prolonged infliximab-induced lupus.

PMID- 14674675
TI  - Endoscopic treatment of gastro-oesophageal reflux disease (GORD): a systematic
      review.
AB  - Gastro-oesophageal reflux disease represents an extremely common disorder which
      has a substantial impact on patients' quality of life and use of health care
      resources. Gastro-oesophageal reflux disease is a chronic relapsing disease for
      which a lifelong solution is needed. Until now the two competing therapeutic
      modalities have been the medical and surgical therapies. Quite recently a third
      option has become available. A number of endoscopic anti-reflux procedures have
      been described, with the common goal of creating an anti-reflux barrier, thus
      obviating long-term proton pump inhibitors and the cost and potential risk of
      laparoscopic Nissen fundoplication. In this review the different techniques are
      thoroughly examined and the results are critically evaluated, giving special
      emphasis to efficacy, safety and durability of these new anti-reflux procedures.
      Available data show that these anti-reflux techniques produce significant
      improvement in gastro-oesophageal reflux disease symptomatology and quality of
      life as well as reduce the use of anti-reflux medication, without causing serious
      morbidity or mortality. However, the majority of these techniques have failed to
      adequately control oesophageal acid reflux. Endoscopic anti-reflux therapies
      therefore sound very attractive-being less invasive than surgery-and show a
      significant promise, but are still in the early stages of assessment. Large-scale
      randomized multi-centre trials comparing control groups with sham procedures are
      essential to confirm their efficacy. Further studies are also necessary to
      determine what modifications these techniques require in order to produce maximum
      clinical efficacy and durability. However, considering that current therapies
      (both medical and surgical) of gastro-oesophageal reflux disease are highly
      effective, the need for such new endoscopic modalities may be questionable.
      Moreover, appropriate trials in dedicated centres should be carried out to assure
      that the enthusiasm commonly associated with new technology is justified and can
      be generalized to open-access endoscopists.

PMID- 14674676
TI  - Detection of genomic Helicobacter pylori DNA in the blood of patients positive
      for the infection.

PMID- 14674677
TI  - Characterization of the inhibitory effects of erythromycin and clarithromycin on
      the HERG potassium channel.
AB  - Both erythromycin and clarithromycin have been reported to cause QT prolongation
      and the cardiac arrhythmia torsade de pointes in humans, however direct evidence
      documenting that these drugs produce this effect by blocking human cardiac ion
      channels is lacking. The goal of this study was to test the hypothesis that these
      macrolide antibiotics significantly block the delayed rectifier current (IKr)
      encoded by HERG (the human ether-a-go-go-related gene) at drug concentrations,
      temperature and ionic conditions mimicking those occurring in human subjects.
      Potassium currents in HEK 293 cells stably transfected with HERG were recorded
      using a whole cell voltage clamp method. Exposure of cells to erythromycin
      reduced the HERG encoded potassium current in a concentration dependent manner
      with an IC50 of 38.9 +/- 1.2 microM and Hill Slope factor of 0.4 +/- 0.1.
      Clarithromycin produced a similar concentration-dependent block with an IC50 of
      45.7 +/- 1.1 microM and Hill Slope factor of 1.0 +/- 0.1. Erythromycin (25-250
      microM) and clarithromycin (5 or 25 microM) also produced a significant decrease
      in the integral of the current evoked by an action potential shaped voltage clamp
      protocol. The results of this study document that both erythromycin and
      clarithromycin significantly inhibit the HERG potassium current at clinically
      relevant concentrations.

PMID- 14674678
TI  - Structure and Ca2+ regulation of frog photoreceptor guanylate cyclase, ROS-GC1.
AB  - Rod outer segment membrane guanylate cyclase (ROS-GC) is a critical component of
      the vertebrate phototransduction machinery. In response to photoillumination, it
      senses a decline in free Ca(2+) levels from 500 to below 100 nM, becomes
      activated, and replenishes the depleted cyclic GMP pool to restore the dark state
      of the photoreceptor cell. It exists in two forms, ROS-GC1 and ROS-GC2. In outer
      segments, ROS-GCs sense fluctuations in Ca(2+) via two Ca(2+)-binding proteins,
      which have been termed GCAP1 and GCAP2. In the present study we report on the
      cloning of two ROS-GCs from the frog retinal cDNA library. These cyclases are the
      structural and functional counterparts of the mammalian ROS-GC1 and ROS-GC2.
      There is, however, an important difference between the regulation of mammalian
      and frog ROS-GC1: In contrast to the mammalian, the frog form does not require
      the myristoylated form of GCAP1 for its Ca(2+)-dependent modulation. This feature
      is not dependent upon the ability of frog GCAP1 to bind Ca(2+) because
      unmyristoylated GCAP1 mutants which do not bind Ca(2+), activate frog ROS-GC1.
      The findings establish frog as a suitable phototransduction model and show a
      facet of frog ROS-GC signaling, which is not shared by the mammalian form.

PMID- 14674679
TI  - Gene expression profile of butyrate-inhibited vascular smooth muscle cell
      proliferation.
AB  - Excessive proliferation of vascular smooth muscle cells (VSMCs) is a critical
      element in the development of several vascular pathologies, particularly in
      atherosclerosis and in restenosis due to angioplasty. We have shown that
      butyrate, a powerful antiproliferative agent, a strong promoter of cell
      differentiation and an inducer of apoptosis inhibits VSMC proliferation at
      physiological concentrations with no cytotoxicity. In the present study, we have
      used cDNA array technology to unravel the molecular basis of the
      antiproliferative effect of butyrate on VSMCs. To assess the involvement of gene
      expression in butyrate-inhibited VSMC proliferation, proliferating VSMCs were
      exposed to 5 mmol/l butyrate 1 through 5 days after plating. Expression profiles
      of 1.176 genes representing different functional classes in untreated control and
      butyrate treated VSMCs were compared. A total of 111 genes exhibiting moderate
      (2.0-5.0 fold) to strong (> 5.0 fold) differential expression were identified.
      Analysis of these genes indicates that butyrate treatment mainly alters the
      expression of four different functional classes of genes, which include: 43 genes
      implicated in cell growth and differentiation, 13 genes related to stress
      response, 11 genes associated with vascular function and 8 genes normally present
      in neuronal cells. Examination of differentially expressed cell growth and
      differentiation related genes indicate that butyrate-inhibited VSMC proliferation
      appears to involve down-regulation of genes that encode several positive
      regulators of cell growth and up-regulation of some negative regulators of growth
      or differentiation inducers. Some of the down-regulated genes include
      proliferating cell nuclear antigen (PCNA), retinoblastoma susceptibility related
      protein p130 (pRb), cell division control protein 2 homolog (cdc2), cyclin B1,
      cell division control protein 20 homolog (p55cdc), high mobility group (HMG) 1
      and 2 and several others. Whereas the up-regulated genes include cyclin D1,
      p21WAF1, p141NK4B/p15INK5B, Clusterin, inhibitor of DNA binding 1 (ID1) and
      others. On the other hand, butyrate-responsive stress-related genes include some
      of the members of heat shock protein (HSP), glutathione-s-transferase (GST),
      glutathione peroxidase (GSH-PXs) and cytochrome P450 (CYP) families.
      Additionally, several genes related to vascular and neuronal function are also
      responsive to butyrate treatment. Although involvement of genes that encode
      stress response, vascular and neuronal functional proteins in cell proliferation
      is not clear, cDNA expression array data appear to suggest that they may play a
      role in the regulation of cell proliferation. However, cDNA expression profiles
      indicate that butyrate-inhibited VSMC proliferation involves combined action of a
      proportionally large number of both positive and negative regulators of growth,
      which ultimately causes growth arrest of VSMCs. Furthermore, these butyrate
      induced differential gene expression changes are not only consistent with the
      antiproliferative effect of butyrate but are also in agreement with the roles
      that these gene products play in cell proliferation.

PMID- 14674680
TI  - Effect of pentoxifylline on arachidonic acid metabolism, neutral lipid synthesis
      and accumulation during induction of the lipocyte phenotype by retinol in murine
      hepatic stellate cell.
AB  - In liver fibrosis, the quiescent hepatic stellate cells (HSC) are activated to
      proliferate and express the activated myofibroblast phenotype, losing fat
      droplets and the stored vitamin A, and depositing more extracellular matrix.
      Therapeutic strategies for liver fibrosis are focused on HSC. Pentoxifylline
      (PTF), an analog of the methylxanthine, prevents the biochemical and histological
      changes associated with animal liver fibrosis. The aim of the present study was
      to investigate the phenotypic change of myofibroblasts into quiescent lipocytes
      by PTF and/or retinol, using a permanent cell line GRX that represents murine
      HSC. We studied the action of both drugs on the synthesis of neutral lipids,
      activity of phospholipase A2 (PLA2), release of arachidonic acid (AA) and
      prostaglandins synthesis. Accumulation and synthesis of neutral lipids was
      dependent upon association of retinol with PTF. PTF (0.5 mg/mL) alone did not
      induce lipid accumulation and synthesis, but in cells induced by physiologic
      concentration of retinol (1-2.5 microM), it increased the quantity of stored
      lipids. Retinol and PTF (5 microM and 0.1 mg/mL, respectively) had a synergistic
      effect on neutral lipid synthesis and accumulation. In higher PTF concentrations
      (0.5 and 0.7 mg/ml), the synthesis was stimulated but accumulation decreased.
      Membrane-associated PLA2 activity decreased after PTF treatment, which increased
      the AA release 8 fold, and significantly increased the production of PGE2, but
      not of PGF2. However, when in presence of retinol, we observed a slightly higher
      increase in PGE2 and PGF2a production. In conclusion, PTF treatment generated an
      excess of free AA. We propose that retinol counteracts the action of PTF on the
      AA release and PGs production, even though both drugs stimulated the lipocyte
      induction in the HSC.

PMID- 14674681
TI  - Thioredoxin restores nitric oxide-induced inhibition of protein kinase C activity
      in lung endothelial cells.
AB  - We previously reported that exposure to exogenous nitric oxide (NO) causes
      diminished expression of thioredoxin/thioredoxin reductase, a critical component
      of the redox system that regulates the functions of redox-sensitive enzymes,
      receptors, and transcription factors. Here we examined the role of thioredoxin in
      NO-induced inhibition of protein kinase C (PKC) isoform(s) and potential
      interaction of PKC and thioredoxin in pulmonary artery endothelial cells (PAEC)
      in culture. Exposure to NO gas (8 ppm) significantly diminished the catalytic
      activity of the representative isoforms of the conventional, novel, and atypical
      PKCs alpha, epsilon, and zeta, respectively, in PAEC. Further examination of NO's
      effect on PKC-zeta revealed that NO-induced inhibition of the catalytic activity
      of PKC-zeta was time-dependent and regulated by a posttranscriptional mechanism.
      NO-induced loss of the catalytic activity of PKC-zeta was restored by incubation
      with the disulfide reducing agent dithiothreitol (DTT) as well as by purified
      thioredoxin or thioredoxin reductase. Confocal imaging studies revealed co
      localization of PKC and thioredoxin in PAEC. These results indicate that: (1) NO
      induced inhibition of PKC isoforms is associated with S-nitrosylation-mediated
      disulfide formation of active site thiols in PKC-zeta as the disulfide reducing
      agent DTT and/or the thioredoxin enzyme system restore PKC-zeta catalytic
      activity and (2) NO causes oxidation of endogenous thioredoxin as exogenous
      reduced thioredoxin or thioredoxin reductase are required to reduce thioredoxin
      and to restore the catalytic activity of PKC-zeta in PAEC.

PMID- 14674682
TI  - Enhanced glycerol 3-phosphate dehydrogenase activity in adipose tissue of obese
      humans.
AB  - The primary purpose of this investigation was to determine whether adipose tissue
      glycerol 3-phosphate dehydrogenase activity is associated with human obesity. The
      data presented in this paper indicate that the glycerol 3-phosphate dehydrogenase
      activity in adipose tissue from morbidly obese subjects is approximately 2-fold
      higher than from lean individuals. Moreover, positive correlation between adipose
      tissue glycerol 3-phosphate dehydrogenase activity and body mass index (BMI) (r =
      0.5; p < 0.01) was found. In contrast, the adipose tissue fatty acid synthase
      (FAS) and ATP-citrate lyase (ACL) activities in morbidly obese patients are
      significantly lower than in lean subjects. Furthermore, negative correlation
      between adipose tissue FAS activity and BMI (r = -0.3; p < 0.05) as well as
      between ACL activity and BMI (r = -0.3; p < 0.05) was found. These data indicate
      that elevated glycerol 3-phosphate dehydrogenase might contribute to the increase
      of triacylglycerol (TAG) synthesis in obese subjects, however, fatty acids
      necessary for glycerol 3-phosphate esterification must be derived (because of
      lower FAS and ACL activities) mainly from TAG in circulating lipoproteins formed
      in liver (VLDL), and/or from the intake with food (chylomicrons). The conclusion
      is, that the enhanced activity of glycerol 3-phosphate dehydrogenase, and hence
      the generation of more glycerol 3-phosphate in adipose tissue offers a novel
      explanation for increased TAG production in adipose tissue of obese subjects.

PMID- 14674683
TI  - Effects of oxidant-induced injury on heme oxygenase and glutathione in cultured
      aortic endothelial cells from atherosclerosis-susceptible and -resistant Japanese
      quail.
AB  - Recent studies on cultured aortic endothelial cells (AECs) from atherosclerosis
      susceptible (SUS) and -resistant (RES) strains of Japanese quail suggest that
      differences in atherosclerosis susceptibility between RES and SUS may be due to
      differences in endothelial heme oxygenase (HO) and antioxidant components. We
      have now investigated the effects of oxidant-induced injury on HO and glutathione
      (GSH) in AECs from SUS and RES quail. We report that cultured AECs from SUS and
      RES birds differ in their response to oxidative stress. AECs from the SUS strain
      cells are more susceptible than those from the RES strain to oxidative stress
      induced by tert-butylhydroperoxide, as judged by lower HO activity, HO-1
      expression, ferritin and GSH levels. Aortic endothelial cells from SUS birds also
      showed higher levels of catalytic iron, TBARS production and LDH release compared
      with RES cells, indicating that SUS AECs are more susceptible to oxidative stress
      than cells from the resistant strain. Furthermore, independently of genetic
      status, AECs from old birds have higher TBARS and lower levels of HSP70 induction
      than AECs from younger birds, suggesting that aging is associated with a
      decreased ability of AECs to respond to oxidative stress, and this may be
      relevant to the permissive effect of aging on the process of atherogenesis. Our
      results indicate that genetic factors and endogenous antioxidant systems in the
      blood vessel wall may be important in determining the susceptibility of vascular
      cells to oxidative stress and atherosclerotic plaque formation.

PMID- 14674684
TI  - Immunomodulatory and cytoprotective role of RP-1 in gamma-irradiated mice.
AB  - RP-1 has been reported to provide protection against lethal gamma-irradiation in
      mice. The present study was undertaken to understand its mechanism of action,
      especially with respect to modulation of radiation-induced changes in immune cell
      function, plasma antioxidant potential, cell cycle perturbations, apoptosis in
      mouse bone marrow cells, and micronuclei frequency in mice reticulocytes. 2 Gy
      reduced mitogenic response of splenic lymphocytes significantly at 48 h. Pre
      irradiation RP-1 treatment significantly countered the radiation-induced loss of
      splenocyte proliferation. RP-1 treatment, with or without radiation, suppressed
      macrophage activation as compared to control. Irradiation decreased plasma
      antioxidant status significantly (p < 0.05) at 1 and 2 h (4.8 +/- 0.224 and 4.9
      +/- 0.057 mM Fe2+) as compared to control (6.29 +/- 0.733 mM Fe2+) that was
      countered by RP-1 pre-treatment significantly (p < 0.05). RP-1 and irradiation
      individually caused G2 delay in bone marrow cells. RP-1 pre-treatment augmented
      radiation-induced G2 delay and elicited significant (p < 0.05) recovery in S
      phase fraction at 48 h in comparison to irradiated group. Radiation-induced
      apoptosis (3%) was significantly higher than the control. RP-1 pre-treatment
      further enhanced apoptosis frequency (7.2%) in bone marrow cells. RP-1 pre
      treatment significantly (p < 0.05) reduced (1.23%) the radiation-induced MN
      frequency (2.9%) observed at 48 h post-irradiation interval. Since the
      radioprotective manifestation of RP-1 is mediated through multiple mechanisms,
      needs further investigation.

PMID- 14674685
TI  - Humanin improves impaired metabolic activity and prolongs survival of serum
      deprived human lymphocytes.
AB  - Humanin (HN) has been reported to be an endogenous peptide that exerts highly
      selective neuroprotection against cell death induced by various types of
      Alzheimer's disease-related insults. We previously proposed the much broader
      cytoprotective potential of HN from the result that HN suppressed serum
      deprivation-induced death of rat pheochromocytoma cells. In this study, we showed
      that HN also suppressed death of human lymphocytes cultured under serum-deprived
      condition. Further, we revealed, by assaying metabolic activity and survival
      rate, that HN was a potent factor capable of increasing the metabolic activity of
      individual serum-deprived lymphocytes. To our knowledge, there is no report
      described about a rescue factor that increases the metabolic activity of
      individual serum-deprived cells and prolongs their survival. This novel feature
      of HN may enable us to apply this peptide for the management of diseases
      involving poor metabolic activity, such as mitochondria-related disorders and
      brain ischemia.

PMID- 14674686
TI  - A single arginine residue is required for the interaction of the electron
      transferring flavoprotein (ETF) with three of its dehydrogenase partners.
AB  - The interaction of several dehydrogenases with the electron transferring
      flavoprotein (ETF) is a crucial step required for the successful transfer of
      electrons into the electron transport chain. The exact determinants regarding the
      interaction of ETF with its dehydrogenase partners are still unknown. Chemical
      modification of ETF with arginine-specific reagents resulted in the loss, to
      varying degrees, of activity with medium chain acyl-coenzyme A dehydrogenase
      (MCAD). The kinetic profiles showed the inactivations followed pseudo-first-order
      kinetics for all reagents used. For activity with MCAD, maximum inactivation of
      ETF was accomplished by 2,3-butanedione (4% residual activity after 120 min) and
      it was shown that modification of one arginine residue was responsible for the
      inactivation. Almost 100% restoration of this ETF activity was achieved upon
      incubation with free arginine. However, the same 2,3-butanedione modified ETF
      only possessed decreased activity with dimethylglycine-(DMGDH, 44%) and sarcosine
      (SDH, 27%) dehydrogenases unlike the abolition with MCAD. Full protection of ETF
      from arginine modification by 2,3-butanedione was achieved using substrate
      protected DMGDH, MCAD and SDH respectively. Cross-protection studies of ETF with
      the three dehydrogenases implied use of the same single arginine residue in the
      binding of all three dehydrogenases. These results lead us to conclude that this
      single arginine residue is essential in the binding of the ETF to MCAD, but only
      contributes partially to the binding of ETF to SDH and DMGDH and thus, the
      determinants of the dehydrogenase binding sites overlap but are not identical.

PMID- 14674687
TI  - An aging-related cell surface NADH oxidase (arNOX) generates superoxide and is
      inhibited by coenzyme Q.
AB  - This report describes a novel ECTO-NOX protein with an oscillating activity
      having a period length of ca. 26 min encountered with buffy coat fractions and
      sera of aged individuals (70-100 years) that generates superoxide as measured by
      the reduction of ferricytochrome c. The oscillating, age-related reduction of
      ferricytochrome c is sensitive to superoxide dismutase, is inhibited by coenzyme
      Q and is reduced or absent from sera of younger individuals (20-40 years). An
      oscillating activity with a regular period length is a defining characteristic of
      ECTO-NOX proteins (a group of cell surface oxidases with enzymatic activities
      that oscillate). The period length of ca. 26 min is longer than the period length
      of 24 min for the usual constitutive (CNOX) ECTO-NOX proteins of the cell surface
      and sera which neither generate superoxide nor reduce ferricytochrome c. The
      aging-related ECTO-NOX protein (arNOX) provides a mechanism to transmit cell
      surface oxidative changes to surrounding cells and circulating lipoproteins
      potentially important to atherogenesis. Additionally, the findings provide a
      rational basis for the use of dietary coenzyme Q to retard aging-related arterial
      lesions.

PMID- 14674688
TI  - Salubrious effect of low molecular weight heparin on atherogenic diet-induced
      cardiac, hepatic and renal lipid peroxidation and collapse of antioxidant
      defences.
AB  - The present work showcases the distressing picture of oxidative stress in the
      cardiac, hepatic and renal tissues, in an experimental model based on early phase
      atherogenesis. The protection rendered by LMWH intervention forms part of the
      same study. Male Wistar rats of 140 +/- 10 g were categorized as four groups. One
      group served as untreated control and another as LMWH drug control group. Two
      groups were fed a hypercholesterolemic atherogenic diet (rat chow supplemented
      with 4% cholesterol, 1% cholic acid and 0.5% thiouracil; CCT diet) for 2 weeks;
      one of these groups received LMWH treatment of 300 microg/day/rat for 7 days. The
      biochemical index of tissue lipid peroxidation (LPO) was assessed in terms of MDA
      formation. Heart, liver and kidney tissues of CCT-diet fed rats showed
      significantly elevated levels of LPO. In the early phase atherosclerotic group,
      we observed abnormal changes in the activities/levels of tissue enzymic
      (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymic
      (reduced glutathione, ascorbate and alpha-tocopherol) antioxidants. We report
      normalized LPO levels and antioxidant defences in the atherogenic rats treated
      with LMWH. Thus the present study highlights the hepatic, cardiac and renal
      oxidative changes induced by experimental atherogenesis, and the protection
      rendered by LMWH treatment in atherosclerotic cardiovascular conditions.

PMID- 14674689
TI  - Functional analysis of amino acids of the Na+/H+ exchanger that are important for
      proton translocation.
AB  - The Na+/H+ exchanger is an integral membrane protein found in the plasma membrane
      of eukaryotic and prokaryotic cells. In eukaryotes it functions to exchange one
      proton for a sodium ion. In mammals it removes intracellular protons while in
      plants and fungal cells the plasma membrane form removes intracellular sodium in
      exchange for extracellular protons. In this study we used the Na+/H+ exchanger of
      Schizosaccharomyces pombe (Sod2) as a model system to study amino acids critical
      for activity of the protein. Twelve mutant forms of the Na+/H+ exchanger were
      examined for their ability to translocate protons as assessed by a Cytosensor
      microphysiometer. Mutation of the amino acid Histidine 367 resulted in defective
      proton translocation. The acidic residues Asp145, Asp178, Asp266 and Asp267 were
      important in the proton translocation activity of the Na+/H+ exchanger. Mutation
      of amino acids His98, His233 and Asp241 did not significantly impair proton
      translocation by the Na+/H+ exchanger. These results confirm that polar amino
      acids are important in proton flux activity of Na+/H+ exchangers.

PMID- 14674690
TI  - Protective effect of diallyl sulfide on oxidative stress and nephrotoxicity
      induced by gentamicin in rats.
AB  - Gentamicin (GM) is an antibiotic whose clinical use is limited by its
      nephrotoxicity. Experimental evidences suggest a role of reactive oxygen species
      in GM-induced nephrotoxicity. In this work we explored the effect of diallyl
      sulfide (DAS), a garlic-derived compound with antioxidant properties, on GM
      induced nephrotoxicity. Four groups of rats were studied: (1) Control, treated
      intragastrically with olive oil as a vehicle, (2) GM, treated subcutaneously with
      GM (125 mg/kg/day for 4 days), (3) DAS, treated intragastrically with DAS (50
      mg/kg/day for 4 days), and (4) GM + DAS. Nephrotoxicity was made evident by: (1)
      the increase in creatinine and blood urea nitrogen in serum, (2) the increase in
      urinary excretion of N-acetyl-beta-D-glucosaminidase and total protein, and (3)
      necrosis of proximal tubular cells. These functional and structural alterations
      were prevented or ameliorated by DAS treatment. In addition, GM increased levels
      of renal oxidative stress markers nitrotyrosine and protein carbonyl groups which
      were also ameliorated by DAS in GM + DAS group. The mechanism by which DAS has a
      protective effect on GM-induced nephrotoxicity may be related, at least in part,
      to the decrease in oxidative stress in renal cortex.

PMID- 14674691
TI  - Inactivation of acetylcholinesterase by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine hydrochloride.
AB  - The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been
      shown to reversibly inhibit the activity of acetylcholinesterase. The
      inactivation of the enzyme was detected by monitoring the accumulation of yellow
      color produced from the reaction between thiocholine and dithiobisnitrobenzoate
      ion. The kinetic parameter, Km for the substrate (acetylthiocholine), was found
      to be 0.216 mM and Ki for MPTP inactivation of acetylcholinesterase was found to
      be 2.14 mM. The inactivation of enzyme by MPTP was found to be dose-dependent. It
      was found that MPTP is neither a substrate of AChE nor the time-dependent
      inactivator. The studies of reaction kinetics indicate the inactivation of AChE
      to be a linear mixed-type inhibition. The dilution assays indicate that MPTP is a
      reversible inhibitor for AChE. These data suggest that once MPTP enters the basal
      ganglia of the brain, it can inactivate the acetylcholinesterase enzyme and
      thereby increase the acetylcholine level in the basal ganglia of brain, leading
      to potential cell dysfunction. It appears that the nigrostriatal toxicity by MPTP
      leading to Parkinson's disease-like syndrome may, in part, be mediated via the
      acetylcholinesterase inactivation.

PMID- 14674692
TI  - Angiotensin II mediates Tyr-dephosphorylation in rat fetal kidney membranes.
AB  - Angiotensin II (Ang II) elicits a variety of physiological effects through
      specific Ang II receptors in numerous tissues. In addition, Ang II is a modulator
      of cellular growth and exerts a positive or negative effect on cell growth
      depending on which receptor subtype is activated. Expression of the intrarenal
      AT2 receptors occurs at its highest levels in the fetal kidney, with a rapid
      decline after birth. In the present paper, we performed a study on the signaling
      mechanism of Ang II receptors in rat fetal (E20) kidney, a rich source of AT2
      receptors, where both Ang II receptor subtypes are present. Ang II induces Tyr
      dephosphorylation of proteins in rat fetal kidney membranes. The response is dose
      dependent, with a reduction of 20% with respect to the control (100%), signal
      that is completely reversed by Ang IIAT2 competitor PD123319. Orthovanadate, the
      inhibitor of phospho-Tyr-phosphatases (PTPase), reverts Ang II effect, suggesting
      the involvement of a protein tyrosine phosphatase. The peptide analog of Ang II,
      CGP42112, exhibits an agonist effect, which is dose-dependent. Thus, in rat fetal
      (E20) kidney, the Ang-induced protein Tyr-dephosphorylation of several proteins
      is mediated by AT2 receptors, mechanism that involves an orthovanadate sensitive
      PTPase.

PMID- 14674693
TI  - Identification, purification and partial characterization of tissue inhibitor of
      matrix metalloproteinase-1 (TIMP-1) in bovine pulmonary artery smooth muscle.
AB  - Bovine pulmonary artery smooth muscle tissue possesses the tissue inhibitor of
      matrix metalloproteinase-1 (TIMP-1) as revealed by immunoblot studies of the
      cytosolic fraction with polyclonal TIMP-1 antibody. In this report, we described
      the purification and partial characterization of the inhibitor from the cytosolic
      fraction of the smooth muscle. This inhibitor was purified by a series of anion
      exchange, gel filtration and affinity chromatographic procedure. The purified
      inhibitor showed an apparent molecular mass of 30 kDa in SDS-PAGE. Amino terminal
      sequence analysis for the first 22 amino acids of the purified inhibitor was also
      found to be identical to bovine TIMP-1. This glycosylated inhibitor was found to
      be active against matrix metalloproteinase-9 (MMP-9, gelatinase B), the ambient
      matrix metalloproteinase in the pulmonary smooth muscle. The purified TIMP-1 was
      also found to be sensitive to pure rabbit and human fibroblast collagenase and
      type IV collagenase. In contrast, it had minimum inhibitory activity against
      bacterial collagenase. It was also found to be inactive against the serine
      proteases trypsin and plasmin. The inhibitor was heat and acid resistant and it
      had the sensitivity to trypsin degradation and reduction-alkylation.

PMID- 14674694
TI  - Human aurora-B binds to a proteasome alpha-subunit HC8 and undergoes degradation
      in a proteasome-dependent manner.
AB  - Human Aurora/Ipl1-related kinase 2 (Aurora-B) is a key regulator of mitosis. Here
      human proteasome alpha-subunit C8 (HC8) was identified to interact with the
      Aurora-B by yeast two-hybrid screen. This finding was confirmed by GST pull-down
      assays and immunoprecipitation experiments. The Aurora-B protein level increased
      in HeLa cells cultured with proteasome inhibitor ALLN. Our data suggest that
      Aurora-B might undergo degradation by binding to HC8 in a proteasome-dependent
      manner during mitosis.

PMID- 14674695
TI  - Partial prevention of changes in SR gene expression in congestive heart failure
      due to myocardial infarction by enalapril or losartan.
AB  - Although activation of the renin-angiotensin system (RAS) is known to produce
      ventricular remodeling and congestive heart failure (CHF), its role in inducing
      changes in the sarcoplasmic reticulum (SR) protein and gene expression in CHF is
      not fully understood. In this study, CHF was induced in rats by ligation of the
      left coronary artery for 3 weeks and then the animals were treated orally with or
      without an angiotensin converting enzyme inhibitor, enalapril (10 mg/kg/day) or
      an angiotensin II receptor antagonist, losartan (20 mg/kg/day) for 4 weeks. Sham
      operated animals were used as control. The animals were hemodynamically assessed
      and protein content as well as gene expression of SR Ca(2+)-release channel
      (ryanodine receptor, RYR), Ca(2+)-pump ATPase (SERCA2), phospholamban (PLB) and
      calsequestrin (CQS) were determined in the left ventricle (LV). The infarcted
      animals showed cardiac hypertrophy, lung congestion, depression in LV +dP/dt and 
      dP/dt, as well as increase in LV end diastolic pressure. Both protein content and
      mRNA levels for RYR, SERCA2 and PLB were decreased without any changes in CQS in
      the failing heart. These alterations in LV function as well as SR protein and
      gene expression in CHF were partially prevented by treatment with enalapril or
      losartan. The results suggest that partial improvement in LV function by
      enalapril and losartan treatments may be due to partial prevention of changes in
      SR protein and gene expression in CHF and that these effects may be due to
      blockade of the RAS.

PMID- 14674696
TI  - Polyhydroxyalkanoate (PHA) biosynthesis in Thermus thermophilus: purification and
      biochemical properties of PHA synthase.
AB  - The biosynthesis of polyhydroxyalkanoates (PHAs) was studied, for the first time,
      in the thermophilic bacterium Thermus thermophilus. Using sodium gluconate (1.5%
      w/v) or sodium octanoate (10 mM) as sole carbon sources, PHAs were accumulated to
      approximately 35 or 40% of the cellular dry weight, respectively. Gas
      chromatographic analysis of PHA isolated from gluconate-grown cells showed that
      the polyester (Mw: 480,000 g mol(-1)) was mainly composed of 3-hydroxydecanoate
      (3HD) with a molar fraction of 64%. In addition, 3-hydroxyoctanoate (3HO), 3
      hydroxyvalerate (3HV) and 3-hydroxybutyrate (3HB) occurred as constituents. In
      contrast, the polyester (Mw: 391,000 g mol(-1)) from octanoate-grown cells was
      composed of 24.5 mol% 3HB, 5.4 mol% 3HO, 12.3 mol% 3-hydroxynonanoate (3HN), 14.6
      mol% 3HD, 35.4 mol% 3-hydroxyundecanoate (3HUD) and 7.8 mol% 3-hydroxydodecanoate
      (3HDD). Activities of PHA synthase, a beta-ketothiolase and an NADPH-dependent
      reductase were detected in the soluble cytosolic fraction obtained from gluconate
      grown cells of T. thermophilus. The soluble PHA synthase was purified 4271-fold
      with 8.5% recovery from gluconate-grown cells, presenting a Km of 0.25 mM for 3HB
      CoA. The optimal temperature of PHA synthase activity was about 70 degrees C and
      acts optimally at pH near 7.3. PHA synthase activity was inhibited 50% with 25
      microM CoA and lost all of its activity when it was treated with alkaline
      phosphatase. T. thermophilus PHA synthase, in contrary to other reported PHA
      synthases did not exhibit a lag phase on its kinetics, when low concentration of
      the enzyme was used. Incubation of PHA synthase with 1 mM N-ethyl-maleimide
      inhibits the enzyme 56%, indicating that cysteine might be involved in the
      catalytic site of the enzyme. Acetyl phosphate (10 mM) activated both the native
      and the dephosphorylated enzyme. A major protein (55 kDa) was detected by SDS
      PAGE. When a partially purified preparation was analyzed on native PAGE the major
      band exhibiting PHA synthase activity was eluted from the gel and analyzed
      further on SDS-PAGE, presenting the first purification of a PHA synthase from a
      thermophilic microorganism.

PMID- 14674697
TI  - Effects of barium and 5-hydroxydecanoate on the electrophysiologic response to
      acute regional ischemia and reperfusion in rat hearts.
AB  - The aim of this work was to investigate the role of the inward rectifying (K1)
      and the sarcolemmal ATP-sensitive K+ (K-ATP) channels in the electrical response
      to regional ischemia and the subsequent development of ventricular
      tachyarrhythmias on reflow (RA). Surface electrograms (ECG) and the transmembrane
      potential from subepicardial left ventricular cells were recorded in
      spontaneously beating rat hearts perfused with buffer alone (controls) or exposed
      to 100 microM BaCl2 or 100 microM 5-hydroxydecanoate (5-HD) to block either K1 or
      K-ATP channels respectively. After 20 min of equilibration and 10 min of control
      recordings, the left anterior descending coronary artery was occluded for 10 min.
      This was followed by reperfusion. The effects of regional ischemia as well as
      those of reperfusion (10 min) were recorded throughout. In the three groups,
      ischemia induced a modest decrease in heart rate and a sharp reduction in resting
      potential within 3 min. The latter as well as the accompanying depression of
      propagated electrical activity were enhanced by Ba2+. A partial recovery of the
      resting potential was observed in all groups during the last 2 min of coronary
      occlusion. Concomitantly, a slight reduction in the action potential duration was
      found in the control hearts. This effect was blocked by 5-HD. Under Barium the
      action potential duration increased by a factor of 3 and its ischemic variations
      were minimized. Severe sustained ventricular tachyarrhythmias developed on reflow
      in the controls and in the 5-HD exposed hearts. Barium limited the duration of
      arrhythmic episodes to a few seconds. Our data indicate that the initial
      electrical effects of ischemia are unrelated to activation of ATP sensitive K+
      channels and that gK1 dominates the K+ membrane conductance at this stage.
      Furthermore, they show that action potential lengthening limits the duration of
      arrhythmic episodes triggered by reperfusion. This suggests that electrical
      heterogeneity plays an important role in the perpetuation of reperfusion
      arrhythmias.

PMID- 14674698
TI  - Forskolin up-regulates metastasis-related phenotypes and molecules via protein
      kinase B, but not PI-3K, in H7721 human hepato-carcinoma cell line.
AB  - Forskolin (FSK) is known as an up-regulator of intracellular cAMP and inhibitor
      of cancer growth and metastasis. The effects of FSK on the metastasis potential
      and its mechanisms were studied using a human hepatocarcinoma cell line, H7721.
      It was found that FSK stimulated cell growth, increased cAMP in the cells, and
      enhanced the metastasis-related phenotypes, including adhesion to laminin (Ln)
      and human umbilical vein epithelial cells (HUVEC), chemotactic migration and
      invasion. These effects were supposed to result from the increase of the SLex
      expression induced by FSK, since only the monoclonal antibody of SLex showed a
      significant attenuation of the enhanced metastasis-associated phenotypes. Using
      H7721 cells transfected with the sense or antisense cDNA of protein kinase B
      (PKB) and some inhibitors of signal transduction, it was discovered that FSK up
      regulated the expression of SLex via PKB, but it was independent of
      phosphotidylinositide-3-kinase (PI-3K). A subtype of atypical protein kinase C (a
      PKC) might also participate in the up-regulation of SLex expression by FSK, and
      cAMP/PKA pathway is a negative regulator of SLex expression on H7721 cells. It
      can be concluded that FSK shows a metastasis-promoting effect ex vivo.

PMID- 14674699
TI  - Commitment to apoptosis by ceramides depends on mitochondrial respiratory
      function, cytochrome c release and caspase-3 activation in Hep-G2 cells.
AB  - Apoptosis and necrosis are distinct forms of cell death that occur in response to
      various agents. We studied the action of N-Acetyl-D-sphingosine (C2-ceramide) or
      N-hexanoyl-D-sphingosine (C6-ceramide) in human hepatoma HepG2 cell line. The
      cells were treated in vitro for 1-24 h. Cell toxicity was evaluated by MTT assay.
      DNA content was estimated by gel electrophoresis and flow cytometry. Measurement
      of mitochondrial respiration, analysis of cytochrome c release and caspase-3
      activation were assessed in order to determine if either of these events in the
      induction of apoptosis and/or necrosis was predominant. We have demonstrated that
      C2 and C6-ceramide were cytotoxic in a time and dose-dependent manner. After 24 h
      of treatment with 100 microM of C2 and C6 the morphology (May-Giemsa staining) of
      treated cells displayed an apoptotic phenotype in C6-treated cells, confirmed by
      a high (sub-G1 peak > 20%) proportion by flow cytometry while a necrotic
      morphology was observed after C2-ceramide treatment, confirmed by DNA smearing in
      DNA electrophoresis. After C6-ceramide incubation, the respiratory chain was
      functional only slightly inhibited (20%), there was production of ATP, cytochrome
      c release without ROS production, activation of caspase-3 and induction of
      apoptosis. On the contrary, C2-ceramide inhibited the respiratory chain more
      intensely (80%) increased significantly ROS production, which resulted in an
      arrest of ATP production, no cytochrome c release and absence of caspase-3
      activation. Finally after complete exhaustion of intracellular ATP, mitochondrial
      explosion induced necrotic cell death. In conclusion, evidence suggest that
      mitochondrial respiratory chain function is essential for controlling the
      decision of the cell to enter a apoptotic or necrosis process.

PMID- 14674700
TI  - NaCN-induced chemical hypoxia is associated with altered gene expression.
AB  - Sodium cyanide (NaCN)-induced chemical hypoxia is known to increase intracellular
      free calcium concentration and reduce cell survival, but its effect on gene
      expression has not been studied. In this study, we designed primers to conduct a
      rapid and reliable assay for the expression of mRNA of inducible nitric oxide
      synthase (iNOs), tumor suppressor protein p53, Bcl-2, heat shock protein 70 (HSP
      70), and beta-actin in human intestinal epithelial T84 cells and Jurkat T cells.
      NaCN-induced chemical hypoxia increased iNOs and HSP-70 mRNA in both types of
      cells, whereas p53 and Bcl-2 mRNA were singularly induced in T84 cells and Jurkat
      T cells, respectively. In both cell types, treatment of hypoxic cells with a
      reversible selective iNOs inhibitor, Now-nitro-L-arginine (LNNA), blocked iNOs,
      Bcl-2, and HSP-70 mRNA, but increased p53. The NaCN-induced hypoxia was also
      found to increase caspase-3 cellular activity in both cell types. Treatment with
      LNNA alone decreased the basal caspase-3 cellular activity. A prior treatment of
      LNNA significantly inhibited the NaCN-induced increase in the cellular activity
      of this apoptotic enzyme. This is the first report to show that NaCN-induced
      chemical hypoxia alters both stress-related gene expression and caspase-3
      cellular activity and can be regulated by the iNOs inhibitor LNNA. Since NaCN has
      been included in the 'National chemical terrorism threat' list, by the US
      Department of Defense, our studies provide useful insight in the development of
      molecular sensors to detect early exposure to this chemical terrorism threat.

PMID- 14674701
TI  - Genetic characterization of a new splice variant of the beta2 subunit of the
      voltage-dependent calcium channel.
AB  - This study reports a novel splice variant form of the voltage-dependent calcium
      channel beta2 subunit (beta2g). This variant is composed of the conserved amino
      terminal sequences of the beta2a subunit, but lacks the beta-subunit interaction
      domain (BID), which is thought essential for interactions with the alpha1
      subunit. Gene structure analysis revealed that this gene was composed of 13
      translated exons spread over 107 kb of the genome. The gene structure of the
      beta2 subunit was similar in exon-intron organization to the murine beta3 and
      human beta4 subunits. Electrophysiological evaluation revealed that beta2a and 2g
      affected channel properties in different ways. The beta2a subunit increased the
      peak amplitude, but failed to increase channel inactivation, while beta2g had no
      significant effects on either the peak current amplitude or channel inactivation.
      Other beta3 subunits, such as beta3 and beta4, significantly increased the peak
      current and accelerated current inactivation.

PMID- 14674702
TI  - Effects of L-carnitine and its derivatives on postischemic cardiac function,
      ventricular fibrillation and necrotic and apoptotic cardiomyocyte death in
      isolated rat hearts.
AB  - The study aimed to examine whether L-carnitine and its derivatives, acetyl-L
      carnitine and propionyl-L-carnitine, were equally effective and able to improve
      postischemic cardiac function, reduce the incidence of reperfusion-induced
      ventricular fibrillation, infarct size, and apoptotic cell death in
      ischemic/reperfused isolated rat hearts. There are several studies indicating
      that L-carnitine, a naturally occurring amino acid and an essential cofactor, can
      improve mechanical function and substrate metabolism not only in hypertrophied or
      failing myocardium but also in ischemic/reperfused hearts. The effects of L
      carnitine, acetyl-L-carnitine, and propionyl-L-carnitine, on the recovery of
      heart function, incidence of reperfusion-induced ventricular fibrillation (VF),
      infarct size, and apoptotic cell death after 30 min ischemia followed by 120 min
      reperfusion were studied in isolated working rat hearts. Hearts were perfused
      with various concentrations of L-carnitine (0.5 and 5 mM), acetyl-L-carnitine
      (0.5 and 5 mM), and propionyl-L-carnitine (0.05, 0.5, and 5 mM), respectively,
      for 10 min before the induction of ischemia. Postischemic recovery of CF, AF, and
      LVDP was significantly improved in all groups perfused with 5 mM of L-carnitine,
      acetyl-L-carnitine, and propionyl-L-carnitine. Significant postischemic
      ventricular recovery was noticed in the hearts perfused with 0.5 mM of propionyl
      L-carnitine, but not with the same concentration of L-carnitine or L-acetyl
      carnitine. The incidence of reperfusion VF was reduced from its control value of
      90 to 10% (p < 0.05) in hearts perfused with 5 mM of propionyl-L-carnitine only.
      Other doses of various carnitines failed to reduce the incidence of VF. The
      protection in CF, AF, LVDP, and VF reflected in a reduction in infarct size and
      apoptotic cell death in hearts treated with various concentrations of carnitine
      derivatives. The difference between effectiveness of various carnitines on the
      recovery of postischemic myocardium may be explained by different membrane
      permeability properties of carnitine and its derivatives.

PMID- 14674703
TI  - Comparative effects of a vasopeptidase inhibitor vs. an angiotensin converting
      enzyme inhibitor on cardiomyocyte apoptosis in rats with heart failure.
AB  - Apoptosis is involved in ventricular remodeling after myocardial infarction (MI).
      We investigated the effects of the vasopeptidase inhibitor (VPI) omapatrilat on
      cardiomyocyte apoptosis and compared it to the angiotensin converting enzyme
      inhibitor (ACEI) captopril in the rat post-MI model and in cultured neonatal rat
      cardiomyocytes. Wistar males rats surviving 4 h post-MI were assigned to
      omapatrilat (40 or 80 mg/kg/day), captopril (160 mg/kg/day) or no treatment.
      After 56 days, hemodynamic measurements were performed (n = 96) and rats were
      sacrificed. One group had assessment of cardiac remodeling and detection of DNA
      fragments by in situ end labelling method (ISEL), while the other had morphologic
      measurements and DNA laddering assessed. In addition, cultured neonatal rat
      cardiomyocytes (n = 6) were treated for 72 h with vehicle, captopril or
      omapatrilat in the presence or absence of the apoptosis inducing agent H2O2.
      Omapatrilat and captopril resulted in similar improvements of hemodynamic
      measurements, ventricular weight and dilatation, cardiac fibrosis and myocardial
      cell cross-section in large MI rats. Omapatrilat increased scar thickness more
      than did captopril. All sham-operated groups had little evidence of apoptosis. In
      the large MI group, there was a significant increase in ISEL-positive cells in
      the control (0.095 +/- 0.016%) and captopril (0.124 +/- 0.024%) groups in
      comparison with control sham-operated (0.006 +/- 0.006%), but this increase was
      limited to the peri-MI area. Omapatrilat (0.012 +/- 0.012% for both doses)
      prevented the increase in apoptosis in the peri-MI area. Also, omapatrilat but
      not captopril reduced DNA laddering in large MI. Moreover, in cultured neonatal
      rat cardiomyocytes, omapatrilat but not captopril reduced apoptosis as assessed
      by DNA laddering. The VPI omapatrilat, with its combination of NEP and ACE
      inhibition, suppresses cardiomyocyte apoptosis post-MI and in neonatal cultured
      rat cardiomyocytes more than the ACEI captopril, but this does not result in
      significant hemodynamic or morphologic differences between omapatrilat and
      captopril.

PMID- 14674704
TI  - Cardiotrophin-1: expression in experimental myocardial infarction and potential
      role in post-MI wound healing.
AB  - Cardiotrophin-1 (CT-1), a member of the IL-6 family of cytokines, has been shown
      to be elevated in the serum of patients with ischemic heart disease and valvular
      heart disease, and induces cardiomyocyte hypertrophy in vitro. We investigated
      expression of CT-1 in post-MI rat heart and the effect of CT-1 on cultured
      primary adult rat cardiac fibroblasts. Elevated CT-1 expression was observed in
      the infarct zone at 24 h and continued through 2, 4 and 8 weeks post-MI, compared
      to sham-operated animals. CT-1 induced rapid phosphorylation of Jak, Jak2, STAT1,
      STAT3, p42/44 MAPK and Akt in cultured adult cardiac fibroblasts. CT-1 induced
      cardiac fibroblast protein synthesis and proliferation. Protein and DNA synthesis
      were dependent on activation of Jak/STAT, MEK1/2, PI3K and Src pathways as
      evidenced by decreased 3H-leucine and 3H-thymidine incorporation after
      pretreatment with AG490, PD98059, LY294002 and genistein respectively.
      Furthermore, CT-1 treatment increased procollagen-1-carboxypropeptide (PICP)
      synthesis, a marker of mature collagen synthesis. CT-1 induced cell migration of
      rat cardiac fibroblasts. Our results suggest that CT-1, as expressed in post-MI
      heart, may play an important role in infarct scar formation and ongoing
      remodeling of the scar. CT-1 was able to initiate each of the processes
      considered important in the formation of infarct scar including cardiac
      fibroblast migration as well as fibroblast proliferation and collagen synthesis.
      Further work is required to determine factors that induce CT-1 expression and
      interplay with other mediators of cardiac infarct wound healing in the setting of
      acute cardiac ischemia and chronic post-MI heart failure.

PMID- 14674705
TI  - PKB phosphorylation and survivin expression are cooperatively regulated by
      disruption of microfilament cytoskeleton.
AB  - Changes in cell shape can lead to detachment and cell death, and the disruption
      in the actin cytoskeletal network, as one marker of cell shape changes, can
      itself induce apoptosis. In this study, the effects of cytochalasin B on the
      apoptosis-related proteins, protein kinase B and survivin were investigated.
      Apoptosis induced by disruption of microfilaments with cytochalasin B was found,
      although it happened at a low level, to simultaneously occur with G2/M arrest in
      50% of the cytochalasin B-treated cells. During apoptosis, PKB phosphorylation
      and survivin expression were decreased by cytochalasin B, and the decline in
      survivin expression was preceded by PKB dephosphorylation, which implicated that
      survivin may be a target of PKB protein. The G2/M arrest of cytochalasin B
      treated cells may be the direct function of cytochalasin B to microfilaments or
      the subsequent inhibition of survivin expression, or both. These results suggest
      that PKB/survivin signaling pathway may be responsible for the apoptosis induced
      by the disruption of actin cytoskeleton.

PMID- 14674706
TI  - Direct inhibition of neutral endopeptidase in vasopeptidase inhibitor-mediated
      amelioration of cardiac remodeling in rats with chronic heart failure.
AB  - Vasopeptidase inhibitors possess dual inhibitory actions on neutral endopeptidase
      (NEP) and angiotensin-converting enzyme (ACE) and have beneficial effects on
      cardiac remodeling. However, the contribution of NEP inhibition to their effects
      is not yet fully understood. To address the role of cardiac NEP inhibition in the
      anti-remodeling effects of a vasopeptidase inhibitor, we examined the effects of
      omapatrilat on the development of cardiac remodeling in rats with left coronary
      artery ligation (CAL) and those on collagen synthesis in cultured fibroblast
      cells. In vivo treatment with omapatrilat (30 mg/kg/day for 5 weeks) inhibited
      cardiac NEP activity in rats with CAL, which was associated with a suppression of
      both cardiac hypertrophy and collagen deposition. In cultured cardiac
      fibroblasts, omapatrilat (10(-7) to approximately 10(-5) M) inhibited NEP
      activity and augmented the ANP-induced decrease in [3H]-proline incorporation.
      ONO-BB, an active metabolite of the NEP selective inhibitor ONO-9902, also
      augmented the ANP-induced response, whereas captopril, an ACE inhibitor, did not.
      The angiotensin I-induced increase in [3H]-proline incorporation was prevented by
      omapatrilat and captopril, but not by ONO-BB. The results suggest that
      vasopeptidase inhibitor suppressed cardiac remodeling in the setting of chronic
      heart failure, possibly acting through the direct inhibition of cardiac NEP.
      Vasopeptidase inhibitors may have therapeutic advantages over the classical ACE
      and NEP inhibitors alone with respect to the regression of cardiac fibrosis.

PMID- 14674707
TI  - Identification, purification and partial characterization of tissue inhibitor of
      matrix metalloproteinase-2 in bovine pulmonary artery smooth muscle.
AB  - Bovine pulmonary artery smooth muscle possesses the tissue inhibitor of matrix
      metalloproteinase-2 (TIMP-2) as revealed by Western immunoblot study of its
      cytosol fraction with bovine polyclonal TIMP-2 antibody. This potent polypeptide
      inhibitor of matrix metalloproteinases (MMPs) was purified to homogeneity from
      cytosol fraction of bovine pulmonary artery smooth muscle. This inhibitor was
      purified by ammonium sulfate precipitation followed by gelatin sepharose and
      lentil lectin sepharose affinity chromatography and continuous elution
      electrophoresis by Prep Cell Model 491 (Bio-Rad, USA). SDS-PAGE revealed that the
      inhibitor has an apparent molecular mass of 21 kDa and was confirmed as TIMP-2 by
      (i) Western immunoblot assay using bovine polyclonal TIMP-2 antibody; and also by
      (ii) amino terminal amino acid sequence analysis of the purified inhibitor is
      found to be identical with TIMP-2 obtained from other sources. The purified 21
      kDa inhibitor was found to be active against matrix metalloproteinase-2 (MMP-2,
      72 kDa gelatinase) and matrix metalloproteinase-9 (MMP-9, 92 kDa gelatinase), the
      ambient MMPs in the pulmonary artery smooth muscle. The inhibitor was also found
      to be sensitive to the activated 72 kDa gelatinase-TIMP-2 complex and also active
      human interstitial collagenase. By contrast, it was found to be insensitive to
      the serine proteases: trypsin and plasmin. The inhibitor was heat and acid
      resistant and it had the sensitivity to trypsin degradation and reduction
      alkylation. Treatment of the inhibitor with hydrogen peroxide, superoxide
      generating system (hypoxanthine plus xanthine oxidase) and peroxynitrite
      inactivated the inhibitor.

PMID- 14674708
TI  - Curcumin inhibits ultraviolet light induced human immunodeficiency virus gene
      expression.
AB  - Recently, we reported that the herbal drug St. John's Wort is a potent inhibitor
      of UV-induced HIV-LTR activation in stably transfected HIVcat/HeLa cells. Our
      previous studies have demonstrated that the activation of p38 MAP kinase (stress
      activated protein kinase-2) and NF-kappaB are both required for a full UV-induced
      HIV gene expression response. In this study we have investigated the mechanism by
      which curcumin inhibits UV-activated HIV-LTR gene expression. We found that
      treatment of HIVcat/HeLa cells with micromolar concentrations of curcumin
      completely abolished UV activation of HIV gene expression. Curcumin treatment at
      similar doses as those used to inhibit HIV gene expression also effectively
      blocked UV activation of NF-kappaB, as demonstrated by electrophoretic mobility
      shift assay. In contrast, curcumin did not inhibit UV-induced phosphorylation of
      p38 MAP kinase. This observation was also supported by findings that curcumin did
      not inhibit UV-induced phosphorylation of CREB/ATF-1 and ATF-2. Although curcumin
      was ineffective in preventing UV-induced p44/42 MAP kinase phosphorylation, the
      JNK (1 and 2) and AP-1 activation were efficiently blocked by curcumin in HeLa
      cells. We conclude that the mechanism by which curcumin modulates UV activation
      of HIV-LTR gene expression mainly involves the inhibition of NF-kappaB
      activation.

PMID- 14674709
TI  - Regulation of phagocytic process of macrophages by noradrenaline and its end
      metabolite 4-hydroxy-3-metoxyphenyl-glycol. Role of alpha- and beta
      adrenoreceptors.
AB  - The regulatory capacity of noradrenaline and its end metabolite 4-hydroxy-3
      metoxyphenylglycol (HMPG) on the complete phagocytic process of macrophages were
      investigated. Either noradrenaline or HMPG did not modify adherence. However, 10(
      12) M of noradrenaline stimulated the chemotaxis of macrophages, mainly mediated
      by alpha-adrenergic receptors. In contrast, 10(-12) M of HMPG induced an opposed
      effect on this stage of the phagocytic process. To stimulate phagocytosis, it is
      necessary to employ a higher concentration (10(-5) M) of noradrenaline and this
      effect was blocked with either 10(-6) M propranolol or 10(-6) M phentolamine, and
      maintained by HMPG. Noradrenaline and HMPG did not modify the microbicide
      capacity of macrophages (measured by O2- production after phagocytosis). In
      conclusion, noradrenaline modulates the phagocytic process of macrophages, and
      this modulation is completed by HMPG, maintaining the phagocytic functions at
      physiologically optimal levels. Modulation of chemotaxis is mainly mediated by
      alpha-receptors and phagocytosis needs both alpha- and beta-receptor-stimulation.

PMID- 14674710
TI  - Noradrenaline and its end metabolite 3-methoxy-4-hydroxyphenylglycol inhibit
      lymphocyte chemotaxis: role of alpha- and beta-adrenoreceptors.
AB  - The capacity of noradrenaline (NA) and its end metabolite 3-methoxy-4
      hydroxyphenylglycol (MHPG) to modulate the chemotaxis of lymphocytes from a
      primary immunocompetent organ (thymus) and a secondary one (spleen) was
      investigated over a range of concentrations from 10(-12) M to 10(-5) M.
      Lymphocyte chemotaxis was evaluated in a Boyden chamber. The results indicated
      that 10(-5) M of NA inhibits the chemotaxis of lymphocytes from both the
      immunocompetent organs studied, and that this effect is blocked by either
      propranolol (10(-6) M) or phentolamine (10(-5) M). Similarly, 10(-5) M of MHPG
      induced a decrease in the chemotaxis capacity of the lymphocytes. In conclusion,
      high physiological concentrations of NA and its end metabolite modulate the
      mobility of lymphocytes, and the participation of both alpha and beta
      adrenoreceptors is necessary, showing a new aspect of neuroimmune interactions.

PMID- 14674711
TI  - Glycogen metabolism in rat heart muscle cultures after hypoxia.
AB  - Elevated glycogen levels in heart have been shown to have cardioprotective
      effects against ischemic injury. We have therefore established a model for
      elevating glycogen content in primary rat cardiac cells grown in culture and
      examined potential mechanisms for the elevation (glycogen supercompensation).
      Glycogen was depleted by exposing the cells to hypoxia for 2 h in the absence of
      glucose in the medium. This was followed by incubating the cells with 28 mM
      glucose in normoxia for up to 120 h. Hypoxia decreased glycogen content to about
      15% of control, oxygenated cells. This was followed by a continuous increase in
      glycogen in the hypoxia treated cells during the 120 h recovery period in
      normoxia. By 48 h after termination of hypoxia, the glycogen content had returned
      to baseline levels and by 120 h glycogen was about 150% of control. The increase
      in glycogen at 120 h was associated with comparable relative increases in glucose
      uptake (approximately 180% of control) and the protein level of the glut-1
      transporter (approximately 170% of control), whereas the protein level of the
      glut-4 transporter was decreased to < 10% of control. By 120 h, the hypoxia
      treated cells also exhibited marked increases in the total (approximately 170% of
      control) and fractional activity of glycogen synthase (control, approximately
      15%; hypoxia-treated, approximately 30%). Concomitantly, the hypoxia-treated
      cells also exhibited marked decreases in the total (approximately 50% of control)
      and fractional activity of glycogen phosphorylase (control, approximately 50%;
      hypoxia-treated, approximately 25%). Thus, we have established a model of
      glycogen supercompensation in cultures of cardiac cells that is explained by
      concerted increases in glucose uptake and glycogen synthase activity and
      decreases in phosphorylase activity. This model should prove useful in studying
      the cardioprotective effects of glycogen.

PMID- 14674712
TI  - Salt-induced hypertension in WKY rats: prevention by alpha-lipoic acid
      supplementation.
AB  - There is strong evidence that points to excess dietary salt as a major factor
      contributing to the development of hypertension. Salt sensitivity is associated
      with glucose intolerance and insulin resistance in both animal models and humans.
      In insulin resistance, impaired glucose metabolism leads to elevated endogenous
      aldehydes which bind to vascular calcium channels, increasing cytosolic [Ca2+]i
      and blood pressure. In an insulin resistant animal model of hypertension,
      spontaneously hypertensive rats (SHRs), dietary supplementation with lipoic acid
      lowers tissue aldehydes and plasma insulin levels and normalizes blood pressure.
      The objective of this study is to examine the effects of a high salt diet on
      tissue aldehydes, cytosolic [Ca2+]i and blood pressure in WKY rats and to
      investigate whether dietary supplementation with lipoic acid can prevent a salt
      induced increase in blood pressure. Starting at 7 weeks of age, WKY rats were
      divided into three groups of six animals each and treated for 10 weeks with diets
      as follows: WKY-normal salt (0.7% NaCl); WKY-high salt (8% NaCl); WKY-high salt +
      lipoic acid (8% NaCl diet + lipoic acid 500 mg/Kg feed). At completion, animals
      in the high salt group had elevated systolic blood pressure, platelet [Ca2+]i,
      and tissue aldehyde conjugates compared with the normal salt group and showed
      smooth muscle cell hyperplasia in the small arteries and arterioles of the
      kidneys. Dietary alpha-lipoic acid supplementation in high salt-treated WKY rats
      normalized systolic blood pressure and cytosolic [Ca2+]i and aldehydes in liver
      and aorta. Kidney aldehydes and renal vascular changes were attenuated, but not
      normalized.

PMID- 14674715
TI  - The effect of vitamin E on the response of rabbit bladder smooth muscle to
      hydrogen peroxide.
AB  - There is increasing evidence that ischemia, reperfusion, and the generation of
      free radicals are major etiological factors in the progression of bladder
      dysfunction after partial outlet obstruction. In vitro studies demonstrated that
      the magnitude of contractile dysfunction following exposure of bladder smooth
      muscle to hypoxia followed by re-oxygenation was related to the level of lipid
      peroxidation indicating that membrane lipid peroxidation participated in the
      contractile failure induced. Recent studies demonstrated that incubation of
      isolated strips of bladder smooth muscle with hydrogen peroxide (H2O2) result in
      progressive contractile dysfunctions and is associated with progressive increases
      in MDA (peroxidation product). The current study investigates if feeding rabbits
      a diet high in vitamin E protects the bladder from the effects of in vitro H2O2.
      Sixty-four male New Zealand White rabbits were separated into two groups: The
      rabbits in group 1 were fed a normal diet (28 rabbits) whereas the rabbits in
      group 2 were placed on a diet enriched with alpha-tocopherol (36 rabbits). After
      3 weeks on the normal or high E diet, each rabbit was anesthetized and the
      bladder excised and cut into 6 isolated strips of bladder detrusor. Each strip
      was mounted in individual 15 ml baths containing oxygenated Tyrode's solution.
      The contractile responses to field stimulation (FS), carbachol. and KCl were
      determined. The strips were washed and exposed to one of the following
      concentrations of hydrogen peroxide (H2O2): 0% (control), 0.0625, 0.125, 0.25,
      0.5, 1.0 and 3.0% for a period of 1 h. At the end of the hour each strip was
      washed free of H2O2 and a second set of contractile responses were performed and
      compared to the first set. At the end of the experiment, each strip was frozen
      and stored at -70 degrees C for analysis of malondialdehyde (MDA) as a measure of
      peroxidation. In both groups, H2O2 produced similar dose dependent decreases in
      the contractile responses to all forms of stimulation. In the normal-diet group
      H2O2 produced a dose dependent increase in MDA formation, whereas in the high E
      group there were no increases in MDA at any concentration of H2O2. Feeding
      rabbits a diet high in vitamin E protected the bladder smooth muscle from
      peroxidation, but had no significant effect on the contractile dysfunctions
      mediated by direct incubation with H2O2.

PMID- 14674714
TI  - Dose- and time-dependent effects of a novel (-)-hydroxycitric acid extract on
      body weight, hepatic and testicular lipid peroxidation, DNA fragmentation and
      histopathological data over a period of 90 days.
AB  - (-)-Hydroxycitric acid (HCA), a natural extract from the dried fruit rind of
      Garcinia cambogia (family Guttiferae), is a popular supplement for weight
      management. The dried fruit rind has been used for centuries as a condiment in
      Southeastern Asia to make food more filling and satisfying. A significant number
      of studies highlight the efficacy of Super CitriMax (HCA-SX, a novel 60% calcium
      potassium salt of HCA derived from Garcinia cambogia) in weight management. These
      studies also demonstrate that HCA-SX promotes fat oxidation, inhibits ATP-citrate
      lyase (a building block for fat synthesis), and lowers the level of leptin in
      obese subjects. Acute oral, acute dermal, primary dermal irritation and primary
      eye irritation toxicity studies have demonstrated the safety of HCA-SX. However,
      no long-term safety of HCA-SX or any other (-)-hydroxycitric acid extract has
      been previously assessed. In this study, we have evaluated the dose- and time
      dependent effects of HCA-SX in Sprague-Dawley rats on body weight, hepatic and
      testicular lipid peroxidation, DNA fragmentation, liver and testis weight,
      expressed as such and as a % of body weight and brain weight, and
      histopathological changes over a period of 90 days. The animals were treated with
      0, 0.2, 2.0 and 5.0% HCA-SX as feed intake and the animals were sacrificed on 30,
      60 or 90 days of treatment. The feed and water intake were assessed and
      correlated with the reduction in body weight. HCA-SX supplementation demonstrated
      a reduction in body weight in both male and female rats over a period of 90 days
      as compared to the corresponding control animals. An advancing age-induced
      marginal increase in hepatic lipid peroxidation was observed in both male and
      female rats as compared to the corresponding control animals. However, no such
      difference in hepatic DNA fragmentation and testicular lipid peroxidation and DNA
      fragmentation was observed. Furthermore, liver and testis weight, expressed as
      such and as a percentage of body weight and brain weight, at 30, 60 and 90 days
      of treatment, exhibited no significant difference between the four groups. Taken
      together, these results indicate that treatment of HCA-SX over a period of 90
      days results in a reduction in body weight, but did not cause any changes in
      hepatic and testicular lipid peroxidation, DNA fragmentation, or
      histopathological changes.

PMID- 14674713
TI  - A modest glucokinase overexpression in the liver promotes fed expression levels
      of glycolytic and lipogenic enzyme genes in the fasted state without altering
      SREBP-1c expression.
AB  - Hepatic genes crucial for carbohydrate and lipid homeostasis are regulated by
      insulin and glucose metabolism. However, the relative contributions of insulin
      and glucose to the regulation of metabolic gene expression are poorly defined in
      vivo. To address this issue, adenovirus-mediated hepatic overexpression of
      glucokinase was used to determine the effects of increased hepatic glucose
      metabolism on gene expression in fasted or ad libitum fed rats. In the fasted
      state, a 3 fold glucokinase overexpression was sufficient to mimic feeding
      induced increases in pyruvate kinase and acetyl CoA carboxylase mRNA levels,
      demonstrating a primary role for glucose metabolism in the regulation of these
      genes in vivo. Conversely, glucokinase overexpression was unable to mimic feeding
      induced alterations of fatty acid synthase, glucose-6-phosphate dehydrogenase,
      carnitine palmitoyl transferase I or PEPCK mRNAs, indicating insulin as the
      primary regulator of these genes. Interestingly, glucose-6-phosphatase mRNA was
      increased by glucokinase overexpression in both the fasted and fed states,
      providing evidence, under these conditions, for the dominance of glucose over
      insulin signaling for this gene in vivo. Importantly, glucokinase overexpression
      did not alter sterol regulatory element binding protein 1-c mRNA levels in vivo
      and glucose signaling did not alter the expression of this gene in primary
      hepatocytes. We conclude that a modest hepatic overexpression of glucokinase is
      sufficient to alter expression of metabolic genes without changing the expression
      of SREBP-1c.

PMID- 14674716
TI  - Co-inheritance of specific genotypes of HSPG and ApoE gene increases risk of type
      2 diabetic nephropathy.
AB  - The objective of this paper is to investigate co-inheritance of specific HSPG and
      ApoE genotypes in the development of Chinese type 2 diabetic nephropathy. PCR
      RFLP was used to detect HSPG and ApoE genotypes in 385 Chinese subjects including
      298 patients with type 2 diabetes mellitus (T2DM) and 87 non-diabetic controls
      (Non-DM). The T2DM group was subdivided into patients with (TDN; n = 218) and
      without diabetic nephropathy (Non-DN; n = 80). The latter group was further
      subdivided into groups of patients with microalbuminuria nephropathy (DN-1; n =
      129) and severe diabetic nephropathy (DN-2; n = 89). We then compared the
      relative frequencies of various HSPG and ApoE genotypes and alleles among the
      groups, searching for predictive trends. The T allele of the HSPG gene occurred
      more frequently in the DN-2 group than in the Non-DN or DN-1 groups, their
      Fisher's exact p was 1.05 x 10(-3) and 6.58 x 10(-6); odds ratios were 2.09 (95%
      CI 1.32-3.30) and 2.48 (95% CI 1.64-3.74), respectively. The E2 allele of the
      ApoE gene occurred more frequently in the T2DM than in the Non-DM group, the
      Fisher's exact p was 0.0087; odds ratio was 3.45 (95% CI 1.30-9.81). Genotype
      analysis showed that the TT or TG of HSPG gene were paired with the E2/2 or E2/3
      of ApoE gene significantly more frequently in the TDN group than in the Non-DN
      group, with an odds ratio of 3.03 (95% CI 1.03-8.90). There was no significant
      differences in other combinations of genotypes in HSPG and ApoE genes between TDN
      and Non-DN group. These results suggest that the HSPG T allele is a risk factor
      for the development of severe diabetic nephropathy in type 2 diabetic patients,
      and that the ApoE E2 allele is a risk factor for the occurrence of type 2
      diabetes mellitus in Chinese general population. In addition, we find that co
      inheritance of T/E2 confers a higher risk of type 2 diabetes mellitus progression
      to diabetic nephropathy in Chinese.

PMID- 14674717
TI  - APRT from erythrocytes of HGPRT deficient patients: kinetic, regulatory and
      thermostability properties.
AB  - Adenine phosphoribosyltransferase (APRT) has been 1200-fold purified from
      erythrocytes of a patient with partial hipoxanthine-guanine
      phosphoribosyltransferase (HGPRT) deficiency, Propositus, and in those of a
      controlHPRT+, with 20% efficiency in both proteins and specific activity of 550
      and 243 nmol/h/mgprotein. The specific activity determined in the Propositus
      enzyme was, in all purification steps, higher than that of the controlHPRT+.
      Significant changes were found in their thermal stabilities. Half inactivation
      times at each temperature studied are greater for the Propositus enzyme in the
      temperature interval 60-80 degrees C. No significant difference has been observed
      in the affinity constants for adenine and PRPP substrates. Studies on inhibition
      by the reaction product suggest that AMP is a competitive inhibitor with respect
      to PRPP in both enzymes, with Ki values of 150 microM in Propositus and 220
      microM in controlHPRT+.

PMID- 14674718
TI  - Men with acquired hypogonadotropic hypogonadism treated with testosterone may be
      fertile.
AB  - Men with acquired hypogonadotropic hypogonadism treated with testosterone are
      generally assumed to be infertile. The finding of two such patients with
      unexpected fertility and normal sperm counts prompted an evaluation of
      spermatogenesis in additional men with this condition. Case records were
      initially searched and one similar case with fertility was found. Subsequently,
      12 consecutive men with acquired hypogonadotropic hypogonadism were evaluated for
      gonadal function and sperm production while receiving testosterone. In five of
      the cases with proven spermatogenesis, exon 10 of the FSH receptor was sequenced
      to look for activating mutations. The original three cases and four of the
      subsequent 12 men had sperm concentrations > or = 15 million/ml. Two additional
      men had concentrations of 1 million/ml and six were azoospermic. Residual LH and
      FSH levels were slightly higher in those with maintained spermatogenesis prior to
      testosterone replacement. No activating mutations were found in exon 10 of the
      FSH receptor in the five cases studied. We conclude that men with acquired
      hypogonadotropic hypogonadism being treated with testosterone should not be
      assumed to be sterile, as we have found that more than half have been shown to
      have persistent spermatogenesis with more than one-third having sperm
      concentrations > or = 15 million/ml. This may be related to fact that
      gonadotropin levels in such patients are present, albeit low. Semen analyses in
      such men should be routinely carried out so that they can be appropriately
      counseled regarding potential fertility.

PMID- 14674719
TI  - The treatment of de novo acromegalic patients with octreotide-LAR: efficacy,
      tolerability and cardiovascular effects.
AB  - AIM: Somatostatin analogues are normally used as adjunctive therapy to surgery
      and radiotherapy in management of acromegaly. We studied the effects of de novo
      OCT-LAR treatment on growth hormone (GH) suppression, tumour size, cardiovascular
      function, clinical symptoms, signs and quality of life in 9 newly diagnosed
      acromegalic patients. METHODS: Patients commenced OCT-LAR 20 mg IM monthly for 2
      months. Dose increased to 30 mg monthly if mean serum GH (MGH) > 5 mU/l (2
      microg/litre) (7 patients). Treatment continued for 6 months. Cardiac function
      assessed by echocardiography at baseline and day 169. Left ventricular (LV) mass
      and ejection fraction (EF) calculated from 2D M-mode studies. RESULTS: Serum GH
      demonstrated suppression in 8/9 patients (mean suppression 64.9% +/- 29.7%,
      range; 4-95.2%). MGH suppressed < 5 mU/ (2 microg/litre) in 3 (33%) patients. IGF
      I and IGFBP3 normalised in 1 (12.5%) and 3 (38%) patients respectively. Tumour
      shrinkage seen in 30% patients. Eight patients were assessed by echocardiography.
      At baseline, 7 patients demonstrated abnormalities in LV mass and EF. At day 169,
      6 patients demonstrated a fall and 1 an increase in LV mass. Overall there was no
      significant change in LV mass. A significant increase in EF was observed (p =
      0.02). There were significant improvements in health perception (p = 0.01),
      fatigue (p < 0.05) and perspiration (p = 0.0039). CONCLUSIONS: These data
      demonstrate OCT-LAR provides adequate control of acromegaly in a proportion of
      patients treated over 6 months. This is associated with improved LV function,
      evidenced by increased EF. Improved results are expected with longer-term
      treatment. OCT-LAR may be considered as primary treatment for acromegaly in
      selected patients.

PMID- 14674720
TI  - Dopamine resistance of prolactinomas.
AB  - Resistance to dopamine agonists can be defined with respect to failure to
      normalize PRL levels and failure to decrease tumor size by > or = 50%. Using
      these definitions, failure to normalize PRL levels is seen in 24% of those
      treated with bromocriptine, 13% of those treated with pergolide and 11% of those
      treated with 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. Studies of in vitro cell
      preparations show that the D2 receptors of resistant tumors are decreased in
      number but have normal affinity. Treatment approaches for resistant patients
      include switching to another dopamine agonist and raising the dose of the drug as
      long as there is continued response to the dose increases and no adverse effects.
      Transsphenoidal surgery can also be done. If fertility is desired, clomiphene,
      gonadotropins, and GnRH are also options. If fertility is not desired, 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.
      However, in many cases modest or even no reduction may be acceptable long-term 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- 14674721
TI  - Improvement of acromegaly after octreotide LAR treatment.
AB  - Octreotide is a somatostatin analog that inhibits growth hormone release showing
      higher potency than natural somatostatin so it has proved to be effective in
      acromegaly treatment. The objective of present study was to establish the effects
      of octreotide LAR (long acting release) preparation in patients with active
      acromegaly. The following parameters were assessed: clinical response, safety of
      medication, GH and IGF-1 serum concentrations and pituitary tumor size. Eleven
      patients (6 men and 5 women) range 41.4 years old with diagnosis of active
      acromegaly were included. Octreotide was administered at 0.1 mg subcutaneusly
      dose three times daily for four weeks to test the drug tolerability. Afterwards
      patients received octreotide LAR 20 mg intramuscularly separated by 28 days
      periods with an option to continue for 8 months. Basal average GH serum
      concentrations was 27.6 ng/mL. After 6 months treatment reduction to 5.03 +/-
      5.38 ng/mL in 9 patients (p < 0.001) was observed. Basal IGF-1 average serum
      concentration was 889.55 +/- 167.29 ng/mL with a reduction value to 483.00 +/-
      239.71 ng/mL in 9 of 11 patients after 6 months treatment (p < 0.005). The drug
      was well tolerated with few adverse effects Diarrhea, flatulence and steatorrhea
      were observed during the administration of subcutaneous octreotide in 18.2% of
      patients. Two patients had symptomatic biliary lithiasis that was successfully
      removed by surgery. Clinical symptoms improved and some of them dissapeared such
      as headaches and sweatings. Tumor shrinkage was observed in 66.7% of cases.
      Monthly injections of 20 mg of octreotide LAR were effective to reduce GH and IGF
      1 levels in patients with active acromegaly accompanied by improvement of
      clinical symptoms and significant tumor size reduction.

PMID- 14674722
TI  - Prolactin, psychological stress and environment in humans: adaptation and
      maladaptation.
AB  - Non-puerperal lactation and/or hyperprolactinemia in humans have been related to
      psychological variables in a variety of ways: (1) Non-puerperal nursing; (2)
      Pseudopregnancy; (3) Rapid weight gain; (4) Psychogenic galactorrhea; (5) Acute
      prolactin responses to psychological stress; (6) High prolactin levels in persons
      who cope passively in real life stress situations; (7) Paternal deprivation in
      women with pathological hyperprolactinemia; (8) Clinical onset of prolactinomas
      following life-events. Publications on the above subjects are scattered in the
      literature as curiosities, anecdotal case-reports or unexplained associations, as
      there is no theoretical frame of reference to accommodate them. We propose that
      prolactin is a component of a biological, "maternal", subroutine, adaptive to the
      care of the young, which promotes accumulation of fat for the extraordinary
      expenses of pregnancy and lactation, the production of milk and maternal
      behavior. In an attempt to characterize the stimuli responsible for the
      activation of the maternal subroutine in the absence of pregnancy we studied the
      hormonal profiles of female volunteers during three types of sessions under
      hypnosis: (1) Relaxation-only, control sessions; (2) Sessions in which a fantasy
      of "nursing" was induced; (3) Sessions of evocations of memories. Prolactin
      surges were related to the evocation, with rage, of humiliating experiences, but
      not with the fantasy of nursing. Cortisol surges were related to surprise and
      shock and were negatively associated with prolactin. In conclusion--Prolactin and
      cortisol are measurable markers of two different, and alternative, coping
      strategies to "psychological stress".

PMID- 14674723
TI  - Corticotroph carcinoma presenting as a silent corticotroph adenoma.
AB  - Malignant pituitary tumours are rare and their pathogenesis is not fully
      understood. We have performed genetic analyses on tissues arising from a
      pituitary carcinoma that initially presented as a silent corticotroph adenoma but
      which failed to respond to repeated, aggressive surgical and medical therapy.
      Loss of heterozygosity (LOH) of known or putative tumour suppressor genes (TSG)
      was assessed by microsatellite analysis of microdissected tumour and matched
      patient blood DNA. Clonality of the pituitary tumour samples was analysed by two
      PCR-based techniques; one employing the highly polymorphic short tandem repeat
      (STR) within the human androgen receptor allele (HUMARA), another based on a
      restriction fragment length polymorphism of the X chromosome phosphoglycerokinase
      (PGK-1) gene. Screening with 9 microsatellite markers demonstrated allelic loss
      at 3 sites (D1S190, D3S1283 and D10S297) in all tumour samples except the
      presenting pituitary tumour. X chromosome inactivation analysis demonstrated
      polyclonality in the original presenting tumour and a metastatic deposit but
      monoclonality in tissue samples from a second and third transsphenoidal
      resection. In these cases of tumour recurrence both LOH and X chromosome
      inactivation suggest that monoclonality arose from preferential clonal growth
      from the original polyclonal tumour. Polyclonality of the metastatic deposit
      suggests that this was derived from the presenting tumour, although the LOH
      pattern indicates that a single clone dominates. The data are consistent with
      increasing allelic loss associated with tumour dedifferentiation and malignant
      transformation.

PMID- 14674724
TI  - Symptomatic pneumocephalus occurring years after transphenoidal surgery and
      radiation therapy for an invasive pituitary tumor: a case report and review of
      the literature.
AB  - We present the unusual case of a patient who experienced a CSF leak and
      subsequent pneumocephalus several years after transphenoidal surgery and
      radiation treatment for an ACTH secreting pituitary tumor. This patient underwent
      aggressive management including placement of a lumbar drain, and reoperation to
      stop her leak. Despite these efforts, her leak persisted resulting in significant
      tension pneumocephalus. Pneumocephalus is a rare but important potential
      complication of transphenoidal surgery. Here we discuss our management of this
      patient's condition, and review the existing literature.

PMID- 14674725
TI  - Effect of gamma knife radiosurgery on a pituitary gonadotroph adenoma: a
      histologic, immunohistochemical and electron microscopic study.
AB  - The morphologic findings in a pituitary macroadenoma removed from a 65-year old
      man by the transsphenoidal approach 9 months after gamma knife surgery are
      reported. The tumor was immunoreactive for FSH beta and showed ultrastractural
      features consistent with an oncocytic gonadotroph adenoma. Accumulation of
      connective tissue separating small groups of adenoma cells was evident. Several
      dilated vessels and numerous vascular endothelial growth factor immunopositive
      adenoma cell were noted. By electron microscopy the endothelial linings
      frequently showed discontinuities with platelet accumulation attached to the
      gaps. Several vessels were severely injured showing necrosis of endothelial
      cells. It can be concluded that gamma knife surgery caused severe alterations in
      pituitary adenoma microcirculation indicating that vascular injury plays a
      crucial role in tumor shrinkage.

PMID- 14674726
TI  - Bouts of responding from variable-interval reinforcement of lever pressing by
      rats.
AB  - Four rats obtained food pellets by lever pressing. A variable-interval
      reinforcement schedule assigned reinforcers on average every 2 min during one
      block of 20 sessions and on average every 8 min during another block. Also, at
      each variable-interval duration, a block of sessions was conducted with a
      schedule that imposed a variable-ratio 4 response requirement after each variable
      interval (i.e., a tandem variable-time variable-ratio 4 schedule). The total rate
      of lever pressing increased as a function of the rate of reinforcement and as a
      result of imposing the variable-ratio requirement. Analysis of log survivor plots
      of interresponse times indicated that lever pressing occurred in bouts that were
      separated by pauses. Increasing the rate of reinforcement increased total
      response rate by increasing the rate of initiating bouts and, less reliably, by
      lengthening bouts. Imposing the variable-ratio component increased response rate
      mainly by lengthening bouts. This pattern of results is similar to that reported
      previously with key poking as the response. Also, response rates within bouts
      were relatively insensitive to either variable.

PMID- 14674727
TI  - Stimulus generalization of behavioral history.
AB  - Undergraduates responded under a variable-ratio 30 schedule in the presence of a
      25-mm long line and on a differential-reinforcement-of-low-rate 6-s schedule when
      a 13-mm long line was present. Following this, a line-length continuum
      generalization test was administered under a fixed-interval 6-s schedule
      (Experiment 1) or extinction (Experiment 2). In both experiments, obtained
      generalization gradients conformed to typical postdiscrimination gradients.
      Responses were frequent under stimuli physically similar to the 25-mm line and
      infrequent under stimuli physically similar to the 13-mm line. The generalization
      gradients were generally asymmetric with peak response rates occurring at line
      lengths greater than 25 mm.

PMID- 14674728
TI  - Choice in a variable environment: effects of unequal reinforcer distributions.
AB  - Six pigeons were trained in a procedure in which sessions included seven
      unsignaled components, each offering two pecking keys, and each providing a
      potentially different reinforcer ratio between the two keys. Across conditions,
      various combinations of reinforcer ratios and reinforcer-magnitude ratios were
      used to create unequal reinforcer distributions between the two alternatives when
      averaged across a session. The results extended previous research using the same
      basic procedure that had included only reinforcer distributions symmetrical
      around 1:1. Data analyses suggested that the variables controlling choice
      operated at a number of levels: First, individual reinforcers had local effects
      on choice; second, sequences of successive reinforcers obtained at the same
      alternative (continuations) had cumulative effects; and, third, when these
      sequences themselves occurred with greater frequency, their effects further
      cumulated. A reinforcer obtained at the other alternative following a sequence of
      continuations (a discontinuation) had a large effect and apparently reset choice
      to levels approximating the sessional reinforcer ratio.

PMID- 14674729
TI  - Speech perception in rats: use of duration and rise time cues in labeling of
      affricate/fricative sounds.
AB  - The voiceless affricate/fricative contrast has played an important role in
      developing auditory theories of speech perception. This type of theory draws some
      of its support from experimental data on animals. However, nothing is known about
      differential responding of affricate/fricative continua by animals. In the
      current study, the ability of hooded rats to "label" an affricate/fricative
      continuum was tested. Transfer (without retraining) to analogous nonspeech
      continua was also tested. The nonspeech continua were chosen so that if transfer
      occurred, it would indicate whether the animals had learned to use rise time or
      duration cues to differentiate affricates from fricatives. The data from 9 of 10
      rats indicated that rats can discriminate between these cues and do so in a
      similar manner to human subjects. The data from 9 of 10 rats also demonstrated
      that the rise time of the stimulus was the basis of the discrimination; the
      remaining rat appeared to use duration.

PMID- 14674730
TI  - Recency, repeatability, and reinforcer retrenchment: an experimental analysis of
      resurgence.
AB  - Four experiments were conducted with pigeons to assess the experimental
      conditions necessary for the occurrence of resurgence. The general procedure
      consisted of the following conditions: Condition 1--reinforcement of key pecking;
      Condition 2--reinforcement of treadle pressing and concurrent extinction of key
      pecking; and Condition 3--the resurgence condition wherein resurgence was defined
      as the recovery of key pecking. In Experiments 1 and 2, the resurgence condition
      was conventional extinction. The effect of recency on resurgence magnitude was
      examined in Experiment 1 by manipulating the number of sessions of Condition 2,
      above. Resurgence was not a function of recency with the parameters used.
      Repeating the three conditions revealed resurgence to be a repeatable effect in
      Experiment 2. In Experiment 3, a variable-time schedule was in effect for the
      resurgence condition. Resurgence was not produced by response-independent food
      delivery. In Experiment 4, the resurgence condition was a variable-interval
      schedule for treadle pressing that arranged a lower reinforcement rate than in
      Condition 2 (92% reduction in reinforcers per minute). Resurgence was lower in
      magnitude relative to conventional extinction, although resurgence was obtained
      with 2 out of 3 pigeons. The results are discussed in terms of the variables
      controlling resurgence and the relations between behavioral history, resurgence,
      and other forms of response recovery.

PMID- 14674731
TI  - Rapid acquisition of preference in concurrent chains.
AB  - We report two experiments using a concurrent-chains procedure in which one
      terminal-link schedule was fixed-interval 8 s and the alternative schedule
      changed randomly from day to day. In Experiment 1, the alternative schedule
      varied between 4 s and 16 s according to a pseudorandom binary sequence similar
      to the one used by Hunter and Davison (1985). Similar to results with concurrent
      schedules, pigeons' response allocation in the initial link was most sensitive to
      the schedules arranged in the current session, although some effect of prior
      history was evident. Overall sensitivity was lower than for comparable data from
      steady-state research. In Experiment 2, a unique value between 2 s and 32 s was
      used for the alternative-schedule delay in each session. Sensitivity levels were
      similar to Experiment 1 and remained unchanged across 61 sessions of training.
      For all subjects, sensitivity was greater when the alternative-schedule delay was
      greater than 8 s compared with when it was less than 8 s. Generalized-matching
      plots revealed evidence of clustering of data points into two groups for some
      pigeons, suggesting that a process similar to a categorical discrimination may
      have at least partly determined response allocation. Overall, this research shows
      that pigeons' initial-link response allocation can adjust rapidly to frequent
      changes in the terminal links.

PMID- 14674732
TI  - Variable-interval reinforcement schedule value influences responding following
      REM sleep deprivation.
AB  - The effects of rapid-eye movement sleep deprivation (REMSD) in rats were studied
      in relation to variable-interval (VI) reinforcement schedule value. Initially,
      lever pressing was maintained on a VI 30-s schedule of food pellet delivery.
      After a baseline was established, rats were repeatedly exposed to 96 hr of REMSD
      and control conditions of an equivalent duration. Responding decreased following
      REMSD but not after exposure to control conditions. Lever pressing was then
      maintained on a VI 15-s schedule of food pellet delivery and exposure to the
      REMSD and control conditions was repeated. Under this condition following
      repeated REMSD exposures, rates of lever pressing became similar to baseline
      responding. A VI 30-s schedule of food pellet delivery was then reinstated and
      REMSD and control conditions were repeated. Lever pressing following exposure to
      the REMSD condition decreased for 3 of 4 rats. Results suggest that VI schedule
      value influences the effects of REMSD on responding.

PMID- 14674733
TI  - Intake of vitamins A, C, and E from diet and supplements and breast cancer in
      postmenopausal women.
AB  - OBJECTIVE: The influence of the vitamins A, C, and E on breast cancer development
      has not been clarified. An effect of a vitamin per se implicates similar patterns
      for the effects of the vitamin from dietary and supplemental sources. We examined
      how the breast cancer incidence rate among postmenopausal women was related to
      intake of vitamins A, C, and E from diet and supplements. METHODS: Data was
      sampled as case-control nested within the Danish 'Diet, Cancer and Health'
      cohort. Data on vitamin intakes were collected at entry into the cohort by means
      of self-administered questionnaires. Women eligible for the nested case-control
      study were postmenopausal at entry into the cohort. The analyses were based on
      418 cases of incident breast cancer and 394 controls (including two cases).
      RESULTS: Breast cancer was not significantly related to the intakes of vitamin A
      or E, whereas a monotonic dose-response relation was seen for the intake of
      vitamin C. The estimated rate ratio per 100 mg vitamin C was: 2.06 (95% CI: 1.45
      2.91) for dietary intake and 1.06 (95% CI: 1.01-1.13) for supplemental intake.
      CONCLUSIONS: We found no evidence of an association between breast cancer and
      intake of vitamin A or E for postmenopausal women. For vitamin C we found an
      increase in breast cancer rate with increasing intake.

PMID- 14674734
TI  - Diet and vitamin or mineral supplements and risk of renal cell carcinoma in
      Canada.
AB  - OBJECTIVE: To assess the role of diet and vitamin or mineral supplements in renal
      cell carcinoma (RCC) risk. METHODS: Mailed questionnaires were completed by 1279
      (691 male and 588 female) newly diagnosed histologically confirmed RCC cases and
      5370 (2696 male and 2674 female) population controls between 1994 and 1997 in
      eight Canadian provinces. Measurement included information on socioeconomic
      status, smoking habits, alcohol use, diet, and vitamin or mineral supplements.
      Odds ratios (ORs) and 95% confidence intervals (CIs) were derived through
      unconditional logistic regression. RESULTS: A significant inverse association
      with RCC was observed with increasing total consumption of vegetables and
      vegetable juices for males and females combined. Increased consumption for two
      specific vegetable groups was inversely associated among females but not males:
      for females, the adjusted ORs for the highest quartile of consumption compared
      with the lowest were 0.5 (95% CI = 0.4-0.7) and 0.6 (95% CI = 0.4-0.8), p <
      0.0001 and p = 0.0002 for dark-green vegetables and cruciferous vegetables,
      respectively. An increased risk was observed (for males and females combined)
      with increased consumption of hamburger and sausage: adjusted ORs for highest
      level versus lowest level were 1.4 (95% CI = 1.1-1.8) and 1.5 (95% CI = 1.2-2.0),
      respectively, p = 0.003 and 0.01. Beef, pork or lamb as a main dish and processed
      meats were also associated with increased RCC. Red meats and processed meats had
      a positive association with RCC among males who had smoked or were overweight;
      among females this was the case for hamburger only. Significant inverse
      associations were observed for females taking vitamin E or calcium supplements.
      Among males, those taking vitamin E or iron for more than 5 years had reduced
      risks. CONCLUSIONS: Our findings add to the evidence that diet may play an
      important role in the etiology of RCC; the risk of RCC may be reduced by changes
      in nutritional habits.

PMID- 14674735
TI  - Residential and occupational exposure to 50 Hz magnetic fields and hematological
      cancers in Norway.
AB  - OBJECTIVE: The aim of this nested case-control study was to test the hypothesis
      that exposure to electromagnetic fields from high-voltage power lines increases
      the incidence of hematological cancers in adults. Data from an occupational
      exposure matrix was also used. METHODS: The study population comprised subjects
      aged 16 and above who had lived in a residence situated in a broad corridor
      around a high-voltage power line in 1980, or one of the years from 1986 to 1996.
      The cases were incident cases diagnosed 1980-1996. Two controls were matched to
      each case by year of birth, sex, municipality and first year entering the cohort.
      Time-weighted average exposure to residential magnetic fields generated by the
      power lines was calculated for the exposure follow-up from January 1, 1967 until
      diagnosis using cut-off points at 0.05 and 0.20 microT. In addition, job titles
      and industrial branch was classified as categories of hours per week in a
      magnetic field above background (0.1 microT). Subjects exposures were cumulated
      over occupationally active years for the exposure follow-up January 1, 1955 until
      diagnosis. RESULTS: When residential magnetic fields are evaluated, the two upper
      residential time weighted average magnetic field categories showed non
      significant elevated odds ratios (ORs) for all leukemia combined (OR: 1.3, 95%
      confidence interval (CI) 0.7-2.5 and OR: 1.5, 95% CI: 0.8-3.0). The increased
      risk was confined to chronic lymphocytic leukemia, acute lymphocytic and acute
      myeloid leukemia. Lymphoma showed a non-significant lower OR in the upper
      exposure category. Multiple myeloma showed non-significant elevated ORs.
      Occupational exposure showed no significant association to exposure for any site.
      CONCLUSIONS: Some elevated ORs were observed in the present study, but the
      results are based on small numbers and no firm conclusions can be drawn.

PMID- 14674736
TI  - Relation of serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3
      to risk of prostate cancer (United States).
AB  - OBJECTIVE: Insulin-like growth factor I (IGF-I) exerts potent mitogenic and
      antiapoptotic effects on prostatic epithelial cells. Insulin-like growth factor
      binding protein-3 (IGFBP-3) modulates the effects of IGF-I, and independently
      induces apoptosis and inhibits cell growth. Previous studies have inconsistently
      associated IGF-I and IGFBP-3 with prostate cancer. To try and further clarify
      these potential associations, we undertook a sibling-matched case-control study.
      METHODS: Serum IGF-I and IGFBP-3 were determined for 845 men (408 cases and 437
      sibling controls). Conditional logistic regression was used to estimate odds
      ratios (ORs) and 95% confidence intervals (CIs) for the association between the
      serum IGF levels and prostate cancer. RESULTS: Among all study subjects, only the
      molar ratio of IGF-I to IGFBP-3 was associated with prostate cancer: comparing
      those in the highest to lowest quartiles gave an OR = 1.62 (95% CI = 1.02-2.57,
      trend-p = 0.04). Among men with clinically less aggressive disease, we observed
      positive associations between prostate cancer and high levels of IGF-I (OR =
      2.78, 95% CI = 1.06-6.80, trend-p = 0.03), and IGFBP-3 (OR = 2.68, 95% CI = 1.08
      6.80, trend-p = 0.04). Simultaneously modeling both left the IGF-I result
      essentially unchanged, while substantially weakening the IGFBP-3 association.
      CONCLUSIONS: We found that a high IGF-I to IGFBP-3 molar ratio was associated
      with an increased risk of prostate cancer. Furthermore, high IGF-I was associated
      with increased risk of prostate cancer among men with less advanced disease at
      diagnosis. These results lend support to the hypothesis that IGF-I, or the IGF-I
      to IGFBP-3 molar ratio, is an important risk factor for prostate cancer.

PMID- 14674737
TI  - Cancer prevention for working class, multi-ethnic populations through health
      centers: the healthy directions study.
AB  - BACKGROUND: This paper presents the study design and baseline data from Healthy
      Directions-Health Centers (HCs), a study designed to address social contextual
      factors in cancer prevention interventions for working class, multi-ethnic
      populations. This study is part of the Harvard Cancer Prevention Program Project.
      METHODS: Ten community HCs were paired and randomly assigned to intervention or
      control. Patients who resided in low income, multi-ethnic neighborhoods were
      identified and approached for participation. This study targeted fruit and
      vegetable consumption, red meat consumption, multi-vitamin intake, and physical
      activity. The intervention components consisted of: (1) a brief in-person study
      endorsement from the participant's clinician at a scheduled routine care visit;
      (2) an initial in-person counseling session with a health advisor; (3) four
      follow-up telephone counseling sessions; (4) multiple mailings of tailored
      materials; and (5) linkages to relevant activities in the local community.
      RESULTS: Fifteen percent of the sample smoked, 86% reported eating fewer than
      five servings of fruits and vegetables per day, 50% reported eating more than the
      recommended amounts of red meat, 40% did not meet recommended physical activity
      levels, and 63% did not take a multi-vitamin on a daily basis. Although overall
      social support was high, participants reported low levels of social norms for the
      target prevention behaviors. Other social contextual mediators and modifying
      factors are reported. CONCLUSIONS: By examining the relationships between social
      contextual factors and health behaviors, it may be possible to enhance the
      effectiveness of interventions aimed at reducing social inequalities in risk
      behaviors.

PMID- 14674738
TI  - Hypothesis: is antibiotic use associated with breast cancer?
AB  - The hypothesis that antibiotic use may increase cancer risk was first proposed
      several decades ago and some research suggests an increased risk of breast cancer
      among women with conditions likely to require long-term antibiotic use (e.g.,
      acne, recurrent urinary-tract infections, UTI). However, this hypothesis has not
      been verified and the possible biological mechanisms are not entirely clear. A
      recent cohort study in Finland reported an increased risk of breast-cancer
      associated with antibiotic use for UTI. The effect of antibiotics on the ability
      of intestinal microflora to metabolise phytochemicals from edible plants into
      compounds that may protect against cancer was proposed as a potential mechanism.
      We extend this hypothesis by proposing that antibiotic use may be associated with
      breast-cancer risk through effects on immune and inflammatory factors, such as
      cytokines, T lymphocytes, prostaglandins, and matrix metalloproteinases, as well
      as disruption of phytochemical and oestrogen metabolism by intestinal microflora.
      We suggest that some mechanisms may increase breast-cancer risk, while others may
      decrease risk, depending on the antibiotic classification.

PMID- 14674739
TI  - Cancer prevention for working class, multiethnic populations through small
      businesses: the healthy directions study.
AB  - OBJECTIVE: We report demographic and social contextual characteristics of
      multiethnic, blue-collar workers from the baseline survey of a study conducted in
      24 small businesses. We discuss ways in which we incorporated these
      characteristics into the design of the intervention. METHODS: We used a
      randomized controled design, with 12 small businesses assigned to a social
      contextual intervention and 12 to a minimum intervention control condition. The
      response rates to the survey were 84% at baseline (n = 1717). Primary outcomes
      included reduction in red meat consumption and increase in physical activity and
      daily multivitamin intake. Secondary outcomes targeted reduction in smoking and
      occupational exposures. RESULTS: The majority of the respondents were male
      (67.6%). This was an ethnically diverse sample with 24.7% representing
      racial/ethnic groups other than white and 43.6% of participants or their parents
      born outside of the US. To meet study recommendations, workers needed improvement
      in all behaviors measured. Participants reported a smoking rate of 25.8, 86.2%
      ate fewer than 5 servings of fruits and vegetables a day 69.5% ate more than
      three servings of red meat a week, 46.8% engaged in less than 2.5 h a week and
      72.4% reported that they did not consume a daily multivitamin. CONCLUSIONS:
      Interventions that address the contextual environment in which health behaviors
      occur, may provide a method that researchers and practitioners can use to reduce
      health disparities.

PMID- 14674740
TI  - Race, socioeconomic status and stage at diagnosis for five common malignancies.
AB  - BACKGROUND: African-Americans are more likely than Caucasians to be diagnosed at
      an advanced stage of colorectal, lung, breast, cervical, and prostate cancers.
      This study explores if racial differences in stage at diagnosis can be explained
      by socioeconomic status (SES) differences. Previous studies investigating this
      association have used aggregate SES indicators from census tract of residence; we
      used census block-group data, representing a smaller, potentially more homogenous
      group. METHODS: We included all African-American and Caucasian invasive cancers
      of the colon and rectum, lung and bronchus, female breast, cervix uteri, and
      prostate that were diagnosed between January 1, 1988 and December 31, 1992 in the
      Detroit area. Stage of disease at diagnosis was grouped as local or non-local. An
      SES value was calculated for each case using aggregate 1990 US Census data for
      education, poverty status, and occupation specific to each case's census block
      group. Logistic regression analysis was used to model the probability of non
      local stage using SES, race, age group, and sex as covariates. RESULTS: SES was
      an independent predictor of stage at diagnosis for each cancer site, with cases
      from the highest SES block-group more likely to present with local stage disease
      than those from the lowest SES group. Race independently predicted stage only for
      breast and prostate cancers; African-Americans presented with more advanced stage
      than Caucasians. CONCLUSIONS: Based on census block-group aggregate data, SES is
      an important predictor of stage at diagnosis, most likely accounting for much of
      the disparity in stage between African-Americans and Caucasians for colorectal,
      lung, and cervical cancers. Biological factors may play a role in racial
      disparities for breast and prostate cancer stage at diagnosis.

PMID- 14674741
TI  - Tea intake and risk of colon cancer in African-Americans and whites: North
      Carolina colon cancer study.
AB  - OBJECTIVES: Tea polyphenols have been shown to exhibit anti-cancer activity, but
      the epidemiological findings are inconsistent. We examined the association
      between tea consumption and colon cancer in a population-based study in North
      Carolina. METHODS: The analysis included 630 cases and 1040 controls frequency
      matched to cases by age, gender, and race. The odds ratios (OR) for tea
      consumption, adjusted for age and gender, were calculated for African-Americans
      and Whites and effect modification by race was explored. RESULTS: No association
      was found between tea consumption and colon cancer overall. Compared to non
      consumers, those who consumed <2 servings/day or > or = 2 servings/day had OR =
      0.9 (95% CI: 0.7-1.2) and OR = 1.3 (95% CI: 0.9-1.8) respectively. Other risk
      factors for colorectal cancer (family history of colorectal cancer, exposure to
      non-steroid anti-inflammatory drugs, meat cooking practices, smoking, physical
      activity, body mass index, intake of red meat, fruits, vegetables, and alcoholic
      beverages) did not influence these associations. We did not find any evidence of
      effect modification by race on either on the multiplicative or additive scale.
      CONCLUSION: We conclude that, contrary to expectation, tea drinking did not
      decrease the risk of colon cancer in this study population.

PMID- 14674742
TI  - A pooled analysis of case-control studies of thyroid cancer: cigarette smoking
      and consumption of alcohol, coffee, and tea.
AB  - OBJECTIVE: To analyze the role of smoking, alcohol, coffee and tea in relation to
      thyroid cancer, we conducted a pooled analysis of 14 case-control studies
      conducted in the United States, Europe, and Asia. METHODS: The sample consisted
      of 2725 thyroid cancer cases (2247 females, 478 males) and 4776 controls (3699
      females, 1077 males). Conditional logistic regression with stratification on
      study, age at diagnosis, and gender was used to compute odds ratios and 95%
      confidence intervals. RESULTS: Thyroid cancer risk was reduced in persons who had
      ever smoked. The relationship was more pronounced in current smokers (OR = 0.6,
      95% CI = 0.6-0.7) than former smokers (OR = 0.9, 95% CI = 0.8-1.1). There were
      significant trends of reduced risk with greater duration and frequency of
      smoking. For consumption of wine and beer, there was a significant trend of
      decreasing thyroid cancer risk (p = 0.02) that was not maintained after
      adjustment for current smoking (p = 0.12). Thyroid cancer risk was not associated
      with consumption of coffee or tea. These findings were consistent in both gender
      specific and histology-specific (papillary and follicular) analyses. CONCLUSIONS:
      Pooled analyses of these geographically diverse case-control data indicate a
      reduced thyroid cancer risk associated with current smoking. A reduced risk
      associated with alcohol was eliminated after adjustment for smoking, and
      caffeinated beverages did not alter thyroid cancer risk.

PMID- 14674743
TI  - Thyroid cancer pooled analysis from 14 case-control studies: what have we
      learned?

PMID- 14674744
TI  - Pleural mesothelioma incidence in Europe: evidence of some deceleration in the
      increasing trends.
AB  - OBJECTIVE: To summarize the geographical and temporal variations in incidence of
      pleural mesothelioma in Europe, using the extensive data available from European
      general cancer registries, and consider these in light of recent trends in
      asbestos extraction, use and import in European countries. MATERIAL AND METHODS:
      The data were extracted from the European Cancer Incidence and Mortality database
      (EUROCIM). The inclusion criteria was acceptance in Volume VII of Cancer
      Incidence in Five Continents. Truncated age-standardized rates per 100,000 for
      the ages 40-74 were used to summarise recent geographical variations.
      Standardized rate ratios and 95% confidence intervals for the periods 1986-1990
      and 1991-1995 were compared to assess geographical variations in risk. To
      investigate changes in the magnitude of most recent trends, regression models
      fitted to the latest available 10-year period (1988-1997) were compared with
      trends in the previous decade. Fitted rates in younger (40-64) and older adults
      (65-74) in the most recent period were also compared. RESULTS: There was a great
      deal of geographical variation in the risk of mesothelioma, annual rates ranging
      from around 8 per 100,000 in Scotland, England and The Netherlands, to lower than
      1 per 100,000 in Spain (0.96), Estonia (0.85), Poland (0.85) and Yugoslavia,
      Vojvodina (0.56) among men. The rank of the rates for women was similar to that
      observed for men, although rates were considerably lower. Between 1978 and 1987,
      rates in men significantly increased in all countries (excepting Denmark). In the
      following 10 years, there was a deceleration in trend, and a significant increase
      was detectable only in England and France. In addition, the magnitude of recent
      trends in younger men was generally lower than those estimated for older men, in
      both national and regional cancer registry settings. CONCLUSIONS: While
      mesothelioma incidence rates are still rising in Europe, a deceleration has
      started in some countries. A decrease may begin in the next few years in certain
      European populations considering the deceleration of observed trends in
      mesothelioma and asbestos exposure, as well as the recent ban on its use.

PMID- 14674745
TI  - Toxicity of nucleoside analogues used to treat AIDS and the selectivity of the
      mitochondrial DNA polymerase.
AB  - Incorporation of nucleoside analogues by the mitochondrial DNA polymerase has
      been implicated as the primary cause underlying many of the toxic side effects of
      these drugs in HIV therapy. Recent success in reconstituting recombinant human
      enzyme has afforded a detailed mechanistic analysis of the reactions governing
      nucleotide selectivity of the polymerase and the proofreading exonuclease. The
      toxic side effects of nucleoside analogues are correlated with the kinetics of
      incorporation by the mitochondrial DNA polymerase, varying over 6 orders of
      magnitude in the sequence zalcitabine (ddC) > didanosine (ddI metabolized to ddA)
      > stavudine (d4T) >> lamivudine (3TC) > tenofovir (PMPA) > zidovudine (AZT) >
      abacavir (metabolized to carbovir, CBV). In this review, we summarize our current
      efforts to examine the mechanistic basis for nucleotide selectivity by the
      mitochondrial DNA polymerase and its role in mitochondrial toxicity of nucleoside
      analogues used to treat AIDS and other viral infections. We will also discuss the
      promise and underlying challenges for the development of new analogues with lower
      toxicity.

PMID- 14674746
TI  - NMR studies of the interaction of tryparedoxin with redox-inactive substrate
      homologues.
AB  - Tryparedoxins (TXNs) are trypanothione-dependent peroxiredoxin oxidoreductases
      involved in hydroperoxide detoxification that have been shown to determine
      virulence in trypanosomatids. The structure of (15)N,(13)C-doubly-labeled, C
      terminally-His-tagged tryparedoxin 1 from Crithidia fasciculata (Cf TXN1) was
      elucidated by three-dimensional NMR spectroscopy. Global folding was found to be
      similar to the crystal structure, but regions near the active site, especially
      the onset of helix alpha1 with the redox-active Cys 43 and helix alpha2 relevant
      to substrate binding, were less well defined in solution. The redox-inactive
      inhibitory substrate analogue N(1),N(8)-bis(ophthalmyl)spermidine was used to
      study the substrate/TXN interaction by two-dimensional (1)H,(15)N NMR
      spectroscopy. The NMR data complemented by molecular modeling revealed several
      alternative modes of ligand binding. The results confirm and extend the concept
      of TXN action and specificity derived from X-ray analysis and site-directed
      mutagenesis and thus improve the rational basis for inhibitor design.

PMID- 14674747
TI  - Solution structure of human saposin C: pH-dependent interaction with phospholipid
      vesicles.
AB  - Saposin C binds to membranes to activate lipid degradation in lysosomes. To get
      insights into saposin C's function, we have determined its three-dimensional
      structure by NMR and investigated its interaction with phospholipid vesicles.
      Saposin C adopts the saposin-fold common to other members of the family. In
      contrast, the electrostatic surface revealed by the NMR structure is remarkably
      different. We suggest that charge distribution in the protein surface can
      modulate membrane interaction leading to the functional diversity of this family.
      We find that the binding of saposin C to phospholipid vesicles is a pH-controlled
      reversible process. The pH dependence of this interaction is sigmoidal, with an
      apparent pK(a) for binding close to 5.3. The pK(a) values of many solvent-exposed
      Glu residues are anomalously high and close to the binding pK(a). Our NMR data
      are consistent with the absence of a conformational change prior to membrane
      binding. All this information suggests that the negatively charged electrostatic
      surface of saposin C needs to be partially neutralized to trigger membrane
      binding. We have studied the membrane-binding behavior of a mutant of saposin C
      designed to decrease the negative charge of the electrostatic surface. The
      results support our conclusion on the importance of protein surface
      neutralization in binding. Since saposin C is a lysosomal protein and pH
      gradients occur in lysosomes, we propose that lipid degradation in the lysosome
      could be switched on and off by saposin C's reversible binding to membranes.

PMID- 14674748
TI  - NMR studies of the phosphorylation motif of the HIV-1 protein Vpu bound to the F
      box protein beta-TrCP.
AB  - A protein-protein association regulated by phosphorylation of serine is examined
      by NMR studies. Degradation of the HIV receptor CD4 by the proteasome, mediated
      by the HIV-1 protein Vpu, is crucial for the release of fully infectious virions.
      Phosphorylation of Vpu at two sites, Ser52 and Ser56, on the motif DSGXXS is
      required for the interaction of Vpu with the ubiquitin ligase SCF-betaTrCP which
      triggers CD4 degradation by the proteasome. This motif is conserved in several
      signaling proteins known to be degraded by the proteasome. To elucidate the basis
      of beta-TrCP recognition, the bound conformation of the P-Vpu(41-62) peptide was
      determined by using NMR and MD. The TRNOE intensities provided distance
      constraints which were used in simulated annealing. The beta-TrCP-bound structure
      of P-Vpu was found to be similar to the structure of the free peptide in solution
      and to the structure recognized by its antibody. Residues 50-57 formed a bend
      while the phosphate groups are pointing away. The binding fragment was studied by
      STD-NMR spectroscopy. The phosphorylated motif DpS(52)GNEpS(56) was found to make
      intimate contact with beta-TrCP, and pSer52 displays the strongest binding
      effect. It is suggested that Ser phosphorylation allows protein-protein
      association by electrostatic stabilization: an obvious negative binding region of
      Vpu was recognizable by positive residues (Arg and Lys) of the WD domain of beta
      TrCP. The Ile46 residue was also found essential for interaction with the beta
      TrCP protein. Leu45 and Ile46 side chains lie in close proximity to a hydrophobic
      pocket of the WD domain.

PMID- 14674749
TI  - Crystal structure at 1.45 A resolution of alanine racemase from a pathogenic
      bacterium, Pseudomonas aeruginosa, contains both internal and external aldimine
      forms.
AB  - The structure of the catabolic alanine racemase, DadX, from the pathogenic
      bacterium Pseudomonas aeruginosa, reported here at 1.45 A resolution, is a dimer
      in which each monomer is comprised of two domains, an eight-stranded alpha/beta
      barrel containing the PLP cofactor and a second domain primarily composed of beta
      strands. The geometry of each domain is very similar to that of Bacillus
      stearothermophilus alanine racemase, but the rotation between domains differs by
      about 15 degrees. This change does not alter the structure of the active site in
      which almost all residues superimpose well with a low rms difference of 0.86 A.
      Unexpectedly, the active site of DadX contains a guest substrate that is located
      where acetate and propionate have been observed in the Bacillus structures. It is
      modeled as d-lysine and oriented such that its terminal NZ atom makes a covalent
      bond with C4' of PLP. Since the internal aldimine bond between the protein
      lysine, Lys33, and C4' of PLP is also unambiguously observed, there appears to be
      an equilibrium between both internally and externally reacted forms. The PLP
      cofactor adopts two partially occupied conformational states that resemble
      previously reported internal and external aldimine complexes.

PMID- 14674750
TI  - Unique conformer selection of human growth-regulatory lectin galectin-1 for
      ganglioside GM1 versus bacterial toxins.
AB  - Endogenous lectins induce effects on cell growth by binding to antennae of
      natural glycoconjugates. These complex carbohydrates often present more than one
      potential lectin-binding site in a single chain. Using the growth-regulatory
      interaction of the pentasaccharide of ganglioside GM(1) with homodimeric galectin
      1 on neuroblastoma cell surfaces as a model, we present a suitable strategy for
      addressing this issue. The approach combines NMR spectroscopic and computational
      methods and does not require isotope-labeled glycans. It involves conformational
      analysis of the two building blocks of the GM(1) glycan, i.e., the disaccharide
      Galbeta1-3GalNAc and the trisaccharide Neu5Acalpha2-3Galbeta1-4Glc. Their bound
      state conformations were determined by transferred nuclear Overhauser enhancement
      spectroscopy. Next, measurements on the lectin-pentasaccharide complex revealed
      differential conformer selection regarding the sialylgalactose linkage in the tri
      versus pentasaccharide (Phi and Psi value of -70 degrees and 15 degrees vs 70
      degrees and 15 degrees, respectively). To proceed in the structural analysis, the
      characteristic experimentally detected spatial vicinity of a galactose unit and
      Trp68 in the galectin's binding site offered a means, exploiting saturation
      transfer from protein to carbohydrate protons. Indeed, we detected two signals
      unambiguously assigned to the terminal Gal and the GalNAc residues. Computational
      docking and interaction energy analyses of the entire set of ligands supported
      and added to experimental results. The finding that the ganglioside's
      carbohydrate chain is subject to differential conformer selection at the
      sialylgalactose linkage by galectin-1 and GM(1)-binding cholera toxin (Phi and
      Psi values of -172 degrees and -26 degrees, respectively) is relevant for toxin
      directed drug design. In principle, our methodology can be applied in studies
      aimed at blocking galectin functionality in malignancy and beyond glycosciences.

PMID- 14674751
TI  - Mapping the binding interface of the cytochrome b5-cytochrome c complex by
      nuclear magnetic resonance.
AB  - The interaction between bovine cytochrome b(5) (cyt b(5)) and horse heart
      cytochrome c (cyt c) is investigated by NMR spectroscopy. Chemical shifts of cyt
      b(5) backbone resonances and side chain methyl resonances were monitored as a
      function of cyt c concentration. The shifts are small but saturatable and
      indicate that the binding of cyt b(5) with cyt c is in fast exchange. An
      equilibrium association constant of (6 +/- 3) x 10(4) M(-1) was obtained with a
      lower limit of 180 s(-1) for the dissociation rate of the complex. To resolve
      considerable ambiguities in the interpretation of the chemical shift mapping,
      (15)N relaxation experiments and cross-saturation experiments were used as
      alternative methods to map the cyt b(5)-cyt c binding interface. Results from the
      three experiments combined demonstrate that the conserved negatively charged
      region of cyt b(5) surrounding the solvent-exposed heme edge is involved in the
      interaction with cyt c. These data support the models proposed by Salemme and
      Mauk [(1976) J. Mol. Biol. 102, 563-568; (1993) Biochemistry 32, 6613-6623].

PMID- 14674752
TI  - Contribution of molecular modeling and site-directed mutagenesis to the
      identification of a new residue, glutamate 215, involved in the exopeptidase
      specificity of aminopeptidase A.
AB  - Aminopeptidase A is a zinc metalloenzyme that generates brain angiotensin III,
      which exerts a tonic stimulatory action on blood pressure in hypertensive
      animals. We have previously constructed a three-dimensional model of the
      ectodomain of this enzyme, using the crystal structure of leukotriene A4
      hydrolase/aminopeptidase as a template. According to this model, Glu-215, which
      is located in the active site, hydrogen bonds to the amino moiety of the
      inhibitor, 4-amino-4-phosphonobutyric acid (GluPhos), a phosphonic acid anologue
      of glutamic acid. Replacement of this residue with an aspartate or an alanine in
      the model abolished this interaction and led to a change in the position of the
      inhibitor in the active site. Mutagenic replacement of Glu-215 with an aspartate
      or an alanine drastically reduced the affinity of the recombinant enzymes for the
      substrate by a factor of 10 or 17, respectively, and the rate of hydrolysis by a
      factor of 14 or 6, respectively. Two isomers of GluPhos with different N-terminal
      amine positions differed considerably in their ability to inhibit the wild type
      (by a factor of 40), but not the mutated enzymes. These results, together with
      the interaction predicted by the model, demonstrate that Glu-215 interacts with
      the N-terminal amine of the substrate, thereby contributing, together with Glu
      352, to the determination of the exopeptidase specificity of aminopeptidase A.

PMID- 14674753
TI  - Beta-glucosylation as a part of self-resistance mechanism in
      methymycin/pikromycin producing strain Streptomyces venezuelae.
AB  - In our study of the biosynthesis of D-desosamine in Streptomyces venezuelae, we
      have cloned and sequenced the entire desosamine biosynthetic cluster. The deduced
      product of one of the genes, desR, in this cluster shows high sequence homology
      to beta-glucosidases, which catalyze the hydrolysis of the glycosidic linkages, a
      function not required for the biosynthesis of desosamine. Disruption of the desR
      gene led to the accumulation of glucosylated methymycin/neomethymycin products,
      all of which are biologically inactive. It is thus conceivable that
      methymycin/neomethymycin may be produced as inert diglycosides, and the DesR
      protein is responsible for transforming these antibiotics from their dormant to
      their active forms. This hypothesis is supported by the fact that the translated
      desR gene has a leader sequence characteristic of secretory proteins, allowing it
      to be transported through the cell membrane and hydrolyze the modified
      antibiotics extracellularly to activate them. Expression of desR and biochemical
      characterization of the purified protein confirmed the catalytic function of this
      enzyme as a beta-glycosidase capable of catalyzing the hydrolysis of glucosylated
      methymycin/neomethymycin produced by S. venezuelae. These results provide strong
      evidence substantiating glycosylation/deglycosylation as a likely self-resistance
      mechanism of S. venezuelae. However, further experiments have suggested that such
      a glycosylation/deglycosylation is only a secondary self-defense mechanism in S.
      venezuelae, whereas modification of 23S rRNA, which is the target site for
      methymycin and its derivatives, by PikR1 and PikR2 is a primary self-resistance
      mechanism. Considering that postsynthetic glycosylation is an effective means to
      control the biological activity of macrolide antibiotics, the availability of
      macrolide glycosidases, which can be used for the activation of newly formed
      antibiotics that have been deliberately deactivated by engineered
      glycosyltransferases, may be a valuable part of an overall strategy for the
      development of novel antibiotics using the combinatorial biosynthetic approach.

PMID- 14674754
TI  - Effects of length and position of an extended linker on sequence-selective DNA
      recognition of zinc finger peptides.
AB  - Engineered zinc finger proteins revealed that a linker sequence connecting zinc
      finger units has a significant effect on the DNA binding property of the protein.
      The recognition for a noncontiguous DNA target beyond the current recognition
      code of zinc finger proteins has never been determined because of the limitation
      of a zinc finger framework. DNA recognition of zinc finger proteins is limited
      only to a contiguous subset of three base pairs. We propose the recognition for a
      noncontiguous DNA target by inserting amino acids into the canonical linker
      between zinc finger units. The sequence selectivity of the new zinc finger
      peptides was evaluated by gel mobility shift assays. DNase I footprinting
      analyses clearly showed different DNA binding of various linker-extended zinc
      finger peptides. The application of a SPR measurement also revealed a DNA
      sequence selectivity of peptides. Insertion of three amino acids is enough for
      recognition of a noncontiguous DNA target with sequence selectivity. An extended
      linker will be useful for expansion of the recognition code of zinc finger
      proteins and for development of a new role for linker sequences in DNA binding of
      zinc finger proteins.

PMID- 14674755
TI  - Redox-triggered FTIR difference spectra of FAD in aqueous solution and bound to
      flavoproteins.
AB  - Flavin adenine dinucleotide (FAD) and three different flavoproteins in aqueous
      solution were subjected to redox-triggered Fourier transform infrared difference
      spectroscopy. The acquired vibrational spectra show a great number of positive
      and negative peaks, pertaining to the oxidized and reduced state of the molecule,
      respectively. Density functional theory calculations on the B3LYP/6-31G(d) level
      were employed to assign several of the observed bands to vibrational modes of the
      isoalloxazine moiety of the flavin cofactor in both its oxidized and, for the
      first time, its reduced state. Prominent modes measured for oxidized FAD include
      nu(C(4)=O) and nu(C(2)=O) at 1716 and 1674 cm(-1), respectively, nu(C(4a)=N(5))
      at 1580 cm(-1), and nu(C(10a)=N(1)) at 1548 cm(-1). Measured modes of the reduced
      form of FAD include nu(C(2)=O) at 1692 cm(-1), nu(C(4)=O) at 1634 cm(-1), and
      nu(C(4a)=C(10a)) at 1600 cm(-1). While the overall shape of the enzyme spectra is
      similar to the shape of the spectrum of free FAD, there are numerous differences
      in detail. In particular, the nu(C=N) modes of the flavin exhibit frequency
      shifts in the protein-bound form, most prominently for pyruvate oxidase where
      nu(C(10a)=N(1)) downshifts by 14 cm(-1) to 1534 cm(-1). The significance of this
      shift and a possible explanation in connection with the bent conformation of the
      flavin cofactor in this enzyme are discussed.

PMID- 14674756
TI  - Infrared studies of carbon monoxide binding to carbon monoxide
      dehydrogenase/acetyl-CoA synthase from Moorella thermoacetica.
AB  - Carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS) is a bifunctional
      enzyme that catalyzes the reversible reduction of carbon dioxide into carbon
      monoxide and the coupled synthesis of acetyl-CoA from the carbon monoxide
      produced. Exposure of CODH/ACS from Moorella thermoacetica to carbon monoxide
      gives rise to several infrared bands in the 2100-1900 cm(-1) spectral region that
      are attributed to the formation of metal-coordinated carbon monoxide species.
      Infrared bands attributable to M-CO are not detected in the as-isolated enzyme,
      suggesting that the enzyme does not contain intrinsic metal-coordinated CO
      ligands. A band detected at 1996 cm(-1) in the CO-flushed enzyme is assigned as
      arising from CO binding to a metal center in cluster A of the ACS subunit. The
      frequency of this band is most consistent with it arising from a terminally
      coordinated Ni(I) carbonyl. Multiple infrared bands at 2078, 2044, 1970, 1959,
      and 1901 cm(-1) are attributed to CO binding at cluster C of the CODH subunit.
      All infrared bands attributed to metal carbonyls decay in a time-dependent
      fashion as CO(2) appears in the solution. These observations are consistent with
      the enzyme-catalyzed oxidation of carbon monoxide until it is completely depleted
      from solution during the course of the experiments.

PMID- 14674757
TI  - Persistent conformational heterogeneity of triosephosphate isomerase: separation
      and characterization of conformational isomers in solution.
AB  - Subunit dissociation of dimeric rabbit muscle triosephosphate isomerase (TIM) by
      hydrostatic pressure has previously been shown not to follow the expected
      dependence on protein concentration [Rietveld and Ferreira (1996) Biochemistry
      35, 7743-7751]. This anomalous behavior was attributed to persistent
      conformational heterogeneity (i.e., the coexistence of long-lived conformational
      isomers) in the ensemble of TIM dimers. Here, we initially show that subunit
      dissociation/unfolding of TIM by guanidine hydrochloride (GdnHCl) also exhibits
      an anomalous dependence on protein concentration. Dissociation/unfolding of TIM
      by GdnHCl was investigated by intrinsic fluorescence and circular dichroism
      spectroscopies and was found to be a highly cooperative transition in which the
      tertiary and secondary structures of the protein were concomitantly lost. A
      procedure based on size-exclusion chromatography in the presence of intermediate
      (0.6 M) GdnHCl concentrations was developed to isolate two conformational isomers
      of TIM that exhibit significantly different stabilities and kinetics of unfolding
      by GdnHCl. Complete unfolding of the two isolated conformers at a high GdnHCl
      concentration (1.5 M), followed by refolding by removal of the denaturant,
      completely abolished the differences in their unfolding kinetics. These results
      indicate that such differences stem from conformational heterogeneity of TIM and
      are not related to any chemical modification of the protein. Furthermore, they
      add support to the notion that long-lived conformational isomers of TIM coexist
      in solution and provide a basis for the interpretation of the persistent
      heterogeneity of this protein.

PMID- 14674758
TI  - Properties of short-chain dehydrogenase/reductase RalR1: characterization of
      purified enzyme, its orientation in the microsomal membrane, and distribution in
      human tissues and cell lines.
AB  - Recently, we reported the first biochemical characterization of a novel member of
      the short-chain dehydrogenase/reductase superfamily, retinal reductase 1 (RalR1)
      (Kedishvili et al. (2002) J. Biol. Chem. 277, 28909-28915). In the present study,
      we purified the recombinant enzyme from the microsomal membranes of insect Sf9
      cells, determined its catalytic efficiency for the reduction of retinal and the
      oxidation of retinol, established its transmembrane topology, and examined the
      distribution of RalR1 in human tissues and cell lines. Purified RalR1-His(6)
      exhibited the apparent K(m) values for all-trans-retinal and all-trans-retinol of
      0.12 and 0.6 microM, respectively. The catalytic efficiency (k(cat)/K(m)) for the
      reduction of all-trans-retinal (150,000 min(-1) mM(-1)) was 8-fold higher than
      that for the oxidation of all-trans-retinol (18,000 min(-1) mM(-1)). Protease
      protection assays and site-directed mutagenesis suggested that the enzyme is
      anchored in the membrane by the N-terminal signal-anchor domain, with the
      majority of the polypeptide chain located on the cytosolic side of the membrane.
      An important feature that prevented the translocation of RalR1 across the
      membrane was the positively charged R(25)K motif flanking the N-terminal signal
      anchor. The cytosolic orientation of RalR1 suggested that, in intact cells, the
      enzyme would function predominantly as a reductase. Western blot analysis
      revealed that RalR1 is expressed in a wide variety of normal human tissues and
      cancer cell lines. The expression pattern and the high catalytic efficiency of
      RalR1 are consistent with the hypothesis that RalR1 contributes to the reduction
      of retinal in various human tissues.

PMID- 14674759
TI  - Redox-dependent modulation of aconitase activity in intact mitochondria.
AB  - It has previously been reported that exposure of purified mitochondrial or
      cytoplasmic aconitase to superoxide (O(2)(-)(*) or hydrogen peroxide (H(2)O(2))
      leads to release of the Fe-alpha from the enzyme's [4Fe-4S](2+) cluster and to
      inactivation. Nevertheless, little is known regarding the response of aconitase
      to pro-oxidants within intact mitochondria. In the present study, we provide
      evidence that aconitase is rapidly inactivated and subsequently reactivated when
      isolated cardiac mitochondria are treated with H(2)O(2). Reactivation of the
      enzyme is dependent on the presence of the enzyme's substrate, citrate. EPR
      spectroscopic analysis indicates that enzyme inactivation precedes release of the
      labile Fe-alpha from the enzyme's [4Fe-4S](2+) cluster. In addition, as judged by
      isoelectric focusing gel electrophoresis, the relative level of Fe-alpha release
      and cluster disassembly does not reflect the magnitude of enzyme inactivation.
      These observations suggest that some form of posttranslational modification of
      aconitase other than release of iron is responsible for enzyme inactivation. In
      support of this conclusion, H(2)O(2) does not exert its inhibitory effects by
      acting directly on the enzyme, rather inactivation appears to result from
      interaction(s) between aconitase and a mitochondrial membrane component
      responsive to H(2)O(2). Nevertheless, prolonged exposure of mitochondria to
      steady-state levels of H(2)O(2) or O(2)(-)(*) results in disassembly of the [4Fe
      4S](2+) cluster, carbonylation, and protein degradation. Thus, depending on the
      pro-oxidant species, the level and duration of the oxidative stress, and the
      metabolic state of the mitochondria, aconitase may undergo reversible modulation
      in activity or progress to [4Fe-4S](2+) cluster disassembly and proteolytic
      degradation.

PMID- 14674760
TI  - Time-resolved resonance Raman and time-resolved step-scan FTIR studies of nitric
      oxide reductase from Paracoccus denitrificans: comparison of the heme b3-FeB site
      to that of the heme-CuB in oxidases.
AB  - Time-resolved resonance Raman (TR(3)) and time-resolved step-scan (TRS(2)) FTIR
      spectroscopies have been used to probe the structural dynamics at the heme b(3)
      proximal and distal sites after carbon monoxide photolysis from fully reduced CO
      bound nitric oxide reductase. The Raman spectra of the transient species exhibit
      structural differences relative to the equilibrium geometry of heme b(3). The
      most significant of these is a shift of 8 cm(-1) to higher frequency of the 207
      cm(-1) mode, and a shift of 7 cm(-1) to lower frequency of the nu(4) mode. Our
      results indicate that the 207 cm(-1) mode observed in the equilibrium-reduced
      heme b(3) originates from nu(Fe-His). Its behavior in the photolytic transients
      indicates that the relaxed Fe-His state is not significantly populated. We
      suggest that relaxation along the tilt angle (theta) of the proximal histidine
      with respect to the heme plane and the out-of-plane displacement of the Fe (q)
      are coupled, and ligand binding and dissociation are accompanied by significant
      changes in the angular orientation of the His ligand. The results are compared to
      those obtained for the aa(3)-cytochrome c oxidase from Paracoccus denitrificans.
      The results are compared to those obtained for the aa(3)-cytochrome c oxidase
      from P. denitrificans. The TR(3) and TRS(2) FTIR data demonstrate significant
      alterations in the nature of the heme-protein dynamics between nitric oxide
      reductase and heme-copper oxidases resulting from specific structural differences
      in their respective hemepockets.

PMID- 14674761
TI  - The 33 kDa protein of photosystem II is a low-affinity calcium- and lanthanide
      binding protein.
AB  - We have shown that the isolated 33 kDa protein of photosystem II contains one
      calcium and one lanthanide low-affinity binding site with binding constants
      (K(D)) on the order of 10(-5) M. Binding of calcium or lanthanides to this site
      induces conformational changes in the protein that manifest in fluorescence
      emission spectra of the protein, circular dichroism spectra, and calorimetric
      thermograms where the phase transitions are shifted to lower temperatures. The
      role of calcium binding to the 33 kDa protein in the attainment of its native
      structure and the significance of this interaction for the oxygen evolution
      process are discussed.

PMID- 14674762
TI  - Phosphorylation-dephosphorylation of light-harvesting complex II as a response to
      variation in irradiance is thiol sensitive and thylakoid sufficient: modulation
      of the sensitivity of the phenomenon by a peripheral component.
AB  - Downregulation of phosphorylation of chlorophyll a/b-binding proteins (LHCII) of
      the photosystem II at high irradiance could only be demonstrated with leaf discs
      but not in isolated thylakoids. The present view suggests this phenomenon to be
      regulated by stromal thioredoxin. Here, we show that high-light inactivation of
      LHCII phosphorylation can be reproduced in isolated thylakoids and have explained
      the apparent absence of inactivation in vitro to be due to the derepressed
      activity of a peripheral kinase. We investigated this phenomenon with Arachis
      hypogea thylakoids prepared with (Th:A) or without (Th:B) tricine, where tricine
      is known for removing peripheral proteins from thylakoids. While LHCII remained
      phosphorylated at high irradiance in Th:B, the response of Th:A mimicked Arachis
      leaflets where LHCII was transiently phosphorylated with irradiance. LHCII
      phosphorylation in Th:A was sensitive to thiol reducing conditions, but in Th:B,
      the phenomenon became insensitive to thiol reduction following illumination.
      Washing Th:B with tricine made them resemble Th:A, and conversely, Th:A
      reconstituted with the Tricine extract resembled Th:B with respect to both
      irradiance response and thiol sensitivity. In vitro phosphorylation reactions
      indicated a thiol insensitive kinase activity to be present in the Tricine
      extract that was capable of phosphorylating histone H1 as well as purified LHCII.
      This peripherally associated kinase activity explained the sustenance of LHCII
      phosphorylation as well as its thiol insensitivity at high irradiance in Th:B
      thylakoids. Contrary to the current view, our results clearly show that
      irradiance dependent phosphorylation and dephosphorylation of LHCII is a
      thylakoid sufficient phenomenon, although it remained open to regulation by thiol
      redox state modulation.

PMID- 14674763
TI  - Effect of pH on the oxidation-reduction properties of thioredoxins.
AB  - Oxidation-reduction midpoint potential (E(m)) versus pH profiles were measured
      for wild-type thioredoxins from Escherichia coli and from the green alga
      Chlamydomonas reinhardtii and for a number of site-directed mutants of these two
      thioredoxins. These profiles all exhibit slopes of approximately -59 mV per pH
      unit, characteristic of the uptake of two protons per reduction of an active-site
      thioredoxin disulfide, at acidic, neutral, and moderately alkaline pH values. At
      higher pH values, these profiles exhibit slopes of either -29.5 mV per pH unit,
      characteristic of the uptake of one proton per disulfide reduced, or are pH
      independent, indicating that neither proton uptake nor proton release is
      associated with reduction of the active-site disulfide. Reduction of the two wild
      type thioredoxins is accompanied by the uptake of two protons even at pH values
      where the more acidic cysteine thiol group of the reduced proteins would be
      expected to be completely unprotonated. The effect of site-directed mutagenesis
      of two highly conserved aspartate residues that play important structural and/or
      catalytic roles in both thioredoxins, and which could in principle play a role in
      proton transfer, on the pK(a) values of redox-linked acid dissociations (deduced
      from changes in slope of the E(m) versus pH profiles) has also been determined
      for both E. coli thioredoxin and C. reinhardtii thioredoxin h.

PMID- 14674764
TI  - Disease-causing SAP mutants are defective in ligand binding and protein folding.
AB  - The X-linked lymphoproliferative (XLP) syndrome is caused by mutations or
      deletions in the SH2D1A gene that encodes an SH2 domain protein named SH2D1A or
      SAP. The identification of a number of missense mutations within the protein's
      SH2 domain, each of which can directly cause disease, provides a unique
      opportunity to investigate the function of an interaction protein module, SH2, in
      the pathogenesis of XLP. We show here that SAP mutants found in XLP patients are
      defective in binding its physiological ligands signaling lymphocyte activating
      molecule (SLAM), a co-receptor in T cell activation, and Fyn, a Src family
      protein tyrosine kinase. Consequently, these mutants are deficient in signaling
      through the SLAM receptor. This is reflected by compromised abilities for the
      mutants to recruit Fyn to SLAM and to activate Fyn, by reduced phosphorylation of
      the receptor, and by deficiencies for the mutants in blocking binding of SHP-2 to
      SLAM. Furthermore, all mutants examined are defective in protein folding as
      manifested by their significantly reduced melting temperatures upon thermal
      denaturation, compared to that of SAP. Taken together, these results suggest that
      defects in ligand binding, receptor signaling, and protein folding collectively
      contribute to the loss of function for disease-causing SAP mutants.

PMID- 14674765
TI  - The chaperoning properties of mouse grp170, a member of the third family of hsp70
      related proteins.
AB  - The 170 kDa glucose-regulated protein (grp170) is an endoplasmic reticulum
      resident protein that shares some sequence homology with both the hsp70 and
      hsp110 heat shock protein (hsp) families, yet is representative of a third and
      unique family of stress proteins. Despite observations indicating important roles
      in normal cellular functions, the in vitro chaperone properties of grp170 have
      not been rigorously examined. We have cloned mouse grp170 and expressed the
      recombinant protein in a baculovirus expression system. The function of
      recombinant grp170 was then assessed by determining its ability to bind to and
      prevent aggregation of heat-denatured luciferase. Grp170 maintains heat-denatured
      luciferase in a soluble state in the absence of ATP. In the presence of rabbit
      reticulocyte lysate, grp170 can refold and partially restore function to
      denatured luciferase. The chaperoning function of grp170 was also studied using
      domain deletion mutants, designed using the crystal structure of DnaK and the
      theoretical secondary structure of hsp110 as guides. Unlike hsp70 and hsp110,
      grp170 appears to have two domains capable of binding denatured luciferase and
      inhibiting its heat-induced aggregation. The two domains were identified as being
      similar to the classical beta-sandwich peptide binding domain and the C-terminal
      alpha-helical domain in hsp70 and hsp110. The ability of the C-terminal region to
      bind peptides is a unique feature of grp170.

PMID- 14674766
TI  - Characterization of Saccharomyces cerevisiae Ras1p and chimaeric constructs of
      Ras proteins reveals the hypervariable region and farnesylation as critical
      elements in the adenylyl cyclase signaling pathway.
AB  - Ras1p and Ras2p, from Saccharomyces cerevisiae, are GTP-binding proteins that are
      essential elements in the signaling cascade leading to the activation of adenylyl
      cyclase. To overcome proteolytic activities that have hampered biochemical
      studies of Ras1p so far, its gene was genetically modified after which full
      length Ras1p could be obtained. The interaction of farnesylated and unprenylated
      Ras1p with guanine nucleotides, guanine nucleotide exchange factors, GTPase
      activating proteins, and adenylyl cyclase was compared to Ras2p and human Ha-Ras
      interactions. Farnesylation of Ras proteins was demonstrated to be a prerequisite
      for membrane-bound guanine nucleotide exchange factor dependent formation of Ras
      GTP complexes, and for efficient Ras-mediated adenylyl cyclase activation. To
      relate observed functional deviations with sequence differences between Ras1p and
      Ras2p, which reside almost exclusively within the hypervariable region, truncated
      versions and chimaeras of the Ras proteins were made. The characteristics of
      these constructs point to the presence of the hypervariable region of yeast Ras
      proteins for an efficient activation of adenylyl cyclase. The importance of the
      latter was confirmed as inhibition of the activation of adenylyl cyclase by an
      isolated farnesylated hypervariable region of Ras2p could be shown. This strongly
      suggests that the hypervariable region of Ras proteins can interact directly with
      adenylyl cyclase.

PMID- 14674767
TI  - Structural organization of the receptor associated protein.
AB  - The receptor associated protein (RAP) is a 38 kDa ER-resident protein that binds
      tightly to the low density lipoprotein receptor-related protein (LRP), and other
      members of the LDL receptor family of receptors, and competes with all known LRP
      ligands for binding to LRP. To better understand the domain structure and
      organization of RAP, we have expressed RAP subfragments and examined them by two
      dimensional HSQC NMR and fluorescence spectroscopies, by differential scanning
      calorimetry, and by both equilibrium and velocity sedimentation measurements. We
      found that the protein is organized into three domains located in the first third
      (1D), middle third (2D), and last third (3D) of the protein. All three domains
      adopt stable tertiary structure as isolated domains and are monomers. Whereas
      domains 1D and 2D do not interact with one another, 3D interacts with 2D, both in
      a 2D-3D construct and in intact RAP. Sedimentation measurements also indicated
      that intact RAP, although monomeric, is significantly elongated.

PMID- 14674768
TI  - Molecular logic of 11-cis-retinoid biosynthesis in a cone-dominated species.
AB  - The biochemical pathway to visual chromophore biosynthesis in rod-dominated
      animals involves minimally a two component system in which all-trans-retinyl
      esters, generated by the action of lecithin retinol acyltransferase (LRAT) on
      vitamin A, are processed into 11-cis-retinol by isomerohydrolase. Possible
      differences in retinoid metabolism in cone-dominated animals have been noted in
      the literature, so it was of interest to explore whether these differences are
      tangential or fundamental. Central to this issue is whether cone-dominated
      animals use an isomerohydrolase (IMH)-based mechanism in the predominant pathway
      to 11-cis-retinoids. Here, it is shown that all-trans-retinyl esters (tREs) are
      the direct precursors of 11-cis-retinol formation in chicken retinyl pigment
      epithelium/retina preparations. This conclusion is based on at least three
      avenues of evidence. First, reagents that block tRE synthesis from vitamin A also
      block 11-cis-retinol synthesis. Second, pulse-chase experiments also establish
      that tREs are the precursors to 11-cis-retinol. Finally, 11-cis-retinyl
      bromoacetate, a known affinity-labeling agent of isomerohydrolase, also blocks
      chromophore biosynthesis in the cone system.

PMID- 14674769
TI  - Modification of the proteolytic fragmentation pattern upon oxidation of cysteines
      from ribulose 1,5-bisphosphate carboxylase/oxygenase.
AB  - The proteolytic susceptibility of the native CO(2)-fixing photosynthetic enzyme
      ribulose 1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39, Rubisco) has been
      shown to increase in vitro after oxidative treatments that affect cysteine
      thiols. A limited incubation of oxidized (pretreated with the disulfide
      cystamine) Rubisco from Chlamydomonas reinhardtii with subtilisin or proteinase K
      generated fragments of molecular mass about 53 kDa (band I in SDS-PAGE) and 47
      kDa (band II) derived from the large subunit (55 kDa) of the enzyme. In contrast,
      proteolysis of the reduced Rubisco (pretreated with the free thiol cysteamine)
      produced only the 53 kDa band. The same fragmentation pattern was reproduced with
      Rubiscos from other algae and higher plants, as well as with other chemical
      modifications of protein cysteines. N-terminal sequencing of the fragments showed
      that band I arised from clipping the unstructured N-terminal stretch of the large
      subunit up to Lys18. Band II was generated by a cleavage close to Val69. The
      increased susceptibility of the oxidized form resulted from proteases gaining
      access to a loop (from Ser61 to Thr68) located between stretches of secondary
      structure that form the N-terminal domain. Native electrophoresis and kinetic
      analysis of fragment accumulation during subtilisin digestion demonstrated that
      subunit dissociation was induced by the proteolytic processing at the Ser61-Thr68
      loop, which is characteristic of the oxidized Rubisco. Holoenzyme dissasembly was
      readily followed by the full degradation of the released subunits. In contrast,
      the limited processing to band I observed with the reduced enzyme did not
      compromise the quaternary structure of the Rubisco hexadecamer, thus preventing
      further proteolysis.

PMID- 14674770
TI  - Importance of the prime subsites of the C1s protease of the classical complement
      pathway for recognition of substrates.
AB  - The classical complement pathway, which plays a vital role in preventing
      infection, is initiated by the action of the serine proteases C1r and C1s. We
      have examined the hydrolysis of substrates representing cleavage sequences in the
      physiological substrates for C1s, C2 and C4. These studies showed that the P(1)'
      P(4)' substrate residues of C2 and C4 conferred greater affinity of substrate for
      enzyme and also induced a sigmoidal dependence of enzyme velocity on substrate
      concentration. This indicates that the substrate gave rise to homotropic positive
      cooperative behavior in the enzyme. When C1s was in complex with C1q and C1r, as
      would occur under physiological conditions, the same behavior was observed,
      indicating that this mechanism is relevant in the complement pathway in vivo. We
      further investigated the requirements of C1s for prime side amino acids by
      examining a substrate library in which each of the P(1)'-P(4)' positions had been
      substituted by different classes of amino acids. This revealed that the P(1)'
      position was a major determinant of the selectivity of the enzyme, while certain
      substitutions at the P(1)'-P(4)' positions abolished the allosteric behavior,
      indicating that contact residues at these positions in the C1s enzyme must
      mediate the cooperativity. The studies reported here highlight the importance of
      prime subsites in C1s for interaction with its cognate substrates in the
      complement pathway and therefore yield greater understanding of the mechanism of
      interaction between this vital protease and its physiological substrates.

PMID- 14674771
TI  - Bestowing antifungal and antibacterial activities by lipophilic acid conjugation
      to D,L-amino acid-containing antimicrobial peptides: a plausible mode of action.
AB  - The dramatically increased frequency of opportunistic fungal infections has
      prompted research to diversify the arsenal of antifungal agents. Antimicrobial
      peptides constitute a promising family for future antibiotics with a new mode of
      action. However, only a few are effective against fungal pathogens because of
      their ability to self-assemble. Recently, we showed that the conjugation of fatty
      acids to the potent antibacterial peptide magainin endowed it with antifungal
      activity concomitant with an increase in its oligomeric state in solution. To
      investigate whether a high potency of the parental peptide is prerequisite for
      antifungal activity, we conjugated undecanoic acid (UA) and palmitic acid (PA) to
      inactive diastereomers of magainin containing four d-amino acids ([D]-4
      magainin), as well as to a weakly active diastereomeric lytic peptide containing
      Lys and Leu ([D]-K(5)L(7)). All lipopeptides gained potent activity toward
      Cryptococcus neoformans. Most importantly, [D]-K(5)L(7)-UA was highly potent
      against all microorganisms tested, including bacteria, yeast, and opportunistic
      fungi. All lipopeptides increased the permeability of Escherichia coli
      spheroplasts and intact C. neoformans, as well as their corresponding membranes,
      phosphatidylethanol (PE)/phosphatidylglycerol (PG) and phosphatidylcholine
      (PC)/PE/phosphatidylinositol (PI)/ergosterol, respectively. The extent of
      membrane-permeating activity correlated with their biological function,
      suggesting that the plasma membrane was one of their major targets. Circular
      dichroism (CD) and attenuated total reflectance Fourier transform infrared (ATR
      FTIR) spectroscopy revealed that their mode of oligomerization in solution,
      structure, and organization in membranes have important roles regarding their
      antibacterial and antifungal activities. Together with the advantage of using
      diastereomers versus all l-amino acid peptides, this study paves the way to the
      design of a new group of potent antifungal peptides urgently needed to combat
      opportunistic fungal infection.

PMID- 14674772
TI  - Differential modes of recognition in N peptide-boxB complexes.
AB  - N proteins from bacteriophages lambda, P22, and phi21 modulate transcription
      elongation by binding nascent "boxB" mRNA hairpins. This RNA recognition is
      mediated by N-terminal arginine-rich peptide sequences capable of interacting
      with their cognate boxB RNA targets. Here, we have analyzed the affinity and
      specificity of the peptide-RNA interactions that modulate this transcriptional
      switch. To do this, we constructed a series of peptides based on the wild-type
      lambda, P22, and phi21 N protein binding domains ranging from 11 to 22 residues
      and analyzed their interactions with the leftward and rightward boxB RNA hairpin
      targets for all three phage. Binding constant (K(d)) values were determined using
      RNA hairpins labeled with 2-aminopurine (2AP) and monitoring the fluorescence
      change as peptide was added. K(d)'s demonstrate that lambda and P22 N peptides
      bind to their cognate boxB targets with high specificity and show equal
      affinities for their leftward and rightward hairpins. Surprisingly, phi21 shows
      very little specificity for its cognate targets. Lambda and P22 N peptides
      exhibit differential modes of recognition with specificity conferred by their
      amino- and carboxy-terminal modules, respectively. We have generated a reciprocal
      matrix of substituted peptides to examine the contributions of individual
      residues to specificity. Amino acid coupling analysis supports a binding model
      where the Arg8 residue of lambda peptide acts as a conformational hot spot,
      anchoring the induced loop fold of its boxB hairpin target.

PMID- 14674773
TI  - Distinct domain functions regulating de novo DNA synthesis of thermostable DNA
      primase from hyperthermophile Pyrococcus horikoshii.
AB  - DNA primases are essential components of the DNA replication apparatus in every
      organism. Reported here are the biochemical characteristics of a thermostable DNA
      primase from the thermophilic archaeon Pyrococcus horikoshii, which formed the
      oligomeric unit L(1)S(1) and synthesized long DNA primers 10 times more
      effectively than RNA primers. The N-terminal (25KL) and C-terminal halves (20KL)
      of the large subunit (L) play distinct roles in regulating de novo DNA synthesis
      of the small catalytic subunit (S). The 25KL domain has a dual function. One
      function is to depress the large affinity of the intrasubunit domain 20KL for the
      template DNA until complex (L(1)S(1) unit) formation. The other function is to
      tether the L subunit tightly to the S subunit, probably to promote effective
      interaction between the intrasubunit domain 20KL and the active center of the S
      subunit. The 20KL domain is a central factor to enhance the de novo DNA synthesis
      activity of the catalytic S subunit since the total affinity of the L(1)S(1) unit
      is mainly derived from the affinity of 20KL, which is elevated more than 10 times
      by the heterodimer formation, presumably due to the cancellation of the
      inhibitory activity of 25KL through tight binding to the S subunit.

PMID- 14674775
TI  - Structure of triglyceride-rich human low-density lipoproteins according to
      cryoelectron microscopy.
AB  - Low-density lipoprotein (LDL) particles from normolipidemic individuals contain a
      cholesteryl ester-rich core that undergoes a thermal transition from a liquid
      crystalline to an isotropic liquid phase between 20 and 35 degrees C. LDL from
      hypertriglyceridemic patients or prepared in vitro by the exchange of very low
      density lipoprotein for LDL cholesteryl esters is triglyceride-rich, does not
      have a thermal transition above 0 degrees C, and exhibits impaired binding to the
      LDL receptor on normal human skin fibroblasts. Cryoelectron microscopy of LDL
      quick-frozen from 10 (core-frozen) and 40 degrees C (core-melted) revealed
      ellipsoidal particles with internal striations and round particles devoid of
      striations, respectively. Cryoelectron microscopy of triglyceride-rich LDL
      prepared in vitro revealed particles similar to the core-melted normolipidemic
      LDL, i.e., round particles without striations. These data suggest that the LDL
      core in the liquid crystalline phase is characterized by the appearance of
      striations, whereas LDL with a core that is an isotropic liquid lacks striations.
      It is suggested that freezing the LDL core into a liquid crystalline phase
      imposes structural constraints that force LDL from a sphere without partitions to
      an ellipsoid with partitions. We further suggest that the striation-defined
      lamellae are a structural feature of a liquid crystalline neutral lipid core that
      is a determinant of normal binding to the LDL receptor and that conversion of the
      neutral lipid core of LDL to the isotropic liquid phase via an increase in the
      temperature or via the addition of triglyceride partially ablates the receptor
      binding determinants on the LDL surface. This effect is likely achieved through
      changes in the conformation of apo-B-100. These data suggest that the physical
      state of the LDL core determines particle shape, surface structure, and metabolic
      fate.

PMID- 14674774
TI  - Free-energy landscapes of ion-channel gating are malleable: changes in the number
      of bound ligands are accompanied by changes in the location of the transition
      state in acetylcholine-receptor channels.
AB  - Acetylcholine-receptor channels (AChRs) are allosteric membrane proteins that
      mediate synaptic transmission by alternatively opening and closing ("gating") a
      cation-selective transmembrane pore. Although ligand binding is not required for
      the channel to open, the binding of agonists (for example, acetylcholine)
      increases the closed right harpoon over left harpoon open equilibrium constant
      because the ion-impermeable --> ion-permeable transition of the ion pathway is
      accompanied by a low-affinity --> high-affinity change at the agonist-binding
      sites. The fact that the gating conformational change of muscle AChRs can be
      kinetically modeled as a two-state reaction has paved the way to the experimental
      characterization of the corresponding transition state, which represents a
      snapshot of the continuous sequence of molecular events separating the closed and
      open states. Previous studies of fully (di) liganded AChRs, combining single
      channel kinetic measurements, site-directed mutagenesis, and data analysis in the
      framework of the linear free-energy relationships of physical organic chemistry,
      have suggested a transition-state structure that is consistent with channel
      opening being an asynchronous conformational change that starts at the
      extracellular agonist-binding sites and propagates toward the intracellular end
      of the pore. In this paper, I characterize the gating transition state of
      unliganded AChRs, and report a remarkable difference: unlike that of diliganded
      gating, the unliganded transition state is not a hybrid of the closed- and open
      state structures but, rather, is almost indistinguishable from the open state
      itself. This displacement of the transition state along the reaction coordinate
      obscures the mechanism underlying the unliganded closed right harpoon over left
      harpoon open reaction but brings to light the malleable nature of free-energy
      landscapes of ion-channel gating.

PMID- 14674776
TI  - Fluorescence based structural analysis of tryptophan analogue-AMP formation in
      single tryptophan mutants of Bacillus stearothermophilus tryptophanyl-tRNA
      synthetase.
AB  - The symmetrical dimer structure of tryptophanyl-tRNA synthetase is similar to
      that of tyrosyl-tRNA synthetase whose binding behavior and structural details
      have been elucidated in detail. The structure of both subunits after forming the
      intermediate tryptophanyl-AMP has important implications for the binding of the
      cognate tRNA(Trp). Single tryptophan mutants of Bacillus stearothermophilus
      tryptophanyl-tRNA synthetase have been constructed and expressed and used to
      probe structural changes in different domains of the enzyme in both subunits.
      Substrate titrations using the Trp analogues 4-fluorotryptophan and 7
      azatryptophan in the presence of ATP to form the corresponding aminoacyl
      adenylate reveal significant structural changes occurring throughout the active
      subunit in regions not confined to the active site. Changes in environment around
      the specific Trp residues were monitored using UV absorbance and steady-state
      fluorescence measurements. When titrated with 4-fluorotryptophan, both Trp 91 and
      Trp 290 fluorescence is quenched (49 and 22%, respectively) when one subunit has
      formed Trp-AMP. The fluorescence of Trp 48 is enhanced 19%. No further change in
      signal was observed after a 1:1 dimer/L-4FW-AMP complex ratio had been
      established. Using an anion-exchange filter binding assay with radiolabeled l-Trp
      as a substrate, binding to only one subunit was observed under nonsaturating
      conditions. This agrees with the results of the assay using 7-azatryptophan as a
      substrate. The observed changes extend to the unfilled subunit where a similar
      structure is believed to form after one subunit has formed tryptophan-AMP.
      Movement in the regions of the enzyme containing Trp 290 and Trp 91 suggests a
      mechanism for cross-subunit communication involving the helical backbone and
      dimer interface containing these two residues.

PMID- 14674777
TI  - X-ray absorption spectroscopic analysis of reductive [2Fe-2S] cluster degradation
      in hyperthermophilic archaeal succinate:caldariellaquinone oxidoreductase
      subunits.
AB  - The biological [2Fe-2S] clusters play important roles in electron transfer and
      cellular signaling for a variety of organisms from archaea, bacteria to eukarya.
      The two recombinant hyperthermophilic archaeal [2Fe-2S] cluster-binding proteins,
      SdhC and the N-terminal domain fragment of SdhB, of Sulfolobus tokodaii
      respiratory complex II overproduced in Escherichia coli are thermostable as
      isolated, but moderately sensitive to reduction with excess dithionite. We used
      iron K-edge X-ray absorption spectroscopy to monitor the structural changes of
      their Fe sites in the irreversible [2Fe-2S] cluster degradation process.
      Regardless of the differences in the cluster-ligating cysteine motifs and the XAS
      detectable [2Fe-2S](2+) cluster environments, a complete reductive breakdown of
      the [2Fe-2S] clusters resulted in the appearance of a new Fourier transform (FT)
      peak at approximately 3.3 A with a concomitant loss of the Fe-Fe interaction at
      ca. 2.7 A for both proteins. On the basis of the unambiguous assignment of the
      3.3 A FT peak, our results suggest that a biological [2Fe-2S] cluster breakdown
      under reducing conditions generally releases Fe(2+) from the polypeptide chain
      into the aqueous solution, and the Fe(2+) might then be recruited as a secondary
      ferrous iron source for de novo biosynthesis and/or regulation of iron-binding
      enzymes in the cellular system.

PMID- 14674778
TI  - Scientific basis for process and catalyst design in the selective oxidation of
      methane to formaldehyde.
AB  - The mechanism and kinetics of the gas-phase selective oxidation of methane to
      formaldehyde (MPO) are revised in the general context of catalytic oxidations. In
      agreement with ab initio calculations of the energy barrier for the activation of
      methane on transition metal oxide complexes, a formal Langmuir-Hinshelwood
      kinetic model is proposed which accounts for the "steady-state" conditions and
      activity-selectivity pattern of MPO catalysts, providing an original support to
      process design and catalyst development.

PMID- 14674779
TI  - Femtosecond absorption spectroscopy of transition metal charge-transfer
      complexes.
AB  - Our research is concerned with the application of femtosecond time-resolved
      absorption techniques to the study of the photophysics of transition metal
      complexes. The focus is to understand the events that characterize the process of
      excited-state evolution from the time a photon is absorbed by a molecule to the
      formation of the lowest-energy excited state of the system. This Account
      describes our initial observations in this area and includes examples detailing
      these dynamics as they occur in the charge-transfer excited states of transition
      metal polypyridyl chromophores.

PMID- 14674780
TI  - Chromophore-functionalized gold nanoparticles.
AB  - We report in this Account the design of chromophore-functionalized metal
      nanoparticles and the detailed investigation of the ground- and excited-state
      interactions between the metal nanoparticles and the photoactive molecules. The
      methodologies adopted for organizing chromophore-functionalized gold
      nanoparticles on two-dimensional surfaces and the mechanistic details of various
      deactivation channels of the photoexcited chromophores, such as energy and
      electron transfer to the metal nanoparticle, are presented. The possible
      applications of such chromophore-functionalized gold nanoparticles in
      photovoltaics, light-mediated binding and release of biologically important
      molecules such as amino acid derivatives, and fluorescent display devices are
      described.

PMID- 14674781
TI  - Strategies for heterocyclic construction via novel multicomponent reactions based
      on isocyanides and nucleophilic carbenes.
AB  - This Account focuses mainly on our recent endeavors in the area of multicomponent
      reactions (MCRs) involving zwitterionic species generated by the addition of
      isocyanides and nucleophilic carbenes such as dimethoxycarbene and N-heterocyclic
      carbenes to activated alkynes. The strategy employed encompasses the interception
      of 1:1 zwitterionic species, generated in situ with a wide range of
      electrophiles. The new MCRs developed offer an efficient and convenient entry
      into several heterocycles of biological and synthetic importance.

PMID- 14674782
TI  - Asymmetric catalytic hydrogenation. Design of new Ru catalysts and chiral
      ligands: from laboratory to industrial applications.
AB  - This Account covers the design of Ru catalysts and ligands. Two classes of chiral
      phosphine ligands are prepared: the electron-rich trans-2,4-substituted
      phosphetanes, readily available from optically pure 1,3-diol cyclic sulfates, and
      atropoisomeric ligands (SYNPHOS, MeO-NAPhePHOS, bearing heterotopic biaryl
      moieties, and a chiral water-soluble diguanidinium binaphthyl diphosphine, Digm
      BINAP). Applications of these ligands to rhodium- and ruthenium-mediated
      hydrogenation of ketones and olefins have been reported with high
      enantioselectivities. The recognition abilities of Ru-SYNPHOS for a wide range of
      ketones is superior to those observed with BINAP, MeO-NAPhePHOS, and MeO-BIPHEP.
      Several biologically active compounds have been prepared through dynamic kinetic
      resolution. This work gives access to a number of highly active catalysts of the
      type [Ru(biphosphane)(H)(eta(6)-cot)]BF(4). These catalysts have demonstrated
      their utility in the enantioselective hydrogenation of the tetrasubstituted
      cyclopentenone "dehydrodione", which leads to the commercially important perfume
      component Paradisone (Firmenich).

PMID- 14674783
TI  - Molecular tweezers and clips as synthetic receptors. Molecular recognition and
      dynamics in receptor-substrate complexes.
AB  - The molecular tweezers (1, 2) and clips (3-7) containing naphthalene and benzene
      spacer units can be synthesized via repetitive Diels-Alder reactions by the use
      of a molecular "Lego" set consisting of bisdienophiles (8, 9, 14) and dienes (10,
      13). The new receptors selectively bind electron-deficient neutral and cationic
      substrates in solution. Only the benzene-spaced tweezers form complexes with
      aliphatic substrates, whereas the other receptors bind aromatic substrates
      preferentially. HPLC studies with 1 and 2 chemically bonded to stationary phases
      give similar results for the heterogeneous systems. The formation of stable
      complexes between the water-soluble clip 5g and N-alkylpyridinium cations, such
      as N-methylnicotinamide and NAD(+), in aqueous solution illustrates the
      importance of the hydrophobic effect for arene-arene interactions. The dynamics
      of the complex formation and substrate mobility were investigated by the use of
      temperature-dependent liquid- and solid-state NMR spectroscopy. The electrostatic
      potential surface (EPS) of 1-7 is calculated to be surprisingly negative on the
      concave side of each molecule and, hence, complementary to the EPS of the
      electron-deficient substrates, suggesting that the attractive receptor-substrate
      interaction is here of predominantly electrostatic nature.

PMID- 14674784
TI  - Ligand-bridged oligomeric and supramolecular arrays of the hexanuclear rhenium
      selenide clusters--exploratory synthesis, structural characterization, and
      property investigation.
AB  - Transition metal clusters, by virtue of their well-defined structures and unique
      properties, present themselves as an attractive class of structural and
      functional building blocks for molecular and supramolecular construction.
      Summarized in this Account are highlights of our efforts utilizing face-capped
      octahedral [Re(6)(mu(3)-Se)(8)](2+) clusters as the fundamental building units to
      create a wide variety of preprogrammed architectures. These include molecular
      "Tinkertoys", featuring stereospecific cluster units bridged by multitopic
      ligands and extended arrays of clusters engineered via hydrogen bonding and
      secondary metal-ligand coordination.

PMID- 14674785
TI  - Substrate-mediated interactions and intermolecular forces between molecules
      adsorbed on surfaces.
AB  - Adsorbate interactions and reactions on metal surfaces have been investigated
      using scanning tunneling microscopy. The manners in which adsorbates perturb the
      surface electronic structure in their vicinity are discussed. The effects these
      perturbations have on other molecules are shown to be important in overlayer
      growth. Interactions of molecules with surface steps are addressed, and each
      molecule's electron affinity is shown to dictate its adsorption sites at step
      edges. Standing waves emanating from steps are demonstrated to effect transient
      molecular adsorption up to 40 A away from the step edge. Halobenzene derivatives
      are used to demonstrate how the surface is important in aligning reactive
      intermediates.

PMID- 14674786
TI  - Bone-specific drug delivery systems: approaches via chemical modification of bone
      seeking agents.
AB  - Despite several decades of progress, bone-specific delivery is still limited by
      the unique anatomical features of bone, which mainly consists of inorganic
      hydroxyapatite. A practical approach to this problem is to produce targeted drugs
      that have a high affinity for hydroxyapatite. Bisphosphonates are a class of
      synthetic compounds structurally related to pyrophosphate. Bisphosphonates
      rapidly localise on the bone surface after being administered either
      intravenously or orally, since the P-C-P portion of the bisphosphonate structure
      has high affinity for hydroxyapatite. Therefore, bisphosphonate modification
      might be a promising method for targeting drugs selectively to the bone.
      Bisphosphonate-conjugated drugs are hydrophilic and highly water-soluble due to
      the acidic nature of the bisphosphonate moiety at physiological pH, and therefore
      they hardly permeate through the biological membrane of soft tissues. These
      physicochemical changes also reduce the intrinsic susceptibility of the drug to
      metabolism, promoting urinary or biliary excretion as unchanged drug. All these
      physicochemical and pharmacokinetic alterations contribute to the exceptional
      skeletal disposition of bisphosphonate-conjugated drugs. Bisphosphonate
      conjugation is based on chemical modification of the targeting molecule, and
      therapeutically optimised bisphosphonate derivatives have to be custom-developed
      on a case-by-case basis. The bisphosphonate moiety is usually coupled with the
      targeting drug through a specific linkage. The high affinity of bisphosphonate
      conjugates for the bone is not simply dependent on the bisphosphonate moiety but
      on the resultant molecule as a whole, including the linker and the linked drug.
      Lipophilicity (represented as log P) appears to be an appropriate index for
      predicting the osteotropic properties of bisphosphonate derivatives. Several
      strategies using bisphosphonate-conjugated drugs have been investigated at a
      laboratory level with the aim of obtaining therapeutically optimised treatments
      for conditions such as osteoporosis, osteoarthritis and bone cancer. In each
      case, the intention is to achieve prolonged local exposure to high concentrations
      of the targeting drug, thereby improving therapeutic index by enhancing
      pharmacological efficacy and minimising systemic adverse effects. Although most
      examples of bone-specific drug delivery via bone-seeking agents still remain in
      preclinical studies, several phosphonate-coupled radiopharmaceuticals, such as
      samarium-153 complexed to tetraphosphonate, are expected to be an effective pain
      palliation therapies for metastatic bone cancer and are currently being developed
      in clinical trials. Furthermore, recent reports on bisphosphonate-modified
      proteins have illustrated the feasibility of bone-specific delivery of
      biologically active protein drugs, such as cytokines and growth factors.

PMID- 14674787
TI  - Role of orphan nuclear receptors in the regulation of drug-metabolising enzymes.
AB  - During the past several years, important advances have been made in our
      understanding of the mechanisms that regulate the expression of genes that
      determine drug clearance, including phase I and phase II drug-metabolising
      enzymes and drug transporters. Orphan nuclear receptors have been recognised as
      key mediators of drug-induced changes in both metabolism and efflux mechanisms.
      In this review, we summarise recent findings regarding the function of nuclear
      receptors in regulating drug-metabolising and transport systems, and the
      relevance of these receptors to clinical drug-drug interactions and the
      development of new drugs. Emphasis is given to two newly recognised 'orphan'
      receptors (the pregnane X receptor [PXR] and the constitutive androstane receptor
      [CAR]) and their regulation of cytochrome P450 enzymes, such as CYP3A4, CYP2Cs
      and CYP2B6; and transporters, such as P-glycoprotein (MDR1), multidrug resistance
      associated proteins (MRPs) and organic anion transporter peptide 2 (OATP2).
      Although 'cross-talk' occurs between these two receptors and their target
      sequences, significant species differences exist between ligand-binding and
      activation profiles for both receptors, and PXR appears to be the predominant or
      'master' regulator of hepatic drug disposition in humans. Several important
      physiological processes, such as cholesterol synthesis and bile acid metabolism,
      are also tightly controlled by certain ligand-activated orphan nuclear receptors
      (farnesoid X receptor [FXR] and liver X receptor [LXR]). In general, their
      ability to bind a broad range of ligands and regulate an extensive array of genes
      that are involved in drug clearance and disposition makes these orphan receptors
      attractive targets for drug development. Drugs have the capacity to alter nuclear
      receptor expression (modulators) and/or serve as ligands for the receptors
      (agonists or antagonists), and thus can have synergistic or antagonistic effects
      on the expression of drug-metabolising enzymes and transporters. Coadministration
      of drugs that are nuclear receptor agonists or antagonists can lead to severe
      toxicity, a loss of therapeutic efficacy or an imbalance in physiological
      substrates, providing a novel molecular mechanism for drug-drug interactions.

PMID- 14674789
TI  - Clinical pharmacokinetics of galantamine.
AB  - Galantamine is the most recently approved cholinergic drug for the treatment of
      Alzheimer's disease, the most common type of dementia. Vascular dementia and
      Alzheimer's disease with cerebrovascular disease are also common in older
      patients. Dementia affects cognition, causes losses in ability to perform
      activities of daily living and often results in the emergence of psychiatric and
      abnormal behavioural symptoms. Dementia also results in an ever-increasing burden
      and a decreased quality of life for caregivers. Treatments for dementia,
      particularly Alzheimer's disease, have focused on improving function in the
      cholinergic system. Vascular dementia and diffuse Lewy body dementia are also
      associated with significant defects in cholinergic function. Galantamine works by
      inhibiting acetylcholinesterase and by allosterically modulating nicotinic
      receptors. In clinical trials, galantamine has shown benefits in the domains of
      cognition, function in activities of daily living, and behaviour. Galantamine is
      about 90% bioavailable and displays linear pharmacokinetics. It has a relatively
      large volume of distribution and low protein binding. Metabolism is primarily
      through the cytochrome P450 system, specifically the CYP2D6 and CYP3A4
      isoenzymes. Population pharmacokinetic modelling with galantamine has shown that
      the variables affecting clearance are age, sex, and bodyweight. Model simulations
      demonstrate the importance of a slower dose-escalation schedule in patients with
      moderate hepatic impairment. In several large trials, galantamine has been shown
      to be well tolerated, with most adverse events being mild-to-moderate and
      gastrointestinal in nature. Based on the literature and clinical trial
      experience, galantamine appears to be an excellent treatment option for patients
      with Alzheimer's disease, vascular dementia or Alzheimer's disease with
      cerebrovascular disease.

PMID- 14674788
TI  - Stereoselectivity in the pharmacodynamics and pharmacokinetics of the chiral
      antimalarial drugs.
AB  - Several of the antimalarial drugs are chiral and administered as the racemate.
      These drugs include chloroquine, hydroxychloroquine, quinacrine, primaquine,
      mefloquine, halofantrine, lumefantrine and tafenoquine. Quinine and quinidine are
      also stereoisomers, although they are given separately rather than in
      combination. From the perspective of antimalarial activity, most of these agents
      demonstrate little stereoselectivity in their effects in vitro. Mefloquine, on
      the other hand, displays in vitro stereoselectivity against some strains of P.
      falciparum, with a eudismic ratio of almost 2 : 1 in favour of the (+)
      enantiomer. Additionally, for some of these agents (e.g. halofantrine,
      primaquine, chloroquine), stereoselectivity has been noted in the ability of the
      enantiomers to cause certain adverse effects. In recent years, stereospecific
      analytical methods capable of measuring the individual enantiomers after the
      administration of racemic drugs have been reported for a number of chiral
      antimalarial drugs. These assays have revealed that almost all the studied
      antimalarial drugs display stereoselectivity in their pharmacokinetics, leading
      to enantioselectivity in their plasma concentrations. Whereas the oral absorption
      of these agents appears to be non-stereoselective, stereoselectivity is often
      seen in their volume of distribution and/or clearance. With regard to
      distribution, plasma protein binding of some chiral antimalarial drugs exhibits a
      significant degree of stereoselectivity, leading to stereoselective distribution
      to blood cells and other tissues. Because of their low hepatic extraction ratios,
      stereoselective plasma protein binding also contributes to the stereoselectivity
      in the metabolism of these drugs. Chiral metabolites are formed from some parent
      antimalarial drugs, although stereoselective aspects of the pharmacokinetics of
      the metabolites are not well understood. It is concluded that knowledge of the
      stereoselective aspects of these agents may be helpful in better understanding
      their mechanisms of action and possibly optimising their clinical safety and/or
      effectiveness.

PMID- 14674790
TI  - Nonparametric expectation maximisation (NPEM) population pharmacokinetic analysis
      of caffeine disposition from sparse data in adult caucasians: systemic caffeine
      clearance as a biomarker for cytochrome P450 1A2 activity.
AB  - OBJECTIVE: To explore the ability of the nonparametric expectation maximisation
      (NPEM) method of population pharmacokinetic modelling to deal with sparse data in
      estimating systemic caffeine clearance for monitoring and evaluation of
      cytochrome P450 (CYP) 1A2 activity. DESIGN AND PARTICIPANTS: Nonblind, single
      dose clinical investigation in 34 non-related adult Bulgarian Caucasians (18
      women and 16 men, aged between 18 and 62 years) with normal and reduced renal
      function. METHODS: Each participant received oral caffeine 3 mg/kg. Two blood
      samples per individual were taken according to the protocol for measuring
      caffeine plasma concentrations. A total of 67 measured concentrations were used
      to obtain NPEM estimates of caffeine clearance. Paraxanthine/caffeine plasma
      ratios were calculated and correlated with clearance estimates. Graphical methods
      and tests for normality were applied and parametric and nonparametric statistical
      tests were used for comparison. RESULTS: NPEM median estimates of caffeine
      absorption and elimination rate constants, k(a) = 4.54 h(-1) and k(el) = 0.139 h(
      1), as well as of fractional volume of distribution and plasma clearance, V(S1) =
      0.58 L/kg and CL(S1) = 0.057 L/h/kg, agreed well with reported values from more
      'data rich' studies. Significant correlations were observed between
      paraxanthine/caffeine ratios at 3, 8 and 10 hours and clearance (Spearman rank
      correlation coefficients, r(s), >0.74, p </= 0.04). Sex or renal function caused
      no significant differences in clearance. Heavy smokers and drinkers showed 2-fold
      higher CYP1A2 activity. Normality tests and graphical methods of analysing
      caffeine clearance supported a non-Gaussian and multicomponent distribution of
      CYP1A2 activity. CONCLUSIONS: Collectively, the results show that the NPEM method
      is suitable and relevant for large-scale epidemiological studies of population
      phenotyping for cancer susceptibility and for abnormal liver function by
      monitoring CYP1A2 activity based on sparse caffeine data.

PMID- 14674791
TI  - Clinical pharmacodynamics of linezolid in seriously ill patients treated in a
      compassionate use programme.
AB  - OBJECTIVE: To characterise the pharmacokinetic-pharmacodynamic relationships for
      linezolid efficacy. DESIGN AND STUDY POPULATION: Retrospective nonblinded
      analysis of severely debilitated adult patients with numerous comorbid conditions
      and complicated infections enrolled under the manufacturer's compassionate use
      programme. METHODS: Patients received intravenous or oral linezolid 600 mg every
      12 hours. Plasma concentrations were obtained and a multicompartmental
      pharmacokinetic model was fitted. Numerical integration of the fitted functions
      provided the area under the concentration-time curve over 24 hours (AUC), the
      ratio of AUC to minimum inhibitory concentration (AUC/MIC) and the percentage of
      time that plasma concentrations exceeded the MIC (%T>MIC). MAIN OUTCOME MEASURES:
      Modelled pharmacodynamic outcomes of efficacy included probabilities of
      eradication and clinical cure (multifactorial logistic regression, nonparametric
      tree-based modelling, nonlinear regression) and time to bacterial eradication
      (Kaplan-Meier and Cox proportional hazards regression). Factors considered
      included AUC/MIC, %T>MIC, site of infection, bacterial species and MIC, and other
      medical conditions. RESULTS: There were 288 cases evaluable by at least one of
      the efficacy outcomes. Both %T>MIC and AUC/MIC were highly correlated (Spearman
      r2 = 0.868). In our analyses, within specific infection sites, the probability of
      eradication and clinical cure appeared to be related to AUC/MIC (eradication:
      bacteraemia, skin and skin structure infection [SSSI], lower respiratory tract
      infection [LRTI], bone infection; clinical cure: bacteraemia, LRTI) and %T>MIC
      (eradication: bacteraemia, SSSI, LRTI; clinical cure: bacteraemia, LRTI). Time to
      bacterial eradication for bacteraemias appeared to be related to the AUC, %T>MIC
      and AUC/MIC. For most sites, AUC/MIC and %T>MIC models performed similarly.
      CONCLUSIONS: Higher success rates for linezolid may occur at AUC/MIC values of 80
      120 for bacteraemia, LRTI and SSSI. Chance of success in bacteraemia, LRTI and
      SSSI also appear to be higher when concentrations remain above the MIC for the
      entire dosing interval.

PMID- 14674792
TI  - A sampling method for comparing fungal concentrations in carpets.
AB  - A microvacuum method is described for sampling fungal contaminants in carpet dust
      and reporting the results on an area basis. When sampling parameters such as
      suction force, contact time, and area sampled were held constant, and the results
      were reported on an area basis, fungal concentrations were associated with the
      potential for water intrusion, a determinant of exposure. Carpet dust samples
      were collected in open-face 25-mm cassettes containing 0.8 micro m mixed
      cellulose ester filters. The airflow rate was calibrated at 10 L/min, and the
      open-faced cassette was held firmly against the carpet at 20 separate spots for a
      period of 5 sec at each spot. An area of 98 cm(2) of carpet was sampled with each
      cassette. A total of 58 carpet dust samples were collected in 31 residential
      condominium units using the described methodology. The carpets were stratified
      into three groups: (1) controls and those at centers of rooms, (2) at sliding
      glass doors and under windows, and (3) in areas of water intrusion reported by
      the occupant. The geometric mean concentrations (GM) of total fungi increased in
      the listed order, as did the GM concentrations of Penicillium spp. and
      Aspergillus spp. detected in the samples. In addition, the 95% confidence
      intervals on the GM concentrations for total fungi could be used to classify the
      carpets into three groups: uncontaminated, potentially contaminated, and
      contaminated.

PMID- 14674793
TI  - Health care workers: risk factors for nonlatex and latex gloves during surgery.
AB  - This study examined glove failure and related factors in both nonlatex and latex
      surgical gloves after routine use. A federally funded research study was
      conducted to collect surgical gloves from those directly involved in surgical
      procedures. All gloves were examined in the laboratory for both visual defects
      and barrier integrity. A total of 11,118 usable surgical gloves were examined.
      The overall defect rate was 7.8%; nonlatex gloves were significantly more likely
      to fail (8.4%) than latex gloves (6.9%). The majority of defects in the latex
      gloves (90%) and nonlatex gloves (70%) were not detected by visual examination.
      Separate logistic regression models examined predictors of defects for the
      gloves. The only factor that increased the odds of a defect for a latex glove was
      duration of use over 6 hours. Factors increasing the odds of a defect in nonlatex
      gloves included gloves worn by a scrub person and gloves used in certain surgical
      services. Scrub persons had a higher defect rate despite wearing their gloves for
      a significantly shorter time than other health care workers. Latex and nonlatex
      gloves fail under different conditions. Latex gloves fail primarily due to length
      of use, whereas nonlatex gloves are more sensitive to conditions of us (e.g.,
      type of health care worker and type of surgery). Providers can help guard against
      glove defects by double gloving and by changing gloves often, especially when
      using nonlatex gloves in higher-risk surgeries.

PMID- 14674794
TI  - Speech intelligibility during respirator wear: influences of respirator speech
      diaphragm size and background noise.
AB  - This study assessed the effect of respirator speech device size on speech
      intelligibility and the impact of background noise on respirator communications
      effectiveness. Thirty-five subjects completed modified rhyme test (MRT) speech
      intelligibility testing procedures with and without a respirator under background
      noises of 40, 60, and 80 dBA. Respirator wear conditions included the use of one
      unmodified and three mechanical speech diaphragms modified to reduce the surface
      area of the vibrating inner membrane available for sound transmission. Average
      MRT scores decreased linearly as background noise levels increased for all
      conditions. Lower MRT scores were observed for all respirator speech diaphragm
      conditions compared to the nonrespirator condition within each noise category.
      Average MRT scores differed significantly between the unmodified speech diaphragm
      and one with a 70% reduced surface area with a 40-dBA background noise. However,
      MRT scores were similar between the modified and unmodified diaphragms at both
      the 60- and 80-dBA noise levels. These findings provide evidence that alternate
      designs of mechanical-type respirator speech devices can be achieved without
      further degradation of speech sound transmission.

PMID- 14674795
TI  - Comparison of task-based estimates with full-shift measurements of noise
      exposure.
AB  - Using a large data set of noise exposure measurements on construction workers,
      task-based (TB) and full-shift (FS) exposure levels were compared and analyzed
      for the sources and magnitudes of the error associated with this methodology.
      Data-logging dosimeters recorded A-weighted sound pressure levels in decibels
      using Occupational Safety and Health Administration criteria for every minute of
      monitoring and were combined with information from task cards completed by
      subjects. Task-related information included trade, construction site type,
      location, activity, and tool. A total of 502 FS measurements were made, including
      248,677 min of exposure on five construction trades. Six TB models of varying
      degrees of specificity were fit to the minute-level data and the results used to
      obtain TB estimates of the daily FS exposure levels. The TB estimates were
      derived using the predictions alone and also including subject and shift-specific
      residual means and variances. The predictions alone, which ignore within-task
      variability, produced a significant negative bias that was corrected by
      incorporation of the residual variance. This bias is only an issue in this
      setting in which the exposure of interest is noise, which follows a nonlinear
      averaging relationship. These estimates explained 10 to 60% of the variability in
      FS measures; adding the residual mean produced estimates that explained about 90%
      of the variability. In summary, TB estimates are important for exposure
      estimation when task time varies substantially. However, TB estimates include a
      substantial degree of error when there is large interindividual or intershift
      variability in exposure levels for a given task. Methods to improve the
      prediction of task-associated exposure, or adjusting for individual and shift
      differences, are needed.

PMID- 14674796
TI  - Fatigue in the forearm resulting from low-level repetitive ulnar deviation.
AB  - This study measured low-frequency fatigue (LFF) in the extensor carpi ulnaris
      (ECU) muscle while workers completed a repetitive ulnar deviation task. Using a
      repeated measures design, 10 healthy women participated in three conditions, each
      lasting 2 consecutive days: a control condition in which subjects remained
      inactive, and two repetitive work conditions involving repeated ulnar deviation
      of the wrist at 20 and 25 repetitions per minute at individual workloads deemed
      acceptable for 8 hours through a psychophysical protocol. LFF of the ECU muscle
      and self-reported levels of fatigue were recorded eight times throughout the
      control and workdays before (time 0), during (2, 4.25, 6.75, 8 hours), and after
      (9, 10, and 11 hours) exposure. The ratio of the isometric force produced by
      electrical stimulus at 20 pulses per second (pps) to the isometric force produced
      by 50 pps provided the measure of LFF. The ratios were lower on workdays compared
      with the control days, indicating the presence of LFF during repetitive work.
      During repetitive work the ratios decreased during the day, indicating the
      muscles fatigued as the day progressed. The psychophysically determined
      workloads, although not creating noticeable discomfort to the subjects, were high
      enough to create low levels of muscle fatigue.

PMID- 14674797
TI  - Sampling and analysis of aircraft engine cold start particles and demonstration
      of an electrostatic personal particle sampler.
AB  - Aircraft engines emit an aerosol plume during startup in extremely cold weather
      that can drift into areas occupied by flightline ground crews. This study tested
      a personal sampler used to assess exposure to particles in the plume under
      challenging field conditions. Area and personal samples were taken at two U.S.
      Air Force (USAF) flightlines during the winter months. Small tube-and-wire
      electrostatic precipitators (ESPs) were mounted on a stationary stand positioned
      behind the engines to sample the exhaust. Other ESPs were worn by ground crews to
      sample breathing zone concentrations. In addition, an aerodynamic particle sizer
      3320 (APS) was used to determine the size distribution of the particles. Samples
      collected with the ESP were solvent extracted and analyzed with gas
      chromatography-mass spectrometry. Results indicated that the plume consisted of
      up to 75 mg/m(3) of unburned jet fuel particles. The APS showed that nearly the
      entire particle mass was respirable, because the plumes had mass median diameters
      less than 2 micro m. These tests demonstrated that the ESP could be used at cold
      USAF flightlines to perform exposure assessments to the cold start particles.

PMID- 14674799
TI  - Strength capabilities and subjective limits in repetitive manual exertions: task
      and hand dominance effects.
AB  - Strength and subjectively determined exertion limits are used widely for
      ergonomic evaluation. Although compilations of such data for the hand and finger
      exist, several important limitations include the use of inexperienced
      participants and constrained postures. In this study both strength and maximum
      acceptable limits (MAL, 2-hour duration) were obtained from both industrial
      workers and inexperienced volunteers in 10 simulated hand-intensive automotive
      assembly tasks. To expand the applicability of the results, the effects of hand
      dominance were also determined. Results were compared with existing
      recommendations (by Kodak and the American Conference of Governmental Industrial
      Hygienists threshold limit value for hand-intensive activities), and showed that
      across the diverse tasks the former yields values slightly below the 1st
      percentile of MAL, whereas the latter values are slightly higher than the 25th
      percentile. MALs were found to be approximately 50% of strength, consistent with
      earlier reports, and suggesting that acceptable limits are strongly influenced by
      physical capacity. Substantial differences ( approximately 30%) in strength and
      MALs were found between the two participant groups, emphasizing that participants
      should resemble the target population. Hand-dominance effects were statistically
      significant though of moderate size ( approximately 5%). Strength and MAL
      distributions are provided that can be used for evaluation and design of a
      variety of hand-intensive occupational tasks.

PMID- 14674798
TI  - A personal sampler for aircraft engine cold start particles: laboratory
      development and testing.
AB  - Industrial hygienists in the U.S. Air Force are concerned about exposure of their
      personnel to jet fuel. One potential source of exposure for flightline ground
      crews is the plume emitted during the start of aircraft engines in extremely cold
      weather. The purpose of this study was to investigate a personal sampler, a small
      tube-and-wire electrostatic precipitator (ESP), for assessing exposure to
      aircraft engine cold start particles. Tests were performed in the laboratory to
      characterize the sampler's collection efficiency and to determine the magnitude
      of adsorption and evaporation artifacts. A low-temperature chamber was developed
      for the artifact experiments so tests could be performed at temperatures similar
      to actual field conditions. The ESP collected particles from 0.5 to 20 micro m
      diameter with greater than 98% efficiency at particle concentrations up to 100
      mg/m(3). Adsorption artifacts were less than 5 micro g/m(3) when sampling a high
      concentration vapor stream. Evaporation artifacts were significantly lower for
      the ESP than for PVC membrane filters across a range of sampling times and
      incoming vapor concentrations. These tests indicate that the ESP provides more
      accurate exposure assessment results than traditional filter-based particle
      samplers when sampling cold start particles produced by an aircraft engine.

PMID- 14674800
TI  - The application of a job exposure matrix in the natural gas industry.
AB  - A questionnaire was designed, implemented, and analyzed, using a job exposure
      matrix format, to profile jobs in the Pipeline Division of a natural gas company
      with respect to possible hazardous exposures. The categories of chemical,
      physical, ergonomic, biological, and psychological hazards were surveyed. The
      first stage was to formulate and confirm a list of hazardous agents extant within
      the Pipeline Operations. This was done by making on-site observations and
      interviewing safety supervisors and workers, as well as by exploring the
      literature on the natural gas industry. The second stage of the project entailed
      the collection of data about whether a particular hazardous agent was present at
      a location, and if so, which workers were exposure to it, and at what intensity
      and frequency they were exposed. This assessment was made by groups identified as
      expert assessors, senior workers who were familiar with the processes and range
      of job titles at their locations. These experienced workers rated all job titles
      for workers at that site. The final stage of the project was to critically
      examine and validate the data collected. Three analyses were performed. The first
      was a comparison of the assessments with known outcomes of the medical
      surveillance testing that was completed in 1995. Secondly, the agreement between
      the assessments done by the expert assessor group, and a rating done by the
      jobholder, was examined. Finally, consideration was given to the sureness
      expressed by each of the rating groups about the analysis they had provided.

PMID- 14674801
TI  - Facial dimensions and predictors of fit for half-mask respirators in Koreans.
AB  - This study investigated the relationship between facial dimensions and the fit of
      half-mask respirators using fit factors and selected good facial dimension
      predictor(s) of fit for designing respirators for Korean workers. Three different
      brands of half-mask respirators-YS, SG, and 3M-were fit-tested on 112 men and 38
      women using TSI Portacount 8020, and fit factors were determined. Before fit
      testing, 10 facial dimensions were measured. Data were analyzed by descriptive
      statistics, Pearson's correlation analysis, and quadratic polynomial regression
      analysis with log-transformed fit factors (LNFF). However, some of the
      relationships between LNFF and facial dimensions in brand/gender subgroups were
      found to be curvilinear rather than linear. Because this result indicated that a
      multiple polynomial regression model including quadratic terms might be more
      appropriate than a multiple linear regression, data were also analyzed with a
      quadratic term by examination of the coefficient of partial correlation. No
      common facial dimension variables were found to be significant for all nine
      brand/gender subgroups, but the coefficient of regression for the linear term of
      the bitragion-menton arc was significant in five of nine brand/gender subgroups
      including male subjects of all three respirator brands. The 3M mask had the
      highest coefficient of determination values compared with other brands. Using the
      quadratic term for the 3M mask, face width (bizygomatic breadth) and nose
      protrusion were good predictors of half-mask fit. In four of nine brand/gender
      subgroups, nose protrusion was a good predictor of fit through analysis using a
      quadratic term. Results indicate that face width, bitragion-menton arc, and nose
      protrusion should be preferentially considered when designing a half-mask
      respirator for Korean workers.

PMID- 14674802
TI  - Loss of straight metalworking fluid samples from evaporation during sampling and
      desiccation.
AB  - Straight metalworking fluids (MWFs) were used to evaluate the potential for the
      loss of MWF mass from filters. Two methods were used to study the stability of
      MWF mass on filter media. The first was to spike known amounts of MWF onto
      polyvinyl chloride (PVC) filters, store the filters over silica gel desiccant,
      and take repeated gravimetric measurements of the filters at intervals of 1, 2,
      and 3 days. An MWF aerosol mist was generated in a test chamber and collected on
      PVC filters for the second experimental method. Additional clean air was drawn
      through a subset of filters (range 0.02-0.48 m(3)), which were then stored over
      silica gel prior to weighing. Losses due to desiccation were found in filters
      that had not been exposed to airflow, as well as for filters after aspiration.
      The losses occurring in spiked filters (range of mean 2.6-15.2%) were higher than
      those in collected filters (range 0.7-8.1%). The MWF aerosol mass collected on
      PVC filters decreased with the increasing volume of clean air passing through the
      filter. In a multiple regression model, to predict the loss of collected MWF due
      to desiccation, loading mass, fresh MWF, and air passing time of 10 min were
      significant predictors (p=.0001, R(2)=.374). In particular, only air passage of
      10 min was significantly higher (2.13%) than the reference air passage (p=.0054).
      The investigators concluded that MWF aerosol collected on PVC filters may be lost
      to evaporation under conditions typical of shipment, storage, and desiccation of
      sample filters, and with airflow through the filter.

PMID- 14674803
TI  - The thermo-hand method: evaluation of a new indicator pad for acid permeation of
      chemical protective gloves.
AB  - The thermo-hand method was developed to evaluate a new indicator pad for acid
      permeation through chemical protective gloves under in-use conditions (controlled
      conditions for the hand's skin temperature, hand movements, and relative humidity
      inside gloves). An indicator pad was used to detect both organic and inorganic
      acid permeation through glove materials. Breakthrough times for five types of
      gloves were determined and found to range from 5 to 308 min for propionic acid,
      from 4 to 293 min for acrylic acid, and from 15 min to >6 hours for HCl.
      Quantification was performed for propionic and acrylic acids following solvent
      desorption and gas chromatography. Both acids exhibited >99% adsorption
      (including the volume of acid, which reacted with an indicator to contribute the
      color change) on the pads at a spiking level of 1.8 micro L for each acid. Acid
      recovery for the system was calculated for each acid, with results ranging from
      52-72% (RSD < or =4.0%) for both acids over the spiking range 0.2-1.8 micro L.
      The quantitative mass of the acids on the pads at the time of breakthrough
      detection ranged from 253-276 and 270-296 micro g/cm(2) for propionic acid and
      acrylic acid, respectively. The thermo-hand method and a new acid indicator pad
      together should be useful in detecting, collecting, and quantitatively analyzing
      acid permeation samples in the workplace.

PMID- 14674804
TI  - Identification of agricultural tasks important to cumulative exposures to
      inhalable and respirable dust in California.
AB  - Little data exists on the determinants of agricultural dust exposure,
      particularly in dry climates. Annual exposure indices to inhalable and respirable
      dust were constructed by exposure estimates for specific tasks, task duration,
      and task frequency. The estimates of exposure levels were based on actual field
      measurements and subjective dust exposure ranking. The task duration and
      frequency data were obtained by questionnaire from 546 farm operators in
      California. Annual exposure indices were analyzed to determine which tasks were
      major contributors to chronic dust exposure. The important tasks were identified
      by comparisons of the cumulative distribution of exposures for all tasks and the
      cumulative distribution of exposures with one task deleted. Thirteen and 11 tasks
      were identified to be important to both inhalable and respirable dust exposures,
      respectively. Tasks identified to be important to agricultural exposure may be
      ascribed to exposure duration more than to exposure intensity. Information on
      task-specific exposure is important for developing control strategies in the
      agricultural workplace.

PMID- 14674805
TI  - The effect of the size of openings on contaminant control between two adjacent
      spaces with differing air pressures.
AB  - Maintaining a pressure difference between zones or rooms is an important method
      of controlling the spread of air contaminants. Where it is well managed, this
      method will provide better control with less energy consumption, particularly in
      health care or electronic component manufacturing facilities. However, it is
      difficult to control a multizone system to maintain a pressure difference when
      there is an opening between two adjacent zones. To prevent the spread of
      contaminants into the "clean" zone, it is necessary to maintain some level of
      pressure difference. This study investigates the effect of changing the opening
      size between two small rooms and evaluates the contaminant dispersion at varying
      pressure difference values by using a tracer gas technique. The influence of
      several parameters, such as air pressure difference, surface area of opening, and
      supply air volume between two interior zones on contaminant transportation
      through an opening was investigated. The control pressure differences between two
      adjacent spaces were arranged from 2.49 to 14.69 Pa. Pressure difference was
      found to be an effective predictor of contaminant diffusion. An empirical
      relationship between pressure and opening size is presented between two rooms
      that will predict contaminant control required levels. The coefficient of
      determination (R(2)) of this correlation is 0.9226.

PMID- 14674806
TI  - Correlation between quantitative fit factors and workplace protection factors
      measured in actual workplace environments at a steel foundry.
AB  - Past studies have found little or no correlation between workplace protection
      factors (WPFs) and quantitative fit factors (FFs). This study investigated the
      effect of good- and poor-fitting half-facepiece, air-purifying respirators on
      protection in actual workplace environments at a steel foundry and the
      correlation between WPFs and FFs. Fifteen burners and welders, who wore
      respirators voluntarily, and chippers participated in this study. Each subject
      was fit-tested with two respirator models each with three sizes, for a total of
      six fit-tests. Models and sizes were assigned this way to provide a wide range of
      FFs among study participants. Each worker donned the respirator twice per day (at
      the beginning of the shift and following the lunch break) for 2 days.
      Quantitative FFs were first obtained for each donning using the PortaCount Plus
      trade mark in a separate room. Without redonning the respirators, workers
      performed normal work for 1 to 2 hours, and WPFs were measured by collecting
      ambient and in-facepiece samples simultaneously. A second fit-test was conducted
      without disturbing the respirator. FFs were obtained by averaging the results
      from the first and second fit-tests. The resulting FFs had a geometric mean (GM)
      of 400 (range=10-6010) and a geometric standard deviation (GSD) of 6.1. Of the 55
      valid donnings, 43 were good fitting (FFs> or =100) and 12 were poor fitting
      (FFs<100). The WPFs had a GM of 920 (range=13-230,000) and a GSD of 17.8. The
      WPFs were found to be significantly correlated with the FFs (R(2)=.55 and p
      value=.0001). Therefore, FF was shown to be a meaningful indicator of respirator
      performance in actual workplace environments.

PMID- 14674808
TI  - Comparison of emission models with computational fluid dynamic simulation and a
      proposed improved model.
AB  - Understanding source behavior is important in controlling exposure to airborne
      contaminants. Industrial hygienists are often asked to infer emission information
      from room concentration data. This is not easily done, but models that make
      simplifying assumptions regarding contaminant transport are frequently used. The
      errors resulting from these assumptions are not yet well understood. This study
      compares emission estimates from the single-zone completely mixed (CM-1), two
      zone completely mixed (CM-2), and uniform diffusivity (UD) models with the
      emissions set as boundary conditions in computational fluid dynamic (CFD)
      simulations of a workplace. The room airflow and concentration fields were
      computed using Fluent 4. These numerical experiments were factorial combinations
      of three source locations, five receptor locations, three dilution airflow rates,
      and two generation rate profiles, constant and time-varying. The aim was to
      compute plausible concentration fields, not to simulate exactly the processes in
      a real workroom. Thus, error is defined here as the difference between model and
      CFD predictions. For the steady-state case the UD model had the lowest error.
      When the source near-field contained the breathing zone receptor, the CM-2 model
      was applied. Then, in decreasing agreement with CFD were UD, CM-2, and CM-1.
      Averaging over all source and receptor locations (CM-2 applied for only one), in
      decreasing order of agreement with CFD were UD, CM-1, and CM-2. Source and
      receptor location had large effects on emission estimates using the CM-1 model
      and some effect using the UD model. A location-specific mixing factor (location
      factor) derived from steady-state concentration gradients was used to build a
      more accurate time-dependent emission model, CM-L. Total mass emitted from a time
      varying source was modeled most accurately by CM-L, followed by CM-1 and CM-2.

PMID- 14674809
TI  - How are stereotypes maintained through communication? The influence of stereotype
      sharedness.
AB  - Recent research has suggested that interpersonal communication may be an
      important source of stereotype maintenance. When communicated through a chain of
      people, stereotype-relevant information tends to become more stereotypical, thus
      confirming the stereotypes held by recipients of communication. However, the
      underlying mechanisms of this phenomenon have yet to be fully determined. This
      article examines how the socially shared nature of stereotypes interacts with
      communication processes to maintain stereotypes in communication chains. In 3
      experiments, participants communicated a stereotype-relevant story through 4
      person chains using the method of serial reproduction. Manipulations included the
      extent to which communicators believed their audience and other community members
      shared and endorsed their stereotypes, and also the extent to which they actually
      shared the stereotypes. The shared nature of stereotypes was found to be a strong
      contributor to rendering the story more stereotypical in communication. This is
      discussed in relation to the maintenance of stereotypes through communication.

PMID- 14674807
TI  - Health and safety management system audit reliability pilot project.
AB  - This pilot study assessed occupational health and safety (OHS) management system
      audit finding reliability using a modified test-retest method. Two industrial
      hygienists with similar training and education conducted four, 1-day management
      system audits in four dissimilar organizational environments. The researchers
      examined four auditable sections (employee participation, training, controls, and
      communications) contained in a publicly available OHS management system
      assessment instrument. At each site, 102 auditable clauses were evaluated using a
      progressive 6-point scale. The team examined both the consistency of and
      agreement between the scores of the two auditors. Consistency was evaluated by
      calculating the Pearson r correlations for the two auditors' scores at each site
      and for each section within each site. Pearson correlations comparing overall
      scores for each site were all very low, ranging from 0.206 to 0.543. Training and
      communication system assessments correlated the highest, whereas employee
      participation and control system scores correlated the least. To measure
      agreement, t-tests were first calculated to determine whether the differences
      were statistically significant. Aggregate mean scores for two of the four sites
      were significantly different. Of the 16 total sections evaluated (i.e., 4
      sections per site), seven scores were significantly different. Finally, the
      agreement of the scores between the two auditors for the four sites was evaluated
      by calculating two types of intraclass correlation coefficients, all of which
      failed to meet the minimum requirement for agreement. These findings suggest that
      opportunities for improving the reliability of the instrument and the audit
      process exist. Future research should include governmental and commercial OHS
      program assessments and related environmental management systems and their
      attendant audit protocols.

PMID- 14674810
TI  - Task interest and actual performance: the moderating effects of assigned and
      adopted purpose goals.
AB  - This research examined whether and which purpose goals moderate the relationship
      between task interest and actual performance and whether assigned goals have
      different effects (Study 1) than adopted goals (Study 2). Two studies were
      conducted using a full 2 X 2 design of the performance-mastery and approach
      avoidance distinctions, plus control conditions. In the control conditions, that
      is, in a neutral purpose goal context, the expected positive relationship between
      initial task interest and actual performance was found. In a purpose goal
      context, this link held only for a congruent mastery-approach goal (either
      assigned or adopted). The gain in task interest found in a neutral purpose
      context was observed in the purpose goal conditions only when participants
      attained their purpose goals. It was concluded that having an incongruent purpose
      goal may undermine the positive effect of prior task interest on actual
      performance as well as on subsequent task interest.

PMID- 14674811
TI  - On the behavioral consequences of infrahumanization: the implicit role of
      uniquely human emotions in intergroup relations.
AB  - Four experiments confirmed the hypothesis that people discriminate the out-group
      on the basis of the expression of uniquely human emotions. In Study 1, using a
      lost e-mail paradigm, the expression of a uniquely human emotion resulted in
      "nicer" replies when the sender was an in-group compared with an out-group
      member. The same pattern of results was obtained in Studies 2 and 3 using a
      conformity paradigm. In addition, perceived similarity was measured and proposed
      as a potential underlying mechanism (Study 3). Finally, using an approach
      avoidance procedure, Study 4 showed that people not only deprive the out-group of
      positive consequences as in the former studies but that people also act against
      the out-group. The role of infrahumanization underlying prejudice and
      discrimination is discussed.

PMID- 14674812
TI  - The warm glow heuristic: when liking leads to familiarity.
AB  - Five studies demonstrate that the positive valence of a stimulus increases its
      perceived familiarity, even in the absence of prior exposure. For example,
      beautiful faces feel familiar. Two explanations for this effect stand out: (a).
      Stimulus prototypicality leads both to positivity and familiarity, and (b).
      positive affect is used to infer familiarity in a heuristic fashion. Studies 1
      and 2 show that attractive faces feel more familiar than average ones and that
      prototypicality accounts for only part of this effect. In Study 3, the rated
      attractiveness of average faces was manipulated by contrast, and their perceived
      familiarity changed accordingly, although their inherent prototypicaliry remained
      the same. In Study 4, positive words felt more familiar to participants than
      neutral and negative words. Study 5 shows that the effect is strongest when
      recognition is difficult. The author concludes that both prototypicality and a
      warm glow heuristic are responsible for the "good-is-familiar" phenomenon.

PMID- 14674813
TI  - Assimilation for affiliation and contrast for control: complementary self
      construals.
AB  - People have knowledge about relationships (i.e., relational schemas) that is
      based on their experiences. Because most people have experience with
      complementary behavior (interaction partners behaving similarly in terms of
      affiliation but oppositely in terms of control), they expect complementary
      behavior in their relationships. Like other beliefs about relationships,
      expectations of complementarity affect self-construal. The authors provide
      evidence for complementary self-construal; people assimilate to relevant
      relationship partners on the affiliation dimension and contrast on the control
      dimension. Consistent with the proposed role of relationship knowledge in these
      effects, complementary self-construal was moderated by the familiarity of the
      target, whether people focused on their relationship with or the appearance of
      the target, and whether the context was relevant for the interpersonal dimension.

PMID- 14674814
TI  - Power in stereotypically masculine domains: a Social Influence Strategy X
      Stereotype Match model.
AB  - This work examines the hypothesis that stereotypes of groups to which low-power
      people belong should influence the perceptions and behavior of powerful people
      only when those stereotypes are both contextually relevant (e.g., women in
      masculine domains) and provide information of relevance given powerful people's
      beliefs about the relation between subordinates and goal attainment. Findings
      across two studies supported predictions. In a masculine domain, when high-power
      men were attentive to subordinate weaknesses that may produce thwarts to goal
      attainment, stereotypes of women defined the contextually relevant shortcomings
      of women, and stereotype-consistent high-power behaviors ensued. In contrast,
      when powerful men were attentive to subordinate strengths that may enhance goal
      strivings, stereotypes of women were uninformative (i.e., did not contain
      information about relevant strengths); female and male employees were responded
      to and, in turn, performed and reacted similarly. The implications of these
      findings for theorizing on the relation between power and stereotyping are
      discussed.

PMID- 14674815
TI  - Mind-reading accuracy in intimate relationships: assessing the roles of the
      relationship, the target, and the judge.
AB  - Using a video-review procedure, multiple perceivers carried out mind-reading
      tasks of multiple targets at different levels of acquaintanceship (50 dating
      couples, friends of the dating partners, and strangers). As predicted, the
      authors found that mind-reading accuracy was (a). higher as a function of
      increased acquaintanceship, (b). relatively unaffected by target effects, (c).
      influenced by individual differences in perceivers' ability, and (d). higher for
      female than male perceivers. In addition, superior mind-reading accuracy (for
      dating couples and friends) was related to higher relationship satisfaction,
      closeness, and more prior disclosure about the problems discussed, but only under
      moderating conditions related to sex and relationship length. The authors
      conclude that the nature of the relationship between the perceiver and the target
      occupies a pivotal role in determining mind-reading accuracy.

PMID- 14674816
TI  - The precarious couple effect: verbally inhibited men + critical, disinhibited
      women = bad chemistry.
AB  - When critical, verbally disinhibited women are paired with verbally inhibited
      men, relationship quality suffers, rendering the relationship precarious. This
      effect theoretically emerges when (a). verbally disinhibited women pair with
      relatively inhibited men (man-more-inhibited couples) and (b). the disinhibition
      of women in man-more-inhibited couples amplifies women's criticalness and
      alienates men. Three studies (Ns=437, 300, and 564) provided evidence that
      relationship quality suffered in man-more-inhibited couples; a 4th study (N=168)
      showed that the criticalness of women in man-more-inhibited couples did indeed
      undermine relationship quality. Implications for understanding the impact of
      gender expectations on relationships and for integrating behavioral and
      personological approaches to close relationships are discussed.

PMID- 14674817
TI  - Sexually selective cognition: beauty captures the mind of the beholder.
AB  - Across 5 experimental studies, the authors explore selective processing biases
      for physically attractive others. The findings suggest that (a). both male and
      female observers selectively attend to physically attractive female targets, (b).
      limiting the attentional capacity of either gender results in biased frequency
      estimates of attractive females, (c). although females selectively attend to
      attractive males, limiting females' attentional capacity does not lead to biased
      estimates of attractive males, (d). observers of both genders exhibit enhanced
      recognition memory for attractive females but attenuated recognition for
      attractive males. Results suggest that different mating-related motives may guide
      the selective processing of attractive men and women.

PMID- 14674818
TI  - Myopic social prediction and the solo comparison effect.
AB  - Four experiments explored the psychological processes by which people make
      comparative social judgments. Each participant chose how much money to wager on
      beating an opponent on either a difficult or a simple trivia quiz. Quiz
      difficulty did not influence the average person's probability of winning, yet
      participants bet more on a simple quiz than on a difficult quiz in the first 3
      experiments. The results suggest that this effect results from a tendency to
      attend more closely to a focal actor than to others. Experiment 4 directly
      manipulated focusing; when participants were led to focus on the opponent instead
      of themselves, the effect was reversed. The discussion relates the results to
      other literatures including overly optimistic self-evaluation, false consensus,
      overconfidence, and social comparison.

PMID- 14674819
TI  - Happiness and health: environmental and genetic contributions to the relationship
      between subjective well-being, perceived health, and somatic illness.
AB  - The aim was to identify genetic and environmental influences on the covariances
      between subjective well-being (SWB), perceived health, and somatic illness.
      Analyses were based on 6576 Norwegian twins aged 18-31. Heritabilities ranged
      from .24 to.66. SWB correlated .50 with perceived health, -.25 with
      musculoskeletal pain, and -.07 with allergy. Common genetic factors accounted for
      45%-60% of associations. SWB and perceived health was to a high extent influenced
      by the same genes (r(g)=.72 and.82 for males and females, respectively). For SWB
      and musculoskeletal pain, r-sub(g) =-.29 and -.42 for males and females,
      respectively. Effects were partly sex specific. Environmental factors shared by
      twins did not affect the covariances. Results support a differentiated view of
      SWB-health relations, and imply that both genes and environment play important
      roles in the associations between well-being and health.

PMID- 14674820
TI  - How are social identities linked to self-conception and intergroup orientation?
      The moderating effect of implicit theories.
AB  - Social identity approaches assume that social identification affects both self
      conception and intergroup orientation. The authors contend that such social
      identification effects are accentuated when people hold a fixed view of human
      character and attribute immutable dispositions to social groups. To these
      individuals, social identities are immutable, concrete entities capable of
      guiding self-conception and intergroup orientation. Social identification effects
      are attenuated when people hold a malleable view of human character and thus do
      not view social identities as fixed, concrete entities. The authors tested and
      found support for this contention in three studies that were conducted in the
      context of the Hong Kong 1997 political transition, and discussed the findings in
      terms of their implications for self-conceptions and the meaning of social
      identification.

PMID- 14674821
TI  - A dog's got personality: a cross-species comparative approach to personality
      judgments in dogs and humans.
AB  - This research offers a blueprint for how a cross-species comparative approach can
      be realized empirically. In a single design, parallel procedures and instruments
      were used in 2 species, dogs (Canis familiaris) and humans (Homo sapiens), to
      test whether personality differences exist and can be judged in dogs as
      accurately as in humans. Personality judgments of humans and dogs were compared
      on 3 accuracy criteria: internal consistency, consensus, and correspondence.
      Results showed that, on all 3 criteria, judgments of dogs were as accurate as
      judgments of humans. These findings are consistent with the evolutionary
      continuity hypothesis and suggest an important conclusion not widely considered
      by either personality or animal researchers: Personality differences do exist and
      can be measured in animals other than humans.

PMID- 14674822
TI  - Self-monitoring without awareness: using mimicry as a nonconscious affiliation
      strategy.
AB  - This research sought to extend the current conceptualization of self-monitoring
      by examining whether self-monitoring motives and behaviors can operate outside of
      conscious awareness. Two studies examined nonconscious mimicry among high and low
      self-monitors in situations varying in affiliative cues. Participants interacted
      with a confederate who shook her foot (Study 1) or touched her face (Study 2). In
      both studies, high self-monitors were more likely to mimic the confederate's
      subtle gestures when they believed the confederate to be a peer (Study 1) or
      someone superior to them (Study 2). Low self-monitors mimicked to the same degree
      across conditions. Thus, when the situation contains affiliative cues, high self
      monitors use mimicry as a nonconscious strategy to get along with their
      interaction partner.

PMID- 14674823
TI  - Method-specific variance in the implicit association test.
AB  - The Implicit Association Test (IAT; A. G. Greenwald, D. E. McGhee, & J. L. K.
      Schwartz, 1998) can be used to assess interindividual differences in the strength
      of associative links between representational structures such as attitude objects
      and evaluations. Four experiments are reported that explore the extent of method
      specific variance in the IAT. The most important findings are that conventionally
      scored IAT effects contain reliable interindividual differences that are method
      specific but independent of the measures' content, and that IAT effects can be
      obtained in the absence of a preexisting association between the response
      categories. Several techniques to decrease the impact of method-specific variance
      are evaluated. The best results were obtained with the D measures recently
      proposed by A. G. Greenwald, B. A. Nosek, and M. R. Banaji (2003).

PMID- 14674824
TI  - To do or to have? That is the question.
AB  - Do experiences make people happier than material possessions? In two surveys,
      respondents from various demographic groups indicated that experiential purchases
      those made with the primary intention of acquiring a life experience--made them
      happier than material purchases. In a follow-up laboratory experiment,
      participants experienced more positive feelings after pondering an experiential
      purchase than after pondering a material purchase. In another experiment,
      participants were more likely to anticipate that experiences would make them
      happier than material possessions after adopting a temporally distant, versus a
      temporally proximate, perspective. The discussion focuses on evidence that
      experiences make people happier because they are more open to positive
      reinterpretations, are a more meaningful part of one's identity, and contribute
      more to successful social relationships.

PMID- 14674826
TI  - Affect and face perception: odors modulate the recognition advantage of happy
      faces.
AB  - Previous choice reaction time studies have provided consistent evidence for
      faster recognition of positive (e.g., happy) than negative (e.g., disgusted)
      facial expressions. A predominance of positive emotions in normal contexts may
      partly explain this effect. The present study used pleasant and unpleasant odors
      to test whether emotional context affects the happy face advantage. Results from
      2 experiments indicated that happiness was recognized faster than disgust in a
      pleasant context, but this advantage disappeared in an unpleasant context because
      of the slow recognition of happy faces. Odors may modulate the functioning of
      those emotion-related brain structures that participate in the formation of the
      perceptual representations of the facial expressions and in the generation of the
      conceptual knowledge associated with the signaled emotion.

PMID- 14674827
TI  - Modulation of focused attention by faces expressing emotion: evidence from
      flanker tasks.
AB  - Three experiments evaluated whether facial expression can modulate the allocation
      of focused attention. Identification of emotionally expressive target faces was
      typically faster when they were flanked by identical (compatible) faces compared
      with when they were flanked by different (incompatible) faces. This flanker
      compatibility effect was significantly smaller when target faces expressed
      negative compared with positive emotion (see Experiment 1A); however, when the
      faces were altered to disrupt emotional expression, yet retain feature
      differences, equal flanker compatibility effects were observed (see Experiment
      1B). The flanker-compatibility effect was also found to be smaller for negative
      target faces compared compatibility with neutral target faces, and for both
      negative and neutral target faces compared with positive target faces (see
      Experiment 2). These results suggest that the constriction of attention is
      influenced by facial expressions of emotion.

PMID- 14674828
TI  - Modeling affective processes in dyadic relations via dynamic factor analysis.
AB  - An intraindividual variability design, including application of dynamic factor
      models, was used to examine the affective processes of a husband-wife dyad over
      182 consecutive days. Structural equation analyses indicated differences in the
      affective structure between the husband and the wife, and these differences were
      characterized in terms of their factorial configuration and temporal
      organization. Examination of the dyad's affective dynamics revealed
      unidirectional (i.e., from the husband to the wife) interpersonal influences with
      a defined structure over time.

PMID- 14674829
TI  - Is attention to feelings beneficial or detrimental to affective well-being? Mood
      regulation as a moderator variable.
AB  - This research examined the functionality of attention to feelings for affective
      well-being. The authors found that mood regulation, but not clarity of feelings,
      moderated the attention-well-being relationship. For individuals with high mood
      regulation scores, attention was beneficial to affective well-being, whereas for
      individuals with low mood regulation scores, attention was detrimental to
      affective well-being. This finding was corroborated by self- and peer reports in
      Study 1 and replicated in Study 2. The validity of the scales was established by
      the convergence of self- and peer ratings. Moreover, Study 2 showed that
      dysfunctional and functional and self consciousness scales suppressed variance in
      attention to feelings, thereby revealing that attention incorporates both
      adaptive and maladaptive aspects.

PMID- 14674830
TI  - Effect of negative emotional content on working memory and long-term memory.
AB  - In long-term memory, negative information is better remembered than neutral
      information. Differences in processes important to working memory may contribute
      to this emotional memory enhancement. To examine the effect that the emotional
      content of stimuli has on working memory performance, the authors asked
      participants to perform working memory tasks with negative and neutral stimuli.
      Task accuracy was unaffected by the emotional content of the stimuli. Reaction
      times also did not differ for negative relative to neutral words, but on an n
      back task using faces, participants were slower to respond to fearful faces than
      to neutral faces. These results suggest that although emotional content does not
      have a robust effect on working memory, in some instances emotional salience can
      impede working memory performance.

PMID- 14674831
TI  - Making sense of self-conscious emotion: linking theory of mind and emotion in
      children with autism.
AB  - Self-conscious emotions such as embarrassment and shame are associated with 2
      aspects of theory of mind (ToM): (a) the ability to understand that behavior has
      social consequences in the eyes of others and (b) an understanding of social
      norms violations. The present study aimed to link ToM with the recognition of
      self-conscious emotion. Children with and without autism identified facial
      expressions conscious of self-conscious and non-self-conscious emotions from
      photographs. ToM was also measured. Children with autism performed more poorly
      than comparison children at identifying self-conscious emotions, though they did
      not differ in the recognition of non-self-conscious emotions. When ToM ability
      was statistically controlled, group differences in the recognition of self
      conscious emotion disappeared. Discussion focused on the links between ToM and
      self-conscious emotion.

PMID- 14674832
TI  - Frontal electroencephalogram alpha asymmetry during sleep: stability and its
      relation to affective style.
AB  - Electroencephalogram (EEG) alpha (8-12 Hz) asymmetries were collected from the
      mid-frontal and central regions during presleep wakefulness and Stage 1, Stage 2,
      and rapid eye movement (REM) sleep in 11 healthy right-handed participants who
      were free of psychiatric, neurological, and sleep problems. The authors found
      significant correlations between presleep wakefulness and different stages of
      sleep in the frontal, but not central, EEG alpha asymmetry measure. The strongest
      correlation was between presleep waking and REM sleep, replicating and extending
      relation earlier work to a normal population. The high degree of association
      between presleep waking and REM sleep may be a result of high cortical activation
      common to these states and may reflect a predisposition to different styles of
      emotional reactivity.

PMID- 14674833
TI  - Sex-steroid derived compounds induce sex-specific effects on autonomic nervous
      system function in humans.
AB  - The physiological and psychological effects of 2 human sex-steroid derived
      compounds, 4.16-androstadien-3-one (AND) and l,3,5(10),16-estratetraen-3-ol(EST)
      were measured in 24 subjects who participated in a within-subjects, double-blind
      experiment. A dissociation was evident in the physiological effects of AND, in
      that it increased physiological arousal in women but decreased it in men. EST did
      not significantly affect physiological arousal in women or men. Neither compound
      significantly affected mood. AND is an androgen derivative that is the most
      prevalent androstene in human male sweat, male axillary hair, and on the male
      axillary skin surface. The authors argue that AND's opposite effects on
      physiology in men and women further implicate this compound in chemical
      communication between humans.

PMID- 14674834
TI  - Assessment of olfactory function and androstenone odor thresholds in humans with
      or without functional occlusion of the vomeronasal duct.
AB  - To obtain information on the possible role of the vomeronasal duct (VND) in odor
      perception and human pheromone detection, the present study investigated
      different aspects of olfactory function, including thresholds for androstenone in
      adults with or without detectable VNDs. The study also examined correlations
      between detection thresholds of androstenone odor and general olfactory function.
      Subjects' olfaction was assessed with tests for odor identification, odor
      discrimination, and phenyl ethyl alcohol odor threshold. Measurements were
      performed on 1 side only, with and without covering the VND. Subjects with or
      without detectable VNDs did not differ in olfactory sensitivity or androstenone
      odor thresholds. A small but significant correlation was found between detection
      thresholds of androstenone and general olfactory function. Finally, covering of
      the VND did not affect olfactory function or androstenone sensitivity. Results
      suggest that the human VND does not play a major role in sensitivity toward
      odorants or the perception of androstenone.

PMID- 14674835
TI  - Olfactory sensitivity for aliphatic esters in spider monkeys (Ateles geoffroyi).
AB  - Using a conditioning paradigm, the authors investigated the olfactory sensitivity
      of 3 spider monkeys (Ateles geoffroyi) for a homologous series of aliphatic
      esters (ethyl acetate to n-octyl acetate) and isomeric forms of some of these
      substances. With all odorants, the monkeys significantly discriminated
      concentrations below 1 ppm from the odorless solvent, and in several cases,
      individual monkeys even demonstrated thresholds below 1 ppb. The results showed
      spider monkeys to have a high olfactory sensitivity for aliphatic esters, which
      for the majority of substances matches or even is better than that of species
      such as the rat, the mouse, or the dog. These findings support the assumption
      that between-species comparisons of neuroanatomical features are poor predictors
      of olfactory performance.

PMID- 14674836
TI  - Differential associations between entorhinal and hippocampal volumes and memory
      performance in older adults.
AB  - Magnetic resonance imaging-derived entorhinal and hippocampal volumes were
      measured in 14 nondemented, community-dwelling older adults. Participants were
      selected so that memory scores from 2 years prior to scanning varied widely but
      were not deficient relative to age-appropriate norms. A median split of these
      memory scores defined high-memory and low-memory groups. Verbal memory scores at
      the time of imaging were lower, and entorhinal and hippocampal volumes were
      smaller, in the low-memory group than in the high-memory group. Left entorhinal
      cortex volume showed the strongest correlation (r= .79) with immediate recall of
      word lists. Left hippocampal volume showed the strongest correlation (r= .57)
      with delayed paragraph recall. These results suggest that entorhinal and
      hippocampal volumes are related to individual differences in dissociable kinds of
      memory performance among healthy older adults.

PMID- 14674837
TI  - Evaluating self-generated information: anterior prefrontal contributions to human
      cognition.
AB  - The anterior or rostrolateral prefrontal cortex (RLPFC) is frequently recruited
      during complex cognitive tasks across a wide range of domains, including
      reasoning, long-term memory retrieval, and working memory. The authors report an
      event-related functional MRI study, indicating that the RLPFC is specifically
      involved in the evaluation of internally generated information--or information
      that cannot be readily perceived from the external environment but has to be
      inferred or self-generated. The findings are consistent with a hierarchical model
      of lateral prefrontal organization, with RLPFC contributing only at the highest
      orders of cognitive transformations. This characterization of RLPFC function may
      help explain seemingly disparate findings across multiple cognitive domains and
      could provide a unified account of this region's contribution to human cognition.

PMID- 14674838
TI  - Hypertension and the brain: vulnerability of the prefrontal regions and executive
      functions.
AB  - Untreated hypertension negatively affects brain anatomy and cognitive functions,
      but the effects of medically treated hypertension are unclear. The authors
      compared 40 middle-age and older adults diagnosed with essential hypertension to
      demographically matched normotensive peers. Volumes of 7 brain regions and deep
      and periventricular white-matter hyperintensities (WMH) were measured on magnetic
      resonance imaging scans. Performance in 4 cognitive domains (perseveration,
      working memory, fluid reasoning, and vocabulary knowledge) was evaluated. Persons
      with hypertension had smaller prefrontal cortex and underlying white matter
      volumes and increased frontal WMH. No group differences were found in other
      examined brain regions. Among examined cognitive variables, hypertensive patients
      committed significantly more perseverative errors. Thus, even controlled
      hypertension may be associated with deficits in brain structure and cognition,
      warranting further study.

PMID- 14674839
TI  - Conditional discrimination learning in patients with bilateral medial temporal
      lobe amnesia.
AB  - The ability of bilateral medial temporal lobe amnesic patients (MT; n=8) and
      normal participants (NC; n=8) to acquire a conditional discrimination in trace
      and delay eyeblink conditioning paradigms was investigated. Experiment 1 assessed
      trace conditional discrimination learning by using a light conditional stimulus
      (S+/S-) and tone conditioned stimulus (CS) separated by a 1-s trace. NCs
      responded differentially on S+ trials (mean percent conditioned responses=66)
      versus S- trials (30). Whereas MTs were impaired in their acquisition of the
      conditional discrimination (S+ =51, S- =43). In Experiment 2, the temporal
      separation was eliminated. NCs acquired the conditional discrimination (S+ =70, S
      =29). MTs were unable to respond differentially (S+ =42, S- =37). The findings
      indicate that the hippocampal system is essential in acquiring a conditional
      discrimination, even in a delay paradigm.

PMID- 14674840
TI  - The ontogeny of human learning in delay, long-delay, and trace eyeblink
      conditioning.
AB  - The ontogeny of associative learning in delay (750-ms conditional stimulus [CS],
      650-ms interstimulus interval [ISI]), long-delay (1,350-ms CS, 1,250-ms ISI), and
      trace (750-ms CS, 500-ms trace interval, 1,250-ms ISI) eyeblink conditioning was
      examined in 5-month-old human infants and adults. Infants and adults showed
      different acquisition rates but reached equivalent asymptotes of conditional
      responses (CRs) in standard delay conditioning. In long-delay and trace
      conditions, infants exhibited less robust conditioning than adults and minimal
      ability to appropriately time CRs. During infancy, the ISI, rather than the
      conditioning procedure, predicted rate and effectiveness of CRs. These findings
      suggest that higher order cognitive abilities begin emerging early in
      development. Across ontogeny, however, there are changes in the limits and
      parameters that support associative learning.

PMID- 14674841
TI  - Cerebellar neuronal activity expresses the complex topography of conditioned
      eyeblink responses.
AB  - Pavlovian eyeblink conditioning is a useful model system for studying how the
      temporal relationship between a conditioned stimulus and an unconditioned
      stimulus is represented in the brain. As an example, the response topography
      formed under a complex conditioning paradigm, involving 2 randomly alternating
      interstimulus intervals (ISIs), manifests a conditioned response (CR) with 2
      distinctive peaks that correspond to the 2 ISIs. The authors present the first
      full report of neuronal activities in the cerebellar interpositus nucleus of
      rabbits performing bimodal responses. All CR-related activities exhibited firing
      patterns that highly correlated with and preceded eyeblink responses. The
      striking similarity between the time course of bimodal CRs and neuronal responses
      indicates that neuronal activities in the cerebellum are causally related to the
      production of behavioral CRs.

PMID- 14674842
TI  - Cholesterol modifies classical conditioning of the rabbit (Oryctolagus cuniculus)
      nictitating membrane response.
AB  - Cholesterol plays an important role in synapse formation, receptor function, and
      synaptic plasticity, and animal studies show that modifying cholesterol may
      improve learning and memory. Other data show that feeding animals cholesterol can
      induce beta amyloid accumulation. Rabbits (Oryctolagus cuniculus) fed 2%
      cholesterol for 8 weeks were given trace conditioning of the nictitating membrane
      response using a 100-ms tone, a 700-ms trace, and periorbital electrical
      stimulation or airpuff. Rabbits fed cholesterol showed significant facilitation
      of trace conditioning to airpuff and conditioning-specific reflex modification to
      periorbital electrical stimulation and airpuff. The cholesterol-fed rabbits had
      beta amyloid accumulation in the cortex, but little in the hippocampus. The data
      suggest cholesterol had facilitative effects that outweighed potential amnesic
      effects of cortical beta amyloid.

PMID- 14674843
TI  - Exploratory activity and fear conditioning abnormalities develop early in R6/2
      Huntington's disease transgenic mice.
AB  - The Huntington's disease R6/2 transgenic mouse model, containing exon 1 of the
      human huntingtin gene with a greatly increased CAG repeat length, shows multiple
      effects of the altered polyglutamine in the resultant protein. The authors report
      that exploratory and fear conditioning behavioral changes appear well before the
      onset of obvious pathology. The first differences in exploratory and fear
      conditioning behavior emerge by 4 and 5 weeks of age, respectively. These
      behaviors correlate with the earliest neurochemical and molecular changes
      previously reported and provide insight into functional mechanisms by which
      cellular and subcellular disease changes may mediate neurological symptoms. These
      studies provide behavioral protocols suitable for high-throughput screening of
      therapeutic agents.

PMID- 14674844
TI  - Patterns of brain activity associated with variation in voluntary wheel-running
      behavior.
AB  - Rodents spontaneously run on wheels, but what underlies variation within and
      between species is unknown. This study used Fos immunoreactivity to compare brain
      activity in mice selectively bred for high wheel running (S) versus control (C)
      mice. Mice ran for 6 days, but on Day 7, half the mice were prevented from
      running. A strong positive correlation was found between running distance and Fos
      in the dentate gyrus of C runners that was lost in S runners. In mice prevented
      from running, Fos was higher in S than in C in the lateral hypothalamus, medial
      frontal cortex, and striatum. Results implicate specific brain regions in
      motivation to run and others in control of the intensity of the locomotor
      behavior itself.

PMID- 14674845
TI  - Behavioral phenotype of the reeler mutant mouse: effects of RELN gene dosage and
      social isolation.
AB  - Reeler (rl/rl) and reeler/wild-type (+/rl) mice synthesize Reln at subnormal
      rates, as do patients with schizophrenia, bipolar disorder, and autism, thereby
      forming the basis for a Reln hypothesis for vulnerability to these
      psychopathologies and justifying attention to the behavioral phenotypes of Reln
      deficient mice. Tests of gait, emotionality, social aggression, spatial working
      memory, novel-object detection, fear conditioning, and sensorimotor reflex
      modulation revealed the behavioral phenotype of rl/rl, but not +/rl, mice to be
      different from that of wild-type (+/+) mice. These results reveal no effect of
      Reln gene dosage and provide significant challenges to both the Reln and the
      neurodevelopmental hypotheses of the etiology of major psychopathologies.

PMID- 14674846
TI  - Nicotine enhances contextual fear conditioning and ameliorates ethanol-induced
      deficits in contextual fear conditioning.
AB  - Nicotine and ethanol are 2 commonly used and abused drugs that have divergent
      effects on learning. The present study examined the effects of acute nicotine
      (0.25 mg/kg), ethanol (1.0 g/kg), and ethanol-nicotine coadministration on fear
      conditioning in C57BL/6 mice. Mice were assessed for contextual and cued fear
      conditioning at 1 day and 1 week posttraining. Ethanol disrupted acquisition but
      not consolidation of contextual fear conditioning; nicotine enhanced contextual
      fear conditioning and ameliorated ethanol-associated deficits in contextual fear
      conditioning. Mecamylamine antagonized this effect. Fear conditioning was
      reassessed 1 week after initial testing with no drug administered. At the 1-week
      retest, mice previously treated with nicotine continued to show enhanced
      contextual fear, and mice previously treated with ethanol continued to show
      contextual fear deficits. Thus, nicotine both produces a long-lasting enhancement
      of contextual fear conditioning and protects against ethanol-associated deficits.

PMID- 14674847
TI  - Sex differences in the behavioral response to spatial and object novelty in adult
      C57BL/6 mice.
AB  - The present studies examined sex differences in object localization and
      recognition in C57BL/6 mice. Experiment 1 measured responses to spatial novelty
      (object displacement) and object novelty (object substitution). Males strongly
      preferred displaced and substituted objects over unchanged objects, whereas
      females showed a preference in only 1 measure of object novelty. Experiment 2
      further examined object recognition by presenting mice with 2 identical objects,
      followed 24 hr or 7 days later by testing with a familiar and a novel object.
      After 24 hr, males preferentially explored the novel object, whereas females
      exhibited no such preference. Neither sex displayed a preference for the novel
      object after 7 days. The data suggest that male mice are superior to females at
      localizing and recognizing objects.

PMID- 14674848
TI  - Opioid receptors regulate the extinction of Pavlovian fear conditioning.
AB  - Rats received a single pairing of an auditory conditioned stimulus (CS) with a
      footshock unconditioned stimulus (US). The fear (freezing) that had accrued to
      the CS was then extinguished. Injection of naloxone prior to this extinction
      significantly impaired the development of extinction. This impairment was
      mediated by opioid receptors in the brain and was not observed when naloxone was
      injected after extinction training. Finally, an injection of naloxone on test
      failed to reinstate extinguished responding that had already accrued to the CS.
      These experiments show that opioid receptors regulate the development, but not
      the expression, of fear extinction and are discussed with reference to the roles
      of opioid receptors in US processing, memory, and appetitive motivation.

PMID- 14674849
TI  - Inhibitory control in rats performing a stop-signal reaction-time task: effects
      of lesions of the medial striatum and d-amphetamine.
AB  - The stop-signal task measures the ability to inhibit a response that has already
      been initiated, that is, the ability to stop. Imaging studies have implicated
      frontostriatal circuitry in the mediation of this form of response control. The
      authors report inhibition functions of normal rats and those with medial striatal
      damage performing the stop-signal task. Excitotoxic lesions of the medial
      striatum produced significant deficits on task performance, including increased
      omissions on the go task and flattened inhibition function, possibly as a result
      of increased reaction-time mean and variability. Medial striatal lesions also
      significantly slowed stop-signal reaction time. Subsequent treatment with d
      amphetamine removed (0.3 mg/kg) or exacerbated (1.0 mg/kg) this deficit.

PMID- 14674850
TI  - The role of perirhinal cortex in visual discrimination learning for visual
      secondary reinforcement in rats.
AB  - Perirhinal cortex in monkeys has been thought to be involved in visual
      associative learning. The authors examined rats' ability to make associations
      between visual stimuli in a visual secondary reinforcement task. Rats learned 2
      choice visual discriminations for secondary visual reinforcement. They showed
      significant learning of discriminations before any primary reinforcement.
      Following bilateral perirhinal cortex lesions, rats continued to learn visual
      discriminations for visual secondary reinforcement at the same rate as before
      surgery. Thus, this study does not support a critical role of perirhinal cortex
      in learning for visual secondary reinforcement. Contrasting this result with
      other positive results, the authors suggest that the role of perirhinal cortex is
      in "within-object" associations and that it plays a much lesser role in stimulus
      stimulus associations between objects.

PMID- 14674851
TI  - Perirhinal cortex and anterior thalamic lesions: comparative effects on learning
      and memory.
AB  - Three learning and memory tasks were used to compare the effects of neurotoxic
      anterior thalamic nuclei (ATN) and perirhinal cortex (PRC) lesions in rats. Rats
      with ATN lesions showed impaired spatial memory in a 12-arm radial maze, whereas
      rats with PRC lesions showed intact spatial memory, despite the use of minimal
      pretraining and extensive within-session delays (to 40 rain). PRC, but not ATN,
      lesions produced impairments on a configural learning task using complex visual
      tactile cues in the radial maze. Neither ATN nor PRC lesions consistently
      affected spontaneous object recognition across extended sample-test delays (to 40
      min). These findings confirm the differential involvement of the ATN and PRC in
      learning and memory.

PMID- 14674852
TI  - Transfer effects and conditional learning in rats with selective lesions of
      medial septal/diagonal band cholinergic neurons.
AB  - The authors examined visual-spatial conditional learning with automated
      touchscreen tasks in male Long-Evans rats with selective lesions of medial
      septal/vertical limb of diagonal band (MS/VDB) cholinergic neurons produced by
      192 IgG-saporin. Performance on a conditional task, in which 1 of 2 centrally
      displayed stimuli directed the rat to respond to an illuminated panel on the left
      or right, depended on training history: Control rats with experience on other
      visual tasks performed better than MS/VDB-lesioned rats with similar training
      histories, whereas this effect was reversed in naive rats. This difference
      appears to reflect transfer effects present in the control rats that are absent
      in the MS/VDB-lesioned rats. These findings may suggest that MS/VDB cholinergic
      neurons play a particular role in the transfer of behavioral experience and
      flexibility of application of behavioral rules in memory, rather than a role in
      conditional learning per se.

PMID- 14674853
TI  - Impaired performance of fornix-transected rats on a distal, but not on a
      proximal, version of the radial-arm maze cue task.
AB  - Fornix-transected and sham-operated rats were trained on radial maze cue tasks in
      which the relative positions of the cues were either fixed (F condition) or
      varied (V condition) across trials. Proximal and distal visual stimuli were used
      in 2 different experiments. With proximal stimuli, fornix-transected rats were
      transiently impaired in the V condition and performed as well as controls in the
      F condition. However, using extramaze stimuli, fornix-transected rats were
      severely impaired in the V condition but performed normally in the F condition.
      According to histological analyses, performance on these cue tasks varied along
      with the extent of cholinergic depletion in the hippocampus. At the behavioral
      level, the location and stability of stimuli's relative positions seemed to have
      influenced rats' performance.

PMID- 14674854
TI  - Using idiothetic cues to swim a path with a fixed trajectory and distance:
      necessary involvement of the hippocampus, but not the retrosplenial cortex.
AB  - Rats rapidly learned to find a submerged platform in a water maze at a constant
      distance and angle from the start point, which changed on every trial. The rats
      performed accurately in the light and dark, but prior rotation disrupted the
      latter condition. The rats were then retested after receiving cytotoxic
      hippocampal or retrosplenial cortex lesions. Retrosplenial lesions had no
      apparent effect in either the light or dark. Hippocampal lesions impaired
      performance in both conditions but spared the ability to locate a platform placed
      in the center of the pool. A hippocampal deficit emerged when this pool-center
      task was run in the dark. The spatial effects of hippocampal damage extend beyond
      allocentric tasks to include aspects of idiothetic guidance.

PMID- 14674855
TI  - Deficient spatial memory induced by blockade of beta-adrenoceptors in the
      hippocampal CA1 region.
AB  - A previous study showed that intra-CAl infusion of the beta-adrenergic antagonist
      DL-propranolol interfered with consolidation of memory for contextual fear
      conditioning (J.-Z. Ji, X.-M. Wang, & B.-M. Li, 2003). The present study
      investigated the effect of similarly administered DL-propranolol on consolidation
      of spatial memory for the water maze. DL-propranolol infused 5 min, but not 6 hr,
      posttraining caused a deficit in 48-hr memory for the spatial water maze task,
      whereas similarly administered D-propranolol, which has an equipotent "local
      anesthetic" activity but significantly lower beta-blocking activity, induced no
      amnesia. However, DL-propranolol administered 5 min posttraining did not impair
      48-hr memory for the cued water maze task. Thus, beta-adrenoceptor in area CA1 is
      involved in regulating consolidation of spatial memory for the water maze.

PMID- 14674856
TI  - Localization of function within the dorsal hippocampus: the role of the CA3
      subregion in paired-associate learning.
AB  - Computational models and electrophysiological data suggest that the CA3 subregion
      of the hippocampus supports the formation of arbitrary associations; however, no
      behavioral studies have been conducted to test this hypothesis. Rats with
      neurotoxin-induced lesions of dorsal dentate gyrus (DG), CA3, or CA1 were tested
      on object-place and odor-place paired-associate tasks to test whether the
      mechanism that supports paired-associate learning is localized to the CA3
      subregion of the dorsal hippocampus or whether all hippocampal subregions
      contribute to paired-associate learning. The data indicate that rats with DG or
      CA1 lesions learned the tasks as well as controls; however, CA3-lesioned rats
      were impaired in learning the tasks. Thus, the CA3 subregion of the dorsal
      hippocampus contains a mechanism to support paired-associate learning.

PMID- 14674857
TI  - Ovarian hormones and cognition in the aged female rat: I. Long-term, but not
      short-term, ovariectomy enhances spatial performance.
AB  - Although research suggests that ovariectomy (ovx) is detrimental to spatial
      cognition in young rats, little work has evaluated the cognitive effects of ovx
      in aged rats. The authors investigated the effects of ovx in aged rats using the
      water radial-arm maze. In Study 1, young rats and aged rats receiving ovx 1.5
      months before testing outperformed aged rats receiving sham surgery or ovx 21
      days before testing. In Study 2, young rats and aged rats receiving ovx 2.0 or
      6.0 months before testing outperformed aged sham rats. Aged rats exhibited
      estradiol and elevated progesterone levels comparable to those of young rats. The
      findings suggest that 1.5-6.0 months, but not 21 days, of ovx improves spatial
      memory in aged rats. The hypothesis that long-term ovarian hormone loss is
      detrimental to spatial memory in aged rats was not supported. The authors
      hypothesize that removal of elevated progesterone levels is related to the ovx
      induced cognitive enhancement.

PMID- 14674858
TI  - Castration reduces the effect of serotonin-1A receptor stimulation on prepulse
      inhibition in rats.
AB  - This study examined the interaction between hormones and serotonin-1A (5-HT1A)
      receptor modulation of prepulse inhibition (PPI) of the acoustic startle
      response. Male and female rats were gonadectomized; some castrated rats received
      testosterone- or estrogen-filled implants. Rats were randomly injected with
      saline or 0.02 or 0.50 mg/kg 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT),
      a selective 5-HT1A receptor agonist. All rats showed a dose-dependent disruption
      of PPI in response to 8-OH-DPAT. In untreated castrated rats, this disruption was
      significantly reduced (33% compared with 78% in sham-operated rats). Testosterone
      treatment reversed this reduction, but estrogen was less effective.
      Ovariectomized and sham-operated rats showed similar PPI in response to 8-OH
      DPAT. These data suggest that the effect of 8-OH-DPAT on PPI in male rats depends
      on circulating hormone levels, particularly testosterone.

PMID- 14674859
TI  - Novel tastes elevate c-fos expression in the central amygdala and insular cortex:
      implication for taste aversion learning.
AB  - Taste novelty strongly modulates the speed and strength of taste aversion
      conditioning. To identify molecular signals responsive to novel tastes,
      immunostaining for c-fos protein (Fos-like immunoreactivity [FLI]) was used to
      mark neurons that responded differentially to taste novelty. Novel saccharin
      induced larger increases in FLI than familiar saccharin. This pattern was seen in
      central amygdala and insular cortex, but not in basolateral amygdala,
      parabrachial nucleus, or nucleus of the solitary tract. Other parameters known to
      influence aversion learning were tested for effects on FLI. Manipulations known
      to reduce the strength of learning blunted the FLI response, supporting the idea
      that FLI marks neural pathways critical to taste processing during acquisition,
      and that c-fos expression is a key transcriptional event underlying this
      plasticity.

PMID- 14674860
TI  - Temporal coding of sensation: mimicking taste quality with electrical stimulation
      of the brain.
AB  - Two experiments suggested that the temporal pattern of a taste response in the
      brain can convey meaningful information. In Experiment 1, rats avoided lick
      contingent electrical stimulation of the nucleus of the solitary tract (NTS; the
      first synaptic relay for taste) when the temporal pattern of pulses mimicked the
      electrophysiological response to quinine, but not when the temporal pattern was
      randomized. In Experiment 2, rats avoided lick-contingent electrical stimulation
      of the NTS that mimicked the temporal pattern of a sucrose response following
      stimulation-illness pairings. This aversion generalized to sucrose but not to the
      other tastants; extinction of the aversion to electrical stimulation also
      extinguished the aversion to sucrose. Results replicate and extend previous
      findings (P. M. Di Lorenzo & G. S. Hecht, 1993).

PMID- 14674861
TI  - Intensity modulation of olfactory acuity.
AB  - Acuity is fundamental to sensory systems, establishing the foundation for
      detectable differences in stimulus quality and consequently shaping animals'
      sensory capacities. In the olfactory system, which samples intrinsically high
      dimensional chemical information, acuity for odor quality is measurable by means
      of ad hoc dimensions based on behaviorally confirmed sets of sequentially similar
      odorants. The authors measure olfactory acuity in mice using a rewarded forced
      choice odor generalization task and show that mice exhibit greater olfactory
      acuity in response to higher concentration (1,0 Pa) odorants than to lower
      concentration (0.01 Pa) odorants. Results suggest that the dynamic modulation of
      sensory acuity--not necessarily its maximization--is an important component of
      olfactory processing and reflects the salience of odorant stimuli.

PMID- 14674862
TI  - Impairments in spatial generalization of visual skills after V4 and TEO lesions
      in macaques (Macaca mulatta).
AB  - The authors tested the spatial generalization of shape and color discriminations
      in 2 monkeys, in which 3 visual field quadrants were affected, respectively, by
      lesions in area V4, TEO, or both areas combined. The fourth quadrant served as a
      normal control. The monkeys were trained to discriminate stimuli presented in a
      standard location in each quadrant, followed by tests of discrimination
      performance in new locations in the same quadrant. In the quadrant affected by
      the V4 + TEO lesion, the authors found temporary but striking deficits in spatial
      generalization of shape and color discriminations over small distances,
      suggesting a contribution of areas V4 and TEO to short-range spatial
      generalization of visual skills.

PMID- 14674863
TI  - Opposite turning behavior in right-handers and non-right-handers suggests a link
      between handedness and cerebral dopamine asymmetries.
AB  - The strong right hand preference in humans remains a riddle; no lateralized
      behavior other than fine finger dexterity relates to it. The relation between
      handedness and language dominance may be far weaker than currently judged; after
      all, both right-handers and non-right-handers utilize the left brain for speech.
      There is, however, a lateralized motor preference in animals, turning behavior,
      that is strongly associated with hemispheric dopamine (DA) asymmetries. Turning
      consistently occurs towards the side with less DA. The authors tested 69 right
      handers and 24 non-right-handers with a device recording spontaneous turning
      behavior for 20 hr within 3 days. Findings indicate that right-handers preferred
      left-sided turning and non-right-handers preferred right-sided turning. This
      result suggests a link between handedness and DA asymmetries.

PMID- 14674864
TI  - Glucocorticoid receptor agonist enhances pavlovian appetitive conditioning but
      disrupts outcome-specific associations.
AB  - A Pavlovian-instrumental transfer design was used to investigate the impact of
      the glucocorticoid receptor agonist dexamethasone (dex) on Pavlovian associations
      involving the sensory and motivational aspects of rewards. Rats were trained with
      2 lever responses, R1 and R2, for different rewards, Outcome (O)1 and O2. In
      separate Pavlovian training sessions. Stimulus A was paired with O1 and Stimulus
      B with O2. Administration of dex after A-O1 sessions enhanced A-O1 associations
      measured in extinction, relative to B-O2 pairings that were followed by saline.
      In lever-press transfer tests, presentation of Stimuli A or B enhanced general
      responding to the same degree. However, outcome-specific transfer (selectively
      greater enhancement of R1 during A and R2 during B) was abolished for Stimulus A.
      This suggests that memory enhancement by posttraining dex is simultaneously
      detrimental to processing of outcome-specific sensory information.

PMID- 14674865
TI  - High illumination levels potentiate the acoustic startle response in preweanling
      rats.
AB  - Fear potentiation of the acoustic startle response (FPS) by aversive conditioned
      stimuli does not emerge in rats until Postnatal Day (P)23 (see P. S. Hunt & B. A.
      Campbell, 1997). However, the present study found that when presented with an
      unconditioned fear-eliciting stimulus, rats younger than P23 display FPS.
      Specifically, high illumination levels were found to enhance startle amplitudes
      in rats aged 18 and 25 days, but not 14 days. Furthermore, the light-enhanced
      startle observed in P18 rats was prevented by a systemic injection of the
      noradrenergic beta-receptor antagonist propranolol. These data suggest that
      conditioned and unconditioned FPS have different ontogenetic trajectories, and
      thereby provide support for the idea that learned and unlearned fear are
      subserved by dissociable neural systems.

PMID- 14674866
TI  - Introduction to the special section on structural equation modeling.
AB  - Structural equation modeling (SEM) is a frequently used data-analytic technique
      in psychopathology research. This popularity is due to the unique capabilities
      and broad applicability of SEM and to recent advances in model and software
      development. Unfortunately, the popularity and accessibility of SEM is matched by
      its complexities and ambiguities. Thus, users are often faced with difficult
      decisions regarding a variety of issues. This special section is designed to
      increase the effective use of SEM by reviewing recently developed modeling
      capabilities, identifying common problems in application, and recommending
      appropriate strategies for analysis and evaluation.

PMID- 14674867
TI  - The use of latent trajectory models in psychopathology research.
AB  - Despite the recent surge in the development of powerful modeling strategies to
      test questions about individual differences in stability and change over time,
      these methods are not currently widely used in psychopathology research. In an
      attempt to further the dissemination of these new methods, the authors present a
      pedagogical introduction to the structural equation modeling based latent
      trajectory model, or LTM. They review several different types of LTMs, discuss
      matching an optimal LTM to a given question of interest, and highlight several
      issues that might be particularly salient for research in psychopathology. The
      authors augment each section with a review of published applications of these
      methods in psychopathology-related research to demonstrate the implementation and
      interpretation of LTMs in practice.

PMID- 14674868
TI  - Missing data techniques for structural equation modeling.
AB  - As with other statistical methods, missing data often create major problems for
      the estimation of structural equation models (SEMs). Conventional methods such as
      listwise or pairwise deletion generally do a poor job of using all the available
      information. However, structural equation modelers are fortunate that many
      programs for estimating SEMs now have maximum likelihood methods for handling
      missing data in an optimal fashion. In addition to maximum likelihood, this
      article also discusses multiple imputation. This method has statistical
      properties that are almost as good as those for maximum likelihood and can be
      applied to a much wider array of models and estimation methods.

PMID- 14674869
TI  - Testing mediational models with longitudinal data: questions and tips in the use
      of structural equation modeling.
AB  - R. M. Baron and D. A. Kenny (1986; see record 1987-13085-001) provided clarion
      conceptual and methodological guidelines for testing mediational models with
      cross-sectional data. Graduating from cross-sectional to longitudinal designs
      enables researchers to make more rigorous inferences about the causal relations
      implied by such models. In this transition, misconceptions and erroneous
      assumptions are the norm. First, we describe some of the questions that arise
      (and misconceptions that sometimes emerge) in longitudinal tests of mediational
      models. We also provide a collection of tips for structural equation modeling
      (SEM) of mediational processes. Finally, we suggest a series of 5 steps when
      using SEM to test mediational processes in longitudinal designs: testing the
      measurement model, testing for added components, testing for omitted paths,
      testing the stationarity assumption, and estimating the mediational effects.

PMID- 14674870
TI  - Potential problems with "well fitting" models.
AB  - The assessment of model fit is a more complex and indeterminate process than is
      commonly acknowledged by researchers who use structural equation modeling (SEM)
      techniques. Even models that are well fitting according to commonly used
      statistical tests and descriptive fit indices can have significant problems and
      ambiguities. The authors discuss 7 potential difficulties that can arise and that
      should temper researchers' conclusions: equivalent models, nonequivalent but well
      fitting alternative models, omitted variables, problematic lower-order model
      components, the failure to parse composite models into meaningful partitions
      (e.g., measurement vs. structural), inattention to the multiple factors that
      affect the sensitivity of measures of fit to model misspecifications, and
      reliance on specification searches. In addition to providing examples of each of
      these problems, the authors offer recommendations for psychopathologists who
      conduct SEM analyses.

PMID- 14674871
TI  - Attributional biases in aggressive children and their mothers.
AB  - To investigate if mothers and their aggressive children share the tendency to
      infer hostile motives from others' behavior in ambiguous social situations, 100
      pairs of mothers and their clinic-referred or comparison children (50 boys and 50
      girls) were asked to interpret hypothetical situations involving both overtly and
      relationally provocative scenarios. Results replicated previous findings of
      studies on social information processing of aggressive children and extended the
      findings to mothers of aggressive children. Findings were generally consistent
      with the hypothesis that mothers of aggressive children tend to view others'
      ambiguous actions as hostile, increasing the probability of responding with
      aggression and, in effect, modeling a hostile attributional bias for their
      children. Examinations of mothers' and their children's attributional and
      behavioral intentions suggested that mothers' and daughters' attributions and
      behavioral intentions were significantly correlated, whereas mothers' and sons'
      were not. Gender effects with regard to provocation type are also discussed.

PMID- 14674872
TI  - Alcohol use disorders and psychological distress: a prospective state-trait
      analysis.
AB  - The present study examined the association between alcohol use disorders (AUDs)
      and psychological distress over an 11-year period using a sample of 378 young
      adults (46% men, 54% women: baseline age = 18.5; 51% with paternal history of
      alcoholism). The authors examined this relation using a state-trait model, which
      decomposes variance in a given construct into a general traitlike factor that
      spans measurement occasion and more situational, occasion-specific variability.
      Trait AUD and trait distress were correlated (r =.43), suggesting that the
      tendency to meet criteria for an AUD is associated with the tendency to
      experience psychological distress. Much of this association was due to 3rd
      variables (primarily neuroticism but also childhood stressors and behavioral
      undercontrol), supporting a common 3rd-variable influence model of comorbidity.

PMID- 14674873
TI  - Group comparisons of DSM-IV subtypes of chronic depression: validity of the
      distinctions, part 2.
AB  - The nosology of chronic depression in Diagnostic and Statistical Manual of Mental
      Disorders (4th ed.; DSM-IV, American Psychiatric Association, 1994) is highly
      complex and requires clinicians to differentiate among several chronic course
      subtypes. This study replicates an earlier investigation (J. McCullough et al.,
      2000; see record 2000-05424-007) that found few differences among Diagnostic and
      Statistical Manual of Mental Disorders (3rd ed. rev.; DSM-III-R; American
      Psychiatric Association, 1987) categories of chronic depression. In the present
      study, 681 outpatients with chronic major depression, double depression,
      recurrent major depression without full interepisode recovery, and chronic major
      depression superimposed on antecedent dysthymia were compared. Few differences
      were observed on a broad range of demographic, clinical, psychosocial, family
      history, and treatment response variables. The authors suggest that chronic
      depression should be viewed as a single, broad condition that can assume a
      variety of clinical course configurations.

PMID- 14674874
TI  - Lateralized lexical decision in schizophrenia: hemispheric specialization and
      interhemispheric lexicality priming.
AB  - Reports of left-hemisphere dysfunction and abnormal interhemispheric transfer in
      schizophrenia are mixed. The authors used a unified paradigm, the lateralized
      lexical decision task, to assess hemispheric specialization in word recognition,
      hemispheric error monitoring, and interhemispheric transfer in male, right-handed
      participants with schizophrenia (n=34) compared with controls (n=20). Overall,
      performance and error monitoring were worse in patients. However, patients like
      controls showed left-hemisphere superiority for lexical processing and right
      hemisphere superiority for error monitoring. Only patients showed selective
      interhemispheric lexicality priming for accuracy, in which performance improved
      when the lexical status of target and distractor stimuli presented to each
      hemifield was congruent. Results suggest that schizophrenia is associated with
      impaired monitoring and with increased interhemispheric automatic information
      transfer rather than with changed hemispheric specialization for language or
      error monitoring.

PMID- 14674875
TI  - A longitudinal latent variable analysis of reciprocal relations between
      depressive symptoms and delinquency during adolescence.
AB  - In this longitudinal study, reciprocal relations between depressive symptoms and
      delinquent behavior were examined for a sample of 1,218 male and female
      adolescents (mean age, 15.51 years at Time 1). Associations were examined within
      a latent variable approach, controlling for indicator-specific tendencies,
      students' age and parental education, time-specific 3rd-variable influences,
      level of prior problem behavior, and measurement error. Findings thus provided
      relatively unbiased estimates of existing plausible causal relations. Analyses
      revealed a relatively small unidirectional effect of delinquency on depression
      for boys (at 1 of 3 time points), and bidirectional effects of comparable size
      for girls. The circular process for the girls was explained drawing on gender
      socialization theory and theories of offending behavior. Implications for
      preventive interventions are also discussed.

PMID- 14674876
TI  - Epidemiology of trauma and posttraumatic stress disorder in Mexico.
AB  - Prevalence rates of trauma and posttraumatic stress disorder (PTSD) were
      estimated from a probability sample of 2,509 adults from 4 cities in Mexico. PTSD
      was assessed according to Diagnostic and Statistical Manual of Mental Disorders
      (American Psychiatric Association, 1994) criteria using the Composite
      International Diagnostic Interview (CIDI; WHO, 1997). Lifetime prevalence of
      exposure and PTSD were 76% and 11.2%, respectively. Risk for PTSD was highest in
      Oaxaca (the poorest city), persons of lower socioeconomic status, and women.
      Conditional risk for PTSD was highest following sexual violence, but nonsexual
      violence and traumatic bereavement had greater overall impact because of their
      frequency. Of lifetime cases, 62% became chronic; only 42% received medical or
      professional care. The research demonstrates the importance of expanding the
      epidemiologic research base on trauma to include developing countries around the
      world.

PMID- 14674877
TI  - A taxometric study of borderline personality disorder.
AB  - Taxometric methodology was used to determine whether borderline personality
      disorder (BPD) represents a taxon that is categorically distinct from normal
      personality or whether it falls on a dimensional continuum with normality. Two
      taxometric procedures were used with a sample of 1,389 outpatients assessed for
      BPD symptoms by semistructured interview. The procedures indicated that BPD does
      not represent a latent category. Implications are drawn for the conceptualization
      and etiology of BPD, and for the categorical versus dimensional status of
      personality disorders in general.

PMID- 14674878
TI  - Frontolimbic response to negative feedback in clinical depression.
AB  - Functional neuroimaging suggests that limbic regions of the medial frontal cortex
      may be abnormally active in individuals with depression. These regions, including
      the anterior cingulate cortex, are engaged in both action regulation, such as
      monitoring errors and conflict, and affect regulation, such as responding to
      pain. The authors examined whether clinically depressed subjects would show
      abnormal sensitivity of frontolimbic networks as they evaluated negative
      feedback. Depressed subjects and matched control subjects performed a video game
      in the laboratory as a 256-channel EEG was recorded. Speed of performance on each
      trial was graded with a feedback signal of A, C, or F. By 350 ms after the
      feedback signal, depressed subjects showed a larger medial frontal negativity for
      all feedback compared with control subjects with a particularly striking response
      to the F grade. This response was strongest for moderately depressed subjects and
      was attenuated for subjects who were more severely depressed. Localization
      analyses suggested that negative feedback engaged sources in the anterior
      cingulate and insular cortices. These results suggest that moderate depression
      may sensitize limbic networks to respond strongly to aversive events.

PMID- 14674879
TI  - Neurophysiological evidence for disturbances of conflict processing in patients
      with schizophrenia.
AB  - Deficits in cognition are a hallmark of schizophrenia. In the present study, the
      authors investigated the effects of schizophrenia on the neural correlates of
      conflict processing in a single-trial version of the Stroop task by using event
      related brain potentials. Relative to matched controls, patients with
      schizophrenia showed increased Stroop interference in response time, but this
      effect was eliminated when the effect of response slowing was controlled. In
      controls, conflict processing was associated with a negative wave peaking between
      400 and 500 ms (N450) and conflict sustained potential (SP) peaking between 600
      and 800 ms after stimulus onset. In patients with schizophrenia, the amplitude of
      the N450 was significantly attenuated and the conflict SP was absent. These
      results provide evidence for the existence of altered neural processes associated
      with conflict processing that may be associated with dysfunction of the anterior
      cingulate and prefrontal cortex in patients with schizophrenia.

PMID- 14674880
TI  - Event-related FMRI study of context processing in dorsolateral prefrontal cortex
      of patients with schizophrenia.
AB  - Context processing is conceptualized as an executive function involved in
      voluntary, complex actions such as overcoming automatic responses. The present
      study tested the hypothesis that context-processing deficits in patients with
      schizophrenia are associated with a dysfunction of left dorsolateral prefrontal
      cortex (DLPFC). Using event-related functional magnetic resonance imaging (fMRI),
      17 controls and 17 medicated patients performed a version of the AX task in which
      a learned, automatic response had to be inhibited. In controls, left DLPFC
      activity increased when preparing to overcome an automatic response, whereas
      patients with schizophrenia showed no differential activation. In controls,
      context processing appeared to be associated with the differential representation
      of cues associated with the need to provide top-down support for overcoming
      automatic responses. This mechanism appeared to be impaired in patients with
      schizophrenia.

PMID- 14674881
TI  - Neutralizing increases discomfort associated with obsessional thoughts: an
      experimental study with obsessional patients.
AB  - Cognitive-behavioral theories suggest that the development of neutralizing is
      crucial in the development and persistence of obsessional problems (OCD). Twenty
      nine patients with a Diagnostic and Statistical Manual of Mental Disorders (4th
      ed., American Psychiatric Association, 1994) diagnosis of OCD were randomly
      allocated to 2 conditions. Both listened to repeated recorded presentations of
      their intrusive thoughts and either neutralized (experimental group) or
      distracted themselves (control). Discomfort was rated during this 1st phase and
      then during a 2nd phase without neutralizing or distraction. The experimental
      group showed a similar level of discomfort in the 1st phase, which significantly
      reduced during the period compared with controls. The experimental group
      experienced significantly more discomfort during the 2nd phase, and significantly
      stronger urges to neutralize and distract at the end of this phase than controls.

PMID- 14674882
TI  - Thrombospondin-4 A387P polymorphism is not associated with coronary artery
      disease and myocardial infarction in the Chinese Han population.
AB  - Recently, conflicting data have been reported regarding the possible contribution
      of the TSP-4 (thrombospondin-4) A387P polymorphism to CAD (coronary artery
      disease) or MI (myocardial infarction). To investigate a possible association
      between the A387P polymorphism and CAD or MI in the Chinese Han population, we
      conducted a case-controlled study including 817 patients with angiographically
      verified CAD or those who survived an acute MI and 847 control subjects. The TSP
      4 A387P polymorphism was determined by PCR and PCR-RFLP (restriction-fragment
      length polymorphism) analysis. The prevalence of the 387P allele was 3.8% in the
      healthy controls, which was less frequent than those in Western populations (19.6
      23.2%). No association of the A387P polymorphism with an altered risk of CAD, MI
      or premature MI was found in our present study (CG+CC compared with GG, P
      (CAD)=0.51, P (MI)=0.13, P (Premature MI)=0.17 respectively). We concluded that a
      relationship between the TSP-4 A387P polymorphism and CAD or MI was unlikely in
      our population. Additional investigations should be performed in populations at
      different risk of coronary events in order to elucidate further the possible
      contribution of this polymorphism to cardiovascular disease.

PMID- 14674883
TI  - Diversity of folds in animal toxins acting on ion channels.
AB  - Animal toxins acting on ion channels of excitable cells are principally highly
      potent short peptides that are present in limited amounts in the venoms of
      various unrelated species, such as scorpions, snakes, sea anemones, spiders,
      insects, marine cone snails and worms. These toxins have been used extensively as
      invaluable biochemical and pharmacological tools to characterize and discriminate
      between the various ion channel types that differ in ionic selectivity, structure
      and/or cell function. Alongside the huge molecular and functional diversity of
      ion channels, a no less impressive structural diversity of animal toxins has been
      indicated by the discovery of an increasing number of polypeptide folds that are
      able to target these ion channels. Indeed, it appears that these peptide toxins
      have evolved over time on the basis of clearly distinct architectural motifs, in
      order to adapt to different ion channel modulating strategies (pore blockers
      compared with gating modifiers). Herein, we provide an up-to-date overview of the
      various types of fold from animal toxins that act on ion channels selective for
      K+, Na+, Ca2+ or Cl- ions, with special emphasis on disulphide bridge frameworks
      and structural motifs associated with these peptide folds.

PMID- 14674885
TI  - Calcium-dependent regulation of tumour necrosis factor-alpha receptor signalling
      by copine.
AB  - The role of copines in regulating signalling from the TNF-alpha (tumour necrosis
      factor-alpha) receptor was probed by the expression of a copine dominant-negative
      construct in HEK293 (human embryonic kidney 293) cells. The construct was found
      to reduce activation of the transcription factor NF-kappaB (nuclear factor
      kappaB) by TNF-alpha. The introduction of calcium into HEK293 cells either
      through the activation of muscarinic cholinergic receptors or through the
      application of the ionophore A23187 was found to enhance TNF-alpha-dependent
      activation of NF-kappaB. This effect of calcium was completely blocked by the
      copine dominant-negative construct. TNF-alpha was found to greatly enhance the
      expression of endogenous copine I, and the responsiveness of the TNF-alpha
      signalling pathway to muscarinic stimulation increased in parallel with the
      increased copine I expression. The copine dominant-negative construct also
      inhibited the TNF-alpha-dependent degradation of IkappaB, a regulator of NF
      kappaB. All of the effects of the dominant-negative construct could be reversed
      by overexpression of full-length copine I, suggesting that the construct acts
      specifically through competitive inhibition of copine. One of the identified
      targets of copine I is the NEDD8-conjugating enzyme UBC12 (ubiquitin C12), that
      promotes the degradation of IkappaB through the ubiquitin ligase enzyme complex
      SCF(betaTrCP). Therefore the copine dominant-negative construct might inhibit TNF
      alpha signalling by dysregulation or mislocalization of UBC12. Based on these
      results, a hypothesis is presented for possible roles of copines in regulating
      other signalling pathways in animals, plants and protozoa.

PMID- 14674884
TI  - Identification of the human mitochondrial S-adenosylmethionine transporter:
      bacterial expression, reconstitution, functional characterization and tissue
      distribution.
AB  - The mitochondrial carriers are a family of transport proteins that, with a few
      exceptions, are found in the inner membranes of mitochondria. They shuttle
      metabolites and cofactors through this membrane, and connect cytoplasmic
      functions with others in the matrix. SAM (S-adenosylmethionine) has to be
      transported into the mitochondria where it is converted into S
      adenosylhomocysteine in methylation reactions of DNA, RNA and proteins. The
      transport of SAM has been investigated in rat liver mitochondria, but no protein
      has ever been associated with this activity. By using information derived from
      the phylogenetically distant yeast mitochondrial carrier for SAM and from related
      human expressed sequence tags, a human cDNA sequence was completed. This sequence
      was overexpressed in bacteria, and its product was purified, reconstituted into
      phospholipid vesicles and identified from its transport properties as the human
      mitochondrial SAM carrier (SAMC). Unlike the yeast orthologue, SAMC catalysed
      virtually only countertransport, exhibited a higher transport affinity for SAM
      and was strongly inhibited by tannic acid and Bromocresol Purple. SAMC was found
      to be expressed in all human tissues examined and was localized to the
      mitochondria. The physiological role of SAMC is probably to exchange cytosolic
      SAM for mitochondrial S-adenosylhomocysteine. This is the first report describing
      the identification and characterization of the human SAMC and its gene.

PMID- 14674886
TI  - NapGH components of the periplasmic nitrate reductase of Escherichia coli K-12:
      location, topology and physiological roles in quinol oxidation and redox
      balancing.
AB  - Nap (periplasmic nitrate reductase) operons of many bacteria include four common,
      essential components, napD, napA, napB and napC (or a homologue of napC ). In
      Escherichia coli there are three additional genes, napF, napG and napH, none of
      which are essential for Nap activity. We now show that deletion of either napG or
      napH almost abolished Nap-dependent nitrate reduction by strains defective in
      naphthoquinone synthesis. The residual rate of nitrate reduction (approx. 1% of
      that of napG+ H+ strains) is sufficient to replace fumarate reduction in a redox
      balancing role during growth by glucose fermentation. Western blotting combined
      with beta-galactosidase and alkaline phosphatase fusion experiments established
      that NapH is an integral membrane protein with four transmembrane helices. Both
      the N- and C-termini as well as the two non-haem iron-sulphur centres are located
      in the cytoplasm. An N-terminal twin arginine motif was shown to be essential for
      NapG function, consistent with the expectation that NapG is secreted into the
      periplasm by the twin arginine translocation pathway. A bacterial two-hybrid
      system was used to show that NapH interacts, presumably on the cytoplasmic side
      of, or within, the membrane, with NapC. As expected for a periplasmic protein, no
      NapG interactions with NapC or NapH were detected in the cytoplasm. An in vitro
      quinol dehydrogenase assay was developed to show that both NapG and NapH are
      essential for rapid electron transfer from menadiol to the terminal NapAB
      complex. These new in vivo and in vitro results establish that NapG and NapH form
      a quinol dehydrogenase that couples electron transfer from the high midpoint
      redox potential ubiquinone-ubiquinol couple via NapC and NapB to NapA.

PMID- 14674887
TI  - A novel missense mutation in the gene encoding SLURP-1 in patients with Mal de
      Meleda from northern Tunisia.
AB  - BACKGROUND: Mal de Meleda (MDM) is a rare autosomal recessive skin disorder which
      belongs to the clinically and genetically heterogeneous group of palmoplantar
      keratodermas (PPK). Clinically, MDM is characterized by erythema and
      hyperkeratosis of the palms and soles with sharp demarcation that appears soon
      after birth and progressively extends to the dorsal surface of the hands and
      feet. OBJECTIVES: Except for the molecular study reported in Algerian families,
      MDM has not yet been investigated in the Maghrebian population, characterized by
      its heterogeneous ethnic background and a high rate of consanguinity. In this
      study we report genetic and molecular investigations of eight unrelated
      consanguineous Tunisian families including 17 affected individuals. METHODS:
      Eight large consanguineous MDM families who originated from cities of northern
      Tunisia, with a total of 17 patients and 22 unaffected family members were
      investigated. Families were genotyped with the following microsatellite markers:
      CNG003, D8S1751 and D8S1836. Mutation analyses were performed in affected
      patients, in both parents and in unaffected individuals. Linkage analysis was
      also performed. RESULTS: All the clinical features of MDM were constantly
      present. Nevertheless variable severity was noted among patients. Histological
      details were recorded. The haplotype analysis of markers CNG003, D8S1751 and
      D8S1836 revealed that all affected offspring were homozygous by descent for the
      three polymorphic markers. The maximum lod score value, 3.22, confirmed the
      evidence for linkage to the ARS gene. Three haplotypes were observed, and the
      findings suggest that at least three different mutations within the ARS gene
      segregate with these haplotypes. Three different mutations were identified, the
      82delT mutation previously described and two novel missense mutations.
      CONCLUSIONS: The results suggest that the ARS gene is likely to be responsible
      for MDM in the eight Tunisian families. The clinical variability in the
      expression of PPK in MDM Tunisian patients might be accounted for by the
      intervention of modifier genes influencing the MDM phenotype.

PMID- 14674888
TI  - Arsenite and arsenate activate extracellular signal-regulated kinases 1/2 by an
      epidermal growth factor receptor-mediated pathway in normal human keratinocytes.
AB  - BACKGROUND: Inorganic arsenic is an environmental contaminant and is associated
      with the increased risk of human skin cancer. Arsenic has been reported to
      activate or inhibit a variety of cellular signalling pathways which has effects
      on cell growth, differentiation and apoptosis. However, the molecular mechanisms
      of these arsenic-induced biological effects are not completely understood.
      OBJECTIVES: To understand the molecular basis for the mode of action of
      arsenicals, we examined the effect of arsenite and arsenate on the activation of
      mitogen-activated protein kinases (MAPK) and the upstream signalling cascade in
      normal human epidermal keratinocytes (NHEK). METHODS: NHEK were exposed to
      arsenite or arsenate. Western blot analysis was performed to determine the
      activation of extracellular signal-regulated kinases (ERK) 1/2, c-jun N-terminal
      kinases (JNK), p38, and MAPK or ERK kinases (MEK) 1/2. Epidermal growth factor
      receptor (EGFR) tyrosine phosphorylation and recruitment of its adaptor proteins,
      Shc and Grb2, to EGFR were detected by immunoprecipitation and Western blot
      analysis. RESULTS: Both arsenicals activated ERK1/2, which are most highly
      activated in response to mitogenic stimulation, in addition to JNK and p38, which
      show greater activation in response to cellular stresses. The kinetics of ERK1/2
      activation differed from those of JNK and p38 activation. Both arsenicals
      transiently activated ERK1/2 prior to JNK and p38 activation. MEK1/2, upstream
      kinases of ERK1/2, were also activated by arsenicals with similar time kinetics
      to that of ERK1/2 activation. To investigate a signalling pathway leading to
      activation of MEK1/2-ERK1/2, we examined the tyrosine phosphorylation of EGFR and
      Shc adapter protein. Both arsenicals stimulated tyrosine phosphorylation of EGFR
      and Shc. After arsenical treatment, Shc immunoprecipitates contained
      coprecipitated EGFR and Grb2, suggesting that both arsenicals induce the assembly
      of EGFR-Shc-Grb2 complexes. Both the EGFR inhibitor tyrphostin AG1478 and anti
      EGFR blocking antibody markedly attenuated ERK1/2 activation induced by
      arsenicals, but did not affect JNK and p38 activation. CONCLUSIONS: Our data
      indicate that both arsenite and arsenate activate the EGFR-Shc-Grb2-MEK1/2-ERK1/2
      signalling cascade in NHEK.

PMID- 14674889
TI  - Interaction of cutaneous lymphoma cells with reactive T cells and dendritic
      cells: implications for dendritic cell-based immunotherapy.
AB  - BACKGROUND: Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of skin
      neoplasms that originate from T lymphocytes. An anti-CTCL T-cell immunity has
      been described but seems to be inefficient to clear CTCL cells. It is not known
      whether cutaneous dendritic cells (DCs) perpetuate the proliferation of the
      malignant CTCL cell clone or play a role in the control of this usually slowly
      progressing disease. OBJECTIVES: To characterize CTCL cell properties in the
      control of anti-CTCL T cells and to pave the way for a DC-based immunotherapy for
      CTCL. METHODS: We studied the interaction of a CTCL cell line with DCs and with
      allogeneic T cells. RESULTS: We found an antigen non-specific capacity of viable
      but not apoptotic CTCL cells to hamper CD4+ and CD8+ T-cell proliferation in a
      dose-dependent manner, indicating a suppressive potential of CTCL cells. Both
      viable and apoptotic CTCL cells were phagocytosed by immature DCs but only
      apoptotic CTCL cells induced an upregulation of DC maturation markers to a degree
      which enabled classification of these DCs as semimature. CTCL cells did not
      respond with proliferation when encountering allogeneic, mature DCs either loaded
      with CTCL cell material or unloaded, indicating a role for DCs in the induction
      of anti-CTCL T-cell immunity rather than in perturbation of clonal proliferation.
      For the loading of DCs with CTCL material lysate seems to be optimal as apoptotic
      cells were not phagocytosed extensively and necrotic CTCL material induced a
      partial cellular toxicity in DCs. DCs loaded with CTCL material were
      cryopreservable without significant loss of DC viability, surface marker
      expression or allostimulatory activity. CONCLUSIONS: Together, these data argue
      in favour for a DC-based immunotherapy for CTCL patients and provide an
      experimental protocol for preparing CTCL cell-loaded DCs.

PMID- 14674890
TI  - Paraneoplastic pemphigus in association with Castleman's disease.
AB  - BACKGROUND: Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease
      associated with lymphoproliferative neoplasms, and frequently with a very rare
      tumour, Castleman's disease. OBJECTIVES: To analyse the clinical history,
      immunopathological and histopathological findings in 28 patients with a confirmed
      diagnosis of PNP and Castleman's disease. METHODS: Sera from all patients were
      assayed by indirect immunofluorescence (IF) and immunoprecipitation (IP) for
      plakin autoantibodies, immunoblotting for detection of plectin autoantibodies,
      and enzyme-linked immunosorbent assay for detection of desmoglein (Dsg)1 and Dsg3
      autoantibodies. RESULTS: Severe oral mucositis was observed in all patients, and
      lichenoid cutaneous lesions were seen in 19 of 28. Twenty cases of Castleman's
      disease were of the hyaline vascular type, four were of plasmacytoid type and
      four were of mixed type. Striking findings included pulmonary destruction leading
      to bronchiolitis obliterans in 26 patients and fatal outcome due to respiratory
      failure in 22 patients with pulmonary involvement. Histological findings included
      lichenoid and interface dermatitis with variable intraepithelial acantholysis.
      Direct IF showed deposition of IgG and C3 in the mouth and skin in 24 of 28
      patients. However, indirect IF detected serum IgG autoantibodies in all patients.
      IP revealed IgG autoantibodies against desmoplakin I, envoplakin and periplakin
      in all cases, and against desmoplakin II and the 170-kDa antigen in 19 patients.
      Dsg3 and Dsg1 autoantibodies were present in 22 and 11 patients, respectively,
      and plectin autoantibodies in 23 patients. CONCLUSIONS: PNP in association with
      Castleman's disease presents with severe oral mucositis and cutaneous lichenoid
      lesions. Serum autoantibodies against plakin proteins are the most diagnostic
      markers. Pulmonary injury with respiratory failure is the cause of death in most
      cases.

PMID- 14674891
TI  - Prognostic factors in Sezary syndrome: a study of 28 patients.
AB  - BACKGROUND: The new European Organization for Research and Treatment of Cancer
      classification considers Sezary syndrome (SS) among the aggressive epidermotropic
      cutaneous T-cell lymphomas (ECTLs). Recent technological advances have
      facilitated the diagnosis of this disease, but it remains practically incurable,
      with a median survival of about 2.5-5 years. Deaths are due in part to the
      iatrogenic effects of treatments, which suggests that the management of SS could
      be improved. OBJECTIVES: Retrospectively to study the prognostic criteria related
      to disease progression. METHODS: Thirty patients with SS were followed up in the
      Dermatology Department of the University Hospital in Nantes, France, between
      January 1989 and May 2000. The diagnosis of SS was based on at least three of the
      following criteria: erythroderma, histological evidence of ECTL, a level of 20%
      or more circulating Sezary cells, and loss of My7 antigen expression by basal
      cells of the epidermis. Two patients not seen again after the initial diagnosis
      were excluded from the statistical study. RESULTS: The median disease-specific
      survival of the 28 patients was 64.55 +/- 10.11 months. The prognostic factors
      found in univariate analysis were age at diagnosis (P = 0.0109), interval before
      diagnosis (P = 0.0566), lactate dehydrogenase (LDH) level (P = 0.042) and
      presence of the Epstein-Barr virus (EBV) genome (BHLF in in situ hybridization)
      in skin (P = 0.0079). The prognostic factors found in multivariate analysis were
      age, interval before diagnosis and presence of the EBV genome in keratinocytes. A
      decreased number of Langerhans cells in the epidermis did not appear to be a
      prognostic factor. CONCLUSIONS: Our study confirms the prognostic value of age
      and LDH level, and for the first time demonstrates the prognostic value of the
      identification of the EBV genome in the skin. This seems consistent with a marked
      immune deficit during severe forms of SS.

PMID- 14674892
TI  - The dermoscopic classification of atypical melanocytic naevi (Clark naevi) is
      useful to discriminate benign from malignant melanocytic lesions.
AB  - BACKGROUND: The dermoscopic classification is a useful tool for handling patients
      with atypical naevi (Clark naevi). OBJECTIVES: To investigate if the dermoscopic
      classification of atypical naevi is of any value to discriminate benign from
      malignant melanocytic lesions. METHODS: Consecutive patients (n = 205) were
      included with 254 suspicious melanocytic lesions, confirmed by histopathology at
      the Pigmented Lesions Clinic of the Department of Dermatology, University Medical
      Center, University of Tuebingen, Germany. In this retrospective study,
      dermoscopic images of benign and malignant melanocytic lesions were classified
      according to the dermoscopic classification of atypical naevi (reticular,
      globular, homogeneous or combinations of two of these) and pigmentation (uniform,
      central hyper- or hypopigmentation, eccentric peripheral hyper- or
      hypopigmentation, or multifocal hyper- or hypopigmentation). The three-structure
      type (reticular, globular and homogeneous) was additionally defined. RESULTS:
      Reticular, homogeneous and reticular-homogeneous types were significantly more
      frequent in naevi than in melanomas, whereas the three-structure type was
      significantly more frequent in melanomas (P < 0.001). A sensitivity of 86.7%,
      specificity of 87.7% and diagnostic accuracy of 87.4% was obtained. Uniformly
      pigmented and centrally hyperpigmented types were significantly more frequent in
      naevi than in melanomas, whereas eccentric peripheral hyperpigmented and
      multifocal hyper- or hypopigmented types were significantly more frequent in
      melanomas (P < 0.001). CONCLUSIONS: The dermoscopic classification of atypical
      naevi (Clark naevi) is useful to discriminate benign from malignant melanocytic
      lesions. The three-structure type and eccentric peripheral hyperpigmentation were
      significantly more frequently found in malignant than in benign melanocytic
      lesions. The knowledge of these two dermoscopic types should be helpful for the
      management of patients presenting with multiple melanocytic lesions.

PMID- 14674893
TI  - Occupational skin disease in the construction industry.
AB  - BACKGROUND: Construction workers have a substantial risk of developing irritant
      and/or allergic contact dermatitis. Unfortunately, however, there is little
      population-based epidemiological data relating to occupational skin diseases
      (OSD) in the European construction industry that allow assessment of preventive
      measures. OBJECTIVES: In this investigation, the yearly incidence rates and
      causes of OSD in the construction industry were analysed on the basis of our
      register in Northern Bavaria. METHODS: From 1990 until 1999, all incidences of
      OSD in the construction industry were recorded prospectively. This enables the
      calculation of incidence rates of OSD in relation to the employed population in
      Northern Bavaria as recorded by the German Federal Employment Office. RESULTS: In
      the construction industry, a total of 335 OSD were registered. These comprise
      9.0% of all OSD in the register. We classified them into four relevant groups:
      (A) tile setters and terrazzo workers (incidence per 10 000 employees = 19.9);
      (B) painters (7.8); (C) construction and cement workers (5.2); and (D) wood
      processors (2.6). The overall incidence was 5.1 per 10 000 employees over 10
      years, which is a little below average for the entire register (6.7). Of these,
      43.6% were at least 40 years old. Allergic contact dermatitis (61.5%) occurred
      more often than irritant contact dermatitis (44.5%). Potassium dichromate caused
      roughly half of all cases of sensitization found to be occupationally relevant in
      the construction industry (152 cases) followed by epoxy resin (40) and cobalt
      chloride (32). CONCLUSIONS: The results indicate that potassium dichromate is
      still the most important allergen in the construction industry of Northern
      Bavaria; there has been no significant decline during the 1990s. This contrasts
      with the Scandinavian countries, where the prevalence of potassium dichromate
      sensitization declined following the reduction of chromium VI levels resulting
      from the addition of ferrous sulphate to cement. Within the construction
      industry, tile setters and terrazzo workers have a strikingly high incidence of
      OSD.

PMID- 14674894
TI  - Methylisothiazolinones elicit increased production of both T helper (Th)1- and
      Th2-like cytokines by peripheral blood mononuclear cells from contact allergic
      individuals.
AB  - BACKGROUND: Delayed-type hypersensitivity reactions to nickel (Ni2+) in humans
      are associated with increased production of both T helper (Th) 1- and Th2-like
      cytokines. Cytokine responses to the major group of contact allergens, i.e.
      organic compounds, have been less extensively studied. We have investigated here
      the cytokine production induced by a mixture of methylchloroisothiazolinone (MCI)
      and methylisothiazolinone (MI), the active ingredients in common preservatives
      that are capable of eliciting allergic contact dermatitis. OBJECTIVE: To
      characterize the immune response induced by MCI/MI in terms of the production of
      Th1- and Th2-like cytokines in peripheral blood mononuclear cells (PBMC) from
      allergic and non-allergic subjects. METHODS: Ten subjects with a history of
      contact allergy to MCI/MI and nine age-matched non-allergic volunteers
      participated. Their actual status was confirmed by patch testing. PBMC were
      cultured in the presence or absence of MCI/MI; cell proliferation was measured
      employing [3H]thymidine incorporation; and the number of cytokine-producing cells
      was determined using the enzyme-linked immunospot (ELISpot) assay and the levels
      of soluble cytokines in culture media by the enzyme-linked immunosorbent assay
      (ELISA). RESULTS: The proliferative response of PBMC to MCI/MI was significantly
      greater in the case of the allergic group than for the non-allergic group, as was
      the production of interleukin (IL)-2 and IL-13 (as determined by ELISpot and/or
      ELISA). PBMC from three of the allergic individuals with increased production of
      IL-2 and IL-13 responded to MCI/MI with elevated numbers of cells producing IL-4
      and IL-5. The increases in the production of IL-2, IL-4, IL-5 and IL-13 were
      positively correlated. CONCLUSION: MCI/MI elicited concomitant production of both
      Th1- and Th2-like cytokines by PBMC from subjects with contact allergy to these
      substances. This finding indicates that the organic compounds MCI/MI elicit a
      mixed Th1- and Th2-type of response, similar to that elicited by the metal ion
      Ni2+ in Ni2+-sensitized individuals.

PMID- 14674895
TI  - Bcl-2, Bcl-6 and CD10 expression in cutaneous B-cell lymphoma: further support
      for a follicle centre cell origin and differential diagnostic significance.
AB  - BACKGROUND: Primary cutaneous follicle centre cell lymphomas (PCFCCLs) are the
      most common type of cutaneous B-cell lymphoma. There is ongoing discussion on the
      origin of the neoplastic B cells in these PCFCCLs, and consequently on their
      relation to the groups of primary cutaneous marginal zone B-cell lymphomas
      (PCMZLs) and nodal follicular lymphomas. OBJECTIVES: To define better the
      neoplastic B cells in PCFCCLs, and to find out if differences in the expression
      of the antiapoptopic protein Bcl-2, and Bcl-6 and CD10, molecules which are
      normally expressed by the neoplastic B cells in nodal follicular lymphomas, might
      have diagnostic or prognostic significance in cutaneous B-cell
      lymphoproliferative disorders. METHODS: Pretreatment biopsies of well-defined
      groups of PCFCCL (n = 24), PCMZL (n = 14), primary cutaneous large B-cell
      lymphoma of the leg (PCLBCL-leg; n = 19), secondary cutaneous follicular lymphoma
      (n = 3) and cutaneous pseudo-B-cell lymphoma (n = 6) were investigated by
      immunohistochemistry for expression of Bcl-2, Bcl-6 and CD10. RESULTS: The
      PCFCCLs consistently expressed Bcl-6, whereas CD10 and Bcl-2 were expressed in
      only one and two of 24 cases, respectively. In contrast, PCMZLs were always
      negative for Bcl-6 and CD10, but were Bcl-2 positive, whereas skin and lymph node
      localizations of secondary cutaneous follicular lymphomas consistently expressed
      all of Bcl-2, Bcl-6 and CD10. Reactive follicle centre cells in pseudo-B-cell
      lymphomas expressed Bcl-6 (six of six cases) and CD10 (five of six cases), but
      not Bcl-2. PCLBCL-leg was Bcl-6 positive and CD10 negative in all cases,
      irrespective of clinical outcome, and strongly expressed Bcl-2 protein in all but
      two cases. CONCLUSIONS: The results of the present study provide further support
      for the follicle centre cell origin of both PCFCCL and PCLBCL-leg, and indicate
      that staining for Bcl-2, Bcl-6 and CD10 can serve as an important adjunct in the
      differential diagnosis of cutaneous B-cell lymphoproliferative disorders.

PMID- 14674896
TI  - Detection and typing of human papillomavirus in cutaneous warts of patients
      infected with human immunodeficiency virus type 1.
AB  - BACKGROUND: Cutaneous warts are caused by human papillomavirus (HPV). To date,
      more than 120 different types of HPV are known, of which 80 have been completely
      characterized. Prevalence studies on types of HPV present in cutaneous warts have
      been carried out in immunocompetent individuals and immunosuppressed organ
      allograft recipients, but not in human immunodeficiency virus (HIV)-positive
      patients. OBJECTIVES: To determine the HPV types present in cutaneous warts of
      HIV-infected patients. METHODS: Twenty-five biopsies of cutaneous warts from HIV
      infected patients and 14 samples from control non-HIV-infected patients were
      studied. HPV detection was performed by polymerase chain reaction using two sets
      of primers: MY09/MY11 and RK91. The type of HPV was determined by restriction
      fragment length polymorphism analysis and direct sequencing of the amplified
      products. RESULTS: HPV DNA was detected in 64% of cutaneous warts from HIV
      infected patients and in 79% of samples from the control group. The HPV types
      identified in HIV-infected patients were: HPV 2 (38%), 57 (31%), 27 (12%), 6
      (12%) and 7 (6%). HPV 2/27/57 predominated in both groups, being present in 81%
      of lesions from HIV-infected patients and 82% of samples from non-HIV-infected
      patients. HPV 6, a genital HPV type rarely found in cutaneous lesions, was
      detected in two warts from HIV-infected patients and in one lesion of the
      immunocompetent group. HPV 7, characteristically associated with butcher's warts,
      and recently detected in oral and perioral lesions of HIV-infected patients, was
      found for the first time in a non-facial lesion of an HIV-infected patient.
      CONCLUSIONS: This is the first study evaluating the prevalence of HPV types in
      cutaneous warts of HIV-infected patients and immunocompetent individuals in
      Brazil.

PMID- 14674897
TI  - Epidemiology of cutaneous melanoma and non-melanoma skin cancer in Schleswig
      Holstein, Germany: incidence, clinical subtypes, tumour stages and localization
      (epidemiology of skin cancer).
AB  - BACKGROUND: Population-based figures on skin cancer are essential for a realistic
      assessment of the personal disease burden, prevention modes and the need for
      caring. The Robert Koch Institute in Germany estimates the incidence of melanoma
      skin cancer as seven cases in 100 000 persons (age-standardized by the European
      standard rate). Population-based studies presumably show higher incidence rates
      of 10-16 cases in 100 000 persons. Few data exist for non-melanoma skin cancer
      (NMSC) as this is not systematically registered in Germany. OBJECTIVES: To
      present the first population-based results from the Schleswig-Holstein (Germany)
      Cancer Registry on incidence, stage distribution, clinical types and localization
      of skin cancer and to compare the results with other studies. METHODS: The Cancer
      Registry of the Bundesland Schleswig-Holstein with 3500 registering institutions,
      100 of which are dermatological institutions, investigates all notifiable
      incident cancer cases according to international standards. From the recorded
      data all melanoma and NMSC cases were identified and evaluated. RESULTS: Between
      1998 and 2001, 1784 malignant melanoma (MM) and 12 956 NMSC cases underwent
      diagnostic and analytical evaluation. For MM, age-standardized incidence rates
      were 12.3 and 14.8 in 100 000 men and women, respectively, and the mean age of
      men was greater than that of women (56.6 vs. 54.9 years, P < 0.05). Superficial
      spreading melanoma was the most frequent clinical type (39.1%). The tumours were
      predominantly located on the trunk in men (46.8%) in contrast to leg and hip in
      women (39.5%). For NMSC, the age-standardized incidence rates were 100.2 and 72.6
      in 100 000 men and women, respectively. More than 80% of all tumours were basal
      cell carcinoma. CONCLUSIONS: The first population-based data from Schleswig
      Holstein on the characteristics (age, sex, histological subtypes, localization
      and stage) of skin tumours agree well with the existing literature and may thus
      be regarded as representative. However, markedly higher incidences for MM and
      NMSC in the north of Germany compared with other parts of the country were
      observed. As the incidence rates from the north of Germany fit well into the
      European geographical pattern, we assume no regional increase. Therefore, the
      official German estimates on cutaneous tumours may largely depend on regional
      factors and may not be regarded as representative for all regions in Germany.

PMID- 14674898
TI  - Androgenetic alopecia in men aged 40-69 years: prevalence and risk factors.
AB  - BACKGROUND: The epidemiology of androgenetic alopecia (AGA) is not fully
      understood. Although a strong genetic basis has long been identified, little is
      known of its non-genetic causes. OBJECTIVES: To estimate the prevalence of and to
      determine risk factors for AGA in men aged 40-69 years in Australia. METHODS: Men
      (n = 1390) were recruited at random from the electoral rolls to serve as controls
      in a population-based case-control study of prostate cancer. All were interviewed
      in person and direct observations of AGA were made. Men were grouped into the
      following categories; no AGA, frontal AGA, vertex AGA and full AGA (frontal and
      vertex AGA). Epidemiological data collected from these men were used for an
      analysis of risk factors for each AGA category using unconditional logistic
      regression with AGA category as the response variable adjusting for age,
      education and country of birth. RESULTS: The prevalence of vertex and full AGA
      increased with age from 31% (age 40-55 years) to 53% (age 65-69 years).
      Conversely, the proportion of men with only frontal AGA was very similar across
      all age groups (31-33%). No associations were found between pubertal growth spurt
      or acne, reports of adult body size at time of interview, urinary symptom score,
      marital status, or current smoking status or duration of smoking and the risk of
      any form of AGA. The consumption of alcohol was associated with a significant
      increase in risk of frontal and vertex AGA but not full AGA. Men with vertex AGA
      had fewer female sexual partners but average ejaculatory frequency did not differ
      between men in different AGA categories. Reported weight and lean body mass at
      reaching maturity at about 21 years of age were negatively associated with vertex
      balding (P for trend < 0.05) but not with frontal AGA or full AGA. CONCLUSIONS:
      Evidence for environmental influences on AGA remains very slight. Our study
      failed to confirm previously reported or hypothesized associations with smoking
      and benign prostatic hypertrophy. The associations that we found with alcohol
      consumption and with lean body mass at age 21 years would be worthy of further
      research if they were able to be replicated in other studies.

PMID- 14674899
TI  - Risk factors influencing the development of hand eczema in a population-based
      twin sample.
AB  - BACKGROUND: A population-based twin study has recently shown that genetic factors
      are of significance for hand eczema. OBJECTIVES: To characterize further a sample
      of this twin material with regard to contact allergy, atopic dermatitis and wet
      work. METHODS: In total, 1076 individual twins were examined clinically and patch
      tested. The diagnosis of atopic dermatitis was based on the U.K. Working Party
      criteria. The decision concerning wet work was based on the individual job
      description, taking into account the later introduced definition of at least 2 h
      of water exposure daily. The data were analysed by a newly developed statistical
      method which makes it possible to analyse the individual risk factor and at the
      same time discriminate between genetic and environmental factors. RESULTS: The
      statistical analysis confirmed atopic dermatitis as an important risk factor for
      hand eczema. Contact allergy was also confirmed as a significant risk factor for
      hand eczema, and the risk was related to strength (+ to + + +) of contact
      allergy. The results indicated that the high frequency of hand eczema in women in
      comparison with men was caused by environmental and not genetic factors.
      Aggregation of hand eczema within twin pairs was only to a minor degree explained
      by atopic dermatitis and nickel allergy (or other contact allergies).
      CONCLUSIONS: We suggest that a hitherto unrecognized genetic risk factor for hand
      eczema independent of atopic dermatitis and contact allergy is probably of
      importance for the development of irritant contact dermatitis on the hands.

PMID- 14674900
TI  - A prospective study of the incidence of skin cancer and its risk factors in a
      Spanish Mediterranean population of kidney transplant recipients.
AB  - BACKGROUND: Skin cancer is the most common malignancy occurring in kidney
      transplant recipients (KTRs). OBJECTIVES: Our purpose was to investigate,
      prospectively, the cumulative incidence of cancerous and precancerous skin
      lesions as well as their risk factors in a close follow-up population of KTRs
      from a Mediterranean area of Spain. PATIENTS AND METHODS: One hundred and seventy
      four consecutive KTRs were examined at the moment of transplant and then at 6
      month intervals. The cumulative incidence of skin cancer was computed. To analyse
      the role of potential risk factors (age at transplantation, cause of renal
      failure, duration of pretransplant dialysis, type of immunosuppressive regimen,
      sun-reactive skin type and history of occupational sun exposure), the Cox
      regression method was used. RESULTS: After a median follow-up of 72 months
      (range, 12-140), 39 patients (25.3%) developed 142 tumours [84 basal cell
      carcinoma (BCC) and 58 squamous cell carcinoma (SCC)]. The BCC/SCC ratio was 1.4
      : 1. The cumulative incidence for skin cancer was 13% after 3 years of graft
      survival, increasing to 27.5% at 6 years and 48% at 10 years. Only age at the
      time of transplantation and occupational sun exposure had statistical
      significance as risk factors (P < 0.001). CONCLUSIONS: Our study confirms the
      high incidence of non-melanoma skin cancer among KTRs in a Mediterranean
      population with occupational sun exposure and the patient's age at the time of
      transplantation being the main risk factors. We believe that all organ transplant
      programs should provide educational information about protecting oneself from the
      sun as well as include follow-up visits by dermatologists in order to facilitate
      early diagnosis and treatment of skin cancer.

PMID- 14674901
TI  - A study of the correction factor for ultraviolet phototherapy dose measurements
      made by the indirect method.
AB  - BACKGROUND: Optimization of ultraviolet (UV) phototherapy for treatment of
      psoriasis and other skin conditions requires accurate dosimetry. One factor
      involved in whole body treatments is the correction that needs to be applied to
      radiometer measurements of irradiance made remotely without a person in the
      phototherapy cabin. OBJECTIVES: To evaluate the correction factor for cabins of
      different design and to consider whether different factors should be used for
      different phototherapy cabins and radiometers. METHODS: An automated UV dosimetry
      system capable of recording irradiances at positions around the circumference of
      a circle equating to a human trunk has been developed. The system has been
      combined with a phantom to derive values for the ratio between irradiance
      measurements made by the direct method with a person in a cabin, and indirect
      measurements recorded remotely. In addition, values for the ratio in UVA cabins
      have been derived from comparisons between measurements made directly by persons
      in a cabin and indirect measurements. RESULTS: Variations in direct to indirect
      ratio (DIR) with cabin type were less than between individual sets of
      measurements. The mean DIR obtained for cabins with TL01 lamps was 0.85 +/- 0.02,
      while that for UVA cabins was 0.80 +/- 0.05. The DIR for dual lamp (TL01/UVA)
      cabins, when TL01 lamps were illuminated, was higher (0.92). CONCLUSIONS: The DIR
      should be applied to any measurements made using radiometers without a person or
      equivalent phantom in a cabin. It is proposed that standard values are
      appropriate for groups of cabins with a single type of lamp and similar
      reflectors.

PMID- 14674902
TI  - A randomized controlled trial (volunteer study) of sitafloxacin, enoxacin,
      levofloxacin and sparfloxacin phototoxicity.
AB  - BACKGROUND: Fluoroquinolone antibiotics (FQs) are associated with phototoxic skin
      reactions following exposure to sunlight. OBJECTIVES: We aimed to compare the
      phototoxic potential of sitafloxacin, a novel FQ with three others: sparfloxacin,
      enoxacin, levofloxacin and placebo in Caucasian volunteers. In a second study,
      two dosage regimens of sitafloxacin were compared with placebo in Oriental
      subjects. METHODS: Randomized, placebo-controlled, assessor-blinded clinical
      trial. In 40 healthy Caucasians, sitafloxacin 100 mg twice a day (n = 8),
      sparfloxacin 200 mg day-1 (n = 8), enoxacin 200 mg three times a day (n = 8),
      levofloxacin 100 mg three times a day (n = 8) and placebo (n = 8) were given in
      oral doses for 6 days. In the second study, sitafloxacin 50 mg and 100 mg, both
      twice daily, were compared with placebo in 17 healthy Oriental subjects. Using an
      established monochromator technique, baseline threshold erythema levels were
      established pre-drug and on-drug. The phototoxic index (PI) baseline, minimal
      erythema dose (MED) divided by on-drug MED for each medication at each wavelength
      was determined and related to sitafloxacin peak plasma levels. The duration of
      susceptibility to phototoxicity was assessed by repeat phototesting daily after
      stopping medication. RESULTS: In the Caucasian study, sitafloxacin 100 mg twice a
      day produced mild ultraviolet (UV) A-dependent phototoxicity (median PI = 1.45)
      at 365 +/- 30 nm (half-maximum bandwidth), maximal at 24 h with normalization by
      24 h postdrug cessation. The sparfloxacin group experienced severe phototoxicity
      maximal at 24 h and, unusually for an FQ, extended in the visible region (430 +/-
      30 nm), maximal at 400 +/- 30 nm (median PI = 12.35) with abnormal pigmentation
      at on-drug phototest sites lasting, although fading, for up to 1 year. Enoxacin
      showed UVA-dependent phototoxicity (335-365 +/- 30 nm) median PI 3.94 (at 365 +/-
      30 nm) returning to normal 48 h after stopping the drug. Fading pigmentation at
      phototoxic sites also lasted up to 1 year. Phototoxicity was not detected in the
      levofloxacin or placebo groups. In the Oriental study, no clinically relevant
      phototoxicity was seen with either sitafloxacin or placebo groups. CONCLUSIONS:
      We conclude that 100 mg twice a day sitafloxacin in Caucasians is associated with
      a mild degree of cutaneous phototoxicity. Enoxacin 200 mg three times a day and
      sparfloxacin 200 mg day-1 are much more photoactive. Sparfloxacin phototoxicity
      is induced by UVA and visible wavelengths. Levofloxacin and placebo failed to
      show a phototoxic effect. In the Oriental study, sitafloxacin 50 mg twice a day
      and 100 mg twice a day failed to demonstrate a clinically significant phototoxic
      effect.

PMID- 14674903
TI  - Topical methyl aminolaevulinate photodynamic therapy in patients with basal cell
      carcinoma prone to complications and poor cosmetic outcome with conventional
      treatment.
AB  - BACKGROUND: Conventional treatment of basal cell carcinoma (BCC) causes morbidity
      and/or disfigurement in some patients because of the location (e.g. mid-face) and
      size of the lesion. OBJECTIVES: Following reports that such difficult-to-treat
      BCC lesions have been treated successfully with topical methyl aminolaevulinate
      (MAL) photodynamic therapy (PDT), a multicentre study was performed to determine
      the response of such BCC to MAL-PDT. METHODS: An open, uncontrolled, prospective,
      multicentre study was conducted comprising patients with superficial and/or
      nodular BCC who were at risk of complications, poor cosmetic outcome,
      disfigurement and/or recurrence using conventional therapy. Patients were given
      one or two cycles within 3 months of topical MAL-PDT, each consisting of two
      treatments 1 week apart. Tumour response was assessed clinically at 3 months
      after the last PDT, with histological confirmation of all lesions in clinical
      remission. The cosmetic outcome was rated. Patients with a BCC in remission will
      be followed up for 5 years for recurrence, of which the 24-month follow-up is
      reported here. Ninety-four patients with 123 lesions were enrolled and treated
      with MAL-PDT at nine European primary care and referral university hospitals. An
      independent blinded study review board (SRB) retrospectively excluded nine
      patients and a total of 15 lesions from the efficacy analysis, for not having a
      difficult-to-treat BCC according to the protocol. RESULTS: The lesion remission
      rate at 3 months was 92% (45 of 49) for superficial BCC, 87% (45 of 52) for
      nodular BCC, and 57% (four of seven) for mixed BCC, as assessed by clinical
      examination, and 85% (40 of 47), 75% (38 of 51), and 43% (three of seven),
      respectively, as assessed by histological examination and verified by the SRB. At
      24 months after treatment, the overall lesion recurrence rate was 18% (12 of 66).
      The cosmetic outcome was graded as excellent or good by the investigators in 76%
      of the cases after 3 months follow-up, rising to 85% at 12 months follow-up, and
      94% at 24 months follow-up. CONCLUSIONS: Topical MAL-PDT is effective in treating
      BCC at risk of complications and poor cosmetic outcome using conventional
      therapy. MAL-PDT preserves the skin and shows favourable cosmetic results.

PMID- 14674904
TI  - Ultraviolet B 308-nm excimer laser treatment of psoriasis: a new phototherapeutic
      approach.
AB  - BACKGROUND: Excimer laser-derived 308-nm ultraviolet (UV) B therapy is a new
      alternative for treating psoriasis by phototherapy. Some studies have been made
      showing the effectiveness of intralesional phototherapy technology in treating
      psoriasis. However, there has been no information available so far with regard to
      the cumulative dosage on a larger group of patients and on therapy optimized
      treatment strategies. OBJECTIVES: One hundred and twenty psoriatic patients were
      treated according to standard protocol to define the effectiveness. Our aim was
      to develop new parameters and determine whether effectiveness could be improved
      and whether treatment exposure, the cumulative UVB dose and adverse effects could
      be minimized. METHODS: Initially, the excimer laser's effectiveness in treating
      psoriasis was evaluated in an open prospective study according to standard
      protocol. This included 120 adult patients (67 female/53 male) with chronic
      plaque psoriasis and < 20% involved body surface. The initial dose was based on
      three multiples of a predetermined minimal erythema dose (MED). Patients were
      treated twice a week for the first 3 weeks, then once a week until clearance was
      achieved. The main parameters were the initial starting dose, psoriasis area and
      severity index (PASI), the number of treatments needed, the time in treatment and
      the cumulative dose needed to clear psoriatic plaques. Thereafter, 43 patients
      were treated as a second comparable group. Therapy began with a starter dose,
      defined as MED-I. MED-I was defined as a UVB 308-nm dose which provoked a visible
      increase in erythema after 24 h. In addition, the epidermal thickness of the
      plaques was measured on an individual basis by 20-MHz ultrasound and correlated
      to the MED-I. RESULTS: Of the patients who met the standard protocol, 65.7% were
      at least 90% clear after a maximum of 10 treatments; an even greater number
      (85.3%) showed a > or = 90% improvement in PASI after 13 sessions, while 14.7% of
      patients had only a < or = 50% PASI improvement. The cumulative UVB dose was
      11.25 +/- 4.21 J cm-2 and the average treatment time was 7.2 weeks. Patients
      treated individually with the MED-I starter dose showed nearly identical rates of
      clearance (83.7%), but were clear in 7.07 +/- 2.15 sessions with a cumulative
      dose of 6.25 +/- 4.02 J cm-2. CONCLUSIONS: The majority of our patients benefited
      greatly from laser-derived 308-nm UVB therapy, which cleared skin lesions faster
      than conventional phototherapy. As this therapy targets only the involved skin,
      the thickness of the plaques and individual MED-I should determine the initial
      dose, thus increasing the effectiveness of the therapy. We propose that light
      therapy sparing uninvolved skin will become predominant in the future.

PMID- 14674905
TI  - Optimizing the frequency of outpatient short-contact dithranol treatment used in
      combination with broadband ultraviolet B for psoriasis: a randomized, within
      patient controlled trial.
AB  - BACKGROUND: Recent concerns over the side-effects of psoralen plus ultraviolet
      (UV) A, immunosuppressive and cytotoxic treatments have led to increased interest
      in dithranol for treatment of psoriasis. Few studies have investigated how
      frequently dithranol should be applied. Dithranol-induced inflammation is maximal
      at 48-72 h, suggesting that daily application of dithranol may not be optimal.
      OBJECTIVES: To investigate the effectiveness of five times weekly application of
      short-contact dithranol (SCD) compared with three times weekly application in a
      dedicated hospital outpatient treatment unit. METHODS: A randomized, within
      patient, controlled study was performed. Patients had SCD applied five times
      weekly to one half of the body, and three times weekly to the other side. Whole
      body UVB irradiation was given 5 days a week. Patients were assessed weekly for 8
      weeks. Principal outcome measures were percentage reduction in modified Psoriasis
      Area and Severity Index (mPASI) at the end of study and time to 50% improvement
      in mPASI score. RESULTS: Twenty-nine patients were recruited; four were excluded
      from analysis. Mean percentage reduction in mPASI score at the end of study for
      five times weekly application was 57.3% (95% confidence interval, CI 39.6-75.0%)
      and for three times weekly application was 55.4% (95% CI 37.8-73.1%; P = 0.34).
      Mean time to 50% improvement in mPASI for five times weekly treatment was 4.1
      weeks and for three times weekly treatment was 4.0 weeks (P = 0.50). There was no
      difference in the frequency or severity of burning episodes for each side.
      CONCLUSIONS: This study suggests that three times weekly application of SCD may
      be as effective as five times weekly when used in conjunction with UVB
      administered five times weekly. Large studies of whole-body comparisons are
      warranted to assess further the optimal frequency of SCD and UVB therapy for
      psoriasis.

PMID- 14674906
TI  - Administration of oral activated charcoal in variegate porphyria results in a
      paradoxical clinical and biochemical deterioration.
AB  - BACKGROUND: Porphyrinogens are the obligate intracellular precursors of haem.
      These compounds are, however, unstable and are easily oxidized to the
      corresponding porphyrins, which are the form in which they are usually measured
      in the laboratory. A substantial enterohepatic cycling of porphyrins has been
      shown. Administration of oral activated charcoal, by interrupting this cycle, may
      reduce plasma and urine porphyrin levels in patients with some forms of
      porphyria. The effect of charcoal in subjects with variegate porphyria (VP) has
      not been reported. OBJECTIVES: To determine the clinical and biochemical effects
      of the administration of oral activated charcoal in patients with VP. METHODS:
      Oral activated charcoal was administered to eight subjects with VP. Clinical
      activity was assessed by skin lesion counts fortnightly for 6 weeks, 6 weeks
      after cessation of therapy, and during a subsequent 6-week control period during
      which no charcoal was taken. Urine and plasma porphyrins and urine precursors
      were measured by standard techniques. RESULTS: Treatment resulted in a
      significant increase in skin disease, urine and plasma porphyrins. CONCLUSIONS:
      Oral charcoal administration results in a paradoxical aggravation of VP,
      suggesting a complex and as yet undefined interaction of hepatic porphyrin
      metabolism and bowel porphyrin reabsorption. Oral sorbents should not be
      prescribed to subjects with VP.

PMID- 14674907
TI  - Prevalence of pityriasis versicolor in young Italian sailors.
AB  - BACKGROUND: Pityriasis versicolor is a superficial fungal disease with a world
      wide distribution, but there are few available studies on its prevalence in the
      general population. OBJECTIVES: To assess the prevalence of pityriasis versicolor
      in a representative sample of young Italian sailors, evaluating the influence of
      habits and risk factors in the affected individuals. METHODS: Young cadets (n =
      1024: 975 men and 49 women, mean age 22 years) of the Italian Navy Petty
      Officers' School in Taranto were consecutively examined by the same observer. The
      diagnosis of pityriasis versicolor was based on clinical picture and/or Wood's
      lamp examination. All the subjects filled in a questionnaire about sport
      practice, swimming pool attendance, marching, presence of hyperhidrosis and a
      positive clinical history of pityriasis versicolor in the past. The affected
      individuals were also asked if they were aware of their skin lesions. Differences
      between answers of affected and unaffected subjects were tested by Fisher's exact
      P-value test, and odds ratios were calculated. RESULTS: Pityriasis versicolor was
      diagnosed in 22 subjects (2.1%), all men, of whom 15 (68%) were not aware of
      their condition. No statistical association was found between active pityriasis
      versicolor and sport practice, swimming pool attendance, marching or presence of
      hyperhidrosis. A significant association [odds ratio 8.7 (95% confidence interval
      3.3-21.5); Fisher's exact P-value test P < 0.01] was documented between active
      pityriasis versicolor and a previous clinical history of pityriasis versicolor.
      CONCLUSIONS: The prevalence of pityriasis versicolor in this sample of young
      Italian sailors was not high, in agreement with the available surveys performed
      in the general population in temperate climates. Many affected subjects were not
      aware of their condition. The only important factor associated with pityriasis
      versicolor was a previous history of pityriasis versicolor. This observation
      could confirm the hypothesis that constitutional factors, e.g. seborrhoea and
      chemical constitution of sebum, may play a crucial role in temperate climates,
      leading to relapsing forms of this superficial mycosis.

PMID- 14674908
TI  - Granulocyte colony-stimulating factor-producing cutaneous angiosarcoma with
      leukaemoid reaction arising on a burn scar.
AB  - We report a 46-year-old man with a giant tumour in a burn scar on his buttock.
      Pathological examination revealed that the dermis was filled with anastomosing
      vascular channels and round- or spindle-type atypical cells, which were
      compatible with the diagnosis of cutaneous angiosarcoma. Based on prominent
      leucocytosis (up to 113 000 microL-1), we measured serum granulocyte colony
      stimulating factor (G-CSF). The highly elevated serum G-CSF of 303 ng L-1
      (normal, 6.1-21.5 ng L-1) and positive immunohistochemical staining of the tumour
      tissue for G-CSF indicated that G-CSF was produced by the cutaneous angiosarcoma.
      To our knowledge, this is the first reported case of G-CSF-producing cutaneous
      angiosarcoma.

PMID- 14674909
TI  - Scleromyxoedema: treatment of cutaneous and systemic manifestations with high
      dose intravenous immunoglobulin.
AB  - Scleromyxoedema is a rare disease characterized by cutaneous sclerosis, mucin
      deposition and paraproteinaemia. Internal disease is common, particularly
      musculoskeletal, gastrointestinal and central nervous system involvement. We
      report a series of three consecutive patients with scleromyxoedema treated with
      high-dose intravenous immunoglobulin (hdIVIg). Each of the three patients had
      relatively low levels of a highly basic IgG-lambda paraprotein, and each has
      demonstrated a sustained response of both their cutaneous and extracutaneous
      disease to hdIVIg. As all patients had perioral skin involvement and microstomia,
      one measure of cutaneous improvement was the increase in intraincisor distance.
      Extracutaneous manifestations of scleromyxoedema that improved included ureteral
      stricture, vocal strength and dysphagia.

PMID- 14674910
TI  - Henoch-Schonlein purpura in pregnancy.
AB  - Henoch-Schonlein purpura (HSP) is an IgA-mediated small vessel vasculitis which
      commonly involves the skin, gastrointestinal system and kidneys. Numerous HSP
      triggers have been identified, and pregnancy has been reported as an exacerbating
      factor. After a pregnant woman had been diagnosed as having new-onset HSP, we
      reviewed all cases of immunofluorescence-proven HSP evaluated by the Department
      of Dermatology at the Johns Hopkins Hospital between 1990 and 2002, and report
      three cases of HSP occurring during pregnancy. Two patients developed new-onset
      HSP, one at 16 weeks gestation and one at 22 weeks, while the third developed a
      recurrence of HSP at 12 weeks gestation after 19 years of remission. We conclude
      that pregnancy may be a trigger for HSP onset or recurrence in susceptible
      individuals.

PMID- 14674911
TI  - Nail dystrophy, an unusual presentation of incontinentia pigmenti.
AB  - We describe a 57-year-old woman with a history of nail dystrophy since the age of
      11 years. Multiple nail clippings were negative and multiple empirical treatments
      for presumed onychomycosis were unsuccessful. The patient has a daughter with
      classical incontinentia pigmenti. Molecular genetic analysis was positive for the
      NEMO gene deletion on the X chromosome, confirming the diagnosis of incontinentia
      pigmenti. Nail dystrophy was the sole feature of the disease in our patient.

PMID- 14674912
TI  - Bodybuilder oleoma.

PMID- 14674913
TI  - Erythema annulare centrifugum induced by generalized Phthirus pubis infestation.

PMID- 14674914
TI  - Pigmented squamous cell carcinoma of the skin. Report of a case with
      epiluminescence microscopic observation.

PMID- 14674915
TI  - Enhanced cytoplasmic expression of desmocollin 3 in epidermal rete ridges of
      Dowling-Degos syndrome.

PMID- 14674916
TI  - Bowel-associated dermatitis-arthritis syndrome associated with ileo-anal pouch
      anastomosis, and treatment with mycophenolate mofetil.

PMID- 14674917
TI  - Photodynamic therapy for bowenoid papulosis using a novel incoherent light
      emitting diode device.

PMID- 14674918
TI  - The relation between p53 expression and physical site of melanoma: an
      immunohistochemical study.

PMID- 14674919
TI  - Dermatitis herpetiformis Duhring with palmoplantar keratosis.

PMID- 14674920
TI  - Homozygous familial hypercholesterolaemia: development of xanthogranuloma in a
      boy at puberty under long-term low-density lipoprotein apheresis and drug
      therapy.

PMID- 14674921
TI  - Extensive fixed drug eruption due to the Japanese herbal drug "kakkon-to".

PMID- 14674922
TI  - A clinical dilemma while treating hypercholesterolaemia in psoriasis.

PMID- 14674923
TI  - Dramatic improvement of psoriasis with gemcitabine monotherapy.

PMID- 14674926
TI  - European Union meets the challenge of the growing importance of allergy and
      asthma in Europe.

PMID- 14674927
TI  - The role of antigen presenting cells at distinct anatomic sites: they accelerate
      and they slow down allergies.
AB  - It has been repeatedly demonstrated that allergic reactions are driven by the
      continuous flow of antigen uptake and presentation processes, which are
      perpetuated mainly by dendritic cells (DC). The ability of allergens to cause
      allergic inflammation is contingent upon the presence of an immunological milieu
      and microenvironment that either privileges Th2 responses or prohibits these
      reactions by the induction of contraregulatory anti-inflammatory activities of
      the immune system. In the light of recent developments it appears that DC have to
      manage two opposing tasks: on the one hand they can favor pro-inflammatory
      reactions and actively induce a T-cell response, yet on the other hand they serve
      an important function as 'silencers' in the immune system by sending out anti
      inflammatory, tolerance inducing signals. This unique capacity of DC has opened
      several exciting possibilities for a role of DC in both - accelerating and
      slowing down allergic reactions. It is therefore a challenge to understand in
      which way DC subtypes located at distinct anatomic sites with frequent allergen
      exposure, such as the skin, the nasal mucosa, the respiratory tree or the mucosa
      of the intestinal tract can have an impact on mechanisms involved in tolerance
      induction or effective immunity.

PMID- 14674928
TI  - The physiological and pathophysiological roles of eosinophils in the
      gastrointestinal tract.
AB  - Eosinophils and the gastrointestinal tract interact in an intimate and enigmatic
      relationship. Under healthy conditions, the presence of eosinophils is limited
      almost exclusively to the digestive tract mucosa where they exert several
      effector and immunoregulatory functions. While their precise function in the
      gastrointestinal tract is not completely understood, it is likely that, together
      with different T cell subsets, eosinophils are involved in maintaining the
      immunologic homeostastis across the mucosal barrier under resting conditions.
      Eosinophils also play a role in several inflammatory conditions, such as
      intestinal infections, hypersensitivity reactions, primary eosinophilic
      inflammations and several other chronic intestinal disorders. Depending on the
      responsible trigger, their effects may be beneficial or detrimental. Here, we
      discuss the available information regarding the physiological and pathological
      functions of eosinophils within the gastrointestinal tract.

PMID- 14674929
TI  - Monitoring the allergic inflammation.
AB  - Individual symptoms of allergy such as asthma, dermatitis, rhinitis have many
      different underlying mechanisms. The detailed characterization of the
      inflammatory mechanisms underlying symptom development in the individual patient
      is important in order to optimally control treatment. Measurement of eosinophil
      cationic protein (ECP) in sputum or blood and eosinophil protein X/eosinophil
      derived neurotoxin (EPX/EDN) in urine may be used to read the involvement of the
      eosinophil granulocyte in the process. An important information as eosinophil
      dominated processes seem to be particularly sensitive to corticosteroid
      treatment. The possibilities to measure the involvement of other inflammatory
      cells exist today, but are only used to a small extent. The dream would be that
      every patient with an inflammatory disease is characterized with respect to the
      profile of involving cells and mediators. Such information would provide us with
      a unique understanding of the underlying mechanisms of the development of disease
      symptoms and the possibilities of treating these.

PMID- 14674930
TI  - Diagnosis of asthma and permitted use of inhaled beta2-agonists in athletes.

PMID- 14674931
TI  - Sublingual or injection immunotherapy: the final answer?

PMID- 14674932
TI  - No effect of montelukast on asthma-like symptoms in elite ice hockey players.
AB  - BACKGROUND: Controlled clinical trials on the effects of leukotriene antagonists
      on asthma-like symptoms, bronchial hyperresponsiveness and airway inflammation
      have not been performed in elite athletes. METHODS: In 2001, we examined 88 of
      102 (86%) players from three junior, national league ice hockey teams in
      Helsinki. Athletes were included in the intervention if they reported at least
      two exercise-induced bronchial symptoms (wheeze, cough, shortness of breath)
      weekly during the previous month on a previously validated respiratory-symptom
      questionnaire. Sixteen male ice hockey players fulfilled the study criteria. A
      double-blind, randomized, cross-over, placebo-controlled study included 4-week
      active treatment (10 mg oral montelukast, bedtime), 1-week washout period, and 4
      week placebo treatment. Before entering the study, all patients were clinically
      examined, skin prick tested, filled in a respiratory symptom questionnaire,
      performed a spirometry and a histamine challenge test, and gave induced sputum
      samples. Exhaled NO was measured. These measures were repeated after both
      treatment periods. During the treatment the athletes kept daily diary on lower
      respiratory tract symptoms on a scale from 0 (no symptoms) to 10 (most severe
      symptoms), morning peak expiratory flow (PEF), training amount, and use of study
      medication. Primary end-point was daily lower respiratory tract symptom score.
      RESULTS: Montelukast had no effect on daily lower respiratory symptom scores,
      spirometry parameters [forced expiratory volume in 1 s (FEV1), forced vital
      capacity (FVC), FEV1/FVC ratio, PEF], bronchial hyperresponsiveness, sputum
      eosinophil or neutrophil cell counts, exhaled NO measurements, or morning PEF.
      Nine subjects were atopic in skin prick test, but their results did not differ
      from the nonatopic subjects. CONCLUSION: A leukotriene antagonist, montelukast,
      was of no benefit in the treatment of asthma-like symptoms, increased bronchial
      hyperresponsiveness or a mixed type of eosinophilic and neutrophilic airway
      inflammation in highly-trained ice hockey players.

PMID- 14674933
TI  - Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific
      immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy
      study.
AB  - BACKGROUND: Both sublingual allergen-specific immunotherapy (SLIT) and
      subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only
      few comparative studies have been performed. OBJECTIVE: To investigate the
      clinical efficacy of SLIT vs SCIT and secondary to compare SLIT and SCIT with
      placebo and to evaluate the relative clinical efficacy in relation to systemic
      side-effects. METHODS: A 3-year randomized, placebo-controlled, double-blind,
      double-dummy study including 71 adult birch pollen hay fever patients treated for
      two consecutive years after a baseline year. Allocation to treatment groups was
      based on disease severity in the baseline season, gender and age. RESULTS:
      Clinical efficacy was estimated in 58 patients completing the first treatment
      year by subtracting baseline data and by calculating the ratio first treatment
      season vs baseline. SLIT diminished the median disease severity to one-half and
      SCIT to one-third of placebo treatment. No statistical significant difference
      between the two groups was observed. Both for symptoms and medication scores
      actively treated patients showed statistically significant and clinical relevant
      efficacy compared with placebo. SLIT treatment only resulted in local mild side
      effects, while SCIT resulted in few serious systemic side-effects. CONCLUSION:
      Based on the limited number of patients the clinical efficacy of SLIT was not
      statistically different from SCIT, and both treatments are clinically effective
      compared with placebo in the treatment of birch pollen rhinoconjunctivitis. The
      lack of significant difference between the two treatments does not indicate
      equivalent efficacy, but to detect minor differences necessitates investigation
      of larger groups. Due to the advantageous safety profile SLIT may be favored.

PMID- 14674934
TI  - Matrix metalloproteinases MMP-7, MMP-9 and their tissue inhibitor TIMP-1:
      expression in chronic sinusitis vs nasal polyposis.
AB  - BACKGROUND: Nasal polyps (NP) are characterized by pseudocyst formation, whereas
      the mucosa in chronic sinusitis (CS) only shows a limited oedema. Matrix
      metalloproteinases (MMPs) are a family of endopeptidases able to degrade the
      extracellular matrix. Differences in histological features between CS and NP
      might be related to the respective expression of MMPs and their tissue inhibitors
      (TIMPs). OBJECTIVE: The aim of this study was to investigate MMP-7, MMP-9 and
      TIMP-1 proteins in NP and CS in comparison with normal mucosa. METHODS: Nasal
      samples, obtained from controls (n = 10), from NP (n = 8) and from CS (n = 10),
      were analysed by immunohistochemistry and enzyme-linked immunosorbent assay
      (ELISA). RESULTS: In NP, compared with controls, staining for MMP-9 and MMP-7
      appeared in blood vessels. Matrix metalloproteinase-9-positive inflammatory cells
      could be detected in increased numbers in pseudocyst formations. Concentrations
      of MMP-9 protein was found significantly increased in both CS and NP compared
      with controls, while MMP-7 was significantly increased in NP compared with
      controls and CS. Tissue inhibitors of metalloproteinase-1 protein was
      significantly increased in CS and NP when compared with controls. CONCLUSIONS:
      Chronic sinusitis and NP show different pattern of MMP-7/-9 and TIMP-1
      expression. We suggest that this difference in regulation of enzymes is related
      to the respective tissue remodelling observed in both diseases.

PMID- 14674935
TI  - Lack of association of HLA class I genes and TNF alpha-308 polymorphism in
      toluene diisocyanate-induced asthma.
AB  - BACKGROUND: Toluene diisocyanate (TDI)-induced asthma is a common cause of
      occupational asthma and it affects 5-15% of the exposed population suggesting an
      underlying genetic susceptibility. METHODS: To investigate the role of genetic
      factors in the development of TDI-induced asthma, we analyzed the distribution of
      human leukocyte antigen (HLA) class I genes and of tumor necrosis factor (TNF)
      alpha A-308G polymorphism in 142 patients with TDI-induced asthma and in 50
      asymptomatic exposed subjects. RESULTS: Neither the distribution of HLA class I
      antigens nor the distribution of TNF-alpha A-308G polymorphism was different
      between patients with TDI-induced asthma and asymptomatic exposed subjects.
      CONCLUSIONS: These results suggest that HLA class I antigens and TNF-alpha A-308G
      are not associated with susceptibility or resistance to the development of TDI
      induced asthma.

PMID- 14674936
TI  - Characterization of the protective and therapeutic efficiency of a DNA vaccine
      encoding the major birch pollen allergen Bet v 1a.
AB  - BACKGROUND: An estimated 100 million individuals suffer from birch pollen
      allergy. More than 95% of birch pollen-allergic subjects react with the major
      birch pollen allergen Bet v 1a, and almost 60% of them are sensitized exclusively
      to this allergen. OBJECTIVE: DNA immunization using the Bet v 1a gene was
      evaluated with respect to its prophylactic and therapeutic efficacy. METHODS: A
      DNA vaccine containing the entire Bet v 1a cDNA under the control of a CMV
      promoter was constructed. In order to estimate the protective efficiency, animals
      received three injections of this vaccine prior to sensitization with recombinant
      Bet v 1a. Vice versa, in a therapeutic approach, sensitization was followed by
      treatment with the DNA vaccine. RESULTS: The Bet v 1a DNA vaccine induced strong
      Bet v 1-specific antibody responses with a Th1-biased response type. Animals
      which received the DNA vaccine were protected against a following allergic
      sensitization with Bet v 1a. The protective effect was characterized by
      suppression of Bet v 1-specific immunoglobulin (Ig)E production, lack of basophil
      activation and enhanced interferon (IFN)-gamma expression. In a therapeutic
      situation, treatment of sensitized animals with DNA vaccines decreased IgE
      production, IgE-mediated basophil release and drastically reduced anaphylactic
      activity as measured by passive cutaneous anaphylaxis assays. Concerning the
      cellular immune response, DNA immunization induced a sustaining and dominant
      shift from a Th2 type response towards a balanced Th1/Th2 type response as
      indicated by increased IFN-gamma but unchanged IL-5 levels in lymphoproliferation
      assays. CONCLUSION: The results demonstrate the allergen-specific protective and
      therapeutic efficacy of a DNA vaccine encoding the clinically highly relevant
      allergen Bet v 1a indicating the suitability of this concept for the treatment of
      allergic diseases.

PMID- 14674937
TI  - Allergen specific immunotherapy attenuates early and late phase reactions in
      lower airways of birch pollen asthmatic patients: a double blind placebo
      controlled study.
AB  - BACKGROUND: Few placebo-controlled studies have examined the effect of allergen
      specific immunotherapy (SIT) on early and late phase asthmatic reactions. In this
      placebo-controlled study we have investigated the effect of 1 year of SIT with
      standardized birch pollen extract on early and late phase asthmatic reactions in
      adult asthmatic patients. METHODS: Nineteen patients with a history of birch
      pollen-induced seasonal symptoms from upper and lower airways, positive skin
      prick test and in vitro specific immunoglobulin E to birch pollen extract were
      included. Allergen and methacholine bronchial challenges were performed and blood
      samples obtained for analyses of total eosinophil count and eosinophil cationic
      protein (ECP) in serum, before and after 1 year of immunotherapy treatment.
      RESULTS: All patients developed early and 16 of 19 both early and late phase
      asthmatic reactions. A significant increase in allergen dose was required to
      evoke early asthmatic reaction in the immunotherapy group (P < 0.01) after 1 year
      of treatment. The difference between the groups was significant (P < 0.01). Also
      the size of late asthmatic reaction was significantly reduced in the SIT group
      compared with placebo treated patients (P < 0.01). Twenty-four hours after
      allergen challenge methacholine sensitivity, number of total eosinophils and ECP
      increased significantly in the placebo (P < 0.02, P < 0.05 and P < 0.05
      respectively), but not in the SIT group. CONCLUSION: Allergen SIT with
      standardized birch pollen extract decreased early and late asthmatic responses
      following bronchial challenge in pollen allergic patients, thus confirming anti
      inflammatory effect of the treatment.

PMID- 14674938
TI  - Increased sensitivity to IL-4 in cystic fibrosis patients with allergic
      bronchopulmonary aspergillosis.
AB  - BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is characterized by a
      heightened Th2 CD4+ T-cell response to Aspergillus fumigatus allergens and a
      hyper-immunoglobulin (Ig)E state compared with cystic fibrosis patients without
      ABPA. We hypothesize that one reason for this response is increased sensitivity
      to interleukin (IL)-4 in ABPA resulting in increased expression of CD23 and CD86
      and leading to a positive amplification mechanism that increases Th2 CD4+ T cell
      responses. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from
      seven ABPA CF and 19 non-ABPA CF patients and 16 nonatopic controls and
      stimulated with rIL-4 (range 0.1-10 ng/ml) and rIL-13 (range 1-10 ng/ml) for 48
      h. The number of CD23 molecules and percentages of CD23+ B cells were quantified
      by flow cytometry. Both phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO) and
      antigen stimulated, toxoid and Asp f2/f3/f4, PBMC were examined for cytoplasmic
      cytokine synthesis enumerated by cytokine staining using flow cytometry to
      measure Th2 and Th1 CD3+ T cells. RESULTS: The numbers of CD23 molecules on B
      cells were significantly elevated at time 0 in ABPA CF patients compared with
      both non-ABPA CF patients and nonatopic controls. Following IL-4 stimulation in
      vitro, the numbers and percentages of CD23 expression on B cells were
      significantly up-regulated in ABPA CF patients compared with non-ABPA CF patients
      and controls. The IL-13 stimulation up-regulated CD23 expression; however, there
      was no significant difference in ABPA CF patients compared with non-ABPA CF
      patients and controls. The percentages of interferon (IFN)-gamma+ CD3+T cells
      following PMA/IO stimulation were significantly decreased in both ABPA and non
      ABPA CF patients compared with controls. There were no significant differences of
      IL-4+ and IL-13+ CD3+ T cells between ABPA and non-ABPA CF patients. When tetanus
      toxoid stimulated T cells were examined, both ABPA and non-ABPA CF patients had
      significantly decreased IFN-gamma+ CD3+ T cells compared with controls. In Asp
      f2/f3/f4 stimulated T cells, ABPA CF patients had significantly increased IL-4+
      CD3+ T cells compared with non-ABPA CF patients and controls. CONCLUSIONS: ABPA
      CF patients have increased sensitivity to IL-4 but not to IL-13 up-regulation of
      CD23 molecules compared with non-ABPA CF patients. There were decreased
      percentages of IFN-gamma+ and IL-2+ Th1 T cells in CF patients compared with
      nonatopic controls but similar percentages of IL-4+ Th2 T cells in all three
      groups. However, ABPA CF patients had increased frequency of Aspergillus
      stimulated Th2 T cells. This indicated that there is skewing of Th2 T cells in
      ABPA CF patients. Thus, in CF ABPA patients there is increased Th2 T cells and
      increased sensitivity to IL-4.

PMID- 14674939
TI  - Fine-scale mapping of type I allergy candidate loci suggests central
      susceptibility genes on chromosomes 3q, 4q and Xp.
AB  - BACKGROUND: Type I allergy globally affects an increasing number of individuals
      with the consequence of considerable personal morbidity and socio-economic costs.
      Identification of disease susceptibility genes would render enormous medical
      perspectives in terms of improved diagnosis, treatment and prevention. Like for
      other complex disorders, achievement of the knowledge necessary depends on
      confirmation of reported genomic candidate regions. METHODS: We performed a two
      stage fine-scale linkage analysis in 11 selected candidate regions on chromosome
      3p, 3q, 4p, 4q, 5q, 6p, 9p, 12q, 12qter, 18q and Xp. We analysed 97 polymorphic
      markers in 424 individuals from 100 sib-pair families and evaluated the data for
      five phenotypes: Allergic asthma, atopic dermatitis, allergic rhinitis and total
      and specific immunoglobulin E. RESULTS: The highest maximum likelihood scores
      (MLS) were obtained on chromosomes 3q (MLS = 2.69), 4p (MLS = 2.34), 4q (MLS =
      2.75), 6p (MLS = 2.22), 12qter (MLS = 2.15) and Xp (MLS = 2.23). All five
      phenotypes showed MLS >/= 2 in one or more of the candidate regions. CONCLUSIONS:
      Susceptibility genes in the 3q, 4q and Xp regions may play a central role in the
      inheritance of allergic disease, as positive results were obtained for all five
      phenotypes in these three regions.

PMID- 14674940
TI  - Comparison of wheat and rye flour skin prick test solutions for diagnosis of
      baker's asthma.
AB  - BACKGROUND: Skin prick tests (SPTs) play an important role in the diagnosis of
      baker's asthma and in the investigation of sensitization frequencies in field
      studies. It was the aim of our study to compare different SPT solutions for wheat
      and rye flour sensitization and to assess the validity of test results. METHODS:
      Skin prick tests with wheat and rye flour were performed in parallel with
      extracts from different companies and compared with the results of bronchial
      challenge tests with both flours (69 rye flour and 51 wheat flour challenge
      tests). Additionally, specific immunoglobulin E (sIgE) to wheat and rye flour
      were tested. SPT solutions were analysed for protein content and by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: Skin
      prick test solutions for diagnosis of wheat and rye flour sensitization from
      three companies differed in protein concentrations and composition with the
      consequence of widely differing SPT results. Sensitivity of SPTs in comparison
      with allergen-specific bronchial challenge as a gold standard was between 40 and
      67%, specificity was between 86 and 100%, the positive predictive value (PPV)
      ranged from 81 to 100% and the negative predictive value (NPV) from 44 to 70%.
      These numbers were only marginally affected by using a combination of challenge
      test result and sIgE value as a more specific gold standard. CONCLUSION:
      Improvement and standardization of SPT extracts for wheat and rye flour is highly
      recommended.

PMID- 14674941
TI  - Infectious and uterus related complications during pregnancy and development of
      atopic and nonatopic asthma in children.
AB  - BACKGROUND: It has been suggested that environmental factors early in life,
      particularly related to hygiene and infections, seem to be involved in the
      increase of asthma and allergic disease observed recently in developed countries.
      The possible effect of these factors also in utero have yet to be completely
      clarified. The aim of this study was to investigate the association between
      infective and uterus related complications during pregnancy, as well as related
      drug factors, with atopic and nonatopic asthma in children. METHODS: This was a
      case-controlled study enrolling 338 children with asthma and 467 controls, who
      had never suffered from wheeze or asthma. Fever episodes, flu episodes,
      threatened abortions and related drug factors were retrospectively assessed by
      parental report via a standardized questionnaire. Atopy was determined by skin
      prick tests to 10 prevalent allergens at the time of examination. RESULTS: Flu
      episodes during pregnancy were significantly associated with development of
      asthma in children [adjusted odds ratio (aOR) 1.91; 95% confidence interval (95%
      CI) 1.1-3.2], mainly with nonatopic asthma. Fever episodes showed similar results
      (aOR 2.16; 95% CI 1.2-3.9), but were associated with both atopic and nonatopic
      asthma. The effect seems mainly due to flu and fever episodes contracted in the
      third trimester. Exposure to isoxsuprine was significantly associated with asthma
      (aOR 1.54; 95% CI 1.08-2.19) while threatened abortions were more frequent in the
      asthma group than in controls, although the difference was statistically
      significant only when such events occurred in the second trimester (aOR 2.06; 95%
      CI 1.07-3.94). Both threatened abortions and exposure to isoxsuprine were
      associated only with nonatopic asthma. CONCLUSIONS: This study confirms that
      prenatal infective complications may contribute to the development of asthma in
      children and show a possible role for a new risk factor for asthma, that is
      exposure to isoxsuprine. Therefore, larger prospective studies, capable of
      separating atopic and nonatopic asthma, would serve to confirm these results and
      to explain the possible mechanism through which these factors may act.

PMID- 14674942
TI  - Occupational exposure of Brazilian neonatal intensive care workers to latex
      antigens.
AB  - BACKGROUND: Frequent exposure to latex causes various reactions such as
      respiratory symptoms and anaphylactic shock. In these cases, proteins found in
      natural latex are responsible for the serious systemic antilatex-mediated
      immediate hypersensitive reactions. METHODS: Cross-sectional descriptive survey
      focusing on 96 Brazilian health care workers (HCW) in the neonatal intensive care
      unit at CAISM, State University of Campinas UNICAMP, Brazil. All subjects were
      interviewed, donated blood samples for the latex-specific immunoglobulin E
      measurement and underwent the skin prick test (SPT) with an antigen extracted
      from latex gloves. RESULTS: The prevalence of latex positive SPT was 8%. There
      were eight SPT positive and only one serologic test was in agreement with the
      SPT. Overall, there was evidence of an association between the latex SPT and
      reported eczema (P = 0.01); food allergy (P = 0.009) with pineapple (P = 0.01).
      CONCLUSIONS: These results suggest that the identification of reactions of
      immediate hypersensitivity mediated by antilatex antibodies in HCW should be
      encouraged to prevent occupational exposure to latex products.

PMID- 14674943
TI  - Disagreement and concerns regarding the article recently published by Macy and
      Burchette in Allergy 2002;57:1151.

PMID- 14674944
TI  - Reactions to several antibiotics several years after cutaneous tests for
      penicillin derivatives.

PMID- 14674946
TI  - Occupational asthma caused by carnation (Dianthus caryophyllus) with simultaneous
      IgE-mediated sensitization to Tetranychus urticae.

PMID- 14674947
TI  - Persistent asthma following accidental exposure to formaldehyde.

PMID- 14674948
TI  - Glottis oedema due to loratadine.

PMID- 14674949
TI  - Fixed drug eruption caused by articain.

PMID- 14674950
TI  - Stevens-Johnson syndrome associated with azithromycin followed by transient
      reactivation of herpes simplex virus infection.

PMID- 14674951
TI  - Delayed-type hypersensitivity to heparins.

PMID- 14674953
TI  - Psychiatric epidemiology of old age: the H70 study--the NAPE lecture 2003.
AB  - OBJECTIVE: To describe methodological issues and possibilities in the
      epidemiology of old age psychiatry using data from the H70 study in Goteborg,
      Sweden. METHOD: A representative sample born during 1901-02 was examined at 70,
      75, 79, 81, 83, 85, 87, 90, 92, 95, 97, 99 and 100 years of age, another during
      1906-07 was examined at 70 and 79 years of age, and samples born between 1922 and
      1930 were examined at 70 years of age. The study includes psychiatric
      examinations and key informant interviews performed by psychiatrists, physical
      examinations performed by geriatricians, psychometric testings, blood sampling,
      computerized tomographies of the brain, cerebrospinal fluid analyses,
      anthropometric measurements, and psychosocial background factors. RESULTS: Mental
      disorders are found in approximately 30% of the elderly, but is seldom detected
      or properly treated. Incidence of depression and dementia increases with age. The
      relationship between blood pressure and Alzheimer's disease is an example of how
      cross-sectional and longitudinal studies yield completely different results.
      Brain imaging is an important tool in epidemiologic studies of the elderly to
      detect silent cerebrovascular disease and other structural brain changes. The
      high prevalence of psychotic symptoms is an example of the importance to use
      several sources of information to detect these symptoms. Dementia should be
      diagnosed in all types of studies in the elderly, as it influences several
      outcomes such as mortality, blood pressure, and rates of depression. Suicidal
      feelings are rare in the elderly and are strongly related to mental disorders.
      CONCLUSION: Modern epidemiologic studies in population samples should be
      longitudinal and include assessments of psychosocial risk factors as well as
      comprehensive sets of biologic markers, such as brain imaging, neurochemical
      analyses, and genetic information to maximize the contribution that epidemiology
      can provide to increase our knowledge about the etiology of mental disorders.

PMID- 14674954
TI  - Lycanthropy--psychopathological and psychodynamical aspects.
AB  - OBJECTIVE: The imagination of being transformed into an animal or being an animal
      is called lycanthropy. The phenomenon is presented and psychodynamical aspects
      are discussed. METHOD: A literature review forms the base of this discussion of a
      psychopathological phenomenon. RESULTS: The lycanthropic symptomatology
      represents a spectrum of continuity of developmental and culture-dependent normal
      behaviour via partial forms to the complete picture of lycanthropy. It is
      observed in different mental disorders. CONCLUSION: Lycanthropy is interpreted by
      the authors as a delusion in the sense of the self-identity disorder defined by
      Scharfetter. It is mainly found in affective and schizophrenic disorders but can
      be a symptom of other psychiatric disorders as well. Psychodynamically this kind
      of delusion can be interpreted as an attempt to project suppressed affects,
      especially with aggressive or sexual content, into the figure of an animal.
      Psychotherapy and/or neuroleptic medication can be effective.

PMID- 14674955
TI  - Psychiatric comorbidity in first episode psychosis: the Early Psychosis
      Intervention Program (EPIP) experience.
AB  - OBJECTIVE: To determine the prevalence rates of psychiatric comorbidity in a
      hospitalized Asian patient group with first episode psychosis and examine its
      clinical correlates. METHOD: Seventy-nine consecutively admitted patients with
      first episode psychosis were assessed using the Structured Clinical Interview for
      DSM-IV-axis I disorders (patient edition), Positive and Negative Symptom Scale
      (PANSS), Scale to assess Unawareness of Mental Disorders (SUMD) and Global
      Assessment of Functioning (GAF) scales. RESULTS: Psychiatric comorbidity was
      present in 36.7% (n = 29) of the patients. Patients with psychiatric comorbidity
      were younger (P < 0.05), had an earlier onset of illness (P < 0.05) and better
      insight on social consequences and flat affect items (P < 0.05) on the SUMD. No
      significant differences were found between the two groups with and without
      psychiatric comorbidity in gender, ethnicity, marital status, length of
      education, employment status, living arrangements, duration of hospitalization
      and untreated psychosis as well as total PANSS and GAF scores. CONCLUSION:
      Psychiatric comorbidity is common thus calling for a greater awareness in
      clinicians of these conditions, which are often under-recognized, under-diagnosed
      and untreated.

PMID- 14674956
TI  - Fifteen-year follow-up of ICD-10 schizoaffective disorders compared with
      schizophrenia and affective disorders.
AB  - OBJECTIVE: The nosological status of schizoaffective disorders is still unclear.
      The aim of the present study was to compare ICD-10 schizoaffective disorders to
      schizophrenia and affective disorders with respect to the clinical picture and
      the long-term outcome. METHOD: Two hundred and forty-one first-admitted
      inpatients from the years 1980-1982 who fulfilled the ICD-10 criteria for
      schizophrenia, schizoaffective or affective disorders were included. Patients
      were examined at the time of first hospitalization and then followed-up after 15
      years. RESULTS: With respect to the clinical picture at the time of first
      hospitalization ICD-10 schizoaffective disorders were distinguishable from both
      schizophrenia and affective disorders. However, with respect to the long-term
      outcome ICD-10 schizoaffective disorders had a prognosis similar to that of
      affective disorders. CONCLUSION: Differing prognosis implies that schizoaffective
      disorders should be distinguished from schizophrenia and suggests their
      subcategorization under affective disorders.

PMID- 14674957
TI  - Childhood abuse as a risk factor for psychotic experiences.
AB  - OBJECTIVE: To examine the hypothesis that individuals from the general population
      who report childhood abuse are at increased risk of developing positive psychotic
      symptoms. METHOD: Data were derived from a general population sample of 4045
      subjects aged 18-64 years. First ever onset of positive psychotic symptoms at 2
      year follow-up were assessed using the Composite International Diagnostic
      Interview and additional clinical interviews if necessary. Childhood abuse was
      assessed at baseline. RESULTS: Baseline reported childhood abuse predicted
      development of positive psychotic symptoms associated with need for care [odds
      ratio (OR) = 11.5, 95% CI 2.6-51.6]. This association remained after adjustment
      for demographic variables, reported risk factors and presence of any lifetime
      psychiatric diagnosis at baseline (OR = 7.3, 95% CI 1.1-49.0). CONCLUSION: The
      results suggest that early childhood trauma increases the risk for positive
      psychotic symptoms. This finding fits well with recent models that suggest that
      early adversities may lead to psychological and biological changes that increase
      psychosis vulnerability.

PMID- 14674958
TI  - Determinants of quality of life in first-episode psychosis.
AB  - OBJECTIVE: To assess patient and/or illness characteristics associated with
      aspects of quality of life (QOL) in first-episode psychosis (FEP). METHOD:
      Patient characteristics, symptom ratings and Wisconsin QOL scale (client version)
      were assessed. Data were analysed with correlation coefficients and a
      hierarchical regression analysis. RESULTS: Patients presented with varying levels
      of QOL on different domains. The level of 'general satisfaction' was related to
      age of onset and social premorbid adjustment; 'weighted index of QOL' to social
      premorbid adjustment and inversely to educational premorbid adjustment; 'social
      relations' inversely to duration of untreated psychosis (DUP), length of prodrome
      and negative symptoms; 'psychological well-being' inversely to depression and
      educational premorbid adjustment; 'activities of daily living' to social
      premorbid adjustment and inversely to negative symptoms; and 'outlook on
      symptoms' to level of depression. CONCLUSION: Domains of self-rated QOL in FEP
      patients are differentially associated with malleable and non-malleable aspects
      of patient and illness characteristics.

PMID- 14674959
TI  - Rapid onset of comorbidity of common mental disorders: findings from the
      Netherlands Mental Health Survey and Incidence Study (NEMESIS).
AB  - OBJECTIVE: In a cohort of subjects with no history of psychopathology, we
      determined a 3-year incidence and the risk factors of comorbid and pure mood,
      anxiety and substance use disorders. METHOD: Data were obtained from the
      Netherlands Mental Health Survey and Incidence Study (NEMESIS), a longitudinal
      community study in which 4796 adults were interviewed in 1996, 1997 and 1999 with
      the Composite International Diagnostic Interview. RESULTS: Of 2869 cases at risk,
      10.8% developed an incident disorder within 3 years, of which 16.1% was comorbid.
      Neuroticism, childhood trauma and parental psychiatric history were more strongly
      associated with comorbid than with pure disorders. No differences emerged in
      events occurring in the first year after baseline, but events in the period
      thereafter showed markedly stronger associations with comorbidity and pure mood
      disorder than with pure anxiety and substance use disorder. Functional disability
      was also linked more strongly to comorbidity and pure mood disorder. CONCLUSION:
      Clear risk factors exist for the rapid onset of comorbidity. Interventions are
      needed to prevent rapid comorbidity in subjects who recently developed a primary
      disorder.

PMID- 14674960
TI  - Factor structure of DSM-IV criteria for obsessive compulsive personality disorder
      in patients with binge eating disorder.
AB  - OBJECTIVE: To examine the factor structure of DSM-IV criteria for obsessive
      compulsive personality disorder (OCPD) in patients with binge eating disorder
      (BED). METHOD: Two hundred and eleven consecutive out-patients with axis I
      diagnoses of BED were reliably assessed with semi-structured diagnostic
      interviews. The eight criteria for the OCPD diagnosis were examined with
      reliability and correlational analyses. Exploratory factor analysis was performed
      to identify potential components. RESULTS: Cronbach's coefficient alpha for the
      OCPD criteria was 0.77. Principal components factor analysis with varimax
      rotation revealed a three-factor solution (rigidity, perfectionism, and
      miserliness), which accounted for 65% of variance. CONCLUSION: The DSM-IV
      criteria for OCPD showed good internal consistency. Exploratory factor analysis,
      however, revealed three components that may reflect distinct interpersonal,
      intrapersonal (cognitive), and behavioral features.

PMID- 14674961
TI  - A controlled randomized treatment study: the effects of a cognitive remediation
      program on adolescents with early onset psychosis.
AB  - OBJECTIVE: To examine if a cognitive remediation program could be a positive
      supplement to a psychoeducational treatment program for adolescents with early
      onset psychosis. METHOD: Twenty-six subjects, randomly assigned to cognitive
      remediation (n = 14) or control group (n = 12), were assessed on cognitive,
      clinical, psychosocial and behavioural measures. RESULTS: No significant between
      group differences in pre- and post-treatment scores were found. This may be due
      to low statistical power. Exploratory within-group analyses showed that the
      training group improved on five of the 10 cognitive, and three of the five
      functioning outcome measures, while the control group improved on three of the
      cognitive, and one functioning outcome variable. CONCLUSION: Based on these
      results we cannot conclude that the addition of this cognitive remediation
      program, yields better results than psychoeducation alone. However, within-group
      analyses indicate that on specific cognitive functions, as well as on some
      functioning outcome measures, the remediation program may have a positive effect.

PMID- 14674962
TI  - Amphetamine-like stimulant cessation in an abusing patient treated with
      bupropion.
AB  - OBJECTIVE: Bupropion sustained release is considered to be a weak inhibitor of
      dopamine and serotonin reuptake. METHOD: We report the case of an amphetamine
      abusing patient who self-administered bupropion. RESULTS: Since 30 years, a 52
      year-old women used amphetamine derivates. She explained her need for amphetamine
      use in order to perform daily activities. Recently, she decided to experiment
      with bupropion. She abruptly stopped taking clobenzorex and simultaneously
      started taking bupropion (150 mg/day). The seventh day she reported a concomitant
      intake of clobenzorex; this induced adverse effects. Whilst taking bupropion, she
      described experiencing an euthymic state without any compulsion to take
      amphetamine drugs and was able to perform daily activities. After stopping it, no
      symptoms of withdrawal were reported by the patient. CONCLUSION: This observation
      supports an another report suggesting that bupropion may be of help in weaning
      from amphetamine users and should be confirmed by clinical trials.

PMID- 14674967
TI  - Comfortably numb?

PMID- 14674968
TI  - Brain injury after adult cardiac surgery.
AB  - Despite remarkable progress in surgical, cardiopulmonary bypass and anaesthetic
      techniques during the last three decades, brain damage remains an important
      complication of adult cardiac surgery. Effective brain protection strategies are
      already implemented today, but ongoing research is needed to meet the challenges
      faced in operating on increasingly old and disabled patients. The incidence of
      brain injury may be reduced by modifying the surgical procedure according to
      carotid duplex scanning and epiaortic echocardiography, by using techniques to
      reduce microembolization during cardiopulmonary bypass and by optimizing patient
      temperature during and after surgery. Increased knowledge will aid in choosing
      the best procedure or combination of procedures in each case to ensure that risks
      do not outweigh benefits.

PMID- 14674969
TI  - Reduction in the incidence of awareness using BIS monitoring.
AB  - BACKGROUND: Explicit recall (ER) is evident in approximately 0.2% of patients
      given general anaesthesia including muscle relaxants. This prospective study was
      performed to evaluate if cerebral monitoring using BIS to guide the conduction of
      anaesthesia could reduce this incidence significantly. PATIENTS AND METHODS: A
      prospective cohort of 4945 consecutive surgical patients requiring muscle
      relaxants and/or intubation were monitored with BIS and subsequently interviewed
      for ER on three occasions. BIS values between 40 and 60 were recommended. The
      results from the BIS-monitored group of patients was compared with a historical
      group of 7826 similar cases in a previous study when no cerebral monitoring was
      used. RESULTS: Two patients in the BIS-monitored group, 0.04%, had ER as compared
      with 0.18% in the control group (P < 0.038). Both BIS-monitored patients with ER
      were aware during intubation when they had high BIS values (> 60) for 4 min and
      more than 10 min, respectively. However, periods with high BIS = 4 min were also
      evident in other patients with no ER. Episodes with high BIS, 4 min or more, were
      found in 19% of the monitored patients during induction, and in 8% of cases
      during maintenance. CONCLUSIONS: The use of BIS monitoring during general
      anaesthesia requiring endotracheal intubation and/or muscle relaxants was
      associated with a significantly reduced incidence of awareness as compared with a
      historical control population.

PMID- 14674970
TI  - Age-related effects in the EEG during propofol anaesthesia.
AB  - BACKGROUND: Age-related differences in the spectral composition of the EEG in
      induction and emergence times, and in drug consumption during propofol
      anaesthesia were investigated. METHODS: The EEGs of 60 female patients between 22
      and 85 years of age were monitored continuously during standardized induction of
      anaesthesia with 2 mg of propofol kg(-1)60 s(-1). The EEGs were visually assessed
      in 20-s epochs according to a scale from A (awake) to F (very deep hypnosis).
      Visual EEG classifications, spectral parameters, and induction times were
      compared between different age groups. Additionally, data of 546 patients
      included in a multicentre study with 4630 patients (EEG monitor Narcotrend, MT
      MonitorTechnik, Bad Bramstedt, Germany) were analyzed with regard to age
      dependent changes of propofol consumption using target-controlled infusion (TCI).
      RESULTS: During induction, patients older than 70 years reached significantly
      deeper EEG stages than younger patients, needed a longer time to reach the
      deepest EEG stage, and needed more time until a light EEG stage was regained. In
      patients aged 70 years and older, the total power, mainly in deep EEG stages, was
      significantly smaller due to a distinctly smaller absolute power of the delta
      frequency band. No single spectral parameter was able to reliably distinguish all
      EEG stages. During the steady state of anaesthesia, older patients needed less
      propofol for the maintenance of a defined stage of hypnosis than younger
      patients. CONCLUSION: Older patients differ from younger ones regarding the
      hypnotic effect of propofol and the spectral patterns in the EEG. For an
      efficient automatic assessment of the EEG during anaesthesia a multivariable
      approach accounting for age-effects is indispensable.

PMID- 14674971
TI  - Propofol and remifentanil for intubation without muscle relaxant: the effect of
      the order of injection.
AB  - BACKGROUND: Common practice in intubation without muscle relaxant is to inject
      the opioid drug prior to the hypnotic drug. Because remifentanil reaches adequate
      cerebral concentration more rapidly than does propofol, we tested the hypothesis
      that injection of remifentanil after propofol might lead to better intubating
      conditions. METHODS: Thirty ASA I-II patients scheduled for elective surgery and
      with no anticipated difficult intubation were enrolled in the study. Five minutes
      after midazolam 30 microg kg(-1), patients were randomized into two groups: group
      PR received propofol 2.5 mg kg(-1) followed by remifentanil 1 microg kg(-1), and
      group RP received remifentanil 1 microg kg(-1) followed by propofol 2.5 mg kg(
      1). Intubating conditions were compared using a well-validated score, and
      continuous arterial pressure was recorded non-invasively. RESULTS: Compared with
      group RP, intubating conditions were significantly better in group PR. The mean
      arterial pressure decrease was more pronounced in group RP. CONCLUSIONS: We
      therefore conclude that in premedicated healthy patients with no anticipated risk
      of difficult intubation, intubating and haemodynamic conditions are better when
      remifentanil is injected after propofol.

PMID- 14674972
TI  - Pulmonary inflammatory mediators after sevoflurane and thiopentone anaesthesia in
      pigs.
AB  - BACKGROUND: Volatile anaesthetics have been shown to affect the release of
      pulmonary inflammatory mediators and exacerbate pulmonary injury after
      experimental aspiration. Thus, in theory, volatile anaesthetics may worsen
      inflammatory pulmonary injury and disease. We have previously described that no
      significant changes in alveolar ultrastructure are seen after sevoflurane
      anaesthesia. However, this does not exclude any possible physiological
      alterations. The aim of our study was to evaluate pulmonary inflammatory
      mediators in bronchoalveolar lavage (BAL) after sevoflurane and thiopentone
      anaesthesia in pigs with intact lungs. 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. Bronchoalveolar lavage samples were collected at the end of the study to
      determine pulmonary inflammatory markers. RESULTS: Compared with thiopentone
      anaesthesia, significant increases in BAL leukotriene C4 (LTC4), NO3-, and NO2-
      levels were observed after sevoflurane anaesthesia. In addition, there was a
      significant decrease in total blood leukocyte count in sevoflurane-treated
      animals. CONCLUSION: We conclude that sevoflurane increases pulmonary LTC4, NO3-,
      and NO2- production in pigs, indicating an inflammatory response.

PMID- 14674973
TI  - Haemodynamic effects of volume resuscitation by hypertonic saline-dextran (HSD)
      in porcine acute cardiac tamponade.
AB  - BACKGROUND: Hypertonic saline-dextran (HSD) has been utilized for small-volume
      resuscitation in acute circulatory shock. However, HSD has also been reported to
      induce myocardial depression. The aim of this study was to examine the effects of
      HSD on cardiac performance and splanchnic perfusion in a low cardiac output model
      based on experimental cardiac tamponade. METHODS: Seven anaesthetized,
      mechanically ventilated pigs of both sexes (weight 24 +/- 2 kg, mean +/- SEM)
      completed a randomized, cross-over protocol. A low cardiac output state was
      established by intrapericardial infusion of dextran. Animals were resuscitated by
      bolus infusions (4 ml kg(-1) in 2 min) of either 7.5% hypertonic saline-dextran
      or Ringer's acetated solution (RAc) and then observed during tamponade (20 min)
      and following its release (40 min). Central haemodynamics, portal venous (QPV)
      and renal arterial (QRA) flows were measured together with gastric, jejunal,
      hepatic and renal laser-Doppler flowmetry. RESULTS: Resuscitation using HSD in a
      low cardiac output state completely restored QPV and improved gastric, jejunal,
      hepatic and renal microcirculation as assessed by laser-Doppler flowmetry while
      no significant effect was observed in QRA. No such beneficial effects could be
      observed when animals were resuscitated using RAc. The improved haemodynamic
      state by HSD was maintained following release of cardiac tamponade while
      perfusion in RAc resuscitated animals returned to baseline or even remained
      depressed (hepatic and renal microcirculation). No signs of cardiodepression by
      HSD were observed. CONCLUSION: Resuscitation using HSD in a low cardiac output
      state restored splanchnic perfusion and microcirculation without any signs of
      cardiodepression.

PMID- 14674974
TI  - Results and costs of intensive care in a tertiary university hospital from 1996
      2000.
AB  - BACKGROUND: Costs of intensive care may be 20% of all hospital costs. Population
      aging likely increases the demand for intensive care services, while health care
      has financial limitations. Therefore data about outcome and costs of intensive
      care are needed. We studied changes in patient characteristics, outcome,
      intensity of care and costs of intensive care in a tertiary university hospital
      in Finland. METHODS: We analyzed retrospectively data of patients admitted to the
      ICU between 1 January 1996 and 31 December 2000 using the patient data management
      system. Postoperative and ICU patients were analyzed separately. Data included
      age, Apache II score, cause of intensive care admission, length and intensity of
      ICU care. ICU, hospital and 6-month mortality were analyzed. Intensity of care
      was assessed by TISS points and the annual costs of intensive care were
      evaluated. RESULTS: The number of ICU admissions from 1996-2000 was 11,323. The
      proportions of ICU and postoperative patients were 39% and 61%, respectively. The
      mean age of the patients did not change. The mean Apache II score increased over
      time both in the ICU and postoperative patients. There was no change in crude
      hospital mortality. Total ICU costs decreased from 8,660,000 euros (in 1997) to
      7,480,000 euros (in 2000). In the ICU patients, the costs of hospital survival
      decreased towards the end of the study period. CONCLUSIONS: We treated more
      severely ill patients with unchanged outcome but at lower costs towards the end
      of the study period. Costs of intensive care are not necessarily increasing.

PMID- 14674975
TI  - Ventriculo-arterial coupling and mechanical efficiency with remifentanil in
      patients with coronary artery disease.
AB  - BACKGROUND: Optimum transfer of energy from the left ventricle to the arterial
      circulation requires appropriate matching of these mechanical systems. Left
      ventricular-arterial coupling describes this relationship between the ventricular
      elastance (Ees) and arterial elastance (Ea). The ratio of these elastances
      defines the efficiency of myocardium and provides in our study a useful technique
      for assessment of the actions of remifentanil. The purpose of this study was to
      evaluate the effects of remifentanil on ventriculo-arterial coupling in cardiac
      surgery in patients with coronary artery disease. METHODS: Fourteen patients with
      coronary artery disease, submitted intraoperatively to cardiac anesthesia for
      myocardial revascularization, were examined prospectively. With the use of
      transesophageal echocardiography (TEE) and different dicrotic arterial pressures,
      we determined the ventricle elastance (Ees), the arterial elastance (Ea) and
      myocardial efficiency before and after administration of a slow-bolus of
      remifentanil (1 micro kg(-1)). RESULTS: Remifentanil decreases significantly the
      ventricular elastance (from 6.09 mmHg ml-1 m(-2) to 4.88) (P < 0.05), with a
      less, but however, significant decrease of arterial elastance (from 3.68 mmHg ml(
      1) m(-2) to 3.13) (P < 0.05). Despite causing simultaneous declines, maintains a
      good myocardial efficiency (0.64-0.68) with no significant difference.
      CONCLUSION: Although remifentanil depresses ventricular and arterial elastance,
      preserves a good left ventricular-arterial coupling and mechanical efficiency,
      despite a little increase of coupling. However, these effects are maintained only
      during a slow intravenous infusion and are dose-dependent with impairment of
      coupling, that may contribute to decline in overall cardiovascular performance,
      at higher anesthetic dose and rapid infusion in patients with a severe myocardial
      dysfunction.

PMID- 14674976
TI  - Fluid challenge in patients at risk for fluid loading-induced pulmonary edema.
AB  - BACKGROUND: This study evaluated the effects of protocol-guided fluid loading on
      extravascular lung water (EVLW) and hemodynamics in a group of patients at high
      risk for volume expansion-induced pulmonary and systemic edema. METHODS: Nine
      acutely admitted septic patients with acute lung injury (ALI) were prospectively
      studied. In addition to sepsis and ALI, the following criteria indicating
      increased risk for edema formation had to be fulfilled: increased vascular
      permeability defined as microalbuminuria greater than fivefold normal and
      hypoalbuminemia < 30 g l(-1). Two hundred-ml boluses of a 10% hydroxyethyl starch
      (HES) was titrated to obtain best filling pressure/stroke volume relation.
      Extravascular lung water and intrathoracic blood volume (ITBV) were measured
      using a transpulmonary double-indicator dilution technique. Baseline data were
      compared with data at the end of fluid loading and 3 h postchallenge. RESULTS: At
      study entry the mean EVLW was 13 ml kg(-1), and the mean EVLW/ITBV ratio
      (indicator of pulmonary permeability) was 0.72 (normal range 0.20-0.30). To
      attain optimal preload/stroke volume relation 633 +/- 240 ml of HES was needed.
      Fluid loading significantly increased preload (CVP, PAOP and ITBV), and stroke
      volume. Effective pulmonary capillary pressure (Pcap) rose only slightly. As a
      result, the Pcap-PAOP gradient decreased. Despite increased cardiac output, EVLW
      did not change by plasma expansion. CONCLUSION: In this selected group of at-risk
      patients, the optimization of cardiac output guided by the concept of best
      individual filling pressure/stroke volume relationship did not worsen
      permeability pulmonary edema.

PMID- 14674977
TI  - Complement activation, endothelin-1 and neuropeptide Y in relation to the
      cardiovascular response to endotoxin-induced systemic inflammation in healthy
      volunteers.
AB  - BACKGROUND: Endotoxin is a major stimulus for triggering the host response in
      septicaemia. The pathophysiology of sepsis involves activation of the vascular
      endothelium and leukocytes, resulting in the release of various mediators, e.g.
      cytokines, nitric oxide (NO), endothelin (ET-1) and complement factors. We
      evaluated the blood levels of complement activation, ET-1 and neuropeptide Y
      (NPY) in parallel with the haemodynamic and oxygen transport response during
      human experimental endotoxemia. METHODS: Eleven healthy men had venous, arterial
      and pulmonary arterial catheters placed for continuous haemodynamic measuring.
      After 30 min rest endotoxin (E. Coli 4 ng kg(-1), Lot G1) was intravenously
      administered. Blood samples from pulmonary and arterial catheters were collected
      hourly over 4 h. RESULTS: Body temperature augmented significantly from baseline
      values (36.7 +/- 0.7 degrees C, mean +/- SEM) with a maximum after 3.5 h (39.1 +/
      0.3 degrees C, P < 0.001). Cardiac output increased by 100%, systemic vascular
      resistance decreased by 50%, the oxygen consumption and the tissue oxygen
      transport increased. Activation of the complement system was indicated by an
      increase in SC5b-9. Endothelin-1-like immunoreactivity (ET-1-LI) increased over
      time in arterial blood. NPY-like immunoreactivity (NPY-LI) did not change over
      time. CONCLUSION: A dose of endotoxin associated with reproducible systemic
      vasodilation and fever in healthy subjects causes complement activation and
      increased systemic levels of ET-1-LI, illustrating that the model is a useful
      tool for inducing moderate systemic inflammation where several mediator systems
      are activated.

PMID- 14674978
TI  - Effects of end-inspiratory and end-expiratory pressures on alveolar recruitment
      and derecruitment in saline-washout-induced lung injury -- a computed tomography
      study.
AB  - BACKGROUND: Lung protective ventilation using low end-inspiratory pressures and
      tidal volumes (VT) has been shown to impair alveolar recruitment and to promote
      derecruitment in acute lung injury. The aim of the present study was to compare
      the effects of two different end-inspiratory pressure levels on alveolar
      recruitment, alveolar derecruitment and potential overdistention at incremental
      levels of positive end-expiratory pressure. METHODS: Sixteen adult sheep were
      randomized to be ventilated with a peak inspiratory pressure of either 35 cm H2O
      (P35, low VT) or 45 cm H2O (P45, high VT) after saline washout-induced lung
      injury. Positive end-expiratory pressure (PEEP) was increased in a stepwise
      manner from zero (ZEEP) to 7, 14 and 21 cm of H2O in hourly intervals. Tidal
      volume, initially set to 12 ml kg(-1), was reduced according to the pressure
      limits. Computed tomographic scans during end-expiratory and end-inspiratory hold
      were performed along with hemodynamic and respiratory measurements at each level
      of PEEP. RESULTS: Tidal volumes for the two groups (P35/P45) were: 7.7 +/-
      0.9/11.2 +/- 1.3 ml kg(-1) (ZEEP), 7.9 +/- 2.1/11.3 +/- 1.3 ml kg(-1) (PEEP 7 cm
      H2O), 8.3 +/- 2.5/11.6 +/- 1.4 ml kg(-1) (PEEP 14 cm H2O) and 6.5 +/- 1.7/11.0 +/
      1.6 ml kg(-1) (PEEP 21 cm H2O); P < 0.001 for differences between the two
      groups. Absolute nonaerated lung volumes during end-expiration and end
      inspiration showed no difference between the two groups for given levels of PEEP,
      while tidal-induced changes in nonaerated lung volume (termed cyclic alveolar
      instability, CAI) were larger in the P45 group at low levels of PEEP. The
      decrease in nonaerated lung volume was significant for PEEP 14 and 21 cm H2O in
      both groups compared with ZEEP (P < 0.005). Over-inflated lung volumes, although
      small, were significantly higher in the P45 group. Significant respiratory
      acidosis was noted in the P35 group despite increases in the respiratory rate.
      CONCLUSION: Limiting peak inspiratory pressure and VT does not impair alveolar
      recruitment or promote derecruitment when using sufficient levels of PEEP.

PMID- 14674979
TI  - The effect of carbon dioxide, respiratory rate and tidal volume on human heart
      rate variability.
AB  - BACKGROUND: Heart rate variability (HRV) has been used for assessment of depth of
      anesthesia. Alterations in respiratory rate and tidal volume modulate the
      sympatovagal neural drive to the heart. The changes in PaCO2 that accompany
      changes in breathing pattern may, through chemoreceptors in the brainstem,
      independently influence the autonomic control of the heart and modulate HRV.
      METHODS: We measured the effects of PaCO2, tidal volume and respiratory rate on
      HRV during spontaneous and mechanical ventilation in 22 healthy volunteers and in
      25 mechanically ventilated anesthetized patients. RESULTS: Adding CO2 to the
      inspiratory gas increased high frequency (HF) and low frequency (LF) components
      of HRV in awake volunteers both during spontaneous and mechanical ventilation,
      while this effect of CO2 was abolished in patients during anesthesia. Increase of
      tidal volume increased HF component of HRV only in volunteers during spontaneous
      ventilation. On the other hand, when respiratory rate was reduced, the balance of
      HF and LF power moved toward LF power in all study groups. Breathing frequency
      altered HRV independent on PaCO2, tidal volume and the level of consciousness. In
      contrast, the effect of PaCO2 appeared to be related to normal level of
      consciousness, suggesting that a cortical modulation of the autonomic nervous
      activity contributes to the effects of PaCO2 on HRV. CONCLUSIONS: PaCO2, tidal
      volume and respiratory rate should be controlled when HRV power spectrum is
      measured in conscious patients or volunteers, while in anesthetized patients
      small changes in end-tidal CO2 or tidal volume do not modulate HRV if respiratory
      rate remains unchanged.

PMID- 14674980
TI  - Direct myocardial depressant effect of naloxone: mechanical and
      electrophysiological actions in vitro.
AB  - BACKGROUND: Naloxone, an opioid antagonist, has a cardiovascular pressor effect
      and has been used in various types of shock states. The aim was to determine the
      non-opioid effect on direct cardiac muscle contractility and explore the
      mechanism using guinea pig right ventricular papillary muscles. METHODS: With
      institutional approval, isometric contractile force was measured in modified
      normal and 26 mM K+ Tyrode solution at various stimulation rates. The effects of
      naloxone on sarcoplasmic recticulum function were evaluated by measuring rested
      state contraction in low Na+ (25 mM) Tyrode solution and rapid cooling
      contracture in modified normal Tyrode solution. Normal and slow action potentials
      (APs) were measured using conventional microelectrode technique. Patch clamp
      study was performed to examine the direct effect on Ca2+ current in cardiac
      ventricular myocytes. RESULTS: Naloxone (50, 100, and 200 microM) caused a
      concentration-dependent depression of peak force and maximal rate of force
      development. Modest depression, approximately 20%, was shown in rested-state
      contraction in low Na+ Tyrode solution. Naloxone (100 microM) modestly depressed
      the rapid cooling contracture to 80 +/- 3% of baseline, accompanied by
      prolongation of time to peak contracture by approximately 37%. In 26 mM K+ Tyrode
      solution, naloxone (100 microM) markedly and selectively depressed the late force
      development. While naloxone (100 microM) did not alter the amplitude and dV/dt
      max in normal and slow APs at 0.25 Hz, AP duration was prolonged significantly.
      In patch clamp experiment, naloxone (50 microM) depressed Ca2+ current by
      approximately 50%. CONCLUSIONS: The direct myocardial depressant effect of
      naloxone appeared to be in part caused by depression of Ca2+ influx through
      cardiac membrane. Sarcoplasmic reticulum function appeared to be modestly
      depressed.

PMID- 14674982
TI  - Bier's block; 100 years old and still going strong!
AB  - In August 1908 Karl August Bier, Professor of Surgery in Berlin, described a new
      method of producing analgesia of a limb which he named 'vein anesthesia'. Bier
      first presented his new method of intravenous regional anesthesia (IVRA) at the
      37th Congress of the German Surgical Society on 22 April, 1908, only 10 years
      after his significant communication on spinal anesthesia (1). His method, which
      now bears his name, consisted of occluding the circulation in a segment of the
      arm with two tourniquets and then injecting a dilute local anesthetic through a
      venous cut-down in the isolated segment. Bier had the good fortune to use
      procaine, the first safe injectable local anesthetic that had been synthesized by
      Einhorn in 1904.

PMID- 14674981
TI  - Chronic pain following Caesarean section.
AB  - BACKGROUND: Chronic postoperative pain is a well-recognized problem after various
      types of surgery such as amputation, thoracotomy, mastectomy, gallbladder surgery
      and inguinal hernia repair. However, little is known about chronic pain after
      gynaecologic surgery. Therefore, the aim was to study the incidence of chronic
      pain after Caesarean section. METHODS: A questionnaire was sent in February/March
      2003 to 244 consecutive patients who underwent Caesarean section in a one-year
      period from 1 October 2001 to 30 September 2002. Patients were asked about
      duration of postoperative abdominal scar pain, and if pain was still present to
      describe the frequency and intensity of pain and its impact on daily life. The
      questionnaire also included questions about the Caesarean section and about pain
      problems elsewhere. RESULTS: A total of 220 patients (90.2%) answered the
      questionnaire. The mean follow-up time was 10.2 months (range 6-17.6).
      Postoperative pain resolved in most patients within 3 months but 27 patients
      (12.3%) still had pain at the time of the interview. No patients had constant
      pain, but in 13 of 27 patients (5.9%) pain was present daily or almost daily.
      Patients with persistent pain (n = 27) had more often undergone general than
      spinal anaesthesia for the Caesarean section. Frequencies of pain problems
      elsewhere and recalls of severe acute postoperative pain were also higher among
      patients with persistent pain. CONCLUSION: Chronic pain after Caesarean section
      seems to be a significant problem in at least 5.9% of patients.

PMID- 14674983
TI  - Pneumomediastinum in labour -- probably not caused by a lumbar epidural
      anaesthesia.
AB  - We describe a case of pneumomediastinum and subcutaneous emphysema during labour.
      The patient had previously received an epidural anaesthesia to alleviate labour
      pain. We found several reports of subcutaneous emphysema and pneumomediastinum
      (or pneumothorax) possibly caused by or related to epidural anaesthesia use, but
      conclude that the epidural anaesthesia was probably not a cause in our case.

PMID- 14674984
TI  - Bilateral occipital neuropathy as a rare complication of positioning for thyroid
      surgery in a morbidly obese patient.
AB  - BACKGROUND: Peripheral neuropathies in various locations are described as
      complications after anesthesia and surgery. This is the first case report of
      temporary bilateral occipital neuropathy from positioning for thyroid surgery in
      a morbidly obese patient. METHODS: A 48-year-old women with a history of
      depression, fibro-myalgia, asthma, sleep apnea, diabetes mellitus and morbid
      obesity (127 kg, 165 cm) underwent 4 hours anesthesia with propofol/remifentanil
      without muscle relaxation for thyroid surgery. The neck with a very low range of
      motion secondary to fat tissue needed to be extended to facilitate surgery as
      much as possible. The head was carefully padded and there were no episodes of
      hypotension or hypoxemia throughout the case or in the PACU. At post op day 1 she
      complained of bilateral numbness in the distribution area of both greater
      occipital nerves. On post op day 2 tingling sensations and improvement of
      numbness was noticed. The patient recovered without residual symptoms after 6
      weeks. CONCLUSION: Pressure or shear stress to the nerve, hypoperfusion or
      metabolic disturbances are discussed as the leading etiology of nerve damage
      during surgery in the literature. Pressure from fat tissue during prolonged head
      extension for surgery seems to be the cause in this case and should therefore be
      avoided whenever possible in morbidly obese patients, especially when other risk
      factors for neuropathy like diabetes are present.

PMID- 14674985
TI  - Tetrodotoxin-induced conduction blockade is prolonged by hyaluronic acid with and
      without bupivacaine.
AB  - BACKGROUND: In isolated nerves, tetrodotoxin (TTX) blocks nerve conduction longer
      than bupivacaine. In vivo, however, both substances block nerve conduction to an
      equal duration, presumably because the hydrophilic TTX binds only weakly to the
      perineural tissue. High molecular weight hyaluronic acid (HA) prolongs the action
      of local anaesthetics several-fold. We tested whether admixture of HA enhances
      the binding of TTX to the perineural tissue and thus induces an ultra-long
      conduction block after a single application. METHODS: In 12 anaesthetized
      rabbits, the minimal blocking concentrations of TTX, TTX and HA (TTX/HA) and
      bupivacaine with HA (bupivacaine/HA) were determined by blocking the natural
      spike activity of the aortic nerve. In 18 other animals, equipotent
      concentrations of either TTX, TTX/HA or TTX/bupivacaine/HA were applied topically
      to the aortic nerve. After disappearance of the spike activity, the wound was
      closed to simulate the clinical situation of a single shot nerve block. The time
      until recovery of spike activity was determined. The nerves were examined for
      signs of neurotoxicity 24 h after the application of the drugs. Data are
      presented as means +/- SD and compared by ANOVA and Student's t-test for unpaired
      data. RESULTS: The conduction block by TTX/bupivacaine/HA (10.1 +/- 1.9 h) or
      TTX/HA (9.3 +/- 1.0 h) was significantly longer than that of plain TTX (7.9 +/-
      1.0 h). Neurotoxicity was not observed. CONCLUSIONS: Both HA and HA/bupivacaine
      prolong the TTX-induced conduction blockade of the aortic nerve of rabbits in
      vivo. No signs of neurotoxicity were observed.

PMID- 14674986
TI  - Loco-regional anaesthesia for a total knee arthroplasty in a high-risk cardiac
      patient.

PMID- 14674987
TI  - Thoracic outlet syndrome and anaesthetic problems.

PMID- 14674988
TI  - Characterization of smooth muscle components in renal angiomyolipomas:
      Histological and immunohistochemical comparison with renal capsular leiomyomas.
AB  - The smooth muscle components of angiomyolipoma (AML) of the kidney have a wide
      histological and immunohistochemical spectrum. In the present study, 50 cases of
      AML and seven cases of renal capsular leiomyoma (RCL) were reviewed
      histologically and immunohistochemically, and the results compared with those of
      leiomyomas of soft parts. The AML cases were subclassified into 34 cases of
      common, 12 of leiomyomatous and four of lipomatous type. Even the common-type AML
      tissues showed a variety of histologic features, including lymphangiomyoma. The
      cytoplasm of leiomyomatous cells in AML was usually plump and eosinophilic, but
      sometimes clear with abundant glycogen, and an ovoid or irregular cleaved
      nucleus. AML cells, irrespective of whether they were epithelioid or
      leiomyomatous, stained positively for HMB45, S100 protein, and alpha-smooth
      muscle actin. RCL cells had histologic features identical to those of the
      leiomyomatous cells in AML. Moreover, the immunohistochemical profiles of the RCL
      cells were also identical to those of AML. These morphologic and
      immunohistochemical findings are different from those of smooth muscle tumors in
      soft parts and confirm that AML and RCL are closely related proliferative
      entities.

PMID- 14674989
TI  - Inactivation of the PTEN gene protein product is associated with the invasiveness
      and metastasis, but not angiogenesis, of breast cancer.
AB  - PTEN is a novel tumor-suppressor gene located on chromosomal band 10q23. Loss of
      PTEN function has been implicated in the progression of several types of cancer,
      but the correlation between loss of PTEN expression and advanced carcinomas is
      not well established. The capacity for angiogenesis of a tumor is known to play a
      very important role in growth and metastasis, and there have been reports that
      PTEN relates to angiogenesis. In the present study, formalin-fixed and paraffin
      embedded tissues from 101 patients with breast carcinomas, including 88 cases of
      invasive ductal carcinomas and 13 cases of ductal carcinoma in situ (DCIS), were
      evaluated by immunohistochemical methods for the expression of PTEN and vascular
      endothelial growth factor (VEGF), as well as microvessel density (MVD). The
      results were compared with the clinicopathologic parameters. There was no loss of
      PTEN expression in any of the cases of DCIS, but 28 (32%) of the 88 invasive
      cases did not express PTEN. Loss of PTEN expression was associated with lymph
      node metastasis (P = 0.03), but did not correlate with tumor size, tumor grade,
      MVD or recurrence. VEGF expression significantly correlated with lymph node
      metastasis in invasive ductal carcinoma (P = 0.01). There was no correlation
      between the expression of PTEN and that of VEGF (P = 0.63). The present study
      suggests that loss of PTEN expression is common and correlates with tumor
      progression and lymph node metastasis in breast carcinoma. The relationship
      between loss of PTEN and progression of breast cancer may not be explained by
      modulation of angiogenesis.

PMID- 14674990
TI  - No evidence of a correlation between BCL10 expression and API2-MALT1 gene
      rearrangement in ocular adnexal MALT lymphoma.
AB  - In the present study, 62 cases of ocular adnexal lymphoproliferative disorders
      were reviewed clinicopathologically. Of them, 51 were extranodal marginal zone B
      cell lymphoma (MALT lymphoma), five were diffuse large B-cell lymphoma (DLBCL),
      one was peripheral T-cell lymphoma, one was NK/T cell lymphoma, nasal type, and
      four were reactive lymphoid hyperplasia. These lymphoma cases showed a favorable
      clinical course and localized disease, except for the case of NK/T cell lymphoma,
      although 19 cases (32.8%) had a recurrence of disease. To clarify the correlation
      between BCL10 protein expression and API2-MALT1 gene rearrangement, the 51 cases
      of MALT lymphoma and 5 cases of DLBCL were analyzed by immunohistochemical and RT
      PCR methods. Nuclear BCL10 expression was identified in 58% of MALT lymphoma
      cases, but not in any DLBCL cases. There was no evidence of a correlation between
      aberrant nuclear BCL10 expression and the clinical parameters examined in the
      present study. API2-MALT1 transcription was not demonstrated in either the MALT
      lymphoma cases or the DLBCL cases studied using a multiplex one-tube reverse
      transcriptase-PCR method. These findings indicate that the nuclear expression of
      BCL10 is unlikely to correlate with the API2-MALT1 fusion gene in ocular adnexal
      MALT lymphoma.

PMID- 14674991
TI  - Human DNA damage checkpoints and their relevance to soft tissue sarcoma.
AB  - Soft tissue sarcoma (STS) is a malignant neoplasm, arising in mesenchymal
      tissues, that is difficult to treat clinically because it can be highly resistant
      to chemo-radiotherapy. At present, the mechanism of that resistance remains
      unclear. Cell cycle checkpoints engender strict control of cell proliferation,
      arresting the cell cycle to provide time for repair or apoptosis when DNA damage
      is induced by unprogrammed extrinsic events. These pathways involve at least two
      checkpoints: one at the G1/S transition and one at the G2/M transition. The p53
      gene, which is mutated in several malignant tumors, plays an important role in
      DNA repair at the G1/S transition; however, there is little information on the
      G2/M checkpoint in STS. In the present study, several proteins (phospho-p53, 
      cdc25, -cdc2, -Chk1 and -Chk2) involved in checkpoint pathways were investigated
      using immunohistochemistry in STS specimens. Most STSs maintain a well-preserved
      G2/M checkpoint despite the loss of the G1/S checkpoint (phospho-p53: 4.9%
      (2/41); -cdc25: 41% (17/41); -cdc2: 61% (25/41); -Chk1: 29% (12/41); -Chk2: 46%
      (19/41)). Furthermore, in a postoperative chemotherapy case the number of cells
      positive for phospho-cdc25 and -Chk2 was higher in a recurrent tumor than in the
      primary tumor (n = 7, P = 0.046 < 0.05, Wilcoxon signed-ranks test). These
      findings indicate that the G2/M checkpoint pathway is well preserved and might
      contribute to the chemotherapeutic resistance associated with STS.

PMID- 14674992
TI  - Deposition of IgD, alpha-1-antitrypsin and alpha-1-antichymotrypsin on Demodex
      folliculorum and D. brevis infesting the pilosebaceous unit.
AB  - A total of seven routinely processed biopsy specimens of facial skin lesions with
      infestation of Demodex folliculorum or D. brevis were immunostained for plasma
      proteins and secretory proteins. The cuticular layer of the mites located within
      the pilosebaceous unit was selectively immunoreactive for IgD (delta chain),
      alpha-1-antitrypsin and alpha-1-antichymotrypsin. Negative results were obtained
      for IgG, IgA, IgM, IgE, albumin, fibrinogen, C3, amyloid P component, prealbumin,
      lysozyme and lactoferrin. These findings suggest a novel function of IgD and
      serum protease inhibitors as a protective host response to the mite.

PMID- 14674993
TI  - Expressions of junB and c-fos are enhanced in 4-nitroquinoline 1-oxide-induced
      rat tongue cancers.
AB  - Activator protein-1 (AP-1) is a transcription factor activated in many tumors.
      Using 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue cancers (TC), the
      present study investigated the expression levels of genes that encode the
      components of AP-1, the jun gene family (c-jun, junB and junD) and the fos gene
      family (c-fos, fra-1, fra-2 and fosB). Expression levels of junB and c-fos mRNAs
      in TC were significantly elevated compared with those in epithelial tissue of
      control rat tongue, although only c-fos mRNA levels tended to be elevated in
      dysplastic tongue epithelium. Histologically, all 4NQO-induced rat TC were well
      differentiated squamous cell carcinomas. Immunostaining for JunB and c-Fos
      proteins was positive in the nuclei of tumor cells of all TC. It is noteworthy
      that JunB was negative, but c-Fos was positive in the dysplastic tongue
      epithelium of the 4NQO-treated rats. Immunostaining for both proteins was
      negative in tongue mucosal epithelium of control rats. There were no mutations in
      the coding regions of either junB or c-fos in all the TC examined. These results
      suggest the possibility that the expressions of junB and c-fos were enhanced
      stepwise in 4NQO-induced carcinogenesis of rat tongue, and that the coexpression
      of JunB and c-Fos might play an important role in the establishment of TC.

PMID- 14674994
TI  - Adult-onset familial pulmonary fibrosis in Japanese brothers.
AB  - Two Japanese brothers were diagnosed in their 20s with familial pulmonary
      fibrosis, the pathological findings of which were consistent with usual
      interstitial pneumonia (UIP). However, an atypical characteristic was observed in
      the lungs of these brothers; 2-mm areas of 'honeycomb' were identified throughout
      the lungs, which is smaller than the generally observed 5-10 mm honeycombing seen
      in UIP. Fibroblastic foci were demonstrated in the second eldest brother, but not
      in the eldest, which indicates that the lungs of the eldest brother was in a more
      advanced stage of fibrosis. Their youngest brother and parents have no clinical
      evidence of pulmonary fibrosis. All five family members had low values for the
      diffusion capacity of the lung for carbon monoxide (DLCO), suggesting the
      presence of an inheritable disease and the existence of different phenotypes. The
      genomic DNA of the affected brothers was sequenced for the reported surfactant
      protein C (SP-C) gene mutations in patients with familial pulmonary fibrosis, but
      none was documented. It is necessary to clarify the presence of novel gene
      mutations of SP-C or other genes to explain these particular pathological
      findings and the low DLCO observed in this family.

PMID- 14674995
TI  - Multifocal granular cell tumors of the gastrointestinal tract:
      Immunohistochemical findings compared with those of solitary tumors.
AB  - Granular cell tumors (GCT) are infrequently found in the gastrointestinal tract
      (GIT), and only four previous reports have described lesions occurring
      simultaneously in different sites. The present case of 11 GCT, located in the
      esophagus, stomach, colon and pericolic adipose tissue, occurred in a 50-year-old
      Japanese woman. All GCT appeared histologically benign and there was no sign of
      recurrence at 3 years after surgery. Immunohistochemical analysis and comparison
      between this case of multifocal GCT and six cases of solitary benign GCT of the
      GIT, which were taken from the files of the Department of Pathology at Kitasato
      University (1986-2000), demonstrated the follow-ing: (1) all diffusely expressed
      S-100, DCC and bcl-2, and (2) median labeling indices for Ki-67, cyclin D1, p53
      (Pab1801), and p21WAF1/CIP1 of 4%, 24%, 1% and 28%, respectively, for the
      multifocal tumors, and 3.5%, 23%, 1% and 29%, respectively, for the solitary
      lesions, with no significant difference between the two groups. Thus, the
      expression of cyclin D1 and p21WAF1/CIP1 may be involved in the tumorigenesis of
      both types of GCT. The present case emphasizes the need to evaluate the entire
      GIT when a single GCT is identified. Multifocal lesions should be treated
      conservatively by local excision because, as with the solitary tumors, they
      exhibit a benign biological behavior, consistent with their low Ki-67
      immunoreactivity.

PMID- 14674996
TI  - Hepatoid adenocarcinoma of the gallbladder: Case report and review of the
      literature.
AB  - A rare case of hepatoid adenocarcinoma (HAC) of the gallbladder occurred in a 72
      year-old man who presented with abdominal pain and was admitted to hospital.
      Ultrasonography and computed tomography revealed a mass in the gallbladder,
      multiple nodules in the liver and enlargement of the lymph nodes. He was
      diagnosed as having a gallbladder carcinoma with multiple liver and lymph node
      metastases. Cholecystectomy and partial hepatectomy was performed.
      Histologically, most of the mass in the gallbladder was composed of cells with
      eosinophilic cyto-plasm arranged in a trabecular pattern, which resembled
      hepatocellular carcinoma, but there was a component of well-differentiated
      adenocarcinoma in the mucosa. Immunohistochemically these hepatoid tumor cells
      were positive for Hepatocyte (Hepatocyte Paraffin 1: Hep Par1), which is
      considered highly sensitive and highly specific for hepatocyte differentiation.
      Based on these findings, this case was diagnosed as hepatoid adenocarcinoma of
      the gallbladder, which is generally a vary rare neoplasm in the literature, but
      should be included in the differential diagnosis of a mass in the gallbladder.

PMID- 14674997
TI  - Distribution of myofibroblastic cells in the liver and kidney of Meckel-Gruber
      syndrome.
AB  - Meckel-Gruber syndrome (MGS) is a rare disorder characterized by occipital
      encephalocele, polydactyly and polycystic kidney. Early diagnosis is very
      important because MGS has a high risk of recurrence and infants with MGS are
      frequently stillborn or die soon after birth. An autopsy case of MGS is presented
      and the focus is specifically on the myofibroblastic cells of the liver and
      polycystic kidney. Although routine histological examination did not reveal
      hepatic fibrosis, a specific distribution of alpha smooth muscle actin (alpha
      SMA)-positive and h-caldesmon (h-CD)-negative stromal cells (myofibroblastic
      cells) was observed along the limiting plate of the portal area. Furthermore,
      myofibroblastic cells were focally distributed along the sinusoidal wall and
      around the bile ducts in the portal area. In the polycystic kidney, the presence
      of myofibroblastic cells in the stroma between the cystic lesions was also
      confirmed by electron microscopy. In conclusion, myofibroblastic cells were
      distributed in the liver and kidney of a patient with MGS and their specific
      distribution in the liver may be indicative of prestage hepatic fibrosis.

PMID- 14674998
TI  - Mixed papillary adenocarcinoma and transitional cell carcinoma of the uterine
      cervix.
AB  - A mixed papillary adenocarcinoma and transitional cell carcinoma (MAcTcc) was
      discovered in the uterine cervix of a 38-year-old woman. A condylomatous
      papillary lesion was found in the uterine cervix during a colposcopic study and
      histopathological examination showed that the tumor was composed of two different
      neoplastic subtypes. One was an adenocarcinoma (AC) component showing papillary
      and tubular structure with endocervical and intestinal differentiation; the other
      was a transitional cell carcinoma (TCC) component showing papillary excrescence
      mimicking papillary TCC of urothelial origin. To characterize the tumor, an
      immunohistochemical study of cytokeratins (CK) was performed. The AC component
      showed immunoreactivities similar to conventional adenocarcinomas: positive
      immunoreactivity of low-molecular-weight cytokeratins 7, 8 and 19, and negative
      immunoreactivity of CK20 and high-molecular-weight cytokeratin (34betaE12). The
      lower epithelial layer of the TCC component showed different immunoreactivity,
      but the superficial epithelial layer had similar immunohistochemical findings to
      the AC component. These findings indicate that the TCC component had the cellular
      character of AC rather than that of TCC or squamous cell carcinomas. This is
      thought to be the first report of a MAcTcc of the uterine cervix.

PMID- 14674999
TI  - Deciduoid mesothelioma in the pelvic cavity.
AB  - A very rare case of deciduoid mesothelioma in the pelvic cavity is presented. A
      24-year-old woman (gestational stage: 28 weeks and 6 days) was admitted because
      of a tumor mass in the abdominal cavity. A well-circumscribed and fibrously
      encapsulated tumor mass was revealed in the Douglas cavity. Histologically, tumor
      cells were arranged in a solid sheet with deciduoid appearance and showed partial
      glandular and papillary structures. The tumor cells contained PAS positive and
      diastase-digested granules in the cytoplasm as well as alcian-blue positive and
      hyaluronidase-digested substances in the stroma. The cellularity of the tumor
      cells was moderate and mitoses were rare. There was partial tumor necrosis and
      tumor cells had infiltrated through the fibrous capsule. Immunohistochemically,
      the tumor cells were reactive for pancytokeratin, cytokeratin5/6, vimentin, HBME
      1, calretinin and thrombomodulin. Ultrastructurally, numerous, long microvilli,
      tonofilaments and desmosome junctions could be seen. Consequently, this case was
      diagnosed as deciduoid mesothelioma and 2 years and 4 months after operation, the
      patient's clinical course has been good. This case is considered to be the first
      reported in Japan.

PMID- 14675001
TI  - The rationale for nontransvenous leads and cardiac resynchronization devices.

PMID- 14675000
TI  - Primary leiomyosarcoma of the vertebra: Case report and review of the literature.
AB  - A case of primary leiomyosarcoma of a thoracic vertebra associated with a
      compression fracture in a 75-year-old woman was preoperatively thought to be
      granulation tissue. Surgical decompression was performed and the histological and
      immunohistochemical studies established the diagnosis of leiomyosarcoma. Based on
      the clinical and radiological examinations, metastases were ruled out. Primary
      leiomyosarcoma of the vertebra is extremely rare and in that site it is
      considered to have a relatively poor prognosis.

PMID- 14675002
TI  - The strength-duration relationship of monophasic waveforms with varying
      capacitance sizes in external defibrillation.
AB  - The shape of the shock waveform influences defibrillation efficacy. However, the
      optimal combination between capacitance size and truncation/tilt which can
      determine monophasic waveform's shape, has not been determined for external
      defibrillation. The purpose of this study was to assess the effects of varying
      capacitance and tilt on external defibrillation using exponential monophasic
      waveforms. In a pig model of external defibrillation (n = 10, 30 +/- 6 kg), nine
      exponential monophasic waveforms combining three capacitance values (30 microF,
      60 microF, and 120 microF) and three tilt values (55%, 75%, and 95%) were tested
      randomly. The energy and leading edge voltage at 50% defibrillation success (E50
      and V50) were used to evaluate defibrillation efficacy. E50 and V50 were
      determined by the Bayesian technique. The lowest stored E50 for the 30microF, 60
      microF, and 120 microF waveforms were 90 +/- 12 J (95% tilt), 106 +/- 45 J (55%
      tilt), and 107 +/- 52 J (75% tilt), respectively. The lowest V50 for the 30
      microF, 60 microF, and 120 microF waveforms were 2,439 +/- 166 V (95% tilt),
      1,849 +/- 375 V (55% tilt), and 1,301 +/- 322 V (75% tilt), respectively. The
      average current at external defibrillation threshold demonstrated a strength
      versus pulse duration relationship similar to that seen with pacing. Reducing
      capacitance has the same effect as truncating the waveform. The E50 is more
      sensitive to tilt values changes in larger capacitance waveforms. This study
      suggests that the optimal combination between capacitance and tilt may be 120
      microF and 55%-75% for external defibrillation.

PMID- 14675003
TI  - Clinical experience with an automatic threshold tracking algorithm study.
AB  - The automatic threshold tracking pacing system algorithm developed by St. Jude
      Medical, verifies ventricular capture beat by beat by recognizing the evoked
      response (ER) following each pacemaker stimulus. The present automatic threshold
      tracking function requires a bipolar ventricular lead with low polarization. The
      aim of this study was to evaluate a new algorithm developed to use with unipolar
      leads with different levels of polarization. An external pacemaker with the
      ability to sense intrinsic R waves and measure ER signals, as well as deliver
      stimulus, was used. An algorithm for detecting the true ER in a unipolar sensing
      configuration (tip-case) was developed. Based on the assumption that the true
      evoked R wave amplitude is independent of the stimulation amplitude, the
      algorithm calculates and subtracts the polarization present at any pacing
      stimulus from the measured ER. The resulting signal is analyzed to verify
      capture. This study comprises 35 patients of which 26 were new implants and 9 had
      chronic leads. The automatic threshold-tracking algorithm was calibrated for each
      patient and pacing was performed at different pulse amplitudes and pulse
      duration. Capture was verified for each paced beat. The recordings were stored
      for later comparison with the tape-recorded intracardiac heart signals. The new
      algorithm correctly verified capture or loss of capture for every single analyzed
      beat at the different pacing outputs in every individual patient. The results
      from this initial study suggests that the new ER detection principle will allow
      automatic threshold tracking to be used not only with low polarization bipolar
      leads but with most leads.

PMID- 14675004
TI  - Durability of repaired sensing leads equivalent to that of new leads in
      implantable cardioverter defibrillator patients with sensing abnormalities.
AB  - Breaks in the insulation portions of implantable cardioverter defibrillator (ICD)
      leads may cause nonphysiological sensing and subsequent inappropriate ICD
      therapy, and may also interfere with the sensing and pacing functions of the ICD.
      Previously, leads with insulation breaks have been replaced with new sensing
      leads. However, repair of leads, utilizing a commercially available patch kit may
      reduce the morbidity, hospital stay, and cost of lead replacement. The long-term
      durability of these repairs has not previously been reported and is the subject
      of this study. Patients undergoing ICD sensing lead repair or replacement
      constituted the study population. Patients were followed at 3 month intervals
      with an endpoint of new lead abnormalities necessitating repeat lead repair or
      replacement. Twenty-five patients underwent lead repair and 27 individuals
      underwent lead replacement for either preoperative nonphysiological sensing (n =
      25) or intraoperative evidence of insulation break (n = 27). There was no
      significant difference between the individuals undergoing lead repair or
      replacement in age (59 +/- 9 vs 60 +/- 12 years), mean left ventricular ejection
      fraction (40%+/- 18% vs 33%+/- 17%) or age of the lead being repaired or replaced
      (4.5 +/- 2.0 years vs 5.0 +/- 2.0 years). During follow-up of 44 +/- 23 months, 4
      of the repaired leads and 4 of the replaced leads developed new insulation breaks
      requiring surgical intervention (P = 0.43). In conclusion, in nearly 4 years of
      follow-up of patients with sensing lead insulation breaks, there was no
      difference is subsequent lead survival in those with lead repair compared to
      those with new sensing leads inserted. The strategy of lead repair, when
      technically feasible, should thus be considered in all patients with sensing
      abnormalities secondary to insulation breaks.

PMID- 14675005
TI  - Optimal pacing for symptomatic AV block: a comparison of VDD and DDD pacing.
AB  - VDD pacing provides the physiological benefits of atrioventricular synchronous
      pacing with the convenience of a single lead system, but is hampered by
      uncertainty regarding long-term atrial sensing and potential development of sinus
      node disease. To examine the long-term reliability and complication rates of VDD
      pacing, we compared the outcome of 112 consecutive patients (age 70 +/- 13 years,
      59% male) with symptomatic AV block who received a single pass bipolar VDD system
      to 80 patients (age 63 +/- 16 years, 70% male) who received DDD pacing for the
      same indication. All patients were judged to have intact sinus node function
      based on submitted ECGs and monitoring results at the time of implant. Implant
      time was reduced in VDD patients compared to DDD patients (63 +/- 20 vs 97 +/- 36
      minutes, P < 0.0001). Implant complications occurred in 5 (6%) DDD patients
      compared to 3 (3%) VDD patients (P = 0.15). The implant P wave was lower with VDD
      pacing compared to DDD patients (2.91 +/- 1.48 vs 4.0 +/- 1.7 mV, P < 0.0001),
      but remained stable during long-term follow-up in both groups. During 17.7 +/-
      10.0 months of follow-up in the VDD group, only 2 VDD patients were reprogrammed
      to VVIR mode, compared to 3 DDD patients. Physiological atrioventricular
      activation was maintained in 94%-99% of beats throughout the follow-up period in
      the VDD group. VDD pacing is an excellent strategy for treatment of patients with
      symptomatic AV block. The lower cost, high reliability, and abbreviated
      implantation time suggest that VDD pacing is a viable alternative to DDD pacing
      in patients with high-degree AV block and normal sinus node function.

PMID- 14675006
TI  - Factors determining ICD implantation in drug therapy patients after termination
      of antiarrythmics versus implantable defibrillators trial.
AB  - Because of a significant survival benefit in the defibrillator arm of the
      Antiarrhythmics versus Implantable Defibrillator (AVID) Trial, patients in the
      antiarrhythmic drug (AAD) arm were advised to undergo ICD implantation. Despite
      this recommendation, ICD implantation in AAD patients was variable, with a large
      number of patients not undergoing ICD implantation. Patients were grouped by
      those who had been on AAD < 1 year (n = 111) and those on AAD > 1 year (n = 223).
      Multiple clinical and socioeconomic factors were evaluated to identify those who
      might be associated with a decision to implant an ICD. The primary reason for
      patients not undergoing ICD implantation was collected, as well as reasons for a
      delayed implantation, occurring later than 3 months from study termination. Of
      111 patients on AAD for less than 1 year, 53 received an ICD within 3 months
      compared to 40/223 patients on AAD for more than 1 year (P < 0.001). Patient
      refusal was the most common reason to not implant an ICD in patients on drug < 1
      year; physician recommendation against implantation was the most common in
      patients on drug > 1 year. Multivariate analysis showed ICD recipients on AAD < 1
      year were more likely to be working and have a history of myocardial infarction
      (MI), while those on AAD > 1 year were more likely to be working, have a history
      of MI and ventricular fibrillation, and less likely to have experienced syncope,
      as compared to those who did not get an ICD. Having private insurance may have
      played a role in younger patients receiving an ICD.

PMID- 14675007
TI  - Conduction properties of the crista terminalis in patients with atrial flutter
      due to amiodarone therapy for atrial fibrillation.
AB  - Some patients with atrial fibrillation (AF) treated by antiarrhythmic drugs (AAD)
      can develop typical atrial flutter, but the mechanism is not clear. This study
      included 21 patients with AF. Group I (n = 7) had typical atrial flutter due to
      amiodarone therapy. Group II (n = 7) did not develop atrial flutter after
      amiodarone treatment. Group III (n = 7) did not receive AAD treatment. A 7 Fr, 20
      pole electrode catheter was placed along the CT identified by fluoroscopy and
      intracardiac echocardiography. After restoration of the sinus rhythm, decremental
      pacing near the CT was performed until 2 to 1 atrial capture. Complete transverse
      conduction block was defined as the appearance of double potentials with opposite
      activation sequence along the CT. Focal transverse conduction delay was defined
      as the appearance of double potentials at > or = 2 recording sites. Focal
      transverse conduction delay was observed during pacing at the cycle length of 693
      +/- 110 ms in group I, 360 +/- 97 ms in group II and 343 +/- 109 ms in group III
      (P = 0.001). Complete transverse conduction block was observed during pacing at
      the cycle length of 391 +/- 118 ms in group I and 231 +/- 23 ms in group II (P =
      0.001), but not in group III. In conclusion, focal transverse conduction delay in
      the CT was common in patients with AF. A predisposition to the line of the
      conduction block in the CT might contribute to the conversion of AF to typical
      atrial flutter due to amiodarone therapy.

PMID- 14675008
TI  - Induction of atrial fibrillation and nerve sprouting by prolonged left atrial
      pacing in dogs.
AB  - The authors hypothesized that rapid electrical stimulation can induce nerve
      sprouting in canine atria, and that LA pacing is more effective than RA pacing in
      inducing sustained AF. Chronic rapid (20 Hz) LA epicardial pacing was performed
      in six dogs. Sustained AF (>48 hours) was induced within 23 +/- 8 days, which was
      much faster than that with RA endocardial pacing using the same protocol (139 +/-
      84 days, P < 0.05). Nerves were identified by immunocytochemical techniques. In
      all dogs, growth-associated protein 43-positive (sprouting) nerve density was
      highest near the pacing site, and the rapid LA pacing resulted in differential
      nerve sprouting among the LA, left superior pulmonary vein (LSPV), interatrial
      septum (IAS), and RA (5521 +/- 1496, 3154 +/- 2355, 3953 +/- 1164, 1559 +/- 1077
      microm2/mm2, respectively, P = 0.0032). Tyrosine hydroxylase-positive
      (sympathetic) nerve density were not significantly different among groups (2726
      +/- 1165, 1586 +/- 558, 2156 +/- 1741, 1509 +/- 1242 microm2/mm2, respectively).
      The nerves were inhomogeneously distributed. LA epicardial pacing induced
      sustained AF much faster than RA endocardial pacing and rapid electrical
      stimulation can induce inhomogeneous nerve sprouting near the pacing site.

PMID- 14675009
TI  - Noncontact mapping of ventricular tachycardia in a closed-chest animal model of
      chronic myocardial infarction.
AB  - Treatment of ventricular tachyarrhythmias in the setting of chronic myocardial
      infarction requires accurate characterization of the arrhythmia substrate. New
      mapping technologies have been developed that facilitate identification and
      ablation of critical areas even in rapid, hemodynamically unstable ventricular
      tachycardia. A noncontact mapping system was used to analyze induced ventricular
      tachycardia in a closed-chest sheep model of chronic myocardial infarction.
      Twelve sheep were studied 96 +/- 10 days after experimental myocardial
      infarction. During programmed stimulation, 15 different ventricular tachycardias
      were induced in nine animals. Induced ventricular tachycardia had a mean cycle
      length of 190 +/- 30 ms. In 12 ventricular tachycardias, earliest endocardial
      activity was recorded from virtual electrodes, preceding the surface QRS onset by
      30 +/- 7 ms. Noncontact mapping identified diastolic activity in ten ventricular
      tachycardias. Diastolic potentials were recorded over a variable zone, spanning
      more than 30 mm. Timing of diastolic potentials varied from early to late
      diastole and could be traced back to the endocardial exit site. Entrainment with
      overdrive pacing was attempted in nine ventricular tachycardias, with concealed
      entrainment observed in seven. Abnormal endocardium in the area of chronic
      myocardial infarction identified by unipolar peak voltage mapping was confirmed
      by magnetic resonance imaging. These data suggest that induced ventricular
      tachycardia in the late phase of myocardial infarction in the sheep model is due
      to macroreentry involving the infarct borderzone. The combination of this animal
      model with noncontact mapping technology will allow testing of new strategies to
      cure and prevent ventricular tachycardia in the setting of chronic myocardial
      infarction.

PMID- 14675010
TI  - Electrical characteristics of a split cathodal pacing configuration.
AB  - Several electrical configurations can be used for biventricular pacing to achieve
      cardiac resynchronization. Commercially approved biventricular pacing systems
      stimulate the RV with an endocardial lead and the LV with a unipolar lead
      positioned in the cardiac venous circulation using the tip electrodes of both
      leads linked as a common cathode. The distribution of current with this parallel
      circuit, split cathodal configuration is dependent on the separate impedances of
      the two leads. A total of 19 patients with left bundle branch block and
      congestive heart failure underwent implantation of a cardiac venous lead and
      standard bipolar right atrial and RV pacing leads. Stimulation thresholds and
      impedances were measured for the RV and LV in five electrical configurations: (1)
      unipolar LV from the cardiac venous lead; (2) bipolar LV using the tip electrode
      in the cardiac vein as the cathode and the ring electrode of the RV lead as the
      anode; (3) bipolar RV from the RV lead; (4) unipolar split cathodal stimulation
      of the cardiac venous and RV leads; and (5) bipolar split cathodal stimulation of
      the cardiac venous and RV leads. Repeat measurements of RV and LV thresholds were
      made from the pulse generator at 1-year follow-up. The LV stimulation threshold
      increased from 0.7 +/- 0.5 V in the unipolar configuration to 1.0 +/- 0.8 V in
      the unipolar split cathodal configuration (P = 0.01) and from 1.0 +/- 0.7 V in
      the bipolar configuration to 1.3 +/- 0.9 V in the bipolar split cathodal
      configuration (P < 0.001). The RV stimulation threshold increased from 0.3 +/-
      0.2 V in the bipolar configuration to 0.5 +/- 0.2 V in the bipolar split cathodal
      configuration (P = 0.005). The bipolar impedance measured 874 +/- 299 Omega for
      the coronary venous lead, 705 +/- 152 for the RV lead, 442 +/- 87 in the split
      unipolar cathodal configuration, and 516 +/- 64 in the bipolar split cathodal
      configuration. At 1-year follow-up, the LV stimulation threshold was 1.8 +/- 1.6
      in the unipolar split cathodal configuration and 2.4 +/- 1.6 in the bipolar split
      cathodal configuration (P = 0.003). The RV stimulation threshold at 1 year was
      0.7 +/- 0.3 in the unipolar split cathodal configuration and 0.8 +/- 0.3 in the
      bipolar split cathodal configuration (P = 0.02). The split cathodal configuration
      significantly increases the apparent stimulation threshold for both the LV and
      the RV as compared with individual stimulation of either chamber alone.
      Programming to the bipolar split cathodal configuration further increases the
      apparent stimulation threshold. These observations support the development of
      pacing systems with separate LV and RV output circuits for resynchronization
      therapy.

PMID- 14675011
TI  - An approach to measure atrial and ventricular heart rate variability using
      pacemaker-mediated intracardiac electrograms.
AB  - Heart rate variability (HRV) measurements are usually performed from ventricular
      beat-to-beat intervals because of the difficulty to precisely locate the P wave
      fiducial point in surface ECG recordings. The aim of the study was to describe an
      approach to determine the atrial and ventricular HRV using pacemaker-mediated
      intracardiac electrograms. Twelve patients with the dual chamber pacemaker Logos
      were included. The atrial and ventricular intracardiac electrograms were
      transmitted with the high resolution telemetry channel of the pacemaker to an
      external recorder for 20 minutes while the patients were supine. During the
      measurements the patients were in sinus rhythm with intrinsic AV conduction.
      After computer assisted triggering of the atrial and ventricular events, the
      resultant intervals were used to calculate the standard deviation of all NN
      intervals (SDNN), the square root of the mean squared differences of successive
      NN intervals (RMSSD), and the percentage of successive interval differences >50
      ms (pNN50). The differences between atrial and ventricular HRV-Indexes were
      assessed for each patient with a cut-off point of 1%. Differences >1% were
      analyzed in detail. A total of 15,504 heart cycles were analyzed. A manual
      correction due to false or not triggered atrial or ventricular events was
      necessary in 0.9%. The overall difference between atrial and ventricular pNN50
      was-0.5%+/-2.1%and differences >1% were observed in 4 patients. The NN50 events
      occurred in the atrial as well as in the related ventricular interval in 84%.
      NN50 events occurred only in the atrium in 6% and only in the ventricle in 10%.
      The mean differences between atrial and ventricular SDNN and RMSSD were 0.4+/-2.1
      ms and-0.1+/-3.5 ms with intra-individual differences <1%. The present study
      described a new method and demonstrated its feasibility to determine atrial as
      well as ventricular HRV from pacemakermediated intracardiac electrograms. The
      differences for pNN50 indicate that ventricular HRV did not reflect the changes
      of sinus node activity in all patients.

PMID- 14675012
TI  - Safety and efficacy of a dual chamber implantable cardioverter defibrillator
      capable of slow ventricular tachycardia discrimination: a randomized study.
AB  - New developments in dual chamber implantable cardioverter defibrillators (ICD)
      have increased the specificity of therapy delivery. This study was performed to
      examine the performance of an algorithm, focusing on its ability to distinguish
      slow ventricular tachycardia (VT) from sinus rhythm or supraventricular
      tachyarrhythmias. The patient population included 77 men and 13 women, 63 +/- 11
      years old, treated with ICDs after episodes of spontaneous or inducible
      ventricular tachyarrhythmias. They were randomized to programming of the ICD to a
      lower limit of VT detection at 128 beats/min (group I, n = 44), versus 153
      beats/min II (group II, n = 46). The primary endpoint of the study consisted of
      comparing the specificity and sensitivity of the algorithm between the two groups
      of patients. Over a 10.1 +/- 3.5 months follow-up, 325 episodes were detected in
      the Tachy zone in group I, versus 106 in group II. The sensitivity and
      specificity of the algorithm in group I were 98.8% and 94.4%, respectively,
      versus 100% and 89% in group II (NS). A single episode of VT at a rate of 132
      beats/min was diagnosed as SVT in group I. The sensitivity and specificity of the
      algorithm for tachycardias <153 beats/min were 97.4% and 94.5%, respectively.
      Overall VT therapy efficacy was 100% in both groups. The performance of this
      algorithm in the slow VT zone supports the programming of a long Tachy detection
      interval to document slow events, and allows to treat slow VT, if necessary,
      without significant risk of inappropriate interventions for sinus tachycardia.

PMID- 14675013
TI  - Managing pacemaker safety alerts: experience with three successive models of a
      single manufacturer.
AB  - This report describes the experience of a large pacemaker center during three
      successive replacement operations due to safety alerts involving three models
      from the same manufacturer. Between March 1993 and May 1999, 210 patients were
      implanted with three DDD pacemaker models (Sorin Biomedica, Saluggia, Italy) that
      were subsequently subject to safety alerts. Pacemaker records were reviewed for
      complications related to device malfunction, and those secondary to the
      replacement procedure. Pacemaker malfunction was observed in 16.4% of units
      despite much lower estimates from the company (range 1-4%). With the exception of
      one, all units were replaced. Malfunctions were discovered in 7 of 20 pacemakers
      following an urgent call for follow-up issued as a result of the alert. Twenty
      units implanted as substitutes for those replaced following the first alert
      turned out to be subject to the third alert. Significant clinical consequences of
      malfunction occurred in 5.3% of patients including a near fatal event in one
      case, while complications related to the replacement procedure occurred in 8.3%
      of patients, including one fatality. On the issuance of a safety alert, failure
      rates in a particular center may be higher than published by the manufacturer,
      and should prompt action by the center to weigh local incidence of device failure
      against complications of replacement procedures. When device failure mechanism is
      not entirely clear, particularly in cases of successive model failures,
      replacement devices from a different manufacturer should be considered.

PMID- 14675014
TI  - Implantable cardioverter defibrillator events in patients with asymptomatic
      nonsustained ventricular tachycardia: is device implantation justified?
AB  - Primary prevention trials have demonstrated that patients with coronary disease,
      reduced left ventricular function, and nonsustained ventricular tachycardia
      (NSVT) have improved survival with implantable cardioverter defibrillator (ICD)
      therapy, presumably secondary to effective termination of life-threatening
      arrhythmias. However, stored intracardiac electrograms were not always available
      and specific arrhythmias leading to ICD therapy were not always known. We
      examined the occurrence of ICD events in 51 consecutive patients who match the
      described patient profile to determine the frequency of appropriate and
      inappropriate ICD therapy. ICD detections were noted in 18 (35%) patients during
      a median follow-up period of 13.1 months. Appropriate therapy for sustained
      ventricular tachycardia (VT)/ventricular fibrillation (VF) occurred in 11 (22%)
      patients, with appropriate shocks in 8 (16%) patients and appropriate
      antitachycardia pacing (ATP) in 4 (8%) patients. The time to first appropriate
      therapy occurred at a mean of 17 +/- 12 months (median 18 months, range 3-36
      months). Inappropriate therapy occurred in 5 (10%) patients with inappropriate
      shocks in 4 patients and inappropriate ATP in 2 patients. Inappropriate therapy
      was delivered for supraventricular arrhythmias (SVAs) in 4 patients and for T
      wave oversensing in 1 patient. The reason for shock therapy was unknown in 1
      patient (2%) due to ICD malfunction. The mean arrhythmia rate leading to
      appropriate therapy for VT/VF was 232 +/- 72 beats/min (range 181-400 beats/min),
      and the mean rate leading to inappropriate therapy for SVT was 168 +/- 10
      beats/min (range 160-180 beats/min). Patients with coronary disease and
      asymptomatic NSVT commonly receive appropriate defibrillator therapy. These
      results support the need for ICD implantation for primary prevention, with
      attention to careful programming of the detection rate to prevent inappropriate
      therapy.

PMID- 14675015
TI  - Differential diagnosis of slow/slow atrioventricular nodal reentrant tachycardia
      from atrioventricular reentrant tachycardia using concealed posteroseptal
      accessory pathway by 12-lead electrocardiography.
AB  - Slow pathways are used as both antegrade and retrograde conduction pathway in
      slow/slow atrioventricular nodal reentrant tachycardia (SS-AVNRT), and patients
      with SS-AVNRT have tachycardia ECGs mimicking atrioventricular reentrant
      tachycardia using concealed posteroseptal accessory pathway (PS-AVRT). Therefore,
      SS-AVNRT can be misdiagnosed as PS-AVRT, and the differential diagnosis is
      clinically important. Standard 12-lead ECGs during tachycardia were analyzed in
      patients with SS-AVNRT (n = 10) and PS-AVRT (n = 10). All these patients were
      diagnosed by electrophysiological study and underwent successful catheter
      ablation. Differences of the RP' intervals (dRP') between V1 and the inferior
      leads were evaluated. SS-AVNRT had significantly longer RP' intervals measured in
      V1 (167 +/- 25.2 vs 137 +/- 26.8 ms, SS-AVNRT vs PS-AVRT, respectively, P =
      0.02), longer dRP' between V1 and II (dRP'[V1-II], 37 +/- 14 vs 17 +/- 6.7 ms, P
      = 0.0007), longer dRP'[V1-III] (39 +/- 14 vs 17 +/- 9.9 ms, P = 0.0011), and
      longer dRP'[V1-aVF] (39 +/- 13 vs 20 +/- 9.5 ms, P = 0.0008). The following
      criteria were suggested for differential diagnosis of SS-AVNRT from PS-AVRT:
      dRP'[V1-II] >25 ms (sensitivity and specificity: 80% and 100%, respectively),
      dRP'[V1-III] >23 ms (90% and 90%), dRP'[V1-aVF] >30 ms (90% and 90%). Differences
      of the RP' intervals between V1 and the inferior leads in the tachycardia ECGs
      were useful for differential diagnosis of SS-AVNRT from PS-AVRT.

PMID- 14675016
TI  - Evaluation of the appropriateness of pacemaker mode selection in bradycardia
      pacing: how closely are the ACC/AHA guidelines followed?
AB  - Although guidelines for selection of the appropriate pacing mode have been
      published, little data is available on how closely these are followed in the
      clinical setting. All 738 patients (men 412, women 326; age 73.4 +/- 0.46 years;
      range 19-101 years) who underwent pacemaker implantation from 1996 to 2000 were
      reviewed to determine if the appropriate mode was selected based on the ACC/AHA
      guidelines with the data collected prospectively. Demographic, investigational,
      and implantation data including the presence of sinus disease and/or
      atrioventricular block, diagnosis, indication for pacing, ACC/AHA class
      indication for device therapy, recommended ACC/AHA mode, implanted mode, and
      reason for not using the recommended mode were entered into an SPSS data base. Of
      738 patients, 708 were cross-tabulated for a match to the guidelines of which 358
      (50.6%) had a mode selected that did not conform. The reasons were advanced
      physical disability (16%), physician choice without identifiable reason (21%),
      rate modulation selected without identifiable indication (16%), DDD implanted
      instead of VDD (25%), advanced age (9%), rare need for pacing (6%), a need for
      specific device features (5%), and unstable stimulation thresholds or difficult
      venous access (2%). In the treatment of bradyarrhythmias, deviation from the
      ACC/AHA indicated mode occurred in a substantial proportion of pacing system
      implantations. However, in many, the deviation appeared appropriate considering
      the patient's clinical status. Nevertheless, in a smaller proportion of patients
      the deviation appeared inappropriate requiring rectification. The two outstanding
      categories were: (1) elderly denied a dual chamber system with no clinical
      explanation and (2) selection of rate-modulated devices without any indication of
      chronotropic incompetence.

PMID- 14675017
TI  - The nature and frequency of postimplant surgical interventions: a realistic
      appraisal.
AB  - The purpose of this retrospective study was to investigate the nature and
      frequency of surgical reinterventions after primary pacemaker implantation in
      patients who survived at least 20-30 years. Eighty-five such patients were
      identified, 32 of whom had radioisotopic (nuclear) implants, and 53 lithium
      battery powered lithium units. Excluding reoperations within the first 3 months,
      patients with nuclear implants experienced about two reoperations in 25 years,
      while those with lithium experienced one every 8 years. The most frequent reasons
      for surgery were pulse generator replacements, lead revisions, and mode changes,
      particularly in the nuclear group. There were no premature device failures. This
      study allows us to make reasonable predictions to patients about the experience a
      pacemaker implantation, and reassures us about the reliability of the devices
      that were implanted in the past.

PMID- 14675018
TI  - Permanent pacing lead insertion through the cephalic vein using an hydrophilic
      guidewire.
AB  - The cephalic vein (CV) should be preferred to the subclavian vein for the
      insertion of permanent pacing leads because of better results. Unfortunately, the
      direct lead introduction using the standard CV cutdown is often unsuccessful.
      This study evaluated the efficacy and safety of a steerable hydrophilic guidewire
      (HGW) for lead insertion through the CV. An HGW was successfully introduced
      through the cephalic vein and into the subclavian vein. Over a 6-month period,
      115 consecutive patients underwent pacemaker implantation. In nine (7.8%)
      patients, the cephalic vein did not allow lead or guidewire introduction. The
      direct introduction of the leads through the CV was successful in 55 (51.9%) of
      106 patients. In 14 (12.2%) additional patients, a lead was inserted through the
      CV using a standard guidewire. The use of an HGW and of a split introducer
      allowed successful insertion of at least one lead in 35 (30.4%) additional
      patients. Overall, the HGW was successful in 35 (94.6%) of 37 of patients in
      which the technique was attempted. The CV approach was successful in 104 (90.4%)
      of 115 patients. In conclusion, the use of an HGW allows the insertion of a
      pacing lead through the CV in the great majority of patients in whom direct
      introduction and the use of a standard guidewire had failed. The technique
      significantly improves the success rate of the CV approach and may help to
      improve the acute and long-term results of permanent cardiac pacing.

PMID- 14675019
TI  - Reflections on the first catheter ablation of the atrioventricular junction.

PMID- 14675020
TI  - Quinolones: cardioprotective or cardiotoxic.
AB  - Quinolones block the rapid component of the delayed rectifier potassium current
      (Ik) in a dose dependent manner. This electrophysiological action translates into
      prolongation of the QT interval and may predispose to development of torsades de
      pointes. QT prolongation appears to be a class effect but there is a wide range
      of potency among class members. According to the available evidence, the
      fluoroquinolones that are currently on the market present a low risk of drug
      induced torsades de pointes, with a frequency of this adverse event occurring at
      a rate of approximately 0.2-2.7 per million prescriptions. The safest member of
      the class appears to be ciprofloxacin. ECG monitoring during initiation of
      quinolone treatment is indicated only in patients with conditions known to
      predispose to torsades or to those receiving concomitant medications that prolong
      the QT interval.

PMID- 14675021
TI  - Reproducible induction of atrioventricular nodal reentrant tachycardia with
      adenosine triphosphate.
AB  - A 29-year-old woman was referred for electrophysiological testing and
      radiofrequency ablation because of repeated episodes of palpitation of a 8-year
      duration. The 12-lead ECG during palpitations showed narrow QRS tachycardia at a
      rate of 160 beats/min. Dual AVN physiology according to electrophysiological
      criteria was not shown by single atrial extrastimulation and the tachycardia
      could not be induced. Slow/fast atrioventricular nodal reentrant tachycardia
      (AVNRT) was induced once by double atrial extrastimuli, but it was not
      reproducible. However, intravenous bolus injection of adenosine triphosphate
      (12.5 mg) during sinus rhythm led to reproducible initiation of slow/fast AVNRT.

PMID- 14675022
TI  - Upgrade of a chronic unipolar pacemaker to a biventricular pacemaker system.
AB  - With the development of cardiac resynchronization for patients with symptomatic
      heart failure and electrical dyssynchrony, there are patients with chronic
      pacemakers that meet the indications for biventricular pacing. Typically, this
      involves placement of the left ventricular lead with generator change to a dual
      chamber biventricular pacemaker, maintaining use of the right-sided leads. There
      are patients with older pacemaker systems that have unipolar leads with 5/6-mm
      pin connectors. These patients present challenges to upgrade that are separate
      from typical IS-1 system upgrades. Currently there are no pacemakers manufactured
      that accept the chronic 5/6-mm unipolar leads directly with the additional IS-1
      left heart lead. This report presents one such case in which a combination of
      adaptor and lead replacement resulted in upgrade to a biventricular system.

PMID- 14675023
TI  - Arrhythmogenic right ventricular cardiomyopathy (Naxos disease): report of a
      Turkish boy.
AB  - Naxos disease is a recessively inherited arrhythmogenic right ventricular
      cardiomyopathy in which the cardiac phenotype is associated with palmoplantar
      keratoderma and woolly hair. This disease is a heart muscle disorder causing life
      threatening ventricular arrhythmias, heart failure, and sudden cardiac death. The
      pathological hallmark of the disease is the progressive replacement of myocardial
      cells by fat and fibrous tissue. It appears in families descending from the
      Hellenic island of Naxos. We presented a 13-year-old Turkish boy with Naxos
      disease associated with ventricular tachycardia because of its rarity, and
      reviewed the literature.

PMID- 14675024
TI  - Acute pulmonary edema secondary to myocardial damage after electrical
      cardioversion.
AB  - Direct cardioversion used in the treatment of various cardiac arrhythmias is a
      highly effective and simple procedure with infrequent complications. An uncommon
      complication is the occurrence of pulmonary edema. This report describes a 68
      year-old woman with normal coronary arteries who experienced pulmonary edema
      following cardioversion secondary to myocardial injury demonstrated by ECG
      changes and elevation of troponin T.

PMID- 14675025
TI  - Treatment of pacemaker induced severe mitral regurgitation with biventricular
      pacing in two patients with a normal left ventricular ejection fraction.
AB  - This report describes two patients who developed severe mitral regurgitation and
      drug refractory congestive heart failure after implantation of a conventional
      pacemaker. Both patients had a normal left ventricular ejection fraction.
      Dramatic long-term improvement occurred following the institution of
      biventricular pacing that resulted in mild mitral regurgitation. The findings
      illustrate the benefit of cardiac resynchronization therapy in pacemaker induced
      left ventricular dyssynchrony causing severe mitral regurgitation and severe
      congestive heart failure in selected patients with a normal left ventricular
      ejection fraction.

PMID- 14675026
TI  - A safe and simple method for management of frozen pacemaker leads.
AB  - The traction of frozen leads from the generator header is difficult in some
      patients. This report describes the authors' experience with frozen leads in
      which the lead pins were removed by pushing with the tip of screwdriver from the
      hole created with a scalpel blade at the closed end of the generator header.

PMID- 14675027
TI  - Pseudotermination of atrioventricular nodal reentrant tachycardia related to
      isorhythmic atrioventricular dissociation.
AB  - Unusual manifestations of the mode of termination were observed in a patient with
      atrioventricular nodal reentrant tachycardia (AVNRT). After administration of
      verapamil during AVNRT, isorhythmic atrioventricular dissociation occurred
      without termination of the tachycardia. The sinus rate was slightly faster than
      that of the AVNRT, leading to the P wave preceding the QRS complex with a normal
      PR interval (e.g., pseudotermination). This phenomenon emphasizes the importance
      of continuous monitoring during an attempt to terminate AVNRT.

PMID- 14675028
TI  - Antiarrhythmic drugs: past, present, and future.

PMID- 14675029
TI  - Gender differences in ventricular repolarization: terminal T wave interval was
      shorter in women than men.

PMID- 14675031
TI  - The phosphatonin pathway: new insights in phosphate homeostasis.
AB  - Serum phosphate concentrations are maintained within a defined range by processes
      that regulate the intestinal absorption and renal excretion of inorganic
      phosphate. The hormones currently believed to influence these processes are
      parathyroid hormone (PTH) and the active metabolite of vitamin D, 1alpha,25
      dihydroxyvitamin D (1alpha,25(OH)2D). A new class of phosphate-regulating
      factors, collectively known as the phosphatonins, have been shown to be
      associated with the hypophosphatemic diseases, tumor-induced osteomalacia (TIO),
      X-linked hypophosphatemic rickets (XLH), and autosomal-dominant hypophosphatemic
      rickets (ADHR). These factors, which include fibroblast growth factor 23 (FGF23)
      and secreted frizzled-related protein 4 (FRP4), decrease extracellular fluid
      phosphate concentrations by directly reducing renal phosphate reabsorption and by
      suppressing 1alpha,25(OH)2D formation through the inhibition of 25-hydroxyvitamin
      D 1alpha-hydroxylase. The role of these substances under normal or pathologic
      conditions is not yet clear. For example, it is unknown whether any of the
      phosphatonins are directly responsible for the decreased concentrations of
      1alpha,25(OH)2D observed in chronic and end-stage kidney disease or whether they
      are induced in an attempt to correct the hyperphosphatemia seen in late stages of
      chronic renal failure. Future experiments should clarify their physiologic and
      pathologic roles in phosphate metabolism.

PMID- 14675032
TI  - Platelet-derived growth factor plays a critical role to convert bone marrow cells
      into glomerular mesangial-like cells.
AB  - BACKGROUND: Despite increasing interest in bone marrow-derived stem cells, little
      is known about critical factors that determine their fates both in vitro and in
      vivo. Recently, we have reported that bone marrow is a reservoir for glomerular
      mesangial cells in rats. To find a key factor responsible for the differentiation
      of bone marrow-derived cells into mesangial cells, we established a new culture
      system of rat bone marrow, which is based on serial replating and differential
      attachment to collagen types I and IV. METHODS: Bone marrow cells that did not
      adhere to collagen type I within 24 hours were transferred to collagen type IV
      coated dishes. Then, the cells attached to collagen type IV in the following 24
      hours were maintained in the presence of 2% horse serum, 200 ng/mL of platelet
      derived growth factor (PDGF)-BB, and 1 micromol/L of all-trans retinoic acid. In
      vivo effect of PDGF-B was also examined by introducing human PDGF-B gene into
      glomeruli. RESULTS: After cultivation under the above condition for 7 days,
      approximately 14% of cells expressed Thy-1 and desmin, both of which are markers
      for rat mesangial cells. Thy-1++/desmin+ cells were stellate-shaped, and
      contracted in response to angiotensin II. When human PDGF-B gene was
      overexpressed in the glomeruli of chimeric rats whose bone marrow was
      transplanted from enhanced green florescent protein (EGFP) transgenic rats, the
      number of EGFP+ mesangial cells increased. This effect was canceled by prior
      introduction of a neutralizing molecule that is composed of PDGF receptor-beta
      ligand binding site and IgG-Fc. CONCLUSION: These results indicate that PDGF-B
      plays a critical role to direct bone marrow-derived cells toward mesangial-like
      cells both in vitro and in vivo.

PMID- 14675033
TI  - A new mutation (intron 9 +1 G>T) in the SLC12A3 gene is linked to Gitelman
      syndrome in Gypsies.
AB  - BACKGROUND: Gitel syndrome is an inherited tubular disorder characterized by
      metabolic alkalosis, hypokalemia, and hypomagnesemia of renal origin and
      hypocalciuria. The majority of patients with Gitelman syndrome carry inactivating
      mutations in the SLC12A3 gene encoding the sodium-chloride cotransporter located
      in the distal convoluted tubule. The purpose of this study was to investigate the
      underlying mutation in Gitelman syndrome patients of Gypsy race from different
      geographic origin. METHODS: Twenty Gypsy patients with clinical and biochemical
      features of Gitelman syndrome were investigated by mutational analysis. The
      patients belonged to 12 unrelated Gypsy families living in four different
      European countries. The parents and unaffected siblings of each patient, as well
      as the DNA of a population of 200 healthy control patients, were also analyzed.
      RESULTS: All patients were homozygous for the same splice site mutation, guanine
      to thymine in the first position of intron 9 of SLC12A3 gene. This mutation was
      not found in the control population. Parents were heterozygous for the mutation.
      Despite sharing a common mutation, the clinical manifestations of the syndrome in
      the patients varied from lack of symptoms in six children to severe growth
      retardation in four. CONCLUSION: Demonstration of a novel point mutation within
      the SLC12A3 gene in our cohort of Gypsy families with Gitelman syndrome is highly
      suggestive of a founder effect. This finding will facilitate the identification
      of the genetic defect in further cases of Gitelman syndrome among the Gypsy
      population. Our study represents the largest series ever published of patients
      with Gitelman syndrome having the same underlying mutation, and supports the lack
      of correlation between genotype and clinical phenotype in this disease.

PMID- 14675034
TI  - Activation of a local tissue angiotensin system in podocytes by mechanical
      strain.
AB  - BACKGROUND: Glomerular capillary hypertension, a common denominator in various
      forms of progressive glomerular disease, results in mechanical distention of the
      capillary tuft, and subsequent injury of the overlying podocyte layer. The
      mechanisms by which elevated intraglomerular pressure is translated into a
      maladaptive podocyte response remain poorly understood. Angiotensin II plays a
      central role in the pathogenesis of chronic renal injury, largely through its
      actions on the subtype 1 receptor. Accordingly, we have tested the hypothesis
      that mechanical strain up-regulates local angiotensin II in podocytes, thereby
      resulting in a progressive reduction in podocyte number. METHODS: Conditionally
      immortalized mouse podocytes were subjected to cyclical stretch of 10% amplitude.
      Nonstretched podocytes served as controls. Angiotensin II levels were measured in
      whole cell lysate by competitive enzyme-linked immunosorbent assay (ELISA).
      Expression of angiotensin II receptors (AT1R, AT2R) was measured by quantitative
      polymerase chain reaction (PCR) and Western blot analysis. Apoptosis was measured
      by Hoechst staining. Immunostaining for AT1R was performed in tissue sections
      from rats with 5/6 remnant kidney disease, a model of glomerular hypertension.
      RESULTS: Mechanical strain increased angiotensin II production in podocytes at
      24, 48, and 72 hours (P < 0.05 vs. nonstretched controls). Stretching podocytes
      resulted in a fivefold increase in AT1R mRNA expression at 24 hours and a twofold
      increase in protein levels vs. controls (P < 0.05), and also an increase in
      transforming growth hormone-beta (TGF-beta) mRNA expression. AT1R staining was
      increased in a podocyte distribution in the 5/6 remnant kidney, consistent with
      our in vitro findings. Mechanical strain resulted in a 2.5-fold increase in
      apoptosis (P < 0.001 vs. nonstretched controls) in an angiotensin II-dependent
      fashion. CONCLUSION: Mechanical strain leads to up-regulation of the AT1R and
      increased angiotensin II production in conditionally immortalized podocytes. The
      resulting activation of a local tissue angiotensin system leads to an increase in
      podocyte apoptosis, mainly in an AT1R-mediated fashion.

PMID- 14675035
TI  - Guanylin and uroguanylin induce natriuresis in mice lacking guanylyl cyclase-C
      receptor.
AB  - BACKGROUND: Guanylin (GN) and uroguanylin (UGN) are intestinally derived peptide
      hormones that are similar in structure and activity to the diarrhea-causing
      Escherichia coli heat-stable enterotoxins (STa). These secretagogues have been
      shown to affect fluid, Na+, K+, and Cl- transport in both the intestine and
      kidney, presumably by intracellular cyclic guanosine monophosphate (cGMP)
      dependent signal transduction. However, the in vivo consequences of GN, UGN, and
      STa on renal function and their mechanism of action have yet to be rigorously
      tested. METHODS: We hypothesized that intravenous administration of GN, UGN, or
      STa would cause an increase in natriuresis in wild-type mice via cGMP and
      guanylyl cyclase-C (GC-C, Gucy2c), the only known receptor for these peptide
      hormones, and that the peptide-induced natriuresis would be blunted in
      genetically altered mice devoid of GC-C receptors (GC-C(-/-) null). RESULTS: In
      wild-type mice using a modified renal clearance model, GN, UGN, and STa elicited
      significant natriuresis, kaliuresis, and diuresis as well as increased urinary
      cGMP levels in a time- and dose-dependent fashion. Absolute and fractional
      urinary sodium excretion levels were greatest approximately 40 minutes following
      a bolus infusion with pharmacologic doses of these peptides. Unexpectedly, GC-C(
      /-) null mice also responded to the GN peptides similarly to that observed in
      wild-type mice. Glomerular filtration rate (GFR), blood pressure, and plasma cGMP
      in the mice (wild-type or GC-C(-/-) null) did not significantly vary between the
      vehicle- and peptide-treatment groups. The effects of UGN may also influence long
      term renal function due to down-regulation of the Na+/K+ ATPase gamma-subunit and
      the Cl- channel ClC-K2 by 60% and 75%, respectively, as assessed by differential
      display polymerase chain reaction (PCR) (DD-PCR) and Northern blot analysis of
      kidney mRNA from mice treated with UGN. CONCLUSION: GN, UGN, and STa act on the
      mouse kidney, in part, through a cGMP-dependent, GC-C-independent mechanism,
      causing significant natriuresis by renal tubular processes. UGN may have further
      long-term effects on the kidney by altering the expression of such transport
      associated proteins as Na+/K+ ATPase and ClC-K2.

PMID- 14675036
TI  - Acute endotoxemia in rats induces down-regulation of V2 vasopressin receptors and
      aquaporin-2 content in the kidney medulla.
AB  - BACKGROUND: Endotoxemia can lead to fluid metabolism alterations despite
      unchanged or elevated plasma vasopressin (VP) levels, suggesting a refractoriness
      of the kidney to the effect of the peptide. To test this hypothesis, we examined
      the effect of lipopolysaccharide (LPS) injection on the expression of V2
      receptors and aquaporin-2 in the kidney. METHODS: Plasma VP and urine osmolality,
      and binding of [3H]VP to kidney membranes, Western blot, and immunohistochemical
      analysis of aquaporin-2, in situ hybridization for V2 VP receptors and cytokines
      mRNAs were measured in the kidney 3 to 24 hours after LPS injection, 250
      microg/100 g, intraperitoneally. RESULTS: LPS injection caused prolonged
      decreases in urine osmolality (up to 24 hours) without significant changes in
      plasma levels of sodium or VP. This was associated with marked decreases in V2 VP
      receptor mRNA and VP receptor number in the kidney, which were evident for up to
      12 hours after LPS injection. Aquaporin-2 in kidney inner medulla was also
      reduced by about 50%. LPS induced interleukin (IL)-1beta in the kidney medulla by
      3 hours, reached maximum at 6 hours, and started to decline by 12 hours, while it
      increased IL-6 mRNA significantly only at 3 hours. Interleukin mRNA expression
      was absent in kidneys of control rats. In vitro incubation of kidney medulla
      slices with IL-1beta reduced VP binding. CONCLUSION: The inflammatory response to
      acute endotoxemia down regulates V2 VP receptors and aquaporin-2 of the kidney
      inner medulla resulting in prolonged impairment of the renal capacity to
      concentrate urine.

PMID- 14675037
TI  - Treatment with anti-TGF-beta antibody ameliorates chronic progressive nephritis
      by inhibiting Smad/TGF-beta signaling.
AB  - BACKGROUND: Although short-term treatment with anti-transforming growth factor
      beta (TGF-beta) antibody (alphaT) has been shown to prevent early glomerular
      lesions, its long-term effects and molecular mechanisms, including intracellular
      signaling, remain poorly understood. We examined whether alphaT treatment induces
      prevention of renal insufficiency and fibrosis, and affects the TGF-beta/Smad
      signaling pathway in rats with chronic progressive anti-thymocyte serum (ATS)
      nephritis induced by repeated ATS injections on days 0 and 7. METHODS: Nephritic
      and non-nephritic rats were treated with either alphaT or control immunoglobulin
      (Ig)G twice weekly for 4 weeks from days 7 to 35 (each group, N= 21). Renal
      lesions and cortical expression of TGF-beta1, TGF-beta2, TGF-beta3, type II TGF
      beta receptor (TbetaRII), Smads, type I collagen, and plasminogen activator
      inhibitor-1 were examined by immunohistochemistry, Western blot, and/or real-time
      reverse transcription polymerase chain reaction (RT-PCR). The binding of Smad3 in
      renal cortical cell nuclei to the Smad-binding element (SBE) was investigated by
      the electrophoretic mobility shift assay. RESULTS: Nephritic rats developed heavy
      proteinuria, renal insufficiency, and increased extracellular matrix deposition
      resulting in renal fibrosis. Cortical expression levels of TGF-beta1, TGF-beta2,
      TbetaRII, and Smad2, but not TGF-beta3, Smad3, and Smad4 were increased.
      Expression and preferential localization of phosphorylated Smad2/3 in the
      glomerular and tubular cell nuclei, and Smad3-SBE complex-forming activity were
      also increased. Four-week alphaT treatment resulted in marked amelioration of
      chronic progressive ATS nephritis at 8 weeks. CONCLUSION: In chronic progressive
      ATS nephritis, the TGF-beta/Smad signaling was up-regulated. TGF-beta blockade by
      alphaT suppressed the progression of renal scarring, at least in part, via
      inhibition of activated TGF-beta/Smad signaling.

PMID- 14675038
TI  - Proteinase 3 sidesteps caspases and cleaves p21(Waf1/Cip1/Sdi1) to induce
      endothelial cell apoptosis.
AB  - BACKGROUND: Emerging data raise possibilities of a complex and specific biologic
      role for leukocyte-derived proteases in substrate processing and in signaling
      pathways. Neutrophil proteinase 3 (PR3) is a caspase-like protease that enters
      endothelial cells, cleaves nuclear factor-kappaB (NF-kappaB), and induces
      sustained JNK activation, implying that the major cell cycle inhibitor p21 may be
      inactivated. Cleavage of p21 by caspase-3 is reported to be required for
      endothelial cell apoptosis. We hypothesized that PR3 may target p21. METHODS:
      Human umbilical vein endothelial cells (HUVEC) were treated with or without PR3
      (5 microg/mL) from 0 hours or up to 8 hours, and analyzed for changes in cell
      cycle control proteins by immunoblotting, immunofluorescence and flow cytometry.
      RESULTS: PR3 exposure resulted in cleavage of p21 between Thr80 and Gly81, loss
      of nuclear p21 by cytoplasmic sequestration and depletion of p21 from
      cyclin/cyclin-dependent kinase (CDK) complexes. Examination of cyclins D and E,
      p53, Rb, and p27 revealed a largely nonproliferative expression profile. Cells
      arrested in G1 were more susceptible to PR3 effects. We examined inflamed human
      colonic tissue and found a fragment similar in size to that generated by PR3 in
      HUVEC. Granzyme B, a T-cell homologue of PR3 that cleaves caspase substrates,
      also cleaves p21 between Asp62 and Phe63. A reported substrate of granzyme B and
      caspases, Bid, is cleaved by PR3 signifying commonality of substrates among these
      proteases. CONCLUSION: A theme is developing that the granulocyte protease, PR3,
      is an exogenous caspase-like molecule that can sidestep intracellular caspase
      functions at sites of inflammation.

PMID- 14675039
TI  - Proliferative glomerulonephritis with monoclonal IgG deposits: a distinct entity
      mimicking immune-complex glomerulonephritis.
AB  - BACKGROUND: Renal disease related to the deposition of monoclonal immunoglobulins
      containing both heavy and light chains can occur in type 1 cryoglobulinemia,
      Randall type light and heavy chain deposition disease (LHCDD), and immunotactoid
      glomerulonephritis. We report a novel phenotype of glomerular injury that does
      not conform to any of the previously described patterns of glomerular involvement
      by monoclonal gammopathy. METHODS: Ten cases of unclassifiable proliferative
      glomerulonephritis manifesting glomerular monoclonal immunoglobulin G (IgG)
      deposits were identified retrospectively from the archives of the Renal Pathology
      Laboratory of Columbia University over the past 3 years (biopsy incidence 0.21%).
      RESULTS: The monoclonal immunoglobulins formed granular electron dense deposits
      in mesangial, subendothelial, and subepithelial sites, mimicking ordinary immune
      complex-mediated glomerulonephritis and producing a diffuse endocapillary
      proliferative or membranoproliferative glomerulonephritis. However, by
      immunofluorescence, the deposits were monoclonal, staining for a single light
      chain isotype and a single gamma subclass (including two IgG1kappa, one
      IgG1lambda, one IgG2lambda, four IgG3kappa, and one IgG3lambda). All cases
      stained for the three constant domains of the gamma heavy chain (CH1, CH2, and
      CH3), suggesting deposition of a nondeleted immunoglobulin molecule. Tissue
      fixation of complement was observed in 90% of cases, and 40% of patients had
      hypocomplementemia. Clinical presentations included renal insufficiency in 80%
      (mean serum creatinine 2.8 mg/dL, range 0.9 to 8.0), proteinuria in 100% (mean
      urine protein 5.8 g/day; range 1.9 to 13.0), nephrotic syndrome in 44%, and
      microhematuria in 60%. A monoclonal serum protein with the same heavy and light
      chain isotype as that of the glomerular deposits was identified in 50% of cases
      (including three IgGkappa and two IgGlambda); however, no patient had clinical or
      laboratory features of type 1 cryoglobulinemia. No patient had overt myeloma or
      lymphoma at presentation or over the course of follow-up (mean 12 months).
      CONCLUSION: Glomerular deposition of monoclonal IgG can produce a proliferative
      glomerulonephritis that mimics immune-complex glomerulonephritis by light and
      electron microscopy. Proper recognition of this entity requires confirmation of
      monoclonality by staining for the gamma heavy chain subclasses.

PMID- 14675040
TI  - Improvement of extraction and processing of RNA from renal biopsies.
AB  - BACKGROUND: Assessment of mRNA levels has the potential to predict renal outcome.
      The objective of this study was to optimize several steps in the protocol for
      obtaining cDNA from routine clinical kidney biopsy material. METHODS: RNA
      integrity was compared between different methods for extraction of RNA, synthesis
      of cDNA, and storage of renal tissue. Hereby, RNAlater, an RNA-preserving
      compound, was tested for implementation in a protocol for renal biopsies that
      combines routine histology and RNA expression studies. Gel electrophoresis and
      real-time polymerase chain reactions (PCR) were outcome parameters for assessment
      of RNA integrity. RESULTS: The Trizol method rendered higher RNA yields from
      fresh renal tissue than the NP40 method and RNeasy spin columns. RNA yields were
      not affected when renal tissue was stored at -70 degrees C for up to 2 months in
      phosphate-buffered saline (PBS). cDNA levels obtained using avian myeloblastosis
      virus (AMV) reverse transcriptase (RT) were at least twice as high as those
      obtained with Sensiscript and Superscript RT. RNAlater maintained RNA integrity
      in whole renal cortex stored at 4 degrees C for up to 3 months. Dissection of
      small biopsies in RNAlater rendered similar RNA yields in comparison with
      dissection in PBS, but the yield of glomeruli from the cortices was 50% lower (P
      < 0.005). Integrity of RNAlater-treated tissue, evaluated by light microscopy and
      immunofluorescence, was diminished. CONCLUSION: This study shows optimization of
      several steps in the protocol for extraction and handling of RNA in renal
      cortical tissue. RNA extraction and cDNA synthesis can be optimized by the use of
      the Trizol method and AMV RT, respectively. RNAlater is beneficial for preserving
      RNA integrity in whole renal cortex during storage and processing, but is not
      suitable for implementation in routine diagnostic histologic stainings combined
      with RNA expression studies in dissected biopsy material.

PMID- 14675041
TI  - Divergent effects of low versus high dose anti-TGF-beta antibody in puromycin
      aminonucleoside nephropathy in rats.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) modulates
      immune/inflammatory cells, promotes extracellular matrix (ECM) accumulation, and
      is increased in fibrotic organs. Here we report the effects of administering a
      puromycin aminonucleoside nephropathy (PAN)-specific TGF-beta neutralizing
      antibody on glomerulosclerosis in vivo. METHODS: Adult male Sprague-Dawley rats
      underwent uninephrectomy (Nx) followed by intraperitoneal PAN at weeks 2, 6, 7
      and 8. Rats were treated with either high (5 mg/kg body weight) (N= 9) or low
      (0.5 mg/kg body weight) (N= 7) dose TGF-beta antibody intraperitoneally three
      times weekly until sacrifice at week 10. A PAN untreated control group (N= 7) was
      dosed with an isotype specific, null antibody. The nephrectomy samples were
      studied as normal kidney control (NL) (N= 5). Rats undergoing left kidney Nx (N=
      5) only were also included as age-matched control. Renal function and morphology
      were assessed, and molecular studies performed. RESULTS: Systolic blood pressure
      was increased in parallel over time in all groups (at 10 weeks, control 137 +/-
      10 mm Hg; high 129 +/- 4 mm Hg; low 137 +/- 3 mm Hg) (P= NS). Both TGF-beta
      antibody treatments decreased renal cortex mRNA expressions similarly for TGF
      beta1, TGF-beta2, and collagen III (TGF-beta1, control 0.36 +/- 0.02 mm Hg; high
      0.19 +/- 0.01 mm Hg; low 0.19 +/- 0.02 mm Hg; P < 0.01 low and high vs. control;
      TGF-beta2, control 0.38 +/- 0.03 mm Hg; high 0.19 +/- 0.02 mm Hg; low 0.20 +/-
      0.03 mm Hg; P < 0.01 low and high vs. control; and collagen III, control 0.33 +/-
      0.01 mm Hg; high 0.14 +/- 0.01 mm Hg; low 0.19 +/- 0.01 mm Hg; P < 0.01 low and
      high vs. control; P < 0.05 low vs. high, data expressed as mRNA normalized
      density units vs. 18S RNA). However, only low dose TGF-beta antibody improved
      renal function and sclerosis measured by serum creatinine and creatinine
      clearance (serum creatinine, control 2.3 +/- 0.5 mg/dL; high 2.5 +/- 0.5 mg/dL;
      low 0.8 +/- 0.1 mg/dL; P < 0.05 low vs. control and high; creatinine clearance,
      control 0.44 +/- 0.11 mL/min; high 0.70 +/- 0.26 mL/min; low 1.34 +/- 0.30
      mL/min; P < 0.05 low vs. control, P= NS vs. high). In parallel, sclerosis index
      (0 to 4+ scale) was improved in low dose (control 2.67 +/- 0.27; high 2.37 +/-
      0.30; low 1.78 +/- 0.24; P < 0.05 low vs. control). This improved function and
      structure was linked to decreased glomerular infiltrating macrophages (0 to 4+
      score, control 2.3 +/- 0.2; high 1.8 +/- 0.4; low 0.8 +/- 0.1; P < 0.01 low vs.
      control; P < 0.05 low vs. high; P= NS high vs. control). Further, plasminogen
      activator inhibitor-1 (PAI-1) mRNA expression in renal cortex was attenuated
      after low dose TGF-beta antibody treatment compared to control and high dose
      group (PAI-1/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratio, NL 0.18
      +/- 0.003; control 0.45 +/- 0.03; high 0.40 +/- 0.04; low 0.23 +/- 0.01; P < 0.05
      low vs. control and high). Matrix metalloproteinase-9 (MMP-9) activity was
      maintained at higher levels in kidneys of the low dose TGF-beta antibody-treated
      group. CONCLUSION: These results show an in vivo dose-response with an agent that
      blocks the biologic activity of TGF-beta. Higher dose of TGF-beta antibody was
      without beneficial effect, suggesting that TGF-beta-mediated effects on PAI-1 and
      macrophage influx are bimodal and closely regulated. Given that both antibody
      doses reduced the expression of TGF-beta isoforms and collagen III production,
      but only low dose ameliorated histologic sclerosis, it appears that pharmacologic
      effects of anti-TGF-beta antibody on matrix synthesis and degradation are not
      equivalent.

PMID- 14675042
TI  - Macrophages in mouse type 2 diabetic nephropathy: correlation with diabetic state
      and progressive renal injury.
AB  - BACKGROUND: Macrophage-mediated renal injury has been implicated in progressive
      forms of glomerulonephritis; however, a role for macrophages in type 2 diabetic
      nephropathy, the major cause of end-stage renal failure, has not been
      established. Therefore, we examined whether macrophages may promote the
      progression of type 2 diabetic nephropathy in db/db mice. METHODS: The incidence
      of renal injury was examined in db/db mice with varying blood sugar and lipid
      levels at 8 months of age. The association of renal injury with the accumulation
      of kidney macrophages was analyzed in normal db/+ and diabetic db/db mice at 2,
      4, 6, and 8 months of age. RESULTS: In db/db mice, albuminuria and increased
      plasma creatinine correlated with elevated blood glucose and hemoglobin A1c
      (HbA1c) levels but not with obesity or hyperlipidemia. Progressive diabetic
      nephropathy in db/db mice was associated with increased kidney macrophages.
      Macrophage accumulation and macrophage activation in db/db mice correlated with
      hyperglycemia, HbA1c levels, albuminuria, elevated plasma creatinine, glomerular
      and tubular damage, renal fibrosis, and kidney expression of macrophage
      chemokines [monocyte chemoattractant protein-1 (MCP-1), osteopontin, migration
      inhibitory factor (MIF), monocyte-colony-stimulating factor (M-CSF)]. The accrual
      and activation of glomerular macrophages also correlated with increased
      glomerular IgG and C3 deposition, which was itself dependent on hyperglycemia.
      CONCLUSION: Kidney macrophage accumulation is associated with the progression of
      type 2 diabetic nephropathy in db/db mice. Macrophage accumulation and activation
      in diabetic db/db kidneys is associated with prolonged hyperglycemia, glomerular
      immune complex deposition, and increased kidney chemokine production, and raises
      the possibility of specific therapies for targeting macrophage-mediated injury in
      diabetic nephropathy.

PMID- 14675043
TI  - Effects of complement factor D deficiency on the renal disease of MRL/lpr mice.
AB  - BACKGROUND: The alternative complement pathway (AP) is activated in individuals
      with lupus nephritis and in murine models of systemic lupus erythematosus,
      including MRL/lpr mice. A previous study from our laboratory evaluated the
      development of renal disease in MRL/lpr mice genetically deficient in factor B
      (Bf-/-), a protein necessary for AP activation. MRL/lpr Bf-/- mice developed less
      renal disease and had improved survival; however, these mice were also a
      different major histocompatibility complex (MHC) haplotype (H-2b) than their wild
      type littermates (H-2k) due to the gene for Bf being located in the MHC gene
      complex. We undertook the current study to determine if the decreased renal
      disease in MRL/lpr Bf-/- mice was due to the lack of AP activation or the H-2b
      haplotype by studying the effects of factor D (Df) deficiency, a critical protein
      for AP activation, on disease development in MRL/lpr mice. METHODS: Df-deficient
      mice were backcrossed with MRL/lpr mice for four to nine generations. MRL/lpr H
      2k Df-/-, Df+/-, and Df+/+ littermates were evaluated for disease development.
      Lack of AP activation in MRL/lpr Df-/- mice was determined by the zymosan assay.
      Serum creatinine levels were measured using a creatinine kit. Proteinuria and
      autoantibody levels were determined by enzyme-linked immunosorbent assay (ELISA).
      Sections from one kidney were stained with fluorescein isothiocyanate (FITC)
      alpha-murine C3 or alpha-murine IgG to detect C3 and IgG deposition. The
      remaining kidney was cut in half with one half fixed, sectioned, and stained with
      hematoxylin and eosin and periodic acid-Schiff (PAS) to evaluate pathology and
      another half fixed in glutaraldehyde and examined via electron microscopy.
      RESULTS: MRL/lpr Df-/- mice had similar glomerular IgG deposition, proteinuria
      and autoantibody levels, as Df+/+ and Df+/- littermates. However, glomerular C3
      deposition, serum creatinine levels, and pathologic renal disease were
      significantly reduced in Df-/- mice. Despite the lack of renal disease in Df-/-
      mice, life span was not impacted by factor D deficiency. CONCLUSION: The absence
      of Df and AP activation is protective against the development of proliferative
      renal disease in MRL/lpr mice suggesting the similar effect of Bf deficiency in
      MRL/lpr mice was also due to the lack of AP activation.

PMID- 14675044
TI  - Hydrogen peroxide mediates FK506-induced cytotoxicity in renal cells.
AB  - BACKGROUND: The nephrotoxicity induced by immunosuppressant FK506 remains a
      serious clinical problem, and the underlying mechanism has not been completely
      understood. The present study was undertaken to determine the role of hydrogen
      peroxide in FK506-mediated cytotoxicity in a porcine renal proximal tubular cell
      line, LLC-PK1 cells, and human embryonic kidney (HEK293) cells. METHODS:
      Cytotoxicity was estimated by crystal violet and lactate dehydrogenase release
      assays. The activity of reactive oxygen species (ROS) was detected by flow
      cytometry. FK506-induced cell death was examined in the presence of the hydrogen
      peroxide scavenger, catalase, or a scavenger of hydroxyl radicals, sodium
      benzoate. As a control, FK506-induced cell death was also measured in the
      presence of superoxide anion inhibitor, 4,5-dihydroxy-1,2-benzene disulfonic acid
      (Tiron), TEMPO, or overexpressed human manganese superoxide dismutase (MnSOD).
      Catalase was also used in tumor necrosis factor-alpha (TNF-alpha)-induced cell
      injury to determine whether the enzyme specifically protected cells against FK506
      mediated cytotoxicity. RESULTS: FK506 induced cell death in a dose-dependent
      manner and coincided with a dose-dependent increase in ROS activity. Abrogation
      of FK506-mediated ROS by catalase and N-acetylcysteine blunted FK506-induced cell
      death. Furthermore, overexpression of catalase, sodium benzoate, and deferoxamine
      inhibited the cytotoxic effect of FK506. In contrast, Tiron, TEMPO, or
      overexpression of human MnSOD failed to show cytoprotection. In fact, TEMPO or
      expression of MnSOD enhanced the effect of FK506. Catalase did not significantly
      affect TNF-alpha-induced cell injury. CONCLUSION: Catalase is uniquely required
      in cellular protection against FK506 cytotoxicity, which suggests an important
      role for hydrogen peroxide in the cellular actions of FK506.

PMID- 14675045
TI  - Pathologic findings of initial biopsies reflect the outcomes of membranous
      nephropathy.
AB  - BACKGROUND: A considerable diversity of prognosis is seen with idiopathic
      membranous nephropathy (IMN). The initial factors affecting long-term outcome
      remain unclear. METHODS: We studied retrospectively 105 patients with IMN who had
      been followed up for at least 5 years, or until end-stage renal failure (ESRF)
      (primary outcome), or death (secondary outcome). We analyzed the initial
      clinicopathologic factors affecting primary and secondary outcomes. We assigned
      the patients to two groups and one subgroup, based on the electron microscopic
      findings. The groupings were: homogeneous type with synchronous electron dense
      deposits; homogeneous type with large dense deposits (deep subgroup); and
      heterogeneous type with various phases of dense deposits. RESULTS: No differences
      in the initial clinicopathologic states were seen between the homogeneous (N= 60)
      and heterogeneous types (N= 45), apart from hypertension and disease history
      before biopsy. In the homogeneous type, only one patient developed ESRF, which
      was drug-induced, and remission occurred earlier than in the heterogeneous type.
      With regard to secondary outcomes, increased age, male gender, heterogeneous
      type, and deep subgroup were independent risk factors. There were no significant
      differences attributable to therapeutic regime with respect to primary or
      secondary outcome in either group. CONCLUSION: Our results indicate that an
      electron microscopic classification, at initial biopsy, as heterogeneous type or
      deep subgroup type with dense deposits are independent indicators of poor
      prognosis in IMN.

PMID- 14675046
TI  - Calcium oxalate crystal localization and osteopontin immunostaining in genetic
      hypercalciuric stone-forming rats.
AB  - BACKGROUND: The inbred genetic hypercalciuric stone-forming (GHS) rats develop
      calcium phosphate (apatite) stones when fed a normal 1.2% calcium diet. The
      addition of 1% hydroxyproline to this diet does not alter the type of stone
      formed, while rats fed this diet with 3% hydroxyproline form mixed apatite and
      calcium oxalate stones and those with 5% hydroxyproline added form only calcium
      oxalate stones. The present study was designed to determine the localization of
      stone formation and if this solid phase resulted in pathologic changes to the
      kidneys. METHODS: GHS rats were fed 15 g of the standard diet or the diet
      supplemented with 1%, 3%, or 5% hydroxyproline for 18 weeks. A separate group of
      Sprague-Dawley rats (the parental strain of the GHS rats), fed the standard diet
      for a similar duration, served as an additional control. At 18 weeks, all kidneys
      were perfusion-fixed for structural analysis, detection of crystal deposits using
      the Yasue silver substitution method, and osteopontin immunostaining. RESULTS:
      There were no crystal deposits found in the kidneys of Sprague-Dawley rats.
      Crystal deposits were found in the kidneys of all GHS rats and this Yasue-stained
      material was detected only in the urinary space. No crystal deposits were noted
      within the cortical or medullary segments of the nephron and there was no
      evidence for tubular damage in any group. The only pathologic changes occurred in
      3% and 5% hydroxyproline groups with the 5% group showing the most severe
      changes. In these rats, which form only calcium oxalate stones, focal sites along
      the urothelial lining of the papilla and fornix of the urinary space demonstrated
      a proliferative response characterized by increased density of urothelial cells
      that surrounded the crystal deposits. At the fornix, some crystals were lodged
      within the interstitium, deep to the proliferative urothelium. There was
      increased osteopontin immunostaining in the proliferating urothelium. CONCLUSION:
      Thus in the GHS rat, the initial stone formation occurred solely in the urinary
      space. Tubular damage was not observed with either apatite or calcium oxalate
      stones. The apatite stones do not appear to cause any pathological change while
      those rats forming calcium oxalate stones have a proliferative response of the
      urothelium, with increased osteopontin immunostaining, around the crystal
      deposits in the fornix.

PMID- 14675047
TI  - Characterization of uremic toxin transport by organic anion transporters in the
      kidney.
AB  - BACKGROUND: Harmful uremic toxins, such as indoxyl sulfate (IS), 3-carboxy-4
      methyl-5-propyl-2-furanpropionate (CMPF), indoleacetate (IA), and hippurate (HA),
      accumulate to a high degree in uremic plasma. IS has been shown to be a substrate
      of rat organic anion transporter 1 (rOat1) and rOat3. However, the contribution
      of rOat1 and rOat3 to the renal uptake transport process of IS and other uremic
      toxins in the kidney remains unknown. METHODS: The cellular uptake of uremic
      toxins was determined using stable transfectants of rOat1/hOAT1 and rOat3/hOAT3
      cells. Also, the uptake of uremic toxins by rat kidney slices was characterized
      to evaluate the contribution of rOat1 and rOat3 to the total uptake by kidney
      slices using inhibitors of rOat1 (p-aminohippurate) and rOat3 (pravastatin and
      benzylpenicillin). RESULTS: Saturable uptake of IS, CMPF, IA, and HA by rOat1 was
      observed with Km values of 18, 154, 47, and 28 micromol/L, respectively, whereas
      significant uptake of IS and CMPF, but not of IA or HA, was observed in rOat3
      expressing cells with Km values of 174 and 11 micromol/L, respectively. Similar
      parameters were obtained for human OAT1 and OAT3. Kinetic analysis of the IS
      uptake by kidney slices revealed involvement of two saturable components with Km1
      (24 micromol/L) and Km2 (196 micromol/L) values that were comparable with those
      of rOat1 and rOat3. The Km value of CMPF uptake by kidney slices (22 micromol/L)
      was comparable with that of rOat3, while the corresponding values of IA and HA
      (42 and 33 micromol/L, respectively) were similar to those of rOat1. PAH
      preferentially inhibited the uptake of IA and HA by kidney slices, while
      pravastatin and benzylpenicillin preferentially inhibited the uptake of CMPF. The
      effect of these inhibitors on the uptake of IS by kidney slices was partial.
      CONCLUSIONS: rOat1/hOAT1 and rOat3/hOAT3 play major roles in the renal uptake of
      uremic toxins on the basolateral membrane of the proximal tubules. Both OAT1 and
      OAT3 contribute almost equally to the renal uptake of IS. OAT3 mainly accounts
      for CMPF uptake by the kidney, while OAT1 mainly accounts for IA and HA uptake.

PMID- 14675048
TI  - Down-regulation of Na+ transporters and AQP2 is responsible for acyclovir-induced
      polyuria and hypophosphatemia.
AB  - BACKGROUND: Acyclovir (ACY) is a useful therapeutic agent for the systemic
      treatment of herpes virus infection. An increase in urinary phosphate excretion
      and polyuria has been described. The objective of this study was to analyze the
      exact mechanism of the urinary-concentrating dysfunction and the increase in
      phosphaturia associated with ACY. METHODS: We first analyzed 7 (adult and
      pediatric) non-AIDS cases of encephalitis receiving 15 mg/kg bw/d of intravenous
      ACY. Fractional phosphate and sodium excretion, urinary potassium volume, and
      plasma phosphate concentrations were analyzed. Additional studies in rats treated
      with intraperitoneal ACY (100 mg/kg bw) were also conducted. Animals were
      maintained in metabolic cages and 24-hour urine samples were collected to measure
      volume, osmolality, and sodium/potassium/phosphate excretion. Treated rats were
      also evaluated after 24 hours and 48 hours of water deprivation. Northern
      hybridization and semiquantitative immunoblotting were performed to evaluate (in
      both control and treated animals) expression of the cotransporters Na-Pi type IIa
      (Na-Pi-IIa) and Na-K-2Cl (NKCC2). Semiquantitative immunoblotting was carried out
      in the kidneys of ACY rats and control rats in order to analyze aquaporin 2
      (AQP2) protein expression. RESULTS: Patients started on ACY developed polyuria
      and hyperphosphatemia after 48 hours. In rats, ACY-induced hyperphosphaturia and
      hypophosphatemia were accompanied by increased excretion of sodium, potassium,
      and magnesium, increased urine output, lower urinary osmolality, and a partial
      urinary concentrating defect. Concurrent downregulation of Na-Pi-IIa and NKCC2
      expression was observed. There was also a decrease in medullar expression of the
      AQP2 collecting duct water channel. CONCLUSION: Downregulation of Na-Pi-IIa
      appears to play a crucial role in the downregulation of ACY-induced
      hyperphosphaturia. The accompanying polyuria and urinary-concentrating defect can
      in part be explained by the downregulation of NKCC2 and AQP2.

PMID- 14675049
TI  - Short-term modulation of distal tubule fluid nitric oxide in vivo by loop NaCl
      reabsorption.
AB  - BACKGROUND: Intrarenal nitric oxide (NO) production and signaling effects are
      influenced by NaCl loading. To gain further insight into NO mechanisms we
      determined whether rat distal tubular fluid (DTF) [NO] and collected NO may
      acutely change when NaCl loop delivery is altered. METHODS: An NO microelectrode
      was used to measure real-time DTF [NO] and DT-collected NO. With proximal flow
      blocked (open system), 150 mmol/L NaCl, with and without 10(-4) mol/L furosemide
      was perfused with measurement of loop [Cl] reabsorption. Using a closed system,
      DTF [NO] was also determined using several different loop perfusates. RESULTS: In
      the open system, perfusion with 40 nL/min of 150 mmol/L NaCl to which 10(-4)
      mol/L furosemide was added, DT [NO] and DT-collected NO was approximately twice
      that measured with perfusion of 150 mmol/L NaCl alone, while loop Cl reabsorption
      decreased by half. In the closed system, perfusion at 10 nL/min of 150 mmol/L
      NaCl + furosemide 10(-4) mol/L also induced a significant rise in DTF [NO] and
      collected NO. Perfusion of 10(-3) mol/L S-methyl-L-thiocitrulline (SMTC) with 150
      mmol/L NaCl, induces a significant drop in DT [NO], but without a significant
      increase in collected NO. Furthermore, with addition of 10(-3) mol/L SMTC to the
      150 mmol/L NaCl + 10(-4) furosemide perfusate, the rise in DT [NO] was prevented.
      Analysis of covariance showed that flow changes within, or between all groups,
      had no significant additional effect. CONCLUSION: In both open and closed loop
      perfusion systems, 10(-4) mol/L furosemide inhibition of NaCl transport
      stimulates net loop NO emission independent of flow; 10(-3) mol/L SMTC + 150
      mmol/L NaCl reduces DT [NO], but not DT-collected NO. Short-term net NO emission
      from the entire loop, as collected in distal tubule fluid, increases with
      inhibition of loop NaCl transport.

PMID- 14675050
TI  - A common sequence variation of the CLCNKB gene strongly activates ClC-Kb chloride
      channel activity.
AB  - BACKGROUND: Tubular transepithelial reabsorption of chloride along the nephron is
      a major determinant of body salt and water homeostasis and blood pressure
      regulation. About 40% of the glomerulary filtered sodium chloride are reabsorbed
      in the distal nephrons. Vectorial transepithelial sodium chloride transport is
      critically dependent on the function of basolateral ClC-K type chloride channels
      there. Modulation of ClC-Kb chloride channel activity by polymorphic variations
      of the CLCNKB gene, thus, could form a molecular basis for salt sensitivity of
      blood pressure regulation. In this study we tested the effect of several
      polymorphic variants on ClC-Kb chloride channel activity. METHODS: After
      heterologous expression in Xenopus oocytes, ClC-Kb channel activity and surface
      expression in presence of the ClC-K beta subunit barttin were determined by two
      electrode voltage-clamp analysis, immunofluorescence, and ClC-Kb surface enzyme
      linked immunosorbent assay (ELISA). RESULTS: Chloride currents induced by the ClC
      Kb variants L27R, G214A, I419V, T562M, and E578K were not significantly different
      from wild-type currents. The ClC-KbT481S variation, however, which showed a
      frequency of 20% in our control population, dramatically activated chloride
      conductance by a factor of 20. Activation of chloride currents was also observed
      after introducing homologous mutations in ClC-Ka and ClC-K1, but not in ClC-2 and
      ClC-5 chloride channels. ClC-Kb activation by the T481S mutation did not change
      intrinsic ion channel pore properties and did not require increased surface
      expression of ClC-KbT481S. CONCLUSION: Genetic heterogeneity of ClC-Kb chloride
      channels correlates with functional heterogeneity, which assigns ClC-Kb to a set
      of genes potentially relevant for polygenic salt-sensitivity of blood pressure
      regulation.

PMID- 14675051
TI  - Comparative ontogeny, processing, and segmental distribution of the renal
      chloride channel, ClC-5.
AB  - BACKGROUND: The renal chloride channel ClC-5, which is responsible for Dent's
      disease, is coexpressed with the vacuolar H+-ATPase in proximal tubules (PT) and
      alpha-type intercalated cells (IC) of the mature kidney. Neonatal cases of Dent's
      disease suggest that ClC-5 distribution must be acquired before birth. However,
      the ontogeny of ClC-5, and its processing and segmental distribution with respect
      to related proteins during nephrogenesis remain unknown. METHODS: Immunoblotting,
      real-time polymerase chain reaction (RT-PCR), immunostaining, and deglycosylation
      studies were used to investigate the expression, distribution, and maturation of
      ClC-5 during mouse and human nephrogenesis, in comparison with H+-ATPase, type II
      carbonic anhydrase (CAII), and aquaporin-1 (AQP1). RESULTS: An early induction
      (E13.5-E14.5) of ClC-5 was observed in mouse kidney, with persistence at high
      levels through late nephrogenesis. This pattern contrasted with the progressive
      expression of H+-ATPase and AQP1, and the postnatal upregulation of CAII.
      Immunostaining showed expression of ClC-5 in ureteric buds and, from E14.5, its
      location in developing PT. From E15.5, ClC-5 codistributed with H+-ATPase in PT
      cells and alpha-type IC. In the human kidney, ClC-5 was detected from 12
      gestation weeks; its distribution was similar to that observed in mouse, except
      for a later detection in IC. Although mouse and human ClC-5 proteins are
      glycosylated, biochemical differences between fetal and adult proteins were
      observed in both species. CONCLUSION: The segmental expression of ClC-5 and H+
      ATPase is essentially achieved during early nephrogenesis, in parallel with the
      onset of glomerular filtration. These data give insight into PT and IC
      maturation, and explain early phenotypic variants of Dent's disease.

PMID- 14675052
TI  - Blood pressure lability and glomerulosclerosis after normotensive 5/6 renal mass
      reduction in the rat.
AB  - BACKGROUND: Hypertension plays a major role in the progression of both
      experimental and clinical chronic renal disease. However, the pathogenesis of the
      more slowly developing glomerulosclerosis that is seen even in the absence of
      overt hypertension, both in renal mass reduction models and in humans with
      chronic renal disease, remains controversial. METHODS: The relationship of such
      glomerulosclerosis to the ambient blood pressure profiles was examined in the
      normotensive approximately 5/6 surgical excision rat remnant kidney model. Blood
      pressure was radiotelemetrically monitored at 10-minute intervals for 15 to 16
      weeks ( approximately 15,000 blood pressure readings) in untreated rats (N= 13),
      or those treated with enalapril (N= 8), amlodipine (N= 9), or a combination of
      hydralazine, reserpine, and hydrochlorothiazide (N= 10). RESULTS: Even in these
      normotensive rats (systolic blood pressure <140 mm Hg), % glomerulosclerosis was
      significantly correlated with the overall average systolic blood pressure (r=
      0.62, P < 0.0001; N= 40). However, much stronger correlations were observed
      between glomerulosclerosis and the % systolic blood pressure readings >150 mm Hg
      (r= 0.77, P < 0.0001) and the standard deviation of the average systolic blood
      pressure (r= 0.87, P < 0.0001). CONCLUSION: These data indicate that pressure
      dependent injury mechanisms continue to contribute to glomerular injury even
      within the "normotensive" blood pressure range in rats with reduced renal mass.
      This most likely represents the consequence of the impairment of protective renal
      autoregulation and enhanced glomerular transmission of the blood pressure
      fluctuations into the hypertensive range characteristic of the conscious state in
      both experimental animals and in humans. Such pathophysiology supports the need
      for more aggressive and around-the-clock blood pressure control in chronic renal
      disease.

PMID- 14675053
TI  - Up-regulation of kidney NAD(P)H oxidase and calcineurin in SHR: reversal by
      lifelong antioxidant supplementation.
AB  - BACKGROUND: Spontaneously hypertensive rats (SHR) are born normotensive and
      develop hypertension (HTN) later in life (age 4 to 5 weeks). HTN in SHR is
      associated with and caused in part, by oxidative stress and renal interstitial
      inflammation. This study tested the hypothesis that lifelong antioxidant
      supplementation beginning at prenatal period may delay the onset and reduce the
      severity of HTN in SHR. The study further sought to explore the effect of diet
      modification on renal tissue NAD(P)H oxidase and calcineurin abundance. METHODS:
      Pregnant SHR and their offspring were fed either an antioxidant-fortified diet (a
      chow containing alpha-tocopherol 5000 IU/kg, ascorbic acid 500 ppm, selenium 2.76
      ppm, and zinc 350 ppm) or regular diet (alpha-tocopherol 40 IU/kg, selenium 0.2
      ppm, and zinc 70 ppm). Animals were observed for 24 weeks. Wistar-Kyoto rats fed
      either a regular or antioxidant diet served as control. RESULTS: Onset of HTN was
      delayed and severity of HTN was reduced in antioxidant-treated compared with
      untreated SHR. Markers of oxidative stress (i.e., plasma hydrogen peroxide, renal
      tissue malondialdehyde, and nitrotyrosine abundance) were elevated in untreated
      but not in antioxidant-treated SHR. gp91phox and p22phox subunits of NAD(P)H
      oxidase were markedly elevated in the renal cortex of untreated SHR and partially
      restored in the treated SHR. Similarly, renal calcineurin Aalpha and B subunits
      were elevated in untreated SHR and were partially restored in the treated SHR.
      Antioxidant therapy had no effect on the measured parameters in the WKY control.
      CONCLUSION: Lifelong consumption of antioxidant-rich diet ameliorates HTN and
      oxidative stress in SHR. This is associated with the reduction of superoxide
      generating enzyme, NAD(P)H oxidase, and immunoregulatory factor calcineurin.
      Antioxidant-rich diet appears to attenuate oxidative stress, not only by
      fortifying antioxidant defense capacity but also by lowering NAD(P)H oxidase,
      which is a major source of reactive oxygen species.

PMID- 14675054
TI  - Nephrotic livers secrete normal VLDL that acquire structural and functional
      defects following interaction with HDL.
AB  - BACKGROUND: Binding of very low-density lipoprotein (VLDL) isolated from serum of
      nephrotic rats VLDL to endothelial cells is defective. This defect is conferred
      on normal VLDL by prior incubation with high-density lipoprotein (HDL) from
      nephrotic, but not control rats. It is not known whether the defect is present in
      nascent VLDL (nVLDL) or is acquired after secretion. We test the hypothesis that
      VLDL is normal at the time of secretion from the liver and the defect in binding
      to endothelium is conferred following secretion through interaction with HDL.
      METHODS: nVLDL was synthesized by and collected from isolated perfused livers
      from either control or nephrotic rats. nVLDL was labeled with 3H-oleate to
      measure binding and 35S methionine to evaluate apolipoprotein exchange and
      composition. To test whether HDL conferred a binding defect, nVLDL was incubated
      with HDL obtained either from control or nephrotic rats prior to measurement of
      binding. To distinguish the effects of proteinuria from reduced albumin
      concentration we additionally incubated nVLDL with HDL obtained from rats with
      hereditary analbuminemia. Both HDL and VLDL were reisolated by centrifugation
      prior to subsequent binding and lipolysis determination. Exchange of 35S-labeled
      apolipoprotein E (apoE) among the subsequent VLDL and HDL fractions was
      determined. To determine the effect of HDL on lipolysis, HDL-treated VLDL was
      exposed to lipoprotein lipase-coated 96-well plates and 3H-oleate release
      measured. To establish whether differences in apoE content could explain the
      differences in binding and lipolysis, apoE was restored to nephrotic VLDL and
      lipolysis and binding were subsequently measured. RESULTS: Binding of nephrotic
      nVLDL was greater than control nVLDL (0.58 +/- 0.13 vs. 0.75 +/- 0.07 ng protein
      bound/mg cell protein) (P= 0.04, N= 6). Lipolysis was similarly elevated (0.091
      +/- 0.010 vs 0.064 +/- 0.002 nmol NEFA released/well/hour) (P < 0.05). Prior
      incubation with nephrotic HDL reduced binding of nVLDL obtained from either
      nephrotic or control livers (P= 0.02, N= 6). Treatment with nephrotic (vs.
      control) HDL reduced both binding (control nVLDL + control HDL, 0.64 +/- 0.02;
      control + nephrotic, 0.43 +/- 0.06; nephrotic + control, 0.69 +/- 0.05; and
      nephrotic + nephrotic, 0.62 +/- 0.04 mg VLDL protein/mg cell protein) and
      lipolysis (control nVLDL + control HDL, 0.053 +/- 0.004; control + nephrotic,
      0.038 +/- 0.004; nephrotic + control, 0.069 +/- 0.004; and nephrotic + nephrotic,
      0.062 +/- 0.004 nmol NEFA/well/hour) (P < 0.05 vs. nVLDL + control HDL) of nVLDL
      from either source. The apoE content of nVLDL coincubated with control HDL or
      analbuminemic HDL was increased compared nVLDL incubated with either no HDL or
      nephrotic HDL (P < 0.05). Similarly, the apoE/apoA-I ratio was reduced in HDL
      from nephrotic rats but not in HDL from controls (P < 0.05). Reintroduction of
      apoE to nephrotic VLDL resulted in increased binding. CONCLUSION: Unlike
      circulating VLDL, binding of nVLDL from isolated livers from nephrotic rats to
      endothelial cells is greater and its lipolysis is increased compared to control
      nVLDL. Decreased binding and lipolysis is conferred following incubation with HDL
      isolated from control, but not nephrotic rats and binding can be restored by
      reintroduction of apoE. Thus both defects are conferred on VLDL by exposure to
      HDL obtained from nephrotic animals, possibly a consequence of a failure of
      nephrotic HDL to enrich VLDL with apoE during clearance.

PMID- 14675055
TI  - Angiotensin II receptor blockade prevents acute renal sodium retention induced by
      low levels of orthostatic stress.
AB  - BACKGROUND: Depending on its magnitude, lower body negative pressure (LBNP) has
      been shown to induce a progressive activation of neurohormonal, renal tubular,
      and renal hemodynamic responses, thereby mimicking the renal responses observed
      in clinical conditions characterized by a low effective arterial volume such as
      congestive heart failure. Our objective was to evaluate the impact of angiotensin
      II receptor blockade with candesartan on the renal hemodynamic and urinary
      excretory responses to a progressive orthostatic stress in normal subjects.
      METHODS: Twenty healthy men were submitted to three levels of LBNP (0, -10, and 
      20 mbar or 0, -7.5, and -15 mm Hg) for 1 hour according to a crossover design
      with a minimum of 2 days between each level of LBNP. Ten subjects were randomly
      allocated to receive a placebo and ten others were treated with candesartan 16 mg
      orally for 10 days before and during the three levels of LBNP. Systemic and renal
      hemodynamics, renal sodium excretions, and the hormonal response were measured
      hourly before, during, and for 2 hours after LBNP. RESULTS: During placebo, LBNP
      induced no change in systemic and renal hemodynamics, but sodium excretion
      decreased dose dependently with higher levels of LBNP. At -20 mbar, cumulative 3
      hour sodium balance was negative at -2.3 +/- 2.3 mmol (mean +/- SEM). With
      candesartan, mean blood pressure decreased (76 +/- 1 mm Hg vs. 83 +/- 3 mm Hg,
      candesartan vs. placebo, P < 0.05) and renal plasma flow increased (858 +/- 52
      mL/min vs. 639 +/- 36 mL/min, candesartan vs. placebo, P < 0.05). Glomerular
      filtration rate (GFR) was not significantly higher with candesartan (127 +/- 7
      mL/min in placebo vs. 144 +/- 12 mL/min in candesartan). No significant decrease
      in sodium and water excretion was found during LBNP in candesartan-treated
      subjects. At -20 mbar, the 3-hour cumulative sodium excretion was + 4.6 +/- 1.4
      mmol in the candesartan group (P= 0.02 vs. placebo). CONCLUSION: Selective
      blockade of angiotensin II type 1 (AT1) receptors with candesartan increases
      renal blood flow and prevents the antinatriuresis during sustained lower body
      negative pressure despite a modest decrease in blood pressure. These results thus
      provide interesting insights into potential benefits of AT1 receptor blockade in
      sodium-retaining states such as congestive heart failure.

PMID- 14675056
TI  - Changes in renal blood flow reserve after angioplasty of renal artery stenosis in
      hypertensive patients.
AB  - BACKGROUND: Intra-arterial Doppler is a recent technique which allows assessment
      of distal vascular disease using measurements of intrarenal blood flow
      velocities. The purpose of this study was to evaluate intrarenal hemodynamics and
      renal blood flow reserve before and after percutaneous transluminal angioplasty
      (PTA) in hypertensive patients with unilateral atherosclerotic renal artery
      stenosis using intra-arterial Doppler. METHODS: Intra-arterial Doppler was
      performed during arteriography in 19 hypertensive patients (12 men; mean age, 64
      +/- 8 years) in "normal" and in "stenotic" kidneys at baseline, on isosorbide
      dinitrate, and after selective intra-renal papaverine injection, before, and
      after PTA. Doppler parameters analyzed were average peak velocity, maximum peak
      velocity, end diastolic velocity, and renal blood flow (RBF). Changes in Doppler
      parameters after papaverine injection were also analyzed. RESULTS: The major
      results were (1) the significant reduction in RBF distal to the stenosis, (2) the
      lack of arteriolar reactivity in response to papaverine distal to the stenosis,
      (3) the immediate recovery of arteriolar reactivity after PTA, associated with
      restoration of RBF in the revascularized kidneys, and (4) no change in arteriolar
      reactivity in response to papaverine in the "normal" kidneys following PTA.
      CONCLUSION: Ours results highlighted the benefit of endovascular Doppler to
      evaluate (1) RBF reserve, and (2) the repercussion of the stenosis on the distal
      vascularization.

PMID- 14675057
TI  - Delay of dialysis in end-stage renal failure: prospective study on percutaneous
      renal artery interventions.
AB  - BACKGROUND: Renal artery stenosis (RAS) is a cause of end-stage renal failure. We
      studied the effect of percutaneous renal artery intervention (PRI) in patients
      with advanced, progressive disease at risk for renal failure, hypothesizing a
      beneficial effect. METHODS: Thirty-nine primary and 14 secondary PRIs were
      performed on 28 patients with atherosclerotic RAS, serum creatinine >300
      micromol/L, and progressive loss of renal function >/=1 year before PRI. Renal
      function and RA patency were prospectively followed for 12 months after primary
      and secondary PRI. The intervention's effect on the progressive loss of renal
      function was calculated by comparing reciprocal slopes of serum creatinine
      against time before and after PRI. RESULTS: Progression of renal failure slowed
      significantly following PRI. Mean (+/-SE) slopes of reciprocal serum creatinine
      values were: 6.69 +/- 0.97 L micromol(-1) day(-1) (x10(-6)) before and 6.76 +/-
      3.03 L micromol(-1) day(-1) (x10(-6)) after PRI (P= 0.0007). Fifteen patients
      (53.5%) showed improvement or stabilization of progressive renal dysfunction. Out
      of 11 patients expected to become dialysis dependent within one year, 8 (72.7%)
      experienced an improvement in renal function sufficient to remain dialysis-free.
      Favorable outcome correlated with a lower creatinine level (P= 0.0137) and a more
      negative slope of progression (r= 0.49, P= 0.020) at entry. Mortality was 10.7%,
      and rate of local complications was 7.1%. Deterioration of renal function
      following PRI was suspected in 17.9% of patients. CONCLUSION: PRI may improve
      renal function and ultimately delay dialysis in patients with advanced renal
      failure. Possible advantages must be weighed against the risk of renal failure
      advancement and high procedure-related complication rate.

PMID- 14675058
TI  - Body mass index is associated with altered renal hemodynamics in non-obese
      healthy subjects.
AB  - BACKGROUND: Weight excess is associated with increased renal risk. Data in overt
      obesity suggest a role for altered renal hemodynamics. Whether body mass index
      (BMI) is also relevant to renal function in non-obese subjects is unknown.
      METHODS: We studied the relation between BMI and renal hemodynamics in 102
      healthy, non-obese (BMI <30 kg/m2) subjects [59 males, 43 females, mean age 39
      (18-69) years] in a post-hoc analysis of subjects evaluated as prospective kidney
      donors or as healthy volunteers in renal hemodynamic studies. RESULTS: Mean (+/
      SD) BMI was 24.0 +/- 2.8 kg/m2, mean arterial pressure (MAP) 93 +/- 11 mm Hg,
      glomerular filtration rate (GFR, iothalamate clearance) 111 +/- 19 mL/min/1.73
      m2, effective renal plasma flow (ERPF, hippuran clearance) 458 +/- 108
      mL/min/1.73 m2, FF (GFR/ERPF) 0.25 +/- 0.04. On univariate analysis, BMI
      correlated negatively with ERPF/1.73 m2 body surface area (BSA) (r=-0.46; P <
      0.001), GFR/1.73 m2 BSA (r=-0.24, P= 0.013) and positively with FF (r= 0.45, P <
      0.001), and age (r= 0.47, P < 0.001). On multivariate analysis both BMI and age
      were independent predictors of ERPF/1.73 m2 BSA (negative) and FF (positive, all
      P < 0.05). Age was the only predictor of GFR/1.73 m2 BSA (negative). Analyzed for
      renal function indexed for height (h), BMI correlated negatively with ERPF/h (r=
      0.274, P= 0.005), but not with GFR/h (r= 0.13, P= 0.899). On multivariate
      analysis both BMI (positive) and age (negative) were independent predictors for
      GFR/h (both P < 0.001). Age was the only predictor for ERPF/h (negative).
      Predictors for FF (BMI and age, both positive) were by definition unaltered.
      CONCLUSION: The impact of BMI on renal function is not limited to overt obesity,
      as in subjects with BMI <30 kg/m2 a higher BMI is associated with higher FF, that
      is, a higher GFR relative to ERPF. This suggests an altered afferent/efferent
      balance and higher glomerular pressure (i.e., a potentially unfavorable renal
      hemodynamic profile) that may confer enhanced renal susceptibility when other
      factors, such as hypertension or diabetes are superimposed.

PMID- 14675059
TI  - Prevalence of anemia in erythropoietin-treated pediatric as compared to adult
      chronic dialysis patients.
AB  - BACKGROUND: Recent guidelines recommend a target hemoglobin range of 11 to 12
      g/dL in pediatric and adult dialysis patients. We compared anemia prevalence in
      United States Medicare pediatric and adult dialysis patients. METHODS: Prevalent
      hemodialysis patients (0 to 19 years, pediatric: N= 1692; adult: N= 352,291) and
      peritoneal dialysis patients (pediatric: N= 597; adult: N= 39,136) treated with
      recombinant human erythropoietin (rHuEPO) from 1996 to 2000 were selected. Mean
      annual hemoglobin values were calculated by modality, age, sex, and race.
      RESULTS: Among hemodialysis patients, mean annual hemoglobin values less than 11
      g/dL were present in pediatric and adult patients during 54.1% versus 39.8%
      patient years, respectively (P < 0.0001); for peritoneal dialysis patients, 69.5%
      versus 55.1% (P < 0.0001). Mean hemoglobin values increased over time and were
      11.2, 11.5, 10.8, and 11.2 g/dL for pediatric and adult hemodialysis and
      peritoneal dialysis patients, respectively, in 2000. Pediatric hemodialysis
      patients received intravenous iron less frequently than adults (66.3% vs. 82.5%
      patient years; P < 0.0001). CONCLUSION: Hemoglobin values in rHuEPO-treated
      pediatric dialysis patients lagged behind those of adult patients, with pediatric
      patients achieving target hemoglobin values only a minority of the time (45.9%
      and 30.5% patient years, respectively, for hemodialysis and peritoneal dialysis).
      Trends show recent improvement in anemia treatment of children on dialysis.
      Still, further attention to and analysis of rHuEPO and iron therapy in pediatric
      dialysis patients is warranted.

PMID- 14675060
TI  - Adiponectin in renal disease: relationship to phenotype and genetic variation in
      the gene encoding adiponectin.
AB  - BACKGROUND: The prevalence of cardiovascular disease (CVD) and inflammation is
      high in patients with end-stage renal disease (ESRD). Adiponectin is an
      adipocytokine that may have significant anti-inflammatory and anti
      atherosclerotic effects. Low adiponectin levels have previously been found in
      patients with high risk for CVD. METHODS: In a cohort of 204 (62% males) ESRD
      patients aged 52 +/- 1 years the following parameters were studied: presence of
      CVD, body composition, plasma adiponectin (N= 107), cholesterol, triglycerides,
      HDL-cholesterol, serum leptin, high-sensitivity C-reactive protein (hs-CRP),
      urinary albumin excretion (UAE), and single-nucleotide polymorphisms (SNPs) in
      the apM1 gene at positions -11391, -11377, 45, and 276. Thirty-six age- (52 +/- 2
      years) and gender-matched (64% males) healthy subjects served as control
      subjects. RESULTS: Markedly (P < 0.0001) elevated median plasma adiponectin
      levels were observed in ESRD patients (22.2 microg/mL), especially type 1
      diabetic patients (36.8 microg/mL), compared to control subjects (12.2
      microg/mL). Log plasma adiponectin correlated to visceral fat mass (R=-0.29; P <
      0.01) and Log hs-CRP (R=-0.26; P < 0.01). In a stepwise (forward followed by
      backward) multiple regression model only type-1 diabetes (P < 0.001) and visceral
      fat mass (P < 0.05) were independently associated with plasma adiponectin levels.
      The adiponectin gene -11377 C/C genotype was associated with a lower prevalence
      of CVD (25 vs. 42%) compared to the G/C genotype. CONCLUSION: The present cross
      sectional study demonstrates that, whereas genetic variations seem to have a
      minor impact on circulating adiponectin levels, lower visceral fat mass and type
      1 diabetes mellitus are associated with elevated plasma adiponectin levels in
      ESRD patients. Furthermore, low levels of adiponectin are associated with
      inflammation in ESRD.

PMID- 14675061
TI  - Parathyroidectomy rates among United States dialysis patients: 1990-1999.
AB  - BACKGROUND: Medical therapy for secondary hyperparathyroidism (SHPTH) has evolved
      considerably during the past decade. It is not known how changes in medical
      therapy might impact the parathyroidectomy (PTX) rate among dialysis patients.
      Relatively low parathyroid hormone (PTH) levels have been found among elderly
      dialysis patients and those with diabetes. Clinical factors associated with
      differing PTX rates among United States dialysis patients have not been reported.
      We report PTX rates in the United States from 1990 to 1999 among persons with end
      stage renal disease, accounting for changes in patient characteristics. METHODS:
      Data from the United States Renal Database were utilized. Patients insured by
      Medicare or Medicaid and receiving renal replacement therapy between January 1,
      1990, and December 31, 1999 were considered for analysis. PTX was determined by
      ICD-9 procedure codes. Multivariate Poisson models were used to estimate adjusted
      PTX rates. RESULTS: The overall observed PTX rate in the study sample was 7.16
      per 1000 person-years at risk. After a slight rise during the early 1990s,
      adjusted PTX rates declined by approximately 30% between 1995 and 1999. Adjusted
      PTX rates were higher among patients who were younger, female, nondiabetic,
      receiving peritoneal dialysis, and those with a longer cumulative duration of
      dialysis. CONCLUSION: PTX rates have recently decreased in the United States,
      independent of changes in patient characteristics. The effectiveness of medical
      therapy in targeting secondary hyperparathyroidism may be improving. Younger,
      nondiabetic patients with a longer cumulative dialysis burden are at particularly
      high risk for PTX.

PMID- 14675062
TI  - Assessing renal graft function in clinical trials: can tests predicting
      glomerular filtration rate substitute for a reference method?
AB  - BACKGROUND: In clinical trials, comparison of renal graft function needs a
      rigorous determination of glomerular filtration rate (GFR). Since reference
      methods to measure GFR cannot be easily implemented, a number of tests predicting
      GFR are usually used. However, little is known about their validity in renal
      transplant patients. We aimed to compare the performances of six GFR tests with
      inulin clearance in this population. METHODS: Five hundred consecutive inulin
      clearances performed in 294 renal transplant recipients with stable renal
      function were retrospectively selected. For each of them, we computed six
      estimates: the 24-hour creatinine clearance, the Cockcroft-Gault, Walser,
      Jelliffe, Nankivell, and Levey formulas. Their respective performance was
      assessed by correlation (simple linear regression), accuracy (dispersion of true
      error), and agreement (Bland and Altman method). RESULTS: Each GFR test closely
      correlated with inulin clearance (P < 0.0001). Comparisons between pairs of GFR
      tests did not show any significant difference in accuracy between the Levey,
      Jelliffe, and Walser formulas. Conversely, each of these formulas demonstrated a
      significant lower dispersion (P < 0.005) than the others. Nevertheless, all GFR
      tests displayed considerable lack of agreement with limits of agreement over 40
      mL/min/1.73 m2 apart. The proportion of predicted GFR differing from inulin
      clearance by +/- 10 mL/min/1.73 m2, ranged from 34% for the Jelliffe formula to
      53% for the Nankivell's one. CONCLUSION: None of these formulas seems to be able
      to safely substitute for inulin clearance. In clinical trials, renal graft
      function should be preferably assessed using a reference method of GFR
      measurement.

PMID- 14675063
TI  - Free-water transport in fast transport status: a comparison between CAPD
      peritonitis and long-term PD.
AB  - BACKGROUND: Ultrafiltration failure (UFF) in continuous ambulatory peritoneal
      dialysis (CAPD) is a transient phenomenon during acute peritonitis and a
      permanent complication in long-term peritoneal dialysis (PD). The high solute
      transport rates during acute peritonitis are probably caused by an increased
      number of perfused peritoneal capillaries. Long-term PD is associated with an
      increased number of peritoneal microvessels, leading to an enlargement of the
      anatomic vascular surface area. This leads to high mass transfer area
      coefficients (MTAC) and to UFF. Impaired conductance to glucose, leading to a
      reduction in free-water transport, may be a contributing factor to UFF in long
      term PD. We hypothesized that UFF during acute peritonitis is, in the absence of
      permanent structural changes, only caused by an increased vascular surface area,
      while in long-term patients it is often the result of an increased surface area
      in combination with an impaired conductance to glucose. Therefore, the peritoneal
      transport parameters of patients with acute peritonitis were compared to those in
      long-term PD patients. METHODS: A standard peritoneal permeability analysis (SPA)
      was done in 10 PD patients during the first 48 hours after the diagnosis of
      peritonitis. The results were compared to those obtained in 10 long-term PD
      patients matched for the MTAC creatinine. In addition, the results of 8
      peritonitis patients were compared with SPA results of 8 recently started PD
      patients, matched for MTAC creatinine. RESULTS: Peritonitis patients had a deeper
      maximal dip in D/P sodium, corrected for diffusion, than long-term patients
      (0.058 vs. 0.039, P < 0.05). Most parameters of peritoneal fluid transport were
      not different, except that t50 (i.e., the time to reach 50% of the maximum
      transcapillary ultrafiltration) was reached earlier during the dwell in
      peritonitis than in long-term PD-128 versus 175 minutes, P < 0.05. This confirmed
      the difference in the shape of the intraperitoneal volume versus time curve,
      which was blunted in the long-term patients. No differences were found for the
      parameters of solute transport between peritonitis patients and recently started
      patients. CONCLUSION: In contrast to patients with long-term PD, the osmotic
      conductance to glucose is unaffected in peritonitis, despite the lower net
      ultrafiltration caused by high solute transport. This implies that impaired free-
      water transport in chronic PD must be regarded as a contributing factor to UFF.

PMID- 14675064
TI  - Nonsustained effect of short-term bisphosphonate therapy on bone turnover three
      years after renal transplantation.
AB  - BACKGROUND: We recently showed that two doses of 4 mg of zoledronic acid (ZOL)
      ameliorated the bone loss and improved bone histology within the first six months
      after kidney transplantation. The aim of the present study was to evaluate
      whether this early short-term intervention exhibited a sustained bone-sparing
      effect. METHODS: A homogenous group of 20 de novo renal transplant recipients
      were equally randomized to two infusions of 4 mg of ZOL or placebo at two weeks
      and three months after engraftment. Patients were followed up for three years by
      sequential determination of bone densitometry and specific biochemical markers.
      RESULTS: From month six to three years after transplantation, both treatment
      groups exhibited an improvement of bone mineralization. Femoral neck bone mineral
      density z-scores increased statistically significantly from -1.3 (2.6) to -0.2
      (3.6) in the placebo group and from -1.6 (2.9) to -1.2 (1.9) in the ZOL group
      (median, range). Biochemical parameters of osteoblast activity such as
      osteocalcin and bone-specific alkaline phosphatase did not increase significantly
      in both groups. Osteoprotegerin, a marker of osteoclast inhibition, was
      significantly elevated over the first six months in the ZOL group, but decreased
      to similar levels, as in the placebo group, over the next two and a half years.
      Other markers of osteoclast activity such as c-telopeptide of type 1 collagen,
      calcitonin, and intact parathyroid hormone were not different between six months
      and three years in either group. CONCLUSION: The early bone-sparing effect of
      short-term ZOL therapy confers no sustained benefit versus placebo at three year
      post-transplantation.

PMID- 14675065
TI  - Single-chain antibody fragment-based adsorbent for the extracorporeal removal of
      beta2-microglobulin.
AB  - BACKGROUND: Dialysis-related amyloidosis (DRA) is a frequent complication of end
      stage renal disease (ESRD) that has been associated with the accumulation of
      beta2-microglobulin (beta2-m). Removal of beta2-m results in the loss of
      important proteins due to the nonspecific nature of current therapies. Although
      whole antibodies can potentially be used to confer specificity to beta2-m removal
      from blood, single-chain variable region (scFv) antibody fragments could
      potentially offer several advantages as immunoadsorption ligands due to their
      size, genetic definition, ability to be expressed by microbes, and amenability
      for in vitro evolution. METHODS: An antihuman beta2-m scFv was constructed from
      the BBM.1 hybridoma and expressed by a yeast display vector. The binding affinity
      of the wild-type scFv fragment was quantified by flow cytometry analysis. Soluble
      scFv was expressed by a yeast secretion vector, purified, and immobilized onto
      agarose beads. The binding capacity of the immunoadsorbent was measured by
      equilibrating samples with saturating quantities of fluorescent beta2-m in serum.
      RESULTS: The displayed scFv possessed a nanomolar affinity (KD= 0.008 +/- 0.004
      mg-beta2-m/L). The immunoadsorbent exhibited an adsorption site density of 0.41
      +/- 0.01 mg beta2-m/mL settled gel. Under saturating conditions, the mass ratio
      of adsorbed beta2-m to immobilized antibody is 70% greater than any previous
      literature report for whole antibodies. Preliminary specificity experiments
      suggest that the scFv-based immunoadsorbent is specific toward human beta2-m.
      CONCLUSION: Recombinant DNA technology was successfully used to engineer an scFv
      based immunoadsorbent. Use of immobilized scFvs during hemodialysis may minimize
      loss of valuable proteins and facilitate the removal of macromolecules that are
      significantly larger than the molecular weight cut-off of the membrane.

PMID- 14675066
TI  - Urine protein profiling with surface-enhanced laser-desorption/ionization time-of
      flight mass spectrometry.
AB  - BACKGROUND: In the last few years there has been an increasing interest in
      exploring the human proteome. In particular, efforts have focused on developing
      strategies to generate reproducible protein maps of normal cells, tissues, and
      biologic fluids, from which studies can then compare protein expression between
      different groups (e.g., healthy individuals vs. those with a specific pathologic
      state). METHODS: Various extrinsic factors (instrument settings, matrix
      composition, urine storage post void, freeze-thaw cycles) and intrinsic factors
      (blood in urine, urine dilution, first-void vs. midstream urine) were analyzed
      with respect to their impact on urine protein profiling using surface-enhanced
      laser-desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS).
      RESULTS: Extrinsic factors that critically influenced reproducibility and peak
      detection of urine protein profiling were matrix composition and instrument
      settings, while freeze-thaw cycles had minimal impact. Midstream urines samples
      did not undergo changes in their protein profile when stored for three days at 4
      degrees C. Intrinsic factors that influenced normal urine protein profiling were
      blood in the urine and urine dilution. Female first-void urine had a
      significantly different ratio of proteins present compared to a midstream urine
      sample. Limitations of the SELDI-TOF-MS technique included ion suppression and
      quantification of individual proteins when protein composition was complex.
      CONCLUSION: SELDI-TOF-MS offers a unique platform for high throughput urine
      protein profiling; however, standardization of analysis conditions is critical,
      and both extrinsic and intrinsic factors must be taken into account for accurate
      data interpretation.

PMID- 14675067
TI  - Podocytes as a target for treatment with ACE inhibitors and/or angiotensin
      receptor blockers.

PMID- 14675068
TI  - Medical control of secondary hyperparathyroidism: we're not there yet.

PMID- 14675069
TI  - Comparing loop diuretics in chronic kidney disease.

PMID- 14675071
TI  - N2O anesthesia may exacerbate hyperhomocysteinemia and endothelial dysfunction in
      patients with renal impairment.

PMID- 14675072
TI  - Failure to follow K/DOQI guidelines decreases effectiveness of access flow
      surveillance.

PMID- 14675074
TI  - Markers of oxidative stress in uremia.

PMID- 14675076
TI  - Treatment of primary IgA nephropathy.

PMID- 14675077
TI  - Malignancy, thrombosis and Trousseau: the case for an eponym.

PMID- 14675078
TI  - A definite role for treatment with activated protein C in sepsis? Yes.

PMID- 14675079
TI  - A definite role for treatment with activated protein C in sepsis? Standard use is
      premature.

PMID- 14675080
TI  - Good things come in small packages for hemophilia.

PMID- 14675081
TI  - Prevention of venous thromboembolism after major orthopedic surgery: 'new'
      clinical trials for new antithrombotic agents.

PMID- 14675082
TI  - Induction of megakaryocytes to synthesize and store a releasable pool of human
      factor VIII.
AB  - von Willebrand factor (VWF) is a complex plasma glycoprotein that modulates
      platelet adhesion at the site of a vascular injury, and it also serves as a
      carrier protein for factor (F)VIII. As megakaryocytes are the only hematopoietic
      lineage to naturally synthesize and store VWF within alpha-granules, this study
      was performed to determine if expression of a FVIII transgene in megakaryocytes
      could lead to trafficking and storage of FVIII with VWF in platelet alpha
      granules. Isolex selected CD34+ cells from human G-CSF mobilized peripheral blood
      cells (PBC) and murine bone marrow were transduced with a retrovirus encoding the
      B-domain deleted form of human FVIII (BDD-FVIII). Cells were then induced with
      cytokines to form a population of multiple lineages including megakaryocytes.
      Chromogenic analysis of culture supernatant from FVIII-transduced human cells
      demonstrated synthesis of functional FVIII. Treatment of cells with agonists of
      platelet activation (ADP, epinephrine, and thrombin receptor-activating peptide)
      resulted in the release of VWF antigen and active FVIII into the supernatant from
      transduced cells. Immunofluorescence analysis of cultured human and murine
      megakaryocytes revealed a punctate pattern of staining for FVIII that was
      consistent with staining for VWF. Electron microscopy of transduced
      megakaryocytes using immunogold-conjugated antibodies colocalized FVIII and VWF
      within the alpha-granules. FVIII retained its association with VWF in human
      platelets isolated from the peripheral blood of NOD/SCID mice at 2-6 weeks post
      transplant of transduced human PBC. These results suggest feasibility for the
      development of a locally inducible secretory pool of FVIII in platelets of
      patients with hemophilia A.

PMID- 14675083
TI  - The direct thrombin inhibitor melagatran followed by oral ximelagatran compared
      with enoxaparin for the prevention of venous thromboembolism after total hip or
      knee replacement: the EXPRESS study.
AB  - BACKGROUND: Ximelagatran and its subcutaneous (s.c.) form melagatran are novel
      direct thrombin inhibitors for the prevention and treatment of thromboembolic
      disease. METHODS: In a double-blind study, 2835 consecutive patients undergoing
      total hip or knee replacement were randomized to either melagatran/ximelagatran
      or enoxaparin. Melagatran 2 mg was started immediately before surgery; 3 mg was
      then administered postoperatively, followed by 24 mg of oral ximelagatran b.i.d.
      beginning the next day. Enoxaparin 40 mg, administered subcutaneously o.d., was
      started 12 h before surgery. Both treatments were continued for 8-11 days. The
      main efficacy outcome measures were major venous thromboembolism (VTE); [proximal
      deep vein thrombosis (DVT), non-fatal and/or fatal pulmonary embolism (PE), death
      where PE could not be ruled out], and total VTE (proximal and distal DVT; PE;
      death from all causes). DVT was detected by mandatory bilateral ascending
      venography at the end of the treatment period or earlier if clinically suspected.
      The main safety outcome was bleeding. RESULTS: The rates of major and total VTE
      were significantly lower in the melagatran/ximelagatran group compared with the
      enoxaparin group (2.3% vs. 6.3%, P = 0.0000018; and 20.3% vs. 26.6%, P < 0.0004,
      respectively). Fatal bleeding, critical site bleeding and bleeding requiring
      reoperation did not differ between the two groups. 'Excessive bleeding as judged
      by the investigator' was more frequent with melagatran/ximelagatran than with
      enoxaparin. CONCLUSIONS: In patients undergoing total hip or knee replacement,
      preoperatively initiated s.c. melagatran followed by oral ximelagatran was
      significantly more effective in preventing VTE than preoperatively initiated s.c.
      enoxaparin.

PMID- 14675084
TI  - Heterologous cell-cell interactions: thromboregulation, cerebroprotection and
      cardioprotection by CD39 (NTPDase-1).
AB  - Blood platelets maintain vascular integrity and promote primary and secondary
      hemostasis following interruption of vessel continuity. Biochemical or physical
      damage to the coronary, carotid or peripheral arteries is followed by excessive
      platelet activation and recruitment culminating in vascular occlusion and tissue
      ischemia. Currently inadequate therapeutic approaches to stroke and coronary
      artery disease are a public health issue. Following our demonstration of
      neutrophil leukotriene production from arachidonate released from activated
      aspirin-treated platelets, we studied interactions between platelets and other
      blood cells, leading to concepts of transcellular metabolism and
      thromboregulation. Thrombosis has a proinflammatory component whereby
      biologically active substances are synthesized by interactions between different
      cell types that could not individually synthesize the product(s). Endothelial
      cells control platelet reactivity via three biochemical systems-autacoids leading
      to production of prostacyclin and nitric oxide, and endothelial ecto
      ADPase/CD39/NTPDase-1. The autacoids are fluid-phase reactants, not produced by
      tissues in the basal state. They are only synthesized intracellularly and
      released upon interactions of cells with an agonist. When released, autacoids
      exert fleeting actions in the immediate milieu, and are rapidly inactivated. CD39
      is an integral component of the endothelial cell surface and is substrate
      activated. It maintains vascular fluidity in the complete absence of prostacyclin
      and nitric oxide, indicating that they are ancillary components of hemostasis.
      Therapeutic implications for the autacoids have not been compelling because of
      their transient, local and fleeting action, and limited potency. Conversely,
      CD39, acting solely on the platelet releasate, is efficacious in three different
      animal models. It metabolically neutralizes a prothrombotic platelet releasate
      via deletion of ADP--the major recruiting agent responsible for formation of an
      occlusive thrombus. In addition, solCD39 reduced ATP- and ischemia-induced
      norepinephrine release in the heart. This reduction can prevent fatal arrhythmia.
      Moreover, solCD39 ameliorated the sequelae of stroke in CD39 null mice. CD39
      represents the next generation of cardioprotective and cerebroprotective
      molecules.

PMID- 14675085
TI  - Arthritis is linked to local and systemic activation of coagulation and
      fibrinolysis pathways.
AB  - BACKGROUND: Activation of coagulation and fibrinolysis play a role in the
      pathophysiology of experimental arthritis. OBJECTIVE: To determine the extent of
      activation of the coagulation and fibrinolytic pathways in different joint
      diseases in humans and to ascertain the factors that may influence fibrin
      deposition within the joint. METHODS: Plasma from normal subjects (controls, n=
      21) and plasma and synovial fluid samples from patients with rheumatoid arthritis
      (RA; n = 64), osteoarthritis (OA; n = 29), spondyloarthropathy (SpA; n = 22) and
      crystal arthritis (CA; n = 25) were analyzed for the levels of TF (tissue factor)
      and tissue factor pathway inhibitor (TFPI) activities, thrombin-antithrombin III
      (TAT) complexes, and F1 + 2 (thrombin fragment), fibrin d-dimer and thrombin
      activated fibrinolysis inhibitor (TAFI) antigenic levels. The measurements were
      analyzed by pairwise correlation with each other as well as with standard
      parameters of inflammation [C-reactive protein (CRP), joint leukocyte count].
      Inter-group comparisons were performed to look for disease-specific differences.
      RESULTS: Compared with healthy controls, patients with joint diseases had higher
      levels of TAT, F1 + 2 and d-dimers in their plasma. In the synovial fluid, TF
      activity, TAT, d-dimers, and TAFI were significantly higher in inflammatory
      arthritides than in OA. The levels were highest in RA patients. In the plasma, TF
      activity was correlated with TAT and d-dimer levels with CRP, TFPI, and TAT. In
      the synovial fluid, TF activity correlated with plasma CRP levels, synovial fluid
      leukocyte count, and synovial TAT and TAFI levels. In addition, synovial d-dimers
      correlated with CRP, and synovial TAFI levels were correlated with synovial F1 +
      2 and TAT. CONCLUSIONS: Activation of the coagulation and fibrinolytic cascades
      in the joint and in the circulation is evident in both inflammatory and
      degenerative joint diseases. Within the joint, inflammatory mechanisms leading to
      TF-mediated activation of the coagulation pathway and subsequent fibrin
      deposition is the most likely explanation for the observed findings. In the
      plasma, the link between inflammation (CRP increase) and TF activation is weak,
      and a non-TF-mediated mechanism of coagulation activation could explain these
      findings. RA is characterized by significantly higher levels of TAT in the
      synovial fluid and plasma than other arthritides. Although fibrinolytic activity
      is linked to inflammation, the increased amounts of TAFI in the joint,
      particularly in RA, may explain why fibrin formation is so prominent in this
      condition compared with other joint diseases.

PMID- 14675086
TI  - Pediatric venous thromboembolic disease in one single center: congenital
      prothrombotic disorders and the clinical outcome.
AB  - To learn more about the frequencies of congenital prothrombotic disorders in
      pediatric venous thromboembolism (VTE) and the outcome of this disease, we
      evaluated consecutive patients from 0 to 18 years with objectively diagnosed VTE
      at a single tertiary center over a 12-year period. We included 100 patients, with
      a median age at diagnosis of 1.0 year (range 2 days to 17 years). At least one
      underlying clinical condition was present in 96% of the patients. Factor (F)V
      G1691A mutation was present in 13%, FII G20210A mutation in 3%, antithrombin
      deficiency in 1%, protein C deficiency in 1% and protein S deficiency in 1% of
      the tested patients. Combined defects were present in 2.6% of the 77 patients
      with a complete work-up. Positive family history appeared to be the only
      predictor for positive testing for congenital disorders (OR 14.9, 95% CI 1.9
      113). The overall mortality rate was 20%. The cumulative recurrence-free survival
      was 92% after 1 year of follow-up, and 82% after 7 years. The incidence and
      severity of the post-thrombotic syndrome was analyzed in a subgroup of 33
      patients with VTE of the lower extremities. Twenty-three (70%) patients developed
      PTS: moderate in three and mild in 20 patients. In conclusion, congenital
      prothrombotic disorders seem to play a role in the development of pediatric VTE,
      and the risk of complications of this disease is high.

PMID- 14675087
TI  - Individualized duration of oral anticoagulant therapy for deep vein thrombosis
      based on a decision model.
AB  - BACKGROUND: The optimal duration of oral anticoagulant therapy for patients with
      a first episode of deep vein thrombosis (DVT) is still a matter of debate.
      However, according to the ACCP consensus strategy a limited stratification in
      treatment duration is advocated, i.e. 3 months for patients with a transient risk
      factor and 1 year or longer for patients with recurrent disease or a consistent
      risk factor such as thrombophilia or cancer. This consensus strategy is founded
      on the mean optimal duration of therapy obtained in large cohorts of patients and
      is mainly based on the risk of recurrent venous thromboembolism (VTE), with only
      minimal consideration for the patient's bleeding risk. OBJECTIVE: The aim of this
      study is to optimize the anticoagulant treatment strategy with vitamin K
      antagonists for the individual patient with DVT. METHODS: Based on an extensive
      literature study, a mathematical model was constructed to balance the risk of
      recurrent VTE against the risk of major hemorrhagic complications. The following
      parameters are incorporated in the model: baseline estimates and risk factors for
      recurrent VTE and bleeding, clinical course of DVT, and efficacy of treatment
      with vitamin K antagonists. With the use of these parameters, the risk for a
      recurrent VTE and a bleeding episode can be calculated for the individual
      patient. The optimal duration of anticoagulant therapy can be defined as the
      timepoint at which the benefit of treatment (prevention of VTE) is
      counterbalanced by its risk (bleeding). RESULTS/CONCLUSIONS: How long a patient
      should receive anticoagulant treatment is a matter of balancing the benefits and
      risks of treatment. The model shows that the optimal treatment duration varies
      greatly from patient to patient according to the patient's unique bleeding and
      recurrence risk.

PMID- 14675088
TI  - Increased hemostasis potential persists in women with previous thromboembolism
      with or without APC resistance.
AB  - BACKGROUND: Activated thrombin generation and depressed fibrinolysis due to the
      presence of activated protein C (APC) resistance with or without factor (F)V
      Leiden mutation are associated with development of deep venous thrombosis (DVT).
      OBJECTIVE: A better understanding of the mechanism behind the risk of recurrence
      of DVT, using our new, recently developed assay of overall hemostasis potential
      (OHP). PATIENTS AND METHODS: Levels of OHP, as well as APC resistance and FV
      Leiden mutation, were determined in 88 women (cases) who had previously
      experienced DVT in connection with pregnancy, and in 25 young healthy individuals
      (controls). Clotting time and clot lysis time were also investigated. RESULTS:
      OHP levels in the patients were increased compared with the controls. In the
      cases with APC resistance and the Leiden mutation this imbalance in hemostasis
      potential was more severe than in those without. The group with the more severe
      imbalance had shorter clotting times and longer clot lysis times. CONCLUSIONS: A
      procoagulant state perseveres in patients with a history of pregnancy-related
      DVT, even after the symptomatic phase is over. The mechanisms behind such an
      imbalance in overall hemostasis are enhanced thrombin generation and depressed
      fibrinolysis. These findings may underscore the need for thromboprophylaxis to
      prevent recurrence of thromboembolism in risk situations.

PMID- 14675089
TI  - Elevated plasma levels of factor VIII in women with early recurrent miscarriage.
AB  - AIMS: Inherited and acquired thrombophilia have been found to be associated with
      recurrent pregnancy loss. This paper examines whether or not elevated factor
      (F)VIII:C plasma levels, which have been demonstrated to be an independent risk
      factor for venous thromboembolism, are a risk factor for early recurrent
      miscarriages also. PATIENTS AND METHODS: Consecutive women referred to our clinic
      with a history of early recurrent abortion (at least three pregnancy losses
      before week 13 of gestation) were eligible for the study. Exclusion criteria were
      endocrine, immunological, anatomical and genetic causes of embryo demise, as well
      as any thrombophilic abnormality, either congenital or acquired, or a personal or
      familial history of venous thromboembolism. FVIII:C plasma levels were determined
      in 51 cases and in 51 controls matched for age, ethnicity and blood group.
      RESULTS: The mean FVIII:C level in the control subjects was 106.8 IU dL-1,
      compared with 128.2 IU dL-1 in the patients group (P = 0.0002). Thirteen (25.5%)
      of the 51 patients had FVIII:C values exceeding the 90th centile of the control
      population (145 IU dL-1), compared with four subjects in the control group (chi2
      = 4.52; P = 0.033; odds ratio = 4.02, 95% confidence interval 1.09, 16.05). No
      cases with increase in FVIII:C levels attributable to an acute-phase reaction, as
      assessed by C-reactive protein plasma concentration, were found. CONCLUSIONS: We
      found FVIII:C levels significantly higher in women with early recurrent
      miscarriage compared with controls. This finding suggests a possible association
      between this thrombophilic condition and early reproductive failures.

PMID- 14675090
TI  - Homocysteine levels are associated with the severity of peripheral arterial
      disease in Type 2 diabetic patients.
AB  - BACKGROUND: Homocysteine levels are positively associated with the risk of
      cardiovascular disease. They might be determined by both MTHFR677C-->T
      polymorphisms and folate or B-vitamin status. OBJECTIVES: To investigate the
      possible association between plasma homocysteine levels and its genetic or
      environmental determinants and either the presence or the severity of peripheral
      arterial disease (PAD), in Type 2 diabetic patients. METHODS: From a cohort of
      944 patients with Type 2 diabetes, 135 patients with PAD were selected, and
      frequency-matched for age and sex with 219 Type 2 diabetic control patients
      without macrovascular complications. According to the increasing severity of the
      disease, patients were divided into PAD1 (only diffuse calcifications of the
      arteries without any stenosis or occlusion), PAD2 (one or two stenosis or
      occlusions) and PAD3 (three or more). RESULTS: Homocysteine levels were similar
      in control and case patients (10.3 micromol L-1 vs. 10.7 micromol L-1, P = 0.53);
      however, a significant increase was found in PAD3 patients: odds ratio = 2.77
      (95% confidence interval 1.14, 6.72) for patients with homocysteine levels above
      the median vs. those under the median in multivariate analysis. Although all
      significantly associated with homocysteine levels, neither MTHFR genotype nor
      folic acid or vitamin B12 levels were associated with severity of PAD. A
      significant interaction (P < 0.05) was found between folic acid and MTHFR
      polymorphism in determining the levels of homocysteine. CONCLUSIONS: In Type 2
      diabetes, homocysteine was associated with the angiographic severity of PAD, but
      neither the genotypes nor vitamin levels contributed to this association.

PMID- 14675091
TI  - Low detection rate of antibodies to non-functional epitopes on factor VIII in
      patients with hemophilia A and negative for inhibitors by Bethesda assay.
AB  - In patients with hemophilia A who have an inhibitor to factor (F)VIII measured by
      Bethesda assay, enzyme-linked immunosorbent assay (ELISA) can also be used to
      detect the inhibitor. In some studies non-inhibitory antibodies were also
      detected by ELISA in many patients who were negative by Bethesda assay. Our aim
      was to investigate whether there is a higher detection rate of FVIII antibodies
      by ELISA compared with Bethesda assay. We also compared outcomes using three
      different preparations of recombinant FVIII (rFVIII) to coat the microtiter
      plates for ELISA. Inhibitor detection by ELISA generally agreed with the Bethesda
      method. Only four of 26 patients with no clinical suspicion of an inhibitor and
      with no detectable inhibitor by Bethesda assay showed a non-inhibitory antibody
      by ELISA, and three of these were only weakly positive. Patients with severe
      hemophilia A and the intron 22 inversion (n = 21) did not show a higher incidence
      of non-inhibitory antibodies compared with those without that mutation. Finally,
      we found that the formulation of rFVIII has a small effect on ELISA performance,
      mainly in detection of low-level antibody. The results of the present study are
      in contrast to and fail to confirm previously published reports showing a higher
      incidence of non-inhibitory antibodies in hemophilia A.

PMID- 14675092
TI  - Nicotinamide inhibits endotoxin-induced monocyte tissue factor expression.
AB  - BACKGROUND: Tissue factor (TF) is the main initiator of blood coagulation in
      vivo. Its increased expression on activated monocytes is associated with
      thrombotic complications and mortality in conditions such as sepsis, disseminated
      intravascular coagulation and coronary artery disease. OBJECTIVE: The effect of
      the vitamin B derivative nicotinamide on endotoxin-induced monocyte TF and CD11b
      expression, soluble interleukin(IL)-6, and clotting onset time (COT) was studied.
      METHODS: Experiments were conducted in human peripheral blood leukocyte
      suspensions and in whole blood from eight healthy volunteers. Free oscillating
      rheometry (measuring COT) and flow cytometry were applied to evaluate the effect
      of endotoxin on TF, CD11b, IL-6 and the overall coagulation response of plasma
      supplemented with activated autologous leukocytes. RESULTS: In response to
      endotoxin, there was an increase in IL-6, TF and CD11b expression and a
      procoagulant shift of COT. At 4 mmol L-1 nicotinamide, inhibition of TF
      expression and IL-6 and a normalization of COT were seen. At 16 mmol L-1
      nicotinamide, CD11b decreased also. The level of monocyte TF expression
      correlated with the COT readings, and the endotoxin-induced procoagulant shift of
      COT could be totally inhibited by blocking TF with an inhibitory antibody.
      CONCLUSIONS: These results demonstrate the ability of nicotinamide to inhibit the
      activation of coagulation associated with endotoxemia. We have previously shown
      that nicotinamide exerts strong anti-inflammatory effects. Evidence is
      accumulating for nicotinamide to have a therapeutic potential in modulating
      disease states in which there is a profound activation of coagulation and
      inflammation, such as in sepsis and disseminated intravascular coagulation.

PMID- 14675093
TI  - Superantigens from Staphylococcus aureus induce procoagulant activity and
      monocyte tissue factor expression in whole blood and mononuclear cells via IL-1
      beta.
AB  - BACKGROUND: Staphylococcus aureus is one of the most common bacteria in human
      sepsis, a condition in which the activation of blood coagulation plays a critical
      pathophysiological role. During severe sepsis and septic shock microthrombi and
      multiorgan dysfunction are observed as a result of bacterial interference with
      the host defense and coagulation systems. OBJECTIVES: In the present study,
      staphylococcal superantigens were tested for their ability to induce procoagulant
      activity and tissue factor (TF) expression in human whole blood and in peripheral
      blood mononuclear cells. METHODS AND RESULTS: Determination of clotting time
      showed that enterotoxin A, B and toxic shock syndrome toxin 1 from S. aureus
      induce procoagulant activity in whole blood and in mononuclear cells. The
      procoagulant activity was dependent on the expression of TF in monocytes since
      antibodies to TF inhibited the effect of the toxins and TF was detected on the
      surface of monocytes by flow cytometry. In the supernatants from staphylococcal
      toxin-stimulated mononuclear cells, interleukin (IL)-1 beta was detected by
      ELISA. Furthermore, the increased procoagulant activity and TF expression in
      monocytes induced by the staphylococcal toxins were inhibited in the presence of
      IL-1 receptor antagonist, a natural inhibitor of IL-1 beta. CONCLUSIONS: The
      present study shows that superantigens from S. aureus activate the extrinsic
      coagulation pathway by inducing expression of TF in monocytes, and that the
      expression is mainly triggered by superantigen-induced IL-1 beta release.

PMID- 14675094
TI  - Highly accumulated platelet vascular endothelial growth factor in coagulant
      thrombotic region.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial cell
      specific potent mitogen that induces angiogenesis and microvascular
      hyperpermeability. Recently, it has been reported that megakaryocytes and
      platelets contain VEGF in their cytoplasm. OBJECTIVES: To elucidate and confirm
      the bioactivity and role of VEGF in platelets (platelet VEGF), which may be
      closely related to vascular thrombosis and atherosclerosis. METHODS: The VEGF
      localization in megakaryocytes on bone marrow smears was analyzed by
      immunofluorescence and confocal laser scanning microscopic analysis. The
      intracellular VEGF expressed in platelets was determined by flow cytometric
      analysis. Platelet-rich plasma and washed platelets were used to analyze the
      secretion of VEGF during platelet aggregation by thrombin or gelatinase A (matrix
      metalloproteinase-2) stimulation. Immunohistochemical studies for VEGF in the
      thrombotic region were performed. RESULTS AND CONCLUSIONS: Megakaryocytes and
      platelets are a very rich source of circulating VEGF. Gelatinase A, which is
      closely associated with vascular remodeling, enhances the VEGF levels released
      from platelets. VEGF was clearly detected in the fibrin nets of a thrombus. Taken
      together, platelet VEGF is bioactive as a direct angiogenic growth factor, and
      may play a very important role in wound healing and atherosclerosis in
      conjunction with other platelet cytokines such as platelet-derived growth factor,
      platelet-derived endothelial cell growth factor, transforming growth factor (TGF)
      alpha, and TGF-beta.

PMID- 14675095
TI  - A monoclonal antibody to the fibrinogen gamma-chain alters fibrin clot structure
      and its properties by producing short, thin fibers arranged in bundles.
AB  - BACKGROUND: We previously reported that hamster monoclonal antibody 7E9, which
      reacts with the C-terminus of the gamma-chain of mouse fibrinogen, inhibits
      factor (F)XIIIa-mediated cross-linking, platelet adhesion to fibrinogen, and
      platelet-mediated clot retraction; in addition, it facilitates thrombolysis.
      OBJECTIVES: To understand the mechanism(s) by which 7E9 acts, we have now studied
      the effect of 7E9 IgG, 7E9 F(ab')2, and 7E9 Fab on fibrin clot structure using
      electron microscopy and measurements of clot physical properties. RESULTS: By
      transmission electron microscopy, 7E9 IgG was found to bind primarily to the ends
      of the fibrinogen molecule. 7E9 IgG and 7E9 F(ab')2, both of which are bivalent,
      were capable of binding to two fibrinogen molecules simultaneously. Scanning
      electron microscopy of clots formed in the presence of equimolar concentrations
      of fibrinogen and 7E9 IgG demonstrated the presence of very short and thin fibers
      (63% reduction in fiber diameter) arranged in unusual bundles, surrounding large
      pores. Clots formed in the presence of 7E9 demonstrated a marked increase in
      permeation (approximately 25-fold increase in perfusion rate at constant
      pressure), an approximately 50% reduction in dynamic storage modulus (G'; a
      reflection of decreased clot stiffness), and an approximately 38% increase in
      loss tangent (tan delta; a reflection of the clot's ability to undergo
      irreversible deformation). These clots also showed decreased absorbance at 350
      nm, reflecting the clot structure produced by 7E9 IgG. The effects of 7E9 IgG
      were not observed with control hamster IgG, 7E9 F(ab')2, or 7E9 Fab fragments,
      indicating requirements for both the binding properties and mass of 7E9 IgG.
      CONCLUSIONS: These data indicate that 7E9 antibody affects fibrin clot structure
      in a way that is consistent with the enhanced fibrinolysis we reported
      previously. Together with our previous observations, we conclude that 7E9 is
      directed at a strategically important region of fibrinogen with regard to
      platelet function, FXIIIa-mediated cross-linking, clot retraction, fibrin
      structure, and fibrinolysis. Thus targeting this region of fibrinogen may have
      antithrombotic therapeutic potential.

PMID- 14675096
TI  - Problems relating to the laboratory diagnosis of factor XIII deficiency: a UK
      NEQAS study.
AB  - Familial (F)XIII deficiency is an extremely rare bleeding disorder. In most
      laboratories the diagnosis is initially established through a clot-solubility
      screening test. We report here results from a series of UK NEQAS (Blood
      Coagulation). Proficiency Testing investigations, in which laboratories were
      provided with samples from normal individuals and from various subjects with
      FXIII deficiency with a request to perform their usual test for this disorder and
      to provide an interpretation of their results. Over 95% of centers were able to
      diagnose severe familial FXIII deficiency in previously untreated patients and to
      identify samples from normal subjects. However, both quantitative and qualitative
      methods produced widely variable results on samples obtained from previously
      treated individuals with FXIII deficiency but having measurable levels of FXIII.
      Data generated by UK NEQAS investigations suggested that solubility tests
      employing thrombin show greater sensitivity to FXIII deficiency, and this was
      confirmed in a subsequent single-center study. Our results lead us to recommend
      the use of thrombin and acetic acid in the clot-solubility screening test. Use of
      sensitive screening tests, and improvement in the accuracy and precision of
      quantitative FXIII assays will aid study of the clinical importance of moderate
      FXIII deficiency.

PMID- 14675097
TI  - DNA variation in a 13-Mb region including the F9 gene: inferring the genealogical
      history and causal role of a hemophilia B mutation (IVS 5+13 A-->G).
AB  - About 5.5% of all UK hemophilia B patients have the base substitution IVS 5+13 A-
      >G as the only change in their factor (F)IX gene (F9). This generates a novel
      donor splice site which fits the consensus better than the normal intron 5 donor
      splice. Use of the novel splice site should result in a missense mutation
      followed by the abnormal addition of four amino acids to the patients' FIX. In
      order to explain the prevalence of this mutation, its genealogical history is
      examined. Analysis of restriction fragment length polymorphism in the 21
      reference UK individuals (from different families) with the above mutation showed
      identical haplotypes in 19 while two differed from the rest and from each other.
      In order to investigate the history of the mutation and to verify that it had
      occurred independently more than once, the sequence variation in 1.5-kb segments
      scattered over a 13-Mb region including F9 was examined in 18 patients and 15
      controls. This variation was then analyzed with a recently developed Bayesian
      approach that reconstructs the genealogy of the gene investigated while providing
      evidence of independent mutations that contribute disconnected branches to the
      genealogical tree. The method also provides minimum estimates of the age of the
      mutation inherited by the members of coherent trees. This revealed that 17 or 18
      mutant genes descend from a founder who probably lived 450 years ago, while one
      patient carries an independent mutation. The independent recurrence of the
      IVS5+13 A-->G mutation strongly supports the conclusion that it is the cause of
      these patients' mild hemophilia.

PMID- 14675098
TI  - Activated protein C attenuates coagulation-associated over-expression of
      fibrinolytic activity by suppressing the thrombin-dependent inactivation of PAI
      1.
AB  - Several activated coagulation factors have been reported to enhance fibrinolysis
      by neutralizing plasminogen activator inhibitor type 1 (PAI-1) activity. We
      evaluated the physiological relevance of this mechanism using the euglobulin clot
      lysis time (ECLT) assay in the presence and absence of Ca2+, which is controlled
      by PAI-1 and mimics physiological thrombolysis. We found that the ECLT (18.5 +/-
      0.6 h) was shortened by Ca2+ (5 mm) (6.6 +/- 0.1 h). A significant difference was
      observed in thrombin generation by the presence of Ca2+ in the euglobulin
      fraction. Prothrombin was almost fully converted to thrombin within 15 min in the
      presence of Ca2+, whereas essentially no conversion was observed without Ca2+.
      The presence of activated protein C (aPC) suppressed thrombin generation, and
      attenuated the shortening of ECLT in a dose-dependent manner, an effect enhanced
      by phospholipid and protein S. In the absence of Ca2+, aPC did not prolong the
      ECLT. After addition of biotin-labeled recombinant PAI-1 to the euglobulin
      fraction, PAI-1 was cleaved to lower molecular weight forms only in the presence
      of Ca2+. This cleavage did not occur in the presence of aPC, suggesting that
      thrombin was the catalyst for PAI-1 cleavage. The cleavage and inactivation of
      PAI-1 by generated thrombin is proposed to be responsible for the shortening of
      ECLT by Ca2+ and for coagulation-associated over-expression of fibrinolysis.
      Under such conditions, aPC appeared to suppress thrombin generation and to
      normalize highly activated fibrinolysis.

PMID- 14675099
TI  - Safety of plasmin in the setting of concomitant aspirin and heparin
      administration in an animal model of bleeding.
AB  - Plasmin is a direct thrombolytic which has been shown to have a strikingly
      favorable benefit to risk profile in comparison with plasminogen activators,
      notably tissue plasminogen activator (t-PA). As heparin is known to increase the
      risk of hemorrhage when co-administered with a plasminogen activator, we asked
      whether adjunct antithrombotic agents such as aspirin and heparin would affect
      the safety of plasmin. Three groups of rabbits were administered plasmin at a
      dose (4 mg kg-1) designed to induce significant decreases in antiplasmin,
      fibrinogen and factor (F)VIII, to about 25, 40 and 40%, respectively, of baseline
      values, but not cause prolongation of the ear puncture bleeding time. In a
      blinded and randomized trial, the results show that an intravenous aspirin bolus
      plus heparin administered as a bolus followed by a maintenance continuous
      infusion did not significantly prolong the bleeding time during plasmin infusion.
      These data indicate that in the rabbit, concomitant use of aspirin plus heparin
      does not affect the safety of a therapeutic dose of plasmin.

PMID- 14675100
TI  - Potentiation of platelet activation through the stimulation of P2X1 receptors.
AB  - The platelet P2X1 purinergic receptor is a ligand-gated ion channel that responds
      to ATP. The precise role of P2X1 in platelet function is unknown, though
      stimulation with the P2X1 agonist alpha,beta-Me-ATP is known to result in
      platelet shape change through elevation of calcium levels. The aim of the present
      study was to examine further the effects of P2X1 stimulation on platelet
      activation. Stimulation of P2X1 with alpha,beta-Me-ATP resulted in shape change
      and small aggregate formation in heparin-anticoagulated platelet preparations.
      Given the ability of heparin to potentiate platelet activation, subsequent
      experiments were performed in hirudin. In these platelet preparations, aggregate
      formation in response to alpha,beta-Me-ATP alone was less than that observed in
      heparin; however, alpha,beta-Me-ATP significantly potentiated platelet aggregate
      formation when added in conjunction with other weak platelet agonists
      [epinephrine or thrombopoietin (TPO)]. Platelet aggregate formation was confirmed
      by single platelet loss (microaggregate formation), microscopy, and light
      transmittance studies. Further, the P2X1 antagonist MRS-2159 inhibited platelet
      shape change and aggregation responses induced by alpha,beta-Me-ATP. Overall,
      this study demonstrates that P2X1 stimulation can induce/potentiate platelet
      activation in combination with other platelet agonists. These results are the
      first demonstration of platelet aggregation mediated through direct P2X1
      stimulation, supporting a role for this receptor in regulating platelet
      activation.

PMID- 14675101
TI  - A palmitylated peptide derived from the glycoprotein Ib beta cytoplasmic tail
      inhibits platelet activation.
AB  - The platelet receptor GPIb/IX/V mediates a crucial role in hemostasis, yet the
      signaling mechanisms involved are incompletely understood. The complex consists
      of four polypeptides GPIb alpha, GPIb beta, GPIX and GPV. We identified an amino
      acid sequence in the cytoplasmic tail of the GPIb beta subunit between residues
      R151 and A161 that is highly conserved across species and hypothesized that it
      has functional importance. To target this motif, we synthesized a corresponding
      cell-permeable palmitylated peptide (Pal-RRLRARARARA) and investigated its effect
      on platelet function. Pal-RRLRARARARA completely inhibited low dose thrombin- and
      ristocetin-induced aggregation in washed platelets but only partially inhibited
      collagen- and U46619-induced aggregation. Thromboxane production in platelets
      stimulated with thrombin was significantly reduced by Pal-RRLRARARARA compared
      with collagen. Activation of the integrin alpha IIb beta 3 in response to
      thrombin was significantly reduced when platelets were preincubated with Pal
      RRLRARARARA. The adhesion of washed platelets to von Willebrand factor (VWF)
      under static conditions was significantly reduced by Pal-RRLRARARARA. Under
      conditions of high shear, the velocity of platelets rolling on VWF was
      significantly increased when platelets are preincubated with Pal-RRLRARARARA.
      This study defines a novel function for the RRLRARARARA motif of GPIb beta in
      platelet activation.

PMID- 14675102
TI  - Human platelet glycoprotein VI function is antagonized by monoclonal antibody
      derived Fab fragments.
AB  - Platelet interactions with adhesive ligands exposed at sites of vascular injury
      initiate the normal hemostatic response but may also lead to arterial thrombosis.
      Platelet membrane glycoprotein (GP)VI is a key receptor for collagen. Impairment
      of GPVI function in mice results in a long-term antithrombotic protection and
      prevents neointimal hyperplasia following arterial injury. On the other hand,
      GPVI deficiency in humans or mice does not result in serious bleeding tendencies.
      Blocking GPVI function may thus represent a new and safe antithrombotic approach,
      but no specific, potent anti-GPVI directed at the human receptor is yet
      available. Our aim was to produce accessible antagonists of human GPVI to
      evaluate the consequences of GPVI blockade. Amongst several monoclonal antibodies
      to the extracellular domain of human GPVI, one, 9O12.2, was selected for its
      capacity to disrupt the interaction of GPVI with collagen in a purified system
      and to prevent the adhesion of cells expressing recombinant GPVI to collagen and
      collagen-related peptides (CRP). While 9O12.2 IgGs induced platelet activation by
      a mechanism involving GPVI and Fc gamma RIIA, 9O12.2 Fab fragments completely
      blocked collagen-induced platelet aggregation and secretion from 5 microg mL-1
      and fully prevented CRP-induced activation from 1.5 microg mL-1. 9O12.2 Fabs also
      inhibited the procoagulant activity of collagen-stimulated platelets and platelet
      adhesion to collagen in static conditions. Furthermore, 9O12.2 Fabs impaired
      platelet adhesion, and prevented thrombi formation under arterial flow
      conditions. We thus describe here for the first time a functional monoclonal
      antibody to human GPVI and demonstrate its effect on collagen-induced platelet
      aggregation and procoagulant activity, and on thrombus growth.

PMID- 14675103
TI  - The effect of the anorectic agent, d-fenfluramine, and its primary metabolite, d
      norfenfluramine, on intact human platelet serotonin uptake and efflux.
AB  - Dexfenfluramine, a drug formerly prescribed for treatment of obesity, caused
      heart valve damage and pulmonary hypertension in some people. The cause of the
      toxicity has not been defined, but 5-HT has been implicated. The objective of
      this study was to evaluate the effect of the anorectic agent, d-fenfluramine, and
      its major metabolite, d-norfenfluramine, on intact human platelet serotonin (5
      HT) transport in vitro. The effects of d-fenfluramine and d-norfenfluramine on
      platelet uptake and efflux of 3H-5-HT were measured in buffer at pH 6.7, to
      optimize serotonin transporter (SERT) function, and at pH 7.4. Uptake of 3H-5-HT
      at pH 6.7 and 7.4 was inhibited by both agents at micro m concentrations (IC50, d
      fenfluramine approximately 3 microM; d-norfenfluramine approximately 10 microM).
      However, no efflux of 3H-5-HT from labeled platelets at either pH 6.7 or 7.4
      occurred at similar concentrations of d-fenfluramine or d-norfenfluramine. With
      inhibition of platelet dense granule 3H-5-HT uptake by reserpine, efflux of 3H-5
      HT was observed at pH 6, but not at pH 7.4. Fluoxetine, a SERT inhibitor, was a
      more potent inhibitor of uptake (IC50 0.05 microM) than d-fenfluramine, but the
      anorectic agent, phentermine, had no effect. Therefore, d-fenfluramine and d
      norfenfluramine inhibit human platelet uptake of 5-HT in vitro at tissue
      concentrations attainable in vivo, but they do not stimulate 5-HT efflux due to
      dense granule sequestration. Inhibition of platelet 5-HT uptake may play a role
      in the cardiopulmonary toxicity of d-fenfluramine, but other factors probably
      contribute, since similar toxicity has not been observed with fluoxetine.

PMID- 14675104
TI  - Effect of mechanical ventilation on carotid artery thrombosis induced by
      photochemical injury in mice.
AB  - BACKGROUND: Increasing use of transgenic and gene targeting techniques for the
      investigation of hemostasis and vascular biology has generated interest in
      experimental models of carotid artery thrombosis in mice. OBJECTIVES: We tested
      the hypothesis that hypoventilation in anesthetized mice may cause hypercapnia,
      increased carotid artery blood flow, and altered thrombotic responses to
      photochemical injury of the carotid artery. METHODS: Arterial blood gases and
      carotid artery blood flow were measured in pentobarbital-anesthetized BALB/c or
      C57BL/6 J mice with and without mechanical ventilation. Photochemical injury of
      the carotid artery was induced using the rose bengal method. RESULTS: Compared
      with ventilated mice, unventilated mice had a 45% increase in carotid artery
      blood flow (0.74 +/- 0.04 vs. 0.41 +/- 0.03 mL min-1; P < 0.001) that was
      associated with an elevation of arterial PCO2 (58 +/- 4 vs. 33 +/- 4 mmHg; P <
      0.05) and a decrease in arterial pH (7.18 +/- 0.05 vs. 7.32 +/- 0.03; P < 0.05).
      Time to first occlusion of the carotid artery after photochemical injury was
      shorter in ventilated than in unventilated mice (29 +/- 6 vs. 73 +/- 9 min; P <
      0.001). Time to stable occlusion was also shorter in ventilated mice (49 +/- 8
      vs. 81 +/- 6 min; P < 0.05). Elevated carotid artery blood flow, hypercarbic
      acidosis, and prolonged occlusion times also were observed in mice ventilated
      with supplemental carbon dioxide. CONCLUSIONS: General anesthesia without
      mechanical ventilation has the potential to confound studies of experimental
      thrombosis in vivo by producing hypoventilation, hypercapnia, acidosis, and
      altered carotid artery blood flow. Mechanical ventilation with maintenance of
      normal blood gases may enhance the physiological insight gained from experimental
      models of carotid artery thrombosis in mice.

PMID- 14675105
TI  - Unusual expression of the F9 gene in peripheral lymphocytes hinders investigation
      of F9 mRNA in hemophilia B patients.

PMID- 14675106
TI  - High levels of fibrinogen are associated with the risk of deep venous thrombosis
      mainly in the elderly.

PMID- 14675107
TI  - Local endothelial function and leg symptoms in patients after deep vein
      thrombosis.

PMID- 14675108
TI  - A new rapid bedside assay for D-dimer measurement (Simplify D-dimer) in the
      diagnostic work-up for deep vein thrombosis.

PMID- 14675109
TI  - Rapid detection of the prothrombin C20209T variant by differential sensitivity to
      restriction endonuclease digestion.

PMID- 14675110
TI  - Eptifibatide-induced thrombocytopenia and circulating procoagulant platelet
      derived microparticles in a patient with acute coronary syndrome.

PMID- 14675111
TI  - The C-1T mutation in the annexin A5 Kozak sequence slightly increases the risk of
      myocardial infarction in men.

PMID- 14675112
TI  - Normal plasma mixing studies in the laboratory diagnosis of lupus anticoagulant.

PMID- 14675113
TI  - The effect of thalidomide on tissue factor activity in Mono Mac 6 cells and the
      relationship to tumor necrosis factor (TNF)-alpha-stimulated cells.

PMID- 14675114
TI  - Prevalence of factor XIII deficiency in patients presenting with a bleeding
      disorder in Pakistan.

PMID- 14675115
TI  - Heparin-releasable TFPI is not depleted after repeated injections of tinzaparin
      at therapeutic dose for up to 30 days.

PMID- 14675116
TI  - Successful treatment with dermatan sulfate in six patients with heparin-induced
      thrombocytopenia and acute venous thromboembolism.

PMID- 14675117
TI  - Selection bias largely explains the differential distribution of factor V Leiden
      in different patient populations between the centers--a rebuttal.

PMID- 14675118
TI  - Choice of replacement therapy for hemophilia-a rebuttal.

PMID- 14675120
TI  - Effect of prolonged sitting on thrombin generation: not evidenced yet: rebuttal.

PMID- 14675124
TI  - Regulation of antioxidant enzymes: a significant role for melatonin.
AB  - Antioxidant enzymes form the first line of defense against free radicals in
      organisms. Their regulation depends mainly on the oxidant status of the cell,
      given that oxidants are their principal modulators. However, other factors have
      been reported to increase antioxidant enzyme activity and/or gene expression.
      During the last decade, the antioxidant melatonin has been shown to possess
      genomic actions, regulating the expression of several genes. Melatonin also
      influences both antioxidant enzyme activity and cellular mRNA levels for these
      enzymes. In the present report, we review the studies which document the
      influence of melatonin on the activity and expression of the antioxidative
      enzymes glutathione peroxidase, superoxide dismutases and catalase both under
      physiological and under conditions of elevated oxidative stress. We also analyze
      the possible mechanisms by which melatonin regulates these enzymes.

PMID- 14675125
TI  - Melatonin prevents disruption of hepatic reactive oxygen species metabolism in
      rats treated with carbon tetrachloride.
AB  - We reported that melatonin prevents the progression of carbon tetrachloride
      (CCl4)-induced acute liver injury in rats possibly by attenuating enhanced lipid
      peroxidation and reduced glutathione depletion. Herein, we examined the effect of
      melatonin on the changes in hepatic reactive oxygen species (ROS) metabolism in
      rats with a single intraperitoneal injection of CCl4 (1.6 g/kg body weight); the
      intent was to clarify the therapeutic mechanism of the indoleamine on CCl4
      induced acute liver injury. Rats with and without CCl4 treatment received a
      single oral dose of melatonin (10, 50 or 100 mg/kg body weight) 6 hr after CCl4
      treatment. Hepatic concentrations of ascorbic acid (ASC) and vitamin E (VE) and
      hepatic activities of superoxide dismutase (SOD), catalase (CAT), Se-glutathione
      peroxidase (Se-GSH-Px), glutathione reductase (GSSG-R), glucose-6-phosphate
      dehydrogenase (G-6-PDH), and xanthine oxidase (XO) were determined 6 and 24 hr
      after CCl4 treatment. The liver of CCl4-treated rats showed reductions in ASC
      concentrations, and SOD activity and an increase in G-6-PDH activity at 6 hr
      after treatment and further decreases in ACS concentrations and SOD activity and
      also further increase in G-6-PDH activity in addition to decreases in CAT and
      GSSG-R activities and increases in VE concentrations and XO activity at 24 hr
      after treatment. Melatonin attenuated the reductions in hepatic ASC
      concentrations and SOD, CAT and GSSG-R activities and the increase in hepatic XO
      activity in a dose-dependent manner without affecting either hepatic Se-GSH-Px
      activity or the increased hepatic VE concentration and G-6-PDH activity at 24 hr
      after CCl4 treatment. No dose of melatonin influenced hepatic ACS and VE
      concentrations and SOD, CAT, Se-GSH-Px, G-6-PDH, and XO activities in CCl4
      untreated rats. These results indicate that melatonin postadministered at
      pharmacological doses prevents the disruption of hepatic ROS metabolism
      associated with ASC, SOD, CAT, GSSG-R, and XO, in addition to reduced
      glutathione, in CCl4-treated rats.

PMID- 14675126
TI  - Melatonin suppresses cerebral edema caused by middle cerebral artery
      occlusion/reperfusion in rats assessed by magnetic resonance imaging.
AB  - Melatonin, a pineal secretory product synthesized from tryptophan, has been found
      to be effective against neurotoxicity. The present study was aimed at
      demonstrating the effectiveness of melatonin in vivo in reducing ischemia-induced
      cerebral edema using magnetic resonance imaging (MRI). Rats were subjected to
      middle cerebral artery (MCA) occlusion/reperfusion surgery. Melatonin was
      administered twice (6.0 mg/kg, p.o.) just prior to 1 hr of MCA occlusion and 1
      day after the surgery. T2-weighted multislice spin-echo images were acquired 1
      day after the surgery. In the saline-treated control rats, increases in T2
      weighted signals (water content) were clearly observed in the striatum and in the
      cerebral cortex. In the melatonin-treated group, total volume of edema was
      reduced by 51.6% compared with control group (P < 0.01). The protective effect of
      melatonin against edema was more clearly observed in the cerebral cortex (reduced
      by 59.8%, P < 0.01) than in the striatum (reduced by 34.2%, P < 0.05). Edema
      volume in a coronal slice was the greatest at the level of the bregma.
      Suppression of cerebral edema by melatonin was more effective posterior than
      anterior to the bregma. Melatonin appeared to reduce the volume of the edematous
      sites rather than to shift the signal intensity distribution. The present MRI
      study clearly demonstrates the effectiveness of melatonin against cerebral edema
      formation in ischemic animals in vivo, especially in the cerebral cortex.
      Melatonin may be highly useful in preventing cortical dysfunctions such as motor,
      sensory, memory, and psychological impairments associated with ischemic stroke.

PMID- 14675127
TI  - Melatonin protects against oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine in the mouse nigrostriatum.
AB  - We tested the hypothesis that melatonin acts as a powerful hydroxyl radical (*OH)
      scavenger in vivo in the brain, and interferes with oxidative stress caused by
      the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
      We investigated the effect of melatonin on in vitro *OH production employing a
      Fenton-like reaction in test tubes, and ex vivo *OH generation in isolated
      mitochondria induced by 1-methyl-4-phenyl pyridinium (MPP+), as well as on in
      vivo *OH formation in the mouse striatum following systemic administration of
      MPTP. We also measured reduced glutathione (GSH) levels, and superoxide dismutase
      (SOD) activity in the nucleus caudatus putamen (NCP) and substantia nigra (SN), 7
      days following MPTP and/or melatonin administration. Melatonin caused a
      significant and dose-dependent inhibition of the production of *OH in the in
      vitro, ex vivo and in vivo experimental conditions. Melatonin caused no changes
      in monoamine oxidase-B activity, in vitro in mitochondrial P2 fractions or in
      vivo following systemic administration. MPTP treatment in mice caused a
      significant depletion of GSH, and increased the specific activity of SOD both in
      SN and NCP on the seventh day. MPTP-induced GSH depletion was dose-dependently
      blocked in SN and NCP by melatonin. Higher doses of melatonin exhibited a
      synergistic effect on MPTP-induced increase in the SOD activity in the SN. These
      results suggest that while GSH inhibition is a direct consequence of *OH
      generation following neurotoxin administration, the increase in SOD activity is a
      compensatory mechanism for removing superoxide radicals generated as the result
      of MPTP. Our results not only point to the potency of melatonin in blocking the
      primary insults caused by MPTP, but also provide evidence for triggering
      secondary neuroprotective mechanisms, suggesting its use as a therapeutic agent
      in neurodegenerative disorders, such as Parkinson's disease.

PMID- 14675128
TI  - Delayed treatment with melatonin enhances electrophysiological recovery following
      transient focal cerebral ischemia in rats.
AB  - Melatonin has been reported to reduce infarct volumes induced by transient middle
      cerebral artery (MCA) occlusion. We examined whether melatonin could improve
      electrophysiological and neurobehavioral recoveries in rats after 72 hr of
      reperfusion following 1.5 hr of MCA occlusion. Melatonin (5 mg/kg) or vehicle was
      given intravenously at the commencement of reperfusion. Neurobehavioral outcome
      was serially examined, and somatosensory evoked potentials (SSEP) were recorded
      prior to ischemia and at 72 hr after the onset of reperfusion. Brain infarction
      was assessed upon killing. Before ischemia-reperfusion, stable SSEP waveforms
      were consistently recorded after individual fore- or hindpaw stimulation. The
      amplitude between the first positive (P1) and the first negative (N1) peaks and
      the P1 latency did not differ significantly between controls and melatonin
      treated animals. At 72 hr of reperfusion, controls had severely depressant SSEPs
      recorded from ischemic fore- and hindpaw cortical fields, and the amplitudes
      decreased to 36 and 35% of baselines, respectively (P < 0.001). These animals
      also had transcallosal electrophysiological diaschisis in the SSEPs recorded at
      the contralateral hindpaw cortical field (P < 0.01). Relative to controls,
      melatonin-treated animals not only had significantly improved amplitudes of the
      SSEPs recorded from both ischemic fore- and hindpaw cortical fields, by 33 and
      37% of baselines, respectively (P < 0.001), but also exhibited diminished
      transcallosal electrophysiological diaschisis following ischemia-reperfusion. In
      addition, melatonin improved sensory and motor neurobehavioral outcomes by 40 and
      28%, respectively (P < 0.001), and reduced cortical and striatal infarct sizes by
      32 and 40%, respectively (P < 0.05). Thus, delayed intravenous administration
      with melatonin both enhances electrophysiological and neurobehavioral recoveries
      and reduces cortical and striatal infarct sizes after cerebral ischemia and
      reperfusion injury.

PMID- 14675129
TI  - The melatonin receptor subtype MT1 is expressed in human gallbladder epithelia.
AB  - Based on the fact that human bile and, particularly gallbladder bile, contains
      high physiological levels of the antioxidant melatonin, the aim of this study was
      to investigate whether the melatonin receptor MT1 is present in human
      gallbladder. Expression and localization of MT1 was assessed by RT-PCR, Western
      blotting and immunofluorescence analysis in gallbladder samples from patients
      with cholelithiasis and with advanced gallbladder carcinoma. Additionally, we
      monitored mRNA expression of the two key enzymes of melatonin synthesis, i.e.
      arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase
      (HIOMT). MT1 mRNA and protein were present in all cholelithiasis (n = 10) and
      gallbladder carcinoma (n = 5) samples. As indicated from RT-PCR and Western blot
      studies, MT1 is located in gallbladder epithelia. Epithelial expression was
      further proven by immunofluorescence staining of MT1 in paraffin-embedded
      cholelithiasis and gallbladder carcinoma sections. Analysis of AANAT and HIOMT
      mRNA expression showed that HIOMT mRNA is present in gallbladder. Surprisingly,
      AANAT was not detectable under conditions where it was found in a human colon
      specimen. The absence of AANAT suggests that in human gallbladder, HIOMT might be
      involved in the formation of 5-hydroxytryptamine products other than melatonin.
      In summary, our results provide the first evidence for the presence of MT1 in
      human gallbladder epithelia. Therefore, in addition to its profound antioxidative
      effects in the biliary system, melatonin might also act through MT1-mediated
      signal transduction pathways. Thereby, it might be involved in the regulation of
      gallbladder function.

PMID- 14675130
TI  - Melatonin attenuates rat carotid chemoreceptor response to hypercapnic acidosis.
AB  - Respiratory activity is under circadian modulation and the physiological
      mechanisms may involve the pineal secretory product, melatonin, and the carotid
      chemoreceptor. We hypothesized that melatonin modulates the carotid chemoreceptor
      response to hypercapnic acidosis. To determine whether the effect of melatonin on
      the chemoreceptor response to hypercapnic acidosis is mediated by melatonin
      receptors in the chemosensitive cells, cytosolic calcium ([Ca2+]i) was measured
      by spectrofluorometry in fura-2-loaded glomus cells dissociated from rat carotid
      bodies. Melatonin (0.01-10 nm) per se did not change the [Ca2+]i levels of the
      glomus cells but it concentration-dependently attenuated the peak [Ca2+]i
      response to hypercapnic acidosis in the glomus cells. In addition, the [Ca2+]i
      response was attenuated by 2-iodomelatonin, an agonist of melatonin receptors.
      The melatonin-induced attenuation of the [Ca2+]i response to hypercapnic acidosis
      was abolished by pretreatment with an non-selective mt1/MT2 antagonist,
      luzindole, and by MT2 antagonists, 4-phenyl-2-propionamidotetraline or DH97. In
      situ hybridization study with antisense mt1 and MT2 receptor mRNA oligonucleotide
      probes showed an expression of mt1 and MT2 receptors in the rat carotid body.
      Also, melatonin attenuated the carotid afferent response to hypercapnic acidosis
      in single- or pauci-fibers recorded from the sinus nerve in isolated carotid
      bodies superfused with bicarbonate-buffer saline. Results suggest that an
      activation of the melatonin receptors expressed in the glomus cells of the rat
      carotid body reduces the chemoreceptor response to hypercapnic acidosis. This
      modulation may play a physiological role in the influence of the circadian
      rhythms on the chemoreflex.

PMID- 14675131
TI  - Protective effect of melatonin on random pattern skin flap necrosis in
      pinealectomized rat.
AB  - Random pattern skin flaps are still widely used in plastic surgery. However,
      necrosis in the distal portion resulting from ischemia is a serious problem,
      increasing the cost of treatment and hospitalization. Free oxygen radicals and
      increased neutrophil accumulation play an important role in tissue injury and may
      lead to partial or complete flap necrosis. To enhance skin flap viability, a
      variety of pharmacological agents have been intensively investigated. The aim of
      this study is to test the effects of melatonin, the chief secretory product of
      the pineal gland and a highly effective antioxidant, on random pattern skin flap
      survival in rats. Herein, to investigate the physiological and pharmacological
      role of melatonin on dorsal skin flap survival. Pharmacological (0.4, 4 and 40
      mg/kg) levels of melatonin were given intraperitoneally (i.p.). For this,
      pinealectomized (Px) and sham operated (non-Px) rats were used. The effects of
      melatonin on levels of malondialdehyde (MDA), nitric oxide (NO), glutathione
      (GSH) and the activities of glutathione peroxidase (GSH-Px) and superoxide
      dismutase (SOD) were measured in the skin flap. The ratio of skin flap necrosis
      was compared among the experimental groups by using planimetry. MDA and NO levels
      were found to be higher in Px than non-Px rats; while GSH levels and GSH-Px, and
      SOD activities were reduced. Melatonin administration to Px rats reduced MDA and
      NO levels and increased GSH, GSH-Px, SOD levels. Melatonin also reduced the ratio
      of flap necrosis determined by using planimetry and supported through the
      photography. In conclusion, these results show that both physiological and
      pharmacological concentrations of melatonin improve skin flap viability.

PMID- 14675132
TI  - Synthesis of internal labeled standards of melatonin and its metabolite N1-acetyl
      N2-formyl-5-methoxykynuramine for their quantification using an on-line liquid
      chromatography-electrospray tandem mass spectrometry system.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) is implicated in physiologic changes
      related to light-dark cycles and has been recently found to display antioxidant
      properties. It is known that the reaction of melatonin with certain reactive
      oxygen and nitrogen species, such as hydrogen peroxide and singlet oxygen,
      produces N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK). We report herein on the
      development of a new liquid chromatography/tandem mass spectrometry (LC/ESI/MS
      MS) assay to quantitatively determine melatonin and AFMK. The stable isotopic
      internal standard of melatonin-D3 was synthesized by the reaction of 5
      methoxytryptamine with deuterated acetyl chloride (CD3COCl). Labeled AFMK (AFMK
      D3) was obtained after photooxidation of melatonin-D3. The predominant ion [M +
      H]+ in the full scan mass spectra of melatonin, melatonin-D3, AFMK and AFMK-D3
      were located, respectively, at m/z = 233, 236, 265 and 268. The collision-induced
      dissociation of the molecules revealed a predominant fragment at m/z = 174 for
      melatonin and melatonin-D3 (loss of the N-acetyl group), and at m/z = 178 for
      AFMK and AFMK-D3 (loss of both the N-acetyl and the N-formyl groups). The m/z
      transitions from 233 to 174 (melatonin), from 236 to 174 (melatonin-D3), from 265
      to 178 (AFMK), and from 268 to 178 (AFMK-D3) were therefore chosen for the
      multiple reaction monitoring detection experiments, ensuring a high specificity
      and an accurate quantification of melatonin and AFMK in human plasma.

PMID- 14675133
TI  - Polymorphism of the MICA gene and risk for oral submucous fibrosis.
AB  - BACKGROUND: Oral submucous fibrosis (OSF), an insidious, pre-cancerous, chronic
      disease that may affect the entire oral cavity and sometimes extend to the
      pharynx has been reported to be associated with immune function. The major
      histocompatibility complex (MHC) class I chain-related gene A (MICA) is expressed
      by keratinocytes and other epithelial cells, and its encoded protein interacts
      with gamma/delta T-cells localized in the submucosa. The MICA gene has a triplet
      repeat (GCT) polymorphism in the transmembrane domain resulting in five distinct
      allelic patterns. METHODS: We analyzed MICA polymorphism in 80 OSF patients and
      351 randomly selected unrelated controls by using the ABI Prism 377-18 DNA
      sequencer (Applied Biosystems) to analyze the sample DNA PCR products. The number
      of microsatellite repeats was estimated with Genescan 672 software (Applied
      Biosystems) with a standard size marker of GS-350 TAMRA. RESULTS: The phenotype
      frequency of allele A6 of MICA in subjects with OSF was significantly higher than
      that in controls (OR = 3.48; 95% CI = 1.8-6.71; P = 0.0002), as was the frequency
      of the allele (OR = 2.65; 95% CI = 1.44-4.86; P = 0.001). CONCLUSION: The results
      suggest that allele A6 in MICA might confer a risk for OSF.

PMID- 14675134
TI  - Cross-sectional study of oral mucosal conditions among a central Amazonian Indian
      community, Brazil.
AB  - BACKGROUND: A cross-sectional study on the oral mucosal conditions among the
      Waimiri Atroari Indians from central Amazonia, Brazil, has been conducted. These
      Indians keep their traditional way of life and are free from habits such as
      smoking, alcohol drinking, and use of pacifiers. METHODS: Clinical examinations
      of a representative, randomly selected sample of patients during routine dental
      treatment, following ethical procedures recommended by Brazilian laws were made.
      RESULTS: Out of 922 individuals, 587 were examined, among which 52.57% of the
      children up to 12 years old and 73.44% of patients aged 13 years or older
      presented at least one oral mucosal condition. The conditions more frequently
      observed were, in decreasing order of prevalence: fissured tongue, focal
      epithelial hyperplasia (FEH), lesions of traumatic origin, geographic tongue,
      Fordyce's spots, and candidiasis. Only one case of leukoplakia was identified.
      CONCLUSIONS: Conditions observed among theses Indians were essentially the same
      that have been described in other populations around the world, except for FEH,
      which, as a characteristic lesion of Indians, had high prevalence (20.95%). The
      lesions observed were related to the way of life of this specific population.

PMID- 14675135
TI  - Vascular endothelial growth factor (VEGF) and chronic graft-versus-host disease
      (cGVHD) in salivary glands of bone marrow transplant (BMT) recipients.
AB  - BACKGROUND: The purpose of this study was to compare the immunolocalization of
      vascular endothelial growth factor (VEGF) in salivary glands of bone marrow
      transplant (BMT) recipients with normal controls and between the different stages
      of chronic graft-versus-host disease (cGVHD). In addition, the impact of the
      immunolocalization of VEGF on the survival rate of BMT patients was investigated
      as well. METHODS: Labial salivary glands obtained at the day 100+ from 36
      consecutive patients, who underwent BMT, were included in the study. The
      streptavidin-biotin-peroxidase complex stain was used to detect VEGF in the
      salivary glands. Time of death after BMT was displayed by means of the Kaplan
      Meier method for the following parameters: age and gender of the patients, donor
      gender, acute GVHD, cGVHD staging at the labial salivary glands, primary disease,
      platelet and neutrophils counts on day of biopsy, stem cell, oral mucositis,
      parenteral nutrition, oral lichenoid lesions of GVHD, conditioning regimen and
      immunolocalization degree of VEGF in labial salivary glands. The data were
      initially analyzed by means of the log-rank test and then included in the Cox's
      proportional hazard model. RESULTS: No differences on the immunolocalization of
      VEGF in the labial salivary glands of BMT recipients and control group or between
      the different stages of glandular cGVHD were noted. Both univariate and
      multivariate analysis of the survival rate showed significance of 5% only for
      platelet count over 100 x 109/l on the day of biopsy and male donor gender.
      CONCLUSIONS: Platelet count over 100 x 109/l and male donor gender are positive
      predictive factors on the survival rate after BMT. In addition, the
      immunolocalization of VEGF in salivary glands is not altered in BMT recipients at
      day 100+ and is not influenced by the stage of cGVHD.

PMID- 14675136
TI  - Prevalence of oral mucosal alterations in children from 0 to 12 years old.
AB  - BACKGROUND: As the exact prevalence of oral alterations in children is still not
      known and the findings are controversial, other studies about this subject are
      necessary. METHODS: A cross-sectional survey was carried out on 1211 Brazilian
      children divided in two age groups: 0-4 and 5-12 years. The patients were
      economically classified and data of medical history were obtained from medical
      records. RESULTS: The frequency of children presenting alterations was 27.0%, and
      it was higher in older children. The most common lesions were geographic tongue,
      cheek biting, and melanotic macule. Candidiasis was associated with antibiotic
      therapy and use of pacifiers. Fissured tongue was associated with congenital
      anomalies, allergy; age from 5 to 12 years. There was a lack of association of
      patient's economic status and prevalence of oral mucosal alterations.
      CONCLUSIONS: The frequency of mucosal alterations in children is high and
      increases with age, and some of them are associated with habits and medical
      history of the patients.

PMID- 14675137
TI  - Cell death and cell proliferation in the regeneration of atrophied rat
      submandibular glands after duct ligation.
AB  - BACKGROUND: The present study aimed to clarify the proliferation and apoptosis of
      parenchymal cells during regeneration of rat submandibular glands following
      atrophy. METHODS: Atrophy of the right submandibular gland of rats was induced by
      excretory duct ligation at the hilum with metal clips, which were removed 1 week
      (day 0) after ligation. The right submandibular glands were collected from 0 to
      14 days after removal of the clips and investigated using immunohistochemistry
      for proliferating cell nuclear antigen (PCNA) as a marker of proliferating cells,
      terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end
      labeling (TUNEL) as a marker of apoptotic cells, and transmission electron
      microscopy (TEM). RESULTS: After 1 week of ligation, there were many remaining
      ducts and a few acini in the atrophic glands. At day 3 after discontinuing the
      ligation, newly formed acini appeared and thereafter increased in number and
      maturity. Many residual and newly formed acinar cells showed positive reaction to
      PCNA especially at days 4 and 5. The PCNA-positive duct cells decreased in number
      with the regeneration. A few TUNEL-positive acinar and duct cells were identified
      during regeneration. Mitosis and apoptosis of parenchymal cells were also
      identified by TEM. CONCLUSIONS: During regeneration of the submandibular gland
      after atrophy, both residual and newly formed acinar cells proliferate actively.
      There is also apoptosis of parenchymal cells; however, the significance of
      apoptosis is low.

PMID- 14675138
TI  - Co-expression of p53 and Ki67 and lack of EBV expression in oral squamous cell
      carcinoma.
AB  - BACKGROUND: The objectives of the study were to determine the association between
      Epstein-Barr virus (EBV) and oral squamous cell carcinoma (OSCC), to compare the
      expression of p53 and Ki67 between normal oral mucosa, oral hyperkeratosis, oral
      pre-malignant dysplasia, and OSCC, and to determine the correlation between the
      expression of p53 and Ki67 in OSCC. METHODS: The expression of EBV mRNA was
      studied by in situ hybridization technique in 24 cases of OSCC, and the
      expression of p53 and Ki67 was investigated by immunohistochemical method in 19
      cases of OSCC, 7 cases of oral pre-malignant dysplasia, 6 cases of oral
      hyperkeratosis, and 5 cases of normal oral epithelium. RESULTS: None of OSCC
      cases expressed EBV-encoded RNA (EBER) transcripts. The labeling indices (LI) of
      p53- and Ki67-positive cells were significantly higher in OSCC than in oral pre
      malignant dysplasia, oral hyperkeratosis, and normal oral mucosa (P < 0.05). A
      significant correlation between the LI of p53- and Ki67-positive cells was
      observed in OSCC (r = 0.6; P = 0.01). CONCLUSIONS: These findings suggested that
      the co-expression of p53 and Ki67 may play roles in carcinogenesis of OSCC and
      p53 overexpression may promote cell proliferation in OSCC. Furthermore, EBV does
      not appear to be a risk factor for OSCC particularly in the population of
      northern Thailand.

PMID- 14675139
TI  - MEK inhibition enhances bleomycin A5-induced apoptosis in an oral cancer cell
      line: signaling mechanisms and therapeutic opportunities.
AB  - BACKGROUND: Bleomycin A5 is an anti-neoplastic glycoprotein antibiotic used for
      the treatment of various cancers. Previous work has shown that bleomycin A5
      exerts its apoptotic effects on tumor cells. This was to study the signal
      transduction pathways that might exert the apoptotic effects of bleomycin A5 on
      tumor cells, as well as to examine the possibility of lower dosing of such drug
      in combinative treatment with other compounds in vitro. METHODS: Bleomycin A5 was
      applied on a human oral epidermoid carcinoma cell line, human oral epidermoid
      carcinoma (KB), and the apoptotic activity was determined by the presence of DNA
      fragmentation and 4,6-diamidino-2-phenylindole (DAPI) nuclear staining. The
      signal transduction pathway was measured through Western blotting and in vitro
      kinase assay. RESULTS: The apoptotic effect was associated with the sustained
      activation of c-Jun N-terminal kinases (JNK) and the inhibition of extracellular
      signal-regulated kinases1 (ERK1) and -2 activities, suggesting that JNK plays a
      positive role in the death process. ERK1 and -2 might exert a protection pathway
      from cell death. Here, it was determined that a combination treatment of
      bleomycin A5 and the MAP kinase-ERK kinase (MEK) inhibitor, PD98059, could lead
      to enhanced apoptosis. The activities of ERK1 and -2 are required for cell
      survival signaling using stable cell clones expressing MEK1. Upon bleomycin A5
      treatment, cells expressing MEK1 exhibited significant delays in the onset of
      apoptosis, where the presence of MEK1 inhibitor enhanced cell death. Moreover,
      the increased activity of ERK1 and -2 coincided with cell survival. The survival
      signals exerted by MEK1 most likely result from the activation of ERK1 and -2.
      CONCLUSIONS: The apoptosis enhancement through such combinative treatment in
      vitro has revealed new therapeutic opportunities and elucidated mechanisms
      contributing to the efficacy of existing anti-cancer treatments.

PMID- 14675140
TI  - Expression of parathyroid hormone-related protein (PTHrP), osteoclast
      differentiation factor (ODF)/receptor activator of nuclear factor-kappaB ligand
      (RANKL) and osteoclastogenesis inhibitory factor (OCIF)/osteoprotegerin (OPG) in
      ameloblastomas.
AB  - BACKGROUND: To clarify the roles of osteoclast regulatory factors in progression
      of odontogenic tumors, expression of parathyroid hormone-related protein (PTHrP),
      osteoclast differentiation factor (ODF)/receptor activator of nuclear factor
      kappaB ligand (RANKL), and osteoclastogenesis inhibitory factor
      (OCIF)/osteoprotegerin (OPG) were analyzed in ameloblastomas as well as tooth
      germs. METHODS: Tissue specimens of nine tooth germs and 36 benign and one
      malignant ameloblastomas were examined by reverse transcriptase-polymerase chain
      reaction (RT-PCR) and immunohistochemistry for the expression of PTHrP,
      ODF/RANKL, and OCIF/OPG. RESULTS: Expression of PTHrP, ODF/RANKL, and OCIF/OPG
      mRNA was detected in all tooth germ and ameloblastoma samples.
      Immunohistochemical reactivity for PTHrP was recognized in both normal and
      neoplastic odontogenic epithelial cells. In ameloblastomas, PTHrP reactivity in
      peripheral columnar or cuboidal cells was stronger than that in central
      polyhedral cells, and keratinizing cells showed increased PTHrP reactivity.
      ODF/RANKL and OCIF/OPG were expressed predominantly in mesenchymal cells rather
      than in odontogenic epithelial cells in both tooth germs and ameloblastomas.
      Epithelial ODF/RANKL and OCIF/OPG expression was slightly lower in ameloblastomas
      than in tooth germs. Tumor cells in plexiform ameloblastomas showed slightly
      higher reactivity for PTHrP and ODF/RANKL than tumor cells in follicular
      ameloblastomas. CONCLUSION: Expression of PTHrP, ODF/RANKL and OCIF/OPG in tooth
      germs and ameloblastomas suggests that these factors might locally regulate bone
      metabolism and dynamics in tooth development as well as in progression of
      ameloblastomas. These factors might also be involved in tumor cell
      differentiation and/or tumor tissue structuring in ameloblastomas.

PMID- 14675141
TI  - Myxolipomatous pleomorphic adenoma: an unusual oral presentation.
AB  - The first case of a myxoid variant of lipomatous pleomorphic adenoma arising in
      the intraoral minor salivary gland is presented. A well-encapsulated tumor was
      composed almost entirely of myxolipomatous tissue with honeycomb-like spindled
      cellular areas, which contained only a scant glandular element.
      Immunohistochemistry confirmed the myoepithelial nature of spindle cells
      intimately admixed with mucoadipose component. We propose the term myxolipomatous
      pleomorphic adenoma for this peculiar lesion.

PMID- 14675142
TI  - Amiodarone-induced peri-oral photosensitivity.
AB  - We describe a 70-year-old Caucasian man with recurrent history of blistering of
      peri-oral skin during summer months. Following the diagnosis of a phototoxic
      reaction to Amiodarone, this was discontinued and an alternative drug to control
      his cardiac arrhythmia was prescribed. His peri-oral lesions rapidly resolved,
      and there has been no further recurrence. A brief review on photosensitivity and
      the underlying mechanisms are discussed.

PMID- 14675143
TI  - Mucinous adenocarcinoma with neuroendocrine differentiation of the mandibular
      ramus: report of a case.
AB  - A rare case of mucinous adenocarcinoma with neuroendocrine differentiation of the
      mandibular ramus is presented. The patient, an 80-year-old man, was referred to
      our hospital with chief complaint of swelling and pain in the left buccal mucosa.
      CT and MRI examination showed an osteolytic tumor mass occupying the upper region
      of the left mandibular ramus. Macroscopically, the excised tumor was a relatively
      well-defined, solid mass with diffuse bone resorption, measuring 3 cm x 3.2 cm x
      3 cm. Microscopical examination showed that the tumor forming glandular
      structures with abundant mucous production and high cellular atypia.
      Immunohistochemical studies demonstrated the positive reactivities for pan
      keratin, cytokeratin 7, vimentin,alpha-amylase, alpha-smooth muscle actin, neuron
      specific enolase, glial fibrillary acid protein, calcitonin, and somatostatin in
      tumor cells. These findings suggested that the tumor was originated from
      heterotopic or misplaced salivary gland in the mandible.

PMID- 14675144
TI  - Differential profile of CRF receptor distribution in the rat stomach and duodenum
      assessed by newly developed CRF receptor antibodies.
AB  - Peripheral corticotropin-releasing factor (CRF) receptor ligands inhibit gastric
      acid secretion and emptying while stimulating gastric mucosal blood flow in rats.
      Endogenous CRF ligands are expressed in the upper gastrointestinal (GI) tissues
      pointing to local expression of CRF receptors. We mapped the distribution of CRF
      receptor type 1 (CRF1) and 2 (CRF2) in the rat upper GI. Polyclonal antisera
      directed against the C-terminus of the CRF receptor protein were generated in
      rabbits and characterized by western blotting and immunofluorescence using CRF1-
      and CRF2-transfected cell lines and in primary cultured neurons from rat brain
      cortex. A selective anti-CRF1 antiserum (4467a-CRF1) was identified and used in
      parallel with another antiserum recognizing both CRF1 and CRF2 (4392a-CRF1&2) to
      immunostain gastric tissue sections. Antiserum 4467a-CRF1 demonstrated specific
      immunostaining in a narrow zone in the upper oxyntic gland within the stomach
      corpus. Conversely, 4392a-CRF1&2 labeled cells throughout the oxyntic gland and
      submucosal blood vessels. Pre-absorption with the specific antigen peptide
      blocked immunostaining in all experiments. Doublestaining showed co-localization
      of 4392a-CRF1&2 but not 4467a-CRF1 immunoreactivity with H/K-ATPase and
      somatostatin immunostaining in parietal and endocrine cells of the oxyntic gland.
      No specific staining was observed in the antrum with either antisera, whereas
      only antiserum 4392a-CRF1&2 showed modest immunoreactivity in the duodenal
      mucosa. Finally, co-localization of CRF2 and urocortin immunoreactivity was found
      in the gastric glands. These results indicate that both CRF receptor subtypes are
      expressed in the rat upper GI tissues with a distinct pattern and regional
      differences suggesting differential function.

PMID- 14675145
TI  - Delayed but sustained induction of mitogen-activated protein kinase activity is
      associated with beta-adrenergic receptor-mediated morphological differentiation
      of astrocytes.
AB  - Astroglial beta-adrenergic receptors (beta-ARs) are functionally linked to
      regulate cellular morphology. In primary cultures, the beta-AR agonist
      isoproterenol (ISP) can transform flat polygonal astrocytes into process-bearing,
      mature stellate cells by 48 h, an effect that can be blocked by the beta-AR
      antagonist, propranolol. ISP induced immediate activation of protein kinase A
      (PKA) which persisted up to 2 h, with no visible change in cell morphology.
      However, activation of PKA was sufficient to drive the process of transformation
      to completion, suggesting the involvement of downstream regulators of PKA. In
      addition to PKA inhibitors, the mitogen-activated protein kinase (MAPK) kinase
      inhibitor PD098059 also blocked ISP-induced morphological transformation. ISP
      treatment resulted in a biphasic response of cellular phosphorylated MAPK
      (phosphorylated extracellular signal-regulated kinase; p-ERK) level: an initial
      decline in p-ERK level followed by a sustained induction at 12-24 h, both of
      which were blocked by PKA inhibitor. The induction in pERK level coincided with
      initiation of morphological differentiation of the astrocytes and nuclear
      translocation of p-ERK. A long-lasting activation of p-ERK activity by ISP, at a
      later stage, appears to be critical for the transformation of astrocytes.

PMID- 14675146
TI  - Puromycin selectively increases mdr1a expression in immortalized rat brain
      endothelial cell lines.
AB  - The blood-brain barrier (BBB) plays an important role in controlling the passage
      of molecules from blood to brain extracellular fluid. The multidrug efflux pump P
      glycoprotein (P-gp) is highly expressed in the luminal membrane of brain
      endothelium and contributes to the formation of a functional barrier to lipid
      soluble drugs such as anticancer agents. The mdr1a P-gp-encoding gene is
      exclusively expressed in the rodent BBB. Primary cultures of rat brain
      endothelial cells and GP8.3 cells showed a dramatic decrease in mdr1a mRNA level
      and some expression of mdr1b mRNA. GPNT cells, derived from GP8.3 cells after
      transfection with a puromycin resistance gene, were chronically treated with 5
      microg/mL puromycin, a P-gp substrate. Compared with rat brain endothelial cells
      and GP8.3 cells, GPNT cells exhibited a very high level of expression of mdr1a
      mRNA together with a moderate level of mdr1b mRNA expression. Accordingly, P-gp
      expression and activity were strongly increased. When GP8.3 and puromycin-starved
      GPNT cells were treated with puromycin, mdr1a expression was selectively
      increased. High expression of mdr1a mRNA in GPNT cells may thus be related to the
      chronic treatment with puromycin. We conclude that GPNT cells may be used as a
      valuable rat in vitro model for studying the regulation of mdr1a expression at
      the BBB level.

PMID- 14675147
TI  - Glycogen in the brain of Drosophila melanogaster: diurnal rhythm and the effect
      of rest deprivation.
AB  - One function of sleep is thought to be the restoration of energy stores in the
      brain depleted during wakefulness. One such energy store found in mammalian
      brains is glycogen. Many of the genes involved in glycogen regulation in mammals
      have also been found in Drosophila melanogaster and rest behavior in Drosophila
      has recently been shown to have the characteristics of sleep. We therefore
      examined, in the fly, variation in the glycogen contents of the brain, the whole
      head and the body throughout the rest/activity cycle and after rest deprivation.
      Glycogen in the brain varies significantly throughout the day (p=0.001) and is
      highest during rest and lowest while flies are active. Glycogen levels in the
      whole head and body do not show diurnal variation. Brain glycogen drops
      significantly when flies are rest deprived for 3 h (p=0.034) but no significant
      differences are observed after 6 h of rest deprivation. In contrast, glycogen is
      significantly depleted in the body after both 3 and 6 h of rest deprivation
      (p<0.0001 and p<0.0001, respectively). Glycogen in the fly brain changes in
      relationship to rest and activity and demonstrates a biphasic response to rest
      deprivation similar to that observed in mammalian astrocytes in culture.

PMID- 14675148
TI  - Different effects of five dopamine receptor subtypes on nuclear factor-kappaB
      activity in NG108-15 cells and mouse brain.
AB  - We previously showed that dopamine receptors D1R and D2R expressed in NG108-15
      cells activated protein kinase A and extracellular signal-regulated kinase (ERK)
      respectively, resulting in differential activation of nuclear factor (NF)-kappaB
      activity. To investigate whether other dopamine receptor subtypes regulate NF
      kappaB, we established NG108-15 cells stably expressing D3R, D4R and D5R (NGD3R,
      NGD4R and NGD5R). D5R stimulation with SKF 38393 decreased NF-kappaB luciferase
      reporter activity in NGD5R cells, similar to D1R stimulation in NGD1R cells.
      However, D3R or D4R stimulation with quinpirole showed no change in NF-kappaB
      Luci activity, although forskolin-induced cyclic AMP responsive element-Luci
      activation was attenuated by quinpirole treatment in NGD2LR, NGD3R and NGD4R
      cells. As expected, activation of ERK or serum responsive element-luciferase
      reporter not observed following stimulation with quinpirole in D3R- or D4R
      expressing cells. We further examined the effects of haloperidol and risperidone,
      which are typical and atypical antipsychotic drugs respectively, on NF-kappaB
      activity by gel shift assay in mouse frontal cortex. Haloperidol treatment
      slightly attenuated basal NF-kappaB activity. By contrast, risperidone treatment
      enhanced NF-kappaB activity. Taken together, D2R and D1R/D5R had opposite effects
      on NF-kappaB activity in NG108-15 cells. Risperidone up-regulated and haloperidol
      down-regulated NF-kappaB activity in mouse brain. This effect may be related to
      the atypical antipsychotic properties of risperidone.

PMID- 14675149
TI  - Cyclin-dependent kinase 11p110 and casein kinase 2 (CK2) inhibit the interaction
      between tyrosine hydroxylase and 14-3-3.
AB  - Tyrosine hydroxylase (TH) is regulated by the reversible phosphorylation of
      serines 8, 19, 31 and 40. Upon initiation of this study, serine 19 was unique due
      to its requirement of 14-3-3 binding after phosphorylation for optimal enzyme
      activity, although it has been more recently demonstrated that phosphorylated
      serine 40 also binds 14-3-3. To identify proteins that interact with TH following
      phosphorylation of serine 19, this amino acid was mutated to alanine and THS19A
      was used as bait in a yeast two-hybrid system. From this, mouse-derived cyclin
      dependent kinase 11 (CDK11)p110 was identified as an interacting partner with
      THS19A. The interaction was confirmed using human CDK11p110 cDNA in a mammalian
      system. Previous research has demonstrated that casein kinase 2 (CK2) interacts
      with CDK11p110, and both were observed to phosphorylate TH in vitro. In addition,
      CDK11p110 overexpression was observed to inhibit the interaction between TH and
      14-3-3. A mechanism contributing to disruption of the interaction between TH and
      14-3-3 may be due to CK2 phosphorylation of specific 14-3-3 isoforms, i.e. 14-3-3
      tau. Collectively, these results imply that CDK11p110 and CK2 negatively regulate
      TH catecholamine biosynthetic activity since phosphoserine 19 of TH requires 14-3
      3 binding for optimal enzyme activity and a decreased rate of dephosphorylation.

PMID- 14675150
TI  - Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and
      striatal neurodegeneration in rats: possible relevance for atypical parkinsonism
      in Guadeloupe.
AB  - In Guadeloupe, epidemiological data have linked atypical parkinsonism with fruit
      and herbal teas from plants of the Annonaceae family, particularly Annona
      muricata. These plants contain a class of powerful, lipophilic complex I
      inhibitors, the annonaceous acetogenins. To determine the neurotoxic potential of
      these substances, we administered annonacin, the major acetogenin of A. muricata,
      to rats intravenously with Azlet osmotic minipumps (3.8 and 7.6 mg per kg per day
      for 28 days). Annonacin inhibited complex I in brain homogenates in a
      concentration-dependent manner, and, when administered systemically, entered the
      brain parenchyma, where it was detected by matrix-associated laser desorption
      ionization-time of flight mass spectrometry, and decreased brain ATP levels by
      44%. In the absence of evident systemic toxicity, we observed neuropathological
      abnormalities in the basal ganglia and brainstem nuclei. Stereological cell
      counts showed significant loss of dopaminergic neurones in the substantia nigra (
      31.7%), and cholinergic (-37.9%) and dopamine and cyclic AMP-regulated
      phosphoprotein (DARPP-32)-immunoreactive GABAergic neurones (-39.3%) in the
      striatum, accompanied by a significant increase in the number of astrocytes
      (35.4%) and microglial cells (73.4%). The distribution of the lesions was similar
      to that in patients with atypical parkinsonism. These data are compatible with
      the theory that annonaceous acetogenins, such as annonacin, might be implicated
      in the aetiology of Guadeloupean parkinsonism and support the hypothesis that
      some forms of parkinsonism might be induced by environmental toxins.

PMID- 14675151
TI  - Transcription of the M1 muscarinic receptor gene in neurons and neuronal
      progenitors of the embryonic rat forebrain.
AB  - Development of the nervous system is accompanied by expansion and differentiation
      of the neuronal progenitors within the embryonic neuroepithelium. Although the
      role of growth factors in this process is well documented, there is increasing
      evidence for a role of neurotransmitters. Acetylcholine is known to exert many
      actions on developing neural cells, but its potential role in neurogenesis is
      unclear. Here, we show that the M1 muscarinic acetylcholine receptor is expressed
      in the neuroepithelium of the rat forebrain, where it is found on both nestin+
      progenitor cells and TuJ1+ newly differentiated neurons. Furthermore,
      transcription is governed, at least in part, by regulatory cis elements that are
      also responsible for driving transcription in neuroblastoma cells. This
      represents the first demonstration of M1 receptors on neuronal progenitor cells
      and supports the notion that M1 muscarinic receptors may play a role in
      development of the nervous system prior to the onset of synaptogenesis and their
      subsequent role in neurotransmission.

PMID- 14675152
TI  - Increased expression and processing of caspase-12 after traumatic brain injury in
      rats.
AB  - Traumatic brain injury (TBI) disrupts tissue homeostasis resulting in
      pathological apoptotic activation. Recently, caspase-12 was reported to be
      induced and activated by the unfolded protein response following excess
      endoplasmic reticulum (ER) stress. This study examined rat caspase-12 expression
      using the controlled cortical impact TBI model. Immunoblots of fractionalized
      cell lysates found elevated caspase-12 proform (approximately 60 kDa) and
      processed form (approximately 12 kDa), with peak induction observed within 24 h
      post-injury in the cortex (418% and 503%, respectively). Hippocampus caspase-12
      proform induction peaked at 24 h post-injury (641%), while processed form
      induction peaked at 6 h (620%). Semi-quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis confirmed elevated caspase-12 mRNA
      levels after TBI. Injury severity (1.0, 1.2 or 1.6 mm compression) was associated
      with increased caspase-12 mRNA expression, peaking at 5 days in the cortex (657%,
      651% and 1259%, respectively) and 6 h in the hippocampus (435%, 451% and 460%,
      respectively). Immunohistochemical analysis revealed caspase-12 induction in
      neurons in both the cortex and hippocampus as well as in astrocytes at the
      contusion site. This is the first report of increased expression of caspase-12
      following TBI. Our results suggest that the caspase-12-mediated ER apoptotic
      pathway may play a role in rat TBI pathology independent of the receptor- or
      mitochondria-mediated apoptotic pathways.

PMID- 14675153
TI  - Long-term alterations in glutamate receptor and transporter expression following
      early-life seizures are associated with increased seizure susceptibility.
AB  - Prolonged seizures in early childhood are associated with an increased risk of
      development of epilepsy in later life. The mechanism(s) behind this
      susceptibility to later development of epilepsy is unclear. Increased synaptic
      activity during development has been shown to permanently alter excitatory
      neurotransmission and could be one of the mechanisms involved in this increased
      susceptibility to the development of epilepsy. In the present study we determine
      the effect of status-epilepticus induced by lithium/pilocarpine at postnatal day
      10 (P10 SE) on the expression of glutamate receptor and transporter mRNAs in
      hippocampal dentate granule cells and protein levels in dentate gyrus of these
      animals in adulthood. The results revealed a decrease in glutamate receptor 2
      (GluR2) mRNA expression and protein levels as well as an increase in protein
      levels for the excitatory amino acid carrier 1 (EAAC1) in P10 SE rats compared to
      controls. Expression of glutamate receptor 1 (GluR1) mRNA was decreased in both
      P10 SE rats and identically handled, lithium-injected littermate controls
      compared to naive animals, and GluR1 protein levels were significantly lower in
      lithium-controls than in naive rats, suggesting an effect of either the handling
      or the lithium on GluR1 expression. These changes in EAA receptors and
      transporters were accompanied by an increased susceptibility to kainic acid
      induced seizures in P10 SE rats compared to controls. The current data suggest
      that early-life status-epilepticus can result in permanent alterations in
      glutamate receptor and transporter gene expression, which may contribute to a
      lower seizure threshold.

PMID- 14675154
TI  - The voltage-gated calcium channel UNC-2 is involved in stress-mediated regulation
      of tryptophan hydroxylase.
AB  - Migraine is an episodic pain disorder whose pathophysiology is related to
      deficiency of serotonin signaling and abnormal function of the P/Q-type calcium
      channel, CACNA1A. Because the relationship of the CACNA1A channel to serotonin
      signaling is unknown and potentially of therapeutic interest we have used genetic
      analysis of the Caenorhabditis elegans ortholog of this calcium channel, UNC-2,
      to help identify candidate downstream effectors of the human channel. By genetic
      dissection of the lethargic mutant phenotype of unc-2, we have established an
      epistasis pathway showing that UNC-2 function antagonizes a transforming growth
      factor (TGF)-beta pathway influencing movement rate. This same UNC-2/TGF-beta
      pathway is required for accumulation of normal serotonin levels and stress
      induced modulation of tryptophan hydroxylase (tph) expression in the serotonergic
      chemosensory ADF neurons, but not the NSM neurons. We also show that transgenic
      expression of the migraine-associated Ca2+ channel, CACNA1A, in unc-2 animals can
      functionally substitute for UNC-2 in stress-activated regulation of tph
      expression. The demonstration that these evolutionarily related channels share a
      conserved ability to modulate tph expression through their effects on TGF-beta
      signaling provides the first specific example of how CACNA1A function may
      influence levels of the critical migraine neurotransmitter serotonin.

PMID- 14675155
TI  - Methamphetamine produces neuronal inclusions in the nigrostriatal system and in
      PC12 cells.
AB  - Mice treated with the psychostimulant methamphetamine (MA) showed the appearance
      of intracellular inclusions in the nucleus of medium sized striatal neurones and
      cytoplasm of neurones of the substantia nigra pars compacta but not in the
      frontal cortex. All inclusions contained ubiquitin, the ubiquitin activating
      enzyme (E1), the ubiquitin protein ligase (E3-like, parkin), low and high
      molecular weight heat shock proteins (HSP 40 and HSP 70). Inclusions found in
      nigral neurones stained for alpha-synuclein, a proteic hallmark of Lewy bodies
      that are frequently observed in Parkinson's disease and other degenerative
      disorders. However, differing from classic Lewy bodies, MA-induced neuronal
      inclusions appeared as multilamellar bodies resembling autophagic granules.
      Methamphetamine reproduced this effect in cultured PC12 cells, which offered the
      advantage of a simple cellular model for the study of the molecular determinants
      of neuronal inclusions. PC12 inclusions, similar to those observed in nigral
      neurones, were exclusively localized in the cytoplasm and stained for alpha
      synuclein. Time-dependent experiments showed that inclusions underwent a
      progressive fusion of the external membranes and developed an electrodense core.
      Inhibition of dopamine synthesis by alpha-methyl-p-tyrosine (alphaMpT), or
      administering the antioxidant S-apomorphine largely attenuated the formation of
      inclusions in PC12 cells exposed to MA. Inclusions were again observed when
      alphaMpT-treated cells were loaded with l-DOPA, which restored intracellular
      dopamine levels.

PMID- 14675156
TI  - Small peptides patterned after the N-terminus domain of SNAP25 inhibit SNARE
      complex assembly and regulated exocytosis.
AB  - Synthetic peptides patterned after the C-terminus of synaptosomal associated
      protein of 25 kDa (SNAP25) efficiently abrogate regulated exocytosis. In
      contrast, the use of SNAP25 N-terminal-derived peptides to modulate SNAP
      receptors (SNARE) complex assembly and neurosecretion has not been explored.
      Here, we show that the N-terminus of SNAP25, specially the segment that
      encompasses 22Ala-44Ile, is essential for the formation of the SNARE complex.
      Peptides patterned after this protein domain are potent inhibitors of SNARE
      complex formation. The inhibitory activity correlated with their propensity to
      adopt an alpha-helical secondary structure. These peptides abrogated SNARE
      complex formation only when added previous to the onset of aggregate assembly.
      Analysis of the mechanism of action revealed that these peptides disrupted the
      binary complex formed by SNAP25 and syntaxin. The identified peptides inhibited
      Ca2+-dependent exocytosis from detergent-permeabilized excitable cells.
      Noteworthy, these amino acid sequences markedly protected intact hippocampal
      neurones against hypoglycaemia-induced, glutamate-mediated excitotoxicity with a
      potency that rivalled that displayed by botulinum neurotoxins. Our findings
      indicate that peptides patterned after the N-terminus of SNAP25 are potent
      inhibitors of SNARE complex formation and neuronal exocytosis. Because of their
      activity in intact neurones, these cell permeable peptides may be hits for
      antispasmodic and analgesic drug development.

PMID- 14675157
TI  - Ischaemic preconditioning in the rat brain: effect on the activity of several
      initiation factors, Akt and extracellular signal-regulated protein kinase
      phosphorylation, and GRP78 and GADD34 expression.
AB  - Translational repression induced during reperfusion of the ischaemic brain is
      significantly attenuated by ischaemic preconditioning. The present work was
      undertaken to identify the components of the translational machinery involved and
      to determine whether translational attenuation selectively modifies protein
      expression patterns during reperfusion. Wistar rats were preconditioned by 5-min
      sublethal ischaemia and 2 days later, 30-min lethal ischaemia was induced.
      Several parameters were studied after lethal ischaemia and reperfusion in rats
      with and without acquired ischaemic tolerance (IT). The phosphorylation pattern
      of the alpha subunit of eukaryotic initiation factor 2 (eIF2) in rats with IT was
      exactly the same as in rats without IT, reaching a peak after 30 min reperfusion
      and returning to control values within 4 h in both the cortex and hippocampus.
      The levels of phosphorylated eIF4E-binding protein after lethal ischaemia and
      eIF4E at 30 min reperfusion were higher in rats with IT, notably in the
      hippocampus. eIF4G levels diminished slightly after ischaemia and reperfusion,
      paralleling calpain-mediated alpha-spectrin proteolysis in rats with and without
      IT, but they did not show any further decrease after 30 min reperfusion in rats
      with IT. The phosphorylated levels of eIF4G, phosphatidylinositol 3-kinase
      protein B (Akt) and extracellular signal-regulated kinases (ERKs) were very low
      after lethal ischaemia and increased following reperfusion. Ischaemic
      preconditioning did not modify the observed changes in eIF4G phosphorylation. All
      these results support that translation attenuation may occur through multiple
      targets. The levels of the glucose-regulated protein (78 kDa) remained unchanged
      in rats with and without IT. Conversely, our data establish a novel finding that
      ischaemia induces strong translation of growth arrest and DNA damage protein 34
      (GADD34) after 4 h of reperfusion. GADD34 protein was slightly up-regulated after
      preconditioning, besides, as in rats without IT, GADD34 levels underwent a
      further clear-cut increase during reperfusion, this time as earlier as 30 min and
      coincident with translation attenuation.

PMID- 14675158
TI  - Activation of brain prostanoid EP3 receptors via arachidonic acid cascade during
      behavioral suppression induced by Delta8-tetrahydrocannabinol.
AB  - We have previously shown that behavioral changes induced by cannabinoid were due
      to an elevation of prostaglandin E2 (PGE2) via the arachidonic acid cascade in
      the brain. In the present study, we investigated the participation of the
      prostanoid EP3 receptor, the target of PGE2 in the brain, in behavioral
      suppression induced by Delta8-tetrahydrocannabinol (Delta8-THC), an isomer of the
      naturally occurring Delta9-THC, using a one-lever operant task in rats.
      Intraperitoneal administration of Delta8-THC inhibited the lever-pressing
      behavior, which was significantly antagonized by both the selective cannabinoid
      CB1 receptor antagonist SR141716A and the cyclooxygenase inhibitor diclofenac.
      Furthermore, intracerebroventricular (i.c.v.) administration of PGE2
      significantly inhibited the lever-pressing performance similar to Delta8-THC.
      Prostanoid EP3 receptor antisense-oligodeoxynucleotide (AS-ODN; twice a day for 3
      days, i.c.v.) significantly decreased prostanoid EP3 receptor mRNA levels as
      determined by the RT-PCR analysis in the cerebral cortex, hippocampus and
      midbrain. AS-ODN also antagonized the PGE2-induced suppression of the lever
      pressing. In the same way, the suppression of lever-pressing behavior by Delta8
      THC was significantly improved by AS-ODN. It is concluded that the suppression of
      lever-pressing behavior by cannabinoid is due to activation of the prostanoid EP3
      receptor through an elevation of PGE2 in the brain.

PMID- 14675159
TI  - Enhanced detection and retrograde axonal transport of PrPc in peripheral nerve.
AB  - Neuroinvasion of the CNS during orally acquired transmissible spongiform
      encephalopathies (TSEs) may involve the transport of the infectious agent from
      the periphery to the CNS via the peripheral nerves. If this occurs within axons,
      the mechanism of axonal transport may be fundamental to the process. In studies
      of peripheral nerve we observed that the cellular prion protein (PrPc) is highly
      resistant to detergent extraction. The implication of this is an underestimation
      of the abundance of PrPc in peripheral nerve. We have developed nerve extraction
      conditions that enhance the quantification of the protein in nerve 16-fold.
      Application of these conditions to evaluate the accumulation of PrPc distal to a
      cut nerve now reveals that PrPc is retrogradely transported from the axon ending.
      These results provide a potential cellular mechanism for TSE infectivity to gain
      entry to the CNS from the periphery.

PMID- 14675160
TI  - The mechanism of membrane-translocation of regulator of G-protein signaling (RGS)
      8 induced by Galpha expression.
AB  - RGS (regulators of G-protein signaling) proteins comprise a large family that
      modulates heterotrimeric G-protein signaling. This protein family has a common
      RGS domain and functions as GTPase-activating proteins for the alpha-subunits of
      heterotrimeric G-proteins located at the plasma membrane. RGS8 was identified as
      a neuron-specific RGS protein, which belongs to the B/R4 subfamily. We previously
      showed that RGS8 protein was translocated to the plasma membrane from the nucleus
      on coexpression of GTPase-deficient Galphao (GalphaoQL). Here, we first examined
      which subtypes of Galpha can induce the translocation of RGS8. When the Galphai
      family was expressed, the translocation of RGS8 did occur. To investigate the
      mechanism of this translocation, we generated a mutant RGS8 with reduced affinity
      to Galphao and an RGS-insensitive (RGS-i) mutant of GalphaoQL. Co-expression
      experiments with both mutants revealed that disruption of the Galpha-RGS8
      interaction abolished the membrane-translocation of RGS8 despite the apparent
      membrane localization of RGS-i GalphaoQL. These results demonstrated that RGS8 is
      recruited to the plasma membrane where G-proteins are activated mainly by direct
      association with Galpha.

PMID- 14675161
TI  - Mitochondrial glutaminase enhances extracellular glutamate production in HIV-1
      infected macrophages: linkage to HIV-1 associated dementia.
AB  - Dysfunction in mononuclear phagocyte (MP, macrophages and microglia) immunity is
      thought to play a significant role in the pathogenesis of HIV-1 associated
      dementia (HAD). In particular, elevated extracellular concentrations of the
      excitatory neurotransmitter glutamate, produced by MP as a consequence of viral
      infection and immune activation, can induce neuronal injury. To determine the
      mechanism by which MP-mediated neuronal injury occurs, the concentration and
      rates of production of extracellular glutamate were measured in human monocyte
      derived macrophage (MDM) supernatants by reverse phase high-performance liquid
      chromatography (RP-HPLC). Measurements were taken of supernatants from MDM
      infected with multiple HIV-1 strains including ADA and DJV (macrophage tropic, M
      tropic), and 89.6 (dual tropic). High levels of glutamate were produced by MDM
      infected with M-tropic viruses. AZT, an inhibitor of HIV-1 replication, inhibited
      glutamate generation, demonstrating a linkage between HIV-1 infection and
      enhanced glutamate production. In our culture system, glutamate production was
      dependent upon the presence of glutamine and was inhibited by 6-diazo-5-oxo-L
      norleucine, a glutaminase inhibitor. Supernatants collected from HIV-1-infected
      MP generated more glutamate following glutamine addition than supernatants
      isolated from uninfected MP. These findings implicate the involvement of a
      glutamate-generating enzyme, such as phosphate-activated mitochondrial
      glutaminase (PMG) in MP-mediated glutamate production.

PMID- 14675162
TI  - Defined inflammatory states in astrocyte cultures: correlation with
      susceptibility towards CD95-driven apoptosis.
AB  - A complete cytokine mix (CCM) or its individual components tumour necrosis factor
      alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma)
      were used to switch resting murine astrocytes to reactive states. The
      transformation process was characterized by differential up-regulation of
      interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and inducible nitric oxide
      synthetase (iNOS) mRNA and protein and a subsequent release of prostaglandin E2,
      nitric oxide (NO) and IL-6. Both CD95L and anti-CD95 antibodies triggered caspase
      activation followed by apoptotic death in fully pro-inflammatory astrocytes,
      whereas resting cells were totally resistant. Two other death-inducing ligands,
      TNF and TNF-related apoptosis-inducing ligand (TRAIL) did not induce apoptosis in
      reactive astrocytes. The switch in astrocyte sensitivity was accompanied by up
      regulation of caspase-8 and CD95 as well as the capacity to recruit Fas
      associated death domain (FADD) to the activated death receptor complex. Neither
      CD95-mediated death, nor other inflammatory parameters were affected by
      inhibition of iNOS or COX, respectively. Accordingly, IFN-gamma was absolutely
      essential for up-regulation of iNOS, but not for the switch in apoptosis
      sensitivity. In contrast, p38 kinase activity was identified as an important
      controller of both the inflammatory reaction and apoptosis both in astrocytes
      stimulated with CCM and in glia exposed to TNF and IL-1 only.

PMID- 14675163
TI  - The mGlu2/3 receptor agonist, LY354740, blocks immobilization-induced increases
      in noradrenaline and dopamine release in the rat medial prefrontal cortex.
AB  - The metabotropic glutamate (mGlu2/3) receptor agonist, LY354740, exhibits
      anxiolytic-like properties in a number of rodent models. The present study
      utilized in vivo microdialysis to examine the effects of LY354740 on
      extracellular monoamine levels in the medial prefrontal cortex (mPFC) of animals
      subjected to 30 min immobilization stress. Immobilization stress significantly
      elevated extracellular levels of noradrenaline (NA) and dopamine (DA) in the
      mPFC, while systemic administration of LY354740 (30 mg/kg, s.c.) significantly
      attenuated immobilization-induced increases in both NA and DA. Reverse-dialysis
      of LY354740 (30 microm) into the mPFC significantly attenuated immobilization
      induced increases in NA, but not DA without affecting basal levels of either
      amine. In separate studies in the presence of citalopram (1 microm; reverse
      dialysis into the mPFC), systemic administration of LY354740 attenuated
      immobilization-induced increases in NA and DA, but had no effect on serotonin (5
      HT) levels. Co-administration of the selective mGlu2/3 receptor antagonist,
      LY341495, partially or fully reversed the attenuation in NA and DA levels
      produced by LY354740, respectively. Taken together, these data suggest that
      LY354740 may produce anti-stress actions, in part, by blocking stress-related
      increases in catecholamines in the mPFC via mGlu2/3 receptor stimulation.

PMID- 14675164
TI  - Role of proline residues in the expression and function of the human
      noradrenaline transporter.
AB  - The aim was to investigate the roles of proline residues in extracellular loop 2
      (P172, P183, P188 and P209) and transmembrane domains 2, 5, 11 and 12 (P108,
      P270, P526, P551, P552 and P570) in determining noradrenaline transporter (NET)
      expression and function. Mutants of human NET with these residues mutated to
      alanine were pharmacologically characterized. Mutation of P108, P270 and P526
      disrupted cell surface expression, from [3H]nisoxetine binding and confocal
      microscopy data. Mutations of P526, P551 and P570 reduced transporter turnover
      (Vmax of [3H]noradrenaline uptake/Bmax of [3H]nisoxetine binding) by 1.5-1.7-fold
      compared with wild-type NET, so these residues might be involved in
      conformational changes associated with substrate translocation. Conversely,
      mutations of P172, P183, P188 and P209 increased Vmax/Bmax by 2-3-fold compared
      with wild-type, indicating that the presence of these proline residues limits
      turnover of the NET. The mutations had few effects on apparent affinities of
      substrates or affinities of inhibitors, except decreases in inhibitor affinities
      after mutations of the P270 and P570 residues, and increases after mutation of
      the P526 residue. Hence, proline residues in extracellular loop 2 and in
      transmembrane domains have a range of roles in determining expression and
      function of the NET.

PMID- 14675165
TI  - Membrane properties of rat embryonic multipotent neural stem cells.
AB  - We have characterized several potential stem cell markers and defined the
      membrane properties of rat fetal (E10.5) neural stem cells (NSC) by
      immunocytochemistry, electrophysiology and microarray analysis.
      Immunocytochemical analysis demonstrates specificity of expression of Sox1,
      ABCG2/Bcrp1, and shows that nucleostemin labels both progenitor and stem cell
      populations. NSCs, like hematopoietic stem cells, express high levels of aldehyde
      dehydrogenase (ALDH) as assessed by Aldefluor labeling. Microarray analysis of 96
      transporters and channels showed that Glucose transporter 1 (Glut1/Slc2a1)
      expression is unique to fetal NSCs or other differentiated cells.
      Electrophysiological examination showed that fetal NSCs respond to acetylcholine
      and its agonists, such as nicotine and muscarine. NSCs express low levels of
      tetrodotoxin (TTX) sensitive and insensitive sodium channels and calcium channels
      while expressing at least three kinds of potassium channels. We find that gap
      junction communication is mediated by connexin (Cx)43 and Cx45, and is essential
      for NSC survival and proliferation. Overall, our results show that fetal NSCs
      exhibit a unique signature that can be used to determine their location and
      assess their ability to respond to their environment.

PMID- 14675166
TI  - Calpain-mediated proteolytic cleavage of the neuronal glycine transporter, GlyT2.
AB  - The glycine transporter 2 (GlyT2) belongs to the family of Na+/CL--dependent
      plasma membrane transporters and is localized on the presynaptic terminals of
      glycinergic neurons. GlyT2 differs from other family members by its extended N
      terminal cytoplasmic region. We report that activation of a Ca2+-dependent
      protease, most likely calpain, in spinal cord synaptosomes or cultured spinal
      cord neurons, results in partial proteolysis of GlyT2. Regions sensitive to
      calpain cleavage in vivo are located in the N-terminal and, to a lesser extent, C
      terminal regions of the transporter protein. Incubation of a GlyT2 N-terminal
      fusion protein with spinal cord extract in the presence of calcium followed by
      protein sequence analysis localized the major N-terminal cleavage site after
      methionine 156, with a second cleavage site being situated after glycine 164.
      Interestingly, the size of the N-terminally truncated GlyT2 protein (70 kDa) is
      similar to that of most other transporter family members, and truncated GlyT2
      displayed full transport activity upon expression in HEK293 cells. Our data
      suggest that Ca2+-triggered proteolysis may contribute to the regulation of GlyT2
      trafficking and/or function in the neuronal plasma membrane.

PMID- 14675167
TI  - The significance of the mutated divalent metal transporter (DMT1) on iron
      transport into the Belgrade rat brain.
AB  - Brain iron transport and distributional pattern of divalent metal transporter I
      (DMT1) were studied in homozygous Belgrade rats (b/b) which suffer from a
      mutation in the DMT1 gene. In adult rats, brain uptake of transferrin-bound iron
      injected intravenously (i.v.) was significantly lower compared with that in
      heterozygous Belgrade (+/b) and Wistar rats, whereas transferrin uptake was
      identical. The difference in iron uptake was not apparent until 30 min after
      injection. The brain iron concentration was lower, and neuronal transferrin
      receptor-immunoreactivity higher, in adult b/b rats, thus confirming their iron
      deficient stage. Antibodies targeting different sites on the DMT1 molecule
      consistently detected DMT1 in neurones and choroid plexus at the same level
      irrespective of strain, but failed to detect DMT1 in brain capillary endothelial
      cells (BCECs), or macro- or microglial cells. The absence of DMT1 in BCECs was
      confirmed in immunoblots of purified BCECs. DMT1 was virtually undetectable in
      neurones of rats aged 18 post-natal days irrespective of strain. Neuronal
      expression of transferrin receptors and DMT1 in adult rats implies that neurones
      at this age acquire iron by receptor-mediated endocytosis of transferrin followed
      by iron transport out of endosomes mediated by DMT1. The existence of the mutated
      DMT1 molecule in neurones suggests that the low cerebral iron uptake in b/b rats
      derives from a reduced neuronal uptake rather than an impaired iron transport
      through the blood-brain barrier.

PMID- 14675168
TI  - ATP-induced ATP release from astrocytes.
AB  - Propagation of interastrocyte Ca2+ waves is mediated by diffusion of
      extracellular adenosine triphosphate (ATP), and may require regenerative release
      of ATP. The ability of ATP to initiate release of intracellular ATP was assessed
      by labeling adenine nucleotide pools in astrocyte cultures with 14C-adenine. The
      14C-purines released during exposure to ATP were then identified by thin-layer
      chromatography. ATP treatment caused a five-fold increase in release of 14C-ATP
      but not 14C-ADP or 14C-AMP, indicating selectivity for release of ATP. Other P2
      receptor agonists also caused significant 14C-ATP release, and the P2 receptor
      antagonists suramin, reactive blue-2 and pyridoxalphosphate-6-azo(benzene-2,4
      disulfonic acid) (PPADS) inhibited ATP-induced 14C-ATP release to varying
      degrees, suggesting the involvement of a P2 receptor. ATP-induced 14C-ATP release
      was not affected by chelation of intracellular Ca2+ with BAPTA-AM, or by blockers
      of Ca2+ release from intracellular stores or of extracellular Ca2+ influx,
      suggesting a Ca2+-independent response. ATP-induced 14C-ATP release was
      significantly inhibited by non-selective anion channel blockers but not by
      blockers of ATP-binding cassette proteins, gap junction hemichannels, or
      vesicular exocytosis. Release of adenine nucleotides induced by 0 Ca2+ was, in
      contrast, not selective for ATP, and was susceptible to inhibition by gap
      junction blockers. These findings indicate that astrocytes are capable of ATP
      induced ATP release and support a role for regenerative ATP release in glial Ca2+
      wave propagation.

PMID- 14675169
TI  - Cultured peribulbar dermal sheath cells can induce hair follicle development and
      contribute to the dermal sheath and dermal papilla.
AB  - Green fluorescent protein (GFP)-expressing wild-type, and nontransgenic mouse
      vibrissa follicle cells were cultured and implanted to mouse ears and footpads.
      Dermal papiller (DP)-derived cells and cells from the peribulbar dermal sheath
      "cup" (DSC) induced new hair follicles in both implanted ears and footpads, while
      nonbulbar dermal sheath cells did not. Confocal microscopy revealed that GFP
      expressing DP and DSC cells induced hair growth associated with the formation of
      DP exclusively comprised of fluorescent cells. In mouse ears, but not footpads,
      fluorescent DP and DSC cells could also be identified in DP along with
      nonfluorescent cells. DSC cells were characterized in vivo and in vitro by low
      alkaline phosphatase activity in contrast to high alkaline phosphatase in DP
      cells. The results indicate transplanted DP and DSC cells were equally capable of
      DP formation and hair follicle induction. This suggests the DP and peribulbar DSC
      may be functionally similar. In addition to observing papillae exclusively
      composed of GFP-expressing cells, DP and DSC cells may also have combined with
      resident cells to form papillae composed of implanted GFP-expressing cells and
      host-derived non-GFP-expressing cells. Alkaline phosphatase expression may be
      utilized as a simple marker to identify hair follicle mesenchyme derived cells
      with hair follicle inductive abilities.

PMID- 14675170
TI  - Type II epithelial keratin 6hf (K6hf) is expressed in the companion layer,
      matrix, and medulla in anagen-stage hair follicles.
AB  - More than half of the known keratin genes (n approximately 50) are expressed in
      the hair follicle. An in-depth knowledge of their differential expression in this
      organ will help us to understand the mechanisms of its formation and cycling, and
      the etiology of inherited hair disorders. Keratin 6hf is a type II keratin
      recently shown to occur in the companion layer. We cloned the mouse ortholog and
      characterized its expression in skin and oral mucosa. The mK6hf gene is 9.1 kb
      long and located in the cluster of type II keratin genes on mouse chromosome 15,
      between the keratin 6 (mK6alpha/mK6beta) and hair keratin genes. In situ
      hybridization and protein immunolocalization showed that, in addition to the
      companion layer, mK6hf is expressed in the upper matrix and medulla of the anagen
      stage hair. This distribution is seen for all types of mouse hairs and medullated
      human hairs. The distribution of keratin 6hf protein in the hair shaft mirrors
      that of keratin 17, and the observation of reduced levels of keratin 6hf in
      keratin 17 null hair argues for a direct interaction between them. mK6hf is also
      expressed in the nail bed epithelium and fungiform papillae of dorsal tongue
      epithelium. Our findings provide an additional marker for the hair matrix and
      medulla, and suggest that the cellular precursors for the medulla, cortex, and
      cuticle compartments are already spatially segregated within the hair matrix.
      They also have obvious implications for the epithelial alterations associated
      with defects in keratin 6 genes.

PMID- 14675171
TI  - Inhibition of the transforming growth factor-beta/Smad signaling pathway in the
      epithelium of oral lichen.
AB  - The basal cells in epithelium of the erythematous form of oral lichen display
      hyperproliferation compared with normal oral mucosa. In this study we examined
      whether this is associated with disrupted production, activation, or signal
      transduction of the epithelial growth inhibitor transforming growth factor (TGF)
      beta1. In situ immunostaining showed that most epithelial cells in normal oral
      mucosa had nuclear and cytoplasmic Smad4 and phosphorylated Smad2/3, but
      expressed little or no Smad7. Expression of latency-associated peptide TGF-beta1,
      latent TGF-beta binding protein 1, TGF-beta type I receptor, and TGF-beta type II
      receptor was readily seen, but only very little TGF-beta1 was activated. In
      erythematous oral lichen, basal and lower spinous epithelial layers showed
      staining for latency-associated peptide TGF-beta1, TGF-beta type I receptor, and
      TGF-beta type II receptor. A band with scanty staining for these molecules, but
      with marked staining for active TGF-beta1, was seen in the upper spinous and
      granular layers. Numbers of epithelial cell nuclei with Smad4 and phosphorylated
      Smad2/3 staining were significantly reduced in erythematous oral lichen compared
      with normal oral mucosa. Basal and suprabasal cell layers in erythematous oral
      lichen showed strong cytoplasmic Smad7 protein staining, but in spinous and
      granular layers Smad7 was localized to the cell membrane. In situ hybridization
      showed strong Smad7 mRNA expression in almost all basal keratinocytes in
      erythematous oral lichen; by contrast, no or occasionally very weak Smad7 mRNA
      expression was seen in these cells in normal oral mucosa. The observations
      indicate that inhibition of the TGF-beta/Smad pathway may account for the
      hyperproliferation of keratinocytes in erythematous oral lichen.

PMID- 14675172
TI  - Cross-talk between RhoGTPases and stress activated kinases for matrix
      metalloproteinase-9 induction in response to keratinocytes injury.
AB  - Cell migration and extracellular matrix remodeling are two essential processes of
      wound healing, regulated by extracellular metalloproteinases such as matrix
      metalloproteinase-2 (Gelatinase A) and matrix metalloproteinase-9 (Gelatinase B).
      Expression of matrix metalloproteinase-9 is deregulated in numerous wound healing
      pathologies. To date the mechanisms regulating matrix metalloproteinase-9 during
      normal wound healing are poorly documented. Using both primary cultures of normal
      human keratinocytes and a wounding device especially designed to dissect the
      molecular events during the healing process in vitro, we show that matrix
      metalloproteinase-9 is stimulated by injury in normal human keratinocytes. This
      upregulation results from the mechanical stress created by injury and not from a
      soluble factor, secreted by wounded normal human keratinocytes. We also
      demonstrate that the Rho family of small GTPases, p38[MAPK] and JNK together play
      a key part in the signaling pathways controlling the stimulation of matrix
      metalloproteinase-9 in wounded cells. We provide lines of evidence indicating
      that in wounded keratinocytes, upregulation of matrix metalloproteinase-9 depends
      on two distinct pathways. The first involves Rac1 and/or Cdc42 that control the
      activation of p38[MAPK]. The second depends on RhoA activation that is required
      for stimulation of JNK.

PMID- 14675173
TI  - Perceptual matching for assessment of itch; reliability and responsiveness
      analyzed by a rank-invariant statistical method.
AB  - The aim of this study was to evaluate the reliability and responsiveness of a new
      device-perceptual matching by Matcher (Cefar Medical AB, Lund, Sweden)-in the
      assessment of the progress of experimentally induced itch as well as determine
      the reliability of the method in patients with skin disease and itch. The
      perceptual matching unit electrically stimulates the skin of the fingers in the
      left hand. When the amplitude of the sensation corresponded to that of the
      experienced itch, the subject was instructed to halt the stimulation and a value
      was automatically saved in the electronic device. A total of 36 healthy subjects
      and nine patients participated in the study. The healthy subjects were asked to
      rate the level of itch every 30 s during the first 5 min and thereafter every
      minute. The reliability was determined in a test-retest procedure of the time
      points 5, 10, and 15 min after induction of itching. To test the stability of the
      method, the first sensation of pain in healthy subjects without itch was
      determined every 10th minute during 60 min. In patients, the test-retest
      procedure was repeated within 5 min. Perceptual matching was found to be a
      reliable method of itch assessment, with no evidence for random individual
      disagreement between the assessments. The augmented rank order coefficient ra was
      excellent: 1.00 at 5 min; 0.99 at 10 min; and 1.00 at 15 min. There was a clear
      indication of responsiveness for detecting changes in itch over time, p<or=0.05.
      The perceptual matcher device can detect immediate changes in perceived itch and
      is also sensitive to gradual decreases after the induction of itch. The first
      sensation of pain in healthy subjects without itch was unaffected when assessed
      every 10th minute during 60 min. In patients, no evidence for random disagreement
      or systematic disagreement by group between repeated assessments was detected.
      The augmented rank order coefficient was high (0.98). In conclusion, Matcher
      measures itch intensity via perceptual matching with a high reliability and
      excellent responsiveness. The method is stable and can be recommended as an
      assessment tool for itch intensity both in experimental conditions as well as in
      patients with skin disease and itch.

PMID- 14675174
TI  - Epidermal overexpression of interleukin-19 and -20 mRNA in psoriatic skin
      disappears after short-term treatment with cyclosporine a or calcipotriol.
AB  - Interleukin-19, 20, and 24 are new members of the IL-10 family binding and
      signaling through the IL-20R1/IL-20R2 heterodimer, while IL-20 and 24 also bind
      to the IL-20R2/IL-22R1 heterodimer. Using in situ hybridization we have studied
      mRNA expression of IL-19, 20, and 24 and their related receptor chains in skin
      from psoriatic patients before and during short-term treatment with either oral
      cyclosporine A or topical calcipotriol. In untreated lesions IL-19 and IL-20 mRNA
      was expressed focally in epidermis above the dermal papillae, whereas IL-24 was
      expressed in mononuclear cells in the dermal infiltrate. The expression of IL-19
      and 20 mRNA was confined to the basal and suprabasal keratinocytes. No expression
      of IL-19 and 20 mRNA could be detected in uninvolved psoriatic skin. Treatment
      with cyclosporine A and calcipotriol resulted in disappearance of the IL-19 and
      20 mRNA. Expression of mRNA for the receptor chains IL-20R1 and IL-20R2 was found
      throughout the psoriatic epidermal layer, whereas IL-22R1 mRNA was predominantly
      expressed in the superficial part of the psoriatic epidermis. These findings show
      that IL-19 and IL-20 are synthesized by a distinct population of keratinocytes.
      It remains to be clarified whether IL-19 and IL-20 are implicated in the
      pathogenesis of psoriasis.

PMID- 14675175
TI  - Botulinum toxin type B blocks sudomotor function effectively: a 6 month follow
      up.
AB  - This study analyzes the suppression of sweat gland activity by botulinum toxin
      type B. We injected botulinum toxin type B (between 2 and 1000 mouse units
      subcutaneously) in the lateral side of both lower legs in 15 healthy volunteers.
      Sweat tests were carried out before botulinum toxin type B injections, and at 3
      wk, 3 mo, and 6 mo. We studied focal anhidrosis by iodine-starch staining and by
      capacitance hygrometry after carbachol iontophoresis, according to the
      quantitative sudomotor axon reflex test (QSART). Iodine starch staining indicated
      that a threshold dose of 8 mouse units botulinum toxin type B leads to anhidrotic
      skin spots (>4 cm2) after 3 wk. Duration of anhidrosis was prolonged for 3 mo
      when 15 mouse units and for 6 mo when 125 mouse units botulinum toxin type B were
      injected. The size of the anhidrotic area decreased with time (p<0.001),
      indicating partial recovery at the edges. After 3 wk, the QSART score had
      significantly decreased to 18% of baseline and had decreased to zero in most
      subjects with doses of 62.5 mouse units or more. After 3 mo, the QSART had
      returned to 91% of baseline in all but one subject and, after 6 mo, recovery of
      sudomotor function was complete. Analysis by iodine-starch staining and QSART
      indicated that botulinum toxin type B suppresses sudomotor function effectively,
      in a concentration-dependent manner.

PMID- 14675176
TI  - Collagen of chronically inflamed skin is over-modified and upregulates secretion
      of matrix metalloproteinase 2 and matrix-degrading enzymes by endothelial cells
      and fibroblasts.
AB  - In order to investigate the properties of collagen in chronically inflamed
      tissue, we isolated collagen from the ear skin of mice with chronic contact
      dermatitis and examined its biochemical characteristics and the functions that
      regulate the secretion of matrix metalloproteinase 2 and collagen-degrading
      enzymes from endothelial cells and fibroblasts. Collagen in skin with chronic
      contact dermatitis comprised 60% type I collagen and 40% type III collagen, which
      latter is higher than the content of type III collagen in control skin (35%). The
      denaturation temperature was higher (42 degrees C) than that of control skin (39
      degrees C). The alpha2 chain of type I collagen was over-hydroxylated at both
      proline and lysine residues. Segment-long-spacing crystallites of type I collagen
      were unusually connected in tandem. Collagen of chronically inflamed skin was
      less susceptible to matrix metalloproteinase 2 after heat denaturation.
      Endothelial cells and fibroblasts secreted an increased amount of matrix
      metalloproteinase 2 when cultured on a gel formed from the collagen of
      chronically inflamed skin. Collagen-degrading activity secreted from fibroblasts
      was also upregulated when cells were in contact with collagen of chronically
      inflamed skin. These results suggest that the collagen in chronically inflamed
      tissue has altered biochemical characteristics and functions, which may affect
      the pathogenesis of the chronic skin disease.

PMID- 14675177
TI  - Keratinocytes promote proliferation and inhibit apoptosis of the underlying
      fibroblasts: an important role in the pathogenesis of keloid.
AB  - Interactions between epidermal keratinocytes and dermal fibroblasts play an
      important role in regulating tissue homeostasis and repair. Nevertheless, little
      is known about the role of keratinocytes in the pathogenesis of keloid. In this
      study, we investigated the influence of normal skin- and keloid-derived
      keratinocytes on normal skin- and keloid-derived fibroblasts utilizing a serum
      free indirect coculture system. The keloid-derived fibroblasts showed a greater
      proliferation and minimal apoptosis when cocultured with normal skin- or keloid
      derived keratinocytes, and the results were most significant in the latter. This
      difference was not observed when the fibroblasts were treated with conditioned
      medium obtained from normal skin- and keloid-derived keratinocytes. Nevertheless,
      conditioned medium-treated groups showed more proliferation and less apoptosis
      compared to the nonconditioned medium-treated control groups. We also analyzed
      the profile of factors involved in cell growth and apoptosis in fibroblasts
      cocultured with keratinocytes. Extracellular signal-regulated kinase and c-Jun N
      terminal kinase phosphorylations and expression of Bcl-2 and transforming growth
      factor-beta1 were all significantly upregulated in the fibroblasts cocultured
      with keloid-derived keratinocytes. Together, these results strongly suggest that
      the overlying keratinocytes of the keloid lesion play an important role in
      keloidogenesis by promoting more proliferation and less apoptosis in the
      underlying fibroblasts through paracrine and double paracrine effects.

PMID- 14675178
TI  - Reversible dissociation of collagen in tissues.
AB  - The turbidity of most biologic tissues hinders the use of lasers for diagnostic
      and therapeutic purposes. Hyperosmotic agents such as glycerol have been used to
      alter the optical scattering properties of turbid tissues. The mechanism of this
      effect, "optical clearing", however, remains incompletely understood. Multiphoton
      microscopy utilizing second harmonic generation can be used to monitor collagen
      structural changes in the presence of glycerol. This study suggests that the use
      of glycerol for tissue "optical clearing" screens noncovalent intermolecular
      interactions between low-order collagen structures, resulting in fiber
      disassembly. Dissociation of collagen fibers in native and engineered tissues in
      the presence of glycerol and reassociation with the application of saline are
      imaged dynamically. Collagen fiber reassembly is governed by the displacement of
      glycerol by saline in native and engineered skin. These results reveal the
      assembly process of high-order collagen structures and propose a molecular
      mechanism for the increase in tissue transparency observed after glycerol
      application.

PMID- 14675179
TI  - Rapid decay of alpha6 integrin caused by a mis-sense mutation in the propeller
      domain results in severe junctional epidermolysis bullosa with pyloric atresia.
AB  - Genetic mutations in alpha6beta4 integrin cause junctional epidermolysis bullosa
      with pyloric atresia, a genodermatosis characterized by blistering of the skin
      and pyloric occlusion. The lethal form of junctional epidermolysis bullosa with
      pyloric atresia has been mainly associated with the presence of premature
      termination codons in the mRNA encoding either the alpha6 or beta4 subunit
      causing rapid decay of the mutated transcript and absence of alpha6beta4
      integrin. In this study, we disclose the genetic background of lethal junctional
      epidermolysis bullosa with pyloric atresia in a patient presenting absent
      expression of alpha6 integrin despite normal steady-state level of the
      alpha6beta4 mRNA. Screening for mutation in the alpha6 gene detected a homozygous
      base pair substitution (286 C-to-T), which results in the substitution of a
      serine with a leucine residue (S47L). The amino acid substitution S47L localizes
      in the first beta-strand of the seven-bladed beta-propeller structure of the
      extracellular head of alpha6 integrin, and triggers a rapid proteolysis of the
      aberrant polypeptides involving the lysosomal degradation pathway. This study
      provides new insight into the pathogenic effect of a mis-sense mutation affecting
      a functional domain of a protein, and identifies a critical peptide sequence of
      the beta-propeller domain conserved among the alpha integrin cell receptors.

PMID- 14675180
TI  - Identification of a lethal form of epidermolysis bullosa simplex associated with
      a homozygous genetic mutation in plectin.
AB  - Genetic mutations in plectin, a cytoskeleton linker protein expressed in a large
      variety of tissues including skin, muscle, and nerves, cause epidermolysis
      bullosa simplex with muscular dystrophy, a recessive inherited disease
      characterized by blistering of the skin and late onset of muscular dystrophy, and
      Ogna epidermolysis bullosa simplex, a rare dominant inherited form of
      epidermolysis bullosa simplex with no muscular involvement. Here we report a
      novel homozygous genetic mutation (2727del14) in the plectin gene (PLEC1)
      associated with a lethal form of recessive inherited epidermolysis bullosa in a
      consanguineous family with three affected offspring. This new clinical variant of
      epidermolysis bullosa is characterized by general skin blistering, aplasia cutis
      of the limbs, developmental complications, and rapid demise after birth. Mutation
      2727del14 is the first genetic defect described in PLEC1 that disrupts the plakin
      domain of plectin. The severe phenotype of the patients may be linked to the role
      of the N-terminal domain in the function of plectin and develops the
      understanding of the genotype-phenotype correlations in the genodermatoses
      affecting the dermal-epidermal junction.

PMID- 14675181
TI  - Impaired trafficking of the desmoplakins in cultured Darier's disease
      keratinocytes.
AB  - Darier's disease is an autosomal dominantly inherited skin disorder characterized
      by loss of adhesion between epidermal cells, breakdown of desmosome-keratin
      filaments, and abnormal keratinization. ATP2A2 has been identified as the
      causative gene of Darier's disease. This gene encodes the sarco(endo)plasmic
      reticulum Ca2+-ATPase (SERCA) isoform 2 pump, which transports Ca2+ from the
      cytosol into the endoplasmic reticulum lumen to maintain a low cytosolic Ca2+
      concentration. Using indirect immunofluorescence and biochemical analysis, we
      investigated the distribution of key desmosomal proteins in normal human and
      Darier's disease keratinocytes under various calcium conditions. We show that
      inhibition of SERCA by thapsigargin in normal human keratinocytes impairs the
      trafficking of the desmoplakins, desmoglein, and desmocollin to the cell surface;
      these proteins show a diffuse cytoplasmic distribution and, together with
      plakoglobin, form detergent-insoluble aggregates. In Darier's disease
      keratinocytes, only the trafficking of desmoplakin is significantly inhibited; in
      these cells, desmoplakin forms insoluble aggregates when extracted with mild
      detergent. In contrast, the transmembrane proteins desmoglein and desmocollin are
      efficiently transported to the cell surface. These proteins, along with
      plakoglobin, remain equally distributed between detergent-soluble and -insoluble
      fractions. We also demonstrate an interaction between SERCA2 and desmoplakin
      during differentiation. Our results provide further insights into the critical
      role of calcium ATPases in maintaining epidermal integrity.

PMID- 14675182
TI  - A novel loss-of-function mutation (N48K) in the PTEN gene in a Spanish patient
      with Cowden disease.
AB  - Cowden disease, also known as multiple hamartoma syndrome, is a rare disease
      inherited in an autosomal dominant pattern, which confers a high risk of
      developing breast and thyroid carcinomas. Mutations in PTEN, a tumor suppressor
      gene located on chromosome 10q23, have been identified in patients with Cowden
      disease. In this work, the direct sequencing of all coding regions of the PTEN
      gene led us to the identification of N48K, a new germline PTEN missense mutation,
      in a patient suffering from Cowden disease. The genetic analysis of 200
      chromosomes from healthy individuals revealed that the variant was not common in
      our population. Moreover, by functional analysis we found that the ability of
      PTEN N48K mutant protein to inhibit the activation of the proto-oncogene PKB/Akt
      was impaired, supporting the involvement of N48K mutation in Cowden disease. Loss
      of heterozygosity using three microsatellites (D10S215, D10S541, and D10S564) and
      the complete sequence analysis of PTEN exons in breast and endometrial tumor
      samples from the same patient were also carried out in an attempt to identify
      additional PTEN somatic mutations. The lack of loss of heterozygosity or
      additional mutations in tumor samples suggests that abnormalities of the
      regulatory regions of the PTEN gene or haplo-insufficiency might occur in tumors
      from Cowden disease patients.

PMID- 14675183
TI  - HCR, a candidate gene for psoriasis, is expressed differently in psoriasis and
      other hyperproliferative skin disorders and is downregulated by interferon-gamma
      in keratinocytes.
AB  - We have previously shown that HCR is a good candidate gene for psoriasis based on
      its location in the PSORS1 locus, predicted secondary structure change of the
      associated allele, and expression pattern. To understand better the function of
      HCR, we studied how HCR expression is altered in hyperproliferative skin diseases
      other than psoriasis and in cancers. We examined also its regulation by different
      cytokines, growth factors, and antipsoriatic agents using quantitative RT-PCR
      (TaqMan) analysis and its location by immunostaining of keratinocyte cultures.
      Compared to psoriasis, HCR protein had a different distribution in chronic
      dermatitis, pityriasis rubra pilaris, mycosis fungoides, and chronic skin ulcers.
      In three of six grade III squamous cell carcinomas of the skin, four of four
      adenocarcinomas of the lung, and two of two ductal breast adenocarcinomas,
      positive cytoplasmic staining in cancer cells was detected. As in psoriasis, Ki67
      did not colocalize with HCR. In cell cultures, HCR staining was detected
      perinuclearly in the cytoplasm and in the nuclei, suggesting that the protein may
      have a role in both compartments. A 2-fold downregulation of HCR mRNA expression
      was observed on stimulation with interferon-gamma. Based on the observations that
      HCR is detected in cancers of epithelial origin in Ki67-negative areas and that
      interferon-gamma downregulates its expression, we suggest it to have an
      antiproliferative function.

PMID- 14675184
TI  - T cell receptor gene usage in desmoglein-3-specific T lymphocytes from patients
      with pemphigus vulgaris.
AB  - Pemphigus vulgaris (PV) is an autoimmune disease mediated by autoantibodies
      against desmoglein-3 (Dsg3). It has been documented that both humoral and
      cellular autoimmunity play essential roles in the development of PV. Recently, we
      identified that T cells from PV patients respond to three antigenic fragments on
      the ectodomain of Dsg3. These T cells are CD4 alpha/beta cells secreting a Th2
      like cytokine profile, and responding of Dsg3 in a restriction to HLA-DRBI*0402
      or 1401 alleles. Other characteristics of these cells, such as detailed
      epitope(s) and T cell receptors (TCRs) usage, however, have not been
      investigated. The purpose of this study is to determine detailed T cell
      epitope(s) and TCR genes utilized by Dsg3-specific T cells. Here, we found that
      Dsg3(AA145-192)-specific cells preferentially utilize the TCRVbeta13 gene, while
      Dsg3(AA240-303)- and Dsg3 (AA570-614)-specific cells utilize Vbeta7 and Vbeta17
      genes, respectively. Analysis of TCRValpha gene expression, it appears that
      Valpha22 gene is expressed by Dsg3(AA145-192)-specific cells, whereas the
      Valpha10 gene is predominantly utilized by Dsg3(AA240-303)-specific T cells.
      There are no specific utilization of Valpha gene in the group of cells
      proliferate to Dsg3 (AA570-614). We believe that this information will further
      our understanding of the properties of autoimmune T cells in patients with PV.

PMID- 14675185
TI  - Pathogenicity and epitope characteristics of anti-desmoglein-1 from pemphigus
      foliaceus patients expressing only IgG1 autoantibodies.
AB  - Pemphigus foliaceus (PF) is an antibody-mediated autoimmune disorder with IgG1
      and IgG4 as the predominant subclasses of autoantibodies against a desmosomal
      glycoprotein, desmoglein-1 (Dsg1). Previously, we found that the IgG4 anti-Dsg1
      autoantibodies only recognize a conformational epitope(s), whereas the IgG1
      autoantibodies recognize both conformational and linear epitopes but do not
      display pathogenicity in the passive transfer animal model. The purpose of this
      study was to analyze the epitopes recognized by autoanti-bodies from a subset of
      PF patients who only express anti-Dsg1 of the IgG1 isotype throughout the course
      of their diseases and to further characterize the pathogenicity of their IgG1
      anti-Dsg1. We found that IgG1 auto-antibodies in this subset of PF patients,
      similar to IgG4 autoantibodies from other PF patients, are able to bind both
      human and mouse skin and induce the experimental PF in mice. Moreover, a detailed
      epitope mapping reveals that the conformational epitopes recognized by IgG1
      autoantibodies from these PF patients are restricted to the first 161 amino acids
      of Dsg1, whereas the linear epitopes are spread throughout the entire ectodomain.
      In conclusion, our study reveals that the isotype of IgG does not necessarily
      determine the epitopes and pathogenicity of pemphigus autoantibodies.

PMID- 14675186
TI  - Interleukin-21 inhibits dendritic cell-mediated T cell activation and induction
      of contact hypersensitivity in vivo.
AB  - Interleukin (IL)-21 is a newly described cytokine that is produced by activated T
      cells and displays structural homology to IL-4 and IL-15. We here analyzed the
      role of IL-21 in dendritic cell (DC)-induced, T cell-mediated contact
      hypersensitivity (CHS) in vivo and on T cell activation and unspecific mixed
      lymphocyte reaction in vitro. By PCR, we demonstrate here constitutive expression
      of the specific IL-21 receptor and the common gamma-chain in DC, which together
      are able to mediate IL-21 signaling. Short-time incubation of in vitro generated
      DC with IL-21 significantly reduced their potential to induce an antigen-specific
      CD8+ T cell proliferation. Interestingly, 2h incubation of these DC with IL-21
      before injection completely inhibited the potential of these DC to induce a CHS
      reaction to the hapten fluorescein 5-isothiocyanate in vivo. Mice injected with
      IL-21-treated DC even failed to mount a CHS response after repetitive injection
      of non-IL-21-treated DC 2 weeks later, suggesting that an antigen-specific
      unresponsiveness can be induced by IL-21-treated DC. Our data demonstrate that IL
      21 is a new modulator of DC-T cell interaction with the potential to induce DC
      mediated antigen-specific tolerance.

PMID- 14675187
TI  - Dimethylfumarate is a potent inducer of apoptosis in human T cells.
AB  - Fumaric acid esters (FAE) have been used for the systemic treatment of psoriasis
      in Germany for almost 50 years. Recently, it has been shown that dimethylfumarate
      (DMF) as the main ingredient of the marketed FAE mixture is a potent inhibitor of
      the nuclear transcription factor NF-kappaB. DMF was also shown to induce
      apoptosis in various cells. Because T cells play a crucial role in psoriasis
      pathogenesis, we asked whether DMF and its main metabolite methylhydrogenfumarate
      (MHF) were able to induce apoptosis in these cells. Purified human T cells were
      treated with DMF and MHF (1-20 microg/mL) and stimulated with interleukin 2, anti
      CD3 antibodies or both for 48 h, and apoptosis was subsequently determined by the
      expression of Apo2.7 as well as by terminal deoxynucleotide transferase nick end
      labeling. The expression of antiapoptotic protein Bcl-2 was simultaneously
      determined. The results showed a dose-and-time dependent up-regulation of Apo2.7
      expression and DNA fragmentation by DMF preferable in stimulated T cells. MHF and
      the solvent dimethyl sulfoxide were without effect. DMF, but not MHF, led to a
      concentration-dependent decrease of Bcl-2 expression in interleukin-2-stimulated
      T cells. The data provide evidence that the effect of FAE treatment of psoriasis
      may at least in part be due to induction of apoptosis in activated T cells.

PMID- 14675188
TI  - Toll-like receptor expression in human keratinocytes: nuclear factor kappaB
      controlled gene activation by Staphylococcus aureus is toll-like receptor 2 but
      not toll-like receptor 4 or platelet activating factor receptor dependent.
AB  - Cultured primary human keratinocytes were screened for their expression of
      various members of the toll-like receptor (TLR) family. Keratinocytes were found
      to constitutively express TLR1, TLR2, TLR3, TLR5, and TLR9 but not TLR4, TLR6,
      TLR7, TLR8, or TLR10 as shown by polymerase chain reaction analysis. The
      expression of the crucial receptor for signaling of staphylococcal compounds TLR2
      was also confirmed by immunohistochemistry, in contrast to TLR4, which showed a
      negative staining pattern. Next, we analyzed the activation of the
      proinflammatory nuclear transcription factor kappaB by Staphylococcus aureus
      strain 8325-4. Using nuclear extract gel shifts, RelA staining, and luciferase
      reporter transfection plasmids we found a clear induction of nuclear factor
      kappaB translocation by the bacteria. This translocation induced the
      transcription of nuclear factor kappaB controlled genes such as inducible nitric
      oxide synthetase, COX2, and interleukin-8. Transcription of these genes was
      followed by production of increased amounts of interleukin-8 protein and NO.
      Inhibition experiments using monoclonal antibodies and the specific platelet
      activating factor receptor inhibitor CV3988 showed that nuclear factor kappaB
      activation by S. aureus was TLR2 but not TLR4 or platelet activating factor
      receptor dependent. In line, the purified staphylococcal cell wall components
      lipoteichoic acid and peptidoglycan, known to signal through TLR2, also showed
      nuclear factor kappaB translocation in human keratinocytes, indicating a crucial
      role of the staphylococcal cell wall in the innate immune stimulation of human
      keratinocytes. These results help to explain the complex activation of human
      keratinocytes by S. aureus and its cell wall components in various inflammatory
      disorders of the skin.

PMID- 14675190
TI  - The autoantigen of anti-p200 pemphigoid is an acidic noncollagenous N-linked
      glycoprotein of the cutaneous basement membrane.
AB  - Anti-p200 pemphigoid is an autoimmune subepidermal blistering disease
      characterized by autoantibodies to a 200-kDa protein (p200) of the dermal
      epidermal junction (DEJ). p200 has been demonstrated to be distinct from all
      major DEJ autoantigens and is thought to be important for cell-matrix adhesion.
      This study provides the first biochemical characterization of p200. Differential
      extraction experiments demonstrated that efficient recovery of p200 from the
      dermis was strongly dependent on the presence of reducing agents, suggesting that
      it forms highly insoluble oligomers and/or is extensively cross-linked to other
      extracellular matrix components by disulfide bonding. p200 was resistant to
      digestion with bacterial collagenase, whereas this treatment did degrade major
      collagenous proteins of the dermis, including type I, VI, and VII collagen. This
      finding firmly established the noncollagenous nature of p200. N-Glycosidase F
      reduced the molecular size of the p200 autoantigen from 200 to 190 kDa without
      decreasing its immunoreactivity. In contrast, digestion of p200 with
      neuraminidase, O-glycosidase, chondroitinase ABC, and heparitinase I had no
      effect on its electrophoretic mobility. These data suggest that the p200 molecule
      contains N-glycans but lacks O-linked oligosaccharides and chondroitin/heparan
      sulfate side chains. Two-dimensional gel electrophoresis demonstrated that p200
      is an acidic protein with an isoelectric point of 5.4 to 5.6. Six different p200
      specific sera recognized an identical protein spot of two-dimensionally separated
      dermal extracts, confirming that patients with this novel autoimmune disease
      indeed form a single pathobiochemical entity.

PMID- 14675189
TI  - Interleukin-3 in cooperation with transforming growth factor beta induces
      granulocyte macrophage colony stimulating factor independent differentiation of
      human CD34+ hematopoietic progenitor cells into dendritic cells with features of
      Langerhans cells.
AB  - Recently, we have reported that M-CSF in cooperation with TGF-beta1 can induce
      Langerhans cell (LC) development from hematopoietic progenitor cells (HPCs)
      without GM-CSF. In the present study, we examined whether TGF-beta1 changes the
      differentiation of HPCs induced by IL-3 towards LC development. We cultured HPCs
      in a serum-free medium in the presence of IL-3 and a combination cytokines
      including Flt3L, SCF, and TNF-alpha with or without TGF-beta1. DCs induced by the
      IL-3 culture (IL-3 DCs) did not significantly differ from those induced by the GM
      CSF culture (GM-CSF DCs). Namely, both expressed CDla, F-cadherin, and Langerin
      in the presence of TGF-beta1 and stimulated allogeneic T cells at a similar
      magnitude. In contrast to GM-CSF DCs, IL-3 DCs lacked the expression of Birbeck
      granules (BGs) in spite of their expression of Langerin. When we compared the
      expression of Langerin between these two DCs, however, it became clear that both
      Langerin protein and mRNA were significantly lower in IL-3 DCs than in GM-CSF
      DCs. These studies again demonstrated the ability of TGF-beta1 to polarize the
      differentiation of HPCs induced by IL-3 towards LC development, although IL-3 DCs
      were unable to form BGs partly because of their poor ability to induce Langerin.

PMID- 14675191
TI  - Immunopathologic features of allergic contact dermatitis in humans: participation
      of plasmacytoid dendritic cells in the pathogenesis of the disease?
AB  - Contrary to our abundant knowledge about the sensitization phase of human contact
      hypersensitivity, little is known about the cell types orchestrating the effector
      phase. In order to address this issue, we phenotypically analyzed biopsies from
      72 h epicutaneous patch test reactions (n=10) and normal human skin (n=5) for the
      presence of various leukocyte differentiation antigens. The inflammatory
      infiltrate was dominated by CD3+/CD4+ T cells with approximately 30% of the cells
      coexpressing CD25 and CTLA-4, a phenotype consistent with either activated
      effector or regulatory T cells. In our search for professional antigen-presenting
      cells, we were surprised to find not only sizeable numbers of CD1a+ dendritic
      cells and CD1c+ dendritic cells, but also of CD123+, CD45RA+, BDCA-2+, CLA+, and
      CD62L+ plasmacytoid dendritic cells. Although virtually absent in normal human
      skin, these cells were detectable already 6 h after hapten challenge and were
      often found in close proximity to CD56+ natural killer cells, indicative of a
      functional interaction between these cell types. The detailed knowledge of the
      cellular composition of the inflammatory infiltrate in allergic contact
      dermatitis and its kinetics should form the basis for the investigation of the
      immunologic and molecular events operative in the perpetuation and resolution of
      the eczematous response.

PMID- 14675192
TI  - Mechanisms for a novel immune evasion strategy in the scabies mite sarcoptes
      scabiei: a multigene family of inactivated serine proteases.
AB  - Parasitic infestation of the skin by the mite Sarcoptes scabiei is a significant
      problem worldwide, particularly in socially disadvantaged communities. A
      multigene family of at least 24 homologs of a serine protease allergen have been
      identified in S. scabiei. Surprisingly, the products of all but one of these
      genes are predicted to be catalytically inactive, due to mutations at a critical
      triad of amino acids at the active site. We discuss the possibility that these
      genes for inactivated proteases have been conserved because they mediate a novel
      host defense evasion strategy that the mite has evolved as an adaptation to
      parasitism of the epidermis. The identification of this family, and elucidation
      of its value to the parasite, may present an unanticipated approach to protective
      vaccination.

PMID- 14675193
TI  - Generation of a large number of connective tissue type mast cells by culture of
      murine fetal skin cells.
AB  - We describe a novel culture system for generating large numbers of murine skin
      associated mast cells and distinguish their characteristics from bone marrow
      derived cultured mast cells. Culture of day 16 fetal skin single cell suspensions
      in the presence of interleukin-3 and stem cell factor allowed expansion and
      maturation of mast cells in the presence of stromal cells. The average yield of
      mast cells after 2 wk was 7.3 million cells per fetus at a purity of 96%. These
      fetal skin-derived cultured mast cells increased their histamine content in a
      time-dependent manner to 3.6 pg per cell after 2 wk and 6.7 pg per cell after 4
      wk. Phenotypic analyses revealed much greater expression of CD49b and CD81 and
      lesser expression of CD77 and CD102 on fetal skin-derived cultured mast cells as
      compared with bone marrow-derived cultured mast cells. These findings suggest a
      close similarity between fetal skin-derived cultured mast cells and freshly
      isolated cutaneous mast cells. Connective tissue mast cell characteristics of
      fetal skin-derived cultured mast cells were evidenced by: (1) their greater
      histamine content than bone marrow-derived cultured mast cells; (2) the presence
      of heparin; and (3) their degranulation in response to compound 48/80 and
      substance P. Importantly, fetal skin-derived cultured mast cells secreted greater
      amounts of interleukin-13 but much less MIP-1beta and interleukin-6 than bone
      marrow-derived cultured mast cells in response to ionomycin. Thus fetal skin
      derived cultured mast cells have many characteristics distinct from bone marrow
      derived cultured mast cells and can be used as a model of cutaneous mast cells to
      discern their functions.

PMID- 14675194
TI  - Tumor necrosis factor related apoptosis inducing ligand triggers apoptosis in
      dividing but not in differentiating human epidermal keratinocytes.
AB  - Using serial analysis of gene expression we have previously identified the
      expression of several pro-apoptotic and anti-apoptotic genes in cultured human
      primary epidermal keratinocytes, including tumor necrosis factor related
      apoptosis inducing ligand (TRAIL). TRAIL is a potent inducer of apoptosis in
      transformed and tumor cell lines, but usually not in other cells. Here we present
      a study on the effect of TRAIL on cultured keratinocytes. It is shown that
      differentiated and undifferentiated keratinocytes undergo apoptosis after
      addition of TRAIL to the medium as determined by morphologic and biochemical
      criteria, such as cellular shrinkage and activation of caspases. The sensitivity
      for TRAIL differs greatly between undifferentiated and differentiating
      keratinocytes, however, with undifferentiated cells being much more susceptible
      to apoptosis. Commitment to terminal differentiation in the absence of TRAIL does
      not in itself induce apoptosis. In contrast to the promyelocytic cell line HL60,
      internucleosomal DNA fragmentation is not observed in keratinocytes, as assessed
      by flow cytometric analysis and agarose gel electrophoresis. Interestingly, the
      prime effector of DNA fragmentation, DNA fragmentation factor of 40 kDa (DFF40),
      is expressed in keratinocytes, yet internucleosomal cleavage fails to occur. Our
      data indicate that programmed cell death during keratinocyte differentiation is
      distinct from receptor-mediated apoptosis in response to a death ligand.

PMID- 14675195
TI  - The organization of human epidermis: functional epidermal units and phi
      proportionality.
AB  - The concept that mammalian epidermis is structurally organized into functional
      epidermal units has been proposed on the basis of stratum corneum (SC)
      architecture, proliferation kinetics, melanocyte:keratinocyte ratios (1:36), and,
      more recently, Langerhans cell: epidermal cell ratios (1:53). This article
      examines the concept of functional epidermal units in human skin in which the
      maintenance of phi (1.618034) proportionality provides a central organizing
      principle. The following empirical measurements were used: 75,346 nucleated
      epidermal cells per mm2, 1394 Langerhans cells per mm2, 1999 melanocytes per mm2,
      16 (SC) layers, 900-microm2 corneocyte surface area, 17,778 corneocytes per mm2,
      14-d (SC) turnover time, and 93,124 per mm2 total epidermal cells. Given these
      empirical data: (1) the number of corneocytes is a mean proportional between the
      sum of the Langerhans cell + melanocyte populations and the number of epidermal
      cells, 3393/17,778-17,778/93,124; (2) the ratio of nucleated epidermal cells over
      corneocytes is phi proportional, 75,346/17,778 approximately phi3; (3) assuming
      similar 14-d turnover times for the (SC) and Malpighian epidermis, the number of
      corneocytes results from subtraction of a cellular fraction equal to
      approximately 2/phi2 x the number of living cells, 75,436 - (2/phi2 x 75,346)
      approximately 17,778; and (4) if total epidermal turnover time equals (SC)
      turnover time x the ratio of living/dead cells, then compartmental turnover times
      are unequal (14 d for (SC) to 45.3 d for nucleated epidermis approximately
      1/2phi) and cellular replacement rates are 52.9 corneocytes/69.3 keratinocytes
      per mm2 per h approximately 2/phi2. These empirically derived equivalences
      provide logicomathematical support for the presence of functional epidermal units
      in human skin. Validation of a phi proportional unit architecture in human
      epidermis will be important for tissue engineering of skin and the design of
      instruments for skin measurement.

PMID- 14675196
TI  - Modulation of gene expression induced in human epidermis by environmental stress
      in vivo.
AB  - Environmental insults on the skin induce biologic responses through the
      modulation of expression of genes implicated in different cell functions. The aim
      of this study was to investigate the modulation of gene expression profile in
      human epidermis in vivo following different stresses. We determined the
      modulations of gene expression using cDNA macroarray in the epidermis of 28
      healthy volunteers, following mild and physiologic insults, including: (1), tape
      stripping; (2) application of 10% sodium dodecyl sulfate; (3) daily application
      of vaseline; and (4), exposure to one minimal erythema dose of solar-simulated
      radiation. The analysis was performed 19 h after treatment. The reverse
      transcription-polymerase chain reaction method was used to confirm our results.
      We showed that: (1) the intensity of gene modulation was variable among the
      volunteers following the same skin stress; (2) the nature and intensity of skin
      treatment modified the pattern of gene expression; and (3) some genes were
      modulated only by specific stress, some others are modulated irrespective of the
      stress. GADD45, Bax, SAS, and granulocyte chemotactic protein-2 were
      overexpressed exclusively following solar-simulated radiation, whereas tape
      stripping led to the modulation of genes implicated in different pathways
      (inflammation, cell proliferation, cell differentiation, detoxification, etc.).
      Concerning common gene modulation, MRP8 and MRP14 were highly upregulated in
      human skin epidermis after solar-simulated radiation, vaseline application or
      tape stripping, and to a lower extent after sodium dodecyl sulfate. Such
      upregulation of the MRP 8/14 genes was confirmed at the protein level in an ex
      vivo skin culture model following tape stripping and solar-simulated radiation.
      Together, these results suggest that MRP8 and MRP14 may be general, yet highly
      sensitive, markers for a great variety of skin stresses and that they are
      implicated in several epidermal repair pathways.

PMID- 14675197
TI  - Transcriptional profiling of epidermal keratinocytes: comparison of genes
      expressed in skin, cultured keratinocytes, and reconstituted epidermis, using
      large DNA microarrays.
AB  - Epidermal keratinocytes are complex cells that create a unique three-dimensional
      (3-D) structure, differentiate through a multistage process, and respond to
      extracellular stimuli from nearby cells. Consequently, keratinocytes express many
      genes, i.e., have a relatively large "transcriptome." To determine which of the
      expressed genes are innate to keratinocytes, which are specific for the
      differentiation and 3-D architecture, and which are induced by other cell types,
      we compared the transcriptomes of skin from human subjects, differentiating 3-D
      reconstituted epidermis, cultured keratinocytes, and nonkeratinocyte cell types.
      Using large oligonucleotide microarrays, we analyzed five or more replicates of
      each, which yielded statistically consistent data and allowed identification of
      the differentially expressed genes. Epidermal keratinocytes, unlike other cells,
      express many proteases and protease inhibitors and genes that protect from UV
      light. Skin specifically expresses a higher number of receptors, secreted
      proteins, and transcription factors, perhaps influenced by the presence of
      nonkeratinocyte cell types. Surprisingly, mitochondrial proteins were
      significantly suppressed in skin, suggesting a low metabolic rate. Three
      dimensional samples, skin and reconstituted epidermis, are similar to each other,
      expressing epidermal differentiation markers. Cultured keratinocytes express many
      cell-cycle and DNA replication genes, as well as integrins and extracellular
      matrix proteins. These results define innate, architecture-specific, and cell
      type-regulated genes in epidermis.

PMID- 14675198
TI  - Transcriptional control of the mouse Col7a1 gene in keratinocytes: basal and
      transforming growth factor-beta regulated expression.
AB  - Anchoring fibrils at the cutaneous basement membrane zone of the stratified
      squamous epithelia are essential to maintaining skin integrity, as absence of
      these structures leads to the chronic blistering disease, dystrophic
      epidermolysis bullosa. Type VII collagen, the major component of anchoring
      fibrils, is synthesized primarily by basal keratinocytes and to a lesser degree
      by dermal fibroblasts. To elucidate the transcriptional control elements of the
      type VII collagen gene (Col7a1), 3 kb of 5' flanking sequence of the mouse gene
      was cloned, sequenced, and fused to the chloramphenicol acetyltransferase
      reporter gene. Promoter deletion analyses revealed that 560 bp of Col7a1 5'
      flanking sequence was sufficient and necessary for basal level of transcription
      in cultured murine keratinocytes. Mutagenesis of DNA sequences with similarity to
      consensus binding sites for transcription factors, including Sp1/Sp3, AP2, AP1,
      and Smads, within the p-560Col7a1 promoter/chloramphenicol acetyltransferase
      construct, coupled with DNA binding assays, revealed the importance of these
      sites for basal Col7a1 expression. The effect of transforming growth factor beta,
      an activator of Col7a1 expression in keratinocytes and dermal fibroblasts, was
      examined using the same Col7a1 promoter/chloramphenicol acetyltransferase
      constructs. These analyses demonstrated that transforming growth factor beta1
      stimulation of Col7a1 transcription is dependent on a putative interaction
      between Smads and AP1. Interestingly, the Smad-like binding site was essential
      for both basal and transforming growth factor beta1 stimulated Col7a1
      transcription. Collectively, these findings attest to the complex regulation of
      Col7a1 transcription in epidermal keratinocytes.

PMID- 14675199
TI  - Crucial effects of fibroblasts and keratinocyte growth factor on morphogenesis of
      reconstituted human oral epithelium.
AB  - The connective tissue is known to have a general supportive effect for the
      development of the overlying epithelium; however, the more specific effects of
      fibroblasts and the involvement of their product, keratinocyte growth factor, on
      oral epithelial morphogenesis have not yet been addressed. Therefore, the purpose
      of this study was to investigate the effects of fibroblasts and keratinocyte
      growth factor on human oral epithelial morphogenesis in vitro. Reconstituted
      human oral epithelium was generated from primary human oral keratinocytes and
      fibroblasts by use of an organotypic cell culture model in a defined medium.
      Addition of fibroblasts to the collagen biomatrix increased total epithelial
      thickness from 28.0+/-5.0 microm to 66.1+/-8.6 microm (p=0.028), and basal cell
      proliferation from 3.6+/-0.7% to 16.6+/-1.1% (p=0.025). Presence of fibroblasts
      profoundly influenced the pattern of epithelial differentiation, and induced a
      switch in the pattern of cell death, from a predominance of spontaneous cell
      death in the basal cell layer (from 4.7+/-0.6% to 1.8+/-0.3%, p=0.029) to a more
      prevalent cell death due to terminal differentiation in the suprabasal cell layer
      (from 4.0+/- 0.1% to 5.4+/-0.1%, p=0.034). Keratinocyte growth factor promoted
      epithelial growth, but did not significantly enhance epithelial differentiation,
      demonstrating that fibroblasts possess additional mechanisms to keratinocyte
      growth factor synthesis that can modulate differentiation of reconstituted human
      oral epithelium.

PMID- 14675200
TI  - Aquaporin 3 colocates with phospholipase d2 in caveolin-rich membrane
      microdomains and is downregulated upon keratinocyte differentiation.
AB  - Aquaporin 3 is a channel that transports both water and glycerol. Aquaporin 3
      deficient mice exhibit skin defects, including decreased glycerol content and
      impairment of water holding capacity, barrier recovery, and wound healing.
      Whether aquaporin 3 and its glycerol transporting capacity are involved in
      regulating keratinocyte function, we have previously shown that phospholipase D2
      can metabolize phospholipids in the presence of glycerol to yield
      phosphatidylglycerol. We hypothesized that aquaporin 3 is involved in the
      regulation of keratinocyte function by a mechanism involving the interaction
      between aquaporin 3 and phospholipase D. Using sucrose gradient centrifugation,
      immunoprecipitation analysis, and confocal microscopy, we found that aquaporin 3
      and phospholipase D2 colocalized in caveolin-rich membrane microdomains. In
      addition, aquaporin 3 expression was downregulated at the transcriptional level
      and glycerol uptake was reduced upon primary mouse keratinocytes to
      differentiation in response to an elevated extracellular calcium concentration or
      1,25-dihydroxyvitamin D3. Our results suggest that aquaporin 3 and phospholipase
      D2 form a signaling module in lipid rafts, where aquaporin 3 transports glycerol
      to phospholipase D2 for the synthesis of phosphatidylglycerol.
      Phosphatidylglycerol, as a bioactive lipid, could potentially mediate the effects
      of the aquaporin 3-phospholipase D2 signaling module, with aquaporin 3 as a
      modulatory unit, in the regulation of keratinocyte function.

PMID- 14675201
TI  - Corticotropin-releasing hormone inhibits nuclear factor-kappaB pathway in human
      HaCaT keratinocytes.
AB  - Treatment of human HaCaT keratinocytes with corticotropin-releasing hormone
      modulates cell proliferation and expression of inflammation markers. In this
      study we report that corticotropin-releasing hormone also inhibits nuclear factor
      kappaB binding and transcriptional activity. Incubating cells in the absence of
      growth factors increased nuclear factor-kappaB activity; this effect was
      significantly attenuated by corticotropin-releasing hormone. Specifically,
      corticotropin-releasing hormone downregulated p50/p50 and p50/p65 dimers of
      nuclear factor-kappaB, diminished kappaB-driven CAT reporter gene activity and
      inhibited IkappaB-beta degradation. Moreover, corticotropin-releasing hormone
      inhibited the trans-cription of the nuclear factor-kappaB responsive genes,
      interleukin-2 and heat shock protein 90.

PMID- 14675202
TI  - 17beta-estradiol inhibits oxidative stress-induced apoptosis in keratinocytes by
      promoting Bcl-2 expression.
AB  - We examined in vitro effects of 17beta-estradiol on H2O2-induced apoptosis in
      human keratinocytes. 17beta-estradiol prevented the H2O2-induced apoptosis. H2O2
      decreased, whereas 17beta-estradiol increased Bcl-2 protein and mRNA levels in
      keratinocytes, and H2O2 plus 17beta-estradiol led to basal levels. Overexpression
      of Bcl-2 protected keratinocytes against H2O2-induced apoptosis, indicating the
      anti-apoptotic effect of Bcl-2. H2O2 suppressed, whereas 17beta-estradiol
      enhanced bcl-2 promoter activity, and H2O2 plus 17beta-estradiol led to basal
      activity. Cyclic adenosine monophosphate (cAMP) response element on bcl-2
      promoter was responsible for the effects of 17beta-estradiol and H2O2. Bcl-2
      expression was enhanced by membrane-impermeable bovine serum albumin-conjugated
      17beta-estradiol, indicating the effects via membrane 17beta-estradiol-binding
      sites. H2O2 decreased, whereas 17beta-estradiol increased the amount of
      phosphorylated cAMP response element-binding protein and cAMP response element
      dependent transcriptional activity, and H2O2 plus 17beta-estradiol led to basal
      levels. H-89, an inhibitor of cAMP-dependent protein kinase A, suppressed basal
      and 17beta-estradiol-induced cAMP response element-binding protein
      phosphorylation, cAMP response element-dependent transcriptional activity, Bcl-2
      expression, and apoptosis resistance. The cAMP analog, dibutyryl cAMP, enhanced
      cAMP response element-binding protein phosphorylation, cAMP response element
      dependent transcriptional activity, Bcl-2 expression, and apoptosis resistance.
      17Beta-estradiol increased intracellular cAMP level and protein kinase A
      activity, whereas these were not altered by H2O2. Keratinocytes expressed mRNA
      for estrogen receptor beta and guanine nucleotide-binding protein-coupled
      receptor, GPR30. GPR30 anti-sense oligonucleotide did, but anti-sense estrogen
      receptor beta did not suppress 17beta-estradiol-induced cAMP signal, cAMP
      response element-binding protein phosphorylation, Bcl-2 expression, and apoptosis
      resistance. These results suggest that 17beta-estradiol may enhance Bcl-2
      expression and prevent H2O2-induced apoptosis by phosphorylating cAMP response
      element-binding protein via cAMP/protein kinase A pathway in keratinocytes. These
      effects of 17beta-estradiol may be mediated via membrane GPR30.

PMID- 14675203
TI  - p53 codon 72 Arg homozygotes are associated with an increased risk of cutaneous
      melanoma.
AB  - The p53 gene plays an important role in cell cycle control, facilitating DNA
      repair activities in response to DNA damage. Aberrant cell cycle control impairs
      DNA repair and increases the probability of mutations that can lead to
      carcinogenesis. The p53 gene is polymorphic at codon 72 (Arg/Pro) of its protein,
      which is functionally distinct, leading to inquiry into its role in
      carcinogenesis. In this hospital-based case-control study of 289 newly diagnosed
      patients with melanoma and 308 cancer-free control subjects, we evaluated whether
      the p53 codon 72 variant is associated with risk of cutaneous melanoma (CM). The
      controls were frequency-matched to the cases by age, sex, and ethnicity. The
      frequency of the p53 Arg allele was 78.2% in cases and 73.2% in controls
      (p=0.045), and the genotype frequencies of p53 Arg/Arg, Arg/Pro, and Pro/Pro were
      62.6%, 31.1%, and 6.3%, respectively, in the cases, and 53.9%, 38.6%, and 7.5%,
      respectively, in the controls (p=0.096). Logistic regression analysis revealed
      that the p53 Arg/Arg genotype was associated with a significantly increased risk
      of melanoma (adjusted odds ratio (OR)=1.43; 95% confidence interval (CI)=1.02
      2.02) compared with other genotypes, and this association was more evident in
      subgroups of older subjects (OR=2.32; 95% CI=1.39-388), and subjects with
      Fitzpatrick's skin type III or IV (OR=1.69; 95% CI=1.11-2.59). In conclusion,
      this study found some evidence that in subjects over 50, p53 Arg/Arg genotype is
      associated with increased risk of CM as compared to genotypes Arg/Pro or Pro/Pro.
      Further larger studies are needed to substantiate our findings.

PMID- 14675204
TI  - Expression and function of neurotrophins and their receptors in cultured human
      keratinocytes.
AB  - Whereas nerve growth factor has been extensively studied in human keratinocytes,
      little is known on the role of other members of the neurotrophin family. We
      investigated the expression and function of neurotrophins and neurotrophin
      receptors in cultured human keratinocytes. We demonstrated by reverse
      transcription-polymerase chain reaction that keratinocytes synthesize
      neurotrophin-3, brain-derived neurotrophic factor, and neurotrophin-4/5. These
      cells also express tyrosinase kinase A and C, the nerve growth factor and neuro
      trophin-3 high-affinity receptors, respectively. On the other hand, only the
      truncated extracellular isoform of tyrosinase kinase B, the high-affinity brain
      derived neurotrophic factor and neurotrophin-4/5 receptor, is detected in
      keratinocytes. Moreover, neurotrophin-3, brain-derived neurotrophic factor, and
      neurotrophin-4/5 proteins are secreted by human keratinocytes at low levels.
      Keratinocyte stem cells synthesize the highest amounts of nerve growth factor,
      while they secrete higher levels of nerve growth factor as compared with transit
      amplifying cells. Neurotrophin-3 stimulates keratinocyte proliferation, where
      brain-derived neurotrophic factor or neurotrophin-4/5 does not exert any effect
      on keratinocyte proliferation. Addition of neurotrophin-3 slightly upregulates
      the secretion of nerve growth factor, whereas nerve growth factor strongly
      augments neurotrophin-3 release. Ultraviolet B irradiation downregulates nerve
      growth factor, whereas it augments neurotrophin-3 and neurotrophin-4/5 protein
      levels. Ultraviolet A irradiation increases the level of neurotrophin-3, whereas
      it does not exert any effect on the other neurotrophins. Finally, neurotrophins
      other than nerve growth factor fail to protect human keratinocytes from
      ultraviolet B-induced apoptosis. This work delineates a functional neurotrophin
      network, which may contribute to epidermal homeostasis.

PMID- 14675205
TI  - Contribution of flow cytometry in the diagnosis of cutaneous lymphoid lesions.
AB  - The histologic diagnosis of cutaneous lymphoid lesions remains one of the most
      challenging areas of dermatopathology and is augmented by incorporation of
      immunophenotypic and genotypic data. To improve the analysis of surface Ig light
      chain expression and to increase the yield of immunophenotypic data obtained from
      skin biopsies, we evaluated the utility of flow cytometry in cutaneous lymphoid
      infiltrates. Flow cytometric immunophenotypic analyses were performed on skin
      specimens of 19 patients as a part of diagnostic procedures. We found that skin
      biopsy specimens, including a routine punch biopsy, yield sufficient material for
      diagnostic flow cytometry. One reactive lymphoid hyperplasia showed polyclonal B
      cells and no aberrant T cell populations. Ig light chain restriction was detected
      by flow cytometry and contributed to the diagnosis in 88% (15 of 17) of cutaneous
      primary or secondary B cell lymphomas, compared to 37% (three of eight) by
      immunohistochemistry. Nearly one-third of these cases were histologically
      suspicious but difficult lesions due to processing artifact, mixed cellular
      infiltrate, or paucity of abnormal cells. Additional markers (3-23) were analyzed
      by flow cytometry on 15 specimens, and contributed to subclassification of the
      lymphomas. Our experience demonstrates that flow cytometry can be successfully
      applied to routine skin biopsies and contributes to the diagnosis and
      subclassification of cutaneous lymphoid lesions.

PMID- 14675206
TI  - Presence of human papillomavirus DNA in plucked eyebrow hairs is associated with
      a history of cutaneous squamous cell carcinoma.
AB  - A role for cutaneous human papillomaviruses (HPV) has been proposed in the
      development of skin cancer. Well-designed epidemiologic studies to demonstrate an
      association between HPV infection and skin cancer are extremely rare. To identify
      HPV infection as a potential risk factor, we investigated the association between
      the presence of HPV DNA in eyebrow hairs and a history of cutaneous squamous cell
      carcinoma. A case-control study was designed consisting of 155 immunocompetent
      individuals with a history of squamous cell carcinoma and 371 controls without
      skin cancer. DNA extracted from plucked eyebrow hairs collected from the study
      population was analyzed with a cutaneous HPV subgroup polymerase chain reaction
      and newly designed HPV type specific polymerase chain reactions for HPV 2, 5, 8,
      15, 16, 20, 24, and 38. HPV DNA was detected in 63.1% of the total study
      population. The presence of HPV DNA was associated with age (p=0.0002) and male
      sex (p=0.02), but not with sun exposure, skin type, and smoking. After adjustment
      for age and sex, the presence of HPV DNA in eyebrow hairs was associated with a
      history of squamous cell carcinoma (odds ratio 1.7, 95% confidence interval 1.1;
      2.7). HPV type specific analysis revealed that no HPV type stood out. The high
      risk mucosal type HPV 16 and the skin wart type HPV 2 were rarely found in this
      study (<0.2%). The positive association found between the presence of HPV DNA in
      eyebrow hairs and a history of squamous cell carcinoma warrants further research
      into the role that HPV infection plays in the development of cutaneous squamous
      cell carcinoma.

PMID- 14675208
TI  - Expression and activity of arginase isoenzymes during normal and diabetes
      impaired skin repair.
AB  - Within the past years, an important role for nitric oxide (NO) in skin repair has
      been well defined. As NO is synthesized from L-arginine by NO synthases (NOS),
      the availability of L-arginine might be one rate-limiting factor of NO production
      at the wound site. Upon injury, arginase-1 and -2 mRNA, protein, and activity
      were strongly induced reaching a maximum between day 3 and day 7 postwounding.
      Immunohistochemistry colocalized both arginases and the inducible NOS (iNOS) at
      epithelial sites at the margins of the wound. Notably, diabetes-impaired skin
      repair in leptin-deficient mice (diabetes/diabetes, db/db; and obese/obese,
      ob/ob) was characterized by an abnormally elevated arginase activity in wound
      tissue in the absence of an expression of iNOS. Expression analyses demonstrated
      that arginase-1 contributed to increased arginase activities in impaired repair.
      Interestingly, an improved healing of chronic wound situations in leptin
      supplemented ob/ob mice was strongly associated with an adjustment of the
      dysregulated expression of L-arginine-converting enzymes: an attenuated iNOS
      expression was upregulated early in repair and an augmented arginase-1 expression
      and activity was downregulated in the presence of markedly elevated numbers of
      macrophages during late repair. These data suggest a coordinated consumption of L
      arginine by the NOS and arginase enzymatic pathways at the wound site as a
      prerequisite for a balanced NO (via iNOS) and polyamine (via arginases) synthesis
      that drives a normal skin repair.

PMID- 14675207
TI  - An N-terminal 80 kDa recombinant fragment of human thrombospondin-2 inhibits
      vascular endothelial growth factor induced endothelial cell migration in vitro
      and tumor growth and angiogenesis in vivo.
AB  - We have previously shown that stable overexpression of the thrombospondin-2 (TSP
      2) gene inhibited the tumor growth and angiogenesis of human squamous cell
      carcinoma xenotransplants. To investigate the potential antitumoral efficacy of
      systemic TSP-2 therapy, we expressed a recombinant 80 kDa fragment of human TSP-2
      (TSP-2/NTF), encompassing the N-terminal globular region through the three type 1
      repeats, in human kidney 293 EBNA cells, using a modified pCEP4 expression
      vector. Daily intraperitoneal injections of TSP-2/NTF resulted in a significant
      inhibition of the growth of human A431 squamous cell carcinomas in vivo and in
      reduced tumor vascularization. To further investigate possible mechanisms of the
      antiangiogenic activity of TSP-2/NTF, several in vitro angiogenesis assays were
      performed in human dermal microvascular endothelial cells. TSP-2/NTF inhibited
      vascular endothelial growth factor induced migration of human dermal
      microvascular endothelial cells and inhibited tube formation on Matrigel in
      vitro. TSP-2/NTF also inhibited vascular endothelial growth factor induced
      angiogenesis in an in vivo Matrigel assay. Moreover, TSP-2/NTF potently induced
      human dermal microvascular endothelial cell apoptosis in vitro but did not affect
      A431 tumor cell proliferation or apoptosis. These findings identify TSP-2/NTF as
      a potent systemic inhibitor of tumor growth and angiogenesis, acting by direct
      inhibition of several endothelial cell functions involved in neovascularization.

PMID- 14675209
TI  - The importance of cationic amino acid transporter expression in human skin.

PMID- 14675210
TI  - The 97-kDa (LABD97) and 120-kDa (LAD-1) fragments of bullous pemphigoid antigen
      180/type XVII collagen have different N-termini.

PMID- 14675211
TI  - Altered distribution of calcium in facial epidermis of aged adults.

PMID- 14675212
TI  - Detection and mutation screening of Malassezia sympodialis sequences coding for
      the Mal s 1 allergen implicated in atopic dermatitis.

PMID- 14675213
TI  - Genetic basis of male pattern baldness.

PMID- 14675219
TI  - Cell movement in the hair follicle dermis - more than a two-way street?

PMID- 14675222
TI  - A mouthful of epithelial-mesenchymal interactions.

PMID- 14675223
TI  - P for probability and p for p53.

PMID- 14675224
TI  - Assessment of itch: more to be learned and improvements to be made.

PMID- 14675225
TI  - General psychiatric services for adults with intellectual disability and mental
      illness.
AB  - BACKGROUND: Adults with intellectual disability (ID) and mental illness may use
      general or specialist psychiatric services. This review aims to assess if there
      is evidence for a difference in outcome between them. METHODS: A literature
      review was conducted using a variety of electronic databases and hand-search
      strategies to identify all studies evaluating the outcome of people with ID and
      mental illness using general psychiatric services. RESULTS: There is no
      conclusive evidence to favour the use of general or specialist psychiatric
      services. People with ID stay less time on general psychiatric than specialist
      inpatient units. People with severe ID appear not to be well served in general
      services. Older studies of inpatient samples suggest a worse outcome for people
      with ID. Novel specialist services generally improve upon pre-existing general
      services. Assertive outreach in general services may preferentially benefit those
      with ID. Recent studies suggest similar lengths of stay in general psychiatric
      beds for people with and without ID. CONCLUSIONS: Although 27 studies were
      located, only two were randomized controlled trials. The evidence is poor quality
      therefore further evaluation of services employing a variety of designs need to
      be employed to give more robust evidence as to which services are preferred.

PMID- 14675226
TI  - Psychiatric inpatient care for adults with intellectual disabilities: generic or
      specialist units?
AB  - BACKGROUND: When adults with intellectual disabilities (ID) require a psychiatric
      admission, general adult mental health units are often used. Specialist units
      have emerged recently as a care option but there is only limited evidence of
      their effectiveness. Thus this study aims to describe and evaluate the
      effectiveness of a specialist inpatient unit and report on the utilization of
      generic and specialist inpatient services. METHOD: All patients admitted to a
      specialist ID psychiatric unit were evaluated on admission and immediately after
      discharge on a number of outcome measures. In addition, they were compared with
      those admitted to general adult mental health units covering the same catchment
      area. RESULTS: Significant improvements were demonstrated within the specialist
      unit cohort on measures including psychopathology, global level of functioning,
      behavioural impairment and severity of mental illness. The specialist unit
      patients had a longer length of inpatient stay but were less likely to be
      discharged to out-of-area residential placement. CONCLUSIONS: Specialist units
      are an effective care option for this group of people.

PMID- 14675227
TI  - Psychiatric diagnosis in persons with intellectual disability in India.
AB  - BACKGROUND: This study examines the rate of psychiatric diagnosis as per ICD-10
      and Reiss Screen for Maladaptive Behaviours (RSMB), and distribution of
      psychiatric diagnosis with regard to the severity of intellectual disability
      (ID). It also explores the degree of agreement between Reiss screen and clinical
      diagnosis (ICD-10) in relation to dual diagnosis. METHODS: In this study
      Intelligence (IQ) and Social Quotient (SQ) were estimated on Indian adaptation of
      Binet's scale and Vineland Social Maturity Scales, respectively, in 60
      consecutive persons with ID. Both ICD-10 and RSMB were used independently to
      determine the presence of psychiatric diagnosis. RESULTS: Clinically, according
      to ICD-10, about 60% of the sample was found to have dual diagnosis as compared
      to 48% on RSMB. Agreement between ICD-10 and RSMB about psychiatric comorbidity
      was 82%. Commonest psychiatric diagnosis was unspecified psychosis followed by
      bipolar affective disorders. CONCLUSION: Persons with ID do suffer from various
      psychiatric disorders. RSMB is a useful tool for differentiating between
      psychiatric problems and maladaptive behaviours. Hence RSMB can be used in the
      Indian context.

PMID- 14675228
TI  - Assessing the needs of people with learning disabilities and mental illness:
      development of the Learning Disability version of the Cardinal Needs Schedule.
AB  - BACKGROUND: People with learning disability (LD) experience a range of mental
      health problems. They are a complex population, whose needs are not well
      understood. This study focuses on the development of a systematic process of
      needs assessment for this population. METHODS: The Cardinal Needs Schedule used
      in general psychiatry was adapted for people with learning disabilities (LD). The
      Learning Disability version of the Cardinal Needs Schedule (LDCNS) was tested on
      a sample of 35 people with LD and mental illness for its inter-rater reliability.
      RESULTS: The inter-rater reliability (Kappa) was calculated for 22 areas of
      functioning assessed by the LDCNS. Overall, there was very good agreement in
      seven areas, moderate agreement in six areas, fair agreement in three areas and
      poor agreement in one area. In four areas of functioning, Kappa could not be
      calculated. More needs were found in the social domain than in the clinical
      domain. CONCLUSION: A systematic needs assessment schedule (LDCNS) was developed
      for people with LD and mental illness. The inter-rater reliability is generally
      acceptable, but requires further examination.

PMID- 14675229
TI  - Screening for psychiatric symptoms: PAS-ADD Checklist norms for adults with
      intellectual disabilities.
AB  - BACKGROUND: The Psychiatric Assessment Schedule for Adults with Developmental
      Disabilities Checklist (PAS-ADD Checklist) is a screening instrument designed to
      help carers recognize likely mental health problems in people with intellectual
      disabilities (ID). To date there are no published PAS-ADD Checklist data on a
      large nonpsychiatric population of adults with ID, an important step towards
      developing norms for comparative purposes. METHODS: Informants who had known
      participants for a median 24 months completed the PAS-ADD Checklist on 1155
      adults with ID living in community, residential care and hospital settings in a
      county district in the North-east of England. RESULTS: Normative data were
      obtained for the PAS-ADD Checklist for the study population with reference to
      gender, age, and type of residence. The overall prevalence of mental health
      problems was 20.1%, and the rates for affective/neurotic, organic and psychotic
      disorders were 14%, 3.9%, and 10.2%, respectively. Significant differences in the
      rates for particular disorders were found across gender, age and, residence type.
      CONCLUSIONS: The rates of mental disorders found in the study population were
      consistent with previous studies of general populations of people with ID using
      over-inclusive screening instruments. The PAS-ADD Checklist appears to be an easy
      to-use and sensitive tool for identifying mental health cases in ID populations,
      but further investigation is required concerning the specificity of the
      instrument.

PMID- 14675230
TI  - Life events and psychiatric symptoms in adults with intellectual disabilities.
AB  - BACKGROUND: Previous research has indicated that children and adults with
      intellectual disabilities (ID) may respond to traumatic and other life events in
      a similar way to the general population. However, few studies have charted the
      extent of exposure to recent life events in samples of adults with ID and the
      association of such exposure with general psychiatric problems. METHODS: Adults
      with ID (n = 1155) in community and residential services in a county district in
      North-east England were assessed using the Psychiatric Assessment for Adults with
      Developmental Disabilities Checklist (PAS-ADD Checklist), which includes a
      checklist of recent life events. Data were provided by informants who knew the
      index client well. RESULTS: Within the 12 months before data collection, the five
      most frequently experienced life events were: moving residence (15.5% of sample),
      serious illness of close relative or friend (9.0%), serious problem with close
      friend, neighbour or relative (8.8%), serious illness or injury to self (8.5%),
      and death of close family friend or other relative (8.3%). Overall, 46.3% had
      experienced one or more significant life events in the previous 12 months and
      17.4% had experienced two or more. Logistic regression analysis revealed that the
      presence of one or more life events in the previous 12 months added significantly
      to the classification of psychiatric caseness predicted by demographic variables
      (age, sex, residence in community or hospital) on the PAS-ADD Affective Disorder
      scale. Overall, the odds ratio for affective disorder given exposure to one or
      more life events was 2.23 [95% confidence interval (CI) = 1.56, 3.18].
      CONCLUSIONS: Small, but potentially significant relationships were found between
      life events exposure and psychiatric problems in adults with ID. Further research
      is needed to explore the causal direction of this relationship and also to
      develop more sensitive measures of life events relevant to the situation of
      adults in residential and community service environments.

PMID- 14675231
TI  - Behavioural and emotional disturbances in people with Prader-Willi Syndrome.
AB  - BACKGROUND: The study of the behaviour profile in subjects with Prader-Willi
      Syndrome (PWS). METHODS: A total of fifty-eight 3- to 29-year-old subjects with
      PWS were studied using a standardized parent report of behavioural and emotional
      disturbances. RESULTS: There was an increase of behavioural and emotional
      disturbances for the adolescent and young adult age range, whereas gender and
      intelligence were not significant. Increasing body mass index (BMI) was also
      associated with more behavioural and emotional disturbances. There was no
      significant relation between genetic status and behavioural abnormalities.
      CONCLUSIONS: This systematic study supports single case observations of a
      heightened psychiatric vulnerability of adolescent and young adult PWS subjects.

PMID- 14675232
TI  - Using the Diagnostic Assessment of the Severely Handicapped-II (DASH-II) to
      measure the therapeutic effects of risperidone.
AB  - BACKGROUND: Within the scope of a double-blind, placebo-controlled, crossover
      medication study, the Diagnostic Assessment of the Severely Handicapped-II (DASH
      II) was evaluated as a measurement for determining the effectiveness of the
      medication risperidone in treating the problem behaviour of 21 people with
      intellectual disabilities (ID). METHOD: Participants' caregivers completed the
      DASH-II during the placebo/baseline phase of the study and the maintenance phase
      of the study, and completed the Aberrant Behavior Checklist - Community (ABC-C)
      weekly throughout the entire study. The results obtained using the DASH-II were
      compared to those obtained using the ABC-C, an instrument shown to be well
      correlated with the DASH-II. RESULTS: Results suggest that while the DASH-II and
      the ABC-C were well correlated during the placebo/baseline phase of the current
      study, they were not well correlated at completion of the 6-month maintenance
      phase of the medication trial. CONCLUSION: The DASH-II, while appropriate for
      assisting in the diagnosis of psychopathology in people with ID, does not appear
      to monitor changes in problem behaviour as a result of risperidone use as well as
      the ABC-C. Differences in the frequency of problem behaviour that each measure
      evaluated and the applicability of using the DASH-II to measure medication
      effects on problem behaviour are discussed.

PMID- 14675233
TI  - Formal versus informal interventions for challenging behaviour in persons with
      intellectual disabilities.
AB  - BACKGROUND: Although effective, humane treatments exist for persons with
      intellectual disabilities (ID) who have challenging behaviour, little research
      has examined the extent to which clients receive formal, documented vs.
      undocumented interventions. METHODS: Caregivers (of 625 persons with ID living in
      community and institutional residences in Ontario, Canada) were interviewed to
      examine the prevalence of different types of interventions. RESULTS: Overall, 55%
      of the 2506 different interventions (for 1464 target behaviours) were informal
      (i.e. lacking documented input from a professional, written intervention plans,
      and systematic evaluation). No significant differences emerged on formality of
      intervention across participant gender, age, level of ID, and type of residence.
      There were significantly more informal than formal behavioural interventions and
      counselling/psychotherapy, and no significant difference in the overall
      prevalence of formal and informal intrusive procedures. Behaviour control
      medications were paired more often with formal (67%) than informal interventions
      for dangerous behaviours. Formal interventions were associated with higher
      caregiver-reported estimates of behavioural improvement, higher inter-rater
      agreement on the descriptions of an individual client's target behaviours and
      interventions, and more caregiver training and supervision. CONCLUSIONS: The low
      levels of intervention accountability, training and supervision may place many
      clients with challenging behaviour at increased risk for ineffective and
      unnecessary restrictive interventions, and physical abuse. The results of this
      survey stimulated the government to write province-wide standards (that have yet
      to be implemented).

PMID- 14675234
TI  - Offenders with intellectual disability: a prospective comparative study.
AB  - BACKGROUND: Intellectually disabled offenders (IDO) are a poorly served and under
      recognized group, who are likely to require long-term specialist treatments and
      interventions. METHOD: This prospective study investigated the characteristics
      and factors that influence outcome in this group, with particular reference to
      therapeutic interventions. Sixty-one individuals were identified from contact
      with either (1) specialist health and social services for people with
      intellectual disability (ID) or (2) nonspecialist services in the criminal
      justice or (forensic) mental health/social service systems. The participants were
      assessed at baseline and after a mean of 10 months in order to compare recidivism
      rates and the impact of therapeutic interventions. RESULTS: The findings suggest
      that IDO start offending at an early age, that they frequently have a history of
      multiple offences, and that sex offending and arson are over-represented offence
      types. Those participants recruited from nonspecialist ID services had
      significantly higher IQs and were less likely to have had contact with community
      social and health support agencies. Despite the high rates of psychopathology,
      there was little evidence for efficacy of therapeutic interventions, which, where
      offered, appeared to be of a nonspecific nature. At second interview,
      approximately half of the sample had re-offended.

PMID- 14675235
TI  - Subclinical hepatic encephalopathy: elusive 'gold standard'.

PMID- 14675236
TI  - Therapeutic options for esophageal cancer.
AB  - Options for the treatment of esophageal cancer used to be very limited, with
      surgical resection and radiotherapy methods aimed at both cure or palliation,
      and, in those unfortunate patients with severe dysphagia, intubation with a
      plastic prosthesis to restore esophageal luminal patency. Progress in the
      management of this cancer in the past two decades includes refinement in surgical
      techniques and perioperative care, better radiological staging methods, enhanced
      means of planning and delivering radiotherapy, multimodality treatments, and
      better designs in esophageal prosthesis. For individual patients, a stage
      directed therapeutic plan can be used. Long-term survival, however, remains
      suboptimal for this deadly disease. The current review presents an overview of
      the commonly employed therapeutic options for esophageal cancer at the beginning
      of the 21st century.

PMID- 14675237
TI  - Which types of non-bleeding visible vessels in gastric peptic ulcers should be
      treated by endoscopic hemostasis?
AB  - BACKGROUND AND AIMS: Because non-bleeding visible vessels (NBVV) of gastric
      peptic ulcers have the potential to re-bleed, endoscopic hemostatic treatment may
      be necessary during the first emergency endoscopy. However, not all NBVV re
      bleed, and endoscopic hemostasis sometimes causes fatal side-effects. Therefore,
      we have evaluated the risk of re-bleeding from various NBVV in gastric peptic
      ulcers to determine which types should be treated by endoscopy to prevent re
      bleeding. METHODS: A total of 227 NBVV in 202 patients with gastric peptic ulcers
      that were endoscopically followed without endoscopic hemostatic procedures were
      classified by the following factors: vessel color, form, location of the NBVV in
      the ulcer crater, and location of the ulcer in the stomach. The re-bleeding rate
      was then analyzed for each type of NBVV. RESULTS: Significantly high rates of re
      bleeding were observed in cases with white, protruded and peripheral NBVV. In
      particular, white NBVV located in the peripheral zone of the ulcer crater were
      frequent re-bleeding sources. The location of the ulcer in the stomach was not a
      statistically significant factor in determining re-bleeding rates. CONCLUSION: We
      found that white, protruded and peripherally located NBVV in gastric ulcers have
      a higher chance of re-bleeding if preventive endoscopic hemostatic procedures are
      not performed.

PMID- 14675238
TI  - Expression of Mg2+-dependent, HCO3- -stimulated adenine triphosphatase in the
      human duodenum.
AB  - BACKGROUND AND AIM: Mg2+-dependent, HCO3- -stimulated adenine triphosphatase
      (Mg2+-HCO3- -ATPase) is an enzyme that catabolizes ATP in the presence of HCO3-
      and Mg2+. The activity of this ATPase is known to be present in the duodenum, but
      its physiological role remains unclear. In the present study, the aim was to
      study the distribution and biochemical profiles of Mg2+-HCO3- -ATPase in the
      human duodenum. METHODS: The histochemistry of Mg2+-HCO3- -ATPase, its
      localization using electron microscopy (EMS), and the measurement of enzyme
      activity were carried out by using mucosal samples of the bulb, and the second
      and third portions of the duodenum, obtained from six volunteers by endoscopic
      biopsy. RESULTS: The Mg2+-HCO3- -ATPase was detected in the brush border along
      the luminal surface of human duodenal epithelial cells. The EMS confirmed its
      localization to the surface of microvilli. The activity of Mg2+-HCO3- -ATPase was
      higher in the distal portions of the human duodenum than in the bulb. Its maximal
      activity was obtained under a pH of 8.5, and in the presence of 1.0 mmol/L MgCl2
      and 50 mmol/L NaHCO3, but the activity was undetectable in pH <7.4 or >9.5.
      CONCLUSION: The results of the present study suggested that Mg2+-HCO3- -ATPase
      may work for luminal alkalization in the distal portions of the human duodenum
      and may contribute to maintaining the activity of pancreatic digestive enzymes.

PMID- 14675239
TI  - Three different subsite classification systems for carcinomas in the proximity of
      the GEJ, but is it all one disease?
AB  - BACKGROUND AND AIM: Currently there are three different subsite classification
      systems for carcinomas in the region of the gastroesophaeal junction (GEJ),
      namely ICD-O, Munich and Liverpool. The aim of the present study was to compare
      clinicoepidemiological, pathological and molecular features of adenocarcinomas in
      the proximity of the GEJ, classified according to their position with respect to
      the GEJ initially, and then classified according to ICD-O, Munich and Liverpool
      classifications. METHODS: Forty-seven adenocarcinomas in the proximity of the GEJ
      were subdivided into groups 1 (exclusively within esophagus), 2 (mainly within
      esophagus but extending distally across GEJ), 3 (equally present in esophagus and
      stomach) or 4 (mainly in stomach but extending proximally across GEJ), and
      analysis of their clinicoepidemiological, pathological and molecular features was
      performed. Molecular characterization included loss of heterozygosity (LOH) and
      microsatellite instability analyses. RESULTS: Group 3 carcinomas were younger
      than other carcinomas in the proximity of the GEJ, but otherwise these carcinomas
      were similar in their clinicoepidemiological, pathological and molecular
      features. There were no significant differences between esophageal (groups 1 and
      2) and gastric (groups 3 and 4) carcinomas as classified by ICD-O. Munich types I
      (groups 1 and 2), II (group 3) and III (group 4) carcinomas of the GEJ were also
      similar. LOH at the site of the Rb tumor suppressor gene and at 17p11.1-p12 was
      more common in GEJ (groups 2, 3 and 4) than lower third (group 1) esophageal
      carcinomas classified according to the Liverpool system. CONCLUSION: Overall,
      adenocarcinomas of the lower esophagus and adenocarcinomas involving the GEJ have
      similar clinicoepidemiological, pathological and molecular features no matter
      which subsite classification is used, adding further evidence that they represent
      the same disease.

PMID- 14675240
TI  - Five-lipoxygenase-activating protein inhibitor MK-886 induces apoptosis in
      gastric cancer through upregulation of p27kip1 and bax.
AB  - BACKGROUND AND AIM: Products of the arachidonic acid metabolizing enzyme, 5
      lipoxygenase (5-LOX), stimulate the growth of several cancer types. Inhibitors of
      5-LOX and 5-LOX-activating protein (FLAP) induce apoptosis in some cancer cells.
      Here, the authors investigated the effect of a FLAP inhibitor, MK-886, on the
      inhibition of proliferation and induction of apoptosis in gastric cancer.
      METHODS: Cell proliferation in gastric cancer cells was measured using an 3-(4,5
      dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Apoptosis was
      measured using acridine orange staining and flow cytometry. Protein expression of
      apoptosis-related genes p53, p21waf1, p27kip1, bcl-2 families, cytochrome c, and
      the caspases were examined using Western blotting. Caspase-3 activity was
      measured using colorimetric assay of substrate cleavage. RESULTS: MK-886
      inhibited cell growth in a dose- and time-dependent manner. Apoptosis was induced
      in gastric cancer cells and was characterized by upregulation of p27kip1 and bax,
      with release of cytochrome c from mitochondria into cytosol, which initiated
      caspase-3 activation. Specific caspase-3 inhibitors partially blocked MK-886
      induced apoptosis. CONCLUSION: The present results suggest that MK-886 induces
      apoptosis in gastric cancer cells through upregulation of p27kip1 and bax, and
      that MK-886 is a potentially useful drug in gastric cancer prevention and
      therapy.

PMID- 14675241
TI  - Cost-effectiveness of colorectal cancer screening: comparison of community-based
      flexible sigmoidoscopy with fecal occult blood testing and colonoscopy.
AB  - BACKGROUND AND AIMS: To determine the cost-effectiveness of screening for
      colorectal cancer using flexible sigmoidoscopy once every 10 years, compared with
      annual and biennial rehydrated Hemoccult fecal occult blood testing and
      colonoscopy once every 10 years, or no screening. METHODS: A Markov model was
      developed in order to simulate the progression of a cohort of asymptomatic,
      average-risk individuals aged 55-64 years who were moving through a defined
      series of states towards death. The main outcome measures were: cases of
      colorectal cancer averted, colorectal cancer deaths averted, and cost per life
      year saved. RESULTS: Colonoscopy averted the greatest number of cases of
      colorectal cancer (35%), followed by flexible sigmoidoscopy (25%), and annual
      (24%) and biennial (14%) fecal occult blood testing. Colonoscopy averted the
      greatest number of deaths from colorectal cancer (31%), followed by annual fecal
      occult blood testing (29%), flexible sigmoidoscopy (21%) and biennial fecal
      occult blood testing (19%). Flexible sigmoidoscopy was the most efficient in
      terms of cost per life-year saved (16,801 Australian dollars), followed by
      colonoscopy (19,285 Australian dollars), biennial (41,183 Australian dollars),
      and annual (46,900 Australian dollars) fecal occult blood testing. CONCLUSIONS:
      Flexible sigmoidoscopy and colonoscopy are cost-effective strategies for reducing
      the disease burden of colorectal cancer.

PMID- 14675242
TI  - New indication for endoscopic treatment of colorectal carcinoma with submucosal
      invasion.
AB  - BACKGROUND AND AIMS: Although an increasing number of early colorectal cancers
      (CRC) have been curatively treated by endoscopy, there have been no definitive
      criteria to decide the effectiveness of such therapy. We retrospectively analyzed
      clinicopathological factors to establish criteria for curative endoscopic
      treatment of early CRC. METHODS: First, risk factors of lymph node metastasis
      were analyzed in 171 patients who received surgery with postoperative histology
      of CRC submucosal invasion. The resultant new criteria were evaluated in another
      60 patients who experienced endoscopic resection of CRC and surgery according to
      the current criteria most often used in Japan. RESULTS: In the first substudy,
      lymph node metastasis was present in 18 of 171 patients (10.5%). Lymphatic
      permeation, sprouting and infiltrative growth of cancer cells were identified as
      histological factors significantly related to lymph node metastasis, and observed
      in much higher rates when the depth of submucosal invasion was beyond 1,500
      micron. The minimum depth with positive lymph nodes was 1,075 micron. In the
      second group of 60 patients, lymph node metastasis was recorded in none of nine
      patients who met our new criteria of complete endoscopic treatment: submucosal
      invasion below 1,500 micron in depth, and no lymphatic permeation, sprouting or
      infiltrative growth pattern on tumor histology. Lymph node metastasis was
      positive in three of the other cases who did not meet our new criteria.
      CONCLUSIONS: The present study showed that endoscopic treatment of early CRC may
      be considered complete when submucosal invasion beyond 1,500 micron, lymphatic
      permeation, sprouting, and infiltrating growth are all denied.

PMID- 14675243
TI  - Randomized comparative study of surgical adjuvant chemotherapy using 5
      fluorouracil and dl-leucovorin with CDDP, 5-FU and dl-leucovorin for advanced
      colorectal cancer.
AB  - BACKGROUND: 5-fluorouracil (5-FU) is the most useful chemotherapeutic agent for
      colorectal carcinoma. Recently, the effectiveness of multidrug therapy in
      modifying the anticancer activity of 5-FU for advanced cases was clarified. We
      conducted a randomized comparative study of surgical adjuvant chemotherapy
      comparing cis-diamminedichloroplatinum (CDDP), 5-FU and dl-leucovorin (LV) (PFL
      therapy) with dl-LV and 5-FU (FL therapy) in patients who underwent curative
      resection of stage II and III colorectal carcinoma. METHODS: Thirty-one patients,
      13 ungergoing PFL therapy and 18 undergoing FL therapy, completed the scheduled
      administration, while 20 dropped out. Administration schedules were as follows:
      PFL therapy consisted of 13 mg/m2 CDDP, 300 mg/m2 5-FU and 30 mg/body weight LV
      for 5 consecutive days. The FL therapy consisted of 300 mg/m2 5-FU and 30 mg/body
      weight LV for 5 consecutive days in hospital. Both regimens were followed by
      biweekly administration of the same dosages of LV and 5-FU in an outpatient
      setting. RESULTS: Seven of 23 patients in the PFL therapy group and five of 28
      patients in the FL therapy group experienced recurrence of colorectal carcinomas.
      Regarding prognosis of stage II patients, both groups showed similar results in 5
      year disease specific survival and disease-free survival. However, stage III
      patients obtained better prognostic results in the FL therapy group than in the
      PFL therapy group. Major toxicities in these regimens were vomiting and
      leukopenia, both being more frequent in the PFL therapy group. Symptoms of
      toxicity resolved completely in all patients. CONCLUSION: From the present study
      we found that PFL therapy brought no benefit for stage II and III colorectal
      carcinoma compared with FL therapy. We should search for more appropriate
      adjuvant therapy, increasing the therapeutic effect of 5-FU + LV for stage II and
      III colorectal carcinoma.

PMID- 14675244
TI  - Wireless capsule endoscopy: experience in a tropical country.
AB  - BACKGROUND AND AIM: Capsule endoscopy is fast becoming the procedure of choice
      for small bowel imaging, especially to investigate the cause of unexplained
      gastrointestinal (GI) bleeding. We report our experience with capsule endoscopy
      in 24 cases with various indications. METHODS: In patients with unexplained GI
      bleeding or chronic anemia, the cause could be established in nine of 12 cases
      (75%), which included angioectasiae, leiomyomata and parasitic infestation.
      RESULTS: The yield of capsule endoscopy was highest in patients presenting with
      chronic diarrhea and suspicion of small bowel mucosal disease, where Crohn's
      disease and tuberculosis could be diagnosed. However, in patients with
      unexplained abdominal pain, capsule endoscopy was found to be least useful
      because 5/7 patients in the study were normal, emphasizing the importance of case
      selection. Overall, capsule endoscopy yielded a positive diagnosis in 16 of the
      24 cases (66.6%). CONCLUSIONS: The experience of capsule endoscopy in a tropical
      clinical setting is no different from elsewhere, although certain conditions like
      worm infestation are more likely to be detected in this environment.

PMID- 14675245
TI  - Age as a predictor of hyperphosphatemia after oral phosphosoda administration for
      colon preparation.
AB  - BACKGROUND AND AIM: It has been reported that oral phosphosoda (OPS), commonly
      used in bowel cleansing, may cause complications such as hyperphosphatemia and
      hypocalcemia. This has been observed in patients with normal kidney function and
      in those with renal insufficiency. Few controlled studies have been performed
      with respect to age on healthy subjects after OPS administration. METHODS:
      Seventy patients (38 men and 32 women; mean age 47 +/- 12 years, range 25-80
      years) were enrolled in the present study. Half of the 90 mL total volume of OPS
      was ingested 18 h before colonoscopy, and the other half 6 h before the
      procedure. Creatinine clearance rate (CCR) and serum levels of sodium, potassium,
      calcium and phosphate were measured before and after OPS administration. RESULTS:
      After OPS administration, serum calcium and potassium were significantly lower (P
      < 0.05), and serum phosphate and sodium were significantly higher than
      pretreatment levels (P < or = 0.01). The statistically significant changes in
      serum sodium, potassium and calcium were within normal laboratory ranges. The
      mean change in serum phosphate was positively correlated with age (Pearson's r =
      0.705; p < 0.001). CONCLUSION: Administration of OPS causes a significant rise in
      serum phosphate, even in patients with normal CCR. The elevation is significantly
      greater in elderly patients. Administration of OPS can be considered safe for
      young and middle-aged patients with normal renal function; however, it should be
      used with caution in elderly patients, even in those with normal CCR and serum
      creatinine values.

PMID- 14675246
TI  - Systemic, portal and renal effects of terlipressin in patients with cirrhotic
      ascites: pilot study.
AB  - BACKGROUND AND AIM: Terlipressin is a vasopressin analog that may improve renal
      function in hepatorenal syndrome by mechanisms as yet unknown. The authors
      investigated the effect of the drug on systemic, hepatic and renal hemodynamics
      in cirrhosis. METHODS: Six patients with cirrhosis and ascites were studied (five
      Child's B and one Child's C). Heart rate (HR), mean arterial pressure (MAP),
      cardiac output (CO), systemic vascular resistance (SVR), hepatic venous pressure
      gradient (HVPG), reverse thermodilution unilateral real-time renal blood flow
      (RBF), urinary flow, and sodium concentrations were measured before and 1 h after
      an intravenous bolus of 2 mg of terlipressin. RESULTS: Following terlipressin
      administration, HR fell significantly (84.2 +/- 6 to 70.8 +/- 4.9, P = 0.013),
      MAP increased (72.7 +/- 3.6 to 87 +/- 5.3 mmHg, P = 0.027), CO fell (7.4 +/- 0.8
      to 6.4 +/- 0.8 L/min, P = 0.02) and SVR increased (1368.5 +/- 236 to 2079.7 +/-
      458, P = 0.04). There were no significant differences in HVPG (12.3 +/- 1.6 to 14
      +/- 0.9 mmHg, P-value not significant [NS]), RBF (255 +/- 0.02 compared with 249
      +/- 0.02 mL/min, P-value NS), urinary volume (49.1 +/- 8.9 compared with 49.6 +/-
      16.7 mL/ h, P-value NS) and urinary sodium excretion (4 +/- 1.1 compared with 5.9
      +/- 3.5 mmol/ h). CONCLUSION: In the present small study, the authors were able
      to demonstrate that a bolus injection of terlipressin produced an increase in MAP
      and SVR, along with a reduction in cardiac output without a reduction in renal
      blood flow. Further studies are necessary to define the effects of terlipressin
      on renal hemodynamics and sodium excretion.

PMID- 14675247
TI  - Digital quantification of fibrosis in liver biopsy sections: description of a new
      method by Photoshop software.
AB  - BACKGROUND: The precise quantification of fibrous tissue in liver biopsy sections
      is extremely important in the classification, diagnosis and grading of chronic
      liver disease, as well as in evaluating the response to antifibrotic therapy.
      Because the recently described methods of digital image analysis of fibrosis in
      liver biopsy sections have major flaws, including the use of out-dated techniques
      in image processing, inadequate precision and inability to detect and quantify
      perisinusoidal fibrosis, we developed a new technique in computerized image
      analysis of liver biopsy sections based on Adobe Photoshop software. METHODS: We
      prepared an experimental model of liver fibrosis involving treatment of rats with
      oral CCl4 for 6 weeks. After staining liver sections with Masson's trichrome, a
      series of computer operations were performed including (i) reconstitution of
      seamless widefield images from a number of acquired fields of liver sections;
      (ii) image size and solution adjustment; (iii) color correction; (iv) digital
      selection of a specified color range representing all fibrous tissue in the image
      and; (v) extraction and calculation. RESULTS: This technique is fully
      computerized with no manual interference at any step, and thus could be very
      reliable for objectively quantifying any pattern of fibrosis in liver biopsy
      sections and in assessing the response to antifibrotic therapy. It could also be
      a valuable tool in the precise assessment of antifibrotic therapy to other tissue
      regardless of the pattern of tissue or fibrosis.

PMID- 14675248
TI  - Absence of hemochromatosis associated Cys282Tyr HFE gene mutation and low
      frequency of hemochromatosis phenotype in nonalcoholic chronic liver disease
      patients in India.
AB  - BACKGROUND AND AIM: Hereditary hemochromatosis (HHC) is an autosomal recessive
      disorder causing primary iron overload syndrome and chronic liver disease (CLD).
      This genetic disease is commonly associated with C282Y mutation of the HFE gene,
      commonly seen in the Northern European population. Minor reports on HHC are
      available from Asia, however, so far no genetic study is available from India. We
      prospectively studied the prevalence of C282Y mutation in CLD patients and
      healthy subjects in a tertiary care referral center in India. METHODS: A total of
      249 consecutive biopsy proven CLD (HBV = 112, HCV = 72, cryptogenic = 65)
      patients and 134 age matched healthy controls were included. Cases of secondary
      iron overload, pregnancy, chronic alcoholism, age < 30 years and hepatocellular
      carcinoma (HCC) were excluded. A transferrin saturation index (TSI) of >60% was
      suggestive of a phenotypic presentation of HHC. C282Y mutation was studied by
      restriction fragment length polymorphism (RFLP) using genomic DNA. The 387 bp
      fragment obtained after polymerase chain reaction was digested with 10 units of
      endonuclease Rsa1. The mutation was detected by creation of an additional
      restriction site, giving rise to fragments of 247 111 and 29 bp. RESULTS: While
      the mean TSI was comparable, serum ferritin was significantly higher in CLD
      patients compared to controls (38 +/- 16%vs 28 +/- 13%; p = not significant (NS),
      and 125 +/- 18 vs 42 +/- 25 ng/mL; p < 0.001). A TSI of >60% was detected in 24
      (9.64%) patients. Only one restriction site was found for endonuclease Rsa1,
      giving rise to two fragments of 247 and 140 bp, suggesting absence of C282Y
      mutation in the HFE gene in all patients. CONCLUSIONS: Almost 10% of nonalcoholic
      CLD patients in India have iron overload, but this is independent of C282Y
      mutation of the HFE gene. Large population based studies are recommended to
      investigate the prevalence of this rare disorder in India.

PMID- 14675249
TI  - Hepatic stellate cells in hepatitis C patients: relationship with liver iron
      deposits and severity of liver disease.
AB  - BACKGROUND AND AIM: To determine the relationship between hepatic stellate cell
      (HSC) populations and severity of liver disease and liver iron deposits in
      patients with chronic hepatitis C virus (HCV). We also studied the relationship
      between iron cellular distribution and HSC population and the role of HFE
      mutations in the determination of iron deposits. METHODS: Forty-nine chronic HCV
      patients with varying degrees of liver damage and liver iron deposits were
      studied. A liver biopsy was scored for histology activity index (HAI), fibrosis
      and iron deposits. The number of HSC in the liver was evaluated by an
      immunohistochemical double-staining method to identify glial fibrillary acid
      protein (GFAP) and smooth muscle alpha-actin (alpha-SMA). RESULTS: The HSC
      population was significantly higher in HCV patients than in normal controls and
      was predominant in zones 1 and 3. Liver iron deposits were observed in 49% of
      patients and were mild/moderate in most cases. We found a significantly higher
      number of GFAP and alpha-SMA positive cells in patients with liver iron deposits
      compared with those without iron deposits, and a positive correlation between
      liver iron scores and number (%) of GFAP and alpha-SMA positive cells. We
      observed a significantly higher number of GFAP and alpha-SMA positive cells in
      moderate/severe hepatitis than in minimal/mild hepatitis, and a positive
      correlation between GFAP and alpha-SMA positive cells and HAI and fibrosis
      scores. CONCLUSIONS: Liver iron deposits in chronic HCV are common and are
      associated with activation of HSC. Thus, even mild iron deposits might stimulate
      HSC and contribute to liver damage.

PMID- 14675250
TI  - Evaluation of the hepatic reduction of a nitroxide radical in rats receiving
      ascorbic acid, glutathione or ascorbic acid oxidase by in vivo electron spin
      resonance study.
AB  - BACKGROUND: A nitroxide radical, 4-hydroxyl-2,2,6,6-tetramethylpiperidin-1-oxyl
      (TEMPOL), is directly reduced to hydroxylamine by ascorbic acid (AsA). Ascorbic
      acid is oxidized to dehydroascorbic acid (DHA) by ascorbic acid oxidase (AAOx),
      and DHA is reduced to AsA by glutathione (GSH). In the present study, in vivo and
      ex vivo reduction of TEMPOL in the rat liver under various conditions of AsA
      supply was investigated using an electron spin resonance (ESR) spectrometer
      equipped with a surface coil-type resonator. METHODS: To investigate in vivo
      hepatic reduction of TEMPOL, an ESR study of the liver of living rats which
      orally received AsA or intravenously received GSH or AAOx was made. To
      investigate direct interactions between TEMPOL and GSH or AAOx, an in vitro ESR
      study was conducted. To investigate TEMPOL reduction in the hepatic homogenate,
      an ex vivo ESR study was performed. RESULTS: Ascorbic acid and GSH administration
      increased the in vivo hepatic reducing ability of TEMPOL. In contrast, AAOx
      administration decreased the reducing ability. In vitro TEMPOL was not reduced by
      GSH and hydroxylamine was not oxidized by AAOx. Reducing ability in the hepatic
      homogenate of AAOx-treated rats decreased, but that for GSH-treated rats was
      unchanged. CONCLUSION: Ascorbic acid administration directly increases hepatic
      reducing ability. Ascorbic acid, which increased in the plasma due to GSH
      administration, entered the liver and enhanced the hepatic reducing ability.
      Administration of AAOx impaired the hepatic reducing ability by oxidizing AsA in
      the plasma and/or the liver.

PMID- 14675251
TI  - Images of interest. Gastrointestinal: gastrointestinal bezoars.

PMID- 14675252
TI  - Images of interest. Hepatobiliary and pancreatic: hepatic congestion with
      varicocele.

PMID- 14675253
TI  - Hepatic hydropericardium.
AB  - A 41-year-old man with chronic hepatitis C and cirrhosis presented with
      pericardial effusion and tamponade requiring pericardiocentesis. Nine liters of
      pericardial fluid was drained with complete resolution of his ascites. He
      represented with recurrent pericardial effusions despite salt restriction and
      diuretic therapy. Subsequent radionuclide scans demonstrated a direct connection
      between the peritoneal and pericardial spaces. A pericardial window was formed
      but despite this there was recurrence of pericardial effusion and pleural
      effusion. The patient underwent orthotopic liver transplantation 7 months later
      and no recurrence of pleural or pericardial effusion was observed following
      transplantation. We believe this is the first case report of pericardial effusion
      secondary to cirrhotic ascites and a communication between the peritoneal and
      pericardial cavities.

PMID- 14675254
TI  - Unique clinicopathological features of patients with primary malignant hepatic
      tumors who are seropositive for lectin-reactive alpha-fetoprotein alone: report
      of five cases.

PMID- 14675255
TI  - Wilson's disease with coexisting autoimmune hepatitis.

PMID- 14675256
TI  - Effect of octreotide and corticosteroids on human sphincter of oddi motility.

PMID- 14675257
TI  - Oleylethanolamide: a lipid mediator involved in gut satiety mechanisms.

PMID- 14675258
TI  - Liver transplantation in an endostage cirrhosis patient with abdominal
      compartment syndrome following a spontaneous rectus sheath hematoma.

PMID- 14675259
TI  - Quality of life of women living with hepatitis C.

PMID- 14675260
TI  - Pathogenesis and management of alcoholic hepatitis.
AB  - Alcoholic hepatitis is a potentially life-threatening complication of alcoholic
      abuse, typically presenting with symptoms and signs of hepatitis in the presence
      of an alcohol use disorder. The definitive diagnosis requires liver biopsy, but
      this is not generally required. The pathogenesis is uncertain, but relevant
      factors include metabolism of alcohol to toxic products, oxidant stress,
      acetaldehyde adducts, the action of endotoxin on Kupffer cells, and impaired
      hepatic regeneration. Mild alcoholic hepatitis recovers with abstinence and the
      long-term prognosis is determined by the underlying disorder of alcohol use.
      Severe alcoholic hepatitis is recognized by a Maddrey discriminant function >32
      and is associated with a short-term mortality rate of almost 50%. Primary therapy
      is abstinence from alcohol and supportive care. Corticosteroids have been shown
      to be beneficial in a subset of severely ill patients with concomitant hepatic
      encephalopathy, but their use remains controversial. Pentoxifylline has been
      shown in one study to improve short-term survival rates. Other pharmacological
      interventions, including colchicine, propylthiouracil, calcium channel
      antagonists, and insulin with glucagon infusions, have not been proven to be
      beneficial. Nutritional supplementation with available high-calorie, high-protein
      diets is beneficial, but does not improve mortality. Orthotopic liver
      transplantation is not indicated for patients presenting with alcoholic hepatitis
      who have been drinking until the time of admission, but may be considered in
      those who achieve stable abstinence if liver function fails to recover.

PMID- 14675261
TI  - Chronic hepatitis B: a long-term retrospective cohort study of disease
      progression in Shanghai, China.
AB  - BACKGROUND AND AIMS: The present study aimed to describe the disease progression
      of chronic hepatitis B patients without or with compensated cirrhosis at
      baseline, to estimate the risk of progression to decompensated cirrhosis,
      hepatocellular carcinoma and death, and to determine prognostic factors of
      disease progression in patients in Shanghai, China. METHODS: Stored medical
      records from 322 biopsy-confirmed chronic hepatitis B cases diagnosed between
      1981 and 1993 were selected, and the status of patients was tracked in 1999-2000.
      Among consenting patients, ultrasound examination and laboratory tests were
      conducted. Person-year incidence rates, Kaplan-Meier analysis, log-rank tests,
      and Cox regression analysis were conducted. RESULTS: Among chronic hepatitis B
      patients without compensated cirrhosis, the incidence rates of decompensated
      cirrhosis, hepatocellular carcinoma, and death were 6.3, 2.8, and 7.6 per 1000
      person-years, respectively, while for patients with compensated cirrhosis, the
      rates were 35.6, 8.2, and 35.2 per 1000 person-years, respectively. The 15-year
      survival rate was 88% for patients without compensated cirrhosis, compared with
      56% for patients with compensated cirrhosis (P < 0.001). Cox regression analysis
      demonstrated that increased alpha-fetoprotein (AFP) (P < 0.01), gamma-globulin (P
      < 0.05), and high-level severity of hepatic fibrosis (P < 0.01) at baseline were
      risk factors of decompensated cirrhosis. Factors associated with a high risk of
      death included elevated AFP at baseline (P < 0.01), severity of hepatic fibrosis
      (P < 0.003), and sustained positivity for hepatitis B surface antigen (P <
      0.004). CONCLUSION: Increased AFP and severity of hepatic fibrosis at baseline
      were associated with higher risk of decompensated cirrhosis and death. These data
      provide rare empirical estimates of the negative long-term outcomes for patients
      with chronic hepatitis B in Shanghai, China.

PMID- 14675262
TI  - Evolution of wild type and mutants of the YMDD motif of hepatitis B virus
      polymerase during lamivudine therapy.
AB  - BACKGROUND AND AIM: Long-term lamivudine treatment for chronic hepatitis B virus
      (HBV) infection induces the emergence of lamivudine resistant HBV YMDD mutant
      strains. The aim of the present study was to observe the clone evolution of YMDD
      wild type and mutant strains in pretreatment and post-treatment samples during
      lamivudine therapy and analyze their clinical significance. METHODS: Ten serum
      samples (five before and five after 48 weeks of therapy) obtained from five
      patients chronically infected with HBV and treated with lamivudine were studied.
      Part of the HBV polymerase gene flanking the YMDD motif was sequenced after
      polymerase chain reaction (PCR) amplification. Meanwhile, 20-24 clones were
      selected at random from each sample and YMDD wild type and mutant strains were
      detected by real-time fluorimetry PCR established in our laboratory. RESULTS: The
      YMDD mutants were not detectable in all five patients before treatment and were
      found in four patients after 48 weeks of therapy by sequencing directly on PCR
      products. Analysis of individual clones showed that the ratios of mutant strains
      in each of the five patients were 0, 9.5, 0, 4.5 and 5.6%, respectively, before
      therapy and 100, 100, 65, 100 and 0%, respectively, after 48 weeks of therapy.
      M552I was detected before therapy in one patient but M552V became the domain
      strain after therapy. Until 52 weeks of therapy, serum HBV DNA and alanine
      aminotransferase (ALT) breakthrough were found in two of the four patients with
      YMDD mutations. The fifth patient experienced breakthrough of ALT but HBV DNA
      remained undetectable. CONCLUSIONS: The mutant strains of YMDD motif of HBV
      polymerase could be found in patients before lamivudine treatment, indicating
      that antiviral therapy allows the rapid selection of resistant strains. The
      replication ability of the M552V mutant strain might be stronger than that of the
      M552I mutant strain.

PMID- 14675263
TI  - Mechanisms of increased insulin resistance in non-cirrhotic patients with chronic
      hepatitis C virus infection.
AB  - BACKGROUND AND AIM: Evidence showing a higher prevalence of diabetes mellitus
      (DM) in patients with chronic hepatitis C virus (HCV) infection has been
      accumulating. However, the reason why chronic HCV infection promotes DM remains
      unknown. In the present study, the authors focused on non-cirrhotic and non
      diabetic patients with chronic HCV infection and evaluated the factors
      responsible for increases in insulin resistance. METHODS: Fifty-six patients
      diagnosed with HCV-related chronic liver disease were included. Biochemical
      information including body mass index (BMI), aspartate aminotransferase (AST),
      alanine aminotransferase, cholinesterase, triglyceride, total cholesterol,
      hemoglobin, platelet count, glycosylated hemoglobin, immunoreactive insulin
      (IRI), and serum levels of tumor necrosis factor (TNF)-alpha and HCV-RNA were
      determined using venous blood samples obtained from each patient after overnight
      fasting. Homeostasis model assessment of insulin resistance (HOMA-IR), a simple
      and convenient measure of insulin resistance, was also calculated. The
      relationship between the stage of liver fibrosis and HOMA-IR, and the clinical
      factors responsible for the increase in HOMA-IR in non-diabetic patients was
      investigated. RESULTS: Homeostasis model assessment of insulin resistance and IRI
      levels increased parallel with the progression of fibrosis. Among the non
      diabetic patients with mild to moderate liver fibrosis, BMI, serum levels of AST
      and TNF-alpha were related with HOMA-IR (BMI: r = 0.395, P = 0.041; AST: r =
      0.465, P = 0.014; TNF-alpha: r = 0.396, P = 0.040). In contrast, HOMA-IR related
      to TNF-alpha (r = 0.526, P = 0.013) in non-diabetic patients with advanced liver
      fibrosis. CONCLUSION: Collectively, hepatic fibrosis and inflammation appear to
      play key roles in the increase in insulin resistance in patients with chronic HCV
      infection.

PMID- 14675264
TI  - Evaluation of loss of heterozygosity before and after interferon therapy in
      patients with hepatitis C virus infection who developed hepatocellular carcinoma
      during follow up.
AB  - BACKGROUND AND AIM: The aim of the present study was to determine whether
      evaluating the status of loss of heterozygosity (LOH) before interferon (IFN)
      therapy is predictive for development of hepatocellular carcinoma (HCC) in
      chronic hepatitis and liver cirrhosis patients. METHODS: Eighteen patients with
      hepatitis C virus were studied, nine of whom developed HCC (HCC group) after IFN
      therapy and nine whom did not (non-HCC group). Samples before IFN therapy from
      both groups (pre-IFN-N and pre-IFN-H samples from the non-HCC and HCC groups,
      respectively) were analyzed for LOH using 12 microsatellite markers. To evaluate
      the LOH incidence in different steps in HCC patients, paired samples of cancerous
      tissue (CT) and adjacent non-CT (ANCT) obtained from the HCC group were also
      analyzed. RESULTS: Frequency of LOH in the pre-IFN-H samples was significantly
      higher than that in the pre-IFN-N samples regardless of the response to IFN
      therapy. Interestingly, in the HCC group, there is no significant difference in
      the frequency of LOH among the pre-IFN-H, ANCT and CT samples. CONCLUSIONS: The
      present results suggest the theory that genetic instability, such as LOH, had
      already accumulated at stages before the development of HCC. The authors propose
      that the status of LOH in chronic hepatitis and liver cirrhosis patients before
      IFN therapy could be a potential predictor for the development of HCC.

PMID- 14675265
TI  - Geographical difference in antimicrobial resistance pattern of Helicobacter
      pylori clinical isolates from Indian patients: Multicentric study.
AB  - AIM: To assess the pattern of antimicrobial resistance of Helicobacter pylori
      isolates from peptic ulcer disease patients of Chandigarh, Delhi, Lucknow,
      Hyderabad and Chennai in India, and to recommend an updated anti-H. pylori
      treatment regimen to be used in these areas. METHODS: Two hundred and fifty-nine
      H. pylori isolates from patients with peptic ulcer disease reporting for clinical
      management to the Post Graduate Institute of Medical Education and Research,
      Chandigarh; All India Institute of Medical Sciences, New Delhi; Sanjay Gandhi
      Post Graduate Institute of Medical Sciences, Lucknow; Deccan College of Medical
      Sciences and Allied Hospitals, Hyderabad; and hospitals in Chennai in
      collaboration with the Dr ALM Post Graduate Institute of Basic Medical Sciences
      were analyzed for their levels of antibiotic susceptibility to metronidazole,
      clarithromycin, amoxycillin, ciprofloxacin and tetracycline. The Epsilometer test
      (E-test), a quantitative disc diffusion antibiotic susceptibility testing method,
      was adopted in all the centers. The pattern of single and multiple resistance at
      the respective centers and at the national level were analyzed. RESULTS: Overall
      H. pylori resistance rate was 77.9% to metronidazole, 44.7% to clarithromycin and
      32.8% to amoxycillin. Multiple resistance was seen in 112/259 isolates (43.2%)
      and these were two/three and four drug resistance pattern to metronidazole,
      clarithromycin, amoxycillin observed (13.2, 32 and 2.56%, respectively).
      Metronidazole resistance was high in Lucknow, Chennai and Hyderabad (68, 88.2 and
      100%, respectively) and moderate in Delhi (37.5%) and Chandigarh (38.2%).
      Ciprofloxacin and tetracycline resistance was the least, ranging from 1.0 to 4%.
      CONCLUSION: In the Indian population, the prevalence of resistance of H. pylori
      is very high to metronidazole, moderate to clarithromycin and amoxycillin and low
      to ciprofloxacin and tetracycline. The rate of resistance was higher in southern
      India than in northern India. The E-test emerges as a reliable quantitative
      antibiotic susceptibility test. A change in antibiotic policy to provide scope
      for rotation of antibiotics in the treatment of H. pylori in India is a public
      health emergency.

PMID- 14675266
TI  - Appropriate cut-off value of 13C-urea breath test after eradication of
      Helicobacter pylori infection in Japan.
AB  - BACKGROUND AND AIM: A cut-off value of 2.5 per thousand for the 13C-urea breath
      test (UBT) is recommended in Japanese persons, based on the result of a
      multicenter trial in patients prior to treatment for eradication of Helicobacter
      pylori. The cut-off value of 2.5 per thousand has also been used in the
      assessment of eradication after treatment. The 6-8-week evaluation after
      treatment is recommended in the guidelines of the Japanese Society of
      Gastroenterology. The present study aimed to prospectively re-assess the cut-off
      value of the 13C-UBT at 6 weeks after treatment by using the results obtained at
      6 months as an indication of true positive or true negative H. pylori infection
      status. METHODS: One hundred and ninety patients who were positive for H. pylori
      underwent eradication treatment, and 177 patients of these patients who were
      assessed as having true positive or true negative H. pylori status at 6 months
      after treatment were evaluated in this study. Eradication was assessed by 13C
      UBT, culture, and histology at 6 weeks and at 6 months after treatment, and the
      cut-off value of 13C-UBT at 6 weeks was re-assessed. RESULTS: A cut-off value of
      3.5 per thousand. at 6 weeks after treatment showed 97.2% diagnostic accuracy,
      while a cut-off value of 2.5 per thousand at 6 weeks showed 96.0% diagnostic
      accuracy. For a 3.5 per thousand cut-off value, only five patients were positive
      by 13C-UBT and were negative by culture and histology at 6 weeks, and three
      patients were true positive and two were false positive by the 13C-UBT at 6
      months. CONCLUSION: A cut-off value of 3.5 per thousand for the 13C-UBT is
      recommended at 6 weeks after eradication treatment in Japanese persons.

PMID- 14675267
TI  - Helicobacter pylori-induced enlarged-fold gastritis is associated with increased
      mutagenicity of gastric juice, increased oxidative DNA damage, and an increased
      risk of gastric carcinoma.
AB  - BACKGROUND AND AIM: The severe inflammation, increased cell proliferation and
      marked acid inhibition observed in subjects with Helicobacter pylori-associated
      enlarged-fold gastritis suggest that enlarged-fold gastritis may be a risk factor
      for gastric carcinoma. The purpose of the present study was to determine whether
      a relationship exists between enlarged-fold gastritis and gastric carcinoma.
      METHODS: One hundred and thirty-five H. pylori-positive patients with early
      gastric carcinoma and 141 age- and sex-matched H. pylori-positive controls
      without gastric carcinoma were involved in the study. The widths of gastric body
      folds were measured by double-contrast radiographs. The mutagenicity of gastric
      juice was assayed using the Ames test and Salmonella typhimurium TA-98 or TA-100
      with S9-mix. Levels of 8-hydroxydeoxyguanosine (8-OHdG) in gastric mucosa were
      examined using high-performance liquid chromatographic-electrochemical detection.
      RESULTS: An upward shift in the distribution of gastric fold widths in H. pylori
      positive patients with early gastric carcinoma was found. Enlarged-fold gastritis
      (fold width >/=5 mm) was observed in 81% of the patients with gastric carcinoma,
      compared with 46% of H. pylori-positive controls. The odds ratio for gastric
      carcinoma increased with increasing fold width to a maximum of 35.5 in persons
      with fold width >/=7 mm. The prevalence of diffuse-type early gastric carcinoma
      in the body region increased with increasing fold width. The mutagenicity of
      gastric juice from the patients with enlarged-fold gastritis was significantly
      higher than that in H. pylori-negative controls and H. pylori-positive patients
      without enlarged folds. Mucosal 8-OHdG levels in the body region of patients with
      enlarged-fold gastritis were significantly higher than in H. pylori-negative
      controls and H. pylori-positive patients without enlarged-fold gastritis.
      Eradication of H. pylori significantly decreased the mutagenicity of gastric
      juice and 8-OHdG levels in the gastric mucosa from patients with enlarged-fold
      gastritis. CONCLUSION: A significant association is suggested between enlarged
      fold gastritis and gastric carcinoma.

PMID- 14675268
TI  - Symptom relief in patients with reflux esophagitis: comparative study of
      omeprazole, lansoprazole, and rabeprazole.
AB  - BACKGROUND AND AIM: Rabeprazole has a faster onset of antisecretory activity than
      omeprazole and lansoprazole. The aim of the present study was to clarify whether
      there is any difference in the speed of symptom relief in patients with reflux
      esophagitis following the administration of these three proton pump inhibitors
      (PPI). METHODS: Eighty-five patients with erosive reflux esophagitis were
      randomized to receive 8 weeks of 20 mg of omeprazole (n = 30), 30 mg of
      lansoprazole (n = 25), or 20 mg of rabeprazole (n = 30) once a morning. Daily
      changes in heartburn and acid reflux symptoms in the first 7 days of
      administration were assessed using a six-point scale (0: none, 1: mild, 2: mild
      moderate, 3: moderate, 4: moderate-severe, 5: severe). RESULTS: The mean
      heartburn score in patients administered rabeprazole decreased more rapidly than
      those given the other PPI. Complete heartburn remission also occurred more
      rapidly in patients administered rabeprazole (compared with omeprazole: P =
      0.035, compared with lansoprazole: P = 0.038 by log-rank test). No differences
      were seen in the rate of endoscopic healing of reflux esophagitis at 8 weeks
      between the three treatment regimens. CONCLUSION: Rabeprazole may be more
      effective than omeprazole and lansoprazole for the rapid relief of heartburn
      symptoms in patients with reflux esophagitis.

PMID- 14675269
TI  - Stomach myoelectrical response of patients with gastroesophageal reflux disease
      receiving omeprazole treatment.
AB  - BACKGROUND AND AIM: Proton pump inhibitor treatment is effective for
      gastroesophageal reflux disease (GERD). It is unknown whether these agents effect
      any change in the stomach myoelectricity of GERD patients. Electrogastrographic
      (EGG) recording was used to study the probable effect of omeprazole on GERD
      patients. METHODS: Nineteen endoscopically confirmed GERD patients and 38
      dyspepsia-free controls were invited to receive EGG recording. After daily
      omeprazole treatment for 4 weeks, the symptomatic response of GERD patients was
      scaled, healing of erosive esophagitis was endoscopically assessed, and EGG
      recording was repeated for comparison. RESULTS: Before treatment, GERD patients
      and controls displayed similar dominant frequency, whereas the former had higher
      dominant power compared with controls, either in fasting (29.2 +/- 6.0 dB
      compared with 25.3 +/- 3.8 dB, P < 0.01) or postprandial (31.9 +/- 5.6 dB
      compared with 27.7 +/- 3.8 dB, P < 0.001) recording. They also had diminished
      percentile normal rhythm (2-4 c.p.m.), irrespective of fasting (40.2 +/- 14.5%
      compared with 65.8% +/- 23.5%, P < 0.001) or postprandial (47.5 +/- 23.3%
      compared with 77.9 +/- 16.8%, P < 0.001) recording. After omeprazole treatment,
      healing was achieved in 12 patients (63.2%). Among the abnormal EGG parameters,
      only the postprandial percentile normal rhythm was restored (47.5 +/- 23.3%
      compared with 65.2 +/- 20.8%, P < 0.01). CONCLUSIONS: Gastroesophageal reflux
      disease patients may have obvious dysrhythmia and higher myoelectrical power.
      Effective omeprazole treatment only improves the postprandial myoelectrical
      regularity, whereas abnormal EGG parameters remain impaired.

PMID- 14675270
TI  - Herpes simplex esophagitis from 1307 autopsy cases.
AB  - BACKGROUND AND AIMS: The aim of the present study was to clarify relationship
      between macroscopic and microscopic features of herpes simplex esophagitis (HSE),
      and localization of herpes simplex virus type 1 (HSV-1)-infected cells in
      esophageal lesions from autopsy cases of histopathologically proven HSE. METHODS:
      The study comprised morphological, immunohistochemical, cultural and electron
      microscopic investigations for 24 HSE patients collected from 1307 serial autopsy
      cases in the past 10 years. RESULTS: Macroscopic characteristics of HSE were
      divided into three types. Types I and II showed small punched-out lesions with
      and without raised margins, respectively. Type III revealed that multiple ulcers
      became confluent like a map. Microscopic findings showed that the HSV infection
      process seemed to begin in squamous epithelium and to induce vertical cellular
      change into the intact epithelial layer. Intranuclear inclusion bodies were
      observed at the centers of lesions, and ballooning changes of squamous cells at
      the margins. Both localization of HSV-1-infected cells and presence of HSV-1 in
      the esophageal lesions were confirmed with immunohistochemical staining, viral
      culture and electron microscopy. CONCLUSION: The present results suggest that the
      macroscopic and microscopic postmortem features of HSE may provide useful
      information for clinical diagnosis of HSE.

PMID- 14675271
TI  - Prevalence of irritable bowel syndrome in young adult Malaysians: a survey among
      medical students.
AB  - BACKGROUND AND AIMS: Irritable bowel syndrome (IBS) is a common functional bowel
      disease in the West. Information on the prevalence of IBS in the Asian population
      is relatively scanty. The aims of the present study were to determine the
      prevalence of IBS and to assess the symptom subgroups based on the predominant
      bowel habit in a young adult population of Asian origin. METHODS: Basic
      demographic data and symptoms of IBS using the Rome I criteria were sought using
      a questionnaire administered to all apparently healthy students in a medical
      school. Other questions asked related to alcohol intake, smoking, chili
      consumption, dietary fiber intake, and to psychological and psychosomatic
      symptoms of anxiety, depression, insomnia, headache, and backache. The health
      care seeking behavior of the subjects was also analyzed. RESULTS: Of the 610
      questionnaires administered, 533 complete responses were received (response rate
      of 87.4%). The responders comprised 229 men (43.0%) and 304 (57.0%) women with a
      mean age of 22 +/- 1.8 years. The ethnic distribution was Malays 278 (52.2%),
      Chinese 179 (33.6%), Indians 46 (8.6%), and others 30 (5.6%). Eighty-four (15.8%)
      reported symptoms consistent with the diagnosis of IBS, predominantly women.
      Sixty-five (77.4%) and six (7.1%) were of the constipation-predominant and
      diarrhea-predominant IBS subgroups, respectively. Thirteen (15.5%) subjects fell
      into the non-specific IBS subgroup. The self-reported psychological and
      psychosomatic symptoms of anxiety (P = 0.02), depression (P = 0.002), insomnia (P
      = 0.006), headache (P = 0.04), and backache (P = 0.006) were encountered more
      frequently in the subjects with IBS. Only 13.1% of the IBS group had consulted
      their health-care practitioner, and 20.2% reported self-medication. CONCLUSIONS:
      Symptoms supportive of the diagnosis of IBS were common among young Malaysians,
      with a prevalence rate of 15.8%. There were significantly more women with IBS
      than men. Within the IBS population, the majority (77.4%) was of the constipation
      predominant IBS subgroup. A significantly higher prevalence of psychological and
      psychosomatic symptoms was found in individuals with IBS. Only a minority sought
      medical advice for their symptoms.

PMID- 14675272
TI  - Revalidation of description of constipation in terms of recall bias and visual
      scale analog questionnaire.
AB  - BACKGROUND AND AIM: The present study was designed to identify a cut-off value to
      define subjective and relatively objective criteria of constipation using the
      visual scale analog questionnaire (VSAQ) in healthy subjects. In addition, the
      importance of recall bias when evaluating constipation was investigated by
      repeating the questionnaire and ensuring the subjects maintained diaries.
      METHODS: Seven hundred and sixty healthy hospital personnel were questioned by
      means of a standard questionnaire. Subjects were initially asked if they were
      constipated (self-reported) and their daily defecation frequencies. Severity of
      the parameters of constipation, the consistency of defecation in the form of hard
      stools, straining and incomplete evacuation were also investigated using a VSAQ
      (0-10). Subjects were asked to complete a standard form about their daily bowel
      habits in the subsequent 7 days (diary). At the end of this series, the
      questionnaire forms completed at the beginning were readministered. Using the
      criteria of functional constipation, the prevalence of self-reported, symptom
      based (>/=2 criteria) and diary-based (>/=2 criteria in the diary) were defined.
      RESULTS: Of the subjects, 48.5% (369/760) completed diaries regarding their bowel
      habits and completed the questionnaire for the second time (198 female, 171 male;
      mean age 31.6 +/- 7.1 years). According to only interrogation, 29.8% of subjects
      reported that they were constipated; however, this number increased to 39.6% when
      symptom-based constipation (>/=2 criteria) was considered. Significant agreement
      was observed between the results of self-reported constipation in form I and II,
      and symptom-based and diary-based constipation (concordance = 77.7-98.6%, k =
      0.47-0.97). Furthermore, 98.1% of the subjects who reported that they were not
      constipated scored 3 on the VSAQ; conversely, 91.8% who accepted being
      constipated scored >3 for the same question. A total of 76.1% subjects who had
      symptom-based constipation scored 3 on the VSAQ, 97.3% of those who had <2
      criteria scored 3. When asked 'Are you constipated?' 1.2% of subjects with none
      of the criteria for diary-based constipation, and 10.7% of subjects who had one
      criteria scored >3 on the VSAQ. Also, 91.8% of those with three criteria and 100%
      of those with four criteria had a score >3 on the VSAQ for the same question.
      CONCLUSIONS: The prevalence of constipation in the questionnaire form based on
      self-reported, symptom-based and diary-based criteria were highly compatible with
      the result obtained on readministration. Recall bias was negligibly low. Also,
      the present results suggest that the diagnosis of constipation is more accurate
      when >2 criteria are present. In addition, the VSAQ seems to be sensitive enough
      to differentiate subjects with constipation from those without, when a score of 3
      has been chosen as the cut-off value for discrimination. However, this
      sensitivity was less in the group who stated they were constipated.

PMID- 14675273
TI  - Hepatobiliary and pancreatic: fatty liver, spared areas and aberrant gastric
      venous drainage.

PMID- 14675274
TI  - Gastrointestinal: duodenal Crohn's disease.

PMID- 14675275
TI  - Liver cirrhosis developed after ketoconazole-induced acute hepatic injury.
AB  - We describe a previously healthy woman who developed liver cirrhosis as a sequela
      of acute hepatic injury that was induced by ketoconazole administration to treat
      onychomycosis. The initial presentation of the disease was of a typical acute
      hepatitis, characterized by nausea, anorexia, fatigue, and jaundice that
      developed during the administration of ketoconazole. Many other causes of
      hepatitis were absent in the patient. Even though the hepatic injury was
      gradually resolved for several months after cessation of the drug, the liver
      function was not completely restored. Six months after the onset of illness, a
      follow-up abdominal computed tomography and peritoneoscopic liver biopsy were
      performed. They revealed a marked reduction in the liver volume and a definite
      cirrhotic change, which persisted for more than 5 years. The case suggests that
      the administration of ketoconazole can cause liver cirrhosis through acute
      hepatic injury within a short time under certain circumstances.

PMID- 14675278
TI  - Cadherin expression pattern in melanocytic tumors more likely depends on the
      melanocyte environment than on tumor cell progression.
AB  - BACKGROUND: Adhesion molecules have been assigned an important role in
      melanocytic tumor progression. By the loss of E-cadherin, melanocytes might
      escape the control of neighbouring keratinocytes. Although in vitro data support
      this hypothesis, there are yet no conclusive immunohistochemical results on
      cadherin expression in melanocytic tumors. OBJECTIVE: To gain detailed insight in
      the expression of cadherins and their cytoplasmic binding partners, the catenins,
      in various types of benign and malignant melanocytic neoplasms. METHODS:
      Immunohistochemical analysis of the expression of E-, P-, and N-cadherin and
      alpha-, beta-, and gamma-catenin in compound and dermal nevi, Spitz nevi, blue
      nevi, ultraviolet B (UVB)-irradiated nevi, and malignant melanomas of various
      tumor thickness. RESULTS: In both nevi and melanomas, E-cadherin expression in
      melanocytic cells decreased, following a gradient from junctional to deeper
      dermal localization. The pattern of E-cadherin expression was more heterogeneous
      in melanomas than in nevi. In some melanomas, E-cadherin was only weakly positive
      in the epidermal tumor cells. P-cadherin expression was similar to that of E
      cadherin. N-cadherin expression in melanocytic lesions was a rare finding,
      however, a small percentage of melanomas showed expression in some cell nests.
      Some Spitz nevi exhibited strong N-cadherin immunoreactivity. Most melanocytic
      cells were alpha- and beta-catenin-positive and gamma-catenin-negative. UVB
      irradiation did not influence the expression of cadherins and catenins in
      melanocytic nevi in vivo. CONCLUSIONS: It is presumed that the gradual loss of E
      cadherin expression represents a reaction of melanocytic cells to altered
      conditions in the dermal environment, e.g. lack of contact to keratinocytes, or
      new contact with dermal extracellular matrix molecules, respectively. Melanoma
      cells apparently are less dependent on these environmental factors and,
      therefore, show a more heterogeneous expression pattern. This might be of
      importance for the adaptation of the tumor cells to local requirements. However,
      in view of our results, a causative role of (loss of ) E-cadherin or (gain of ) N
      cadherin for melanocytic tumor progression still remains to be proven.

PMID- 14675279
TI  - Ets-1 immunohistochemical expression in non-melanoma skin carcinoma.
AB  - BACKGROUND: Ets-1 oncoprotein is a transcription factor known to regulate the
      expression of numerous genes important in extracellular matrix remodeling and
      angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety
      of human malignancies and to correlate with prognosis. To our knowledge, this
      oncoprotein has not been examined in non-melanoma skin carcinomas. DESIGN: A
      series of 26 primary cutaneous skin lesions with patient records were
      independently examined for diagnosis confirmation and immunohistochemical
      expression by two dermatopathologists. The immunohistochemical expression for Ets
      1 (Novocastra, Newcastle Upon Tyne, England, UK) was scored by an average of the
      mean labeling intensity (MLI), where no nuclear staining = 0, weak nuclear
      staining = 1, moderate nuclear staining = 2, and strong nuclear staining = 3.
      RESULTS: All basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC) cases
      exhibited negative nuclear staining, for an average MLI of 0. Keratoacanthomas,
      squamous cell carcinoma in situ (SIS), and well-differentiated squamous cell
      carcinomas (SCCs) exhibited negative to weak nuclear staining, for an average MLI
      of 0.4 +/- 0.3. Moderately differentiated SCCs exhibited moderate nuclear
      staining, for an average MLI of 1.8 +/- 0.6. Poorly differentiated SCCs and
      metastatic SCCs exhibited very strong nuclear staining, with an average MLI of
      2.8 +/- 0.2. CONCLUSIONS: Ets-1 is not expressed in cutaneous BCC or MCC and is
      weakly expressed in SIS and forms of well-differentiated SCC. Although the
      intensity of Ets-1 immunostaining distinguished between well-differentiated and
      poorly differentiated SCC (p < 0.0001), it failed to discriminate between in situ
      and well-differentiated SCCs. The preliminary data suggests Ets-1 may be
      important in the pathogenesis of invasive SCC.

PMID- 14675280
TI  - Antigen distribution and antigen-presenting cells in skin biopsies of human
      chromoblastomycosis.
AB  - BACKGROUND: Chromoblastomycosis is a chronic, suppurative, granulomatous mycosis
      usually confined to skin and subcutaneous tissues. The host defense mechanisms in
      chromoblastomycosis have not been extensively investigated. The purpose of the
      present study was to determine the distribution and pathways of the fungal
      antigen(s) and the possible role of the different immunocompetent cells in
      antigen processing in skin lesions. METHODS: The distribution of Fonsecaea
      pedrosoi antigen(s) in human skin was studied in 18 biopsies from 14 patients
      with chromoblastomycosis. A purified polyclonal immune serum raised in rabbits
      against metabolic antigen(s) of F. pedrosoi was used to detect yeast antigen(s)
      by immunohistochemical procedures. Double immunolabeling was performed with yeast
      antigen(s) and Langerhans' cells [labeled with anti-S100 protein monoclonal
      antibody (MoAb)], yeast antigen(s) and factor XIIIa+ dermal dendrocytes
      (immunolabeled with anti-factor XIIIa polyclonal antibody), and yeast antigen(s)
      and macrophages (labeled with CD 68 monoclonal antibody). RESULTS: The F.
      pedrosoi antigen(s) accumulated in the skin macrophages and, in a few instances,
      in factor XIIIa+ dendrocytes and Langerhans' cells. CONCLUSIONS: The data
      obtained suggest that chiefly macrophages, also Langerhans' cells and factor
      XIIIa+ dermal dendrocytes, function as antigen-presenting cells in
      chromoblastomycosis.

PMID- 14675281
TI  - Follicular squamous cell carcinoma of the skin: a poorly recognized neoplasm
      arising from the wall of hair follicles.
AB  - BACKGROUND: In the last decades, a number of clinicopathologic subtypes of
      squamous cell carcinoma (SCC) of the skin, ranging from highly aggressive tumors
      with a tendency to recur and metastasize to neoplasms with a favorable prognosis,
      have been described. SCCs arising from the wall of hair follicles have been
      briefly mentioned by some authors but never reported in a series. METHODS: Cases
      of SCC arising from the wall of hair follicles were collected from the files of
      two large German Centers for Dermatopathology and analyzed clinicopathologically
      and immunohistochemically. RESULTS: Sixteen cases of SCC developing in hair
      follicles were found among more than 7000 cases of cutaneous SCC reviewed. In
      most cases, tumors arose on sun-damaged skin of the face of elderly persons.
      There was a male predominance (11/5). The most common clinical diagnosis was
      basal cell carcinoma (BCC). Microscopically, tumors developed in the upper part
      of hair follicles without or with focal involvement of the overlying epidermis at
      the border with the involved follicle. Immunohistochemically, tumors were
      positive for cytokeratin and negative for a battery of immunomarkers, including
      antibodies against the most common carcinogenic human papillomaviruses (HPV) of
      the skin. Most tumors were excised by simple excision. In two cases, a recurrence
      was noted after incomplete excision. No further recurrences or metastasis have
      been noted after a follow-up period ranging from 11 months to 12 years.
      CONCLUSION: SCC of the hair follicle represents a poorly recognized but
      distinctive subset of SCC of the skin that should be considered in the
      differential diagnosis of other cutaneous epithelial tumors. The term follicular
      SCC (FSCC) is proposed for this neoplasm.

PMID- 14675282
TI  - Histological characterization of regression in acquired immunodeficiency syndrome
      related Kaposi's sarcoma.
AB  - BACKGROUND: Kaposi's sarcoma (KS) is an angioproliferative lesion that may
      regress or progress. Progression is related to spindle cell proliferation and the
      expression of human herpes virus-8 latency genes, including latent nuclear
      antigen-1 (LNA-1), cyclin-D1, and bcl-2. KS regression has not been well
      characterized histologically. Therefore, this study was undertaken to
      characterize the histopathology of pharmacologically induced regressed cutaneous
      KS. METHODS: Skin punch biopsies from eight patients with acquired
      immunodeficiency syndrome (AIDS)-related KS, that regressed following
      chemotherapy with paclitaxel or the angiogenesis inhibitor Col-3, were
      investigated by light microscopy. Comparative immunophenotyping on pre- and post
      treatment specimens for CD31, LNA-1, cyclin-D1, bcl-2, and CD117 (c-kit) was
      performed. RESULTS: Clinical and histologic features of regression were similar
      for paclitaxel and Col-3 treatment. On clinical examination, lesions flattened,
      became smaller, and lost their purple-red appearance, resulting in an orange
      brown macule. Histological regression was divided into partial (n = 3) and
      complete (n = 5) regression. Partially regressed lesions had a significant
      reduction of spindle cells in the dermal interstitium, with residual spindle
      cells arranged around superficial and mid-dermal capillaries. Complete regression
      was characterized by an absence of detectable spindle cells, with a slight
      increase in capillaries of the superficial plexus. All regressed samples
      exhibited a prominent, superficial, perivascular, lymphocytic infiltrate and
      abundant dermal hemosiderin-laden macrophages. This clinicopathologic picture
      resembled the findings of pigmented purpura. CD31 staining correlated with the
      reduction of spindle cells. Regression was accompanied by a quantitative and
      qualitative decrease in LNA-1 and cyclin-D1 immunoreactivity, but no change in
      bcl-2 or c-kit expression. CONCLUSIONS: Pharmacologically induced regression of
      AIDS-related cutaneous KS is characterized by a complete loss or decrease of
      spindle cells, increased lymphocytes, and prominent dermal siderophage
      deposition. Without any prior knowledge of the history of KS regression following
      therapy, regressed KS lesions may be misdiagnosed clinically and histologically
      as pigmented purpuric dermatitis.

PMID- 14675283
TI  - Possible role of Malassezia furfur in psoriasis: modulation of TGF-beta1,
      integrin, and HSP70 expression in human keratinocytes and in the skin of
      psoriasis-affected patients.
AB  - BACKGROUND: Psoriasis is a disease characterized by an abnormal pattern of
      keratinocyte growth and differentiation. Malassezia furfur forms part of the
      normal human skin flora. It may also be involved in the pathogenesis of
      psoriasis. To define the role of M. furfur in the pathogenesis of psoriasis, we
      investigated how M. furfur regulates molecules involved in cell migration and
      proliferation. The experiments were performed using human keratinocytes and skin
      biopsies from M. furfur-positive and -negative psoriasis-affected patients. In
      addition, we examined the signal transduction mechanisms involved. MATERIALS AND
      METHODS: Western blot analysis was performed on human keratinocytes lysates
      treated or untreated with M. furfur and on biopsies from healthy and psoriasis
      patients. Signal transduction mechanisms involved were evaluated by
      electrophoretic mobility shift assay using the AP-1 inhibitor curcumin. RESULTS:
      We found that M. furfur up-regulates transforming growth factor-beta1 (TGF
      beta1), integrin chain, and HSP70 expression in human keratinocytes via AP-1
      dependent mechanism. In the biopsies of M. furfur-positive psoriasis-affected
      patients, an increase in TGF-beta1, integrin chains, and HSP70 expression was
      found. CONCLUSION: Our data suggest that M. furfur can induce the overproduction
      of molecules involved in cell migration and hyperproliferation, thereby favoring
      the exacerbation of psoriasis.

PMID- 14675284
TI  - Parvoviral infection of endothelial cells and stromal fibroblasts: a possible
      pathogenetic role in scleroderma.
AB  - BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease (CTD) which
      differs from other CTDs by progressive irreversible fibrosis in lung, kidney,
      skin, and heart. It has a worse prognosis compared to several other CTDs. The
      pathogenesis may reflect a humorally mediated microangiopathy in concert with the
      overproduction of collagen triggered by immune-mediated cytokine production.
      Having previously demonstrated parvovirus B19 (B19) DNA in bone marrow and skin
      biopsies of SSc patients in the absence of B19 viremia, we sought to further
      elucidate a role for B19 in the pathogenesis of SSc. DESIGN: Twelve patients who
      fulfilled American College of Rheumatology criteria for a diagnosis of SSc were
      encountered. Ten were serologically screened for B19 infection. Solution phase
      polymerase chain reaction (PCR) for B19 DNA was performed on skin tissue from six
      patients, and in all biopsies, reverse transcriptase in situ PCR (RT in situ PCR)
      for B19 and tumor necrosis factor (TNF)-alpha mRNA was performed. B19 viral
      protein (VP2) expression was sought by immunohistochemistry and correlated to PCR
      findings and to light microscopy of hematoxylin and eosin-stained sections.
      Frozen tissue was also available on five of the patients. Two control groups were
      assessed for B19 and TNF expression comprising one with irrelevant primers and
      the other representing 18 cases of inflammatory skin lesions where the etiology
      was known and unrelated to B19 infection. In addition, frozen and paraffin
      embedded tissues procured from skin lesions unrelated to B19 infection were
      assessed for B19 genome. In all cases, pretreatment with RNase was also performed
      to verify that any positive signal was indeed RNA based. RESULTS: Diffuse SSc was
      seen in seven patients, and limited disease in five. All patients had an
      antinuclear antibody--specifically, an antinucleolar, anticentromere, and/or anti
      Scl 70 antibody. Eleven of the 12 had lung involvement, whereas eight patients
      had myocardial disease. Of 12 patients tested serologically, nine had B19
      specific antibodies, which included immunoglobulin M (IgM)-specific antibodies in
      two cases. Solution phase PCR showed B19 DNA in the skin in three cases and in
      the bone marrow in three cases, including two in whom skin-based B19 DNA was
      observed. In all cases, RT in situ PCR demonstrated B19 and TNF-alpha mRNA in
      endothelia, fibroblasts, mast cells, and perivascular inflammatory cells.
      Immunohistochemistry to assess VP2 was either negative or equivocal.
      Immunofluorescent studies revealed prominent deposition of C5b-9 within the
      cutaneous vasculature from biopsies of all patients tested. The control samples
      were negative for B19 and TNF RNA and DNA. CONCLUSIONS: Parasitism of endothelia
      and fibroblasts by B19 with resultant enhanced TNF-alpha expression may be of
      pathogenetic importance in SSc even in the absence of demonstrable viremia. The
      vascular deposition of C5b-9 suggests a role for humoral immunity possibly
      induced by a state of endothelial neoantigenicity evoked by virally mediated cell
      injury. Treatment strategies include anti-viral therapy, including in the context
      of intravenous gamma-globulin and anti-TNF therapy.

PMID- 14675285
TI  - Immunohistochemical study of chronological and photo-induced aging skins using
      the antibody raised against D-aspartyl residue-containing peptide.
AB  - BACKGROUND: Biologically uncommon D-aspartyl residues have been reported in the
      elderly tissues such as tooth, eye lens, aorta, and brain. We have previously
      prepared the antibody against D-aspartyl residue-containing peptide and found
      that it reacted with elastotic material of actinic elastosis. METHODS:
      Immunoreactivity of the normal skins obtained from sun-exposed and sun-protected
      skins of varied ages with this antibody was studied. RESULTS: In the sun-exposed
      skins, the antibody showed negative reaction with the skin specimens of young
      donors, whereas it reacted with elastotic materials of actinic elastosis of the
      elderly. In the sun-protected skins, the antibody recognized elastic fiber-like
      structures and inner layer of vessels found from the mid to lower dermis of old
      donors but showed no positive reaction to skin specimens of young donors.
      CONCLUSIONS: The results suggest that the antibody is a potent marker for
      chronological and ultraviolet (UV)-induced skin aging. Unusual eosinophilic
      bodies seen in the superficial dermis in the sun-exposed area of the elderly
      skins were also immunoreactive with the antibody, suggesting that the
      eosinophilic bodies resulted from UV-induced skin damage.

PMID- 14675286
TI  - Procollagen 1 expression in atypical fibroxanthoma and other tumors.
AB  - BACKGROUND: Procollagen (PC) is secreted by fibroblasts into the extracellular
      matrix, where it is cleaved to form collagen. The rat anti-human PC-1 monoclonal
      antibody has been reported to react with atypical fibroxanthoma (AFX), a poorly
      differentiated but usually benign skin lesion common in elderly patients. We have
      studied PC-1 staining in 50 tumors with AFX histological features (four of which
      were subsequently reclassified as non-AFX tumors) to confirm this prior
      observation. In addition, we have investigated PC-1 in other skin tumors,
      particularly those with spindled cell or sclerosing/desmoplastic morphologies.
      METHOD: Archival material was retrieved and sections were prepared and
      immunostained with PC-1 as well as a panel of antibodies, including S-100 and MNF
      116 (cytokeratins 5, 6, 7, 8, 17, and 19). RESULTS: PC-1 staining was strongly
      positive in 40 of 46 (87%) AFXs. Three AFXs displayed weak staining with PC-1
      even after repeat staining of 10 tumors that were initially weak. Three
      additional tumors stained with both PC-1 and MNF-116 and were classified as AFX
      like squamous cell carcinoma (SCC). One tumor with AFX-like histology was PC-1
      negative and S-100 positive and was classified as an AFX-like melanoma. Positive
      staining in tumor cells was observed in three of nine (33%) desmoplastic
      malignant melanomas, three of eight (38%) desmoplastic SCCs, zero of 10 (0%)
      desmoplastic trichoepitheliomas, zero of 10 (0%) morpheic basal cell carcinomas,
      and zero of 10 (0%) sclerosing sweat duct carcinomas. CONCLUSION: PC-1 is a
      useful antibody in a diagnostic immunohistochemical panel when investigating AFX
      and AFX-like tumors; however, good technical quality and careful interpretation
      are necessary when using a panel of antibodies, particularly to keratin and S-100
      protein, for optimal accuracy.

PMID- 14675287
TI  - Dermatofibrosarcoma protuberans association with nuchal-type fibroma.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a hypercellular, storiform,
      CD34-positive low-grade sarcoma with honeycomb entrapment of fat, which typically
      involves the trunk and extremities. Nuchal-type fibroma (NTF ) is a
      paucicellular, CD34-positive fibrous tumor with fat entrapment, which may occur
      in both nuchal and extranuchal locations and in association with Gardner
      syndrome. METHODS: We report the association of DFSP with NTF in a 43-year-old
      male with no personal or family history of Gardner syndrome. RESULTS: The patient
      had a past history of a DFSP removed from his back, which recurred 2 years later
      and was re-excised. Additionally, the patient had a typical NTF, in the posterior
      neck, removed at the same time. Histopathologic examination of the recurrent back
      lesion demonstrated a composite lesion with typical appearances of DFSP,
      centrally, blending into an NTF-like appearance, peripherally. Both components
      expressed CD34 and CD99, and lacked elastin. A review of the microscopic slides
      of the patient's previously excised DFSP revealed an identical lesion with
      surrounding NTF-like areas. CONCLUSION: While an association between NTF and
      fibromatosis has recently been reported, this is to our knowledge the first
      report of an association between NTF and DFSP. The morphologic findings suggest
      that there may be a continuum between these two CD34-positive lesions that have a
      tendency to infiltrate adipose tissue and recur.

PMID- 14675288
TI  - Proximal-type epithelioid sarcoma: case report and result of comparative genomic
      hybridization.
AB  - BACKGROUND: Epithelioid sarcoma is a rare mesenchymal neoplasm. Recently, a more
      aggressive, so-called "proximal type" epithelioid sarcoma has been described.
      CLINICAL CASE: A 40-year-old-woman presented with 5 x 4 cm, erythematous,
      indurated, non-movable, painful mass on the pubic area. Histopathology
      demonstrated diffuse tumor-cell infiltration into the subcutaneous and fascia,
      which was consisted of prominent epithelioid cells and scattered rhabdoid cells.
      A multinodular growth pattern or granulomatous appearance with central necrosis
      was not observed. The tumor cells showed positive reactions for vimentin,
      cytokeratin (AE1/AE3), and CD34. Despite the surgery, left inguinal mass with
      lymphadenopathy occurred one month later. We also carried out comparative genomic
      hybridization (CGH) with tumor cells. CGH revealed chromosomal gain of 5q32-qter,
      12q24-qter, and 22q. CONCLUSION: We report a case of proximal-type of epithelioid
      sarcoma, which showed the chromosomal gains of 5q32-qter, 12q24-qter, and 22q by
      CGH.

PMID- 14675289
TI  - Mid-dermal elastolysis preceded by acute neutrophilic dermatosis.
AB  - BACKGROUND: Mid-dermal elastolysis is a rare idiopathic elastic tissue disorder
      that is characterized by localized patches of finely wrinkled skin and a "band
      like" loss of elastic tissue in the mid-reticular dermis. Lesions may be preceded
      by erythema and/or urticaria, and histological examination of inflamed lesional
      skin may demonstrate lymphohistiocytic dermal infiltration. CASE REPORT: We
      report a case of mid-dermal elastolysis in a 31-year-old woman who developed
      multiple erythematous and urticarial plaques on the arms and trunk. Histologic
      examination of a representative lesion revealed a neutrophilic infiltrate and a
      normal pattern of elastic tissue. Several months later, the erythema and
      urticaria was noted to have resolved, leaving soft, pendulous plaques with
      overlying finely wrinkled skin. A follow-up biopsy at this time showed minimal
      lymphocytic inflammation but almost complete absence of elastic tissue in the mid
      reticular dermis. CONCLUSIONS: To our knowledge, acute neutrophilic dermatosis
      resulting in mid-dermal elastolysis has not been previously described. This
      observation lends support to an emerging theory that the pathogenesis of mid
      dermal elastolysis may be inflammatory.

PMID- 14675290
TI  - Cutaneous lobular capillary hemangioma induced by pregnancy.
AB  - Lobular capillary hemangioma, which is also named as pyogenic granuloma, is a
      common vascular proliferation of skin and mucous membranes. Hormonal influence in
      the development of lobular capillary hemangioma on the mucosal surfaces has been
      demonstrated but for cutaneous lesions located on the skin, this association has
      not been shown yet. In this report, a 25-year-old female patient with cutaneous
      lobular capillary hemangioma of the cheek induced by pregnancy is presented. The
      lesion was excised and lobular capillary hemangioma was given as diagnosis by
      histopathological evaluation. Estrogen receptor was weakly positive by
      immunohistochemical analysis. We suggest that elevated levels of estrogens during
      pregnancy may have an important role also on the development of cutaneous lobular
      capillary hemangiomas by direct hormonal action.

PMID- 14675296
TI  - Primary nurses' performance: role of supportive management.
AB  - BACKGROUND: Most studies examining primary nursing focus on outcome variables
      such as enhanced patient and staff satisfaction with care, perceived autonomy and
      quality of care, whereas only limited research has examined processes of
      implementing and maintaining primary nursing. In addition, the few studies that
      have explored process variables discuss only direct relationships between the
      design of the primary nursing care-delivery system, process and nurse outcomes,
      and disregard how such variables interact. AIM: This study sought to address
      previous inconsistent findings about the impact of primary nursing care-delivery
      models on the performance of nurses by incorporating the moderating role of
      supportive management practices. METHOD: Three hundred and sixty-eight nurses
      from a variety of wards completed questionnaires that assessed the degree of
      primary nursing on their unit, the support practices of their direct supervisor
      and their perceptions of the cost of seeking support from their supervisor. In
      addition, the direct supervisor evaluated the nurse's performance in the unit.
      RESULTS: Primary nursing did not exert a direct impact on nurses' performance.
      Rather, the interaction of primary nursing with supervisor support was more
      predictive of performance: if supervisor support was high, performance was
      substantially higher than if supervisor support was low. In addition, nurses'
      perceptions of the costs of seeking support had a detrimental impact on their
      performance. CONCLUSIONS AND LIMITATIONS: The study was cross-sectional and
      relied on self-report data only. Nevertheless, the findings show that supportive
      management practices are crucial to the success of implementing primary nursing.

PMID- 14675297
TI  - Health visiting: the public health role.
AB  - BACKGROUND: United Kingdom (UK) government policy advocates the development of a
      family-centred public health role for health visitors. Studies have suggested
      that barriers and constraints exist to hinder the development of a public health
      role. However, few of these have considered the issues from a practitioner
      perspective. AIM: The aim of the study was to examine the constraints on
      developing a family-centred public health role in a health visiting service.
      METHODS: An exploratory study was carried out using focus groups with 27 health
      visitors in one primary health care trust in North West England. Data were
      transcribed and analysed to identify themes. FINDINGS: Elements of practice that
      contributed to public health were identified, along with constraints on the
      development of a family-centred public health role. Three themes were generated
      from the health visitor focus group discussions as a framework for addressing the
      constraints: connecting to public health, clarifying the role and changing
      practice. CONCLUSIONS: The study sets out the challenge faced in developing the
      public health roles of practitioners. Leadership is essential for clarifying the
      public health role, developing networks between public health and practitioners,
      and supporting change in practice. Despite the limitations of the study, its
      findings, together with evidence from previous literature, suggest that there are
      common issues that face health visiting services in the UK as they seek to
      develop the public health role.

PMID- 14675298
TI  - Paternal postpartum depression, its relationship to maternal postpartum
      depression, and implications for family health.
AB  - BACKGROUND: Much attention has been paid to the problem of postpartum depression
      in women. However, there is some indication that men also experience depression
      after the birth of a child, and that paternal depression is linked to maternal
      depression. AIMS: The purpose of this integrative review was to examine current
      knowledge about postpartum depression in fathers. Specific aims were (1) to
      examine the incidence of paternal depression in the first year after the birth of
      a child, (2) to identify the characteristics and predictors of paternal
      postpartum depression, (3) to describe the relationship between maternal and
      paternal postpartum depression, and (4) to discuss the influence of paternal
      depression on the family and infant. METHODS: A literature search from 1980 to
      2002 was carried out using the CINAHL, PsychInfo, and Medline electronic
      databases. Twenty research studies were identified that included incidence rates
      of paternal depression during the first year postpartum. These were further
      examined and synthesized regarding onset, severity, duration, and predictors of
      paternal depressive symptoms, and for information about the relationship between
      maternal and paternal depression. FINDINGS: During the first postpartum year, the
      incidence of paternal depression ranged from 1.2% to 25.5% in community samples,
      and from 24% to 50% among men whose partners were experiencing postpartum
      depression. Maternal depression was identified as the strongest predictor of
      paternal depression during the postpartum period. The implications of parental
      depression for family health were discussed. CONCLUSIONS: Postpartum depression
      in men is a significant problem. The strong correlation of paternal postpartum
      depression with maternal postpartum depression has important implications for
      family health and well-being. Consideration of postpartum depression in fathers
      as well as mothers, and consideration of co-occurrence of depression in couples,
      is an important next step in research and practice involving childbearing
      families.

PMID- 14675299
TI  - Technology-dependent children and their families: a review.
AB  - BACKGROUND: Advances in medical technology and nursing care have enabled children
      who rely on long-term medical and technical support to reunite with their
      families and community. The impact of discharging these children into the
      community involves a number of unprecedented social implications that warrant
      policy consideration. To begin with, an effort must be made to understand the
      phenomenon of caring for technology-dependent children living at home. AIM: The
      aim of this paper is to provide a comprehensive literature review on caring for
      technology-dependent children living at home. METHODS: The review was conducted
      via keyword searches using various electronic databases. These included CINAHL,
      MEDLINE, Social Science Index, Sociological Abstracts, Australian Family and
      Society Abstracts, and the Australian Bureau of Statistics. The articles and
      books found were examined for commonality and difference, significant themes were
      extracted, and the strength of the research methods and subsequent evidence were
      critiqued. FINDINGS: In this paper, themes relating to home care for technology
      dependent children and their families are elucidated and summarized. These are:
      chronic illness and children; the impact of paediatric home care on children; the
      uniqueness of technology-dependent children and their families; and parents'
      experience of paediatric home care. DISCUSSION: Contentious issues, relevant to
      the social life of these children and their families, are raised and are
      discussed with the intention of extending awareness and provoking further debate
      among key stakeholders. These issues include: the changed meaning of home; family
      dynamics; social isolation; saving costs for whom?; shifts in responsibility; and
      parent-professional relationships. CONCLUSION: More research is needed in the
      arena of paediatric home care, to facilitate relevant policy formation and
      implementation.

PMID- 14675300
TI  - Coping strategies of people with kidney transplants.
AB  - BACKGROUND: There has been little research into coping process following renal
      transplantation, but it has been shown that health-related stress is not
      eliminated and that fear of rejection and economic factors are the most stressful
      issues. Coping strategies used have included prayer, looking at problems
      objectively, and trying to main control over the situation. AIM: The study was
      concerned with kidney transplant patients and their efforts to cope with problems
      posed by the transplantation and treatment. The aim was to describe and compare
      the use and perceived effectiveness of different coping strategies in people
      after kidney transplant with an age, gender and civil status-matched sample of
      the general Swedish population. METHODS: Coping was assessed by the Jalowiec
      Coping Scale and self-rated efficiency with visual analogue scales. From a total
      of 73 post-transplant patients, a consecutive series of 30 was compared with an
      age, gender and civil status-individually matched sample of the general Swedish
      population (n = 30). Data were collected from 1994 to 1997. RESULTS: The patient
      sample used significantly more optimistic, self-reliant, supportive and emotive
      coping than the general population sample. Evasive, emotive, and fatalistic
      coping were associated with low perceived efficiency in handling various aspects
      of the condition. STUDY LIMITATIONS: The study design does not permit causal
      conclusions and the patient sample was relatively small and non-randomly chosen,
      which could affect its external validity. CONCLUSIONS: The results suggest that
      assessment of coping strategies should be explored in clinical nursing practice
      so that nurses can encourage the use of those likely to be more useful, and
      discourage those with possible negative effects.

PMID- 14675301
TI  - Decision-making in clinical nursing: investigating contributing factors.
AB  - BACKGROUND: This article describes the results of a study which investigated the
      contextual factors influencing clinical decision-making. Education and experience
      have been suggested by some as having a positive effect on clinical decision
      making, and have been listed as being of high importance. Values, knowledge,
      clinical setting and stress have also been identified as being important to
      decision-making, with various rankings given by different researchers. AIM: The
      study was undertaken to determine relationships between occupational orientation
      (value to role), educational level, experience, area of practice, level of
      appointment, age and clinical decision-making in Australian nurses. The
      predictive ability of each factor on clinical decision-making was determined.
      METHOD: This correlational study examined Australian nurses' decision-making
      about some common nursing interventions and 'occupational orientation',
      educational level, experience, level of appointment, area of clinical speciality
      and age. A model was constructed using stepwise selection regression to predict
      the 'weight' of each variable in clinical decision-making. RESULTS: Education and
      experience were not significantly related to decision-making. The factor that
      accounted for the greatest variability to clinical decision-making was holding a
      professional occupational orientation, followed by level of appointment, area of
      clinical speciality, and age in that order. CONCLUSION: In contrast to other
      studies, experience and educational level were not found to influence decision
      making strongly, the value of role was the most significant predictor. The model
      developed, however, only accounted for a low amount of variability in decision
      making. The findings indicate that there are other factors affecting clinical
      decision-making that still require identification.

PMID- 14675302
TI  - Autonomy and integrity: upholding older adult patients' dignity.
AB  - AIM: The aim of this study was to deepen understanding of the relationship
      between autonomy and integrity in interactions between patients and individual
      health care workers in real-life care situations. METHOD: The data reported here
      are from a 6- and 12-month follow-up of the teaching of ethics to health care
      professionals working with older people. The data collection method used was
      participant observation. Health professionals' caring behaviour in everyday
      situations was observed from the point of view of patients' autonomy and
      integrity. Theoretical frameworks relating to autonomy and integrity were used to
      analyse the data. FINDINGS: The structural framework was useful for identifying
      the two concepts and their relationship in everyday situations. The data suggest
      that the two concepts are ethically complex. Autonomy is grounded in respect for
      patients' ability to choose, decide and take responsibility for their own lives.
      Autonomy varies within and between individuals and is dependent on context and on
      those involved. It stresses the intrinsic value of patients, which marks their
      worth independently of others. Integrity, however, is bound to patients' very
      existence, no matter what their physical and mental conditions, and must be
      respected regardless of their ability to act autonomously. CONCLUSION: The
      concepts of autonomy and integrity appear to presuppose one another and to be
      indivisible if older adult patients' dignity is to be maintained. This implies
      that when patients' autonomy is supported their integrity is protected and,
      consequently, their dignity upheld.

PMID- 14675303
TI  - Quality of life of clients with schizophrenia.
AB  - BACKGROUND: Because of the deinstitutionalization of mental health care in Hong
      Kong that has taken place since the 1980s, many people with mental health
      problems are being cared for in the community. The majority of clients have a
      diagnosis of schizophrenia, and many have a long duration of illness and multiple
      readmissions. There is concern about their quality of life. AIM: To investigate
      quality of life and related factors in clients with a diagnosis of schizophrenia
      in Hong Kong. DESIGN: A convenience sample was recruited from a psychiatric
      outpatient department. Structured face-to-face interviews were conducted using
      the Brief Psychiatric Rating Scale and the Hong Kong Chinese World Health
      Organization Quality of Life Scale-Brief Version. RESULTS: A total of 172 people
      participated in the study. Most of them were single and unemployed. They were
      least satisfied with their psychological health, financial situation, life
      enjoyment and sexual activity. Women (n = 91) reported less satisfaction with
      quality of life than men (n = 86). Unemployed people (n = 100) were less
      satisfied with their quality of life than the employed (n = 76). Higher levels of
      mental health problems and higher numbers of previous hospitalizations were
      associated with negative perceptions of quality of life. DISCUSSION: People with
      mental health problems had significantly less satisfaction with their quality of
      life than a sample from the general population in Hong Kong surveyed in a
      previous study. As well as experiencing distressing mental symptoms, they had
      many difficulties, such as financial problems, unemployment and lack of
      opportunities to participate in social activities, that resulted from stigma and
      discrimination. These had a great impact on their quality of life. STUDY
      LIMITATIONS: Because of the small sample size and its convenience nature, the
      findings may not be generalizable to all clients in Hong Kong. A generic
      instrument was used to measure quality of life, and this may not have been
      sensitive to certain aspects of mental health clients' lives. CONCLUSION: The
      findings suggest that there is a need to strengthen social and vocational
      rehabilitation for people with mental health problems in Hong Kong. A more
      holistic and intensive model of care is required to meet their complex needs. A
      larger and more diverse sample should be used in future research, and a quality
      of life measure specifically designed for people with mental health problems
      should be used.

PMID- 14675304
TI  - Randomized controlled trials of socially complex nursing interventions: creating
      bias and unreliability?
AB  - BACKGROUND: The randomized controlled trial is viewed by many researchers as the
      'gold standard' research design. It is used increasingly to evaluate the
      effectiveness of socially complex activities such as nursing interventions. This
      use is seen by many commentators as problematic, while others are concerned about
      the quality of many published trial reports. One area of concern is that of
      intervention bias: the impact that a sentient intervention, such as a nursing
      one, may have consciously or unconsciously on study outcomes. This paper reports
      on an analysis of intervention definitions and possible intervention bias in 47
      reports of randomized controlled trials of nursing interventions published in
      2000 or 2001. AIMS: This study evaluates four characteristics of the included
      reports: intervention sample size, intervention definition, involvement of
      intervention nurses in other aspects of the trial, and the claimed
      generalizability of results. METHODS: Reports of randomized controlled trials
      published in 2000 or 2001 were identified. Full-text versions of 47 papers were
      obtained and information about the four characteristics was extracted and
      analysed. RESULTS: Problems relating to possible intervention bias were
      identified in each of the papers. Inadequate intervention definition was the
      commonest problem, leading to difficulties in calculating the 'intervention dose'
      and in replicating or generalizing from the studies. DISCUSSION: None of the
      included studies met the requirements of the Consolidated Standards of Reporting
      Trials. Four types of intervention bias were identified, and their possible
      implications for the reporting of trials of nursing interventions are discussed.
      This was a small-scale study, limited by time and resources. Its results are
      suggestive of a major problem of intervention bias but larger-scale
      investigations are necessary to quantify its extent. CONCLUSIONS: Intervention
      bias is potentially a problem in randomized controlled trials. Lack of detail
      about interventions in published papers could be corrected by stricter adherence
      to guidelines such as the Consolidated Standards of Reporting Trials, but this
      will not correct the underlying problem of inadequate study design that appears
      to be widespread in randomized controlled trials of nursing interventions.

PMID- 14675305
TI  - Revising the critical care family needs inventory for the emergency department.
AB  - BACKGROUND: The Critical Care Family Needs Inventory (CCFNI) has been used widely
      over the last two decades for analysing the needs of family members in the
      intensive care unit. However, it has significant limitations as a needs
      assessment tool for use with families in the Emergency Department (ED). This
      paper discusses the methodological challenges encountered during the process of
      reviewing and adapting this tool for use in the ED. AIMS: The purpose of this
      study was to revise and adapt the CCFNI for use with a population of family
      members of critically ill patients in an Australian Emergency Department.
      INSTRUMENT: The process of tool revision, adaptation and reconstruction included:
      critique of the CCFNI; concept definition; item review; content and structure
      revision; scale revision; and testing with a sample of the target population.
      METHODS: Data collection methods were aimed at accessing a vulnerable population,
      while enhancing response rate and data quality. A sample of 84 relatives of
      critically ill patients from one Melbourne Metropolitan Emergency Department was
      used, 73% of whom returned questionnaires. RESULTS: Pilot data were examined with
      the specific purpose of identifying elements of the tool that required refinement
      or modification. Methods used for establishing reliability and validity of the
      revised tool provided satisfactory results. LIMITATIONS: Limitations of this
      study include inadequate sample size for exploratory factor analysis, and an
      incomplete response set for some items, which influenced item analysis.
      CONCLUSION: The process used for addressing the identified methodological issues
      in reviewing and adapting the CCFNI for use in the ED provides a framework for
      adapting an established tool for a specific purpose.

PMID- 14675306
TI  - Response to: 'Editorial: What's the scoop on the nursing shortage' by A.J.
      Tierney (2003) Journal of Advanced Nursing 43(4), 325-326.

PMID- 14675307
TI  - Targeted therapy for epithelial ovarian cancer: current status and future
      prospects.
AB  - Despite advances in surgery and chemotherapy, less than 20% of patients with
      stage III or IV ovarian cancer survive long-term. In the past, cytotoxic regimens
      have been developed empirically, combining active agents at maximally tolerated
      doses, often without a clear rationale for their interaction. Advances in
      understanding the biology of ovarian cancer have identified multiple molecular
      targets that differ in normal and malignant cells. Targets include cell cycle
      regulators, growth factor receptors, signal transduction pathways, molecules that
      confer drug resistance, and angiogenic mechanisms. A number of targeted agents
      have entered clinical trials. Small molecular weight inhibitors, monoclonal
      antibodies, and antisense and gene therapy are all being evaluated alone and in
      combination with cytotoxic drugs. In contrast to earlier studies, the impact of
      each agent on the designated target can be assessed and agents can be matched to
      the genotype and phenotype of malignant and normal cells. In the long run, this
      should facilitate individualization of more effective, less toxic therapy for
      women with ovarian cancer.

PMID- 14675309
TI  - Psychometric evaluation of the Functional Assessment of Cancer
      Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for
      patients receiving systemic chemotherapy.
AB  - The purpose of this study was to validate the Functional Assessment of Cancer
      Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire.
      The FACT/GOG-Ntx is the FACT-G plus an eleven-item subscale (Ntx subscale) that
      evaluates symptoms and concerns associated specifically with chemotherapy-induced
      neuropathy. Two groups of women with ovarian cancer completed the FACT/GOG-Ntx:
      one group with known neurotoxicities and one group of chemotherapy-naive women
      newly diagnosed with ovarian cancer. Levels of patient neuropathy, severity of
      toxicity, and patient quality of life from diagnosis of ovarian cancer to 12
      months post-diagnosis were assessed. The Ntx subscale significantly
      differentiated the two groups at baseline and 3- and 6-month follow-ups,
      demonstrating significantly fewer problems among chemotherapy-naive patients than
      among patients with known neuropathy. The FACT/GOG-Ntx is a reliable and valid
      instrument for assessing the impact of neuropathy on health-related quality of
      life. The Ntx subscale demonstrated sensitivity to meaningful clinical
      distinctions and change over time.

PMID- 14675308
TI  - Optimal therapy of advanced ovarian cancer: carboplatin and paclitaxel vs.
      cisplatin and paclitaxel (GOG 158) and an update on GOG0 182-ICON5.
AB  - Mature results from GOG158 have clearly established carboplatin and paclitaxel as
      an effective and well tolerated standard regimen, providing a basis for the
      reference arm in GOG0182-ICON5, an ongoing multiarmed phase III trial of the
      Gynecologic Cancer InterGroup (GCIG) evaluating the incorporation of newer
      cytotoxic agents. Results from GOG158 will be reviewed, including an analysis of
      second-look surgical outcomes, followed by an update on the current status of
      GOG0182-ICON5.

PMID- 14675310
TI  - Molecular similarities between primary peritoneal and primary ovarian carcinomas.
AB  - The objective of this paper was to characterize expression patterns of biologic
      markers to distinguish papillary serous peritoneal carcinoma (PPC) from papillary
      serous ovarian carcinoma (POC). Immunohistochemical analysis of HER-2/neu, p53,
      bcl-2, and nm23-H1 expression was performed on archival paraffin-embedded
      tissues. Antigen expression was compared at ovarian and extra-ovarian sites.
      Thirty-two PPC cases were compared to 18 POC cases. Mean age, stage, grade, and
      survival outcome were comparable between the two groups. Antigen expression
      patterns were not significantly different between PPC and POC for the four
      markers studied. In all cases, nm23-H1 was expressed. Conversely, bcl-2 was
      expressed at only a single tissue site in three of 32 (9.4%) PPC cases and in one
      of 18 (5.6%) POC cases. Eleven of 32 (34.4%) PPC cases overexpressed HER-2/neu,
      vs. four of 18 (22.2%) POC cases. P53 staining results were positive in 23 of 32
      (71.9%) PPC and 13 of 18 (72.2%) POC cases. Intrapatient antigen expression was
      identical at primary and metastatic tumor sites in 50% of the POC and 48.4% of
      the PPC cases. We conclude that PPC and POC have a comparable immunohistochemical
      phenotype for these four molecular markers, which is reflected by their similar
      clinical courses.

PMID- 14675311
TI  - Factors associated with non-epithelial ovarian cancer among Mexican women: a
      matched case-control study.
AB  - The purpose of this study was to identify risk factors associated with the
      development of non-epithelial ovarian cancer in Mexican women. A case-control
      study was carried out on women registered with the Mexican Institute of Social
      Security in Mexico City over a period of two years (1995-97). Twenty-eight new
      cases were recruited from the Gynecology and Obstetrics Hospital no. 4, "Luis
      Castelazo Ayala", and were matched by age with 84 controls selected randomly.
      Eighteen (64.3%) cases of germ cell tumors and 10 (35.7%) stromal sex cord tumors
      were found. The number of full term pregnancies was associated inversely to
      development of stromal sex cord tumors with lower risk in women with more than
      three full term pregnancies (odds ratio, 0.02: 95% confidence interval, 0.001
      0.56) compared to nulliparous women. No associations were found respecting to
      germ cell tumors. Parity was inversely associated to development of stromal sex
      cord tumors, probably as a result of the endocrine system's influence on the
      ovaries. The development of germ cell tumors could be associated to factors not
      evaluated in this study.

PMID- 14675312
TI  - Long-term results of cytoreductive surgery for advanced and recurrent epithelial
      ovarian cancers and papillary serous carcinoma of the peritoneum.
AB  - The aim of this study was to review the long-term results of cytoreductive
      surgery in the treatment of advanced primary and recurrent epithelial ovarian
      cancers and papillary serous carcinoma of the peritoneum. Our goal was to
      identify clinical factors by which to select patients likely to benefit from a
      comprehensive management plan. Clinical data of 28 females who underwent surgery
      were retrieved from a prospective database. Major cytoreductive procedures were
      possible in 25 patients. Heated intraoperative or early postoperative
      intraperitoneal chemotherapy was also used where appropriate. The median follow
      up after cytoreduction was 26.9 months. The overall median survival after
      cytoreduction was 45.8 months. The prognostic indicators associated with a
      statistically significant impact on survival were the Prior Surgery Score (P <
      0.001), the Completeness of Cytoreduction Score (P = 0.037) and response to
      chemotherapy prior to surgery (P = 0.012). Our findings suggest that
      cytoreductive surgery can be effective when combined with perioperative
      intraperitoneal chemotherapy. Results can be improved by excluding cases where
      completeness of cytoreduction seems unlikely. Extensive prior surgery without the
      protection of adjunctive intraperitoneal chemotherapy is associated with a poor
      prognosis. This may be due to disruption of anatomic planes leading to deep
      abdominal and pelvic dissemination intractable to further treatment.

PMID- 14675313
TI  - Comparison of HGF (hepatocyte growth factor) levels of epithelial ovarian cancer
      cyst fluids with benign ovarian cysts.
AB  - Hepatocyte growth factor (HGF) is known to take a role in oncogenesis and tumoral
      behavior of the tumors of the organs that contain both mesenchymal and epithelial
      cells. This study compares HGF levels in cyst fluids of epithelial ovarian cancer
      and benign ovarian cysts to look for the role of HGF in ovarian carcinogenesis.
      Twenty-four consecutive patients with ovarian cancer and 34 with benign ovarian
      cysts were recruited prospectively at the Gynecologic Oncology Departments of SSK
      Ankara Maternity Hospital and Hacettepe University School of Medicine between
      2001 and 2002. Cyst fluids were collected during primary staging in cancer
      patients and during laparatomy for benign patients. HGF levels were measured by
      ELISA method. Median HGF levels of the benign ovarian cysts and epithelial
      ovarian tumoral fluids were found to be 3822 pg/ml (85-15253 pg/ml) and 12962
      pg/ml (4136-16025 pg/ml), respectively. Malignant cyst fluids have higher HGF
      levels when compared with benign ovarian cysts (P < 0.01). This finding suggests
      that HGF may take a paracrine role in oncogenic differentiation and tumoral
      development of epithelial ovarian cancers. Mechanisms that take a role in HGF
      secretion and the responses of neighboring epithelial cells to HGF during tumoral
      development need to be investigated.

PMID- 14675314
TI  - Multivariate analysis for prognostic significance of histologic subtype, GST-pi,
      MDR-1, and p53 in stages II-IV ovarian cancer.
AB  - It has been suggested that histologic subtype of ovarian cancer is a factor that
      determines the chemoresponsiveness of tumor. In this study, we wanted to clarify
      the prognostic significance of histologic subtype and its correlation to
      expression of chemoresistance-related proteins (CRPs) in ovarian cancer. A total
      of 93 stage II-IV ovarian cancers, where the proportion of serous, endometrioid,
      mucinous, and clear cell subtype was 61.3%, 14.0%, 7.5%, and 17.2%, respectively,
      were investigated for glutathione S-transferase-pi (GST-pi), MDR (multidrug
      resistance)-1, and p53 expression using immunohistochemistry. GST-pi expression
      was detected in 62.4% of the tumors and was not related to histologic subtype of
      tumor. MDR-1 expression was observed in 12.9% of the tumors tested and was more
      frequently detected in clear cell adenocarcinomas than other histologic subtypes
      of tumor (10/ 16 vs. 2 / 77, P < 0.001). P53 expression was found in 49.1% of
      serous, 53.8% of endometrioid, and 50% of mucinous adenocarcinomas. In contrast,
      none of 16 clear cell adenocarcinomas showed positive p53 staining. In univariate
      analysis, no direct correlations were found between CRPs and overall survival.
      Histology of mucinous/clear cell tumors (P = 0.0063), as well as FIGO stage
      III/IV (P = 0.0091) and residual tumor >or= 2 cm (P = 0.0045), was found to have
      independent prognostic value in multivariate analysis. In conclusion, histologic
      subtype proved to be the significant independent prognostic factor in addition to
      FIGO stage and residual tumor in stage II-IV ovarian cancer. GST-pi, MDR-1, and
      p53 expression pattern is closely related to histologic subtype of ovarian
      cancer, although they are not significant predictors of survival.

PMID- 14675315
TI  - CYP1A1 polymorphism and risk of gynecological malignancy in Japan.
AB  - The incidence of endometrial cancer and ovarian cancer in Japan has been
      increasing in recent years. Results of epidemiologic studies suggest that the
      onset and multiplication of these cancers are associated with estrogen. Estrogens
      are metabolized by cytochrome P450 1A1 (CYP1A1) and converted into
      catecholestrogens, which are carcinogens. CYP1A1 has several polymorphisms, the
      major one being T6235C transition in the non-coding 3'-flanking region (MspI
      polymorphism), and another being A4889G transition in exon 7 (Ile/Val
      polymorphism). These polymorphisms can affect the metabolites of estrogens and
      contribute to the susceptibility to gynecological malignancy. In this study, to
      determine whether CYP1A1 polymorphism plays a role in the development of
      gynecological malignancy in the Japanese population, we assessed the association
      of CYP1A1 polymorphism in Japanese patients with gynecological malignancy in
      comparison to that in controls. The odds ratios (ORs) of Ile/Val polymorphism
      were 1.16 in ovarian cancer patients and 1.70 in endometrial cancer patients. The
      ORs of MspI polymorphism were 1.33 in ovarian cancer patients and 0.88 in
      endometrial cancer patients. No significant association was found between these
      CYP1A1 polymorphisms and gynecological malignancy. Although the frequency of
      CYP1A1 polymorphism in the Japanese population is higher than that in the
      Caucasian population, CYP1A1 polymorphism is not related to gynecological
      malignancies in Japanese population.

PMID- 14675316
TI  - Total mesometrial resection: high resolution nerve-sparing radical hysterectomy
      based on developmentally defined surgical anatomy.
AB  - Total mesometrial resection (TMMR) is characterized by: i). the en bloc resection
      of the uterus, proximal vagina, and mesometrium as a developmentally defined
      entity; ii). transection of the rectouterine dense subperitoneal connective
      tissue above the level of the exposed inferior hypogastric plexus; and iii).
      extended pelvic/periaortic lymph node dissection preserving the superior
      hypogastric plexus. Since July 1998 we have studied prospectively the outcome in
      patients treated with TMMR for cervical carcinoma FIGO stages IB, IIA, and
      selected IIB. By July 2002, 71 patients with cervical cancer stages pT1b1 (n =
      48), pT1b2 (n = 8), pT2a (n = 3), pT2b (n = 12) had undergone TMMR without
      adjuvant radiation. Fifty-four percent of the patients exhibited histopathologic
      high risk factors. At a median observation period of 30 months (9-57 months) two
      patients relapsed locally, two patients developed pelvic and distant recurrences
      and two patients only distant recurrences. Three patients died from their
      disease. Grade 1 and 2 complications occurred in 20 patients, no patient had
      grade 3 or 4 complications. No severe long-term impairment of pelvic visceral
      functions related to autonomic nerve damage was detected. Based on these
      preliminary results, we believe TMMR achieves a promising therapeutic index by
      providing a high probability of locoregional control at minimal short and long
      term morbidity.

PMID- 14675317
TI  - A real time optoelectronic device as an adjunct to the Pap smear for cervical
      screening: a multicenter evaluation.
AB  - We report on the results from a multicenter trial for a real time optoelectronic
      device as an adjunct to the Pap smear for cervical screening. TruScreen
      (Polartechnics Limited, Sydney, Australia) is an automated device which measures
      the response to optical and electrical stimulation of the cervix and returns a
      screening result in real time. Analysis was performed on a group of 651 subjects
      recruited at 10 centers. Cytology and histology analyses were performed by
      centralized laboratories, with the cytology classification performed according to
      the Bethesda 2001 system. The sensitivities for histologically confirmed CIN 2/3
      lesions by TruScreen, Pap, and TruScreen/Pap combined were 70% (95% CI: 67-74),
      69% (CI: 65-72), and 93% (CI: 91-95), respectively. For histologically reported
      CIN 1, the sensitivities of the TruScreen, Pap, and combined test were 67% (CI:
      63-70), 45% (CI: 41-49), and 87% (CI: 84-89). The improvement in sensitivity for
      the combined test compared to the Pap smear alone was significant (P = 0.002).
      Because TruScreen and cytology detect partly different but overlapping groups of
      CIN cases, the adjunctive combination provides very high CIN detection rates.

PMID- 14675318
TI  - A new technique to map vulva microcirculation using laser Doppler perfusion
      imager.
AB  - The location of the vulva has had limited technologic progress in the assessment
      of the skin microcirculation and its application to clinical practice. Our group
      previously demonstrated increased perfusion in vulvar cancer compared to adjacent
      uninvolved skin with the laser Doppler flowmetry (LDF). The LDF is severely
      limited by its low spatial resolution ( approximately 1 mm(2)) and pressure
      involved in positioning of the probe, which may affect value of the underlying
      tissue perfusion. Topographic perfusion mapping of the whole vulvar skin using
      LDF is also time consuming and is not clinically practical. We describe for the
      first time the application of the novel laser Doppler perfusion imager (LDPI) to
      map vulvar skin blood flow and give example in two cases with well-defined vulvar
      pathology-psoriasis and lichen sclerosus with invasive neoplasia-and discuss the
      potential of LDPI to study vulvar skin blood flow.

PMID- 14675319
TI  - Shanxi Province cervical cancer screening study II: self-sampling for high-risk
      human papillomavirus compared to direct sampling for human papillomavirus and
      liquid based cervical cytology.
AB  - The objective of this study was to compare the sensitivity and specificity of a
      new method for self-sampling for high risk human papillomavirus (HPV) with direct
      sampling and liquid based cervical cytology. In Shanxi Province, China, 8,497
      women (ages 27-56) underwent a self-sample for HPV using a conical-shaped brush
      placed into the upper vagina and rotated. Three to sixteen months later the women
      were screened with liquid-based cytology and direct HPV tests. Subjects with any
      abnormal test underwent colposcopy and multiple biopsies. Mean age was 40.9
      years. 4.4 percent of subjects had >or=CIN II, 26% a positive self-sample and 24%
      a positive direct test for HPV. The sensitivity for detection of >or=CIN II was
      87.5% for self-sampling, and 96.8% for the direct test (P < 0.001). The
      specificity was 77.2% for the self-sample and 79.7% for the direct test. With an
      abnormal Pap defined as ASCUS or greater the sensitivity of the Pap for the
      detection of >CIN II was 88.3% and the specificity was 81.2%. We conclude that
      self-sampling for HPV is less sensitive for >CIN II than the direct test, but
      similar to liquid based cytology.

PMID- 14675320
TI  - Knowledge and practice about cervical cancer and Pap smear testing among patients
      at Kenyatta National Hospital, Nairobi, Kenya.
AB  - Invasive cervical cancer (ICC) is the leading cause of cancer-related death among
      women in developing countries. Population-based cytologic screening and early
      treatment does reduce morbidity and mortality associated with cervical cancer.
      Some of the factors related to the success of such a program include awareness
      about cervical cancer and its screening. The objective of this study was to
      assess knowledge and practice about cervical cancer and Pap smear testing among
      cervical cancer and noncancer patients using a structured questionnaire to obtain
      information. Fifty-one percent of the respondents were aware of cervical cancer
      while 32% knew about Pap smear testing. There were no significant differences in
      knowledge between cervical cancer and noncancer patients. Health care providers
      were the principal source of information about Pap testing (82%). Only 22% of all
      patients had had a Pap smear test in the past. Patients aware of cervical cancer
      were more likely to have had a Pap smear test in the past. The level of knowledge
      is low among ICC and noncancer patients. There is need to increase the level of
      knowledge and awareness about ICC and screening among Kenyan women to increase
      uptake of the currently available hospital screening facilities.

PMID- 14675321
TI  - The interaction between steroid hormones, human papillomavirus type 16, E6
      oncogene expression, and cervical cancer.
AB  - Various risk factors have been implicated in the causation of cervical cancer
      including human papillomavirus (HPV), the early genes (E6 and E7 ) of which
      encode the main transforming proteins. Studies have suggested that steroid
      hormones may enhance the expression of these genes leading to loss of p53 gene
      mediated cell apoptosis. A total of 120 cervical tissue samples were obtained
      from patients with proven cervical cancer. Patients who used depo
      medroxyprogesterone acetate steroid contraception were recruited as part of the
      steroid arm. Only HPV DNA type 16 samples were used for the study. Controls
      included three cell lines (CaSki, SiHa, & C33A) and glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) was used as an internal housekeeping gene. Of 120 patients,
      there were 111 patients with HPV type 16 identified. Of this number, RNA was
      present in 63 samples. There were 30 women (30/63) who used steroid
      contraception. In relation to patients who used contraception, HPV 16 E6 gene
      expression was present in 79% (n = 23) and 88% (n = 30) of steroid users compared
      to nonusers, respectively. In total there were 25 patients (40%) with expression
      of the HPV 16 E6*I gene and 30 patients with expression of the E6*II gene. There
      were 57% of steroid users (n = 17) who had expression of the E6*I/E6*II gene,
      compared to 52% (n = 17) of nonusers (P = 0.800). From a molecular level, this
      study does not confirm the role of injectable progesterones in cervical
      carcinogenesis.

PMID- 14675322
TI  - The effect of codon 98 of the FHIT gene on cervical cancer in Korean women.
AB  - The Fragile Histadine Triad (FHIT) is a putative tumor suppressor gene involved
      in different tumors. The objective of this study was to examine the effect of
      codon 98 of FHIT on cervical carcinogenesis. The study subjects were patients who
      were pathologically diagnosed with cervical neoplasia and who had a positive
      result for human papillomavirus (n = 567) compared to normal healthy women as
      normal controls (n = 506). The FHIT-specific sequences of DNA from peripheral
      blood samples from study subjects were determined by PCR using allele-specific
      primers and were compared with those of the controls. The genetic susceptibility
      of codon 98 of the FHIT gene (3p14.2) in cervical carcinogenesis was determined
      by examining the effect of the gene and environmental factors vs. the different
      stages of cervical intraepithelial lesions and the different histopathologic
      types of invasive cervical cancers. On assessing FHIT polymorphisms, the
      percentages of individuals homozygous for the T allele, homozygous for the C
      allele, and heterozygous for these two alleles were 42.1%, 11.3, and 46.6% in the
      control group. The corresponding figures were 39.5%, 14.8%, and 45.7% among in
      women with cervical cancer. Compared with FHIT T/ T, odds ratio (95% confidence
      interval) for FHIT C/C was 1.4 (0.8-2.5) for invasive cervical cancer and 1.7
      (0.9-3.1) for cervical intraepithelial neoplasia (CIN) II or III. The risks for
      invasive cervical cancer were higher with early onset cervical carcinogenesis
      (2.3, 1.0-5.5, P = 0.0438), than with late onset (1.0, 0.5-2.1, P = 0.9306). The
      risks of FHIT C/C or C/ T also increased for ever smokers or women with two or
      more children compared with FHIT T/ T. Polymorphisms of FHIT are associated with
      a higher risk of developing cervical cancer, in particular early onset cervical
      carcinogenesis.

PMID- 14675323
TI  - Prognostic significance of c-erbB-2/HER2 expression in advanced uterine cervical
      carcinoma with para-aortic lymph node metastasis treated with radiation therapy.
AB  - This paper looks at whether c-erbB-2/HER2 expression in uterine cervical
      carcinoma before treatment is a predictive parameter of prognosis in patients
      with para-aortic lymph node metastasis (PALN) in advanced disease after treatment
      with radiation therapy (RT). Twenty-one patients with PALN at the first visit
      and/or during follow-up and treated with RT for PALN lesions were studied. Their
      clinical stages were IIIB or greater and they were referred to the National
      Institute of Radiological Sciences Hospital for RT between 1987 and 1995. They
      consisted of 12 patients with PALN detected at the first visit and nine with PALN
      detected during the follow-up period. All patients had no distant metastasis
      except PALN. They were treated with a combination of external whole pelvis and
      intracavitary irradiation to the primary pelvic lesions. The PALN was treated
      with external irradiation alone with anterior-posterior parallel opposed fields
      and anterior oblique fields or anterior-posterior parallel opposed oblique
      fields. The average total dose to PALN was 53.3 Gy (40-61Gy). Tissue samples were
      obtained from cervical tumors (primary lesions) before RT. Immunohistochemical
      staining was performed using anti-c-erbB-2/HER2 monoclonal antibody for
      conventional paraffin sections. c-erbB-2/HER2 positive staining was observed in
      cancer membrane and cytoplasm. Nine specimens were positive for c-erb-B2/HER2 and
      the total positive rate was 43%. The 5-year survival rate was 38% for all
      patients. The 5-year survival rate of the c-erbB-2/HER2 positive patients was
      28%, representing a trend toward poorer prognosis than the 52% of negative
      patients (P = 0.10). Multivariate analysis using Cox proportional hazards model
      showed that c-erbB-2/HER2 was an independent prognostic factor (P = 0.024). The
      present study suggests that c-erbB-2/HER2 expression of cervical tumors might be
      a predictive parameter of prognosis after radiation therapy for PALN of very
      advanced uterine cervical carcinoma patients.

PMID- 14675324
TI  - Significance of microvascular density (MVD) in cervical cancer recurrence.
AB  - The purpose of this retrospective study of 118 patients with squamous cell
      cervical cancer from January 1990 to December 1993 was to evaluate angiogenesis
      as predictive factor of recurrence in cervical cancer stages II-III treated with
      standard radiotherapy. Microvessel density (MVD) was evaluated and correlated
      with other prognostic factors. MVD was greater than 20 in 67.8% of patients with
      recurrence (P = 0.002) in comparison to 39% of patients without. Disease-free
      survival was shorter in stage IIA and MVD >20 (P = 0.0193) as well as for stage
      IIB (P < 0.05 ), but not for IIIB (P = 0.1613 ). Global survival was
      significantly shorter when MVD was >20 (P = 0.0316). For stage IIA and MVD >20
      survival was shorter (P = 0.0008) for stage IIB (P < 0.05) but not for IIIB (P =
      0.14). Patients younger than 40 years and MVD >20 had poorer disease-free
      interval and survival (P = 0.0029). MVD in patients with squamous cell cervical
      cancer stage II and age younger than 40 may play a role in predicting recurrence
      and survival.

PMID- 14675325
TI  - The value of pelvic and para-aortic lymphadenectomy in endometrial cancer to
      avoid unnecessary radiotherapy.
AB  - The case histories of 95 patients with endometrial carcinoma treated between July
      1998 and December 2002 were reviewed. These patients were staged according to
      FIGO classification and included peritoneal cytology, total abdominal
      hysterectomy/bilateral salpingo-oophorectomy (TAHBSO), and pelvic with or without
      para-aortic lymphadenectomy. The FIGO surgical stages were as follow: IA, 9
      (9.5%); IB, 35 (36.8%); IC, 16 (16.8%); IIB, 10 (10.5%); IIIA, 5 (5.3%); IIIB, 1
      (1.1%); IIIC, 19 (20.0%). In addition to TAHBSO, 47 (49.5%) patients had pelvic
      lymphadenectomy whereas 48 (50.5%) had both pelvic and para-aortic
      lymphadenectomy. Nineteen (20.0%) of 95 patients had nodal metastases. Positive
      pelvic and para-aortic lymph nodes were found in 15 (15.8%) of 95 and 12 (25.0%)
      of 48 patients, respectively. According to the result of the lymphadenectomy, 19
      (20.0%) patients had their surgical stage upgraded to stage IIIC and 61 (64.2%)
      patients had a change in their management plan. Twelve (12.6%) patients required
      extended field irradiation due to para-aortic nodal metastases and 49 (51.6%)
      patients with negative nodes avoided postoperative external radiotherapy. By
      defining the lymphatic spread via surgical staging, postoperative radiotherapy
      can be recommended to patients with nodal metastases, while it can be withheld
      from those patients with negative nodes, irrespective of the presence of risk
      factors.

PMID- 14675326
TI  - Oncoprotein profiles of primary peritoneal malignant mixed mullerian tumors.
AB  - Primary peritoneal malignant mixed mullerian tumors (MMMTs) are extremely rare
      and highly aggressive malignancies associated with poor clinical prognoses. We
      present a clinicopathologic review of three cases of this rare tumor by examining
      expression of selected oncoproteins by immunohistochemistry. Three consecutive
      cases of primary peritoneal MMMT were examined by paraffin immunohistochemistry
      for expression of p53, p16, BCL2, CerbB2, and classical cadherins E-cadherin, P
      cadherin, and N-cadherin. All three cases expressed p16, but showed less
      consistent expression of other markers, with one case expressing p53 and one
      expressing BCL2. All cases were negative for membrane expression of Cerb-B2. The
      three classical cadherins were expressed in two cases with one case showing only
      weak N- and P-cadherin expression. No difference in antigen expression was seen
      in the epithelial compared to sarcomatous components. We conclude that p16 may be
      a common tumor suppressor gene expressed in peritoneal MMMT. P53 overexpression
      may be of lesser frequency in peritoneal MMMT compared to MMMT from the ovary and
      the uterus. We did not observe any difference in antigen expression between areas
      of epithelial or sarcomatous differentiation, which would support a single
      pluripotential malignant clone in the histogenesis of these tumors.

PMID- 14675327
TI  - Gestational trophoblastic syndrome and human immunodeficiency virus (HIV)
      infection: a retrospective analysis.
AB  - The appropriate management of gynecological malignancies in association with
      human immunodeficiency virus (HIV) infection is not established. To date the
      reported literature on the subject consists mainly of case reports. Due to the
      increasing prevalence of HIV infection, especially in sub-Saharan countries, the
      chances of finding both conditions in the same patient has produced management
      and ethical dilemmas. This retrospective study describes the management of 12 HIV
      infected patients and compares their outcome with 29 non HIV-infected patients.
      The mean age of the non HIV-infected patients was 30 years (range 16-56 years),
      while the mean age of the HIV-infected patients was 32 years (range 20-47 years).
      In terms of risk factors, there were 72% of non HIV-infected women in the high
      risk category compared to 50% of HIV-infected women (P = 0.468). All patients who
      received treatment had CD4 counts greater than 200 cells/microl. Two HIV-infected
      women who did not receive any form of chemotherapy due to low CD4 counts (41
      cells/microl and 84 cells/microl) demised of their disease. The majority of women
      (86% non HIV-infected & 90% HIV-infected) received lfewer than 10 cycles of
      chemotherapy to attain cure. Most side effects were minor. None of the HIV
      infected patients who received chemotherapy demised of their disease. In total,
      irrespective of risk category, there were 38 patients (93%) who were cured of
      their disease by chemotherapy including 10 HIV-positive patients. All patients
      were alive and free of disease at their last follow-up visit. Although the
      numbers are small, it is proposed that HIV-infected patients with choriocarcinoma
      and a reasonable degree of CD4 counts (>200cells/microl) should receive standard
      therapy.

PMID- 14675328
TI  - Methylation status and expression of E-cadherin and cadherin-11 in gestational
      trophoblastic diseases.
AB  - The clinical significance of cadherins in gestational trophoblastic diseases
      (GTD) is not fully understood. In this study, the expression of E-cadherin and
      cadherin-11 in 12 normal placentas, 32 cases of hydatidiform mole (HM) including
      15 complete HMs and 17 partial HMs, and five choriocarcinomas was investigated by
      immunohistochemistry and correlated with follow-up of HMs. Cases with available
      frozen blocks were further analyzed by western blot and semiquantitative reverse
      transcriptase polymerase chain reaction (RT-PCR). Methylation of E-cadherin was
      investigated by methylation-specific PCR in six normal first trimester placentas,
      19 HMs and their associated deciduas. E-cadherin expression was localized to
      cytotrophoblast and intermediate trophoblast whereas cadherin-11 was expressed in
      syncytiotrophoblast, intermediate trophoblast, and decidua. Immunoreactivity of E
      cadherin was reduced in choriocarcinoma and complete HM when compared with that
      in normal first trimester placenta (P < 0.01, P = 0.04). Hypermethylation of E
      cadherin was demonstrated in three complete HMs with the lowest level of E
      cadherin. Compared with normal first trimester placenta, immunoreactivity of
      cadherin-11 was higher in complete HM (P = 0.02), but lower in choriocarcinoma (P
      = 0.02). Such differential expression was confirmed by western blot and
      semiquantitative RT-PCR. No obvious association was observed between the
      development of persistent trophoblastic disease with the expression of E-cadherin
      and cadherin-11.

PMID- 14675329
TI  - A study of blood cross-matching requirements for surgery in gynecological
      oncology: improved efficiency and cost saving.
AB  - The objective of this study was to design and implement a maximum surgical blood
      order schedule (MSBOS) within a specialist gynecological oncology department in a
      tertiary referral center and evaluate its impact on the cross-match to
      transfusion ratio (CTR). A retrospective case note audit was undertaken to
      identify common operations performed within the unit and their transfusion
      requirements. The efficiency of blood usage was assessed using the CTR, and an
      MSBOS was devised and implemented. A prospective audit of preoperative blood
      cross-matching and subsequent blood usage was then performed for consecutive
      elective operations in the unit, to assess the effect of the MSBOS. The
      retrospective study of 222 cases demonstrated a CTR of 2.25 equivalent to 44%
      usage of cross-matched blood. Ninety two percent of operations performed within
      the unit could be incorporated into an MSBOS. The prospective study of 207 cases
      demonstrated a significantly reduced CTR of 1.71 or 59% blood usage (chi2 = 12.4,
      P < 0.001). This equates to a saving of 102 units of blood over the 15 months
      prospective audit. Protocol adherence was 77%. No patient was adversely affected
      by the adoption of the MSBOS. We conclude that an MSBOS can be safely introduced
      into a gynecological oncology department resulting in significant financial
      savings.

PMID- 14675330
TI  - Uterine inversion by a mixed mullerian tumor of the corpus.
AB  - Mixed mullerian tumors (MMT) of the uterus have been reported following the use
      of tamoxifen. Rarely, these tumors lead to an uterine inversion. The surgical
      approach of a uterine inversion forms a therapeutic challenge. In this article, a
      case of uterine inversion due to a MMT is reported, together with a literature
      review regarding the developing mechanisms and management.

PMID- 14675331
TI  - Complete and sustained remission of refractory cervical cancer following a single
      cycle of capecitabine. A case report.
AB  - Cervical cancer with distant metastasis is almost always incurable. The treatment
      goal is to palliate the patient's symptoms with pain medications and localized
      radiation therapy. Chemotherapy generally has a limited role, with responses that
      are short lived. Newer agents investigated as potential therapy include
      fluorouracil prodrugs. We report on a case where capecitabine was used in
      metastatic cervical cancer with progression of disease outside the radiation
      field, following multiple drug regimens including one dose of cisplatin
      (discontinued due to transient renal toxicity), paclitaxel, and carboplatin and
      continuous infusion 5-fluorouracil (5-FU) The patient was treated with
      capecitabine 1100 mg/m2 twice daily for two weeks. After the first week of the
      cycle, the patient developed grade 2 toxicities consisting of mucositis and hand
      foot Syndrome but she continued on therapy through day 14. On day 20 she was
      hospitalized with grade 4 toxicity, which included febrile neutropenia, urinary
      tract infection, pancytopenia, mucositis, hand-foot syndrome, and renal failure,
      all of which have subsequently completely resolved. Restaging demonstrated
      complete remission. Although the patient suffered toxicity related to
      capecitabine, 3.5 years post a single cycle of capecitabine, the patient remains
      in remission, with no evidence of disease reoccurence.

PMID- 14675332
TI  - Endometrial carcinoma with recurrence in the incisional scar: a case report.
AB  - We report a case of papillary adenocarcinoma of uterus which developed a
      recurrence over the scar of surgery. The patient initially underwent surgery
      followed by adjuvant chemoradiotherapy for her stage II disease. She was disease
      free until 21 months when she developed a small mass over the lower site of
      incisional scar. Fine needle aspiration cytology from this swelling revealed
      metastatic papillary adenocarcinoma similar to previous histopathology. Treatment
      of the scar recurrence consisted of palliative radiation therapy and
      chemotherapy.

PMID- 14675333
TI  - Acute leukemia in pregnancy with ovarian metastasis: a case report and review of
      the literature.
AB  - Acute leukemias tend to affect a younger population and are much more common in
      pregnant patients than chronic leukemias are. We report a case of acute
      lymphoblastic leukemia diagnosed during the third trimester presenting with
      organomegaly and thrombocytopenia. Delivery of the fetus by cesarean section was
      decided because of the fulminant nature of the acute leukemia within days of
      admission. Bone marrow biopsy revealed acute lymphocytic leukemia, French
      American-British L2 subtype B cell immunotype. A left ovarian mass was identified
      during the cesarean section which later proved to be lymphoblastic infiltration.
      The patient was started on induction chemotherapy consisting of vincristine,
      daunorubicin, prednisolone, and l-asparaginase immediately after the diagnosis.
      The patient died of Acinetobacter septicemia 18 days after the first admission.

PMID- 14675334
TI  - Endometrial cancer metastasis presenting as a grossly swollen toe.
AB  - Metastasis to the peripheral skeleton, especially in the face of low stage
      disease, is rare. This report describes the case of a 77-year-old lady with stage
      IC disease who underwent curative total abdominal hysterectomy and bilateral
      salpingo-oopherectomy 2 years prior to presenting with a painless gigantism of
      her fourth toe. A histologic diagnosis of dedifferentiated endometrial metastasis
      with sarcomatous differentiation was made following amputation of the toe.
      Osseous metastasis to bone is discussed in the context of endometrial carcinoma
      and the literature reviewed. This paper reports the first case of endometrial
      carcinoma metastasis presenting as gross swelling of a toe.

PMID- 14675335
TI  - Patient selection for neoadjuvant chemotherapy trials.

PMID- 14675336
TI  - Laterally extended parametrectomy (LEP), the technique for radical pelvic side
      wall dissection: Feasibility, technique and results.
AB  - A new surgical method was introduced for the treatment of Ib lymph node positive
      and IIb cervical cancer patients. The lateral resection plane corresponds to the
      true pelvic side wall, the plane represented by the internal obturator muscle,
      the linea arcuata, and the piriformis muscle with the convergent branches of the
      sacral plexus. The LEP procedure overcomes the limitations of the standard class
      III-IV radical hysterectomy, which leaves in situ the gluteal superior, inferior
      and pudendal nodes, thus improving local control and survival.

PMID- 14675338
TI  - Immunohistochemistry in gynecological pathology.
AB  - Although the majority of diagnoses in gynecological pathology are established on
      examination of routine hematoxylin and eosin stained sections, additional tests
      are occasionally required. Immunohistochemistry is widely used to provide
      additional diagnostic information in problematic cases. This review touches on
      some of the basics of the procedure, presents an example immunohistochemical
      panel, and discusses some of the most common immunohistochemical markers used in
      diagnostic gynecological pathology. Differential diagnostic problems and relevant
      immunohistochemical stains for the vulva, vagina, cervix, uterus, and ovary are
      also addressed.

PMID- 14675339
TI  - Chemoradiation: A new approach for the treatment of cervical cancer.
AB  - Despite advances in screening, cervical cancer remains a major health problem
      worldwide. In an effort to improve loco-regional control, both neoadjuvant and
      chemoradiation have been trialed. Recently, five randomized clinical trials
      performed by the Gynecologic Oncology Group, the Radiation Therapy Oncology Group
      and the Southwest Oncology Group have demonstrated a significant advantage both
      in progression-free and overall survival when cisplatin-based chemotherapy was
      administered during radiation for advanced stages of cervical cancer. Based on
      the results of these trials, the US National Cancer Institute released a Clinical
      Announcement supporting the concurrent use of cisplatin-based chemotherapy with
      radiation therapy for high-risk early stage and locally advanced stage cervical
      cancer. Subsequently, an additional prospective randomized trial performed by the
      National Cancer Institute of Canada was not able to show benefit with the use of
      chemoradiation compared with radiation alone for patients with locally advanced
      stage cervical cancer. This article will analyze these six clinical trials in
      order to determine the role of chemoradiation in the management of patients with
      cervical cancer. Furthermore, as anemia is one of the most powerful prognostic
      factors in patients with cervical cancer, we propose to evaluate the relationship
      between a decreased level of hemoglobin and treatment outcome.

PMID- 14675340
TI  - Neoadjuvant chemotherapy for FIGO stage III or IV ovarian cancer: Survival
      benefit and prognostic factors.
AB  - The survival benefit of neoadjuvant chemotherapy (NAC) was assessed in patients
      with FIGO stage III or IV ovarian cancer, and the prognostic value of various
      therapeutic factors was determined. In patients treated for stage III or IV
      ovarian malignancies at the Department of Obstetrics and Gynecology of Nagoya
      University or related institutions between 1987 and 1996, 119 had a histologic
      diagnosis of serous cystadenocarcinoma. For this group, the long-term outcome was
      compared between 96 patients receiving conventional adjuvant chemotherapy
      following standard surgery and 23 patients treated with NAC, both followed by a
      second cytoreductive surgery. In a total of 29 patients with all histologic types
      of malignancy, the tumor response to NAC and survival were analyzed on the basis
      of histology, chemotherapy regimen, residual tumor size after the second
      cytoreductive operation, and the dose intensity of cisplatin. The long-term
      outcome (5-year survival rate) was better in patients treated with conventional
      adjuvant chemotherapy than in patients receiving NAC, although the difference was
      not significant. Overall survival did not differ significantly in relation to
      tumor histology or chemotherapy regimen. With respect to residual tumor size
      after the second surgery, patients with a residual tumor < or = 2 cm in diameter
      had a significantly better prognosis than those with a residual tumor >2 cm. A
      better prognosis was also associated with a higher dose intensity of cisplatin,
      and patients treated at >or = 18 mg/m(2)/week survived significantly longer than
      those receiving <18 mg/m(2)/week.

PMID- 14675341
TI  - Accuracy of frozen section diagnosis in ovarian tumors: Is there a change in the
      course of time?
AB  - A retrospective study of 222 ovarian biopsy results between January 1, 2000 and
      August 31, 2002 was examined to determine the accuracy of frozen section
      diagnosis. In addition we reviewed all previous studies that examined the
      accuracy rates of frozen section diagnosis in ovarian tumors. Histopathologic
      examination results of frozen section biopsies were concordant with paraffin
      diagnosis in 92% of all cases. The sensitivity rates for benign, malignant, and
      borderline ovarian tumors were 98%, 88.7%, and 61%, respectively. There were five
      (2.2%) false-positive (overdiagnosed), and 13 (5.4%) false-negative
      (underdiagnosed) patients in frozen section examination. Frozen section
      examination of mucinous tumors showed higher underdiagnosis rates (20%). Review
      of previous studies showed no significant variation in accuracy rates of frozen
      section diagnosis for benign and malignant ovarian tumors, in relation with time.
      We found low accuracy rates for borderline ovarian tumors which was similar with
      the previous studies. However, there were consistent and relatively higher
      sensitivity rates for borderline ovarian tumors in the recent studies. As a
      result, we conclude that frozen section evaluation in identifying a malignant or
      benign ovarian tumor is accurate enough for the correct diagnosis. Since accuracy
      rates for borderline ovarian tumors are low, we should have more improvement in
      the correct diagnosis.

PMID- 14675342
TI  - Independence of the prognostic value of tumor suppressor protein expression in
      ovarian adenocarcinomas: A multivariate analysis of expression of p53,
      retinoblastoma, and related proteins.
AB  - Accurate estimation of prognosis of ovarian cancer is difficult. For this report,
      in a group of 73 patients with ovarian adenocarcinomas, clinical factors and
      protein expression status of p53, retinoblastoma (Rb), and related proteins were
      evaluated for potential prognostic values. Clinical factors included FIGO stage,
      age, histopathologic type, and protein expression of p53, Rb, MDM2, p14ARF,
      p21WAF(1)/CIP(1) was determined by an immunohistochemical technique. Univariate
      Cox proportional hazard regression analysis was used to determine the significant
      prognostic value of FIGO stage (P < 0.0001), p53 status (0.0021), and patient age
      (P = 0.0255), and we report here, for the first time, the significant (P =
      0.0072) prognostic value of Rb status. Histopathologic type and MDM2, p14ARF,
      p21WAF(1)/CIP(1) status did not show any prognostic value. To examine further the
      independence of prognostic values, we next applied multivariate analysis: We
      found that FIGO stage (P < 0.0001) and p53 status (P = 0.0108) were independent
      prognostic factors, while age and Rb status were not. Independence of prognostic
      value of p53 has heretofore been controversial, but we found a definite
      independent prognostic value for p53 status in ovarian adenocarcinomas. We also
      found that selection of appropriate antibodies for immunohistochemistry was
      essential to obtain significant results. We used five kinds of antibodies for p53
      immunolocalization, and correlation with prognosis was obtained by three of these
      with different grades of statistical significance.

PMID- 14675343
TI  - Intraperitoneal radioimmunotherapy in an ovarian carcinoma mouse model: Effect of
      the radionuclide.
AB  - Despite debulking surgery and multidrug chemotherapy, advanced stage ovarian
      cancer has a high mortality rate. Radioimmunotherapy (RIT) is a treatment
      modality using specific, radiolabeled antibodies that guide cytotoxic
      radionuclides to cancer cells. In the present study, the therapeutic efficacy of
      RIT with murine monoclonal antibody HMFG1 labeled with three different beta
      radiation emitting radionuclides (90Yttrium, 186Rhenium, and 131Iodine) was
      assessed in athymic BALB/c mice with intraperitoneally growing NIH:OVCAR-3
      ovarian carcinoma xenografts. Each of the three intraperitoneally administered
      radiolabeled antibody preparations (90Y-HMFG1, 186Re-HMFG1, and 131I-HMFG1)
      caused a significant delay in ascites formation and mortality as compared to the
      control groups treated with 90Y-labeled irrelevant antibody, nonradiolabeled
      HMFG1, or phosphate buffered saline. Intraperitoneally (ip) administered 90Y
      HMFG1 was shown to have a significantly higher abdominal retention as compared to
      the intraperitoneally administered irrelevant antibody 90Y-G250. Furthermore,
      intraperitoneally administered 90Y-HMFG1 more effectively inhibited tumor growth
      than intravenously administered 90Y-HMFG1. It was concluded that in
      intraperitoneally located malignant disease with ascitic cell clusters and tumor
      deposits, intraperitoneal administration of RIT seemed preferable as compared to
      intravenous administration. The choice of the most optimal radionuclide in
      intraperitoneally located malignancies needs further research, but could well
      depend on tumor characteristics such as the size of the tumor lesions.

PMID- 14675344
TI  - Viability of gynecological malignant cultured cells after 4 degrees C storage in
      citrate-phosphate-dextrose solution.
AB  - For the surgery of gynecological malignant tumors, a predeposit type of
      autologous blood transfusion has been widely used. However, using molecular
      biologic techniques, malignant cells have been found in the peripheral blood of
      cancer patients. Therefore, to evaluate the utility of presurgical blood
      deposits, we studied the survival of gynecological malignant cultured cells after
      4 degrees C storage in citrate-phosphate-dextrose solution. Ten cultured cell
      lines derived from gynecological malignant tumors were used. Mixtures of 1 x 105
      cells, culture medium, and citrate-phosphate-dextrose (CPD) solution were stored
      at 4 degrees C. After 0, 1, 4, 8, 15, or 22 days of storage, cells were placed in
      96-well microtiter plates in culture medium with 1 x 104 cells/100 micro l/well.
      After 24 h culture in the incubator, the survival rate was calculated from the
      optical density by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium
      bromide (MTT) assay. More than 10% of surviving cells were seen in nine cell
      lines after 4 days of storage, in seven cell lines after 8 days, in three cell
      lines after 15 days, and in two cell lines after 22 days. Cancer cells in
      presurgical blood deposits may survive a 3-week storage period at 4 degrees C in
      CPD solution.

PMID- 14675345
TI  - Risk contribution of sexual behavior and cigarette smoking to cervical neoplasia.
AB  - Infection with high-risk human papillomavirus (HPV) is considered a "necessary
      cause" for cervical cancer (CC); however, only some HPV-infected women develop
      CC. We report on the differential risk contribution of sexual behavior and
      cigarette smoking to cervical neoplasia in the US and Venezuela. A total of 142
      patients and 158 matched-controls were recruited from both countries using the
      same recruitment protocol, the same pathologists for case verification, and the
      same experimental procedures for analysis. HPV infection was significantly
      associated with CC for both populations as expected, but the Venezuelan controls
      were twice as likely to be infected with HPV as the US controls. Having >2
      lifetime sexual partners (OR = 4.7, 95% CI = 1.7-13.1) and initiation of sexual
      activities before the age of 18 (OR = 4.7, 95% CI = 1.6-13.7) were significant
      risk factors in a multivariate model for CC in Venezuela. In contrast, current
      cigarette smoking was a significant risk factor only in the US (OR = 3.6, 95% CI
      = 1.7-7.7). The observed differences in risk factors support the need for
      additional studies in different geographic regions and the information can be
      used to develop country-specific CC prevention programs.

PMID- 14675346
TI  - Visual inspection with acetic acid and cytology in the early detection of
      cervical neoplasia in Kolkata, India.
AB  - Visual inspection of the cervix after application of 3-5% acetic acid (VIA) is a
      potential alternative to cytology for screening in low-resource countries. The
      present study evaluated the performance of VIA, magnified visual inspection after
      application of acetic acid (VIAM), and cytology in the detection of high-grade
      cervical cancer precursor lesions in Kolkata (Calcutta) and suburbs in eastern
      India. Trained health workers with college education concurrently screened 5881
      women aged 30-64 years with VIA, VIAM, and conventional cervical cytology.
      Detection of well-defined, opaque acetowhite lesions close to the squamocolumnar
      junction; well-defined, circumorificial acetowhite lesions; or dense
      acetowhitening of ulceroproliferative growth on the cervix constituted a positive
      VIA or VIAM. Cytology was considered positive if reported as mild dysplasia or
      worse lesions. All screened women (N = 5881) were evaluated by colposcopy, and
      biopsies were directed in those with colposcopic abnormalities (N = 1052, 17.9%).
      The final diagnosis was based on histology (if biopsies had been taken) or
      colposcopic findings, which allowed direct estimation of sensitivity,
      specificity, and predictive values. Moderate or severe dysplasia or carcinoma in
      situ (CIN 2-3 disease) was considered as true positive disease for the
      calculation of sensitivity, specificity, and predictive values of screening
      tests. 18.7%, 17.7% and 8.2% of the women tested positive for VIA, VIAM, and
      cytology. One hundred twenty two women had a final diagnosis of CIN 2-3 lesions.
      The sensitivities of VIA and VIAM to detect CIN 2-3 lesions were 55.7% and 60.7%,
      respectively; the specificities were 82.1% and 83.2%, respectively. The
      sensitivity and specificity of cytology were 29.5% and 92.3%, respectively. All
      the tests were associated with negative predictive values above 98%. VIA and VIAM
      had significantly higher sensitivity than cytology in our study; the specificity
      of cytology was higher than that of VIA and VIAM.

PMID- 14675347
TI  - Anemia before and during concurrent chemoradiotherapy in patients with cervical
      carcinoma: Effect on progression-free survival.
AB  - To determine the impact of anemia before and during chemoradiation in patients
      with cervical cancer, we collected data on hemoglobin (Hb) levels before and
      during treatment from 60 unselected patients with cervical carcinoma. All
      patients had FIGO stage IB to IVA disease and were treated with concurrent
      chemoradiation for the aim of cure. Patients with an Hb value below or equal to
      the lower 25th quartile were considered anemic. Progression-free survival (PFS)
      was evaluated by univariate and multivariate analyses. After a median follow-up
      of 26.3 months, 20 patients developed disease progression. The lowest Hb during
      chemoradiation (nadir Hb), the stage of disease, and parametrial involvement were
      correlated significantly with PFS. On multivariate analysis, the nadir Hb
      (relative risk [RR] 0.29) and tumor stage (RR 3.4) remained the only
      prognostically relevant factors predicting PFS. At 60 months the PFS was 39.1%
      for anemic patients and 48.0% for nonanemic patients (P < 0.0002). In patients
      undergoing chemoradiation for cervical carcinoma, a low nadir Hb is highly
      predictive of shortened PFS, whereas the Hb before treatment is prognostically
      not significant.

PMID- 14675348
TI  - The expression and tyrosine phosphorylation of E-cadherin/catenin adhesion
      complex, and focal adhesion kinase in invasive cervical carcinomas.
AB  - The present study aimed to confirm the hypothesis that the expression and
      phosphorylation status of the E-cadherin/catenin adhesion complex is related to
      cervical carcinogenesis and cervical cancer invasion, and to investigate the
      expression and the tyrosine phosphorylation of focal adhesion kinase (FAK) and
      its relation with E-cadherin/catenin adhesion complex. The expression of E
      cadherin, alpha- and beta-catenin, and FAK were studied by a western blot
      analysis with 26 cervical carcinomas, nine normal cervices, and five carcinomas
      in situ of cervix. The tyrosine phosphorylation of alpha- and beta-catenin and
      FAK were examined by an immunoprecipitation. The expressions of alpha- and beta
      catenin and E-cadherin were reduced in cervical carcinoma, and the tyrosine
      phosphorylation of alpha- and beta-catenin in cervical carcinoma was higher than
      in normal cervix and carcinoma in situ of cervix. Tyrosine phosphorylation of FAK
      was elevated in cervical carcinoma although the expression of FAK was not
      significantly different. Moreover, alpha- and beta-catenin were
      coimmunoprecipitated with FAK. We conclude that the loss of E-cadherin/catenin
      proteins and the tyrosine phosphorylation of E-cadherin/catenin are involved in
      cervical carcinogenesis and cancer invasion. Tyrosine phosphorylation of focal
      adhesion kinase is also related to the cervical cancer invasion. The E
      cadherin/catenin complex and FAK may be related functionally and structurally.

PMID- 14675349
TI  - Surgical treatment of lymph node metastases in stage IB cervical cancer: the
      laterally extended parametrectomy (LEP) procedure.
AB  - A surgical method has been introduced for the treatment of early stage cervical
      cancer patients with pelvic lymph node metastases. The procedure was used without
      any adjuvant treatment in 31 stage IB cervical cancer patients, where pelvic
      lymph node metastases were proven by intraoperative histology. Two patients were
      lost for follow-up. Twenty-nine patients were followed up for 24-105 months (mean
      60 months). Twenty-five of 29 patients were alive and disease-free at the end of
      the study period. Kaplan-Meier 5 years cumulative proportion survival was 85% (SE
      7%). Complications in four cases (16%) necessitated a second operation. One
      patient developed treatment-refractory grade II incontinence. All but the one
      incontinent patient are alive without significant treatment related symptoms. The
      results suggest that pelvic lymph node metastases can be cured by surgery alone.
      The LEP procedure seems to be a treatment alternative to chemoradiotherapy for
      early stage cervical cancer patients with pelvic lymph node metastases.

PMID- 14675350
TI  - Phase I clinical trial of chemoimmunotherapy in combination with radiotherapy in
      stage IIIB cervical cancer patients.
AB  - To determine the feasibility and toxicity of a chemoimmunotherapy regimen in
      combination with radiotherapy in stage IIIB cervical cancer patients, cisplatin
      10-20 mg/m(2) intravenous (iv) weekly, 5-fluorouracil (5FU) 500 mg/m(2) (24-h
      infusion) weekly, interferon alpha-2a 3 MU subcutaneously 3 days a week, and 13
      cis-retinoic acid 0.5 mg/kg/day orally were given in concurrence with 8-week
      period of radiotherapy and continued for another 4 weeks after finishing
      radiotherapy. The dose of cisplatin was escalated from 10 mg/m2 in the first
      group of three patients (level 1) to 15 mg/m(2) in the second group of three
      patients (level 2) and to 20 mg/m(2) in the third group of two patients (level 3)
      if the former groups could tolerate the drugs well. Patients in levels 1 and 2
      had tolerable toxicities. Two patients in level 3 experienced grade 4 leukopenia,
      so chemoimmunotherapy was discontinued after 2 and 3 cycles orderly. After
      recovery from toxicities, they continued with radiotherapy. In conclusion,
      cisplatin 15 mg/m2, 5-FU 500 mg/m(2) weekly, interferon alpha-2a 3 MU
      subcutaneously 3 days a week, and 13-cis-retinoic acid 0.5 mg/kg/day orally in
      combination with radiotherapy in stage IIIB cervical cancer patients is
      tolerable. Leukopenia is the dose-limiting toxicity.

PMID- 14675351
TI  - Relation between FIGO stage, primary tumor volume, and presence of lymph node
      metastases in cervical cancer patients referred for radiotherapy.
AB  - The aims of this study were to determine, firstly, the relationship between FIGO
      stage and various tumor parameters determined by magnetic resonance imaging
      (MRI), and, secondly, whether any of these parameters were predictors of lymph
      node metastases as determined by fluorine-18 fluorodeoxyglucose positron emission
      tomography (FDG PET) in cervical cancer patients referred for radiotherapy. In 70
      consecutive patients, both PET and MRI visualized all primary tumors except for
      one previously removed by cone biopsy. While clinical diameter and MRI-derived
      diameter showed a significant relationship between these two measurements (r =
      0.70; P < 0.001) there was a large variability in MRI diameter for each FIGO
      stage and wide overlap. The average volume of primary cervical tumor on MRI was
      60 cc (5-256). In FIGO stages, I, II, III and IV, uterine body involvement was
      present in 58%, 73%, 88%, and 100% of 19, 30, 16, and 5 patients, respectively
      (Ptrend= 0.015). Node positivity on FDG PET was present in 11% of patients
      without uterine body extension, but increased to 75% in those with uterine
      involvement. Average tumor volume in node-negative patients was 49 cc (5-186).
      Average tumor volume in node-positive patients was 69 cc (8-256). There was a
      significant association between nodal involvement and both FIGO stage (P = 0.018)
      and uterine body involvement (P < 0.001), but tumor volume and longitudinal MRI
      diameter were not statistically significant in unifactor predictors of nodal
      involvement. In multivariate analysis only uterine body extension, however, was
      independently related to the risk of nodal involvement. In conclusion, MRI
      provides noninvasive tumor size evaluation and can also demonstrate invasion of
      the uterine body that appears to be associated with an increased risk of nodal
      metastasis. This may provide clinically important prognostic information not
      available from current FIGO staging.

PMID- 14675352
TI  - FIGO stage IIIC endometrial carcinoma: resection of macroscopic nodal disease and
      other determinants of survival.
AB  - The objective of this study was to evaluate the potential survival benefit of
      debulking macroscopic adenopathy and other clinical prognostic factors among
      patients with node-positive endometrial carcinoma. Demographic, operative,
      pathologic, and follow-up data were abstracted retrospectively for 41 eligible
      patients with FIGO stage IIIC endometrial cancer. Survival curves were generated
      using the Kaplan-Meier method and statistical comparisons were performed using
      the log rank test, logistic regression analysis, and the Cox proportional hazards
      regression model. All patients had positive pelvic lymph nodes and 20 patients
      (48.8%) had positive para-aortic lymph nodes. Postoperatively, all patients
      received whole pelvic radiation therapy, 17 received extended-field radiation
      therapy, and 15 patients received chemotherapy. The median disease-specific
      survival (DSS) time for all patients was 30.6 months (median follow-up 34. 0
      months). Patients with completely resected macroscopic lymphadenopathy had a
      significantly longer median DSS time (37.5 months), compared to patients left
      with gross residual nodal disease (8.8 months, P = 0.006). On multivariate
      analysis, independent predictors of DSS were gross residual nodal disease (HR
      7.96, 95% CI 2.54-24.97, P < 0. 001), age > or = 65 years (HR 6.22, 95% CI 2.05
      18.87, P = 0.001), and the administration of adjuvant chemotherapy (HR 0.22, 95%
      CI 0.07-0.76, P = 0.016). We conclude that in patients with stage IIIC
      endometrial carcinoma, complete resection of macroscopic nodal disease and the
      administration of adjuvant chemotherapy, in addition to directed radiation
      therapy, are associated with improved survival.

PMID- 14675353
TI  - MDR1 gene expression in endometrial carcinoma.
AB  - The objective of the present study was to determine the MDR1 gene expression in
      endometrial cancer. Twenty-six newly diagnosed patients with endometrial
      carcinoma were included in this study. Patients were treated with surgery
      followed by adjuvant radiotherapy. Four- to six-micrometer sections of the
      archival paraffin-embedded blocks were cut, deparaffinized, and stained by
      immunohistochemical technique using P-glycoprotein dye. Endothelial cell staining
      was used as the positive control of the dye. Immunostaining was categorized from
      0% to 100% based on the percentage of cells stained by examining 3-4 high-power
      fields. The mean P-glycoprotein immunoreactivity for the whole study group was 17
      +/- 25% (0-90). Tauhe mean P-glycoprotein immunoreactivity was 21 +/- 26% (0-90)
      for the endometrioid histology and 6 +/- 13% (0-30) for the clear cell histology.
      P-glycoprotein immunoreactivity was not detected in a case of mucinous histologic
      subtype. There was a significant negative correlation between age and P
      glycoprotein immunoreactivity (r = -0.530, P = 0.005). The P-glycoprotein
      immunoreactivity was found to be 30% positive in only one case of clear cell
      histologic type out of five. However, P-glycoprotein immunoreactivity was not
      significantly lower in clear cell histologic subtype compared with endometrioid
      subtype of endometrial cancer (P = 0.116). P-glycoprotein immunoreactivity was
      found to be 0% in grade 1 (n = 2), 22 +/- 28% in grade 2 (n = 17), and 8 +/- 14%
      in grade 3 (n = 7) patients (P = 0.273). Premenopausal patients were found to
      have a significantly higher P-glycoprotein expression (40 +/- 33)% vs. 11 +/-
      20%, P = 0.04). P-glycoprotein immunoreactivity was found to be less with
      advanced age in endometrial carcinoma. However, premenopausal patients were found
      to have a significantly higher P-glycoprotein expression.

PMID- 14675354
TI  - Synchronous primary endometrial and ovarian cancer with three different
      histologic patterns: A case report.
AB  - Synchronous cancers involving both endometrium and ovary in the female genital
      tract is a well-recognized phenomenon. However, most of them are metastatic
      lesions arising from one organ and simultaneous primary cancer occurring in both
      organs is relatively rare. We report a case with dual primary cancer occurring in
      both ovaries and endometrium with three different histologies. Recently, a 46
      year-old women presented with vaginal bleeding was found to have FIGO stage IC
      clear cell carcinoma of the left ovary, stage IA borderline mucinous cystadoma of
      the right ovary, and stage IB endometrial carcinoma of endometrioid type. We
      present this case with a brief review of references.

PMID- 14675355
TI  - Effective weekly docetaxel for recurrent ovarian cancer: A case report.
AB  - We experienced a case of recurrent ovarian cancer that responded to weekly
      docetaxel. The patient had stage IIIC ovarian cancer (poorly differentiated
      serous adenocarcinoma). After initial remission was achieved by chemotherapy with
      paclitaxel and carboplatin plus cytoreductive surgery, the disease recurred and
      irinotecan therapy achieved temporary remission. During maintenance therapy with
      oral etoposide, the disease recurred again. We then tried five courses of weekly
      docetaxel therapy and it successfully controlled the disease. The progression
      free survival time on weekly docetaxel treatment is now 7 months and the toxicity
      was extremely low. This patient demonstrates the effectiveness of weekly
      docetaxel as salvage chemotherapy for recurrent ovarian cancer.

PMID- 14675357
TI  - High-grade endometrial stromal sarcoma after treatment with tamoxifen in a
      patient treated for breast cancer.
AB  - Tamoxifen has been widely used in breast cancer treatment. In recent years, the
      occurrence of uterine malignancies in patients receiving long-term tamoxifen
      therapy has attracted attention. Most of these malignancies are endometrial
      adenocarcinomas, but low-grade endometrial stromal sarcomas have occasionally
      been reported. Here we report a woman who developed a high-grade endometrial
      stromal sarcoma after receiving postmastectomy tamoxifen therapy. The patient
      underwent a left mastectomy at age 45 and subsequently received oral tamoxifen
      for 3 years. At age 51, she was diagnosed with endometrial stromal sarcoma, for
      which a radical hysterectomy was performed. High-grade endometrial stromal
      sarcoma was diagnosed by postoperative histologic examination. Immunostaining for
      the estrogen receptor was negative in sarcoma cells, but positive in the residual
      endometrial epithelium and the nucleus of adjacent stromal cells within the
      tumor. The patient has now survived disease-free for 37 months after surgery.

PMID- 14675356
TI  - Coincidental detection of T-cell rich B cell lymphoma in the para-aortic lymph
      nodes of a woman undergoing lymph node dissection for cervical cancer: a case
      report.
AB  - The diagnosis of cervical squamous cell carcinoma with concurrent T-cell rich B
      cell lymphoma in dissected lymph nodes has not been reported to our knowledge. In
      our case, the biopsy of an exophytic lesion at the uterine cervix showed squamous
      cell carcinoma in a 50-year-old woman presenting with postcoital bleeding. Type
      III hysterectomy, bilateral salpingo-oophorectemy, bilateral pelvic, para-aortic
      lymph node dissections were performed. Pathologic examination revealed a T-cell
      rich B cell lymphoma in some lymph nodes beside squamous cell carcinoma in
      several of others. ELISA for human immuno-deficiency virus (HIV) was negative.
      The cervical carcinoma was staged as FIGO clinical stage IB1 and the lymphoma as
      Ann Arbor IIA. Six cycles of CHOP (cyclophosphamide, adriamycin, vincristine, and
      prednisolon) chemotherapy for the lymphoma and concomitant pelvic
      chemoradiotherapy with cisplatin for cervical cancer were given. In this rare
      coincidence, the best available therapy for each of the diseases should be
      considered individually. We also suggest that HIV screennig test be carried out,
      because both diseases may be related to human immuno-deficiency virus, although
      our patient is HIV-negative.

PMID- 14675358
TI  - Longitudinal CA125 detection of sporadic papillary serous carcinoma of the
      peritoneum.
AB  - In this case, rising longitudinal levels of CA125 were significant in the
      detection of peritoneal papillary serous carcinoma, and led to the indication for
      surgery. Rising longitudinal CA125 has been shown to be important in the
      detection of ovarian cancer, but little data exist as to its relevance for the
      detection of peritoneal papillary serous carcinoma. This rare primary tumor is
      usually associated with women at high risk for epithelial ovarian carcinoma,
      although this patient was not at high risk as she had no familial breast or
      ovarian cancer history.

PMID- 14675359
TI  - [Uterine carcinosarcoma related to tamoxifen].

PMID- 14675361
TI  - Health information needs of visually impaired people: a systematic review of the
      literature.
AB  - Access to, and provision of, information is key to reducing health inequalities
      in health and social care. However, information is not always accessible and does
      not always meet the needs of specific groups. One such group is people who are
      visually impaired. The aim of the present study was to identify the health
      information needs of visually impaired people, and highlight major gaps in the
      literature. A systematic review of the literature was undertaken following, where
      possible, the NHS Centre for Reviews and Dissemination framework. Modifications
      included the sources searched, the critical appraisal checklist used (Critical
      Skills Training in Appraisal for Librarians) and the method of data synthesis.
      Out of the 1114 references identified, only 16 met the inclusion criteria.
      Quality of reporting of the literature was poor, and this must be taken into
      consideration when interpreting the findings of this review. The majority of
      studies were concerned with information for healthy living (e.g. health
      promotion). The focus of the remaining studies was on information about visual
      impairment or coping with visual impairment, and about accessing health services
      (e.g. medication labels and appointment letters). The majority of studies
      conducted to date have concentrated on the format of information. There are
      surprisingly few empirical studies which have examined the health information
      needs of this group. A number of gaps in the literature have been identified.
      These relate to the types of health information, non-format aspects of
      information (e.g. content and timing), sources of health and social care
      information, treating visually impaired people as a heterogeneous group, and
      recognising the value of actively involving visually impaired people in the
      research process. Although this review has identified a number of implications
      for practice, the paucity of evidence places a heavier onus on future research.
      Visually impaired people are likely to have unique health and social care
      information needs which are worthy of exploration in their own right.

PMID- 14675362
TI  - The Golden Freeway: a preliminary evaluation of a pilot study advancing
      information technology as a social intervention for boys with Duchenne muscular
      dystrophy and their families.
AB  - Established information technology was used in an attempt to reduce social
      isolation by providing each family who had a child with Duchenne muscular
      dystrophy with a personal computer, and e-mail and Internet connectivity. Seventy
      four of the 88 families in the north of England (i.e. Cumbria, Durham,
      Northumberland, Teesside, and Tyne and Wear) with a boy with Duchenne muscular
      dystrophy who was diagnosed before January 2000 had the equipment installed.
      Evaluations of equipment usage and parental perceptions of the project were
      carried out at 3 and 12 months post-installation. Results from quantitative and
      qualitative interviews with parents indicated that benefits accrued to the
      families and to the boys themselves: family relationships can be extended, and
      the boys can acquire a degree of independence which, according to parents' views,
      can boost self-confidence and self-esteem. As hoped, social isolation was felt to
      have been reduced, and an occupation, interest and enjoyment provided. The
      greatest use of the computer was for schoolwork with siblings sharing in this.
      Cost proved to be a problem for a number of families. For the project team, there
      were unexpected aspects: creating an e-community was more difficult than
      anticipated, more training was required and not all families would ever use the
      equipment to its fullest. However, families did emphasise the value of the
      project as a way of opening the world for their sons.

PMID- 14675363
TI  - Exploring the experiences of partners who live with a chronic low back pain
      sufferer.
AB  - Chronic low back pain (CLBP) is a condition that causes individuals considerable
      distress. It also presents a significant challenge to the health service and is
      often viewed by clinicians as frustrating to manage. The purpose of the present
      paper is to explore the experiences of individuals in the immediate social sphere
      of those suffering from CLBP and their role in care-giving for their partner. An
      approach was taken using two qualitative research methods to gather data:
      journals and focus groups. Findings from the journals and the focus groups
      revealed issues for partners of CLBP sufferers in relation to living with their
      partners' pain, perceptions of healthcare and the dominance of illness over
      social contacts. Key themes revealed the complex emotions experienced by
      respondents, and underlined the need for their role as care givers and partners
      to be acknowledged by healthcare professionals. The data also highlighted
      respondents' desire to have greater involvement in their partners' healthcare,
      which includes provision of relevant information and involvement with therapeutic
      interventions. The findings emphasise the need for healthcare professionals to
      include and acknowledge partners and others in the immediate social sphere of
      patients in the management of chronic conditions.

PMID- 14675364
TI  - Carer satisfaction with end-of-life care in Powys, Wales: a cross-sectional
      survey.
AB  - A cross-sectional postal survey of bereaved carers was conducted in order to
      examine levels of satisfaction with services provided for people in their last
      year of life in the rural county of Powys, Wales, UK. A self-complete
      questionnaire, using a modified version of the Views of Informal Carers -
      Evaluation of Services instrument was sent to all bereaved carers of all those
      people dying of cancer in Powys between 1 April 1999 and 30 June 2001. Eight
      hundred and five (out of a possible of 815 people) were contacted and 407 agreed
      to receive the questionnaire. Out of these 407 individuals, 301 (74% of those who
      agreed to receive a questionnaire and 37% of the 815 contacted) returned a
      completed questionnaire. A single reminder letter was sent to non-responders. It
      was found that the majority of those who received help from district nurses or
      practice nurses (90%) said that they were excellent or good. However, nearly 40%
      of respondents reported needing more nursing help. More help was also needed from
      social care services. For 103 out of the 301 respondents, it was known that the
      deceased person wanted to die at home; only 44 did so. Only one-fifth of
      respondents had the opportunity to talk to someone from health and social
      services after their bereavement; a large majority (four-fifths) found this
      helpful. One-tenth of respondents reported untreated pain at home; however, there
      was evidence for an increasing proportion of those treated having received good
      pain relief. Although there are high levels of satisfaction with care and
      services received by Powys residents, deficits exist in relation to: symptom
      control, nursing help, assistance from social services with transport and
      bathing, communication, and bereavement support.

PMID- 14675365
TI  - Factors associated with variations in older people's use of community-based
      continence services.
AB  - Many people who have urinary incontinence and who may benefit from healthcare and
      professional advice do not currently access UK National Health Service services,
      even though effective treatments are available in the community. Older people
      have an increased prevalence of incontinence and a correspondingly increased need
      for continence services. Therefore, increasing older people's access to
      continence services has the potential to reduce inequalities and improve quality
      of life. The present study aimed to identify older people with urinary
      incontinence living in the community, to describe and compare the characteristics
      of users and non-users of continence services, and to identify factors which
      prevent older people seeking help. A cross-sectional postal survey of patients
      aged over 65 years registered with four general practices in an urban area found
      an overall prevalence of 39% of older people with urinary incontinence, only 15%
      of whom had accessed services. Two-thirds of respondents who reported that they
      experienced urinary leakage several times per week to all the time, and up to two
      thirds of those reporting leakage of moderate or large volumes of leakage had not
      accessed services. The majority of older people are in regular contact with
      health professionals, and the greatest single influence on use of services was
      that of being asked whether there were continence problems by a health
      professional. Being married or having a partner, experiencing less pain
      generally, and suffering relatively high frequency and volumes of urinary leakage
      also appeared to be associated independently with continence service use. In
      conclusion, there appears to be considerable unmet need for continence services.
      Health professionals should be aware that incontinence is an important health
      problem for older people, and by asking older people specifically about urinary
      leakage, they could reduce inequalities in use of services.

PMID- 14675366
TI  - Can a health advocate for homeless families reduce workload for the primary
      healthcare team? A controlled trial.
AB  - The objective of the present study was to determine whether provision of health
      advocacy for homeless patients would reduce the burden of care for a primary
      healthcare team. The impact of a health advocacy intervention was assessed in a
      quasi-experimental, three-armed controlled trial. Homeless patients registering
      at an inner-city health centre were allocated in alternating periods to health
      advocacy (with or without outreach registration) or 'usual care' over a total
      intake period of 3 years. The client group were homeless people in hostels or
      other temporary accommodation in the Liverpool 8 area of the UK. The majority of
      participants (n = 400) were women (76%) in their twenties (mean age = 26.6
      years). Most (63%) were temporarily housed at either one of the women's refuges
      or Liverpool City Council family hostels, and all were registered with an inner
      city health centre. Data on health service utilisation over a 3-month period was
      collected for all clients recruited to the study and direct health service costs
      were measured. Homeless adults who were proactively registered by the health
      advocate on outreach visits to hostels made significantly less use of health
      centre resources whilst having more contact with the health advocate than
      patients who registered at the health centre at a time of need. There was no
      reduction in health centre workload when the offer of health advocacy was made
      after registration at the health centre. The additional costs of providing health
      advocacy were offset by a reduction in demand for health-centre-based care. The
      results demonstrate that health advocacy can alter the pattern of help-seeking by
      temporarily homeless adults. The intervention was cost-neutral. The short-term
      health service workload associated with symptomatic homeless patients requiring
      medication was not reduced, but outreach health advocacy was used successfully to
      address psycho-social issues and reduce the workload for primary care staff.

PMID- 14675367
TI  - Collaboration and local networks for rural and remote primary mental healthcare
      in South Australia.
AB  - This paper draws on a consultation with 200 stakeholders about a mental health
      plan in the most remote region of South Australia to discuss primary mental
      healthcare improvement strategies. In rural and remote environments, a lack of
      services means that it is more difficult to deal with a mental illness or provide
      assistance for circumstantial life problems. The authors' consultations revealed
      difficulties with service access, acceptability and teamwork. They also found
      that the availability of local human service workers leads to their use as first
      level mental health contacts, but these workers are neither skilled nor supported
      for this. These difficulties will require attention to the boundaries between
      different service providers which can otherwise create inflexibility and service
      gaps. The regional mental health plan that is being rolled out will develop
      collaboration through regional interagency task groups, networking groups for
      local human service workers and the position of a regional mental health
      coordinator in order to overcome these difficulties and to operationalise service
      partnerships.

PMID- 14675368
TI  - Keratin 9 gene mutations in five Korean families with epidermolytic palmoplantar
      keratoderma.
AB  - Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant disease
      characterized clinically by localized palmoplantar thickening and
      histopathologically by granular degeneration of the epidermis. Recent molecular
      biological studies have revealed that EPPK is caused by mutations of the keratin
      9 gene in sequences mainly encoding the highly conserved 1 A rod domain. Here we
      demonstrate a novel mutation of N160H (position 8 of the 1 A domain) and two
      other previously reported mutations, R162W and N160S, in five unrelated Korean
      families with EPPK. The three-dimensional structure of the 1 A domain of the
      related vimentin intermediate filament protein chain is now known. Based on its
      likely similarity to the keratin 9 chain, we predict that inappropriate amino
      acid substitutions in position 10 of 1 A will likely interfere with coiled-coil
      dimer stability, and those in position 8 will interfere with tetramer stability.
      Accordingly, these mutations compromise the structural integrity of the keratin
      intermediate filaments leading to the pathology of EPPK.

PMID- 14675390
TI  - Immunogenetics of a new HLA-B null allele, HLA-B*4423N.
AB  - The second example of an HLA-B*44 null allele (B*4423N) was identified by
      discrepancies between serological and polymerase chain reaction-sequence-specific
      primer (PCR-SSP) typing in two north-western European Caucasoid unrelated stem
      cell donor volunteers. HLA-B*4423N was identical to B*440201 except for a single
      nucleotide substitution at position 493 in exon 3, resulting in a premature stop
      codon at bases 493-495 (TAG rather than CAG at codon 141). As expected,
      comprehensive serological testing using 54 antisera, directed towards B44 or Bw4,
      failed to identify the HLA-B44 (Bw4) specificity. The B*4423N-bearing haplotype
      was identified as A*0201, Cw*0501, DRB1*0408, DRB4*01, DQA1*03, DQB1*0304 and the
      frequency of B*4423N estimated as 0.00006 (carriage frequency 0.0121%) in 16 533
      subjects resident in Wales.

PMID- 14675392
TI  - Two novel somatic mutations in the human interleukin 6 promoter region in a
      patient with sporadic breast cancer.
AB  - Two new single nucleotide mutations were observed within the promoter region of
      human interleukin-6 gene (IL-6) in the tumour sample of a patient with sporadic
      breast cancer, which was a somatic change. Both mutations, one at -125 (C > G)
      and the other at position -173 (G > T) from the translation start site, were
      transversions observed at new positions, not reported earlier. In addition to
      these two novel mutations in this patient, a known somatic polymorphism was also
      observed at position -174 (G > C) (from the transcription initiation site,
      redesignated as -236 from the translational initiation site as per the HUGO
      nomenclature). Further, a preliminary comparative analysis of the studied
      promoter region by the 'ConsInspector 3.0' program, where the mutated sequence
      (AF362378) was compared with the sequence existing in the database (Y00081),
      depicted the presence of the variations in putative binding sites for
      transcription factors such as glucocorticoid response element (GRE) and nuclear
      factor kappa-B (NFkappa-B), which could lead to differential expression of this
      gene.

PMID- 14675393
TI  - HLA in Czech adult patients with autoimmune diabetes mellitus: comparison with
      Czech children with type 1 diabetes and patients with type 2 diabetes.
AB  - Type 1 diabetes results from an autoimmune insulitis, associated with HLA class
      II alleles. The evidence about HLA allele association is not clear in patients
      diagnosed after 35 years of age. In this study we have analyzed HLA alleles of
      DQB1 and DRB1 genes by sequence specific primer (SSP)-PCR technique in adult
      patients with disease onset after 35 years of age. Two hundred and eighty-one
      patients were divided into three groups according to the insulin therapy, the
      level of C peptide (CP), and GAD antibodies (anti-GAD). Group 1 (type 1 diabetes
      in adults) was characterized by CP less than 200 pmol/L and anti-GAD more or less
      than 50 ng/mL (n = 80). All of them had insulin therapy within 6 months after
      diagnosis. Group 2 latent autoimmune diabetes mellitus in adults (LADA) was
      defined by a minimum 6-month-long phase after diagnosis without insulin therapy,
      and was characterized by CP more than 200 pmol/L and anti-GAD more than 50 ng/mL
      (n = 70). Group 3 (type 2 diabetes) was characterized by CP more than 200 pmol/L
      and anti-GAD less than 50 ng/mL (n = 131). None ever had insulin therapy. In
      group 1, there was increased frequency of DRB1*04 (45.0% vs. controls 14.1%, OR =
      5.0, P < 0.0005) and DQB1*0302 alleles (43.3% vs. controls 11.1%, OR = 6.1, P <
      0.00005). There was increased frequency of DRB1*03 and DQB1*0201, and decreased
      frequency of DQB1*0602 (3.3% vs. controls 20.2%), but it was not significant. In
      group 2, there was a significantly increased frequency of DRB1*03 only (50.0% vs.
      controls 21.2%, OR = 3.7, P < 0.05). Compared with children with type 1 diabetes
      and adults with type 2 diabetes (group 3), we conclude that the presence of
      predisposing DQB1 alleles in adults with type 1 diabetes decreases with the age,
      probably due to environmental factors. Only the DRB1*03, but not the DQB1 gene,
      becomes the main predisposing allele in LADA patients. These findings suggest
      that the presence of HLA-DQB1*0302 identifies patients at high risk of requiring
      insulin treatment. Type 1 diabetes mellitus (DM) in children or adults may have
      partly different immunogenetic etiopathogenesis than LADA.

PMID- 14675394
TI  - Cytokine gene single nucleotide polymorphisms and susceptibility to and prognosis
      in cutaneous malignant melanoma.
AB  - Cutaneous malignant melanoma (CMM) is a potentially fatal malignancy in which
      exposure to UV light is the most important risk factor. Several lines of evidence
      suggest that CMM patients develop an immune response to their tumours, although,
      in most cases, anti-tumour immune responses are insufficient to abrogate tumour
      development. Polymorphism in genes regulating the immune response and cell growth
      may result in increased susceptibility to and/or poorer prognosis in certain
      individuals. In this study, we addressed whether single nucleotide polymorphisms
      (SNPs) associated with differential expression of selected pro- and anti
      inflammatory cytokines and growth factors [interleukin (IL)-1beta-35 and -511, IL
      2 -330, IL-4 -590, IL-6 -174, IL-8 -251, interferon (IFN)-gamma+874 and
      transforming growth factor (TGF)beta1 +915] or as markers of candidate cytokine
      genes (IL-12 +1188) are associated with susceptibility to or known prognostic
      indicators (e.g. initial tumour growth phase, Breslow thickness, mitotic count in
      vertical growth phase tumours, tumour regression) in CMM. One hundred and sixty
      nine British caucasian CMM patients and 261 controls were included in the study
      and all SNPs were genotyped by ARMS-PCR. No SNP genotypes or alleles showed
      significant associations with CMM susceptibility and only the IL-1beta-511 TT
      genotype was associated with thinner invasive tumours at presentation, as
      assessed by Breslow thickness at the clinically significant cut-off point of 1.5
      mm [occurring in 2/51 (3.9%) thicker vs. 14/78 (17.9%) thinner tumours (P = 0.03;
      relative risk = 0.29 (95% confidence interval 0.05-0.95)]. These findings suggest
      that - with the possible exception of IL-1beta- genetic variation associated with
      differential expression of the selected pro- and anti-inflammatory cytokines is
      unlikely to play a major role in susceptibility to and prognosis in CMM.

PMID- 14675395
TI  - Human platelet alloantigens (HPAs): PCR-SSP genotyping of a UK population for 15
      HPA alleles.
AB  - Alloimmunization to human platelet alloantigens (HPAs) is responsible for
      neonatal alloimmune thrombocytopenia (NAIT), post-transfusional purpura (PTP) and
      platelet transfusion refractoriness. HPAs may also have a role as
      histocompatibility antigens in transplantation as well as associations with
      cardiac disease. We have developed a polymerase chain reaction-sequence-specific
      primer (PCR-SSP) assay capable of detecting 15 HPA allelic variants. As part of
      the validation of the assay, 134 UK renal donors were genotyped to determine HPA
      allele frequencies in the UK population. The HPA allele frequencies obtained are
      consistent with those of the other European studies: GP1A*1 (HPA-5a) and GP1A*2
      (HPA-5b), 0.914 and 0.086, respectively; GP1BA*1 (HPA-2a) and GP1BA*2 (HPA-2b),
      0.925 and 0.075; GP2B*1 (HPA-3a) and GP2B*2 (HPA-3b), 0.627 and 0.373; GP3A*1
      (HPA-1a) and GP3A*2 (HPA-1b), 0.840 and 0.161. The rare alleles GP2B*3 (HPA-9bw)
      and GP3A*3 to *8 (HPA-4b, -6b, -7bw, -8bw, -10bw and -11bw, respectively) were
      all absent. This comprehensive HPA genotyping assay allows rapid, accurate and
      reproducible results at low cost.

PMID- 14675397
TI  - Coeliac disease: investigation of proposed causal variants in the CTLA4 gene
      region.
AB  - Coeliac disease (CD) is an immune-mediated enteropathy triggered by gluten in
      genetically predisposed individuals. Patients with CD have an increased
      prevalence of other autoimmune disorders, including type 1 diabetes (T1D) and
      Graves' disease (GD). CD shares with these conditions certain HLA susceptibility
      alleles. A number of studies have also shown association of autoimmune diseases,
      including CD, with the CD28-cytotoxic T lymphocyte antigen 4 (CTLA4)-inducible
      costimulator (ICOS) region of chromosome 2q33, but until recently the precise
      causal variant has remained unknown. Recently, it was shown that, in GD, CT60
      (+6230G>A), a single nucleotide polymorphism (SNP) at the end of the CTLA4
      transcript, is associated with an alteration in the ratio of splice forms of the
      CTLA4 gene and that this ratio affects disease susceptibility. A similar but
      weaker association was found with T1D. There is also an independent association
      of GD and T1D with the SNP MH30 (-23 327G>C), which possibly affects promoter
      region function. Hypothesizing that CT60 and MH30 may be causal variants in other
      autoimmune disorders, we investigated these SNPs in CD using 149 family trios and
      100 unrelated/unaffected controls. No association was detected with either SNP
      using both the transmission disequilibrium test (TDT) and case-control methods.
      Our study appears to have good power to detect moderate genetic effects, but
      possibly these SNPs exert too weak an effect on risk of CD to have been detected
      in our sample. Alternatively, the previously noted association of CD with the
      CTLA4 gene region may be due to different causal variants. Unlike T1D and GD, CD
      is not a true autoimmune disease, and CD has different associations at the CTLA4
      exon 1 SNP +49G>A from all other autoimmune disorders. MH30, CT60, and other SNPs
      in the region may still warrant further investigation in other CD samples.

PMID- 14675396
TI  - IL12B and IRF1 gene polymorphisms and susceptibility to celiac disease.
AB  - Celiac disease (CD) is a common gastro-intestinal disorder resulting from
      permanent intolerance to wheat gliadins and related proteins in rye and barley.
      In addition to the strong genetic association with HLA-DQ2 and HLA-DQ8, a genetic
      region on chromosomes 5 (CELIAC2) has been identified that harbours a
      susceptibility gene for CD. The gene(s) responsible for this association,
      however, remains to be identified. In the present study we evaluated
      polymorphisms in the genes encoding interleukin-12 p40 (IL12B) and interferon
      regulatory factor 1 (IRF1). Both genes are located in the celiac2 region, and
      have key roles in inducing interferon (IFN)-gamma secreting T helper 1 (Th1)
      cells, one of the immunological hallmarks of CD. The frequencies of a TaqI gene
      polymorphism in the 3' UTR of IL12B and a HinfI gene polymorphism in the 3' UTR
      of IRF1 were studied in 258 Dutch CD patients and 237 ethnically matched healthy
      controls. The transmission of the polymorphic variants from parents to affected
      child was determined in 123 families with at least one affected child. The
      frequencies of the IL12B TaqI gene polymorphism and the IRF1 HinfI gene
      polymorphism did not differ significantly between patients and controls. In
      addition, in the family study, no deviation from the expected transmission from
      parents to affected child of any of the polymorphic variants was found. The IL12B
      TaqI and the IRF1 HinfI gene polymorphisms do not appear to be involved in
      susceptibility to CD. Further studies on the factors that drive the Th1
      immunopathology in CD are required.

PMID- 14675391
TI  - Novel classical MHC class I alleles identified in horses by sequencing clones of
      reverse transcription-PCR products.
AB  - Improved typing of horse classical MHC class I is required to more accurately
      define these molecules and to extend the number identified further than current
      serological assays. Defining classical MHC class I alleleic polymorphism is
      important in evaluating cytotoxic T lymphocyte (CTL) responses in horses. In this
      study, horse classical MHC class I genes were analyzed based on reverse
      transcription (RT)-PCR amplification of sequences encoding the polymorphic
      peptide binding region and the more conserved alpha 3, transmembrane and
      cytoplasmic regions followed by cloning and sequencing. Primer sets included a
      horse classical MHC class I-specific reverse primer and a forward primer
      conserved in all known horse MHC class I genes. Sequencing at least 25 clones
      containing MHC class I sequences from each of 13 horses identified 25 novel
      sequences and three others which had been described. Of these, nine alleles were
      identified from different horses or different RT-PCR and 19 putative alleles were
      identified in multiple clones from the same RT-PCR. The primer pairs did not
      amplify putative non-classical MHC class I genes as only classical MHC class I
      and related pseudogenes were found in 462 clones. This method also identified
      classical MHC class I alleles shared between horses by descent, and defined
      differences in alleles between horses varying in equine leukocyte antigen (ELA)-A
      haplotype as determined by serology. However, horses sharing ELA-A haplotypes
      defined by serotyping did not always share cDNA sequences, suggesting
      subhaplotypic variations within serologically defined ELA-A haplotypes. The 13
      horses in this study had two to five classical MHC class I sequences, indicating
      that multiple loci code for these genes. Sequencing clones from RT-PCR with
      classical MHC class I-specific primers should be useful for selection of
      haplotype matched and mismatched horses for CTL studies, and provides sequence
      information needed to develop easier and more discriminating typing procedures.

PMID- 14675398
TI  - Polymorphisms of the interferon gamma and interleukin 10 genes in human
      brucellosis.
AB  - We genotyped 83 patients with brucellosis and 101 controls to determine the
      influence of polymorphisms of the interferon gamma (IFNG) and interleukin 10
      (IL10) genes on protection against, or susceptibility to, human brucellosis and
      its complications. The results showed a significant increase in the IFNG +874A/A
      genotype in patients compared with controls (34% vs. 19%) (P = 0.023, odds ratio
      = 2.17, 95% confidence interval 1.05-4.51). No significant differences were
      detected in the frequency distribution of the IL10 genotypes between patients and
      controls. Similarly, no significant differences were observed in the genotype
      frequencies of either of the two cytokines between complicated and non
      complicated forms of brucellosis. Persons who are homozygous for the IFNG +874A
      allele may have a higher risk of contracting brucellosis.

PMID- 14675399
TI  - Nomenclature for factors of the HLA system, update September 2003.

PMID- 14675400
TI  - Isolated 12th cranial nerve palsy as a complication of multiple myeloma.

PMID- 14675401
TI  - Plumbism.

PMID- 14675402
TI  - Abnormal osteoclasts and bone marrow fibrosis in Paget's disease of the bone.

PMID- 14675403
TI  - Modern management of children with haemophagocytic lymphohistiocytosis.

PMID- 14675404
TI  - The diagnosis of deep vein thrombosis in symptomatic outpatients and the
      potential for clinical assessment and D-dimer assays to reduce the need for
      diagnostic imaging.

PMID- 14675405
TI  - Fludarabine, cytosine arabinoside, granulocyte-colony stimulating factor with or
      without idarubicin in the treatment of high risk acute leukaemia or
      myelodysplastic syndromes.
AB  - The combination of fludarabine (FDR), high dose cytarabine and granulocyte colony
      stimulating factor (FLAG) with or without idarubicin (Ida) was used in the
      treatment of poor risk acute leukaemia or myelodysplastic syndrome (MDS) in a
      single centre experience. A total of 105 patients were treated over a 4-year
      period with 59% achieving a complete remission (CR); no statistical difference
      observed between FLAG and FLAG-Ida. For patients responding to FLAG +/- Ida, the
      median event-free survival (EFS) was 11 months and 23% at 5 years. Such patients
      proceeded either to further chemotherapy or a haematopoietic stem cell transplant
      (HSCT). The median EFS (13 months vs. 8 months) and projected 5-year survival
      (37% vs. 13%) of patients undergoing HSCT was significantly better than those who
      did not (P = 0.021). In all, 14 of 72 patients remain alive in continuing CR
      (median duration 43 months) with 10 of 31 having had a HSCT vs. four of 41 that
      did not (P = 0.033). Both regimens were well tolerated, with the majority of
      patients experiencing grade 1 or less non-haematological toxicity (mainly nausea
      and vomiting). The median time to neutrophil and platelet recovery was 28 and 31
      d, respectively. No significant differences were seen with the addition of ida.
      There was a 17% incidence of treatment-related deaths, of which 39% was caused by
      invasive aspergillus infection. The results show that FLAG +/- Ida is an
      effective and well-tolerated remission induction regimen for poor risk leukaemia
      and MDS.

PMID- 14675406
TI  - Successful treatment without cranial radiotherapy of children receiving
      intensified chemotherapy for acute lymphoblastic leukaemia: results of the risk
      stratified randomized central nervous system treatment trial MRC UKALL XI (ISRC
      TN 16757172).
AB  - Concern about late adverse effects of cranial radiotherapy (XRT) has led to
      alternative approaches to eliminate leukaemia from the central nervous system
      (CNS) in childhood acute lymphoblastic leukaemia (ALL). The Medical Research
      Council UKALL XI trial recruited 2090 children with ALL between 1990 and 1997.
      Median follow-up is 7 years 9 months; event-free survival (EFS) and overall
      survival were 63.1% and 84.6%, respectively, at 5 years and 59.8% and 79.4% at 10
      years. The isolated CNS relapse rate was 7.0% at 10 years. Patients were
      randomized for CNS-directed therapy within white blood cell (WBC) groups. For WBC
      <50 x 10(9)/l, high-dose intravenous methotrexate (HDMTX) (6-8 g/m2) with
      intrathecal methotrexate (ITMTX) was compared with ITMTX alone, and was
      significantly better at preventing isolated and combined CNS relapse, but non-CNS
      relapses were similar. There was no significant difference in EFS at 10 years,
      64.1% [95% confidence interval (CI) 60.4-67.8] with HDMTX plus ITMTX, and 63.0%
      (95% CI 59.5-66.5) with ITMTX alone. For WBC >/=50 x 10(9)/l, HDMTX with ITMTX
      was compared with XRT and a short course of ITMTX. CNS relapses were
      significantly fewer with XRT, but there was a non-significant increase in non-CNS
      relapses. EFS was not significantly different, being 55.2% (95% CI 47.8-62.6) at
      10 years with XRT and 52.1% (95% CI 44.8-59.4) with HDMTX plus ITMTX.

PMID- 14675407
TI  - Asymmetric multiplex-polymerase chain reaction - a high throughput method for
      detection and sequencing genomic fusion sites in t(4;11).
AB  - Chromosomal translocations are a characteristic feature of leukaemia and other
      malignant diseases. As clonal markers, they can be applied to identify and
      quantify the number of malignant cells by polymerase chain reaction (PCR)
      methods. The translocation t(4;11) is present in >60% of infant leukaemia. In
      order to facilitate the sequencing of chromosomal breakpoints, we developed an
      optimized set of 30 PCR primers and a new approach, designated as asymmetric
      multiplex PCR (am-PCR). Due to the high number of primers, small breakpoint
      spanning DNA fragments are obtained in one nested multiplex PCR reaction. All PCR
      products contain an identical binding site for the initiation of direct
      sequencing. By using am-PCR, the translocation t(4;11) was examined in bone
      marrow and blood samples from children with acute leukaemia. Compared with
      previously described methods for the determination of genomic breakpoints, am-PCR
      may be advantageous with regard to its simplicity and rapidity. Breakpoint
      spanning sequences were also evaluated with regard to their applicability as
      unique clonal markers to design primers and probes for minimal residual disease
      quantification by real-time PCR. This approach can easily be adapted to other
      chromosomal translocations in malignant diseases for the detection and analysis
      of clone-specific DNA markers.

PMID- 14675408
TI  - FcgammaRIIB is differentially expressed during B cell maturation and in B-cell
      lymphomas.
AB  - FcgammaRIIB, a low affinity receptor for the Fc portion of immunoglobulin G
      (IgG), is thought to drive negative selection of B cells in germinal centers (GC)
      by inducing apoptosis upon interaction with immune complexes. Its expression was
      investigated by immunohistochemistry in 22 reactive lymphoid tissues and 112 B
      cell lymphomas. Pre-GC mantle cells, marginal zone cells and their neoplastic
      counterparts expressed FcgammaRIIB. The B chronic lymphocytic leukaemia (B
      CLL)/small lymphocytic lymphomas were also positive. Not detected in GC,
      FcgammaRIIB was expressed in 52% of follicular lymphomas and in 20% of diffuse
      large B cell lymphomas (DLBCL). In DLBCL, FcgammaRIIB expression was linked to
      transformation (P < 0.001). Re-analysis of a gene profile data set from the
      Lymphochip microarrays showed that FcgammaRIIB expression in the activated B-like
      DLBCL subgroup was higher than in the GC-like one (P < 0.04), and was associated
      with an adverse prognostic both in univariate (P < 0.003) and in multivariate
      analysis including the International Prognostic Indicator (IPI) (P < 0.01). Thus
      these results challenge the potential role of FcgammaRIIB during B-cell selection
      in GC, and suggest a prognostic value of FcgammaRIIB expression in DLBCL.

PMID- 14675409
TI  - Severe pulmonary hypertension: a frequent complication of stem cell
      transplantation for malignant infantile osteopetrosis.
AB  - This report describes eight infants who developed acute severe pulmonary arterial
      hypertension (PAH) at days -2 to +89 after allogeneic stem cell transplantation
      (SCT) for malignant infantile osteopetrosis (MIOP). They were taken from a total
      of 28 children (frequency 29%) transplanted for this disease at three
      institutions between 1996 and 2002. Typical presentations were acute dyspnoea,
      hypoxia and brady/tachycardia usually in the absence of fever, crepitations or
      other evidence of infection. Six patients (75%) required assisted ventilation and
      five (62%) died. There was clinical or pathological evidence of veno-occlusive
      disease (VOD) in three children, but absence of VOD in the remaining five
      suggests that a separate disease process may be responsible for the PAH.
      Responses to nitric oxide (NO), defibrotide (DF), nicardipine and steroids in
      varying combinations were disappointing. Three children showed sustained
      improvement after administration of epoprostenol (EP, prostacyclin) in
      conjunction with NO and/or DF and remain well and free of PAH 25, 31 and 32
      months post-transplant. PAH must therefore be excluded in any child who becomes
      acutely breathless after SCT for osteopetrosis.

PMID- 14675411
TI  - In vitro aspirin resistance detected by PFA-100 closure time: pivotal role of
      plasma von Willebrand factor.
AB  - The in vitro closure time (CT), determined by the Platelet Function Analyzer (PFA
      100), is used to monitor patients treated with aspirin. A relatively high
      percentage of in vitro aspirin resistance was reported despite an adequate
      inhibition of platelet response to arachidonic acid and we investigated whether
      high plasma levels of von Willebrand factor ristocetin cofactor activity
      (vWF:RCo) may contribute to this profile. Platelet aggregation test, CT [collagen
      adrenaline (CEPI-CT) and collagen adenosine 5'-diphosphate (ADP) (CADP-CT)], and
      vWF:RCo levels were evaluated in 55 consecutive patients receiving aspirin (75
      250 mg/d) versus 32 untreated control subjects. All the aspirin-treated patients
      showed platelet aggregation responses that reflected the aspirin intake. However,
      CT data analysis enabled aspirin good-responder (GR) and aspirin bad-responder
      (BR) patients to be identified. All GR group subjects (n = 27), had a CEPI-CT and
      a CADP-CT longer than 300 s and 96 s respectively. The BR group (n = 28) had CEPI
      CT values below 200 s and all CADP-CT were in the normal range (77 +/- 19 s).
      Interestingly, the BR plasma vWF:RCo levels were significantly higher (159 +/-
      43%) than those of the GR group (121 +/- 34%) (P < 0.01), which were similar to
      control values (114 +/- 31%). A negative correlation between vWF:RCo and CT
      values was established. We demonstrate that in vitro aspirin-resistance, revealed
      by PFA-100 CT prolongation failure, is correlated to increased plasmatic vWF:RCo
      levels, reinforcing its particular importance in PFA-100 cartridges performance.

PMID- 14675410
TI  - Transplantation of a combination of CD133+ and CD34+ selected progenitor cells
      from alternative donors.
AB  - Positive selected haematopoietic stem cells are increasingly used for allogeneic
      transplantation with the CD34 antigen employed in most separation techniques.
      However, the recently described pentaspan molecule CD133 appears to be a marker
      of more primitive haematopoietic progenitors. Here we report our experience with
      a new CD133-based selection method in 10 paediatric patients with matched
      unrelated (n = 2) or mismatched-related donors (n = 8). These patients received a
      combination of stem cells (median = 29.3 x 10(6)/kg), selected with either anti
      CD34 or anti-CD133 coated microbeads. The proportion of CD133+ selected cells was
      gradually increased from patient to patient from 10% to 100%. Comparison of
      CD133+ and CD34+ separation procedures revealed similar purity and recovery of
      target populations but a lower depletion of T cells by CD133+ selection (3.7 log
      vs. 4.1 log, P < 0.001). Both separation procedures produced >90% CD34+/CD133+
      double positive target cells. Engraftment occurred in all patients (sustained
      primary, n = 8; after reconditioning, n = 2). No primary acute graft versus host
      disease (GvHD) >/= grade II or chronic GvHD was observed. The patients showed a
      rapid platelet recovery (median time to independence from substitution = 13.5 d),
      whereas T cell regeneration was variable. Five patients are alive with a median
      follow-up of 10 months. Our data demonstrates the feasibility of CD133+ selection
      for transplantation from alternative donors and encourages further trials with
      total CD133+ separated grafts.

PMID- 14675412
TI  - A population based, unselected, consecutive cohort of patients with acquired
      haemophilia A.
AB  - Previous studies in acquired haemophilia A have reported on cohorts of patients
      referred to specialist centres or were retrospective surveys of specialist centre
      experience. This may have resulted in the literature representing a more severe
      group of patients than seen in routine haematological practice. We report on a
      consecutive, unselected cohort of all patients in south and west Wales who
      presented with acquired haemophilia A between 1996 and 2002. There were 18
      patients, an incidence of 1.34/million/year. Compared with previously reported
      cohorts our patients were older, with a median age of 70 years, and less likely
      to have an underlying diagnosis (27%). The bleeding phenotype was less severe,
      with only 27% having life or limb threatening bleeds and 41% required no
      haemostatic treatment. One patient died of bleeding, but three died of
      complications related to immunosuppression. Response to immunosuppression was
      high compared with other series, with 88% of treated patients attaining an
      undetectable inhibitor and normal factor VIII level. These data suggest that
      previously reported cohorts may represent more severely affected patients and,
      whilst guidelines for treatment based on these assumptions may be valid for
      severely affected patients, they may not be universally applicable.

PMID- 14675413
TI  - Molecular mimicry by Helicobacter pylori CagA protein may be involved in the
      pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura.
AB  - The eradication of Helicobacter pylori often leads to platelet recovery in
      patients with chronic idiopathic thrombocytopenic purpura (cITP). Although this
      clinical observation suggests the involvement of H. pylori, little is known about
      the pathogenesis of cITP. We initially examined the effect of H. pylori
      eradication on platelet counts in 20 adult Japanese cITP patients. Then, using
      platelet eluates as the probe in immunoblot analyses, we examined the role of
      molecular mimicry in the pathogenesis of cITP. Helicobacter pylori infection was
      detected in 75% (15 of 20) of cITP patients. Eradication was achieved in 13 (87%)
      of the H. pylori-positive patients, seven (54%) of which showed increased
      platelet counts within the 4 months following treatment. Completely responsive
      patients also showed significant declines in platelet-associated immunoglobulin G
      (PAIgG) levels. Platelet eluates from 12 (nine H. pylori-positive and three H.
      pylori-negative) patients recognized H. pylori cytotoxin-associated gene A (CagA)
      protein, and in three completely responsive patients, levels of anti-CagA
      antibody in platelet eluates declined after eradication therapy. Cross-reactivity
      between PAIgG and H. pylori CagA protein suggests that molecular mimicry by CagA
      plays a key role in the pathogenesis of a subset of cITP patients.

PMID- 14675414
TI  - Clinical relevance of balance between type 1 and type 2 immune responses of
      lymphocyte subpopulations in aplastic anaemia patients.
AB  - Immune dysfunction, which leads to the suppression of haemopoiesis by cytokines
      that are secreted by activated T lymphocytes, is considered to play a key role in
      the pathogenesis of acquired aplastic anaemia (AAA). We investigated the
      intracytoplasmic expression of type-1 [interferon gamma (IFN-gamma), interleukin
      (IL)-2] and type-2 (IL-4, IL-10) cytokines in CD4+ and CD8+ T cells before and
      after in vitro activation in 16 patients with AAA and 17 normal controls.
      Untreated or refractory patients had a significantly higher proportion of
      unstimulated CD4+ and CD8+ T cells that produced IFN-gamma and IL-2 whereas the
      IL-4 and IL-10 producing T cells did not differ from that of controls, resulting
      in a shift of IFN-gamma/IL-4 ratio towards a type-1 response. Patients in
      remission had also increased proportion of IFN-gamma-producing unstimulated CD4+
      and CD8+ cells, with a parallel rise of IL-4- and IL-10-producing cells and
      normal IFN-gamma/IL-4 ratio. These data indicate that, in newly diagnosed and
      refractory patients with AAA, CD4+ cells are polarized towards a type-1 response
      that in turn leads to activation of cytotoxic CD8+ cells and finally to
      haemopoietic stem cell destruction. The type-1 response persists in patients in
      remission although this effect is compensated by the increase of IL-4 and IL-10
      production.

PMID- 14675415
TI  - Eosin-5-maleimide binding to band 3 and Rh-related proteins forms the basis of a
      screening test for hereditary spherocytosis.
AB  - Flow cytometric analysis of eosin-5-maleimide (EMA) binding to red cells is a
      screening test for the diagnosis of hereditary spherocytosis (HS). The present
      study used chemical modifications to determine the integral membrane proteins
      that react with EMA. The predominant interaction of EMA, contributing c. 80% of
      fluorescence, was with the epsilon-NH2 group of lysine in band 3 protein, as
      previously reported. The remainder of the EMA fluorescence was attributable to
      labelling of accessible sulfhydryl groups on intact red cells. This reaction was
      heat labile. Three molecules containing sulfhydryl groups were shown to be
      associated with the Rh blood group protein complex by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis. These were CD47 and the Rh-associated
      glycoprotein, both in the Mr 40-60 kD region, and the Rh blood group proteins in
      the 30-32 kD region. Immunoprecipitation, using specific monoclonal antibodies
      and antibody binding studies by flow cytometry, showed that the relative content
      of these three membrane proteins was lower in HS than normal red cells. Thus, the
      high predictive value of the EMA binding test for HS reflects changes in the
      relative amounts of the Rh-related integral membrane proteins as well as band 3
      in HS red cells.

PMID- 14675416
TI  - Hepatocellular carcinoma in the thalassaemia syndromes.
AB  - Hepatocellular carcinoma (HCC) frequently complicates hepatic cirrhosis secondary
      to viral infection or iron overload. Therefore, patients affected by thalassaemia
      syndromes have a theoretically high risk of developing the tumour. We collected
      data on patients attending Italian centres for the treatment of thalassaemia.
      Twenty-two cases of HCC were identified; 15 were male. At diagnosis, the mean age
      was 45 +/- 11 years and the mean serum ferritin was 1764 +/- 1448 microg/l.
      Eighty-six percent had been infected by hepatitis C virus. Nineteen of 22 cases
      were diagnosed after 1993, suggesting that this problem is becoming more frequent
      with the aging population of thalassaemia patients.

PMID- 14675417
TI  - The Fya, Fy6 and Fy3 epitopes of the Duffy blood group system recognized by new
      monoclonal antibodies: identification of a linear Fy3 epitope.
AB  - Four new anti-Duffy murine monoclonal antibodies (MAbs): two anti-Fy6 (MIMA-107
      and MIMA-108), one anti-Fya (MIMA-19) and one anti-Fy3 (MIMA-29) were
      characterized. Identification of epitopes by means of synthetic peptides
      (Pepscan) showed that the anti-Fy6 reacted most strongly with peptides containing
      the sequence 19QLDFEDV25 of the Duffy glycoprotein, and less strongly with
      peptides containing LDFEDV (MIMA-107) or LDF only (MIMA-108). The anti-Fya
      recognized epitope 38DGDYGA43 containing the Gly42 residue, which defines the Fya
      blood group antigen. MIMA-29 is the first anti-Fy3 reactive with a linear epitope
      281ALDLL285 located in the fourth extracellular domain (ECD4, loop 3) of the
      Duffy glycoprotein. The four new antibodies extend the list of six anti-Fy MAbs
      formerly characterized by Pepscan analysis that allow some general conclusions.
      Fine specificities of various anti-Fya, or anti-Fy6 are not identical, but all of
      them recognize linear epitopes located around, respectively, Gly42 or between two
      potential N-glycosylation sites at Asn16 and Asn27. Anti-Fy3 recognize either a
      linear epitope located in ECD4, or a conformational epitope that includes amino
      acid residues of ECD4 and of other ECDs.

PMID- 14675418
TI  - Decreased hepcidin mRNA expression in thalassemic mice.

PMID- 14675419
TI  - Anticoagulation in pregnancy: a survey of current practice.

PMID- 14675420
TI  - Microtubule organization and function in epithelial cells.
AB  - Microtubules are essential for many aspects of polarity in multicellular
      organisms, ranging from the asymmetric distribution of cell-fate determinants in
      the one-cell embryo to the transient polarity generated in migrating fibroblasts.
      Epithelial cells exhibit permanent cell polarity characterized by apical and
      basolateral surface domains of distinct protein and lipid composition that are
      segregated by tight junctions. They are also endowed with a microtubule network
      that reflects the asymmetry of their cell surface: microtubule minus-ends face
      the apical- and microtubule plus-ends the basal domain. Strikingly, the formation
      of distinct surface domains during epithelial differentiation is accompanied by
      the re-organization of microtubules from a uniform array focused at the
      centrosome to the noncentrosomal network that aligns along the apico-basolateral
      polarity axis. The significance of this coincidence for epithelial morphogenesis
      and the signaling mechanisms that drive microtubule repolymerization in
      developing epithelia remain major unresolved questions that we are only beginning
      to address. Studies in cultured polarized epithelial cells have established that
      microtubules serve as tracks that facilitate targeted vesicular transport. Novel
      findings suggest, moreover, that microtubule-based transport promotes protein
      sorting, and even the generation of transport carriers in the endo- and exocytic
      pathways.

PMID- 14675421
TI  - A karyopherin alpha2 nuclear transport pathway is regulated by glucose in hepatic
      and pancreatic cells.
AB  - We studied the role of the karyopherin alpha2 nuclear import carrier (also known
      as importin alpha2) in glucose signaling. In mhAT3F hepatoma cells, GFP
      karyopherin alpha2 accumulated massively in the cytoplasm within minutes of
      glucose extracellular addition and returned to the nucleus after glucose removal.
      In contrast, GFP-karyopherin alpha1 distribution was unaffected regardless of
      glucose concentration. Glucose increased GFP-karyopherin alpha2 nuclear efflux by
      a factor 80 and its shuttling by a factor 4. These glucose-induced movements were
      not due to glycolytic ATP production. The mechanism involved was leptomycin B
      insensitive, but phosphatase- and energy-dependent. HepG2 and COS-7 cells
      displayed no glucose-induced GFP-karyopherin alpha2 movements. In pancreatic MIN
      6 cells, the glucose-induced movements of karyopherin alpha2 and the stimulation
      of glucose-induced gene transcription were simultaneously lost between passages
      28 and 33. Thus, extracellular glucose regulates a nuclear transport pathway by
      increasing the nuclear efflux and shuttling of karyopherin alpha2 in cells in
      which glucose can stimulate the transcription of sugar-responsive genes.

PMID- 14675422
TI  - Stimulation-dependent recycling of integrin beta1 regulated by ARF6 and Rab11.
AB  - In comparison to the internalization pathways of endocytosis, the recycling
      pathways are less understood. Even less defined is the process of regulated
      recycling, as few examples exist and their underlying mechanisms remain to be
      clarified. In this study, we examine the endocytic recycling of integrin beta1, a
      process that has been suggested to play an important role during cell motility by
      mediating the redistribution of integrins to the migrating front. External
      stimulation regulates the endocytic itinerary of beta1, mainly at an internal
      compartment that is likely to be a subset of the recycling endosomes. This
      stimulation-dependent recycling is regulated by ARF6 and Rab11, and also requires
      the actin cytoskeleton in an ARF6-dependent manner. Consistent with these
      observations being relevant for cell motility, mutant forms of ARF6 that affect
      either actin rearrangement or recycling inhibit the motility of a breast cancer
      cell line.

PMID- 14675423
TI  - Plasma membrane targeting of podocin through the classical exocytic pathway:
      effect of NPHS2 mutations.
AB  - Podocytes are specialized epithelial cells of the glomerulus in the kidney, which
      interconnect at the top of the glomerular basement membrane through the slit
      diaphragm, an adherens-like junction that plays a crucial role in the glomerular
      filtration process. Podocin, a plasma membrane anchored stomatin-like protein, is
      expressed in lipid rafts at the insertion of the slit diaphragm in podocytes.
      Mutations in NPHS2, the gene encoding podocin, are associated with inherited and
      sporadic cases of steroid-resistant nephrotic syndrome. Here, we show that
      brefeldin A induces accumulation of newly synthesized podocin in the endoplasmic
      reticulum, suggesting that podocin biosynthesis follows the classical secretory
      pathway, and we study the effect of 12 NPHS2 mutations associated with steroid
      resistant nephrotic syndrome on the trafficking of the protein. We found that 9
      podocin mutants were not targeted to the plasma membrane, 8 being retained in the
      endoplasmic reticulum and one being localized in late endosomes. Furthermore, by
      screening our database of patients with NPHS2 mutations, we found that podocin
      mutants retained in the endoplasmic reticulum are associated with earlier onset
      of the disease than those correctly targeted to the cell membrane. Our data
      suggest that most of NPHS2 mutations lead to retention of podocin in the
      endoplasmic reticulum and therefore provide a rationale for devising therapeutic
      approaches aimed at correcting the protein processing defect.

PMID- 14675424
TI  - A complete set of SNAREs in yeast.
AB  - Trafficking of cargo molecules through the secretory pathway relies on packaging
      and delivery of membrane vesicles. These vesicles, laden with cargo, carry
      integral membrane proteins that can determine with which target membrane the
      vesicle might productively fuse. The membrane fusion process is highly conserved
      in all eukaryotes and the central components driving membrane fusion events
      involved in vesicle delivery to target membranes are a set of integral membrane
      proteins called SNAREs. The yeast Saccharomyces cerevisiae has served as an
      extremely useful model for characterizing components of membrane fusion through
      genetics, biochemistry and bioinformatics, and it is now likely that the complete
      set of SNAREs is at hand. Here, we present the details from the searches for
      SNAREs, summarize the domain structures of the complete set, review what is known
      about localization of SNAREs to discrete membranes, and highlight some of the
      surprises that have come from the search.

PMID- 14675425
TI  - Sorting ourselves out: seeking consensus on trafficking in the beta-cell.
AB  - Biogenesis of the regulated secretory pathway in the pancreatic beta-cell
      involves packaging of products, notably proinsulin, into immature secretory
      granules derived from the trans-Golgi network. Proinsulin is converted to insulin
      and C-peptide as granules mature. Secretory proteins not entering granules are
      conveyed by transport intermediates directly to the plasma membrane for
      constitutive secretion. One of the co-authors, Peter Arvan, has proposed that in
      addition, small vesicles bud from granules to traffic to the endosomal system.
      From there, some proteins are secreted by a (post-granular) constitutive-like
      pathway. He argues that retention in granules is facilitated by condensation,
      rendering soluble products (notably C-peptide and proinsulin) more available for
      constitutive-like secretion. Thus he argues that prohormone conversion is
      potentially important in secretory granule biogenesis. The other co-author,
      Philippe Halban, argues that the post-granular secretory pathway is not of
      physiological relevance in primary beta-cells, and contests the importance of
      proinsulin conversion for retention in granules. Both, however, agree that
      trafficking from granules to endosomes is important, purging granules of unwanted
      newly synthesized proteins and allowing their traffic to other destinations. In
      this Traffic Interchange, the two co-authors attempt to reconcile their
      differences, leading to a common vision of proinsulin trafficking in primary and
      transformed cells.

PMID- 14675427
TI  - Molecular cloning and characterization of a cDNA encoding ent-cassa-12,15-diene
      synthase, a putative diterpenoid phytoalexin biosynthetic enzyme, from suspension
      cultured rice cells treated with a chitin elicitor.
AB  - We have isolated and characterized a cDNA encoding a novel diterpene cyclase,
      OsDTC1, from suspension-cultured rice cells treated with a chitin elicitor.
      OsDTC1 functions as ent-cassa-12,15-diene synthase, which is considered to play a
      key role in the biosynthesis of (-)-phytocassanes recently isolated as rice
      diterpenoid phytoalexins. The expression of OsDTC1 mRNA was also confirmed in
      ultraviolet (UV)-irradiated rice leaves. In addition, we identified ent-cassa
      12,15-diene, a putative diterpene hydrocarbon precursor of (-)-phytocassanes, as
      an endogenous compound in the chitin-elicited suspension-cultured rice cells and
      the UV-irradiated rice leaves. The OsDTC1 cDNA isolated here will be a useful
      tool to investigate the regulatory mechanisms of the biosynthesis of (-)
      phytocassanes in rice.

PMID- 14675428
TI  - Characterisation of an Arabidopsis-Leptosphaeria maculans pathosystem: resistance
      partially requires camalexin biosynthesis and is independent of salicylic acid,
      ethylene and jasmonic acid signalling.
AB  - Out of 168 Arabidopsis accessions screened with isolates of Leptosphaeria
      maculans, one (An-1) showed clear disease symptoms. In order to identify
      additional components involved in containment of L. maculans in Arabidopsis, a
      screen for L. maculans-susceptible (lms) mutants was performed. Eleven lms
      mutants were isolated, which displayed differential susceptibility responses to
      L. maculans. lms1 was crossed with Columbia (Col-0) and Ws-0, and mapping data
      for both populations showed the highest linkage to a region on chromosome 2.
      Reduced levels of PR-1 and PDF1.2 expression were found in lms1 compared to wild
      type plants 48 h after pathogen inoculation. In contrast, the lms1 mutant
      displayed upregulation of either marker gene upon chemical treatment, possibly as
      an effect of an altered ethylene (ET) response. To assess the contribution of
      different defence pathways, genotypes implicated in salicylic acid (SA)
      signalling plants expressing the bacterial salicylate hydroxylase (nahG) gene,
      non-expressor of PR1 (npr1)-1 and phytoalexin-deficient (pad4-1), jasmonic acid
      (JA) signalling (coronatine insensitive (coi)1-16, enhanced disease
      susceptibility (eds)8-1 and jasmonic acid resistant (jar)1-1) and ET signalling
      (eds4-1, ethylene insensitive (ein)2, ein3-1 and ethylene resistant (etr)1-1)
      were screened. All the genotypes screened were as resistant as wild-type plants,
      demonstrating the dispensability of the pathways in L. maculans resistance. When
      mutants implicated in cell death responses were assayed, responsive to antagonist
      1 (ran1)-1 exhibited a weak susceptible phenotype, whereas accelerated cell death
      (acd)1-20 showed a rapid lesion development. Camalexin is only partially
      responsible for L. maculans containment in Arabidopsis, as pad3-1 and enhanced
      susceptibility to Alternaria (esa)1 clearly showed a susceptible response while
      wild-type levels of camalexin were present in An-1 and lms1. The data presented
      point to the existence of multiple defence mechanisms controlling the containment
      of L. maculans in Arabidopsis.

PMID- 14675429
TI  - Enhancement of stress tolerance in transgenic tobacco plants overexpressing
      Chlamydomonas glutathione peroxidase in chloroplasts or cytosol.
AB  - To evaluate the physiological potential of the defense system against
      hydroperoxidation of membrane-lipid components caused by environmental stresses
      in higher plants, we generated transgenic tobacco plants expressing a glutathione
      peroxidase (GPX)-like protein in the cytosol (TcGPX) or chloroplasts (TpGPX). The
      activities toward alpha-linolenic acid hydroperoxide in TcGPX and TpGPX plants
      were 47.5-75.3 and 32.7-42.1 nM min(-1) mg(-1) protein, respectively, while no
      activity was detected in wild-type plants. The transgenic plants showed increased
      tolerance to oxidative stress caused by application of methylviologen (MV: 50
      microM) under moderate light intensity (200 micro E m(-2) sec(-1)), chilling
      stress under high light intensity (4 degrees C, 1000 microE m(-2) sec(-1)), or
      salt stress (250 mM NaCl). Under these stresses, the lipid hydroperoxidation (the
      production of malondialdehyde (MDA)) of the leaves of TcGPX and TpGPX plants was
      clearly suppressed compared with that of wild-type plants. Furthermore, the
      capacity of the photosynthetic and antioxidative systems in the transgenic plants
      remained higher than those of wild-type plants under chilling or salt stress.
      These results clearly indicate that a high level of GPX-like protein in tobacco
      plants functions to remove unsaturated fatty acid hydroperoxides generated in
      cellular membranes under stress conditions, leading to the maintenance of
      membrane integrity and increased tolerance to oxidative stress caused by various
      stress conditions.

PMID- 14675430
TI  - Potato lectin: an updated model of a unique chimeric plant protein.
AB  - A complete cDNA encoding a potato tuber lectin has been identified and sequenced.
      Based on the deduced amino acid sequence, the still enigmatic molecular structure
      of the classical chimeric potato lectin could eventually be determined.
      Basically, the potato lectin consists of two nearly identical chitin-binding
      modules, built up of two in-tandem arrayed hevein domains that are interconnected
      by an extensin-like domain of approximately 60 amino acid residues. Although this
      structure confirms the 'canonical' chimeric nature of the Solanaceae lectins, it
      differs fundamentally from all previously proposed models. The new insights in
      the structure are also discussed in view of the physiological role of the
      Solanaceae lectins.

PMID- 14675431
TI  - The tomato resistance protein Bs4 is a predicted non-nuclear TIR-NB-LRR protein
      that mediates defense responses to severely truncated derivatives of AvrBs4 and
      overexpressed AvrBs3.
AB  - The Lycopersicon esculentum Bs4 resistance (R) gene specifies recognition of
      Xanthomonas campestris pv. vesicatoria (Xcv) strains that express the cognate
      AvrBs4 avirulence protein. Bs4 was isolated by positional cloning and is
      predicted to encode a nucleotide-binding leucine-rich repeat (NB-LRR) protein
      that is homologous to tobacco N and potato Y-1 resistance proteins. Xcv infection
      tests demonstrate that Bs4 confers perception of AvrBs4 but not the 97% identical
      AvrBs3 protein. However, when delivered via Agrobacterium T-DNA transfer, both,
      avrBs4 and avrBs3 trigger a Bs4-dependent hypersensitive response, indicating
      that naturally occurring AvrBs3-homologues provide a unique experimental platform
      for molecular dissection of recognition specificity. Transcript studies revealed
      intron retention in Bs4 transcripts. Yet, an intron-deprived Bs4 derivative still
      mediates AvrBs4 detection, suggesting that the identified splice variants are not
      crucial to resistance. The L. pennellii bs4 allele, which is >98% identical to L.
      esculentum Bs4, has a Bs4-like exon-intron structure with exception of a splice
      polymorphism in intron 2 that causes truncation of the predicted bs4 protein. To
      test if the receptor-ligand model is a valid molecular description of Bs4
      mediated AvrBs4 perception, we conducted yeast two-hybrid studies. However, a
      direct interaction was not observed. Defense signaling of the Bs4-governed
      reaction was studied in Nicotiana benthamiana by virus-induced gene silencing and
      showed that Bs4-mediated resistance is EDS1- and SGT1-dependent.

PMID- 14675432
TI  - Organisation of the pantothenate (vitamin B5) biosynthesis pathway in higher
      plants.
AB  - Pantothenate (vitamin B5) is the precursor for the biosynthesis of the
      phosphopantetheine moiety of coenzyme A and acyl carrier protein, and is
      synthesised in Escherichia coli by four enzymic reactions. Ketopantoate
      hydroxymethyltransferase (KPHMT) and pantothenate synthetase (PtS) catalyse the
      first and last steps, respectively. Two genes encoding KPHMT and one for PtS were
      identified in the Arabidopsis thaliana genome, and cDNAs for all three genes were
      amplified by PCR. The cDNAs were able to complement their respective E. coli
      auxotrophs, demonstrating that they encoded functional enzymes. Subcellular
      localisation of the proteins was investigated using green fluorescent protein
      (GFP) fusions and confocal microscopy. The two KPHMT-GFP fusion proteins were
      targeted exclusively to mitochondria, whereas PtS-GFP was found in the cytosol.
      This implies that there must be transporters for pathway intermediates. KPHMT
      enzyme activity could be measured in purified mitochondria from both pea leaves
      and Arabidopsis suspension cultures. We investigated whether Arabidopsis encoded
      homologues of the remaining two pantothenate biosynthesis enzymes from E. coli, l
      aspartate-alpha-decarboxylase (ADC) and ketopantoate reductase (KPR). No
      homologue of ADC could be identified using either conventional blast or searches
      with the program fugue in which the structure of the E. coli ADC was compared to
      all the annotated proteins in Arabidopsis. ADC also appears to be absent from the
      genome of the yeast, Saccharomyces cerevisiae, by the same criteria. In contrast,
      a putative Arabidopsis oxidoreductase with some similarity to KPR was identified
      with fugue.

PMID- 14675433
TI  - The FUS3 transcription factor functions through the epidermal regulator TTG1
      during embryogenesis in Arabidopsis.
AB  - Loss-of-function mutations in the FUSCA3 (FUS3) gene of Arabidopsis result in
      alterations in cotyledon identity, inability to complete late seed maturation
      processes, and the premature activation of apical and root embryonic meristems,
      which indicates that this transcription factor is an essential regulator of
      embryogenesis. Although FUS3 shows a complex pattern of expression in the embryo,
      this gene is only required in the protoderm to carry out its functions. Moreover,
      the epidermal morphogenesis regulator TRANSPARENT TESTA GLABRA1 (TTG1) is
      negatively regulated by FUS3 in the embryo. When a loss-of-function ttg1 mutation
      is introduced into a fus3 mutant, a number of fus3-related phenotypes are
      rescued, indicating a functional TTG1 gene is required to manifest the fus3
      mutant phenotype. It therefore appears that one of the functions of FUS3 is to
      restrict the domain of expression of TTG1 during embryogenesis. The FUS3-TTG1
      interaction is both maternal and zygotic, suggesting a complex relationship is
      required between these gene products to allow correct seed development.

PMID- 14675434
TI  - Dual functionality of a plant U-rich intronic sequence element.
AB  - In potato invertase genes, the constitutively included, 9-nucleotide (nt)-long
      mini-exon requires a strong branchpoint and U-rich polypyrimidine tract for
      inclusion. The strength of these splicing signals was demonstrated by greatly
      enhanced splicing of a poorly spliced intron and by their ability to support
      splicing of an artificial mini-exon, following their introduction. Plant introns
      also require a second splicing signal, UA-rich intronic elements, for efficient
      intron splicing. Mutation of the branchpoint caused loss of mini-exon inclusion
      without loss of splicing enhancement, showing that the same U-rich sequence can
      function as either a polypyrimidine tract or a UA-rich intronic element. The
      distinction between the splicing signals depended on intron context (the presence
      or absence of an upstream, adjacent and functional branchpoint), and on the
      sequence context of the U-rich elements. Polypyrimidine tracts tolerated C
      residues while UA-rich intronic elements tolerated As. Thus, in plant introns, U
      rich splicing elements can have dual roles as either a general plant U-rich
      splicing signal or a polypyrimidine tract. Finally, overexpression of two
      different U-rich binding proteins enhanced intron recognition significantly.
      These results highlight the importance of co-operation between splicing signals,
      the importance of other nucleotides within U-rich elements for optimal binding of
      competing splicing factors and effects on splicing efficiency of U-rich binding
      proteins.

PMID- 14675435
TI  - A mutation in the nuclear-encoded plastid ribosomal protein S9 leads to early
      embryo lethality in maize.
AB  - Seeds of the lethal embryo 1 (lem1) mutant in maize (Zea mays) display a non
      concordant lethal phenotype: whereas the embryo aborts very early, before the
      transition stage, the endosperm develops almost normally. The mutant was
      identified in a collection of maize lines that carried the transposon Activation
      (Ac) at different locations in the genome. Co-segregation and reversion analysis
      showed that lem1 was tagged by Ac. The lem1 gene encodes a protein that is highly
      similar to the rice plastid 30S ribosomal protein S9 (PRPS9). lem1 maps to
      chromosome 1L and appears to be the only copy of prps9 in the maize genome. Green
      fluorescent protein (GFP) fusion constructs containing only the putative transit
      peptide (TP) of LEM1 localize exclusively to the plastids, confirming that the
      LEM1 protein is a PRP. In contrast, GFP fusion constructs containing the entire
      LEM1 protein co-localize to the plastids and to the nucleus, suggesting a
      possible dual function for this protein. Two alternative, although not mutually
      exclusive, explanations are considered for the lem phenotype of the lem1 mutant:
      (i) functional plastids are required for normal embryo development; and (ii) the
      PRPS9 has an extra-ribosomal function required for embryogenesis.

PMID- 14675436
TI  - TRANSPARENT TESTA 19 is involved in the accumulation of both anthocyanins and
      proanthocyanidins in Arabidopsis.
AB  - Flavonoid compounds such as anthocyanins and proanthocyanidins (PAs; so-called
      condensed tannins) have a multitude of functions in plants. They must be
      transported from the site of synthesis in the cytosol to their final destination,
      the vacuoles. Three models have been proposed for sequestering anthocyanins in
      vacuoles, but the transport machinery for PAs is poorly understood. Novel
      Arabidopsis mutants, transparent testa 19 (tt19), which were induced by ion beam
      irradiation, showed a great reduction of anthocyanin pigments in the vegetative
      parts as well as brown pigments in the seed coat. The TT19 gene was isolated by
      chromosome walking and a candidate gene approach, and was shown to be a member of
      the Arabidopsis glutathione S-transferase (GST) gene family. Heterologous
      expression of a putative ortholog, petunia anthocyanin 9 (AN9), in tt19
      complemented the anthocyanin accumulation but not the brown pigmentation in the
      seed coat. This suggests that the TT19 gene is required for vacuolar uptake of
      anthocyanins into vacuoles, but that it has also a function different from that
      of AN9. The depositional pattern of PA precursors in the mutant was different
      from that in the wild type. These results indicate that TT19 participates in the
      PA pathway as well as the anthocyanin pathway of Arabidopsis. As involvement of
      GST in the PA pathway was previously considered unlikely, the function of TT19 in
      the PA pathway is also discussed in the context of the putative transporter for
      PA precursors.

PMID- 14675437
TI  - Overexpression of the rice Osmyb4 gene increases chilling and freezing tolerance
      of Arabidopsis thaliana plants.
AB  - The expression of the gene Osmyb4, detected at low level in rice (Oryza sativa)
      coleoptiles grown for 3 days at 29 degrees C, is strongly induced by treatments
      at 4 degrees C. At sublethal temperatures of 10 and 15 degrees C, its expression
      in rice seedlings is already evident, but this effect cannot be vicariated by
      other stresses or ABA treatment. We demonstrate by transient expression that Myb4
      transactivates the PAL2, ScD9 SAD and COR15a cold-inducible promoters. The Osmyb4
      function in vivo is demonstrated overexpressing its cDNA in Arabidopsis thaliana
      plants (ecotype Wassilewskija) under the control of the constitutive CaMV 35S
      promoter. Myb4 overexpressing plants show a significant increased cold and
      freezing tolerance, measured as membrane or Photosystem II (PSII) stability and
      as whole plant tolerance. Finally, in Osmyb4 transgenic plants, the expression of
      genes participating in different cold-induced pathways is affected, suggesting
      that Myb4 represents a master switch in cold tolerance.

PMID- 14675438
TI  - Expression of cytokinin biosynthetic isopentenyltransferase genes in Arabidopsis:
      tissue specificity and regulation by auxin, cytokinin, and nitrate.
AB  - The rate-limiting step of cytokinin biosynthesis in Arabidopsis thaliana Heynh.
      is catalyzed by ATP/ADP isopentenyltransferases, A. thaliana IsoPentenyl
      Transferase (AtIPT)1, and AtIPT4, and by their homologs AtIPT3, AtIPT5, AtIPT6,
      AtIPT7, and AtIPT8. To understand the dynamics of cytokinins in plant
      development, we comprehensively analyzed the expression of isopentenyltransferase
      genes of Arabidopsis. Examination of their mRNA levels and the expression
      patterns of the beta-glucuronidase (GUS) gene fused to the regulatory sequence of
      each AtIPT gene revealed a specific expression pattern of each gene. The
      predominant expression patterns were as follows: AtIPT1::GUS, xylem precursor
      cell files in the root tip, leaf axils, ovules, and immature seeds; AtIPT3::GUS,
      phloem tissues; AtIPT4::GUS and AtIPT8::GUS, immature seeds with highest
      expression in the chalazal endosperm (CZE); AtIPT5::GUS, root primordia,
      columella root caps, upper part of young inflorescences, and fruit abscission
      zones; AtIPT7::GUS, endodermis of the root elongation zone, trichomes on young
      leaves, and some pollen tubes. AtIPT1, AtIPT3, AtIPT5, and AtIPT7 were
      downregulated by cytokinins within 4 h. AtIPT5 and AtIPT7 was upregulated by
      auxin within 4 h in roots. AtIPT3 was upregulated within 1 h after an application
      of nitrate to mineral-starved Arabidopsis plants. The upregulation by nitrate did
      not require de novo protein synthesis. We also examined the expression of two
      genes for tRNA isopentenyltransferases, AtIPT2 and AtIPT9, which can also be
      involved in cytokinin biosynthesis. They were expressed ubiquitously, with
      highest expression in proliferating tissues. These findings are discussed in
      relation to the role of cytokinins in plant development.

PMID- 14675439
TI  - A new method for rapid visualization of defects in leaf cuticle reveals five
      intrinsic patterns of surface defects in Arabidopsis.
AB  - The epidermis of higher plants generates the cuticle layer that covers the outer
      surface of each plant. The cuticle plays a crucial role in plant development, and
      some mutants with defective cuticle exhibit morphological abnormalities, such as
      the fusion of organs. The way in which the cuticle forms and its contribution to
      morphogenesis are poorly understood. Conventional detection of the cuticle by
      transmission electron microscopy (TEM) requires laborious procedures, which
      include fixation, staining with osmium, and preparation of ultra-thin sections.
      It is also difficult to survey entire surfaces of expanded leaves because of the
      limited size of specimens that can be examined. Thus, TEM is unsuitable for large
      scale screening for mutants with defective cuticle. We describe here a rapid and
      inexpensive method, designated the toluidine-blue (TB) test, for detection of
      cuticular defects in whole leaves. We demonstrated the validity of the TB test
      using mutants of Arabidopsis thaliana, including abnormal leaf shape1 (ale1),
      fiddlehead (fdh), and five eceriferum (cer) mutants, in which the structure
      and/or function of the cuticle is abnormal. Genetic screening for mutants using
      the TB test allowed us to identify seven loci. The cuticle-defective regions of
      leaves of the mutants revealed five intrinsic patterns of surface defects
      (classes I through V), suggesting that formation of functional cuticle on leaves
      involves various spatially regulated factors.

PMID- 14675440
TI  - Characterisation of a pine MYB that regulates lignification.
AB  - A member of the R2R3-MYB family of transcription factors was cloned from a cDNA
      library constructed from RNA isolated from differentiating pine xylem. This MYB,
      Pinus taeda MYB4 (PtMYB4), is expressed in cells undergoing lignification, as
      revealed by in situ RT-PCR. Electrophoretic mobility shift assays (EMSAs) showed
      that recombinant PtMYB4 protein is able to bind to DNA motifs known as AC
      elements. AC elements are ubiquitous in the promoters of genes encoding lignin
      biosynthetic enzymes. Transcriptional activation assays using yeast showed that
      PtMYB4 could activate transcription in an AC-element-dependent fashion.
      Overexpression of PtMYB4 in transgenic tobacco plants altered the accumulation of
      transcripts corresponding to genes encoding lignin biosynthetic enzymes. Lignin
      deposition increased in transgenic tobacco plants that overexpressed PtMYB4, and
      extended to cell types that do not normally lignify. Taken together, these
      findings are consistent with the hypothesis that PtMYB4 is sufficient to induce
      lignification, and that it may play this role during wood formation in pine.

PMID- 14675441
TI  - Potato virus Y NIa protease activity is not sufficient for elicitation of Ry
      mediated disease resistance in potato.
AB  - Ry confers extreme resistance (ER) to all strains of potato virus Y (PVY). In
      previous work, we have shown that the protease domain of the nuclear inclusion a
      protease (NIaPro) from PVY is the elicitor of the Ry-mediated resistance and that
      integrity of the protease active site is required for the elicitation of the
      resistance response. Two possibilities arise from these results: first, the
      structure of the active protease has elicitor activity; second, NIa-mediated
      proteolysis is required to elicit the resistance response. To resolve these
      possibilities, the NIaPro from PVY was randomly mutagenised and the clones
      obtained were screened for elicitation of cell death as an indicator of
      resistance and proteolytic activity. We did not find any mutants that had
      retained the ability to elicit cell death but had lost protease activity, as
      measured by processing of the NIa cleavage site in the viral genome. This was
      consistent with the idea that protease activity is necessary for elicitor
      activity. However, protease activity was not sufficient because we found three
      elicitor-defective mutants in which there was a high level of protease activity
      in this assay.

PMID- 14675442
TI  - Anionic lipids are required for chloroplast structure and function in
      Arabidopsis.
AB  - Photosynthetic membranes of plants primarily contain non-phosphorous glycolipids.
      The exception is phosphatidylglycerol (PG), which is an acidic/anionic
      phospholipid. A second major anionic lipid in chloroplasts is the sulfolipid
      sulfoquinovosyldiacylglycerol (SQDG). It is hypothesized that under severe
      phosphate limitation, SQDG substitutes for PG, ensuring a constant proportion of
      anionic lipids even under adverse conditions. A newly constructed SQDG and PG
      deficient double mutant supports this hypothesis. This mutant, sqd2 pgp1-1,
      carries a T-DNA insertion in the structural gene for SQDG synthase (SQD2) and a
      point mutation in the structural gene for phosphatidylglycerolphosphate synthase
      (PGP1). In the sqd2 pgp1-1 double mutant, the fraction of total anionic lipids is
      reduced by approximately one-third, resulting in pale yellow cotyledons and
      leaves with reduced chlorophyll content. Photoautotrophic growth of the double
      mutant is severely compromised, and its photosynthetic capacity is impaired. In
      particular, photosynthetic electron transfer at the level of photosystem II
      (PSII) is affected. Besides these physiological changes, the mutant shows altered
      leaf structure, a reduced number of mesophyll cells, and ultrastructural changes
      of the chloroplasts. All observations on the sqd2 pgp1-1 mutant lead to the
      conclusion that the total content of anionic thylakoid lipids is limiting for
      chloroplast structure and function, and is critical for overall photoautotrophic
      growth and plant development.

PMID- 14675443
TI  - Synthesis of ketocarotenoids in the seed of Arabidopsis thaliana.
AB  - A cDNA coding for a gene necessary for synthesis of ketocarotenoids was cloned
      from the alga Haematococcus pluvialis and expressed in the seed of Arabidopsis
      thaliana. The expression of the algal beta-carotene-oxygenase gene was directed
      to the seed by use of the 2S, seed storage protein promoter napA. Extracts from
      seeds of the transgenic plants were clearly red because of accumulation of
      ketocarotenoids, and free and esterified forms of ketocarotenoids were found in
      addition to the normal carotenoid composition in the seed. The major
      ketocarotenoids in the transgenic plants were: 4-keto-lutein (3,3'-dihydroxy-beta
      ,epsilon-carotene-4-one), adonirubin (3-hydroxy-beta-,beta'-carotene-4,4'-dione)
      and canthaxanthin (beta-,beta'-carotene-4,4'-dione). 4-Keto-lutein differs from
      the more common adonixanthin only in the position of one double bond. To increase
      the substrate availability for the beta-carotene-oxygenase, these transformants
      were crossed with transgenic plants overexpressing a construct of an endogenous
      phytoene synthase gene, also under the control of the napA promoter. The
      resulting crossings gave rise to seeds with a 4.6-fold relative increase of the
      total pigment, and the three major ketocarotenoids were increased 13-fold
      compared to seeds of transgenic plants carrying only the beta-carotene-oxygenase
      construct.

PMID- 14675444
TI  - Identification of novel cis-acting elements, IDE1 and IDE2, of the barley IDS2
      gene promoter conferring iron-deficiency-inducible, root-specific expression in
      heterogeneous tobacco plants.
AB  - The molecular mechanisms of plant responses to iron (Fe) deficiency remain
      largely unknown. To identify the cis-acting elements responsible for Fe
      deficiency-inducible expression in higher plants, the barley IDS2 (iron
      deficiency specific clone no. 2) gene promoter was analyzed using a transgenic
      tobacco system. Deletion analysis revealed that the sequence between -272 and -91
      from the translational start site (-272/-91) was both sufficient and necessary
      for specific expression in tobacco roots. Further deletion and linker-scanning
      analysis of this region clearly identified two cis-acting elements: iron
      deficiency-responsive element 1 (IDE1) at -153/-136 (ATCAAGCATGCTTCTTGC) and IDE2
      at -262/-236 (TTGAACGGCAAGTTTCACGCTGTCACT). The co-existence of IDE1 and IDE2 was
      essential for specific expression when the -46/+8 region (relative to the
      transcriptional start site) of the CaMV 35S promoter was used as a minimal
      promoter. Expression occurred mainly in the root pericycle, endodermis, and
      cortex. When the -90/+8 region of the CaMV 35S promoter was fused, the -272/-227
      region, which consists of IDE2 and an additional 19 bp, could drive Fe-deficiency
      inducible expression without IDE1 throughout almost the entire root. The
      principal modules of IDE1 and IDE2 were homologous. Sequences homologous to IDE1
      were also found in many other Fe-deficiency-inducible promoters, including:
      nicotianamine aminotransferase (HvNAAT)-A, HvNAAT-B, nicotianamine synthase
      (HvNAS1), HvIDS3, OsNAS1, OsNAS2, OsIRT1, AtIRT1, and AtFRO2, suggesting the
      conservation of cis-acting elements in various genes and species. The
      identification of novel cis-acting elements, IDE1 and IDE2, will provide powerful
      tools to clarify the molecular mechanisms regulating Fe homeostasis in higher
      plants.

PMID- 14675445
TI  - Antisense LOX expression increases herbivore performance by decreasing defense
      responses and inhibiting growth-related transcriptional reorganization in
      Nicotiana attenuata.
AB  - Inhibition of jasmonic acid (JA) signaling has been shown to decrease herbivore
      resistance, but the responsible mechanisms are largely unknown because insect
      resistance is poorly understood in most model plant systems. We characterize
      three members of the lipoxygenase (LOX) gene family in the native tobacco plant
      Nicotiana attenuata and manipulate, by antisense expression, a specific, wound-
      and herbivory-induced isoform (LOX3) involved in JA biosynthesis. In three
      independent lines, antisense expression reduced wound-induced JA accumulation but
      not the release of green leaf volatiles (GLVs). The impaired JA signaling reduced
      two herbivore-induced direct defenses, nicotine and trypsin protease inhibitors
      (TPI), as well as the potent indirect defense, the release of volatile terpenes
      that attract generalist predators to feeding herbivores. All these defenses could
      be fully restored by methyl-JA (MeJA) treatment, with the exception of the
      increase in TPI activity, which was partially restored, suggesting the
      involvement of additional signals. The impaired ability to produce chemical
      defenses resulted in lower resistance to Manduca sexta attack, which could also
      be restored by MeJA treatment. Expression analysis using a cDNA microarray,
      specifically designed to analyze M. sexta-induced gene expression in N.
      attenuata, revealed a pivotal role for LOX3-produced oxylipins in upregulating
      defense genes (protease inhibitor, PI; xyloglucan endotransglucosylase/hydrolase,
      XTH; threonine deaminase, TD; hydroperoxide lyase, HPL), suppressing both
      downregulated growth genes (RUBISCO and photosystem II, PSII) and upregulated
      oxylipin genes (alpha-dioxygenase, alpha-DOX). By genetically manipulating
      signaling in a plant with a well-characterized ecology, we demonstrate that the
      complex phenotypic changes that mediate herbivore resistance are controlled by a
      specific part of the oxylipin cascade.

PMID- 14675446
TI  - (R,S)-Reticuline 7-O-methyltransferase and (R,S)-norcoclaurine 6-O
      methyltransferase of Papaver somniferum - cDNA cloning and characterization of
      methyl transfer enzymes of alkaloid biosynthesis in opium poppy.
AB  - S-Adenosyl-L-methionine:(R,S)-reticuline 7-O-methyltransferase converts
      reticuline to laudanine in tetrahydrobenzylisoquinoline biosynthesis in the opium
      poppy Papaver somniferum. This enzyme activity has not yet been detected in
      plants. A proteomic analysis of P. somniferum latex identified a gel spot that
      contained a protein(s) whose partial amino acid sequences were homologous to
      those of plant O-methyltransferases. cDNA was amplified from P. somniferum RNA by
      reverse transcription PCR using primers based on these internal amino acid
      sequences. Recombinant protein was then expressed in Spodoptera frugiperda Sf9
      cells in a baculovirus expression vector. Steady-state kinetic measurements with
      one heterologously expressed enzyme and mass spectrometric analysis of the
      enzymatic products suggested that this unusual enzyme is capable of carrying
      through sequential O-methylations on the isoquinoline and on the benzyl moiety of
      several substrates. The tetrahydrobenzylisoquinolines (R)-reticuline (4.2 sec(-1)
      mm(-1)), (S)-reticuline (4.5 sec(-1) mm(-1)), (R)-protosinomenine (1.7 sec(-1)
      mm(-1)), and (R,S)-isoorientaline (1.4 sec(-1) mm(-1)) as well as guaiacol (5.9
      sec(-1) mm(-1)) and isovanillic acid (1.2 sec(-1) mm(-1)) are O-methylated by the
      enzyme with the ratio kcat/K m shown in parentheses. A P. somniferum cDNA
      encoding (R,S)-norcoclaurine 6-O-methyltransferase was similarly isolated and
      characterized. This enzyme was less permissive, methylating only (R,S)
      norcoclaurine (7.4 sec(-1) mm(-1)), (R)-norprotosinomenine (4.1 sec(-1) mm(-1)),
      (S)-norprotosinomenine (4.0 sec(-1) mm(-1)) and (R,S)-isoorientaline (1.0 sec(-1)
      mm(-1)). A phylogenetic comparison of the amino acid sequences of these O
      methyltransferases to those from 28 other plant species suggests that these
      enzymes group more closely to isoquinoline biosynthetic O-methyltransferases from
      Coptis japonica than to those from Thalictrum tuberosum that can O-methylate both
      alkaloid and phenylpropanoid substrates.

PMID- 14675447
TI  - Spermine signalling in tobacco: activation of mitogen-activated protein kinases
      by spermine is mediated through mitochondrial dysfunction.
AB  - Polyamines (PAs) play important roles in cell proliferation, growth and
      environmental stress responses of all living organisms. In this study, we examine
      whether these compounds act as signal mediators. Spermine (Spm) specifically
      activated protein kinases of tobacco leaves, which were identified as salicylic
      acid (SA)-induced protein kinase (SIPK) and wound-induced protein kinase (WIPK),
      using specific antibodies. Upon Spm treatment, upregulation of WIPK, but not
      SIPK, was observed. Spm-induced mitogen-activated protein kinases (MAPKs)
      activation and WIPK upregulation were prevented upon pre-treatment with
      antioxidants and Ca2+ channel blockers. Additionally, Spm specifically stimulated
      expression of the alternative oxidase (AOX) gene, which was disrupted by these
      antioxidants and Ca2+ channel blockers. Bongkrekic acid (BK), an inhibitor of the
      opening of mitochondrial permeability transition (PT) pores, suppressed MAPKs
      activation and accumulation of WIPK and AOX mRNA. Our data collectively suggest
      that Spm causes mitochondrial dysfunction via a signalling pathway in which
      reactive oxygen species and Ca2+ influx are involved. As a result, the
      phosphorylation activities of the two MAPK enzymes SIPK and WIPK are stimulated.

PMID- 14675448
TI  - Stress-responsive zinc finger gene ZPT2-3 plays a role in drought tolerance in
      petunia.
AB  - The petunia gene, ZPT2-3, encodes a Cys2/His2-type zinc finger protein. Here, we
      describe the expression of ZPT2-3 in response to various stresses and the effects
      of ZPT2-3 overexpression in transgenic petunia. Mechanical wounding induced
      accumulation of ZPT2-3 transcript, and the activity of ZPT2-3::luciferase was
      conferred by the 1668-bp ZPT2-3 upstream sequence, both locally and systemically.
      This induction was mediated by a jasmonic acid (JA)-dependent and ethylene
      independent pathway. ZPT2-3 expression was also induced by cold, drought, and
      heavy metal treatments. The same ZPT2-3 promoter sequence showed similar
      responsiveness to wounding, cold, drought, and JA treatments in Arabidopsis when
      investigated in a beta-glucuronidase (GUS) reporter gene, indicating conservation
      of similar signaling pathways between the two plant species. ZPT2-3 functioned as
      an active repressor in a transient assay using Arabidopsis leaves. Constitutive
      overexpression of ZPT2-3 in transgenic petunia plants increased tolerance to
      dehydration. These results demonstrate the involvement of ZPT2-3 in plant
      response to various stresses, and suggest its potential utility to improve
      drought tolerance.

PMID- 14675449
TI  - CSP41a, a multifunctional RNA-binding protein, initiates mRNA turnover in tobacco
      chloroplasts.
AB  - Expression of chloroplast stem-loop binding protein (CSP)41a, a highly conserved
      chloroplast endoribonuclease, was reduced >90% by the expression of antisense RNA
      in Nicotiana tabacum. The most striking effects of this silencing were two- to
      sevenfold decreases in the degradation rates of rbcL, psbA, and petD transcripts
      in lysed chloroplast extracts. These results are consistent with the hypothesis
      that CSP41a participates in initiating mRNA turnover through endonucleolytic
      cleavages. Surprisingly, rbcL and psbA mRNAs accumulated to similar levels in
      wild-type and antisense lines. This suggested that decreased degradation was
      compensated by reduced transcription, which was confirmed using run-on
      transcription assays. The collective accumulation of petD-containing mRNAs in
      antisense plants decreased by 25% compared to wild-type controls. However, the
      relative levels of petD processing intermediates in wild-type and antisense
      plants did not differ, and there were no changes in petD 3'-end maturation,
      suggesting that CSP41a is not required for petD RNA processing. CSP41a is a Mg2+
      dependent enzyme; therefore, extracts from antisense plants were tested at
      different Mg2+ concentrations. These experiments showed that the half-life of
      rbcL decreased as the Mg2+ concentration was reduced, and at <1 mm free Mg2+,
      conditions where CSP41a is nearly inactive in vitro, the rbcL degradation rate
      was similar in wild-type and antisense extracts, suggesting that CSP41a is
      normally bypassed under these conditions. Mg2+ has been shown to mediate RNA
      stability during chloroplast biogenesis, and our data suggest that regulation of
      CSP41a activity by Mg2+ is a component of this process.

PMID- 14675450
TI  - The NOMEGA gene required for female gametophyte development encodes the putative
      APC6/CDC16 component of the Anaphase Promoting Complex in Arabidopsis.
AB  - Development of the female gametophyte involves several rounds of nuclear
      divisions during which nuclei are rearranged and finally cellularized to form a
      mature seven-celled embryo sac. During these nuclear divisions, key proteins
      involved in the cell cycle need to be degraded quickly in order to facilitate
      both the metaphase-anaphase transition stage and late anaphase. Here, we report
      the characterization of an Arabidopsis mutant nomega, which results in arrest of
      the embryo sac development at the two-nucleate stage. The NOMEGA gene product
      shows high homology to the APC6/cell division cycle (CDC)16 subunit of the
      Anaphase Promoting Complex/Cyclosome (APC/C). The phenotype of the nomega mutant
      is quite different from that of the hobbit mutant, which had suggested a role for
      the plant APC/C in auxin signalling. We show that nomega mutant embryo sacs are
      unable to degrade Cyclin B, an important APC/C substrate, providing further
      evidence of a role for the NOMEGA gene product and the plant APC/C in cell cycle
      progression during gametophyte development.

PMID- 14675451
TI  - An ancient R gene from the wild potato species Solanum bulbocastanum confers
      broad-spectrum resistance to Phytophthora infestans in cultivated potato and
      tomato.
AB  - Late blight, caused by the oomycete pathogen Phytophthora infestans, is the most
      devastating disease for potato cultivation. Here, we describe the positional
      cloning of the Rpi-blb1 gene from the wild potato species Solanum bulbocastanum
      known for its high levels of resistance to late blight. The Rpi-blb1 locus, which
      confers full resistance to complex isolates of P. infestans and for which race
      specificity has not yet been demonstrated, was mapped in an intraspecific S.
      bulbocastanum population on chromosome 8, 0.3 cM from marker CT88. Molecular
      analysis of a bacterial artificial chromosome (BAC) clone spanning the Rpi-blb1
      locus identified a cluster of four candidate resistance gene analogues of the
      coiled coil, nucleotide-binding site, leucine-rich repeat (CC-NBS-LRR) class of
      plant resistance (R) genes. One of these candidate genes, designated the Rpi-blb1
      gene, was able to complement the susceptible phenotype in a S. tuberosum and
      tomato background, demonstrating the potential of interspecific transfer of broad
      spectrum late blight resistance to cultivated Solanaceae from sexually
      incompatible host species. Paired comparisons of synonymous and non-synonymous
      nucleotide substitutions between different regions of Rpi-blb1 paralogues
      revealed high levels of synonymous divergence, also in the LRR region. Although
      amino acid diversity between Rpi-blb1 homologues is centred on the putative
      solvent exposed residues of the LRRs, the majority of nucleotide differences in
      this region have not resulted in an amino acid change, suggesting conservation of
      function. These data suggest that Rpi-blb1 is relatively old and may be subject
      to balancing selection.

PMID- 14675452
TI  - Nuclear localization and in vivo dynamics of a plant-specific serine/arginine
      rich protein.
AB  - Serine/arginine-rich (SR) proteins in non-plant systems are known to play
      important roles in both constitutive and alternative splicing of pre-messenger
      RNAs (pre-mRNAs). Recently, we isolated a novel SR protein (SR45), which
      interacts with U1 snRNP 70K protein, a key protein involved in 5' splice site
      recognition. SR45 is found only in plants and is unique in having two SR domains
      separated by an RNA recognition motif (RRM). To study the localization and
      dynamics of SR45, we expressed it as a fusion to green fluorescent protein (GFP)
      in cultured cells and transgenic Arabidopsis plants. The SR45 is localized
      exclusively to nuclei. In interphase nuclei, GFP-SR45 was found both in speckles
      and nucleoplasm. The speckles exhibited intranuclear movements and changes in
      morphology. Inhibition of transcription and protein phosphorylation resulted in
      redistribution of SR45 to bigger speckles. The change in the number and
      morphology of speckles caused by inhibition of transcription was blocked by an
      inhibitor of phosphatases. These results indicate that transcription activity of
      the cell and protein (de)phosphorylation regulate the intranuclear distribution
      of SR45.

PMID- 14675453
TI  - KINKY POLLEN encodes a SABRE-like protein required for tip growth in Arabidopsis
      and conserved among eukaryotes.
AB  - In higher plants, pollen tubes and root hairs share an ancient growth process
      named tip growth. We have isolated three allelic Arabidopsis mutant lines showing
      kinky-shaped pollen tubes and, when homozygous, showing shorter and thicker root
      hairs. The ultrastructure of pollen tubes in these kinky pollen (kip) mutants is
      similar to that of the wild type; however, time-lapse studies suggest that
      aberrant pollen tube shape is caused by periodic growth arrests alternated with
      phases of tube axis reorientation. The KIP gene encodes a protein of 2587 amino
      acids that is predicted to be targeted to the secretory pathway. KIP mRNA was
      detected in all organs investigated but was most abundant in pollen and roots.
      KIP has putative homologues in many eukaryotes, including mammals and yeast, and
      is similar to the Arabidopsis SABRE gene, whose mutation causes a dwarf
      phenotype. The phenotype of the kip/sab double mutant suggests related functions
      for both genes, however, the KIP protein is mostly required for tip-growth.

PMID- 14675454
TI  - Two MAPK cascades, NPR1, and TGA transcription factors play a role in Pto
      mediated disease resistance in tomato.
AB  - The tomato Pto kinase confers resistance to the causative agent of bacterial
      speck disease, Pseudomonas syringae pv. tomato, by recognizing the pathogen
      effector proteins AvrPto or AvrPtoB. Pto-mediated resistance requires multiple
      signal transduction pathways and has been shown to activate many defense
      responses including an oxidative burst, rapid changes in the expression of over
      400 genes, and localized cell death. We have tested the role in Pto-mediated
      resistance in tomato of a set of 21 genes from other species known to be involved
      in defense-related signaling. Expression of each gene was suppressed by virus
      induced gene silencing (VIGS) and the effect on disease symptoms and bacterial
      growth during the tomato-Pseudomonas incompatible interaction was determined. We
      found that Pto-mediated resistance was compromised by silencing of genes encoding
      two mitogen-activated protein (MAP) kinase kinases, MEK1 and MEK2, two MAP
      kinases, NTF6 and wound-induced protein kinase (WIPK), a key regulator of
      systemic acquired resistance (SAR), NPR1, and two transcription factors, TGA1a
      and TGA2.2. A lesser impact on Pto-mediated resistance was observed in plants
      silenced for RAR1 and COI1. The identification of nine genes that play a role in
      resistance to bacterial speck disease both advances our knowledge of Pto signal
      transduction and demonstrates the conservation of many defense signaling
      components among diverse plant species.

PMID- 14675455
TI  - The ethanol switch: a tool for tissue-specific gene induction during plant
      development.
AB  - Controlled gene expression in time and space is a powerful tool for the analysis
      of gene function during plant development. Here, we report ethanol inducible gene
      expression in defined sub-domains of the shoot apical and floral meristems. For
      this, expression of an ethanol-regulated transcription factor, ALCR, is
      restricted to precise domains using specific promoters. Gene expression
      activation is followed using reporters under the control of the alcA promoter,
      which responds to ALCR only in the presence of the ethanol. We demonstrate that
      precise control of spatially limited gene expression can be achieved. The
      kinetics of reporter gene activation and inactivation following a pulse of
      ethanol induction shows that the system is dynamic and suitable for precise
      temporal control of expression. The system is both flexible and robust,
      permitting simultaneous expression of two genes in a given domain or, conversely,
      the expression of a gene in two separate domains. We also show that this strategy
      can be applied to mis-express genes with developmental roles, by manipulating
      expression of the SHOOT MERISTEMLESS (STM) and CYCLIN D3;1 (CYCD3;1) genes during
      plant development.

PMID- 14675456
TI  - Isolation of AtSUC2 promoter-GFP-marked companion cells for patch-clamp studies
      and expression profiling.
AB  - K+ channels control K+ homeostasis and the membrane potential in the sieve
      element/companion cell complexes. K+ channels from Arabidopsis phloem cells
      expressing green fluorescent protein (GFP) under the control of the AtSUC2
      promoter were analysed using the patch-clamp technique and quantitative RT-PCR.
      Single green fluorescent protoplasts were selected after being isolated
      enzymatically from vascular strands of rosette leaves. Companion cell
      protoplasts, which could be recognized by their nucleus, vacuole and
      chloroplasts, and by their expression of the phloem-specific marker genes SUC2
      and AHA3, formed the basis for a cell-specific cDNA library and expressed
      sequence tag (EST) collection. Although we used primers for all members of the
      Shaker K+ channel family, we identified only AKT2, KAT1 and KCO6 transcripts. In
      addition, we also detected transcripts for AtPP2CA, a protein phosphatase, that
      interacts with AKT2/3. In line with the presence of the K+ channel transcripts,
      patch-clamp experiments identified distinct K+ channel types. Time-dependent
      inward rectifying K+ currents were activated upon hyperpolarization and were
      characterized by a pronounced Ca2+-sensitivity and inhibition by protons. Whole
      cell inward currents were carried by single K+-selective channels with a unitary
      conductance of approximately 4 pS. Outward rectifying K+ channels (approximately
      19 pS), with sigmoidal activation kinetics, were elicited upon depolarization.
      These two dominant phloem K+ channel types provide a versatile mechanism to
      mediate K+ fluxes required for phloem action and potassium cycling.

PMID- 14675457
TI  - Progress in methodology. Improved reporter gene assays used to identify ligands
      acting on orphan seven-transmembrane receptors.
AB  - Seven-transmembrane G-protein-coupled receptors play a central role in physiology
      by facilitating cell communication through recognition of a wide range of
      ligands. Even more important, they represent important drug targets.
      Unfortunately, for many of these receptors the endogenous ligands, and hence
      their functions, remain to be identified. These receptors are referred to as
      "orphan" receptors. A pre-requisite for the identification of ligands activating
      orphan receptors is powerful assay systems. Until now, reporter gene assays have
      not been in common use in this process. Here, we summarize our development of
      improved reporter gene assays. We optimized reporter gene assays in respect of
      (i) the promoter region of the construct, (ii) the reporter enzyme used, (iii)
      and the assay procedure. Furthermore, an unique fluorescence-based clone
      selection step was introduced, allowing rapid selection of the most sensitive
      reporter cell clones when establishing stable reporter cell lines. Mathematical
      formulae are provided to enable a simple and reliable comparison between
      different cell lines, when tested with a compound of interest. The resulting
      reporter cell lines responded in a very sensitive way to the stimulation of
      various test receptors. The reporter system was termed HighTRACE (high-throughput
      reporter assay with clone election). Its high assay quality makes it suitable as
      a primary screening tool. Ligands for two recently unknown 7TM receptors were
      identified using the HighTRACE system i.e., two cell surface free fatty acid
      receptors, GPR40 (FFA1R) and GPR43 (FFA2R). The identification was accomplished
      using a reverse pharmacology approach.

PMID- 14675458
TI  - Induction of NAD(P)H:quinone reductase by probucol: a possible mechanism for
      protection against chemical carcinogenesis and toxicity.
AB  - Dietary antioxidants protect laboratory animals against induction of tumours by a
      variety of chemical carcinogens. Among possible mechanism, protection against
      chemical carcinogenesis could be mediated via antioxidant-dependent induction of
      detoxifying enzymes, including quinone reductase and glutathione S-transferase
      (GSH transferase). Probucol is used cholesterol-lowering drug used in the clinic,
      with pronounced antioxidant effect that protect against chemical carcinogenesis
      and toxicity. In the present study we therefore examined the ability of probucol
      to induce activities of quinone reductase in the cytosolic fractions of various
      tissues of mice. Quinone reductase activity was increased significantly in 6 of 8
      tissues examined from probucol-fed mice. The greatest proportionate increase, to
      1.8 times control levels, was observed in liver. Probucol also increased quinone
      reductase activities of forestomach, heart, kidney, lungs and spleen. Quinone
      reductase is a major enzyme of xenobiotic metabolism that carries out obligatory
      two-electron reductions and thereby protects cells against toxicity of quinones.
      It is induced in many tissues coordinately with other enzymes that protect
      against electrophilic toxicity. The protective effects of probucol appear to be
      due, at least in part, to the ability of this antioxidant to increase the
      activities in rodent tissues of several enzymes involved in the non-oxidative
      metabolism of a wide variety of xenobiotics. The induction of such enzyme,
      quinone reductase by probucol suggests the potential value of this compound as a
      protective agent against chemical carcinogenesis and other forms of electrophilic
      toxicity. The significance of these results can be implicated in relation to
      cancer chemopreventive effects of probucol in various target organs.

PMID- 14675459
TI  - 6-Ethyl-N,N'-bis(3-hydroxyphenyl)[1,3,5]triazine-2,4-diamine (RS-0466) enhances
      the protective effect of brain-derived neurotrophic factor on amyloid beta
      induced cytotoxicity in cortical neurones.
AB  - Amyloid beta peptide in the senile plaques of patients with Alzheimer's disease
      is considered to be responsible for the pathology of Alzheimer's disease. We have
      previously reported that 6-ethyl-N,N'-bis(3-hydroxyphenyl)[1,3,5]triazine-2,4
      diamine, RS-0466, is capable of significantly inhibiting amyloid beta-induced
      cytotoxicity in HeLa cells. To determine various profiles of RS-0466, we
      investigated whether RS-0466 would enhance the neuroprotective effect of brain
      derived neurotrophic factor on amyloid beta(1-42)-induced cytotoxicity in rat
      cortical neurones. Consistent with previous observations, brain-derived
      neurotrophic factor ameliorated amyloid beta(1-42)-induced cytotoxicity.
      Furthermore, co-application of RS-0466 enhanced the neuroprotective effect of
      brain-derived neurotrophic factor. RS-0466 also reversed amyloid beta(1-42)
      induced decrease of brain-derived neurotrophic factor-triggered phosphorylated
      Akt. These results raise the possibility that RS-0466 or one of its derivatives
      has potential to enhance the neuroprotective effect of brain-derived neurotrophic
      factor, and could serve as a therapeutic agent for patients with Alzheimer's
      disease.

PMID- 14675460
TI  - Mepivacaine alters vascular responsiveness to vasoconstrictors in aortic rings
      from normal and aortic-banded rats.
AB  - The present study investigated the effects of mepivacaine on the response of rat
      aorta to vasoconstrictors in normal and aortic-banded animals. Cardiac
      hypertrophy was induced in Wistar rats by aortic banding, while sham-operated
      animals served as controls. Isolated aortic rings with or without endothelium
      were contracted with potassium chloride and phenylephrine in the presence of
      mepivacaine (10(-3) M). Maximal tension was measured at the highest concentration
      of potassium chloride and phenylephrine. Maximal response to potassium chloride
      was reduced in the presence of mepivacaine both in normal and aortic-banded
      rings. As regards the vascular reactivity to phenylephrine, aortic rings with
      intact endothelium from aortic-banded rats have shown increased response as
      compared to normal. After mepivacaine administration this difference between
      normal and aortic-banded rats was abolished. In conclusion, in a model of cardiac
      hypertrophy such as that of aortic-banding, increased response to alpha1
      adrenergic stimulation is observed, which is blunted by mepivacaine
      administration.

PMID- 14675461
TI  - In vitro induction of differentiation by ginsenoside Rh2 in SMMC-7721
      hepatocarcinoma cell line.
AB  - The aim of this study was to investigate the effects of ginsenoside Rh(2) (G
      Rh(2)) on differentiation of SMMC-7721 hepatocarcinoma cell line in culture. We
      studied G-Rh(2)-induced differentiation of SMMC-7721 cells through cell
      proliferation, cell morphology, ultrastructure, cell cycle, cell function and
      metabolism. The proliferation of treated cells was inhibited, the morphology and
      ultrastructure seemed normal, the secretory amount and expression of alpha
      foetoprotein, and the specific activity of gamma-glutamyl transpeptidase, and
      heat-resistant alkaline phosphatase were all significantly decreased, the
      secretory amount of albumin and alkaline phosphatase activity were remarkably
      increased, and the cell was arrested at the G(1)/G(0) phase. Furthermore, G-Rh(2)
      induced elevated expression of the cyclin-dependent kinase inhibitor p21(WAF1)
      and p16(INK4a), and declined expressions of cyclin D1 and cyclin E. In addition,
      G-Rh(2) almost completely inhibited telomerase activity, as measured by
      polymerase chain reaction-based telomeric repeat amplification protocol coupled
      with enzyme-linked immune sorbent assay, and human telomerase reverse
      transcriptase mRNA. Based on these data, it is suggested that G-Rh(2) could
      induce cell differentiation tending to normal and effectively reduce telomerase
      activity with affecting transcription levels of human telomerase reverse
      transcriptase, paralleling the induction of cell differentiation.

PMID- 14675462
TI  - Inhibition by uric acid of free radicals that damage biological molecules.
AB  - To clarify the antioxidative role of uric acid, its ability to scavenge carbon
      centered and peroxyl radicals and its inhibitory effect on lipid peroxidation
      induced by various model systems were examined. Uric acid efficiently scavenged
      carbon-centered and peroxyl radicals derived from the hydrophilic free radical
      generator 2,2'-azobis-(2-amidinopropane)-dihydrochloride (AAPH). All damage to
      biological molecules, including protein, DNA and lipids induced by AAPH, was
      strongly prevented by uric acid. In contrast, alpha-tocopherol had little effect
      on damage to biological molecules. Lipid peroxidation by the lipophilic free
      radical generator 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) was little
      inhibited by uric acid, but not by alpha-tocopherol. Copper-induced lipid
      peroxidation was inhibited by uric acid and alpha-tocopherol. NADPH- and ADP
      Fe(3+)-dependent microsomal lipid peroxidation was efficiently inhibited by alpha
      tocopherol, but not by uric acid. Uric acid seems to scavenge free radicals in
      hydrophilic conditions to inhibit lipid peroxidation on the lipid-aqueous
      boundary, and the antioxidation is only little in lipophilic conditions.

PMID- 14675463
TI  - Melatonin protects against mercury(II)-induced oxidative tissue damage in rats.
AB  - Mercury exerts a variety of toxic effects in the body. Lipid peroxidation, DNA
      damage and depletion of reduced glutathione by Hg(II) suggest an oxidative stress
      like mechanism for Hg(II) toxicity. Melatonin, the main secretory product of the
      pineal gland, was recently found to be a potent free radical scavenger and
      antioxidant. N-Acetylcysteine, a precursor of reduced glutathione and an
      antioxidant, is used in the therapy of acute heavy metal poisoning. In this study
      the protective effects of melatonin in comparison to that of N-acetylcysteine
      against Hg-induced oxidative damage in the kidney, liver, lung and brain tissues
      were investigated. Wistar albino rats of either sex (200-250 g) were divided into
      six groups, each consisting of 8 animals. Rats were intraperitoneally injected
      with 1) 0.9% NaCl, control (C) group; 2) a single dose of 5 mg/kg mercuric
      chloride (HgCl2), Hg group; 3) melatonin in a dose of 10 mg/kg, 1 hr after HgCl2
      injection, Hg-melatonin group; 4) melatonin in a dose of 10 mg/kg one day before
      and 1 hr after HgCl2 injection, melatonin-Hg-melatonin group; 5) N-acetylcysteine
      in a dose of 150 mg/kg, 1 hr after HgCl2 injection, Hg-N-acetylcysteine group,
      and 6) N-acetylcysteine in a dose of 150 mg/kg one day before and 1 hr after
      HgCl2 injection, N-acetylcysteine-Hg-N-acetylcysteine group. Animals were killed
      by decapitation 24 hr after the injection of HgCl2. Tissue samples were taken for
      determination of malondialdehyde, an end-product of lipid peroxidation;
      glutathione (GSH), a key antioxidant, and myeloperoxidase activity, an index of
      neutrophil infiltration. The results revealed that HgCl2 induced oxidative tissue
      damage, as evidenced by increases in malondialdehyde levels. Myeloperoxidase
      activity was also increased, and GSH levels were decreased in the liver, kidney
      and the lungs. All of these effects were reversed by melatonin or N
      acetylcysteine treatment. Since melatonin or N-acetylcysteine administration
      reversed these responses, it seems likely that melatonin or N-acetylcysteine can
      protect all these tissues against HgCl2-induced oxidative damage.

PMID- 14675464
TI  - Spontaneous reversal of p-glycoprotein expression in multidrug resistant cell
      lines.
AB  - Increased expression of P-glycoprotein encoded by the mdr-1 gene is a well
      characterised mechanism for resistance to cancer chemotherapeutic drugs in cell
      lines. However, the P-glycoprotein expression after removal of the selection
      pressure has not fully been elucidated. The stability of P-glycoprotein
      expression in the presence (+) and absence (-) of vincristine (30 or 150 nM) was
      studied in multidrug resistant K562 cell lines (VCR30+, VCR150+, VCR30- and
      VCR150-) for 11 months. The P-glycoprotein protein and mdr-1 mRNA levels were
      determined at regular intervals using flow cytometry and real-time PCR,
      respectively. Chemosensitivity to a panel of antineoplastic drugs was measured
      using an MTT assay. The presence of vincristine (VCR30+ and VCR150+) resulted in
      high and stable levels of P-glycoprotein and mdr-1 mRNA during the whole period
      compared to wild type. As for the VCR30- and VCR150- subcultures, the expressions
      of P-glycoprotein and mdr-1 mRNA were stable for five months, and then the levels
      decreased rapidly. Concomitantly, the sensitivity to drugs known as P
      glycoprotein substrates was restored. In conclusion, resistant cells growing in
      the presence of the inducing drug have a stable P-glycoprotein expression and
      resistance level, but removing the inducing drug may result in a sudden and rapid
      lowering of P-glycoprotein and mdr-1 mRNA levels as long as five months after
      drug withdrawal.

PMID- 14675467
TI  - Kiwi fruit allergy: a review.
AB  - Allergy to kiwi fruit was first described in 1981, and there have since been
      reports of the allergy presenting with a wide range of symptoms from localized
      oral allergy syndrome (OAS) to life-threatening anaphylaxis. The article reviews
      the available information concerning the clinical features of kiwi fruit allergy
      and the role of clinical investigations for diagnosis. Work identifying the major
      allergens in kiwi fruit has resulted in conflicting results, the possible reasons
      for which are discussed. The clinical associations of kiwi fruit allergy with
      allergies to pollens or latex are reviewed.

PMID- 14675468
TI  - Evaluation of clinical and immunological effects of inactivated influenza vaccine
      in children with asthma.
AB  - Although annual influenza vaccinations are recommended by many authorities, some
      doctors may be reluctant to vaccinate asthmatic children because of the risk of
      inducing bronchial reactivity and exacerbating the asthma. In this study, the
      effect of split influenza vaccine on clinical symptoms, airway responsiveness and
      its influence on T lymphocytes was evaluated. Twenty-one asthmatic children with
      stable asthma were recruited and divided into two groups. Eleven patients who
      received the influenza vaccine formed the vaccination group and 10 patients who
      received a placebo formed the placebo group. Forced expiratory volume in 1 s
      (FEV1), airway response (PC20 methacholine, PC20=provocation concentration
      causing a 20% fall in FEV1) and the T lymphocyte subset ratio (Th1/Th2) were
      recorded on day 1 pre-vaccination and day 14 post-vaccination. Patients were also
      asked to record their peak expiratory flow (PEF) every morning and evening and to
      complete daily symptom scores over the period of 2 weeks. There were no
      significant changes in PC20, FEV1, PEF variability, symptom scores and the
      Th1/Th2 ratio between the vaccination and placebo groups between day 1 pre
      vaccination and day 14 post-vaccination. Similar results of PEF variability and
      asthma symptom score were obtained when the analysis was restricted to the day 1
      pre-vaccination and day 3 post-vaccination. Immunization with split influenza
      vaccine does not exacerbate asthma in children either with a clinical or
      immunological effect. These results suggest that children with stable asthma can
      safely be immunized with a split influenza vaccine.

PMID- 14675469
TI  - Respiratory syncytial virus augments production of fibroblast growth factor basic
      in vitro: implications for a possible mechanism of prolonged wheezing after
      infection.
AB  - Respiratory syncytial virus (RSV) has been linked to the development of clinical
      asthma. Cellular mechanisms of this observation are not yet clearly elucidated.
      In chronic asthma, production of growth factors and remodeling are associated
      with prolonged wheezing. It was hypothesized that cells infected with RSV may
      produce excessive levels of fibroblast growth factor basic (FGFb), and epidermal
      growth factor (EGF). Airway epithelial cells were incubated with either: (i)
      virus, (ii) inactivated virus, or (iii) media only. The levels of FGFb and EGF
      were measured in the cellular supernatant fluid. The study demonstrated that by
      24 h after RSV inoculation, or exposure to RSV-killed virus, cells are stimulated
      to produce significantly more FGFb, compared with non-infected/non-exposed
      control cells. FGFb is an important factor in remodeling and fibroblast
      activation in the airway. Using treatment with actinomycin D and cylcohexamide
      the effect of inhibiting translation or transcription in the infected cells, on
      FGFb production was demonstrated. There were no alterations in EGF production
      detectable. Based on the findings, the mechanism of FGFb secretion after RSV
      inoculation, appears to be regulated at the levels of both transcription and
      translation. The increased FGFb release potentially could contribute to
      fibroblast activation and remodeling in the airway, and thus provide another
      possible mechanism for prolonged wheezing after infection.

PMID- 14675470
TI  - Quantification of IgE antibodies simplifies the classification of allergic
      diseases in 4-year-old children. A report from the prospective birth cohort study
      -BAMSE.
AB  - Allergic diseases are common among small children, but it is still unclear how
      immunoglobulin E (IgE) antibodies to ambient allergens are distributed in a
      population-based prospective material of children at 4 years of age. The study is
      based on 75% (n = 4089) of all eligible children from northern Stockholm, born
      between 1994 and 1996 in pre-defined geographical areas. Data on exposure and
      outcome were obtained by parental questionnaires when the child was 3 months and
      4 years of age. Of the 92% who responded to the 4 years of age questionnaire,
      serum was obtained in 88% of these children for analysis of IgE antibodies
      performed with Pharmacia CAP system (Phadiatop and food mix fx5). An antibody
      level > or =0.35 kUA/l was considered as positive. A positive Phadiatop or fx5
      was found in 24% of the 4 years old children. A rather poor correlation was found
      between the two tests (r = 0.39). Occurrence of IgE antibodies > or =3.5 kU/l for
      both Phadiatop and fx5 in combination could predict any suspected allergic
      disease [asthma, rhinitis, atopic eczema dermatitis syndrome (AEDS) and allergic
      reaction to food] to 97.4%. However, the presence of > or =3.5 kUA/l of Phadiatop
      or fx5 used as single tests only, was far less efficient to predict any allergic
      disease. The two mixes of airborne and food allergens were also associated, not
      only to the severity of the allergic disease in terms of number of organ
      involved, but also to the severity of recurrent wheeze, in particular in boys
      with a positive Phadiatop who exhibited significantly limited peak flows compared
      to those with a negative test. Already at the age of 4, one child in four is
      sensitized to an allergen as assessed by Phadiatop or food mix (fx5). The
      presence of IgE antibodies seems not only to predict allergic diseases in this
      age group, but also relates to severity of such diseases, in particular to
      asthma. Notable, there was a poor correlation between Phadiatop and fx5 that
      needs to be considered when identifying allergic diseases in young children. The
      study demonstrates that quantification of IgE antibodies in blood may be
      beneficial, not only to diagnose allergic diseases in young children, but
      especially to serve as a marker of severity of asthma.

PMID- 14675471
TI  - Sensitization to food and airborne allergens in children with atopic dermatitis
      followed up to 7 years of age.
AB  - Previously we investigated the eczema prognosis and the risk of developing
      allergic asthma and rhinitis in a cohort of 94 children with atopic dermatitis.
      In this second study on the same cohort we address the development of
      sensitization to foods and airborne allergens, risk factors and, the question
      whether children with atopic dermatitis who will not become sensitized can be
      recognized early. Children with atopic dermatitis were followed up regularly from
      infancy or early childhood to 7 years of age with clinical examination and blood
      sampling. After age 3, skin prick tests with inhalation allergens were performed
      yearly. In most children both clinical allergy and sensitization to egg and milk
      were transient but those to peanut were persistent. Eighty per cent of the
      children became sensitized to airborne allergens and 75% of them noticed symptoms
      when exposed. Heredity for atopy and eczema, sensitization to hen's egg, and
      early onset of eczema entailed an increased risk of becoming sensitized. Children
      never sensitized had late onset of eczema and less heredity for atopic disease
      but did not differ in other respects from the sensitized children.

PMID- 14675472
TI  - Clinical and therapeutic aspects of allergic asthma in adolescents.
AB  - Little is known about the management of asthma in adolescents. We aimed at
      evaluating these aspects, through a specific questionnaire, in the real life of
      adolescents with allergic asthma. The questionnaire was administered to a group
      of adolescents after a diagnosis of allergic asthma. The diagnosis was based on
      history, clinical examination, pulmonary function tests and allergy tests. One
      hundred and fifteen adolescents (65 males, mean age 16.5 years) fulfilled the
      criteria for allergic asthma. The questionnaire explored demography, family
      history, clinical history, previous diagnosis, therapy, attitude towards therapy
      and social aspects. The mean actual FEV1 was 87 +/- 10%. Methacholine challenge
      was carried out in 79 patients and was always positive (PD20 < 1,200 microg),
      whereas 36 patients underwent reversibility test. According to GINA guidelines,
      severity of asthma resulted intermittent in 62, mild persistent in 31, moderate
      in 19 and severe in three patients. In 61% of cases teachers were not aware of
      the disease. Asthma was managed by general practitioners, allergists and
      pulmonologists, but PFT/allergy tests had never been performed in 14% of
      patients. Forty-two per cent of the adolescents received no therapy at all, and
      only 15% of those with persistent asthma were receiving a stable treatment.
      Seventy-four per cent of adolescents preferred the inhaled, as against the oral,
      route. From a clinical and functional point of view, asthma in adolescents did
      not differ from other age ranges. Nevertheless, the management (diagnosis and
      therapy) emerged to be unsatisfactory from many points of view.

PMID- 14675473
TI  - Non-specific bronchial hyper-responsiveness in children with allergic rhinitis:
      relationship with the atopic status.
AB  - An increased prevalence of bronchial hyper-responsiveness (BHR) has been
      demonstrated in children from a general population, and in non-asthmatic adults
      with allergic rhinitis. Thus, also children with allergic rhinitis are expected
      to be at higher risk of BHR. We evaluated the prevalence of BHR in a sample of
      non-asthmatic children with allergic rhinitis by means of the methacholine (Mch)
      bronchial challenge, and by monitorizing the airway patency using the daily peak
      expiratory flow variability (PEFv). Fifty-one children (ranged 6-15 years of age)
      with allergic rhinitis, ascertained by skin prick test to inhalant allergens,
      underwent a 14-day peak expiratory flow monitoring, and a Mch bronchial
      provocation challenge. Thirty healthy children matched for age, and sex served as
      control group. Thirty-one children in the rhinitis group (61%), and six (20%) in
      the control group were Mch+ (Mch provocative dose causing a 20% fall of forced
      expiratory volume in 1 s respect to baseline <2250 microg, equivalent to 11.50
      micromol). In rhinitic children the PEFv did not significantly differ between
      Mch+ and Mch- subjects, but the total serum immunoglobulin E (IgE) were higher
      among Mch+. The persistent form of rhinitis was significantly associated to Mch
      positivity. Non-asthmatic children with allergic rhinitis displayed a high
      prevalence of BHR. The BHR was significantly associated with persistent rhinitis
      and with higher total IgE levels. Nevertheless, the spontaneous changes in airway
      patency, as expressed by PEFv, were within normal limits both in Mch+ and Mch-
      children.

PMID- 14675474
TI  - Birth order and sibship size as independent risk factors for asthma, allergy, and
      eczema.
AB  - This study was carried out to disentangle the independent relations of birth
      order and sibship size with the presence of asthma, allergy and eczema. In a
      retrospective study, 700 families in the Netherlands were selected with index
      children born in 1988-90. Data were extracted from reports of health examinations
      at the age of 6 years of these children and their siblings. Birth order, and not
      sibship size, appeared to be a strong risk factor for allergy (excluding eczema).
      Children with higher birth order had a lower risk of allergy compared with first
      borns (adjusted odds ratios: 0.43, 0.26 and 0.05 for second-, third- and fourth-
      or higher borns, respectively; p < 0.0001). Allergy including eczema also had a
      significant relation with birth order (p = 0.01). For asthma there appeared no
      clear relation with birth order. For asthma a non-significant relationship with
      sibship size (adjusted for birth order) was found (p = 0.06): first-born children
      in small sibships were more at risk than those in larger sibships. For allergy
      and eczema no such trend was observed. In conclusion, birth order is inversely
      related to the risk of allergy, independent of the size of the sibship.

PMID- 14675475
TI  - Maternal atopy and the number of offspring: is there an association?
AB  - We investigated the association between maternal atopy and the number of
      offspring. In a population- and pregnancy-based survey (part of the European
      Studies on Infertility and Subfecundity), we obtained information on the number
      of offspring, adverse pregnancy outcomes, age at pregnancy, and waiting time to
      pregnancy. The German portion of these surveys also included information on
      physician-diagnosis of asthma, atopic eczema, or hay fever. The odds ratio (OR)
      adjusted for age showed that the number of children was reduced among women with
      atopy (OR = 0.75, 95% CI: 0.57-0.98 in the pregnancy-based sample; OR = 0.79, 95%
      CI: 0.63-0.99 in the population-based sample). We did not identify other signs of
      reduced reproductive ability in atopic women. The results provide support for two
      assumptions: (i) either a lower number of offspring in atopic mothers combined
      with an increased risk of atopy in offspring of atopic mothers may explain the
      protective effect of a higher number of siblings on atopy in offspring; or (ii)
      successive pregnancies may decrease the atopic response of the mother and thus
      the risk of developing atopy in subsequent offspring.

PMID- 14675476
TI  - Total and allergen-specific IgE levels in serum reflect blood eosinophilia and
      fractional exhaled nitric oxide concentrations but not pulmonary functions in
      allergic asthmatic children sensitized to house dust mites.
AB  - Although elevated levels of serum immunoglobulin E (IgE) are considered the
      hallmark of atopic diseases, their clinical value in evaluating subjects with
      allergic disorders is under debate. To evaluate possible relationships between
      serum IgE levels and a variety of clinical parameters, 83 mild asthmatic children
      [10.98-year-old (2.95)], sensitized to house dust mites (HDM) Dermatophagoides
      pteronyssinus (Dp) or D. farinae (Df), were enrolled. As compared with normal
      control reference values detected in our laboratory, children with allergic
      asthma had higher blood eosinophil counts (expressed both as percentage and as
      absolute number) and higher fractional exhaled nitric oxide (FeNO) levels but
      similar values in pulmonary function parameters. In the allergic asthmatic
      population, serum levels of total, Dp-specific or Df-specific IgE correlated
      positively with eosinophil counts (Rho > or = 0.30, p < 0.01, each correlation)
      and FeNO levels (Rho > or = 0.33, p < 0.01, each correlation) but not with
      pulmonary function parameters (p > 0.1, each correlation). Finally, significant
      correlations, although moderate, were found in the allergic asthmatic population
      between eosinophil counts and FeNO levels (Rho > or = 0.42, p < 0.001, each
      correlation). Thus, in atopic children sensitized to HDM with mild intermittent
      asthma, IgE levels in blood appear to reflect systemic (blood eosinophils) and
      organ-specific (FeNO) markers of allergic inflammation but not pulmonary volumes
      or the degree of airflow limitation.

PMID- 14675477
TI  - Cutaneous reactions to pine processionary caterpillar (Thaumetopoea pityocampa)
      in pediatric population.
AB  - Cutaneous lesions caused by pine processionary caterpillar (Thaumetopoea
      pityocampa, TP) are frequent in pinewood areas. However, no epidemiological
      studies have been performed so far in the pediatric population. In this study, we
      evaluated the relevance of reactions to pine processionary caterpillar in the
      pediatric population of our environment and determined the possible role of an
      IgE-mediated mechanism. A questionnaire was developed and given to 1,101 children
      and adolescents ranging from 3 to 17 years of age from rural areas with large
      pine forests. A total of 653 questionnaires were answered by the children or
      their parents. The search for immunoglobulin E (IgE)-mediated cases was based on
      the presence of a suspected reaction to caterpillar and confirmed by in vivo
      (skin prick) and in vitro (immunoblotting) tests. Sixty of the 653 people
      interviewed (9.18%) identified a cutaneous reaction from exposure to the
      processionary caterpillar. Within this group only four cases (6.7%) were because
      of an IgE-mediated mechanism. The predominant clinical feature of these patients
      with allergy to caterpillar was contact urticaria. We present the first study of
      cutaneous reactions to pine processionary caterpillar in a large pediatric
      population. This is a frequent pathology in pinery zones and only in a minority
      of the cases are because of an IgE-mediated allergic mechanism. This fact
      contrasts with studies in adults, where this percentage is much greater.

PMID- 14675478
TI  - Hyper-IgM syndrome with CHARGE association.
AB  - A girl with coloboma of the iris, sensorineural deafness, growth delay,
      distinctive face, and cranial nerve dysfunction was diagnosed of CHARGE
      association in the first year of life. She presented with repeated otitis. At 3
      yr of age, the patient suffered a septicemia (Streptococcus pneumoniae,
      Corynebacterium sp.). The immunoglobulin G (IgG) and IgA serum levels were
      decreased, IgM increased and cellular immunity parameters were normal, supporting
      the diagnosis of hyper-IgM (HIM) syndrome. The sequence of CD40 ligand and
      cytidine deaminase genes were normal. From then on, she was receiving
      immunoglobulin intravenously with an excellent outcome. Here, we report the first
      case of CHARGE association and HIM syndrome in the same patient. Although the
      cause could not be identified, a non-random link is likely.

PMID- 14675481
TI  - Ex vivo screening for immunodominant viral epitopes by quantitative real time
      polymerase chain reaction (qRT-PCR).
AB  - The identification and characterization of viral epitopes across the Human
      Leukocyte Antigen (HLA) polymorphism is critical for the development of actives
      specific or adoptive immunotherapy of virally-mediated diseases. This work
      investigates whether cytokine mRNA transcripts could be used to identify epitope
      specific HLA-restricted memory T lymphocytes reactivity directly in fresh
      peripheral blood mononuclear cells (PBMCs) from viral-seropositive individuals in
      response to ex vivo antigen recall. PBMCs from HLA-A*0201 healthy donors,
      seropositive for Cytomegalovirus (CMV) and Influenza (Flu), were exposed for
      different periods and at different cell concentrations to the HLA-A*0201
      restricted viral FluM158-66 and CMVpp65495-503 peptides. Quantitative real time
      PCR (qRT-PCR) was employed to evaluate memory T lymphocyte immune reactivation by
      measuring the production of mRNA encoding four cytokines: Interferon-gamma (IFN
      gamma), Interleukin-2 (IL-2), Interleukin-4 (IL-4), and Interleukin-10 (IL-10).
      We could characterize cytokine expression kinetics that illustrated how cytokine
      mRNA levels could be used as ex vivo indicators of T cell reactivity.
      Particularly, IFN-gamma mRNA transcripts could be consistently detected within 3
      to 12 hours of short-term stimulation in levels sufficient to screen for HLA
      restricted viral immune responses in seropositive subjects. This strategy will
      enhance the efficiency of the identification of viral epitopes independently of
      the individual HLA phenotype and could be used to follow the intensity of immune
      responses during disease progression or in response to in vivo antigen-specific
      immunization.

PMID- 14675480
TI  - Knockout of ERK5 causes multiple defects in placental and embryonic development.
AB  - BACKGROUND: ERK5 is a member of the mitogen activated protein kinase family
      activated by certain mitogenic or stressful stimuli in cells, but whose
      physiological role is largely unclear. RESULTS: To help determine the function of
      ERK5 we have used gene targeting to inactivate this gene in mice. Here we report
      that ERK5 knockout mice die at approximately E10.5. In situ hybridisation for
      ERK5, and its upstream activator MKK5, showed strong expression in the head and
      trunk of the embryo at this stage of development. Between E9.5 and E10.5,
      multiple developmental problems are seen in the ERK5-/- embryos, including an
      increase in apoptosis in the cephalic mesenchyme tissue, abnormalities in the
      hind gut, as well as problems in vascular remodelling, cardiac development and
      placental defects. CONCLUSION: Erk5 is essential for early embryonic development,
      and is required for normal development of the vascular system and cell survival.

PMID- 14675482
TI  - Autoregression as a means of assessing the strength of seasonality in a time
      series.
AB  - BACKGROUND: The study of the seasonal variation of disease is receiving
      increasing attention from health researchers. Available statistical tests for
      seasonality typically indicate the presence or absence of statistically
      significant seasonality but do not provide a meaningful measure of its strength.
      METHODS: We propose the coefficient of determination of the autoregressive
      regression model fitted to the data () as a measure for quantifying the strength
      of the seasonality. The performance of the proposed statistic is assessed through
      a simulation study and using two data sets known to demonstrate statistically
      significant seasonality: atrial fibrillation and asthma hospitalizations in
      Ontario, Canada. RESULTS: The simulation results showed the power of the in
      adequately quantifying the strength of the seasonality of the simulated
      observations for all models. In the atrial fibrillation and asthma datasets,
      while the statistical tests such as Bartlett's Kolmogorov-Smirnov (BKS) and
      Fisher's Kappa support statistical evidence of seasonality for both, the
      quantifies the strength of that seasonality. Corroborating the visual evidence
      that asthma is more conspicuously seasonal than atrial fibrillation, the
      calculated for atrial fibrillation indicates a weak to moderate seasonality ( =
      0.44, 0.28 and 0.45 for both genders, males and females respectively), whereas
      for asthma, it indicates a strong seasonality ( = 0.82, 0.78 and 0.82 for both
      genders, male and female respectively). CONCLUSIONS: For the purposes of health
      services research, evidence of the statistical presence of seasonality is
      insufficient to determine the etiologic, clinical and policy relevance of
      findings. Measurement of the strength of the seasonal effect, as can be
      determined using the technique, is also important in order to provide a robust
      sense of seasonality.

PMID- 14675483
TI  - The extracellular matrix of porcine mature oocytes: origin, composition and
      presumptive roles.
AB  - The extracellular matrix (ECM) of porcine mature oocytes was revealed by
      transmission electron microscopy (TEM) after treatment with tannic acid and
      ruthenium red. Present in the perivitelline space (PVS) and on the surface of the
      zona pellucida (ZP), it appeared to be composed of thin filaments and granules at
      the interconnections of the filaments, which were interpreted respectively as
      hyaluronic acid chains and bound proteoglycans. In order to determine whether
      this material is produced by the corona cells (the same ECM was found also on the
      surface of the zona pellucida and between cumulus cells) or by the oocyte itself,
      the synthesis of glycoproteins and glycosaminoglycans was checked by
      autoradiography on semi-thin and thin sections observed by light and electron
      microscopy. Immature oocytes within or without cumulus cells, were incubated with
      L [3H-] fucose or L [3H-] glucosamine--precursors respectively of glycoproteins
      and hyaluronic acid or hyaluronan (HA) bound to proteoglycans--for various times
      (with or without chase) and at different stages during in vitro maturation. In
      the first case, incorporation was found in both cumulus cells and ooplasm
      (notably in the Golgi area for 3H-fucose) and labeled material accumulated in the
      ECM of the PVS and of the ZP surface. Labeling in the PVS with both precursors
      was maximum between metaphase I (MI) and metaphase II (MII) and was partially
      extracted by hyaluronidase but not by neuraminidase. Tunicamycin, an inhibitor of
      glycoprotein synthesis, significantly decreased the amount of 3H-fucose labeled
      molecules in the PVS and increased the incidence of polyspermic penetration
      during subsequent in vivo fertilization. Since cumulus-free oocytes also secreted
      3H-glucosamine containing compounds, both oocyte and cumulus cells probably
      contribute to the production of the ECM found in the PVS of mature oocytes. ECM
      and particularly its HA moiety present on both sides of the ZP may constitute a
      favourable factor for sperm penetration.

PMID- 14675484
TI  - Health-related quality of life deficits associated with varying degrees of
      disease severity in type 2 diabetes.
AB  - BACKGROUND: Diabetes is a chronic medical condition accompanied by a considerable
      health-related quality of life (HRQL) burden. The purpose of this analysis was to
      use generic measures of HRQL to describe HRQL deficits associated with varying
      degrees of severity of type 2 diabetes. METHODS: The RAND-12 physical and mental
      health composites (PHC and MHC, respectively) and Health Utilities Index Mark 3
      (HUI3) were self-completed by 372 subjects enrolled in a prospective, controlled
      study of an intervention to improve care for individuals with type 2 diabetes in
      rural communities. Analysis of covariance was used to assess differences in HRQL
      according to disease severity and control of blood glucose. Disease severity was
      defined in terms of treatment intensity, emergency room visits and absenteeism
      from work specifically attributable to diabetes. To control for potential
      confounding, the analysis was adjusted for important sociodemographic and
      clinical characteristics. RESULTS: The PHC and MHC were significantly lower for
      individuals treated with insulin as compared to diet alone (PHC: 41.01 vs 45.11,
      MHC: 43.23 vs 47.00, p < 0.05). Individuals treated with insulin had lower scores
      on the vision, emotion and pain attributes of the HUI3 than individuals managed
      with oral medication or diet. The PHC, MHC, pain attribute and overall score on
      the HUI3 captured substantial decrements in HRQL associated with absenteeism from
      work due to diabetes, while the burden associated with emergency room utilization
      for diabetes was seen in the PHC and HUI3 pain attribute. CONCLUSIONS: We
      concluded that generic measures of HRQL captured deficits associated with more
      severe disease in type 2 diabetes.

PMID- 14675485
TI  - The Aging Males' Symptoms (AMS) scale: review of its methodological
      characteristics.
AB  - BACKGROUND: The current paper reviews data from different sources to get a closer
      impression on the psychometric and other methodological characteristics of the
      Aging Males' Symptoms (AMS) scale gathered recently. The scale was designed and
      standardized as self-administered scale to (a) to assess symptoms of aging
      (independent from those which are disease-related) between groups of males under
      different conditions, (b) to evaluate the severity of symptoms over time, and (c)
      to measure changes pre- and post androgen replacement therapy. The scale is in
      widespread use (14 languages). METHOD: Original data from different studies in
      many countries were centrally analysed to evaluate reliability and validity of
      the AMS. RESULTS: Reliability measures (consistency and test-retest stability)
      were found to be good across countries, although the sample size was sometimes
      small. VALIDITY: The internal structure of the AMS in healthy and androgen
      deficient males, and across countries was sufficiently similar to conclude that
      the scale really measures the same phenomenon. The sub-scores and total score
      correlations were high (0.8-0.9) but lower among the sub-scales (0.5-0.7). This
      however suggests that the subscales are not fully independent. The comparison
      with other scales for aging males or screening instruments for androgen
      deficiency showed sufficiently good correlations, illustrating a good criterion
      oriented validity. The same is true for the comparison with the generic quality
      of-life scale SF36 where also high correlation coefficients have been shown.
      Methodological analyses of a treatment study of symptomatic males with
      testosterone demonstrated the ability of the AMS scale to measure treatment
      effect, irrespective of the severity of complaints before therapy. It was also
      shown that the AMS result can predict the independently generated (physician's)
      opinion about the individual treatment effect. CONCLUSION: The currently
      available methodological evidence points towards a high quality of the AMS scale
      to measure and to compare HRQoL of aging males over time or before/after
      treatment, it suggests a high reliability and high validity as far as the process
      of construct validation could be pressed ahead yet. But certainly more data will
      become available, particularly from ongoing clinical studies.

PMID- 14675486
TI  - Deep vein thrombosis: validation of a patient-reported leg symptom index.
AB  - INTRODUCTION: Deep vein thrombosis (DVT) is a serious health problem that affects
      more than 2 million people annually in the United States. Many of these patients
      develop asymptomatic DVT, but months to years later may experience symptomatic
      post-thrombotic syndrome (PTS). It is not known how many cases of PTS can be
      traced to "asymptomatic" DVT because venography is no longer routinely done and
      ultrasonography (US) may miss some asymptomatic clots. As a result, a clinical
      tool in addition to US to detect symptom emergence or exacerbation in patients
      after DVT would be of value. METHODS: Seventy-seven patients hospitalized with an
      acute DVT interviewed by telephone at 3-7 days, 30-40 days, and 12-months
      following discharge were included in this report. All were treated with a
      standard anticoagulation "Clinical Pathway Protocol" between April 1999 and
      January 2000. Using a 14-item Deep Vein Thrombosis Leg Symptom Index (DVT-LSI),
      patients were queried regarding leg pain, swelling, skin discoloration, cosmetic
      appearance, activity tolerance, emotional distress, and leg-related sleep
      problems. RESULTS: The DVT-LSI for each leg was reliable at all assessments, with
      instrument reliability (alpha coefficients) greater than 0.70 at all time points
      (range 0.71-0.87). DVT-LSI scores, and the percentage of patients exhibiting
      symptoms, were higher in the DVT-affected leg at all time points. Among patients
      with unilateral disease, symptom severity ratings were significantly worse for
      patients in the affected leg compared to the normal leg at all time points, with
      the exception of those with a right-leg DVT at 12 months. Patients with bilateral
      thrombi did not have different scores on one leg compared to the other.
      CONCLUSION: The DVT-LSI is useful in assessing symptomatic clinical outcomes in
      patients after diagnosis of DVT, and may represent a surrogate marker for DVT
      otherwise presumed to be asymptomatic.

PMID- 14675487
TI  - The proteome of human brain microdialysate.
AB  - BACKGROUND: Cerebral microdialysis has been established as a monitoring tool in
      neurocritically ill patients suffering from severe stroke. The technique allows
      to sample small molecules in the brain tissue for subsequent biochemical
      analysis. In this study, we investigated the proteomic profile of human cerebral
      microdialysate and if the identified proteins might be useful predictors for
      disease characteristics in stroke for tissue at risk in the contralateral
      hemisphere. We analysed cerebral protein expression in microdialysate from three
      stroke patients sampled from the hemisphere contralateral to the lesion. Using a
      proteomic approach based on two-dimensional gel electrophoresis and subsequent
      mass spectrometry, we created a protein map for the global protein expression
      pattern of human microdialyste. RESULTS: We found an average of 158 +/- 24 (N =
      18) protein spots in the human cerebral microdialysate and could identify 95
      spots, representing 27 individual proteins. Most of these have been detected in
      human cerebrospinal fluid before, but 10 additional proteins mainly of cerebral
      intracellular origin were identified exclusively in the microdialysate.
      CONCLUSIONS: The 10 proteins found exclusively in human cerebral microdialysate,
      but not in cerebrospinal fluid, indicate the possibility to monitor the
      progression of the disease towards deterioration. The correlation of protein
      composition in the human cerebral microdialysate with the patients' clinical
      condition and results of cerebral imaging may be a useful approach to future
      applications for neurological stroke diagnosis, prognosis, and treatment.

PMID- 14675488
TI  - Emerging Applications of Bacterial Spores in Nanobiotechnology.
AB  - Bacterial spores are robust and dormant life forms with formidable resistance
      properties, in part, attributable to the multiple layers of protein that encase
      the spore in a protective and flexible shield. The coat has a number of features
      pertinent to the emerging field of nanobiotechnology including self-assembling
      protomers and the capacity for engineering and delivery of foreign molecules.
      This review gives an account of recent progress describing the use of the spore,
      and specifically, the spore coat as a vehicle for heterologous antigen
      presentation and protective immunization (vaccination). As interest in the spore
      coat increases it seems likely that they will be exploited further for drug and
      enzyme delivery as well as a source of novel self-assembling proteins.

PMID- 14675489
TI  - Regulation of COX-2 transcription in a colon cancer cell line by Pontin52/TIP49a.
AB  - Cyclooxygenase-2 (COX-2) is expressed early in colon carcinogenesis and is known
      to play a crucial role in the progress of the disease. Here we show that the
      regulation of the expression of this enzyme in a colon cancer cell line, and in
      patients, is associated with overexpression of the Wnt pathway-associated
      proteins, Pontin52/TIP49a and LEF-1. Recently shown to be essential for
      transformation via the c-Myc pathway, Pontin52/TIP49a promotes COX-2 expression
      in tissue culture and is overexpressed in colon cancer tissue, co-localizing with
      COX-2 expression in transformed tissue, relative to paired normal tissue.

PMID- 14675490
TI  - Behaviour of filariae: morphological and anatomical signatures of their life
      style within the arthropod and vertebrate hosts.
AB  - This paper attempts to pinpoint the most original morphological anatomical
      features of the biology of filariae per se and those which are or could be
      important for triggering regulatory processes in the arthropod vector and
      uncontrolled pathogenic processes in the vertebrate hosts. The following stages
      are considered: the motile egg or newly-hatched larva, the microfilaria, in the
      lymphatic or blood vessels of its vertebrate host; the larva, its migrations and
      its intrasyncitial development in the hematophagous arthropod subverted as
      vector; its transfer to the vertebrate host, migratory properties through the
      lymphatic system, maturation, mating and, finally, egg laying in the tissues they
      reach. This synthesis is based on parasite morphological features and their
      functional interpretation, histological features in the different niches the
      filariae reach, and on quantitative analyses of filarial development at its
      different phases, as well as on the rare and valuable observations of living
      parasites in situ. Data have been drawn from various species of Onchocercidae
      from amphibians, reptiles, birds and mammals. These comparative analyses have
      revealed the major constraints to which the filariae, including those
      parasitizing humans, have been subjected during their evolution from their
      ancestors, the oviparous and heteroxenic spirurids. Emphasis is placed on
      mechanical events: resistance of the microfilariae to the currents in the blood
      or lymph vessels, regulatory processes induced in the vector mesenteron by the
      movements of the ingested microfilariae, transient disruption by the
      microfilarial cephalic hook of the vectors' tissues and cell membranes during
      microfilarial translocation, attachment of males to females during mating by
      means of 'non-slip' systems, etc. Like other nematodes, filariae are equipped
      with sensory organs and a locomotor system, composed of the muscles and of the
      original osmoregulatory-excretory cell. Any change in one of these elements will
      result in the destruction of the filaria, at some stage of its development. In
      the vertebrate host, the intravascular stages will no longer be able to resist
      being carried passively towards the organs of destruction such as the lymph nodes
      or the lungs.

PMID- 14675491
TI  - Molecular monitoring of the Leu-164 mutation of dihydrofolate reductase in a
      highly sulfadoxine/pyrimethamine-resistant area in Africa.
AB  - The selection of point mutation at codon 164 (from isoleucine to leucine) of the
      dihydrofolate reductase (DHFR) enzyme in Plasmodium falciparum is associated with
      high sulfadoxine /pyrimethamine (SP) resistance. Using the yeast expression
      system that allows the detection of dhfr allele present at low level, the
      presence of this mutation had previously been reported between 1998-1999 in
      Muheza, Tanzania, an area of high SP resistance. Eighty five P. falciparum
      isolates, obtained from the same area between 2002 and 2003, were analysed for
      the presence of Leu-164 mutation, using standard protocol based on PCR-RFLP. None
      of the isolates had the Leu-164 mutation.

PMID- 14675493
TI  - Factors affecting the intention of providers to deliver more effective continuing
      medical education to general practitioners: a pilot study.
AB  - BACKGROUND: Despite the importance of continuing medical education (CME) for GPs,
      there has been little research into how providers decide what types of CME to
      deliver to GPs. This study aimed to identify factors affecting the intention of
      providers to provide more effective types of CME; and to design a survey
      instrument which can be used to test the applicability of Triandis' model of
      social behaviour to the provision of CME to general practitioners. METHODS: This
      was a cross-sectional study on a convenience sample of 11 Australian providers of
      CME for interviews and a random sample of 25 providers for the pilot test. Open
      ended interviews structured on Triandis' theory were performed with key
      informants who provide CME to GPs. These were used to develop a pilot survey
      instrument to measure the factors affecting intention, resulting in a revised
      instrument for use in further research. RESULTS: There was a broad range of
      factors affecting providers' intention to deliver more effective forms of CME
      identified, and these were classifiable in a manner which was consistent with
      Triandis' model. Key factors affecting providers' intention were the attitude
      toward CME within organisations and the time and extra work involved.
      CONCLUSIONS: We identified a range of potential factors influencing the intention
      of providers to provide more effective forms of CME, in all categories of
      Triandis model. Those interested in increasing the choice of more effective CME
      activities available to GPs may need to broaden the methods used in working with
      providers to influence them to use more effective CME techniques. The interview
      material and questionnaire analysis of the pilot survey support the use of
      Triandis model. Further research is needed to validate Triandis'model for the
      intention to deliver more effective forms of CME. Such research will inform
      future strategies aimed at increasing the amount and choice of effective CME
      activities available for GPs.

PMID- 14675492
TI  - Unipolar late-onset depression: A comprehensive review.
AB  - BACKGROUND: The older population increases all over the world and so also does
      the number of older psychiatric patients, which manifest certain specific and
      unique characteristics. The aim of this article is to provide a comprehensive
      review of the international literature on unipolar depression with onset at old
      age. METHODS: The authors reviewed several pages and books relevent to the
      subject but did not search the entire literature because of it's overwhelming
      size. They chose to review those considered most significant. RESULTS: The
      prevalence of major depression is estimated to be 2% in the general population
      over 65 years of age. The clinical picture of geriatric depression differs in
      many aspects from depression in younger patients. It is not yet clear whether it
      also varies across cultures and different socio-economic backgrounds. Biological
      data suggest that it is associated with an increased severity of subcortical
      vascular disease and greater impairment of cognitive performance. Many authors
      consider the existence of a somatic disorder to be related to the presence of
      depression in late life, even constituting a negative prognostic factor for the
      outcome of depression. Most studies support the opinion that geriatric depression
      carries a poorer prognosis than depression in younger patients. The therapeutic
      intervention includes pharmacotherapy, mainly with antidepressants, which is of
      established value and psychotherapy which is not equally validated. CONCLUSION: A
      significant number of questions regarding the assessment and treatment of
      geriatric depression remain unanswered, empirical data are limited, and further
      research is necessary.

PMID- 14675494
TI  - Rational choice of cholinesterase inhibitor for the treatment of Alzheimer's
      disease in Canada: a comparative economic analysis.
AB  - BACKGROUND: Cholinesterase inhibitors, such as galantamine, donepezil and
      rivastigmine are approved for symptomatic treatment of Alzheimer's Disease (AD)
      in Canada. In making choices amongst these drugs, one should consider their
      clinical merits and their economic implications. METHODS: Each drug's short-term
      efficacy was estimated based on independent Cochrane reviews of the clinical
      trials. Long-term clinical and economic outcomes were estimated using the
      Assessment of Health Economics in Alzheimer's Disease (AHEAD) model. RESULTS:
      While all treatments reduced the need for full-time care, only galantamine and
      donepezil 10 mg reduced the overall management costs of AD patients. The somewhat
      greater cognitive effect provided over six months by galantamine leads to the
      longest estimated delay before full-time care is required and, consequently to
      lower overall costs, with savings estimated at between 323 dollars and 4,246
      dollars. CONCLUSION: Although there is uncertainty in estimated results, the best
      information currently available suggests that the first choice for treatment of
      AD should be galantamine. These results should be interpreted with caution,
      however, as results are not based on direct comparisons among the drugs and the
      differences emerging from meta-analyses of the trials are relatively small.

PMID- 14675495
TI  - Genomic characterization of a repetitive motif strongly associated with
      developmental genes in Drosophila.
AB  - BACKGROUND: Non-coding DNA represents a high proportion of all metazoan genomes.
      Although an undetermined fraction of this DNA may be considered devoid of any
      function, it also contains important information residing in specific cis
      regulatory sequences. RESULTS: We report a 27 bp motif that is overrepresented
      within the fly genome. This motif does not show any significant similarity with
      transposon sequences and is strongly associated with genes involved in
      development and/or signal transduction. The 27 bp motif is preferentially located
      within introns, and has a tendency to be present in multiple copies around genes.
      Furthermore, it is often found embedded in known non-coding regulatory regions.
      The regulatory network defined by this motif is partially shared in D.
      pseudoobscura. CONCLUSION: We have identified a 27 bp cis-regulatory sequence
      widely distributed within the Drosophila genome in association with developmental
      genes. This motif may be very useful towards the annotation of functional
      regulatory regions within the Drosophila genome and the construction of
      regulatory networks of Drosophila development.

PMID- 14675498
TI  - Diet quality among older Quebecers as assessed by simple indicators.
AB  - To determine whether older Quebecers are eating adequately and whether summary
      scores represent diet quality, a representative subset of participants aged 55 to
      74 (weighted n=460, 47% male) was studied from the 1990 Enquete quebecoise sur la
      nutrition dataset. Participants' diet quality was scored from adjusted 24-hour
      recalls. Foods were coded into Canada's Food Guide to Healthy Eating food groups.
      Usual Dietary Adequacy Score (maximum=18) and Dietary Diversity Score (maximum=4)
      were calculated from adjusted food guide portions and validated internally in
      relation to achievement of nutrient recommendations using correlation analysis.
      Average usual Dietary Adequacy Score (mean +/- standard error) was 14.96 +/- 0.15
      (men) and 13.72 +/- 0.15 (women). Only 7% of men and 1% of women achieved the
      maximum usual score. Forty-four percent of men and 45% of women scored a usual
      Dietary Diversity Score of 3, and 55% of men and 50% of women achieved 4. Thus,
      approximately half of older Quebecers showed inadequate dietary variety, and
      consumed fewer than the minimum recommended number of servings from certain food
      groups. Summary diet quality indicators are useful for tracking diet quality, and
      provide critical data for planning nutrition education programs targeting older
      persons.

PMID- 14675496
TI  - Metabolic reconstruction of sulfur assimilation in the extremophile
      Acidithiobacillus ferrooxidans based on genome analysis.
AB  - BACKGROUND: Acidithiobacillus ferrooxidans is a gamma-proteobacterium that lives
      at pH2 and obtains energy by the oxidation of sulfur and iron. It is used in the
      biomining industry for the recovery of metals and is one of the causative agents
      of acid mine drainage. Effective tools for the study of its genetics and
      physiology are not in widespread use and, despite considerable effort, an
      understanding of its unusual physiology remains at a rudimentary level. Nearly
      complete genome sequences of A. ferrooxidans are available from two public
      sources and we have exploited this information to reconstruct aspects of its
      sulfur metabolism. RESULTS: Two candidate mechanisms for sulfate uptake from the
      environment were detected but both belong to large paralogous families of
      membrane transporters and their identification remains tentative. Prospective
      genes, pathways and regulatory mechanisms were identified that are likely to be
      involved in the assimilation of sulfate into cysteine and in the formation of Fe
      S centers. Genes and regulatory networks were also uncovered that may link sulfur
      assimilation with nitrogen fixation, hydrogen utilization and sulfur reduction.
      Potential pathways were identified for sulfation of extracellular metabolites
      that may possibly be involved in cellular attachment to pyrite, sulfur and other
      solid substrates. CONCLUSIONS: A bioinformatic analysis of the genome sequence of
      A. ferrooxidans has revealed candidate genes, metabolic process and control
      mechanisms potentially involved in aspects of sulfur metabolism. Metabolic
      modeling provides an important preliminary step in understanding the unusual
      physiology of this extremophile especially given the severe difficulties involved
      in its genetic manipulation and biochemical analysis.

PMID- 14675499
TI  - Diet, obesity and education in three age groups of Saskatchewan women.
AB  - Research on relationships between socioeconomic status and Canadians' diet is
      limited. The current study investigated differences by education in dietary
      variables shown to be related to obesity; it included three age groups of
      Saskatchewan women who participated in the 1992 to 1993 Heart Health Intervention
      Evaluation baseline study. Multistage sampling was used to select randomly from
      the Saskatchewan Health Insurance Registration File. The overall response rate
      was 42.6%; a sample representative of the general Saskatchewan population was
      obtained. Three-day estimated food records and demographic information from 396
      women aged 18 to 74 years were subdivided into three age categories: 18 to 34
      years, 35 to 54 years, and 55 to 74 years. For the 18- to 34-year group, obesity
      was significantly more prevalent with lower education; trends were similar for
      the older age groups. Under-reporting of energy intake (indicated by an energy
      intake:basal metabolic rate ratio of <1.1) was related to obesity but not to
      education. The greatest differences in diet between educational groups were
      observed in the 18- to 34-year group; fewer differences existed in the 35- to 54
      year group, and none in the 55- to 74-year group. Health promotion efforts need
      to be targeted appropriately, and based on differences in dietary intakes by
      socioeconomic group. Research should help promote an understanding of the reasons
      for differences in diet by socioeconomic status.

PMID- 14675500
TI  - Nutritional risk in vulnerable community-living seniors.
AB  - The purpose of this study was to quantify nutritional risk in a convenience
      sample of vulnerable, community-living seniors, and to determine patterns of
      nutritional risk in these seniors. The sample consisted of 367 seniors who
      provided health, functional, and nutritional risk information during an interview
      in which the Seniors in the Community: Risk Evaluation for Eating and Nutrition
      questionnaire was used. The majority (73.6%) of the sample was female, and the
      mean age was 79 years. Nutritional risk was identified in 68.7% of the sample,
      with 44.4% being at high nutritional risk. Common nutritional risk factors were
      weight change, restricting food, low fruit and vegetable intake, difficulty with
      chewing, cooking, or shopping, and poor appetite. Principal components analysis
      identified four independent components within the Seniors in the Community: Risk
      Evaluation for Eating and Nutrition questionnaire; these components can be
      described as low food intake, poor appetite, physical and external challenges,
      and instrumental activity challenges. Data are sparse on nutritional risk in
      community-living Canadian seniors; despite methodologic limitations in the
      recruitment process, this study provides some indication of the level of
      nutrition problems. The patterns of nutritional risk identified in this
      vulnerable population may help providers identify useful strategies for
      ameliorating risk. The Seniors in the Community: Risk Evaluation for Eating and
      Nutrition questionnaire could be used to identify risk and patterns of risk in
      Canadian seniors, so that treatment could be individualized.

PMID- 14675501
TI  - Eat Smart! Ontario's Healthy Restaurant Program: a survey of participating
      restaurant operators.
AB  - Eat Smart! Ontario's Healthy Restaurant Program is a standard provincial health
      promotion program. Public health units grant an award of excellence to
      restaurants that meet designated standards in nutrition, food safety, and non
      smoking seating. The purpose of this study was to assess whether program
      objectives for participating restaurant operators were achieved during the first
      year of program implementation, and to obtain operators' recommendations for
      improving the program. Dillman's tailored design method was used to design a mail
      survey and implement it among participating operators (n = 434). The design
      method, which consisted of four mail-outs, yielded a 74% response rate. Fifty
      percent of respondents operated family-style or quick-service restaurants, and
      82% of respondents learned about the program from public health inspectors.
      Almost all respondents (98%) participated in the program mainly to have their
      establishments known as clean and healthy restaurants, 65% received and used
      either point-of-purchase table stands or postcards to promote the program, and
      98% planned to continue participating. The respondents' suggestions for improving
      the program were related to the award ceremony and program materials, media
      promotion, communication, education, and program standards. Program staff can use
      the findings to enhance the program.

PMID- 14675502
TI  - Issues in implementing school nutrition policies.
AB  - The implementation of school nutrition policies poses a challenge to dietitians
      as they work with schools to increase the availability of nutritious foods. An
      analysis of the implementation of the Food and Nutrition Policy for New Brunswick
      Schools, proclaimed by the department of education in 1991, revealed four factors
      that influenced implementation: selling food for profit, student choice,
      interpretation of the policy, and the approach to implementation. From 1997 to
      1999, data were obtained from 50 participants at the provincial, district, and
      school levels through semi-structured interviews; supporting evidence was
      obtained through a review of pertinent documents. The policy goal was to develop
      good eating habits among schoolchildren. The policy objective to have all food
      services follow national guidelines for healthy eating was so controversial that
      implementation was inconsistent and had little impact on school foods. Opponents
      objected when the sale of certain foods was curtailed, felt the policy limited
      student choice, were unsure how to interpret it, and resented the department's
      top-down approach. Dietitians, who had minimal involvement with the New Brunswick
      policy, need to consider carefully how to work with educational agencies to
      combine support and pressure to foster the capacity and willingness of schools to
      implement nutrition policies.

PMID- 14675503
TI  - Assessment of the Mission Nutrition nutrition education program.
AB  - In 1998, Dietitians of Canada and the team of registered dietitians at Kellogg
      Canada Inc. partnered to develop Mission Nutrition, a national bilingual
      nutrition education program that provides curriculum-based resources to teachers.
      The main objectives of this study were to measure the awareness and utility of
      the Mission Nutrition program among elementary teachers, and to identify
      opportunities to enhance the Mission Nutrition resources to increase use. A ten
      minute telephone survey was conducted with a representative sample of 203
      elementary school teachers. A sub-sample of 20 teachers then participated in a
      more in-depth 30-minute telephone survey. A need for increased promotion of the
      Mission Nutrition program was identified on the basis of the 22% awareness among
      teachers participating in the initial interview. All teachers who had used the
      educator guides and student activity sheets reported that they would use them
      again. Teachers found that the Mission Nutrition materials were well-researched
      and contained useful activities relevant to students. The findings indicate that,
      to be most effective, nutrition education resources should be provided in a ready
      to-use format and integrated with core curricula. Teachers also suggested that
      materials should include fresh ideas to engage students at different grade
      levels, and ways to involve parents. Dietitians are ideally positioned to work
      collaboratively with educators to develop these types of nutrition education
      resources.

PMID- 14675504
TI  - An arresting experiment: domestic violence victim experiences and perceptions.
AB  - This study looks at the experiences and perceptions that domestic violence
      victims reported with Mills's power model. The victims' partners were the primary
      research participants in an arrest experiment. The following were empirically
      examined: the occurrence of violence following suspect arrest, victim perceptions
      of personal and legal power, victim satisfaction with the police, and victim
      perceptions of safety following legal intervention. Race and two victim resource
      measures (i.e., employment status and income advantage) explained variance in
      perceptions of independence. A police empowerment scale was used to measure legal
      power. It was found that arrest affected the probability of re-occurring domestic
      violence. Suspect arrest and the victim's perceptions of legal power were related
      to perceptions of safety following police intervention. The study concludes with
      some implications for domestic violence research, programs, and perspectives.

PMID- 14675505
TI  - Counseling services for battered women: a comparison of outcomes for physical and
      sexual assault survivors.
AB  - Approximately 15% of married or cohabiting women and as many as 60% of battered
      women are raped at least once by their partners. This study compared community
      based counseling outcomes of battered women with outcomes of women who were both
      raped and battered by their partners. Over time, both groups improved in
      wellbeing and coping. Although those both battered and raped progressed more in
      counseling, they had lower scores before and after counseling compared to women
      who were battered only. Implications for research and intervention are discussed.

PMID- 14675506
TI  - Does alcohol make a difference? Within-participants comparison of incidents of
      partner violence.
AB  - Episodes of husband-to-wife violence in which the husband consumed alcohol were
      compared with episodes of husband-to-wife violence, reported by the same
      individuals, in which the husband was not drinking. Among this community sample
      of newlyweds, wife reports, but not husband reports, indicated that violent
      episodes in which the husband was drinking included more acts of violence and
      were more likely to involve severe violence. Both wife and husband reports
      indicated that wives were more likely to be physically aggressive in husband
      drinking episodes compared to sober episodes. However, whereas wives reported
      that their aggressive behavior was a response to husband aggression, husbands
      reported that wives were more likely to initiate violence in these episodes.
      Violent episodes that include alcohol may be more severe and more mutually
      violent than sober episodes. Discrepancies between husband and wife reports may
      reflect differences in recall or self-serving biases.

PMID- 14675507
TI  - Evaluation of a national prison-based treatment program for sexual offenders in
      England and Wales.
AB  - Treatment efficacy is described for a sample of sexual offenders who had
      undertaken treatment in United Kingdom prisons (N = 647) and for a
      retrospectively selected comparison group (N = 1,910). The outcomes under
      observation in this study were sexual, sexual and/or violent, and general
      reconviction. Treatment impact was also examined in relation to offenders' risk
      of reconviction. The treatment group had slightly lower 2-year sexual
      reconviction rates than the comparison group, but these differences were not
      statistically significant. Significant differences were found between the
      treatment and comparison group for sexual and/or violent reconviction. Further
      analysis suggested that treatment produced a reduction in the probability of
      sexual and/or violent reconviction (p <.05) when other relevant variables were
      controlled for. General reconviction rates were consistently lower in the
      treatment group, but these differences were not significant.

PMID- 14675508
TI  - Victimization and perpetration among perinatal substance abusers.
AB  - This study examined associations between demographic, psychiatric, substance
      abuse, and childhood abuse variables and past 30-day victimization and
      perpetration among 77 perinatal substance abusers. Victimization rates were 70%
      emotional, 34% physical, 29% sexual, and 42% personal freedom violations. For
      perpetration, incidence was 71% emotional, 25% physical, 5% sexual, and 9%
      personal freedom violations. Through univariate regression, Addiction Severity
      Index (ASI) psychiatric and drug composite scores, childhood physical abuse,
      borderline personality disorder (BPD) and post-traumatic stress disorder (PTSD)
      were found to significantly predict victimization. In contrast, ASI psychiatric
      and drug composite scores, BPD, PTSD, and aggressive-sadistic and antisocial
      personality disorders were found to significantly predict perpetration. In
      multiple regression models, ASI drug and psychiatric composite scores accounted
      for the majority of the variance for both victimization and perpetration,
      suggesting that women with high ASI scores should be queried about their
      involvement in abusive acts at time of admission to drug treatment.

PMID- 14675509
TI  - The Self-Appraisal Questionnaire: a self-report measure for predicting recidivism
      versus clinician-administered measures: a 5-year follow-up study.
AB  - In this study, the effectiveness of the Self-Appraisal Questionnaire (SAQ), a
      self-report measure for predicting release outcome, is examined as compared to
      clinician-administered and widely used risk prediction measures, over a 5-year
      period. The SAQ was administered along with four similar, but clinician
      administered, measures to 91 federally sentenced Canadian male offenders prior to
      their release to the community. Follow-up data were collected for a 60-month
      period. Outcome criteria measures were violent and general recidivism. Results
      indicated that the SAQ is at least as effective as the four other measures in
      predicting postrelease outcome. The advantages of using the SAQ as a self-report
      measure as opposed to clinician-administered measures are discussed.

PMID- 14675510
TI  - Psychopathological profile of men convicted of gender violence: a study in the
      prisons of Spain.
AB  - In this article, a description of the demographic, penal, and psychopathological
      characteristics of 54 men who are in prison because of having committed a serious
      offense of gender violence was carried out. Furthermore, a comparison of all the
      variables studied between the participants with homicide and those without
      homicide was done. The results showed the existence of irrational beliefs both
      about women and violence as a strategy to cope with everyday difficulties, as
      well as a general inadaptation to daily life. However, from a psychopathological
      point of view, in spite of not observing a high degree of symptomatology in the
      sample, the psychiatric and penal antecedents and current emotional instability
      were much more frequent and severe in people who had not committed homicide.
      Therefore, two possible differential profiles among the violent men are
      presented.

PMID- 14675511
TI  - The relationship between the quantity of alcohol consumed and the severity of
      sexual assaults committed by college men.
AB  - Researchers have suggested that intoxicated perpetrators may act more violently
      than other perpetrators, although empirical findings have been mixed. Past
      research has focused on whether or not alcohol was consumed, rather than the
      quantity consumed, and this may explain these inconsistent findings. The authors
      hypothesized that the quantity of alcohol consumed would have a curvilinear
      relationship to the severity of the assault. Data were collected from 113 college
      men who reported that they had committed a sexual assault since the age of 14.
      The quantity of alcohol that perpetrators consumed during the assault was
      linearly related to how much aggression they used and was curvilinearly related
      to the type of sexual assault committed. The quantity of alcohol that victims
      consumed during the assault was linearly related to the type of sexual assault
      committed. Strategies for improving assessment of alcohol consumption in sexual
      assault research are discussed.

PMID- 14675512
TI  - Symptoms and clinical findings from the musculoskeletal system among operators at
      a call centre in Sweden--a 10-month follow-up study.
AB  - The musculoskeletal health among 57 operators at 1 call centre in Sweden was
      studied with 10 monthly follow-ups, parallel to a reference group of 1,226
      professional computer users in other occupations. Operators at this call centre
      were more symptom-loaded than the other professional computer users in spite of
      their younger age and shorter exposure to computer work. Symptoms were long
      lasting or recurrent. Muscle tenderness and nerve affections in the neck-shoulder
      region were the most common specific findings and diagnoses at medical
      examination of incident symptom cases. More extensive studies should be done on
      the working conditions and health status among call centre workers.

PMID- 14675513
TI  - Examining RULA's postural scoring system with selected physiological and
      psychophysiological measures.
AB  - The Rapid Upper Limb Assessment (RULA) survey is a posture-sampling tool used
      specifically to examine the level of risk associated with upper limb disorders of
      individual workers. This paper examines the relationship between RULA's postural
      scoring system and measures of surface electromyography (EMG), self-reports of
      discomfort, and job attitude questionnaires. Twenty participants each performed a
      30-min typing task on a computer in 3 working postures based on RULA's scoring
      system. A statistically significant difference was found only in perceived
      discomfort. The perceived discomfort results demonstrated that RULA was able to
      identify "high risk" postures. The next question we need to ask is, does
      perceived discomfort result in tissue damage, or does tissue damage yield
      discomfort?

PMID- 14675514
TI  - Prevention of deep vein thrombosis in VDU work.
AB  - This paper introduces preventive measures against Deep Vein Thrombosis (DVT)
      during Visual Display Units (VDU) work. Four experiments were conducted in order
      to address this issue. The effectiveness of the preventative measures was
      evaluated by measuring foot swelling. The results indicated that the following 3
      methods would be particularly effective: (a) occasionally adopting a reclining
      posture with a footrest, (b) 10-min walking every 50-60 min of VDU work, and (3)
      stretching. In addition we predicted that taking a deep breath could sometimes be
      effective. DVT is likely to occur in daily life and its incidence can be related
      to the long-term postures associated with VDU work. This paper suggests that VDU
      workers should be aware of the risk of DVT and take preventative measures.

PMID- 14675515
TI  - Comparison between the strain indicator HRV of a head-based virtual retinal
      display and LC-head mounted displays for augmented reality.
AB  - Augmented Reality uses Head Mounted Displays (HMD) to overlay the real word with
      additional virtual information. Virtual Retinal Displays (VRD), a new display
      technology, no longer requires Liquid Crystal Displays (LCD). VRD technology
      addresses the retina directly with a single laser stream of pixels. There are no
      studies on the user's informational strain in this new VRD technology. Various
      papers have shown that Heart Rate Variability (HRV) is a valid indicator for the
      user's informational strain. An empirical test revealed no difference in the
      user's HRV between VRD technology and LCD technology. Consequently, there seems
      to be a comparable user informational strain regarding the display types.

PMID- 14675516
TI  - Visual strain and lighting preferences of VDT users under different lighting
      systems.
AB  - Lighting influences users' visual strain and well-being. Therefore creating
      lighting that ensures visual work conditions do not result in visual fatigue is a
      preventive activity. The aim of the study was to model different lighting systems
      for visual display terminal (VDT) work and to determine their influence on users'
      visual strain and preferences. The results of the study showed that visual
      fatigue was lowest for indirect and compound lighting systems. On the other hand,
      in general, direct lighting realized by "dark-light" luminaires was the most
      preferred lighting system. Some interesting differences related to age, gender,
      and VDT work experience were found. On the basis of the obtained results lighting
      designers can be provided with some guidance.

PMID- 14675517
TI  - Effect of subjective and objective workload on asthenopia at VDU workplaces.
AB  - An ergophthalmological tool has been developed to investigate effects of
      subjective and objective workload on work-related visual complaints (asthenopia).
      In field studies on different visual display unit (VDU) workplaces effects of
      objective and subjective workload, work intensity, and work breaks (5-9 min/hour)
      could be found. It could be shown that during the first hours of VDU work,
      asthenopic complaints have the tendency to follow effective workload. With
      increasing working time the effect of a general and visual fatigue overlaps other
      reported visual complaints in the majority of cases.

PMID- 14675518
TI  - An attempt at preventing asthenopia among VDT workers.
AB  - We report the results of 3 surveys of visual display terminal (VDT) users who
      took a minibreak during which they viewed a stereoscopic image of a repeating
      parallel pattern showing planets. The single image stereogram method employed is
      called Stretch Eye (TM), and we evaluated the effects of Stretch Eye (TM) on
      asthenopia. An accommodative relaxation of about 1 D was observed in participants
      while they were gazing at the image. The employees of 2 information technology
      companies were evaluated according to a visual analogue scale (VAS) for
      subjective symptoms of asthenopia and eyesight. The results showed that Stretch
      Eye (TM) was effective in easing visual fatigue due to VDT work and it improved
      eyesight under working conditions.

PMID- 14675519
TI  - A new approach to the mouse arm syndrome.
AB  - OBJECTIVES: The study validates a new computer mouse concept. The tested device
      is a small mouse with a pivoting pen-shaped handle. The hypothesis behind the
      design is the assumptions that the pen grip requires less static tension than the
      normal mouse grip and that fine-motor, high precision tasks normally are done
      with finger movements with forearm at rest. METHODS: Four muscles were monitored
      with electromyography (EMG) during work with a new mouse and with a traditional
      mouse. RESULTS: EMG activity was significant lower, in M. pronator teres--46%, M.
      extensor digitorum--46%, M. trapezius--69%, and M. levator scapulae--82%, during
      work with the new mouse as compared to the traditional mouse. CONCLUSION:
      Altering the design of the computer mouse can significantly reduce muscular
      tension.

PMID- 14675520
TI  - The effects of the level of alertness during the rest period on subsequent
      performance.
AB  - The aim of this study was to examine how to take an effective rest to prevent a
      decline in alertness at work. The relationship between alertness during the rest
      period and subsequent task performance were investigated. The
      electroencephalogram (EEG) during the rest period was classified into 3 types,
      and these types had a significant effect on performance after the rest period.
      Type 1 (increasing in theta, alpha 2, and beta 1 power) was the best one for
      carrying out the task, whereas performance gradually declined in Type 3 (no
      change in EEG activity). In the case of Type 1, the method that would relieve
      sleep inertia had a more positive impact on performance after the rest period.

PMID- 14675521
TI  - Reducing musculoskeletal discomfort: effects of an office ergonomics workplace
      and training intervention.
AB  - Effects of an office ergonomics workplace and training intervention on workers'
      knowledge and self-reported musculoskeletal pain and discomfort were
      investigated. An instructional systems design process was used to develop an
      office ergonomics training program and the evaluation tools used to measure the
      effectiveness of the training program on workers' office ergonomics knowledge and
      skills. It was hypothesized that the training and workplace intervention would
      allow the worker to more effectively use their workplace through increased office
      ergonomics knowledge and skills. Following the intervention, there was a
      significant increase in workers' office ergonomics knowledge and awareness. Self
      reported work-related musculoskeletal disorders significantly decreased for the
      group who had a workplace change and received ergonomic training relative to a
      workplace change-only group and a no intervention control group.

PMID- 14675522
TI  - Sitting posture, postural discomfort, and visual performance: a critical view on
      the interdependence of cognitive and anthropometric factors in the VDU workplace.
AB  - The study focuses on individual and standard visual display unit (VDU) workplaces
      with respect to performance and muscular load. Three different work settings were
      realized: The workplace was either adjusted to individual preferences or to the
      European standard. The third condition mirrored exactly the individual setting,
      however participants were told that it was set according to another standard.
      Dependent variables were visual performance in a search task, the rated muscular
      load, and individual preferences. Results show that both individual work settings
      yielded a superior performance as compared to the standard. However, performance
      and muscular comfort improved when participants knew they had adjusted the
      workplace. Apparently, VDU users follow a intuitive rationale adjusting their
      work setting minimizing muscular load and optimizing performance.

PMID- 14675523
TI  - Visual Costs of the Inhomogeneity of Luminance and Contrast by Viewing LCD-TFT
      Screens Off-Axis.
AB  - In this study the anisotropic characteristics of TFT-LCD (Thin-Film-Transistor
      Liquid Crystal Display) screens were examined. Anisotropy occurs as the
      distribution of luminance and contrast changes over the screen surface due to
      different viewing angles. On the basis of detailed photometric measurements the
      detection performance in a visual reaction task was measured in different viewing
      conditions. Viewing angle (0 degrees, frontal view; 30 degrees, off-axis; 50
      degrees, off-axis) as well as ambient lighting (a dark or illuminated room) were
      varied. Reaction times and accuracy of detection performance were recorded.
      Results showed TFT's anisotropy to be a crucial factor deteriorating performance.
      With an increasing viewing angle performance decreased. It is concluded that
      TFT's anisotropy is a limiting factor for overall suitability and usefulness of
      this new display technology.

PMID- 14675524
TI  - Evidence-based ergonomics. A comparison of Japanese and American office layouts.
AB  - There is a variety of alternatives in office layouts. Yet the theoretical basis
      and criteria for predicting how well these layouts accommodate employees are
      poorly understood. The objective of this study was to evaluate criteria for
      selecting office layouts. Intensive computer workers worked in simulated office
      layouts in a controlled experimental laboratory. Eye movement measures indicate
      that knowledge work requires both concentration and interaction. Findings pointed
      to one layout as providing optimum balance between these 2 requirements.
      Recommendations for establishing a theoretical basis and design criteria for
      selecting office layouts based on work style are suggested.

PMID- 14675525
TI  - Affective computing--a rationale for measuring mood with mouse and keyboard.
AB  - Emotions are an increasingly important factor in Human-Computer Interaction
      (HCI). Up to the present, emotion recognition in HCI implies the use of explicit
      or intrusive methods, for example, video cameras or physiological measurements.
      We are developing and evaluating a method for the measurement of affective states
      through motor-behavioral parameters from standard input devices (mouse and
      keyboard).

PMID- 14675526
TI  - Symmetry, selectivity, and the 2003 Nobel Prize.

PMID- 14675527
TI  - SCF-mediated proteolysis and negative regulation in ethylene signaling.
AB  - Ethylene is an important hormonal regulator of plant growth that acts by
      regulating gene expression. In this issue of Cell, Guo and Ecker, and Potuschak
      et al., show that ethylene increases the abundance of the transcription factor
      EIN3, an activator of ethylene-inducible genes, by relieving its SCF-mediated
      destruction.

PMID- 14675528
TI  - Another cytoskeleton in the closet.
AB  - Many eukaryotic cells contain up to three families of cytoskeletal proteins that
      are responsible for the spatial organization of the cell. Although the
      prokaryotic origins of the actin and tubulin families have now been established,
      the origin of the third was unknown. In this issue of Cell, provide evidence that
      the third family, comprising the intermediate filaments, also has origins in
      bacteria and is responsible for producing curved cells.

PMID- 14675529
TI  - Coupled folding during translation initiation.
AB  - The structure of the eukaryotic initiation factor eIF4E bound to a cognate domain
      of eIF4G and m(7)GDP in this issue of Cell shows that these factors undergo
      coupled folding to form a stable complex with high cap binding activity that
      promotes efficient ribosomal attachment to mRNA during translation initiation.

PMID- 14675530
TI  - The secret life of ACE2 as a receptor for the SARS virus.
AB  - The membrane-associated carboxypeptidase angiotensin-converting enzyme 2 (ACE2)
      is an essential regulator of heart function. Now, Li at al. identify and
      characterize an unexpected second function of ACE2 as a partner of the SARS-CoV
      spike glycoprotein in mediating virus entry and cell fusion.

PMID- 14675531
TI  - A central role of the BK potassium channel in behavioral responses to ethanol in
      C. elegans.
AB  - The activities of many neuronal proteins are modulated by ethanol, but the
      fundamental mechanisms underlying behavioral effects of ethanol remain unclear.
      To identify mechanisms responsible for intoxication, we screened for
      Caenorhabditis elegans mutants with altered behavioral responses to ethanol. We
      found that slo-1 mutants, which were previously recognized as having slightly
      uncoordinated movement, are highly resistant to ethanol in two behavioral assays.
      Numerous loss-of-function slo-1 alleles emerged from our screens, indicating that
      slo-1 has a central role in ethanol responses. slo-1 encodes the BK potassium
      channel. Electrophysiological analysis shows that ethanol activates the channel
      in vivo, which would inhibit neuronal activity. Moreover, behaviors of slo-1 gain
      of-function mutants resemble those of ethanol-intoxicated animals. These results
      demonstrate that selective activation of BK channels is responsible for acute
      intoxicating effects of ethanol in C. elegans. BK channel activation may explain
      a variety of behavioral responses to ethanol in invertebrate and vertebrate
      systems.

PMID- 14675532
TI  - Plant responses to ethylene gas are mediated by SCF(EBF1/EBF2)-dependent
      proteolysis of EIN3 transcription factor.
AB  - Plants use ethylene gas as a signal to regulate myriad developmental processes
      and stress responses. The Arabidopsis EIN3 protein is a key transcription factor
      mediating ethylene-regulated gene expression and morphological responses. Here,
      we report that EIN3 protein levels rapidly increase in response to ethylene and
      this response requires several ethylene-signaling pathway components including
      the ethylene receptors (ETR1 and EIN4), CTR1, EIN2, EIN5, and EIN6. In the
      absence of ethylene, EIN3 is quickly degraded through a ubiquitin/proteasome
      pathway mediated by two F box proteins, EBF1 and EBF2. Plants containing
      mutations in either gene show enhanced ethylene response by stabilizing EIN3,
      whereas efb1 efb2 double mutants show constitutive ethylene phenotypes. Plants
      overexpressing either F box gene display ethylene insensitivity and
      destabilization of EIN3 protein. These results reveal that a ubiquitin/proteasome
      pathway negatively regulates ethylene responses by targeting EIN3 for
      degradation, and pinpoint EIN3 regulation as the key step in the response to
      ethylene.

PMID- 14675533
TI  - EIN3-dependent regulation of plant ethylene hormone signaling by two arabidopsis
      F box proteins: EBF1 and EBF2.
AB  - The plant hormone ethylene regulates a wide range of developmental processes and
      the response of plants to stress and pathogens. Genetic studies in Arabidopsis
      led to a partial elucidation of the mechanisms of ethylene action. Ethylene
      signal transduction initiates with ethylene binding at a family of ethylene
      receptors and terminates in a transcription cascade involving the EIN3/EIL and
      ERF families of plant-specific transcription factors. Here, we identify two
      Arabidopsis F box proteins called EBF1 and EBF2 that interact physically with
      EIN3/EIL transcription factors. EBF1 overexpression results in plants insensitive
      to ethylene. In contrast, plants carrying the ebf1 and ebf2 mutations display a
      constitutive ethylene response and accumulate the EIN3 protein in the absence of
      the hormone. Our work places EBF1 and EBF2 within the genetic framework of the
      ethylene-response pathway and supports a model in which ethylene action depends
      on EIN3 protein stabilization.

PMID- 14675534
TI  - Drosophila PAR-1 and 14-3-3 inhibit Bazooka/PAR-3 to establish complementary
      cortical domains in polarized cells.
AB  - PAR-1 kinases are required for polarity in diverse cell types, such as epithelial
      cells, where they localize laterally. PAR-1 activity is believed to be transduced
      by binding of 14-3-3 proteins to its phosphorylated substrates, but the relevant
      targets are unknown. We show that PAR-1 phosphorylates Bazooka/PAR-3 on two
      conserved serines to generate 14-3-3 binding sites. This inhibits formation of
      the Bazooka/PAR-6/aPKC complex by blocking Bazooka oligomerization and binding to
      aPKC. In epithelia, this complex localizes apically and defines the apical
      membrane, whereas Bazooka lacking PAR-1 phosphorylation/14-3-3 binding sites
      forms ectopic lateral complexes. Lateral exclusion by PAR-1/14-3-3 cooperates
      with apical anchoring by Crumbs/Stardust to restrict Bazooka localization, and
      loss of both pathways disrupts epithelial polarity. PAR-1 also excludes Bazooka
      from the posterior of the oocyte, and disruption of this regulation causes
      anterior-posterior polarity defects. Thus, antagonism of Bazooka by PAR-1/14-3-3
      may represent a general mechanism for establishing complementary cortical domains
      in polarized cells.

PMID- 14675535
TI  - The bacterial cytoskeleton: an intermediate filament-like function in cell shape.
AB  - Various cell shapes are encountered in the prokaryotic world, but how they are
      achieved is poorly understood. Intermediate filaments (IFs) of the eukaryotic
      cytoskeleton play an important role in cell shape in higher organisms. No such
      filaments have been found in prokaryotes. Here, we describe a bacterial
      equivalent to IF proteins, named crescentin, whose cytoskeletal function is
      required for the vibrioid and helical shapes of Caulobacter crescentus. Without
      crescentin, the cells adopt a straight-rod morphology. Crescentin has
      characteristic features of IF proteins including the ability to assemble into
      filaments in vitro without energy or cofactor requirements. In vivo, crescentin
      forms a helical structure that colocalizes with the inner cell curvatures beneath
      the cytoplasmic membrane. We propose that IF-like filaments of crescentin
      assemble into a helical structure, which by applying its geometry to the cell,
      generates a vibrioid or helical cell shape depending on the length of the cell.

PMID- 14675536
TI  - O-GlcNAc modification is an endogenous inhibitor of the proteasome.
AB  - The ubiquitin proteasome system classically selects its substrates for
      degradation by tagging them with ubiquitin. Here, we describe another means of
      controlling proteasome function in a global manner. The 26S proteasome can be
      inhibited by modification with the enzyme, O-GlcNAc transferase (OGT). This
      reversible modification of the proteasome inhibits the proteolysis of the
      transcription factor Sp1 and a hydrophobic peptide through inhibition of the
      ATPase activity of 26S proteasomes. The Rpt2 ATPase in the mammalian proteasome
      19S cap is modified by O-GlcNAc in vitro and in vivo and as its modification
      increases, proteasome function decreases. This mechanism may couple proteasomes
      to the general metabolic state of the cell. The O-GlcNAc modification of
      proteasomes may allow the organism to respond to its metabolic needs by
      controlling the availability of amino acids and regulatory proteins.

PMID- 14675537
TI  - The deacetylase HDAC6 regulates aggresome formation and cell viability in
      response to misfolded protein stress.
AB  - The efficient clearance of cytotoxic misfolded protein aggregates is critical for
      cell survival. Misfolded protein aggregates are transported and removed from the
      cytoplasm by dynein motors via the microtubule network to a novel organelle
      termed the aggresome where they are processed. However, the means by which dynein
      motors recognize misfolded protein cargo, and the cellular factors that regulate
      aggresome formation, remain unknown. We have discovered that HDAC6, a microtubule
      associated deacetylase, is a component of the aggresome. We demonstrate that
      HDAC6 has the capacity to bind both polyubiquitinated misfolded proteins and
      dynein motors, thereby acting to recruit misfolded protein cargo to dynein motors
      for transport to aggresomes. Indeed, cells deficient in HDAC6 fail to clear
      misfolded protein aggregates from the cytoplasm, cannot form aggresomes properly,
      and are hypersensitive to the accumulation of misfolded proteins. These findings
      identify HDAC6 as a crucial player in the cellular management of misfolded
      protein-induced stress.

PMID- 14675538
TI  - Ribosome loading onto the mRNA cap is driven by conformational coupling between
      eIF4G and eIF4E.
AB  - The eukaryotic initiation factor 4G (eIF4G) is the core of a multicomponent
      switch controlling gene expression at the level of translation initiation. It
      interacts with the small ribosomal subunit interacting protein, eIF3, and the
      eIF4E/cap-mRNA complex in order to load the ribosome onto mRNA during cap
      dependent translation. We describe the solution structure of the complex between
      yeast eIF4E/cap and eIF4G (393-490). Binding triggers a coupled folding
      transition of eIF4G (393-490) and the eIF4E N terminus resulting in a molecular
      bracelet whereby eIF4G (393-490) forms a right-handed helical ring that wraps
      around the N terminus of eIF4E. Cofolding allosterically enhances association of
      eIF4E with the cap and is required for maintenance of optimal growth and polysome
      distributions in vivo. Our data explain how mRNA, eIF4E, and eIF4G exists as a
      stable mRNP that may facilitate multiple rounds of ribosomal loading during
      translation initiation, a key determinant in the overall rate of protein
      synthesis.

PMID- 14675539
TI  - Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment
      of cofactors on a natural target promoter.
AB  - Transcriptional activation of a gene involves an orchestrated recruitment of
      components of the basal transcription machinery and intermediate factors,
      concomitant with an alteration in local chromatin structure generated by
      posttranslational modifications of histone tails and nucleosome remodeling. We
      provide here a comprehensive picture of events resulting in transcriptional
      activation of a gene, through evaluating the estrogen receptor-alpha (NR3A1)
      target pS2 gene promoter in MCF-7 cells. This description integrates chromatin
      remodeling with a kinetic evaluation of cyclical networks of association of 46
      transcription factors with the promoter, as determined by chromatin
      immunoprecipitation assays. We define the concept of a "transcriptional clock"
      that directs and achieves the sequential and combinatorial assembly of a
      transcriptionally productive complex on a promoter. Furthermore, the
      unanticipated findings of key roles for histone deacetylases and nucleosome
      remodeling complexes in limiting transcription implies that transcriptional
      activation is a cyclical process that requires both activating and repressive
      epigenetic processes.

PMID- 14675541
TI  - Proteins - reflecting the diversity of life.

PMID- 14675542
TI  - Mycobacterium tuberculosis: a model system for structural genomics.
AB  - Over the past five years, genomics has had a major impact on Mycobacterium
      tuberculosis research. With the publication of the sequences of two virulent
      strains (H37Rv and CDC1551) and three closely related sequences, M. tuberculosis
      is becoming a model system for proteomics and structural genomics initiatives.
      Together with the promise of structures of proteins with novel folds, high
      resolution structures of drug targets are providing the basis for rational
      inhibitor design, with the goal of the development of novel anti-tuberculars. In
      addition, this work is aiding scientists in the quest for an effective vaccine
      against this persistent pathogen.

PMID- 14675543
TI  - Molecular shredders: how proteasomes fulfill their role.
AB  - The 20S proteasome is a large, cylinder-shaped protease that is found in all
      domains of life and plays a crucial role in cellular protein turnover. It has
      multiple catalytic centers located within the hollow cavity of a molecular cage.
      This architecture prevents unwanted degradation of endogenous proteins and
      promotes processive degradation of substrates by restricting the dissociation of
      partially digested polypeptides. Although this kind of self-compartmentalization
      is generally conserved, the proteasomes of bacteria, archaea and eukaryotes show
      many differences in architecture, subunit composition and regulation. The
      structure of the 20S proteasome and its inherent role in the regulation of
      proteasome function are gradually being elucidated.

PMID- 14675544
TI  - Pathological and functional amyloid formation orchestrated by the secretory
      pathway.
AB  - Amyloidogenesis has historically been associated with pathology in a class of
      neurodegenerative diseases known as amyloid diseases. Recent studies have shown
      that proteolysis by furin during secretion initiates both variant gelsolin
      amyloidogenesis, associated with the disease familial amyloidosis of Finnish
      type, and Pmel17 fiber formation, which is necessary for the functional
      biogenesis of melanosomes. Proteolysis combined with organelle-dependent
      environment changes orchestrate amyloidogenesis associated with both pathological
      processes and a functional pathway.

PMID- 14675545
TI  - The low-density lipoprotein receptor: ligands, debates and lore.
AB  - Like pieces belonging to a large mosaic, the structures of low-density
      lipoprotein receptor (LDL-R) modules have been elucidated one by one in recent
      years. LDL-Rs localized on hepatocytes play an important role in removing
      cholesterol-transporting LDL particles from the plasma by receptor-mediated
      endocytosis. Key steps in this process involve the LDL-R binding LDL at neutral
      pH at the cell surface and, after internalization, releasing it again at acidic
      pH in the endosomes. How the modules of the LDL-R might interact within the
      intact receptor to carry out ligand binding and release has been revealed by the
      recent crystal structure of the extracellular domain of the LDL-R.

PMID- 14675546
TI  - Cadherin-mediated cell-cell adhesion: sticking together as a family.
AB  - The cadherins comprise a family of single-pass transmembrane proteins critical
      for cell-cell adhesion in vertebrates and invertebrates. The recently determined
      structure of the whole ectodomain from C-cadherin suggests that the adhesion of
      cadherins presented by juxtaposed cells is mediated by a strand-swapped dimer in
      which core hydrophobic elements are exchanged between the partner molecules.
      Sequence analysis suggests that several cadherin subfamilies share this adhesive
      mechanism. Recent work has shed new light on the molecular basis of cadherin
      adhesion, although understanding the specificity of these interactions remains a
      major challenge.

PMID- 14675547
TI  - SET domains and histone methylation.
AB  - The realisation that SET domains, which are found in numerous proteins involved
      in chromatin regulation, catalyse the methylation of lysine residues has led to
      intense interest in their cellular, biochemical and structural properties. The
      structures of five SET domain proteins have been reported over the past year. SET
      domains possess a novel fold, and use adjacent domains for both structural
      stabilisation and the completion of their active sites. The cofactor S-adenosyl-L
      methionine and peptide substrates bind on opposite faces of the SET domain.
      Remarkably, the sidechain of the target lysine approaches the transferred methyl
      group through a narrow channel that passes through the middle of the domain.

PMID- 14675548
TI  - Catalysis and regulation - from structure to function.

PMID- 14675549
TI  - Sub-Angstrom resolution enzyme X-ray structures: is seeing believing?
AB  - Recent technical advances in crystallographic analysis, particularly highly
      focused and high brilliance synchrotron beam lines, have significantly improved
      the resolutions that are attainable for many macromolecular crystal structures.
      The Protein Data Bank (http://www.rcsb.org/pdb/) contains an increasing number of
      atomic resolution structures, which are providing a wealth of structural
      information that was not previously visible in lower resolution electron density
      maps. Here, we review the importance of visualizing hydrogen atoms and multiple
      sidechain conformations or anisotropy, as well as substrate strain, at sub
      Angstrom resolution. The additional structural features that are visible in the
      electron density maps as a result of atomic resolution data provide a better
      understanding of the catalytic mechanisms of cholesterol oxidase, ribonuclease A,
      beta-lactamase, serine proteases, triosephosphate isomerase and endoglucanase.

PMID- 14675550
TI  - The positions of radical intermediates in the active sites of adenosylcobalamin
      dependent enzymes.
AB  - The radical intermediates generated during the catalytic cycles of
      adenosylcobalamin-dependent enzymes occur in pairs. The positions of radicals
      residing on the cofactor, substrate or protein, relative to the position of the
      low-spin Co(2+) from the cob(II)alamin intermediate, can be extracted from
      electron paramagnetic resonance (EPR) spectra of the spin-coupled pairs. Examples
      of radical-Co(2+) pairs that span a range of interspin distances from 3 to 13A
      have been presented. Interspin distances greater than 5A require motion of one or
      more of the participating species. EPR spectroscopy provides a convenient means
      to determine the structures of these transient intermediates.

PMID- 14675551
TI  - Structure and mechanism of bacterial dehalogenases: different ways to cleave a
      carbon-halogen bond.
AB  - The dehalogenases make use of fundamentally different strategies to cleave carbon
      halogen bonds. The structurally characterized haloalkane dehalogenases, haloacid
      dehalogenases and 4-chlorobenzoate-coenzyme A dehalogenases use substitution
      mechanisms that proceed via a covalent aspartyl intermediate. Recent X-ray
      crystallographic analysis of a haloalcohol dehalogenase and a trans-3
      chloroacrylic acid dehalogenase has provided detailed insight into a different
      intramolecular substitution mechanism and a hydratase-like mechanism,
      respectively. The available information on the various dehalogenases supports
      different views on the possible evolutionary origins of their activities.

PMID- 14675552
TI  - Catalysis by nucleoside hydrolases.
AB  - Nucleoside hydrolases cleave the N-glycosidic bond of ribonucleosides. Because of
      their vital role in the protozoan purine salvage pathway, nucleoside hydrolases
      from parasitic protozoa in particular have been studied extensively by X-ray
      crystallography, kinetic methods and site-directed mutagenesis. An elaborate
      network of conserved interactions between the metalloenzyme and the ribose
      enables steric and electrostatic stabilisation of the oxocarbenium-ion-like
      transition state. Activation of the leaving group by protonation before the
      formation of the transition state is a recurring catalytic strategy of enzymes
      that cleave N-glycosidic bonds. However, the mechanisms underlying leaving group
      activation are still the subject of debate for the nucleoside hydrolases.

PMID- 14675553
TI  - Structural biology of enzymes of the thiamin biosynthesis pathway.
AB  - Thiamin pyrophosphate is an essential cofactor of carbohydrate and branched-chain
      amino acid metabolism. Although its mechanistic role is well studied, the
      biosynthesis of thiamin has only recently been understood. Thiamin biosynthesis
      in Escherichia coli and Bacillus subtilis show some similarities, but diverge at
      key steps of thiazole formation. The biosynthesis of thiamin in eukaryotes is at
      a very early stage of understanding. Structural and mechanistic studies on
      thiamin biosynthetic enzymes have played a key role in increasing our
      understanding of thiamin pyrophosphate biosynthesis and have revealed unexpected
      evolutionary ties.

PMID- 14675554
TI  - The role of dynamics in allosteric regulation.
AB  - The biomolecular conformational changes often associated with allostery are, by
      definition, dynamic processes. Recent publications have disclosed the role of pre
      existing equilibria of conformational substates in this process. In addition, the
      role of dynamics as an entropic carrier of free energy of allostery has been
      investigated. Recent work thus shows that dynamics is pivotal to allostery, and
      that it constitutes much more than just the move from the 'T'-state to the 'R'
      state. Emerging computational studies have described the actual pathways of
      allosteric change.

PMID- 14675555
TI  - Prevention of fructose-induced hypertension by dietary vitamins.
AB  - Essential hypertension in humans may develop through a combination of genetic and
      environmental factors. Diet has long been under investigation as a potential
      effector of blood pressure. A diet high in sucrose or fructose can give rise to
      hyperlipidemia, insulin resistance and hypertension. Insulin resistance, glucose
      intolerance and oxidative stress are common features of hypertension. If glucose
      metabolism through the glycolytic pathway is impaired, as in insulin resistance,
      there will be a build-up of glyceraldehyde, glyceraldehyde-3-phosphate and
      dihydroxyacetone phosphate with further metabolism to methylglyoxal, a highly
      reactive ketoaldehyde. Excess aldehydes can bind sulfhydryl groups of membrane
      proteins, altering membrane calcium channels, increasing cytosolic free calcium,
      peripheral vascular resistance and blood pressure. The presence of reactive
      aldehydes can also lead to oxidative stress. Dietary management through lower
      sucrose or fructose intake and increased consumption of vitamins improves glucose
      metabolism, lowers tissue aldehydes, increases anti-oxidant capacity and may also
      prevent hypertension.

PMID- 14675556
TI  - In vitro analysis of human transplacental transport of desmopressin.
AB  - OBJECTIVE: Desmopressin (DDAVP) therapy may be required during pregnancy, but
      there are limited data about its safety. We wished to verify whether DDAVP is
      transported across the human placenta. METHODS: Using the in vitro human
      placental cotyledon perfusion model, we performed serial measurements of maternal
      and fetal DDAVP concentrations. After introducing the drug into the maternal
      circulation at estimated baseline therapeutic (30 pg/ml) and supratherapeutic
      (16,000 and 60,000 pg/ml) concentrations, we measured the rate of transplacental
      drug transfer up to 2 h. RESULTS: There was no detectable transport of DDAVP at a
      30 pg/ml concentration, and the maternal drug concentration remained stable over
      time. At a much higher maternal concentration of 60,000 pg/ml, the mean peak
      fetal DDAVP concentration was 2990 pg/ml, equivalent to 4.8% of the baseline
      maternal concentration. CONCLUSION: At a therapeutic maternal drug concentration,
      DDAVP does not appear to cross the placenta within detectable limits. At much
      higher drug concentrations, DDAVP may cross the placenta in a small amount.
      Future in vitro clinical studies should attempt to reproduce these findings.

PMID- 14675557
TI  - Development of an ultrasensitive enzyme immunoassay for human proadrenomedullin N
      terminal 20 peptide and direct measurement of two molecular forms of PAMP in
      plasma from healthy subjects and patients with cardiovascular disease.
AB  - OBJECTIVE: Proadrenomedullin N-terminal 20 peptide (PAMP) processed from an
      adrenomedullin precursor is a potent hypotensive peptide. It was anticipated that
      a mature form of PAMP (m-PAMP) and an intermediate PAMP-gly existed together in
      the blood. To measure concentrations of PAMPs in human plasma directly, we have
      developed a highly sensitive enzyme immunoassay (immune complex transfer enzyme
      immunoassay, ICT-EIA). DESIGN AND METHODS: PAMP was reacted simultaneously with
      2,4-dinitrophenyl (DNP)-biotinyl-bovine serum albumin (BSA)-anti-PAMP Fab'
      conjugate and anti-PAMP Fab'-beta-D-galactosidase conjugate. The immune complex
      that was formed was initially trapped onto a polystyrene bead coated with anti
      DNP IgG, and then transferred onto a second polystyrene bead coated with
      streptavidin. The resulting three-component complex was then assayed
      fluorometrically. RESULTS: The detection limits of ICT-EIA for both m-PAMP and
      PAMP-gly were 0.1 pmol/l with as little as 10 microl of plasma, and were a
      hundred times higher than with conventional radioimmunoassay (RIA). Using ICT
      EIA, we determined that the plasma concentrations of m-PAMP and PAMP-gly in 51
      healthy volunteers were 0.51 +/- 0.19 and 1.15 +/- 0.38 pmol/l (mean +/- SD),
      respectively. Both plasma m-PAMP and PAMP-gly concentrations in patients with a
      variety of diseases, including hypertension, heart failure, chronic renal
      failure, and hemodialysis, were significantly higher than those in healthy
      subjects. In addition, both plasma m-PAMP and PAMP-gly concentrations in patients
      with New York Heart Association (NYHA) class I-IV heart failure were increased in
      proportion to clinical severity. CONCLUSIONS: These sensitive and specific ICT
      EIAs may be used as a powerful tool for investigating the cardiovascular system
      in patients with heart failure.

PMID- 14675558
TI  - Cholesterol bound to hemoglobin in normal human erythrocytes: a new form of
      cholesterol in circulation?
AB  - OBJECTIVE: To study lipid fraction that is occasionally observed in red blood
      cell (RBC) hemolysate (supernatants from which membranes were separated). STUDY
      DESIGN: Plasma lipid profiles, cholesterol (Ch) and phospholipids (PL) in intact
      RBCs, RBC membranes and hemolysates were examined in young healthy male
      population in winter and summer. RESULTS: The RBC Ch and PL content was
      significantly higher than in membranes, both in winter and summer. The "excess"
      of cholesterol (associated with phospholipid) was bound to hemoglobin yielding Hb
      lipid adduct (Hb-Ch), the pools in the RBC membrane remaining virtually
      unaltered. Levels of hemoglobin-lipid complex (Hb-Ch), which were significantly
      higher in winter than in summer (30% and 19% of the total Hb, respectively),
      positively correlated with plasma HDL cholesterol levels. CONCLUSION: To our
      knowledge, this is the first demonstration of cholesterol binding to Hb. The
      results suggest influence of plasma lipoprotein metabolism on the formation of Hb
      Ch.

PMID- 14675559
TI  - A sol particle homogeneous immunoassay for measuring serum cystatin C.
AB  - OBJECTIVES: We have developed a sol particle immunoassay (SPIA) for measuring
      serum cystatin C, an endogenous marker of glomerular filtration rate (GFR).
      DESIGN AND METHODS: We used colloidal gold particles coated with anti-cystatin C
      antibodies. RESULTS: The assay was linear in the range 0.2 to 8 mg/L and showed
      good correlation between theoretical and obtained values. The within and between
      day coefficients of variation (CV) varied from 1.1 to 1.6% and 0.4 to 1.0%,
      respectively. Analytical recovery was 95.7 to 103.7%. No interference could be
      detected from bilirubin (up to 200 mg/L), hemoglobin (up to 3 g/L), chyle (up to
      5,000 FTU), rheumatoid factor (up to 1,000 IU/mL) or anticoagulants. Serum
      samples (n = 101), from which turbidity had been removed, were measured either
      with our assay or with Dako Cystatin C PET kits, using a Model 7070 Hitachi
      automatic clinical analyzer. Comparing these two methods, the calculated linear
      regression equation and the correlation coefficient were y = 0.986 x -0.153 and r
      = 0.995, respectively. CONCLUSIONS: Our new SPIA assay is a fully automated,
      homogeneous immunoassay that can readily be used in conjunction with various
      commercial analyzers that are currently available. The assay is sensitive,
      precise and suitable for clinical use and appears to offer advantages over other
      GFR markers such as creatinine.

PMID- 14675560
TI  - Solid phase measurements of antibody and lectin binding to xenogenic carbohydrate
      antigens.
AB  - OBJECTIVES: In future pig-to-man xenotransplantation it is important to master
      tools that identify potentially xenogenic alphagalactose (Galalpha) antigens in
      the doner tissue. DESIGN AND METHODS: We have measured the binding potentials of
      Galalpha detecting lectins and antibodies, including a naturally occurring
      subfraction from human serum, to Galalpha containing neoglycoproteins and mouse
      laminin that were immobilized on microtiter plates. RESULTS: Galalpha reactive
      antibodies with similar monosaccharide specificity have distinct structural
      preference for sugar ligands. Laminin and neoglycoproteins were treated with
      alpha-galactosidase and subsequently incubated with antibodies and lectins. The
      enzyme treatment was more deleterious on antibody binding than on lectin binding.
      CONCLUSION: Antibodies and lectins may bind to different galactose determinants
      on the glycoproteins. Two anti-Galalpha1 antibodies that both have been raised
      against glycans on rabbit red blood cells may recognize Galalpha-antigens with
      varying specificities. Binding results obtained after digestion with alpha
      galactosidase indicate that some xenoreactive Galalpha groups are not directly
      accessible for removal by the enzyme.

PMID- 14675561
TI  - Differential effects of lipid-lowering agents on human cholinesterases.
AB  - OBJECTIVES: Epidemiologic reports indicate that lipid-lowering agents (LLAs)
      protect against dementia. We hypothesized that LLAs might affect cholinergic
      systems. The effects of LLAs on the activity of cholinesterases were examined.
      DESIGN AND METHODS: Odds ratios and relative risks were calculated from clinical
      studies of LLAs and dementia and compared with their impacts on human
      cholinesterases. Representative LLAs were examined for their effects on the
      activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using
      Ellman's assay. RESULTS: Epidemiological studies, but not clinical trials, showed
      lower odds of dementia in patients taking "statins". Comparison of LLAs indicated
      that "statins" most consistently produced apparent protection. Individual
      "statins" showed differential cholinesterase inhibition. Lovastatin and
      simvastatin significantly inhibited butyrylcholinesterase, while mevastatin,
      pravastatin and the "non-statins" did not. None of the LLAs inhibited
      acetylcholinesterase. CONCLUSIONS: Some "statins" inhibit butyrylcholinesterase.
      This inhibition suggests a possible means whereby "statins" could protect against
      dementia.

PMID- 14675562
TI  - Which is more effective in the prevention of renal ischemia-reperfusion-induced
      oxidative injury in the early period in mice: interleukin (IL)-10 or anti-IL-12?
AB  - OBJECTIVES: Ischemia-reperfusion (I-R) injury induces production of reactive
      oxygen species (ROS) and some inflammatory mediators like tumor necrosis factor
      (TNF). We compared the effects of IL-10 and anti IL-12 antibody (Ab) on TNF-alpha
      production and oxidative stress markers. We also searched for which one, anti IL
      12 or IL-10, is superior in the prevention of I-R induced oxidative stress.
      DESIGN AND METHODS: The animals were divided into four groups: control (n = 5), I
      R (n = 5), I-R + IL-10 (n = 5), I-R + anti IL-12 Ab (n = 5). Mice were subjected
      to renal ischemia by clamping the left pedicle for 45 min, and were then
      reperfused for 1 h. RESULTS: Under conditions of IL-12 blockade and IL-10
      treatment, I-R-induced tissue TNF-alpha levels were significantly reduced (P <
      0.01). IL-10 treatment decreased I-R-induced thiobarbituric acid reactive
      substances (TBARS) and protein carbonyl content levels (P < 0.05). After IL-10
      treatment, decrease in tissue reduced glutathione (GSH) levels were prevented.
      Renal superoxide dismutase (SOD) and catalase (CAT) activities were observed to
      be decreased after I-R. IL-10 treatment increased both SOD and CAT activities
      over control values (P < 0.05). CONCLUSION: These data indicated that IL-10
      treatment may be more effective than anti-IL-12 treatment in the prevention of
      renal I-R-induced oxidative injury in the early period.

PMID- 14675563
TI  - Tumour-associated trypsin inhibitor, carcinoembryonic antigen and acute-phase
      reactant proteins CRP and alpha1-antitrypsin in patients with gastrointestinal
      malignancies.
AB  - OBJECTIVES: Elevated serum tumour-associated trypsin inhibitor (TATI) levels have
      been observed in association with malignancy or inflammation. The aim of our
      study was to evaluate the role of TATI in gastric and colorectal cancer. DESIGN
      AND METHODS: In preoperative serum samples, we measured TATI, carcinoembryonic
      antigen (CEA), C-reactive protein (CRP) and alpha(1)-antitrypsin (AAT). RESULTS:
      Elevated levels of TATI were observed in 50% and 41.7% of patients with gastric
      and colorectal cancer. Elevated levels of TATI were observed only in 8% of
      patients with benign gastrointestinal malignancies (92% specificity). Elevated
      levels of CEA were observed in 25% and 24.4% of patients, respectively. The total
      positivity of CEA and TATI (with at least one marker positive) was 62.5% and 57%,
      respectively. Spearman's test has shown a statistically significant correlation
      among serum TATI, CRP and AAT levels (P < 0.01). CONCLUSIONS: In gastrointestinal
      cancer, TATI can be used as a complementary tumour marker in addition to CEA.
      Regulation of TATI synthesis resembles that of acute-phase reactant proteins.

PMID- 14675564
TI  - [3H]PK11195 binding sites in human neutrophils: effect of fMLP stimulation and
      modulation in rheumatic diseases.
AB  - OBJECTIVE: The objectives of this study were to evaluate the [3H]PK11195 binding
      parameters in a model of acute inflammation, the N-formylmethionine-leucine
      phenylalanine (fMLP)-stimulated neutrophil cell membranes, and to analyze if
      alterations of peripheral-type benzodiazepine receptor (PBR) characteristics
      occurred in neutrophil cell membranes of patients affected by osteoarthritis
      (OA), rheumatoid arthritis (RA), and psoriasic arthritis (PA). DESIGN AND
      METHODS: Neutrophils were obtained from 15 patients with OA, 15 patients with RA,
      and 15 patients with PA. fMLP stimulation was performed to aliquots of
      neutrophils from six healthy individuals. Evaluation of kinetic parameters of PBR
      was performed using [3H]PK11195, as specific radioligand compared with 15 healthy
      volunteers. RESULTS: The results showed a significant decrease of Kd and Bmax in
      fMLP-stimulated neutrophil membranes. Moreover, an increase of PBR binding sites
      and affinity value was observed in neutrophils membranes from PA patients.
      CONCLUSIONS: Our data suggested a fMLP modulation on [3H]PK11195 binding in human
      neutrophils. Moreover, our results showed an up-regulation of PBR in neutrophils
      of PA patients.

PMID- 14675565
TI  - Erythrocyte zinc and carbonic anhydrase levels in nondialyzed chronic kidney
      disease patients.
AB  - OBJECTIVE: The aim of the present study was to determine the erythrocyte CAI and
      CAII concentrations in nondialyzed chronic kidney disease patients, and observe
      the relationship with acidosis, zinc, anemia, and iron supplementation. METHODS:
      Erythrocyte CA concentrations were measured in nondialyzed patients (n = 38)
      using enzyme-linked immunosorbent assays (ELISA). The zinc concentration was
      determined by atomic absorption spectrophotometer. RESULTS AND CONCLUSIONS: The
      CA levels were observed to be increased in the patients. The mean erythrocyte
      zinc concentration was also high and the levels of zinc in plasma were baseline
      values. Correlation was found between CAI and erythrocytes Zn (r = 0.46; P =
      0.003), but there was no correlation with ferritin or pH and bicarbonate. The CA
      levels did not change after iron supplementation, but the zinc erythrocyte levels
      were reduced. It is concluded that the CA erythrocyte concentration in CKD
      patients is increased but this cannot be explained by iron deficiency or
      acidosis.

PMID- 14675566
TI  - Positive correlation between in vivo oxidized LDL and LDL immune complexes.
AB  - OBJECTIVES: To investigate the possible relationship between oxidized low-density
      lipoprotein (ox-LDL) and LDL immune complexes (IC). METHODS: Both LDL-IC and ox
      LDL were detected by sandwich ELISA. The levels were also studied in 60 patients
      with coronary heart disease (CHD) and 50 control subjects. RESULTS: Compared to
      controls, both the plasma ox-LDL concentrations (595.5 +/- 194.8 vs. 440.3 +/-
      175.0 microg/l, P < 0.001) and LDL-IC levels (2.74 +/- 0.73 vs. 1.38 +/- 0.78 AU,
      P < 0.001) in the patients with CHD were significantly increased. The
      relationships between LDL-IC, ox-LDL levels, and other lipid parameters in all
      the studied subjects (n = 100) were analyzed. LDL-IC levels were positively
      correlated with TC, TG, LDL-C, lipoprotein(a) [Lp(a)], and apolipoprotein B
      (apoB) concentration, while negatively correlated with apoA1 concentration,
      respectively. Similarly, ox-LDL levels were also found positively correlated with
      TC, LDL-C, and apoB concentrations, respectively. Furthermore, a significantly
      positive correlation between ox-LDL and LDL-IC levels was found (r = 0.313, P <
      0.005). CONCLUSION: In vivo oxidized LDL positively correlates with circulating
      levels of LDL immune complexes.

PMID- 14675567
TI  - Serum levels of neural protein S-100B in phenylketonuria.
AB  - BACKGROUND: Serum neural protein S-100B concentration is considered as a marker
      of CNS lesions. Phenylketonuria (PKU) is a metabolic disorder characterized by
      high phenylalanine (Phe) levels in blood and foci of myelin absence in the CNS of
      untreated patients. AIM: To evaluate S-100B blood levels in PKU patients.
      METHODS: Twenty-five (N = 25) PKU patients of comparable age, who were diagnosed
      by neonatal screening and "followed up" in our Inborn Error of Metabolism
      Department, were divided into two groups: group A (N = 13) with almost normal Phe
      levels and group B (N = 12) "off diet" with high Phe concentrations. Their MRI
      examinations were normal 12-14 months before the beginning of the study. Twenty
      three (N = 23) healthy children were the controls. Serum S-100B levels, measured
      with an immunoluminometric assay, were greatly elevated in the group B (0.48 +/-
      0.6 microg/l) as compared to those of group A (0.16 +/- 0.4 microg/l, P < 0.001)
      and controls (0.10 +/- 0.02, P < 0.001). Positive correlation was found between S
      100B and Phe blood concentration (r = 0.46, P < 0.01). Foci of myelin absence in
      MRIs were observed in 1/13 of group A and in 10/12 of group B at the end of this
      study. CONCLUSIONS: (a) Serum S-100B protein level, for the first time evaluated
      in PKU, was positively correlated with Phe blood level in PKU patients. (b) S
      100B blood estimation could be a useful peripheral marker of CNS lesions in
      patients with demyelinated disease such as PKU.

PMID- 14675569
TI  - Usefulness of statin drugs in protecting against atrial fibrillation in patients
      with coronary artery disease.
AB  - Atrial fibrillation (AF) is prevalent in the elderly, in patients with
      hypertension, and in patients with coronary artery disease (CAD). We hypothesized
      that statin therapy might be effective in preventing AF in patients with CAD and
      examined this hypothesis in a sample of patients with chronic stable CAD without
      AF, followed prospectively at a large outpatient cardiology practice. The
      association between statin use and the risk of developing AF was examined
      univariately and then with adjustment for potential confounding factors. Four
      hundred forty-nine men and women between the ages of 40 and 87 years were
      followed for an average of 5 years. Fifty-two patients (12%) developed AF during
      follow-up. Statin therapy was used by 59% of the patients during the study period
      and was associated with a significantly reduced risk of developing AF (crude odds
      ratio, 0.48, 95% confidence interval 0.28 to 0.83). This association remained
      significant after adjustment for potential confounders, including age,
      hypertension, left ventricular systolic function, occurrence of heart failure or
      acute ischemic events, and baseline cholesterol and changes in cholesterol levels
      (adjusted odds ratio 0.37, 95% confidence interval 0.18 to 0.76). Use of statins
      in patients with chronic stable CAD appears to be protective against AF. The
      underlying mechanism for this effect is unknown but appears to be independent of
      the reduction in serum cholesterol levels.

PMID- 14675570
TI  - Feasibility and safety of transeophageal atrial pacing stress echocardiography in
      patients with known or suspected coronary artery disease.
AB  - To investigate the feasibility and safety of the transesophageal atrial pacing
      stress test combined with echocardiography (TAPSE) 1,727 TAPSE tests were
      performed on 1,641 patients consecutively referred to our echocardiographic
      laboratory for nonexercise stress testing (1,319 men; mean age 60 +/- 9 years;
      34% of whom were outpatients). Wall motion abnormalities were present at baseline
      echocardiography in 975 cases (56%). TAPSE was feasible in 1,648 cases (95.4%).
      It was not feasible in 79 patients due to failure of positioning the transnasal
      catheter (n=11), the patient's intolerance of esophageal stimulation (n=24),
      failure to obtain any or stable atrial capture (n=36), or because the
      echocardiogram could not be evaluated at the peak of the test (n=8). TAPSE was
      diagnostic in 1,584 cases (96% of the feasible tests, 92% of all attempts). TAPSE
      was nondiagnostic in 64 cases (4% of the feasible tests) due to second-degree
      atrioventricular type I block resistance to atropine administration with failure
      to achieve 85% of the age-predicted maximum heart rate (n=59) or due to side
      effects, such as arrhythmias (n=3) or hypertension (n=2), which required
      premature interruption of the test. There were no major complications (death,
      myocardial infarction, or life-threatening arrhythmias). There were 28 instances
      of minor complications that comprised transient arrhythmias, including atrial
      fibrillation (n=8), paroxysmal supraventricular tachycardia (n=6), automatic
      atrial tachycardia (n=1), sinus arrest (n=1), atrioventricular junctional rhythm
      (n=2), ectopic atrial rhythm (n=2), nonsustained ventricular tachycardia (maximum
      6 beats, n=3), hypotension (n=1), and hypertension (n=4) leading to interruption
      of the test. Only 5 complications hampered a diagnostic result, whereas 18
      occurred during or after a positive test and 5 during a negative, but diagnostic,
      test. Thus, TAPSE is a highly feasible and very safe stress test. It gives high
      percentage of diagnostic tests and may represent a valid alternative to
      pharmacologic stressors.

PMID- 14675571
TI  - Cut-off value of coronary flow velocity reserve by transthoracic Doppler
      echocardiography for diagnosis of significant left anterior descending artery
      stenosis in patients with coronary risk factors.
AB  - The purpose of this study was to evaluate the adequate cut-off value of coronary
      flow velocity reserve (CFVR) with transthoracic Doppler echocardiography for
      diagnoses of significant left anterior descending (LAD) artery stenosis in a
      large study population with various coronary risk factors. CFVR, which has been
      used for evaluation of significant coronary artery stenosis, can be reduced
      despite angiographically normal coronary arteries in patients with various
      coronary risk factors. However, the adequate cut-off value of CFVR for diagnosing
      significant LAD stenosis has not been fully established in patients with coronary
      risk factors. We examined 138 consecutive patients who underwent coronary
      angiography. Clinical histories of coronary risk factors were determined from
      interviews or medical records. CFVR assessment in the LAD artery by transthoracic
      Doppler echocardiography was performed in all patients. Of the 138 patients, 30
      had significant stenosis, and the remainder had no stenotic lesions in the LAD
      artery. Receiver-operating characteristic curves for detection of significant LAD
      stenosis showed that a cut-off value of <2.0 was extremely precise. A cut-off
      value <2.0 of CFVR had a sensitivity of 90%, a specificity of 93%, a positive
      predictive value of 77%, and a negative predictive value of 97% for the presence
      of significant LAD stenosis. A cut-off value <2.0 of CFVR by transthoracic
      Doppler echocardiography was adequate for the diagnosis of significant LAD
      stenosis in a population that included patients with coronary risk factors.

PMID- 14675572
TI  - Response of the left anterior descending coronary artery to acetylcholine in
      patients with chest pain and angiographically normal coronary arteries.
AB  - Because atherosclerotic plaque burden affects the likelihood of plaque rupture,
      it is important to determine the presence and extent of atherosclerotic plaque.
      We hypothesized that endothelial dysfunction becomes more prominent with
      development of atherosclerotic plaque; therefore, we examined the relation
      between coronary endothelial dysfunction and the presence of atherosclerotic
      plaque. In 36 patients with normal coronary arteries, acetylcholine (ACh; 3 and
      30 microg/min) and nitroglycerin were infused into the left coronary ostium, and
      the diameter of the left anterior descending (LAD) coronary artery was
      quantitatively measured in response to each drug. The plaque burden was measured
      in the same segment using intravascular ultrasonography. The plaque burden was
      31.2 +/- 2.1% and correlated inversely with changes in coronary diameter induced
      by 3 microg/min of ACh (r = -0.754, p <0.0001), 30 microg/min of ACh (r = -0.552,
      p = 0.0005), and nitroglycerin (r = -0.531, p = 0.0009). Multivariate regression
      analysis showed that the change in coronary diameter induced by 3 microg/min of
      ACh was associated with plaque burden, independent of the effects of
      nitroglycerin-induced dilation. Receiver-operating characteristics analysis
      demonstrated that a cut-off value for the change in coronary diameter induced by
      3 microg/min of ACh for predicting a plaque burden of >30% was 0%, with a
      sensitivity of 0.82 and a specificity of 0.95. These findings suggest that
      coronary endothelial dysfunction is correlated with atherosclerotic plaque
      burden, indicating that atherosclerotic plaque may be detected based on coronary
      endothelial function as assessed by low-dose ACh infusion.

PMID- 14675573
TI  - Usefulness of residual percent plaque area after percutaneous coronary
      intervention in predicting peristent positive remodeling.
AB  - The aim of this study was to determine whether a stented coronary artery might be
      positively remodeled, which factors predict this phenomenon, and whether positive
      remodeling has an association with late outcome. The study population consisted
      of 230 lesions in 230 patients who received bare-metal stents. We performed
      intravascular ultrasound analyses before and after the procedure and at follow
      up. An artery was defined as positively remodeled if the ratio of follow-up to
      postvessel area was > or =1.1. The following indexes were calculated and defined:
      (1) late loss = postluminal area - follow-up luminal area; (2) percent plaque
      area = ([vessel area - luminal area]/vessel area x 100), (3) Delta% plaque area =
      follow-up percent plaque area - postprocedure percent plaque area. Although late
      loss in the positively remodeled group was significantly smaller than that in the
      nonremodeled group (p<0.05), d% plaque area in the former group was significantly
      larger than that in the latter group (p<0.05). The rate of restenosis in the
      positive remodeling group (16.4%) was significantly lower than that in the
      nonremodeling group (28.2%) (p<0.05). In multivariate analysis, postprocedure
      percent plaque area was the only powerful independent predictor for peristent
      positive remodeling and was inversely associated with this phenomenon in both
      groups (odds ratio 0.944, 95% confidence interval 0.914 to 0.975, p=0.0004). This
      study indicates that postprocedure percent plaque area could predict the
      occurrence of peristent positive remodeling at follow-up and that this phenomenon
      might influence late outcome.

PMID- 14675574
TI  - A comparative study of rotational atherectomy in acute and stable coronary
      syndromes in the modern era.
AB  - Percutaneous rotational coronary atherectomy (PRCA) is commonly used in the
      percutaneous treatment of diffuse, calcified coronary lesions in stable coronary
      syndromes (SCSs) and facilitates successful delivery and deployment of balloons
      and stents. Early experience with PRCA cautioned its use in acute coronary
      syndromes (ACSs). However, the evolution of the PRCA technique and improved
      antiplatelet pharmacotherapy has broadened its use in ACSs also. A total of 1,112
      consecutive patients with an ACS (n=269) or SCS (n=843) who underwent PRCA of
      1,483 lesions were examined retrospectively to evaluate the angiographic and
      short-term clinical outcomes. Troponin-I was elevated in 33.3% of the ACS group
      and in 0.6% of the SCS group at baseline (p<0.001). Angiographic complications
      occurred more frequently in the ACS group (18.6% vs 13.1%, p=0.02). There was no
      difference in major complications between the groups (ACS 1.1% vs SCS 0.8%;
      p=0.44). The incidence of any periprocedural creatinine kinase-MB elevation was
      17.1% versus 18.9% (p=NS) and 30-day major adverse cardiac events (death,
      disabling stroke, creatine kinase-MB >3 times the upper limit of normal, urgent
      revascularization) was 5.9% versus 4.6% (p=NS) when comparing the ACS and SCS
      groups, respectively. With current techniques and antiplatelet therapy, PRCA can
      be safely performed in ACSs when lesion morphology dictates, with outcomes
      comparable to that achieved in SCSs. Although angiographic complications occurred
      more frequently in the ACS group, this did not result in a significantly higher
      incidence of postprocedural myonecrosis or 30-day major adverse cardiac events.

PMID- 14675575
TI  - Comparison of the angiographic outcomes after beta versus gamma vascular
      brachytherapy for treatment of in-stent restenosis.
AB  - This study was designed to compare the angiographic outcomes of beta versus gamma
      vascular brachytherapy (VBT). We reviewed the angiographic results of 636 lesions
      (212 that underwent beta and 212 that underwent gamma VBT, and 212 that received
      placebo) with native coronary in-stent restenosis matched for lesion length,
      vessel size, preprocedure minimum lumen diameter (MLD), and time to angiographic
      follow-up in the various randomized clinical trials and studies. Baseline lesion
      complexity was similar in these 3 groups. Final MLD was smaller in the beta VBT
      group than in the gamma VBT or placebo group. At follow-up, beta and gamma VBT
      significantly reduced both angiographic restenosis (34.4% for beta VBT, 26.4% for
      gamma VBT, and 50.9% in the placebo group; p <0.0001) and recurrent lesion length
      (9.2 mm for beta VBT, 8.4 mm for gamma VBT, and 15.5 mm placebo, p <0.0001)
      compared with placebo. Gamma VBT was associated with a greater reduction in
      restenosis outside the stent than beta VBT. By multivariable analysis,
      independent angiographic predictors of treated segment restenosis included beta
      or gamma VBT, lesion length, and vessel size. In matched lesions, beta and gamma
      VBT achieved similar reductions in treated segment restenosis and recurrent
      lesion length compared with placebo.

PMID- 14675576
TI  - Effect of coadministration of ezetimibe and simvastatin on high-sensitivity C
      reactive protein.
AB  - This study assessed the effect of ezetimibe coadministered with simvastatin on
      high-sensitivity C-reactive protein (hs-CRP) in patients with primary
      hypercholesterolemia. After dietary stabilization, a 2- to 12-week washout
      period, and a 4-week, single-blind, placebo lead-in period, patients with
      baseline low-density lipoprotein cholesterol > or =145 and < or =250 mg/dl and
      triglycerides < or =350 mg/dl were randomized to one of these daily treatments
      for 12 consecutive weeks: ezetimibe 10 mg; simvastatin monotherapy (10, 20, 40,
      or 80 mg); ezetimibe 10 mg plus simvastatin (10, 20, 40, or 80 mg); or placebo.
      The primary analysis was the change in hs-CRP for the pooled ezetimibe plus
      simvastatin versus simvastatin monotherapy groups. Ezetimibe plus simvastatin
      significantly reduced median hs-CRP levels compared with simvastatin monotherapy
      (-34.8% vs -18.2%, p<0.01), and incremental reductions were observed at each
      simvastatin dose level. Combination therapy-induced significant changes in
      individual lipid parameters did not explain the observed decreases in hs-CRP.
      Thus, ezetimibe coadministered with simvastatin resulted in significant
      incremental decreases in hs-CRP, possibly consistent with an additional anti
      inflammatory effect compared with simvastatin monotherapy.

PMID- 14675577
TI  - Sex-specific increase in the prevalence of atrial fibrillation (The Copenhagen
      City Heart Study).
AB  - Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia.
      It is a risk factor for stroke and premature death. We studied the temporal
      changes in the prevalence of AF from 1976 to 1994 in a random population aged 50
      to 89 years. The prevalence of AF, diagnosed from electrocardiograms (ECGs), was
      determined in 8,606 patients examined in 1976 to 1978, in 8,943 patients examined
      in 1981 to 1983, and in 6,733 subjects examined in 1991 to 1994. Changes in
      prevalence of AF were estimated by logistic regression analysis. In men, the age
      standardized prevalence of AF increased from 1.4% in 1976 to 1978 (odds ratio
      [OR] 1.0, reference) to 1.9% in 1981 to 1983 (OR 1.6, 95% confidence interval
      [CI] 1.1 to 2.1), and to 3.3% in 1991 to 1994 (OR 2.3, 95% CI 1.6 to 3.4,
      p<0.001, adjusted for age). In women, the prevalence of AF decreased from 1.5% in
      1976 to 1978 (OR 1.0, reference) to 1.0% in 1981 to 1983 (OR 0.7, 95% CI 0.5 to
      1.0), and to 1.1% in 1991 to 1994 (OR 0.7, 95% CI 0.5 to 1.0), although the
      overall decrease was not significant (p=0.11, adjusted for age). After adjusting
      for changes in comorbidity, body weight, and height, the increase in the
      prevalence of AF in men from 1976 to 1978 and from 1991 to 1994 remained
      significant (OR 1.9, 95% CI 1.3 to 2.8, p=0.002). Although unchanged in women,
      the prevalence of AF in men more than doubled from the 1970s to the 1990s. The
      factors responsible for this gender-specific increase in the prevalence of this
      common arrhythmia have yet to be identified.

PMID- 14675578
TI  - Usefulness of ST-segment elevation in lead aVR during tachycardia for determining
      the mechanism of narrow QRS complex tachycardia.
AB  - In the present study, we analyzed ST-segment elevation in lead aVR during
      tachycardia to differentiate the narrow QRS complex tachycardia. A total of 338
      12-lead electrocardiograms during narrow QRS complex tachycardia were analyzed.
      Each patient underwent a complete electrophysiologic study. There were 161
      episodes of atrioventricular nodal reentrant tachycardia (AVNRT), 165 episodes of
      atrioventricular reciprocating tachycardia (AVRT), and 12 episodes of atrial
      tachycardia (AT). The prevalence of aVR ST-segment elevation was 71% for AVRT,
      31% for AVNRT, and 16% for AT. For ST-T changes in different leads, logistic
      regression analysis showed aVR ST-segment elevation was the only significant
      factor to differentiate the types of narrow QRS complex tachycardia (p<0.001 for
      AVRT and AVNRT; p=0.02 for AVRT and AT). The sensitivity, specificity, and
      accuracy of aVR ST-segment elevation to differentiate AVRT from AVNRT and AT were
      71%, 70%, and 70%, respectively. Among 117 episodes of AVRT with aVR ST-segment
      elevation, there were 76 (65%) left side, 23 (20%) right side, 14 (12%) posterior
      septal, and 4 (3%) antero- and mid-septal accessory pathways (p=0.002). In
      conclusion, aVR ST-segment elevation during narrow QRS complex tachycardia favors
      the atrioventricular reentry through an accessory pathway as the mechanism of the
      tachycardia.

PMID- 14675579
TI  - Prediction of mortality in patients with right bundle branch block referred for
      pharmacologic stress echocardiography.
AB  - Right bundle branch block (RBBB) is independently associated with all-cause
      mortality in patients referred for noninvasive evaluation of coronary artery
      disease. However, further stratification of risk in these patients has not been
      specifically addressed. The aim of this study was to risk stratify patients with
      RBBB who were referred for stress echocardiography. The study population was
      comprised of 343 patients (267 men; age 66 +/- 9 years) with RBBB who underwent
      pharmacologic stress echocardiography (231 dipyridamole, 112 dobutamine) for
      evaluation of suspected or known coronary artery disease. Overall mortality was
      the only end point. Stress echocardiography was positive for ischemia in 109
      patients (32%). During follow-up (38 +/- 32 months), 36 deaths occurred. Seventy
      three patients underwent revascularization and were censored. Ischemia at stress
      echocardiography (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.5 to 5.5,
      p=0.002), left anterior fascicular block (LAFB) (HR 2.8, 95% CI 1.4 to 5.6, p =
      0.002), age >65 years (HR 2.1, 95% CI 1.0 to 4.3, p=0.047), and wall motion score
      index at rest (HR 2.5, 95% CI 1.0 to 6.5, p=0.057) were multivariate predictors
      of mortality. On the basis of stress echocardiographic result and presence and/or
      absence of LAFB, 3 levels of risk were identified: (1) low-risk, in cases of no
      ischemia and no LAFB (49% of the entire study population); (2) intermediate-risk,
      in cases of ischemia or LAFB only; and (3) high-risk, in cases of ischemia and
      LAFB. Clinical data, electrocardiography at rest, and stress echocardiographic
      results can provide effective stratification of risk in patients with RBBB.

PMID- 14675580
TI  - Usefulness of B-type natriuretic peptide in hypertensive patients with exertional
      dyspnea and normal left ventricular ejection fraction and correlation with new
      echocardiographic indexes of systolic and diastolic function.
AB  - B-type natriuretic peptide (BNP) levels increase in systolic heart failure (HF).
      However, the value of BNP in hypertensive patients with suspected diastolic HF
      (symptoms suggestive of HF but normal ejection fraction) and its relation to
      myocardial function in these patients is unclear. We prospectively studied 72
      ambulatory hypertensive subjects (40 women, mean age 58 +/- 8 years) with
      exertional dyspnea and ejection fraction > or =50%. Diastolic function was
      evaluated with transmitral and pulmonary venous Doppler, mitral annular
      velocities (pulsed-wave tissue Doppler), and flow propagation velocity (color M
      mode). Systolic function was assessed with strain and strain rate derived from
      color tissue Doppler imaging. BNP was related to myocardial function and the
      presence or absence of global diastolic dysfunction. By conventional Doppler
      criteria, 34 patients had normal left ventricular diastolic function and 38 had
      isolated diastolic dysfunction. BNP values were higher in patients with diastolic
      dysfunction (46 +/- 48 vs 20 +/- 20 pg/ml, p=0.004) and were related
      independently to blood pressure, systolic strain rate, left atrial function
      (p<0.01 for all), and age (p=0.015). Patients with diastolic dysfunction and
      pseudonormal filling had higher BNP levels compared with impaired relaxation (89
      +/- 47 vs 35 +/- 42 pg/ml, p=0.001). However, 79% of patients with diastolic
      dysfunction had BNP levels within the normal range. We conclude that in
      ambulatory hypertensive patients with symptoms suggestive of mild HF and normal
      ejection fraction, BNP is related to atrial and ventricular systolic parameters,
      blood pressure, and age. Although elevated in the presence of diastolic
      dysfunction, the BNP level mostly is in the normal range and, therefore, has
      limited diagnostic value in stable patients with suspected diastolic HF.

PMID- 14675581
TI  - Improving the utility of the nocturnal hypertension definition by using absolute
      sleep blood pressure rather than the "dipping" proportion.

PMID- 14675582
TI  - Prognostic significance of an elevated creatine kinase in the absence of an
      elevated troponin I during an acute coronary syndrome.
AB  - In patients with troponin-negative acute coronary syndromes, creatine kinase (CK)
      MB elevation predicts a significantly higher risk of death and major acute
      cardiac events compared with CK-MB negative patients. This risk is accentuated in
      troponin-negative, CK-MB positive patients who do not demonstrate ST elevation by
      electrocardiogram.

PMID- 14675583
TI  - Prognostic significance of transient no-reflow during primary percutaneous
      coronary intervention for ST-elevation acute myocardial infarction.
AB  - We found that of 1,192 patients who underwent primary percutaneous coronary
      intervention and who had final Thrombolysis In Myocardial Infarction grade 3 flow
      at the conclusion of the procedure, transient no-reflow occurred in 16 patients
      (1.3%). Compared with patients without transient no-reflow during the procedure,
      those with transient no-reflow had higher in-hospital (2% vs 13%, p=0.04) and 6
      month mortality (3% vs 31%, adjusted odds ratio 5.4, 95% confidence interval 1.01
      to 29.0, p=0.0001).

PMID- 14675584
TI  - A propensity score-matched cohort study of the effect of statins, mainly
      fluvastatin, on the occurrence of acute myocardial infarction.
AB  - This investigation quantified the effect of statins on acute myocardial
      infarction (AMI) in an observational setting where fluvastatin represented most
      of the statin use. The study applied propensity scores to match statin initiators
      to statin noninitiators and followed them for the occurrence of AMI. Serum low
      density lipoprotein levels were reduced by statin therapy, and there were fewer
      incidents of AMI in statin initiators than in noninitiators.

PMID- 14675585
TI  - Variability of inotropic and chronotropic response during dobutamine stress
      echocardiography and possible implications for diagnostic accuracy.
AB  - Chronotropic and inotropic response patterns were assessed during dobutamine
      stress echocardiography. Three heart rate response patterns were noted:
      nonresponders (48% of patients), slow responders (30% of patients), and fast
      responders (21% of patients). There was no relation between heart rate and
      contractile response.

PMID- 14675586
TI  - Meta-analysis of randomized clinical trials on the usefulness of acetylcysteine
      for prevention of contrast nephropathy.
AB  - Multiple small studies of oral N-acetylcysteine for prevention of contrast
      nephropathy have been performed, demonstrating variable efficacy. We performed a
      meta-analysis of the randomized clinical trials to clarify the degree of benefit.

PMID- 14675587
TI  - Prognostic value of cardiac autonomic neuropathy independent and incremental to
      perfusion defects in patients with diabetes and suspected coronary artery
      disease.
AB  - We investigated the prognostic value of cardiac autonomic neuropathy (CAN) in
      relation to perfusion defects in 146 diabetic patients with suspected coronary
      artery disease. Perfusion defects and CAN were significant univariate predictors
      of death (p=0.05 and p<0.001, respectively) and cardiac events (p<0.001 and
      p<0.002, respectively). However, CAN remained a significant predictor of death
      and cardiac events after adjustment for perfusion defects (both p<0.02), and
      provided prognostic information incremental to that offered by perfusion defects
      alone (p<0.003 and p<0.006, respectively).

PMID- 14675588
TI  - Circulating matrix metalloproteinase-1 and -3 in patients with an acute coronary
      syndrome.
AB  - To elucidate the diagnostic value of serum matrix metalloproteinase (MMP) levels,
      we measured MMP-1 and MMP-3 by a 1-step sandwich enzyme immunoassay. The
      transcardiac gradients of both MMPs were greater in patients with unstable angina
      and acute myocardial infarction than in patients with stable effort angina or
      control patients. Serum MMP levels appear to be a marker of plaque instability in
      patients with acute coronary syndrome.

PMID- 14675589
TI  - Risk factors for premature coronary artery disease and determinants of adverse
      outcomes after revascularization in patients < or =40 years old.
AB  - Smoking is an important and modifiable risk factor associated with premature
      atherosclerosis and the need for coronary revascularization in young adult
      patients < or =40 years old. Although intermediate and long-term survival is
      better in young adult patients after percutaneous coronary intervention, co
      morbidities such as low ejection fraction, previous myocardial infarction, and
      previous bypass surgery are important adverse prognostic determinants.

PMID- 14675590
TI  - Revisiting optimal anticoagulation with unfractionated heparin during coronary
      stent implantation.
AB  - Using univariate and multivariate analyses, we evaluated the relation between
      ischemic and bleeding complications and peak procedural activated clotting time
      (ACT) in patients undergoing percutaneous coronary intervention whose coronary
      narrowings were treated with stent implantation. Of the 2,280 patients who
      qualified for the study, 29% had diabetes mellitus, and 91% received glycoprotein
      IIb/IIIa inhibitors. The median for ACT was 276 seconds (interquartile range 243
      to 317). The incidence of ischemic events by ACT quartiles was 6.3%, 7.5%, 8.1%,
      and 7.1%, respectively (p=0.71). The incidence of bleeding complications was
      6.6%, 5.9%, 6.9%, and 7.3%, respectively (p=0.81). ACT did not independently
      predict either ischemic or hemorrhagic complications.

PMID- 14675591
TI  - Relation between coronary calcium and 10-year risk scores in primary prevention
      patients.
AB  - In 380 patients, coronary calcifications were quantified by electron beam
      tomography and compared with the predicted 10-year cardiovascular event risk
      determined by the Framingham equation, Adult Treatment Panel III tables, and the
      PROCAM algorithm. The correlation between the amount of calcium and the predicted
      cardiac event risk was low (correlation coefficient range 0.19 to 0.28). The
      assessment of coronary calcium may thus potentially yield information that is
      additive to the analysis of traditional risk factors.

PMID- 14675592
TI  - Ethnicity in relation to atrial fibrillation and stroke (the West Birmingham
      Stroke Project).
AB  - To test the hypothesis that ethnic differences may exist in the epidemiology of
      atrial fibrillation (AF) and other cardiovascular conditions among patients
      admitted to the hospital with nonhemorrhagic stroke, we reviewed registry data
      over a 2-year period of 832 consecutive patients admitted with nonhemorrhagic
      stroke to our hospital, which serves a multiethnic population. Indo-Asians and
      Afro-Caribbeans with acute (nonhemorrhagic) stroke had a lower prevalence of AF,
      despite a greater prevalence of diabetes and hypertension, than whites. AF was an
      independent predictor of increased mortality after stroke in our multiethnic
      population as a whole, but AF appears to be a less prominent factor in stroke
      among Indo-Asians and Afro-Caribbeans than in whites.

PMID- 14675593
TI  - Effect of statins on the progression of bioprosthetic aortic valve degeneration.
AB  - To date, there is no proved medical therapy able to significantly reduce the
      degenerative process of biologic prosthetic aortic valves. It has recently been
      suggested that statins may reduce the progression of native aortic valve
      stenosis. We examined the effect of statin treatment on bioprosthetic aortic
      valve degeneration and found a beneficial effect of statins in slowing
      bioprosthetic degeneration.

PMID- 14675594
TI  - Intracardiac echocardiography during transcatheter interventions for congenital
      heart disease.
AB  - Although transesophageal echocardiography is often used for guidance during
      transcatheter interventions, few data exist regarding the use of the newer
      modality of intracardiac echocardiography. This brief report summarizes our
      single center experience using intracardiac echocardiographic guidance during
      transcatheter interventional procedures for congenital heart disease.

PMID- 14675595
TI  - Cause of normal pulmonic velocity in fetal tetralogy of Fallot.
AB  - In 10 fetuses with tetralogy of Fallot, 9 lacked high velocity across the
      obstructed right ventricular outflow tract, which we conclude was due to the
      parallel flow circulations created by the combination of ventricular septal
      defect and arterial duct. The normally high resistance in the fetal pulmonary
      vascular system substantially exceeds the resistance of the systemic vasculature,
      resulting in the maintenance of right-to-left ductal flow in all 10 fetuses who
      had only moderate pulmonary obstruction.

PMID- 14675596
TI  - Effect of angiotensin-converting enzyme insertion/deletion polymorphism DD
      genotype on high-frequency heart rate variability in African Americans.
AB  - Seventy-nine African-American participants in the Healthy Aging in Neighborhoods
      of Diversity across the Life Span (HANDLS) pilot study were genotyped for the
      angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and had
      spectral power of their high-frequency (HF) heart rate variability (HRV)
      determined by fast-Fourier transformation. HF HRV was highest in II, intermediate
      in ID, and lowest in DD (II vs DD, p <0.043) genotypes, thus making an
      association of the ACE I/D DD genotype with decreased HF HRV that is consistent
      with the hypothesis that the DD genotype confers susceptibility to increased
      cardiovascular risk. The urban African-American population we studied had a
      particularly high cardiovascular risk, and these findings suggest that ACE I/D
      genotypes may modify that risk.

PMID- 14675597
TI  - Coronary tracheal collaterals after heart-lung transplant.
AB  - Coronary tracheal collaterals are often seen on annual surveillance coronary
      angiograms in patients with heart-lung transplants and represent a normal
      postoperative finding.

PMID- 14675598
TI  - Incidence of aspirin nonresponsiveness using the Ultegra Rapid Platelet Function
      Assay-ASA.
AB  - We report the incidence of aspirin nonresponsiveness in a prospective,
      multicenter registry (n=422 patients) to be 23% using the Ultegra Rapid Platelet
      Function Assay-ASA, and determined a history of coronary artery disease to be
      associated with twice the odds of being an aspirin nonresponder (odds ratio 2.01,
      95% confidence interval 1.189 to 3.411, p=0.009). Further prospective studies are
      needed to correlate aspirin nonresponsiveness to adverse clinical events.

PMID- 14675601
TI  - Natural course of voiding function in patients with human T-cell lymphotrophic
      virus type 1-associated myelopathy.
AB  - OBJECTIVES: Patients with human T-cell lymphotropic virus type I (HTLV-I)
      associated myelopathy/tropical spastic paraparesis (HAM/TSP) frequently
      experience voiding dysfunction. In patients with HAM/TSP, the major symptoms are
      gait disturbance and voiding dysfunction. However, the detailed natural course of
      voiding function and the management of their urination has not previously been
      investigated. We examined the correlation between voiding function and clinical
      features and evaluated the management of urination, in the patients with HAM/TSP.
      PATIENTS AND METHODS: The voiding function of 47 patients (7 males, 40 females,
      aged 29-89 years, mean: 60.9 years) with HAM/TSP was analyzed retrospectively.
      All HAM/TSP patients are positive for HTLV-1. Patients were referred to a
      neurologist for analysis of bladder function. In the present study, we analyzed
      their clinical details, age at disease onset, voiding function and alterations in
      the management of their urination. Furthermore, we investigated the relationship
      between urological management and the clinical features of HAM/TSP. RESULTS: Of
      the 47 patients, 20 (42.5%) were able to void with or without drug therapy.
      Thirty-four (72.3%) experienced clean intermittent self-catheterization (CIC),
      with 25 of these 34 continuing CIC, 7 changing to voiding and 2 changing to
      management with the Foley catheter. No relationship was noted between disruption
      of voiding function and either age or gender. However, significant inverse
      correlation was observed between the age at disease onset and the time to CIC (r=
      0.77, P=0.00001). CONCLUSIONS: These data suggest that the younger a patients is
      at HAM/TSP onset, the longer voiding function will be maintained.

PMID- 14675602
TI  - Anti-neuronal autoantibody in Hashimoto's encephalopathy: neuropathological,
      immunohistochemical, and biochemical analysis of two patients.
AB  - Hashimoto's encephalopathy (HE) is thought to be caused by disorders of immune
      mechanisms. Although immunologically mediated central nervous system vasculitis
      or unidentified anti-neuronal autoantibodies have been suspected of causing HE,
      its pathogenesis is still unclear. For the study presented here, two patients
      with typical clinical and laboratory/electrophysiological findings of HE were
      analyzed to clarify the role of anti-neuronal autoantibodies in the pathogenesis
      of HE. The autopsied brain of one of the patients was histopathologically
      examined. For Western blotting analysis and immunohistochemistry, serum and
      purified immunoglobulin G obtained from the other patient were used. Autopsy
      revealed no evidence of central nervous system vasculitis or other abnormal
      findings in the brain. The patient's serum contained an anti-neuronal
      autoantibody that immunohistochemically labeled neurons of mouse and human
      cerebral cortices and reacted with the 36-kDa antigenic protein present in a
      soluble fraction obtained from human cerebral cortex. Our results indicate that
      anti-neuronal autoantibodies may be associated with the pathogenesis of HE.

PMID- 14675603
TI  - Association of alpha 2-macroglobulin polymorphisms and Alzheimer disease in
      Mainland Han Chinese.
AB  - This study used case-control method to investigate roles of two alpha 2
      macroglobulin (A2M) polymorphisms, a 5-bp insertion/deletion (A2M-I/D) and an A-
      >G substitution (A2M-A/G), in the development of sporadic Alzheimer disease (AD)
      in Mainland Han Chinese. Our results showed a trend of lower D-carrying genotype
      frequency in APOE-epsilon 4 carrying AD patients than in corresponding control
      subjects (chi(2)=3.67, p=0.055). The ID/AA genotype frequency was lower in AD
      patients comparing with controls (chi(2)=4.04, p=0.044). In AD patients, the G
      carrying genotype frequency was significantly higher in APOE-epsilon 4 carrier
      subgroup than in APOE-epsilon 4 non-carriers (chi(2)=7.38, OR=2.99, 95% CI: 1.33
      6.71, p=0.007). These results indicated that A2M-D allele was probably a weak AD
      protective factor, and there was a possible interaction of APOE-epsilon 4 and A2M
      G alleles to increase AD risk in Mainland Han Chinese.

PMID- 14675604
TI  - Alpha-keto-beta-methylvaleric acid increases the in vitro phosphorylation of
      intermediate filaments in cerebral cortex of young rats through the gabaergic
      system.
AB  - In this study we investigated the effects of alpha-ketoisovaleric (KIV) and alpha
      keto-beta-methylvaleric acids (KMV), metabolites accumulating in the inherited
      neurometabolic disorder maple syrup urine disease (MSUD), on the in vitro
      incorporation of 32P into intermediate filament (IF) proteins from cerebral
      cortex of young rats during development (9-21 days of age) We observed that KMV
      significantly increased the in vitro incorporation of 32P into the IF proteins
      studied in cortical slices of 12-day-old rats through the PKA and PKCaMII, with
      no alteration at the other ages. In contrast, KIV was ineffective in altering the
      phosphorylating system associated with IF proteins at all ages examined. A
      similar effect on IF phosphorylation was achieved by incubating cortical slices
      with gamma-aminobutiric acid (GABA). Furthermore, by using specific GABA
      antagonists, we verified that KMV induced a stimulatory effect on IF
      phosphorylation of tissue slices from 12-day-old rats mediated by GABA(A) and
      GABA(B) receptors. In conclusion, our results indicate the involvement of the
      GABAergic system in the alterations of IF phosphorylation caused by KMV, one of
      the branched-chain keto acids accumulating in MSUD.

PMID- 14675605
TI  - Effects of antineuronal antibodies from patients with paraneoplastic neurological
      syndrome on primary-cultured neurons.
AB  - Some patients with paraneoplastic neurological syndrome (PNS) produce
      autoantibodies against tumor and neuronal tissues of symptom-relevant areas.
      These characteristic antibodies are detected at early stages of the neurological
      disorder and are reliable markers for the diagnosis of PNS and underlying
      cancers. These antibodies are thought to be related directly to neuronal damage.
      However, the passive transfer of antibodies to rodents has been succeeded only in
      those in which the target antigens were expressed on the cell surface, like
      Lambert-Eaton myasthenic syndrome. The serum IgGs from patients with PNS and anti
      Yo or anti-Hu antibody were not shown to induce the disease by passive transfer
      or active immunization with these antigen proteins to date. Instead, cytotoxic T
      lymphocytes (CTLs) against these antigen peptides-presenting targets could be
      induced in the peripheral blood of PNS patients. However, there is no direct
      proof of CTLs killing neurons. In this study, we examined the effects of the anti
      Yo or anti-Hu antibody on mouse-brain-derived neurons in a primary culture system
      and found that these antibodies did not kill neurons, but induced the expression
      of cell adhesion molecules and accelerated neuronal differentiation. These
      effects of serum IgG fractions containing the anti-Yo or the anti-Hu antibody on
      the cultured neurons were the same, suggesting that their effects were not
      through the binding of the antibody to specific antigens, but to some other
      factors contained in IgG fractions.

PMID- 14675606
TI  - Neuron-specific enolase in patients with neurocysticercosis.
AB  - BACKGROUND: Neurocysticercosis (NC) is the most frequent parasitic disease of the
      human nervous system. Its clinical manifestations are varied and depend on the
      number and location of cysts, as well as the host immune response. Symptoms in NC
      usually occur when cysts enter into a degenerative phase associated with
      perilesional inflammation. We speculate that neuron-specific enolase (NSE)--a
      marker of neuronal injury--could be elevated in patients with degenerating cysts
      comparing to those with viable cysts. METHODS: We examined serum NSE (sNSE) and
      cerebrospinal fluid (CSF) NSE (cNSE) levels in 25 patients with NC: 14 patients
      with degenerative cysts (D), 8 patients with viable cysts (V) and 3 patients with
      inactive cysts. Samples of eight normal controls (C) were also obtained.
      Determination of albumin was performed in serum and CSF samples, and the
      CSF/serum albumin ratio (albumin quotient, Q(alb)) was used to estimate the blood
      brain barrier permeability. RESULTS: All patients, with the exception of one
      case, had five or less cysts. Comparisons between V, D and C groups did not
      demonstrate significant differences of cNSE, Q(alb) and sNSE levels. Further,
      there were no significant differences of cNSE and sNSE levels between patients
      with or without intracranial hypertension (ICH). CONCLUSIONS: These findings
      suggest that the inflammatory response associated with a relatively small number
      of degenerating cysts does not provoke significant neuronal damage. Further
      studies considering patients with a larger number of cysts will be required to
      assess if there is evidence of neuronal damage in such more severe cases.

PMID- 14675607
TI  - Successful pregnancies and abortions in symptomatic and asymptomatic Wilson's
      disease.
AB  - BACKGROUND: There are only a few reports regarding the fertility and outcome of
      pregnancy in Wilson's disease (WD) and none from India. The authors in this study
      discuss various aspects of fertility in 16 women with WD. METHODS: Retrospective
      analysis of data from a large cohort of WD, being followed at a tertiary care
      center. RESULTS: Sixteen patients had conceived on 59 occasions with 30
      successful pregnancies, 24 spontaneous abortions, 2 medical terminations of
      pregnancy and 3 still births. Diagnosis of WD was established after conception in
      10 presymptomatic patients while six patients were already on treatment. Among
      these 16 patients, 9 had history of spontaneous abortions and 12 had successful
      pregnancies. None of the clinical features of WD changed during pregnancy, with
      or without treatment. All the 30 babies were full-term and delivered healthy.
      CONCLUSION: Recurrent abortions are common especially in women with untreated
      Wilson's disease. However, successful pregnancies and uneventful full-term
      delivery may occur in mothers of WD on treatment and in undiagnosed, undetected
      presymptomatic patients. Pregnancy does not seem to have adverse effect on the
      clinical course of Wilson's disease. Teratogenecity was not seen in the present
      series with low-dose penicillamine and zinc sulphate.

PMID- 14675608
TI  - Snoring and excessive daytime sleepiness in Parkinson's disease.
AB  - Recent recognition of daytime sleepiness in Parkinson's disease (PD) has prompted
      a search for its causes. Sleepy patients may be more susceptible to sleep attacks
      after the use of dopamine agonists and the recognition of sleep disturbances in
      PD may influence important therapeutic decisions. To identify clinical factors
      influencing excessive daytime sleepiness (EDS) and sleep complaints in PD, we
      studied 86 consecutive patients with clinical diagnosis of PD using a sleep
      questionnaire, the Epworth Sleepiness Scale, the Unified Parkinson's Disease
      Rating Scale and the Montgomery and Asberg Depression Rating Scale. Patients with
      cognitive dysfunction were not included in the study. We found that 49 patients
      (53.3%) had insomnia, 45 (49.9%) restless legs syndrome (RLS), 51 (55.4%) vivid
      dreams, 61 (71.8%) snoring and 29 (31.5%) had EDS. RLS was more frequent in
      patients with longer duration of illness. Snoring was the most important risk
      factor associated with EDS (OR=3.64, 95% CI=1.11-11.9, P=0.03) and a marginal
      association between motor dysfunction and EDS was observed (OR=1.06, 95% CI=1.00
      1.12, P=0.05).

PMID- 14675609
TI  - Expression of peripherin in ubiquinated inclusions of amyotrophic lateral
      sclerosis.
AB  - We evaluated the expression of the type III intermediate filament (IF) protein,
      peripherin (PRP), in ubiquinated inclusions of motor neurons in amyotrophic
      lateral sclerosis (ALS). A previous study showed that overexpression of PRP in
      transgenic mice induces motor neuron disease with formation of PRP-containing
      inclusions before onset of symptoms [J. Cell Biol. 147 (3) (1999) 531]. To
      determine whether PRP inclusions occur in the human disease, we applied
      doublelabeling immunofluorescence to paraffin sections of the spinal cord
      obtained by autopsy of 40 ALS patients with sporadic disease and 39 controls.
      Inclusions that expressed immunoreactive ubiquitin and peripherin were recorded
      by video camera, and the sections were stained by hematoxylin and eosin (H&E) to
      define morphology. Lewy body-like inclusions (LBLIs) were seen in motor neuron
      perikarya of 9 of 40 ALS cases and none in controls; all LBLIs expressed
      peripherin. Skein-like inclusions (SLIs) were identified by ubiquitin, but did
      not express PRP with rare exceptions. Neither skein-like inclusions nor LBLIs
      expressed alpha B-crystallin, neurofilament protein (NF-L, NF-M and NF-H
      subunits), alpha-internexin, actin or alpha-synuclein. Immunoblot of the whole
      spinal cord exhibited a single 57-kDa band of peripherin in ALS patients and
      controls. Our data document the expression of peripherin in LBLIs, which may
      provide a clue to the pathogenesis of neurodegeneration in ALS.

PMID- 14675610
TI  - Ischemic stroke after using over the counter products containing ephedra.
AB  - Dietary supplements containing Ephedra used for weight loss and physical
      performance enhancement such as "herbal ecstasy" are widely available, and it is
      estimated that at least 1% of the adult population have taken these products.
      Ephedra products including Ephedra alkaloids such as phenylpropanolamine or other
      ephedrine compounds are sold under different names such as Metabolife 356, Ripped
      Fuel, Thermadrene, and Shape-Fast Plus. Over 2 years, five patients with ischemic
      infarctions associated with use of Ephedra products were evaluated at Indiana
      University Hospital. Ephedrine, like other sympathomimetic agents, predisposes
      patients to both ischemic and hemorrhagic strokes. People who take over the
      counter Ephedra products that claim to boost weight loss, increase energy, or
      bolster physical performance are at risk of adverse events including ischemic and
      hemorrhagic strokes.

PMID- 14675611
TI  - Trypanosoma cruzi-associated cerebrovascular disease: a case-control study in
      Eastern Colombia.
AB  - Trypanosoma cruzi infection is a common cause of cardiopathy in South America
      leading it eventually to an established stroke; however, the association between
      T. cruzi infection itself and cerebrovascular disease is still unknown. We did a
      case-control study at Eastern Colombia and found that T. cruzi infection was more
      frequent and statistically significant in stroke cases (24.4%) than controls
      (1.9%), (Chi square: 21.72; OR: 16.13; 95% confidence interval (CI): 3.64-71.4;
      p<0.00001). After removing the seropositive patients with cardiological
      abnormalities, the significance still remained by multivariate analysis (p<0.05).
      This is the first case-control study that demonstrated a significant link between
      this infection and symptomatic cerebrovascular disease, mainly ischemic,
      regardless of cardiac abnormalities. Therefore, we recommend that patients with
      stroke must be screened for T. cruzi infection if they currently live or have
      lived in places where this parasite is considered endemic.

PMID- 14675612
TI  - Birth order and neural tube defects: a reappraisal.
AB  - There is evidence that late birth order is associated with some complex
      disorders. For neural tube defects (NTDs) there is no consensus as to whether
      first or increased birth order is associated or not. A meta-analysis of published
      data on NTDs was carried out to ascertain whether there is an increased risk for
      children first born or of high birth order to have NTDs. All data available with
      information regarding the frequency of live births and NTDs cases by birth order
      (1, 2, 3, and 4 or more) were included in the analysis. Effect sizes calculations
      were performed. Children with higher birth order are more likely to have spina
      bifida but not anencephaly. This same effect was also seen for all NTDs combined,
      which probably reflects the association with spina bifida. These results suggest
      the compilation of anencephaly and spina bifida data can be the explanation for
      the controversies seen in the literature.

PMID- 14675613
TI  - Effects of acute repetitive transcranial magnetic stimulation on dopamine release
      in the rat dorsolateral striatum.
AB  - Animal studies have shown that descending pathways from the frontal cortex
      modulate dopamine (DA) release in the striatum. This modulation is thought to be
      relevant to the pathophysiology of Parkinson's disease. In human, repetitive
      transcranial magnetic stimulation (rTMS) can result in functional changes in the
      cortex. The present study intended to clarify the effects of acute rTMS treatment
      using various stimulation intensities on the extracellular DA concentrations in
      the rat dorsolateral striatum. The frontal brain of each rat received acute rTMS
      treatment, which consisted of 500 stimuli from 20 trains in a day. Each train was
      applied at 25 Hz for 1 s with 1-min intervals between trains. The neurochemical
      effects of acute rTMS treatment were investigated by determining the
      extracellular concentrations of DA in the rat dorsolateral striatum using in vivo
      microdialysis. Acute rTMS treatment of the frontal brain using the stimulation
      intensity of almost 110% motor threshold (MT) markedly and continuously increased
      the extracellular DA concentrations in the rat dorsolateral striatum. The present
      study demonstrates that acute rTMS treatment of the frontal brain affects the
      DAergic neuronal system in the rat dorsolateral striatum, and may have
      therapeutic implications for Parkinson's disease.

PMID- 14675614
TI  - Nerve conduction velocity measurements reveal the functional deficit in ceramide
      galactosyl transferase-deficient (cgt-/-) mice.
AB  - Biochemical and ultrastructural studies of ceramide galactosyltransferase (CGT)
      in a CGT-deficient mouse line (cgt-/-) were complemented by nerve conduction
      velocity (NCV) measurements in motor nerves (sciatic nerve in the hind limbs) of
      wild type (wt) and cgt-/- mice. Stimulation and recording electrodes were adapted
      to the small size of developing mice during their myelination period. Motor NCVs
      in wt mice ranged between 16 and 26 m/s but in cgt-/- mice between 6 and 13 m/s,
      which corresponds to the conductance of unmyelinated peripheral nerves. These
      electrophysiologic data provide additional functional parameters to the
      neuropathology of a new form of a dysmyelinosis.

PMID- 14675615
TI  - Clinical gait and balance scale (GABS): validation and utilization.
AB  - Gait and Balance Scale (GABS) consists of historical information and examination
      of 14 different gait and balance parameters designed to assess the severity of
      these functional domains. Thirty-five patients with Parkinson's disease (PD),
      Hoehn and Yahr stages 1-3, were tested during their "off" period. GABS items were
      compared to quantitative data from two computerized gait analysis instruments,
      GAITRite and Pro Balance Master. Intra-class correlation coefficients were
      calculated to establish reliability. Intra-rater test-retest reliability was
      determined using Cohen's Kappa statistic. Concurrent validity was derived using
      the Spearman's rho test with the items from GABS, GAITRite and Balance Master.
      Intra-rater reliability was high with k>0.41 (k=kappa statistic) for 17 items, 6
      had k>0.61. When performing validity measurements, a number of items on the GABS
      had a correlation coefficient significant at p<0.01 (2-tailed). Posture, pull
      test, balance during stance, single limb stance, tandem stance, turning, toe
      walking and functional reach had significant correlation with Balance Master data
      (R=0.46-1). Gait, arm swing, gait speed, steps/5 m, 'up-and-go test', modified
      performance oriented assessment of gait scale and provocative testing had
      significant correlation with the GAITRite items (R=0.51-0.83). GABS is an easy-to
      use comprehensive clinical scale with high intra-rater and internal item
      reliability. We have shown concurrent validity with two computerized gait
      analysis instruments. We expect GABS to have a particular utility in clinical
      trials designed to modify functional impairment associated with abnormalities in
      gait and balance.

PMID- 14675616
TI  - Global aphasia without hemiparesis: lesion analysis and its mechanism in 11
      Korean patients.
AB  - BACKGROUND: Global aphasia without hemiparesis (GAWH) is a rare stroke syndrome.
      This study localized the lesion and examined the pathogenic mechanism in Korean
      patients with GAWH, and investigated whether areas of extensive hypoperfusion
      existed outside the diffusion-weighted imaging (DWI) lesions seen in these
      patients. MATERIAL AND METHODS: Eleven patients were diagnosed with aphasia using
      the Western Aphasia Battery. To identify decreased perfusion, which might be
      functionally relevant to aphasia but not detected by DWI, single photon emission
      tomography (SPECT) was performed in five patients. To uncover the possible
      pathogenic mechanisms of ischemic stroke, vascular and cardiologic work-ups were
      performed in all of the patients. RESULTS: The lesions seen on DWI varied, and
      included both inferior frontal and superior temporal (three), isolated inferior
      frontal (four) or superior temporal (one), subcortical (two), and even parieto
      occipital (one) lesions. Brain SPECT did not reveal an extensive lesion of the
      peri-sylvian area outside the DWI lesion in any of the patients, except one with
      the subcortical lesions. CONCLUSION: Our results indicate that a single lesion in
      different locations may be sufficient to produce GAWH, and the lesion profile and
      stroke mechanism in GAWH are heterogeneous, suggesting that lesions to an area of
      complex functional anatomy result in aphasia.

PMID- 14675617
TI  - Progressive multifocal leukoencephalopathy in an adult patient with ICF syndrome.
AB  - We report on a patient affected by ICF syndrome (immunodeficiency, centromeric
      instability of chromosomes 1, 9 and 16 and facial dysmorphism), who presented
      with slowing in mentation, mild right hemiparesis and focal motor seizures. MRI
      study of the brain suggested a diagnosis of progressive multifocal
      leukoencephalopathy (PML), which was confirmed by JC virus DNA detection on CSF
      by polymerase chain reaction (PCR). This is a unique case of adult infective
      neurological complication described in ICF Syndrome.

PMID- 14675618
TI  - Acyclovir responsive brain stem disease after the Ramsay Hunt syndrome.
AB  - We report an immunocompetent patient with the Ramsay Hunt syndrome (RHS) followed
      days later by brainstem disease. Extensive virological studies proved that
      varicella zoster virus (VZV) was the causative agent. Treatment with intravenous
      acyclovir resulted in prompt resolution of all neurological deficits except
      peripheral facial palsy. This case demonstrates that after geniculate zoster,
      brainstem disease may develop even in an immunocompetent individual and effective
      antiviral therapy can be curative.

PMID- 14675620
TI  - The cytoplasmic tail of Herpes simplex virus glycoprotein H binds to the tegument
      protein VP16 in vitro and in vivo.
AB  - During Herpes simplex virus envelopment, capsids, tegument polypeptides, and
      membrane proteins assemble at the site of budding and a cellular lipid bilayer
      becomes refashioned into a spherical envelope. Though the molecular interactions
      driving these events are poorly understood, several lines of evidence suggest
      that associations between envelope protein cytoplasmic tails and tegument
      polypeptides may play important roles. Consistent with this hypothesis, we show
      here that a fusion of the cytoplasmic tail of gH with Glutathione-S-Transferase
      binds to VP16 in a temperature-dependent manner. VP16 prepared by in vitro
      translation behaves in a similar fashion, demonstrating that the interaction is
      not dependent on other viral polypeptides. Mutational analysis of the gH tail has
      also enabled us to identify amino acid residues critical for VP16 binding in
      vitro. A fusion protein in which the gH tail is fused to the carboxy-terminus of
      GFP coimmunoprecipitates with VP16 in infected cells, indicating that VP16 can
      interact with the gH tail in vivo.

PMID- 14675621
TI  - The E7 oncoprotein of high-risk human papillomavirus type 16 enters the nucleus
      via a nonclassical Ran-dependent pathway.
AB  - E7, the major transforming protein of high-risk human papillomavirus (HPV), type
      16, binds and inactivates the retinoblastoma protein (pRb), and the Rb-related
      proteins p107 and p130. HPV16 E7 is a nuclear protein lacking a classical basic
      nuclear localization signal. In this study we investigated the nuclear import of
      HPV16 E7 oncoprotein in digitonin-permeabilized HeLa cells. HPV16 E7 nuclear
      import was independent of pRb, as an E7(DeltaDLYC) variant defective in pRb
      binding was imported into the nuclei of digitonin-permeabilized cells as
      efficiently as wild-type E7 in the presence of exogenous cytosol. Interestingly,
      we discovered that HPV16 E7 is imported into the nuclei via a novel pathway
      different from those mediated by Kap alpha2beta1 heterodimers, Kap beta1, or Kap
      beta2. Nuclear accumulation of E7 required Ran and was not inhibited by the
      RanG19V-GTP variant, an inhibitor of Kap beta mediated import pathways. Together
      the data suggest that HPV16 E7 translocates through the nuclear pores via a
      nonclassical Ran-dependent pathway, independent of the main cytosolic Kap beta
      import receptors.

PMID- 14675622
TI  - Antiapoptotic regulation by hepatitis C virus core protein through up-regulation
      of inhibitor of caspase-activated DNase.
AB  - The hepatitis C virus (HCV) core protein is considered to influence multiple
      cellular processes. We developed a human hepatoblastoma HepG2-derived inducible
      cell line, Hep191, which allows tightly regulated expression of the core protein
      at relatively low but physiological levels under control of the ecdysone
      regulated promoter. By transcriptional profiling, we identified differentially
      expressed genes, some of which are involved in cell growth or apoptosis such as
      inhibitor of caspase-activated DNase (ICAD), defender against cell death 1, tumor
      necrosis factor (TNF) receptor 1, and cytochrome c oxidase subunit VIII.
      Furthermore, we found that core protein expression increases a steady-state level
      of ICAD protein, possibly through enhancing its promoter activity, and inhibits
      caspase-3 activity induced by anti-Fas antibody. Since Fas- or TNF-mediated DNA
      fragmentation is suppressed in the core-induced Hep191 cells, these findings
      suggest that expression of HCV core at physiological levels confers blocking
      activity of caspase-activated DNase and consequently inhibiting apoptotic cell
      death.

PMID- 14675623
TI  - Baculovirus display of fusion protein of Peste des petits ruminants virus and
      hemagglutination protein of Rinderpest virus and immunogenicity of the displayed
      proteins in mouse model.
AB  - Recombinant Bombyx mori nucleopolyhedroviruses (BmNPV) displaying the
      immunodominant ectodomains of fusion glycoprotein (F) of Peste des petitis
      ruminants virus (PPRV) and the hemagglutinin protein (H) of Rinderpest virus
      (RPV), on the budded virions as well as the surface of the infected host cells
      have been constructed. The F and H protein sequences were inserted in-frame
      within the amino-terminal region of BmNPV envelope glycoprotein GP64 expressing
      under the strong viral polyhedrin (polh) promoter. We improved the recombinant
      virus selection in BmNPV by incorporating the green fluorescent protein gene
      (gfp) as selection marker under a separate promoter within the transfer cassette
      harboring the desired genes. Following infection of the insect larvae or the host
      derived BmN cells with these recombinant BmNPVs, the expressed GP64 fusion
      proteins were displayed on the host cell surface and the budded virions. The
      antigenic epitopes of the recombinant proteins were properly displayed and the
      recombinant virus particles induced immune response in mice against PPRV or RPV.

PMID- 14675624
TI  - The conserved structures of the 5' nontranslated region of Citrus tristeza virus
      are involved in replication and virion assembly.
AB  - The genomic RNA of different isolates of Citrus tristeza virus (CTV) reveals an
      unusual pattern of sequence diversity: the 3' halves are highly conserved
      (homology >90%), while the 5' halves show much more dissimilarity, with the 5'
      nontranslated region (NTR) containing the highest diversity (homology as low as
      42%). Yet, positive-sense sequences of the 5' NTR were predicted to fold into
      nearly identical structures consisting of two stem-loops (SL1 and SL2) separated
      by a short spacer region. The predicted most stable secondary structures of the
      negative-sense sequences were more variable. We introduced mutations into the 5'
      NTR of a CTV replicon to alter the sequence and/or the predicted secondary
      structures with or without additional compensatory changes designed to restore
      predicted secondary structures, and examined their effect on replication in
      transfected protoplasts. The results suggested that the predicted secondary
      structures of the 5' NTR were more important for replication than the primary
      structure. Most mutations that were predicted to disrupt the secondary structures
      fail to replicate, while compensatory mutations were allowed replication to
      resume. The 5' NTR mutations that were tolerated by the CTV replicon were
      examined in the full-length virus for effects on replication and production of
      the multiple subgenomic RNAs. Additionally, the ability of these mutants to
      produce virions was monitored by electron microscopy and by passaging the progeny
      nucleocapsids to another batch of protoplasts. Some of the mutants with
      compensatory sequence alterations predicted to rebuild similar secondary
      structures allowed replication at near wild-type levels but failed to passage,
      suggesting that the 5' NTR contains sequences required for both replication and
      virion assembly.

PMID- 14675625
TI  - Analysis of mutant NS5B proteins encoded by isolates from chimpanzees chronically
      infected following clonal HCV RNA inoculation.
AB  - We hypothesized that mutations in the HCV NS5B polymerase, which occur during
      infection, may affect RNA-dependent RNA polymerase (RdRp) activity. NS5B proteins
      corresponding to a genotype 1a infectious clone and mutants identified in
      chimpanzees following inoculation with the clone were expressed and purified and
      their in vitro RdRp activity was compared to a NS5B genotype 1b control. A Gln-65
      to-His mutation increased RdRp activity by 1.8-fold as compared to the infectious
      clone. Moreover, this NS5B1a protein had RdRp activity similar to the NS5B1b
      control. Three NS5B proteins representing mutations found in another animal had
      no in vitro RdRp activity. All mutations were maintained in the majority
      circulating virus for at least 216 weeks. The results demonstrate that some in
      vivo mutations of NS5B directly enhance in vitro RdRp activity. In addition, they
      suggest that the in vitro RdRp activity of NS5B may not always reflect in vivo
      activity within replication complexes.

PMID- 14675626
TI  - Characterization of a chlorella virus PBCV-1 encoded ribonuclease III.
AB  - Sequence analysis of the 330-kb genome of chlorella virus PBCV-1 revealed an open
      reading frame, A464R, which encodes a protein with 30-35% amino acid identity to
      ribonuclease III (RNase III) from many bacteria. The a464r gene was cloned and
      the protein was expressed in Escherichia coli using the chitin-binding intein
      system. The recombinant PBCV-1 RNase III cleaves model dsRNA substrates, in a
      Mg(2+)-dependent manner, into a defined set of products. The substrate cleavage
      specificity overlaps, but is nonidentical to that of E. coli RNase III. The a464r
      gene is expressed very early during PBCV-1 infection, within 5-10 min p.i. The
      RNase III protein appears at 15 min p.i. and disappears by 120 min p.i. The a464r
      gene is highly conserved among the chlorella viruses. Phylogenetic analyses
      indicate that the PBCV enzyme is most closely related to Mycoplasma pneumoniae
      RNase III.

PMID- 14675627
TI  - The N-terminal domain of APJ, a CNS-based coreceptor for HIV-1, is essential for
      its receptor function and coreceptor activity.
AB  - The human APJ, a G protein-coupled seven-transmembrane receptor, has been found
      to be dramatically expressed in the human central nervous system (CNS) and also
      to serve as a coreceptor for the entry of human immunodeficiency virus type 1
      (HIV-1) and simian immunodeficiency virus (SIV). Studies with animal models
      suggested that APJ and its natural ligand, apelin, play an important role in the
      central control of body fluid homeostasis, and in regulation of blood pressure
      and cardiac contractility. In this study, we characterize the structural and
      functional determinants of the N-terminal domain of APJ in interactions with its
      natural ligand and HIV-1 envelope glycoprotein. We demonstrate that the second 10
      residues of the N-terminal domain of APJ are critical for association with
      apelin, while the first 20 amino acids play an important role in supporting cell
      cell fusion mediated by HIV-1 gp120. With site-directed mutagenesis, we have
      identified that the negatively charged amino acid residues Glu20 and Asp23 are
      involved in receptor and coreceptor functions, but residues Tyr10 and Tyr11
      substantially contribute to coreceptor function for both T-tropic (CXCR4) and
      dual-tropic (CXCR4 and CCR5) HIV-1 isolates. Thus, this study provides
      potentially important information for further characterizing APJ-apelin functions
      in vitro and in vivo and designing small molecules for treatment of HIV-1
      infection in the CNS.

PMID- 14675628
TI  - Flock House virus subgenomic RNA3 is replicated and its replication correlates
      with transactivation of RNA2.
AB  - The nodavirus Flock House virus has a bipartite genome composed of RNAs 1 and 2,
      which encode the catalytic component of the RNA-dependent RNA polymerase (RdRp)
      and the capsid protein precursor, respectively. In addition to catalyzing
      replication of the viral genome, the RdRp also transcribes from RNA1 a subgenomic
      RNA3, which is both required for and suppressed by RNA2 replication. Here, we
      show that in the absence of RNA1 replication, FHV RdRp replicated positive-sense
      RNA3 transcripts fully and copied negative-sense RNA3 transcripts into positive
      strands. The two nonstructural proteins encoded by RNA3 were dispensable for
      replication, but sequences in the 3'-terminal 58 nucleotides were required. RNA3
      variants that failed to replicate also failed to transactivate RNA2. These
      results imply that RNA3 is naturally produced both by transcription from RNA1 and
      by subsequent RNA1-independent replication and that RNA3 replication may be
      necessary for transactivation of RNA2.

PMID- 14675631
TI  - Lipid raft microdomains: key sites for Coxsackievirus A9 infectious cycle.
AB  - Lipid rafts have an important property to preferentially concentrate some
      proteins, while excluding others. Lipid rafts can also act as functional
      platforms for multiple signalling and trafficking processes. Several reports have
      shown that lipid rafts play a crucial role in the assembly of several enveloped
      viruses and possibly their cell entry. In this study we investigated the
      importance of lipid raft formation in Coxsackievirus A9 (CAV-9) entry and cell
      infection. Here by using a variety of biochemical and biophysical methods, we
      report that receptor molecules integrin alphavbeta3 and GRP78, which are
      implicated in CAV-9 infection as well as accessory molecules such as MHC class I,
      are accumulated in increased concentrations in lipid rafts following CAV-9
      infection. In addition our studies revealed that raft integrity is essential for
      this virus since CAV-9 activates the Raf/MAPK signalling pathway within the raft
      and raft-disrupting drugs such as nystatin and MCD can successfully inhibit CAV-9
      infection.

PMID- 14675630
TI  - High levels of SIVmnd-1 replication in chronically infected Mandrillus sphinx.
AB  - Viral loads were investigated in SIVmnd-1 chronically infected mandrills and the
      results were compared with those previously observed in other nonpathogenic
      natural SIV infections. Four naturally and 11 experimentally SIVmnd-1-infected
      mandrills from a semi-free-ranging colony were studied during the chronic phase
      of infection. Four SIVmnd-1-infected wild mandrills were also included for
      comparison. Twelve uninfected mandrills were used as controls. Viral loads in all
      chronically infected mandrills ranged from 10(5) to 9 x 10(5) copies/ml and
      antibody titers ranged from 200 to 14,400 and 200 to 12,800 for anti-V3 and anti
      gp36, respectively. There were no differences between groups of wild and captive
      mandrills. Both parameters were stable during the follow-up, and no clinical
      signs of immune suppression were observed. Chronic SIVmnd-1-infected mandrills
      presented slight increases in CD20+ and CD28+/CD8+ cell counts, and a slight
      decrease in CD4+/CD3+ cell counts. A slight CD4+/CD3+ cell depletion was also
      observed in old uninfected controls. Similar to other nonpathogenic models of
      lentiviral infection, these results show a persistent high level of SIVmnd-1
      replication during chronic infection of mandrills, with minimal effects on T cell
      subpopulations.

PMID- 14675632
TI  - Roles of viral and cellular proteins in the expression of alternatively spliced
      HTLV-1 pX mRNAs.
AB  - The human T cell leukemia virus type 1 (HTLV-1) genome contains a cluster of at
      least five open reading frames (ORFs) near the 3' terminus within the pX region.
      The pX ORFs are encoded by mono- or bicistronic mRNAs that are generated by
      alternative splicing. The various pX mRNAs result from skipping of the internal
      exon (2-exon versus 3-exon isofoms) or from the utilization of alternative splice
      acceptor sites in the terminal exon. The Rex and Tax proteins, encoded by ORFs X
      III and X-IV, have been studied intensively and are encoded by the most abundant
      of the alternative 3-exon mRNAs. The protein products of the other pX ORFs have
      not been detected in HTLV-1-infected cell lines and the levels of the
      corresponding mRNAs have not been accurately established. We have used real-time
      RT-PCR with splice-site specific primers to accurately measure the levels of
      individual pX mRNA species in chronically infected T cell lines. We have asked
      whether virus regulatory proteins or ectopic expression of cellular factors
      influence pX mRNA splicing in cells that were transfected with HTLV-1 provirus
      clones. In chronically infected cell lines, the pX-tax/rex mRNA was present at
      500- to 2500-fold higher levels than the pX-tax-orfII mRNA and at approximately
      1000-fold higher levels than pX-rex-orfI mRNA. Chronically infected cell lines
      that contain numerous defective proviruses expressed 2-exon forms of pX mRNAs at
      significantly higher levels compared to cell lines that contain a single full
      length provirus. Cells transfected with provirus expression plasmids expressed
      similar relative amounts of 3-exon pX mRNAs but lower levels of 2-exon mRNA forms
      compared to cells containing a single, full-length provirus. The pX mRNA
      expression patterns were nearly identical in cells transfected with wild-type,
      Tax-minus, or Rex-minus proviruses. Cotransfection of cells with HTLV-1 provirus
      in combination with SF2/ASF expression plasmid resulted in a relative increase in
      pX-tax/rex mRNA compared to pX-tax-orfII and pX-rex-orfI mRNAs, but did not
      affect exon skipping. Ectopic expression of hnRNP A1 did not affect pX splice
      site utilization, but increased exon skipping, as the level of pX-p21rex mRNA was
      increased by almost 10-fold.

PMID- 14675634
TI  - The human papillomavirus type 11 and 16 E6 proteins modulate the cell-cycle
      regulator and transcription cofactor TRIP-Br1.
AB  - The genital human papillomaviruses (HPVs) are a taxonomic group including HPV
      types that preferentially cause genital and laryngeal warts ("low-risk types"),
      such as HPV-6 and HPV-11, or cancer of the cervix and its precursor lesions
      ("high-risk types"), such as HPV-16. The transforming processes induced by these
      viruses depend on the proteins E5, E6, and E7. Among these oncoproteins, the E6
      protein stands out because it supports a particularly large number of functions
      and interactions with cellular proteins, some of which are specific for the
      carcinogenic HPVs, while others are shared among low- and high-risk HPVs. Here we
      report yeast two-hybrid screens with HPV-6 and -11 E6 proteins that identified
      TRIP-Br1 as a novel cellular target. TRIP-Br1 was recently detected by two
      research groups, which described two separate functions, namely that of a
      transcriptional integrator of the E2F1/DP1/RB cell-cycle regulatory pathway (and
      then named TRIP-Br1), and that of an antagonist of the cyclin-dependent kinase
      suppression of p16INK4a (and then named p34SEI-1). We observed that TRIP-Br1
      interacts with low- and high-risk HPV E6 proteins in yeast, in vitro and in
      mammalian cell cultures. Transcription activation of a complex consisting of
      E2F1, DP1, and TRIP-Br1 was efficiently stimulated by both E6 proteins. TRIP-Br1
      has an LLG E6 interaction motif, which contributed to the binding of E6 proteins.
      Apparently, E6 does not promote degradation of TRIP-Br1. Our observations imply
      that the cell-cycle promoting transcription factor E2F1/DP1 is dually targeted by
      HPV oncoproteins, namely (i) by interference of the E7 protein with repression by
      RB, and (ii) by the transcriptional cofactor function of the E6 protein. Our data
      reveal the natural context of the transcription activator function of E6, which
      has been predicted without knowledge of the E2F1/DP1/TRIP-Br/E6 complex by
      studying chimeric constructs, and add a function to the limited number of
      transforming properties shared by low- and high-risk HPVs.

PMID- 14675633
TI  - Analysis of synergy between divergent simple retrovirus posttranscriptional
      control elements.
AB  - Mason-Pfizer monkey virus (MPMV) and spleen necrosis virus (SNV) are simple
      retroviruses that encode functionally divergent cis-acting RNA elements that use
      cellular proteins to facilitate nuclear export and translation of unspliced viral
      RNA. We tested the hypothesis that a combination of MPMV constitutive transport
      element (CTE) and SNV or MPMV RU5 translational enhancer on unspliced HIV-1 gag
      pol reporter RNA synergistically augments Gag production. Results of transient
      transfection assays validate the hypothesis of synergistic augmentation in COS
      cells, but not 293 cells. RNA targeting experiments verified comparable
      responsiveness to CTE-interactive proteins tethered by RRE and RevM10Tap in COS
      and 293 cells. Exogeneous expression of Tap and NXT1 was necessary and sufficient
      to rescue Gag augmentation in 293 cells. Overexpression experiments established
      that CTE, but not RU5, confers the responsiveness to Tap and NXT1 and that CTE in
      conjunction with Tap and NXT1 conferred a 30-fold increase in translational
      utilization of the cytoplasmic RNA. Our results uncovered a previously
      unidentified role of CTE in conjunction with Tap and NXT1 in commitment to
      efficient cytoplasmic RNA utilization.

PMID- 14675635
TI  - The genomic sequence of ectromelia virus, the causative agent of mousepox.
AB  - Ectromelia virus is the causative agent of mousepox, an acute exanthematous
      disease of mouse colonies in Europe, Japan, China, and the U.S. The Moscow,
      Hampstead, and NIH79 strains are the most thoroughly studied with the Moscow
      strain being the most infectious and virulent for the mouse. In the late 1940s
      mousepox was proposed as a model for the study of the pathogenesis of smallpox
      and generalized vaccinia in humans. Studies in the last five decades from a
      succession of investigators have resulted in a detailed description of the
      virologic and pathologic disease course in genetically susceptible and resistant
      inbred and out-bred mice. We report the DNA sequence of the left-hand end, the
      predicted right-hand terminal repeat, and central regions of the genome of the
      Moscow strain of ectromelia virus (approximately 177,500 bp), which together with
      the previously sequenced right-hand end, yields a genome of 209,771 bp. We
      identified 175 potential genes specifying proteins of between 53 and 1924 amino
      acids, and 29 regions containing sequences related to genes predicted in other
      poxviruses, but unlikely to encode for functional proteins in ectromelia virus.
      The translated protein sequences were compared with the protein database for
      structure/function relationships, and these analyses were used to investigate
      poxvirus evolution and to attempt to explain at the cellular and molecular level
      the well-characterized features of the ectromelia virus natural life cycle.

PMID- 14675636
TI  - The greening of virology: Plant Virology Satellite Symposium, American Society
      for Virology, UC-Davis, July 12, 2003.

PMID- 14675629
TI  - Alterations in HIV-1 LTR promoter activity during AIDS progression.
AB  - HIV-1 variants evolving in AIDS patients frequently show increased replicative
      capacity compared to those present during early asymptomatic infection. It is
      known that late stage HIV-1 variants often show an expanded coreceptor tropism
      and altered Nef function. In the present study we investigated whether enhanced
      HIV-1 LTR promoter activity might also evolve during disease progression. Our
      results demonstrate increased LTR promoter activity after AIDS progression in 3
      of 12 HIV-1-infected individuals studied. Further analysis revealed that multiple
      alterations in the U3 core-enhancer and in the transactivation-response (TAR)
      region seem to be responsible for the enhanced functional activity. Our findings
      show that in a subset of HIV-1-infected individuals enhanced LTR transcription
      contributes to the increased replicative potential of late stage virus isolates
      and might accelerate disease progression.

PMID- 14675637
TI  - Soluble microbial products formation in anaerobic chemostats in the presence of
      toxic compounds.
AB  - Anaerobic chemostats fed on glucose (approximately 10 g chemical oxygen demand
      (COD)/L) were used to investigate the effects of toxicity on soluble microbial
      product (SMP) formation. Addition of the toxic compounds chloroform and chromium
      increased the net accumulation of SMP, despite reducing the percentage of SMP in
      the effluent due to the overwhelming production of volatile fatty acids (VFAs).
      In the reactor spiked with chloroform the normalized accumulation of SMP (SMP/So)
      increased from 2% to 8%, whereas in the reactor spiked with Cr (VI) the SMP/So
      ratio reached as high as 20% after the spike, and in both cases SMP net
      accumulation was proportional to the concentration of toxicant. After the
      chloroform and chromium spikes biomass seemed to produce more extra cellular
      polymeric substances (EPS) suggesting that this might have helped them to cope
      with the stress. Chromatography results indicate that some of the high MW
      compounds present in the SMP might have been due to EPS release into the bulk
      solution, and that other compounds, probably released as a result of cell lysis,
      were also present. Hydrolysis of EPS did not seem to contribute to SMP
      accumulation in the presence of toxic compounds, and DNA analysis suggested that
      cell lysis products was an important contribution to SMP accumulation, in the
      presence of chromium.

PMID- 14675638
TI  - Biosorption of phenol and chlorophenols by acclimated residential biomass under
      bioremediation conditions in a sandy aquifer.
AB  - Phenol and chlorophenols are common environmental contaminants. The fate and
      transport of these chemicals must be sufficiently understood to predict
      detrimental environmental impacts and to develop technically and economically
      appropriate remedial action to minimise environmental degradation. In order to
      gain a better understanding of the many mechanisms influencing the fate of phenol
      and chlorophenols in a sandy aquifer, we conducted biosorption experiments with
      biomass collected from a simulated aquifer polluted by consecutive accidental
      spills of phenol, 2-monochlorophenol, 2,4,6-trichlorophenol and pentachlorophenol
      under continuous bioremediation conditions following a closed-loop configuration
      during 180 days. A comparative study of the biosorption capacity of phenol and
      chlorophenols characterised by different physicochemical properties, at different
      pHs in the range of 6.0+/-0.1 to 9.0+/-0.1 showed the following: (i) the
      biosorption of phenol and chlorophenols on resident biomass was rapid
      (equilibrium reached in less than 2h); (ii) the experimental data followed the
      Freundlich isotherm; (iii) changes in pH from 6.0+/-0.1 to 9.0+/-0.1 resulted in
      a decrease in the equilibrium biosorption capacity (qeq); (iv) both Freundlich
      parameters (KF, n) should be used together as predictive parameters in
      mathematical models to simulate the fate of phenol and chlorophenols in the
      aquifer; (v) qeq of phenol and chlorophenols investigated in this study were
      satisfactorily correlated to their hydrophobicity (Kow) with a correlation factor
      0.98. In addition, available data from other reported studies fell in the same
      correlation curve. The results of the present study should be introduced in
      mathematical models developed to predict the effect of biomass fate and transport
      of contaminants in aquifers during bioremediation conditions.

PMID- 14675639
TI  - Long-term changes in quality of discharge water from abandoned underground coal
      mines in Uniontown Syncline, Fayette County, PA, USA.
AB  - Changes in water quality over 25 years have been documented for discharges from
      an extensive network of abandoned underground coal mines in the Uniontown
      Syncline, Fayette County, PA, USA. A baseline study of 136 mine discharges in the
      syncline was conducted in 1974-1975. In 1998-2000, follow-up water flow and
      quality monitoring was conducted at 21 selected discharges for 2 years to assess
      the degree of mine water-quality improvement since 1974-1975. The data from the
      two periods of time were compared, with consideration of differences in
      measurement methods. The degree and rate of water-quality improvement was found
      to be highly dependent on the amount and duration of flooding in the mine voids.
      Water quality of discharges from the substantially flooded mine voids improved
      significantly, going from acidic water with high sulfate and iron concentrations
      in 1974-1975 to alkaline water with substantially lower sulfate and iron
      concentrations in 1998-2000. In contrast, the water quality in the unflooded
      mines showed less improvement over the 25 years between studies. The water
      discharging from the unflooded mines in 1974-1975 was acidic with high sulfate
      concentrations and in 1998-2000 was still acidic but showed somewhat lower
      sulfate and iron concentrations, reflecting depletion of readily available
      pyrite. The data obtained provide insight into the potential and rate of natural
      amelioration of mine water quality in different abandoned underground coal mine
      systems.

PMID- 14675640
TI  - Toxicity to Daphnia magna and Vibrio fischeri of Kraft bleach plant effluents
      treated by catalytic wet-air oxidation.
AB  - Two Kraft-pulp bleaching effluents from a sequence of treatments which include
      chlorine dioxide and caustic soda were treated by catalytic wet-air oxidation
      (CWAO) at T=463 K in trickle-bed and batch-recycle reactors packed with either
      TiO2 extrudates or Ru(3 wt%)/TiO2 catalyst. Chemical analyses (TOC removal,
      color, HPLC) and bioassays (48-h and 30-min acute toxicity tests using Daphnia
      magna and Vibrio fischeri, respectively) were used to get information about the
      toxicity impact of the starting effluents and of the treated solutions. Under the
      operating conditions, complex organic compounds are mostly oxidized into carbon
      dioxide and water, along with short-chain carboxylic acids. Bioassays were found
      as a complement to chemical analyses for ensuring the toxicological impact on the
      ecosystem. In spite of a large decrease of TOC, the solutions of end products
      were all more toxic to Daphnia magna than the starting effluents by factors
      ranging from 2 to 33. This observation is attributed to the synergistic effects
      of acetic acid and salts present in the solutions. On the other hand, toxicity
      reduction with respect to Vibrio fischeri was achieved: detoxification factors
      greater than unity were measured for end-product solutions treated in the
      presence of the Ru(3 wt%)/TiO2 catalyst, suggesting the absence of cumulative
      effect for this bacteria, or a lower sensitivity to the organic acids and salts.
      Bleach plant effluents treated by the CWAO process over the Ru/TiO2 catalyst were
      completely biodegradable.

PMID- 14675641
TI  - Factors influencing inactivation of Klebsiella pneumoniae by chlorine and
      chloramine.
AB  - Inactivation of Klebsiella pneumoniae cultures by chlorine and chloramine was
      evaluated under different growth conditions by varying nutrient media dilution,
      concentrations of essential inorganic nutrients (FeCl3, MgSO4, phosphate, and
      ammonium salts), and temperature. All inactivation assays were performed at room
      temperature (22-23 degrees C) and near neutral pH (7.2-7.5). C*T(99.9) values for
      chlorine increased >20-fold and for chloramine increased 2.6-fold when cells were
      grown in 100-fold diluted nutrient broth (2NB) solutions (final TOC of 35-40
      mg/L). Background levels of Mg: 6.75 x 10(-2) mM and Fe: 3.58 x 10(-5) mM or high
      levels of FeCl3 (0.01 mM) and MgSO4 (1 mM) during growth resulted in the highest
      resistances to chlorine with C*T(99.9) values of 13.06 (+/-0.91) and 13.78 (+/
      1.97) mg-min/L, respectively. Addition of low levels of FeCl3 (0.001 mM) and
      MgSO4 (0.1 mM) to K. pneumoniae cultures during growth resulted in the lowest
      bacterial resistances to inactivation; C*T(99.9) values ranged from 0.28 (+/
      0.06) to 1.88 (+/-0.53)mg-min/L in these cultures. Increase in growth temperature
      from 22.5 degrees C to 35 degrees C for unamended 2NB cultures resulted in a 42
      fold decrease in C*T(99.9) values for chlorine. A similar change in temperature
      resulted in no significant change in C*T(99.9) values for chloramine. These
      results indicate that inactivation of K. pneumoniae cultures by chlorine was
      highly sensitive to changes in growth conditions unlike inactivation by
      chloramine.

PMID- 14675642
TI  - Radiation-induced degradation of polyvinyl alcohol in aqueous solutions.
AB  - The degradation of polyvinyl alcohol (PVA) by gamma-ray irradiation was
      investigated. Degradation efficiency of PVA was influenced by several factors,
      such as initial PVA concentration, dose rate, pH, and the addition of H2O2. The
      degradation kinetics depended on initial PVA concentration and dose rate. At a
      relatively lower PVA concentration, e.g., 180 mg/L, and a higher dose rate, e.g.,
      55.7 Gy/min, the degradation followed pseudo-first-order kinetics. On the
      contrary, at a higher PVA concentration, e.g., 500 mg/L, but a lower dose rate,
      e.g., 12.1 Gy/min, a pseudo-zero-order reaction occurred. The removal of PVA was
      more effective under acidic or alkaline conditions than that under neutral
      conditions. At a certain dose rate there was an optimal dosage of H2O2 to
      facilitate the degradation of PVA. For instance, at a dose rate of 17.2 Gy/min,
      the optimal H2O2 dosage was found to be about 2.5 mmol/L. Radical scavenging
      experiments, total organic carbon determination, and FTIR analysis on the
      degradation products demonstrated that PVA radiolysis was initiated by *OH and
      H*, leading to chain scission and formation of ketones/enols. Ultimately,
      complete mineralization of PVA was achieved.

PMID- 14675643
TI  - Ultraviolet light inactivation of protozoa in drinking water: a Bayesian meta
      analysis.
AB  - To assess the dose of UV light needed to achieve specified levels of Giardia spp.
      cysts and Cryptosporidium spp. oocysts inactivation in drinking water, a Bayesian
      meta-analysis is used to analyze experimental data from several studies. Of the
      20 studies identified by an extensive data collection effort, 14 (five reported
      experiments on Giardia and nine on Cryptosporidium) were selected for analysis
      based on a set of criteria. A substantial amount of the log inactivation data are
      reported as greater than a given inactivation level (i.e., censored data). The
      Bayesian hierarchical modeling approach used in this study not only properly
      addresses the common concerns in a meta-analysis but also provides a robust
      method for incorporating censored data. Different statistical models will result
      in different estimates of the UV doses needed to achieve a specific inactivation
      level. The Bayesian approach allows us to present the uncertainty in terms of
      risk, which is better suited for supporting US EPA in developing regulations.

PMID- 14675644
TI  - Fenton's oxidation of MTBE with zero-valent iron.
AB  - Methyl tert-butyl ether (MTBE) has become a contaminant of increasing concern in
      the U.S. Traditional remediation technologies are successful in removing MTBE
      from contaminated water, but usually transfer the contaminant from the aqueous to
      another phase. Fenton's oxidation of MTBE provides a promising alternative to
      traditional remediation techniques in that it may mineralize the contaminant
      rather than just phase transfer. This bench-scale study investigated the
      feasibility of Fenton's oxidation of MTBE using zero-valent iron as the source of
      catalytic ferrous iron. The oxidation reactions were able to degrade over 99% of
      the MTBE within 10 min, and showed significant generation, and subsequent
      degradation, of the MTBE oxidation byproduct acetone. Second-order rate constants
      for MTBE degradation were 1.9 x 10(8) M(-1) s(-1) at pH 7.0 and 4.4 x 10(8) M(-1)
      s(-1) at pH 4.0. The total organic carbon was reduced by over 86% when a
      H2O2:MTBE ratio of 220:1 or greater was used.

PMID- 14675645
TI  - Development of a biological filtration model applied for advanced treatment of
      sewage.
AB  - A mathematical model of biological filtration process is developed in this paper.
      A biological filtration process has advantages that filtration action and
      biological activities are combined in a single reactor with aid of filter media.
      Both physical and biological functions are incorporated in this developed model
      to simulate both mechanisms. Backwashing is expressed by the assumption that a
      mean captured solids concentration is input as data, and a captured solids
      concentration is kept at that value during each filtration run. The developed
      model is applied to explain the experimental performance with biological
      filtration reactors, in which batch cultivation of autotrophic bacteria and
      continuous treatment of actual sewage are carried out. Its applicability is
      discussed by comparing the simulated results with the experimental data. This
      model can favourably estimate maximum accumulation of autotrophic bacteria on the
      medium in batch cultivation, long-term treatment performance in continuous
      treatment, details of water quality profiles through the filter bed, and biomass.
      Required hydraulic retention time for nitrification and an appropriate
      recirculation ratio in a winter season are discussed with this model. This model
      predicts that a HRT of 1.1 h or above is required to achieve nitrification with
      remaining NH4(+)-N of less than 1 mgN/L and that an appropriate recirculation
      ratio is 2-3.

PMID- 14675646
TI  - Enhanced ammonia nitrogen removal using consistent biological regeneration and
      ammonium exchange of zeolite in modified SBR process.
AB  - The modified zeo-SBR is recommended for a new nitrogen removal process that has a
      special function of consistent ammonium exchange and bioregeneration of zeolite
      floc. Three sets of sequencing batch reactors, control, zeo-SBR, and modified zeo
      SBR were tested to assess nitrogen removal efficiency. The control reactor
      consisted of anoxic-fill, aeration-mixing, settling, and decanting/idle phases,
      meaning that nitrogen removal efficiency was dependent on the decanting volume in
      a cycle. The zeo-SBR reactor was operated in the same way as the control reactor,
      except for daily addition of powdered zeolite in the SBR reactor. The operating
      order sequences in the zeo-SBR were changed in the modified zeo-SBR. Anoxic-fill
      phase was followed by aeration-mixing phase in the zeo-SBR, while aeration-mixing
      phase was followed by anoxic-fill phase in the modified zeo-SBR to carry NH4(+)-N
      over to the next operational cycle and to reduce total nitrogen concentration in
      the effluent. In the modified zeo-SBR, nitrification and biological regeneration
      occurred during the initial aeration-mixing phase, while denitrification and
      ammonium adsorption occurred in the following anoxic-fill phase. The changed
      operational sequence in the modified zeo-SBR to adapt the ammonium adsorption and
      biological regeneration of the zeolite-floc could enhance nitrogen removal
      efficiency. As a result of the continuous operation, the nitrogen removal
      efficiencies of the control and zeo-SBR were in 68.5-70.9%, based on the 33% of
      decanting volume for a cycle. The zeo-SBR showed a consistent ammonium exchange
      and bio-regeneration in the anoxic-fill and aeration-mixing phases, respectively.
      Meanwhile, the effluent total nitrogen of the modified zeo-SBR showed 50-60 mg
      N/L through ammonium adsorption of the zeolite-floc when the influent ammonium
      concentration was 315 mg N/L, indicating the T-N removal efficiency was enhanced
      over 10% in the same HRT and SRT conditions as those of control and zeo-SBR
      reactors. The ammonium adsorption capacity was found to be 6-7 mg NH4(+)-N/g FSS
      that is equivalent to 40 mg NH4(+)-N/L of ammonium nitrogen removal.

PMID- 14675647
TI  - Field and laboratory arsenic speciation methods and their application to natural
      water analysis.
AB  - The toxic and carcinogenic properties of inorganic and organic arsenic species
      make their determination in natural water vitally important. Determination of
      individual inorganic and organic arsenic species is critical because the
      toxicology, mobility, and adsorptivity vary substantially. Several methods for
      the speciation of arsenic in groundwater, surface-water, and acid mine drainage
      sample matrices using field and laboratory techniques are presented. The methods
      provide quantitative determination of arsenite [As(III)], arsenate [As(V)],
      monomethylarsonate (MMA), dimethylarsinate (DMA), and roxarsone in 2-8 min at
      detection limits of less than 1 microg arsenic per liter (microg As L(-1)). All
      the methods use anion exchange chromatography to separate the arsenic species and
      inductively coupled plasma-mass spectrometry as an arsenic-specific detector.
      Different methods were needed because some sample matrices did not have all
      arsenic species present or were incompatible with particular high-performance
      liquid chromatography (HPLC) mobile phases. The bias and variability of the
      methods were evaluated using total arsenic, As(III), As(V), DMA, and MMA results
      from more than 100 surface-water, groundwater, and acid mine drainage samples,
      and reference materials. Concentrations in test samples were as much as 13,000
      microg As L(-1) for As(III) and 3700 microg As L(-1) for As(V). Methylated
      arsenic species were less than 100 microg As L(-1) and were found only in certain
      surface-water samples, and roxarsone was not detected in any of the water samples
      tested. The distribution of inorganic arsenic species in the test samples ranged
      from 0% to 90% As(III). Laboratory-speciation method variability for As(III),
      As(V), MMA, and DMA in reagent water at 0.5 microg As L(-1) was 8-13% (n=7).
      Field-speciation method variability for As(III) and As(V) at 1 microg As L(-1) in
      reagent water was 3-4% (n=3).

PMID- 14675648
TI  - Effects of organic solutes properties on the volatilization processes from water
      solutions.
AB  - Effects of organic solutes properties, including Henry's law constant (H),
      molecular weight (M), molar volume at normal boiling point (Vb), and solubility
      (S), on the usefulness of rate estimation by reference to a reference substance
      (i.e., reference substance concept) and on the evaporation rate were investigated
      by measuring the volatilization rate constant of organic solutes under different
      environmental conditions, including mixing and surfactants. It was found that if
      benzene was used as a reference substance, the ratio of the solute rate to that
      of benzene (F) becomes insensitive to water mixing, whether the solute possessed
      high or low Henry's law constant. In the presence of surfactants, however, the F
      value changes sharply as the solute solubility decreases. For benzene, toluene,
      ethylbenzene, and xylenes (BTEX), the F values are essentially constant
      irrespective of the presence of other chemicals (including organic compounds,
      surfactants, and salinity) and of the variation in temperature. On the other
      hand, the volatilization rates are closely related to molecular weight
      (solubility) in the existence of mixing (surfactants). Three different
      approaches, i.e., mass-transport theory, modified Knudsen equation, and reaction
      rate concept, were used to evaluate the dependence of solute volatilization rates
      on solute properties. It was concluded that the interaction between solute
      properties and environmental parameters might play a key role in the
      volatilization process of organic solutes under different environmental
      conditions.

PMID- 14675649
TI  - 4-nitrophenol biodegradation in a sequencing batch reactor: kinetic study and
      effect of filling time.
AB  - Biodegradation kinetics of 4-nitrophenol (4NP) was investigated in a lab-scale
      sequencing batch reactor fed with the compound as the sole carbon source. The
      experimental results showed that complete 4NP removal can be easily achieved with
      acclimatized biomass, even if an inhibition kinetics is observed; furthermore, an
      improvement in the removal kinetics is obtained if the substrate concentration
      peak, reached in the reactor at the end of the filling time, is maintained to
      quite a low value. Both long feed phase and high biomass concentration are
      effective in reducing the substrate concentration peak and then improving the
      process efficiency. Kinetic test data are well correlated by the Haldane
      equation, with a saturation constant Ks and an inhibition constant KI, of 17.6
      and 30.7 (mg l(-1) 4NP), respectively, whereas the maximum removal rate was in
      the range of 3.3-8.4 (mg 4NP mg VSS(-1) d(-1)) depending on the substrate
      concentration peak reached in the reaction phase.

PMID- 14675650
TI  - The effect of levitated water on fermentation kinetics.
AB  - The rate of anaerobic glucose fermentation by baker's yeast is found to be
      altered when tap water is replaced with "levitated" (i.e., hydrodynamically
      processed) water. To analyze the effect in more detail, we developed a
      fermentation kinetics model that differentiates between (i) nutrient transport
      into the cell, (ii) the "catabolic" and (iii) the "anabolic" reactions. As a
      result, the levitated water affects specifically the glucose uptake kinetics,
      whereas the other kinetic parameters remain unchanged. Remarkably, the sign of
      the effect changes with the water used to prepare the culture. When levitated
      water is used for both the culture preparation and the fermentation, the rate
      constant of glucose transport is increased by (67+/-25)%, relative to ordinary
      tap-water. When the culture is prepared in ordinary water and only the
      fermentation is performed in levitated water, the rate constant of glucose
      transport decreased by (50+/-12)%. Three-week old levitated water has no
      discernable effect any more.

PMID- 14675651
TI  - Simulation of a mesotrophic reservoir (Lake Pareloup) over a long period (1983
      1998) using ASTER2000 biological model.
AB  - Lake Pareloup is studied since 1983. The model ASTER that simulated the ecosystem
      of the lake during the first phase of the study (1983-1987) has been modified.
      The new model, called ASTER2000 aims to improve the estimation of the trophic
      level and the water quality of different reservoirs. To this purpose, NH4, NO3
      and O2 were added as state variables. Affluents and pumping inflow have also been
      considered in order to consider the evolution of the watershed inflow and the
      variation from year to year in rainfall and pumping inflow. We have a long data
      series (1983-1998) that allows testing the model under different hydro-climatic
      conditions. The model simulates the state variables for this period in a
      satisfactory way. The evolution of nutrient concentrations differences bound to
      year-to-year entries are well represented, which would have been impossible with
      the original model. The addition of variables permits to rely on a larger range
      of the water quality criteria. In combination with the thermal forcing
      (temperature and stratification) provided by the EOLE model, ASTER2000,
      represents a strong and easy tool which could be used on many other reservoirs.
      The main modification necessitated in such applications concerns the type of
      diatoms dominating: consumed or not by the zooplankton. It is also indispensable
      to have input data in line with the structure of the model.

PMID- 14675652
TI  - Hydrodynamic behaviour and comparison of technologies for the removal of excess
      biomass in gas-phase biofilters.
AB  - The hydrodynamic behaviour of a biofilter fed toluene and packed with an inert
      carrier was evaluated on start-up and after long-term operation, using both
      methane and styrene as tracers in Residence Time Distribution experiments.
      Results indicated some deviation from ideal plug flow behaviour after 2-year
      operation. It was also observed that the retention time of VOCs gradually
      increased with time and was significantly longer than the average residence time
      of the bulk gas phase. Non-ideal hydrodynamic behaviour in packed beds may be due
      to excess biomass accumulation and affects both reactor modeling and performance.
      Therefore, several methods were studied for the removal of biomass after long
      term biofilter operation: filling with water and draining, backwashing, and air
      sparging. Several flow rates and temperatures (20-60 degrees C) were applied
      using either water or different chemicals (NaOH, NaOCl, HTAB) in aqueous
      solution. Usually, higher flow rates and higher temperatures allowed the removal
      of more biomass, but the efficiency of biomass removal was highly dependent on
      the pressure drop reached before the treatment. The filling/draining method was
      the least efficient for biomass removal, although the treatment did basically not
      generate any biological inhibition. The efficiency of backwashing and air
      sparging was relatively similar and was more effective when adding chemicals.
      However, treatments with chemicals resulted in a significant decrease of the
      biofilter's performance immediately after applying the treatment, needing periods
      of several days to recover the original performance. The effect of manually
      mixing the packing material was also evaluated in duplicate experiments. Quite
      large amounts of biomass were removed but disruption of the filter bed was
      observed. Batch assays were performed simultaneously in order to support and
      quantify the observed inhibitory effects of the different chemicals and
      temperatures used during the treatments.

PMID- 14675653
TI  - Advanced oxidation of the pharmaceutical drug diclofenac with UV/H2O2 and ozone.
AB  - Diclofenac, a widely used anti-inflammatory drug, has been found in many Sewage
      Treatment Plant effluents, rivers and lake waters, and has been reported to
      exhibit adverse effects on fish. Advanced oxidation processes, ozonation and
      H2O2/UV were investigated for its degradation in water. The kinetic of the
      degradation reaction and the nature of the intermediate products were still
      poorly defined. Under the conditions adopted in the present study, both ozonation
      and H2O2/UV systems proved to be effective in inducing diclofenac degradation,
      ensuring a complete conversion of the chlorine into chloride ions and degrees of
      mineralization of 32% for ozonation and 39% for H2O2/UV after a 90 min treatment.
      The reactions were found to follow similar, but not identical, reaction pathways
      leading to hydroxylated intermediates (e.g. 2-[(2,6-dichlorophenyl)amino]-5
      hydroxyphenylacetic acid) and C-N cleavage products (notably 2,5
      dihydroxyphenylacetic acid) through competitive routes. Subsequent oxidative ring
      cleavage leads to carboxylic acid fragments via classic degradation pathways. In
      the pH range 5.0-6.0 kinetic constants (1.76 x 10(4)-1.84 x 10(4) M(-1) s(-1))
      were estimated for diclofenac ozonation.

PMID- 14675654
TI  - Assessing wastewater metal toxicity with bacterial bioluminescence in a bench
      scale wastewater treatment system.
AB  - The effectiveness of a previously developed toxicity monitoring method for
      activated sludge wastewater treatment employing a bioluminescent bacterium (Shk1)
      was evaluated in batch experiments and a bench-scale activated sludge system
      exposed to heavy metals (Cu, Zn, Ni, and Cd). Influent wastewater (primary
      clarifier supernatant) and activated sludge from a municipal wastewater treatment
      plant were used in both batch experiments and in the bench-scale wastewater
      treatment system. Shk1 bioluminescence was most sensitive to Cd and Zn, followed
      by Cu, and then Ni in order of decreasing sensitivity. In contrast, activated
      sludge specific oxygen uptake rate was most sensitive to Cu, followed by Cd and
      Zn, and finally Ni. The same pattern of sensitivity was observed in batch and
      bench-scale evaluations. Batch experiments examining the effect of metal
      adsorption were performed. The adsorption of metals to activated sludge and
      reduction in bioavailability due to chelation by soluble organics or by
      precipitation in wastewater was found to be an important effect in mediating
      differences in toxicity response between bioluminescence and respirometry. Batch
      adsorption experiments indicated that the activated sludge adsorption capacity
      was highest for Cu, followed by Cd, Ni, and then Zn. A simple mathematical model
      for the soluble metal concentration in the aeration basin and clarifier was
      developed utilizing metal distribution coefficients determined from the batch
      adsorption experiments. Model predictions compared well with results from the
      bench-scale activated sludge experiments.

PMID- 14675655
TI  - Factors influencing flux decline during nanofiltration of solutions containing
      dyes and salts.
AB  - In this paper, factors influencing the flux decline of nanofiltration membranes
      for the treatment of dye bath wastewaters were investigated. Experiments were
      performed with synthetic wastewaters. Synthetic solutions were prepared in
      different dye and salt concentrations at laboratory conditions. Operating
      conditions including cross-flow velocity and pH were changed to observe the
      effects of interactions between NaCl, dyes and the membrane. Cake formation rate
      of dye molecules on membrane surface with time was investigated by using
      linearized forms of cake filtration equations. The results suggest that cake
      layer formation of dye molecules on membrane surface, especially at low salt
      concentrations was the principal cause of flux decline. Operating conditions had
      a strong influence on permeate flux. Effects of cross-flow velocity on permeate
      flux were more pronounced at low NaCl concentrations. Furthermore, the lowest
      permeate flux values were obtained at the alkaline conditions due to increased
      dye hydrophobicity at high pH values.

PMID- 14675656
TI  - Bacterial population changes in hospital effluent treatment plant in central
      India.
AB  - Hospital effluent with its high content of multidrug resistant (MDR)
      enterobacteria and the presence of enteric pathogens could pose a grave problem
      for the community. It was planned at our tertiary care hospital in central India
      to study the population changes at various steps of effluent treatment plant
      (ETP) like collection, aeration, clarification, liquid sludge, dried sludge, high
      pressure filter and treated wastewater. The study included viable bacterial
      counts, coliform counts, staphylococcal, enterococcal, Pseudomonas and multiple
      drug resistant (MDR) gram negative bacterial counts in the different stages of
      ETP. In order to study the distribution of bacteria as free floating in liquid
      and adherent to suspended particles, enumeration of the bacteria in the filterate
      and the sediment was also carried out. The effluent input showed 55% of the 8.6 x
      10(6)/ml bacteria as coliforms and E. coli which was a typical of fecal flora.
      The prevalence of MDR coliforms was 0.26%. The substantial reduction (> 3log) was
      seen for the effluent coming from the clarifier. The bulk of the bacteria in the
      hospital effluent remains firmly adhered to solid particles; aeration and
      clarification removes bulk of the bacteria by physical processes like
      flocculation. The treated liquid effluent still contains sizeable loads of MDR
      bacteria and inactivation by procedure such as chlorination is required. The
      bacteria get concentrated in sludge and a greater concentration of chlorine is
      required for decontamination.

PMID- 14675657
TI  - Removal of dissolved rhenium by sorption onto organic polymers: study of rhenium
      as an analogue of radioactive technetium.
AB  - Technetium (99Tc) is one of the main components of nuclear wastes. Tc
      characteristics can be predicted by studying rhenium (75Re), one of its chemical
      analogue, thus avoiding the use of a radioactive element at high concentrations.
      The objectives of this experimental study was to understand the sorption behavior
      of Re with natural organic materials in order to define the possible condition of
      Tc uptake in case where Tc may be transferred into surface or ground waters. As
      the well-defined organic sorbents we chose chitosan which contains amine -NH2
      groups; poly-galacturonic acid (PGA) and poly-styrene sulfonates (PSS) which
      contain respectively carboxyl -COOH and sulfonate -SO3H groups. Concerning the
      reaction of Re with PGA or with PSS, no interaction between Re and carboxyl or
      sulfonate groups was found within the detection limit of this study. Re sorption
      on chitosan was found to be dependent on ionic strength and pH. We propose that
      non-specific sorption of perrhenate ion ReO4- via electrostatic interaction takes
      place at the protonated amine groups NH3+. The polymer-solution interface can be
      described by the electric diffuse double layer model combined with the Langmuir
      Freundlich model. The calculation is in good agreement with our experimental
      results.

PMID- 14675658
TI  - Pre-coagulation for microfiltration of an upland surface water.
AB  - The effect of different coagulants on cake formation and hydraulic resistance in
      membrane filtration of strongly coloured (SUVA> or =4.8) upland surface water has
      been studied at bench-scale under constant pressure conditions. Coagulants used
      were aluminium sulphate, polyaluminium chloride, ferric chloride and ferric
      sulphate. Optimisation of coagulation parameters was carried by conventional jar
      testing. The R'c (specific cake resistance in m(-2)) values were determined for
      all coagulants over a range of coagulant doses and slow mixing flocculation
      periods. Experiments indicated slight differences in cake formation trends
      between ferric- and aluminium-based coagulants and chloride and sulphate
      counterions, but that the range of measured R'c values was small (0.9 and 2.6 x
      10(18) m(-2)) over the range of doses studied. Greater than 99% UV(254) removal
      was achieved with every coagulant, whereas dissolved organic carbon (DOC) removal
      ranged from 78% to 88%. Optimisation of the pre-coagulation-membrane filtration
      process suggests ferric chloride to be slightly superior for the feedwater matrix
      studied on the basis of DOC removal, whereas ferric sulphate gave slightly lower
      filter cake specific resistance values.

PMID- 14675659
TI  - Microalgae growth-promoting bacteria as "helpers" for microalgae: a novel
      approach for removing ammonium and phosphorus from municipal wastewater.
AB  - A combination of microalgae (Chlorella vulgaris or C. sorokiniana) and a
      microalgae growth-promoting bacterium (MGPB, Azospirillum brasilense strain Cd),
      co-immobilized in small alginate beads, was developed to remove nutrients (P and
      N) from municipal wastewater. This paper describes the most recent technical
      details necessary for successful co-immobilization of the two microorganisms, and
      the usefulness of the approach in cleaning the municipal wastewater of the city
      of La Paz, Mexico. A. brasilense Cd significantly enhanced the growth of both
      Chlorella species when the co-immobilized microorganisms were grown in
      wastewater. A. brasilense is incapable of significant removal of nutrients from
      the wastewater, whereas both microalgae can. Co-immobilization of the two
      microorganisms was superior to removal by the microalgae alone, reaching removal
      of up to 100% ammonium, 15% nitrate, and 36% phosphorus within 6 days (varied
      with the source of the wastewater), compared to 75% ammonium, 6% nitrate, and 19%
      phosphorus by the microalgae alone. This study shows the potential of co
      immobilization of microorganisms in small beads to serve as a treatment for
      wastewater in tropical areas.

PMID- 14675660
TI  - A comparative study of Cyperus papyrus and Miscanthidium violaceum-based
      constructed wetlands for wastewater treatment in a tropical climate.
AB  - The treatment efficiencies of constructed wetlands containing Cyperus papyrus L.
      (papyrus) and Miscanthidium violaceum (K. Schum.) Robyns (synonymous with
      Miscanthus violaceum (K. Schum) Pilg.) were investigated in a tropical climate
      (Kampala, Uganda). Papyrus showed higher ammonium-nitrogen and total reactive
      phosphorus (TRP) removal (75.3% and 83.2%) than Miscanthidium (61.5% and 48.4%)
      and unplanted controls (27.9% ammonium-nitrogen). No TRP removal was detected in
      control effluent. Nutrients (N and P) were significantly higher (p<0.015) in
      papyrus than Miscanthidium plant tissues. Plant uptake and storage was the major
      factor responsible for N and P removal in treatment line 2 (papyrus) where it
      contributed 69.5% N and 88.8% P of the total N and P removed. It however
      accounted for only 15.8% N and 30.7% P of the total N and P removed by treatment
      line 3 (Miscanthidium violaceum). In addition, papyrus exhibited a significantly
      larger (p=0.000) number of adventitious roots than Miscanthidium. Nitrifying
      bacteria attached to papyrus (2.15 x 10(6)+/-1.53 x 10(5) MPN/g DW) and
      Miscanthidium roots (1.30 x 10(4)+/-8.83 x 10(2) MPN/g DW) and the corresponding
      nitrification activities were consistent with this finding. Epiphytic nitrifiers
      appeared more important for total nitrification than those in peat or suspended
      in water. Papyrus root structures provided more microbial attachment sites,
      sufficient wastewater residence time, trapping and settlement of suspended
      particles, surface area for pollutant adsorption, uptake, assimilation in plant
      tissues and oxygen for organic and inorganic matter oxidation in the rhizosphere,
      accounting for its high treatment efficiency.

PMID- 14675661
TI  - Floc morphology and cyclic shearing recovery: comparison of alum and polyaluminum
      chloride coagulants.
AB  - This study investigated the floc formation and re-aggregation potential for alum,
      polyaluminum chloride (PACl) and a blend of these coagulants. Bench-scale testing
      included floc morphology characterization for well-developed floc, post-shear
      floc, and non-settleable (filter influent) floc. Different applications of
      coagulants were observed to produce non-settleable floc that was morphologically
      different. The alum treatment had a decrease in average floc size from coagulated
      to non-settleable conditions, whereas the PACl and PACl/alum treatments resulted
      in similar sized floc between these processes. Zeta potential distribution
      measurements showed that the alum treatment resulted in a negative shift from
      coagulated to non-settleable conditions whereas the PACl and PACl/alum treatments
      had no significant shift. A photometric dispersion analyzer (PDA) was employed to
      compare the differences between coagulant treatments with respect to shear
      induced aggregate breakup and recovery. The PDA allowed a dynamic monitoring of
      initial floc aggregation and measured the degree of recovery from cyclic
      shearing. The degree of recovery from shearing was greatest for the PACl/alum
      treatment likely as a result of increased collision efficiency due to more
      effective charge neutralization.

PMID- 14675662
TI  - Uterine papillary serous carcinomas: the exigency for clinical trials.

PMID- 14675663
TI  - Uterine papillary serous carcinoma (UPSC): a single institution review of 129
      cases.
AB  - OBJECTIVE: The aim of this study was to identify clinical and pathologic
      characteristics of patients with uterine papillary serous carcinoma (UPSC) who
      were all surgically managed at a single institution. The identified
      characteristics were then correlated with overall survival (OS). METHODS: One
      hundred twenty-nine patients with FIGO stage I-IV UPSC who were surgically staged
      at the University of Texas M. D. Anderson Cancer Center between 1989 and 2002
      were identified. For each patient, medical records and pathology reports were
      reviewed. The Kaplan-Meier method was used to generate OS data. Factors
      predictive of outcome were compared using the log-rank test and Cox regression
      analysis. RESULTS: There were 52 patients with stage I disease, 5 with stage II,
      41 with stage III, and 31 with stage IV. The median age at the time of diagnosis
      was 68 years (range, 44-93 years). A personal history of breast cancer was
      reported by 12.4% of the patients, and a family history of breast cancer was
      reported by 16%. The 5-year OS among all patients was 45.9%. Among the stage I
      patients (IA, n = 19; IB, n = 26; and IC, n = 7), the 5-year OS was 62.9% (IA,
      81.5%; IB, 58.6%; and IC, 34.3%). The 5-year OS for patients with stage III and
      IV disease was 37.3 and 19.9%, respectively. Pathologic features predictive of OS
      included lymph node status (P </= 0.01), lymph vascular invasion (P </= 0.05),
      and depth of uterine invasion (P </= 0.05). Among patients with no uterine
      invasion (n = 32), surgical staging revealed that 37% had stage III or IV
      disease. Among stage III patients, those who received chemotherapy had a longer
      OS than those who did not receive chemotherapy (P = 0.03). CONCLUSION: In this
      population of nonselected patients with UPSC, approximately 20% had a personal or
      family history of breast cancer. Stage, lymph node status, lymph vascular
      invasion, and depth of myometrial invasion were all risk factors for a worse
      prognosis. Traditional risk factors, however, did not predict the presence or the
      absence of metastasis. Among patients with noninvasive uterine disease, there was
      a high proportion with abdominal metastasis. Therefore, complete surgical staging
      of these patients is vital in determining their prognosis.

PMID- 14675664
TI  - Uterine papillary serous carcinoma: comparisons of outcomes in surgical Stage I
      patients with and without adjuvant therapy.
AB  - OBJECTIVE: Our aim was to determine the outcomes of Stage I uterine papillary
      serous carcinoma (UPSC) patients with and without adjuvant therapy after
      comprehensive surgical staging. METHODS: Patients with FIGO Stage I UPSC
      diagnosed from 1987 to 2000 were identified from tumor registry databases at four
      institutions. A retrospective chart review identified 60 women who underwent
      comprehensive surgical staging, including a total hysterectomy, bilateral
      salpingo-oophorectomy, pelvic/para-aortic lymphadenectomy, and peritoneal
      cytology. Fisher's exact, chi(2), and log-rank tests were used for the
      statistical analyses. RESULTS: Of the 60 Stage I patients, 40 (66%) patients
      received no adjuvant therapy, 12 (20%) received adjuvant radiation therapy (XRT),
      7 (12%) received adjuvant chemotherapy (CHM), and 1 (2%) received both XRT and
      CHM. There were seven recurrences in the observation group versus two recurrences
      in the XRT group (17% vs 16%, P = 0.9). No recurrences or deaths were observed in
      the CHM group. The mean disease-free survival rates for the observation and the
      XRT groups were 31 and 41 months, respectively. The mean overall survival rates
      for the observation and XRT groups were 39 and 40 months, respectively. The 5
      year disease-free survival rates for the observation and XRT groups were 65 and
      60%, respectively; the 5-year overall survival rates for observation and XRT
      groups were 66 and 59%. There was no statistical difference in overall survival
      among the three groups. CONCLUSION: In this largest reported series of surgical
      Stage I UPSC patients, recurrence rates were lower than those published in
      previous studies, suggesting a potential benefit of comprehensive surgical
      staging in these patients. The risk of recurrence and the mean overall survival
      were similar between surgical Stage I UPSC patients who were managed
      conservatively and those treated with adjuvant radiation therapy. These data
      question the benefit of radiation therapy in UPSC patients with disease confined
      to the uterus. Finally, given the absence of recurrences and disease-related
      deaths for adjuvant chemotherapy in these patients, a Phase II/III trial
      evaluating adjuvant chemotherapy in surgical Stage I UPSC patients should be
      considered.

PMID- 14675665
TI  - Relationship between HPV typing and abnormality of G1 cell cycle regulators in
      cervical neoplasm.
AB  - OBJECTIVE: In tumorigenesis, loss of function of the G1 pathway (p16
      CDK4/cyclinD1-pRB pathway (RB pathway) and p14-MDM2-p53 pathway (p53 pathway)) is
      a theoretically essential event. The simultaneous analysis of all components of
      the RB and p53 pathway may be able to explain cervical tumorigenesis. However,
      there are no reports in which all components of the G1 pathway and HPV typing
      were examined simultaneously in cervical cancer. METHODS: We examined HPV typing
      and the status of the G1 pathways simultaneously by PCR-SSCP, multiplex PCR,
      methylation-specific PCR, and immunohistochemical techniques in cervical
      neoplasia. A total of 105 samples (normal, 10; cervical intraepithelial neoplasm
      (CIN), 42; invasive cancer (IC), 53) were included. RESULTS: Abnormality of the
      RB pathway tended to be more frequent in ICs (60.4%) than in CINs (31.0%) (P =
      0.069). The primary target was p16 (CIN, 14.3%; IC, 43.4%; P = 0.032).
      Abnormality of the p53 pathway was detected in ICs (56.6%) and in CINs (40.5%) (P
      = 0.1494). In particular, strong expression of MDM2 was higher in ICs (32.1%)
      than in CINs (7.1%) (P = 0.0045). Abnormalities of the RB and p53 pathways were
      higher in low-risk and negative HPV than in high-risk HPV (81.3% vs 51.4%, P =
      0.0657; 81.3% vs 45.9%, P = 0.0328). Seven HPV-negative cases had abnormalities
      in the RB or p53 pathways. CONCLUSION: In conclusion, abnormality of the G1
      pathway may be one of the important mechanisms for carcinogenesis of low-risk and
      negative HPV cases.

PMID- 14675666
TI  - Circulating levels of insulin-like growth factor-II and IGF-binding protein 3 in
      cervical cancer.
AB  - OBJECTIVE: We aimed to further document that elevated levels of circulating
      insulin-like growth factor II (IGF-II) are associated with cervical cancer and to
      test the hypothesis that there may be an inverse association between IGF-II and
      IGF-binding protein 3 (IGF-BP3). METHODS: Serum IGF-II and IGF-BP3 levels were
      measured, using ELISA kits (Diagnostic Systems Laboratories), in 23 controls; 16
      ASC-US with normal biopsies; 14 ASC-US with advanced CIN; 2 pretherapy CIN-I; 8
      successfully treated CIN-I; 24 persistent CIN I; 14 pretherapy CIN II/III; 10
      posttherapy CIN II/III with normal biopsies; 18 persistent CIN-II/III; 7 with
      pretherapy cervical cancer; 19 with posttherapy cervical cancer under remission;
      15 with posttherapy persistent/recurrent cervical cancer; 10 with persistent
      ovarian or endometrial cancer; and 3 with endometrial or vulvar with cervical
      cancer. Student's t test and linear regression analysis were used. RESULTS:
      Compared to controls (493 +/- 90 ng/ml) and women with other gynecological
      cancers, serum IGF-II levels were significantly increased in women with ASC-US,
      with advanced CIN on biopsy (P < 0.0001), persistent CIN-I (993 +/- 262 ng/ml; P
      < 0.0001), pretherapy advanced CIN (1086 +/- 240; P < 0.0001), pretherapy
      cervical cancer patients (1746 +/- 318 ng/ml; P < 0.0001) and posttherapy
      persistent/recurrent CIN (1094 +/- 300; P < 0.0001); and cervical cancer (1395 +/
      189; P < 0.0001). After therapy, the IGF-II levels returned to normal in both
      CIN and cervical cancer patients under remission. Elevated serum IGF-II levels
      had 100% sensitivity and 87% specificity for cervical cancer and 81% sensitivity
      and 82% specificity for CIN. The levels of IGF-BP3 were significantly reduced in
      women with CIN before and after therapy (P < 0.0001) and in cervical cancer
      patients before and after therapy (P < 0.001). There was an inverse relationship
      between serum IGF-II and BP-3 levels (P < 0.01). Decreased serum IGF-BP3 levels
      had a sensitivity of 72% and specificity of 75% for cervical cancer and 81%
      sensitivity and 83% specificity for CIN. When both markers were considered
      together the sensitivity was 72% and specificity 84% for cervical cancer, while
      for CIN, the sensitivity was 57% and specificity 81%. CONCLUSION: Serum IGF-II
      may be a reliable marker for early diagnosis and monitoring therapy efficacy
      (sensitivity and specificity of 100% versus normal controls), while IGF-BP3
      levels can be reliably used to predict prognosis.

PMID- 14675667
TI  - Laparoscopic sentinel node mapping in early-stage cervical cancer.
AB  - OBJECTIVE: We aimed to determine the feasibility and accuracy of sentinel node
      (SN) mapping and its ability to predict the status of the regional nodal basin.
      METHODS: From October 2000 to September 2002, 70 patients undergoing radical
      surgery for early-stage cervical cancer (stage IA, IB, and IIA) were offered
      lymph node mapping for identification of the sentinel node. All patients
      underwent SN identification laparoscopically followed by a complete laparoscopic
      pelvic node and parametrial dissection. The SN mapping was done after
      intracervical blue dye injection in all cases and was combined with preoperative
      lymphoscintigraphy following intracervical Tc-99 injection and intraoperative SN
      detection with a miniaturized laparoscopic gamma probe in 29 cases (42%).
      RESULTS: The blue dye technique alone (n = 70) identified at least 1 SN in 61
      (87%) of the patients. The rate of SN detection by side of dissection was 74%,
      70% on the left side and 77% on the right side. Bilateral SN were identified in
      60% of cases. In the subgroup of patients who had the combined technique (n =
      29), the rate of SN detection increased from 79 to 93% (P = 0.04). The bilateral
      SN detection rate increased from 55 to 72% when adding lymphoscintigraphy (P =
      0.03). In the last 15 cases of the series, the SN detection rate reached 93%
      (14/15) and this was statistically significant compared to the detection rate of
      the first 55 cases (P < 0.01). A total of 135 SN were identified, with the
      majority (88%) being located at three main sites: the external iliac, obturator,
      and bifurcation. Thirty-six patients (51%) had 2 SN identified, and 16 (24%) had
      3 SN or more. Twelve (17%) patients had positive lymph nodes. In those cases, the
      rate of SN detection per side of dissection in patients with normal appearing
      nodes at laparoscopy was 75%, whereas it was only 56% in patients with
      macroscopically involved lymph nodes (P = NS). The false negative rate was 0. The
      negative predictive value of SN mapping was 100% and the sensitivity was 93% with
      the combined technique. Two patients had allergic reactions to the blue dye (3%).
      CONCLUSION: Sentinel node mapping with the combined blue dye technique and
      lymphoscintigraphy in patients with cervical cancer is laparoscopically feasible
      and is highly accurate. The detection rate improves significantly with experience
      and with the use of lymphoscintigraphy.

PMID- 14675668
TI  - Distinct subtypes of serous ovarian carcinoma identified by p53 determination.
AB  - OBJECTIVE: The overall prognosis of ovarian carcinoma is poor. However, the
      outcome of apparently similar cases is highly variable, and molecular markers
      that would predict disease outcome in a clinically useful manner are lacking. We
      investigated the value of p53 expression as a disease determinant in serous
      carcinoma, which is the most common type of ovarian carcinoma and has shown the
      highest frequency of p53 alterations. METHODS: Tissue microarray constructed of
      522 serous ovarian carcinomas was examined immunohistochemically using DO-7
      monoclonal antibody against p53 protein. The findings were correlated with
      overall and disease-free survival, response to therapy, and clinicopathological
      characteristics of the patients. RESULTS: Both excessive and completely negative
      p53 staining confered poor patient outcome and were considered aberrant p53
      expression. Patients with aberrant p53 (59% of the carcinomas) showed 5-year
      overall survival of 26% (20-31%), whereas patients with normal p53 expression
      (41% of the carcinomas) showed 5-year overall survival of 79% (95% CI, 74-85%) (P
      < 0.0001). The association of aberrant p53 with poor prognosis was independent of
      clinicopathological parameters, e.g., stage and grade. In addition, aberrant p53
      status was significantly associated with shorter disease-free survival (P <
      0.0001) and poor response to therapy (P < 0.0001). In the most common subgroups,
      stage III and stage I carcinomas, 5-year overall survival rates for patients
      showing normal p53 vs. aberrant p53 were 72% vs. 19% (P < 0.0001) and 99% vs. 56%
      (P < 0.0001), respectively. CONCLUSION: P53 expression status divides serous
      ovarian carcinomas into two distinct subtypes: one with a relatively good
      prognosis and the other with a particularly poor outcome.

PMID- 14675669
TI  - VEGF and HIF-1alpha expression are increased in advanced stages of epithelial
      ovarian cancer.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) is a potent angiogenic
      factor that is elevated in epithelial ovarian cancer. Hypoxia inducible factor
      1alpha (HIF-1alpha) is a transcription factor that plays a regulatory role in the
      expression of VEGF. Currently, there is limited information regarding VEGF and
      HIF-1alpha expression in epithelial ovarian cancer specimens. The objective of
      this study was to measure VEGF and HIF-1alpha expression in epithelial ovarian
      cancer samples and to compare VEGF and HIF-1alpha expression between ovarian
      cancer and normal ovarian tissue METHODS: . Serial sections of paraffin-embedded
      ovarian tissues from a study group of 16 control patients and 37 patients
      diagnosed with epithelial ovarian cancer were analyzed for expression of VEGF and
      HIF-1alpha using immunohistochemistry. RESULTS: There was a strong correlation
      between the average expression scores of VEGF and HIF-1alpha expression (r(2) =
      0.991). There was a significant increase in expression of VEGF in stage III and
      IV tumors over that in controls (P < 0.005). There was also a significant
      increase in HIF-1alpha expression in stage III and IV tumors over that in
      controls (P < 0.005 and P < 0.05, respectively). CONCLUSION: VEGF and HIF-1alpha
      are both expressed in epithelial ovarian cancer. VEGF expression correlated with
      HIF-1alpha expression, suggesting that HIF-1alpha may contribute to the
      overexpression of VEGF observed in epithelial ovarian cancer.

PMID- 14675670
TI  - Cytokeratin staining of resected lymph nodes may improve the sensitivity of
      surgical staging for endometrial cancer.
AB  - OBJECTIVE: The presence of metastases to regional lymph nodes (LN) is the single
      most important risk factor in endometrial cancer. Advances in molecular biology
      have provided more sensitive methods for detecting micrometastasis. This was a
      pilot study to determine whether cytokeratin staining of LN from endometrial
      cancer patients is more sensitive than traditional histopathologic evaluation for
      the detection of micrometastasis. METHODS: The inclusion criteria included
      patients with surgical stage I-II endometrial cancer having >50% myometrial
      invasion, lesions >2 cm, and negative LN together with one of the following: FIGO
      grade 3 or cervical or lymph-vascular involvement. A matched control group
      included patients with LN metastasis. The evaluation of the LN at the time of
      initial surgery consisted of a frozen section and a reevaluation on permanent
      sections with H&E. In the study, lymphadenectomy specimens were cut, stained
      again with H&E and with cytokeratin, and examined. Cytokeratin staining was
      performed with AE1/AE3 antibodies. There were 16 LN-negative cases and 9 LN
      positive controls. RESULTS: There was complete agreement between the LN
      assessment at time of surgery and the study H&E review prior to the staining for
      cytokeratin. However, 2 LN-negative cases (12.5%) had micrometastasis by
      cytokeratin staining. One of these patients developed recurrent disease in the
      para-aortic LN and died of disease at 2.8 years. CONCLUSION: Cytokeratin staining
      may improve the sensitivity for detection of metastasis compared to traditional
      evaluation. This study strongly suggests that these micrometastasis are
      clinically significant. An approach incorporating cytokeratin analysis could
      improve the risk assessment of specific patients.

PMID- 14675671
TI  - Nuclear morphometric changes and therapy monitoring in patients with endometrial
      hyperplasia: a study comparing effects of intrauterine levonorgestrel and
      systemic medroxyprogesterone.
AB  - OBJECTIVE: To show that local application of the levonorgestrel intrauterine
      device was a better therapy for endometrial hyperplasia (EH) compared to per-oral
      gestagen treatment based on subjective (WHO criteria) and objective (prognostic
      data-based morphometric and stereological method/D score, predicting the risk of
      cancer development for each single patient) evaluation. METHODS: Women between 30
      and 70 years with EH and D score > 0 were treated with levonorgestrel
      intrauterine device (n = 26) and the results compared to a historic group of
      women treated with per-oral gestagen (n = 31). In both treatment groups only
      patients with low risk (D score > 1) and uncertain risk (D score = 0-1) of cancer
      development were included. Endometrial specimens were investigated prior to
      treatment and after 3 months of therapy. The endometrial samples from the two
      groups were examined by light microscopy and objective data-based morphometry to
      assess tissue characteristics and to evaluate nuclear size variation. RESULTS:
      After 3 months all patients treated with levonorgestrel intrauterine device
      showed regression of hyperplasia, whereas 14 of 31 patients in the per-oral group
      still had persisting disease. The objective morphometric analysis showed
      reduction in nuclear size for both treatment groups, including the D score > 1 as
      well as the D score 0-1 patients. However, the reduction was most obvious for the
      levonorgestrel intrauterine device-treated patients with initial D score of 0-1.
      CONCLUSION: The present study indicates that levonorgestrel intrauterine device
      is a superior alternative to per oral treatment of endometrial hyperplasia. By
      using objective morphometric treatment monitoring we have shown that the
      hyperplasia patients with the highest malignant potential (D score = 0-1) were
      those taking most benefit from local high-dose levonorgestrel therapy.

PMID- 14675672
TI  - Laparoscopic radical hysterectomy for invasive cervical cancer: 8-year experience
      of a pilot study.
AB  - OBJECTIVE: The aim of this study was to retrospectively evaluate, in a series of
      50 consecutive patients, the feasibility, morbidity, and survival outcome of the
      laparoscopic radical hysterectomy for carcinoma of the uterine cervix. METHODS:
      Fifty patients with invasive cervical cancer were operated on by laparoscopic
      radical hysterectomy between 1993 and 2001 at two cancer centers. Patients in a
      good general condition with a cervical carcinoma less than 4 cm and a body mass
      index up to 29 were eligible. Thirty-one patients had prior brachytherapy.
      RESULTS: The median overall operative time was 258 min. The mean number of
      harvested pelvic external iliac nodes was 13.22 per patient. The median
      postoperative hospital stay was 7.5 days. Two patients had major urinary
      complications; one had a bladder fistula and one a ureteral stenosis. The median
      follow-up was 44 months. The overall 5-year survival rate of FIGO stage Ia2 and
      Ib1 patients was 96%. CONCLUSION: Our results demonstrate that radical
      hysterectomy can be performed by laparoscopy in stage IB1 or less advanced node
      negative cervical cancer patients without compromising survival. Prior
      brachytherapy did not affect the feasibility of this radical procedure.

PMID- 14675673
TI  - Pilot study of vaginal plethysmography in women treated with radiotherapy for
      gynecological cancer.
AB  - OBJECTIVE: After pelvic radiotherapy for gynecological cancer, changes in the
      vaginal epithelium might influence sexual arousal and satisfaction, leading to
      dyspareunia and relational problems. The aim of the study was to determine the
      feasibility of vaginal plethysmography in order to measure physical late effects
      of this therapy on sexual function. METHODS: Patients treated with radiotherapy
      for cervical, endometrial, or ovarian cancer, who were in complete remission for
      over 1 year, underwent vaginal plethysmography to measure changes in vaginal
      vasocongestion, while watching erotic video fragments. Afterward two
      questionnaires, designed to measure feelings of sexual arousal during the video,
      and to identify sexual dysfunction, were completed. The results were compared
      with those of healthy women. RESULTS: Patients (n = 9) and volunteers (n = 8) did
      not differ in baseline amplitude of plethysmography and showed comparable changes
      in vaginal vasocongestion during the various video fragments. The decline in
      amplitude during the last video fragment in the patient group did not reach
      significance, but the group of patients is small and heterogeneous. Addressing
      subjective sexual arousal during the video, patients reported less feelings of
      lust and desire and fewer bodily sensations while watching than the controls.
      Patients worried more about the sexual satisfaction of their partners than
      controls. CONCLUSION: Vaginal plethysmography can be used to measure vaginal
      vasocongestion in patients treated with radiotherapy to the proximal vagina. In
      this pilot study the changes of vaginal vasocongestion during sexual arousal
      between patients and healthy volunteers were not different. This correlates with
      a comparable sexual satisfaction, although patients reported less feelings of
      lust.

PMID- 14675674
TI  - Is there a prognostic difference between depth of myometrial invasion and the
      tumor-free distance from the uterine serosa in endometrial cancer?
AB  - OBJECTIVE: The objective was to determine whether tumor-free distance from the
      uterine serosa is more predictive of patient outcome than depth of endometrial
      cancer invasion into the myometrium. METHODS: Patients with surgically staged
      endometrial adenocarcinoma between 1997 and 2000 were identified. Depth of
      myometrial invasion (DOI) was identified defined as the distance between
      endometrial-myometrial junction and deepest myometrial invasion. Tumor-free
      distance from the uterine serosa (TFD) was defined as the distance between the
      serosa and deepest myometrial invasion. DOI and TFD were expressed as continuous
      variables and compared with traditional surgicopathologic variables, recurrence,
      and survival to determine their predictive and prognostic significance. RESULTS:
      We identified 153 patients who met study criteria. The median DOI was 0.5 cm and
      the median TFD was 1.4 cm. The most common stage was IB, and 23 patients had
      positive nodes. With a median follow-up of 29 months, 10 patients have recurred.
      When DOI and TFD were compared in a univariate model, TFD was an equal or more
      significant predictor of traditional surgicopathologic variables. TFD but not DOI
      was predictive of recurrence. Likewise, TFD was a more significant predictor of
      dying from disease than DOI. In a multivariate model, TFD was shown to correlate
      with surgicopathologic variables, recurrence risk, and survival. DOI, however,
      was not predictive unless myometrial thickness was included in the model. A TFD
      of 1 cm maximized the balance of sensitivity and specificity in predicting
      recurrence. CONCLUSION: TFD as a single measurement carries significant
      prognostic importance in women with comprehensively staged endometrial cancer.

PMID- 14675675
TI  - Treatment of high-risk gestational trophoblastic neoplasia with etoposide,
      methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy.
AB  - OBJECTIVE: The objective of the study was to evaluate the efficacy and toxicity
      of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA
      CO) chemotherapy for the treatment of high-risk gestational trophoblastic
      neoplasia. METHODS: Forty-five patients with high-risk gestational trophoblastic
      tumors received 257 EMA-CO treatment cycles between 1986 and 2001. Twenty-five
      were treated primarily with EMA-CO because of the presence of one or more high
      risk factors and 20 were treated with EMA-CO secondarily after failure of single
      agent chemotherapy. Patients who had incomplete responses or developed resistance
      to EMA-CO were treated with drug combinations employing cisplatin and etoposide
      with or without bleomycin or ifosfamide. Adjuvant surgery and radiotherapy were
      used in selected patients. Survival, clinical response, and toxicity were
      analyzed retrospectively. RESULTS: The overall survival rates was 91% (41/45);
      survival rates were 92% (23/25) for primary treatment and 90% (18/20) for
      secondary treatment with EMA-CO. Of the 45 patients treated with EMA-CO, 32 (71%)
      had a complete clinical response, 9 (20%) developed resistance but were
      subsequently placed into remission with cisplatin-based chemotherapy, and 4 (9%)
      died of widespread metastatic disease. Clinical complete response to EMA-CO was
      significantly influenced by duration of disease from antecedent pregnancy to
      treatment (<6 months, 84%, vs >6 months, 43%), metastatic site (lung and pelvis,
      73%, vs other, 40%), and WHO score (< or =7, 96%, vs >7, 36%). The EMA-CO
      chemotherapy regimen produced no life-threatening toxicity, caused grade 3-4
      hematologic toxicity in 1.6% of cycles, and was associated with neutropenia
      necessitating a 1-week delay in treatment in only 13.5% of cycles. CONCLUSION:
      EMA-CO chemotherapy is a well-tolerated and highly effective treatment for high
      risk gestational trophoblastic neoplasia, yielding a 71% complete response rate
      and a 91% survival rate in this series.

PMID- 14675676
TI  - Adenosquamous histology predicts poor outcome in low-risk stage IB1 cervical
      adenocarcinoma.
AB  - OBJECTIVE: The purpose of this study was to identify poor prognostic factors of
      low-risk stage IB1 cervical adenocarcinoma METHODS: . All women diagnosed with
      stage IB1 cervical adenocarcinoma between 1982 and 2002 were identified at our
      three institutions. Data were extracted from medical records. Patients were
      retrospectively assigned to a low- or intermediate/high-risk cohort based on the
      surgical-pathologic eligibility criteria of two randomized controlled trials of
      adjuvant therapy in early stage cervical cancer, Gynecologic Oncology Group
      protocols 92 and 109. Multivariate analysis was performed. RESULTS: Two hundred
      thirty women diagnosed with stage IB1 cervical adenocarcinoma had an overall 5
      year survival of 89%. Adenosquamous cell type (P < 0.01) was the only independent
      risk factor of disease recurrence in the low-risk group (n = 178). The 5-year
      disease-free survival for low-risk adenosquamous patients was 79%, compared to
      96% for other histologic subtypes (P < 0.01). Low-risk case subjects developed
      fewer disease recurrences than those in the intermediate/high-risk (n = 52)
      category (7% vs 46%; P < 0.01). The 5-year disease-free survival for
      intermediate/high-risk patients was 51% and no additional risk factors were
      identified. CONCLUSION: Adenosquamous histology is predictive of disease
      recurrence and decreased survival in low-risk stage IB1 cervical adenocarcinoma.
      This risk factor should be considered in future clinical trials of adjuvant
      therapy.

PMID- 14675677
TI  - Long-term follow-up of women with ovarian cancer after positive second-look
      laparotomy.
AB  - OBJECTIVE: Previous reports indicate that cytoreduction and salvage therapy with
      P32 or whole abdominal radiation may improve survival in patients with positive
      findings at second-look laparotomy (SLL). The aim of this investigation was to
      determine whether these findings held true with extended follow-up and a larger
      patient cohort. METHODS: From 1977 (the year platinum-based chemotherapy was
      introduced to our institution) to 1989, 150 patients had persistent disease at
      SLL. Relevant clinical information was extracted through retrospective chart
      review. RESULTS: One hundred forty-five patients were followed until death, with
      a median follow-up of 15.4 years for the 5 living patients. Median actuarial
      survival from the time of SLL was 18 months. Tumor grade (P = 0.003) and pre- and
      post-SLL tumor size (P < 0.0001) were significant determinants of survival by
      univariate analysis. Patients with microscopic disease or those with < or =1 cm
      disease rendered microscopic at SLL had improved survival relative to those with
      < or =1 cm and macroscopic disease following SLL (P = 0.03) (median survivals of
      3.3, 2.5, and 1.4 years, respectively). In contrast, median survival of those
      with >1 cm disease cytoreduced to microscopic disease was no different than those
      with macroscopic residual, even if < or =1 cm (1.3 and 1.0 years, respectively).
      After adjusting for tumor size, salvage treatment was not a significant predictor
      of survival. CONCLUSION: With long-term follow-up there was no suggestion that
      the type of salvage therapy (e.g., P32 or WART) influenced survival. Rather, low
      grade disease and low tumor burdens following cytoreduction were associated with
      improved survival on multivariate analysis.

PMID- 14675678
TI  - Implementation of assisted reproductive technologies following conservative
      management of FIGO grade I endometrial adenocarcinoma and/or complex hyperplasia
      with atypia.
AB  - OBJECTIVE: The objective was to report a series of infertility therapy outcomes
      following conservative management of endometrial adenocarcinoma and/or complex
      hyperplasia with atypia. METHODS: A retrospective review of the University of
      Iowa assisted reproductive technology database was performed. All women
      presenting with International Federation of Obstetrics and Gynecology (FIGO)
      grade I uterine adenocarcinoma and/or complex hyperplasia with atypia were
      assessed for type and duration of medical management, initial, interim treatment,
      and preinfertility treatment endometrial biopsy (BX) findings. Assessment of
      infertility treatment outcomes and postinfertility endometrial biopsy findings
      were performed. All of the pathology samples were re-reviewed at the Gynecologic
      Oncology Tumor Board to confirm the diagnosis by a pathologist with a particular
      expertise in gynecologic pathology. RESULTS: Four infertile women, three
      nulligravid and one primigravid, were evaluated with the diagnosis of FIGO grade
      1 endometrial adenocarcinoma and/or complex hyperplasia with atypia desiring to
      preserve fertility. Two women with FIGO grade 1 endometrial adenocarcinoma were
      successfully treated with high-dose progestational agents resulting in normal
      proliferative endometrium. In addition, both women with complex hyperplasia with
      atypia were successfully treated with progestins and/or ovulation induction.
      Successful pregnancy outcomes were achieved for three of the four women with
      assisted reproductive technology. A total of five successful pregnancies and
      eight healthy live-born infants were achieved among three women. One of the four
      women was unable to conceive despite three cycles of in vitro fertilization.
      Hysterectomy was performed for recurrent complex hyperplasia with atypia. In our
      series, we found it can take 3-10 months (mean, 6.25 months; median, 6 months) to
      obtain benign endometrium preceding infertility therapy. CONCLUSION: This report
      demonstrates that conservative management of well-differentiated endometrial
      adenocarcinoma and/or complex hyperplasia with atypia followed by aggressive
      assisted reproduction is an option to highly motivated and carefully selected
      women.

PMID- 14675679
TI  - Phase 2 trial of single agent docetaxel in platinum and paclitaxel-refractory
      ovarian cancer, fallopian tube cancer, and primary carcinoma of the peritoneum.
AB  - OBJECTIVE: Previously reported data have suggested the lack of complete cross
      resistance between docetaxel and paclitaxel in ovarian cancer. We wished to
      evaluate the biological and clinical activity of docetaxel in a patient
      population with well-characterized platinum and paclitaxel-refractory ovarian
      cancer. METHODS: In this single-institution phase 2 trial, 30 women with advanced
      ovarian cancer whose disease had either failed to respond to primary platinum
      paclitaxel chemotherapy or where the cancer had progressed within 3 months of
      their last treatment with both a platinum agent and paclitaxel were treated with
      single agent docetaxel (75 mg/m(2) q 3 weeks). Due to a prior history of
      excessive chemotherapy-induced neutropenia, 3 patients initiated treatment at a
      dose of 60 mg/m(2). RESULTS: The median number of courses of docetaxel delivered
      on this protocol was 3 (range 1-7), with 7 patients requiring dose reductions due
      to treatment-related side effects. The most common toxicities included grade 4
      neutropenia, neutropenic fever, and grade >/=2 fatigue experienced by 9 (30%), 2
      (7%), 5 (17%) patients, respectively. Three patients (10%) achieved both an
      objective response (by CA-125 criteria) and symptomatic improvement (e.g.,
      decrease in pain and ascites). The durations of responses were 3, 4, and 6
      months. CONCLUSION: Single-agent docetaxel has modest, but definite activity in
      patients with well-characterized platinum and paclitaxel-resistant ovarian
      cancer. Use of this drug should be considered a rational management approach in
      appropriately selected patients in this clinical setting.

PMID- 14675680
TI  - Characterization of human cervical precancerous tissue through the fourier
      transform infrared microscopy with mapping method.
AB  - OBJECTIVE: The aim of this study was to evaluate directly the utility of Fourier
      transform infrared microscopy (FTIR-MC) in detecting cervical precancer by
      comparison with the pathological examination of biopsy tissue. METHODS: Cervical
      biopsy specimens were obtained from the outpatient department at Kaohsiung
      Municipal Ta-Tung Hospital. Freshly isolated tissue was washed in isotonic saline
      and then frozen for use. Two successive slices were cut with a microtome. One
      unstained slice was used for reflectance FTIR-MC analysis; the other slice was
      stained with hematoxylin and eosin and used for position reference by microscopic
      mapping. RESULTS: The spectral region from 950 to 1500 cm(-1) is the most
      critical region in the IR spectrum of the tissue. There were two special peaks
      that had growth and decline in the IR spectra. The one at 1150 cm(-1) disappeared
      and the other at 1240 cm(-1) broadened when the tissue had pathological changes.
      From the results, we found that the ratio of the areas of the two regions between
      1130 to 1180 cm(-1) and 1180 to 1260 cm(-1) was an exceptionally useful factor in
      discriminating precancerous tissues from normal tissues. CONCLUSION: We carried
      out microscopic mapping of the tissues and demonstrated that the color map
      reflects pathological changes in the cervical tissues.

PMID- 14675681
TI  - Treatment of recurrent ovarian cancer: a retrospective analysis of women treated
      with single-agent carboplatin originally treated with carboplatin and paclitaxel.
      The Memorial Sloan-Kettering Cancer Center experience.
AB  - OBJECTIVE: There is no standard treatment for recurrent epithelial ovarian cancer
      (EOC). As there are no curative options, many oncologists choose to treat women
      who recur with carboplatin, particularly if they are deemed to have platinum
      sensitive disease. However, particularly in the era of platinum-taxane treatment
      as primary therapy, the utility of this treatment has not been established, nor
      is it clear whether the results of single-agent treatment are equivalent to that
      of combination therapy. We sought to determine the outcomes for patients with
      platinum-sensitive EOC who were treated with carboplatin-taxane therapy and
      received single-agent carboplatin (C) as second chemotherapy. In addition, we
      sought to compare these results to the outcomes in women who received carboplatin
      and paclitaxel (C + T) at first relapse. PATIENTS AND METHODS: We identified 24
      patients using our electronic institutional database with a histologically
      confirmed diagnosis of ovarian cancer that had a complete response to platinum
      paclitaxel chemotherapy, relapsed greater than 6 months after treatment, and
      received single-agent carboplatin as second-line chemotherapy. We performed a
      subsequent comparison between a subgroup of this cohort and one that met the same
      inclusion criteria but received C + T at relapse between January 1998 and
      December 2000. RESULTS: Eighteen patients were evaluable for response, and all
      were available for analysis of survival end points. For evaluable patients, the
      overall response rate was 39% (complete, 11%; partial, 28%). Twenty-two percent
      had stable disease. Six (25%) patients experienced a hypersensitivity reaction,
      including 1 who required hospitalization. The median overall survival was 22
      months. The 2-year overall survival rate was 49%. Stratification by treatment
      free interval (TFI) showed a 25% for a TFI between 6 and 12 months and 43% for a
      TFI > 12 months. When a subgroup of these women (18/24) was compared to a cohort
      that received C + T (29), the combination was associated with a higher complete
      and overall response rate, 7 and 36% for C versus 45 and 71% for C + T (P =
      0.02). The overall survival in women who received C was 26 months versus 42
      months in the women who received C + T (P < 0.02). CONCLUSION: Carboplatin as a
      single agent is effective therapy for recurrent ovarian cancer in women who recur
      following treatment with carboplatin and paclitaxel, and the treatment-free
      interval predicts response to single-agent carboplatin. However, our secondary
      analysis suggests that carboplatin and paclitaxel may produce a higher response
      rate and a survival benefit compared to C alone. This supports the conclusions of
      ICON4, which recently reported both overall and progression-free survival
      benefits with C + T over C in women with platinum-sensitive recurrent disease.

PMID- 14675682
TI  - Complications of indwelling venous access devices in patients with gynecologic
      malignancies.
AB  - OBJECTIVE: The purpose of this study was to evaluate the complication rates
      associated with indwelling venous access devices in patients with gynecologic
      malignancies. METHODS: Following IRB approval, a computerized database identified
      women that had indwelling access devices placed for chemotherapy from March 1999
      to June 2001. A retrospective chart review identified 116 venous access devices
      that were placed in 104 patients. All devices were silicone and had a closed tip
      design with a three-position valve. Data were collected on patient demographics,
      clinicopathologic features, type of venous device, and complications. The chi(2)
      test was used for statistical analysis. RESULTS: Of the 104 patients, 79 had
      ovarian cancer, 11 had uterine cancer, 10 had cervical cancer, 2 had fallopian
      tube cancer, and 2 had vaginal cancer. The median age was 61 years. There were a
      total of 116 venous devices placed: 65 external catheters (EC) and 51
      subcutaneous ports (SP). Seventy-nine percent of the patients were administered
      low-dose coumadin (1 mg/day) for catheter clot prophylaxis. There were three
      operative complications in the EC group and two in the SP group (P = NS). The
      most common postoperative complications were infection and thrombosis. Nineteen
      patients in the EC group experienced a catheter-related infection versus 5 in the
      SP group (P = 0.025). In the EC group, there were 11 cases of site infection and
      8 cases of line sepsis. In contrast, there were 3 cases of exit site infection
      and 2 cases of line sepsis in the SP group. Deep vein thrombosis occurred in 5
      patients with EC and 3 patients with SP (P = NS). Twenty-seven patients with EC
      had the device removed for catheter-related complications versus 2 patients with
      SP (P = 0.001). Six patients inadvertently removed their EC. CONCLUSION: There is
      a significantly higher postoperative complication rate in gynecologic oncology
      patients with external catheters versus subcutaneous ports. Infection and
      catheter-related malfunction are more common in patients with external catheters.
      We recommend the use of subcutaneous ports in the majority of patients with
      gynecologic malignancies.

PMID- 14675683
TI  - Phase II trial of anastrozole in women with asymptomatic mullerian cancer.
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of the selective aromatase
      inhibitor anastrozole (Arimidex), we conducted a phase II trial in 53 women with
      asymptomatic recurrent/persistent mullerian cancer. METHODS: Patients with
      ovarian, peritoneal, or fallopian tube carcinoma were eligible for enrollment.
      Eligible patients had an ECOG PS < or = 1 and no clinical indication for
      immediate systemic chemotherapy. Patients were assigned to measurable (cohort 1)
      or evaluable disease (cohort 2) cohorts, respectively. Patients were treated with
      anastrozole 1 mg po daily. Monthly follow-up included interim history, physical
      exam, and CA-125 with radiologic evaluation every 3 months. Estrogen,
      progesterone, and Her-2/neu receptor status was also evaluated in archived tumor
      samples. RESULTS: Fifty-three women with a median age of 63 (range, 46-86) years
      were enrolled. Twenty-nine women enrolled in cohort 1 and 24 in cohort 2.
      Included were 43, 7, and 3 women with ovarian, primary peritoneal, and fallopian
      tube carcinoma, respectively. All 53 patients were evaluable for treatment
      toxicity and response. The median time to disease progression was 85 days (85
      days for cohort 1 and 82 days for cohort 2). A partial response was documented in
      a single patient with measurable disease. Forty-two percent of patients had
      stable disease (measured as time to treatment termination) for >90 days, 15% for
      >180 days, 7% for >270 days, and 4% for >360 days. One patient remained on
      anastrozole at 15 months. Toxicity was modest (grade I) and infrequent, with the
      most common toxicities being fatigue and hot flashes. There were no thrombotic
      complications. Median time to progression for patients with estrogen receptor
      positive tumors was 72 days as compared to 125 days for those with tumors
      negative for the estrogen receptor (P = 0.95, log-rank test). The median time to
      progression in patients with progesterone-positive tumors was 77 days and 91 days
      for patients with progesterone-negative tumors. CONCLUSION: In summary,
      anastrozole is a well-tolerated oral agent but with minimal tumoricidal activity
      in women with recurrent/persistent mullerian cancers. A minority of patients
      demonstrated prolonged stable disease while on this agent.

PMID- 14675684
TI  - A retrospective review on atypical glandular cells of undetermined significance
      (AGUS) using the Bethesda 2001 classification.
AB  - OBJECTIVE: The Bethesda system for reporting cervicovaginal cytologic diagnoses
      was recently revised in 2001. Pathologists are required to report not only
      whether the smear favors neoplastic changes, but also the origin of the abnormal
      cells. In this study, archival smears were reviewed to evaluate the usefulness of
      the new classification. METHODS: Smears having atypical glandular cells taken
      between January 1995 and December 1997 were reviewed and subclassified according
      to the revised Bethesda classification. Case records were then reviewed and cases
      with discrepancies between the cytological evaluation and corresponding final
      histological diagnoses were further reviewed. RESULTS: There were 138 smears
      reviewed. The mean age of the patients was 47 (range, 18 to 78). Thirty-four
      smears favored neoplasia and 104 favored "NOS" ("not otherwise specified"). Sixty
      smears favored endocervical origin and 78 endometrial origin. Forty-three
      patients (31%) had significant pathologies, including 12 (8.7%) patients with
      high-grade CIN, 2 (1.4%) with low-grade CIN, 5 (3.6%) with HPV infection, 7
      (5.1%) with carcinoma of the corpus, 1 (0.7%) with cervical adenocarcinoma in
      situ, 4 (2.9%) with adenocarcinoma of the cervix, 3 (2.2%) with endometrial
      hyperplasia, and 5 (3.6%) with carcinoma of the ovary. Two (1.4%) patients had
      double primary female genital malignancies and 2 patients (1.4%) had extragenital
      malignancies. Significant correlation was found between smears "favor neoplasia"
      and a final diagnosis with significant pathology (chi(2) test, P < 0.05).
      Significant association was found between AGC favored endocervical origin and a
      final diagnosis with cervical diseases (chi(2) test, P < 0.05). Four of the 43
      patients who had significant pathologies had lesions found during their
      subsequent visits and all of them had cervical smears classified as AGC "favor
      neoplasia". CONCLUSION: AGC found on cervical smears are an indication for early
      and intensive investigation.

PMID- 14675685
TI  - Survival of Californian women with epithelial ovarian cancer, 1994-1996: a
      population-based study.
AB  - OBJECTIVE: The objective was to identify demographic, clinical, and provider
      characteristics that might influence cancer survival in a cohort of Northern
      California women using a population-based cancer registry. METHODS: We used
      California Cancer Registry data to evaluate survival in 1051 Northern California
      women who were diagnosed with epithelial ovarian cancer between 1994 and 1996 and
      underwent a surgical procedure for their cancer. Chemotherapy data from the
      cancer registry were supplemented with a physician survey and medical record
      review. Database linkages with census and hospital discharge data provided
      socioeconomic and comorbidity measures. Kaplan-Meier method was used to generate
      survival curves and multivariate Cox proportional hazard models were used to
      evaluate the effect of different factors on survival. RESULTS: Crude 5-year
      survival was 82, 57, 28, and 10% for women with FIGO stage IC, II, III, and IV
      disease, respectively. Adverse survival was most strongly influenced by advanced
      stages III and IV with a hazards ratio ranging from 8 to 11.8 compared to stage
      IC disease. Multivariate analysis also identified other adverse factors including
      high grade and other adverse histologies, age over 45, and rural location.
      Chemotherapy decreased the risk of death by 50% if the patient had advanced-stage
      disease. Medical comorbidity increased the risk of death by 40%. Survival was not
      influenced by race/ethnicity, socioeconomic status, physician specialty, or
      hospital characteristics. CONCLUSION: Advanced age remains an adverse prognostic
      factor even after adjustment for treatment and comorbidity factors. These results
      also suggest that there may be important regional differences in ovarian cancer
      survival.

PMID- 14675686
TI  - Laparoscopic total pelvic exenteration for cervical cancer relapse.
AB  - BACKGROUND: Laparoscopy classically reduces morbidity and invasiveness. To
      decrease the operative morbidity associated with exenteration, we considered the
      possibility of performing a total pelvic exenteration by the laparoscopic
      approach. CASE: A 34-year-old woman presented with a cervical cancer relapse. The
      bladder, uterus, vagina, ovaries, and rectum were mobilized en bloc from the
      pelvic sidewall. We used vascular endoscopic staplers for the control of sigmoid
      vessels and anterior branches of internal iliac vessels. The specimen was removed
      through the vulva. A colo-anal anastomosis and an ileal-loop conduit for urinary
      tract diversion were made. The operative time was 9 h. The postoperative course
      was uneventful. Specimen margins were free of disease. CONCLUSION: With
      laparoscopic surgical knowledge and new endoscopic staplers, laparoscopic pelvic
      exenteration procedure is feasible.

PMID- 14675687
TI  - Laparoscopic-assisted radical parametrectomy including pelvic and/or paraaortic
      lymphadenectomy in women after prior hysterectomy-three cases.
AB  - BACKGROUND: Radical abdominal surgery in patients who have previously undergone a
      hysterectomy is a surgical challenge. This type of surgery for invasive cervical
      cancer after a hysterectomy or vaginal stump metastasis traditionally requires a
      major laparotomy; however, a minimal-access approach is now being applied to this
      type of procedure. CASE: A laparoscopic-assisted radical parametrectomy including
      a pelvic and/or paraaortic lymphadenectomy was performed on two patients
      presenting invasive cervical cancer diagnosed after a simple hysterectomy and one
      patient with recurred endometrial cancer in the vaginal stump. All three patients
      had an excellent clinical outcome and made a rapid recovery with no major
      complications, even though two cases involved a bladder laceration. CONCLUSION: A
      laparoscopic radical parametrectomy including a pelvic and/or paraaortic
      lymphadenectomy is a viable technique for women with invasive cervical cancer or
      recurrent endometrial vaginal cancer after a prior hysterectomy.

PMID- 14675688
TI  - Alveolar rhabdomyosarcoma of the cervix.
AB  - BACKGROUND: Alveolar rhabdomyosarcoma (RMS) has a high risk for local and distal
      failure. Multimodal management of a patient with alveolar RMS of the cervix uteri
      is outlined. CASE: A 39-year-old woman suffered from alveolar RMS of the cervix
      without involvement of uterus and parametrium. She was treated with total
      hysterectomy and left salpingo-oophorectomy. Systemic chemotherapy and pelvic
      irradiation were also offered. She remains in clinical remission 3 years after
      presentation. CONCLUSION: Postoperative chemotherapy and irradiation could be
      effective treatments for alveolar rhabdomyosarcoma of the cervix in adult
      patients.

PMID- 14675689
TI  - Primary vaginal leiomyosarcoma in pregnancy.
AB  - BACKGROUND: Primary vaginal sarcoma constitutes about 2% of all malignant vaginal
      lesions, with leiomyosarcoma being the most common in adult women. To our
      knowledge, this is the first case of vaginal leiomyosarcoma occurring during
      pregnancy. CASE: A 21-year-old woman, at 39 weeks of gestation, presented with a
      pedunculated vaginal mass. Local excision of the mass was performed immediately.
      Histopathologic evaluation revealed a grade 2 leiomyosarcoma. The patient
      delivered a healthy infant 2 weeks after resection. She has had no evidence of
      recurrence in 28 months of follow-up. CONCLUSION: Previous cases of vaginal
      leiomyosarcoma and sarcomas of the female genital tract occurring during
      pregnancy are reviewed. The histopathologic criteria for vaginal smooth muscle
      tumors are well established. Primary management of vaginal leiomyosarcoma is
      surgical.

PMID- 14675690
TI  - Gastrointestinal stromal tumor presenting as a pelvic mass.
AB  - Gastrointestinal stromal tumors (GISTs) are c-kit-positive tumors that may arise
      anywhere in the tubular gastrointestinal tract. Around 5% of the cases arise
      elsewhere in the abdominal cavity. Tumors originating in the omentum and
      mesentery have been reported.A 31-year-old woman presented with pelvic pain, a
      palpable pelvic mass, and elevated CA-125. Imaging showed innumerable pelvic and
      abdominal masses. Histopathology showed a GIST that was positive for c-kit and
      vimentin and negative for desmin and smooth muscle actin. The patient was started
      on imatinib mesylate. Six months after diagnosis the tumor has remained stable.GI
      stromal tumors (GIST) may initially present as pelvic mass with elevated CA-125.
      Imatinib mesylate is the current mainstay therapy for GISTs after surgery.

PMID- 14675691
TI  - Leiomyosarcoma of the cervix.
AB  - BACKGROUND: Epithelioid leiomyosarcoma arising from the uterine cervix is
      extremely rare, with only three cases reported in the world literature. We
      present the case report of a 14-cm epithelioid leiomyosarcoma arising from the
      uterine cervix. CASE: A 47-year-old female presented with a 1-year history of
      worsening menorrhagia and was found to have a large pelvic mass extending into
      and filling the upper vagina. She underwent total abdominal hysterectomy and
      bilateral salpingo-oophorectomy, revealing a 14 x 10 x 9 cm cervical epithelioid
      leiomyosarcoma. CONCLUSION: Although exceedingly rare, leiomyosarcoma is able to
      arise primarily from the uterine cervix. Given its extreme rarity, management of
      cervical LMS must be extrapolated from the currently accepted management for
      uterine LMS.

PMID- 14675692
TI  - Ovarian endometrioid adenocarcinoma arising from endometriosis in a young woman.
AB  - BACKGROUND: The risk of ovarian cancer increases in women with a long history of
      ovarian endometriosis, particularly in postmenopausal women. We present here a
      case of malignant transformation of endometriosis occurring over a short time in
      a young woman. CASE: The 27-year-old woman underwent laparoscopic cystectomy and
      was diagnosed with left ovarian endometrioma with an accompanying high level of
      serum CA125 (734.6 U/mL). Fourteen months later, she underwent cytoreductive
      surgery for her ovarian cancer. Histological examination revealed endometrioid
      adenocarcinoma with transitions between endometriosis and adenocarcinoma. She was
      diagnosed as having stage IIIc of ovarian cancer with paraaortic lymphnode
      involvement. CONCLUSION: We suggest that endometrial cyst of the ovary associated
      with high levels of serum CA125 should be managed with special care even in a
      young woman.

PMID- 14675693
TI  - Massive ovarian edema revealing gastric carcinoma: a case report.
AB  - Tumor-like enlargement of the ovaries due to accumulation of edema fluid within
      the ovarian stroma is referred to as massive ovarian edema (MOE). The
      pathogenesis of MOE is thought to be intermittent torsion of the ovary on its
      pedicle, causing partial obstruction of venous and lymphatic drainage. The
      diagnosis of MOE is based on imaging techniques. The case described here due to
      ovarian lymphatic vessel obstruction by carcinoma cells shows that metastatic
      disease may be a cause of MOE.

PMID- 14675694
TI  - Steroids and adrenomedullin growth patterns in human ovarian cancer cells:
      estrogenic-regulation assay.
AB  - OBJECTIVE: Adrenomedullin is a multifunctional regulatory peptide with mitogenic
      and angiogenic capabilities. Objectives in this study were: (1) to describe the
      effects of adrenomedullin and anti-adrenomedullin antibodies on ovarian carcinoma
      cell proliferation, and (2) to assess the estradiol regulation of adrenomedullin
      metabolism. METHODS: We assessed the effects of estradiol, adrenomedullin, and
      anti-adrenomedullin antibodies on cell growth in three human ovarian cell lines.
      RT-PCR was used to assess mRNA expression and Western blots to determine protein
      levels. RESULTS: Estradiol stimulates BG-1 and PEO4 cells growth but not PEO14
      cells. Adrenomedullin mRNA expression and secretion were not under estrogen
      control. Adrenomedullin and anti-adrenomedullin antibodies had no growth effects
      in vitro. Adjunction of anti-adrenomedullin antibodies to estradiol-stimulated
      cells significantly inhibited their growth. CONCLUSION: Adrenomedullin metabolism
      is not under estradiol control. Anti-adrenomedullin antibodies display inhibitory
      effects on cells having high mitogenic activity. This opens the need for
      additional search toward in vivo specific immunotherapy.

PMID- 14675695
TI  - Performing a surgical procedure through midline incision is not a "surgical
      dogma" in some circumstances in gynecologic oncology.

PMID- 14675697
TI  - Ovarian conservation and hormone receptors in uterine Mullerian adenosarcomas.

PMID- 14675699
TI  - HSP60 and HSP10 as diagnostic and prognostic tools in the management of
      exocervical carcinoma.

PMID- 14675701
TI  - Acute pancreatitis: molecular biology update.

PMID- 14675702
TI  - Molecular pathophysiology of chronic pancreatitis--an update.

PMID- 14675703
TI  - Is extended resection for adenocarcinoma of the body or tail of the pancreas
      justified?
AB  - Patients with body or tail tumors of the pancreas often have contiguous organ
      involvement or portal-splenic confluence adherence requiring extensive resection
      in order to obtain grossly negative margins. The aim of this study was to
      determine whether long-term survival is possible after contiguous organ or portal
      vein resection in patients with adenocarcinoma of the body or tail of the
      pancreas. Between 1983 and 2000, a total of 513 patients with adenocarcinoma of
      the body or tail of the pancreas were identified from a prospective database.
      Distal pancreatectomy with or without splenectomy was performed in 57 patients
      (11%). Extended resection was necessary in 22 patients (39%): 14 (64%) for
      contiguous organ involvement and eight (36%) for portal vein resection Estimated
      blood loss, blood transfused, and length of hospital stay were significantly
      greater in patients requiring extended resection compared to standard resection
      (P=0.02, P=0.01, and P=0.02, respectively). Median follow-up for patients still
      alive was 84 months (range 40 to 189 months). Median survival following resection
      was 15.9 months compared to 5.8 months in patients who were not resected
      (P<0.0001). Actual 5- and 10-year survival rates were 22% and 18%, respectively,
      following extended resection, 8% and 8% following standard resection, and 0% and
      0% if no resection was attempted because of locally unresectable disease.
      Patients undergoing extended resection for adenocarcinoma of the pancreatic body
      or tail have long-term survival rates similar to those for patients undergoing
      standard resection; they also have markedly improved long-term survival compared
      to those who are not considered resectable because of locally advanced disease.
      Extended distal pancreatectomy is justified in this group of patients.

PMID- 14675704
TI  - 18-Fluorodeoxyglucose positron emission tomography in predicting survival of
      patients with pancreatic carcinoma.
AB  - The prediction of survival of patients with pancreatic cancer is usually based on
      tumor staging and grading and on the level of tumor markers. However, accurate
      tumor staging can be obtained only after resection, and still there is a great
      difference in survival rates among patients with the same clinicopathologic
      parameters. Recently the uptake of 18-fluorodeoxyglucose (FDG) by positron
      emission tomography (PET) has been found to be correlated with survival in
      patients with pancreatic cancer. This study evaluated the role of 18FDG PET as a
      prognostic factor for patients with pancreatic cancer. From June 1996 to July
      2002, a total of 118 patients underwent PET for pancreatic cancer. The
      standardized uptake value (SUV) of 18FDG was calculated in 60 of them, and these
      patients were divided into high (>4) and low (< or =4) SUV groups. They were also
      evaluated according to the tumor node metastasis (TNM) classification system of
      the International Union Against Cancer, and by tumor grade, medical or surgical
      treatment, diabetes, age, sex, and CA 19-9 serum levels. Twenty-nine cancers
      showed high and 31 showed low SUVs. Survival was significantly influenced by
      tumor stage (P=0.0001), tumor grade (P=0.01), and SUV (P=0.005). Multivariate
      analysis showed that only stage (P=0.001) and SUV (P=0.0002) were independent
      predictors of survival. When patients who were analyzed for SUV were stratified
      according to the other variables, FDG uptake was related to survival also after
      stratification for the following: stage III to IVa (P=0.002), stage IVb (P=0.01),
      tumor resection (P=0.006), moderately differentiated tumors (P=0.01), age less
      than 65 years (P=0.006), CA 19-9 levels greater than 300 kU/L (P=0.002), and
      absence of diabetes (P=0.0001). The SUV calculated with 18FDG PET is an important
      prognostic factor for patients with pancreatic cancer and may be useful in
      selecting patients for therapeutic management.

PMID- 14675705
TI  - Troponin I peptide (Glu94-Leu123), a cartilage-derived angiogenesis inhibitor: in
      vitro and in vivo effects on human endothelial cells and on pancreatic cancer.
AB  - Several inhibitors of angiogenesis have been identified in bovine and shark
      cartilage. One of them is troponin I, which is the molecule responsible for the
      inhibition of the actomyosin ATPase during muscle contraction. In this study we
      sought to investigate if the active site of troponin I (peptide Glu94-Leu123;
      pTnI) is also the one responsible for the antiangiogenic properties of this
      protein. The effects of pTnI on endothelial cell tube formation and endothelial
      cell division were investigated using human umbilical vein endothelial cells,
      Matrigel, light microscopy, carboxyfluorescein diacetate, succinimidyl
      esterlabeling, and flow cytometry. Its effects on induction of ICAM-1 and
      production of vascular endothelial growth factor by pancreatic cancer cells
      (CAPAN-1) were also investigated, as was its efficacy in a mouse model of
      pancreatic cancer metastases. Our results show that concentrations as low as 1
      pg/ml of pTnI significantly inhibit endothelial cell tube formation, and that
      endothelial cell division was inhibited at 96 hours by 3 microg/ml pTnI
      (P=0.0001). No effects were seen using troponin peptide 124-181 as a control.
      pTnI-treated supernatant from the pancreatic cancer cell line CAPAN-1
      downregulated ICAM-1 expression on human umbilical vein endothelial cells up to
      10 ng/ml pTnI, and a significant reduction in vascular endothelial growth factor
      production was seen by treating CAPAN-1 cells with up to 1 microg/ml pTnI. After
      intrasplenic injection of CAPAN-1 cells, mice treated with pTnI had fewer liver
      metastases compared to control mice (liver/body weight 5.5 vs. 11.1; P=0.03). The
      active region of troponin I is the one responsible for its antiangiogenic effect.
      The mechanism of action of this peptide is probably multifactorial.

PMID- 14675706
TI  - Cystic lesions of the pancreas: selection criteria for operative and nonoperative
      management in 209 patients.
AB  - Because of the inability to determine benign from malignant, many have
      recommended that all cystic lesions of the pancreas be resected. Patients
      evaluated between January 1995 and December 2000 for the ICD-9 diagnosis of
      pancreatic cyst (577.2) or benign neoplasm of the pancreas (211.6) were reviewed.
      Patient, cyst, and treatment characteristics were recorded. Comparisons were made
      between patients who underwent operative and nonoperative management. Over the 5
      year period, 209 patients were evaluated. Nonoperative treatment was initially
      chosen for 144 patients (69%). In this group the average cyst diameter was 2.5 cm
      (range 0.5 cm to 13.0 cm), and the median change in diameter during follow-up was
      zero cm (range 1.5 cm to 4.0 cm). In six patients (4%) changes occurred within
      the cyst that resulted in resection. None of these patients had a malignant
      diagnosis. Operative treatment was initially chosen for 65 (31%) of the 209
      patients. Malignancy was found in six of the operative patients (6 [9%] of 65).
      Differences in patient and cyst characteristics between groups included the cyst
      size, septations, a solid component, and the presence of symptoms. Selected
      patients with cystic lesions of the pancreas may be safely followed
      radiographically. Selection criteria identified in this study (symptoms, cyst
      size, solid component, and septations) and the utilization of new imaging
      techniques allow the creation of treatment plans for these patients that can be
      prospectively tested.

PMID- 14675707
TI  - Total pancreatectomy and autologous islet cell transplantation as a means to
      treat severe chronic pancreatitis.
AB  - Autologous islet cell transplantation after near-total or total pancreatic
      resection can alleviate pain in patients with severe chronic pancreatitis and
      preserve endocrine function. From February 2000 to February 2003, a total of 22
      patients, whose median age was 38 years, underwent pancreatectomy and autologous
      islet cell transplantation. Postoperative complications, metabolic studies,
      insulin usage, pain scores, and quality of life were recorded for all of these
      patients. The average number of islet cells harvested was 245,457 (range 20,850
      to 607,466). Operative data revealed a mean estimated blood loss of 635 ml, an
      average operative time of 9 hours, and a mean length of hospital stay of 15 days.
      Sixty-eight percent of the patients had either a minor or major complication.
      Major complications included acute respiratory distress syndrome (n=2), intra
      abdominal abscess (n=1), and pulmonary embolism (n=1). There were no deaths in
      our series. All patients demonstrated C-peptide and insulin production indicating
      graft function. Forty-one percent are insulin independent, and 27% required
      minimal amount of insulin or a sliding scale. All patients had preoperative pain
      and had been taking opioid analgesics; 82% no longer required analgesics
      postoperatively. Pancreatectomy with autologous islet cell transplantation can
      alleviate pain for patients with chronic pancreatitis and preserve endocrine
      function.

PMID- 14675708
TI  - Surgical management of hypertensive lower esophageal sphincter with dysphagia or
      chest pain.
AB  - Hypertensive lower esophageal sphincter (LES) is an uncommon manometric
      abnormality found in patients with dysphagia and chest pain, and is sometimes
      associated with gastroesophageal reflux disease (GERD). Preventing reflux by
      performing a fundoplication raises concerns about inducing or increasing
      dysphagia. The role of myotomy in isolated hypertensive LES is also unclear. The
      aim of this study was to determine the outcome of surgical therapy for isolated
      hypertensive LES and for hypertensive LES associated with GERD. Sixteen patients
      (5 males and 11 females), ranging in age from 39 to 89 years, with hypertensive
      LES (>26 mm Hg; i.e., >95th percentile of our control population) who had
      surgical therapy between 1996 and 1999 were reviewed. Patients with a diagnosis
      of achalasia and diffuse esophageal spasm were excluded. All patients had
      dysphagia or chest pain. Eight of 16 patients had symptoms of GERD, four had a
      type III hiatal hernia, and four had isolated hypertensive LES pain. Patients
      with hypertensive LES and GERD or type III hiatal hernia had a Nissen
      fundoplication, and those with isolated hypertensive LES had a myotomy of the LES
      with partial fundoplication. Outcome was assessed as follows: excellent if the
      patient was asymptomatic; good if symptoms were present but no treatment was
      required; fair if symptoms were present and required treatment; and poor if
      symptoms were unimproved or worsened. All patients were contacted by telephone
      for symptom assessment at a median of 3.6 years (range 3 to 6.1 years) after
      surgery. Patients with hypertensive LES and GERD or type III hiatal hernia had
      significantly lower LES pressure than those with isolated hypertensive LES (29.9
      vs. 47.4 mm Hg; P=0.013). Dysphagia and chest pain were relieved in all patients
      at long-term follow up. Outcome was excellent in 10 of 16, good in 3 of 16, and
      fair in 3 of 16. All patients but one were satisfied with their outcome. Patients
      with hypertensive LES are a heterogeneous group in regard to symptoms and
      etiology. Treatment of patients with hypertensive LES should be individualized. A
      Nissen fundoplication for hypertensive LES with GERD or type III hiatal hernia
      relieves dysphagia and chest pain suggesting reflux as an etiology. A myotomy
      with partial fundoplication for isolated hypertensive LES relieves dysphagia and
      chest pain suggesting a primary sphincter dysfunction.

PMID- 14675709
TI  - Incidence and outcome of anastomotic stricture after laparoscopic gastric bypass.
AB  - Anastomotic stricture is a frequent complication after Roux-en-Y gastric bypass
      (GBP). We evaluated the frequency of anastomotic stricture following laparoscopic
      GBP using a 21 mm. vs. a 25 mm circular stapler for construction of the
      gastrojejunostomy and the safety and efficacy of endoscopic balloon dilation in
      the management of anastomotic stricture. We reviewed data on 29 patients in whom
      anastomotic strictures developed after laparoscopic GBP. All strictures were
      managed with endoscopic balloon dilation using an 18 mm balloon catheter under
      fluoroscopic guidance. Main outcome measures were the number of anastomotic
      strictures in patients in whom the 21 mm (vs. 25 mm) circular stapler was used to
      create the gastrojejunostomy, time interval between the primary operation and
      symptoms, complications of endoscopic balloon dilation, the number of patients
      with resolution of obstructive symptoms, and body weight loss. There were 28
      females with a mean age of 39 years and a mean body mass index of 48 kg/m(2).
      Anastomotic stricture occurred significantly more frequently with the use of the
      21 mm compared to the 25 mm circular stapler (26.8% vs. 8.8%, respectively;
      P<0.01). The median time interval between the primary operation and presentation
      of stricture was 46 days. After the initial dilation, recurrent stricture
      developed in 5 (17.2%) of 29 patients. These five patients underwent a second
      endoscopic dilation, and only one of these five patients required a third
      endoscopic dilation. None of the 29 patients required more than three endoscopic
      dilations. The mean percentage of excess body weight loss at 1 year for patients
      in whom the 21 mm circular stapler was used for creation of the gastrojejunostomy
      was similar to that for patients in whom the 25 mm circular stapler was used
      (68.2% vs. 70.2%, P=0.8). In this series the rate of anastomotic stricture
      significantly decreased with the use of the 25 mm circular stapler for
      construction of the gastrojejunostomy without compromising weight loss.
      Endoscopic balloon dilation is a safe and effective option in the management of
      anastomotic stricture following laparoscopic GBP.

PMID- 14675710
TI  - Tumor suppressor gene hypermethylation as a predictor of gastric stromal tumor
      behavior.
AB  - The growing understanding of the epigenetic changes associated with cancer,
      including aberrant promoter methylation of tumor suppressor genes that afford
      selective growth advantages to human neoplasms, suggests that the
      characterization of gene methylation patterns among gastrointestinal stromal
      tumors (GISTs) may be useful for predicting tumor behavior. Thirty-eight c-kit
      positive gastric stromal tumors were subjected to methylation-specific polymerase
      chain reaction (MSP) to detect promoter methylation associated with 11 candidate
      tumor suppressor genes (p16/INK4a, APC, MGMT, hMLH1, p73, E-cadherin, RAR-beta,
      RASSF1A, RB, ER, and DAPK), established to have a role in tumorigenesis of
      several solid human organs. Aberrant methylation of any of the 11 candidate tumor
      suppressor genes was detected in 84% of all GISTs. In decreasing order of
      frequency, the six most commonly methylated genes were: MGMT (47%), p16 (45%),
      RASSF1A (40%), E-cadherin (37%), hMLH1 (34%), and APC (31%). For all of the
      GISTs, promoter methylation was less reliable than tumor mitotic rate in
      predicting 5-year tumor-free survival for the GISTs; however, E-cadherin
      methylation was a multivariate prognostic factor for early recurrence of GISTs
      (50% at 2 years; P=0.030). Among the mitotically active (>5 per 50 high-power
      field), histologically indistinguishable GISTs, E-cadherin methylation was an
      independent predictor of tumor-related mortality: 5-year disease-free survival
      was worse for the E-cadherin methylated GISTs (19%) compared to the E-cadherin
      unmethylated tumors (71%; P=0.010). Detection of methylation within selected
      genes may afford a reliable and accurate molecular marker system for predicting
      neoplastic behavior among GISTs. This study supports the methylation status of E
      cadherin as a prognostic marker for early GIST recurrence and survival.

PMID- 14675711
TI  - Complications of gastrectomy following CPT-11-based neoadjuvant chemotherapy for
      gastric cancer.
AB  - Potential benefits of neoadjuvant therapy for locally advanced gastric cancer
      include tumor downstaging and an increased R0 resection rate. Potential
      disadvantages include increased surgical complications. This study assesses
      postoperative morbidity and mortality by comparing patients undergoing
      gastrectomy with and without neoadjuvant chemotherapy. From October 1998 to July
      2002, a total of 34 patients with locally advanced gastric cancer were placed on
      a phase II neoadjuvant chemotherapy protocol consisting of two cycles of CPT-11
      (75 mg/m(2)) with cisplatin (25 mg/m(2)). Demographic, clinical, morbidity, and
      mortality data were compared for these patients (CHEMO) versus 85 patients
      undergoing gastrectomy without neoadjuvant chemotherapy (SURG). The CHEMO
      patients were more likely to be less than 70 years of age (P< or =0.01), have
      proximal tumors (P< or =0.01), and undergo proximal gastrectomy (P< or =0.025).
      Fifty-two percent of SURG patients had T3/T4 tumors compared to 19% of CHEMO
      patients, consistent with tumor downstaging. The R0 resection rate was similar
      (80%). Morbidity was 41% in CHEMO patients and 39% in SURG patients. There were
      five postoperative deaths (4.4%), two in the CHEMO group and three in the SURG
      group (P=NS). It was concluded that neoadjuvant chemotherapy with CPT-11 and
      cisplatin is not associated with increased postoperative morbidity compared to
      surgery alone. CPT-11-based neoadjuvant chemotherapy should be tested further in
      combined-modality treatment of gastric cancer.

PMID- 14675712
TI  - Novel combination of cyclooxygenase-2 and MEK inhibitors in human hepatocellular
      carcinoma provides a synergistic increase in apoptosis.
AB  - Cyclooxygenase-2 (COX-2) and ERK-MAPK mitogenic signaling pathways are important
      in human hepatocellular carcinoma. We investigated the effect of COX-2 inhibition
      on ERK-MAPK signaling and the effect of combining MEK (MAPK kinase) and COX-2
      inhibitors in human hepatocellular carcinoma in vitro. COX and ERK expression
      were determined by immunoblot in HepG2 and Hep3B cells. COX-2 and MEK activity
      were determined by prostaglandin E(2) assay and phosphospecific immunoblot,
      respectively. Cell growth was determined by cell proliferation and cell counts.
      Apoptosis was determined by DNA fragmentation enzyme-linked immunosorbent assay
      and flow cytometry. Cell cycle was determined by flow cytometry. HepG2 and Hep3B
      cells do not express COX-1 or COX-2. Correspondingly, basal and agonist
      (arachidonic acid, lipopolysaccharide)-stimulated COX-2 activity is undetectable.
      Treatment of HepG2 and Hep3B cells with NS398 resulted in an increase in ERK1/2
      phosphorylation (MEK activity) in a concentration-dependent fashion (NS398, 1 to
      100 micromol/L). Treatment with the COX-2 inhibitor NS398 in the presence of
      U0126 (MEK inhibitor) effectively suppressed ERK1/2 phosphorylation as determined
      by phosphospecific ERK1/2 immunoblot. Total ERK1/2 and COX-2 were unchanged with
      NS398 and U0126 treatments. In HepG2 cells, NS398 (1 to 100 micromol/L) decreased
      apoptosis as determined by DNA fragmentation enzyme-linked immunosorbent assay.
      Relative apoptosis was increased with U0126 alone or in combination with NS398 (9
      to 10 times the control value), eliminating the anti-apoptotic effect of NS398.
      In Hep3B cells, apoptosis was unchanged with NS398 (1 to 50 micromol/L) or U0126
      (1 to 10 micromol/L) alone. The combination of NS398 and U0126 in Hep3B cells
      resulted in a synergistic increase in apoptosis (10 times the control value).
      Relative apoptosis in both cell lines strongly correlated with changes in the
      expression of the antiapoptotic protein Bcl-xL. Cellular growth was assessed by
      colorimetric proliferation assay and cell counts. HepG2 and Hep3B cells had
      concentration-dependent inhibition of cell growth with NS398 or U0126 treatment
      alone. The combination of NS398 and U0126 resulted in complementary inhibitory
      effects on growth. Growth inhibitory effects in HepG2 and Hep3B cells with
      combination treatment appear to be, in part, secondary to the induction of
      G(0)/G(1) and G(2)/M cell cycle arrest, respectively, as determined by flow
      cytometry. Despite differential signaling in HepG2 and Hep3B cells, the sum
      effect of combining the COX-2 inhibitor NS398 and the MEK inhibitor U0126 results
      in enhanced antitumor actions. This novel combination may be useful for in vivo
      studies of hepatocellular carcinoma.

PMID- 14675713
TI  - Impact of steatosis on perioperative outcome following hepatic resection.
AB  - Fatty liver disease may interfere with liver regeneration and is postulated to
      result in an adverse outcome for patients subjected to partial hepatectomy. This
      study examines the impact of steatosis on outcome following hepatic resection for
      neoplasms. All patients with fatty livers (n=325) who underwent hepatectomy
      between December 1991 and September 2001 were identified from a prospective
      database. Slides were reviewed and steatosis was quantified as follows: <30%
      (mild) and > or =30% (marked). Patient data were gathered and compared with
      results in 160 control patients with normal livers; subjects were matched for
      age, comorbidity, and extent of liver resection. There were 223 patients with
      mild and 102 with marked steatosis. Those with steatosis were more likely to be
      men (59% marked vs. 55% mild vs. 43% control; P=0.01) with a higher body mass
      index (29.7+/-5.5 marked vs. 28.2+/-5.5 mild vs. 26.0+/-5.4 control; P<0.01), and
      treated preoperatively with chemotherapy (66% marked vs. 55% mild vs. 38%
      control; P<0.01). Total (62%, 48%, and 35%; P<0.01) and infective (43%, 24%, and
      14%; P<0.01) complications correlated with the degree of steatosis. No difference
      was observed in complications requiring major medical intervention,
      hospitalization, or admission to the intensive care unit between groups. On
      multivariate analysis, steatosis was an independent predictor of complications
      (P<0.01, risk ratio=3.04, 95% confidence interval=1.7 to 5.54). There was a
      nonsignificant trend toward higher 60-day mortality in patients with marked
      steatosis who had lobe or more resections (9.4% marked vs. 5.0% mild vs. 5.0%
      control; P=0.30). Marked steatosis is an independent predictor of complications
      following hepatic resection but does not have a significant impact on 60-day
      mortality. Steatosis alone should not preclude aggressive hepatic resection for
      neoplasms when indicated; however, patients with marked steatosis undergoing
      large resections should still be approached with due caution.

PMID- 14675714
TI  - Metabolic acidosis stimulates intestinal glutamine absorption.
AB  - Glutamine is an essential nutrient for cell integrity during acidotic states such
      as shock, but the effect of extracellular pH on intestinal mucosal cell glutamine
      uptake is poorly understood. The purpose of this in vitro study was to
      investigate the intracellular signaling pathways involved in controlling
      intestinal glutamine transport during acidosis. Lowering the pH in the cell
      culture medium resulted in an increase in glutamine transport activity in a time-
      and pH-dependent fashion. Chronic acidosis (pH 6.6 for 48 hours) resulted in a
      twofold increase in glutamine transport activity (1.63+/-0.25 nmole/mg
      protein/minute in acidosis vs. 0.78+/-0.11 nmole/mg protein/minute in control)
      and a threefold increase in glutamine transport gene ATB(0) messenger RNA levels.
      This acidosis-induced increase in glutamine transport activity was due to a
      stimulation of transporter maximal transport capacity (V(max) 13.6+/-0.73
      nmole/mg protein/minute in acidosis vs. 6.3+/-0.46 nmole/mg protein/minute in
      control) rather than a change in transporter affinity (K(m)=0.23+/-0.02 mmol/L
      glutamine in acidosis vs. 0.19+/-0.02 mmol/L glutamine in control). This acidosis
      stimulated glutamine transport activity was blocked by actinomycin-D or
      cycloheximide. Cellular mitogen-activated protein kinase (MAPK) MEK1/2 and p42/44
      levels were elevated in acidotic cells, and the acidosis-induced glutamine
      transport activity was blocked by the MAPK MEK 1 inhibitor PD 98059. Acidosis
      stimulates glutamine transport in Caco-2 cells via signaling pathways that lead
      to transcription of the glutamine transporter gene and translation of functional
      transporters. Mitogen-activated protein kinases are key intracellular regulators
      involved in this signal transduction cascade. An increased availability of
      glutamine to cells subjected to redox stress may help in maintaining cellular
      integrity.

PMID- 14675715
TI  - Convergence of the thyroid hormone and gut-enriched Kruppel-like factor pathways
      in the context of enterocyte differentiation.
AB  - The gut-enriched Kruppel-like factor (KLF4) and the ligand-bound thyroid hormone
      receptor (TR) have each been shown to play a critical role in mammalian gut
      development and differentiation. We investigated an interrelationship between
      these two presumably independent pathways using the differentiation marker gene,
      intestinal alkaline phosphatase (IAP). Transient transfections were performed in
      Cos-7 cells using luciferase reporter plasmids containing a 2.5 kb segment of the
      proximal human IAP 5' regulatory region, as well as multiple deletions. Cells
      were cotransfected with TR and/or KLF4 expression vectors and treated+/-100
      nmol/L thyroid hormone (T3). IAP reporter gene transactivation was increased
      independently by KLF4 (ninefold) and ligand-bound TR beta 1 (sevenfold). Cells
      cotransfected with KLF4 and TR beta 1 in the presence of T3 showed synergistic
      activation (70-fold). A similar pattern was seen with the other T3 receptor
      isoform, TR alpha 1. The synergistic effect was lost with deletions of the T3 and
      KLF4 response elements in the IAP promoter and was completely or partially
      abolished in the case of mutant KLF4 expression vectors. The thyroid hormone
      receptor complex and KLF4 synergistically activate the enterocyte differentiation
      marker gene IAP, suggesting a previously unrecognized interrelationship between
      these two transcription factor pathways.

PMID- 14675716
TI  - Hepatocyte growth factor ameliorates inflammatory bowel disease in a rat model.
AB  - This study was designed to investigate the benefits of administration of
      hepatocyte growth factor in a rat model of inflammatory bowel disease.
      Transfection of the HLA-B27 gene into Fisher rats induces a phenotype similar to
      inflammatory bowel disease. Fisher rats and HLA-B27 rats were divided into six
      groups: (1) Fisher, intravenous saline; (2) HLA-B27, intravenous saline; (3) HLA
      B27, intravenous hepatocyte growth factor; (4) Fisher, luminal saline; (5) HLA
      B27, luminal saline; and (6) HLA-B27, luminal hepatocyte growth factor. Rats
      received a 14-day infusion through an osmotic pump attached to a catheter
      positioned in either the jugular vein or the terminal ileum. Rats were evaluated
      for stool character, and gross and microscopic bowel inflammation. Statistics
      were analyzed using analysis of variance or the Kruskal-Wallis nonparametric
      test. A value of P<0.05 was significant. Compared to untreated HLA-B27 rats,
      intravenous administration of hepatocyte growth factor decreased diarrhea by 41%
      and microscopic inflammation by 54% (P<0.05). Luminal hepatocyte growth factor
      exposure decreased total bowel lesions by 53% and microscopic inflammation by 40%
      compared to untreated HLA-B27 rats (P<0.05), but it did not have an effect on
      diarrhea. Administration of hepatocyte growth factor ameliorates many of the
      features of bowel disease in this rat model and theoretically could have
      therapeutic applications in the management of inflammatory bowel disease in
      humans.

PMID- 14675717
TI  - Short bowel syndrome and Crohn's disease.
AB  - Patients with Crohn's disease are at high risk for recurrent disease and often
      undergo multiple operations. Our aims were to evaluate surgical management and
      outcome of patients with Crohn's disease who develop short bowel syndrome (SBS)
      and to identify factors leading to this complication. We reviewed the records of
      170 adult patients with SBS evaluated over a 20-year period. Thirty (18%) had
      Crohn's disease. SBS was defined as an intestinal remnant less than 180 cm with
      associated malabsorption. There were 20 women and 10 men ranging in age from 18
      to 62 years. Eighteen (60%) presented initially with ileocolonic disease, seven
      (23%) with colonic disease, and five (17%) with small intestinal disease. The
      interval from initial diagnosis to development of SBS ranged from 2 to 32 years,
      with 21 patients (71%) having an interval greater than 15 years. The number of
      resections leading to SBS varied from 2 to 12 with 24 patients (80%) having four
      or fewer resections. Nineteen patients (63%) had an ostomy. Small intestinal
      remnant length was less than 60 cm in 10 patients, 60 to 120 cm in six patients,
      and greater than 120 cm in 14 patients. Only one patient underwent
      stricturoplasty before developing SBS. Five patients were initially diagnosed as
      having ulcerative colitis and underwent a pouch procedure, which was subsequently
      resected. Twenty patients (67%) required parenteral nutrition. Three patients
      have undergone reversed intestinal segment to slow intestinal transit. Two
      patients underwent intestinal transplantation. Two patients have died: one from
      parenteral nutrition-related liver failure and the other after intestinal
      transplantation. Crohn's disease remains a common cause of SBS. Aggressive
      resectional therapy, surgical complications, and errors in initial diagnosis
      contribute to development of SBS in these patients. Selected patients are
      candidates for surgical therapy for SBS.

PMID- 14675718
TI  - Postoperative colonic motility in patients following laparoscopic-assisted and
      open sigmoid colectomy.
AB  - Clinical reports on laparoscopic-assisted sigmoid colectomy (LASC) suggest that
      the period of postoperative inhibition of gastrointestinal motility is shortened
      as compared to open sigmoid colectomy (OSC). We aimed to specifically investigate
      whether colonic motility increases more rapidly following LASC compared to OSC.
      LASC was performed in 11 patients and OSC in nine patients for recurrent
      diverticulitis or carcinoma. During surgery a manometry catheter was inserted
      into the colon via the anus, and the tip was placed in the splenic flexure.
      Continuous manometric recordings were performed from the day of surgery until
      postoperative day 3 with a four-channel microtransducer manometry system combined
      with a portable data logger. The postoperative colonic motility index was 101+/
      18, 199+/-30, and 163+/-27 mm Hg/min on days 1, 2, and 3 after LASC,
      respectively, which was increased compared to indexes of 53+/-15, 71+/-18, and
      76+/-23 following OSC (mean+/-standard error of the mean; P<0.05). The amplitude
      but not the frequency of contractions was higher following LASC compared to OSC.
      Following LASC, patients requested a similar amount of pain medication but
      resumed oral food more rapidly on postoperative days 2 and 3 (P<0.05), and they
      were discharged from the hospital earlier (P<0.05). Colonic motility in
      particular and the patient's condition in general seem to improve more rapidly
      following LASC compared to the open procedure.

PMID- 14675719
TI  - Perioperative complications in patients undergoing major liver resection with or
      without neoadjuvant chemotherapy.
AB  - Systemic chemotherapy is used increasingly prior to resection of hepatic
      colorectal metastases. Previous reports have indicated an increased risk of
      perioperative complications associated with the use of systemic chemotherapy
      prior to resection. The purpose of this study was to investigate perioperative
      complications in patients receiving neoadjuvant systemic chemotherapy consisting
      of 5-fluorouracil (5-FU) and leucovorin (LV) with or without CPT-11 within 6
      months of major liver resection. A retrospective review of 108 patients
      undergoing major liver resection for colorectal metastases with curative intent
      from 1997 to 2002 was performed. Patient and tumor characteristics, perioperative
      parameters, and morbidity and mortality were measured. Forty-seven patients (44%)
      received no chemotherapy, 27 patients (25%) received systemic 5-FU/LV, and 34
      (31%) received systemic 5-FU/LV/CPT-11. A significantly higher number of patients
      in the group treated with preoperative 5-FU/LV plus CPT-11 had multiple tumors.
      Patients in this group also tended to have smaller tumors, fewer complications,
      and a higher R0 margin resection rate, but these findings were not statistically
      significant. Median blood loss and length of hospital stay were also not
      significantly different. There were no perioperative deaths. We conclude that the
      use of fluoropyrimidine-based chemotherapy and CPT-11 prior to major liver
      resection is not associated with increased morbidity or mortality. It may
      therefore provide a better therapeutic option, particularly in patients with
      multiple colorectal metastases.

PMID- 14675720
TI  - Efficacy of venous reconstruction in patients with adenocarcinoma of the
      pancreatic head.
AB  - Pancreaticoduodenectomy is often avoided in patients with portal or superior
      mesenteric venous involvement due to the perception that venous resection is
      complex, morbid, and carries a poor long-term survival. Our recent experience
      using state-of-the-art imaging and strict resection criteria show that venous
      reconstruction increases operative time, transfusion requirements, intensive care
      unit stay, and total hospital length of stay, but has no significant impact on
      operative morbidity rates, mortality rates, or the incidence of positive
      histologic margins. Kalpan-Meier life table analysis shows similar survival
      curves when compared to a contemporary cohort of patients who do not undergo
      venous reconstruction.

PMID- 14675722
TI  - How old is old?

PMID- 14675721
TI  - Influence of mild obesity on outcome of simultaneous pancreas and kidney
      transplantation.
AB  - The influence of body mass index (BMI) on outcome of simultaneous pancreas-kidney
      transplantation (SPK) has not been well described. We retrospectively reviewed 88
      consecutive primary SPKs performed at our institution between March 15, 1995 and
      August 28, 2001. All patients received antibody induction and maintenance
      immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. Systemic
      enteric implantation was performed in all patients. Primary end points were
      patient, pancreas, and kidney survival. Secondary end points were rates of
      anastomotic leakage, pancreas thrombosis, major infection, rejection, repeat
      laparotomy, and length of hospital stay. Values are shown as mean+/-standard
      deviation, range, or percentage. Fifty-two patients (59.1%) were nonobese with a
      BMI < or =24.9 (mean 21.7+/-2.2, range 15.4 to 24.9). Thirty-six patients were
      mild to moderately obese with a BMI > or =25 (mean 27.7+/-2.2, range 25 to 35.1).
      Distribution of recipient age, sex, and ethnicity was similar between groups.
      Kidney and pancreas preservation times were similar between nonobese and obese
      patients. One-, three-, and five-year actuarial patient (nonobese: 95%, 95%, 95%
      vs. obese: 95%, 95%, 89%), kidney graft (nonobese: 91%, 91%, 87% vs. obese: 97%,
      91%, 85%), and pancreas graft (nonobese: 78%, 78%, 73% vs. obese: 70%, 62%, 62%)
      survival were comparable between nonobese and obese (P=NS). The mean rates of
      pancreas thrombosis, major infection, pancreas rejection, kidney rejection,
      relaparotomy, and length of hospital stay were similar in the two groups. The
      overall duodenojejunal anastomotic leakage rate was 8%. Obese patients had a 17%
      incidence of leakage (6 of 36) compared to a 2% incidence of leakage in nonobese
      patients (P=0.012). Six of seven leaks occurred in obese patients. Mean BMI in
      the seven patients with a leak (27+/-1.9) was significantly higher than in
      patients who did not develop a leak (24+/-3.7; P=0.05). Although obesity had no
      effect on patient or graft survival, it was associated with a significantly
      higher leakage rate. There should therefore be a higher degree of suspicion for
      the presence of duodenojejunal anastomotic leaks in obese SPK recipients.

PMID- 14675723
TI  - The need for multiple time points in aging studies.

PMID- 14675724
TI  - Age-related myelin breakdown: a developmental model of cognitive decline and
      Alzheimer's disease.
AB  - A hypothetical model of Alzheimer's disease (AD) as a uniquely human brain
      disorder rooted in its exceptional process of myelination is presented. Cortical
      regions with the most protracted development are most vulnerable to AD pathology,
      and this protracted development is driven by oligodendrocytes, which continue to
      differentiate into myelin producing cells late into the fifth decade of life. The
      unique metabolic demands of producing and maintaining their vast myelin sheaths
      and synthesizing the brain's cholesterol supply make oligodendrocytes especially
      susceptible to a variety of insults. Their vulnerability increases with
      increasing age at differentiation as later-differentiating cells myelinate
      increasing numbers of axonal segments. These vulnerable late-differentiating
      cells drive the protracted process of intracortical myelination and by increasing
      local cholesterol and iron levels, progressively increase the toxicity of the
      intracortical environment forming the basis for the age risk factor for AD. At
      older ages, the roughly bilaterally symmetrical continuum of oligodendrocyte
      vulnerability manifests as a progressive pattern of myelin breakdown that
      recapitulates the developmental process of myelination in reverse. The ensuing
      homeostatic responses to myelin breakdown further increase intracortical toxicity
      and results in the relentless progression and non-random anatomical distribution
      of AD lesions that eventually cause neuronal dysfunction and degeneration. This
      process causes a slowly progressive disruption of neural impulse transmission
      that degrades the temporal synchrony of widely distributed neural networks
      underlying normal brain function. The resulting network "disconnections" first
      impact functions that are most dependent on large-scale synchronization including
      higher cognitive functions and formation of new memories. Multiple genetic and
      environmental risk factors (e.g. amyloid beta-peptide and free radical toxicity,
      head trauma, anoxia, cholesterol levels, etc.) can contribute to the cognitive
      deficits observed in aging and AD through their impact on the life-long
      trajectory of myelin development and breakdown. This development-to-degeneration
      model is testable through imaging and post mortem methods and highlights the
      vital role of myelin in impulse transmission and synchronous brain function. The
      model offers a framework that explains the anatomical distribution and
      progressive course of AD pathology, some of the failures of promising therapeutic
      interventions, and suggests further testable hypotheses as well as novel
      approaches for intervention efforts.

PMID- 14675725
TI  - Poor and protracted myelination as a contributory factor to neurodegenerative
      disorders.

PMID- 14675726
TI  - The possible role of myelin destruction as a precipitating event in Alzheimer's
      disease.

PMID- 14675727
TI  - Oligodendrocyte degeneration in AD.

PMID- 14675728
TI  - White matter mapping is needed.

PMID- 14675729
TI  - A disturbance of late myelination as a trigger for Alzheimer's disease.

PMID- 14675730
TI  - Myelin breakdown in Alzheimer's disease: a commentary.

PMID- 14675732
TI  - Regional NAD(P)H:quinone oxidoreductase activity in Alzheimer's disease.
AB  - Converging evidence supports the role of oxidative stress in the pathology of
      Alzheimer's disease (AD). This notion is further supported by recent findings of
      increased NAD(P)H:quinone oxidodreductase (NQO1) activity, a potent antioxidant
      system, in association with hippocampal AD pathology. If increased NQO1 activity
      is truly related to the AD process, however, we would expect to see regional co
      localization of NQO1 activity with AD pathology throughout affected brain regions
      and the absence of NQO1 activity in regions unaffected by AD. We examined this
      hypothesis by measuring NQO1 enzymatic activity and NQO1 immunohistochemical
      staining in regions commonly affected by the AD process such as frontal cortex
      and compared this to regions generally unaffected by the AD process such as
      occipital cortex, cerebellum, and substantia nigra for a group of AD patients and
      controls. The ratio of frontal to cerebellar NQO1 enzymatic activity was
      significantly increased in patients with AD (2.07 +/- 1.90) versus controls (0.60
      +/- 0.31; P < 0.03). Moreover, regional immunohistochemical staining revealed
      specific localization of NQO1 staining to astrocytes and neurites surrounding
      senile plaques. The extent of immunohistochemical staining also closely
      correlated with the extent of local AD pathology across the various brain regions
      examined. Neuronal NQO1 staining seen in frontal cortex of AD patients was absent
      in frontal cortex of controls, but was found to the same extent in neurons of the
      substantia nigra of both AD patients and controls. We conclude that NQO1 activity
      co-localizes closely with AD pathology supporting a presumed role as an
      antioxidant system upregulated in response to the oxidative stress of the AD
      process. The antioxidant role for NQO1 is further supported by finding increased
      neuronal NQO1 activity in substantia nigra neurons of both AD patients and
      controls as this neuronal population is known to be under constant oxidative
      stress. While requiring further study, these findings, in conjunction with
      previous work, suggest that increased NQO1 activity may be neuroprotective, may
      offer novel insights into the pathophysiology of AD and may also provide possible
      avenues for future treatment.

PMID- 14675733
TI  - Somatic mitochondrial DNA mutations in cortex and substantia nigra in aging and
      Parkinson's disease.
AB  - Oxidative damage to mitochondrial DNA (mtDNA) increases with age in the brain and
      can induce G:C to T:A and T:A to G:C point mutations. Though rare at any
      particular site, multiple somatic mtDNA mutations induced by oxidative damage or
      by other mechanisms may accumulate with age in the brain and thus could play a
      role in aging and neurodegenerative diseases. However, no prior study has
      quantified the total burden of mtDNA point mutation subtypes in the brain. Using
      a highly sensitive cloning and sequencing strategy, we find that the aggregate
      levels of G:C to T:A and T:A to G:C transversions and of all point mutations
      increase with age in the frontal cortex (FCtx). In the substantia nigra (SN), the
      aggregate levels of point mutations in young controls are similar to the levels
      in the SN or FCtx of elderly subjects. Extrapolation from our data suggests an
      average of 2.7 (FCtx) to 3.2 (SN) somatic point mutations per mitochondrial
      genome in elderly subjects. There were no significant differences between
      Parkinson's disease (PD) patients and age-matched controls in somatic mutation
      levels. These results indicate that individually rare mtDNA point mutations reach
      a high aggregate burden in FCtx and SN of elderly subjects.

PMID- 14675734
TI  - Abeta-mediated activation of the apoptotic cascade in cultured cortical neurones:
      a role for cathepsin-L.
AB  - Deposition of beta-amyloid protein in the brain is a neuropathological hallmark
      of Alzheimer's disease. An additional feature of this disease is an upregulation
      of the lysosomal system, however, the role of lysosomal proteins in the
      pathogenesis of this neurodegenerative condition is unclear. In this study, we
      demonstrate that Abeta increases activity of the lysosomal protease, cathepsin-L,
      and promotes a transient increase in cytosolic expression of cathepsin-L in
      cultured cortical neurones. The increase in cathepsin-L activity and
      concentration in the cytosol is evident 6 h following beta-amyloid treatment. The
      proclivity of beta-amyloid to induce apoptotic changes, such as activation of
      caspase-3, cleavage of the DNA repair enzyme, poly-ADP ribose polymerase, and DNA
      fragmentation, were prevented by the selective cathepsin-L inhibitor Z-FF-FMK. In
      contrast, beta-amyloid had no effect on expression levels or cellular
      distribution of cathepsin-D and the cathepsin-D inhibitor peptide failed to
      protect cortical neurones from beta-amyloid-induced apoptosis. Thus, the results
      from this study demonstrate that beta-amyloid impacts on cathepsin-L as an
      upstream event in the neurodegenerative process and this result highlights the
      potential role of lysosomal components in the pathogenesis of Alzheimer's
      disease.

PMID- 14675735
TI  - Insulin inhibits amyloid beta-induced cell death in cultured human brain
      pericytes.
AB  - Amyloid-beta (Abeta) deposition in the cerebral arterial and capillary walls is
      one of the characteristics of Alzheimer's disease and hereditary cerebral
      hemorrhage with amyloidosis-Dutch type. In vitro, Abeta1-40, carrying the "Dutch"
      mutation (DAbeta1-40), induced reproducible degeneration of cultured human brain
      pericytes (HBP), by forming fibrils at the cell surface. Thus, this culture
      system provides an useful model to study the vascular pathology seen in
      Alzheimer's disease. In this study, we used this model to investigate the effects
      of insulin on Abeta-induced degeneration of HBP, as it has been mentioned
      previously that insulin is able to protect neurons against Abeta-induced cell
      death. The toxic effect of DAbeta1-40 on HBP was inhibited by insulin in a dose
      dependent matter. Insulin interacted with Abeta and inhibited fibril formation of
      Abeta in a cell-free assay, as well as at the cell surface of HBP. Our data
      indicate that the formation of a fibril network is essential for Abeta-induced
      cell death in HBP. Additionally, insulin may be involved in the regulation of
      Abeta fibrillization in AD.

PMID- 14675736
TI  - Cytochrome c oxidase is decreased in Alzheimer's disease platelets.
AB  - Cytochrome c oxidase (COX) activity reportedly is reduced in Alzheimer's disease
      (AD) brain and platelets. The reasons for the defect in either tissue are
      unknown, but its presence in a non-degenerating tissue suggests it is not simply
      a consequence of neurodegeneration. We now offer confirmation of the AD platelet
      COX defect. Compared to age-matched controls, in mitochondria isolated from AD
      platelets there was a 15% decrease in COX activity despite the fact that COX
      subunits were present at normal levels. Platelet ATP levels were diminished in AD
      (from 11.33 +/- 0.52 to 9.11 +/- 0.72 nmol/mg), while reactive oxygen species
      (ROS) were increased (from 97.03 +/- 25.9 to 338.3 +/- 100 K/mg). Platelet
      membrane fluidity, Vitamin E, and cholesterol content were similar between
      groups. We conclude that COX catalytic activity is indeed diminished in AD
      platelet mitochondria, does not result from altered membrane fluidity, and is
      associated with ROS overproduction and ATP under-production.

PMID- 14675737
TI  - Circadian rhythms in SAMP8: a longitudinal study of the effects of age and
      experience.
AB  - Age-related effects on circadian rhythms include reductions of rhythm amplitude,
      alterations in re-entrainment, and increased fragmentation. Currently, the
      pattern of these changes across an individuals' lifespan is unknown. The present
      study used a cross-sequential experimental design to determine the pattern of
      circadian rhythm changes, identify predictors of later circadian rhythm
      disruption, and assess the effect of prior run-wheel experience on circadian
      rhythms. Run-wheel activity was assessed in senescence-accelerated mice (SAMP8)
      at 2, 7, and 12 months of age. Age-related changes included decrease of run-wheel
      activity, decrease in circadian rhythm amplitude, increase in proportion of light
      activity, and increase in split activity rhythms. Proportion of light activity at
      2 months was a good predictor of circadian rhythm disruption at 7 months. Run
      wheel experience increased overall activity and decreased proportion of light
      activity, but did not alter rhythm amplitude or period. These results demonstrate
      that aging produces several patterns of circadian rhythm changes, describe
      predictive measures of future rhythm disruptions, and suggest an intervention to
      reduce circadian rhythm disruptions.

PMID- 14675738
TI  - Aging increases amyloid beta-peptide-induced 8-iso-prostaglandin F2alpha release
      from rat brain.
AB  - In order to investigate whether amyloid beta-peptide-induced oxidative damage in
      the brain could be related to aging, we studied the release of 8-iso
      prostaglandin (PG)F2alpha, a stable marker of cellular oxidative stress, in brain
      synaptosomes from Wistar rats of different ages (3, 6, 12, 18 months old), both
      basally and after amyloid beta-peptide (1-40) perfusion. We found that basal
      release of 8-iso-PGF2alpha was not significantly different among all age groups
      of rats. Either phospholipase A2 activation induced by calcium ionophore A23187
      (10 nM) or amyloid beta-peptide (5 microM) did not modify isoprostane release,
      when these substances were used alone. In contrast, amyloid beta-peptide (1-5
      microM) preincubation caused a dose-dependent increase of A23187-stimulated 8-iso
      PGF2alpha release in each age group, which was also strikingly correlated to
      aging of rats. Furthermore, ferric ammonium sulfate stimulates isoprostane
      production to levels comparable to those induced by amyloid beta-peptide. In
      conclusion, although 8-iso-PGF2alpha production from rat brain synaptosomes is
      independent from aging in the basal state, aging renders neurons more vulnerable
      to amyloid beta-peptide-induced oxidative toxicity.

PMID- 14675739
TI  - Depressed contractile function and adrenergic responsiveness of cardiac myocytes
      in an experimental model of Parkinson disease, the MPTP-treated mouse.
AB  - Radiotracer and biochemical studies have shown that patients with Parkinson
      disease lack functional sympathetic innervation to the heart. The same
      observation was made in mice treated with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP), an experimental model of Parkinson disease. This study
      examined the mechanical properties, adrenergic receptor level and intracellular
      Ca2+ handling in cardiac myocytes isolated from C57/BL6 mice that received either
      MPTP (30 mg/kg, i.p., twice in 24 h) or vehicle. Mechanical properties were
      evaluated using an IonOptix MyoCam system. Myocytes were electrically stimulated
      at 0.5 Hz. The contractile properties analyzed included peak shortening (PS),
      time-to-PS (TPS), time-to-90% relengthening (TR90), and maximal velocities of
      shortening and relengthen (+/-dL/dt). Intracellular Ca2+ handling was evaluated
      with fura 2. Myocytes from MPTP-treated mice exhibited a depressed PS (85% of
      normal), normal TPS, prolonged TR90 (147% of normal), and reduced +/-dL/dt (both
      79% of normal). These results were correlated with a 67% reduction of beta
      adrenergic receptor expression in myocardial membranes from MPTP-treated mice
      when compared to normal. Myocytes from MPTP-treated mice also exhibited a reduced
      peak of intracellular Ca2+ sequestration and sarcoplasmic reticulum (SR) Ca2+
      load (55 and 38% of normal, respectively). The resting intracellular Ca2+ and
      Ca2+-transient decay were comparable to the values seen in myocytes from
      untreated mice. Myocytes from MPTP-treated and untreated mice were equally
      responsive over a range of stimulation frequencies (0.1, 0.5, 1, 3 and 5 z).
      Response to norepinephrine (1 microM) and isoproterenol (1 microM) was reduced in
      myocytes from MPTP-treated mice. These results demonstrate substantial cardiac
      dysfunctions in this model of experimental Parkinson disease, probably due to
      reduced adrenergic responsiveness and SR Ca2+ load.

PMID- 14675740
TI  - Executive dysfunctions as potential markers of familial vulnerability to bipolar
      disorder and schizophrenia.
AB  - Attentional and executive impairments have been found both in patients with
      schizophrenia and in their unaffected first-degree relatives, suggesting that
      they might be considered as familial vulnerability markers. Several studies have
      shown that the performance of bipolar patients does not significantly differ from
      that of schizophrenic patients, so that executive and attentional deficits might
      not be specific to schizophrenia. In the present study, we aimed to identify
      executive dysfunctions in schizophrenia and bipolar disorder that might be
      vulnerability trait markers specific to one or common to both of these diseases.
      We assessed cognitive performance of euthymic bipolar and schizophrenic patients,
      their unaffected first-degree relatives and a healthy control group, using
      neuropsychological tasks to test different components of executive function: the
      Verbal Fluency Test, the Stroop Word Colour Test, the Wisconsin Card Sorting Test
      and the Trail Making Test. The two groups of patients and their unaffected
      relatives demonstrated disproportionately increased slowness on the Stroop test
      in comparison to the normal healthy group. Patients with schizophrenia performed
      poorly on all the tests in comparison to the normal healthy subjects, while no
      other impairment was observed in the bipolar patients and in the relatives of
      schizophrenic and bipolar patients. Enhanced susceptibility to interference and
      reduced inhibition could be transnosographical markers for a shared familial
      vulnerability common to schizophrenia and bipolar disorders.

PMID- 14675741
TI  - Relationship of good and poor Wisconsin Card Sorting Test performance to illness
      duration in schizophrenia: a cross-sectional analysis.
AB  - The authors investigated whether schizophrenic patients with good and poor
      performance on the Wisconsin Card Sorting Test (WCST) showed cognitive
      modifications related to duration of illness. Of the 154 patients evaluated with
      the WCST, 56 subjects had normal or mildly impaired performance and 98 showed
      impairment on the basis of the number of categories achieved (0-3 categories =
      poor performance). These subsamples were then cross-sectionally divided into
      three subsamples depending on length of illness (< 5 years, 6-10 years, > 10
      years). The inclusion of 69 healthy controls allowed the effect of age to be
      taken into account. The schizophrenic group as a whole and the group of poor
      performers did not show differences in any of the WCST indices related to length
      of illness. Good performers instead showed improvement on the intermediate length
      of-illness group (6-10 years of illness), and then decline in the third one (> 10
      years). Good performers only showed a positive significant correlation between
      age, age at onset, educational level and successful WCST performance. Results for
      the poor performers support the hypothesis of no progressive 'deteriorating'
      course of schizophrenia, while good performers show an unstable pattern of
      cognitive functions. These data support the hypothesis that cognitive deficits
      associated with schizophrenia cannot be considered a unitary trait, but emerge
      along different hypothetical trajectories.

PMID- 14675742
TI  - Clock Drawing Test in patients with schizophrenia.
AB  - Investigations of the usefulness of the Clock Drawing Test (CDT) in schizophrenia
      have focused primarily on institutionalized or elderly patients. The purpose of
      the present study was to compare CDT performance of patients with schizophrenia
      living in the community with that of normal controls. Fifty-three patients with
      schizophrenia were compared with 66 age- and gender-matched normal controls. The
      CDT ('free-drawn', 'pre-drawn' and three 'examiner' conditions) and the Mini
      Mental State Examination (MMSE) were administered to all participants. In
      patients with schizophrenia, symptom severity was assessed with the Positive and
      Negative Syndrome Scale (PANSS). Patients with schizophrenia had significantly
      lower scores on the MMSE and the five CDT conditions than the control group. When
      MMSE scores and level of education were included in the comparisons as
      covariates, the differences between the two groups remained significant. MMSE
      scores of the patients with schizophrenia correlated significantly with four
      clock conditions: 'free-drawn' 'pre-drawn' and two of the 'examiner' conditions
      (11:10 and 8:20). Poorer performance on the CDT correlated with higher scores on
      the PANSS positive symptoms subscale. Qualitative analysis of the clocks that
      were drawn revealed specific errors in the schizophrenia group relating to
      frontal processes: difficulty placing numbers in the correct position, failure to
      indicate the minute targets, displacement of the minute hand from the minute
      number, and failure to draw a longer minute hand. The fact that the CDT is
      sensitive enough to detect the cognitive impairment inherent in schizophrenia, as
      well as being correlated with symptom severity, makes this test useful in roughly
      assessing cognitive state in schizophrenia.

PMID- 14675743
TI  - Neurobiological correlates of diagnosis and underlying traits in patients with
      borderline personality disorder compared with normal controls.
AB  - The purpose of the study was to test the hypothesis that borderline personality
      disorder (BPD) and its underlying traits are associated with abnormalities in
      neurotransmitter systems. Subjects were 30 women with BPD and 22 normal controls,
      assessed using the Diagnostic Interview for Borderlines, revised, the Hamilton
      Depression Scale (HAM-A) and the Hamilton Anxiety Scale (HAM-A), the Diagnostic
      Assessment of Personality Pathology, the Buss-Durkee Guilt-Hostility Inventory,
      the Barratt Impulsivity Scale (BIS), and challenge tests to measure serotonergic,
      cholinergic and noradrenergic activity. Borderline subjects with high HAM-A and
      HAM-D scores showed a faster time to peak in prolactin response to meta
      chlorphenylpiperazine (m-CPP) challenge. Borderline subjects with high BIS scores
      showed prolactin blunting. There were no differences in cortisol response to m
      CPP, or on the cholinergic and noradrenergic challenges. The results suggest that
      impulsive traits in borderline patients are associated with abnormalities in
      serotonergic systems.

PMID- 14675744
TI  - No evidence for an association between serum cholesterol and the course of
      depression and suicidality.
AB  - In a number of previous reports, an association of altered, in most cases lower,
      serum cholesterol levels with depression, suicidal ideation and current or past
      suicidal behavior has been suggested. In this investigation, the course of serum
      cholesterol concentrations was measured in depressed patients during treatment.
      Ninety-two inpatients with a major depressive episode were included. Serum lipid
      concentrations were assessed at admission, after 1 week and after 4 weeks of
      antidepressant treatment. Degrees of depression and suicidality were measured
      with the Hamilton Depression Rating Scale. Although there was a significant
      reduction in depression and suicidality scores, neither a significant change in
      serum cholesterol levels nor a correlation between cholesterol levels and
      clinical improvement was found. Further, there were no significant differences in
      lipid levels between patients with and without a history of attempted suicide. In
      patients who had used a violent method, there was a trend for lower total
      cholesterol levels compared to those who had poisoned themselves. The results of
      this study do not support the hypothesis of an association of serum cholesterol
      with the course of depression and suicidal ideation. Cholesterol levels do not
      appear to be an appropriate biological marker for suicidality during the first 4
      weeks of treatment in patients with a major depressive episode.

PMID- 14675745
TI  - Do monthly or seasonal variations exist in suicides in a high-risk setting?
AB  - An unequal distribution of suicides over months and seasons has been a consistent
      finding in epidemiological surveys on suicide. Jails and prisons are a high-risk
      setting for suicide all over the world. The high prevalence of both outward and
      self-directed violence in prison populations indicates dysfunctional central
      serotonin (5-HT) neurotransmission and, therefore, could account for an unequal
      distribution of suicides over months and seasons due to underlying bioclimatic
      factors. Within a total survey of suicides in the Austrian penitentiary system,
      the weekly, monthly and seasonal distribution of custodial suicides between 1947
      and 1999 was studied. After an explorative comparison of suicide distribution
      over weekdays, months and seasons of the year by chi2-tests, a harmonic Poisson
      regression model was performed to detect seasonality of suicides. No unequal
      distribution of suicides was evident over the 53-year period. A limitation of
      this study was its sample size of 412, a low number compared with population
      based samples, where a spring suicide peak was consistently found. An explanation
      for lacking seasonality could be that bioclimatic factors are less relevant in
      urban, industrialized areas, where jails and prisons usually are located. One of
      the core characteristics of penal institutions is the limited possibility for
      communication and social interaction. This social isolation is independent of
      seasonal changes. If the individual's possibilities for social interactions are
      limited, the influence of seasonal changes in social activities may be less
      relevant. This could explain the absence of seasonal changes in custodial suicide
      incidence.

PMID- 14675746
TI  - Adult psychopathic personality with childhood-onset hyperactivity and conduct
      disorder: a central problem constellation in forensic psychiatry.
AB  - To describe lifetime mental disorders among perpetrators of severe inter-personal
      crimes and to identify the problem domains most closely associated with
      aggression and a history of repeated violent criminality, we used structured
      interviews, clinical assessments, analyses of intellectual functioning, medical
      and social files, and collateral interviews in 100 consecutive subjects of
      pretrial forensic psychiatric investigations. Childhood-onset neuropsychiatric
      disorders [attention-deficit/hyperactivity disorder (AD/HD), learning disability,
      tics and autism spectrum disorders] affected 55% of the subjects and formed
      complex comorbidity patterns with adult personality disorders [including
      psychopathic traits according to the Psychopathy Checklist (PCL-R)], mood
      disorders and substance abuse. The closest psychiatric covariates to high
      Lifetime History of Aggression (LHA) scores and violent recidivism were the PCL-R
      scores and childhood conduct disorder (CD). Behavioral and affective PCL-R
      factors were closely associated with childhood AD/HD, CD, and autistic traits.
      The results support the notion that childhood-onset social and behavioral
      problems form the most relevant psychiatric symptom cluster in relation to
      pervasive adult violent behavior, while late-onset mental disorders are more
      often associated with single acts of violent or sexual aggression.

PMID- 14675747
TI  - Long-term validity of biological markers of psychopathy and criminal recidivism:
      follow-up 6-8 years after forensic psychiatric investigation.
AB  - This study is a follow-up investigation of a forensic psychiatric sub-population
      6-8 years after forensic psychiatric evaluation. The aim was to examine the long
      term validity of biological markers of psychopathy and antisocial behavior over
      time. Data on criminal records were obtained at follow-up from the National
      Council for Crime Prevention. Basic data included findings of psychiatric and
      psychological assessments, as well as values for serum triiodothyronine (T3) and
      free thyroxin (FT4), and platelet monoamine oxidase (MAO) activity, all obtained
      during the forensic psychiatric examination. Criminal recidivists at follow-up
      had higher serum T3 levels than non-recidivists, and much higher values than
      normal controls, while their levels of free T4 were lower. The T3 levels in
      criminal recidivists correlated to psychopathy- and aggression-related
      personality traits as measured by the Karolinska Scale of Personality. In violent
      recidivists, a remarkably high correlation was noted between T3 levels and
      Irritability and Detachment, traits that have previously been linked to the
      dopaminergic system. Stepwise multiple regression analyses confirmed the
      relationships of T3 levels and platelet MAO activity with personality traits in
      criminal recidivists. The predictive validity of biological markers of
      psychopathy, T3 and platelet MAO, measured during forensic psychiatric
      investigation, is stable over time. The results indicate chronic alterations of
      the hypothalamic-pituitary-thyroid axis in this group of subjects.

PMID- 14675748
TI  - Lifetime and 6-month prevalence of DSM-III-R psychiatric disorders in an urban
      community in Japan.
AB  - We conducted a community-based interview survey of a random sample of residents
      aged 20 years or older in an urban community in Japan using the University of
      Michigan Version of the WHO Composite International Diagnostic Interview for
      selected mood and anxiety disorders and alcohol abuse/dependence according to DSM
      III-R. The final sample consisted of 1029 respondents (response rate, 57%). The
      lifetime and 6-month prevalences of selected mood, anxiety and alcohol use
      disorders were low in general. Alcohol abuse/dependence was more prevalent in men
      than in women. Younger respondents had a greater risk of generalized anxiety
      disorder and alcohol dependence. A greater risk of mood, anxiety and alcohol use
      disorders was observed among a recent birth cohort. We confirmed a lower
      prevalence of mood and anxiety disorders and alcohol use disorders in a community
      population in Japan than in Western countries, observations that were similar to
      previous ones in East-Asian countries. The patterns of demographic correlates and
      comorbidity are similar to those of most other countries.

PMID- 14675749
TI  - Academic deterioration prior to first episode schizophrenia in young Singaporean
      males.
AB  - There has been relatively little study of the longitudinal course of cognitive
      functioning before the onset of schizophrenia. We report scores from standardized
      academic examinations at ages 12 and 16 years of 30 male patients with a first
      episode of schizophrenia (FES) and a normal control group balanced for gender,
      age, parental socio-economic class and academic scores at age 12. The FES group
      had greater deterioration in mathematics scores and poorer educational outcome,
      possibly reflecting neurocognitive changes that preceded the onset of
      schizophrenia.

PMID- 14675750
TI  - Prokaryotic origins for the mitochondrial alternative oxidase and plastid
      terminal oxidase nuclear genes.
AB  - The mitochondrial alternative oxidase is a diiron carboxylate quinol oxidase
      (Dox) found in plants and some fungi and protists, but not animals. The plastid
      terminal oxidase is distantly related to alternative oxidase and is most likely
      also a Dox protein. Database searches revealed that the alpha-proteobacterium
      Novosphingobium aromaticivorans and the cyanobacteria Nostoc sp. PCC7120,
      Synechococcus sp. WH8102 and Prochlorococcus marinus subsp. pastoris CCMP1378
      each possess a Dox homolog. Each prokaryotic protein conforms to the current
      structural models of the Dox active site and phylogenetic analyses suggest that
      the eukaryotic Dox genes arose from an ancestral prokaryotic gene.

PMID- 14675752
TI  - Characterization of a gamma-adaptin ear-binding motif in enthoprotin.
AB  - Enthoprotin, a newly identified component of clathrin-coated vesicles, interacts
      with the trans-Golgi network (TGN) clathrin adapters AP-1 and GGA2. Here we
      perform a multi-faceted analysis of the site in enthoprotin that is responsible
      for the binding to the gamma-adaptin ear (gamma-ear) domain of AP-1. Alanine scan
      mutagenesis and nuclear magnetic resonance (NMR) studies reveal the full extent
      of the site as well as critical residues for this interaction. NMR studies of the
      gamma-ear in complex with a synthetic peptide from enthoprotin provide structural
      details of the binding site for TGN accessory proteins within the gamma-ear.

PMID- 14675751
TI  - TIMP-3 inhibits aggrecanase-mediated glycosaminoglycan release from cartilage
      explants stimulated by catabolic factors.
AB  - Aggrecanases are considered to play a key role in the destruction of articular
      cartilage during the progression of arthritis. Here we report that the N-terminal
      inhibitory domain of tissue inhibitor of metalloproteinases 3 (N-TIMP-3), but not
      TIMP-1 or TIMP-2, inhibits glycosaminoglycan release from bovine nasal and
      porcine articular cartilage explants stimulated with interleukin-1alpha or
      retinoic acid in a dose-dependent manner. This inhibition is due to the blocking
      of aggrecanase activity induced by the catabolic factors. Little apoptosis of
      primary porcine chondrocytes is observed at an effective concentration of N-TIMP
      3. These results suggest that TIMP-3 may be a candidate agent for use against
      cartilage degradation.

PMID- 14675753
TI  - Evidence for a subgroup of thioredoxin h that requires GSH/Grx for its reduction.
AB  - Poplar thioredoxin h4 (popTrxh4) and a related CXXS type (popCXXS3) are both
      members of a plant thioredoxin h subgroup. PopTrxh4 exhibits the usual catalytic
      site WCGPC, whereas popCXXS3 harbors the non-typical active site WCMPS.
      Recombinant popTrxh4 and popCXXS3 are not reduced either by Arabidopsis thaliana
      NADPH-dependent thioredoxin reductases (NTR) A and B or by Escherichia coli NTR.
      We report here evidence that a poplar glutaredoxin as well as three E. coli Grxs
      are able to reduce popTrxh4. PopTrxh4 is able to reduce several thioredoxin
      targets as peroxiredoxins or methionine sulfoxide reductases. On the other hand,
      popCXXS3 exhibits an activity in the presence of glutathione and
      hydroxyethyldisulfide. Except for examples of glutathiolation, these are the
      first two examples of a direct interconnection between the thioredoxin and
      glutathione/glutaredoxin systems.

PMID- 14675754
TI  - Introduction of histidine residues into avidin subunit interfaces allows pH
      dependent regulation of quaternary structure and biotin binding.
AB  - In order to turn the subunit association and biotin binding of avidin into pH
      sensitive phenomena, we have replaced individually three amino acid residues in
      avidin (Met96, Val115 and Ile117) with histidines in the 1-3 interface, and in
      combination with a histidine conversion in the 1-2 interface (Trp110). The single
      replacements Met96His and Val115His in the 1-3 interface were found to have a
      clear effect on the quaternary structure of avidin, since subunit associations of
      these mutants became pH-dependent. The histidine replacement in the 1-2 interface
      affected the biotin-binding properties of the mutants, in particular
      reversibility of binding and protein-ligand complex formation were pH-sensitive,
      as measured by IAsys biosensor and fluorescence correlation spectroscopy,
      respectively. The possibility of regulating the quaternary structure and function
      of avidin in a controlled and predictable manner, due to introduced interface
      histidines, will expand even further the range and versatility of the avidin
      biotin technology.

PMID- 14675755
TI  - RALyase; a terminator of elongation function of depurinated ribosomes.
AB  - Plant ribosomal RNA apurinic site specific lyase (RALyase) cleaves the
      phosphodiester bond at the depurinated site produced by ribosome-inactivating
      protein, while the biological role of this enzyme is not clear. As the
      depurinated ribosomes retain weak translation elongation activities, it was
      suggested that RALyase completes the ribosome inactivation. To confirm this
      point, we measured the effects of the phosphodiester cleavage using a fusion of
      wheat RALyase produced with a cell-free protein synthesis system from wheat germ.
      The results indicated that RALyase diminishes the residual elongation activities
      of the depurinated ribosomes.

PMID- 14675756
TI  - Low frequency of T-DNA based activation tagging in Arabidopsis is correlated with
      methylation of CaMV 35S enhancer sequences.
AB  - A powerful system to create gain-of-function mutants in plants is activation
      tagging using T-DNA based vehicles to introduce transcriptional enhancer
      sequences. Large Arabidopsis populations of individual plants carrying a
      quadruple cauliflower mosaic virus (CaMV) 35S enhancer are frequently used for
      mutant screenings, however the frequency of morphological mutants remains very
      low. To clarify this low frequency we analyzed a subset of lines generated by
      this method. The correlation between the number of T-DNA insertion sites, the
      methylation status of the 35S enhancer sequence and 35S enhancer activity was
      determined. All plants containing more than a single T-DNA insertion showed
      methylation of the 35S enhancer and revealed a dramatic decrease in 35S enhancer
      activity. The results support the notion that in a large proportion of the T-DNA
      based activation tagged lines the 35S transcriptional enhancer is silenced due to
      methylation, which is induced by multiple T-DNA integrations.

PMID- 14675757
TI  - Mapping eIF5A binding sites for Dys1 and Lia1: in vivo evidence for regulation of
      eIF5A hypusination.
AB  - The evolutionarily conserved factor eIF5A is the only protein known to undergo
      hypusination, a unique posttranslational modification triggered by deoxyhypusine
      synthase (Dys1). Although eIF5A is essential for cell viability, the function of
      this putative translation initiation factor is still obscure. To identify eIF5A
      binding proteins that could clarify its function, we screened a two-hybrid
      library and identified two eIF-5A partners in S. cerevisiae: Dys1 and the protein
      encoded by the gene YJR070C, named Lia1 (Ligand of eIF5A). The interactions were
      confirmed by GST pulldown. Mapping binding sites for these proteins revealed that
      both eIF5A domains can bind to Dys1, whereas the C-terminal domain is sufficient
      to bind Lia1. We demonstrate for the first time in vivo that the N-terminal alpha
      helix of Dys1 can modulate enzyme activity by inhibiting eIF5A interaction. We
      suggest that this inhibition be abrogated in the cell when hypusinated and
      functional eIF5A is required.

PMID- 14675758
TI  - The mitochondrial genome of the thermal dimorphic fungus Penicillium marneffei is
      more closely related to those of molds than yeasts.
AB  - We report the complete sequence of the mitochondrial genome of Penicillium
      marneffei, the first complete mitochondrial DNA sequence of a thermal dimorphic
      fungus. This 35 kb mitochondrial genome contains the genes encoding ATP synthase
      subunits 6, 8, and 9 (atp6, atp8, and atp9), cytochrome oxidase subunits I, II,
      and III (cox1, cox2, and cox3), apocytochrome b (cob), reduced nicotinamide
      adenine dinucleotide ubiquinone oxireductase subunits (nad1, nad2, nad3, nad4,
      nad4L, nad5, and nad6), ribosomal protein of the small ribosomal subunit (rps),
      28 tRNAs, and small and large ribosomal RNAs. Analysis of gene contents, gene
      orders, and gene sequences revealed that the mitochondrial genome of P. marneffei
      is more closely related to those of molds than yeasts.

PMID- 14675759
TI  - Properties of the co-chaperone protein p23 erroneously attributed to ALG-2
      (apoptosis-linked gene 2).
AB  - A commercial antibody (clone 22) directed against the apoptosis-linked gene 2
      (alg2, pdcd6) encoded protein has been used by several groups. Up-regulated
      expression of the antigen was observed in primary tumours and in metastatic
      tissue and also during rat brain ischemia. Furthermore, antigen down-regulation
      was found in human atherosclerotic plaques. Recently, we found that the clone 22
      antibody does not recognise ALG-2. In the present study the antigen of the clone
      22 antibody was identified as the heat shock protein 90 (HSP90) co-chaperone
      protein p23, identical to the cytosolic prostaglandin E2 synthase, by
      immunoprecipitation followed by tryptic in-gel digests and mass spectrometry of
      the purified peptides. Moreover, the heterogeneous ribonuclear protein A2/B1 was
      found to be a part of the p23 co-immunoprecipitated protein complex.

PMID- 14675760
TI  - GFPs of insertion mutation generated by molecular size-altering block shuffling.
AB  - Insertion and deletion analyses of a protein have been less common than point
      mutation analyses, partly due to the lack in effective methods. This is the case
      with the green fluorescent protein (GFP), which is so widely applied in molecular
      biology and other fields. In this paper we first introduce a systematic approach
      for generating insertion/deletion mutants of GFP. A new technology of Y-ligation
      based block shuffling (YLBS) was successfully applied to produce size-altered
      GFPs, providing insertion-containing GFPs of fluorescence, though no deletion
      type of fluorescence was obtained so far as examined. The analysis of these
      proteins suggested that size alteration (deletion/insertion) is acceptable so far
      as some type of rearrangement in a local structure can accommodate it. This paper
      demonstrates that YLBS can generate insertion and deletion mutant libraries
      systematically, which are beneficial in the study of structure-function
      relationship.

PMID- 14675761
TI  - Orientation-dependent gene expression with Epstein-Barr virus-derived vectors.
AB  - Episomal vectors, described for efficient and regulated expression of
      heterologous proteins in mammalian cells, have the advantage that they persist in
      multiple copies in the cell without integrating into the chromosome. To
      efficiently express heterologous proteins we used such a vector based on elements
      of the Epstein-Barr virus (EBV), namely the sequences coding for Epstein-Barr
      nuclear antigen 1 and the viral origin of replication. Because constitutive
      expression is often deleterious to the cell, we combined the interferon-inducible
      Mx promoter with this EBV-derived vector. This resulted in an efficient and
      strictly regulated expression of the reporter gene chloramphenicol
      acetyltransferase (CAT) and of the neurotransmitter receptor h5-HT(1B), reaching
      levels of 16 ng CAT/mg cytoplasmic protein and 1300 fmol receptor/mg membrane
      protein, respectively. For both proteins, the expression levels were influenced
      by the orientation of the expression cassette. The higher expression in the
      favored orientation did not result from a higher copy number of these episomes.
      Northern analysis revealed a transcriptional read-through from the thymidine
      kinase promoter on the episomal vector, which interfered with the transcription
      of the heterologous gene in the less favored orientation.

PMID- 14675762
TI  - Characterization of human circulating TIG2 as a ligand for the orphan receptor
      ChemR23.
AB  - The orphan receptor ChemR23 is a G-protein coupled receptor (GPCR) with homology
      to neuropeptide and chemoattractant receptors. Tazarotene, a synthetic retinoid
      activating retinoic acid receptor (RAR), up-regulates tazarotene-induced gene-2
      (TIG2). The function and molecular target of this protein are now described. By
      means of reverse pharmacology screening using a peptide library generated from
      human hemofiltrate, we have isolated and identified TIG2 as the natural ligand of
      ChemR23 and report the specific molecular form of the bioactive, circulating
      TIG2, representing the amino-acid residues 21 to 154 of the 163 amino acid
      containing prepropeptide. Based on the expression pattern of ChemR23 and TIG2,
      the physiological role in bone development, immune and inflammatory responses and
      the maintenance of skin is now being investigated.

PMID- 14675763
TI  - A single aquaporin gene encodes a water/glycerol/urea facilitator in Toxoplasma
      gondii with similarity to plant tonoplast intrinsic proteins.
AB  - We describe a single aquaporin gene in Toxoplasma gondii which, surprisingly, has
      only 28% sequence similarity to the aquaglyceroporin of another apicomplexan
      parasite, Plasmodium falciparum. Sequence comparisons showed 47% similarity to
      water-specific plant aquaporins and the conservation of typical pore-forming
      residues. We established that the Toxoplasma aquaporin protein is a bifunctional
      membrane pore with intermediate water and high glycerol permeability.
      Furthermore, we identified hydroxyurea, an antineoplastic agent with inhibitory
      effects on parasite proliferation, as a permeant of this channel.

PMID- 14675764
TI  - Prediction of the structure and function of AstA and AstB, the first two enzymes
      of the arginine succinyltransferase pathway of arginine catabolism.
AB  - Arginine succinyltransferase and succinylarginine dihydrolase catalyze the first
      two steps of arginine catabolism by the arginine succinyltransferase pathway.
      This route is the only major arginine catabolic pathway in Escherichia coli
      including its pathogenic strains O157 and CFT073. We have used fold recognition
      tools and identified novel homologies between each of these two enzymes and
      proteins of known three-dimensional structure: arginine succinyltransferase
      belongs to the acyl-CoA N-acyltransferase superfamily and succinylarginine
      dihydrolase belongs to the amidinotransferase superfamily. These findings shed
      light on the structures, catalytic mechanisms and evolution of diverse enzymes
      involved in arginine catabolism.

PMID- 14675765
TI  - Multiple functions of tail-anchor domains of mitochondrial outer membrane
      proteins.
AB  - Tail-anchored proteins form a distinct class of membrane proteins that have a
      single membrane anchor sequence at their C-terminus, the tail-anchor. Their N
      terminal portion is exposed to the cytosol. We have studied the roles of tail
      anchor domains of proteins residing in the mitochondrial outer membrane. Four
      distinct functions of the tail-anchor domain were identified. First, the domain
      mediates the targeting to mitochondria in a process that probably requires a net
      positive charge at the C-terminally flanking segment. Second, tail-anchor domains
      facilitate the insertion into the mitochondrial outer membrane. Third, the tail
      anchor is responsible for the assembly of the respective protein into functional
      multi-subunit complexes; and fourth, tail-anchor domains can stabilize such
      complexes.

PMID- 14675766
TI  - Thiamine-regulated gene expression of Aspergillus oryzae thiA requires splicing
      of the intron containing a riboswitch-like domain in the 5'-UTR.
AB  - Exogenous thiamine regulates Aspergillus oryzae thiA, which is involved in
      thiamine synthesis. One of the two introns in its 5'-untranslated region (5'-UTR)
      contains motifs (regions A and B) highly conserved among fungal thiamine
      biosynthesis genes. Deletion of either region relieved the repression by thiamine
      and thiamine inhibited intron splicing, suggesting that regions A and B are
      required for efficient splicing. Furthermore, transcript splicing was essential
      for thiA gene expression. These observations suggest a novel gene expression
      regulatory mechanism in filamentous fungi, in which exogenous thiamine controls
      intron splicing to regulate gene expression. Interestingly, regions A and B
      constitute a part of a thiamine pyrophosphate-binding riboswitch-like domain that
      has been quite recently found in the 5'-UTR of thiA.

PMID- 14675767
TI  - Ternary complex formation between DNA-adenovirus core protein VII and TAF
      Ibeta/SET, an acidic molecular chaperone.
AB  - The adenovirus (Ad) genome complexed with viral core proteins designated Ad core
      is the template for transcription of early genes and the first round of
      replication in Ad-infected cells. A cellular protein designated template
      activating factor-I (TAF-I) is found to be involved in remodeling of the Ad core
      in vitro. Here we found that TAF-I interacts with the Ad DNA through core protein
      VII in infected cells in early phases of infection. In vitro binding assays using
      recombinant proteins showed that TAF-I forms ternary complexes with DNA-protein
      VII complexes.

PMID- 14675768
TI  - Expression of hepatitis C virus non-structural 5A protein in the liver of
      transgenic mice.
AB  - Hepatitis C virus (HCV) is a major etiologic agent for chronic hepatitis
      worldwide often leading to the development of cirrhosis and hepatocellular
      carcinoma. However, the mechanism for development of chronic hepatitis or
      hepatocarcinogenesis by HCV remains unclear. HCV NS5A protein possesses many
      intriguing properties, including sequestration of p53 in the cytoplasm,
      downregulation of p21 protein, activation of STAT3, and inhibition of tumor
      necrosis factor-alpha-mediated apoptosis. Thus, we investigated whether this
      viral protein has oncogenic property in vivo. In the absence of an efficient cell
      culture system for virus growth and a suitable small animal model for HCV
      infection, transgenic FVB mice were generated by targeting the HCV NS5A genomic
      region cloned under the control of a liver-specific apoE promoter or mouse major
      urinary promoter (MUP). The apoE promoter is constitutively expressed in liver,
      on the other hand, the MUP is developmentally regulated and expressed in the
      liver after birth. Reverse transcription polymerase chain reaction and Western
      blot analysis indicated establishment of HCV NS5A transgene expression in several
      lines from both groups of mice. Immunohistochemical studies suggested the
      presence of NS5A in the cytoplasm of hepatocytes. The transgenic animals were
      phenotypically similar to their normal littermates and did not exhibit a major
      histological change within the liver up to 24 months of age. Our results
      suggested HCV NS5A protein is not directly cytopathic or oncogenic in this FVB
      transgenic mouse model, although this viral protein promotes cell growth in
      vitro. These animals will be a valuable model of HCV immunopathology as well as
      for evaluation of siRNA, interferon and other cytokine therapies.

PMID- 14675769
TI  - Identification of a new expanding family of genes characterized by atypical LRR
      domains. Localization of a cluster preferentially expressed in oocyte.
AB  - In the present work, we have used the in silico subtraction methodology to
      identify novel oocyte-specific genes in the mouse. By this way, we have
      identified in silico a new family of genes composed of more than 80 members.
      Sequence analysis showed that these genes belong to the superfamily of leucine
      rich repeat (LRR) proteins. However, LRRs of this family display some variability
      in length and in amino acids composition within the beta-strands region, as more
      leucine residues are substituted by other hydrophobic amino acids as compared to
      canonical LRRs. Interestingly, for nine of these genes, the ESTs were represented
      almost exclusively in mouse egg libraries. Three of them were selected for
      experimental study. By RT-PCR and in situ hybridization, we confirmed their
      specific expression in the mouse oocyte from primary to preovulatory follicles.
      These three genes are localized in a cluster on mouse chromosome 4, in the
      vicinity of another recently discovered oocyte specific gene called oogenesin,
      that we also found to belong to the same family. We thus re-named this latter
      gene 'oogenesin-1', and the three genes identified here were named oogenesin-2, 
      3 and -4.

PMID- 14675770
TI  - Cardio-protective determinants are conserved in aged human myocardium after
      ischemic preconditioning.
AB  - Ischemic preconditioning (IPrec) improves post-ischemic dysfunctions of the
      myocardium along with activation of protein kinase C isozymes including PKCdelta.
      Moreover, expression of cardio-protective determinants can reduce ischemic
      damages. Because IPrec is limited in aged hearts, we assessed in an experimental
      model the impact of aging on PKCdelta and selected protective proteins in the
      preconditioned myocardium from adult (< or =55) and older (> or =70 years)
      humans. Adult myocardium showed PKCdelta up-regulation after IPrec along with
      improved post-ischemic contractility. Although there was no functional benefit,
      PKCdelta increased in older myocardium as well. Subsequent mRNA analyses
      demonstrated that IPrec stabilizes the mRNA expression of protective proteins
      (Hsp70, Bcl-2/-xL, IAPs) in both aging groups. Moreover, older hearts revealed
      increase in post-ischemic Hsp90beta. Our study indicates, that IPrec conserves
      the expression of cardio-protective determinants in aged hearts despite limited
      functional recovery.

PMID- 14675771
TI  - tBid forms a pore in the liposome membrane.
AB  - We investigated the ability of tBid (truncated form of Bid) to bind and
      permeabilize the liposomes (large unilamellar vesicles, LUVs) and release
      fluorescent marker molecules (fluorescein-isothiocyanate-conjugated dextrans,
      FITC-dextrans) of various molecular diameters (FD-20, FD-70, FD-250S) from LUVs.
      Obtained data showed that tBid was more efficient in promoting leakage of FITC
      dextrans from LUVs composed of cardiolipin and dioleoylphosphatidylcholine (DOPC)
      than LUVs made of dioleoylphosphatidic acid or dioleoylphosphatidylglycerol and
      DOPC. The leakage efficiency was reduced with increasing amount of
      dioleoylphosphatidylethanolamine or dielaidoylphosphatidylethanolamine.
      Phospholipid monolayer assay and fluorescence quenching measurements revealed
      that tBid inserted deeply into the hydrophobic acyl chain of acidic
      phospholipids. Taking into account the tBid three-dimensional structure, we
      propose that tBid could penetrate into the hydrophobic core of membrane,
      resulting in the leakage of entrapped content from LUVs via a pore-forming
      mechanism.

PMID- 14675772
TI  - Identification of pollen-expressed pectin methylesterase inhibitors in
      Arabidopsis.
AB  - Pectin methylesterases (PMEs) play an essential role during plant development by
      affecting the mechanical properties of the plant cell wall. Previous work
      indicated that plant PMEs may be subject to post-translational regulation. Here,
      we report the analysis of two proteinaceous inhibitors of PME in Arabidopsis
      thaliana (AtPMEI1 and 2). The functional analysis of recombinant AtPMEI1 and 2
      proteins revealed that both proteins are able to inhibit PME activity from
      flowers and siliques. Quantitative RT-PCR analysis indicated that expression of
      AtPMEI1 and 2 mRNAs is tightly regulated during plant development with highest
      mRNA levels in flowers. Promotor::GUS fusions demonstrated that expression is
      mostly restricted to pollen.

PMID- 14675773
TI  - Comparative functional analysis of the Rac GTPases.
AB  - Small GTPases of the Rho family including Rac, Rho and Cdc42 regulate different
      cellular processes like reorganization of the actin cytoskeleton by acting as
      molecular switches. The three distinct mammalian Rac proteins share very high
      sequence identity but how their specificity is achieved is hitherto unknown. Here
      we show that Rac1 and Rac3 are very closely related concerning their biochemical
      properties, such as effector interaction, nucleotide binding and hydrolysis. In
      contrast, Rac2 displays a slower nucleotide association and is more efficiently
      activated by the Rac-GEF Tiam1. Modeling and normal mode analysis support the
      idea that altered dynamics of Rac2 at the switch I region may be responsible for
      different biochemical properties. These results provide insight into the
      individual functionalities of the Rac isoforms.

PMID- 14675774
TI  - Enhancement of androgen receptor expression induced by (R)-methanandamide in
      prostate LNCaP cells.
AB  - It has been recently shown that cannabinoids may regulate the growth of many cell
      types. In the present work we examined the effect of the anandamide analogue (R)
      methanandamide (MET) on androgen-dependent prostate LNCaP cell growth. We found
      that 0.1 microM MET had a mitogenic effect measured by [(3)H]thymidine
      incorporation into DNA. The effect exerted by MET was blocked by the cannabinoid
      receptor antagonists SR141716 (SR1) and SR144528 (SR2) as well as by the
      phosphoinositide 3-kinase (PI3K) inhibitor LY294002, suggesting an involvement of
      cannabinoid receptors and the PI3K pathway in the mechanism of MET action. MET
      treatment of LNCaP cells also induced an up-regulation of androgen receptor
      expression that was blocked by the two cannabinoid receptor antagonists SR1 and
      SR2. These results show for the first time that cannabinoids may modify androgen
      receptor expression in an androgen-dependent cell line and by this mechanism
      could regulate prostate cell growth.

PMID- 14675775
TI  - Growth hormone induces eNOS expression and nitric oxide release in a cultured
      human endothelial cell line.
AB  - Growth hormone deficiency is linked to cardiovascular disease and particularly
      increased peripheral vascular resistance. Surprisingly, its role in endothelial
      nitric oxide (NO) synthetase (eNOS) regulation and NO release is basically
      unknown. We therefore studied the effects of different doses of somatotropin in
      cultures of a human endothelial cell line (EAhy926). We investigated expression
      and activity of eNOS, as well as other target genes known to be deregulated in
      cardiovascular disease including E-selectin and the lectin-like oxidized low
      density lipoprotein receptor. Treatment of cultured human endothelial cells with
      somatotropin resulted in significant (P<0.05) increases of eNOS gene and protein
      expression, as well as NO release, whereas production of intracellular reactive
      oxygen species was significantly reduced, at the highest somatotropin dose level.
      The enhanced eNOS gene/protein expression and enzyme activity correlate well. Our
      findings are suggestive for a novel role of growth hormone in endothelial
      biology, and particularly NO production.

PMID- 14675776
TI  - Widespread production of novel soluble protein isoforms by alternative splicing
      removal of transmembrane anchoring domains.
AB  - We have investigated the effects of alternative splicing on transcripts encoding
      membrane proteins in 1001 human genes. Out of a total of 464 alternatively
      spliced genes encoding single-pass transmembrane (TM) proteins, in 188 we
      observed a splice form that specifically removed the TM domain, producing a
      soluble protein isoform. For example, in syndecan-4, the new alternative splice
      form closely parallels the proteolytic ectodomain shedding previously shown in
      this protein, and recognized as an important regulatory mechanism of receptor
      function. While many of the soluble isoforms produced by alternative splicing
      have already been validated, most are novel, and in 57 genes showed a
      statistically significant association (P-value<0.01) with a specific tissue.

PMID- 14675777
TI  - Transcription-coupled TA and GC strand asymmetries in the human genome.
AB  - Analysis of the whole set of human genes reveals that most of them present TA and
      GC skews, that these biases are correlated to each other and are specific to gene
      sequences, exhibiting sharp transitions between transcribed and non-transcribed
      regions. The GC asymmetries cannot be explained solely by a model previously
      proposed for (G+T) skew based on transitions measured in a small set of human
      genes. We propose that the GC skew results from additional transcription-coupled
      mutation process that would include transversions. During evolution, both
      processes acting on a large majority of genes in germline cells would have
      produced these transcription-coupled strand asymmetries.

PMID- 14675778
TI  - Gene expression profile linked to p53 status in hepatitis C virus-related
      hepatocellular carcinoma.
AB  - To clarify the role of p53 in 22 hepatitis C virus (HCV)-infected hepatocellular
      carcinomas (HCCs), we compared the gene expression profiles of HCCs with wild
      type p53 (wt-p53) (n=17) and those with mutant-type p53 (mt-p53) (n=5) by
      oligonucleotide microarray analysis. Among 83 p53-related genes identified by a
      supervised learning method, 25 were underexpressed, and 58 were overexpressed in
      mt-p53 HCCs compared with wt-p53 HCCs. With a computer search, we identified
      consensus p53-binding sequences in the 3-kb region upstream of the translation
      initiation site in 59 of the 83 genes, suggesting that the in vivo p53-associated
      transcription system is very complicated. These data will provide additional
      insights into p53-related pathogenesis in HCV-infected HCC.

PMID- 14675779
TI  - PDGF stimulates DNA synthesis in human vascular smooth muscle cells via a novel
      wortmannin-insensitive phosphatidylinositol 3-kinase.
AB  - The class 1(A) phosphatidylinositol 3-kinase enzymes consist of a number of
      heterodimeric complexes of regulatory and catalytic subunits and have been
      implicated in a number of cellular responses. While platelet-derived growth
      factor (PDGF)-induced chemotaxis of human vascular smooth muscle cells (HVSMC) is
      inhibited by both wortmannin and LY294002, DNA synthesis is only inhibited by
      LY294002. Serum-induced DNA synthesis however is inhibited by LY294002,
      wortmannin and rapamycin. Similarly PDGF-induced protein kinase B (PKB)
      activation is inhibited by LY294002 but not by wortmannin or rapamycin. In
      conclusion PDGF-induced DNA synthesis appears to occur through a
      phosphatidylinositol 3-kinase (PI3-K)-dependent, but wortmannin-insensitive,
      PKB/Akt pathway.

PMID- 14675780
TI  - Inhibition of angiotensin converting enzyme (ACE) activity by flavan-3-ols and
      procyanidins.
AB  - It was determined that flavan-3-ols and procyanidins have an inhibitory effect on
      angiotensin I converting enzyme (ACE) activity, and the effect was dependent on
      the number of epicatechin units forming the procyanidin. The inhibition by flavan
      3-ols and procyanidins was competitive with the two substrates assayed: N
      hippuryl-L-histidyl-L-leucine (HHL) and N-[3-(2-furyl)acryloyl]-L
      phenylalanylglycylglycine (FAPGG). Tetramer and hexamer fractions were the more
      potent inhibitors, showing Ki of 5.6 and 4.7 microM, respectively. As ACE is a
      membrane protein, the interaction of flavanols and procyanidins with the enzyme
      could be related to the number of hydroxyl groups on the procyanidins, which
      determine their capacity to be adsorbed on the membrane surface.

PMID- 14675781
TI  - Tetrahydrofolate and 5-methyltetrahydrofolate are folates with high antioxidant
      activity. Identification of the antioxidant pharmacophore.
AB  - The presumed protective effect of folic acid on the pathogenesis of
      cardiovascular, hematological and neurological diseases and cancer has been
      associated with the antioxidant activity of folic acid. Peroxynitrite (PON)
      scavenging activity and inhibition of lipid peroxidation (LPO) of the
      physiological forms of folate and of structurally related compounds were tested.
      It was found that the fully reduced forms of folate, i.e. tetrahydrofolate (THF)
      and 5-methyltetrahydrofolate (5-MTHF), had the most prominent antioxidant
      activity. It appeared that their protection against LPO is less pronounced than
      their PON scavenging activity. The antioxidant activity of these forms of folic
      acid resides in the pterin core, the antioxidant pharmacophore is 4-hydroxy-2,5,6
      triaminopyrimidine. It is suggested that an electron donating effect of the 5
      amino group is of major importance for the antioxidant activity of 4-hydroxy
      2,5,6-triaminopyrimidine. A similar electron donating effect is probably
      important for the antioxidant activity of THF and 5-MTHF.

PMID- 14675782
TI  - Redox characteristics of the tungsten DMSO reductase of Rhodobacter capsulatus.
AB  - The dimethylsulfoxide reductase (DMSOR) from Rhodobacter capsulatus is known to
      retain its three-dimensional structure and enzymatic activity upon substitution
      of molybdenum, the metal that occurs naturally at the active site, by tungsten.
      The redox properties of tungsten-substituted DMSOR (W-DMSOR) have been
      investigated by a dye-mediated reductive titration with the concentration of the
      W(V) state monitored by EPR spectroscopy. At pH 7.0, E(m)(W(VI)/W(V)) is -194 mV
      and E(m)(W(V)/W(IV)) is -134 mV. Each E(m) value of W-DMSOR is significantly
      lower (220 and 334 mV, respectively) than that of the corresponding couple of Mo
      DMSOR. These redox potentials are consistent with the ability of Mo-DMSOR to
      catalyze both the reduction of DMSO to DMS and the back reaction, whereas W-DMSOR
      is very effective in catalyzing the forward reaction, but shows no ability to
      catalyze the oxidation of DMS to DMSO.

PMID- 14675783
TI  - Near-field optical imaging of abasic sites on a single DNA molecule.
AB  - Scanning near-field optical microscopy (SNOM) imaging was performed to allow for
      the direct visualization of damaged sites on individual DNA molecules to a scale
      of a few tens of nanometers. Fluorescence in situ hybridization on extended DNA
      molecules was modified to detect a single abasic site. Abasic sites were
      specifically labelled with a biotinlylated aldehyde-reactive probe and
      fluorochrome-conjugated streptavidin. By optimizing the performance of the SNOM
      technique, we could obtain high contrast near-field optical images that enabled
      high-resolution near-field fluorescence imaging using optical fiber probes with
      small aperture sizes. High-resolution near-field fluorescence imaging
      demonstrated that two abasic sites within a distance of 120 nm are clearly
      obtainable, something which is not possible using conventional fluorescence in
      situ hybridization combined with far-field fluorescence microscopy.

PMID- 14675784
TI  - Function and solution structure of hainantoxin-I, a novel insect sodium channel
      inhibitor from the Chinese bird spider Selenocosmia hainana.
AB  - Hainantoxin-I is a novel peptide toxin, purified from the venom of the Chinese
      bird spider Selenocosmia hainana (=Ornithoctonus hainana). It includes 33 amino
      acid residues with a disulfide linkage of I-IV, II-V and III-VI, assigned by
      partial reduction and sequence analysis. Under two-electrode voltage-clamp
      conditions, hainantoxin-I can block rNa(v)1.2/beta(1) and the insect sodium
      channel para/tipE expressed in Xenopus laevis oocytes with IC(50) values of 68+/
      6 microM and 4.3+/-0.3 microM respectively. The three-dimensional solution
      structure of hainantoxin-I belongs to the inhibitor cystine knot structural
      family determined by two-dimensional (1)H nuclear magnetic resonance techniques.
      Structural comparison of hainantoxin-I with those of other toxins suggests that
      the combination of the charged residues and a vicinal hydrophobic patch should be
      responsible for ligand binding. This is the first report of an insect sodium
      channel blocker from spider venom and it provides useful information for the
      structure-function relationship studies of insect sodium channels.

PMID- 14675785
TI  - Newly identified exons encoding novel variants of p94/calpain 3 are expressed
      ubiquitously and overlap the alpha-glucosidase C gene.
AB  - There are two classes of an intracellular 'modulator protease', calpain:
      ubiquitous and tissue-specific. p94/calpain 3 is an example of the latter,
      predominantly expressed in muscle. A defect in the p94 gene causes muscular
      dystrophy. Here we report that human and mouse p94 genes have a possible novel
      alternative promoter expressing p94 variants in all tissues examined including
      human lens epithelial cells. The possible promoter region and the following novel
      exons overlap the 3' region of the neutral alpha-glucosidase C gene. Unlike p94,
      the novel p94 variants expressed in COS7 cells do not undergo rapid autolysis,
      suggesting basic functions different from p94.

PMID- 14675786
TI  - Differential response of UCP3 to medium versus long chain triacylglycerols;
      manifestation of a functional adaptation.
AB  - We compared UCP3 protein in rat cardiac, glycolytic and oxidative skeletal muscle
      and examined the effect of high-fat medium chain vs. long chain triacylglycerol
      feeding on UCP3 content in these tissues. Cardiac muscle displays the lowest
      basal levels of UCP3 protein. Increasing long chain - but not medium chain -
      fatty acid supply upregulates UCP3 in all muscles. Since plasma non-esterified
      fatty acids and the expression of two peroxisome proliferator-activated receptor
      (PPAR)-responsive genes, were not different between groups, we conclude that the
      differential upregulation of UCP3 is not merely PPAR-mediated. This study
      supports a role of UCP3 in export of non-metabolizable fatty acids.

PMID- 14675787
TI  - The intestinal zonula occludens toxin (ZOT) receptor recognises non-native ZOT
      conformers and localises to the intercellular contacts.
AB  - A preliminary structural analysis of Vibrio cholerae zonula occludens toxin (ZOT)
      was made by equilibrium denaturation and circular dichroism. ZOT is a
      structurally unstable protein in aqueous solution (DeltaG((H2O)) 3.82 kcal/mol),
      the putative intra- and extracellular domains unfold co-operatively, with
      complete denaturation via observed conformational intermediates. Refolding of
      denatured ZOT is not dependent on disulphide bridge formation. Partial refolding
      of a maltose binding protein-ZOT fusion did not prevent its specific binding to
      the ZOT receptor on Caco-2 cells. Immuno-gold labelling showed that the ZOT
      receptor localises to the intercellular contacts between cells in a confluent
      monolayer.

PMID- 14675788
TI  - Climbing out of our boxes: advancing women's health for the twenty-first century.

PMID- 14675789
TI  - Lifetime medical costs for women: cardiovascular disease, diabetes, and stress
      urinary incontinence.
AB  - PURPOSE: To estimate the absolute and relative lifetime medical costs of treating
      women with cardiovascular disease (CVD), diabetes, or stress urinary incontinence
      (SUI). METHODS: Women under 65 years, treated for CVD, diabetes, or SUI, were
      identified using administrative medical claims data from a large employer (n
      >100,000). A case-control methodology was used to estimate the annual medical
      costs of these women. Based on these estimates and published government
      statistics, annual costs for women 65 years and older were calculated. An
      incidence-based methodology with steady-state assumptions was used to project to
      lifetime medical costs. Cost estimates are incremental, measured as the
      difference between costs of patients and their demographically similar controls
      without the condition. They therefore represent the additional costs of treating
      patients with the condition, beyond the average, baseline costs incurred by
      controls without the condition. FINDINGS: The incremental lifetime medical cost
      of treating a woman (in 2002 dollars) with CVD is $423,000, with diabetes is
      $233,000, and with SUI is $58,000 US dollars. Including the baseline medical
      costs of the control, the total lifetime medical costs (i.e., sum of incremental
      and baseline lifetime medical costs) of treating a woman with CVD are 3.4 times
      greater than the costs of a woman without CVD. Similarly, a woman with diabetes
      has total costs on average, 2.5 times greater than the costs of her control,
      whereas a woman with SUI has total lifetime medical costs 1.8 times greater than
      the costs of a similar woman without SUI. CONCLUSIONS: These substantial cost
      estimates suggest the need for further gender-specific research and policies
      addressing the long-term implications of health care financing, treatment, and
      preventive care.

PMID- 14675790
TI  - Presentation, delay, and contraindication to thrombolytic treatment in females
      and males with myocardial infarction.
AB  - BACKGROUND: This study seeks to explore gender-relevant factors of medical
      history, sociodemographics, symptom presentation, and delay on thrombolysis
      administration (or recorded contraindication) in a sample of men and women with
      confirmed myocardial infarction (MI). METHODS: Cross-sectional examination of
      self and nurse-report data collected in the coronary care unit (CCU) from 12
      hospitals across south-central Ontario, Canada. A total of 482 MI patients (347
      males, 135 females; 63% response rate) were recruited. MAIN FINDINGS: There was
      no gender difference in the report of chest pain (chi(2)(1) = 3.78, p =.052), or
      in prehospital delay time (median = 96.5 minutes). Thrombolysis was administered
      in 158 males (68.4%) and 50 females (50.0%) without reported contraindication.
      Females (median = 27 minutes) had a significantly longer interval between
      diagnostic electrocardiogram (ECG) and administration of a thrombolytic than
      males (median = 22, U = 3,056). No contraindication was indicated for not
      administering a thrombolytic (i.e., too late, risk of bleed) in approximately 40%
      of females. In accordance with clinical practice guidelines, thrombolysis was
      more often administered in participants with a shorter time interval between
      symptom onset and hospital arrival. For females, thrombolysis was more often
      administered in younger participants (Kruskal Wallis = 5.88). CONCLUSIONS:
      Reducing gender, age, and socioeconomic disparities in access to thrombolysis
      treatment is imperative. Hospital delays with female cardiac patients may be
      precluding thrombolysis administration.

PMID- 14675791
TI  - Exercising for two: examining pregnant women's second trimester exercise
      intention and behavior using the framework of the theory of planned behavior.
AB  - Research examining the motivational determinants of exercising during pregnancy
      is mostly atheoretical, despite the need for theory-based designs. The study's
      main objective was to prospectively examine women's exercise intention and
      behavior from their second to third pregnancy trimester using the theory of
      planned behavior (TPB). Participants were 89 pregnant women who completed self
      reported measures of their exercise attitude, subjective norm, perceived
      behavioral control, intention, and behavior. Hierarchical regression analyses
      indicated: 1) intention and not perceived behavioral control significantly
      predicted exercise behavior; and 2) attitude was the strongest determinant of
      exercise intention, followed by perceived behavioral control, and subjective
      norm. The study findings provide preliminary support for the TPB as an effective
      framework for examining exercising during pregnancy. Understanding women's
      thoughts, feelings, and beliefs about exercise can assist intervention
      specialists with developing and implementing effective programs promoting
      exercise during pregnancy.

PMID- 14675792
TI  - What are the long-term effects of methylphenidate treatment?

PMID- 14675793
TI  - Methylphenidate-induced plasticity: what should we be looking for?

PMID- 14675794
TI  - Development of human brain functions.
AB  - Aspects of postnatal human brain development are reviewed. The development of
      brain function has commonly been characterized in terms of the unfolding of a
      maturational sequence. In contrast, we argue that postnatal functional brain
      development occurs through a dynamic process of emerging patterns of interactions
      between different brain regions. Some of these processes may also be
      characteristic of perceptual and motor skill learning in adults. Possible
      implications of these views for our understanding of developmental disorders are
      raised.

PMID- 14675795
TI  - Methylphenidate treatment during pre- and periadolescence alters behavioral
      responses to emotional stimuli at adulthood.
AB  - BACKGROUND: Methylphenidate (MPH) is a psychomotor stimulant medication widely
      used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Given
      the extent of prescribed use of MPH, and because MPH interacts with the same
      brain pathways activated by drugs of abuse, most research has focused on
      assessing MPH's potential to alter an individual's risk for adult drug addiction.
      Data examining other potential long-term behavioral consequences of early MPH
      administration are lacking, however. METHODS: We investigated the long-term
      behavioral consequences of chronic administration of MPH (2.0 mg/kg) during pre-
      and periadolescent development in adult rats by assessing their behavioral
      reactivity to a variety of emotional stimuli. RESULTS: The MPH-treated animals
      were significantly less responsive to natural rewards such as sucrose, novelty
      induced activity, and sex compared with vehicle-treated control animals. In
      contrast, MPH-treated animals were significantly more sensitive to stressful
      situations, showed increased anxiety-like behaviors, and had enhanced plasma
      levels of corticosterone. CONCLUSIONS: Chronic exposure to MPH during development
      leads to decreased sensitivity to rewarding stimuli and results in enhanced
      responsivity to aversive situations. These results highlight the need for further
      research to improve understanding of the effects of stimulants on the developing
      nervous system and the potential enduring effects resulting from early-life drug
      exposure.

PMID- 14675796
TI  - Enduring behavioral effects of early exposure to methylphenidate in rats.
AB  - BACKGROUND: Methylphenidate (MPH) is a stimulant prescribed for the treatment of
      attention-deficit/hyperactivity disorder (ADHD). Stimulant drugs can cause
      enduring behavioral adaptations, including altered drug sensitivity, in
      laboratory animals. We examined how early developmental exposure to stimulants
      affects behavior in several rodent models. METHODS: Rats received MPH or cocaine
      during preadolescence (P20-35). Behavioral studies began during adulthood (P60).
      We compared how early exposure to MPH and cocaine affects sensitivity to the
      rewarding and aversive properties of cocaine using place conditioning. We also
      examined the effects of early exposure to MPH on depressive-like signs using the
      forced swim test, and habituation of spontaneous locomotion, within activity
      chambers. RESULTS: In place-conditioning tests, early exposure to MPH or cocaine
      each made moderate doses of cocaine aversive and high doses less rewarding. Early
      MPH exposure also caused depressive-like effects in the forced swim test, and it
      attenuated habituation to the activity chambers. CONCLUSIONS: Early exposure to
      MPH causes behavioral changes in rats that endure into adulthood. Some changes
      (reduced sensitivity to cocaine reward) may be beneficial, whereas others
      (increases in depressive-like signs, reduced habituation) may be detrimental. The
      effects of MPH on cocaine-related behaviors may be a general consequence of early
      stimulant exposure.

PMID- 14675797
TI  - Adolescent exposure to methylphenidate alters the activity of rat midbrain
      dopamine neurons.
AB  - BACKGROUND: Methylphenidate is commonly used to treat children and adolescents
      with attention-deficit/hyperactivity disorder. A health concern is its long-term
      effects with respect to later stimulant exposure. We reported that repeated
      exposure to a low dose of methylphenidate during adolescence increases self
      administration of a low, typically nonreinforcing dose of cocaine in adult rats.
      We also showed that enhanced vulnerability to cocaine is associated with elevated
      impulse and bursting activity of midbrain dopamine neurons in drug-naive adult
      rats and might constitute a substrate critically associated with abuse liability.
      Thus we sought to determine whether repeated exposure to low-dose methylphenidate
      in adolescence alters dopamine neuronal excitability in adulthood. METHODS: After
      3-day and 2-week withdrawal from repeated low-dose adolescent exposure to
      methylphenidate, we used extracellular single-unit recording in chloral hydrate
      anesthetized rats to determine basal firing and bursting activity of midbrain
      dopamine neurons and dopamine autoreceptor sensitivity to the D2-class direct
      receptor agonist quinpirole. RESULTS: Dopamine neuronal impulse activity was
      increased after 3 days and decreased after 2 weeks' withdrawal from
      methylphenidate given in adolescence. No difference between groups was evident
      with respect to autoreceptor sensitivity to quinpirole. CONCLUSIONS: Adolescent
      exposure to methylphenidate induces neuronal changes associated with increased
      addiction liability in rats.

PMID- 14675798
TI  - Inhibitory motor control in children with attention-deficit/hyperactivity
      disorder: event-related potentials in the stop-signal paradigm.
AB  - BACKGROUND: The aim of the study was to investigate the inhibitory control of an
      ongoing motor response and to identify underlying neural deficiencies, manifested
      in event-related potentials, that cause poorer inhibitory performance in children
      with attention-deficit/hyperactivity disorder. METHODS: A stop-signal paradigm
      with a primary visual task and auditory stop signal was used to compare
      performance in 13 children with attention-deficit/hyperactivity disorder and 13
      control children, while event-related potentials were recorded simultaneously.
      RESULTS: Children with attention-deficit/hyperactivity disorder showed poorer
      inhibitory performance through a slower inhibitory process. Inhibitory processing
      of auditory stop signals was marked by a frontal N2 component that was reduced in
      the attention-deficit/hyperactivity disorder group relative to controls. A
      central positive component (P3) was associated with the success of inhibiting a
      response, but there were no group differences in its amplitude or latency.
      CONCLUSIONS: Findings support the hypothesis of deficient inhibitory control in
      children with attention-deficit/hyperactivity disorder. Slower inhibitory
      processing appears to be due to a specific neural deficiency that manifests in
      the processing of the stop signal as attenuated negativity in the N2 latency
      range.

PMID- 14675799
TI  - Proton magnetic resonance spectroscopic imaging of the brain in childhood autism.
AB  - BACKGROUND: Autism is a developmental disorder of unknown neurologic basis. Based
      on prior work, we used proton magnetic resonance spectroscopic imaging ((1)H-
      MRSI) to investigate brain structures, including cingulate and caudate, that we
      hypothesized would reveal metabolic abnormalities in subjects with autism.
      METHODS: In 22 children with autism, 5 to 16 years old, and 20 age-matched
      healthy control subjects, (1)H-MRSI assessed levels of N-acetyl compounds (NAA),
      choline compounds (Cho), and creatine plus phosphocreatine (Cr) at 272 msec echo
      time and 1.5 T. RESULTS: In subjects with autism compared with control subjects,
      Cho was 27.2% lower in left inferior anterior cingulate and 19.1% higher in the
      head of the right caudate nucleus; Cr was 21.1% higher in the head of the right
      caudate nucleus, but lower in the body of the left caudate nucleus (17.9%) and
      right occipital cortex (16.6%). CONCLUSIONS: Results are consistent with altered
      membrane metabolism, altered energetic metabolism, or both in the left anterior
      cingulate gyrus, both caudate nuclei, and right occipital cortex in subjects with
      autism compared with control subjects.

PMID- 14675800
TI  - Differential sex-independent amygdala response to infant crying and laughing in
      parents versus nonparents.
AB  - BACKGROUND: Animal and human studies implicate forebrain neural circuits in
      maternal behavior. Here, we hypothesized that human brain response to emotional
      stimuli relevant for social interactions between infants and adults are modulated
      by sex- and experience-dependent factors. METHODS: We used functional magnetic
      resonance imaging and examined brain response to infant crying and laughing in
      mothers and fathers of young children and in women and men without children.
      RESULTS: Women but not men, independent of their parental status, showed neural
      deactivation in the anterior cingulate cortex, as indexed by decreased blood
      oxygenation level-dependent signal, in response to both infant crying and
      laughing. The response pattern changed fundamentally with parental experience: in
      the amygdala and interconnected limbic regions, parents (independent of sex)
      showed stronger activation from crying, whereas nonparents showed stronger
      activation from laughing. CONCLUSIONS: Our data show sex- and experience
      dependent modulation of brain response to infant vocalizations. Successful
      recognition and evaluation of infant vocalizations can be critical for bonding
      mechanisms and for offspring well-being and survival. Thus, the modulation of
      responses by experience seems to represent an adaptive mechanism that can be
      related to reproductive fitness.

PMID- 14675801
TI  - Association of a genetic marker at the corticotropin-releasing hormone locus with
      behavioral inhibition.
AB  - BACKGROUND: Behavioral inhibition to the unfamiliar (BI), a heritable
      temperamental profile involving an avoidant response to novel situations, may be
      an intermediate phenotype in the development of anxiety disorders. Corticotropin
      releasing hormone (CRH) is a key mediator of the stress response through its
      effects on the hypothalamic-pituitary-adrenal axis and limbic brain systems.
      Transgenic mice overexpressing CRH exhibit BI-like behaviors, implicating this
      gene in the development of the phenotype. METHODS: We genotyped a marker tightly
      linked to the CRH locus in 85 families of children who underwent laboratory-based
      behavioral assessments of BI and performed family-based association analyses.
      RESULTS: We observed an association between an allele of the CRH-linked locus and
      BI (p =.015). Among offspring of parents with panic disorder, this association
      was particularly marked (p =.0009). We further demonstrate linkage disequilibrium
      between this marker and single nucleotide polymorphisms encompassing the CRH
      gene. CONCLUSIONS: These results are consistent with the possibility that
      variants in the CRH gene are associated with anxiety proneness.

PMID- 14675802
TI  - Corticotropin-releasing factor in posttraumatic stress disorder (PTSD) with
      secondary psychotic symptoms, nonpsychotic PTSD, and healthy control subjects.
AB  - BACKGROUND: Recent studies have reported a high comorbidity between posttraumatic
      stress disorder (PTSD) and psychotic symptoms, and it has been hypothesized that
      PTSD with comorbid psychosis is a severe form of PTSD. Few studies have examined
      the neurobiology of PTSD with comorbid psychosis. If PTSD with secondary
      psychotic symptoms (PTSD-SP) is a severe form of PTSD, then it might be expected
      to show more extreme perturbations in the neuroendocrine patterns that
      characterize PTSD. METHODS: Patients with PTSD with secondary psychotic symptoms
      (PTSD-SP), PTSD without psychosis, and healthy comparison subjects were compared
      for differences in cerebrospinal fluid concentrations of corticotropin-releasing
      factor (CRF) and somatotropin-release-inhibiting hormone (SRIF). RESULTS: The
      PTSD-SP subjects had significantly higher mean levels of CRF than either the PTSD
      or control subjects (p <.01). The three groups showed similar SRIF levels.
      CONCLUSIONS: These data implicate abnormalities in the secretion of CRF with the
      production of secondary psychotic symptoms in PTSD. This finding supports the
      validity of PTSD-SP as a PTSD subtype and as a severe form of PTSD.

PMID- 14675803
TI  - Social support and oxytocin interact to suppress cortisol and subjective
      responses to psychosocial stress.
AB  - BACKGROUND: The presence of social support has been associated with decreased
      stress responsiveness. Recent animal studies suggest that the neuropeptide
      oxytocin is implicated both in prosocial behavior and in the central nervous
      control of neuroendocrine responses to stress. This study was designed to
      determine the effects of social support and oxytocin on cortisol, mood, and
      anxiety responses to psychosocial stress in humans. METHODS: In a placebo
      controlled, double-blind study, 37 healthy men were exposed to the Trier Social
      Stress Test. All participants were randomly assigned to receive intranasal
      oxytocin (24 IU) or placebo 50 min before stress, and either social support from
      their best friend during the preparation period or no social support. RESULTS:
      Salivary free cortisol levels were suppressed by social support in response to
      stress. Comparisons of pre- and poststress anxiety levels revealed an anxiolytic
      effect of oxytocin. More importantly, the combination of oxytocin and social
      support exhibited the lowest cortisol concentrations as well as increased
      calmness and decreased anxiety during stress. CONCLUSIONS: Oxytocin seems to
      enhance the buffering effect of social support on stress responsiveness. These
      results concur with data from animal research suggesting an important role of
      oxytocin as an underlying biological mechanism for stress-protective effects of
      positive social interactions.

PMID- 14675804
TI  - Increased medial thalamic choline found in pediatric patients with obsessive
      compulsive disorder versus major depression or healthy control subjects: a
      magnetic resonance spectroscopy study.
AB  - BACKGROUND: Neurobiologic abnormalities in medial thalamus have been implicated
      in the pathogenesis of obsessive-compulsive disorder (OCD). We previously used
      multislice proton magnetic resonance spectroscopic imaging (1-H MRSI) to identify
      localized functional neurochemical marker alterations in choline (Cho) in medial
      but not lateral thalamus in treatment-naive pediatric patients with OCD compared
      with matched control subjects. Altered brain Cho levels have also been implicated
      in the pathogenesis of mood disorders. METHODS: We used 1-H MRSI to study
      absolute Cho concentrations in 18 psychotropic-naive pediatric patients with
      major depressive disorder (MDD) not suffering from OCD, 9-17 years of age, 18
      case-matched healthy control subjects, and 27 nondepressed, psychotropic-naive
      pediatric patients with OCD, 7-16 years of age. RESULTS: Significantly increased
      left and right medial thalamic Cho concentrations were observed in OCD patients
      compared with both healthy control subjects and patients with MDD. Medial
      thalamic Cho concentrations did not differ significantly between patients with
      MDD and control subjects. CONCLUSIONS: These results suggest that localized
      functional neurochemical marker alterations in medial thalamic Cho differentiate
      patients with OCD from healthy control subjects and patients with MDD. Although
      these results must be considered preliminary, further study of the diagnostic
      specificity of Cho as a relevant biomarker in OCD is clearly warranted.

PMID- 14675805
TI  - Elevated brain serotonin transporter availability in patients with obsessive
      compulsive disorder.
AB  - BACKGROUND: A central serotonergic dysfunction is considered to be involved in
      the pathophysiology of obsessive-compulsive disorder (OCD). The aim of this study
      was to investigate the serotonin transporter availability in patients with OCD as
      an in vivo marker of the central serotonergic system. METHODS: Nine unmedicated
      (7 drug-naive) patients with OCD and 10 healthy control subjects were included
      and received single photon emission computed tomography (SPECT) 20.75 +/- 1.51
      hours after injection of a mean 147.20 +/- 6.74 MBq [(123)I]-2beta-carbomethoxy
      3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT). As a measure of brain serotonin
      transporter availability, a ratio of specific-to-nonspecific [(123)I]beta-CIT
      binding for the midbrain-pons (V(3)" = [midbrain/pons-occipital]/occipital) was
      used. RESULTS: Mean specific-to-nonspecific ratios showed a 25% higher midbrain
      pons [(123)I]beta-CIT binding in the patients as compared with healthy controls
      (2.26 +/-.37 vs. 1.81 +/-.23, p <.01). The difference remained significant after
      adjustment for clinical variables and controlling for age and gender.
      Stratification of the patients according to onset of the disorder revealed
      significant differences between controls and patients with early (childhood,
      adolescence) but not late (adult) onset of OCD. CONCLUSIONS: The study provides
      evidence of a serotonergic dysfunction in patients with OCD and suggests a
      serotonergic component in the pathophysiology of the disorder.

PMID- 14675806
TI  - Serotonin transporters in obsessive-compulsive disorder: a positron emission
      tomography study with [(11)C]McN 5652.
AB  - BACKGROUND: Serotonergic abnormalities have been hypothesized to contribute to
      obsessive-compulsive disorder (OCD). This study examined whether brain serotonin
      transporter (SERT) availability is altered in OCD using positron emission
      tomography (PET) and the SERT PET radiotracer [(11)C]McN 5652. METHODS: Eleven
      OCD subjects, free of psychiatric medications and comorbid depression, and 11
      matched healthy control subjects underwent PET scans following injection of
      [(11)C]McN 5652 and magnetic resonance imaging (MRI) scans. Total distribution
      volumes (V(T)) were derived by kinetic analysis (one tissue compartment model)
      using the arterial input function. Two measures of SERT availability were
      computed: binding potential (BP) and specific to nonspecific partition
      coefficient (V(3)"). Groups were compared using region of interest (ROI) analysis
      and voxelwise analysis of spatially normalized parametric maps; ROIs were
      selected based on their relatively high SERT density and included subcortical
      (dorsal caudate, dorsal putamen, ventral striatum, midbrain, thalamus) and limbic
      (hippocampus, amygdala, anterior cingulate cortex) regions. RESULTS: No
      significant group differences were observed in [(11)C]McN 5652 BP or V(3)" in the
      ROIs. No significant group differences were detected in the voxelwise analysis of
      BP or V(3)" maps. CONCLUSIONS: OCD without comorbid depression, may not be
      associated with major changes in SERT availability in subcortical and limbic
      regions.

PMID- 14675808
TI  - Reduced heart rate variability in chronic alcohol abuse: relationship with
      negative mood, chronic thought suppression, and compulsive drinking.
AB  - BACKGROUND: Previous research suggests that heart rate variability (HRV) may be
      an important factor in various maladaptive psychological conditions. METHODS:
      This study was conducted to investigate vagal tone assessed as tonic vagally
      mediated heart rate variability in alcoholic (n = 49) and control subjects (n =
      45). RESULTS: Alcoholic subjects had faster heart rate and lower preimaginary
      exposure levels of HRV compared with the control group. An increase in HRV was
      observed in the alcoholic group when subjects were exposed to an imaginary
      alcohol script. Tonic HRV was found to be related inversely to negative mood and
      chronic thought suppression and positively to positive mood. Furthermore, the
      compulsive subscale of the Obsessive Compulsive Drinking Scale (OCDS) was
      inversely related to HRV during the imaginary alcohol exposure. CONCLUSIONS: It
      is concluded that the findings are in agreement with the neurovisceral
      integration model of affective regulation, which claims that dysfunctional
      psychologic states are rooted in an impaired inhibitory mechanism that is
      associated with low HRV.

PMID- 14675807
TI  - Analysis of genetic variations of protein tyrosine kinase fyn and their
      association with alcohol dependence in two independent cohorts.
AB  - BACKGROUND: Decreased sensitivity to and increased tolerance for the effects of
      alcohol is a phenotype, which was shown to be associated with an increased risk
      for alcoholism in humans and was observed in protein tyrosine kinase (PTK) fyn
      knockout mice. METHODS: We performed an association study of genetic variations
      of PTK fyn in 430 alcohol-dependent patients and 365 unrelated control subjects
      from two independent samples. RESULTS: In a combined analysis, we found an
      association of alcohol dependence with the single nucleotide polymorphism (SNP)
      T137346C in the 5' untranslated region (UTR) of the gene. A relevant association
      could be excluded for the remaining two informative SNPs. Selection by phenotype
      showed that a high number of withdrawal symptoms, high amount of alcohol intake,
      and high maximum number of drinks compared with unrelated control subjects was
      associated with the SNP in the 5'-UTR region but not with the remaining SNPs.
      CONCLUSIONS: Our results indicate a possible association of alcohol dependence
      with a genotype of the SNP T137346C of the PTK fyn, with C being the risk allele.

PMID- 14675809
TI  - Abnormal nocturnal melatonin secretion and disordered sleep in abstinent
      alcoholics.
AB  - BACKGROUND: Alcoholic patients show prominent disturbance of sleep as measured by
      electroencephalogram, with difficulties in the onset and maintenance of sleep.
      Given the role of melatonin in the regulation of the sleep-wake cycle, this study
      examined the relationship between nocturnal expression of melatonin and sleep in
      alcoholics as compared with control subjects. METHODS: Alcoholic patients (n =
      11) and comparison control subjects (n = 10) underwent all-night polysomnography
      and serial blood sampling every 30 min from 10:00 PM to 6:30 AM for measurement
      of circulating levels of melatonin and cortisol. RESULTS: Coupled with prolonged
      sleep latency, alcoholics showed lower levels of melatonin during the early part
      of the night and a delay in the onset of the nocturnal plateau or peak value of
      melatonin as compared with control subjects. The nocturnal delay of melatonin
      correlated with prolonged sleep latency. Circulating levels of cortisol were
      lower during the early part of the night and higher in the late part of night in
      the alcoholics as compared with the control subjects. CONCLUSIONS: A delay in the
      nocturnal rise of melatonin may contribute to disordered sleep in chronic
      alcoholics, with implications for the use of melatonin in the treatment of
      insomnia in recovering alcoholics.

PMID- 14675810
TI  - Psychological risk factors for HIV pathogenesis: mediation by the autonomic
      nervous system.
AB  - BACKGROUND: Epidemiologic studies have identified psychological risk factors for
      specific physical diseases, but the biological mechanisms mediating these
      relationships remain poorly defined. METHODS: Social inhibition and autonomic
      nervous system (ANS) activity were assessed on multiple occasions in 54 gay men
      with asymptomatic human immunodeficiency virus (HIV) infection. Following
      baseline ANS assessment, plasma HIV-1 viral load and CD4+ T cell levels were
      monitored for 12-18 months to assess relationships between ANS activity and HIV
      pathogenesis. RESULTS: We confirmed the previously reported relationship between
      socially inhibited temperament and vulnerability to viral pathology. Plasma viral
      load set-point was elevated eight-fold in socially inhibited individuals, and
      these individuals showed poorer virologic and immunologic response to initiation
      of highly active antiretroviral therapy (HAART). Effects were independent of
      duration of infection, HAART regimen, demographic characteristics, and health
      relevant behavior. Neurophysiologic assessments documented elevated ANS activity
      in socially inhibited individuals, and mediational analyses showed that such
      differences could account for 64%-92% of the covariance between social inhibition
      and virologic parameters. CONCLUSIONS: These data provide the first clinical
      evidence that differential neural activity mediates relationships between
      psychological risk factors and infectious disease pathogenesis. Such findings
      also suggest novel targets for adjunctive therapy in long-term control of HIV-1
      disease.

PMID- 14675811
TI  - Adenylate cyclase activity in postmortem brain of suicide subjects: reduced
      response to beta-adrenergic stimulation.
AB  - BACKGROUND: Biochemical research on the etiopathogenesis of affective disorders
      has focused on transduction mechanisms beyond receptors, such as adenylate
      cyclase activity. METHODS: Adenylate cyclase activity (AC) was measured in
      postmortem frontal cortex samples from 11 suicide victims with a firm antemortem
      diagnosis of major depressive disorder and 11 matched control cases. We analyzed
      the basal activity of the enzyme and that following stimulation with forskolin,
      guanine nucleotides, and the beta(1)-adrenoceptor agonist xamoterol. RESULTS: A
      significant negative correlation between the period of tissue storage and the
      response of AC to the different stimuli assayed was observed. No difference was
      found in the levels of basal, forskolin-, and GTPgammaS-stimulated activity
      between control and major depressive disorder cases, both in the drug-free and
      the drug-treated subgroups. In contrast, we found a significant lower response to
      beta(1)-adrenoceptors agonist-stimulated AC activity in the major depressive
      disorder group (p <.01). This pattern of reduced response was also found in the
      subgroup of patients with negative toxicology for antidepressants. CONCLUSIONS:
      These results, directly obtained from the brain of depressed patients, reinforce
      the involvement of noradrenergic neurotransmission in depressive illness. They
      also support the relevance of cyclic adenosine monophosphate signaling pathways
      in the etiopathogenesis of affective disorders.

PMID- 14675812
TI  - Methylphenidate improves response inhibition in adults with attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Response inhibition is an executive function that requires voluntary
      control over responses when there is a change of context. The right inferior
      frontal cortex is necessary for response inhibition, and a deficit in right
      frontostriatal circuitry might underlie attention-deficit/hyperactivity disorder
      (ADHD). Many studies of childhood ADHD have demonstrated impaired response
      inhibition and its amelioration by methylphenidate (MPH). The current study
      tested response inhibition and the effect of MPH in adult ADHD. METHODS: Response
      inhibition was assessed with the "tracking" stop-signal test in 13 adults with a
      diagnosis of ADHD, both while taking and while not taking medication, and 13
      healthy, unmedicated, age- and intelligence quotient-matched control subjects.
      RESULTS: Stop-signal reaction time was significantly slower in unmedicated adults
      with ADHD relative to healthy control subjects, and this deficit was
      significantly ameliorated by medication. CONCLUSIONS: Adult ADHD patients had a
      response inhibition profile similar to that produced by lesions to the right
      inferior frontal cortex, which was remedied by stimulant medication.

PMID- 14675813
TI  - 2H[19F] REDOR for distance measurements in biological solids using a double
      resonance spectrometer.
AB  - A new approach for distance measurements in biological solids employing 2H[19F]
      rotational echo double resonance was developed and validated on 2H,19F-D-alanine
      and an imidazopyridine based inhibitor of the gastric H+/K+-ATPase. The 2H-19F
      double resonance experiments presented here were performed without 1H decoupling
      using a double resonance NMR spectrometer. In this way, it was possible to
      benefit from the relatively longer distance range of fluorine without the need of
      specialized fluorine equipment. A distance of 2.5 +/- 0.3 A was measured in the
      alanine derivative, indicating a gauche conformation of the two labels. In the
      case of the imidazopyridine compound a lower distance limit of 5.2 A was
      determined and is in agreement with an extended conformation of the inhibitor.
      Several REDOR variants were compared, and their advantages and limitations
      discussed. Composite fluorine dephasing pulses were found to enhance the
      frequency bandwidth significantly, and to reduce the dependence of the
      performance of the experiment on the exact choice of the transmitter frequency.

PMID- 14675814
TI  - Random coil carbon chemical shifts of deoxyribonucleic acids.
AB  - The sequence and temperature effects on random coil DNA carbon chemical shifts
      have been investigated using sixteen 17-nucleotide sequences. Temperature effect
      correction parameters have been determined for the aromatic C6/C8 carbons and the
      deoxyribose C1', C2', and C3' carbons. The carbon chemical shifts of a specific
      nucleotide in a random coil sequence have been shown to depend mainly on the type
      of its nearest neighbors. A carbon chemical shift database containing all 64
      different types of triplets has been established for predicting random coil DNA
      carbon chemical shifts. The use of this triplet database for carbon chemical
      shift predictions shows good accuracy with experimental data, with root-mean
      square deviations of 0.09, 0.10, 0.10, and 0.10 ppm and correlation coefficients
      of 0.999, 0.996, 0.978, and 0.974 for C6/C8, C1', C2', and C3', respectively.

PMID- 14675815
TI  - Field-cycling method with central transition readout for pure quadrupole
      resonance detection in dilute systems.
AB  - We present a modification of a field-cycling method which uses the NMR signal of
      the central transition at high field to indirectly detect zero-field quadrupole
      transitions. The quadrupole transitions at zero-field are detected as changes in
      the overall intensity of the central transition signal after the field cycle, and
      the method is relatively immune to lineshape distortions of the central
      transition caused by receiver dead time, frequency response of the probe, longer
      pulse lengths, etc. Cross-polarization with protons is used to enhance the
      central-transition signal and to increase the recycling rate of the experiment.
      The technique is especially useful when mixtures of several species are present.
      In a frozen solution of phenylboronic acid, 11B quadrupole signals of the
      tetrahedral species at 600 kHz and planar-trigonal species at 1450 kHz are
      clearly resolved. The field-cycling approach allows high-sensitivity detection of
      low-frequency quadrupole transitions; the experiment is sensitive enough to study
      boronic-acid protease inhibitors bound to proteins and may possibly be extended
      to lower sensitivity nuclei. The experiments are performed using a low
      temperature field-cycling apparatus, operated at 10-30 K, capable of
      pneumatically moving the sample from the high field of a commercial 500 MHz
      magnet to the area above the top of the magnet where the low field is controlled
      by a pair of Helmholz coils.

PMID- 14675816
TI  - Magnetization recovery for signal enhancement: a fast imaging DEFT-based
      technique.
AB  - This paper describes the development and application of a new fast MRI technique
      based on the DEFT principle. The sequence named MAgnetization RecoverY for Signal
      Enhancement (MARYSE) is composed of two completely symmetric gradient echoes
      separated by a 180 degrees refocusing pulse. The RF pulse scheme, 90 degrees x
      180 degrees y-90 degrees -x enables restoration of the transverse magnetization
      along the longitudinal axis, and consequently artificially increases R1
      relaxation rate. In this sequence, the period between the excitation pulse and
      the restoring pulse (Tem: transverse magnetization evolution time) is very short
      (< 10 ms). This makes possible a significant increase in signal-to-noise ratio,
      even with a relatively short repetition time (20 ms). Simulations were performed
      for different values of Tem and TR at definite T1 and T2 and for different values
      of T1 and T2 at constant Tem and TR. Relevant signal enhancement for species with
      long relaxation time constants as compared to classical gradient echo and fast
      spin-echo imaging was expected. In vitro studies on a fat/water phantom confirmed
      this simulation. Application of MARYSE to mouse brain imaging permitted to
      visualize almost completely cerebrospinal fluid of the ventricles, a signal
      usually partially saturated in fast gradient echo imaging.

PMID- 14675817
TI  - Experimental demonstration of a programmable quantum computer by NMR.
AB  - A programmable quantum computer is experimentally demonstrated by nuclear
      magnetic resonance using one qubit for the program and two qubits for data. A non
      separable two-qubit operation is performed in a programmable way to show the
      successful demonstration. Projective measurements required in the programmable
      quantum computer are simulated by averaging the results of experiments just like
      when producing an effective pure state.

PMID- 14675818
TI  - Homonuclear Hartmann-Hahn transfer with reduced relaxation losses by use of the
      MOCCA-XY16 multiple pulse sequence.
AB  - Homonuclear Hartmann-Hahn transfer is one of the most important building blocks
      in modern high-resolution NMR. It constitutes a very efficient transfer element
      for the assignment of proteins, nucleic acids, and oligosaccharides.
      Nevertheless, in macromolecules exceeding approximately 10 kDa TOCSY-experiments
      can show decreasing sensitivity due to fast transverse relaxation processes that
      are active during the mixing periods. In this article we propose the MOCCA-XY16
      multiple pulse sequence, originally developed for efficient TOCSY transfer
      through residual dipolar couplings, as a homonuclear Hartmann-Hahn sequence with
      improved relaxation properties. A theoretical analysis of the coherence transfer
      via scalar couplings and its relaxation behavior as well as experimental transfer
      curves for MOCCA-XY16 relative to the well-characterized DIPSI-2 multiple pulse
      sequence are given.

PMID- 14675819
TI  - J-modulated ADEQUATE (JM-ADEQUATE) experiment for accurate measurement of carbon
      carbon coupling constants.
AB  - A new method for the accurate determination of carbon-carbon coupling constants
      is described. The method is based on a modified ADEQUATE experiment, where a J
      modulated spin-echo sequence precedes the ADEQUATE pulse scheme. The J-modulation
      and scaling of carbon-carbon couplings is based on simultaneous incrementation of
      13C chemical shift and coupling evolution periods. The time increment for the
      homonuclear carbon-carbon coupling evolution can be suitably scaled with respect
      to the corresponding increment for the chemical shift evolution. Typically a
      scaling factor of 2 to 3 is employed for the measurement of one-bond coupling
      constants, while multiplication by a factor of 10 to 15 is applied when small
      long-range couplings are determined. The same pulse scheme with coupling
      evolution period optimized for one-bond or long-range couplings allows the
      determination of the corresponding carbon-carbon coupling constants. The
      splittings of the ADEQUATE crosspeaks in the F1 dimension yield the appropriately
      multiplied coupling constants.

PMID- 14675820
TI  - Development of a method for the measurement of long-range 13C-1H coupling
      constants from HMBC spectra.
AB  - This paper describes a number of improvements to a method, developed in this
      laboratory and described in J. Magn. Reson. 85 (1989) 111-113, which makes it
      possible to determine values of long-range 13C-1H coupling constants from
      heteronuclear multiple bond correlation (HMBC) spectra. First, it is shown how
      pulsed-field gradients can be introduced into the HMBC experiment without
      perturbing the form of the cross-peak multiplets; a one-dimensional version of
      the experiment is also described which permits the rapid measurement of a small
      number of couplings. Second, the experiment is modified so that one-bond and long
      range cross-peaks can be separated, and so that the one-bond cross-peaks have
      more reliable intensities. Finally, it is shown how these one-bond cross-peaks
      can be used to advantage in the fitting procedure.

PMID- 14675821
TI  - Pulsed optically detected NMR of single GaAs/AlGaAs quantum wells.
AB  - While nuclear magnetic resonance (NMR) is one of the most important experimental
      tools for the analysis of bulk materials, the low sensitivity of conventional NMR
      makes it unsuitable for the investigation of small structures. We introduce an
      experimental scheme that makes NMR spectra of single, nanometer-sized quantum
      wells possible with excellent sensitivity and selectivity while avoiding the
      spectral broadening associated with some alternative techniques. The scheme
      combines optical pumping and pulsed radiofrequency excitation of the nuclei with
      time-resolved detection of the free induction decay through the polarization of
      the photoluminescence.

PMID- 14675822
TI  - Multi-echo imaging in highly inhomogeneous magnetic fields.
AB  - A new pulsed field gradient multi-echo imaging technique to encode position in
      the phase of every echo generated by a CPMG sequence in the presence of a
      strongly inhomogeneous static magnetic field is presented. It was applied to
      improve the sensitivity in an imaging experiment by adding the echo train
      acquired during the CPMG sequence and to spatially resolve relaxation times of
      inhomogeneous specimens using single-sided probes. The sequence was implemented
      in a new bar-magnet MOUSE equipped with a gradient coil system to apply a pulsed
      magnetic field with a constant gradient along one spatial coordinate. An
      important reduction by a factor larger than two orders of magnitude in the
      acquisition time was obtained compared to the previously published single-point
      imaging technique.

PMID- 14675823
TI  - Free radical EPR spectroscopy analysis using blind source separation.
AB  - In this paper, we propose a novel approach for electron paramagnetic resonance
      (EPR) mixture spectra analysis based on blind source separation (BSS) technique.
      EPR spectrum of a free radical is often superimposed by overlapping spectra of
      other species. It is important and challenging to accurately identify and
      quantify the 'pure' spectra from such mixtures. In this study, an automated BSS
      method implementing independent component analysis is used to extract the
      components from mixed EPR spectra that contain overlapping components of
      different paramagnetic centers. To apply this method, there is no requirement to
      know the component spectra or the number of components in advance. The method is
      applied to analyze free radical EPR spectra which are collected from standard
      chemical system, cultured cell suspense, and ex vivo rat kidneys by spin trapping
      EPR technique. Results show that the BSS method proposed here is capable of
      identifying the component EPR spectra from mixtures with unknown compositions.
      The BSS technique can offer powerful aids in resolving spectral overlapping
      problems in general EPR spectroscopy analysis.

PMID- 14675824
TI  - A continuous-wave and pulsed electron spin resonance spectrometer operating at
      275 GHz.
AB  - An electron paramagnetic resonance (EPR) spectrometer is described which allows
      for continuous-wave and pulsed EPR experiments at 275 GHz (wavelength 1.1 mm).
      The related magnetic field of 9.9 T for g approximately 2 is supplied by a
      superconducting solenoid. The microwave bridge employs quasi-optical as well as
      conventional waveguide components. A cylindrical, single-mode cavity provides a
      high filling factor and a high sensitivity for EPR detection. Even with the
      available microwave power of 1 mW incident at the cavity a high microwave
      magnetic field B1 is obtained of about 0.1 mT which permits pi/2-pulses as short
      as 100 ns. The performance of the spectrometer is illustrated with the help of
      spectra taken with several samples.

PMID- 14675825
TI  - Multiple-spin analysis of chemical-shift-selective (13C, 13C) transfer in
      uniformly labeled biomolecules.
AB  - Chemical-shift-selective (13C, 13C) polarization transfer is analyzed in
      uniformly labeled biomolecules. It is shown that the spin system dynamics remain
      sensitive to the distance of interest and can be well reproduced within a quantum
      mechanical multiple-spin analysis. These results lead to a general approach on
      how to describe chemical-shift-selective transfer in uniformly labeled systems.
      As demonstrated in the case of ubiquitin, this methodology can be used to detect
      long-range distance constraints in uniformly labeled proteins.

PMID- 14675826
TI  - Equi-ripple design of quadratic-phase RF pulses.
AB  - An improved strategy for the design of quadratic-phase RF pulses with high
      selectivity and broad bandwidths using the Shinnar-Le Roux (SLR) transformation
      is proposed. Unlike previous implementations, the required quadratic-phase finite
      impulse response (FIR) filters are generated using the complex Remez exchange
      algorithm, which ensures an equi-ripple deviation from the ideal response
      function. It is argued analytically that quadratic-phase pulses are near-optimal
      in terms of minimising the B1-amplitude for a given bandwidth and flip angle.
      Furthermore, several parameter relations are derived, providing practical design
      guidelines. The effectiveness of the proposed design method is demonstrated by
      examples of excitation and saturation pulses applied in vitro and in vivo.

PMID- 14675827
TI  - Improved multiplicity-edited ADEQUATE experiments.
AB  - A very simple strategy is proposed to extract carbon multiplicity information
      along with the classic knowledge of carbon-carbon connectivities in ADEQUATE
      experiments without affecting the sensitivity ratios of the original pulse
      schemes. These new multiplicity-edited ADEQUATE experiments prove to be highly
      helpful for complete 1H and 13C resonance assignment and also for automated and
      easy spin system characterization of samples at natural abundance, using a single
      NMR experiment.

PMID- 14675828
TI  - Measuring protein self-diffusion in protein-protein mixtures using a pulsed
      gradient spin-echo technique with WATERGATE and isotope filtering.
AB  - Here we report a modified pulsed gradient spin-echo (PGSTE) pulse sequence to
      measure diffusion coefficients. This approach incorporates WATERGATE combined
      with isotopic filtering into a standard PGSTE experiment. Doing this eliminates
      much of the disadvantages from the combination of diffusion encoding and
      heteronuclear selection intervals and allows for facile modification of the
      diffusion pulse sequence with flexibility of the time period between RF pulses.
      The new diffusion pulse sequence is demonstrated using an 15N-labeled peptide and
      an 15N-labeled protein in a mixture with a protein of similar size.

PMID- 14675829
TI  - Partial purification of antibacterial proteinaceous factors from erythrocytes of
      Oncorhynchus mykiss.
AB  - Antimicrobial peptides are natural antibiotics known to be present in both
      myeloid cells and epithelial surfaces of vertebrates. Nevertheless, the reports
      of antimicrobial peptides isolated from blood cells of teleosts are scarce. In
      this paper we show that acid-soluble erythrocyte extracts from rainbow trout,
      Oncorhynchus mykiss, display antibacterial activity against Planococcus citreus
      on a radial diffusion assay. Following tC18 solid phase extraction, cationic
      exchange chromatography and C18 reversed phase HPLC, two groups of fractions with
      antibacterial properties were obtained. This antibacterial activity is
      thermostable and susceptible to digestion by proteinase K, thus showing that the
      antibacterial agents have a proteinaceous nature. The factors eluted from a C18
      column with circa 33% acetonitrile are active against P. citreus and Escherichia
      coli, with minimal inhibitory concentrations in the range 7-14 microg ml(-1) and
      14-28 microg ml(-1), respectively; the ones eluted with approximately 44%
      acetonitrile on the same column only displayed activity against P. citreus, with
      a minimal inhibitory concentration of 1-2 microg ml(-1). These results raise the
      possibility that trout erythrocytes may contain antimicrobial factors not
      previously considered to be part of the innate immune system.

PMID- 14675830
TI  - Cloning and analysis of expression of a gilthead sea bream (Sparus aurata) Mx
      cDNA.
AB  - In the current work, we have cloned and sequenced the full cDNA for a Mx protein
      in the gilthead sea bream (Sparus aurata) by RACE PCR. The Mx cDNA of 2182 bp
      contained an open reading frame of 1857 bp that codes for a protein of 618 aa.
      Within the coding sequence, characteristic features of Mx proteins were found,
      such as a tripartite guanosine-5'-triphosphate (GTP)-binding motif (GXXXSGKS/T,
      DXXG and T/NKXD), the signature of the dynamin family, LPRG(S/K)GIVTR, and a
      sequence that codes for a leucine zipper at the C-terminal region of the protein.
      An RT-PCR was optimised to estimate the level of expression of Mx protein in sea
      bream. Through this method we determined that Mx is constitutively expressed in
      head kidney, liver, spleen, heart, gills, muscle and brain of healthy sea bream.
      Intramuscular challenge of sea bream with polyinosinic:polycytidylic acid (Poly
      I:C) up-regulated Mx expression in liver, head kidney, spleen and muscle.
      Constitutive expression was also found in isolated head kidney macrophages and
      blood leukocytes. This expression was significantly up-regulated by addition of
      Poly I:C. Mx was not constitutively expressed in the sea bream established cell
      line, SAF-1, but Poly I:C and nodavirus were also capable of inducing Mx
      expression in this cell line.

PMID- 14675831
TI  - Nonspecific immune response of rainbow trout (Oncorhynchus mykiss Walbaum) in
      relation to different status of vitamin E and highly unsaturated fatty acids.
AB  - This study was designed to examine the effects of dietary vitamin E (VE) on
      modulation of immune responses when supplied with two levels of n-3 highly
      unsaturated fatty acids (n-3 HUFA) in rainbow trout, Oncorhynchus mykiss. Six
      semipurified diets were prepared containing three levels of dietary VE (0, 100 or
      1000 mg alpha-tocopheryl acetate kg(-1) diet) and n-3 HUFA either at 20 or 48% of
      dietary lipid provided from fish oil or docosahexaenoic acid (DHA) concentrated
      fish oil respectively. The diets were fed to rainbow trout (100 g initial mean
      weight) for 15 weeks. The VE, vitamin C (VC) content in plasma and tissues and
      the nonspecific immune responses, both humoral (alternative complement activity,
      total immunoglobulin) and cellular (phagocytosis, nonspecific cytotoxicity) were
      examined. VE contents in the kidney reflected the dietary input but were lower in
      fish fed 48% n-3 HUFA diets, and could have impaired some of immune responses
      compared to fish fed 20% n-3 HUFA. VC contents in kidney followed the same
      pattern as VE. Both humoral and cellular immune functions deteriorated in fish
      fed VE deficient diets whereas improvement in most of the parameters corresponded
      to its supplementation. However, the higher dose of dietary VE did not
      substantially enhance the responses assayed compared to the 100 mg dose. Besides
      clearly indicating the role of VE in maintaining the immune functions in fish in
      relation to dietary n-3 HUFA, this study has revealed that optimum health
      benefits could be achieved when VE is maintained slightly above the levels
      generally recommended for normal growth.

PMID- 14675832
TI  - The immunosuppressive effect of alpha-permethrin on Indian major carp, rohu
      (Labeo rohita Ham.).
AB  - The immunosuppressive effects of bath exposure to a sub lethal concentration of
      the synthetic pyrethroid alpha-permethrin (3.05 x 10(-4) mg l(-1)) in the Indian
      Major carp, Labeo rohita was studied after 45 days' exposure. In some groups, the
      effects of alpha-permethrin on non-specific defences and serum enzymes of carp
      were investigated after challenge with Aeromonas hydrophila. Several nonspecific
      immune responses and serum enzymes were reduced after exposure of alpha
      permethrin. Bactericidal activity of rohu serum was reduced significantly in
      pesticide and bacteria treated fish. The Glutamic Oxaloacetate Transaminase (GOT)
      and Glutamic Pyruvate Transaminase (GPT) activity were increased in
      immunosuppressed fish. Blood glucose level was elevated significantly and Hb% was
      reduced significantly in pesticide and bacteria treated fishes as compared to the
      negative control.

PMID- 14675833
TI  - Environmental factors influencing the immune responses of the common European
      starfish (Asterias rubens).
AB  - The influence of handling, salinity, temperature, parasitism, and gender on the
      immune responses (reactive oxygen species (ROS) production and coelomic
      amoebocyte concentration (CAC) of the starfish Asterias rubens was investigated
      in experimental conditions. Additionally, a year-round monthly survey in two
      distant sites was conducted in order to understand which of these factors most
      influences the immunity of A. rubens in field conditions. All considered factors,
      except gender and handling stress, influenced the studied immune responses of A.
      rubens in experimental conditions. Amoebocyte ROS production was increased at low
      salinity and at the lowest temperature tested (6 degrees C). Amoebocyte
      concentration in the coelomic fluid was increased in starfish infested by the
      ciliate Orchitophrya stellarum. However, among all these factors, only
      temperature could be linked with the variability in ROS production measured in
      the field during the monthly survey. The variability in amoebocyte concentration
      in the field does not seem to be linked to any of the factors considered in this
      study; it appears to reflect mostly an inter-individual variation rather than
      seasonal fluctuations. Recommended periods and indicative values of immune
      responses are proposed for field studies using A. rubens.

PMID- 14675834
TI  - Immune response of gilt-head seabream (Sparus aurata) to antigens from
      Photobacterium damselae subsp. piscicida.

PMID- 14675835
TI  - Antigenic cross-reactivity of crustacean haemocytes using monoclonal antibodies
      produced against haemocytes of shrimp (Litopenaeus vannamei).
AB  - Eight monoclonal antibodies produced against haemocytes of shrimp (Litopenaeus
      vannamei) were used to research the antigenic cross-reactivity of crustacean
      haemocytes. 2C3 cross-reacted with the haemocytes of all the experimental
      animals, while 1H8 and 2C11 did not cross-react with the experimental animals.
      The other five monoclonal antibodies cross-reacted with some of the experimental
      animals.

PMID- 14675837
TI  - Efficacy of various amendments for amelioration of fly-ash toxicity: growth
      performance and metal composition of Cassia siamea Lamk.
AB  - Plants of Cassia siamea Lamk were grown in garden soil (control), fly-ash (100%)
      and fly-ash amended by various ameliorants (cowdung manure, press-mud, garden
      soil; 1:1, w/w). The plants survived in fly-ash (100%) though their growth was
      less in comparison to the treatments. Fly-ash+press-mud (1:1, w/w) proved to be
      the best combination as growth (total biomass, leaf number, photosynthetic area,
      total chlorophyll and protein) was significantly high in this treatment followed
      by cowdung manure and garden soil. Leaves and roots accumulated significant
      amount of Cu, Zn, Ni and and Fe. However, the concentration of all the metals was
      more in roots than leaves except Ni. Although, fly-ash contains high amount of
      metals but the metal uptake was more in the plants grown in fly-ash+press-mud
      mixture. Inspite of high metal availability in fly-ash and press-mud mixture,
      plant growth was good. This might be attributed to the some metal detoxification
      mechanism active in this treatment. The present study concluded that C. siamea
      seems to be a suitable plant for developing a vegetation cover on fly-ash dumps.

PMID- 14675838
TI  - Investigating the sources of the mutagenic activity found in a river using the
      Salmonella assay and different water extraction procedures.
AB  - In the routine Sao Paulo state (Brazil) surface water quality-monitoring program,
      which includes the Salmonella microsome mutagenicity assay as one of its
      parameters, a river where water is taken and treated for drinking water purposes
      has repeatedly shown mutagenic activity. A textile dyeing facility employing azo
      type dyes was the only identifiable source of mutagenic compounds. We extracted
      the river and drinking water samples with XAD4 at neutral and acidic pH and with
      blue rayon, which selectively adsorbs polycyclic compounds. We tested the
      industrial effluent, raw, and treated water and sediment samples with YG1041 and
      YG1042 and compared the results with the TA98 and TA100 strains. The elevated
      mutagenicity detected with YG-strains suggested that nitroaromatics and/or
      aromatic amines were causing the mutagenicity detected in the samples analyzed.
      Positive responses for the blue rayon extracts indicated that mutagenic
      polycyclic compounds were present in the water samples analyzed. The mutagen or
      mixture of mutagens present in the effluent and water samples cause mainly
      frameshift mutations and are positive with and without metabolic activation. The
      Salmonella assay combined with different extraction procedures proved to be very
      useful in the identification of the origin of the pollution and in the
      identification of the classes of chemical compounds causing the mutagenic
      activity in the river analyzed.

PMID- 14675839
TI  - Serum concentrations of perfluorooctanesulfonate and other fluorochemicals in an
      elderly population from Seattle, Washington.
AB  - Perfluorooctanesulfonyl fluoride (POSF, C8F17SO2F) related-materials have been
      used as surfactants, paper and packaging treatments, and surface (e.g., carpet,
      textile, upholstery) protectants. A metabolite, perfluorooctanesulfonate (PFOS,
      C8F17SO3-), has been identified in the serum and liver of non-occupationally
      exposed humans and wildlife. Because of its persistence, an important question
      was whether elderly humans might have higher PFOS concentrations. From a
      prospective study designed to examine cognitive function in the Seattle (WA)
      metropolitan area, blood samples were collected from 238 dementia-free subjects
      (ages 65-96). High-pressure liquid chromatography-electrospray tandem mass
      spectrometry determined seven fluorochemicals: PFOS; N-ethyl
      perfluorooctanesulfonamidoacetate; N-methyl perfluorooctanesulfonamidoacetate;
      perfluorooctanesulfonamidoacetate; perfluorooctanesulfonamide;
      perfluorooctanoate; and perfluorohexanesulfonate. Serum PFOS concentrations
      ranged from less than the lower limit of quantitation (3.4 ppb) to 175.0 ppb
      (geometric mean 31.0 ppb; 95% CI 28.8-33.4). An estimate of the 95% tolerance
      limit was 84.1 ppb (upper 95% confidence limit 104.0 ppb). Serum PFOS
      concentrations were slightly lower among the most elderly. There were no
      significant differences by sex or years residence in Seattle. The distributions
      of the other fluorochemicals were approximately an order of magnitude lower.
      Similar to other reported findings of younger adults, the geometric mean serum
      PFOS concentration in non-occupational adult populations likely approximates 30
      40 ppb with 95% of the population's serum PFOS concentrations below 100 ppb.

PMID- 14675840
TI  - Induced alkoxyresorufin-O-dealkylases in tilapias (Oreochromis niloticus) from
      Guandu river, Rio de Janeiro, Brazil.
AB  - The activity of fish monooxygenases has been extensively used as a monitoring
      tool to detect contamination of water bodies by cytochrome P450-inducing agents.
      In this study we evaluated the activities of ethoxy- (EROD), methoxy- (MROD) and
      pentoxy- (PROD) resorufin-O-dealkylases in the liver of Nile tilapias
      (Oreochromis niloticus) collected at the Guandu river, at a reference clean site
      (Lake 1) and at two other sampling sites (Lakes 2 and 3) in Rio de Janeiro state,
      Brazil. Alkoxyresorufin-O-dealkylases were measured fluorimetrically in the
      hepatic S9 fraction. EROD (17.7-fold), MROD (14.2-fold) as well as PROD
      activities were considerably higher in tilapias from Guandu river. A moderate
      increase of EROD (5.0-fold) and MROD (5.4-fold) was also found in tilapias from
      Lake 3. These findings suggest that Guandu river watershed, the main source of
      urban drinking water supply in Rio de Janeiro, is polluted with CYP1A-inducing
      xenobiotics. Furthermore, we also found a good linear relationship between EROD
      and MROD, a finding that agrees with the hypothesis that the two reactions are
      catalysed by the same CYP1A isoform in O. niloticus.

PMID- 14675841
TI  - Screening organic micropollutants in surface waters by SPE extraction and
      ecotoxicological testing.
AB  - Complex mixtures of toxic substances occurring in surface waters are difficult to
      characterise by chemical analyses because each compound occurs at a very low
      concentration and requires a specific analytical method to be identified.
      Ecotoxicological tests on water extracts can be used as a screening tool to
      evaluate quickly and simply the overall quality of a water body with regard to
      micropollutant contamination. In this work, a pre-concentration procedure based
      on solid-phase extraction (SPE), suitable for both biological testing and
      analytical determination, is proposed. The extraction procedure is an improved
      version of a methodology used to evaluate the toxicity of organic micropollutants
      occurring in surface waters. It offers the advantage of using disposable
      commercial cartridges, which are easier to manage than the columns prepared with
      macromolecular resins. Water extracts from two representative Italian rivers,
      characterised by a different gradient of potential contamination and prepared
      according to the new concentration techniques, are used. The acute toxicity of
      the water extracts is tested on Daphnia magna and the bioluminescence inhibition
      in Vibrio fischeri. Criteria based on the concentration factor (CF) are proposed
      for assessing the hazard to aquatic life due to the exposure to toxic substances
      in surface waters. The aim of hazard ranking is to focus analytical efforts
      towards those samples that show the highest toxic potential.

PMID- 14675842
TI  - Analysis of serpentinophytes from north-east of Portugal for trace metal
      accumulation--relevance to the management of mine environment.
AB  - In north-east of Portugal, the serpentinized area is about 8000 ha with a
      characteristic geology and flora. The serpentine plant community and respective
      soils were analyzed to examine the trace metal budget in different tissues of the
      plants exhibiting resistance to trace metals. One hundred and thirty five plant
      species belonging to 39 families and respective soils have been analyzed for
      total Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn. Substantial amounts of Ni, Cr, Co and Mn
      were detected in plant tissues which are listed below: NI: Alyssum serpyllifolium
      (38105); Bromus hordeaceus (1467); Linaria spartea (492); Plantago radicata
      (140); Lavandula stoechas (118) and Cistus salvifolius (114); CR: L. spartea
      (706.7); Ulmus procera (173.4); A. serpyllifolium (129.3); Cistus ladanifer
      (40.8); L. stoechas (29.5); P. radicata (27.81); Setariopsis verticillata (25.7);
      Plantago lanceolata (24); Digitalis purpurea (23.4); Logfia minima (23.1);
      Arenaria querioides (23); Hieracium peleteranum (22.7); Arenaria montana (14.5);
      CO: A. serpyllifolium (145.1); L. spartea (63.2); P. radicata (10.4); H.
      peleteranum (7.3); Lepidium heterophyllum (6.9); A. querioides (6.6); C.
      salvifolius (6.5); C. ladanifer (6.3); L. stoechas (6.1); Anthyllis lotoides
      (6.1); L. minima (6.1); Euphorbia falcata (5.7) and B. hordeaceus (5.6); MN: A.
      serpyllifolium (830); L. spartea (339); L. stoechas (187.1); L. minima (182.7);
      Castanea sativa (125); Spergula pentandra (124); P. radicata (119); Cytisus
      striatus (115.4); Quercus pyrenaica (110); Teucrium scorodonia (109.4); Fraxinus
      vulgaris (109); Anthyllis sampaiana (108); Quercus ilex (108). The significance
      of serpentine flora, need for conservation of these fragile and environmentally
      invaluable plant resources for possible use for in situ remediation of
      metalliferous substrates are presented in this paper.

PMID- 14675843
TI  - Development of a terrestrial vertebrate model for assessing bioavailability of
      cadmium in the fence lizard (Sceloporus undulatus) and in ovo effects on
      hatchling size and thyroid function.
AB  - In the terrestrial environment, standardized protocols are available for
      measuring the exposure and effects of contaminants to invertebrates, but none
      currently exist for vertebrates. In an effort to address this, we proposed that
      developing lizard embryos may be used as a terrestrial vertebrate model. Lizard
      eggs may be particularly susceptible to soil contamination and in ovo exposure
      may affect hatchling size, mortality, as well as thyroid function. Toxicant
      induced perturbations of thyroid function resulting from in ovo chemical exposure
      may result in toxicity during the critical perinatal period in reptiles.
      Fertilized Eastern fence lizard (Sceloporus undulatus) eggs were placed in
      cadmium (Cd)-spiked expanded perlite (0, 1.48, 14.8, 148, 1480, 14,800 microg
      Cd/g, nominal concentrations), artificially incubated at 28 degrees C, and
      examined daily for mortality. Whole lizard hatchlings as well as failed hatches
      were homogenized in ethanol and the homogenate was divided for Cd body residue
      analysis and thyroid hormone (triiodothyronine (T3) and thyroxine (T4)) analyses.
      Acute mortality was observed in the two highest doses (1480 and 14800 microg
      Cd/g). Cadmium body residues showed a higher internal concentration with
      increasing exposure concentration indicating uptake of Cd. There was a decrease
      in T3:T4 ratio at the highest surviving dose (148 microg Cd/g), however, there
      were no differences observed in hatchling size measured as weight and snout-vent
      length, or in whole body thyroid hormone levels. In summary, this study has shown
      Cd amended to a solid phase representing soil (perlite) can traverse the thin,
      parchment-like shell membrane of the fence lizard egg and bioaccumulate in lizard
      embryos. We believe this study is a good first step in investigating and
      evaluating this species for use as a model.

PMID- 14675844
TI  - Contamination by mercury and cadmium in the cetacean products from Japanese
      market.
AB  - Cetaceans hunted coastally in Japan include several species of odontocete
      (dolphins, porpoises and beaked whales), and fresh and frozen red meat and
      blubber, as well as boiled internal organs, such as liver, lung, kidney and small
      intestine, are still sold for human consumption. Furthermore, red meat and
      blubber products originating from mysticete minke whales caught in the Antarctic
      and Northern Pacific are also sold for human consumption. We surveyed mercury and
      cadmium contamination levels in boiled liver, lung, kidney and red meat products
      being marketed in Japanese retail outlets. We also analyzed the DNA of these
      products to obtain information concerning gender and species. Total mercury (T
      Hg) and methyl mercury (M-Hg) contamination levels in all the cetacean products
      were markedly higher in odontocete species than in mysticete species, and
      slightly higher in females than in males. T-Hg contamination in the organs was
      seen in the following order: boiled liver>boiled kidney=boiled lung>red meat. In
      particular, T-Hg concentrations in the boiled liver were high enough to cause
      acute intoxication even from a single ingestion: the mean +/-SD (range) of T-Hg
      was 388+/-543 (0.12-1980) microg/wetg. In contrast, although M-Hg contamination
      in the liver was not markedly higher than that in other organs, M-Hg
      contamination was in the following order: boiled liver>odontocete red meat>boiled
      kidney>boiled lung. The contamination levels of T-Hg and M-Hg in odontocete red
      meat, the most popular whale product, were 8.94+/-13.3 and 5.44+/-5.72
      microg/wetg, respectively. These averages exceeded the provisional permitted
      levels of T-Hg (0.4 microg/wetg) and M-Hg (0.3 microg/wetg) in marine foods set
      by the Japanese Ministry of Health, Labor and Welfare by 22 and 18 times,
      respectively, suggesting the possibility of chronic intoxication by T-Hg and M-Hg
      with frequent consumption of odontocete red meat. Cadmium contamination levels in
      boiled liver, kidney and lung were 8.59+/-12.0, 10.4+/-8.6 and 1.66+/-1.27
      (microg/wetg), respectively.

PMID- 14675845
TI  - Adaptation of Biscutella laevigata L, a metal hyperaccumulator, to growth on a
      zinc-lead waste heap in southern Poland. I: Differences between waste-heap and
      mountain populations.
AB  - Biscutella laevigata is an herbal member of the Brasicacae family and a typical
      mountain species. It has recently been identified as a hyperaccumulator of lead,
      cadmium and thallium. Its northern reach runs through Poland, where it is found
      only in the west Tatra Mountains and on calamine waste heaps in the vicinity of
      Olkusz (Cracow--Silesian Highland). The peculiar distribution of this species in
      Poland prompted us to undertake studies to identify the traits that allow this
      typically mountain species to grow so robustly on industrial waste heaps near
      zinc and lead smelters in the vicinity of Olkusz. Populations of B. laevigata
      from waste heaps and the Tatra Mountains were compared both under field (natural)
      conditions and during cultivation of successive generations under laboratory
      conditions. It was found that the mountain and waste-heap populations of B.
      laevigata differed significantly. The plants in the mountain population had
      thicker leaves covered with cutin and a small number of hairs, whereas the plants
      from the waste-heap population had thin leaves covered with numerous hairs. The
      difference in leaf thickness between the two populations (0.15 mm on average) was
      due to increased dimensions of palisade mesophyl cells whereas the number of
      cells in their leaves remained similar. These traits were hereditary. This
      indicates that two geographically distant populations of plants followed two
      different evolutionary paths to adapt to xerothermic conditions. Moreover, it was
      shown that the waste-heap population of B. laevigata is more tolerant to heavy
      metals (lead, zinc and cadmium). In the presence of both zinc and lead, growth of
      the waste-heap plants was stimulated, while under the same conditions, growth of
      the mountain population was inhibited lower than 50%. This adaptation facilitates
      the growth of this population on industrial waste heaps. Our studies show that B.
      laevigata is a valuable species very well-suited for use in the recultivation of
      areas containing high levels of heavy metals--the waste-heap population of this
      species is particularly valuable.

PMID- 14675846
TI  - Assessment of bioavailable PAH, PCB and OCP concentrations in water, using
      semipermeable membrane devices (SPMDs), sediments and caged carp.
AB  - Bioavailable water concentrations of polycyclic aromatic hydrocarbons (PAHs),
      polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) were
      assessed at several freshwater sites in and around the city of Amsterdam. Carp
      (Cyprinus carpio) were caged for 4 weeks at 10 sites, together with semipermeable
      membrane devices (SPMDs). In addition, sediment samples were taken at each site.
      SPMDs and sediments were analysed for PAHs, PCBs and OCPs. Carp muscle tissues
      were analysed for PCBs and OCP, while PAH metabolites were assessed in fish bile.
      Contaminant concentrations in the water phase were estimated using three
      different methods: 1. Using fish tissue concentrations and literature
      bioconcentration factors (BCFs), 2. Using SPMD levels and a kinetic SPMD uptake
      model, and 3. Using sediment levels and literature sorption coefficients
      (K(oc)s). Since PAH accumulation in fish is not considered an accurate indicator
      of PAH exposure, calculated aqueous PAH concentrations from SPMD data were
      compared with semiquantitatively determined biliary PAH metabolite levels.
      Contaminant concentrations in the water phase estimated with fish data (Cw(fish))
      and SPMD data (Cw(spmd)) were more in line for compounds with lower K(ow) than
      for compounds with higher K(ow) values. This indicates that the assumption of
      fish-water sorption equilibrium was not valid. At most sites, sediment-based
      water levels (Cw(sed)) were comparable with the Cw(spmd), although large
      differences were observed at certain sites. A significant correlation was
      observed between biliary PAH metabolite levels in fish and aqueous PAH
      concentrations estimated with SPMD data, suggesting that both methods may be
      accurate indicators of PAH exposure in aquatic ecosystems.

PMID- 14675847
TI  - Mechanism of concentration addition toxicity: they are different for nonpolar
      narcotic chemicals, polar narcotic chemicals and reactive chemicals.
AB  - According to the toxicity mechanism of the individual chemicals, the
      concentration addition toxicity mechanism is revealed for nonpolar-narcotic
      chemical mixtures, polar-narcotic-chemical mixtures and reactive-chemical
      mixtures, respectively. For nonpolar-narcotic-chemical mixtures, the partitioning
      of individual chemicals from water to biophase was determined, and the result
      shows that their concentration additive effect results from no competitive
      partitioning among individual chemicals. For polar-narcotic-chemical mixtures,
      their toxicity are contributed by two factors (the total baseline toxicity and
      the hydrogen bond donor activity of individual chemicals), and it is the
      concentration additive effect for either of these two factors that leads to their
      concentration addition toxicity. In addition, the interactions between the
      reactive chemicals and the biological macromolecules are discussed thoroughly.
      The results suggest that the net effect of these interactions is zero, and it is
      this zero net effect that leads to the concentration addition toxicity mechanism
      for reactive-chemical mixtures.

PMID- 14675848
TI  - Myocardial beta-1 adrenoceptor down-regulation in aging and heart failure:
      implications for beta-blocker use in older adults with heart failure.
AB  - Heart failure is associated with increased sympathetic nervous stimulation that
      results in down-regulation of myocardial beta-1 receptors. The failing heart
      might depend more on beta-2 receptors for positive inotropic support than the
      normal heart. Suppression of both beta-1 and beta-2 adrenoceptors by a non
      selective beta-blocker, such as carvedilol, is likely to eliminate the failing
      heart's much needed inotropic support, resulting in an exacerbation of symptoms.
      Use of a beta-1 selective blocker, such as metoprolol, on the other hand, is
      likely to be well tolerated. Unlike carvedilol, the use of metoprolol is
      associated with up-regulation of beta-1 receptors. The clinical significance of
      the pharmacodynamic differences between these two beta-blockers in terms of their
      short-term hemodynamic and long-term beneficial effects is not clearly
      understood. However, in clinical trials, both carvedilol and metoprolol improved
      left ventricular function, heart failure symptoms and survival. Both drugs are
      well tolerated as well. Aging itself is associated with elevated myocardial and
      serum norepinephrine levels, which is associated with down-regulation of beta-1
      receptors. In this article, we reviewed the literature to examine the clinical
      implications of this dual (age- and heart failure-related) sympathetic
      stimulation and beta-1 receptor down-regulation on selection of beta-blockers in
      older adults with heart failure.

PMID- 14675849
TI  - Selection of endpoints for heart failure clinical trials.
AB  - In assessing the efficacy and the safety of a new drug, randomized clinical
      trials represent the standard scientific method. The selection of the best
      response variables in a clinical trial of a treatment in congestive heart failure
      patients is often not straightforward; the primary end point of a trial should be
      clinically relevant, directly related to the primary goal of the trial, and with
      favorable distributional properties. All-cause mortality is undoubtedly the most
      unbiased endpoint, but there is interest both in assessing cause-specific
      mortality and hospitalization rate and in evaluating 'soft' endpoints (functional
      status, exercise tolerance); the latter, in fact, are clinically relevant and
      potentially more useful in mild heart failure patients. Physiopathologic
      variables (e.g. left ventricular function) could provide information on drug
      action mechanism. In this paper, several recent large clinical trials are
      reviewed and the advantages and drawbacks of the response variables used, are
      analyzed.

PMID- 14675850
TI  - Selective beta1-blockade attenuates post-infarct remodelling without improvement
      in myocardial energy metabolism and function in rats with heart failure.
AB  - OBJECTIVE: To investigate in vivo effects of long-term selective beta1-blockade
      on cardiac energy metabolism, remodelling, function and plasma cytokines in a rat
      model of post-infarct congestive heart failure (CHF). METHODS: Myocardial
      infarction (MI) was induced in male rats by ligation of the left coronary artery.
      Three different groups of rats were studied, MI rats treated with metoprolol
      (n=17), MI rats treated with saline (n=14) and sham-operated rats (n=12). The
      treatment with metoprolol 1 mg/kg/h was initiated in the third week post-infarct
      for a period of 6 weeks. All rats were investigated non-invasively with volume
      selective 31P magnetic resonance spectroscopy and echocardiography for evaluation
      of left ventricular (LV) energy metabolism, morphology and function. Plasma
      concentration of IL-1beta and IL-6 and density of beta-adrenergic receptors were
      analyzed. RESULTS: Metoprolol attenuated the increase in LV dimensions and
      volumes. Treatment with metoprolol had no effect on PCr/ATP and LV function.
      Plasma level of IL-1beta was higher and IL-6 was lower in the metoprolol group.
      Density of beta-adrenergic receptors was similar in all three groups. CONCLUSION:
      Selective beta1-blockade in rats with chronic CHF attenuates post-infarct
      structural remodelling, without concomitant improvement in myocardial energy
      metabolism and function. Improvements in myocardial energy metabolism and
      function do not precede and are not a prerequisite for an anti-remodelling effect
      of beta1-blockade in the setting of chronic CHF.

PMID- 14675851
TI  - Quantitative analysis of peroxisome proliferator-activated receptor gamma
      (PPARgamma) expression in arteries and hearts of patients with ischaemic or
      dilated cardiomyopathy.
AB  - PPARgamma, a nuclear transcription factor, is expressed in various cells within
      the vasculature and in cardiomyocytes. It has been suggested that PPARgamma is
      involved in atherogenesis and in cardiac hypertrophy. Therefore, we sought to
      quantify PPARgamma mRNA in coronary arteries, the aorta and left ventricular
      specimens from patients with ischaemic (CHD) and dilated cardiomyopathy (CMP).
      Using real-time PCR, we were able to demonstrate the expression of PPARgamma in
      all of the human specimens. The lowest expression of PPARgamma was detected in
      the aorta specimens of both groups (this was set to one). In comparison, the
      expression in coronary arteries was 2.32-fold in CHD- and 3.78-fold in CMP
      specimens and in the left ventricle specimens, 2.12-fold in CHD- and 3.51-fold in
      CMP. Samples from CHD patients showed a higher expression of PPARgamma in all of
      the samples compared to those from CMP patients (aorta: 1.99-fold; coronary
      arteries: 1.35; left ventricles: 1.23). PPARgamma levels were not significantly
      correlated to CD 36 expression values in any group, suggesting that higher levels
      of PPARgamma are not principally due to increased PPARgamma expression in
      macrophages. This was confirmed by immunohistochemical analysis, which showed
      that PPARgamma is also located in the smooth muscle layer and in cardiomyocytes.
      In conclusion, our observations of increased PPAR mRNA expression in the coronary
      arteries and left ventricles from CHD and CMP patients suggest an important
      function of this nuclear receptor in the pathogenesis of heart disease.

PMID- 14675852
TI  - The effects of acute afterload change on systolic ventricular function in
      conscious dogs with normal vs. failing hearts.
AB  - BACKGROUND: To date, no data exist on the linearity and, therefore, the
      usefulness of the preload recruitable stroke work (PRSW) and end-systolic
      pressure-volume (ESPVR) relationships during acute afterload changes in heart
      failure. AIMS: Our aim was, therefore, to characterize both relationships in a
      model of ventricular pacing induced heart failure at baseline and during acute
      changes in afterload. METHODS: Dynamic left ventricular volume and transmural
      pressure were measured in 10 conscious dogs using sonomicrometry and
      micromanometry under control conditions and during heart failure produced by 3
      weeks of rapid right ventricular pacing. Afterload was varied from baseline with
      intravenous infusions of nitroprusside and phenylephrine. Left ventricular
      function was assessed using the PRSW and ESPVR relationships. RESULTS: Cardiac
      output demonstrated a linear inverse relationship with afterload in both normal
      and failing hearts (r2>0.5, P<0.001) with failure producing a parallel, downward
      shift of the afterload (x) vs. cardiac output (y) relationship (P<0.01). Yet,
      afterload variation did not affect PRSW or ESPVR relationships in either normal
      or failing hearts (r2<0.12, P>0.05). CONCLUSION: Thus, the PRSW and ESPVR
      relationships are insensitive to acute afterload changes in both failing and
      normal hearts, and the failing left ventricle is no more afterload-sensitive than
      the normal heart.

PMID- 14675853
TI  - Improved regional left ventricular function after successful satellite cell
      grafting in rabbits with myocardial infarction.
AB  - OBJECTIVE: To evaluate whether satellite cells injected into infarct areas in
      rabbits remain viable during 6 weeks follow-up and can improve cardiac function
      as assessed by echocardiography. METHODS: Myocardial infarction was induced in 16
      New Zealand white rabbits, by ligation of the marginalis sinistra artery. Tissue
      from gluteus muscle biopsies was dissected into small pieces and cultured. Within
      2-3 weeks the cells were expanded by 2-3 orders of magnitude and were fluorescent
      labeled. Single cell pellets for resuspension at >10(6)/1 ml were directly
      injected into the infarct areas in 8 rabbits. In 8 additional rabbits, 1 ml
      saline was injected (control). Regional left ventricular function was assessed
      weekly by 2-D echocardiography until animals were sacrificed. Analysis was
      performed blind and independently by two experienced echocardiographers, based on
      the American Society of Echocardiography scheme. RESULTS AND DISCUSSION: Six
      treated and five control rabbits completed the study. One week after the artery
      occlusion, left ventricular function scoring did not differ between groups, mean
      8.7+/-1.6 vs 8.3+/-1.9 (P=0.74). At 6 weeks post-injection, echocardiographic
      score was significantly better in the treated group, mean 2.6+/-0.9 vs 6.9+/-2.1
      (P=0.002). The treated group showed significant gradual segmental improvement
      between the first week up to week 6. After sacrifice, macro and microscopic
      transmural areas showed typical changes of myocardial infarction. Histochemical
      staining identified viable grafted cells in high density 6 weeks post
      transplantation in all grafted hearts. CONCLUSION: Autologous satellite cells
      (skeletal myofiber), can be successfully grafted into rabbit hearts following
      myocardial infarction and may induce improved regional left ventricular function.

PMID- 14675854
TI  - Determinants of insulin sensitivity in chronic heart failure.
AB  - OBJECTIVE: To describe the determinants of insulin sensitivity (IS) in chronic
      heart failure (CHF), we created a model in which the influence of lifestyle
      factors and etiology of heart failure on IS were incorporated concomitantly with
      age, left ventricular ejection fraction (LVEF) and parameters of body
      composition. DESIGN: Observational cohort study. SETTING: Outpatient clinic for
      chronic heart failure. PATIENTS: Fifty-seven male CHF patients [NYHA class II
      III, age 61+/-9 years, body mass index (BMI) 26.9+/-3.3 kg/m2 (mean+/-S.D.)].
      INTERVENTIONS: Euglycemic hyperinsulinemic clamp, cycle ergometry, anthropometric
      measurements, LVEF and a physical activity questionnaire. MAIN OUTCOME MEASURES:
      A model explaining the variance of IS in CHF. RESULTS: IS was 18.2+/-8.6
      microg.kg(-1).min(-1).mU(-1).l(-1), fasting insulin level was 15.9+/-11.0 mU/l
      and fasting glucose level was 5.5+/-0.6 mmol/l. Peak VO2 was 19.1+/-4.9 ml.kg(
      1).min(-1) and LVEF 26.2+/-7.1%. IS was inversely associated with fasting insulin
      concentration (r=-0.50, P<0.001) and BMI (r=-0.54, P<0.001). After controlling
      for BMI, IS also revealed a correlation with age (r=-0.36, P<0.01). The model
      explained 60% of variance in IS: BMI contributed 20%, smoking 17%, age 17% and
      physical activity in daily life (DPA) 16% (all P<0.05) to the variance of IS,
      whereas LVEF (9%) and etiology of heart failure (8%) contributed moderately.
      CONCLUSIONS: In CHF patients, IS is for a major part predicted by BMI, smoking,
      age, daily physical activity, LVEF and etiology of heart failure.

PMID- 14675855
TI  - Screening for left ventricular dysfunction using a hand-carried cardiac
      ultrasound device.
AB  - BACKGROUND: The hand-carried cardiac ultrasound (HCU) device is a recently
      introduced imaging device, which may be potentially useful in the primary care
      setting. AIM: To test the screening potential of a HCU for the detection of left
      ventricular (LV) dysfunction by evaluating LV ejection fraction (LVEF) and
      inferior vena cava (IVC) collapse. Standard echocardiographic system (SE) and
      plasma brain natriuretic peptide (BNP) measurements were used as a reference.
      METHODS: Eighty-eight consecutive patients (56 male, aged 59+/-12 years) with
      suspected LV dysfunction were enrolled in the study. The HCU-LVEF was visually
      estimated and the SE-LVEF was derived by the Simpson's biplane method. A LVEF
      <40% represented LV dysfunction. An IVC collapse of <50% and BNP levels > or =15
      pmol/l were considered abnormal. The correlation of HCU-LVEF, HCU-IVC and BNP to
      the SE-LVEF and SE-IVC was analysed independently using 2x2 tables. RESULTS: Six
      patients were excluded because of poor echo images. 19/82 patients had LV
      dysfunction. The HCU and BNP could identify 17 and 18 out of these 19 patients,
      respectively. The agreement for LVEF and IVC collapse between SE and HCU was 96%
      for both parameters. The sensitivity of IVC collapse, HCU-LVEF and BNP in
      identifying patients with LV dysfunction was 26, 89 and 94%, respectively.
      CONCLUSION: A HCU device can reliably be used as a screening tool for LV
      dysfunction.

PMID- 14675856
TI  - Identification of previously undiagnosed left ventricular systolic dysfunction:
      community screening using natriuretic peptides and electrocardiography.
AB  - AIMS: We examined strategies to improve the positive predictive value of
      natriuretic peptides in screening for undiagnosed left ventricular systolic
      dysfunction (LVSD) in the community. METHODS AND RESULTS: The value of B
      type(BNP), N-terminal proB-type (N-BNP) and N-terminal proAtrial(N-ANP)
      natriuretic peptides was prospectively assessed in 1360 subjects (45-80 years)
      together with echocardiography and electrocardiography. Seventeen individuals had
      definite and 13 had borderline, LVSD. Receiver-operating-characteristic (ROC)
      curve analysis showed the superiority of BNP (ROC areas 0.942 for definite LVSD,
      P<0.03; 0.934 for borderline LVSD, P<0.003) compared to N-BNP or N-ANP. Peptide
      levels, major ECG abnormality and ischaemic heart disease (IHD) history were
      independent predictors of LVSD. Logistic regression modelling incorporating these
      factors improved ROC areas for all natriuretic peptides. The specificity of all
      natriuretic peptides is enhanced by consideration of these factors. CONCLUSIONS:
      In population screening for definite LVSD, consideration of plasma natriuretic
      peptide levels together with the presence of major ECG abnormalities and IHD
      history reduces by a factor of six (in comparison to consideration of plasma
      natriuretic peptide levels in isolation) the number of subjects requiring
      echocardiography to detect one case of LVSD (for BNP, 44 falling to seven).
      Similar improvements were evident for N-ANP and N-BNP. Inclusion of major ECG
      abnormalities and IHD history improves the performance of any natriuretic peptide
      used in screening programmes for ruling in undiagnosed LVSD.

PMID- 14675857
TI  - Instruments to measure acceptability of information and acquisition of knowledge
      in patients with heart failure.
AB  - BACKGROUND: Patients with heart failure suffer from poor health outcomes and
      require combinations of medications to treat their disease. Providing patients
      with knowledge through education is one mechanism to help them improve compliance
      with complicated treatment regimens. METHODS: We developed and tested two
      instruments. The first instrument, which we call the measure of educational
      material acceptability (EMA), was designed to help us differentiate between
      written educational materials according to patients' subjective responses. The
      second instrument, the knowledge acquisition questionnaire (KAQ), which measures
      knowledge gained, was designed to determine whether patients understand the
      rationale and mechanics of their heart failure management. We explored the
      measurement properties of both instruments. RESULTS: The internal consistency of
      the EMA was 0.79 (Cronbach's alpha). The internal consistency of the KAQ was 0.61
      and its responsiveness, measured using change scores of knowledge before and
      after an educational intervention, was 0.75. CONCLUSIONS: We have developed
      instruments that measure acceptability and knowledge acquisition, and that
      clinicians and investigators involved in heart failure programs may find useful
      in developing educational material and measuring the impact of their
      interventions on patients' knowledge.

PMID- 14675858
TI  - Torasemide vs. furosemide in primary care patients with chronic heart failure
      NYHA II to IV--efficacy and quality of life.
AB  - BACKGROUND: The hypothesis was that torasemide, due to more predictable
      pharmacokinetics/pharmacodynamics, induces greater improvements in functional and
      social limitation than furosemide and reduces the frequency of hospitalisations
      in primary care patients with chronic heart failure (CHF). PATIENTS AND METHODS:
      Prospective, randomized, unblinded study in primary care, 237 patients with CHF
      (NYHA II-IV), all on ACE inhibitors. Randomisation: torasemide (n=122) or
      furosemide (n=115), treated for 9 months. ENDPOINTS: Clinical efficacy, quality
      of life, safety, tolerability, hospitalisations. RESULTS: Clinical improvement
      was observed in both groups, but the trend to improve by at least one NYHA class
      was significant only in torasemide- (P=0.014), but not in furosemide-treated
      patients. There were no differences with regard to adverse events and
      hospitalisation due to CHF. Overall, tolerability (P=0.0001) and improvement in
      daily restrictions (P=0.0002) were significantly higher, number of mictions at 3,
      6 and 12 h after diuretic intake (P<0.001 at all time points) and urgency to
      urinate (P<0.0001) significantly lower in torasemide- vs. furosemide-treated
      patients. CONCLUSION: CHF patients treated with torasemide gain a higher benefit
      in quality of life than furosemide treated patients, due to torasemide's dual
      effect on both clinical status and social function.

PMID- 14675859
TI  - Efficacy and tolerability of the long-term administration of carvedilol in
      patients with chronic heart failure with and without concomitant diabetes
      mellitus.
AB  - BACKGROUND: Diabetes is frequently associated with heart failure and is an
      independent risk factor for an increased mortality and morbidity. Beta-blockers
      are traditionally regarded as relatively contraindicated in patients with
      diabetes mellitus. AIM OF THE STUDY: To assess the efficacy and tolerability of
      carvedilol administration in patients with heart failure and concomitant
      diabetes. METHODS AND RESULTS: One hundred ninety-three patients (68 diabetics,
      125 non-diabetics) with chronic heart failure were assessed by radionuclide
      ventriculography, cardiopulmonary exercise testing and right heart
      catheterization before and after 12 months of maintenance carvedilol treatment
      (mean dose, 40+/-19 mg daily). Diabetic patients were older and with a lower peak
      VO2, compared with non-diabetics. Long-term carvedilol administration was
      associated with an improvement in left ventricular function, clinical symptoms,
      resting and exercise hemodynamic parameters compared to baseline, with no
      significant difference between the diabetic and the non-diabetic patients. The
      incidence of adverse effects was also similar between the two groups. Diabetics
      had higher all-cause mortality with a similar mortality and hospitalization rate,
      compared to non-diabetics during 33+/-20 months of follow-up. CONCLUSION:
      Concomitant diabetes does not influence the efficacy and tolerability of
      carvedilol administration in patients with chronic heart failure.

PMID- 14675860
TI  - Congestive heart failure with preserved left ventricular systolic function after
      acute myocardial infarction: clinical and prognostic implications.
AB  - AIMS: To characterise the prevalence, in-hospital complications, management, and
      long-term outcome of patients with congestive heart failure but preserved left
      ventricular systolic function after acute myocardial infarction. METHODS: 3166
      consecutive patients screened for entry in the Bucindolol Evaluation in Acute
      Myocardial Infarction Trial with definite acute myocardial infarction and
      echocardiographic assessment of left ventricular systolic function were included
      between 1998 and 1999 in this prospective observational study. Main outcome
      measures were occurrences of in-hospital complications and all cause mortality.
      RESULTS: Congestive heart failure was seen during hospitalisation in 1464
      patients (46%), 717 patients had preserved left ventricular systolic function
      (wall motion index > or =1.3 corresponding to ejection fraction > or =0.40), and
      732 patients had systolic dysfunction (wall motion index <1.3). One year
      mortality in patients with no heart failure, heart failure with preserved
      systolic function, and heart failure with systolic dysfunction were 6, 22 and
      35%, P<0.0001. Unadjusted risk of death from all causes associated with heart
      failure and preserved systolic function was 3.3 (95% CI 2.8-4.0), and after
      adjustment for baseline characteristics and left ventricular systolic function in
      multivariate Cox proportional hazards analysis the risk was 2.1 (95% CI 1.7-2.6),
      P<0.0001. CONCLUSIONS: Congestive heart failure is frequently present in patients
      with preserved left ventricular systolic function, and is associated with
      increased risk of in-hospital complications and death following acute myocardial
      infarction.

PMID- 14675861
TI  - Apical left ventricular aneurysm without atrio-ventricular block due to a lamin
      A/C gene mutation.
AB  - BACKGROUND: Mutations in LMNA gene encoding two ubiquitously expressed nuclear
      proteins, lamins A and C, give rise to up to 7 different pathologies affecting
      specific tissues. Three of these disorders affect cardiac and/or skeletal muscles
      with atrio-ventricular conduction disturbances, dilated cardiomyopathy and sudden
      cardiac death as common features. RESULTS: A new LMNA mutation (1621C>T, R541C)
      was found in two members of a French family with a history of ventricular rhythm
      disturbances and an uncommon form of systolic left ventricle dysfunction. The two
      patients: the proband and his daughter, were affected and exhibited an atypical
      form of dilated cardiomyopathy with an unexplained left ventricle aneurysm
      revealed by ventricular rhythm disturbances without atrio-ventricular block.
      CONCLUSION: This finding reinforces the highly variable phenotypic expression of
      LMNA mutation and emphasizes the fact that LMNA mutations can be associated with
      different cardiac phenotypes.

PMID- 14675862
TI  - Regional virus laboratory Kelvin buildings.

PMID- 14675863
TI  - A role for arrays in clinical virology: fact or fiction?
AB  - Microarrays of DNA probes have at least three roles in clinical virology. These
      are: firstly, in diagnosis, to recognise the causative agent of an illness;
      secondly, for molecular typing for (i) patient management, (ii) epidemiological
      reasons (e.g. investigating routes of transmission), (iii) purposes related to
      vaccine use; and thirdly, in research, to investigate the interactions between
      the virus and the host cell. Microarrays intended for syndromic diagnostic
      purposes require genome specific probes to capture the unknown target viral
      sequences and thereby reveal the presence of that virus in a test sample.
      Microarrays intended for typing and patient management, e.g. monitoring antiviral
      drug resistant mutations require a set of probes representing the important
      sequence variants of one or more viral genes. Microarrays intended for research
      into virus-host interactions require probes representative of each individual
      gene or mRNA of either the virus or the host genome. Diagnostic microarrays are
      dependent for their utility and versatility on generic, multiplex or random
      polymerase chain reactions that will amplify any of several (unknown) viral
      target sequences from a patient sample. In this review, the existing and
      potential applications of microarrays in virology, and the problems that need to
      be overcome for future success, are discussed.

PMID- 14675864
TI  - Severe acute respiratory syndrome (SARS)--paradigm of an emerging viral
      infection.
AB  - An acute and often severe respiratory illness emerged in southern China in late
      2002 and rapidly spread to different areas of the Far East as well as several
      countries around the globe. When the outbreak of this apparently novel infectious
      disease termed severe acute respiratory syndrome (SARS) came to an end in July
      2003, it had caused over 8000 probable cases worldwide and more than 700 deaths.
      Starting in March 2003, the World Health Organization (WHO) organised an
      unprecedented international effort by leading laboratories working together to
      find the causative agent. Little more than one week later, three research groups
      from this WHO-coordinated network simultaneously found evidence of a hitherto
      unknown coronavirus in SARS patients, using different approaches. After Koch's
      postulates had been fulfilled, WHO officially declared on 16 April 2003 that this
      virus never before seen in humans is the cause of SARS. Ever since, progress
      around SARS-associated coronavirus (SARS-CoV) has been swift. Within weeks of the
      first isolate being obtained, its complete genome was sequenced. Diagnostic tests
      based on the detection of SARS-CoV RNA were developed and made available freely
      and widely; nevertheless the SARS case definition still remains based on clinical
      and epidemiological criteria. The agent's environmental stability, methods
      suitable for inactivation and disinfection, and potential antiviral compounds
      have been studied, and development of vaccines and immunotherapeutics is ongoing.
      Despite its grave consequences in humanitarian, political and economic terms,
      SARS may serve as an example of how much can be achieved through a well
      coordinated international approach, combining the latest technological advances
      of molecular virology with more "traditional" techniques carried out to an
      excellent standard.

PMID- 14675865
TI  - Severe influenza infection in a chronic hepatitis C carrier: failure of
      protective serum HI antibodies after IM vaccination.
AB  - BACKGROUND: Influenza is an important cause of morbidity and mortality in
      immunocompromised hosts. Recommendations exists for vaccination each year, yet
      disease can still occur. OBJECTIVES: To describe the course of fulminant
      influenza infection in a patient with HCV. STUDY DESIGN: Case study in which
      correlation was made between immunoglobulin response to influenza vaccination to
      the disease and its unique clinical course caused by influenza virus. RESULTS:
      Influenza A/Jerusalem 17/98 (H(1)N(1)) was isolated from the throat of a chronic
      hepatitis C carrier who, presented with shortness of breath, and subsequent
      massive bilateral pneumonia. The patient was previously immunized IM with
      inactive influenza vaccine. He developed protective levels of humoral antibodies
      (1:80 hemagglutination inhibition (HI) antibodies) against the three strains of
      the vaccine that evidently did not prevent respiratory infection. The development
      of massive bilateral pneumonia and continued presence of influenza virus in the
      respiratory tract may have been due to his underlying medical condition and
      possible lack of mucosal secretory IgA (SIgA) antibodies. CONCLUSION: We have
      presented a case of prolonged influenza infection post vaccination. This case
      emphasizes the importance of an improved vaccine that would stimulate a better
      immunologic response, especially in immunocompromised patients.

PMID- 14675866
TI  - Unusual codon 69 insertions: influence on human immunodeficiency virus type 1
      reverse transcriptase drug susceptibility.
AB  - INTRODUCTION: Multiple amino acid changes in the reverse transcriptase (RT)
      enzyme of the human immunodeficiency virus 1 (HIV-1) confer simultaneous
      resistance to most nucleoside RT inhibitors (NRTI). It may take place through
      different pathways: one of these is the codon 69 insertion, which can involve
      several 2-amino acid patterns. MATERIALS AND METHODS: We are reporting the case
      of three patients treated with various antiretroviral compounds. For these
      subjects we have conducted both a genotypical and a phenotypical analysis in
      order to understand what kind of influence these insertions may have on HIV-1 RT
      drug susceptibility. Plasma samples from these patients have been extracted and
      the RT region has been amplified, cloned and sequenced; meanwhile their PBMCs
      have been separated, cultivated and then tested for drug susceptibility. RESULTS:
      Data obtained from the cloning assay showed that the patients had different
      mutational patterns but constant multiple resistance to NRTI. In particular, they
      harbored mutations related to Zidovudine (ZDV), 3TC and various NRTIs. Moreover,
      all three samples had a T69S substitution followed by three different dual amino
      acid insertions: SG, TG and VG. Several phenotypic experiments revealed that the
      viruses were resistant to 3TC as well as to ZDV and ABC. Different results were
      obtained using d4T and ddI. DISCUSSION: In our three patients, all mutation
      inserts impaired the use of NRTI, particularly ZDV and 3TC. Patient 001 presented
      a pattern that should not cause a high phenotypic resistance to 3TC per se, and
      so we can argue that the concomitant presence of the insertion T69S (SG) makes
      this isolate moderately resistant to this drug. We observed a similar phenomenon
      in subject 003. d4T was less involved in the resistance generation caused by the
      RT insertion (in one out of three cases). Moreover, we identified a new 2aa
      insertion (TG) that has, to the best of our knowledge, never been reported
      before. A careful survey of novel RT genotypic insertion is thus warranted.

PMID- 14675867
TI  - Enumeration of latently infected CD4+ T cells from HIV-1-infected patients using
      an HIV-1 antigen ELISPOT assay.
AB  - BACKGROUND: Latently infected resting CD4(+) T cells carrying replication
      competent HIV-1 are present in naive, chronically infected individuals as well as
      in those who are receiving highly active antiretroviral therapy (HAART). These
      cells serve as a potential source of reactivation of viral replication and remain
      a major obstacle for the eradication of HIV-1. OBJECTIVES: The enzyme-linked
      immunospot (ELISPOT) assay was adapted to the detection and the enumeration of
      HIV-1 antigen-secreting cells at the single cell level. We applied this test to
      count latently HIV-1-infected CD4(+) T cells. STUDY DESIGN: Latently infected
      CD4(+) T cells were assessed in an in vitro model of HIV-1-infected resting
      CD4(+) T cells as well as in eighteen HAART-treated and in four HIV-1-infected
      untreated patients. Enriched CD4(+) T cells were cultured with or without
      antibodies against CD3 and CD28 T cell receptors and with irradiated peripheral
      blood mononuclear cells from HIV-1 seronegative individuals. At the term of the
      cell culture, CD4(+) T lymphocytes were tested using the HIV-1 antigen ELISPOT
      assay. RESULTS: In the experimental HIV-1 infection model, 5579+/-4190 CD4(+) T
      cells secreting HIV-1 antigen were enumerated after polyclonal activation. In
      contrast, only 15+/-6 HIV-1 immunospots were obtained from unstimulated T cells.
      In all patients tested, induced HIV-1 antigen-secreting cells were measured at a
      frequency of 55+/-108/10(6) CD4(+) T cells. CONCLUSION: As each immunospot
      represents one HIV-1 antigen-secreting cell, the HIV-1 ELISPOT assay is a
      powerful to enumerate circulating CD4(+) T lymphocytes latently infected with HIV
      1.

PMID- 14675868
TI  - A multiplex-PCR to identify hepatitis B virus--enotypes A-F.
AB  - Eight genotypes (A-H) of hepatitis B virus (HBV) are known with variations in
      nucleotide sequences greater than 8%. Several recent publications found that the
      clinical course and outcome of antiviral therapy depended on the genotype of the
      infecting HBV strain. Large epidemiological studies will require the availability
      of a system which is rapid, reliable and can be performed on a large number of
      samples. We have developed a multiplex-PCR assay which uses genotype-specific
      primer pairs for HBV genotypes A-F. These primer pairs specifically amplified HBV
      DNA of the respective genotype, either in single or in multiplex-PCR. Sensitivity
      of the assay was in the range of 10(4) genome equivalents.

PMID- 14675869
TI  - Serum L-lactate and pyruvate in HIV-infected patients with and without presumed
      NRTI-related adverse events compared to healthy volunteers.
AB  - BACKGROUND: Nucleoside reverse transcriptase inhibitors (NRTIs) used in
      antiretroviral therapy may cause mitochondrial toxicity. Mitochondrial
      dysfunction leads to disturbance of the glucose metabolism, resulting in an
      accumulation of L-lactate (L) and pyruvate (P), with an enhanced L/P ratio.
      OBJECTIVES: We analysed lactate and pyruvate blood samples of patients of our
      outpatient department. Aim of the analysis was to detect preliminary
      mitochondrial toxicity in patients on antiretroviral nucleoside analogues, which
      might result in disturbances of L, P, L/P ratio, bicarbonate (Bic) or beta
      hydroxybutyrate/aceto-acetate (beta-HB/AA) ratios. STUDY DESIGN: Blood samples of
      L, P, Bic, beta-HB and AA were analysed in four groups of subjects. The first
      group (A) consisted of patients with presumed NRTI-related adverse events (n=21),
      the second group (B) consisted of patients without adverse events (n=28), the
      third group (C) were HIV-infected patients without antiretroviral therapy (n=6)
      and the last group (D) were healthy controls (n=12). The mean duration of NRTI
      treatment was 18 months (range 0-78 months). RESULTS: The mean lactate level in
      group A was 2319 micromol/l (S.D. +/-1231, median 1741 micromol/l), in group B
      1257 micromol/l (S.D. +/-607, median 1087), Group C 1285 (S.D. +/-451, median
      1245 micromol/l) and 951 micromol/l (S.D. +/-270, median 979) in the healthy
      controls. No significant differences in pyruvate, L/P, Bic and beta-HB/AA were
      seen in the four groups. The mean lactate level in patients on stavudine was 1980
      micromol/l (S.D. +/-1197) versus 1051 micromol/l (S.D. +/-395, P=0.01) in
      patients on zidovudine. All patients with lactate values above 2700 micromol/l
      (eight) experienced adverse events. CONCLUSION: Lactate levels were higher in
      patients with presumed NRTI-related adverse events. Furthermore, HIV patients
      receiving a stavudine containing antiretroviral therapy had higher lactate values
      than patients without stavudine. Although routine lactate measurement in all
      patients on antiretroviral therapy is not recommended, lactate measurement might
      be useful for follow up of patients with presumed NRTI-related adverse events and
      in patients with lactate levels above 2500 micromol/l. These patients require
      extra surveillance to evaluate if discontinuation of the current antiretroviral
      therapy is needed.

PMID- 14675870
TI  - Detection of parvovirus B19 IgG: choice of antigens and serological tests.
AB  - Serum samples were analysed for the presence of (a) IgG against VP1+VP2 using
      recombinant native conformational antigens by ELISA test (b) IgG against VP2
      using recombinant native conformational antigens by ELISA test and (c) IgG
      against VP1 and against VP2 using denatured linear antigens by Western blot. Out
      of the 446 samples examined, 353 were positive for specific B19 IgG and out of
      these, 98.6 % proved positive in the ELISA assay using conformational VP1+VP2
      antigens, 94.6% proved positive in the ELISA assay using conformational VP2
      antigens, 89.5% were positive at the Western blot assay using denatured linear
      VP1 and VP2 antigens, with all proving positive for linear VP1 and only 29.5% out
      of the positive samples proving positive for linear VP2. Since all samples
      positive by Western blot proved positive by ELISA, our data show that recombinant
      capsids obtained either with VP1+VP2 or with VP2 alone, used in ELISA, are very
      useful for detecting the immune response against both conformational and native
      linear epitopes of B19 structural proteins although some sera may have antibodies
      directed exclusively against VP1+VP2 antigens and few may have antibodies
      directed exclusively against VP2 antigens alone.

PMID- 14675871
TI  - An approach based on RFLP assay to investigate outbreaks of enteroviral
      meningitis.
AB  - BACKGROUND: Enteroviruses (EV) circulate worldwide and are a major cause for
      annual epidemics of meningitis in humans. During the last two decades, echovirus
      type 30 (E-30) has revealed to be one of the most prevalent enteroviruses at the
      origin of epidemics of EV meningitis. OBJECTIVES: To design an approach to timely
      investigate epidemics due to EV. To apply this strategy to the outbreak of
      meningitis due to E-30 that occurred at the end of year 2000 in Marseilles,
      France. STUDY DESIGN: The approach consisted to (i) determine whether the
      epidemic was caused by a dominant strain; (ii) identify the dominant strain by
      sequencing the first isolates during the outbreak; (iii) identify a restriction
      enzyme, capable to produce an Restriction fragment length polymorphism (RFLP)
      profile characteristic for the dominant strain, for rapid identification based on
      RFLP analysis of PCR products. RESULTS AND CONCLUSIONS: A total of 394 samples
      were tested; 258 (corresponding to 177 patients) were positive for the presence
      of EV by cell culture and/or RT-PCR. Sequence analysis of a 785-bp PCR product
      (including the 5' end of the VP1 gene) performed for the 30 first isolates
      permitted to identify a RFLP profile that was specific of the dominant strain
      after enzymatic cleavage by Bst X1. This RFLP profile was observed in 246 out of
      258 PCR products. This method of typing is rapid, simple and inexpensive, and may
      be applied for the epidemiological typing of EV in epidemic situations.

PMID- 14675873
TI  - Difficulties encountered with antiretroviral treatment and genotypic testing of
      HIV-1 drug resistance in the developing countries: the Tunisian experience (North
      Africa).

PMID- 14675872
TI  - Prevalence of hepatitis B virus DNA in anti-HBc-positive/HBsAg-negative sera
      correlates with HCV but not HIV serostatus.
AB  - BACKGROUND: Hepatitis B virus (HBV) DNA often remains detectable in serum despite
      clinical recovery and loss of HBsAg. OBJECTIVE: To study whether coinfection with
      HIV and HCV influence the chance of detecting HBV DNA in sera with markers of
      past hepatitis B. STUDY DESIGN AND RESULTS: The test panel included 160 anti-HBc
      positive/HBsAg-negative sera collected in the diagnostic setting. The following
      parameters were determined in the sera: anti-HIV (32% positive), anti-HCV (34%
      positive), HCV RNA (18% positive), and anti-HBs (37% positive). A highly
      sensitive PCR (90%-detection limit 100 copies/ml) amplifying the terminal protein
      (TP) region of HBV was established and HBV DNA was detected in 12.5% of the
      samples. In 70% of these samples, the HBV DNA concentration was below 500
      copies/ml as measured by real-time PCR in the S gene. Logistic regression
      analysis revealed that the chance of detecting HBV DNA was increased by a
      positive HCV serostatus (odds ratio 5.0, 95%-CI 1.6-15.7), whereas HIV
      coinfection (odds ratio 2.0, 95%-CI 0.7-5.8), anti-HBs (odds ratio 0.9, 95%-CI
      0.3-2.6), and HCV RNA status (odds ratio 0.4, 95%-CI 0.1-1.7) had no
      statistically significant influence. In contrast, the chance of detecting HCV RNA
      in the subgroup of anti-HCV-positive sera was increased by HIV coinfection (odds
      ratio 4.5, 95%-CI 1.2-17.4). Sequencing of the TP PCR products revealed neither a
      specific phylogenetic origin of the circulating HBV DNA nor clustering of
      uncommon mutations in the TP region. CONCLUSIONS: The prevalence of HBV DNA in
      serum of anti-HBc-positive/HBsAg-negative subjects correlates with HCV rather
      than HIV serostatus.

PMID- 14675874
TI  - [Meeting of Associate Editors, AKD and PREMISE].

PMID- 14675875
TI  - [Single clamp technique in elderly patients undergoing coronary artery surgery].
AB  - OBJECTIVE: The results of single clamp and partial clamp techniques were
      retrospectively compared in elderly patients (>70 years) undergoing coronary
      artery bypass grafting operation (CABG). METHODS: A total of 244 elderly patients
      undergoing CABG between January 1995 and March 2002 in our center were studied.
      Single-clamp technique was used in 32 cases (Group 1) and partial-clamp technique
      was used in 212 cases (Group 2). All patients had isolated coronary artery
      lesions and a primary elective coronary bypass grafting surgery was planned for
      every case. Preoperative, operative and postoperative variables; age, gender, pre
      and post-operative neurological status (stroke, amaurosis fugax, aphasia,
      hemiplegia, hemiparesis), cerebrovascular diseases, diabetes mellitus,
      hypertension, number of distal grafts, left ventricular score, durations of
      aortic cross-clamping and cardiopulmonary bypass (CPB) times, perfusion pressure
      during CPB, and postoperative cardiac status were recorded. Patients with a
      history of neurological complications were excluded from the study. RESULTS:
      Overall, mean age was 71.9+/-2.18 years. Patients in Group 1 were significantly
      older as compared to patients in Group 2 (p< 0.01). Average duration of cross
      clamping in Group 1 was significantly longer (p<0.001) compared to Group 2, but
      there were no differences with regard to the total duration of cardiopulmonary
      bypass (p=0.535). No patients had neurological complications in Group 1, however
      22 patients in Group 2 had neurological complications (p<0.05). CONCLUSION:
      Although single-clamp technique was associated with a longer cross-clamp time,
      the duration of CPB was not increased and the incidence of neurological
      complications was low.

PMID- 14675876
TI  - [Nightmare for cardiac surgeons: neurologic injury].

PMID- 14675877
TI  - Immunohistochemical and electron-microscopic characteristics of secretory
      cardiomyocytes in experimental myocardial infarction.
AB  - OBJECTIVE: To study immunohistochemical and electron-microscopic features of
      secretory cardiomyocytes in experimental myocardial infarction (MI). METHODS:
      Totally 15 hearts of dogs with experimental MI were studied. For electron
      microscopic study materials were collected from left atrium, and its several
      parts (appendix, lateral and frontal walls). For immunohistochemical analysis of
      atrial natriuretic factor (ANF) incubation in monoclone immune serum was used
      (standard monoclonal serum and primary mice antibodies, Immunon). For statistic
      processing we used Chi-square test (criterion of Pearson agreement). RESULTS:
      Immunohistochemical and electron-microscopic investigation after 24 hours from
      experimental myocardial infarction indicated increase of specific activity of
      secretory cardiomyocytes and after 48 hours decrease of secretion of ANF while
      cardiomyopathy appears. After 72 hours, blockade of ANF secretion with
      decompensation of secretory cardiomyocytes occurred. CONCLUSION:
      Imunohistochemical investigations and analysis of submicroscopic structures of
      secretory cardiomyocytes after experimental MI showed, that cells were
      functionally active 24 hours after myocardial infarction with further (48 hours
      and 72 hours of MI) decrease in amount and impairement of activity.

PMID- 14675878
TI  - Trimetazidine improves recovery during reperfusion in isolated rat hearts after
      prolonged ischemia.
AB  - OBJECTIVE: Trimetazidine (TMZ) is a cellular anti-ischemic agent, which has been
      studied in clinical and experimental investigations, and was shown to have
      protective affects against myocardial ischemia and reperfusion injury. The major
      objective of this study was to investigate the cardio-protective effects of
      trimetazidine in prolonged global ischemia subjected Langendorff perfused rat
      hearts. METHODS: Twenty rats (Male Sprague-Dawley) were divided into two study
      groups. In Group 2 (n=10) TMZ was given by intra-gastric gavage (3 mg/kg BW twice
      daily for 5 days) prior to operation and was added to the Krebbs-Henseleit
      perfusate to create a 10-6 M solution to perfuse the isolated rat hearts. Group 1
      (n=10) reserved as control group and received saline at the same time period. All
      hearts were paced at 300 beats/min. After a 20-minute of stabilization period,
      hearts in both groups were arrested for 120 minutes with crystalloid
      cardioplegia. After ischemic period, the hearts were then reperfused for 30
      minutes. Hemodynamic measurements from left ventricular latex balloon, coronary
      flow, and creatine kinase (CK-MB) and troponin T (cTnT) levels determined from
      the coronary effluent were analyzed at the end of stabilization and at every 10
      min intervals during reperfusion, and results were compared between two groups.
      RESULTS: No significant differences were observed in all entered hemodynamic and
      biochemical parameters between two groups at the end of the stabilization.
      However, peak systolic pressure, end diastolic pressure and +dP/dt values
      reflected improved mechanical myocardial recovery in Group 2 hearts after
      prolonged ischemia. Besides coronary flow measurements were higher in Group 2
      compared with Group 1. CK-MB and cTnT levels indicated to less enzymatic damage
      in trimetazidine treated hearts during reperfusion. CONCLUSION: In conclusion,
      both pre-treatment and treatment protocols with TMZ reduce the myocardial damage
      caused by global ischemia following reperfusion. We could speculate that this
      beneficial effect of trimetazidine might be useful in open-heart surgery
      patients, who were subjected to global myocardial ischemia.

PMID- 14675879
TI  - [The relationship between rhythm disturbances and incisions in adult sinus
      venosus atrial septal defects].
AB  - OBJECTIVE: Sinus venosus type atrial septal defects (SVASD) differ from the
      secundum atrial septal defects by its location and high incidence of combination
      with other cardiac anomalies, which inherently increases the risk of
      postoperative complications. Right atriotomy is the most preferred approach for
      repairing the SVASD. Postoperative sinus node dysfunction or other rhythm
      disturbances can be observed. We compared the postoperative complications between
      lateral cavatomy and right atriotomy in patients who had SVASD. METHODS: Twenty
      seven patients who had SVASD (of 384 total ASDs) associated with partial
      anomalous pulmonary venous connection (PAPVC) underwent surgical repair during
      the period of January 1992 - December 2001 in Gulhane Military Medical Academy.
      Sinus venosus type atrial septal defect was repaired through right atrial
      incision by routine bi-caval cannulation in 14 patients (Group 1) and repaired
      through lateral caval incision by direct caval cannulation in 13 patients (Group
      2). Lateral cavatomy was closed by pericardial patch in Group 2. We analyzed the
      relationship between incidence of rhythm disturbances and the technique in
      patients who had SVASD with or without partial anomalous pulmonary venous
      connection prospectively. RESULTS: All patients had a classical superior SVASD
      intraoperatively. Persistent left superior vena cava (PLSVC) was observed in 5
      patients (Group 1=3 patients, Group 2=2 patients). Postoperative mortality was
      seen in one patient in Group 1 due to pulmonary venous obstruction. In Group 1,
      one patient underwent re-operation for upper and middle lobectomy of the right
      lung. Ambulatory Holter monitorizations were done in all patients per 3 months
      periodically. In Group 1 sinus node dysfunction was observed in 4 patients and
      atrial fibrillation was observed in 2 patients, while in Group 2 only one patient
      had atrial fibrillation during follow-up period (p=0.037). CONCLUSION: Repair of
      SVASD in adult patients is associated with low operative mortality and morbidity.
      The closure of the defect by pericardial patch is the most preferred technique
      but obstruction of caval veins can be seen. We suggest that posterior cavatomy
      can be preferred to atriotomy because of low incidence of sinus node dysfunction
      and pulmonary or caval obstruction.

PMID- 14675881
TI  - [Factors regulating exercise capacity in heart failure and effects of Beta-
      receptor blockers on exercise tolerance].

PMID- 14675880
TI  - [Assessment of the efficacy of bisoprolol administration by cardiopulmonary
      exercise testing in patients with heart failure].
AB  - OBJECTIVE: It is well known that long-term therapy with beta-blockers reduces
      morbidity and mortality, improves left ventricular function in patients with
      heart failure. However the effect of beta-blockade on exercise tolerance in
      patients with heart failure remains unclear. In the present study we evaluated
      effects of the addition of bisoprolol to standart therapy with a diuretic and an
      angiotensin converting enzyme (ACE) inhibitor on exercise capacity in patients
      with chronic heart failure. METHODS: We enrolled 52 patients (mean age 59+/-11
      years) with stable, mild to moderate chronic heart failure and left ventricular
      ejection fraction of 40% or less receiving standart therapy with diuretic and ACE
      inhibitor. We randomly assigned patients to bisoprolol 1.25 mg (n=28) or control
      (n=24) groups. The drug progressively increased to a maximum dose of 5 mg per
      day. Cardiopulmonary exercise testing (CPET) was performed in all patients of the
      bisoprolol and control groups before and after 3 months from the beginning of the
      study. RESULTS: We found a significant increase in exercise duration, maximal O2
      uptake (pik VO2), the O2 uptake at the anaerobic threshold (VO2-AT) and O2-pulse
      (pik VO2/HR), and improved functional capacity (p<0.001). Bisoprolol produced
      significant reduction in heart rate at rest (p=0.01) and during maximal exercise
      (p=0.041). In the control group no significant changes were observed. CONCLUSION:
      The addition of bisoprolol to the standart therapy in patients with mild to
      moderate heart failure is well tolerated and improves functional capacity.

PMID- 14675882
TI  - [Echocardiographic evaluation of associated valve lesions in mitral stenosis].
AB  - OBJECTIVE: When mitral stenosis is associated with other valve lesions,
      diagnosis, prognosis and the treatment strategies are affected. Mitral valve
      prolapse may occur in some pathological settings that affect mitral apparatus. We
      investigated the incidence of valve lesions including mitral valve prolapse that
      accompany mitral stenosis and assessed the relation between echocardiographic
      measures. METHODS: Two hundred and one patients (31 male, 170 female) between 16
      and 72 years of age (mean age 40.9+/-11.4 years) with mitral stenosis were
      included in the study. Patients were divided into three groups according to the
      mitral valve area obtained by echocardiography using planimetric method as Group
      I (MVA<1.1 cm(2)), Group II (MVA -1.1-1.5 cm(2)) and Group III (MVA >1.5 cm2).
      RESULTS: Mitral stenosis with mitral regurgitation, aortic regurgitation, aortic
      stenosis, combined aortic valve disease, tricuspid regurgitation and tricuspid
      stenosis were found in 117 (58.2%), 84 (41.8%), 18 (9%), 9 (4.5%), 62 (30.8%) and
      6 (3%) patients, respectively. Twenty- three patients (11.4%) had mitral valve
      prolapse in only anterior leaflet. Nobody of patients had mitral valve prolapse
      of posterior mitral valve leaflet. Age, gender, rhythm, degree of stenosis,
      degree of mitral and aortic regurgitations, mean pressure gradient, left atrial
      diameter, ejection fraction and valve score did not differ in patients with and
      without mitral valve prolapse. CONCLUSION: Our study has shown that valve lesions
      including mitral valve prolapse frequently accompany mitral stenosis and the
      incidence of mitral valve prolapse in patients with mitral stenosis is high.

PMID- 14675883
TI  - [Is frequency of mitral valve prolapse increased in mitral stenosis cases?].

PMID- 14675884
TI  - Effect of statin therapy added to ACE-inhibitors on blood pressure control and
      endothelial functions in normolipidemic hypertensive patients.
AB  - OBJECTIVE: Endothelium-dependent vasodilatation is impaired in hypertension.
      Statins have been shown to improve endothelial functions in hyperlipidemic
      subjects. We aimed to investigate the effect of statins on endothelium-dependent
      flow mediated dilatation (FMD) and blood pressure (BP) in normocholesterolemic
      hypertensive patients. METHODS: This randomized prospective study consisted of 56
      patients with newly diagnosed essential hypertension. All patients received
      angiotensin converting enzyme (ACE) inhibitor lisinopril (5 mg/day) as
      antihypertensive therapy, and half of them were randomized to
      simvastatin(20mg/day) irrespective of serum lipid levels. All subjects underwent
      brachial artery ultrasonographic examination for the measurement of FMD before
      randomization and at the end of 12 weeks treatment. RESULTS: A total of 39
      patients completed the study (21 patients in the statin + ACE inhibitor group,
      and 18 patients in the ACE-inhibitor alone group). Blood pressure levels were
      substantially reduced in both groups after treatment. In statin+ ACE-inhibitor
      group systolic pressure reduced by 23% (p=0.0001) and diastolic BP reduced by 23%
      (p=0.0001). In ACE-inhibitor alone group these ratios were 20% (p=0.001) and 21%
      (p=0.001), respectively. Meanwhile, pulse pressure (PP) decreased by 25% in
      statin+ ACE-inhibitor group (P=0.0001) and by 16% in ACE inhibitor-alone group
      (p=0.0051). Baseline FMD was significantly impaired in overall patients with
      hypertension as compared with healthy controls (13+/-8 vs. 24+/-8 %, P = 0.001).
      After treatment FMD decreased by 23% in lisinopril alone group (p=0.054). There
      were no correlations between FMD improvement, LDL reduction, BP or PP changes in
      both groups. CONCLUSION: Addition of simvastatin to ACE-inhibitor treatment in
      newly diagnosed hypertensive patients with normal cholesterol levels,
      significantly reduced PP and facilitated BP control, but did not affect
      endothelium-dependent dilatation. Further long-term large scale studies are
      needed to clarify the effect of various statins on endothelial functions of
      either hypercholesterolemic or normocholesterolemic hypertensive patients.

PMID- 14675885
TI  - Comparing two different therapies.

PMID- 14675886
TI  - [New horizons in cardiovascular treatment: cellular cardiomyoplasty and stem cell
      transplantation].
AB  - Today, congestive heart failure and acute myocardial infarction, which is
      accepted as the main factor that contributes to the development of heart failure,
      are major causes of deaths despite advances in surgical procedures, mechanical
      assistance devices, drug therapy and organ transplantation. However, these
      procedures only prevent further myocardial deterioration and do not act on the
      underlying pathophysiology which are fibrosis and cardiac remodeling. As further
      advances in genetics provide the possibility of preventing fibrosis and
      cardiomyocyte regeneration in damaged myocardium, studies are being made in this
      way. For this reason, a variety of cell types including stem cells were used and
      successful results were obtained. After studies on animal models; pilot studies
      to explore the effect of cellular cardiomyoplasty and stem cell implantation on
      humans have been started. Data that have been gained from human studies till now
      are encouraging for further studies in this era. But there is a need for larger
      scale randomized trials to determine the post-transplantation risk, as well as
      long-term safety and efficacy.

PMID- 14675887
TI  - [Nonatherosclerotic causes of coronary artery disease].

PMID- 14675888
TI  - [Atrioventricular complete heart block developed due to verapamil use together
      with honey consumption].

PMID- 14675889
TI  - [Endovascular treatment of acute type B aortic dissection: a case report].

PMID- 14675890
TI  - [Endovascular treatment of acute aortic dissections].

PMID- 14675891
TI  - [Bilateral coronary artery fistulas].

PMID- 14675892
TI  - [A case of myocardial infarction developed after paint thinner exposure].

PMID- 14675893
TI  - Workshop on secondary prevention of myocardial infarction and stroke and
      management of cardiovascular risk.

PMID- 14675894
TI  - The VII World Congress of Echocardiography and Vascular Ultrasound, Buenos Aires,
      Argentina, October 10th-12th, 2003.

PMID- 14675895
TI  - Pulmonary vascular sling with aberrant right upper lobe pulmonary artery in a
      child.

PMID- 14675896
TI  - [Isolated ventricular noncompaction (spongy myocardium): angiographic diagnosis].

PMID- 14675897
TI  - A chronic pseudoaneurysm with organized thrombus at the basal and mid segments of
      posterolateral wall of the left ventricle.

PMID- 14675898
TI  - Rare complication of aortic valve replacement: aorto-right atrial fistula.

PMID- 14675899
TI  - [Tricuspid valve endocarditis mimicking cardiac tumor].

PMID- 14675900
TI  - [Mortal complication of mitral stenosis: floating thrombus in the left atrium].

PMID- 14675901
TI  - NADPH-cytochrome P-450 reductase is involved in flunitrazepam reductive
      metabolism in Hep G2 and Hep 3B cells.
AB  - Flunitrazepam (FNTZ), like other benzodiazepines, has a high affinity for the
      benzodiazepine receptor within the gama-aminobutyric acid (GABA) complex. These
      affinities correlate with the pharmacological and therapeutic potencies of the
      drug. FNTZ is a drug commonly abused by young adults. In humans, FNTZ is oxidized
      to the major metabolites N-demethylflunitrazepam (DM FNTZ) and 3
      hydroxyflunitrazepam (3-OH FNTZ) and reduced to 7-aminoflunitrazepam (7A FNTZ).
      Human CYP2C19 and CYP3A4 are the principal P-450 cytochromes involved in DM FNTZ
      and 3-OH FNTZ formation. However, it is not clear which enzyme is responsible for
      the reduction of FNTZ to 7-aminoflunitrazepam (7A FNTZ). In this study, the
      involvement of NADPH-cytochrome P-450 reductase in the conversion of FNTZ to 7A
      FNTZ was investigated in two human hepatoma cell lines, human lymphoblast
      microsomes specifically expressing human NADPH-cytochrome P-450 reductase and
      purified recombinant human HADPH-cytochrome P-450 reductase. Significantly more
      FNTZ was converted to 7A FNTZ in Hep G2 than in Hep 3B cells, and this difference
      was associated with the catalytic activity and protein levels of NADPH-cytochrome
      P-450 reductase in these cells. In Hep G2 cells, conversion of FNTZ to 7A FNTZ
      was effectively inhibited by alpha-lipoic acid, an NADPH-cytochrome P-450
      reductase inhibitor. In addition, formation of 7A FNTZ by the microsomal fraction
      of Hep G2 cells was specifically inhibited by antibody against NADPH-cytochrome P
      450 reductase. Under hypoxia (N2 85%; CO2 5%; H2 10%), human lymphoblast
      microsomes specifically expressing human NADPH-cytochrome P-450 reductase and
      purified recombinant human NADPH-P-450 reductase catabolized FNTZ to 7A FNTZ in a
      concentration-dependent manner. These results suggest that NADPH-cytochrome P-450
      reductase is involved in the reductive metabolism of FNTZ to 7A FNTZ under
      hypoxic conditions.

PMID- 14675902
TI  - Enhanced pulmonary inflammatory response to inhaled endotoxin in pregnant rats.
AB  - Evidence suggests that pregnant animals are more sensitive than nonpregnant
      animals to the systemic administration of endotoxin. Studies were undertaken to
      assess whether an enhanced sensitivity of the pulmonary system to aerosolized
      endotoxin might exist during pregnancy. Pregnant Sprague-Dawley female rats (17 d
      of gestation) or age-matched virgin female rats were exposed to air or endotoxin
      (lipopolysaccharide) by inhalation for 3 h. At 18 h following exposure to
      endotoxin, lactate dehydrogenase activity levels in bronchoalveolar lavage (BAL)
      fluid samples from pregnant rats were 1.5-fold greater than those from endotoxin
      exposed virgin rats. BAL polymorphonuclear leukocyte (PMN) numbers were also
      approximately twofold greater in pregnant rats than in virgins following the
      inhalation of endotoxin. The increases in BAL PMNs in pregnant rats following
      endotoxin exposure were observed just following exposure to endotoxin as well as
      at 18 h following exposure. These results indicate that an increased pulmonary
      inflammatory response to inhaled endotoxin occurs during pregnancy in rats.
      Additional findings suggest that these pregnancy-linked pulmonary responses to
      endotoxin cannot be explained by the following potential mechanisms: changes in
      the inhaled dose of endotoxin, or alterations in the responsiveness of alveolar
      macrophages to endotoxin. To our knowledge this is the first study that has
      evaluated pulmonary responses to inhaled endotoxin during pregnancy. Our finding
      that pregnancy is associated with an increased lung inflammatory response to
      aerosolized endotoxin raises the possibility that there may be a generalized
      enhancement of pulmonary responses to inhaled toxic agents during pregnancy.

PMID- 14675903
TI  - Metabolism and toxicity of the styrene metabolite 4-vinylphenol in CYP2E1
      knockout mice.
AB  - 4-vinylphenol (4-VP) is a minor metabolite of styrene and is several times more
      potent as a hepatotoxicant and pneumotoxicant than is either the parent compound
      or the major metabolite of styrene, styrene oxide. 4-VP is metabolized primarily
      by CYP2E1 and CYP2F2. To further elucidate the possible role of 4-VP in styrene
      induced toxicity and the importance of its metabolism by CYP2E1, the metabolism
      of 4-VP and its hepatotoxicity and pneumotoxicity were compared in wild-type and
      CYP2E1 knockout mice. There were no marked differences between the wild-type and
      knockout mice in the rates of microsomal metabolism of 4-VP in either liver or
      lung. This unexpected result mimics previous findings with styrene metabolism in
      wild-type and knockout mice. When mice were administered 100 mg/kg 4-VP ip, the
      knockout mice were more susceptible to hepatotoxicity, as measured by increases
      in serum sorbitol dehydrogenase activity, than were the wild-type mice. There was
      no significant difference in the pneumotoxicity between the two strains. The data
      suggest that, as for styrene, additional cytochromes P-450 are involved in the
      metabolism of 4-VP.

PMID- 14675904
TI  - Effects of chronic alcohol consumption on dermal penetration of pesticides in
      rats.
AB  - Topically applied ethanol is a well-known dermal penetration enhancer. The
      purpose of this work was to determine if ethanol consumption might also increase
      transdermal penetration. Male rats were fed either an ethanol containing or
      control diet for 6-8 wk. After the feeding regime was completed, skin was removed
      and placed in an in vitro diffusion system. The transdermal absorption of four
      very commonly used herbicides was determined. Penetration through skin from
      ethanol-fed rats was enhanced when compared to control by a factor of 5.3 for
      paraquat, 2.4 for atrazine, and 2.2 for 2,4-dichlorophenoxyacetic acid (2,4-D),
      and reduced by a factor 0.6 for trifluralin. Comparison of physical factors of
      the herbicides to the penetration enhancement revealed an inverse linear
      correlation with lipophilicity, as defined by log octanol/water partition
      coefficient (log Kow) with r2 =.98. These changes were at least partially
      reversible after 1 wk of abstinence from ethanol. These experiments demonstrate
      that regular ethanol consumption can alter the properties of the dermal barrier,
      leading to increased absorption of some chemicals through rat skin. If ethanol
      consumption has the same effect on human skin it could potentially have adverse
      health effects on people regularly exposed to agricultural, environmental, and
      industrial chemicals.

PMID- 14675905
TI  - Stress and combined exposure to low doses of pyridostigmine bromide, DEET, and
      permethrin produce neurochemical and neuropathological alterations in cerebral
      cortex, hippocampus, and cerebellum.
AB  - Exposure to a combination of stress and low doses of the chemicals pyridostigmine
      bromide (PB), DEET, and permethrin in adult rats, a model of Gulf War exposure,
      produces blood-brain barrier (BBB) disruption and neuronal cell death in the
      cingulate cortex, dentate gyrus, thalamus, and hypothalamus. In this study,
      neuropathological alterations in other areas of the brain where no apparent BBB
      disruption was observed was studied following such exposure. Animals exposed to
      both stress and chemical exhibited decreased brain acetylcholinesterase (AChE)
      activity in the midbrain, brainstem, and cerebellum and decreased m2 muscarinic
      acetylcholine (ACh) receptor ligand binding in the midbrain and cerebellum. These
      alterations were associated with significant neuronal cell death, reduced
      microtubule-associated protein (MAP-2) expression, and increased glial fibrillary
      acidic protein (GFAP) expression in the cerebral cortex and the hippocampal
      subfields CA1 and CA3. In the cerebellum, the neurochemical alterations were
      associated with Purkinje cell loss and increased GFAP immunoreactivity in the
      white matter. However, animals subjected to either stress or chemicals alone did
      not show any of these changes in comparison to vehicle-treated controls.
      Collectively, these results suggest that prolonged exposure to a combination of
      stress and the chemicals PB, DEET, and permethrin can produce significant damage
      to the cerebral cortex, hippocampus, and cerebellum, even in the absence of
      apparent BBB damage. As these areas of the brain are respectively important for
      the maintenance of motor and sensory functions, learning and memory, and gait and
      coordination of movements, such alterations could lead to many physiological,
      pharmacological, and behavioral abnormalities, particularly motor deficits and
      learning and memory dysfunction.

PMID- 14675907
TI  - Genetics, lifestyle and the roles of amyloid beta and oxidative stress in
      Alzheimer's disease.
AB  - This paper reviews a wide range of recent studies that have linked AD-associated
      biochemical and physiological changes with oxidative stress and damage. Some of
      these changes include disruptions in metal ion homeostasis, mitochondrial damage,
      reduced glucose metabolism, decreased intracellular pH and inflammation. Although
      the changes mentioned above are associated with oxidative stress, in most cases,
      a cause and effect relationship is not clearcut, as many changes are interlinked.
      Increases in the levels of Abeta peptides, the main protein components of the
      cerebral amyloid deposits of AD, have been demonstrated to occur in inherited
      early-onset forms of AD, and as a result of certain environmental and genetic
      risk factors. Abeta peptides have been shown to exhibit superoxide dismutase
      activity, producing hydrogen peroxide which may be responsible for the
      neurotoxicity exhibited by this peptide in vitro. This review also discusses the
      biochemical aspects of oxidative stress, antioxidant defence mechanisms, and
      possible antioxidant therapeutic measures which may be effective in counteracting
      increased levels of oxidative stress. In conclusion, this review provides support
      for the theory that damage caused by free radicals and oxidative stress is a
      primary cause of the neurodegeneration seen in AD with Abeta postulated as an
      initiator of this process.

PMID- 14675908
TI  - Relationships between visceral, trunk and whole-body adipose tissue weights by
      cadaver dissection.
AB  - BACKGROUND: Despite the important association of central adiposity and
      cardiovascular and other risk factors, there are only three reported values for
      directly weighed visceral adipose tissue (AT). All other reported values are
      based on medical imaging techniques. OBJECTIVE: The study aimed to investigate
      the relationships between visceral, trunk and total AT weights in older men and
      women. METHODS: Data was obtained from the combination of two studies involving
      the complete dissection of 15 male and 16 female cadavers (age range 55-94 years)
      and allowed for compartmentation into skin, AT, muscle, bone and a residual
      component, divided over six body segments: head, trunk, legs and arms. Visceral
      AT was separated from trunk subcutaneous AT. All tissues were weighed. RESULTS:
      Visceral AT weights ranged from 0.3 to 5.8 kg. Mean values were 3.00 +/- 1.52 kg
      (mean +/- SE) for the men and 3.24 +/- 1.67 kg for the women. These were not
      significantly different (p = 0.68), but visceral AT weight, expressed as a
      percentage of total body AT weight was significantly greater (p = 0.02) in the
      men (16.8 +/- 5.4%) than in the women (12.9 +/- 3.5%). Correlations between
      visceral AT weight and the weight of subcutaneous AT of the trunk were highly
      significant (men, r = 0.70, women, r = 0.81, p < 0.005), with similar slopes for
      the two sexes. The correlation coefficients of visceral with total body AT
      weights were even greater (men, r = 0.83 and women, r = 0.96, p < 0.0001).
      CONCLUSIONS: In this sample of older Belgians, visceral AT is strongly related to
      total body adiposity, corresponding to an increment of about 200 g of visceral AT
      for every kilogram of total AT in men and about 180 g in women. Because of this
      relationship, techniques such as skinfold calipers and ultrasound for assessing
      whole body fatness from measurement of only the subcutaneous layer are thus able
      to account for visceral adiposity.

PMID- 14675909
TI  - 'Thus the Colliers and their wives...': migration, mate choice and population
      structure of some County Durham parishes in the mid-19th century.
AB  - AIM: Historical accounts of the mining population in County Durham, UK, offer two
      persistent representations of demographic behaviour--substantial mobility and
      occupational endogamy--which would influence the distribution of genes in the
      population. The aim of this paper is to test these predictions against 19th
      century demographic data, comparing miners with other contemporary occupations.
      SUBJECTS AND METHODS: Four parishes in County Durham yielded data on 3653
      birthplace-residence distances, calculated from locations recorded in the 1851
      census enumerators' books, and on occupational endogamy and exogamy for 3784
      marriages recorded in the Anglican registers, 1834-76. Endogamy was analysed by
      log-linear models and odds ratios. RESULTS: Median migration distances were
      similar in the miners and other occupations, though the proportion of migrants
      among the miners (99.7%) was higher than agricultural (87.0%) and general
      labourers (91%). Endogamy in the miners (76%) was higher than in other
      populations (maximum 39%), but further analysis showed that the miners' tendency
      to marry women from the same occupational background was less than among
      agricultural labourers or professional men. CONCLUSION: Predictions of high
      migration rate and endogamy among the mining populations were upheld, but there
      was little evidence that the behaviour of the miners differed from other
      occupational groups.

PMID- 14675910
TI  - Urban-rural contrasts in the growth status of school children in Oaxaca, Mexico.
AB  - OBJECTIVES: The growth status of school children resident in an urban colonia and
      in a rural indigenous community in Oaxaca, southern Mexico, was considered in the
      context of two objectives, current status and the magnitude of urban-rural
      differences over a span of about 30 years. Both communities were initially
      surveyed in 1968 and 1972. MATERIALS AND METHODS: Height, body mass, segment
      lengths, skeletal breadths, limb circumferences, and subcutaneous fatness were
      taken on 361 rural (177 boys, 184 girls) and 339 urban (173 boys, 166 girls)
      school children, aged 6-13 years. Additional variables were derived. RESULTS:
      Height and body mass were significantly greater in urban compared with rural
      children. Sitting height, estimated leg length and skeletal breadths on the trunk
      were also larger in urban than in rural school children, but only the difference
      in skeletal breadths was significant after age and body size were statistically
      controlled. Urban and rural children did not consistently differ in skeletal
      breadths on the extremities and limb circumferences. Subcutaneous fatness was
      more variable. After controlling for age and body size, rural girls had thicker
      skinfolds. The magnitude of the urban-rural difference in boys in 2000 was
      greater for body mass, BMI and triceps skinfold, and reduced for height, sitting
      height, leg length, and arm and estimated arm muscle circumferences compared with
      1970. The magnitude of the urban-rural difference in girls was greater in 2000
      than 30 years earlier for body mass, height, sitting height, leg length and BMI.
      Urban-rural differences for arm and arm muscle circumferences and the triceps
      skinfold were slightly smaller over the interval. CONCLUSIONS: Children resident
      in an urban colonia were taller and heavier than children resident in a rural
      indigenous community. After controlling for age and body size, urban-rural
      differences in skeletal breadths and limb circumferences were reduced or
      eliminated, but skinfold thicknesses were greater in rural girls. The magnitude
      of urban-rural differences in body size has decreased over approximately 30 years
      in boys, but has increased in girls.

PMID- 14675911
TI  - Utility of different body composition indicators: demographic influences and
      associations with blood pressures and heart rates in adolescents (Heartfelt
      Study).
AB  - PRIMARY OBJECTIVE: To compare the utility of 10 commonly used body composition
      indicators (BCIs) in relation to demographic characteristics and cardiovascular
      risk factors. RESEARCH DESIGN: A cross-sectional, school sample was studied.
      SUBJECTS: Three hundred and eighty-four Black, White and Hispanic adolescents 11
      16 years of age from Houston, Texas, USA (Heartfelt Study) were studied. METHODS:
      BCIs include impedance and skinfold estimates of fat-free mass (FFM); fat mass
      (FM) and per cent body fat (PBF); resistance mass index (RMI); body mass index
      (BMI); and waist and abdomen circumferences. The cardiovascular risk factors
      (blood pressures/heart rates) are summarized by factor analysis. Sexual maturity
      was clinically assessed. RESULTS: Two distinct classes of BCIs emerged with
      respect to demographic influences: (1) RMI, impedance and skinfold estimators,
      for which sexual dimorphism is evident, and (2) BMI and circumferences, for which
      it is not. All BCIs were strongly related to general (systolic) blood pressure,
      but only body fat variables were related to heart rates. Skinfold-derived FM, PBF
      and mid-body circumferences were the variables most strongly related to
      cardiovascular risk factors. CONCLUSIONS: RMI, impedance or skinfold estimators
      are necessary for research requiring an accurate description of body composition
      changes during adolescence and for assessing the role of lean and fat tissue in
      disease aetiology. A 2-skinfold method is just as effective as the more
      complicated impedance. Mid-body circumferences are closely related to blood
      pressures and heart rates, suggesting their importance as indicators of abdominal
      fat in adolescents.

PMID- 14675912
TI  - Second to fourth digit ratio, body mass index, waist-to-hip ratio, and waist-to
      chest ratio: their relationships in heterosexual men and women.
AB  - BACKGROUND: Prenatal sex steroids have been broadly discussed in terms of their
      possible effect on brain differentiation, whereas pubertal/adult sex hormones are
      thought to be the main regulators of sexually dimorphic physical features in
      males and females. Assessing prenatal steroid exposure has previously been
      difficult but evidence now suggests that finger length ratio may provide a
      'window' into prenatal hormone exposure. The length of the second digit (the
      index finger) relative to the length of the fourth digit (the ring finger) is
      sexually dimorphic as males have a lower second to fourth digit ratio (2D:4D).
      The sexual dimorphism is determined as early as the 14th week of fetal life, and
      remains unchanged at puberty. There is evidence that sex differences in 2D:4D
      arise from in utero concentrations of sex steroids, with a low 2D:4D (male
      typical ratio) being positively related to prenatal testosterone, while a high
      2D:4D (female typical ratio) is positively associated with prenatal oestrogen.
      AIM: The studied aimed to determine whether, and to what extent, adult sexually
      dimorphic physical traits, which are largely determined at puberty, relate to
      traits that are largely determined in utero. This work examined the relationship
      between three sexually dimorphic traits--body mass index (BMI), waist-to-hip
      ratio (WHR) and waist-to-chest ratio (WCR)--and digit ratio. PARTICIPANTS AND
      METHODS: BMI, WHR and WCR were assessed in 30 heterosexual male and 50
      heterosexual female participants by recording their body height, weight, and
      measuring their waist, hip and chest circumference. Digit lengths of the second
      and fourth fingers were measured from photocopies of the ventral surface of the
      hand and by actual finger measurements. RESULTS: Digit ratio was found to be
      significantly lower in men than in women. Significant negative correlations were
      found between female's left and right hand 2D:4D, waist and hip circumference,
      and WCR. In males, BMI was found to be positively related to digit ratio but
      remained significant only for left hand 2D:4D. Generally, the relationships were
      stronger for females than for males. Although not all relationships were found to
      be significant, they were in accord with our predictions. CONCLUSION: In addition
      to an activational effect of sex hormones at puberty, the present data suggest an
      early organizational effect of sex hormones through the association between
      indices of female body shape, male BMI, and human finger length patterns.

PMID- 14675913
TI  - Relationship between arm span and stature in Malawian adults.
AB  - OBJECTIVE: The aim of this cross-sectional study was to assess the relationship
      between height and arm span in adult Malawians. SUBJECTS AND METHODS: 142 males
      and 128 females between the ages 20 and 76 years were recruited from among the
      patients attending various clinics at Queen Elizabeth Central Hospital, Blantyre,
      Malawi. All subjects were free from physical deformities. The anthropometric
      measurements included standing height and arm span. RESULTS: The arm span
      exceeded height in all age groups of males and females. The mean difference
      between the height and arm span values for females was 9.9 +/- 4.9 cm (t = 16.28,
      p<0.001) and for males was 11.6 +/- 4.4 cm (t = 14.74, p<0.001). The gender
      difference between height and arm span measurements was statistically significant
      (t = 9.58, p<0.001 and t = 10.24, p<0.001, respectively). Correlation of arm span
      and height for males was 0.871 and for females was 0.815. Prediction equations
      were derived from regression analysis. RSD values were 8.709 and 6.914 for
      equations for males and females, respectively. CONCLUSIONS: Stature of Malawian
      adults can be estimated from arm span measurements using regression equations.

PMID- 14675915
TI  - Enhanced post-ischaemic recovery in rabbit kidney after pretreatment with an
      indeno-indole compound and ascorbate monitored in vivo by 31P magnetic resonance
      spectroscopy.
AB  - OBJECTIVE: To investigate whether combined pretreatment with lipid- and water
      soluble antioxidants gave better restoration of energy phosphates after ischaemia
      reperfusion of rabbit kidneys than single pretreatment with a lipid-soluble
      antioxidant. MATERIAL AND METHODS: Thirteen New Zealand white rabbits were used
      for the study. Changes in energy phosphates were measured in vivo using volume
      selective 31P magnetic resonance spectroscopy. The indeno-indole compound H290/51
      was chosen as a lipid-soluble antioxidant and ascorbate as a water-soluble
      antioxidant. RESULTS: The combined pretreatment led to significantly better
      restoration of the beta-adenosine triphosphate:inorganic phosphate ratio after 60
      min of ischaemia and 120 min of reperfusion compared with the single
      pretreatment. Analyses of blood pressure and blood gas changes showed that the
      beneficial effect of combined pretreatment was not caused by a better general
      condition of the animals in that group but by a direct effect on the kidneys.
      CONCLUSIONS: Combined pretreatment with lipid- and water-soluble antioxidants
      leads to better restoration of energy phosphates in rabbit kidneys subjected to
      ischaemia-reperfusion compared with single pretreatment with a lipid-soluble
      antioxidant.

PMID- 14675916
TI  - Long-term protective effects of hypothermia on reperfusion injury post-testicular
      torsion.
AB  - OBJECTIVE: As many as two-thirds of salvaged testes post-torsion will atrophy
      within 2 years. Subsequent testicular damage is due at least in part to an
      ischaemia/reperfusion injury. Thus we analysed the long-term protective effects
      of subjecting the ischaemic testis to hypothermia in an attempt to prevent or
      attenuate subsequent testicular damage. MATERIAL AND METHODS: Forty male Sprague
      Dawley rats (mean age 97 days; mean weight 408 g) were randomized to one of two
      groups. The left testis was removed as a control and the right testis was
      subjected to torsion through 720 degrees in a clockwise direction and maintained
      in this position for 3 h. Half of the models were subjected to hypothermia by
      submerging the testis in a cooling bath, which was kept at a constant temperature
      of 2-4 degrees C for the final hour prior to detorsion. Testes were retrieved at
      1 and 12 weeks and examined by a single blinded pathologist using the following
      histological criteria: mean seminiferous tubular diameter, mean tubular wall
      thickness (MTWT) and Johnsen's score. RESULTS: Histological examination revealed
      significant injury after 1 week of reperfusion in both groups. However, after 12
      weeks of reperfusion there was a marked benefit seen in the testes subjected to
      hypothermia. MTWT (p=0.007) and Johnsen's score (p=0.05) were significantly
      better in the cooled testes after 12 weeks of reperfusion. CONCLUSION:
      Hypothermia reduces the degree of long-term testicular damage post-torsion and,
      if applied in clinical practice, may improve long-term salvage rates.

PMID- 14675917
TI  - Non-systematic screening for prostate cancer in Sweden--survey from the National
      Prostate Cancer Registry.
AB  - OBJECTIVE: The large increase in the incidence of prostate cancer is largely due
      to testing of serum levels of prostate-specific antigen (PSA). Little is known
      about how PSA testing is used in clinical practice outside of screening
      programmes. Essentially, PSA can be used in the health check-ups of men without
      symptoms as a form of non-systematic screening or in the work-up of symptomatic
      patients. The aim of this study was to investigate the cause of initiating a work
      up leading to a diagnosis of prostate cancer, with emphasis on T1c tumours.
      MATERIAL AND METHODS: Data on the cause of initiation of work-up leading to a
      diagnosis of prostate cancer were retrieved from the National Prostate Cancer
      Registry for 6361 incident cases in tumour category T1c and local stages T2, T3
      and T4 registered in Sweden in 2000. RESULTS: For 1496 cases in tumour category
      T1c (non-palpable tumours detected during work-up of elevated PSA), the cause of
      PSA testing was health check-ups in 32% of cases, work-up of symptoms suspected
      to emanate from the prostate in 51% and other causes/not reported in 17%. For all
      stages combined, the cause of initiation of the diagnostic work-up was health
      check-ups in 18% of cases, symptoms in 68% and other causes/not reported in 14%.
      CONCLUSION: Non-systematic screening using PSA testing has been introduced in
      Sweden. However, prostate cancer is still most commonly diagnosed during the work
      up of symptomatic patients.

PMID- 14675918
TI  - Free-to-total prostate-specific antigen ratio as a predictor of non-organ
      confined prostate cancer (stage pT3).
AB  - OBJECTIVE: To evaluate whether the free-to-total prostate-specific antigen (F/T
      PSA) ratio can be used to differentiate between stage pT2 and pT3 prostate
      cancer. MATERIAL AND METHODS: A total of 176 consecutive patients from the
      Goteborg Screening Study (median T-PSA 4.2 ng/ml) who underwent radical
      prostatectomy (without neoadjuvant hormonal therapy) were included in the study.
      The pT stage was correlated with classical risk factors such as T-PSA and Gleason
      sum and the impact of the F/T-PSA ratio was evaluated. RESULTS: A total of 42/176
      patients (23.9%) had stage pT3 prostate cancer. Patients with an F/T-PSA ratio in
      the lowest quartile (<10.7%) had extracapsular tumor growth in 46.5% of cases,
      compared to 16.7% for those with an F/T-PSA ratio >10.7% (p=0.0002). Patients
      with high-risk features (T-PSA >10 ng/ml or Gleason sum > or =7) had a high risk
      (54-60%) for stage pT3 prostate cancer. In low-risk patients, the subgroup with
      an F/T-PSA ratio <10.7% had a risk of 37.0%, compared to only 13.3% for those
      with a ratio of >10.7% (p=0.0092). CONCLUSIONS: In patients with low-risk early
      stage prostate cancer, the F/T-PSA ratio provides statistically significant,
      independent and clinically relevant preoperative information about the risk of
      extracapsular tumor growth.

PMID- 14675919
TI  - Hyperventilation response in the electroencephalogram and psychiatric problems in
      children with primary monosymptomatic nocturnal enuresis.
AB  - OBJECTIVES: The aim of this study was to determine the frequency of an increased
      hyperventilation (HV) response in the electroencephalogram and to compare the
      results of psychometric assessments and electroencephalography (EEG) patterns in
      children with and without primary monosymptomatic nocturnal enuresis and in dry
      siblings of enuretics. We also compared the results of psychometric assessments
      and EEG patterns between enuretic and non-enuretic children. MATERIAL AND
      METHODS: The study included 89 children divided into three groups: 41 with
      primary monosymptomatic nocturnal enuresis, their 29 dry siblings and 19 with no
      history of voiding dysfunction (controls). Resting EEG changes were evaluated in
      all children. In addition to a psychiatric evaluation, the Maudsley Obsessive
      Compulsive Questionnaire, the Beck Child Depression Inventory and the State and
      Trait Anxiety Inventory for Children were used to assess obsessive-compulsive
      disorder, depression and anxiety, respectively. RESULTS: The time at which real
      words were first spoken occurred significantly later in enuretic children
      (p<0.01). The frequency of EEG abnormalities was significantly higher in the
      enuresis group and in their dry siblings than in the control group (p<0.01).
      Additionally, as an indicator of cortical dysmaturity, an increased HV response
      was observed more often in enuretic children and their dry siblings than in the
      control group (p<0.001). Anxiety scores for the enuretic children were higher
      than those for the controls (p<0.01). There was no significant difference in
      psychiatric problems between the enuresis and control groups (p>0.05).
      CONCLUSIONS: The increased frequency of a high-level HV response in resting-state
      EEG recordings and the anxiety scores suggested that delayed cortical maturity
      and high anxiety may be important factors in the pathogenesis of primary
      monosymptomatic nocturnal enuresis. The HV responses in the dry siblings of the
      enuretic children may emphasize the relationship between insufficient cerebral
      maturation and the genetic origin of nocturnal enuresis.

PMID- 14675920
TI  - Percutaneous nephrolithotomy for pediatric stone disease--our experience with
      adult-sized equipment.
AB  - OBJECTIVE: We evaluated the outcomes and complications of percutaneous
      nephrolithotomy (PNL) operations performed in pediatric patients using adult
      sized surgical equipment at our center. MATERIAL AND METHODS: The medical and
      surgical records of 23 children who underwent a total of 25 PNL operations using
      24 or 26 F rigid nephroscopes were evaluated retrospectively. The following
      aspects were considered: stone burden; duration of surgery and complications;
      details concerning recovery, success, residual fragments and auxiliary
      procedures; and follow-up details. RESULTS: The success rate of a single PNL
      session was 70.8%; with the use of auxiliary procedures this was increased to
      91.6%. Perioperative and early postoperative complications were excessive
      bleeding and transfusion in two patients, hydro-pneumothorax in one, perforation
      of the collecting system in three and urinoma in one. Complications were more
      common in children aged <7 years or with staghorn stones. The mean time to
      catheter removal was 3.4 days and the mean hospitalization time was 4.8 days.
      Idiopathic hypercalciuria, hypocitraturia, cystinuria and hyperoxaluria were
      diagnosed in two, two, one and three patients, respectively. CONCLUSION:
      Performing PNL with adult-sized equipment is associated with significant
      complications in children aged <7 years or with staghorn stones. This treatment
      should not be considered in routine clinical practice. As all stone-removal
      methods are associated with complications, PNL should be used only if other
      methods fail or are unavailable.

PMID- 14675921
TI  - Recurrence of renal lithiasis.
AB  - OBJECTIVE: It is well known that all renal stones are associated with a high
      recurrence rate. The aim of this paper is to study the different types of renal
      calculi recurrence. MATERIAL AND METHODS: The study included 220 patients who had
      produced two or more renal calculi over a period of <5 years (total 634 calculi).
      The procedure used to study renal calculi involved appropriate combinations of
      stereoscopic microscopy with infrared spectrometry and scanning electron
      microscopy coupled with X-ray microanalysis. RESULTS AND CONCLUSION: Recurrent
      stone-formers can be classified into two large groups: those who always produce
      the same type of calculus (the most common type of recurrence was calcium oxalate
      dihydrate, followed by calcium oxalate monohydrate non-papillary and calcium
      oxalate monohydrate papillary calculi); and those who produce different types of
      renal calculi (the most frequent recurrences in this group were the changes
      calcium oxalate dihydrate-->calcium oxalate dihydrate/hydroxyapatite and calcium
      oxalate monohydrate-->calcium oxalate dihydrate).

PMID- 14675922
TI  - Long-term results of contact laser versus transurethral resection of the prostate
      in the treatment of benign prostatic hyperplasia with small or moderately
      enlarged prostates.
AB  - OBJECTIVE: To evaluate the long-term results of contact laser vaporization (CLV)
      of the prostate and transurethral resection of the prostate (TURP) in patients
      with symptomatic bladder outflow obstruction (BOO) caused by benign prostatic
      hyperplasia (BPH) with prostates smaller than 40 ml. MATERIAL AND METHODS: A
      total of 52 patients with lower urinary tract symptoms (LUTS) and urodynamically
      confirmed BOO caused by BPH with glands smaller than 40 ml were treated by means
      of CLV or TURP in a randomized trial. Changes in symptom score, urodynamics and
      prostate volume were evaluated during a 4-year follow-up period. RESULTS: A total
      of 42 (81%) of the patients were available for review at 4 years. The re
      operation rate was 1/26 for each treatment. A sustained improvement in median
      Danish Prostate Symptom Score was seen in the laser group from 18 (range 5-54) to
      5 (0-34) and in the TURP group from 18 (4-46) to 4 (0-18) (p<0.001 for both). A
      sustained improvement in maximum urinary flow rate was also seen in the laser
      group from 8.3 (4.8-19.6) ml/s to 14.3 (10.1-33.6) ml/s (p<0.001) and in the TURP
      group from 8.6 (5.0-15.9) ml/s to 16.1 (7.7-39.6) ml/s (p<0.01), without
      differences between the study groups. Median detrusor pressure at maximum urinary
      flow rate decreased significantly after both treatments, in the CLV group from 64
      (32-112) cmH2O to 38 (18-65) cmH2O and in the TURP group from 57 (40-137) cmH2O
      to 28 (9-44) cmH2O (p<0.001 for both), and at 48 months was significantly higher
      in the laser group (p<0.01). At 4 years, 7/22 (32%) of the laser patients and
      2/20 (10%) of the TURP patients were urodynamically obstructed. Post-void
      residual at 48 months was significantly lower in the TURP group than in the CLV
      group. Median prostate volume was smaller after TURP at 6 and 48 months (p<0.05).
      CONCLUSIONS: Long-term data of CLV and TURP treatments for BPH with small or
      moderately enlarged prostates indicate no significant difference in the relief of
      symptoms or in the rate of re-operations. However, the number of patients in this
      study was small and consequently the power to detect differences between the
      study groups was low. Regarding most objective outcome parameters, long-term
      follow-up revealed a slight advantage of TURP over CLV.

PMID- 14675923
TI  - Interstitial laser coagulation versus transurethral resection of the prostate for
      benign prostatic enlargement--a prospective randomized study.
AB  - OBJECTIVE: Interstitial laser coagulation (ILC) of the prostate is a minimally
      invasive method for treating symptomatic benign prostatic enlargement (BPE). We
      performed a prospective randomized study to compare the clinical outcomes of ILC
      and transurethral resection of the prostate (TURP). MATERIAL AND METHODS: Between
      December 1997 and February 2000, 38 patients with moderate-to-severe symptomatic
      BPE were included in the study. Seven were subsequently excluded due to
      intercurrent disease or protocol violation and the remaining 31 were randomized
      to either TURP (n=11) or ILC (n=20). A suprapubic tube was inserted in all ILC
      treated patients, and ILC was performed as an outpatient procedure when feasible.
      Data were recorded preoperatively and at 3-month and 1-year follow-up. The
      assessment parameters were International Prostate Symptom Score (IPSS), uroflow,
      prostate volume determined by means of transrectal ultrasound and postvoid
      residue. RESULTS: At 1-year follow-up, uroflowmetry indicated a more pronounced
      increase in peak urinary flow rate (Qmax) in the TURP patients than in the ILC
      subjects (p<0.02). Differences in postvoid residue, IPSS and prostate volume
      between the two treatments could not be evaluated due to the small number of
      patients in each group. Postoperative urinary tract infections occurred in 13 ILC
      patients but in only one TURP subject, and catheterization was done for 24 days
      after ILC and for 2 days after TURP. The study was ended prematurely due to the
      prolonged postoperative catheterization and the high rate of urinary tract
      infections in the ILC patients. CONCLUSIONS: At 1-year follow-up, the increase in
      Qmax was smaller in the ILC subjects than in the TURP patients. The ILC subjects
      had comparatively more postoperative urinary tract infections and more prolonged
      postoperative catheterization than the TURP patients.

PMID- 14675924
TI  - Exclusion of WTAP and HOXA13 as candidate genes for isolated hypospadias.
AB  - OBJECTIVE: Different molecular factors have been identified as being associated
      with isolated or syndrome-associated forms of hypospadias. Nevertheless, the
      etiology of hypospadias is unknown in 70% of cases. As mutations in the homeobox
      gene A13 (HOXA13) were all found to be associated with hypospadias in affected
      males, some types of mutation may solely lead to the isolated form. Moreover,
      mutations in the Wilms' tumor suppressor gene WT1 have been found in patients
      with hypospadias without evidence of a Wilms' tumor and, therefore, its recently
      identified associated protein (WTAP) may be a further candidate gene for the
      genesis of hypospadias. MATERIAL AND METHODS: A total of 37 patients affected
      with different forms of isolated hypospadias were analyzed for mutations in their
      HOXA13 and WTAP genes. RESULTS: With the exception of two novel WTAP
      polymorphisms, no mutations could be observed. CONCLUSIONS: There seems to be no
      evidence that isolated hypospadias is commonly caused by mutations in HOXA13 or
      WTAP genes.

PMID- 14675925
TI  - A classification based on peak systolic velocity and end diastolic velocity
      predicts sildenafil citrate success.
AB  - OBJECTIVE: To attempt to predict the success rate of sildenafil citrate in
      erectile dysfunction patients using penile Doppler ultrasonography (PDU)
      measurements of peak arterial velocity and end diastolic velocity. MATERIAL AND
      METHODS: A total of 212 patients (age range 27-76 years) with vascular
      pathologies were included in the study. Following a PDU test, the patients were
      divided into arterial insufficiency, veno-occlusive dysfunction and mixed
      vascular pathology groups. Subsequently, patients were given sildenafil citrate
      50 mg and re-evaluated 1 month later to determine its efficacy. If it was
      ineffective, the dose was increased to 100 mg and patients were reassessed.
      Arterial insufficiency and veno-occlusive dysfunction patients were classified
      into mild, moderate and severe groups depending on peak systolic and end
      diastolic velocities. RESULTS: The overall response rate in patients with
      arterial insufficiency was 74.5%, regardless of the degree of arterial
      insufficiency or the dose of sildenafil. The severe arterial insufficiency group
      had a much better response to 100 mg compared to 50 mg doses of sildenafil.
      Although the 50 mg sildenafil dose was effective in patients with minimal veno
      occlusive dysfunction, 100 mg was better than 50 mg to achieve adequate erection
      in the mild and severe veno-occlusive dysfunction groups. CONCLUSIONS: Sildenafil
      was ineffective in patients with severe arterial and venous insufficiency. PDU
      and a simple classification of PDU velocity measurements can provide some
      important clues to the prognosis of treatment and avoid overtreatment and
      unnecessary office visits.

PMID- 14675926
TI  - Operative mortality after nephrectomy for renal cell carcinoma.
AB  - OBJECTIVE: To study the rate and causes of operative and treatment-related
      mortality after nephrectomy for renal cell carcinoma (RCC) in Iceland. MATERIAL
      AND METHODS: This retrospective population-based study included all patients who
      underwent nephrectomy for RCC in Iceland between 1971 and 2000. Patients who died
      <30 days after the operation were analyzed and compared to those who survived
      surgery. Disease stage, tumor size, patient age and preoperative American Society
      of Anesthesiologists classification were compared between the two groups. Autopsy
      records were examined to determine the causes of death. RESULTS: During the study
      period 880 patients were diagnosed with RCC and 575 (65%) of them underwent a
      nephrectomy, 116 (20%) with palliative intent. Operative mortality (OM) was 2.8%
      and did not change during the 30-year period. Patients with OM were significantly
      older than those without (73 vs 64 years, respectively) but disease stage, tumor
      size, ASA classification and gender were comparable between the groups. OM was
      comparable for patients operated on with palliative (3.4%) vs. curative (2.6%)
      intent (ns). Median time of death was 10 days postoperatively but no patient died
      intraoperatively. Causes of death were peri- and postoperative bleeding in five
      patients, infection/sepsis in four, arrhythmia in three, acute renal failure in
      two, pulmonary embolism in one and multiorgan failure in one. CONCLUSIONS: OM
      after nephrectomy for RCC has remained low during the past three decades in
      Iceland. It is most often caused by perioperative bleeding and infections. We
      find that the low OM in patients with metastases gives support to the use of
      palliative nephrectomy as a treatment option when other forms of treatment have
      failed.

PMID- 14675927
TI  - Condyloma acuminatum-like lesion of the urinary bladder progressing to invasive
      spindle cell carcinoma.
AB  - Condyloma acuminata of the urinary bladder is a rare finding, particularly in the
      absence of similar lesions of the external genitalia. We present a case in which
      an isolated condyloma acuminatum-like lesion rapidly progressed to a poorly
      differentiated spindle cell carcinoma, underlying the need for careful endoscopic
      follow-up of patients with such lesions.

PMID- 14675928
TI  - Testicular microlithiasis--one case and four points to note.
AB  - A 38-year-old man with non-specific scrotal complaints was found to have
      bilateral testicular microlithiasis (TM) sonographically. MRI of the testes
      failed to depict microlithiasis. Bilateral double biopsies of the testes revealed
      testicular intraepithelial neoplasia (TIN; carcinoma in situ of the testis) in
      only one of the two biopsies from the right testis. At the request of the patient
      the biopsies were repeated, with the same histological result. A right-sided
      orchiectomy was performed. Histology disclosed TIN in only some tubules of the
      lower pole of the testis. This case highlights four interesting points: (i) TM
      may be associated with testicular malignancy; (ii) MRI does not depict TM; (iii)
      TIN is arranged focally within the testis; and (iv) a two-site biopsy may
      increase the sensitivity of the diagnosis of TIN.

PMID- 14675930
TI  - Welfare trends of the 1990s in Iceland.

PMID- 14675929
TI  - Amyloidosis of the seminal vesicle--a case report and review of the literature.
AB  - The finding of amyloid deposits in the seminal vesicles has been known for many
      years. The deposits are usually localized and asymptomatic. In recent years
      seminal vesicle amyloidosis has been reported to simulate prostate and bladder
      cancer invasion on MRI. We therefore feel that knowledge of the entity is
      important and present herein a typical case confirming the previous findings that
      amyloidosis of the seminal vesicles is a unique form of amyloidosis, a relatively
      common incidental finding and one that may be related to prostate cancer.

PMID- 14675931
TI  - Abortion rate and contraceptive practices in immigrant and native women in
      Sweden.
AB  - AIM: The aim of this study was to analyse whether immigrant women request induced
      abortion more frequently than Swedish-born women and, if so, to study possible
      explanations, including contraceptive practices and attitudes. METHODS: All women
      who requested induced abortion during a period of one year were included in the
      study. The 1289 women, of whom 36% were born outside Sweden, were interviewed by
      a nurse-midwife who, using a structured protocol, gathered information on
      socioeconomic factors, reasons for abortion, experience of contraceptive methods,
      and family planning counselling. The proportion of women with non-Swedish origin
      in the study population was compared with the official demographic statistics of
      the corresponding area. RESULTS: The number of women born outside Sweden who
      requested induced abortion was larger than expected from their proportion in the
      population. The immigrant women originated from 77 countries and four continents,
      the largest subgroup, 11%, coming from Iran. Immigrant women had less experience
      of contraceptive use, more previous pregnancies and more induced abortions than
      women born in Sweden. In a multivariate analysis, immigrant status and
      educational level were found to be independent risk factors for repeat abortion.
      CONCLUSION: Immigrant status seems to be an independent risk factor for induced
      abortion. The immigrant women originated from a wide range of cultures. There is
      no reason to believe that the women in this heterogeneous group should have any
      cultural factor in common that could explain their higher proneness to seek
      induced abortion. The most probable cause is that immigrant status is associated
      more often with low education, weak social network, poverty, unemployment, and
      being outside common pathways to healthcare.

PMID- 14675932
TI  - Non-response bias in a postal questionnaire survey on respiratory health in the
      old and very old.
AB  - AIMS: The authors wished to describe non-responders and reasons for non-response
      and determine the magnitude and direction of non-response bias in connection with
      a postal questionnaire study of respiratory symptoms and disease among the
      elderly. METHODS: An eight-page respiratory health questionnaire was mailed to
      subjects in a sex-age stratified random sample of the general population of
      Bergen, Norway, 70 years or older (n=2871). A reminder with repeat questionnaire
      was sent out to initial non-responders after three weeks. A random sample of non
      responders was interviewed by telephone. RESULTS: There were a total of 1649
      respondents (57.4%); 1356 to the initial mailing and 293 to the reminder mailing.
      The response rates were highest for the age group 70-74 years (76.6%) and fell
      dramatically with age (27.1% in age group 95+years). Men responded (63.7%) better
      than women (52.0%) and this was consistent at every age level. Late and non
      responders had slightly lower frequencies of respiratory symptoms but higher
      frequencies of current-smoker status. CONCLUSIONS: All found, differences between
      responders and non-responders were small and would have only minimal effects on
      the final prevalence estimates for respiratory symptoms and disease. In comparing
      the results based on initial responders to results based on all responders,
      associations between predictor variables and outcome variables were essentially
      the same, showing that a reminder had little effect on the results of the study.

PMID- 14675933
TI  - Causes of death between 1911-1950 in a Swedish province with a population
      characterized by longevity.
AB  - AIMS: Life expectancy in Sweden is among the highest in the world, and the
      province of Halland has the highest life expectancy in Sweden today. In an
      earlier paper the authors reported that life expectancy in the province of
      Halland in the south-west of the country was approx. 3.5 years above the national
      average between 1911 and 1950. The aim of this study was to explore the influence
      of different causes of death on life expectancy in Sweden and the distribution of
      these causes of death in Halland compared with Sweden as a whole during the same
      period of time. METHOD: Causes of death between 1911 and 1950 in the whole of
      Sweden and in Halland were obtained from the archives of Statistics Sweden. A
      trend analysis was performed on the impact of the various causes of death on life
      expectancy in Sweden. Calendar year, age, and sex were controlled for in a
      Poisson model. The distribution and incidence of the most frequent causes of
      death were compared between Halland and Sweden as a whole. RESULTS: The
      decreasing mortality risk due to infectious diseases and the simultaneous
      increase in the risk of mortality from tumours and circulatory diseases
      contributed most to the change in life expectancy in Sweden. In Halland there was
      a lower mortality risk in the seven most important causes of death, which
      accounted for approx 80% of all deaths during the study period. CONCLUSIONS: The
      lower mortality risk from infectious diseases mostly favoured the improvement in
      life expectancy in Halland up to the mid-1930s. Thereafter, a low mortality risk
      from tumours and particularly circulatory diseases gained increasing importance
      although there was always a difference in favour of Halland from the beginning of
      the study period. Thus, the positive trend in life expectancy that favours
      Halland today seems to have existed for a long period of time.

PMID- 14675934
TI  - Effect of living conditions in the parental home and youth paths on the social
      class differences in mortality among women.
AB  - AIMS: A longitudinal study was undertaken to assess the effects of parental home
      and youth paths on the adult social class differences in mortality among women.
      METHODS: The study used population registration data on all Finnish women aged 30
      34 in 1990 for whom information on their childhood characteristics and youth
      paths were available from the 1970, 1975, 1980, 1985, and 1990 censuses. Cause of
      death follow-up was for the period 1991-98 (1185 deaths). RESULTS: Adjusting for
      parental social class, family type, and number of siblings attenuated the effects
      of adult social class on cardiovascular disease mortality by 27%; for all
      external causes this attenuation was negligible. Educational, marital, and
      employment paths accounted for a substantial part (30-85%) of the social class
      differences in mortality for all specific causes of death. CONCLUSIONS: Although
      living conditions in the parental home were associated with mediating life
      trajectories in youth their effect on adult social class differences in mortality
      was moderate. Youth paths have a pervasive influence on mortality risks and
      social class differences in mortality in middle adulthood.

PMID- 14675935
TI  - Comparative intervention study among Danish daycare children: the effect on
      illness of time spent outdoors.
AB  - AIMS: The purpose of the study was to examine the correlation between illnesses,
      and in particular contagious illnesses, among daycare children and the amount of
      time spent outdoors, and whether through the intervention of increasing the
      amount of time spent outdoors it is possible to lower the incidence of illness.
      METHODS: The study was conducted among eight daycare centres within the same
      county. A total of 326 children, 17 homeroom groups, were divided into two study
      groups. Each of the two study groups had a two-month period in which the
      percentage of time spent outdoors per day was almost double that of the other
      study group. RESULTS: The overall frequency of sick days was 4%. There was no
      significant effect of spending more time outdoors on the number of illness
      episodes, length of the episode, or cause of illness. CONCLUSION: Our negative
      findings are in accordance with the theory that illness among daycare children is
      largely a result of contact among children and the hygiene standards of the
      institution, and thus these are the factors that may need to be addressed to
      reduce the level of illness among daycare children.

PMID- 14675936
TI  - Social participation, social capital and daily tobacco smoking: a population
      based multilevel analysis in Malmo, Sweden.
AB  - AIMS: The aim of this study was to investigate the influence of contextual and
      individual factors on daily tobacco smoking. METHODS: The public-health survey in
      Malmo 1994 is a cross-sectional study. A total of 5600 individuals aged 20-80
      years were invited to answer a postal questionnaire. The participation rate was
      71%. A multilevel logistic regression model, with individuals at the first level
      and neighbourhoods at the second, was performed. We analysed the effect (intra
      area correlation, cross-level modification and odds ratios) of individual and
      neighbourhood factors on smoking after adjustment for individual factors.
      RESULTS: Neighbourhood factors accounted for 2.5% of the crude total variance in
      daily tobacco smoking. This effect was significantly reduced when the individual
      factors such as education were included in the model. However, individual social
      capital, measured by social participation, only marginally affected the total
      neighbourhood variance in daily tobacco smoking. In fact, no significant variance
      in daily tobacco smoking remained after the introduction of the individual
      factors other than individual social capital in the model. CONCLUSION: In Malmo,
      the neighbourhood variance in daily tobacco smoking is mainly affected by
      individual factors other than individual social capital, especially socioeconomic
      status measured as level of education.

PMID- 14675937
TI  - Establishing a set of mental health indicators for Europe.
AB  - AIMS: This review presents the background work for developing a set of mental
      health indicators as part of a comprehensive health monitoring system in the
      European Union. The review focuses on the appraisal of mental health at
      population level with special emphasis on assessments that could be useful for
      mental health promotion. METHODS: A functional model of mental health is used to
      delineate variables important for a set of mental health indicators. Variables
      that are not possible to monitor at population level are not discussed here.
      Literature searches were conducted through the MEDLINE, PSYCHLIT, and
      SOCIOLOGICAL ABSTRACTS databases and available textbooks. RESULTS: The review
      presents findings from research seeking associations between mental health and
      ill health and different individual, social, economic, ecological, and service
      related characteristics. Specific domains as key starting points in establishing
      a set of mental health indicators are outlined according to the research
      findings. CONCLUSION: A set of mental health indicators can enhance the
      visibility of mental health issues in the European context. Ultimately the
      indicators could be used in estimating how the targets set for health policies
      are met, and whether there has been a measurable decrease in disability,
      suffering, and disease.

PMID- 14675938
TI  - Sickness certification practices of physicians: a review of the literature.
AB  - BACKGROUND: In most Western countries the responsibilities of physicians include
      assessing work ability and issuing certificates for sickness absence and
      disability pension. These tasks often have a substantial impact on the lives of
      patients and constitute a financial burden on employers, insurance companies, and
      communities. AIM: The aim was to review scientific studies on sickness
      certification practices of physicians published in English, Danish, Norwegian, or
      Swedish. METHOD: Analyses were carried out of studies searched for through
      literature databases, reference lists, and personal contacts. RESULTS: Twenty-six
      publications fulfilled the inclusion criteria. Most of these were published in
      the last decade. The studies focused on physicians, and occasionally on
      physicians and patients, but never on interaction between them. Data had
      generally been collected using questionnaires, some including case vignettes.
      There was a large variation in how long different physicians sickness-certified
      similar patients. Three comprehensive categories of studies were identified
      dealing with the following: (1). how physicians certify sickness; (2). factors
      that might affect the certification process; (i.e. elements related to the
      patient, to the physician, or to restrictions in insurance legislation); and (3).
      studies concerning attitudes. No studies were found that took into account the
      work conditions of the hospital or health-care organization in which the
      physician works. CONCLUSIONS: The research problems were seldom medical in nature
      but were instead carried out within the realm of behavioural science and should
      preferably be conducted using theories from behavioural, social, and public
      health scientific theories. Furthermore, factors such as gender, ethnicity, and
      power should be taken into consideration in studies on this complex phenomenon.

PMID- 14675939
TI  - Health for all: an alternative strategy.

PMID- 14675942
TI  - 3D-QSAR studies of some [[1-aryl(or benzyl)-1-(benzenesulphonamido)methyl]
      phenyl] alkanoic acid derivatives as thromboxane A2 receptor antagonists.
AB  - Thromboxane A(2) receptor antagonists have attracted much attention in recent
      times in the design of new agents that could be active against diseases such as
      thrombosis, asthma and myocardial ischemia. 3D-QSAR studies have been performed
      on a series of [[1-aryl(or benzyl)-1-(benzenesulphonamido)methyl] phenyl]
      alkanoic acid derivatives by using the receptor surface analysis (RSA) method.
      The RSA analysis was carried out on 31 analogues of which 25 were used in the
      training set and the rest considered for the test set. This study produced
      reasonably good predictive models with good cross-validated and conventional r(2)
      values in both the models.

PMID- 14675943
TI  - Interactions of the dimeric triad of HIV-1 aspartyl protease with inhibitors.
AB  - Strong hydrogen-bonding forces between the Thr26 and Thr26' of the protease
      stabilize the internal cage of the dimeric triad of the aspartyl HIV-1 protease
      (Asp25Thr26Gly27 and Asp25' Thr26'Gly27', respectively). The interaction of
      reversible inhibitors of HIV-1 protease is based on (i) strong hydrogen-bonding
      forces between the main chain (--CONH--) oxygen atoms of Gly27 and/or Gly27' and
      hydrogen-bond donating moieties of a drug, and (ii) hydrogen bonds between the
      oxygen of the catalytic Asp25 and/or Asp25' carboxylates and aliphatic hydroxyl
      groups of a drug. The free entry of natural substrates into the active-site
      cavity is sterically hindered by inhibitors, so that the catalytic Asp
      carboxylates cannot interact with natural substrates. Irreversible inhibitors
      interact with the nucleophilic carboxylate moiety of Asp25 of HIV-1 protease by
      covalent bonding.

PMID- 14675944
TI  - Synthesis and three-dimensional quantitative structure-activity relationship
      analysis of H3 receptor antagonists containing a neutral heterocyclic polar
      group.
AB  - Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis
      was applied to a series of H(3) receptor antagonists characterized by an
      imidazole ring, an alkyl spacer, and a heterocyclic polar moiety containing an
      imidazole or a thiazole ring, with a view to investigate the requirements for
      H(3) receptor affinity on rat cortex membranes. The compounds were aligned based
      on the hypothesis that the presence of a H-bond donor group in the polar portion
      of the molecule can increase H(3) receptor affinity. The 3D-QSAR analysis, which
      was performed using both the CoMFA and CoMSIA protocols, revealed that the
      presence of a H-bond donor group is not statistically relevant for H(3) receptor
      affinity. Based on this result, another alignment was adopted that took into
      consideration the structural features common to all compounds, namely the
      imidazole ring and the N atom with a free lone pair in the polar portion. The 3D
      QSAR models thus obtained showed that H(3) receptor affinity is modulated by the
      position and direction of the intermolecular interaction elicited by the polar
      group in the ligands.

PMID- 14675945
TI  - Quantitative structure-activity relationship study on some azidopyridinyl
      neonicotinoid insecticides for their selective affinity towards the drosophila
      nicotinic receptor over mammalian alpha4beta2 receptor using electrotopological
      state atom index.
AB  - Neonicotinoids are the most important class of synthetic insecticides
      increasingly used in agriculture and veterinary medicine. Fundamental differences
      between the nicotinic acetylcholine receptors (nAChRs) of insects and mammals
      confer remarkable selectivity of the neonicotinoids at insect nAChR over
      mammalian nAChR. To identify pharmacophoric requirements of azidopyridinyl
      neonicotinoids for their efficacy and selectivity towards the insect nAChR over
      the mammalian one, quantitative structure-activity relationship (QSAR) study was
      performed using electrotopological state atom (ETSA) indices. This study clearly
      showed that nitroimines, nitromethylenes, and cyanoimines are more selective to
      Drosophila nAChR and safe for human being, whereas N-substituted imines have
      affinity to mammalian receptor. Pharmacophore mapping for both the activities was
      done.

PMID- 14675946
TI  - Structure-based design of novel inhibitors of 3-deoxy-D-manno-octulosonate 8
      phosphate synthase.
AB  - 3-Deoxy-D-manno-octulosonate 8-phosphate (KDO8P) is the phosphorylated precursor
      of KDO, an essential sugar of the lipopolysaccharide of Gram negative bacteria.
      KDO8P is produced by a specific synthase (KDO8PS) by condensing arabinose 5
      phosphate (A5P) and phosphoenolpyruvate (PEP), with release of inorganic
      phosphate. As KDO8PS is present in bacteria and plants, but not in mammalian
      cells, and mutations that inactivate KDO8PS also block cell replication, KDO8PS
      is a promising target for the design of new antimicrobials that act by blocking
      lipopolysaccharide biosynthesis. Previous studies have shown that a compound
      mimicking an intermediate of the condensation reaction is a good ligand and a
      powerful inhibitor. Here we report on the crystallographic investigation of the
      binding to KDO8PS of new derivatives of this original inhibitor. The structures
      of the enzyme in complex with these compounds, and also with the PEP analogs, 2
      phosphoglyceric acid (2-PGA) and Z-methyl-PEP, point to future strategies for the
      design of novel inhibitors of KDO8PS.

PMID- 14675948
TI  - Assessment of mechanobiological models for the numerical simulation of tissue
      differentiation around immediately loaded implants.
AB  - Nowadays, there is a growing consensus on the impact of mechanical loading on
      bone biology. A bone chamber provides a mechanically isolated in vivo environment
      in which the influence of different parameters on the tissue response around
      loaded implants can be investigated. This also provides data to assess the
      feasibility of different mechanobiological models that mathematically describe
      the mechanoregulation of tissue differentiation. Before comparing numerical
      results to animal experimental results, it is necessary to investigate the
      influence of the different model parameters on the outcome of the simulations. A
      2D finite element model of the tissue inside the bone chamber was created. The
      differentiation models developed by Prendergast, et al. ["Biophysical stimuli on
      cells during tissue differentiation at implant interfaces", Journal of
      Biomechanics, 30(6), (1997), 539-548], Huiskes et al. ["A biomechanical
      regulatory model for periprosthetic fibrous-tissue differentiation", Journal of
      Material Science: Materials in Medicine, 8 (1997) 785-788] and by Claes and
      Heigele ["Magnitudes of local stress and strain along bony surfaces predict the
      course and type of fracture healing", Journal of Biomechanics, 32(3), (1999) 255
      266] were implemented and integrated in the finite element code. The fluid
      component in the first model has an important effect on the predicted
      differentiation patterns. It has a direct effect on the predicted degree of
      maturation of bone and a substantial indirect effect on the simulated
      deformations and hence the predicted phenotypes of the tissue in the chamber.
      Finally, the presence of fluid also causes time-dependent behavior. Both models
      lead to qualitative and quantitative differences in predicted differentiation
      patterns. Because of the different nature of the tissue phenotypes used to
      describe the differentiation processes, it is however hard to compare both models
      in terms of their validity.

PMID- 14675949
TI  - The effect of fixture neck design in a realistic model of dental implant: a
      finite element approach.
AB  - The aim of this work is to develop an accurate finite element model able to
      reproduce a standard experimental set-up for the evaluation of mechanical failure
      of a dental implant system. The considered system is composed of a fixture, an
      abutment and a connecting screw. We analysed the behaviour of the implant system
      considering three different designs of the fixture, in order to establish which
      one provides the better mechanical behaviour. After the definition of the
      numerical models, loading conditions were selected in order to reproduce the same
      stress state found in previous mechanical failure tests. Preloading and
      functional loading conditions were simulated. The analysis of the numerical
      results shows that the structure yielding is due to the fixture neck plastic
      deformation, that increases the load eccentricity and then the bending stress on
      the connecting screw. Only slight differences were found between the three
      implant systems in the amount and distribution of stress. The model reproduces
      properly the implant systems and the experimental set-up. The goodness of the
      model can be summarised as: realistic geometrical structure, elastoplastic model
      for the material description, correct definition of the contacts and the existing
      tolerance among the different system components, reproduction of the preloading
      stress condition. The present study permitted to define a valid procedure for the
      realization of numerical models of implant systems.

PMID- 14675950
TI  - Flexural and creep properties of human jaw compact bone for FEA studies.
AB  - The aim of this work was to improve the constitutive model of the human mandible
      and dentition system by taking into account the non-linear material properties of
      the structural boney matrix that forms the human jaw bone or mandible. Due to the
      specific structure of the jaw bone the time dependence of the mechanical
      properties also forms an important stage of the quantification process. The lack
      of specific experimental data of this type of material prevents the
      implementation of these properties into finite element simulations which results
      in poor quality modelling. Here an attempt was made to determine elastic and
      viscoelastic mechanical characteristics of the compact bone tissue forming the
      mandible. The elastic properties of compact bone were determined experimentally
      from 3 point bending tests and the viscoelastic properties were evaluated from
      creep tests in compression. A particular human jaw from this complex study was
      used to reconstruct a geometric model for further numerical experiments.

PMID- 14675951
TI  - Mechanical response of bone under short-term loading of a dental implant with an
      internal layer simulating the nonlinear behaviour of the periodontal ligament.
AB  - We consider a non-standard design for a fixed dental implant, incorporating a
      soft layer which simulates the presence of the periodontal ligament (PDL).
      Instead of being aimed at causing an a priori defined stress/strain field within
      the surrounding bone, upon loading, such a design simply tries to better
      reproduce the natural tooth-PDL configuration. To do this, the mechanical
      properties of the internal layer match those of the PDL, determined
      experimentally to be strongly nonlinear. Three-dimensional finite element
      analyses show that the presence of such a layer produces (i) a prosthesis
      mobility very similar to that of a healthy tooth, for several loading conditions,
      and (ii) a stress/strain distribution substantially different from that arising,
      upon loading, around a conventional implant. The lack of knowledge of the real
      mechanical fields existing, under loading, in the bone around a healthy tooth
      makes it very difficult to state that the stress distribution produced by the
      modified implant is "better" than that produced by the standard one.
      Nevertheless, the comparison of the results obtained here, with those of previous
      refined analyses of the tooth-PDL-bone system, indicates that the modified
      implant tends to produce a stress distribution in the bone, upon loading, closer
      to "natural" than that given by the standard one, within the limits imposed by
      the presence of threads coupling the implant with the bone.

PMID- 14675952
TI  - Detection and prediction of tooth mobility during the periodontitis healing
      process.
AB  - The focus of the article is on a generic approach to prediction of a healing
      process based on automatic measurement and modelling of mechanical disease
      indicators. As a specific example the healing process after treatment of advanced
      periodontitis is characterised and predicted based on measurement of tooth
      mobility (TM). For the measurement a new mechatronic instrument was developed
      that includes a pneumatically driven probe with incorporated sensors of tooth
      displacement and loading force. TM is measured by a computer controlled data
      acquisition system and predicted by a non-parametric regression. Similarly as in
      the characterisation of technical processes, a measured sample is described by TM
      time series detected on a particular patient, while the regression is determined
      by a set of samples obtained from a group of patients following periodontal
      therapy. The influence of surgical access therapy and systemic administration of
      metronidazole as an adjunct to the mechanical treatment is demonstrated. For this
      purpose the average changes of tooth mobility are determined on variously treated
      subgroups. A new method of healing process prediction is demonstrated and its
      performance is described by a prediction quality.

PMID- 14675953
TI  - A transversally isotropic elasto-damage constitutive model for the periodontal
      ligament.
AB  - A numerical formulation of an elasto-damage constitutive model was developed and
      implemented in a finite element software to investigate the biomechanical
      response of the periodontal ligament (PDL). The mathematical framework accounts
      for the description of large strains, anisotropy and inelastic phenomena. The
      anisotropic mechanical response is caused by the spatial orientation of the sub
      structures of the tissue, such as collagen fibres. Inelastic behaviour, induced
      by high level strains, is modelled by means of damage models. In vitro
      experimental testing on PDL samples from pigs was performed to obtain tensile
      stress-strain curves. A finite element analysis is presented in order to define a
      general numerical approach. A comparison of numerical and experimental data is
      provided in order to show the reliability and effectiveness of the formulation
      assumed.

PMID- 14675954
TI  - A transversely isotropic hyperelastic constitutive model of the PDL. Analytical
      and computational aspects.
AB  - This study describes the development of a constitutive law for the modelling of
      the periodontal ligament (PDL) and its practical implementation into a commercial
      finite element code. The constitutive equations encompass the essential
      mechanical features of this biological soft tissue: non-linear behaviour, large
      deformations, anisotropy, distinct behaviour in tension and compression and the
      fibrous characteristics. The approach is based on the theory of continuum fibre
      reinforced composites at finite strain where a compressible transversely
      isotropic hyperelastic strain energy function is defined. This strain energy
      density function is further split into volumetric and deviatoric contributions
      separating the bulk and shear responses of the material. Explicit expressions of
      the stress tensors in the material and spatial configurations are first
      established followed by original expressions of the elasticity tensors in the
      material and spatial configurations. As a simple application of the constitutive
      model, two finite element analyses simulating the mechanical behaviour of the PDL
      are performed. The results highlight the significance of integrating the fibrous
      architecture of the PDL as this feature is shown to be responsible for the
      complex strain distribution observed.

PMID- 14675955
TI  - A bone-remodelling scheme based on principal strains applied to a tooth during
      translation.
AB  - This paper investigates the role of principal strains within the periodontal
      ligament (PDL) during bone remodelling in orthodontics and particularly in the
      case of bodily motion (pure translation). Using analytical formulas of stress and
      strains within the PDL for the particular case of a paraboloidal central incisor
      during translation, the strains are directly related to the motion of the
      interface between the alveolar bone and the PDL, called bone surface. It is shown
      that both normal and shear strains within the PDL are of the same importance for
      bone surface motion. Moreover, both "mean average" and "geometrical average" of
      principal strains within the PDL play a significant role in the bone remodelling
      process, as they contribute with the same proportionality. In summary, the
      proposed formulas differ than previous ones that had been successfully applied to
      describe remodelling within long bones. The proposed theory is also sustained by
      a linear finite element analysis.

PMID- 14675956
TI  - Applications of surface-surface matching algorithms for determination of
      orthodontic tooth movements.
AB  - Orthodontic tooth movements are described as the differences between initial and
      final tooth positions. A computer based method for determination of tooth
      movements for different treatment methods was developed. A total of 20 casts of
      the upper jaw of patients treated with tooth positioners or fixed appliances were
      used as a basis for this study. Tooth movement was analysed on casts before (Ci)
      and after treatment (Cf). The casts were digitized either with a COMT or 3D laser
      scanning systems. After digitization, the models were superimposed in the palate
      by using a surface-surface matching algorithm. Tooth surfaces of the
      orthodontically moved teeth were segmented and determination of tooth movement
      was accomplished by matching the moved teeth from Ci to Cf. The resulting
      transformations delivered three dimensional information on translations and
      rotations. An accuracy of 0.2 mm in translations and 1 degree in rotations could
      be demonstrated, showing the different efficiency of treatment schemes.

PMID- 14675957
TI  - Whisking as a "voluntary" response: operant control of whisking parameters and
      effects of whisker denervation.
AB  - The rat's ability to vary its whisking "strategies" to meet the functional
      demands of a discriminative task suggests that whisking may be characterized as a
      "voluntary" behavior--an operant--and like other operants, should be modifiable
      by appropriate manipulations of response-reinforcer contingencies. To test this
      hypothesis we have used high-resolution, optoelectronic "real-time" recording
      procedures to monitor the movements of individual whiskers and reinforce specific
      movement parameters (amplitude, frequency). In one operant paradigm (N = 9)
      whisks with protractions above a specified amplitude were reinforced (Variable
      Interval 30 s) in the presence of a tone, but extinguished (EXT) in its absence.
      In a second paradigm (N = 3), rats were reinforced on two different VI schedules
      (VI-20s/VI-120s) signaled, respectively, by the presence or absence of the tone.
      Selective reinforcement of whisking movements maintained the behavior over many
      weeks of testing and brought it under stimulus and schedule control. Subjects in
      the first paradigm learned to increase responding in the presence of the tone and
      inhibit responding in its absence. In the second paradigm, subjects whisked at
      significantly different rates in the two stimulus conditions. Bilateral
      deafferentation of the whisker pad did not impair conditioned whisking or disrupt
      discrimination behavior. Our results confirm the hypothesis that rodent whisking
      has many of the properties of an operant response. The ability to bring whisking
      movement parameters under operant control should facilitate electrophysiological
      and lesion/behavioral studies of this widely used "model" sensorimotor system.

PMID- 14675958
TI  - Whisker motor cortex ablation and whisker movement patterns.
AB  - Previous studies, based on qualitative observations, reported that lesions of the
      whisker motor cortex produce no deficits in whisking behavior. We used high
      resolution optoelectronic recording methods to compare the temporal organization
      and kinematics of whisker movements before and after unilateral lesions of
      whisker motor cortex in rats. We now report that while the lesion did not abolish
      whisking, it significantly disrupted whisking kinematics, coordination, and
      temporal organization. Lesioned animals showed significant increases in the
      velocity and amplitude of whisker protractions contralateral to the lesions, as
      well as a reduction in the synchrony of whisker movements on the two sides of the
      face. There was a marked shift in the distribution of whisking frequencies, with
      reduction of activity in the 5-7 Hz bandwidth and increased activity at < 2 Hz.
      Disruptions of the normal whisking pattern were evident on both sides of the
      face, and the magnitude of these effects was proportional to the extent of the
      cortical ablation. We suggest that the observed deficits reflect an imbalance in
      cortical inputs to a brainstem central pattern generator.

PMID- 14675959
TI  - Correlation of spatial event plots with simulated population responses of
      mechanoreceptive fibers.
AB  - The experimental setup for generating spatial event plots (SEPs) from single
      mechanoreceptive fibers of the skin was computationally simulated. The generic
      fibers used in the simulations were similar to the rapidly adapting fibers (RAs),
      and had variable refractoriness and receptive-field size. The speed, lateral
      shift, and the contact width of the drum scanned across the receptive field of
      the fiber are adjustable parameters. The stimulus patterns used on the drum
      mimicked stimuli used by several other investigators. These were dot patterns,
      grating patterns, and the letter "E". First, the effects of simulation parameters
      on the SEPs were studied. The simulation output confirms the results of
      physiological experiments that SEPs contain information on the spatiotemporal
      resolution of the fiber. The next series of simulations involved generating SEPs
      of fibers obtained from the same or varying spatial distributions of receptive
      fields. Three hypothetical distributions were used: homogeneous rectangular,
      uniformly random, and Gaussian. The momentary population response at each case
      was found using the technique by Johansson and Vallbo (Brain Res 184: 353-366,
      1980). The population responses were not isomorphic images of the stimulus
      patterns due to the variations in field sizes and locations. However, every
      fiber, no matter which distribution it came from, generated almost identical SEPs
      given similar response properties. Furthermore, the SEPs looked like the outline
      of the stimulus. These observations show that SEPs do not contain information
      about the population response. Therefore, reconstructing the population response
      using SEPs can result in misleading conclusions on central-nervous-system
      processing and should be viewed cautiously when formulating
      psychophysical/physiological linking hypotheses.

PMID- 14675960
TI  - Distribution of trigeminothalamic and spinothalamic lamina I terminations in the
      cat.
AB  - The distribution in the thalamus of terminal projections from lamina I neurons of
      the trigeminal, cervical, and lumbosacral dorsal horn was investigated with the
      anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) in the cat.
      Iontophoretic injections were guided by single- and multi-unit physiological
      recordings. The injections in particular cases were essentially restricted to
      lamina I, whereas in others they spread across laminae I-III or laminae I-V. The
      trigemino- and spinothalamic (TSTT) terminations were identified
      immunohistochemically. In all cases, regardless of the level of the injections,
      terminal fibers were consistently distributed in three main locations: the
      submedial nucleus; the ventral aspect of the basal ventral medial nucleus and
      ventral posterior nuclei; and, the dorsomedial aspect of the ventral posterior
      medial nucleus. The terminal fields in the submedial nucleus and the ventral
      aspect of the ventral posterior group were topographically organized.
      Terminations along the ventral aspect of the ventral posterior group extended
      posterolaterally into the caudal part of the posterior nucleus and anteromedially
      into the ventromedial part of the ventral lateral nucleus. In several cases with
      trigeminal lamina I injections, a terminal labeling patch was observed within the
      core of the ventral posterior medial nucleus. In cases with spinal lamina I
      injections, terminations were also consistently found in the lateral habenula,
      the parafascicular nucleus, and the nucleus reuniens. Isolated terminal fibers
      were occasionally seen in the zona incerta, the dorsomedial hypothalamus, and
      other locations. These anatomical observations extend prior studies of TSTT
      projections and identify lamina I projection targets that are important for
      nociceptive, thermoreceptive, and homeostatic processing in the cat. The findings
      are consistent with evidence from physiological (single-unit and antidromic
      mapping) and behavioral studies. The novel identification of spinal lamina I
      input to the lateral habenula could be significant for homeostatic behaviors.

PMID- 14675961
TI  - Organization of Meissner corpuscles in the glabrous skin of monkey and cat.
AB  - Reconstructing neural-population responses in the form of spatial event plots
      assumes that the receptors are organized in a dense linear array. We have found
      that this assumption is not valid by determining the spatial organization of
      Meissner corpuscles (MCs) in the glabrous skin of both cat and monkey. The tissue
      was excised from animals that had been cardiac perfused with 4% paraformaldehyde.
      One-micrometer plastic sections revealed that the morphology of these receptors
      is different in the two animal species. However, in both species, they reside in
      approximately the same place in the dermal pegs of the skin, between the
      epidermal ridges, and electrophysiologically they both respond to ramp-and-hold
      stimuli with a rapidly adapting firing pattern. Thus, in this study we will refer
      to the receptors of the cat as "Meissner-like". In monkey, MCs are located in the
      dermal papillae between the epidermal limiting and intermediate ridges, forming
      orderly rows, the contours of which follow the overlying fingerprint. Although
      the average density of MCs is 45/mm2, they are distributed along the dermal pegs
      in such a manner as to give rise to three significantly ( p < 0.017) different
      average distances between corpuscles. We note that "fingerprints" vary in
      topography across the hand and this is also reflected in the underlying MC
      arrays. In the cat, these "Meissner-like" receptors display no specific pattern
      and have a density much lower than in the monkey. Cat glabrous skin does not have
      "fingerprints". The results emphasize that the spatial organization of tactile
      receptors must be taken into account when interpreting reconstructed population
      responses.

PMID- 14675962
TI  - Whisker plucking alters responses of rat trigeminal ganglion neurons.
AB  - Whisker plucking in developing and adult rats provides a convenient method of
      temporarily altering tactile input for the purposes of studying experience
      dependent plasticity in the somatosensory cortex. Yet, a comprehensive
      examination of the effect of whisker plucking on the response properties of
      whisker follicle-innervating trigeminal ganglion (NVg) neurons is lacking. We
      used extracellular single unit recordings to examine responses of NVg neurons to
      controlled whisker stimuli in three groups of animals: (1) rats whose whiskers
      were plucked from birth for 21 days; (2) rats whose whiskers were plucked once at
      21 days of age; and (3) control animals. After at least 3 weeks of whisker re
      growth, NVg neurons in plucked rats displayed normal, single whisker receptive
      fields and could be characterized as slowly (SA) or rapidly adapting (RA). The
      proportion of SA and RA neurons was unaffected by whisker plucking. Both SA and
      RA NVg neurons in plucked rats displayed normal response latencies and angular
      tuning but abnormally large responses to whisker movement onsets and offsets. SA
      neurons were affected to a greater extent than RA neurons. The effect of whisker
      plucking was more pronounced in animals whose whiskers were plucked repeatedly
      during development than in rats whose whiskers were plucked once. Individual
      neurons in plucked animals displayed abnormal periods of prolonged rhythmic
      firing following deflection onsets and aberrant bursts of activity during the
      plateau phase of the stimulus. These results indicate that whisker plucking
      exerts a long-term effect on responses of trigeminal ganglion neurons to
      peripheral stimulation.

PMID- 14675963
TI  - Temporal gap detection in tactile channels.
AB  - The ability of observers to detect temporal gaps in bursts of sinusoids or bursts
      of band-limited noise was measured to assess the temporal acuity of Pacinian (P)
      and non-Pacinian (NP) tactile information processing channels. The P channel was
      isolated by delivering high frequency sinusoids or high frequency noise through a
      large 1.5-cm2 contactor to the thenar eminence. The NP channels were isolated
      from the P channel by delivering these stimuli as well as stimuli with lower
      frequencies through a small 0.01-cm2 contactor to the same site. Gap detection
      thresholds were higher for gaps in noise than for gaps in sinusoids but did not
      differ among conditions designed to isolate P and NP channels. The finding that
      temporal acuity does not differ among channels supports the hypothesis that,
      after termination of a stimulus, the P and NP channels exhibit the same amount of
      neural persistence. Also consistent with this hypothesis are the earlier findings
      that the enhancement of the sensation magnitude of a stimulus by a prior stimulus
      (Verrillo and Gescheider, Percept Psychophys 18: 128-136, 1975) and the duration
      of sensation after the termination of a stimulus (Gescheider et al., J Acoust Soc
      Am 91: 1690-1696, 1992) are independent of stimulus frequency. One important
      implication of this hypothesis, if true, is that the presence of temporal
      summation in the P channel and its absence in the NP channels, results, not from
      the lack of neural persistence in the NP channels, but instead, in marked
      contrast to the P channel, from the lack of a mechanism for integrating
      persistent neural activity over time.

PMID- 14675964
TI  - Frequency responses of cat rapidly adapting mechanoreceptive fibers.
AB  - The frequency responses of 11 rapidly adapting (RA) fibers in cat were studied by
      representing the average firing rate as a function of sinusoidal stimulus
      amplitude and stimulus frequency. Specifically, rate-intensity functions at
      different stimulation frequencies were fitted by four-parameter (a0, a1, a2, a3),
      piece-wise linear functions using nonlinear regression (n = 59; R2 > 0.877). Rate
      intensity functions at intermediate frequencies were found by linear
      interpolation. The result of this analysis is rate-amplitude-frequency functions
      plotted as two-dimensional surfaces. The surfaces consist of five regions
      separated and sufficiently defined by four space curves. At 14 different
      frequencies, the statistical distribution of each rate-intensity-function
      parameter could be approximated by a particular lognormal distribution (n = 56;
      R2 > 0.796). The Kolmogorov-Smirnov test fails to reject this hypothesis for each
      combination of frequency and parameter (56 tests; p > 0.39). Therefore, at a
      given frequency, the variation of the parameters can be represented by lognormal
      distributions with specific means and standard deviations. Responses of six RA
      fibers, which are different from the data-set used for modeling, were compared
      with the stochastic model at different frequencies. The parameters of those
      fibers were tested against the null hypotheses that they were sampled from the
      particular parameter distributions dictated by the model. The Kolmogorov-Smirnov
      test fails to reject all the hypotheses at the alpha = 0.05 level (44 tests). At
      the alpha = 0.10 level, only a few test parameters were found to be departing
      from the model (a0 and a1 at 5 Hz; a2 at 20 Hz; a2 and a3 at 50 Hz). The
      remaining test parameters could be accurately described by the model. Having
      confirmed the validity of the model, the logarithmic means and the logarithmic
      standard deviations of the lognormally distributed rate-intensity-function
      parameters were estimated in the frequency range of 4-200 Hz. The rate-amplitude
      frequency surfaces sampled from the established stochastic model completely
      characterize the rate responses of RA fibers to sinusoidal stimuli and are
      superior to tuning curves which require selecting criterion responses. The
      current rate-response model is promising for future computational work,
      especially on population modeling.

PMID- 14675965
TI  - Localization and distribution of laminin in the basal lamina of certain
      mechanoreceptors--an immunogold study.
AB  - The applied immunogold cytochemical technique in investigating the cytologic
      distribution of the laminin (LAM) molecule in the capsulated Pacinian and Herbst
      mechanoreceptors shows the presence of LAM around most elements of the receptor
      structures. The LAM immunoreactivity (LAM-IR) is best expressed in the vicinity
      of the perineural capsule cells of both receptor types, where it is primarily
      concentrated around the perinuclear regions as well as the cytoplasmic lamellae.
      Such a localization overlaps with the already known ultrastructural localization
      of a basal lamina (BL) around these cells. Laminin immunoreactivity is less well
      expressed around the modified Schwann cells. Even in these cells, however, there
      is an apparent immunoreaction around the cytoplasmic lamellae regardless of the
      lamellar location. In both receptor types, there is no LAM-IR in the cells of the
      subcapsular space. Of particular significance we consider the localization of
      gold particles (respectively the presence of a BL) between the innermost lamellae
      of the modified Schwann cells and the non-myelinated part of the receptor nerve
      fiber and their endings, as well as around the axoplasmic protrusions of the
      nerve endings. We discuss the role of the BL and LAM in the investigated rapidly
      adapting mechanoreceptors and their trophic influence upon the sensory regions.
      We also assume the arresting and selective effect of these membranes in building
      up the ion channels of the axolemma which probably has a certain importance in
      mechanotransduction.

PMID- 14675966
TI  - Decline of tactile acuity in aging: a study of body site, blood flow, and
      lifetime habits of smoking and physical activity.
AB  - Tactile acuity of 60 older subjects (> or = 65 years) and 19 younger subjects (18
      28 years) was assessed by two-point gap thresholds at the upper and lower
      surfaces of the forefinger, at the upper and lower surfaces of the feet, and at
      the volar surface of the forearm. The older subjects were assigned to one of four
      groups of 15 subjects each, depending on reported lifetime habits of physical
      activity and smoking: (1) active smokers, (2) active nonsmokers, (3) inactive
      smokers, and (4) inactive nonsmokers. Peripheral blood flow was assessed at the
      forefinger, foot, and forearm by means of laser-Doppler imaging and skin
      temperature recordings, under resting conditions and during and after a 5-min
      exposure to mild cooling (28 degrees C). Consistent with previous studies,
      tactile acuity thresholds in the foot and finger averaged about 80% higher in the
      older subjects than in the younger subjects, but only about 22% higher in the
      forearm. Although the upper surface of the fingertip was more sensitive than the
      lower surface in both younger and older subjects, the age-related decline in
      tactile acuity was nearly identical on both sides of the finger and foot. The
      latter finding refutes the hypothesis that the larger effect of aging in the
      extremities results from greater physical wear and tear on the contact surfaces
      of the hands and feet. Self-reported lifetime histories of physical activity and
      smoking were not significantly associated with measures of cutaneous blood flow
      or tactile thresholds. Possible reasons for this lack of association are
      discussed, including the inherent limitations of testing only healthy older
      subjects, and the concept of "successful aging".

PMID- 14675967
TI  - Active knee joint velocity replication measures are stable and accurate in
      healthy individuals.
AB  - The purpose of this study was to determine the stability and accuracy of active
      knee joint velocity replication methods in healthy subjects. We used a repeated
      measures design with 14 healthy volunteers. Measures of velocity replication were
      performed in two ranges of knee joint flexion (0 degrees -30 degrees and 60
      degrees -90 degrees ), across four testing velocities (5, 10, 15, and 30 degrees
      /s) in two movement directions (flexion and extension). Statistical analysis
      included intraclass correlation coefficients (ICCs; 2, k) and associated standard
      error of the measures calculated between day 1 and 2. We performed z-tests
      between all possible combinations of ICC pairs using Fisher's Z transformations
      to determine if any significant differences existed between observed ICCs. We
      also calculated correlation ratios (eta2) to explain the source of variability in
      the calculated ICCs. To assess measurement accuracy, we calculated constant error
      and absolute error between criterion and replication velocities. Results on ICCs
      and standard error of the measurements (SEMs) ranged from r = -0.44 +/- 7.00 to
      0.88 +/- 0.72 degrees /s. Calculated z-tests indicated six paired ICCs were
      significantly different ( p < 0.1). In all six pairs, the faster test velocity
      had a lower ICC magnitude. The eta2 calculations demonstrated that inconsistent
      performance between day 1 and 2 caused the low ICC magnitudes observed with
      faster testing velocities. Significantly more absolute error occurred at 30 and
      15 degrees /s compared with 5 degrees /s. Significantly less constant error was
      observed for 30 degrees /s compared with 15 degrees /s. A significant direction
      by range of motion interaction indicated less constant error for flexion
      movements in the 60 degrees -90 degrees range of motion (ROM) as compared with
      extension movements in either ROM. Healthy individuals could actively replicate
      slower criterion velocities in the mid and end ranges of knee joint motion in
      both movement directions with an acceptable amount of consistency and accuracy.
      The data support the use of velocity replication in future investigations on
      proprioceptive function.

PMID- 14675969
TI  - Proceedings of the Barrels II Workshop: thalamocortical/corticothalamic loops.

PMID- 14675970
TI  - Proceedings of the Barrels II Workshop: cortical circuits.
AB  - The second session of the Barrels II Workshop focused on the function of cortical
      circuitry in the rodent vibrissa-to-barrel system. The session began with talks
      by Asaf Keller (University of Maryland), Christopher Moore (MIT), and David Pinto
      (Brown University). These presentations were followed by shorter talks by Mark
      Andermann (MIT), Alison Barth (Carnegie-Mellon University), Dirk Feldmeyer (Max
      Planck Institute), Cathy Garabedian (UCSF), Garrett Stanley (Harvard University),
      and Simona Temereanca (University of Pittsburgh). Presentations covered several
      central themes, including the functional organization of cortical circuitry,
      thalamocortical response transformations, temporal response properties, and the
      role of vibrissa resonance in high frequency representations. For simplicity,
      this review is organized by these central themes and does not follow the order of
      presentations at the meeting.

PMID- 14675971
TI  - Proceedings of the Barrels II Workshop: sensorimotor loops.
AB  - Rodents use their whiskers to explore their environment and to make very fine
      discriminations in textures and sizes of objects. Exploratory "whisking"
      movements consist of large amplitude, rhythmic whisker protractions that occur at
      characteristic frequencies of 5-10 Hz. Rodents likely whisk to move their
      receptor surface over the object they are touching. A fundamental understanding
      of this important motor behavior and the sensorimotor loops that control it were
      the focus of the final session of the Barrels Workshop. This session began with
      talks from David Kleinfeld (University of California San Diego), Miguel Nicolelis
      (Duke University), and Jonathan Rubin (University of Pittsburgh). These talks
      were followed by short presentations from Steven Leiser (Drexel University),
      Marcin Szwed (Weitzman Institute), Ford Ebner (Vanderbilt University), Charles
      Pluto (Medical College of Ohio), and Elisabeth Foeller (Washington University).

PMID- 14675972
TI  - The impact of maternal mortality interventions using traditional birth attendants
      and village midwives.
AB  - Traditional birth attendants (TBAs) and village midwives have been employed in
      many interventions to reduce maternal mortality in developing countries. This
      study reviews the results of 15 TBA- and midwife-based interventions that aim to
      improve skilled assistance in delivery and recognition and referral of
      complications. Outcome measures used to evaluate the impact of the programmes
      varied. Five of the five programmes reviewed that evaluated their impact on
      maternal mortality demonstrated a decline in maternal mortality ratios, two of
      three studies measuring morbidity-related indicators found improvement of some
      but not all morbidity outcomes, six of seven showed a trend of improved referral
      rates, and three of three found high levels of knowledge retention among trained
      TBAs. Programmes with the greatest impact utilised TBAs and village midwives
      within multisectoral interventions. These findings suggest that TBAs and village
      midwives contribute to positive programme outcomes. Further investigation is
      needed to determine the nature of their contribution within larger programmes.

PMID- 14675973
TI  - The impact of induced labour on postpartum blood loss.
AB  - It is generally believed that postpartum blood loss is less in patients whose
      labour is induced with prostaglandins than in patients delivered without
      induction. However, postpartum blood loss is known to be greater with precipitate
      labour and labours induced with oxytocin and prostaglandins, unless an oxytocic
      agent is continued after delivery. A retrospective study was undertaken at the
      University Hospital of the West Indies to look at the outcome of induced labour
      during 3 months, October-December 1998. Misoprostol induction was compared to the
      outcome after oxytocin induction, misoprostol induction plus oxytocin
      augmentation and those patients who delivered without oxytocics during this same
      time period. During that period, 524 patients were delivered and 51 (9.7%) were
      induced with misoprostol, 174 (33.2%) with oxytocin, 21 (4%) misoprostol plus
      oxytocin and 271 (51.7%) without oxytocic. Seven patients were eliminated from
      further analysis, as we were unsure of their induction status. Results showed no
      significant differences between the groups for variables such as maternal age,
      parity and fetal birth weight. There was a significantly greater mean blood loss
      at delivery with all induced labour compared with those not induced. For
      misoprostol 162.5(SD 190) ml, oxytocin (150 (SD 100) ml and for oxytocin plus
      misoprostol 150 (SD 150) ml, while controls had the lowest mean blood loss 100
      (SD 130) ml occurring where no predelivery oxytocic was needed (P<0.03).
      Postpartum haemorrhage was highest with misoprostol 5.8% versus 4.4% for no
      oxytocic, 1.1% for oxytocin and 0% for misoprostol plus oxytocin. However, none
      of these values reached statistical significance. The misoprostol group also had
      the shortest first stage, 333 minutes versus 557 minutes for oxytocin, 576
      minutes when both misoprostol and oxytocin was used and 344 minutes with no
      oxytocic. Blood loss was also independently directly associated with placental
      weight (P=0.01) and fetal birth weight (P=0.03), as well as the length of the
      third stage of labour (P=0.01), but not the length of the first stage of labour.
      Induction of labour with oxytocic agents is associated with greater blood loss.
      However, increased blood loss is not due to precipitate labour alone.

PMID- 14675974
TI  - Impact of maternal anaemia on birth outcomes of teen twin pregnancies: a
      comparative analysis with mature young mothers.
AB  - We investigated the impact of maternal anaemia on birth outcomes among adolescent
      twin pregnancies in the United States using the vital statistics records for
      matched multiple births covering the years 1995-1997 inclusive. The study group
      consisted of mothers aged 19 years or younger who had a twin pregnancy. A cohort
      of women aged 20-29 years with twin pregnancies served as the comparison group.
      The main birth outcomes of interest were: low and very low birth weight, preterm
      and very preterm delivery, small-for-gestational age, stillbirth, neonatal and
      perinatal mortality. Crude and adjusted odds ratios for the above outcomes were
      calculated using the generalised estimating equation framework (GEE) that
      captured both intra- and intercluster sources of heterogeneity. Although not
      statistically significant, we detected an elevated risk for stillbirth among
      anaemic women (20-30%) in either age cohort, a magnitude that is substantial at
      the population level as well as warranting further aetiological investigations.

PMID- 14675975
TI  - Urinary tract infection during pregnancy--dipstick urinalysis vs. culture and
      sensitivity.
AB  - Although it is important not to ignore clinical symptoms suggestive of a urinary
      tract infection (UTI), especially in antenatal patients, samples which have no
      abnormalities detected on bedside urinalysis may not need to be sent to the
      laboratory for culture and sensitivity (C&S) testing. If leucocytes, blood and/or
      protein are found in the samples, then they may need to be sent to the laboratory
      for further assessment, but no treatment needs to be instigated before obtaining
      the culture and sensitivity result, unless indicated clinically. The presence of
      nitrites in the sample is, however, much more suggestive of a bacterial infection
      and samples must be sent to the laboratory. In these cases, treatment with
      antibiotics prior to results may be warranted. Of the 100 samples tested in this
      study, only two had positive cultures for bacterial infection (Escherichia coli)
      and these were the only samples which had been strongly positive for nitrites
      using the Nephrur6Labsticks. These bedside screening tests may be a useful and
      cost-effective way of reducing the numbers of mid-stream urine samples sent to
      the laboratory for further testing.

PMID- 14675976
TI  - The outcome of pregnancy after large loop excision of the transformation zone of
      the cervix.
AB  - A retrospective case control study to assess the outcome of pregnancy after large
      loop excision of the transformation zone of cervix (LLETZ) was carried out. One
      hundred and nineteen women who had undergone LLETZ and delivered in Basildon
      District Hospital were identified between January 1995 and December 1998; 119 age
      and parity-matched controls were selected. Variables included were miscarriages,
      preterm deliveries, gestation at delivery, onset of labour, length of labour,
      augmentation of labour, mode of delivery and birth weight. The miscarriage rate
      in the study and control group were 11.8% and 9.2%, respectively (P=0.53). The
      preterm delivery rate in the study and control group were 10.9% and 9.2%,
      respectively (P=0.67). There were fewer caesarean sections and more spontaneous
      vaginal deliveries in the study group. There were slightly more instrumental
      deliveries in the study group. From this study, it was concluded that LLETZ does
      not appear to have an adverse effect on the outcome of pregnancy.

PMID- 14675977
TI  - Psychological health in early pregnancy: relationship with nausea and vomiting.
AB  - The psychological health of women in early pregnancy was investigated in a sample
      of 273 women (mean gestational age 12.8 weeks, SD=2.8) using the General Health
      Questionnaire (GHQ) and mood and illness perception visual analogue scales, and
      compared with the prevalence and severity of nausea and vomiting as measured
      using the Nausea and Vomiting in Pregnancy Instrument (NVPI). Using a cut-off of
      4/5 for the GHQ, 50.5% of pregnant women were found to have potential psychiatric
      problems. However, perceived mental health and physical illness was significantly
      better than anticipated. The severity of nausea and vomiting correlated
      independently with GHQ subscales for somatic symptoms, social dysfunction,
      anxiety/insomnia and severe depression. The contradiction between high GHQ scored
      and high perceived wellbeing might be explained through cognitive processing.
      Nausea and vomiting in early pregnancy is associated with psychiatric morbidity.
      The causal relationship between the two conditions has not been established.

PMID- 14675978
TI  - A questionnaire study of women's views regarding the effectiveness of serum Down
      screening in north west Wales.
AB  - Questionnaires were circulated to 300 women awaiting mid-trimester anomaly
      scanning in north west Wales to determine women's views of the adequacy of
      counselling, availability of pretest scanning, method of receiving test results
      and whether the Down screening process in general was acceptable. Seventy-five
      per cent of respondents had serum Down screening; 80.3% of women agreed or
      strongly agreed that counselling prior to antenatal testing for Down syndrome was
      adequate; 80.7% of women agreed or strongly agreed that the consequences of a
      high risk result were explained before testing; 88.7% of women agreed or strongly
      agreed that they had a choice as to whether screening was accepted or not; 81.7%
      of women agreed or strongly agreed that they were involved in the decision
      process; and 40.0% of women having Down testing did not have previous ultrasound
      biometry. Routine pretest ultrasound scanning remains a resource priority.

PMID- 14675979
TI  - Trends in maternal mortality due to haemorrhage: two decades of Indian rural
      observations.
AB  - Obstetric haemorrhage continues to be a major cause of maternal mortality. Our
      analysis of records of over a period of 20 years from April 1982 to March 2002
      reveals that it was a contributory cause of maternal mortality in 19.9% of cases.
      The majority of deaths, (65%) had occurred within 24 hours of admission and in
      47.5% of cases there was severe anaemia on admission; 17.5% had died due to an
      atonic PPH, which was the largest category, followed by ruptured uterus (15%),
      abruptio placenta (15%) and retained placenta (12.5%). Deaths due to obstetric
      haemorrhage because of a ruptured uterus, retained placenta and abortion have
      decreased from 22.22% between 1982 and 1987 to zero in the last 5 years and an
      increase was seen in deaths due to haemorrhage because of gestational
      trophoblastic neoplasia and ectopic pregnancy, from 1.69% to 4.87%, unclassified
      haemorrhage 1.96% to 7.31% and placenta praevia from zero between 1982 and 1987
      to 4.87% between 1997 and 2002.

PMID- 14675980
TI  - Audit: women's perception and knowledge of the 20 weeks anomaly scan.
AB  - We surveyed 385 women attending two maternity units for an anomaly scan at 20
      weeks' gestation. Ninety-five per cent of the women thought that the purpose of
      the anomaly scan was to check for structural abnormalities in the fetus,
      indicating good knowledge. Most women thought the anomaly scan would pick up
      spinal, limb and kidney abnormalities. There was high expectation of what
      structural abnormalities the anomaly scan could pick up; 22% and 51% of the women
      thought the scan would pick up 61-70% and 71-100% of the structural
      abnormalities, respectively. Only 8% of the women thought, realistically, that
      the anomaly scan would pick up 50% of the abnormalities. The women's knowledge of
      soft markers was poor; 92% of them never heard of it. The main source of
      information about the anomaly scan was the hospital.

PMID- 14675981
TI  - Raloxifene inhibits cholesterol aortic content but not atherosclerotic plaque
      size in oophorectomised cholesterol-fed rabbits.
AB  - Raloxifene, a selective oestrogen receptor modulator, is effective in the
      treatment of osteoporosis without stimulating the breast and the endometrium.
      Although it is associated with a decrease of cardiovascular risk markers the
      effect of these changes on atherogenesis, is not clear. In this study, we aimed
      to investigate the effect of raloxifene on aorta atherogenesis. A total of 32
      cholesterol-fed New Zealand white rabbits were studied for 4 months. Twenty-four
      rabbits underwent bilateral ovariectomy; of these eight received raloxifene
      (group OR), eight received oestradiol valerate (group OE) and eight received
      placebo after sterilisation (group OP). Finally, another eight were sham-operated
      (non-ovariectomised) and received placebo with a hypercholesterolaemic diet
      (group SP). After the diet, total levels of cholesterol increased in group SP
      from 111.25 +/- 34.8 mg/dl to 1112.25 +/- 364.2, in group OP from 122.62 +/- 27.7
      mg/dl to 1367.37 +/- 348.4, in group OE from 65.25 +/- 17.01 to 1710.5 +/- 356.2
      and in group OR from 108.88 +/- 15.54 mg/dl to 1407.86 +/- 397.7 (no significant
      differences). At 4 months, in both treated and untreated rabbits, the cholesterol
      rich diet caused atherosclerotic lesions affecting 24.51 +/- 16.1% for group SP,
      30.47 +/- 12.2% for group OP, 30.31 +/- 18.07% for group OR and 17.91 +/- 10.19
      for group OE (P<0.05) of the aortic surface, respectively. Aortic cholesterol
      expressed as mg of cholesterol/mg aortic weight was found to decrease in
      raloxifene-treated rabbits: 3.82 +/- 2.14 mg col/aortic mg versus 8.55 +/- 4.63
      (group OP) and 11.97 +/- 11.33 (group SP). P<0.001. Raloxifene reduced aortic
      cholesterol content but not the atherosclerotic plaque extension in cholesterol
      fed ovariectomised rabbits.

PMID- 14675982
TI  - Comparative analysis of oestrogen and raloxifene effects on the phospholipid
      composition of high density lipoproteins in healthy postmenopausal women.
AB  - The beneficial effect of selective oestrogen receptor modulators such as
      raloxifene in cardiovascular disease may be mediated partly by favourable changes
      in the phospholipid composition of high density lipoprotein (HDL) subclasses. In
      Group A (oestrogen alone) HDL2 phosphatidylcholine increased (P<0.001), while
      there was a decrease in HDL2 phosphatidylinositol (P<0.05) and HDL2
      phosphatidylethanolamine (P<0.05) compared to controls (baseline). In the same
      group, HDL3 phosphatidylcholine increased (P<0.001) and HDL3
      phosphatidylethanolamine decreased (P<0.01). In Group B (raloxifene) HDL2
      phosphatidylcholine increased (P<0.001) as well as HDL2 diphosphatidylglycerol
      (P<0.01) while there were decreases in HDL2 sphingomyelin (P<0.01) and HDL2
      phosphatidylethanolamine (P<0.05). In the same group, an increase in HDL3
      phosphatidylcholine (P<0.001) and a reduction in HDL3 phosphatidylinositol
      (P<0.05) were observed as well as a decrease in HDL3 phosphatidylethanolamine
      (P<0.01) and HDL3 diphosphatidylglycerol (P<0.05). The significance of these
      results is discussed.

PMID- 14675983
TI  - Current causes and management of violence against women in Nigeria.
AB  - Violence against women is an important health and human rights issue. It carries
      with it both short- and long-term sequelae for women that can affect both their
      physical and psychological wellbeing. Every day obstetric providers treat
      patients who have been assaulted. Timely identification can interrupt the cycle
      of violence, prevent further injury and initiate the help-seeking process. The
      objectives of this study were to survey how often Nigerian obstetrician
      gynaecologists see these patients in their practice and to describe the
      demographics and management of their most recent case so as to give an idea of
      the extent of the problem. This is especially important as abuse is grossly under
      reported because the victims are afraid to report it because of male dominance in
      society and the fear of losing their homes. We used a self-administered
      questionnaire survey of 138 practising obstetricians and gynaecologists in
      Nigeria. Questions were asked about the yearly estimation of cases seen and how
      recently a case was seen. The type of abuse, risk factors and management of their
      most recent case was also documented. Most (98.6%) obstetricians surveyed had
      previously managed a case of violence. The mean estimate of abused women seen was
      7.0 per year. Details of the last case managed were recollected by 91.3% of
      respondents. The majority (51.6%) of patients were pregnant. The assailant was
      the husband in 69.8% of cases and the most common factor for abuse was as a
      result of women requesting money for the family needs from their husbands. The
      most common type of abuse was physical (79.4%), with 34.9% of patients sustaining
      cuts. Treatment and counselling were the forms of management in most cases. The
      police were informed in 9.5% of cases and one obstetrician had to give evidence
      in court. Of the pregnant abused women, 73.8% had live births. Better job
      opportunities and female empowerment can reduce the risk of violence.
      Obstetricians should screen routinely for battery, provide education about
      violence, assess the danger, review safety plans and refer women appropriately.
      We cannot solve the problem alone, but sensitivity and commitment can begin to
      make a difference.

PMID- 14675984
TI  - The effect of a gonadotrophin-releasing hormone analogue as first-line management
      in cyclical pelvic pain.
AB  - One of the most common gynaecological causes of chronic pelvic pain is
      endometriosis. A lack of correlation between laparoscopic findings and pelvic
      pain has been reported. As endometriotic lesions are under hormonal influence,
      the effects of the gonadotrophin-releasing hormone (GnRH) analogues cause
      shrinkage of the deposits, reducing symptoms caused by them. We carried out a
      longitudinal, interventional pilot study, examining the effect of leuprorelin
      acetate 3.75 mg (Prostap SR, Wyeth) on pelvic pain prospectively. Preliminary
      data shows a decrease in pain scores from before to after treatment which is
      statistically significant (P<0.0001) as well as a general improvement in other
      symptoms. Laparoscopy showed that symptom intensity is not always related to
      severity of endometriosis and the worst symptoms may not necessarily be due to
      pathology. Therefore, it is beneficial to treat women with CPP with GnRH
      analogues as first-line management to relieve painful symptoms, avoid surgical
      risks and save money.

PMID- 14675985
TI  - Medical management of first trimester incomplete miscarriage using misoprostol.
AB  - This prospective study looked at the effectiveness of 400 microg oral misoprostol
      in the management of women with a first trimester incomplete miscarriage with
      retained products of conception measuring between 15 mm and 50 mm on transvaginal
      ultrasound scan. Of 164 eligible women, 131 agreed to participate. Successful
      treatment, defined as an empty uterus on scan after 10 days with no bleeding, was
      achieved in 77.7% of women. Some women with retained products opted to have
      further misoprostol or conservative management instead of surgical evacuation and
      in total 92.4% of women completed their miscarriage without requiring surgery.
      Most bleeding was mild (31.3%) to moderate (38.9%), lasting on average 6.4 days.
      Forty-five per cent of women needed no pain relief, 51% received oral analgesia
      and 4% intramuscular opiates. Adverse effects included nausea (10.93%), diarrhoea
      (2.34%), vomiting (7.8%) and hypotension (4.68%). There were no infections. We
      concluded that a single dose of 400 microg of oral misoprostol was an effective
      treatment for women presenting with an incomplete miscarriage.

PMID- 14675986
TI  - Medical management of first trimester miscarriage (blighted ovum and missed
      abortion): is it effective?
AB  - This prospective study of 104 women investigated the dose-related efficacy of
      mifepristone combined with oral misoprostol in the management of first trimester
      miscarriage (missed abortion and blighted ovum). Forty-four women (group A)
      received 600 mg of oral mifepristone and 60 women (group B) received 200 mg of
      mifepristone, followed after 48 hours by oral misoprostol. Successful treatment
      was an empty uterus on scan and no bleeding after 10 days. This was achieved in
      70.5% of group A and 66.7% of group B. Also studied were amount and time to
      cessation of bleeding, pain scores, analgesic requirements, adverse effects and
      infections. Of group A, 54.5% had heavy bleeding and bleeding stopped on average
      by 8 days. Median pain scores were 5.5 on a linear scale and 18% of women
      received intramuscular opiate analgesia. Adverse effects were nausea in 25% of
      women and diarrhoea in 16%. Of group B, 38.3% had heavy bleeding and bleeding
      stopped on average by 7 days. Median pain scores were 4.5 with 25% of women
      receiving intramuscular opiates. Nausea occurred in 7% of women and diarrhoea in
      7%. We concluded that 200 mg of mifepristone and oral misoprostol is as effective
      and better tolerated than 600 mg mifepristone with oral misoprostol. Medical
      management of miscarriage is a valid option for those women seeking an
      alternative to traditional surgical management.

PMID- 14675987
TI  - Hysterectomy for abnormal cervical cytology following treatment for cervical
      intra-epithelial neoplasia.

PMID- 14675988
TI  - Chromatin fluorescence characteristics and standard semen analysis parameters:
      correlations observed in andrology testing among 136 males referred for
      infertility evaluation.
AB  - This paper aims to describe the relation between standard semen analysis
      parameters (concentration, motility and morphology) and sperm chromatin structure
      assay (SCSA) results among patients referred for infertility evaluation. Healthy
      males (n=136) seeking infertility consultation were evaluated prospectively by
      semen analysis and sperm chromatin structure assay (SCSA). Significant inverse
      correlations were observed between high sperm concentration and DNA fragmentation
      index (DFI) and high DNA stainability (HDS) (r=- 0.45; P<0.001, and r=- 0.40;
      P<0.001, respectively). Both progressive motility and normal morphology were also
      strongly inversely correlated with DFI and HDS. However, in stratified analysis
      the correlation between concentration < or =20 M/ml and DFI, and concentration <
      or =20 M/ml and HDS were not significant (P=0.31 and 0.38, respectively). For men
      with sperm motility < or =40% the correlation between motility and HDS was not
      significant (P=0.22), but between motility and DFI the correlation remained
      significant (P=0.04). Although strong correlations between DFI, HDS and semen
      analysis findings were noted in the overall study population, when
      oligozoospermic and asthenozoospermic patients were analysed separately the
      correlation between concentration and sperm chromatin fragmentation was not
      significant. For such men, SCSA appears to be a diagnostic variable independent
      of the semen analysis, providing information about nuclear abnormalities not
      readily apparent from standard semen analysis alone. Additionally, SCSA data may
      offer explanations for previous miscarriage, providing closure for some couples
      contemplating future use of anonymous donor sperm.

PMID- 14675989
TI  - Overseas registrars training in obstetrics and gynaecology in Wales--a
      questionnaire survey.
AB  - Overseas doctors have been coming to the United Kingdom for further surgical
      training over the past several years. In Wales, up to 50% of registrars in
      obstetrics and gynaecology are from overseas. It is important to address issues
      regarding training with a view to making changes and improvements to suit
      individual trainee requirements. There is very little evidence obtained from
      literature regarding trainees' viewpoints, satisfaction, achievements and
      expectations with regard to overseas registrars in obstetrics and gynaecology. We
      undertook a questionnaire survey assessing the training of all overseas
      registrars in Wales from 12 hospitals in the Deanery. The results of this survey
      are discussed in the article with a few suggestions for change.

PMID- 14675990
TI  - Computer skills among trainee doctors.
AB  - Computer skills are an essential part of every field, including medicine.
      However, training in computers is limited mainly to clerical and paramedical
      staff. We conducted this questionnaire survey to assess the extent of training
      and the opinion of trainee doctors in obstetrics and gynaecology in Wales. The
      results showed that the computer skills among these doctors was low and the
      majority of them agreed that there was a need for training in computer skills to
      assist them in their career progress. In view of the findings of this survey, we
      feel that incorporation of computer skills courses in the training curriculum
      must be of benefit.

PMID- 14675991
TI  - Paroxysmal nocturnal haemoglobinuria in pregnancy--not to be confused with pre
      eclampsia or HELLP syndrome. Case report and literature review.

PMID- 14675992
TI  - Successful pregnancy following two uterine artery embolisation procedures for
      arteriovenous malformation.

PMID- 14675993
TI  - Necrotising fasciitis following a caesarean section.

PMID- 14675994
TI  - A case of fetal pericardial effusion in association with maternal hypertension
      and HIV infection.

PMID- 14675995
TI  - An unusual presentation of meconium peritonitis.

PMID- 14675996
TI  - Papillary thyroid carcinoma of struma ovarii.

PMID- 14675997
TI  - Massive ovarian mucinous cystadenoma in a 14-year-old girl.

PMID- 14675998
TI  - Vulva haemangiopericytoma: case report and literature review.

PMID- 14675999
TI  - Recurrent vulval fibroids--an unusual indication for selective oestrogen receptor
      modulators (SERMs).

PMID- 14676000
TI  - Delayed vaginal erosion of the tape--a rare complication with TVT.

PMID- 14676001
TI  - Clitoral inclusion cyst: a complication of type I female genital mutilation.

PMID- 14676002
TI  - Primary carcinoid tumours of the ovary.

PMID- 14676003
TI  - Laparoscopic presentation of a rib chondroma.

PMID- 14676004
TI  - When can I drive, Doc?

PMID- 14676007
TI  - Severe acute respiratory syndrome vaccine development: experiences of vaccination
      against avian infectious bronchitis coronavirus.
AB  - Vaccines against infectious bronchitis of chickens (Gallus gallus domesticus)
      have arguably been the most successful, and certainly the most widely used, of
      vaccines for diseases caused by coronaviruses, the others being against bovine,
      canine, feline and porcine coronaviruses. Infectious bronchitis virus (IBV),
      together with the genetically related coronaviruses of turkey (Meleagris
      gallopovo) and ring-necked pheasant (Phasianus colchicus), is a group 3
      coronavirus, severe acute respiratory syndrome (SARS) coronavirus being
      tentatively in group 4, the other known mammalian coronaviruses being in groups 1
      and 2. IBV replicates not only in respiratory tissues (including the nose,
      trachea, lungs and airsacs, causing respiratory disease), but also in the kidney
      (associated with minor or major nephritis), oviduct, and in many parts of the
      alimentary tract--the oesophagus, proventriculus, duodenum, jejunum, bursa of
      Fabricius, caecal tonsils (near the distal end of the tract), rectum and cloaca
      (the common opening for release of eggs and faeces), usually without clinical
      effects. The virus can persist, being re-excreted at the onset of egg laying (4
      to 5 months of age), believed to be a consequence of the stress of coming into
      lay. Genetic lines of chickens differ in the extent to which IBV causes mortality
      in chicks, and in respect of clearance of the virus after the acute phase. Live
      attenuated (by passage in chicken embryonated eggs) IBV strains were introduced
      as vaccines in the 1950s, followed a couple of decades later by inactivated
      vaccines for boosting protection in egg-laying birds. Live vaccines are usually
      applied to meat-type chickens at 1 day of age. In experimental situations this
      can result in sterile immunity when challenged by virulent homologous virus.
      Although 100% of chickens may be protected (against clinical signs and loss of
      ciliary activity in trachea), sometimes 10% of vaccinated chicks do not respond
      with a protective immune response. Protection is short lived, the start of the
      decline being apparent 9 weeks after vaccination with vaccines based on highly
      attenuated strains. IBV exists as scores of serotypes (defined by the
      neutralization test), cross-protection often being poor. Consequently, chickens
      may be re-vaccinated, with the same or another serotype, two or three weeks
      later. Single applications of inactivated virus has generally led to protection
      of <50% of chickens. Two applications have led to 90 to 100% protection in some
      reports, but remaining below 50% in others. In practice in the field, inactivated
      vaccines are used in laying birds that have previously been primed with two or
      three live attenuated virus vaccinations. This increases protection of the laying
      birds against egg production losses and induces a sustained level of serum
      antibody, which is passed to progeny. The large spike glycoprotein (S) comprises
      a carboxy-terminal S2 subunit (approximately 625 amino acid residues), which
      anchors S in the virus envelope, and an amino-terminal S1 subunit (approximately
      520 residues), believed to largely form the distal bulbous part of S. The S1
      subunit (purified from IBV virus, expressed using baculovirus or expressed in
      birds from a fowlpoxvirus vector) induced virus neutralizing antibody. Although
      protective immune responses were induced, multiple inoculations were required and
      the percentage of protected chickens was too low (<50%) for commercial
      application. Remarkably, expression of S1 in birds using a non-pathogenic fowl
      adenovirus vector induced protection in 90% and 100% of chickens in two
      experiments. Differences of as little as 5% between the S1 sequences can result
      in poor cross-protection. Differences in S1 of 2 to 3% (10 to 15 amino acids) can
      change serotype, suggesting that a small number of epitopes are immunodominant
      with respect to neutralizing antibody. Initial studies of the role of the IBV
      nucleocapsid protein (N) in immunity suggested that immunization with bacterially
      expressed N, while not inducing protection directly, improved the induction of
      protection by a subsequent inoculation with inactivated IBV. In another study,
      two intramuscular immunizations of a plasmid expressing N induced protective
      immunity. The basis of immunity to IBV is not well understood. Serum antibody
      levels do not correlate with protection, although local antibody is believed to
      play a role. Adoptive transfer of IBV-infection-induced alphabeta T cells bearing
      CD8 antigen protected chicks from challenge infection. In conclusion, live
      attenuated IBV vaccines induce good, although short-lived, protection against
      homologous challenge, although a minority of individuals may respond poorly.
      Inactivated IBV vaccines are insufficiently efficacious when applied only once
      and in the absence of priming by live vaccine. Two applications of inactivated
      IBV are much more efficacious, although this is not a commercially viable
      proposition in the poultry industry. However, the cost and logistics of multiple
      application of a SARS inactivated vaccine would be more acceptable for the
      protection of human populations, especially if limited to targeted groups (e.g.
      health care workers and high-risk contacts). Application of a SARS vaccine is
      perhaps best limited to a minimal number of targeted individuals who can be
      monitored, as some vaccinated persons might, if infected by SARS coronavirus,
      become asymptomatic excretors of virus, thereby posing a risk to non-vaccinated
      people. Looking further into the future, the high efficacy of the fowl adenovirus
      vector expressing the IBV S1 subunit provides optimism for a live SARS vaccine,
      if that were deemed to be necessary, with the possibility of including the N
      protein gene.

PMID- 14676008
TI  - Increased lymphocyte subpopulations and macrophages in the ovaries and oviducts
      of laying hens infected with Salmonella enterica serovar Enteritidis.
AB  - Salmonella enterica serovar Enteritidis (SE) is a causative agent for human food
      poisoning cases throughout the world. The ovaries and the oviducts of the laying
      hens are the major sites of SE colonization from which vertical transmission to
      eggs occurs. In this study, Salmonella-induced changes in T lymphocytes, B
      lymphocytes and macrophages in the ovaries and oviducts were assessed after
      primary and secondary experimental inoculations of laying hen with SE.
      Statistically significant increases in the numbers of T cells (both CD4+ and
      CD8+) and macrophages were observed 7 to 14 days after primary inoculation,
      followed by a peak in B-cell numbers from the 14th day post-primary inoculation
      onwards in the secretory areas of the oviducts. The peak in lymphocyte numbers
      immediately preceded a decline in the rate of SE recovery from the reproductive
      tract beginning at day 14. The correlation of decreased Salmonella recovery with
      elevated lymphocyte and macrophage numbers strongly suggests that local cell
      mediated immunity is involved in controlling SE injection in the ovaries and
      oviducts.

PMID- 14676009
TI  - Tissue tropism in the chicken embryo of non-virulent and virulent Newcastle
      diseases strains that express green fluorescence protein.
AB  - The tissue tropism of non-virulent and virulent Newcastle disease virus (NDV) was
      investigated using 8-day-old and 14-day-old embryonating chicken eggs (ECE),
      inoculated with an infectious clone of the non-virulent La Sota strain (NDFL-GFP)
      or its virulent derivative (NDFLtag-GFP). Both strains expressed the gene
      encoding jellyfish green fluorescence protein (GFP) as a marker. The GFP was
      readily expressed in chicken embryo cells infected with the NDV strains
      indicating virus replication. Whereas both strains replicated in the
      chorioallantoic membrane (CAM) and infected the skin of 8-day-old ECE, only the
      virulent strain (NDFLtag-GFP) spread to internal organs (pleura/peritoneum). In
      14-day-old ECE, the initial target organs appeared to be the CAM and the lungs
      for both strains. At 48 h after inoculation, the virulent strain (NDFLtag-GFP)
      had also spread to the spleen and heart and was detected in a wide-range of
      embryonic cell types. The kinetics of virus replication and spread in the CAM
      closely resembled each other in both the 8-day-old and 14-day-old ECE. Infection
      of 8-day-old and 14-day-old ECE forms a convenient model to investigate tissue
      tropism of NDV, as well as the kinetics of viral infection. The advantage of
      using GFP is that samples can be easily screened by direct fluorescence
      microscopy without any pre-treatment.

PMID- 14676010
TI  - Protection from infectious bursal disease virus (IBDV)-induced immunosuppression
      by immunization with a fowlpox recombinant containing IBDV-VP2.
AB  - Immunosuppression resulting from infectious bursal disease virus (IBDV) infection
      has critical health and welfare implications for birds, yet it is incompletely
      understood and largely overlooked as a measure of vaccine efficacy. The ability
      of a fowlpoxvirus recombinant (fpIBD1) containing the VP2 protein of IBDV to
      protect against IBDV-induced immunosuppression was investigated by measuring the
      convalescent chicken's ability to mount antibody responses to IBDV infection, and
      to inactivated IBDV and salmonella vaccines. An immunoglobulin (Ig)M response,
      but no IgG response, occurred after IBDV infection. Uninfected chickens produced
      a sustained IgM response and some IgG response to inactivated IBDV vaccine, while
      in previously infected birds only a transient IgM response was detected. A
      moderate suppression of the response to a commercial salmonella vaccine was
      evident after IBDV infection, which was largely prevented by immunization with
      fpIBD1. These results indicate that measurement of immunosuppression could be a
      useful strategy for assessing the efficacy of vaccines to protect against the
      consequences of IBDV infection.

PMID- 14676011
TI  - Growth enhancement in broiler chickens receiving CHEMEQRTM polymeric
      antimicrobial.
AB  - This study investigated the use of CHEMEQRTM polymeric antimicrobial as a means
      of enhancing health and growth rates in broiler chickens. One-day-old Cobb-500
      broilers were reared to 42 days. In trial 1, 100 birds received CHEMEQRTM
      polymeric antimicrobial via water, and 100 birds were untreated. Treated birds
      had significantly greater (P<0.0001) average daily gain (ADG), significantly
      lower (P<0.0016) feed conversion ratios, significantly lower (P<0.05) mortality,
      and a significantly lower (P<0.0042) viscosity of their ileal contents. In trial
      2, three groups of 40 birds received reducing dosages of CHEMEQRTM polymeric
      antimicrobial, and a fourth group remained untreated. Groups receiving CHEMEQRTM
      polymeric antimicrobial had significantly greater (P<0.05) ADG, and two groups
      had significantly lower (P<0.05) feed conversion ratios than the controls. In
      trial 3, groups of 40 birds received either CHEMEQRTM polymeric antimicrobial,
      Salinomycin or Lasalocid in-feed, or were untreated. Birds receiving CHEMEQRTM
      polymeric antimicrobial had significantly greater (P<0.05) ADG than those
      receiving Salinomycin. CHEMEQRTM polymeric antimicrobial helped to maintain the
      health and to improve the growth performance of broiler chickens.

PMID- 14676012
TI  - Rhabdomyosarcoma in a racing pigeon (Columba livia).
AB  - An adult racing pigeon (Columba livia) was presented with a subcutaneous mass on
      the ventral aspect of the right wing. A fine-needle aspirate and radiographic
      study of the mass were suggestive of highly invasive sarcomatous neoplasm.
      Euthanasia was decided because of the poor prognosis. Necropsy confirmed the
      highly invasive nature of the neoplasm, which also occupied a large portion of
      the right breast. There also was extensive osteolysis of the sternum with
      neoplastic invasion of the left breast and the coelomic cavity. Histopathology
      revealed a highly cellular, poorly demarcated, unencapsulated invasive sarcoma.
      Immunohistochemistry was positive for muscle actin, and myoglobin, weakly
      positive for vimentin, and negative for desmin, neuron-specific enolase and S-100
      protein, suggesting a diagnosis of undifferentiated rhabdomyosarcoma.

PMID- 14676013
TI  - In ovo infection with an avian leukosis virus causing fowl glioma: viral
      distribution and pathogenesis.
AB  - We have previously isolated an avian leukosis virus (ALV) from a chicken affected
      with so-called fowl glioma. A resistance-inducing factor test indicated that the
      isolate was classified into a subgroup A. The distribution and pathogenicity were
      investigated in C/O specific pathogen free chickens infected in ovo with this
      virus. Histologically, 11 of 12 (92%) infected birds had non-suppurative
      encephalitis and three birds (25%) showed the characteristic nodules of fowl
      glioma at 50 or 100 days of age. Non-suppurative myocarditis with matrix
      inclusions and atypical myocytes were also noted in nine (75%) of the birds and
      the ALV antigens were immunohistochemically detected in various general organs as
      well as the central nervous system and heart. The semi-quantitative determination
      of the proviral DNA and viral RNA supported the immunohistochemical results and
      indicated that the virus was likely to replicate especially in myocardial fibres.
      The isolated ALV failed to induce other neoplastic lesions in this line of
      chickens within the experimental period of 100 days, despite the broad tissue
      tropism throughout the body. These results confirmed that this virus was able to
      induce glioma in embryo-inoculated chickens.

PMID- 14676014
TI  - Iron metabolism in mynah birds (Gracula religiosa) resembles human hereditary
      haemochromatosis.
AB  - Iron overload is a very frequent finding in several animal species and a genetic
      predisposition is suggested. In one of the most commonly reported species with
      susceptibility for iron overload (mynah bird), it was recently shown that the
      cause of this pathophysiology is high uptake and retention of dietary iron. Here
      we compare susceptible (mynahs) with non-susceptible avian species (chickens) by
      evaluating iron uptake at the intestinal absorptive cell level. Enterocytes from
      mynahs and chickens were isolated and uptake of Fe(II) and Fe(III) was studied in
      vitro. It was found that Fe(III) uptake is much lower than Fe(II) uptake for both
      species. Although liver iron, present only in hepatocytes, was at least 10-fold
      higher in mynahs than chickens, enterocyte Fe(II) uptake was considerably higher
      in mynahs. Fe(II) uptake showed saturation at the studied concentrations in both
      species. Kinetic studies revealed a three-fold increase in Vmax for mynahs.
      Calculated values for the uptake kinetics of the probable membrane transporter
      suggest that mynah bird enterocytes have a significantly higher limiting uptake
      rate, due to the possible increase in the number of transporters when compared
      with chicken enterocytes. The susceptibility of this species is due to intestinal
      iron uptake despite hepatic iron accumulation, implicating a 'mis-sensing' of
      body iron similarly to human hereditary haemochromatosis.

PMID- 14676015
TI  - Effects of Senna occidentalis on chick bursa of Fabricius.
AB  - Senna occidentalis (L) Link (formerly called Cassia occidentalis) is a toxic
      leguminous plant found ubiquitously as a contaminant of crops. All parts of the
      plant are toxic, but most of the S. occidentalis toxicity is found in the seeds.
      S. occidentalis has been shown to be toxic to several animal species, causing
      degenerative lesions mainly in muscles. This is the first report describing
      alterations in chick lymphoid organs caused by S. occidentalis seeds. The
      objectives of this study were to describe the effects of the treatment with seeds
      and its fraction external tegument (TE) on the development of chicks and their
      lymphoid organs bursa of Fabricius and spleen. Chicks that received a commercial
      ration with 1% TE had reduced body and lymphoid organ weights. The bursa of
      Fabricius presented reduction in the diameters of the follicles, and in the
      thickness of the cortical and medullary regions. The spleen presented depleted
      lymphoid tissue in the white pulp. These results indicate that the active
      principle of S. occidentalis is more concentrated on its TE fraction, and that it
      can cause weight loss as well as alterations in the lymphoid organs in chicks.
      The consequences of these alterations should be further investigated.

PMID- 14676016
TI  - Survival of intestinal spirochaete strains from chickens in the presence of
      disinfectants and in faeces held at different temperatures.
AB  - This study aimed to evaluate the efficacy of some commonly used disinfectants in
      inactivating the pathogenic avian intestinal spirochaetes Brachyspira intermedia
      and Brachyspira pilosicoli, and to examine spirochaete survival in chicken caecal
      faeces held at 4 degrees C, 25 degrees C or 37 degrees C. Six disinfectants were
      evaluated at their recommended working concentrations: alkaline salts, quaternary
      ammonium, iodine as an iodophor, chlorine from a chlorine-release agent,
      glutaraldehyde and hydrogen peroxide. All but alkaline salts inactivated two
      different concentrations of both spirochaete species in less than 1 min in the
      presence of organic matter. Both spirochaete species at three different cell
      concentrations survived in caecal faeces at 37 degrees C for between 2 and 17 h.
      B. intermedia tended to survive for longer than B. pilosicoli, but the maximum
      survival time for both species at 4 degrees C was only 72 to 84 h. Hence, avian
      intestinal spirochaetes are rapidly inactivated by several common disinfectants,
      and their survival time in chicken caecal faeces is much less than has been
      reported for porcine intestinal spirochaetes in porcine faeces. It should be
      relatively easy to break the cycle of infection between batches of laying birds
      by resting sheds for a few days, and by using disinfectants on any residual
      faecal matter.

PMID- 14676018
TI  - Pancreatitis in wild zinc-poisoned waterfowl.
AB  - Four waterfowl were collected in the Tri-State Mining District (Oklahoma, Kansas
      and Missouri, USA), an area known to be contaminated with lead, cadmium and zinc
      (Zn). They were part of a larger group of 20 waterfowl collected to determine the
      exposure of birds to metal contamination at the site. The four waterfowl (three
      Branta canadensis, one Anas platyrhynchos) had mild to severe degenerative
      abnormalities of the exocrine pancreas, as well as tissue (pancreas, liver)
      concentrations of Zn that were considered toxic. The mildest condition was
      characterized by generalized atrophy of exocrine cells that exhibited cytoplasmic
      vacuoles and a relative lack of zymogen. The most severe condition was
      characterized by acini with distended lumens and hyperplastic exocrine tissue
      that completely lacked zymogen; these acini were widely separated by immature
      fibrous tissue. Because the lesions were nearly identical to the lesions reported
      in chickens and captive waterfowl that had been poisoned with ingested Zn, and
      because the concentrations of Zn in the pancreas and liver of the four birds were
      consistent with the concentrations measured in Zn-poisoned birds, we concluded
      that these waterfowl were poisoned by Zn. This may be the first reported case of
      zinc poisoning in free-ranging wild birds poisoned by environmental Zn.

PMID- 14676017
TI  - Prophylactic action of lipoic acid on oxidative stress and growth performance in
      broilers at risk of developing ascites syndrome.
AB  - The objective of this study was to assess the effects of dietary supplementation
      with lipoic acid (LA) on broilers maintained at 2235 m above sea level with high
      risk to develop ascites syndrome (AS). A total of 2040 chicks were fed under
      commercial conditions with water and specific diets ad libitum during 7 weeks in
      two consecutive experiments. Mortality and indicators of performance and
      oxidative stress were compared weekly in broilers fed a basal diet plus 0, 10,
      20, or 40 parts/10(6) LA. The effects of LA at 40 parts/10(6) were also studied
      during the initial 3 weeks or the last 4 weeks of the production cycle. Diets
      supplemented with 40 parts/10(6) of LA during 7 weeks significantly improved feed
      conversion, decreased general mortality and mortality attributable to AS, and
      lowered thiobarbituric acid reactive substances and hydroxyl radicals in liver,
      and increased total glutathione pool. Smaller doses or shorter periods of
      exposure to LA were partially effective. In conclusion, LA under our experimental
      conditions has a prophylactic action in broilers with high risk to develop AS due
      to oxygen availability limitation.

PMID- 14676019
TI  - The clinical and economic efficacy of HAART: a shift from inpatient medical to
      outpatient pharmaceutical care for HIV/AIDS patients in Northeastern Italy.

PMID- 14676020
TI  - Popular opinion leaders and HIV prevention peer education: resolving discrepant
      findings, and implications for the development of effective community programmes.
AB  - A series of community-level trials undertaken in the United States over the past
      10 years established the effectiveness of an HIV prevention intervention that
      systematically identifies, recruits, trains, and engages the popular opinion
      leaders (POLs) of a population to serve as behaviour change endorsers. Recently,
      several investigators reported unsuccessful attempts to implement peer education
      programmes for men who have sex with men in the United Kingdom and raised
      questions about whether peer-based programmes are effective or feasible. However,
      POL is a theory-based and very specialized intervention, and the UK peer
      education programmes did not incorporate many of POL's core or essential
      elements. Consequently, they were not evaluations of POL. In this article, core
      elements of the popular opinion leader model are presented; interpretations are
      made of possible reasons for the discrepant findings of the UK peer education and
      US POL interventions; and practical issues for applied programme development are
      discussed.

PMID- 14676021
TI  - Popular opinion leaders in London: a response to Kelly.
AB  - Controlled trials conducted in the USA provide clear evidence that peer education
      can bring about a reduction in high risk sexual behaviour among gay men. HIV
      prevention interventions that systematically identified, recruited, trained and
      engaged popular opinion leaders (POLs) made a significant impact on sexual
      behaviour at a community level in small US towns. However, recent trials
      conducted in the UK have failed to replicate these findings. A POL intervention
      in London made no significant impact at a community level on the risk behaviours
      of gay men. Jeffrey Kelly, one of the authors of the US studies, has identified
      nine core elements central to the popular opinion leader model. In Kelly's view
      'the UK projects were not tests of the popular opinion leader model because they
      did not employ most of these POL core elements'. The absence of any significant
      impact of the UK programmes on sexual risk behaviour at a community level was
      not, therefore, surprising. In fact, the London POL project incorporated all the
      core elements into its design and succeeded in employing seven out of nine in its
      delivery. Attempts to employ all the core elements, however, were hampered by
      problems in recruiting popular opinion leaders as well as barriers to
      communication. Process evaluation revealed that it was these obstacles which
      limited diffusion. This in turn explained the absence of any impact of the London
      POL project on sexual risk behaviour at a community level. The obstacles to
      successful diffusion in London have provided a valuable opportunity for examining
      the processes that underlie the POL model. Our study raises the question as to
      whether social interventions shown to be effective in one setting, place or
      moment in time can be replicated in another.

PMID- 14676022
TI  - Good in parts: the Gay Men's Task Force in Glasgow--a response to Kelly.
AB  - We know that peer education, or the use of popular opinion leaders (POLs), works
      in terms of reducing reported risk behaviour for HIV infection amongst gay men.
      The work of Jeffrey Kelly and his colleagues provides some of the best scientific
      evidence in support of this approach. Influenced by this work, we undertook a
      peer education intervention amongst gay men in bars in Glasgow--the Gay Men's
      Task Force (GMTF)--but failed to demonstrate any reduction in sexual risk
      behaviour for HIV infection. In this paper we describe why we were unable to
      repeat in Scotland the success in small cities in the USA of the POL model. Our
      explanations include: failure to replicate the 'core elements' of POL; spatial
      and temporal differences between the original POL settings and the bars of
      Glasgow; and the currency of ideas such as 'peer education' beyond the protocols
      designed for their implementation. However, we also describe some of the
      successful features of the GMTF in Glasgow, and the continued value of peer
      education in contributing to reductions in sexual risk behaviour for HIV
      infection.

PMID- 14676023
TI  - Accurate and inaccurate HIV transmission beliefs, stigmatizing and HIV protection
      motivation in northern Thailand.
AB  - We assessed the relation between accurate beliefs about HIV transmission and
      inaccurate beliefs about HIV transmission and emotional reactions to people with
      AIDS (PWA) and AIDS risk groups, stigmatizing attitudes and motivation to protect
      from HIV. In Chiang Rai, northern Thailand, 219 respondents filled in a
      structured questionnaire assessing accurate and inaccurate HIV transmission
      beliefs, emotional reactions towards PWA and AIDS risk groups, stigmatizing
      attitudes and motivation to protect from HIV according to variables from
      Protection Motivation Theory. Complete accurate beliefs about documented modes of
      HIV transmission were present in 47% of the respondents, while 26% of the
      respondents held one or more inaccurate beliefs about HIV transmission.
      Incomplete beliefs about documented modes of transmission were significantly
      related to stigmatizing beliefs towards people with AIDS (PWA), to lower
      vulnerability of HIV infection and lower self-efficacy in protection. Those who
      held inaccurate beliefs about HIV transmission reported more fear towards PWA and
      homosexuals and more irritation towards PWA and commercial sex workers. Persons
      who held inaccurate beliefs about HIV transmission also reported more
      stigmatizing attitudes, perceived AIDS as less severe, perceived a lower
      vulnerability and were less motivated to use condoms. Results of this study
      suggest that inaccurate beliefs about HIV transmission are related to fear and
      stigmatizing and undermine HIV prevention behaviour.

PMID- 14676024
TI  - The quality of life of HIV-infected women is associated with psychiatric
      morbidity.
AB  - This study evaluated the effect of clinical, demographic and psychiatric factors
      on the health-related quality of life of 76 women with HIV infection seen in two
      HIV reference centres in Brazil. The generic questionnaire for evaluation of
      Health-Related Quality of Life (SF-36), the Hospital Anxiety and Depression Scale
      (HAD) and the Clinical Interview Schedule (CIS-R) were used. The statistical
      tests included the covariance analysis. The patients' mean age was 37.4 years;
      44.7% had less than 8 years of schooling. A total of 44.8% were asymptomatic,
      28.9% symptomatic non-AIDS and 26.3% had AIDS. Most (77.6%) used two or three
      kinds of antiretrovirals; 36.8 and 30.3% achieved scores for anxiety and
      depression, respectively (HAD); and 48.7% for conspicuous psychiatric morbidity
      (CIS-R). The sub-group of the non-AIDS symptoms (clinical stage B) showed the
      worst quality of life. The variables which better explained the scoring variation
      on both the mental and physical components of the SF-36 were related to mental
      health. The more mental symptoms present, the worse the health-related quality of
      life. We must rethink care strategies in the area of mental health which are
      directed toward HIV+ patients, by virtue of the levels of mental symptoms found
      and the request for care which the research revealed.

PMID- 14676025
TI  - Validity of the Household and Leisure Time Activities questionnaire (HLTA) in a
      multiethnic HIV-positive population.
AB  - As individuals with HIV/AIDS continue to have longer life expectancies, it is
      vital that other health outcomes, such as functional status, be considered. The
      purpose of this study was to explore the psychometric properties of a new
      functional status measure, the Household and Leisure Time Activities (HLTA)
      questionnaire, in a multiethnic low-income HIV/AIDS population. The HLTA is an 11
      item questionnaire consisting of two scales designed to assess an individual's
      ability to perform routine home activities (household functioning scale) and to
      participate in leisure time activities (leisure-time functioning scale). The HLTA
      was administered, in the form of self-report questionnaires, to 385 consecutive
      patients seen at a comprehensive HIV/AIDS care facility serving low-income
      residents of Houston, Texas. Various psychometric procedures were then performed
      to assess properties, including reliability, construct validity, and concurrent
      validity. Reliability, assessed by Cronbach's alpha, was good for both scales
      (0.92, household functioning; and 0.94, leisure-time functioning). Validity was
      supported by findings from the confirmatory factor analysis and findings from the
      concurrent validity analyses. Overall, the results indicated that the HLTA has
      satisfactory psychometric properties and is appropriate for use with
      multicultural low-income HIV/AIDS patients.

PMID- 14676026
TI  - The impact of psychiatric symptoms, drug use, and medication regimen on non
      adherence to HIV treatment.
AB  - Identifying which mental disorders, substance use, and regimen factors influence
      non-adherence is a critical step in developing patient-customized interventions.
      In this cross-sectional study, 120 adults with HIV taking antiviral therapy
      completed interviews and questionnaires on their medication regimen, adherence
      behaviours, mental distress, and substance use patterns. They provided access to
      medical records for measures of immune health. Demographic characteristics,
      regimen factors, mental health indicators, and substance use variables were
      evaluated as predictors of four dichotomous non-adherent behaviours: running out
      of medications, not always taking medications as directed, taking below 95% of
      protease inhibitor doses, or having notations of non-compliance in the medical
      record. Non-adherence was prevalent and was related to immune health. Recent
      crack cocaine use was a risk factor for both taking a low proportion of PI
      medication and charted non-compliance notations. Heroin use and screening
      positive for social phobia were risk factors for running out of medication.
      Screening positive for any anxiety disorder reduced the risk of failing to take
      medications as directed. Clinicians caring for patients with HIV should screen
      for non-adherence using multiple behavioural indicators, and assess and treat
      substance use and anxiety disorders to reduce the risk of non-adherence.

PMID- 14676027
TI  - Adherence to antiretroviral therapy in rural persons living with HIV disease in
      the United States.
AB  - The current study delineated patterns and predictors of adherence to
      antiretroviral therapy in 329 persons living with HIV disease in rural areas of
      12 US states. Participants provided self-report data on patterns of HIV
      medication adherence, reasons for missing medication doses, psychological
      symptomatology, life-stressor burden, social support, ways of coping, coping self
      efficacy, the quality of their relationship with their main physician, and
      barriers to health care and social services. Based on adherence data collected
      via retrospective, self-report assessment instruments, only 50% of participants
      adhered consistently to antiretroviral therapy regimens in the past week.
      Consistent adherence was more common in White participants, persons who had
      progressed to AIDS, and 'native infections' (i.e. persons who were born, raised,
      and infected in their current place of residence). Logistic regression analyses
      indicated that consistent adherence was reported by persons who drank less
      alcohol, had a good relationship with their main physician, and engaged in more
      active coping in response to HIV-related life stressors. As the number of rural
      persons living with HIV disease continues to increase, research that identifies
      correlates of non-adherence and conceptualizes approaches to optimize adherence
      in this group is urgently needed.

PMID- 14676028
TI  - Gender roles and HIV sexual risk vulnerability of Roma (Gypsies) men and women in
      Bulgaria and Hungary: an ethnographic study.
AB  - Roma, the largest ethnic minority group in Central and Eastern Europe, have
      cultures that are traditional, often closed, and autonomous of majority
      populations. Roma communities are characterized by pervasive social health
      problems, widespread poverty, limited educational opportunities, and
      discrimination. Although some evidence suggests high levels of HIV sexual risk
      behaviour among Roma, little is known about the cultural and social context in
      which risk behaviour occurs. In-depth interviews were used to elicit detailed
      information about types of sexual partnerships and sexual risk behaviour
      practices occurring in them, use and perception of protection, knowledge and
      beliefs about AIDS and STDs, and sexual communication patterns in a sample of 42
      men and women aged 18-52 living in Roma community settlements in Bulgaria and
      Hungary. Analysis of the interview data revealed that men have great sexual
      freedom before and during marriage, engage in a wide range of unprotected
      practices with primary and multiple outside partners, and have much more
      relationship power and control. In contrast, women are expected to maintain
      virginity before marriage and then sexual exclusivity to their husbands. Condom
      use is not normative and is mainly perceived as a form of contraception. Although
      awareness of AIDS was common, it was generally not perceived as a personal
      threat. Misconceptions about how HIV is transmitted are widespread, and women -
      in particular - had very little knowledge about STDs, HIV transmission, and
      protective steps. There is an urgent need for the development of HIV prevention
      programs culturally sensitive to Roma populations in Eastern Europe, where HIV
      rates are rapidly rising.

PMID- 14676029
TI  - Posttraumatic stress disorder symptoms, salivary cortisol, medication adherence,
      and CD4 levels in HIV-positive individuals.
AB  - Previous research has reported rates of posttraumatic stress disorder (PTSD)
      following diagnosis with a life-threatening disease ranging from 5 to 42%.
      However, few studies have examined the impact of PTSD symptoms on disease markers
      or adherence to medical regimens. The present study represents an initial
      examination of the relationships among self-reported PTSD symptoms stemming from
      diagnosis with HIV, CD4 cell counts, salivary cortisol levels and adherence to
      highly active antiretroviral therapy (HAART) in 110 African-American and
      Caucasian individuals with HIV. Results revealed that the relationship between
      PTSD and disease progression is multifaceted: PTSD symptoms were related to worse
      adherence to HAART therapy, but were also associated with lower morning salivary
      cortisol levels and higher CD4 cell counts.

PMID- 14676030
TI  - Generic biomass functions for Norway spruce in Central Europe--a meta-analysis
      approach toward prediction and uncertainty estimation.
AB  - To facilitate future carbon and nutrient inventories, we used mixed-effect linear
      models to develop new generic biomass functions for Norway spruce (Picea abies
      (L.) Karst.) in Central Europe. We present both the functions and their
      respective variance-covariance matrices and illustrate their application for
      biomass prediction and uncertainty estimation for Norway spruce trees ranging
      widely in size, age, competitive status and site. We collected biomass data for
      688 trees sampled in 102 stands by 19 authors. The total number of trees in the
      "base" model data sets containing the predictor variables diameter at breast
      height (D), height (H), age (A), site index (SI) and site elevation (HSL) varied
      according to compartment (roots: n = 114, stem: n = 235, dry branches: n = 207,
      live branches: n = 429 and needles: n = 551). "Core" data sets with about 40%
      fewer trees could be extracted containing the additional predictor variables
      crown length and social class. A set of 43 candidate models representing
      combinations of lnD, lnH, lnA, SI and HSL, including second-order polynomials and
      interactions, was established. The categorical variable "author" subsuming mainly
      methodological differences was included as a random effect in a mixed linear
      model. The Akaike Information Criterion was used for model selection. The best
      models for stem, root and branch biomass contained only combinations of D, H and
      A as predictors. More complex models that included site-related variables
      resulted for needle biomass. Adding crown length as a predictor for needles,
      branches and roots reduced both the bias and the confidence interval of
      predictions substantially. Applying the best models to a test data set of 17
      stands ranging in age from 16 to 172 years produced realistic allocation patterns
      at the tree and stand levels. The 95% confidence intervals (% of mean prediction)
      were highest for crown compartments (approximately +/- 12%) and lowest for stem
      biomass (approximately +/- 5%), and within each compartment, they were highest
      for the youngest and oldest stands, respectively.

PMID- 14676031
TI  - Petiole length and biomass investment in support modify light interception
      efficiency in dense poplar plantations.
AB  - Leaf architecture, stand leaf area index and canopy light interception were
      studied in 13 poplar clones growing in a second rotation of a coppice plantation,
      to determine the role of leaf architectural attributes on canopy light-harvesting
      efficiency and to assess biomass investment in leaf support tissue. Stand leaf
      area index (L) varied from 2.89 to 6.99, but L was only weakly associated with
      canopy transmittance (TC). The weak relationship between TC and L was a result of
      a higher degree of foliage aggregation at larger values of L, leading to lower
      light-interception efficiency in stands with greater total leaf area. We observed
      a strong increase in leaf aggregation and a decrease in light-harvesting
      efficiency with decreasing mean leaf petiole length (PL) but not with leaf size,
      possibly because, in cordate or deltoid poplar leaves, most of the leaf area is
      located close to the petiole attachment to the lamina. Although PL was the key
      leaf characteristic of light-harvesting efficiency, clones with longer petioles
      had larger biomass investments in petioles, and there was a negative relationship
      between PL and L, demonstrating that enhanced light harvesting may lead to an
      overall decline in photosynthesizing leaf surface. Upper-canopy leaves were
      generally larger and had greater dry mass (MA) and nitrogen per unit area (NA)
      than lower-canopy leaves. Canopy plasticity in MA and NA was higher in clones
      with higher foliar biomass investment in midrib, and lower in clones with
      relatively longer petioles. These relationships suggest that there is a trade-off
      between photosynthetic plasticity and biomass investment in support, and also
      that high light-harvesting efficiency may be associated with lower photosynthetic
      plasticity. Our results demonstrate important clonal differences in leaf
      aggregation that are linked to leaf structure and biomass allocation patterns
      within the leaf.

PMID- 14676032
TI  - Relative importance of photosynthetic physiology and biomass allocation for tree
      seedling growth across a broad light gradient.
AB  - Studies of tree seedling physiology and growth under field conditions provide
      information on the mechanisms underlying inter- and intraspecific differences in
      growth and survival at a critical period during forest regeneration. I compared
      photosynthetic physiology, growth and biomass allocation in seedlings of three
      shade-tolerant tree species, Virola koschynii Warb., Dipteryx panamensis
      (Pittier) Record & Mell and Brosimum alicastrum Swartz., growing across a light
      gradient created by a forest-pasture edge (0.5 to 67% diffuse transmittance
      (%T)). Most growth and physiological traits showed nonlinear responses to light
      availability, with the greatest changes occurring between 0.5 and 20 %T. Specific
      leaf area (SLA) and nitrogen per unit leaf mass (N mass) decreased, maximum
      assimilation per unit leaf area (A area) and area-based leaf N concentration (N
      area) increased, and maximum assimilation per unit leaf mass (A mass) did not
      change with increasing irradiance. Plastic responses in SLA were important
      determinants of leaf N and A area across the gradient. Species differed in
      magnitude and plasticity of growth; B. alicastrum had the lowest relative growth
      rates (RGR) and low plasticity. Its final biomass varied only 10-fold across the
      light gradient. In contrast, the final biomass of D. panamensis and V. koschynii
      varied by 100- and 50-fold, respectively, and both had higher RGR than B.
      alicastrum. As light availability increased, all species decreased biomass
      allocation to leaf tissue (mass and area) and showed a trade-off between
      allocation to leaf area at a given plant mass (LAR) and net gain in mass per unit
      leaf area (net assimilation rate, NAR). This trade-off largely reflected declines
      in SLA with increasing light. Finally, A area was correlated with NAR and both
      were major determinants of intraspecific variation in RGR. These data indicate
      the importance of plasticity in photosynthetic physiology and allocation for
      variation in tree seedling growth among habitats that vary in light availability.

PMID- 14676033
TI  - Xylem sap flow and drought stress of Fraxinus excelsior saplings.
AB  - We report on diurnal and seasonal variations in sap flow rate and stem water
      potential of Fraxinus excelsior L. saplings growing at the edge of a Fraxino
      Aceretum forest in western Germany. Because of shallow soil, the trees were
      subjected to drought in summer. When soil water availability was not limiting,
      sap flow rate was related to changes in solar radiation and vapor pressure
      deficit. Maximum transpiration rates per leaf area were 3.5-7.4 mmol m-2 s-1, and
      maximum daily totals were 1.7-3.3 kg m-2 day-1. Under drought conditions, stem
      water potential dropped to midday minima of -2.6 to -3.5 MPa and sap flow rate
      was strongly related to this parameter. After the drought period, reduced
      apparent (whole-plant) hydraulic conductance was observed, which was attributed
      to a continued reduction in stomatal conductance after the drought stress had
      ceased. A model was developed that linked sap flow rate directly to climatic
      variables and stem water potential. Good correlation between measured and
      simulated sap flow rates allowed the model to be used for data interpretation.

PMID- 14676034
TI  - Responses to ultraviolet-B radiation by purely symbiotic and NO3-fed nodulated
      tree and shrub legumes indigenous to southern Africa.
AB  - Purely symbiotic and NO3-fed nodulated seedlings of Virgilia oroboides (Bergius)
      T.M. Salter, Cyclopia maculata (L.) Vent and Podalyria calyptrata Willd. were
      exposed to biologically effective ultraviolet-B radiation (UV-B) to assess the
      effects of above- and below-ambient UV-B on growth, symbiotic function and
      metabolite concentrations. Seedlings were grown outdoors either on tables under
      ambient or 34 or 66% above-ambient UV-B conditions (UV-B100 control, UV-B134 and
      UV-B166, respectively), or in chambers providing below-ambient (22% of ambient)
      UV-B (UV-B22) along with a UV-A control and a photosynthetically active radiation
      (PAR) control. Exposure of seedlings to UV-B166 radiation reduced (P < or = 0.05)
      leaf and stem dry mass by 34 and 39%, respectively, in C. maculata, and reduced
      leaf nitrogen concentration (%N) by 12% in V. oroboides. Nodule %N in C. maculata
      and stem %N in P. calyptrata also decreased (P < or = 0.05) in response to UV-B22
      radiation compared with the UV-A control, but not compared with the PAR control.
      Concentrations of flavonoids, soluble sugars and starch were unaltered by the UV
      B treatments. Application of 1 mM NO3 to UV-B166-treated seedlings increased
      whole-plant dry mass of V. oroboides and P. calyptrata by 47 and 52%,
      respectively. Dry mass of organs, nodule %N and total N concentration of these
      species also increased with NO3 application. However, NO3 supply decreased (P <
      or = 0.05) nodule dry mass, stem %N and leaf %N as well as root and leaf
      anthocyanin concentrations in C. maculata. In terms of UV-B x N interactions, dry
      mass of stems, roots, nodules and total biomass of NO3-fed C. maculata seedlings
      were reduced, and nodule %N, total N and leaf anthocyanins were depressed by the
      UV-B134 and UV-B166 treatments relative to UV-B100-treated seedlings. Although we
      found that above-ambient UV-B had no effects on growth and symbiotic function of
      V. oroboides and P. calyptrata seedlings, feeding NO3 to these species increased
      (P < or = 0.05) seedling growth. In contrast, purely symbiotic C. maculata
      seedlings were sensitive to the UV-B166 radiation treatment, and adding NO3
      further increased their sensitivity to both the UV-B134 and UV-B166 treatments.

PMID- 14676035
TI  - Use of modeled photosynthesis and decomposition to describe tree growth at the
      northern tree line.
AB  - Growth of subarctic Scots pine (Pinus sylvestris L.) trees was investigated by a
      combination of process-based models and dendroecological approaches. Tree ring
      width indices were strongly autocorrelated and correlated with simulated
      photosynthetic production of the previous year and with organic matter N
      mineralization of the current year. An autoregressive model, with photosynthesis
      and N mineralization as external inputs, explained growth of the trees well.
      However, relationships for the period 1950-1992 differed significantly from
      relationships for the period 1876-1949; the slope of the regression of tree ring
      width index and photosynthesis was lower for the 1950-1992 period. Also, the
      autocorrelation structure of the data changed. First-order autocorrelation
      decreased and second-order autocorrelation increased from the earlier to the
      later period. This means that growth is becoming less sensitive to variations in
      photosynthetic production, whereas the relationships between growth and N
      mineralization are remaining fairly constant. We postulate that, although
      photosynthesis has increased in response to increasing CO2 concentrations, tree
      growth rate cannot parallel the increase in photosynthesis because potential
      growth rate is limited directly by temperature.

PMID- 14676036
TI  - Spatial and temporal variations in leaf area index, specific leaf area and leaf
      nitrogen of two co-occurring savanna tree species.
AB  - Foliage growth, mass- and area-based leaf nitrogen concentrations (Nm and N a)
      and specific leaf area (SLA) were surveyed during a complete vegetation cycle for
      two co-occurring savanna tree species: Crossopteryx febrifuga (Afzel. ex G. Don)
      Benth. and Cussonia arborea A. Rich. The study was conducted in the natural
      reserve of Lamto, Ivory Coast, on isolated and clumped trees. Leaf flush occurred
      before the beginning of the rainy season. Maximum leaf area index (LAI), computed
      on a projected canopy basis for individual trees, was similar (mean of about 4)
      for both species. Seasonal courses of the ratio of actual to maximum LAI were
      similar for individuals of the same species, but differed between species. For C.
      febrifuga, clumped trees reached their maximum LAI before isolated trees. The LAI
      of C. arborea trees did not differ between clumped and isolated individuals, but
      maximum LAI was reached about 2 months later than for C. febrifuga. Leaf fall was
      associated with decreasing soil water content for C. arborea. For C. febrifuga,
      leaf fall started before the end of the rainy period and was independent of
      changes in soil water content. These features lead to a partial niche separation
      in time for light resource acquisition between the two species. Although Nm, N a
      and SLA decreased with time, SLA and N a decreased later in the vegetation cycle
      for C. arborea than for C. febrifuga. For both species, N a decreased and SLA
      increased with decreasing leaf irradiance within the canopy, although effects of
      light on leaf characteristics did not differ between isolated and clumped trees.
      Given relationships between N a and photosynthetic capacities previously reported
      for these species, our results show that C. arborea exhibits higher
      photosynthetic capacity than C. febrifuga during most of the vegetation cycle and
      at all irradiances.

PMID- 14676037
TI  - Phytohormones and shoot growth in a three-generation hybrid poplar family.
AB  - Hybrid vigor for secondary growth in poplar has been linked with increased
      gibberellin (GA) concentration in cambial tissue, but the relationship between
      concentrations of GAs and hybrid vigor of primary growth has not been
      investigated. We explored associations between concentrations of GAs, abscisic
      acid (ABA) and indoleacetic acid (IAA) and shoot extension in a hybrid family of
      Populus deltoides Bartr. ex Marsh. (Clone ILL-129) and P. trichocarpa Torr. &
      Gray (Clone 93-968) and two F1 and 67 F2 genotypes. Rapidly elongating subapical
      internodes from shoots of 4-year-old clonal saplings were selected for hormone
      analysis. The F1 hybrids displayed heterosis (hybrid vigor) for primary growth as
      a result of the complementation of dominance for increased internode length from
      the P. trichocarpa parent and dominance for increased diameter from the P.
      deltoides parent. Internodes from the faster-elongating shoots of the P.
      trichocarpa parent had a fourfold higher concentration of bioactive GA1 and
      higher concentrations of GA20, GA44, GA29 and GA8 than the P. deltoides parent.
      However, the two fast-growing F1 hybrids had low concentrations of all five GAs,
      with concentrations similar to those of the slower-elongating P. deltoides
      parent. Concentrations of ABA and IAA were correlated with GA concentrations and
      there was thus no evidence of a consistent promoting or inhibiting effect of ABA
      or IAA within the F1 family. These results indicate that heterosis for internode
      growth was not primarily regulated by hormone concentration. The segregating
      population of F2 hybrids was analyzed to assess the possible utility of hormone
      screening as a selection tool. The internodes of most of the F2 hybrids were
      smaller than those of their F1 parents and the larger P. trichocarpa parent.
      Among the F2 hybrids, mature internode length varied fourfold, and was correlated
      with lengths of young, subapical internodes from which hormones were analyzed. In
      these internodes, GA1 concentrations were negatively correlated with length (r =
      0.41), diameter (0.33) and mass (0.50). Indoleacetic acid concentration was
      negatively correlated only with diameter (r = 0.37) and positively correlated
      with GA1 (r = 0.46), whereas ABA concentration was not correlated with any
      parameter. Thus, in the F2 population, variation in hormone concentration was not
      primarily responsible for the variation in shoot growth, indicating that
      selection for individuals with high GA concentration may not be an effective
      strategy for identifying vigorous hybrid genotypes.

PMID- 14676038
TI  - The dwarfing mechanism of citrus rootstocks F&A 418 and #23 is related to
      competition between vegetative and reproductive growth.
AB  - The annual development of Navelina (Citrus sinensis (L.) Osbeck) trees budded on
      three hybrid citrus rootstocks was studied. Two rootstocks, named #23 and #24,
      were obtained from the cross of Troyer citrange (C. sinensis x Poncirus
      trifoliata (L.) Raf.) x Cleopatra mandarin (C. reshni Hort. ex Tan.). The third
      rootstock, named F&A 418, came from a cross of Troyer citrange x common mandarin
      (C. deliciosa Ten.). Rootstocks #23 and F&A 418 are dwarfing rootstocks and
      reduce the size of the scion by about 75%. Rootstock #24 yields a standard size
      scion. Major growth differences that influenced tree size were apparent during
      the first summer after grafting and appeared to be related to fruit productivity,
      because defruiting the dwarfed scions caused a significant increase in vegetative
      shoot development, including summer sprouting. The reduced growth of the dwarfed
      scions was not restored by hormone application, indicating that a hormonal
      deficiency is unlikely to be the primary reason for scion dwarfing, although
      differences in gibberellin concentrations were found in actively growing shoots.
      Leaf photosynthesis was similar in scions on all three rootstocks, but the
      carbohydrate accumulation in fruits and fibrous roots during the summer sprouting
      period was significantly greater in the dwarfed trees than in the standard trees.
      Our results suggest that the dwarfing mechanism induced by the F&A 418 and #23
      rootstocks is mediated by enhanced reproductive development and fruit growth,
      resulting in reduced vegetative development in the summer. Thus, a change in the
      pattern of assimilate distribution appears to be one of the main components of
      the dwarfing mechanism.

PMID- 14676039
TI  - Sclerophylly and leaf anatomical traits of five field-grown olive cultivars
      growing under drought conditions.
AB  - Leaf-level morphological and structural adaptations to reduce water loss were
      examined in five olive (Olea europaea L.) tree cultivars (Arbequina, Blanqueta,
      Cobrancosa, Manzanilla and Negrinha) growing under field conditions with low
      water availability. Leaf measurements included leaf tissue thickness, stomatal
      density, leaf area, leaf mass per unit area, density of leaf tissue, relative
      water content, succulence, water saturation deficit, water content at saturation
      and cuticular transpiration rate. We found considerable genotypic differences
      among the cultivars. Negrinha, Manzanilla and Cobrancosa had more morphological
      and structural leaf adaptations to protect against water loss than the other
      cultivars. Manzanilla and Negrinha enhanced their sclerophylly by building
      parenchyma tissues and increasing protective structures like the upper cuticle
      and both the upper and lower epidermis. Cobrancosa exhibited good protection
      against water loss through high density of foliar tissue and by thick cuticle and
      trichome layers. Compared with the Negrinha, Manzanilla and Cobrancosa cultivars,
      Arbequina leaves had a thinner trichome layer, implying that the leaves were less
      protected against water loss; however, the development of smaller leaves may
      reduce water loss at the whole-plant level. Among cultivars, Blanqueta had the
      largest leaves and some anatomical traits that may lead to high water loss,
      especially from the adaxial surface. The mechanisms employed by the cultivars to
      cope with summer stress are discussed at the morpho-structural level.

PMID- 14676040
TI  - Metal chelation therapy for Alzheimer disease.

PMID- 14676041
TI  - Treatments of Parkinson disease: circa 2003.
AB  - Parkinson disease (PD) is a progressive degenerative neurological disorder
      characterized by resting tremor, bradykinesia, cogwheel rigidity, and postural
      instability.1 In the later stages, approximately 25% or more of patients develop
      cognitive compromise. The cardinal pathological features of PD are degeneration
      of dopaminergic neurons in the substantia nigra pars compacta and their axons,
      which project principally to the caudate and putamen, and the presence of
      eosinophilic intracytoplasmic inclusions, Lewy bodies.2-3 Although the loss of
      neurons is most conspicuous in the substantia nigra pars compacta, neuronal loss
      and/or Lewy bodies are found in other brain regions (eg, the locus coeruleus,
      entorhinal region, and amygdala),2 which suggests that treatments that target
      only the nigrostriatal dopaminergic system, though they may substantially benefit
      patients, are unlikely to completely resolve the deficits of PD.

PMID- 14676042
TI  - Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta
      amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical
      trial.
AB  - BACKGROUND: Alzheimer disease (AD) may be caused by the toxic accumulation of
      beta-amyloid (Abeta). OBJECTIVE: To test this theory, we developed a clinical
      intervention using clioquinol, a metal-protein-attenuating compound (MPAC) that
      inhibits zinc and copper ions from binding to Abeta, thereby promoting Abeta
      dissolution and diminishing its toxic properties. METHODS: A pilot phase 2
      clinical trial in patients with moderately severe Alzheimer disease. RESULTS:
      Thirty-six subjects were randomized. The effect of treatment was significant in
      the more severely affected group (baseline cognitive subscale score of the
      Alzheimer's Disease Assessment Scale, >/=25), due to a substantial worsening of
      scores in those taking placebo compared with minimal deterioration for the
      clioquinol group. Plasma Abeta42 levels declined in the clioquinol group and
      increased in the placebo group. Plasma zinc levels rose in the clioquinol-treated
      group. The drug was well tolerated. CONCLUSION: Subject to the usual caveats
      inherent in studies with small sample size, this pilot phase 2 study supports
      further investigation of this novel treatment strategy using a metal-protein
      attenuating compound.

PMID- 14676043
TI  - Cerebrospinal fluid tau and beta-amyloid: how well do these biomarkers reflect
      autopsy-confirmed dementia diagnoses?
AB  - BACKGROUND: Tau and beta-amyloid (Abeta) are proposed diagnostic biomarkers for
      Alzheimer disease (AD). Previous studies report their relationship to clinical
      diagnoses of AD and other dementias. To understand their value as predictors of
      disease-specific pathology, levels determined during life must be correlated with
      definitive diagnoses in mixed dementia groups and cognitively normal subjects.
      OBJECTIVES: To correlate antemortem cerebrospinal fluid (CSF) tau and Abeta
      levels with definitive dementia diagnosis in a diverse group of patients; to
      calculate statistics for CSF tau and Abeta. DESIGN: Prospective study. SETTING:
      Ten clinics experienced in the diagnosis of neurodegenerative dementias. Patients
      One hundred six patients with dementia and 4 cognitively normal subjects with a
      definitive diagnosis, and 69 clinically diagnosed cognitively normal subjects.
      MAIN OUTCOME MEASURES: Correlation of CSF tau and Abeta with final diagnosis.
      RESULTS: Mean tau level was 612 pg/mL for the 74 patients with AD, 272 pg/mL for
      10 patients with frontal dementia, 282 pg/mL for 3 patients with dementia with
      Lewy bodies, and 140 pg/mL for 73 cognitively normal control subjects. Tau was
      less than 334 pg/mL for 20 patients with AD. Abeta42 was reduced in patients with
      AD (61 fmol/mL) compared with patients with frontal dementia (133 fmol/mL) and
      control subjects (109 fmol/mL), but not compared with patients with dementia with
      Lewy bodies (14 fmol/mL) or prion disease (60 fmol/mL). CONCLUSIONS: Elevated CSF
      tau levels are associated with AD pathology and can help discriminate AD from
      other dementing disorders. However, some patients with AD have a level less than
      the mean +/- 2 SDs of the cognitively normal cohort.

PMID- 14676044
TI  - Stroke and the risk of Alzheimer disease.
AB  - BACKGROUND: Alzheimer disease (AD) and stroke are common in elderly individuals,
      but the relation between these 2 disorders remains uncertain. OBJECTIVE: To
      investigate the association between a clinical history of stroke and subsequent
      risk of AD. DESIGN: A cohort of 1766 Medicare recipients without dementia
      participated in a longitudinal follow-up study from 1992 through 1999 in upper
      Manhattan, New York, NY. History of stroke and presence of cardiovascular risk
      factors were ascertained at the onset of the study. Incidence rates for AD among
      those with and without stroke were calculated; proportional hazards ratios were
      computed using age at onset of the disease as the time-to-event variable.
      RESULTS: The annual incidence for AD was 5.2% among individuals with stroke vs 4%
      for those without stroke. The hazards ratio for AD among those with a history of
      stroke was 1.6 (95% confidence interval, 1.0-2.4) compared with those without
      stroke. Of the vascular risk factors, hypertension, diabetes, and heart disease,
      only diabetes related to risk of AD in the absence of stroke. Stroke remained
      weakly associated with AD in the absence of these factors, but risk significantly
      increased with the additional factors of hypertension (relative risk, 2.3; 95%
      confidence interval, 1.4-3.6), diabetes (relative risk, 4.6; 95% confidence
      interval, 2.2-9.5), or heart disease (relative risk, 2.0; 95% confidence
      interval, 1.2-3.2). CONCLUSIONS: Stroke is associated with AD among elderly
      individuals. The relation is strongest in the presence of known vascular risk
      factors. The observed association between stroke and AD might relate to an
      underlying systemic vascular disease process, or alternatively, to the additive
      effects of stroke and AD pathologic features, leading to an earlier age at onset
      of disease.

PMID- 14676045
TI  - Misdiagnosis of spontaneous intracranial hypotension.
AB  - BACKGROUND: Spontaneous intracranial hypotension is an important cause of "new
      daily persistent headaches" but is not a well-recognized entity. The misdiagnosis
      of spontaneous intracranial hypotension can have serious consequences. METHODS:
      The clinical course in 18 consecutive patients with spontaneous intracranial
      hypotension who were evaluated for definitive surgical treatment of the
      underlying spontaneous spinal cerebrospinal fluid leak from January 1, 2001,
      through June 30, 2002, was investigated by correspondence with the patients and
      physicians. RESULTS: Seventeen patients (94%) initially received an incorrect
      diagnosis, and the diagnostic delay ranged from 4 days to 13 years (median, 5
      weeks; mean, 13 months). Migraine, meningitis, and psychogenic disorder were the
      most commonly entertained diagnoses. Diagnostic or therapeutic procedures for
      disorders that mimicked spontaneous intracranial hypotension included cerebral
      arteriography in 2 patients, craniotomies for Chiari malformation in 2 patients,
      craniotomy for evacuation of subdural hematomas in 1 patient, and brain biopsy in
      1 patient. CONCLUSIONS: Patients with spontaneous intracranial hypotension are
      commonly misdiagnosed, causing a significant delay in the initiation of effective
      treatments and exposing patients to the risks associated with treatment for
      disorders that mimic intracranial hypotension. Increasing the awareness of this
      spontaneous type of intracranial hypotension is required to decrease the high
      rate of misdiagnosis.

PMID- 14676046
TI  - A controlled trial of rotigotine monotherapy in early Parkinson's disease.
AB  - BACKGROUND: Oral dopamine agonists are effective for treating early Parkinson's
      disease (PD). Rotigotine is a dopamine agonist delivered through a silicone-based
      transdermal patch that is replaced every 24 hours. OBJECTIVES: To assess the
      efficacy and safety of rotigotine in patients with PD not receiving dopaminergic
      medications. DESIGN: Randomized, double-blind, placebo-controlled study. Patients
      Two hundred forty-two patients with early PD. Intervention Treatment with patches
      containing either 4.5, 9.0, 13.5, or 18.0 mg of rotigotine or placebo for 11
      weeks. Main Outcome Measure The change in the sum of the scores of the activities
      of daily living and motor components of the Unified Parkinson's Disease Rating
      Scale from baseline to the end of treatment. RESULTS: There was a significant
      dose-related improvement in the motor and activities of daily living Unified
      Parkinson's Disease Rating Scale score between baseline and week 11 for the 13.5-
      and 18.0-mg groups compared with placebo (placebo, 0.3 +/- 7.7; 13.5-mg group,
      5.1 +/- 7.0, P =.001; 18.0-mg group, 5.3 +/- 7.0, P<.001). Adverse experiences
      that occurred more commonly among subjects randomized to active treatment vs
      placebo included nausea, application site reactions, dizziness, insomnia,
      somnolence, vomiting, and fatigue. CONCLUSIONS: Rotigotine can be safely
      administered once daily transdermally and improves parkinsonian signs in patients
      with early PD.

PMID- 14676047
TI  - Association of ischemic lesion patterns on early diffusion-weighted imaging with
      TOAST stroke subtypes.
AB  - BACKGROUND: Different topographic patterns in patients who experience an acute
      ischemic stroke may be related to specific stroke causes. OBJECTIVE: To determine
      if lesion patterns on early diffusion-weighted imaging (DWI) are associated with
      stroke subtypes determined by the TOAST (Trial of ORG 10172 in Acute Stroke
      Treatment) classification. DESIGN: Cross-sectional study. SETTING: General
      community hospital. Patients We studied 172 consecutive ischemic stroke patients
      with a symptomatic lesion on DWI performed within 24 hours of stroke onset. MAIN
      OUTCOME MEASURES: Lesion patterns on DWI were classified into single lesions
      (corticosubcortical, cortical, subcortical > or =15 mm, or subcortical <15 mm),
      scattered lesions in one vascular territory (small scattered lesions or confluent
      with additional lesions), and multiple lesions in multiple vascular territories
      (in the unilateral anterior circulation, in the posterior circulation, in
      bilateral anterior circulations, or in anterior and posterior circulations).
      RESULTS: We found an overall significant relationship between DWI lesion patterns
      and TOAST stroke subtypes (P<.001). Corticosubcortical single lesions (P =.01),
      multiple lesions in anterior and posterior circulations (P =.03), and multiple
      lesions in multiple cerebral circulations (P =.008) were associated with
      cardioembolism. Multiple lesions in the unilateral anterior circulation (P =.04)
      and small scattered lesions in one vascular territory (P =.06) were related to
      large-artery atherosclerosis. Nearly half (11/23) of the patients with a single
      subcortical lesion that was 15 mm or larger were classified as having cryptogenic
      strokes (P =.001), although 9 of these patients had a classic lacunar syndrome
      without cortical hypoperfusion. CONCLUSIONS: Early DWI lesion patterns are
      associated with specific stroke causes. Conventional 15-mm criteria for lacunes,
      however, may underestimate the diagnosis of small-vessel occlusion with DWI.

PMID- 14676048
TI  - Atrophy is detectable within a 3-month period in untreated patients with active
      relapsing remitting multiple sclerosis.
AB  - BACKGROUND: Atrophy is recognized as a measure of destructive changes in multiple
      sclerosis (MS). The time course and pathologic mechanisms of atrophy development
      are not well understood. Significant atrophy was reported to occur within 9 to 12
      months in relapsing remitting MS. OBJECTIVES: To test whether atrophy can be
      detected over short time intervals, and to evaluate its relationship to
      inflammation. DESIGN AND METHODS: Prior to randomization to a treatment trial,
      138 untreated patients with relapsing remitting MS had 3 magnetic resonance
      imaging scans within a mean +/- SD follow-up of 76 +/- 20.2 days. Brain
      parenchymal fraction (BPF), a normalized measure of whole brain volume, the
      proportion of active (gadolinium-enhancing) scans, and the volume of T1-weighted
      gadolinium-enhancing and T2-weighted hyperintense lesions were determined at all
      time points. An annualized atrophy rate was estimated by calculating a regression
      slope. RESULTS: The median Expanded Disability Status Scale score was 3.5, the
      mean disease duration was 7.6, and the mean age was 38.5 years. The BPF decreased
      significantly by -0.229% from scan 1 to scan 3, while the proportion of active
      scans remained high (65%, 63%, and 67%). The BPF change was only weakly
      correlated to the volume of T1-weighted gadolinium-enhancing lesions in scan 1 (r
      = -0.185). The estimated annualized atrophy rate was -1.06% (95% confidence
      interval, -1.50% to -0.62%). CONCLUSIONS: The annualized atrophy rate found in
      this study is comparable with rates reported previously. Measurements of BPF
      allow detection of atrophy over short time intervals in active disease. The short
      term relationship of inflammation to atrophy development was weak. Brain
      parenchymal fraction might be a promising measure in future phase 2 studies of
      agents, with an expected effect on tissue-destructive pathologic mechanisms of
      MS.

PMID- 14676049
TI  - Platelet amyloid precursor protein abnormalities in mild cognitive impairment
      predict conversion to dementia of Alzheimer type: a 2-year follow-up study.
AB  - BACKGROUND: Alteration of the amyloid precursor protein (APP) forms ratio has
      been described in the platelets of patients with dementia of Alzheimer type (DAT)
      and in a subset of subjects with mild cognitive impairment (MCI). OBJECTIVE: To
      evaluate the potential role of the platelet APP forms ratio in predicting
      progression from MCI to DAT. DESIGN: Thirty subjects with MCI underwent a
      clinical and neuropsychological examination and a determination of the platelet
      APP forms ratio. Subjects were followed up periodically for 2 years, and the
      progression to dementia was evaluated. SETTING: Community population-based sample
      of patients admitted for memory complaints. RESULTS: Patients who progressed to
      DAT at the 2-year follow-up (n = 12) showed a significant decrease of baseline
      platelet APP forms ratio values (mean +/- SD, 0.36 +/- 0.28) compared with stable
      MCI subjects (mean +/- SD, 0.73 +/- 0.32) (P<.01) and patients who developed
      other types of dementia (mean +/- SD, 0.83 +/- 0.27) (P =.03). By fixing a cutoff
      score of 0.6, 10 (83%) of the 12 DAT patients showed baseline values below the
      cutoff, whereas 10 (71%) of 14 subjects who either developed non-Alzheimer-type
      dementia or maintained cognitive functions had values in the normal range.
      CONCLUSION: Mild cognitive impairment is a major risk factor for DAT, and
      Alzheimer disease-related pathological changes can be identified in patients
      converting to DAT within a 2-year follow-up.

PMID- 14676050
TI  - Cortical cholinergic function is more severely affected in parkinsonian dementia
      than in Alzheimer disease: an in vivo positron emission tomographic study.
AB  - BACKGROUND: Pathology reports have shown that cholinergic forebrain neuronal
      losses in parkinsonian dementia (PDem) are equal to or greater than those in
      Alzheimer disease (AD). We hypothesized that patients with PDem would have
      cholinergic deficits that were similar to or greater than those of patients with
      AD. OBJECTIVE: To determine in vivo cortical acetylcholinesterase (AChE) activity
      in healthy control subjects and in patients with mild AD, PDem, and Parkinson
      disease without dementia using AChE positron emission tomography. SETTING:
      University and Veterans' Administration medical center. Design and Patients Group
      comparison design of patients with AD (n = 12), PDem (n = 14), and Parkinson
      disease without dementia (n = 11), and controls (n = 10) who underwent AChE
      imaging between July 1, 2000, and January 31, 2003. Patients with AD and PDem had
      approximately equal dementia severity. MAIN OUTCOME MEASURES: Cerebral AChE
      activity. RESULTS: Compared with controls, mean cortical AChE activity was lowest
      in patients with PDem (-20.0%), followed by patients with Parkinson disease
      without dementia (-12.9%; P<.001). Mean cortical AChE activity was relatively
      preserved in patients with AD (-9.1%), except for regionally selective
      involvement of the lateral temporal cortex (-15%; P<.001). CONCLUSION: Reduced
      cortical AChE activity is more characteristic of patients with PDem than of
      patients with mild AD.

PMID- 14676051
TI  - Spinocerebellar ataxia type 14 caused by a mutation in protein kinase C gamma.
AB  - BACKGROUND: We previously discovered spinocerebellar ataxia type 14 (SCA14) in a
      single Japanese family with an autosomal dominant neurodegenerative disorder
      characterized by cerebellar ataxia and intermittent axial myoclonus. The latter
      manifestation is selectively observed in patients with early onset. We mapped the
      locus to chromosome 19q13.4-qter, but the etiologic gene was not known. Recently,
      a mutation in the protein kinase C gamma gene (PRKCG) was identified in a US
      family of English and Dutch ancestry with autosomal dominant SCA whose disease
      mapped to a region overlapping that of the SCA14 locus. Different PRKCG mutations
      were found in another family with SCA and in a sporadic case from the United
      States. Axial myoclonus was not observed in any of these US families. OBJECTIVES:
      To determine whether a mutation in the PRKCG gene is responsible for SCA14 and to
      investigate the prevalence of PRKCG mutations in Japanese patients with autosomal
      dominant SCA. PATIENTS AND METHODS: Direct nucleotide sequencing analysis of the
      18 coding exons of the PRKCG gene was performed in the 19 members of the original
      Japanese family with SCA14 and in 24 Japanese probands with SCA. After
      identifying a PRKCG mutation, DNA samples from 72 patients with multiple system
      atrophy and 50 healthy individuals were examined for the mutation as controls.
      RESULTS: Sequence analysis revealed a novel missense mutation, Gln127Arg, in all
      affected members of the family with SCA14. This mutation was not found in 122
      control individuals. No mutations in the PRKCG gene were detected in the group of
      24 probands with SCA of unknown type. CONCLUSIONS: These findings document that
      SCA14 is caused by mutations in the PRKCG gene. The observation that all 4 PRKCG
      mutations identified in patients with SCA to date are located in exon 4 suggests
      a critical role for this region of the gene in cerebellar function. Mutations in
      the same region of the gene can result in myoclonus in some families but not in
      others.

PMID- 14676052
TI  - Comparison of electrodiagnostic abnormalities and criteria in a cohort of
      patients with chronic inflammatory demyelinating polyneuropathy.
AB  - BACKGROUND: Current electrodiagnostic criteria for chronic inflammatory
      demyelinating polyneuropathy (CIDP) are research oriented favoring specificity
      over sensitivity. Application of such criteria in clinical practice may miss the
      diagnosis in potentially treatable patients. OBJECTIVES: To analyze the
      electrophysiologic abnormalities in a cohort of patients with clinically defined
      CIDP, to compare these data with published electrodiagnostic criteria, and to
      identify a set of abnormalities that is shared by all patients with CIDP. DESIGN:
      Retrospective medical record review. SETTING: Academically based neuromuscular
      clinic. Patients Fifteen patients with clinically diagnosed relapsing
      sensorimotor CIDP. INTERVENTIONS: Administration of intravenous immunoglobulin or
      prednisone. MAIN OUTCOME MEASURES: Electrodiagnostic studies. RESULTS: All
      patients had electrodiagnostic abnormalities in at least 3 nerves with possible
      partial conduction block or demyelinating range abnormalities in at least 1
      nerve. The diagnostic sensitivities of 5 published CIDP criteria were as follows:
      the Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force
      (40%), Saperstein et al (47%), Nicolas et al (53%), Hughes et al for the
      Inflammatory Neuropathy Cause and Treatment Group (60%), and Thaisetthawatkul et
      al (70%). CONCLUSIONS: Current electrodiagnostic criteria for CIDP are
      insensitive and may fail to diagnose the condition in a substantial number of
      patients. More inclusive criteria that allow identification of patients in
      routine clinical practice are needed.

PMID- 14676053
TI  - A comparison of clinical and radiological findings in adults and children with
      Japanese encephalitis.
AB  - BACKGROUND: Japanese encephalitis (JE) is the most common human endemic
      encephalitis, prevalent mainly in Southeast Asia. It affects both adults and
      children in different areas, but there is no comparative study of their clinical
      features and outcomes. OBJECTIVE: To evaluate clinical and radiological features
      in adults and children with JE. METHODS: Patients with serologically or
      virologically confirmed JE who were treated during the past 10 years were
      included in this study. All patients underwent a detailed neurological
      examination, computed tomography, or magnetic resonance imaging. The presence of
      movement disorders, anterior horn cell involvement, and electroencephalographic
      changes was noted. After 6 months, each patient's outcome was defined as poor,
      partial, or complete recovery. The clinical and radiological findings for both
      adults and children were compared using chi2 tests. RESULTS: The results are
      based on 30 children and 37 adults. Seizure was present in 23 adults (62.2%) and
      in 17 children (56.7%). Three children had associated neurocysticercosis, and all
      of them had partial seizures. The occurrence of focal neurological deficit,
      anterior horn cell involvement, and parkinsonian features was not significantly
      different between adults and children. Dystonia was more common in children,
      occurring in 20 (66.7%) compared with 7 adults (18.9%). Six adults died, but none
      of the children did; however, the 6-month outcome was better for surviving adults
      compared with the children. Computed tomography and magnetic resonance imaging
      findings were not significantly different between the 2 groups. CONCLUSIONS:
      Children with JE are more likely to have dystonia and a poor outcome at 6 months
      compared with adults. The difference in clinical findings and outcome in children
      and adults with JE may be owing to immunological factors, maturation of the
      central nervous system, and neuronal plasticity.

PMID- 14676054
TI  - Mutation screening of the ALS2 gene in sporadic and familial amyotrophic lateral
      sclerosis.
AB  - BACKGROUND: Mutations in the ALS2 gene cause juvenile-onset autosomal recessive
      amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia. OBJECTIVE:
      To assess the role of ALS2 among more common forms of ALS. METHODS: DNA from 95
      unrelated familial, 95 unrelated sporadic, and 11 early-onset ALS patients was
      screened for mutations in ALS2 by denaturing high-performance liquid
      chromatography and direct sequencing of polymerase chain reaction-amplified
      fragments. Each variant identified was also analyzed among control subjects. All
      34 exons of ALS2 plus the 5' and 3' untranslated region were screened. RESULTS:
      We detected 23 novel sequence variants; however, none is disease-associated.
      CONCLUSION: Mutations of ALS2 are not a common cause of ALS.

PMID- 14676055
TI  - Levetiracetam for phasic spasticity in multiple sclerosis.
AB  - BACKGROUND: Spasticity is a common and debilitating symptom of multiple sclerosis
      (MS). Current treatments are effective, but may be difficult to tolerate for many
      patients. OBJECTIVE: To determine if levetiracetam, a second-generation
      antiepileptic drug, may be useful for the treatment of spasticity in MS. METHODS:
      A retrospective medical record review of patients attending the Multiple
      Sclerosis Program at the University of Texas, Southwestern Medical Center at
      Dallas was performed. A series of 12 patients who had been treated with
      levetiracetam for spasticity was identified. Most of the patients were female
      (10/11), and the mean age was 41.0 years. The main outcome measure was a change
      in Penn spasm score or modified Ashworth score. Both scores are measured on a
      scale of 0 to 4. RESULTS: The Penn Spasm score (a measure of phasic spasticity)
      was decreased for all patients following treatment with levetiracetam. The mean
      +/- SD Penn Spasm score was 2.7 +/- 0.65 at baseline and decreased to 0.9 +/-
      0.29 at follow-up. There was no change in modified Ashworth scores (a measure of
      tonic spasticity). Five patients reported adverse events; 1 patient discontinued
      treatment owing to an adverse event (edema). Three patients incidentally reported
      improvements in neuropathic pain. CONCLUSIONS: Levetiracetam was effective for
      reducing phasic spasticity but not tonic spasticity in this 12-patient case
      series. The drug was well tolerated and therefore shows promise as a treatment
      for phasic spasticity. Large, well-controlled trials are needed to confirm these
      findings.

PMID- 14676056
TI  - Comparison of the short test of mental status and the mini-mental state
      examination in mild cognitive impairment.
AB  - BACKGROUND: The Mini-Mental State Examination (MMSE) is the most widely used
      brief screening measure of cognition, but it is not sensitive in detecting mild
      memory or other cognitive impairments. The Short Test of Mental Status (STMS) was
      specifically developed for use in dementia assessment and was intended to be more
      sensitive to problems of learning and mental agility that may be seen in mild
      cognitive impairment (MCI). OBJECTIVE: To compare the STMS and MMSE for detecting
      or predicting MCI. DESIGN: Comparison of STMS and MMSE scores at baseline among 4
      groups of patients: 788 patients with stable normal cognition, 75 patients with
      normal cognition at baseline but who developed incident MCI or Alzheimer disease
      during follow-up, 129 patients with prevalent MCI at baseline, and 235 patients
      with prevalent mild Alzheimer disease. All patients and control subjects for this
      study were evaluated through the Mayo Alzheimer's Disease Patient Registry or the
      Mayo Clinic Alzheimer's Disease Research Center, Rochester, Minn, using a
      standardized diagnostic approach. RESULTS: The STMS was slightly more sensitive
      than the MMSE in discriminating between patients with stable normal cognition and
      patients with prevalent MCI. The STMS was superior to the MMSE in detecting
      deficits in cognition in individuals who had normal cognition at baseline but
      later developed incident MCI or Alzheimer disease. CONCLUSIONS: Compared with the
      MMSE, the STMS was better able to document MCI and was more sensitive in
      detecting deficits in cognition in individuals who had normal cognition at
      baseline but later developed incident MCI or Alzheimer disease.

PMID- 14676057
TI  - Myelopathy due to copper deficiency following gastrointestinal surgery.
AB  - BACKGROUND: Ataxic myelopathy due to copper deficiency has been described in
      ruminant animals and is called swayback. Neurological manifestations due to
      inherited copper deficiency secondary to the failure of intestinal copper
      absorption is well recognized as Menkes disease. The neurological consequences of
      acquired copper deficiency in humans are not well described. OBJECTIVE: To report
      2 cases where patients developed a myelopathy with copper deficiency after
      gastrointestinal surgery.Patients Two patients developed a myelopathy many years
      after gastrointestinal surgery. Both had severe copper deficiency, which was the
      likely cause of the myelopathy. CONCLUSIONS: Acquired copper deficiency may
      present as a myelopathy. Gastrointestinal surgery and resulting decreased copper
      absorption may be causative.

PMID- 14676058
TI  - Anterior spinal artery syndrome complicated by the ondine curse.
AB  - BACKGROUND: Anterior spinal artery (ASA) syndrome results in motor palsy and
      dissociated sensory loss below the level of the lesion, accompanied by bladder
      dysfunction. When the cervical spine is involved, breathing disorders may be
      observed. OBJECTIVE: To describe the polysomnographic findings in a patient with
      cervical ASA syndrome complicated by a sleep breathing disorder. SETTING: Unit of
      neurology at a sleep center. Patient A 30-year-old man had an ischemic lesion
      that affected the anterior cervical spinal cord (C2-C6) bilaterally because of an
      ASA thrombosis. He developed ASA syndrome associated with respiratory impairment
      during sleep. RESULTS: The polysomnographic study during sleep showed a severe
      sleep disruption caused by continuous central apneas that appeared immediately
      after falling asleep. Treatment by intermittent positive pressure ventilation
      normalized the respiratory pattern and sleep architecture. CONCLUSIONS: The sleep
      breathing pattern was compatible with central alveolar hypoventilation due to
      automatic breathing control failure caused by a lesion of the reticulospinal
      pathway, which normally activates ventilatory muscles during sleep. This
      autonomic sleep breathing impairment resembles that found as a complication in
      patients who undergo spinothalamic tract cervical cordotomy for intractable pain.
      This surgical complication is known as the Ondine curse.

PMID- 14676059
TI  - Vasculitis of the spinal cord.
AB  - BACKGROUND: Vasculitis of the central nervous system is rare but well described.
      It affects the cerebral hemispheres predominantly and only exceptionally involves
      the spinal cord. OBJECTIVE: To describe a case of spinal cord vasculitis with
      unusual pathologic changes. DESIGN: Case report with clinicopathologic
      correlation. Case Description A young man developed leg weakness and sensory
      symptoms over several weeks. He had an asymmetric paraparesis with impaired
      vibration sense in the feet and a Romberg sign but no sensory level. The
      cerebrospinal fluid contained 123 white blood cells x103/ micro L, mostly
      lymphocytes, and a protein concentration of 52 mg/dL; oligoclonal bands were not
      detected, but the illness simulated multiple sclerosis. Magnetic resonance
      imaging scans of the spinal cord and brain were normal. His condition improved on
      several occasions with intravenous infusions of corticosteroid agents, but his
      neurologic signs gradually worsened over several months, and he acquired a
      thoracic sensory level and sphincteric abnormalities. An explosive preterminal
      illness occurred with paraplegia, nystagmus, and coma. The findings of a
      pathologic examination showed numerous ischemic areas in the spinal cord, some
      cavitated, and a vasculitis of the leptomeningeal branches of the anterior spinal
      artery and of subpial vessels. The vessel walls were not necrotic, but many of
      their lumens were occluded by fibrinous material. There were similar findings in
      regions of cerebral hemorrhagic infarction. CONCLUSIONS: A destructive and
      vasculitic process should be considered in cases of subacute myelopathy with
      persistent cellular reaction in the cerebrospinal fluid and clinical
      responsiveness to corticosteroid therapy. The magnetic resonance imaging scan of
      the spinal cord may be normal.

PMID- 14676061
TI  - Generalized calcium deposition with intracranial surgical lesion.

PMID- 14676060
TI  - Metronidazole-induced encephalopathy and inferior olivary hypertrophy: lesion
      analysis with diffusion-weighted imaging and apparent diffusion coefficient maps.
AB  - BACKGROUND: Although several cases of metronidazole-induced encephalopathy have
      been reported, to our knowledge, there is no previous report of brain changes in
      anterior commissure, basal ganglia, cerebellar white matter, and inferior olivary
      nuclei on magnetic resonance images. The precise mechanisms of action of
      metronidazole-induced encephalopathy have not been determined. OBJECTIVES: To
      report a unique case of metronidazole-induced encephalopathy extensively
      involving multiple lesions and to determine the precise mechanism of action of
      metronidazole-induced encephalopathy. SETTING: University hospital. Patient A 74
      year-old woman hospitalized with complaints of progressive dysarthria, dysphagia,
      and gait disturbance 3 months after the initiation of metronidazole therapy.
      Intervention Brain magnetic resonance imaging and discontinuation of
      metronidazole therapy. Main Outcome Measure We observed changes of multiple
      lesions found on magnetic resonance imaging and analyzed apparent diffusion
      coefficient map values. RESULTS: Initial fluid-attenuated inversion recovery
      brain magnetic resonance images showed high signal intensities in diffuse
      subcortical white matter, anterior commissure, splenium, basal ganglia, midbrain,
      cerebellar white matter, and bilateral inferior olivary nuclei. These lesions
      were resolved after discontinuation of metronidazole therapy. However, the
      lesions in the inferior olivary nuclei were not resolved; rather they became
      hypertrophic. Apparent diffusion coefficient map values in the symptom period
      decreased and were normalized after discontinuation of metronidazole therapy.
      CONCLUSIONS: We describe a patient with metronidazole-induced encephalopathy
      involving reversible lesions in the anterior commissure, basal ganglia, and
      cerebellar white matter, which have not been reported previously. We observed
      inferior olivary hypertrophy, believed to be the result of lesions in the
      midbrain and cerebellar white matter rather than the result of lesions induced by
      metronidazole therapy. By using diffusion-weighted imaging and apparent diffusion
      coefficient maps, we found that metronidazole-induced encephalopathy might be
      caused by cytotoxic edema.

PMID- 14676062
TI  - Subconjunctival hemorrhages secondary to hypersympathetic state after a small
      diencephalic hemorrhage.

PMID- 14676063
TI  - The headaches of Alexander Graham Bell.

PMID- 14676064
TI  - The uncertain nosology of Hashimoto encephalopathy.

PMID- 14676065
TI  - Mycoplasma pneumoniae infection as a treatable cause of brainstem encephalitis.

PMID- 14676066
TI  - Parkinson disease with old-age onset.

PMID- 14676067
TI  - Clinical characteristics of late-onset Parkinson disease.

PMID- 14676068
TI  - Severe hidradenitis suppurativa treated with infliximab infusion.

PMID- 14676069
TI  - Increased detection of rickettsialpox in a New York City hospital following the
      anthrax outbreak of 2001: use of immunohistochemistry for the rapid confirmation
      of cases in an era of bioterrorism.
AB  - BACKGROUND: Rickettsialpox is a self-limited febrile illness with skin lesions
      that may be mistaken for signs of potentially more serious diseases, such as
      cutaneous anthrax or chickenpox. The cluster of cutaneous anthrax cases from
      bioterrorism in October 2001 likely heightened awareness of and concern for
      cutaneous eschars. OBJECTIVES: To apply an immunohistochemical technique on
      paraffin-embedded skin biopsy specimens for diagnosing rickettsialpox, and to
      compare the reported incidence of rickettsialpox before, during, and after the
      cluster of cutaneous anthrax cases. DESIGN: Case series. SETTING: Dermatology
      department in a large tertiary care hospital in New York City. PATIENTS: Eighteen
      consecutive patients with the clinical diagnosis of rickettsialpox from February
      23, 2001, through October 31, 2002. MAIN OUTCOME MEASURES: Results of
      immunohistochemical testing of skin biopsy specimens and of serological testing.
      RESULTS: Immunohistochemical testing revealed spotted fever group rickettsiae in
      all 16 eschars and in 5 of the 9 papulovesicles tested. A 4-fold or greater
      increase in IgG antibody titers reactive with Rickettsia akari was observed in
      all 9 patients for whom acute and convalescent phase samples were available; 6
      patients had single titers indicative of rickettsialpox infection (> or =1:64).
      Of the 18 patients, 9 (50%) presented in the 5 months following the bioterrorism
      attacks. CONCLUSIONS: Rickettsialpox remains endemic in New York City, and the
      bioterrorism attacks of October 2001 may have led to increased awareness and
      detection of this disease. Because rickettsialpox may be confused with more
      serious diseases, such as cutaneous anthrax or chickenpox, clinicians should be
      familiar with its clinical presentation and diagnostic features.
      Immunohistochemical staining of skin biopsy specimens, particularly from eschars,
      is a sensitive technique for confirming the clinical diagnosis.

PMID- 14676070
TI  - Histopathologic features of alopecia areata: a new look.
AB  - BACKGROUND: A peribulbar lymphocytic infiltrate is the expected histologic
      feature of alopecia areata, but it is absent in many scalp biopsy specimens.
      Other diagnostic criteria are needed. OBJECTIVE: To establish the histologic
      features of alopecia areata in scalp biopsy specimens taken from different types
      of alopecia areata, using follicular counts to relate biopsy findings to stages
      of the disease. METHODS: Fifty consecutive new patients with alopecia areata were
      studied. Four-millimeter punch biopsy specimens were taken from the scalp in
      areas of recent, active hair loss; old, inactive hair loss; or recent hair
      regrowth. Specimens were sectioned horizontally. Terminal and vellus-like hairs
      were counted. Inflammation and fibrosis around lower and upper follicles were
      rated. RESULTS: The histopathologic features of alopecia areata were not
      significantly affected by the sex, age, and race of the patient or by the type,
      percentage of hair loss, total duration, or regression of alopecia areata. The
      major factor affecting the histopathologic features was the duration of the
      current episode of alopecia areata. In the acute stage, bulbar lymphocytes
      surrounded terminal hairs in early episodes and miniaturized hairs in repeated
      episodes. In the subacute stage, decreased anagen and increased catagen and
      telogen hairs were characteristic. In the chronic stage, decreased terminal and
      increased miniaturized hairs were found, with variable inflammation. During
      recovery, increasing numbers of terminal anagen hairs from regrowth of
      miniaturized hairs and a lack of inflammation were noted. CONCLUSIONS: The
      histopathologic features of alopecia areata depend on the stage of the current
      episode. Alopecia areata should be suspected when high percentages of telogen
      hairs or miniaturized hairs are present, even in the absence of a peribulbar
      lymphocytic infiltrate.

PMID- 14676071
TI  - Treatment of psoriasis with alefacept: correlation of clinical improvement with
      reductions of memory T-cell counts.
AB  - OBJECTIVE: To examine the relationship between the pharmacodynamic and
      antipsoriatic effects of alefacept, a biologic agent that targets CD4+ and CD8+
      memory T cells. DESIGN: Randomized, double-blind, placebo-controlled study of 3
      parallel groups. SETTING: Fifty-one study centers. PATIENTS: Five hundred fifty
      three patients with chronic plaque psoriasis. INTERVENTIONS: Patients were
      randomized (1:1:1) to 1 of the following 3 cohorts: alefacept, 7.5 mg, in both
      courses (cohort 1); alefacept, 7.5 mg, in the first course and placebo in the
      second course (cohort 2); or placebo in the first course and alefacept, 7.5 mg,
      in the second course (cohort 3). In each course, alefacept or placebo was
      administered by intravenous bolus once weekly for 12 weeks, followed by 12 weeks
      of observation. MAIN OUTCOME MEASURES: Circulating lymphocyte levels and the
      Psoriasis Area Severity Index. RESULTS: One or 2 courses of alefacept reduced
      CD4+ and CD8+ memory T-cell counts, while sparing the naive population. At 12
      weeks after the last dose of alefacept in courses 1 and 2, 88% and 83% of
      patients, respectively, had CD4+ cell counts greater than the lower limit of
      normal. In course 1, alefacept-treated patients with the largest decreases in
      memory T-cell counts experienced the greatest reductions in disease activity
      (P<.001). The duration of clinical benefit seemed to be longer among patients who
      had the greatest reduction in CD4+ and CD8+ memory T-cell counts. CONCLUSIONS:
      One or 2 courses of intravenous alefacept reduced circulating memory T-cell
      counts while sparing the naive T-cell population. The reductions in memory T-cell
      counts were related to all measures of disease activity evaluated and the
      duration of response to therapy, suggesting that prolonged remissions of
      psoriasis can be attained with reduction of the pathogenic T-cell count.

PMID- 14676072
TI  - Improved sensitivity of T-cell clonality detection in mycosis fungoides by hand
      microdissection and heteroduplex analysis.
AB  - BACKGROUND: The presence of a dominant T-cell clone is an important diagnostic
      criterion in cutaneous T-cell lymphomas (CTCLs) and in atypical T-cell cutaneous
      infiltrates. Procedures based on polymerase chain reaction (PCR) are the most
      sensitive to detect clonality, but heteroduplex analysis is less sensitive than
      other methods such as denaturing gradient gel electrophoresis. OBJECTIVE: To
      assess whether a gross hand microdissection of the superficial (papillary)
      portion of the dermal infiltrate may improve the sensitivity of T-cell clonality
      detection by PCR-heteroduplex analysis in CTCL. SETTING: Regional university
      hospital (secondary or tertiary referral center). Patients A total of 29 patients
      with a definite diagnosis of mycosis fungoides based on typical histologic and
      immunophenotypic features were selected with patch (16) or plaque (13) stages.
      MAIN OUTCOME MEASURES: Assessment of T-cell clonality by PCR amplification of the
      T-cell receptor gamma chain followed by heteroduplex analysis using DNA extracted
      from the entire biopsy specimen and after gross microdissection of the
      subepidermal bandlike dermal infiltrate. RESULTS: T-cell clonality was
      demonstrated in 24 of 29 cases when hand microdissection was used compared with
      16 of 29 cases with DNA analysis from entire biopsy specimens; thus, hand
      microdissection resulted in a sensitivity improvement of approximatively 50%.
      CONCLUSIONS: Hand microdissection substantially improves the detection of a T
      cell clone in CTCL when using a PCR-heteroduplex analysis and could be used
      routinely in the clinical evaluation of T-cell infiltrates. Importantly, the
      microdissection method was found to be more useful for the detection of T-cell
      clones in early patch stages of CTCL than in plaque-stage disease.

PMID- 14676074
TI  - Safety of cyclooxygenase 2 inhibitors and increased leukotriene synthesis in
      chronic idiopathic urticaria with sensitivity to nonsteroidal anti-inflammatory
      drugs.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) exacerbate various
      forms of urticaria by a nonallergic mechanism involving inhibition of
      cyclooxygenases. OBJECTIVES: To assess safety of cyclooxygenase inhibitors in
      patients with chronic idiopathic urticaria (CIU) and NSAID sensitivity and to
      evaluate a role of cysteinyl leukotriene metabolism and mast cell activation in
      sensitivity to NSAIDs in CIU. DESIGN: Aspirin challenge test followed by
      randomized, prospective, double-blind, placebo-controlled crossover trial with
      cyclooxygenase 2 inhibitors. SETTING: Tertiary referral center of a university
      hospital. PATIENTS: Thirty-six patients with CIU. INTERVENTIONS: Aspirin
      challenge test (up to 500 mg); randomized trial with rofecoxib (up to 37.5 mg)
      and celecoxib (up to 300 mg) in aspirin-sensitive patients. After completion of
      the trial, 7 patients received naproxen sodium (500 mg) as a positive control.
      MAIN OUTCOME MEASURES: Standardized skin examination, skin biopsy with mast cell
      count, urinary levels of leukotriene E4 (LTE4), and serum levels of mast cell
      tryptase. RESULTS: Aspirin induced skin eruption in 18 patients. Rofecoxib or
      celecoxib did not elicit skin eruption in any of the aspirin-sensitive patients.
      Patients with CIU had higher urinary excretion of LTE4 than healthy control
      subjects. Basal urinary levels of LTE4 and serum mast cell tryptase were
      increased in aspirin-sensitive compared with aspirin-tolerant patients. Severity
      and duration of aspirin-induced urticaria showed a positive correlation with
      urinary LTE4 excretion. Naproxen precipitated urticaria in 5 of 7 aspirin
      sensitive patients and caused further increase in urinary LTE4. CONCLUSIONS:
      Cyclooxygenase 2 inhibitors do not induce urticaria in patients with CIU
      sensitive to NSAIDs. Sensitivity to NSAIDs in CIU is associated with
      overproduction of cysteinyl leukotrienes and mast cell activation and most likely
      depends on inhibition of cyclooxygenase 1.

PMID- 14676075
TI  - Radiotherapy alone for primary Merkel cell carcinoma.
AB  - BACKGROUND: Merkel cell carcinoma is a rare and potentially aggressive cancer of
      the skin. Cumulative data from small retrospective series have supported
      treatment by wide excision and adjuvant radiotherapy. However, wide excision may
      be difficult to perform in patients with tumors of the head and neck or in older
      populations with comorbidities that may be incompatible with general anesthesia.
      OBSERVATIONS: Nine patients (group 1) with stage I (without lymph node
      involvement) Merkel cell carcinoma primary tumors were treated in our center by
      radiotherapy alone. The rate of recurrence was compared between this group and 17
      additional patients (group 2) with stage I Merkel cell carcinoma who received
      conventional treatment (surgery followed by radiotherapy). RESULTS: The median
      follow-up was 3.0 years (range, 8 months to 7 years) for group 1 and 4.6 years
      (range, 5 months to 11 years) for group 2. During this period, we observed 1
      relapse and 1 progression of disease in group 2. No statistical difference was
      found in overall and disease-free survival between the 2 groups of patients.
      CONCLUSION: This study demonstrates the possibility of treating inoperable Merkel
      cell carcinoma by radiotherapy alone, with outcomes similar to those of classic
      treatment.

PMID- 14676077
TI  - Clinical and pathologic correlations in genetically distinct forms of atrichia.
AB  - BACKGROUND: The genetic basis of 2 distinct forms of atrichia with papules has
      recently been defined at the molecular level. In atrichia with papular lesions
      (APL; Online Mendelian Inheritance in Man [OMIM] 209500), mutations in the
      hairless gene on chromosome 8p21 have recently been identified. Atrichia with
      papules also occurs in the clinical setting of vitamin D-dependent rickets type
      IIA (VDDR IIA; OMIM 277440), resulting from mutations in the vitamin D receptor
      gene on chromosome 12q12-q14. Despite the distinct genetic basis for both forms
      of atrichia, the clinical findings are strikingly similar and exhibit classic
      pathognomonic features unique to this phenotype. We sought to document the
      clinical and molecular features of APL and VDDR IIA. OBSERVATIONS: Molecular
      analysis of the hairless and vitamin D receptor genes was performed on genomic
      DNA from probands and family members from 3 families with APL and 2 with VDDR
      IIA. We present a clinical and histologic comparison of atrichia in patients with
      APL and VDDR IIA and highlight the genetically heterogeneous basis of atrichia by
      identification of pathogenetic mutations. CONCLUSIONS: Increased awareness of
      these diseases will allow early diagnosis and potential therapeutic intervention
      for the rickets in VDDR IIA and avoidance of treatment of the atrichia in both
      APL and VDDR IIA. Their phenotype similarities suggest the possibility of a
      functional relationship between HR and VDR.

PMID- 14676078
TI  - CD4+ T-lymphocyte-induced Epstein-Barr virus reactivation in a patient with
      severe hypersensitivity to mosquito bites and Epstein-Barr virus-infected NK cell
      lymphocytosis.
AB  - BACKGROUND: Natural killer (NK) cell lymphocytosis associated with Epstein-Barr
      virus (EBV) infection often shows severe hypersensitivity to mosquito bites (HMB)
      characterized by intense local skin reactions and systemic symptoms such as high
      fever, lymphadenopathy, and hepatosplenomegaly. However, the induction mechanism
      of HMB is still unclear. OBSERVATIONS: We investigated a typical case of HMB with
      EBV-positive NK cell lymphocytosis. CD4+ T cells dominantly infiltrated the site
      of the mosquito bite, while EBV-positive cells were few in comparison. CD4+ T
      cells, but not CD8+ T cells or NK cells, responded to the mosquito salivary gland
      extracts. Interestingly, coculturing of the NK cells and CD4+ T cells activated
      by mosquito extracts induced expression of EBV lytic-cycle proteins in the NK
      cells. Furthermore, the expression of BZLF1, a viral lytic-cycle transactivator,
      was detectable at the skin lesion induced by scratch patch testing with mosquito
      extract. The EBV DNA copy number levels in the plasma were elevated in systemic
      HMB symptoms compared with the normal condition. CONCLUSIONS: CD4+ T cells are
      important for the primary skin reaction to mosquito bites and might play a key
      role in reactivation of latent EBV infection in NK cells. This viral reactivation
      contributed to the pathogenesis of the infectious mononucleosis-like systemic
      symptoms of HMB in our present case.

PMID- 14676079
TI  - Linear arrangement of multiple deep penetrating nevi: report of first case and
      review of literature.
AB  - BACKGROUND: Deep penetrating nevus is a recently described variant of melanocytic
      nevi with clinical and histopathological features that may be confused with
      malignant melanoma, blue nevus, pigmented Spitz nevus, or congenital melanocytic
      nevus. We report a case with linear arrangement of multiple deep penetrating
      nevi. To our knowledge, such presentation has never been reported in the
      literature. OBSERVATIONS: We describe a patient with multiple darkly pigmented
      lesions in the right periauricular area, above and behind the ear. The
      histopathological features of these lesions were consistent with deep penetrating
      nevus. CONCLUSIONS: To our knowledge, this is the first report of linear
      arrangement of multiple deep penetrating nevi. We consider this case a unique
      presentation of deep penetrating nevus.

PMID- 14676080
TI  - French people and skin diseases: results of a survey using a representative
      sample.
AB  - OBJECTIVE: To evaluate, from the patients' viewpoint, the prevalence, management,
      and impact of main dermatologic disorders in France. DESIGN: Survey conducted
      from March 28 to May 6, 2002, with the Sofres Taylor Nelson Institute on 10,000
      households using 1 questionnaire per household. SETTING: General community.
      PATIENTS: A total of 25,441 subjects from 10,000 households determined to be
      representative of the French population and regularly surveyed by the Taylor
      Nelson Sofres Institute. MAIN OUTCOME MEASURES: Estimation of the prevalence of
      skin disorders by the French population. RESULTS: Of the 10 000 households, 7466
      (74.7%) returned the questionnaire, which was completed for 18,137 (71.3%) of the
      25,441 subjects. Of those, 15,742 reported having had skin problems since birth,
      or, by extrapolation, 86.8% (47.29 million) of the French population; 7841
      reported having had skin problems in the past 24 months, or, by extrapolation,
      43.2% (23.53 million) of the French population; and 28.7% said that their skin
      problems impaired their daily life. However, 61% of the sample were satisfied
      with their dermatologist. CONCLUSION: This survey of perceived health status in
      France highlights both the prevalence of skin disorders and the underestimation
      of the effects of dermatologic disorders in public health. A majority of the
      French population is satisfied with the care supplied by dermatologists.

PMID- 14676081
TI  - Cutaneous melanomas associated with nevi.
AB  - OBJECTIVE: To determine the frequency of and the histologic and clinical factors
      associated with melanoma existing in histologic contiguity with a nevus. DESIGN:
      Pathology reports from melanomas collected from January 1, 1993, to December 31,
      1997, were retrospectively reviewed. SETTING: Independent, community-based
      dermatopathology laboratory. PATIENTS: A total of 1606 patients with a histologic
      diagnosis of melanoma. INTERVENTION: None. MAIN OUTCOME MEASURES: Differences in
      histologic (subtype, Breslow thickness, and Clark level) and clinical (age, sex,
      and anatomic location) features between melanomas that are associated and
      unassociated with a nevus. RESULTS: Twenty-six percent of the melanomas reviewed
      were histologically associated with nevi (dysplastic nevi, 43.0%; and other nevi,
      57.0%). Factors that were significantly associated with an increased likelihood
      of a melanoma being histologically contiguous with a nevus included younger age,
      superficial spreading subtype, truncal location, Breslow thickness, and Clark
      level. However, after multivariate analysis, only younger age (odds ratio, 1.27;
      95% confidence interval, 1.19-1.37), superficial spreading subtype (odds ratio,
      2.96; 95% confidence interval, 2.17-4.02), and truncal location (odds ratio,
      3.26; 95% confidence interval, 2.55-4.19) remained significant. CONCLUSIONS: Most
      melanomas were not histologically contiguous with a nevus. Younger age,
      superficial spreading subtype, and truncal location are independent significant
      predicators of a melanoma being histologically associated with a nevus.

PMID- 14676082
TI  - A randomized trial of etanercept as monotherapy for psoriasis.
AB  - OBJECTIVE: To determine safety and efficacy of monotherapy with etanercept.
      DESIGN: Randomized, double-blind, placebo-controlled, multicenter study. SETTING:
      Outpatient, ambulatory; private practice and university dermatology research
      centers. PATIENTS: Patients aged at least 18 years, with plaque psoriasis
      involving 10% or more of body surface area; 148 were screened and 112 were
      randomly assigned to treatment groups and received study drug. INTERVENTIONS:
      Patients received placebo or etanercept, 25 mg, subcutaneously twice a week for
      24 weeks. Other psoriasis therapies were limited during the study. MAIN OUTCOME
      MEASURES: Safety measurements included tracking of adverse events and laboratory
      values. Efficacy was evaluated using the Psoriasis Area and Severity Index
      (PASI); the primary end point was a 75% improvement in PASI. Other efficacy
      measurements included patient and physician global assessments and quality-of
      life measures. RESULTS: After 12 weeks of treatment, 17 (30%) of the 57
      etanercept-treated patients and 1 (2%) of the 55 placebo-treated patients had
      achieved PASI 75%, and after 24 weeks, 32 (56%) of etanercept-treated patients
      and 3 (5%) of placebo-treated patients had reached this level (P<.001 for both
      time points). By 24 weeks, psoriasis was clear or minimal by physician's global
      assessment in more than 50% of patients who received etanercept. Treatment
      failure (PASI response <50) occurred in 23% of patients at week 24. All other
      measures confirmed the efficacy of etanercept. Adverse events were similar among
      etanercept and placebo groups. CONCLUSION: Etanercept monotherapy provided
      significant benefit to patients with psoriasis and had a favorable safety
      profile.

PMID- 14676083
TI  - Adjuvant high-dose interferon therapy for high-risk melanoma.

PMID- 14676085
TI  - Merkel cell carcinoma treatment with radiation: a good case despite no
      prospective studies.

PMID- 14676086
TI  - Infants with "hair today that's gone tomorrow": an inherited atrichia?

PMID- 14676087
TI  - A 63-year-old man with chronic penile ulcers.

PMID- 14676088
TI  - Pruritic erythematous macules in a 72-year-old woman.

PMID- 14676089
TI  - Soft nodules at the tip of the tongue of a 26-year-old man.

PMID- 14676090
TI  - Tender subcutaneous nodules in a patient with AIDS.

PMID- 14676091
TI  - Effects of inflammatory arthritis on quality of life in patients with psoriasis.

PMID- 14676093
TI  - Bioterrorism preparedness in the dermatology community.

PMID- 14676092
TI  - Calcipotriene and vitiligo.

PMID- 14676094
TI  - Iguana bite-induced hypersensitivity reaction.

PMID- 14676095
TI  - An unusual presentation of a cutaneous odontogenic sinus.

PMID- 14676098
TI  - Dermoscopy of melanocytic neoplasms: subpatterns of dysplastic/atypical nevi.

PMID- 14676099
TI  - Lustrous insights into cisplatin accumulation: copper transporters.

PMID- 14676100
TI  - Rituximab: converging mechanisms of action in non-Hodgkin's lymphoma?

PMID- 14676101
TI  - Targeting the epidermal growth factor receptor in non-small cell lung cancer.
AB  - Fifteen% or fewer of patients with non-small cell lung cancer (NSCLC) survive 5
      years. The current standard of care for patients with locally advanced or
      metastatic NSCLC is systemic chemotherapy with a two-drug combination regimen
      that includes a platinum agent. Although systemic chemotherapy reduces the rate
      of death attributable to lung cancer, disease progression is inevitable and dose
      limiting toxicities restrict their use. New molecularly targeted therapies aim to
      inhibit specific pathways and key molecules implicated in tumor growth and
      progression while sparing normal cells. Several therapies, which target signal
      transduction pathways involved in angiogenesis, metastasis, and apoptosis, are in
      clinical development to treat lung cancer. Among these targeted therapies are the
      oral, small-molecule epidermal growth factor receptor-tyrosine kinase (EGFR-TK)
      inhibitors gefitinib and erlotinib. Both therapies have been validated
      preclinically as new treatment approaches for NSCLC and have shown single-agent
      activity against advanced, chemorefractory NSCLC in clinical trials. This article
      focuses on the biology of the EGFR-TK signal transduction pathway, its role in
      the proliferation of solid tumors, and the rationale for the clinical development
      of EGFR-TK inhibitors. We also review clinical trials with EGFR-TK inhibitors in
      NSCLC and future directions of investigation with these targeted agents.

PMID- 14676102
TI  - Is KIT an important therapeutic target in small cell lung cancer?

PMID- 14676103
TI  - Crossover randomized comparison of intravenous versus intravenous/oral mesna in
      soft tissue sarcoma treated with high-dose ifosfamide.
AB  - PURPOSE: We conducted our study to determine the pharmacokinetics (PK) and
      clinical efficacy of oral mesna in patients receiving ifosfamide for soft tissue
      sarcoma. EXPERIMENTAL DESIGN: Seventeen patients were enrolled in a randomized
      prospective Phase I/II study. Seventeen patients were exposed to study
      medication. Ifosfamide was given at a dose of 2 g/m2/day for 5 days on a 21-day
      cycle. Before the first cycle, all patients were randomized onto a crossover
      design and received either the approved i.v. or i.v./oral mesna regimen, with
      crossover for the second cycle of chemotherapy. The i.v. mesna regimen consisted
      of dosings (20% ifosfamide dose) at 0, 4, and 8 h. The i.v./oral arm consisted of
      an i.v. mesna dosing (20% ifosfamide dose) at 0 h, followed by oral tablet dosing
      (40% ifosfamide dose) at 2 and 6 h. In-patient clinical monitoring and phlebotomy
      and urine sampling for mesna, dimesna, and ifosfamide PK were performed on all
      chemotherapy days. RESULTS: Thirteen patients were evaluable for PK and 17 for
      efficacy and toxicity. No significant differences were detected in the plasma PK
      of the concomitantly infused ifosfamide. Rates of hemorrhagic cystitis were
      similar across mesna schedules. Four of 10 evaluable patients demonstrated
      objective response. CONCLUSION: On the basis of our study, an i.v./oral mesna
      regimen is at least as uroprotective as the approved i.v. regimen. The i.v./oral
      regimen will improve patient tolerance and convenience, allow for a reduction in
      elective hospitalizations for ifosfamide chemotherapy, reduce the potential
      morbidity associated with inpatient administration of chemotherapy, and likely
      result in decreased costs of care.

PMID- 14676104
TI  - Celecoxib modulates the capacity for prostaglandin E2 and interleukin-10
      production in alveolar macrophages from active smokers.
AB  - PURPOSE: Preclinical data suggest that the cyclooxygenase (COX)-2/prostaglandin
      (PG) E2 signaling pathway plays an essential role in conferring the malignant
      phenotype in non-small cell lung cancer. We hypothesized that treatment with oral
      celecoxib, a selective COX-2 inhibitor, would favorably alter biomarkers of lung
      cancer risk. This study evaluated the feasibility of COX-2 inhibition as a form
      of chemoprevention for lung cancer. EXPERIMENTAL DESIGN: Heavy active smokers
      were enrolled into a pilot study and treated with celecoxib. Bronchoscopy with
      bronchoalveolar lavage was performed both before and after 1 month of celecoxib
      treatment to recover alveolar macrophages (AMs) and lining fluid for study. After
      harvest, AMs were immediately stimulated in vitro with the calcium ionophore
      A23187. AMs obtained from smokers before treatment and from nonsmoking control
      subjects were also cultured overnight with SC58236, a selective COX-2 inhibitor,
      with or without lipopolysaccharide stimulation. RESULTS: Treatment with celecoxib
      significantly reduced calcium ionophore-stimulated PGE2 production from AMs
      recovered from smokers. AMs recovered from smokers, but not nonsmokers, were
      primed to produce high levels of PGE2 and interleukin (IL-10) when stimulated
      with lipopolysaccharide, and SC58236 significantly abrogated the production of
      these factors. Moreover, both plasma and bronchoalveolar lavage fluid obtained
      from treated subjects significantly reduced the production of PGE2 that resulted
      when a lung cancer cell line, A549, was stimulated with IL-1beta or A23187.
      CONCLUSIONS: Our findings suggest that oral celecoxib is capable of inhibiting
      the overproduction of PGE2, as well as modulating the production of IL-10 in the
      lung microenvironment in individuals at risk for lung cancer.

PMID- 14676105
TI  - A Phase I trial of 90Y-anti-carcinoembryonic antigen chimeric T84.66
      radioimmunotherapy with 5-fluorouracil in patients with metastatic colorectal
      cancer.
AB  - PURPOSE: Targeted systemic radiation therapy using radiolabeled antibodies
      results in tumor doses sufficient to produce significant objective responses in
      the radiosensitive hematological malignancies. Although comparable doses to tumor
      are achieved with radioimmunotherapy (RIT) in solid tumors, results have been
      modest primarily because of their relative lack of radiosensitivity. For solid
      tumors, as with external beam radiotherapy, RIT should have a more important
      clinical role if combined with other systemic, potentially radiation-enhancing
      chemotherapy agents and if used as consolidative therapy in the minimal tumor
      burden setting. The primary objective of this trial was to evaluate the
      feasibility and toxicities of systemic 90Y-chimeric T84.66 (cT84.66) anti
      carcinoembryonic antigen RIT in combination with continuous infusion 5
      fluorouracil (5-FU). EXPERIMENTAL DESIGN: Patients with chemotherapy-refractory
      metastatic colorectal cancer were entered. The study was designed for each
      patient to receive 90Y-cT84.66 anti-carcinoembryonic antigen at 16.6 mCi/m2 as an
      i.v. bolus infusion combined with 5-FU delivered as a 5-day continuous infusion
      initiated 4 h before antibody infusion. Cohorts of patients were entered at 5-FU
      dose levels of 700, 800, 900, and 1000 mg/m2/day. Upon reaching the highest
      planned dose level of 5-FU, a final cohort received 90Y-cT84.66 at 20.6 mCi/m2
      and 5-FU at 1000 mg/m2/day. For all patients, Ca-diethylenetriaminepentaacetic
      acid at 125 mg/m2 every 12 h was administered for the first 72 h after 90Y
      cT84.66. Patients were eligible to receive up to three cycles of 90Y-cT84.66/5-FU
      every 6 weeks. RESULTS: Twenty-one patients were treated on this study. All had
      been heavily pretreated with 19 having previously received 5-FU and 16 having
      failed two to four chemotherapy regimens. A maximum-tolerated dose of 16.6 mCi/m2
      90Y-cT84.66 combined with 1000 mg/m2/day 5-FU was reached. These dose levels are
      comparable with maximum-tolerated dose levels of each agent alone. Thirteen
      patients received one cycle and 8 patients two cycles of therapy. Hematopoietic
      toxicity was dose-limiting and reversible. RIT did not appear to increase
      nonhematopoietic toxicities associated with 5-FU. Two of 19 patients assayed
      developed a human anti-chimeric antibody immune response after the first cycle of
      therapy, which is significantly less than that observed in a previous trial
      evaluating 90Y-cT84.66 alone. No objective responses were observed. However, 11
      patients with progressive disease entering the study demonstrated radiological
      stable disease of 3-8 months duration and 1 patient demonstrated a mixed
      response. CONCLUSIONS: Results from this trial are encouraging and demonstrate
      the feasibility and possible advantages of combining continuous infusion 5-FU
      with 90Y-cT84.66 RIT. The addition of 5-FU does not appear to significantly
      enhance hematological toxicities of the radiolabeled antibody. In addition, 5-FU
      reduces the development of human anti-chimeric antibody response, permitting
      multicycle therapy in a larger number of patients. Future efforts should continue
      to focus on integrating radiation therapy delivered by radiolabeled antibodies
      into established 5-FU regimens.

PMID- 14676106
TI  - Increase in expression of the copper transporter ATP7A during platinum drug-based
      treatment is associated with poor survival in ovarian cancer patients.
AB  - PURPOSE: The Cu efflux transporter ATP7A is overexpressed in some cisplatin
      resistant ovarian carcinoma cell lines. We examined the expression of ATP7A in
      the major normal human organs and in several types of human malignancies and
      sought to determine whether ATP7A expression changed during treatment of ovarian
      carcinomas with Pt-containing regimens. EXPERIMENTAL DESIGN: ATP7A expression was
      quantified by immunohistochemical staining using microarrays containing normal
      and malignant tissues, and standard sections of 54 paired tumor samples obtained
      from ovarian carcinoma patients before and after at least two cycles of platinum
      based therapy. RESULTS: ATP7A was expressed in normal endometrium, prostate,
      testis, and kidney but was not detected in the other major organs. ATP7A was
      expressed in some of the most common human malignancies, including prostate (7 of
      7), breast (10 of 10), lung (8 of 8), colon (5 of 8), and ovary (6 of 7), as well
      as in a wide variety of other types of malignancy. ATP7A staining was detected in
      28 of 54 ovarian carcinomas before treatment. Patients with increased ATP7A
      expression after treatment (18 of 54) exhibited poorer actuarial survival
      (P<0.0057 by log-rank test). Expression of ATP7A either before or after treatment
      was not associated with other clinical factors. CONCLUSIONS: Although ATP7A is
      not detectable in most normal tissues it is expressed in a considerable fraction
      of many common tumor types. Enrichment of the tumor for ATP7A-expressing cells
      during platinum drug-based treatment of ovarian cancers is associated with poor
      survival. These findings are in agreement with results of in vitro studies from
      this laboratory demonstrating that increased expression of ATP7A renders cells
      resistant to cisplatin and carboplatin.

PMID- 14676107
TI  - The folate pool in colorectal cancers is associated with DNA hypermethylation and
      with a polymorphism in methylenetetrahydrofolate reductase.
AB  - PURPOSE: Aberrant DNA methylation occurs in a subset of colorectal cancers and is
      characterized by regional areas of hypermethylation at CpG islands. The aims of
      this study were firstly to evaluate the levels of folate intermediates (FIs) in
      tumors with aberrant DNA methylation and secondly to determine whether these
      levels are affected by polymorphisms in key genes involved in folate metabolism.
      EXPERIMENTAL DESIGN: The concentrations of two major intracellular FIs, 5,10
      methylenetetrahydrofolate and tetrahydrofolate (FH4), were measured in 103
      surgically resected colorectal cancers. DNA hypermethylation at seven different
      CpG islands was measured using the MethylLight assay. Genotyping for
      polymorphisms in the thymidylate synthase, cystathionine beta-synthase,
      methionine synthase, and methylenetetrahydrofolate reductase (MTHFR) genes was
      carried out using PCR and PCR-RFLP. RESULTS: Significantly higher levels of FH4
      were found in tumors from the proximal colon compared with those originating in
      the distal colon and rectum. Tumors with aberrant DNA methylation of CpG islands
      within promoter regions of the hMLH1, TIMP3, and ARF genes also contained higher
      levels of both 5,10-methylenetetrahydrofolate and FH4. In contrast, patients who
      were homozygous for the C667T polymorphism of the MTHFR gene had significantly
      lower concentrations of both these FIs in their tumor tissue. CONCLUSIONS: The
      concentrations of FIs in colorectal tumors are directly related to the presence
      of frequent DNA hypermethylation and inversely related to the presence of a
      common polymorphism in the MTHFR gene. FIs could serve as biochemical markers for
      the risk of developing this disease, as well as for the prediction of toxicity
      and efficacy of fluorouracil-based treatments.

PMID- 14676108
TI  - Neutrophils contribute to the biological antitumor activity of rituximab in a non
      Hodgkin's lymphoma severe combined immunodeficiency mouse model.
AB  - PURPOSE: Rituximab is a chimeric antibody (Ab) directed against the cluster
      designated (CD) 20 antigen found on normal and malignant B cells. Rituximab
      activity has been associated with complement-mediated cytotoxicity, Ab-dependent
      cellular cytotoxicity (ADCC), and induction of apoptosis. Recent studies
      performed in severe combined immunodeficiency (SCID) mouse models suggest that in
      vivo rituximab-associated ADCC is mediated via the FcgammaRIII receptor on
      effector cells. Despite low level expression of FcgammaRIII, neutrophils are also
      known to induce ADCC primarily via FcgammaRI receptor (CD64). The purpose of this
      work was to study the effect(s) of neutrophils on the in vivo antitumor activity
      of rituximab. EXPERIMENTAL DESIGN: To better characterize the biological activity
      of rituximab, we used a human non-Hodgkin's lymphoma animal model by injecting
      Raji cells i.v. into natural killer (NK) cell-depleted SCID mice. Disseminated
      disease involving liver, lung, and central nervous system developed, with
      subsequent death occurring approximately 3 weeks after tumor inoculation.
      Specifically, 6-8-week-old NK cell-depleted SCID mice were inoculated by tail
      vein injection with 1 x 10(6) Raji cells on day 0. The animals then were divided
      into three cohorts: (a) group A received placebo (PBS); (b) group B received
      rituximab administered via tail vein injection at 10 mg/kg on days 3, 5, 7, and
      11; and (c) group C consisted of neutrophil-depleted SCID mice treated with
      rituximab at 10 mg/kg on the same schedule. Neutrophils were depleted by i.p.
      administration of 80 microg of rat antimouse Ly-6G (Gr-1) Ab (BD PharMingen,
      Inc.) on days -1, 4, 9, and 14. The end point of the study was survival.
      Differences in outcome between treatment groups were analyzed by Kaplan-Meier
      methodology. RESULTS: Neutrophil- and NK cell-depleted SCID mice (group C) did
      not respond to rituximab, and the mean survival time was not significantly
      different from that of control mice. NK cell-depleted SCID mice with intact
      neutrophil function (group B) responded to rituximab, and 66% remained alive and
      appeared healthy after a mean follow-up period of 246 days. Overall, NK cell
      depleted SCID mice with intact neutrophil function treated with rituximab had
      statistically longer mean survival as compared with mice in neutrophil-depleted
      and control groups (161 days versus 28 days versus 22 days, P=0.003).
      CONCLUSIONS: In the absence of neutrophils, rituximab was less effective in
      controlling lymphoma cell growth or prolonging survival in our B-cell lymphoma
      SCID mouse model. Neutrophil-induced ADCC appears to contribute to the in vivo
      antitumor activity of rituximab. Strategies that improve the function of
      neutrophils, such as granulocyte-macrophage colony-stimulating factor or G-CSF
      priming, may increase the antitumor effects of rituximab. Additional in vivo
      animal studies are warranted.

PMID- 14676109
TI  - Sensitization to the cytotoxicity of cisplatin by transfection with nucleotide
      excision repair gene xeroderma pigmentosun group A antisense RNA in human lung
      adenocarcinoma cells.
AB  - PURPOSE: The resistance of tumor cells to chemotherapeutic agents, such as
      cisplatin, remains an important problem to be solved in cancer chemotherapy. One
      of the mechanisms associated with cisplatin resistance is the enhanced nucleotide
      excision repair (NER) capacity. Because xeroderma pigmentosum group A (XPA) plays
      a central role at an early stage in the NER pathway, we are interested in whether
      down-regulation of XPA gene expression by antisense RNA transfection could reduce
      DNA repair and thus sensitize tumor cells to cisplatin. EXPERIMENTAL DESIGN:
      Human lung adenocarcinoma cells were stably transfected XPA antisense RNA
      expression vector, and six colonies were selected for determining the XPA mRNA
      level by Northern blot. The cell viability was measured by an 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) metabolic assay, and
      the host cell reactivation was employed to assess the NER capacity of cisplatin
      damaged luciferase reporter plasmid. Flow cytometry analysis was used to
      determine cisplatin-induced apoptosis. RESULTS: We showed that transfection with
      antisense XPA RNA could decrease the XPA mRNA level and sensitize tumor cells to
      cisplatin. This enhanced sensitivity can be attributed to the reduced NER
      capacity in transfected cells as measured by the host cell reactivation assay.
      Moreover, the XPA mRNA level is correlated significantly with both cisplatin IC50
      value and cellular NER capacity. Furthermore, a more pronounced apoptotic
      response was observed in transfected cells treated by cisplatin. CONCLUSIONS: Our
      results suggest that the targeted inhibition of XPA by antisense strategy may
      provide a valuable tool in clinical cancer chemotherapy.

PMID- 14676110
TI  - Phase II study of imatinib in patients with small cell lung cancer.
AB  - PURPOSE: The purpose of our study was to assess the objective response to
      imatinib administered to patients with small cell lung cancer (SCLC).
      EXPERIMENTAL DESIGN: Eligible patients were those with SCLC who either had
      chemotherapy-naive extensive-stage or had SCLC in a sensitive relapse. Patients
      enrolled on the trial were treated with 600 mg of imatinib daily. The response
      was assessed using Southwest Oncology Group (SWOG) criteria after 3 and 6 weeks.
      Tumor specimens were examined by immunohistochemistry for the KIT receptor.
      RESULTS: Nineteen patients with SCLC entered on the study, including 16 men and 3
      women. Nine patients had previously untreated extensive-stage disease and 10
      patients had sensitive relapse. A central pathology review confirmed SCLC in only
      14 of the 19 patients. There were no objective responses; however, one patient
      with sensitive-relapse disease had prolonged stabilization of disease (>3 months)
      while on imatinib therapy. The median time to progression was 0.8 months (range,
      0.6-1.3 months) and 1.2 months (range, 0.2-4.1 months) in the previously
      untreated and sensitive-relapse groups, respectively. Tumor tissue samples from 4
      (21%) of the 19 patients had the KIT receptor (CD117). CONCLUSIONS: There was no
      observed antitumor activity in this limited Phase II trial of patients with SCLC,
      of which only a few tumors showed expression of the imatinib target. The results
      of this trial are, thus, inconclusive about the antitumor activity of imatinib
      against SCLC with the targeted KIT receptor (CD117). Further testing of imatinib
      in patients with SCLC will focus on demonstration of KIT expression in the
      setting of confirmed SCLC histology.

PMID- 14676111
TI  - Prognostic and therapeutic indicator of fluoroboronophenylalanine positron
      emission tomography in patients with gliomas.
AB  - PURPOSE: Boron neutron capture therapy (BNCT) for the treatment of brain tumors
      has attracted attention recently, and its clinical application has been
      progressing. We have focused on the use of BNCT with 10B-boronophenylalanine,
      which preferentially delivers boron-10 atoms to malignant cells through the amino
      acid transport system. In the present study, we evaluated the long-term outcomes
      of treatments using 18F-10B-fluoroboronophenylalanine (FBPA), which is an
      analogue of 10B-boronophenylalanine, by investigating the prognostic significance
      of the metabolic values and ratios of FBPA as determined by positron emission
      tomography (PET) in patients with gliomas. EXPERIMENTAL DESIGN: Our subjects were
      22 patients who underwent an FBPA-PET study and were followed for at least 4
      months thereafter. PET parameters, such as the rate constants K1, k2, k3, and k4,
      were measured before treatment. Data regarding the tumors, the contralateral
      normal region, and the uptake ratio of FBPA between the tumor and normal tissue
      40 min after injection of the tracer were compared with survival rates after the
      PET treatment. The survival time and the prognostic factors were tested using a
      Kaplan-Meier survival curve and Cox regression analysis, respectively. RESULTS:
      Among the clinical parameters, the histological grade of a tumor influences
      survival significantly. When the survival of patients with PET parameters or
      ratios above the median was compared with that of patients with parameters or
      ratios below the median, the most significant PET parameter was the K1 value of
      the tumor. Median survival in patients with a tumor K1 value of 0.033 ml/min
      (median value) or higher was 11 months, which was significantly shorter than the
      77 months in patients with a K1 value below the median (P=0.0006 by generalized
      Wilcoxon test). CONCLUSIONS: The kinetic constants of FBPA metabolism as
      determined by PET can be of ancillary significance in predicting the prognosis
      and indicating the feasibility of BNCT in patients with gliomas. The mean
      survival time was significantly shorter in patients with high uptakes of FBPA. A
      contributing factor is the K1 value, which reflects amino acid transport
      activity. FBPA-PET images can allow clinicians to develop treatment plans that
      are better tailored to the clinical features of their patients.

PMID- 14676112
TI  - Phase I trial of intraperitoneal docetaxel in the treatment of advanced
      malignancies primarily confined to the peritoneal cavity: dose-limiting toxicity
      and pharmacokinetics.
AB  - PURPOSE: The purpose of this Phase I study was to determine the maximum tolerated
      dose and dose-limiting toxicities (DLTs) of i.p. docetaxel and to determine the
      peritoneal pharmacokinetics and pharmacological advantage of this agent.
      EXPERIMENTAL DESIGN: Twenty-one patients with peritoneal carcinomatosis received
      docetaxel administered via an implanted i.p. catheter at doses of 40, 80, 100,
      125, or 156 mg/m2 every 3 weeks. DLTs on course 1 were used to define the maximum
      tolerated dose. RESULTS: Tumor types included gastric adenocarcinoma (n=7),
      ovarian cancer (n=4), other gastrointestinal primaries (n=3), and other cancers
      (n=7). Sixty cycles of i.p. docetaxel (median, 2; range, 1-11) were delivered.
      DLTs occurred in two patients at the 156 mg/m2 dose level; both developed an
      ileus, and one patient died of neutropenic sepsis. One of five evaluable patients
      treated with 125 mg/m2 docetaxel i.p. developed grade 4 neutropenic sepsis and
      stomatitis; another patient developed renal failure attributable to
      glomerulonephritis and grade 3 thrombocytopenia that was not judged to be dose
      limiting. One of six patients receiving 100 mg/m2 D, the recommended Phase II
      dose, developed grade 4 neutropenia lasting <5 days. Other non-DLT treatment
      related toxicities included dehydration requiring i.v. fluids, emesis,
      stomatitis, constipation, and abdominal pain. Best response on protocol therapy
      included 7 of 18 patients with stable disease for a median of 5 cycles (range, 2
      11); 11 patients progressed by the first evaluation after a median of 2 cycles
      (range, 1-3). There were three patients inevaluable for response who received
      only one cycle of i.p. docetaxel (two because of patient preference and one
      because of adhesion formation). Pharmacokinetic evaluation revealed mean plasma
      areas under the curves (AUC) at 100 and 125 mg/m2 i.p. docetaxel of 3.14 and 6.33
      microM.h (ranges, 1.02-5.88 and 3.97-12.70 microM. h), respectively; the mean
      peritoneal AUCs were 315 and 1063 microM.h (ranges, 250-373 and 239-2222
      microM.h), respectively. The mean peak plasma concentrations at 100 and 125 mg/m2
      i.p. docetaxel were 0.46 and 0.66 microM, and the mean peak peritoneal
      concentrations at those doses were 59 and 81 microM, respectively. The median and
      mean pharmacological advantage calculations (AUCperitoneal/AUCplasma) across all
      dose levels were 152 and 181, respectively (range, 18.8-367.4). The mean
      peritoneal 24- and 96-h concentrations were 0.9 microM (range, 0.2-1.6 microM)
      and <0.1 nM, respectively. The mean time that the concentration was >0.1 microM
      was 31.2 h (range, 27-36.5 h). CONCLUSIONS: i.p. docetaxel can be safely
      delivered at a dose of 100 mg/m2 i.p. every 3 weeks. This route of administration
      provides a significant peritoneal pharmacological advantage while delivering
      systemic concentrations consistent with the administration of standard i.v.
      doses.

PMID- 14676113
TI  - T-cell responses to HLA-A*0201 immunodominant peptides derived from alpha
      fetoprotein in patients with hepatocellular cancer.
AB  - PURPOSE: An existing immunological paradigm is that high concentrations of
      soluble protein contribute to the maintenance of peripheral tolerance/ignorance
      to self protein. We tested this hypothesis in a clinical immunotherapy trial
      using class I-restricted peptide epitopes derived from alpha-fetoprotein (AFP).
      AFP is a self protein expressed by fetal liver at high levels, but
      transcriptionally repressed at birth. AFP is de-repressed in a majority of
      hepatocellular carcinomas (HCCs) and patients with active disease can have plasma
      levels in the mg/ml range. We previously identified four immunodominant HLA
      A*0201-restricted peptides derived from human AFP that could stimulate specific T
      cell responses in normal volunteer peripheral blood lymphocytes cultures. We
      wished to test the hypothesis that AFP peptide-reactive T cells could be expanded
      in vivo in HCC patients immunized with these four AFP peptides. EXPERIMENTAL
      DESIGN: We undertook a pilot Phase I clinical trial in which HLA-A*0201 patients
      with AFP-positive HCC were immunized with three biweekly intradermal vaccinations
      of the four AFP peptides (100 microg or 500 microg each) emulsified in incomplete
      Freund's adjuvant. RESULTS: All of the patients (n=6) generated T-cell responses
      to most or all of the peptides as measured by direct IFNgamma enzyme-linked
      immunospot (ELISPOT) and MHC class I tetramer assays. CONCLUSIONS: We conclude
      that the human T-cell repertoire is capable of recognizing AFP in the context of
      MHC class I even in an environment of high circulating levels of this oncofetal
      protein.

PMID- 14676114
TI  - A Phase II study of weekly irinotecan and capecitabine in patients with
      previously treated non-small cell lung cancer.
AB  - PURPOSE: Irinotecan and capecitabine have synergistic antitumor activity with
      distinct mechanisms of action but without overlapping major toxicity. We
      conducted a Phase II study to evaluate the efficacy of weekly irinotecan plus
      capecitabine in patients with previously treated non-small cell lung cancer
      (NSCLC). EXPERIMENTAL DESIGN: Eligible patients had received at least one prior
      chemotherapy regimen. The treatment consisted of irinotecan (90-100 mg/m2 i.v.)
      on days 1 and 8 plus capecitabine (1000 mg/m2 p.o. b.i.d.) on days 1-14 of a 21
      day cycle. Treatment was given until disease progression or unacceptable
      toxicity. RESULTS: Thirty-seven patients with median age of 59 years were
      enrolled. Eighteen (49%) patients had received one prior regimen, and 19 (51%)
      patients had received two or more prior regimens. The Initial 5 patients received
      100 mg/m2 irinotecan with grade 3 diarrhea seen in 3 of 5 patients, and
      subsequent 32 patients received 90 mg/m2 irinotecan. Four (11.4%) of 35 evaluable
      patients had partial response and 12 (34.3%) had stable disease. There was no
      complete response. All responses were noted in patients who had received one
      prior regimen (4 of 18, 22%), but there was no response among the patients who
      had received two or more regimens. Median duration of response was 5.6 months
      (range, 5-8.7 months). At a median follow-up of 6 months, median survival was 7.4
      months (95% confidence interval, 3.6-9.0). Grade 3 or 4 toxicities were
      neutropenia (12%), anemia (13%), and diarrhea (12%) at the dose level of 90
      mg/m2. CONCLUSIONS: Weekly irinotecan plus capecitabine had favorable antitumor
      activity and toxicity profile as a second-line treatment for recurrent NSCLC.
      This regimen may provide an additional treatment option for patients with
      advanced NSCLC.

PMID- 14676115
TI  - Prospective study of the airways and pulmonary parenchyma of patients at risk for
      a second lung cancer.
AB  - PURPOSE: We conducted our study to compare the number of preneoplastic lesions in
      the airways and nodules in the pulmonary parenchyma of patients with resected non
      small cell lung cancer with the patients whose treatment included chest
      radiotherapy. EXPERIMENTAL DESIGN: Patients were eligible if they had
      successfully resected stage I and II non-small cell lung cancer or advanced stage
      non-small cell or small cell lung cancer treated with chest radiotherapy with or
      without chemotherapy and were free of cancer for >2 years. Patients underwent a
      history and physical examination, white light and fluorescence bronchoscopy, and
      computerized tomography of the chest. The airway epithelium was examined for
      preneoplastic histological changes, and the pulmonary parenchyma was examined for
      the presence of nodules. RESULTS: Twenty-nine patients at risk for lung cancer
      were studied between 1997 and 1999. Two patients treated with chest radiotherapy
      had an area of moderate dysplasia (n=1) and carcinoma in situ (n=1), whereas one
      patient treated with surgical resection alone had an area of mild dysplasia. Six
      other patients had metaplasia detected in their airway epithelium. Ten of the 13
      patients treated with chest radiotherapy had pulmonary nodules compared with 5 of
      the 13 patients treated with surgical resection alone. CONCLUSIONS: Mild
      dysplasia, moderate dysplasia, severe dysplasia, and carcinoma in situ are
      unusual in patients with resected lung cancer who have stopped smoking for an
      extended period of time. Patients with lung cancer treated with chest irradiation
      may be at higher risk for preneoplastic lesions and pulmonary nodules than
      patients treated with surgical resection alone, but additional patients will need
      to be studied.

PMID- 14676116
TI  - A Phase II study of the polyamine analog N1,N11-diethylnorspermine (DENSpm) daily
      for five days every 21 days in patients with previously treated metastatic breast
      cancer.
AB  - PURPOSE: Polyamines are ubiquitous intracellular polycationic molecules essential
      for cell growth and differentiation. Polyamine analogs down-regulate ornithine
      decarboxylase, induce spermidine/spermine N1-acetyltransferase, deplete natural
      polyamine pools, inhibit growth, and induce programmed cell death in breast
      cancer models. This study evaluated the activity of the first-generation analog
      DENSpm in women with metastatic breast cancer. EXPERIMENTAL DESIGN: The overall
      accrual goal was 34 patients (30 evaluable) in a two-stage design. The second
      stage of accrual was to proceed if > or =2 among first 15 evaluable patients were
      progression free at 4 months. The primary objective was to determine whether > or
      =20% of metastatic breast cancer patients treated with DENSpm as second- or third
      line therapy remained progression free after 4 months. RESULTS: Sixteen patients
      (median age, 52 years; range, 34-65; median performance status, 1; range, 0-1)
      enrolled in the first stage received 43 cycles (median, 2; range, 1-6) of 100
      mg/m2 DENSpm as a 15-min infusion i.v. on days 1-5 every 21 days. All 16 patients
      were evaluable for toxicity; 15 were evaluable for response. All patients had
      disease progression by 4 months, and the study closed after the first stage of
      accrual. The main toxicities included grade 1-2 abdominal pain, transient
      perioral numbness, nausea, and grade 1 thrombocytopenia. Two patients had grade 3
      abdominal pain during cycle 2 infusion: one was hospitalized, and another was
      subsequently retreated at 80% dose without pain recurrence. CONCLUSIONS: Although
      this dose and administration schedule of DENSpm was quite tolerable, no evidence
      of clinical activity was detected. Encouraging preclinical activity of polyamine
      analogs alone and in combination with cytotoxic drugs supports the continued
      evaluation of newer-generation polyamine analogs for the treatment and prevention
      of breast cancer.

PMID- 14676117
TI  - Phase I and correlative study of combination bryostatin 1 and vincristine in
      relapsed B-cell malignancies.
AB  - PURPOSE: Bryostatin 1 activates protein kinase C (PKC) with short-term exposure
      and results in depletion of PKC with prolonged exposure. Preclinical in vitro and
      in vivo studies demonstrate synergistic activity and increased tumor apoptosis in
      B-cell malignancies when a prolonged infusion of bryostatin 1 is followed by
      vincristine. EXPERIMENTAL DESIGN: We embarked on a Phase I trial of bryostatin 1
      as a 24-h continuous infusion followed by bolus vincristine in patients with
      refractory B-cell malignancies other than acute leukemias. Twenty-four evaluable
      patients were enrolled. RESULTS: The dose-limiting toxicity was myalgia. The MTD
      and recommended Phase II dose of bryostatin 1 was 50 microg/m2/24 h followed by
      vincristine 1.4 mg/m2 (maximum total dose of 2 mg) repeated every 2 weeks.
      Significant antitumor activity was observed in this relapsed population,
      including patients who had failed high-dose chemotherapy. This included 5 durable
      complete and partial responses and 5 patients with stable disease lasting > or =6
      months (range, 6-48+ months). Median time to response was 8 months. Correlative
      studies demonstrated a progressive increase in serum interleukin-6 with
      bryostatin 1 infusion followed by an additional increase after vincristine. Flow
      cytometry for detection of apoptosis in B and T cells showed an initial decrease
      in apoptotic frequency in CD5+ cells within 6 h of bryostatin 1 infusion
      compatible with its known increase in PKC activity in the majority of patients
      followed by a return to baseline or overall increase in apoptotic frequency after
      completion of infusion. All (5 of 5) patients who had an overall increase in
      apoptotic frequency in CD5+ cells achieved either a clinical response or
      prolonged stable disease. Four of these 5 patients did not have the initial
      decrement in apoptosis at 6 h. CONCLUSIONS: Given the lack of myelosuppression
      and early evidence of clinical efficacy, additional exploration of this regimen
      in non-Hodgkin's lymphoma and multiple myeloma is warranted.

PMID- 14676118
TI  - Induction chemotherapy followed by concomitant TFHX chemoradiotherapy with
      reduced dose radiation in advanced head and neck cancer.
AB  - PURPOSE: Induction chemotherapy with carboplatin and paclitaxel followed by
      concomitant TFHX (paclitaxel, infusional 5-fluorouracil, hydroxyurea, and twice
      daily radiation therapy administered every other week) has resulted in 70% 3-year
      survival in stage IV patients. Locoregional and distant control rates were 94 and
      93%, respectively. In an attempt to decrease toxicity without compromising local
      control, a second cohort of patients was treated with a lower dose of radiation
      to sites of potential microscopic disease. EXPERIMENTAL DESIGN: Sixty-four
      patients were entered on study. Patients received six weekly doses of carboplatin
      (area under the curve 2) and paclitaxel (135 mg/m2) followed by five cycles of
      TFHX. The radiation dose to gross disease was 75 Gy as in the previous trial. The
      radiation dose to high-risk microscopic disease was reduced from 60 to 54 Gy, and
      the dose to low-risk microscopic disease was reduced from 45 to 39 Gy. RESULTS:
      Ninety-seven percent of patients had stage IV disease. The response rate to
      induction chemotherapy was 82% with a complete response rate of 42%. At the
      completion of therapy the clinical complete response rate rose to 100% with a
      median follow-up of 29 months. The actuarial 2 and 3-year survival was 77 and
      70%, respectively. Five patients developed progressive disease for an overall 3
      year progression-free survival of 90%. Two patients failed in locoregional sites
      alone, resulting in a 3-year locoregional control of 97%. The 3-year systemic
      control was 95%. Four patients were completely feeding tube dependent at the time
      of analysis. Only 1 of these patients had normal swallowing function before
      treatment. CONCLUSIONS: In this second trial, induction chemotherapy with
      carboplatin and paclitaxel followed by TFHX chemoradiotherapy results in high
      survival and progression-free survival. The reduction in radiation dose did not
      compromise survival or disease control compared with our prior study using higher
      radiation doses. Data continues to support definitive evaluation of this
      approach.

PMID- 14676119
TI  - Pilot trial of trastuzumab starting with or after the doxorubicin component of a
      doxorubicin plus paclitaxel regimen for women with HER2-positive advanced breast
      cancer.
AB  - PURPOSE: Combining trastuzumab with doxorubicin and paclitaxel (AT) is attractive
      because of the activity of AT and survival improvements observed when trastuzumab
      is added to either agent in HER2-positive metastatic breast cancer. This pilot
      study evaluates the efficacy and cardiac tolerability of AT followed by
      paclitaxel with trastuzumab started with AT or paclitaxel alone and investigates
      pharmacokinetic interactions. EXPERIMENTAL DESIGN: Two cohorts of 16 patients
      were enrolled. Cohort 1 received three cycles of AT (60/150 mg/m2) plus
      trastuzumab (4 mg/kg initial dose followed by 2 mg/kg), initiated concomitantly
      with doxorubicin, followed by nine cycles of paclitaxel (80 mg/m2) plus
      trastuzumab and then trastuzumab alone. Cohort 2 was treated with the same
      regimen, but trastuzumab was initiated with paclitaxel after AT. Cardiac
      function, pharmacokinetic interactions, and efficacy were evaluated. RESULTS:
      Median baseline left ventricular ejection fraction (LVEF) was 62% (range, 57-74%)
      and 66% (range, 57-77%) in cohorts 1 and 2, respectively. Most patients had an
      absolute decrease in LVEF. Congestive heart failure was not observed. LVEF in
      three patients decreased to <50% but recovered despite continued treatment.
      Response rates were 87.5% in both cohorts (cohort 1:2 complete response, 12
      partial response; cohort 2:3 complete response, 11 partial response). No
      unexpected side effects were observed. Pharmacokinetics of paclitaxel and its
      metabolites and of doxorubicin were similar without and with trastuzumab.
      CONCLUSIONS: Trastuzumab administered with AT followed by weekly paclitaxel alone
      is highly active whether trastuzumab is initiated with AT or paclitaxel.
      Congestive heart failure was not observed, and LVEF decreases were reversible.
      Further studies of this regimen are warranted.

PMID- 14676120
TI  - Altered subcellular localization and low frequency of mutations of ING1 in human
      brain tumors.
AB  - PURPOSE: Clinical and experimental evidence suggest that the p33ING1b candidate
      tumor suppressor functionally cooperates with p53 in controlling biochemical and
      biological functions. Because p53 is frequently mutated in brain tumors and the
      ING1 locus maps to a site of which the loss is associated with gliomas, we
      analyzed the mutation and expression profiles of ING1B in human brain tumors.
      Here we present the first report of ING1 expression and mutation analyses in
      human brain tumor samples and malignant glioma cell lines. EXPERIMENTAL DESIGN:
      Expression and mutation analyses of ING1B together with subcellular localization
      studies of ING1 proteins were performed on 29 brain tumor specimens and 6 human
      glioma cell lines. RESULTS: A single point mutation (3.5%) was detected in the 29
      brain tumor specimens analyzed. This missense mutation occurred in a sequence
      reported previously to confer nuclear translocation properties to p33ING1b.
      Interestingly, overexpression and subcellular mislocalization of p33ING1b were
      observed in all 29 of the brain tumor specimens and some glioma cell lines. In
      tumor samples, ING1 proteins aberrantly localized to the cytoplasm, and to a
      lesser extent, to the nucleus of glioma cells. CONCLUSIONS: Our data indicate
      that although mutations of ING1 seem to be infrequent in human brain tumors,
      deregulated expression and mislocalization of ING1 proteins, particularly the
      p33ING1b isoform, are common events in gliomas and glioblastomas.

PMID- 14676121
TI  - Vascular endothelial growth factor C mRNA expression correlates with stage of
      progression in patients with melanoma.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF)-C promotes the ingrowth and
      invasion of lymphatics in many different tumor types, including melanoma. To
      determine whether expression of VEGF-C correlates with stage of progression, we
      measured VEGF-C mRNA levels in melanomas representing different stages of
      progression and from the vertical and horizontal growth-phase of individual
      primary melanomas. EXPERIMENTAL DESIGN: Total RNA was extracted from human
      melanoma specimens taken from operative specimens and subjected to quantitative
      real-time PCR. VEGF-C levels were determined for 54 melanoma samples, including
      primary melanomas (n=15), local recurrences (n=6), regional dermal metastases
      (n=11), nodal metastases (n=12), and distant metastases (n=10). As a surrogate
      for lymphatic density, we also measured the expression of the lymphatic
      endothelial marker LYVE-1 and correlated its expression with previously measured
      VEGF-C levels. RESULTS: Vertical growth phase melanomas expressed significantly
      higher levels of VEGF-C than horizontal growth phase melanomas. Nodal metastases
      expressed the highest level of VEGF-C, followed by regional dermal metastases.
      Primary and local recurrences expressed a relatively low level of VEGF-C, as did
      negative lymph nodes and distant metastases. In addition, VEGF-C expression
      correlated well with LYVE-1 expression (r=0.611; P<0.0001). CONCLUSIONS: These
      data suggest that high levels of VEGF-C may be important in regional lymphatic
      disease in melanoma and that VEGF-C and LYVE-1 levels may identify tumors with a
      high risk for nodal metastases, for which antilymphangiogenic therapy may be more
      effective.

PMID- 14676122
TI  - Inverse correlation between heparan sulfate composition and heparanase-1 gene
      expression in thyroid papillary carcinomas: a potential role in tumor metastasis.
AB  - PURPOSE: Heparanase-1 (HPR1) is an endoglycosidase that degrades the side chains
      of heparan sulfate proteoglycan (HSPG), a key component in cell surfaces, the
      extracellular matrix (ECM), and the basement membrane (BM). The purpose of this
      study was to evaluate HPR1 expression in thyroid neoplasms and its effect in
      degrading the HSPG substrates in the ECM and BM and to determine its role in
      thyroid tumor metastasis. EXPERIMENTAL DESIGN: HPR1 mRNA expression was analyzed
      by using in situ hybridization with a digoxigenin-labeled antisense RNA probe on
      paraffin-embedded tumor sections and reverse transcription-PCR (RT-PCR) in fresh
      tumor tissues. HPR1 protein expression was analyzed by using immunohistochemical
      staining with an anti-HPR1 rabbit antiserum and immunofluorescence (IF) with an
      anti-HPR1 monoclonal antibody. The effect of HPR1 expression in thyroid neoplasms
      was analyzed by examining the presence and integrity of the HSPG substrates in
      the ECM and BM using IF staining with a specific monoclonal antibody against
      heparan sulfate. The relationship of HPR1 expression in papillary thyroid
      carcinomas (PTCs) with various clinicopathological parameters was analyzed
      statistically. The role of HPR1 in thyroid tumor metastasis was further examined
      by comparing HPR1 levels in 10 thyroid tumor cell lines to their invasive and
      metastatic potential. RESULTS: In situ hybridization analysis of 81 tumor samples
      (62 papillary carcinomas and 19 follicular adenomas) revealed that HPR1 was
      expressed at a much higher frequency in PTCs than in follicular adenomas
      (P<0.05). RT-PCR analyses of fresh tumor tissues revealed that HPR1 mRNA could be
      detected in primary and metastatic thyroid papillary carcinomas. HPR1 expression
      was confirmed at the protein level by immunohistochemical staining and IF
      stainings. IF analysis of HSPG revealed that HS was deposited abundantly in the
      BM of normal thyroid follicles and benign follicular adenomas but was absent in
      most thyroid papillary carcinomas. A lack of heparan sulfate in PTCs inversely
      correlated with HPR1 expression. Clinicopathological data analyses revealed that
      PTCs with local and distant metastases scored HPR1 positive at a significantly
      higher frequency than nonmetastatic thyroid cancers (P=0.02). To further explore
      the role of HPR1 in tumor metastases, we characterized HPR1 expression in 10
      thyroid tumor cell lines using RT-PCR and Western blot and measured HPR1
      enzymatic activity using a novel ELISA. HPR1 was differentially expressed in
      different types of cell lines; overexpression of HPR1 in two tumor cell lines led
      to a dramatic increase of their invasive potential in vitro in an artificial BM.
      CONCLUSIONS: Our study suggests that HPR1 expressed in papillary carcinomas is
      functional and that HPR1 expression is associated with thyroid tumor malignancy
      and may significantly contribute to thyroid tumor metastases.

PMID- 14676123
TI  - Feasibility of using low-volume tissue samples for gene expression profiling of
      advanced non-small cell lung cancers.
AB  - PURPOSE: The majority of patients with non-small cell lung cancer (NSCLC) present
      at an advanced clinical stage, when surgery is not a recommended therapeutic
      option. In such cases, tissues for molecular research are usually limited to the
      low-volume samples obtained at the time of diagnosis, usually via fine-needle
      aspiration (FNA). We tested the feasibility of performing gene expression
      profiling of advanced NSCLCs using amplified RNA from lung FNAs. EXPERIMENTAL
      DESIGN AND RESULTS: A total of 46 FNAs was tested, of which 18 yielded RNA of
      sufficient quality for microarray analysis. Expression profiles of these 18
      samples were compared with profiles of 17 pairs of tumor and normal lung tissues
      that had been surgically obtained. Using a variety of unsupervised and supervised
      analytical approaches, we found that the FNA profiles were highly distinct from
      the normal samples and similar to the tumor profiles. CONCLUSIONS: We conclude
      that when RNA amplification is successful, gene expression profiles from NSCLC
      FNAs can determine malignancy and suggest that with additional refinement and
      standardization of sample collection and RNA amplification protocols, it will be
      possible to conduct additional and more detailed molecular analysis of advanced
      NSCLC using lung FNAs.

PMID- 14676124
TI  - Global expression analysis of well-differentiated pancreatic endocrine neoplasms
      using oligonucleotide microarrays.
AB  - PURPOSE: Pancreatic endocrine neoplasms (PENs) are rare, mostly well
      differentiated endocrine neoplasms, whose biology has been poorly characterized.
      Global expression microarrays can document abnormal pathways that impact on
      tumorigenesis and disease progression. EXPERIMENTAL DESIGN: RNA was extracted
      from eight well-differentiated PENs and three highly enriched pancreatic islet
      cell samples (80-90% purity), and examined using the Affymetrix U133A
      oligonucleotide microarray. Microarray data were normalized using dCHIP for
      identification of differentially expressed genes. PEN tissue microarrays were
      constructed from 53 archival PENs for immunohistochemical validation of
      microarray data. RESULTS: Sixty-six transcripts were overexpressed > or =3-fold
      in PENs compared with normal islet cells, including putative oncogenes
      (MLLT10/AF10), growth factors [insulin-like growth factor-binding protein 3
      (IGFBP3)], cell adhesion and migration molecules (fibronectin), and endothelial
      elements (MUC18/MelCAM and CD31). A total of 119 transcripts were underexpressed
      < or =3-fold in PENs compared with normal islet cells, including cell cycle
      checkpoint proteins (p21/Cip1), the MIC2 (CD99) cell surface glycoprotein,
      putative metastasis suppressor genes (NME3), and junD, a MEN1-regulated
      transcription factor. Using PEN tissue microarrays, we confirmed the differential
      up-regulation of IGFBP3 (70%) and fibronectin (22%) and differential down
      regulation of p21 (46%) and MIC2 (CD99; 91%) in PENs versus normal pancreatic
      islets. IGFBP3 overexpression was significantly more common in metastatic (93%)
      versus primary PEN lesions (60%), P=0.022. Fibronectin overexpression
      demonstrated a trend toward significance in lymphatic PEN metastases (55%)
      compared with primary PEN lesions (24%; P=0.14). CONCLUSIONS: Global expression
      analysis provides insight into tumorigenic pathways in PENs and may identify
      potential prognostic and therapeutic markers for these uncommon neoplasms.

PMID- 14676125
TI  - Interleukin-8 serum levels in patients with hepatocellular carcinoma:
      correlations with clinicopathological features and prognosis.
AB  - PURPOSE: In this study, we measured the serum interleukin-8 (IL-8) levels in
      patients with hepatocellular carcinoma (HCC) to evaluate its correlation with
      clinicopathological features and prognosis. EXPERIMENTAL DESIGN: ELISA was used
      to detect the concentrations of IL-8, vascular endothelial growth factor, and
      macrophage migration inhibitory factor in preoperative sera of 59 patients with
      resection of HCC and 15 healthy subjects. RESULTS: Preoperative serum IL-8 was
      found to be significantly elevated in patients with HCC compared with healthy
      subjects (median, 17.6 versus 1.0 pg/ml, P=0.046). The levels of IL-8 correlated
      significantly with a large tumor size (>5 cm), absence of tumor capsule, presence
      of venous invasion, and advanced pathological tumor-node-metastasis stage. Serum
      IL-8 level was a significant prognostic factor in terms of disease-free and
      overall survival. Patients with a serum IL-8 level of >17.6 pg/ml had a poorer
      disease-free survival than those with a level of <17.6 pg/ml (median disease-free
      survival 4.7 versus 19.2 months). Multivariate analyses showed that serum IL-8
      level was a significant and independent prognostic factor of survival.
      CONCLUSIONS: Significant correlations of serum IL-8 levels with tumor size and
      tumor stage suggest that IL-8 may be directly or indirectly involved in the
      progression of HCC. These findings indicate that serum IL-8 may be a useful
      biological marker of tumor invasiveness and an independent prognostic factor for
      patients with HCC.

PMID- 14676126
TI  - Phase I and II carcinogen metabolism gene expression in human lung tissue and
      tumors.
AB  - PURPOSE: The regulation of carcinogen metabolism machinery may involve proximate
      tobacco smoke exposure, hormonal and other endogenous coregulatory factors, and
      an individual's underlying genetic responsiveness. The mRNA and protein
      expression patterns of known carcinogen metabolism genes encoding the aromatic
      hydrocarbon receptor Ahr; the cytochromes P450 CYP1A1 and CYP1B1; glutathione S
      transferases GSTM1, GSTM3, GSTP1, and GSTT1; and NADPH quinone oxidoreductase
      NQO1 were examined. EXPERIMENTAL DESIGN: Paired tumor and nontumor lung tissue
      from 45 subjects was subject to a recently devised RNA-specific qualitative
      reverse transcription-PCR strategy, as well as Western immunoblotting. Tobacco
      exposure measured by plasma biomarkers nicotine and cotinine, plasma estradiol
      levels, alpha and beta estrogen receptor (ER) expression in the lung, gender,
      age, and histological diagnosis were then analyzed using multivariate regression
      models. RESULTS: In nontumor lung tissue, multivariate models identified several
      correlates of mRNA expression: (a) CYP1B1 in females (positively: smoke status,
      P=0.024; ER-beta expression, P=0.024); (b) GSTT1 in females (positively:
      cotinine, P=0.007; negatively: age, P=0.001; ER-beta expression, P=0.005) and in
      males (positively: plasma estradiol, P=0.015; ER-beta expression, P=0.025); and
      (c) NQO1 in females (positively: smoke status, P=0.002) and in males (positively:
      ER-beta expression, P=0.001). CYP1A1 (mRNA, 9.1%) and GSTM1 (mRNA, 17.5%) are
      uncommonly expressed in human lung. Confirmation by Western immunoassayed protein
      is described. The results in nontumor tissue differed from that in tumor tissue.
      CONCLUSIONS: Regulation of carcinogen metabolism genes expressed in human lung
      seems impacted by hormonal and gender factors, as well as ongoing tobacco
      exposure. Expression differences between tumor and nontumor tissue in this
      pathway have both susceptibility and therapeutic implications.

PMID- 14676127
TI  - Altered gene expression of folate enzymes in adjacent mucosa is associated with
      outcome of colorectal cancer patients.
AB  - PURPOSE: The purpose of this study was to analyze whether gene expression levels
      of folate enzymes in adjacent mucosa were associated with outcome of colorectal
      cancer patients. EXPERIMENTAL DESIGN: Real-time PCR was used to quantify
      expression levels of folate-associated genes including the reduced folate carrier
      (RFC-1), folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH),and
      thymidylate synthase (TS) in tumor tissue and adjacent mucosa of patients with
      primary colorectal cancer (n=102). Furthermore, reduced folates in the tissues
      were measured with a binding-assay method. RESULTS: Mean gene expression levels
      of RFC-1, FPGS, GGH, and TS were significantly higher in tumor biopsies compared
      with mucosa. Univariate and multivariate analyses showed that the FPGS gene
      expression level in mucosa, but not in tumor, was a prognostic parameter
      independent of the clinicopathological factors with regard to survival. Patients
      with high FPGS levels (>0.92) in mucosa also showed significantly higher total
      folate concentrations (P=0.03) and gene expression levels of RFC-1 (P<0.01), GGH
      (P<0.01), and TS (P=0.04) compared with patients with low FPGS levels. The total
      reduced folate concentration correlated with the gene expression levels of RFC-1
      and FPGS but not with TS or GGH. CONCLUSION: Our results suggest that normal
      appearing colonic mucosa adjacent to primary colon cancer can show altered gene
      expression levels of FPGS that may have bearing on the development of aggressive
      metastatic behavior of the tumor and on tumor-specific survival.

PMID- 14676128
TI  - Inhibition of Kaposi's sarcoma in vivo by fenretinide.
AB  - PURPOSE: We examined the effects of fenretinide [N-(4-hydroxyphenyl)retinamide;
      (4HPR)] on highly angiogenic Kaposi's sarcoma tumors in vivo and investigated the
      mechanisms involved for potential clinical applications. EXPERIMENTAL DESIGN: (CD
      1)BR nude mice bearing KS-Imm cell tumors were randomized to receive 4HPR or
      vehicle until sacrifice. In vitro, KS-Imm and endothelial cells were treated with
      4HPR to study the effects on proliferation, apoptosis, migration, and invasion;
      in vivo angiogenesis was evaluated in the Matrigel model. Angiogenesis-related
      and retinoid receptor molecules were examined at the mRNA and protein expression
      levels. RESULTS: In vivo, 4HPR significantly (P<0.001) reduced growth of
      detectable Kaposi's sarcoma (KS) xenografts and inhibited angiogenesis in the
      Matrigel plug assay (P<0.04). In vitro, 4HPR affected KS-Imm and endothelial cell
      growth and KS-Imm migration and invasion. 4HPR invasion inhibition was associated
      with decreased release of matrix metalloprotease-2 and rapid reduction of
      vascular endothelial growth factor (VEGF) expression by KS cells and of vascular
      endothelial growth factor receptor 2 (VEGFR2) by KS and endothelial cells.
      Finally, 4HPR repression of angiogenesis was associated with a 4HPR-induced
      increase in retinoic acid receptor beta expression. CONCLUSIONS: These data
      indicate that 4HPR inhibits KS tumor growth in vivo through a mechanism involving
      the modulation of angiogenesis-associated growth factors and their receptors on
      both tumor and endothelial cells. In addition, 4HPR inhibited invasion by
      decreasing of matrix metalloprotease-2 activity. Our results justify further
      studies to evaluate the utility of 4HPR as a chemopreventive or therapeutic agent
      in KS, a malignancy associated with immune suppression that has a high risk of
      recurrence with highly active antiretroviral therapy failure.

PMID- 14676129
TI  - Capecitabine inhibits postoperative recurrence and metastasis after liver cancer
      resection in nude mice with relation to the expression of platelet-derived
      endothelial cell growth factor.
AB  - PURPOSE: This study was to investigate the effect of capecitabine on recurrent
      tumor and metastasis after curative resection of liver cancer, xenograft of a
      highly metastatic human hepatocellular carcinoma (HCC) tumor (LCI-D20), with
      special reference to the expression of platelet-derived endothelial cell growth
      factor (PD-ECGF). EXPERIMENTAL DESIGN: LCI-D20 and LCI-D35 (a low metastatic
      human HCC model) liver tumors were orthotopically implanted in 96 nude mice and
      divided into a treatment group (24 LCI-D20 mice and 24 LCI-D35 mice) and a
      prevention group (48 LCI-D20 mice). In the prevention group, curative resection
      of liver tumors was done 10 days after the orthotopic implantation of LCI-D20
      tumor. Arabic gum (control), 5-fluorouracil (5-FU), and capecitabine were
      administrated respectively to all of the 96 mice. RESULTS: In the treatment
      group, tumor volume was 468 +/- 138, 442 +/- 81, and 240 +/- 119 mm3 (P<0.01) in
      the control, 5-FU, and capecitabine subgroups, respectively, in LCI-D20 mice,
      whereas it was 168 +/- 35, 164 +/- 23, and 144 +/- 21 mm3 (P>0.05), respectively,
      in LCI-D35 mice. In the prevention group, incidence of liver recurrence in the
      control, 5-FU, and capecitabine subgroups was 100, 100, and 50%; lung metastasis
      being 100, 100, and 17%; and life span being 31 +/- 5, 37 +/- 5, and 77 +/- 19
      days, respectively. PD-ECGF was highly expressed in HCC and its metastatic
      tissues in LCI-D20 mice and hardly expressed in HCC tissues in LCI-D35 mice.
      CONCLUSIONS: Capecitabine inhibits tumor growth and metastatic recurrence after
      resection of HCC in highly metastatic nude mice model. The effect of capecitabine
      may be attributed to the high expression of PD-ECGF in tumors.

PMID- 14676130
TI  - Combination of interferon-beta and the angiotensin-converting enzyme inhibitor,
      perindopril, attenuates murine hepatocellular carcinoma development and
      angiogenesis.
AB  - PURPOSE: Angiogenesis is now recognized as a crucial step in the development of
      tumors, including hepatocellular carcinoma (HCC). The aim of this study was to
      elucidate the combined effect of the clinically used angiotensin I-converting
      enzyme (ACE) inhibitor, perindopril (PE), and IFN-beta on the development and
      angiogenesis of murine HCC at clinically comparable low doses. EXPERIMENTAL
      DESIGN: PE and IFN were administered at doses of 2 mg/kg/day and 1 x 10(4)
      IU/twice a week, respectively. RESULTS: Both PE and IFN significantly suppressed
      HCC development and inhibited neovascularization in the tumor, although the
      effect of low-dose IFN was weaker than that of PE. A combination regimen of PE
      plus IFN was effective; IFN significantly augmented the tumoricidal effect of PE.
      These inhibitory effects of PE plus IFN could be detected even on established
      tumors. The potent angiogenic factor, vascular endothelial growth factor, was
      markedly suppressed by combined treatment with PE and IFN, whereas these agents
      produced a marked increase of apoptosis in the tumor. The in vitro studies
      exhibited that PE and IFN inhibited endothelial cell tubular formation. IFN also
      suppressed endothelial cell proliferation, whereas neither IFN nor PE showed any
      inhibitory effect on proliferation of HCC cells. CONCLUSION: The combination
      treatment of PE and IFN at clinically comparable low doses could inhibit HCC
      development and angiogenesis and suppress vascular endothelial growth factor as
      well. Because both agents are widely used in clinical practice, this combination
      regimen may represent a potential new strategy for HCC therapy in the future.

PMID- 14676131
TI  - Decreased expression of bone morphogenetic protein (BMP) receptor type II
      correlates with insensitivity to BMP-6 in human renal cell carcinoma cells.
AB  - PURPOSE: Bone morphogenetic proteins (BMPs) are members of a family of
      pleiotropic growth factors that play a critical role during renal development as
      well as maintaining kidney homeostasis. In the present study, we investigated the
      potential role of BMP receptors (BMPRs) in renal cell carcinoma (RCC) cells.
      EXPERIMENTAL DESIGN: Immunohistochemistry was used to investigate the expression
      of BMPRs in human RCC tissues. As an in vitro model of RCC, three cell lines were
      used: 112, 117, and 181. Northern blot, immunoblot, and reverse transcription-PCR
      were used to study the expression of BMPRs in the cell lines. Finally, cells were
      transfected using LipofectAMINE. RESULTS: Normal human kidney tissues express the
      three BMPRs: types RIA, RIB, and RII. In contrast, human RCC cells frequently
      exhibit a loss of expression of BMP-RII. In tissue culture, BMP-6 inhibits in a
      dose-dependent manner the proliferation of 112 cells but not of 117 and 181
      cells. Assays for BMPRs demonstrated that 117 and 181 cells express low levels of
      BMP-RII RNA. When these two BMP-6 resistant cell lines were infected with the
      adenovirus containing the constitutively active form of BMP-RIA or -RIB in
      combination with a BMP-6-responsive luciferase reporter construct, luciferase
      activity increased. Finally, when these cell lines were transfected with BMP-RII,
      BMP-6-sensitivity was restored. CONCLUSIONS: These results demonstrate that human
      RCC tissues frequently have decreased levels of expression of BMP-RII and that
      the human RCC cell lines 117 and 181 are resistant to the growth-inhibitory
      effect of BMP-6 because they have decreased levels of expression of BMP-RII.

PMID- 14676132
TI  - The cyclin-dependent kinase inhibitor flavopiridol potentiates gamma-irradiation
      induced apoptosis in colon and gastric cancer cells.
AB  - PURPOSE: Flavopiridol is a cyclin-dependent kinase inhibitor currently under
      development by the National Cancer Institute both as a single agent and in
      combination with chemotherapy. There have been numerous reports that flavopiridol
      potently enhances the induction of apoptosis by chemotherapy. However, the effect
      of flavopiridol on radiotherapy (RT)-induced apoptosis has been largely untested.
      RT has become the cornerstone of adjuvant treatment of colorectal and gastric
      cancer. In view of this, we elected to evaluate the effect of flavopiridol on
      potentiating RT-induced apoptosis in the human colon cancer cell line HCT-116 and
      the gastric cancer cell line MKN-74. EXPERIMENTAL DESIGN: The efficacy of
      combination of gamma-irradiation and flavopiridol was tested in vitro in MKN-74
      and HCT-116 cells and correlated to changes in p21 expression. HCT-116 cells were
      also established as tumors in nude mice and treated with gamma-irradiation and
      flavopiridol either as single agents or in sequential combinations such that
      flavopiridol was either given 7 h before, concomitantly, or 3 and 7 h after gamma
      irradiation. RESULTS: Flavopiridol significantly enhanced the induction of
      apoptosis by gamma-irradiation in both cell lines as measured by quantitative
      fluorescent microscopy, caspase-3 activation, poly(ADP-ribose) polymerase
      cleavage, and cytochrome c release. To achieve the best effect, it was important
      to expose the tumor cells to gamma-irradiation before the flavopiridol. This
      sequence dependence was confirmed in vivo. When gamma-irradiation was
      administered 7 h before flavopiridol, 42% of the tumor-bearing animals were
      rendered disease free, compared with no animals treated with either gamma
      irradiation or flavopiridol alone. Examination of the p21 status of HCT-116 and
      MKN-74 cells, after treatment with sequential gamma-irradiation and flavopiridol,
      indicated a loss of p21 protein expression. Loss of p21 was mainly due to
      cleavage by caspases. HCT-116 cells that lack p21 (p21(-/-)) also exhibited
      sensitization to gamma-irradiation and showed an even greater enhancement of
      gamma-irradiation-induced apoptosis by flavopiridol when compared with the
      parental HCT-116 cells. CONCLUSIONS: These studies indicate that gamma
      irradiation followed by flavopiridol enhances apoptosis and yields significantly
      increased tumor regressions and cures that are not achievable with radiation
      alone. These results indicate that flavopiridol can potently enhance the effect
      of gamma-radiation both in vitro and in vivo and may provide a new means to treat
      patients with locally advanced gastrointestinal cancers.

PMID- 14676133
TI  - The farnesyltransferase inhibitor R115777 reduces hypoxia and matrix
      metalloproteinase 2 expression in human glioma xenograft.
AB  - PURPOSE: The high-grade primary brain tumors, glioblastoma, of extremely bad
      prognosis contain large regions of hypoxia known to be involved in the chemo- and
      radioresistance. We demonstrated previously that radioresistant human wild-type
      Ras U87 glioblastoma can be radiosensitized in vitro by the specific
      farnesyltransferase inhibitor R115777. The aim of this study was to analyze the
      effect of this compound on the hypoxic status and the vascularization of this
      tumor. EXPERIMENTAL DESIGN: U87 xenografts bearing mice were treated with 100
      mg/kg of R115777 b.i.d. during 4 days. Hypoxia was assessed by measuring the
      binding of hypoxic cell marker pentafluorinated 2-nitroimidazole.
      Immunohistochemistry was performed to analyze angiogenesis and metalloproteinase
      2 expression. RESULTS: We demonstrated here that R115777 treatment induced a
      significant oxygenation of U87 xenografts (P<0.001) associated with a decrease of
      hypoxia-inducible factor 1alpha expression. This reduction of hypoxia was not due
      to a decrease of tumor size after R115777 treatment. This oxygenation was
      associated with a change in vessel morphology and with a significant decrease of
      the vessel density. Moreover, R115777 treatment reduced matrix metalloproteinase
      2 expression in xenografts and inhibited matrix metalloproteinase 2 activity in
      vitro. These data strongly suggest that R115777 could increase this tumor
      oxygenation at least by interacting with angiogenesis. CONCLUSION: Our results
      demonstrate that R115777 treatment inhibits different pathways leading to the
      radioresistance of wild-type Ras expressing glioblastoma, including intrinsic
      radioresistance, hypoxia, and angiogenesis. These combined effects on
      glioblastoma underline the interest of associating R115777 with radiotherapy as a
      new treatment of these tumors of catastrophic prognosis.

PMID- 14676134
TI  - Should B-type natriuretic peptide be measured routinely to guide the diagnosis
      and management of chronic heart failure?

PMID- 14676135
TI  - Apoptosis inhibitors for heart disease.

PMID- 14676136
TI  - Explaining how "high-grade" systemic inflammation accelerates vascular risk in
      rheumatoid arthritis.
AB  - There is intense interest in mechanisms whereby low-grade inflammation could
      interact with conventional and novel vascular risk factors to promote the
      atheromatous lesion. Patients with rheumatoid arthritis (RA), who by definition
      manifest persistent high levels of inflammation, are at greater risk of
      developing cardiovascular disease. Mechanisms mediating this enhanced risk are
      ill defined. On the basis of available evidence, we argue here that the systemic
      inflammatory response in RA is critical to accelerated atherogenesis operating
      via accentuation of established and novel risk factor pathways. By implication,
      long-term suppression of the systemic inflammatory response in RA should be
      effective in reducing risk of coronary heart disease. Early epidemiological
      observational and clinical studies are commensurate with this hypothesis. By
      contrast, risk factor modulation with conventional agents, such as statins, may
      provide unpredictable clinical benefit in the context of uncontrolled systemic
      inflammatory parameters. Unraveling such complex relationships in which
      exaggerated inflammation-risk factor interactions are prevalent may elicit novel
      insights to effector mechanisms in vascular disease generally.

PMID- 14676137
TI  - Images in cardiovascular medicine. ST-segment elevation in an unresponsive
      patient.

PMID- 14676139
TI  - Impact of type 2 diabetes mellitus on sympathetic neural mechanisms in
      hypertension.
AB  - BACKGROUND: Essential hypertension (EHT) is a major cardiovascular risk factor,
      and the additional presence of type 2 diabetes mellitus (DM2) increases this
      risk. However, although the sympathetic nerve hyperactivity of EHT is known to
      play a role in cardiovascular risk, the level of sympathetic nerve activity is
      known neither in DM2 nor in hypertensive type 2 diabetic patients (EHT+DM2).
      Therefore, we planned to quantify the vasoconstrictor sympathetic nerve activity
      in patients with EHT+DM2 and with DM2 relative to that in matched groups with EHT
      and normal blood pressure (NT). METHODS AND RESULTS: In 68 closely matched
      subjects with EHT+DM2 (n=17), DM2 (n=17), EHT (n=17), and NT (n=17), we measured
      resting muscle sympathetic nerve activity as the mean frequency of multiunit
      bursts (MSNA) and of single units (s-MSNA) with defined vasoconstrictor
      properties. The s-MSNA in EHT+DM2 (97+/-3.8 impulses/100 beats) was greater (at
      least P<0.001) than in EHT (69+/-3.4 impulses/100 beats) and DM2 (78+/-4.1
      impulses/100 beats), and all these were significantly greater (at least P<0.01)
      than in NT (53+/-3.3 impulses/100 beats) despite similar age and body mass index.
      The MSNA followed a similar trend. In addition, the level of insulin was also
      raised in EHT+DM2 (20.4+/-3.6 microU/mL) and DM2 (18.1+/-3.1 microU/mL; at least
      P<0.05) compared with HT or NT. CONCLUSIONS: Patients with EHT+DM2, EHT, or DM2
      had central sympathetic hyperactivity, although plasma insulin levels were raised
      only in EHT+DM2 and DM2. The combination of EHT and DM2 resulted in the greatest
      sympathetic hyperactivity and level of plasma insulin, and this hyperactivity
      could constitute a mechanism for the increased risks of this condition.

PMID- 14676140
TI  - Targeting of apoptotic macrophages and experimental atheroma with radiolabeled
      annexin V: a technique with potential for noninvasive imaging of vulnerable
      plaque.
AB  - BACKGROUND: Apoptosis is common in advanced human atheroma and contributes to
      plaque instability. Because annexin V has a high affinity for exposed
      phosphatidylserine on apoptotic cells, radiolabeled annexin V may be used for
      noninvasive detection of apoptosis in atherosclerotic lesions. METHODS AND
      RESULTS: Atherosclerotic plaques were produced in 5 rabbits by
      deendothelialization of the infradiaphragmatic aorta followed by 12 weeks of
      cholesterol diet; 5 controls were studied without manipulation. Animals were
      injected with human recombinant annexin V labeled with technetium-99m before
      imaging. Aortas were explanted for ex vivo imaging, macroautoradiography, and
      histological characterization of plaque. Radiolabeled annexin V cleared rapidly
      from the circulation (T1/2, alpha 9 and beta 46 minutes). There was intense
      uptake of radiolabel within lesions by 2 hours; no uptake was seen in controls.
      The results were confirmed in the ex vivo imaging of the explanted aorta.
      Quantitative annexin uptake was 9.3-fold higher in lesion versus nonlesion areas;
      the lesion-to-blood ratio was 3.0+/-0.37. Annexin uptake paralleled lesion
      severity and macrophage burden; no correlation was observed with smooth muscle
      cells. DNA fragmentation staining of apoptotic nuclei was increased in advanced
      lesions with evolving necrotic cores, predominantly in macrophages; the uptake of
      radiolabel correlated with the apoptotic index. CONCLUSIONS: Because annexin V
      clears rapidly from blood and targets apoptotic macrophage population, it should
      constitute an attractive imaging agent for the noninvasive detection of unstable
      atherosclerotic plaques.

PMID- 14676141
TI  - High omega-3 fatty acid content in alpine cheese: the basis for an alpine
      paradox.
AB  - BACKGROUND: Alpha-linolenic acid (ALA) may protect from cardiovascular disease.
      Because fresh alpine grass contains high amounts of ALA, we hypothesized that the
      levels of omega-3 fatty acids would concentrate to nutritional relevance in the
      cheese of milk from cows with alpine grass feeding compared with cheese from
      silage and concentrate feeding; the newly available cheese produced from cows fed
      with linseed supplementation should contain even higher ALA concentrations.
      METHODS AND RESULTS: Forty different cheeses were analyzed by gas chromatography
      for their fatty acid profile: (1) 12 from well-defined alpine regions around
      Gstaad, Switzerland; (2) 7 commercially available English cheddar cheeses; (3) 6
      cheeses from cows fed with linseed supplementation; (4) 7 industrial-type
      Emmentals; and (5) 8 alpine cheeses with partial silage feeding. The alpine
      cheese contained 4 times more linolenic acid (C18:3omega-3) compared with
      cheddar, more total omega-3 fatty acids, and showed a significantly lower n
      6:omega-3 ratio. Conjugated linoleic acid (C18:2 c9/t11) was 3-fold higher,
      whereas the amount of palmitic acid was 20% lower. The Emmental reached 40% of
      the ALA content compared with alpine cheese, and surprisingly, cheese from
      linseed-supplemented cows contained only 49% of that of the alpine cheese
      (P<0.001 for each trait in the 5 cheese groups). CONCLUSIONS: Cheese made of milk
      from cows grazed on alpine pastures had a more favorable fatty acid profile than
      all other cheese types. Alpine cheese may be a relevant source of ALA and other
      cardioprotective fatty acids.

PMID- 14676142
TI  - Estrogen-mediated, endothelial nitric oxide synthase-dependent mobilization of
      bone marrow-derived endothelial progenitor cells contributes to
      reendothelialization after arterial injury.
AB  - BACKGROUND: We hypothesized that estrogen-induced acceleration of
      reendothelialization might be mediated in part by effects involving mobilization
      and incorporation of bone marrow-derived endothelial progenitor cells (EPCs).
      METHODS AND RESULTS: Carotid injury was induced in ovariectomized wild-type mice
      receiving either 17beta-estradiol or placebo. Estradiol treatment significantly
      accelerated reendothelialization of injured arterial segments within 7 days and
      resulted in a significant reduction of medial thickness 14 and 21 days after the
      injury. Significant increases in circulating EPCs 3 days after the injury were
      observed in the estradiol group compared with placebo-treated mice. These data
      were further supported by fluorescence-activated cell sorting analysis, which
      disclosed a significant increase in Sca-1/Flk-1-positive cells in estradiol
      versus control mice. To evaluate the effects of estradiol on bone marrow-derived
      EPC incorporation at sites of reendothelialization, carotid injury was
      established in ovariectomized wild-type mice transplanted with bone marrow from
      transgenic donors expressing beta-galactosidase transcriptionally regulated by
      the Tie-2 promoter. Significantly greater numbers of X-gal-positive cells were
      observed at reendothelialized areas in the estradiol group 3 days after injury as
      compared with placebo. Fluorescent immunohistochemistry 14 days after the injury
      documented a marked increase in cells expressing both beta-gal, indicating bone
      marrow origin and Tie-2 expression, and isolectin B4, also indicating endothelial
      lineage, in the estradiol group compared with control. In contrast, estradiol did
      not accelerate reendothelialization or augment EPC mobilization into the
      peripheral circulation after injury in endothelial nitric oxide synthase
      deficient mice (eNOS-/-). Furthermore, estradiol exhibited direct stimulatory
      effects on EPC mitogenic and migration activity and inhibited EPC apoptosis.
      CONCLUSIONS: Estradiol accelerates reendothelialization and attenuates medial
      thickening after carotid injury in part by augmenting mobilization and
      proliferation of bone marrow-derived EPCs and their incorporation into the
      recovering endothelium at the site of injury.

PMID- 14676143
TI  - Expression of cholesterol sulfotransferase (SULT2B1b) in human platelets.
AB  - BACKGROUND: Cholesterol sulfate, the most important sterol sulfate in the human
      circulation, has emerged as a multifaceted molecule. Among its many demonstrated
      regulatory actions is its ability to influence blood clotting and fibrinolysis.
      Additionally, cholesterol sulfate is a constituent of human platelets, where it
      has been shown to support platelet aggregation. METHODS AND RESULTS: We have
      documented the presence of the enzyme (SULT2B1b) that sulfonates cholesterol in
      human platelets and examined the influence of plasma lipoproteins on the
      expression and activity of this enzyme. SULT2B1b mRNA was detected by reverse
      transcription-polymerase chain reaction and found to be the only steroid/sterol
      sulfotransferase expressed in these discoid anucleate particles. Using real-time
      polymerase chain reaction for quantification, we found that the level of SULT2B1b
      mRNA in platelets was maintained at 4 degrees C but substantially diminished over
      a period of 4 hours at 37 degrees C. The loss of SULT2B1b mRNA, however, was
      markedly reduced in the presence of HDL but not LDL. The stabilizing influence of
      HDL was attributable specifically to its apolipoprotein (apo) A-I component,
      whereas apoA-II and apoE were without effect. Importantly, there was a direct
      correlation between platelet SULT2B1b mRNA and protein levels in the presence or
      absence of lipoprotein that was reflected in enzymatic activity and cholesterol
      sulfate production. CONCLUSIONS: Human platelets selectively express SULT2B1b,
      the physiological cholesterol sulfotransferase. Furthermore, the stability of
      SULT2B1b mRNA and protein in platelets maintained at 37 degrees C is subject to
      regulation by the apoA-I component of HDL.

PMID- 14676144
TI  - Association of the metabolic syndrome with history of myocardial infarction and
      stroke in the Third National Health and Nutrition Examination Survey.
AB  - BACKGROUND: The combination of cardiovascular risk factors known as the metabolic
      syndrome is receiving increased attention from physicians, but data on the
      syndrome's association with morbidity are limited. METHODS AND RESULTS: Applying
      National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III)
      criteria, we evaluated 10 357 NHANES III subjects for the 5 component conditions
      of the metabolic syndrome: insulin resistance, abdominal obesity based on waist
      circumference, hypertriglyceridemia, low HDL cholesterol (HDL-C), and
      hypertension, as well as the full syndrome, defined as at least 3 of the 5
      conditions. Logistic regression was used to estimate the cross-sectional
      association of the syndrome and each of its 5 component conditions separately
      with history of myocardial infarction (MI), stroke, and either MI or stroke
      (MI/stroke). Models were adjusted for age, sex, race, and cigarette smoking. The
      metabolic syndrome was significantly related in multivariate analysis to MI (OR,
      2.01; 95% CI, 1.53 to 2.64), stroke (OR, 2.16; 95% CI, 1.48 to 3.16), and
      MI/stroke (OR, 2.05; 95% CI, 1.64 to 2.57). The syndrome was significantly
      associated with MI/stroke in both women and men. Among the component conditions,
      insulin resistance (OR, 1.30; 95% CI, 1.03 to 1.66), low HDL-C (OR, 1.35; 95% CI,
      1.05 to 1.74), hypertension (OR, 1.44; 95% CI, 1.00 to 2.08), and
      hypertriglyceridemia (OR, 1.66; 95% CI=1.20 to 2.30) were independently and
      significantly related to MI/stroke. CONCLUSIONS: These results indicate a strong,
      consistent relationship of the metabolic syndrome with prevalent MI and stroke.

PMID- 14676145
TI  - Cardiovascular mortality and long-term exposure to particulate air pollution:
      epidemiological evidence of general pathophysiological pathways of disease.
AB  - BACKGROUND: Epidemiologic studies have linked long-term exposure to fine
      particulate matter air pollution (PM) to broad cause-of-death mortality.
      Associations with specific cardiopulmonary diseases might be useful in exploring
      potential mechanistic pathways linking exposure and mortality. METHODS AND
      RESULTS: General pathophysiological pathways linking long-term PM exposure with
      mortality and expected patterns of PM mortality with specific causes of death
      were proposed a priori. Vital status, risk factor, and cause-of-death data,
      collected by the American Cancer Society as part of the Cancer Prevention II
      study, were linked with air pollution data from United States metropolitan areas.
      Cox Proportional Hazard regression models were used to estimate PM-mortality
      associations with specific causes of death. Long-term PM exposures were most
      strongly associated with mortality attributable to ischemic heart disease,
      dysrhythmias, heart failure, and cardiac arrest. For these cardiovascular causes
      of death, a 10-microg/m3 elevation in fine PM was associated with 8% to 18%
      increases in mortality risk, with comparable or larger risks being observed for
      smokers relative to nonsmokers. Mortality attributable to respiratory disease had
      relatively weak associations. CONCLUSIONS: Fine particulate air pollution is a
      risk factor for cause-specific cardiovascular disease mortality via mechanisms
      that likely include pulmonary and systemic inflammation, accelerated
      atherosclerosis, and altered cardiac autonomic function. Although smoking is a
      much larger risk factor for cardiovascular disease mortality, exposure to fine PM
      imposes additional effects that seem to be at least additive to if not
      synergistic with smoking.

PMID- 14676146
TI  - Nuclear factor-kappaB protects the adult cardiac myocyte against ischemia-induced
      apoptosis in a murine model of acute myocardial infarction.
AB  - BACKGROUND: Previous studies have shown that tumor necrosis factor (TNF) confers
      cytoprotective responses in cardiac myocytes. However, the mechanisms for the
      cytoprotective effects of TNF remain unknown. Given that TNF signals through
      nuclear factor kappaB (NF-kappaB) and given that NF-kappaB mediates
      cytoprotective responses, we asked whether NF-kappaB activation conferred
      cytoprotective responses in acute myocardial ischemia/infarction. METHODS AND
      RESULTS: We examined infarct size and the prevalence of apoptosis in transgenic
      mice harboring cardiac-restricted expression of a mutated IkappaBalpha protein
      (IkappaBalphaDeltaN) that prevents nuclear translocation of NF-kappaB in cardiac
      myocytes. Triphenyltetrazolium chloride staining showed that infarct size was
      approximately 50% greater (P<0.02) in the IkappaBalphaDeltaN mice compared with
      littermate controls at 24 hours. The prevalence of cardiac myocyte apoptosis was
      significantly greater (P<0.008) in the IkappaBalphaDeltaN mice compared with the
      littermate control mice 3 and 6 hours after left anterior descending occlusion.
      To explore the mechanism for these findings, we examined protein levels of c
      IAP1, c-IAP2, and Bcl-2 as well as manganese superoxide dismutase and c-Jun NH2
      terminal kinase activity. These studies showed that protein levels of c-IAP1 and
      Bcl-2 were significantly lower in the IkappaBalphaDeltaN mice, whereas there was
      no change in c-IAP2 levels, manganese superoxide dismutase, or c-Jun NH2-terminal
      kinase activity. CONCLUSIONS: Transgenic mice with a defect in activation of NF
      kappaB have increased susceptibility to tissue injury after acute left anterior
      descending occlusion. These studies suggest that the cytoprotective effects of NF
      kappaB are mediated, at least in part, by Bcl-2 or c-IAP1.

PMID- 14676147
TI  - Cardiac systolic and diastolic dysfunction after a cholesterol-rich diet.
AB  - BACKGROUND: Although hypercholesterolemia is a well-established risk factor for
      coronary artery disease, little is known regarding its direct effects on cardiac
      function. METHODS AND RESULTS: We examined the effects of cholesterol feeding
      (0.5%) on cardiac function in rabbits. After 10 weeks, both systolic shortening
      and diastolic relaxation rates were impaired without any change in aortic
      pressure or ventricular hypertrophy. However, sarcoplasmic/endoplasmic reticulum
      Ca2+-ATPase (SERCA)-2 mRNA levels were reduced within 4 days after initiation of
      cholesterol feeding. After this effect, SERCA-2 protein and SERCA-mediated Ca
      uptake into sarcoplasmic reticulum vesicles were impaired, and the ratio of MHC
      beta to MHC-alpha mRNA increased 5-fold. Suppression of the SERCA-2 message
      correlated temporally with enrichment of the cardiac sarcolemma with cholesterol.
      CONCLUSIONS: These data demonstrate that dietary hypercholesterolemia induces a
      "cholesterol cardiomyopathy" characterized by systolic and diastolic dysfunction.
      These alterations were independent of vascular disease and demonstrate a dietary
      link to cardiac dysfunction.

PMID- 14676148
TI  - Sudden death associated with short-QT syndrome linked to mutations in HERG.
AB  - BACKGROUND: Sudden cardiac death takes the lives of more than 300 000 Americans
      annually. Malignant ventricular arrhythmias occurring in individuals with
      structurally normal hearts account for a subgroup of these sudden deaths. The
      present study describes the genetic basis for a new clinical entity characterized
      by sudden death and short-QT intervals in the ECG. METHODS AND RESULTS: Three
      families with hereditary short-QT syndrome and a high incidence of ventricular
      arrhythmias and sudden cardiac death were studied. In 2 of them, we identified 2
      different missense mutations resulting in the same amino acid change (N588K) in
      the S5-P loop region of the cardiac IKr channel HERG (KCNH2). The mutations
      dramatically increase IKr, leading to heterogeneous abbreviation of action
      potential duration and refractoriness, and reduce the affinity of the channels to
      IKr blockers. CONCLUSIONS: We demonstrate a novel genetic and biophysical
      mechanism responsible for sudden death in infants, children, and young adults
      caused by mutations in KCNH2. The occurrence of sudden cardiac death in the first
      12 months of life in 2 patients suggests the possibility of a link between KCNH2
      gain of function mutations and sudden infant death syndrome. KCNH2 is the binding
      target for a wide spectrum of cardiac and noncardiac pharmacological compounds.
      Our findings may provide better understanding of drug interaction with KCNH2 and
      have implications for diagnosis and therapy of this and other arrhythmogenic
      diseases.

PMID- 14676150
TI  - Tracheostomy in preterm infants: current trends.
AB  - OBJECTIVE: To study the indications for and outcomes of tracheostomy in a
      population of preterm infants. DESIGN: Retrospective analysis of case records.
      SETTING: Two university-affiliated tertiary care children's hospitals. Patients
      We identified premature infants who required tracheostomies from January 1, 1997,
      through January 31, 2001. Information on weight, gestational age, comorbid
      conditions, indication for tracheostomy, and outcomes was collected. Infants were
      divided by birth weight into group 1 (<1000 g; n = 19 [very low birth weight])
      and group 2 (> or =1000 g; n = 14). Comorbid conditions were scored and a total
      score was calculated for each patient. RESULTS: Group 1 had a higher incidence of
      patent ductus arteriosus, bronchopulmonary dysplasia, intraventricular
      hemorrhage, and retinopathy of prematurity. The incidence of congenital or
      genetic defects was equal in groups 1 and 2 (11 infants [58%] and 8 infants
      [57%], respectively). Group 1 had a higher average number of failed extubations
      (5.17 vs 3.18) and a higher oxygen requirement (48.7% vs 30.3%) compared with
      group 2. Weight at tracheostomy was essentially equal in groups 1 and 2 (3.6 vs
      3.7 kg). Subglottic stenosis and laryngotracheomalacia were equally common
      findings in groups 1 and 2. The average comorbidity score for group 1 was higher
      than that for group 2 (6.7 vs 2.8). The most common indication for tracheostomy
      was ventilatory dependence (n = 24 [73%]), compared with airway obstruction (n =
      6 [18%]) and pulmonary toilet (n = 3 [9%]). Overall, 6 patients (18%) had a
      complication related to the tracheostomy. CONCLUSIONS: Severity of pulmonary
      disease was the most significant factor associated with the need for tracheostomy
      in preterm infants. A tracheostomy can safely be performed in these infants with
      minimal morbidity.

PMID- 14676151
TI  - Predictors of remission in juvenile-onset recurrent respiratory papillomatosis.
AB  - OBJECTIVE: To determine factors associated with remission of juvenile-onset
      recurrent respiratory papillomatosis (JORRP). DESIGN: Longitudinal study.
      SETTING: Twenty-two tertiary care centers located across the United States. STUDY
      PARTICIPANTS AND METHODS: The study included 165 patients diagnosed as having
      JORRP between January 1, 1997, and December 31, 2000. Kaplan-Meier curves and Cox
      proportional hazards models were used to determine associations between
      predictors and remission. INTERVENTIONS: Surgical excision and drug therapy. MAIN
      OUTCOME MEASURES: Remission of JORRP, defined as no surgical procedures for at
      least 1 year, as associated with age at diagnosis, drug therapy in the first year
      after diagnosis, number of surgical procedures in the first year after diagnosis,
      and number of anatomical sites of disease at diagnosis. Demographic factors (sex
      and race) and Medicaid status were also evaluated. RESULTS: Older age at
      diagnosis was positively associated with remission of JORRP (hazards ratio for
      every increase of 1 year in age, 1.13; 95% confidence interval, 1.03-1.23).
      CONCLUSIONS: Younger children were found to have persistent disease and often
      underwent an increased number of surgical procedures in the first year after
      diagnosis of JORRP. Sex and race were not important factors in determining
      remission.

PMID- 14676152
TI  - Evaluation of a new device for home cardiorespiratory recording in children.
AB  - OBJECTIVE: To evaluate the feasibility of using a new home cardiorespiratory
      recording device (HCRD) in children. DESIGN: Cross-sectional study. PATIENTS:
      Consecutive children scheduled for adenotonsillectomy to treat habitual snoring
      and/or apneas at otorhinolaryngology clinics in 2 academic and 7 general
      hospitals. INTERVENTION: Single-night unattended home cardiorespiratory recording
      prior to adenotonsillectomy using the HCRD. MAIN OUTCOME MEASURES: Number of
      technically acceptable recordings and successful recordings with artifact-free
      signals (respiration, saturation, and nasal flow) present for sufficient duration
      to allow scoring of the polysomnogram and to make a diagnosis. RESULTS: Of 53
      eligible children, 24 participated in the study. The main reason for
      nonparticipation was refusal of caregivers (n = 16). Mean (SD) age of
      participants was 4.2 (1.6) years; median Brouillette obstructive sleep apnea
      score was 2.54. Technically acceptable recordings were obtained in 18 children
      (75%). Only 7 recordings (29%) were classified as successful. The poorest signal
      quality was obtained from the nasal cannula. CONCLUSION: Based on strict scoring
      criteria in this study, the results of single-night unattended recordings at home
      with the HCRD fell short of expectations.

PMID- 14676153
TI  - Microdissection needle tonsillectomy and postoperative pain: a pilot study.
AB  - OBJECTIVE: To determine whether microdissection needle cautery for tonsillectomy
      results in decreased postoperative pain when compared with standard
      electrocautery. DESIGN AND SETTING: A randomized prospective study of 2 groups of
      young children in an academic pediatric otolaryngology practice. SUBJECTS: Forty
      two healthy children between the ages of 4 and 12 years. INTERVENTION: The 42
      children were randomly assigned to 2 groups: in group A, the tonsillectomy was
      performed with standard monopolar electrocautery tip at 20 W; in group B, the
      microdissection needle was used at 8 W. The same surgeon performed each
      tonsillectomy. Other aspects of the procedure were constant, including patient
      positioning, intraoperative injection of 0.25% bupivacaine hydrochoride
      (Marcaine), a weight-appropriate dose of steroids, and the use of postoperative
      antibiotics. OUTCOME MEASURES: The subjective measure of postoperative pain was a
      questionnaire based on a standard visual analog scale ranging from 0 to 10. More
      objective measures included the doses of pain medications consumed and the
      tolerance of oral intake. RESULTS: There was no statistical significant
      difference in the amount of intraoperative hemorrhage between groups (P>. 01).
      Operative time was on average 3.2 minutes longer in group B (11 minutes vs 7.8
      minutes). The postoperative pain as measured by the visual analog scale was
      significantly different on days 3, 4, and 5 in group B (P<.05). This difference
      in pain correlated to differences in the number of doses of pain medications used
      on the same days. There was no statistically significant difference between the 2
      groups concerning the amount of fluids tolerated (P>.01). CONCLUSIONS: Without
      any increase in complications, subjective and objective measurement showed that
      the use of the microdissection needle resulted in significantly less
      postoperative pain by day 3.

PMID- 14676154
TI  - Controlled risk of stenosis after surgical excision of laryngeal hemangioma.
AB  - OBJECTIVE: To evaluate the risk of subglottic stenosis after surgical excision of
      congenital subglottic hemangioma. DESIGN: Retrospective analysis and case series.
      SETTING: Tertiary care teaching hospital. PATIENTS: A total of 13 pediatric
      patients diagnosed with subglottic hemangioma with unilateral, bilateral, or
      circular lesions and more than 50% airway obstruction between 1992 and 2001.
      INTERVENTION: Open surgical excision was performed as a single-stage procedure
      either as primary or secondary intention. The cricoid cartilage was left open at
      the end of the procedure. Postoperative intubation was carried out in a pediatric
      intensive care unit. MAIN OUTCOME MEASURE: An adequate airway after surgical
      excision. RESULTS: All patients were successfully extubated. No recurrence was
      noted. Three patients developed subglottic stenosis, two grade 1 and one grade 2.
      All 3 showed a favorable outcome and did not require reintubation. One needed
      endoscopic management of the stenosis. Of these 3 cases, 2 occurred after carbon
      dioxide laser treatment (out of 3) and 1 after circumferential dissection (out of
      3). CONCLUSIONS: Extubation after surgery was successful in all cases of
      subglottic hemangioma. Risk of subglottic stenosis was limited and occurred only
      after circumferential dissection, especially if associated with prior traumatic
      laser damage of the hemangioma.

PMID- 14676155
TI  - Validation of a transfusion prediction model in head and neck cancer surgery.
AB  - BACKGROUND: Allogeneic transfusions are necessary in 14% to 80% of patients
      undergoing major head and neck cancer surgery. Defining the risk for receiving
      allogeneic transfusion allows for informed decisions regarding appropriateness of
      type and crossmatch, preoperative autologous blood donation, and priming with
      erythropoietin. Based on logistic regression analysis of transfusion risk factors
      in 438 patients, we developed a transfusion prediction risk assessment (TPRA)
      model to determine the need for transfusion based on the preoperative hemoglobin
      value, tumor stage, and need for flap reconstruction. OBJECTIVE: To examine the
      utility of this TPRA model in clinical practice by assessing the performance of
      the model in a validation set of patients. METHODS: Between 1996 and 1999, 125
      consecutive patients entered into a clinical care pathway underwent major
      surgical procedures. The ability of the model to discriminate between patients
      requiring and those not requiring transfusion was assessed using the area under
      the receiver operating characteristic curve. The agreement between actual and
      predicted risks was tested using the chi2 goodness-of-fit statistic. RESULTS: The
      overall transfusion rate was 25%. A 1-U transfusion was required in 7 patients,
      and multiple units were necessary for 24 patients. Flap reconstruction was
      required in 63 patients, 44 patients had preoperative anemia by normative values,
      and 64 had T3/T4 tumors. Among the low-risk non-T3/T4 patients whose preoperative
      hemoglobin level was normal, the actual/predicted transfusion rate without flap
      reconstruction was 10%/2%. For high-risk patients with T3/T4 tumors, anemia, and
      flap reconstruction, the actual/predicted transfusion rate was 43%/65%. The area
      under the receiver operating characteristic curve was 0.72. The goodness-of-fit
      statistic indicated lack of fit of the original model, but a recalibrated model
      fit the observed data well. CONCLUSIONS: In general, the TPRA model identifies
      patients at low or high risk for allogeneic transfusion and provides guidelines
      for preoperative counseling regarding the risk of receiving a transfusion.
      Knowledge of a patient's risk can help direct cost-effective utilization of type
      and crossmatch, preoperative autologous blood donation, and preoperative priming
      with erythropoietin.

PMID- 14676156
TI  - Quality of life following surgery for anterior skull base tumors.
AB  - OBJECTIVES: To evaluate patients' quality of life (QOL) after surgical
      extirpation of anterior skull base tumors, to elucidate different QOL domains,
      and to define possible predictors of functional outcome postoperatively. DESIGN:
      Retrospective survey. SETTING: University-affiliated medical center.
      PARTICIPANTS: Sixty-nine patients (76 consecutive cases) who underwent subcranial
      surgery between 1994 and 2002 for extirpation of anterior skull base tumors. MAIN
      OUTCOME MEASURE: A multidimensional, disease-specific questionnaire with 39 items
      was used. Six relevant domains of QOL were assessed: role of performance,
      physical functioning, vitality, pain, specific symptoms, and impact on emotions.
      RESULTS: The response rate for completing the questionnaire was 98% (40/41) after
      excluding patients who died (n = 13), were lost to follow-up (n = 10), and were
      operated on within 3 months of commencement of the study (n = 5). Thirty patients
      (74%) reported a significant improvement or no change in overall QOL within 6
      months after surgery. The worst impact of surgery on the patients' QOL was on
      their financial status and emotional state. The most influential factor on QOL
      was malignancy leading to a significant decrease in the overall score.
      Radiotherapy, old age, comorbidity, and wide resection also significantly
      worsened QOL scores of specific domains. CONCLUSION: After subcranial extirpation
      of anterior skull base tumors, the overall outcome of the patients is good. Old
      age, malignancy, comorbidity, wide resection, and radiotherapy are negative
      prognostic factors for these patients' QOL.

PMID- 14676157
TI  - A-mode ultrasound-based registration in computer-aided surgery of the skull.
AB  - OBJECTIVE: To evaluate the integration and accuracy of A (amplitude)-mode
      ultrasound-based surface matching for noninvasive registration of the head into a
      frameless computer-aided surgery system for otorhinology and skull base surgery.
      DESIGN: Experimental study and case series. SETTING: Academic medical center.
      PATIENTS: Twelve patients underwent anterior and paranasal skull base surgery
      with the routine use of a computer-aided surgery system. INTERVENTIONS: A
      computer-aided surgery system, based on an optoelectronic localizer, was used to
      track the skull and the surgical tools, including the A-mode ultrasound probe.
      The A-mode probe was a 10-MHz immersion transducer. An acoustic lens attached to
      the transducer focused the ultrasonic beam to a depth of 1 to 10 mm. Accuracy
      tests were performed for the ultrasound setup. Different surface point
      distributions were evaluated with respect to matching accuracy on a human cadaver
      skull specimen equipped with fiducial markers. The matching comparison was based
      on the fiducial registration error. For the clinical evaluation, the laboratory
      setup was transferred to the operating room. MAIN OUTCOME MEASURES: Noninvasive
      registration of the skull by using A-mode ultrasound in computer-aided surgery
      (practical and clinical measurements). RESULTS: The accuracy tests on the human
      skull specimen revealed that the mean +/- SD fiducial registration error was 1.00
      +/- 0.19 mm in the best series for A-mode ultrasound surface matchings and was
      robust with respect to different sets of surface points. The mean +/- SD root
      mean square error from the 12 A-mode ultrasound matchings in the patient study
      was 0.49 +/- 0.20 mm. CONCLUSION: A-mode ultrasound surface matching can be used
      as a noninvasive and accurate registration procedure in computer-aided surgery of
      the head.

PMID- 14676158
TI  - Postoperative complications after en bloc salvage surgery for head and neck
      cancer.
AB  - OBJECTIVE: To analyze the frequency of and risk factors for postoperative
      complications after en bloc salvage surgery for head and neck cancer. DESIGN:
      Retrospective cohort study. SETTING: Patients were evaluated from February 7,
      1990, to November 17, 1999, in a tertiary cancer center hospital. PATIENTS:
      Consecutive sample of 124 patients from the hospital database. Only patients with
      recurrent head and neck squamous cell carcinoma undergoing en bloc salvage
      resection were eligible for the study. MAIN OUTCOME MEASURES: We analyzed the
      frequency of and risk factors for complications after salvage surgery. RESULTS:
      The tumor location was the lip in 6 patients, oral cavity in 55, oropharynx in
      31, larynx in 24, and hypopharynx in 8. Previous treatment was surgery alone in
      20 patients, radiotherapy alone in 68, surgery and radiotherapy in 21, and
      radiotherapy and chemotherapy in 14. An additional patient received chemotherapy
      alone before salvage surgery. The clinical stage of the recurrent tumor was I or
      II in 23 patients and III or IV in 101 patients. Postoperative complications
      occurred in 66 patients (53.2%). Fifty-three patients (42.7%) had minor
      complications, and 23 patients (18.5%) had major ones. There were 4 postoperative
      deaths (3.2%). The major factor associated with the overall occurrence of
      postoperative complications was the clinical stage of the recurrent tumor (P
      =.02). The occurrence of minor complications correlated with the previously
      treated site, with complications occurring more often in patients undergoing
      locoregional vs local treatment (P =.04). Major complications were associated
      with the time between initial treatment and salvage surgery (P =.05).
      CONCLUSIONS: Salvage surgery can be performed with acceptable rates of
      postoperative complications. The clinical stage of the recurrent tumor and the
      previous site treated were the 2 major factors associated with the occurrence of
      postoperative complications.

PMID- 14676159
TI  - Significance of c-Myc and Bcl-2 protein expression in nasopharyngeal carcinoma.
AB  - OBJECTIVE: To investigate the relationship between oncogene protein expression
      and nasopharyngeal carcinoma outcome. DESIGN: Tumor samples from 51 patients with
      nasopharyngeal carcinoma were analyzed by immunohistochemical staining for
      expression of Bcl-2 and c-Myc protein before irradiation. Five-year follow-up
      data were available. RESULTS: Thirty-one (61%) of 51 tumors expressed Bcl-2
      protein, and 29 (57%) of 51 tumors expressed c-Myc protein. In the Bcl-2+ group,
      20 (65%) and 19 (61%) of 31 patients experienced recurrence or died,
      respectively, whereas only 7 (35%) and 5 (25%) of 20 patients with Bcl-2- tumors
      did so. On the other hand, patients with c-Myc+ tumors had lower recurrence and
      death rates (38% [11/29] and 34% [10/29], respectively) than those with c-Myc-
      tumors (73% [16/22] and 64% [14/22], respectively). A statistically significant
      association was confirmed between Bcl-2 and c-Myc positivity and patient outcome.
      CONCLUSION: Expression of Bcl-2 and c-Myc protein seems to be a useful marker to
      reflect irradiation response and to predict illness condition and patient
      outcome.

PMID- 14676160
TI  - Pilomatricoma of the head and neck: a retrospective review of 179 cases.
AB  - OBJECTIVE: To describe the clinical presentations and management of
      pilomatricoma, formerly known as pilomatrixoma, of the head and neck. DESIGN:
      Retrospective study. SETTING: Tertiary care center. PATIENTS: The study included
      179 patients with a diagnosis of pilomatricoma of the head and neck.
      INTERVENTION: All patients underwent surgical excision for pilomatricoma of the
      head and neck between 1991 and 2002. RESULTS: Pilomatricoma occurred at any age
      (mean age, 29.8 years); 45.3% of the cases occurred in patients younger than 18
      years. The female-male ratio was 0.97:1. The average size of the lesion was 1 cm.
      The most common sites of occurrence were the neck (30.2%), cheeks (16.8%), scalp
      (16.2%), and brow and periorbital area (14.0%). Multiple occurrence was found in
      1 case. Two of 179 tumors recurred after surgical excision. CONCLUSIONS: Because
      preoperative diagnosis of pilomatricoma is usually incorrect, careful clinical
      examination and a high index of suspicion would result in a more accurate
      diagnosis. Complete surgical excision is the treatment of choice.
      Otolaryngologists should consider pilomatricoma in the differential diagnosis of
      neck masses.

PMID- 14676161
TI  - Reversible anosmia after amikacin therapy.
AB  - Olfactory disorders are among the rare adverse effects of antibiotic therapy. To
      date, olfactory losses or distortions have been reported after the use of
      doxycycline, amoxicillin, clarithromycin, roxithromycin, kanamycin sulfate, and
      streptomycin sulfate. We describe what we believe to be the first case of
      transient anosmia associated with the use of intravenous amikacin sulfate. The
      appearance of the disorder and its subsequent resolution were demonstrated by
      psychometric testing as well as by chemosensory evoked potentials. Based on the
      well-documented temporal course of the anosmia, there is a probable causal
      correlation between the administration of amikacin and the appearance of the
      olfactory disturbance. However, the exact pathogenesis of the anosmia is still a
      matter of conjecture.

PMID- 14676162
TI  - Expression of urokinase-type plasminogen activator and its receptor in keloids.
AB  - BACKGROUND: The urokinase-mediated plasminogen activation (uPA) system plays a
      central role in a number of cellular processes including tissue remodeling, cell
      migration, and angiogenesis. Elevated uPA activity has also been seen with tumor
      invasion and metastasis in a variety of malignancies. Keloids represent an
      aberrant form of wound healing characterized by uncontrolled growth with invasion
      beyond the margins of the original wound. The regulation of this cellular process
      remains poorly understood. We hypothesize that keloids will have increased
      staining percentage for uPA and its receptor (uPAR) compared with normal scars.
      To our knowledge, no previous studies have examined the relationship of uPAR in
      keloid formation. DESIGN: Analysis of uPAR expression by immunohistochemistry in
      paraffin sections from 20 keloids and 18 normal scars. Expression was graded by a
      dermatopathologist according to percentage of cells staining for uPAR. SETTING:
      University Medical Center (Division of Otolaryngology-Head and Neck Surgery) and
      the Department of Dermatology at the University of Rochester Medical and Dental
      School, Rochester, NY. RESULTS: Of the 20 keloids, 8 (40%) strongly expressed
      uPAR (>50% of cells), while only 4 (22%) of 18 normal scars had similar staining.
      More than half of the normal scars stained minimally for uPAR (<5% staining).
      There was a strong expression of uPAR in the extracellular matrix in 14 (70%) of
      the 20 keloids, while no scar showed uPAR in the extracellular matrix.
      CONCLUSION: Our observation suggests that the uPA system is involved in the
      expansion of keloids beyond the wound margins in part through the degradation of
      the extracellular matrix, a finding that is supported by the strong expression of
      uPAR in the extracellular matrix and collagenous cords in most keloids studied.

PMID- 14676164
TI  - Pathology quiz case: aneurysmal bone cyst (ABC) of the maxilla.

PMID- 14676163
TI  - Gorham Stout syndrome (disappearing bone disease): two additional case reports
      and a review of the literature.
AB  - Gorham-Stout syndrome, or disappearing bone disease, is characterized by the
      proliferation of thin-walled vascular channels associated with regional
      osteolysis. There have been fewer than 150 cases reported in the literature. In
      this clinical report, we describe 2 additional cases of Gorham-Stout syndrome
      affecting the maxillofacial skeleton. We provide a review of the clinical
      diagnosis of this syndrome and describe treatment options.

PMID- 14676165
TI  - Radiology quiz case: Gianturco coil.

PMID- 14676166
TI  - Research training in otolaryngology: is it time to refocus our efforts?

PMID- 14676169
TI  - Shortfalls of imaging diagnostics for allergic fungal sinusitis.

PMID- 14676171
TI  - Correct carboplatin dose?

PMID- 14676173
TI  - Surgical innovation and research.

PMID- 14676174
TI  - Negative side of nasal saline sprays: they can be harmful.

PMID- 14676176
TI  - Research training in otolaryngology.

PMID- 14676177
TI  - Computed tomography of rhinosinusitis in immunodeficient patients: not only
      fungal sinusitis.

PMID- 14676178
TI  - Jury findings of malpractice despite the evidence.

PMID- 14676179
TI  - "Neurocranial restructuring" and homeopathy, neither complementary nor
      alternative.

PMID- 14676180
TI  - Capsule sparing in tonsil surgery: the value of intracapsular tonsillectomy.

PMID- 14676181
TI  - Familial neuro-oromotor dysfunction syndrome with dysmorphia in Dostoyevsky's
      Crime and Punishment.

PMID- 14676182
TI  - You have a friend at the FDA.

PMID- 14676184
TI  - Toward selective covalent inactivation of pathogenic antibodies: a phosphate
      diester analog of vasoactive intestinal peptide that inactivates catalytic
      autoantibodies.
AB  - We report the selective inactivation of proteolytic antibodies (Abs) to an
      autoantigen, the neuropeptide vasoactive intestinal peptide (VIP), by a
      covalently reactive analog (CRA) of VIP containing an electrophilic phosphonate
      diester at the Lys(20) residue. The VIP-CRA was bound irreversibly by a
      monoclonal Ab that catalyzes the hydrolysis of VIP. The reaction with the VIP-CRA
      proceeded more rapidly than with a hapten CRA devoid of the VIP sequence. The
      covalent binding occurred preferentially at the light chain subunit of the Ab.
      Covalent VIP-CRA binding was inhibited by VIP devoid of the phosphonate diester
      group. These results indicate the importance of noncovalent VIP recognition in
      guiding Ab nucleophilic attack on the phosphonate group. Consistent with the
      covalent binding data, the VIP-CRA inhibited catalysis by the recombinant light
      chain of this Ab with potency greater than the hapten-CRA. Catalytic hydrolysis
      of VIP by a polyclonal VIPase autoantibody preparation that cleaves multiple
      peptide bonds located between residues 7 and 22 essentially was inhibited
      completely by the VIP-CRA, suggesting that the electrophilic phosphonate at
      Lys(20) enjoys sufficient conformational freedom to react covalently with Abs
      that cleave different peptide bonds in VIP. These results suggest a novel route
      to antigen-specific covalent targeting of pathogenic Abs.

PMID- 14676185
TI  - A role for apical membrane antigen 1 during invasion of hepatocytes by Plasmodium
      falciparum sporozoites.
AB  - Plasmodium sporozoites are transmitted through the bite of infected mosquitoes
      and invade hepatocytes as a first and obligatory step of the parasite life cycle
      in man. Hepatocyte invasion involves proteins secreted from parasite vesicles
      called micronemes, the most characterized being the thrombospondin-related
      adhesive protein (TRAP). Here we investigated the expression and function of
      another microneme protein recently identified in Plasmodium falciparum
      sporozoites, apical membrane antigen 1 (AMA-1). P. falciparum AMA-1 is expressed
      in sporozoites and is lost after invasion of hepatocytes, and anti-AMA-1
      antibodies inhibit sporozoite invasion, suggesting that the protein is involved
      during invasion of hepatocytes. As observed with TRAP, AMA-1 is initially mostly
      sequestered within the sporozoite. Upon microneme exocytosis, AMA-1 and TRAP
      relocate to the sporozoite surface, where they are proteolytically cleaved,
      resulting in the shedding of soluble fragments. A subset of serine protease
      inhibitors blocks the processing and shedding of both AMA-1 and TRAP and inhibits
      sporozoite infectivity, suggesting that interfering with sporozoite proteolytic
      processing may constitute a valuable strategy to prevent hepatocyte infection.

PMID- 14676186
TI  - Stabilization of leukotriene A4 by epithelial fatty acid-binding protein in the
      rat basophilic leukemia cell.
AB  - Leukotriene A(4) (LTA(4)) is a chemically unstable triene epoxide product of 5
      lipoxygenase metabolism of arachidonic acid. Despite this chemical reactivity and
      its synthesis at the perinuclear membrane, LTA(4) is enzymatically converted into
      the cysteinyl leukotrienes and leukotriene B(4). Furthermore, LTA(4) participates
      in transcellular biosynthesis and is thus transferred between cells as an intact
      molecule. A cytosolic fatty acid-binding protein present in the rat basophilic
      leukemia cells was identified using mass spectrometry. This protein was
      determined to be the stabilizing factor present in the cell cytosol responsible
      for increasing the effective chemical half-life of LTA(4). Rat epithelial fatty
      acid-binding protein (E-FABP) was isolated using partial protein purification and
      immunoprecipitation. In-gel digestion with trypsin followed by peptide
      fingerprint analysis using matrix-assisted laser desorption ionization mass
      spectrometry and sequencing the major tryptic peptide obtained from liquid
      chromatography/mass spectrometry/mass spectrometry analysis identified E-FABP in
      the active fraction. Semi-quantitative Western blot analysis indicated that E
      FABP in the cytosolic fraction of RBL-1 cells was present at approximately 1-3
      pmol/10(6) cells. E-FABP (9 microm) was tested for its ability to stabilize
      LTA(4), and at 37 degrees C E-FABP was able to increase the half-life of LTA(4)
      from the previously reported half-life less than 3 s to a half-life of
      approximately 7 min. These results present a novel function for the well studied
      fatty acid-binding protein as a participant in leukotriene biosynthesis that
      permits LTA(4) to be available for further enzymatic processing in various
      cellular regions.

PMID- 14676187
TI  - Functional expression in Xenopus oocytes of gap-junctional hemichannels formed by
      a cysteine-less connexin 43.
AB  - Gap-junctional channels are formed by two connexons or gap-junctional
      hemichannels in series, with each connexon conformed by six connexin molecules.
      As with other membrane proteins, structural information on connexons can
      potentially be obtained with techniques that take advantage of the highly
      specific thiol chemistry by positioning Cys residues at locations of interest,
      ideally in an otherwise Cys-less protein. It has been shown that conserved Cys
      residues located in the extracellular loops of connexins are essential for the
      docking of connexons from adjacent cells, preventing the formation of functional
      gap-junctional channels. Here we engineered a Cys-less version of connexin 43
      (Cx43) and assessed its function using a Xenopus oocyte expression system. The
      Cys-less protein was expressed at the plasma membrane and did not form gap
      junctional channels but formed hemichannels that behave similarly to those formed
      by Cx43 in terms of permeation to carboxyfluorescein. The carboxyfluorescein
      permeability of Cys-less hemichannels was increased by protein kinase C
      inhibition, like the wild-type Cx43 hemichannels. We generated a protein with a
      single Cys in a position (residue 34) thought to face the channel pore and show
      that thiol modification of the Cys abolishes the carboxyfluorescein permeability.
      We conclude that Cysless Cx43 forms regulated functional hemichannels, and
      therefore Cys-less Cx43 is a useful tool for future structural studies.

PMID- 14676188
TI  - The C-terminal sequence of LMADS1 is essential for the formation of homodimers
      for B function proteins.
AB  - LMADS1, a lily (Lilium longiflorum) AP3 orthologue, contains the complete
      consensus sequence of the paleoAP3 (YGSHDLRLA) and PI-derived (YEFRVQPSQPNLH)
      motifs in the C-terminal region of the protein. Interestingly, through yeast two
      hybrid analysis, LMADS1 was found to be capable of forming homodimers. These
      results indicated that LMADS1 represents an ancestral form of the B function
      protein, which retains the ability to form homodimers in regulating petal and
      stamen development in lily. To explore the involvement of the conserved motifs in
      the C-terminal region of LMADS1 in forming homodimers, truncated forms of LMADS1
      were generated, and their ability to form homodimers was analyzed using yeast two
      hybrid and electrophoretic mobility shift assay. The ability of LMADS1 to form
      homodimers decreased once the C-terminal paleoAP3 motif was deleted. When both
      paleoAP3 and PI-derived motifs were deleted, the ability of LMADS1 to form
      homodimers was completely abolished. This result indicated that although the
      paleoAP3 motif promotes the formation of LMADS1 homodimers, the PI-derived motif
      is essential. Deletion analysis indicated that two amino acids, RV, of the 5
      final amino acids, YEFRV, in the PI-derived motif are essential for the formation
      of homodimers. Further, point mutation analysis indicated that amino acid Val was
      absolutely necessary, whereas residue Arg played a less important role in the
      formation of homodimers. Furthermore, Arabidopsis AP3 was able to form homodimers
      once its C-terminal region was replaced by that of LMADS1. This result indicated
      that the C-terminal region of LMADS1 is responsible and essential for homodimer
      formation of the ancestral form of the B function protein.

PMID- 14676189
TI  - Activation of Raf/MEK/ERK/cPLA2 signaling pathway is essential for chlamydial
      acquisition of host glycerophospholipids.
AB  - Chlamydiae, a diverse group of obligate intracellular pathogens replicating
      within cytoplasmic vacuoles of eukaryotic cells, are able to acquire lipids from
      host cells. Here we report that activation of the host Raf-MEK-ERK-cPLA2
      signaling cascade is required for the chlamydial uptake of host
      glycerophospholipids. Both the MAP kinase pathway (Ras/Raf/MEK/ERK) and Ca(2+)
      dependent cytosolic phospholipase A2 (cPLA2) were activated in chlamydia-infected
      cells. The inhibition of cPLA2 activity resulted in the blockade of the
      chlamydial uptake of host glycerophospholipids and impairment in chlamydial
      growth. Blocking either c-Raf-1 or MEK1/2 activity prevented the chlamydial
      activation of ERK1/2, leading to the suppression of both chlamydial activation of
      the host cPLA2 and uptake of glycerophospholipids from the host cells. The
      chlamydia-induced phosphorylation of cPLA2 was also blocked by a dominant
      negative ERK2. Furthermore, activation of both ERK1/2 and cPLA2 was dependent on
      chlamydial growth and restricted within chlamydia-infected cells, suggesting an
      active manipulation of the host ERK-cPLA2 signaling pathway by chlamydiae.

PMID- 14676190
TI  - Glycosylphosphatidylinositol-anchored proteins and actin cytoskeleton modulate
      chloride transport by channels formed by the Helicobacter pylori vacuolating
      cytotoxin VacA in HeLa cells.
AB  - The vacuolating cytotoxin VacA is an important virulence factor of Helicobacter
      pylori. Removing glycosylphosphatidylinositol-anchored proteins (GPI-Ps) from the
      cell surface by phosphatidylinositol-phospholipase C or disrupting the cell actin
      cytoskeleton by cytochalasin D reduced VacA-induced vacuolation of cells. Using
      the fluorescent dye 6-methoxy-N-ethylquinolinium chloride, an indicator for
      cytosolic chloride, we have investigated the role of either GPI-Ps or actin
      cytoskeleton in the activity of the selective anionic channel formed by VacA at
      the plasma membrane level. Removal of GPI-Ps from HeLa cell surfaces did not
      impair VacA localization into lipid rafts but strongly reduced VacA channel
      mediated cell influx and efflux of chloride. Disruption of the actin cytoskeleton
      of HeLa cells by cytochalasin D did not affect VacA localization in lipid rafts
      but blocked VacA cell internalization and inhibited cell vacuolation while
      increasing the overall chloride transport by the toxin channel at the cell
      surface. Specific enlargement of Rab7-positive compartments induced by VacA could
      be mimicked by the weak base chloroquine alone, and the vacuolating activities of
      either chloroquine alone or VacA were blocked with the same potency by the anion
      channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoic acid shown to inhibit
      VacA channel activity. We suggest that formation of functional VacA channels at
      the cell surface required GPI-Ps and that endocytosis of these channels by an
      actin-dependent process increases the chloride content of late endosomes that
      accumulate weak bases, provoking their enlargement by osmotic swelling.

PMID- 14676191
TI  - Comprehensive proteomic analysis of human Par protein complexes reveals an
      interconnected protein network.
AB  - The polarization of eukaryotic cells is controlled by the concerted activities of
      asymmetrically localized proteins. The PAR proteins, first identified in
      Caenorhabditis elegans, are common regulators of cell polarity conserved from
      nematode and flies to man. However, little is known about the molecular
      mechanisms by which these proteins and protein complexes establish cell polarity
      in mammals. We have mapped multiprotein complexes formed around the putative
      human Par orthologs MARK4 (microtubule-associated protein/microtubule affinity
      regulating kinase 4) (Par-1), Par-3, LKB1 (Par-4), 14-3-3zeta and eta (Par-5),
      Par-6a, -b, -c, and PKClambda (PKC3). We employed a proteomic approach comprising
      tandem affinity purification (TAP) of protein complexes from cultured cells and
      protein sequencing by tandem mass spectrometry. From these data we constructed a
      highly interconnected protein network consisting of three core complex "modules"
      formed around MARK4 (Par-1), Par-3.Par-6, and LKB1 (Par-4). The network confirms
      most previously reported interactions. In addition we identified more than 50
      novel interactors, some of which, like the 14-3-3 phospho-protein scaffolds,
      occur in more than one distinct complex. We demonstrate that the complex
      formation between LKB1.Par-4, PAPK, and Mo25 results in the translocation of LKB1
      from the nucleus to the cytoplasm and to tight junctions and show that the LKB1
      complex may activate MARKs, which are known to introduce 14-3-3 binding sites
      into several substrates. Our findings suggest co-regulation and/or signaling
      events between the distinct Par complexes and provide a basis for further
      elucidation of the molecular mechanisms that govern cell polarity.

PMID- 14676192
TI  - Hypoxia selection of death-resistant cells. A role for Bcl-X(L).
AB  - Under hypoxia, some cells are irreversibly injured and die, whereas others can
      adapt to the stress and survive. The molecular and genetic basis underlying
      cellular sensitivity to hypoxic injury is unclear. Here we have selected death
      resistant cells by repeated episodes of hypoxia. The selected cells are cross
      resistant to apoptosis induced by staurosporine, azide, and cisplatin. These
      cells up-regulate Bcl-X(L), an anti-apoptotic protein. Bcl-X(L) interacts with
      the pro-apoptotic molecule Bax and abrogates its toxicity in mitochondria,
      resulting in the preservation of mitochondrial integrity, cytochrome c, and cell
      viability. Down-regulation of Bcl-X(L) by antisense oligonucleotides or the newly
      identified Bcl-X(L) inhibitor chelerythrine restores cellular sensitivity to
      injury and death. Thus, Bcl-X(L) is a key molecule for hypoxia selection of death
      resistance. These findings may have important implications for the development of
      solid tumors where hypoxia selects for death-resistant cells that are inert to
      cancer therapy.

PMID- 14676193
TI  - Functional role of the lock and key motif at the subunit interface of glutathione
      transferase p1-1.
AB  - The glutathione transferases (GSTs) represent a superfamily of dimeric proteins.
      Each subunit has an active site, but there is no evidence for the existence of
      catalytically active monomers. The lock and key motif is responsible for a highly
      conserved hydrophobic interaction in the subunit interface of pi, mu, and alpha
      class glutathione transferases. The key residue, which is either Phe or Tyr
      (Tyr(50) in human GSTP1-1) in one subunit, is wedged into a hydrophobic pocket of
      the other subunit. To study how an essentially inactive subunit influences the
      activity of the neighboring subunit, we have generated the heterodimer composed
      of subunits from the fully active human wild-type GSTP1-1 and the nearly inactive
      mutant Y50A obtained by mutation of the key residue Tyr(50) to Ala. Although the
      key residue is located far from the catalytic center, the k(cat) value of mutant
      Y50A decreased about 1300-fold in comparison with the wild-type enzyme. The
      decrease of the k(cat) value of the heterodimer by about 27-fold rather than the
      expected 2-fold in comparison with the wild-type enzyme indicates that the two
      active sites of the dimeric enzyme work synergistically. Further evidence for
      cooperativity was found in the nonhyperbolic GSH saturation curves. A network of
      hydrogen-bonded water molecules, found in crystal structures of GSTP1-1, connects
      the two active sites and the main chain carbonyl group of Tyr(50), thereby
      offering a mechanism for communication between the two active sites. It is
      concluded that a subunit becomes catalytically competent by positioning the key
      residue of one subunit into the lock pocket of the other subunit, thereby
      stabilizing the loop following the helix alpha2, which interacts directly with
      GSH.

PMID- 14676194
TI  - Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell
      adhesion.
AB  - Mesothelin is a glycosylphosphatidylinositol-linked cell surface molecule
      expressed in the mesothelial lining of the body cavities and in many tumor cells.
      Based on the finding that a soluble form of mesothelin specifically binds to
      ovarian carcinoma cell line OVCAR-3, we isolated cDNAs encoding a mesothelin
      binding protein by expression cloning. The polypeptides encoded by the two cloned
      cDNA fragments matched to portions of CA125, an ovarian cancer antigen and a
      giant mucin-like glycoprotein present at the surface of tumor cells. By flow
      cytometric analysis and immunoprecipitation, we demonstrate that CA125 binds to
      mesothelin in a specific manner. Binding of CA125 to membrane-bound mesothelin
      mediates heterotypic cell adhesion as anti-mesothelin antibody blocks binding of
      OVCAR-3 cells expressing CA125 to an endothelial-like cell line expressing
      mesothelin. Finally, we show that CA125 and mesothelin are co-expressed in
      advanced grade ovarian adenocarcinoma. Taken together, our data indicate that
      mesothelin is a novel CA125-binding protein and that CA125 might contribute to
      the metastasis of ovarian cancer to the peritoneum by initiating cell attachment
      to the mesothelial epithelium via binding to mesothelin.

PMID- 14676195
TI  - Escherichia coli periplasmic thiol peroxidase acts as lipid hydroperoxide
      peroxidase and the principal antioxidative function during anaerobic growth.
AB  - To clarify the enzymatic property of Escherichia coli periplasmic thiol
      peroxidase (p20), the specific peroxidase activity toward peroxides was compared
      with other bacterial thiol peroxidases. p20 has the most substrate preference and
      peroxidase activity toward organic hydroperoxide. Furthermore, p20 exerted the
      most potent lipid peroxidase activity. Despite that the mutation of p20 caused
      the highest susceptibility toward organic hydroperoxide and heat stress, the
      cellular level of p20 did not respond to the exposure of oxidative stress.
      Expression level of p20 during anaerobic growth was sustained at the
      approximately 50% level compared with that of the aerobic growth. Viability of
      aerobic p20Delta without glucose was reduced to the approximately 65% level of
      isogenic strains, whereas viability of aerobic p20Delta with 0.5% glucose
      supplement was sustained. The deletion of p20 resulted in a gradual loss of the
      cell viability during anaerobic growth. At the stationary phase, the viability of
      p20Delta was down to approximately 10% level of parent strains. An analysis of
      the protein carbonyl contents of p20Delta as a marker for cellular oxidation
      indicates that severe reduction of viability of anaerobic p20Delta was caused by
      cumulative oxidative stress. P20Delta showed hypersensitivity toward membrane
      soluble organic hydroperoxides. An analysis of protein carbonyl and lipid
      hydroperoxide contents in the membrane of the stress-imposed p20Delta
      demonstrates that the severe reduction of viability was caused by cumulative
      oxidative stress on the membrane. Taken together, present data uncover in vivo
      function for p20 as a lipid hydroperoxide peroxidase and demonstrate that, as the
      result, p20 acts as the principal antioxidant in the anaerobic habitats.

PMID- 14676196
TI  - Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral
      fatty acid binding site.
AB  - A 2.7-Angstrom molecular structure of human microsomal cytochrome P450 2C8
      (CYP2C8) was determined by x-ray crystallography. The membrane protein was
      modified for crystallization by replacement of the hydrophobic N-terminal
      transmembrane domain with a short hydrophilic sequence before residue 28. The
      structure of the native sequence is complete from residue 28 to the beginning of
      a C-terminal histidine tag used for purification. CYP2C8 is one of the principal
      hepatic drug-metabolizing enzymes that oxidizes therapeutic drugs such as taxol
      and cerivastatin and endobiotics such as retinoic acid and arachidonic acid.
      Consistent with the relatively large size of its preferred substrates, the active
      site volume is twice that observed for the structure of CYP2C5. The extended
      active site cavity is bounded by the beta1 sheet and helix F' that have not
      previously been implicated in substrate recognition by mammalian P450s. CYP2C8
      crystallized as a symmetric dimer formed by the interaction of helices F, F', G',
      and G. Two molecules of palmitic acid are bound in the dimer interface. The dimer
      is observed in solution, and mass spectrometry confirmed the association of
      palmitic acid with the enzyme. This novel finding identifies a peripheral binding
      site in P450s that may contribute to drug-drug interactions in P450 metabolism.

PMID- 14676197
TI  - CD40/CD40 homodimers are required for CD40-induced phosphatidylinositol 3-kinase
      dependent expression of B7.2 by human B lymphocytes.
AB  - Preformed CD40/CD40 homodimers were initially observed on human Burkitt lymphoma
      cell lines, normal B cells, and transitional bladder carcinoma cell lines.
      However, the nature and the biological relevance of these homodimers have not yet
      been investigated. In the present study, we demonstrated that Epstein-Barr virus
      transformed B cells and CD40-transfected HEK 293 cells constitutively expressed
      disulfide-linked CD40/CD40 homodimers at low levels. Oligomerization of CD40
      leads to a rapid and significant increase in the disulfide-linked CD40/CD40
      homodimer formation, a response that could be prevented using a thiol-alkylating
      agent. Formation of CD40/CD40 homodimers was found to be absolutely required for
      CD40-mediated activation of phosphatidylinositol 3-kinase, which, in turn
      regulated B7.2 expression. In contrast, CD40 monomers provided the minimal signal
      emerging from CD40, activating p38 MAP kinase and inducing homotypic B cell
      adhesion. CD40/CD40 homodimer formation was totally independent of TRAF1/2/3/5
      associations with the threonine at position 254 in the cytoplasmic tail of the
      CD40 molecules. This finding may be vital to better understanding the molecular
      mechanisms that govern cell signaling triggered by CD40/CD154 interactions.

PMID- 14676198
TI  - Focal adhesion kinase regulation of N-WASP subcellular localization and function.
AB  - N-WASP is a member of the WASP family of proteins that regulate actin
      cytoskeleton remodeling. FAK is a cytoplasmic tyrosine kinase implicated in
      integrin signaling during cell migration. Here we identify a direct interaction
      between N-WASP and FAK and show that N-WASP is phosphorylated by FAK at a
      conserved tyrosine residue, Tyr(256). We found that phosphorylation of Tyr(256)
      affected N-WASP nuclear localization, suggesting that phosphorylation of N-WASP
      by FAK may regulate its activity in vivo by altering its subcellular
      localization. We also showed that the nuclear localization of N-WASP is dependent
      on its being in the open conformation either after its activation by Cdc42 or the
      truncation of the C-terminal VCA domain. Phosphorylation of Tyr(256) of N-WASP
      could reduce its interaction with nuclear importin NPI-1, which might be
      responsible for its decreased nuclear localization. Lastly, we show that
      phosphorylation of Tyr(256) plays an important role in promoting cell migration.
      Together, these results suggest a novel regulatory mechanism of N-WASP by
      tyrosine phosphorylation and subcellular localization and its potential role in
      the regulation of cell migration.

PMID- 14676199
TI  - Differential export requirements for shuttling serine/arginine-type mRNA-binding
      proteins.
AB  - Messenger RNAs are transported to the cytoplasm bound to several shuttling mRNA
      binding proteins. Here, we present the characterization of Hrb1, a novel
      component of the transported ribonucleoprotein complex in Saccharomyces
      cerevisiae. The protein is similar to the other two serine/arginine (SR)-type
      proteins in yeast, Gbp2 and Npl3. Hrb1 is nuclear at steady state and its import
      is mediated by the karyopherin Mtr10. Hrb1 binds to poly(A)+ RNA in vivo and its
      binding is significantly increased in MTR10 mutants, suggesting a role for Mtr10
      in dissociating Hrb1 from the mRNAs. Interestingly, by comparing the export
      requirements of all three SR proteins we find similarities but also striking
      differences. While the export of all three proteins is dependent on the export of
      mRNAs in general, as no transport is observed in mutants defective in
      transcription (rpb1-1) or mRNA export (mex67-5), we find specific requirements
      for components of the THO complex, involved in transcription elongation. While
      both Hrb1 and Gbp2 depend on Mft1 and Hpr1 for their nuclear export, Npl3 is
      exported independently of both proteins. These findings suggest that Hrb1 and
      Gbp2, but not Npl3, might be loaded onto the growing mRNA via the THO complex
      components Mtf1 and Hrp1.

PMID- 14676200
TI  - Phosphorylation of conserved casein kinase sites regulates cAMP-response element
      binding protein DNA binding in Drosophila.
AB  - The Drosophila homolog of cAMP-response element-binding protein (CREB), dCREB2,
      exists with serine 231, equivalent to mammalian serine 133, in a predominantly
      phosphorylated state. Thus, unlike the mammalian protein, the primary regulation
      of dCREB2 may occur at a different step from serine 231 phosphorylation. Although
      bacterially expressed dCREB2 bound cAMP-response element sites, protein from
      Drosophila extracts was unable to do so unless treated with phosphatase.
      Phosphorylation of recombinant protein by casein kinase (CK) I or II, but not
      calcium-calmodulin kinase II or protein kinase A, inhibited DNA binding. Up to
      four conserved CK sites likely to be phosphorylated in vivo were responsible for
      this effect, and these sites were phosphorylated by a kinase present in
      Drosophila cell extracts that biochemically resembles CKII. We propose that the
      relative importance of different signaling pathways in regulating CREB activity
      may differ between Drosophila and mammals. In Drosophila, the dephosphorylation
      of CK sites appears to be the major regulatory step, while phosphorylation of
      serine 231 is necessary but secondary.

PMID- 14676201
TI  - 12/15-Lipoxygenase activity mediates inflammatory monocyte/endothelial
      interactions and atherosclerosis in vivo.
AB  - We have shown that the 12/15-lipoxygenase (12/15-LO) product 12S
      hydroxyeicosatetraenoic acid increases monocyte adhesion to human endothelial
      cells (EC) in vitro. Recent studies have implicated 12/15-LO in mediating
      atherosclerosis in mice. We generated transgenic mice on a C57BL/6J (B6)
      background that modestly overexpressed the murine 12/15-LO gene (designated
      LOTG). LOTG mice had 2.5-fold elevations in levels of 12S-hydroxyeicosatetraenoic
      acid and a 2-fold increase in expression of 12/15-LO protein in vivo. These mice
      developed spontaneous aortic fatty streak lesions on a chow diet. Thus, we
      examined effects of 12/15-LO expression on early events leading to
      atherosclerosis in these mice. We found that, under basal unstimulated
      conditions, LOTG EC bound more monocytes than B6 control EC (18 +/- 2 versus 7 +/
      1 monocytes/field, respectively; p < 0.0001). Inhibition of 12/15-LO activity in
      LOTG EC using a 12/15-LO ribozyme completely blocked monocyte adhesion in LOTG
      mice. Thus, 12/15-LO activity is required for monocyte/EC adhesion in the vessel
      wall. Expression of ICAM-1 in aortic endothelia of LOTG mice was increased
      severalfold. VCAM-1 expression was not changed. In a series of blocking studies,
      antibodies to alpha(4) and beta(2) integrins in WEHI monocytes blocked monocyte
      adhesion to both LOTG and B6 control EC. Inhibition of ICAM-1, VCAM-1, and
      connecting segment-1 fibronectin in EC significantly reduced adhesion of WEHI
      monocytes to LOTG EC. In summary, these data indicate that EC from LOTG mice are
      "pre-activated" to bind monocytes. Monocyte adhesion in LOTG mice is mediated
      through beta(2) integrin and ICAM-1 interactions as well as through VLA-4 and
      connecting segment-1 fibronectin/VCAM-1 interactions. Thus, 12/15-LO mediates
      monocyte/EC interactions in the vessel wall in atherogenesis at least in part
      through molecular regulation of expression of endothelial adhesion molecules.

PMID- 14676202
TI  - Differential effect of transforming growth factor beta (TGF-beta) on the genes
      encoding hyaluronan synthases and utilization of the p38 MAPK pathway in TGF-beta
      induced hyaluronan synthase 1 activation.
AB  - Unfettered hyaluronan (HA) production is a hallmark of rheumatoid arthritis. The
      discovery of three genes encoding hyaluronan synthases (HASs) allows for the
      investigation of the signaling pathways leading to the activation of these genes.
      Our objective is to further understanding of the regulation of these genes as
      well as to find ways to prevent undesired gene activation. Human fibroblast-like
      synoviocytes were used in these experiments. mRNA levels of HAS were monitored by
      reverse transcriptase-PCR. A series of specific kinase inhibitors were used to
      investigate intracellular pathways leading to the up-regulation of HAS1. Our
      experiments, testing a series of stimuli including tumor necrosis factor alpha
      (TNFalpha), demonstrate that TGF-beta is the most potent stimulus for HAS1
      transcription. TGF-beta activates HAS1 in a dose-dependent manner with a maximum
      effect at a concentration of 0.5-1 ng/ml. TGF-beta-induced HAS1 mRNA can be
      detected within 60 min and reaches maximal levels at 6 h. Furthermore, TGF-beta
      treatment leads to an increase in synthase activity as determined by HA ELISA and
      by in vitro HA synthase assays. In contrast to the activatory effect on HAS1, TGF
      beta dose-dependently suppresses HAS3 mRNA. As to the mode of action of TGF-beta
      induced HAS1 mRNA activation, our experiments reveal that blocking p38 MAPK
      inhibited the TGF-beta effect by 90%, blocking the MEK pathway led to an
      inhibition by 40%, and blocking the JNK pathway had no effect. The presented data
      might contribute to a better understanding of the role of TGF-beta and of HA in
      the pathology of diseases.

PMID- 14676203
TI  - Identification and relevance of the CD95-binding domain in the N-terminal region
      of ezrin.
AB  - The CD95 (Fas/APO-1) linkage to the actin cytoskeleton through ezrin is an
      essential requirement for susceptibility to the CD95-mediated apoptosis in CD4+ T
      cells. We have previously shown that moesin was not involved in the binding to
      CD95. Here we further support the specificity of the ezrin/CD95 binding, showing
      that radixin did not bind CD95. The ezrin region specifically and directly
      involved in the binding to CD95 was located in the middle lobe of the ezrin FERM
      domain, between amino acids 149 and 168. In this region, ezrin, radixin, and
      moesin show 60-65% identity, as compared with the 86% identity in the whole FERM
      domain. Transfection of two different human cell lines with a green fluorescent
      protein-tagged ezrin mutated in the CD95-binding epitope, induced a marked
      inhibition of CD95-mediated apoptosis. In these cells, the mutated ezrin did not
      co-localize or co-immunoprecipitate with CD95. Further analysis showed that the
      mutated ezrin, while unable to bind CD95, was fully able to bind actin, thus
      preventing the actin linkage to CD95. Altogether, our results support the
      specificity of ezrin in the association to CD95 and the importance of the ezrin
      to-CD95 linkage in CD95-mediated apoptosis. Moreover, this study suggests that a
      major role of ezrin is to connect CD95 to actin, thus allowing the CD95
      polarization on the cells and the occurrence of the following multiple cascades
      of the CD95 pathway.

PMID- 14676205
TI  - EHD2 and the novel EH domain binding protein EHBP1 couple endocytosis to the
      actin cytoskeleton.
AB  - Here we identified two novel proteins denoted EH domain protein 2 (EHD2) and EHD2
      binding protein 1 (EHBP1) that link clathrin-mediated endocytosis to the actin
      cytoskeleton. EHD2 contains an N-terminal P-loop and a C-terminal EH domain that
      interacts with NPF repeats in EHBP1. Disruption of EHD2 or EHBP1 function by
      small interfering RNA-mediated gene silencing inhibits endocytosis of transferrin
      into EEA1-positive endosomes as well as GLUT4 endocytosis into cultured
      adipocytes. EHD2 localizes with cortical actin filaments, whereas EHBP1 contains
      a putative actin-binding calponin homology domain. High expression of EHD2 or
      EHBP1 in intact cells mediates extensive actin reorganization. Thus EHD2 appears
      to connect endocytosis to the actin cytoskeleton through interactions of its N
      terminal domain with membranes and its C-terminal EH domain with the novel EHBP1
      protein.

PMID- 14676204
TI  - A single amino acid residue defines the difference in ovalicin sensitivity
      between type I and II methionine aminopeptidases.
AB  - TNP-470, the first anti-angiogenic small molecule to enter clinical trials,
      targets methionine aminopeptidase-2 (MetAP-2), a metalloprotease that cleaves the
      N-terminal methionine of proteins. Previously, biochemical binding, in vivo yeast
      studies, and structural studies of human methionine aminopeptidase-2 bound to TNP
      470 and its analogs fumagillin and ovalicin revealed that these compounds exhibit
      specificity for MetAP-2 over its family member MetAP-1. To further elucidate the
      nature of this specificity, we developed a yeast-based screen for human MetAP-2
      mutations that confer ovalicin resistance. Of the three resistant alleles, A362T
      appeared in the majority of clones and was found to be the most resistant to the
      ovalicin class of inhibitors. Alignment of human MetAP-2 with human MetAP-1,
      which is naturally ovalicin-resistant, revealed that the analogous residue in
      MetAP-1 is also a threonine. Mutation of this residue to alanine resulted in an
      ovalicin-sensitive MetAP-1 allele, demonstrating that an alanine at this position
      is critical for inhibition by ovalicin. These results provide a molecular
      explanation for the specificity exhibited by this class of anti-angiogenic agents
      for MetAP-2 over MetAP-1 and may prove useful in the development of additional
      MetAP-2-specific therapeutic agents.

PMID- 14676206
TI  - Anthracyclines induce calpain-dependent titin proteolysis and necrosis in
      cardiomyocytes.
AB  - Titin, the largest myofilament protein, serves as a template for sarcomere
      assembly and acts as a molecular spring to contribute to diastolic function.
      Titin is known to be extremely susceptible to calcium-dependent protease
      degradation in vitro. We hypothesized that titin degradation is an early event in
      doxorubicin-induced cardiac injury and that titin degradation occurs by
      activation of the calcium-dependent proteases, the calpains. Treatment of
      cultured adult rat cardiomyocytes with 1 or 3 micromol/liter doxorubicin for 24 h
      resulted in degradation of titin in myocyte lysates, which was confirmed by a
      reduction in immunostaining of an antibody to the spring-like (PEVK) domain of
      titin at the I-band of the sarcomere. The elastic domain of titin appears to be
      most susceptible to proteolysis because co-immunostaining with an antibody to
      titin at the M-line was preserved, suggesting targeted proteolysis of the spring
      like domain of titin. Doxorubicin treatment for 1 h resulted in approximately 3
      fold increase in calpain activity, which remained elevated at 48 h. Co-treatment
      with calpain inhibitors resulted in preservation of titin, reduction in
      myofibrillar disarray, and attenuation of cardiomyocyte necrosis but not
      apoptosis. Co-treatment with a caspase inhibitor did not prevent the degradation
      of titin, which precludes caspase-3 as an early mechanism of titin proteolysis.
      We conclude that calpain activation is an early event after doxorubicin treatment
      in cardiomyocytes and appears to target the degradation of titin. Proteolysis of
      the spring-like domain of titin may predispose cardiomyocytes to diastolic
      dysfunction, myofilament instability, and cell death by necrosis.

PMID- 14676207
TI  - Differential phosphorylation of c-Jun and JunD in response to the epidermal
      growth factor is determined by the structure of MAPK targeting sequences.
AB  - MAPK phosphorylation of various substrates is mediated by the presence of docking
      sites, including the D domain and the DEF motif. Depending on the number and
      sequences of these domains, substrates are phosphorylated by specific subsets of
      MAPKs. For example, a D domain targets JNK to c-Jun, whereas a DEF motif is
      required for ERK phosphorylation of c-Fos. JunD, in contrast, contains both D and
      DEF domains. Here we show that these motifs mediate JunD phosphorylation in
      response to either ERK or JNK activation. An intact D domain is required for
      phosphorylation and activation of JunD by both subtypes of MAPK. The DEF motif
      acts together with the D domain to elicit efficient phosphorylation of JunD in
      response to the epidermal growth factor (EGF) but has no function on JunD
      phosphorylation and activation by JNK signaling. Furthermore, we show that
      conversion of a c-Jun sequence to a canonical DEF domain, as it is present in
      JunD, elicits c-Jun activation in response to EGF. Our results suggest that
      evolution of a particular modular system of MAPK targeting sequences has
      determined a differential response of JunD and c-Jun to ERK activation.

PMID- 14676208
TI  - Site of docking and fusion of insulin secretory granules in live MIN6 beta cells
      analyzed by TAT-conjugated anti-syntaxin 1 antibody and total internal reflection
      fluorescence microscopy.
AB  - To determine the site of insulin exocytosis in the pancreatic beta cell plasma
      membrane, we analyzed the interaction between the docking/fusion of green
      fluorescent protein-tagged insulin granules and syntaxin 1 labeled by TAT
      conjugated Cy3-labeled antibody (Ab) using total internal reflection fluorescence
      microscopy (TIRFM). Monoclonal Ab against syntaxin 1 was labeled with Cy3 then
      conjugated with the protein transduction domain of HIV-1 TAT. TAT-conjugated Cy3
      labeled anti-syntaxin 1 Ab was transduced rapidly into the subplasmalemmal region
      in live MIN6 beta cells, which enabled us to observe the spatial organization and
      distribution of endogenous syntaxin 1. TIRFM imaging revealed that syntaxin 1 is
      distributed in numerous separate clusters in the intact plasma membrane, where
      insulin secretory granules were docked preferentially to the sites of syntaxin 1
      clusters, colocalizing with synaptosomal-associated protein of 25 kDa (SNAP-25)
      clusters. TIRFM imaging analysis of the motion of single insulin granules
      demonstrated that the fusion of insulin secretory granules stimulated by 50 mm
      KCl occurred exclusively at the sites of the syntaxin 1 clusters. Cholesterol
      depletion by methyl-beta-cyclodextrin treatment, in which the syntaxin 1 clusters
      were disintegrated, decreased the number of docked insulin granules, and,
      eventually the number of fusion events was significantly reduced. Our results
      indicate that 1) insulin exocytosis occurs at the site of syntaxin 1 clusters; 2)
      syntaxin 1 clusters are essential for the docking and fusion of insulin granules
      in MIN6 beta cells; and 3) the sites of syntaxin 1 clusters are distinct from
      flotillin-1 lipid rafts.

PMID- 14676209
TI  - Transforming growth factor-beta1-dependent urokinase up-regulation and promotion
      of invasion are involved in Src-MAPK-dependent signaling in human ovarian cancer
      cells.
AB  - Urokinase-type plasminogen activator (uPA) has been implicated in tumor cell
      invasion and metastasis. We reported previously that transforming growth factor
      (TGF)-beta1 induces a dose- and time-dependent up-regulation of uPA mRNA and
      protein in highly invasive human ovarian cancer cell line HRA, leading to
      invasion. To further elucidate the mechanism of the invasive effect of TGF-beta1,
      we investigated which signaling pathway transduced by TGF-beta1 is responsible
      for this effect. Here, we show that 1) nontoxic concentrations of TGF-beta1
      activated Src kinase; 2) TGF-beta1 rapidly phosphorylates ERK1/2 and Akt, but not
      p38; 3) pharmacological Src inhibitor PP2 or antisense (AS) c-Src
      oligodeoxynucleotide (ODN) treatment reduced TGF-beta1-induced phosphorylation of
      ERK1/2 and Akt by 85-90% compared with controls; 4) pharmacological inhibition of
      MAPK by PD98059 abrogated TGF-beta1-mediated Akt stimulation, whereas TGF-beta1
      induced ERK1/2 stimulation was not inhibited by PI3K inhibitor LY294002 or AS
      PI3K ODN transfection; 5) up-regulation of uPA mRNA in response to TGF-beta1 was
      almost totally blocked by PP2 and PD98059 and partially ( approximately 55%) by
      LY294002; 6) TGF-beta1-induced uPA mRNA up-regulation was inhibited by treatment
      with AS ODNs to c-Src or PI3K by 90 or 60%, respectively, compared with control
      ODN treatment; and 7) blockade of the release of the transcription factor NF
      kappaB by pyrrolidinedithiocarbamate reduced the TGF-beta1-induced activation of
      the uPA gene by approximately 65%. In addition, curcumin, a blocker of the
      transcriptional factor AP-1, partially (35%) canceled this effect. Taken
      together, these data support a role for TGF-beta1 activation of two distinct
      pathways (Src-MAPK-PI3K-NF-kappaB-dependent and Src-MAPK-AP-1-dependent) for TGF
      beta1-dependent uPA up-regulation and promotion of invasion.

PMID- 14676210
TI  - Ceramide 1-phosphate is a direct activator of cytosolic phospholipase A2.
AB  - Recently, we demonstrated that ceramide kinase, and its product, ceramide 1
      phosphate (Cer-1-P), were mediators of arachidonic acid released in cells in
      response to interleukin-1beta and calcium ionophore (Pettus, B. J., Bielawska,
      A., Spiegel, S., Roddy, P., Hannun, Y. A., and Chalfant, C. E. (2003) J. Biol.
      Chem. 278, 38206-38213). In this study, we demonstrate that down-regulation of
      cytosolic phospholipase A(2) (cPLA(2)) using RNA interference technology
      abolished the ability of Cer-1-P to induce arachidonic acid release in A549
      cells, demonstrating that cPLA(2) is the key phospholipase A(2) downstream of Cer
      1-P. Treatment of A549 cells with Cer-1-P (2.5 microm) induced the translocation
      of full-length cPLA(2) from the cytosol to the Golgi apparatus/perinuclear
      regions, which are known sites of translocation in response to agonists. Cer-1-P
      also induced the translocation of the CaLB/C2 domain of cPLA(2) in the same
      manner, suggesting that this domain is responsive to Cer-1-P either directly or
      indirectly. In vitro studies were then conducted to distinguish these two
      possibilities. In vitro binding studies disclosed that Cer-1-P interacts directly
      with full-length cPLA(2) and with the CaLB domain in a calcium- and lipid
      specific manner with a K(Ca) of 1.54 microm. Furthermore, Cer-1-P induced a
      calcium-dependent increase in cPLA(2) enzymatic activity as well as lowering the
      EC(50) of calcium for the enzyme from 191 to 31 nm. This study identifies Cer-1-P
      as an anionic lipid that translocates and directly activates cPLA(2),
      demonstrating a role for this bioactive lipid in the mediation of inflammatory
      responses.

PMID- 14676211
TI  - Catalytic activity of human ADAM33.
AB  - ADAM33 (a disintegrin and metalloproteinase) is an asthma susceptibility gene
      recently identified through a genetic study of asthmatic families (van Eerdewegh
      et al. (2002) Nature 418, 426-430). In order to characterize the catalytic
      properties of ADAM33, the metalloproteinase domain of human ADAM33 was expressed
      in Drosophila S2 cells and purified. The N-terminal sequence of the purified
      metalloproteinase was exclusively (204)EARR, indicating utilization of one of
      three furin recognition sites. Of many synthetic peptides tested as potential
      substrates, four peptides derived from beta-amyloid precursor protein (APP), Kit
      ligand-1 (KL-1), tumor necrosis factor-related activation-induced cytokine, and
      insulin B chain were cleaved by ADAM33; mutation at the catalytic site, E346A,
      inactivated catalytic activity. Cleavage of APP occurred at His(14)/Gln(15), not
      at the alpha-secretase site and was inefficient (k(cat)/K(m) (1.6 +/- 0.3) x
      10(2) m(-1) s(-1)). Cleavage of a juxtamembrane KL-1 peptide occurred at a site
      used physiologically with a similar efficiency. Mutagenesis of KL-1 peptide
      substrate indicated that the P3, P2, P1, and P3' residues were critical for
      activity. In a transfected cell-based sheddase assay, ADAM33 functioned as a
      negative regulator of APP shedding and mediated some constitutive shedding of KL
      1, which was not regulated by phorbol 12-myristate 13-acetate activation. ADAM33
      activity was sensitive to several hydroxamate inhibitors (IK682, K(i) = 23 +/- 7
      nm) and to tissue inhibitors of metalloproteinase (TIMPs). Activity was inhibited
      moderately by TIMP-3 and TIMP-4 and weakly inhibited by TIMP-2 but not by TIMP-1,
      a profile distinct from other ADAMs. The identification of ADAM33 peptide
      substrates, cellular activity, and a distinct inhibitor profile provide the basis
      for further functional studies of ADAM33.

PMID- 14676212
TI  - UTP transactivates epidermal growth factor receptors and promotes cardiomyocyte
      hypertrophy despite inhibiting transcription of the hypertrophic marker gene,
      atrial natriuretic peptide.
AB  - In neonatal rat ventricular myocytes, activation of receptors that couple to the
      G(q) family of heterotrimeric G proteins causes hypertrophic growth, together
      with expression of "hypertrophic marker" genes, such as atrial natriuretic
      peptide (ANP) and myosin light chain 2 (MLC2). As reported previously for other
      G(q)-coupled receptors, stimulation of alpha(1)-adrenergic receptors with
      phenylephrine (50 microM) caused phosphorylation of epidermal growth factor (EGF)
      receptors as well as activation of ERK1/2, cellular growth, and ANP
      transcription. These responses depended on EGF receptor activation. In marked
      contrast, stimulation of G(q)-coupled purinergic receptors with UTP caused EGF
      receptor phosphorylation, ERK1/2 activation, and cellular growth but minimal
      increases in ANP transcription. UTP inhibited phenylephrine-dependent
      transcription from ANP and MLC2 promoters but not transcription from myoglobin
      promoters or from AP-1 elements. Myocardin is a muscle-specific transcription
      enhancer that activates transcription from ANP and MLC2 promoters but not
      myoglobin promoters or AP-1 elements. UTP inhibited ANP and MLC2 responses to
      overexpressed myocardin but did not inhibit responses to c-Jun, GATA4, or serum
      response factor, all of which are active in nonmuscle cells. Thus, UTP inhibits
      transcriptional responses to phenylephrine only at cardiac-specific promoters,
      and this may involve the muscle-specific transcription enhancer, myocardin. These
      studies show that EGF receptor activation is necessary but not sufficient for ANP
      and MLC2 responses to activation of G(q)-coupled receptors in ventricular
      myocytes, because inhibitory mechanisms can oppose such stimulation. ANP is a
      compensatory and protective factor in cardiac hypertrophy, and mechanisms that
      reduce its generation need to be defined.

PMID- 14676213
TI  - Nck-1 antagonizes the endoplasmic reticulum stress-induced inhibition of
      translation.
AB  - Eukaryotic cells have developed specific mechanisms to overcome environmental
      stress. Here we show that the Src homology 2/3 (SH2/SH3) domain-containing
      protein Nck-1 prevents the unfolded protein response normally induced by
      pharmacological endoplasmic reticulum (ER) stress agents. Overexpression of Nck-1
      enhances protein translation, whereas it abrogates eukaryotic initiation factor
      2alpha (eIF2alpha) phosphorylation and inhibition of translation in response to
      tunicamycin or thapsigargin treatment. Nck-1 overexpression also attenuates
      induction of the ER chaperone, the immunoglobulin heavy chain-binding protein
      (BiP), and impairs cell survival in response to thapsigargin. We provided
      evidence that in these conditions, the effects of Nck on the unfolded protein
      response (UPR) involve its second SH3 domain and a calyculin A-sensitive
      phosphatase activity. In addition, we demonstrated that protein translation is
      reduced in mouse embryonic fibroblasts lacking both Nck isoforms and is enhanced
      in similar cells expressing high levels of Nck-1. In these various mouse
      embryonic fibroblasts, we also provided evidence that Nck modulates the
      activation of the ER resident eIF2alpha kinase PERK and consequently the
      phosphorylation of eIF2alpha on Ser-51 in response to stress. Our study
      establishes that Nck is required for optimal protein translation and demonstrates
      that, in addition to its adaptor function in mediating signaling from the plasma
      membrane, Nck also mediates signaling from the ER membrane compartment.

PMID- 14676214
TI  - Functional analysis of multiple single-stranded DNA-binding proteins from
      Methanosarcina acetivorans and their effects on DNA synthesis by DNA polymerase
      BI.
AB  - Single-stranded DNA-binding proteins and their functional homologs, replication
      protein A, are essential components of cellular DNA replication, repair and
      recombination. We describe here the isolation and characterization of multiple
      replication protein A homologs, RPA1, RPA2, and RPA3, from the archaeon
      Methanosarcina acetivorans. RPA1 comprises four single-stranded DNA-binding
      domains, while RPA2 and RPA3 are each composed of two such domains and a zinc
      finger domain. Gel filtration analysis suggested that RPA1 exists as
      homotetramers and homodimers in solution, while RPA2 and RPA3 form only
      homodimers. Unlike the multiple RPA proteins found in other Archaea and
      eukaryotes, each of the M. acetivorans RPAs can act as a distinct single-stranded
      DNA-binding protein. Fluorescence resonance energy transfer and fluorescence
      polarization anisotropy studies revealed that the M. acetivorans RPAs bind to as
      few as 10 single-stranded DNA bases. However, more stable binding is achieved
      with single-stranded DNA of 18-23 bases, and for such substrates the estimated Kd
      was 3.82 +/- 0.28 nM, 173.6 +/- 105.17 nM, and 5.92 +/- 0.23 nM, for RPA1, RPA2,
      and RPA3, respectively. The architectures of the M. acetivorans RPAs are
      different from those of hitherto reported homologs. Thus, these proteins may
      represent novel forms of replication protein A. Most importantly, our results
      show that the three RPAs and their combinations highly stimulate the primer
      extension capacity of M. acetivorans DNA polymerase BI. Although bacterial SSB
      and eukaryotic RPA have been shown to stimulate DNA synthesis by their cognate
      DNA polymerases, our findings provide the first in vitro biochemical evidence for
      the conservation of this property in an archaeon.

PMID- 14676215
TI  - Association of the chaperone alphaB-crystallin with titin in heart muscle.
AB  - alphaB-crystallin, a major component of the vertebrate lens, is a chaperone
      belonging to the family of small heat shock proteins. These proteins form
      oligomers that bind to partially unfolded substrates and prevent denaturation.
      alphaB-crystallin in cardiac muscle binds to myofibrils under conditions of
      ischemia, and previous work has shown that the protein binds to titin in the I
      band of cardiac fibers (Golenhofen, N., Arbeiter, A., Koob, R., and Drenckhahn,
      D. (2002) J. Mol. Cell. Cardiol. 34, 309-319). This part of titin extends as
      muscles are stretched and is made up of immunoglobulin-like modules and two
      extensible regions (N2B and PEVK) that have no well defined secondary structure.
      We have followed the position of alphaB-crystallin in stretched cardiac fibers
      relative to a known part of the titin sequence. alphaB-crystallin bound to a
      discrete region of the I-band that moved away from the Z-disc as sarcomeres were
      extended. In the physiological range of sarcomere lengths, alphaB-crystallin
      bound in the position of the N2B region of titin, but not to PEVK. In
      overstretched myofibrils, it was also in the Ig region between N2B and the Z
      disc. Binding between alphaB-crystallin and N2B was confirmed using recombinant
      titin fragments. The Ig domains in an eight-domain fragment were stabilized by
      alphaB-crystallin; atomic force microscopy showed that higher stretching forces
      were needed to unfold the domains in the presence of the chaperone. Reversible
      association with alphaB-crystallin would protect I-band titin from stress liable
      to cause domain unfolding until conditions are favorable for refolding to the
      native state.

PMID- 14676216
TI  - A novel interaction between kinesin and p120 modulates p120 localization and
      function.
AB  - p120-catenin exists in a membrane-associated cadherin-bound pool, a cytosolic
      pool that affects Rho GTPases, and a nuclear pool that is thought to associate
      with the methylation-relevant transcriptional repressor Kaiso. We show here that
      cytoplasmic p120 can also associate both directly and indirectly with the
      microtubule network, and that p120 traffics along microtubules toward their plus
      ends. The direct binding required most of the armadillo repeats and was mutually
      exclusive for interaction with E-cadherin. Perturbing the p120-microtubule
      interaction with nocodazole or taxol markedly affected both the tubulin
      interaction and the balance between cytoplasmic and nuclear p120. The indirect
      binding occurred via a novel interaction between a segment of the p120 N-terminal
      domain and conventional kinesin heavy chains. Selective uncoupling of the p120
      kinesin interaction by overexpression of the respective p120 and kinesin-binding
      fragments promoted nuclear p120 accumulation. In addition, expression of full
      length kinesin reduced the nuclear accumulation of p120 and blocked the branching
      phenotype associated with p120 overexpression. Taken together, the data suggest
      that kinesin affects both the targeting and activity of p120 at several cellular
      locations.

PMID- 14676217
TI  - High glucose enhances interleukin-6-induced vascular endothelial growth factor
      165 expression via activation of gp130-mediated p44/42 MAPK-CCAAT/enhancer
      binding protein signaling in gingival fibroblasts.
AB  - Diabetic patients are susceptible to severe inflammatory periodontitis
      manifesting as swollen gingiva with bleeding, but the underlying mechanism is not
      well understood. Our purpose was to determine the effect of a high glucose (HG)
      condition on the interleukin-6/soluble interleukin-6 receptor (IL-6/sIL-6R)
      induced activation of signaling and vascular endothelial growth factor (VEGF)
      expression in human gingival fibroblasts (HGFs). In this study, HGFs were
      cultured for at least two passages under a normal glucose (NG; 5.5 mM) condition
      or high glucose (25 mM) condition. Importantly, the HG condition significantly
      induced expression of gp130 mRNA in HGFs compared with levels in control cells.
      Consistent with the expression of its mRNA, the HG condition also increased the
      expression of gp130 protein, and phosphorylation of the tyrosine residue by gp130
      was enhanced significantly by IL-6/sIL-6R stimulation. Furthermore, the HG
      condition enhanced the IL-6/sIL-6R-induced phosphorylation of p44/42 MAPK and led
      to subsequent activation of CCAAT/enhancer binding protein in nuclei. In
      contrast, there was no significant difference in phosphorylation of JNK between
      the HG and NG condition. Interestingly, HGFs increased IL-6/sIL-6R-induced
      VEGF165 mRNA expression and VEGF165 secretion under the HG condition compared
      with levels under the NG condition. In contrast, the induction of VEGF165
      secretion was partially inhibited by PD98059 (selective p44/42 MAPK inhibitor)
      under the HG condition. In addition, the VEGF165 secretion was completely
      inhibited by the combination of PD98059 and SP600125 (JNK inhibitor). Our
      findings suggest that the HG condition indirectly increases VEGF expression via
      activation of gp130-mediated p44/42 MAPK-CCAAT/enhancer binding protein signaling
      in HGFs. Thus, elevated VEGF secretion in HGFs under the HG condition may play a
      role in the development of the severe periodontitis observed in diabetic
      patients.

PMID- 14676218
TI  - Human mitochondrial glutaredoxin reduces S-glutathionylated proteins with high
      affinity accepting electrons from either glutathione or thioredoxin reductase.
AB  - Glutaredoxins catalyze glutathione-dependent thiol disulfide oxidoreductions via
      a GSH-binding site and active cysteines. Recently a second human glutaredoxin
      (Grx2), which is targeted to either mitochondria or the nucleus, was cloned. Grx2
      contains the active site sequence CSYC, which is different from the conserved
      CPYC motif present in the cytosolic Grx1. Here we have compared the activity of
      Grx2 and Grx1 using glutathionylated substrates and active site mutants. The
      kinetic studies showed that Grx2 catalyzes the reduction of glutathionylated
      substrates with a lower rate but higher affinity compared with Grx1, resulting in
      almost identical catalytic efficiencies (k(cat)/K(m)). Permutation of the active
      site motifs of Grx1 and Grx2 revealed that the CSYC sequence of Grx2 is a
      prerequisite for its high affinity toward glutathionylated proteins, which comes
      at the price of lower k(cat). Furthermore Grx2 was a substrate for NADPH and
      thioredoxin reductase, which efficiently reduced both the active site disulfide
      and the GSH-glutaredoxin intermediate formed in the reduction of glutathionylated
      substrates. Using this novel electron donor pathway, Grx2 reduced low molecular
      weight disulfides such as CoA but with particular high efficiency
      glutathionylated substrates including GSSG. These results suggest an important
      role for Grx2 in protection and recovery from oxidative stress.

PMID- 14676219
TI  - Raloxifene prevents cardiac hypertrophy and dysfunction in pressure-overloaded
      mice.
AB  - 17beta-estradiol reduces myocardial hypertrophy and left ventricular mass,
      suggesting that the selective estrogen receptor modulator raloxifene may have
      similar effects. However, it is not clear whether raloxifene inhibits both
      cardiac hypertrophy and dysfunction. We used transverse aortic-banded mice to
      produce pressure-overload cardiac hypertrophy and used neonatal rat ventricular
      cardiomyocytes to investigate the cellular mechanisms of raloxifene on cardiac
      hypertrophy. Left ventricular mass and fractional shortening of mice hearts were
      measured by transthoracic echocardiography. Protein synthesis of cardiomyocytes
      was evaluated by incorporation of [3H]leucine into cardiomyocytes exposed to
      angiotensin II. Phosphorylation of mitogen-activated protein (MAP) kinase was
      also observed in cardiomyocytes. Raloxifene prevented increases in left
      ventricular mass and decreases of fractional shortening at 4 weeks after aortic
      banding. Pretreatment with raloxifene before angiotensin II stimulation inhibited
      the increase in [3H]leucine incorporation into neonatal rat cardiomyocytes in a
      concentration-dependent manner. This inhibition was partially but not
      significantly attenuated by N(G)-nitro-L-arginine methyl ester (L-NAME), an
      inhibitor of nitric oxide synthase, and completely abolished by ICI182780, an
      estrogen receptor antagonist. Although the phosphorylation of p38 MAP kinase, c
      Jun N-terminal kinase (JNK), or extracellular signal-regulated protein kinase
      (ERK) in cardiomyocytes was significantly increased by angiotensin II stimulation
      as compared with the control, pretreatment with raloxifene attenuated p38 MAP
      kinase phosphorylation, but neither JNK nor ERK phosphorylation. We conclude that
      raloxifene inhibits cardiac hypertrophy and dysfunction and that the inhibition
      of p38 MAP kinase phosphorylation after the stimulation of estrogen receptors may
      be involved in the cellular mechanisms of this agent.

PMID- 14676220
TI  - Effect of birth weight on blood pressure and body size in early adolescence.
AB  - The fetal programming theory that birth weight contributes to blood pressure or
      body size in later life is examined in this study. A prospective longitudinal
      study was conducted on subjects who were examined as newborns and prospectively
      interviewed and re-examined at 11 to 14 years old. Low birth weight (<2500 g) was
      present in 36% of the sample. The adolescent examination included measurements of
      blood pressure (BP), both auscultation and oscillometric methods; anthropometrics
      (height, weight, and body mass index [BMI]); health status; and health behaviors.
      Data were analyzed on 250 subjects. Correlation coefficients of birth weight with
      all BP measures were nonsignificant, except for the last auscultated diastolic BP
      (r=0.19, P<0.01), which had a positive relationship. The simple correlation
      coefficients of birth weight with adolescent body size were significant and
      positive for weight and BMI. After multiple linear regression analyses with
      adjustments for age, Tanner stage, and gestational age, there was no significant
      effect of birth weight on adolescent weight or BMI. No significant correlations
      were detected for ponderal index at birth with adolescent measures. This study,
      which includes a substantial portion of low-birth-weight cases (36%), indicates
      that birth weight does not correlate negatively with later BP. These results do
      not support the low-birth-weight theory and indicate that childhood factors that
      are more proximal have a greater effect on adolescent BP than intrauterine
      factors.

PMID- 14676221
TI  - Neurogenic hypertension: is the enigma of its origin near the solution?

PMID- 14676222
TI  - Seventh report of the Joint National Committee on Prevention, Detection,
      Evaluation, and Treatment of High Blood Pressure and evidence from new
      hypertension trials.

PMID- 14676224
TI  - Myocardial gene and cell delivery.
AB  - Although we now have the tools to introduce vectors and stem cells into specific
      myocardial locations, these devices are yet to be matched by comparable advances
      in molecular virology, cell biology, and our understanding of the pathophysiology
      of ischaemic heart disease

PMID- 14676223
TI  - Procedure guidelines for radionuclide myocardial perfusion imaging.

PMID- 14676225
TI  - Non-contact mapping of the left ventricle and new insights into the mechanisms
      for success of biventricular pacing.
AB  - Results from cardiac resynchronisation therapy are likely to improve as methods
      for identifying likely responders and the optimum site for lead placement become
      more refined

PMID- 14676227
TI  - From malignant mutations to malignant domains: the continuing search for
      prognostic significance in the mutant genes causing hypertrophic cardiomyopathy.
AB  - The genetic causes of hypertrophic cardiomyopathy are diverse and thus present
      challenges in the development of genetic tests to identify patients at risk

PMID- 14676226
TI  - Management of valvar aortic stenosis in children.
AB  - What is the best treatment for the child with valvar aortic stenosis-balloon or
      surgical valvotomy?

PMID- 14676229
TI  - Long QT syndrome and life threatening arrhythmia in a newborn: molecular
      diagnosis and treatment response.
AB  - Intrauterine and neonatal manifestations of congenital long QT syndrome are
      associated with a high cardiac risk, particularly when atrioventricular block and
      excessive QT prolongation (> 600 ms(1/2)) are present. In a female newborn with
      these features, treatment with propranolol and mexiletine led to complete
      reduction of arrhythmia that was maintained 1.5 years later. High throughput
      genetic analysis found a sodium channel gene (LQT3) mutation. Disappearance of
      the 2:1 atrioventricular block and QTc shortening (from 740 ms(1/2) to 480
      ms(1/2)), however, was achieved when mexiletine was added to propranolol. This
      effect was considered to be possibly genotype related. Early onset forms of long
      QT syndrome may benefit from advanced genotyping.

PMID- 14676228
TI  - Is impairment of ischaemic preconditioning by sulfonylurea drugs clinically
      important?
AB  - In the UGDP study, published in the 1970s, a high incidence of cardiovascular
      mortality was found in patients treated with the sulfonylurea agent tolbutamide.
      Impaired ischaemic preconditioning is presumed to be the most important mechanism
      for the excess cardiovascular mortality observed. However, as tolbutamide has
      only a low affinity for cardiac sulfonylurea receptors, interference with
      ischaemic preconditioning seems unlikely to account for this excess mortality.
      Several smaller studies also failed to establish a definite link between
      sulfonylurea treatment before acute myocardial infarction and in-hospital
      mortality. However, when the myocardium becomes exposed to repeated or prolonged
      periods of ischaemia, ischaemic preconditioning may become clinically important.
      Myocardial ischaemia can also develop during emergency or elective angioplasty
      and during coronary bypass surgery. Therefore discontinuation of sulfonylurea
      treatment should be considered in these circumstances.

PMID- 14676230
TI  - Calcium channel blocker induced gum hypertrophy: no class distinction.

PMID- 14676231
TI  - Variable left ventricular activation pattern in patients with heart failure and
      left bundle branch block.
AB  - OBJECTIVE: To determine the left ventricular (LV) activation pattern in patients
      with chronic heart failure and left bundle branch block (LBBB) on ECG. DESIGN:
      Prospective study. SETTING: Tertiary cardiology referral centre in Hong Kong.
      PATIENTS: Seven patients with LV ejection fraction < 35% and typical LBBB on ECG
      with QRS duration > or = 130 ms were recruited. Five of them had non-ischaemic
      dilated cardiomyopathy. METHODS: Non-contact mapping was used to investigate the
      LV global activation sequences. Tissue Doppler imaging was performed with the LV
      mapping and correlated with the activation sequences. RESULTS: Three patients had
      preserved left bundle activation despite LBBB on ECG. Conduction block was
      detected in four patients during LV activation and the other three had
      homogeneous depolarisation propagation within the left ventricle. The latest
      segment of activation was located in either the lateral or the posterior region.
      Tissue Doppler imaging correlated well with non-contact mapping to locate the
      conduction block and the latest segment of activation. CONCLUSIONS: LV
      endocardial activation sequences in patients with chronic heart failure and LBBB
      are variable. This may have implications for patient selection for treatment with
      cardiac resynchronisation.

PMID- 14676232
TI  - Neoplastic shock.

PMID- 14676233
TI  - Growth of girls who later develop coronary heart disease.
AB  - OBJECTIVE: To determine the path of growth of girls who later develop coronary
      heart disease. DESIGN: Follow up study of girls whose body size at birth, during
      infancy, and childhood up to age 12 years was recorded. SETTING: Helsinki,
      Finland. PARTICIPANTS: 4130 girls who were born between 1934 and 1944, attended
      child welfare clinics in Helsinki, and were still resident in Finland in 1971.
      MAIN OUTCOME MEASURE: Hospital admission or death from coronary heart disease.
      RESULTS: In comparison with boys in the same cohort who later developed coronary
      heart disease the 87 girls were short at birth, rather than thin, had
      compensatory growth in height during infancy, became thin, and thereafter had a
      rapid increase in weight and body mass index. In a combined analysis the hazard
      ratios for coronary heart disease were 1.17 (95% confidence interval (CI) 1.03 to
      1.32, p = 0.02) for each 1 cm decrease in length at birth, 1.52 (95% CI 1.23 to
      1.89, p < 0.001) for each standard deviation score increase in body mass index
      after age 3 years, and 1.63 (95% CI 1.09 to 2.42, p = 0.02) for each decrease in
      level of education. CONCLUSIONS: Though broadly similar, the paths of growth
      associated with the later development of coronary heart disease differ in girls
      and boys. This may be because girls are less vulnerable to undernutrition in
      utero and are better able to sustain postnatal growth in an adverse environment.

PMID- 14676234
TI  - Extreme hypertrophic cardiomyopathy.

PMID- 14676236
TI  - Impairment of cardiopulmonary receptor sensitivity in the early phase of heart
      failure.
AB  - OBJECTIVES: To characterise the efficiency of the cardiopulmonary baroreflex
      system in the early phase of heart failure and its relation to limitation of
      physical activity. DESIGN: Forearm blood flow (venous occlusion plethysmography),
      vascular resistance, and central venous pressure (CVP), estimated from an
      antecubital vein, were measured in the supine position at baseline and 15 minutes
      after application of lower body negative pressure at -7 and -14 mm Hg (receptor
      downloading) or leg raising (receptor loading). SUBJECTS: Heart failure patients
      without limitation (NYHA class I; n = 18) or with slight limitation of physical
      activity (NYHA class II; n = 13), and 11 healthy controls. RESULTS: The
      efficiency of the cardiopulmonary baroreflex function, expressed by the slope of
      the relation between CVP changes and the corresponding changes of calculated
      forearm vascular resistance (gain), was reduced both in NYHA class I patients
      (mean (SD) -1.99 (0.83) v -2.78 (0.66) in controls; p < 0.05) and NYHA class II
      patients (-1.29 (0.5); p<0.001 v controls). However, change in peripheral
      vascular resistance during preload increase was similar in controls (-3.3 (0.9)
      units) and in NYHA class I patients (-3.3 (2.1) units; NS v controls), and was
      significantly reduced only in NYHA class II patients (-1.6 (1.3) units, p < 0.03
      v controls). The gain in the cardiopulmonary reflex was related to the distance
      walked during the six minute corridor test. CONCLUSIONS: A reduced tonic efficacy
      of the cardiopulmonary reflex system is already detectable in the early phase of
      heart failure, the impairment in acute response to preload increase being
      detectable only in symptomatic patients.

PMID- 14676235
TI  - Raised concentrations of macrophage colony stimulating factor in severe unstable
      angina beyond the acute phase are strongly predictive of long term outcome.
AB  - OBJECTIVE: To evaluate the long term prognostic value of macrophage colony
      stimulating factor (MCSF), interleukin-6 (IL-6), and tumour necrosis factor alpha
      (TNFalpha) measured in serum six weeks after the occurrence of unstable angina.
      SUBJECTS: 119 consecutive patients, mean (SD) age 58 (10) years, with severe
      unstable angina (Braunwald class IIIb); controls were 96 subjects of similar age
      and sex distribution. DESIGN: MCSF, IL-6, and TNFalpha were measured on
      admission, at discharge, and six weeks later, and the patients were followed for
      two years. Clinical end points were: cardiac death, readmission for acute
      coronary syndromes, and revascularisation. SETTING: District general hospital.
      RESULTS: 113 patients completed follow up, during which two died of non-cardiac
      causes. Of the remaining 111 patients, 39 (35.1%) had a cardiac event (two
      deaths, 15 revascularisations, and 22 readmissions for acute coronary syndromes).
      MCSF and IL-6 concentrations at six weeks were higher in patients with cardiac
      events than in those without (424 v 306 pg/ml, p = 0.0008, and 6.6 v 4.5 pg/ml, p
      = 0.01, respectively). Cytokine concentrations at six weeks were also
      significantly higher than in the control group. Logistic regression analysis
      showed that MCSF concentrations were the only independent predictors of future
      events, with an adjusted odds ratio for events of 4.1 (95% confidence interval
      1.1 to 14.8; p = 0.03). The two year survival free of cardiac events was
      significantly lower in patients with MCSF concentrations in the highest tertile
      (values > or = 468 pg/ml) than in those with values < 468 pg/ml. CONCLUSIONS:
      Increased MCSF concentrations beyond the acute phase are strongly predictive of
      long term outcome in patients with severe unstable angina.

PMID- 14676237
TI  - Electron beam tomography of an interpulmonary saddle embolus.

PMID- 14676238
TI  - Relation between aortic stiffness and left ventricular diastolic function in
      patients with hypertension, diabetes, or both.
AB  - OBJECTIVE: To evaluate aortic function and its relation to left ventricular
      diastolic function in patients with hypertension, diabetes, or both, without
      coronary artery disease. METHODS: Study groups were composed of 27 healthy
      participants and 25 patients with hypertension, 24 with diabetes, and 18 with
      hypertension and diabetes. Coronary artery disease was excluded in all of the
      study participants. Aortic strain and distensibility were calculated from the
      aortic diameters measured by echocardiography and blood pressure obtained by
      sphygmomanometry. RESULTS: There were significant differences between the control
      and the patient groups (hypertensive, diabetic, and diabetic-hypertensive) in
      aortic strain (mean (SD) 18 (8)% v 11 (7)%, 9 (3)%, and 8 (3)%, respectively, p <
      0.001) and distensibility (10 (5.1) v 3.1 (1.5), 5.1 (2.8), and 2 (0.9)
      cm2/dyn/10(3), respectively, p < 0.001). In a multivariate analysis, the
      parameter most closely related to the deceleration time in the control group was
      aortic distensibility (standardised beta coefficient -0.50, p = 0.002, overall R2
      = 0.25). In the patient group, the parameter most closely related to deceleration
      time was also aortic distensibility (standardised beta coefficient -0.36, p =
      0.009, overall R2 = 0.13). Even though the study group variable was entered in to
      the multivariate model, aortic distensibility was found to be the parameter most
      closely related to deceleration time (standardised beta coefficient -0.48, p <
      0.001, overall R2 = 0.22). CONCLUSION: Aortic stiffness is increased in patients
      with hypertension, diabetes, or both even after the exclusion of coronary artery
      disease. Aortic stiffness and left ventricular diastolic dysfunction are also
      associated in these patients.

PMID- 14676239
TI  - Rhabdomyoma as accessory pathway: electrophysiologic and morphologic
      confirmation.

PMID- 14676240
TI  - Non-contact left ventricular endocardial mapping in cardiac resynchronisation
      therapy.
AB  - BACKGROUND: Up to 30% of patients with heart failure do not respond to cardiac
      resynchronisation therapy (CRT). This may reflect placement of the coronary sinus
      lead in regions of slow conduction despite optimal positioning on current
      criteria. OBJECTIVES: To characterise the effect of CRT on left ventricular
      activation using non-contact mapping and to examine the electrophysiological
      factors influencing optimal left ventricular lead placement. METHODS: and
      results: 10 patients implanted with biventricular pacemakers were studied. In
      six, the coronary sinus lead was found to be positioned in a region of slow
      conduction with an average conduction velocity of 0.4 m/s, v 1.8 m/s in normal
      regions (p < 0.02). Biventricular pacing with the left ventricle paced 32 ms
      before the right induced the optimal mean velocity time integral and timing for
      fusion of depolarisation wavefronts from the right and left ventricular pacing
      sites. Pacing outside regions of slow conduction decreased left ventricular
      activation time and increased cardiac output and dP/dt(max) significantly.
      CONCLUSIONS: In patients undergoing CRT for heart failure, non-contact mapping
      can identify regions of slow conduction. Significant haemodynamic improvements
      can occur when the site of left ventricular pacing is outside these slow
      conduction areas. Failure of CRT to produce clinical benefits may reflect left
      ventricular lead placement in regions of slow conduction which can be overcome by
      pacing in more normally activating regions.

PMID- 14676241
TI  - Unusual method for occlusive coronary sinus angiography.

PMID- 14676242
TI  - Does the use of a syncope diagnostic protocol improve the investigation and
      management of syncope?
AB  - OBJECTIVES: To assess the efficacy of a protocol designed to improve the
      diagnosis and management of syncope. DESIGN: Prospective outcome analysis of all
      patients presenting with syncope for the 12 month period from 1 November 2000 to
      31 October 2001, compared with a retrospective study of all patients presenting
      with syncope during the calendar year 1998. Use of the protocol commenced in
      September 2000. SETTING: Eastbourne District General Hospital, serving a
      population of approximately 250 000; 25% are older than 65 years. SUBJECTS: 421
      consecutive patients presenting with syncope, investigated prospectively in
      January 2000 and compared with 660 patients retrospectively analysed for the
      calendar year 1998. RESULTS: In 1998, 71% of patients with syncope received a
      diagnostic classification. In January 2000 there was an appropriate diagnostic
      hypothesis for every patient. Ultimately a diagnosis was made for 78% of patients
      according to accepted criteria (p = 0.003). Use of tests with the highest
      diagnostic effectiveness, such as tilt tests, increased in 2001 and many tests
      were used more appropriately (such as echocardiography). However, non-diagnostic
      tests were still frequently used (such as chest radiography,
      electroencephalography, and carotid Doppler studies). Costs of investigation and
      hospital stay rose from pound 611 to pound 1384 (euro;874 to euro;1980) per
      patient (p < 0.001), with cost per diagnosis increasing from pound 870
      (euro;1245) in 1998 to pound 1949 (euro;2790) (p < 0.001). CONCLUSION: The
      syncope protocol improved diagnosis and the use of appropriate investigations.
      However, significant inappropriate investigation and hospital admission still
      occurred. The protocol allowed reliable triage of syncopal patients into high and
      low risk groups.

PMID- 14676243
TI  - Pacemaker syndrome.

PMID- 14676245
TI  - Echocardiographic diagnosis of cor triatriatum sinister in the adult.

PMID- 14676244
TI  - Long term follow up of radiofrequency catheter ablation of atrial flutter:
      clinical course and predictors of atrial fibrillation occurrence.
AB  - OBJECTIVES: To evaluate the time to onset and the predictors of atrial
      fibrillation (AF) during long term follow up of patients with typical atrial
      flutter (AFL) treated with transisthmic ablation. DESIGN: Prospective multicentre
      study. METHODS AND RESULTS: 383 patients (75.4% men, mean (SD) age 61.7 (11.1)
      years) who underwent transisthmic ablation for typical AFL were investigated. In
      239 patients (62.4%) AF was present before ablation. Ablation proved successful
      in 367 patients (95.8%). During a mean (SD) follow up of 20.5 (12.4) months,
      41.5% of patients reported AF. The cumulative probability of postablation AF
      increased continuously as time passed: it was 22% at six months, 36% at one year,
      50% at two years, 58% at three years, and 63% at four years. CONCLUSIONS: AF
      occurred in a large proportion of patients after transisthmic catheter ablation
      of typical AFL. The occurrence of AF was progressive during follow up.
      Preablation AF, age < 65 years, and left atrial size > 50 mm are associated with
      postablation AF occurrence.

PMID- 14676246
TI  - Mechanism of improvement in exercise capacity after the maze procedure combined
      with mitral valve surgery.
AB  - OBJECTIVE: To clarify the mechanism of improvement in exercise capacity after the
      maze procedure. DESIGN: Retrospective study. SETTING: Tertiary referral centre.
      PATIENTS: 26 patients (mean (SD) age 57 (9) years) with atrial fibrillation (AF)
      and mitral valve disease were studied with echocardiography and cardiopulmonary
      exercise testing before and after the maze procedure combined with mitral valve
      surgery. Of these, eight had persistent AF and 18 had restored sinus rhythm (SR)
      by the surgery. Six patients (mean (SD) age 59 (12) years) with AF undergoing
      mitral valve surgery without the maze procedure who had cardiopulmonary exercise
      testing before and after the surgery formed the control group. MAIN OUTCOME
      MEASURES: Echocardiographic parameters of atrial function were measured from
      transmitral flow recordings. Peak oxygen uptake (VO2) and the slope of the
      relation between VO2 and workload (ratio of DeltaVO2 to Delta work) were
      determined as indices of exercise capacity. RESULTS: The degree of improvements
      in peak VO2 and the ratio of DeltaVO2 to Delta work after the mitral valve
      surgery was comparable between the maze and control group. It was also comparable
      between patients with and those without successfully restored SR after the maze
      procedure. The degree of the increase in peak VO2 correlated with the change in
      left atrial diameter (r = -0.40, p = 0.047) but atrial contraction did not
      correlate with the increase. CONCLUSIONS: Improvement in exercise capacity may
      not be caused by restored SR and atrial contraction but may at least partly
      relate to the reduction of left atrial size and improvement of haemodynamic
      variables by the surgery.

PMID- 14676248
TI  - Long term results of percutaneous balloon valvoplasty of congenital aortic
      stenosis: independent predictors of outcome.
AB  - OBJECTIVE: To evaluate long term results and independent predictors of outcome of
      aortic valvoplasty. DESIGN: Retrospective follow up study. Independent predictors
      of outcome identified by multiple logistic regression. SETTING: Tertiary referral
      centre. PATIENTS: 269 consecutive patients treated at the median age of 8 months
      (0-23 years): 80 (30%) under 4 weeks, 59 (22%) between 4 weeks and 1 year, and
      130 (48%) over 1 year. The follow up period was up to 14.8 years (median 5.3, in
      survivors 6.4 years). INTERVENTIONS: Percutaneous balloon valvoplasty with mean
      (SD) balloon to annulus ratio 0.97 (0.08). MAIN OUTCOME MEASURES: Restenosis > or
      = 70 mm Hg, grade 3 aortic insufficiency, cusps disruption, surgery, death, and
      valvoplasty failure (significant restenosis or insufficiency or surgery or
      death). RESULTS: The mortality rate was 10.4% (n = 28), the restenosis rate was
      16.7% (n = 45), significant insufficiency developed in 22.3% (n = 60), surgery
      was needed in 20.1% (n = 54), and "valvoplasty failure" occurred in 41.6% (n =
      112) patients. Mean (SEM) survival probability 14.4 years after the procedure was
      0.89 (0.02) and mean (SEM) probability of surgery-free survival was 0.50 (0.08).
      The independent predictors were as follows. For restenosis: small aortic annulus;
      for cusp disruption: large aortic annulus; for insufficiency: bicuspid aortic
      valve; for need for surgery: bicuspid aortic valve; for death: small aortic
      annulus, low left ventricular shortening fraction, and low sequential number of
      the valvoplasty; and for valvoplasty failure: small aortic annulus, bicuspid
      aortic valve, and high grade of mitral insufficiency. CONCLUSION: Independent
      predictors of unfavourable outcome are small aortic annulus, bicuspid aortic
      valve, poor function of left ventricle or mitral valve, and limited operator
      experience.

PMID- 14676249
TI  - Acute thrombosis of an extracardiac Fontan conduit.

PMID- 14676250
TI  - Balloon aortic valvoplasty in paediatric patients: progressive aortic
      regurgitation is common.
AB  - OBJECTIVE: To evaluate immediate and midterm results after balloon valvoplasty in
      a paediatric population with congenital aortic stenosis, giving special
      consideration to aortic regurgitation. DESIGN: Retrospective study. SETTING: Two
      tertiary referral centres for paediatric cardiology. PATIENTS: 70 consecutive
      patients, with an age range of 0-16.4 years. Group A infants < 3 months old (n =
      21). Group B children > 3 months old (n = 49). Median follow up time was 19.8
      months, range 0-158 months. INTERVENTION: All patients underwent balloon aortic
      valvoplasty. The balloon to annulus ratio was selected at a mean of 0.90 (range
      0.67-1.0). MAIN OUTCOME MEASURES: Doppler gradients and degree of aortic
      regurgitation. RESULTS: The pressure gradient dropped significantly with the
      intervention and increased mildly at follow up. Freedom from relevant aortic
      regurgitation (that is, moderate and severe) was initially lower in group A (75%
      v 90% after one month) but after two years the difference between the two groups
      was not significant (50% v 61%). Freedom from reintervention was significantly
      lower in group A (with 35% v 80%) after three years. CONCLUSION: Aortic balloon
      valvoplasty is safe and effective but has a high rate of early reintervention in
      infants with critical aortic stenosis. The major long term problem is progressive
      aortic regurgitation, which does not seem to be prevented by the use of small
      balloons.

PMID- 14676251
TI  - Pseudo-ventricular tachycardia: electrocardiographic artefact mimicking non
      sustained polymorphic ventricular tachycardia in a patient evaluated for syncope.

PMID- 14676252
TI  - G20210A prothrombin gene polymorphism and coronary ischaemic syndromes: a
      phenotype-specific meta-analysis of 12 034 subjects.
AB  - OBJECTIVE: To investigate the possible link between the G20210A prothrombin gene
      variant and different forms of ischaemic heart disease. DESIGN: Phenotype
      specific meta-analysis of 19 studies published within March 2002, globally
      including 4944 patients and 7090 controls. Sample size, inclusion criteria,
      geographical location, clinical presentation, age, cardiovascular risk factors,
      and angiographic extent of disease were extracted from each study. Analyses were
      done according to Mantel-Haenszel. RESULTS: Overall, the odds ratio (OR) for
      unspecified ischaemic heart disease associated with the 20210A allele was 1.21
      (95% confidence interval (CI) 0.99 to 1.59, n = 12 034). Similar findings were
      seen for acute coronary syndromes (unstable angina and myocardial infarction) and
      for myocardial infarction without age limits (OR 1.24, 95% CI 0.98 to 1.63, n =
      10 240; and OR 1.19, 95% CI 0.93 to 1.58, n = 9765). The effects were similar in
      male and female subjects. In the 1931 subjects < 55 years of age, the OR for
      myocardial infarction increased to 1.77 (95% CI 1.16 to 3.42) and in the 1359
      subjects < 45 years to 2.30 (95% CI 1.27 to 4.59). No significant association was
      found between the 20210A allele and the presence of angiographically documented
      coronary disease (OR 1.08, 95% CI 0.70 to 1.64, n = 3444). However, patients with
      0/1 vessel disease at angiography showed a greater prevalence of the A allele
      than those with multivessel disease (relative risk 2.0, 95% CI 1.2 to 3.1, n =
      2376). CONCLUSIONS: G20210A prothrombin gene polymorphism may represent a modest
      but significant risk factor for myocardial infarction at young ages and favour
      the expression of ischaemic heart disease among individuals who have a limited
      extent of coronary atherosclerosis at angiography.

PMID- 14676253
TI  - Interventional magnetic resonance imaging for guiding gene and cell transfer in
      the heart.
AB  - BACKGROUND: Interventional magnetic resonance imaging (iMRI) has the potential
      for guiding interventional cardiac procedures in real time. OBJECTIVES: To test
      the feasibility of iMRI guided gene and cell transfer to the heart and to monitor
      myocardial remodelling after myocardial infarction in a rat model. METHODS: The
      MRI contrast agent GdDTPA, together with either Evans blue dye, or a recombinant
      adenovirus encoding the LacZ gene, or primary fibroblasts tagged by BrdU, were
      injected into the myocardium of rats under iMRI guidance. Rats were killed seven
      days after the injection and the hearts sectioned to identify the blue dye, LacZ
      expression, or fibroblast presence, respectively. In a parallel study, left
      ventricular area was measured before and after myocardial infarction and in sham
      operated rats by T1 weighted MRI and by echocardiography. RESULTS: Location of
      GdDTPA enhancement observed with iMRI at the time of injection was correlated
      with Evans blue stain, beta-gal expression, and the primary fibroblast location
      in histological studies. iMRI and echocardiography measured a comparable increase
      in left ventricular area at seven and 30 days after myocardial infarction. A good
      correlation was found between the iMRI and echocardiographic assessment of left
      ventricular area (r = 0.70; p < 0.0001) and change in left ventricular area with
      time (r = 0.75; p < 0.0001). CONCLUSIONS: The results show the feasibility and
      efficiency of iMRI guided intramyocardial injections, and the ability to monitor
      heart remodelling using iMRI. Genes, proteins, or cells for tissue engineering
      could be injected accurately into the myocardial scar under iMRI guidance.

PMID- 14676255
TI  - Pulmonary atresia with intact ventricular septum and right coronary artery to
      right ventricle fistula detected in utero.

PMID- 14676254
TI  - Detection of subclinical atherosclerosis by electron beam tomography in females
      with heterozygous familial hypercholesterolaemia.

PMID- 14676256
TI  - Adequate intracoronary adenosine doses to achieve maximum hyperaemia in coronary
      functional studies by pressure derived fractional flow reserve: a dose response
      study.

PMID- 14676258
TI  - Atrial and brain natriuretic peptides as markers of response to resynchronisation
      therapy.

PMID- 14676259
TI  - Clinical implications of the new definition of myocardial infarction.

PMID- 14676260
TI  - The French paradox: lessons for other countries.

PMID- 14676262
TI  - Participatory learning: a Swedish perspective.

PMID- 14676264
TI  - Transient abnormal Q waves during exercise electrocardiography.
AB  - Myocardial ischaemia during exercise electrocardiography is usually manifested by
      ST segment depression or elevation. Transient abnormal Q waves are rare, as Q
      waves indicate an old myocardial infarction. The case of a patient with exercise
      induced transient abnormal Q waves is reported. The potential mechanisms involved
      in the development of such an abnormality and its clinical implications are
      discussed.

PMID- 14676265
TI  - Paradoxical increase of pulmonary vascular resistance during testing of inhaled
      iloprost.
AB  - The case of a 14 month old girl with primary pulmonary hypertension treated with
      domiciliary oxygen is described. After invasive evaluation and testing of nitric
      oxide with very good response, the testing was repeated to study the effect of
      inhaled iloprost on pulmonary vascular resistance (PVR). An unexpected and severe
      increase of PVR was observed, rising from 392 dynes x s x cm(-5) with oxygen to a
      maximum of 1192 dynes x s x cm(-5) with oxygen and iloprost. Underlying
      ventilatory and technical problems were excluded. While inhaled iloprost has been
      described to be highly effective in the treatment of primary pulmonary
      hypertension, the possibility of contrary "paradoxical" reactions in isolated
      patients is emphasised, with a dramatic increase of PVR and a possible adverse
      outcome.

PMID- 14676266
TI  - Rhabdomyolysis induced by a single dose of a statin.
AB  - Statins have been shown to cause myotoxicity and rhabdomyolysis. In most cases
      rhabdomyolysis occurs following the use of these drugs for at least one week. A
      case of rhabdomyolysis after just a single dose of simvastatin is reported.

PMID- 14676267
TI  - Primary pericardial mesothelioma presenting as pericardial constriction: a case
      report.
AB  - A 19 year old man presented with a six month history of chest pain, dyspnoea, and
      lethargy and was found on an echocardiogram to have a dilated left ventricle with
      a small pericardial effusion. Ramipril and a course of steroids were tried but
      serial echocardiograms showed a persistently thickened pericardium and slowly
      developing features of constriction. On computed tomography, a large mediastinal
      mass encasing the heart, along with para-aortic and paratracheal lymphadenopathy,
      was found. Right heart catheter studies showed equal pressures in all four
      chambers. His deteriorating clinical condition led to a pericardiectomy.
      Histology confirmed primary pericardial mesothelioma. The patient died soon after
      surgery.

PMID- 14676268
TI  - PKC at a glance.

PMID- 14676269
TI  - Intermediate filaments are dynamic and motile elements of cellular architecture.
AB  - Recent evidence showing that intermediate filaments (IFs) are dynamic, motile
      elements of the cytoskeletal repertoire of vertebrate cells has overturned the
      long-standing view that they simply form static 'space filling' cytoplasmic
      networks. In fact, many types of IF are now known to engage in a remarkable array
      of movements that are closely associated with their assembly, disassembly and
      subcellular organization. Some of these motile properties are intrinsic to IFs
      and others are attributable to molecular crosstalk with either microtubules or
      actin-containing microfilaments. This crosstalk is, to a large extent, mediated
      by molecular motors, including conventional kinesin and cytoplasmic dynein. These
      motors are responsible for the high-speed delivery of nonfilamentous IF
      precursors and short filaments to specific regions of the cytoplasm, where they
      assemble into long IFs. Interestingly, the patterns and speeds of IF movements
      vary in different cell types and even within different regions of the same cell.
      These differences in motility may be related to their interactions with different
      types of molecular motor and/or other factors, such as IF-associated proteins.

PMID- 14676270
TI  - GTPases and reactive oxygen species: switches for killing and signaling.
AB  - In neutrophils and other phagocytic cells, the small GTPase Rac is an essential
      regulator of a multi-component NADPH oxidase that produces high levels of
      superoxide, which kills invading pathogens. In many other cell types, Rac and
      newly discovered relatives of the neutrophil burst oxidase and its subunits have
      been found associated with production of reactive oxygen species, implicating
      superoxide production in a wide range of cellular processes not related to host
      defense. Although the precise role played by Rac in the regulation of these novel
      oxidases is not known, Rac does control the cellular redox state. Through these
      pro-oxidant mechanisms, Rac and the novel oxidases modify gene expression, cell
      proliferation, adhesion and many cell-specific functions.

PMID- 14676271
TI  - PIKE GTPase: a novel mediator of phosphoinositide signaling.
AB  - Phosphoinositide (PI) 3-kinase enhancer (PIKE) is a brain-specific GTPase that
      binds to PI 3-kinase and stimulates its lipid kinase activity. It exists in two
      forms: the first to be identified, PIKE-S, is shorter and exclusively nuclear; by
      contrast, the longer form, PIKE-L, resides in multiple intracellular
      compartments. Nerve growth factor treatment leads to PIKE-S activation by
      triggering the nuclear translocation of phospholipase C (PLC)-gamma 1, which acts
      as a physiological guanine nucleotide exchange factor (GEF) for PIKE-S through
      its Src-homology 3 (SH3) domain. Cytoplasmic PI 3-kinase and its lipid product
      phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] regulate the
      membrane translocation and activation of many signaling molecules by binding to
      their pleckstrin homology (PH) domains. However, little is known about the
      physiological roles of their nuclear counterparts. The nuclear PLC-gamma 1/PIKE
      S/PI 3-kinase signaling pathway seems to be an extension of the crosstalk between
      cytoplasmic PLC-gamma 1 and PI 3-kinase. PIKE-L contains a C-terminal extension
      consisting of an ADP ribosylation-GTPase-activating protein (ArfGAP) domain and
      two ankyrin repeats in addition to the N-terminal GTPase domain. PIKE-L could
      have additional, extranuclear functions, including regulation of postsynaptic
      signaling by metabotropic glutamate receptors.

PMID- 14676272
TI  - Kinesin dependent, rapid, bi-directional transport of ER sub-compartment in
      dendrites of hippocampal neurons.
AB  - Although spatially restricted Ca2+ release from the endoplasmic reticulum (ER)
      through intracellular Ca2+ channels plays important roles in various neuronal
      activities, the accurate distribution and dynamics of ER in the dendrite of
      living neurons still remain unknown. To elucidate these, we expressed fluorescent
      protein-tagged ER proteins in cultured mouse hippocampal neurons, and monitored
      their movements using time-lapse microscopy. We report here that a sub
      compartment of ER forms in relatively large vesicles that are capable, similarly
      to the reticular ER, of taking up and releasing Ca2+. The vesicular sub
      compartment of ER moved rapidly along the dendrites in both anterograde and
      retrograde directions at a velocity of 0.2-0.3 microm/second. Depletion of
      microtubules, overexpression of dominant-negative kinesin and kinesin depletion
      by antisense DNA reduced the number and velocity of the moving vesicles,
      suggesting that kinesin may drive the transport of the vesicular sub-compartment
      of ER along microtubules in the dendrite. Rapid transport of the Ca2+-releasable
      sub-compartment of ER might contribute to rapid supply of fresh ER proteins to
      the distal part of the dendrite, or to the spatial regulation of intracellular
      Ca2+ signaling.

PMID- 14676273
TI  - Localisation of histone macroH2A1.2 to the XY-body is not a response to the
      presence of asynapsed chromosome axes.
AB  - Histone macroH2A1.2 and the murine heterochromatin protein 1, HP1 beta, have both
      been implicated in meiotic sex chromosome inactivation (MSCI) and the formation
      of the XY-body in male meiosis. In order to get a closer insight into the
      function of histone macroH2A1.2 we have investigated the localisation of
      macroH2A1.2 in surface spread spermatocytes from normal male mice and in oocytes
      of XX and XYTdym1 mice. Oocytes of XYTdym1 mice have no XY-body or MSCI despite
      having an XY chromosome constitution, so the presence or absence of 'XY-body'
      proteins in association with the X and/or Y chromosome of these oocytes enables
      some discrimination between potential functions of XY-body located proteins. We
      demonstrate here that macroH2A1.2 localises to the X and Y chromatin of
      spermatocytes as they condense to form the XY-body but is not associated with the
      X and Y chromatin of XYTdym1 early pachytene oocytes. MacroH2A1.2 and HP1 beta co
      localise to autosomal pericentromeric heterochromatin in spermatocytes. However,
      the two proteins show temporally and spatially distinct patterns of association
      to X and Y chromatin.

PMID- 14676274
TI  - Analysis of the mechanism by which calcium negatively regulates the tyrosine
      phosphorylation cascade associated with sperm capacitation.
AB  - The capacitation of mammalian spermatozoa involves the activation of a cAMP
      mediated signal transduction pathway that drives tyrosine phosphorylation via
      mechanisms that are unique to this cell type. Controversy surrounds the impact of
      extracellular calcium on this process, with positive and negative effects being
      recorded in independent publications. We clearly demonstrate that the presence of
      calcium in the external medium decreases tyrosine phosphorylation in both human
      and mouse spermatozoa. Under these conditions, a rise in intracellular pH was
      recorded, however, this event was not responsible for the observed changes in
      phosphotyrosine expression. Rather, the impact of calcium on tyrosine
      phosphorylation in these cells was associated with an unexpected change in the
      intracellular availability of ATP. Thus, the ATP content of both human and mouse
      spermatozoa fell significantly when these cells were incubated in the presence of
      external calcium. Furthermore, the removal of glucose, or addition of 2
      deoxyglucose, decreased ATP levels within human spermatozoon populations and
      induced a corresponding decline in phosphotyrosine expression. In contrast, the
      mitochondrial inhibitor rotenone had no effect on either ATP levels or tyrosine
      phosphorylation. Addition of the affinity-labeling probe 8-N3 ATP confirmed our
      prediction that spermatozoa have many calcium-dependent ATPases. Moreover,
      addition of the ATPase inhibitor thapsigargin, increased intracellular calcium
      levels, decreased ATP and suppressed tyrosine phosphorylation. Based on these
      findings, the present study indicates that extracellular calcium suppresses
      tyrosine phosphorylation by decreasing the availability of intracellular ATP, and
      not by activating tyrosine phosphatases or inhibiting tyrosine kinases as has
      been previously suggested.

PMID- 14676275
TI  - Actin cytoskeleton remodelling via local inhibition of contractility at discrete
      microdomains.
AB  - Activation of conventional protein kinase C by phorbol ester triggers the Src
      dependent remodelling of the actin cytoskeleton and the formation of podosomes in
      vascular smooth muscle cells. Rearrangement of actin cytoskeleton in response to
      phorbol-12,13-dibutyrate is characterised by the simultaneous disassembly of
      peripheral actin stress fibres and focal adhesions, focal de novo actin
      polymerisation and actomyosin contraction in the cell center, indicating a
      spatially and temporally segregated, differential modulation of actin
      cytoskeleton stability and turnover. Taking advantage of the prominent actin
      cytoskeleton in A7r5 cells we show here, that the molecular basis for the local
      inhibition of contractility is the specific recruitment of p190RhoGAP to
      specialised microdomains at the focal adhesion/stress fibre interface, which are
      constitutively enriched in cortactin. The microdomains contain structurally
      altered actin filaments inaccessible to phalloidin. However, the filaments remain
      decorated with high molecular weight tropomyosins. Clustering of cortactin during
      podosome formation causes the rapid, local dispersion of myosin and tropomyosin,
      and interferes with the F-actin binding of h1calponin, consistent with a RhoGAP
      mediated reduction of contractility. Phorbol ester-induced podosome formation is
      efficiently blocked by expression of constitutively active Dia1, which leads to
      the dispersion of cortactin. The results provide direct evidence for the
      spatially restricted inhibition of contractility via the recruitment and
      accumulation of cortactin and p190RhoGAP.

PMID- 14676276
TI  - A domain-specific usherin/collagen IV interaction may be required for stable
      integration into the basement membrane superstructure.
AB  - Usherin is a basement membrane protein encoded by the gene associated with Usher
      syndrome type IIa, the most common deaf/blind disorder. This report demonstrates
      a specific interaction between type IV collagen and usherin in the basement
      membrane, with a 1:1 stoichiometry for binding. Genetic and biochemical
      approaches were used to explore the role of type IV collagen binding in usherin
      function. We demonstrate binding occurs between the LE domain of usherin and the
      7S domain of type IV collagen. A purified fusion peptide comprising the first
      four LE modules was shown to compete with full-length recombinant usherin for
      type IV collagen binding. However, synonymous fusion peptides with single amino
      acid substitutions resulting from missense mutations that were known to cause
      Usher syndrome type IIa in humans, failed to compete. Only mutations in loop b of
      the LE domain abolished binding activity. Co-immunoprecipitation and western blot
      analysis of testicular basement membranes from the Alport mouse model show a 70%
      reduction in type IV collagen is associated with a similar reduction in usherin,
      suggesting the usherin/collagen (IV) interaction stabilizes usherin in the
      basement membrane. Thus, the domain-specific interaction between usherin and type
      IV collagen appears essential to usherin stability in vivo, and loss of this
      interaction may result in Usher pathology in humans.

PMID- 14676277
TI  - Rac2D57N, a dominant inhibitory Rac2 mutant that inhibits p38 kinase signaling
      and prevents surface ruffling in bone-marrow-derived macrophages.
AB  - Rac2 is a Rho GTPase that is expressed in cells of hematopoietic origin,
      including neutrophils and macrophages. We recently described an immunodeficient
      patient with severe, recurrent bacterial infections that had a point mutation in
      one allele of the Rac2 gene, resulting in the substitution of aspartate 57 with
      asparagine. To ascertain further the effects of Rac2D57N in leukocytes, Rac2D57N
      was expressed in primary murine bone-marrow-derived macrophages (cells that we
      show express approximately equal amounts of Rac1 and Rac2). Rac2D57N expression
      in macrophages inhibited membrane ruffling. Rac2D57N expression inhibited the
      formation of macropinosomes, demonstrating a functional effect of the loss of
      surface membrane dynamics. Surprisingly, Rac2D57N induced an elongated, spread
      morphology but did not affect microtubule networks. Rac2D57N also inhibited
      lipopolysaccharide-stimulated p38 kinase activation. Examination of guanine
      nucleotide binding to recombinant Rac2D57N revealed reduced dissociation of GDP
      and association of GTP. Coimmunoprecipitation studies of Rac2D57N with RhoGDI
      alpha and Tiam1 demonstrated increased binding of Rac2D57N to these upstream
      regulators of Rac signaling relative to the wild type. Enhanced binding of
      Rac2D57N to its upstream regulators would inhibit Rac-dependent effects on actin
      cytoskeletal dynamics and p38 kinase signaling.

PMID- 14676278
TI  - A role for the cytoskeleton in prolactin-dependent mammary epithelial cell
      differentiation.
AB  - The function of exocrine glands depends on signals within the extracellular
      environment. In the mammary gland, integrin-mediated adhesion to the
      extracellular matrix protein laminin co-operates with soluble factors such as
      prolactin to regulate tissue-specific gene expression. The mechanism of matrix
      and prolactin crosstalk and the activation of downstream signals are not fully
      understood. Because integrins organize the cytoskeleton, we analysed the
      contribution of the cytoskeleton to prolactin receptor activation and the
      resultant stimulation of milk protein gene expression. We show that the proximal
      signalling events initiated by prolactin (i.e. tyrosine phosphorylation of
      receptor and the associated kinase Jak2) do not depend on an intact actin
      cytoskeleton. However, actin networks and microtubules are both necessary for
      continued mammary cell differentiation, because cytoskeletal integrity is
      required to transduce the signals between prolactin receptor and Stat5, a
      transcription factor necessary for milk protein gene transcription. The two
      different cytoskeletal scaffolds regulate prolactin signalling through separate
      mechanisms that are specific to cellular differentiation but do not affect the
      general profile of protein synthesis.

PMID- 14676279
TI  - Differential response of p53 target genes to p73 overexpression in SH-SY5Y
      neuroblastoma cell line.
AB  - p73, the first p53 gene homologue, encodes an array of p73 proteins including p73
      alpha full-length (TAp73 alpha) and amino-truncated isoforms (Delta Np73 alpha),
      two proteins with opposite biological functions. TAp73 alpha can induce tumor
      suppressive properties, while Delta Np73 alpha antagonizes p53 as well as TAp73
      in a dominant-negative manner. In human malignant neuroblasts, p53 protein is
      wild-type but known to be excluded from the nucleus, therefore disabling its
      function as a tumor suppressor. The present study investigates whether there is a
      functional link between p73 isoforms and p53 in neuroblastoma. Experiments were
      performed on two neuroblastoma cell lines differing in their p53 status, e.g.
      wild-type p53 SH-5Y5Y cells and mutated p53 IGR-N-91 cells. Data indicate that
      (i) both TA- and Delta N-p73 alpha enhance p53 protein level in SH-SY5Y cells,
      whereas level remains unchanged in IGR-N-91 cells; (ii) only in SH-SY5Y cells
      does forced TAp73 alpha overexpression markedly induce nuclear accumulation of
      p53 protein; (iii) p21 protein expression is increased in both cell lines
      infected with TAp73, suggesting that, in IGR-N-91 cells, p21 is induced by p73
      through a p53-independent pathway; (iv) in the SHSY5Y cell line, Btg2 expression
      is strongly enhanced in cells overexpressing TA, and to a lesser extent in cells
      overexpressing Delta N. Taken together our results suggest that TAp73 may restore
      p53 function in NB with wild-type nonfunctional p53, but not in NB with mutated
      p53.

PMID- 14676280
TI  - Mutations in alpha-tubulin promote basal body maturation and flagellar assembly
      in the absence of delta-tubulin.
AB  - We have isolated suppressors of the deletion allele of delta-tubulin, uni3-1, in
      the biflagellate green alga Chlamydomonas reinhardtii. The deletion of delta
      tubulin produces cells that assemble zero, one or two flagella and have basal
      bodies composed primarily of doublet rather than triplet microtubules. Flagellar
      number is completely restored in the suppressed strains. Most of the uni3-1
      suppressors map to the TUA2 locus, which encodes alpha2-tubulin. Twelve
      independent tua2 mutations were sequenced. Amino acids D205 or A208, which are
      nearly invariant residues in alpha-tubulin, were altered. The tua2 mutations on
      their own have a second phenotype - they make the cells colchicine
      supersensitive. Colchicine supersensitivity itself is not needed for suppression
      and colchicine cannot phenocopy the suppression. The suppressors partially
      restore the assembly of triplet microtubules. These results suggest that the
      delta-tubulin plays two roles: it is needed for extension or stability of the
      triplet microtubule and also for early maturation of basal bodies. We suggest
      that the mutant alpha-tubulin promotes the early maturation of the basal body in
      the absence of delta-tubulin, perhaps through interactions with other partners,
      and this allows assembly of the flagella.

PMID- 14676281
TI  - Ontogeny, immunolocalisation, distribution and function of SR-BI in the human
      intestine.
AB  - Studies employing human fetal intestine have yielded remarkable information on
      the role of polarized enterocytes in fat absorption. In this report, we
      investigated the intestinal expression, spatiotemporal distributions, ontogeny
      and function of the scavenger receptor, Class B, Type I (SR-BI) that plays a
      crucial role in cholesterol homeostasis. SR-BI was detected as early as week 14
      of gestation in all gut segments and was almost entirely confined to the
      absorptive epithelial cells. By using immunofluorescence staining, the
      distribution of SR-BI rarely appeared as a gradient, increasing from the
      developing crypt to the tip of the villus. Western blot showed high levels of
      immunodetectable SR-BI in the duodenum, which progressively decreased toward the
      distal colon. The high-resolution immunogold technique revealed labelling mainly
      over microvilli of the enterocyte. SR-BI was not associated with caveolin-1 and
      was not detectable in caveolae. In order to define the role of SR-BI in
      intestinal cholesterol absorption, Caco-2 cells were transfected with a
      constitutive expression vector (pZeoSV) containing human SR-BI cDNA inserted in
      an antisense orientation. As noted by immunoblotting and Protein A-gold
      techniques, stable transformants contained 40, 60 and 80% the SR-BI level of
      control Caco-2 cells and exhibited a proportional drop in free cholesterol uptake
      without altering the capture of phospholipids or cholesteryl ester. Confirmation
      of these data was obtained in intestinal organ culture where SR-BI antibodies
      lowered cholesterol uptake. These observations suggest that the human intestine
      possesses a developmental and regional SR-BI pattern of distribution, and extends
      our knowledge in SR-BI-mediated cholesterol transport.

PMID- 14676282
TI  - Activity of recycling Golgi mannosyltransferases in the yeast endoplasmic
      reticulum.
AB  - In yeast primary N- and O-glycans are attached to proteins in the endoplasmic
      reticulum (ER), and they are elongated in the Golgi. Thus, glycan extension by
      Golgi enzymes has been taken as evidence for arrival of a protein in the Golgi.
      Two alpha 1,6-mannosyltransferase activity-containing multiprotein complexes have
      been reported to recycle between the Golgi and the ER, but since resident ER
      proteins are not Golgi-modified, Golgi enzymes were not thought to function in
      the ER. Here we show that when protein exit from the ER was blocked in COPII
      defective yeast mutants, the N-glycans of vacuolar carboxypeptidase Y and a set
      of unidentified glycoproteins were decorated with an alpha 1,6-mannose residue,
      normally added in the Golgi by Och1p. Immunofluorescent staining demonstrated
      that Och1p accumulated in the ER under these conditions. Concomitantly, primary O
      glycans of a secretory protein were extended, apparently by the medial Golgi
      transferase Mnt1p. Similar O-glycan extension occurred in wild-type cells when an
      HDEL-tagged protein was allowed to encounter glycosyltransferases in the Golgi
      during recycling between ER and Golgi. Golgi-specific glycosylation in the ER was
      reduced when Golgi-to-ER traffic was blocked, confirming that glycan extension in
      the ER was mainly due to recycling, rather than newly synthesized transferases.

PMID- 14676283
TI  - Voltage-dependent Ca2+ fluxes in skeletal myotubes determined using a removal
      model analysis.
AB  - The purpose of this study was to quantify the Ca2+ fluxes underlying Ca2+
      transients and their voltage dependence in myotubes by using the "removal model
      fit" approach. Myotubes obtained from the mouse C2C12 muscle cell line were
      voltage-clamped and loaded with a solution containing the fluorescent indicator
      dye fura-2 (200 microM) and a high concentration of EGTA (15 mM). Ca2+ inward
      currents and intracellular ratiometric fluorescence transients were recorded in
      parallel. The decaying phases of Ca2+-dependent fluorescence signals after
      repolarization were fitted by theoretical curves obtained from a model that
      included the indicator dye, a slow Ca2+ buffer (to represent EGTA), and a
      sequestration mechanism as Ca2+ removal components. For each cell, the rate
      constants of slow buffer and transport and the off rate constant of fura-2 were
      determined in the fit. The resulting characterization of the removal properties
      was used to extract the Ca2+ input fluxes from the measured Ca2+ transients
      during depolarizing pulses. In most experiments, intracellular Ca2+ release
      dominated the Ca2+ input flux. In these experiments, the Ca2+ flux was
      characterized by an initial peak followed by a lower tonic phase. The voltage
      dependence of peak and tonic phase could be described by sigmoidal curves that
      reached half-maximal activation at -16 and -20 mV, respectively, compared with -2
      mV for the activation of Ca2+ conductance. The ratio of the peak to tonic phase
      (flux ratio) showed a gradual increase with voltage as in rat muscle fibers
      indicating the similarity to EC coupling in mature mammalian muscle. In a
      subgroup of myotubes exhibiting small fluorescence signals and in cells treated
      with 30 microM of the SERCA pump inhibitor cyclopiazonic acid (CPA) and 10 mM
      caffeine, the calculated Ca2+ input flux closely resembled the L-type Ca2+
      current, consistent with the absence of SR Ca2+ release under these conditions
      and in support of a valid determination of the time course of myoplasmic Ca2+
      input flux based on the optical indicator measurements.

PMID- 14676284
TI  - S4 movement in a mammalian HCN channel.
AB  - Hyperpolarization-activated, cyclic nucleotide-gated ion channels (HCN) mediate
      an inward cation current that contributes to spontaneous rhythmic firing activity
      in the heart and the brain. HCN channels share sequence homology with
      depolarization-activated Kv channels, including six transmembrane domains and a
      positively charged S4 segment. S4 has been shown to function as the voltage
      sensor and to undergo a voltage-dependent movement in the Shaker K+ channel (a Kv
      channel) and in the spHCN channel (an HCN channel from sea urchin). However, it
      is still unknown whether S4 undergoes a similar movement in mammalian HCN
      channels. In this study, we used cysteine accessibility to determine whether
      there is voltage-dependent S4 movement in a mammalian HCN1 channel. Six cysteine
      mutations (R247C, T249C, I251C, S253C, L254C, and S261C) were used to assess S4
      movement of the heterologously expressed HCN1 channel in Xenopus oocytes. We
      found a state-dependent accessibility for four S4 residues: T249C and S253C from
      the extracellular solution, and L254C and S261C from the internal solution. We
      conclude that S4 moves in a voltage-dependent manner in HCN1 channels, similar to
      its movement in the spHCN channel. This S4 movement suggests that the role of S4
      as a voltage sensor is conserved in HCN channels. In addition, to determine the
      reason for the different cAMP modulation and the different voltage range of
      activation in spHCN channels compared with HCN1 channels, we constructed a COOH
      terminal-deleted spHCN. This channel appeared to be similar to a COOH-terminal
      deleted HCN1 channel, suggesting that the main functional differences between
      spHCN and HCN1 channels are due to differences in their COOH termini or in the
      interaction between the COOH terminus and the rest of the channel protein in
      spHCN channels compared with HCN1 channels.

PMID- 14676285
TI  - Changes in local S4 environment provide a voltage-sensing mechanism for mammalian
      hyperpolarization-activated HCN channels.
AB  - The positively charged S4 transmembrane segment of voltage-gated channels is
      thought to function as the voltage sensor by moving charge through the membrane
      electric field in response to depolarization. Here we studied S4 movements in the
      mammalian HCN pacemaker channels. Unlike most voltage-gated channel family
      members that are activated by depolarization, HCN channels are activated by
      hyperpolarization. We determined the reactivity of the charged sulfhydryl
      modifying reagent, MTSET, with substituted cysteine (Cys) residues along the HCN1
      S4 segment. Using an HCN1 channel engineered to be MTS resistant except for the
      chosen S4 Cys substitution, we determined the reactivity of 12 S4 residues to
      external or internal MTSET application in either the closed or open state of the
      channel. Cys substitutions in the NH2-terminal half of S4 only reacted with
      external MTSET; the rates of reactivity were rapid, regardless of whether the
      channel was open or closed. In contrast, Cys substitutions in the COOH-terminal
      half of S4 selectively reacted with internal MTSET when the channel was open. In
      the open state, the boundary between externally and internally accessible
      residues was remarkably narrow (approximately 3 residues). This suggests that S4
      lies in a water-filled gating canal with a very narrow barrier between the
      external and internal solutions, similar to depolarization-gated channels.
      However, the pattern of reactivity is incompatible with either classical gating
      models, which postulate a large translational or rotational movement of S4 within
      a gating canal, or with a recent model in which S4 forms a peripheral voltage
      sensing paddle (with S3b) that moves within the lipid bilayer (the KvAP model).
      Rather, we suggest that voltage sensing is due to a rearrangement in
      transmembrane segments surrounding S4, leading to a collapse of an internal
      gating canal upon channel closure that alters the shape of the membrane field
      around a relatively static S4 segment.

PMID- 14676287
TI  - LEC1, FUS3, ABI3 and Em expression reveals no correlation with dormancy in
      Arabidopsis.
AB  - Dormant Arabidopsis seeds require stratification and light for germination. To
      study gene expression during establishment, maintenance and release of dormancy,
      various Arabidopsis ecotypes that are different in their degree of dormancy were
      investigated; three nsm mutants that lack the stratification-dependency, and the
      precocious germination and reduced dormancy of the abi3-1 mutant (insensitive to
      ABA). Genes examined by mRNA abundance include LEC1, FUS3 and ABI3, transcription
      factors that are major regulators of embryo development and, at least indirectly,
      play some role in the control of dormancy. Moreover, the late embryogenesis
      marker genes, AtEm1 and AtEm6, were examined in relation to the state of
      dormancy. The expression of LEC1, FUS3 and ABI3 mRNA is only marginally different
      during seed development in various strong or moderate dormancy wild types, nsm
      mutants and abi3-1. Therefore, it is unlikely that these transcription factors
      directly control the establishment of dormancy in Arabidopsis. Sole and various
      combina tions of light, temperature, and after-ripening regimes that alter
      germination behaviour were examined to determine if the expression of ABI3, AtEm1
      and AtEm6 mRNAs were correlated with dormancy-breaking processes. ABI3 expression
      is influenced by cold and light, in a similar way in both dormant and non-dormant
      wild-type seeds. ABI3 transcript abundance in the nsm1 and nsm2 mutants is higher
      and in the nsm5-1 mutant is marginally lower than in wild-type seeds, but changes
      due to temperature and light factors are very similar to those that occur in wild
      type seeds. The abundances of AtEm1 and AtEm6 mRNAs are equally affected by
      imbibition and cold temperature in mature and after-ripened seeds. The LEA
      transcript abundances for AtEm1 and AtEm6 are reduced in nsm mutants in a common,
      ABI3-independent pathway.

PMID- 14676286
TI  - How S4 segments move charge. Let me count the ways.

PMID- 14676288
TI  - Nodule-enhanced protease inhibitor gene: emerging patterns of gene expression in
      nodule development on Sesbania rostrata.
AB  - A novel marker for the early stages of nodulation of Sesbania rostrata was found
      to encode a putative member of the Kunitz family of protease inhibitors (SrPI1).
      Its expression was enhanced during nodulation, and was not up-regulated by
      wounding or upon infection with wide host-range pathogens. In situ expression
      patterns resembled those previously described for functions that may be
      implicated in delimiting infected nodule tissues from the rest of the plant.
      Thus, SrPI1 may be a component of a multi-layered barrier that restrains the
      invading rhizobia.

PMID- 14676289
TI  - Abscisic acid in the thermoinhibition of lettuce seed germination and enhancement
      of its catabolism by gibberellin.
AB  - Germination of lettuce (Lactuca sativa L. cv. 'Grand Rapids') seeds was inhibited
      at high temperatures (thermoinhibition). Thermoinhibition at 28 degrees C was
      prevented by the application of fluridone, an inhibitor of abscisic acid (ABA)
      biosynthesis. At 33 degrees C, the sensitivity of the seeds to ABA increased, and
      fluridone on its own was no longer effective. However, a combined application of
      fluridone and gibberellic acid (GA3) was able to restore the germination.
      Exogenous GA3 lowered endogenous ABA content in the seeds, enhancing catabolism
      of ABA and export of the catabolites from the intact seeds. The fluridone
      application also decreased the ABA content. Consequently, the combined
      application of fluridone and GA3 decreased the ABA content to a sufficiently low
      level to allow germination at 33 degrees C. There was no significant temperature
      dependent change in endogenous GA1 contents. It is concluded that ABA is an
      important factor in the regulation of thermoinhibition of lettuce seed
      germination, and that GA affects the temperature responsiveness of the seeds
      through ABA metabolism.

PMID- 14676290
TI  - Location and effects of long-term NaCl stress on superoxide dismutase and
      ascorbate peroxidase isoenzymes of pea (Pisum sativum cv. Puget) chloroplasts.
AB  - The present work describes the intrachloroplast localization and the changes that
      took place in the thylakoid and stroma-located superoxide dismutases (SOD, EC
      1.15.1.1) and ascorbate peroxidases (APX, EC 1.11.1.11), in response to long-term
      NaCl stress in Pisum sativum L. cv. Puget plants. Native PAGE using high
      chloroplast protein concentrations pointed to the presence of the two main Fe
      SODs, together with CuZn-SODs, both in thylakoids and in the stroma. Western blot
      and immunogold labelling using the antibodies against chloroplastic Fe-SOD from
      Nuphar luteum also confirmed the chloroplastic localization of a Fe-SOD.
      Thylakoidal Fe-SOD activity was induced by a NaCl concentration as low as 70 mM,
      while CuZn-SOD was induced at 90 mM, although in severe stress conditions (110
      mM) both activities were similar to the levels at 90 mM NaCl. NaCl stress also
      induced stromatic Fe-SOD and CuZn-SOD activities, although these inductions only
      started at higher NaCl concentration (90 mM) and were significant at 110 mM NaCl.
      The increase in activity of both Fe-SODs was matched by an increase in Fe-SOD
      protein. Chloroplastic APX isoenzymes behaved differently in thylakoids and
      stroma in response to NaCl. A significant increase of stromal APX occurred at 70
      mM, whereas the thylakoidal APX activity was significantly and progressively lost
      in response to NaCl stress (70-110 mM). A significant increase in the H2O2
      content of chloroplasts during stress and a reduction in the ascorbate level at
      90 mM NaCl also took place, although the oxidized ascorbate pool at the highest
      NaCl concentration did not show significant changes. These results suggest that
      the loss of thylakoidal APX may be an important factor in the increase in
      chloroplastic H2O2, which also results from the increased thylakoid and stroma
      located Fe-SOD and CuZn-SOD activities. This H2O2 may be involved in the
      induction of stromal APX. The up-regulation of the above enzymes in the described
      stress conditions would contribute to the adaptation of cv. Puget plants to
      moderate NaCl stress.

PMID- 14676291
TI  - Immunosuppressive and proinflammatory activities of the VacA toxin of
      Helicobacter pylori.

PMID- 14676292
TI  - Progress in defining CD4 helper cell responses in chronic viral infections.

PMID- 14676293
TI  - Invariant NKT cells as initiators, licensors, and facilitators of the adaptive
      immune response.

PMID- 14676294
TI  - Cutaneous immunization rapidly activates liver invariant Valpha14 NKT cells
      stimulating B-1 B cells to initiate T cell recruitment for elicitation of contact
      sensitivity.
AB  - T cell recruitment to elicit contact sensitivity (CS) requires a CS-initiating
      process mediated by B-1 cells that produce IgM, which activates complement to
      promote T cell passage into the tissues. We now show that Valpha14i NKT cells
      induce B-1 cell activation likely by releasing IL-4 early postimmunization. The
      CS initiation process is absent in Jalpha18-/- and CD1d-/- NKT cell-deficient
      mice and is reconstituted by populations enriched for Valpha14i NKT cells.
      Transfers are not effective if cells are derived from IL-4-/- mice. Staining with
      specific tetramers directly showed that hepatic Valpha14i NKT cells increase by
      30 min and nearly double by 2 h postimmunization. Transfer of immune B-1 cells
      also reconstitutes CS responses in NKT cell-deficient mice. The B-1 cells act
      downstream of the Valpha14i NKT cells to restore CS initiation. In addition, IL-4
      given systemically to Jalpha18-/- or CD1d-/- NKT cell-deficient mice
      reconstitutes elicitation of CS. Further, splenocytes from immune Jalpha18-/-
      mice produce less antigen (Ag)-specific IgM antibodies compared with sensitized
      WT mice. Together these findings indicate that very early after skin immunization
      Valpha14i NKT cells are stimulated to produce IL-4, which activates B-1 cells to
      produce Ag-specific IgM, subsequently needed to recruit effector T cells for
      elicitation of CS responses.

PMID- 14676295
TI  - IL-7 promotes the transition of CD4 effectors to persistent memory cells.
AB  - After transfer to adoptive hosts, in vitro-generated CD4 effectors can become
      long-lived memory cells, but the factors regulating this transition are unknown.
      We find that low doses of interleukin (IL) 7 enhance survival of effectors in
      vitro without driving their division. When in vitro-generated effectors are
      transferred to normal intact adoptive hosts, they survive and rapidly become
      small resting cells with a memory phenotype. CD4 effectors generated from wild
      type versus IL-7 receptor-/- mice were transferred to adoptive hosts, including
      intact mice and those deficient in IL-7. In each case, the response to IL-7 was
      critical for good recovery of donor cells after 5-7 d. Recovery was also IL-7
      dependent in Class II hosts where division was minimal. Blocking antibodies to IL
      7 dramatically decreased short-term recovery of transferred effectors in vivo
      without affecting their division. These data indicate that IL-7 plays a critical
      role in promoting memory CD4 T cell generation by providing survival signals,
      which allow effectors to successfully become resting memory cells.

PMID- 14676296
TI  - Activation of transforming growth factor beta by malaria parasite-derived
      metalloproteinases and a thrombospondin-like molecule.
AB  - Much of the pathology of malaria is mediated by inflammatory cytokines (such as
      interleukin 12, interferon gamma, and tumor necrosis factor alpha), which are
      part of the immune response that kills the parasite. The antiinflammatory
      cytokine transforming growth factor (TGF)-beta plays a crucial role in preventing
      the severe pathology of malaria in mice and TGF-beta production is associated
      with reduced risk of clinical malaria in humans. Here we show that serum-free
      preparations of Plasmodium falciparum, Plasmodium yoelii 17XL, and Plasmodium
      berghei schizont-infected erythrocytes, but not equivalent preparations of
      uninfected erythrocytes, are directly able to activate latent TGF-beta (LatTGF
      beta) in vitro. Antibodies to thrombospondin (TSP) and to a P. falciparum TSP
      related adhesive protein (PfTRAP), and synthetic peptides from PfTRAP and P.
      berghei TRAP that represent homologues of TGF-beta binding motifs of TSP, all
      inhibit malaria-mediated TGF-beta activation. Importantly, TRAP-deficient P.
      berghei parasites are less able to activate LatTGF-beta than wild-type parasites
      and their replication is attenuated in vitro. We show that activation of TGF-beta
      by malaria parasites is a two step process involving TSP-like molecules and
      metalloproteinase activity. Activation of LatTGF-beta represents a novel
      mechanism for direct modulation of the host response by malaria parasites.

PMID- 14676297
TI  - CD226 (DNAM-1) is involved in lymphocyte function-associated antigen 1
      costimulatory signal for naive T cell differentiation and proliferation.
AB  - Upon antigen recognition by the T cell receptor, lymphocyte function-associated
      antigen 1 (LFA-1) physically associates with the leukocyte adhesion molecule
      CD226 (DNAM-1) and the protein tyrosine kinase Fyn. We show that lentiviral
      vector-mediated mutant (Y-F322) CD226 transferred into naive CD4+ helper T cells
      (Ths) inhibited interleukin (IL)-12-independent Th1 development initiated by CD3
      and LFA-1 ligations. Moreover, proliferation induced by LFA-1 costimulatory
      signal was suppressed in mutant (Y-F322) CD226-transduced naive CD4+ and CD8+ T
      cells in the absence of IL-2. These results suggest that CD226 is involved in LFA
      1-mediated costimulatory signals for triggering naive T cell differentiation and
      proliferation. We also demonstrate that although LFA-1, CD226, and Fyn are
      polarized at the immunological synapse upon stimulation with anti-CD3 in CD4+ and
      CD8+ T cells, lipid rafts are polarized in CD4+, but not CD8+, T cells. Moreover,
      proliferation initiated by LFA-1 costimulatory signal is suppressed by lipid raft
      disruption in CD4+, but not CD8+, T cells, suggesting that the LFA-1
      costimulatory signal is independent of lipid rafts in CD8+ T cells.

PMID- 14676298
TI  - Requirement for Ras guanine nucleotide releasing protein 3 in coupling
      phospholipase C-gamma2 to Ras in B cell receptor signaling.
AB  - Two important Ras guanine nucleotide exchange factors, Son of sevenless (Sos) and
      Ras guanine nucleotide releasing protein (RasGRP), have been implicated in
      controlling Ras activation when cell surface receptors are stimulated. To address
      the specificity or redundancy of these exchange factors, we have generated
      Sos1/Sos2 double- or RasGRP3-deficient B cell lines and determined their ability
      to mediate Ras activation upon B cell receptor (BCR) stimulation. The BCR
      requires RasGRP3; in contrast, epidermal growth factor receptor is dependent on
      Sos1 and Sos2. Furthermore, we show that BCR-induced recruitment of RasGRP3 to
      the membrane and the subsequent Ras activation are significantly attenuated in
      phospholipase C-gamma2-deficient B cells. This defective Ras activation is
      suppressed by the expression of RasGRP3 as a membrane-attached form, suggesting
      that phospholipase C-gamma2 regulates RasGRP3 localization and thereby Ras
      activation.

PMID- 14676299
TI  - Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells
      by TGF-beta induction of transcription factor Foxp3.
AB  - CD4+CD25+ regulatory T cells (Treg) are instrumental in the maintenance of
      immunological tolerance. One critical question is whether Treg can only be
      generated in the thymus or can differentiate from peripheral CD4+CD25- naive T
      cells. In this paper, we present novel evidence that conversion of naive
      peripheral CD4+CD25- T cells into anergic/suppressor cells that are CD25+, CD45RB
      /low and intracellular CTLA-4+ can be achieved through costimulation with T cell
      receptors (TCRs) and transforming growth factor beta (TGF-beta). Although
      transcription factor Foxp3 has been shown recently to be associated with the
      development of Treg, the physiological inducers for Foxp3 gene expression remain
      a mystery. TGF-beta induced Foxp3 gene expression in TCR-challenged CD4+CD25-
      naive T cells, which mediated their transition toward a regulatory T cell
      phenotype with potent immunosuppressive potential. These converted
      anergic/suppressor cells are not only unresponsive to TCR stimulation and produce
      neither T helper cell 1 nor T helper cell 2 cytokines but they also express TGF
      beta and inhibit normal T cell proliferation in vitro. More importantly, in an
      ovalbumin peptide TCR transgenic adoptive transfer model, TGF-beta-converted
      transgenic CD4+CD25+ suppressor cells proliferated in response to immunization
      and inhibited antigen-specific naive CD4+ T cell expansion in vivo. Finally, in a
      murine asthma model, coadministration of these TGF-beta-induced suppressor T
      cells prevented house dust mite-induced allergic pathogenesis in lungs.

PMID- 14676300
TI  - The Helicobacter pylori vacuolating toxin inhibits T cell activation by two
      independent mechanisms.
AB  - Helicobacter pylori toxin, VacA, damages the gastric epithelium by erosion and
      loosening of tight junctions. Here we report that VacA also interferes with T
      cell activation by two different mechanisms. Formation of anion-specific channels
      by VacA prevents calcium influx from the extracellular milieu. The transcription
      factor NF-AT thus fails to translocate to the nucleus and activate key cytokine
      genes. A second, channel-independent mechanism involves activation of
      intracellular signaling through the mitogen-activated protein kinases MKK3/6 and
      p38 and the Rac-specific nucleotide exchange factor, Vav. As a consequence of
      aberrant Rac activation, disordered actin polymerization is stimulated. The
      resulting defects in T cell activation may help H. pylori to prevent an effective
      immune response leading to chronic colonization of its gastric niche.

PMID- 14676301
TI  - Abnormal mammary gland development and growth retardation in female mice and MCF7
      breast cancer cells lacking androgen receptor.
AB  - Phenotype analysis of female mice lacking androgen receptor (AR) deficient (AR-/
      ) indicates that the development of mammary glands is retarded with reduced
      ductal branching in the prepubertal stages, and fewer Cap cells in the terminal
      end buds, as well as decreased lobuloalveolar development in adult females, and
      fewer milk-producing alveoli in the lactating glands. The defective development
      of AR-/- mammary glands involves the defects of insulin-like growth factor I
      insulin-like growth factor I receptor and mitogen-activated protein kinase (MAPK)
      signals as well as estrogen receptor (ER) activity. Similar growth retardation
      and defects in growth factor-mediated Ras/Raf/MAPK cascade and ER signaling are
      also found in AR-/- MCF7 breast cancer cells. The restoration assays show that AR
      NH2-terminal/DNA-binding domain, but not the ligand-binding domain, is essential
      for normal MAPK function in MCF7 cells, and an AR mutant (R608K), found in male
      breast cancer, is associated with the excessive activation of MAPK. Together, our
      data provide the first in vivo evidence showing that AR-mediated MAPK and ER
      activation may play important roles for mammary gland development and MCF7 breast
      cancer cell proliferation.

PMID- 14676302
TI  - HIV-1 viremia prevents the establishment of interleukin 2-producing HIV-specific
      memory CD4+ T cells endowed with proliferative capacity.
AB  - CD4+ T cell responses are associated with disease control in chronic viral
      infections. We analyzed human immunodeficiency virus (HIV)-specific responses in
      ten aviremic and eight viremic patients treated during primary HIV-1 infection
      and for up to 6 yr thereafter. Using a highly sensitive 5-(and-6)
      carboxyfluorescein diacetate-succinimidyl ester-based proliferation assay, we
      observed that proliferative Gag and Nef peptide-specific CD4+ T cell responses
      were 30-fold higher in the aviremic patients. Two subsets of HIV-specific memory
      CD4+ T cells were identified in aviremic patients, CD45RA- CCR7+ central memory
      cells (Tcm) producing exclusively interleukin (IL)-2, and CD45RA- CCR7- effector
      memory cells (Tem) that produced both IL-2 and interferon (IFN)-gamma. In
      contrast, in viremic, therapy-failing patients, we found significant frequencies
      of Tem that unexpectedly produced exclusively IFN-gamma. Longitudinal analysis of
      HIV epitope-specific CD4+ T cells revealed that only cells that had the capacity
      to produce IL-2 persisted as long-term memory cells. In viremic patients the
      presence of IFN-gamma-producing cells was restricted to periods of elevated
      viremia. These findings suggest that long-term CD4+ T cell memory depends on IL-2
      producing CD4+ T cells and that IFN-gamma only-producing cells are short lived.
      Our data favor a model whereby competent HIV-specific Tcm continuously arise in
      small numbers but under persistent antigenemia are rapidly induced to
      differentiate into IFN-gamma only-producing cells that lack self-renewal
      capacity.

PMID- 14676303
TI  - The role of Brg1, a catalytic subunit of mammalian chromatin-remodeling
      complexes, in T cell development.
AB  - Mammalian SWI-SNF-related complexes use brahma-related gene 1 (Brg1) as a
      catalytic subunit to remodel nucleosomes and regulate transcription. Recent
      biochemical data has linked Brg1 function to genes important for T lymphocyte
      differentiation. To investigate the role of SWI-SNF-related complexes in this
      lineage, we ablated Brg1 function in T lymphocytes. T cell-specific Brg1
      deficient mice showed profound thymic abnormalities, CD4 derepression at the
      double negative (DN; CD4- CD8-) stage, and a developmental block at the DN to
      double positive (CD4+ CD8+) transition. 5'-bromo-2'-deoxyuridine incorporation
      and annexin V staining establish a role for Brg1 complexes in the regulation of
      thymocyte cell proliferation and survival. This Brg1-dependent cell survival is
      specific for developing thymocytes as indicated by the presence of Brg1-deficient
      mature T lymphocytes that have escaped the developmental block in the thymus.
      However, reductions in peripheral T cell populations lead to immunodeficiency and
      compromised health of mutant mice. These results highlight the importance of
      chromatin-remodeling complexes at different stages in the development of a
      mammalian cell lineage.

PMID- 14676304
TI  - The tumor suppressor CYLD interacts with TRIP and regulates negatively nuclear
      factor kappaB activation by tumor necrosis factor.
AB  - Cylindromas are benign adnexal skin tumors caused by germline mutations in the
      CYLD gene. In most cases the second wild-type allele is lost in tumor tissue,
      suggesting that CYLD functions as tumor suppressor. CYLD is a protein of 956
      amino acids harboring a functional deubiquitinating domain at the COOH-terminal
      end. To shed more light on the function of CYLD, we have performed a yeast two
      hybrid screen using an HaCaT cDNA library that identified the RING finger protein
      TRIP (TRAF-interacting protein) as interactor with full-length CYLD. Mapping of
      the interacting domains revealed that the central domain of CYLD binds to the
      COOH-terminal end of TRIP. Far Western analysis and coimmunoprecipitations in
      mammalian cells confirmed that full-length CYLD binds to the COOH-terminal domain
      of TRIP. Because TRIP is an inhibitor of nuclear factor (NF)-kappaB activation by
      tumor necrosis factor (TNF), the effect of CYLD on NF-kappaB activation was
      investigated in HeLa cells. The results established that CYLD down-regulates NF
      kappaB activation by TNF-alpha. The inhibition by CYLD depends on the presence of
      the central domain interacting with TRIP and its deubiquitinating activity. These
      findings indicate that cylindromas arise through constitutive NF-kappaB
      activation leading to hyperproliferation and tumor growth.

PMID- 14676305
TI  - TGF-beta receptor kinase inhibitor enhances growth and integrity of embryonic
      stem cell-derived endothelial cells.
AB  - Recent findings have shown that embryonic vascular progenitor cells are capable
      of differentiating into mural and endothelial cells. However, the molecular
      mechanisms that regulate their differentiation, proliferation, and endothelial
      sheet formation remain to be elucidated. Here, we show that members of the
      transforming growth factor (TGF)-beta superfamily play important roles during
      differentiation of vascular progenitor cells derived from mouse embryonic stem
      cells (ESCs) and from 8.5-days postcoitum embryos. TGF-beta and activin inhibited
      proliferation and sheet formation of endothelial cells. Interestingly, SB-431542,
      a synthetic molecule that inhibits the kinases of receptors for TGF-beta and
      activin, facilitated proliferation and sheet formation of ESC-derived endothelial
      cells. Moreover, SB-431542 up-regulated the expression of claudin-5, an
      endothelial specific component of tight junctions. These results suggest that
      endogenous TGF-beta/activin signals play important roles in regulating vascular
      growth and permeability.

PMID- 14676306
TI  - PLA2 activity is required for nuclear shrinkage in caspase-independent cell
      death.
AB  - Apoptosis is defined on the basis of morphological changes like nuclear
      fragmentation and chromatin condensation, which are dependent on caspases. Many
      forms of caspase-independent cell death have been reported, but the mechanisms
      are still poorly understood. We found that hypoxic cell death was independent of
      caspases and was associated with significant nuclear shrinkage. Neither Bcl-2 nor
      Apaf-1 deficiency prevented hypoxic nuclear shrinkage. To understand the
      molecular mechanism of the nuclear shrinkage, we developed an in vitro system
      using permeabilized cells, which allowed us to purify a novel member of the
      phospholipase A2 (PLA2) family that induced nuclear shrinkage. Purified PLA2
      induced nuclear shrinkage in our permeabilized cell system. PLA2 inhibitors
      prevented hypoxic nuclear shrinkage in cells and cell death. Hypoxia caused
      elevation of PLA2 activity and translocation of intracellular PLA2s to the
      nucleus. Knockdown of the Ca2+-independent PLA2 delayed nuclear shrinkage and
      cell death. These results indicate that Ca2+-independent PLA2 is crucial for a
      caspase-independent cell death signaling pathway leading to nuclear shrinkage.

PMID- 14676307
TI  - Balancing different types of actin polymerization at distinct sites: roles for
      Abelson kinase and Enabled.
AB  - The proto-oncogenic kinase Abelson (Abl) regulates actin in response to cell
      signaling. Drosophila Abl is required in the nervous system, and also in
      epithelial cells, where it regulates adherens junction stability and actin
      organization. Abl acts at least in part via the actin regulator Enabled (Ena),
      but the mechanism by which Abl regulates Ena is unknown. We describe a novel role
      for Abl in early Drosophila development, where it regulates the site and type of
      actin structures produced. In Abl's absence, excess actin is polymerized in
      apical microvilli, whereas too little actin is assembled into pseudocleavage and
      cellularization furrows. These effects involve Ena misregulation. In abl mutants,
      Ena accumulates ectopically at the apical cortex where excess actin is observed,
      suggesting that Abl regulates Ena's subcellular localization. We also examined
      other actin regulators. Loss of Abl leads to changes in the localization of the
      Arp2/3 complex and the formin Diaphanous, and mutations in diaphanous or capping
      protein beta enhance abl phenotypes.

PMID- 14676309
TI  - Caspr regulates the processing of contactin and inhibits its binding to
      neurofascin.
AB  - Three cell adhesion molecules are present at the axoglial junctions that form
      between the axon and myelinating glia on either side of nodes of Ranvier. These
      include an axonal complex of contacin-associated protein (Caspr) and contactin,
      which was proposed to bind NF155, an isoform of neurofascin located on the glial
      paranodal loops. Here, we show that NF155 binds directly to contactin and that
      surprisingly, coexpression of Caspr inhibits this interaction. This inhibition
      reflects the association of Caspr with contactin during biosynthesis and the
      resulting expression of a low molecular weight (LMw), endoglycosidase H-sensitive
      isoform of contactin at the cell membrane, which remains associated with Caspr
      but is unable to bind NF155. Accordingly, deletion of Caspr in mice by gene
      targeting results in a shift from the LMw- to a HMw-contactin glycoform. These
      results demonstrate that Caspr regulates the intracellular processing and
      transport of contactin to the cell surface, thereby affecting its ability to
      interact with other cell adhesion molecules.

PMID- 14676308
TI  - Signal-dependent distribution of cell surface P-selectin in clathrin-coated pits
      affects leukocyte rolling under flow.
AB  - Flowing leukocytes roll on P-selectin that is mobilized from secretory granules
      to the surfaces of endothelial cells after stimulation with histamine or
      thrombin. Before it is internalized, P-selectin clusters in clathrin-coated pits,
      which enhances its ability to support leukocyte rolling. We found that thrombin
      and histamine induced comparable exocytosis of P-selectin on endothelial cells.
      However, compared with histamine, thrombin decreased the recruitment of P
      selectin into clathrin-coated pits, slowed the internalization of P-selectin, and
      reduced the number and stability of neutrophils rolling on P-selectin.
      Significantly more RhoA was activated in thrombin- than in histamine-stimulated
      endothelial cells. Inhibitors of RhoA or its effector, Rho kinase, reversed
      thrombin's ability to inhibit the internalization and adhesive function of P
      selectin in endothelial cells. Experiments with transfected cells confirmed that
      the inhibitory actions of thrombin and Rho kinase on P-selectin required its
      cytoplasmic domain. Thus, a signaling event affects both the function and
      clearance of a protein that enters the constitutive clathrin-mediated endocytic
      pathway.

PMID- 14676310
TI  - A new tool for routine testing of cellular protein expression: integration of
      cell staining and analysis of protein expression on a microfluidic chip-based
      system.
AB  - The key benefits of Lab-on-a-Chip technology are substantial time savings via an
      automation of lab processes, and a reduction in sample and reagent volumes
      required to perform analysis. In this article we present a new implementation of
      cell assays on disposable microfluidic chips. The applications are based on the
      controlled movement of cells by pressure-driven flow in microfluidic channels and
      two-color fluorescence detection of single cells. This new technology allows for
      simple flow cytometric studies of cells in a microfluidic chip-based system. In
      addition, we developed staining procedures that work "on-chip," thus eliminating
      time-consuming washing steps. Cells and staining-reagents are loaded directly
      onto the microfluidic chip and analysis can start after a short incubation time.
      These procedures require only a fraction of the staining reagents generally
      needed for flow cytometry and only 30,000 cells per sample, demonstrating the
      advantages of microfluidic technology. The specific advantage of an on-chip
      staining reaction is the amount of time, cells, and reagents saved, which is of
      great importance when working with limited numbers of cells, e.g., primary cells
      or when needing to perform routine tests of cell cultures as a quality control
      step. Applications of this technology are antibody staining of proteins and
      determination of cell transfection efficiency by GFP expression. Results obtained
      with microfluidic chips, using standard cell lines and primary cells, show good
      correlation with data obtained using a conventional flow cytometer.

PMID- 14676311
TI  - Differential proteome analysis: two-dimensional nano-LC/MS of E. coli proteome
      grown on different carbon sources.
AB  - Different sugars provided to bacteria as single sources of carbon and energy
      require the induction of different metabolic enzymes, transporters, and uptake
      systems in order to support growth and cell survival. Using a nano-high
      performance liquid chromatography/mass spectrometry (nano-HPLC/MS) system we
      constructed comprehensive peptide maps for Escherichia coli grown with either
      lactose or glucose in minimal medium. Digested bacterial samples were separated
      in a two-dimensional manner by combining strong cation exchange (SCX) and
      reversed-phased (RP) chromatography. Peptides were eluted online to an iontrap MS
      instrument and further analyzed by tandem MS fragmentation. Bacterial proteins
      originating from the differing samples were analyzed by searching the Swiss Prot
      Database. Data are presented that show the ability to detect several hundred
      different proteins significantly expressed under both conditions. Several enzymes
      and binding proteins related to the lactose metabolism were only identified in
      the sample grown with this carbon source.

PMID- 14676312
TI  - Mass-based fraction collection of crude synthetic peptides in analytical and
      preparative scale.
AB  - Synthetic peptides become more and more important as drug candidates in the
      treatment of a variety of diseases. A particular therapeutic focus for synthetic
      peptides is cancer treatment.1,2 In order to keep pace with the growing number of
      newly synthesized peptides, peptide purification should not represent the
      bottleneck in the drug discovery process. Since the target masses of synthetic
      peptides are well known, mass-based fraction collection represents an efficient
      technique for their purification. In contrast to fraction triggering with less
      specific detectors, employing a mass selective detector leads in each run only to
      the purification of the target mass. Consequently, it is not necessary to pick
      the compound of interest out of a series of redundant fractions. In this article
      we demonstrate mass-based purification of a variety of crude synthetic peptides
      by reversed phase high-performance liquid chromatography. The peptides were in
      the mass range from less than 1 kDa to more than 10 kDa and covered a pI range
      from 4 to 13. We particularly focused on some technical aspects of the system
      that were prerequisite for reliable compound purification with high recoveries.

PMID- 14676313
TI  - TempliPhi: A sequencing template preparation procedure that eliminates overnight
      cultures and DNA purification.
AB  - Preparing plasmid templates for DNA sequencing is the most time-consuming step in
      the sequencing process. Current template preparation methods rely on a labor
      intensive, multistep procedure that takes up to 24 h and produces templates of
      varying quality and quantity. The TempliPhi DNA Sequencing Template Amplification
      Kit eliminates the requirement for extended bacterial growth prior to sequencing
      and saves laboratory personnel hands-on time by eliminating the centrifugation
      and transfer steps currently required by older preparatory methods. In addition,
      costly purification filters and columns are not necessary, as amplified product
      can be added directly to a sequencing reaction. Starting material can be any
      circular template from a colony, culture, glycerol stock, or plaque. Based on
      rolling circle amplification and employing bacteriophage Phi29 DNA polymerase,
      the method can produce 3-5 microg of template directly from a single bacterial
      colony in as little as 4 h. Implementation of these procedures in a laboratory or
      core sequencing facility can decrease cost on tips, plates, and other
      plasticware, while at the same time increase throughput.

PMID- 14676314
TI  - High-throughput analysis of protein/peptide complexes by immunoprecipitation and
      automated LC-MS/MS.
AB  - BACKGROUND: The identification of interacting proteins within protein complexes
      is key to understanding the transduction and regulation of cell signaling
      pathways, and is also a useful tool for identifying novel disease markers.
      Immunoprecipitation of protein complexes followed by liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) has been used to identify targets that bind to a
      protein of interest. Here, we report a high-throughput nanoflow LC-MS/MS method
      for analysis of protein/peptide complexes. APPROACH: To overcome the large dwell
      volume from connecting lines and the injector when using an autosampler in
      microcapillary LC-MS/MS, we employed a valve-controlled variable flow method with
      a peptide trap. This method enables fast trapping of peptides from samples
      injected by an autosampler within minutes followed by a split-controlled nanoflow
      of acetonitrile gradient through a microcapillary C18 column to separate and
      elute peptides into the ion-trap MS/MS. Over 40 protein/peptide samples at
      femtomole levels could be analyzed continuously using the same in-house packed
      microcapillary C18 column. The p38 mitogen-activated protein kinase (p38 MAP
      kinase) is a signaling protein that is involved in transduction of extracellular
      signals including oxidative stress, growth factors, and cytokines, with diverse
      cellular consequences such as cell proliferation, differentiation, or apoptosis.
      Immunocomplex of monoclonal anti-p38 beta antibodies from 2 mg total lysates from
      the OCI LY-1 lymphoma cell line was resolved in 1D-PAGE gel followed by silver
      staining of the gel. Protein bands were excised and digested with trypsin.
      Peptides were extracted and analyzed using the automated LC-MS/MS method. RESULTS
      AND CONCLUSIONS: From 37 excised protein bands in the 1D-PAGE gel, we identified
      more than 50 proteins, including cytoskeletal proteins, ribosomal proteins,
      transcription factors, and KIAA potential signaling proteins. These proteins are
      the potential targets that may interact directly or indirectly with the p38 MAP
      kinase proteins. Our studies demonstrate the utility of automated nanoflow LC
      MS/MS for sensitive and high-throughput analysis of protein/peptide complexes.
      Utilization of methods based on this principle would greatly facilitate peptide
      interaction mapping and other proteomic studies requiring high-throughput pre
      analytical sample preparation.

PMID- 14676315
TI  - Gene expression analysis of plant host-pathogen interactions by SuperSAGE.
AB  - The type III restriction endonuclease EcoP15I was used in isolating fragments of
      26 bp from defined positions of cDNAs. We call this substantially improved
      variant to the conventional serial analysis of gene expression (SAGE) procedure
      "SuperSAGE." By applying SuperSAGE to Magnaporthe grisea (blast)-infected rice
      leaves, gene expression profiles of both the rice host and blast fungus were
      simultaneously monitored by making use of the fully sequenced genomes of both
      organisms, revealing that the hydrophobin gene is the most actively transcribed
      M. grisea gene in blast-infected rice leaves. Moreover, SuperSAGE was applied to
      study gene expression changes before the so-called hypersensitive response in
      INF1 elicitor-treated Nicotiana benthamiana, a "nonmodel" organism for which no
      DNA database is available. Again, SuperSAGE allowed rapid identification of genes
      up- or down-regulated by the elicitor. Surprisingly, many of the down-regulated
      genes coded for proteins involved in photosynthesis. SuperSAGE will be especially
      useful for transcriptome profiling of two or more interacting organisms like
      hosts and pathogens, and of organisms, for which no DNA database is available.

PMID- 14676316
TI  - Chemical chaperone therapy for brain pathology in G(M1)-gangliosidosis.
AB  - We synthesized a galactose derivative, N-octyl-4-epi-beta-valienamine (NOEV), for
      a molecular therapy (chemical chaperone therapy) of a human neurogenetic disease,
      beta-galactosidosis (GM1-gangliosidosis and Morquio B disease). It is a potent
      inhibitor of lysosomal beta-galactosidase in vitro. Addition of NOEV in the
      culture medium restored mutant enzyme activity in cultured human or murine
      fibroblasts at low intracellular concentrations, resulting in a marked decrease
      of intracellular substrate storage. Short-term oral administration of NOEV to a
      model mouse of juvenile GM1-gangliosidosis, expressing a mutant enzyme protein
      R201C, resulted in significant enhancement of the enzyme activity in the brain
      and other tissues. Immunohistochemical stain revealed a decrease in the amount of
      GM1 and GA1 in neuronal cells in the fronto-temporal cerebral cortex and
      brainstem. However, mass biochemical analysis did not show the substrate
      reduction observed histochemically in these limited areas in the brain probably
      because of the brief duration of this investigation. Chemical chaperone therapy
      may be useful for certain patients with beta-galactosidosis and potentially other
      lysosomal storage diseases with central nervous system involvement.

PMID- 14676317
TI  - Genetic, biochemical, and morphological evidence for the involvement of N
      glycosylation in biosynthesis of the cell wall beta1,6-glucan of Saccharomyces
      cerevisiae.
AB  - Recent evidence indicates that Stt3p plays a central role in the recognition
      and/or catalytic step in N-glycosylation (asparagine-linked glycosylation) in the
      lumen of the endoplasmic reticulum. It is known that stt3 mutants exhibit certain
      phenotypic features that are suggestive of a cell wall defect. To understand the
      basis of these phenotypes, we devised a genetic screen to isolate strains bearing
      mutations that lead to synthetic lethality in combination with the stt3-1
      mutation. Using this screen, we were surprised to identify two KRE genes (KRE5
      and KRE9) that are involved in the biosynthesis of the cell wall beta1,6-glucan.
      This finding led us to propose that the N-glycosylation process is essential in
      the biosynthesis of cell wall beta1,6-glucan. This proposal was supported by the
      observation that several stt3 mutants exhibited a 60-70% reduction in the content
      of cell wall beta1,6-glucan as compared with WT cells. Transmission electron
      microscopy revealed that the stt3 mutant strains exhibit a diffused cell wall
      with loss of the outer mannoprotein layer as compared with the WT cells. Thus, we
      provide genetic, morphological, and biochemical evidence for the critical
      involvement of N-glycosylation in some step in assembly of the cell wall beta1,6
      glucan in Saccharomyces cerevisiae.

PMID- 14676318
TI  - Prediction and statistics of pseudoknots in RNA structures using exactly
      clustered stochastic simulations.
AB  - Ab initio RNA secondary structure predictions have long dismissed helices
      interior to loops, so-called pseudoknots, despite their structural importance.
      Here we report that many pseudoknots can be predicted through long-time-scale RNA
      folding simulations, which follow the stochastic closing and opening of
      individual RNA helices. The numerical efficacy of these stochastic simulations
      relies on an O(n2) clustering algorithm that computes time averages over a
      continuously updated set of n reference structures. Applying this exact
      stochastic clustering approach, we typically obtain a 5- to 100-fold simulation
      speed-up for RNA sequences up to 400 bases, while the effective acceleration can
      be as high as 105-fold for short, multistable molecules (<or=150 bases). We
      performed extensive folding statistics on random and natural RNA sequences and
      found that pseudoknots are distributed unevenly among RNA structures and account
      for up to 30% of base pairs in G+C-rich RNA sequences (online RNA-folding
      kinetics server including pseudoknots: http://kinefold.u-strasbg.fr).

PMID- 14676319
TI  - Phylogenomic analysis of type I polyketide synthase genes in pathogenic and
      saprobic ascomycetes.
AB  - Fungal type I polyketides (PKs) are synthesized by PK synthases (PKSs) and
      include well known secondary metabolites such as the anticholesterol drug
      lovastatin and the potent natural carcinogen aflatoxin. Other type I PKs are
      known to be virulence factors for some plant pathogens and pigments such as
      melanin. In this study, a phylogenomic approach was used to investigate the
      origin and diversity of fungal genes encoding putative PKSs that are predicted to
      synthesize type I PKs. The resulting genealogy, constructed by using the highly
      conserved PKS ketosynthase (KS) domain, indicated that: (i). Species within
      subphylum Pezizomycotina (phylum Ascomycota) but not early diverging ascomycetes,
      like Saccharomyces cerevisiae (Saccharomycotina) or Schizosaccharomyces pombe
      (Taphrinomycotina), had large numbers (7-25) of PKS genes. (ii). Bacteria and
      fungi had separate groups of PKS genes; the few exceptions are the likely result
      of horizontal gene transfer from bacteria to various sublineages of fungi. (iii).
      The bulk of genes encoding fungal PKSs fell into eight groups. Four groups were
      predicted to synthesize variously reduced PKs, and four groups were predicted to
      make unreduced PKs. (iv). Species within different classes of Pezizomycotina
      shared the same groups of PKS genes. (v). Different fungal genomes shared few
      putative orthologous PKS genes, even between closely related genomes in the same
      class or genus. (vi) The discontinuous distributions of orthologous PKSs among
      fungal species can be explained by gene duplication, divergence, and gene loss;
      horizontal gene transfer among fungi does not need to be invoked.

PMID- 14676320
TI  - Electroosmotic enhancement of the binding of a neutral molecule to a
      transmembrane pore.
AB  - The flux of solvent water coupled to the transit of ions through protein pores is
      considerable. The effect of this electroosmotic solvent flow on the binding of a
      neutral molecule [beta-cyclodextrin (betaCD)] to sites within the staphylococcal
      alpha-hemolysin pore was investigated. Mutant alpha-hemolysin pores were used to
      which betaCD can bind from either entrance and through which the direction of
      water flow can be controlled by choosing the charge selectivity of the pore and
      the polarity of the applied potential. The Kd values for betaCD for individual
      mutant pores varied by >100-fold with the applied potential over a range of -120
      to +120 mV. In all cases, the signs of the changes in binding free energy and the
      influence of potential on the association and dissociation rate constants for
      betaCD were consistent with an electroosmotic effect.

PMID- 14676321
TI  - L-Lysine acts like a partial serotonin receptor 4 antagonist and inhibits
      serotonin-mediated intestinal pathologies and anxiety in rats.
AB  - The purpose of this investigation was to determine whether a nutritionally
      essential amino acid, l-lysine, acts like a serotonin receptor 4 (5-HT4)
      antagonist, and if l-lysine is beneficial in animal models of serotonin (5-HT)
      induced anxiety, diarrhea, ileum contractions, and tachycardia and in stress
      induced fecal excretion. The radioligand-binding assay was used to test the
      binding of l-lysine to various 5-HT receptors. The effects of l-lysine on 5-HT
      induced contractions of isolated guinea pig ileum were studied in vitro. The
      effects of oral administration of l-lysine on diarrhea, stress-induced fecal
      excretion, and 5-HT-induced corticosterone release, tachycardia, and anxiety (an
      elevated plus maze paradigm) were studied in rats in vivo. l-Lysine (0.8 mmol/dl)
      inhibited (9.17%) binding of 5-HT to the 5-HT4 receptor, without any effect on 5
      HT1A,2A,2B,2C,3 binding. l-Lysine (0.07 and 0.7 mmol/dl) blocked 5-HT-induced
      contractions of an isolated guinea pig ileum in vitro (P < 0.05 and P < 0.01).
      Orally applied l-lysine (1 g/kg of body weight) inhibited (P < 0.12) diarrhea
      triggered by coadministration of restraint stress and 5-hydroxytryptophane (10
      mg/kg of body weight), and significantly blocked anxiety induced by the 5-HT4
      receptor agonist (3.0 mmol/liter) in rats in vivo. No effects of l-lysine or the
      5-HT4 receptor agonist on plasma corticosterone and heart rate were recorded. l
      Lysine may be a partial 5-HT4 receptor antagonist and suppresses 5-HT4 receptor
      mediated intestinal pathologies and anxiety in rats. An increase in nutritional
      load of l-lysine might be a useful tool in treating stress-induced anxiety and 5
      HT-related diarrhea-type intestinal dysfunctions.

PMID- 14676322
TI  - High-resolution yeast phenomics resolves different physiological features in the
      saline response.
AB  - We present a methodology for gene functional prediction based on extraction of
      physiologically relevant growth variables from all viable haploid yeast knockout
      mutants. This quantitative phenomics approach, here applied to saline
      cultivation, identified marginal but functionally important phenotypes and
      allowed the precise determination of time to adapt to an environmental challenge,
      rate of growth, and efficiency of growth. We identified approximately 500 salt
      sensitive gene deletions, the majority of which were previously uncharacterized
      and displayed salt sensitivity for only one of the three physiological features.
      We also report a high correlation to protein-protein interaction data; in
      particular, several salt-sensitive subcellular networks indicating functional
      modules were revealed. In contrast, no correlation was found between gene
      dispensability and gene expression. It is proposed that high-resolution phenomics
      will be instrumental in systemwide descriptions of intragenomic functional
      networks.

PMID- 14676323
TI  - Redox-coupled proton translocation in biological systems: proton shuttling in
      cytochrome c oxidase.
AB  - In the respiratory chain free energy is conserved by linking the chemical
      reduction of dioxygen to the electrogenic translocation of protons across a
      membrane. Cytochrome c oxidase (CcO) is one of the sites where this linkage
      occurs. Although intensively studied, the molecular mechanism of proton pumping
      by this enzyme remains unknown. Here, we present data from an investigation of a
      mutant CcO from Rhodobacter sphaeroides [Asn-139 --> Asp, ND(I-139)] in which
      proton pumping is completely uncoupled from the catalytic turnover (i.e.,
      reduction of O2). However, in this mutant CcO, the rate by which O2 is reduced to
      H2O is even slightly higher than that of the wild-type CcO. The data indicate
      that the disabling of the proton pump is a result of a perturbation of E(I-286),
      which is located 20 A from N(I-139) and is an internal proton donor to the
      catalytic site, located in the membrane-spanning part of CcO. The mutation
      results in raising the effective pKa of E(I-286) by 1.6 pH units. An explanation
      of how the mutation uncouples catalytic turnover from proton pumping is offered,
      which suggests a mechanism by which CcO pumps protons.

PMID- 14676324
TI  - Loss of poly(ADP-ribose) glycohydrolase causes progressive neurodegeneration in
      Drosophila melanogaster.
AB  - Poly(ADP-ribosyl)ation has been suggested to be involved in regulation of DNA
      repair, transcription, centrosome duplication, and chromosome stability. However,
      the regulation of degradation of poly(ADP-ribose) and its significance are not
      well understood. Here we report a loss-of-function mutant Drosophila with regard
      to poly(ADP-ribose) glycohydrolase, a major hydrolyzing enzyme of poly(ADP
      ribose). The mutant lacks the conserved catalytic domain of poly(ADP-ribose)
      glycohydrolase, and exhibits lethality in the larval stages at the normal
      development temperature of 25 degrees C. However, one-fourth of the mutants
      progress to the adult stage at 29 degrees C but showed progressive
      neurodegeneration with reduced locomotor activity and a short lifespan. In
      association with this, extensive accumulation of poly(ADP-ribose) could be
      detected in the central nervous system. These results suggest that poly(ADP
      ribose) metabolism is required for maintenance of the normal function of neuronal
      cells. The phenotypes observed in the parg mutant might be useful to understand
      neurodegenerative conditions such as the Alzheimer's and Parkinson's diseases
      that are caused by abnormal accumulation of substances in nervous tissue.

PMID- 14676325
TI  - A tenascin-C aptamer identified by tumor cell SELEX: systematic evolution of
      ligands by exponential enrichment.
AB  - The targeting of molecular repertoires to complex systems rather than
      biochemically pure entities is an accessible approach that can identify proteins
      of biological interest. We have probed antigens presented by a monolayer of tumor
      cells for their ability to interact with a pool of aptamers. A glioblastoma
      derived cell line, U251, was used as the target for systematic evolution of
      ligands by exponential enrichment by using a single-stranded DNA library. We
      isolated specifically interacting oligonucleotides, and biochemical strategies
      were used to identify the protein target for one of the aptamers. Here we
      characterize the interaction of the DNA aptamer, GBI-10, with tenascin-C, an
      extracellular protein found in the tumor matrix. Tenascin-C is believed to be
      involved in both embryogenesis and oncogenesis pathways. Systematic evolution of
      ligands by exponential enrichment appears to be a successful strategy for the a
      priori identification of targets of biological interest within complex systems.

PMID- 14676326
TI  - Antitumor efficacy of cytotoxic drugs and the monoclonal antibody 806 is enhanced
      by the EGF receptor inhibitor AG1478.
AB  - Blockade of epidermal growth factor receptor (EGFR) signaling with specific
      inhibitors of the EGFR tyrosine kinase retards cellular proliferation and arrests
      the growth of tumor xenografts. AG1478, an inhibitor of the EGFR tyrosine kinase,
      is used in laboratory studies; however, its therapeutic potential has not been
      elucidated. Therefore, we evaluated an aqueous form of AG1478 for its antitumor
      activity in mice bearing human xenografts expressing the WT EGFR or a naturally
      occurring ligand-independent truncation of the EGFR [delta2-7 (de2-7) EGFR or
      EGFRvIII]. Parenteral administration of soluble AG1478 blocked phosphorylation of
      the EGFR at the tumor site and inhibited the growth of A431 xenografts that
      overexpress the WT EGFR and glioma xenografts expressing the de2-7 EGFR.
      Strikingly, even subtherapeutic doses of AG1478 significantly enhanced the
      efficacy of cytotoxic drugs, with the combination of AG1478 and temozolomide
      displaying synergistic antitumor activity against human glioma xenografts. AG1478
      was also examined in combination with mAb 806, an anti-EGFR antibody that was
      raised against the de2-7 EGFR but unexpectedly also binds a subset of the EGFR
      expressed in cells exhibiting amplification of the EGFR gene. The combination of
      AG1478 and mAb 806 displayed additive, and in some cases synergistic, antitumor
      activity against tumor xenografts overexpressing the EGFR. Here, we demonstrate
      that different classes of inhibitors to the EGFR can have synergistic antitumor
      activity in vivo. These results establish the antitumor efficacy of the EGFR
      inhibitor AG1478 and provide a rationale for its clinical evaluation in
      combination with both chemotherapy and other EGFR therapeutics.

PMID- 14676327
TI  - Seeking new meiotic genes.

PMID- 14676328
TI  - Another twist in the transforming growth factor beta-induced cell-cycle arrest
      chronicle.

PMID- 14676329
TI  - Costimulatory signals controlling regulatory T cells.

PMID- 14676330
TI  - Activation of peroxisome proliferator-activated receptor delta induces fatty acid
      beta-oxidation in skeletal muscle and attenuates metabolic syndrome.
AB  - In this study, we defined the role of peroxisome proliferator-activated receptor
      beta/delta (PPARdelta) in metabolic homeostasis by using subtype selective
      agonists. Analysis of rat L6 myotubes treated with the PPARdelta subtype
      selective agonist, GW501516, by the Affymetrix oligonucleotide microarrays
      revealed that PPARdelta controls fatty acid oxidation by regulating genes
      involved in fatty acid transport, beta-oxidation, and mitochondrial respiration.
      Similar PPARdelta-mediated gene activation was observed in the skeletal muscle of
      GW501516-treated mice. Accordingly, GW501516 treatment induced fatty acid beta
      oxidation in L6 myotubes as well as in mouse skeletal muscles. Administration of
      GW501516 to mice fed a high-fat diet ameliorated diet-induced obesity and insulin
      resistance, an effect accompanied by enhanced metabolic rate and fatty acid beta
      oxidation, proliferation of mitochondria, and a marked reduction of lipid
      droplets in skeletal muscles. Despite a modest body weight change relative to
      vehicle-treated mice, GW501516 treatment also markedly improved diabetes as
      revealed by the decrease in plasma glucose and blood insulin levels in
      genetically obese ob/ob mice. These data suggest that PPARdelta is pivotal to
      control the program for fatty acid oxidation in the skeletal muscle, thereby
      ameliorating obesity and insulin resistance through its activation in obese
      animals.

PMID- 14676331
TI  - Proteomic analysis of oxidative stress-resistant cells: a specific role for
      aldose reductase overexpression in cytoprotection.
AB  - We are using a proteomic approach that combines two-dimensional electrophoresis
      and tandem mass spectrometry to detect and identify proteins that are
      differentially expressed in a cell line that is resistant to oxidative stress.
      The resistant cell line (OC14 cells) was developed previously through chronic
      exposure of a parent cell line (HA1 cells) to increasing hydrogen peroxide
      concentrations. Biochemical analyses of this system by other investigators have
      identified elevated content and activity of several classical antioxidant
      proteins that have established roles in oxidative stress resistance, but do not
      provide a complete explanation of this resistance. The proteomics studies
      described here have identified the enzyme aldose reductase (AR) as 4-fold more
      abundant in the resistant OC14 cells than in the HA1 controls. Based on this
      observation, the role of AR in the resistant phenotype was investigated by using
      a combination of AR induction with ethoxyquin and AR inhibition with Alrestatin
      to test the cytotoxicity of two oxidation-derived aldehydes: acrolein and
      glycolaldehyde. The results show that AR induction in HA1 cells provides
      protection against both acrolein- and glycolaldehyde-induced cytotoxicity.
      Furthermore, glutathione depletion sensitizes the cells to the acrolein-induced
      toxicity, but not the glycolaldehyde-induced toxicity, while AR inhibition
      sensitizes the cells to both acrolein- and glycolaldehyde-induced. These
      observations are consistent with a significant role for AR in the oxidative
      stress-resistant phenotype. These studies also illustrate the productive use of
      proteomic methods to investigate the molecular mechanisms of oxidative stress.

PMID- 14676333
TI  - American football and the evolution of modern sports medicine.

PMID- 14676334
TI  - Prognostic indicators for outcome following rotator cuff tear repair.
AB  - PURPOSE: To examine the prognostic indicators associated with outcome following
      rotator cuff surgery. METHODS: A retrospective evaluation of records on 1120
      shoulders (1067 patients) with rotator cuff tear treated by surgery was
      performed. Preoperative, intra-operative and postoperative factors were analysed
      by Kendall's Tau-b correlation analysis and logistic regression analysis.
      RESULTS: Positive correlations were seen between the type of tear and the number
      of tendons involved, retraction, age, degeneration, subacromial bone spur,
      surgical technique, preoperative and postoperative muscle power, surgical
      outcome, and preoperative abduction on Kendall's Tau-b analysis. There was a
      positive correlation seen between degenerative change and age, number of tendons
      involved, retraction, preoperative pain, tear type, and preoperative musclepower
      on logistic regression analysis. Additionally, positive correlations were seen
      between good surgical postoperative outcome and postoperative activities of daily
      living, preoperative pain, postoperative muscle power, preoperative activities of
      daily living, tear type, preoperative external rotation, preoperative muscle
      power, number of tendons involved, preoperative pain, and duration of symptoms.
      CONCLUSION: Ageing was found to be the major factor in progressive degeneration
      of the rotator cuff, and should be considered the single most important
      contributing factor in the pathogenesis of rotator cuff tears. In addition,
      degenerative tendonopathy appeared the primary pathology in rotator cuff tear,
      preceding hypertrophic spur formation. Rotator cuff tears are therefore unlikely
      to be initiated by impingement; rather, they develop as an intrinsic degenerative
      tendonopathy.

PMID- 14676335
TI  - Autogenous osteochondral grafts for osteonecrosis of the femoral condyle.
AB  - PURPOSE: To evaluate the long-term outcome following use of osteochondral
      autografts for the treatment of osteonecrosis of the femoral condyle. METHODS:
      Clinical, radiographic and arthroscopic findings were evaluated at follow-up.
      Patients were 14 women and 2 men, with a mean age of 64.9 years (range, 58-74
      years). The osteochondral lesion was equivalent to Lotke 1-B in 12 knees, and was
      equivalent to 1-C in 4 knees. Preoperative femoral tibia angle ranged from 178
      degrees to 190 degrees. RESULTS: The follow-up period ranged from 28 months to
      111 months (mean, 67 months). Functional scores improved from 60 to 75
      preoperatively to 80 to 100 postoperatively, and the grafts were satisfactorily
      accepted. Patients with a femoral tibia angle of less than 180 degrees in
      particular were found to respond favourably. CONCLUSION: Transplant surgery using
      osteochondral autografting appeared effective for the treatment of osteonecrosis
      of femoral condyle.

PMID- 14676336
TI  - Minimally displaced intra-capsular femoral neck fractures in the elderly-
      comparison of multiple threaded pins and sliding compression screws surgical
      techniques.
AB  - PURPOSE: To determine the outcome of treatment for minimally displaced femoral
      neck fractures using multiple threaded pins versus sliding compression screws for
      internal fixation. METHODS: The medical records of 62 consecutive elderly
      patients with minimally displaced intra-capsular femoral neck fractures who
      underwent internal fixation of the fracture (37 with multiple threaded pins, and
      25 with sliding compression screws) were reviewed. Clinical and radiological
      assessment of fracture healing at follow-up visits were noted. RESULTS: In the 55
      patients seen for follow-up at 3 months, 21.9% (n=7) of those treated by pinning
      demonstrated non-union of the fracture, and 0% of fractures treated with sliding
      compression screws (p=0.02). 46 patients were seen for follow-up at one year,
      with 10% (n=2) of those treated with sliding compression screws found to have
      osteonecrosis of the femoral head. The 2 fractures in the group treated by
      pinning demonstrating non-union at 3 months failed to unite by one year (p=0.11).
      34 patients were seen for follow-up for at least 2 years, with no additional
      complications noted. CONCLUSION: Using sliding compression screws to treat
      minimally displaced femoral neck fractures can achieve a higher union rate than
      using pinning. The reason may be the better stability in the osteoporotic bone.
      However, osteonecrosis of the femoral head may occur with use of sliding
      compression screws because of greater intramedullary vascular damage as a result
      of wider reaming.

PMID- 14676337
TI  - Quantitative anatomic characterisation of the pelvic brim to facilitate internal
      fixation through an anterior approach.
AB  - PURPOSE: To define the centre of the hip joint and the bone stock around the hip
      joint from the supra-acetabular portion or pelvic brim so as to avoid penetration
      of guidewire into the hip joint when performing internal fixation using the
      anterior approach. METHODS: A total of 42 cadavers were utilised. Measurements
      were completed before and after cutting the pelvis into 4 pieces. Before cutting
      the pelvis, the centre of the hip joint was measured on the pelvic brim. After
      cutting the pelvis, the bone stock around the hip joint was measured in each
      section. The pelvic brim and the anteroinferior iliac spine were utilised as
      guide points in the measurements, because these parameters could be determined
      during an anterior surgical procedure. RESULTS: On the pelvic brim, the reflected
      centre of the hip joint centre was located approximately 3.2 mm anterior to the
      distal edge of the anteroinferior iliac spine. The mean minimum bone stock of the
      pelvic brim was 14.0 mm in the centre of the hip joint section. CONCLUSION: This
      study described the anatomical reference points around the hip joint, and the
      ways in which they can be utilised to increase the safety of the anterior
      approach for internal fixation. It is important to define the centre of the hip
      joint from the supra-acetabular portion or pelvic brim, given that it is not
      visualised during surgery using an anterior approach.

PMID- 14676338
TI  - Supracondylar nailing for difficult distal femur fractures.
AB  - PURPOSE: To evaluate outcome following supracondylar nailing for distal femur
      fractures. METHODS: The clinical and radiological outcome for 13 patients treated
      between January 1995 and December 1998 at the University Malaya Medical Center
      was assessed. Patients were seen for follow-up for a mean duration of 20.2
      months. RESULTS: There were no cases of non-union or infection. Overall
      assessment of clinical outcome based on the criteria of Schatzker and Lambert was
      graded excellent in 6 patients, good in 3 patients, fair in 3 patients, and one
      graded as a failure. CONCLUSION: Supracondylar nailing for fixation of
      supracondylar (Arbeitsgemeinschaft fur Osteosynthesefragen [AO] type A) and less
      comminuted intercondylar (AO type C1 and C2) fractures is recommended by the
      authors.

PMID- 14676339
TI  - Small stem Exeter total hip replacement: clinical and radiological follow-up over
      a minimum of 2.5 years.
AB  - PURPOSE: To evaluate the clinical and radiological outcome in patients undergoing
      small stem Exeter total hip replacement. METHODS: A total of 46 small stem Exeter
      total hip replacements were performed on 44 consecutive patients (18 men and 26
      women) attending the University of Malaya Medical Centre. The mean age at the
      time of operation was 58 years (range, 24-81 years). Of the 46 procedures
      performed, 35 were primary total hip replacements and 11 were revision
      operations, with aseptic loosening of the original implant being the main
      indication for revision. The main indications for surgery in primary cases were
      avascular necrosis and rheumatoid arthritis. Clinical and radiographic outcomes
      were assessed at 6 weeks', 12 weeks', 6 months' follow-up, and annually
      thereafter. Postoperative cementing technique was also assessed. RESULTS: The
      mean follow-up period was 4 years. The mean Oxford Hip Score improved from 46
      points preoperatively to 17 points at the final follow-up examination. There were
      no revision operations, no implant breakages, and no excessive migration of the
      implants. The potential complications of implant failure due to smaller implant
      size and increased patient activity were not observed. CONCLUSION: Due to the
      smaller size of Asian femora, the small stem Exeter implant is a very useful
      development. This study suggests that it will perform as well as its larger
      counterparts.

PMID- 14676340
TI  - Gait adaptations in patients with longstanding hip fusion.
AB  - PURPOSE: To examine the long-term effects of hip arthrodesis in terms of gait
      adaptations. METHODS: Motion analysis was performed on 9 patients who underwent
      unilateral hip arthrodesis between 1979 and 1991. A standard clinical gait
      analysis 3-dimensional model for the lower limb was used to calculate the effect
      of the fused hip on walking, compared with the contralateral normal hip. RESULTS:
      Significant (p<0.05) gait adaptations noted in the fused side were, compensatory
      hip hiking during the swing-phase, a 24% reduction in hip adduction moment, a 37%
      decrease in genu-varus moment, 80% reduced hip power, and excessive pelvic tilt.
      CONCLUSION: It appears that the excess pelvic tilt observed was to achieve
      relative hip extension via increased relative lumbar lordosis, while the
      decreased coronal plane moments of the hip and knee observed were to reduce joint
      loading on the affected side.

PMID- 14676341
TI  - Medium-term results of cementless hydroxyapatite-coated primary total hip
      arthroplasty: a clinical and radiological review.
AB  - PURPOSE: To evaluate the clinical and radiological outcomes following cementless
      primary hydroxyapatite-coated total hip arthroplasty. METHODS: A retrospective
      study of 69 patients (82 hips) who underwent uncemented hydroxyapatite-coated
      Anatomic Benoist Girard total hip replacement between October 1991 and October
      1995 at our institution was conducted. Patient records were reviewed. All
      patients were evaluated clinically using the Merle D'Aubigne hip score, and
      osteointegration was assessed radiographically by analysing the bone implant
      interface in the 7 zones of Gruen on followup review. RESULTS: The mean follow-up
      period was 7.3 years. Clinical results were excellent with an improvement seen in
      clinical score from 9.9 preoperatively to 16.5 at last review. A total of 15% of
      patients recorded some thigh discomfort, which was intermittent and not
      functionally limiting, except in 2 cases. There were 3 cases of severe acetabular
      osteolysis and loosening requiring revision surgery, and 4 cases of localised
      proximal femoral osteolysis around well-ingrown implants. There were few
      perioperative complications, with the exception of 5 dislocations of which 3 were
      recurrent and required a revision procedure. CONCLUSION: Clinical and
      radiological outcomes following cementless hydroxyapatite-coated total hip
      arthroplasty were seen to be favourable in this medium-term retrospective study.

PMID- 14676342
TI  - Clinical pathways in total knee arthroplasty: a New Zealand experience.
AB  - PURPOSE: To ascertain the effects of a clinical pathway in our institution.
      METHODS: This retrospective and comparative study was performed on all patients
      undergoing total knee arthroplasty over a 5-year period. This period covered the
      30 months prior to the introduction of the pathway (group 1), and the 30 months
      following its introduction (group 2). RESULTS: There was a significant reduction
      in the duration of hospital stay of group 2 patients (p<0.0001), with 62.8% of
      these patients staying less than 8 postoperative days. There was a reduction in
      the number of patients with thromboembolic complications (p<0.05) and no increase
      in overall complications or readmission rate. There was a trend to increased use
      of rehabilitation services among group 2 patients. CONCLUSION: Clinical pathway
      implementation resulted in a significant reduction in the length of stay, and
      achieved a more efficient management of hospitalised patients without
      compromising outcome.

PMID- 14676343
TI  - The incidence of deep vein thrombosis after hip and knee arthroplasties in
      Japanese patients: a prospective study.
AB  - PURPOSE: To document the incidence of proximal deep vein thrombosis and pulmonary
      embolism in 58 consecutive Japanese patients undergoing total hip arthroplasty or
      total knee arthroplasty. METHODS: Patients were routinely examined for proximal
      deep vein thrombosis by B-mode ultrasonography before and after surgery. Those
      patients who had ultrasonographic findings of deep vein thrombosis were also
      investigated for pulmonary embolism by ventilation-perfusion lung scan. RESULTS:
      The incidence of deep vein thrombosis after total hip arthroplasty and total knee
      arthroplasty were 9.1% and 4.0% respectively, and the incidence of pulmonary
      embolism were 3.0% and 0%, respectively. There were no cases of fatal pulmonary
      embolism. CONCLUSION: The incidence of deep vein thrombosis and pulmonary
      embolism in Japanese patients may have increased over the last few decades.

PMID- 14676344
TI  - Malaysian orthopaedic surgeons' approach to venous thromboembolic disease
      prophylaxis: attitudes and practice.
AB  - PURPOSE: To survey Malaysian orthopaedic surgeons' attitudes to and use of venous
      thromboembolic disease prophylaxis. METHODS: A total of 144 orthopaedic surgeons
      from various governmental and private institutions responded to a questionnaire.
      RESULTS: Only slightly more than half of these surgeons considered venous
      thromboembolic disease as common a problem in Malaysia as in western countries.
      The majority of surgeons (91.0%) reported using prophylaxis selectively for
      patients based on various indicators such as risk grading of surgery, obesity,
      and malignancy etc. Bleeding tendencies were cited as the greatest fear against
      the use of pharmacological prophylaxis. Low-molecular-weight heparin appeared to
      be the most commonly used pharmacological prophylaxis, used either singly or in
      combination with other forms of prophylaxis. The majority of surgeons employed
      prophylaxis until their patients were mobile. CONCLUSION: There should be greater
      awareness among surgeons in Malaysia of the need for protection against venous
      thromboembolic disease. Current practice needs to be reviewed and further
      recommendations made for existing protocols.

PMID- 14676345
TI  - The incidence of proximal deep vein thrombosis following total knee arthroplasty
      in an Asian population: a Doppler ultrasound study.
AB  - PURPOSE: To investigate the incidence of deep vein thrombosis (DVT) following
      total knee arthroplasty in an Asian population. METHODS: A prospective study of
      149 consecutive cases of total knee arthroplasty done for osteoarthritis was
      conducted over a 5-year period. All patients underwent duplex ultrasonographic
      assessment of the lower limbs within the first postoperative week. RESULTS: The
      incidence of proximal DVT was found to be 4.38% in this study. Symptomology was
      statistically significant in predicting the presence of proximal DVT in all
      cases. General anaesthesia was associated with a statistically significant-higher
      incidence of DVT as compared with regional anaesthesia. There was a significant
      association between a sedentary lifestyle and the development of DVT. CONCLUSION:
      The incidence of proximal DVT in Asian patients after total knee arthroplasty is
      higher than that previously reported for this demographic group.

PMID- 14676346
TI  - The relationship between nerve conduction study and clinical grading of carpal
      tunnel syndrome.
AB  - PURPOSE: To conduct a median nerve conduction study on patients with carpal
      tunnel syndrome and investigate the relationship between nerve conduction study
      parameters and clinical grading. METHODS: A nerve conduction study was performed
      on 60 upper limbs of 37 patients with idiopathic carpal tunnel syndrome, and the
      relationship between the clinical grade and various study parameters was
      assessed. RESULTS: The amplitude of the sensory nerve action potential and the
      motor nerve action potential differed according to clinical grading, but this
      pattern was not seen for sensory nerve conduction velocity, motor nerve
      conduction velocity, or motor nerve terminal latency and clinical grading.
      CONCLUSION: The amplitude of the sensory nerve action potential and motor nerve
      action potential reflect the functional state of axons, and are useful parameters
      for assessing clinical grading based on nerve conduction velocity.

PMID- 14676347
TI  - Role of Joshi's external stabilisation system fixator in the management of
      idiopathic clubfoot.
AB  - PURPOSE: To explore the role of Joshi's external stabilisation system fixator in
      correcting cases of clubfoot peculiar to India, we studied cases of neglected
      clubfoot, dropout cases of plaster-of-paris cast treatment, or failed surgical
      procedures that had been followed for a minimum period of 2 years. METHODS: 26
      children underwent 44 Joshi's external stabilisation system procedures at the
      Central Institute of Orthopaedics at the Safdarjung Hospital, New Delhi, between
      January 1998 and December 1999 for the conditions of interest. Three-dimensional
      correction was achieved by use of the distractor device. RESULTS: Excellent
      results were obtained in 77% of the cases, good results in 13%, and poor results
      in 9% of the cases. Complications in half of the cases were pintract infections,
      which eventually healed on an outpatient basis without any residual sequelae.
      CONCLUSION: The Joshi's external stabilisation system frame is ideally suited for
      the child in whom clubfoot deformities remain uncorrected by plaster-of-paris
      casts and manipulation, as well as for recurrent clubfoot. Casting after complete
      correction not only protects the osteopenic bones while the pin-tracts heal, but
      also maintains correction and allows gradual weightbearing.

PMID- 14676348
TI  - Degenerative spondylolisthesis at the L4-L5 in a 32-year-old female with previous
      fusion for idiopathic scoliosis: a case report.
AB  - We report a case of degenerative L4-L5 spondylolisthesis in a 32-year-old female
      who had undergone thoracic (lower level T12) fusion as a teenager. All other
      levels in the lumbar spine were normal on magnetic resonance imaging. Subsequent
      fusion of L4-L5 led to improvement in function and alleviation of pain for more
      than 4 years. The possible relationship between the previous fusion and
      degenerative spondylolisthesis is discussed.

PMID- 14676349
TI  - Bilateral capitellum humeri fracture: a case report and review of the literature.
AB  - We report a case of a 37-year-old woman who sustained a bilateral Hahn-Steinthal
      type fracture of her capitellum humeri. Open reduction and internal fixation,
      using extra-articular insertion of Herbert screws, were performed. Both elbows
      were immobilised for 3 weeks postoperatively. Radiographic signs of union were
      present at week 8. Within the observation period of 18 months, no signs of
      avascular necrosis were detected. At the end of the recovery period, despite
      intensive physiotherapy, the patient was left with a 20 degrees loss of flexion
      in her right elbow and a 15 degrees loss of extension in her left elbow. We found
      the use of Herbert screws particularly suitable for this type of injury: it
      allows good inter-fragmentary compression due to the sub-articular positioning
      that avoids the risk of damaging the articular surface. Mobilisation should start
      early to prevent joint stiffness and long-term disability.

PMID- 14676350
TI  - Lunate migration following Darrach's procedure: a case report.
AB  - We report a case of a 28-year-old female patient who underwent Darrach's
      procedure to her dominant right wrist affected by rheumatoid disease. She
      developed severe pain in the wrist 4 weeks postoperatively. Collapse of the
      scaphoid and proximal migration of the lunate was noted. Total wrist arthrodesis
      using the Arbeitsgemeinschaft fur Osteosynthesefragen wrist arthrodesis plate was
      performed, which alleviated the pain. Darrach's procedure is described for
      conditions causing derangement of the distal radio-ulnar joint, the classical
      inflammatory cause being rheumatoid arthritis. It is however a potentially
      destabilising procedure. The extreme complication encountered in this case
      highlights the risk of Darrach's procedure if pre-existing ligamentous
      instability is present.

PMID- 14676351
TI  - Salmonella osteomyelitis in an otherwise healthy adult male-successful management
      with conservative treatment: a case report.
AB  - A 21-year-old male presented with pain in the right thigh of insidious onset and
      3 months' duration. He had a history of febrile illness lasting for 15 days, 2
      months prior to the onset of pain. Examination revealed swelling over the lower
      lateral aspect of the right thigh with some induration and tenderness. Initial X
      rays of the right femur and the computed tomography scan at 10 weeks after the
      onset of disease were normal. Magnetic resonance imaging scan showed signal
      alteration with minimal destruction of the anterior cortex in the mid-diaphyseal
      region of the right femur. A repeated X-ray taken at 15 weeks after the onset of
      illness showed erosive changes, along with periosteal reaction in the diaphyseal
      area. The Widal test was positive. Open biopsy of the lesion revealed
      inflammatory non-caseating tissue. Culture of the specimen grew Salmonella typhi.
      The patient was given antibiotic treatment. Both X-rays and the Widal titres were
      normal on subsequent follow-up at 3 months.

PMID- 14676352
TI  - Group G streptococcus--a rare cause of osteomyelitis simulating bone tumour: a
      case report.
AB  - We report a case of osteomyelitis of the proximal femur caused by Lancefield
      group G streptococcus in a 71-year-old otherwise healthy man. The organism has
      rarely been identified as the cause of osteomyelitis. The subacute nature of the
      symptoms and the radiological appearance of the femur in this patient mimic bone
      tumour. The patient was successfully treated with conservative methods, including
      a prolonged period of oral antibiotics. We stress the importance of histological
      and bacteriological evidence in avoiding misdiagnosing patients with equivocal
      clinical and radiological presentation.

PMID- 14676353
TI  - A report of two cases of Werner's syndrome and review of the literature.
AB  - Two cases of Werner's syndrome are reported. The first case is that of a man with
      grey hair since his 20s, and alopecia since aged about 50 years. At the age of 53
      years, Werner's syndrome was diagnosed, along with a malignant soft tissue tumour
      of the hand. The patient underwent ray amputation for the tumour. The subsequent
      histopathological diagnosis was synovial cell sarcoma, and the patient died of
      lung metastasis at 15 weeks postsurgery. The second case is that of a woman
      diagnosed with diabetes mellitus when aged 34 years. At 39 years, a bilateral
      cataract was diagnosed and at 40 years, diabetic gangrene of the left calcaneal
      region and calcaneal osteomyelitis necessitated left below-knee amputation. The
      incidence of Werner's syndrome in Japan is extremely high (1000 of the around
      1300 cases reported worldwide) compared to other countries. Most patients develop
      malignant tumour or arteriosclerosis, the most important complications of this
      syndrome. The average life expectancy for patients with Werner's syndrome is 46
      years. The incidence of epithelial cancer and mesenchymal sarcoma is 10 times
      that of the general population. The onset of symptoms of Werner's syndrome
      generally precedes any later symptoms of associated conditions, such as malignant
      tumour. Therefore, early recognition of Werner's syndrome is important to assist
      identification of malignant tumours at an early stage in this patient group.

PMID- 14676354
TI  - Medial meniscal cyst of the knee--an unusual presentation: a case report.
AB  - We report an unusual case of a large, asymptomatic, medial meniscal cyst of the
      knee. Medial meniscal cysts are relatively uncommon, are usually symptomatic and
      in most cases are so small that only magnetic resonance imaging can confirm the
      diagnosis.

PMID- 14676355
TI  - The effect of clinorotation on vestibular compensation in upside-down swimming
      catfish.
AB  - Upside-down swimming catfish Synodontis nigriventris can keep upside-down
      swimming posture stably under pseudo-microgravity generated by clinostat. When
      the vestibular organ is unilaterally ablated, the operated S. nigriventris shows
      disturbed swimming postures under the clinorotation condition. However, about 1
      month after the operation, unilateral vestibular organ-ablated S. nigriventris
      shows stable upside-down swimming posture under the condition (vestibular
      compensation). In contrast, a closely related upside-up swimming catfish
      Synodontis multipunctatus belonging to same Synodontis family can not keep stable
      swimming postures under the clinorotation conditions. In this study, we examined
      the effect of continuous clinorotation on vestibular compensation in intact and
      unilateral vestibular organ-ablated Synodontis nigriventris and Synodontis
      multipunctatus. After the exposure to continuous clinorotation, the postures of
      the catfish were observed under microgravity provided by parabolic flights of an
      aircraft. Unilateral vestibular organ-ablated S. nigriventris which had been
      exposed to continuous clinorotation showed stable swimming postures and did not
      show dorsal light reaction (DLR) under microgravity. This postural control
      pattern of the operated catfish was similar to that of intact catfish. Intact and
      unilateral vestibular organ-ablated S. multipunctatus showed DLR during
      microgravity. Our results confirmed that S. nigriventris has a novel balance
      sensation which is not affected by microgravity. DLR seems not to play an
      important role in postural control. It remains unclear that the continuous
      clinorotation effects on vestibular compensation because we could not keep used
      unilateral vestibular organ-ablated fish alive under continuous clinorotation for
      uninterrupted 25 days. This study suggests that space flight experiments are
      required to explore whether gravity information is essential for vestibular
      compensation.

PMID- 14676356
TI  - Two types of response property in otolith-optokinetic interaction.
AB  - Otolithic influence on optokinetic eye-movements (visual-vestibular interaction)
      was investigated using oscillation of a lateral linear acceleration-step combined
      with optokinetic stimulation. According to our preliminary study using a 40-deg/s
      optokinetic stimulus speed at 0.3 and 0.5 G acceleration-steps, the interaction
      was characterized by a linear addition during the agonistic stimulus condition,
      but by suppression of the otolith-ocular reflex during the antagonistic stimulus
      condition. In the present study, we further examined the interaction using 3
      different optokinetic speeds at an acceleration step of 0.3 G. It was revealed an
      additional type of response property that was characterized by marked elevation
      in the eye velocity with increase in the optokinetic stimulus speed, probably due
      to the gain increase in the optokinetic response velocity. In either type of the
      response property, however, the interaction seemed to be nonlinear in the otolith
      system, being in contrast to linear interaction postulated for the semicircular
      canal system.

PMID- 14676357
TI  - Function of otolith organ in goldfish revealed from analysis of eye movement
      induced by acceleration.
AB  - An otolith organ on ground behave as a detector of both gravity and linear
      acceleration, and play an important role in controlling posture and eye movement
      for tilt of the head or translational motion. On the other hand, a gravitational
      acceleration ingredient to an otolith organ disappears in microgravity
      environment. However, linear acceleration can be received by otolith organ and
      produce a sensation that is different from that on Earth. It is suggested that in
      microgravity signal from the otolith organ may cause abnormality of posture
      control and eye movement. Therefore, the central nervous system may re-interprets
      all output from the otolith organ to indicate linear motion. A study of eye
      movement has been done a lot as one of a reflection related to an otolith organ
      system. In this study, we examined function of otolith organ in goldfish revealed
      from analysis of eye movement induced by linear acceleration or the tilt of body.
      We analyzed both torsional and vertical eye movements from video images frame by
      frame. For tilting stimulation, torsional eye movements induced by head down was
      larger than that induced by head up for larger tilt angle than 30 degrees. In the
      case of linear acceleration below 0.4 G, however, no clear differences were
      observed in both torsional and vertical eye movement. These results suggest that
      body tilt and linear acceleration may not be with equivalent stimulation to cause
      eye movement on the ground.

PMID- 14676358
TI  - Characterization of a gene respondent to clinorotation in Xenopus A6 cells.
AB  - The A6 epithelial cell line, derived from the kidney of Xenopus laevis,
      spontaneously form domes after it has reached confluence. In a previous study, we
      demonstrated that formation of domes is strongly inhibited in the cells cultured
      using a three-dimensional clinostat. In this study, we performed staining of
      filamentous actin and examination using electron microscopy to investigate
      morphological changes of A6 cells exposured to clinorotation for 10 days.
      Micrographs show that A6 cells in clinorotation lose cortical actin that is
      characteristic of epithelial cells. Therefore, we search for genes differentially
      expressed in A6 cells cultured in clinorotation and identified Xenopus laevis N
      myc downstream-regulated gene-1 (xNDRG1) as a clinorotation respondent gene in A6
      cells. In northern blots analysis, xNDRG1 mRNA significantly increased only in A6
      cells cultured in clinorotation for 10 days, and maintained at a similar level in
      the cells cultured for 15 days. Centrifugations of A6 cells have no effect on
      expression of xNDRG1. We also aimed to characterize xNDRG1 during Xenopus laevis
      development by examining the temporal and spatial expression patterns of xNDRG1
      transcripts in embryos. Our results suggest that xNDRG1 is necessary for
      pronephros development in Xenopus laevis.

PMID- 14676359
TI  - Morphological characteristics of the kidney and lung in the neonatal rats
      observed after 16 days spaceflight.
AB  - The aim of this study is to examine the structural development in kidney and lung
      macroscopically which relate with cardiovascular system in rats raised in space.
      Twenty three nine-day old rats and six fifteen-day old rats, which were launched
      at these ages and nursed by their dams in the Space Shuttle Colombia for 16 days
      (STS-90; Neurolab). Seventeen animals of the nine-day old rats were defined as
      the nine-day group, and the rest was defined as the re-adaptation group, which
      were reared on the ground for 30 more days after landing. The organs were weighed
      and the ratio of the organ weight to the body weight (body weight ratio) was
      calculated. Both of lung and kidney in flight rats were significantly heavier
      than ground controls in the body weight ratio. We found that the kidney in the
      nine-day and the fifteen-day group tended to extend of dorsal-ventral length in
      macroscopic observations. However, this difference was not observed in the re
      adaptation group. These results suggest that space environment may affect in
      kidney development. On the other hand, the lung had no differences in macroscopic
      structure among flight and control groups.

PMID- 14676360
TI  - Expression of PIN and AUX1 genes encoding putative carrier proteins for auxin
      polar transport in etiolated pea epicotyls [correction of epicotyles] under
      simulated microgravity conditions on a three-dimensional clinostat.
AB  - Etiolated pea (Pisum sativum L. cv. Alaska) seedlings grown under simulated
      microgravity conditions on a 3-dimensional clinostat showed automorphosis-like
      growth and development similar to that observed in true microgravity conditions
      in space. Application of inhibitors of auxin polar transport phenocopied
      automorphosis-like growth on 1 g conditions, suggesting that automorophosis is
      closely related to auxin polar transport. Strenuous efforts to know the
      relationships between automorphosis and auxin polar transport in pea seedlings at
      molecular bases resulted in successful identification of PsPIN2 and PsAUX1
      encoding putative auxin efflux and influx carrier protein, respectively.
      Significantly high levels in homology were found on nucleotide and deduced amino
      acid sequences among PsPIN2, PsPIN1 and AtPINs, and between PsAUX1 and AtAUX1.
      Expression of PsPIN1 and PsAUX1 genes in etiolated pea seedlings grown on the
      clinostat were substantially affected, but that of PsPIN2 was not. Roles of these
      genes in auxin polar transport and automorphosis of etiolated pea seedlings are
      also described.

PMID- 14676361
TI  - Increase in expression level of alpha-tubulin gene in Arabidopsis seedlings under
      hypergravity conditions.
AB  - Under hypergravity conditions, elongation growth of plant shoots is suppressed.
      The analysis of the changes in gene expression by hypergravity treatment in
      Arabidopsis hypocotyls by the differential display method showed that a gene
      encoding alpha-tubulin, which is a component of microtubules, was up-regulated by
      hypergravity. In Arabidopsis six genes encoding alpha-tubulin (TUA1-TUA6) have
      been identified. In the present study, we examined the dose-response and the time
      course relations of the changes in the expression of all six alpha-tubulin genes
      in Arabidopsis hypocotyls grown under hypergravity conditions. The expression
      levels of all six alpha-tubulin genes, TUA1-TUA6, were increased by increasing
      gravity, although the extent was variable among genes. The increase in expression
      of all alpha-tubulin genes was detected within a few hours, when the seedlings
      grown at 1 g were transferred to 300 g condition. These results suggest that
      Arabidopsis hypocotyls regulate the expression level of six alpha-tubulin genes
      promptly in response to gravity stimuli. The increase in the amount of
      microtubules due to the activation of tubulin gene expression may be involved in
      the regulation by gravity signal of shoot growth.

PMID- 14676362
TI  - Perception mechanism of gravity stimuli in hypergravity-induced growth inhibition
      of azuki bean roots.
AB  - We reported that elongation growth of plant shoots and roots is suppressed by
      hypergravity, with the rate decreasing in proportion to logarithm of the
      magnitude of gravity. In hypergravity-induced growth inhibition of shoots,
      graviperception is supposed to be independent of that in gravitropism and to
      involve mechanoreceptors. However, the graviperception mechanism in the
      hypergravity-induced growth inhibition of roots is not known. In the present
      study, we compared the mechanism in the hypergravity-induced growth inhibition of
      roots with that in gravitropism. The removal of root cap did not influence
      hypergravity-induced growth inhibition of roots, although the gravitropic
      curvature was completely inhibited. Hypergravity had no effects on growth of
      azuki bean roots in the presence of lanthanum or gadolinium, which are blockers
      of mechanoreceptors. On the contrary, lanthanum or gadolinium at the same
      concentration did not influence gravitropism of roots. These results suggest that
      the graviperception mechanism in the hypergravity-induced growth inhibition of
      roots is independent of that in gravitropism. Hypergravity-induced growth
      inhibition of azuki bean roots was observed irrespective of the direction of
      stimuli, which disappeared in the presence of lanthanum or gadolinium. Thus, in
      the hypergravity-induced growth inhibition, roots may perceive the gravity signal
      by mechanoreceptors on the plasma membrane independently of the direction of
      stimuli, and may utilize it to regulate their growth rate.

PMID- 14676364
TI  - Effect of gravity on apical dominance in Pharbitis nil.
AB  - When the upper part of main shoot of morning glory (Pharbitis nil) is gently bent
      down, lateral bud on the bending region is released from apical dominance and
      starts to elongate. But, clinorotating the bending shoots prevents the release of
      the lateral bud from apical dominance. These results suggest that gravity affects
      apical dominance in morning glory. Here we verified the gravity-regulated apical
      dominance by using a weeping morning glory defective in gravitropic response due
      to abnormal differentiation of endodermis. That is, bending main shoot of the
      weeping morning glory hardly caused the lateral bud to elongate. In addition,
      decapitation of apical bud released the lateral bud from apical dominance, and
      exogenous auxin applied to the cut surface of the decapitated stem was inhibitory
      to the outgrowth of the lateral bud in the wild type. However, the effect of
      auxin was much less in the weeping morning glory. Thus, apical dominance of the
      weeping morning glory was weaker and less influenced by gravity than that of the
      wild type, which could occur due to abnormal differentiation of endodermis
      required for graviperception.

PMID- 14676363
TI  - The effect of light on the gravimorphogenesis of cucumber seedlings.
AB  - Light affects the responses of plants to gravity. For example, light is
      inhibitory to the gravimorphogenesis of cucumber seedlings, peg formation. We
      have suggested that auxin regulates peg formation by stimulating the expression
      of auxin-inducible genes including CsACS1 that encodes key enzyme in ethylene
      synthesis. We also have hypothesized that ethylene promotes the development of
      peg in cucumber seedlings. To understand how light inhibits peg formation, we
      examined the effects of light on the auxin-induced peg formation, the expression
      of auxin-inducible genes and ethylene production in cucumber seedlings. Number of
      seedlings that produced a peg in response to applied IAA was significantly
      decreased by exposure to light compared with that in the dark. In addition,
      exposure of seedlings to light decreased mRNA accumulation of CsACS1 and ethylene
      production. However ethylene application did not compensate the inhibition of peg
      formation by light. These results suggest that light blocks auxin-mediated
      step(s) including CsACS1 expression for the initiation of peg formation.

PMID- 14676365
TI  - LET and ion-species dependence for cell killing and mutation induction in normal
      human fibroblasts.
AB  - We have been studying LET and ion species dependence of RBE values in cell
      killing and mutation induction. Normal human skin fibroblasts were irradiated
      with heavy-ion beams such as carbon (290 Mev/u and 135 Mev/u), neon (230 Mev/u
      and 400 Mev/u), silicon (490 Mev/u) and iron (500 Mev/u) ion beams, generated by
      Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of
      Radiological Sciences (NIRS). Cell killing effect was detected as reproductive
      cell death using a colony formation assay. Mutation induction in hprt locus was
      detected to measure 6-thioguanine resistant colonies. The RBE-LET curves of cell
      killing and mutation induction were different each ion beam. So, we plotted RBE
      for cell killing and mutation induction as function of Z*2/beta2 instead of LET.
      RBE-Z*2/beta2 curves of cell killing indicated that the discrepancy of RBE-LET
      curves was reconciled each ion species. But RBE-Z*2/beta2 curves of mutation
      induction didn't corresponded between carbon- and silicon-ion beams. These
      results suggested that different biological endpoints may be suitable for
      different physical parameter, which represent the track structure of energy
      deposition of ion beams.

PMID- 14676366
TI  - Loss of heterozygosity in heavy-ion-induced murine T-cell lymphomas.
AB  - One of the important concerns for astronauts in space environment is cancer risk
      associated with cosmic radiation, including heavy particle carbon-ions. But
      little information on cancer risk is available. In the present study, we
      investigated the induction of and cellular and molecular characteristics of T
      cell lymphomas of B6C3F1 mice induced by carbon-ions and X-rays. The incidence,
      the latent period and the surface expression of T-cell differentiation antigens
      were similar between carbon-ion- and X-ray-induced lymphomas. The size of T-cell
      lymphomas induced by carbon-ions was significantly smaller than that by X-rays.
      Molecular analysis indicated that high frequency of loss of heterozygosity (LOH)
      was found on chromosomes 4, 11, 12 and 19 in both lymphomas. Interestingly, the
      frequency of LOH on chromosome 11 was much higher, but that on chromosome 12 was
      lower in carbon-ion-induced T-cell lymphomas than in X-ray-induced ones. These
      results indicate that mechanistic differences may exist between carbon-ion- and X
      ray-induced lymphomagenesis.

PMID- 14676367
TI  - Formation of organic compounds from simulated Titan atmosphere: perspectives of
      the Cassini mission.
AB  - Gas mixtures of methane and nitrogen were subjected to proton irradiation (PI),
      gamma irradiation (GI), UV irradiation (UV) or spark discharges (SD), and the
      products were analyzed to compare possible energy sources for synthesis of
      organics in Titan. SD mainly gave unsaturated hydrocarbons, while PI gave
      saturated hydrocarbons. N-containing organics were detected in PI, GI and SD, but
      not in UV. The formers yielded amino acids after acid-hydrolysis of solid phase
      products (tholin). Comparison of the present results with those by Cassini
      Huygens [correction of Heygens] mission will make it possible to prove major
      energy sources for organic synthesis in Titan atmosphere.

PMID- 14676368
TI  - Organics in chimneys and water samples from deep-sea hydrothermal systems:
      implications for sub-vent biosphere.
AB  - Searching for life in extreme terrestrial environments can be a model of that for
      extraterrestrial life. Submarine hydrothermal system is one of promising sites
      for the frontier of life on the earth. Here seawater and vent chimnies were
      collected from deep-sea hydrothermal vents at Suiyo Seamount, Izu-bonin arc,
      Pacific Ocean as a part of Archaean Park Project. Pure seawater sample of 300
      degrees C (purity>97%) could be collected. Dissolved and total hydrolyzable amino
      acids were determined by ion-exchange HPLC, and their enantiomeric ratio was
      measured by reversed-phase HPLC for the first time. Glycine and serine were two
      most abundant amino acids, followed by other proteinous amino acids such as
      alanine, glutamic acid and aspartic acid. Non-proteinous amino acids were
      detected as minor constituents. Most of the amino acids detected were of the L
      form. Thus amino acids of abiotic origin were quite minor, and most of the amino
      acids detected were formed biologically. These results, together with analytical
      results of the vent chimney samples, suggest that there is active microbial
      activities near the hydrothermal systems.

PMID- 14676369
TI  - Pyrolysis experiment of simulated exogenous complex organics synthesized from the
      gas mixtures of CO, NH3, and H2O by 3 MeV proton irradiation.
AB  - High molecular weight organic matter synthesized from mixtures of carbon
      monoxide, ammonia and water gases similar to those found in the interstellar
      medium were irradiated with a 3 MeV proton beam and analyzed by Curie point
      pyrolysis with detection by gas chromatograph and mass spectrometer (Pyr-GC-MS).
      A wide variety of organic compounds, not only a number of amide compounds, but
      also heterocyclic and polycyclic aromatic hydrocarbons (PAHs), were detected
      among the products of the pyrolysis. The present data shows that primary and
      primitive organic matter serving as  precursors  to bioorganic compounds such as
      amino acids, nucleic acid bases and sugar might have been formed in a gaseous
      mixture of similar composition to that of the interstellar dust environment.

PMID- 14676370
TI  - Evaluation of cell culture flasks designed for experiment under altered gravity
      vector conditions.
AB  - Cell culture flasks applicable for altered gravity conditions, such as
      centrifugation, clino-rotation or microgravity in space, were manufactured for
      trial. The flask has flat polystyrene surface for monolayer culture and gas
      permeable film window on the opposite face. The space in-between consists the
      culture chamber to be filled with liquid medium. To reduce the water loss and
      bubble formation in the culture fluid, another gas permeable window was placed on
      top to form a space where distilled water may be filled. The double-decker
      culture flask can be used for both space and ground-based experiments in common.

PMID- 14676371
TI  - Ground based verification of JAXA hardware for life science experiments.
AB  - Japanese new space agency (merger of NASDA, ISAS and NAL), JAXA (Japan Aerospace
      Exploration Agency) has been developing the Plant Experiment Unit (PEU) and the
      Cell Experiment Unit (CEU), which will be used within the Cell Biology Experiment
      Facility (CBEF) in "Kibo" Japanese Experiment Module (JEM) of ISS. They can also
      be operated within the Clean Bench (CB) in Kibo. We report the preliminary
      results of ground based verification experiments using the PEU and the CEU. Six
      units of PEU/CEU in microgravity section and 4 units of PEU/CEU in control-g
      section, will be operated within CBEF.

PMID- 14676372
TI  - Embryogenesis and swimming behavior of Medaka fish in JUSTSAP STARS Program (STS
      107).
AB  - JUSTSAP (Japan-US Science, Technology and Space Application Program) Medaka fish
      experiment was carried out as a part of STARS (Space Technology and Research for
      Student) experiment, a space shuttle mission, STS-107 in January 2003. Four eggs
      laid on earth under artificially controlled environment were put in a closed
      ecological system, AHAB (Aquatic Habitat), and launched by Space Shuttle
      Columbia. For the control experiment, four eggs were put in the AHAB and remained
      on the ground. There was no remarkable difference in the time course of the
      development. In ground experiment embryos were observed to rotate in the egg
      membrane, whereas in flight unit they did not rotate. One egg hatched out on L
      (Launch) +8 days in flight unit. Four eggs hatched out in ground unit. Fry in
      flight unit was observed to face its back usually to the camera with little
      swimming movement. Fry in ground unit were observed to move actively and also to
      control their posture with respect to gravity vector.

PMID- 14676373
TI  - Effect of resistance training on changes in lymphocyte subpopulation during head
      down-tilt bed rest.
AB  - Head-down-tilt (HDT) bed rest imitates microgravity-like conditions for a supine
      human body on the ground. On the other hand, resistance training is used to
      eliminate unfavorable physical changes in astronauts under a microgravity
      environment during spaceflight. Twelve healthy males voluntarily participated in
      a 20-day -6 degrees HDT bed rest study. The ratio of CD3-positive peripheral
      blood lymphocytes were analyzed by immunofluorescence staining. Volunteers who
      undertook resistance-training during HDT bed rest were designated as the
      resistance training group (RTG), and those who did not as non-resistance-training
      group (N-RTG). We could not observe significant differences in the ratio of CD3
      positive peripheral blood lymphocytes between RTG and N-RTG. Thus, resistance
      training during HDT bed rest might not have a significant effect on changes in
      the ratios of CD3-positive PBL.

PMID- 14676374
TI  - Effects of gravitational loading on rat soleus muscle fibers following hindlimb
      suspension.
AB  - Effects of 16 days of hindlimb suspension and 16 days of ambulation recovery at 1
      G or 2-G environment on the characteristics of soleus muscle fibers were studied
      in male Wistar Hannover rats. The mean cross-sectional area and myonuclear number
      in isolated single fibers at the termination of suspension were approximately 30%
      and 25% of the controls, respectively. Satellite cells were distributed evenly
      throughout the fiber length in the control. However, the number of satellite
      cells distributed at the middle of the fiber was less in the unloaded rats
      immediately after the termination of suspension. Both the numbers of quiescent
      and mitotic active satellite cell per fiber were approximately 57% less
      immediately after the termination of suspension than controls. The number of
      satellite cells at the end of fibers was increased first during the early phase
      of reloading. Subsequently, the number at the middle was gradually increased. The
      myonuclear number per fiber was also less (approximately 25%) in the unloaded
      than the age-matched control at the termination of suspension, but was increased
      following the recovery. Although the mean in vivo sarcomere length of the soleus
      muscle was shortened in response to plantarflexion of ankle joint, the length at
      the certain ankle joint angle was increased after 16 days of suspension due to
      sarcomere remodeling. The length at the proximal and distal, rather than the
      middle, portion of the fiber was stretched in both reloaded and control rats in
      response to dorsiflexion of the ankle joint. But it was noted that the magnitude
      of stretch was greater in the unloaded rats. It is suggested that the fiber end
      is more stimulated rapidly than the middle portion by the load applied to the
      muscle during the ambulation recovery.

PMID- 14676375
TI  - R-R interval variability with lower body positive pressure assessed by wavelet
      packet transform.
AB  - Lower body positive pressure (LBPP) is used for simulation of microgravity due to
      central fluid shift. In the present study, we evaluate R-R interval variability,
      which is sometimes considered as an index of human cardiovascular autonomic nerve
      status. 10 healthy male subjects were set in a chamber with standing position.
      Chamber pressure was raised 10 mmHg each for every 3 minutes, up to +40 mmHg.
      Wavelet packet transform (WPT) followed by Hilbert transform was employed to
      analyze time-dependent changes in low frequency component (LF) and high frequency
      component (HF) of R-R interval variability. Calf circumference lowered according
      to chamber pressure. ABP was maintained throughout measurements. R-R interval was
      significantly higher at +30 and +40 mmHg compared to that of control. Standing
      LBPP causes higher HF and lower L/H probably due to central fluid shift, and WPT
      followed by Hilbert transform shows time-dependent changes in R-R interval
      variability.

PMID- 14676376
TI  - Cerebral hemodynamics during microgravity.
AB  - As one of the causes of the space adaptation syndrome, an increased intracranial
      pressure due to the cephalad fluid shift is suggested. In the present study, we
      measured intracranial pressure (ICP), aortic pressure and cerebral flow velocity
      (CFV) in anesthetized rats (n=5) during 4.5 sec of microgravity induced by free
      drop. The rats were set at horizontal prone (Flat) and 30-degree head-up whole
      body tilting (HU) positions to examine the effect of gravitational pressure
      gradient. Then, arterial pressure at the eye level (APeye), cerebral perfusion
      pressure (CPP; CPP=APeye-ICP), and CPP-CFV relationship was calculated. In HU
      position, ICP, APeye, and CPP increased by 2.2 +/- 0.4, 12.3 +/- 2.0, and 10.1 +/
      1.7 mmHg respectively. However, CFV did not change significantly. In Flat
      position, none of these variables did not change significantly. In HU position
      the slope of CPP-CFV relationship decreased, suggesting the increased cerebral
      flow resistance. However, it did not change in Flat position. These results can
      be understood by the disappearance of gravitational pressure gradient by
      microgravity and the cerebral autoregulation.

PMID- 14676377
TI  - The content of heat shock protein 47 (HSP47), a collagen-specific stress protein,
      changes with gravitational conditions in skeletal muscle.
AB  - It is well known that unloading of skeletal muscle with spaceflight or tail
      suspension leads rat soleus muscle atrophy. Previously, we reported that one of
      small heat shock protein (sHSP), alpha B-crystallin shows an early dramatic
      decrease in atrophied rat soleus muscle (Atomi et al, 1991). In this report, we
      focused to study the gravitational responses of another HSP, which may be
      reactive to the gravity. HSP47, a collagen-specific stress protein, has been
      postulated to be a collagen-specific molecular chaperone localized in the ER
      (Nagata et al, 1992). Western blot analysis revealed that HSP47 in slow skeletal
      muscle decreases at 5 days after tail suspension (TS) and increased at 5 days
      recovery after 10 days of TS as compared with the control level. Hypothetically,
      HSP47 in slow soleus muscle increases at 5 days after hypergravity (HG) induced
      by the centrifugation. The content of HSP47 in soleus muscle was strongly
      affected by gravity conditions.

PMID- 14676378
TI  - Experiment of seed germination with low pressure environment simulator.
AB  - Seeds of Brassica campestris germinated in low pressure environment at the
      pressures of 100, 50, 30, 20 kPa. The germination rates of 7 days after seeding
      were more than 90% without the rate at the pressures of 20 kPa. As the pressure
      was less, the germination was slower. The results showed that seeds of Brassica
      campestris normally germinated at the pressure of more than 30 kPa. The
      germination rate at the pressures of 20 kPa was about 60%. The germination rate
      was not normal. However, it was possible to germinate. The germination at the
      pressure of less than 20 kPa is expected.

PMID- 14676379
TI  - Novel hydrotropism mutants of Arabidopsis thaliana and their altered waving
      response and phototropism.
AB  - Roots display positive hydrotropism in response to a moisture gradient, which is
      important for plants to escape from water stress and regulate the directional
      growth by interacting with other growth movements such as gravitropism,
      phototropism and waving response. On Earth, hydrotropism is interfered by
      gravitropism in particular, so that microgravity conditions or agravitropic
      mutants have been used for the study of hydrotropism. However, we have recently
      established an experimental system for the study of hydrotropism in Arabidopsis
      roots that easily develop hydrotropism in response to moisture gradient by
      overcoming gravitropism. Using the Arabidopsis system, we isolated hydrotropism
      mutants named root hydrotropism (rhy). In the present study, we examined the
      hydrotropism, gravitropism, phototropism, waving response and elongation growth
      of rhy4 and rhy5 roots that were defective in positive hydrotropism.
      Interestingly, rhy4 roots curved away from the water source and showed a reduced
      waving response. Both rhy4 and rhy5 showed normal gravitropism and a slight
      reduction in phototropism. These results suggest that there is a mutual molecular
      mechanism underlying hydrotropism, waving response and/or phototropism. Thus, we
      have obtained novel hydrotropic mutants that will be used for revealing molecular
      mechanism of root hydrotropism and its interaction with waving response and/or
      phototropism.

PMID- 14676380
TI  - Pistil and stamen of lily flowers bend upward by light.
AB  - Pistil and stamen of lily flowers bend upward. Such tropic response at sensing
      external stimuli increases the success of pollination in these flowers and
      improve their adaptability. They do not bend under the dark, but toward light
      irradiated. From these observation, lily flowers is concluded that they equip
      phototropic mechanism to sense direction of incident light and control
      differential elongation of pistil and stamen. Action spectrum of light for this
      tropism was found similar to those for the phototropism shown in coleoptiles of
      monocotyledonous plants. Image analysis of pistil and stamen indicates that
      elongation and bending does not proceed uniformly over those organs. In the case
      of pistil, elongation starts at its basal part and propagates towards its top
      after opening of perianth. Steep bending occurs at the basal zone of pistil as
      long as differential incidence of light is given at its part.

PMID- 14676381
TI  - Volatile allelopathy in velvet bean (Mucuna pruriens [correction of pruiens] L.)
      and gravity.
AB  - Allelopathy caused by volatile compounds was studied with velvet bean (Mucuna
      pruriens [correction of prueiens] L.). Preparatory experiment was conducted to
      identify the relationship between action of volatiles and gravity. The
      experimental protocol was defined and tested to study on volatile allelopathy of
      velvet bean. Root growth of lettuce (Lactuca sativa L.) seedlings was inhibited
      by volatile gas from velvet bean seedlings planted in Agripot. In this study, it
      was shown that ten-day velvet bean seedling could exhibit the volatile
      allelopathic ability. Growth chambers for volatile experiment were designed.
      Velvet bean seed can germinate in a 3-ml small vial.

PMID- 14676382
TI  - Growth of endophyte (Neotyphodium) during seed germination of tall fescue
      (Festuca arundinacea).
AB  - Growth of a filamentous fungus endophyte, Neotyphodium, was examined during the
      seed germination process of its host plant, tall fescue, Festuca arundinacea, by
      the ELISA method. Distribution of endophyte differed from that of substances
      induced by endophyte.

PMID- 14676383
TI  - Effects of high gravity on amphibian development.
AB  - In order to clarify the possible effects of high gravity environments on eggs and
      developing embryos, Rana rugosa and Xenopus laevis fertilized eggs and early
      embryos were raised in 2 G, 5 G, 7 G and 10 G up to the hatched tadpole stage.
      The results showed that: (1) High gravity significantly retarded the development
      of eggs and embryos beginning treatment before the blastula stage and induced
      various abnormalities, including two heads and microcephally suggesting that high
      gravity is apt to disrupt the animal-vegital axis. On the other hand, embryos
      beginning treatment after the gastrula stage showed a striking increase in the
      number of normal-appearing feeding tadpoles. (2) Autopsy revealed that brains,
      notochords and muscles were reduced in development and differentiation for
      embryos and tadpoles developed in high gravity. (3) It seems likely that the
      system for hydrogen peroxide detoxification develops abnormally in high gravity
      treated embryos and tadpoles, which probably results in oxidative stress, leading
      to considerable cell damage.

PMID- 14676384
TI  - Effects of gravity on early embryogenesis [correction of embryogeneis] in
      Caenorhabditis elegans.
AB  - The embryonic development of the nematode Caenorhabditis elegans was examined
      under different gravitational conditions. The embryos after fertilization
      normally hatched under hypergravity (200 G) or 3D-clinorotation, whereas the
      number of eggs laid from an adult hermaphrodite decreased and their hatching rate
      was reduced under the hypergravity condition. The first cleavage plane in the 1
      cell embryo was slid to some extent by re-orientation of liquid culture vessel,
      but the pattern and timing of cleavages were not affected.

PMID- 14676385
TI  - Changes in food intake and growth rate in mice under hypergravity.
AB  - Mice exposed to hypergravity, especially soon after start of exposure, diminished
      the body weight and the food intake. The amount of food intake was kept less than
      that of the ground control during hypergravity breeding for 2 weeks. Furthermore,
      the weight of testis relative to the body weight increased compared to that of 1
      G control although the relative weights of liver and kidney were not changed. The
      purpose of this study was whether the low growth rate of the body weight and the
      increase of the relative testis weight were induced by the decrease of the food
      intake under hypergravity. We divided 3 weeks old male mice to 3 groups; the 1 G
      (ground control), the food restricted (FR) under 1 G, and the 3 G group. The 3 G
      group bred for 2 weeks under the centrifuge at 3 G. The FR group was given the
      same amount of food as the group ate. The changes in the body weight and the
      relative weights of testis, spleen and seminal vesicle of the FR group were
      similar to those of the 3 G group. The hunger test revealed that only the FR
      group was hunger. Our results suggested that the decrease of the food intake both
      in response to hypergravity and the food restriction induced the decrease of the
      body weight but the increase of the relative testis weight.

PMID- 14676386
TI  - Effects of adrenaline and cortisone on the early activation of lymphocytes.
AB  - Using whole blood, we examined the effects of stress hormones on CD69 expression
      in Natural Killer (NK) cells. A series of diluted adrenaline or cortisone was
      added to 1 ml of whole blood. Propranolol was used to block the beta-adrenergic
      effect. The blood samples were activated with CD2/CD2R mitogenic antibody
      solution for four hours under 37 degrees C. Then CD69 antigen on NK cells was
      analyzed by flowcytometric assay. Adrenaline and cortisone doses dependently
      suppressed CD69 expression on NK cells. Propranolol blocked the suppressive
      effect of adrenaline. CD69 expression was significantly higher than the control
      when only propranolol was added. We concluded that blood constituents acting on
      mitogenic reaction and stress hormones affect the early stage on the way to
      proliferation and differentiation.

PMID- 14676387
TI  - Effects of parabolic flight on abdominal arterial pressure in conscious rats.
AB  - Abdominal arterial pressure during parabolic flight was measured using a
      telemetry system to clarify the acute effect of microgravity on hemodynamics in
      conscious rats. The microgravity condition was elicited by three different levels
      of entry gravity, i.e. 2 G, 1.5 G and 1 G. On exposure to 2 G, mean aortic
      pressure (MBP) increased up to 118.7 mm Hg +/- 7.3 compared with the value at 1 G
      (107.0 +/- 6.3 mm Hg, n=6). The value at microgravity preceded by 2 G was 118.0
      mmHg +/- 5.2 mm HG and it was still higher than at 1 G. When 1.5 G was elicited
      before microgravity exposure, MBP also increased (1.5 G: 114.9 +/- 5.3 vs 1 G:
      105.8+/-5.0 mm Hg) and the value at microgravity was 117.3 + /- 5.3 mmHg. During
      pre-microgravity maneuver with 1 G, no changes were observed compared with the
      control level at 1 G (pre-microgravity: 105.0 +/- 5.0 vs 1G: 104.8 +/- 5.1 mm Hg
      ), whereas the MBP increased up to 117.0 +/- 6.5 mm Hg on exposure to
      microgravity. From these results, we found that in conscious rat MBP increase
      during acute microgravity exposure with either 1 G or hyper-G entry.

PMID- 14676388
TI  - Changes of bone morphology in response to hindlimb suspension of rats.
AB  - Effects of chronic hindlimb suspension or exposure to 2-G from postnatal day 4 to
      month 3 followed by ambulation recovery on the floor on the morphology of
      hindlimb bones were investigated in rats. The dorsi-flexion of the ankle was
      inhibited in the suspended group and such phenomena were not recovered at all.
      The mean weight and length of femur, tibia, and fibula were less than the cage
      controls at the end of suspension, but gradually increased during recovery.
      However, they were still less than those of the age-matched controls even after 3
      month recovery. External bending of shaft and rotation of distal end of tibia
      were observed in the suspended group and these phenomena were not recovered at
      all. These morphological changes caused the inhibition of dorsi-flexion of ankle
      joints. The electromyogram activities of ankle plantar-flexors, soleus,
      plantaris, lateral gastrocnemius, were inhibited and those of dorsi-flexor,
      tibialis anterior, were increased during suspension. Typical changes in bone
      morphology were not induced by exposure to 2-G. It was suggested that
      gravitational unloading during developing period causes irreversible inhibition
      of normal bone growth. It was also indicated that the suspension-related changes
      in bone morphology may be caused by abnormal mechanical stress due to the altered
      mobilization of hindlimb muscles.

PMID- 14676389
TI  - Skin blood flow with elastic compressive extravehicular activity space suit.
AB  - During extravehicular activity (EVA), current space suits are pressurized with
      100% oxygen at approximately 222 mmHg. A tight elastic garment, or mechanical
      counter pressure (MCP) suit that generates pressure by compression, may have
      several advantages over current space suit technology. In this study, we
      investigated local microcirculatory effects produced with negative ambient
      pressure with an MCP sleeve. The MCP glove and sleeve generated pressures similar
      to the current space suit. MCP remained constant during negative pressure due to
      unchanged elasticity of the material. Decreased skin capillary blood flow and
      temperature during MCP compression was counteracted by greater negative pressure
      or a smaller pressure differential.

PMID- 14676390
TI  - Modification of cell wall architecture of wheat coleoptiles grown under
      hypergravity conditions.
AB  - Cell wall structure of wheat coleoptiles grown under continuous hypergravity (300
      g) conditions was investigated. Length of coleoptiles exposed to hypergravity for
      2-4 days from germination stage was 60-70% of that of 1 g control. The amounts of
      cell wall polysaccharides substantially increased during the incubation period
      both in 1 g control and hypergravity-treated coleoptiles. As a results, the
      levels of cell wall polysaccharides per unit length of coleoptile, which mean the
      thickness of cell walls, largely increased under hypergravity conditions. The
      major sugar components of the hemicellulose fraction, a polymer fraction
      extracted from cell walls with strong alkali, were arabinose (Ara), xylose (Xyl)
      and glucose (Glc). The molar ratios of Ara and Xyl to Glc in hypergravity-treated
      coleoptiles were higher than those in control coleoptiles. Furthermore, the
      fractionation of hemicellulosic polymers into the neutral and acidic polymers by
      the anion-exchange column showed that the levels of acidic polymers in cell walls
      of hypergravity-treated coleoptiles were higher than those of control
      coleoptiles. These results suggest that hypergravity stimuli bias the synthesis
      of hemicellulosic polysaccharides and increase the proportion of acidic polymers,
      such as arabinoxylans, in cell walls of wheat coleoptiles. These structural
      changes in cell walls may contribute to plant resistance to hypergravity stimuli.

PMID- 14676391
TI  - Isolation of auxin efflux carrier cDNA from cucumber.
AB  - Cucumber seedlings display not only gravitropism but also peg formation in
      response to gravity. Gravimorphogenesis is mediated by auxin distribution. As
      first step to reveal the mechanism that regulates auxin distribution by auxin
      efflux, we isolated five partial cDNAs of auxin efflux carriers by RT-PCR method.
      In addition, we isolated two full-length cDNAs (CsPIN2, CsPIN3) from a cucumber
      cDNA library. CsPIN2, AtPIN3, AtPIN4 and AtPIN7 fall within the same clade.
      CsPIN3, AtPIN1 and CsPIN1 fall within the same clade. CsPIN5, CsPIN6 and AtPIN2
      fall within the same clade. Our phylogenetic analysis of PIN in cucumber and
      Arabidopsis indicates that cucumber may diversify CsPIN protein compared with
      AtPIN protein.

PMID- 14676392
TI  - Identification of the cDNA of differentially expressed genes in the transition
      zone of cucumber seedlings by fluorescent differential display.
AB  - Cucumber seedlings have potential to develop two pegs on the transition zone
      between the hypocotyl and root. Seedlings grown in a horizontal position suppress
      the development of the peg on the upper side of the transition zone in response
      to gravity. To understand how the response to gravity suppresses peg formation,
      we screened cucumber mRNAs to identify the mRNA in the non-peg side that
      accumulates more than in the peg side. For screening, we determined conditions of
      fluorescent differential display (FDD). Then, we carried out FDD and found 4 cDNA
      bands that repeatedly showed stronger intensity in the non-peg side than the peg
      side. We isolated one of these RT-PCR products. Northern blotting showed the
      pattern of its mRNA accumulations corresponding to the results of FDD.

PMID- 14676393
TI  - Graviresponse and its regulation from the aspect of molecular levels in higher
      plants: growth and development, and auxin polar transport in etiolated pea
      seedlings under microgravity.
AB  - In STS-95 space experiments we have demonstrated that microgravity conditions
      resulted in automorphosis in etiolated pea (Pisum sativum L. cv. Alaska)
      seedlings (Ueda et al. 1999). Automorphosis-like growth and development in
      etiolated pea seedlings were also induced under simulated microgravity conditions
      on a 3-dimensional (3-D) clinostat, epicotyls being the most oriented toward the
      direction far from the cotyledons. Detail analysis of epicotyl bending revealed
      that within 36 h after watering, no significant difference in growth direction of
      epicotyls was observed in between seedlings grown on the 3-D clinostat and under
      1 g conditions, differential growth near the cotyledonary node resulting in
      epicotyl bending of ca. 45 degrees toward the direction far from the cotyledons.
      Thereafter epicotyls continued to grow almost straightly keeping this orientation
      on the 3-D clinostat. On the other hand, the growth direction in etiolated
      seedlings changed to antigravity direction by negative gravitropic response under
      1 g conditions. Automorphological epicotyl bending was also phenocopied by the
      application of auxin polar transport inhibitors such as 9-hydroxyfluorene-9
      carboxylic acid, N-(1-naphtyl)phthalamic acid and 2,3,5-triiodobenzoic acid.
      These results together with the fact that auxin polar transport activity in
      etiolated pea epicotyls was substantially reduced in space suggested that reduced
      auxin polar transport is closely related to automorphosis. Strenuous efforts to
      learn how gravity contributes to the auxin polar transport in etiolated pea
      epicotyls in molecular bases resulted in successful identification of PsPIN2 and
      PsAUX1 encoding putative auxin-efflux and influx carrier proteins, respectively.
      Based on the results of these gene expression under simulated microgravity
      conditions, a possible role of PsPIN2 and PsAUX1 genes for auxin polar transport
      in etiolated pea seedlings will be discussed.

PMID- 14676394
TI  - Studies on vestibular organs in the fry of mutant Medaka.
AB  - We provide an overview of the features of vestibular organs, especially of
      otolith organs in mutant Medaka ha. The ha fish have a dysfunction in sensing
      gravity due to the absence of utricular otoliths either unilaterally or
      bilaterally. Especially in their early developmental stages, the posture control
      is predominantly depend on light rather than on gravity seen in the wild-type.
      The ha juveniles that were kept and tolerated in an environment with altered
      light directions indicated a strong light dependency on the posture maintenance,
      while the fish under an ordinary light environment gradually changed their
      posture control by sensing light to gravity around 30 days after hatching and
      beyond. Their behavior under microgravity agreed with such phenomena observed in
      ground laboratory.

PMID- 14676395
TI  - Behavior of Medaka fish under distributed gravity.
AB  - The threshold value of gravity for Medaka fish (Oryzias latipes) was determined
      using parabolic flights of an airplane. Rotating a turntable during a 20 sec of
      microgravity, a gradient field of centrifugal force was realized in the aquarium.
      Fish of HO5 strain were used because from the previous studies, in microgravity
      they were known to exhibit looping behavior more easily than any other strains.
      Looping fish became stable (i.e., recovered their posture control) when fish swam
      from a lower-gravity area of the aquarium to an area of a certain gravity value
      or beyond. On the other hand, stable fish lost their posture control and started
      looping when fish swam into an area of a gravity lower than a certain value.
      Using these phenomena, we obtained the gravity value of 0.21 to 0.26 G as for the
      threshold value for Medaka fish to sense the gravity.

PMID- 14676396
TI  - Developmental status of Aquatic Animal Experiment Facility, Aquatic Habitat
      (AQH), for International Space Station.
AB  - Mitsubishi Heavy Industries (MHI) and Japan Aerospace Exploration Agency (JAXA)
      have been studying Aquatic Animal Experiment Facility, Aquatic Habitat (AQH), for
      International Space Station (ISS). The AQH will have the capabilities to
      accommodate small freshwater fish and amphibian for maximum 90 days on orbit.
      Three-generations of small freshwater fish (medaka and zebrafish), and egg
      through metamorphosis of amphibian (African clawed toad) could be experimented by
      AQH. Various experimental functions such as automatic feeding, air-water
      interface, day/night cycle, video observation, and specimen sampling mechanism
      will be also equipped in AQH. The water circulation system was improved from the
      past aquatic facilities for Space Shuttle experiments under the consideration of
      the long life-time, and a brand-new specimen chamber was developed to equip the
      above various experimental functions. Currently the prototype model of water
      circulation system and specimen chambers have been manufactured and biological
      compatibility tests are being conducted with medaka. The current developmental
      status of AQH is summarized.

PMID- 14676397
TI  - Point of a space experiment proposal.
AB  - JAXA will solicit research proposals for space flight experiments that would be
      conducted for less than three years after the selection. In principle, available
      samples will be limited to Arabidopsis and C. elegans and flight hardware and
      protocol of space flight experiment will be pre-fixed. Proposals using different
      combinations of species and flight hardware will not be acceptable. Besides
      scientific issues, it is very important for proposer to write an impressive
      proposal. Hypothesis basis research proposal is the accepted standard. Reviewers
      will dislike a descriptive and unfocused research proposal without hypothesis.
      Ground preparation experiments, which are not related directly to space
      experiments, should not be included in the solicitation.

PMID- 14676398
TI  - Physiological and genetic characterization of hydrotropic mutants of Arabidopsis
      thaliana.
AB  - Roots display positive hydrotropism in response to moisture gradient.
      Hydrotropism regulates the directional growth by interaction with other growth
      movements. Using the seedlings of pea, cucumber, maize and wheat, we have
      revealed that the root cap perceives the moisture gradient and that auxin and
      calcium are involved in hydrotropism. However, molecular mechanisms for stimulus
      perception or signal transduction in hydrotropism are still remained unrevealed.
      To dissect the molecular mechanism underlying hydrotropism in seedling roots, we
      established a method for screening Arabidopsis mutants defective in root
      hydrotropism. Among about 20,000 M2 seedlings of Arabidopsis plants treated with
      EMS, we successfully obtained 12 mutants of which root hydrotropism was reduced
      to various extents. We named them root hydrotropism (rhy) and examined their
      gravitropism, phototropism, waving response and elongation growth as well as
      hydrotropism in roots. Roots of rhy1 mutant showed ahydrotropic response although
      the other responses and elongation growth of rhy1 mutant were normal. Roots of
      rhy2 and rhy3 mutants showed a reduced hydrotropism and abnormal responses in
      gravitropism, phototropism or waving pattern. Genetic analysis of the progeny
      produced by the backcross of rhy1 mutant to wild type suggested that rhy1 was a
      recessive mutation. We also examined the map position of the rhy1 locus.

PMID- 14676399
TI  - Gravitational and hormonal control in secondary xylem formation of Japanese
      flowering cherry.
AB  - It has been reported that Japanese flowering cherry promotes the formation of
      tension wood in the upper side of the inclined stem, which induces the negative
      gravitropism. In the other hand, the plant under simulated micro-gravity
      conditions reduces the width of the secondary xylem and increases the density of
      the vessels, which means decreased the density of the fiber cells. The plant
      under simulated micro-gravity conditions showed that the inhibition of xylem
      development and the decreased supporting mechanism in the stem. In this study we
      examined that the effects of auxin and gibberellin in the plant under simulated
      micro-gravity conditions and inclined stimulus. The gibberellin treatment
      promotes the secondary xylem development under simulated microgravity conditions
      and inclined stimulus. The upper side of the inclined stem contents much higher
      levels of IAA and gibberellin A1(GA1) than the lower side of that.

PMID- 14676400
TI  - The growth movement in the peduncle of Eichhornia crassipes II.
AB  - The peduncle of water hyacinth (Eichhornia crassipes) showed the downward bending
      within 24 hours after full flowering. Previously it was suggested that the
      downward bending of peduncle might be induced by the differential growth of the
      epidermal cells of the portion because of the differential distribution of auxin
      in the upper side of the bending part of the peduncle. In order to investigate
      the effect of auxin and gravity on the peduncle bending in Water hyacinth, we
      examined the growth reaction of peduncle and the effects of plant hormones on the
      bending of peduncle under simulated microgravity, and the sedimentable amyloplast
      on earth and three dimensional (3D)-clinostat. As a result it was confirmed that
      the downward bending of peduncle in water hyacinth is the positive gravitropism,
      and that its phenomenon is caused by the differential distribution of auxin in
      the upper side of bending part of peduncle. It was found that the amyloplast
      sediments toward gravity direction in the bending part of the peduncle. From the
      present results, any direct relation between the sedimentable amyloplast and
      auxin transport were not cleared in the peduncle of water hyacinth. Further study
      should be carried out.

PMID- 14676401
TI  - Proteome analysis of glial cells treated by radiation or hydroperoxide.
AB  - Reactive oxygen species (ROS) give rise to various types of oxidative damage and
      some responses such as activation of transcription factors and/or repair factors
      in cells. Proteome analysis using 2-D PAGE and peptide mass fingerprinting is
      suitable for the study on the post-translational modifications of proteins. When
      glial cells were exposed to hydroperoxide, the relative abundance of 9 spots
      changed on 2-D gels, as compared with control gels. MALDI-TOF MS analysis after
      in-gel digestion revealed that these spots corresponded to at least 3 pairs of
      proteins. These pairs of protein spots had different isoelectric points each
      other and were identified as peroxiredoxin II, peroxiredoxin III and calpactin I
      light chain. It was demonstrated that peroxiredoxins II and III were oxidized to
      their acidic forms (acidic spots) by hydroperoxide, and thereafter the native
      forms (basic spots) were recovered as the acidic forms disappeared.

PMID- 14676402
TI  - Induction of a bystander chromosomal damage of He-ion microbeams in mammalian
      cells.
AB  - We report here a bystander effect in chromosomal damage using He-ion microbeam.
      Human-hamster hybrid cells were irradiated with a precision He-ion microbeam
      generated by the Columbia microbeam system. When 20% of the cells were exposed to
      single He ion, the incidence of cells with chromatid-type breaks detected with
      the PCC technique was covered wide range from 0 to 6 breaks per cell. In
      contrast, the distribution showed a mixed two-peak pattern, such as non-exposed
      and all-cell exposed patterns, under the condition of assuming no bystander
      effect by treating with an effective inhibitor of cell-cell communication. These
      findings provide clear evidence that single He-ion irradiated cells can induce
      bystander chromosomal alterations in neighboring cells not directly hit by He
      ion.

PMID- 14676403
TI  - System of cell irradiation with a precise number of heavy ions (II).
AB  - A single cell irradiation system has been developed at JAERI-Takasaki to
      elucidate biological effects of low dose and low dose-rate space radiation. The
      system has been installed at high-energy collimated heavy-ion microbeam apparatus
      under a vertical beam line of AVF-cyclotron accelerator. Individual mammalian
      cultured cells are irradiated in the atmosphere on the cell dish, the bottom of
      which is made of ion-track-detector TNF-1 (modified CR-39), with a single or
      precise numbers of 11.5 MeV/u 40Ar13+, 13.0 MeV/u 20Ne7+, and 18.3 MeV/u 12C5+
      ions. Positional data of the target cells are obtained at the off-line microscope
      before irradiation. Targeting and irradiation of the cells are performed
      automatically at the on-line microscope of the microbeam apparatus according to
      the obtained data. About 50-100 cells are irradiated in several minutes. The
      number of ions traversed the cells attached on the ion track detector were
      counted with a plastic scintillator-photomultiplier tube assembly and a constant
      fraction discriminator. Immediately after the irradiation, the bottom of the cell
      dish was etched at 37 degrees C to check the spatial distribution of irradiated
      ions. The one batch of cell sample is treated in about 1 hr including the phases
      of cell finding, irradiation, and etching/observing of the ion tracks.

PMID- 14676404
TI  - Effect of gravity stress on fidelity of DNA double-strand break repair.
AB  - DNA double strand break (DSB) causes many cytotoxic effects such as cellular
      lethality, somatic mutation, and carcinogenesis. Fidelity of DSB repair is a
      important factor that determines the quality of genomic stability. It is known
      that the most of DSBs are properly repaired on the earth, however, little is
      known whether those are rejoined at the same fidelity even under the space
      environment. One of the DSB repair pathway, homologous recombination (HR), allows
      the cells to repair their DSBs with error free. Therefore, the efficiency of HR
      is a good index to assess the fidelity of DSB repair. In order to clarify the
      effect of gravity stress on HR pathway, we established a cell line that can
      detect a site-specific DNA repair via HR. The cells carrying a reporter construct
      for HR were incubated under hypergravity condition after induction of site
      specific DSB. Our preliminary results suggest that the gravity stress may affect
      the HR efficiency.

PMID- 14676405
TI  - Indirect influences of radiation on unirradiated cells through irradiated cells.
AB  - There has been a recent upsurge of interest in radiation-induced bystander
      effects. Previously we reported that the accumulation of inducible nitric oxide
      (NO) synthase (iNOS) was induced only in human glioblastoma mutant (m) p53 cells
      by acute irradiation with X-rays, suggesting a suppression of iNOS induction
      after acute irradiation with X-rays in wtp53 cells. NO secreted from the
      irradiated mp53 cells induced the accumulation of p53 in unirradiated wtp53
      cells. The radiosensitivity of wtp53 cells was reduced by exposure to the
      conditioned medium from irradiated mp53 cells, suggesting that NO is an initiator
      of radiation-induced bystander effects. In the present study, we found that the
      accumulation of iNOS in wtp53 cells was induced by chronic irradiation with gamma
      rays followed by acute irradiation with X-rays, but not by each one. It is
      suggested that the accumulation of iNOS may be due to the depression of acute
      irradiation-induced p53 functions by pre-chronic irradiation. We found that
      chronic irradiation with gamma-rays did not inhibit the accumulation of p53 after
      exposure to the conditioned medium from the irradiated mp53 cells. However, the
      decay of accumulated p53 was stimulated by chronic irradiation with gamma-rays.
      At the same time, the accumulation of Hdm2 was observed; suggesting that chronic
      irradiation with gamma-rays may stimulate the degradation of p53 accumulated by
      NO-mediated bystander effects.

PMID- 14676406
TI  - Effect of hypergravity stimulus on XTH gene expression in Arabidopsis thaliana.
AB  - There are several reports indicating that hypergravity and microgravity influence
      the mechanical properties of cell walls in shoots, resulting in changes in the
      growth rate. The mechanical properties of cell walls in dicots are mainly
      determined by the physicochemical properties of xyloglucan, a matrix
      polysaccharide. An increase in the molecular mass of xyloglucan correlated with a
      decrease in cell wall extensibility. Hypergravity is known to increase the
      molecular mass of xyloglucan. The cell wall enzyme, xyloglucan
      endotransglucosylase/hydrolase (XTH) is involved in xyloglucan metabolism. Using
      Arabidopsis, it was examined whether or not the expression of XTH genes in the
      floral stem and rosette leaf is influenced by hypergravity. RT-PCR analysis
      revealed that the expression of XTH genes changes in response to hypergravity of
      300 g.

PMID- 14676407
TI  - Correlation of PP and PR intervals in premature low birth weight infants.
AB  - We examined the developmental change by which autonomic neural activity
      associated respiration modulates spontaneous firing rate of sinus (SA) node and
      atrioventricular (AV) conduction in premature infants born with low birth weight
      (LBWI). The purpose of this study was to clarify whether variation of PR is
      correlated with that of PP or those are independent in LBWI with immature
      autonomic nervous system. We investigated, therefore, whether there are
      spontaneous functional differences in the innervation of SA and AV nodes.
      Further, we evaluated the maturation of autonomic nervous system progressing in
      the period, on the day of birth (Day 0) to approximately one month after the
      birth (Month 1). This study was performed in thirteen LBWI during deep sleep.
      EEG, EOG, ECG, respiratory waves were digitized on line, spontaneous firing cycle
      of SA node (PP), and AV nodal conduction time (PR) that were recorded on Day 0
      and Month 1. Then, the data were analyzed as follows: 1) correlations among the
      means and standard deviations (SD) of PP, PR and RR, 2) variance evaluation of PP
      and PR intervals by Lorenz plot analysis method, 3) correlation analysis among
      PP, PR and RR intervals by linear regression method and 4) frequency analysis for
      PP and PR intervals by high-speed Fourier transform method (FFT) and
      determination of frequency density. The PP interval decreased as growing in the
      period. Contrary PR interval increased. In LBWI, the automatic nervous activities
      including parasympathetic nerve activity for spontaneous firing cycle of SA node
      and ventricular excitation cycle on Month 1 were higher than Day 0. It was
      assumed that the vagal nerve activity for the AV conduction was enhanced.
      However, there was no significant change in linear regression slope for the
      spontaneous firing cycle of SA node and the AV conduction time. Postnatal LF/HF
      changes for PP and PR obtained by frequency analysis, were opposite. Therefore,
      it was suggested that the maturity of autonomic nervous system progresses in the
      period, Day 0 to approximately Month 1, but the variations in PP and PR are
      independent each other.

PMID- 14676408
TI  - Effects of low dose particle radiation to mouse neonatal neurons in culture.
AB  - To investigate effects of low dose heavy particle radiation to CNS system, we
      adopted mouse neonatal brain cells in culture being exposed to heavy ions
      generated by HIMAC at NIRS and BNL. The applied dose varied from 0.05 Gy up to
      2.0 Gy. The subsequent biological effects were evaluated by an induction of
      apoptosis focusing on the dependencies of (1) the animal strains with different
      radiation sensitivities, and (2) LET with different nuclei. Of the three mouse
      strains, SCID, B6 and C3H, used for brain cell culture, SCID was the most
      sensitive and C3H the least sensitive to both X-ray and carbon ion ( 290 MeV/n)
      as evaluated by 10% apoptotic criterion. However, the sensitivity differences
      among the strains were much smaller in case of carbon ion comparing to that of X
      ray. Regarding the LET dependency, the sensitivity was compared with using C3H
      and B6 cells between the carbon (13 keV/micrometers) and neon (70
      keV/micrometers) ions. Carbon (290 MeV/n) did not give a detectable LET
      dependency from the criterion whereas the neon (400 MeV/n) showed 1.4 fold
      difference for both C3H and B6 cells. Although a LET dependency was examined by
      using the most sensitive SCID cells, no significant difference was detected.

PMID- 14676409
TI  - Comparative physiology of postnatal developments of cardiopulmonary reflex.
AB  - We analyzed and compared the frequency components of the heart rate variability
      in human neonate, rat, white chicken, turtle, and frog during the developments.
      Frequency analysis with autocorrelation-FFT method was applied to the heart rate
      and respiration waves to calculate the respiration induced frequency component in
      the power spectra. The comparative analysis of the cardiopulmonary reflex in
      human and rat neonates resulted in a similar developmental progress. In case of
      human immature neonate, respiration induced frequency component in the heart rate
      variability was negligible at day-old 0, and significantly increased at postnatal
      1 month. The rat neonates also showed no or negligible respiration induced
      components until days 8 and it became significant approximately postnatal 1
      month. The white chicken also indicated negligible respiration induced component
      before and a few days after hatching, and became significant after 38 days-old
      (17 days post hatching). However the frog and the turtle indicated no clear
      response in entire periods of the development even in adult. The results strongly
      suggested that gravity may be a possible essential factor of the appearance of
      the post natal development of the cardiopulmonary reflex.

PMID- 14676410
TI  - Seed production of Arabidopsis thaliana under hypobaric conditions.
AB  - In the present study, we examined carbohydrate contents of Arabidopsis thaliana
      seeds during seed development under hypobaric conditions in order to characterize
      the mechanism of low pressure-induced seed damage, and to determine critical
      pressures for seed development under low total and/or low oxygen partial
      pressures. We analyzed contents of starch, sucrose, glucose, and fructose in
      seeds at different developmental stages at 101 kPa total pressure with 21 kPa O2
      partial pressure (control conditions), and at various low pressure conditions (23
      kPa Ptot/21 kPa pO2, 101 kPa Ptot/2 kPa pO2, 53 kPa Ptot/2 kPa pO2, 23 kPa Ptot/2
      kPa pO2, 12 kPa Ptot/10 kPa pO2, and 12 kPa Ptot/2 kPa pO2). Our results indicate
      that maintaining an adequate oxygen partial pressure inside the siliques is
      necessary for seed production under hypobaric conditions.

PMID- 14676411
TI  - DNA microarray analysis of altered gene expression in cadmium-exposed human
      cells.
AB  - Cadmium (Cd) is a heavy metal known to be toxic and carcinogenic, but its
      mechanism of action remains to be elucidated. Development of the DNA microarray
      technology has recently made the comprehensive analysis of gene expression
      possible, and it could be a powerful tool also in toxicological studies. With
      microarray slides containing 7,000-9,000 genes, we have been studying the gene
      expression profiles of a human cell line exposed to Cd. By exposure to a non
      lethal concentration of Cd, 46 upregulated and 10 downregulated genes whose
      expression levels changed twofold or greater were observed. The expression of
      genes related to cellular protection and damage control mechanisms such as those
      encoding metallothioneins, anti-oxidant proteins and heat shock proteins was
      simultaneously induced. In addition, altered expression of many genes involved in
      signaling, metabolism and so on was newly observed. As a whole, a number of genes
      appear to be coordinately regulated toward survival from Cd toxicity. When cells
      were exposed to a higher concentration of Cd, more remarkable effects were
      observed both in the number of affected genes and in the extent of altered
      expression. These findings will contribute to the understanding of the
      complicated biological effects of Cd.

PMID- 14676412
TI  - The new BMI criteria for asians by the regional office for the western pacific
      region of WHO are suitable for screening of overweight to prevent metabolic
      syndrome in elder Japanese workers.
AB  - Obesity occurs less frequently in Japanese than in various other ethnic
      populations. A person with abnormal glucose tolerance is often found to have one
      or more of the other cardiovascular disease risk factors, such as obesity,
      hypertension and hyperlipidemia. This clustering has been labeled as metabolic
      syndrome (WHO, 1998). It was suggested that Japanese, categorized as having
      normal weight (BMI of less than 25.0), as defined by the WHO (2000), have an
      increasing tendency toward metabolic syndrome. Our objective was to analyze
      metabolic syndrome in "Overweight" with BMI of 23.0-24.9 in Japanese workers, and
      to assess the suitability for Asians of the Regional Office for the Western
      Pacific Region of WHO criteria pertaining to obesity (WPRO criteria, 2000). We
      conducted a cross-sectional study in the workplace setting and investigated the
      relationship between BMI classification based on WPRO criteria and metabolic
      syndrome by gender and age group (18-44 yr vs. 45-60 yr). Three hundred seventy
      nine men and 432 women Japanese workers participated in this study. BMI were
      categorized as 20% "Overweight" (23.0-24.9 BMI), 20% "Obese I" (25.0-29.9 BMI)
      and 2% "Obese II" (over 30.0 BMI), based on WPRO criteria. Graded increases in
      BMI were positively associated with body fat percentage, waist circumference, hip
      circumference and waist/hip ratio in both genders and age groups. A progressively
      increasing BMI category in the elder group aged 45-60 yr in both genders was
      positively related with parameters constituting metabolic syndrome. Graded
      increases in BMI classes in elder workers based on WPRO criteria were positively
      associated with prevalence of metabolic syndrome, and "Overweight" elder women
      had significantly higher prevalence of metabolic syndrome. The present
      investigation, based on the increasing risks of "Overweight" with a BMI of 23.0
      24.9, suggests that WPRO criteria are suitable for Japanese workers aged over 45
      yr.

PMID- 14676413
TI  - Persistent insomnia is a predictor of hypertension in Japanese male workers.
AB  - Insomnia is one of the most common complaints at worksites, as well as in the
      general population. This study aims to assess the effect of insomnia on the
      development of hypertension in Japanese male workers. Using the annual health
      examination database of a Japanese telecommunication company, eligible middle
      aged male participants in the 1994 health examination were followed up until 1998
      or the development of hypertension (either initiation of antihypertensive therapy
      or a systolic blood pressure > or = 140 mmHg and/or a diastolic blood pressure >
      or = 90 mmHg). The effect of difficulty initiating sleep (DIS) was assessed with
      a DIS dataset (n=4,794), which included non-DIS (n=4,602) and persistent-DIS
      (n=192) subjects. That of difficulty maintaining sleep (DMS) was assessed with a
      DMS dataset (n=4,443), which included non-DMS (n=4,157) and persistent-DMS
      (n=286) subjects. The incidence of hypertension among persistent-DIS (40.1%;
      130.7 per 1,000 person-yr) was significantly higher than that among non-DIS
      (30.6%; 89.9 per 1,000 person-yr). The incidence of hypertension among persistent
      DMS (42.3%; 136.7 per 1,000 person-yr) was significantly higher than that among
      non-DMS (30.7%; 90.8 per 1,000 person-yr). After adjusting for potential
      confounding factors (i.e. age, body mass index, smoking, alcohol drinking, and
      job stress), persistent complaints of DIS and DMS were significantly associated
      with an increased risk of hypertension (OR=1.96; 95%CI: 1.42-2.70 and OR=1.88;
      95%CI: 1.45-2.45, respectively). Persistent insomnia may be a useful predictor of
      hypertension in Japanese male workers.

PMID- 14676414
TI  - A study on upper extremity cumulative trauma disorder in different unorganised
      sectors of West Bengal, India.
AB  - Cumulative trauma disorder (CTD) is a term used to describe a class of soft
      tissue injuries that result due to a number of occupational activities. These
      disorders commonly occur among workers who are engaged in highly repetitive jobs
      involving continuous hand exertion, vibration and localized mechanical pressure.
      In the present investigation, an attempt was made to evaluate the prevalence of
      CTD among workers associated with strenuous hand intensive jobs in unorganized
      sectors in India and to highlight the unsafe working conditions to which these
      workers have been exposed for several years. For this purpose, an experiment was
      performed on 25 male workers from each group. The groups were classified into
      meat cutters, typists, tailors, visual display terminal (VDT) operators &
      weavers. For the symptom survey, a questionnaire and checklist method was
      implemented. Along with these, a detailed time study was performed among the
      workers during different activities in the total work cycle. For this study a two
      tail chi-square test of independence was applied to determine whether or not the
      feeling of discomfort had any significant association with the repetitiveness of
      the work. From the observations and analysis of the results, it was revealed that
      all the activities are repetitive, i.e. over 50% of the work cycle of each
      activity involved the respective main activity where similar kinds of motion
      patterns were performed. Therefore it can be concluded that high repetitiveness,
      prolonged work activity and remaining in static posture for a prolong period of
      time may be regarded as the causative factors in the occurrence of CTD.

PMID- 14676415
TI  - Sources and assessment of occupational stress in the police.
AB  - The role of the police in Western society is undergoing a transformation that
      reflects the economic social and technological changes in the community and the
      assertion of individual rights within a democracy. The aim of this study is to
      evaluate level of stress among a group of French policemen and to examine the
      association between policing, potential stressors and stress levels. The sample
      is drawn from a large metropolitan police force (n=617). The population extends
      from the first line policeman to top senior management. Each policeman is matched
      for age (more or less five years) and sex, to a control. Policemen and controls
      complete a self administered questionnaire including demographic, occupational
      and health characteristics, and a stress level assessment with the help of a
      visual analogue scale. The average age of the two groups is 40 yr. Eighty-four
      percent are men. The total score for average sources is not statistically
      significantly different for policemen and controls. Comparison of a police group
      with a high stress level to a police population with a low and moderate stress
      level is made. The comparison is done first only with men, and second with the
      whole population. Policemen with a high stress level (same results only for men
      and the whole population) belong to the following groups: more than 15 yr
      service, sergeant, officer and administrative employee rank, divorced experience,
      age over 30, no leisure-time activities and no hobbies. Multivariate analysis
      shows that the two last parameters are bound to the stress level. For the whole
      population, age over 30 has to be added, and for the group of men, length of
      service over five years should be noted. Stress at work is an ill-health
      provoking factor. Police from minority groups such as ageing subjects or police
      officers have been reported to experience greater stress. This population is
      adversely affected by lack of available manpower and long working hours. In fact
      sources of stress in the police population are found both in the weariness of the
      job and private life planning.

PMID- 14676416
TI  - Toxicity due to 2- and 13-wk inhalation exposures of rats and mice to N, N
      dimethylformamide.
AB  - In order to better characterize the toxicity of N,N-dimethylformamide (DMF) and
      to provide its basic toxicity data for risk assessment of workers exposed to DMF,
      F344 rats and BDF1 mice of both sexes were exposed by inhalation (6 h/d x 5 d/wk)
      to 100, 200, 400, 800 or 1,600 ppm DMF for 2 wk, and 50, 100, 200, 400 or 800 ppm
      DMF for 13 wk. Three male and 7 female rats died during the 2-wk exposure to
      1,600 ppm DMF, but no death of the exposed rats or mice occurred under any other
      exposure conditions. Massive, focal and single cell necroses were observed in the
      liver of DMF-exposed rats and mice. The massive necrosis associated with the
      centrilobular fibrosis occurred at the highest exposure concentration. The single
      cell necrosis was associated with fragmentation of the nucleoli as well as an
      increased mitotic figure. The 13-wk exposures of rats and mice to DMF were
      characterized by increases in the relative liver weight and the incidence of the
      centrilobular hepatocellular hypertrophy as well as increased serum levels of
      AST, ALT, LDH, total cholesterol and phospholipid. Lower confidence limits of the
      benchmark dose yielding the response with a 10% extra risk (BMDL10) were
      determined for the relative liver weight and the incidence of hepatocellular
      hypertrophy of the 13-wk exposed animals. The BMDL10 resulted in 1 ppm for the
      increased relative liver weight of male rats and mice and 17 ppm for the
      hepatocellular hypertrophy of male mice.

PMID- 14676417
TI  - Effects of hair dyeing on DNA damage in human lymphocytes.
AB  - Comet assays were carried out to evaluate DNA damage in human lymphocytes from 20
      volunteers before and after hair dyeing. DNA damage in lymphocytes was found to
      be slightly higher in volunteers after hair dyeing. Tail moments before and after
      hair dyeing were 1.47 +/- 0.41 and 1.75 +/- 0.29 respectively (p<0.0008). DNA
      damage in lymphocytes showed significant difference with treatment and heating
      time. The tail moments after 15 min of treatment time before and after hair
      dyeing were 1.44 +/- 0.22 and 1.85 +/- 0.36, respectively (p=0.0004) and the
      corresponding tail moments in 20 min of heating time before and after were 1.37
      +/- 0.15 and 1.78 +/- 0.34 (p=0.0002). In conclusion, we found that an acute
      exposure of hair dyes with heating caused DNA damages in peripheral lymphocytes
      and that this damage had significant association with treatment and heating time.

PMID- 14676418
TI  - Relationships of job and some individual characteristics to occupational injuries
      in employed people: a community-based study.
AB  - This study assessed the associations of job and some individual factors with
      occupational injuries among employed people from a general population in north
      eastern France; 2,562 workers were randomly selected from the working population.
      A mailed auto-questionnaire was filled in by each subject. Statistical analysis
      was performed with loglinear models. The annual incidence rate of at least one
      occupational injury was 4.45%. Significant contributing factors for occupational
      injuries were job category (60.8%), sex (16.2%), regular psychotropic drug use
      (8.5%), age groups (7.5%), and presence of a disease (7.0%). The men had higher
      risk than the women (adjusted odds-ratio 1.99, 95% CI 1.43-2.78). Compared to
      executives, intellectual professionals and teachers, labourers had the highest
      risk (6.40, 3.55-11.52). They were followed by farmers, craftsmen and tradesmen
      (6.18, 2.86-13.08), technicians (3.14, 1.41-6.70), employees (2.94, 1.59-5.48)
      and other subjects (3.87, 1.90-7.88). The young (< or = 29 yr) showed an
      increased risk. Similar odds-ratios were observed for regular psychotropic drug
      use (1.54, 1.16-2.05) and the presence of a disease (1.50, 1.11-2.02). Univariate
      analysis showed that smoking habit, overweight and excess alcohol use were also
      associated with injuries. The loglinear model results showed that there were
      associations between some of these independent factors. It was concluded that
      job, sex, young age, smoking habit, excess alcohol use, overweight, psychotropic
      drug use, and disease influenced the occupational injuries. Preventive measures
      concerning work conditions, risk assessment and job knowledge should be conducted
      in overall active population, especially in men, young workers, smokers, alcohol
      users, overweight workers and in individuals with a disease or psychosomatic
      disorders.

PMID- 14676419
TI  - Relationship between social support, mental health and health care consciousness
      in developing the industrial health education of male employees.
AB  - The purpose of the study is to elucidate the relationship between social support,
      health care consciousness and mental health in developing the industrial health
      education aimed at improving the health habits of male employees. A questionnaire
      survey concerning health practices, mental health based on the General Health
      Questionnaire, social support from social support networks, and health care
      consciousness based on the Health Locus of Control was conducted on male
      employees in three companies in Osaka Prefecture. A total of 1,634 questionnaires
      were collected. Analyses by age group showed that in all age groups, the higher
      the social support score, the more favorable the mental health became and the
      stronger the family care in health care consciousness became. The better the
      mental health, the greater the number of good health practices was and the lower
      the fortune dependence in health care consciousness tended to be. The results of
      the study reconfirm the previous findings that it is necessary to put the mental
      health of male employees in good condition before everything else in effectively
      developing health education aimed at improving their health habits. This study
      also indicates that the level of perception of social support and their internal
      control of self and family in health care consciousness are definitely related to
      the stability of subjects' mental health. It is therefore presumed that measures
      to raise the revel of perception of social support are important since they may
      improve the mental health of subjects.

PMID- 14676420
TI  - A survey on health effects in a human population exposed to permanent-waving
      solution containing thioglycolic acid.
AB  - Thioglycolic acid (TGA) is the active ingredient of permanent-waving solution
      (PWS). TGA has been shown to be a chemical of high toxicity, which can be
      absorbed through intact skin and cause damage to organs or systems in animals.
      This study evaluated the effect of TGA-containing PWS on the health of a human
      population in 3 substudies. Firstly, 57 female hairdressers exposed to TGA
      containing PWS (cases) and 64 female schoolteachers (controls) were studied.
      Their menstruation state was evaluated with information obtained from interviews.
      The results revealed that the menoxenia rate in the cases was significantly
      higher than that in the controls (22.81% vs 9.38%, p<0.05). Secondly, 8 female
      hairdressers selected from those that participated in the above survey underwent
      a fluctuation test for the mutagenic activity of urine. Eight female medical
      students were chosen as controls. Difference in the mutagenic activity of urine
      on TA100 between the two groups was highly significant (110.30 +/- 45.95 vs 28.43
      +/- 19.33, p<0.01). Finally, a micronucleus assay was carried out on scalp hair
      follicle cells in healthy volunteers. Scalp hair with the follicle cell mass was
      sampled from 8 male and 8 female volunteers before permanent waving and at 24, 48
      and 72 h after waving. One thousand hair follicle cells were examined by light
      microscopy. The number of cells containing a micronucleus and the number of
      micronuclei in each cell was determined. The permillages of micronuclei in hair
      follicle cells before and after permanent waving were compared. Micronuclei
      presence reached its peak value (12.44) 24 h after permanent waving, which was
      significantly higher than that before waving (3.13, p<0.001). The rate decreased
      progressively after 24 h. Our results suggest that the reproductive function of
      hairdressers may be affected by long-term exposure to PWS, probably due to the
      presence of TGA, and more attention should be paid to its potential carcinogenic
      effects.

PMID- 14676421
TI  - Pulmonary squamous cyst induced by exposure to indium arsenide in hamsters.

PMID- 14676422
TI  - Micronucleus assay of human lymphocytes: a comparison of cytokinesis-block and
      human capillary blood lymphocytes methods.

PMID- 14676423
TI  - Characterization and distribution of IS8301 in the radioresistant bacterium
      Deinococcus radiodurans.
AB  - The insertion sequence element IS8301 isolated from the radiation resistant
      bacterium Deinococcus radiodurans strain KD8301 was characterized. IS8301 is
      comprised of 1,736-bp, lacks terminal inverted repeats and does not duplicate
      target DNA upon its insertion. The amino acid sequence homology of two open
      reading frames encoded in IS8301 indicates that this insertion sequence element
      belongs to the IS200/IS605 group. There were seven loci completely identical with
      the IS8301 sequence in the published D. radiodurans R(1) genome sequence. The
      genome distribution profiles of IS8301 in strain KD8301 as well as in the three
      different laboratory isolates (KR(1), MR(1), and R(1)) of wild-type D.
      radiodurans were investigated using genomic hybridization analysis. At least 21
      strong hybridization signals were detected in strain KD8301 while only one
      hybridization signal was detected in strain KR(1), the parent strain of KD8301.
      In strain MR1, a different wild-type isolate, six strong hybridization signals
      were detected. In spite of the identification of seven copies of IS8301 in the
      published D. radiodurans R(1) genome sequence, only one hybridization signal was
      detected in strain R(1) purchased from American Type Culture Collection. Using
      inverse PCR and sequencing analyses, total 13 different insertion loci of IS8301
      in the D. radiodurans genome were identified. Sequence comparison of the flanking
      region of insertion sites indicated that the sequence 5'-TTGAT-3' preceded the
      left end of IS8301 in all cases.

PMID- 14676424
TI  - Phylogenetic analyses of Zostera species based on rbcL and matK nucleotide
      sequences: implications for the origin and diversification of seagrasses in
      Japanese waters.
AB  - Seagrasses are composed of four families belonging to angiosperms and they are
      thought to become adaptive to aquatic life independently. Zosteraceae is one such
      family and because of the relatively high species diversity around Japan and
      Korea coast areas, the family might have arisen therefrom. To elucidate the
      origin and evolution of Zosteraceae which consists of three genera, Phyllospadix,
      Zostera, and Heterozostera, 2.8 kb nucleotide sequences of rbcL and matK genes in
      the chloroplast genome were examined for various species, including cosmopolitan
      Z. marina and endemic Z. caulescens. The phylogenetic analysis reveals the
      following three features. First, based on the synonymous nucleotide substitution
      rate of the rice chloroplast genome, we estimated the divergence times between
      Zosteraceae and its closest relative, Potamogetonaceae, and between different
      genera, Zostera and Phyllospadix, as approximately 100 million years (myr) and 36
      myr, respectively, suggesting that Zosteraceae emerged somewhere in the period
      from 36 myr ago to 100 myr ago. Second, two subgenera of Zostera, Zostera and
      Zosterella, exhibit their reciprocal monophyly and appear to have differentiated
      from each other approximately 33 myr ago. However, the third genus Heterozostera
      branched off only 5 myr ago from the stem lineage leading to Zosterella and this
      seems too recent in comparison with the ancient divergence of the two subgenera.
      Third, we estimated the most recent common ancestor of subgenus Zostera as 6 myr.
      In Z. marina four haplotypes were found in the sample and have diversified in the
      past 1.5 myr. One haplotype is shared by both sides of the Japan Archipelago and
      its closely related haplotypes occur also in eastern Pacific Ocean. Based on
      these phylogeographic analyses, we propose a provisional age related
      classification of Zosteraceae to argue the origin and evolution.

PMID- 14676425
TI  - Patterns of codon usage bias in three dicot and four monocot plant species.
AB  - Codon usage in nuclear genes of four monocot and three dicot species was analyzed
      to find general patterns in codon choice of plant species. Codon bias was
      correlated with GC content at the third codon position. GC contents were higher
      in monocot species than in dicot species at all codon positions. The high GC
      contents of monocot species might be the result of relatively strong mutational
      bias that occurred in the lineage of the Poaceae species. In both dicot and
      monocot species, the effective number of codons (ENCs) for most genes was similar
      to that for the expected ENCs based on the GC content at the third codon
      positions. G and C ending codons were detected as the "preferred" codons in
      monocot species, as in Drosophila. Also, many "preferred" codons are the same in
      dicot species. Pyrimidine (C and T) is used more frequently than purine (G and A)
      in four-fold degenerate codon groups.

PMID- 14676426
TI  - Isolation and characterization of two homeodomain leucine zipper genes from the
      dioecious plant Silene latifolia.
AB  - Homeodomain leucine zipper (HD-Zip) genes encode transcription factors that are
      characterized by both a homeodomain and a leucine zipper motif. Two HD-Zip genes
      were isolated from cDNA of the male flower bud of the dioecious plant Silene
      latifolia. The two isolated genes, SlHDL1 and SlHDL2, encode proteins with the
      characteristics of HD-Zip transcription factors belonging to HD-Zip classes I and
      II, respectively. The expression patterns of SlHDL1 and SlHDL2 throughout the
      floral developmental stages were studied using real-time PCR and in situ
      hybridization. SlHDL1 is specifically expressed in the outermost layer of the
      anthers and gynoeciums with a patchy pattern in the inner layers, suggesting that
      the product of SlHDL1 plays a role in the early developmental stage of the
      epidermal tissues of these floral organs. Its expression pattern in the anthers
      and gynoeciums suggests an involvement in differentiation of the reproductive
      organs. On the other hand, real-time PCR revealed accumulation of SlHDL2
      transcripts in the anther and pollen grains of the male flower. These results
      suggest that SlHDL1 and SlHDL2 regulate specific targets in restricted regions
      leading to floral organ differentiation in S. latifolia.

PMID- 14676427
TI  - REC, a new member of the MCM-related protein family, is required for meiotic
      recombination in Drosophila.
AB  - rec mutations result in an extremely low level of recombination and a high
      frequency of primary non-disjunction in the female meiosis of Drosophila
      melanogaster. Here we demonstrate that the rec gene encodes a novel protein
      related to the mini-chromosome maintenance (MCM) proteins. Six MCM proteins (MCM2
      7) are conserved in eukaryotic genomes, and they function as heterohexamers in
      the initiation and progression of mitotic DNA replication. Three rec alleles,
      rec(1), rec(2) and rec (3), were found to possess mutations within this gene, and
      P element-mediated germline transformation with a wild-type rec cDNA fully
      rescued the rec mutant phenotypes. The 885 amino acid REC protein has an MCM
      domain in the middle of its sequence and, like MCM2, 4, 6 and 7, REC contains a
      putative Zn-finger motif. Phylogenetic analyses revealed that REC is distantly
      related to the six conserved MCM proteins. Database searches reveal that there
      are candidates for orthologs of REC in other higher eukaryotes, including human.
      We addressed whether rec is involved in DNA repair in the mitotic division after
      the DNA damage caused by methylmethane sulfonate (MMS) or by X-rays. These
      analyses suggest that the rec gene has no, or only a minor, role in DNA repair
      and recombination in somatic cells.

PMID- 14676428
TI  - The comparison of intrinsic rates of increase among chromosome-substituted lines
      resistant and susceptible to organophosphate insecticides in Drosophila
      melanogaster.
AB  - To investigate the genetic basis of the seasonal fluctuations in resistance to
      three organophosphates, observed within a natural population of Drosophila
      melanogaster (Meigen), we compared the intrinsic rate of increase, generation
      time and net reproduction rate among chromosome substitution lines derived from a
      resistant and a susceptible line, obtained from this natural population. There
      was significant variation among substituted lines; lines possessing the third
      chromosome from the resistant line, which confers resistance to the three
      organophosphates, generally showed lower mean values of these fitness measures.
      Chromosomal analyses also indicated significant negative contributions of the
      third chromosome from the resistant line. However, significant positive
      contributions of the interactions among chromosomes from the resistant line to
      these fitness measures were also detected. We further conducted a local stability
      analysis, in which each chromosome-substituted line was assumed to be introduced
      at a low frequency into the initial susceptible population. It was demonstrated
      that the resistance factor(s) on the third chromosome tend to decrease in their
      frequency under both density-independent and juvenile density-regulated
      conditions. Based on these results, a possible explanation for the seasonal
      fluctuations in resistance to the three organophosphates observed in the natural
      population was proposed.

PMID- 14676429
TI  - Divergence and heterogeneity of the histone gene repeating units in the
      Drosophila melanogaster species subgroup.
AB  - The repeating units of the histone gene cluster containing the H1, H2A, H2B and
      H4 genes were amplified by PCR from the Drosophila melanogaster species subgroup,
      i.e., D. yakuba, D. erecta, D. sechellia, D. mauritiana, D. teissieri and D.
      orena. The PCR products were cloned and their nucleotide sequences of about 4.6
      4.8kbp were determined to elucidate the mechanism of molecular evolution of the
      histone gene family. The heterogeneity among the histone gene repeating units was
      0.6% and 0.7% for D. yakuba and D. sechellia, respectively, indicating the same
      level of heterogeneity as in the H3 gene region of D. melanogaster. Divergence of
      the genes among species even in the most closely related ones was much greater
      than the heterogeneity among family members, indicating a concerted mode of
      evolution for the histone gene repeating units. Among the species in the D.
      melanogaster species subgroup, the histone gene regions as well as 3rd codon
      position of the coding region showed nearly the same GC contents. These results
      suggested that the previous conclusion on analysis of the H3 gene regions, the
      gene family evolution in a concerted fashion, holds true for the whole histone
      gene repeating unit.

PMID- 14676430
TI  - Marker chromosomes in Korean patients: incidence, identification and diagnostic
      approach.
AB  - The identification of marker chromosomes is important for genetic counseling.
      However, the origin or composition can rarely be defined with conventional
      cytogenetic technique alone. In this study, we investigated the incidences and
      types of marker chromosomes in Korean patients and attempted to establish a cost
      effective diagnostic approach for marker chromosomes. We reviewed the karyotypes
      of 2,984 patients that were requested for the cytogenetic analysis between 1997
      and 2003 at the Samsung Medical Center. Ten marker chromosomes were found and
      identified using fluorescent in situ hybridization (FISH). Among the ten marker
      chromosomes, six were supernumerary marker chromosomes (SMCs) and the rest were
      marker chromosomes in Turner syndrome (TS). The incidence of SMCs was 2.01/1,000,
      slightly higher than that previously reported. Five of six SMCs were satellited
      marker chromosomes. Three bisatellited marker chromosomes originated from
      chromosome 15 and two from chromosome 22. The origin of one SMC could not be
      identified. All marker chromosomes in TS originated from X- or Y chromosome. The
      application of FISH is indispensable to identify marker chromosomes, and the
      appropriate selection of probes is necessary for cost-effective analysis. For
      analyzing satellited marker chromosomes, application of probes for chromosome 15
      followed by those for chromosome 22 is recommended and in cases of TS, probes for
      sex chromosomes should take precedence.

PMID- 14676431
TI  - Comparison of mortality and morbidity in multiple versus singleton very low birth
      weight infants in a neonatal intensive care unit.
AB  - Multiple births in Korea have been increased recently as a consequence of
      increased infertility due to advancing maternal age at first birth, and increased
      use of assisted reproductive technology. Multiples suffer higher mortality and
      morbidity than singletons. However, it is not clear whether preterm multiple very
      low birth weight infants (VLBWI) suffer higher mortality and morbidity than
      comparable singletons. We evaluated 266 singleton and 113 multiple VLBWI to
      determine whether mortality and morbidity in multiple VLBWI were higher than
      those in comparable singletons. The rate of in vitro fertilization and cesarean
      section were significantly higher in multiples than singletons. The total and the
      adjusted mortality with gestational age and birth weight were not significantly
      different between the two groups. Maternal age and the incidence of respiratory
      distress syndrome, patent ductus arteriosus, bronchopulmonary dysplasia,
      intracranial hemorrhage (grade> or =3), cystic periventricular leukomalacia, and
      retinopathy of prematurity (stage> or =3) were not significantly different
      between the two groups, and the incidence of abnormal brainstem auditory evoked
      potential was higher among the singletons. These results suggest that multiple
      VLBWI do not suffer higher mortality or morbidity than comparable singletons.

PMID- 14676432
TI  - Attitudes and reported practices of Korean primary care physicians for health
      promotion.
AB  - To examine attitudes and practice patterns of primary care physicians in health
      promotion and to probe factors associated with active involvement, a nationwide
      cross-sectional postal questionnaire survey of randomly sampled Korean family
      physicians and internists was performed. The areas of health promotion examined
      were; smoking, alcohol consumption, stress, exercise, and diet. Overall response
      rate was 38.0% and an interview survey of sub-samples of non-responders found no
      differences in socio-demographic characteristics or survey results versus
      original responders, except for the rate of collecting information on smoking and
      diet. Smoking cessation was considered important by 92% of responders, while
      other lifestyle factors were considered important by less than 70%. Approximately
      80% of responders believed in effectiveness of lifestyle counseling, except for
      stress. The frequency of collecting information, providing counseling, and the
      level of preparedness to undertake counseling were higher for smoking and alcohol
      than for other factors. Beliefs in effectiveness of health promotion and
      preparedness to undertake counseling were positively associated with frequency of
      information collection and providing counseling, even after adjusting for socio
      demographic factors. Efforts should be made to change the physicians perception
      of effectiveness and importance of health promotion, and to improve physician's
      preparedness to actively intervene.

PMID- 14676433
TI  - The origin of proinflammatory cytokines in patients with idiopathic dilated
      cardiomyopathy.
AB  - Proinflammatory cytokines and their receptors are increased in the peripheral
      blood of patients with heart failure. We measured cytokines and their receptors
      in systemic artery (SA), coronary sinus (CS) and infra-renal inferior vena cava
      (IVC), in order to investigate their origin and influential factors. Thirty
      patients with idiopathic dilated cardiomyopathy were performed echocardiography
      at admission, and right heart catheterization after stabilization. Blood was
      drawn from 3 sites for measurement of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6) and soluble tumor necrosis factor-alpha receptor (sTNFR) I,
      II. TNF-alpha at CS (3.25 +/- 0.34 pg/mL) was higher than those of SA (1.81 +/-
      0.39 pg/mL) and IVC (1.88 +/- 0.38 pg/mL, p<0.05). IL-6 at CS (18.3 +/- 3.8
      pg/mL) was higher than that of SA (5.8 +/- 1.2 pg/mL, p<0.01). The levels of
      sTNFR I, II showed increasing tendency in sequence of SA, IVC and CS. TNF-alpha
      and sTNFR I, II from all sites were proportional to worsening of functional
      classes at admission (p<0.05). E/Ea by Doppler study at admission, which reflects
      left ventricular end-diastolic pressure (LVEDP) was positively correlated with
      TNF-alpha from SA (R=0.71, p<0.01), CS (R=0.52, p<0.05) and IVC (R=0.46, p<0.05).
      Thus, elevated LVEDP during decompensation might cause cytokine release from
      myocardium in patients with idiopathic dilated cardiomyopathy.

PMID- 14676434
TI  - Intramyocardial transplantation of circulating CD34+ cells: source of stem cells
      for myocardial regeneration.
AB  - This study was designed to investigate the increase in the number of circulating
      CD34+ cells after acute myocardial infarction (MI) and the differentiation of
      these cells to cardiomyocytes after transplantation into infarcted myocardium.
      The study involved five donor groups: MI (n=27), sham (n=26), granulocyte-colony
      stimulating factor (GCSF) (n=26), MI+GCSF (n=25), and control (n=25). Acute MI
      was induced by ligating the left anterior descending coronary arteries (LAD) of
      donor rats, and LAD of recipient rats were ligated on the same day. Seven days
      after ligation, CD34+ cells in donor rats were counted and then were directly
      injected into the infarcted myocardium of recipient rats. Eight weeks after the
      transplantation, significant differences (p<0.001) were observed in the CD34+cell
      counts among the 5 donor groups with the greatest increase in the MI+GCSF donor
      group. In rats receiving CD34+ cells, the size of the scar area smaller (p<0.001)
      and the thickness of the scar was greater (p=0.001) than in CD34- and saline
      transplanted rats. The transplanted CD34+ cells differentiated into
      cardiomyocytes in the scar. This study suggests that CD34+ cells may be a
      potential source of stem cells and that they may be useful in strategies aimed at
      the regeneration of infarcted myocardium.

PMID- 14676435
TI  - Pax5 expression in non-Hodgkin's lymphomas and acute leukemias.
AB  - The Pax5 gene encodes the B-cell-specific activator protein which is a key
      regulator in development and differentiation of B-cell. We studied the expression
      of Pax5 in hematologic malignancies to evaluate the diagnostic utility as a B
      cell marker. Materials included 70 B cell lymphomas, 26 T cell lymphomas, 53
      acute leukemias, and 6 multiple myelomas (MMs). Representative areas from the
      paraffin embedded tissues were selected for tissue microarray, and the
      expressions of Pax5 was immunohistochemically evaluated. Pax5 was strongly
      expressed in most of the B cell lymphomas; 44 of 47 diffuse large B cell
      lymphomas (93.6%), 15 of 16 marginal zone B cell lymphomas (93.8%), all 3 mantle
      cell lymphomas, 2 follicular lymphomas, and 2 Burkitt's lymphomas (100%).
      However, Pax5 was expressed in only one of 26 T cell lymphomas. Among leukemias,
      it was expressed in 10 of the 14 B acute lymphocytic leukemias (ALLs) (72.4%),
      but also in 3 of the 6 T ALLs (50%), 13 of the 26 acute myelogenous leukemias
      (AMLs) (50%) and in all 3 ALL arising in chronic myelogenous leukemias and 4
      mixed B ALL and AML. In MMs, Pax5 was negative in all cases. We concluded that
      Pax5 is very useful B cell marker in classification of lymphomas, but not of
      acute leukemias.

PMID- 14676436
TI  - Exposure to toluene diisocyanate (TDI) induces IL-8 production from bronchial
      epithelial cells: effect of pro-inflammatory cytokines.
AB  - This investigation was designed to confirm IL-8 production from human bronchial
      epithelial cells with toluene diisocyanate (TDI) exposure and to examine the
      effects of pro-inflammatory cytokine and dexamethasone. We cultured Beas-2B, a
      bronchial epithelial cell line with TDI-HSA conjugate and compared with those
      without conjugate. IL-8 in the supernatant was measured by ELISA. To evaluate the
      effect of proinflammatory cytokines, peripheral blood mononuclear cells (PBMC)
      were collected from TDI- and non-TDI asthma patients, and were added to the
      epithelial cell culture. Dexamethasone or antibodies to TNF-alpha and IL-1beta
      were pre-incubated with PBMC supernatant. There was a significant production of
      IL-8 from bronchial epithelial cells with addition of TDI-HSA conjugate in a dose
      dependent manner, which was significantly augmented with addition of PBMC
      supernatant. Higher production of IL-8 was noted with addition of PBMC
      supernatant from TDI-asthma patients than in those from non-TDI asthma patients.
      IL-1beta and IL-1beta/TNF alpha antibodies were able to suppress the IL-8
      productions. Pre-treatment of dexamethasone induced dose-dependent inhibition of
      the IL-8 production. These results suggest that the IL-8 production from
      bronchial epithelial cells contribute to neutrophil recruitment occurring in TDI
      induced airway inflammation. IL-1beta released from PBMC of TDI-induced asthma
      patients may be one of the pro-inflammatory cytokines to enhance IL-8 production.

PMID- 14676437
TI  - Combined effect of low-dose nitric oxide gas inhalation with partial liquid
      ventilation on hemodynamics, pulmonary function, and gas exchange in acute lung
      injury of newborn piglets.
AB  - We conducted a randomized animal study to determine whether there is a cumulative
      effect on hemodynamics, pulmonary function, and gas exchange when low-dose nitric
      oxide (NO) is added to partial liquid ventilation (PLV) in acute lung injury.
      Eighteen newborn piglets were saline-lavaged repeatedly, and randomly divided
      into two groups: PLV with perfluorocarbon group (n=8) and lavage only (control)
      group (n=10). Perfluorodecalin (30 mL/kg) was instilled into the endotracheal
      tube for 30 min, followed by 5-10 mL/kg/hr. Fifteen minutes after the completion
      of perfluorodecalin dosing, NO (10 ppm) was added to the inspiratory gas in an
      "on/off" manner. Perfluorodecalin instillation produced a significant improvement
      in gas exchange, pulmonary mechanics, shunt, and pulmonary arterial pressure
      (PAP). The addition of NO produced a further significant improvement in PaO2 and
      PAP. The "on/off" response to NO was seen apparently in PAP, PaO2, dynamic
      compliance, and shunt. All the variables in control group were remained at near
      the after-lavage levels without significant improvements until the end of the
      experiment. We concluded that NO might have a cumulative effect on gas exchange
      when combined with PLV, and this might be attributable to deceased PAP and V/Q
      mismatching.

PMID- 14676438
TI  - Lung matrix metalloproteinase-9 correlates with cigarette smoking and obstruction
      of airflow.
AB  - Cigarette smoking is the most important risk factor for obstruction of airflow in
      chronic obstructive pulmonary disease (COPD). Matrix metalloproteinases (MMPs) or
      an imbalance between MMPs and their inhibitors, the tissue inhibitors of MMP
      (TIMPs), is considered to play a role in the pathogenesis of COPD. We
      investigated whether the MMPs expression or the imbalance between MMPs and TIMP-1
      is associated with the amount of cigarette smoking and the FEV1 value, in the
      lung parenchyma of 26 subjects (6 non-smokers and 20 cigarette smokers). First,
      we performed zymographic analysis to identify the profile of the MMPs, which
      revealed gelatinolytic bands mainly equivalent to MMP-9 in the smokers. We then
      measured, using enzyme immunoassay, the concentrations of MMP-9 and its
      inhibitor, TIMP-1. Correlation analysis revealed that both the MMP-9
      concentrations and the molar ratios of MMP-9 to TIMP-1 (MMP-9/TIMP-1) were
      correlated with the amount of cigarette smoking. Furthermore, MMP-9
      concentrations were inversely correlated with FEV1. In conclusion, this study
      shows that MMP-9 expression in human lung parenchyma is associated with cigarette
      smoking and also with the obstruction of airflow, suggesting that MMP-9 may play
      a role in the pathogenesis of the cigarette smoke-induced obstruction of airflow
      known as the characteristic of COPD.

PMID- 14676439
TI  - Hypoplasia of the left portal vein territory of the human liver: a case study.
AB  - Although reports of hypoplasia or absence of the liver of left lobe are not few,
      descriptions of the intrahepatic vessels are rare but valuable for discussion of
      the pathogenesis. The present report demonstrates a case of the left surgical
      lobe hypoplasia that is characterized by 1) the scar-like lobe with few
      parenchymal tissue and dilated bile ducts, 2) no Spiegel's lobe with the portal
      vein stuck to the inferior vena cava, 3) unusual configurations of the right
      hepatic vein and the 8th segmental portal vein branch, 4) the hepatic groove on
      S8, and 5) the trifurcation pattern of the portal vein primary division.
      According to the macroscopic and histological observations, we hypothesized that
      the secondary abnormal peritoneal fusion occurred in utero and/or during the
      postnatal growth, and that it involved the left portal vein and other adjacent
      structures, resulting in severe atrophy of the left surgical lobe.

PMID- 14676440
TI  - The prognosis of liver cirrhosis in recent years in Korea.
AB  - The survival of a recent series of 823 cirrhosis patients who were followed up
      for a mean of 48 months was analyzed. Cirrhosis was ascribed to alcohol (26%),
      hepatitis virus B (58%), hepatitis virus C (11%) or both (2%), or was cryptogenic
      (3%). Features of decompensation were observed in 51% of the patients at entry,
      and newly developed in 44% of compensated patients within 5 yr. The 5-yr survival
      after decompensation was 25%. The leading causes of death were liver failure
      (53%), hepatocellular carcinoma (HCC, 23%), and variceal bleeding (10%). Early
      detection of HCC significantly improved the survival of cirrhosis patients.
      Biannual ultrasonography increased the detection rate of small HCC. Mortality of
      variceal hemorrhage was much lower in patients with Child-Pugh scores from 5 to 8
      than in those with scores above 8 (5% vs. 52%). Endoscopic prophylaxis
      significantly decreased the incidence of first variceal hemorrhage, but the
      effect was insufficient to improve the rate of survival. Mortality of first
      spontaneous bacterial peritonitis was 18%. These data suggest that the mortality
      of major complications of liver cirrhosis has considerably decreased during the
      last two decades, while there was no remarkable improvement in long-term
      survival. More efficient management of etiologic factors would be required.

PMID- 14676441
TI  - Hepatocyte expressions in hepatocellular carcinomas, gastrointestinal neoplasms,
      and non-neoplastic gastrointestinal mucosa: its role as a diagnostic marker.
AB  - We performed immunohistochemical staining against Hepatocyte (Hep) and CD10
      antibodies in 75 hepatocellular carcinoma (HCC), 50 cholangiocarcinomas, 49
      colorectal adenocarcinomas, and 308 gastric adenocarcinomas by tissue array
      method. We also evaluated the various non-neoplastic adult tissues and fetal
      digestive organs. Hep was expressed in 80% of HCCs, and HCCs without Hep
      expression were more likely to have a higher Edmondson & Steiner grade than HCCs
      with Hep expression (p=0.004). In non-HCCs, 16% of cholangiocarcinomas, 8.2% of
      colorectal carcinomas, and 44.2% of gastric carcinomas expressed Hep. Gastric
      carcinomas with Hep expression were significantly associated with early gastric
      carcinomas (p<0.001). In non-neoplastic tissues, Hep was found expressed in
      normal hepatocytes, small intestinal mucosa, and intestinal metaplasia of the
      stomach. Fetal hepatocytes expressed Hep after 19 weeks of gestation. CD10 was
      detected in 46.7% (35/75) of HCCs, and canalicular staining pattern was
      predominant in HCCs. In conclusion, the expression of Hep and CD10 may help to
      distinguish HCCs from non-HCCs.

PMID- 14676442
TI  - The prophylactic use of lamivudine can maintain dose-intensity of adriamycin in
      hepatitis-B surface antigen (HBs Ag)-positive patients with Non-Hodgkin's
      lymphoma who receive cytotoxic chemotherapy.
AB  - We investigated the effectiveness of lamivudine to prevent hepatitis flare up due
      to reactivation of hepatitis-B virus (HBV) in hepatitis-B surface antigen (HBsAg)
      positive patients with Non-Hodgkin's lymphoma (NHL) during cytotoxic
      chemotherapy. HBsAg-positive patients with NHL were identified from the lymphoma
      database of the Asan Medical Center from January 1995 to August 2002, and their
      medical records were reviewed. We found that 31 patients were received cytotoxic
      chemotherapy among 41 NHL patients with HBsAg-positive during same period. We
      divided them into 2 groups of HBsAg patients with NHL as follows: Group A who
      received cytotoxic chemotherapy with lamivudine 100 mg daily; Group B without any
      prophylactic antiviral therapy. There were no significant differences between
      Group A and B in several clinical variables. Seventeen patients (85%) in group B
      and one patient (9%) in Group A had hepatitis due to reactivation of HBV
      (p<0.001), with one hepatic failure related death in Group B and none in group A.
      The mean dose intensity of adriamycin actually delivered was 13.3 mg/m2/week (80%
      Relative Dose intensity (RDI)) in Group A and 9.1 mg/m2/week (55% RDI) in Groups
      B (p<0.001). Our data suggest that the frequency of chemotherapy-related HBV
      reactivation may be significantly decreased by lamivudine prophylaxis with
      maintenance of the dosage of adriamycin.

PMID- 14676443
TI  - The role of bile carcinoembryonic antigen in diagnosing bile duct cancer.
AB  - It is known that the fluids bathing tumors might contain a higher level of the
      carcinoembryonic antigen (CEA) than those found in the blood. Therefore, we
      evaluated the role of bile CEA in diagnosing bile duct cancer. One hundred and
      thirty two patients were prospectively studied. The patients were divided into 3
      groups: the bile duct cancer (n=32), pancreatic cancer (n=16), and benign biliary
      diseases (n=84) groups. Bile samples were obtained on the next day of the biliary
      drainage procedures. The mean bile CEA level in those with bile duct cancer
      (120.6 +/- 156.9 ng/mL) was significantly higher than those with pancreatic
      cancer and benign biliary diseases (32.0 +/- 28.5 ng/mL, 29.3 +/- 56.3 ng/mL).
      Using the level of 20 ng/mL, the sensitivity and specificity of bile CEA in the
      diagnosis of bile duct cancer from benign biliary diseases were 65.6% and 66.7%,
      respectively. Both the bile CEA and total bilirubin level were found to be an
      independent factor linked to bile duct cancer. This study result suggests that
      bile CEA level is a useful supplementary test for diagnosing bile duct cancer.

PMID- 14676444
TI  - Clinical characteristics and outcome of hydronephrosis detected by prenatal
      ultrasonography.
AB  - The widespread use of prenatal ultrasound results in an increased recognition of
      fetal hydronephrosis. To determine clinical characteristics and postnatal outcome
      of fetal hydronephrosis, we performed a retrospective study in children diagnosed
      as having fetal hydronephrosis between 1990 and 2001. 341 children with 427
      dilated kidneys were included. Dilatation of the renal pelvis was caused by
      primary ureteropelvic junction obstruction in 65.6%, multicystic kidney in 9.4%,
      vesicoureteral reflux in 7.0%, duplex system in 5.4%, ureterovesical junction
      obstruction in 4.0%, and posterior urethral valves in 3.0%. Hydronephrosis
      resolved spontaneously in 126 (29.5%) kidneys, with 52.7% of mild hydronephrosis,
      and 2.6% of severe hydronephrosis. Mean interval to spontaneous resolution was
      1.39 (+/- 1.41, SD) yr. Surgery was performed in 174 kidneys, including
      pyeloplasty in 105, ureteroneocystostomy in 23, transurethral incision in 11 and
      nephrectomy in 9. Most patients had initially high-grade hydronephrosis (p<0.05).
      Mild hydronephrosis appears to be relatively benign, and in most cases,
      dilatation improves with time, and thus surgical intervention is not required. On
      the other hand, moderate or severe hydronephrosis often results in a
      significantly poor outcome and requires surgical intervention, and therefore,
      requires closer follow-up both antenatally and postnatally.

PMID- 14676445
TI  - Preoperative anxiety and propofol requirement in conscious sedation for ovum
      retrieval.
AB  - The purpose of the present study was to evaluate the correlation among the trial
      number of in vitro fertilization (IVF), preoperative anxiety, and propofol
      requirement for conscious sedation. One hundred and twenty six Korean women
      undergoing oocyte retrieval were enrolled. The target-controlled infusion by the
      anesthesiologist was conducted with initial target propofol concentration of 2.5
      microg/mL, which was manipulated until the sedation score 3 and desired clinical
      end point were achieved. A weak correlation was observed between visual analogue
      scale (VAS) anxiety and the dose of propofol required for the induction of
      conscious sedation (r=0.22, p=0.0192). A weak correlation was also found between
      VAS anxiety and the sedation time needed to reach the proper conscious sedation
      level for the procedure (r=0.181, p=0.0484). Multiple regression analysis showed
      that VAS anxiety, preoperative baseline prolactin level, and cortisol level had
      statistically significant effects on the propofol induction dose for target
      controlled conscious sedation. We concluded that the induction dose and time
      requirements for propofol in anesthesiologist-controlled conscious sedation be
      modified based on the preoperative anxiety level and the baseline blood
      concentration of stress hormone, cortisol and prolactin.

PMID- 14676446
TI  - Effects of dopamine infusion on cerebral blood flow, brain cell membrane function
      and energy metabolism in experimental Escherichia coli meningitis in the newborn
      piglet.
AB  - In the present study, we tested whether maintenance of adequate cerebral
      perfusion pressure (CPP) by pharmacologically preventing systemic hypotension
      with dopamine infusion would prevent cerebral ischemia and attenuate energy
      depletion and neuronal injury even though intracranial pressure remains elevated
      in a newborn piglet meningitis model. Cerebral blood flow, measured at the end of
      the experiment using fluorescent microspheres, was significantly increased by
      dopamine infusion. The decreased cerebral cortical cell membrane Na+, K+ -ATPase
      activity and increased lipid peroxidation products, indicative of meningitis
      induced brain damage, were significantly attenuated by dopamine infusion.
      Dopamine also significantly attenuated the meningitis-induced reduction in both
      brain ATP and phosphocreatine levels and the increase in brain lactate level. In
      summary, maintenance of adequate CPP with dopamine prevented cerebral ischemia,
      reduced cerebral energy depletion, and attenuated brain injury in neonatal
      bacterial meningitis.

PMID- 14676447
TI  - Associations of Moyamoya patients with HLA class I and class II alleles in the
      Korean population.
AB  - Moyamoya disease is characterized by progressive cerebrovascular occlusion at the
      peripheral internal carotid artery and development of abnormal collateral
      circulation at the cerebral basal region. Although abnormal thrombogenesis,
      inflammation and autoimmune process might be involved in the etiology, the
      genetic pathogenesis of Moyamoya disease is still unknown. To evaluate the
      association of Moyamoya disease with HLA alleles in the Korean population, we
      investigated HLA class I and class II alleles in 28 Moyamoya patients and 198
      unrelated healthy controls. The frequency of HLA-B35 allele was significantly
      increased in the patients compared to the controls (32.1% vs. 10.1%, RR=4.2,
      p<0.008). Further analysis of HLA-B35 on onset age and sex showed that this
      allele was significantly increased compared to the controls in both late-onset
      and female group. Especially, HLA-B35 was the most significantly increased in
      female of late-onset group compared to the controls. These results suggest that
      HLA-B35 may be an useful genetic marker for Moyamoya disease, and particularly in
      females of late onset group in the Korean population.

PMID- 14676448
TI  - Orbital trapdoor fracture in children.
AB  - This study was performed to evaluate the clinical symptom, fracture finding, and
      surgical outcome in children with orbital trapdoor fracture. Forty-four patients
      with pure orbital trapdoor fracture, under 18 yr of age, were included. Time
      interval between injury and surgery, length of time for improvement, resolution
      of ocular motility restriction, and other factors were analyzed in 36 patients
      who underwent surgery. The median improvement time was 3.5 days for patients
      (n=8) receiving surgery within 5 days, 18.0 for those (n=19) receiving surgery
      between 6 and 14 days, and 50.0 for those (n=9) receiving surgery after 15 days
      (p=0.03). One month after operation, the mean change in supraduction limitation
      was 3.50 +/- 0.53 for patients receiving surgery within 5 days, 2.11 +/- 1.24 for
      those receiving surgery between 6 and 14 days, and 1.67 +/- 0.82 for those
      receiving surgery after 15 days (p=0.04). Three months after operation, the mean
      change in supraduction limitation was 3.88 +/- 0.35, 2.94 +/- 1.55, and 2.50 +/-
      1.38, respectively (p=0.14). In conclusion, trapdoor fracture of the orbit in
      children must be diagnosed by careful CT evaluation and clinical evidence of
      entrapment. For patients with severe limitation of ocular motility, early surgery
      within 5 days of injury leads to more rapid and better postoperative improvement.

PMID- 14676449
TI  - Two cases of anaphylaxis after laminaria insertion.
AB  - Anaphylaxis following laminaria insertion rarely occurs but may be a life
      threatening condition. Laminaria tents, prepared from natural sea kelp, are
      commonly used prior to elective termination of pregnancy to achieve cervical
      dilatation. We report herein two cases of anaphylaxis caused by IgE-mediated
      hypersensitivity to laminaria. Two women, each of whom had undergone at least one
      previous abortion where a laminaria had been utilized, developed anaphylactic
      reaction following laminaria insertion. The reaction included urticaria, nausea,
      breathing difficulty, and hypotension. The patients subsequently underwent skin
      testing and measurement of serum specific IgE level to laminaria extract, and
      were shown to elicit positive responses to laminaria. The implication and impact
      of laminaria allergy on gynecologic procedures are significant and this allergy
      should be included in the list of differential diagnoses for hypersensitive
      reaction in gynecologic procedures.

PMID- 14676450
TI  - A case of acute myocardial infarction after blunt chest trauma in a young man.
AB  - Coronary artery injury rarely occurs after blunt chest trauma, but it can lead to
      extensive myocardial infarction and be frequently overlooked. A 16-yr-old man was
      presented with comatose mental state and rapid respiration rate. He ran into
      guard rail while riding a motorcycle. In routine examination, his
      electrocardiogram showed Q wave and 2 mm ST segment elevation in all precordial
      leads, I and aVL. The cardiac enzymes were also elevated: creatine kinase (CK)-MB
      was 300 U/L, and cardiac specific troponin I was 5.7 ng/mL. Two-dimensional
      echocardiography showed anteroseptal akinesia with severely depressed left
      ventricular function, ejection fraction of 28%. He could not receive any
      anticoagulation or thrombolytic therapy because of his brain lesion. Three weeks
      later, his mental state improved. A diagnostic coronary angiogram revealed total
      occlusion in the proximal left anterior descending artery (LAD) with collaterals
      from the right coronary artery and left circumflex artery. We successfully
      performed a percutaneous coronary intervention for the LAD lesion, and the final
      angiogram showed a good coronary flow without residual stenosis.

PMID- 14676451
TI  - Acute hemolytic transfusion reactions due to multiple alloantibodies including
      anti-E, anti-c and anti-Jkb.
AB  - We report a case of two consecutive episodes of acute hemolytic transfusion
      reactions (HTRs) due to multiple alloantibodies in a 34-yr-old man who suffered
      from avascular necrosis of left femoral head. He received five units of packed
      red blood cells (RBCs) during surgery. Then the transfusion of packed RBCs was
      required nine days after the surgery because of the unexplained drop in
      hemoglobin level. The transfusion of the first two units resulted in fever and
      brown-colored urine, but he received the transfusion of another packed RBCs the
      next day. He experienced even more severe symptoms during the transfusion of the
      first unit. We performed antibody screening test, and it showed positive results.
      Multiple alloantibodies including anti-E, anti-c and anti-Jkb were detected by
      antibody identification study. Acute HTRs due to multiple alloantibodies were
      diagnosed, and the supportive cares were done for 6 days. We suggest the antibody
      screening test should be included in the panel of pretransfusion tests for safer
      transfusion, and it is particularly mandatory for the patients with multiple
      transfusions, pregnant women, and preoperative patients.

PMID- 14676453
TI  - Membranous glomerulopathy as a manifestation of chronic graft-versus-host-disease
      after non-myeloablative stem cell transplantation in a patient with paroxysmal
      nocturnal hemoglobinuria.
AB  - Allogeneic stem cell transplantation (allo-SCT) using related or unrelated donor
      could eradicate paroxysmal nocturnal hemoglobinuria (PNH) clones and may cure the
      disease. Chronic graft-versus host disease (GVHD) is a major complication of
      patients who have undergone allo-SCT. Nephrotic syndrome has been described as
      one of the rare manifestations of chronic GVHD following the usual myeloablative
      allo-SCT. We report a case of nephrotic syndrome that developed 25 months after
      non-myeloablative allo-SCT for PNH. The patient had grade II acute GVHD and
      extensive chronic GVHD after non-myeloablative allo-SCT. Typically the patient
      presented with preserved renal function and full nephrotic syndrome including
      generalized edema, proteinuria, hypoalbuminemia, and hypercholesterolemia. Renal
      biopsy revealed findings of membranous glomerulopathy (MG). The patient is alive
      with a stable engraftment and full donor chimerism under the administration of
      tacrolimus for control of chronic GVHD and MG without refractory hemolysis and
      cytopenia.

PMID- 14676452
TI  - Primary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid
      tissue-type in the thymus of a patient with Sjogren's syndrome and rheumatoid
      arthritis.
AB  - Primary thymic marginal zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid
      tissue (MALT)-type is a very rare disease with distinct clinicopathologic
      features. I herein report a rare case of primary thymic MZBL of MALT-type arising
      in the thymus in a patient with Sjogren's syndrome and rheumatoid arthritis. A
      mediastinal mass was detected by computerized tomography in a 43-yr-old Korean
      woman with a history of Sjogren's syndrome and rheumatoid arthritis and the
      thymus was resected through median sternotomy. The solid and nodular tumor (7x6x3
      cm) was confined in the thymus. Histologically, the lymphoid infiltrate comprised
      monotonous centrocyte-like cells with monocytoid cells, small lymphocytes, and
      plasma cells. Prominent lymphoepithelial lesions were formed by centrocyte-like
      cells infiltrating the Hassall's corpuscles. Immunohistochemically, the tumor
      cells were positive for CD20, CD79a, and bcl-2 and negative for CD3, CD5, CD10,
      CD23, and bcl-6. IgA and kappa light chain restriction were also found in plasma
      cells in the tumor. Sjogren's syndrome and rheumatoid arthritis are known to be
      associated with MALT lymphoma and were considered to play an important role in
      the development of malignant lymphoma in this patient.

PMID- 14676454
TI  - Ovarian mature cystic teratoma containing homunculus: a case report.
AB  - We report a partial fetus-like structure (homunculus) in benign ovarian mature
      cystic teratoma removed from a 23-yr-old female. The cyst displayed various
      tissues derived from the three germ layers. The homunculus had a distinguished
      fetal cranial structure with one upper extremity. A partially developed
      osteocartilagenous skeleton was identified in the cranial structure of the
      homunculus. Intracranial structures such as cerebral cortex, retinal pigment, and
      leptomeninges were extruded from the partially disrupted calvarium.

PMID- 14676455
TI  - A case of coexistent angiosarcoma and follicular carcinoma of the thyroid.
AB  - Angiosarcoma of the thyroid has long been a controversial entity, and it is
      histologically defined as cleft-like anastosmosing spaces lined by large,
      atypical cells of endothelial lineage. However, clear-cut separation between the
      angiosarcoma and anaplastic carcinoma of the thyroid is difficult because they
      yield nearly the same clinical prognosis and overlapping histologic findings. We
      report a case of thyroid neoplasm composed of minimally invasive well
      differentiated follicular carcinoma and angiosarcoma with intervening
      transitional area. Immunohistochemically, the angiosarcomatous portion showed
      focal immunoreactivity for endothelial markers such as CD31, CD34, Ulex europaeus
      1 lectin, factor VIII-related antigen, and immunonegativity for epithelial
      markers including pancytokeratin, epithelial membrane antigen and thyroglobulin,
      whereas the reverse was demonstrated in the minimally invasive follicular
      carcinomatous portion. The follicular carcinoma portion was positive for thyroid
      transcription factor-1 (TTF-1). Each component showed ultrastructural findings of
      epithelial and endothelial differentiation, respectively. The present case was
      unique in that angiosarcoma of the thyroid was confirmed by immunohistochemistry
      and electron microscopy, as well as light microscopy, and also coexisted with a
      minimally invasive well differentiated follicular carcinoma in the same mass.
      This combination has never been described in the literature. Although restricted
      to a single case, the present case further supports that angiosarcoma is a true
      existent entity rather than a variant of anaplastic carcinoma.

PMID- 14676456
TI  - Synchronous bony and soft tissue metastases from follicular carcinoma of the
      thyroid.
AB  - Follicular carcinoma of the thyroid rarely manifests itself as a distant
      metastatic lesion, and, when present, is usually found in flat bones. A soft
      tissue metastasis is extremely rare, and synchronous metastases to the bone and
      soft tissue is not reported in the literature so far. We report such a case of a
      42-yr-old male, who presented with a goiter, scalp and forearm soft tissue
      swellings, and, fine needle aspiration cytology of all these swellings revealed a
      follicular neoplasm. A wide excision of the forearm swelling was carried out and
      the histopathology was consistent with features of metastatic follicular
      carcinoma of the thyroid. The main stay of treatment is surgical resection of the
      primary tumor. The various modalities of treatment of metastasis is discussed
      with a review of literature.

PMID- 14676457
TI  - Idiopathic calcium pyrophosphate dihydrate (CPPD) crystal deposition disease in a
      young male patient: a case report.
AB  - Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is a disease of
      the elderly and extremely rare in young individuals. If young people develop CPPD
      crystal deposition disease, it may be associated with metabolic diseases such as
      hemochromatosis, hyperparathyroidism, hypophosphatasia, hypomagnesemia, Wilson's
      disease, hypothyroidism, gout, acromegaly, and X-linked hypophosphatemic rickets.
      Therefore, in young-onset polyarticular CPPD crystal deposition disease,
      investigation for predisposing metabolic conditions is warranted. We report a
      case of a young male patient with idiopathic CPPD crystal deposition disease, who
      did not have any evidences of metabolic diseases after thorough evaluations. As
      far as we know, this is the first report of a young male patient presented with
      idiopathic CPPD crystal deposition disease.

PMID- 14676458
TI  - Sjogren's syndrome presenting as remitting seronegative symmetric synovitis with
      pitting edema (RS3PE): comment of the article by Choi et al.

PMID- 14676459
TI  - Serum estradiol concentration as measured by HPLC-RIA and bone mineral density in
      postmenopausal women during hormone replacement therapy.
AB  - OBJECTIVE: To determine the relationship between the serum estradiol
      concentration and bone mineral density (BMD) of the lumbar spine in
      postmenopausal women treated with conjugated equine estrogen (CEE) and
      medroxyprogesterone acetate (MPA) every other day and every day. METHODS: Eighty
      four postmenopausal women were randomly treated with hormone replacement therapy
      (HRT) every other day and every day. Forty-seven women received oral
      administration of 0.625 mg CEE and 2.5 mg MPA every other day, and 37 women
      received oral administration of 0.625 mg CEE and 2.5 mg MPA every day. BMD of the
      lumbar spine at 12 months and serum concentrations of estradiol and estrone at 6
      and 12 months after treatment were examined. RESULTS: The estradiol concentration
      in subjects treated every other day showed a significant (p < 0.001) positive
      correlation with the percentage change in lumbar BMD, while that in subjects
      treated every day was not correlated with the percentage change in BMD. The
      differences between serum estradiol concentrations after 12 months of treatment
      and initial serum estradiol values in women treated every other day and every day
      also showed a significant (p < 0.01 and 0.05, respectively) positive correlation
      with percentage changes in BMD. In women treated every other day, body mass index
      (BMI) in the subjects in whom BMD did not increase was significantly (p < 0.01)
      lower than that in the subjects in whom BMD did increase. CONCLUSIONS: The serum
      estradiol concentration in women treated every other day has a strong positive
      correlation with the percentage change in lumbar BMD, but a higher estradiol
      concentration may be needed for women in whom BMD did not increase with HRT every
      other day after due consideration of individual characteristics such as BMI.

PMID- 14676460
TI  - Three novel mutations in Japanese patients with 21-hydroxylase deficiency.
AB  - OBJECTIVE: This study analyzed the mutation of 21-hydroxylase deficiency (21-OHD)
      in 36 unrelated Japanese patients with congenital adrenal hyperplasia (CAH).
      METHODS: All the exons of the functional CYP21 gene (CYP21A2) were analyzed by
      polymerase chain reaction (PCR) and PCR direct sequencing. RESULTS: Apparent gene
      deletions and conversions were present in 23.6% of the 72 CAH alleles, in which
      the most frequent mutation was the IVS2-13 A/C>G (27.8%), followed by I172N
      (26.3%), consistent with the frequencies reported for other countries. Previously
      described mutations were not present in three unrelated cases. Sequence analysis
      of the complete functional CYP21A2 gene revealed three, not yet described
      mutations that represent a common pseudogene sequence. These three putative novel
      mutations are located in exon 1 (M1I), in exon 5 (1210-1211insT), and in exon 3
      (R124H). CONCLUSIONS: In this study, we have identified three putative novel
      mutations. It remains to be determined whether these three mutations are
      responsible for the significant number of as yet uncharacterized CAH patients in
      Japan.

PMID- 14676461
TI  - Normal bone mineral content in young adults with congenital adrenal hyperplasia
      due to 21-hydroxylase deficiency.
AB  - OBJECTIVE: To assess bone mineral content (BMC) and body composition in
      adolescents and young adults with congenital adrenal hyperplasia. METHODS: BMC,
      anteroposterior-projected bone area (BA), bone mineral density, and fat mass
      percentage were determined by dual-energy X-ray absorptiometry in 18 patients
      aged 18-33 years (8 females and 10 males) with 21-hydroxylase deficiency using a
      Hologic QDR 1000/W densitometer. RESULTS: BMC and bone mineral density for age
      were significantly reduced at -1.2 standard deviation scores (SDS; range from 
      2.8 to +4.1) and -1.1 SDS (range from -3.2 to +2.6), respectively. The BA for
      height was significantly increased at +1.7 SDS (range from -0.5 to +4.8), and the
      BMC for BA was normal at 0.3 SDS (range from -2.0 to +3.6). The median final
      height was significantly reduced at -1.6 SDS (range from -5.6 to +0.3), and the
      fat mass percentage was significantly increased at +1.5 SDS (range from -1.0 to
      +5.0). CONCLUSION: Our study population of young adults with 21-hydroxylase
      deficiency had a short stature and broad bones with a normal BMC and had an
      increased fat mass percentage.

PMID- 14676462
TI  - Effect of pamidronate treatment on vertebral deformity in children with primary
      osteoporosis. A pilot study using radiographic morphometry.
AB  - OBJECTIVE: Bisphosphonates are effectively used in treatment for primary
      osteoporosis in children. In the present study, we quantitatively evaluated the
      effect of pamidronate treatment on lumbar vertebrae in children with primary
      osteoporosis using radiographic morphometry. METHODS: Paired lateral radiographs
      of the lumbar spine were obtained before and after pamidronate treatment in 5
      children with primary osteoporosis. To characterize vertebral deformities,
      specific morphometrical ratios were calculated for vertebral bodies L1-L4.
      RESULTS: Significant reshape of lumbar vertebrae was observed: the concavity
      index (middle-anterior ratio) decreased from 55 to 36% (p = 0.006), and the
      anterior-posterior ratio (used as a surrogate of wedge deformity) decreased from
      25 to 11% (p = 0.001). CONCLUSIONS: Pamidronate treatment significantly
      influences the restoration of vertebral fractures in children with primary
      osteoporosis. The present study demonstrates that radiographic morphometry is a
      suitable tool for quantitative assessment of the vertebral deformities in
      childhood.

PMID- 14676463
TI  - Validation of a mathematical model predicting the response to growth hormone
      treatment in prepubertal children with idiopathic growth hormone deficiency.
AB  - OBJECTIVE: To validate a mathematical model developed by Ranke et al. (J Clin
      Endocrinol Metab 1999;84:1174-7783) to predict the GH response during the first
      years of GH replacement therapy. PATIENTS AND METHODS: 38 children with
      idiopathic GH deficiency (GHD) met all inclusion criteria for the prediction
      model, but the group differed in some characteristics from the cohort from which
      the model was derived. RESULTS: Using the model for the 1st year including
      maximum GH after stimulation and the equation for the 6th year, the predicted
      value corresponded well with actual height gain. Differences were found when the
      growth response of the 1st year excluding maximum GH and that of the 2nd-5th year
      were calculated, resulting in a significant underestimation of actual height gain
      (-0.63 to -1.07 cm/year). CONCLUSION: The mathematical prediction model tended to
      underpredict the growth response to GH treatment in our patients with pronounced
      GHD. The severity of GHD seems to be an important parameter for the 1st year
      prediction.

PMID- 14676464
TI  - Pathology and neurotransmitter abnormalities of dementia with Lewy bodies.
AB  - The neuropathology of dementia with Lewy bodies (DLB) is characterized by the
      presence of Lewy bodies (LBs) and Lewy neurites (LNs) in specific systems
      throughout the brainstem, diencephalon, basal ganglia and neocortex. DLB shares
      many features with Parkinson's disease (PD) with respect to LB distribution in
      the brainstem, and there is recent evidence that Lewy pathology (LP), which
      consists of LBs and LNs, may progress in a systematic fashion through the brain
      regardless of clinical phenotype. Increasing evidence supports a central role for
      LNs in Lewy neurodegeneration and engenders a 'neuritic dystrophy hypothesis'
      described herein. LP formation also occurs in Alzheimer's disease (AD) and other
      dementias, and it is unclear whether there is a common underlying pathophysiology
      in these diseases or if the LP merely represents a common final pathway.
      Cholinergic deficits are evident in both DLB and AD, with reductions in
      acetylcholine and abnormalities in nicotinic and muscarinic receptor expression
      in both diseases. Cholinergic deficits are greater in DLB than in AD, although
      generally there is less brain atrophy in DLB. The lower neurodegeneration and
      preservation of cholinergic receptors in DLB has important therapeutic
      implications because patients with DLB (vs. AD) may receive greater benefits from
      cholinergic pharmacologic therapy. Patients with DLB who display parkinsonian
      signs have severe dopamine neurotransmitter deficiencies similar to those in
      patients with PD, although the manifestation of these deficiencies is different.
      Both groups have striatal dopamine transporter deficiencies, but the striatal
      dopamine D2 receptors are reduced in DLB patients compared with PD and control
      subjects. D2 receptor deficiencies in DLB may be the cause of the relative lack
      of response to levodopa treatment and the severe adverse reaction to neuroleptics
      in these patients.

PMID- 14676465
TI  - Definition and diagnosis of dementia with Lewy bodies.
AB  - Significant advances have been made in neuropathologic identification procedures
      for dementia with Lewy bodies (DLB), but difficulties remain in clinical
      diagnosis. Consensus criteria state that the core features of DLB are fluctuating
      cognition with pronounced variation in attention and alertness, recurrent visual
      hallucinations and spontaneous motor features of parkinsonism. At least two of
      these features must be present for the diagnosis of probable DLB. Assessments of
      the validity of the consensus criteria against autopsy generally indicate high
      specificity but varying sensitivity. More detailed assessments of core diagnostic
      features or better operationalization, particularly of fluctuating cognition, may
      help improve the diagnostic guidelines. Greater utilization of some features
      described as supporting the diagnosis (such as auditory hallucinations) and the
      potential inclusion of additional symptoms (such as REM sleep behavioral
      disorder) also may be useful. In addition, the potential role of more detailed
      neuropsychology and neuroimaging in the diagnostic process needs to be evaluated,
      although it is important that changes to the diagnostic criteria are based on
      empirical evidence. Other key issues pertain to the classification of DLB
      patients with concurrent Alzheimer's disease and the differentiation of DLB and
      Parkinson's disease dementia based on less than a 1-year history of parkinsonism
      preceding the dementia.

PMID- 14676466
TI  - Neuroimaging as a diagnostic tool in dementia with Lewy bodies.
AB  - Due to similar presenting symptoms, many physicians find it difficult to
      distinguish cases of dementia with Lewy bodies (DLB) from Alzheimer's disease or
      Parkinson's disease with dementia. The pathologic diagnosis of DLB has improved
      because of the discovery of probes for alpha-synuclein, a protein found in Lewy
      bodies. However, pathologic diagnosis can be employed postmortem only, and
      therefore diagnostic techniques that can be employed to guide patient management
      are still needed. Consensus criteria have been developed for establishing a
      clinical diagnosis of DLB, but they lack sensitivity. Therefore, a review of the
      recent literature was conducted to establish whether neuroimaging studies are
      useful diagnostic tools to help differentiate these syndromes. At least six types
      of tests can be used to image the brain of patients with dementia. Structural
      studies (x-ray, magnetic resonance imaging and computerized tomography) can
      disclose the presence of stroke sequelae and other lesions, whereas functional
      studies (magnetic resonance spectroscopy, positron emission tomography and single
      photon emission computed tomography) can disclose metabolic and blood flow
      alterations that may be characteristic for different types of dementia. Although
      more formal studies are needed to confirm that these imaging techniques are
      reliable diagnostic tools for DLB and permit the establishment of guidelines for
      their use, neuroimaging techniques currently are being employed in practice to
      differentiate dementia types as a guide to treatment.

PMID- 14676467
TI  - Pharmacologic treatment expectations in the management of dementia with Lewy
      bodies.
AB  - Recently recognized as an entity separate from Alzheimer's disease (AD) and
      Parkinson's disease with dementia, dementia with Lewy bodies (DLB) is a frequent
      cause of dementia. It is characterized by progressive cognitive decline and
      attention deficits, but in contrast to AD, the cognitive changes typically
      fluctuate over time. Patients with DLB often experience Parkinson-like
      spontaneous motor features as well as recurrent visual hallucinations. Another
      frequent finding in DLB is rapid eye movement (REM) sleep disorder. Ideally, each
      of the major symptom domains associated with DLB (behavioral, motor, and
      cognitive) would be treated, but drug interactions in these patients are a
      serious concern. In addition, many patients with DLB are hypersensitive to
      neuroleptics, which can induce severe extrapyramidal and other symptoms-
      sometimes ending in death. Compared with conventional neuroleptics, the newer
      atypical antipsychotic agents may be associated with lower rates of
      extrapyramidal side effects. Cholinergic deficits in DLB are even more severe
      than in AD, whereas the extent of cerebral atrophy and neuronal damage may be
      less. These observations and emerging clinical data support the treatment of DLB
      with acetylcholinesterase inhibitors. Encouraging results have been obtained from
      studies of DLB patients treated with rivastigmine, donepezil, and galantamine,
      but large-scale, controlled trials are needed to confirm the efficacy and safety
      of acetylcholinesterase inhibitors in patients with DLB.

PMID- 14676468
TI  - Efficacy and safety of galantamine in patients with dementia with Lewy bodies: a
      12-week interim analysis.
AB  - Observations on the neurochemistry of dementia with Lewy bodies (DLB) have
      suggested that cholinesterase inhibitors (ChEIs) might be beneficial in treating
      some clinical symptoms of DLB. A 24-week, multicenter open-label study was
      designed to assess the safety and efficacy of the ChEI galantamine in patients
      with DLB, and an interim analysis of results was performed at 12 weeks. Efficacy
      analyses were performed on data from 25 patients. Scores on the Neuropsychiatric
      Inventory (NPI-12) improved (decreased) by 7.52 points over the 12 weeks
      (marginally significant, p = 0.061). NPI-12 scores decreased by half in 12 of the
      25 patients. Highly significant improvement was observed in scores on the NPI-4
      subscale (delusions, hallucinations, apathy, and depression: p = 0.003). Scores
      on the Clinician's Global Impression of Change (CGIC) improved by 0.95 points
      (significant, p = 0.02). Improvements also were found in secondary efficacy
      variables, including cognitive, functional, activities of daily living, sleep and
      confusion assessments. Motor scores, as measured by the UPDRS motor subscale,
      showed mild improvement, which demonstrates that galantamine has no adverse
      effect on parkinsonian symptoms. Adverse events generally were transient and of
      mild-to-moderate intensity. Two of the 25 patients discontinued galantamine
      because of nausea and anorexia. One serious adverse event was recorded, but it
      was judged to be unrelated to the study medication.

PMID- 14676469
TI  - Transcription, translation, and transitions.

PMID- 14676470
TI  - Deafness genes and their diagnostic applications.
AB  - Hearing impairment (HI) is clinically and genetically very heterogeneous, and
      auditory genes are discovered at a very rapid pace. The identification of
      deafness genes is enabling us to understand the molecular process of hearing, and
      it offers prospects for DNA testing of HI. However, the routine application of
      these tests is hampered by the large number of genes involved in HI and by the
      fact that molecular screening of these genes is often quite expensive and time
      consuming. An important gene that should be considered in congenital or childhood
      onset autosomal recessive HI is GJB2 since mutations in this gene account for at
      least 50% of this type of HI. In the present review, we describe the known
      deafness genes and we provide an overview of the current, routinely used
      diagnostic DNA tests.

PMID- 14676471
TI  - Mutation in mitochondrial DNA as a cause of presbyacusis.
AB  - Much of the hearing loss that occurs in old age is likely to be due to the long
      term deterioration of the mitochondria in the different structures of the
      cochlea. The current review surveys some of the basic information on mitochondria
      and mitochondrial DNA, as a background to their possible involvement in
      presbyacusis. It is likely that oxygen radicals damage mitochondrial DNA and
      other components of the mitochondria, such as their proteins and lipids. This
      further compromises both oxidative phosphorylation and the repair processes in
      mitochondria, setting up a vicious cycle of degradation. Evidence is presented
      from inherited point mutations on the possibly most critical sites for mutations
      in mitochondrial DNA associated with hearing loss. It is suggested that random
      sorting and clonal expansion of mutations both maintain the integrity of the pool
      of mitochondrial DNA molecules and give rise to the apoptosis that leads to loss
      of vulnerable cells, and hence to deafness. It is moreover suggested that
      apoptosis of the vulnerable cells of the inner ear may to some extent be
      preventable, or at least delayed.

PMID- 14676472
TI  - A novel mutation identified in the DFNA5 gene in a Dutch family: a clinical and
      genetic evaluation.
AB  - A novel DFNA5 mutation was found in a Dutch family, of which 37 members were
      examined. A nucleotide substitution was identified in the splice acceptor site of
      intron 7, leading to skipping of exon 8 in part of the transcripts. The mutation
      was found in 18 individuals. Sensorineural hearing impairment was non-syndromic
      and symmetric. In early life, presumably congenitally, hearing impairment
      amounted to 30 dB in the high frequencies. Progression was most pronounced at 1
      kHz (1.8 dB/year). Speech recognition was relatively good with a phoneme score of
      about 50% at the age of 70. Onset age was 37 years, and recognition deteriorated
      by 1.3% per year. The recognition score deteriorated by 1.0% per decibel
      threshold increase from a mean pure-tone average (PTA at 1, 2 and 4 kHz) of 63 dB
      onwards. Vestibular function was generally normal. The second mutation identified
      in the DFNA5 gene results in hearing impairment, similar to that in the original
      DFNA5 family in terms of pure-tone thresholds, but with more favourable speech
      recognition.

PMID- 14676473
TI  - A novel connexin 26 mutation associated with autosomal recessive sensorineural
      deafness.
AB  - Mutations in the connexin 26 (Cx26) gene (GJB2) are a common cause of hereditary
      hearing impairment which affects approximately 1 in 2000 newborn children. We
      report the identification of a novel Cx26 point mutation (439 G-->A) linked to
      familial, autosomal recessive, sensorineural hearing loss. This missense mutation
      (E147K) is located in the highly conserved, putative K(+) channel lining sequence
      of the third transmembrane domain (TM3) of Cx26. Hearing impairment associated
      with this mutation was congenital, moderate to profound and showed no signs of
      progressive deterioration.

PMID- 14676475
TI  - [The effect of topical ascorbic acid application on the healing of rat tympanic
      membrane perforations].
AB  - OBJECTIVES: We investigated the effect of topical administration of ascorbic acid
      on the healing process of tympanic membrane perforations in rats. DESIGN AND
      METHODS: Thermal myringotomy was induced in both ears of 22 albino rats. The
      right and left ears were assigned to topical applications of ascorbic acid and
      saline solution, respectively. The same procedure was performed after 48 hours.
      Perforations were examined daily by otomicroscopy and healing periods were
      determined. For histopathologic examination, a single rat in which closure of the
      tympanic membranes was not completed was sacrificed on days 5, 7, 10, and 12.
      Data were analyzed with the use of the Student's t-test. RESULTS: The mean
      durations of healing in the right and left ears were 7.6 and 8.3 days,
      respectively. No significant differences were found between the applications of
      ascorbic acid and saline solution with regard to the duration of closure and
      histopathologic healing criteria. CONCLUSION: Our data suggest that topical
      application of ascorbic acid have no beneficial effect on the healing of rat
      tympanic membrane perforations.

PMID- 14676474
TI  - Sex-related hearing impairment in Wolfram syndrome patients identified by
      inactivating WFS1 mutations.
AB  - This study examined the audiovestibular profile of 11 Wolfram syndrome patients
      (4 males, 7 females) from 7 families, with identified WFS1 mutations, and the
      audiometric profile of 17 related heterozygous carriers of WFS1 mutations.
      Patients with Wolfram syndrome showed a downsloping audiogram and progressive
      hearing impairment. None of the carriers had sensorineural hearing loss. Two
      patients with missense (non-inactivating) mutations in WFS1 had normal hearing
      and mild symptoms of Wolfram syndrome and were excluded from the analyses. Of the
      identified patients with inactivating WFS1 mutations, 5 female patients were
      significantly more hearing impaired than four male patients (p < 0.05). Female
      patients showed hearing impairment progressing by 1.5-2.0 dB HL per year for the
      low frequencies and 4.0-4.5 dB HL per year for the mid and high frequencies. The
      age of onset (90% phoneme recognition score) was 21 years and the onset level 78
      dB HL. The deterioration rate was 4.0% per year and the deterioration gradient
      1.4% per dB HL. One of the 6 examined patients had vestibular areflexia.

PMID- 14676476
TI  - [The management of pharyngocutaneous fistulas after total laryngectomy and the
      factors affecting their incidence].
AB  - OBJECTIVES: This study sought to determine the incidence and etiologic factors of
      pharyngocutaneous fistulas occurring after total laryngectomy. PATIENTS AND
      METHODS: A total of 138 patients (136 males, 2 females; mean age 59.5 years;
      range 36 to 83 years) underwent total laryngectomy for squamous cell carcinoma.
      Risk factors and the management of pharyngocutaneous fistulas were assessed
      together with durations in relation to fistula occurrence, oral feeding,
      hospitalization, and healing. RESULTS: Pharyngocutaneous fistulas were seen in 37
      patients (26.8%). Significantly high rates of fistula occurrence were detected in
      patients with alcohol consumption (p=0.032), and in those who underwent partial
      pharyngectomy (p=0.058) or bilateral neck dissection (p=0.049) along with total
      laryngectomy. The occurrence of fistulas was significantly associated with
      prolonged lengths of time for oral feeding and hospital stay (p<0.001). Fistulas
      were repaired surgically in 24.3% of patients, in whom the time to oral feeding
      was significantly shorter than that of patients who received local wound care
      (p=0.03). CONCLUSION: Our data show that early surgical intervention is more
      beneficial in preventing further morbidity associated with pharyngocutaneous
      fistulas.

PMID- 14676477
TI  - [The effect of neck metastasis on survival following surgery for laryngeal
      cancer].
AB  - OBJECTIVES: We evaluated the effect of neck metastasis on the survival rate of
      patients who underwent surgery for laryngeal cancer. PATIENTS AND METHODS: A
      total of 256 patients who had undergone surgery between 1995 and 1999 were
      retrospectively reviewed. Of these, 186 patients (72%; 185 males, 1 female; mean
      age 57.5 years) who were accessible for follow-up were evaluated with respect to
      the localization and type of the primary tumor, neck metastasis, surgical
      procedures, and the survival. Survival rates were determined by the Kaplan-Meier
      method and compared by the log-rank test. The rates of neck metastasis and
      extracapsular spread in survivors and non-survivors were compared with the use of
      the chi-square test. The minimum follow-up period was two years (mean 41.2
      months). RESULTS: Twenty-nine patients died from locoregional recurrences or
      distant metastasis and six patients died from other causes. The cumulative
      survival period was 69 months (75 months and 54 months with or without neck
      metastasis, respectively; log rank test 27.96, p<0.0001). The rates of neck
      metastasis and extracapsular spread in survivors (22%, 33/151; 7%, 10/151) and
      non-survivors (69%, 20/29; 59%, 17/29) were significantly different (p<0.001).
      CONCLUSION: Neck metastasis and cervical recurrence were found as the most
      important factors affecting the results of laryngeal cancer surgery.

PMID- 14676478
TI  - Atypical presentation of Kaposi's sarcoma in the external ear.
AB  - We presented a case of Kaposi's sarcoma that occurred in the external ear of a 36
      year-old Caucasian man. He was otherwise healthy without a history of any
      predisposing factors. He had a nodular lesion in the left ear, of three-month
      duration. The lesion was excised completely. Histologic and immunohistologic
      findings were consistent with a diagnosis of Kaposi's sarcoma. Serologic analyses
      were negative for anti-HIV antibody and anti-cytomegalovirus IgM and IgG and
      blood count was normal. Differential count of leucocytes and immunoglobulin
      electrophoresis were normal. During a two-year follow-up, no recurrences,
      development of new lesions, or HIV seroconversion were detected. To our
      knowledge, this case is the first to report a solitary lesion of Kaposi's sarcoma
      occurring in the helix of the ear in a healthy young patient.

PMID- 14676479
TI  - [Primary Hodgkin's lymphoma of the parotid gland: a case report].
AB  - Primary Hodgkin's lymphoma of the parotid gland is rare. A twenty-one-year-old
      man presented with a lesion that recurred two years after an excisional biopsy
      for a parotid gland mass. He underwent superficial parotidectomy. Frozen section
      examination suggested a diagnosis of Hodgkin's lymphoma. The patient was treated
      by radiotherapy. A complete recovery was obtained after a 27-month follow-up.

PMID- 14676480
TI  - [Fibrous dysplasia in the head and neck region: a report of three cases].
AB  - Fibrous dysplasia is a benign process in which bone expands due to abnormal
      development of fibrous tissue. Involvement of single or multiple bones may occur.
      Common sites of involvement in the head and neck region are the maxilla and the
      mandible. Temporal bone involvement is rare. We report three patients with
      fibrous dysplasia, in whom the temporal bone (female, age 35 years) and the
      maxilla (male, age 17 years; female, age 20 years) were affected. The former
      underwent mastoidectomy, while the latter two patients underwent mass excision
      with lateral rhinotomy. No recurrences were detected within long-term follow-ups.

PMID- 14676481
TI  - [A case of laryngeal chondroradionecrosis].
AB  - Chondroradionecrosis is one of the rare but important complications of radiation
      therapy for laryngeal carcinoma. A sixty-one-year-old male patient with glottic
      carcinoma (T1bN0M0) was treated with radiotherapy because he did not give consent
      to surgery. He developed difficulty in breathing and halitosis three months
      following radiotherapy. Radiologic and clinical signs were consistent with a
      diagnosis of laryngeal chondroradionecrosis. Medical treatment with steroids and
      antibiotics did not relieve his symptoms, so total laryngectomy was performed. No
      postoperative complications were seen. The surgical specimen was free of tumor.

PMID- 14676482
TI  - Case report: Two cases of placenta previa terminated at 18 weeks' gestation.
AB  - Placenta previa is associated with increased maternal and fetal morbidity, caused
      primarily by hemorrhage, making an accurate diagnosis very important. However,
      diagnosis and treatment remain difficult, especially in the second trimester. We
      treated two cases with placenta previa at 18 weeks' gestation. In both patients,
      the cervical os was still closed when bleeding increased, necessitating emergency
      cesarean section. Postoperative course and the course of the subsequent pregnancy
      were uneventful. Terminating the pregnancy at the time of worsening of symptoms
      even in the second trimester should be considered as an option in the treatment
      of placenta previa.

PMID- 14676483
TI  - Deletion of the SMN1 and NAIP genes in Vietnamese patients with spinal muscular
      atrophy.
AB  - The SMN1 and NAIP genes are related to the development of spinal muscular atrophy
      (SMA), which is characterized by degeneration of motor neurons leading to
      progressive muscular weakness and atrophy. The SMN1 gene is homozygously deleted
      in most SMA patients, and now recognized as a responsible gene for SMA. The NAIP
      gene is often deleted in the SMA patients with the severest form of SMA, and now
      considered to be a modifying factor of the severity of SMA. Our previous study of
      five Vietnamese SMA patients showed that the SMN1 gene deletion was detected in
      one patient, although the NAIP gene deletion was not detected in any patients. In
      this study, we analyzed 12 Vietnamese SMA patients who were not enrolled in the
      previous study. The SMN1 gene was homozygously deleted in six out of 12 patients,
      and the NAIP gene deletion was detected in five patients. Taken together with our
      previous data, the SMN1 gene deletion was detected in seven out of 17 Vietnamese
      SMA patients and the NAIP gene deletion in five out of 17 Vietnamese SMA
      patients. These studies suggest that the SMN1 and NAIP gene deletions are not
      rare in Vietnamese SMA patients. Thus, the confirmation of SMA-related gene
      deletion will also be a useful tool for the diagnosis of SMA in Vietnam.

PMID- 14676484
TI  - Minireview: Up-date management of non responder to clomiphene citrate in
      polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a heterogeneous disorder in which chronic
      anovulation is a common feature despite the presence of multiple micro-
      structures in the ovaries. A growing body of evidence has suggested that serum
      hyperinsulinemia contributes to the excess ovarian androgen secretion observed in
      women with PCOS. The standard therapy for anovulatory women with PCOS is oral
      administration of clomiphene citrate (CC). However, a significant proportion of
      women with PCOS fail to ovulate with the use of standard dosage of CC and are
      called CC-resistant PCOS. The recent introduction of the insulin-sensitizing
      agents as adjuvants to clomiphene citrate and gonadotropins has changed the
      treatment strategy. This is a comprehensive review of the literature, with an
      emphasis on the role of hyperinsulinemia in the pathogenesis of PCOS and on
      randomized controlled trials of the medical and surgical treatment options for
      women with CC-resistant PCOS. Although both standard and novel treatments were
      addressed in the present review, special attention was paid to the evidence in
      support of the recent introduction of insulin-sensitizing agents in the
      management of anovulatory woman with CC-resistant PCOS.

PMID- 14676485
TI  - Characterization of nonfatal events and injuries resulting from youth violence in
      patients presenting to an emergency department.
AB  - OBJECTIVES: To characterize the circumstances of youth intentional violence in
      emergency department patients and compare circumstances of events between gender
      and age groups. METHODS: Cross-sectional survey and chart review of a 9-month
      consecutive sample of 8-year to 24-year-old intentionally injured patients
      (excluding child abuse or domestic violence) in 3 emergency departments. RESULTS:
      Four hundred twenty-six patients were included in the study. Most events were
      fights and most occurred in the street. Fists, hands, and feet were the most
      common weapon, and contusions or abrasions the most common injury. Most events
      involved only 2 people, and most incidents involved friends or acquaintances.
      Events involving 8 to 14 year olds were more likely to occur in school, to
      involve only fists, hands, or feet, and involve a friend. Eight to 14 year olds
      were less likely to use a firearm. Among the younger group, females were more
      likely than males to be injured in an assault, sustain a contusion or abrasion,
      and be involved in an incident with multiple participants. Older females were
      more likely than males to be involved in an event in the home, and sustain a
      contusion, abrasion, or bite. CONCLUSIONS: This study characterizes the
      circumstances of youth intentional violence that result in emergency department
      visits for injuries. Although similarities exist between different age groups and
      genders, some key differences between the groups are illustrated. Understanding
      the differences between violent events in different age groups and genders may
      help clinicians recognize injury patterns and possibly guide alternative
      interventions.

PMID- 14676486
TI  - The safe and effective use of propofol sedation in children undergoing diagnostic
      and therapeutic procedures: experience in a pediatric ICU and a review of the
      literature.
AB  - OBJECTIVES: To describe our experience using propofol sedation to facilitate
      elective diagnostic and therapeutic procedures, and to document the safety
      profile of propofol in this setting. DESIGN: Retrospective consecutive case
      series and review of the literature. SETTING: Pediatric intensive care unit of a
      United States Navy tertiary care medical center. PATIENTS: Children receiving
      propofol for procedural sedation over an 18-month period. OUTCOME MEASURES:
      Descriptive features of sedation including adverse events. RESULTS: During the
      study period, 91 children received propofol to facilitate the performance of 110
      medical procedures. The mean induction dose was 2.41 mg/kg, the mean infusion
      rate was 179.3 microg/kg/min, and the mean total dose of propofol administered
      was 4.23 mg/kg. In all cases, sedation was successfully achieved. The average
      length of stay in the PICU was 108.4 minutes. Three children (3.3%) had transient
      episodes of oxygen desaturation that improved with repositioning of the airway.
      No child required placement of an endotracheal tube. Three (3.3%) children
      experienced hypotension requiring a decrease in the infusion rate of propofol and
      a 10-mL/kg bolus infusion of normal saline. No cardiac arrhythmias or adverse
      neurologic effects secondary to propofol infusion were identified. CONCLUSIONS:
      Pediatric intensivists can safely and effectively administer propofol to
      facilitate the performance of diagnostic and therapeutic procedures outside the
      operating room setting.

PMID- 14676487
TI  - Which IO model best simulates the real thing?
AB  - OBJECTIVE: To determine which model best simulates the actual IO procedure in
      children. METHODS: Forty emergency and critical care physicians with significant
      IO experience (6 or more IO procedures) in real children were recruited at 4
      academic centers. Study subjects were provided with a kit containing 15 gauge IO
      needles and 5 IO models; a plastic IO doll leg (PL), a turkey femur/thigh (TT), a
      turkey tibia/drumstick (TD), a chicken femur/thigh (CT), and a pork rib (PR).
      Study participants scored the similarity of the bone model to that of placing an
      IO in a child (0 = no experience, 1 = perfect simulation, 2 = excellent, but not
      perfect, 3 = good, 4 = moderate, 5 = poor) and the hardness of the bone (H = too
      hard, J = just right, S = too soft) for each age group (preterm, newborn, 1-4
      months, 5-12 months, 12-36 months, 3-6 years, 6-12 years, and >12 years old) of
      whom they had previous experience. Mean scores were calculated and compared to
      determine which model provided the best simulation. RESULTS: After excluding zero
      scores, overall mean scores for the CT, TD, TT, PL, and PR models were 3.2, 3.3,
      3.3, 3.3, and 4.4 (P < 0.001), respectively. The pork rib had the worst score in
      all age groups, while the other 4 models had roughly similar scores. All models
      had substantial percentages of the models classified as too hard or too soft,
      except for the pork rib, which was predominantly too hard. CONCLUSIONS: For IO
      research and teaching purposes, bone models should be age appropriate. This study
      suggests that there is great variability in preference with the chicken, turkey,
      and plastic models.

PMID- 14676488
TI  - Long-term effects on tibial growth after intraosseous infusion: a prospective,
      radiographic analysis.
AB  - BACKGROUND: Evaluate, by radiographic analysis, tibial growth after an
      intraosseous infusion (IOI) in a pediatric population. METHODS: We performed a
      prospective simple blind study, between January 1, 1994, and July 1, 2001, which
      included pediatric patients who needed an intraosseous trocar in emergency
      situations. During the follow-up, roentgenographs were performed. On each
      radiologic view, different measurements were carried out: anterior and lateral
      tibial length, anterior and lateral width at 2 diaphyseal levels. We compared the
      anterior length values to those published in the Anderson et al tables. When only
      one tibia was punctured, the mean measurements were compared with the control leg
      measurements using a paired t test. RESULTS: The initial population included 78
      patients. Of these 78 subjects, 42 died, 10 families could not be contacted, and
      one refused to participate. Two children were excluded because they had other
      conditions that could influence tibial growth. The study included 23 children.
      The puncture site was the proximal tibia. The mean age was 18.6 months at the
      time of IOI, the mean time of infusion was 5 hours, and the mean perfused volume
      was 225 mL. The mean radiologic follow-up time was 29.2 months. When compared
      with the Anderson et al tables, all the anterior length values were within the
      95% confidence interval. For the other measurements, the statistical analysis
      showed no significant difference between punctured and control legs. CONCLUSION:
      There is no long-term effect on tibial growth after an IOI when the IO trocar is
      properly placed.

PMID- 14676489
TI  - Esophageal food impaction in children.
AB  - OBJECTIVES: To determine the clinical presentation, radiographic, endoscopic and
      manometric findings, and clinical outcome of esophageal food impaction (EFI) in
      pediatric patients. METHODS: We retrospectively reviewed the clinical course of
      12 pediatric patients with EFI over a 10-year period. RESULTS: All 12 patients
      described initially presented to our emergency department for care. Four patients
      (25%) required previous endoscopic intervention for disimpaction of EFI. Eleven
      required endoscopic removal of their EFI, and 1 patient's food impaction resolved
      spontaneously. The mean duration of food impaction was 20 hours prior to
      endoscopic intervention. Endoscopy demonstrated an esophageal stricture in 1
      patient with a history of trisomy 21 and tracheoesophageal fistula repair. While
      there was no visual evidence of esophagitis in any patient, 5 of 7 had histologic
      evidence of esophagitis. Upper gastrointestinal series demonstrated the esophagus
      to be anatomically normal in 10 of 12 patients (83%); 1 patient had an esophageal
      stricture and another an esophageal web. Four of 8 patients studied had
      nonspecific esophageal motility abnormalities. CONCLUSIONS: EFI in children is
      not generally associated with underlying esophageal anatomic abnormalities.
      Esophagitis and nonspecific esophageal motility disorder abnormalities may be
      etiologic factors. Endoscopic removal of the EFI was safe and effective and is
      recommended as there is little likelihood of spontaneous resolution of EFI in
      children.

PMID- 14676490
TI  - Barriers to pediatric advanced life support training in the state of Alabama.

PMID- 14676491
TI  - Wandering spleen: a rare cause of abdominal pain.
AB  - Torsion of a wandering spleen is a rare cause of abdominal pain in children. The
      most common presentation is acute abdominal pain, although signs and symptoms
      vary widely. Due to the risk of splenic infarction, rapid and accurate diagnosis
      is essential. Wandering spleen and splenic torsion can be diagnosed by Doppler
      ultrasound and CT scan. Treatment options include splenopexy or splenectomy. This
      case describes a 9-year-old girl with torsion of a wandering spleen, complicated
      by splenic infarction and managed by splenectomy.

PMID- 14676492
TI  - Fulminant bacterial meningitis complicating sphenoid sinusitis.

PMID- 14676493
TI  - Perforated Meckel's diverticulum in a neonate mimicking necrotizing
      enterocolitis.

PMID- 14676494
TI  - Activated charcoal laryngitis in an intubated patient.
AB  - Activated charcoal is useful in the management of poisonings, but it is not
      harmless. We report the case of a patient who developed obstructive laryngitis
      secondary to aspiration of activated charcoal with a protected airway. CASE: A 2
      year-old girl presented acute mental alteration secondary to presumed poisoning.
      Mechanical ventilation was initiated, and a single dose of activated charcoal was
      administered. She had an episode of vomiting during the respiratory weaning.
      Black-tinted tracheal secretions were suctioned through the tube immediately.
      Pulmonary auscultation and radiologic examination were normal. When she was
      extubed, she developed obstructive laryngitis. Fiberbronchoscopy was performed
      and showed edema and a significant amount of charcoal particles on the
      epiglottis, arytenoids, and arytenoepiglottic folds. Charcoal particles were
      removed by bronchoscopy successfully. Later evolution was normal, and no symptoms
      were present when she was discharged at home. COMMENTS: Obstructive laryngitis is
      a new major complication of activated charcoals use in upper airway. It is
      remarkable that this complication occurred in a protected airway. Charcoal is not
      an innocuous agent. This case shows that nasogastric administration of activated
      charcoals presents a significant degree of risk.

PMID- 14676495
TI  - Kawasaki disease.

PMID- 14676496
TI  - Measurement of central venous pressure from a peripheral vein in infants and
      children.
AB  - BACKGROUND: Previous studies in adults have demonstrated a clinically useful
      correlation between central venous pressure (CVP) measured from a peripheral
      intravenous catheter and that measured from a central venous catheter. The
      current study prospectively compares CVP measurements from a central catheter and
      a peripheral catheter in infants and children. METHODS: The study cohort included
      patients younger than 12 years presenting for a surgical procedure for which
      central venous access was necessary. CVP was measured simultaneously every 15
      minutes for a total of 10 measurements from the central venous catheter and the
      peripheral IV catheter using standard pressure transducers, which were zeroed at
      the phlebostatic axis. RESULTS: The cohort for the study included 30 infants and
      children ranging in age from 1 to 12 years. The peripheral IV catheter from which
      the CVP was measured ranged from a 24 to an 18 gauge. In 5 of the patients, there
      was no increase in the CVP value from the peripheral IV catheter in response to a
      sustained inspiratory breath or occlusion of the extremity above the catheter. In
      these 5 cases, the difference between the CVP measured from the central and
      peripheral catheter was 16 +/- 5 mm Hg versus 5 +/- 3 mm Hg in the other 25
      patients (P < 0.0001). In the remaining 25 patients, the difference between the
      CVP measured from the peripheral and the central site was 5 +/- 3 mm Hg. There
      was no difference in the central versus peripheral CVP measurement depending on
      the size of the IV cannula, its location (upper versus lower extremity), or the
      patient's position. CONCLUSION: CVP can be measured from a peripheral IV catheter
      in infants and children provided that there is continuity with the central venous
      compartment demonstrated by showing an increase in the CVP from the peripheral IV
      catheter in response to a sustained inspiratory effort and by occlusion of the
      extremity above the site of the catheter.

PMID- 14676497
TI  - Mild traumatic brain injury in children: practice guidelines for emergency
      department and hospitalized patients. The Trauma Program, The Children's Hospital
      of Philadelphia, University of Pennsylvania School of Medicine.
AB  - Mild traumatic brain injury (MTBI) is a frequent occurrence in children. Current
      practice in treating such injuries varies in terms of evaluative studies, length
      of observation, need for inpatient hospitalization, sports restrictions, and
      follow-up. A multidisciplinary panel of experts from a level I pediatric trauma
      center was convened to develop and implement a clinical pathway to improve the
      quality and consistency of care provided to children after MTBI. The clinical
      pathway, based on current literature and expert consensus, provides a management
      guideline for the management of MTBI in the emergency department through
      discharge. The algorithm provides reasonable management options based on the
      child's clinical presentation, history, and age. Exemplary care of children and
      their families after MTBI includes appropriate patient/family education.
      Standardized discharge instructions for MTBI were developed to provide
      comprehensive information in a succinct and easy-to-read format. The instructions
      for home management focus on expected symptoms and guidance for when to seek
      further medical attention. They also incorporate injury prevention, return to
      sports guidelines, and resources for additional information.

PMID- 14676498
TI  - Pain in the paediatric emergency department.

PMID- 14676499
TI  - (Some of the) lessons learned from Peter Safar.

PMID- 14676500
TI  - Femoral nerve block for femoral shaft fractures in a paediatric Emergency
      Department: can it be done better?
AB  - BACKGROUND: The relatively simple technique of administering a femoral nerve
      block is known to be quick, safe and effective in providing prolonged analgesia
      to children with femoral shaft fracture. Although medical literature supports its
      use in the emergency setting, no studies have been conducted on how this is
      undertaken in practice. OBJECTIVE: The aim of this study is to describe the
      practice of femoral nerve block in previously well children who present to our
      Emergency Department with femoral shaft fracture. SETTING: This study was
      conducted at the Emergency Department of a tertiary paediatric hospital in
      Sydney, Australia. METHODS: A retrospective descriptive study was conducted by
      gathering data on all patients presenting to the Emergency Department between 1
      January 1996 and 1 July 2001 with traumatic fracture to the femoral shaft.
      Whether femoral nerve block had been performed in the emergency setting; the time
      taken for femoral nerve block to be performed; the type of local anaesthetic
      used; the dose of local anaesthetic administered, and the level of training and
      area of expertise of doctors performing the femoral nerve block were determined
      from the clinical records. One-way analysis of variance and Student's t-tests
      were conducted to compare the average dosages of local anaesthetic used by the
      different medical sub-specialities involved. Student's t-tests were applied to
      analyse the time differences for performing femoral nerve block between emergency
      and non-emergency-based medical staff. RESULTS: The majority (111) of the 117
      patients who met the inclusion criteria for the study had isolated femoral shaft
      fractures (94.9%). Femoral nerve blocks were performed in 97 of our study
      patients (82.9%). No correlation was found between the age of the child and the
      time taken for a femoral nerve block. In 76 cases in which a femoral nerve block
      was given (64.9%), a member of staff external to the Emergency Department
      performed the procedure. The average time taken for a femoral nerve block to be
      performed for non-Emergency Department medical staff was significantly longer
      than for Emergency Department medical staff. In only 37 cases (31.9%), was a
      femoral nerve block administered within an hour of the time of triage. Doses used
      by non-anaesthetists were lower than those used by anaesthetists. CONCLUSION:
      There is unnecessary delay in carrying out this procedure for children with
      fractures to the femoral shaft. A significant degree of reliance on staff
      external to the Emergency Department was reported. This paper supports increased
      training and supervision to promote the more widespread and prompt use of femoral
      nerve blocks as an important standard of care for the Emergency Department.

PMID- 14676501
TI  - Pain assessment in the paediatric Emergency Department: whose view counts?
AB  - OBJECTIVES: To compare patient, guardian and professional assessment of acute
      pain in children presenting to an Emergency Department, and to examine whether
      there was a correlation between the scores obtained using the Faces and linear
      scales for each group. METHODS: A prospective, observational cohort study of 73
      children aged 4-14 years attending a paediatric hospital Emergency Department
      between March and April 2002 with pain caused by an acute injury. The child's
      pain on admission, as estimated by the child, their guardian and a healthcare
      professional (nurse/doctor/emergency nurse practitioner) was recorded using a
      Faces scale and a linear scale. RESULTS: Professionals consistently score pain
      lower [median linear scale score 3.1; interquartile range (IQR) 1.6-5.3] than do
      patients (6.6; 4.9-7.4) or guardians (6.0; 3.9-7.1) using both linear and Faces
      scales. There is a significant correlation between pain scores obtained using the
      two scales for professionals [Spearman R value 0.88; 95% confidence interval (CI)
      0.82-0.93], guardians (0.83; 0.74-0.89) and patients (0.42; 0.21-0.59).
      CONCLUSION: Professionals score pain lower than do children or guardians. Similar
      pain scores are obtained using both a Faces and a linear scale. This study offers
      no support for the introduction of a uniform pain assessment tool in a paediatric
      Emergency Department setting.

PMID- 14676502
TI  - Inadequate ventilation of patients with severe brain injury: a possible drawback
      to prehospital advanced trauma care?
AB  - OBJECTIVES: To assess the appropriateness of arterial carbon dioxide tension
      control in a group of 92 patients with traumatic brain injury who, despite
      receiving advanced prehospital care, showed no improved outcome in comparison
      with a group homogeneous but for a lower level of prehospital care. METHODS: A
      retrospective registration of the early in-hospital arterial carbon dioxide
      tension of the patients intubated and ventilated on scene. Patients were excluded
      if the arterial carbon dioxide tension did not reflect prehospital ventilation or
      its alteration might have been intentional or unavoidable. RESULTS: Arterial
      carbon dioxide tension was normal (35-45 mmHg) in only six of the 16 suitable
      cases (37.5%), was elevated (>45 mmHg) in three cases (18.75%), low (25-35 mmHg)
      in five cases (31.25%), and extremely low (<25 mmHg) in two cases (12.5%).
      CONCLUSION: Potentially dangerous alterations in capnia occurred in the majority
      of patients analysed. The possible consequences and causes are discussed. Further
      studies are needed to assess the consequences of any deviation from ideal
      standards, and to set realistic standards of arterial carbon dioxide tension
      control during prehospital ventilation.

PMID- 14676503
TI  - Factors and circumstances related to complaints in emergency medical dispatching
      in Sweden: an exploratory study.
AB  - There are 20 SOS Alarm emergency dispatch centres in Sweden, and from these
      centres approximately one million ambulances are dispatched each year. The aim of
      the study was to explore factors and circumstances that contributed to
      misjudgements or filed complaints in emergency medical dispatching filed at the
      Patient Advisory Committees (n=24), the Swedish National Board of Health and
      Welfare (n=20) and the Medical Responsibility Board (n=10). This is a
      retrospective study of all decisions on complaints made between 1991 and 2000,
      and the data were analysed in two phases. In the first phase, categories of cause
      were revealed, and in the second phase, factors and circumstances were identified
      that related to misjudgements or filed complaints. The findings show that in
      nearly half (23/54) of the complaints, the assessments were stated as been made
      on the basis of second-hand consultations, e.g. the SOS operators had not spoken
      directly to the ill person. In 19 out of 21 complaints dealing with the decision
      making process, the assessments were made on second-hand information. Second-hand
      information may constitute an aggravating circumstance in assessing the urgency
      of the care needed on the telephone. The findings suggest that the call receivers
      should be more cautious when undertaking assessments on the basis of information
      provided by a third person.

PMID- 14676504
TI  - Ambulance paramedic activities in North Ayrshire: a five-year review.
AB  - BACKGROUND: Ambulance paramedics have been practising in North Ayrshire for some
      time. The aim of this study was to determine the range and number of procedures
      that are undertaken by paramedics, and whether they are performed in accordance
      with standard operating procedures. METHODS: A five-year prospective
      observational study of patients attended by paramedics in a mixed urban/rural
      area of south-west Scotland. Data were collected on all procedures undertaken in
      the prehospital arena. A single investigator decided whether each procedure was
      performed in accordance with standard operating procedures in the light of
      available information. RESULTS: Data on 6600 patients were available, a mean of
      42 patients per paramedic per year. Oxygen administration increased significantly
      and the number of occasions when excess time was spent on scene decreased
      significantly during the study. Paramedics treated significantly fewer patients
      requiring intravenous cannulation, intubation, defibrillation and cardiopulmonary
      resuscitation in year 5 compared with year 1. Paramedics administered drugs in
      accordance with standard operating procedures in almost all cases. CONCLUSION:
      Paramedic exposure to extended skills is low in this region, leading to concerns
      about advanced skills retention. Paramedics can administer drugs appropriately
      according to protocol. Increasing paramedic experience, possibly augmented by
      feedback via audit, may be influencing paramedic decision making.

PMID- 14676505
TI  - Factors that influence emergency department doctors' assessment of suicide risk
      in deliberate self-harm patients.
AB  - OBJECTIVES: To determine the patient factors influencing UK Emergency Department
      doctors' assessment of suicide risk. To establish whether immediate clinical
      management is consistent with perceived risk. METHODS: The Manchester and Salford
      Self-Harm project is a multi-centre deliberate self-harm monitoring study. Data
      collected were used to analyse risk assessments made by Emergency Department
      doctors between September 1997 and August 1999. We used univariate and logistic
      regression analyses to determine the factors Emergency Department doctors used to
      make suicide risk assessments. RESULTS: A total of 3220 deliberate self-harm
      assessment forms were completed in two years by Emergency Department doctors;
      2922 (91%) included a clinical assessment of risk; 28 out of 48 variables were
      associated with perceived suicide risk. Multiple logistic regression analyses
      showed that current mental state, high suicidal intent (including medical
      seriousness of attempt), and male sex were the most important independent
      predictors of suicide risk. Being referred to psychiatric services directly from
      the Emergency Department or to surgical/medical services was also strongly
      associated with a perceived high risk. CONCLUSION: In contrast to the negative
      findings of previous research, we found that Emergency Department doctors were
      influenced by key risk factors for suicide in their assessment of deliberate self
      harm patients. Emergency Department doctors' assessments reflected the immediate
      risk of suicide, indicated by factors such as current mental state and strong
      suicidal intent. Background risk factors such as social adversity and psychiatric
      history were less influential. We would recommend that training for emergency
      doctors should emphasize the importance of both immediate and background risk
      factors.

PMID- 14676506
TI  - Wheezing in patients with acute pulmonary embolism with and without previous
      cardiopulmonary disease.
AB  - BACKGROUND: Wheezing is a little known but possible presentation feature of acute
      pulmonary embolism. PATIENTS AND METHODS: A retrospective review of the records
      of 154 consecutive patients with acute pulmonary embolism, who survived long
      enough for diagnostic evaluation. RESULTS: Fourteen patients with acute pulmonary
      embolism (9.1%) had wheezing at presentation. Wheezing was more frequent in
      patients with previous cardiopulmonary disease than in those without previous
      cardiopulmonary disease, although this did not reach statistical significance
      (13.5 versus 6.9%; P=0.17). Dyspnoea, cough and respiratory failure were more
      frequent with statistical significance in our patients with wheezing than in
      those without wheezing. The hospital mortality rate was similar in both groups.
      CONCLUSION: Wheezing in acute pulmonary embolism may be more frequent in patients
      with previous cardiopulmonary disease. However, wheezing also occurs in patients
      with acute pulmonary embolism without previous cardiopulmonary disease. Wheezing
      may be a sign of severity in acute pulmonary embolism.

PMID- 14676507
TI  - Upper gastrointestinal haemorrhage in Emergency Departments in France: causes and
      management.
AB  - OBJECTIVES: Little is known about the epidemiology of acute upper
      gastrointestinal haemorrhage hospitalized in Emergency Departments. Most of the
      studies concerning digestive bleeding have been carried out by Gastroenterology
      Departments. This multicentre study included consecutive patients with acute
      upper gastrointestinal haemorrhage hospitalized after an initial management at
      Emergency Departments in France, to describe the initial medical management and
      to determine the causes of acute upper gastrointestinal haemorrhage. We also
      studied the relationship between the use of non-steroidal anti-inflammatory drugs
      or aspirin and the occurrence of an acute upper gastrointestinal haemorrhage by a
      case-control comparison. RESULTS: A total of 180 patients (112 men, 59+/-18
      years) were included during 23 days, and 353 controls (222 men, 57+/-13 years)
      were selected at the same time. The delay between the first clinical signs of
      acute upper gastrointestinal haemorrhage and arrival at the Emergency Department
      was 33+/-42 h, and endoscopy was performed 14+/-16 h after admission to the
      Emergency Department. Sixty-six percent of patients with cirrhosis could benefit
      from a specific vasoactive treatment. Endoscopy was performed in 160 patients.
      Bleeding was caused by ulcers and gastritis in 88 patients (49%) and portal
      hypertension in 59 (32%). The relationship between the use of non-steroidal anti
      inflammatory drugs or aspirin and acute upper gastrointestinal haemorrhage was
      confirmed, odds ratio, (OR) 1.69 [95% confidence interval (CI) 1.15-2.33], but
      not among cirrhotic patients, odds ratio 1.12 (95% CI 0.65-1.86). CONCLUSION:
      Hospitalized acute upper gastrointestinal haemorrhage in Emergency Departments in
      France is more often caused by cirrhosis than in other countries. Decreasing the
      delay between the first signs of bleeding and arrival at the Emergency Department
      is the main challenge in the management of acute upper gastrointestinal
      haemorrhage.

PMID- 14676508
TI  - The role of the emergency medicine resident using the Alvarado score in the
      diagnosis of acute appendicitis compared with the general surgery resident.
AB  - PURPOSE: To compare the accuracy of diagnosing appendicitis between emergency
      medicine residents using the Alvarado score and general surgery residents using
      ultrasonography and their clinical provision. METHODS: A total of 358 patients
      (192 men and 166 women) were admitted to the emergency service with suspected
      appendicitis. Each patient was evaluated by an emergency medicine resident and
      then by a general surgeon independently. Age, sex, operational data, diagnosis,
      and the Alvarado scores were measured. RESULTS: The sensitivity and specificity
      of the Alvarado score were 95.4% (95% confidence interval 91-99%) and 45.7% (95%
      confidence interval 37.4-54%), respectively. There was a significant difference
      between the sexes in the predictive values of a positive test (P=0.045) and a
      negative test (P=0.02). There was no statistical difference between the emergency
      medicine residents and general surgery residents in terms of positive and
      negative predicitive values (P>0.05 each). CONCLUSION: There was no statistical
      difference between the emergency medicine residents using the Alvarado score and
      the general surgery residents in terms of suspecting the diagnosis of
      appendicitis.

PMID- 14676509
TI  - Medical problems related to recreational drug use at nocturnal dance parties.
AB  - During 'I love techno' (edition 2001), an indoor rave party attended by 37 000
      people, data about medical problems (especially drug-related problems) were
      collected. To place these data in a wider perspective, a similar registration was
      done during 'De Nacht', a traditional New Year's Eve dance party held at the same
      location and attended by 12 000 people. Furthermore, a prospective study on the
      time course of the level of consciousness (Glasgow Coma Score) and blood
      concentrations of illicit drugs, especially gamma-hydroxybutyrate was set up. The
      results revealed that during 'I love techno' the incidence of medical problems
      was high (66.5/10 000 attendees), but not higher than during 'De Nacht' (70.0/10
      000 attendees). At 'I love techno', however, mainly illicit drugs were used, more
      frequently leading to severe drug-related medical problems. The observations in
      patients with a drug-related medical problem who had taken gamma-hydroxybutyrate
      showed that for a given level of consciousness the gamma-hydroxybutyrate
      concentrations may show important differences, that the transition from coma
      (Glasgow Coma Score < or =7) to full recovery (Glasgow Coma Score 15) takes only
      30-60 min (and only a small decrease in gamma-hydroxybutyrate concentrations),
      and that the time it takes before a comatose patient reaches the above-mentioned
      'transition area' may be a few hours.

PMID- 14676510
TI  - 'Ecstasy' intoxication: life-threatening manifestations and resuscitative
      measures in the intensive care setting.
AB  - OBJECTIVE: The ingestion of 3,4-methylenedioxymethamphetamine ('ecstasy') can
      cause severe neurological impairment and multi-system damage. We describe the
      potentially life-threatening clinical features and the management of intoxication
      by this psychedelic drug in patients transferred from emergency services to the
      intensive care area. METHODS: We conducted a retrospective analysis of 'ecstasy'
      intoxicated patients admitted to a municipal hospital during a three-month
      period. RESULTS: Of the 32 patients brought to the emergency services, three
      (9.3%; mean age 21+/-2 years) were transferred to the intensive care area in a
      comatose state associated with seizures after ingesting one to three tablets of
      150 mg 3,4-methylenedioxymethamphetamine. All required artificial ventilation and
      none responded to painful stimuli. The brain computed tomography scan and lumbar
      puncture results were normal. The main clinical manifestations were hyponatremia,
      high fever, rhabdomyolysis, dehydration and metabolic acidosis accompanied by
      impaired liver and renal functions. All three patients regained consciousness
      after 2.1+/-0.8 days of system-oriented supportive care and were discharged for
      further surveillance in medical wards after 4.3+/-2.1 days. CONCLUSION: The
      increase in life-threatening episodes of 3,4-methylenedioxymethamphetamine
      intoxication that mandate admission, treatment and close surveillance in an
      intensive care milieu make it incumbent to establish appropriate management
      protocols for minimizing immediate mortality and late morbidity.

PMID- 14676511
TI  - Insured versus uninsured patients in the emergency room: is there a difference?
AB  - OBJECTIVE: To define the differences in emergency room usage patterns between
      patients with and without medical insurance coverage. METHODS: A retrospective
      analysis of the database of 34 642 consecutive patient visits to an urban
      hospital emergency room over a period of 509 days. Arrival times and admission
      rates were compared for insured and uninsured patients. RESULTS: A total of 46.8%
      of insured patients arrived at night or during the weekend versus 51.7% of the
      uninsured. Slightly more insured patients were admitted (18.6 versus 15.4%), both
      after their visit during the daytime (20.6 versus 17.1%) and outside daytime
      hours (16.3 versus 13.8%). The uninsured population was younger. CONCLUSION:
      Uninsured patients arrived more frequently during weekends and at night than
      insured patients. They were on average less likely to be admitted to the
      hospital. Demographic differences between both groups seemed to play an important
      role in the admission rate. Despite differences in emergency room usage patterns,
      it cannot be concluded that either group used the emergency room in excess of the
      other.

PMID- 14676512
TI  - Emergency medicine in the Netherlands, the necessity for changing the system:
      results from two questionnaires.
AB  - OBJECTIVE: To obtain information about patient, staff and organization
      characteristics of Emergency Departments in the Netherlands, and evaluate the
      changes between 1996 and 1999. METHODS: The heads of the Emergency Departments of
      all hospitals in the Netherlands were sent a questionnaire concerning patient,
      staff, and organization characteristics, as well as questions about intended
      future developments. The results were compared with data obtained from a
      comparable questionnaire in 1996. RESULTS: In the Netherlands, 113 hospitals
      (113/126) have an Emergency Department; 105/113 returned the questionnaire (93%).
      Ninety-two percent of the hospitals reported an increase in annual Emergency
      Department census and in the number of self-referred patients. The number of
      Emergency Departments staffed by only surgical residents decreased (52% in 1996
      versus 41% in 1999), whereas the number of hospitals employing emergency
      physicians increased (24% in 1996 versus 45% in 1999). In 92% of the hospitals,
      nurses who work in the Emergency Department receive specific training. For
      emergency physicians, a specific training programme is not available, and in fact
      30% of the physicians did not have any specific emergency medicine training.
      Therefore, none of the emergency physicians were fully trained in emergency
      medicine. According to 88% of all responders, there is a future for emergency
      medicine as an independent speciality in the Netherlands, and 35% of all
      hospitals intend to initiate a training programme for emergency physicians in the
      future. CONCLUSION: Almost all hospitals in the Netherlands reported an increase
      in the number of patients visiting the Emergency Department, especially in the
      number of self-referred patients. A majority of the Emergency Departments are now
      staffed by emergency physicians instead of surgical residents. Developing
      specific training programmes for emergency physicians should be a priority for
      the Netherlands in the future.

PMID- 14676513
TI  - Cardiovascular collapse after amiodarone administration in neonatal
      supraventicular tachycardia.
AB  - Amiodarone is recommended by the International Liaison Committee on Resuscitation
      and has been adapted by the Resuscitation Council (UK) and the Advanced Life
      Support Group for use in paediatric advanced life support and advanced paediatric
      life support for the treatment of refractory supraventricular tachycardia. The
      International Liaison Committee on Resuscitation has stated that resuscitation
      guidelines should be evidence based. We present a case report of a
      cardiovascularly stable infant with supraventricular tachycardia who had a
      variety of arrthymias requiring cardiopulmonary resucitation for a prolonged
      period of time after loading with intravenous amiodarone. We believe that this
      report, together with other evidence, may suggest caution with the use of
      amiodarone.

PMID- 14676514
TI  - A severe methaemoglobinemia induced by nitrates: a case report.
AB  - Methaemoglobinemia is a disorder in which the haemoglobin molecule is
      functionally altered and prevented from carrying oxygen. A variety of aetiologies
      including genetic, dietary, idiopathic and toxicological sources may cause
      methaemoglobinemia. Symptoms vary from mild headache to coma or death, and may
      not correlate with measured methaemoglobin concentrations. Patients with
      methaemoglobinemia appear deeply cyanotic, but are unresponsive to standard
      oxygen therapy. It is essential for the clinician to recognize the problem
      rapidly in patients without hypoxia by analysing their arterial blood gas.
      Methaemoglobin interferes with the accuracy of pulse oximetry. The antidote is
      methylene blue. We report a very unusual and dramatic case of methaemoglobinemia.
      A 23-year-old girl who arrived in the emergency department in a state of
      confusion with intense cyanosis. The night before she had drunk water with ice
      defiled by ammonium nitrate, poured from a broken pack of instant ice. The
      absence of improvement after the administration of oxygen and the 'chocolate
      brown' colour of the arterial blood gave us the most important clue in suspecting
      the diagnosis of methaemoglobinemia.

PMID- 14676515
TI  - Bradycardia related to hypoglycaemia.
AB  - Alterations in blood glucose levels are known to be involved in electrocardiogram
      changes. Various types of arrhythmias have been reported. We present here the
      case of an 81-year-old woman presenting with transient atrial fibrillation while
      being treated for hypoglycaemia with dextrose infusion, and finally developing a
      sinus rhythm. The presence of alterations in glucose blood levels should always
      be considered as a potential cause of transient atrial fibrillation.

PMID- 14676516
TI  - A laryngeal foreign body misdiagnosed as asthma bronchiale.
AB  - Laryngotracheal foreign bodies, although less common than bronchial foreign
      bodies, are potentially more dangerous. We report a 10-year-old girl with Down
      syndrome with asthma bronchiale symptoms, which was later found to be the result
      of a thin bone lamella impacted in her larynx. There was no clear history of
      foreign body aspiration. She was treated with the initial diagnosis of asthma
      bronchiale. It took a month before the final diagnosis was made. The foreign body
      was removed via direct laryngoscopy. It was a white and thin bone lamella with
      sharp edges, measuring 28 x 19 x 2 mm. We thought the case was worth presenting
      because of its rare location, the size of the foreign body, and the long duration
      before the final diagnosis was made.

PMID- 14676517
TI  - Hollow visceral injury after blunt lower thoracic and abdominal trauma.
AB  - The early diagnosis of hollow viscous injury after blunt abdominal trauma remains
      a challenge for physicians in the Emergency Department, although the early
      diagnosis of hollow viscous injury decreases morbidity and mortality. After a
      description of two cases of hollow viscous injury after blunt abdominal trauma, a
      literature review is performed concerning the indications and limitations of
      diagnostic imaging modalities. Focused abdominal sonography for trauma, computed
      tomography scan and diagnostic peritoneal lavage are described. On the basis of
      the review a proposal for maximal diagnostic accuracy is made.

PMID- 14676518
TI  - Acute communicating haematocele: unusual presentation after blunt abdominal
      trauma without solid organ injury.
AB  - Haematocele is an unusual scrotal disorder in children, and is generally
      associated with direct trauma to the inguinoscrotal region. A 6-year-old boy with
      acute communicating haematocele who had a history of blunt abdominal trauma one
      week earlier is presented. Interestingly, no solid organ injury was detected on
      his previous admission for abdominal trauma, nor there was a history of
      hydrocele.

PMID- 14676519
TI  - Acute post-traumatic tension gastrothorax, a tension pneumothorax-like injury.
AB  - Diaphragmatic rupture is an uncommon and frequently missed complication in blunt
      thoraco-abdominal trauma. Symptoms usually become apparent in a delayed phase, up
      to years after the trauma. An acute presentation is extremely rare and acute
      tension gastrothorax in which trapping of air in the intrathoracic stomach causes
      mediastinal shift and lung compression, as in tension pneumothorax, is
      exceptional. We only found two cases in the literature. We present here two other
      cases from our practice, with a review on the literature on post-traumatic
      diaphragmatic hernias.

PMID- 14676520
TI  - Irreducible dislocation of the interphalangeal joint of the thumb: a case report.
AB  - A case of open irreducible dislocation of the interphalangeal joint of the thumb
      with interposed flexor pollicis longus tendon and palmar plate with sesamoid bone
      is described.

PMID- 14676521
TI  - Defibrination and systemic bleeding caused by an imported African snakebite.
AB  - A 55-year-old man was referred from Burkina Fasso for coagulation disorders with
      severe spontaneous systemic bleeding. He had been bitten six days before by a
      snake that could not be definitely identified. No specific treatment had been
      started in Africa. The patient was admitted with severe anaemia, incoagulable
      blood with undetectable fibrinogen. Multiple haematomas in the chest and abdomen
      were found at computed tomography. Blood transfusions and the administration of
      fresh frozen plasma and fibrinogen did not result in any clinical or biological
      improvement. The clinical course was dramatically reversed after the infusion of
      two vials of Pasteur polyspecific antivenom (Echis-Bitis-Naja). According to the
      geographical distribution of this snake species, it seems very likely that the
      snakebite was caused by Echis ocellatus. Even given with delay, the antivenom was
      effective and well tolerated.

PMID- 14676522
TI  - Acute confusion and blindness from quinine toxicity.
AB  - Quinine is widely used for nocturnal leg cramps, despite limited evidence of its
      clinical efficacy in this condition. Accidental overdose is associated with
      serious ocular complications and can potentially be fatal. We report the case of
      a 57-year-old man who presented with acute confusion and bilateral blindness
      after consuming approximately 7.2 g quinine sulphate along with an unknown
      quantity of alcohol. He was treated with general supportive measures and
      nitrates, with an apparent initial recovery, but visual field defects persisted.
      This case highlights the potential toxic effects of quinine, the dangers of its
      bulk prescription, and the lack of strict guidelines with regard to its
      prescription. We suggest that restricted prescribing for leg cramps, better
      patient education about the toxic nature of the drug, and clear labelling of this
      hazard on the dispensing bottles might lead to a reduction in the cases of
      quinine poisoning.

PMID- 14676523
TI  - A false positive arrhythmia on electrocardiogram induced by a cell phone.

PMID- 14676524
TI  - Preventive treatment for re-expansion pulmonary oedema.
AB  - Re-expansion pulmonary oedema is a rare but life-threatening condition that may
      complicate the treatment of pneumothorax. Current opinions vary regarding how
      this condition can be prevented. The concepts behind these various theories are
      discussed with an emphasis on applying available evidence and expert guidelines
      to practice.

PMID- 14676525
TI  - Complications and outcomes of open pediatric forearm fractures.
AB  - Few reports have documented the complications and outcomes of open pediatric
      forearm fractures. The authors completed of all patients (1987-1999) with open
      forearm fractures. Sixty-five patients with 65 injured extremities were
      identified, with an average age of 10.3 years. Fifty-two open fractures were
      grade I, 12 were grade II, and 1 was grade IIIA. Implants stabilized 40
      extremities (62%), which improved alignment but not outcome. Forearms initially
      stabilized with implants did not undergo additional realignment procedures (0%),
      compared with 18.5% of forearms without stabilization. Eleven patients (16.9%)
      experienced complications. Overall, 47 (72%) were classified as having excellent
      results, 11 (17%) as good, and 7 (11%) as fair. Open pediatric forearm fractures
      have a high percentage of excellent and good outcomes. Early, thorough surgical
      debridement produces a low frequency of deep infections, and bony stabilization
      can be a safe technique, permitting more anatomic alignment and preventing the
      need for reoperation due to malalignment.

PMID- 14676526
TI  - Percutaneous transphyseal intramedullary Kirschner wire pinning: a safe and
      effective procedure for treatment of displaced diaphyseal forearm fracture in
      children.
AB  - Percutaneous transphyseal intramedullary Kirschner wire (K-wire) fixation was
      performed for diaphyseal fracture of the forearm in 84 children. In 60 patients
      (71%) closed reduction was performed, while in the remaining 24 (29%) closed
      reduction was supplemented with a mini-open reduction The K-wire was inserted
      transphyseally through the radial styloid or the Lister tubercle for the radius,
      and through the tip of the olecranon for the ulna. With an average follow-up of
      70 months and a minimum follow-up of 2 years, all the patients reviewed were
      found to have good functional results; none had nonunion, deep infection, or
      premature physeal closure. Moreover, initial preoperative translation of the
      fracture of more than 100% displacement was found to be associated with a
      significantly higher chance of requiring a mini-open reduction. The authors
      concluded that percutaneous transphyseal intramedullary K-wire pining for forearm
      diaphyseal fracture in children is a convenient, effective, and safe operation,
      without any deleterious effects on subsequent growth of the distal radius.

PMID- 14676527
TI  - Closed reduction and percutaneous stabilization of pediatric T-condylar fractures
      of the humerus.
AB  - T-condylar fractures of the humerus are a rare fracture pattern in children. The
      usual recommendation is to treat them with open reduction and internal fixation,
      in accordance to the usual practice in adult fracture patterns. This involves
      extensive surgical approach to the elbow to allow anatomic reduction and
      placement of hardware for rigid fixation. The authors present a technique of
      closed reduction of the intra-articular component of the T-condylar fracture that
      is stabilized with partially threaded pins that afford interfragmentary
      compression, followed by the use of two elastic titanium intramedullary nails to
      stabilize the supracondylar component of the fracture as well. Two adolescents
      (12 and 14 years of age) with a T-condylar elbow fracture were treated with the
      described technique. Both fractures healed without complications. Hardware was
      removed in the outpatient clinic after 4 weeks, and both patients returned to
      sports with full range of elbow motion 6 weeks postoperatively.

PMID- 14676528
TI  - Is external fixation in pediatric femoral fractures a risk factor for refracture?
AB  - The aim of this study was to investigate whether external fixation is a risk
      factor for refracture by comparing the outcomes of children who received three
      different forms of treatment of femoral fractures. One hundred ninety-two
      patients treated for femoral fracture between 1990 and 1999 who underwent final
      examination were assessed. One hundred were treated with hip spica casting after
      traction, 57 with closed reduction and external fixation, and 35 with open
      reduction and external fixation. Morbidity results such as time to union, length
      of hospital stay, refracture, and wire site infection were statistically
      evaluated. Patients undergoing open reduction had a greater time to union and
      length of hospital stay and a higher refracture rate. The difference was
      statistically significant. Wire site infection occurred in all three groups;
      there was no statistically significant difference between groups. The authors
      concluded that external fixation is not a risk factor for refracture in the
      treatment of pediatric closed femoral diaphyseal fractures, and that it may be
      used with ease in clinics with shortages of personnel and space.

PMID- 14676529
TI  - Progressive forearm lengthening with an intramedullary guidewire in children:
      report of 10 cases.
AB  - Indications for forearm lengthening are rare. Between 1994 and 1999, 10 forearm
      lengthenings were performed in seven children for functional reasons and/or
      esthetic discomfort. Only one of the two forearm bones was involved in the
      procedure in all cases. The technique consisted of a transverse osteotomy and
      progressive distraction after intramedullary nailing. When a bone axis correction
      was needed, it was performed with a substraction osteotomy in the initial
      osteotomy site. The distraction device was removed when bone healing was
      achieved. The authors noted the various complications and assessed the amount of
      elongation, bone healing, and potential bone axis deviation. Mean follow-up was
      4.5 years. Mean elongation was 30.8 mm. Four bone grafts were needed for delayed
      union. No bone axis deviation was noted. An initial axial correction osteotomy
      allows an easier lengthening procedure. Use of an intramedullary wire avoids axis
      deviation. This technique can be helpful in malformative pathologies.

PMID- 14676530
TI  - Reliability of radiographic assessment of distraction osteogenesis site.
AB  - The presence of three of four continuous cortices on anteroposterior and lateral
      radiographs has been stated to be an indication of bony healing of distraction
      osteogenesis. In this study the authors assessed the level of agreement of
      radiographic assessment of bony union. Forty-two lower extremity radiographs of
      consolidating distraction gaps were reviewed by nine examiners on two occasions
      for number of cortices and whether fixator removal was indicated. For number of
      cortices, the kappa coefficients for interobserver and intraobserver variability
      were 0.127 and 0.290. For fixator removal, the interobserver and intraobserver
      coefficients were 0.352 and 0.461. Variation in assessment of number of cortices
      was slightly better than chance, indicating an inadequate measure of healing. The
      clinicians used radiographic criteria other than three of four cortices for
      fixator removal. The decision to remove an external fixation device based on
      radiographic assessment alone resulted in intraobserver and interobserver
      variability moderately above chance.

PMID- 14676531
TI  - Spinal deformity following selective dorsal rhizotomy.
AB  - The authors performed a review of 79 patients treated by selective dorsal
      rhizotomy with laminoplasty, 78 of whom were ambulatory, to determine the
      prevalence of spinal deformities. The mean radiographic follow-up was 4.2 years,
      the mean clinical follow-up 5.8 years. Scoliosis (11 degrees -24 degrees ) was
      identified in 13 children, none of whom had a preexisting deformity. There were
      no significant differences between preoperative and follow-up thoracic kyphosis
      or lumbar lordosis, although there was a significant difference in lumbar
      lordosis between sitting and standing radiographs. No progressive or rigid
      hyperlordotic deformities were observed in the lumbar spine. Spondylolisthesis
      was identified in nine children (12%) (8/9 grade I), and one patient required an
      arthrodesis for pain. Spondylolisthesis was correlated with greater lumbar
      lordosis, stronger hip abductors, and increased popliteal femoral angles
      preoperatively, and with stronger hip flexors postoperatively. Back pain was
      identified in 4 of the 79 patients at last follow-up, 2 of whom had
      spondylolisthesis. As some cases of spondylolisthesis will remain asymptomatic,
      periodic radiographic follow-up is recommended.

PMID- 14676532
TI  - Kyphectomy in children with myelomeningocele: a long-term outcome study.
AB  - Twenty-four children with myelomeningocele and a kyphotic deformity treated by
      surgical correction between 1980 and 1994 were reviewed. Different techniques of
      instrumentation and spinal fusion were used. The mean age at surgery was 9.5
      years. The mean kyphotic angle was 121 degrees preoperatively, 50 degrees
      postoperatively, and 57 degrees at final follow-up. The postoperative
      complication rate was high. Delayed wound healing and late skin breakdown with
      exposure of instrumentation were common problems. Further surgery to remove
      protruding hardware was necessary in 18 patients. Long posterior instrumentation
      with fixation to the pelvis had significantly better stability on follow-up than
      other methods. Despite the prolonged postoperative morbidity in the majority of
      the study group, the long-term clinical and radiologic outcome at a mean follow
      up of 10 years was excellent.

PMID- 14676533
TI  - Comprehensive treatment of ambulatory children with cerebral palsy: an outcome
      assessment.
AB  - A retrospective study was used to evaluate the outcome of treatment of 135
      ambulatory children with cerebral palsy. Diplegic subjects were selected from the
      existing database at the Gillette Children's Specialty Healthcare Motion Analysis
      Laboratory. All subjects had undergone gait analysis before and after
      intervention, which included orthopaedic surgery, selective dorsal rhizotomy, or
      both treatments. Outcome was based on gait pathology, gait efficiency, functional
      walking ability, and higher-level functional skills. Gait pathology was assessed
      using 16 clinically relevant kinematic parameters. Gait efficiency was assessed
      with steady-state oxygen consumption. Walking ability and higher-level functional
      skills were based on patient report surveys. Improvements were seen in all
      outcome measures. A significant majority of subjects (79%) improved on a
      predominance of outcome measures; only 7% of subjects worsened. Within the
      restrictions of this study design, the results indicate that surgical
      intervention, guided by preoperative gait analysis, is effective and safe for
      children with cerebral palsy.

PMID- 14676534
TI  - Comparison of parents' and caregivers' satisfaction after spinal fusion in
      children with cerebral palsy.
AB  - The purpose of this study was to delineate parents' and professional caretakers'
      satisfaction after spinal fusion in children with spasticity and to determine
      differences in their perceptions. A questionnaire assessing patients' functional
      improvement after spinal arthrodesis for correcting scoliosis was addressed to
      190 parents. An expanded questionnaire was also addressed to 122 educators and
      therapists working in the care of children with cerebral palsy. Caretakers did
      not recognize effects of the scoliotic deformity on patients' head control, hand
      use, and feeding ability. Most of parents and caregivers reported a very positive
      impact of the surgery on patients' overall function, quality of life, and ease of
      care. Parents had more appreciation of the benefits in the children's appearance,
      whereas educators and therapists acknowledged more improvement in gross and oral
      motor function. Considering that the benefits from scoliosis correction clearly
      outweigh the increased risk of surgical complications, most parents (95.8%) and
      caretakers (84.3%) would recommend spine surgery.

PMID- 14676535
TI  - Predictive value of the Duncan-Ely test in distal rectus femoris transfer.
AB  - Fifty-six patients who underwent 94 distal rectus femoris transfers and pre- and
      postoperative gait analyses were retrospectively reviewed. The patients were
      divided into three groups based on pre- and postoperative Duncan-Ely tests. Group
      A (34 limbs) had positive tests both before and after surgery. Group B (46 limbs)
      had positive tests before surgery and negative tests after surgery. Group C (13
      limbs) had negative tests both before and after surgery. One limb had a negative
      test before surgery and a positive test after surgery and was not included in any
      group. Knee arc increased significantly in both groups with positive preoperative
      Duncan-Ely tests (groups A and B), but not in the group with negative
      preoperative tests (group C). The timing of peak knee flexion in swing improved
      in all groups, but the change was smaller and not statistically significant in
      the group with negative preoperative tests (group C). The findings of the current
      study indicate that the Duncan-Ely test may be a helpful predictor of outcome in
      children for whom distal rectus femoris transfer is being considered. Caution
      should be exercised when patients have weak quadriceps and a negative Duncan-Ely
      test before surgery, particularly when concurrent calf lengthening procedures are
      planned.

PMID- 14676536
TI  - Treatment for idiopathic toe-walking: results at skeletal maturity.
AB  - Thirteen skeletally mature subjects who had been treated as children for
      idiopathic toe-walking underwent gait analysis and calf muscle strength testing
      at an average of 10.8 years from the last intervention. Six had had serial
      casting only; seven had had either a percutaneous tendo Achilles lengthening or a
      Baker's gastroc-soleus lengthening. Sagittal plane kinematics at the ankle was
      altered in 12 of the 13 subjects, but the changes were detectable visually in
      only 3 subjects. One subject had increased ankle plantarflexion at initial
      contact, but the other 12 subjects had a normal first rocker. Peak ankle
      dorsiflexion in stance averaged only 9 degrees, and 11 of the subjects had a peak
      ankle dorsiflexion in stance greater than 2 standard deviations below normative
      values. Ankle dorsiflexion was also restricted on passive measures, but there was
      no correlation between ankle dorsiflexion non-weight-bearing and in gait.
      Inversion of second rocker was seen in two subjects with peak ankle dorsiflexion
      in stance occurring before 25% of the gait cycle. Power generation by the calf
      during a single heel-rise test was variable between subjects but within normative
      values compared with controls. The authors conclude that most subjects showed
      persistent changes in ankle kinematics and kinetics despite treatment but that
      this was not detectable visually in most subjects.

PMID- 14676537
TI  - Gait analysis of stapling for genu valgum.
AB  - Many authors have advocated stapling or epiphysiodesis of the distal medial femur
      as a means of correcting genu valgum. However, in the literature, aside from
      clinical improvement (appearance, pain, function), objective evidence of kinetic
      and kinematic improvement is lacking. Therefore, the authors undertook a
      prospective gait analysis evaluation of a series of patients treated for genu
      valgum, comparing pre- and postsurgical measurements to document the benefits of
      normalizing the mechanical axis. These results indicate that after surgery knee
      and hip angles and knee moments were returned to within the normal range for a
      similarly aged control group.

PMID- 14676538
TI  - Variability of the metaphyseal-diaphyseal angle in tibia vara: a comparison of
      two methods.
AB  - Although Levine and Drennan described the metaphyseal-diaphyseal angle (MDA) in
      tibia vara using the lateral border of the tibial cortex, there is a lack of
      uniformity in the literature. The authors measured the MDA using both the lateral
      border and the center of the tibial shaft in 132 knees (66 patients) with bowleg
      deformity and examined whether there is a significant difference between these
      two measurements. At angles < or =11 degrees there was significant variance
      between the two methods. At angles >11 degrees, there was excellent correlation
      between the two methods and no statistical difference between the two methods.
      The authors conclude that either method of defining the longitudinal axis is
      acceptable to measure the MDA for the diagnosis and monitoring of tibia vara.

PMID- 14676539
TI  - Discoid lateral meniscus: prevalence of peripheral rim instability.
AB  - The purpose of this study was to determine the prevalence of peripheral rim
      instability in discoid lateral meniscus. A consecutive series of 112 patients
      (128 knees) (mean age 10.0 years [range 1 month to 22 years]) who underwent
      arthroscopic evaluation and treatment of a discoid lateral meniscus between 1993
      and 2001 was reviewed. Of those discoid menisci classified intraoperatively (n =
      87), 62.1% (n = 54) were complete discoid lateral menisci and 37.9% (n = 33) were
      incomplete discoid lateral menisci. An associated meniscal tear was present in
      69.5% (n = 89) of all knees studied. Overall, 28.1% (n = 36) of discoid lateral
      menisci had peripheral rim instability: 47.2% (n = 17) were unstable at the
      anterior-third peripheral attachment, 11.1% (n = 4) at the middle-third
      peripheral attachment, and 38.9% (n = 14) at the posterior-third peripheral
      attachment. Thirty-one of the 36 unstable discoid menisci underwent repair of the
      peripheral meniscal rim attachment. One patient underwent a complete, open
      meniscectomy. Peripheral rim instability was significantly more common in
      complete discoid lateral menisci (38.9% vs. 18.2%; P = 0.043) and in younger
      patients (8.2 vs. 10.7 years; P = 0.002). The frequency of peripheral instability
      mandates a thorough assessment of meniscal stability at all peripheral
      attachments during the arthroscopic evaluation and treatment of discoid lateral
      meniscus, particularly in complete variants and in younger children.

PMID- 14676540
TI  - Arthropathy of the knee joint caused by synovial hemangioma.
AB  - Degenerative changes resembling hemophilic arthropathy may be a complication of
      synovial hemangioma in the knee. It is thought that arthropathy is caused by
      repeated bleeding episodes similar to the joint disease in hemophilia. Four
      children aged 4 to 9 years at surgery were treated by anterior open synovectomy
      for intra-articular synovial hemangiomas. At open surgery the cartilage of all
      patients showed changes on the surface with yellow hematin staining in all cases,
      without ulceration in three patients but one, who showed severe degenerative
      changes at age 9 years. At 15 months follow-up the patient with severe
      degenerative changes had severely impaired flexion and mild extension deficit.
      The three others were asymptomatic at 1 to 6 years follow-up. The magnetic
      resonance images were typical and can be considered pathognomonic; however, the
      referral diagnosis included the correct diagnosis in none of them. Treatment
      should be initiated as early as possible to reduce the risk of damage to the
      cartilage. Treatment by complete open synovectomy in these four patients was
      performed without significant bleeding problems, and no recurrence was seen.

PMID- 14676541
TI  - Hemangioma of the radius associated with Kasabach-Merritt syndrome: case report
      and literature review.
AB  - The Kasabach-Merritt syndrome of consumptive coagulopathy associated with massive
      hemangiomas is a potentially life-threatening problem in patients with a
      pathologic fracture of the osseous lesion. This can result in massive bleeding
      even after minor trauma. In such patients, operative management of long bone
      hemangiomatous lesions, including percutaneous needle aspirations, may be
      contraindicated, and nonoperative management may be preferable. Kasabach-Merritt
      syndrome must be suspected in patients with large hemangiomas with associated
      bone lesions, and appropriate coagulation studies should be obtained before any
      operative management. Review of the world English literature on Kasabach-Merritt
      syndrome has revealed that the most common pathologic fractures occur in the
      vertebral bodies. An additional case report of a child with a pathologic fracture
      and deformity of his radius has been documented. Decreased hematocrit and
      fibrinogen levels associated with thrombocytopenia and a prolonged prothrombin
      time and partial thromboplastin time in association with bone hemangioma should
      alert the orthopaedist to the possibility of Kasabach-Merritt syndrome.

PMID- 14676542
TI  - Orthopaedic manifestations of Bardet-Biedl syndrome.
AB  - Bardet-Biedl syndrome is an autosomal recessive disorder poorly characterized in
      the orthopaedic literature. Classic manifestations of the syndrome include
      pigmentary retinopathy, obesity, polydactyly, hypogonadism, and mild mental
      retardation. Previous reports have implied that orthopaedic findings are due to
      an epiphyseal dysgenesis inherent to the syndrome. The purpose of this study was
      to evaluate the orthopaedic manifestations of 27 patients with this syndrome.
      Detailed medical histories and physical examinations as well as pedigree analyses
      and radiographic bone surveys were performed. Orthopaedic findings included the
      following: 17 patients had postaxial polydactyly, 4 patients had scoliosis, 2
      patients had tibia valga, 2 patients had tibia vara, and 1 patient had Legg-Calve
      Perthes. The bone survey did not reveal any additional radiographic
      abnormalities. Based on these results, Bardet-Biedl syndrome patients do not have
      epiphyseal dysgenesis; their epiphyseal manifestations are probably the result of
      their obesity.

PMID- 14676543
TI  - Musculoskeletal manifestations of Hurler syndrome: long-term follow-up after bone
      marrow transplantation.
AB  - Bone marrow transplantation (BMT) is effective in ameliorating many of the
      clinical manifestations of Hurler syndrome. However, long-term data on the
      natural history of the musculoskeletal disorders of Hurler syndrome after BMT are
      limited. The authors report the orthopaedic outcomes in seven patients with
      Hurler syndrome who were successfully engrafted between 1990 and 1999, and have
      been followed for a mean of 7.6 years since transplantation. Medical records,
      clinical examinations, and imaging studies were reviewed to assess the
      development and management of hip dysplasia, genu valgum, spine abnormalities,
      hand abnormalities, and joint range of motion. BMT does not appear to alter the
      natural history of the musculoskeletal disorders in Hurler syndrome, although
      there may be a beneficial effect on upper extremity joint mobility.

PMID- 14676544
TI  - Determination of bone age in children with cartilaginous dysplasia (multiple
      hereditary osteochondromatosis and Ollier's enchondromatosis).
AB  - Cartilaginous dysplasias (multiple hereditary osteochondromatosis [MHO] and
      Ollier's enchondromatosis [OE]) are common pediatric orthopaedic conditions. Long
      bone growth deformities commonly develop in children with MHO and OE. The timing
      of procedures frequently used to treat these deformities is often dependent upon
      the bone age. It was the purpose of this study to investigate bone ages in a
      series of 40 children with MHO and OE. There were 6 girls and 9 boys with OE, and
      9 girls and 16 boys with MHO. Each child's age, gender, race, and diagnosis were
      recorded. Hand-wrist radiographs obtained during routine evaluation of hand-wrist
      deformities or scanograms were identified, randomly numbered, and blinded
      regarding the identity and age of the child. Each radiograph was reviewed by five
      different observers at two different times separated by a minimum of 3 weeks.
      Statistical analyses were performed, looking at differences between bone and
      chronological age; inter- and intraobserver variability in bone age assessment;
      and differences by observer. The average chronological age (n = 40) was 7.8 +/-
      3.6 years, average bone age (n = 400) was 7.2 +/- 3.7 years, and average
      difference between chronological and bone age (n = 400) was 0.6 +/- 1.3 years (P
      < 10-6). Intra- and interobserver variability was +/-1.5 and +/-1.6 years. There
      were no differences between observers in the average chronological/bone age
      difference (P = 0.63). Clinicians should be aware of this average 0.6-year delay
      in bone age when planning an epiphysiodesis for limb length equalization in
      children with cartilaginous dysplasias.

PMID- 14676545
TI  - Treatment of chronic osteomyelitis in children resistant to previous therapy.
AB  - Patients admitted to the authors' institution with tibial osteomyelitis between
      1978 and 1998 were reviewed. The purpose of this study was to determine the
      incidence, etiology, treatment, and outcome in chronic pediatric tibial
      osteomyelitis. The authors describe their treatment of chronic osteomyelitis in
      children resistant to previous therapeutic modalities. Thirty patients were
      identified with a mean age of 8.5 years at diagnosis. Mean age at admission was
      9.6 years, indicating more than a 1-year duration of disease. Follow-up averaged
      2.3 years. Patients underwent 97 procedures, averaging 3.2 procedures per
      patient. Hospital stay ranged from 2 weeks to 18 months, with an average stay of
      4.7 months. Seventy-seven percent of patients were culture-positive, and 78% of
      positive cultures identified Staphylococcus aureus as the causative pathogen.
      Eighty percent of patients had a good outcome, 13% had a fair outcome, and there
      were no poor results. Patients with large tibial defects obtained good results
      with both tibiofibular synostosis and Ilizarov distraction osteogenesis. The
      authors describe the only reported group of pediatric patients successfully
      treated using Ilizarov bone transport for bony tibial defects due to
      osteomyelitis.

PMID- 14676546
TI  - Langerhans cell histiocytosis: a primary viral infection of bone? Human herpes
      virus 6 latent protein detected in lymphocytes from tissue of children.
AB  - To better understand the etiology of Langerhans cell histiocytosis (LCH), the
      authors analyzed tissue from 35 children diagnosed with LCH for the presence of
      viral proteins and DNA by immunohistochemistry (IHC) and in situ hybridization
      (ISH). Eighteen control biopsies were obtained from patients without LCH.
      Confirmatory ISH was randomly performed on four positive and two negative cases
      determined by IHC. Twenty-five (71.4%) tissue samples with LCH involvement
      stained by IHC with the 101-kDa antibody against human herpesvirus-6 (HHV-6).
      None were positive with antibodies against the p41/38 or gp110 viral proteins.
      Five (27.7%) positive control tissues demonstrated presence of the 101-kDa viral
      protein in a similar fashion. The difference in the prevalence of HHV-6 in LCH
      positive tissues (25/35) when compared with control tissues from patients without
      LCH involvement (5/18) was statistically significant. ISH confirmed the IHC in
      all six tissues tested. These findings demonstrate an association between HHV-6
      and LCH, suggesting a role for the HHV-6B in the etiology of this disease.

PMID- 14676547
TI  - Pediatric pelvic fractures.

PMID- 14676548
TI  - Acoustical technique for screening developmental dysplasia of the hip is not new.

PMID- 14676549
TI  - Wound healing complications in closed and open calcaneal fractures.
AB  - OBJECTIVES: To determine the rate of serious infection in closed and open
      calcaneal fractures that were treated with open reduction and internal fixation
      (ORIF) via an extensile lateral approach. DESIGN: Retrospective review. SETTING:
      Level 1 trauma center. PATIENTS: Two groups of patients with calcaneal fractures
      treated with ORIF via an extensile lateral approach by the senior author are
      included. The first group contained 341 closed fractures in patients injured
      during the period 1994-2000. The second group included 39 open calcaneal
      fractures in patients injured during the period 1989-2000. MAIN OUTCOME
      MEASUREMENTS: The age, sex, pre-existing medical conditions, compliance history,
      mechanism of injury, soft tissue status, presence of serious infection, and
      treatment of the infection were recorded for each patient. Data were gathered by
      review of patient records and by telephone interview when medical records were
      incomplete. The rate of serious infection in the closed and open samples was
      determined. A literature review yielded 15 reports that contained sufficient
      detail to calculate the rate of serious infection. RESULTS: Of patients, 1.8%
      with closed fractures and 7.7% with open fractures experienced serious infections
      that required intervention beyond oral antibiotics. All of these feet eventually
      healed their incisions and fractures. The calculations from data obtained from
      the literature review indicate rates of serious infection of 0-20% for closed and
      19-31% for open calcaneal fractures. CONCLUSIONS: When done correctly in
      compliant patients, ORIF for calcaneal fractures via the extensile lateral
      approach (which allows for restoration of calcaneal anatomy after substantial
      disruption) does not expose the patient to undue risk of serious infection.

PMID- 14676550
TI  - Open calcaneal fractures: results of operative treatment.
AB  - OBJECTIVE: To review our series of open calcaneal fractures compared with other
      series. DESIGN: Retrospective review. SETTING: All patients were treated at a
      single Level 1 trauma center. PATIENTS/PARTICIPANTS: We reviewed 19 consecutive
      patients, each with an open fracture of the calcaneus. Fracture morphology ranged
      from Sanders type II to type IV; associated soft tissue injuries were variable,
      ranging from Gustilo type I to type IIIC. INTERVENTION: All patients were treated
      with intravenous antibiotics, tetanus prophylaxis, and immediate and repeat
      irrigation and debridement. Definitive fracture reduction was performed at an
      average of 7 days after injury (range 0-22 days). Fixation methods included
      lateral plate and screws (11), Kirschner wires and/or screws (6), or none (2).
      MAIN OUTCOME MEASUREMENTS: AOFAS ankle-hindfoot scores, clinical examination, and
      radiographs. RESULTS: All 19 patients were available for follow-up with a
      physical examination and radiographs at an average of 26.2 months. The AOFAS
      ankle-hindfoot scores averaged 81.6 (range 58-94). Five patients required free
      tissue transfer for wound coverage. Two patients developed chronic, draining
      calcaneal osteomyelitis, for which one patient underwent a below-knee amputation.
      In our series, for the patients with Gustilo type II and type III open calcaneal
      fractures, there was an 11% complication rate with higher than expected health
      related quality-of-life indices. CONCLUSIONS: Our findings do not reflect as high
      a complication rate for open calcaneal fractures as previously reported. We
      support previous claims that definitive hardware placement at the time of initial
      irrigation and debridement probably is not warranted: Definitive fracture
      stabilization can and should wait until soft tissue coverage is fully assessed.

PMID- 14676551
TI  - Intramedullary fixation of unstable intertrochanteric hip fractures: one or two
      lag screws.
AB  - OBJECTIVE: To compare the screw sliding characteristics and biomechanical
      stability of four-part intertrochanteric hip fractures stabilized with an
      intramedullary nail using either one large-diameter lag screw (intramedullary hip
      screw [IMHS]; Smith & Nephew, Memphis, TN) or two small-diameter lag screws
      (trochanteric antegrade nail [TAN]; Smith & Nephew, Memphis, TN). DESIGN:
      Laboratory investigation using eight matched pairs of cadaveric human femurs with
      simulated, unstable intertrochanteric hip fractures. INTERVENTION: One femur of
      each matched pair was stabilized with an IMHS intramedullary nail, and the other
      was stabilized with a TAN intramedullary nail. Femurs were statically, then
      cyclically loaded on a servohydraulic materials testing machine. Finally, all
      specimens were loaded to failure. MAIN OUTCOME MEASURES: Screw sliding and
      inferior and lateral head displacements were measured for applied static loads
      from 500N to 1250N. The same measurements were obtained before and after
      cyclically loading the specimens at 1250N. Ultimate failure strength of the
      implant constructs also was determined. RESULTS: There was no significant
      difference between the TAN and IMHS in static or cyclical loading with respect to
      screw sliding or inferior and lateral head displacements. There was a
      statistically significant difference (P < 0.02) in failure strength, with the
      IMHS construct failing at an average of 2162N and the TAN construct failing at an
      average of 3238N. CONCLUSION: The two constructs showed equivalent rigidity and
      stability in all parameters assessed in elastic and cyclical tests. The TAN had a
      greater ultimate failure load.

PMID- 14676552
TI  - Anterior knee pain and thigh muscle strength after intramedullary nailing of
      tibial shaft fractures: a report of 40 consecutive cases.
AB  - OBJECTIVES: Chronic anterior knee pain is a common complication following
      intramedullary nailing of a tibial shaft fracture. The source of pain is often
      not known nor is the reason for a simultaneous decrease in thigh muscle strength.
      Anterior knee pain has also been reported following an anterior cruciate ligament
      rupture. No previous investigation has assessed whether weakness of the thigh
      muscles is associated with anterior knee pain following intramedullary nailing of
      tibial shaft fractures. DESIGN: Prospective study. SETTING: University Hospital
      of Tampere, University of Tampere. PATIENTS: Fifty consecutive patients with a
      nailed tibial shaft fracture were initially included in the study. Ten patients
      did not have isokinetic strength testing for various reasons and were eliminated
      from the study. MAIN OUTCOME MEASUREMENTS: Isokinetic muscle strength
      measurements were done in 40 patients at an average 3.2 +/- 0.4 (SD) years after
      nail insertion (1.7 +/- 0.3 years after the nail extraction). RESULTS: Twelve
      (30%) patients were painless and 28 (70%) patients had anterior knee pain at
      follow-up. With reference to the hamstrings muscles, the mean peak torque deficit
      of the injured limb (as compared with the uninjured limb) was 2 +/- 11% in the
      painless group and 11 +/- 17% in the pain group at a speed of 60 degrees /s (P =
      0.09, [95% CI for the group difference = -18% to 0%]). At a speed of 180 degrees
      /s, the corresponding deficits were -3 +/- 13% and 10 +/- 21% (P = 0.03, [95% CI
      for the group difference = -4% to -2%]). With reference to the quadriceps
      muscles, the mean peak torque deficit of the injured limb was 14 +/- 15% in the
      painless group and 15 +/- 15% in the pain group at speed of 60 degrees /s (P =
      0.71, [95% CI for the group difference = -11% to 10%]). At a speed of 180 degrees
      /s, the corresponding deficits were 9 +/- 11% and 14 +/- 17% (P = 0.46, [95% CI
      for the group difference = -14% to 5%]). CONCLUSION: Based on this prospective
      study, we conclude that anterior knee pain after intramedullary nailing of a
      tibial shaft fracture, although of multifactorial origin, may be related to
      deficiency in the flexion strength of the thigh muscles.

PMID- 14676553
TI  - The magnetic attraction of lower extremity external fixators in an MRI suite.
AB  - OBJECTIVES: To determine the magnetic attraction of 10 currently available lower
      extremity external fixators in the MRI suite and to test fixators with minimal or
      no magnetic attraction for the presence of temperature elevation during a 30
      minute MRI scan. DESIGN: Consecutive testing of selected tibial external fixation
      models in an identical manner. SETTING: Level 1 trauma center. CONSTRUCTS: Ten
      commercially available external fixators used for lower extremity injuries
      applied to saw bone tibia. INTERVENTION: External fixators suspended in testing
      apparatus were placed at three locations in the MRI suite for magnetic testing.
      Fixators with minimal attraction were scanned for 30 minutes. MAIN OUTCOME
      MEASUREMENTS: Magnetic attraction was measured with a digital scale, and
      temperature measurements were obtained with a digital thermometer and
      thermocouple. RESULTS: The Ilizarov with carbon fiber rings, Richards Hex-Fix,
      and Large Synthes External Fixator had <1 kg of magnetic attraction at all three
      locations. No component of these fixators experienced >2 degrees of temperature
      elevation after a 30-minute MRI scan. The EBI Dynafix with Ankle Clamp, EBI
      Dynafix, and EBI Dynafix Hybrid along with the Hoffman II, Hoffman II Hybrid,
      Ilizarov with stainless steel rings, and Synthes Hybrid had >1 kg of magnetic
      attraction at all three locations. CONCLUSIONS: Many commercially available
      external fixators have components and spring clamps that have significant
      magnetic attraction to the MRI scanner. Fixators that have <1 kg of attraction do
      not experience significant heating during MRI.

PMID- 14676554
TI  - Results of palmar plating of the lunate facet combined with external fixation for
      the treatment of high-energy compression fractures of the distal radius.
AB  - OBJECTIVES: The study evaluated the outcome of the treatment of patients who
      sustained high-energy, compression-type injuries of the distal radius. DESIGN:
      The retrospective study evaluated the outcome of reduction and plating of the
      lunate facet in conjunction with standard external fixation. SETTING: A Level I
      trauma center. PATIENTS: Inclusion criteria for study participation included: 1)
      age between 18 and 65 years of age with no evidence of concomitant metabolic bone
      disease; and 2) a 3- or 4-part compression type fracture of the distal radius
      with residual displacement of the palmar lunate facet despite reduction of the
      dorsal cortex by the application of an external fixator. INTERVENTION: Fractures
      were treated with palmar plating of the depressed lunate facet combined with
      dorsal external fixation. MAIN OUTCOME MEASUREMENTS: Posttreatment evaluations
      consisted of measurements of range of motion, grip strength, radiographic
      evaluations, and completion of Disability of Arm, Shoulder, and Hand
      questionnaires. RESULTS: Three months after surgery, 20 of 21 patients exhibited
      full range of motion at the MCP/PIP joints. At the 2-year follow-up, an average
      palmar tilt of +1.0 degrees, radial inclination of 24 degrees, radial length of
      12 mm, ulnar variance of 0.5 mm, intra-articular gap of 0.1 mm, and intra
      articular step-off of 0.3 mm was documented. Using the Garland and Werley rating
      system, results were rated as excellent or good for 18 wrists, fair for 2 wrists,
      and poor for 1 wrist. Mean Disability of Arm, Shoulder, and Hand functional
      scores and athletic scores improved at 6 months. CONCLUSIONS: Reduction and
      plating of the lunate facet in conjunction with standard external fixation
      permits: 1) visualization and reduction of the palmar lunate facet; and 2)
      reduction of palmar tilt to neutral tilt without significant radial shortening.
      This technique should be considered as an acceptable option in the treatment of
      high-energy fractures of the distal radius.

PMID- 14676555
TI  - Prevention of hip lag screw cut-out by cement augmentation: description of a new
      technique and preliminary clinical results.
AB  - Cement augmentation of hip lag screws to avoid cut-out displacement is
      classically described, along with a number of technical drawbacks. In a series of
      six elderly patients with hip fractures in osteoporotic bone, we illustrate
      catheter-assisted delivery of limited amounts of a new bisphenol-a-glycidyl
      dimethacrylate (bis-GMA)-based composite into hip compression screw threads,
      enabling significant increase in insertional torque compared with unaugmented
      screws. In two patients, unaugmented screws that did not initially purchase were
      tightened with a minimum torque of 1 N-m after augmenting with bis-GMA-based
      composite. No screw or femoral head displacement relative to baseline (2 days
      postoperative) was seen in any patient on serial x-rays taken up to 6 months
      after surgery. This technique adds approximately 10 minutes to surgery time.
      Advantages of bis-GMA-based composite over traditional PMMA augmentation include
      mixing on-demand, the ability to make repeated injections over extended periods
      in the event of femoral head perforations (in one patient in this series),
      precise placement of adequately small volumes of material, and a lower exotherm.
      Potentially, this bis-GMA-based composite may reduce the frequency of cut-out
      complications by enhancing bone-implant interface.

PMID- 14676556
TI  - A technique for reducing splash exposure during pulsatile lavage.
AB  - Pulsatile lavage is a frequently used method among orthopaedic traumatologists at
      our institution in the management of open fractures and contaminated wounds. Due
      to the pressure generated by the pulsatile lavage systems, splash exposure in the
      operating room environment becomes an unavoidable occurrence. The potential
      exists for a mucocutaneous exposure for either the surgeon or the operating room
      personnel. We have devised a method of decreasing the exposure risk to surgeons
      and operating room personnel during the pulsatile lavage irrigation portion of
      the procedure. An x-ray cassette drape is placed over the affected limb with
      enough clamps to create a closed system. Then small holes are created for the
      pulsatile lavage and the suction tubing, and the irrigation procedure is begun.
      This inexpensive cassette cover has proved to be a substantial advantage in our
      institution for decreasing mucocutaneous exposure.

PMID- 14676557
TI  - Unusual osteonecrosis of the femoral head misdiagnosed as a stress fracture.
AB  - We report a case of femoral head osteonecrosis that originally was misdiagnosed
      as a femoral neck stress fracture by plain radiography and magnetic resonance
      imaging. The correct diagnosis was made using pinhole bone scintigraphy, which
      revealed a completely cold lesion of the entire femoral head, confirmed by
      histologic examination. The patient was treated with muscle pedicle bone
      grafting, and 3 months postoperatively, pinhole bone scintigraphy showed improved
      vascularity of the femoral head.

PMID- 14676558
TI  - Posttraumatic radioulnar synostosis treated with a free vascularized fat
      transplant and dynamic splint: a report of two cases.
AB  - Two cases of posttraumatic radioulnar synostosis are presented. The patients were
      treated with excision of the cross-union and interposition of a free vascularized
      fat transplant. A newly devised pronation-supination dynamic splint was employed
      for 3 months postoperatively in both patients. After a 1-year postoperative
      follow-up, an increased range of motion was restored in both cases, and there was
      no evidence of recurrent synostosis formation in subsequent radiographs. We
      suggest that an interposed vascularized fat graft may be an ideal biologic
      barrier to fill the space created by cross-union excision.

PMID- 14676559
TI  - Late extensor pollicis longus rupture following displaced distal radius and ulna
      fractures in a child.
AB  - A 12-year-old boy experienced rupture of the extensor pollicis longus 1 month
      after closed reduction and percutaneous pinning of a markedly volarly displaced
      fracture of the distal radius and ulna. Late extensor pollicis longus rupture is
      a rare complication in children, especially following a markedly displaced
      fracture.

PMID- 14676560
TI  - Hybrid external fixation of the proximal tibia: strategies to improve frame
      stability.

PMID- 14676561
TI  - Effect of propofol and clonidine on cerebral blood flow velocity and carbon
      dioxide reactivity in the middle cerebral artery.
AB  - This study was designed to evaluate the effects of propofol alone and propofol
      clonidine combination on human middle cerebral artery blood flow velocity (Vmca)
      and cerebrovascular carbon dioxide (CO2) response by using transcranial Doppler
      ultrasonography. Mean Vmca in response to changes in arterial partial pressure of
      CO2 (Paco2) was determined under the following conditions: awake (group 1),
      propofol anesthesia (group 2), and combined propofol-clonidine anesthesia (group
      3). Normocapnic, hypercapnic, and hypocapnic values of heart rate, mean arterial
      pressure, partial end-tidal CO2 pressure, Paco2, and Vmca were obtained. The mean
      Vmca in groups 2 and 3 was significantly lower than that in group 1 at each level
      of Paco2. The calculated Vmca at each level of Paco2 was not different between
      groups 2 and 3. There was a correlation between Paco2 and Vmca in all groups, but
      in the anesthetized groups the effect of Paco2 on Vmca was attenuated. The
      present data demonstrated that clonidine-propofol does not change CO2 reactivity
      compared with propofol alone, but both anesthetics attenuate cerebral blood flow
      compared with awake controls.

PMID- 14676562
TI  - Jugular bulb oxygen saturation under propofol or sevoflurane/nitrous oxide
      anesthesia during deliberate mild hypothermia in neurosurgical patients.
AB  - Sevoflurane and propofol have been widely used as anesthetic agents for
      neurosurgery. Recent evidence has suggested that the influence of these
      anesthetics on cerebral oxygenation may differ. In the present study, the authors
      investigated jugular bulb oxygen saturation (SjO2) during propofol and
      sevoflurane/nitrous oxide anesthesia under mildly hypothermic conditions. After
      institutional approval and informed consent, 20 patients undergoing elective
      craniotomy were studied. Patients were randomly divided to the group S/N2O
      (sevoflurane/nitrous oxide/fentanyl anesthesia) or the group P (propofol/fentanyl
      anesthesia). After induction of anesthesia, the catheter was inserted retrograde
      into the jugular bulb and SjO2 was analyzed. During the operation, patients were
      cooled and tympanic membrane temperature was maintained at 34.5 degrees C. SjO2
      was measured at normocapnia during mild hypothermia and at hypocapnia during mild
      hypothermia. There were no statistically significant differences in demographic
      variables between the groups. During mild hypothermia, SjO2 values were
      significantly lower in group P than in group S/N2O. The incidence of SjO2 less
      than 50% under mild hypothermic-hypocapnic conditions was significantly higher in
      group P than in group S/N2O. These results suggest that hyperventilation should
      be more cautiously applied during mild hypothermia in patients anesthetized with
      propofol and fentanyl versus sevoflurane/nitrous oxide/fentanyl.

PMID- 14676563
TI  - Using the intubating laryngeal mask airway for ventilation and endotracheal
      intubation in anesthetized and unparalyzed acromegalic patients.
AB  - Airway management may be difficult in acromegalic patients. The purpose of the
      study was to evaluate the intubating laryngeal mask airway (ILMA) as a primary
      tool for ventilation and intubation in acromegalic patients. Twenty-three
      consenting consecutive adult acromegalic patients presenting for transsphenoidal
      resection of pituitary adenoma were enrolled in the study. Anesthesia was induced
      using propofol (1.5 mg/kg followed by 0.5-mg/kg increments); the ILMA was
      inserted when the bispectral index fell below 50. The ILMA was successful as a
      primary airway for oxygenation and ventilation at the first attempt for 21 (91%)
      patients, while 2 (9%) patients required a second attempt. Patient movement was
      noticed in five (21.7%) of the patients during ILMA insertion. An attempt at
      tracheal intubation through the ILMA was performed following administration of a
      mean 395 +/- 168-mg dose of propofol. Overall success rates for tracheal
      intubation were 82% (19 patients). The first-attempt success rate for tracheal
      intubation was 52.6% (10 patients), second- and third-attempt success rates were
      42.1% (8 patients) and 5.3% (1 patient), respectively. Coughing or movement
      during intubation was observed in 12 (63.2%) of the patients. Direct laryngoscopy
      permitted intubation in three cases and blind intubation using a bougie in the
      fourth case. ILMA can be used as a primary airway for oxygenation in acromegalic
      patients (manual bag ventilation), but the rate of failed blind intubation
      through the ILMA precludes its use as a first choice for elective airway
      management.

PMID- 14676564
TI  - Perioperative management of diabetes insipidus in children [corrected].
AB  - Managing children with diabetes insipidus (DI) in the perioperative period is
      complicated and frequently associated with electrolyte imbalance compounded by
      over- or underhydration. In this study the authors developed and prospectively
      evaluated a multidisciplinary approach to the perioperative management of DI with
      a comparison to 19 historical control children. Eighteen children either with
      preoperative DI or undergoing neurosurgical operations associated with a high
      risk for developing postoperative DI were identified and managed using a
      standardized protocol. In all patients in whom DI occurred during or after
      surgery, a continuous intravenous infusion of aqueous vasopressin was initiated
      and titrated until antidiuresis was established. Intravenous fluids were given as
      normal saline and restricted to two thirds of the estimated maintenance rate plus
      amounts necessary to replace blood losses and maintain hemodynamic stability. In
      all children managed in this fashion, perioperative serum sodium concentrations
      were generally maintained between 130 and 150 mEq/L, and no adverse consequences
      of this therapy developed. In the 24-hour period evaluated, the mean change in
      serum sodium concentrations between the historical controls was 17.6 +/- 9.2
      mEq/L versus 8.36 +/- 6.43 mEq/L in those children managed by the protocol.
      Hyponatremia occurred less frequently in the children managed with this protocol
      compared with historical controls.

PMID- 14676565
TI  - Dexmedetomidine and neurocognitive testing in awake craniotomy.
AB  - Patients are selected for awake craniotomy when the planned procedure involves
      eloquent areas of the brain, necessitating an awake, cooperative patient capable
      of undergoing neurocognitive testing. Different anesthetic combinations,
      including neurolept, propofol with or without opioid infusions, and asleep-awake
      asleep techniques, have been reported for awake craniotomy. In all these
      techniques, respiratory depression has been reported as a complication. In this
      case series dexmedetomidine, the highly selective alpha-2 adrenoreceptor agonist,
      was selected for its lack of respiratory depression as well as its sedative and
      analgesic properties. The charts of 10 consecutive patients who underwent awake
      craniotomy with dexmedetomidine infusion were reviewed. Five of the patients
      underwent "asleep-awake" technique with a laryngeal mask airway and volatile
      agent. Five patients received moderate to conscious sedation. All patients
      received a dexmedetomidine load of 0.5 to 1.0 microg/kg over 20 minutes followed
      by an infusion at rates of 0.01 to 1.0 microg/kg per hour. Four patients had
      extensive sensory and motor testing, and six underwent neurocognitive testing,
      including naming, reading, counting, and verbal fluency. There were no permanent
      neurologic deficits, except one patient who had an exacerbation of preoperative
      language difficulties. Dexmedetomidine appears to be a useful sedative for awake
      craniotomy when sophisticated neurologic testing is required.

PMID- 14676566
TI  - Unsuspected pheochromocytoma: von Hippel-Lindau disease.
AB  - The authors report a case of cerebellar hemangioma excision in a 13-year-old girl
      with unsuspected pheochromocytoma. This patient had an uneventful attempt at
      embolization of her tumor under general anesthesia but manifested hypertensive
      crisis during the intracranial surgery. The intra- and postoperative course of
      events and management are described. The possible causes leading to hypertension
      in an unsuspected pheochromocytoma are discussed. The anesthetic management of
      this patient for excision of pheochromocytoma is also presented.

PMID- 14676567
TI  - Acute parotitis following sitting position neurosurgical procedures: review of
      five cases.
AB  - Acute bacterial parotitis subsequent to major abdominal surgery is well
      documented, reportedly occurring in as many as 0.1% of patients. Postoperative
      parotitis has been reported between 1 to 15 weeks after surgery, commonly
      appearing within 2 weeks of the procedure. However, postoperative parotitis has
      not been reported previously after neurosurgical procedures. The authors report
      five cases of postoperative parotitis after neurosurgical operations in the
      sitting position with mild flexion and rotation of the head. This group of
      patients accounted for 0.16% of all craniotomy and 1.9% of all sitting position
      neurosurgical procedures performed in the authors' institution from 1996 through
      2001. Neck flexion and head tilt in the sitting position might have an influence
      on acute parotitis. The authors found that the side of the parotitis was on the
      opposite side of the head rotation. Dehydration therapy may also be a
      contributing factor. The objective of this paper is to state that parotitis is a
      possible complication in neurosurgical patients operated on in sitting position
      and to discuss its pathophysiology and treatment options.

PMID- 14676568
TI  - Effects of anesthetic agents and physiologic changes on intraoperative motor
      evoked potentials.
AB  - Motor evoked potentials (MEPs) have shown promise as a valuable tool for
      monitoring intraoperative motor tract function and reducing postoperative plegia.
      MEP monitoring has been reported to contribute to deficit prevention during
      resection of tumors adjacent to motor structures in the cerebral cortex and
      spine, and in detecting spinal ischemia during thoracic aortic reconstruction.
      Many commonly used anesthetic agents have long been known to depress MEP
      responses and reduce MEP specificity for motor injury detection. Although new
      stimulation techniques have broadened the spectrum of anesthetics that can be
      used during MEP monitoring, certain agents continue to have dose-dependent
      effects on MEP reliability. Understanding the effects of anesthetic agents and
      physiologic alterations on MEPs is imperative to increasing the acceptance and
      application of this technique in the prevention of intraoperative motor tract
      injury. This review is intended as an overview of the effects of anesthetics and
      physiology on the reproducibility of intraoperative myogenic MEP responses,
      rather than an analysis of the sensitivity and specificity of this monitoring
      method in the prevention of motor injury.

PMID- 14676569
TI  - Secondary injuries in brain trauma: effects of hypothermia.
AB  - Hypothermia has been shown to be cerebroprotective in traumatized brains.
      Although a large number of traumatic brain injury (TBI) studies in animals have
      shown that hypothermia is effective in suppressing a variety of damaging
      mechanisms, clinical investigations have shown less consistent results. The
      complexity of damaging mechanisms in human TBI may contribute to these
      discrepancies. In particular, secondary injuries such as hypotension and
      hypoxemia may promote poor outcome. However, few experimental TBI studies have
      employed complex models that included such secondary injuries to clarify the
      efficacy of hypothermia. This review discusses the effects of hypothermia in
      various TBI models addressing primary and acute secondary injuries. Included are
      recently published clinical data using hypothermia as a therapeutic tool for
      preventing or reducing the detrimental posttraumatic secondary injuries and
      neurobehavioral deficits. Also discussed are recent successful applications of
      hypothermia from outside the TBI realm. Based on all available data, some general
      considerations for the application of hypothermia in TBI patients are given.

PMID- 14676570
TI  - Many mechanisms for hsp70 protection from cerebral ischemia.
AB  - Overexpression of inducible Hsp70 has been shown to provide protection from
      cerebral ischemia both in animal models of stroke and in cell culture models. New
      work suggests that there are multiple routes of cell death, including apoptotic
      and necrotic cell death. Hsp70 is known to protect from both necrotic and
      apoptotic cell death. In addition to the well-studied role of Hsp70 as a
      molecular chaperone assisting in correct protein folding, several new mechanisms
      by which Hsp70 can prevent cell death have been described. Hsp70 is now known to
      regulate apoptotic cell death both directly by interfering with the function of
      several proteins that induce apoptotic cell death as well as indirectly by
      increasing levels of the anti-death protein bcl-2. Despite these new insights
      into the ways in which Hsp70 functions as an anti-death protein, further
      surprises are likely as we continue to gain insight into the functioning of this
      multifaceted protein.

PMID- 14676571
TI  - Heart rate variability and brain death.

PMID- 14676572
TI  - Threats and opportunities in pre-hospital management of traumatic brain injury.

PMID- 14676573
TI  - Acute visual loss following cardiopulmonary bypass: model case presentation and
      discussion.

PMID- 14676574
TI  - Visual loss after spine surgery.

PMID- 14676575
TI  - Neurotoxicity of lidocaine: implications for spinal anesthesia and
      neuroprotection.

PMID- 14676576
TI  - Complications of regional anesthesia: nerve injury and peripheral neural
      blockade.

PMID- 14676577
TI  - Clinical trials in traumatic brain injury: lessons for the future.
AB  - Thus far, none of the neuroprotective drugs that have been tested to reduce or
      prevent secondary ischemic brain damage have been shown clear benefit. We will
      attempt to identify factors that may be responsible for some of these failures.
      We also will give our thoughts on how to prevent these pitfalls in the usefulness
      and criteria for use of animal models for traumatic brain injury to depict human
      head injury are discussed. Clearly, mechanism-driven trials, in which individual
      pathophysiological mechanisms are targeted, are more likely to show benefit in
      this heterogeneous patient population. Other factors, such as the effect of brain
      penetration, safety and tolerability of the compound, and the interface between
      the pharmaceutical industry and academics are a major influence in the success of
      these trials. Furthermore, the way trials have been analyzes in the past may not
      always have been be the most appropriate to show benefits. It is clear that a
      multi-targeted approach is necessary to address the complicated and closely
      related mechanisms seen after traumatic and or ischemic brain damage.

PMID- 14676578
TI  - Pharmacologic protection from ischemic neuronal injury.

PMID- 14676579
TI  - Regulation by sulfanylurea receptor type 1 of a non-selective cation channel
      involved in cytotoxic edema of reactive astrocytes.
AB  - Hypoxia-ischemia and ATP depletion are associated with cytotoxic edema of glial
      cells, but mechanisms involved remain incompletely characterized. We examined
      morphologic and electrophysiological responses of freshly isolated native
      reactive astrocytes (NRAs) following exposure to NaN3, which depletes cellular
      ATP. NaN3 caused profound and sustained depolarization due to activation of a
      novel 35 pS Ca2+-activated, [ATP]i-sensitive non-selective cation (NCCa-ATP)
      channel found in >90% of excised membrane patches. This channel exhibited
      significantly different properties compared with previously reported NCCa-ATP
      channels, including different sensitivity to block by various adenine nucleotides
      (EC50=0.79 microM for [ATP]i, with no block by AMP or ADP), and activation by
      submicromolar [Ca]i. In addition, the channel was found to be regulated in a
      manner identical to that of SUR1-regulated KATP channels, including high affinity
      block by glybenclamide and tolbutamide, and opening by diazoxide. mRNA
      transcription and protein expression of SUR1 but not SUR2 were confirmed in
      reactive astrocytes both in situ and after isolation, whereas Kir6.x, which forms
      the pore-forming subunit of the KATP channel, was not expressed. Channel opening
      by [ATP]i depletion or exposure to diazoxide caused blebbing of the cell
      membrane, whereas [ATP]i depletion in the presence of glybenclamide did not.
      These findings are consistent with participation of this channel in cation flux
      involved in cell swelling. This novel channel may play an important role in the
      pathogenesis of brain swelling.

PMID- 14676580
TI  - Neuroprotection by Na+ channel blockade.

PMID- 14676581
TI  - Neurologic injury after cardiopulmonary bypass surgery.

PMID- 14676582
TI  - G-protein activation decreases the isoflurane inhibition of N-type Ca2+ currents.
      An increase in the isoflurane blocking potency of N-type Ca2+ currents may
      contribute to the known neuroprotection action of isoflurane during ischemia.

PMID- 14676583
TI  - Mechanisms of neuronal death and neuroprotection.

PMID- 14676584
TI  - The Second World Congress of Pediatric Gastroenterology, Hepatology and
      Nutrition: Paris, 3-7 July 2004.

PMID- 14676585
TI  - Long chain polyunsaturated fatty acids in chronic childhood disorders: panacea,
      promising, or placebo.

PMID- 14676586
TI  - Diabetes and gastrointestinal tract: the intrigue continues.

PMID- 14676587
TI  - Rectal sparing despairing.

PMID- 14676588
TI  - Severe functional constipation in child: what is the solution?

PMID- 14676589
TI  - Helicobacter pylori and gastroesophageal reflux disease: a complex organism in a
      complex host.

PMID- 14676590
TI  - Neonatal enteropathies: defining the causes of protracted diarrhea of infancy.
AB  - The underlying causes of chronic diarrhea beginning early in life are
      increasingly well defined. Infectious and post-infectious enteropathies and food
      sensitive/allergic enteropathy account for the majority of cases. Recent
      attention has focused on characterizing defined entities, which cause protracted
      diarrhea in infants and young children. Disorders of intestinal ion transport
      usually present at birth following a pregnancy complicated by polyhydramnios.
      Intestinal mucosal biopsies show normal architect with intact villus-crypt axis.
      Neonatal enteropathies, by contrast, are characterized by blunting of the villi.
      These include microvillus inclusion disease, tufting enteropathy, autoimmune
      enteropathy and IPEX syndrome - and it is these conditions that are the subject
      of the current review.

PMID- 14676591
TI  - Water and electrolyte salvage in an animal model of dehydration and malnutrition.
AB  - BACKGROUND AND AIM: Recently, a new oral rehydration solution (ORS) called
      Resomal has been designed specifically for children with severe malnutrition. The
      aim of this study was to assess the effect of malnutrition on renal and
      intestinal responses to dehydration, and to compare intestinal water and
      electrolyte absorption from Resomal and from the standard World Health
      Organization-Oral Rehydration Solution (WHO-ORS). METHOD: Malnutrition was
      achieved in a rabbit model by feeding the animals daily for 30 days with half the
      amount of food that a well-nourished group of control animals had consumed on the
      previous day. Dehydration was achieved by water deprivation for 46 hours in both
      control and malnourished rabbits. At 46 hours, dehydration was assessed by
      changes in body weight, urinary volume and osmolarity, and blood urea nitrogen
      concentration. At that time active colonic and jejunal mucosal electrolyte
      transport in Ussing chambers was also measured. Small intestinal absorption of
      water, sodium, and potassium was measured in vivo during intestinal perfusion of
      the two ORSs and in vitro by measurement of mucosal electrogenic glucose
      stimulated sodium absorption across intestinal patches. RESULTS: Compared to
      controls (C), well-nourished but dehydrated (C+D) animals lost 12% of their body
      weight, with an 87% reduction in urine volume, a 110% increase in urine
      osmolality, and a 94% increase in blood urea nitrogen. In the colon of C+D
      animals, short-circuit current (Isc) and net sodium transepithelial flux (JNa+
      net) were increased. Almost identical results were obtained in malnourished and
      dehydrated (M+D) animals. In the jejunum, net in vivo absorption of water
      (JWater), sodium (JNa+), and potassium (JK+) were increased during standard ORS
      infusion in both dehydrated groups. During Resomal infusion, water absorption was
      the same as seen with WHO-ORS, but sodium absorption was reduced, and potassium
      absorption was increased in both well-nourished and malnourished dehydrated
      animals. In vitro, compared to controls, the glucose-stimulated short-circuit
      current (DeltaIsc), JNa+ net and G were increased in both dehydrated groups.
      CONCLUSION: During experimental dehydration, the kidney and large intestine
      salvage water and electrolytes, thus reducing the consequences of dehydration.
      These findings indicate that jejunal water absorption from Resomal and WHO-ORS is
      increased during dehydration, but Resomal allows for less sodium and more
      potassium to be absorbed, both in well-nourished and malnourished dehydrated
      rabbits.

PMID- 14676592
TI  - Zinc with oral rehydration therapy reduces stool output and duration of diarrhea
      in hospitalized children: a randomized controlled trial.
AB  - OBJECTIVES: The authors evaluated the effect of zinc treatment as an adjunct to
      oral rehydration therapy on stool output and diarrheal duration in children with
      acute noncholera diarrhea with dehydration. METHODS: This double-blind,
      randomized, controlled trial was conducted at two urban hospitals in New Delhi. A
      total of 287 dehydrated male patients, ages 3 to 36 months, with diarrhea for
      <or= 72 hours were enrolled. They were assigned to zinc or placebo by a
      randomization scheme stratified by age (<or= or >12 months) and weight for height
      (65%-80% or >80% National Centre for Health Statistics median). Participants in
      the zinc group received 15 mg (<or=12 months) or 30 mg (>12 months) elemental
      zinc daily in three divided doses for 14 days. The main outcome measures were
      stool output and diarrheal duration. RESULTS: Zinc treatment reduced total stool
      output (ratio of geometric means, 0.69; 95% confidence interval [CI]: 0.48, 0.99)
      and stool output per day of diarrhea (ratio of geometric means, 0.76; 95% CI:
      0.59, 0.98). The risk of continued diarrhea was lower (relative hazards, 0.76;
      95% CI: 0.59, 0.97) and the proportion of diarrheal episodes lasting >or= 5 days
      (odds ratio, 0.49; 95% CI: 0.25, 0.97) or >or= 7 days was less (odds ratio, 0.09;
      95% CI: 0.01, 0.73) in the zinc group. CONCLUSIONS: This study demonstrates a
      beneficial effect of zinc administered during acute diarrhea on stool output,
      diarrheal duration, and proportion of episodes lasting more than 7 days. The
      effects are large enough to merit routine use of zinc during acute diarrhea in
      developing countries.

PMID- 14676593
TI  - Octreotide therapy for control of acute gastrointestinal bleeding in children.
AB  - OBJECTIVES: To evaluate the outcomes of octreotide use in children with
      gastrointestinal bleeding with or without portal hypertension. METHODS: The
      medical charts of children who received continuous octreotide infusion for the
      indication of gastrointestinal bleeding from January 1995 to December 2000 were
      retrospectively reviewed. RESULTS: Twenty-one children with portal hypertension
      received octreotide infusions (1-2 microg/kg/h) during 35 gastrointestinal
      bleeding episodes. The duration of infusion ranged from 19 hours to 7 days.
      Bleeding ceased in 71% of children. Post-treatment rebleeding occurred in 52%,
      and the mortality was 19%. Response to octreotide, rebleeding, and mortality did
      not differ significantly between patients with or without intrinsic liver
      disease. Twelve children with gastrointestinal bleeding unrelated to portal
      hypertension received octreotide during 14 episodes. The duration of octreotide
      ranged from 3 hours to 36 days. Fifty percent of children had resolution of
      bleeding during the infusion. Post-treatment rebleeding occurred in 29%, and the
      mortality was 50%. No major adverse events were observed in either group.
      CONCLUSIONS: A high rate of bleeding control was achieved with octreotide during
      acute gastrointestinal bleeding in children with portal hypertension. However,
      controlled studies are needed for more definitive description of its clinical
      effects. The role of octreotide is less clear in gastrointestinal bleeding
      unrelated to portal hypertension.

PMID- 14676594
TI  - Vitamin E treatment in pediatric obesity-related liver disease: a randomized
      study.
AB  - OBJECTIVE: A beneficial role of antioxidants in hepatopathic obese individuals
      has hitherto been inferred only from uncontrolled pilot studies. The authors
      compared the effect of vitamin E and weight loss on transaminase values and on
      ultrasonographic bright liver in a controlled group of children with obesity
      related liver dysfunction. METHODS: Twenty-eight children with obesity-related
      hypertransaminasemia and bright liver were randomly allocated to two single-blind
      groups: group 1 (n = 14) treated with a low-calorie diet associated with oral
      placebo for 5 months, and group 2 (n = 14) treated with a low-calorie diet
      associated with oral vitamin E (400 mg/d x 2 months, 100 mg/d x 3 months).
      Transaminase values and ultrasonographic liver brightness along with weight loss
      and vitamin E levels were monitored. RESULTS: Variations in transaminase levels
      and percentage of patients with normalized transaminase values were comparable in
      the two groups. The disappearance of bright liver was observed only in patients
      who lost weight and was twice as common in patients from group 1. Two subgroups
      of patients with complete normalization of transaminase values emerged as a
      consequence of controlled adherence to diet alone (n = 6; significant decrease of
      percent overweight: P = 0.0019 ) and to vitamin E alone (n = 7; unmodified
      percent overweight and significant increase of vitamin E/cholesterol ratio: P <
      0.0001). Changes in treatment-induced alanine aminotransferase levels in these
      two subgroups were comparable at month 2, whereas values at month 5 were
      significantly lower in the subgroup adherent to diet alone (P = 0.04). In the
      subgroup adherent to vitamin E alone, after 2 months washout, transaminase
      remained stable in 5 patients and increased in 2; bright liver persisted in all.
      CONCLUSIONS: Oral vitamin E warrants consideration in obesity-related liver
      dysfunction for children unable to adhere to low-calorie diets.

PMID- 14676595
TI  - Serum lipids in preterm infants fed a formula supplemented with nucleotides.
AB  - BACKGROUND: The effect of dietary nucleotides on lipid metabolism has been the
      subject of clinical studies with conflicting results. We measured serum
      triglycerides, total cholesterol (total-C), and lipoprotein cholesterol levels
      (HDL-C, LDL-C, and VLDL-C) in preterm neonates fed formula with and without
      nucleotide supplements. METHODS: This prospective, randomized, controlled study
      included 150 healthy preterm neonates (gestational age, 33.0 +/- 1.9 weeks)
      matched for gestational age, birth weight, and gender. Subjects were assigned at
      birth to receive either a standard milk formula supplemented with nucleotides
      (group F-NT) or the same formula without nucleotides (group F). Serum was
      obtained before discharge (29.1 +/- 10.0 days of life) and triglycerides, total
      C, and HDL-C were determined enzymatically. LDL-C and VLDL-C were estimated by
      the Friedewald formula. For statistical analysis t test, Mann Whitney-U test, two
      way ANOVA, and chi2 test were used, as appropriate. The influence of several
      factors on serum lipid levels was evaluated by linear regression analysis.
      RESULTS: Serum triglycerides, total-C, and VLDL-C levels did not differ between
      groups. HDL-C levels (median; 25th-75th percentiles) were significantly higher (P
      < 0.001) in group F-NT (48.0 mg/dL; 40.5-57.0 mg/dL) than in group F (34.5 mg/dL;
      27.2-44.0 mg/dL). On the contrary, LDL-C levels (median; 25th-75th percentiles)
      were significantly lower (P < 0.001) in group F-NT (39.0 mg/dL; 26.0-54.0 mg/dL)
      than in group F (65.0 mg/dL; 41.0-73.0 mg/dL). In the multiple regression
      analysis, nucleotide supplementation was identified as one of the controlled
      independent factors influencing serum HDL-C and LDL-C levels. CONCLUSIONS:
      Preterm neonates fed from birth with formula supplemented with nucleotides have
      significantly higher HDL-C and lower LDL-C serum levels than do neonates fed
      unsupplemented formula. The clinical relevance of these results remains to be
      elucidated.

PMID- 14676596
TI  - Autonomic neuropathy and gastrointestinal motility disorders in children and
      adolescents with type 1 diabetes mellitus.
AB  - INTRODUCTION: There is little information on the gastrointestinal motility
      abnormalities and autonomic neuropathy of children with gastrointestinal symptoms
      and type 1 diabetes mellitus (T1DM). METHODS: The authors studied 33 consecutive
      patients (mean age, 15.3 years; 13 males) with T1DM (median duration, 7.7 years)
      attending the outpatient clinic because of chronic dyspepsia (CD; n = 14), or
      chronic constipation (CC; n = 19), and 48 consecutive non-T1DM patients (mean
      age, 13.7 years; 18 males), who presented with similar symptoms (18 with CD; 30
      with CC). Fasting serum motilin concentrations and cardiovascular autonomic
      function tests (CAFT) were assessed and compared with those of age- and gender
      matched healthy control subjects. Gastric emptying half time (GE t1/2) of a solid
      meal and mouth-to-anus transit time (MATT) were measured in patients with CD and
      CC, respectively. RESULTS: CAFT was comparable between patients with T1DM and
      healthy control subjects. GE t1/2 and MATT were not different between T1DM
      patients and non-T1DM patients with CD and CC, respectively. However, a
      marginally significant positive correlation was found in the patients with T1DM
      between GE t1/2 and blood glucose concentrations (R = 0.54; P = 0.08). In
      addition, serum motilin concentrations were significantly lower in patients with
      T1DM compared with healthy control subjects (P < 0.0005), and in patients with
      T1DM and higher serum glucose concentrations compared with those with lower serum
      glucose concentrations (P = 0.03). CONCLUSION: Autonomic neuropathy is not an
      etiological factor of gastrointestinal symptoms in children and adolescents with
      diabetes. Mild or moderate hyperglycemia does not affect gastrointestinal
      motility.

PMID- 14676597
TI  - Endoscopic rectal sparing in children with untreated ulcerative colitis.
AB  - BACKGROUND: Ulcerative colitis (UC) typically is associated with a confluent
      proctitis, whereas rectal sparing may be seen in large bowel Crohn disease (CD).
      A few studies have reported rectal sparing in UC and suggested that this might
      indicate a more severe form of the disease. This study aimed to determine the
      prevalence and prognostic significance of rectal sparing in children with newly
      diagnosed, untreated UC. METHODS: The records of all children with untreated UC
      presenting to a regional pediatric gastroenterology service between January 1996
      and December 2001 were retrospectively reviewed. Patients were divided into two
      groups according to the endoscopic appearance of the rectum: Group 1 (proctitis)
      and Group 2 (rectal sparing). Clinical features, intractability index (duration
      of active disease as a proportion of length of follow-up), response to treatment,
      relapse index (number of recurrences per year), and the need for surgery were
      compared. RESULTS: Thirty children with untreated UC were identified. Seven (23%)
      had rectal sparing at initial endoscopy, but disease distribution was otherwise
      similar in both groups. Presenting symptoms were similar in those with and
      without rectal sparing. In Group 1, 20 (87%) children achieved remission with
      initial medical treatment, compared with 3 (43%) in Group 2 (P < 0.05). The
      intractability index was higher in children with rectal sparing, but the
      difference was not statistically significant (P = 0.22). During a median follow
      up period of 2 years, one (4%) child in Group 1 and two (29%) children in Group 2
      experienced primary sclerosing cholangitis, and two (29%) children with rectal
      sparing required colectomy, compared with none in Group 1. CONCLUSIONS:
      Endoscopic rectal sparing was seen in 23% of children with newly diagnosed,
      untreated UC, but this feature did not correlate with presenting symptoms.
      However, the presence of rectal sparing may indicate more aggressive disease that
      is less responsive to medical treatment.

PMID- 14676598
TI  - Gastroesophageal reflux disease and Helicobacter pylori infection in
      neurologically impaired children: inter-relations and therapeutic implications.
AB  - BACKGROUND: The aim of this retrospective study was to assess the relationship
      between Helicobacter pylori infection and gastroesophageal reflux disease in a
      high-risk population of children. METHODS: Forty-three neurologically impaired
      pediatric patients with H. pylori had upper gastrointestinal endoscopy between
      1990 and 2000. Infection was confirmed by positive H. pylori culture or by
      identification of organisms in gastric biopsy specimens (fundus, n = 2; antrum, n
      = 3). Reflux esophagitis was diagnosed by ulceration of the esophageal mucosa at
      endoscopy. Four to 6 weeks after the completion of antibiotic treatment of H.
      pylori, a second endoscopy was performed and the gross appearance of the
      esophagus was recorded. RESULTS: At the first endoscopy, esophagitis was noted in
      14 of 43 patients. After treatment, H. pylori infection was eradicated in all 14
      patients with esophagitis but in only 19 of 29 (66%) of those with normal
      esophagus (P = 0.01). Esophagitis was still present in 4 of 14 (29%) patients who
      had esophagitis at the first endoscopy. Persistent esophagitis was only related
      to the presence of esophagitis before treatment (P = 0.02). In 29 patients with a
      normal esophagus at the first endoscopy, only one case of esophagitis was
      observed after H. pylori eradication. CONCLUSION: The data suggest that treatment
      of H. pylori infection should be considered in children with concomitant GERD,
      and such treatment is unlikely to either induce or exacerbate peptic esophagitis.

PMID- 14676599
TI  - Colostomy for treatment of functional constipation in children: a preliminary
      report.
AB  - OBJECTIVES: Surgery is indicated in very few children with intractable functional
      constipation. A number of operations have been described with unpredictable
      outcome and significant morbidity. The authors present a series of 10 children
      who underwent a Hartmann procedure with end colostomy formation. METHOD:
      Preoperative management, in addition to maximum conservative measures, included
      psychologic referral, rectal biopsy, transit studies, and contrast enemas. A
      standard Hartmann procedure was performed with on-table rectal washout, formation
      of a proximal sigmoid colostomy, limited anterior resection of hypertrophic
      proximal rectosigmoid, and oversewing of the rectal stump. RESULTS: The series
      includes 10 pediatric patients (4 female, 6 male), in whom constipation was first
      reported at a median age of 3 years (range, 2 months-7 years) and surgical
      referral was made at 8 years (range, 1-14 years). Surgery was performed at a
      median age of 9.5 years (range, 2-15 years), and the median postoperative stay
      was 5 days (range, 4-9 days). Complications occurred in four patients (transient
      mild rectal discharge in 2, stomal prolapse in 1, and an unrelated small bowel
      obstruction in 1 patient with an additional Mitrofanoff stoma). Median
      postoperative follow-up was 31 months (range, 9-56 months), and the children and
      parents were all completely satisfied with the stoma. CONCLUSION: Colostomy
      formation is a potential surgical option for severe functional constipation with
      low associated morbidity and high patient satisfaction.

PMID- 14676600
TI  - Functional fecal retention with encopresis in childhood.
AB  - OBJECTIVES: The most common cause of encopresis in children is functional fecal
      retention (FFR). An international working team suggested that FFR be defined by
      the following criteria: a history of >12 weeks of passage of <2 large-diameter
      bowel movements (BMs) per week, retentive posturing, and accompanying symptoms,
      such as fecal soiling. These criteria are usually referred to as the ROME II
      criteria. The aims of this study were to evaluate how well the ROME II criteria
      identify children with encopresis; to compare these patients to those identified
      as having FFR by historical symptoms or physical examination; to determine
      whether 1-year treatment outcome varied depending on which definition for FFR was
      used; and to suggest improvements to the ROME II criteria, if necessary. METHODS:
      Data were reviewed from the history and physical examination of 213 children with
      encopresis. One-year outcomes identified were failure, successful treatment, or
      full recovery. RESULTS: Only 88 (41%) of the patients with encopresis fit the
      ROME II criteria for FFR, whereas 181 (85%) had symptoms of FFR by history or
      physical examination. Thirty-two (15%) patients did not fit criteria for FFR, but
      only 6 (3%) appeared to have nonretentive fecal soiling. Rates of successful
      treatment (50%) and recovery (39%) were not significantly different in the two
      groups. CONCLUSIONS: The ROME II criteria for FFR are too restrictive and do not
      identify many children with encopresis who have symptoms of FFR. The author
      suggests that the ROME II criteria for FFR could be improved by including the
      following additional items: a history of BMs that obstruct the toilet, a history
      of chronic abdominal pain relieved by enemas or laxatives, and the presence of an
      abdominal fecal mass or rectal fecal mass.

PMID- 14676601
TI  - Lewis antigen expression in gastric mucosa of children: relationship with
      Helicobacter pylori infection.
AB  - OBJECTIVE: Lewis epithelial antigen expression has a role in Helicobacter pylori
      adherence, presumably mainly in cagA-positive strains. The authors investigated
      whether Lewis antigen expression in children's gastric mucosa was associated with
      H. pylori infection, cagA status, patient age, or presence of duodenal ulcer
      (DU). METHODS: The expression of Lewis A (Le(a)), B (Le(b)), X (Le(x)), and Y
      (Le(y)) was detected by immunohistochemistry in the antral and oxyntic mucosae of
      70 children. Children were divided in four age groups (<4 years; 4-8 years; 9-12
      years; and 13-18 years). RESULTS: Forty-seven of the 70 children had H. pylori
      and 17 had DU. The cagA status was determined by polymerase chain reaction in 34
      patients. Le(a) and Le(b) were expressed in 64% and 44% of the patients,
      respectively; Le(x) and Le(y) were expressed in the glands in all of the patients
      and in the superficial epithelium. Le(b) expression was more common among
      patients without H. pylori (15/23, 65%) than in those with H. pylori (16/47, 34%)
      (P = 0.03). In noninfected patients, Le(b) and superficial Le(y) expression were
      associated with increased age. Le(b) expression was more common in patients with
      chronic gastritis than in those with DU. Le(x) superficial expression was
      significantly associated with DU in patients with H. pylori. CONCLUSION: In
      children, the expression of Le(b) and Le(y) in the superficial gastric epithelium
      depends on age. Other receptors, such as Le(x), may have a role in H. pylori
      colonization, especially in patients with DU. Studies assessing the expression of
      Lewis antigens in children may contribute to an understanding of the mechanisms
      of acquisition of H. pylori infection.

PMID- 14676602
TI  - Weaning to hypoallergenic formula improves gut barrier function in breast-fed
      infants with atopic eczema.
AB  - OBJECTIVES: Infants may be sensitized to dietary antigens even during exclusive
      breast-feeding. Because food antigen traces in breast milk may have harmful
      effects on gut barrier function in infants with atopy, the authors sought to
      evaluate whether or not it is beneficial to shift such infants from breast milk
      to a hypoallergenic formula. METHODS: Fifty-six infants (mean age, 5.0 months)
      manifesting atopic eczema during exclusive breast-feeding were studied at weaning
      to a tolerated hypoallergenic formula. The urinary recovery ratios of orally
      administered lactulose and mannitol, fecal alpha-1 antitrypsin and urinary
      methylhistamine, and eosinophil protein X concentrations were assessed during
      breast-feeding and after weaning. RESULTS: The median (interquartile range, IQR)
      concentration of fecal alpha-1 antitrypsin was 2.3 mg/g (range, 1.2-3.3 mg/g)
      during breast-feeding and 0 (0.0-1.9 mg/g) after weaning to a tolerated
      hypoallergenic formula, z = -4.23, P < 0.0001. The urinary recovery ratio of
      lactulose and mannitol decreased from 0.029 (range, 0.021-0.042) to 0.023 (range,
      0.016-0.031), respectively, z = -3.45, P = 0.0006. Concomitantly, the atopic
      eczema improved, and the concentration of urinary eosinophil protein X decreased
      significantly. CONCLUSIONS: In breast-fed infants with atopy, gut barrier
      function is improved after cessation of breast-feeding and starting of
      hypoallergenic formula feeding.

PMID- 14676603
TI  - Granular cell tumor of the esophagus: report of a pediatric case and literature
      review.

PMID- 14676604
TI  - Pancreatic pseudocyst complicating hemolytic-uremic syndrome.

PMID- 14676605
TI  - Prenatal diagnosis of Alagille syndrome.

PMID- 14676606
TI  - Hydrolyzed versus nonhydrolyzed protein diet in short bowel syndrome in children.

PMID- 14676607
TI  - Fecal calprotectin in healthy term and preterm infants.

PMID- 14676608
TI  - Resolutions for the here and now.

PMID- 14676609
TI  - Gastroesophageal reflux disease: current treatment approaches.
AB  - Gastroesophageal reflux disease is a common, usually lifelong, disorder resulting
      from chronic abnormal exposure of the lower esophagus to gastric contents. Motor
      dysfunction of the lower esophageal sphincter is the primary cause of this
      disease. At this writing, no medical therapies can completely resolve abnormal
      lower esophageal sphincter function; therefore, the treatment of gastroesophageal
      reflux disease centers on suppression of intragastric acid secretion. Available
      acid-suppressant medications include proton pump inhibitors, H2-receptor
      antagonists, and antacids. Of these, the proton pump inhibitors are recognized
      generally as the mainstays of both short-term and long-term therapy for
      gastroesophageal reflux disease. All have a low incidence of side effects and are
      well tolerated by most patients. Five proton pump inhibitors are available
      currently for patients with gastroesophageal reflux disease. Of these,
      esomeprazole has shown greater efficacy in controlling intragastric acidity than
      the others. For patients with erosive esophagitis, esomeprazole has demonstrated
      higher healing rates and more rapid sustained resolution of heartburn than
      omeprazole or lansoprazole after up to 8 weeks of once-daily treatment. Because
      new therapies for gastroesophageal reflux disease are highly effective, patients
      can be reassured that their disease will be well controlled and their symptoms
      resolved with a safe and appropriate treatment.

PMID- 14676610
TI  - Inpatient bowel preparation order set: a means to enhance patient completion of
      bowel preparation medication.
AB  - Adequate bowel preparation is necessary for several diagnostic and surgical
      procedures. Inpatients appeared to be less adequately prepared than outpatients
      at the author's 100-bed hospital. A problem frequently encountered was incomplete
      administration of the ordered bowel preparation. Surgeons, gastroenterologists,
      and nurses from the endoscopy laboratory and medical-surgical floor were
      consulted for development of an order set to enhance completion of bowel
      preparation for inpatients.

PMID- 14676611
TI  - Cognitive dissonance theory and motivation for change: a case study.
AB  - Managers frequently seek ways to create effective and lasting change among
      employees. When attempting change, each manager must consider what will motivate
      a particular employee at a particular time. To create lasting change, it is
      believed that a change in attitudes, beliefs, or values may be necessary.
      Cognitive dissonance is purported to be a powerful motivator for change. People
      find consistency comfortable and prefer to be consistent in their thoughts,
      beliefs, emotions, values, attitudes, and actions. When inconsistency exists, an
      individual feels an imbalance or dissonance. To reduce this feeling of imbalance,
      individuals may change their attitude or behavior to regain the feeling of
      consistency. This article explores cognitive dissonance theory and discusses a
      situation in which it was used to produce effective and lasting change in a
      nursing work unit.

PMID- 14676612
TI  - Inflammatory bowel disease support groups: a primer for gastroenterology nurses.
AB  - This article discusses the importance of a support group for people living with
      inflammatory bowel disease. The support group provides these patients and their
      families with a social framework for promoting positive adjustment to the illness
      and seeks to improve the patients' quality of life. The use of a support group
      has been described in the literature as a method of helping patients and their
      families to face living with chronic illness, but relatively little has been
      written about support groups for people with inflammatory bowel disease and the
      role of the gastroenterology nurse. In this article, the benefit of support
      groups and the content of the intervention are discussed including health
      education, self-efficiency, coping skills, and ways to increase feelings of
      social acceptance.

PMID- 14676613
TI  - Biofeedback: its role in the treatment of chronic constipation.
AB  - Constipation accounts for more than 2.5 million physician visits a year.
      Treatment of constipation has been a long-standing and costly problem. Affecting
      approximately 4.5 million Americans, predominantly women and the elderly,
      constipation can be persistent and difficult to manage. With the great number of
      laxative products available, more than $350 to $400 million is spent on over-the
      counter laxatives each year. In addition to a complete history and physical
      examination, tests of anorectal function are useful in the assessment of
      defecation disorders. Approximately 50% of patients exhibit uncoordinated or
      dyssynergic defecation patterns. Biofeedback therapy may improve the symptoms of
      these patients. Biofeedback therapy is labor-intensive, expensive, and available
      only at a few centers. Although the concept of dyssynergic defecation has existed
      for only a few years, its therapy, based on neuromuscular conditioning, is
      gaining recognition. The biofeedback program from one Midwestern tertiary care
      center is described. Although much still needs to be learned regarding the
      etiology and pathophysiology of dyssynergic defecation, its management with
      biofeedback is shown to be efficacious and may prove to be the treatment of
      choice for patients with this dysfunction of the pelvic floor.

PMID- 14676614
TI  - SGNA Guideline: Performance of flexible sigmoidoscopy by registered nurses for
      the purpose of colorectal cancer screening.

PMID- 14676615
TI  - SGNA Position Statement: Performance of gastrointestinal manometry studies and
      provocative testing.

PMID- 14676616
TI  - East meets West: the use of traditional Chinese medicine for gastrointestinal
      disorders.

PMID- 14676617
TI  - Seeing the possibilities.

PMID- 14676618
TI  - The research committee.

PMID- 14676620
TI  - Bacterial responses to neutrophil phagocytosis.
AB  - PURPOSE OF REVIEW: This review focuses on adaptive bacterial interactions with
      neutrophils, emphasizing information communicated within the past year about
      bacterial factors that respond to contact with or phagocytosis by PMN. RECENT
      FINDINGS: Since the discovery of type III and IV secretion, progress in the
      analysis of bacterial interactions with host phagocytes has been extensive but
      largely focused on the macrophage. The remarkable growth of information about
      bacterial subversion of macrophage metabolism has been summarized in several
      excellent reviews. The scope of progress on neutrophil-bacteria interactions is
      more limited and dominated by recent studies of the granulocyte pathogen,
      Anaplasma phagocytophilum, the agent of granulocytic ehrlichiosis. SUMMARY: For
      many pathogens, contact with or ingestion by phagocytes elicits a vigorous but
      varied microbial response. The response repertoire includes activation of type
      III and type IV secretion systems that inject effector molecules into the host
      cell. Effectors modify host cell signaling and metabolic pathways to favor
      survival of the microbe. Whereas microbial secretory structures are few in kind
      and relatively conserved, effector molecules are numerous and variable. Effectors
      may promote phagocytosis by nonphagocytic cells or suppress phagocytosis by
      macrophages and neutrophils. They may suppress assembly or misdirect localization
      of the phagocyte NADPH oxidase that is responsible for generating toxic oxidants,
      and they may suppress phagosome-lysosome fusion. Phagocytosed bacteria may also
      up-regulate the expression of defensive proteins that attenuate the effects of
      phagocyte-derived antimicrobial toxins. These pathogenic stratagems probably have
      their origins in the competition among single-celled organisms, eukaryotes versus
      prokaryotes, that arose early in evolution.

PMID- 14676622
TI  - Nitric oxide signaling: systems integration of oxygen balance in defense of cell
      integrity.
AB  - PURPOSE OF REVIEW: Nitric oxide has emerged as a ubiquitous signaling molecule
      subserving diverse pathophysiologic processes, including cardiovascular
      homeostasis and its decompensation in atherogenesis. Recent insights into
      molecular mechanisms regulating nitric oxide generation and the rich diversity of
      mechanisms by which it propagates signals reveal the role of this simple gas as a
      principle mediator of systems integration of oxygen balance. RECENT FINDINGS: The
      molecular lexicon by which nitric oxide propagates signals encompasses the
      elements of posttranslational modification of proteins by redox-based
      nitrosylation of transition metal centers and free thiols. Spatial and temporal
      precision and specificity of signal initiation, amplification, and propagation
      are orchestrated by dynamic assembly of supramolecular complexes coupling nitric
      oxide production to upstream and downstream components in specific subcellular
      compartments. The concept of local paracrine signaling by nitric oxide over
      subcellular distances for short durations has expanded to include endocrine-like
      effects over anatomic spatial and temporal scales. From these insights emerges a
      role for nitric oxide in integrating system responses controlling oxygen supply
      and demand to defend cell integrity in the face of ischemic challenge. In this
      context, nitric oxide coordinates the respiratory cycle to acquire and deliver
      oxygen to target tissues by regulating hemoglobin function and vascular smooth
      muscle contractility and matches energy supply and demand by down-regulating
      energy-requiring functions while shifting metabolism to optimize energy
      production. SUMMARY: Insights into mechanisms regulating nitric oxide production
      and signaling and their integration into responses mediating homeostasis place
      into specific relief the role of those processes in pathophysiology. Indeed,
      endothelial dysfunction associated with altered production of nitric oxide
      regulating tissue integrity contributes to the pathogenesis underlying
      atherogenesis. Moreover, this central role in pathophysiology identifies nitric
      oxide signaling as a key target for novel therapeutic interventions to minimize
      irreversible tissue damage associated with ischemic cardiovascular disease.

PMID- 14676623
TI  - Cytoskeletal remodeling in leukocyte function.
AB  - PURPOSE OF REVIEW: This review focuses on recent developments in understanding
      the roles and regulation of the cytoskeleton in the function of leukocytes.
      RECENT FINDINGS: New studies have shed light on the regulation and dynamics of
      actin and microtubules in leukocytes relevant both to cell motility generally and
      to immune function specifically. The roles of cytoskeletal dynamics in processes
      such as cell activation, cell migration, and phagocytosis are being elucidated.
      Dramatic progress has been made recently in understanding the mechanisms of
      leukocyte directional sensing, polarization, and chemotaxis. SUMMARY: Leukocytes
      need to be activated, polarize, change shape, move, or phagocytose in response to
      their environment. Leukocytes accomplish these processes by remodeling their
      cytoskeleton, the active musculoskeletal system of the cell that is not just the
      ultimate effector of motile responses but is also a dynamic framework for
      subcellular organization and regional signaling. Active areas of research include
      the direct and indirect reciprocal interactions between the cytoskeleton and the
      membrane and among cytoskeletal elements. The pervasive and multi-layered roles
      played by small GTPases of the Rho family and phosphoinositides in leukocyte
      function are also becoming clearer.

PMID- 14676624
TI  - Modeling the dosage effect of oncogenes in leukemogenesis.
AB  - PURPOSE OF REVIEW: This review discusses the dosage effects of some oncogenes in
      leukemogenesis and compares various methods that model human hematologic
      malignancies in mice by introducing genetic lesions in a cell type-specific, time
      controlled, and dosage-relevant manner. RECENT FINDINGS: Recent evidence
      indicates that optimal dosage of cancer-related gene products plays an important
      role in the induction of mouse tumors that recapitulate their human counterparts.
      SUMMARY: The mouse is a very valuable model system for experimentally dissecting
      the in vivo pathogenesis of cancer, for identifying pharmacological targets of
      cancer and for evaluating cancer therapies. In modeling human cancer, it has been
      shown that both the timing of introducing/activating oncogenic mutation(s) and
      the cell types into which the genetic lesion(s) is targeted are critical for
      cancer development. Recent studies also showed that efficient induction of
      relevant human leukemia in mice by certain oncogenes, such as PML/RARalpha and
      TEL/ABL, only occurred when they were expressed at a low level or close to
      pathophysiologically relevant level. These studies stress the importance of
      studying oncoprotein function at pathophysiologically relevant expression levels.
      Conditional gene expression systems are powerful tools for developing mouse
      models for human cancer by introducing genetic lesions in a cell type-specific,
      time-controlled and dosage-relevant manner. The bone marrow retroviral
      transduction and transplantation system can also mimic the cell and temporally
      specific origin of hematological malignancies by targeting oncogenes into sorted
      hematopoietic cells. This versatile approach is particularly powerful in
      structure-function analysis of oncogenes in vivo. However, overexpression of a
      transgene driven by retroviral vectors may alter the biological outcomes of the
      transgene in vivo. My colleagues and I have shown that generating vectors with
      modulated transgene expression can overcome this limitation of the retroviral
      transduction system in modeling human cancer in mice. Conditional gene expression
      and the modified retroviral transduction systems will be complimentary in
      studying human cancers in mice.

PMID- 14676625
TI  - Mechanisms and implications of imatinib resistance mutations in BCR-ABL.
AB  - PURPOSE OF REVIEW: Aside from bone marrow transplantation, a definitive cure for
      Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) has yet to
      be developed. Although Imatinib, the first molecularly targeted drug developed
      for CML has achieved a remarkable success, the emergence of resistance to this
      agent mitigates the prospect of a cure for this leukemia. Though a variety of
      resistance mechanisms can arise, in the majority of patients resistance coincides
      with reactivation of the tyrosine kinase activity of the BCR-ABL fusion
      oncoprotein. This can result from gene amplification and, more importantly, point
      mutations that disrupt the bind of imatinib to BCR-ABL itself. In this review, we
      aim to define and illuminate mechanisms of resistance and describe how drug
      resistance is shedding new light on kinase domain regulation. RECENT FINDINGS: In
      light of recent studies and publications, it is now clear that Imatinib exerts
      its inhibitory action by stabilizing the inactive non ATP-binding conformation of
      BCR-ABL and that mutations even outside the kinase domain can lead to enhanced
      autophosphorylation of the kinase, thereby stabilizing the active conformation
      that resists imatinib binding. So far, 25 different substitutions of 21 amino
      acid residues of BCR-ABL have been detected in CML patients. In addition, it has
      been recently illustrated that mutations preexist the onset of treatment and that
      some confer a more aggressive disease phenotype. Finally it has been shown that
      molecular remission is almost never reached through Imatinib therapy. SUMMARY:
      The most common mechanism of relapse for CML patients treated with Imatinib is
      the appearance of point mutations in the BCR-ABL oncogene that confer resistance
      to this drug. Insights into the emerging problem of resistance should promote the
      rational development of alternative, synergistic, and potentially curative
      treatment strategies.

PMID- 14676626
TI  - SHP-2 and myeloid malignancies.
AB  - PURPOSE OF REVIEW: This review focuses on the non-receptor Src-homology 2 domain
      containing protein tyrosine phosphatase SHP-2 and its role in signal
      transduction, hematopoiesis, and leukemogenesis. Specifically, we discuss the
      role of inherited and somatic mutations that result in SHP-2 gain-of-function in
      human disease, including myeloid malignancies. RECENT FINDINGS: Up-regulation of
      RAS signaling is a major perturbation that drives the aberrant growth of
      malignant myeloid cells. Leukemia-associated SHP-2 mutations define a novel type
      of molecular events resulting in hyperactive RAS function. SUMMARY: SHP-2 plays
      an important role in intracellular signaling elicited by growth factors,
      hormones, and cytokines, and it is required during development and hematopoiesis.
      Gain of function mutations in PTPN11, the gene encoding SHP-2, is observed in
      Noonan syndrome and related development disorders, as well as in myeloid
      malignancies. Fully characterizing the incidence and spectrum of PTPN11 mutations
      in hematologic malignancies, and in other forms of cancer, is an area of active
      investigation.

PMID- 14676627
TI  - The FIP1L1-PDGFRalpha kinase in hypereosinophilic syndrome and chronic
      eosinophilic leukemia.
AB  - PURPOSE OF REVIEW: The idiopathic hypereosinophilic syndrome is a rare
      hematologic disorder characterized by sustained unexplained eosinophilia with
      associated end-organ damage and by a striking male predominance. The first
      insights into the molecular etiology of this heterogeneous disease were obtained
      from a "bedside-to-bench" approach. Successful empiric treatment of patients with
      the hypereosinophilic syndrome with the selective tyrosine kinase inhibitor
      imatinib mesylate (Gleevec, Novartis) ultimately led to the discovery of the
      FIP1L1-PDGFRalpha fusion kinase in about half of the hypereosinophilic syndrome
      cases. RECENT FINDINGS: The FIP1L1-PDGFRA fusion gene is generated by a cryptic
      interstitial chromosomal deletion, del(4)(q12q12), which indicates that these
      cases are clonal hematopoietic malignancies and should be reclassified as chronic
      eosinophilic leukemias based on current World Health Organization
      recommendations. In addition, the FIP1L1-PDGFRA fusion gene was also identified
      in cases with systemic mast cell disease. In vitro and in vivo studies confirmed
      that FIP1L1-PDGFRalpha is a therapeutic target of imatinib, forming a rational
      basis for the treatment of FIP1L1-PDGFRA positive chronic eosinophilic leukemia
      and mastocytosis with imatinib. Similar to BCR-ABL-positive leukemias, resistance
      to imatinib due to point mutations in the PDGFRalpha kinase domain may develop.
      We have explored strategies to circumvent resistance to imatinib using
      alternative tyrosine kinase inhibitors such as PKC412. SUMMARY: The discovery of
      the FIP1L1-PDGFRA fusion gene in the hypereosinophilic syndrome is an example of
      the power of clinical translational research and identifies interstitial
      chromosomal deletion as a novel mechanism to generate oncogenic tyrosine kinase
      fusion genes.

PMID- 14676628
TI  - Clinical, genetic, and therapeutic insights into systemic mast cell disease.
AB  - PURPOSE OF REVIEW: Mast cell disease is markedly heterogeneous in its underlying
      molecular pathogenesis, clinical presentation, natural history, and specific
      treatment. Skin-only disease (cutaneous mastocytosis) is infrequent in adults and
      systemic mastocytosis may be broadly classified as an indolent or aggressive
      variant based on the absence or presence of impaired organ function. Urticaria
      pigmentosa and mast cell mediator release symptoms can occur in all categories of
      mast cell disease and may not be prognostically detrimental. The purpose of this
      review is to summarize current concepts and recent advances in the pathogenesis
      and treatment of adult mast cell disease. RECENT FINDINGS: A series of laboratory
      investigations has revealed that mast cell disease is a clonal stem cell
      disorder, and at least two genes (c-kit and PDGFRA) with pathogenetically
      relevant mutations have been identified. FIP1L1-PDGFRA+ mast cell disease
      responds completely to imatinib mesylate. Both Asp816Val c-kit+ and molecularly
      undefined cases have been shown to respond to 2-chlorodeoxyadenosine therapy
      after failing treatment with interferon-alpha. SUMMARY: A partial molecular
      classification of mast cell disease is now possible; Asp816Val c-kit+, FIP1L1
      PDGFRA+, and molecularly undefined cases. Such molecular classification is
      therapeutically relevant.

PMID- 14676629
TI  - Role of CD44 and hyaluronic acid (HA) in activation of alloreactive and antigen
      specific T cells by bone marrow-derived dendritic cells.
AB  - In the current study, the role played by hyaluronic acid (HA) and its receptor
      CD44 on the activation and functions of dendritic cells (DCs) was investigated.
      Activation of DCs with HA enhanced their ability to stimulate allogeneic and
      antigen (Ag)-specific T cells markedly. HA treatment upregulated the expression
      of costimulatory molecules such as CD40, CD80, and CD86 on DCs. Cell mixing
      experiments using DC or T cells from CD44 wild-type or CD44 knockout mice as well
      as blocking studies with anti-CD44 monoclonal antibodies revealed that CD44
      expression on T cells but not DC played a critical role in Ag-specific T-cell
      responsiveness. Also, the HA-induced activation of DC was independent of CD44.
      When conjugate formation between Ag-pulsed DCs and Ag-specific T cells was
      studied, the deficiency of CD44 on T cells rather than on DCs was found to play a
      key role in T-cell-DC interaction. Together, these data demonstrated that HA can
      activate DC independently of CD44; however, CD44 expressed on Ag-specific T cells
      plays a critical role in its interaction with DC and resultant expansion of T
      cells.

PMID- 14676630
TI  - Prostate tumor microenvironment alters immune cells and prevents long-term
      survival in an orthotopic mouse model following flt3-ligand/CD40-ligand
      immunotherapy.
AB  - A novel orthotopic metastatic model of mouse prostate cancer was developed using
      MHC-negative TRAMP-C1P3 (transgenic adenocarcinoma of mouse prostate) cells
      derived by serial passage of the parental TRAMP-C1 line in mouse prostate glands.
      TRAMP-C1P3 cells grew efficiently in mouse prostate glands and reproducibly
      metastasized to draining lymph nodes. Using this model, we show that Fms-like
      tyrosine kinase-3 ligand (flt3-L) dramatically inhibited growth of preexisting
      orthotopic TRAMP-C1P3 tumors and the development of metastatic disease. Mice
      remained in remission for several months following termination of flt3-L
      treatment but eventually relapsed and died of progressive disease. flt3-ligand
      treatment induced a pronounced mixed inflammatory cell infiltrate that consisted
      of CD8alpha-CD4- dendritic cells (CD11c+), macrophages, granulocytes (Gr-1+) and
      to a lesser extent T cells (CD4+ and CD8+). Dendritic cells isolated from TRAMP
      C1P3 tumors were phenotypically immature (CD11c+ B7.2-I-A-CD40-), and this
      phenotype was also predominant in peripheral organs of mice treated with flt3-L
      alone or in combination with the DC maturation factor, CD40-L. Diminished
      expression of TCR-beta, CD3-epsilon, and CD3-zeta was also observed on
      intratumoral T cells, although these signaling proteins were reexpressed
      following in vitro culture with IL-2. The TCR/CD3 complex remained intact on
      peripheral T cells except in mice treated with flt3-L where CD3-zeta loss was
      observed. In contrast to alphabeta-T cells, tumor-infiltrating gammadelta-T cells
      maintained expression of their antigen receptors but not CD3epsilon. Thus, TRAMP
      C1P3 tumors quickly establish a microenvironment that profoundly diminishes
      expression of molecules critical for normal dendritic cell and T cell function,
      thus limiting the efficacy of flt3-L and CD40-L immunotherapy. Overall, these
      data suggest that long-term cures of established MHC-negative tumors may not be
      achieved until therapeutic interventions are engineered to overcome this
      immunosuppressive microenvironment.

PMID- 14676631
TI  - Freeze-thawing procedures have no influence on the phenotypic and functional
      development of dendritic cells generated from peripheral blood CD14+ monocytes.
AB  - Little is known about the potential influence of cryopreservation on the biologic
      activities of dendritic cells (DCs). In this study, we examined the effects of
      freeze-thawing on the phenotypic and functional development of human DCs obtained
      from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood
      CD14+ cells. CD14+ cells were cultured, immediately or after freeze-thawing, with
      granulocyte-macrophage CSF and interleukin-4 for 9 days, and then with added
      tumor necrosis factor-alpha for another 3 days. For both fresh and freeze-thawed
      monocytes, immature DCs harvested on day 6 and mature DCs harvested on day 9 of
      culture were examined under the same conditions. Cells were compared with regard
      to their 1) capacities for antigen endocytosis and chemotactic migration
      (immature DCs), and 2) allogeneic mixed lymphocyte reaction and antigen-specific
      cytotoxic T lymphocyte responses (mature DCs). Freeze-thawing did not affect the
      viability or subsequent maturation of DCs at any stage of development.
      Furthermore, essentially no difference was observed in phenotype or function
      between cells generated from fresh or cryopreserved/thawed cells. Although this
      study design was limited with the use of fetal bovine serum, the observation
      still suggests that freeze-thawing does not affect viability, phenotype,
      subsequent maturation, or functions of DCs at any stage of maturation.

PMID- 14676632
TI  - Phenotypic and functional maturation of tumor antigen-reactive CD8+ T lymphocytes
      in patients undergoing multiple course peptide vaccination.
AB  - Successful immunotherapy with peptide vaccines depends on the in vivo generation
      of sufficient numbers of anti-tumor T cells with appropriate phenotypic and
      functional characteristics to mediate tumor destruction. Herein, we report the
      induction of high frequencies of circulating CD8+ T cells (4.8% to 38.1%)
      directed against the native gp100:209-217 peptide derived from the gp100 melanoma
      melanocyte tumor antigen in five HLA-A*0201 patients at high risk of recurrence
      of melanoma after multiple courses of immunization with modified gp100:209
      217(210M) peptide in IFA. Longitudinal peripheral blood mononuclear cell (PBMC)
      analysis revealed a phenotypic shift of native peptide-specific CD8+ T cells from
      an early effector to an effector memory (CD27- CD28- CD62L- CD45RO+) phenotype
      with repeated immunizations and functional maturation that correlated with
      gp100:209-217 peptide-specific T-cell precursor frequencies. Postimmunization
      PBMC exhibited direct ex vivo recognition of melanoma cell lines in ELISPOT
      analysis, showed lytic capability against peptide-pulsed target cells, and
      proliferated in response to native peptide stimulation. One year after final
      immunization, circulating vaccine-specific CD8+ T cells persisted in patients'
      PBMC with a maintained effector memory phenotype. The results herein demonstrate
      the efficacy of a multiple course peptide-immunization strategy for the
      generation of high frequencies of tumor antigen-specific T cells in vivo, and
      further show that continued peptide immunization results in the escalating
      generation of functionally mature, tumor-reactive effector memory CD8+ T
      lymphocytes.

PMID- 14676633
TI  - Immunological monitoring of patients with melanoma after peptide vaccination
      using soluble peptide/HLA-A2 dimer complexes.
AB  - To facilitate the immunologic monitoring of a peptide vaccine trial, a novel,
      empty dimeric HLA-A2 molecule (A2 dimer) that could be loaded with peptides was
      produced. The dimer comprises the extracellular domain of HLA-A2 noncovalently
      linked to a fusion protein consisting of human beta2-microglobulin joined to the
      human IgG1 Fc domain. Peptide-loaded dimer complexes were used to assess the
      function of peptide-specific T cells. HLA-A2 gp100 peptide dimers stimulated
      interferon (IFN)-gamma production by the gp100-specific TIL-1520 cell line.
      Gp100/A2 dimer stimulation in combination with intracellular cytokine staining
      was used to analyze peptide-specific T-cell responses in patients with melanoma
      after vaccination with the modified gp100: 209-2M peptide in adjuvant. Titration
      analysis of the amount of peptide-loaded dimer required to stimulate gp100
      specific T cells was used to estimate the functional avidity of effector/memory
      CD8+ T lymphocytes. The number of peptide-specific T cells detected in the
      peripheral blood of vaccinated patients using this assay was comparable to the
      number determined by staining with fluoresceinated gp100: 209-2M HLA-A2
      tetramers. IFN-gamma production by T cells was comparable after stimulation with
      peptide-pulsed dimers, T2 cells, or autologous dendritic cells. Peptide-loaded A2
      dimers could also be used directly to stimulate T cells in the ELISPOT assay.

PMID- 14676634
TI  - Vaccination with predesignated or evidence-based peptides for patients with
      recurrent gynecologic cancers.
AB  - Two different trials of peptide vaccination were conducted for patients with
      recurrent gynecologic cancers. In the first regimen, four HLA-A24+ patients (two
      with cervical cancer and two with ovarian cancer) were vaccinated with peptides
      that were predesignated before vaccination. Three patients exhibited with a grade
      1 adverse effect, and no clinical response was observed in any patients. In the
      second regimen, six HLA-A24+ and four HLA-A2+ patients (five with cervical
      cancer, one with endometrial cancer, one with uterine sarcoma, and three with
      ovarian cancer) were vaccinated with peptides (maximum four) to which preexisting
      cytotoxic T lymphocyte precursors in the periphery were confirmed before
      vaccination. With this regimen, grade 1 adverse effects were observed in eight
      patients, a grade 2 adverse effect in one patient, and a grade 3 adverse effect
      (ie, rectal bleeding) in one patient. However, this regimen was able to enhance
      peptide-specific cytotoxic T lymphocytes in seven of ten patients, and three of
      five cervical cancer patients showed objective tumor regression. Analysis of
      immunoglobulin G -reactive to administered peptides suggested that the induction
      of peptide-specific immunoglobulin G was correlated with clinical responses.
      Overall, these results suggest that peptide vaccination of patients showing
      evidence of preexisting peptide-specific cytotoxic T lymphocyte precursors could
      be superior to vaccination with predesignated peptides, and that the evidence
      based regimen is applicable for clinical trials in treatment of patients with
      recurrent gynecologic cancers.

PMID- 14676635
TI  - High frequency of melanoma-associated antigen or HLA class I loss does not
      correlate with survival in primary melanoma.
AB  - Melanoma-associated antigens are at the center of many immunotherapeutic trials
      in melanoma. Little is known about the impact of antigen expression on the
      natural course of disease. We stained 110 cases of primary melanoma with a median
      follow-up of 13 years (range 10-18 years) for melanoma-associated antigens gp100,
      MelanA/MART-1, MAGE-3, tyrosinase, and for HLA class I molecules. Of 91 cases
      evaluated, we found immunoreactivity for gp100, MelanA/MART-1, and tyrosinase in
      88%, 80%, and 87% of primary tumors, respectively, for MAGE-3 in 37% and for HLA
      class I in 86% of primary tumors. Loss, that is, heterogeneous expression within
      primary tumors, was most pronounced for gp100 (73% of primary tumors) and least
      for MAGE-3 (27% of primary tumors). MelanA/MART-1 and tyrosinase expression loss
      was 58% and 59% of primary tumors, respectively. There was a high rate of
      expression loss for HLA class I (74%). Univariate and multivariate statistical
      analysis of expression in primary tumors and loss of melanoma antigens as well as
      HLA class I in individual primary tumors showed no significant correlation to
      overall survival. Loss of gp100 and loss of tyrosinase expression showed a
      negative survival trend over homogeneous expression of these antigens, although
      not reaching statistical significance (P = 0.08 and P = 0.09, respectively). We
      conclude that loss of melanoma antigen expression as well as HLA class I
      expression is a frequent observation in primary melanoma. However, no
      statistically significant correlation between loss of these antigens in
      individual primary tumors and negative impact on overall survival was found in
      our cohort.

PMID- 14676636
TI  - The spectrum of apocrine lesions of the breast.
AB  - Apocrine change is seen in a wide spectrum of breast lesions, ranging from
      microscopic cysts to invasive carcinoma. This article reviews the range of
      apocrine lesions and discusses the clinical significance of these lesions.
      Although apocrine change in many cases does not present any diagnostic
      difficulty, apocrine proliferations demonstrating cytologic atypia can be
      particularly challenging. The histologic criteria that have been proposed to
      foster reproducibility in categorizing such lesions are reviewed. This review
      attempts to clarify the terminology that has been applied to a range of benign
      lesions, including sclerosing adenosis and complex sclerosing lesions, containing
      foci of apocrine change. Malignant apocrine lesions, including both in situ and
      invasive carcinoma, are also discussed.

PMID- 14676637
TI  - Gonadal teratomas: a review and speculation.
AB  - Teratomas of the ovary and testis are confusing because, despite histologic
      similarities, they exhibit different biologic behaviors, depending mostly on the
      site of occurrence and the age of the patient. Thus, most ovarian teratomas are
      benign, and most testicular teratomas are malignant, with the exception of those
      occurring in children. These general statements, however, do not hold true for
      ovarian teratomas that are "immature" or exhibit "malignant transformation" and
      for dermoid and epidermoid cysts of the testis, categories of ovarian and
      testicular teratomas that are malignant and benign, respectively. This review
      concentrates on some of the "newer" observations concerning these interesting and
      confusing neoplasms, including diagnostically deceptive patterns. It is the
      author's opinion that much of the confusion regarding gonadal teratomas can be
      clarified by the concept that the usual ovarian teratoma derives from a benign
      germ cell in a parthenogenetic-like fashion, whereas the typical postpubertal
      testicular example derives from a malignant germ cell, mostly after evolution of
      that originally malignant cell to an invasive germ cell tumor (ie, embryonal
      carcinoma, yolk sac tumor, etc). The postpubertal testicular teratomas can
      therefore be thought of as an end-stage pattern of differentiation of a malignant
      germ cell tumor. The pediatric testicular teratomas, as well as dermoid and
      epidermoid cysts of the testis, however, must derive from benign germ cells, in a
      fashion similar to most ovarian teratomas. The teratomatous components of mixed
      germ cell tumors of the ovary, on the other hand, likely have a pathogenesis
      similar to that of postpubertal testicular teratomas.

PMID- 14676638
TI  - Fine needle aspiration biopsy of soft tissue sarcomas: utility and diagnostic
      challenges.
AB  - The role of fine needle aspiration biopsy (FNAB) as the primary modality for the
      initial diagnosis of previously undiagnosed soft tissue sarcomas presents several
      important challenges. Most practicing pathologists are inexperienced with the
      wide array of soft tissue neoplasms and their morphologic heterogeneity, making
      them susceptible to misdiagnosis. However, in the hands of experienced
      cytopathologists, FNAB in conjunction with ancillary techniques has a diagnostic
      accuracy approaching 95% for the diagnosis of malignancy. FNAB has been shown to
      have a diagnostic yield nearly identical with core needle biopsy while avoiding
      significant clinical complications. Nevertheless, FNAB has certain limitations
      related to the accurate histologic grading and subtyping of certain subgroups of
      sarcomas. It may also be difficult to accurately distinguish between low-grade
      sarcomas and benign or borderline cellular lesions, especially in the spindle
      cell sarcoma subgroup. The aim of this review is to highlight the utility and
      limitations of FNAB in the primary diagnosis of soft tissue sarcomas, highlight
      diagnostically challenging lesions, and comment on the limitations of FNAB in
      providing a "definitive" diagnosis.

PMID- 14676639
TI  - Histopathologic changes in metabolic bone disease.
AB  - Metabolic bone disease encompasses a heterogeneous group of disorders that
      influence skeletal metabolism and structure. They are generally diagnosed at an
      advanced stage and manifest clinically with stunted skeletal growth in children
      and pathologic fractures in adults. Biochemical markers for bone metabolism are
      equivocal and microscopic examination of labeled bone remains the gold standard
      for the diagnosis and accurate monitoring of the response to therapy. This
      article reviews the role of microscopic bone changes in the diagnosis and
      management of metabolic bone disease.

PMID- 14676640
TI  - Dysproteinemia and the kidney.
AB  - Dysproteinemia is a clinical state characterized by abnormal, often excessive,
      synthesis of immunoglobulin (Ig) molecules or subunits. Dysproteinemia results
      from clonal proliferation of plasma cells or B lymphocytes. The abnormal
      circulating Ig molecules or subunits (most commonly free light chains) reach the
      glomerulus via the systemic circulation and are associated with the development
      of a variety of pathologic lesions within the kidney. Free light chain molecules
      may pass through the glomerular basement membrane and form casts within distal
      tubular lumina (myeloma cast nephropathy) or form crystals within the cytoplasm
      of proximal tubules (light chain Fanconi syndrome). Alternatively, Ig molecules
      or subunits may form paraprotein tissue deposits and produce an array of
      pathologic lesions, most commonly amyloidosis and monoclonal Ig deposition
      disease. The pattern of renal parenchymal disease is determined by the unique
      properties of the Ig molecule or subunit. Each of the patterns of renal disease
      is in turn associated with unique, but frequently overlapping, clinical features
      and outcomes. This review emphasizes the pathologic, clinical, and prognostic
      differences among the patterns of renal parenchymal disease related to
      dysproteinemia.

PMID- 14676641
TI  - Pathology and the internet.

PMID- 14676643
TI  - On the other side of the door.

PMID- 14676644
TI  - Terrorism: a public health threat with a trauma system response.
AB  - BACKGROUND: The threat of mass casualties and widespread infectious disease
      caused by terrorism is now a challenge for our government and public health
      system. Funds have been granted to the states by the Centers for Disease Control
      and Prevention and the Health Resources and Services Administration to establish
      bioterrorism preparedness and response capabilities. METHODS: Hartford Hospital
      has been designated as a Center of Excellence for Bioterrorism Preparedness by
      the Commissioner of the Connecticut Department of Public Health. The Center of
      Excellence has implemented strategies to prepare for a possible bioterrorist
      attack. A unique model that combines epidemiology and traumatology is being used
      to guide the preparedness activities. Although the focus of the grant from the
      Connecticut Department of Public Health is bioterrorism, the application of the
      model can apply to preparation for all terrorist events. RESULTS: Implementation
      of strategies indicates that bioterrorism preparedness is well underway. Similar
      initiatives should be achievable by other trauma systems throughout the country.
      CONCLUSION: A Center of Excellence for Bioterrorism Preparedness in Connecticut
      is successfully modifying a trauma system to meet the challenge of a new public
      health threat, terrorism.

PMID- 14676645
TI  - Distribution and care of shipboard blast injuries (USS Cole DDG-67).
AB  - On October 12, 2000, the destroyer USS Cole was anchored in a foreign port and
      was severely damaged by explosives in a small craft adjacent to the ship at the
      port side waterline. Seventeen crew members were killed in the incident. The
      wounded were evacuated to several medical facilities for their initial care and
      then to the military hospital in Landstuhl, Germany, and subsequently to the
      Charette Health Care Center (Naval Medical Center) in Portsmouth, Virginia. There
      were 35 surviving patients who had sustained 81 total injuries associated with
      the explosion. The distribution of the injuries included orthopedic,
      ophthalmologic, soft tissue, otolaryngologic, burns, inhalation, and other
      miscellaneous injuries. Twenty-seven of the patients were discharged after 24
      hour observation. This article reviews the distribution of injuries found in the
      fatalities and the wounded crew members and the subsequent care required to
      prepare the military medical community for potential future incidents of this
      type.

PMID- 14676646
TI  - Mild head injuries: impact of a national strategy for implementation of
      management guidelines.
AB  - BACKGROUND: A national survey in 1996 showed insufficient routines for management
      of patients with mild head injuries in Norwegian hospitals. Since then, the
      Scandinavian Guidelines for Management of Mild Head Injuries have been published.
      METHODS: A cross-sectional questionnaire survey of management practice was
      performed in all 59 hospitals in 2002. We compared the results with figures from
      1996 and evaluated guideline compliance. RESULTS: The proportion of noncompliant
      hospitals was reduced (p = 0.02) from 52% to 31%. The proportion assessing the
      patient's level of consciousness according to the Glasgow Coma Scale increased (p
      = 0.001) from 49% to 80%. The proportion requiring a normal computed tomographic
      scan if a patient with a history of loss of consciousness was to be sent home
      from the accident and emergency department increased (p < 0.001) from 1 (2%) to
      13 (19%). CONCLUSION: The Scandinavian Guidelines for Management of Mild Head
      Injuries have had a significant impact on management practice in Norwegian
      hospitals.

PMID- 14676647
TI  - Hyperglycemia and outcomes from pediatric traumatic brain injury.
AB  - BACKGROUND: The clinical significance of hyperglycemia after pediatric traumatic
      brain injury is controversial. This study addresses the relationship between
      hyperglycemia and outcomes after traumatic brain injury in pediatric patients.
      METHODS: We identified trauma patients admitted during a single year to our
      regional pediatric referral center with head regional Abbreviated Injury Scale
      scores > or = 3. We studied identified patients for admission characteristics
      potentially influencing their outcomes. The primary outcome measure was Glasgow
      Outcome Scale score. RESULTS: Patients who died had significantly higher
      admission serum glucose values than those patients who survived (267 mg/dL vs.
      135 mg/dL; p = 0.000). Admission serum glucose > or = 300 mg/dL was uniformly
      associated with death. Admission Glasgow Coma Scale score (odds ratio, 0.560; 95%
      confidence interval, 0.358-0.877) and serum glucose (odds ratio, 1.013; 95%
      confidence interval, 1.003-1.023) are independent predictors of mortality in
      children with traumatic head injuries. CONCLUSION Hyperglycemia and poor
      neurologic outcome in head-injured children are associated. The pathophysiology
      of hyperglycemia in neurologic injury after head trauma remains unclear.

PMID- 14676648
TI  - Blood pressure and outcome after severe pediatric traumatic brain injury.
AB  - BACKGROUND: The relationship between systolic blood pressure and outcome in
      children after severe traumatic brain injury (TBI) is unclear. We examined the
      relationship between age-appropriate systolic blood pressure (AASBP) percentile
      and outcome after severe pediatric TBI. METHODS: We examined the association
      between AASBP percentiles and outcome in 172 children younger than 14 years of
      age with a Glasgow Coma Scale score < 9. Outcome was evaluated using discharge
      Glasgow Outcome Scale score. Poor outcome was defined as a Glasgow Outcome Scale
      score < 4. RESULTS: Poor outcome was associated with AASBP < 75th percentile
      (odds ratio, 4.2; 95% confidence interval, 2.1-8.3). Patients with systolic blood
      pressure (SBP) > or = 90 mm Hg and AASBP < 75th percentile had a higher odds for
      poor outcome compared with patients with SBP > or = 90 mm Hg and AASBP > or =
      75th percentile (odds ratio, 3.5; 95% confidence interval, 1.7-7.3). CONCLUSION
      AASBP < 75th percentile was associated with poor outcome after severe pediatric
      TBI, even when SBP was > or = 90 mm Hg.

PMID- 14676649
TI  - Violence-related traumatic brain injury: a population-based study.
AB  - BACKGROUND: Most studies of traumatic brain injury (TBI) and violence are small,
      focus on one violent mechanism only, and are nonrepresentative. This large,
      population-based effort examines characteristics, circumstances of injury,
      treatment pathways, and outcomes of persons with TBI as a result of all types of
      violence, compares them with other TBI survivors, identifies a risk profile, and
      examines how a violent cause impacts later outcomes. METHODS: This study involved
      medical record abstraction and telephone survey at 1 year postinjury of a
      weighted sample of 2,771 Coloradans hospitalized with TBI between January 1,
      1996, and June 30, 1999. RESULTS: People with violently incurred TBI are more
      likely to be young, male, members of minority groups, single, and premorbid
      alcohol abusers than other TBI survivors. At 1 year postinjury, they report less
      community integration and more headaches, confusion, and sensory and attentional
      disturbances. Predictors of these outcomes included age, gender, injury severity,
      and employment status. CONCLUSION: It appears that essentially the same factors
      that increase risk of sustaining a violent TBI negatively impact later outcomes
      as well.

PMID- 14676650
TI  - Mild hypothermia reduces expression of heat shock protein 60 in leukocytes from
      severely head-injured patients.
AB  - BACKGROUND: Infectious complications are among the most serious problems that
      occur in severely head-injured patients treated with mild hypothermia. The
      mechanism underlying the susceptibility to infection has not been clarified. Heat
      shock protein (HSP) 60 has been reported to play an essential role in innate
      immunity. Thus, we conducted a study to clarify the impact of mild hypothermia on
      the expression of HSPs in polymorphonuclear leukocytes (PMNLs) in severely head
      injured patients. METHODS: Between September 1997 and November 1999, 17 severely
      head-injured patients with a Glasgow Coma Scale score of 8 or less at admission
      in whom intracranial pressure could be maintained below 20 mm Hg by conventional
      therapy were randomly assigned to two treatment groups: a mild hypothermia group
      (HT group, nine patients) and a normothermia group (NT group, eight patients).
      The HT group was subjected to mild hypothermia (intracranial temperature, 34
      degrees C) for 48 hours followed by rewarming at a rate of 1 degrees C per day
      for 3 days, whereas the NT group was subjected to normothermia (intracranial
      temperature, 37 degrees C) for 5 days. Blood samples were serially obtained at
      three time points; days 0 to 1, days 2 to 5, and days 6 to 14 after head injury.
      We measured the expression of HSP27, HSP60, HSP70, and HSP90 by flow cytometry.
      RESULTS: The two groups were similar with respect to prognostic factors, and
      there was no difference in clinical outcome. The expression of PMNL HSP60 in the
      HT group was significantly lower in all three time periods compared with that in
      the NT group (p < 0.05), whereas expression of the other HSPs did not differ
      significantly between the groups. The incidence of infectious complications was
      significantly increased in the HT group over that in the NT group (p < 0.05). In
      in vitro studies, PMNLs from 10 healthy volunteers were incubated at 37 degrees
      C, 34 degrees C, or 26 degrees C for 1 hour with sodium arsenite (100
      micromol/L), an HSP inducer. The expression of HSP60 at 26 degrees C and 34
      degrees C was significantly lower than that at 37 degrees C (p < 0.05), whereas
      expression of the other HSPs did not differ significantly at 26 degrees C, 34
      degrees C, or 37 degrees C. CONCLUSION: Mild hypothermia reduces the expression
      of HSP60 in PMNLs from severely head-injured patients. Thus, mild hypothermia may
      suppress innate immunity.

PMID- 14676651
TI  - Clinical efficacy of serial computed tomographic scanning in severe closed head
      injury patients.
AB  - BACKGROUND: The purpose of this study was to determine whether serial computed
      tomographic (CT) scans of the head serve to prompt operative intervention. After
      the initial and 24- to 48-hour repeat scans, if no operative intervention has
      been performed, further serial scans are ordered on a planned basis or on the
      basis of changes in clinical status. METHODS: This study is a retrospective
      review from January 1996 to December 2000. Results of the initial, follow-up, and
      serial CT scans were recorded for the 51 patients who met the inclusion/exclusion
      criteria. RESULTS: One hundred seventeen (53.4%) serial CT scans were ordered. No
      urgent operative interventions were performed on the basis of the serial CT
      scans. Three scans (2.56%) led to nonurgent neurosurgical intervention.
      CONCLUSION: In severe head-injured patients who are nonneurosurgical candidates
      on the basis of initial and repeat CT scans, serial head CT scans have little
      clinical efficacy and do not lead to urgent operative intervention.

PMID- 14676652
TI  - Isolated brain injury as a cause of hypotension in the blunt trauma patient.
AB  - BACKGROUND: Emerging evidence suggests that, contrary to standard teaching,
      isolated brain injury may be associated with hypotension. This study sought to
      determine the frequency of isolated brain injury-induced hypotension in blunt
      trauma victims. METHODS: Hypotensive adult trauma patients were categorized
      according to the cause of hypotension: hemorrhagic (hemoglobin < 11.0),
      neurogenic, isolated brain, or other. Their clinical data and outcomes were
      compared. RESULTS: The cause of hypotension was hemorrhagic in 113 (49%),
      isolated brain injury in 30 (13%), neurogenic in 14 (6%), and other causes in 24
      (10%). Fifty (22%) were indeterminate. Hemorrhagic, isolated brain, and
      neurogenic groups were similar in age, Injury Severity Score, and systolic blood
      pressure. The Glasgow Coma Scale score of the isolated brain group was lower than
      in the hemorrhagic group (4.4 vs. 8.4, p < 0.05). Mortality was higher in the
      isolated brain group compared with the hemorrhagic group (80% vs. 50%, p < 0.05)
      and in the subgroup of hemorrhagic patients with versus without associated brain
      injury (57% vs. 39%, p < 0.05). CONCLUSION: Isolated brain injuries account for
      13% of hypotensive events after blunt trauma and are associated with an increased
      mortality compared with hemorrhage-induced hypotension. In hypotensive brain
      injured patients, hemorrhagic sources should be excluded rapidly, and the focus
      should be on resuscitation.

PMID- 14676653
TI  - Traumatic spinal cord injury in Ontario, Canada.
AB  - BACKGROUND: Few population-based analyses of spinal cord injuries exist from
      which to base Canadian prevention initiatives. This study aimed to calculate
      rates of traumatic spinal cord injury for the province of Ontario and describe
      these injuries by several epidemiologic parameters. METHODS: Two thousand three
      hundred eighty-five hospital admissions were studied for April 1, 1994, through
      March 31, 1999. RESULTS: Annual age-standardized rates declined from a maximum of
      46.2 hospitalizations per 1 million population (95% confidence interval, 42.1
      50.3) to 37.2 per 1 million (95% confidence interval, 33.8-41.0). Male rates
      declined over the study period, whereas female rates remained stable. Leading
      external causes included unintentional falls (1,030 of 2,385 [43.2%]), especially
      among the elderly, and transport injuries (1,021 of 2,385 [42.8%]), especially
      among those aged less than 40 years. Intentional injuries were most commonly seen
      among those aged 20 to 39 years (48 of 86 [55.8%]). Misclassification of some
      elder fall cases as spinal cord injuries is a methodologic concern. CONCLUSION:
      The results indicate the relative importance of several external causes of injury
      and are useful in establishing rational priorities for prevention.

PMID- 14676654
TI  - Angiographic embolization for liver injuries: low mortality, high morbidity.
AB  - OBJECTIVE: Angiographic embolization (AE) is a safe and effective method for
      controlling hemorrhage in both blunt and penetrating liver injuries. Improved
      survival after hepatic injuries has been documented using a multimodality
      approach; however, patients still have significant long-term morbidity. This
      study examines further the role of AE in both blunt and penetrating liver
      injuries and the outcomes of its use. METHODS: The medical records of 37
      consecutive patients admitted from 1995 to 2002 to a Level I trauma center who
      underwent hepatic angiography with the intent to embolize were reviewed.
      Demographic and clinical information including Injury Severity Score, length of
      stay, mortality, intra-abdominal complications, admission physiologic variables,
      and the number and type of abdominal operations performed were collected.
      RESULTS: Thirty-seven patients underwent hepatic angiography and 26 patients had
      hepatic embolization performed. Eleven patients underwent early-AE, immediately
      after computed tomographic scanning, and 15 underwent late-AE, after liver
      related operations or later in their hospital course. There was a 27% mortality
      rate overall. There were 11 liver-related complications in the 26 embolizations.
      Excluding the early deaths, the associated morbidity was 58%, which included
      hepatic necrosis, hepatic abscesses, and bile leaks. CONCLUSION: There is
      increasing adjunctive use of AE in patients managed both operatively and
      nonoperatively. Intra-abdominal complications are common in these salvaged
      patients with severe liver injuries. Those patients that underwent early-AE
      received significantly fewer blood transfusions and more commonly had sterile
      hepatic collections. Only 26% of patients required liver-related surgery after
      AE. Therefore, the integration of AE as an adjunctive modality for patients with
      high-grade liver injuries is a safe and effective therapeutic option.

PMID- 14676655
TI  - Prediction of mortality in pediatric trauma patients: new injury severity score
      outperforms injury severity score in the severely injured.
AB  - BACKGROUND: The Injury Severity Score (ISS) is a widely accepted method of
      measuring severity of traumatic injury. A modification has been proposed--the New
      Injury Severity Score (NISS). This has been shown to predict mortality better in
      adult trauma patients, but it had no predictive benefit in pediatric patients.
      The aim of this study was to determine whether the NISS outperforms the ISS in a
      large pediatric trauma population. METHODS: Admissions in the National Pediatric
      Trauma Registry between April 1996 and September 1999 were included. The ISS and
      NISS were calculated for each patient. The study endpoints were mortality at
      hospital discharge, functional outcome in three domains (expression, locomotion,
      and feeding), and discharge disposition for the survivors. Predictive ability of
      each score was assessed by area under the receiver operating characteristic
      curve. RESULTS: The NISS and ISS performed equally well at predicting mortality
      in patients with lower injury severity (ISS < 25), but the NISS was significantly
      better at predicting mortality in the more severely injured patients. Both scores
      performed equally well at predicting expression and feeding ability. The NISS was
      superior to the ISS in predicting locomotion ability at discharge. Thirty-seven
      percent of patients had an NISS that was higher than their ISS. These patients
      had a significantly higher mortality and suffered worse functional outcomes.
      CONCLUSION: The NISS performs as well as the ISS in pediatric patients with lower
      injury severity and outperforms the ISS in those with higher injury severity.

PMID- 14676656
TI  - Phagocyte priming as a prognostic indicator in the intensive care unit.
AB  - BACKGROUND: The purpose of this study was to study the temporal changes in
      circulating phagocyte respiratory burst activity and its relationship to
      mortality in intensive care unit (ICU) patients. METHODS: Thirty-seven
      consecutive patients over a 3-week period were studied on their first, third, and
      seventh day of admission to the regional ICU in Northern Ireland. Blood samples
      were assayed for respiratory burst activity using luminol-enhanced whole blood
      chemiluminescence. RESULTS: Compared with survivors, nonsurvivors exhibited
      significantly higher Acute Physiology and Chronic Health Evaluation II scores, a
      base deficit, and reduced phagocyte activity (median [interquartile range])
      (24.00% [18.00%, 56.00%] vs. 38.00% [30.00%, 63.50%], p = 0.047, Mann-Whitney U
      test) on day 3 of admission to the ICU. CONCLUSION: Temporal changes in phagocyte
      activation dependent on the underlying insult were seen in ICU patients.
      Furthermore, the degree of phagocyte activation was able to distinguish between
      survivors and nonsurvivors on day 3 of admission to the ICU. Nonsurvivors
      exhibited reduced phagocyte activation, suggesting patients at risk of mortality
      exhibit systemic anergy.

PMID- 14676657
TI  - Changing patterns in the management of penetrating abdominal trauma: the more
      things change, the more they stay the same.
AB  - BACKGROUND: Damage control surgery (DCS) and treatment of abdominal compartment
      syndrome have had major impacts on care of the severely injured. The objective of
      this study was to see whether advances in critical care, DCS, and recognition of
      abdominal compartment syndrome have improved survival from penetrating abdominal
      injury (PAI). METHODS: The care of 250 consecutive patients requiring laparotomy
      for PAI (1997-2000) was reviewed retrospectively. Organ injury patterns,
      survival, and use of DCS and its impact on outcome were compared with a similar
      experience reported in 1988. RESULTS: Two hundred fifty patients had a positive
      laparotomy for PAI. Twenty-seven (10.8%) required abdominal packing and 45
      (17.9%) did not have fascial closure. Seven (2.8%) required emergency department
      thoracotomy and 21 (8.4%) required operating room thoracotomy. Two hundred
      seventeen (86.8%) survived overall. Small bowel (47.2%), colon (36.4%), and liver
      (34.4%) were most often injured. Mortality was associated with the number of
      organs injured (odds ratio, 1.98; 95% confidence interval, 1.65-2.37; p < 0.001).
      Vascular injury was a risk factor for mortality (p < 0.001), as was need for DCS
      (p < 0.001), emergency department thoracotomy (p < 0.001), and operating room
      thoracotomy (p < 0.001). Seventy-nine percent of deaths occurred within 24 hours
      from refractory hemorrhagic shock. DCS was used in 17.9% (n = 45) versus 7.0% (n
      = 21) in 1988, with a higher survival rate (73.3% vs. 23.8%, p < 0.001). DCS was
      associated with significant morbidity including sepsis (42.4%, p < 0.001), intra
      abdominal abscess (18.2%, p = 0.009), and gastrointestinal fistula (18.2%, p <
      0.001). CONCLUSION: Penetrating abdominal organ injury patterns and survival from
      PAI have remained similar over the past decade. Death from refractory hemorrhagic
      shock in the first 24 hours remains the most common cause of mortality. DCS and
      the open abdomen are being used more frequently with improved survival but result
      in significant morbidity.

PMID- 14676658
TI  - Hemoglobin-based oxygen carrier provides heterogeneous microvascular oxygenation
      in heart and gut after hemorrhage in pigs.
AB  - BACKGROUND: In this study, the hypothesis was tested that resuscitation with
      hemoglobin-based oxygen carriers (HBOCs) affects the oxygenation of the
      microcirculation differently between and within organs. To this end, we tested
      the influence of the volume of an HBOC on the microcirculatory oxygenation of the
      heart and the gut serosa and mucosa in a porcine model of hemorrhage. METHODS: In
      anesthetized open-chested pigs (n = 24), a controlled hemorrhage (30 mL/kg over 1
      hour) was followed by resuscitation with 10, 20, or 30 mL/kg diaspirin
      crosslinked hemoglobin (DCLHb) or isovolemic resuscitation with 30 mL/kg of a 6%
      hydroxyethyl starch solution (HAES). Measurements included systemic and regional
      hemodynamic and oxygenation parameters. Microvascular oxygen pressures (microPO2)
      of the epicardium and the serosa and mucosa of the ileum were measured
      simultaneously by the palladium-porphyrin phosphorescence technique. Measurements
      were obtained up to 120 minutes after resuscitation. RESULTS: After hemorrhage, a
      low volume of DCLHb restored both cardiac and intestinal microPO2. Resuscitation
      of gut microPO2 with a low volume of DCLHb was as effective as isovolemic
      resuscitation with HAES. Higher volumes of DCLHb did not restore cardiac
      microPO2, as did isovolemic resuscitation with HAES, but increased gut microPO2
      to hyperoxic values, dose-dependently. Effects were similar for the serosal and
      mucosal microPo2. In contrast to a sustained hypertensive effect after
      resuscitation with DCLHb, effects of DCLHb on regional oxygenation and
      hemodynamics were transient. CONCLUSION: This study showed that a low volume of
      DCLHb was effective in resuscitation of the microcirculatory oxygenation of the
      heart and gut back to control levels. Increasing the volume of DCLHb did not
      cause an additional increase in heart microPO2, but caused hyperoxic
      microvascular values in the gut to be attained. It is concluded that
      microcirculatory monitoring in this way elucidates the regional behavior of
      oxygen transport to the tissue by HBOCs, whereas systemic variables were
      ineffective in describing their response.

PMID- 14676659
TI  - Paradoxical cytoskeleton and microparticle formation changes in monocytes and
      polymorphonuclear leukocytes in severe systemic inflammatory response syndrome
      patients.
AB  - BACKGROUND: Circulating monocytes and polymorphonuclear leukocytes (PMNLs) are
      considered as central regulators controlling systemic inflammatory response after
      severe insults. Recently, activated monocytes and PMNLs have been reported to
      produce microparticles (MPs) in vitro. The objective of this study was to
      evaluate production of MPs and changes of cytoskeleton in monocytes from severe
      systemic inflammatory response syndrome (SIRS) patients, and to compare them with
      those in PMNLs. METHODS: Twenty severe SIRS patients (SIRS criteria and serum C
      reactive protein > 10 mg/dL) and 15 healthy volunteers were included. MP
      formation and F-actin content in monocytes and PMNLs were measured by flow
      cytometry in the presence or absence of lipopolysaccharide or formylmethionyl
      leucyl-phenylalanine (FMLP). The membrane expression of human leukocyte antigen
      DR and CD64 in monocytes and O2- production in PMNLs were also measured by flow
      cytometry. RESULTS: In severe SIRS patients, MP formation with and without
      lipopolysaccharide in monocytes significantly decreased in comparison with those
      in normal controls (p < 0.05), whereas those with and without FMLP in PMNLs
      increased (p < 0.05). F-actin content with and without FMLP in monocytes also
      significantly decreased in patients (p < 0.05), whereas those in PMNLs increased
      as compared with normal controls (p < 0.05). The expression of human leukocyte
      antigen-DR in monocytes significantly decreased in patients (p < 0.05), which
      indicated monocyte modulation. The O2- production in PMNLs increased in patients
      (p < 0.05), which showed PMNL activation. CONCLUSION: The changes of MP formation
      and cytoskeleton in circulating monocytes and PMNLs were paradoxically different
      in severe SIRS patients.

PMID- 14676660
TI  - Elevated intramuscular compartment pressures do not influence outcome after
      tibial fracture.
AB  - BACKGROUND: Although the importance of monitoring differential compartment
      pressures (Delta P) after tibial fractures has been established, many surgeons
      continue to use intramuscular pressures in diagnosing compartment syndrome,
      despite the limitations of this strategy. The cited reason for this is concern
      over leaving high intramuscular pressures untreated. METHODS: One hundred one
      patients with tibial fractures with satisfactory Delta P were studied. Forty-one
      patients had elevated intramuscular pressures of over 30 mm Hg for more than 6
      hours continuously. These patients were compared with a control group of 60
      patients who had pressures of less than 30 mm Hg throughout. Outcome was measured
      prospectively in terms of muscular power and return to function over the year
      after injury. RESULTS: No significant differences were found. CONCLUSION:
      Provided Delta P remains satisfactory, patients with elevated intramuscular
      pressures after tibial fracture do not have a greater incidence of complications
      than those with low pressures. These patients can therefore be observed safely.

PMID- 14676661
TI  - The effect of divergent screw placement on the initial strength of plate-to-bone
      fixation.
AB  - BACKGROUND: Numerous implants exist that allow screws to be placed at varying
      angles for lag fixation or to fix additional fragments. This study determined how
      placing screws at different angles affects fixation strength. METHODS: Using a
      bone model, we first investigated the pullout strength of screws inserted at
      varying angles; then, we studied the strength of plate-bone constructs with end
      screws placed at divergent angles. RESULTS: Varying the screw angle from 0 to 10
      to 20 degrees progressively weakened the screw pullout resistance. No additional
      decrease was found in varying the angle further. In contrast, the strength of
      fixation of plate to bone was higher for constructs with screws placed at 20 or
      30 degrees off of perpendicular when tested in gap-open bending and axial
      compression (all p < 0.05). No such differences were found in torsion.
      CONCLUSION: The pullout strength with angled screws is reduced, but this does not
      translate into reduced strength of the bone-to-plate interface.

PMID- 14676662
TI  - Multiple trauma and scapula fractures: so what?
AB  - BACKGROUND Scapula fractures are rare and are presumed to indicate severe
      underlying trauma. We studied injury patterns and overall outcome in patients
      with multiple injuries with scapula fractures. METHODS: We carried out a
      retrospective review of patients with multiple injuries (Injury Severity Score
      [ISS] > or = 16) with chest and musculoskeletal injuries admitted to our
      institution between 1993 and 1999 to investigate whether the presence of a
      scapula fracture is a marker of increased morbidity and mortality. RESULTS: There
      were 1,164 patients admitted with multiple trauma. Seventy-nine (6.8%) of the
      1,164 sustained a scapula fracture, forming the study group. The remainder of the
      patients (n = 1,085) formed the control group of the study. Both groups of
      patients were similar with regard to age and Glasgow Coma Scale score (age, 42 +/
      17.8 [+/- SD] vs. 40 +/- 22; GCS score, 11.2 +/- 5.1 vs. 11 +/- 5 in the study
      and control groups, respectively). The overall ISS was significantly higher in
      those with scapula fractures (27.12 +/- 15.13 vs. 22.8 +/- 14.4, p = 0.01).
      Patients with scapula fractures also had more severe chest injuries (Abbreviated
      Injury Scale score of 3.46 +/- 1.1 vs. 3.1 +/- 1.0, respectively), but not
      significantly so. However, the incidence of rib fractures was significantly
      higher in the patients with scapula fractures (p < 0.05). The incidence and
      severity of head and abdominal injuries were similar in the two groups. The
      severity of extremity injuries in patients with scapula fractures was
      significantly lower (2.4 +/- 0.6 vs. 2.7 +/- 0.7, p = 0.001). The rate of
      admission, the length of intensive care unit stay, and the overall length of
      hospital stay were similar in the two groups. The overall mortality rate was
      11.4% in patients with scapula fractures and 20% in those without scapula
      fractures (p = 0.1). CONCLUSION: Patients with scapula fractures have more severe
      underlying chest injuries and overall ISS. However, this did not correlate with a
      higher rate of intensive therapy unit admission, length of hospital stay, or
      mortality.

PMID- 14676663
TI  - Evaluation of a cleanser for petroleum-contaminated skin.
AB  - BACKGROUND: Extremity injuries contaminated with petroleum products pose clinical
      dilemmas. This project was designed to evaluate the efficacy of a dioctyl
      sulfosuccinate (DS) solution for cleansing petroleum-contaminated skin. METHODS:
      One hundred Sprague-Dawley rats were subjected to a contamination protocol
      followed by a cleansing procedure. Four petroleum contaminants and five cleansing
      solutions were selected. The protocol consisted of shaving, initial punch biopsy,
      contamination, precleansing punch biopsy, standardized scrub protocol, and
      postcleansing punch biopsy. Biopsy samples were analyzed for petroleum residue
      using fluorometry. RESULTS: The 10% DS solution had the highest reduction of
      crude oil, grease, and tar: 99.6 +/- 0.4% (mean +/- SD) contaminant reduction for
      crude oil, 99.8 +/- 0.2% for grease, and 99.8 +/- 0.2% for tar. The other
      cleansers showed less efficacy (p < 0.05). CONCLUSION: Concentrated DS appears to
      be significantly more effective at cleaning petroleum products from skin than the
      commonly chosen surgical and commercial cleansers.

PMID- 14676664
TI  - Prospective evaluation of combined suprapubic and urethral catheterization to
      urethral drainage alone for intraperitoneal bladder injuries.
AB  - BACKGROUND: The role of suprapubic catheterization after repair of
      intraperitoneal bladder injury is controversial and has been found to be
      superfluous in retrospective studies. We sought to evaluate bladder drainage
      prospectively. METHODS: Patients were prospectively enrolled and were assigned to
      suprapubic catheter drain after bladder repair or urethral catheter alone
      determined by the unit admitting the patient. Factors that were evaluated were
      associated injuries, hospital stay, duration of catheterization, and catheter
      related complications. RESULTS: There were 42 patients: there were 39 male
      patients, and the mean age was 29.6 years. The patients were matched for age and
      associated injuries. The morbidity (p = 0.004) and hospital stay (p = 0.028) were
      significantly higher in the suprapubic drainage group. CONCLUSION: Urethral
      catheterization is adequate to effect bladder drainage after intraperitoneal
      bladder injury. In addition, it is associated with a shorter hospital stay and
      lower morbidity.

PMID- 14676665
TI  - Vacuum-assisted wound closure achieves early fascial closure of open abdomens
      after severe trauma.
AB  - BACKGROUND: This study reviews the efficacy of vacuum-assisted wound closure
      (VAWC) to obtain primary fascial closure of open abdomens after severe trauma.
      METHODS: The study population included shock resuscitation patients who had open
      abdomens treated with VAWC. The VAWC dressing was changed at 2- to 3-day
      intervals and downsized as fascial closure was completed with interrupted suture.
      The Trauma Research Database and the medical records were reviewed for pertinent
      data. RESULTS: Over 26 months, 35 patients with open abdomens were managed by
      VAWC. Six died early, leaving 29 patients who were discharged. Of these, 25 (86%)
      were successfully closed using VAWC at a mean of 7 +/- 1 days (range, 3-18 days).
      Of the four patients that failed VAWC, two developed fistulas. No patients
      developed evisceration, intra-abdominal abscess, or wound infection. CONCLUSION:
      VAWC achieved early fascial closure in a high percentage of open abdomens, with
      an acceptable rate of complications.

PMID- 14676666
TI  - The prevalence of venous thromboembolism of the lower extremity among thermally
      injured patients determined by duplex sonography.
AB  - BACKGROUND: Morbidity and mortality from venous thromboembolism (VTE) remains a
      significant problem for hospitalized patients. Despite the ample prospective
      literature defining the prevalence of VTE in hospitalized patient populations,
      the prevalence of VTE in the thermally injured population remains largely
      unknown. METHODS: We prospectively studied 148 thermally injured patients with
      hospital stays of greater than 3 days with lower extremity duplex ultrasonograms
      obtained at admission and discharge. RESULTS: Nine patients experienced VTE
      (6.08%). Eight of the nine deep venous thromboses were proximal. One of the two
      pulmonary embolisms was fatal. Treatment risk factors that were associated with
      VTE were the presence of a central venous line (p = 0.020) and transfusion of
      more than 4 units of packed red blood cells (p = 0.023). These treatment factors
      were significantly related to each other (p < 0.0001), to body surface area
      burned, and to intervention. CONCLUSION: The prevalence of VTE in burn patients
      is similar to that of moderate- to high-risk general surgical patients for whom
      VTE prophylaxis is recommended. VTE prophylaxis of burn patients, especially
      those requiring central venous lines and more than 4 units of packed red blood
      cells, should be considered.

PMID- 14676667
TI  - Inferior vena caval injury with intramural thrombosis after penetrating trauma:
      case report and review of the literature.

PMID- 14676668
TI  - Guglielmi detachable coils embolization of a penetrating vertebral artery injury:
      a case report.

PMID- 14676669
TI  - Preoperative diagnosis of traumatic disruption of the hepatocolic ligament by
      computed tomographic scanning: an interesting case of hemoperitoneum.

PMID- 14676670
TI  - Penetrating head injury caused by bear claws: case report.

PMID- 14676671
TI  - Aortic dissection after blunt trauma.

PMID- 14676672
TI  - Oligosymptomatic aortic dissection: diagnostic implications and pitfalls.

PMID- 14676673
TI  - Re: Endotracheal intubation in the field does not improve outcome in trauma
      patients who present without an acutely lethal traumatic brain injury. Bochicchio
      GV, Ilahi O, Joshi M, Bochicchio K, Scalea TM. J.Trauma. 2003;54:307-11.

PMID- 14676674
TI  - An alternative treatment option for management of zone III wounds of the internal
      jugular vein.

PMID- 14676675
TI  - Cerebral fat embolism: an indication for ICP monitor?

PMID- 14676676
TI  - Role of C5a-C5aR interaction in sepsis.
AB  - C5a-C5aR signaling plays an essential role in innate immunity of neutrophils.
      However, excessive interaction of C5a-C5aR results in harmful effects in these
      cells. In sepsis, robust generation of C5a occurs; blockade of either C5a or C5aR
      greatly improves survival in experimental sepsis following cecal ligation and
      puncture (CLP). The beneficial effects derived from C5a-C5aR interaction are
      associated with preservation of neutrophil innate immune functions (chemotaxis,
      phagocytosis, respiratory burst), attenuation of the inflammatory reaction,
      amelioration of coagulopathy, alteration in adhesion molecule expression, and
      modulation of apoptosis. Following CLP, C5aR expression is significantly elevated
      in organs, perhaps setting the stage for C5a-induced organ dysfunction. In
      contrast, C5aR content on neutrophils drops significantly at early stages of
      sepsis and progressively increases at later time points. Re-expression of C5aR on
      neutrophils during sepsis appears to be associated with the functional recovery
      of neutrophil innate immune functions. Following CLP, there is a positive
      correlation between C5aR content on blood neutrophils and survival of individual
      animals; high levels of C5aR on neutrophils are associated with survival, whereas
      low levels of C5aR on neutrophils predict mortality. These data suggest that in
      sepsis C5a-C5aR signaling is excessive, resulting in paralysis of neutrophil
      function. Interception of either C5a or C5aR dramatically improves survival
      during experimental sepsis.

PMID- 14676677
TI  - Endogenous cannabinoids are candidates for lipid mediators of bone cement
      implantation syndrome.
AB  - Acute hypotension, hypoxemia, cardiac arrhythmias, cardiac arrest, (or a
      combination of these), and sudden death are well-recognized complications of the
      cemented hip arthroplasty procedure. Collectively, these are known as the bone
      cement implantation syndrome (BCIS). The endogenous cannabinoids, anandamide
      (ANA) and 2-arachidonylglycerol (2-AG), are reported to be strong vasodilators
      and play a role in the hypotension associated with hemorrhagic and septic shock.
      In the present study, a potential role for the endogenous cannabinoids in
      influencing hemodynamic variables in BCIS was investigated. Thirty-five patients
      (35 hips) entered a prospective, randomized clinical trial. The patients were
      divided into two groups. Group 1 comprised 16 patients who had the component
      inserted using a conventional cementing technique, whereas group 2 consisted of
      19 patients who had the femoral component inserted without cement. Blood samples
      were taken at six consecutive time points: before anesthesia, after reaming the
      femur, 2 min after insertion of stems with or without cement into the femur, and
      10 min, 20, and 30 min after stem insertion. In group 1 (with cement), the mean
      levels of ANA and 2-AG significantly increased after stem insertion. In a
      comparison of each group after stem insertion, mean ANA and 2-AG levels in group
      1 also significantly differed from those in group 2. By contrast, in group 2
      (without cement) neither ANA nor 2-AG levels exhibited a significant increase or
      change at any point in time. In conclusion, we have shown for the first time that
      endogenous cannabinoids are candidates for lipid mediators of BCIS.

PMID- 14676678
TI  - Serum derived from multiple trauma patients promotes the differentiation of
      endothelial progenitor cells in vitro: possible role of transforming growth
      factor-beta1 and vascular endothelial growth factor165.
AB  - Ischemia in various organs and tissues takes place during and as a direct result
      of multiple trauma (MT). Bone marrow-derived endothelial progenitor cells (EPCs)
      are involved in neovascularization after ischemic incidences. Here, we report
      that serum derived from patients with MT stimulates differentiation of EPCs in
      vitro from peripheral blood mononuclear cells (PBMCs). EPCs were identified by
      DiL-Acetyl-LDL-uptake with concomitant UEA-I-lectin binding. A significant
      increase in EPC numbers was noted when PBMCs were cultivated for 72 h with the
      serum of MT patients (n = 25) obtained at 5 days. Furthermore, serum from MT
      patients enhanced the functional acting of EPCs to form prevascular structures in
      matrigel. Reverse transcription polymerase chain reaction analysis revealed gene
      expression of transforming growth factor (TGF)-beta1- and vascular endothelial
      growth factor (VEGF) receptors 1 and 2. Reverse transcription polymerase chain
      reaction analysis was based on further cultivated cell preparations, which
      contained at least 80% EPCs. Moreover, the addition of recombinant VEGF or low
      concentrations of TGF-beta increased EPC differentiation. In addition,
      neutralization of TGF-beta1 and of VEGF165 in MT serum using specific antibodies
      resulted in a significant decrease in EPC differentiation. Our data indicate that
      TGF-beta1 and VEGF165 play a pivotal role for EPC differentiation induced by
      serum of polytrauma patients.

PMID- 14676679
TI  - Humane endpoints in shock research.
AB  - In biomedical research using animal models, the phrase "humane endpoints" refers
      to predetermined criteria used to judge when the research animals should be
      humanely euthanized. The intended goal of humane endpoints is to minimize the
      distress or suffering of research animals; however, if applied incorrectly, this
      well-intended concept could lead to premature decisions and inaccurate data,
      resulting in a waste of animal life. A concensus on specific endpoints for shock
      and inflammation research is not available but several biochemical, physical and
      behavioral parameters have been suggested for other research models. In addition,
      the authors have found, in the studies presented here, that increasing body
      weight, decreased body temperature, and inability to ambulate are important
      parameters in a model of cecal ligation and puncture. However, it is clear that
      the applicability of these endpoints may change with the model of disease,
      intensity of insults, experimental treatments and other factors. Consequently,
      humane endpoints should be assigned cautiously and preferably after preliminary
      studies to prevent aberrant research results. In order to accomplish this,
      investigators must become aware of certain concepts including: when to implement
      endpoints, what endpoints to consider, and how to establish the endpoints for
      their studies. Equipped with the basic principles of humane endpoints,
      investigators can make informed decisions that meet current standards of animal
      care while still achieving the scientific goals of their research studies.

PMID- 14676680
TI  - Development of a sensitive microarray immunoassay and comparison with standard
      enzyme-linked immunoassay for cytokine analysis.
AB  - Cytokine and cytokine inhibitors represent important components of the
      inflammatory response in patients with trauma, shock, and sepsis. Many
      investigators wish to quantify cytokines and it would be advantageous to measure
      multiple cytokines in a multiplex manner to obtain an inflammatory profile rather
      than a single value. Using the well-accepted standard enzyme-linked immunoassay
      (ELISA) as a basis, a microarray immunoassay (MI) was designed to measure 16
      different human cytokines simultaneously. The MI was performed by spotting
      antibodies on nitrocellulose pads affixed to glass slides. Detection of the
      mediators was performed with biotin-conjugated antibodies followed by
      fluorescently labeled streptavidin. All antibodies and other reagents were
      purchased commercially. The MI achieved a lower limit of detection that was
      generally similar to traditional ELISAs (approximately 4-12 pg/mL) and also had a
      similar coefficient of variation. In the multiplexed MI, there was no cross
      reactivity between mediators. To verify the utility of the MI, cytokines and
      cytokine inhibitors were measured in endotoxin stimulated human blood by both
      ELISA and MI. Virtually identical cytokine concentrations were measured by both
      methods. These results describe the development of a sensitive, specific and cost
      effective multiplexed microarray immunoassay that produces values similar to
      traditional ELISAs.

PMID- 14676681
TI  - Hemodynamic and cardiac contractile function during sepsis caused by cecal
      ligation and puncture in mice.
AB  - Sepsis is among the leading causes of death in the critically ill, yet the
      pathophysiology of sepsis is incompletely understood. Genetically engineered mice
      offer a unique opportunity to explore the cellular and molecular pathogenesis of
      sepsis. However, the hemodynamic responses of mice during sepsis are not
      completely understood because of the difficulty in performing cardiovascular
      measurements in mice. We used a 1.4-F pressure and conductance catheter to
      measure hemodynamics in wild-type C57BL/6J mice during sepsis caused by cecal
      ligation and puncture. Septic mice exhibited significant hypothermia compared
      with the sham group. In addition, there was a progressive decrease in mean
      arterial blood pressure and systemic vascular resistance in septic mice as well
      as an increase in stroke volume and cardiac output. Sepsis also caused a
      significant time-dependent impairment of left ventricular function as indicated
      by decreased dp/dtmax and dp/dtmin. The slope of end systolic pressure volume
      relationship also decreased over time, as did the time varying maximum elastance
      and preload-recruitable stroke work of the left ventricle. In conclusion, septic
      mice exhibit hemodynamic alterations during sepsis that are similar to those
      observed in humans. The miniaturized conductance catheter allows for effective
      measurements of hemodynamic function in septic mice and provides measurements
      that cannot be obtained using other cardiovascular monitoring techniques.

PMID- 14676682
TI  - Calpain inhibitor I reduces intestinal ischemia-reperfusion injury in the rat.
AB  - In this study we evaluated the effect of calpain inhibitor I on splanchnic artery
      occlusion (SAO) shock-mediated injury. SAO shock was induced in rats by clamping
      both the superior mesenteric artery and the celiac trunk for 45 min. After 1 h of
      reperfusion, SAO-shocked rats developed a significant fall in mean arterial blood
      pressure. Western blot analysis of ileum revealed a marked decrease in of IkappaB
      alpha expression, and immunohistochemical examination of necrotic ileum
      demonstrated a marked increase in the immunoreactivity to P-selectin,
      intracellular adhesion molecule (ICAM-1), nitrotyrosine formation, and nuclear
      enzyme poly[adenosine diphosphate (ADP)-ribose] synthase (PARS) activation. An
      increase in myeloperoxidase activity (143 +/- 22 4.5 U/100 mg wet tissue vs. 4.5
      +/- 2.5 U/100 mg wet tissue of sham-operated rats) and in malondialdehyde levels
      (13.12 +/- 1.2 micromol/100 mg wet tissue vs. 3.9 +/- 1.1 micromol/100 mg wet
      tissue of sham-operated rats) was also observed in rats subjected to ischemia
      reperfusion injury. Calpain inhibitor I, given intraperitoneally 30 min before
      ischemia at a dose of 15 mg/kg, significantly improved mean arterial blood
      pressure, markedly reduced IkappaB-alpha degradation and the intensity of P
      selectin and ICAM-1 in the reperfused ileum. Calpain inhibitor I also
      significantly prevented neutrophil infiltration (32.95 +/- 9.82 U/100 mg wet
      tissue), reduced malondialdehyde levels (6.76 +/- 0.98 micromol/100 mg wet
      tissue) and markedly improved the histological status of the reperfused tissue.
      In conclusion, this study demonstrates that calpain inhibitor I exerts multiple
      protective effects in splanchnic artery occlusion-reperfusion shock and suggests
      that calpain inhibitor I may be a candidate for consideration as a therapeutic
      intervention for ischemia-reperfusion injury.

PMID- 14676683
TI  - Effect of a novel thromboxane A2 inhibitor on right ventricular-arterial coupling
      in endotoxic shock.
AB  - We investigated the effects of a dual thromboxane (TX)A2 synthase inhibitor and
      TXA2 receptor antagonist (BM-573) on right ventricular-arterial coupling in a
      porcine model of endotoxic shock. Thirty minutes before the onset of 0.5 mg/kg
      endotoxin infusion, six pigs (Endo group) received an infusion with a placebo
      solution, and six other pigs (Anta group) with BM-573. Right ventricular pressure
      volume loops were obtained by the conductance catheter technique. The slope (Ees)
      of the end-systolic pressure-volume relationship and its volume intercept at 25
      mmHg were calculated as measures of right ventricular systolic function. RV
      afterload was quantified by pulmonary arterial elastance (Ea), and Ees/Ea ratio
      represented right ventricular-arterial coupling. Mechanical efficiency was
      defined as the ratio of stroke work and pressure-volume area. In this model of
      endotoxic shock, BM-573 blunted the early phase of pulmonary hypertension,
      improved arterial oxygenation, and prevented a decrease in right ventricular
      myocardial efficiency and right ventricular dilatation. However, the drug could
      not prevent the loss of homeometric regulation and alterations in right
      ventricular-arterial coupling. In conclusion, dual TXA2 synthase inhibitor and
      receptor antagonists such as BM-573 have potential therapeutic applications,
      improving right ventricular efficiency and arterial oxygenation in endotoxic
      shock.

PMID- 14676684
TI  - Burn-induced gut mucosal homeostasis in TCR delta receptor-deficient mice.
AB  - Gammadelta T lymphocytes make up approximately 50% of lymphocytes in the
      intestine. These cells have been shown to prime macrophages for TNF-alpha
      production after burn. We previously showed that neutralizing anti-TNF-alpha
      antibodies reduce mucosal atrophy by decreasing gut epithelial apoptosis after
      severe burn. We hypothesized that burn-induced mucosal turnover is diminished in
      T cell receptor delta gene knockout (TCR delta-/-) mice through diminished TNF
      alpha activity. Forty-two wild-type and 42 TCR delta-/- mice (C57-BL6) were
      randomly assigned to burn and sham burn groups. The burn group underwent a 25%
      total body surface area (TBSA) scald burn. The proximal small intestine was
      harvested at 2, 12, and 48 h. To assess mucosal atrophy, mucosal height and cell
      numbers in the villi and crypts were determined on hematoxylin and eosin-stained
      tissue sections. Apoptotic gut epithelium was identified by terminal deoxyuridine
      nick-end labeling (TUNEL) staining, and cell proliferation was detected by
      immunostaining for proliferative cell nuclear antigen (PCNA). TNF-alpha mRNA
      expression was measured by RT-PCR. Caspase-8 activity was measured by
      colorimetric assay. Statistical analysis was performed with two-way analysis of
      variance and t testing. Significance was accepted at P < 0.05. Data are expressed
      as means +/- SEM. TNF-alpha mRNA expression was significantly decreased in TCR
      delta-/- mice at 2 h after burn. Gut epithelial apoptosis and proliferation in
      both wild-type and TCR delta-/- mice were significantly increased after burn, but
      TCR delta-/- mice had a significantly lower levels of apoptosis (P < 0.01) and
      proliferation (P < 0.05) when compared with wild-type mice. Burn-induced mucosal
      atrophy was identified in groups by decreasing villus height, crypt depth, and
      villus and crypt cell number (P < 0.001) compared with sham, but no difference
      was found between wild-type and TCR delta-/- mice. Caspase-8 activity was
      significantly diminished in TCR delta-/- mice compared with wild-type mice.
      Gammadelta T cells are associated with increased TNF-alpha expression and gut
      epithelial turnover in the small bowel after severe burn. However, absence of
      delta T cell receptor did not inhibit mucosal atrophy after severe burn. This
      study suggests that gut mucosal atrophy after severe burn is a multifactorial
      process associated with increased TNF-alpha activity.

PMID- 14676685
TI  - Tissue energetics as measured by nuclear magnetic resonance spectroscopy during
      hemorrhagic shock.
AB  - The defect in energy production in an organism during shock states may be related
      to the impairment of mitochondrial respiration early in shock. The aim of this
      study was to investigate the timing and degree of cellular energetic changes
      during hemorrhagic shock in real time. Instrumented, splenectomized swine were
      randomized to undergo hemorrhagic shock, induced by a 35% blood volume bleed, for
      90 min with (n = 10) or without (n = 9) subsequent resuscitation. Resuscitated
      animals received shed blood in two increments followed by two normal saline
      boluses (20 mL/kg/bolus). Throughout experimentation, tissue phosphoenergetics of
      liver and skeletal muscle were monitored using 31P nuclear magnetic resonance
      (NMR) spectroscopy via NMR coils on the liver and hindlimb. Near-infrared
      spectroscopy probes were used to measure liver, stomach, and skeletal muscle
      oxyhemoglobin saturation (StO2). Hemorrhagic shock induced an increase in
      phosphomonoesters in skeletal muscle (baseline: 7.09%, 90 min: 9.94% (P < 0.05);
      expressed as percent total phosphorus). This increase resolved in animals
      receiving resuscitation (n = 10) but remained elevated in those in unresuscitated
      shock (n = 9). Inorganic phosphate levels increased and betaATP levels decreased
      significantly in the liver of animals in shock as compared with baseline. StO2 in
      skeletal muscle, stomach, and liver correlated with whole organism oxygen
      delivery (r2 = 0.356, 0.368, and 0.432, respectively). We conclude that
      hemorrhagic shock induces early elevation of phosphomonoesters in skeletal
      muscle, which correlates with the severity of shock. This implies an early
      transition to anaerobic glycolysis during hemorrhagic shock, which may be
      indicative of early mitochondrial dysfunction.

PMID- 14676686
TI  - Pretreatment with high-fat enteral nutrition reduces endotoxin and tumor necrosis
      factor-alpha and preserves gut barrier function early after hemorrhagic shock.
AB  - Gram-negative sepsis is a potentially fatal clinical syndrome characterized by a
      proinflammatory response (tumor necrosis factor-alpha) to bacterial (endo)toxins
      and gut barrier function loss. Recently, we found that high-fat enteral nutrition
      protects against late bacterial translocation in a model of hemorrhagic shock in
      rats. However, the basis for this protection is unknown. We hypothesized that the
      observed protection is the result of an early inhibition of endotoxin and the
      subsequent inflammatory response resulting in a preserved gut barrier function.
      Sprague-Dawley rats were divided into a group that was starved overnight (HS-S),
      fed with a low-fat enteral diet (HS-LF) or fed wih a high-fat enteral diet (HS
      HF), and subsequently subjected to a nonlethal hemorrhagic shock. Ninety minutes
      after hemorrhage, arterial endotoxin significantly decreased in HS-HF rats (4.0
      +/- 0.6 pg/mL) compared with HS-LF rats (10.7 +/- 0.9 pg/mL, P = 0.002) and HS-S
      rats (15.2 +/- 2.2 pg/mL P = 0.001). Interestingly, arterial tumor necrosis
      factor-alpha was also decreased in HS-HF rats (17.9 +/- 10.4 pg/mL) compared with
      HS-LF (83.5 +/- 16.7 pg/mL, P < 0.01) and HS-S rats (180.9 +/- 67.9 pg/mL, P <
      0.02). Loss of tight junction structure (ZO-1) observed in ileum and colon of
      control hemorrhagic shock rats was prevented in HS-HF rats. In parallel,
      intestinal barrier function was preserved in HS-HF rats, evidenced by a reduced
      permeability to horseradish peroxidase (P < 0.05), less bacterial invasion, and a
      10-fold reduction of bacterial translocation early after hemorrhagic shock. This
      report describes a new strategy to nutritionally prevent endotoxemia, the
      subsequent inflammatory response and gut barrier failure following hemorrhagic
      shock. High-fat enteral nutrition requires further evaluation as an intervention
      to prevent a potentially fatal systemic inflammatory response in patients at risk
      for sepsis.

PMID- 14676687
TI  - Release of S100B differs during ischemia and reperfusion of the liver, the gut,
      and the kidney in rats.
AB  - S100B, an acknowledged marker of brain damage, is increased post-traumatically in
      plasma. The aim of this study was to investigate the diagnostic value of S100B
      release in experimental local extracranial ischemia and reperfusion. Anesthetized
      rats underwent laparotomy and ligation of the afferent blood vessels to the
      liver, gut, or kidney to achieve local ischemia in each organ separately. After
      60 min of ischemia, ligatures were removed and resuscitation was performed for 3
      h. S100B was determined in plasma by immunoluminometric assay 55, 65, and 240 min
      after the onset of ischemia (5 min before reperfusion and 5 min and 3 h after the
      onset of reperfusion). During ischemia of the liver, S100B increased before
      ligature removal and reperfusion, reaching significance early after the onset of
      reperfusion and remaining almost unchanged throughout reperfusion. In contrast,
      S100B did not increase during ischemia of the gut or kidney before ligature
      removal or during early reperfusion but increased significantly to similar levels
      as during reperfusion of the liver 240 min after the onset of ischemia (after 3 h
      of reperfusion). Our findings show for the first time that S100B increases during
      local extracranial ischemia and reperfusion. These experimental findings support
      the concept that brain damage is not necessarily the cause of increased S100B.
      Although S100B has been an acknowledged marker of brain damage for years, our
      experimental clinically relevant data indicate that S100B is, in fact, not
      specific as a marker of brain damage in the setting of local ischemia and
      reperfusion of the liver, gut, and kidney because local ischemia and reperfusion
      of these organs cause an S100B increase per se.

PMID- 14676688
TI  - In vivo and in vitro cytokine modulatory activity of newly synthesised 2
      aminotetraline derivatives.
AB  - In the present study, the protective effect of newly synthesised 2
      aminotetralines was investigated in murine models of toxic shock. A few
      derivatives protected mice against lethality induced by lipopolysaccharide from
      different bacterial strains and shock induced by staphylococcal enterotoxin B in
      mice sensitized by D-Galactosamine (D-Galn). Notably, one derivative, S(-)-2
      amino-6-fluoro-7-methoxy-1,2,3,4 tetrahydronaphthalene hydrochloride (ST1214),
      was also effective when administered orally (30 mg kg-1) in a therapeutic
      regimen. ST1214 markedly inhibited the production of the proinflammatory
      cytokines, such as tumor necrosis factor-alpha (TNF-alpha), Interleukin-1beta (IL
      1beta), Interleukin-12 (IL-12), interferon-gamma (IFN-gamma), as well as the
      inflammatory mediator nitric oxide (NO), and concurrently enhanced the production
      of the anti-inflammatory cytokine IL-10. Moreover, ST1214 dose-dependently
      reduced TNF-alpha production by human peripheral blood mononuclear cells and
      promonocytic THP-1 cells in vitro. In the latter, ST1214 was found to inhibit
      lipopolysaccharide-induced TNF-alpha secretion but not cytokine mRNA
      accumulation. These results suggest that the mechanism of action of ST1214
      involves blockade of posttranscriptional events of TNF-alpha production,
      apparently independent of p38 and ERK kinase activity. These results show
      beneficial effects of 2-aminotetralines in murine shock models and indicate a
      distinct counter-regulatory activity in down-regulating proinflammatory cytokine
      response, and upregulating IL-10. One derivative, i.e., ST1214, can be regarded
      as a lead compound in the development of novel drugs effective in anti
      inflammatory strategies.

PMID- 14676689
TI  - Evaluation of hyperdynamic resuscitation in 60% TBSA burn-injured sheep.
AB  - It has been suggested that hyperdynamic (HD) resuscitation improves outcomes. We
      hypothesized that initial HD resuscitation of burn injury using fluid and
      inotropes would improve metabolic function as indicated by base excess. We used
      an anesthetized ovine model of 60% TBSA full-thickness flame burn with delayed
      resuscitation started at 90 min after burn and continued for 8 h. Three groups (n
      = 6 each) were included: 1) HD defined as cardiac index (CI) of 1.5x baseline
      achieved by using Ringer's lactate alone (HD-Fluid); 2) Ringer's lactate and
      dobutamine (HD-Drug); and 3) Parkland Formula (Parkland) as a control group.
      Statistical analysis performed using analysis of variance and Tukey's HSD test.
      Significance accepted at P < 0.05. Higher CI was achieved in both HD-Fluid and HD
      Drug groups, e.g., at 8 h the CI was 4.6 +/- 0.4 and 4.7 +/- 0.6 L/min/m
      respectively, as compared with Parkland 3.6 +/- 0.5 L/min/m. The net fluid
      balance (fluid infused - urine output) was similar in both Parkland and HD-Drug
      groups, which were 2.5x more in HD-Fluid (P = 0.001). The mean postburn urinary
      outputs were similar in both Parkland and HD-Drug groups, e.g., Parkland (0.9 +/-
      0.08 mL/kg/h), HD-Drug (1.0 +/- 0.2 mL/kg/h) and increased in HD-Fluid (3.7 +/-
      1.0 mL/kg/h; P = 0.0005). Base excess remained positive in both HD-Drug (+2.5 +/-
      1 mmol/L) and Parkland (+1.5 +/- 1.7 mmol/L), and declined to -4.0 +/- 3.6 mmol/L
      in HD-Fluid group (P = 0.036). We conclude that there may be no benefit to using
      hyperdynamic regimens for the initial resuscitation of burn injury.

PMID- 14676690
TI  - The effect of different volumes of fluid resuscitation on traumatic-hemorrhagic
      shock at high altitude in the unacclimated rat.
AB  - The effects of different volumes of fluid resuscitation on traumatic hemorrhagic
      shock in unacclimated rats to high altitude were investigated. Seventy-eight
      Wistar rats were transported to LaSa, Tibet, 3760 meters above sea level, and
      traumatic hemorrhagic shock was induced by right-femur fracture plus bleeding to
      45 mmHg of mean arterial pressure (MAP) for 1 h under the anesthesia of sodium
      pentobarbital (40 mg/kg, i.p.). Experiments were conducted in two series. In
      series I, 36 rats were equally divided into six groups: sham-operated, untreated
      (traumatic shock without fluid infusion), and with lactated Ringer's
      resuscitation (LR) of 1.0, 1.5, 2.0 or 3.0 times the shed blood (1, 1.5, 2, 3 vol
      LR group). MAP, left intraventricular systolic pressure, the maximal change rate
      of intraventricular pressure rise or decline (+/-dp/dtmax), the maximal
      physiological velocity of contractile element shortening, and the area of left
      intraventricular pressure-dp/dt vector loop (Lo) were observed at 30, 60, 90, and
      120 min and the blood gases were determined at 30 and 120 min after
      resuscitation. Meanwhile the survival time was observed after the observation
      period. In series II, 42 rats were used to observe the effects of different
      volumes of fluid resuscitation on water content of lung and brain and hematocrit.
      One and 1.5 vol LR resuscitation significantly lifted MAP, left intraventricular
      systolic pressure, +dp/dtmax, and Lo, partially improved the blood gases and
      significantly prolonged the survival time. Although 2 and 3 vol of LR
      resuscitation caused apparent hemodilution and lung edema, they only partially
      improved hemodynamic parameters. Meanwhile 2 and 3 vol of LR resuscitation
      decreased the survival time. These results suggest that 1 and 1.5 vol of LR
      resuscitation can effectively resuscitate traumatic hemorrhagic shock at high
      altitude. More than two volumes of LR resuscitation would deteriorate the
      resuscitation outcome.

PMID- 14676691
TI  - Self-reported musculoskeletal symptoms among Danish women with cosmetic breast
      implants.
AB  - BACKGROUND: No epidemiological evidence of an association between silicone breast
      implants and connective tissue disease has been found. Based on case reports, it
      has been hypothesized that silicone breast implants may be associated with a
      unique rheumatic symptom cluster termed "atypical connective tissue disease."
      MATERIAL AND METHODS: We have evaluated self-reported rheumatic symptoms among
      women who received breast implants between 1977 and 1997 at 2 private plastic
      surgery clinics in Denmark. Women with other cosmetic surgery, including breast
      reduction, as well as women from the general population, were identified as
      controls. RESULTS: No statistically significant differences in mild (odds ratio
      [OR] = 0.9; 95% confidence interval [CI] = 0.6-1.3), moderate (OR = 0.7; 95% CI =
      0.4-1.2), or severe (OR = 1.1; 95% CI = 0.6-2.1) musculoskeletal symptoms were
      observed when women with breast implants were compared with women with other
      cosmetic surgery. Compared with women from the general population, women with
      breast implants were statistically significantly less likely to have mild or
      moderate musculoskeletal symptoms (OR = 0.5; 95% CI = 0.3-0.7 and OR = 0.3; 95%
      CI = 0.2-0.5, respectively); for severe symptoms the deficit was not
      statistically significant (OR = 0.7; 95% CI = 0.3-1.3). For individual symptom
      groups, there was no consistent pattern of reporting among women with implants.
      CONCLUSION: We did not find an excess of rheumatic symptoms or symptom clusters
      among women with breast implants. In fact, the occurrence of mild, moderate, and
      severe musculoskeletal symptoms was generally lower among women with implants
      compared with women with other cosmetic surgery and women in the general
      population.

PMID- 14676692
TI  - Superextended facelift: our experience with 3,580 patients.
AB  - Our experience using the "Superextended" facelifting technique in 3580 female
      patients is presented herein. The technique is based on extended subcutaneous
      facial and neck skin undermining, extensive superficial musculoaponeurotic system
      (SMAS) dissection with low lateral freeing of the edges of the platysma muscle.
      The trimmed SMAS is fixed to the adjacent tissues, enabling the upward and
      lateral pulling effect of the facial structures. The neck contour is rebuilt by
      lateral pulling and fixing of the dissected lateral platysmal edges, along the
      entire neck, and meticulous supraplatysmal fat sculpturing. The skin is redraped
      over the newly built SMAS and platysmal skeleton, trimmed, and sutured without
      any tension. The concept of beauty in the eyes of the surgeon is expressed by
      adding other ancillary procedures during or shortly after the main procedure.
      Subcutaneous forehead lift using the hairline incision was performed in 70% of
      the female patients, concomitantly with the face-lifting procedure. Upper and
      lower blepharoplasties, chin implant, perioral dermabrasion, rhinoplasty, and fat
      grafting have been performed according to the surgeon's judgment and the
      patient's request. The objectives of an ideal facial surgery, which are youthful,
      natural, dynamic, attractive, feminine, and long-lasting results, can be achieved
      using this technique. Lack of major complications and an overall minor
      complications rate of only 4.4% makes this technique safe, reproducible, and
      reliable. This is one of the largest presented series of this procedure,
      performed by 1 surgeon. The presented cases demonstrate the results obtained
      using this technique.

PMID- 14676693
TI  - Factors determining shape and symmetry in immediate breast reconstruction.
AB  - Although a number of studies compare different techniques of breast
      reconstruction there seems to be a paucity of information documenting the factors
      that affect breast shape and symmetry after immediate reconstruction. A
      photographic analysis by 5 plastic surgeons (who were blinded to the nature of
      the procedure) of 62 patients undergoing skin-sparing mastectomy and immediate
      reconstruction was undertaken in an endeavor to identify these factors.
      Autologous techniques used included deepithelialized pedicled transverse rectus
      abdominis musculocutaneous (TRAM) flaps (n = 23; in 9 patients a bilateral breast
      reduction using inverted-T keyhole skin markings was performed, and the TRAM flap
      was used to fill the reduced skin pocket) and 4 patients had extended latissimus
      dorsi flaps. Prosthetic reconstruction was undertaken in 35 patients in whom a
      bilateral breast reduction skin pattern was used in 23 (prosthesis inserted
      submuscularly in 5 patients and subcutaneously in 18 patients) or, in another 12
      patients the skin envelope was retained and the prosthesis was inserted partially
      submuscularly in 7 patients and subcutaneously in 5 patients. As a total group,
      the results of autologous reconstruction were better than prosthetic
      reconstruction (P = 0.048, Mann-Whitney U test). However, when a breast reduction
      pattern was used and the prosthesis was inserted subcutaneously, the results were
      not significantly better than when the reduced skin envelope was filled by
      autologous tissue (P = 0.64, Mann-Whitney U test). Failure to replace the areola
      leads to a smaller reconstructed breast and asymmetry. The skin envelope, when
      retained in toto, seems to be a major factor affecting breast shape. In patients
      with a reduction pattern applied, the skin envelope again seems to be a major
      factor affecting shape, because the results are similar whether the envelope was
      filled with autologous tissue or prosthetic material. The neoparenchyma is an
      important factor affecting breast projection. In patients undergoing prosthetic
      reconstruction, the results were significantly better with subglandular placement
      compared with submuscular placement (P = 0.007, Mann-Whitney U test). Patients
      who developed a complication (requiring debridement in the operating room or that
      took more than a month to achieve healing) had a poorer cosmetic result (P =
      0.015, Mann-Whitney U test). These factors need to be considered when planning
      breast reconstruction to optimize the aesthetic result.

PMID- 14676694
TI  - Pelvic reconstruction using vertical rectus abdominis musculocutaneous flaps.
AB  - Coverage of complex perineal wounds resulting from surgical and radiation therapy
      results in significant morbidity. Acute complications occur in 25% to 60% of
      patients. Serious complications occur in 25% to 46% of patients. Musculocutaneous
      or omental flaps are used as primary or salvage procedures for nonhealing
      perineal wounds. Vertical rectus abdominis flaps are ideally suited to bring
      nonirradiated tissue into defects associated with radical surgical extirpation
      procedures and irradiated fields.A retrospective review of 73 cases using a
      vertical rectus abdominis flap for perineal reconstruction is reported. Acute
      perineal wound complications occurred in 17.8%, while serious complications
      requiring reoperation occurred in only 3.5%. There was 1 complete flap failure.
      Primary healing occurred in 84.9% of patients, with 94.5% of patients obtaining a
      healed perineal wound within 30 days. These results support the use of the
      transpelvic vertical rectus flap in difficult perineal wound reconstruction.

PMID- 14676695
TI  - A comparison of 99 consecutive vaginal reconstructions: an outcome study.
AB  - This study compares the outcome of Singapore flap, vertical rectus abdominis
      musculocutaneous flap (VRAM), and gracilis musculocutaneous flap vaginal
      reconstruction. A retrospective review of 99 consecutive patients with complete
      vaginal defects was conducted at the Mayo Clinic from January 1988 to October
      2001. All possible complications were determined for each of the 3 reconstructive
      techniques, along with the effects of radiation and smoking on the respective
      complication rates. Preoperative and postoperative sexual function and adequacy
      were compared between each group. Ninety-nine patients ranging in age from 19 to
      80 years (mean, 51.6 years) were compared, with a mean follow-up of 28.9 months.
      Forty-one VRAM, 13 gracilis, and 45 modified Singapore flaps were used for
      vaginal reconstruction. The majority was due to acquired vaginal defects due to
      recurrent pelvic malignancy. The overall complication rate was lower following
      VRAM than either gracilis or Singapore flap reconstructions (13/41, 31.7%; 8/13,
      61.5%; and 21/45, 46.7%, respectively). The flap specific complication rate was
      least in the VRAM group (9/41, 22%; 7/13, 53.8%; and 17/45, 37.8%, respectively).
      The VRAM had a significant protective effect against the development of
      postoperative small bowel obstruction. Preoperative sexual activity predicted
      postoperative activity in 75 of 88 patients (85.2%) and was not affected by the
      type of reconstruction, although more patients with a Singapore flap required
      vaginal dilatation to maintain patency. In conclusion, the VRAM has a lower
      overall and flap-related complication rate compared with either gracilis or
      Singapore flap reconstruction. It has become our vaginal reconstructive flap of
      choice.

PMID- 14676696
TI  - Mandibular reconstruction: are two flaps better than one?
AB  - This study compared the combined iliac and ulnar forearm flaps with the
      osteomusculocutaneous fibular free flap for mandibular reconstruction. A
      retrospective study of 40 patients who had oromandibular reconstruction was
      performed, of whom 23 patients had a combined iliac crest without skin and ulnar
      forearm free flap. Seventeen patients had an osteomusculocutaneous free fibular
      flap. Ten women and 30 men with a mean age of 57.5 years comprised this study
      population. Ninety percent of the cases were squamous cell carcinoma (55%, T4),
      of which 11% were recurrent tumors. Anterolateral mandibular defects constituted
      52.9% of the fibular reconstructions and 60.9% accounted for the iliac/ulnar
      reconstructions. The mean bone gaps were 8.79 cm and 8.95 cm respectively.
      Functional evaluation was based on the University of Washington Questionnaire
      through phone calls and personal communication. The mean hospital stay was 15.43
      days and 10.09 days for the fibular and iliac/ulnar flaps respectively. The
      facial artery (64.7%) and facial vein (60%) were the main recipient vessels for
      the fibular reconstructions whereas the external carotid artery (95.6%) and the
      internal jugular vein (66.7%) were the main recipient vessels for the iliac/ulnar
      reconstruction. Overall flap survival was 96.8% (100% of fibular flaps and 95.65%
      of iliac/ulnar flaps). Two flaps were lost in the iliac/ulnar series because of
      unsalvageable venous thrombosis. Local complications for the iliac/ulnar flaps
      were 30.4% but were 5.9% for the fibular reconstructions. Function such as
      speech, swallowing, and chewing were notably better in the fibular than the
      iliac/ulnar group in 23 of the patients tested. The cosmetic acceptance of 77.8%
      of the fibular flaps was judged to be excellent and good, whereas 71.4% of the
      iliac/ulnar flaps were rated good. It appears that within this study population
      the free osteomusculocutaneous fibular flap had fewer local complications and a
      higher flap survival rate than the combined iliac/ulnar forearm flaps. Overall
      functional outcome was also improved. The use of the double flap may be
      appropriate in massive oromandibular defects, but may be less appropriate in more
      modest functional reconstructions of mandibular defects.

PMID- 14676697
TI  - Outcome for traumatic optic neuropathy--surgical versus nonsurgical treatment.
AB  - This study was performed to identify factors that can affect the final outcome
      and to recognize the proper management for patients with traumatic optic
      neuropathy (TON). This retrospective study included 42 consecutive patients with
      TON after maxillofacial trauma. Megadose methylprednisolone was administered to
      all patients during the first 3 days after diagnosis. Twenty-four patients
      received treatment with megadose steroids combined with optic nerve decompression
      and the remaining 18 with megadose methylprednisolone alone. Initial visual
      acuity (IVA) was the statistically significant factor affecting the outcome of
      TON (P = 0.006 for improvement rate). Patients treated within 7 days after injury
      had a better improvement degree, P = 0.056. Patients in a surgical group with an
      IVA of no light perception (NLP) had a better improvement rate and degree (31.3%;
      59.34 +/- 22.18%) than those in nonsurgical group (0%, 0%; P = 0.272). Initial
      visual acuity is the critical factor that affects the outcome of TON. Surgical
      optic nerve decompression is considerable in maxillofacial trauma patients with
      an IVA of NLP.

PMID- 14676698
TI  - Dorsal metacarpal island flap in syndactyly treatment.
AB  - Web space reconstruction is an important component of syndactyly treatment. There
      are several methods for a skin graft-free reconstruction. Previously, the dorsal
      metacarpal island flap based on a direct cutaneous branch of the dorsal
      metacarpal artery has been used as an island V-Y advancement for web defects in
      syndactyly. In this study, dorsal metacarpal artery flap was raised similarly as
      an island but was used instead as a transposition flap in a series of 19 web
      defects. Early results of a median (range) follow-up of 3 (1-5) years reveal
      neither recurrence of the deformity nor web creeping. Such utilization of the
      flap enables a better use of the skin territory proximal to the pedicle and a
      more comfortable reconstruction of the web space.

PMID- 14676699
TI  - Management of early groin vascular bypass graft infections with sartorius and
      rectus femoris flaps.
AB  - Groin infections adjacent to vascular bypass grafts continue to be a source of
      morbidity. The authors reviewed retrospectively 9 consecutive patients with early
      localized groin infections treated at their institution with sartorius or rectus
      femoris muscle flaps between 1998 and 2002. All wounds were initially opened and
      drained. Wounds with necrotic tissue were treated with serial surgical
      debridements, with a vacuum-assisted closure device, or with wet-to-dry dressing
      changes. Two bypass grafts were excised and replaced in the presence of marked
      exposure or pseudoaneurysm. Small wounds were closed with a turnover sartorius
      flap and larger wounds were closed with either a muscle or musculocutaneous
      rectus femoris flap. Groin wounds healed in all patients without subsequent graft
      exposure, rupture, or pseudoaneurysm. Local wound therapy with staged debridement
      and muscle flaps is effective for most early localized graft infections.

PMID- 14676700
TI  - Chest wall reconstruction using iliac bone allografts and muscle flaps.
AB  - Technically we can divide full-thickness thoracic reconstruction into 2 parts:
      providing a rigid support and ensuring well-vascularized coverage. Since 1986,
      the authors' center has had ample experience with bone banks and the use of
      cryopreserved bone grafts, which led them to consider the possibility of using
      these grafts for full-thickness chest wall reconstruction. They describe 3
      patients in whom resection of the tumor and reconstruction of the thorax were
      carried out using iliac bone allografts covered with muscle flaps (1 pectoralis
      major and 2 rectus abdominis). None of the patients experienced breathing
      difficulties, pain, or instability after 14 months, 18 months, and 11 years of
      follow-up. The result of the reconstruction was excellent in all 3 patients in
      terms of function and aesthetics. The advantage of allografts compared with
      synthetic materials is their potential integration; they can become part of the
      host patient's living tissue.

PMID- 14676701
TI  - Do multiple venous anastomoses reduce risk of thrombosis in free-flap transfer?
      Efficacy of dual anastomoses of separate venous systems.
AB  - Whether or not multiple venous anastomoses reduce the risk of free-flap failure
      is a subject of controversy. We report here, for the first time, on the
      importance of selecting 2 separate venous systems of the flap for dual
      anastomoses. The efficacy of multiple anastomoses was verified through a
      retrospective review of 310 cases of the free radial forearm flap transfer. Dual
      anastomoses of separate venous systems (the superficial and the deep) showed a
      lower incidence of venous insufficiency than single anastomosis did (0.7% versus
      7.5%; P < 0.05). On the other hand, dual anastomoses of a sole venous system
      showed no significant difference in the incidence of venous insufficiency
      compared with single anastomosis (11.5% versus 7.5%; P = 0.48). Our results
      suggest that dual venous anastomoses of separate venous systems is conducive to
      reduced risk of flap failure and affords protection against venous catastrophe
      through a self-compensating mechanism that obviates thrombosis of either
      anastomosis.

PMID- 14676702
TI  - Modification of insulin, glucose and cholesterol levels in nonobese women
      undergoing liposuction: is liposuction metabolically safe?
AB  - An open autocontrolled clinical study was performed on 15 healthy nonobese women
      who underwent liposuction to establish how metabolic profiles are modified in the
      short-term postsurgical period. Preoperative glucose, insulin, and cholesterol
      levels were determined. Also, impedancometry was used to determinate body
      composition. After 3 postoperative weeks, the levels and determinations were
      again tested. The results demonstrated a significant difference in glucose,
      cholesterol, insulin secretion, and adiposity, but insulin levels, glucose
      insulin relationship, and insulin sensitivity remained unaltered. From the
      results of this study, we consider liposuction to be a safe surgical procedure
      from a metabolic point of view because it improves the levels of cholesterol,
      glucose, and insulin secretion and at the same time decreases adiposity.
      Therefore, in the short term, liposuction can modify important markers for the
      development of type II diabetes mellitus and cardiovascular disease.

PMID- 14676703
TI  - Conjunctivorhinostomy with rubber-tipped Jones tube.
AB  - One of the problems of conjunctivorhinostomy that employs the conventional Jones
      tube is that the end of Jones tube has to be manipulated by the surgeon so that
      the tube resides within the nasal cavity while not touching the middle turbinate
      and the nasal septum. As a result, patients who have high nasal septal deviation,
      paradoxical curvature, or middle turbinate hypertrophy have inadequate space in
      the nasal cavity for the Jones tube to rest. Such patients required either
      septoplasty or turbinectomy prior to conjunctivorhinostomy. To overcome such a
      problem, the authors connected a 4 French rubber tube to the tip of the Jones
      tube and helped the end of the tube to reside within the nasal cavity regardless
      of the anatomic variation of nasal septum or the middle turbinate. When such
      modified procedure is used, the Jones tube makes good contact with the
      conjunctiva, lacrimal sac, and the nasal mucosa while the rubber tube remains
      afloat within the nasal conjunctiva. Such modification helps the tube to reside
      within the nasal cavity without foreign body reactions and granulation tissue
      complications, and there is no need to change tubes to make up for the loss of
      tube length because of postoperative tissue contracture. Between April 2000 and
      August 2001, the authors performed conjunctivorhinostomy with a rubber-tipped
      Jones tube on 8 patients with drainage problems of the nasolacrimal duct system
      and obtained satisfactory results without complications.

PMID- 14676704
TI  - The single-fascicle method of nerve grafting.
AB  - In this study a single-fascicle technique for neural deficits repair was
      evaluated using a rat sciatic nerve model. Twenty-four Lewis rats were divided
      into 4 groups: group 1, 1.5-cm deficit without repair; group 2, conventional
      autograft; group 3, large-fascicle autograft; and group 4, small-fascicle
      autograft. Nerve regeneration was evaluated by pin-prick and toe-spread tests.
      Nerve samples were estimated by histomorphometry. Group 1 presented no recovery.
      Groups 3 and 4 demonstrated significantly better pin-prick results compared with
      those from conventional repair. Histology revealed a significantly higher number
      of axons and myelin thickness in the small-fascicle (2.8 +/- 0.4 x 10(3) axons,
      4.22 +/- 0.41 microm) and large-fascicle (5.1 +/- 1.7 x 10(3) axons, 4.62 +/-
      0.28 microm) groups compared with the conventional autograft group (2.1 +/- 0.3 x
      10(3) axons, 2.93 +/- 0.20 microm). The small-fascicle group had a significantly
      greater mean axon area (58.59 +/- 15.81 microm2) than the large-fascicle group
      (29.66 +/- 12.67 microm2) and the conventional group (25.35 +/- 7.52 microm2). In
      this study, peripheral nerve repair using a single-fascicle graft resulted in
      faster functional recovery and better morphometric outcome compared with
      conventional nerve repair.

PMID- 14676705
TI  - Effects of granulocyte macrophage colony stimulating factor on random flap
      healing and immune profile in rats with impaired wound healing by
      glucocorticoids.
AB  - Wound healing involves inflammation, cell proliferation, matrix deposition, and
      tissue remodeling. Priming the tissue to be incised with proinflammatory
      cytokines offers a new approach to wound healing. This has been studied mostly in
      incisional wounds till now. This study was designed to investigate the role of
      granulocyte macrophage colony stimulating factor (GM-CSF) priming of planned
      incision lines in random flaps in rats with impaired wound healing due to
      glucocorticoid administration, and immune profiles of rats were also evaluated.
      GM-CSF priming of incision lines in immunosuppressed rats was shown to improve
      the wound healing parameters, hydroxyproline levels, breaking strength, flap
      survival, and immune profile, although all of the parameters were somewhat lower
      than those of control group. The findings of this study suggest that wound
      healing can be accelerated and thus morbidity lowered by making use of the
      immunomodulator effects of GM-CSF in cases where wound healing is impaired due to
      systemic disease or drug use and flap reconstruction is necessary.

PMID- 14676706
TI  - Restoration of quadriceps femoris function with a dynamic microsurgical free
      latissimus dorsi muscle transfer.
AB  - Loss of knee extension caused by quadriceps femoris muscle disruption can be a
      disabling injury. Attempts at reconstructing the large muscle deficit after
      oncological resections of the quadriceps have previously had some success using a
      dynamic free latissimus dorsi muscle transfer. This concept proved to be
      similarly valuable after a gunshot wound to the thigh resulted in an isolated
      loss of the quadriceps mechanism. A reinnervated latissimus dorsi muscle bridging
      the quadriceps muscle gap proved to have active contraction and permitted full
      active knee extension, demonstrating the value of this muscle also for
      restoration of function after traumatic injuries.

PMID- 14676707
TI  - Turnover TRAM flap as a diaphragmatic patch.
AB  - A hole in the diaphragm requiring an exogenous material for repair is exceedingly
      unusual. Unfortunately, many nearby potential flap options for this role have
      frequently already been violated by prior thoracotomies. The ipsilateral superior
      pedicled lower transverse rectus abdominis musculocutaneous (TRAM) flap could
      then be an important maneuver for salvage. Via a tunnel leading into the chest
      cavity, a deepithelialized TRAM flap can readily reach basilar thoracic defects,
      and[U0292] thus is particularly suited as an autogenous patch for the diaphragm.

PMID- 14676708
TI  - Y-shape hard palate mucoperiosteal graft and V-Y advancement flap in the
      reconstruction of a combined defect involving lateral canthus and upper and lower
      eyelids.
AB  - Curative ablation of a baso-squamous cell carcinoma of lateral cantus and both
      eyelids resulted in a complex full-thickness defect of upper and lower eyelids,
      lateral canthal area, and lateral canthal tendon. The reconstruction of the
      defect was performed in a single stage using a Y-shape hard palate mucoperiosteal
      graft and a Y-shape skin flap advanced from the temporal side of the defect on
      its subcutaneous pedicle. The graft donor site healed spontaneously and the flap
      donor site was closed primarily. A durable and stable coverage of the defect
      could be achieved with minimal donor site morbidity.

PMID- 14676709
TI  - Reconstruction of traumatic Stensen duct defect using a vein graft as a conduit:
      two case reports.
AB  - Treatment of Stensen duct defect is still controversial. The authors describe the
      successful use of a retrograde vein graft as a conduit for traumatic segmental
      Stensen duct defect reconstruction. One patient sustained facial trauma with
      severe duct crushing and severance, the other had multiple cutting injuries with
      segmental duct defect. However, primary repair was impossible. A retrograde vein
      graft harvested from forearm for Stensen duct defect reconstruction was performed
      using microsurgical technique. A silicon stent was retained for 8 weeks. The
      sialographic examination showed good functional results without stricture
      postoperatively. This could be an option for treating such a complicated defect.

PMID- 14676710
TI  - An alternative approach for correction of Stahl's ear.
AB  - A technique of correction of Stahl's ear is presented and is compared with other
      techniques reported in the literature.

PMID- 14676711
TI  - The gender genie.

PMID- 14676712
TI  - On the use of Lactosorb plate for fixation of a metacarpal shaft fracture.

PMID- 14676713
TI  - Re: Reconsidering the soleus muscle flap for coverage of wounds of the distal
      third of the leg.

PMID- 14676715
TI  - Has the HIV/AIDS epidemic changed sexual behaviour of high risk groups in Uganda?
AB  - BACKGROUND: Uganda, was the first country in sub-Saharan Africa to reverse its
      HIV/AIDS epidemic. Long distance drivers, prostitutes and barmaids have been
      identified as the groups that engage in risky sex, which promotes HIV
      transmission in Uganda and other countries across the continent. This paper
      investigates whether and why there were changes of sexual behaviour and practices
      among five risky groups in Uganda as a consequence of HIV/AIDS epidemic.
      METHODOLOGY: The paper is based on data generated from a survey on 'resistance to
      sexual behaviour change in the African AIDS epidemic', which was conducted in the
      districts of Kabale, Kampala and Lira in 1999. For purposes of this paper, only
      data from the focus group discussions with high-risk groups have been analysed.
      These include commercial sex workers, street children, long haul truck drivers,
      bar maids and adolescents in three towns of Uganda (Kabale, Kampala, Lira).
      RESULTS: Results indicate that despite the HIV/AIDS epidemic, these groups had
      only changed their sexual behaviour a little, and they reported to be continuing
      with multiple sexual partners for a variety of reasons. The adolescents and
      street children were under peer pressure and a lot of sexual urge; commercial sex
      workers and bar maids attributed their risky behaviour to the need to survive due
      to the existing poverty; and the truck drivers reflected on the need for female
      company to reduce their stress while on the long lonely travels across Africa.
      Nevertheless, they are all aware and perceive people with multiple sexual
      partners as being highly vulnerable to contracting HIV and they all reported to
      have adopted condom use as an HIV preventive strategy. They also observed that
      married people were at a high risk of contracting HIV due to non-use of condoms
      in marital relationships and unfaithfulness of spouses. CONCLUSIONS Females
      engage in high-risk sexual relations as a means of economic survival, and
      perceive their acts as a strategy to improve their socio-economic well being. On
      the contrary, men in these high-risk categories do such acts out of pleasure and
      as avenues for attaining fulfilled sexual lives. The search for money among women
      and the constant desire for men to have sexual pleasure, which are greatly
      facilitated by their financial status are the forces behind reckless sexual
      behaviour among high-risk groups.

PMID- 14676716
TI  - Sexual practices of women within six months of childbirth in Mulago hospital,
      Uganda.
AB  - OBJECTIVES: To establish the sexual practices and their associated morbidity
      among women within 6 months of childbirth in Kampala Uganda. DESIGN: Cross
      sectional descriptive study. SETTING: The three Mulago hospital child
      immunization clinics. PARTICIPANTS: Two hundred and seventeen eligible mothers
      took part in the study from November to December 2001. OUTCOME MEASURES: Time to
      resumption of sexual intercourse after childbirth, reasons for resumption and
      problems associated with it. METHODS: Partially coded questionnaires RESULTS:
      Sexual intercourse was resumed by 66.4% of the women within six months of
      childbirth. Of these 49.3% did so during the puerperium. The main reasons for
      early resumption of sexual intercourse were husbands' demands, cultural demands
      and inherent inability to do without sexual intercourse but not level of
      education of mothers. Of the mothers who resumed sexual intercourse 22.2% had
      sexual problems. The problems included vaginal pain (62.5%), discharge (18.8%),
      bleeding (15.6%) and bruises or tears (3.1%). Perineal or genital damage at the
      time of delivery was not associated with a delayed resumption of sexual
      intercourse with (OR1.08, 95% CI 0.51-2.30). Of those who had sexual intercourse
      and had problems only 59.4% sought medical assistance. The reasons for not
      resuming sexual intercourse within six months of delivery included advise from
      health workers (38.4%), husbands were away (21.9%), no interest (21.9%) and not
      feeling well(17.8%). CONCLUSION: Most women resumed sexual intercourse within six
      months of childbirth and had high morbidity. There is need for appropriate
      postpartum sexual practice advice. SITE OF STUDY: Mulago hospital.

PMID- 14676717
TI  - Acute toxicity effects of the methanolic extract of Fagara zanthoxyloides (Lam.)
      root-bark.
AB  - BACKGROUND: Fagara zanthoxyloides is a well known medicinal plant in Uganda. It
      is used extensively in malaria and other infections. However nothing is known
      about its toxicity. OBJECTIVE: The objective of the study was to evaluate the
      acute toxicity of the methanolic extract of the root-bark of F. zanthoxyloides,
      in mice. METHODS: Methanolic extract of the root-bark of the plant was
      administered orally to mice at various dose levels to determine the acute toxic
      effects and the median lethal dose (LD50) in mice. RESULTS: The LD50 of the
      methanolic extract was found to be 5.0 g/Kg body weight within 95% confidence
      limits. The mice showed signs of cerebral irritation before dying.
      Histopathological examinations of the viscera showed congestion and focal
      necrosis of the liver and renal tubules. CONCLUSION: It was concluded that the
      extract of F. zanthoxyloides is safe, however the cerebral mechanism that lead to
      the death of the mice need to be investigated further.

PMID- 14676718
TI  - Adequacy and efficiency of nursing staff in a child-welfare-clinic at Umtata
      General Hospital, South Africa.
AB  - BACKGROUND: South Africa has a serious shortage of human and financial resources
      to provide primary healthcare services especially in the historically under
      served areas. It is a tedious task to carry out healthcare delivery for the
      masses without rationalizing human resources in the form of re-allocation and re
      deployment of healthcare personnel. This study aimed to establish the level of
      adequacy and efficiency of nursing staff in the former Transkei region. The study
      was carried out in the child and family welfare clinic of the Umtata General
      Hospital. OBJECTIVE: To assess adequacy and efficiency of nursing staff in a
      child welfare clinic. METHOD: This was a retrospective study. The workload of two
      nurses allocated to the child welfare clinic at Umtata General Hospital South
      Africa was calculated based on the patient numbers and hours of work per week.
      Calculations excluded time breaks for tea, lunch and annual leave. This work load
      was compared to the norms of standard examination time that is 12 minutes per
      patient obtained from the sub directorate of Natalia Office of the Department of
      Health. Information regarding number of patients attended to by the nurses and
      their disease conditions was obtained from retrospective review of hospital
      records. RESULTS: While each nurse was on duty for 8 hours per day each had only
      6 reproductive hours. The two nurses examined only 310 patients giving staff
      utilization of 2.46% (i.e. 310/12600) and adequacy of staff of 0.0492 or
      310/6300. CONCLUSION: There is under-utilization of the staff in Umtata General
      Hospital, South Africa. RECOMMENDATION: To increase utilization of the nurses a
      process of sharing and merging with a clinic or a ward with similar type of work
      is recommended.

PMID- 14676719
TI  - Imaging features of brain tuberculoma in Tanzania: case report and literature
      review.
AB  - Brain tuberculomas are a rare manifestation of mycobacterium tuberculosis
      infection usually resulting from hematogenous spread of the bacteria from a
      primary focus elsewhere in the body. A 29-year-old female with no history of
      pulmonary tuberculosis or signs of pulmonary infection presented with signs and
      symptoms of raised intracranial pressure. She underwent CT and MR imaging where
      multiple enhancing lesions were revealed in the brain parenchyma. The features of
      tuberculoma on CT and MR imaging may mimic the appearance of several other brain
      lesions. Histological diagnosis of tuberculoma was obtained. In areas where
      tuberculosis is endemic, the imaging features of brain tuberculoma have to be
      readily recognized by attending doctors.

PMID- 14676720
TI  - Nutritional update: relevance to maternal and child health in East Africa.
AB  - In this review of recent advances in nutrition, we shall follow the 'life cycle'
      with special attention to maternal and foetal nutrition, linear growth, and
      nutritional assessment. We also consider nutrition, infection and micronutrients,
      and recent concepts of the pathophysiology and management of protein energy
      malnutrition PEM.

PMID- 14676721
TI  - Rectal exam mistaken for sodomy, a patients personal experience!

PMID- 14676722
TI  - Phenomenology: learning from our patients and ourselves.

PMID- 14676723
TI  - An introduction to the Micrel Micropump MP Daily portable syringe driver.
AB  - In this article the author describes the Micrel Micropump MP Daily (MP Daily)
      portable syringe driver. This follows the author's experience of a 4-month pilot
      of the device by an inpatient palliative care unit. Portable syringe drivers are
      commonly used to deliver continuous subcutaneous infusions in palliative care
      situations. Those in current use are not without problems and serious adverse
      events have occasionally been reported, mainly resulting from confusion between
      models. The MP Daily syringe driver addresses some of these issues while
      remaining small, lightweight and inexpensive, with a long battery life and
      fitting into the pocket of a shirt of pyjama jacket. Improvements over current
      models include an on/off button, the absence of facilities to set a zero rate or
      change the rate once the syringe driver is running, and the absence of a boost
      button. In addition, there are improved alarms, a message display system and a
      configuration menu. Although confusion remains a problem, and the ideal has not
      yet been reached, the MP Daily goes some considerable way towards reducing risks
      and opportunities for human error.

PMID- 14676724
TI  - Pressure ulcers in palliative care: development of a hospice pressure ulcer risk
      assessment scale.
AB  - The aim of this study was to construct a pressure ulcer risk assessment scale
      appropriate for palliative care patients. Risk assessments were performed using
      the modified Norton scale and nine newly constructed scales, consisting of the
      modified Norton scale with various changes. Data were collected from 98 patients
      in a Swedish hospice between April 1999 and September 2000. Pressure ulcer
      occurrence was registered weekly in the patient record. Increasing age, male
      gender, physical inactivity, immobility, decreasing food and fluid intake,
      incontinence, poor general physical condition and lean body constitution were
      shown to be significant risk factors for development of pressure ulcers in
      terminally ill cancer patients. After further testing of the data, one scale was
      found to be superior in identifying patients at risk, with higher validity than
      the modified Norton scale. The assessment items in this new scale, The Hospice
      Pressure Ulcer Risk Assessment Scale (in Swedish: Hospice Riskbedoming Trycksar,
      (HoRT)), are physical activity, mobility and age.

PMID- 14676725
TI  - Is there a need for an interactive teaching tool on pain management in cancer?

PMID- 14676726
TI  - Telemedicine in community-based palliative care: evaluation of a videolink
      teleconference project.
AB  - A national shortage of consultants in palliative medicine in the UK has led St
      David's Foundation Hospice Care to begin an innovative telemedicine project. This
      enabled the foundation's clinical nurse specialists (CNSs) in palliative care to
      access consultant advice and support. Each week the CNSs held a 2-hour
      teleconference session with a consultant in palliative medicine by video link to
      discuss patients with one or more unresolved symptoms or significant palliative
      care issues. The use of teleconference time was structured and targeted, which
      allowed the limited time available to be used productively. After each session,
      the participants completed a number of questionnaires which were used, with data
      collected during focus-group sessions, to analyse the project. Despite the
      relatively new and complex technology, the nurses involved were very comfortable
      using the teleconferencing equipment. All the nurses involved rated the advice
      given during the teleconferences as helpful or very helpful. The project has
      shown that telemedicine can provide a useful, and probably cost- and time
      effective, addition to current services.

PMID- 14676727
TI  - Palliative care for Sikhs.
AB  - This article provides an overview of the palliative care needs of Sikh patients.
      It describes the basis of Sikh beliefs and practices and discusses practical
      aspects of caring for terminally ill Sikh patients and their families. Issues
      before and after death are considered and the importance of an individual
      approach is highlighted.

PMID- 14676728
TI  - Diagnostic approach and therapy of overgrowth and tall stature in childhood.
AB  - Although referral for evaluation of tall stature is much less common than for
      short stature, early diagnosis in the paediatric age of clinical pictures leading
      to tall stature is crucial, both in order to detect conditions which can be
      properly treated and in order to limit excessive final heights; nowadays tall
      stature may be cause of psychosocial problems. This paper reviews different items
      related to tall stature in childhood. First of all, our review focuses on the
      definition of tall stature and the classification of the main clinical conditions
      associated with either tallness or excessive growth is discussed. Secondly, the
      clinical picture and the most recent breakthroughs of each of these conditions
      are reviewed. A diagnostic flow-chart meant to approach a patient presenting with
      tall stature is designed according to a few simple parameters such as
      chronological age, height age, bone age and growth velocity. The novel advances
      in the understanding of constitutional and secondary tall stature are presented
      and discussed, together with the hormonal treatment of constitutional tall
      stature and other related outstanding questions.

PMID- 14676729
TI  - [Prolonged ICP monitoring in children with sylvian fissure arachnoid cysts].
AB  - BACKGROUND: The decision making process for patients with sylvian fissure
      arachnoid cysts still represents a challenge for the neurosurgeon. A high
      proportion of the patients is indeed asymptomatic, in spite of neuroimaging signs
      of apparently increased intracranial pressure (ICP). The aim of the present study
      was to evaluate the usefulness of prolonged ICP recording in the preoperative
      work-out. METHODS: Twelve children (11 M/1 F) harboring temporal arachnoid cysts
      were investigated (men age 6.3 years). According to Galassi classification they
      were subdivided into 3 groups. Group I included 3 patients with Type I cysts;
      group II comprised 6 children with Type II cysts; group III consisted of 3
      children with Type III cysts. An extensible silicone microprocessor (Codman ),
      developed for continuous ICP recording, was implanted intraparenchymally,
      adjacent to the major extension of the cyst. The collected information was cable
      unloaded to a PC and stored. All the patients underwent a minimum of 48 hours to
      a maximum of 72 hours ICP continuous check. Ten mmHg was arbitrarily chosen as
      the upper normal limit of ICP in resting conditions and the patients were
      classified according to the percentile distribution of their ICP daily and
      nightly pressure values. RESULTS: ICP recordings were in the normal range in all
      the 3 children with Type I cysts (49-86% <10 mmHg during the entire recording),
      in spite of the fact that 2 of them were apparently symptomatic. Three of the 6
      children with a Type II temporal cyst had elevated ICP values (69-99% >10 mmHG),
      even though they had an incidental (1 case) or prenatal (2 cases) diagnosis. The
      remaining 3 patients had normal ICP values for more than 70% of the recording
      time period. Two of the 3 patients with type III temporal arachnoid cysts had
      almost constantly abnormal ICP values (95=99% >10 mmHg); conversely the third
      patient showed normal ICP values for more than 80% of the recording time period.
      Five patients were operated on; in 4 of them the surgical indication was based on
      ICP recordings (2 of the 3 children with a Type II cyst and increased ICP and the
      2 patients with a Type III cyst and increased ICP). The last child, harboring a
      Type I cyst, was operated on under parents request, as a preventive measure. At a
      mean follow-up of 10.1 months all the patients operated on are in excellent
      clinical conditions; 1 of them (Type II cyst) initially submitted to craniotomy
      and cystic membrane excision needed a subdural-peritoneal shunt implant 3 months
      after surgery for the appearance of a symptomatic subdural hygroma on the side of
      the cyst. Postoperative CT showed signs of brain expansion in the 2 patients
      operated on for a Type III cyst, and in the patients operated on for a Type I
      cyst. CONCLUSIONS: With the limit of the relatively small series here presented,
      prolonged ICP recording appeared to be an important preoperative tool to rule out
      the necessity of operating on children with Type I cysts. Furthermore, it was
      particularly useful in the decision-making process for children with Type III
      cysts. In cases of Type II lesions, the investigation resulted less
      discriminating, though the ICP monitoring contributed to find out those patients
      in whom surgery was indicated in spite of the absence of symptoms.

PMID- 14676730
TI  - [Calcium-phosphate metabolism and bone markers in two patients with Noonan's
      syndrome treated with growth hormone].
AB  - AIM: To evaluate the possible effects of recombinant growth hormone (rhGH)
      therapy on mineral homeostasis and bone turnover, the authors studied calcium
      phosphate metabolism parameters, including some bone markers, in 2 prepubertal
      subjects with Noonan's syndrome (NS). METHODS: Two prepubertal males suffering
      from NS, short stature (-3.9 and -5.4 SDS respectively) and low growth velocity
      (3.9 and 3.3 cm/year), were treated with rhGH (0.85 U/kg/week) for 1 year. Serum
      levels of total calcium (Ca), inorganic phosphate (P), magnesium (Mg),
      parathyroid hormone (PTH), calcitonin (CT), 25OH vitamin D, 1.25(OH)(2)D,
      osteocalcin (BGP), type I procollagen carboxy-terminal propeptide (PICP) and its
      telopeptide (ICTP) were measured. RESULTS: The baseline values were in the normal
      range; during the treatment no remarkable difference in the values of every one
      parameters was detected in the 2 patients studied. In one of them, who responded
      to GH treatment with significantly improved growth velocity, serum levels of the
      BGP increased during the first semester, and then progressively declined;
      conversely, serum levels of the ICTP remained stable during the first 6 months of
      GH-therapy, whereas increased in the following 6 months. CONCLUSION: The results
      suggest that in Noonan's syndrome patients responding to GH-therapy, a
      stimulation of bone turnover, with ensuing increase of height velocity, takes
      place, at least during the first year of GH-therapy. The authors underline the
      necessity of confirming their results on a larger group of patients with Noonan's
      syndrome.

PMID- 14676731
TI  - Sub-inguinal interruption of dilated veins in adolescent varicocele: should it be
      considered a gold standard technique?
AB  - AIM: Surgeons of varicocele are at present still searching for a gold standard
      technique, which can correct varicocele without any recurrences, maintaining
      optimal testicular function, having got minimal current and future morbidity and
      being cost effective. We evaluated the presence of these criteria in the
      technique of sub-inguinal dilated vein interruption. METHODS: Between 1994 and
      2001, 142 youngsters and adolescents underwent surgery for varicocele repair at
      our hospital. Average patient age was 12.4 years (range 8 to 15). One-hundred-six
      cases (74.7%) were grade III varicocele, while 36 (25.5 ) were grade II. Grade II
      varicoceles underwent surgery only if associated with scrotal discomfort,
      testicular softness or hypotrophy of the affected testis (differential volume
      between the 2 testicles more than 20% or more than 2 ml ). Varicoceles were
      repaired using a subinguinal ligation of intrafunicular and extrafunicolar
      dilated veins. The testicular vaginalis was not touched in 46 children (Group A)
      but it was reversed in 42 and resected in the other 54 cases to prevent
      postoperative hydrocele. RESULTS: In 126 cases (88.7%) varicocele disappeared
      after surgery, in 12 (8.4%) a mild residual vein dilatation persisted but without
      any sign of reflux at color-Doppler ultrasound, in 4 patients a postoperative
      venous reflux was found. Thus, our recurrence rate is nowadays 2.8%. Average
      postoperative follow-up was 2.3 years (range 1 to 5 years). No testicular atrophy
      was observed. Based on our last series, at 1 year follow-up control (26 cases
      throughout year 2000), mean testicular volume, assessed by ultrasound, increased
      not significantly after surgery from ml 4.69 (SD+/-1.46) preoperative volume to
      ml 5.19 (SD+/-1.36) postoperative (p=0.2). CONCLUSION: First of all, we found a
      recurrence rate of 2.9% similar to the lowest of the other procedures. Regarding
      morbidity, the main inconvenience consists in postoperative hydrocele. It
      occurred in 13% of our 1st series (group A), but only in 4.1% of patients after
      reversion or resection of the vaginalis tunica. Average postoperative testicular
      volume increases after varicocelectomy in our patients, even if not
      significantly. About sparing the testicular artery or not it has been
      demonstrated that ligation of this artery doesn't impair testicular growth up and
      our own observations confirm this evidence. Thus we believe it to be more useful
      and safe to interrupt this artery to avoid recurrences due to a periarterial
      venous network. Finally we can conclude that sub-inguinal ligature of dilated
      veins, when approached with rigorous understanding of the pathophysiology of
      varicocele is a very safe procedure and low cost effectiveness.

PMID- 14676732
TI  - [Role of the endoscopic treatment of vesicoureteal reflux. A 16-years'
      experience].
AB  - AIM: Vesico-ureteral reflux (VUR) is the most common urological malformation in
      pediatric age; nevertheless its optimal management remains controversial. Until
      early 80s, treatment guidelines for VUR recommended the use of antibiotic
      prophylaxis as initial therapy, with surgical repair for patients with persistent
      VUR. Endoscopic treatment of VUR has gained popularity and has proved successful
      in a high percentage of cases, but its role in the clinical practice remains to
      be established. METHODS: In this paper, our series of 1029 patients and 1478
      refluxing ureters, treated from January 1986 to June 2001, is presented. Reflux
      ranged from grade II to grade IV. In the first 14 cases Teflon was injected.
      After 1989 bovine collagen was used in 442 children and, since 1996, Deflux, a
      nonallergenic, biodegradable dextranomer, in 573 cases. All patients were
      clinically evaluated for possible voiding dysfunctions. All patients completed a
      12 month follow-up period. RESULTS: After 1 or 2 injections, a voiding cystogram
      showed no VUR (or grade I) in 1123 ureters (76%). In grade II, III and IV success
      rates were, respectively, 87%, 73% and 48%. Complications were minimal (0.5%).
      CONCLUSION: These results confirm that endoscopic treatment of VUR is a valid
      alternative to "open surgery" and to antibiotic prophylaxis. Failure of treatment
      is usually due to dislocation of the implanted material, secondary to voiding
      dysfunction. In conclusion, we recommend the endoscopic treatment in the majority
      of VUR, for the short hospital stay, the absence of significant complications and
      the high success rate. In grade IV VUR, the use of endoscopic treatment is still
      questionable. Patients with voiding dysfunction should be identified and treated
      with appropriate therapy prior to attempt an endoscopic treatment of VUR.

PMID- 14676733
TI  - [Early-onset of primary intestinal lymphangiectasia. A case report and diet
      treatment].
AB  - Primary intestinal lymphangiectasia is a rare disorder, characterized by
      hypoproteinemia due to obstruction of the intestinal lymphatic vessels and loss
      of lymph fluid in the gastrointestinal tract. The case of a 3-month old patient
      with protein-losing enteropathy due to a primitive intestinal lymphangiectasia
      diagnosed with duodenal histology is reported. The adapted formula was replaced
      by a formula enriched with medium-chain triglycerides (MCT) and the patient
      presented a clinical and biochemical improvement. The importance of an early
      diagnosis and the efficacy of treatment with MCT is stressed.

PMID- 14676734
TI  - [Erythema nodosum induced by kerion celsi in a child with hypomelanosis of Ito].
AB  - A 3-year-old boy presented with an 8 week history of inflammatory nodular lesions
      on the scalp. Shortly afterwards painful subcutaneous nodules developed on the
      lower legs. Epidermophyton floccosum was isolated from the scalp lesions and a
      diagnosis of erythema nodosum induced by kerion celsi of the scalp was made. The
      patient was started on oral therapy with 250 mg/day griseolfuvin, associated with
      topical eosine and myconazol. Erythema nodosum represents a reaction pattern to a
      wide variety of inflammatory stimuli. The interest of this case lies in the
      unusual association of kerion celsi and erythema nodosum and in the
      identification of Epidermophyton floccosum in the lesions of the scalp.

PMID- 14676735
TI  - Transient fetal myelosuppressive effect of D-penicillamine when used in
      pregnancy.
AB  - Normal fertility is sustained by progress in the medical therapy of Wilson's
      disease; however, pregnancy complications are encountered more frequently. The
      mother we present is a Wilson's disease patient who had been compliant with D
      penicillamine for the preceding 13 years. She was admitted with unplanned
      pregnancy at the 16th gestational week. The dose of D-penicillamine could be
      reduced to 600 mg/d related to the underlying disease. Pregnancy ended with
      premature labor and delivery at the 29-30th weeks. The baby experienced type I
      respiratory distress and was treated by surfactant and mechanical ventilation.
      Neutropenia and leucopenia were documented at 6th postnatal hours. The baby
      showed neutropenia and leucopenia for 5 days and resolving without any further
      therapy. Intrauterine D-penicillamine was suspected to cause transient neonatal
      myelosuppression.

PMID- 14676736
TI  - [Induction of labour: which method to use?].
AB  - Induction of labour is a common obstetric instrument to employ when the potential
      risk to continue a pregnancy is higher than to terminate it. The methods of
      induction can be pharmacological or mechanical; the choice of the method mainly
      depends by the cervical ripening, as it is significantly able to influence,
      according to the type of induction, its final issue. The mechanical methods are:
      stripping and sweeping of the membranes, hand dilatation of cervix, intrauterine
      pressure catheters, Laminaria Japonicum, transcervical Foley catheter and
      amniotomy. To pharmacological methods include some agents such as the
      prostaglandins (PG), the most common approach to induce a labour, and used above
      all by vaginal way in patients with unripe cervix. They simulate the natural PG
      effects at the beginning of delivery and show a great efficiency. There are a lot
      of PG on the market, but except some of them, as Dinoprostone for PGE2 and
      Misoprostol for PGE1, no one of them shows the same safety in management of
      labour. Oxytocin, another inductive method, administered by diluted intravenous
      infusion, is utilized alone or mainly with other methods when the labour is
      started or with rupture of the membranes, because it begins or maintains the
      myometrial contraction.

PMID- 14676737
TI  - Utilisation of hydrogen peroxide in the treatment of recurrent bacterial
      vaginosis.
AB  - AIM: The authors have evaluated the real efficacy of using hydrogen peroxide for
      previously treated recurrent bacterial vaginosis that is resistant to other forms
      of treatment. METHODS: The study included 58 women aged between 18 and 42 years
      old. Vaginal irrigations with 30 ml of hydrogen peroxide (3%) were prescribed in
      the evening for a week. The follow-up was carried out 3 months after the end of
      treatment. RESULTS: The results clearly show that the use of hydrogen peroxide in
      vagina can eliminate the main symptoms of bacterial vaginosis, and in particular
      the malodorous leucoxanthorrhea in 89% of cases at 3 months after the end of
      treatment, a result that is comparable to that obtained using metronidazole or
      clindamycin as a vaginal cream. Moreover, hydrogen peroxide facilitates the
      restoration of normal vaginal bacterial flora (represented by H202-producing
      lactobacillus) in 100% of cases and normal acid pH (pH<4.5) in 98% of cases; it
      also fosters the disappearance of clue cells from vaginal smears and anaerobic
      pathogenic flora from vaginal secretions in 100% of cases. The amine test became
      negative in 97.8% of cases. All results underwent statistical analysis and were
      found to be statistically significant. CONCLUSION: Hydrogen peroxide represents a
      valid alternative to conventional treatments for recurrent bacterial vaginosis,
      and associates the absence of collateral effects with low costs, excellent
      tolerability and real therapeutic efficacy.

PMID- 14676738
TI  - [New and old procedures in the diagnosis of dubious breast lesions].
AB  - In the last years the detection of early breast cancers (lesions less than one
      centimetre in diameter, with good prognosis) has consistently increased for the
      wide application of mammary screening programs. At the same time, an increasing
      number of radiographically detected unexpected lesions (nonpalpable breast
      lesions) has been evidenced. In those cases, often both mammography and
      ultrasound evaluation are dubious and a multidisciplinary diagnostic approach is
      mandatory. Fine-needle aspiration (FNA) and core biopsy (CB) are well established
      diagnostic methods but, in recent years, new microinvasive bioptic procedures (as
      the Mammotome and the ABBI systems) have been introduced. In this review the
      limits and the possibilities of the classical and new cytohistological techniques
      are evaluated. A possible multistep diagnostic approach is described on a cost
      benefit basis and in consideration of the various procedures.

PMID- 14676739
TI  - [Acupuncture in labor management].
AB  - Acupuncture is being increasingly used in Western medical practice. The various
      applications of acupuncture during labor are reviewed in this paper. This ancient
      therapeutic technique can be employed with a significant percentage of positive
      results to induce labor in post-term pregnancies, to strengthen uterine
      contractility and to favour cervical maturation. The acupoints LI 4 Hegu e SP 6
      Sanyinjiao electrostimulated are those more frequently used in labor induction
      and in increasing the frequency and duration of uterine contractions. Moreover,
      our experience indicates that the acupoint BL 67 Zhiyin can be helpful in
      accelerating the dilation of the cervix: the treatment is effective in about 75%
      of patients. The studies on the use of acupuncture to achieve pain relief and
      analgesia during labor show more controversial results, mainly due to the great
      heterogeneity of applied treatments and some methodological biases. Nevertheless,
      the general evidence seems to be positive also for this application.

PMID- 14676740
TI  - No effect of HRT on health-related quality of life in postmenopausal women with
      heart disease.
AB  - AIM: Previous clinical studies suggest hormone replacement therapy (HRT)
      alleviates menopausal symptoms and may improve health-related quality of life
      (HRQL). Most studies on HRT and HRQL were limited in duration (12 months or less)
      and scope (few and non-standard HRQL measures). The aim of this paper is to
      assess HRQL in the Estrogen Replacement and Atherosclerosis (ERA) trial. METHODS:
      A subset of women within a randomized, blinded, placebo-controlled secondary
      prevention trial has been studied in outpatient and community settings at 5 US
      sites. A total of 246 postmenopausal women with angiographically documented heart
      disease (mean age 66 years, 83% Caucasian) were enrolled in the ERA trial.
      Participants received either 0.625 mg/day conjugated equine estrogen only,
      estrogen plus 2.5 mg/day medroxyprogesterone acetate, or placebo. HRQL was
      assessed using validated questionnaire instruments at baseline and follow-up
      (mean 3.2 years of trial). Physical and mental functioning, life satisfaction,
      depressive symptoms, urinary incontinence, sleep disturbance, and frequency and
      intensity of physical symptoms were evaluated. RESULTS: In this group of women
      with established coronary disease, active therapy was not significantly
      associated with more favorable outcomes for any HRQL. The estrogen-only group
      reported more urinary incontinence than the placebo group (p<0.05). Analyses
      restricted to adherent women (those who took > or = 80% of pills) showed a
      similar pattern of results, showing that the estrogen only group reported
      significantly higher urinary incontinence compared to placebo (p<0.01).
      CONCLUSION: The hormone replacement regimens in the ERA trial did not improve
      HRQL of postmenopausal women with heart disease.

PMID- 14676741
TI  - [External cephalic version for breech presentation at term: an effective
      procedure to reduce the caesarean section rate].
AB  - AIM: Although term breech presentation is a relatively rare condition (3-5% of
      all births), it continues to be an important indication for caesarean section and
      has contributed to its increased use. Risk of complications may be increased for
      both mother and foetus in such a situation. Vaginal delivery of a breech
      presenting foetus is complex and may involve many difficulties, so today there is
      a general consensus that planned caesarean section is better than planned vaginal
      birth for the foetus in breech presentation at term. External cephalic version is
      one of the most effective procedures in modern obstetrics. It involves the
      external manipulation of the foetus from the breech into the cephalic
      presentation. A successful manoeuvre can decrease costs by avoiding operative
      deliveries and decreasing maternal morbidity. The aim of the present study is to
      evaluate the effectiveness of this obstetric manoeuvre to increase the proportion
      of vertex presentation among foetuses that were formerly in the breech position
      near term, so as to reduce the caesarean section rate. The safety of the version
      is also showed. METHODS: From 1999 to 2002, 89 women with foetal breech
      presentation underwent external cephalic version at the Department of Obstetrics
      and Gynaecology of the Brescia University. The gestational age was 36.8+/-0.8
      weeks. The following variables have been taken into consideration: breech
      variety, placental location, foetal back position, parity, amount of amniotic
      fluid and gestational age. Every attempt was performed with a prior use of an
      intravenous drip of Ritodrine, and foetal heart rate was monitored continuously
      with cardiotocogram. RESULTS: The success rate of the procedure was 42.7% (n=38).
      No maternal or foetal complication or side effects occurred, both during and
      after the manoeuvre, except a transient foetal bradycardia that resolved
      spontaneously. Only one spontaneous reversion of the foetus occurred before
      delivery. Of all the women that underwent a successful version, 84.2% (n=32) had
      a non complicated vaginal delivery. Five women (15.8%) had a caesarean section.
      There was no significant interaction between the variables assessed. CONCLUSION:
      The external cephalic version is a safe and effective manoeuvre reducing the
      risks of vaginal breech delivery and the rate of caesarean section.

PMID- 14676742
TI  - Premature ovarian failure. Clinical evaluation of 32 cases.
AB  - AIM: Premature menopause, also termed premature ovarian failure (POF), is
      characterized by cessation of menstruation before the age of 40 years.
      Pathogenetic mechanisms are not so clear, particularly genetic implications of
      cellular apoptosis. Diagnostic approach is multifactorial and therapy depends on
      the pregnancy wish. METHODS: Eight hundred and thirty patients approached the
      Menopausal Center of the University Department of Gynaecological, Obstetrical and
      Reproductive Sciences of the Second University of Naples between October 1998 and
      October 2002. All patients were clinically investigated and selected on the basis
      of menopausal age, pregnancy wish and menopausal syndrome. RESULTS: Menopausal
      mean age was 48.31+/-4.62 years and 32 patients (4%) were affected by premature
      ovarian failure because of menopausal appearance before the age of 40. Three of
      these patients were treated to have a pregnancy; the remaining 29 required
      medical treatment to reduce menopausal symptoms. The osteoporosis risk for
      premature menopause patients was similar to the other women. The cardiovascular
      risk was increased because of an increase in risk factors in premature ovarian
      failure patients. No breast or endometrial pathology was revealed and therapy
      compliance was satisfactory without any drop-out. CONCLUSION: Premature ovarian
      failure has a varied etiology, pathogenetic aspects, clinical evolution and
      therapeutical approach. Adequate treatment of premature menopause women presents
      good compliance, resolution of infertility when required and a successful
      resolution of menopausal symptoms.

PMID- 14676743
TI  - Methotrexate treatment for tubal pregnancy. Criteria for medical approach.
AB  - AIM: The purpose of this retrospective study is to underline the indications for
      the use of systemic methotrexate (MTX) in tubal pregnancies. METHODS: One hundred
      and four (n=104) consecutive women were treated in our Department for tubal
      pregnancy. The database analysis showed that after careful respect for inclusion
      criteria, the treatment chosen was the intravenous administration of MTX in 68
      patients, whereas laparoscopy constituted the primary treatment in 36 patients. A
      single dose of MTX was intravenously administered, diluted in saline solution,
      with a dosage of 50 mg/m2 of body surface. Close serum beta-hCG monitoring was
      performed, and in the case of a short fall, a 2nd dose of methotrexate was
      submitted. RESULTS: The overall success rate of MTX treatment was 91%; the 2nd
      dose of MTX was used in 12% of patients, whereas in only 6 out of 68 patients
      included in the medical treatment group a surgical approach for suspected tubal
      rupture was necessary. CONCLUSION: Treatment with methotrexate is effective and
      safe in the presence of these criteria: patient hemodynamically stable, absence
      of tubal rupture sign and hemoperitoneum, an adnexal mass with a diameter < or =
      5 cm, an amenorrhea < or = 6 weeks and HCG levels < or = 10,000 mIU/ml.
      Laparoscopy is indicated in diagnostic uncertainty, when MTX is not suggested,
      when adnexal mass is > 5 cm, or in patients in which beta-hCG levels was > 10,000
      mIU/ml.

PMID- 14676744
TI  - [Successful outcome of pregnancy and vaginal delivery in a heart transplant
      recipient].
AB  - The case is reported of a patient subjected 4 years before conception to a heart
      transplant for biventricular hypertrophic myocardiopathy. The woman undertook and
      successfully concluded a pregnancy without complication and at the 37th week
      delivered spontaneously and vaginally. Four years after the birth both the woman
      and the newborn had suffered no after-effects. The choice and possibility for a
      transplant patient to face up to pregnancy and childbirth depend essentially,
      from a medical point of view, on her general state of health and on the presence
      or otherwise of other associated pathologies, in addition to the will of the
      patient to tackle the risks attached to her transplanted condition. It is
      therefore fundamental, in all cases, for such patients to undergo clear and
      detailed preconceptional counseling.

PMID- 14676745
TI  - [Topical imiquimod cream in the treatment of external anogenital warts: personal
      experience].
AB  - AIM: The clinical effects of home-therapy with 5% imiquimod cream in the
      treatment of cutaneous anogenital warts are evaluated. METHODS: From March 2000
      to January 2002, 57 women presenting clinical cutaneous external genital and
      perianal warts were selected in the base-population observed at our clinical of
      vulvar pathology and sexually transmitted diseases, AIED Rome. The patients were
      divided into 2 groups: Group A, with new cutaneous viral lesions and Group B with
      recurrent anogenital warts pre-treated with CO2-laser therapy. A total of 36%
      (20) of all patients presented contemporaneous HPV lesions of cervix and/or
      vaginal wall. The follow-up was carried out at 4 weeks, 3 months and 6 months,
      evaluating the safety, clinical efficacy and tolerance of women. The Pearson chi2
      test was used to evaluate trends significance. All lesions were photo-documented.
      RESULTS: Sixty-four per cent (64%) of the patients had complete clearance of
      anogenital warts within 16 weeks, for 3 times per week self-application of
      imiquimod, with clinical remission at short term (6/8 weeks) (chi2=1.42; p<0.05);
      12% had partial clearance (<50%) and 20% had a clearance of about 75%. The
      coexistent lesions of cervix and/or vaginal walls had a high remission (>50%) and
      required surgical additional therapy with CO2-laser; 28% of patients (16/57)
      experienced mild to moderate drug-related side effects. There was a significant
      increase in the severity of local skin reactions due to the increased time and
      number of applications. CONCLUSION: These data confirm that imiquimod cream at
      the dose regimen of 3 times per week, is effective and well tolerated in the
      treatment of cutaneous external warts and is associated to a reduction of
      coexistent mucous viral lesions due to enhancement of local immune response.

PMID- 14676746
TI  - Spectral and color M-mode Doppler in genetically altered mice. Assessment of
      diastolic function.
AB  - Doppler indices of transmitral flow are used commonly to assess noninvasively LV
      diastolic function in man and in large animals. This review examines
      echocardiographic indices of LV diastole (focusing on color M-mode) in mice with
      abnormal LV relaxation and hypertrophic cardiomyopathy based on genetic
      alterations of phospholamban and alpha-tropomyosin, respectively. Phospholamban
      (PLB) reversibly inhibits the sarcoplasmic reticulum Ca(2+) ATPase and is a
      crucial regulator of myocardial relaxation; tropomyosin is a contractile protein
      that plays a critical role in regulating contractile activity vis-a-vis
      interactions with the actin and troponin complex. Accordingly, diastolic function
      was assessed in PLB knockout mice (PLB/KO) and age-matched transgenic mice
      expressing a mutant, superinhibiting form of PLB (PLB/N27A), and in mice with
      cardiac-specific expression a mutant a-tropomyosin (TM-180). Transmitral Doppler
      flow indexes suggested impaired diastolic filling in the PLB/N27A mice, but
      improved LV diastolic function in the PLB/KO mice and TM-180 mutants. However,
      the propagation velocity of early flow into the LV cavity, measured by color M
      mode Doppler, confirmed the expected direction of altered LV relaxation in each
      mouse model. We conclude that transmitral filling patterns and color M-mode flow
      propagation velocity reflect changes in myocardial relaxation in genetically
      engineered mice, and may be useful tools to characterize LV diastolic function in
      other mouse models of disease.

PMID- 14676747
TI  - [Atrial septal defect and transesophageal echocardiography. From the diagnosis to
      the monitoring of transcatheter closure].
AB  - Atrial septal defect (ASD) is a common congenital heart disease representing 30%
      of congenital lesions in adults. Transcatheter closure has been regarded as an
      acceptable alternative treatment for patients with ASD. The prevalence of patent
      oval foramen (POF) is approximately 26% in autopsy and clinical studies, but it
      has been demonstrated that this prevalence is higher in patients with cryptogenic
      stroke. Even though the role of POF in the etiopathogenesis of cryptogenic stroke
      is debated, recurrent paradoxical embolism in the presence of POF associated with
      high motility of the membrane or with an atrial septal aneurysm is currently
      considered an indication for POF closure. This review covers the role of
      echocardiography (including transthoracic, transoesophageal and 3-dimensional
      methods) in the detection and diagnosis of these defects as well as the
      contribution of these techniques in the monitoring and follow-up of ASD and POF
      percutaneous closure.

PMID- 14676748
TI  - Real-time 3-dimensional echocardiography. Technique and clinical applications.
AB  - This article will provide an overview of real time 3-dimensional (3D)
      echocardiography (RT-3D) in evaluation of patients with heart disease. We will
      briefly describe the technique and our experience in its clinical applications in
      patients with coronary artery disease, left ventricular apical thrombi, mitral
      stenosis and its role in guiding intracardiac catheter placement. Our extensive
      experience with application of RT-3D during dobutamine stress and during supine
      bicycle exercise indicates the technique is sensitive in detection of ischemia.
      RT-3D has been valuable in clearly identifying left ventricular apical thrombi in
      patients in whom 2-dimensional (2D) echo cannot firmly establish their presence
      or absence. We have utilized RT-3D in guiding myocardial biopsy in heart
      transplant patients and in precisely measuring mitral valve area before and after
      balloon valvuloplasty. RT-3D technique continues to evolve and should play an
      important role in assessment of patients with heart disease.

PMID- 14676749
TI  - Three dimensional echocardiography and aortic valve stenosis.
AB  - Efforts have been made over the years to meet the challenge of three-dimensional
      (3D) reconstruction of cardiac structures. Succeeding in 3D reconstruction of the
      aortic valve and through it achieving better understanding and possibly better
      quantification of aortic stenosis severity is the main purpose of using such an
      imaging tool. The importance attached to it over the years is related mostly to
      the expectation of both clinicians and researchers not only for better and more
      complete imaging of its shape, but also for optimal demonstration of the valve
      motion and through it towards better understanding of valve function in health
      and disease. This review deals with 2 main aspects regarding 3D echocardiography:
      1). three-dimensional methods and general principles and 2). the special
      relevance of 3D reconstruction to the stenotic aortic valve.

PMID- 14676750
TI  - [Myocardial contrast echography. History, methodology and clinical applications].
AB  - Recent studies have demonstrated the usefulness of myocardial contrast
      echocardiography (MCE) in studying myocardial perfusion. Several first and second
      generation contrast agent such as Levovist, Sonovue, Optison, Definity and
      Imagent are commercially available or close to be introduced into the market. Use
      of MCE allowed the clinical demonstration of no-reflow phenomenon in patients
      with acute myocardial infarction (AMI) after recanalization of the infarct
      related artery (IRA). Coronary angiography is unable to assess the microvascular
      damage as showed by the poor correlation between TIMI grading and perfusion score
      evaluated by MCE. Furthermore, the use of MCE is important to determine coronary
      stenosis, to identify microvascular damage during ischaemia-reperfusion and to
      evaluate the presence of collateral circulation in the area at risk. MCE seems to
      be the most effective technique for assessing microvascular integrity after
      reperfusion as compared to TIMI myocardial perfusion grade, nuclear myocardial
      perfusion imaging and magnetic resonance imaging. These techniques are expensive,
      invasive and not available in most of the hospitals. Furthermore, as compared to
      nuclear medicine and echo-dobutamine, MCE has greater specificity and higher
      accuracy in detecting coronary artery disease. Recent studies showed that not
      only primary percutaneous coronary intervention (PCI) but also rescue and delayed
      PCI reduced microvascular damage and that MCE play a key role in assessing
      myocardial salvage after reperfusion. The most exciting aspect of MCE is the
      independent role in predicting left ventricular (LV) remodelling and functional
      recovery. The extent on no-reflow is an important predictor of LV dysfunction and
      remodelling at follow-up. Several studies have demonstrated that the extent of
      infarct-zone viability is a powerful independent predictor of LV dilation. There
      is a close relationship between the extent of microvascular damage, the extension
      of necrosis, the site of AMI and LV remodelling. We demonstrated that MCE
      performed 24 hours after reperfusion, at 1 week and 6 months appears to provide
      important prognostic information. These data support the daily use of MCE in
      coronary care unit and could establish a strategy for clinical decision making in
      patients with AMI.

PMID- 14676751
TI  - Myocardial contrast echocardiography for the assessment of left ventricular
      function.
AB  - Assessment of regional and global left ventricular (LV) function is important in
      the management of patients with known or suspected cardiovascular disease.
      Echocardiography is widely used to provide vital parameters of LV function such
      as ejection fraction, wall motion score indices, LV volumes and regional wall
      motion assessment. Despite advances in image quality some images may still be
      inadequate for accurate assessment of LV function. The advent of intravenous
      contrast agents consisting of microbubbles have allowed improved endocardial
      definition leading to better assessment of global and regional function. This
      together with advances in low power imaging techniques allow less microbubble
      destruction and hence smaller doses of contrast agent. Improved endocardial
      definition has also lead to advances in techniques for the automated
      quantification of LV function. As a result contrast enhanced echocardiography may
      become the gold-standard in the assessment of wall motion and LV function.

PMID- 14676752
TI  - Myocardial tissue Doppler echocardiography and cardiac resynchronization therapy.
AB  - Cardiac resynchronization therapy (CRT) is a promising technique for patients
      with end-stage, drug-refractory heart failure. Still 20-30% of the patients
      treated with CRT do not respond. Accordingly, the current selection criteria need
      to be refined, and it appears that demonstration of left ventricular dyssynchrony
      may be mandatory for response to CRT. Novel echocardiographic methods are
      currently investigated to detect left ventricular dyssynchrony and thereby
      improve the selection of candidates for CRT. In this brief review, these
      techniques will be discussed.

PMID- 14676753
TI  - The role of echocardiography in evaluation of the cardiac transplant recipient.
AB  - Echocardiography is an important tool in the management of cardiac transplant
      recipients. It provides comprehensive information about allograft structure and
      function without exposing the recipient to the risks associated with invasive
      investigations. Imaging can be performed in the early in-hospital phase and
      easily repeated during follow-up for the purposes of screening or for assessing
      the progression of specific pathology. When interpreting studies it is important
      to be aware that characteristic normal findings may be quite different from the
      non-transplant population. Endomyocar-dial biopsy remains the gold standard for
      the detection of acute allograft rejection. Doppler echocardiography has
      traditionally formed the basis for non-invasive diagnosis of this important
      complication but has recognised limitations. Advances in echocardiographic
      techniques indicate a potential important role for the reliable detection of
      rejection by this modality in the future. A range of other complications can be
      evaluated by echocardiography. There has been considerable recent interest in
      assessment of cardiac allograft vasculopathy by stress-imaging methods.

PMID- 14676755
TI  - Dental management of the patient with cardiac arrhythmias: an update.

PMID- 14676756
TI  - A prospective placebo-controlled double-blind trial of antibiotic prophylaxis in
      intraoral bone grafting procedures: a pilot study.
AB  - OBJECTIVE: A pilot study was conducted to assess the efficacy of a single-dose
      preoperative prophylactic of the penicillin pheneticillin compared with placebo
      in the antibiotic prophylaxis of surgical wound infections in intra-oral bone
      grafting procedures. PATIENTS AND METHODS: Twenty patients (age range 20-45
      years) underwent an intra-oral buccal onlay graft procedure. After randomization,
      a placebo or 2 grams of pheneticillin were administered orally one hour before
      surgery in a double-blind fashion. During three months, the postoperative course
      was observed according to clinical parameters of infection. Both groups were
      homogeneous in their composition and established risk factors for surgical wound
      infection. The frequency of surgical wound infections, as defined by the Centers
      of Disease control in 1992, were compared and evaluated statistically. RESULTS:
      Two patients developed a wound infection at the receptor site; two patients
      developed an infection at both the receptor and donor sites; and one patient
      developed an infection at the donor site only. All of these patients received a
      placebo. No infections were seen in the pheneticillin group. There was a
      statistically significant increased risk of having an infectious complication
      after an intra-oral bone graft without antibiotic prophylaxis. CONCLUSION: The
      results of this study support the efficacy of single-dose, preoperative, oral
      antibiotic administration.

PMID- 14676757
TI  - Levels of fibroblast growth factor 2 in synovial fluids in human patients with
      internal derangement of the temporomandibular joint.
AB  - OBJECTIVE: We sought to elucidate the levels of fibroblast growth factor 2 (FGF
      2) in synovial fluid taken from internally deranged human temporomandibular
      joints (TMJs) and to discuss the role of FGF-2 in the pathogenesis of internal
      derangement. STUDY DESIGN: Through the use of a pumping procedure, diluted
      synovial fluid was collected from the upper joint compartment of 22 TMJs with
      evidence of internal derangement (21 patients) and 8 TMJs with no such evidence
      (5 control subjects). Two of the control subjects were patients who had habitual
      dislocation, and three were healthy volunteers. The level of FGF-2 in the
      synovial fluid was assessed by means of an enzyme-linked immunosorbent assay.
      RESULTS: FGF-2 levels were at detectable levels in 15 of the 22 TMJs (68%) with
      internal derangement. The mean concentration of FGF-2 was 24 pg/mL. In the
      control group, FGF-2 levels were detectable in only 1 of 8 joints (13%), for a
      concentration of 3 pg/mL. The mean concentration of FGF-2 in the synovial fluid
      was significantly higher in the internal derangement group than in the control
      group (P =.02). CONCLUSIONS: FGF-2 levels are elevated in the human synovial
      fluid of TMJs with internal derangement.

PMID- 14676758
TI  - Ankylosis of the jaw in a patient with fibrodysplasia ossificans progressiva.
AB  - A case of fibrodysplasia ossificans progressiva (FOP) is presented. This uncommon
      connective tissue disease tends to produce progressing ectopic osteogenesis.
      Because there are no reported curative procedures for TMJ ankylosis occurring in
      this condition, a palliative surgical approach is described. Etiology, diagnosis,
      and prognosis of the disease is reviewed. Recent research in BMP cytokine-induced
      bone repair may allow new approaches to treating this debilitating disease in the
      future.

PMID- 14676759
TI  - The efficacy and safety of 50 mg penicillin G potassium troches for recurrent
      aphthous ulcers.
AB  - PURPOSE: To determine both the efficacy and safety of the topical application of
      50 mg penicillin G potassium troches (Cankercillin) in the treatment of minor
      recurrent aphthous stomatitis (RAS). STUDY DESIGN: The investigation used a phase
      2 double-blind, randomized placebo-controlled trial with a no-treatment arm.
      Subjects with minor aphthous ulcers of duration <48 hours were followed for 1
      week. The primary endpoint for efficacy was time (days) to complete ulcer
      resolution, and the secondary endpoint was time (days) to complete pain relief.
      RESULTS: Thirty-one, 33, and 36 subjects were randomized to the active treatment,
      placebo, and no-treatment arms, respectively. Baseline findings were
      heterogeneous across arms. Subjects who received penicillin G treatment had
      complete ulcer healing and pain relief significantly earlier than those in the
      placebo and no-treatment arms. No allergic reactions were observed. CONCLUSIONS:
      Topical penicillin G, by mechanisms which remain unclear, reduces the time of
      healing and pain relief of minor aphthous ulcers with minimal safety concerns.
      Larger phase 3 studies are necessary to confirm these findings.

PMID- 14676760
TI  - Dental infections and serum inflammatory markers in patients with and without
      severe heart disease.
AB  - OBJECTIVE: The objective of this study was to investigate if patients with severe
      heart disease (CHD patients) present more signs of dental infections than
      patients without heart disease (non-CHD patients), if serum inflammatory markers
      differ between the groups, and if there is a link between these and the oral
      health parameters. METHODS: We performed clinical and radiologic dental
      examinations and collected serum samples of 256 patients with New York Heart
      Association class II-IV heart disease (CHD patients) and 250 non-CHD controls.
      Serum samples were analysed using pertinent methods in the clinical laboratory of
      the hospital, and the differences in serum biomarkers between CHD patients and
      non-CHD patients were examined using various statistical methods. A modified
      dental index (MDI) was constructed and used in the analyses. RESULTS: CHD
      patients were significantly more likely to be edentulous (34.8% vs. 14.8%) and
      retain less natural teeth than non-CHD patients (8.6 vs. 17) (P <.001). In CHD
      patients the remaining teeth and supporting tissues were more often diseased.
      High MDI scores were significantly associated with CHD status (OR 1.31, CI 1.16
      1.48), as was gingivitis (OR 3.37, CI 1.66-6.86), while the presence of deep
      periodontal pockets was not. Serum C-reactive protein and fibrinogen
      concentrations and blood erythrocyte sedimentation rates were higher in the CHD
      group. Also, H. pylori and Chlamydia antibodies were significantly higher in the
      CHD group. CONCLUSION: CHD patients presented with poorer oral health status than
      non-CHD patients. Serum inflammatory markers were significantly higher in the CHD
      patients compared to the non-CHD group. High MDI scores linked with risk of CHD.

PMID- 14676761
TI  - Oral Kaposi's sarcoma: a clinicopathologic study from South Africa.
AB  - OBJECTIVES: In this retrospective study, we defined the clinicopathologic
      characteristics of oral Kaposi's sarcoma (KS) and determined the presence of
      human herpesvirus 8 in the oral lesions in a group of South African patients.
      These results were compared with similar data from patients in developed
      countries. STUDY DESIGN: Eighty-one cases of oral KS were retrieved from the
      departmental archives. Fourteen patients with oral pyogenic granuloma served as
      control subjects. DNA was extracted by using a modified phenol chloroform
      extraction method and amplified by using polymerase chain reaction. If beta
      globin DNA sequences could not be demonstrated, the patient was excluded from the
      study. RESULTS: Of the 81 patients included in the study, 68 (84%) had been
      diagnosed since 1997. Oral KS was often the first presenting sign of human
      immunodeficiency virus infection. Some of the lesions exceeded 4 cm in diameter.
      The most commonly affected site was the palate (37 patients), followed by the
      tongue and gingiva. Multiple oral sites were frequently involved. The mean age of
      the patients was 34.7 years (range, 2-58 years). The male-to-female ratio was
      1.31 to 1. Most of the patients (94%) were black. Human herpesvirus 8 DNA
      sequences were detected in 44 of the 45 cases of oral KS in which the DNA was
      analyzed, and in 1 case of pyogenic granuloma. CONCLUSIONS: The only significant
      clinicopathologic differences in findings between our study and previous studies
      in developed countries were (1) the male-to-female ratio, (2) the preponderance
      of black patients, and (3) the more frequent involvement of the tongue. There are
      no studies reporting the clinicopathologic characteristics of oral KS in
      populations of developing countries.

PMID- 14676762
TI  - Histopathologic comparison of normal and hyperplastic condyles.
AB  - OBJECTIVE: The aim of this study was to compare normal and hyperplastic
      mandibular condyles using two different histopathologic staining techniques.
      STUDY DESIGN: Nine cases of condylar hyperplasia and 13 normal cases were studied
      after hematoxylin and eosin and silver staining. RESULTS: There was a significant
      difference between the two groups in the thickness of the hyperplastic cartilage
      layer of condylar soft tissue (P = 0.017). Also, the number of argyrophilic
      nucleolar organizer regions was significantly higher in the condylar hyperplasia
      case group (P = 0.0001). No significant differences could be demonstrated in
      cartilage island frequency, penetration depth, and distribution in the cancellous
      bone of condyles. CONCLUSION: The thickness of the hyperplastic cartilage layer
      appears significantly increased in condylar hyperplasia. In addition,
      argyrophilic nucleolar organizer region count may be useful in histopathological
      identification of condylar hyperplasia.

PMID- 14676763
TI  - Chronic ulcerative stomatitis: clinical, histopathologic, and immunopathologic
      findings.
AB  - Chronic ulcerative stomatitis (CUS) is a mucocutaneous disease primarily
      involving mucosal surfaces, but occasionally may involve the skin. Clinically,
      CUS patients exhibit erosive or ulcerative lesions of the oral mucosa that
      resemble erosive oral lichen planus. Direct immunofluorescence (DIF) studies of
      mucosal or skin biopsies reveal a unique pattern of IgG immunoglobulin bound to
      nuclei of keratinocytes of the basal and lower one third cell layers, the
      stratified epithelial specific (SES) antinuclear antibody (ANA) pattern. Patient
      sera also exhibit circulating SES-ANA reactions on indirect immunofluorescence
      (IIF) using an esophagus substrate. We report the clinical and immunopathologic
      findings of 3 cases of CUS and demonstrate autoantibody recognition of the CUS
      antigen on Western blot. An important reason to distinguish CUS from other oral
      ulcerative conditions is that it may be refractory to standard treatments with
      topical corticosteroids, and favorable clinical responses may be achieved with
      hydroxychloroquine pharmacotherapy.

PMID- 14676764
TI  - Oncocytic mucoepidermoid carcinoma of parotid gland origin.
AB  - This article reports 3 cases of oncocytic mucoepidermoid carcinoma of the parotid
      gland and compares them with 9 cases from the literature with emphasis on
      clinical behavior, treatment, and recurrence rate. The tumor occurs most often in
      the middle-aged to elderly, with a decided predilection for the parotid gland.
      All three oncocytic mucoepidermoid carcinomas from the Armed Forces Institute of
      Pathology series were low grade with extensive oncocytic change. Treatment
      modalities consisted of superficial parotidectomy, total parotidectomy, or total
      parotidectomy. The mean follow-up interval was 5.5 years. Only one case from the
      literature, a high-grade mucoepidermoid carcinoma, recurred. Results of this
      study indicate that the parotid gland oncocytic mucoepidermoid carcinoma behaves
      in a fashion similar to typical mucoepidermoid carcinoma, with prognosis
      dependent on clinical stage, histopathologic grade, and adequacy of treatment.
      Recognizing the spectrum of oncocytic differentiation in salivary gland tumors
      will serve to establish appropriate diagnoses and treatment.

PMID- 14676765
TI  - Displaced calcium hydroxide paste causing inferior alveolar nerve paraesthesia:
      report of a case.
AB  - A patient presented with an intraoral red, painful, and hard swelling in the
      lower right jaw. Radiographs showed a 2 x 1 cm area of radiopaque material
      surrounding the apex of the second premolar. The material, according to the
      patient's dentist, was calcium hydroxide paste used as a temporary dressing
      material in the root canal. The patient developed paraesthesia in her lower lip
      probably due to a neurotoxic effect caused by calcium hydroxide. The foreign
      material was surgically excavated from the spongious bone, directly adjacent to
      the nerve, and the patient later regained her sensation in the lip. A
      histopathological analysis revealed necrosis, deposits of foreign bodies, and
      inflammatory cells and foreign-body giant cells. This report illustrates the
      toxicity and adjacent clinical symptoms of calcium hydroxide paste when displaced
      into bone tissue close to the alveolar inferior nerve. It also demonstrates the
      benefits of removing such displaced material before symptoms progress.

PMID- 14676766
TI  - The synergistic effect of peptidoglycan and lipopolysaccaride on osteoclast
      formation.
AB  - PURPOSE: The purpose of this study was to investigate the mechanisms leading to
      periapical tissue destruction by the Gram-positive bacterial cell component,
      peptidoglycan (PGN) and Gram-negative bacterial cell component lipopolysaccaride
      (LPS). STUDY DESIGN: Osteoclast precursor RAW 264.7 cells were cultured with 50
      ng/ml receptor activator of NF-kappaB ligand (RANKL) for 72 hours. RANKL was then
      removed and the cells were treated with various concentrations of PGN in the
      presence or absence of various concentration of LPS for an additional 48 hours.
      RT-PCR analysis was performed to examine the presence of receptors on osteoclasts
      known to be involved in mediating cellular activation in response to PGN (TLR2)
      and LPS (TLR 4). RESULTS: PGN dose dependently and reproducibly stimulated TRAP
      positive multinucleated osteoclast-like (OCL) cell formation. PGN and LPS had
      synergistic effects on the induction of OCL cell formation. Both unstimulated and
      RANKL-stimulated RAW 264.7 cells expressed TLR2 and TLR4 mRNA. CONCLUSION: The
      results underscore the importance of considering both Gram-positive and Gram
      negative bacteria when interpreting findings associated with primary and
      secondary periapical lesions.

PMID- 14676767
TI  - Evaluation of the antibacterial potential of tetracycline or erythromycin mixed
      with calcium hydroxide as intracanal dressing against Enterococcus faecalis in
      vivo.
AB  - OBJECTIVE: We evaluated the intracanal antibacterial potential of tetracycline or
      erythromycin mixed with calcium hydroxide (CH) against enterococci in vivo. STUDY
      DESIGN: Fifty-five teeth in which enterococci were present were dressed for 1
      month with either tetracycline (28 teeth) or erythromycin (27 teeth) mixed with
      CH. RESULTS: The tetracycline mixture was effective against enterococci in 22
      teeth (79%). In 7 teeth, other microorganisms were recovered, resulting in a
      total antimicrobial effect of 54%. The corresponding results for erythromycin
      were 96% and 56%. CONCLUSIONS: The antimicrobial treatment of CH in combination
      with either erythromycin or tetracycline had a significant effect on enterococci,
      but the overall antimicrobial effect was relatively weak. Erythromycin mixed with
      CH seems to be a valuable option in the battle against monoinfections of
      enterococci.

PMID- 14676768
TI  - Reduction of viable bacteria in dentinal tubules treated with clindamycin or
      tetracycline.
AB  - AIM: We sought to evaluate and compare the antibacterial effect of clindamycin
      and tetracycline in bovine dentinal tubules. METHODS: Dentinal tubules of 32
      cylindrical bovine root specimens were infected with Streptococcus sanguis N1.
      Clindamycin 2% or tetracycline 2% (Ledermix) was placed in the root canal for 1
      week. Powder dentin samples obtained from within the canal lumina by using
      International Standards Organization No. 25 to No. 31 burs were examined for the
      presence of vital bacteria after the brain-heart infusion plates were inoculated
      and the colony-forming units were counted. The potent effect of the medicaments
      was also evaluated through the use of the agar diffusion test. RESULTS: Heavy
      bacterial infection was observed in the control bovine root specimens at the
      layer close to the lumen. This decreased rapidly from layer to layer up to the
      deepest layer tested (300-400 microm), which contained several hundred colony
      forming units. Clindamycin significantly reduced the amount of viable bacteria in
      each dentin layer compared with the positive control and tetracycline (P <.01).
      The agar diffusion test, wherein dilutions in increments of 1/3 and 1/9 were
      used, revealed that both medicaments had antibacterial activity, but clindamycin
      was significantly better. In the 1/27 dilution, clindamycin had a minor effect
      and tetracycline had no effect at all. CONCLUSION: Under the experimental
      conditions used in this study, the commercial preparations of clindamycin were
      more effective than those of tetracycline (Ledermix) in the agar diffusion test
      and clindamycin penetrated into dentinal tubules up to 400 microm. Thus, it has
      the potential to serve as an effective intracanal medicament in persistent
      infections when other medicaments fail.

PMID- 14676769
TI  - Bending properties of rotary nickel-titanium instruments.
AB  - OBJECTIVE: We sought to compare the bending properties of different rotary nickel
      titanium instruments and to investigate the correlation between their bending
      moments and their cross-sectional surface areas. STUDY DESIGN: Resistance to
      bending was determined according to International Standards Organization
      publication 3630-1. The sample size was 10 files for each type, taper, and size.
      The cross-sectional surface area of all instruments was determined by using
      scanning electron microscope photographs of the cross section. The images were
      scanned and the area was calculated by using special software. Data were analyzed
      by using analysis of variance and the Student t test and the Newman-Keuls test
      for all pairwise comparisons. The strength of the correlation between the bending
      moment and the cross-sectional area was determined by computing the Pearson
      product moment correlation. RESULTS: Bending moments were significantly lower for
      ProFile and RaCe files than for all other files (P <.05). K3 files were
      significantly less flexible than all other instruments (P <.05). The correlation
      between stiffness and cross-sectional area was highly significant (r = 0.928; P
      <.0001). CONCLUSION: Nickel-titanium files with tapers greater than.04 should not
      be used for apical enlargement of curved canals because these files are
      considerably stiffer than are those with.02 or.04 tapers.

PMID- 14676770
TI  - Visibility of trabecular structures in oral radiographs.
AB  - OBJECTIVES: To determine whether alveolar trabecular bone is visible and
      quantifiable in projection radiographs. Radiographic changes in oral trabecular
      bone have been studied as possible indications of bone loss, but in some previous
      studies, observed structures have been attributed entirely to the endosteal
      surface. METHODS: Computed radiography (CR) images of human mandibles in molar
      and pre-molar regions were compared with simulations calculated from high
      resolution computed-tomography (CT) and micro-CT volumes. By digitally editing
      the CT volumes, the simulations were separated into trabecular and cortical
      components. High-pass-filtered CR images revealed structural details of cortical
      and trabecular bone. RESULTS: Trabecular bone constitutes as much as 38% of the
      total alveolar bone, and accounts for most of the observed alveolar fine
      structure. Several morphological types of fine structure can be distinguished.
      The noise in filtered images appears to be a meaningful measure of trabecular
      bone. CONCLUSION: Trabecular bone is highly visible in intraoral radiographs.

PMID- 14676771
TI  - Brief communication: Bone trabeculae are visible on periapical images.
AB  - It is traditionally believed that the radiographic image of bone striae is a
      reflection of the trabecular pattern of cancellous bone. Results of a 1999 paper
      by Cavalcanti et al. contradicted this paradigm, suggesting that the intraoral
      radiographic image of trabecular pattern in the mandible reflects the morphology
      of the endosteal surface of the cortical bone, rather than that of cancellous
      bone. Here, we conduct a simple experiment to assess the contribution of dry
      mandibular cancellous bone to the image of trabecular pattern seen on intraoral
      films. Standardized periapical-type radiographs centered on the same region of
      interest of a dry human mandible were acquired before and after removal of the
      buccal, then of both cortical plates, together with the endosteal cortical
      trabecular bone interface. One oral and maxillofacial radiologist and 4 oral and
      maxillofacial radiology residents blindly assessed the presence or absence of
      bone striations on the acquired images. We find that bone striations are visible
      on periapical-type images of dry human mandibles in the absence of one or both
      cortical plates, and that their pattern is similar to that seen in the image of
      the intact specimen. We conclude that cancellous bone contributes significantly
      to the image of trabecular bone in dry human mandibles.

PMID- 14676772
TI  - The correlation of histologic features with a panoramic radiography pattern and a
      computed tomography pattern of bone destruction in carcinoma of the mandibular
      gingiva.
AB  - OBJECTIVE: We sought to clarify the correlation among a computed tomography (CT)
      or a panoramic radiography (PR) pattern of bone destruction, a histologic pattern
      of bone destruction, and a mode of invasion in carcinoma of the mandibular
      gingiva. STUDY DESIGN: CT images, panoramic radiographs, and decalcified,
      hematoxylin-eosin-stained preparations of the excised mandibular bone of 62
      patients with carcinoma of the mandibular gingiva were retrospectively evaluated.
      Each computed tomograph, panoramic radiograph, and the histologic pattern of bone
      destruction was classified as 1 of 5 types: erosive, erosive and partly mixed,
      mixed, mixed and partly invasive, or invasive. The mode of invasion of the tumor
      was also assessed with a hematoxylin-eosin-stained preparation of the initial
      biopsy specimen. The relationships among the CT pattern, the PR pattern, the
      histologic pattern of bone destruction, and the mode of invasion of the tumor
      were statistically analyzed by using the Spearman rank correlation test. RESULTS:
      The CT pattern (P =.005) and the PR pattern (P =.003) were significantly
      correlated with the histologic pattern with respect to the bone destruction. The
      CT pattern (P =.996), the PR pattern (P =.997), and the histologic pattern (P
      =.521) of bone destruction were not correlated with the mode of invasion seen in
      the biopsy specimen. CONCLUSION: The CT pattern and the PR pattern of bone
      destruction reflect the histologic pattern of bone destruction caused by
      carcinoma of the mandibular gingiva but are not associated with the mode of
      invasion of the tumor.

PMID- 14676774
TI  - Urgent need for a validated tumor response evaluation system for use in
      immunotherapy.

PMID- 14676775
TI  - Clinical significance of cytomegalovirus (CMV) antigenemia in the prediction and
      diagnosis of CMV gastrointestinal disease after allogeneic hematopoietic stem
      cell transplantation.
AB  - To evaluate the clinical significance of a cytomegalovirus (CMV) antigenemia
      assay in the prediction and diagnosis of CMV gastrointestinal (CMV-GI) disease
      after hematopoietic stem cell transplantation (HSCT), 19 allogeneic HSCT
      recipients developing CMV-GI disease were retrospectively reviewed. All patients
      were monitored by a CMV antigenemia assay, at least once weekly after
      engraftment. The median onset of CMV-GI disease occurred 31 days post transplant
      (range: 19-62). Only four of 19 patients (21%) developed a positive CMV
      antigenemia test before developing CMV-GI diseases. Although all 19 patients
      subsequently developed positive CMV antigenemia tests during their clinical
      courses, the values remained at a low-level in nine (47%) patients. Among the 14
      patients in whom results of real-time polymerase chain reaction (PCR) were
      available, seven (50%) yielded positive results of real-time PCR before
      developing CMV-GI disease. In contrast to the values of CMV antigenemia, all 14
      patients exclusively yielded high viral loads (median: 2.8 x 10(4) copies/ml
      plasma). We conclude that CMV antigenemia testing has limited value in prediction
      or early diagnosis of CMV-GI disease, and that real-time PCR could have a more
      diagnostic significance.

PMID- 14676776
TI  - Autologous stem cell transplantation in adult patients with peripheral T-cell
      lymphoma: a nation-wide survey.
AB  - Limited experience is available on the feasibility and efficacy of high-dose
      therapy (HDT) supported by autologous stem cell transplantation (ASCT) in
      patients with peripheral T-cell lymphoma (PTCL). Therefore, a nation-wide survey
      was conducted in adult patients transplanted for PTCL in Finland during 1990
      2001. After histopathology review, 37 patients were identified. The median age
      was 46 years (16-68) at the time of ASCT. Histology included PTCL not otherwise
      specified in 14 patients, anaplastic large cell lymphoma (ALCL) in 14 patients,
      and other in nine patients. Disease status at the time of ASCT was CR/PR1 in 18
      patients; CR/PR2 in 14 patients, and other in five patients. HDT consisted of
      either BEAC (N=22) or BEAM (N=15), supported by blood stem cells in 34 patients
      (92%). Early transplant-related mortality was 11%. With a median follow-up of 24
      months from HDT, 16 patients (43%) have relapsed or progressed. The estimated 5
      year overall survival (OS) was 54%. Patients with ALCL had superior OS when
      compared with other subtypes (85 vs 35%, P=0.007). OS at 5 years was 63% in
      patients transplanted in CR/PR1 vs 45% in those transplanted in other disease
      status (P=NS). Prospective studies are needed to define the role of ASCT in this
      lymphoma type.

PMID- 14676777
TI  - Pure red cell aplasia after a major ABO-mismatched bone marrow transplant for
      chronic myeloid leukaemia: response to re-introduction of cyclosporin.

PMID- 14676778
TI  - Hematopoietic stem cell donor registry strategies for assigning search
      determinants and matching relationships.
AB  - Registries and cord blood banks around the world collect and store the HLA types
      of volunteers in order to identify matched unrelated donors for patients
      requiring hematopoietic stem cell transplantation. This task is complicated by
      the many formats in which HLA types are provided by the testing laboratories
      (types obtained by serology vs by DNA-based methods; high vs intermediate vs low
      resolution) and by the need to identify which of these diverse types are most
      likely to match the HLA assignments of a searching patient as closely as
      possible. Conversion of the assignments to 'search determinants' may be included
      within the algorithm used to select and prioritize a list of potentially suitable
      donors, either as an aid to matching or as a tool to optimize the performance of
      comparisons within large data files. The strategies used by registries to create
      search determinants are described. A set of search determinants, utilized by the
      National Marrow Donor Program, is provided as an example and is intended to
      initiate further discussion aimed at understanding the process used by each
      registry with the possibility of developing a standard process among registries
      worldwide.

PMID- 14676779
TI  - Glutamine parenteral supplementation in stem cell transplant.

PMID- 14676780
TI  - Expression of TNFalpha by CD3+ and F4/80+ cells following irradiation
      preconditioning and allogeneic spleen cell transplantation.
AB  - The pathogenesis of acute graft-versus-host disease (aGVHD) includes tumor
      necrosis factor-alpha (TNFalpha) expression by macrophages and T cells. However,
      the temporal comparison of donor vs host cells to TNFalpha expression in response
      to irradiation conditioning and alloreactivity has not been reported. This study
      compared intracellular TNFalpha expression in donor vs host spleen T cells and
      macrophages using a murine model of aGVHD. Total body irradiation conditioning
      alone resulted in increased frequency of F4/80+/TNFalpha+ cells, but no increase
      in CD3+/TNFalpha+ cells. Syngeneic transplantation resulted in an increased
      frequency of F4/80+/TNFalpha+ cells, while CD3+/TNFalpha+ cells increased on days
      1 and 3 but declined on day 5. Allogeneic transplantation resulted in an
      increased frequency of donor CD3+/TNFalpha+ cells, while the frequency of host
      CD3+/TNFalpha+ cells declined. Similarly, donor F4/80+/TNFalpha+ cells also
      increased in frequency after allotransplantation, while the frequency of host
      F4/80+/TNFalpha+ cells was increased on day 1 and declined through days 3 and 5.
      In absolute cell numbers, CD3+/TNFalpha+ cells were greater than F4/80+/TNFalpha+
      cells post allotransplantation. We conclude that (1) both donor and host CD3+ and
      F4/80+cells are present in the post transplant period and contribute to TNFalpha
      production and (2) in terms of frequency, the majority of TNFalpha producing
      cells in the spleen after allogeneic BMT are CD3+.

PMID- 14676781
TI  - Outcome of transplantation with unrelated donor bone marrow in children with
      severe thalassaemia.
AB  - SUMMARY: We conducted a study of unrelated donor bone marrow transplantation
      (BMT) in 11 children with severe thalassaemia. The conditioning regimen consisted
      of busulphan, cyclophosphamide and antilymphocyte globulin. All received T-cell
      nondepleted bone marrow. The median marrow-nucleated cell dose was 4.9 x 10(8)
      /kg (range; 3.5-8.0 x 10(8) /kg). Median time of granulocyte recovery was 16 days
      (range; 13-21 days), and of platelet recovery was 39 days (range; 14-196). Grade
      2-4 acute graft-versus-host disease (GVHD) developed in six patients (54%), and
      grade 3-4 in one patient (9%). Three (27%) of 11 evaluable patients had chronic
      GVHD (limited stage). All 11 patients are alive without thalassaemia after a
      median follow-up time of 397 days (range; 171-814 days). This study lends support
      to consideration of unrelated donor BMT as an acceptable therapy to cure severe
      thalassaemia especially in patients who are young and do not yet show
      irreversible severe complications of iron overload.

PMID- 14676783
TI  - Efficacy and safety of femoral vascular access for peripheral blood stem cell
      (PBSC) collection.
AB  - Central venous catheters are frequently used in leukapheresis to provide high
      flow rates. The most common locations are the subclavian or jugular vein, but
      insertion-related complications and inadequate flow are frequent problems.
      Experience using femoral venous access is limited, because this has been
      discouraged due to the high incidence of infectious or thromboembolic
      complications. We evaluated the safety and efficacy of 108 short-term femoral
      venous dialysis catheters used for the collection of peripheral blood stem cells
      (PBSCs). All catheters were placed by a member of the dialysis unit, and they
      remained in situ for the days needed to reach the target number of CD34+cells. No
      prophylactic antibiotic or antithrombotic therapy was used. A total of 232
      apheresis sessions was performed. The longest duration a catheter remained in
      situ was 5 days. Most of the patients finished the collection in one or two
      apheresis sessions. There were no thrombotic or infectious complications, and
      insertion-related complications or mechanical problems were minimal. Apheresis
      results were similar to those reported using subclavian or jugular venous access.
      The short-term use of femoral venous dialysis catheters appears safe and
      effective for PBSC collection, simplifying the procedure, improving patient
      comfort, and reducing cost.

PMID- 14676782
TI  - Effective donor lymphohematopoietic reconstitution after haploidentical CD34+
      selected hematopoietic stem cell transplantation in children with refractory
      severe aplastic anemia.
AB  - Peritransplant toxicity and a delay in effective immune reconstitution have
      limited the utility of alternate donor transplantation for children with
      refractory severe aplastic anemia. We have assessed the effectiveness of infusing
      large numbers of highly purified haploidentical CD34+ cells after immunoablative
      conditioning in three patients who had failed intensive immunosuppression, lacked
      unrelated donors, and had active or recent serious infections. One patient
      rejected the first infusion, but engrafted after a second infusion from the same
      donor. This patient died 4 months after hematopoietic stem cell transplantation
      with no evidence of lymphoid reconstitution. Two patients experienced mixed
      chimerism requiring treatment with antibodies and/or donor lymphocyte infusion.
      Both currently survive more than 1 year after transplantation with normal blood
      counts, 100% donor engraftment, effective lymphoid reconstitution, and no chronic
      graft-versus-host disease. We observed functional thymopoiesis as measured by
      lymphocyte immunophenotyping, T cell receptor excision circles and T cell
      receptor Vbeta spectratyping complexity analysis. Further study is required to
      validate the initial promise of these preliminary observations.

PMID- 14676784
TI  - Infused peripheral blood autograft absolute lymphocyte count correlates with day
      15 absolute lymphocyte count and clinical outcome after autologous peripheral
      hematopoietic stem cell transplantation in non-Hodgkin's lymphoma.
AB  - Absolute lymphocyte count at day 15 (ALC-15) after autologous peripheral blood
      hematopoietic stem cell transplantation (APHSCT) is an independent prognostic
      factor for survival in non-Hodgkin's lymphoma (NHL). Factors affecting ALC-15
      remain unknown. We hypothesized that dose of infused autograft lymphocytes (A
      ALC) directly impacts upon ALC-15. A total of 190 consecutive NHL patients
      received A-ALC between 1993 and 2001. The primary end point was correlation
      between A-ALC and ALC-15. A strong correlation was identified (r=0.71). A higher
      A-ALC was infused into patients achieving an ALC-15 > or =500/microl vs ALC-15
      <500/microl (median of 0.68 x 10(9)/kg (0.04-2.21 x 10(9)/kg), vs 0.34 x 10(9)/kg
      (0.04-1.42 x 10(9)/kg), P<0.0001). The median follow-up for all patients was 36
      months (maximum of 109 months). The A-ALC threshold was determined at 0.5 x
      10(9)/kg. The median overall survival (OS) and progression-free survival (PFS)
      times were longer in patients who received an A-ALC >/=0.5 x 10(9)/kg vs A-ALC
      <0.5 x 10(9)/kg (76 vs 17 months, P<0.0001; 49 vs 10 months, P<0.0001,
      respectively). Multivariate analysis demonstrated A-ALC to be an independent
      prognostic indicator for OS and PFS. These data support our hypothesis that ALC
      15 and survival are dependent upon the dose of infused A-ALC in NHL.

PMID- 14676785
TI  - In vitro monitoring of endothelial complications following hematopoietic
      allogeneic stem cell transplantation.

PMID- 14676786
TI  - CD34 selection for bone marrow transplants for children with genetic diseases.

PMID- 14676787
TI  - High-dose intravenous melphalan and autologous stem cell transplantation as
      initial therapy or following two cycles of oral chemotherapy for the treatment of
      AL amyloidosis: results of a prospective randomized trial.
AB  - SUMMARY: A prospective randomized trial was conducted to study the timing of high
      dose intravenous melphalan and autologous stem cell transplantation (HDM/SCT) in
      AL amyloidosis. In all, 100 newly diagnosed patients were randomized to receive
      HDM/SCT, either as initial therapy (Arm-1) or following two cycles of oral
      melphalan and prednisone (Arm-2). The objectives of the trial were to compare
      survival and hematologic and clinical responses. With a median follow-up of 45
      months (range 24-70), the overall survival was not significantly different
      between the two treatment arms (P=0.39). The hematologic response and organ
      system improvements after treatment did not differ between the two groups. Fewer
      patients received HDM/SCT in Arm-2 because of disease progression during the oral
      chemotherapy phase of the study, rendering them ineligible for subsequent high
      dose therapy. This affected patients with cardiac involvement particularly, and
      led to a trend for an early survival disadvantage in Arm-2. Hence, newly
      diagnosed patients with AL amyloidosis eligible for HDM/SCT did not benefit from
      initial treatment with oral melphalan and prednisone, and there was a survival
      disadvantage for patients with cardiac involvement if HDM/SCT was delayed by
      initial oral chemotherapy.

PMID- 14676788
TI  - Drug interactions in the hematopoietic stem cell transplant (HSCT) recipient:
      what every transplanter needs to know.
AB  - Pharmacokinetic drug interactions among hematopoietic stem cell transplant
      recipients can result in either increases in serum concentrations of medications,
      which may lead to enhanced toxicity; or reduced serum concentrations, which can
      lead to treatment failure and the emergence of post transplant complications. The
      use of drugs that have a narrow therapeutic index, such as
      cyclosporine/tacrolimus (calcineurin inhibitors), increases the significance of
      these interactions when they occur. This report will review the clinical data
      evaluating the drug interactions of relevance to HSCT clinical practice, focusing
      on the pharmacokinetic interactions, and provides recommendations for managing
      these interactions to avoid both toxicity and treatment failure.

PMID- 14676789
TI  - Stamping out cancer.
AB  - It is universally acknowledged that if cancer is to be controlled, prevention and
      down staging are essential. In the year 2000 about 10 million new cases were
      registered, while 6.3 million people died from cancer worldwide. Stamps are
      regarded as a very useful and educative tool in fighting cancer by creating
      awareness and raising money for treatment and research. This year (2003) is the
      seventy-fifth anniversary of the issue of the first anticancer stamps in 1928, so
      an up-to-date review of the field of oncophilately is timely.

PMID- 14676790
TI  - Applications of array technology: identification of molecular targets in bladder
      cancer.
AB  - High-throughput microarrays are being used in expression profiling analyses with
      the objectives of gene and pathway discovery, functional characterization of
      genes, and tumor subclassification. This review summarizes bladder cancer studies
      dealing with both in vitro models and clinical specimens, using distinct
      microarray platforms for target discovery.

PMID- 14676791
TI  - Progress in treatment of small-cell lung cancer: role of CPT-11.
AB  - Small-cell lung cancer (SCLC) accounts for approximately 15% of all cases of lung
      cancer and is a particularly aggressive form of lung cancer characterised by a
      poor prognosis, rapid tumour growth, and early metastasis. Roughly, two-thirds of
      patients with SCLC present with extensive disease (ED) and one-third with limited
      disease (LD). Combination chemotherapy is the most effective treatment modality
      for SCLC, and several new agents, including carboplatin, ifosfamide, taxans, and
      topotecan, have been demonstrated to be active; however, there are no data on the
      survival benefit of these drugs. A CPT-11+ cisplatin regimen has shown
      improvement in overall survival over the global gold standard regimen, etoposide
      + cisplatin (Japanese Clinical Oncology Group: JCOG 9511), and three confirmatory
      randomised controlled trials are in progress to determine the reproducibility of
      the JCOG 9511 study. JCOG is evaluating the role of CPT-11 and a new triplet
      regimen containing CPT-11 in limited-stage SCLC. Strategies and the current
      protocols of the JCOG are presented and discussed. In the future, it will be
      essential to evaluate molecular target-based drugs for LD and ED SCLC with new
      standard combination chemotherapy regimens that include CPT-11.

PMID- 14676792
TI  - Accelerated regrowth of non-small-cell lung tumours after induction chemotherapy.
AB  - Induction chemotherapy of non-small-cell lung cancer (NSCLC) stage III with
      gemcitabine and cisplatin for downstaging of the tumour with the aim for further
      treatment with ionising radiation is one of the treatments for lung cancer
      patients. The purpose of this study was to investigate the influence of the
      waiting time for radiotherapy, that is, the interval between induction
      chemotherapy and radiotherapy, on the rate of tumour growth for patients with
      NSCLC. Interval times between the end of induction chemotherapy and date of
      diagnostic CT, planning CT and first day of radiotherapy were determined for 23
      patients with NSCLC. Increase in gross tumour volume was measured for 18 patients
      by measuring the dimensions of the primary tumour and lymph node metastases on
      the diagnostic CT after induction chemotherapy and on the CT used for
      radiotherapy planning. For each patient, the volume doubling time was calculated
      from the time interval between the two CTs and ratio of the gross volumes on
      planning CT and diagnostic CT. The mean time interval between end of chemotherapy
      and day of diagnostic CT was 16 days, and till first day of radiotherapy 80.3
      (range 29-141) days. In all, 41% of potentially curable patients became incurable
      in the waiting period. The ratio of gross tumour volumes of the two CTs ranged
      from 1.1 to 81.8 and the tumour doubling times ranged from 8.3 to 171 days, with
      a mean value of 46 days and median value of 29 days. This is far less than the
      mean doubling time of NSCLC in untreated patients found in the literature. This
      study shows that in the time interval between the end of induction chemotherapy
      and the start of radiotherapy rapid tumour progression occurs as a result of
      accelerated tumour cell proliferation: mean tumour doubling times are much
      shorter than those in not treated tumours. As a consequence, the gain obtained
      with induction chemotherapy with regard to volume reduction was lost in the
      waiting time for radiotherapy. We recommend diminishing the time interval between
      chemo- and radiotherapy to as short as possible.

PMID- 14676793
TI  - Domiciliary chemotherapy with gemcitabine is safe and acceptable to advanced non
      small-cell lung cancer patients: results of a feasibility study.
AB  - A study was conducted to investigate the feasibility and acceptability of
      administering single-agent gemcitabine to patients with advanced non-small-cell
      lung cancer (NSCLC) in their own homes. Gemcitabine is an active agent in NSCLC
      with a good toxicity profile and lends itself to this type of investigation. A
      total of 24 patients were studied; as only one patient required gemcitabine to be
      changed from home administration to hospital administration, domiciliary
      gemcitabine is feasible. A total of 249 injections of gemcitabine were given, the
      mean number of courses being 3.5, range 1-6. The gemcitabine was given at 1000 mg
      m(-2) on days 1, 8 and 15, the courses being repeated every 28 days. All patients
      received their first course in hospital and in total 147 were given at home and
      only 14 in hospital on courses 2-6. Furthermore, both the patients and carers
      reported positively on the use of domiciliary gemcitabine and preferred it over
      hospital administration. There was no evidence of increasing burden to community
      services during the domiciliary chemotherapy. Further studies investigating this
      approach are warranted.

PMID- 14676794
TI  - Low-risk persistent gestational trophoblastic disease treated with low-dose
      methotrexate: efficacy, acute and long-term effects.
AB  - The aim of this study was to evaluate the efficacy and toxicity of low-dose
      methotrexate with folinic acid rescue in a large series of consecutively treated
      patients with low-risk persistent gestational trophoblastic disease. Between
      January 1987 and December 2000, 250 patients were treated with intramuscular
      methotrexate (50 mg on alternate days 1, 3, 5, 7) with folinic acid (7.5 mg
      orally on alternate days 2, 4, 6, 8) rescue. The overall complete response rate
      without recurrence was 72% for first-line treatment and 95% for those who
      required second-line chemotherapy. Eight women (3.2%) had recurrence following
      remission and two (0.8%) had new moles. Two women (0.8%) died of their disease
      giving an overall cure of 99%. Only 10 women (4%) experienced grade III/IV
      toxicity during the first course of treatment and 13 women (5.2%) subsequently.
      Toxicity included mucositis and stomatitis, pleuritic chest pain,
      thrombocytopenia, uterine bleeding, abdominal pain, liver function changes, rash
      and pericardial effusion. A total of 59 women (23.6%) required second-line
      chemotherapy; 48 women had methotrexate resistance, eight had methotrexate
      toxicity and an empirical decision to change therapy was made in three. In all,
      11 women (4.4%) had a hysterectomy before, during or after treatment; 141 women
      (56.4%) became pregnant following treatment: in 128 (90.7%), the outcome was
      successful. Methotrexate with folinic acid rescue is an effective treatment for
      low-risk persistent trophoblastic disease. It has minimal severe toxicity,
      excellent cure rates and does not appear to affect fertility.

PMID- 14676795
TI  - Subjective quality of life and sexual functioning after germ-cell tumour therapy.
AB  - PURPOSE: To evaluate the influence of germ-cell tumour therapy on sexual
      functioning and subjective quality of life (QL). To investigate the communication
      about sexual problems between patients, their partners, and doctors. In all, 474
      patients treated for germ-cell tumours at the Department of Internal Medicine
      III, Ludwig-Maximilians-University Munich, from 1979 to 2000 were asked to
      complete a self-report questionnaire concerning psychosocial dimensions and
      subjective QL (QLS; Henrich and Herschbach, 2000). In total, 341 patients
      returned a completed questionnaire (response rate, 71.9%). The median age at
      survey was 41.9 years and the median follow-up period after therapy was 9.6
      years. Persisting sexual sequelae were lower than in the current literature:
      decreased sexual desire (7.1%), erection (10.0%), orgasm (10.2%), ejaculation
      (28.8%), sexual activity (8.5%), and sexual satisfaction (4.8%). In QL the
      satisfaction with 'friends/acquaintances' (P<0.001) and 'family life/children'
      (P<0.001), is lower than in the healthy population. Correlations between
      functional scales and subjective QL were highly significant. There is a strong
      correlation between sexual satisfaction and global life satisfaction (Spearman's
      Rho: 0.48; P<0.01). A total of 61.4% of patients were not offered communication
      about sexual problems by their doctors and 21.2% were unable to talk with their
      partner about sexual issues. In conclusion, moderating psychosocial variables
      (e.g. personality factors, cognitive processes) should be investigated to clarify
      the relationship between life satisfaction (subjective QL) and functional
      impairments. Communication about sexual problems should be offered as a standard
      to patients treated for germ-cell tumours.

PMID- 14676796
TI  - Phase I/II study of S-1 combined with cisplatin in patients with advanced gastric
      cancer.
AB  - A dose-escalation study of cisplatin (CDDP) combined with S-1, a new oral
      dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to
      determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting
      toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer
      (AGC). S-1 was given orally at 40 mg m(-2) b.i.d. for 21 consecutive days
      following a 2-week rest. CDDP was planned to be given intravenously on day 8, at
      a dose of 60, 70, or 80 mg m(-2) depending on the DLT. Treatment was repeated
      every 5 weeks, unless disease progression was observed. In the phase I portion,
      the MTD of CDDP was presumed to be 70 mg m(-2), because 33.3% of patients (2/6)
      developed DLTs, mainly neutropenia. Therefore, the RD of CDDP was estimated as 60
      mg m(-2). In the phase II portion, 19 patients including six patients of the RD
      phase I portion were evaluated. The median administered courses was four (range:
      1-8). The incidences of severe (grades 3-4) haematological and nonhaematological
      toxicities were 15.8 and 26.3%, respectively, but all were manageable. The RR was
      74% (14/19, 95% confidence interval: 54.9-90.6%), and the median survival day was
      383. This regimen is considered to be active against AGC with acceptable
      toxicity.

PMID- 14676797
TI  - Subcutaneous interleukin-2, interferon alpha-2b and 5-fluorouracil in metastatic
      renal cell carcinoma as second-line treatment after failure of previous
      immunotherapy: a phase II trial.
AB  - The association of interleukin-2 (IL-2), interferon alpha-2a (IFNalpha), 5
      fluorouracil (5-FU) has been reported to induce response in metastatic renal cell
      carcinoma (MRCC). This study evaluated IL-2, IFNalpha and 5FU as second-line
      treatment after failure under immunotherapy. A total of 35 patients received IL
      2, at 9 x 10(6) IU m(-2), once or t.i.d, 5 days a week, every other week.
      Interferon alpha was administered at 6 MUI, TIW along with IL-2 every week. 5
      Fluorouracil was given at 750 mg m(-2) day(-1) on days 1-5 every 4 weeks. One
      cycle lasted 8 weeks. All patients were evaluable for response and toxicity.
      There were two objective responses (5.7%) and 14 stable diseases (40%). Survival
      was 14 months. In all, 17 patients experienced grade 3 toxicity. The predictive
      factor for progression to second-line immunotherapy was the results of first-line
      immunotherapy, and performance status, delay from primary tumour to metastases
      and response or stabilisation to chemo-immunotherapy for survival. IL-2, IFNalpha
      and 5-FU induce low objective response but stabilisation in patients with MRCC
      having failed with immunotherapy, and may be considered only in selected patients
      on performance status, stabilisation or response after first-line immunotherapy
      and interval from their primary tumour to metastases.

PMID- 14676798
TI  - Palliative chemotherapy or best supportive care? A prospective study explaining
      patients' treatment preference and choice.
AB  - In palliative cancer treatment, the choice between palliative chemotherapy and
      best supportive care may be difficult. In the decision-making process, giving
      information as well as patients' values and preferences become important issues.
      Patients, however, may have a treatment preference before they even meet their
      medical oncologist. An insight into the patient's decision-making process can
      support clinicians having to inform their patients. Patients (n=207) with
      metastatic cancer, aged 18 years or older, able to speak Dutch, for whom
      palliative chemotherapy was a treatment option, were eligible for the study. We
      assessed the following before they consulted their medical oncologist: (1) socio
      demographic characteristics, (2) disease-related variables, (3) quality-of-life
      indices, (4) attitudes and (5) preferences for treatment, information and
      participation in decision-making. The actual treatment decision, assessed after
      it had been made, was the main study outcome. Of 207 eligible patients, 140
      patients (68%) participated in the study. At baseline, 68% preferred to undergo
      chemotherapy rather than wait watchfully. Eventually, 78% chose chemotherapy.
      Treatment preference (odds ratio (OR)=10.3, confidence interval (CI) 2.8-38.0)
      and a deferring style of decision-making (OR=4.9, CI 1.4-17.2) best predicted the
      actual treatment choice. Treatment preference (total explained variance=38.2%)
      was predicted, in turn, by patients' striving for length of life (29.5%), less
      striving for quality of life (6.1%) and experienced control over the cause of
      disease (2.6%). Patients' actual treatment choice was most strongly predicted by
      their preconsultation treatment preference. Since treatment preference is
      positively explained by striving for length of life, and negatively by striving
      for quality of life, it is questionable whether the purpose of palliative
      treatment is made clear. This, paradoxically, emphasises the need for further
      attention to the process of information giving and shared decision-making.

PMID- 14676799
TI  - A randomised clinical trial of high-intensity focused ultrasound ablation for the
      treatment of patients with localised breast cancer.
AB  - High-intensity focused ultrasound (HIFU) is a noninvasive treatment that induces
      complete coagulative necrosis of a tumour at depth through the intact skin. This
      study was to explore the possibility of using HIFU for the treatment of patients
      with localised breast cancer in a controlled clinical trial. A total of 48 women
      with biopsy-proven breast cancer (T(1-2), N(0-2), M0) were randomised to the
      control group in which modified radical mastectomy was performed, and the HIFU
      group in which an extracorporeal HIFU ablation of breast cancer was followed by
      modified radical mastectomy. Short-term follow-up, pathologic and
      immunohistochemical stains were performed to assess the therapeutic effects on
      tumour and complications of HIFU. The results showed that no severe side effect
      was observed in the HIFU-treated patients. Pathologic findings revealed that HIFU
      treated tumour cells underwent complete coagulative necrosis, and tumour vascular
      vessels were severely damaged. Immunohistochemical staining showed that no
      expression of PCNA, MMP-9, and CD44v6 was detected within the treated tumour
      cells in the HIFU group, indicating that the treated tumour cells lost the
      abilities of proliferation, invasion, and metastasis. It is concluded that, as a
      noninvasive therapy, HIFU could be effective, safe, and feasible in the
      extracorporeal treatment of localised breast cancer.

PMID- 14676800
TI  - Phase I clinical trial of the bispecific antibody MDX-H210 (anti-FcgammaRI x anti
      HER-2/neu) in combination with Filgrastim (G-CSF) for treatment of advanced
      breast cancer.
AB  - A phase I study of the bispecific antibody MDX-H210 in combination with
      granulocyte colony-stimulating factor (G-CSF) was performed in stage IV breast
      carcinoma patients, overexpressing HER-2/neu. MDX-H210, constructed by
      crosslinking antigen binding fragments (F(ab') fragments) of monoclonal antibody
      (mAb) H22 to Fc gamma receptor I (FcgammaRI), and mAb 520C9 to HER-2/neu,
      respectively, mediates the lysis of tumour cells in vitro, and in human FcgammaRI
      transgenic mouse models. The proto-oncogene HER-2/neu is overexpressed in
      approximately 30% of breast cancer patients, and represents a promising target
      for antibody-based immunotherapy. Fc gamma receptor I (CD64) is an effective
      trigger molecule, which is expressed on monocytes/macrophages, immature dendritic
      cells, and G-CSF-primed polymorphonuclear cells (PMN). Patients received G-CSF
      (Filgrastim) for 8 consecutive days, and cohorts of three patients were treated
      on day 4 with escalating, single doses of MDX-H210. A total of 30 patients were
      included, and treatment was generally well tolerated, without reaching dose
      limiting toxicity. Side effects consisted mainly of fever and short periods of
      chills, which were timely related to elevated plasma levels of interleukin 6 and
      tumour necrosis factor alpha. In the last two cohorts, MDX-H210 plasma levels
      exceeded 1 microg ml(-1), and on circulating myeloid cells >50% saturation of
      FcgammaRI was found until day 4. These effector cells were highly effective in
      antibody-dependent cell-mediated cytotoxicity. Immunohistochemical analyses of
      tumour biopsies in individual patients documented infiltration of monocytes and
      PMN after MDX-H210 infusion. Although the clinical course of the disease was not
      altered by the single dose of MDX-H210, a favourable toxicity profile--even at
      high doses--and remarkable biological effects were seen when combined with G-CSF.
      Therefore, the combination of G-CSF and MDX-H210 should be evaluated in further
      immunotherapeutical strategies.

PMID- 14676801
TI  - Survivin expression in oral squamous cell carcinoma.
AB  - A series of 110 cases of oral squamous cell carcinoma (SCC) together with six
      lymph node and one distant metastatic lesions was analysed for expression of
      survivin, a recent apoptosis inhibitor, by immunohistochemistry and Western
      blotting. In total, 91 cases (82.7%) of carcinoma and all metastasis (seven
      cases, 100%) were positive for survivin expression, with weighted survivin scores
      ranging from 1 to 4. In contrast, normal oral epithelium did not express
      survivin. There was no significant correlation between survivin expression and
      age, sex, tumour size, the presence of lymph node and distant metastases.
      Survivin expression was increased in poorly differentiated tumours, even if
      differences were not statistically significant. In contrast, when analysed for
      prognostic significance, patients with low survivin expression had statistically
      significant better survival rates than the group with high survivin expression
      (P<0.05). These data suggest that survivin expression may identify cases of oral
      SCC with more aggressive and invasive phenotype.

PMID- 14676802
TI  - TP53 mutations in vulval lichen sclerosus adjacent to squamous cell carcinoma of
      the vulva.
AB  - Non-neoplastic epithelial lesions of the vulva (NNEDV) lichen sclerosus (LS) and
      squamous hyperplasia (SH) have been implicated in the pathogenesis of squamous
      cell carcinoma of the vulva (SCC). To date, there have been no recognisable
      precursor lesions for SCC associated with NNEDV. TP53 is the most frequent
      genetic change in human cancers and can indicate both aetiology and molecular
      pathogenesis of tumours. A total of 27 SCC patients underwent
      immunohistochemistry (IHC) and TP53 mutational analysis using microdissection and
      direct sequencing. There were 19 patients with areas of adjacent epidermis: 17
      had NNEDV (four SCCs had more than one adjacent lesion) and two had normal
      epidermis. In all, 70.4% of the SCCs, 40% LS and 22.2% SH demonstrated
      overexpression of p53. In total, 77.8% of SCCs, 46.7% of LS and 22.2% SH
      demonstrated mutations in TP53, with the majority of lesions having a mutation in
      codon 136. Eight cases were identified where the same mutation was identified in
      the SCC and in the adjacent area. These data suggest that TP53 mutations develop
      in NNEDV and are intrinsic to the clonal evolution that leads to SCC. The type of
      mutation detected is more likely to occur due to endogenous cellular changes
      rather than exogenous carcinogen exposure.

PMID- 14676803
TI  - The embedded tumour: host physiology is important for the evaluation of tumour
      growth.
AB  - The growth potential of a tumour can significantly depend on host features such
      as age, cell proliferation rates and caloric intake. Although this is widely
      known, existing mathematical models for tumour growth do not account for it. We
      therefore developed a new model for tumour growth, starting from a mathematical
      framework that describes the host's physiology. The resulting tumour-in-host
      model allowed us to study the implications of various specific interactions
      between the energetics of tumour and host. The model accounts for the influence
      of both age and feeding regimen of the host organism on the behaviour of a
      tumour. Concerning the effects of a tumour on its host, it explains why tumour
      mediated body-weight loss is often more dramatic than expected from the energy
      demands of the tumour. We also show how the model can be applied to study
      enhanced body-weight loss in presence of cachectic factors. Our tumour-in-host
      model thus appears a proper tool to unite a wide range of phenomena in tumour
      host interactions.

PMID- 14676804
TI  - Potential use of the alkaline comet assay as a predictor of bladder tumour
      response to radiation.
AB  - Bladder tumours show a variable response to radiotherapy with only about 50%
      showing good local control; currently there is no test to predict outcome prior
      to treatment. We have used five bladder tumour cell lines (T24, UM-UC-3, TCC-SUP,
      RT112, HT1376) to investigate the potential of the alkaline comet assay (ACA) to
      predict radiosensitivity. Radiation-induced DNA damage and repair were compared
      to clonogenic survival. When the five cell lines were irradiated and initial DNA
      damage was plotted against cell survival, at all doses (0-6 Gy), a significant
      correlation was found (r2=0.9514). Following 4 Gy X-irradiation, all cell lines,
      except T24, showed a correlation between SF2 vs half-time for repair and SF2 vs
      residual damage at 5, 10, 20 and 30 min. The T24 cell line showed radioresistance
      at low doses (0-2 Gy) and radiosensitivity at higher doses (4-6 Gy) using both
      cell survival and ACA end points, explaining the lack of correlation observed for
      this cell line. These data indicate that initial DNA damage and residual damage
      can be used to predict for radiosensitivity. Our data suggest that predictive
      tests of radiosensitivity, appropriate to the clinical situation, may require the
      use of test doses in the clinical range.

PMID- 14676805
TI  - Measurements using the alkaline comet assay predict bladder cancer cell
      radiosensitivity.
AB  - In the UK, the two main treatments of invasive bladder cancer are radiotherapy or
      cystectomy. However, approximately 50% of patients undergoing radiotherapy fail
      to respond. If tumour radiosensitivity could be predicted in advance, it may be
      possible to improve control rates significantly by selecting for radiotherapy
      those patients whose tumours are radiosensitive. Additionally, patients who would
      benefit from surgery would be identified earlier. The alkaline comet assay (ACA)
      is a sensitive method for the detection of DNA strand break damage in cells. In
      the present study, using six bladder cancer cell lines of differing
      radiosensitivities, cell survival was compared to the manifestation of radiogenic
      DNA damage as assessed by ACA. For all the cell lines, the extent of comet
      formation strongly correlates with cell killing (R2>0.96), with a greater
      response being noted in radiosensitive cells. In repair studies, measures of
      residual damage correlate with survival fraction at 2 Gy (R2>0.96), but for only
      five of the cell lines. Finally, cells from human bladder tumour biopsies reveal
      a wide range of predicted radiosensitivies as determined by ACA. Overall, these
      studies demonstrate ACA to be a good predictive measure of bladder cancer cell
      radiosensitivity at low dose, with potential clinical application.

PMID- 14676806
TI  - Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and
      DNA damage/repair in human colon cancer cells.
AB  - The intrinsic radiation sensitivity of normal and tumour tissue is a major
      determinant of the outcome of radiotherapy. There is currently no established
      test that can be used routinely to measure the radiosensitivity of the cells in
      an individual patient's cancer in a manner that can inform treatment planning.
      The purpose of this study was to evaluate, in four human colorectal
      adenocarcinoma cell lines, two possible end points as surrogate markers of
      radiation response--apoptosis and induction of DNA single-strand breaks--and to
      compare the results with those of a conventional clonogenic assay. Cell lines
      (SW707 SW480, SW48 and HT29) known to differ in radiosensitivity were exposed to
      single doses of X-rays ranging from 0.5 to 5 Gy and cell survival was measured
      using the clonogenic assay. Apoptosis was determined on the basis of morphology
      under fluorescent microscopy and DNA damage/repair was measured, as tail moment,
      using an adaptation of the alkaline comet assay. The relationship between
      surviving fraction at 2 Gy (SF2) and the percentage of apoptotic cells 24 h after
      the same dose was complex, but apoptosis accurately predicted the order of
      radiosensitivities as measured by SF2. Initial damage measured after 2 Gy using
      the alkaline comet assay gave a close correlation with SF2 (r2=0.95), whereas
      there was no correlation between initial DNA damage repair rate and SF2.

PMID- 14676807
TI  - Gene expression array profile of human osteosarcoma.
AB  - The aims of this pilot study were to determine whether needle and open biopsies
      from osteosarcoma (OS) provide sufficient quality of mRNA for cDNA array analyses
      to gain insights into the expression profile of OS. A total of 22 samples
      collected from OS were used for array analyses. A primary cell culture was also
      established from one of the OS biopsies. Total RNA was extracted and probes were
      generated for cDNA arrays. cDNA probes were made for all the 22 samples. Two of
      these samples were needle core bone biopsies. Statistical analysis confirmed the
      reliability of array data obtained in 16 of the 22 samples. Known genes involved
      in bone metabolism and osteosarcoma were identified as highly expressed, and the
      putative new marker Ezrin was also identified. Confirmatory immunohistochemical
      staining using the Ezrin antibody was performed in a selection of samples.

PMID- 14676808
TI  - Allelotype of 28 human breast cancer cell lines and xenografts.
AB  - Heterozygous loss of relatively large chromosomal regions is a hallmark of the
      inactivation of tumour suppressor genes. Searching for deletions in cancer
      genomes therefore provides an attractive option to identify new tumour suppressor
      genes. Here, we have performed a genome-wide survey for regions exhibiting
      allelic loss in 24 commercially available breast cancer cell lines and four
      breast cancer xenografts, using microsatellite analysis. The assembled allelotype
      revealed an average fractional allelic loss of 0.34. A total of 19 arms had low
      allelic loss frequencies (<25%) and 17 arms had moderate allelic loss frequencies
      (25-50%). Five chromosomal arms were deleted in more than half of the breast
      cancer samples (8p, 10q, 13q, 17p, and 17q). Three of these frequently lost
      chromosomal arms had not been identified as such by comparative genome
      hybridisation, illustrating the higher sensitivity of microsatellite analysis for
      the detection of allelic losses. As we present allelic loss data of individual
      samples, our allelotype should not only aid the identification of new breast
      cancer genes but also provides a baseline for myriad studies involving these
      breast cancer cell lines.

PMID- 14676809
TI  - C-erbB-2 or mutant Ha-ras induced malignant transformation of immortalized human
      ovarian surface epithelial cells in vitro.
AB  - Ovarian cancer is believed to develop from the ovarian surface epithelium through
      the accumulation of aberrations of oncogenes and/or tumor suppressor genes.
      However, it is unclear how the gene abnormalities are involved in ovarian
      carcinogenesis. To elucidate the process, we transfected genes reported to show
      their abnormalities in human ovarian cancers into human ovarian surface
      epithelial cells. Immortalization of the cells was achieved by the transfection
      of SV40 large T antigen (LT) and human telomerase reverse transcriptase (hTERT);
      however, the resultant cells showed no tumorigenesis. Additional transfection of
      either c-erbB-2 or mutant Ha-ras into the immortalized cells showed the anchorage
      independent growth and tumorigenesis in mice with the incidence of 50% and 40%,
      respectively. Histologically, all the tumours were undifferentiated. In
      association with the tumorigenesis, the cells expressing c-erbB-2 or mutant Ha
      ras demonstrated increased vascular endothelial growth factor secretion under
      hypoxia and enhanced resistance to apoptosis compared with the immortalized
      cells. Collectively, the introduction of either c-erbB-2 or mutant Ha-ras in the
      cells, which were efficiently immortalized by the transfection of LT and hTERT,
      showed tumorigenicity, suggesting that c-erbB-2 or mutant Ha-ras genes might be
      involved in ovarian carcinogenesis.

PMID- 14676810
TI  - Combination chemotherapy in advanced gastrointestinal cancers: ex vivo
      sensitivity to gemcitabine and mitomycin C.
AB  - Advanced or metastatic disease is common in both oesophagogastric and colorectal
      cancers, with poor 5-year survival despite palliative chemotherapy. We have
      investigated the sensitivity of gastrointestinal tumours to gemcitabine in
      combination with mitomycin C (GeM), using a modified ex vivo ATP-based tumour
      chemosensitivity assay (ATP-TCA). Tumour material from 41 colorectal and 22
      oesophagogastric cancers were assessed. The GeM combination showed variable but
      definite activity in most of the samples tested. The results show that GeM
      achieves >95% inhibition at concentrations within the range achievable clinically
      in 60% of colorectal tumours (21 out of 35) and 38% of oesophagogastric tumours
      (five out of 13) tested. We did not identify any significant difference in
      sensitivity using concurrent or sequential exposure of tumour-derived cells to
      these two drugs. The results from this study suggest that GeM may be a useful
      combination in the treatment of advanced gastrointestinal malignancy.

PMID- 14676811
TI  - In vitro interaction between ecteinascidin 743 (ET-743) and radiation, in
      relation to its cell cycle effects.
AB  - Ecteinascidin 743 (ET-743) is a new marine-derived agent with promising activity
      against a number of solid tumours. In four human tumour cell lines, the
      interaction between ET-743 and radiation was investigated in relation to the
      effects of ET-743 on the cell cycle, in vitro. Cell survival was measured based
      on quantitative staining of cellular protein by sulforhodamine B. A 24 h
      treatment with ET-743 before radiation resulted in a moderate increase in
      radiosensitivity in three out of four cell lines. Dose enhancement factors > or
      =1.8 were observed for concentrations resulting in 52, 46 and 30% cell kill in
      ECV304, H292 and CAL-27, respectively, whereas in A549 no radiosensitisation was
      observed (no significant increase in radiosensitivity). According to the
      combination index analysis, synergism was observed only in ECV304 and CAL-27
      cells. A 24 h incubation with ET-743 resulted in a concentration-dependent G2/M
      block, which might explain the moderate radiosensitising effects in ECV304 and
      H292. The lack of radiosensitisation in A549 might be due to the S phase delay
      preceding the G2/M block at the moment of radiation, which only occurred in this
      cell line. In conclusion, ET-743 has moderate cell line-dependent
      radiosensitising properties; however, only when cytotoxic concentrations of ET
      743 are used. In one of the four cell lines tested, no radiosensitisation was
      observed.

PMID- 14676812
TI  - Polarisation of a T-helper cell immune response by activation of dendritic cells
      with CpG-containing oligonucleotides: a potential therapeutic regime for bladder
      cancer immunotherapy.
AB  - Intravesical bacillus Calmette-Guerin (BCG) is a treatment for transitional cell
      carcinoma (TCC) and carcinoma in situ (cis) of the urinary bladder, but some
      patients remain refractory. The mechanism of cancer clearance is not known, but T
      cells are thought to play a contributory role. Tissue dendritic cells (DCs) are
      known to initiate antigen-specific immune responses following activation of
      receptors, which recognise molecular patterns on the surface of microorganisms. A
      family of these receptors, the toll-like receptors (TLRs), are also crucial for
      activating DC to produce cytokines that polarise the T-cell response towards a T
      helper (Th)1 or Th2 phenotype. This study compared the potential of intact BCG to
      activate DC with that of the defined TLR4 ligand lipopolysaccharide (LPS) and the
      TLR9 ligand CpG-oligonucleotide. It was found that all three stimuli efficiently
      activated normal DC, but cells expressing a mutant TLR4 responded poorly to
      stimulation with LPS. Importantly, stimulation with BCG induced both IL-12 and IL
      10, suggesting subsequent development of a poorly focused T-cell immune response
      containing both Th1 and Th2 immune function. By contrast, LPS- and CpG
      oligonucleotides induced only IL-12, indicating the potential to produce a Th1
      response, which is likely to clear cancer most efficiently. Given the toxicity of
      LPS, our data suggest that CpG-oligonucleotides may be beneficial for
      intravesical therapy of bladder cancer.

PMID- 14676813
TI  - Selectivity of the photosensitiser Tookad for photodynamic therapy evaluated in
      the Syrian golden hamster cheek pouch tumour model.
AB  - The response to photodynamic therapy (PDT) with the photosensitiser (PS) Tookad
      was measured in the Syrian hamster cheek pouch model on normal mucosae and
      chemically induced squamous cell carcinoma. This PS is a palladium
      bacteriopheophorbide presenting absorption peaks at 538 and 762 nm. The light
      dose, drug dose and drug injection-light irradiation times (DLI), ranging between
      100 and 300 J cm(-2), 1-5 mg kg(-1) and 10-240 min respectively, were varied and
      the response to PDT was analysed by staging the macroscopic response and by the
      histological examination of the sections of the irradiated cheek pouch. A fast
      time decay of the tissular response with drug dose of 1-5 mg kg(-1) was observed
      for DLI ranging from 10 to 240 min and for light doses of 100-300 J cm(-2)
      delivered at a light dose rate of 150 mW cm(-2). A significantly higher level of
      tissular response was observed for squamous cell carcinoma compared to normal
      tissue. Nevertheless, the threshold level of the drug-light dose for a detectable
      response was not significantly different in the tumoral vs normal tissue. The
      highest response at the shortest DLIs and the absence of measurable response at
      DLI larger than 240 min at light dose of 300 J cm(-2) and drug dose of 5 mg kg(
      1) reveals the predominantly vascular effect of Tookad. This observation suggests
      that Tookad could be effective in PDT of vascularised lesions.

PMID- 14676814
TI  - Correlation between genetic alterations and growth of human malignant glioma
      xenografted in nude mice.
AB  - In order to develop preclinical models of malignant astrocytomas and
      oligodendrogliomas, a series of 54 resected gliomas (37 from oligodendroglial
      lineage and 17 from astrocytic lineage) were xenografted subcutaneously into nude
      mice. Molecular alterations commonly observed in gliomas subtypes, including LOH
      1p and 1q, LOH 19q, LOH 10p and 10q, LOH 9p, TP53 and PTEN mutations, EGFR
      amplification, CDKN2A homozygous deletion and telomerase reactivation were
      systematically screened in the original and xenografted tumours. In all, 23
      gliomas grew in nude mice. The most anaplastic tumours were selected as shown by
      pathological and molecular studies of the original tumour as well as shorter
      survival in patients whose tumours were successfully grafted. Comparison between
      the two growth profiles showed that 10q LOH and EGFR amplification gave a
      tumorigenic advantage. With a few exceptions, the genetic pattern was remarkably
      stable before and after growth in nude mice. These results suggest that
      subcutaneous xenografts are useful and reproducible models to analyse the
      molecular profile of malignant astrocytoma and oligodendroglioma. This represents
      the first step to improve our understanding of the correlations between molecular
      alterations and response to standard or experimental therapies.

PMID- 14676815
TI  - Combined hyperthermia and chlorophyll-based photodynamic therapy: tumour growth
      and metabolic microenvironment.
AB  - The effects of combined and simultaneously applied localised 43 degrees C
      hyperthermia (HT) and an antivascular bacteriochlorophyll-serine-based
      photodynamic therapy (Bchl-ser-PDT) on tumour growth and several
      microenvironmental parameters were examined. Rats bearing DS-sarcomas were
      allocated to treatment groups: (i) sham-treatment (control), (ii) Bchl-ser-PDT
      (20 mg kg(-1) i.v.), (iii) localised HT, (iv) Bchl-ser-PDT+HT. The light source
      used was an infrared-A irradiator, which, by use of appropriate filters,
      delivered the different ranges of wavelengths required. Following treatment,
      tumour volume was monitored. The greatest tumour growth inhibition was seen with
      Bchl-ser-PDT+HT, and subsequent experiments identified the pathophysiological
      basis for this effect. Red blood cell flux in tumour microvessels declined
      rapidly upon Bchl-ser-PDT+HT, reaching approximately 10% of initial values by the
      end of treatment. Similarly, tumour oxygenation worsened, reaching almost anoxic
      levels by the end of the treatment period. Assessment of metabolic parameters
      showed a pronounced increase in lactate levels and a decrease in ATP
      concentrations after combined treatment. The results presented suggest that
      vascular collapse and flow stasis resulting in a deterioration of tumour
      oxygenation and a switch from oxidative to glycolytic glucose turnover are key
      elements in the tumour eradication seen with this novel approach in which an
      antivascular PDT and HT are combined and simultaneously applied.

PMID- 14676816
TI  - Integrin-linked kinase (ILK) expression in human colon cancer.

PMID- 14676821
TI  - Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors.
AB  - The required dose of the oral anticoagulant warfarin varies greatly, and
      overdosing often leads to bleeding. Warfarin is metabolised by cytochrome P450
      enzymes CYP2C9, CYP1A2 and CYP3A. The target cell level of warfarin may be
      dependent on the efflux pump P-glycoprotein, encoded by the adenosine
      triphosphate-binding cassette gene ABCB1 (multidrug resistance gene 1). Genetic
      variability in CYP2C9, CYP3A5 and ABCB1 was analysed in 201 stable warfarin
      treated patients using solid-phase minisequencing, pyrosequencing and SNaPshot.
      CYP2C9 variants, age, weight, concurrent drug treatment and indication for
      treatment significantly influenced warfarin dosing in these patients, explaining
      29% of the variation in dose. CYP3A5 did not affect warfarin dosing. An ABCB1
      haplotype containing the exon 26 3435T variant was over-represented among low
      dose patients. Thirty-six patients with serious bleeding complications had higher
      prothrombin time international normalised ratios than 189 warfarin-treated
      patients without serious bleeding, but there were no significant differences in
      CYP2C9, CYP3A5 or ABCB1 genotypes and allelic variants.

PMID- 14676822
TI  - Human cytosolic sulfotransferase database mining: identification of seven novel
      genes and pseudogenes.
AB  - A total of 10 SULT genes are presently known to be expressed in human tissues. We
      performed a comprehensive genome-wide search for novel SULT genes using two
      different but complementary approaches, and developed a novel graphical display
      to aid in the annotation of the hits. Seven novel human SULT genes were
      identified, five of which were predicted to be pseudogenes, including two
      processed pseudogenes and three pseudogenes that contained introns. Those five
      pseudogenes represent the first unambiguous SULT pseudogenes described in any
      species. Expression-profiling studies were conducted for one novel gene, SULT6B1,
      and a series of alternatively spliced transcripts were identified in the human
      testis. SULT6B1 was also present in chimpanzee and gorilla, differing at only
      seven encoded amino-acid residues among the three species. The results of these
      database mining studies will aid in studies of the regulation of these SULT
      genes, provide insights into the evolution of this gene family in humans, and
      serve as a starting point for comparative genomic studies of SULT genes.

PMID- 14676823
TI  - The HapMap project and its application to genetic studies of drug response.

PMID- 14676824
TI  - Overexpression of LRP12, a gene contained within an 8q22 amplicon identified by
      high-resolution array CGH analysis of oral squamous cell carcinomas.
AB  - Chromosome 8q amplification is a common event observed in cancer. In this study,
      we used high-resolution array comparative genomic hybridization to resolve two
      neighboring regions on 8q that are both amplified in oral cancer. One region (at
      8q24) contains the MYC oncogene, which is frequently overexpressed in many
      cancers, while the other region (at 8q22) represents a novel amplicon. The
      alignment of array comparative genomic hybridization profiles of 20
      microdissected oral squamous cell carcinomas (OSCCs) revealed a approximately 5
      Mbp region of frequent copy number alteration. This region harbors 16 known
      genes. Gene expression analysis comparing 15 microdissected OSCC with 16 normal
      epithelium samples revealed overexpression specific to LRP12 but not the
      neighboring genes, dihydropyrimidinase and FOG2, suggesting that LRP12 may
      function as an oncogene in oral tumors.

PMID- 14676825
TI  - Mechanism of processing of the NF-kappa B2 p100 precursor: identification of the
      specific polyubiquitin chain-anchoring lysine residue and analysis of the role of
      NEDD8-modification on the SCF(beta-TrCP) ubiquitin ligase.
AB  - Processing of the NF-kappa B2 precursor p100 to the mature p52 subunit is
      regulated via a unique pathway. NF-kappa B-inducing kinase (NIK) induces I kappa
      B kinase alpha (IKK alpha)-mediated phosphorylation of specific serine residues
      in the C-terminal domain of p100, leading to recruitment of the SCF(beta-TrCP)
      ubiquitin ligase. We identified a single lysine residue, K855, that serves as the
      ubiquitin-anchoring residue required for signal-induced processing of p100. In a
      reconstituted system containing purified components, p100-K855R could not be
      ubiquitinated. In a crude extract and cells, only residual, signal-independent
      ubiquitination and processing were retained. Importantly, K855 is located in a
      site homologous to K22 that serves as an ubiquitination site in I kappa B alpha.
      This suggests a common recognition mechanism for the two molecules. In contrast,
      p105, the p100 homologue, lacks a similar Lys residue. We also demonstrate that
      the NEDD8 pathway is essential for the SCF(beta-TrCP) activity. In a
      reconstituted system, efficient ubiquitination of p100 required all three
      components of the pathway - E1, the UBC12 E2 and NEDD8. Experiments in
      reconstituted systems and in cells demonstrated that SCF(beta-TrCP), which
      contains a mutant Cul-1 that cannot be NEDDylated, cannot stimulate
      ubiquitination and processing. Similarly, dominant negative UBC12 inhibits, in a
      reversible manner, both ubiquitination and processing of p100.

PMID- 14676826
TI  - Role of Bim in the survival pathway induced by Raf in epithelial cells.
AB  - Selective and sustained activation of the Raf/MAP kinase pathway in MCF-10A Delta
      Raf-ER cells, a spontaneously immortalized human mammary epithelial cell line,
      was previously shown to protect these cells from suspension-induced cell death, a
      critical feature of the Ras-transformed phenotype. Although autocrine signalling
      through the EGF receptor is crucial for the protection induced by Raf in these
      cells, we report here the existence of an additional, more direct survival
      mechanism, linking Raf activation to the inhibition of a proapoptotic member of
      the Bcl-2 family, Bim. While detachment from the matrix results in
      transcriptional induction of two variants of this BH3-only protein, BimEL and
      BimL, activation of the Raf/ERK signalling both prevents Bim upregulation
      specifically and leads to phosphorylation and degradation of the BimEL isoform.
      This represents an important route to protect epithelial cells from the
      proapoptotic effect of Bim.

PMID- 14676827
TI  - Overexpression of leukocyte marker CD43 causes activation of the tumor suppressor
      proteins p53 and ARF.
AB  - CD43 or leukosialin is a transmembrane sialoglycoprotein, whose extracellular
      domain participates in cell adhesiveness and the cytoplasmic tail regulates a
      variety of intracellular signal transduction pathways involved in cell
      proliferation. CD43 is abundantly expressed on the surface of hematopoietic
      cells, but CD43 expression is also frequently found in the tumor cells of
      nonhematopoietic origin. In the early stages of some tumors, the accumulation of
      tumor suppressor protein p53 has been described. Here, we show that the
      expression of CD43 causes the induction of functionally active p53 protein.
      Moreover, we found that the activation of p53 by CD43 is mediated by tumor
      suppressor protein ARF. The coexpression of CD43 and ARF in ARF-null mouse
      embryonic fibroblasts resulted in programmed cell death, but that was not the
      case when CD43 alone was expressed in these cells. These data provide the first
      evidence of the connection between p53- and CD43-dependent pathways.

PMID- 14676828
TI  - Transcriptional regulation by the estrogen receptor of antioxidative stress
      enzymes and its functional implications.
AB  - We previously reported that antiestrogen-liganded estrogen receptor beta (ERbeta)
      transcriptionally activates the major detoxifying enzyme quinone reductase (QR)
      (NAD(P)H:quinone oxidoreductase). Our studies also indicate that upregulation of
      QR, either by overexpression or induction by tamoxifen, can protect breast cells
      against oxidative DNA damage caused by estrogen metabolites. We now report on the
      upregulation of glutathione S-transferases Pi (GST-Pi) and gamma-glutamylcysteine
      synthetase heavy subunit (GCSh) expression by antiestrogens. Studies indicate the
      regulation of GST-Pi and GCSh transcriptional activity by ER. While ER regulation
      is mediated by an electrophile response element (EpRE), we identified mechanistic
      differences in the involvement of other transcription factors. Regardless of
      these differences, ER beta-mediated regulation of GST-Pi and GCSh point towards
      an important role for ER beta in cellular protection against oxidative stress. A
      protective role is supported by our observation of inhibition of estrogen-induced
      DNA damage upon upregulation of GST-Pi and GCSh expression.

PMID- 14676829
TI  - Essential role of caspases in epigallocatechin-3-gallate-mediated inhibition of
      nuclear factor kappa B and induction of apoptosis.
AB  - Green tea constituent (-) epigallocatechin-3-gallate (EGCG) has shown remarkable
      cancer-preventive and some cancer-therapeutic effects. This is partially because
      of its ability to induce apoptosis in cancer cells without affecting normal
      cells. Previous studies from our laboratory have shown the involvement of NF
      kappa B pathway in EGCG-mediated cell-cycle deregulation and apoptosis of human
      epidermoid carcinoma A431 cells. Here we show the essential role of caspases in
      EGCG-mediated inhibition of NF-kappa B and its subsequent apoptosis. Treatment of
      A431 cells with EGCG (10-40 microg/ml) resulted in dose-dependent inhibition of
      NF-kappa B/p65, induction of DNA breaks, cleavage of poly(ADP-ribose) polymerase
      (PARP) and morphological changes consistent with apoptosis. EGCG treatment of
      cells also resulted in significant activation of caspases, as shown by the dose-
      and time-dependent increase in DEVDase activity, and protein expression of
      caspase-3, -8 and -9. EGCG-mediated caspase activation induces proteolytic
      cleavage of NF-kappa B/p65 subunit, leading to the loss of transactivation
      domains, and driving the cells towards apoptosis. EGCG-mediated induction of
      apoptosis was significantly blocked by the caspase inhibitor N-benzyloxycarbonyl
      Val-Ala-Asp(OMe)-fluoromethylketone (Z-VAD-FMK), and moderately blocked by the
      specific caspase-3 inhibitor Z-DEVD-FMK. Further, pretreatment of cells with Z
      VAD-FMK was found to suppress the cleavage of NF-kappa B/p65 subunit, thereby
      increasing nuclear translocation, DNA binding and transcriptional activity, thus
      protecting the cells from EGCG-induced apoptosis. Taken together, these studies
      for the first time demonstrate that EGCG-mediated activation of caspases is
      critical, at least in part, for inhibition of NF-kappa B and subsequent
      apoptosis.

PMID- 14676830
TI  - Identification of genes associated with tumorigenesis and metastatic potential of
      hypopharyngeal cancer by microarray analysis.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer
      among men in the developed world. There is a need, for both clinical and
      scientific reasons, to find markers to identify patients with aggressive disease
      as early as possible, and to understand the events leading to malignant
      transformation and susceptibility to metastasis. We report the first large-scale
      gene expression analysis of a unique HNSCC location, the hypopharynx. Four normal
      and 34 tumour samples were analysed with 12 600 gene microarrays. Clusters of
      differentially expressed genes were identified in the chromosomal regions 3q27.3,
      17q21.2-q21.31, 7q11.22-q22.1 and 11q13.1-q13.3, which, interestingly, have
      already been identified by comparative genomic hybridization (CGH) as major
      regions of gene amplification. We showed that six overexpressed genes (EIF4G1,
      DVL3, EPHB4, MCM7, BRMS1 and SART1) located in these regions are indeed
      amplified. We report 119 genes that are highly differentially expressed between
      'early' tumours and normal samples. Of these, we validated by quantitative PCR
      six novel poorly characterized genes. These genes are potential new markers of
      HNSCC. Comparing patients with relatively nonaggressive and aggressive tumours
      (without or with clinical evidence of metastasis 3 years after surgery), we
      identified 164 differentially expressed genes potentially involved in the
      acquisition of metastatic potential. This study contributes to the understanding
      of HNSCC, staging patients into prognostic groups and identifying high-risk
      patients who may benefit from more aggressive treatment.

PMID- 14676831
TI  - Inhibition of prostate tumor growth by overexpression of NudC, a microtubule
      motor-associated protein.
AB  - Microtubules play a central role in coordinating various cellular functions that
      are orchestrated by their interaction with molecular motors. Anticancer drugs
      that target microtubule dynamics have been shown to be effective in cancer
      treatment. However, the effect of microtubule motor-associated molecules on
      cancer cell proliferation is not clear. Here, we investigated the role of NudC, a
      nuclear movement protein associated with the microtubule motor dynein, on
      prostate tumorigenesis. Recombinant adenovirus expressing NudC (Ad-NudC) was used
      to examine the effects of NudC on the tumorigenicity of prostate cancer cells.
      Expression of NudC in LNCaP cells inhibited their anchorage-independent growth in
      a soft agar colony assay. Expression of NudC in DU145 or PC-3 cells inhibited
      tumor growth in a subcutaneous xenograft model. At the cellular level, expression
      of NudC in DU145 and PC-3 cells inhibited cell proliferation at 48 h after Ad
      NudC infection. FACS analysis of cell cycle distribution showed that 50-60% of Ad
      NudC-infected PC-3 cells have a G2/M-phase DNA content compared to about 16-19%
      in Ad-Luciferase (Ad-Luc)-infected control cells, suggesting that NudC
      overexpression resulted in aberrant cell cycle progression. Immunofluorescence
      microscopy revealed a significant increase in cells with a single enlarged
      nucleus and cells exhibiting multiple nuclei, along with a concomitant increase
      in cell size in Ad-NudC-infected cells. These results suggest that NudC
      overexpression led to a block in cell division of prostate cancer cells, and that
      Ad-NudC may provide a new anticancer drug approach targeting the function of a
      microtubule motor-associated protein.

PMID- 14676832
TI  - SV40-positive brain tumor in scientist with risk of laboratory exposure to the
      virus.
AB  - Simian virus 40 (SV40) is a DNA tumor virus known to induce cancers in laboratory
      animals. There are numerous reports of the detection of SV40 DNA and/or proteins
      in human malignancies of the same types as those induced by SV40 in animals,
      including brain cancers. However, known exposure to the virus has not yet been
      linked directly to cancer development in a specific individual. Here we describe
      the detection of SV40 sequences in the meningioma of a laboratory researcher who
      had a probable direct exposure to SV40 and subsequently developed a tumor
      positive for viral DNA sequences indistinguishable from those of the laboratory
      source. This case suggests a link between viral exposure and tumor development.

PMID- 14676833
TI  - Cystatin M suppresses the malignant phenotype of human MDA-MB-435S cells.
AB  - Proteases are involved in many aspects of tumor progression, including cell
      survival and proliferation, escape from immune surveillance, cell adhesion and
      migration, remodeling and invasion of the extracellular matrix. Several lysosomal
      cysteine proteases have been cloned and shown to be overexpressed in cancer; yet,
      despite the great potential for development of novel therapeutics, we still know
      little about the regulation of their proteolytic activity. Cystatins such as
      cystatin M are potent endogenous protein inhibitors of lysosomal cysteine
      proteases. Cystatin M is expressed in normal and premalignant human epithelial
      cells, but not in many cancer cell lines. Here, we examined the effects of
      cystatin M expression on malignant properties of human breast carcinoma MDA-MB
      435S cells. Cystatin M was found to significantly reduce in vitro: cell
      proliferation, migration, Matrigel invasion, and adhesion to endothelial cells.
      Reduction of cell proliferation and adhesion to an endothelial cell monolayer
      were both independent of the inhibition of lysosomal cysteine proteases. In
      contrast, cell migration and matrix invasion seemed to rely on lysosomal cysteine
      proteases, as both recombinant cystatin M and E64 were able to block these
      processes. This study provides the first evidence that cystatin M may play
      important roles in safeguarding against human breast cancer.

PMID- 14676834
TI  - Role of the Brk SH3 domain in substrate recognition.
AB  - Breast tumor kinase (Brk) is a nonreceptor tyrosine kinase that is overexpressed
      in a high percentage of breast carcinomas. Brk contains SH3, SH2, and tyrosine
      kinase catalytic domains in a similar arrangement as Src family kinases. In this
      study, we explored the roles of the SH3 and SH2 domains in Brk regulation and
      substrate binding. We introduced a series of mutations into Brk that were
      predicted to disrupt the intramolecular interactions involving the SH3 and SH2
      domains. These mutant forms of Brk displayed higher activity than wild-type Brk
      when expressed in human embryonic kidney HEK293 cells. These studies also allowed
      us to pinpoint the intramolecular binding site for the SH3 domain. To examine
      substrate binding, we compared binding and phosphorylation of Sam68, a
      physiological substrate of Brk. These experiments showed that the SH3 domain
      plays a particularly important role in substrate recognition. We confirmed this
      conclusion using a series of synthetic peptides in which a substrate sequence was
      coupled to an SH3 or SH2 ligand. The SH3-binding substrate had a significantly
      lower K(m) than a control, while no difference was observed between an SH2
      binding substrate and a control. Taken together, our data suggest that SH3
      interactions will govern phosphorylation of many substrates by Brk.

PMID- 14676835
TI  - Secretion of cytokines and growth factors as a general cause of constitutive
      NFkappaB activation in cancer.
AB  - The constitutive activation of nuclear factor kappaB (NFkappaB) helps a variety
      of tumors to resist apoptosis and desensitizes them to chemotherapy, but the
      causes are still largely unknown. We have analysed this phenomenon in eight
      mutant cell lines derived from human 293 cells, selected for NFkappaB-dependent
      expression of a marker gene, and also in seven tumor-derived cell lines.
      Conditioned media from all of these cells stimulated the activation of NFkappaB
      (up to 30-fold) in indicator cells carrying an NFkappaB-responsive reporter.
      Therefore, secretion of extracellular factors as the cause of constitutive
      activation seems to be general. The mRNAs encoding several different cytokines
      and growth factors were greatly overexpressed in the tumor and mutant cells. The
      pattern of overexpression was distinct in each cell line, indicating that the
      phenomenon is complex. Two secreted factors whose roles in the constitutive
      activation of NFkappaB are not well defined were investigated further as pure
      proteins: transforming growth factor beta2 (TGFbeta2) and fibroblast growth
      factor 5 (FGF5) were both highly expressed in some mutant clones and tumor cell
      lines, each activated NFkappaB alone, and the combination was synergistic. Our
      data indicate that a group of different factors, expressed at abnormally high
      levels, can contribute singly and synergistically to the constitutive activation
      of NFkappaB in all of the mutant and tumor cell lines we studied. Since several
      NFkappaB target genes encode secreted proteins that induce NFkappaB, autocrine
      loops are likely to be ubiquitously important in the constitutive activation of
      NFkappaB in cancer. We provide the first evidence of the general, complex, and
      synergistic activation of NFkappaB in tumor and mutant cell lines through the
      action of secreted factors and suggest that the same explanation is likely for
      the constitutive activation of NFkappaB in cancers.

PMID- 14676836
TI  - Androgens repress Bcl-2 expression via activation of the retinoblastoma (RB)
      protein in prostate cancer cells.
AB  - The oncogene Bcl-2 is upregulated frequently in prostate tumors following
      androgen ablation therapy, and Bcl-2 overexpression may contribute to the
      androgen-refractory relapse of the disease. However, the molecular mechanism
      underlying androgenic regulation of Bcl-2 in prostate cancer cells is understood
      poorly. In this study, we demonstrated that no androgen response element (ARE)
      was identified in the androgen-regulated region of the P1 promoter of Bcl-2 gene,
      whereas, we provided evidence that the androgenic effect is mediated by E2F1
      protein through a putative E2F-binding site in the promoter. We further
      demonstrated that retinoblastoma (RB) protein plays a critical role in androgen
      regulation of Bcl-2. The phosphorylation levels of RB at serine residues 780 and
      795 were decreased in LNCaP cells treated with androgens. Ectopic expression of a
      constitutively active form of RB inhibited expression of Bcl-2. Knockdown of
      endogenous RB protein by an Rb small inference RNA (siRNA) induced an increase in
      Bcl-2 levels. Most importantly, the effect of androgens on Bcl-2 was abolished
      completely by specific inhibition of RB function with a mutated E1A. Finally,
      androgen treatment of LNCaP cells upregulated specifically levels of the cyclin
      dependent kinase inhibitors (CDKIs) p15INK4B and p27KIP1. Ectopic expression of
      p15INK4B and/or p27KIP1 inhibited Bcl-2 expression. Knockdown of endogenous
      p15INK4B or p27KIP1 protein with a pool of siRNAs diminished androgen-induced
      downregulation of Bcl-2 expression. Therefore, our data indicate that androgens
      suppress Bcl-2 expression through negatively modulating activities of the E2F
      site in the Bcl-2 promoter by activating the CDKI-RB axis.

PMID- 14676837
TI  - The histone deacetylase inhibitor trichostatin A sensitizes estrogen receptor
      alpha-negative breast cancer cells to tamoxifen.
AB  - Many cases of breast cancer show loss of estrogen receptor (ER) alpha expression,
      which leads to unresponsiveness to antihormonal treatment even though there is no
      loss of the structurally and biochemically similar ER beta. ER activity is
      positively and negatively regulated by transcriptional regulators such as histone
      deacetylase (HDAC), which is known to be a negative ER regulator. Here, we
      evaluated using ER beta as an alternative target for tamoxifen therapy by
      treating ER alpha-negative, beta-positive breast cancer cells with the HDAC
      inhibitor trichostatin A (TSA), and testing whether tamoxifen responsiveness
      increased following upregulation of ER beta. TSA enhanced the overall ER
      transcriptional activity in these cells, as visualized by estrogen response
      element-regulated reporter and the expression of progesterone receptor, a known
      ER target, without ER alpha restoration. Additionally, TSA induced the expression
      and nuclear translocation of ER beta but not alpha, suggesting that these actions
      leading to increase of ER transcriptional activity are mediated through ER beta
      rather than alpha. Furthermore, following treatment with TSA, the formerly
      unresponsive MDA-MB-231 and Hs578T breast cancer cells became responsive to
      tamoxifen. However, reduction of ER beta expression by short interfering RNA
      abrogated this TSA-induced sensitization effect in these cells. Together, these
      results show that the HDAC inhibitor TSA sensitized ER alpha-negative,
      antihormone-unresponsive breast cancer cells to tamoxifen treatment possibly by
      upregulating ER beta activity.

PMID- 14676838
TI  - The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast
      cancer cells.
AB  - Etk/Bmx, a member of the Tec family of tyrosine kinases, mediates various
      signaling pathways and confers several cellular functions. In the present study,
      we have explored the functional role of Etk in mediating EGF-induced apoptosis,
      using MDA-MB-468 cell line as a model. We first demonstrated that EGF treatment
      induces Etk tyrosine phosphorylation in both HeLa and MDA-MB-468 cells.
      Overexpression of Etk by recombinant adenovirus in MDA-MB-468 cells potentiates
      the extent of EGF-induced cell apoptosis. The observed Etk-enhanced MDA-MB-468
      cell apoptosis is associated with the Stat1 activation, as demonstrated by
      electrophoresis mobility shift assays and reporter gene assays. By contrast, a
      kinase domain deletion mutant EtkDeltaK, functioning as a dominant-negative
      mutant, ameliorates EGF-induced Stat1 activation and apoptosis in MDA-MB-468
      cells. To explore whether the activated Etk alone is sufficient for inducing
      apoptosis, a conditionally activated Etk (DeltaEtk-ER), a chimeric fusion protein
      of PH domain-truncated Etk and ligand-binding domain of estrogen receptor, was
      introduced into MDA-MB-468 cells. Upon beta-estradiol ligand activation, the
      DeltaEtk-ER could stimulate Stat1 activity and confer cell apoptosis independent
      of EGF treatment. Taken together, our findings indicate that Etk is a downstream
      signaling molecule of EGF receptor and suggest that Etk activation is essential
      for transducing the EGF-induced apoptotic signaling.

PMID- 14676839
TI  - Expression analysis and genomic characterization of human melanoma
      differentiation associated gene-5, mda-5: a novel type I interferon-responsive
      apoptosis-inducing gene.
AB  - Melanoma differentiation associated gene-5 (mda-5) was identified by subtraction
      hybridization as a novel upregulated gene in HO-1 human melanoma cells induced to
      terminally differentiate by treatment with IFN-beta+MEZ. Considering its unique
      structure, consisting of a caspase recruitment domain (CARD) and an RNA helicase
      domain, it was hypothesized that mda-5 contributes to apoptosis occurring during
      terminal differentiation. We have currently examined the expression pattern of
      mda-5 in normal tissues, during induction of terminal differentiation and after
      treatment with type I IFNs. In addition, we have defined its genomic structure
      and chromosomal location. IFN-beta, a type I IFN, induces mda-5 expression in a
      biphasic and dose-dependent manner. Based on its temporal kinetics of induction
      and lack of requirement for prior protein synthesis mda-5 is an early type I IFN
      responsive gene. The level of mda-5 mRNA is in low abundance in normal tissues,
      whereas expression is induced in a spectrum of normal and cancer cells by IFN
      beta. Expression of mda-5 by means of a replication incompetent adenovirus,
      Ad.mda-5, induces apoptosis in HO-1 cells as confirmed by morphologic,
      biochemical and molecular assays. Additionally, the combination of Ad.mda-5+MEZ
      further augments apoptosis as observed in Ad.null or uninfected HO-1 cells
      induced to terminally differentiate by treatment with IFN-beta+MEZ. The mda-5
      gene is located on human chromosome 2q24 and consists of 16 exons, without
      pseudogenes, and is conserved in the mouse genome. Present data documents that
      mda-5 is a novel type I IFN-inducible gene, which may contribute to apoptosis
      induction during terminal differentiation and during IFN treatment. The conserved
      genomic and protein structure of mda-5 in human and mouse will permit analysis of
      the evolution and developmental aspects of this gene.

PMID- 14676840
TI  - Expression of an engrailed-LMO4 fusion protein in mammary epithelial cells
      inhibits mammary gland development in mice.
AB  - LIM domain factors and associated cofactors are important developmental
      regulators in pattern formation and organogenesis. In addition, overexpression of
      two LIM-only factors (LMOs) causes acute lymphocytic leukemia. The more recently
      discovered LMO factor LMO4 is highly expressed in proliferating epithelial cells,
      and frequently overexpressed in breast carcinoma. Here we show that while LMO4 is
      expressed throughout mammary gland development, it is dramatically upregulated in
      mammary epithelial cells during midpregnancy. The LMO coactivator Clim2/Ldb1/NLI
      showed a similar expression pattern, consistent with the idea that LMO4 and Clim2
      act as a complex in mammary epithelial cells. In MCF-7 cells, LMO4 transcripts
      were upregulated by heregulin, an activator of ErbB receptors that are known to
      be important in mammary gland development and breast cancer. To test the
      hypothesis that LMO4 plays roles in mammary gland development, we created an
      engrailed-LMO4 fusion protein. This fusion protein maintains the ability to
      interact with Clim2, but acts as a dominant repressor of both basal and activated
      transcription when recruited to a DNA-regulatory region. When the engrailed-LMO4
      fusion protein was expressed under control of the MMTV promoter in transgenic
      mice, both ductular development in virgin mice and alveolar development in
      pregnant mice were inhibited. These results suggest that LMO4 plays a role in
      promoting mammary gland development.

PMID- 14676841
TI  - Tetraspanin CD81 is linked to ERK/MAPKinase signaling by Shc in liver tumor
      cells.
AB  - Tetraspanins is a large family of membrane proteins that are implicated in cell
      proliferation, differentiation and tumor invasion. Specifically, the tetraspanin
      CD81 has been involved in cell proliferation but the mechanism is unknown. Here,
      we show that CD81 clustering stimulates ERK/MAPKinase activity and tyrosine
      phosphorylation of the adapter protein Shc in Huh7 cancer cells. In addition,
      overexpression of CD81 in HepG2 cells, NIH3T3 cells, and murine fibroblasts GD25
      lacking the beta1 family of integrins induces cell proliferation and
      ERK/MAPKinase activation. Linked with this event, we observed an increase in CD81
      associated type II phosphatidylinositol 4-kinase activity. A mutant in the PTB
      domain of Shc failed to interact with phosphoinositides and localize to the
      plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. Therefore,
      we conclude that CD81 stimulates synthesis of phosphoinositides with the
      recruitment of Shc to the plasma membrane via PTB domain, and this sequence of
      events induces activation of ERK/MAPKinase. These findings define a novel
      mechanism of ERK/MAPKinase activation and tumor cell proliferation.

PMID- 14676842
TI  - Characterization of human exonuclease 1 in complex with mismatch repair proteins,
      subcellular localization and association with PCNA.
AB  - Human exonuclease 1 (hEXO1) has been implicated in DNA mismatch repair (MMR),
      replication, and recombination, but the nature of its interaction with these
      cellular processes is still ambiguous. We show that hEXO1 colocalizes with
      proliferating cell nuclear antigen (PCNA) at DNA replication sites and that the C
      terminal region of hEXO1 is sufficient for this localization. We also show that
      both hMLH1-hPMS2 (MutLalpha) and hMLH1-hEXO1 complexes are formed in a reaction
      mixture containing all three proteins. Moreover, hEXO1 5' double-stranded
      exonuclease activity on a homoduplex substrate but not on a substrate containing
      a G/T mismatch was inhibited by complex formation with hMSH2-hMSH6 (MutSalpha) or
      MutLalpha. Taken together, the results support a model in which hEXO1 plays a
      role in events at the replication sites as well as a functional role in the MMR
      and/or recombination processes.

PMID- 14676843
TI  - Vascular endothelial growth factor-mediated activation of p38 is dependent upon
      Src and RAFTK/Pyk2.
AB  - Vascular endothelial growth factor (VEGF) induces activation of p38 mitogen
      activated protein kinase (MAPK) in primary endothelial cells and may be critical
      for VEGF-induced angiogenesis. We investigated the molecular basis for p38
      activation in response to VEGF. The expression of a C-terminal splice variant of
      FAK, FRNK, had no affect on VEGF-induced activation of p38; however, expression
      of a dominant-negative RAFTK/Pyk2 mutant led to a decrease in the activation of
      p38, but had no affect on extracellular signal-regulated kinase (ERK). Since
      calcium regulates RAFTK/Pyk2, we investigated its role in p38 activity.
      Preincubation with EGTA suppressed p38 activation, while calcium ionophore
      induced p38 activity. Inhibition of phospholipase C (PLC) resulted in complete
      inhibition of ERK, while having no affect on p38 activity. These data suggested a
      bifurcation in the regulation of MAPKs that occurs at the level of PLC and
      RAFTK/Pyk2 activation. Src family kinases interact with RAFTK/Pyk2. Inhibition of
      Src by either pharmacological or genetic means decreased p38 activity. Finally,
      we found that both Src and RAFTK/Pyk2 were essential for endothelial cell
      migration. These data identified a novel regulatory network involving
      extracellular calcium, RAFTK/Pyk2, Src and p38. This signaling network appears to
      be critical for VEGF-induced endothelial cell migration.

PMID- 14676844
TI  - Induction of p53-regulated genes in lung cancer cells: implications of the
      mechanism for adenoviral p53-mediated apoptosis.
AB  - The p53 gene is the most frequently mutated gene in human cancers. Loss of
      functional p53 leads to impaired responses of cancer cells to apoptosis induction
      and to poor prognosis in patients with certain types of cancer. Cancer gene
      therapies using ectopic expression of wild-type p53 to force cancer cells through
      the apoptotic pathway have been tested extensively preclinically and clinically,
      and genes in various cell lines have been reported to be regulated upon ectopic
      p53 overexpression. However, the effect of p53 on many other p53-dependent and
      apoptosis-related genes remains unclear, as does the mechanism of p53-induced
      apoptosis in human cancers. In this study, we used real-time reverse
      transcription polymerase chain reaction to evaluate the changes in expression of
      various p53-dependent and apoptosis-related genes in five human non-small-cell
      lung cancer cell lines with varying p53 statuses after adenoviral p53 treatment.
      We found that Ad/p53 induced the expression of the proapoptotic genes PUMA, Bak,
      Bax, and Fas in a cell type- and time-dependent manner. Among these genes, PUMA
      was upregulated the most dramatically and broadly. However, when a specific siRNA
      construct against PUMA was employed, we observed no attenuation of apoptosis in
      H1299 cells. Our data suggest that Ad-p53 induces the expression of a variety of
      proapoptotic genes and that lack of induction in one of these genes does not
      block Ad/p53-mediated cell killing in human lung cancer cells.

PMID- 14676845
TI  - Function analysis of estrogenically regulated protein tyrosine phosphatase gamma
      (PTPgamma) in human breast cancer cell line MCF-7.
AB  - Protein tyrosine phosphatase gamma (PTPgamma) is a member of the receptor-like
      family of tyrosine phosphatases and has been implicated as a tumor suppressor
      gene in kidney and lung cancers. Based on our previous findings, we hypothesize
      that PTPgamma is a potential estrogen-regulated tumor suppressor gene in human
      breast cancer. To examine the effects of PTPgamma on growth of MCF-7 human breast
      cancer cells and compare the estrogenic responses of human breast cells with
      different PTPgamma expression levels, we established several stably transfected
      MCF-7 cell lines expressing different levels of PTPgamma, which were confirmed by
      RT-PCR and immunostaining. In our work, we used the antisense construct to
      breakdown endogenous PTPgamma level in MCF-7 cells. The results from doubling
      time assay suggested that PTPgamma is capable of inhibiting MCF-7 breast cancer
      cell growth. We further demonstrated that PTPgamma is able to inhibit anchorage
      independent growth of breast cancer cells in soft agar and reduce the estrogenic
      responses of MCF-7 cell proliferation to estradiol-17beta (E(2)) and zeranol (Z,
      a nonsteroidal growth promoter with estrogenic activity). Our data suggest that
      PTPgamma may function as an important modulator in regulating the process of
      tumorigenesis in human breast.

PMID- 14676846
TI  - Negative regulation of SCFSkp2 ubiquitin ligase by TGF-beta signaling.
AB  - TGF-beta is a multifunctional growth factor whose best-known function is to
      inhibit cell growth and suppress tumor formation. TGF-beta causes cells to
      accumulate in mid-to-late G1 phase by blocking the transition from G1 to S. It
      has been shown that TGF-beta inhibits Cdk2-cyclin E kinase activity by promoting
      the binding of cell cycle inhibitor p27Kip1 to the kinase complexes. Here, we
      show that TGF-beta treatment leads to stabilization of p27Kip1 during G1 to S
      transition. We found that TGF-beta negatively regulates components of the SCF
      complex, which degrades the p27Kip1 during the G1 to S transition, through two
      distinct mechanisms. Using a pulse-chase analysis, we demonstrated that the
      stability of Skp2 decreases in the presence of TGF-beta. Destabilization of Skp2
      by ubiquitin-mediated proteolysis was also demonstrated that in an in vitro
      degradation system, using cell extracts prepared from TGF-beta-treated cultured
      cells. In addition, TGF-beta treatment decreases the levels of Cks1 mRNA. The
      deficiency of Cks1 in TGF-beta-treated cells likely contributes to the
      stabilization of p27Kip1 and destabilization of Skp2, because in the absence of
      Cks1, SCFSkp2 cannot ubiquitinate p27Kip1; instead, self-ubiquitination of Skp2
      occurs. Thus, stabilization of the cell cycle inhibitor p27Kip1 and cell growth
      inhibition in response to TGF-beta occur in part through limiting the threshold
      of the SCFSkp2 ubiquitin ligase by transcriptional and post-transcriptional
      mechanisms.

PMID- 14676847
TI  - Persistence of abnormal neural responses to a meal in postobese individuals.
AB  - OBJECTIVE: To determine whether abnormal obese-like neural responses to a meal
      persist in postobese individuals, who achieved and maintained a normal body
      weight despite a past history of severe obesity. DESIGN AND SUBJECTS: Cross
      sectional study of the brain's response to tasting and consuming a satiating meal
      in 11 postobese (age: 40+/-6 y, body mass index (BMI): 23.6+/-1.9 kg/m(2)), 23
      obese (age: 29+/-6 y, BMI: 39.6+/-3.8 kg/m(2)) and 21 lean (age: 33+/-9 y, BMI:
      22.8+/-2.1 kg/m(2)) subjects. MEASUREMENTS: Regional cerebral blood flow (rCBF, a
      marker of neural activity) at baseline (after a 36-h fast), after tasting and
      after consuming a satiating liquid meal was assessed using positron emission
      tomography and state-dependent changes (taste-baseline; satiation-baseline), and
      compared across groups. Subjective ratings of hunger and fullness were measured
      by a visual analogue scale and body fatness by dual-energy X-ray absorptiometry.
      RESULTS: In response to tasting the liquid meal, changes in rCBF were different
      in the obese as compared to the lean individuals (P<0.05, corrected for multiple
      comparisons) in the middle insula (peak voxel, x=-41, y=1, z=8; Montreal
      Neurological Institute coordinates) and posterior cingulate cortex (peak voxel,
      x=17, y=-47, z=40). The middle insular cortex exhibited a similar increase of
      neural activity in the obese and postobese subjects, whereas in the lean subjects
      the regional activity did not change. In the posterior cingulate cortex, the
      changes in rCBF in the postobese subjects were not different from those in the
      other groups. In response to a satiating amount of the same liquid meal, changes
      in rCBF were different in the obese as compared to the lean individuals (P<0.05,
      corrected for multiple comparisons) in the posterior hippocampus (peak voxel,
      x=21, y=-45, x=4), posterior cingulate cortex (peak voxel, x=17, y=-47, z=40),
      and amygdala (peak voxel, x=27, y=1, z=-24). The posterior hippocampus exhibited
      a similar decrease of neural activity in the obese and postobese subjects,
      whereas in the lean subjects the regional activity increased. In the posterior
      cingulate cortex and amygdala, the changes in rCBF were not different between the
      postobese and lean individuals. None of the changes in neural activity were
      correlated with the age of the individuals, the subjective ratings of hunger and
      fullness, or the meal induced-changes in plasma glucose, insulin, or serum free
      fatty acids. CONCLUSION: Persistence of abnormal neural responses to a meal in
      the postobese individuals, a group at high risk for relapse, indicates that a
      predisposition to obesity may involve areas of the brain that control complex
      aspects of eating behavior including anticipation and reward, chemosensory
      perception, and autonomic control of digestion (insular cortex), as well as
      enteroception and learning/memory (hippocampus).

PMID- 14676848
TI  - Dietary restraint and the mis-reporting of anthropometric measures by middle-aged
      adults.
AB  - OBJECTIVE: To assess whether levels of dietary restraint are associated with mis
      reporting measures of adiposity by middle-aged adults. DESIGN: Cross-sectional
      study of middle-aged men and women, the parents of a group of young adults
      followed up since birth. METHODS: In all, 631 couples were mailed questionnaires
      and asked to record their height, weight and waist circumference. A paper tape
      measure with instructions for use was attached. Couples also completed the
      dietary restraint section of the Dutch Eating Behaviour Questionnaire, and
      provided information on employment and lifestyle habits. A subsample of
      participants was then invited to attend a clinic where detailed anthropometric
      measures were taken. RESULTS: In all, 435 women (69%) and 332 men (55%) completed
      the questionnaire; of those invited, 182 (85%) women and 102 (61%) men attended a
      clinic session. Regression analyses showed that the dietary restraint score was
      associated with the mis-reporting of BMI by women (P<0.01), but not men (test for
      interaction with gender, P=0.11). In women, the difference between the measured
      and reported BMI increased by 0.36 kg/m(2) (0.11-0.61) per unit increase in
      restraint score. This association was independent of age, smoking, social class,
      slimming, exercise frequency or television viewing time, but was attenuated in
      models controlling for measured BMI. The dietary restraint score was not
      associated with mis-reporting of waist circumference in men or women.
      CONCLUSIONS: Dietary restraint score may be a useful tool for identifying
      individuals more likely to mis-report anthropometric measurements, although
      associations may vary by gender.

PMID- 14676850
TI  - [Lung transplant in children].
AB  - OBJECTIVE: This article presents a review of the main aspects related to lung
      transplant in children and shows the experience of the first medical team to
      perform this procedure in Latin America. SOURCES: Literature review of scientific
      articles, using the MEDLINE and Lilacs databases. SUMMARY OF THE FINDINGS: The
      article was organized into topics. Similarities and differences regarding lung
      transplant in adults were identified. Specific problems presented by children
      subjected to transplant are discussed, and special emphasis is given to a
      specific situation: lung transplant with living related donors. CONCLUSIONS:
      Advances in adult lung transplant for the treatment of parenchymatous or vascular
      lung diseases have been successfully employed in the pediatric population during
      the last few years.

PMID- 14676851
TI  - [Asthma and allergic rhinitis as symptoms of the same disease: a paradigm under
      construction].
AB  - OBJECTIVE: To describe current ideas about the relation between upper and lower
      respiratory tract and to review the epidemiological, immunological, and
      pathological aspects that support the paradigm of united airways disease.
      SOURCES: Literature review using the Medline, MD Consult, HighWire, Medscape and
      Lilacs databases. We used allergic rhinitis and asthma as keywords, and searched
      articles published in the past 20 years. SUMMARY OF THE FINDINGS: Epidemiological
      evidence includes prevalence of allergic rhinitis in asthmatic patients and vice
      versa, results of cross-sectional studies, bronchial hyperresponsiveness in
      patients with allergic rhinitis, importance of genetic and environmental factors,
      and the age of onset of atopic disease. Morphological and physiological aspects
      show structural differences between the nasal and bronchial mucosa, and the
      mechanisms that could explain the effect of rhinitis on asthma. Immunological
      aspects including the participation of bone marrow in the production of
      inflammatory cells and allergic reactions after allergen challenge are the same
      in allergic rhinitis and asthma. Finally, the results of the therapy for allergic
      rhinitis in bronchial hyperresponsiveness and in clinical and functional control
      of asthma are also reported. CONCLUSIONS: Epidemiological evidence and
      immunological and pathological aspects suggest that there is a relation between
      allergic rhinitis and asthma. The paradigm of united airways disease suggests the
      implementation of an integrated therapeutic approach.

PMID- 14676852
TI  - [Etiological diagnosis of pneumonia--a critical view].
AB  - OBJECTIVES: To search literature related to the etiological diagnosis of acute
      pneumonia in children. SOURCES: Systematic review of Medline and Lilacs
      databases. SUMMARY OF THE FINDINGS: The use of new diagnostic methods such as
      immunological techniques and polymerase chain reaction has proven invaluable for
      specific diagnosis and epidemiological investigation, showing adequate
      sensitivity, specificity and promptness of results, with the aim of guiding
      therapy properly. Review of epidemiological studies of community acquired
      pneumonia showed that Streptococcus pneumoniae is still one of the most
      significant etiologic agents in all age groups, in developing and industrialized
      countries. Resistance of this agent to penicillin and cephalosporins is
      increasing in all continents and is worrisome. Atypical agents such as Mycoplasma
      pneumoniae and Chlamydia pneumoniae are common in community acquired pneumonia,
      mainly in children older than 4 years, representing one third of the cases in
      industrial countries. However, their prevalence in developing countries remain to
      be determined. Respiratory syncytial virus is also a very common etiology of
      community acquired pneumonia and may cause severe infections, mainly in infants
      and younger children. The introduction of new conjugated vaccines for
      Streptococcus pneumoniae and Haemophilus influenzae type b resulted in
      significant reduction of morbidity and mortality of pneumonia in children.
      CONCLUSIONS: A significant impact on morbidity and mortality of acute pneumonia
      in children is likely to occur if microbiological and antimicrobial control is
      continuously and dynamically performed, thus allowing for the development of new
      vaccines, particularly against the respiratory syncytial virus.

PMID- 14676853
TI  - [Prophylactic treatment of asthma].
AB  - OBJECTIVE: To review basic concepts, inhalation therapy, classification of asthma
      and peculiarities of asthma in developing countries. SOURCES: Direct search in
      the Medline, HighWire and MD Consult databases. SUMMARY OF THE FINDINGS: Inhaled
      corticosteroids are the drugs of choice for the treatment of asthma.
      Alternatively, other drugs, such as long-acting beta-agonists and
      antileukotrienes could be considered. CONCLUSIONS: At an individual level, asthma
      treatment presents a satisfactory outcome. However, the great challenge for
      public health professionals and authorities is to provide treatment for asthmatic
      patients from low-income families living in developing countries.

PMID- 14676854
TI  - [Controversies in the pharmacological management of acute asthma in children].
AB  - OBJECTIVE: To present a review of controversial issues related to the
      pharmacological management of the treatment of acute asthma in children. SOURCES:
      Articles published in national and international scientific journals. Data were
      selected from Lilacs and Medline databases. SUMMARY OF THE FINDINGS: The article
      was organized into topics, presenting aspects on which there is consensus
      regarding the pharmacological treatment of asthma in children. Issues related to
      the use of metered dose inhaler versus nebulizers, the role of beta2-adrenergic
      drugs administered intravenously as well as the role of methylxanthine and
      magnesium sulfate are approached critically. CONCLUSIONS: Inhaled beta2-agonist
      drugs combined with corticosteroids remain the treatment of choice for acute
      episodes of asthma in children. Either nebulizers or metered dose inhalers
      connected to spacers are efficient for the relief of acute symptoms. Patients who
      are refractory to conventional treatment and develop severe acute asthma should
      receive beta2-agonist drugs intravenously, provided they are properly monitored.
      Methylxanthine and magnesium sulfate should be considered a second choice for
      selected patients.

PMID- 14676855
TI  - [Surgical treatment of parapneumonic pleural effusion and its complications].
AB  - OBJECTIVE: Surgical treatment of parapneumonic pleural effusion in children is
      controversial. The type of intervention is based mainly on personal experience
      and on the small number of reported cases. This article aims at presenting a
      literature review and the authors experience in the surgical management of
      parapneumonic pleural effusion in children. SOURCES: Data were searched in the
      Medline and Lilacs databases. SUMMARY OF THE FINDINGS: Complicated parapneumonic
      effusion should be surgically drained if thoracentesis reveals the presence of
      pus, positive Gram stain or culture, or pH less than 7.0 or glucose less than 40
      mg/dl. The surgical drainage depends on the stage of parapneumonic pleural
      effusion: at the acute stage closed thoracostomy drainage is enough; at the
      fibrinopurulent stage thoracoscopy is indicated; at organizational stage
      thoracotomy can be performed in children with stable anesthetic conditions, and
      open thoracostomy drainage should be used in patients in a poor state of health.
      Echography is very important to evaluate the staging of parapneumonic effusion.
      CONCLUSIONS: Surgical treatment of complicated parapneumonic effusion should be
      done as early as possible, and the kind of procedure depends on the stage of
      pleural effusion. In children with complicated parapneumonic effusion echography
      is very important to evaluate the staging of parapneumonic effusion.

PMID- 14676856
TI  - [Controversies in cystic fibrosis--from pediatrician to specialist].
AB  - OBJECTIVE: Cystic fibrosis has become, in the last 70 years, the most important
      potentially fatal inherited disease that affects white individuals around the
      world. Although it is considered a genetic disorder, which strikes cells of
      different organs, not all patients present similar clinical response. Many
      clinical manifestations, mainly pulmonary and gastrointestinal, may develop in
      cystic fibrosis patients. The aim of this article is to offer pediatricians an
      updated review of the controversies and recent advances in the treatment of
      cystic fibrosis. SOURCES: Systematic review in the Medline database. SUMMARY OF
      THE FINDINGS: Seventy-nine articles about cystic fibrosis published in
      international journals were reviewed. This article presents an updated and
      critical review of the main events related to the incidence, pathophysiology,
      diagnosis and treatment of cystic fibrosis. CONCLUSIONS: Even though no treatment
      is available for this disease, new findings about its etiology and
      pathophysiology have been discovered in the last two decades, improving treatment
      and survival of cystic fibrosis patients.

PMID- 14676857
TI  - [Respiratory sequelae of viral diseases: from diagnosis to treatment].
AB  - OBJECTIVE: The objective of the present article is to present a review of the
      main clinical issues faced by pediatricians while defining the diagnosis,
      management and prognosis of postinfectious bronchiolitis obliterans. SOURCES:
      Data from national and international scientific journals selected from the Lilacs
      and Medline databases. SUMMARY OF THE FINDINGS: With the purpose of establishing
      the diagnosis, a radiological investigation shows high levels of pulmonary
      insufflation, thickened bronchovascular bundles and, less often, bronchiectasis,
      atelectasis and pulmonary hyperlucency. The CT exam allows the visualization of
      structural and functional findings, such as air trapping, bronchiectasis and
      mosaic pattern. Lung function tests in children and infants always reveal
      significant reduction of expiratory flows. Pulmonary biopsy is not mandatory in
      order to confirm bronchiolitis obliterans. Diagnosis can be established through
      the combination of history of bronchiolitis, chronic obstructive pulmonary
      disease and typical tomographic findings. The treatment used by most services
      includes oral and inhaled corticosteroids and bronchodilators for long periods.
      The management of exacerbated conditions often requires antibiotics and physical
      therapy. CONCLUSIONS: Most patients present a favorable outcome with slow
      improvement of the pulmonary function and reduced necessity for supplementary
      oxygen. Some patients present progressive worsening of hypoxemia and CO2
      retention, which leads to pulmonary hypertension and cor pulmonale.
      Postinfectious bronchiolitis obliterans is mild and moderate in most patients,
      with consequent good prognosis and low mortality.

PMID- 14676858
TI  - [Vaccination and the respiratory tract--what should we know?].
AB  - OBJECTIVE: This article aims at presenting a review of the main vaccines used in
      the pediatric population with direct impact on the prevention of infectious
      processes of the respiratory tract in children. SOURCES: Data from articles
      published in national and international scientific journals. The data were
      selected by means of direct search or search in the Lilacs and Medline databases.
      SUMMARY OF THE FINDINGS: This article was structured in topics, presenting issues
      related to immunization against frequent pathogens of the respiratory tract in
      human beings: Haemophilus influenza, influenza virus, respiratory syncytial virus
      and Streptococcus pneumoniae. CONCLUSIONS: The prevention of respiratory diseases
      through immunization is one of the main measures for the control of respiratory
      infection. These new vaccines, especially against Haemophilus influenza, have
      been available for some years with acknowledged efficacy. Now, the vaccine
      against Streptococcus pneumoniae (heptavalent vaccine) leads to a new perspective
      towards the management of respiratory diseases in children. In risk populations,
      the control of viral diseases through immunization, actively against the
      influenza virus and passively against the syncytial respiratory virus, is also an
      efficient measure to reduce respiratory disease.

PMID- 14676859
TI  - [Diagnosis and treatment of tuberculosis in children--an updated review of an old
      problem].
AB  - OBJECTIVE: Tuberculosis is still one of the most severe chronic diseases,
      especially in the world's poorest regions. Developing countries still have to
      face serious problems related to this endemic disease, in spite of the control
      programs they have implemented. The present study aims at updating the diagnosis
      and treatment of tuberculosis in three South American countries: Brazil, Chile
      and Argentina. SOURCES: Medline and Lilacs databases, official guidelines and
      consensuses of the three countries involved. SUMMARY OF THE FINDINGS: Brazil,
      Chile and Argentina have guidelines based on the World Health Organization
      documents and on international consensuses. The standardization is similar
      between these countries, allowing the unification of language and favoring
      control measures. Within the Brazilian context, the new guidelines on the
      treatment of tuberculosis set out by the Ministry of Health are presented.
      CONCLUSIONS: Since each country had to make adaptations in an attempt to solve
      the epidemiological differences between them, the treatments against tuberculosis
      still present some discrepancies, such as the use of three or four drugs in some
      cases.

PMID- 14676860
TI  - [Exogenous surfactant therapy--what is established and what still needs to be
      determined].
AB  - OBJECTIVE: To review well-known aspects of exogenous surfactant therapy, and to
      discuss controversial points regarding the current state of research. SOURCES:
      Review of the literature, using Medline and Cochrane Database Library, in
      association with the authors' experience in relation to exogenous surfactant
      replacement therapy. SUMMARY OF THE FINDINGS: The main aspects of surfactant
      characteristics: composition, pool, metabolism, inactivation and immediate
      effects after its administration are well established. However, there are some
      doubts related to the use of exogenous surfactants that need to be cleared up:
      choice of surfactant type, most appropriate length of treatment, adequate dose
      and number of doses, best administration route and complications associated with
      its use. Currently, the research about exogenous surfactant therapy focuses on
      two aspects: the use of surfactant in other pathologies besides the respiratory
      distress syndrome of the newborn, and the development of new surfactants through
      the addition of proteins or analogous proteins, with the aim of improving its
      action and reducing its inactivation. CONCLUSIONS: The use of exogenous
      surfactant has become a routine in neonatal intensive care units, but both
      clinical and experimental research is still necessary.

PMID- 14676861
TI  - [Diagnosis and treatment in pediatric neurology]

PMID- 14676862
TI  - [Treatment of headaches]
AB  - OBJECTIVE: To perform a bibliographic review about headache treatment in
      childhood and adolescence. SOURCES: Articles were searched through Medline
      database using the terms: migraine, or headache, childhood, or adolescence, and
      treatment, during the period between 1966 and 2001. Review articles and case
      reports were excluded. Only articles dealing with pharmacological, and non
      pharmacological treatment of primary headaches were selected. SUMMARY OF THE
      FINDINGS: A total of 104 articles were found; only those reporting results of the
      case-control studies, or drug vs. placebo, either blind, or open, and that
      included children, or adolescents were selected. CONCLUSIONS: Only a few
      controlled studies about the headache treatment were found in the pediatric age
      group, although primary headaches are frequently seen in clinical practice.
      Therefore they constitute an important subject to be studied. Only a few drugs
      were adequately studied, and in a small number of studies. Both acute and
      prophylactic treatment were addressed.

PMID- 14676863
TI  - [Treatment of febrile seizures]
AB  - OBJECTIVE: To review basic concepts of febrile seizures and the indications of
      specific tests. To analyze the prognosis and the medical treatment. SOURCES: The
      author reviewed the literature and presented her published data. SUMMARY OF THE
      FINDINGS: The key points are based on the rules of the American Academy of
      Pediatrics designed according to a consensus about when and how to investigate
      febrile seizures, and indications of treatment. CONCLUSIONS: Febrile seizure is a
      benign entity and most children will present only one seizure during their lives.
      There is no indication of complementary tests (electroencephalogram, lumbar
      puncture and neuroimaging tests) and specific treatment for this group of
      children. Special indications are revised.

PMID- 14676864
TI  - [Management of the first convulsive seizure]
AB  - OBJECTIVE: To observe the wide variety of reported prognosis after a first
      unprovoked convulsion and of risk factors that are associated with recurrence,
      and a uniform conduct. SOURCES: Systematic review of Bireme. SUMMARY OF THE
      FINDINGS: Recurrence rates differ from a first seizure study because of different
      inclusion criteria. The EEG is particularly helpful to support the epileptic
      nature of the event in younger patients and in those with seizures of unknown
      origin. An abnormal EEG, particularly the ones with generalized spike-wave
      discharges, has been reported as a consistent predictor of recurrence. Although
      not a substitute for the clinical examination, the EEG is an integral part of the
      diagnostic process after the first afebrile seizure and should be requested. The
      actual decision regarding whether or not to treat patients who present an initial
      seizure depends heavily on the physicians assessment of the potential morbidity
      of another seizure versus the potential morbidity of antiepileptic drugs (AEDs)
      therapy. CONCLUSIONS: In children, side effects of AEDs are common, and the risk
      of injury from a seizure is usually minimal because children neither drive nor
      operate heavy machinery and are usually in supervised environment. Regarding
      adults, there is little unanimity.

PMID- 14676865
TI  - [Treatment of epilepsy in childhood]
AB  - OBJECTIVE: Due to the development of new antiepileptic drugs, epilepsy treatment
      has presented substantial progress in the last decade. In spite of presenting
      more adequate profile, these drugs have not shown better efficiency in seizure
      control than the traditional drugs. The objective of this revision is to provide
      up-to-date data for the treatment of epilepsy in childhood and the role of the
      new antiepileptic drugs. SOURCES: Bibliographic review has been performed at
      Medline for the last 10 years, and the most pertinent papers and abstracts
      presented in International Epilepsy Meetings were selected. SUMMARY OF THE
      FINDINGS: The new antiepileptic drugs could be indicated in the treatment of some
      specific epileptic syndromes. Serious side effects have been described with the
      use of these drugs. CONCLUSIONS: The traditional drugs must be considered as the
      primary choice in the treatment of ordinary epilepsy.

PMID- 14676866
TI  - [Surgical treatment of epilepsies in children]
AB  - OBJECTIVE: To review the literature on surgical treatment of epilepsy in
      children. SOURCES: This review article is based on critical analysis of
      literature concerning epilepsy surgery for children. SUMMARY OF THE FINDINGS: In
      children and adolescents, developmental abnormalities and low-grade tumors
      predominate as causes and types of epilepsies. Extratemporal resections and
      hemispherectomies are common in pediatric series, and hippocampal sclerosis is
      rare. Seizure-free outcome is significantly less frequent after extratemporal or
      multilobar resection than after temporal resection in children than in adults,
      but the results are gratifying in both groups. Also, a global outcome, including
      parental satisfaction, developmental and social outcome, as well as activities of
      daily living (ADL), schooling, and behavioral changes should be considered.
      Pediatric epilepsy surgical series show that 60-100% of the patients have a good
      seizure outcome. Roughly 30 to 40% of patients improve some aspects of their
      behavior such as attention, aggressiveness, and hyperactivity and 16% of those
      start to attend school after surgery. Parents noted improvement of their social
      life in about 2/3 of children. CONCLUSIONS:Surgery for epilepsy has now become a
      realistic therapeutic option for selected children and the field is likely to
      increase in the near future. Surgical therapy should not be considered unless
      there is a reasonably good chance of improving the patientacute;s quality of
      life.

PMID- 14676867
TI  - [Management of head injury in children]
AB  - OBJECTIVE: To make pediatricians aware of ideas about how to handle head injury
      in children under and over 2 years of age, to facilitate understanding and to
      allow a rethinking about the necessary care when attending children with head
      injury. SOURCES: A bibliographic review of the theme based on Medline. SUMMARY OF
      THE FINDINGS: The following aspects were analyzed: the overall epidemiological
      aspects, the concept and the physiopathology of the damage caused by brain
      trauma. The assessment of the severity of head injury for different age ranges
      was discussed, as well as the opinion of various authors and the current ideas
      about the criteria regarding hospitalization, request for supplementary exams and
      therapeutic approach. The value of neuroimaging exams in cases of head injury
      and, finally, the prevention strategies and conclusions also were discussed.
      CONCLUSIONS: In most cases, head injuries in children are rated as not being
      severe. Nevertheless, even though they are seen as slight, when considering the
      pediatric population the clinical picture is often asymptomatic presenting
      neuroimaging changes, the management of head injury at this age range is
      different from the management in adults.

PMID- 14676868
TI  - [Cerebral palsy, new therapeutic possibilities]
AB  - OBJECTIVE: To provide pediatrician with updated information about diagnoses and
      treatment of cerebral palsy. This articles aims at supplying pediatricians with
      tools that will help them diagnose and treat cerebral palsy. SOURCES: Non
      systematic review of literature combined with personal experience at the
      Neurology Unit of Pediatrics Service of Hospital de Clinicas de Porto Alegre -
      Universidade Federal do Rio Grande do Sul. SUMMARY OF THE FINDINGS: The cerebral
      palsy diagnosis and treatment are based on multidisciplinary clinical exam, EEG,
      CT and MR. CONCLUSIONS: Pediatricians are the first physician that see the
      patient with cerebral palsy. Thus, they should be able to diagnose an treat it.

PMID- 14676869
TI  - [Neurological manifestation and genetic diagnosis of Angelman, Rett and Fragile-X
      syndromes]
AB  - OBJECTIVE: To discuss clinical and electroencephalographic aspects and the
      genetic mechanisms of three neurogenic syndromes that can be related to nosologic
      entities in the heterogenic pathological group presenting symptoms of mental
      retardation and autism. SOURCES: The authors carried out a bibliographic review
      on each syndrome involved, correlating and characterizing the neurological
      manifestations, as well as describing genetic mechanisms and identifying
      biological markers. SUMMARY OF THE FINDINGS: The authors were able to confirm
      that Rett Sydrome is a genetic disease resulting from the mutation of the MECP2
      gene and clinical variations can be explained by different mutations in this
      gene. Angelman syndrome has four genetic mechanisms responsible for phenotypic
      variations and different risks of recurrence. In Fragile-X syndrome, the degree
      of cognitive impairment is related to the number of trinucleotide repeats.
      CONCLUSIONS: Different genetic mechanisms of the three syndromes are responsible
      for clinical variability. By identifying the biological markers, the diagnosis
      will be performed earlier and it will be possible to identify new subtle
      expressions of the disease.

PMID- 14676870
TI  - [Sleep disorders]
AB  - OBJECTIVE: The aim of this article is to review and update the knowledge about
      sleep disorders in childhood. SOURCES: Normal sleep ontogenesis and therapeutics
      for the most prevalent sleep disorders were reviewed. The text was based on
      classical articles and books and on Medline (publications from 2000 and 2001)
      using the key words sleep disorders and childhood. the article was structured on
      descriptive topics containing definition of the sleep disorder, age, clinical
      presentation and therapeutics. SUMMARY OF THE FINDINGS: Sleep disorders are
      frequent concerns referred in pediatrics outpatient clinics, and a correct
      diagnosis is the main goal to establish therapeutic procedures. CONCLUSIONS: In
      the majority of cases clinical history is sufficient to establish diagnosis and
      assuring parents of the benign evolution of the symptoms the better treatment.

PMID- 14676871
TI  - [Paroxysmal non-epileptic events]
AB  - OBJECTIVE: This article aims at reviewing one of the most important problems
      faced by pediatricians in the field of child neurology. The paroxystic non
      epileptic events are also a frequent reason for pediatric neurology consultations
      and admission for diagnostic videoelectroencephalogram monitoring. SOURCES:
      Literature review on the subject was perform on Medline, data were also collected
      from the main Pediatric Neurology Textbooks, which were found to be an important
      and unique source of information on the subject. SUMMARY OF THE FINDINGS: Many of
      the entities discussed in this paper are very common in the pediatric population
      such as syncope, breath-holding spells and the movement disorders associated with
      gastroesophageal reflux. Other syndromes are less frequent such as the paroxysmal
      dystonias and the Segawa Syndrome (dystonia with diurnal variation). CONCLUSIONS:
      The basic knowledge of these syndromes is very important since it may avoid
      unnecessary procedures and the wrongful diagnosis of epilepsy. Patients who are
      mistakenly diagnosed as epileptics are exposed to anticonvulsant medications,
      which are probably not going to be effective and may expose them to the risk of
      side effects.

PMID- 14676872
TI  - [Neuromuscular disorders]
AB  - OBJECTIVE: To discuss the most important aspects for the performance of a
      differential diagnosis among the main neuromuscular disorders in children, which
      include diseases affecting the motor unity, i.e. spinal motor neurons, peripheral
      nerves, neuromuscular junction and muscular fibers. SOURCES: The review of the
      clinical aspects that should be considered for a prompt differential diagnosis
      among several neuromuscular disorders as well as between those and the main
      causes of secondary muscular hypotonia due to central nervous system or systemic
      disturbances is based on the clinical experience acquired along the last 12 years
      in following-up children with Neuromuscular Disorders attended at the outpatient
      Service of Neuromuscular Disorders at the Hospital das Clinicas da Faculdade de
      Medicina da Universidade de Sao Paulo. In addition, it is based on Medline and on
      the review of the most recent numbers of Neuromuscular Disorders, the official
      journal of the World Muscle Society. SUMMARY OF THE FINDINGS: Most of
      neuromuscular disorders are genetic conditions in children and the most common of
      them are Xlinked Progressive Muscular Dystrophy of Duchenne, Spinal Muscular
      Atrophy, Congenital Muscular Dystrophy, Myotonic Dystrophy and Congenital
      Myopathies. CONCLUSIONS: Due to the phenomenal development in human molecular
      genetics the pathogenesis of several neuromuscular disorders in children has been
      clarified over the last decade. Nowadays many new diagnostic methods, including
      techniques of fetal diagnosis, and a more objective genotype-phenotype
      correlation as well as classification are available.

PMID- 14676873
TI  - [Management of learning disorders and attention deficit in children]
AB  - OBJECTIVE: This review aims at providing pediatricians with an update on the main
      causes involved in low school achievement. A more detailed approach is given for
      the management and treatment of attention deficit hyperactive disorder. SOURCES:
      Data was obtained by a systematic review of published literature in Medline,
      through a search on Pubmed in the last five years. The key words used were
      learning disability, attention deficit, dyslexia (reading disorder) and
      dyscalculia (mathematical disorder). Studies focusing evaluation and management
      were retrieved. Governmental population educational data on literacy was also
      included. SUMMARY OF THE FINDINGS: Statistical medical Brazilian data on the
      subject is scarce. Hearing, visual and mental deficiency, together with attention
      deficit hyperactive disorder and specific learning disorders should be part of
      the differential diagnosis of children with poor school achievement. Development
      should be carefully followed until school entrance, particularly in children at
      risk. CONCLUSIONS: Therapy with stimulants, anti-depressive drugs or cloninidine
      with multimodal treatment improves school achievement in children with attention
      deficit hyperactive disorder.

PMID- 14676874
TI  - [Teaching and healthcare in adolescence: reality and perspectives]

PMID- 14676875
TI  - [Risk behavior in adolescence]
AB  - OBJECTIVE: The present article reviews the methods and criteria used to assess
      risk behavior in adolescents. METHODS: Non-systematic review of scientific
      literature, as well as the assessment of the clinical and research experience
      accumulated by the Adolescent Outpatient Clinic of the Hospital de Clinicas de
      Porto Alegre. RESULTS: Physicians can apply a comprehensive healthcare model by
      using a psychosocial approach, trying to understand the influence the media
      exerts on adolescents, and trying to establish a confidentiality relationship
      with them. The major factors that should be evaluated regarding risk behavior
      among adolescents include clinical and nutritional aspects, as well as sexuality,
      violence, mental health and alcohol and drug use issues. CONCLUSIONS: Health care
      providers should use their sensitivity and expertise, in addition to establishing
      ethically clear approaches to evaluate risk factors. The authors suggest a route
      of investigation of risk behavior that should be used in routine consultation.

PMID- 14676876
TI  - [Clinical assessment of sexual maturation in adolescents]
AB  - OBJECTIVE: To present the methods for clinical evaluation of sexual maturation in
      adolescents. METHODS: Bibliographic review concerning the practice of pubertal
      staging. RESULTS: The assessment of sexual maturation is an essential step in the
      comprehensive health care of adolescents, allowing for the evaluation of their
      developmental stage. In addition, this assessment allows establishing a
      correlation between different pubertal events, following up diseases, and
      interpreting laboratory tests appropriately. Pubertal stage is assessed by the
      examination of breasts and pubic hair in females, and genitals and pubic hair in
      males. A new photographic standard for pubertal staging and a new method for
      clinical measurement of testicular volume are presented. CONCLUSIONS: The
      assessment of sexual maturation is an important feature in the health care of
      adolescent patients and must be included in the clinical practice of
      pediatricians involved in adolescent medicine.

PMID- 14676877
TI  - [Pulmonology in adolescence]
AB  - OBJECTIVE: To review concepts, long-term treatment schemes and peculiarities of
      the approach to adolescents with respiratory allergy, asthma and/or allergic
      rhinitis. METHODS: The data were obtained by systematic revision of studies
      published in the BIREME database between 1990 and 2001. RESULTS: Most teenagers
      with asthma and/or rhinitis prefer to view their disease as episodic and do not
      accept the need for regular medication. These factors combined with the fear of
      being different from their peer group are responsible for poor treatment
      adherence. CONCLUSIONS: It is extremely important that adolescent patients
      affected by asthma and/or allergic rhinitis be well-informed about their
      condition and receive proper medication; however, the following should also be
      considered: 1) open communication between the clinician and adolescent patients
      2) inquiry into the fears and anxieties of the patient 3) shared responsibility
      for the treatment.

PMID- 14676878
TI  - [Atherosclerotic risk factors in adolescence]
AB  - OBJECTIVE: To assess the impact of atherosclerotic risk factors on adolescence.
      METHODS: Nonsystematic literature review. RESULTS: The progression and severity
      of atherosclerosis are related to the presence (number), magnitude and duration
      of some risk factors. CONCLUSIONS: Preventive health measures should be early
      implemented in order to ensure a healthy childhood and adolescence, and avoid
      future cardiovascular disease.

PMID- 14676879
TI  - [Urinary infection in adolescents]
AB  - OBJECTIVE: Urinary tract infections are caused by various gram-negative bacteria.
      Escherichia coli is the most common causative agent in all groups of patients.
      Staphylococcus saprophyticus is now recognized as a common cause of urinary tract
      infection in adolescents and young adult women. METHODS: Review of literature and
      clinical experience with urinary tract infections in adolescents at the Pediatric
      Nephrology Department of Hospital Santa Casa de Sao Paulo. RESULTS: Lower urinary
      tract infection, hematuria and dysuria were the most frequent symptoms observed
      in infections caused by Staphylococcus saprophyticus. Some asymptomatic cases
      were observed. The infection may be associated with adverse effects of maternal
      and fetal health during pregnancy. CONCLUSIONS: This article reviews the
      diagnosis, etiology, treatment, and complications associated with urinary tract
      infections in adolescents.

PMID- 14676880
TI  - [Contraception and pregnancy in adolescence]
AB  - OBJECTIVE: To review and discuss different contraceptive methods currently used
      by adolescents, and also discuss adolescent pregnancy, including the associated
      risks and the importance of prenatal care. METHODS: Review of literature and
      clinical experience with different contraceptive methods and with adolescent
      pregnancy. RESULTS: The oral contraceptive pill is the most common method used by
      teenagers due to its low failure rate and other non-contraceptive effects.
      Emergency contraception is a good option in cases of rape, unplanned sexual
      intercourse, condom rupture, nonuse of oral contraceptives during short
      intervals. In this case, the pill should be taken within 72 hours after the
      intercourse (preferably before 24 hours for best effect). Most problems related
      to adolescent pregnancy have a social or economic origin; however, some medical
      complications such as preterm labor and anemia are frequently reported.
      CONCLUSIONS: The use of male and female condoms combined with other contraceptive
      methods should be encouraged to prevent sexually transmitted diseases. If
      pregnancy is confirmed, prenatal care must be implemented as soon as possible in
      order to minimize the risks of complication and to allow for an effective
      multidisciplinary approach.

PMID- 14676881
TI  - [Endocrine problems in adolescence]
AB  - OBJECTIVE: To present and discuss clinical aspects concerning the most frequent
      endocrine diseases in adolescents and their effects on physical and
      psychoaffective fields in affected patients. METHODS: Review of national and
      international literature combined with the authors own experience with the aim of
      proposing some guidelines for the management of endocrine diseases in
      adolescents. RESULTS: The physical and psychological impacts of these diseases on
      adolescents health may have different intensity. Diabetes mellitus as a chronic,
      self-limiting disease, with increased risk of late complications, is analyzed in
      more detail. Thyroid diseases and gynecomastia usually have a milder evolution,
      but may cause suffering and low self-esteem. CONCLUSIONS: The repercussion of
      these diseases, especially diabetes mellitus and gynecomastia, on the sexuality
      of adolescents should be taken into consideration.

PMID- 14676882
TI  - [Sexually transmitted diseases, AIDS, and use/abuse of psychoactive substances in
      adolescence]
AB  - OBJECTIVE: To discuss theoretical and practical aspects of sexually transmitted
      diseases, AIDS, and psychoactive substances in adolescence, focusing on a
      holistic and multiprofessional approach. METHODS: Review of national and
      international literature on concepts, classifications, social and cultural,
      clinical, therapeutic and preventive aspects of sexually transmitted
      diseases/AIDS, as well as the use of psychoactive substances, with the aim of
      pointing out problem-solving alternatives. RESULTS: Adolescents do not show
      resilient behavior and are vulnerable to environmental hazards. For this reason,
      preventive actions and intervention for the control of sexually transmitted
      diseases/AIDS and use or abuse of psychoactive substances among adolescents are a
      priority. According to the World Health Organization, one out of 20 adolescents
      acquires sexually transmitted disease in the world every year and, more than
      7,000 are infected by HIV every day, totaling 2.6 millions a year. This scenario
      results from unprotected sex and from the interaction between sexually
      transmitted diseases and psychoactive substances, especially alcohol.
      CONCLUSIONS: It is crucial that health care providers consider magnitude,
      transcendence, vulnerability and feasibility as well as the set of interactions
      among substance, individual, and his/her social and cultural environment when the
      multifocal and holistic approach is used. This requires the formation of a
      support and protection network, involving the family, physicians, community, and
      adolescents. The major element in this network, though, are the adolescent
      themselves, who can overcome their conflicts, aiming at a healthy and longer
      life.

PMID- 14676883
TI  - [Neurology in adolescence]
AB  - OBJECTIVE: To provide pediatricians with updated information about the
      neurological problems that most frequently affect adolescents, allowing doctors
      to diagnose, investigate and treat migraine headaches and seizures, and other
      conditions. METHODS: Non-systematic review of medical literature combined with
      clinical experience acquired at the Martagao Gesteira Institute of Child Care and
      Pediatrics, Universidade Federal do Rio de Janeiro. RESULTS: Neurological
      conditions account for an increased frequency of medical appointments among
      adolescents. A significant number of these patients have seizures, and behavioral
      and learning disorders. CONCLUSIONS: Most cases can be assessed by non
      specialists. This articles aims at supplying pediatricians with tools that will
      help them diagnose and treat a great number of the situations.

PMID- 14676884
TI  - [Sexuality in adolescence: development, experience, and proposals for
      intervention]
AB  - OBJECTIVE: To present a literature review of some aspects concerning the
      development of sexuality in the period between childhood and adolescence, and to
      work on some proposals for prevention and intervention. METHODS: Review of
      literature on relevant issues related to the process of psychosocial and sexual
      development during childhood and adolescence, and to the importance of prevention
      education. RESULTS: Differently from genitality, which is only concerned with
      biological aspects, sexuality encompasses emotional aspects, life history and
      cultural values. These factors contribute to the formation of general identity
      and to the components of sexual identity: gender identity, gender role, and
      sexual orientation. Psychosocial and sexual development, emotional balance, and
      social relations are based on sexual experience during childhood and adolescence.
      During adolescence, the relationship with family and social group go through
      marked changes: conflicts arise, and experimentation and risk behavior are
      enhanced. The family, school, and health systems represent important links of
      identification, support, and protection for children and adolescents before they
      reach maturity. CONCLUSIONS: Sexuality education, either individually or in
      group, allows adolescents to experience sexuality and their emotional relations
      in a satisfactory, creative, and risk-free manner, combined with mutual respect
      and absence of gender discrimination.

PMID- 14676885
TI  - [Common orthopedic problems in adolescents]
AB  - OBJECTIVE: Orthopedic problems in children and adolescents are quite frequent.
      For that reason, our aim was to give a remarkable insight into five selected
      topics: spinal deformities, osteochondritis, growing pains, back pain, and
      corrective shoes. METHODS: We analyzed general concepts of spinal deformities,
      including the general definition of scoliosis and its etiologic classification.
      We also discussed the definition, etiology, diagnosis, and treatment of
      osteochondritis, growing pains, back pain, and corrective shoes. The data were
      obtained from review articles, textbooks, and from the Internet. RESULTS: We
      describe the epidemiology, diagnosis, and treatment of the selected conditions
      through review of literature and the authors own experience. CONCLUSIONS:
      Comments and relevant aspects concerning general pediatric practice are
      discussed.

PMID- 14676886
TI  - [Rheumatic diseases in adolescence]
AB  - OBJECTIVE: To present an updated review concerning the most prevalent diseases
      with musculoskeletal signs and symptoms that make adolescents seek medical care,
      giving special emphasis to rheumatic diseases. Our aim is to offer physicians and
      health care providers the possibility of distinct differential diagnoses, thus
      allowing them to establish a therapeutic approach and, if necessary, refer the
      patient to a specialist METHODS: Review of literature using Medline database,
      data obtained at our department, and the authors personal experience. RESULTS:
      Musculoskeletal pain is characteristic of several diseases and usually urges
      adolescents to seek medical care. Rheumatic diseases, especially rheumatic fever,
      account for nearly fifty percent of the cases. In adolescents, it is also
      important that the aspects regarding the diagnosis and treatment of idiopathic
      juvenile arthritis, arthritis associated with enthesitis, systemic lupus
      erythematosus, and vasculitis be considered. Fibromyalgia, reflex sympathetic
      dystrophy, growing pains, hypermobility syndrome, and psychogenic rheumatism are
      noninflammatory conditions that frequently mimic rheumatic diseases. CONCLUSIONS:
      Inflammatory and noninflammatory conditions, and diseases of different etiology
      (infectious, neoplastic, and orthopedic) are frequently associated with
      musculoskeletal pain. It is important that health professionals diagnose these
      diseases as early as possible so that prompt action can be taken and prognosis
      can be improved.

PMID- 14676887
TI  - [Evidence-based Neonatology]

PMID- 14676888
TI  - [Surfactant replacement therapy]
AB  - OBJECTIVE: To analyze and update information about surfactant therapy replacement
      in newborns with lung diseases. SOURCES: Literature review, including textbooks,
      meta-analyses, prospective, randomized controlled trials, retrospective
      assessments and case studies. Literature was reviewed based on the authors
      clinical and scientific experience regarding surfactant replacement therapy in
      neonatal lung diseases. SUMMARY OF THE FINDINGS: Surfactant replacement therapy
      for the neonatal respiratory distress syndrome improves respiratory function, and
      reduces the need for oxygen supplementation and pressure support ventilation, in
      addition to minimizing the air leak syndrome. However, the use of surfactant did
      not prevent the occurrence of other intercurrent diseases such as patent ductus
      arteriosus, intraventricular hemorrhage, necrotizing enterocolitis, retinopathy
      of prematurity, and bronchopulmonary dysplasia. The surfactant treatment
      decreased neonatal mortality up to 40%. The effectiveness of exogenous surfactant
      on other respiratory diseases with surface film dysfunction, such as meconium
      aspiration syndrome, pneumonia, acute respiratory distress syndrome and
      congenital diaphragmatic hernia has not yet been widely accepted. CONCLUSIONS:
      Surfactant replacement is now considered the standard treatment for newborns with
      respiratory distress syndrome. We hope that, in the future, new synthetic
      surfactant preparations will be more effective in treating other infant
      respiratory diseases.

PMID- 14676889
TI  - [Treatment of persistent pulmonary hypertension of the newborn]
AB  - OBJECTIVE: To review the medical literature, emphasizing the new scientific
      advances in the treatment of persistent pulmonary hypertension of the newborn.
      SOURCES: Literature review using Medline and Cochrane library. SUMMARY OF THE
      FINDINGS: Persistent pulmonary hypertension of the newborn (PPHN) is
      characterized by an increase in pulmonary vascular resistance associated with
      right to left shunt through the foramen ovale or ductus arteriosus, leading to
      marked hypoxemia and respiratory failure. The balance between the vasoconstrictor
      (endothelin) and vasodilator (nitric oxide and prostaglandin I2) mediators plays
      an important role in the regulation of the transition from fetal circulation with
      high pulmonary vascular resistance to postnatal circulation with low pulmonary
      vascular resistance. In addition to general management, cardiovascular support,
      the treatment of the cause of the PPHN, and the use of selective pulmonary
      vasodilator such as inhaled nitric oxide (iNO) are indicated. Furthermore, the
      combined therapy with iNO and high-frequency oscillatory ventilation
      significantly improved the oxygenation of patients who were refractory to iNO
      therapy and conventional ventilation. The practice of hyperventilation and the
      administration of nonspecific pulmonary vasodilators (tolazoline) should be
      avoided. On the other hand, the administration of surfactant to patients with
      PPHN due to meconium aspiration should be considered. However, if all these
      therapies fail, extracorporeal membrane oxygenation (ECMO) should be considered
      as rescue therapy. CONCLUSIONS: The mortality due to PPHN has significantly
      decreased with the use of new therapies, and the major concern today is the
      quality of life of these patients, especially in terms of neuropsychomotor
      development.

PMID- 14676890
TI  - [Critical analysis of the use of corticosteroids in the neonatal period]
AB  - OBJECTIVE: To review the use of corticosteroids in the treatment of newborns with
      chronic lung disease, adrenal insufficiency and upper airway edema. SOURCES:
      Review of the available medical literature on the use of corticosteroids in
      newborns. SUMMARY OF THE FINDINGS: Although there is evidence of short-term
      clinical improvement of chronic lung disease with the administration of
      dexamethasone, the available literature did not show significant reduction in
      neonatal morbidity and mortality associated with this condition. CONCLUSIONS: The
      use of corticosteroids must be carefully analyzed and restricted to the treatment
      of severe cases, since these drugs may produce irreversible effects on the
      nervous system and neurological development of newborns.

PMID- 14676891
TI  - [Nutrition of the preterm infants]
AB  - OBJECTIVE: To review the recent medical literature on nutrition of preterm
      infants, focusing on practical aspects that are relevant to pediatricians and
      neonatologists. SOURCES: An extensive review of the related literature using
      Medline, Cochrane Database of Systematic Reviews and Best Evidence was performed.
      SUMMARY OF THE FINDINGS: There is compelling evidence that early nutritional
      practices may affect short-term growth and developmental outcome in preterm
      infants. In addition, these practices have a determinant role in adult health. We
      still have to learn a lot about the safety and effectiveness of nutrient
      administration in preterm infants; about techniques targeted at assessing the
      effect of different nutritional strategies; and about the long term effects of
      these regimens on developmental outcome, growth and disease. CONCLUSIONS: Despite
      recent advances in neonatal nutrition, basic and clinical research is still
      necessary so that the nutritional needs of preterm infants can be better defined
      and adequately provided.

PMID- 14676892
TI  - [Controversies in neonatal resuscitation]
AB  - OBJECTIVE: To describe the main controversies surrounding newborn resuscitation
      procedures. SOURCES: Systematic review of articles from MEDLINE, LILACS and
      Cochrane Library, and of abstracts published in Pediatric Research, using the
      keywords resuscitation, asphyxia neonatorum, and newborn infant. SUMMARY OF THE
      FINDINGS: The effectiveness of hypothermia and ambient air ventilation has been
      under study. The reduction of barotrauma and volutrauma in the ventilation of
      preterm infants is still a challenge. The indication of endotracheal intubation
      in preterm infants based only on their extremely low weight is not a general
      agreement, except if the use of exogenous surfactant is required. There is still
      some uncertainty about the ideal dosage of intravenous or endotracheal adrenaline
      and the need of sodium bicarbonate, mainly in preterm infants. The ethical
      dilemma includes the decision on whether or not resuscitation should be used in
      circumstances related to gestational age, birth weight and severe congenital
      anomalies. CONCLUSIONS: Only the results obtained through animal experiments and
      randomized controlled clinical trials, with a follow-up of the development of
      newborn infants submitted to certain resuscitation procedures, will allow
      changing currently used therapies.

PMID- 14676893
TI  - [Critical analysis of pathophysiological, diagnostic and therapeutic aspects of
      metabolic bone disease in very low birth weight infants]
AB  - OBJECTIVE: To perform a systematic review on the pathophysiology, diagnosis and
      approach of metabolic bone disease in very low birth weight infants. SOURCES:
      Literature review of articles published in Medline within the last twenty years.
      SUMMARY OF THE FINDINGS: The higher survival of very low birth weight infants was
      concurrent with the increased incidence of metabolic bone disease. The process of
      bone mineral acquisition suffers some alterations during the neonatal period,
      including low bone mineral content at birth, insufficient mineral supply in the
      neonatal period, and regulatory disorders, which may compromise growth and
      development on the long run. The diagnosis is based on the association of risk
      factors, and biochemical and radiological alterations. The early intervention in
      the neonatal period prevents the development of severe metabolic bone disease,
      reducing complications during the first year of life. CONCLUSIONS: The early
      diagnosis of metabolic bone disease allows for early intervention, thus
      preventing complications that may originate from the alterations in bone mineral
      acquisition.

PMID- 14676894
TI  - [Hypoxic-ischemic syndrome]
AB  - OBJECTIVE: To review the literature on the hypoxic-ischemic syndrome, emphasizing
      its physiopathology, clinical manifestations, and treatment. SOURCES: Electronic
      search in the Medline and LILACS databases, with selection of the most relevant
      articles. SUMMARY OF THE FINDINGS: The hypoxic-ischemic syndrome is a multisystem
      disease with generalized manifestations. The physiopathology is based on hypoxic
      ischemic brain injury and reperfusion with cellular injury caused by failure of
      ATP production secondary to ischemia, and overproduction of oxidative substances
      caused by reperfusion. Neurological, cardiovascular, respiratory, metabolic,
      gastrointestinal, renal, and hematological manifestations are frequent.
      Multisystem clinical management is complex; the neuroprotective approach is still
      experimental; and the prognosis is not good for those patients with severe
      hypoxic-ischemic encephalopathy. CONCLUSIONS: The management of the hypoxic
      ischemic syndrome is a great challenge to pediatricians., since treatment
      requires multisystem intervention.

PMID- 14676895
TI  - [Treatment of neonatal hyperbilirubinemia]
AB  - OBJECTIVE: To review the recent medical literature on the treatment of neonatal
      jaundice, focusing on practical aspects that are relevant to pediatricians and
      neonatologists. SOURCES: An extensive review of the related literature was
      performed, also including the authors clinical experience in this field of
      investigation. SUMMARY OF THE FINDINGS: Jaundice is very common among infants
      during the first days of life. Several factors such as maternal and neonatal
      history have to be considered before implementing treatment. Significant advances
      have been made in the past few years concerning the treatment of jaundiced
      newborn infants. This review focuses on three forms of treatment of neonatal
      hyperbilirubinemia: phototherapy, exchange transfusion and the use of drugs to
      reduce serum bilirubin concentration. CONCLUSIONS: Nowadays, the in-depth
      knowledge about the mechanism of action of phototherapy, the development of
      intensified phototherapy units and the use of drugs to reduce bilirubin
      formation, have contributed to significantly decrease the need for exchange
      transfusion.

PMID- 14676896
TI  - [Neonatal nosocomial infections]
AB  - OBJECTIVE: To review the current medical literature on neonatal nosocomial
      infections, emphasizing aspects of neonatal colonization, immune system and
      infection mechanisms, modes of transmission, epidemiology, surveillance and
      prevention of these infections, in addition to assessing peculiarities about
      etiologic agents and prophylactic recommendations. SOURCES: Electronic search in
      the Medline and LILACS databases, with selection of the most relevant articles
      published within the last ten years. SUMMARY OF THE FINDINGS: The several
      peculiarities that cause greater susceptibility to infection in newborns, and the
      survival of preterm infants due to the invasive procedures and treatment with
      broad spectrum antibiotics at intensive care units are responsible for prevalence
      rates of neonatal nosocomial infections between 9.3 and 25.6%. Neonatal
      nosocomial infections affect at least 50% of newborns who weigh less than 1500 g,
      which ends up increasing mortality rates. Full-term newborns frequently have skin
      and soft tissue lesions caused by gram-positive organisms. In neonatal intensive
      care units, sepsis and pneumonia are frequently diagnosed (especially those
      caused by S. aureus, S. epidermidis, E. coli, K. pneumoniae, and E. cloacae). An
      increasing frequency of resistance to several antimicrobial drugs has been
      observed. A nosocomial infection surveillance program tailored to the
      characteristics of the neonatal unit allows the identification of infection
      outbreaks, the rational use of antibiotics and the application of preventive
      measures. CONCLUSIONS: Neonatal nosocomial infections are a relevant problem.
      Their control can only be achieved if adequate measures concerning pregnant
      women, hospital environment, nursing staff, and newborns are adopted. Although
      new prophylactic measures are being proposed for preterm infants, they are costly
      and do not preclude continued epidemiological surveillance and control in
      neonatal units.

PMID- 14676897
TI  - [Neonatal apnea]
AB  - OBJECTIVE: To review medical literature related to apnea of prematurity. SOURCES:
      Extensive literature search and clinical practice-oriented concepts. SUMMARY OF
      THE FINDINGS: Apnea is one of the most common respiratory disorders in the
      neonatal period. Immaturity of the central nervous system is associated with
      instability of respiration. Therefore, apnea manifests itself in other systems,
      causing problems such as hypoglycemia, hypothermia, infection, or patent ductus
      arteriosus. Apnea may be central, obstructive or mixed depending on the presence
      of air flow through the upper airways. Diagnosis should involve careful
      observation by unit personnel and the monitoring of heart rate, respiratory
      frequency or arterial oxygen saturation. Initially, the treatment consists of
      xanthines (caffeine and aminophylline). If respiratory failure occurs, then
      continuous positive airway pressure (CPAP), and mechanical ventilation should be
      used. CONCLUSIONS: Preterm newborns are susceptible to respiratory problems,
      having apnea as a clinical manifestation of disorders in many organs and systems.

PMID- 14676898
TI  - [Use of blood and blood components and derivatives in newborn infants]
AB  - OBJECTIVE: To describe the current rationale for the transfusion of blood, blood
      components, and plasma derivatives in term and preterm infants. SOURCES:
      Selection of relevant medical articles published within the last ten years.
      SUMMARY OF THE FINDINGS: Peculiar characteristics and special care concerning
      exchange transfusion, transfusion of red blood cells, platelets, granulocytes,
      and fresh frozen plasma were described. The recommendations for the use of
      hematopoietic growth factors, and plasma derivatives such as fibronectin,
      immunoglobulins, and albumin were also evaluated. CONCLUSIONS: The authors
      comment on the recommendations and contraindication of blood transfusions, and
      warn against the limitations and hazards involved.

PMID- 14676900
TI  - [An update on infant nutrition]

PMID- 14676899
TI  - [Seizures in the neonatal period]
AB  - OBJECTIVE: To characterize and differentiate neonatal seizures from those that
      occur at different ages, based on a critical assessment of the available
      literature and also on the authors clinical experience. SOURCES: Literature
      review, including up-to-date and classical studies that helped us to better
      understand clinical, neurophysiological and physiopathological aspects related to
      seizures in the newborn. SUMMARY OF THE FINDINGS: The authors present clinical
      and electroencephalographic characteristics of neonatal seizures, discuss their
      classification, treatment and prognosis. CONCLUSIONS: Neonatal seizures have a
      distinct clinical pattern, which justifies the necessity of an appropriate
      classification. The etiology is predominantly symptomatic and multifactorial; the
      treatment should follow a routine protocol, and the prognosis seems to be closely
      related to etiology.

PMID- 14676901
TI  - [Development children's eating behavior]
AB  - OBJECTIVES: Review the literature, exploring factors that contribute to the
      development of children's eating behavior such as the role of learning and social
      context. METHODS: The review of the literature was done using Medline, Psyclit,
      and Lilacs as resources for assessing international and national research
      articles on child nutrition, with an emphasis on children's eating behavior.
      These articles were revised and grouped together according to the topic. RESULTS:
      Family is responsible for the development of children's eating behavior through
      social learning. Parents are children's first nutritional educators. Children's
      eating experiences are influenced by cultural and psychosocial factors. Social
      context plays a relevant role in this process, especially through the strategies
      used by parents to encourage children to have a balanced diet and to eat specific
      foods. These strategies may contain adequate and inadequate stimuli as to the
      development of children's food preference and food intake self-control.
      CONCLUSION: The learning process is a determining factor for children's eating
      behavior, and is associated with three factors: food flavor conditioning, food
      postingestional consequences, and social context. Parents are deeply concerned
      with the amount of food their children eat and not with the development of more
      adequate habits and attitudes related to dietary quality.

PMID- 14676902
TI  - [Breast-feeding in clinical practice]
AB  - OBJECTIVE: To present an updated review on practical aspects of breast-feeding
      promotion and management. METHODS: Review of relevant publications from
      scientific journals, technical books and publications by international
      organizations. RESULTS: Nowadays, exclusive breast-feeding is recommended for a
      period of approximately 6 months, and maintenance of complementary breast-feeding
      should continue for 2 or more years. Despite abundant scientific evidence on the
      superiority of breastmilk over other types of milk, the number of women who
      breast-feed their infants according to present recommendations is still low.
      Health care providers can improve this scenario by encouraging breast-feeding and
      helping nurturing mothers to overcome breast-feeding hindrances. Therefore,
      health professionals must have the necessary knowledge and skills for managing
      the different stages of lactation. This way, they will be able to provide
      prenatal counseling, guidance and help during the breast-feeding initiation
      period, careful evaluation of breast-feeding techniques and adequate
      interventions in the event of any problems associated with breast-feeding. This
      article is concerned with some important topics related to breast-feeding in
      clinical practice. CONCLUSION: Breast-feeding is the ideal method for infant
      feeding, and it can certainly be facilitated by health care providers through
      adequate clinical practice.

PMID- 14676903
TI  - [Complementary feeding]
AB  - OBJECTIVE: To present an updated review about complementary feeding in infants
      and children under 2 years old. METHODS: Relevant materials from scientific
      journals, technical books and publications by international organizations were
      used. The most important source of data was a publication by the World Health
      Organization on complementary feeding carried out in Montpellier, France, in
      December 1995. RESULTS: In recent years, new findings on ideal infant feeding
      have buried former concepts and practices. The value of exclusive breast-feeding
      during the first months of life and the introduction of timely and adequate
      complementary feeding has been acknowledged. Complementary foods are defined as
      any solid or liquid foods with nutritional value other than breastmilk, offered
      to breast-fed infants It is recommended that complementary feeding be initiated
      around the 6th month of life. These foods should be rich in energy, proteins and
      micronutrients, free from contamination, easily digestible and in adequate
      amount. On recommending a healthy diet, the availability, accessibility and
      cultural values of food should be taken into consideration. CONCLUSION: Health
      professionals have an important role in the improvement of infant nutrition.
      Those in charge of child care have to be properly advised and warned of the
      importance of a healthy diet for current and future health status.

PMID- 14676904
TI  - [Nutrition in adolescence]
AB  - OBJECTIVE: To emphasize the importance of nutrition for healthy growth and
      development during adolescence. METHODS: 1 - National and international
      bibliographic review of the main anthropometric data to be used during puberty. 2
      - Description of practical questions for the evaluation of the nutritional status
      of adolescents. 3 - Main interventions and prevention activities for nutritional
      and health risk situations to be planned by the pediatrician in his professional
      activities with the multidisciplinary team. RESULTS: Adolescence is a life period
      between 10 and 20 years of age, marked by intense body changes resulting from
      puberty and psychosocial development that influence nutritional requirements. The
      routine follow-up of adolescents should include the evaluation of growth velocity
      and sexual maturation, and also the anthropometric measures for the evaluation of
      the nutritional status. During the pubertal growth spurt, there is an increase in
      the protein, calorie, and nutrient requirements, in addition to the extras
      recommended for growth and for several activities, according to different life
      styles. CONCLUSIONS: Dealing with adolescents consists of opening new
      opportunities for nutritional counseling and health education. The dissemination
      of healthy eating concepts is one of the basic recommendations concerning
      community and clinical intervention. It is also one of the pediatrician s
      obligations towards adolescents.

PMID- 14676905
TI  - [Diagnosis of child and adolescent nutritional status]
AB  - OBJECTIVE: To present a review on the methods for the assessment of child and
      adolescent nutritional status, emphasizing anthropometry and the various methods
      for the assessment of body composition; pointing out their advantages,
      limitations and risks. METHODS: Chapters of textbooks, theses, and articles
      relevant to the topic, as well as personal files and authors previous
      publications were selected. RESULTS: Anthropometry, which consists of the
      assessment of physical dimensions and global composition of the human body, has
      been regarded as the most frequently used isolated method for nutritional
      diagnosis, especially in childhood and adolescence, due to its ease of use, low
      cost and innocuousness. The most frequently adopted measurements aim at
      determining body mass, expressed by weight; linear dimensions, especially height;
      body composition and reserves of energy and proteins, estimated through
      subcutaneous fat and muscle mass. Laboratorial methods especially developed for
      the assessment of body composition are presented here. The justification for the
      use of methods that expose children and adolescents to ionizing radiation is also
      presented. CONCLUSIONS: On defining methods for the assessment of nutritional
      status, we should select those that better detect the nutritional deficiencies we
      want to correct, also taking into consideration their costs, level of personal
      skill required for their proper application, necessary time for application,
      acceptability by the studied population and possible health risks.

PMID- 14676906
TI  - [Malnutrition: a secular challenge to child nutrition]
AB  - OBJECTIVE: To review current knowledge about child malnutrition, including the
      historical aspects of the problem, its dimension as a childhood public health
      problem, its natural history, physiopathology, clinical features, diagnosis and
      treatment, and strategies used by the health sector to control this disease.
      METHODS: Information was collected by researching the Medline system, the Bireme
      library, internet sites of interest, catalogues of publications produced by
      Brazilian governmental organizations and international institutions dealing with
      child nutrition. RESULTS: The review pointed out that despite recent world
      prevalence reduction, child malnutrition is a major public health problem in
      developing countries. Malnutrition, in any of its forms, contributes for more
      than 50% of deaths among children under 5 years in those countries. Mortality
      rates of severely malnourished children treated as in patients have been
      unchanged for the last five decades. Guidelines for improving the treatment and
      reducing mortality rates of severely malnourished children treated in hospitals
      were recently defined by the World Health Organization. Even though some positive
      results have been achieved by the health sector in reducing child malnutrition
      prevalence, the effectivity of the interventions is often low. Lack of food might
      limit the success in treating and preventing malnutrition. Factors that may
      contribute to the effectiveness of interventions against malnutrition include
      approaches which reassure the confidence of health professionals about achieving
      positive results with the proper treatment of malnourished children,
      establishment of an effective relationship between health professionals and
      mothers, as well as practical support to mothers in recognizing them as valuable
      active agents for their children nutrition rehabilitation at the household level.
      CONCLUSIONS: Throughout the centuries, malnutrition has been the biggest
      challenge faced by developing countries in order to guarantee to children under
      five years of age their right of being well nourished and healthy. The current
      challenge is the proper use of the available scientific knowledge on child
      nutrition to further reduce the figures for all the types of child malnutrition.

PMID- 14676907
TI  - [Iron deficiency anemia in children]
AB  - OBJECTIVE: To present the aspects involved in iron deficiency anemia in children
      and several measures for its control. METHOD: The authors performed an extensive
      review of national and international literature and associated findings to their
      own personal experience in this area. The study included general aspects of iron
      metabolism, iron deficiency, and the mechanisms that trigger iron deficiency
      anemia (IDA). In addition, the authors focused on the current situation of IDA in
      Brazil, its prevention and treatment. RESULTS: Iron deficiency is still one of
      the most serious public health issues in Brazil despite all the available
      knowledge about intervention measures. The studies found in the literature show
      excellent results through the fortification of foods and/or iron supplementation,
      in association with nutritional education. CONCLUSION: The authors concluded that
      Brazil detains sufficient knowledge regarding IDA, and that the proposed
      intervention measures have proved to be efficient. There is, however, a lack of
      political will and focus at all governmental levels (Federal, State and
      Municipal), and a greater commitment on the part of health professionals that
      allow the alarming prevalence rates of iron deficiency anemia in our population
      at higher risk (i.e. children) to be reversed.

PMID- 14676908
TI  - [Childhood and adolescent obesity]
AB  - OBJECTIVE: To review the medical literature in the last 5 years regarding obesity
      in children as well as its treatment. METHODS: Literature review. RESULTS:
      Obesity is a chronic disease that presents high percentages of therapeutic
      failure and recurrence, leading to serious physical and psychological
      consequences, especially in its most severe forms. Health care professionals and
      families usually neglect the treatment of obesity in the hope of a spontaneous
      reversal of the condition during adolescence. There is a great probability that
      obese children and adolescents will continue to be obese in adulthood, thus
      increasing morbidity and mortality of several diseases. CONCLUSION: Pediatricians
      are supposed to early identify children at greater risk for obesity, taking
      effective control measures in order to achieve a more favorable prognosis.

PMID- 14676909
TI  - [Vitamin A deficiency and xerophtalmia]
AB  - OBJECTIVE: To review cases of vitamin A deficiency and the effects of vitamin A
      supplementation on child morbidity and mortality. METHODS: Articles published in
      scientific journals, technical and scientific books, and also publications by
      international organizations were used as source of information. RESULTS: Clinical
      manifestations of xerophthalmia affect the retina (night blindness), the
      conjunctiva (conjunctival xerosis, with or without Bitot spots), and the cornea
      (corneal xerosis). Corneal xerosis may lead to corneal ulceration and
      liquefactive necrosis (keratomalacia). A priori, these signs and symptoms are the
      best indicators of vitamin A deficiency; they are, however, extremely rare.
      Laboratory indicators include Conjunctival Impression Cytology and serum retinol
      concentrations. The World Health Organization (WHO) recommends the use of two
      biological markers in order to characterize vitamin A deficiency in a given
      population. If only one biological marker is used, this marker has to be backed
      up by a set of at least four additional risk factors. Corneal xerophthalmia
      should be treated as a medical emergency; In the event of suspected vitamin A
      deficiency, a 200,000 IU vitamin A dose should be administered orally, repeating
      the dose after 24 hours (half the dose for infants younger than one year).
      Vitamin A supplementation in endemic areas may cause a 23 to 30% reduction in the
      mortality rate of children aged between 6 months and five years, and attenuate
      the severity of diarrhea. The methods for the control of vitamin A deficiency are
      available in the short (supplementation with megadoses), medium (food
      fortification), and long run (diet diversification). CONCLUSION: There is
      evidence of vitamin A deficiency among Brazilian children. Pediatricians must be
      aware of the signs and symptoms of this disease, however sporadic they might be.
      It is of paramount importance that vitamin A be included in public policy plans
      so that we can ensure the survival of children.

PMID- 14676910
TI  - [Adolescent-onset anorexia nervosa]
AB  - OBJECTIVE: This paper is a review on the topic of adolescent-onset anorexia
      nervosa. According to the literature, this disorder presents high morbidity and
      mortality, with increasing incidence over the last decades, thus enhancing the
      importance of scientific investigation on the subject. METHODS: The authors
      performed a non-systematic review of the related literature and also reported
      their clinical experience. RESULTS: Age and gender are important risk factors.
      The peak of incidence occurs in adolescence and the prevalence is 9 times higher
      in females. It was initially believed that anorexia nervosa manifested itself
      only in higher socioeconomic levels, which are more highly exposed to the demands
      of western beauty standards. More recent studies have identified similar
      incidence of this disorder also in lower socioeconomic levels, rural areas and
      Asian communities. The clinical features are: refusal to maintain weight at or
      above a minimal normal weight for age; high, intense fear of gaining weight or
      becoming fat, even though underweight; disturbance in the way of experiencing one
      s body weight or shape, and amenorrhea. The most common physical complications
      are similar to those of chronic malnutrition and depression is the main
      comorbidity. CONCLUSIONS: Treatment should be multidisciplinary, taking into
      account the plurality of etiological factors. Family therapy plays an important
      role, particularly when this disorder manifests itself during adolescence.

PMID- 14676911
TI  - [Basis of nutritional support in pediatrics]
AB  - OBJECTIVE: To present an update and systematic review of the basis of nutritional
      support in pediatrics, emphasizing the importance of nutrition in critically ill
      patient. METHODS: Relevant studies were selected from databases (Medline, Scielo,
      Lilacs, etc.). Textbooks and theses were analyzed, and the authors personal
      experience was also considered. RESULTS: Nutritional therapy is part of the
      treatment. In order to reach the objective, it is important to determine specific
      nutritional requirements of water, calories, proteins, macro and micronutrients.
      So, nutritional evaluation should consist of clinical, anthropometric, and
      laboratory assessment, so that the best nutritional therapy (parenteral and/or
      enteral) is chosen. Patient monitoring is also indicated in order to prevent
      complications. CONCLUSION: Nutritional therapy is essential for the treatment.
      When well indicated and well monitored, it helps in the patient s recovery, and
      in the decrease of morbidity and mortality.

PMID- 14676912
TI  - [Parenteral nutrition in pediatrics]
AB  - OBJECTIVE: To present a review on parenteral nutrition in infants and children,
      characterizing the importance of nutrition therapy to support and recover their
      nutritional status. METHODS: Articles from specific journals were analyzed.
      Information was also obtained from the author s own experience in the area.
      RESULTS: Major recommendations; venous access; protein-energy composition
      (electrolyte, vitamins and trace elements); formulation; administration; clinical
      and laboratorial control; and complications were also discussed. CONCLUSIONS:
      Parenteral nutrition, if well-indicated, is very important for the management of
      several childhood diseases, allowing the maintenance and restoration of
      nutritional status

PMID- 14676913
TI  - [Nutrition and physical activity]
AB  - OBJECTIVE: To review data about the nutrition of physically active children and
      adolescents. METHOD: Review of literature using MEDLINE and LILACS data base and
      the keywords sport or physical activity and nutrition and children or
      adolescents. RESULTS AND CONCLUSION: Involvement of children and adolescents in
      sports activities is important for their growth and development process, which
      should be regularly assessed. Na adequate diet should provide enough energy and
      nutrients so that young athletes can meet their requirements. The diet should
      suit the different stages of training, before, during and after competition.
      Hydration should be planned carefully as children present a less efficient
      thermoregulation than adults and can dehydrate more quickly, specially during
      sports practice. Female athletes can present menstrual alterations and inadequate
      bone growth due to excessive training associated with inadequate energy intake.
      Eating disorders are found among some groups of athletes. Physical activity
      should be encouraged as part of the treatment of overweight children.

PMID- 14676914
TI  - [Pediatric gastroenterology: past and future challenges]

PMID- 14676915
TI  - [Persistent diarrhea]
AB  - INTRODUCTION: Persistent diarrhea has high impact on infantile morbidity and
      mortality rates in developing countries. Several studies have shown that 3 to 20%
      of acute diarrheal episodes in children under 5 years of age become persistent.
      DEFINITION: Persistent diarrhea is defined as an episode that lasts more than 14
      days. ETIOLOGY: The most important agents isolated in persistent diarrhea are:
      Enteropathogenic E. coli (EPEC), Salmonella, Enteroaggregative E. coli (EAEC),
      Klebisiella and Cryptosporidium. CLINICAL ASPECTS: In general, the clinical
      characteristics of patients with persistent diarrhea do not change with the
      pathogenic agent. Persistent diarrhea seems to represent the final result of a
      several insults a infant suffers that predisposes to a more severe episode of
      diarrhea due to a combination of host factors and high rates of enviromental
      contamination. Therefore, efforts should be made to promptly treat all episodes
      of diarrhea with apropriate follow-up. THERAPY: The aim of the treatment is to
      restore hydroelectrolytic deficits and to replace losses until the diarrheal
      ceases. It is possible in the majority of the cases, using oral rehydration
      therapy and erly an appropriate type of diet. PREVENTION: It is imperative that
      management strategies also focus on preventive aspects. The most effective
      diarrheal prevention strategy in young infants worldwide is promotion of
      exclusive breast feeding.

PMID- 14676916
TI  - [Peptic ulcer]
AB  - OBJECTIVE: To present a current review about pathogenesis, pathophysiology,
      diagnosis, and treatment of peptic ulcer disease in children, based on the
      reviewed publications and the author personal experience. METHODS: We revised the
      most relevant articles about peptic ulcer in children, published from the last 20
      years. RESULTS: The gastroduodenal peptic ulcer is very common in adults, mostly
      in the developing countries. Although it is less frequent in children, the
      optical fibroendoscopy has improved the number of diagnosed cases. The peptic
      ulcer is classified as its etiology in primary and secondary. The secondary
      peptic ulcer is related to a subjacent disease or use of drugs, while the primary
      ulcer happens in the absence of underlying systemic diseases The primary duodenal
      ulcer is the most common presentation, and there are strong evidences of the H.
      pylori association in the etiology. Clinical presentation changes with age and
      ulcer type. Secondary ulcers are mostly acute and sometimes dramatic, while the
      primary ones have a chronic evolution mostly similar to patients with functional
      recurrent abdominal pain, but the presence of epigastric pain, feeding-related
      pain, vomiting, bleeding, familiar history for peptic ulcer, nocturnal pain, and
      male gender are strongly related to peptic ulcer. The acid antisecretory agents
      have great efficacy on relieving symptoms and solving ulcerate lesion, although
      the H. pylori eradication itself prevents primary duodenal ulcer recurrence.
      CONCLUSIONS: The primary peptic ulcer involve many factors in Its
      etiopathogenesis, being H. pylori the most important of them Although there isn t
      yet a ideal therapeutic course. The antibiotics play an important role in peptic
      ulcer and the H. pylori research must be done for na accurate diagnosis and
      treatment.

PMID- 14676917
TI  - [Gastrointestinal bleeding]
AB  - OBJECTIVE: To present an analysis of the occurrence of gastrointestinal bleeding
      in children and emphasize: i) diagnostic methods; ii) the organized use of
      different therapeutic approaches in upper gastrointestinal bleeding; iii) the
      review of concepts, classifications and techniques used in endoscopy, which are
      important to the practice of clinical pediatrics. METHODS: Literary review of
      chapters selected from textbooks, pertinent articles obtained through the Medline
      system and active search, as well as personal archives belonging to the authors.
      RESULTS: The differential diagnosis of gastrointestinal bleeding in children
      varies according to the age. The causes of upper gastrointestinal bleeding are
      subdivided into variceal and nonvariceal. Nonselective beta-blockers are
      recommended to prevent variceal bleeding. Vasoactive drugs, such as somatostatin,
      octreotide, and glypressin may be used, showing good results in both variceal and
      nonvariceal acute bleeding. Both sclerotherapy and variceal ligation can be used
      in children to achieve variceal eradication. Cyanoacrylate is effective and
      presents the lowest complication rate related to gastric variceal bleeding. The
      presence of hemorrhage stigmata, such as active bleeding and visible vessel in
      ulcers is indicative of a higher risk for recurrent bleeding, suggesting the need
      for endoscopic hemostasis. Proton pump inhibitors are more efficacious than H2
      receptor antagonists to promote the peptic ulcer healing. CONCLUSION: The correct
      etiologic diagnosis of gastrointestinal bleeding in children is fundamentally
      important to adopt the adequate therapeutic approach, whose main advances concern
      the pharmacological and the endoscopic treatment.

PMID- 14676918
TI  - [Constipation]
AB  - OBJECTIVE: To review current information concerning the importance,
      pathophysiology, clinical presentation, and treatment of chronic constipation in
      Pediatrics. METHODS: Bibliographic review of Medline database and articles
      published by the authors. RESULTS: Constipation is a common disorder in
      childhood. The pathophysiology of constipation involves the interaction of
      several factors: low-fiber diet, early weaning, painful bowel movement, fecal
      retention, disturbance of intestinal motility, and genetic predisposition. The
      clinical presentation of children with constipation is variable. Several patients
      present the onset of constipation during the 1st year of life; however, the
      medical treatment is usually initiated only after a long period. Some patients
      are recognized due to the presence of complications, such as soiling, abdominal
      pain, and urinary abnormalities. The treatment should be adapted to each patient,
      and includes general orientation, complete colonic emptying, maintenance
      treatment, and a behavioral program to regulate bowel habits. Regardless of the
      fact that most children present functional chronic constipation, much attention
      should given to the entities that constitute the differential diagnosis.
      Specialized evaluation and diagnostic techniques should be indicated according to
      the patient s individual characteristics and when the clinical evolution is not
      satisfactory. CONCLUSIONS: The long-term control of chronic constipation depends
      on the acquisition of dietary habits that provide an adequate intake of dietary
      fiber. It is possible that a high-fiber diet is important not only to the control
      of constipation, but may also reduce the risk for diet-related chronic diseases
      during adulthood.

PMID- 14676919
TI  - [Irritable bowel syndrome]
AB  - OBJECTIVE: To review the pathophysiology in order to explain the clinical
      manifestation and treatment of this syndrome, which has not been completely
      explained yet. METHODS: References were searched on recent review articles,
      personal files, and Medline. RESULTS: Irritable bowel syndrome in children or
      chronic nonspecific diarrhea is a very frequent reason for pediatric
      gastroenterology visits. It is a benign disease and disappears with age, but may
      cause extreme worry to parents. The pathophysiology is still unclear, and there
      is not laboratory corroboration. Thus, it is frequently diagnosed incorrectly,
      although it has proper clinical manifestation (if there is no diet or medicine
      manipulation). Dietary advice is usually efficient, and is based on
      pathophysiologic data. The use of drug is still discussed. CONCLUSIONS: Irritable
      bowel syndrome must be always considered in oligosymptomatic children without
      signs of malnutrition, with diarrhea, between 6 months and 5 years of age. Drugs
      are not necessary, and their action is still unclear. Food manipulation based on
      pathophysiology is enough.

PMID- 14676920
TI  - [Recurrent abdominal pain]
AB  - OBJECTIVE: To present current concepts about the diagnosis of recurrent abdominal
      pain and to review the basis of the therapeutic approach for this disease in
      children and adolescents. METHODS: References were obtained from the Medline,
      from recent review articles, and from personal files. Books and dissertations
      were also analyzed. Only the most important articles were included in this
      review. RESULTS: Recurrent abdominal pain is the main cause of recurrent pain in
      children between 4 and 16 years of age. It is defined as the occurrence of three
      or more abdominal pain attacks within 3 months or less. These attacks are severe
      enough to interrupt routine activities, making the child remain asymptomatic
      between the episodes of pain. The diagnosis is based on a detailed clinical
      history, on an improved physical examination, and on a few laboratory tests. It
      can be manifested with isolated paroxysms of umbilical pain, abdominal pain with
      dyspeptic symptoms, and abdominal pain with digestive tract dysfunction. The
      treatment must emphasize the cognitive-behavioral factors of the recurrent pain.
      CONCLUSIONS: The treatment of recurrent abdominal pain using the strategy
      presented here represents an equilibrium in which time is neither wasted nor
      insufficient during the investigative process required for treating children and
      their families with this problem.

PMID- 14676921
TI  - [Inflammatory bowel diseases]
AB  - OBJECTIVE: To present a review about inflammatory bowel diseases in childhood so
      that pediatricians become familiar with two diseases (ulcerative colitis and
      Crohn s disease) that are increasing in incidence. METHODS: Articles of specific
      gastroenterological journals were analyzed. Information was also obtained from
      the author s extensive professional experience in the area. RESULTS: The two
      diseases are described. Etiopathogenesis is obscure. Clinical presentation,
      diagnosis, and treatment are discussed, with details and practical aspects to
      enable the pediatrician to promptly understand the subject. CONCLUSIONS: The
      inflammatory bowel disease is a condition of high morbidity, and the pediatrician
      who assists the case must have a very good technical knowledge about the disease,
      and must be very comprehensive and emotionally serene, in order to afford the
      young patient a better quality of life throughout the complicated evolution of
      this disease.

PMID- 14676922
TI  - [Autoimmune hepatitis]
AB  - OBJECTIVE: To review an update of autoimmune hepatitis in children, based on
      classification, diagnostic and therapeutic criteria. METHODS: Articles on the
      theme were selected and updated, and the author's experience at the Liver Unit,
      Children's Hospital, School of Medicine, Universidade de Sao Paulo, was
      considered as well. RESULTS AND CONCLUSIONS: Autoimmune hepatitis has clinical
      features suggestive of acute viral hepatitis; however, other clinical features,
      laboratory tests, endoscopic and histological findings pointed to chronic liver
      disease, and the majority of the cases evolved to hepatic cirrhosis. The
      treatment with corticosteroids and/or azathioprine altered the natural history of
      autoimmune hepatitis, and the survival was 80% in 10 years, although hepatic
      cirrhosis was present at the beginning, without hepatic decompensation.

PMID- 14676923
TI  - [Neonatal cholestasis]
AB  - OBJECTIVE: To warn pediatricians about the early recognition of cholestasis in
      newborns and infants. METHODS: A bibliographic research about cholestasis was
      performed using Medline, and emphasizing the most relevant publications of the
      last 30 years. RESULTS: The concept of cholestasis and the causes of cholestatic
      tendency in newborns and infants are described. Several causes of intra and
      extrahepatic cholestasis are reported as well. In this review, only the diseases
      with diagnostic, therapeutic or prognostic peculiarities are commented, including
      extrahepatic biliary atresia, idiopathic neonatal hepatitis, galactosemia, and
      Alagille s syndrome. Furthermore, several resources are discussed for the
      diagnosis of cholestasis. CONCLUSIONS: The establishment of the diagnosis of
      cholestasis through the detection of hyperbilirubinemia in newborns who present
      jaundice after 14 days of life is a goal that could change the prognosis of
      several diseases responsible for neonatal cholestasis.

PMID- 14676924
TI  - [Liver transplantation]
AB  - OBJECTIVE: To review the clinical aspects and the theoretical basis of liver
      transplantation in children, focusing mainly pre and post surgical periods.
      METHODS: References were obtained from computerized search in the National
      Library of Medicine (Medline), recent review articles, and personal files.
      RESULTS: Great development has occurred in surgical techniques, in organ
      preservation, in postoperative care, and in immunosuppression methods after the
      first liver transplantation surgery took place in a child with biliary atresia in
      1963. Liver transplantation has become an efficient therapy, widely accepted and
      used in all age groups. It is a very complex procedure, with many professionals
      involved and with several legal, ethical and economical implications. We review
      in this article the clinical aspects before transplantation, including
      indications, contraindications, clinical and laboratory evaluations, as well as
      postsurgical aspects, both in the immediate period, after the 1st week, and the
      long-term outcome, discussing the complications and the treatment of each.
      CONCLUSIONS: Liver transplantation has dramatically improved the survival of
      pediatric patients with chronic hepatic diseases. Patients of liver
      transplantation in the pediatric age group present today survival rates of 90% in
      the different transplantation centers.

PMID- 14676925
TI  - [Up-to-date clinical and experimental basis for the use of probiotics]
AB  - OBJECTIVE: To evaluate the potential of probiotics or biotherapeutic agents for
      the prevention and/or treatment of selected intestinal infections. METHODS:
      Medline database was searched for all relevant articles between 1990 and February
      1998. Bibliographies of articles were also used. All animal experiments and
      placebo-controlled human studies were reviewed in order to provide information on
      the mechanisms of action, potential efficacy, or adverse effects of these
      biotherapeutic agents. RESULTS: In the first part of this review, the different
      mechanisms of action that are effective in the treatment of diarrhea were
      discussed, and they were well demonstrated in laboratory animals. The most
      important are: enzymatic induction of disaccharidase activity, trophic effects on
      the intestinal mucosa, action in blocking bacterial toxins, and also induction of
      the immunologic response. Therapeutic effects of probiotics in humans, mainly in
      the gastrointestinal tract, were reported in the second part. Placebo-controlled
      studies have shown that biotherapeutic agents have been used successfully in the
      treatment of acute diarrhea in infants, traveler s diarrhea, antibiotic
      associated diarrhea, with or without Clostridium difficile-associated
      enterocolitis (pseudomembranous colitis), and in immunosuppression-associated
      diarrhea, including AIDS. Lactobacillus, Bifidobacterium and Saccharomyces
      boulardii were the most important biotherapeutic agents to be considered.
      CONCLUSIONS: Currently, there is evidence that the administration of selected
      microorganisms is benefic in the prevention and treatment of certain intestinal
      infections. According to the literature, Saccharomyces boulardii is the most
      important probiotic. Possible future indications were discussed, such as the
      probable synergic effect of many probiotics due to their different and
      complementary mechanisms of action. The importance of new experimental and
      clinical studies for the better understanding of actions and the use of
      probiotics in other clinical situations was emphasized.

PMID- 14676926
TI  - [Gastroesophageal reflux]
AB  - OBJECTIVE: To discuss clinical, diagnostic and therapeutic aspects of
      gastroesophageal reflux. METHOD: We accomplished a literature review of the last
      30 years, by means of Lilacs and Medline databases. RESULTS: The gastroesophageal
      reflux is one of the most frequent causes of medical appointments with pediatric
      gastroenterologists. It represents a benign condition, characterized by
      regurgitations that can be resolved with general measures. Medical management
      with prokinetics and antacid agents controls clinical manifestations and prevents
      complications. Fundoplication is reserved to a minority of cases. COMMENTS: Some
      aspects of the clinical treatment have to be emphasized. Thickened/Solid diet and
      erect posture must be always recommended. Cisapride, the most commonly employed
      prokinetic agent, may prolong ventricular repolarization. Other prokinetic agents
      should be used in children. Bronchospasm or clinical manifestations of
      esophagitis indicate the use of antacid drugs.

PMID- 14676928
TI  - [Schistosomiasis mansoni in Bahia, Brazil: historical trends and control
      measures].
AB  - In order to aid the development of new approaches to schistosomiasis control,
      changes were analyzed in prevalence at the county level in the State of Bahia
      from the 1950s to the 1990s, as were determinants and the effect of community
      based chemotherapy. In general, no substantial changes were observed in the basic
      pattern of spatial distribution of the prevalence of infection. However, during
      the period studied, there was an overall reduction in prevalence from 15.6% to
      9.5% and an increase in prevalence rates in some counties from the western,
      southeastern, and northern areas of Bahia, indicative of new transmission areas.
      The effect of mass chemotherapy was analyzed. In the Paraguacu Basin, where this
      control measure was used on a large scale, there was a reduction in prevalence
      similar to areas where this measure was not used. Correlation and regression
      analysis also failed to show links between mass chemotherapy and long term
      reduction in prevalence. The most powerful variables to explain these changes
      were those related with population dynamics. These findings strongly suggest that
      the reduction in prevalence observed in some areas of the State must be
      attributed to factors related with the spatial organization of this territory,
      causing a general decrease in the transmission rate, secondary to mass
      chemotherapy. At the same time, the incomplete form and the spatial inequalities
      that characterized the urbanization process created favorable conditions for the
      spread of schistosomiasis mansoni and the establishment of new foci.

PMID- 14676929
TI  - In vitro activity of naturally occurring peptides (defensins) against Listeria
      monocytogenes.
AB  - Autoclaved distilled water samples were inoculated with L. monocytogenes strain
      V7 and strain VPH-1, and incubated aerobically, at 30 C for 48 hours. Each strain
      was tested individually, and growth curves were determined at 1, 2, 3, 4, 5, 21,
      24, and 48 hours. The growth or survival of L. monocytogenes was similar for both
      strains, with survivors at 24 hour-incubation. The microbicidal activity of one
      synthetic cationic peptide (NP-2) was examined against L. monocytogenes strain
      V7, in a water system. Antibacterial activity of NP-2 (1, 5, and 10 g/ml) was
      best expressed at 60 minute-incubation, with 10 g/ml of peptide, at 30 C.

PMID- 14676930
TI  - [Citizenship, community participation, and health as seen by health care
      professionals: a case study in public health services].
AB  - This paper deals with the subject of citizenship and people's participation in
      the health area through an analysis of ideas pertaining to a specific group:
      health care professionals working in Basic Health Care Clinics in the 3.1
      Programmatic Area of the City of Rio de Janeiro (Brazil). The article analyzes
      their views on the subject and presents them in light of health-related
      legislation in the Brazilian constitution. It also analyzes the professionals'
      role vis-a-vis users in raising community awareness that health care is one of
      their basic rights. Field data from qualitative social research methodology
      showed a significant heterogeneity in the professionals' conceptions, dividing
      them into two groups: those belonging to teaching institutions and those working
      in institutions providing health care. This analysis shows the strategic role
      that day-to-day relationships between professionals and the community can play in
      the social change process and the establishment of social rights. It also
      discusses the viability of this process in view of the discovery of the
      subjective involvement of the health professionals who promote this process.

PMID- 14676931
TI  - [Attempted control of mucocutaneous leishmaniasis through treatment of diseased
      dogs].
AB  - An attempt was made to control cutaneous leishmaniasis in the municipality of
      Santa Leopoldina, Espirito Santo State, Brazil, by treating infected dogs.
      Another area in the municipality of Afonso Claudio, which is ecologically
      similar, served as the control area, and dogs were left untreated there. In an
      initial survey, 34/141 inhabitants of the first area had positive leishmanin
      tests and 8/26 dogs had cutaneous leishmaniasis, while in the second area 37/127
      individuals had positive leishmanin tests and 7/44 dogs were infected. After
      treatment of the sick dogs in the first area the populations of both areas were
      periodically examined for new infections. More new human infections were observed
      in the control area, but the difference was not statistically significant.

PMID- 14676932
TI  - [The use of risk factor determination for schistosomiasis in endemic areas in
      Brazil].
AB  - This study shows the results of risk factor determination for infection with
      Schistosoma mansoni in endemic areas in Brazil. An association was observed
      between infection with S. mansoni and a number of general conditions: absence of
      drinking water in the home, low individual income, illiteracy, and residence in
      an endemic area for more than five years. In addition to these conditions there
      was also association with a number of habits (risk factors): agricultural and
      domestic activities in open water supplies, swimming, and fishing. Analysis of
      the general conditions that may determine these risk factors indicated that
      provision of drinking water in the home and access to treatment are basic
      measures that could be adopted in many cases in order to prevent or control the
      morbidity of the disease. The efficacy of the use of risk factor determination
      for indication of control measures for this disease is questioned.

PMID- 14676933
TI  - [Relationships between Trypanosoma cruzi transmission cycles in the county of
      Bambui, Minas Gerais, Brazil].
AB  - This study examines recent relationships between domestic and sylvatic
      transmission cycles of T. cruzi in the county of Bambui, MG, Brazil. In the late
      l930s, Panstrongylus megistus was found in 75% of houses. Subsequently, Triatoma
      infestans became the predominant species, found in 20% of urban households and in
      more than 60% of periurban homes. With intense insecticide control campaigns
      between l956 and l969, T. infestans was eradicated from the county, transmission
      of Chagas' disease to man was interrupted, and P. mesgistus appeared in rural
      residences. Samples of T. cruzi isolated by xenodiagnosis and hemoculture from 43
      opossums (Didelphis albiventris) captured in both peridomiciliary and sylvatic
      areas were characterized by isoenzyme analysis and--regardless of isolation
      method--were found to present the Z1 zymodeme profile. Through the "Chagas'
      Disease Epidemiological Surveillance Program", from August l986 to December l988,
      154 specimens of P. megistus were captured by the local population in both
      peridomiciliary and intradomiciliary environments, of which 9.8% were infected
      with T. cruzi. In isoenzyme analyses of l3 T. cruzi strains isolated from these
      triatomines, six were found to be of the Z1 zymodeme (sylvatic transmission
      cycles) and seven were found to be of the Z2 zymodeme (domestic transmission
      cycle). The capture of P. megistus specimens in intradomiciliary environments
      that were naturally infected with parasites of both cycle types indicates an
      overlap of transmission cycles of Chagas' disease in the county of Bambui.
      Further evidence for the interrelationship of the two cycles was provided by the
      isolation of T. cruzi of the Z2 zymodeme from a cat and the participation of the
      dog as a reservoir of Z1 T. cruzi. The presence of P. megistus in the
      peridomiciliary environment represents an important link between the sylvatic and
      intradomestic environments serving as a carrier of Z1 T. cruzi and maintaining
      the transmission cycles of Z2 T. cruzi in the peridomestic and intradomestic
      environments thus providing the potential for a gradual reinfestation of the
      county if the "Epidemiological Surveillance" is interrupted.

PMID- 14676934
TI  - [Health education: a new approach].
AB  - This article describes a series of experiences in the area of Health Education.
      The experiences, carried out with groups of health professionals working in
      institutions, begin with the social relationships in which these professionals
      are involved in their day-to-day work, in contact with other social agents and
      groups. One of the basic assumptions is that social relationships are an
      important aspect of the public health services provided to the population. As a
      result, health workers need specific training in this area to develop and improve
      their professional performance. The experiences show the importance of making
      theoretical and methodological approaches (like Educational Psychodrama and the
      Arvoredo Method) available to these workers. Those who have participated in such
      training programs have considerably improved their professional/social skills.
      One of the basic tenets of these approaches is the constant search for autonomy,
      as an essential element for people to increase awareness of themselves as
      individuals and as citizens, be they health care professionals or users. The
      experiences and methods described in this article may serve as one way of
      reducing the serious gaps in today's public health services.

PMID- 14676935
TI  - [The sanitary question in the modernity-postmodernity debate].
AB  - This work analyzes the sanitary question in the modernity-postmodernity debate.
      Such analyses are performed form a philosophical position that states the crisis
      of Modernity and questions the ideological twist that to itself propitiates
      postmodernity, shutting out questioning views or visions. It propitiates an
      alternative view of politics, thinking of it from the potency plane and giving a
      role to the subject in the decision of producing transformations.

PMID- 14676936
TI  - [Medical anthropology: conceptual and methodological elements for an approach to
      health and disease].
AB  - This paper discusses the relevance, specificity, and potential of the
      anthropological approach to health and illness. Medical anthropology is shown as
      complementary to other approaches that currently deal with public health
      problems. The impact of social and cultural factors on health-related perceptions
      and behaviors is illustrated and commented. A conceptual and methodological
      framework is also proposed to systematize the study of representations and
      practices of communities in the area of public health. The specific contribution
      of the anthropological approach is discussed in terms of the effectiveness of
      public health programs.

PMID- 14676937
TI  - [On the necessary risk of trusting in the future].
AB  - As the result of its centralized, exclusive economic model, Brazil has undergone
      a serious economic, political, and social crisis. The crisis is getting worse
      because the country is simultaneously undergoing extensive demographic,
      epidemiological, and technological changes. There is an urgent need to articulate
      various social groups to challenge and change the ongoing situation. A new
      historical future has to be established so that a different and less unequal
      society can emerge and guarantee better living conditions for coming generations.

PMID- 14676943
TI  - Cardiovascular complications in Type 2 diabetes mellitus depend on the coronary
      angiographic state rather than on the diabetic state.

PMID- 14676944
TI  - Development of autoimmune diabetes in glutamic acid decarboxylase 65 (GAD65)
      knockout NOD mice.
AB  - AIMS/HYPOTHESIS: Type 1 diabetes mellitus, a T-cell-mediated autoimmune disease,
      results from the selective destruction of insulin-producing pancreatic beta
      cells. Autoantibodies against beta-cell components are used clinically as
      sensitive markers of this disease; however, their physiological role has not been
      clear. To investigate the role of glutamic acid decarboxylase 65 (GAD65) in the
      development of the Type 1 diabetes of non-obese diabetic (NOD) mice, we analysed
      and characterised NOD mice with targeted disruption of the GAD65 gene. METHODS:
      GAD65-deficient mice were previously established. After backcrossing the knockout
      mutation onto the NOD genetic background for up to eight generations, female
      littermates of the three resulting genotypes were produced by intercrossing:
      GAD65 +/+ (n=23), GAD65 +/- (n=62), and GAD65 -/- (n=31). RESULTS: The cumulative
      incidence of autoimmune diabetes showed no significant difference among the three
      groups in longitudinal studies using the Kaplan-Meier method. Islet morphology
      showed that the progression of islet infiltration did not differ significantly
      between the three groups. CONCLUSION/INTERPRETATION: The cumulative incidence of
      autoimmune diabetes was not influenced by the GAD65 deficiency. These data
      suggest that GAD65 is not a major regulatory target of beta-cell autoimmunity in
      NOD mice.

PMID- 14676945
TI  - Synergistic action of advanced glycation end products and endogenous nitric oxide
      leads to neuronal apoptosis in vitro: a new insight into selective nitrergic
      neuropathy in diabetes.
AB  - AIMS/HYPOTHESIS: We have previously shown that in diabetes nitrergic neurones
      innervating the urogenital and gastrointestinal organs undergo a selective
      degenerative process. This comprises an initial insulin-reversible decrease in
      neuronal nitric oxide synthase (nNOS) in the axons, followed by apoptosis of the
      nitrergic neurones, a process that is not reversible by insulin. Since apoptosis
      was independent of serum glucose concentrations, and advanced glycation
      endproducts (AGEs) have been implicated in the pathogenesis of diabetic
      complications, we have now measured AGEs in the serum and penis, pyloric
      sphincter and pelvic ganglia of diabetic animals at different times after
      streptozotocin treatment. Furthermore, we have studied their effect in vitro on
      human neuroblastoma (SH-SY5Y) cells in the presence or absence of nNOS
      expression. METHODS: Serum AGEs were measured using fluorometry and ELISA.
      Accumulation of AGEs in the tissues was evaluated with immunohistochemistry. The
      viability, apoptosis and oxidative stress in SH-SY5Y cells were measured upon
      exposure to AGEs or high concentrations of glucose. RESULTS: AGEs increased
      gradually in the serum and tissues of streptozotocin-induced diabetic rats; this
      process was not affected by delayed insulin treatment. In SH-SY5Y cells, AGEs,
      but not high glucose concentrations, increased the reactive oxygen species and
      caspase-3-dependent apoptosis in a synergistic fashion with endogenous nitric
      oxide (NO). Apoptosis was prevented by treatment with a NOS inhibitor, a pan
      caspase inhibitor, a soluble receptor of AGEs or an anti-oxidant, but not an
      inhibitor of soluble guanylate cyclase. CONCLUSIONS/INTERPRETATION: The
      synergistic actions of NO and AGEs account for the irreversible nitrergic
      degeneration in diabetes.

PMID- 14676946
TI  - A genetic linkage map of the Durum x Triticum dicoccoides backcross population
      based on SSRs and AFLP markers, and QTL analysis for milling traits.
AB  - Durum wheat ( Triticum turgidum L. var durum) is mainly produced and consumed in
      the Mediterranean region; it is used to produce several specific end-products;
      such as local pasta, couscous and burghul. To study the genetics of grain-milling
      quality traits, chromosomal locations, and interaction with the environment, a
      genetic linkage map of durum was constructed and the quantitative trait loci QTLs
      for the milling-related traits, test weight (TW) and thousand-kernel weight
      (TKW), were identified. The population constituted 114 recombinant inbred lines
      derived from the cross: Omrabi 5 /Triticum dicoccoides 600545// Omrabi 5. TW and
      TKW were analyzed over 18 environments (sites x years). Single-sequence-repeat
      markers (SSRs), Amplified-fragment-length-polymorphism markers (AFLPs), and seed
      storage proteins (SSPs) showed a high level of polymorphism (>60%). The map was
      constructed with 124 SSRs, 149 AFLPs and 6 SSPs; its length covered 2,288.8 cM
      (8.2 cM/marker). The map showed high synteny with previous wheat maps, and both
      SSRs and AFLPs mapped evenly across the genome, with more markers in the B
      genome. However, some rearrangements were observed. For TW, a high genotypic
      effect was detected and two QTLs with epistasic effect were identified on 7AS and
      6BS, explaining 30% of the total variation. The TKW showed a significant
      transgressive inheritance and five QTLs were identified, explaining 32% of the
      total variation, out of which 25% was of a genetic nature, and showing QTLxE
      interaction. The major TKW-QTLs were around the centromere region of 6B. For both
      traits, Omrabi 5 alleles had a significant positive effect. This population will
      be used to determine other QTLs of interest, as its parents are likely to harbor
      different genes for diseases and drought tolerance.

PMID- 14676948
TI  - An intersubspecific genetic map of Lens.
AB  - A Lens map was developed based on the segregational analysis of five kinds of
      molecular and morphological genetic markers in 113 F(2) plants obtained from a
      single hybrid of Lens culinaris ssp. culinaris x L. c. ssp. orientalis. A total
      of 200 markers were used on the F(2) population, including 71 RAPDs, 39 ISSRs, 83
      AFLPs, two SSRs and five morphological loci. The AFLP technique generated more
      polymorphic markers than any of the others, although AFLP markers also showed the
      highest proportion (29.1%) of distorted segregation. At a LOD score of 3.0, 161
      markers were grouped into ten linkage groups covering 2,172.4 cM, with an average
      distance between markers of 15.87 cM. There were six large groups with 12 or more
      markers each, and four small groups with two or three markers each. Thirty-nine
      markers were unlinked. A tendency for markers to cluster in the central regions
      of large linkage groups was observed. Likewise, clusters of AFLP, ISSR or RAPD
      markers were also observed in some linkage groups, although RAPD markers were
      more evenly spaced along the linkage groups. In addition, two SSR, three RAPD and
      one ISSR markers segregated as codominant. ISSR markers are valuable tools for
      Lens genetic mapping and they have a high potential in the generation of
      saturated Lens maps.

PMID- 14676949
TI  - Genetic diversity of oil palm (Elaeis guineensis Jacq.) germplasm collections
      from Africa: implications for improvement and conservation of genetic resources.
AB  - A total of 723 accessions of oil palm ( Elaeis guineensis Jacq.) from 26
      populations representing ten countries in Africa and one Deli dura family were
      screened for allelic variation at seven enzyme loci from six enzyme systems using
      starch gel electrophoresis. On average, 54.5% of the loci were polymorphic (0.99
      criterion). The average and effective number of alleles per locus was 1.80 and
      1.35, respectively. Mean expected heterozygosity was 0.184, with values ranging
      from 0.109 (population 8, Senegal) to 0.261 (population 29, Cameroon). The
      genetic differentiation among populations was high (F(ST)=0.301), indicating high
      genetic divergence. The calculation of F(ST) by geographic zones revealed that
      the high F(ST) was largely due to F(ST) among populations in West Africa,
      suggesting diversifying selection in this region. The mean genetic distance
      across populations was 0.113. The lowest genetic distance (D) was observed
      between population 5 from Tanzania and population 7 from the Democratic Republic
      of the Congo (0.000) and the highest was found between population 4 from
      Madagascar and population 13 from Sierra Leone (0.568). The total gene flow
      across oil palm populations was low, with an Nm of 0.576, enhancing genetic
      structuring, as evident from the high F(ST) values. UPGMA cluster analysis
      revealed three main clusters; the western outlying populations from Senegal and
      Sierra Leone were in one cluster but separated into two distinct sub-clusters;
      the eastern outlying populations from Madagascar were in one cluster; the
      populations from Angola, Cameroon, The Democratic Republic of the Congo, Ghana,
      Tanzania, Nigeria and Guinea were in one cluster. The Deli dura family seems to
      be closely related to population 6 from Guinea. Oil palm populations with high
      genetic diversity-i.e. all of the populations from Nigeria, Cameroon and Sierra
      Leone, population 6 of Guinea, population 1 of Madagascar and population 2 of
      Senegal should be used in improvement programmes, whereas for conservation
      purposes, oil palm populations with high allelic diversity (A(e)), which include
      populations 22 and 29 from Cameroon, populations 39 and 45 from Nigeria,
      population 6 from Guinea, populations 5 and 13 from Sierra Leone and population 1
      from Madagascar should be selected for capturing as much genetic variation as
      possible.

PMID- 14676950
TI  - Fundamentals and systematics of the non-statistical distributions of isotopes in
      natural compounds.
AB  - The intermolecular and intramolecular non-statistical distribution of the
      isotopes of the bio-elements in natural compounds must obviously be controlled by
      logical principles. However, a critical review of the available isotope patterns
      of natural compounds indicates that a previously discussed general thermodynamic
      order and its mechanistic foundation cannot satisfactorily explain all
      experimental data. In the present contribution it is shown that a partial
      thermodynamic order can eventually be attained for defined positions and
      compounds under steady-state conditions of metabolism. However, as biological
      systems are generally open and irreversible, many other in vivo isotope
      discriminations are dominated by kinetic isotope effects, even in context with
      reversible reactions. On the other hand, kinetic isotope effects can only become
      effective in vivo in combination with metabolic branching and the implied isotope
      shifts of the products are balanced by their relative yields. In vivo, the
      influences of thermodynamic and kinetic isotope effects are modulated by
      interferences of the actual metabolic conditions, such as the nature and kind of
      precursors, alternative metabolic pathways, metabolite pools and fluxes, and by
      reaction mechanisms. This is demonstrated by giving examples for the isotopes of
      hydrogen, carbon, nitrogen, oxygen and sulfur, while simultaneously the
      particularities of the individual elements are elaborated. The resulting general
      theory of the origin of non-statistical isotope distributions in biological
      systems permits the interpretation and prediction of isotope patterns and
      provides the scientific basis for the elucidation of biosyntheses and origin
      assignments of natural compounds.

PMID- 14676951
TI  - Mating success and fidelity to territories in a fallow deer lek: a female removal
      experiment.
AB  - A lek is a clump of male territories that females visit only for mating; it is
      quite a rare mating system among mammals. As we wanted to investigate the role of
      past male mating success on their fidelity to lek territories, we displaced
      fallow deer females by a lek (Lek A), i.e. we removed the resources for rutting
      males. They moved to a new area followed by some of the territorial males
      ('mobile' males) where they established a new lek (Lek B). Other males
      ('faithful' males) stayed on Lek A. The former had lower mating success and
      dominance ranking in the early, undisturbed part of the rut. After disturbance,
      the MS of faithful males was much reduced, while that of mobile males was higher
      on Lek B than it had been on Lek A. We then disturbed Lek B. Females returned to
      Lek A, and the mating success of faithful males reverted to its original level.
      Past mating success was the main factor predicting whether a male was faithful or
      mobile. We illustrated for the first time the importance of past experience in
      promoting lek fidelity; this experiment gives an insight into the mechanisms
      leading to the traditional use of leks.

PMID- 14676952
TI  - The infrabuccal pellet piles of fungus-growing ants.
AB  - Fungus-growing ants (Attini) live in an obligate mutualism with the fungi they
      cultivate for food. Because of the obligate nature of this relationship, the
      success of the ants is directly dependent on their ability to grow healthy fungus
      gardens. Attine ants have evolved complex disease management strategies to reduce
      their garden's exposure to potential parasitic microbes, to prevent the
      establishment of infection in their gardens, and to remove infected garden
      sections. The infrabuccal pocket, a filtering device located in the oral cavity
      of all ants, is an integral part of the mechanisms that leaf-cutter ants use to
      prevent the invasion and spread of general microbial parasites and the specific
      fungal-garden parasite Escovopsis. Fungus-growing ants carefully groom their
      garden, collecting general debris and pathogenic spores of Escovopsis in their
      infrabuccal pocket, the contents of which are later expelled in dump chambers
      inside the nest or externally. In this study we examined how a phylogenetically
      diverse collection of attine ants treat their infrabuccal pellets. Unlike leaf
      cutters that deposit their infrabuccal pellets directly in refuse piles, ants of
      the more basal attine lineages stack their infrabuccal pellets in piles located
      close to their gardens, and a separate caste of workers is devoted to the
      construction, management, and eventual disposal of these piles.

PMID- 14676953
TI  - The dinosaurian origin of feathers: perspectives from dolphin (Cetacea) collagen
      fibers.
AB  - The early origin of birds is a hotly disputed debate and may be broadly framed as
      a conflict between paleontologists and ornithologists. The paleontological
      emphasis has shifted from Archaeopteryx and its origins to recent finds of
      Cretaceous birds and "feathered" dinosaurs from China. The identification of
      alleged feathers has, however, relied principally on the visual image. Some
      workers have interpreted these integumentary structures as collagen fibers. To
      test the latter hypothesis, using light microscopy, collagen from the hypodermis
      (blubber) and subdermal connective tissue sheath was examined from a dolphin that
      had been buried for a year as part of an experiment. Within the blubber, toward
      the central thicker parts of the material, the collagen fibers had compacted and
      the three-dimensional latticework of normal blubber had more or less collapsed.
      Chromatographic analysis of the blubber revealed pronounced oxidation of the
      unsaturated lipids, probably accounting for the collapse of the latticework.
      Fibers normally bound together in bundles became separated into individual fibers
      or smaller bundles by degradation of the glue-like substance binding them
      together. These degraded collagen fibers show, in many instances, feather-like
      patterns, strikingly reminiscent of many of those identified as either
      "protofeathers" or "modern" feathers in dromaeosaurid dinosaurs. The findings
      throw serious doubt on the virtually complete reliance on visual image by
      supporters of the feathered dinosaur thesis and emphasize the need for more
      rigorous methods of identification using modern feathers as a frame of reference.
      Since collagen is the main fiber type found in most supporting tissues, the
      results have wide implications regarding the degradation and fossilization of
      vertebrate integument, such as that of the ichthyosaurs, dinosaurs and birds.

PMID- 14676954
TI  - Gnamptogenys hartmani Wheeler (Ponerinae: Ectatommini): an agro-predator of
      Trachymyrmex and Sericomyrmex fungus-growing ants.
AB  - The fungus gardens of fungus-growing ants are a potentially valuable resource for
      exploitation by natural enemies, but few of these antagonistic interactions have
      been studied. Here we describe key aspects of the behavioral ecology of
      Gnamptogenys hartmani (Ponerinae: Ectatommini), a specialized "agro-predator" of
      Trachymyrmex and Sericomyrmex fungus-growing ants in Panama. Raiding columns of
      G. hartmani attack and usurp nests with remarkably little effort: a few intruding
      workers are sufficient to cause panic among the attine ants and make them abscond
      from the nest. Both G. hartmani larvae and adults consume the fungus and the host
      brood, after which the colony migrates to a new fungus-growing ant nest
      discovered by scouting workers. The morphology of the G. hartmani larval
      mouthparts is similar to that of Gnamptogenys species with a non-fungal diet.
      However, we suggest that the presence of long spinules on the larval mandibles in
      the genus Gnamptogenys, comparable to those found in attine larvae, may have pre
      adapted G. hartmani to fungus eating. G. hartmani workers do not actively
      maintain or modify fungus gardens, which makes them less efficient exploiters
      than Megalomyrmex, the only other agro-predatory ant species known so far.

PMID- 14676955
TI  - Closely associated theropod trackways from the Jurassic of Zimbabwe.
AB  - Eighty-eight tracks of large theropod dinosaurs were found in the mid-Jurassic of
      Zimbabwe. Among the tracks, at least five adjacent trackways are recorded. The
      adjacent tracks were probably made by animals traveling as a group, given that
      they are in relatively close succession; that there are three overlapping tracks
      (among just 23) suggesting reasonably close associations of the animals; that all
      the tracks are apparently of the same ichnotaxon; that the preservational types
      of the tracks are similar; and that the tracks are all of animals traveling in
      one general direction closely associated in time (there are no returning tracks
      of the same animals or of those of other species; presence of such tracks would
      be highly probable if the tracks were made over a period of time of even several
      hours). Nearby, recently discovered giant sauropod tracks, the first in sub
      Saharan Africa, indicate a realistic potential of predator/prey interactions
      between the two groups of dinosaurs.

PMID- 14676956
TI  - The reproductive choices of eavesdropping female black-capped chickadees, Poecile
      atricapillus.
AB  - In animals where males engage in signalling interactions, females might evaluate
      male-male contests to inform their reproductive choices. We used interactive
      playback to engage territorial male black-capped chickadees (Poecile
      atricapillus) of known dominance status in countersinging contests with an
      aggressive or submissive opponent. Previous analysis of these data showed that
      high-ranking males who received aggressive playback were more likely to be
      cuckolded. Here we describe the particular reproductive decisions of females
      whose partners received aggressive versus submissive playback. The proportion of
      extra-pair young per brood was higher for females paired to high-ranking males
      that received aggressive playback compared to submissive playback, and similar to
      levels in broods of females paired to low-ranking males. We found no strong
      predictors of whether high-ranking subjects lost paternity following aggressive
      playback. Females usually preferred extra-pair sires with high dominance status.
      When females had extra-pair fertilizations with low-ranking males, females chose
      males who had received submissive playback. We conclude that females mated to
      aggressive-playback, high-ranking males pursued mixed mating strategies similar
      to those of females mated to low-ranking males. Our results support the idea that
      male performance in song contests may influence multiple aspects of female
      reproductive choices.

PMID- 14676958
TI  - Congenital cystic eye.
AB  - BACKGROUND: Congenital cystic eye is a rare ocular and orbital malformation
      describing an intraorbital cavity lined by neuroglial tissue. Clinical and
      histopathologic findings of a 3-year-old boy with a congenital cystic eye are
      presented. METHODS: A 4-year-old otherwise healthy boy with anophthalmia of the
      right eye was referred because of progressive volume enlargement of his
      congenital cystic lesion of the right orbit. Imaging techniques revealed a
      hyperintense cystic tumor with calcifications of the wall. There was no evidence
      of a globe, no communication to the intracranial space and a normal bony orbit.
      The mass was excised and a 20-mm silicone orbital implant inserted. RESULTS:
      Microscopic examination of the cyst revealed irregularly shaped layers of
      fibrovascular tissue lined by neuroglial tissue with calcified bodies and
      positive immunohistochemical staining for glial fibrillary acid protein (GFAP),
      neuron-specific enolase (NSE) and neurofilament protein (NF). No structures like
      cornea, lens, retinal pigmented epithelium or rosettes were identified.
      CONCLUSIONS: Congenital cystic eye is a primary developmental abnormality of the
      globe caused by an invaginational arrest of the primary optic vesicle between the
      2-mm and 7-mm stages of fetal development. The luminal neuroglial tissue contains
      dystrophic calcified bodies and degenerated primitive nerve fibers. The
      enlargement of the cyst may be due to fluid produced by glial tissue. The
      differential diagnoses for cystic anomalies without epithelial lining include
      microphthalmia with cyst, microphthalmia with cystic teratoma, ectopic brain
      tissue and meningoencephalocele.

PMID- 14676960
TI  - Retinal complications of intravitreal injections of triamcinolone acetonide.

PMID- 14676959
TI  - Iodide protection from UVB irradiation-induced degradation of hyaluronate and
      against UVB-damage of human conjunctival fibroblasts.
AB  - BACKGROUND: To determine whether iodide protects from UVB irradiation-induced
      destruction of hyaluronate and against UVB injury of cultured human conjunctival
      fibroblasts. METHODS: Hyaluronate and primary cultured human conjunctival
      fibroblasts were incubated with various concentrations of iodide and then exposed
      to UV light irradiation of 312 nm. Hyaluronate destruction was determined by
      viscosity measurements. Cell viability was assessed with MTT assay. RESULTS:
      Iodide protects hyaluronate from UVB light-induced degradation of this
      macromolecule in a concentration-dependent manner. Incubation of human
      conjunctival fibroblasts with iodide inhibited cells from damage by UVB light.
      CONCLUSION: Iodide protects hyaluronate, a component of tear fluid and tissues of
      the anterior part of the eye, against UVB light-induced degradation. Also, injury
      of human conjunctival cells can be prevented by incubation with iodide before UVB
      irradiation. The mechanism of protection is likely to include an antioxidative
      reaction. To support the natural defence mechanisms of the eyes, the
      administration of an antioxidant such as iodide to artificial tears, for example,
      may help to prevent the damage of the eye provoked by oxidative stress.

PMID- 14676961
TI  - Modelling of carcinogenesis and low-dose hypersensitivity: an application to lung
      cancer incidence among atomic bomb survivors.
AB  - Lung cancer incidence among the atomic bomb survivors from Hiroshima and Nagasaki
      was analysed with the two-step clonal expansion (TSCE) model of carcinogenesis.
      For the baseline incidence, a new set of model parameters is introduced, which
      can be determined with a higher precision than the parameter sets previously
      used. The effect of temporal changes in the smoking behaviour on the lung cancer
      incidence is modelled by allowing initiation, inactivation and division rates of
      intermediate cells to depend on the year of birth. The TSCE model is further
      developed by implementing low-dose hypersensitivity in the survival of lung
      epithelial cells. According to the model fit to the data, the acute gamma
      exposure of the atomic bomb survivors does not only result in the conventional
      initiating effect, but also in a promoting effect for lung cancer. Compared to
      the model in which radiation acts merely on initiation, the new model is in
      better agreement with the age-at-exposure dependence in the data, and it does not
      predict an unexpected increase of the excess relative risk (ERR) at 40 years
      after exposure. According to the new model, the ERR at low doses increases non
      linearly with dose, especially during the first 10 years after exposure to older
      persons.

PMID- 14676962
TI  - Soil-to-grain transfer of fallout 137Cs for 28 winter wheat cultivars as observed
      in field experiments.
AB  - In order to find wheat cultivars with a minimum soil-to-grain transfer of fallout
      (137)Cs, 28 winter wheat cultivars were investigated at 3 different sites with
      different soil types in Bavaria, Germany. Each cultivar was grown on an area of
      10 m(2) and harvested in August 1999. The soil-to-grain concentration ratios
      (C(r)) of (137)Cs varied by a factor of up to 3 from cultivar to cultivar at a
      given site and from site-to-site for a given cultivar. The mean C(r) values at
      the three sites, 4.2 x 10(-4), 4.9 x 10(-4) and 7.5 x 10(-4), differed
      significantly. The fact that no cultivar showed similar C(r) values at the three
      sites indicates a strong influence of the soil on C(r). The cultivars Flair,
      Kornett and Previa showed a minor uptake of (137)Cs compared with the mean of all
      cultivars at each site. Unlike (137)Cs, the (40)K concentrations in the wheat
      grains varied only within a small range (122-190 Bq kg(-1)) at each site, which
      is due to the potassium regulation by the plants. For both radionuclides, the
      differences between the root uptake characteristics of the cultivars may not only
      be explained by an inter-cultivar variability due to genetic differences between
      the cultivars, but also by an intra-cultivar variability due to different soil
      conditions.

PMID- 14676963
TI  - Emergency peripartum hysterectomy in Northern Jordan: indications and obstetric
      outcome (an 8-year review).
AB  - OBJECTIVE: To review cases of emergency peripartum hysterectomy regarding their
      incidence, risk factors, indications and complications and their results were
      carefully analysed. MATERIALS AND METHODS: A retrospective study of cases of
      emergency peripartum hysterectomy which were performed in the period between
      February 1994 and February 2002 at the Princess Badeea Teaching Hospital in
      Northern Jordan. Demographic and clinical data were extracted and closely
      interpreted RESULTS: In the study period there were a 70,252 deliveries and 61
      cases of emergency peripartum hysterectomies. The overall incidence was 0.87
      peripartum hysterectomies per 1,000 deliveries. There were 50 cases (82%)
      delivered by caesarean section and 11 cases (18%) were delivered vaginally.
      Caesarean hysterectomy was performed in 50 cases and postpartum hysterectomy was
      performed in 11 cases. Total hysterectomy was performed in 39 cases (64%) and
      subtotal hysterectomy was performed in 22 cases (36%). The main indications for
      hysterectomy were morbidly adherent placenta (47.5%), ruptured uterus (27.9%) and
      uncontrollable haemorrhage from uterine atony (21.3%). There were two maternal
      deaths and 7 cases of stillbirths and 4 cases of early neonatal deaths.
      CONCLUSION: Peripartum hysterectomy is a dramatic with high risk but a life
      saving operation. It is usually associated with significant maternal and fetal
      morbidity and mortality. Obstetricians should identify patients at risk and
      anticipate the procedure and complications, as early intervention and proper
      management facilitate optimal outcome.

PMID- 14676964
TI  - Infected endometrioma in pregnancy masquerading as acute appendicitis.
AB  - BACKGROUND: A pregnancy complicated by ovarian endometrioma is rare. Other
      complications of ovarian endometrioma in pregnancy, i.e., rupture and infection
      are also rare. CASE: A 35-year-old woman, gravida 2, para 0-0-1-0, at 35 weeks'
      pregnancy, came to the hospital with a right abdominal pain. She also had a
      history of diarrhea. She had history of infertility and preexisting right
      endometrioma. The investigations revealed leukocytosis with neutrophils
      predominant. The preoperative diagnosis was acute appendicitis. Infected right
      ovarian endometrioma was demonstrated during exploratory laparotomy, opened and
      drainage of the right endometrioma and appendectomy were performed. The final
      diagnosis was infected ovarian endometrioma in pregnancy, later confirmed by a
      pathological report. CONCLUSION: Although complication of ovarian endometrioma
      such as infected endometrioma during pregnancy is rare, it should be included in
      the differential diagnosis of pelvic pain during pregnancy, especially in the
      patient who has history of ovarian endometrioma.

PMID- 14676965
TI  - New concepts in the treatment of ankle joint fractures. The IP-XS (XSL) and IP
      XXS (XXSL) nail in the treatment of ankle joint fractures.
AB  - INTRODUCTION: The most important factor in the treatment of ankle joint fractures
      is stable anatomical reconstruction of the syndesmosis and joint surface. In the
      course of this, attention must be paid to soft-tissue damage with the risk of
      deep infections. Early functional therapy and exercise tolerance must be called
      for. The choice of surgical access route, in particular in the case of critical
      arterial circulation, and the possible irritation of the soft tissue by the
      osteosynthesis material prompted us to seek alternative osteosynthesis
      techniques. MATERIAL AND METHODS: Following a preclinical study and very good
      initial results with the XS nail in the treatment of patella and olecranon
      fractures, this was now also used for ankle joint fractures at the medial
      malleolus and lateral malleolus. In the period from 5/2000 to 1/2002, 194 ankle
      joint fractures were treated using the XS nail. These were predominantly Weber B,
      C and bimalleolar fractures. In the case of ankle joint fractures, osteosynthesis
      was carried out following precise open fracture repositioning. In the case of
      isolated fibula fractures, early loading was allowed within 1 week; in the case
      of bimalleolar fractures, there was immediate partial loading with 20 kg for 4
      weeks, after which they were subjected to full loading. Where there was an
      additional Volkmann fracture, we allowed only immediate partial loading with 10
      kg for 6 weeks. All 194 patients were observed prospectively, and 162 (83.5%)
      could be followed up after 15 months. The results were classified according to
      the scale described by Olerud. RESULTS: It has been possible to follow up 162
      patients, with an average age of 49.7 years. There were 62 (38.3%) Weber B and 45
      (27.8%) Weber C fractures. In 55 (34.0%) cases, bimalleolar fractures were
      present. According to the Olerud score, 95 (58.6%) of the patients had an
      excellent outcome, 54 (33.3%) a good one, 9 (5.5%) a fair one and 4 (2.5%) an
      unsatisfactory outcome. In 3 cases a threaded wire dislocation occurred, without
      complications. Two mesh graft transplants were necessary; otherwise, there were
      no soft-tissue problems requiring review. One pseudarthrosis was seen.
      CONCLUSION: The XS nail which is introduced here fulfils the requirements made of
      an implant as regards maximum protection of soft tissue, secure fracture fixation
      and early exercise tolerance, including ankle fractures. No implant dislocation,
      no deep infection and no re-osteosynthesis were observed. Its advantages over
      conventional techniques lie precisely in the treatment of complex fractures and
      for patients with poor bone, vascular and soft-tissue situations.

PMID- 14676966
TI  - L-glucose absorption in house sparrows (Passer domesticus) is nonmediated.
AB  - We previously demonstrated in intact house sparrows substantial absorption in
      vivo of L-glucose, the stereoisomer of D-glucose that is assumed not to interact
      with the intestine's D-glucose transporter. Results of some studies challenge
      this assumption for other species. Therefore, we tested it in vitro and in vivo,
      based on the principle that if absorption of a compound (L-glucose) is mediated,
      then absorption of its tracer will be competitively inhibited by high
      concentrations of either the compound itself or other compounds (e.g., D-glucose)
      whose absorption is mediated by the same mechanism. An alternative hypothesis
      that L-glucose absorption is primarily paracellular predicts that its absorption
      in vivo will be increased (not decreased) in the presence of D-glucose, because
      the permeability of this pathway is supposedly enhanced when Na(+)-coupled
      glucose absorption occurs. First, using intact tissue in vitro, we found that
      uptake of tracer-radiolabeled L-glucose was not significantly inhibited by high
      concentrations (100 mM) of either L-glucose or 3-O-methyl-D-glucose, a non
      metabolizable but actively transported D-glucose analogue. Second, using intact
      house sparrows, we found that fractional absorption of the L-glucose tracer was
      significantly increased, not reduced, when gavaged along with 200 mM 3-O-methyl-D
      glucose. This result was confirmed in another experiment where L-glucose
      fractional absorption was significantly higher in the presence vs. absence of
      food in the gut. The greater absorption was apparently not due simply to longer
      retention time of digesta, because no significant difference was found among
      retention times. Our results are consistent with the idea that L-glucose is
      absorbed in a non-mediated fashion, largely via the paracellular pathway in vivo.

PMID- 14676967
TI  - Structure-Activity Studies of Brassinosteroids and the Search for Novel Analogues
      and Mimetics with Improved Bioactivity.
AB  - A number of novel brassinosteroid analogues were synthesized and subjected to the
      rice leaf lamina inclination bioassay. Modified B-ring analogues included lactam,
      thiolactone, cyclic ether, ketone, hydroxyl, and exocyclic methylene derivatives
      of brassinolide. Those derivatives containing polar functional groups retained
      considerable bioactivity, whereas the exocyclic methylene compounds were devoid
      of activity. Analogues containing normal alkyl and cycloalkyl substituents at C
      24 (in place of the isopropyl group of brassinolide) showed an inverse
      relationship between activity and chain length or ring size, respectively. The
      corresponding cyclopropyl and cyclobutyl derivatives were significantly more
      active than brassinolide and appear to be the most potent brassinosteroids
      reported to date. When synergized with the auxin indole-3-acetic acid (IAA),
      their bioactivity can be further enhanced by 1-2 orders of magnitude. The
      cyclopropyl derivative, when coapplied with the auxin naphthaleneacetic acid,
      gave a significant increase in yield of wheat in a field trial. Certain 25- and
      26-hydroxy derivatives are known metabolites of brassinosteroids. All of the C-25
      stereoisomers of 25-hydroxy, 26-hydroxy, and 25,26-dihydroxy derivatives of
      brassinolide were prepared and shown to be much less active than brassinolide.
      This indicates that they are likely metabolic deactivation products of the parent
      phytohormone. A series of methyl ethers of brassinolide was synthesized to block
      deactivation by glucosylation of the free hydroxyl groups. The most significant
      finding was that the compound where three of the four hydroxyl groups (at C-3, C
      22, and C-23) had been converted to methyl ethers retained substantial
      bioactivity. This type of modification could, in theory, allow brassinolide or 24
      epibrassinolide to resist deactivation and thus offer greater persistence in
      field applications. A series of nonsteroidal mimetics of brassinolide was
      designed and synthesized. Two of the mimetics showed significant bioactivity and
      one had bioactivity comparable to brassinolide, but only when formulated and
      coapplied with IAA. They thus represent the first nonsteroidal analogues
      possessing brassinosteroid activity.

PMID- 14676968
TI  - Brassinosteroid-Mediated Stress Responses.
AB  - Brassinosteroids (BRs) are a group of naturally occurring plant steroidal
      compounds with wide-ranging biological activity that offer the unique possibility
      of increasing crop yields through both changing plant metabolism and protecting
      plants from environmental stresses. In recent years, genetic and biochemical
      studies have established an essential role for BRs in plant development, and on
      this basis BRs have been given the stature of a phytohormone. A remarkable
      feature of BRs is their potential to increase resistance in plants to a wide
      spectrum of stresses, such as low and high temperatures, drought, high salt, and
      pathogen attack. Despite this, only a few studies aimed at understanding the
      mechanism by which BRs promote stress resistance have been undertaken. Studies of
      the BR signaling pathway and BR gene-regulating properties indicate that there is
      cross-talk between BRs and other hormones, including those with established roles
      in plant defense responses such as abscisic acid, jasmonic acid, and ethylene.
      Recent studies aimed at understanding how BRs modulate stress responses suggest
      that complex molecular changes underlie BR-induced stress tolerance in plants.
      Analyses of these changes should generate exciting results in the future and
      clarify whether the ability of BRs to increase plant resistance to a range of
      stresses lies in the complex interactions of BRs with other hormones. Future
      studies should also elucidate if BRI1, an essential component of the BR receptor,
      directly participates in stress response signaling through interactions with
      ligands and proteins involved in plant defense responses.

PMID- 14676969
TI  - Brassinosteroid Signal Transduction: A Mix of Conservation and Novelty.
AB  - Brassinosteroids (BRs) are a unique class of plant steroids that are structurally
      similar to animal steroid hormones and play important roles in plant growth and
      development. Unlike the animal steroids, which bind to classical intracellular
      steroid receptors that directly modulate gene activities after translocation into
      the nucleus, the plant steroids rely on transmembrane receptor kinases to
      activate a phosphorylation cascade to regulate gene expression. Recent genetic
      and biochemical studies have identified several critical BR signaling components
      and revealed a striking mechanistic similarity between the plant steroid
      signaling pathway and several well-studied animal signaling cascades involving a
      receptor kinase and glycogen synthase kinase 3 (GSK3). A working model for BR
      signal transduction proposes that BR initiates its signaling pathway by promoting
      heterodimerization of two transmembrane receptor-like kinases at the cell
      surface, leading to inhibition of a GSK3 kinase and subsequent stabilization and
      nuclear accumulation of two GSK3 substrates that regulate BR-responsive genes.
      Such a simple model provides a framework for continued investigation of molecular
      mechanism(s) of plant steroid signaling.

PMID- 14676970
TI  - Genomic Brassinosteroid Effects.
AB  - Detailed analysis of brassinosteroid (BR)-regulated genes can provide evidence of
      the molecular basis of BR effects. Classical techniques (such as subtractive cDNA
      cloning) as well as cDNA and oligonucleotide microarrays have been applied to
      identify genes which are upregulated or downregulated after BR treatment or are
      differently expressed in BR-deficient or -insensitive mutants compared with wild
      type plants. Genes encoding cell-wall-modifying enzymes, enzymes of the BR
      biosynthetic pathway, auxin response factors, and transcription factors are
      subject to BR regulation. Effects on several other metabolic pathways and
      interactions with other phytohormones have been reported as well, although some
      of these effects may depend on certain environmental conditions (for example,
      light/dark or stress), the developmental stage of the plants, and tissue types.
      The identification of components of the BR signal transduction pathway revealed
      different modes of transcriptional control in animals and plants. Steroid
      signaling in plants comprises the plasma membrane receptor kinases BRI1 and BAK1
      and intracellular protein phosphorylations. Thus, BR signaling in plants is
      reminiscent of growth factor and TGF-beta signal transduction in animals. The
      phosphorylation cascade could be a basis of extensive signaling cross-talk and
      thereby explain the complexity of BR responses.

PMID- 14676971
TI  - Physiological Actions of Brassinosteroids: An Update.
AB  - In general, this overview covers literature from 1999 until early 2003. Topics
      covered include aspects of the biosynthesis and transport of brassinosteroids,
      their effects on cell division, expansion, and differentiation, and their effects
      on whole plants, including source-sink relations and other endogenous
      interactions. Some interactions with environmental signals are discussed, as well
      as results that may promise applications in future. Topics that warrant further
      investigation of the roles of BRs include phenotypic variability, reproductive
      physiology, senescence, branching, and apical dominance, whereas topics in which
      possible roles for BRs are relatively unexplored include lignification,
      phototropism, photoperiodism, and endogenous rhythms.

PMID- 14676972
TI  - Brassinosteroid Mutants of Crops.
AB  - Plant steroid hormones, brassinosteroids (BRs), were originally isolated from
      extracts of pollen because of their growth-promoting properties and their
      potential use for enhancing crop production. Mutants in the biosynthesis,
      metabolism, and signaling of brassinolide (BL), the most bioactive BR, are
      important resources in helping to establish BRs' essential role in plant growth
      and development. The dark green and distinctive dwarf phenotype of BR-related
      mutants identified in pea, tomato, and rice highlights the importance of BRs in
      crops. These mutants are helping to elucidate both the conserved and the unique
      features of BR biosynthesis and signaling. Such insights are providing the key
      knowledge and understanding that will enable the development of strategies
      towards the production of crops with enhanced qualities.

PMID- 14676973
TI  - The Influence of Chemical Genetics on Plant Science: Shedding Light on Functions
      and Mechanism of Action of Brassinosteroids Using Biosynthesis Inhibitors.
AB  - When exogenous chemicals allow rapid, conditional, reversible, selective, and
      dose-dependent control of biological functions, they act like conditional
      mutations, either inducing or suppressing the formation of a specific phenotype
      of interest. Exploration of the small molecules that induce the brassinosteroid
      (BR) deficient-like phenotype in Arabidopsis led us to identify brassinazole as
      the first candidate for a BR biosynthesis inhibitor. Brassinazole treatment
      reduced BR content in plant cells. Investigation of target site(s) of
      brassinazole revealed that the compound directly binds to the DWF4 protein, a
      cytochrome P450 monooxygenase that catalyzes 22-hydroxylation of the side chain
      of BRs. These results suggest that brassinazole is a BR biosynthesis inhibitor.
      There are currently at least two BR biosynthesis inhibitors that act like
      conditional mutations in BR biosynthesis. They allow the investigation of the
      functions of BRs in a variety of plant species. Application of BR biosynthesis
      inhibitors to a standard genetic screen to identify mutants that confer
      resistance to these inhibitors allowed the identification of new components
      working in BR signal transduction. This method has advantages over mutant screens
      using BR-deficient mutants as a background. Development of chemicals that induce
      phenotypes of interest is now emerging as a useful way to study biological
      systems in plants and this would be a complement to classical biochemical and
      genetic methods.

PMID- 14676974
TI  - Recent Advances in Brassinosteroid Research: From Molecular Mechanisms to
      Practical Applications.

PMID- 14676975
TI  - Qualitative assessment of tumor vascularity in hepatocellular carcinoma by
      contrast-enhanced coded ultrasound: comparison with arterial phase of dynamic CT
      and conventional color/power Doppler ultrasound.
AB  - The purpose of this study was to evaluate the detection rate of tumor vessels and
      vascularity in hepatocellular carcinoma (HCC) by contrast-enhanced coded US using
      Levovist, and to compare with conventional color/power Doppler US (CDUS) and
      dynamic CT. Ninety nodules (72 hypo/isoechoic nodules, 18 hyperechoic nodules) in
      61 patients were studied. We observed tumor vessels by continuous transmission at
      the early vascular phase (40 s following administration of Levovist) and
      vascularity by intermittent transmission (intervals of 2-3 s) at the late
      vascular phase (40 to approximately 120 s). The detection rate of tumor vessels
      at the early vascular phase was 97% in hypo/isoechoic nodules and 70% in
      hyperechoic nodules with high density in dynamic CT being higher than that by
      CDUS. Tumor vascularity at the late vascular phase in hypo/isoechoic and
      hyperechoic nodules was hyper-enhancement in 78 and 40%, iso-enhancement in 19
      and 40%, and hypo-enhancement in 3 and 0%, respectively. The detection rates of
      tumor vessels and vascularity in hyperechoic nodules were similar to those by
      CDUS. The detection rates of tumor vessels and vascularity were not affected by
      the tumor size in HCC tumors with high density in dynamic CT. Contrast-enhanced
      US with Levovist was superior to CDUS and equal to dynamic CT to assess tumor
      vessels in hypo/isoechoic nodules. Although it was equal to CDUS for hyperechoic
      nodules, this modality is useful in evaluating tumor hemodynamics.

PMID- 14676976
TI  - Clinical evaluation of a breathing protocol for PET/CT.
AB  - The aim of this study was to assess the frequency and severity of respiration
      induced curvilinear respiration artifacts (RICA) on co-registered positron
      emission tomography/computed tomography (PET/CT) images acquired on a combined
      PET/CT scanner before and after modifying the respiration protocol for CT
      scanning, with retrospective analysis of two groups of 100 patients each, before
      and after implementing a respiration protocol with breath-hold (BH) in the normal
      expiration position for the acquisition of the CT images. The CT data were used
      as attenuation map and for image co-registration. A ranking of co-registered
      PET/CT and PET images (including maximum intensity projection) was done by two
      observers in consensus using a scale from 0 to 3. Zero indicated that no RICA was
      visible and 1, 2, and 3 described artifact with increasing severity. A
      significant difference in RICA occurrence was found between the two groups (
      p<0.0001). There was a 45% decrease of artifact frequency when using the normal
      expiration protocol and a 68% decrease of grade-2 and grade-3 artifacts (
      p=0.004). The results of this study suggest that BH during the normal expiration
      position for CT scanning can be recommended to reduce the occurrence and the
      severity of RICA on PET/CT.

PMID- 14676977
TI  - Two potential mechanisms of oxaliplatin-induced haemolytic anaemia in a single
      patient.
AB  - Only two patients with adequately documented oxaliplatin-induced autoimmune
      haemolytic anaemia have previously been reported. We report here a third patient
      with an immune-haematological finding favouring a bispecific mechanism (immune
      complex and penicillin type) of oxaliplatin-induced haemolysis.

PMID- 14676980
TI  - A discussion of the article, "Unexpected bleeding caused by arterial variation
      inferolateral to levator Palpebrae," by B.G. Kim, M.D., D.Y. Youn, M.D., E.S.
      Yoon, M.D., Y.G. Lee, M.D., H. Jin, M.D., J.W. Hahm, M.D., and J.D. Seo, M.D.

PMID- 14676982
TI  - Peter Ell: portrait of an editor.

PMID- 14676983
TI  - Effects of CO2 on the formation of flavour volatiles during fermentation with
      immobilised brewer's yeast.
AB  - Immobilised-cell fermentors offer great benefits compared to traditional free
      cell systems. However, a major problem is unbalanced flavour production when
      these fermentors are used for the production of alcoholic beverages. One of the
      keys to obtaining better control over flavour formation may be the concentration
      of dissolved CO2, which has inhibitory effects on yeast growth and metabolism.
      This article demonstrates that the presence of immobilisation matrices
      facilitates the removal of CO2 from the liquid medium, which results in a low
      level of dissolved CO2 during fermentation. Moreover, the formation of volatile
      higher alcohols and esters was greatly enhanced in the immobilised-cell system
      when compared to the free cell system. By sparging a CO2 flow (45 ml/min) into
      the immobilised-cell system, cell growth was reduced by 10-30% during the active
      fermentation stage, while the fermentation rate was unaffected. The uptake of
      branched-chain amino acids was reduced by 8-22%, and the formation of higher
      alcohols and esters was reduced on average by 15% and 18%, respectively. The
      results of this study suggest that mismatched flavour profiles with immobilised
      cell systems can be adjusted by controlling the level of dissolved CO2 during
      fermentation with immobilised yeast.

PMID- 14676984
TI  - Collective behaviour of crown channels.
AB  - Collective behaviour of a crown ether channel, bis[(benzo-15-crown-5)-15- yl
      methyl] pimelate, in a planar lipid bilayer membrane has been studied through
      electrophysiological methods. A characteristic feature of these channels is their
      sequential opening, indicated by a uniform stepwise increase in the multi-channel
      current. The experimental results show that there are three modes of relaxation,
      of which the slowest one is attributed to the channel-channel interaction. The
      latter varies with the number of channels incorporated in the bilayer membrane,
      leading to the interpretation that crown channels behave cooperatively.

PMID- 14676985
TI  - Congenital short-gut syndrome.
AB  - A case of congenital short gut is reported in a 4-month-old boy presenting with
      failure to thrive. Upper gastrointestinal examination (UGI) with small bowel
      follow-through (SBFT) demonstrated dilation of the duodenum and jejunum, with
      rapid transit to rectum. On barium enema (BE), rapid transit of barium was noted
      to the dilated proximal small bowel seen on UGI/SBFT. Neither study delineated
      the ileocecal region, and the overall length of bowel appeared short. The
      diagnosis of congenital short gut was confirmed at surgery. Congenital short-gut
      syndrome is a rare entity. The diagnosis can be suggested by imaging, but is
      usually confirmed operatively.

PMID- 14676987
TI  - Comparative metabolism of the designer drug 4-methylthioamphetamine by
      hepatocytes from man, monkey, dog, rabbit, rat and mouse.
AB  - Several cases of death associated with 4-methylthioamphetamine (4-MTA) have
      raised public concern about the abuse of this designer drug that is usually sold
      as "Ecstasy" or "Flatliners". Since only very little is known about the
      metabolism of 4-MTA in humans we performed an in vitro study incubating racemic 4
      MTA with primary hepatocytes isolated from three male human donors. Additionally,
      hepatocytes from male monkey (Cynomolgus), dog (Beagle), rabbit (Chinchilla), rat
      (Sprague-Dawley), and mouse (CD1) were examined for the metabolism of racemic 4
      MTA. We observed that 4-MTA was not extensively metabolised by hepatocytes from
      all species examined. The main metabolite was identified as 4-methylthiobenzoic
      acid which, for the first time has been described as a human metabolite. In
      addition to metabolism we also examined 4-MTA-induced toxicity as evidenced by
      the ATP cellular content. Interestingly, one of the three human donors showed a
      dramatically increased sensitivity to the reduction in ATP content induced by 4
      MTA. Comparing the species examined, the most extensive formation of 4
      methylthiobenzoic acid was observed in the rabbit hepatocytes followed by human,
      monkey, dog and mouse hepatocytes, whereas no formation of 4-methylthiobenzoic
      acid was seen in the rat hepatocytes. Toxicity data suggest that rabbit
      hepatocytes are more resistant to 4-MTA than the other species, which may be due
      to the more extensive metabolism. In conclusion, we have shown that 4
      methylthiobenzoic acid is the main metabolite formed from 4-MTA by human
      hepatocytes and also by the hepatocytes of the other tested species except the
      rat. Toxicity data suggest only moderate interspecies differences.

PMID- 14676988
TI  - Purification of saliva agglutinin of Streptococcus intermedius and its
      association with bacterial aggregation and adherence.
AB  - Streptococcus intermedius strain 1208-1 cells were aggregated in the presence of
      saliva. The saliva agglutinin was purified by centrifugation, filtration, and gel
      filtration. SDS-PAGE analyses indicated that the purified agglutinin consisted of
      two high-molecular-mass proteins. Aggregation was dependent on calcium over pH
      5.5, with 1 mM being the most effective concentration. Boiling inactivated
      purified agglutinin. S. intermedius strain 3 and Streptococcus mutans strain 1
      were aggregated in the purified agglutinin. After adsorption with strain 1208-1
      cells, the saliva sample did not exhibit any aggregation activity, and the
      agglutinin bands were no longer visible by SDS-PAGE. Adherence analyses
      demonstrated that the purified agglutinin immobilized on the surfaces of
      polystyrene wells, actinomyces cells, and apatite beads accounted for the binding
      of streptococcus cells. Agglutinin also effectively inhibited adherence to
      apatite beads coated with native saliva.

PMID- 14676989
TI  - Mutation analysis of the different tfd genes for degradation of chloroaromatic
      compounds in Ralstonia eutropha JMP134.
AB  - Ralstonia eutropha JMP134 possesses two sets of similar genes for degradation of
      chloroaromatic compounds, tfdCDEFB (in short: tfdI cluster) and tfdDII CII EII
      FII BII (tfdII cluster). The significance of two sets of tfd genes for the
      organism has long been elusive. Here, each of the tfd genes in the two clusters
      on the original plasmid pJP4 was replaced by double recombination with a gene
      fragment in which a kanamycin resistance gene was inserted into the respective
      tfd gene's reading frame. The insertion mutants were all tested for growth on 2,4
      dichlorophenoxyacetic acid (2,4-D), 2-methyl-4-chlorophenoxyacetic acid (MCPA),
      and 3-chlorobenzoate (3-CBA). None of the tfdDII CII EII FII BII genes appeared
      to be essential for growth on 2,4-D or on 3-CBA. Mutations in tfdC, tfdD and tfdF
      also did not abolish but only retarded growth on 2,4-D, indicating that they were
      redundant to some extent as well. Of all tfd genes tested, only tfdE and tfdB
      were absolutely essential, and interruption of those two reading frames abolished
      growth on 2,4-D, 3-CBA ( tfdE only), and MCPA completely. Interestingly, strains
      with insertion mutations in the tfdI cluster and those in tfdDII, tfdCII, tfdEII
      and tfdBII were severely effected in their growth on MCPA, compared to the wild
      type. This indicated that not only the tfdI cluster but also the tfdII cluster
      has an essential function for R. eutropha during growth on MCPA. In contrast,
      insertion mutation of tfdDII resulted in better growth of R. eutropha JMP134 on 3
      CBA, which is most likely due to the prevention of toxic metabolite production in
      the absence of TfdDII activity.

PMID- 14676990
TI  - Molecular characteristics and transcription of the gene encoding a
      multifunctional alcohol dehydrogenase in relation to the deactivation of pyruvate
      formate-lyase in the ruminal bacterium Streptococcus bovis.
AB  - To clarify the deactivation mechanism of pyruvate formate-lyase (PFL) and its
      role in the regulation of fermentation in Streptococcus bovis, the molecular
      properties and genetic expression of multifunctional alcohol dehydrogenase (ADHE)
      were investigated. S. bovis was found to have ADHE, which was deduced to consist
      of 872 amino acids with a molecular mass of 97.4 kDa. The ADHE was shown to
      harbor three enzyme activities: (1) alcohol dehydrogenase, (2) coenzyme-A-linked
      acetaldehyde dehydrogenase that catalyzes the conversion of acetyl-CoA to
      ethanol, and (3) PFL deactivase. Similar to Escherichia coli ADHE, S. bovis ADHE
      required Fe2+ for its activity. The gene encoding ADHE ( adhE) was shown to be
      monocistronic. The level of adhE mRNA changed in parallel with the mRNA levels of
      the genes encoding PFL (pfl) and PFL-activating enzyme (act) as the growth
      conditions changed, although these genes are independently transcribed. Synthesis
      of ADHE, PFL-activating enzyme, and PFL appears to be regulated concomitantly.
      Overexpression of ADHE did not cause a change in the formate-to-lactate ratio. It
      is conceivable that ADHE is not significantly involved in the reversible
      inactivation of active PFL under anoxic conditions. Partition of the flow from
      pyruvate appears to be mainly regulated by the activities of lactate
      dehydrogenase and PFL.

PMID- 14676991
TI  - Risk assessment and screening for low bone mineral density in a multi-ethnic
      population of women and men: does one approach fit all?
AB  - Screening for osteoporosis is currently recommended for all women aged 65 years
      and older in the USA. How to address screening of non-white women and all men is
      unclear. Osteoporosis risk assessment questionnaires have been designed and
      tested mostly among postmenopausal white women, and there is a lack of consensus
      on appropriate bone mineral density (BMD) cut-off values for defining
      osteoporosis in non-white persons. The objectives of the present study were to
      identify a set of risk factors from published population-based studies in white
      women and men and determine the ability of these risk factors to predict
      osteoporosis and low BMD in African-American (AA), Mexican-American (MA), and
      white women and men, and to assess the diagnostic accuracy of this set of risk
      factors for identifying osteoporosis separately in AA, MA, and white women and
      men by the use of data for 2,590 women and 2,391 men 50-79 years of age from the
      third National Health and Nutrition Examination Survey (NHANES III). We employed
      the World Health Organisation (WHO) definition of osteoporosis, using race/ethnic
      and gender-specific young adult mean values when calculating the T scores. Low
      body-mass index, low calcium intake, current cigarette smoking, and physical
      inactivity were independent risk factors identified from population-based
      studies. The presence of one or more risk factors was associated with having
      osteoporosis and low BMD in all groups. The strength of these associations was
      greater when two or more risk factors were present but varied with
      race/ethnicity, gender, and age. We conclude that this set of osteoporosis risk
      factors predicts osteoporosis in non-white women and men. Furthermore, as a risk
      assessment tool, this set of risk factors might be useful for reducing the number
      of unnecessary BMD tests performed in older women as well as identifying non
      white men who do not require BMD testing.

PMID- 14676992
TI  - The effect of 1-year transdermal estrogen replacement therapy on bone mineral
      density and biochemical markers of bone turnover in osteopenic postmenopausal
      systemic lupus erythematosus patients: a randomized, double-blind, placebo
      controlled trial.
AB  - We studied the effect of 1-year transdermal estrogen replacement therapy (ERT) on
      bone mineral density (BMD) and biochemical markers of bone turnover in osteopenic
      postmenopausal systemic lupus erythematosus (SLE) patients in a randomized,
      double-blind, placebo-controlled trial. SLE patients were randomly allocated to
      treatment (estradiol; 50 microg transdermal 17beta-estradiol; n=15) or placebo (
      n=17) group. Both groups received 5 mg continuous oral medroxyprogesterone
      acetate, 500 mg calcium and 400 IU vitamin D(3). L(1)-L(4) spine (LS), left femur
      and total hip BMD were measured at baseline and at 6 and 12 months. Serum
      osteocalcin (OC) and degradation products of C-terminal telopeptides of type-I
      collagen (CTx) levels were measured at baseline and 3, 6, 9, and 12 months. There
      was a significant difference in the percentage change of LS BMD at 6 months
      between the two groups (103.24+/-3.74% (estradiol group) vs 98.99+/-3.11%
      (placebo group); P<0.005). There was a significant decrease within the estradiol
      group in the CTx levels between baseline and all subsequent visits ( P<0.05).
      There was no significant difference in SLE disease activity index, Systemic Lupus
      International Collaborating Clinics/American College of Rheumatology (ACR) damage
      index and corticosteroid dose during the study period. Transdermal estradiol may
      prevent bone loss in postmenopausal SLE women at the lumbar spine and femur, with
      no increase in disease activity among postmenopausal SLE women receiving
      transdermal ERT. The high dropout rate (8/15) leads us to the conclusion that
      efficacy of HRT in a high-risk group such as SLE women can be attained only in a
      small number of patients, provided all inclusion/exclusion criteria are strictly
      adhered to.

PMID- 14676993
TI  - The orthopaedic surgeon's role in diagnosing and treating patients with
      osteoporotic fractures: standing discharge orders may be the solution for timely
      medical care.
AB  - Patients who suffer osteoporotic fractures do not typically receive
      medical/pharmaceutical treatment for osteoporosis. Orthopedic surgeons are
      concerned about, but not always diligent in following up on, the medical
      treatment of their fracture patients. The objective of this study was to
      determine whether orthopedic surgeons could effectively and consistently refer
      patients with osteoporotic fractures to a primary care provider (PCP) for
      possible work-up and treatment of osteoporosis. Fourteen orthopedic surgeons
      participated in the program. Sixty-nine qualifying patients were >/=50 years old,
      had a low-energy fracture, and had no prior treatment for osteoporosis. For each
      patient, two letters requesting a PCP appointment were sent to their PCP: one
      within 10 days of fracture and another 3-10 weeks after fracture. Patients were
      also instructed that they might have osteoporosis, and were directed to see their
      PCP. Results showed that of 69 patients (59 females, ten males: average age
      69.5+/-10.9 years), 30 (43.5%) did not see a PCP within 84 days. Thirty-nine
      (56.5%) patients saw a PCP within 84 days, but osteoporosis was not addressed in
      four (average days to PCP, 39.8+/-18.6: range 7-78 days). Of patients seen within
      84 days, anti-resorptive medications (e.g. bisphosphonate) were started in 21/39
      (53.8%), but typically not within 41 days of fracture. Of the 14 orthopedic
      surgeons, five were non-compliant and seven were inconsistent in their
      participation, forgetting to send the letters and/or inform patients to make PCP
      appointments. Standing discharge orders (for medications, PCP follow-up, bone
      density scanning, etc.) may be more effective in achieving timely medical
      treatment for patients of orthopedic surgeons with osteoporotic fractures.

PMID- 14676994
TI  - The use and misuse of prosthetic materials in reconstructive pelvic surgery: does
      the evidence support our surgical practice?

PMID- 14676995
TI  - Innovations in pharmacotherapy for stress urinary incontinence.
AB  - The purpose of this review article is to highlight new pharmacotherapies on the
      horizon for the treatment of stress urinary incontinence (SUI). Although
      behavioral and surgical therapies are currently the mainstay of treating SUI, we
      believe that medications will take center stage and possibly become first-line
      therapy. Currently, there are no FDA medications indicated for SUI. However,
      results are becoming available about an oral medication, duloxetine, which
      appears to be clinically safe and efficacious for the treatment of SUI. In
      addition to discussing medications currently under development, we will also
      discuss exciting pharmacological targets that could be suitable to treat SUI.

PMID- 14676996
TI  - Transurethral delivery of radiofrequency energy for tissue micro-remodeling in
      the treatment of stress urinary incontinence.
AB  - This initial human study was performed to determine the safety and quality of
      life impact of transurethral radiofrequency energy (RFe) tissue micro-remodeling
      of the proximal urethra and bladder outlet in patients with stress urinary
      incontinence (SUI). Forty-one patients with SUI were sequentially enrolled into
      four treatment groups and then underwent rapid outpatient treatment under
      conscious sedation using an investigational RFe delivery device. The device is
      passed through the urethra and palpably positioned by the anchoring of a balloon
      within the bladder outlet. Four small needle electrodes are deployed into the
      proximal urethra and/or bladder outlet submucosa, and RFe is delivered. No
      patient has suffered a serious adverse event in 6 months of follow-up. At 6
      months, 75%-80% of patients in all four groups have demonstrated an improvement
      in quality of life. Two groups demonstrated statistical significance in both mean
      quality of life improvement and incontinence frequency reduction at 6 months.

PMID- 14676997
TI  - Correlation of perineal ultrasound and lateral chain urethrocystography in the
      anatomical evaluation of the bladder neck.
AB  - Although perineal ultrasound has been widely used, no standard values have been
      published. In 52 women with urinary stress incontinence the following parameters
      were measured during resting and straining: a) with ultrasound: distance (Dy)
      between bladder neck and central line of the symphysis, distance (Dx) between
      bladder neck and lower border of the symphysis, and retrovesical angle beta; b)
      with urethrocystography (UCG): distance H between the bladder neck and the SCIPP
      line, inclination angle alpha and retrovesical angle beta. Dy and H correlated
      during resting ( r = 0.608; p<0.001) and straining ( r = 0.575; p<0.001). The
      distance Dy of 11 mm corresponded to a bladder neck position on the SQIPP line. A
      rotational descent was detectable when Dx increased from 13 mm (+/- 6.5) during
      resting to 16 mm (+/-7.8) during straining ( p=0.009). It was concluded that
      perineal ultrasound is valuable for the anatomical evaluation of the bladder
      neck. This is the first report to better define the position of the bladder based
      on ultrasonographic measurements.

PMID- 14676998
TI  - Effect of a new guideline on outcome following third-degree perineal tears:
      results of a 3-year audit.
AB  - The aim of this study was to assess the impact of a new guideline on the outcome
      of repair of obstetric anal sphincter tears by examining adherence to the
      guideline and the effect upon the incidence of symptoms of anal incontinence. An
      audit of third-degree perineal tears was conducted in 1997. A reaudit was
      completed in 1998 and 1999 after the introduction of a new guideline. The audits
      were conducted in a tertiary obstetric unit with 5000 deliveries per annum. Over
      the 3-year period between 1997 and 1999 124 women with a third-degree tear were
      identified; 14 381 women who had delivered vaginally without third-degree tears
      were used as controls. The main outcome measure was the number of cases with
      adherence to the protocol, and the number of patients with ongoing symptoms.
      Cases were identified from the hospital database, and case notes were reviewed to
      obtain clinical data. The incidence of third-degree perineal tears was 0.81% over
      the 3-year period. Following the introduction of a new guideline there was a
      significant increase in the number of repairs performed in theatre (70% vs 82% vs
      97%, P<0.05), using Prolene (64% vs 76% vs 93%, P< 0.05), with adequate
      anesthesia (70% vs 82% vs 97%, P<0.05). At follow-up there was a transient
      improvement in defecatory symptoms in the first year of the protocol only (45% vs
      32% vs 50%, P<0.01). More patients had complete follow-up data after introduction
      of the protocol: 66% vs 86% vs 80% ( P<0.001). There were more cases of Prolene
      suture migration (7% vs 34% vs 16%, P<0.01). We concluded that the introduction
      of a new guideline was followed by improved performance of appropriate repair.
      There was no sustained improvement in fecal symptoms at follow-up.

PMID- 14676999
TI  - The effect of tension-free vaginal tape (TVT) procedure on sexual function in
      women with stress urinary incontinence.
AB  - The aim of this study was to evaluate the effects of tension-free vaginal tape
      (TVT) on sexual function in women with stress urinary incontinence (SUI) by
      questionnaire. Thirty-two sexually active and married women who were planned for
      TVT to treat SUI constituted the patient group, and 25 women who were healthy,
      sexually active and married, were selected as the control group; the ages of both
      groups matched. Sexual functions (desire, arousal, orgasm, pain and satisfaction)
      were evaluated with the Index of Female Sexual Function (IFSF), and continence
      status during sexual intercourse was asked about both preoperatively and
      postoperatively in the 6th month. The mean domain scores of sexual functions such
      as desire, arousal, orgasm, pain and overall satisfaction preoperatively and
      postoperatively were 3.37+/-0.69, 3.82+/-0.62, 3.40+/-0.95, 3.41+/-0.98, 3.16+/
      1.09 and 3.32+/-0.79, 3.71+/-0.53, 3.06+/-1.04, 2.75+/-1.29, 2.88+/-0.63,
      respectively, and postoperative scores insignificantly decreased. Also, these
      scores in the control group were 3.64+/-0.66, 3.96+/-0.73, 4.12+/-0.78, 3.96+/
      1.14 and 3.68+/-0.92. In comparison with the control group, whereas all of the
      preoperative domain scores were found to be decreased but were statistically
      insignificant except orgasmic function, postoperative scores significantly
      worsened, except for desire and arousal. However, preoperatively nine patients
      explained that they had incontinence during sexual intercourse, and this problem
      persisted in two postoperatively ( p = 0.043). This study shows that both SUI and
      the TVT procedure negatively affect sexual function in women.

PMID- 14677000
TI  - How does tension-free vaginal tape correct stress incontinence? investigation by
      perineal ultrasound.
AB  - Forty patients who underwent a single tension-free vaginal tape procedure were
      evaluated by perineal ultrasound both pre- and postoperatively in a prospective
      observational clinical study. The positions of the tape, bladder neck and urethra
      were sonographically documented at rest and during Valsalva maneuvers. During
      Valsalva the tape rotated towards the symphysis in all patients. Postoperative
      urethral angulation could be demonstrated in 36 of 40 patients. Bladder neck
      mobility remained unchanged after the tension-free vaginal tape procedure, and 36
      of the 40 were dry according to patient questionnaires. Postoperative cough test
      was negative in all patients. Two points seem to be important for the functioning
      of the tension-free vaginal tape: a dynamic kinking of the urethra during stress,
      and the movement of the tape against the symphysis, compressing the tissue
      between the tape and the symphysis. Mobility of the bladder neck is unaffected by
      the single tension-free vaginal tape procedure.

PMID- 14677001
TI  - Vaginal wind - a new pelvic symptom.
AB  - The aim of this study was to evaluate the risk factors, investigations and
      treatments for vaginal wind. A prospective longitudinal study was carried out at
      a tertiary care referral centre at St George's Hospital, London. Six consecutive
      women with symptomatic vaginal air were enrolled in the study, which used a
      comprehensive questionnaire for vaginal air, prolapse, urinary, bowel and sexual
      symptoms, vaginal examination following the Standardized ICS Scoring System for
      prolapse, physiotherapist evaluation, and analysis of the treatment. Main outcome
      measures were the effect of the patient's age, weight, parity, mode of delivery,
      fetal weight, and the treatment (conservative and surgical) on the frequency of
      vaginal wind. The mean age of the six women was 32.8+/-9.9 years (range 21-52),
      the mean BMI was 23.1+/-5.5 (range 15.2-32.2), all women were premenopausal and
      five were parous. The mean estimated frequency of the symptoms was 20.0+/-8.1 per
      day (range 10-40). All the patients completed a course of pelvic floor
      physiotherapy and one patient had a posterior repair and later a Fenton operation
      without improvement. A modified 'Bard' pessary was the main form of treatment and
      resolved the symptoms in two women. Vaginal wind causes significant distress and
      embarrassment to sufferers. Further information on risk factors, evaluation and
      treatment modalities should be obtained.

PMID- 14677002
TI  - A retrospective claims analysis of the direct costs of stress urinary
      incontinence.
AB  - The aim of this study was to evaluate direct expenditures associated with urinary
      incontinence and overall medical expenditures incurred by women diagnosed with
      stress urinary incontinence (SUI). The study design was a retrospective analysis
      of administrative claims data. We identified women with a diagnosis of SUI and no
      stress, urge or mixed urinary incontinence in the preceding 12 months using the
      MarketScan 1996-1999 databases. Total expenditures, as well as urinary
      incontinence-related expenditures, were summarized during the 12 months before
      and after the initial SUI diagnosis. We also compared expenditures for SUI
      patients receiving surgical treatment to expenditures for those who did not.
      There were 8126 patients who met the eligibility criteria. Total healthcare
      expenditures in the year prior to the initial SUI diagnosis were approximately
      half of those in the year following the initial diagnosis ($4478 vs $9147). For
      the subset of patients treated with surgery there was a threefold increase ($4575
      vs $14129) in costs. A sensitivity analysis in patients with no comorbid urinary
      diagnoses found somewhat lower costs but a similar rate of increase in costs
      between the pre-period and the study period ($3884 vs $7075). Among women with no
      comorbid urinary diagnoses, approximately 11% ($769; SD $1180) of total mean
      regression-adjusted annual expenditures ($6892; SD $5067) was attributable to UI.
      Predicted total expenditures for surgery patients without comorbid urinary
      diagnoses were $13 212 (SD $7967), 28% of which ($3640;SD $681) were for UI
      related costs. We concluded that after diagnosis, annual expenditures for
      patients were roughly twice those in the year prior to diagnosis. Multivariate
      analysis suggests that in the year after SUI diagnosis, UI treatment costs
      represented approximately 10% of total expenditures for all SUI patients, and 26%
      28% of total expenditures for the subset of surgically treated patients.

PMID- 14677003
TI  - The Contiform incontinence device - efficacy and patient acceptability.
AB  - A consecutive series of 59 women with urodynamic stress incontinence but no
      prolapse were offered treatment with Contiform (available in small/medium/large
      sizes). The 24-h pad test was the primary outcome measure. Of the 59 enrolled
      women, 41 (69%) completed the trial protocol. Median use was 21 days (IQR 10
      24.5). Two severity groups were categorized based on pretreatment pad testing
      (mild <30 g/day n=24 patients, 59%) and moderate/severe >30 g/day, n= 17(41%).
      Overall, loss was reduced by a median of 72% (5-92), p<0.0001, with the greatest
      reduction seen in the moderate/severe group of 85% (75-100) p<0.0001. No
      significant benefit on pad testing was noted in the mild group. Both groups
      showed significant benefit on the Incontinence Impact Questionnaire. The
      insertion technique was quickly learnt and the device well tolerated. A medium
      sized Contiform was used by 33 (80%) women. No serious adverse events occurred.

PMID- 14677004
TI  - The impact of hysterectomy on lower urinary tract symptoms.
AB  - The aim of this study was to prospectively evaluate the effect of vaginal and
      abdominal hysterectomy on lower urinary tract symptoms. We interviewed 120
      patients undergoing hysterectomy for benign conditions preoperatively using a
      standardized questionnaire. At 6.6 and 12.7 months, 119/120 and 115/120 patients
      completed the follow-up questionnaire. Forty-four patients underwent vaginal and
      76 abdominal hysterectomy. At 6 months follow-up there was a decrease ( p<0.05)
      in symptoms of stress urinary incontinence in the abdominal cohort, but this did
      not remain at 12 months' follow-up. There were no significant changes in symptoms
      of stress urinary incontinence in the vaginal cohort at either 6 or 12 months'
      follow-up. Postoperative micturition frequency was reduced in both cohorts. No
      significant differences were found regarding symptoms of urge urinary
      incontinence, urge complaints or voiding difficulties. The present study does not
      support the assumption that abdominal or vaginal hysterectomy is associated with
      de novo or deteriorating symptoms of urinary incontinence.

PMID- 14677005
TI  - Treatment of overactive bladder with botulinum toxin type B: a pilot study.
AB  - The purpose of this study was to determine the efficacy and safety of botulinum
      toxin type B (BTX-B/Myobloc) in the treatment of patients with overactive
      bladder. This open-label dose-escalation study enrolled 15 female patients with
      urinary frequency with or without incontinence. The BTX-B doses used in this
      study were 2500, 3750, 5000, 10 000 and 15 000 units. Response was defined as a
      subjective improvement in frequency, urgency and incontinence symptoms. A paired
      t-test of the pre/post frequency difference indicates that these 15 patients
      experienced an average of 5.27 fewer frequency episodes per day after treatment
      with BTX-B. The p value for the paired t-test was <0.001. The longest duration
      effect was 3 months using 10 000-15 000 units of BTX-B. The correlation between
      dose and duration was very significant, with a correlation coefficient = 0.96,
      p<0.001. Based on these findings, we feel the use of botulinum toxin to treat
      patients with overactive bladder warrants further study.

PMID- 14677006
TI  - Accuracy of cystoscopy in the diagnosis of ureteral injury in benign gynecologic
      surgery.
AB  - Our objective was to review our experience and attempt to identify risk factors
      for ureteral injury during gynecologic surgery for benign conditions. A
      retrospective chart review was performed of all cases of ureteral injury during
      gynecologic surgery for benign conditions, at Temple University Hospital, from
      January 1992 to September 2002. We analyzed hospital records to determine whether
      the injury was diagnosed intraoperatively, with postprocedure cystoscopy, or if
      cystoscopy was ineffective in diagnosing the injury. There were nine ureteral
      injuries during the study period. Of these, two were diagnosed during the
      procedure, two were discovered by immediate postprocedure cystoscopy, and the
      other five were discovered during the postoperative period. Of these five, three
      patients had immediate postprocedure cystoscopy and the injuries were not
      detected. Risk factors associated with ureteral injury included: a large uterus
      (5), high-grade cystocele (3), ectopic insertion of the ureter into the bladder
      (1), and previous surgeries (4). Our conclusion was that negative cystoscopy
      cannot be solely relied on to rule out ureteral injury, as cases with partial
      obstruction and ureteral patency can be missed.

PMID- 14677007
TI  - A randomized comparison between monofilament and multifilament tapes for stress
      incontinence surgery.
AB  - Our objective was to compare monofilament and multifilament tapes positioned
      without tension at the midurethra for postoperative complications and cure rate.
      One hundred patients with stress urinary incontinence were randomly allocated
      into two study groups. Using identical surgical methodology, 50 patients had a
      monofilament tape inserted at the midurethra using the TVT delivery instrument,
      and another 50 a multifilament tape using the IVS delivery instrument. The only
      significant difference between the groups was in the incidence of postoperative
      urinary retention ( p=0.023). Ten patients from the monofilament group required
      longer than normal ('normal' means to the morning of the next day)
      catheterization, in contrast to only two from the multifilament group. The
      clinical efficacy of both procedures was equally high. Conclusions were that both
      tapes appear to be equally effective in the surgical treatment of SUI. The higher
      incidence of postoperative urinary retention in the monofilament group was most
      likely caused by the elastic feature of this tape.

PMID- 14677009
TI  - Patterns of pain in Paget's disease of bone and their outcomes on treatment with
      pamidronate.
AB  - Two-thirds of patients with Paget's disease seeking medical attention present
      with pain. We studied patterns of pagetic pain in relation to physical activity,
      and the effect of coexistent osteoarthritis (OA)/pagetic arthropathy on pain and
      physical activity before and after treatment with pamidronate. Patients with
      lower-segment Paget's disease (lumbar spine, pelvis or lower limbs), raised
      alkaline phosphatase (ALP), and pain as a symptom were included. Two subgroups
      were identified based on the absence (P group), or presence (POA group) of
      radiological OA in the lower segment. They received 2-4 fortnightly infusions of
      pamidronate 30-60 mg and were followed up at 6 weeks, 3 months and 6 months.
      Outcome measures were visual analog scales for pain at rest, on standing, on
      walking and at night; standing time, walking distance, 50-yard walking time, and
      ALP. Twenty-five patients (12 men, 13 women, mean age 70.1+/-1.9 years), received
      a mean of 142+/-9.7 mg of pamidronate. The P group had higher mean ALP (p=0.003)
      and higher scores for pain (not significant) at baseline than the POA group.
      Compared to baseline, P group had significant improvements (p<0.01) at 6 months
      in rest pain, standing pain and walking pain. The POA group had non-significant
      changes in pain at 6 months. ALP improved significantly at 6 months in both
      subgroups (p<0.01). The whole group also improved at 6 months in standing time
      (55.7%, not significant), walking distance (33.9%, not significant), and 50-yard
      walking time (24.2%, p<0.05). Paget's patients with coexistent joint disease had
      less severe pain and bone disease at baseline than those without coexistent joint
      disease, and responded less well to pamidronate, although they did have
      significant improvement in ALP levels. Radiographic assessment for coexisting
      joint disease prior to treatment might improve prognostication from the patient's
      point of view, and improve treatment compliance.

PMID- 14677008
TI  - Efficacy of cyclophosphamide combined with prednisolone in patients with AA
      amyloidosis secondary to rheumatoid arthritis.
AB  - Secondary amyloid A (AA) amyloidosis is an uncommon yet important complication of
      rheumatoid arthritis (RA). It is one of the most relentless of the extra
      articular features of RA, and suitable treatments have not yet been found. We
      studied the efficacy of cyclophosphamide (CYC) combined with prednisolone (PSL)
      in amyloidotic patients who had serum amyloid A (SAA) 1.3 genotype, which is a
      risk factor for secondary amyloidosis in Japanese RA patients. Fifteen RA
      patients who were SAA1.3 homo- and heterozygotes with biopsy-confirmed AA
      amyloidosis were treated with a combination of CYC and PSL. Laboratory variables
      of C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation
      rate (ESR), serum albumin (Alb), serum creatinine (Cre) and Lansbury's index were
      carried out by statistical analysis of changes between before and during the
      medication. According to the Mann-Whitney rank test, CRP, RF, ESR, Alb and Cre
      levels improved significantly with the combination treatment (p<0.05). Also,
      paired t-tests showed significance in Lansbury's index between before and during
      the medication (p=0.007). CYC combined with PSL ameliorated not only laboratory
      markers but also clinical rheumatoid activity in patients with amyloidosis
      secondary to RA, whose genotypes were SAA1.3 homo- and heterozygous. CRP, ESR,
      RF, Alb and Cre will be surrogate markers of therapeutic efficacy. The
      combination of CYC and PSL appears to be beneficial for Japanese RA patients who
      are SAA1.3 homo- and heterozygous carriers, associated with secondary AA
      amyloidosis.

PMID- 14677010
TI  - Joint symptoms and diseases associated with moisture damage in a health center.
AB  - Rheumatic diseases do not usually cluster in time and space. It has been proposed
      that environmental exposures may initiate autoimmune responses. We describe a
      cluster of rheumatic diseases among a group of health center employees who began
      to complain of symptoms typically related to moldy houses, including
      mucocutaneous symptoms, nausea and fatigue, within a year of moving into a new
      building. Dampness was found in the insulation space of the concrete floor below
      ground level. Microbes indicating mold damage and actinobacteria were found in
      the flooring material and in the outer wall insulation. The case histories of the
      personnel involved were examined. All 34 subjects working at the health center
      had at least some rheumatic complaints. Two fell ill with a typical rheumatoid
      factor (RF)-positive rheumatoid arthritis (RA), and 10 had arthritis that did not
      conform to any definite arthritic syndrome (three met the classification criteria
      for RA). Prior to moving into the problem building one subject had suffered
      reactive arthritis, which had then recurred. Another employee had undiagnosed
      ankylosing spondylitis and later developed psoriatic arthritis, and another
      developed undifferentiated vasculitis. A total of 16 subjects developed joint
      pains, 11 of these after beginning work at the health center. Three subjects
      developed Raynaud's symptom. Fourteen cases had elevated levels of circulating
      immune complexes in 1998, 17 in 1999, but there were only three cases in 2001,
      when the health center had been closed for 18 months. The high incidence of joint
      problems among these employees suggests a common triggering factor for most of
      the cases. As some of the symptoms had tended to subside while the health center
      was closed, the underlying causes are probably related to the building itself and
      possibly to the abnormal microbial growth in its structures.

PMID- 14677011
TI  - Septic arthritis following intra-articular steroid injection of the knee--a
      survey of current practice regarding antiseptic technique used during intra
      articular steroid injection of the knee.
AB  - Septic arthritis is a potential catastrophic complication of intra-articular
      steroid injection. There is lack of evidence regarding the precautions that
      should be taken to avoid such a complication, as well as how often it is
      encountered. The aim of this study was to evaluate the antiseptic precautions
      taken during intra-articular steroid injection of the knee in the United Kingdom
      (UK), and estimate how often septic arthritis is encountered by health
      professionals in the UK following steroid injection of the knee. A questionnaire
      was posted to 100 orthopaedic surgeons, 100 rheumatologists and 50 general
      practitioners (GPs), asking them about the cases of septic arthritis following
      intra-articular steroid injection of the knee that they encountered during their
      practice and the precautions they take when injecting knees. The response rate
      was 76.4%; 57.6% of the respondents used alcohol swabs to clean the skin, and the
      remaining 42.4% used chlorhexidine or Betadine. Only 16.3% used sterile towels to
      isolate the injection site. There were 32.5% of respondents who routinely used
      sterile gloves when injecting, and a total of 46.6% used either sterile or non
      sterile gloves. Also, 91.1% changed needles between drawing the steroid and
      injecting it into the joint. Only 24 respondents (12.6%) had encountered septic
      arthritis after steroid injection of the knee (18 once, 3 twice, 2 three times, 1
      several times). We concluded that septic arthritis post intra-articular steroid
      injection of the knee is probably rare. There is a wide variation in the
      precautions taken to avoid such a complication. However, the trend seems to be
      towards minimal use of antiseptic techniques. Further large prospective studies
      are needed to determine how frequently septic arthritis of the knee is
      encountered post steroid injection, and the exact precautions that should be
      taken to avoid it.

PMID- 14677012
TI  - Sonography detection threshold for knee effusion.
AB  - The aim of this study was to determine the threshold for detecting knee effusion
      by ultrasound (US). Five knee specimens from embalmed cadavers were studied.
      Intra-articular injection of saline, blood and synovial fluid was performed under
      ultrasound control and methylene blue dye instillation. The smallest amount of
      fluid detectable by US in the knee was 7.4 ml for synovial fluid, 10.1 and 10.4
      ml for saline solution and 9.7 for blood. The threshold for detecting knee joint
      effusion by US in cadaver specimens was 10 ml for saline and blood and 7 ml for
      synovial fluid.

PMID- 14677013
TI  - Low-dose intravenous cyclophosphamide in systemic sclerosis: a preliminary safety
      study.
AB  - Both oral and intravenous high-dose cyclophosphamide (CYC) regimens are
      associated with serious side effects when used for the treatment of systemic
      sclerosis (SSc). The aim of the present trial was to test the safety of low-dose
      intravenous CYC in patients with SSc. Eight SSc patients, in whom CYC treatment
      was warranted, were studied at baseline and after 6 months' intravenous CYC
      treatment (500 mg pulses at weeks 0, 1, 2, 6, 10, 14, 18 and 22). Side effects
      probably related to CYC treatment were carefully investigated. The development of
      amenorrhea was assessed during the period of treatment and over the following 12
      months. The therapy was well tolerated overall. No patient discontinued treatment
      because of side effects. Leukopenia, premature ovarian failure, hemorrhagic
      cystitis, microscopic hematuria and liver toxicity were never detected. The most
      common adverse events were mild and self-limiting nausea and weakness. Our data
      suggest that low-dose intravenous CYC is relatively safe, at least in the short
      term. Further studies are needed to assess both the efficacy and the long-term
      safety.

PMID- 14677014
TI  - Synovial fluid nitric oxide levels in patients with knee osteoarthritis.
AB  - Nitric oxide (NO) has an important role in the inflammatory arthropathies. This
      study investigated NO levels in the synovial fluid and plasma of patients with
      primary osteoarthritis (OA) of the knee. Twenty-seven cases with primary knee OA
      and 13 controls were recruited for the study. Nitrate/nitrite levels of synovial
      fluid and plasma were measured by Griess reaction, and interleukin-1 beta (IL-1
      beta) levels were measured quantitatively by a sandwich immunoassay technique. We
      found a significant increase in the synovial fluid nitrate/nitrite levels in
      cases with primary OA of the knee compared to controls (50.26+/-23.63 microg/l vs
      32.49+/-10.05 microg/l, p=0.002) as well as increased plasma nitrate/nitrite
      levels (57.06+/-23.32 microg/l vs 39.98+/-16.36 microg/l, p=0.012). There was no
      difference in plasma and synovial fluid IL-1 beta concentrations between the
      study and control groups. These results may be considered as supporting evidence
      that NO might be one of the factors responsible for cartilage destruction in
      primary osteoarthritis of the knee.

PMID- 14677015
TI  - Validation of the Spanish version of a screening questionnaire for the detection
      of systemic lupus erythematosus.
AB  - The aim of this study was to assess the sensitivity, specificity, positive and
      negative predictive values of the translation of a screening questionnaire for
      systemic lupus erythematosus (SLE) in Spanish-speaking populations. The
      questionnaire was applied to secondary-care outpatients in a rheumatology clinic.
      Sensitivity, specificity, predictive positive and negative values of the
      instrument, and the best cut-off point to discriminate between SLE patients and
      other conditions, were determined. Fifty-two subjects answered the questionnaire
      (21 patients with SLE, 15 with a possible diagnosis of SLE who eventually proved
      not to have the disease, and 16 healthy volunteers), which can be answered in 2
      min. The best cut-off point was three affirmative answers (95% specificity, 84%
      sensitivity, 80% predictive positive and 96% predictive negative values). The
      questionnaire can discriminate between SLE cases and other conditions.
      Sensitivity and specificity are close to those of the original English version.
      Applying this instrument can help to acquire informed estimates of SLE
      prevalence.

PMID- 14677016
TI  - Cardiac valvular disease in patients with systemic lupus erythematosus.
      Relationship with anticardiolipin antibodies.
AB  - We performed two-dimensional and Doppler echocardiography in 52 patients with
      systemic lupus erythematosus and in 34 healthy controls. In 25 patients (48.1%)
      echocardiographic disturbances were found (25/52 vs 2/34, p<0.001). Valvular
      abnormalities were detected in 18 patients (34.6%) but in only two controls
      (18/52 vs 2/34, p<0.01). The mitral valve was involved in 12 patients (23.1%).
      The most frequent finding was mild (13.5%) and moderate (9.6%) regurgitation or
      valvular thickening (9.6%). The aortic valve was involved in six and the
      tricuspid valve in three patients (11.5% and 5.8%, respectively). Only one
      patient had echocardiographic non-infective verrucous vegetation affecting the
      tricuspid valve. We did not observe significant hemodynamic valve disease.
      Endocardial findings were related to disease duration (p<0.05) but not to disease
      activity. Twenty-eight SLE patients (53.8%) had increased anticardiolipin
      antibodies (aCL). Patients with aCL (particularly those with IgG class) were
      characterized by a high incidence of echocardiographic abnormalities (p<0.001),
      mainly valvular (mitral or aortic) regurgitation (p<0.05). We found a
      relationship between anticardiolipin antibodies and disease activity (p<0.05). In
      conclusion, we postulate a prominent role for anticardiolipin antibodies in the
      pathogenesis of heart valve disease in patients with SLE.

PMID- 14677017
TI  - First carpometacarpal and interphalangeal osteoarthritis of the hand in patients
      with advanced hip or knee OA. Are there differences in the aetiology?
AB  - Differences in the aetiology of osteoarthritis (OA) of the first carpometacarpal
      joints (CMC-1) and the interphalangeal joints (IP) have been reported. It was the
      purpose of this investigation to evaluate whether isolated OA of the first
      carpometacarpal joints and the interphalangeal joints differs in its aetiology,
      considering potential risk factors such as age, gender, body mass index,
      occupational history, OA in the hip or knee joints, hypertension and diabetes in
      patients with advanced hip or knee OA. Included in this investigation were 639
      patients scheduled for either hip or knee replacement because of advanced OA. As
      well as a standardised interview and clinical examination, bilateral radiographs
      of both hands were obtained. According to the presence or absence of radiographic
      OA, participants were categorised as having CMC-1 OA (= 1 joint) or IP OA (= 2
      joints), either isolated or in combination. Odds ratios (OR) and their 95%
      confidence intervals (CI) for potential determinants of OA were estimated using
      multivariable logistic regression. Of the total number of patients, 184 had CMC-1
      OA and 424 IP OA. Patients with CMC-1 OA were more likely to be female (77.2%),
      and to have knee OA (62.5%) and hypertension (63.0%), than patients without CMC-1
      OA. No differences between CMC-1 OA and IP OA were observed for the role of age,
      body mass index and diabetes. Age was associated with both CMC and IP OA. Female
      gender was independently associated with CMC-1 OA (OR=1.79; 95% CI: 1.16-2.74)
      but not with IP OA. Our data suggest a possible impact of age and female gender
      on the aetiology of CMC-1 OA and of age on IP-OA, at least in patients with
      advanced hip or knee OA.

PMID- 14677019
TI  - The effect of hand osteoarthritis on grip and pinch strength and hand function in
      postmenopausal women.
AB  - The aim of the study was to investigate the effect of osteoarthritis on hand
      function in postmenopausal women. One hundred patients with hand OA and 70
      healthy volunteers as controls were evaluated. Grip and pinch strength
      measurements and Dreiser's functional index were used for hand function. Pain was
      assessed by a visual analog scale, and tenderness was assessed by palpation and
      scored, depending on the severity of tenderness, as 0, 1 or 2. Heberden's and
      Bouchard's nodules and joint involvement were also recorded. The number of
      patients with only distal interphalangeal joint involvement was 50 (50%), those
      with distal interphalangeal joint plus proximal interphalangeal joint involvement
      was 49 (49%), and those with carpometacarpal joint involvement numbered 18 (18%).
      The incidence of Heberden's and Bouchard's nodules was 85% and 36%, respectively.
      Eighty-six (86%) patients were suffering from pain and 57 were found to have
      tenderness. Grip and pinch strength was significantly lower (p<0.05) and
      Dreiser's functional index score was significantly higher (p<0.001) in the study
      group (particularly in grade 4 OA). Grip strength was lower in hand OA patients
      with distal interphalangeal joint plus proximal interphalangeal joint involvement
      than in those with only distal interphalangeal joint and carpometacarpal joint
      involvement. Pinch strength was also lower in patients with distal
      interphalangeal joint plus proximal interphalangeal joint plus carpometacarpal
      joint involvement. The patients with Heberden's and Bouchard's nodules had lower
      grip and pinch strength than controls. Also, pain and tenderness had significant
      (p<0.05) effects on hand function. Dreiser's total score ranged from 0 to 10 in
      80 (80%) patients and from 11 to 20 in 20 patients. In conclusion, hand
      osteoarthritis contributes to hand dysfunction, mainly related to the severity of
      osteoarthritis, pain, joint involvement and the presence of nodules.

PMID- 14677018
TI  - A study on soluble intercellular adhesion molecule-1 and selenium in patients
      with rheumatoid arthritis complicated by vasculitis.
AB  - Clinical manifestations of vasculitis, as a complication of rheumatoid arthritis
      (RA), can be postulated as a consequence of immune response abnormalities and
      endothelial cell dysfunction. In this study we searched for the relationship
      between the extent of vascular involvement and either serum sICAM-1 or selenium
      concentrations. We also explored the possible interaction of serum selenium with
      sICAM-1 to provide a greater understanding of their role in rheumatoid vasculitis
      (RV). For the study, we measured the serum titers of sICAM-1 using an ELISA assay
      and the serum selenium concentrations using the ETAAS method in 37 women
      suffering from RA and 18 normal women serving as controls. All the RA patients
      were evaluated by extensive clinical, laboratory and capillaroscopic studies. In
      all patients with extra-articular manifestations, severe or moderate changes in
      nailfold capillaroscopy were found. Serum sICAM-1 titers in RA patients with mild
      vasculitis on nailfold capillaroscopy did not differ significantly from those of
      the healthy subjects, whereas a higher sICAM-1 level seemed to reflect the more
      intensive vascular changes in capillaroscopy. These data suggest that sICAM-1
      serum levels may reflect the extent of the microvascular involvement in RA
      patients. Compared with controls, all the RA patients had markedly lower serum
      selenium concentrations, irrespective of the degree of the capillaroscopic
      vascular changes. A significant inverse correlation between sICAM-1 and selenium
      was found in the controls (r = -0.54; P<0.02). By contrast, no correlation was
      noted in RA patients (r=0.10, P not significant). This suggests that the sICAM-1
      shedding in RV does not appear to be influenced by selenium, presumably owing to
      its low serum concentration.

PMID- 14677020
TI  - Investigation of generalized osteoarthritis by combining X-ray grading of the
      knee, spine and hand using biochemical markers for arthritis in patients with
      knee osteoarthritis.
AB  - The aim of this study was to investigate generalized osteoarthritis (GOA) by
      combining X-ray grading of the knee, spine and hand using biochemical markers for
      arthritis, such as YKL-40 and urinary pyridinoline (Pyr). One hundred and thirty
      postmenopausal women with primary knee osteoarthritis (OA) aged 55-92 years were
      included. Knee X-rays were taken in all patients. Spinal X-rays and hand X-rays
      were taken in 101 and 102 patients, respectively, and both spine and hand X-rays
      were taken in 86 patients. The degree of OA was graded using the Kellgren
      Lawrence grading scale. Blood and urine were collected from all patients. Serum
      YKL-40 was measured using an ELISA kit and Pyr was measured using high
      performance liquid chromatography directly linked to an automated sample
      preparation with extraction columns system. The knee X-ray grades were most
      related to YKL-40 and Pyr. A combination of knee and spinal OA grades revealed a
      significant relation to changes in both YKL-40 and Pyr, and a combination of hand
      OA and knee OA grades to YKL-40. Although OA of the three joints was related to
      YKL-40, hand OA alone was not related to either of the biochemical markers. We
      concluded that Pyr and YKL-40 as biochemical markers of arthritis did not
      discriminate GOA defined by hand OA alone. Overall observation in the combination
      of three joint sites indicated that the site to discriminate GOA, from the most
      useful to the least, was the knee, the spine and the hand, and knee OA was the
      most closely related to Pyr and YKL-40.

PMID- 14677021
TI  - Selenium combined with vitamin E and vitamin C restores structural alterations of
      bones in heparin-induced osteoporosis.
AB  - The aim of this study was to investigate the effect of heparin on osteoporosis
      initiation, and the effect of selenium plus vitamins E and C, and the sole
      combination of vitamins E and C on the progress of osteoporosis induced by
      heparin through histologic means. Adult female New Zealand white rabbits were
      divided into three experimental and three control groups. The experimental
      rabbits were injected with 1000 IU/kg/day heparin (Liquemine) for 4 weeks. These
      six groups were administered deionized water (CI and EI), 100 mg/kg/day L
      ascorbic acid plus 100 mg/kg/day alpha-tocopherol acetate (CII and EII), and 0.05
      mg/kg/day sodium selenite, plus these vitamins orally, with a gastric catheter
      (CIII and EIII), respectively. At the end of the experimental period, the femurs
      of the animals were collected and investigated under a light photomicroscope.
      Heparin caused important alterations in bone, such as an improper lamellar
      structure and a large uncalcified bone matrix. These findings implied the early
      phase of osteoporosis induced by heparin use. The combination of vitamins E and C
      given to the experimental rabbits partially prevented this bone tissue
      destruction. When sodium selenite was given together with vitamins E and C to the
      osteoporosis model rabbits, the long bone tissue had almost the same structure as
      in normal rabbits, for example the development of numerous bone trabeculae. Our
      results suggest that a combination of sodium selenite with vitamins E and C was
      more effective than combinations of single vitamins to prevent structural
      alterations in these model bones.

PMID- 14677022
TI  - Alkaptonuric ochronosis: a case with multiple joint replacement arthroplasties.
AB  - Alkaptonuria is an extremely rare hereditary disorder of metabolism which may
      affect various systems. Degeneration of the articular surfaces in major joints
      leads to complications, which may further necessitate joint replacements. In this
      report, a case of advanced alkaptonuria with multiple joint replacements is
      presented and musculoskeletal system involvement in this disorder is reviewed.

PMID- 14677023
TI  - The burden of amyloidosis on the gastrointestinal tract of an ankylosing
      spondylitis patient.
AB  - We present a 26-year-old man with edema, ascites and bloody diarrhea that later
      proved to be due to gastrointestinal and renal amyloidosis. Interestingly, he was
      also diagnosed as having ankylosing spondylitis,-possibly after a delay of 12
      years. The obscure diagnosis and challenging treatment of secondary amyloidosis
      are further discussed.

PMID- 14677025
TI  - Acute acalculous cholecystitis induced by mesenteric inflammatory veno-occlusive
      disease (MIVOD) in systemic lupus erythematosus.
AB  - A 43-year-old woman with systemic lupus erythematosus (SLE) was treated for lupus
      pleurisy. During the course of her illness, she abruptly suffered severe right
      hypochondriac pain and high-grade fever. Abdominal ultrasonography revealed a
      thickening of the gallbladder wall without cholelithiasis, and she was diagnosed
      with acute acalculous cholecystitis (AAC). Laparoscopic cholecystostomy was
      performed. Pathological examination revealed lymphocytic venulitis without
      arteritis. Antiphospholipid antibodies were not demonstrated during the course of
      illness. From these findings, the cause of AAC was revealed as a mesenteric
      inflammatory veno-occlusive disease (MIVOD), which is a novel venopathy mainly
      affecting the mesenteric vein and/or its branches, causing serious ischemic
      complications. MIVOD should be considered as a possible cause of AAC.

PMID- 14677024
TI  - Spondylodiscitis as the first manifestation of Whipple's disease -a removal
      worker with chronic low back pain.
AB  - Whipple's disease is a rare systemic infectious disease caused by the
      actinobacterium Tropheryma whipplei. Spondylodiscitis is an extremely rare
      manifestation of the infection and has previously been described in only three
      case reports. We present a 55-year-old man with persistent lumbago and signs of
      systemic illness, but without any gastrointestinal symptoms or arthralgia. The
      signal response in the lumbar spine in magnetic resonance tomography, both native
      and after intravenous gadolinium administration, was compatible with
      spondylodiscitis at the L4/L5 level. Culture of a specimen obtained by
      radiographically guided disc puncture and repeated blood cultures remained
      sterile. Tropheryma whipplei was detected by PCR amplification in material
      obtained from the disc specimen, from a biopsy of the terminal ileum and from the
      stool. The histology of duodenum, terminal ileum, colon and disc material was
      normal and, in particular, showed no PAS-positive inclusions in macrophages. Long
      term antibiotic treatment with sulphamethoxazole and trimethoprim was successful,
      with marked improvement of the low back pain and normalisation of the systemic
      inflammatory signs. The possibility of Whipple's disease must be suspected in the
      case of a 'culture-negative' spondylodiscitis even if there are no
      gastrointestinal symptoms and no arthralgia present.

PMID- 14677026
TI  - Diabetic muscular infarction: emphasis on pathogenesis.
AB  - Diabetic muscular infarction is a rare complication of diabetes. It usually
      occurs in those with target organ involvement of diabetes, generally affecting
      one or a group of muscles of the thigh, and can recur. The pathogenesis of the
      disease is still not clear. Here we report an unusual case of extensive muscle
      involvement of both thighs and calves, with special emphasis on pathogenesis.

PMID- 14677027
TI  - Visceral leishmaniasis resembling systemic lupus erythematosus.
AB  - We describe three cases with visceral leishmaniasis (VL) associated with
      autoimmune manifestations. The patients presented with anemia, leukopenia,
      thrombocytopenia, renal involvement and low complement levels. Autoimmune
      features were present (antinuclear and anticardiolipin antibodies, VDRL, RF,
      positive direct Coombs' test), which subsided after therapy. Leishmaniasis should
      be taken into consideration in the differential diagnosis of autoimmune
      disorders.

PMID- 14677028
TI  - Emery-Dreifuss muscular dystrophy in the evaluation of decreased spinal mobility
      and joint contractures.
AB  - In this report we present three patients who had complaints primarily related to
      joints and flexibility. Two had no specific diagnosis and one was thought to have
      ankylosing spondylitis. Extensive evaluation revealed Emery-Dreifuss muscular
      dystrophy (EDMD) in all. EDMD is a muscular dystrophy where joint contractures
      and spinal limitation occur before any overt muscle weakness, and the syndrome
      may be combined with serious cardiac pathology. We wish to call the attention of
      professionals involved in rheumatology and physical medicine to the existence of
      this syndrome, which may only present with joint contractures and spinal
      limitation but which may end with fatal cardiac problems if not diagnosed in
      time.

PMID- 14677029
TI  - Kawasaki disease in an infant following immunisation with hepatitis B vaccine.
AB  - The known association between hepatitis B and vasculitis has been reported in
      rare cases in adults after hepatitis B vaccination. We here describe a 35-day-old
      infant who developed Kawasaki disease 1 day after receiving his second dose of
      hepatitis B vaccine. Although extremely rare, this possible side effect should be
      noted and further investigated.

PMID- 14677030
TI  - Aggressive and atypical manifestations of Erdheim-Chester disease.
AB  - Erdheim-Chester disease (ECD) is a disseminated non-Langerhans' cell
      histiocytosis with multisystem involvement, including characteristic sclerotic
      musculoskeletal lesions. We present the case of a 27-year-old woman with a
      fulminant course and atypical involvement by ECD manifesting as extensive
      cerebrovascular disease and lytic musculoskeletal lesions. This case represents
      an unusual and aggressive presentation of ECD owing to the patient's young age,
      the severity of the cerebrovascular involvement and the lytic osseous lesions.

PMID- 14677031
TI  - Clinical and histological coexistence of inflammatory pseudotumour of the lymph
      nodes and rheumatoid arthritis.
AB  - Inflammatory pseudotumour (IPT) of the lymph nodes is an uncommon, self-limiting,
      non-neoplastic proliferation of spindle cells, associated with a polymorphous
      inflammatory cell infiltrate embedded in a collagen-rich stroma and a variable
      degree of fibrosis, arising in the nodal parenchyma. Its clinical picture is
      characterised by site-specific signs and the presence, in most cases, of
      constitutional symptoms. The pathogenesis of IPT is unknown, but it has been
      interpreted as an aberrant reactive condition of the nodal connective framework,
      possibly related to viral infections or chronic inflammatory conditions. Its
      prognosis is usually favourable. We here report the simultaneous onset of
      seronegative rheumatoid arthritis (RA) and nodal IPT in a 31-year-old woman.
      Notably, in the nodal biopsy the coexistence of rheumatoid nodules, as well as
      histological and immunohistochemical features of IPT, was observed. To our
      knowledge, such an association has not been previously reported and the
      hypothesis that IPT could represent an unusual epiphenomenon of an RA-related
      chronic inflammatory response is suggested.

PMID- 14677032
TI  - Pseudotumour orbitae as the initial manifestation in Wegener's granulomatosis in
      a 7-year-old girl.
AB  - Wegener's granulomatosis (WG) is a systemic granulomatous vasculitis that
      typically affects the upper airways, lungs and kidneys. This form of vasculitis
      is extremely rare in children, the most common form of paediatric systemic
      vasculitis being Henoch-Schonlein purpura (HSP). Children with systemic
      vasculitis look ill and have multiple constitutional complaints, often with
      prolonged fever. As in adults, WG in children is a multisystem disease. There are
      no precise statistical data concerning ocular involvement in Wegener's
      granulomatosis in children. Ocular disease occurs in 50%-60% adult patients with
      WG and may be an extension of the sinus inflammation or an orbital pseudotumour
      independent of the sinus disease (15%-50%); sometimes it presents as an ocular
      myositis. The most common presenting sign of orbital disease is ptosis and
      anterior displacement of the eye, pain, blurred vision, eyelid swelling and
      reduction of eye motility. Here we present the case of a 7-year-old girl with WG
      whose initial manifestation was pseudotumour orbitae. This patient was negative
      for an initial c-ANCA test. Biopsy specimens obtained from the lacrimal gland and
      kidney demonstrated granulomatous vasculitis. Treatment with glucocorticoids and
      cyclophosphamide led to complete, long-lasting remission.

PMID- 14677033
TI  - Rheumatoid meningitis: an autopsy report and review of the literature.
AB  - We report the clinical and autopsy findings of a 71-year-old Japanese woman with
      rheumatoid meningitis. This patient developed subacute meningitis during an
      inactive stage of rheumatoid arthritis (RA), and despite intensive examinations
      no causative agents or underlying disease could be identified except for RA.
      Based on persistent hypocomplementaemia and increased serum levels of immune
      complexes she was suspected of having vasculitis, and was treated with
      intravenous methylprednisolone (1000 mg/day for 3 days) followed by oral
      prednisolone. Soon after beginning treatment with corticosteroid her symptoms
      improved, in parallel with a decrease in cell counts and interleukin-6 in the
      cerebrospinal fluid. During tapering of oral prednisolone she died of a
      subarachnoid haemorrhage which was ascribed to a relapse of the meningitis.
      Autopsy demonstrated infiltration of mononuclear cells, including plasma cells,
      in the leptomeninges, mainly around small vessels, leading to a definite
      diagnosis of rheumatoid meningitis. When RA patients manifest intractable
      meningitis with a subacute course, this disease is important as a possible
      diagnosis even if the arthritis is inactive, and intensive treatment, including
      corticosteroid and immunosuppressants, should be positively considered as a
      therapeutic option as soon as possible because of the poor prognosis.

PMID- 14677034
TI  - An uncommon cause of fever in the elderly: late-onset systemic lupus
      erythematosus.
AB  - Infections, tumors and multisystem disease are common causes of fever of unknown
      origin (FUO) in the elderly. Late-onset systemic lupus erythematosus (LO-SLE) is
      a very rare cause of FUO in elderly patients. Serositis and musculoskeletal
      manifestations are common, but fever as an initial manifestation in LO-SLE is
      rare. We present two patients with LO-SLE who manifested fever as an initial
      symptom. Fever was the only symptom for 2 months in the first case and for 3
      months in the second. In conclusion, in geriatric patients who have fever, LO-SLE
      should be considered in the differential diagnosis.

PMID- 14677035
TI  - Systemic juvenile idiopathic arthritis mimics multicentric Castleman's disease.
AB  - An 11-year-old girl presented with fever and a large cervical lymphadenopathy.
      Indicators of inflammation were remarkable: she had extremely high levels of
      serum interleukin-6 (IL-6) (398 pg/ml) in addition to hypergammaglobulinemia and
      hypoalbuminemia. Computed tomography (CT) revealed swollen systemic lymph nodes.
      Two weeks after the onset of symptoms she developed polyarthralgia. Biopsy of the
      cervical lymph node revealed massive infiltration of plasma cells without hyaline
      vascular changes. She was diagnosed with systemic juvenile idiopathic arthritis
      (JIA). The patient's symptoms and hypercytokinemia disappeared soon after
      corticosteroid treatment was started. This case demonstrates that overproduction
      of IL-6 is common to systemic JIA and multicentric Castleman's disease.

PMID- 14677036
TI  - Acute myocarditis associated with adenoviral infection in a patient with
      scleroderma.
AB  - We describe a 40-year-old man with limited scleroderma who presented with acute
      heart failure following a flu-like illness. He was known to have incomplete left
      anterior bundle branch block, initial isolated pulmonary hypertension with
      enlarged right atrium, and no pulmonary fibrosis. He received therapy for acute
      heart failure and was transferred to a scleroderma centre for specific treatment
      of scleroderma cardiomyopathy. Investigations showed raised inflammatory markers
      and diffuse hyperechogenic thickening of the myocardium on echocardiography.
      Contrast-enhanced (Gd-DOTA) cardiovascular magnetic resonance imaging (CV-MRI)
      showed multiple areas of non-homogeneous delayed hyperenhancement in the left
      ventricle, suggestive of myocarditis. Antiadenovirus IgM antibodies were detected
      with a titer consistent with recent infection. Six weeks later a repeat Gd-DOTA
      CV-MRI showed an almost complete resolution of the areas of hyperenhancement and
      there was a significant reduction in the adenovirus antibody titer with
      serological conversion to IgG. To our knowledge this is the first report of viral
      myocarditis in scleroderma. Infections are important causes of morbidity and
      mortality in this disease and should always be included in the differential
      diagnosis of cardiac symptoms. We propose that contrast-enhanced CV-MRI is
      valuable in a non-invasive diagnosis of heart disease in patients with
      scleroderma.

PMID- 14677037
TI  - Churg-Strauss syndrome (CSS) in a patient receiving pranlukast.
AB  - Pranlukast is a cysteinyl leukotriene receptor I antagonist (LTRAs) approved for
      treatment of asthma in Japan since 1995. Compared to other LTRAs, such as
      zafilukast and montelukast, only few cases with Churg-Strauss syndrome (CSS) have
      been reported in association with treatment with pranlukast. We describe a 17
      year-old Japanese male patient who developed CSS with a 13 month history of mild
      asthma receiving pranlukast for 11 months without systemic and/or inhaled
      corticosteroid administration prior to development of CSS. From the aspect of
      temporal relationship between treatment with pranlukast and development of CSS, a
      direct induction of CSS by pranlukast is suggested in our case.

PMID- 14677038
TI  - Analysis of risk factors and comorbid diseases in the development of thrombosis
      in patients with anticardiolipin antibodies: comment on the article by Sairam et
      al.

PMID- 14677039
TI  - High prevalence of thyroid autoantibodies in systemic sclerosis and rheumatoid
      arthritis but not in the antiphospholipid syndrome.

PMID- 14677040
TI  - Usefulness of technetium-99m tetrofosmin SPECT to detect abnormal myocardial
      perfusion in systemic lupus erythematosus or systemic sclerosis patients.

PMID- 14677041
TI  - Neurofibromatosis and systemic lupus erythematosus. A matter of coincidence?

PMID- 14677042
TI  - Pulmonary aneurysms in microscopic polyangiitis.

PMID- 14677043
TI  - Ciprofloxacin and Achilles' tendon rupture: a causal relationship.

PMID- 14677044
TI  - An ankylosing spondylitis patient 'with no joints'.

PMID- 14677045
TI  - Coexisting seronegative rheumatoid arthritis and ankylosing spondylitis.

PMID- 14677046
TI  - Elevated serum levels of manganese superoxide dismutase in patients with
      eosinophilic fasciitis.

PMID- 14677047
TI  - Symmetrical pitting edema resembling RS3PE in gout.

PMID- 14677048
TI  - Colour duplex ultrasonography in the management of giant cell arteritis.

PMID- 14677049
TI  - Combined effects of PPARgamma2 P12A and PPARalpha L162V polymorphisms on glucose
      and insulin homeostasis: the Quebec Family Study.
AB  - Peroxisome proliferator-activated receptors gamma2 and alpha are nuclear factors
      known to be important regulators of lipid and glucose metabolism. Two
      polymorphisms, namely PPARgamma2 P12A and PPARalpha L162V, were investigated for
      their individual and interaction effects on glucose and insulin homeostasis.
      Genotypes were determined in 663 nondiabetic adults participating in the Quebec
      Family Study and who underwent an oral glucose tolerance test (OGTT). The insulin
      and C-peptide areas under the curve (AUC) following the OGTT were higher in
      subjects carrying the PPARalpha V162 allele compared to homozygous for the L162
      allele. When subjects were grouped according to both polymorphisms, higher levels
      of insulin and C-peptide during the OGTT were observed for those carrying the
      PPARalpha V162 allele except when they carry at the same time the PPARgamma2 A12
      allele. Thus, the PPARgamma2 A12 allele seems protective against the deleterious
      effect of the PPARalpha V162 allele. Furthermore, a significant gene-gene
      interaction was observed for the acute (0-30 min) (p<0.001) and the total
      (p=0.05) C-peptide AUC following the OGTT. These results provide evidence of a
      gene-gene interaction in the regulation of plasma glucose-insulin homeostasis,
      and emphasize that these interactions need to be taken into account when
      dissecting the genetic etiology of complex disorders.

PMID- 14677050
TI  - Structures and stability of N13+ and N13- clusters.
AB  - The structures and stabilities of eleven N13+ and N13- isomers have been
      investigated with second-order Moller-Plesset (MP2) and density functional theory
      (DFT) methods. Five N13+ isomers and six N13- isomers are all reasonable local
      minima on their potential energy hypersurfaces. The most stable N13+ cation is
      structure C-2 with C2v symmetry, which contains a pentazole ring and two N4 open
      chains. It is different from those of the N7+ and N9+ clusters, but similar to
      the N11+ cluster. Meanwhile, the most stable N13- structure A-2 is composed of a
      pentazole ring and a six-membered ring connected by two nitrogen atoms. It is not
      only different from those of the N7- and N9- clusters, but also from the N11-
      cluster. The decomposition pathways of structures C-2 and A-2 were investigated
      at the B3LYP/(aug)-cc-pVDZ level. From the barrier heights of the structures C-2
      and A-2 decomposition processes, it is suggested that C-2 is difficult to observe
      experimentally and A-2 may be observed as a short-lived species.

PMID- 14677051
TI  - Cytotoxicity and oxidative stress caused by dental adhesive systems cured with
      halogen and LED lights.
AB  - The aim of the present study was to investigate the cytotoxicity of two "one
      bottle" adhesive systems after polymerization with a conventional halogen or a
      light emitting diode (LED) lamp. We hypothesized that different polymerization
      sources might enhance the intracellular production of reactive oxygen species
      (ROS), leading to reduced cell survival. Two "one bottle" adhesive systems
      (Optibond Solo and Scotchbond One) were cured with a commercial halogen (Optilux
      500) and an LED source (Elipar Freelight, 3 M). The specimens were extracted for
      24 h in complete cell culture medium or in phosphate-buffered saline (PBS).
      Endothelial cells (ECV 304) were exposed to the extracts for 24 h and survival
      rates were evaluated by the MTT assay. Then, ROS generation was monitored by the
      oxidation-sensitive fluorescent probe 2'7'-dichlorofluorescin diacetate (DCFH
      DA). Extracts from all materials except for Optibond Solo polymerized with the
      halogen lamp were rated significantly cytotoxic. Scotchbond One cured with LED
      was the most toxic material, which reduced cell survival to about 23% compared
      with control cultures. Significantly higher amounts of ROS were produced in cell
      cultures treated with adhesives polymerized with the LED lamp compared with the
      materials cured with the commercial halogen light source. We demonstrated that
      the production of intracellular ROS by extracts of the adhesive systems depended
      on the light sources used for curing of the materials. These results suggested a
      possible link between ROS production and cytotoxic activity.

PMID- 14677053
TI  - Reversible posterior leukoencephalopathy in a patient with Wegener
      granulomatosis.
AB  - A 14-year-old girl with rapidly progressive glomerulonephritis was transferred to
      our hospital because of acute renal failure. A diagnosis of Wegener
      granulomatosis was made according to the symptom triad of a renal biopsy
      demonstrating crescentic glomerulonephritis, severe sinusitis, and serological
      findings of raised proteinase 3 anti-neutrophil cytoplasmic antibody level. In
      spite of combination therapy with methylprednisolone, cyclophosphamide, and
      plasma exchange, her renal function gradually deteriorated. Thereafter, she
      suffered a severe headache and generalized seizures. Brain computed tomography
      (CT) scan revealed bilateral low-density areas in the parieto-occipital lobes.
      Magnetic resonance imaging (MRI) disclosed a high-intensity area on T2-weighted
      images and a low-signal intensity area on T1-weighted images in the same lesion.
      Follow-up brain CT scan 3 weeks and MRI 2 months after the first studies showed
      complete resolution of the abnormal lesions, which indicated reversible posterior
      leukoencephalopathy syndrome. In addition to renal failure, hypertension, and
      cyclophoshamide, the primary disease may have played a role in the development of
      this uncommon syndrome in our patient.

PMID- 14677054
TI  - Renal tubular dysgenesis and neonatal hemochromatosis without pulmonary
      hypoplasia.
AB  - Renal tubular dysgenesis is a rare disorder of differentiation of the fetal
      kidney. The condition has previously been reported as a postmortem diagnosis in
      infants who have had oligohydramnios commencing after 20 weeks gestation and have
      died of renal or respiratory failure shortly after birth with a clinical
      description of Potter sequence. The absence of clinically significant pulmonary
      hypoplasia in our case serves to emphasize that renal tubular dysgenesis, fetal
      anuria and long-standing oligohydramnios can occur without pulmonary
      insufficiency. The coexistence of renal tubular dysgenesis with neonatal
      hemochromatosis has been previously described in four published cases. The link
      between these two rare conditions is clinically important if dialysis or liver
      transplantation is considered in infants with hepatic and renal failure.
      Antemortem diagnosis by renal biopsy in our case enabled parental counseling and
      avoided the inappropriate use of peritoneal dialysis.

PMID- 14677055
TI  - Increased expression of mast cells in reflux nephropathy.
AB  - End-stage renal disease is characterized by interstitial infiltrate of
      inflammatory cells in association with tubular atrophy and interstitial fibrosis.
      Mast cells (MCs) secrete a large number of fibrogenic factors and have been
      implicated in chronic inflammatory processes with fibrous tissue deposition. The
      aim of this study was to investigate the distribution of MCs in kidneys with
      reflux nephropathy (RN) and to determine the relationship between MCs and the
      interstitial fibrotic process in RN. Kidney specimens from 12 patients (aged 2-13
      years) with severe RN secondary to primary high-grade vesicoureteral reflux,
      obtained at the time of nephrectomy, and 5 controls were examined. Sections were
      investigated histochemically by acid toluidine blue (TB) and
      immunohistochemically with antibodies for anti MC-tryptase, MC-chymase, c- kit
      (CD117), and fibronectin. Double staining for fibronectin and MC-tryptase was
      performed and examined using confocal scanning microscopy. TB histochemistry
      showed a marked increase of MCs in RN specimens compared with controls. MC
      tryptase, chymase, and c- kit immunopositive MC infiltration was significantly
      higher in RN samples (14.2+/-9.6) than controls (1.3+/-0.8), ( P<0.05). In all
      the sections there were more MC-tryptase-positive cells than MC-chymase-positive
      MCs. Double staining showed increased immunoreactivity of MCs and fibrosis in the
      renal interstitium of kidneys with RN. The number of infiltrating tryptase
      positive MCs was correlated with the degree of interstitial renal scarring. This
      study demonstrates for the first time the increased expression of MCs in RN,
      suggesting that MCs may be involved in the development of scarring in RN.

PMID- 14677056
TI  - Growth plate height of uremic rats is influenced by severity and duration of
      renal failure.
AB  - To understand the changes induced by uremia in the epiphyseal growth plate, two
      studies were performed in young rats. In study 1, the morphological features of
      the tibial growth cartilage of stunted rats with different degrees of reduction
      of renal function were analyzed 2 weeks after nephrectomy and compared with
      control rats. There was a negative ( r=-0.549, P<0.05) correlation between serum
      urea nitrogen (SUN) concentrations and longitudinal growth rate. The heights
      (mean+/-SEM) of growth cartilage (564+/-32 vs. 366+/-9 microm) and its
      hypertrophic zone (321+/-25 vs. 157+/-6 microm) were greater ( P<0.05) in uremic
      than control rats and were highly and positively correlated ( r=0.604, P<0.03 and
      r=0.706, P<0.01) with SUN levels. In study 2, the time course of growth plate
      alterations was investigated in uremic rats sacrificed 1 (NX-1), 2 (NX-2), and 4
      weeks (NX-4) after nephrectomy compared with their corresponding control animals
      (C-1, C-2, C-4). Growth cartilage and hypertrophic zone heights were greater in
      NX-2 (533+/-60 and 264+/-32 microm) than in C-2 (345+/-10 and 131+/-11 microm),
      with no significant differences in the other groups. This report shows that
      enlargement of the growth plate and its hypertrophic stratum is greatly, although
      not exclusively, influenced by the severity and duration of renal insufficiency.

PMID- 14677057
TI  - Henoch-Schonlein purpura nephritis associated with Epstein-Barr virus infection
      in twins.

PMID- 14677058
TI  - Selection and reversal of Plasmodium berghei resistance in the mouse model
      following repeated high doses of artemether.
AB  - Artemether, a derivative of artemisinin, is effectively used for the treatment of
      malaria without any clinically relevant resistance to date. Artemether has also
      been developed as an antischistosomal agent, exhibiting highest activity against
      immature parasites. Here, we employ a rodent model and investigate whether the
      proposed artemether treatment schedule to prevent schistosome-attributable
      morbidity might select for Plasmodium berghei resistance. Mice infected with an
      ANKA strain of P. berghei were treated with artemether at either 47 mg/kg or 300
      mg/kg. Once every 7-10 days, parasitized erythrocytes were passed to the next
      group of mice, receiving the same doses of artemether, for 50 passages.
      Resistance development was slow but increased considerably over the final ten
      passages. At the higher dose of artemether, the indices of resistance were 4.8
      and 8.8 after 40 and 50 passages, respectively. Importantly, resistance was
      unstable, since sensitivity reverted to near-normal after five passages without
      drug pressure. A moderate index of P. berghei resistance and no apparent
      reversibility was found in comparative experiments employing pyronaridine. In
      conclusion, the pace of resistance development in P. berghei to repeated high
      doses of artemether is slow and reversible.

PMID- 14677059
TI  - Liposome-complexed adenoviral gene transfer in cancer cells expressing various
      levels of coxsackievirus and adenovirus receptor.
AB  - PURPOSE: Loss of coxsackievirus and adenovirus receptor (CAR) is frequently
      observed in malignant cancer, hampering adenoviral gene therapy approaches.
      Complexing adenovirus with cationic liposomes can increase adenoviral transgene
      expression, particularly in cells with CAR-deficiency. We investigated whether
      other factors such as lipid composition might be involved in determining the
      efficiency of liposome-complexed adenoviral gene transfer in cancer cells.
      MATERIAL AND METHODS: Human cancer cell lines with different expression levels of
      CAR were infected with a GFP transgene. The efficiency of transgene expression
      was assessed by determining GFP expression using FACS analysis. RESULTS: The
      efficiency of liposome-complexed adenoviral gene transfer was dependent on the
      lipid composition constituting liposomes. Polyethylene glycol (PEG)-containing
      liposomes were most effective in increasing liposome-complexed adenoviral gene
      transfer. In CAR-deficient cells, use of PEG-containing liposomes enhanced
      adenoviral gene transfer, whereas in CAR-expressing cells enhancement varied
      depending on cell type. In some CAR-expressing cells, the effect of liposome
      complexing was even comparable to that in CAR-deficient cells. Increased
      adenoviral transgene expression following complexing with PEG-containing
      liposomes correlated with liposome uptake in cancer cells. CONCLUSIONS: Liposome
      complexed adenoviral gene transfer appears to depend on lipid composition and the
      level of liposome uptake by cancer cells, in addition to CAR levels. Our study
      suggest that these multiple factors should be considered in designing liposome
      complexed adenoviral vectors to improve outcomes of current adenoviral cancer
      gene therapies.

PMID- 14677060
TI  - A novel gain-of-function mutation (F821L) in the transmembrane domain of calcium
      sensing receptor is a cause of severe sporadic hypoparathyroidism.
AB  - Gain-of-function mutations of the extracellular calcium (Ca(2+)e)-sensing
      receptor (CaR) have been identified in patients with familial and sporadic
      hypercalciuric hypocalcaemia. We describe a patient with sporadic severe
      hypercalciuric hypocalcaemia with undetectable or very low levels of serum
      parathyroid hormone, carrying a de novo heterozygous missense mutation ( F821L),
      localized in the sixth transmembrane domain of CaR. Analysis of in vitro
      functional properties of the mutant receptor to measure Ca(2+)e-evoked changes in
      intracellular Ca(2+) revealed a leftward shift in the concentration-response
      curve for the mutant compared to wild-type receptor. CONCLUSION: the
      F821Lmutation is therefore a novel gain-of-function mutation which can cause
      severe hypoparathyroidism. Thiazide diuretics lowered urinary calcium excretion
      of the patient treated with calcium supplementation and 1alpha-hydroxyvitamin
      D(3.)

PMID- 14677061
TI  - Pediatric non-neuronopathic Gaucher disease: presentation, diagnosis and
      assessment. Consensus statements.
AB  - Gaucher disease is caused by defective activity of glucocerebrosidase. The
      resulting accumulation of glucocerebroside in the lysosomes of visceral
      macrophages in various tissue and organ compartments leads to multiple
      manifestations, including hepatosplenomegaly, anemia, thrombocytopenia, growth
      retardation and skeletal disease. The most prevalent form of Gaucher disease is
      the non-neuronopathic (type 1) variant, which lacks primary involvement of the
      central nervous system. Traditionally, this has been referred to as the 'adult
      type'; however, 66% of individuals with symptomatic non-neuronopathic Gaucher
      disease manifest in childhood. Onset in childhood is usually predictive of a
      severe, rapidly progressive phenotype and children with non-neuronopathic Gaucher
      disease are at high risk for morbid complications. Enzyme therapy with
      recombinant human glucocerebrosidase in childhood can restore health in
      reversible manifestations and prevent the development of irreversible symptoms. A
      heightened focus on pediatric Gaucher disease is therefore needed. Although some
      correlation has been found between genotype and phenotype, mutation analysis is
      of limited value in disease prognosis. Management of pediatric Gaucher disease
      should be underpinned by a thorough assessment of the phenotype at baseline with
      regular monitoring thereafter. Excluding neuronopathic disease is recommended as
      the first step. Subsequently, baseline evaluation should focus on staging of
      different storage tissues, particularly the bone the involvement of which results
      in the greatest long-term morbidity. These organ assessments are recommended
      because bone disease severity may not correlate with disease severity in other
      organs and vice versa. In addition, different organs may respond differently to
      therapy. Initial assessment of each organ system can enable setting of realistic
      and individualized goals. CONCLUSION: A thorough approach to baseline assessment
      will improve the understanding of childhood Gaucher disease, optimizing
      management to minimize impairment of growth and development and prevent
      irreversible symptoms.

PMID- 14677063
TI  - Prolonged survival in alveolar capillary dysplasia syndrome.

PMID- 14677062
TI  - Paediatric non-neuronopathic Gaucher disease: recommendations for treatment and
      monitoring.
AB  - In individuals with non-neuronopathic Gaucher disease, childhood manifestations
      are usually predictive of a more severe phenotype. Although children with Gaucher
      disease are at risk of irreversible disease complications, early intervention
      with an optimal dose of enzyme therapy can prevent the development of
      complications and ensure adequate, potentially normal, development through
      childhood and adolescence. Very few, if any, children diagnosed by signs and
      symptoms should go untreated. Evidence suggests that disease severity, disease
      progression and treatment response in different organs where glucocerebroside
      accumulates are often non-uniform in affected individuals. Therefore, serial
      monitoring of the affected compartments is important. This should include a
      thorough physical examination at 6- to 12-monthly intervals. Neurological
      assessment should be performed to rule out neurological involvement and should be
      undertaken periodically thereafter in children who are considered to have risk
      factors for developing neuronopathic disease. Haematological and biochemical
      markers, such as haemoglobin, platelet counts and chitotriosidase levels, should
      be assessed every 3 months initially, but when clinical goals have been met
      through treatment with enzyme therapy, the frequency can be reduced to every 12
      to 24 months. Careful monitoring of bone disease is vitally important, as the
      resulting sequelae are associated with the greatest level of morbidity. By
      combining various imaging modalities, the skeletal complications of non
      neuronopathic Gaucher disease can be effectively monitored so that irreversible
      skeletal pathology is avoided and pain due to bone involvement is diminished or
      eliminated. Monitoring must include regular psychosocial, functional status and
      quality-of-life evaluation, as well as consistent assessment of therapeutic goal
      attainment and necessary dosage adjustments based on the patient's progress.
      CONCLUSION: Through comprehensive and serial monitoring, ultimately, a
      therapeutic dose of enzyme therapy that achieves sustained benefits can be found
      for each child with non-neuronpathic Gaucher disease.

PMID- 14677064
TI  - Early diagnosis of inherited metabolic diseases: towards improving outcome.
      Proceedings of an international symposium. November 21-23, 2001. Fulda, Germany.

PMID- 14677065
TI  - Rare KIT (CD117) expression in multiple myeloma abrogates the usefulness of
      imatinib mesylate treatment.
AB  - BACKGROUND: Imatinib mesylate blocks the tyrosine kinase activity of KIT (CD117)
      and is an effective treatment for gastrointestinal stromal tumors. In multiple
      myeloma, KIT expression has been detected by flow cytometry in about 33% of
      specimens, but no previous immunohistochemical assessment has yet been made of
      the expression pattern of KIT. MATERIALS AND METHODS: We performed
      immunohistochemical analyses of 100 patients, including 72 with multiple myeloma
      (MM), 8 with lymphoplasmacytic lymphoma (LPL), 10 with monoclonal gammopathy of
      undetermined significance (MGUS) and 10 with reactive plasmocytosis. One KIT
      positive MM was sequenced using polymerase chain reaction analysis. RESULTS: In
      MM, only 2 cases (2.8%) were KIT positive. The great majority of the cases (97,
      2%) did not express the KIT receptor tyrosine kinase. No mutation of the c-kit
      gene was detected. CONCLUSIONS: KIT expression is a rare event in MM and not
      detectable in MGUS and LPL. Therefore, treatment with imatinib is unlikely to be
      effective in these patients.

PMID- 14677067
TI  - Voltage-gated Na+ channels confer invasive properties on human prostate cancer
      cells.
AB  - Prostate cancer is the second leading cause of cancer deaths in American males,
      resulting in an estimated 37,000 deaths annually, typically the result of
      metastatic disease. A consequence of the unsuccessful androgen ablation therapy
      used initially to treat metastatic disease is the emergence of androgen
      insensitive prostate cancer, for which there is currently no prescribed therapy.
      Here, three related human prostate cancer cell lines that serve as a model for
      this dominant form of prostate cancer metastasis were studied to determine the
      correlation between voltage-gated sodium channel expression/function and prostate
      cancer metastatic (invasive) potential: the non-metastatic, androgen-dependent
      LNCaP LC cell line and two increasingly tumorogenic, androgen-independent
      daughter cell lines, C4 and C4-2. Fluorometric in vitro invasion assays indicated
      that C4 and C4-2 cells are more invasive than LC cells. Immunoblot analysis
      showed that voltage-gated sodium channel expression increases with the invasive
      potential of the cell line, and this increased invasive potential can be blocked
      by treatment with the specific voltage-gated sodium channel inhibitor,
      tetrodotoxin (TTX). These data indicate that increased voltage-gated sodium
      channel expression and function are necessary for the increased invasive
      potential of these human prostate cancer cells. When the human adult skeletal
      muscle sodium channel Na(v1.4) was expressed transiently in each cell line, there
      was a highly significant increase in the numbers of invading LC, C4, and C4-2
      cells. This increased invasive potential was reduced to control levels by
      treatment with TTX. These data are the first to indicate that the expression of
      voltage-gated sodium channels alone is sufficient to increase the invasive
      potential of non-metastatic (LC cells) as well as more aggressive cells (i.e., C4
      and C4-2 cells). Together, the data suggest that increased voltage-gated sodium
      channel expression alone is necessary and sufficient to increase the invasive
      potential of a set of human prostate cancer cell lines that serve as a model for
      prostate cancer metastasis.

PMID- 14677066
TI  - A novel cell line and xenograft model of ampulla of Vater adenocarcinoma.
AB  - Ampulla of Vater cancers (AVC) are of clinical relevance, as they represent more
      than one-third of patients undergoing surgery for pancreaticoduodenal
      malignancies and have a better prognosis than periampullary cancers of
      pancreaticobiliary origin. The availability of cellular models is crucial to
      perform cell biology and pharmacological studies and clarify the relationship
      between AVC and pancreatic and biliary cancers. Numerous cell lines are available
      for pancreatic and biliary adenocarcinomas, while only two have been reported
      recently for AVC. These were derived from a poor and a well-differentiated AVC,
      and both had wild-type K- ras and mutated p53. We report the establishment of a
      novel AVC cell line (AVC1) derived from a moderately differentiated cancer,
      having a mutated K- ras, wild-type p53, and methylated p16. Thus, our cell line
      adds to the spectrum of available in vitro models representative of the different
      morphological and molecular presentations of primary AVC. We further
      characterized AVC1 for the expression of relevant cell surface molecules and
      sensitivity to chemotherapeutic agents of common clinical use. It expresses MHC-I
      and CD95/Fas, while HLA-DR, CD40, CD80, CD86, MUC-1, MUC-2, and ICAM-1/CD54 are
      absent. It has a low to moderate sensitivity to both 5-FU and gemcitabine, at
      variance with much higher sensitivity displayed by two pancreatic ductal
      carcinoma cell lines. Lastly, AVC1 can be readily xenografted in immunodeficient
      mice, making it a suitable model for pre-clinical studies.

PMID- 14677068
TI  - The slow component of VO(2) kinetics in very heavy and fatiguing square-wave
      exercise.
AB  - We hypothesized that oxygen consumption ( VO(2)) rises incrementally in very
      heavy and fatiguing exercise where the slow component gain increases with higher
      work rates. Eight trained males completed a graded exercise test and bouts of
      square-wave cycle ergometry at 40% and 60% of the difference between the
      estimated lactate threshold (LT) and VO(2peak) (designated 40%D and 60%D).
      Exhaled gases were collected and analyzed every breath using models that allowed
      for a linear slow component or a slow component with one or more exponential
      increments. All subjects were able to complete 30 min at 40%D but not at 60%D.
      The slow component was generally best fit with two increments at 40%D and two or
      three increments at 60%D. In further (<Emphasis Type="Italic">, our results
      question the reliability of determining parameters of multiple slow component
      increments when repeated bouts are averaged together. This study demonstrates
      that VO(2) can continue to rise incrementally beyond the onset of the slow
      component in very heavy and fatiguing exercise. These results support the concept
      of a recurring mechanism underlying the slow component of VO(2) kinetics during
      square-wave exercise and suggest that the dynamics (time of onset, rate of
      development, magnitude) of this mechanism may vary from day to day.

PMID- 14677069
TI  - The amplitude of the slow component of oxygen uptake is related to muscle
      contractile properties.
AB  - During constant-load exercise above the lactate threshold, oxygen-uptake kinetics
      deviate from the pattern seen below the threshold, with an additional, delayed
      component superimposed on the monoexponential pattern. It was hypothesised that
      this slow component is due to the progressive recruitment of type II muscle
      fibres. Oxygen uptake was measured for six male power athletes (group P) and six
      male endurance athletes (group E) during constant-load knee extension exercise
      tests in order to determine slow component amplitude. In addition, an electrical
      stimulation protocol was employed in order to assess the functional contractile
      profile and fatiguability of the knee extensors. The amplitude of the slow
      component during exercise was significantly ( P<0.05) greater in group P than in
      group E when expressed as an absolute value [mean (SEM)=77 (17) ml min(-1) and 24
      (16) ml min(-1)] and when normalised to end-exercise oxygen uptake, VO(2) [8.2
      (0.5)% and 2.6 (1.8)%]. Group differences were observed for percentage force loss
      during the electrical stimulation protocol [50.0 (3.4)% and 31.5 (3.7)% for
      groups P and E, respectively], increase in relaxation time from start to end of
      the fatigue test [87.9 (15.5)% and 31.1 (11.9)%], and relaxation time for fresh
      muscle [32.4 (1.0) ms and 40.6 (2.1) ms]. These contractile parameters may
      indicate a higher proportion of type II fibres in group P compared with group E.
      These experiments have shown evidence of a relationship between the amplitude of
      the slow component and muscle contractile properties, indicating that the origin
      of the slow component may lie in the pattern of different muscle fibre types.

PMID- 14677070
TI  - Vesicular glutamate transporter 2 is expressed in different nerve fibre
      populations that selectively contact pulmonary neuroepithelial bodies.
AB  - Pulmonary neuroepithelial body (NEB) receptors in rats receive at least four
      different nerve fibre populations. In addition to a spinal sensory innervation
      that contacts NEBs at their basal side, extensive vagal nodose sensory terminals
      and separate nitrergic and cholinergic nerve endings protrude between NEB cells.
      In the present study, antibodies against the vesicular glutamate transporter 2
      (VGLUT2), a transmembrane protein responsible for loading glutamate into synaptic
      vesicles, were used to investigate whether some of the nerve terminals contacting
      NEBs in rat lungs might use glutamate as a neurotransmitter. VGLUT2
      immunoreactivity (IR) was detected in extensive intraepithelial arborising nerve
      terminals that appeared to contact most of the NEBs. Multiple immunostaining
      showed VGLUT2 IR in the vagal nodose and spinal sensory nerve terminals
      contacting NEBs, and in another, most likely sensory, intraepithelial nerve fibre
      population, the origin and further characteristics of which remain to be
      elucidated. At least part of the VGLUT2-immunoreactive nerve fibres that contact
      NEBs were shown to be myelinated. The expression of VGLUT2 indicates that
      glutamate is stored and released as a neurotransmitter in terminals of several
      pulmonary (sensory) nerve fibre populations that selectively relate to the
      complex NEB receptors. The present study strongly suggests an involvement of
      glutamatergic mechanisms in the peripheral transduction of sensory stimuli from
      the lungs, via the release of glutamate from nerve terminals, thereby modulating
      the activity of NEB receptor cells or the excitability of afferent nerves.

PMID- 14677071
TI  - Perspectives of neuroscience in psychiatry.

PMID- 14677072
TI  - Molecular brain imaging and the neurobiology and genetics of schizophrenia.
AB  - It has been hypothesized that schizophrenia is related to dysfunction in
      temporolimbic-prefrontal neuronal networks, which is acquired early in an
      individual's development. After puberty, relatively reduced prefrontal control of
      striatal dopaminergic neurotransmission may lead to unmodulated striatal dopamine
      (DA) activity, and the positive symptoms of acute psychosis. Brain imaging
      studies support the notion of prefrontal dysfunction in schizophrenia and
      correlated upregulation of presynaptic striatal DA activity. Recent molecular
      brain imaging studies have combined genetic assessments with a multimodal
      neuroimaging approach to further refine our understanding of the pathophysiologic
      architecture of the disorder. We review the literature on functional brain
      imaging in schizophrenia and discuss genotype effects on core psychotic symptoms.
      A promising research strategy is the identification of genetic and environmental
      factors that contribute to intermediate phenotypes such as working memory
      deficits in schizophrenia. Molecular brain imaging can help to unravel the
      complex interactions between genes and environment and its association with
      neuronal network dysfunction in schizophrenia.

PMID- 14677073
TI  - Regio entorhinalis in schizophrenia: more evidence for migrational disturbances
      and suggestions for a new biological hypothesis.
AB  - Recently we were able to replicate the original finding of migrational
      disturbances in the entorhinal cortex (ERC) of schizophrenic patients by
      measuring the distance of pre-alpha cell clusters to the pial surface. In order
      to replicate this finding, we performed a detailed analysis of the pre-alpha cell
      clusters in the ERC in post mortem brains of 22 schizophrenic patients and 15
      control subjects. Cluster position relative to gray/white matter boundary were
      measured and normalized by the widths of the gray matter. In the ERC the pre
      alpha cell clusters were situated significantly closer to the gray/white matter
      junction compared to normal controls (around 30 %, F = 9.52, p = 0.004). No
      specific effects of sex, age or region of investigation were found. In summary,
      this is another quantitative replication of pre-alpha cell cluster migrational
      disturbances in schizophrenia, which are possibly linked to neurobiological
      abnormalities, e.g. myeloarchitectonic changes. This supports the notion that
      developmental abnormalities are a core feature of schizophrenia and that the
      search for candidate genes has to include this aspect, too. However, it is very
      probable that vulnerability-associated changes - as outlined here - have to be
      distinguished from disease-related changes.

PMID- 14677074
TI  - Early detection and intervention in the initial prodromal phase of schizophrenia.
AB  - Attenuated and transient psychotic symptoms as well as a combination of different
      risk indicators and a recent significant deterioration in global functioning are
      currently used as a preliminary definition of the initial prodromal or at-risk
      mental state by the vast majority of investigators in research on early psychosis
      detection and intervention. Recently published results demonstrated a mean
      progression to frank psychosis within one year in 36.7 % of cases showing
      emerging symptoms, indicating that these criteria already seem to provide a
      satisfying assessment for risk of an imminent psychosis. However, as functional
      decline often sets in before this time, detection in earlier prodromal stages
      seems necessary. In a prospective study, certain basic cognitive and perceptive
      symptoms showed good to excellent predictive accuracy for schizophrenic
      psychosis, thus potentially offering a reasonable approach for earlier detection.
      Early intervention is aimed at improving prodromal symptoms, avoiding functional
      deterioration, and suppressing or delaying transition to psychosis. Initial study
      results targeting an earlier or later prodromal phase are promising, but longer
      follow-ups and larger samples are needed.

PMID- 14677075
TI  - Modern treatment concepts in schizophrenia.
AB  - On the basis of available practice guidelines for schizophrenia, contemporary
      treatment principles for schizophrenia leading to phase- or stage-oriented,
      multidimensional treatment approaches are described. Additionally, based on
      current research programmes, future treatment developments are presented.

PMID- 14677076
TI  - Anhedonia, self-experience in schizophrenia, and implications for treatment.
AB  - Anhedonia - the inability to experience pleasure - is a symptom of several
      psychiatric disorders such as depression, drug and alcohol dependence, but also
      schizophrenia. The concept of anhedonia played a major role in psychiatric and
      psychoanalytic explanations of psychotic behavior. The relationship between
      notions of anhedonia and of mental evolution and regression (in the work of
      Myerson and Bleuler) is discussed. The non-evolutionist views of Rado and Meehl
      are described. Then the concept of anhedonia is discussed in relationship to the
      phenomenological approach of Sass and Parnas, who view anhedonia as one
      manifestation of a self-disturbance or self-disorder that is fundamental in
      schizophrenia. Concerning treatment of anhedonia, it was often hypothesized that
      anhedonia is associated with a dysfunction of the mesolimbic dopaminergic reward
      system. However, studies in humans and non-human animal models indicate that
      dysfunction of central dopaminergic neurotransmission interferes with the process
      of motivation rather than with the ability to experience pleasure; the latter may
      be more mediated by the opioidergic and serotonergic neurotransmission.
      Understanding the neurobiological correlates of motivation and pleasure may
      provide new options to treat anhedonia in patients with schizophrenia.

PMID- 14677077
TI  - Subjective well-being and initial dysphoric reaction under antipsychotic drugs -
      concepts, measurement and clinical relevance.
AB  - Since the introduction of neuroleptics in 1952, many studies have examined
      objective aspects of efficacy and tolerability. Despite the fact that neuroleptic
      treatment should also improve the patient's subjective experiences, this outcome
      criterion has been neglected in the past. This is unfortunate, as subjective well
      being with treatment appears to be strongly related to patients' readiness to
      take their medication. The few existing studies differ in methodology and are
      difficult to compare due to a number of weaknesses, including varying underlying
      concepts, used assessment scales, or small sample sizes. Negative subjective well
      being may manifest itself throughout the entire neuroleptic treatment, even as
      early as in the first 48 hours after neuroleptic treatment starts (initial
      dysphoric reaction, IDR). The aetiology of reduced subjective well-being or IDR
      is not fully explained; neuroleptic side effects, especially affective, cognitive
      and motor adverse events, differential effects of varying psychopathology or
      biopsychosocial are factors in discussion. The clinical impression is
      characterised by symptoms as dysphoria/anhedonia, reduced vitality, and emotional
      indifference, which could have a negative impact on relevant clinical factors
      such as response or medication adherence, and therefore on outcome. With regard
      to pharmacological treatment, evidence suggests that atypical antipsychotics
      induce less negative subjective effects than conventional neuroleptics, and that
      various new-generation antipsychotics could be evaluated differently by patients.
      This article reviews existing literature in order to approach relevant questions
      for pharmacotherapy.

PMID- 14677078
TI  - The influence of gender and emotional valence of visual cues on FMRI activation
      in humans.
AB  - Emotional neuroscience maps neurocircuits associated with the processing of
      affective stimuli. To assess gender differences in brain activation elicited by
      affective stimuli, we used pictures from the International Affective Picture
      System in a functional magnetic resonance imaging (fMRI) study. Ten male and ten
      female age-matched healthy volunteers were included and viewed affectively
      negative versus positive pictures, which were presented in an event related
      design. There was a significant interaction between valence of emotional stimuli
      and gender in the sublenticular extended amygdala (SLEA) and the rostral anterior
      cingulate. fMRI activation in these regions was stronger for negative compared to
      positive cues in women. In men fMRI activation was independent of stimulus
      valence. These results suggest to take gender differences into account when
      emotional paradigms are tested in functional brain imaging.

PMID- 14677079
TI  - Genetics of schizophrenia and affective disorders.
AB  - The molecular-genetic basis of non-mendelian, genetically influenced disorders
      (complex disorders) is beginning to be uncovered. Recently, major progress in
      localization and detection of disposition genes of schizophrenia and bipolar
      disorder was achieved. We provide a comprehensive overview of recent results of
      linkage and association studies in schizophrenia and bipolar disorder. Several
      disposition genes for schizophrenia (DTNBP1, NRG1, G72) were identified, whereas
      evidence for specific disposition genes in bipolar disorder is more limited.
      Multiple limitations of current research strategies in the search of disposition
      genes of complex disorders have to be considered; alternative phenotype
      definitions, genome-wide association studies and parallel investigation of
      epigenetic misregulations might overcome these limitations.

PMID- 14677080
TI  - Neurotransmitter changes by interferon-alpha and therapeutic implications.
AB  - Interferon alpha (IFN-alpha) is a cytokine that is widely used for the treatment
      of chronic viral infection or malignant disorders. During treatment with IFN
      alpha, severe neuropsychiatric syndromes may occur such as depression with
      suicidal ideation, paranoid psychoses or confusional states. The neurobiological
      correlates of these side effects are widely unknown. Besides induction of other
      cytokines and hormonal changes, IFN-alpha  has been shown to modulate the opioid,
      serotonin, dopamine and glutamate neurotransmitter system. Positive therapeutic
      effects of antidepressants such as selective serotonin-reuptake-inhibitors (SSRI)
      or of opioid receptor antagonists support the hypothesis that neurotransmitter
      changes play an important role in the development of IFN-alpha associated
      neuropsychiatric side effects. We review recent research about IFN-associated
      neurotransmitter changes in the central nervous system and discuss treatment
      strategies.

PMID- 14677081
TI  - Stress responsive neurohormones in depression and anxiety.
AB  - Clinical and preclinical studies have gathered substantial evidence that stress
      response alterations play a major role in the development of major depression,
      panic disorder and posttraumatic stress disorder. The stress response, the
      hypothalamic pituitary adrenocortical (HPA) system and its modulation by CRH,
      corticosteroids and their receptors as well as the role of natriuretic peptides
      and neuroactive steroids are described. Examplarily, we review the role of the
      HPA system in major depression, panic disorder and posttraumatic stress disorder
      as well as its possible relevance for treatment. Impaired glucocorticoid receptor
      function in major depression is associated with an excessive release of
      neurohormones, like CRH to which a number of signs and symptoms characteristic of
      depression can be ascribed. In panic disorder, a role of central CRH in panic
      attacks has been suggested. Atrial natriuretic peptide (ANP) is causally involved
      in sodium lactate-induced panic attacks. Furthermore, preclinical and clinical
      data on its anxiolytic activity suggest that non-peptidergic ANP receptor ligands
      may be of potential use in the treatment of anxiety disorders. Recent data
      further suggest a role of 3alpha-reduced neuroactive steroids in major
      depression, panic attacks and panic disorder. Posttraumatic stress disorder is
      characterized by a peripheral hyporesponsive HPA-system and elevated CRH
      concentrations in CSF. This dissociation is probably related to an increased risk
      for this disorder. Antidepressants are effective both in depression and anxiety
      disorders and have major effects on the HPA-system, especially on glucocorticoid
      and mineralocorticoid receptors. Normalization of HPA-system abnormalities is a
      strong predictor of the clinical course, at least in major depression and panic
      disorder. CRH-R1 or glucorticoid receptor antagonists and ANP receptor agonists
      are currently being studied and may provide future treatment options more closely
      related to the pathophysiology of the disorders.

PMID- 14677082
TI  - Thyroid, brain and mood modulation in affective disorder: insights from molecular
      research and functional brain imaging.
AB  - The efficacy resulting from adjunctive use of supraphysiological doses of
      levothyroxine has emerged as a promising approach to therapy and prophylaxis for
      refractory mood disorders. Most patients with mood disorders who receive
      treatment with supraphysiological doses of levothyroxine have normal peripheral
      thyroid hormone levels, and also respond differently to the hormone and tolerate
      it better than healthy individuals and patients with primary thyroid diseases.
      Progress in molecular and functional brain imaging techniques has provided a new
      understanding of these phenomena, illuminating the relationship between thyroid
      function, mood modulation and behavior. Thyroid hormones are widely distributed
      in the brain and have a multitude of effects on the central nervous system.
      Notably many of the limbic system structures where thyroid hormone receptors are
      prevalent have been implicated in the pathogenesis of mood disorders. The
      influence of the thyroid system on neurotransmitters (particularly serotonin and
      norepinephrine), which putatively play a major role in the regulation of mood and
      behavior, may contribute to the mechanisms of mood modulation. Recent functional
      brain imaging studies using positron emission tomography (PET) with [ (18)F]
      fluorodeoxyglucose demonstrated that thyroid hormone treatment with levothyroxine
      affects regional brain metabolism in patients with hypothyroidism and bipolar
      disorder. Theses studies confirm that thyroid hormones are active in modulating
      metabolic function in the mature adult brain, and provide intriging neuroanatomic
      clues that may guide future research.

PMID- 14677083
TI  - Algorithms for optimizing the treatment of depression: making the right decision
      at the right time.
AB  - Medication algorithms for the treatment of depression are designed to optimize
      both treatment implementation and the appropriateness of treatment strategies.
      Thus, they are essential tools for treating and avoiding refractory depression.
      Treatment algorithms are explicit treatment protocols that provide specific
      therapeutic pathways and decision-making tools at critical decision points
      throughout the treatment process. The present article provides an overview of
      major projects of algorithm research in the field of antidepressant therapy. The
      Berlin Algorithm Project and the Texas Medication Algorithm Project (TMAP)
      compare algorithm-guided treatments with treatment as usual. The Sequenced
      Treatment Alternatives to Relieve Depression Project (STAR*D) compares different
      treatment strategies in treatment-resistant patients.

PMID- 14677084
TI  - Lithium augmentation in treatment-resistant depression: clinical evidence,
      serotonergic and endocrine mechanisms.
AB  - For now more than 50 years, lithium has been the gold standard for the
      pharmacologic treatment of bipolar disorder. However, its utility is not
      restricted to acute mania and prophylactic treatment of bipolar disorder. A
      relatively new indication for its use is the addition to an antidepressant in the
      acute treatment phase of unipolar major depression. To date, this treatment
      approach called lithium augmentation is the best-documented approach in the
      treatment of refractory depression. In international treatment guidelines and
      algorithms, lithium augmentation is considered a first-line treatment strategy
      for patients with a major depressive episode who do not adequately respond to
      standard antidepressant treatment. In a recent double-blind, placebo-controlled
      trial, lithium augmentation has demonstrated to also be effective in the
      continuation treatment phase to prevent early relapses. From animal studies there
      is robust evidence that lithium augmentation increases serotonin (5-HT)
      neurotransmission, possibly by a synergistic action of lithium and the
      antidepressant on brain 5-HT pathways. In contrast to the established decline of
      HPA system activity during treatment with tricyclic antidepressants,
      neuroendocrine studies on the effects of lithium augmentation on the HPA system
      showed an unexpected and marked increase in the ACTH and cortisol response in the
      combined DEX/CRH test. Here we review new data on the efficacy and mechanism of
      action of lithium augmentation.

PMID- 14677085
TI  - Individualized medicine - implementation of pharmacogenetic diagnostics in
      antidepressant drug treatment of major depressive disorders.
AB  - Antidepressant drug therapy is characterized by a high rate of therapeutic
      failure. There is increasing evidence that genetic factors are contributing to
      the inter-individual variability in antidepressant drug response. Genetic
      variability is described in both the pharmacokinetic part of drug action as well
      as in pharmacodynamic structures mediating drug effects. Genetic polymorphisms in
      drug metabolizing enzymes are well characterized and have large effects on oral
      clearances or elimination half-lives of antidepressant drugs. These differences
      can be compensated by adapting the individual dose to genotype in addition to
      other factors such as gender, weight, age, liver and kidney function. On the part
      of drug action, genetic variability is described in molecular structures of
      antidepressant effects. Several studies on response of antidepressants have
      revealed influences of polymorphisms in neurotransmitter receptors and
      transporters changing sensitivity of patients to treatment with antidepressants;
      however, results were often contradictory. A pharmacogenomic approach to
      individualize antidepressant drug treatment is recommended to be based on several
      levels: 1) identifying and validating the candidate genes involved in drug
      response; 2) providing therapeutic guidelines; and 3) developing a
      pharmacogenetic test-system for bedside-genotyping.

PMID- 14677086
TI  - The electronic assessment of the longitudinal course of bipolar disorder: the
      ChronoRecord software.
AB  - Longitudinal studies are the optimal approach when investigating the highly
      variable course of bipolar disorder, but such studies are expensive, prone to
      reporting errors and to missing data. Automation of data collection may reduce
      such errors and improve data quality. The ChronoRecord, validated software that
      patients can install on a home computer to report mood, medications, sleep, life
      events, weight and menstrual data, has been designed to achieve such automation.
      In the trial of the ChronoRecord reported here, 80 of 96 (83 %) patients with
      bipolar disorder showed high acceptance of this computer-based system for self
      report, entering daily recordings for a period of 3-months. This new technology,
      in addition to providing an accurate longitudinal record for research purposes,
      also facilitates on-going patient feedback and accurate study monitoring.

PMID- 14677087
TI  - Implications of the neuroprotective effects of lithium for the treatment of
      bipolar and neurodegenerative disorders.
AB  - Bipolar disorder is increasingly recognized as an illness that may progress to
      impairment in neurocognitive functioning and cell loss in cortical and limbic
      brain regions. Glutamatergic damage and/or damage due to high glucocorticoid
      levels that inhibit adult neurogenesis are likely contributing mechanisms. Drug
      treatments with possible neuroprotective effects are becoming increasingly
      important both clinically and as research tools. Mood stabilizing drugs and
      lithium in particular may act to prevent neuronal damage and tissue loss that may
      occur in the brain of patients with bipolar disorders. Lithium has been shown to
      exert neuroprotective effects in vitro and to stimulate neurogenesis in the
      hippocampus. Animal studies have demonstrated pharmacological effects of lithium
      suggestive of its role in neuroprotection, which range from reducing
      excitotoxicity through increased glutamate uptake, to regulation of a number of
      signal transduction intermediates such as myo-inositol, protein kinase C,
      phosphotidylinositol-3 kinase (PI-3K)/protein kinase B (Akt), ras-mitogen
      activated protein kinase (MAPK), glycogen synthase kinase (GSK)-3alpha and -3beta
      and calcium. It remains to be established whether lithium treatment protects
      against possible cell damage in the same manner as it protects against
      recurrences of the illness. We propose to examine the effect of long-term lithium
      treatment on neurocognitive functioning of bipolar patients and the use of
      lithium in the treatment of chronic neuropsychiatric disorders.

PMID- 14677088
TI  - Neurobiological correlates of the disposition and maintenance of alcoholism.
AB  - The last decade witnessed a rapid increase in the knowledge of the etiopathology
      and treatment of alcoholism. The current disease concept includes psychosocial
      and neurobiological foundations and consequences of alcoholism. Neurobiological
      research points to dispositional factors such as a low level of response to
      alcohol, which is partly heritable and seems to be associated with monoaminergic
      dysfunction and reduced GABAergic alcohol effects. Chronic alcohol intake
      stimulates counteradaptive neuroadaptation in central GABAergic and glutamatergic
      neurotransmission, which increases alcohol tolerance. Neuroadaptation to chronic
      alcohol effects is not immediately reversed during detoxification and can cause
      clinical withdrawal once alcohol intake is terminated. Sensitization of the
      dopaminergic and opioidergic reward system may contribute to alcohol craving and
      reduced control of alcohol intake. New treatment options include pharmacological
      approaches and indicate that behavior or motivational therapy and the attendance
      of patient groups may equally reduce the relapse risk.

PMID- 14677089
TI  - [Transferring disease-oriented basic research into pediatric oncology].

PMID- 14677091
TI  - Proteomics: techniques and applications in cancer research.
AB  - Proteomics can be defined as functional analysis of the full set of proteins by
      high-throughput technologies in a given system. The workflow of proteomics is a
      multi-step process comprising sample preparation, separation, quantification and
      identification of proteins. Due to the high complexity of different protein
      species and the wide dynamic range of protein amount within a cell system it is
      necessary to apply appropriate analysis methods. One approach is to separate
      proteins first by two-dimensional gel electrophoresis (2-DE) according to charge
      and molecular weight. Proteins are then fragmented and analyzed using matrix
      assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF
      MS). Identification of proteins can be achieved by comparing the mass/charge
      ratios of these peptides to respective databases. Proteome analysis with respect
      to the identification of disease-associated patterns of molecules in different
      tissues is in the early stages, because standardisation of these techniques often
      remains to be established. However, proteome analyses is a promising tool to
      obtain holistic insights into the physiological status of a cell or cellular
      system. Compared to RNA-based studies some advantages are obvious: (1) post
      translational modifications, e. g. phosphorylation, contributing to the activity
      status can be detected at the protein level only, (2) RNA-levels do not
      necessarily coincide with protein levels for a particular gene, (3) feedback
      mechanisms within regulatory pathways can control protein activity without
      measurable changes in mRNA content.

PMID- 14677092
TI  - Microarray-analysis: a new approach to study the molecular mechanisms of thermo
      chemotherapy.
AB  - BACKGROUND: Experimental studies for the treatment of relapsed neuroblastoma
      include the use of hyperthermia in combination with chemotherapeutic drugs.
      Cytotoxic effects of alkylants and platinum compounds on tumor cells can be
      enhanced by hyperthermia in various in vitro models. However, the underlying
      molecular mechanisms are still largely unknown. METHOD: In this study, we used
      microarray-analysis as a new biological approach to gain insight into the
      pharmacogenomics and possible target genes of thermochemotherapy. As a model, LAN
      1 neuroblastoma cells were treated for 1 h with low doses of cisplatin alone,
      with simultaneous heating to 42 degrees C or with hyperthermia alone. Gene
      expression was analyzed at five time points 0 to 24 h after treatment using
      U95Av2 oligonucleotide arrays (Affymetrix Inc). Significant changes of gene
      expression levels were calculated by similarity metrices and Pearson correlation.
      RESULTS: Only a few genes (n = 23) demonstrated altered expression following
      treatment of LAN 1 cells with cisplatin alone. Hyperthermia alone resulted in
      significant expression changes of 136 genes in comparison to untreated control
      cells. Combination therapy of cisplatin and hyperthermia resulted in expression
      changes of 251 genes, interestingly including 131 genes with unchanged expression
      under treatment with either cisplatin or hyperthermia alone. Significant changes
      of expression levels could be annotated to genes involved in heat shock response,
      protein degradation and apoptosis. These results are now being validated on mRNA-
      and protein levels by RT-PCR and Western Blot analysis. CONCLUSION: Microarray
      Analysis is a suitable new approach for the identification of target genes, which
      might play an important role for the synergistic effect of hyperthermia and
      chemotherapy in tumor cells.

PMID- 14677093
TI  - An approach for cure: PEI-chemotherapy and regional deep hyperthermia in children
      and adolescents with unresectable malignant tumors.
AB  - BACKGROUND: Elevated temperatures of 40 - 44 degrees C increase the actions of
      various anticancer drugs including N-lost derivatives, cytotoxic antibiotics and
      platinum analoga. In clinical usage thermochemotherapy (TCH) should facilitate
      surgical resection and ameliorate local tumor control. PATIENTS AND METHODS: From
      07/1993 to 12/2002 a total of 39 patients have been enrolled onto a phase-II
      study (female = 24, male = 15, age 1 - 37.5 years, median 5.2). Among these, 24
      patients had extracranial non-testicular germ cell tumors and 15 patients soft
      tissue or chondrosarcomas. INDICATION: locoregional relapse (n = 29) or
      unresectable tumor after neoadjuvant chemotherapy (n = 10). Among these two
      groups, there were ten patients with poor response or progressive disease under
      primary or relapse chemotherapy. Ten out of the 29 relapse patients had more than
      one relapse. Tumor site: pelvis (30), abdomen (4), head and neck (2), proximal
      leg (2) and lumbar spine (1). Thermochemotherapy (TCH): 1800 - 2000 mg
      ifosfamide/m (2) and 100 mg etoposide/m (2) on days 1 - 4 and 40 mg cisplatin/m
      (2) on days 1 + 4 combined with regional deep hyperthermia (42 - 44 degrees C, 1
      h) on days 1 + 4. RESULTS: In 39 protocol patients a total of 166 TCH courses
      (332 heat sessions) were applied. 20 patients achieved complete response, and 10
      patients achieved partial response. TCH was followed by surgical tumor resection
      in 28/39 patients and/or radiotherapy in 13/39 patients. At a median follow-up of
      27 months, outcome in this high-risk patient population was 22 NED, 3 AWD, 12
      DOD, 2 DOC. Five year event free (EFS) and overall survival (OS) for the whole
      study cohort was 0.39 +/- 0.11 (20/39 patients) and 0.52 +/- 0.11 (25/39
      patients), respectively. CONCLUSION: TCH shows substantial therapeutic efficacy
      and facilitates complete tumor resection in 14 out of 28 operated patients.
      Multimodal treatment including TCH, surgical resection and/or radiotherapy leads
      to sustained remission in the majority of patients with locoregional tumor
      recurrence. The therapeutic effect is most pronounced, if TCH is administered at
      first relapse. Due to the clinical and histologic heterogeneity the number of
      patients eligible for TCH is limited. Therefore, a more valid assessment of
      treatment efficacy can only be made by a matched-pair comparison in cooperation
      with the clinical registers.

PMID- 14677094
TI  - Functional capacity, obesity and hypothalamic involvement: cross-sectional study
      on 212 patients with childhood craniopharyngioma.
AB  - The aim of this study was to analyze the impact of hypothalamic involvement of
      craniopharyngioma on functional capacity (FC) and obesity in 212 patients with
      childhood craniopharyngioma. FC could be evaluated using an ability scale
      (Fertigkeitenskala Munster-Heidelberg [FMH]) in 174 patients with childhood
      craniopharyngioma. Obesity was quantified in 212 patients at the time of
      diagnosis and at the time of latest evaluation by body mass index SDS [BMI]. The
      influence of hypothalamic tumor involvement on FC and BMI was analyzed. Patients
      with hypothalamic involvement (n = 125) presented with higher BMI SDS at the time
      of diagnosis (p = 0.001) and at latest follow-up evaluation (p < 0.001). FC as
      measured by FMH percentiles was lower (p < 0.001) in patients with hypothalamic
      involvement when compared with patients without hypothalamic involvement. FC
      negatively correlated (p < 0.001) with BMI SDS (Spearman's Rho = -0.40) only in
      patients with hypothalamic involvement whereas no correlation between FC and BMI
      SDS was found in patients without hypothalamic involvement. We conclude that
      hypothalamic involvement of childhood craniopharyngioma had major impact on FC in
      survivors. Obesity resulted in impaired FC of patients with hypothalamic
      involvement. BMI at diagnosis was a sensitive parameter to identify patients at
      risk of severe obesity. Further analysis on this issue is performed in the
      prospective, multicenter surveillance study on children and adolescents with
      craniopharyngioma (KRANIOPHARYNGEOM 2000).

PMID- 14677095
TI  - Immunodeficiency and Hodgkin's disease: treatment and outcome in the DAL HD78-90
      and GPOH HD95 studies.
AB  - BACKGROUND: Excellent treatment results have been obtained for children with
      Hodgkin's disease (HD). Children with immunodeficiencies who present with HD do
      not have such a favourable prognosis. PATIENTS AND METHODS: A systematic
      literature search using MEDLINE and a search for immunodeficiencies in the
      database of the trials DAL HD78-HD90 and GPOH HD95 (n = 2263) were carried out.
      Age, sex, type of immunodeficiency, disease stage, treatment and outcome of all
      HD cases with known immunodeficiency were recorded. RESULTS: 28 published cases
      and 13 children in the DAL/GPOH trials were identified. 19/28 and 6/13 patients
      have immunodeficiencies with increased DNA breakage (24/25 ataxia
      teleangiectasia, 1/25 Nijmegen breakage syndrome) who present largely with stage
      III - IV HD. Among the published cases with increased DNA breakage there is only
      one child who is surviving 16 months after diagnosis, while there are 6/9
      survivors in the group of immunodeficiencies without increased DNA breakage.
      Similarly, only 1/6 children survives in the group of children reported to the
      DAL/GPOH trials suffering from HD and immunodeficiency with increased DNA
      breakage, while the outcome in children suffering from immunodeficiency without
      increased DNA breakage is much better with 5/7 survivors. CONCLUSIONS: The
      literature review and data analysis of the DAL/GPOH studies show that treatment
      outcome is almost invariably fatal in children with HD and immunodeficiency with
      increased DNA breakage. Thus we propose to treat children with or without
      increased DNA breakage differently to improve the outcome of Hodgkin's disease in
      the subgroup of children with immunodeficiency.

PMID- 14677096
TI  - Effects of dose-reduced Medac L-asparaginase on coagulation in trial ALL-BFM
      2000.
AB  - BACKGROUND: Glucocorticoids and L-asparaginase (L-ASP) are essential elements of
      contemporary chemotherapy of childhood acute lymphoblastic leukemia (ALL). Both
      cytotoxic drugs are well-known to induce significant alterations in hemostasis,
      especially affecting the inhibitors of coagulation including antithrombin III (AT
      III), protein C and protein S. PATIENTS AND METHODS: The objectives of the
      present prospective study were to analyze the course and degree of the changes of
      several coagulation proteins during induction therapy of 16 patients treated
      according to the Berlin-Frankfurt-Munster (BFM) ALL protocol 2000. The induction
      protocol included a 7-day mono-therapy with glucocorticoids followed by 4 weeks
      with additional vincristine, daunorubicin and E. coli L-ASP (Medac) which was
      administered at a dosage of 5000 IU/m (2) 8-times at 3-day intervals. RESULTS AND
      CONCLUSIONS: This analysis is the first to show that 5000 IU/m (2) of the Medac L
      ASP leads to a less pronounced decrease of the plasma AT III and fibrinogen
      concentrations during induction therapy (after the 5 (th) L-ASP dose), as
      compared to previous BFM protocols which used the Medac L-ASP in a dosage of 10
      000 IU/m (2). Our results confirmed that following a mono-therapy with
      glucocorticoids the AT III, protein C and protein S levels increased while the
      fibrinogen level decreased. As the D-Dimers remained within the normal range
      during the 3 weeks of L-ASP combination chemotherapy and none of the patients
      suffered a thromboembolic event, we also concluded that despite of the
      significant decrease of anticoagulant proteins, there might be a balance between
      coagulation and fibrinolysis; thus the D-Dimers may eventually serve as a helpful
      indicator for therapeutic interventions.

PMID- 14677097
TI  - Methylenetetrahydrofolate reductase gene polymorphism and glucocorticoid intake
      in children with ALL and aseptic osteonecrosis.
AB  - BACKGROUND: Methotrexate is an essential part of the treatment of acute
      lymphoblastic leukaemia (ALL). Due to an increased survival of ALL patients,
      complications like BME (bone marrow edema) and AON (aseptic osteonecrosis) have
      become a matter of increasing importance. The aim of the study was to find out if
      a polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene
      predisposes to the development of BME and/or AON. Furthermore the cumulative
      prednisone equivalent dose per kilogram body weight was compared in a matched
      pairs analysis. PATIENTS AND METHODS: A retrospective analysis of the MTHFR
      polymorphism of 87 patients was performed (48 male, 43 female). 14/87 patients
      were diagnosed with BME and/or AON (16 %). RESULTS: 42/73 patients without BME
      and/or AON (43 male, 34 female, median age 5.3 yrs) and 10/14 patients with
      BME/AON (5 male, 9 female, median age 10.2 years) presented with a MTHFR
      polymorphism (p = 0.28). 14,3 % of the patients with MTHFR-polymorphism but
      without BME and/or AON (6/42) and 70 % of the patients with MTHFR-polymorphism
      and with BME and/or AON (7/10) were over 10 years of age at ALL diagnosis (p =
      0.002). The mean cumulative prednisone equivalent dose per kilogram body weight
      was 98.0 mg, compared with 100.0 mg in the matched pairs group. CONCLUSIONS: The
      age of the patients at diagnosis seems to be a risk factor for the development of
      BME and/or AON as also seen in previous studies. If MTHFR polymorphism is an
      additional risk factor it was not borne out by this study, possible due to the
      small number of patients analyzed. This aspect is worth to be proven with a large
      group of patients considering the MTX pharmacokinetic and leucovorine rescue.

PMID- 14677098
TI  - Joint preserving surgery for osteonecrosis and osteochondral defects after
      chemotherapy in childhood.
AB  - BACKGROUND: As a complication of chemotherapy/corticosteroids for the treatment
      of acute lymphoblastic leukemia (ALL) and other malignancies during childhood,
      avascular osteonecrosis appears in up to 30 % of the patients. Weight-bearing
      joints are involved in over 90 % of the cases. Total joint replacement is often
      necessary to restore function. Yet, endoprostheses in young patients again bare
      the risk of later complications and the need for several revision surgeries. In
      this report, joint preserving surgical strategies will be discussed. PATIENTS:
      Three hips and eleven knee joints in 8 patients (4 male, 4 female) were operated
      on for symptomatic ON and/or osteochondral defects (OCD) after chemotherapy. Four
      of the patients underwent surgery in more than one joint. The average age at the
      time of surgery was 18 years (range 14 - 26). The procedures included retrograde
      drilling (core decompression), bone grafting, implantation of collagen sponges
      with autologous bone marrow aspirate, osteochondral autograft transplantation and
      transplantation of periosteal flaps. Two hip joints underwent total joint
      replacement. Average follow up was 25 months. RESULTS: After an average follow up
      of 2 years, all patients were satisfied with the functional results after the
      last follow up with pain free walking for a minimum of 60 minutes. No night pain
      was reported. One patient complained about intermittent periods of dysaesthesia
      around the bone harvest area at the iliac crest. CONCLUSIONS: The aim of surgery
      for ON and OCD after chemotherapy should be the reduction of pain and
      preservation of the joint to bypass the risks of joint replacement in young
      patients, although total joint replacement may become indicated in endstage
      degeneration of the involved joint.

PMID- 14677099
TI  - [Quality management within the competence network of paediatric oncology and
      haematology].
AB  - The competence network paediatric oncology and haematology aims at improving the
      structure of paediatric oncology and haematology as a whole focussing in
      particular on the quality of clinical trials and study centres. This implicates
      the following measures: (1) Employment of research and trial assistants in order
      to improve the quality of documentation and study management in the participating
      hospitals. (2) Building up of an Internet portal to provide medical information
      for non-professionals, for patients and their families as well as for health
      professionals. (3) The project "Study Assistance" supports study centers during
      the process of writing and examining new treatment protocols so that they are in
      compliance with the Good Clinical Practice criteria, formal criteria and
      statutory provisions. It presently works on a structural standardisation of study
      protocols and case record forms in order to improve their usability. In addition,
      the working group "Quality Assurance in GPOH Study Centres" is engaged in
      developing a quality management system for study centers.

PMID- 14677100
TI  - [Quality standards and their assurance for study centers in the competence
      network malignant lymphoma].
AB  - BACKGROUND: The aim of most of the trials of the Competence Network Malignant
      Lymphoma is to optimize the standard treatment of lymphoma using only registered
      drugs in the case of medicinal therapies (quality assurance protocols). In
      contrast to regulatory trials, special regulations for quality assurance
      protocols are not given by the legislature. However, there is agreement that also
      for this type of studies the declaration of Helsinki and the Guidelines of the
      International Conference on Harmonisation (ICH) are relevant. The ICH Guidelines
      must be formulated to take into account the specific situation of quality
      assurance protocols and to ensure at the same time efficiency and transparency of
      these studies. This is the aim of the quality management of the study groups in
      the Competence Network Malignant Lymphoma. METHOD: The quality assurance measures
      already established in the study groups are being expanded to a comprehensive
      quality management concept in agreement with the ICH Guidelines and allowing for
      the situation of quality assurance protocols. To this end, a working group for
      quality management (AG-QM) has been set up to define and establish general
      quality standards for all aspects of planning, executing and evaluating quality
      assurance protocols in study centers. RESULTS: The AG-QM has developed a system
      of Standard Operating Procedures (SOPs) reflecting all working procedures of the
      study centers. Furthermore, evaluation parameters for the quality of trial
      execution have been identified and the harmonisation of documentation parameters
      has been initiated. Term definitions are collected and their harmonisation
      coordinated. CONCLUSIONS: Development of quality standards is the first step of
      quality management. To ensure the realisation of these standards in practice, the
      AG-QM will establish quality assurance measures including continuous reevaluation
      of quality criteria and actualization of quality standards if necessary.

PMID- 14677101
TI  - [10 years of computer-aided therapy planning in a department of pediatric
      hematology and oncology].
AB  - A computer program for the automated computation of chemotherapy has been
      introduced to a department of pediatric hematology and oncology. The program is
      used for about 700 treatments (100 patients) per year. On average, each physician
      performs 33 computations per year. Use of the program has greatly improved
      treatment safety, accompanied by a saving of about 50 minutes per computation, 30
      minutes for physicians, 20 minutes for nurses, respectively.

PMID- 14677102
TI  - [Analysis of paediatric neuro-oncological information on the Internet in German
      language].
AB  - BACKGROUND: The fast growing internet offers easy access to medical information.
      So far there are limited data concerning the quality of this information. This
      study examined quality and readability of paediatric neuro-oncological
      information on the internet in german language. METHOD: Using the search terms
      "medulloblastoma", "ependymoma", "craniopharyngeoma", "brainstem glioma" and "low
      grade astrocytoma" in six different search engines, the first 30
      universal/uniform resource locators (URLs) of each search engine were assessed.
      Appropriate Web sites were evaluated in regards to quality using DISCERN
      Instrument and checklist rating system. Readability was rated by Flesch Reading
      Ease score. RESULTS: Out of 889,56 web sites remained evaluable. Most of the
      sites rated as poor to very poor (49 %), 30 % rated as fair and 21 % as good to
      very good. Readability was scored as very difficult with complex vocabulary
      content limiting the usefulness of good web sites. CONCLUSIONS: Search-ing for
      childhood brain tumours via internet is time consuming and most often
      ineffective. There is a lack of high-quality and comprehensible information on
      childhood brain tumours on german web sites. Cooperation of scientific medical
      societies and the Federal Ministry of Health is essential to provide
      comprehensible and high-quality information on internet as an effective and
      supportive resource for patients and their relatives.

PMID- 14677103
TI  - [Evaluating the rehabilitation process by means of peer review: examination of
      the methods used and findings of the 2000/2001 data collection in the somatic
      indications].
AB  - This paper reports the results of a peer review system that was implemented in
      the context of the quality assurance programme of the statutory German Pension
      Insurance scheme. The data reported refer to the 2000/2001 data collection period
      for medical rehabilitation in the somatic indications. Examination of inter-rater
      reliability for judgements of individual raters shows satisfactory results only
      in orthopaedics. In the quality assurance programme, rehabilitation centres are
      usually evaluated by the mean of 20 rater judgements. The reliability of this
      aggregated measure is satisfactory in all indications. The results of 561
      rehabilitation centres show that those quality criteria are in particular need of
      improvement that refer to subjective concepts of patients (e. g., subjective
      theories of illness). Between peer review procedures in 1998 and 1999, the
      quality scores of rehabilitation centres had improved whereas between 1999 and
      2000/2001, no further improvement can be shown. However, those rehabilitation
      centres with a low quality score in 1999 (lowest quartile of the distribution)
      underwent a positive development between 1999 and 2000/2001. Reasons for this
      trend and possibilities for improving interrater reliability of the peer review
      process as an element of the quality assurance programme of the German Pension
      Insurance scheme are discussed.

PMID- 14677104
TI  - [The prognostic value of variables from the quality assurance program and of the
      rehabilitation-discharge report of the LVA Baden-Wurttemberg for early
      retirement: results of a retrospective cohort-study].
AB  - Since 1997 the LVA Baden-Wurttemberg pension insurance agency has implemented an
      instrument to measure the outcome quality of in-patient rehabilitation. The
      objective of this study was to evaluate the prognostic value of various short
      term rehabilitation success markers and of variables of the quality assurance
      program and the rehab-discharge report of the LVA Baden-Wurttemberg on early
      retirement by means of a retrospective cohort study. The analysis was based on
      routinely registered data of patients who underwent in-hospital rehabilitation in
      a hospital accredited by the LVA Baden-Wurttemberg between June 1997 and June
      1999. Baseline data included information from medical discharge reports and from
      the quality assurance programme. Follow-up information with regard to disability
      was collected until July 2000. The prognostic value of the quality assurance
      programme and of 4 standardized documented items from the medical discharge
      report was estimated by proportional hazards regression. In this analysis 6,823
      patients aged 30-59 years who underwent an in-patient rehab programme between
      June 1997 and July 1999 in 5 of 6 LVA rehab clinics were included. During follow
      up (mean duration: 1.8 years) 908 (13.3%) patients retired because of health
      related disability. The variables with the strongest prognostic values were the
      evaluation of the patient health status by the physician and the patients
      themselves and the capacity to work. The variables with the highest prognostic
      value were the evaluation on a 1-6 visual analogue scale; a better assessment by
      one mark of the health status by physician and patient himself, respectively, was
      associated with a 53% and 40% reduced risk of disability. Fitness for work at
      discharge was the most prognostic variable from the discharge report. Patients
      who were able to work had a 78% reduced risk of disability compared to patients
      unable to work. Also of prognostic relevance were a positive performance and the
      duration of the inability to work the year before rehabilitation. The variables
      of the newly developed quality assurance programme of the LVA clearly
      demonstrated a prognostic value in terms of risk for subsequent early retirement.
      It should be considered to include the ability to work at discharge in the
      programme to further improve its prognostic value.

PMID- 14677105
TI  - [The Comprehensive Cohort Design as alternative to the randomized controlled
      trial in rehabilitation research: advantages, disadvantages, and implementation
      in the SARAH study].
AB  - In rehabilitation research new therapies have to be evaluated within randomized
      trials as the best choice for proving the efficacy. Randomized controlled trials
      are widely accepted as the definitive method for evaluating the efficacy of new
      therapies. The random assignment of patients to their treatment ensures the
      internal validity of the comparison of new treatments with controls. Often
      patients in a randomized trial only represent a small proportion of the patients
      who satisfy the inclusion criteria of the trial. This will especially be true in
      rehabilitation medicine because of strong preferences of the patients for one or
      the other therapy. An assessment of the external validity of trial results can
      best be achieved by comparing the study population to the population of patients
      who met the eligibility criteria but did not consent to randomization. The
      Comprehensive Cohort Design (CCD) is designed to have the opportunity of
      recruiting all patients fulfilling these eligibility criteria regardless of their
      consent to randomisation. Advantages and disadvantages of this study design will
      be discussed in detail and on the example of the SARAH-study.

PMID- 14677106
TI  - [Who should decide on applications for medical rehabilitation? A critical
      reappraisal of the proposals of the Advisory Board on Concerted Action in Health
      Care].
AB  - Summary. In Germany the allocation of rehabilitation services depends on a
      decision of one of the social insurance funds. This decision is taken on the
      basis of an assessment of the application file by a physician of the fund. The
      general practitioner who may be the best informed professional as to the
      patients' disability, has no decision power in this allocation process. In 2001,
      however, the prestigious Advisory Board to the Ministry of Health proposed to
      leave the allocation to the general practitioner or another physician in office
      practice, thus restricting the role of the fund to verifying the appropriateness
      of the decision of the GP. This proposal is reviewed on the basis of the results
      of a survey among all general practitioners in the four Lander of Hamburg,
      Schleswig-Holstein, Mecklenburg-Vorpommern and Sachsen-Anhalt (n = 2110; response
      rate of 46%) done between 1999 and 2001. Furthermore, several steps and measures
      are proposed in view of increasing the involvement of the GP in the allocation
      process and of improving the communication between the funds and the general
      practitioners.

PMID- 14677107
TI  - [Allocation decisions of health insurance rehabilitation managers--An explorative
      case study concerning stroke rehabilitation].
AB  - We investigated processes of and subjective reasons for resource allocation in
      three out of four rehabilitation specialists of a regional office of a major
      health insurance. Decisions of health insurance personnel include approval of and
      duration of rehabilitation treatment and choice of clinical provider. Insurance
      specialists are mainly involved in documentation and coordination, whereas
      decisions mainly follow expert recommendations, mainly of the medical service.
      Allocation is based primarily on somatic impairment and disability, psychosocial
      function, motivation and rehabilitation potential are regarded as secondary.
      Goals and expected results of rehabilitation are neither individually defined nor
      their achievement evaluated. Decision processes are dominated by routines and
      agreements. Only exceptionally, defined rules and procedures are applied. Active
      case management is hampered by a highly specialized internal structure of the
      investigated insurance fund. The optimal fulfillment of individual requirements
      for a limited-time rehabilitation treatment is the central criterion for decision
      making. However, the specialists lack detailed information concerning
      appropriateness, quality and efficacy of rehabilitation providers, especially
      when taking patient-related variables into account. Instead, they trust that only
      high-quality institutions are contracted. Systematic control and feedback of
      rehabilitation results is not available. The surveyed rehabilitation managers do
      not include cost aspects in their decision-making. They would regard this as
      alien to a member- and patient-oriented policy. Improvement potentials with
      respect to rehabilitation case management are being reviewed.

PMID- 14677108
TI  - [Inpatient psychosomatic rehabilitation for Turkish migrants: what can be
      realized, what are the effects?].
AB  - A sample of 184 Turkish migrants who had been treated in a department for
      psychosomatic rehabilitation, were included in a study using retrospective
      analysis of their clinical documents. Somatoform disorders and depressions
      predominated among the main diagnoses but somatic diseases and risk factors were
      frequent as well. Because of insufficient outpatient treatment, diagnostic
      procedures concerning somatic state often became necessary during the
      rehabilitation measure, uncovering previously unknown somatic diseases in 16% of
      the patients. The main focus of the psychotherapy offered to the migrants had
      been slightly more on unburdening from suffering, also it included more psycho
      educational elements, but apart from this the quality and quantity of treatment
      hardly differed from a sample of German patients. Hence, though based on higher
      efforts and costs, the psychosomatic rehabilitation offered to the Turkish
      migrants had been implemented according to current standards. An important effect
      of inpatient rehabilitation seems to have been the working out of an overall
      therapeutic concept comprising all psychic and somatic problems. The very poor
      results in social-medical respects found in the study have with increasing
      experience been considerably improved in the meantime.

PMID- 14677109
TI  - [EEG-based communication--a new concept for rehabilitative support in patients
      with severe motor impairment].
AB  - This paper describes a paralyzed patient diagnosed with severe infantile cerebral
      palsy, trained over a period of several months to use an EEG-based brain-computer
      interface (BCI) for verbal communication. The patient learned to "produce" two
      distinct EEG patterns by mental imagery and to use this skill for BCI-controlled
      spelling. The EEG feedback training was conducted at a clinic for Assisted
      Communications, supervised from a distant laboratory with the help of a
      telemonitoring system. As a function of training sessions significant learning
      progress was found, resulting in an average accuracy level of 70% correct
      responses for letter selection. At present, "copy spelling" can be performed with
      a rate of approximately one letter per minute. The proposed communication device,
      the "Virtual Keyboard", may improve actual levels of communication ability in
      completely paralyzed patients. "Telemonitoring-assisted" training facilitates
      clinical application in a larger number of patients.

PMID- 14677110
TI  - [Public statement of the German Society for Rehabilitation of the Disabled on the
      Federal Employment Agency's rehabilitation policies].

PMID- 14677111
TI  - [Prevention in children at risk of disablement to take precedence over costly
      early intervention, special schooling and rehabilitation].

PMID- 14677112
TI  - The immunobiology of natural killer cells and bone marrow allograft rejection.
AB  - Natural killer (NK) cells mediate the acute rejection of bone marrow cell (BMC)
      allografts, but not solid tissue grafts, in lethally irradiated mice. However,
      the mechanisms underlying this capability for rejecting BMC remain unclear. NK
      cells express (1) inhibitory receptors specific for major histocompatibility
      complex (MHC) class I molecules and (2) activating receptors with diverse
      specificities. Inhibitory NK receptors confer to NK cells the ability to
      discriminate between MHC class I-positive and -negative target cells and are
      therefore involved in the control of NK cell tolerance to self, as well as in the
      elimination of cells that have downregulation of MHC class I molecules.
      Preclinical studies in mice have provided good evidence that subsets of NK cells
      that bear different combinations of both inhibitory and activating Ly49 receptors
      can interact with each other and target specific BMC rejection, as well as NK
      cell responses toward tumor cells. Recent clinical studies have also shown that
      the use of killer cell immunoglobulin-like receptor ligand incompatibility in
      patients with leukemia who received hematopoietic stem cell transplants
      correlated not only with the elimination of graft rejection, but also with
      eradication of tumor and prevention of graft-versus-host disease; this offers a
      significant advantage for survival. In this review, we attempt to bring together
      literature regarding the biology of NK cells and discuss the current issues in
      bone marrow transplantation and the potential clinical role of NK cell
      alloreactivity in the efficacy of this procedure for immunotherapy of cancer and
      infectious states.

PMID- 14677113
TI  - Selective elimination of alloreactive donor T cells attenuates graft-versus-host
      disease and enhances T-cell reconstitution.
AB  - Impaired T-cell immune reconstitution is a major complication after allogeneic
      bone marrow transplantation (BMT) and is particularly exacerbated in the setting
      of graft-versus-host disease (GVHD). Conventional approaches to reduce GVHD, such
      as T-cell depletion or pharmacologic immunosuppression, typically fail to enhance
      T-cell immunity and often further exacerbate this problem. An alternative
      strategy to mitigate GVHD severity is the selective elimination of graft-versus
      host-reactive donor T cells by using an incorporated thymidine kinase suicide
      gene. This approach has been shown to effectively reduce GVHD, although the
      effect of this strategy on T-cell reconstitution is unresolved. We addressed this
      question in a murine BMT model (C57BL/6 [H-2(b)] --> AKR/J [H-2(k)]) in which
      donor and recipient differ at major and minor histocompatibility antigens.
      Lethally irradiated AKR recipients transplanted with T cell-depleted bone marrow
      plus thymidine kinase-positive T cells followed by post-BMT ganciclovir (GCV)
      administration had more prompt and complete normalization of the T-cell
      repertoire than phosphate-buffered saline-treated GVHD control animals. By 60
      days after transplantation, mice administered GCV had T-cell repertoires that
      were virtually indistinguishable from those of mice that underwent
      transplantation with T cell-depleted bone marrow alone (no GVHD controls) when
      assayed by T-cell receptor (TCR) spectratyping. In contrast, phosphate-buffered
      saline-treated animals had persistent skewing in most Vbeta families. T cells
      obtained from GCV-treated mice also had significantly higher in vitro
      proliferative responses after posttransplantation inoculation with ovalbumin than
      GVHD animals, indicating that CD4(+) T-cell responses against a nominal antigen
      were better preserved in these chimeras. Finally, GCV-treated mice had augmented
      immune reconstitution in response to exogenous interleukin-7 administration, as
      evidenced by increased overall spleen cellularity and absolute numbers of T and B
      cells. This was in contrast to GVHD control animals, which had a blunted response
      to interleukin-7 administration. These data indicate that GVHD severity can be
      significantly reduced by selective elimination of alloreactive donor T cells
      without compromise of T-cell immunity. Moreover, in light of previous studies
      demonstrating that this strategy can reduce GVHD without loss of alloengraftment
      and antileukemia reactivity, further examination of this approach in humans seems
      warranted.

PMID- 14677114
TI  - Reduced-intensity transplantation for patients with myelodysplastic syndrome
      achieves durable remission with less graft-versus-host disease.
AB  - Reduced-intensity allogeneic transplantations for myelodysplastic syndrome (MDS)
      patients have been limited by significant graft-versus-host disease (GVHD),
      treatment-related mortality, and disease relapse. We treated 18 MDS patients
      ineligible for standard allogeneic transplantation with a preparative regimen of
      photopheresis day -7 and -6, pentostatin 4 mg/m(2) by continuous infusion day -5
      and -4, and total body irradiation 600 cGy in 3 fractions day -3 and -2, followed
      by allogeneic stem cell infusion from 6/6 or 5/6 HLA-matched related donors or
      6/6 HLA-matched unrelated donors. GVHD prophylaxis consisted of cyclosporin A and
      a short course of methotrexate. The median age was 54 years (range, 30-70 years).
      Diagnoses included refractory anemia (n = 2), refractory anemia with ringed
      sideroblasts (n = 2), refractory anemia with excess blasts (n = 10), refractory
      anemia with excess blasts in transformation (n = 3), and chronic myelomonocytic
      leukemia (n = 1). Sixteen of 18 patients developed full donor chimerism with no
      day +100 transplant-related mortality. Grade II to IV acute GVHD and extensive
      chronic GVHD developed in 19% and 18% of patients, respectively. Disease relapse
      occurred in 2 patients. At a median follow-up of 14 months (range, 1-35 months),
      the 1-year failure-free and overall survival were 64% and 65%, respectively. Our
      photopheresis and pentostatin-based reduced-intensity preparative regimen for
      allogeneic bone marrow transplantation in high-risk MDS patients achieves
      successful donor engraftment and disease remission with less transplant toxicity
      and grade II to IV acute GVHD.

PMID- 14677115
TI  - Graft-versus-host disease of the vulva and/or vagina: diagnosis and treatment.
AB  - We describe a series of women after allogeneic stem cell transplantation with
      vaginal graft-versus-host disease (GVHD) who were treated with topical
      cyclosporine, surgery, or both. We reviewed the medical charts of 11 women who
      presented with vaginal pain, discomfort, and vaginal scarring (inability to
      perform a Papanicolaou test or have vaginal intercourse because of pain). Vaginal
      symptoms develop an average of 10 months from bone marrow transplantation.
      Symptoms and physical findings include excoriated and ulcerated mucosa, thickened
      mucosa, narrowed introitus, and obliterated introitus from dense scar tissue that
      does not resolve with systemic or topical estrogens. The severity of symptoms and
      the physical findings in our study population did not correlate with age, type of
      leukemia, type of transplant, or severity or acute or chronic GVHD. Excoriated
      mucosa and moderately thickened mucosa were successfully treated with topical
      cyclosporine. Extensive synechiae and complete obliteration of the vaginal canal
      required surgical lysis with postoperative topical cyclosporine. Vaginal GVHD can
      successfully be treated with topical cyclosporine when mild to moderate disease
      is present. Surgical lysis with topical cyclosporine is required when more severe
      disease ensues.

PMID- 14677116
TI  - A long-term follow-up report on allogeneic stem cell transplantation for patients
      with primary refractory acute myelogenous leukemia: impact of cytogenetic
      characteristics on transplantation outcome.
AB  - The prognosis of patients with primary refractory acute myelogenous leukemia
      (AML) is poor. Our initial report suggested that some patients could achieve
      durable remission after allogeneic stem cell transplantation (SCT). Herein, we
      update our initial experience and report further analysis of this group of
      patients to determine whether there are pre-SCT prognostic factors predictive of
      posttransplantation relapse and survival. We reviewed the records of 68 patients
      who consecutively underwent transplantation at the City of Hope Cancer Center
      with allogeneic SCT for primary refractory AML between July 1978 and August 2000.
      Potential factors associated with overall survival and disease-free survival were
      examined. With a median follow-up of 3 years, the 3-year cumulative probabilities
      of disease-free survival (DFS), overall survival (OS), and relapse rate for all
      68 patients were 31% (95% confidence interval [CI], 20%-42%), 30% (95% CI, 18%
      41%), and 51% (95% CI, 38%-65%), respectively. In multivariate analysis, the only
      variables associated with shortened OS and DFS included the use of an unrelated
      donor as the stem cell source (relative risk, 2.23 [OS] and 2.05 [DFS]; P =.0005
      and.0014, respectively) and unfavorable cytogenetics before SCT (relative risk:
      1.68 [OS] and 1.58 [DFS]; P =.0107 and.0038, respectively). Allogeneic SCT can
      cure approximately one third of patients with primary refractory AML. Cytogenetic
      characteristics before SCT correlate with transplantation outcome and
      posttransplantation relapse.

PMID- 14677117
TI  - Unrelated umbilical cord blood transplantation in adult patients.
AB  - Since January 1996, we have administered myeloablative therapy followed by
      infusion of unrelated umbilical cord blood cells in 57 adult patients with high
      risk disease. The median age was 31 years (range, 18-58 years), and the median
      weight was 70 kg (range, 46-110 kg). Two patients were treated for genetic
      disorders and 55 for advanced hematologic malignancies. The preparative regimens
      were total body irradiation or busulfan based, both with antithymocyte globulin.
      HLA matching between donor and recipient was 3 of 6 in 3 patients, 4 of 6 in 44
      patients, 5 of 6 in 8 patients, and 6 of 6 in 2 patients. The median nucleated
      cell dose was 1.50 x 10(7)/kg (range, 0.54-2.78 x 10(7)/kg), and the median
      CD34(+) cell dose was 1.37 x 10(5)/kg (range, 0.02-12.45 x 10(5)/kg). All
      patients received granulocyte colony-stimulating factor after transplantation
      until neutrophil recovery. Graft-versus-host disease prophylaxis consisted of
      cyclosporine and steroids. The median number of days to an absolute neutrophil
      count of 500/microL was 26 (range, 12-55 days). The median time to an
      untransfused platelet count of >20000/microL was 84 days (range, 35-167 days).
      Seventeen patients developed grade II to IV acute GVHD. The median survival of
      the entire group was 91 days (range, 10-2251 days). Eleven patients were alive at
      a median follow-up of 1670 days (range, 67-2251 days), 1 with autologous recovery
      and 1 with relapsed lymphoma. The actuarial projected 3-year survival is 19%.
      Infection was the primary cause of death. These results suggest that unrelated
      umbilical cord blood transplantation is a viable option for adult patients and
      should be explored in patients with earlier-stage disease.

PMID- 14677126
TI  - Rapid dissemination of two-photon excitation microscopy prompts new applications.

PMID- 14677118
TI  - Correlation between the numbers of naive T cells infused with blood stem cell
      allografts and the counts of naive T cells after transplantation.
AB  - Naive T cells after allogeneic hematopoietic cell transplantation are thought to
      originate from the engrafted hematopoietic cells. In this report, we show that
      there is a correlation between the number of naive CD4 T cells infused with
      peripheral blood stem cell grafts and the absolute number of peripheral naive CD4
      T cells on day 30 (R = 0.65; P <.001), day 80 (R = 0.63; P <.001), and day 180 (R
      = 0.66; P <.001) after transplantation. These results suggest that in the first 6
      months after transplantation, most naive CD4 T cells are derived from the naive T
      cells infused with the graft.

PMID- 14677127
TI  - Antecedents of two-photon excitation laser scanning microscopy.
AB  - In 1931, Maria Goppert-Mayer published her doctoral dissertation on the theory of
      two-photon quantum transitions (two-photon absorption and emission) in atoms.
      This report describes and analyzes the theoretical and experimental work on
      nonlinear optics, in particular two-photon excitation processes, that occurred
      between 1931 and the experimental implementation of two-photon excitation
      microscopy by the group of Webb in 1990. In addition to Maria Goppert-Mayer's
      theoretical work, the invention of the laser has a key role in the development of
      two-photon microscopy. Nonlinear effects were previously observed in different
      frequency domains (low-frequency electric and magnetic fields and magnetization),
      but the high electric field strength afforded by lasers was necessary to
      demonstrate many nonlinear effects in the optical frequency range. In 1978, the
      first high-resolution nonlinear microscope with depth resolution was described by
      the Oxford group. Sheppard and Kompfner published a study in Applied Optics
      describing microscopic imaging based on second-harmonic generation. In their
      report, they further proposed that other nonlinear optical effects, such as two
      photon fluorescence, could also be applied. However, the developments in the
      field of nonlinear optical stalled due to a lack of a suitable laser source. This
      obstacle was removed with the advent of femtosecond lasers in the 1980s. In 1990,
      the seminal study of Denk, Strickler, and Webb on two-photon laser scanning
      fluorescence microscopy was published in Science. Their paper clearly
      demonstrated the capability of two-photon excitation microscopy for biology, and
      it served to convince a wide audience of scientists of the potential capability
      of the technique.

PMID- 14677128
TI  - Notes on theory and experimental conditions behind two-photon excitation
      microscopy.
AB  - This report deals with the fundamental quantum physics behind two-photon
      excitation also providing a link to the experimental consequences exploited in
      microscopy. The optical sectioning effect is demonstrated as well as the
      distribution of excitation and of fluorescence emission.

PMID- 14677129
TI  - Practical limits of resolution in confocal and non-linear microscopy.
AB  - Calculated and measured resolution figures are presented for confocal microscopes
      with different pinhole sizes and for nonlinear (2-photon and second harmonic)
      microscopes. A modest degree of super-resolution is predicted for a confocal
      microscope but in practice this is not achievable and confocal fluorescence gives
      little resolution improvement over widefield. However, practical non-linear
      microscopes do approach their theoretical resolution and therefore show no
      resolution disadvantage relative to confocal microscopes in spite of the longer
      excitation wavelength.

PMID- 14677130
TI  - Novel diode-pumped infrared tunable laser system for multi-photon microscopy.
AB  - We report on a novel laser source, emitting high energy (20 nanoJoule)
      femtosecond pulses, in a broad spectrum (250 nm). This source is easily tuned
      from 950 to 1200 nm, without any laser adjustment, and delivers sub-300
      femtosecond pulses with a 10-nm spectral width.

PMID- 14677131
TI  - Ultracompact autocorrelator for multiphoton microscopy.
AB  - Pulse temporal characterization is a fundamental task when operating a
      Ti:Sapphire ultrafast laser system for multiphoton microscopy applications. In
      the present report, an ultracompact autocorrelator setup and a simple procedure
      is reported to perform pulse width measurements at the focal plane of the
      microscope objective without the need of any further instrumentation, aside from
      a few optical elements, since the confocal microscope, detection, data
      acquisition, processing, and displaying capabilities are used.

PMID- 14677132
TI  - Distance measurement by circular scanning of the excitation beam in the two
      photon microscope.
AB  - We developed a method to measure relative distances with nanometer accuracy of
      fluorescent particles of different color in a two-photon scanning fluorescence
      microscope, with two-channel photon counting detection. The method can be used in
      the 10-500 nm range, for distances below the resolution limit of standard far
      field microscopy. The proposed technique is more efficient than the methods using
      raster scanning. To achieve maximum sensitivity in the radial direction, the
      excitation beam is moved periodically in a circular orbit with a radius of the
      size of the point spread function. The phase and the modulation of the periodic
      fluorescence signal, calculated by fast Fourier transform, gives the phase and
      the radial distance of the particle from the center of scanning. The coordinates
      of particles are recovered simultaneously in the two channels and the relative
      distance is calculated in real time. Particles can be tracked by moving the
      center of scanning to the recovered position, while measuring the distance from
      the second particle. Intensity data are saved and fitted later by a model
      accounting for light leakage between the channels. The total number of detected
      photons limited the accuracy of the position and distance measurement.
      Experiments demonstrating the advantages of the method were performed on
      fluorescent spheres and single dye molecules immobilized on quartz surface.

PMID- 14677133
TI  - Probing microscopic diffusion by 2-photon flash photolysis: measurement of
      isotropic and anisotropic diffusion in lens fiber cells.
AB  - Two-photon excited flash photolysis (TPEFP) was used to photorelease caged
      fluorescein in test solutions and inside fiber cells of the eye lens. Accurate
      alignment between the focus of the IR beam and the probe beam from the confocal
      microscope was achieved with an accessory focussing lens and computer models of
      diffusion were fit to experimental data to extract apparent diffusion
      coefficients. Inside a fiber cell, the diffusion coefficient for fluorescein was
      4 x 10(-7) cm(2)/s at 21 degrees C, a value an order of magnitude lower than
      observed in free solution. Fluorescence also diffused between fiber cells via gap
      junctions. In the periphery, diffusion between cells occurred mainly in a radial
      direction while deep in the lens the diffusion between cells appeared more
      isotropic. Diffusion between cells was slower than inside cells and corresponded
      to less than approximately 1% of the area between cells being available for
      diffusion. This value is in good agreement with that expected from measurements
      of gap junction structure and packing density if a 1-1.5-nm aqueous gap junction
      pore is nearly always open.

PMID- 14677134
TI  - Fluorescence lifetime imaging by time-correlated single-photon counting.
AB  - We present a time-correlated single photon counting (TCPSC) technique that allows
      time-resolved multi-wavelength imaging in conjunction with a laser scanning
      microscope and a pulsed excitation source. The technique is based on a four
      dimensional histogramming process that records the photon density over the time
      of the fluorescence decay, the x-y coordinates of the scanning area, and the
      wavelength. The histogramming process avoids any time gating or wavelength
      scanning and, therefore, yields a near-perfect counting efficiency. The time
      resolution is limited only by the transit time spread of the detector. The
      technique can be used with almost any confocal or two-photon laser scanning
      microscope and works at any scanning rate. We demonstrate the application to
      samples stained with several dyes and to CFP-YFP FRET.

PMID- 14677135
TI  - Live cell ultraviolet microscopy: a comparison between two- and three-photon
      excitation.
AB  - We compare conventional infrared laser based three-photon excitation with a
      visible laser based two-photon excitation scheme for imaging the ultraviolet
      fluorophore serotonin in solution and in live cells. To obtain a signal level of
      1000 photons per second per mM serotonin solution, we need a back aperture power
      of 5 mW at 550 nm (for two-photon excitation) and 33 mW at 740 nm (for three
      photon excitation). The detectivity of serotonin (defined as the concentration of
      serotonin that yields a signal equivalent to three times the standard deviation
      of the signal obtained from the buffer alone) is 12 microM for two-photon, and
      220 microM for three-photon excitation. Surprisingly, for live cell imaging of
      vesicular serotonin in serotonergic cells, three-photon excitation appears to
      provide better image contrast than two-photon excitation. The origin of this is
      traced to the concentration-dependent shift of the serotonin emission spectrum.

PMID- 14677136
TI  - Characterization of two-photon excitation fluorescence lifetime imaging
      microscopy for protein localization.
AB  - Two-photon excitation fluorescence resonance energy transfer (2P-FRET) imaging
      microscopy can provide details of specific protein molecule interactions inside
      living cells. Fluorophore molecules used for 2P-FRET imaging have characteristic
      absorption and emission spectra that introduce spectral cross-talk (bleed
      through) in the FRET signal that should be removed in the 2P-FRET images, to
      establish that FRET has actually occurred and to have a basis for distance
      estimations. These contaminations in the FRET signal can be corrected using a
      mathematical algorithm to extract the true FRET signal. Another approach is 2P
      FRET fluorescence lifetime imaging (FLIM). This methodology allows studying the
      dynamic behavior of protein-protein interactions in living cells and tissues. 2P
      FRET-FLIM was used to study the dimerization of the CAATT/enhancer binding
      protein alpha (C/EBPalpha). Results show that the reduction in donor lifetime in
      the presence of acceptor reveals the dimerization of the protein molecules and
      also determines more precisely the distance between the donor and acceptor. We
      describe the development and characterization of the 2P-FRET-FLIM imaging system
      with the Bio-Rad Radiance2100 confocal/multiphoton microscopy system.

PMID- 14677137
TI  - Performances of high numerical aperture water and oil immersion objective in deep
      tissue, multi-photon microscopic imaging of excised human skin.
AB  - Multi-photon fluorescence microscopy (MPFM) is a powerful technique for imaging
      scattering, biological specimens in depth. In addition to the sectioning effect
      generated by the point-like excitation volume, the near-infrared wavelengths used
      for multi-photon excitation allow deeper penetration into optically turbid
      specimens. In physiological specimens, the optical properties such as the
      scattering coefficients and refractive indices are often heterogeneous. In these
      specimens, it is not clear which type of immersion objective can provide
      optimized images in-depth. In particular, in-depth dermatological imaging
      applications using MPFM requires such optimization to obtain qualitative and
      quantitative information from the skin specimens. In this work, we address this
      issue by comparing the performances of two common types of high numerical
      aperture (NA) objectives: water-immersion and oil-immersion. A high-quality water
      immersion objective (Zeiss, 40 x C-Apochromat, NA 1.2) and a comparable oil
      immersion objective (Zeiss, 40 x Fluar, NA 1.25) were used for in-depth imaging
      of autofuorescent excised human skin and sulforhodamine B treated human skin
      specimens. Our results show that in the epidermal layers, the two types of
      immersion objectives perform comparably. However, in the dermis, multi-photon
      imaging using the oil immersion objective results in stronger fluorescence
      detection. These observations are most likely due to the degraded point-spread
      function (PSF) caused by refractive index mismatch between the epidermis and the
      dermis.

PMID- 14677138
TI  - APOE is associated with age-of-onset, but not cognitive functioning, in late-life
      depression.
AB  - OBJECTIVE: There is a recognized but poorly understood relationship between late
      life depression (LLD) and progressive dementia. Both cognitive impairment co
      occurring with LLD and a late age-of-onset of first lifetime depressive episode
      appear to be associated with subsequent progressive dementia. A history of major
      depression, especially when the first onset occurs in late-life, has been
      identified as a risk factor for Alzheimer's disease (AD). The major genetic risk
      factor for sporadic AD is carrying one or more apolipoprotein E4 (APOE4) alleles.
      We hypothesized that the association between LLD and dementia risk would be
      mediated by APOE4, specifically that APOE4 allele frequency would be associated
      with cognitive impairment and later age-of-depression-onset. We also predicted
      that APOE4 allele frequency would be increased among subjects with LLD. METHODS:
      We compared the distribution of APOE2, APOE3, and APOE4 alleles in groups of LLD
      (n=160), AD (n=568) and elderly control (EC; n=156) subjects. RESULTS: The allele
      distribution of the cognitively impaired LLD subgroup was not different from
      either the cognitively normal subgroup or the EC group but was different from the
      AD group. However, mean age-of-onset of depression in APOE4 carriers (51.4+/
      20.7) was significantly lower than non-carriers (58.8+/-16.8). The allele
      distribution in LLD overall was significantly different from the AD but not the
      EC group. CONCLUSIONS: The finding that neither LLD, accompanying cognitive
      impairment, nor late age-of-onset was associated with an increased APOE4 allele
      frequency suggests that LLD acts as a risk factor for developing AD as well as
      non-AD dementia through mechanisms independent of APOE4. The unexpected finding
      that age-of-onset of LLD was significantly reduced in APOE4 carriers is similar
      to the association between APOE4 and age-of-onset in AD. Replication of the
      association of APOE4 with earlier age-of-depression-onset is indicated.

PMID- 14677139
TI  - Gender in elderly suicide: analysis of coroners inquests of 200 cases of elderly
      suicide in Cheshire 1989-2001.
AB  - OBJECTIVES: The aim of this study is to review gender differences in elderly
      suicide in relation to specific social aspects of the suicidal process and health
      care contact before death. Such information may have practical value in
      identifying and targeting vulnerable elderly in whom suicide may be potentially
      preventable. METHODS: Data were extracted from the records of coroner's inquests
      into all reported suicide of persons aged 60 and over, in Cheshire over a period
      of 13 years 1989-2001. The Coroner's office covers the whole county of Cheshire
      (population 1 000 000). RESULTS: Men were less likely to have been known to
      psychiatric services (Odds Ratio [OR] 0.4 95% 0.2-0.6) and with less frequently
      reported history of previous attempted suicide compared to women (OR 0.5 95%
      Confidence Intervals [CI] 0.2-1). All deceased from ethnic minorities were men,
      none of whom had been known to psychiatric services. There was no significant
      difference between women and men in relation to, physical or psychiatric
      morbidity, GP contact prior to suicide, intimation of intent or living alone. Of
      suicide victims not known to services a surprisingly high proportion of 38% and
      16% were found to have psychiatric morbidity in men and women respectively.
      CONCLUSION: Suicide is an important problem in the elderly with gender playing an
      important part in their social behaviour but a high proportion of the deceased
      were not known to local services. Primary Care professionals have an important
      role to play in reducing elderly suicide as most contact with the health service
      in elderly suicide seem to be with GPs.

PMID- 14677140
TI  - Effects of reminiscence and life review on late-life depression: a meta-analysis.
AB  - AIM: To assess the effectiveness of reminiscence and life review on late-life
      depression across different target groups and treatment modalities. METHOD:
      Twenty controlled outcome studies were retrieved from Psychlit, Medline and
      Dissertation Abstracts. For each study a standardised effect size, d, was
      calculated and a random-effects meta-analysis was conducted. RESULTS: An overall
      effect size of 0.84 (95% Confidence Intervals (CI)=0.31-1.37) was found,
      indicating a statistically and clinically significant effect of reminiscence and
      life review on depressive symptomatology in elderly people. This effect is
      comparable to the effects commonly found for pharmacotherapy and psychological
      treatments. The effect was larger in subjects with elevated depressive
      symptomatology (d=1.23) as compared to other subjects (d=0.37). Other
      characteristics of the subjects or interventions were not found to be related to
      increased or decreased effect sizes. DISCUSSION: Reminiscence and life review are
      potentially effective treatments for depressive symptoms in the elderly and may
      thus offer a valuable alternative to psychotherapy or pharmacotherapy. Especially
      in non-institutionalised elderly people-who often have untreated depression-it
      may prove to be an effective, safe and acceptable form of treatment. Randomized
      trials with sufficient statistical power are necessary to confirm the results of
      this study.

PMID- 14677141
TI  - Nursing home suicides-a psychological autopsy study.
AB  - OBJECTIVE: Older adults comprise a fifth of all suicides. Elders are the fastest
      growing part of the population, thus the number of persons needing nursing home
      care will increase dramatically in the near future. Little information has been
      available about suicides in nursing homes. The present study described all
      suicides among older adults in nursing homes in Finland during a 12-month period
      emphasizing the factors that have been found to be associated with suicide in the
      general elderly population. METHODS: Drawing on data from a psychological autopsy
      study of all suicides (n=1397) in Finland during one year, all suicides committed
      by patients in nursing homes were identified. Retrospective DSM-IV consensus
      diagnoses were assigned. RESULTS: Twelve elderly (aged 60 years or more) nursing
      home residents who died by suicide, 0.9% of all suicides, were identified. The
      primary finding of the present study was that nursing home residents who died by
      suicide had suffered from highly comorbid somatopsychiatric disorders. One or
      more diagnoses on Axis I were made for all who died by suicide in nursing home.
      Depressive syndrome was diagnosed in three-quarters of subjects. Only a third of
      these were identified to have suffered from depressive symptoms before their
      death. CONCLUSIONS: Early recognition and adequate treatment of both somatic
      diseases and mental disorders, particularly depression, as well as early
      recognition of suicide risk among nursing home residents, are needed in order to
      prevent suicide.

PMID- 14677142
TI  - Modelling late-life depression.
AB  - OBJECTIVE: To determine if we could find support for a three-class depression sub
      typing model (and identify differentiating constituent clinical features) in a
      sample of elderly depressed patients. BACKGROUND: Depression is currently
      modelled dimensionally, with little concession to descriptive psychopathology and
      distinction of meaningful clinical depressive sub-types. We have proposed a three
      class hierarchical specificity model for sub-typing the depressive disorders
      (comprising psychotic, melancholic and non-melancholic depression), with
      specificity referring to two clinical features (psychotic symptoms and
      psychomotor disturbance or PMD) separating the first two classes from a residual
      non-melancholic class. METHOD: Subjects were aged 65 years or more, non-demented
      and being treated for depression. Extensive clinical assessment was undertaken,
      while several standardised measures were administered. 'Bottom up' analyses were
      data driven, while 'top down' analyses respected DSM-III-R decision rules.
      Dimensional and categorical multivariate analyses sought to identify features
      differentiating psychotic depression (PD), melancholic depression (MEL) and a
      residual non-melancholic (NON-MEL) class. RESULTS: Of the 123 referred patients
      (having a mean age of 75.6 years), 46 had DSM-defined PD, 46 had MEL and 31 were
      assigned as NON-MEL. Mean total CORE scores (measuring PMD) more clearly
      distinguished the groups than scores on two depression severity measures.
      Psychotic depression was best distinguished from melancholic depression by
      psychotic features, as well as more severe PMD and anhedonia. Melancholic
      depression was best distinguished from non-melancholic depression by PMD,
      terminal insomnia and pathological guilt. CONCLUSION: The specificity of PMD to
      the definition of the psychotic and melancholic depression was confirmed in our
      elderly depressed sample. Clinical features identified as distinguishing
      psychotic, melancholic and non-melancholic depression were broadly consistent
      with findings from our previous studies involving younger subjects and with our
      three-class hierarchical model.

PMID- 14677143
TI  - Alzheimer's disease: usefulness of the Family Strain Questionnaire and the Screen
      for Caregiver Burden in the study of caregiving-related problems.
AB  - OBJECTIVES: The economic and psychosocial impacts of Alzheimer's disease (AD) on
      caregivers are so well documented that they have stimulated socioeconomic
      regulations that are international in scope. In Italy caregivers have the right
      to receive economic and psychosocial aid. However, to distribute such aid the
      needs of caregivers, must be properly assessed. Here we have attempted to
      integrate two measures, the Family Strain Questionnaire (FSQ) and the Screen for
      Caregiver Burden (SCB), in order to evaluate caregiver needs that are both
      general and specific to AD. MATERIAL AND METHODS: The SCB and FSQ were
      administered to 91 primary caregivers of home-based patients with AD. Caregivers
      also were asked to rate the activities of daily living of their care recipients,
      the latter of which were administered the Mini-Mental State Examination. RESULTS:
      The SCB and FSQ provide different, but complementary assessments of the needs of
      AD caregivers. The SCB identifies situations that are potentially stressful to AD
      caregivers and the FSQ identifies the needs of specific caregivers (e.g. men vs
      women, spouses vs children, unemployed vs employed). CONCLUSION: Together these
      measures may help government agencies to assess caregiver needs beyond those
      assessed by each individual measure.

PMID- 14677144
TI  - A longitudinal study of neuropsychological change in individuals with Parkinson's
      disease.
AB  - OBJECTIVES: Neuropsychological changes in individuals with Parkinson's disease
      (PD) were studied longitudinally. METHODS: Sixty-nine idiopathic PD patients,
      with Mini-Mental State Examination (MMSE) scores falling within normal range, and
      37 elderly control participants were given neuropsychological tests twice
      approximately two years apart. RESULTS: The PD group performed poorer than the
      control group on Semantic Fluency, Letter Fluency, Modified Wisconsin Card
      Sorting Task, and Block Design at test time 1. Two years later, the PD group
      showed significant decline in Semantic and Letter Fluency. A subset of 12 PD
      patients declined in mental status by second testing (>4 MMSE points). Cox
      proportional-hazards models were used to see if any baseline measures were
      associated with relative risk of decline in mental status. In the final model,
      Repetition performance and Age were significantly associated with cognitive
      decline. CONCLUSIONS: Consistent with previous studies, executive function tasks
      were those most susceptible to disease progression.

PMID- 14677145
TI  - A systematic review of cognitive decline in the general elderly population.
AB  - BACKGROUND: The public health impact of cognitive decline and dementia is
      increasing as the population ages. Studies exploring therapies or risk factors
      for cognitive impairment require understanding of expected age-related decline.
      OBJECTIVE: To establish the rate of age-related cognitive decline in the general
      elderly population. DESIGN: Systematic review of studies of cognitive decline in
      the general elderly population. Medline, Embase and PsycINFO databases were
      searched using an adapted version of McMaster's aetiology, causation and harm
      strategies and the Cochrane Dementia and Cognitive Impairment Group strategy.
      Grey literature was explored and experts contacted. A second observer was
      involved at all stages and quality appraisal of included studies was performed.
      Included studies were representative, community-based, cohort studies of people
      aged over 60, incorporating individuals with dementia. RESULTS: Identification of
      5990 abstracts and retrieval of 163 full texts led to inclusion of 19 papers.
      Heterogeneity made narrative review the appropriate method of data synthesis.
      Some degree of cognitive impairment with increasing age was found in all studies,
      although the extent varied. The prevalence of cognitive impairment and the rate
      of decline increased with age. Studies were of variable quality. CONCLUSIONS:
      Cognitive decline is almost universal in the general elderly population and
      increases with age. Improved communication between researchers and between
      clinicians to identify a core minimum data set of neuropsychological tests that
      could be used in different populations would support consistent study design and
      meta-analysis, helping to quantify the true rate of cognitive decline in the
      elderly and assisting diagnosis in clinical practice.

PMID- 14677146
TI  - Use of psychotropics among home-dwelling nondemented and demented elderly.
AB  - OBJECTIVE: To describe the use of psychotropics in the nondemented and demented
      elderly. PARTICIPANTS: The home-dwelling elderly (n=523) among the random sample
      of 700 subjects from the total population of individuals aged 75 years or more in
      1998 and living in the city of Kuopio, Finland. METHODS: A trained nurse
      interviewed the participants about their health and current use of medicines. A
      geriatrician performed clinical examinations and diagnosed diseases. Dementia and
      depression were diagnosed according to the DSM-IV criteria. RESULTS: The demented
      subjects used more medicines of all kinds (p<0.01), and especially more
      psychotropics than the nondemented (p<0.001). One in four demented subjects,
      compared to one in ten nondemented ones used at least two psychotropics (p<0.01).
      The demented subjects used antipsychotics six times more often than the
      nondemented ones (p<0.001). Among the nondemented subjects, one out of two
      antipsychotics users was suffering from depression according to DSM-IV criteria.
      Three out of four persons who had dementia with Lewy bodies were using
      psychotropics. Persons with moderate dementia were more commonly using all kinds
      of psychotropic preparations especially, antipsychotics three times more commonly
      than persons with mild or severe dementia. CONCLUSION: Psychotropics, especially
      antipsychotics, are commonly used in the treatment of both nondemented and
      demented elderly, even without proper indication. Physicians need more training
      about the appropriate use of psychotropics to minimize their adverse effects.

PMID- 14677147
TI  - The association of psychosocial factors and depression with hypertension among
      older adults.
AB  - OBJECTIVE: To examine the relationship between depression and hypertension in an
      elderly population and how psychosocial variables influence this relationship.
      METHODS: The study included 293 subjects, who met DSM-IV criteria for unipolar
      depression, and 151 subjects with no psychiatric disorder. All subjects were over
      the age of 58. Participants were administered the Duke Depression Evaluation
      Schedule at baseline and at yearly intervals for 3 years. RESULTS: Cross
      sectional analyses of baseline data showed that hypertensive patients were more
      likely to be depressed and of non-white race. Bivariate analyses provided
      evidence that hypertension was associated with higher amounts of total stressors
      and lower social support. No differences in the prevalence of hypertension were
      found between men and women. In addition, there was no evidence of change in
      hypertension status over time. CONCLUSION: Patients, especially minorities, who
      experience depression, stress, or a lack of social support, are at an increased
      likelihood of having hypertension and clinicians should consider this risk when
      treating this population.

PMID- 14677148
TI  - Novel 3,3a,4,5,6,7-hexahydroindazole and arylthiazolylpyrazoline derivatives as
      anti-inflammatory agents.
AB  - A novel series of 7-benzylidene-3, 3a, 4, 5, 6, 7-hexahydro-3-phenyl-2H-indazole
      substituted at the 2-position were synthesized. The reaction of 2, 6-bis
      benzylidenecyclohexanone (1) with thiosemicarbazide in the presence of NaOH
      afforded a mixture of the 3-H, 3a-H trans 2 and cis 2a diastereoisomers which
      have been separated by fractional recrystallization. Interaction of the first
      intermediate 2 with substituted phenacyl bromides, aromatic aldehydes and
      chloroacetic acid in presence of a mixture of acetic acid and acetic anhydride,
      and 2, 3-dichloroquinoxaline yielded the corresponding 7-benzylidene-3, 3a, 4, 5,
      6, 7-hexahydro-3-phenyl-2H-indazole derivatives substituted at the 2-position
      with 4-aryl-2-thiazolyl 3a, b, 5-arylidene-4, 5-dihydro-4-oxo-2-thiazolyl 4a, b
      and thiazolo[4, 5-b]quinoxalin-2-yl 5, respectively. Moreover, the other
      intermediates 3, 5-diaryl-1-thiocarbamoyl-2-pyrazolines 7a-d were reacted with
      the previously-mentioned reagents and gave the corresponding 3, 5-diaryl-1-(4
      aryl-2-thiazolyl)-2-pyrazolines 8a-h, 3, 5-diaryl-1-(5-arylidene-4, 5-dihydro-4
      oxo-2-thiazolyl)-2-pyrazolines 9a-d and 3, 5-diaryl-1-(thiazolo[4, 5-b]quinoxalin
      2-yl)-2-pyrazoline derivatives 10a, b, respectively. Some of the newly prepared
      compounds were subjected to evaluation for their anti-inflammatory activity. The
      structures of the new compounds were confirmed by elemental analyses as well as
      (1)H-NMR, IR, and MS data.

PMID- 14677149
TI  - Synthesis and in vitro antibacterial evaluation of novel imidazo[2',1':5,1]-1,2,4
      triazolo[4,3-c]-quinazoline derivatives of 5-thioxo-1, 2, 4-triazole, 4
      oxothiazolidine, and their open-chain counterparts.
AB  - Two novel series of imidazo[2', 1':5, 1]-1, 2, 4-triazolo[4, 3-c]quinazolines
      bearing 5-thioxo-1, 2, 4-triazoles, 6a-f, and 4-oxothiazolidines, 7a-f, were
      synthesized from corresponding thiosemicarbazide derivatives, 5a-f. The stepwise
      methodology applied to the preparation of compounds 5a-f was initiated with
      reaction of the parent 3-amino-1, 2, 4-triazolo[4, 3-c]quinazolines, 2, with
      ethyl 2-chloroacetoacetate resulting in annelation of the imidazole ring to give
      esters, 3a-c. However, hydrazinolysis of these ester derivatives gave the
      corresponding acid hydrazides, 4a-c, which on reaction with the appropriate alkyl
      isothiocyanate yielded compounds 5a-f. In turn, compounds 5, were cyclized with
      potassium hydroxide or with ethyl bromoacetate to give the corresponding
      thioxotriazoles 6 and oxothiazolidines 7, respectively. All synthesized compounds
      were screened for their in vitro antibacterial activity against various Gram
      positive and Gram-negative bacteria. Some test compounds were found to possess
      potent antibacterial activities. Compound, 7f, exhibited much higher potency than
      the reference standard ciprofloxacin, against both types of bacteria,
      particularly, Gram-positive organisms.

PMID- 14677150
TI  - Synthesis and antibacterial activity of 1beta-methyl-2-(5-substituted oxadiazolo
      pyrrolidin-3-yl-thio)carbapenem derivatives.
AB  - Synthesis of a new series of 1beta-methylcarbapenems with a substituted
      oxadiazolopyrrolidine 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 oxadiazole ring investigated. In particular,
      compounds 13a and 13c with ester and carbamoyl substituted oxadiazole moieties
      showed the most potent antibacterial activity.

PMID- 14677151
TI  - 1, 2-dihydroisoquinoline-N-acetic acid derivatives as new carriers for specific
      brain delivery I: synthesis and estimation of oxidation kinetics using
      multivariate calibration method.
AB  - In order to overcome the slow oxidation of 1, 2-dihydro-N-alkylisoquinoline, 1, 2
      dihydroisoquinoline-N-acetic acid derivatives (3b-d) were designed and
      synthesized as new chemical delivery systems (CDS) for the brain. Molecular
      orbital calculations for the suggested derivatives revealed that these carriers
      are stable against oxidation. However, hydrolysis to their corresponding anions
      will accelerate the rate of oxidation, and accordingly increase the efficiency of
      brain specific delivery. A multivariate calibration method for in vitro
      determination of the oxidation rate for the suggested brain specific chemical
      delivery system is described. The method is based on measurement of individual
      rates of oxidation of prepared 1, 2-dihydroisoquinolines, using silver ions to
      provide the corresponding quaternary forms. Components of binary mixtures formed
      through the oxidation step (composed of the dihydro-compound and its quaternary
      form), showed a considerable degree of spectral overlapping - more than 90% in
      all cases. Resolution of these binary mixtures under investigation has been
      accomplished mainly using classical least squares analysis. Kinetic oxidation
      data of the tested compounds revealed that these new CDSs have a reasonable
      oxidation rate for efficient brain delivery.

PMID- 14677152
TI  - Preparation of fluorescent nonpeptidic neuropeptide Y receptor ligands: analogues
      of the quinazoline-type anti-obesity Y5 antagonist CGP 71683A.
AB  - As part of a programme to develop fluorescence-based methods for the study of the
      interactions between G-protein coupled receptors (GPCRs) and their ligands the
      preparation of low molecular weight fluorescence-labelled neuropeptide Y (NPY)
      Y(5) antagonists is reported. The naphthylsulfonyl group in the potent
      quinazoline-type NPY Y(5) receptor antagonist CGP 71683A was replaced with a
      dansyl, nitrobenzoxadiazole (NBD) or acridine-9-carbonyl group. In radioligand
      binding studies on human Y(5) receptor expressing HEC-1B cells the substances
      labelled with acridine (K(i) 311 nM) and NBD (K(i) > 1000 nM) proved to be
      moderately active or inactive, respectively. By contrast, a K(i) value of 49 nM
      was found for the dansyl analogue compared to 2 nM for CGP 71683A. No binding to
      Y(1) receptors (SK-N-MC cells, displacement of [(3)H]propionyl-NPY) was detected
      for the new compounds at concentrations </= 1 microM.

PMID- 14677153
TI  - New antithrombotic 1-phthalazinamines with serotonin antagonistic properties.
AB  - We report nineteen 4-aryl- and 4-arylalkyl-1-phthalazinamines (5-8) which we
      prepared and tested for antithrombotic properties. All compounds were assayed for
      their antiplatelet activity in the "Born test" with collagen as inducer of the
      aggregation. N-[4-(1H-1, 2, 4-triazol-1-yl)butyl]-4-phenyl-1-phthalazin-amine (7
      c) was the most potent compound, having an IC(50) of 8 microM. When 5-HT
      (Serotonin) was used to start aggregation the N-(furan-2-yl-methyl)-4-phenyl-1
      pthtalazinamine (8 a) had an IC(50) of 2 microM. In vivo potencies were highly
      significant. N-[5-(1H-1, 2, 4-triazol-1-yl)pentyl]-4-phenyl-1-phthalazinamine (7
      d) inhibited thrombus formation by 12% (P < 0.002) in arterioles and 7% (P <
      0.01) in venoles as tested with our laser thrombosis model. For compound 8 a we
      surprisingly found an antagonism to the 5HT(2A) receptor, which is most likely
      the mechanism of the inhibition of aggregation by this compound.

PMID- 14677154
TI  - Evaluation of myocardial perfusion and left ventricular function six months after
      percutaneous transmyocardial laser revascularization: comparison of two Ho-YAG
      laser systems with the same wavelength, but different energy delivery and
      navigation systems.
AB  - BACKGROUND AND OBJECTIVES: Myocardial perfusion and left ventricular function
      (LVF) were assessed after percutaneous transmyocardial laser revascularization
      (PTMR) in patients not amenable to conventional revascularization, with a
      comparison of two laser systems. STUDY DESIGN/MATERIALS AND METHODS: PTMR was
      performed with an Eclipse laser in 15 patients, and with a Biosense DMR in 10
      patients. (201)Thallium scintigraphy, coronary angiography, and ventriculography
      were performed at baseline and at the 7.5+/-4.3-month follow-up. All patients in
      the Biosense DMR group and 10 in the Eclipse group underwent NOGA mapping before
      PTMR and after follow-up. RESULTS: The event-free survival rates were comparable,
      and the angina scores of all patients improved significantly, but more so in the
      Biosense DMR group than in the Eclipse group (1.2+/-1.1 vs. 2.3+/-0.9, P < 0.05).
      Both, the electrical activity assessed by NOGA mapping and the normalized
      (201)thallium uptake at redistribution improved significantly in the treated
      segments after Biosense DMR, while the global LVF decreased insignificantly in
      the Eclipse group. CONCLUSIONS: PTMR resulted in significant improvements in the
      clinical symptoms, but the electrical activity improved only in the Biosense DMR
      group, without transforming to a better LVF.

PMID- 14677155
TI  - Treatment of resistant port wine stains with the V Beam pulsed dye laser.
AB  - BACKGROUND AND OBJECTIVES: Pulsed dye lasers (PDL; 585 nm, 0.45 millisecond) are
      the treatment of choice for port wine stains (PWS). However, clearance rates vary
      widely and are in many patients incomplete. The objective of this prospective
      pilot study was to investigate the effects of a long pulse-duration 595 nm PDL (V
      Beam, Candela Laser Corporation, Wayland, MA) on previously treated PWS to
      ascertain whether further lightening can be obtained. Treatment response was
      assessed subjectively (photographs) and objectively with noninvasive techniques
      (reflectance spectrophotometer and spectrophotometric intracutaneous analysis
      scope (SIAscope)). STUDY DESIGN/MATERIALS AND METHODS: Twelve adult patients with
      congenital PWS each had four test patches with different spot sizes, fluences,
      and pulse widths carried out. The test area with the best response was selected
      and two laser treatments were performed at weeks 8 and 16. Photographs and
      measurements with a reflectance spectrophotometer and SIAscope (Astron Clinica,
      Cambridge, UK) were performed at baseline, before each treatment and at final
      review at week 24. RESULTS: Of the nine patients who completed the study three
      patients showed a good response (51-75% lightening), which was supported by
      measurements with the reflectance spectrophotometer and the SIAscope. A further
      three patients had fair improvement (26-50% lightening) and three patients had a
      minor or no response (0-25% lightening). In two patients a discrepancy between
      the degree of clinical response and some of the objective measurements was
      noticed. CONCLUSIONS: The 595 nm V Beam PDL appears to achieve further lightening
      of therapy-resistant PWS in the majority of patients (67%). Both reflectance
      spectrophotometer and SIAscope appear to permit assessment of objective treatment
      responses. Results require confirmation in larger studies.

PMID- 14677156
TI  - Influence of wavelength on response to laser photothermolysis of blood vessels:
      implications for port wine stain laser therapy.
AB  - BACKGROUND AND OBJECTIVE: Treatment of port wine stains (PWS) by photothermolysis
      can be improved by optimizing laser parameters. We have studied the all-important
      role of wavelength (lambda) by performing pulsed laser photothermolysis in the
      vasculature of the chick chorioallantoic membrane (CAM) assay. STUDY
      DESIGN/MATERIALS AND METHODS: The CAM contains an extensive microvascular network
      ranging from capillaries with diameter D < 20 microm to blood vessels of D
      approximately 120 microm. The CAM assay enables observation and real-time video
      documentation of blood flow in pre-capillary arterioles (A) and post-capillary
      venules (V). The ScleroPlus trade mark laser (Candela Corp., Wayland, MA) has a
      smooth output over its fixed 1.5 ms pulse duration and allows the operator to
      vary several treatment parameters such as wavelength, spot size, and energy.
      Blood vessels in the CAM were irradiated at two clinically relevant wavelengths,
      lambda = 587 or 597 nm, constant spot size (7 mm), and at different exposures (E
      = 5-12 J/cm(2)). Threshold exposure (E(th)) (at which non-reversible damage
      occurred) were 5 J/cm(2) at 587 nm and 8 J/cm(2) at 597 nm. Mathematical modeling
      was developed to interpret initial (within 30 seconds) injury of arterioles and
      venules at both wavelengths as a function of D when varying E. RESULTS: Vessel
      injury was graded off-line from videotapes. For all combinations of lambda and E,
      measurable injury was evident within 30 seconds of irradiation and maximal damage
      was reached in less than 10 minutes. Vessel damage was found to depend strongly
      on lambda. Damage decreased with increasing vessel size. For all D, damage of
      arterioles was greater than for corresponding venules. CONCLUSIONS: Selection of
      the correct wavelength is crucial for successful laser therapy of hypervascular
      lesions and, ideally, should be based on knowledge of vessel diameters for a
      specific PWS lesion and of optical penetration depths in blood. As a general
      statement, smaller blood vessels (D = 10-60 microm) should be treated using
      shorter wavelengths such as 585 nm. To ensure deposition of sufficient laser
      energy, irradiation at 585 nm, characterized by lower optical penetration depth
      in blood, may be preferable for PWS therapy.

PMID- 14677157
TI  - A pilot study of ICG laser therapy of acne vulgaris: photodynamic and
      photothermolysis treatment.
AB  - BACKGROUND AND OBJECTIVES: The near-infrared (NIR) laser radiation due to its
      high penetration depth is widely used in phototherapy. In application to skin
      appendages, a high selectivity of laser treatment is needed to prevent light
      action on surrounding tissues. Indocyanine green (ICG) dye may provide a high
      selectivity of treatment due to effective ICG uploading by a target and its
      narrow band of considerable absorption just at the wavelength of the NIR diode
      laser. The goal of this study is to demonstrate the efficacy of the NIR diode
      laser phototherapy in combination with topical application of ICG suggested for
      soft and thermal treatment of acne vulgaris. STUDY DESIGN/MATERIALS AND METHODS:
      Twenty-two volunteers with facile or back-located acne were enrolled. Skin sites
      of subjects were stained by ICG and irradiated by NIR laser-diode light (803 or
      809 nm). One mg/ml solution of ICG was applied for 5 or 15 minutes to the cleaned
      skin site. Untreated, only stained and only light irradiated skin areas served as
      controls. For soft acne treatment, the low-intensity (803 nm, 10-50 mW/cm(2), 5
      10 minutes) or the medium-intensity (809 nm, 150-190 mW/cm(2), 15 minutes)
      protocols were used. The single and multiple (up to 8-9) treatments were
      provided. The individual acne lesions were photothermally treated at 18 W/cm(2)
      (803 nm, 0.5 seconds) without skin surface cooling or at 200 W/cm(2) (809 nm, 0.5
      seconds) with cooling. RESULTS: The observations during 1-2 months showed that
      soft acne treatment decreased the number of active elements, reduced erythema and
      inflammation, and considerably improved the skin state without any side effects.
      At high power densities (up to 200 W/cm(2)), ICG stained acne inflammatory
      elements were destroyed for light exposures of 0.5 seconds. CONCLUSIONS: Based on
      the concept that hair follicle, especially sebaceous gland, can be intensively
      and selectively stained by ICG due to dye diffusion through pilosebaceous canal
      and its fast uptake by living microorganisms, by vital keratinocytes of
      epithelium of the canal and sebaceous duct, and by rapidly proliferating
      sebocytes, new technologies of soft and thermal acne lesions treatment that could
      be used in clinical treatment of acne were proposed.

PMID- 14677158
TI  - The interaction of lipopolysaccharides with phenothiazine dyes.
AB  - BACKGROUND AND OBJECTIVES: The difference in the photobactericidal efficacy of
      methylene blue and toluidine blue against gram-negative bacteria may result from
      their primary reaction with lipopolysaccharides (LPS) of the outer bacterial
      membrane. The aim of the present study was to compare the reactivity of these
      dyes with LPS extracted from different gram-negative bacteria. STUDY
      DESIGN/MATERIALS AND METHODS: The interactions of methylene blue and toluidine
      blue with LPS from Escherichia coli (E. coli), Pseudomonas aeruginosa (P.
      aeruginosa), Klebsiella pneumoniae (K. pneumoniae), and Serratia marcescens (S.
      marcescens) were studied spectrophotometrically in 0.45% saline. The dyes were
      used at the concentration of 10 microM. The concentrations of LPS ranged from 5
      100 microg/ml. RESULTS: Methylene blue and toluidine blue enter into a
      metachromatic reaction with the LPS resulting the in generation of dimers of
      methylene blue and higher aggregates of toluidine blue. The more significant
      hypochromic and hypsochromic effects in the reaction of the latter with LPS
      indicate a greater metachromatic efficacy of toluidine blue than methylene blue.
      The equilibrium constants of the metachromatic complex between toluidine blue and
      different LPS were calculated. The spectrophotometric titration of LPS with the
      dyes was used to estimate the equivalent weight of LPS. CONCLUSIONS: Toluidine
      blue interacts with LPS more significantly than methylene blue in vitro. This may
      be one of the main factors determining its greater photobactericidal efficacy
      against gram-negative bacteria.

PMID- 14677159
TI  - Photothermal detection of laser-induced damage in single intact cells.
AB  - BACKGROUND AND OBJECTIVE: Most of the studies of laser-induced damage do not
      analyze individual cells. Objective of this work was to evaluate local photo
      induced thermal phenomena in single cells at theoretical and experimental levels
      for developing the method for real-time detection of laser damage in intact
      cells. STUDY DESIGN/MATERIALS AND METHODS: Theoretical model of cell-laser
      interaction assumes local nature of photo-induced thermal effects and describes
      photodamage through bubble formation. Photothermal (PT) method was suggested for
      damage detection. Laser-induced damage was verified for individual cells with two
      techniques through detection of Trypan blue penetration into damaged cell.
      RESULTS: Specific PT responses from blast-transformed lymphocytes were identified
      independently as result of bubble formation and cell damage. Probability of cell
      damage was obtained for cells as function of laser pulse energy. CONCLUSIONS: The
      Laser load test (LLT) was suggested for real-time detection of damage, damage
      threshold measurement, and investigation of intact single cells.

PMID- 14677160
TI  - Efficacy of different therapy regimes of low-power laser in painful
      osteoarthritis of the knee: a double-blind and randomized-controlled trial.
AB  - BACKGROUND AND OBJECTIVES: A prospective, double-blind, randomized, and
      controlled trial was conducted in patients with knee osteoarthritis (OA) to
      evaluate the efficacy of infrared low-power Gallium-Arsenide (Ga-As) laser
      therapy (LPLT) and compared two different laser therapy regimes. STUDY
      DESIGN/MATERIALS AND METHODS: Ninety patients were randomly assigned to three
      treatment groups by one of the nontreating authors by drawing 1 of 90 envelopes
      labeled 'A' (Group I: actual LPLT consisted of 5 minutes, 3 J total dose +
      exercise; 30 patients), 'B' (Group II: actual LPLT consisted of 3 minutes, 2 J
      total dose + exercise; 30 patients), and 'C' (Group III: placebo laser group +
      exercise; 30 patients). All patients received a total of 10 treatments, and
      exercise therapy program was continued during study (14 weeks). Subjects,
      physician, and data analysts were unaware of the code for active or placebo laser
      until the data analysis was complete. All patients were evaluated with respect to
      pain, degree of active knee flexion, duration of morning stiffness, painless
      walking distance and duration, and the Western Ontario and Mc Master Universities
      Osteoarthritis Index (WOMAC) at week 0, 6, 10, and 14. RESULTS: Statistically
      significant improvements were indicated in respect to all parameters such as
      pain, function, and quality of life (QoL) measures in the post-therapy period
      compared to pre-therapy in both active laser groups (P < 0.01). Improvements in
      all parameters of the Group I and in parameters, such as pain and WOMAC of the
      Group II, were more statistically significant when compared with placebo laser
      group (P < 0.05). CONCLUSIONS: Our study demonstrated that applications of LPLT
      in different dose and duration have not affected results and both therapy regimes
      were a safe and effective method in treatment of knee OA.

PMID- 14677161
TI  - Efficacy of low level laser therapy in myofascial pain syndrome: an algometric
      and thermographic evaluation.
AB  - BACKGROUND AND OBJECTIVES: The efficacy of low level laser therapy (LLLT) in
      myofascial pain syndrome (MPS) seems controversial. Our aim was to clarify the
      effect of LLLT in MPS by using algometry and thermography. STUDY DESIGN/MATERIALS
      AND METHODS: Sixty-two patients with MPS having an active trigger point in the
      neck or upper back region were randomly divided into two equal groups according
      to therapy applied (group 1: LLLT + stretching exercises, group 2: stretching
      exercises alone). The outcome measures were pain measured with visual analogue
      scale (VAS), algometry on the trigger point, algometric difference, thermographic
      difference, and thermal asymmetry. Comparison was made within and between the
      groups pre- and post-therapeutically and 3 weeks after therapy. RESULTS: Mean
      pain values decreased more significantly in group 1 from baseline to 3 weeks
      follow up (7.54-3.06) while these values were 7.03-5.19 in group 2 (P < 0.05).
      Group comparisons revealed significant favorable differences in group 1 patients
      in terms of all other parameters at the first and the second evaluation post
      therapeutically (P < 0.05). CONCLUSIONS: LLLT seemed to be beneficial for pain in
      MPS by using algometry and thermography.

PMID- 14677162
TI  - Comparison of the photostimulatory effects of visible He-Ne and infrared Ga-As
      lasers on healing impaired diabetic rat wounds.
AB  - BACKGROUND AND OBJECTIVES: In this study, the ability of photostimulation to
      promote healing of impaired wounds was investigated using a Ga-As laser in rats
      with experimental diabetes and the results were compared with previously reported
      findings of the effects of a He-Ne laser on the repair of healing-impaired
      diabetic rat wounds 1. STUDY DESIGN/MATERIALS AND METHODS: Diabetes was induced
      in male rats by streptozotocin injection following which two full thickness punch
      wounds of 6-mm diameter were created in the skin, one on either side of the spine
      of each animal. The left wound of each animal was treated with infrared radiation
      at 904 nm produced by a Ga-As laser at an energy density of 1.0 J/cm(2). The
      right wound of each animal served as the control. The wounds were treated with a
      laser 5 days a week for 3 weeks. Following animal sacrifice, the strips of skin
      containing the wound sites were collected and analyzed. RESULTS: The results from
      the biomechanical analysis indicated that the Ga-As laser used in this study
      significantly increased wound tensile strain and toughness compared to the
      control wounds. Marginal increases in wound tensile strength (9%) and stress (7%)
      were observed in the Ga-As laser-treated wounds compared to the controls. No
      significant changes were found in Young's modulus and energy absorption capacity
      between the control and laser-treated wounds. Analysis of wound collagen revealed
      a significant increases in total collagen (14%), salt soluble collagen (31%),
      acid soluble (14%), and insoluble collagen (50%) with simultaneous decrease in
      pepsin soluble collagen (19%) in the Ga-As laser-treated wounds compared to
      controls. Comparisons of these results with the earlier findings revealed that
      the He-Ne laser appears to be superior to the Ga-As laser, at the parameters of
      treatment tested, in promoting the wound healing in diabetic rats. CONCLUSIONS:
      The differences in stimulatory effects noted between the He-Ne and Ga-As lasers
      suggest that the photochemical response the cells for each laser may depend on
      the wavelength and coherent properties of the electromagnetic radiation.

PMID- 14677163
TI  - Effects of the Ga-As laser irradiation on myonecrosis caused by Bothrops Moojeni
      snake venom.
AB  - BACKGROUND AND OBJECTIVES: Viper snake envenoming induces in the victims systemic
      coagulopathy, and severe local tissue damage such as edema, hemorrhage, intense
      pain, and myonecrosis. Serumtherapy and other first-aid managements are
      ineffective in neutralizing these local effects. The effects of the gallium
      arsenide (Ga-As) laser irradiation on mice gastrocnemius injected intramuscularly
      (i.m.) with Bothrops moojeni snake venom were investigated. STUDY
      DESIGN/MATERIALS AND METHODS: Macroscopical, histopatological, and myonecrosis
      quantification through serum creatine kinase (CK) evaluation was done at 3, 12,
      and 24 hours (two, five, and eight irradiation sessions, 4 J/cm(2), 1 minute 32
      seconds per period, respectively), were done after the venom or saline injection,
      and in venom-unirradiated mice. RESULTS: In unirradiated gastrocnemius, the venom
      induced massive hemorrhage, vascular congestion, time-progressing myonecrosis,
      edema, abundant inflammatory infiltrate, and high CK serum levels. Ga-As
      irradiation significantly decreased the amount of myonecrosis in all the periods
      tested (P < 0.05). CONCLUSIONS: The laser treatment significantly inhibited the
      ability of B. moojeni venom to rapidly disrupt the integrity of the plasma
      membrane.

PMID- 14677164
TI  - Treatment of cervical dentin hypersensitivity using neodymium: Yttrium-aluminum
      garnet laser. Clinical evaluation.
AB  - BACKGROUND AND OBJECTIVE: The incidence of cervical dentinal hypersensitivity is
      related to the high number of non-carious cervical lesions. This clinical
      research was developed in order to evaluate the Nd:YAG laser treatment of
      cervical dentin hypersensitivity after attempting the removal and control of
      etiologic factor after two different stimuli. STUDY DESIGN/MATERIALS AND METHODS:
      Twenty patients participated in this study in a total of 145 teeth, where 104
      received the Nd:YAG laser treatment and 41 remained as control. RESULTS: The
      results showed that there was statistically significant reduction of
      hypersensitivity as for the groups that received the treatment with Nd:YAG laser,
      as for the control teeth. However, the reduction of cervical dentinal
      hypersensitivity was statistically greater when there was the association of the
      removal of etiologic factors with the application of Nd:YAG laser. CONCLUSIONS:
      We concluded that the laser irradiation was effective in the treatment of
      cervical dentin hypersensitivity after 6 months.

PMID- 14677165
TI  - Leisure time physical activity and well-being: learning from people living with
      arthritis.

PMID- 14677166
TI  - Neuroendocrine immune perturbations in rheumatoid arthritis: causes,
      consequences, or confounders in the disease process?

PMID- 14677167
TI  - The gut in ankylosing spondylitis and other spondyloarthropathies: inflammation
      beneath the surface.

PMID- 14677168
TI  - CANDOO and CANOAR, CORRONA and more: advancing therapeutics through layered-in
      clinical data collection and feedback at the point of care.

PMID- 14677169
TI  - WHO-ILAR COPCORD perspectives past, present, and future.

PMID- 14677170
TI  - Do the clinical responses and complications following etanercept or infliximab
      therapy predict similar outcomes with the other tumor necrosis factor-alpha
      antagonists in patients with rheumatoid arthritis?
AB  - OBJECTIVE: To study a group of 29 patients with rheumatoid arthritis (RA) who
      have been treated with both tumor necrosis factor (TNF)-alpha antagonists,
      etanercept and infliximab and to determine the correlation of responses and
      complications seen in these patients. METHODS: Patients' responses to and
      complications from either treatment were reviewed retrospectively by determining
      the joint counts, acute phase reactants, as well as occurrences of infection,
      hypersensitivity, and cytopenia. The correlation of responses and complications
      was determined using phi coefficients and exact p values. RESULTS: There was no
      correlation between the joint count responses (exact p value for correlation
      coefficient, 0.70) and acute phase reactant responses (exact p value 0.14) with
      the use of etanercept and infliximab in the same patient. There was no
      correlation between the occurrences of drug hypersensitivity reactions (exact p
      value 0.20) or infectious complications (exact p value 1.00). However, the
      occurrence of anemia with the use of one TNF-alpha antagonist was correlated with
      a similar occurrence with the use of the other antagonist (exact p value 0.007).
      CONCLUSION: Our study indicates that patients who fail to respond to one TNF
      alpha antagonist can respond to the other antagonist. Furthermore, there appears
      to be no contraindication to using one TNF-alpha antagonist for patients who have
      developed hypersensitivity reactions to the other. The infections observed in our
      study were generally mild and did not necessarily recur with the use of the
      second antagonist. In contrast, anemia, when present with the use of one agent,
      was likely to occur with the use of the second agent.

PMID- 14677171
TI  - Variability of RANKL and osteoprotegerin staining in synovial tissue from
      patients with active rheumatoid arthritis: quantification using color video image
      analysis.
AB  - OBJECTIVE: To assess the interpatient, interbiopsy, and intrabiopsy variability
      of receptor activator of nuclear factor kB ligand (RANKL) and osteoprotegerin
      (OPG) immunostaining within synovial tissue from rheumatoid knee joints with
      active synovitis, using digital image analysis. METHODS: Synovial biopsy
      specimens were obtained from patients with rheumatoid arthritis (RA) and active
      synovitis. Immunohistologic analysis was performed on frozen synovial tissue
      biopsy specimens from 6 patients using a monoclonal antibody (Mab) to detect
      RANKL (626) or OPG (805 or 8051). Patients with a minimum of 4 synovial biopsies
      were included in the study. Sections were evaluated by computer assisted image
      analysis to assess between-patient, between-biopsy, and intra-biopsy variability
      of OPG and RANKL protein expression. The study was designed to deliberately
      maximize the variability. RESULTS: Computerized image analysis of staining with
      Mab to RANKL and OPG revealed variance for each antibody across the 3 components
      of the total variability. CONCLUSION: Our study shows that variability in
      synovial immunostaining of RANKL and OPG protein is a significant and complex
      problem. We discuss methods to reduce this variability and suggest that the
      auspices of OMERACT may be employed to advance the study of synovium in
      collaborative international studies.

PMID- 14677172
TI  - Longterm observational study of methotrexate use in a Dutch cohort of 1022
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: To study which factors are associated with longterm methotrexate (MTX)
      use in rheumatoid arthritis (RA). METHODS: All patients with RA who had started
      MTX after January 1, 1993, were selected from a regional hospital based
      registration system. Data on demographic and clinical features were retrieved
      through chart review. By means of life table analysis and Cox regression
      analysis, MTX survival and the relation between demographic variables, clinical
      features, and MTX survival were studied. RESULTS: A total of 1072 MTX treatment
      episodes in 1022 patients were analyzed. The cumulative MTX survival probability
      after 5 years was 64%, and after 9 years was 50%. Univariate analysis showed a
      significant relation between MTX survival probability and folic acid
      supplementation, attending rheumatologist, concurrent prednisolone use,
      concurrent sulfasalazine use, and the number of previous disease modifying drugs.
      In the multivariate analysis folic acid supplementation, attending
      rheumatologist, and concurrent prednisolone use remained significantly related to
      MTX survival. Age, disease duration, and creatinine clearance were not.
      CONCLUSION: In this retrospective study of 1022 patients with RA the cumulative
      MTX survival probability was 64% after 5 years and 50% after 9 years. Folic acid
      supplementation and to a lesser extent prednisolone were associated with a longer
      MTX survival. In addition, treatment strategies of individual rheumatologists
      influenced MTX survival.

PMID- 14677173
TI  - Mepacrine inhibits matrix metalloproteinases-1 (MMP-1) and MMP-9 activation in
      human fibroblast-like synoviocytes.
AB  - OBJECTIVE: Matrix metalloproteinases (MMP) are enzymes known to be involved in
      normal physiological and in many pathological conditions. Rheumatic diseases are
      among the ailments where MMP have been shown to exert detrimental effects.
      Mepacrine is used alone or in combination with other drugs to treat lupus and
      other rheumatic diseases. We investigated whether mepacrine's beneficial effects
      might be due to its influence on MMP. METHODS: Human fibroblast-like synoviocytes
      were used to study the effect of mepacrine on phorbol myristic acetate (PMA)
      induced activation of MMP. Western blot, reverse transcription-polymerase chain
      reaction, and electrophoretic mobility shift assay (EMSA) experiments were used
      to investigate the effect of mepacrine. RESULTS: Mepacrine selectively inhibited
      MMP in human fibroblast-like synoviocytes. Mepacrine inhibited MMP-1 as well as
      MMP-9, but had no effect on MMP-3 at the mRNA level. Possible mechanisms to
      explain these findings were investigated, and it was found that mepacrine had a
      strikingly different effect on c-Jun, as opposed to c-Fos activation. While
      mepacrine treatment alone led to increased concentrations of c-Jun within the
      nuclear compartment, c-Fos translocation into the nucleus was blocked in
      synoviocytes treated with mepacrine and stimulated with PMA. Accordingly, EMSA
      showed reduced AP-1 binding in mepacrine treated synoviocytes. These results
      imply that the observed effects of mepacrine on immediate early genes resulted in
      reduced AP-1 binding. That ultimately led to a selective suppression of genes
      that rely on unhindered assembling of these transcription factors for their
      activation. CONCLUSION: Selective inhibition of MMP by mepacrine might in part
      explain the beneficial effects of this drug in the treatment of certain diseases.

PMID- 14677174
TI  - Abnormal levels of serum dehydroepiandrosterone, estrone, and estradiol in men
      with rheumatoid arthritis: high correlation between serum estradiol and current
      degree of inflammation.
AB  - OBJECTIVE: Men with rheumatoid arthritis (RA) have a higher than normal frequency
      of low testosterone levels, but not much is known about other sex hormones. We
      investigated serum levels of estradiol, estrone, and the adrenal androgen
      dehydroepiandrosterone (DHEAS) in men with RA and evaluated the association of
      various disease variables with these sex hormones. METHODS: Inflammatory
      activity, measured as disease activity score including 28 joints (Disease
      Activity Score 28), and degree of disability, measured with the Health Assessment
      Questionnaire, were estimated in 101 men with RA. Presence of erosions,
      rheumatoid factor (RF), smoking habits, and body mass index were recorded. DHEAS
      (not measured in patients taking glucocorticoids), estradiol, and estrone were
      measured in patients and in healthy controls. RESULTS: DHEAS and estrone
      concentrations were lower and estradiol was higher in patients compared with
      healthy controls. DHEAS differed between RF positive and RF negative patients.
      Estrone did not correlate with any disease variable, whereas estradiol correlated
      strongly and positively with all measured indices of inflammation. CONCLUSION:
      Men with RA had aberrations in all sex hormones analyzed, although only estradiol
      consistently correlated with inflammation. The high levels of estradiol may have
      positive implications for bone health. The low levels of estrone and DHEAS may
      depend on a shift in the adrenal steroidogenesis towards the glucocorticoid
      pathway, whereas increased conversion of estrone to estradiol seemed to be the
      cause of the high estradiol levels.

PMID- 14677175
TI  - Predictive factors of 5-year health assessment questionnaire disability in early
      rheumatoid arthritis.
AB  - OBJECTIVE: To determine prognostic factors of disability in early rheumatoid
      arthritis (RA) and to investigate the radiological and functional course of the
      disease. METHODS: A total of 191 patients with early RA (diagnosed for less than
      one year) according to American College of Rheumatology criteria were followed
      prospectively for 5 years. At baseline and at endpoint, Stanford Health
      Assessment Questionnaire (HAQ) scores and radiological scores (Sharp's score
      modified by van der Heijde) were performed. Correlations between numerous
      baseline data and HAQ score at endpoint were analyzed, using nonparametric tests.
      A multilinear regression model was performed to select independent prognostic
      factors of HAQ disability. RESULTS: During the 5-year followup, mean HAQ
      decreased from 1.3 (+/- 0.7) to 0.6 (+/- 0.6). There were 98 (65.3%) patients
      with a score > 1 point at baseline, but only 46 (27.4%) after 3 years and 34
      (21.8%) after 5 years. Moreover, 90% of the patients had an improvement of the
      disability score. Final HAQ disability was associated with baseline values of HAQ
      score, Pain, Ritchie index, tender joint count, Disease Activity Score,
      erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and erosion.
      Multivariate analysis selected baseline HAQ score, Ritchie index, ESR, CRP, and
      presence of erosion as independent prognostic factors of HAQ disability. The
      probability cutoff in the logistic model was selected to minimize the sum of
      false positive and false negative values: negative predictive value = 92.71%,
      positive predictive value = 46.15%, p = 0.408. Sex, age, IgM and IgA rheumatoid
      factors, other tested autoantibodies, and HLA class II genes did not contribute
      significantly to prediction of the disability after 5 years. At baseline, mean
      scores were 3.6 units (+/- 7.7) for total radiological score, 1.7 (+/- 4.5) for
      erosion score, and 1.9 (+/- 3.7) for joint space narrowing score. After 5 years,
      they were 17.9 +/- 22.3, 6.9 +/- 9.5, and 11.0 +/- 15.4, respectively. No erosion
      was present at the start in 58.0% of patients, compared to 24.2% and 22.4% at 3
      and 5 years. Global radiographic progression concerned 87 patients (55.8%) during
      the 5 years. CONCLUSION: During the first 5 years of RA, radiological damage
      increased progressively in half of the patients, whereas HAQ disability improved
      in most of them during the same period of time and could be predicted by baseline
      values of HAQ score, Ritchie index, ESR, CRP, and presence (or absence) of
      erosion.

PMID- 14677176
TI  - Relation between body mass index and radiological progression in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To determine if there is an influence of body mass index (BMI) on the
      radiological progression in early and longer duration rheumatoid arthritis (RA).
      METHODS: Fifty-four patients with RA were observed in a progressive 2 year
      followup for radiological progression of joint damage. At the beginning of study,
      27 (50%) patients had a duration of complaints less than 6 months, grouped as
      early RA. BMI at the beginning and end of the study were monitored, together with
      HLA-DRB1 alleles, initial joint erosions, duration of disease, age, sex,
      erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Outcome was
      defined as radiographic damage according to yearly increase of Larsen score.
      RESULTS: Increased radiographic joint damage of patients was significantly
      correlated with lower BMI at the beginning of the study (r = 0.363, p < 0.05),
      the presence of initial joint erosions (r = 0.341, p < 0.01), ESR (r = 0.315, p <
      0.05), and CRP at study entry (r = 0.427, p < 0.01). Patients with an increase of
      Larsen score > or = 5.8/year were found to have a lower weight at the beginning
      of their complaints (BMI 24.8 +/- 4.7 vs 27.8 +/- 3.8; p < 0.05) as well as after
      the time of observation (BMI 24.6 +/- 3.7 vs 27.6 +/- 4.9; p < 0.05). Stepwise
      logistic regression analysis revealed a BMI < 27 at the beginning of disease
      (beta = 2.04, p = 0.003, odds ratio = 7.69), the presence of HLA-DR4 shared
      epitope (beta = 1.76, p = 0.015, OR 5.82), and joint erosions at study entry
      (beta = 1.56, p = 0.044, OR 4.78) as significant predictors for rapid joint
      damage. CONCLUSION: Together with the presence of HLA-DR4 shared epitope and
      erosive disease at study entry, a low BMI at the beginning of RA was found in
      association with higher radiographic progression in RA. Accordingly, BMI could be
      of interest as a sensitive and inflammation-independent predictor for
      radiological outcome of RA.

PMID- 14677177
TI  - Changes in 3D joint kinematics support the continuous use of orthoses in the
      management of painful rearfoot deformity in rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the efficacy of custom foot orthoses for the management of
      painful rearfoot valgus in patients with rheumatoid arthritis (RA). METHODS:
      Patients were randomized to receive custom-manufactured rigid carbon graphite
      foot orthoses (RA-orthosis) or enter a control group (RA-control) receiving no
      orthotic intervention. Three-dimensional (3D) kinematics were measured at the
      ankle joint complex (AJC) using an electromagnetic tracking (EMT) system under
      barefoot, shod, and orthosis walking conditions. Previously established normal 3D
      kinematic data were used to descriptively compare motion patterns in both RA
      groups and statistical analyses were performed on integrals of motion-time for
      each axis of rotation from data collected at baseline, 3, 6, 12, 18, 24, and 30
      months. RESULTS: Compared with healthy control subjects, all patients with RA
      demonstrated excessive subtalar joint eversion motion through the stance phase of
      gait (p < 0.0001) coupled with excessive internal leg rotation (p < 0.0001).
      Custom-manufactured orthoses significantly reduced eversion through stance (p =
      0.009) and re-established equilibrium of motion relative to neutral joint
      position. Correcting the frontal plane component of the deformity did not lead to
      a significant reduction in internal leg rotation (p = 0.294). The devices had no
      effect on tibiotalar dorsiflexion/plantarflexion (p = 0.960). Prospectively, the
      rigid orthoses maintained and then improved the reduction in cumulative subtalar
      eversion motion (p < 0.0001). Minimal changes in cumulative subtalar component
      eversion and internal leg rotation were recorded for both RA groups when walking
      barefoot but the effect was significantly less for the RA-control group. From 12
      months onwards, internal leg rotation started to decrease, suggesting re-coupling
      of motion, but the overall motion pattern remained abnormal in comparison with
      normal reference values. CONCLUSION: These results support the continuous use of
      custom-manufactured foot orthoses to correct deformity and optimize AJC function
      in RA patients with early painful deformity of the rearfoot.

PMID- 14677178
TI  - Bone mineral density in premenopausal women with systemic lupus erythematosus.
AB  - OBJECTIVE: To study bone mineral density (BMD) in premenopausal women with
      systemic lupus erythematosus (SLE) and to evaluate the influence of disease
      activity and use of corticosteroids. METHODS: A cross-sectional study on BMD of
      118 premenopausal women with SLE. Patients were divided into 2 groups, 74 who had
      been treated with corticosteroids and 44 who had not. BMD at lumbar spine,
      femoral neck, and trochanter was measured. RESULTS: BMD in patients without and
      with corticosteroid treatment was 1.13 +/- 0.13 vs 1.05 +/- 0.14 g/cm2 (p =
      0.005) at lumbar spine, 0.92 +/- 0.12 vs 0.86 +/- 0.12 g/cm2 (p = 0.005) at
      femoral neck, and 0.78 +/- 0.13 vs 0.72 +/- 0.12 g/cm2 (p = 0.014) at trochanter,
      respectively. Stepwise multilinear regression analysis showed that corticosteroid
      exposure was independently associated with decreased BMD in the corticosteroid
      treated patients (r2 = 7% for lumbar and 6.6% for trochanter model). No
      significant difference in BMD in corticosteroid treated patients appeared when
      they were subgrouped according to whether they were taking calcium supplements.
      Prevalence of osteoporosis at lumbar spine in corticosteroid treated patients was
      1.4%, and was lower than reported for age and sex matched Caucasians. CONCLUSION:
      BMD measurements were significantly lower in premenopausal SLE patients who had
      had corticosteroid treatment than those who had not. There was a negative
      correlation between BMD and corticosteroid therapy, but not disease activity.
      Prevalence of osteoporosis, based on lumbar spine BMD, was lower than that
      reported in Caucasians.

PMID- 14677179
TI  - A role for TARC/CCL17, a CC chemokine, in systemic lupus erythematosus.
AB  - OBJECTIVE: The Th2-type CC chemokine thymus and activation-regulated chemokine
      (TARC/CCL17) is one of the high affinity ligands for CCR4, a chemokine receptor
      predominantly expressed by Th2 cells. We examined serum and plasma concentrations
      of TARC/CCL17 in patients with systemic lupus erythematosus (SLE). METHODS: Serum
      and plasma levels of TARC/CCL17 and plasma levels of monocyte chemoattractant
      protein-1 (MCP-1/CCL2) and macrophage-derived chemokine (MDC/CCL22) in patients
      with SLE were determined by ELISA. RESULTS: There were significant differences in
      the plasma concentrations of TARC/CCL17 between the patients with untreated SLE
      and treated SLE (p < 0.001), rheumatoid arthritis (RA) (p < 0.001), and healthy
      controls (p < 0.001). In addition, the plasma levels of TARC/CCL17 correlated
      with the class of lupus nephritis (higher in class I or II than in class III or
      IV). There was close correlation between plasma levels of MDC/CCL22 and
      TARC/CCL17. There was no correlation between plasma levels of MCP-1/CCL2 and
      TARC/CCL17. CONCLUSION: TARC/CCL17 may be a useful serological marker and may
      facilitate an assessment of the degree of disease activity in SLE. The
      development of SLE is closely related to the elevation of plasma TARC/CCL17
      levels.

PMID- 14677180
TI  - A critical evaluation of enzyme immunoassay kits for detection of antinuclear
      autoantibodies of defined specificities. III. Comparative performance
      characteristics of academic and manufacturers' laboratories.
AB  - OBJECTIVE: To analyze the performance of different commercial enzyme immunoassay
      (EIA) kits for measuring antinuclear antibodies (ANA) specific for dsDNA, SSB/La,
      Sm, and Scl-70. METHODS: EIA kits for detection of ANA from 9 commercial
      manufacturers were evaluated. The manufacturers were advised that they would be
      sent coded sera containing mixtures of the Arthritis Foundation/Centers for
      Disease Control reference reagents, and that they were to use their own test kits
      to analyze the antibody specificities of these sera and to report the data, in
      optical density (OD) units or their equivalent. Independently, 12 investigators
      in academic institutions who have done research in this field agreed to
      participate in a parallel study. The concentration of the antibodies and the
      specificities were blinded to the analysts and the coefficients of variation (CV)
      were computed for each participant. RESULTS: There were statistically significant
      differences between laboratories in terms of CV for all 9 kits tested. With the
      exception of one kit, there were no significant CV differences between the
      various autoantibody kits provided by each manufacturer and, with the exception
      of kits from 2 manufacturers, there were no significant differences between the
      various antibody kits in terms of reproducibility (CV). From the point of view of
      interlaboratory variability, manufacturers could be separated into either a high
      or low performance group. CONCLUSION: We found a disconcertingly large range of
      performance characteristics in the various laboratories, which could be quite
      detrimental in routine utilization of EIA ANA kits. Clinicians should be aware of
      the performance issues raised in our study, and should know and be involved in
      how their service laboratory assesses its own performance and the performance of
      commercial testing systems utilized. Manufacturers and clinical laboratories need
      to exercise constant quality assurance and surveillance of kit performance in the
      hands of medical laboratory technologists involved in routine testing.

PMID- 14677181
TI  - Pentoxifylline in the treatment of refractory nephrotic syndrome secondary to
      lupus nephritis.
AB  - OBJECTIVE: To evaluate the efficacy of pentoxifylline in the treatment of
      refractory nephrotic syndrome secondary to lupus nephritis. METHODS: We studied
      11 patients who met the following inclusion criteria: (1) systemic lupus
      erythematosus (SLE) according to the American College of Rheumatology criteria;
      (2) lupus nephritis class III, IV, or V according to the World Health
      Organization; (3) proteinuria in the nephrotic range (> or = 3 g/24 h) for at
      least 6 months despite treatment. All patients received pentoxifylline 800-1600
      mg/day. Clinical and laboratory data, including creatinine, urine test,
      creatinine clearance, and 24-h urinary protein, were collected monthly for 6
      months. No changes in treatment were allowed, except for alterations in the dose
      of prednisone. RESULTS: All patients had received corticosteroids and
      immunosuppressants for at least 6 months. All patients showed a decrease in
      proteinuria concentrations after use of pentoxifylline from a median of 5.5 to
      2.0 (p = 0.003). No patient discontinued the drug due to side effects. One
      patient had nausea and one had anxiety that disappeared after decreasing the
      dosage. CONCLUSION: Pentoxifylline seems to be effective in the treatment of
      refractory nephrotic syndrome secondary to lupus nephritis.

PMID- 14677182
TI  - The presence of multiple prothrombotic risk factors is associated with a higher
      risk of thrombosis in individuals with anticardiolipin antibodies.
AB  - OBJECTIVE: To explore the effect of multiple prothrombotic risk factors in
      individuals with anticardiolipin antibodies (aCL), we evaluated immunologic,
      coagulation, and genetic prothrombotic abnormalities in a cohort of individuals
      with different aCL titers. METHODS: We recruited 87 individuals into 4 categories
      (normal, low, intermediate, or high) based on their baseline IgG aCL (aCL-IgG)
      titers. We measured at followup: repeat aCL-IgG, IgM aCL (aCL-IgM), antibodies to
      beta2-glycoprotein I (anti-beta2-GPI), lupus anticoagulant (LAC) antibodies,
      protein C, protein S, activated protein C resistance, factor V506 Leiden
      mutation, methyl tetrahydrofolate reductase (MTHFR) C677T genotype, and
      prothrombin 20210A gene mutation. Thrombotic events were confirmed. RESULTS: At
      recruitment, 20 individuals were negative for aCL-IgG and 67 were positive (22
      low, 20 intermediate, and 25 high titer). Twenty of the 87 participants had
      experienced a previous thrombotic event: 4 in the aCL-IgG negative group and 16
      in the aCL-IgG positive group. Among the 87 individuals, the number of those with
      concomitant prothrombotic risk factors was as follows: 5 had no other
      prothrombotic risk factors, 32 had 1 risk factor, 24 had 2 risk factors, 10 had 3
      risk factors, 10 had 4 risk factors, and 6 had 5 risk factors. Thrombotic events
      were observed in 20%, 13%, 33%, 10%, 30%, and 50% of these groups, respectively,
      and the odds ratio associated with a previous thrombotic event was 1.46 per each
      additional prothrombotic risk factor (95% confidence interval: 1.003-2.134).
      CONCLUSION: In individuals with positive aCL-IgG, we observed an association
      between the number of prothrombotic risk factors and history of thrombotic
      events.

PMID- 14677183
TI  - HLA class II alleles in systemic sclerosis patients with anti-RNA polymerase
      I/III antibody: associations with subunit reactivities.
AB  - OBJECTIVE: To examine HLA class II gene associations with anti-RNA polymerase
      (RNAP) I/III antibody responses in patients with systemic sclerosis (SSc).
      METHODS: HLA-DRB1, DRB3, DRB4, and DQB1 alleles were determined using polymerase
      chain reaction-based methods in 257 SSc patients (129 Japanese and 128
      Caucasians) and 271 race-matched regional controls (138 Japanese and 133
      Caucasians). Anti-RNAP I/III antibodies were identified by immunoprecipitation
      assay, and reactivities to individual RNAP subunits were determined by
      immunoblots using affinity-purified RNAP I, II, and III. RESULTS: Serum anti-RNAP
      I/III antibody was detected in 10 (8%) Japanese and 24 (19%) Caucasian patients
      with SSc. The presence of anti-RNAP I/III antibodies was associated with
      DRB1*0405, DRB4*01, and DQB1*0401 in Japanese, and with DRB3*02 in Caucasians,
      but these associations were weak and inconsistent between these 2 ethnic groups.
      When anti-RNAP I/III-positive SSc patients were divided into 2 groups based on
      the presence or absence of reactivities to individual RNAP subunit proteins,
      significant associations of anti-IIa/IIo reactivity with DRB3*02, anti-Ia
      reactivity with DRB1*04, anti-43-kDa subunit reactivity with DRB4*01, and anti-34
      kDa subunit reactivity with DRB1*15 were detected. These HLA associations with
      subunit reactivities were generally shared by Japanese and Caucasian patients
      with SSc. CONCLUSION: Our results suggest that in patients with SSc, anti-RNAP
      I/III antibodies are composed of subsets defined by combinations of reactivities
      to individual RNAP subunits having specific HLA class II correlations.

PMID- 14677184
TI  - Scleroderma patients with combined pulmonary hypertension and interstitial lung
      disease.
AB  - OBJECTIVE: Most studies differentiate scleroderma associated pulmonary
      hypertension and interstitial lung disease (ILD) as 2 separate pathological
      processes, concentrating on one or the other; however, many patients have both
      conditions. We studied the demographics, clinical features, and prognosis of
      individuals with both vascular and interstitial lung disease. METHODS: A
      retrospective cross-sectional study of 619 patients with scleroderma who had
      echocardiograph and pulmonary function testing performed within 6 months of one
      another. Echocardiography determined the presence of pulmonary hypertension, and
      pulmonary function testing documented restrictive ventilatory defect (RVD) as a
      marker of ILD. RESULTS: Among the study group, 139 (22.5%) patients had isolated
      RVD; 119 (19.2%) isolated pulmonary hypertension; and 112 (18.1%) patients had
      combined RVD and pulmonary hypertension. The individuals with combined RVD and
      pulmonary hypertension resembled patients with isolated RVD in that they had a
      high prevalence of diffuse skin involvement and antitopoisomerase positivity, but
      they were older at diagnosis and at disease onset (p < 0.01). Among those with
      mild RVD, 39.2% had pulmonary hypertension compared to those with severe RVD, in
      whom 51.4% had pulmonary hypertension. Compared to those without pulmonary
      disease, the mortality risk ratio for patients with isolated pulmonary
      hypertension, combined RVD and pulmonary hypertension, and isolated RVD was 2.9,
      2.4, and 1.61, respectively. CONCLUSION: Patients with combined scleroderma lung
      disease features are more likely to have diffuse disease, represent older
      patients, and have a prognosis similar to individuals with isolated pulmonary
      hypertension, and may represent a distinct subpopulation of scleroderma.

PMID- 14677185
TI  - Increased severity of lower urinary tract symptoms and daytime somnolence in
      primary Sjogren's syndrome.
AB  - OBJECTIVE: Functional antimuscarinic receptor autoantibodies have recently been
      described in both primary and secondary Sjogren's syndrome (SS) in a mouse
      bladder contraction assay. Most patients with these antibodies complained of
      severe lower urinary tract disturbances, which are not a recognized feature of
      SS. We compared the severity of self-reported urological symptoms, daytime
      somnolence, and fatigue between a cohort of patients with primary SS and controls
      with osteoarthritis (OA). METHODS: Female patients were recruited from
      rheumatology outpatient clinics at 2 hospitals. The American Urological Symptom
      Index (AUA-7), Epworth Sleepiness Scale, and FACIT-F fatigue self-administered
      instruments were employed. Results were obtained for 76 patients with primary SS
      and 43 controls (response rates 85% and 67%, respectively). The patient groups
      were matched for parity, hormone replacement and diuretic therapy, and number of
      bladder operations and urinary tract infections, although OA patients were
      slightly older. RESULTS: AUA-7 urological symptoms were more severe in patients
      with primary SS compared to OA controls (p = 0.039). Severe urological symptoms
      were reported by 61% of primary SS patients compared with 40% of OA controls.
      This difference was predominantly attributable to bladder irritability associated
      with urgency (p = 0.015) and not nocturia (p = 0.85). Epworth Sleepiness Scale
      scores were also more severe in primary SS patients compared to OA controls (p =
      0.02), independent of nocturia. The FACIT-F fatigue severity scores were not
      significantly different between patient groups (p = 0.14). CONCLUSION: Urological
      symptoms and daytime somnolence may be previously unrecognized symptoms of
      primary SS. These symptoms are consistent with functional disturbances of
      muscarinic receptors, possibly mediated by muscarinic receptor autoantibodies.

PMID- 14677186
TI  - Are women with Sjogren's syndrome androgen-deficient?
AB  - OBJECTIVE: We hypothesize that androgen deficiency is a critical etiologic factor
      in the pathogenesis of aqueous-deficient and evaporative dry eye in Sjogren's
      syndrome (SS). We investigated whether women with SS have a deficiency in total
      androgens. We also examined whether these patients have elevated serum
      concentrations of estrogens. METHODS: Blood was drawn from women with primary and
      secondary SS and age matched controls, and analyzed for steroid concentrations by
      gas and liquid chromatography-mass spectrometry. RESULTS: Our results show that
      women with SS are androgen-deficient. Concentrations of 5-androstene-3beta,17beta
      diol (5-diol), dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT),
      androsterone-glucuronide (ADT-G), and androstane-3a,17beta-diol-G (3alpha-diol-G)
      were all significantly reduced in SS sera relative to controls. In contrast, SS
      was not associated with significant alterations in the serum concentrations of
      testosterone, androstenedione, estrone, or 17beta-estradiol. These overall
      findings could not be attributed to the use of oral contraceptives or hormone
      replacement therapy, because the concentrations of 5-diol, DHEA, DHT, ADT-G and
      3a-diol-G were also decreased in patients with SS compared to levels in control
      women who were not taking exogenous estrogens. CONCLUSION: Our results show that
      women with SS are androgen-deficient.

PMID- 14677187
TI  - A 2-phase screening process for patients with Wegener's granulomatosis: a pilot
      study.
AB  - A 2-phase screening process for patients with persistent upper respiratory tract
      manifestations for the detection of Wegener's granulomatosis (WG) was tested in
      28 patients in this pilot study. One patient with WG was identified. A larger
      study is warranted.

PMID- 14677188
TI  - Serum cytokine profiles in patients with adult onset Still's disease.
AB  - OBJECTIVE: Adult onset Still's disease (AOSD) is a systemic inflammatory disorder
      characterized by fever, arthritis, and rash. Although the pathogenesis is not
      known, immunologically mediated inflammation occurs in active AOSD. To evaluate
      the pathogenesis and disease activity of AOSD, we measured serial serum
      concentrations of several cytokines in patients with active and inactive disease.
      METHODS: Seventeen patients diagnosed as having AOSD were enrolled. We analyzed
      clinical and laboratory findings retrospectively. Serial serum samples were
      obtained from 14 patients with active and inactive AOSD. Interleukin 18 (IL-18),
      soluble IL-2 receptor (sIL-2R), IL-6, interferon-g (IFN-g), and IL-8 were
      determined by ELISA. RESULTS: Serum levels of IL-18, IFN-g, and IL-8 were
      significantly higher in patients with AOSD than in healthy controls (p < 0.01),
      but there were no significant differences between patients with active and
      inactive AOSD. Serum sIL-2R levels tended to be higher in the active state than
      in healthy controls, but there was no statistically significant difference
      between the 2 groups. Serum sIL-2R levels decreased significantly with
      antiinflammatory therapy (p < 0.05). Serum IL-18 and sIL-2R levels correlated
      significantly with serum ferritin levels in the active AOSD group (p < 0.05).
      CONCLUSION: Overproduction of IL-18 may contribute to the pathogenic mechanism of
      AOSD, and serum sIL-2R levels may be used as a marker for monitoring disease
      activity in AOSD.

PMID- 14677189
TI  - Lymphocytic infiltration and expression of inducible nitric oxide synthase in
      human duodenal and colonic mucosa is a characteristic feature of ankylosing
      spondylitis.
AB  - OBJECTIVE: In patients with ankylosing spondylitis (AS), inflammatory processes
      have been detected in the ileal and colonic mucosa. The inducible isoform of
      nitric oxide synthase (iNOS) may be expressed early in the inflammatory process.
      We investigated iNOS activity and lymphocytic infiltration in the duodenum and
      colon in patients with AS and ulcerative colitis compared with controls. METHODS:
      Gastroscopy with duodenal biopsies and/or colonoscopy with biopsies were
      conducted in 42 patients with AS treated or not treated with nonsteroidal
      antiinflammatory drugs (NSAID), in 15 with ulcerative colitis, and in 46
      controls. Lymphocytic infiltration in the lamina propria and intraepithelial
      infiltration were quantified by histological score. iNOS expression was assessed
      by immunohistochemistry with monoclonal antibodies, and iNOS activity was
      determined by radiochemical assay. RESULTS: Endoscopic examination of the
      gastroduodenal or colonic mucosa did not reveal macroscopic lesions in the AS
      patients. In the duodenum, mucosal lymphocytic infiltration was found in 83.3% of
      the AS group compared to 48.6% of controls (p = 0.02), and was independent of the
      NSAID intake. Intraepithelial lymphocyte infiltration was increased in both
      duodenum and colon in AS patients compared to controls. iNOS activity in duodenum
      and colon and expression of iNOS protein in lamina propria inflammatory cells was
      increased in AS patients compared to controls. CONCLUSION: Lymphocytic
      infiltration and iNOS expression and activity were detected in duodenal and
      colonic mucosa from patients with AS. Such findings may indicate an inflammatory
      process in the small intestine and colon of patients with AS.

PMID- 14677190
TI  - The effect of control and self-medication of chronic gout in a developing
      country. Outcome after 10 years.
AB  - OBJECTIVE: We describe a 10 year observation of the effect of control of
      hyperuricemia compared with self-medication alone in patients with chronic gout.
      METHODS: We studied 299 consecutively self-referred Malayo-Polynesian men with
      chronic gout, mean age 35 +/- 14.3 SD years. Subjects comprised 228 cases with
      chronic gout without tophi or urolithiasis (Group 1) and 71 with those
      complications (Group 2). Attacks of acute gouty arthritis were treated with
      nonsteroidal antiinflammatory drugs (NSAID) and/or corticosteroids. After acute
      arthritis had settled, urate-lowering drugs were instituted in both groups
      combined with low dose colchicine and/or low dose NSAID for at least 0.5-2 years.
      Urate levels were maintained longterm at a mean of < 5 mg/dl. After 10 years, the
      dropouts were traced and evaluated for comparison with baseline and those who
      remained in the study. In Group 2 the urate-lowering drugs were continued.
      RESULTS: Control of gout and hyperuricemia was achieved in all patients who
      remained under control: 91.6% of the 299 patients for at least 2 years (short
      term), up to 5 years in 87.5% (medium term), and up to 10 years in 79.6%
      (longterm). In Group 1 (chronic gout without complication) only 36.8% had no
      attacks during 8 years, after they had tapered urate-lowering drug after the
      first 2 years of the study. In the 61 dropouts the intermittent symptomatic
      treatment and/or self-medication without longterm control of hyperuricemia
      resulted after 1 decade in chronic gout with more complications and associated
      conditions leading to increased morbidity, disability, and comorbidity, and 3
      early mortalities. CONCLUSION: By controlling hyperuricemia, improvement of the
      prognosis of chronic gout, comorbidity, and early death was achieved compared
      with self-medication alone. Self-medication in a developing country if continued
      unchecked may become a public health problem in a population with a high
      prevalence rate of gout.

PMID- 14677191
TI  - Celecoxib has a positive effect on the overall metabolism of hyaluronan and
      proteoglycans in human osteoarthritic cartilage.
AB  - OBJECTIVE: To assess the effects of celecoxib, a cyclooxygenase (COX-2) selective
      inhibitor, on the metabolism of hyaluronan (HA) and proteoglycans (PG) in human
      cartilage explants with midrange severity of osteoarthritis (OA). Results were
      compared with those of diclofenac, a non-selective COX inhibitor. METHODS:
      Cartilage specimens (OA grade 4-8 on Mankin's scale) were pulsed with 3H 
      glucosamine and chased in the absence or presence of 1-10 micro g/ml of celecoxib
      or diclofenac. After papain digestion, the labeled chondroitin sulfate and HA
      molecules were purified by anion-exchange chromatography. RESULTS: Diclofenac did
      not affect the metabolic balance of PG and HA whereas, in a relatively dose
      dependent manner, celecoxib increased the synthesis of HA and PG; celecoxib also
      reduced the net loss of labeled HA and PG molecules from cartilage explants.
      CONCLUSION: In short term in vitro cultures, celecoxib has a favorable effect on
      the overall metabolism of PG and HA. It is therefore unlikely that this drug
      would have a detrimental effect on articular cartilage during longterm
      administration. Further, celecoxib might help counteract the depletion of HA seen
      in OA cartilage.

PMID- 14677192
TI  - Do utility values and willingness to pay suitably reflect health outcome in hip
      and knee osteoarthritis? A comparative analysis with the WOMAC Index.
AB  - OBJECTIVE: To establish whether health utility (time trade-off, TTO) and
      willingness to pay (WTP) values reflect clinical health outcome as evaluated by
      the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) in hip and
      knee osteoarthritis (OA). METHODS: One hundred twenty-eight patients with OA
      attending a specialized arthritis clinic were interviewed about their
      socioeconomic characteristics and administered the TTO technique and the WOMAC.
      Their WTP for 2 hypothetical anti-osteoarthritic drugs was also investigated: the
      first drug was said to provide a significant improvement in WOMAC dimensions and
      the second a complete cure of the disease. WTP was elicited by both discrete
      choice and bidding game methods. Results. Answer rates were 89.1% for TTO, 98.4%
      for discrete-choice WTP for both scenarios, and 89.8% and 85.2% for bidding game
      WTP in the relief and the cure scenario, respectively. The mean TTO utility value
      was 0.84 (standard deviation 0.20). In discrete-choice, those accepting the bid
      had higher monthly income (EURO 1536.5 vs EURO 1060.1, p < 0.001, for the relief
      scenario and EURO 1449.3 vs EURO 1071.6, p < 0.001, for the cure scenario). With
      the bidding game format, WTP was positively correlated with income in both
      scenarios (r = 0.56, r = 0.55, p < 0.001). WTP measures differed equally between
      education and socioeconomic groups with those in favored groups consistently
      reporting higher WTP (Kruskal-Wallis tests statistics ranging from p < 0.01 to p
      < 0.001). Except for stiffness, WOMAC dimensions were correlated in the expected
      direction with TTO values (r = -0.27, p < 0.01 for pain and r = -0.36, r = -0.34,
      p < 0.001 for physical function and total score, respectively). CONCLUSION:
      Whereas they showed good feasibility, WTP measures poorly reflected clinical
      condition and were mainly related to economic status and ability to pay. TTO was
      correlated with the WOMAC dimensions and may be considered closer to clinical
      situations than WTP. However, concern arises regarding the homogeneity of the
      study sample in terms of clinical severity, which may have precluded the
      identification of a relationship between WTP and clinical status.

PMID- 14677193
TI  - Total incidence and distribution of inflammatory joint diseases in a defined
      population: results from the Kuopio 2000 arthritis survey.
AB  - OBJECTIVE: To study the incidence of inflammatory joint diseases in a defined
      population in Finland. METHODS: We collected data for the year 2000 on a
      population of 87,000 inhabitants of Kuopio, Finland, of whom 20% were < 16 years
      of age. Information about the study was given through a local newspaper, and
      subjects attended one health center and 2 local hospitals for study. Inclusion
      criteria were that subjects have at least one peripheral joint with synovitis or
      signs of inflammation in sacroiliac, glenohumeral, or hip joints on the first
      visit. Incidence rates were calculated according to the diagnosis on the first
      visit, except for children, for whom diagnoses were established after 3 months'
      followup. RESULTS: A total of 188 adult incident cases (138 women, 50 men) and 11
      children (8 girls, 3 boys) satisfied the inclusion criteria. The incidence of all
      arthritides was 230/100,000 (95% confidence interval 198.9-263.9) for the whole
      population; 271/100,000 (95% CI 233.7-312.7) for adults and 64/100,000 (95% CI
      31.7-113.8) for children. Among adults the annual incidence of rheumatoid
      arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive
      arthritis (ReA), other spondyloarthropathies (SpA), connective tissue disease
      (CTD), crystalline arthritis, viral arthritis, and undifferentiated arthritis
      were 36, 7, 23, 10, 13, 9, 19, 7, and 149/100,000, respectively. The mean age at
      diagnosis was 49.4 +/- 16.3 years for all cases of arthritis among adults, about
      the same for both women and men. The mean age at diagnosis was 59.7 years in RA,
      31.5 years in AS, 48.7 years in PsA, 38.0 years in ReA, 36.5 years in other SpA,
      36.1 years in CTD, 65.0 years in crystalline arthritis, 53.3 years in viral
      arthritis, and 48.3 years in undifferentiated arthritis. Four of 11 children had
      juvenile idiopathic arthritis (JIA). The incidence of JIA was 23/100,000 in the
      population < 16 years of age. Of the remaining cases, 3 children had antibodies
      against Sindbis (Pogosta) virus and 4 had a transient monoarthritis. CONCLUSION:
      The overall incidence of arthritides among adults was slightly higher than
      previously reported from Finland. The incidence rates in the child population are
      in agreement with previous figures. These data are useful in planning the
      provision of health care.

PMID- 14677194
TI  - The compliance-questionnaire-rheumatology compared with electronic medication
      event monitoring: a validation study.
AB  - OBJECTIVE: To validate the 19-item Compliance-Questionnaire-Rheumatology (CQR)
      against the "gold standard" in compliance measurement, electronic medication
      event monitoring. METHODS: Among 127 consenting patients, 81 with rheumatoid
      arthritis taking nonsteroidal antiinflammatory drugs (13 diclofenac, 20 naproxen)
      or disease modifying antirheumatic drugs (25 sulfasalazine, 23 methotrexate), 17
      patients with polymyalgia rheumatica taking prednisone, and 29 patients with gout
      taking daily prophylactic colchicine (n = 12) or the uric acid lowering drugs
      allopurinol (10) or benzbromaron (7), 104 used their medication from a regular
      medication bottle fitted with a special cap containing microelectronics capable
      of recording time and date of opening and closing, defined as a medication event.
      Data were processed for the following: (1) the percentage of prescribed
      medication events during the study period (taking compliance) and (2) the
      percentage of days with the prescribed number of medication events (i.e., correct
      dosing). Satisfactory compliance was defined as taking compliance or correct
      dosing > 80%, while unsatisfactory compliance was defined as taking compliance or
      correct dosing < or = 80%. All patients were informed about the monitoring, and
      were followed for 6 months (gout: 1 year). At baseline 85 patients completed a
      set of questionnaires including the 19-item CQR. RESULTS: A total of 85 patients
      who had complete questionnaire and electronic monitoring data were analyzed.
      Multiple linear regression analyses showed that the total, weighted CQR score
      significantly and adequately predicts taking compliance (p = 0.001, r2 = 0.46)
      and correct dosing (p = 0.004, r2 = 0.42). Discriminant analyses showed that
      specificity and sensitivity to detect good taking compliance were 95% and 62%,
      respectively, with a prevalence of good compliance of 52%. The predictive value
      to detect unsatisfactory taking compliance was 86%, and to detect good taking
      compliance was 83%. The likelihood ratio of the CQR-19 to detect low taking
      compliance was 11.6. Four items were especially predictive: fear of forgetting to
      take the drug, being able to function well, routines in daily life, and side
      effects (combined r2 = 0.35). CONCLUSION: These results support the validity of
      the Compliance Questionnaire Rheumatology.

PMID- 14677195
TI  - Leisure-time physical activity patterns and relationship to generalized distress
      among Canadians with arthritis or rheumatism.
AB  - OBJECTIVE: Little is known about the epidemiology and possible mental health
      benefits of leisure-time physical activity (LTPA) for persons with arthritis and
      other rheumatic conditions. We examined the prevalence of LTPA and its
      association to generalized distress among Canadians with rheumatic conditions.
      METHODS: The 1996-97 National Population Health Survey interview data from
      respondents with rheumatic conditions (n = 10,700) and persons with no chronic
      conditions (n = 19791) in the same age range (20-79 yrs) were selected for
      analyses. Self-reported data on forms and frequency of LTPA engaged in over the
      past 3 months were collected. Intensity of LTPA was expressed as total energy
      expenditure, with respondents classified as Active (> or = 3.0 kcal/kg/day),
      Moderate (1.5-2.9 kcal/kg/day), and Inactive (< 1.5 kcal/kg/day). Generalized
      distress was assessed using a subset of items from the Composite International
      Diagnostic Interview. RESULTS: Similar to persons with no chronic conditions,
      roughly 56% of persons with rheumatic conditions engaged in regular LTPA (12 or
      more 15-minute sessions per month). Only 13.2% of women and 18.9% of men with
      rheumatic conditions were sufficiently active at the level recommended to yield
      optimal health benefits. Both moderate and higher intensity LTPA was associated
      with less generalized distress. This relationship was more pronounced for women
      and for middle-aged and older patients with rheumatic conditions. CONCLUSION: A
      significant proportion of Canadians with rheumatic conditions are physically
      inactive. Even moderate intensity LTPA is associated with decreased generalized
      distress. Better efforts must be directed at promoting LTPA as part of the
      multidisciplinary management of this condition.

PMID- 14677196
TI  - Development of resource-use and expenditure questionnaires for use in
      rheumatology research.
AB  - OBJECTIVE: To develop a self-completion and postal resource-use and expenditure
      questionnaire for use in economic studies of early inflammatory polyarthritis
      (IP). METHODS: Identification of cost-generating events associated with early IP
      through a literature review and focus groups of IP patients and their partners.
      The information obtained was used to inform the development of self-completion
      postal resource-use and expenditure data collection instruments/questionnaires in
      terms of structure and content. Finally, the developed questionnaire was pilot
      tested and validated in populations in 2 geographically different areas. RESULTS:
      The main cost categories identified through the focus groups, and used in the
      development of the questionnaires, included forgone leisure time and activities,
      reliance on other people, life events, emotions, help with everyday chores,
      travel, and over-the-counter medication. Pilot-testing the questionnaires
      resulted in high unit and item response rates, and high acceptability and ease of
      completion by respondents, as well as generalizability to different geographical
      settings. Where possible, collected data were validated against alternative data
      sources, and agreement was good. CONCLUSION: Overall, resource-use and
      expenditure questionnaires developed in this study were shown to be highly
      acceptable to respondents, easy to complete, and generalizable to different
      geographical settings within the UK.

PMID- 14677197
TI  - Effects on growth and body composition of growth hormone treatment in children
      with juvenile idiopathic arthritis requiring steroid therapy.
AB  - OBJECTIVE: Decreased growth velocity and abnormal body composition including
      severe osteoporosis are common in glucocorticoid-treated patients with juvenile
      idiopathic arthritis (JIA). We evaluated the effects of recombinant human growth
      hormone (GH) given for 3 years on growth velocity, height standard deviation
      score (SDS), and body composition, together with potential adverse effects on
      glucose tolerance. METHODS: Thirteen patients received GH (0.46 mg/kg/week) for 3
      years. Body composition was assessed by dual-energy x-ray absorptiometry and
      glucose tolerance by annual oral glucose tolerance tests. RESULTS: Median growth
      velocity increased from 2.1 to 6.0 cm/year (p = 0.002) in the first year and
      remained higher than baseline in the second year of treatment. Height SDS did not
      change significantly (-4.6 SDS at baseline vs -4.3 SDS at study completion), but
      the growth response varied markedly across patients. Compared with baseline, lean
      mass increased by 33%, fat mass remained stable, and lumbar bone mineral density
      increased by 36.6%. Transient glucose intolerance developed in 6 patients, but
      glycosylated hemoglobin concentrations did not change significantly and diabetes
      mellitus did not occur. CONCLUSION: Treatment with GH restored linear growth
      without inducing catch-up growth, significantly improved body composition, and
      prevented further bone loss. Prolonged followup is needed to assess the benefits
      of GH and longterm consequences of hyperinsulinism.

PMID- 14677198
TI  - Nodular scleroderma: case report and literature review.
AB  - OBJECTIVE: To describe a unique case of scleroderma (SSc) presenting as multiple
      keloidal nodules and early-onset osteoarthritis (OA), and to summarize the
      clinical and serological data for 13 similar patients reported in the English
      literature since 1966. METHODS: MEDLINE review of the literature over a 35-year
      period (1966-2002) revealed 13 cases of nodular SSc. We describe a case of
      nodular SSc in a 40-year-old African-American male with localized SSc who
      developed progressive skin thickening and keloidal nodules on the arms, hands,
      chest, abdomen, and thighs with advanced osteoarthritis of the hips. RESULTS: In
      all 14 cases, diagnosis was made based on skin biopsy and evidence of keloid
      (nodule) formation. Ten cases occurred in women and 4 in men, with ages ranging
      from 9 to 66 years and a mean age of 38.9 years. The ethnicity of the patients
      was given in only 5 of the 13 previously reported cases. Including our patient, 4
      were of African descent, and 2 were Caucasian. Most patients had symptoms of SSc
      consisting of arthralgias (n = 10), sclerodactyly (n = 9), Raynaud's phenomenon
      (n = 8), digital pitting and/or calcinosis (n = 5), shortness of breath with
      pulmonary fibrosis (n = 5) or pulmonary hypertension (n = 1), dysphagia or reflux
      (n = 3), renal disease (n =3), and elevated erythrocyte sedimentation rate (n =
      3). CONCLUSION: Nodular SSc is a rare variant that presents with lesions that
      clinically resemble keloids. OA, as documented in the present case, does not
      appear to be a typical feature of nodular SSc.

PMID- 14677199
TI  - Severe Raynaud's phenomenon with yohimbine therapy for erectile dysfunction.
AB  - Yohimbine is a selective alpha-2 adrenergic antagonist that has been used in the
      pharmacologic management of erectile dysfunction (ED). We describe a patient with
      CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysfunction,
      sclerodactyly, and telangiectasia) who paradoxically experienced worsening of
      Raynaud's phenomenon when using yohimbine for ED.

PMID- 14677200
TI  - Atopic dermatitis as a side effect of anti-tumor necrosis factor-alpha therapy.

PMID- 14677201
TI  - Takayasu's arteritis: isolated aortitis.

PMID- 14677202
TI  - Influence of HLA-B27 on the clinical presentation of psoriatic arthritis.

PMID- 14677203
TI  - Frequency of the HLA-B27 alleles in Brazilian patients with AS.

PMID- 14677204
TI  - Findings of scientific misconduct.

PMID- 14677205
TI  - Findings of scientific misconduct.

PMID- 14677206
TI  - Branching out. A chance to protect the environment means a chance to save money.

PMID- 14677207
TI  - It's a process.

PMID- 14677208
TI  - A rural take on the route ahead. Interview by Robert Neil.

PMID- 14677209
TI  - Cynical hostility, depressive symptoms, and the expression of inflammatory risk
      markers for coronary heart disease.
AB  - Although the prognostic significance of depression and hostility has been
      established, little is known about how they operate together to influence disease
      processes. This study explored the independent and interactive relationships
      between these constructs and the expression of inflammatory markers implicated in
      the pathogenesis of coronary heart disease. One hundred adults completed measures
      of cynical hostility and depressive symptoms, and had blood drawn to assess serum
      levels of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha.
      Depression was directly related to inflammatory markers, but hostility was not. A
      significant interaction between hostility and depression emerged. Among
      participants scoring low in depressive symptoms, hostility was positively
      associated with interleukin-6 and tumor necrosis factor-alpha concentrations.
      Hostility's association with these inflammatory markers was much weaker among
      participants with moderate depressive symptoms, however, and virtually nil among
      participants with severe depressive symptoms. Neither depression nor hostility
      was associated with interleukin-1 beta concentrations. These findings highlight
      the importance of considering both the independent and interactive relationships
      among psychosocial characteristics involved in disease.

PMID- 14677210
TI  - The contribution of negative and positive illness schemas to depression in
      patients with end-stage renal disease.
AB  - This research examined the role of negative and positive illness schemas as
      predictors of depression in 109 ESRD patients who were recruited from dialysis
      clinics throughout the San Diego area. Specifically, the model evaluated whether
      negative and positive illness schemas would mediate the relationship between
      disease severity and depression, and social support and depression, in a cross
      sectional design. The model was tested with the Cognitive Depression Inventory
      (CDI), derived from the Beck Depression Inventory (BDI), and the full Beck as
      criterion variables. Hierarchical multiple regression analysis employing path
      analytic procedures revealed that while disease severity was unrelated to
      depression, negative illness schema contributed to higher BDI and CDI scores, and
      positive illness schema contributed to lower BDI and CDI scores. Furthermore,
      positive illness schema mediated the relationship between social support and
      depression in both the BDI and CDI models. The results illustrate the important
      contribution of illness schemas to depression in this life-threatening disease.

PMID- 14677211
TI  - Biomedical and psychosocial predictors of anginal frequency in patients following
      angioplasty with and without coronary stenting.
AB  - This study examined the contribution of biomedical and psychological variables in
      the report of anginal frequency at 6-week, 6- and 12-month follow-up in patients
      who received angioplasty with and without stent. Patients (N = 70) completed a
      battery of standardized questionnaries, including measures of depression,
      anxiety, and anger. Principal components analysis computed a single factor of
      negative emotion for use as a predictor in regression analyses. For the 6-week
      model, only baseline anginal frequency predicted anginal frequency. Negative
      emotion joined baseline anginal frequency in the prediction model for 6-month
      anginal frequency, and collectively accounted for 23% of the variance. For the 12
      month model, baseline anginal frequency, female sex, and negative emotions
      remained in the model, accounting for 46% of the variance in anginal frequency.
      These results highlight the importance of biomedical and psychosocial variables
      in predicting anginal frequency with psychological variables sustaining
      predictive value over the course of recovery.

PMID- 14677212
TI  - Adherence to colorectal cancer screening in mammography-adherent older women.
AB  - Colorectal cancer (CRC) is the third leading cause of cancer mortality among
      women. Screening can prevent the development of CRC or diagnose early disease
      when it can effectively be cured, however existing screening methods are
      underutilized. In this study, we examined the utility of an updated Health Belief
      Model to explain CRC screening adherence. The present study included 280 older
      women seeking routine mammography at a large, urban breast diagnostic facility.
      Overall, 50% of women were adherent to CRC screening guidelines. Multiple
      regression indicated that self-efficacy, physician recommendation, perceived
      benefits of and perceived barriers to screening accounted for 40% of variance in
      CRC screening adherence. However, there was no evidence for two mediational
      models with perceived benefits and perceived barriers as the primary mechanisms
      driving adherence to CRC screening. These findings may inform both future
      theoretical investigations as well as clinical interventions designed to increase
      CRC screening behavior.

PMID- 14677213
TI  - Self-reported health in HIV-positive African American women: the role of family
      stress and depressive symptoms.
AB  - This prospective study examined the association between stressful life events and
      self-reported health in 72 inner-city, low-income African American women with
      HIV. Depressive symptoms were examined as a potential mediator of this
      association. Findings indicated that family stressors predicted deterioration in
      self-reported health status over the 15-month assessment period. Additionally,
      the association between family stress and self-reported physical health was
      mediated by depressive symptoms such that the strength of the association between
      family stress and self-reported health was no longer statistically significant
      after depressive symptoms were entered in the model. This study suggests a
      potentially important target for prevention and intervention efforts aimed at
      enhancing the quality of life of women with HIV.

PMID- 14677214
TI  - The demand-control-support model and health among women and men in similar
      occupations.
AB  - The aim of the study was to investigate the main and the interaction effects of
      the demand-control-support (DCS) model on women's and men's health in a Swedish
      telecom company. According to the DCS model, work that is characterized by high
      demands, low decision latitude, and low support decreases health and well-being.
      Furthermore, control and support are assumed to interact in protecting against
      adverse health effects of stress. Earlier studies have failed to consider
      occupational status and gender simultaneously. Questionnaire data from 134 female
      and 145 male employees in similar occupations were collected. Correlational
      analysis supported the main effect hypotheses irrespective of gender.
      Hierarchical multiple regression analyses indicated that only demands predicted
      women's health, whereas both demands and lack of social support predicted men's
      health. However, no interaction effects were found for either women or men.
      Further studies should probe the relevance of the model while considering gender
      and occupational status.

PMID- 14677215
TI  - At jeopardy: the NIH as we know it.

PMID- 14677216
TI  - Standing balance and functional recovery of patients with right and left
      hemiparesis in the early stages of rehabilitation.
AB  - The objective was to determine the effects of the side of brain lesion on
      recovery of functional abilities and balance control among subjects 2 months
      following a stroke. There were 104 patients admitted consecutively to a geriatric
      rehabilitation center following their first stroke to the anterior brain
      circulation who were followed for 2 months. Fifteen age-matched individuals with
      no known impairments served as the control group. Functional ability was assessed
      with the Barthel Index and the Functional Ambulation Category. Posturographic
      testing was used to determine total sway and symmetry of weight distribution with
      eyes open and closed. Tests were performed 1 and 2 months poststroke. The results
      show that lesion side affects the recovery of independent stance 2 months
      following a stroke, with more patients with right hemiparesis able to reach this
      milestone. However, no difference was found in functional ability and balance
      control between patients with left and right hemiparesis who are able to stand
      independently by 1 month poststroke. Function and mobility improve during the 2nd
      month of rehabilitation (P = 0.001), but stance unsteadiness and asymmetry do
      not. The side of brain lesion seems to affect recovery of independent stance with
      an advantage to patients with right hemiparesis. However, there is no difference
      between balance control of individuals with left versus right hemiparesis in
      patients who reach independent stance by the end of the 1st month following their
      stroke.

PMID- 14677217
TI  - Home forced use in an outpatient rehabilitation program for adults with
      hemiplegia: a pilot study.
AB  - The objective of this study was to examine the effectiveness of a program of
      traditional outpatient neurological rehabilitation that included home forced use.
      In total, 17 patients with chronic stroke and 1 patient with subacute stroke
      (mean time poststroke = 27.6 months) completed an individualized program
      consisting of seven 2-hour treatment sessions composed of 1 hour of occupational
      therapy and 1 hour of physical therapy. Therapy sessions were completed over a 2-
      to 3-week period and included instruction on the use of a restraining mitt at
      home during functional activities. The Wolf Motor Function Test (WMFT) was used
      to assess upper extremity impairment and function at baseline, midway through
      treatment, and posttreatment. Patients demonstrated statistically significant
      improvements (P < 0.05 corrected for multiple comparisons) in mean time for
      completion in 12 of 17 WMFT subtasks when comparing baseline to posttreatment.
      The preliminary results suggest that the forced-use component of constraint
      induced therapy may be effective when applied within a traditional outpatient
      rehabilitation program. However, additional investigation is required to examine
      the effectiveness of using forced use within typical outpatient rehabilitation
      under more experimentally controlled conditions.

PMID- 14677218
TI  - Treatment interventions for the paretic upper limb of stroke survivors: a
      critical review.
AB  - Despite a threefold increase in treatment interventions studies during the past
      10 years, "best practice" for the rehabilitation of the paretic upper limb is
      still unclear. This review aims to lessen uncertainty in the management of the
      poststroke upper limb. Two separate searches of the scientific literature from
      1966-2001 yielded 333 articles. Three referees, using strict inclusion and
      exclusion criteria, selected 68 relevant references. Cohort studies, randomized
      control trials, and systematic reviews were critically appraised. Mean randomized
      control trial quality (n = 33) was 17.1/27 (SD = 5.2, 95% CI = 15.2-19.0, range =
      6-26). Mean quality of cohort studies (n = 29) was 11.8/27 (SD = 3.8, 95% CI =
      10.4-13.2, range = 4-19). Quantitative syntheses were done using the Z-statistic.
      This systematic review indicated that sensorimotor training; motor learning
      training that includes the use of imagery, electrical stimulation alone, or
      combined with biofeedback; and engaging the client in repetitive, novel tasks can
      be effective in reducing motor impairment after stroke. Furthermore, careful
      handling, electrical stimulation, movement with elevation, strapping, and the
      avoidance of overhead pulleys could effectively reduce or prevent pain in the
      paretic upper limb. Rehabilitation specialists can use this research synthesis to
      guide their selection of effective treatment techniques for persons with
      impairments after stroke.

PMID- 14677219
TI  - Income inequality and health: a critical review of the literature.
AB  - This article critically reviews published literature on the relationship between
      income inequality and health outcomes. Studies are systematically assessed in
      terms of design, data quality, measures, health outcomes, and covariates
      analyzed. At least 33 studies indicate a significant association between income
      inequality and health outcomes, while at least 12 studies do not find such an
      association. Inconsistencies include the following: (1) the model of health
      determinants is different in nearly every study, (2) income inequality measures
      and data are inconsistent, (3) studies are performed on different combinations of
      countries and/or states, (4) the time period in which studies are conducted is
      not consistent, and (5) health outcome measures differ. The relationship between
      income inequality and health is unclear. Future studies will require a more
      comprehensive model of health production that includes health system covariates,
      sufficient sample size, and adjustment for inconsistencies in income inequality
      data.

PMID- 14677220
TI  - Explaining racial differences in receipt of coronary angiography: the role of
      physician referral and physician specialty.
AB  - The authors examine three hypotheses regarding race differences in utilization of
      coronary angiography (CA): (1) patients with a cardiology consultation are more
      likely to obtain a referral for CA, (2) African American patients are less likely
      to have a cardiology consultation, and (3) among patients referred for CA, there
      is no difference by race in receipt of the procedure. To determine if they
      obtained a referral for or received CA, 2.623 candidates for CA were followed.
      Multivariate models were estimated using logistic regression. Cardiology
      consultation was associated with referral for CA (OR = 5.1, p < .001). White
      patients had higher odds of cardiology consultation (OR = 2.2, p < .001). The
      racial disparity was reduced among patients who received a referral (OR = 1.4, p
      < .05). Researchers must eliminate racial differences in access to specialty care
      and variation in referral patterns by physician specialty, and efforts must be
      targeted to those specialties where greater disparities exist.

PMID- 14677221
TI  - Hazards of hospitalization for ambulatory care sensitive conditions among older
      women: evidence of greater risks for African Americans and Hispanics.
AB  - Hospitalization for Ambulatory Care Sensitive conditions (ACSH) has been widely
      accepted as an indicator of the accessibility and overall performance of primary
      health care. Previous studies have found conflicting evidence about ACSH
      disparities associated with race or ethnicity for older persons. This study
      estimates discrete-time ACSH hazards for women aged 69 or older, using
      longitudinal data with multivariate controls. Data are from the 1984 to 1990
      Longitudinal Study of Aging, linked with Medicare claims. The multivariate
      results are adjusted for age, education, insurance and marital status, and other
      factors associated with health status and primary care access, and also for
      important indicators of need that include self-rated health, comorbidities,
      physical impairments, and previous hospitalizations. Many of these factors are
      permitted to vary across time for each individual, thus limiting measurement
      error. Results suggest that older African American and Hispanic women have
      markedly higher ACSH risks than older non-Hispanic white women.

PMID- 14677222
TI  - Hospital provision of uncompensated care and public program enrollment.
AB  - Hospital provision of uncompensated care is partly a function of insurance
      coverage of state populations. As states expand insurance coverage options and
      reduce the number of uninsured, hospital provision of uncompensated care should
      also decrease. Controlling for hospital characteristics and market factors, the
      authors estimate that increases in MinnesotaCare (a state-subsidized health
      insurance program for the working poor) enrollment resulted in a 5-year
      cumulative savings of $58.6 million in hospital uncompensated care costs. Efforts
      to evaluate access expansions should take into account the costs of the program
      and the savings associated with reductions in hospital uncompensated care.

PMID- 14677223
TI  - [Medical education--now evidence-based?].

PMID- 14677224
TI  - [Labor pain--a problem which should be solved].

PMID- 14677225
TI  - [Audit in obstetrics].

PMID- 14677226
TI  - [The effect of obstetric skills training with phantoms for physicians undergoing
      gynecologic-obstetric training].

PMID- 14677227
TI  - [New requirements for obstetric care].

PMID- 14677228
TI  - [Obstetric training--new methods].

PMID- 14677229
TI  - [Examination in gynecology and obstetrics for medical students. Time to change].

PMID- 14677230
TI  - [A study of labor pain experiences, knowledge of epidural pain relief and
      satisfaction with pain relief].

PMID- 14677231
TI  - [Should pregnant women at term with supposed ruptured membranes and unengaged
      fetal head be transported to the delivery room lying down?].

PMID- 14677232
TI  - [Pregnancy and diet. The importance of the diet during pregnancy seen from an
      epidemiological perspective].

PMID- 14677233
TI  - [Pregnancy and tobacco. A status article focusing on Danish conditions].

PMID- 14677234
TI  - [Alcohol during pregnancy: consumption, attitudes, information and tracing].

PMID- 14677235
TI  - [Pregnancy and caffeine].

PMID- 14677236
TI  - [Asthma in pregnant women].

PMID- 14677237
TI  - [Women and lung cancer--epidemiology, smoking and biology].

PMID- 14677238
TI  - [Anticholinergic treatment of overactive bladder. A costly treatment with
      doubtful clinical effect?].

PMID- 14677239
TI  - [Joint surgical aspects concerning the new surgical education seen with the eyes
      of a vascular surgeon].

PMID- 14677240
TI  - [Investigation of penicillin allergy].

PMID- 14677241
TI  - [Penicillin allergy].

PMID- 14677242
TI  - [Medical education at the university of Aalborg?].

PMID- 14677243
TI  - [Female dominance or necessary equality?].

PMID- 14677244
TI  - [Registration: how long shall we go?].

PMID- 14677246
TI  - [Medical terminology--again and again].

PMID- 14677245
TI  - [Scientific documentation of physical therapy].

PMID- 14677247
TI  - New survey findings. The reproductive revolution continues.

PMID- 14677248
TI  - LTC funding prospects brighten. Lender confidence is on the upswing, studies
      find.

PMID- 14677250
TI  - SNF survey revisited: management.

PMID- 14677249
TI  - Comfort, compassion, dignity mark end-of-life care.

PMID- 14677251
TI  - [Water for human consumption and health].
AB  - Providing enough water of good quality to all human communities is a difficult
      task, which has been satisfied only recently and only for the developed world. A
      large part of the developing world still suffers from scarcity and/or bad quality
      of water supply. Examples from the past are described, including the cholera
      epidemics of London 1848-1853 and the chromium pollution of the Milan area, 1958.
      A synthetic description of the different kinds of biological and chemical
      pollution are also described, then the complex mechanisms of biological and
      chemical pollution of the waters are illustrated, which require complicated
      interventions for reclamation after pollution or, better, even more complicated
      surveillance to avoid pollution. Finally the problem of safeguard of waters
      during the distribution is illustrated, when a bad maintenance of the aqueducts
      can inactivate all the precautions taken during the supply an the treatment of
      waters.

PMID- 14677252
TI  - [Strategic significance of water sources and risk management].
AB  - Water quality and its availability is a current and urgent issue. In fact, water
      is a unique natural resource, but its availability is limited. The paper presents
      data on its availability and usage. Its quality is of particular concern for
      safeguarding public health.

PMID- 14677253
TI  - [Water disinfection for human consumption: hygienic and health risks].
AB  - The present paper focuses on problems related to the disinfection treatments of
      drinking water also in the light of the latest regulations, the European
      Directive and the Italian decree acknowledge it. In this context, a critical
      assessment of the problem is included and future needs for research are proposed.

PMID- 14677254
TI  - [Diseases transmitted through water for human consumption].
AB  - The water for human consumption maintains a biological risk and can transmit
      diseases. The classical waterborne and the presently frequent diseases caused by
      protozoi Giardia and Cryptosporidium are considered and Arcobacter butzleri, a
      new waterborne pathogen, is described. Many measures have been adopted by
      institutions to ensure the quality of the drinking water. Managers and public
      health operators is working in order to verify the efficiency of more suitable
      indicators for its monitoring.

PMID- 14677255
TI  - [Virus transmission in drinking water].
AB  - Several epidemiological data confirm the presence of enteric viruses in drinking
      water. The present paper deals with several problems tied to the virological
      analysis, such as the concentration of the samples, the isolation and the
      identification of enteric viruses.

PMID- 14677256
TI  - [Potential relationship between microbiological indicators of contamination and
      emergent pathogens].
AB  - Emerging pathogens are defined as organisms that have increased in number within
      the past two decades or threaten to increase in the near future. A succession of
      emerging waterborne pathogens have been identified over the last 20 years but
      their significance to the water industry can take some time to establish. This
      paper will discuss organisms of potential concern and their possible
      relationships with the traditional bacterial indicators of faecal contamination.

PMID- 14677257
TI  - [Water procurement at food production/processing facilities].
AB  - Water supplies in food industries need to respect particular hygienic
      requirements. The present paper describes the requirement and the characteristics
      of water to be used in food industry. Water quality for the hygienic procedures
      is very important and specific requirements in this context are reported.

PMID- 14677258
TI  - [Water as risk factor for helminthiasis in domestic ruminants in the central and
      southern Italy and zoonotic risk].
AB  - The findings of recent epidemiological surveys regarding the distribution of
      helminths in sheep, cattle, and buffaloes in central and southern Italy show that
      the presence of water in breeding, such as streams, canals, brooks, rivers and
      lakes, is a risk factor for the following helminths, agents of emerging zoonosis:
      Fasciola hepatica, Dicrocoelium dendriticum, Trichostrongylus spp., Ostertagia
      spp., Nematodirus spp., Haemonchus spp., Bunostomum spp., and Oesophagostomum
      spp. The Authors report up-to-date data on the distribution of the above cited
      helminths, as well as their essential morphological and biological
      characteristics and their zoonotic role.

PMID- 14677260
TI  - [Groundwater and spring water in the area of Cassino].
AB  - The historical evolution and the hydro-geologic characteristic of the area of
      Cassino are described. The great availability of water in this area deserves much
      concern and needs a better utilizing as regards its hydro-geologic equilibrium
      and its environmental protection.

PMID- 14677259
TI  - [Future development of the "integrated water cycle"].
AB  - In this presentation problems connected to the usage and management of entire
      water cycle are illustrated. The solution has to be found in a reorganization of
      the national water system. When the regulation n. 36/94 (legge Galli) will be
      completely in force, an improvement of the efficiency of the entire organization
      of the integrated water cycle will be obtained.

PMID- 14677261
TI  - [Treatment of surface water].
AB  - The present paper describes the most important treatment processes to be used for
      water for human consumption. Advantages and disadvantages of alternative
      disinfectants are discussed and a critical assessment of the problem associated
      to disinfection byproducts is included.

PMID- 14677262
TI  - [Main Italian aqueducts: the aqueduct of western Campania].
AB  - EniAcqua Campania, as concessionary of the Campania Region, manages the aqueduct
      of the western Campania. The characteristics, the water flow, the water works of
      the aqueduct are briefly described. After completion, it will supply water to 70
      municipalities for up to about 3,000,000 inhabitants and vacationers.

PMID- 14677263
TI  - [Systematic study of microbiological and parasitological quality of drinking
      water: the example of Cassino].
AB  - In order to evaluate microbial and parasitological quality of water resources
      located in the area of Cassino, different typologies of water were monitored
      during the course of 2002. Analytical results showed that neither water sources
      nor chlorinated water were affected by microbial and parasitological
      contamination. Surface water can be used as drinking water after suitable
      treatment processes. The constant occurrence of parasitic protozoa in sewage
      shows their spreading in the environment; nevertheless their absence in
      groundwater and tap water suggests a good level of hygienic quality in water
      management.

PMID- 14677264
TI  - [Preliminary study of the chemical characteristics of water inside and outside
      the area of Cassino].
AB  - Quality and control of waters, particularly phreatic waters, is a strong need of
      a modern society and in particular of all administrations that is entitled to
      care for its citizen's health. The current legislation although not very strict,
      or at least not as strict and careful as it should be and definitely less than
      that of the World Health Organization (WHO), has recently constrained thresholds
      for maximum concentrations of chemical species dissolved into waters (anions,
      cations and heavy metals). Comparisons between data from water analyses collected
      in Cassino area and these thresholds have shown that these waters resulted of
      very good quality and they are not related to any source of inorganic pollution.
      Tap water should be preferred to mineral water usually in stores. Economically
      they are at least one thousands times cheaper and often can be considered of
      better quality.

PMID- 14677265
TI  - [The ancient Terme Varroniane at Cassino].
AB  - In the paper the history of the Terme Varroniane is presented. This historical
      and pleasant site is situated near Cassino. The location is described and the
      characteristics and beneficial effects of its low in mineral content water are
      reported.

PMID- 14677266
TI  - Calcium concentration at rat females with osteoporosis after applying calcium
      fumarate.
AB  - The dynamics of total calcium concentration in blood of rat females with
      osteoporosis caused experimentally after applying it in the form of fumarate was
      determined. The fumarate was applied in just one dose by the means of stomach
      tube at the dose of teoporoz_ 4.28 mg of calcium/100 g of body mass. The total
      calcium concentration in blood was determined: 0; 1; 2; 3; 5 i 7 h after
      application. It was observed that one hour after application calcium
      concentration in control group increased by 19.3%, and in the group of animals
      after ovariectomy it decreased by 6.7% (P < 0.001). After 2 h calcium
      concentration in both groups returned to its initial state, and after 3 hours
      three next decrease in relation to initial time by 10% occurred in the control
      group and by 4% in the group after ovariectomy. Between 4 h and 7 h after
      administration calcium concentration in both groups of animals was even and it
      was maintaining at the constant level in the range 2.248-2.172 mM/l.

PMID- 14677267
TI  - Is the pharmaceutical market in Bulgaria innovative?
AB  - After the turn to market oriented economy a lot of drugs were authorized for sale
      in the East European countries. Because of the limited resources of these
      countries, mainly generic or brand generic products were licensed. The number of
      the patented drugs on the market could be used as measure of the market
      attractiveness to the R&D producers. The study shows the analysis of the
      innovativeness of the Bulgarian drug market comparing the registration and the
      patient activity of the producers. The number of the authorized products for five
      years period (1990-2000) and share of the patented products were investigated.
      During the observed period the number of newly authorized pharmaceuticals
      increased almost seven times from 800 (650 INN) to 6000 (2000 INN) dosage forms.
      The prevailing part of the newly registered drugs was found to be brand generics
      and possess only trade name protection. The share of drugs that are patented is
      less than five percent of all newly registered medicines, and among the fifty
      most commonly prescribed and sold medicines between 1996-2000, only 0.5 percent
      of drugs were patented. Obviously the Bulgarian pharmaceutical market is very
      competitive but not that attractive for most of the R&D producers. In general the
      registration of the patent protected products is increasing during the years and
      especially after harmonization of the related legislation with the EU
      requirements. The patent activity of the pharmaceutical companies regarding newly
      authorized drugs is influenced by the structure of morbidity and population.
      During the last two years the patent activity is increasing and is oriented
      mainly towards the protection of newly authorized drugs or pharmaceutical forms
      and obligatory registration of trademarks for the privatized Bulgarian
      pharmaceutical manufacturers.

PMID- 14677268
TI  - O/w dispersions development containing liquid crystals.
AB  - Liquid crystals are defined as the intermediary state between solid and liquid
      and also called of mesomorphous phase or crystalline phase, presenting
      characteristics of the mentioned physical states. For the simple emulsions that
      intermediary phase can act as forms of encapsulation of drugs providing its
      controlled liberation and besides, it can increase cutaneous hydration. These
      characteristics evidences the differentiation of the developed formulations and
      the use of the same ones in the release of new cosmetic vehicles. In that
      research we use vegetable oils (coffee, tomato), mineral oil, surfactants like
      phosphorics esthers (fractions A and B) and distilled water as aqueous phase. The
      stable formulations were submitted to stability physic-chemical preliminary tests
      (pH values determination, electric conductivity values, centrifugation and
      thermal stress) and later the compositions were submitted to accelerated
      stability tests (cold-hot cycle in the following temperature conditions--4 +/- 2
      degrees C, 25 +/- 2 degrees C and 45 +/- 2 degrees C). Crystalline phase was
      identified by microscopy polarization. The recently prepared formulations and
      aged formulations (after 30 days) were appraised for rheology.

PMID- 14677269
TI  - Microbiological quality of vegetable drugs commercialized in open-air markets for
      use in infusion preparations according to the part of the vegetable used.
AB  - The microbiological quality of different parts of vegetable drugs, commercialized
      in an open-air market, and intended for use as infusion preparations was
      compared. Total viable aerobic microorganisms, fungi, total and fecal coliforms
      and Enterobacteriaceae counts demonstrated lower sanitary quality in drugs
      composed of roots than those composed of leaves and caulis. E. coli was
      identified in some samples, but all of them were free from Salmonella sp.

PMID- 14677270
TI  - What is the scope of bioluminiscence in pharmaceutical clean rooms monitoring?
AB  - By means of bioluminiscence ATP present in a sample can be quantified. Thus, it
      would be a method able to evaluate microbiological or organic matter (from
      vegetal or animal origin) contamination. The present work analyzes the
      possibility to assess--from the microbiological point of view--the air of
      pharmaceutical clean rooms by means of bioluminiscence, using the luminomiter HY
      LITE 2 [Merck]. It is thought that the use of this methodology versus
      microbiological classical methods, will allow to obtain results in the working
      day. Classical methods demand a minimum of 72 hs incubation to read results. But
      the real conclusion is that with the used technology, it is not possible to
      evaluate microbiologically the air of pharmaceutical clean rooms.

PMID- 14677271
TI  - Stability studies of tablets containing 5 mg of policosanol.
AB  - The stability studies of tablets containing 5 mg of policosanol, a new
      cholesterol lowering drug, were conducted to predict an expiration date and to
      search the appearance of putative degradation products. All quality parameters
      such as colour, moisture content, hardness, disintegration, policosanol content
      and microbiological limits of the tablets were assessed. The effect of extreme
      treatments such as acid and basic hydrolysis, oxidative and photolytic
      degradation as well as thermal degradation, on the policosanol content was
      studied. In addition, studies under extreme conditions of storage [(40 +/- 2)
      degree C and (75 +/- 5)% R.H.] as well as 37, 45, 55 and 60 degrees C combined
      with 50, 75 and 92% R.H.) and under ambient conditions of storage for climatic
      zones II and IV were performed. These studies demonstrate that these tablets are
      a stable pharmaceutical formulation, without significant changes in their quality
      criteria at the stressed conditions used, so that policosanol content remains
      unchanged during the entire studies. The chromatographic profile of the samples
      after 9 months of thermal degradation shows chromatographic peaks that
      corresponds to the palmitate and stearate esters of octacosanoyl, triacontanoyl
      and hexacosanoyl, being the only degradation products observed on these studies.

PMID- 14677272
TI  - Intra-gastric performance and bioavailability study of a new per-oral bioadhesive
      Verapamil HCl matrix tablet in dogs.
AB  - In a previous study, we developed a per-oral extended--release bioadhesive matrix
      tablet for verapamil HCl (VP). The system combined both strong bioadhesion and
      sustained release properties in vitro. The purpose of this study is to evaluate
      the in vivo performance of the prepared bioadhesive tablets (B). The conduction
      of a periodic X-ray imaging of the abdomen of beagle dogs, after administration
      of B containing 12% barium sulfate, was used to evaluate the intra-gastric
      performance. The VP concentrations in blood samples taken at specified times
      after oral administration of B to fasted beagle dogs were determined and compared
      with those obtained after administration of a commercial sustained release VP
      tablets (Manidon 120 R). The X-ray images showed that bioadhesive tablets
      remained almost at the same place in the stomach for at least 6 hours while it
      disappeared after 1 hour in case of the control tablets. No statistical
      difference was seen between the Cmax, tmax, AUC, t1/2, and MRT for B compared to
      Manidon. The Cmax was found to be 51.4 +/- 15.5 and 48.6 +/- 17.9 (ng/ml) for
      Manidon and B, respectively and the corresponding tmax were 7.0 +/- 1.9 and 6.0
      +/- 0, respectively. The AUCO-. for Manidon and B were 949.84 +/- 245.11 and
      722.92 +/- 144.42 ng.h/ml, respectively. So, the prepared B tablets can be
      considered bioequivalent to the commercial Manidon Retard product.

PMID- 14677273
TI  - Pellet coating by air suspension technique using a mini-model coating unit.
AB  - Air suspension coating is widely used in the pharmaceutical industry, as an
      attractive alternative to pan coating in that it can successfully coat small
      particles, pellets and tablets irrespective of size or shape with a wide variety
      of coating materials. The commercially available air suspension coating
      equipments require at least one kilogram of material for optimum efficiency of
      their working. Therefore, it is felt that there is a potential need for a small,
      compact air suspension coating instrument, which can work with gram quantities of
      material. The main objective of the present work is to design and evaluate a
      laboratory model top spray air suspension coating instrument. The performance of
      the instrument was evaluated for both, drug loading on to non-pareil pellets and
      coating of drug-loaded pellets. Terbutaline sulphate was selected as model drug,
      while Surelease (aqueous polymeric dispersion of ethyl cellulose) as
      representative coating material. The drug loading efficiency of the instrument
      was found to be around 82% with a pellet load of 10 g. The drug loading
      efficiency was found to be satisfactory and reproducible. Scanning electron
      micrographs of coated pellets indicated that coating was homogenous and uniform
      around the pellets. The maximum deviations observed in the in vitro drug release
      studies were +/- 2.7397% of the mean percent quantity of drug released, which is
      low enough for the coating to be considered uniform and reproducible.
      Reproducibility of the coating process was further confirmed by determining the
      95% confidence interval for average difference in cumulative percentage drug
      release between two runs of each batch, which was found to be less than 5% set as
      the maximum allowable difference. The release data obtained were found to show
      best fit with first order kinetic model. A significant influence of coating
      thickness on the drug release rate was observed. From the results and
      observations of this work, it may be concluded that the mini-model air suspension
      coating instrument designed, may be a useful piece of equipment for preparing
      coated multiparticulate dosage forms in small quantities for sustained drug
      delivery, especially in research works.

PMID- 14677274
TI  - Comparison between polarography and titrimetry methods for determination of
      ascorbic acid in pharmaceutical dosage forms.
AB  - In view of the widespread use of vitamin C several methods were developed for the
      determination of vitamin C in pharmaceutical preparation. Titrimetric and
      colorimetric methods commonly used to assay ascorbic acid. Unfortunately these
      methods have some failures regarding manipulative steps. Ascorbic acid oxidizes
      at DME and it can be a specific way with fewer steps in sample preparation in
      order to assay vitamin C. In this study a polarographic method was performed to
      determine ascorbic acid in several pharmaceutical dosage forms. The samples were
      prepared in oxalic acid solution and a standard addition method was performed
      during the experiments. The method has comparable precision compared with common
      method and it is even gave less error percent. Polarographic assay also is faster
      and easier to perform and could be used for routine determination.

PMID- 14677275
TI  - Release of indomethacin from bioadhesive tablets containing carbopol 941 modified
      with Abelmuschus esculentus (okra) gum.
AB  - Carbopol 941 (C-941) and Abelmuschus esculentus gum (Okra gum, AEG) were used as
      bioadhesive polymers in the formulation of mucoadhesive indomethacin tablets.
      Different batches of the tablet compacts were formulated based on different
      combination ratios of the polymers. The bioadhesive properties of the tablets
      were studied using a tensiometer: Tablets coated with 50% w/v solution of
      Eudragit I. 100 in ethanol, were also prepared and evaluated. The following
      tablet physical properties were evaluated: hardness, uniformity of weight,
      disintegration time, friability, and absolute drug content. Release studies were
      determined in simulated intestinal fluid (SIF pH 7.2) without pancreatin, and in
      0.1 N solution of HCl. Result obtained indicated that tablets with equal ratio of
      C-941 and AEG (1:1) gave the highest bioadhesive strength for both the coated and
      uncoated tablets. The percentage of drug released ranged from 53-90% for uncoated
      tablets in 0.1 N HCl and SIF, and 9-16% for coated tablets in 0.1 N HCl, and 63
      100% for coated tablets in SIF after 8 hrs.

PMID- 14677276
TI  - [Surgical risk in the elderly].
AB  - In our Country 16% of population is over 65 years old and on 2010 a quarter of
      people will be over 70 years old. More over the percentage of patients over 70
      years admitted in surgical departments is triple than 10 years ago and the
      percentage of octgenarian patients is ten times. In the last years new methods of
      diagnosis and care have been introduced to reduce morbility and mortality; the
      preoperative evaluation to define the risk factors is complex. The surgeon should
      respect some primary points: the patient interest, true surgical treatments,
      multimodal management, valid pain therapy, discharge as soon as possible,
      ambulatory or day hospital management, expecting and quality of life.

PMID- 14677277
TI  - [The role of palliation in peri-ampullar tumors in the elderly].
AB  - Authors wonder about the actual part of the palliative practices in periampullar
      cancers of the geriatric age, and the choice criteria of the different surgical
      options that are practicable. They reaffirm that the common radical operation is
      the pancreaticoduodenectomy, even if, as it is verifiable in the relevant
      literature and in our series of cases, it is practicable only a few times. The
      necessity of amending the toxic-septic condition of the neoplastic cholestasis,
      which certainly is more unfavourable during the geriatric age, gives to the
      palliative procedures a better role, because few patients could be treated with a
      curative intention. Authors report their experience and their results about the
      icterus regression, mortality, morbidity and the average survival rate. About the
      surgical palliative options of the bilio-digestive shunts, they give the same
      importance to the gallbladder jejunostomy and to the common bile duct
      jejunostomy, granting to the first their preference in the geriatric age for the
      simplest and rapid execution. They point out the necessity of the
      gastrojejunostomy in all the present or incipient jejuno's obstruction, because
      of the surgical action importance, and to avoid another operation. They give,
      even in the geriatric age, their preference to the surgical palliative
      treatments, proposing to reserve the endoscopic and radiologic practices to the
      patient undergoing an operation for the precarious general state, for the high
      operating risk and the modest residual life. In fact, the non surgical treatments
      are suitable to amend the neoplastic cholestasis, but they aren't equivalent to
      the surgical palliative, that is more effective for the greater survivals, a
      better life's quality, a smaller mortality and morbidity.

PMID- 14677278
TI  - [Intestinal infarction in the elderly].
AB  - The bowel infarction is till affected by high mortality in spite of new
      diagnostic methods and therapy. In our experience was observed about 45 patients
      with bowel infarction by different etiology; fast diagnosis and therapy are
      necessary for a good prognosis. The arteriography, at the light of this
      experience, is the gold standard but it is still performed in a low number of
      patients. The laparoscopy, in the advanced pathologies, is able to avoid an
      ineffectual laparotomy and permits a better diagnosis in borderline cases.

PMID- 14677279
TI  - [Septic shock: surgical and medical problems in the elderly].
AB  - The sepsis is a bacterial invasion of the organism producing many manifestations
      which are able to amplify themselves. In the United States of America there are
      100,000 death per year and the incidence is among 300,000-500,000 cases. The
      major surgery in the elder (especially if it is in emergency) has a great
      percental of risk because the preoperative study isn't often complete. Fever,
      agitation, panting, bullation, abdominal splinting, enteroplegia, are signals of
      evolving inflammatory situation. Moreover there are disorders of biochemical
      values: leukocytosis, thrombocytopenia, increased levels of VES, PCR, amylase and
      biliribinaemia. The more common radiological examinations are the straight
      radiography of abdomen and horax, abdomen ultrasonography, CT or MRI. In the last
      years pro-calcitonin, interleukin-6 , C-reactive protein, and nitric oxide from
      endothelial and muscularis cells have been evaluated as prognostic factors in the
      septic shock.

PMID- 14677280
TI  - [Treatment of the early form of rectal carcinoma in the elderly].
AB  - The early rectal cancer which needs conservative surgical treatment should
      present some pathological characters: intramucosal site without muscularis
      invasion (pT1), high or moderate differentiated grading (GI-G2), no lymph node
      metastasis or vascular invasion. Total mesorectal excision is the gold standard
      for these neoplasms and permits very low resection or colo-anal anastomosis with
      sphincter function preserving. However, this type of surgery has still a high
      percentage of postoperative morbidity and mortality (some authors report
      respectively 40% and 5%). Therefore the local excision in selected cases is able
      to preserve the sphincter function and to reduce the postoperative complications
      with high probability of recovery.

PMID- 14677281
TI  - [Therapeutic strategy in neoplasia of the pancreas and ampulla].
AB  - The major symptoms of periampullary neoplasia are jaundice, lowering of weight,
      abdominal pain extending behind; diabetes, pancreatitis or exocrine pancreatic
      failure are uncommon. In the last years, surgery has been considered as the gold
      standard of the therapy because new technologies are able to reduce morbility and
      mortality. In the too advanced neoplasia, palliative surgical care permits better
      survival and quality of life. The duodenopancreatectomy today has a low
      perioperative mortality (0-3%) and an acceptable survival (15.25%). Good results
      were found for palliative surgery in unresectable neoplasms while in the
      inoperable patients we consider endoscopic and radiological treatments better
      than chemotherapy because they are able to correct the jaundice, improving
      quality of life (but not survival).

PMID- 14677282
TI  - [Breast cancer in advanced age].
AB  - The incidence of breast carcinoma increases with advancing age. In view of the
      progressive aging of the population, this problem will tend to become more and
      more frequent. At present, patients of advanced age are often "undertreated"
      owing to the mistaken prejudice that older patients are unable to withstand
      standard multimodal therapy for this disease. In fact, there is no scientific
      evidence to that effect. Treatment choices should therefore be largely comparable
      to those adopted in younger patients. Even chemotherapy, which encounters the
      strongest resistance, by patients but also by doctors, should be administered
      when indicated. A number of studies have demonstrated that the toxic and side
      effects observed in elderly patients are comparable to those observed in younger
      age groups. In practice, particular attention needs to be paid when administering
      cytostatic treatment to patients over 80 years of age. Very conservative
      treatment (tamoxifen plus radiotherapy) may be reserved only to particularly
      frail elderly patients. In conclusion, the therapeutic choice should depend more
      on assessment of the biological age, life expectancy and patient's expectations
      than on the anagraphic age.

PMID- 14677283
TI  - [Management of thoracic and thoraco-abdominal aneurysms in the elderly].
AB  - Repair of descending thoracic aneurysm or thoracoabdominal involves transient
      ischaemia of many organs with high risk of complications. The elderly patient may
      be more at risk depending on the presence or absence of significant comorbidity
      factors. Careful preoperative evaluation and patient selection considerably
      reduce the risk of operative mortality and morbidity. We review the management of
      thoracic and thoracoabdominal aneurysms in the elderly and briefly describe our
      surgical approach in order to minimize operative risk and improve surgical
      results.

PMID- 14677284
TI  - [Carotid endarterectomy in the elderly].
AB  - The elderly population has the highest risk for developing stroke and the annual
      death rate is some 394/100,000 population. Moreover, the elderly are the fastest
      growing segment in our society. In carefully selected patients carotid
      endarterectomy may provide to prophylaxis against stroke. With a careful
      selection, acceptable low operative motality and morbidity rates may be achieved,
      comparable to the 4.3% and the 2.3% of the Veterans Affair and ACAS studies, in
      which the patients' mean ages were 64.1 and 67 years respectively.

PMID- 14677285
TI  - [Endovascular treatment of aneurysms in the elderly].
AB  - The constant increase in the median age over 80 requires more and more care from
      vascular surgeons to obtain better results in the treatment of aortic
      degenerative diseases. In the last years a remarkable improvement in the
      procedures of endovascular surgery of abdominal aortic aneurysms has been
      reached. Actually different prostheses are available for the treatment of aortic
      aneurysms. The early results of these procedures are similar to the traditional
      surgical techniques, but at the moment long term results are not yet available.
      The Authors underline the importance of a long term follow up to allow a correct
      evaluation of physiopathological modifications in the aortic circulation.

PMID- 14677286
TI  - [Lung resection in the elderly: some limits].
AB  - INTRODUCTION: A progressive and constant increase of mean life duration in the
      last century has determined the challenge of the treatment of lung cancer even in
      the elderly with good functional status. The aim of the present study is to
      evaluate the results obtained in the elderly, over seventy years old, who
      underwent pulmonary resection at our Division of Thoracic Surgery of Polyclinic
      of Bari from 1985 to 1995. PATIENTS AND METHODS: 938 patients with NSCLC have
      been operated on, from January 1985 to December 1995. 189 were over seventy and
      19 were over eighty years old. We have performed the following surgical
      procedures: 21 pneumonectomies, 108 lobectomies/bi-lobectomies, 44 wedge
      resections, 16 staging thoracotomies. RESULTS: Post-operative complications were
      as follows: atelectasis 57, air leak 37, empyema 9, broncho-pleural fistula 3,
      arrhythmia 103, pulmonary edema 8, cardiac ischemia 3, pulmonary embolisms 1,
      delirium 2, hemothorax 3, exitus 5. There were 3 deaths caused by acute
      myocardial ischemia, one by pulmonary embolism, one by main right bronchus
      broncho-pleural fistula. Two and five-year overall survival were 67.1 and 37.8,
      respectively. CONCLUSION: Diagnostic and therapeutical procedures for lung cancer
      should be different in the elderly. In our experience, main post-operative
      complications were cardiovascular, consequent to the entity and duration of
      surgical operation and intra-operative blood leaks. The elderly require a more
      careful post-operative monitoring to prevent this kind of complications.

PMID- 14677287
TI  - [Minimally invasive thoracic surgery versus standard surgery].
AB  - Advances in technology, with the availability of optics and minitelevision
      cameras and improved endoscopic instrumentation (especially endo-stapler
      devices), have allowed the surgeon to obtain a superior panoramic view of the
      thoracic cavity and an optimal surgical manuvrability. This has determined the
      development, besides the traditional thoracotomic approach, of minimally invasive
      techniques of video-assisted thoracic surgery (VATS). An auxiliary mini
      thoracotomic approach and the magnification of the operating theatre, which
      allows the surgeon to accomplish difficult manoeuvres under diret view, have
      progressively extended the indications of this procedure: at first used for the
      treatment of pneumothorax and pleural effusions, it is now employed in biopsy or
      atypical resection of pulmonary nodules, lung cancer staging and diagnostic
      therapeutical procedures of mediastinal diseases, major pulmonary resections
      (lobectomy and pneumonectomy) and lung volume reduction surgery for emphysema
      (LVRS). The Authors review minimally invasive techniques of video-assisted
      thoracic surgery (VATS), compared to the traditional surgical ones, for the
      treatment of various thoracic diseases.

PMID- 14677288
TI  - [Surgical strategy in the treatment of adrenal cortex cancer. Expanded and
      repeated interventions].
AB  - AIM OF THE STUDY: To analyze our patients affected by adreno-cortical carcinoma
      (ACC) considering in particular the therapeutical approach in case of local
      recurrence or metastasis, and to compare our results with those from literature.
      PATIENTS AND METHODS: Since 1975 up to 2001, 35 patients with ACC were observed,
      27 female and 8 male, aged between 3 and 76 year. All patients were surgically
      treated, 3 out of which laparoscopically. Thirty patients underwent radical and 5
      palliative surgery. Twenty-two patients had extended resections to surrounding
      infiltrated organs, such as spleen, pancreatic taIl, vena cava, left colon and
      liver. The intervention was always completed by regional lymphadenectomy.
      Adjuvant treatment was administered in 17 patients, 4 out of which were re
      operated. RESULTS: Only one patient died in the perioperative period for
      hyperacute adrenal failure. The survival rate was 85.7% at one year, 76.5% at two
      years, 70.8% at three and 28.3% at five years. Out of the 30 patients radically
      treated, only 3 are disease-free up to now. Local recurrence or metastatic
      disease was observed in 27 patients, out of which only 9 were eventually
      surgically treated, once or more times. All non-operated patients died between 1
      and 6 months from the recurrence. The survival rate of the 9 re-operated patients
      was 51% at 2 years, and 22.1% at 5 years. Interestingly, one patient who has been
      re-operated three times, is still alive and disease-free after 7 years from the
      first recurrence. No significant difference was observed between Mitotane-treated
      and non-treated patients. CONCLUSIONS: According with data from literature, we
      conclude that surgical therapy of recurring local or metastatic ACC is up to now
      the best treatment, independently from the original stage of the disease.
      Controversies still remain about the utility of adjuvant chemotherapy in the
      primary and the recurrent disease.

PMID- 14677289
TI  - Surgical treatment of inflammatory bowel diseases in northwestern Italy: a
      multicentric study by the G.S.M.I.I. (Inflammatory Bowel Disease Study Group).
AB  - BACKGROUND AND AIMS: Improved medical therapy and bowel sparing and sphincter
      saving techniques have changed surgery for UC and CD. Collaboration between
      gastroenterologists and surgeons is necessary to uniform the indications for
      surgical treatment reducing emergency operations. GISMII multicentric study aimed
      to show indications, timing and impact of surgery, through retrospective analysis
      of cases observed between 1992 to 1996. METHODS: Data were obtained by 16
      departments of General Surgery. RESULTS: 102 UC and 376 CD patients were
      analyzed. In UC patients surgery was performed for failure of medical therapy in
      54%, complications in 28.4%, cancer or dysplasia in 10% of cases, 83.3% elective
      procedures. 30.4% ileo-anal pouch, 30.4% total procto-colectomies with definitive
      ileostomies, 32.4% total colectomies with ileo-rectal anastomosis, 6.8% segmental
      resections, were performed. In CD patients surgery was performed in 21% for
      medical therapy failure, in 79% for complications. 53.4% of patients were
      submitted to 1 operation, 84% elective procedures. Reoperations were performed in
      46.6% of patients, 70.3% elective procedures. In the first operation bowel
      resection was performed in 79.1%, stricturoplasty in 14.3%; in the subsequent
      operations bowel resection 62.8%, stricturoplasty 21.7%, increasing number of
      temporary or definitive ileo-stomies. CONCLUSIONS: Collaboration between
      gastroenterologists and surgeons is necessary to obtain optimal results, reducing
      the incidence of emergency surgery, and complications. The short period observed
      between diagnosis and operation (21.4 months) is due to the increasing tendency
      of gastroenterologists to anticipate a surgical procedure when young patients
      with a chronic disease need a prolonged medical therapy.

PMID- 14677290
TI  - [Complicated colon cancer: the experience at an Operative Surgery Unit].
AB  - INTRODUCTION: Prognosis of colon cancer is worse if complications are present at
      the moment of diagnosis. The high mortality rate with surgery in emergency in
      such cases needs a careful reflection about the best suitable operation to
      perform. MATERIALS AND METHODS: 107 consecutive patients observed along a 9 year
      period for colon-rectal cancer are retrospectively analysed. 27 of them were
      complicated at the presentation for obstruction (19 patients), colon perforation
      (6 patients) or rectal hemorrhage (2 patients). In the whole experience 5
      patients underwent primary resection of the tumour and direct anastomosis; 5 only
      a decompressive colostomy; 6 were primarily resected and anastomized under the
      protection of a cecostomy; 6 other patients underwent a Hartmann procedure; 2
      were treated with only an intestinal by-pass; 1 was treated with Miles procedure;
      1 with an anterior rectal section and the last one was resected-anastomosed in
      two steps, after a temporary decompressive colostomy. RESULTS: Intraoperative
      mortality was of 11.1% (3 patients) and morbidity 18.5% (5 patients). General 5
      years survival was 62.1% among the cases complicated at presentation. The
      recurrence rate was 8.45%. Both these figures are below a statistical
      significance (p = 0.57). CONCLUSIONS: The necessity to treat in emergency the
      colon cancers reduces the possibility to adopt the best rules of modern
      programmed oncologic surgery giving up the chemotherapy w/o neoadjuvant
      radiotherapy with which a preoperative down-staging of the tumour were possible.
      For these reasons in emergency not only mortality and morbidity are higher than
      in case of elective surgery, but also metastasization and recurrence are worse
      because of a more difficult radicality in surgery.

PMID- 14677291
TI  - [Paraesophageal hiatal hernia. Clinical considerations and report of a case].
AB  - OBJECTIVE: The authors report their experience about the treatment about a case
      of paraesophageal hernia and they redefine nosography. DESIGN: Report of 1 case;
      evaluation of effectiveness of surgical treatment. 1-year follow up. Review of
      its clinical presentation. SETTING: Operative Unit of General and Thoracic
      Surgery. Department of General Surgery, Emergency and Transplantation. Polyclinc,
      University of Palermo. INTERVENTION: The patient was submitted to surgery with
      radical and curative intention. RESULTS: Complete resolution of the pathology.
      Follow-up (1 year) negative. CONCLUSION: Management of patients affected by
      paraesophageal hernia is difficult, because the physiopathology, anatomic basis
      and clinical presentation are not yet clear. The aim of surgical treatment is to
      reduce the hernia, to repair the hiatal gap and to make a correct antireflux
      procedure. According to us, the open surgical approach is very safe and useful
      because allows more safe surgical dissection, even if there is a big scar on the
      abdomen, the postoperative staying in hospital is longer. Finally, we emphasise
      the role of follow-up in these patients: it's the only way to prevent
      complications.

PMID- 14677292
TI  - [Encapsulating sclerosing peritonitis: report of 2 cases].
AB  - SEP is an increasingly seen complication of CAPD; we have the occasion to see
      again this condition because two patients came under our observation. We have
      remarked the unknown etiology and pathogenesis, the difficult diagnosis and
      therapy, and the often poor prognosis.

PMID- 14677294
TI  - Prevention of cervical cancer in Africa: a daunting task?
AB  - Africa has a high estimated incidence of cervical cancer, thus requiring the
      development of an effective prevention strategy. Cytology-based screening is
      beyond the capacity of many African countries, hence the need for alternatives.
      Visual inspection of the cervix after application of 3-5% acetic acid (VIA) is a
      promising screening test, with similar sensitivity to that of cytology but lower
      specificity. The same accounts for other VIA methods using magnification devices,
      visual inspection after the application of Lugol's iodine, or human papilloma
      virus (HPV) DNA testing, all proposed alternatives to cervical cancer prevention
      screening tests. Vaccination against HPV is the most promising strategy for the
      prevention of cervical cancer, but a wider variety of HPV types than currently
      being investigated must be considered for the development of the multivalent
      vaccine preparations required in Africa. Other considerations in developing an
      effective prevention programme include full public sector investment and
      achieving acceptability of a vaccine against a sexually transmitted infection
      targeted for adolescents. Unfortunately, however, if HPV vaccines are developed
      the initial impact of prophylactic vaccines will be delayed for many years.
      Alternative strategies should, therefore, be promoted in parallel. There are
      several approaches to cervical cancer prevention and their evaluation should be
      comprehensive and coordinated to achieve short and long-term public health
      benefits in different programme settings.

PMID- 14677293
TI  - Perforation of a ureteral diverticulum: a case report and review of the
      literature.
AB  - The ureteral diverticulum represents a rare pathology. It is infrequently
      symptomatic and even more infrequently it manifests itself as an acute event. To
      our knowledge this is the only case described in the literature of perforated
      ureteral diverticulum with consequent uroperitoneum.

PMID- 14677295
TI  - Dual protection against sexually transmitted infections and pregnancy in South
      Africa.
AB  - Promotion of simultaneous protection against sexually transmitted infections
      (STIs) and unintended pregnancy, referred to as dual protection, represents an
      important public health intervention. We investigated its prevalence and
      correlates in South Africa. A cross-sectional survey of 929 sexually active
      women, aged 15-49 years, was conducted in 89 public primary health care clinics,
      with dual method use and use of condom alone at last sexual intercourse as
      outcomes. At last intercourse, 12% of women were protected from both STIs and
      pregnancy. In multivariate analysis, higher education, being unmarried, and
      multiple sex partnership in the past year were predictors of dual method use,
      while younger age, higher education and awareness of the dual function of condoms
      were predictors of condom use alone. Dual protection is low in this population.
      The predominance of hormonal contraceptive use in South Africa means that
      increasing barrier method use among hormonal contraceptive users is an important
      strategy for increasing dual protection.

PMID- 14677296
TI  - The Norplant experience in Zaria: a ten-year review.
AB  - Norplant is an effective, long-acting, reversible, progestin-only contraceptive
      that provides protection for up to five years. The aim of this review is to
      ascertain the response of family planning clients in Zaria to Norplant. In
      Nigeria, Family Health International started pre-introductory clinical research
      on Norplant in 1985 at five sites including Zaria. Since the conclusion of the
      study, Norplant services have been maintained, but no attempt has been made to
      report the response of this largely Hausa and Muslim community where
      contraceptive use is generally low. It is important to determine whether the
      advantages of Norplant have had an impact on this setting. The study showed that
      most of the clients were satisfied with the method. There was a progressive
      increase in the number of women using Norplant by 1995, with a significant
      decrease in the number of women undergoing sterilisation. Acceptability of
      Norplant is on the increase, thus, it should be easily available, accessible and
      affordable.

PMID- 14677297
TI  - Parents' attitudes to adolescent sexual behaviour in Lesotho.
AB  - This study investigated the knowledge, attitudes and opinions of parents on
      various aspects of adolescents' sexual and reproductive health in Lesotho. The
      study used a qualitative methodology. Findings reveal that parents are aware that
      male and female adolescents engage in sexual relationships. Some parents believe
      that adolescents are too young to initiate sexual activities while others said
      they don't mind older unmarried adolescents having sex. In addition, parents felt
      that adolescents do not face discrimination in obtaining family planning
      services. In relation to passing sexual and reproductive health knowledge to
      adolescents, there seems to be a dilemma on who should take the responsibility. A
      number of policy implications have emerged from this study. There should be
      awareness campaign for parents who are not aware that adolescents engage in
      sexual relationships. Parents should be encouraged to communicate with their
      adolescent children on sex-related matters. Government should carry on with the
      dialogue on introducing sex education in schools curriculum.

PMID- 14677298
TI  - Unsafe abortions in a developing country: has liberalisation of laws on abortions
      made a difference?
AB  - Unsafe abortion is still a major cause of maternal morbidity and mortality in
      Africa. To assess whether the introduction of legal abortions in South Africa has
      decreased admissions resulting from mid-trimester abortions, a prospective study
      of abortion cases admitted to the King Edward VIII Hospital, Durban, South
      Africa, over a four-month period was carried out. Two hundred and four women were
      admitted with incomplete abortion; 49% of which were spontaneous, 17% certainly
      induced, 10% probably induced, 18% possibly induced and 4.3% legally induced. A
      change in the laws on termination of pregnancy (TOP) has resulted in a decrease
      in cases of incomplete abortion being admitted to the gynaecological wards.
      However, illegal TOPs are still prevalent for a variety of reasons. There is need
      to place more emphasis on the delivery of efficient contraceptive services and
      reproductive health education for women.

PMID- 14677299
TI  - Reproductive health knowledge, attitude and practice among high school students
      in Bahir Dar, Ethiopia.
AB  - This study was carried out to investigate the reproductive health knowledge,
      attitude and practice of high school students in Bahir Dar, Ethiopia. Data were
      collected using self-administered questionnaire and focus group discussions. The
      study revealed that the students had high level knowledge of contraceptives and
      where to obtain contraceptive services; however, level of use was low. Some of
      the reasons given for not using contraceptives include lack of access to
      services, carelessness, unplanned sexual intercourse and pressure from sexual
      partner. The study indicates that young people engage in sexual relationships at
      an early age without protection or with unsafe non-conventional methods. There
      was no significant difference between the demographic variables and contraceptive
      use at first intercourse. Educational level of the respondents was the only
      demographic variable that had significant association with sexual experience (p <
      0.05). We recommend improved access to family planning information and services
      and family life education programmes based on the needs and experience of these
      young people as a potential solution to alleviate their reproductive health
      problems.

PMID- 14677300
TI  - Profiles of infertility in southern Nigeria: women's voices from Amakiri.
AB  - This paper advances understanding of the consequences of female infertility in
      sub-Saharan Africa on the individual level. It illustrates how local meanings of
      infertility are shaped by the social and cultural context and how they influence
      the life experiences and coping behaviours of infertile women in an Ijo community
      in the Niger Delta. Infertility in Amakiri is a stigma. Barren women cannot
      attain full womanhood and join appropriate age associations since they cannot be
      circumcised without having given birth. Uncircumcised women cannot be burried
      within the town, rather, their corpses are buried in a designated forest. The
      paper is based on over twenty years of ethnographic field work, a complete census
      of one of the town's quarters to estimate the level of infertility and on the
      life histories of infertile women. The life histories are used to illustrate how
      women of various ages, educational levels and occupations cope with their common
      experience of infertility.

PMID- 14677301
TI  - Improving quality of care and use of contraceptives in Senegal.
AB  - In the 1990s, the government of Senegal implemented a series of policy changes
      for the provision of family planning services through the public sector. A
      strategy to provide high quality services through reference centres was adopted.
      This paper presents findings from a longitudinal survey of 1,320 Senegalese women
      who had sought family planning services at ten public sector facilities--five
      reference centres and five health centres. Information was collected on the
      quality of care they received at the time they adopted family planning. One
      thousand one hundred and ten of the respondents were followed up sixteen months
      later to ascertain their contraceptive status. The first principal finding was
      that attendees at reference centres reported receiving relative better care than
      those who attended health centres. On average, clients at reference centres
      received 4.3 out of five units of care, compared to 3.8 units as reported by
      health centre clients. Second, multivariate analyses indicated that quality of
      care received at the time of adopting a contraceptive has a significant influence
      on subsequent contraceptive use. Those who received good care were 1.3 times more
      likely to be using a method than others.

PMID- 14677302
TI  - [The woman's status and condom use in Cameroon].
AB  - The reasons for the high prevalence of STDs/HIV/AIDS among women are biological,
      economical and social. It is therefore necessary to carry out studies on the
      status of women and condom use in order to elucidate the mechanism through which
      the first variable affects the second. Such studies will also identify the
      elements to be taken into consideration in the prevention programmes of these
      diseases in women. In the year 2000, a survey on culture, gender, social
      behaviour and STDs/AIDS was conducted in Cameroun at Mbalmayo (Central Province)
      and at Bafoussam (Western Provience) among 1679 men and women of 15-49 years old.
      Multivariate logistic regression models were used, among others, to show that the
      woman's status has direct and indirect effects on condom use via age disparity
      between partners, frequency of discussion among couples on sexuality and the
      process of decision-making. Results obtained confirm this hypothesis.
      Communication among couples as well as women empowerment should, therefore, be
      improved as a strategy for considerably increasing the use of condom among
      Camerounian women. One of the ways to achieve this is to improve their status.
      Another way is to assist them during enlightenment campaigns to improve their
      self-perfection.

PMID- 14677303
TI  - Gender issues in the prevention and control of STIs and HIV/AIDS: lessons from
      Awka and Agulu, Anambra State, Nigeria.
AB  - The study examined perceptions, practices and norms underlying sexuality and
      gender relations that constrain the prevention and control of STIs and HIV/AIDS.
      It was carried out among the Igbo of Awka and Agulu in Anambra State of Nigeria.
      Both quantitative and qualitative methods were used for data collection. Findings
      indicate that cultural practices that encourage the establishment of sexual
      networks by men persist in the study communities. Some married women who are not
      able to achieve pregnancy with their husbands get involved in such networks to
      have children. Some parents who do not have male children encourage their
      unmarried daughters to have children out of wedlock so as to perpetuate the
      lineage. Inequality in gender relations and fear of repercussions constrain women
      from negotiating safe sex. Sexuality education is, therefore, necessary to
      improve the knowledge base, perceptions and sexual behaviours of the study
      communities. Women should be empowered to make informed decisions about sexuality
      and childbearing. Male responsibility in reproductive health should also be
      encouraged.

PMID- 14677304
TI  - Antibiogram and plasmid profiles of Neisseria gonorrhoeae isolates from Cameroon:
      useful tools for epidemiological survey.
AB  - A prospective laboratory-based investigative study was carried out on clinical
      isolates of N. gonorrhoea to determine their antibiotic susceptibility patterns
      and plasmid profile using standard microbiological and molecular techniques. All
      the 32 isolates studied showed total resistance to penicillin, spectinomycin and
      amoxyclinE. On the other hand, susceptibilities of 100%, 98.6% and 98.6% were
      noted for ciprofloxacin, ofloxacin and norfloxacin respectively. Thirty (93.8%)
      of the 32 isolates were found to harbour plasmids of molecular weights ranging
      from 9.2 to 25.2 Mdal. Three distinct groups of N. gonorrhoea isolates were
      identified based on the molecular weights of the plasmids, namely, group one (9.2
      Mdal), group two (12.6 Mdal) and group three (25.2 Mdal). These results suggest
      that different strains of N. gonorrhoea may be circulating in Fako Division of
      Cameroon, a finding that is of clinical and epidemiological significance.

PMID- 14677305
TI  - Bilateral total loss of vision following eclampsia--a case report.
AB  - Visual loss following eclampsia is usually reported to be a result of
      retinopathy, exudative retinal detachment or cortical blindness. This paper
      reports the case of a 31-year-old para 5 + 0 housewife who developed bilateral
      visual loss following eclampsia and presented to the ophthalmologist four weeks
      later with a vision of light perception in both eyes. Examination showed evidence
      of hypertensive retinopathy. Convinced that the ocular findings were not
      responsible for such marked visual loss, she was commenced on systemic, topical
      and sub-conjunctival injection of steroids, acetazolamide and multivitamins. Her
      vision improved progressively to 6/6 right eye and 6/9 left eye after three
      weeks. Obstetricians are advised to refer cases of visual loss following
      eclampsia promptly to the ophthalmologist who should in turn manage aggressively
      with systemic, topical and sub-conjunctival steroids.

PMID- 14677306
TI  - Routine screening for HIV infection in pregnant women: a highly justified
      component of antenatal care in developing countries.

PMID- 14677307
TI  - Paroxysmal positional vertigo: short- and long-term clinical and methodological
      analyses of 794 patients.
AB  - Between 1995 and 2001, eight Italian clinical centres used the same diagnostic
      and therapeutic protocol in order to assess the clinical progress of paroxysmal
      positional vertigo and the benefits of an appropriate follow-up in prevention of
      relapse. The study population comprises 794 patients affected by paroxysmal
      positional vertigo. The study protocol comprised diagnostic staging including a
      complete otoneurological test, an anamnestic questionnaire aimed at identifying
      any possible risk factor, a blood test in basal conditions and monitoring of
      blood pressure. If necessary, more specific instrumental tests have been carried
      out. Appropriate rehabilitative manoeuvres were performed from 1 to 3 times
      within the same session. The patient was checked 3-5 days later: in the presence
      of a positive result, the treatment was repeated; if negative, patients were seen
      at clinical follow-up 7, 30, 180 and 365 days after recovery. Wherever possible,
      patients have been contacted 2 years after the first treatment and asked to
      answer a questionnaire and to attend for a clinical check-up. The incidence of
      paroxysmal positional vertigo appeared to be higher in females and in patients
      aged 50-70 years, being low in patients under 30. In 88.8% of cases posterior
      semicircular canals showed a significant involvement; in 6.8% of cases, only
      involvement of lateral semicircular canals; monolateral (2.7%) and bilateral
      (1.7%) multicanalar forms were rare. Paroxysmal positional vertigo forms
      involving posterior semicircular canals have been treated with Semont (simplified
      by Toupet), Epley, Parnes Price-Jones manoeuvres; those, involving lateral
      semicircular canals with Vannucchi-Vicini forced position and "barbecue" or
      Gufoni manoeuvre. Whilst all these manoeuvres were equally effective, longer
      recovery times have been observed in paroxysmal positional vertigo forms
      involving lateral semicircular canals when the Vannucchi-Vicini forced position
      was ineffective. Any relapses have been evaluated at least 15 days after a
      negative clinical pattern. Possible involvement of other semicircular canals
      (recurrence) some time after the first onset has been considered separately.
      Follow-up at 6 months showed recurrence in 12.4% of cases, while being chronic in
      1.5% of cases. Only 9.3% of cases showed recurrence at 6 months, no statistically
      significant difference being observed between vertical (8.9%) and lateral canal
      (9.6%), forms. Relapses occurred in 3.1% of cases, in one third of which at least
      two risk factors were detected.

PMID- 14677308
TI  - Treatment of benign paroxysmal positional vertigo of posterior semicircular canal
      by "Quick Liberatory Rotation Manoeuvre".
AB  - Treatment of Benign Paroxysmal Positional Vertigo is based on Semont's Liberatory
      Manoeuvre and on so-called "Canalith Repositioning Manoeuvres", derived from the
      original Epley technique. Both manoeuvres are very effective and choice of which
      to use depends on the experience of the physician. Semont's manoeuvre requires a
      quick movement of the patient in mass in the frontal plane, from the involved, to
      the contralateral side, which sometimes causes symptoms such as nausea or
      vomiting. In this technique, a secondary liberatory nystagmus is often observed
      as sign of the success of the manoeuvre. Repositioning manoeuvres are less
      fastidious because of the slow movements, but we rarely observe an objective sign
      of success like the liberatory nystagmus. In the present randomised trial, 300
      patients with posterior canalo/cupulolithias were divided into 3 treatment
      groups: 100 treated by Semont Technique; 100 by a Repositioning procedure (Parnes
      technique); 100 by a new manoeuvre called "Quick Liberatory Rotation". Results of
      treatment are also compared with the natural evolution of Benign Paroxysmal
      Positional Vertigo observed in 18 untreated patients. Quick Liberatory Rotation
      is similar in the sequence of the positions of the head in the horizontal plane,
      to repositioning procedures, but is more like the Semont manoeuvre in the speed
      of the movement (about 180 degrees in less than one second). Quick Liberatory
      Rotation is easy to perform, well tolerated and very effective (success rate: 98%
      in one-three cycles). In the present investigation, a secondary liberatory
      nystagmus was observed in 76.1%, with a sensitivity of 81.9% in detecting
      patients who had completely recovered and a specificity of 43.8% in detecting
      failures. Effectiveness, in short and medium period (1-15 months), is similar to
      Semont and Parnes techniques. Authors consider Quick Liberatory Rotation, at
      present, a possible first choice technique in the treatment of posterior
      canalolithiasis.

PMID- 14677309
TI  - Allergic fungal sinusitis. A naso-sinusal specific hyperreactivity for an
      infectious disease?
AB  - Allergic fungal sinusitis (AFS) is a rare disease of naso-sinusal complex
      affecting mainly young, immunocompetent adults who complain of chronic rhinitis
      and/or recurrent nasal polyposis despite medical and/or surgical treatment. Aim
      of the study is to analyse, from an allergological and otorhinolaryngological
      point of view, patients affected by the so-called "allergic fungal sinusitis" in
      order to better define the relationship between fungi present in naso-sinusal
      secretions and the host's immunoreactivity. From February 2001 to January 2002,
      24 selected patients (13 male 11 female) age range 25-65 years (mean 45), with
      chronic rhinosinusitis, with a positive fungal examination of nasal secretion,
      underwent allergological evaluation. All patients were positive for diagnostic
      criteria of allergic fungal sinusitis and, in all patients, nasal lavage was
      performed for microscopic examination by fluorescence. Samples were then cultured
      on Sabouraud growth media for identification of the fungus. Skin prick tests
      (SPT) were then performed with the 15 main inhalant allergens and twelve fungal
      allergens (Bracco). The total IgE serum level (PRIST), the specific fungal IgE
      and the eosinophilic cationic protein were then investigated by means of an
      immuno-fluorine enzymatic method. Finally, a nasal provocation test was carried
      out with diluted solutions (1/100, 1/10) and with a pure solution of fungal
      allergens, selected according to microbiological examination of nasal secretion
      of each subject. Prick tests were positive for seasonal and perennial allergens
      in 5 patients (21%), while prick tests with fungi were positive in only 4
      patients (16.6%). Total IgE levels were higher than in normals (200 KU/l) in 6
      patients (25%) (mean 364.74 KU/l). In another 18 patients, total IgE were normal.
      Specific IgE levels for the tested fungi and eosinophilic cationic protein levels
      were within normal range in all patients. Nasal provocation test was negative in
      all patients. Presence of fungi in nasal secretions of patients with AFS does not
      appear to be correlated with an allergic status to the isolated fungus. A role
      for IgE in either the aetiology or the pathophysiology of allergic fungal
      sinusitis in unlikely, and probably the diagnostic criteria for allergic fungal
      sinusitis should not include type I hypersensitivity, since no confirmed evidence
      exists that IgE-mediated type I hypersensitivity is involved in the
      pathophysiology of allergic fungal sinusitis.

PMID- 14677310
TI  - Role of endoscopic CO2 laser surgery in the treatment of congenital infantile
      subglottic hemangioma. Experience in the Department of Otolaryngology, "Sick
      Children Hospital", Toronto, Canada.
AB  - Subglottic hemangioma is a rare, histologically benign congenital neoplasm. The
      natural history is characterized by progressive obstruction of the airways during
      the proliferative stage, followed by gradual regression of the obstructive
      symptomatology in the involutional phase. After an asymptomatic neonatal period,
      the infant presents a characteristic biphasic stridor as the lesion progressively
      obstructs the subglottic space. In 80-90% of cases, these symptoms appear in the
      first six months of life. The involutional process generally begins at 12 months
      of age and continues until the subglottic hemangioma regresses completely. Due to
      high incidence of mortality in untreated cases, therapy should be undertaken
      immediately. Aim of therapy is to restore normal respiration, attempting to
      preserve the child's voice and alter the quality of life both of the infant and
      the family as little as possible. A retrospective study was carried out on all
      cases of infantile subglottic hemangioma treated in the Department of
      Otolaryngology, "Sick Children Hospital", Toronto, between 1980 and 2000. The
      therapeutic strategy adopted until breathing returned to normal comprised
      repeated endoscopic CO2 laser treatment of the lesion and perioperative
      administration of oral cortisone (1 mg/kg/day dexamethazone, subdivided in 3
      doses) for 24-48 hours. CO2 laser was used each time the patient presented
      progressive worsening of obstructive respiratory symptoms. The interval between
      two laser treatments was > or = 6 weeks. Repeated endoscopic laser treatment,
      combined with other therapeutic modalities, enabled tracheotomy to be avoided in
      all but 4 (7.2%) cases.

PMID- 14677311
TI  - Swallowing disorders: management data.
AB  - Aim of the investigation was to assess the workload and verify the results of
      oropharyngeal dysphagia management in a large state hospital by means of a
      descriptive, observational prospective study and descriptive statistical
      analysis. 81 patients [37 females, 44 males, mean age 61.3 (+/- 13) years]
      suffering from oropharyngeal dysphagia were evaluated and treated in the in- and
      outpatient Divisions of the "Azienda Ospedaliera S. Giovanni Battista" in Turin.
      Treatment of oropharyngeal dysphagia included changes in consistency and texture
      of food, compensatory postures of head, strengthening exercises for oropharyngeal
      muscles, and stimulation of pharyngeal sensitivity. In data collection and
      analysis, the following were used as outcome measures: mode of nutrition delivery
      (oral, enteral, parenteral), dietary adjustments, presence of aspiration or
      penetration, and use of compensatory head positioning. Results showed that the
      number of patients fed by parenteral or enteral tube (50/81 prior to treatment)
      dropped to 36/81 upon discharge from hospital. Those unable to take anything by
      mouth, from 55 dropped to 9. The number of patients with aspiration or
      penetration dropped, respectively, from 47 and 8 to 20 and 4. Postural changes
      were used in 15 cases. Data obtained indicate that oropharyngeal dysphagia
      rehabilitation outcomes are promising. Better understanding of the rheological
      characteristics of food and a stricter, more rigorous evaluation of the outcomes
      on activities and social participation are warranted.

PMID- 14677312
TI  - Voluminous frontoethmoidal mucocele with epidural involvement. Surgical treatment
      by coronal approach.
AB  - The case is described of mucocele of the right frontoethmoidal sinus with
      bilateral maxillary sinusitis and a large polyp in the right nasal cavity. The
      mucocele had determined erosion of the anterior and posterior walls of the
      frontal sinus and superomedial wall of the orbit. The patient was operated upon
      by a surgical team comprising ENT and maxillofacial specialists. Right maxillary
      sinusotomy (Caldwell-Luc procedure) was performed, and an osteoplastic flap was
      prepared, repositioned in the canine fossa and fixed with a titanium plate.
      Debris was removed from the left osteomeatal complex during endoscopy. To reach
      the mucocele, an external surgical approach was used, through a bitemporal
      coronal cutaneous incision, according to Unterberger. This approach was used in
      order to gain better access to the area of the lesion and in order to make
      reconstruction easier, with a view to achieving good functional results without
      untoward scarring. The scalp was detached down to the root of the nose to allow
      optimal visualisation of the anterior area of erosion determined by the mucocele,
      and, after excision and removal of the latter from the bony walls, of the
      posterior bony breach and underlying dura mater. Another bony breach involved the
      medial and superior walls of the orbit. The nasofrontal canal was obliterated
      with bone fragments and Tissucol; the posterior breach, with Surgical and
      Tissucol. The orbit wall was repaired with high-density porous polyethylene
      sheeting; the frontal sinus was filled with fat. The anterior wall of the frontal
      sinus was repaired with two split of calvarial bone grafts harvested from the
      parietal bone and fixed with a titanium microplate. The morphological outcome of
      reconstruction was satisfactory, with no recurrences, as confirmed at post
      operative follow-up, including computed tomography scan, at 5 months. Ocular
      motility and patency of the tear drainage system were also normal. No diplopia,
      or inflammation occurred.

PMID- 14677313
TI  - Angiosarcoma of the larynx. Case report and review of the literature.
AB  - Angiosarcoma of the larynx is a rare malignant tumour of vascular origin,
      accounting for less than 1% of all malignant tumours of the larynx. Angiosarcoma
      involves, in particular, the head and neck in areas such as the scalp and face.
      The causes are unknown, even if, in some cases, it is believed to be radiation
      induced. The case is described of a patient with hypopharyngolaryngeal
      angiosarcoma, which became manifest with dysphagia, dysphonia and a palpable
      right latero-cervical mass about 7 cm in length. The patient underwent total
      pharyngolaryngectomy, right hemithyroidectomy, and bilateral neck dissection.
      Histological examination of the surgical specimen revealed a large haemorrhagic
      lesion involving the right pyriform sinus and homolateral hemilarynx. Right
      radical neck dissection revealed 9 metastatic lymph nodes, 1 of which with
      capsular invasion. Upon complete recovery the patient, underwent adjuvant post
      operative radiotherapy. Six months later she is still alive with no clinical or
      radiological signs of disease. A careful review of the literature produced very
      few reports of such cases, only 6 of which in the last 30 years. Survival rate is
      very low, even if feasible average can be advanced, in view of the paucity of the
      case reports. Histological diagnosis is not always straightforward, as this
      neoplasm may be misdiagnosed as other vascular tumours (Kaposi's sarcoma,
      haemangiopericytoma), as non-neoplastic lesions (granulomas secondary to
      intubation) and as poorly differentiated squamous cell carcinoma.
      Immunohistochemical evaluation by means of markers, such as vimentin and factor
      VIII, offers a significant contribution to the diagnosis of angiosarcoma. The
      treatment of choice for laryngeal angiosarcoma is surgical excision, ample and
      radical, whenever possible, followed by adjuvant post-operative radiotherapy.

PMID- 14677314
TI  - Tracheocoele in a Duchenne muscular dystrophy patient. Case report.
AB  - Tracheocoele, a congenital or acquired lesion, is rarely detected radiologically
      and even more rarely diagnosed clinically. This tracheal lesion is characterised
      by the presence of a single cystic lesion filled with air or a mixture of liquid
      and air, of extremely variable size, occurring in almost all cases, in a locus
      minoris resistentiae situated in the right posterolateral portion of the trachea.
      The rare case is described of a voluminous tracheocoele located in the left
      paratracheal region, extending from the cricoid to sternal notch, manifesting
      clinically, 3 months prior to evaluation in our hospital in a 27-year-old male
      suffering from Duchenne muscular dystrophy since the age of 5 years. For 10
      years, the patient had been treated with intermittent positive pressure
      ventilation via nasal mask, due to progressive deterioration of respiratory
      function. Diagnosis of tracheocoele, initially made at computed axial tomography
      scan, was confirmed by flexible laryngotracheoscopy under local anaesthesia. Due
      to severe comorbidity associated with the clinical picture described, the absence
      of a significant set of symptoms, and the problems concerning anaesthesiological
      management of the patient, palliative treatment was the only choice. This
      consisted in cervical compression bandaging during assisted nasal ventilation.
      Close follow-up was performed in order to monitor any progression of the lesion
      or onset of related complications. This is the second case of tracheocoele
      originating in the left paratracheal region reported in the literature, and the
      first associated with Duchenne muscular dystrophy and prolonged use of a positive
      pressure respirator. The aetiopathogenic mechanisms that may have determined the
      formation of this rare lesion are then taken into consideration.

PMID- 14677315
TI  - Concomitant primary hyperparathyroidism, Graves' disease and vitamin D
      deficiency.
AB  - The simultaneous occurrence of hyperthyroidism and primary hyperparathyroidism is
      quite rare. A case is reported here of Graves' disease and primary
      hyperparathyroidism. Treatment of these concomitant diseases consists in combined
      thyroidectomy and parathyroidectomy. Histological examination confirmed Graves'
      disease and revealed the presence of a parathyroid adenoma in one gland and
      parathyroid hyperplasia in another one. After surgical treatment, secondary
      hyperparathyroidism due to 25-OH Vitamin D deficiency appeared. To our knowledge,
      this is the first case in which a Vitamin D absorption deficit was found in
      presence of hyperthyroidism and hyperparathyroidism without other intestinal
      absorption deficits. Diagnostic and follow-up difficulties related to these three
      concomitant pathological conditions are discussed.

PMID- 14677316
TI  - [Relationship between health economics and bioethics in otorhinolaryngology.
      Round table discussion at 26th National Congress of Italian Otorhinolaryngology,
      Udine, September 20-21, 2002].

PMID- 14677317
TI  - [Research on evaluation of bibliometric indices for Italian scientific production
      in otorhinolaryngology].

PMID- 14677318
TI  - Nursing interventions for a chronically ill, nonadherent teenager with a
      psychiatric diagnosis.
AB  - ISSUES AND PURPOSE: To describe the complex care of an adolescent with chronic
      psychiatric and medical problems. CONCLUSIONS: The nonadherent, self-abusing,
      adolescent was empowered to progress developmentally, as well as medically.
      PRACTICE IMPLICATIONS: A planned team approach helped the adolescent become more
      developmentally appropriate and independent in self-care. The care plan designed
      by nursing staff included a change in nursing focus, creative problem solving,
      team nursing, and utilization of multidisciplinary resources.

PMID- 14677319
TI  - Mothering in public: a meta-synthesis of homeless women with children living in
      shelters.
AB  - ISSUES AND PURPOSE: The purpose of this paper is to synthesize the current
      qualitative literature on homeless women with children living in shelters.
      METHODS: Eighteen qualitative studies on homeless women with children living in
      shelters were included in the synthesis. The meta-synthesis was conducted using
      the meta-ethnographic approach of Noblit and Hare (1988). RESULTS: Six reciprocal
      translations (themes) of homeless mothers caring for their children in shelters
      emerged: On becoming homeless, protective mothering, loss, stressed and
      depressed, survival strategies, and strategies for resolution. PRACTICE
      IMPLICATIONS: The results may be used by healthcare workers as a framework for
      developing intervention strategies directed toward helping mothers find new
      solutions to dealing with shelter living and innovative ways to resolve their
      homelessness.

PMID- 14677320
TI  - The development of trust in parents of hospitalized children.
AB  - ISSUES AND PURPOSE: The purpose of this study was to investigate the development
      of trust in parents of hospitalized children. METHODS: Using grounded theory,
      semistructured interviews were conducted with 15 parents of children previously
      hospitalized, focusing on parents' experiences during their child's
      hospitalization. Data were analyzed using a constant comparative process. Themes
      and the core variable were identified and a model of trust developed. RESULTS:
      The core variable related to the development of trust in healthcare providers was
      whether parents' expectations for care were met. Thematic areas that influenced
      whether expectations for care were met included preexisting trust; evaluation of
      care, including evaluation of technical skills and the meeting of parental and
      child needs; and behaviors of nurses and other healthcare providers that
      inhibited and fostered trust. PRACTICE IMPLICATIONS: Strategies to enhance trust
      are discussed.

PMID- 14677321
TI  - Rapid-cycle improvement in pediatric health care: a solution for patients with
      similar or same last names.

PMID- 14677322
TI  - Care teams of respiratory therapists and nurses in a PICU setting.

PMID- 14677323
TI  - Public health approaches in diabetes prevention and control.

PMID- 14677324
TI  - Translating the science of primary, secondary, and tertiary prevention to inform
      the public health response to diabetes.
AB  - Diabetes is emerging as a major focus of public health efforts in the United
      States and worldwide because the burden of the disease is increasing rapidly. The
      increasing prevalence of diabetes is alarming because of the broad spectrum of
      acute and long-term complications that typically occur in combination and lead to
      extensive disability and substantial mortality, while imposing substantial human
      and economic costs on individuals, families, communities, health care systems,
      and society. Diabetes management was once considered the domain of the physician
      patient relationship, guided by basic science and clinical research. Research
      focused on the physician-patient relationship is now being complemented with risk
      reduction media campaigns, health services research, and community-based
      participatory research. This article summarizes key scientific studies of
      primary, secondary, and tertiary prevention that provide evidence that diabetes
      complications can be prevented and controlled. We also discuss how findings from
      large-scale randomized clinical trails support the critical need for
      complementary public health approaches to address and eliminate persistent health
      disparities, using health systems, health communications, and community
      intervention research and practice.

PMID- 14677325
TI  - Mobilizing communities: local applications of the Diabetes Today national
      training center project.
AB  - In 1992, the Division of Diabetes Translation developed the Diabetes Today
      program to train representatives of state and local health departments on how to
      develop, implement, and evaluate community-based diabetes prevention and control
      programs. This commentary briefly describes the evolution of the Diabetes Today
      program in the United States. The Diabetes Today program utilizes a training
      curriculum to increase expertise in community assessment; coalition building;
      adult-learn principle, program planning, implementation, and evaluation. The
      training curriculum contains four modules: defining diabetes and mobilizing a
      community response; assessing diabetes in your community; planning your diabetes
      program, and evaluating your diabetes program. Two versions of the curriculum
      have been utilized--one in English and the other in Spanish. This commentary
      presents two examples of Diabetes Today efforts--The Missouri Diabetes Control
      and Prevention (English) and the United States/Mexico Border Diabetes Project
      (Spanish version)--to briefly describe how this program planning, implementation,
      and evaluation model can generate a community response to diabetes.

PMID- 14677326
TI  - Empowerment through community building: Diabetes Today in the Pacific.
AB  - The goal of Diabetes Today, a program of the Centers for Disease Control and
      Prevention (CDC), is to develop coalitions and train coalition members in
      assessment, planning, and evaluation to address diabetes in their communities.
      CDC established the Pacific Diabetes Today Resource Center (PDTRC) in 1998 to
      tailor the program for Pacific Islander communities in Hawaii, American Samoa,
      Guam, the Commonwealth of the Northern Marianas Islands, the Federated States of
      Micronesia, the Republic of the Marshall Islands, and Palau. PDTRC's work is
      guided by the principles of community building and the goal of empowering
      coalitions to take action around diabetes. Culturally appropriate strategies are
      used to gain access to the community, transfer knowledge and skills, build
      coalitions, and provide technical assistance. Evidence of empowerment is seen in
      increased individual competence, enhanced community capacity, reduced barriers,
      and improved supports to address diabetes. To maintain the gains of community
      building in the Pacific, three factors appear critical: an engaged leader, a host
      agency for the coalition, and continuing access to technical assistance and
      funds.

PMID- 14677327
TI  - Sharing a vision of hope for diabetes care and prevention among American Indian
      and Alaska Native communities: the National Diabetes Prevention Center.
AB  - The National Diabetes Prevention Center (NDPC) is an emerging model for public
      health practice and partnership. It is rooted in a "promising practices"
      framework, one that looks at what works for community diabetes prevention, care,
      and treatment practices. Working with national and local partners to explore new
      approaches to diabetes prevention invites us to move beyond traditional models of
      community public health partnerships. Traditional community partnership models
      emphasized the technical assistance in research, surveillance, and program
      development that can be provided by partners from outside the community. While
      not diminishing the importance of these activities, the NDPC seeks to provide an
      environment for meaningful language and discourse that adequately honors the
      innovative and culturally rich approaches to diabetes prevention already being
      developed within many American Indian and Alaska Native communities, which have
      some of the highest rates of diabetes in the world. The NDPC strives to provide
      common ground for the emergent discussions around the power and practice of solid
      evaluation frameworks, new information technologies, capacity-building
      philosophies, health systems, and collaborative approaches.

PMID- 14677328
TI  - Examining diabetes health benefits in health plans of large employers.
AB  - Components of the contract specifications (also known as model purchasing
      specifications) for diabetes care that were developed by George Washington
      University (Washington, D.C.) and the Centers for Disease Control and Prevention
      were applied to 20 health plans from two Fortune 500 companies as well as the
      Federal Employee Health Benefits Plan to investigate the extent of diabetes
      related benefits available to employees. Diabetes-related benefits covered a
      range of services and supplies that include insulin, physician visits,
      immunizations, diabetes preventive assessments, foot and eye exams, hemoglobin
      A1c tests, orthotics, diabetes self-management education, case management,
      smoking cessation, obesity treatment, and exercise training. The 20 health plans
      included health maintenance organizations, preferred provider organizations,
      point of service plans, and one indemnity plan. Services and supplies were
      assigned to three tiers: tier 1, general diabetes care; tier 2, specialty
      diabetes care; tier 3, lifestyle services. Services and supplies were considered
      covered even if they required authorization by the provider (e.g., doctor
      referral, recommendation, or prescription) or the health plan. Tier 1 services
      and supplies received more comprehensive coverage by all health plans.
      Differences in coverage were more notable in tiers 2 and 3 than in tier 1. Tier 3
      (lifestyle services) received less coverage than tiers 1 and 2.

PMID- 14677329
TI  - Improving diabetes care and outcomes: the secondary benefits of a public health
      managed care research collaboration.
AB  - The project improving Diabetes Care through Empowerment, Active Collaboration and
      Leadership (IDEAL) is a collaborative translational research project of the
      Minnesota Diabetes Program (MDP) at the Minnesota Department of Health and
      HealthPartners (HP), a large managed care organization. The research was designed
      to test a quality improvement model to improve diabetes care delivery and
      outcomes in primary care clinics, but the collaboration was structured from the
      beginning to maximize potential secondary effects. The MDP and HP participated
      jointly in every aspect of the project. Personnel from other health care systems
      and academic and quality improvement organizations also participated in IDEAL.
      Secondary effects included heightened priority for diabetes care improvement at
      HP and within its medical group, along with an increased emphasis on a population
      approach for both of these organizations. Simultaneously, the MDP developed a
      better understanding of the issues and potential for improving care in primary
      care clinics, medical groups, and managed care organizations. These benefits
      resulted in further collaboration between the MDP, HP, and other managed care,
      health care, and quality improvement organizations in Minnesota. Thus, Project
      IDEAL has been a successful collaboration of public health and managed care whose
      contribution to improved diabetes care in Minnesota health systems extends far
      beyond the original scope of the project.

PMID- 14677330
TI  - Public health surveillance of diabetes in the United States.
AB  - The Centers for Disease Control and Prevention Division of Diabetes Translation
      supports a national and state surveillance system that analyzes, interprets, and
      reports on diabetes risk behaviors, risk factors, care practices, morbidity, and
      mortality. Data sources include surveys, the U.S. Renal Data System, the Indian
      Health Service, information on hospital inpatients, birth and death certificates,
      and special studies to use and to better understand the usefulness of data from
      managed care, Medicare, and Medicaid for monitoring diabetes. These data are used
      to define the magnitude and burden of diabetes; monitor changes in burden over
      time; guide public health planning and policy making, and assess progress toward
      diabetes objectives, such as those in Healthy People 2010. Challenges facing the
      diabetes surveillance system are limitations in data sources; the capture of
      undiagnosed diabetes; tracking key risk factors, such as levels of glycemia and
      lipids; and surveillance of high- or emerging-risk populations such as racial and
      ethnic groups, children and youth, and those with prediabetes. Limited resources,
      competing priorities, and issues of data privacy also challenge surveillance. To
      overcome these factors, the Division of Diabetes Translation strongly emphasizes
      partnering with other organizations, such as the Medicare and Medicaid programs,
      managed care, and other chronic disease programs.

PMID- 14677331
TI  - Use of data from the Behavioral Risk Factor Surveillance System optional diabetes
      module by states.
AB  - An optional diabetes module of the Behavioral Risk Factor Surveillance System was
      first made available to states in 1993. In 2002, 49 states administered this
      module. In October 2001 we asked state Diabetes Prevention and Control Program
      coordinators to complete a two-part questionnaire regarding the use of data from
      the diabetes module and their usefulness in guiding programmatic activities.
      Seventy percent of state coordinators reported using data from at least one
      module question to perform program evaluation, develop publications, and
      development of community interventions; 45 percent of coordinators used data from
      at least one module question for activities related to passage of legislation.
      Questions on self monitoring of blood glucose, hemoglobin A1c test, annual foot
      exam, annual dilated eye exam, and diabetes education were rated as highly useful
      by the state coordinators. The results from the optional diabetes module are
      widely used by states and are essential to Diabetes Prevention and Control
      Program activities. It is important that the optional diabetes module continue to
      be included in each state's yearly Behavioral Risk Factor Surveillance System.

PMID- 14677332
TI  - Learning from listening: common concerns and perceptions about diabetes
      prevention among diverse American populations.
AB  - Recent research findings confirming the feasibility and effectiveness of
      interventions to prevent or delay the onset of type 2 diabetes are of keen
      interest to many stakeholders, including communities from which diabetes exacts a
      heavy toll. To inform communication and program planners at national and local
      levels, the Division of Diabetes Translation, Centers for Disease Control and
      Prevention, turned to people and communities affected by diabetes for their views
      about diabetes prevention. We review the key themes that emerged across diverse
      populations and some examples of subthemes relevant to particular groups. Adults
      at risk for type 2 diabetes and community leaders from five racial and ethnic
      groups participated in 27 focus groups from five geographic locations across the
      country. We explored participants' knowledge, attitudes, and beliefs about
      diabetes and factors that would enable or impede lifestyle interventions at
      individual and community levels. Multiple analysts categorized responses using
      the qualitative technique of constant comparison. Many themes, some cutting
      across groups and some unique to specific groups, emerged about the negative
      effect of modern lifestyles on the health of adults and children. But positive
      findings about diabetes prevention generated hope that diabetes was not
      inevitable. All the focus groups noted that interventions were difficult to
      initiate and maintain and that social support, modeling stories, and community
      connections were needed. Listening to community members identified common and
      group-specific themes. These findings can inform health promotion messages and
      support adaptive community interventions for diabetes prevention.

PMID- 14677333
TI  - The National Diabetes, Influenza, and Pneumococcal Campaign: an evaluation of
      campaign relevancy, partnerships, and media relations.
AB  - The Division of Diabetes Translation, Centers for Disease Control and Prevention,
      collaborated with its 59 Diabetes Prevention and Control Programs (DPCPs) to
      implement in 1998-1999 the National Diabetes Influenza and Pneumococcal Campaign.
      Postcampaign evaluation examined DPCPs' perceptions of the relevancy of the
      campaign in reaching the target population (adults aged 25-64 years with
      diabetes), establishing successful partnerships, and engaging the media. Most
      DPCPs stated the campaign reached their target population. DPCPs most commonly
      partnered with existing networks such as public health organizations or
      government agencies and direct health care providers. A majority of DPCPs did not
      find partnerships with direct health care providers to be effective in this
      campaign, but public health organizations, peer review organizations, and
      coalitions were described as successful partners. States in which DPCPs conducted
      follow-up calls to television stations regarding the airing of public service
      announcements generally had more announcements aired than states in which such
      calls were not made. Postcampaign evaluation findings also indicate that DPCPs
      who attempted to engage nontraditional partners (e.g., media outlets) achieved
      greater campaign success than those who did not. Future campaign efforts will
      likely benefit from relationships established with nontraditional partners, such
      as retailers, media outlets, local pharmacies, and faith-based organizations.

PMID- 14677334
TI  - The role of a historically black university and the black church in community
      based health initiatives: the project DIRECT experience.
AB  - This work explores the role of North Carolina Central University (NCCU), a
      historically Black university, and local Black churches in serving as community
      resources in Project Diabetes Interventions Reaching and Educating Communities
      Together (Project DIRECT). Project DIRECT is a federally funded participatory
      research project sponsored by the Centers for Disease Control and Prevention. The
      rationale for involving NCCU is presented. The authors review how faith-centered
      strategies were used in local churches to create social and environmental changes
      to support diabetes prevention and control. Involving historically Black colleges
      and universities and Black churches in health promotion at the community level
      represents an excellent example of how local institutional resources can help
      eliminate health disparities.

PMID- 14677335
TI  - "Managed care".

PMID- 14677336
TI  - Practice of acupuncture and laser hair removal.

PMID- 14677338
TI  - Together for the future of medicine.

PMID- 14677337
TI  - Doctor, who's in your corner? Michigan State Medical Society is.

PMID- 14677339
TI  - Patterns of anticoagulation in patients hospitalized with atrial fibrillation:
      warfarin is underused in paroxysmal atrial fibrillation.
AB  - Paroxysmal atrial fibrillation (PAF) has a similar stroke risk when compared with
      chronic atrial fibrillation (CAF). Our study sought to define the incidence of
      warfarin use at time of admission and discharge in patients hospitalized with PAF
      and CAF. Anticoagulation rates upon hospital admission were 89% in the patients
      with CAF and 38% in patients with PAF, and increased to 100% for patients with
      CAF and 81% for patients with PAF at the time of hospital discharge. Despite a
      similar risk of stroke, patients with paroxysmal atrial fibrillation were less
      likely to receive long-term oral anticoagulation (AC) compared to patients with
      chronic atrial fibrillation.

PMID- 14677341
TI  - Are there ethnic differences in heart failure medication response?

PMID- 14677340
TI  - Hospital readmissions of elderly patients hospitalized with pneumonia.
AB  - BACKGROUND: Readmission is an important outcome that is common among elderly
      patients surviving hospitalization. In this study we describe readmissions and
      examine potential predictors of readmission among elderly individuals with an
      index admission for pneumonia. DESIGN: Retrospective database analysis. SETTING:
      Tertiary care hospital. PARTICIPANTS: Eight hundred and ninety-two patients (> or
      = 65 years) were discharged with a diagnosis of pneumonia. METHODS: Readmissions
      and potentially relevant data were retrieved from the hospital's administrative
      database. RESULTS: Readmissions were experienced by 410 (46.0%) patients. There
      were 739 readmissions (.83/patient). Male gender, a longer index length of stay,
      and cancer comorbidity provided a weak but significant prediction of readmission.
      CONCLUSIONS: Readmissions were common following index admission for pneumonia.
      Data readily available in a hospital administrative database were not
      particularly predictive of readmission. Other, preferably modifiable variables
      will have to be identified if this important outcome is to be addressed.

PMID- 14677342
TI  - The institutional health-care balancing act (autonomy vs accountability and
      responsibility).

PMID- 14677343
TI  - The Cruzan case revisited.

PMID- 14677344
TI  - Evidence based medicine: what's new--what's not--what's needed.

PMID- 14677345
TI  - The need for structured drug/alcohol education.

PMID- 14677346
TI  - SARS.

PMID- 14677347
TI  - A wake-up call for our health-care system.

PMID- 14677348
TI  - Osteoporosis in older men and women.

PMID- 14677349
TI  - Re: Complementary and alternative medicine.

PMID- 14677350
TI  - [Present and future of pediatric urology].

PMID- 14677351
TI  - [Pediatric urology in Europe in 2001].

PMID- 14677352
TI  - [Transanal endorectal pull-through with short muscular cuff in the treatment of
      Hirschsprung disease. Preliminary study with 37 patients].
AB  - INTRODUCTION: Totally transanal operation for classic Hirschsprung's disease has
      gained increasing popularity during the last few years. The procedure leaves no
      scars, is associated with less postoperative pain and discomfort and shortens
      hospital stay. The most commonly used technique for transanal pull-through is
      long endorectal dissection leaving a long muscular cuff, which is usually split
      posteriorly. We present our preliminary results following transanal endorectal
      operation with a short unsplit muscular cuff. MATERIALS AND METHODS: Thirty-seven
      patients underwent short-cuff transanal endorectal operation for Hirchsprung's
      disease between years 2000 and 2002. Patients' hospital records were analysed
      retrospectively. The collected data included age at the operation, associated
      conditions, hospital stay and time to full enteral feeds, occurrence of pre- and
      postoperative enterocolitis and preoperative stoma, operative complications, need
      for postoperative anal dilatations, postoperative perianal skin problems and
      preliminary data on bowel function. RESULTS: The median age at operation was 5
      months (range 0-60 months), 13 patients were operated in the neonatal period. Six
      patients had Down's syndrome, 1 had cartilage-hair hypoplasia and one Ondine's
      syndrome. Six patients had preoperative enterocolitis. Thirteen patients had
      undergone levelling stoma formation for unremitting obstruction or enterocolitis,
      two of these had a long segment aganglionosis. The proximal ganglionic stoma was
      concomitantly pulled-through and anastomosed to the anus in all 13 patients with
      a stoma. Complications related to surgery occurred in 3 patients, 2 had prolapse
      of the pulled-through bowel (reduced immediately without later sequels) and 1
      infection in the stoma closure wound. Median postoperative hospital stay was 4
      days (range 2-21 days) and median time to full enteral feeds 3 (range 1-14) days.
      The median follow-up time was 6 months (range 1-22 months). Postoperative
      enterocolitis occurred in 1 patient, further 3 patients had symptoms suggesting
      mild enterocolitis. Nine patients required anal dilatations, two of those for a
      period of 3 weeks. Twenty-two patients had perianal skin rash, which resolved
      usually within 6 weeks. Early postoperative bowel function was characterised by
      frequent bowel movements in most patients. These usually resolved within few
      months; of the 17 patients with a follow-up for longer than 6 months only 2 have
      more than 3 bowel movements per day. At last follow-up frank soiling occurred in
      2 patients, one patient needs oral laxatives for constipation. CONCLUSIONS:
      Transanal endorectal pull-through with a short cuff is a safe operation with low
      incidence of operative and postoperative complications. Hospital stay and time to
      full enteral feeds is significantly shorter than following conventional
      procedures; this associates with lower hospital costs. Long-term functional
      outcome of patients having totally transanal pull-through is unclear but short
      tern function is very similar than after procedures where transanal mucosectomy
      is combined with rectosigmoid dissection through laparotomy.

PMID- 14677353
TI  - [Ultrasound-guided hydrostatic reduction for the treatment of idiopathic
      intestinal invagination].
AB  - The more extended conservative treatment in intussusception consists of the
      accomplishment of fluoroscopy guided neumoenema. The development of the
      echography has allowed to introduce this as alternative in diagnosis and
      treatment of intussusception. Our objective is to analyze the therapeutic value
      of echography during resolution of intussusception with saline solution enema in
      pediatric patients. Intestinal intussusception was diagnosed in 183 patients by
      echography during a period of 7 years. Patients are classified in three groups
      according to treatment by means of opaque enema, radioscopy guided neumoenema or
      echography guided hydrostatic reduction enema. The results of the three series
      are analyzed: rate of failure of the procedure, the recurrences or the presence
      of complications. We exclude n = 18 patients that were operated on directly after
      the diagnosis. The reduction rate was 81.25% (9/16) with opaque enema; 94.6%
      (103/110) with neumoenema and 96.4% (27/28) with echography guided saline enema.
      Complications appeared in n = 2 cases of intestinal perforation, 1 with barium
      and 1 with air 2. Recurrences were n = 3, n = 2 with neumoenema and n = 1 with
      echography guided enema. Echography guide saline enema has a high security and
      effectiveness (96.4%), similar to the other methods, avoiding the exposition to
      ionic radiation. The technique is safe and it does not increase the rate of
      recurrences.

PMID- 14677354
TI  - [Severe complications in the treatment of vascular anomalies].
AB  - BACKGROUND: Success in the treatment of vascular anomalies during infancy depends
      on an accurate early diagnosis and a correct therapeutic management. Current
      available resources can be divided into pharmacologic, endovascular, surgical,
      and laser. Results are variable, and complications should always be kept in mind.
      METHODS: We reviewed all patients with vascular anomalies who suffered from major
      complications directly due to the treatment during the past five years. RESULTS:
      1. A patient with an upper lip hemangioma following treatment with interferon
      after no response to steroids. A long-term severe neutropoenia forced to an early
      surgical excision of the lesion. 2. A patient suffering from an orbitary
      hemangioma with severe exoftalmus was treated with interferon because of a
      steroid-resistance. A spastic diplegia due to interferon reverted after treatment
      was discontinued. 3. In a patient with a Blue-Rubber Bleb Nevus syndrome,
      extended percutaneous sclerosis was performed. She developed skin necrosis of the
      left leg and a permanent sciatic nerve paralysis. 4. In a patient with an
      arteriovenous malformation on the right leg and gluteous, a femoral artery
      endoprosthesis was placed because of a massive bleeding. She underwent a total
      excision of the malformation and developed a recurrent ischemia related to a
      femoral thrombosis. Finally a foot amputation was needed. 5. A patient with a
      Kaposi-like hemangio-endothelioma who was following a high-dose prolonged steroid
      therapy died because of a meningoencephalitis related to a severe
      immunosuppression. CONCLUSIONS: Treatment of vascular anomalies during childhood
      need an early accurate diagnosis. If a right therapeutic sequence is not
      performed, useful drugs can turn into inefficient or dangerous. Most treatment
      complications in these patients can be avoided.

PMID- 14677355
TI  - [Prognostic factors in pediatric liver transplantation. Multivariate analysis].
AB  - AIM: To analyze independent risk factors associated with poor graft and patient
      survival in a series of 292 pediatric liver transplants (PLT) performed in 234
      children during a 15 years period. MATERIAL AND METHODS. 1. Univariate graft and
      patient survival analysis in 45 variables related to pretransplant patient
      status, surgical technique and donor conditions. 2. Variables found with
      univariate analysis to be associated with outcome were entered into a stepwise
      backward proportional hazard model (Cox), to determine independent prediction of
      outcome. RESULTS: 11 variables influence the graft survival: recipient age, z
      score recipient height, UNOS status, recipient and donor weight, transplant for
      immune hepatitis, platelet transfusion during the transplant, blood index > 4
      during the surgery, type of arterial reconstruction, retransplantation and era of
      the transplant (first er: 1986-1990; 2nd. era: 1991-1995; 3rd. era: 1996-2000).
      Four of those variables are independent in the multivariate analysis: UNOS 1
      status (Odds Ratio, OR = 2.82, 95% confidence interval = 1.36-5.85), recipient <
      3 years (OR = 3.76, 95% CI = 2.13-6.63), transplants for autoimmune hepatitis and
      era (OR of first and second versus third era respectively 3.93 and 2.81). The
      independent variables influencing the patient survival were: children receiving
      more than one graft children less than 3 years old and transplant era.
      CONCLUSIONS: Liver transplant in small children is associated with an increased
      risk of graft loss and patient dead. The experience of the hospital in pediatric
      liver transplantation improves the results, particularly in small children.

PMID- 14677356
TI  - [In which patients is the oxybutynin-desmopressin combination therapy
      indicated?].
AB  - PURPOSE: We assume that desmopressin decreases nocturnal urine output of the
      enuretic child. The aim of this study is to evaluate the efficacy of desmopressin
      plus oxybutynin and to define urodynamic pattern in children with bladder
      hyperactivity partially-responders to oxybutynin alone (in which nocturnal
      enuresis persists in spite of bladder stability). METHODS: 48 enuretic patients
      with urodynamically confirmed bladder hyperactivity were enrolled in the
      prospective study. All patients were treated with oxybutynin, 0.3-05 mg/Kg/day
      orally, and bladder therapy, for six months. At the end of this period, patients
      with excellent response (cessation of nocturnal and diurnal symptoms) was
      designed as group I (28 children, 58%); patients with partial response
      (persistence of nocturnal enuresis) as group II (19 children, 40%); and patients
      non-responders as group III (1 patient, excluded because of no completion of
      treatment). After six months patients were assessed by standardized urodynamic
      study. Group II patients were treated with combined therapy, desmopressin-20
      mcg/day-plus oxybutynin, for six months. Group I patients served as controls.
      RESULTS: The differences between mean bladder accommodation and mean voiding
      pressure in patients with excellent response and partially response to oxybutynin
      were statistically significant. After combined therapy 18 of 19 patients (95%) of
      group II became group I. CONCLUSIONS: The efficacy of desmopressin plus
      oxybutynin is confirmed in patients with low final accommodation (< 3 ml/cm H2O)
      and high voiding pressure (> 70 cm H2O). Combined therapy can be a good choice of
      treatment in children with bladder hyperactivity with partial response to
      oxybutynin alone.

PMID- 14677357
TI  - [Surgical treatment of cholelithiasis in children. Role of cholecystotomy].
AB  - Cholelithiasis is a rare pathology in children and with a different etiology,
      composition and clinic than adult. Cholecystectomy is the standardized treatment.
      The cholecystectomy is an alternative treatment in childhood. We studied 30
      patients, aged between 8 months and 13 years, 15 of them with cholecystectomy and
      15 with removal of pigment gallstones. The patients were followed up for 3 months
      11 years. Recurrent stone formation was noted in one patient. 14 of the patients
      were non-symptomatic with normal ecography controls.

PMID- 14677358
TI  - [Retroperitoneoscopy: minimally invasive renal surgery].
AB  - OBJECTIVE: Retroperitoneal laparoscopy is well known as a surgical technique in
      adult patients. Its use in pediatric surgery is still-recent but, because of the
      good results, retroperitoncoscopy indications are getting more acceptance and
      widening indications. The aim of this work is to analyze our initial experience
      in retroperitoneal laparoscopy procedures in urological diseases at our centre.
      PATIENTS AND METHODS: From July 2001 to February 2002 retroperitoneal laparoscopy
      has been used in 6 patients aged 6 months to 14 years. Surgical indications were:
      pyelolithotomy (lithiasis non-subsidiary to extracorporeal shock wave lithotripsy
      (n = 1); nephrectomy ofmulticystic dysplastic kidney (n = 4); and nephrectomy of
      atrophicpelvic kidney (n = 1). RESULTS: Mean operative time in nephrectomy has
      been 102 minutes, and 230 minutes in conservative surgery. All 5 patients
      nephrectomized were discharged 24 hours after operation with no postoperatory
      incidences. The patient operated on for pyelolithiasis (in which a external
      drainageand a pyelouretheral stent (pig-tail) was placed) remained one week until
      he could be discharged without drainage. The pig-tail stent was thrown out
      spontaneously three weeks later through the urethra. Follow up demonstrated no
      stenosis in this case and no complications in nephrectomy patients. CONCLUSION:
      Retroperitoneal laparoscopy is effective and safe in renal surgery and surpasses
      transperitoneal laparoscopy because its safety in reconstructive surgery avoiding
      urine leakage risk into the abdomen.

PMID- 14677359
TI  - [Severe epispadias: the Mitchell's technique].
AB  - Epispadias associated or not to bladder extrophy is a congenital malformation
      with a difficult surgical correction. Mitchell published his technique in 1996,
      and it's based in the complete dissection of the uretheral band, ventral peneal
      skin and both corporas including their proximal insertion, that in next steps
      will be separated in all the length. These manoeuvres permit to: 1) Correct the
      dorsal incurvation; 2) Locate the urethra in a ventral position; 3) Locate the
      meatus at the tip of the penis with a vertical orientation. MATERIAL AND METHODS:
      We have performed these surgical procedure in 6 patients, 4 of them were
      epispadias (a 23 years old patient who had there surgical procedure, with
      persistent incurvation), the others two were associated with bladder extrophy, 3
      had hormonal treatment previous surgery, due to a hypoplastic penis. In the two
      patients with bladder extrophy we used a labial mucosa graft sutured to the
      tubularized urethral plate to relocate the meatus at the tip of the penis.
      RESULTS: The esthetic results were good in all cases, 2 had a fistula that was
      corrected surgically.

PMID- 14677360
TI  - [Nasal neuroglial heterotopy in children].
AB  - Nasal gliomas are tumors of extracranial neuroglial tissue. The incidence is very
      low, with little more than 300 cases described unliterature. It is important to
      make a correct diagnosis study of this lesion, to avoid the possible
      complications derived from an erroneous treatment. We review a case of one girl
      with midline nasal tumor, she was operated on with total extirpation of the
      tumor, we analyze the previous diagnosis study and their histopathology.

PMID- 14677361
TI  - [Conservative surgery of ovarian torsion in pediatrics].
AB  - The authors describe the case of two girls diagnosed of ovarian torsion secondary
      to a cyst. They were operated on by conservative ovarian therapy regardless the
      time of evolution and ovary macroscopical aspect. These 2 patients were 9 and 13
      years old, with abdominal colic pain of 48 and 36 hours of evolution. The
      diagnosis by doppler sonography was ovarian torsion, with a 4 cms cyst in the
      right ovary in the first case and a 5 cms cyst in the left ovary in the second
      patient. Both patients were operated on. After untwisting the ovary, we instille
      warm saline solution to this ovary and, after waiting for 10 minutes, we resect
      the ovarian cyst and it recuperates partial and heterogeneous its pink colour. We
      advise to the family about the possibility of surgical reintervention if the
      ovary is not viable. After 10 and 12 days of surgical intervention, the Doppler
      sonography has confirmed the existence of ovary flow and the symmetry of affected
      ovary in comparation to the opposite on. At the present, both patients are
      asymptomatic, with exhaustive ultrasound controls. Ovarian torsion is the most
      frequent complication of ovarian tumours of pediatrics (3-16%) and this is a real
      emergency in gynecology. Traditionally, it has been recommended the exeresis of
      ovarian torsion. Regardless the blue aspect of isquemic ovary affected by torsion
      and the time of evolution, in our experience when there is a minimal possibility
      of ovarian viability, it is possible to follow a conservative therapy because the
      macroscopical aspect of the ovary is not necessarily related with the following
      evolution of the case.

PMID- 14677362
TI  - [Nephrogenic adenoma of the urethra. Report of a case].
AB  - Nephrogenic adenoma is a benign urothelial neoformation rare in children. It can
      be present in the entire urinary tract, being more common in the bladder and very
      infrequent in urethra. These metaplasic changes seem to be due to irritative
      stimulus to the epithelium, including lithiasis, previous surgery, permanent or
      repeated catheterization, infective diseases and chemotherapy and or
      radiotherapy. The diagnosis is established after biopsy and in most of the cases
      the treatment of choice consists of transurethral resection of the lesion. We
      report the case of a boy 11 years old who was diagnosed of Nephrogenic adenoma of
      prostatic urethra after cistoscopy for repetitive urethremorrhagia. The patient
      was managed conservatively and oral antibiotic therapy was administered being the
      patient asymptomatic and free of recurrence during the follow up.

PMID- 14677363
TI  - The amphibole hypothesis--a nested case-control study of lung cancer and exposure
      to chrysotile and amphiboles.
AB  - This paper describes a case control study investigating separately the lung
      cancer risk of exposure to chrysotile and to amphiboles. Logistic regression
      models were used to estimate separate exposure-response curves for the two fibre
      types, controlling for smoking. In the period longer than 15 years before lung
      cancer diagnosis, smokers above the 90th percentile of cumulative exposure to
      either chrysotile (OR = 1.8, 95% CI = 0.6-5.2) or amphibole (OR = 2.3, 95% CI =
      0.9-6.2) had a somewhat higher risk than those with lower exposure. The author
      found suggestive evidence of an association between chrysotile and lung cancer,
      and especially between amphiboles and lung cancer. In this study, cumulative
      exposures to amphiboles were on average 40 times lower than cumulative exposures
      to chrysotile, and the author assumes that the amphibole effect would be much
      higher if the amphibole level of cumulative exposure were the same as that of
      chrysotile.

PMID- 14677364
TI  - Behavioural response in paired food choice experiments with Oniscus asellus
      (Crustacea, Isopoda) as an indicator of different food quality.
AB  - This paper describes a study of behavioural response in terrestrial isopod
      Oniscus asellus when offered two food pellets of different quality. One group had
      a choice of sterilised food and food pellets covered with mould. The other group
      had a choice of uncontaminated and cadmium-dosed food. During the behavioural
      test, the animals were monitored by a video camera and each visit to food pellets
      and time spent around it was counted. The results show that animals spent
      significantly less time near sterilised and cadmium-dosed food than with
      uncontaminated or mould-covered food. Discrimination between offered food pellets
      showed that avoidance behaviour can be used as an indicator of different food
      quality.

PMID- 14677365
TI  - Inhibition of acetylcholinesterase activity in the terrestrial isopod Porcellio
      scaber as a biomarker of organophosphorus compounds in food.
AB  - This paper describes the toxicity of organophosphorus pesticide diazinon in
      juvenile and adult terrestrial isopods Porcellio scaber (Isopoda, Crustacea). The
      woodlice were exposed to different concentrations of diazinon added to food (5,
      10, 50, and 100 or 150 micrograms/g dry food). Weight change and food
      assimilation efficiency were determined two and four weeks after the exposure.
      The activity of acetylcholinesterase (AChE) in surviving animals was measured at
      the end of the experiment. The results show that woodlice exposed to diazinon do
      not significantly differ from controls in growth and feeding rate. The reduction
      of AChE activity was observed at the lowest diazinon exposure (5 and 10
      micrograms/g dry food). These results suggest that AChE activity might prove a
      useful biomarker, indicating low levels of organophosphates in food.

PMID- 14677366
TI  - Comparison of diethylene glycol and phenol biodegradability by different test
      methods.
AB  - Biodegradation is generally recognised as an important removal mechanism for
      pollutants in natural ecosystems. It determines the concentration of substances
      in the environment. According to the legislation of the European Union, there are
      three levels for biodegradability testing protocols for chemicals which cover
      different test conditions. This paper describes one such multilevel approach to
      biodegradation testing. Four different tests were performed on diethylene glycol
      and phenol. Diethylene glycol did not fulfill the requirements for ready
      biodegradable substances, while it degraded well in wastewater treatment plant
      simulation test. Phenol in turn, resulted ready biodegradable, and its
      biodegradability depended less on experimental conditions than the
      biodegradability of diethylene glycol. This corroborates the importance of
      combining different test methods to obtain relevant biodegradability data.

PMID- 14677367
TI  - Photothermal bioanalytical methods for pesticide toxicity testing.
AB  - This paper describes bioanalytical methods and biosensors which rely on
      cholinesterase (ChE) inhibition and can be used to detect and test the toxicity
      of organophosphate (OP) and carbamate pesticides. Particular attention is given
      to the combined use of these methods and photothermal detection that has recently
      led to improved sensitivity and increased sample throughput of ChE bioanalytical
      assay. Following a rapid and simple sample preparation procedure, this assay can
      detect organophosphate pesticides such as paraoxon in the sub ng/mL concentration
      range. The AChE bioanalytical method demonstrated different sensitivity to
      various pesticides, which correlated well with pesticide toxicity expressed as
      LD50 for rats. Similarly, the same pesticide yielded different ChE inhibition in
      different organisms. This opens the possibility of applying these bioanalytical
      methods to evaluate the acute toxicity of OP compounds or of environmental
      samples to particular organisms.

PMID- 14677368
TI  - Aquatic toxicity of selected chemicals as a basic criterion for environmental
      classification.
AB  - In order to protect public health and the environment, the EU legislation has
      proposed a classification of dangerous substances. Chemicals are classified
      according to physico-chemical as well as toxicological and ecotoxicological
      properties. Environmental classification is based on inherent harmful potential
      of a substance to organisms and on its environmental fate, that is, degradation
      and bioaccumulation potential. In this study, experimental data on acute and
      chronic toxicity to aquatic organisms and biodegradability and bioaccumulation
      data obtained from literature were used to classify arsenic (applied as As2O3),
      copper (applied as CuCl2), phenol and 1,4-butynediol. For this purpose, the "base
      set data" obtained from standardised test methods served as a convenient
      indicator of the inherent toxicity of tested chemicals. Additional data about
      environmentally relevant properties of arsenic and 1,4-butynediol could lead to a
      revision of present chemical classification and labelling.

PMID- 14677370
TI  - Synthesis and anticonvulsant activity of some new dioxolane derivatives.
AB  - In this study, ten 2-acetylnaphthalene derivatives with a dioxolane structure
      were synthesized and screened for their anticonvulsant activities. Dioxolane
      derivatives were prepared by the reaction with appropriate ethanone, glycol and p
      toluensulphonic acid. The structures of the compounds were elucidated by IR, 1H
      NMR and elemental analysis. Anticonvulsant activities of the compounds were
      determined by maximal electroshock seizure (MES) test and subcutaneous metrazol
      (ScMet.) test. The rotarod toxicity test was used for the assessment of
      neurological deficits. According to the activity studies compound 6 was found
      neurotoxic, compounds, 1, 4, 5, 7-9 were found protective against MES and 7-10
      were found protective against ScMet. Compounds 2 and 3 were found inactive.

PMID- 14677369
TI  - Synthesis and docking studies of alkylene-linked dimers of (-)-huperzine A.
AB  - (-)-Huperzine A (5, HupA), an alkaloid isolated from the herb Huperzia serrata,
      is a potent, selective and reversible acetylcholinesterase (AchE) inhibitor.
      Based on the hypothesis with respect to two binding sites in the active gorge of
      AChE and the good example of bis-tacrine, it was predicted from the docking
      studies of alkylene-linked dimers of HupA that dimers 6 (n = 5, 7, 9) might have
      good AChE inhibitory activity. Therefore, six dimers with 7-12 methylene units as
      tethers were thus prepared. It was found that these dimers were less potent than
      HupA in inhibition of AChE. The difference of the inhibitory potency between
      these dimers is coincident with the results of the docking studies.

PMID- 14677371
TI  - Validated high performance liquid chromatographic method for simultaneous
      determination of phenytoin, phenobarbital and carbamazepine in human serum.
AB  - A high performance liquid chromatographic (HPLC) method for the simultaneous
      determination of phenytoin (CAS 57-41-0), phenobarbital (CAS 50-06-6,
      phenobarbitone) and carbamazepine (CAS 298-46-4) is described. The serum was
      extracted with ethyl acetate, the dried extract was reconstituted in mobile phase
      and the aliquot was injected. The eluent drugs were detected at 230 nm. The
      mobile phase consisting of methanol: water: glacial acetic acid mixture (67:33:1,
      v/v/v) was used at a flow rate of 1 ml/min on C-18 column. The absolute recovery
      was above 96% of all the three drugs over a concentration range of 0.5-50.0
      micrograms/ml. The inter-day and intra-day precision relative standard deviation
      (RSD) ranged from 0.79-5.13% and 0.11-6.81%, respectively. The method is simple,
      rapid, accurate and sensitive and is presently used for therapeutic drug
      monitoring in epileptic patients. The results obtained with this method showed
      very good clinical correlation.

PMID- 14677372
TI  - Single dose pharmacokinetics of alpha-dihydroergocryptine in patients with
      moderate to severe renal insufficiency.
AB  - AIM: This study was carried out to evaluate the pharmacokinetic profile of alpha
      dihydroergocryptine (CAS 14271-05-7, DHEC, Almirid) in plasma and urine in
      patients with moderately to severely impaired renal function (creatinine
      clearance < 30 ml.min-1.1.73 m-2), following administration of single oral doses.
      METHODS: This was an open, nonrandomized trial. Seven patients with chronic renal
      disease and six healthy subjects received a single dose of 20 mg DHEC. Blood and
      urine samples were taken at specified intervals up to 72 h after dosing.
      Concentrations of unchanged DHEC were determined by radio-immunoassay (RIA) and
      concentrations of unchanged DHEC plus pooled metabolites by enzyme-immunoassay
      (EIA), respectively. RESULTS: In patients with impaired renal function, the mean
      Cmax and AUC(0-infinity) values for unchanged DHEC were 2.1 (95% confidence
      interval CI: 0.99 to 4.42) and 1.85 (95% CI: 0.72 to 4.77) times larger than in
      controls. The 24-h urinary excretion was only 0.3 (95% CI: 0.12 to 0.71) times
      that in healthy subjects. Similar findings were recorded for total DHEC plus
      metabolites. CONCLUSIONS: As treatment with DHEC is in general uptitrated
      starting with doses as low as 5 mg DHEC, which are then increased while
      accounting for individual effects both in terms of efficacy and tolerability, the
      observed range of effects of impaired renal function on DHEC's pharmacokinetics
      does not suggest the need to revise this policy, although lower end-doses are
      likely to be achieved.

PMID- 14677373
TI  - Synthesis of the butanamide derivative S 19812, a new dual inhibitor of
      cyclooxygenase and lipoxygenase pathways.
AB  - The general synthetic pathway and the interactions with arachidonic acid
      metabolism of the new compound S 19812 (N-hydroxy-N-methyl 4-(2,3-bis-(4
      methoxyphenyl)-thiophen-5-yl)butanamide, CAS 181308-68-9) were investigated. S
      19812 was selected for its well balanced dual inhibition of cyclooxygenase and 5
      lipoxygenase pathways in vitro in rat polymorphonuclear neutrophils (PMNs) (IC50
      PGE2: 0.10 mumol/l, LTB4: 0.07 mumol/l) and ex vivo in mice blood (ED50 PGE2:
      13.1 mg/kg, LTB4: 20.8 mg/kg). These properties make this drug a promising
      therapeutic agent for pain and inflammation associated with osteoarthritis.

PMID- 14677374
TI  - Synthesis, antioxidant and antiinflammatory activity of novel aryla-cetic and
      aryl-hydroxamic acids.
AB  - Four new aryl-acetic acids and the corresponding hydroxamic acids were
      synthesized. These compounds showed interesting interaction with the free radical
      1,1-diphenyl-2-picryl-hydrazyl (DPPH), scavenging activity on .OH, inhibition of
      soybean lipoxygenase and a significant inhibition of carrageenin induced paw
      edema in rats (44.1-70.9%) at a concentration of 0.01 mmol/100 g.

PMID- 14677375
TI  - Bioavailability of two dermal formulations of S(+)ibuprofen in rabbit.
AB  - Ibuprofen (CAS 15687-27-1) is widely used in painful situations and, usually, is
      administered in the racemic form. Since enantiomers may exert different
      pharmacodinamic and pharmacokinetic effects, the pharmaceutical industry has
      placed new emphasis on the preparation of new formulations of enantiomerically
      pure drugs that must be pharmacokinetically characterised prior to their
      administration in human beings. In this study, the absorption kinetics of two
      topical formulations of S(+)ibuprofen in rabbits was investigated. The
      S(+)ibuprofen levels in rabbit plasma were determined by a non-chiral HPLC
      method, whereas the absence of the R(-)ibuprofen enantiomer in plasma was
      confirmed by a chiral HPLC method. The results showed that S(+)ibuprofen was
      absorbed through the rabbit skin upon administration and the obtained levels
      varied with the formulation.

PMID- 14677376
TI  - Conformational aspects of human formyl-peptide receptor agonists.
AB  - The conformation of several Met-Ile-Phe-Leu analogues was analyzed using circular
      dichroism and infra-red absorption. Their effect on human neutrophils was
      verified by receptor binding assays and measurements of lysozyme release. The
      results demonstrate that in amphipatic environments the compounds examined can be
      highly and weakly ordered in beta-turn structures, in dependence on their N
      terminal substituents. The ability of the compounds to evoke neutrophil functions
      appears strongly and weakly influenced by N- and C-terminal modification,
      respectively.

PMID- 14677377
TI  - Background physics for magnetic stimulation.

PMID- 14677379
TI  - The triple stimulation technique to study corticospinal conduction.

PMID- 14677378
TI  - TMS and threshold hunting.

PMID- 14677380
TI  - Pulse configuration and rTMS efficacy: a review of clinical studies.

PMID- 14677381
TI  - Interleaving fMRI and rTMS.

PMID- 14677382
TI  - Is functional magnetic resonance imaging capable of mapping transcranial magnetic
      cortex stimulation?

PMID- 14677383
TI  - Applications of combined TMS-PET studies in clinical and basic research.

PMID- 14677384
TI  - A coil for magnetic stimulation of the macaque monkey brain.

PMID- 14677385
TI  - Neurophysiological characterization of magnetic seizure therapy (MST) in non
      human primates.

PMID- 14677386
TI  - rTMS as treatment strategy in psychiatric disorders--neurobiological concepts.

PMID- 14677387
TI  - Motor cortical and other cortical interneuronal networks that generate very high
      frequency waves.
AB  - A remarkable feature of motor cortical organization in higher mammals is that a
      brief electrical stimulus elicits in the pyramidal tract and corticospinal tract
      an unrelayed direct (D) wave followed by multiple indirect (I) waves at
      frequencies as high as 500-700 Hz. This review presents some conclusions
      regarding very high frequency synchronous activity in mammalian cortex: (1)
      Synchrony in repetitive I discharges is extraordinary in humans and monkeys, less
      in cats and still less in rats, being there represented by a delayed broad wave;
      such phylogenetic trends have important implications for the suitability of lower
      mammalian species for studies of high frequency cortical networks in the human
      brain; (2) The evidence from microstimulation at different cortical depths and
      pial cooling favors a vertically oriented chain of interneurons that
      centripetally excite corticospinal neurons as the basis for inter-I wave
      periodicity and synchrony; (3) Significantly, the I wave periodicity is conserved
      despite wide changes in stimulus parameters; (4) Synchronous high frequency
      activity similar to that of I waves can be recorded from other neocortical areas
      such as visual and somatosensory cortex; however, evidence is still lacking that
      the output neurons of these cortical regions have synchronized discharges
      comparable to I waves; (5) In limbic cortices, the frequency of synchronous
      neural activity is lower than that in motor cortex or related cortices and
      periodicity is not conserved with changes in stimulus parameters, indicating a
      lack of the neocortical interneuronal substrate in limbic cortex; (6) We propose
      that the very high frequency synchronous activity of motor cortical output
      reflects a computational function such as a "clock," quantizing times at which
      inputs would interact preferentially yielding synchronous output discharges. Such
      circuitry, if a general feature of neocortex, would facilitate rapid
      communication of significant computations between cortical regions.

PMID- 14677388
TI  - Generation of I waves in the human: spinal recordings.

PMID- 14677389
TI  - Surround inhibition.

PMID- 14677390
TI  - Functional connectivity of the human premotor and motor cortex explored with TMS.

PMID- 14677391
TI  - Inhibitory control of acquired motor programs in the human brain.

PMID- 14677392
TI  - Motor control in mirror movements: studies with transcranial magnetic
      stimulation.

PMID- 14677393
TI  - Impact of interhemispheric inhibition on excitability of the non-lesioned motor
      cortex after acute stroke.

PMID- 14677394
TI  - Disruption of the neural correlates of working memory using high- and low
      frequency repetitive transcranial magnetic stimulation: a negative study.

PMID- 14677395
TI  - Motor and phosphene thresholds: consequences of cortical anisotropy.

PMID- 14677396
TI  - The organisation and re-organisation of human swallowing motor cortex.

PMID- 14677397
TI  - Exploring paradoxical functional facilitation with TMS.

PMID- 14677398
TI  - Repetitive magnetic and functional electrical stimulation reduce spastic tone
      increase in patients with spinal cord injury.

PMID- 14677399
TI  - Pharmacology of TMS.
AB  - Testing the effects of CNS active drugs (neurotransmitters, neuromodulators) on
      motor cortical excitability by means of TMS has developed into an important field
      of research. At least two major avenues can be followed up. First, testing a drug
      with a known singular mode of action may provide information on the physiological
      properties of a novel TMS measure. For instance, it was shown that the recently
      discovered short latency afferent inhibition was significantly reduced by the
      anticholinergic (M1 antagonist) scopolamine (Di Lazzaro et al., 2000b). This
      opened up the opportunity to use short latency afferent inhibition (SLAI) to
      detect deficiency of central cholinergic innervation in neurological disease, for
      instance in Alzheimer's disease (Di Lazzaro et al., 2002). The other avenue is to
      use an array of well characterised TMS measures to obtain knowledge about the
      modes of action at the systems level of human cortex of a drug with unknown or
      multiple modes of action. One example is the novel anticonvulsant topiramate for
      which multiple modes of action were identified in animal experiments, including
      blocking effects on voltage-gated sodium channels, positive modulation of the
      GABAA receptor, inhibition of the kainate and AMPA subtypes of the glutamate
      receptor, inhibition of L-type voltage-gated calcium channels, and increase of
      cerebral GABA levels. Topiramate resulted in a selective increase of SICI and
      decrease of ICF without affecting motor threshold or CSP (Reis et al., 2002).
      From these results it was concluded that the main modes of action of topiramate
      at the level of the human motor cortex are its enhancing action on GABAA
      receptors and/or inhibition of glutamate receptors. TMS offers now a wide array
      of measures of motor cortical excitability which covers many different forms of
      excitability, such as axon and inhibitory and excitatory synaptic excitability.
      Increasing numbers of different forms of cortical inhibition are being
      discovered, such as SICI (GABAA dependent), CSP (GABAB dependent) and SLAI
      (cholinergic), and it is very likely that more will follow soon.

PMID- 14677400
TI  - Bihemispheric plasticity after acute hand deafferentation.

PMID- 14677401
TI  - Modulation of use-dependent plasticity by D-amphetamine.

PMID- 14677402
TI  - Transcranial direct current stimulation (tDCS).
AB  - tDCS appears to be a promising tool in neuroplasticity research with some
      tentative perspectives in clinical neurophysiology. The next steps to be carried
      out encompass better histological safety data. In order to preclude the
      possibility of neuronal damage, extending tDCS duration should be limited until
      more direct safety criteria are available than those derived from Agnew and
      McCreery (1987) (cf. Nitsche et al, this volume). Safe stimulation protocols have
      to be developed which allow an extension of the duration of after-effects towards
      a somewhat permanent state, supposing a beneficial effect can be found in
      neurological diseases or in neurorehabilitation.

PMID- 14677403
TI  - Modulation of cortical excitability by weak direct current stimulation-
      technical, safety and functional aspects.

PMID- 14677404
TI  - Modulation of motor consolidation by external DC stimulation.

PMID- 14677405
TI  - Pharmacology of transcranial direct current stimulation: missing effect of
      riluzole.

PMID- 14677406
TI  - Transcranial magnetic and direct current stimulation of the visual cortex.

PMID- 14677407
TI  - Neural correlates of phosphene perception.

PMID- 14677408
TI  - The causal role of the prefrontal cortex in episodic memory as demonstrated with
      rTMS.

PMID- 14677409
TI  - The parietal cortex in visual search: a visuomotor hypothesis.

PMID- 14677410
TI  - Effects of repetitive transcranial magnetic stimulation (rTMS) on slow cortical
      potentials (SCP).

PMID- 14677412
TI  - Modulation of sensorimotor performances and cognition abilities induced by RPMS:
      clinical and experimental investigations.
AB  - The investigations presented in this chapter lead to the conclusion that
      proprioceptive afferent inflow to the CNS induced by RPMS elicits various
      modulatory effects in sensorimotor and cognitive systems. Since the build-up of
      the conditioning effects is delayed and the effects itself are long-lasting, it
      has to be assumed that these effects are caused via neuromodulators. Therefore,
      the presented approach is promising to improve sensorimotor and cognitive
      disturbances after lesions in the CNS, e.g. after a stroke, by facilitation of
      reorganization.

PMID- 14677411
TI  - Transcranial magnetic stimulation in brainstem lesions and lesions of the cranial
      nerves.

PMID- 14677413
TI  - TMS in stroke.

PMID- 14677414
TI  - Cortical silent period is shortened in restless legs syndrome independently from
      circadian rhythm.

PMID- 14677415
TI  - Repetitive magnetic stimulation for the treatment of chronic pain conditions.

PMID- 14677416
TI  - Fluctuations of motor cortex excitability in pain syndromes.

PMID- 14677417
TI  - Can epilepsies be improved by repetitive transcranial magnetic stimulation?-
      interim analysis of a controlled study.

PMID- 14677418
TI  - Prefrontal cortex stimulation as antidepressant treatment: mode of action and
      clinical effectiveness of rTMS.

PMID- 14677419
TI  - Motorcortical excitability after electroconvulsive therapy in patients with major
      depressive disorder.

PMID- 14677420
TI  - Transcranial magnetic brain stimulation and the cerebellum.

PMID- 14677421
TI  - On the proposed reformation of university professorship in Italy.

PMID- 14677422
TI  - The origin of dystrophin-glycoprotein complex(DGC)-related muscular dystrophies:
      the need for protection against an ancestral pathogen?
AB  - Because of its crucial role during the early stages of morphogenesis, no genetic
      defects associated to dystroglycan have been reported so far. Dystroglycan is an
      important member of the dystrophin-glycoprotein complex (DGC) and in several
      muscular dystrophies, depending on abnormalities of proteins belonging to or
      associated with the DGC, it is frequently observed a significant reduction of
      dystroglycan levels at the sarcolemma. Recently, it has been demonstrated that
      dystroglycan acts as a receptor for pathogens such as M. leprae and arenaviruses.
      It is well-known that mutated alleles causing diseases can be selected in order
      to confer an additional genetic advantage. Herein it is discussed the possibility
      that mutations leading to a certain number of muscular dystrophies might have
      been originally selected to indirectly gain a specific advantage: the absence or
      the lower levels of dystroglycan could have greatly reduced the risk of some
      ancestral lethal infections specifically directed against muscles.

PMID- 14677423
TI  - Aminoacid profile and oxidative status in children affected by Down syndrome
      before and after supplementary nutritional treatment.
AB  - Down syndrome is the most common autosomal aberration among liveborns,
      characterised by several clinical features and metabolic disturbances. Aminoacid
      pathways abnormalities and defective oxidative balance are the most common
      metabolic problems in Down Syndrome. To evaluate the biochemical responses of
      children with Down Syndrome to a nutritional regimen supplemented with
      aminoacids, vitamins and polyunsaturated fatty acids, we submitted 86 subjects
      divided in two groups (0-6 and 6-12 years) to the dosage of plasma levels of
      aminoacids, antioxidant enzymes activities and reactive oxygen species, before
      and after 12 months of such nutritional supplementation and in relation to normal
      controls. The results obtained showed a tendency towards the values of normal
      subjects with statistically significant differences. Although other studies must
      be performed to confirm and define such report, our experience supports the
      usefulness of a nutritional supplementation with aminoacids, vitamins and
      polyunsaturated fatty acids, also considering the absence of side effects.

PMID- 14677424
TI  - Biochemical characterization of human brain and kidney tissues by magnetic
      resonance spectroscopy.
AB  - In vivo and in vitro Magnetic Resonance Spectroscopy is useful for monitoring
      changes in intracellular metabolites of human cerebral and renal tissues. Healthy
      and tumoral tissues of different histologic types have been characterized from a
      biochemical point of view. In vitro molecular characterization is performed on
      both the aqueous and lipid extracts of surgically removed tissue biopsies, after
      in vivo MRS, yielding a full picture of tissue biochemistry. Biochemical markers
      of healthy brain and kidney and of their relative neoplastic lesions have been
      disclosed. Moreover, some biochemical features can differentiate neoplasm within
      the same histological type. Ex vivo MRS also gives molecular information related
      to necrotic phenomena in glial tumors. MRS finding paralleled histologic data and
      new knowledge about the molecular base of proliferative neoplastic phenomena can
      be obtained.

PMID- 14677425
TI  - Vibrational characterisation and biological activity of carnosine and its metal
      complexes.
AB  - The spectroscopic characterisation of free carnosine and its coordination
      compounds with Cu(II), Zn(II) and Co(II) ions are discussed. Raman and IR studies
      on metal-carnosine systems have been performed, obtaining a relationship between
      the vibrational spectra and the structure of the predominant species formed. The
      biological activity of free carnosine and of its complexes is briefly considered.

PMID- 14677426
TI  - Imaging transcription complexes with the Atomic Force Microscope.
AB  - Recent developments in sample deposition and image analysis have shown that the
      Atomic Force Microscope is a valuable tool for the structural investigation of
      transcription complexes. When deposited under conditions that allow molecular
      equilibration onto the substrate, transcription complexes behave as worm-like
      chains and the mean square end-to-end distance can readily be used to determine
      the protein induced DNA bend angle. Measurements of the DNA contour length by
      means of accurate image processing procedures have revealed a DNA compaction in
      transcription complexes which is compatible with wrapping of the DNA against the
      surface of the RNA Polymerase. The methods presented have to be considered of
      general practical use for imaging protein-DNA complexes.

PMID- 14677427
TI  - Oogenesis in Drosophila melanogaster: a model system for studying cell
      differentiation and development.
AB  - Drosophila oogenesis is a complex developmental process involving the coordinated
      differentiation of germ line and somatic cells. Correct execution and timing of
      cell fate specification and patterning events is achieved during this process by
      the integration of different cell-cell signalling pathways, eventually leading to
      the generation of positional information inside the oocyte, that is instrumental
      for the establishment of embryonic polarity. The large body of data accumulated
      at both cellular and molecular levels in the last decade clearly demonstrated how
      Drosophila oogenesis is a genetically tractable system particularly suited for
      the investigation of key developmental biology questions. Our recent contribution
      to the field relies on the characterisation of three different mutants named
      tegamino (teg), hold hup (hup) and tulipano (tip), identifying novel gene
      functions required during oogenesis. Specifically, teg is implicated in the
      morphogenesis of the follicular epithelium surrounding the germ line cells in the
      egg chamber, hup is involved in the establishment of egg chamber polarity and tip
      in the regulation of the dynamic germ cell chromatin organisation.

PMID- 14677428
TI  - Apoptosis meets proteasome, an invaluable therapeutic target of anticancer drugs.
AB  - This report reviews the current status of extensive efforts directed towards the
      interpretation of crosstalk between apoptosis and proteasome to understanding the
      molecular mechanism of anticancer agents targeting proteasome, with particular
      focus on MG132 and PS-341. The discovery that all cancer cells have retained the
      apoptotic death program has offered to the researchers new biochemical targets to
      design anticancer drugs. Moreover, the demonstration that proteasome inhibition
      induces apoptosis and sensitizes cancer cells to traditional tumoricidal agents
      has proposed the proteasome as an attractive target for development of new
      anticancer drugs. Since then, a number of both naturally occurring and synthetic
      inhibitors of the proteasome have been identified. The best characterized and
      most widely used inhibitors of the proteasome are the peptide aldehydes; among
      these MG132, due to its broad spectrum of action, low cost and rapid
      reversibility of action, still remains the first choice to study proteasome
      function in cell and tissue cultures. Recently, a very potent new class of
      selective and reversible proteasome inhibitors which contains an inhibitory
      boronate group has been described. PS-341 represent the first of this promising
      class of agents that could have application in cancer therapy and it is the only
      that has progressed to clinical trials.

PMID- 14677429
TI  - Locked down: preserving hospital security. Trends are level, but facilities
      remain violence-prone.

PMID- 14677430
TI  - The path to peerless peer review. Due process key to avoiding physician
      litigation.

PMID- 14677431
TI  - 2002 Congress of Neurological Surgeons presidential address.

PMID- 14677432
TI  - From discovery to design: image-guided surgery.

PMID- 14677433
TI  - Endovascular neurosurgery: an evolution in process.

PMID- 14677434
TI  - Discovering the novel surgical approach.
AB  - Discovering the novel surgical approach requires surgeons to look beyond the
      dogma of current practices. By applying simple principles and concepts, such as
      the two-point method, working depth, working area, and angle of attack, novel
      approaches can evolve from existing approaches to improve exposure and decrease
      patient morbidity. The EOZ and ELSI are two examples in which these principles
      have been applied to generate novel surgical approaches by modifying existing
      ones. Compared to the previously used approaches, both of these novel approaches
      afford superior access to their respective regions of the brain stem with
      decreased rates of morbidity.

PMID- 14677435
TI  - Honored guest presentation: discovery of the spine specialist: instrumentation of
      the cervical spine.

PMID- 14677436
TI  - The neurosurgeon as a spine surgeon: an historical perspective.

PMID- 14677437
TI  - The essentials of spine biomechanics for the general neurosurgeon.

PMID- 14677438
TI  - Honored guest presentation: leading the future of spinal surgery.

PMID- 14677439
TI  - Prosthetics and biologics: the wave of the future.

PMID- 14677440
TI  - Minimalism: is less more?

PMID- 14677441
TI  - Spinal deformity: the role of the neurosurgeon.

PMID- 14677442
TI  - Development of evidence-based guidelines for the management of acute spine and
      spinal cord injuries.

PMID- 14677443
TI  - Freedom to expand the neurosurgeon's domain: the modern neurovascular team.

PMID- 14677444
TI  - Shunt technology: contemporary concepts and prospects.

PMID- 14677445
TI  - Modern paradigms of pain management.

PMID- 14677446
TI  - The neurosurgeon as an intensivist.

PMID- 14677447
TI  - Certification of neurosurgeons: a transition from neurosurgical certification and
      recertification to maintenance of certification. Report from the American Board
      of Neurological Surgeons.

PMID- 14677448
TI  - Acoustic tumors: operation versus radiation--making sense of opposing viewpoints.
      Part I. Acoustic neuroma: decision making with all the tools.

PMID- 14677449
TI  - Acoustic tumors: operation versus radiation--making sense of opposing viewpoints.
      Part II. Acoustic neuromas: sorting out management options.
AB  - Patients with acoustic neuromas have several options available to them. Large
      tumors with significant brain stem compression usually require surgical
      resection. For patients with small or medium-sized tumors, radiosurgery has
      become a common treatment, with excellent long-term results being reported.
      Patients must be comfortable with the concept of tumor control rather than tumor
      removal. Most seem to be satisfied with this concept if it allows them to avoid
      brain surgery. Surgeons should strive to educate their patients with information
      from the peer-reviewed literature. Confusion exists among patients, because the
      information from Internet sources, newsletters, support groups, and physicians
      has not always been validated and supported by outcomes data. Although we are
      asked to provide our opinions, our comments should not be based on myth,
      conjecture, training bias, or socioeconomic concerns.

PMID- 14677450
TI  - Honored guest presentation: the neurosurgeon as mentor and student.

PMID- 14677451
TI  - CNS Resident Award: role of the lateral premotor cortex in articulation.

PMID- 14677453
TI  - Synthes Award for Resident Research in Brain and Craniofacial Injury: poloxamer
      188 volumetrically decreases neuron loss in the rat model of excitotoxicity in a
      time-dependent manner.

PMID- 14677452
TI  - Tumor Young Investigator Award: induction of glioblastoma multiforme in primates
      after fractionated whole-brain irradiation in the therapeutic dose range.

PMID- 14677454
TI  - Ronald Tasker Award: a novel model of neuroma pain.

PMID- 14677455
TI  - CSNS Resident Award: the economics of trigeminal neuralgia surgery.

PMID- 14677456
TI  - CSNS Young Neurosurgeon Award: is it appropriate to treat complex cerebrovascular
      pathology in nonacademic medical centers?

PMID- 14677457
TI  - [Problems with clinical use of recombinant proteins].

PMID- 14677458
TI  - [Professionalism is essential in family practice].

PMID- 14677459
TI  - [Immunogenicity of biopharmaceuticals. Experiences with beta-interferon, EPO and
      anti-TNF].

PMID- 14677460
TI  - [Artificial fertilization and HIV-positive couples--a risk-reducing treatment].

PMID- 14677461
TI  - [Nepotism in peer review of applications for research grants].

PMID- 14677462
TI  - [Comment to the article "Nepotism in peer review of applications for research
      grants"].

PMID- 14677463
TI  - [Can admission of acutely ill internal medicine patients to an intermediate care
      unit replace hospital admission?].

PMID- 14677464
TI  - [Experiences with infliximab in the treatment of active rheumatoid arthritis and
      spondyloarthropathy].

PMID- 14677465
TI  - [Anti-TNF-alpha-treatment of arthritis--4-year follow-up].

PMID- 14677466
TI  - [How do general practitioners prioritize various aspects of medical care?].

PMID- 14677467
TI  - [Ascites puncture].

PMID- 14677468
TI  - [Picture of the month: lupus erythematosus].

PMID- 14677469
TI  - [HOPE exchange 2002].

PMID- 14677470
TI  - [Rehabilitation of patients treated with implantable defibrillator].

PMID- 14677471
TI  - [The medical society and asylum seekers].

PMID- 14677472
TI  - [Evidence-based hospital planning--or what?].

PMID- 14677473
TI  - [The reversed gatekeeper].

PMID- 14677474
TI  - [Confusing drug information].

PMID- 14677475
TI  - [Two women with a chronic process in the lower abdomen].
AB  - Two women, aged 50 and 45 years, had a chronic process in the lower abdomen. The
      first presented with cough and progressive dyspnoea, and her chest X-ray raised
      the suspicion of a metastasis of a malignancy. The second patient had abdominal
      pain, frequent urination and irregular vaginal bleeding. She was initially
      treated for a urinary-tract infection. Diagnostic investigations showed pelvic
      actinomycosis in both patients. Both had used an intrauterine device (IUD). In
      the first patient a pelvic abscess was drained. Antimicrobial treatment consisted
      of penicillin i.v. for several weeks and orally for 6 months. Actinomycosis is a
      slowly progressive bacterial infection that characteristically expands through
      anatomic structures and can lead to fistulae and abscesses. The disease is caused
      by Actinomyces species. Diagnosis is often delayed because other diseases (e.g.
      malignancy) are considered more probable. Actinomycosis is associated with
      prolonged use of an IUD, but it is rare and removal of the IUD is not indicated
      unless symptoms of pelvic inflammatory disease are present. The mainstay of
      actinomycosis therapy is administration of an effective antibiotic (e.g.
      penicillin). Except for drainage of abscesses, surgical intervention is rarely
      necessary. When antimicrobial therapy is continued for 6-9 months, prognosis is
      favourable, as was the case in both patients.

PMID- 14677476
TI  - [Calprotectin: a fecal marker for diagnosis and follow-up in patients with
      chronic inflammatory bowel disease].
AB  - Chronic inflammatory bowel disease (IBD) is characterised clinically by periods
      of well being interspersed by exacerbations of disease activity. Differentiation
      between IBD and less severe disorders such as irritable bowel syndrome requires
      invasive and expensive diagnostic procedures. Diagnostic differentiation between
      active disease, symptoms due to residual constriction of the fibrotic lumen and
      functional symptoms is a well-known problem. There are not yet any laboratory
      parameters with sufficient discrimination in terms of sensitivity and
      specificity. Colonoscopy and histopathological examination remain the gold
      standards: in Crohn's disease this may be complex due to the variable
      localisation of the inflammatory process. Abdominal scintigraphic procedures,
      although informative, are complex and expensive. The recent assessment of faecal
      calprotectin, a calcium- and zinc-binding anti-inflammatory protein found in
      neutrophilic granulocytes and monocytes, offers an attractive alternative as an
      index of intestinal inflammation. We measured this stable marker in random stool
      samples from 187 patients including healthy volunteers, patients with
      endoscopically classified active IBD or IBD in remission, and patients with other
      gastrointestinal disorders. Disease activity was monitored by clinical symptoms,
      blood tests and endoscopy. Our results confirm previous literature findings that
      faecal calprotectin is a promising and useful non-invasive tool in the screening
      of patients presenting with abdominal pain and diarrhoea. Moreover, calprotectin
      seems helpful in differentiating between active and non-active IBD and possibly
      also in the monitoring of disease activity.

PMID- 14677477
TI  - [Nutrition and health--toxic substances in food].
AB  - With respect to food, the most important factors causing adverse health effects
      are: an unbalanced diet, resulting in obesity or vitamin deficiencies,
      overconsumption of alcohol or fat, the presence of microbial contamination and
      the presence of natural toxins. Two additional factors, the presence of
      environmental contaminants and products formed on heating food, may also be of
      importance. It is generally assumed that, when combined, food-related factors
      contribute to around 35% of overall cancer incidence. The most important groups
      of health-threatening compounds to be found in the food chain include natural
      toxins, such as those produced by plants (phytotoxins), fungi (mycotoxins),
      marine algae (phycotoxins) and by bacteria, and toxins present in animals for
      human consumption, especially fish. A second important group of toxic compounds
      in food consists of environmental contaminants, including heavy metals and
      persistent organic pollutants, such as dioxins and polychlorinated biphenyls, all
      of which may unintentionally end up in the food chain. A third group of toxins
      present in food are those substances produced when food is heated, and include
      polycyclic aromatic hydrocarbons, heterocyclic amines and acrylamide.

PMID- 14677478
TI  - [Percutaneous dilatating tracheostomy in intensive-care patients: technique,
      indications and complications].
AB  - Since tracheal cannulas are increasingly used to wean intensive-care patients
      from respiratory machines, more doctors and nurses will find themselves having to
      take care of patients with tracheostomas. Indications for tracheal cannula use
      include the likelihood of prolonged mechanical ventilation and/or difficult
      weaning. Percutaneous dilatational tracheotomy is a relatively simple procedure
      for inserting a tracheal cannula. It is performed using a modified Seldinger
      technique, carried out under general anaesthesia; use of a bronchoscope during
      the operation makes the procedure simpler and safer. When it is difficult to
      pinpoint the source of problems arising in patients fitted with a tracheal
      cannula, it must always be considered that the cannula might be the cause.
      Although rare, complications may arise several weeks or months after
      decanulation, such as stenosis of the trachea, changes in voice and fistula
      formation between the trachea and skin. A strict surveillance protocol is needed
      to recognize and treat late complication.

PMID- 14677479
TI  - [Diagnostic image (167). A coughing woman with abnormalities on her chest
      radiogram. Aspergilloma in a necrotic lung carcinoma].
AB  - A 40-year-old woman presented with cough and fever. Chest radiography showed a
      cavity, due to an aspergilloma growing in a necrotic lung carcinoma.

PMID- 14677480
TI  - [Hospital-wide vascular screening program at the University Medical Center,
      Utrecht: prevalence of risk factors and asymptomatic vascular disease from 1996
      to 2002].
AB  - OBJECTIVE: Tracing and treating cardiovascular risk factors in patients with
      arterial vascular disease and in patients with high risk of developing vascular
      diseases. DESIGN: Descriptive. METHOD: In September 1996 at the University
      Medical Center Utrecht, the Netherlands, a vascular screening and prevention
      programme was started for newly referred patients aged between 18 and 79 years
      presenting with one or more of the following: coronary artery disease,
      cerebrovascular disease, peripheral arterial disease, hypertension, diabetes
      mellitus or lipid disorders. In all patients, risk factors for developing (new)
      vascular diseases were assessed and non-invasive vascular diagnostics aimed at
      finding asymptomatic vascular disease were done. RESULTS: Between 1 September
      1996 and 31 October 2002, 3075 patients took part in the screening programme.
      Within the various patient groups and often despite treatment, there was a high
      prevalence of hypertension, smoking, dyslipidaemia, hyperhomocystemia and
      overweight. In patients with peripheral artery disease, carotid artery stenosis >
      or = 50% was detected in 17% and an aneurysm of the abdominal aorta in 5%. In
      patients presenting with diabetes mellitus, hypertension or lipid disorders the
      prevalence of asymptomatic arterial disease was 1-5%. Asymptomatic vaso-dilatory
      disease in particular was uncommon. CONCLUSION: A hospital-wide vascular
      screening and prevention programme for a wide range of high-risk vascular
      patients was shown to be feasible and resulted in the detection of risk factors
      and asymptomatic arterial disease. It is a reliable starting point for actual
      risk intervention. More attention should be paid to treating existing risk
      factors.

PMID- 14677481
TI  - [Unavoidable surgical intervention in two women with severe actinomycosis during
      IUD use].
AB  - Extensive abdominal infections with Actinomyces were diagnosed in two women aged
      35 and 33 years respectively, who suffered from the nonspecific symptoms fever
      and abdominal pain. These infections occur more often in women with an
      intrauterine device. Development of an abdominal mass with ureter or bowel
      obstruction may cause hydronephrosis and mechanical ileus. The patients underwent
      a laparotomy and a double-J catheter was inserted, which could be removed later
      on (temporary stoma). Treatment included high-dose penicillin i.v. followed by
      oral amoxicillin. Both patients recovered. It may be difficult to establish this
      diagnosis: the first patient was diagnosed by histopathological examination, in
      the second Actinomyces had been found in a routine cervical smear a few years
      earlier.

PMID- 14677482
TI  - [Intracranial actinomycosis in a child with dental caries].
AB  - A diagnosis of intracranial actinomycosis was made in a 9-year-old boy with
      headache, cranial nerve dysfunction and ataxia. Poor dental hygiene leading to
      caries and an inflammation in his right upper jaw probably was the cause of
      cervicofacial actinomycosis with intracranial extension. A full recovery was
      achieved by treatment with benzylpenicillin. Actinomyces is a gram-positive
      bacterium belonging to the endogenous flora of the mucous membranes of the
      oropharynx, gastrointestinal tract, and female genital tract. Disruption of the
      mucous membrane is the portal of entry for an extremely destructive infective
      process that is effectively treated with penicillin. Good orodental hygiene is
      important for the prevention of actinomycosis.

PMID- 14677483
TI  - [Unused knowledge? A useful result of research from the funded Investigative
      Medicine program].
AB  - Many policy-makers believe that the translation of research findings into daily
      practice is poor. Examples of projects from the research programme 'Investigative
      medicine' over the period 1990-1995 show that this opinion is not correct.
      Findings from medical technology assessments that focus on clinical decision
      making were usually translated into clinical practice very quickly, sometimes
      even before clinical guidelines had been produced or revised. In almost all
      cases, the formulation of governance policies concerning the financing and
      distribution of medical services and interventions required considerably more
      time.

PMID- 14677484
TI  - [Acute dysphasia: often there is a readily treatable cause].

PMID- 14677485
TI  - [Acute dysphagia: often there is a readily treatable cause].

PMID- 14677486
TI  - [Tumor growth during the waiting period for radiotherapy in patients with
      oropharyngeal carcinoma].

PMID- 14677487
TI  - [Challenges and risks in the development of the ego ideal in adolescence].
AB  - The author proposes to speak of representations concerning the ideal self, the
      ideal relationship, the ideal society instead of ego ideal. An active self
      develops ideals and uses them as standards for orientation, to regulate the
      affects, and to fulfill needs. The different ideals often do not fit together and
      are therefore difficult to realize. Adolescents normally refuse their parents'
      ideals and create new ones with the help of their peers. This developmental step
      is full of challenges and risks as will be explained in this article.

PMID- 14677488
TI  - [Systematic application of visualized solution algorithms and verbal self
      instruction in spelling remediation: initial results of general practice
      outcomes].
AB  - In this study the effects of a remedial spelling training approach were
      evaluated, which systematically combines certain visualization and verbalization
      methods to foster students' spelling knowledge and strategy use. Achievement
      related pre- and posttest data of two treatment cohorts including children and
      adolescents with severe spelling disabilities were analyzed. The treatment was
      administered in single-case or small group sessions and took about 85 hours in
      average. In each cohort empirical results could demonstrate statistically
      significant increases in students' spelling test performance.

PMID- 14677489
TI  - [Outcomes of prevention and treatment of adolescent psychiatric disorders in
      Turkish immigrants with reference to resources and risks].
AB  - Semi-structured bilingual interviews were conducted with 223 adolescents from
      Turkey and their parents in 77 volunteering immigrant families (field group) and
      in 40 outpatient families attending the adolescent service (CAP treatment group).
      Risks and resources for mental health were assessed in a qualitative approach
      based on contextual family theory, cohesion and adaptability according to Olson's
      Clinical Rating Scale. While adolescent psychiatric morbidity in the field group
      equalled an expected rate of 24%, families with psychologically healthy offspring
      significantly excelled in parental and child resources. Yet, resources did not
      separate symptomatic and non-symptomatic families (referring to child symptoms)
      as well as risks did. A parent without work constituted a risk factor of its own.
      Differentiating CRS from 3 to 4 steps of adequacy for child health (introducing a
      range of high cohesion or high rigidity alone as another step between normal and
      dysfunctional) led to classify 80% of non-symptomatic families as functional.
      Following our results, a resource oriented family therapy seems to be the most
      promising therapeutic approach. Social case management should be provided for at
      the same time.

PMID- 14677490
TI  - [Assessment of "self and other perception" of parents in family court disputes
      based on the Giessen Test].
AB  - 30 couples were assessed using the Giessen-Test in regard to their self-images
      and how they were perceived by their partners. All couples were examined in the
      course of domestic proceedings at the Department of Psychiatry and Psychotherapy
      in Childhood and Adolescence (University of Tubingen). Differences between self
      image and the partners perception as well as self-image and rating of the partner
      were worked out. The degree of symmetry and correspondence regarding gender
      positions and the degree of confirmation/negation of the position were pointed
      out. No sex differences could be found in regard to role attribution. Sings of
      sex-specific role perception could not be shown amongst the couples being part of
      the domestic proceedings. Sex-specific differences in regard to the image as
      perceived by the other parent do not exist any more. The exact complementary role
      of ones own role-perception is being attributed to the former partner. The role
      characteristics attributed to the former partner can be described as dominant,
      under-controlled, hypomanic, and inaccessible. Family- and psychodynamic aspects
      of these results are discussed.

PMID- 14677491
TI  - [Admission with freedom restriction of minors to child and adolescent
      psychiatrics clinics--medical decisions without regard for psychodynamic
      sequelae?].
AB  - The placement of minors who have been given a custodial sentence is barely
      mentioned in child psychiatric literature. The aim of this contribution is to
      present the statutory rules in civil law and public law regulating placement and
      to discuss the similarities and differences between them. The legislation on the
      placement of minors, which is concurrent in most of the German states, and the
      resulting problems for legal laypersons (such as doctors) are explained.
      Uncertainties among family and guardianship courts in regard to application of
      the law are examined. Case reports are presented to show the relevance to
      clinical practice. The conclusion can be drawn that the competing legislative
      regimes must be taken into account in each individual case when placing minors
      who have been given a custodial sentence. The application of legislation should
      take into account psychodynamic effects on the minor and his or her parents or
      guardians. Under certain circumstances, an insufficiently considered legal
      decision can have a counterproductive effect on the course of the disease. It is
      therefore recommended to proceed according to the principle of "priority to the
      better form of placement" when placing minors who have been given a custodial
      sentence.

PMID- 14677493
TI  - Breast cancer management in the new millennium--a multidisciplinary approach.

PMID- 14677492
TI  - Voluntary HIV testing and counselling at the workplace--entirely compatible with
      the Employment Equity Act.

PMID- 14677494
TI  - Ritalin--on the bandwagon?

PMID- 14677496
TI  - Drug pricing: the end of the gravy train?

PMID- 14677495
TI  - Sunter throws his cap into SAMA's ring.

PMID- 14677497
TI  - Doctors, ethicists hit out at third-party funders.

PMID- 14677498
TI  - A doctor with a modern AIDS mission.

PMID- 14677499
TI  - First sudden infant death awareness campaign launched in South Africa.

PMID- 14677500
TI  - Medical aid options for ageing patients.

PMID- 14677501
TI  - The alcohol injury fund.

PMID- 14677502
TI  - The partogram.

PMID- 14677503
TI  - Public health and vaccines--immune responses in developed versus poor countries.

PMID- 14677504
TI  - Stroke in the young.

PMID- 14677505
TI  - Eprex (recombinant human erythropoietin alfa) and pure red cell aplasia-
      recommendations for administration to patients with CRF.

PMID- 14677506
TI  - Commerce in organs--an ethical dilemma.

PMID- 14677507
TI  - Management of diabetes mellitus in outpatient facilities is achieving poor
      results.

PMID- 14677508
TI  - Cancer in rural KwaZulu-Natal.

PMID- 14677509
TI  - Evidence-based benefits. HIV screening in the management of HIV/AIDS.

PMID- 14677510
TI  - Death and injury on duty--a study of South African police officers.
AB  - OBJECTIVES: Sections of contemporary South African society are characterised by
      high levels of crime and interpersonal conflict. The South African Police Service
      (SAPS) is in the front line, with many deaths and injuries occuring among serving
      officers in recent years. The circumstances and nature of the injuries sustained
      by these officers have received little attention in the medical literature.
      DESIGN: A retrospective review of all injured SAPS members was undertaken at a
      single level one trauma centre in Johannesburg between June 1993 and June 2002.
      The following factors were recorded: demographics, mechanism and anatomical site
      of injury, mode of transportation to hospital, whether personal protection had
      been used, mortality, and return to work. RESULTS: One hundred and thirty-four
      SAPS personnel were admitted over a 9-year period. The majority (95%) were male
      and the median age was 31 years. One hundred and thirty-two were on duty and two
      were in transit to a place of duty when injured. Ninety-two (69%) were injured by
      gunshot, (including 3 attempted suicides and 9 injuries due to negligent
      discharge), 2 members were stabbed, 31 were involved in motor vehicle accidents,
      2 in motorbike accidents, 1 member was struck by a car while directing traffic, 3
      officers were injured by falls from a height, 2 members were injured in
      helicopter crashes, and 1 member required treatment for gas inhalation.
      Documentation on whether some form of personal protection was worn at the time of
      injury was only available for 43 of the 92 cases of gunshot wounds (47%); of
      these, only 15 (35%) were wearing a bulletproof vest. Use or non-use of a seat
      belt was documented by hospital staff for only 6 of the 31 officers (19%) injured
      in motor vehicle accidents. None of the 6 officers had been restrained by a
      seatbelt. Nineteen SAPS personnel (14%) died of their injuries, but the majority
      of surviving members returned to duty. CONCLUSION: There is an unacceptably high
      level of violence in South African society today and SAPS members regularly have
      to deal with dangerous or violent situations. There is a clear need to introduce
      a reporting system within the SAPS to record the use of personal protection by
      officers. Education needs to target SAPS members in order to enhance their use of
      personal protection. There is a further need to design and implement personal
      protection that will be universally acceptable by SAPS members.

PMID- 14677511
TI  - Dual protection in sexually active women.
AB  - OBJECTIVE: To determine the prevalence and co-factors associated with the
      practice of dual protection against sexually transmitted infections (STIs) and
      unwanted pregnancy in a cross-sectional sample of South African women. DESIGN:
      Secondary analysis of cross-sectional household survey data. METHODS: Statistical
      analysis of responses by sexually active women to the question, 'Was a condom
      used on the last occasion you had sex?' were obtained from the women's
      questionnaire of the South African Demographic and Health Survey in relation to a
      number of other variables. RESULTS: (i) 10.5% of all sexually active women aged
      15-49 years used a condom at last sex and 6.3% used a condom as well as another
      contraceptive method; (ii) condom use is more likely among younger, more
      educated, more affluent, and urban women, and among women who change partners
      more frequently; (iii) reasons for not using condoms are more likely to be
      associated with the personal attitudes of women or their partners than with poor
      knowledge of or lack of access to condoms; (iv) women who have no need or desire
      to prevent pregnancy are less likely to use condoms; and (v) there is a minority
      of sexually active women, characterised by social disadvantage, who have
      difficulty obtaining condoms. CONCLUSIONS: There is an urgent need for targeted
      programmes that increase dual protection with condoms.

PMID- 14677512
TI  - 'Failed' contraception in a rural South African population.
AB  - OBJECTIVE: To investigate whether the free availability of contraception affects
      the need for termination of pregnancy (TOP). DESIGN: Case-control study. SETTING:
      South African rural hospital. POPULATION: Three thousand and ninety-five TOP
      seekers and 439 non-pregnant controls. METHODS: Structured questionnaire followed
      by ultrasonography. MAIN OUTCOME MEASURES: Current use or recent discontinuation
      of contraception and the reason for discontinuation. RESULTS: Less than one-third
      (28.6%) of TOP seekers claimed to be using contraception versus 85.0% of
      controls. Injectable contraception (IC) was preferred by the controls and oral
      contraception (OC) by TOP seekers (chi 2 = 48.5, p < 0.0001, OR 0.34 (95%
      confidence interval 0.25, 0.46)). The percentage of discontinuation of hormonal
      contraception was higher in controls (chi 2 = 6.3, p = 0.012, OR 0.51 (0.31,
      0.85)). The reason for discontinuation of hormonal contraception was obtained
      from 31.2% of TOP seekers and 63.3% of controls; no reason for discontinuation
      was acknowledged by 30.1% of the former and 6.3% of the latter (chi 2 = 33.4, p <
      0.0001, OR 6.40 (3.25, 12.56)). Side-effects of hormonal contraception prompted
      more discontinuation in the failed-contraception group (chi 2 = 120.5, p <
      0.0001, OR 49.4 (21.6, 112.5)). Poor compliance and absence of an acknowledged
      reason for discontinuing hormonal contraception resulted in 173 unwanted
      pregnancies. CONCLUSION: In South Africa two main components of women's
      reproductive health and rights are freely available, namely contraception and
      TOP. Not using contraception is one of the main causes of unwanted pregnancy.
      Better education of both service providers and users is needed to improve use,
      compliance and perseverance with contraception.

PMID- 14677513
TI  - Informed choice--the timing of postpartum contraceptive initiation.
AB  - BACKGROUND: In South Africa injectable progestogen-only contraceptives (IPC) are
      typically administered to women immediately after delivery. Several guidelines
      advise that breast-feeding women should not commence IPC until 6 weeks postpartum
      on the basis of theoretical risks to the infant. OBJECTIVE: We examined women's
      preferences regarding timing of postpartum IPC initiation, as well as women's
      contraceptive and breast-feeding behaviours and pregnancy risk in the early
      postpartum period. DESIGN AND DATA COLLECTION: A cross-sectional study was
      conducted among 200 antenatal clinic (ANC) attendees and 180 mothers attending a
      child health clinic (CHC). At the ANC, women were given information on the
      theoretical risks of IPC and re-interviewed about their postpartum contraceptive
      intentions. RESULTS: Most ANC women planned to use IPCs (92%) and to breast-feed
      (98%) after delivery. Most CHC mothers had used IPCs (91%) and had breast-fed
      (83%) after delivery. When women at the ANC were provided with appropriate
      information they made decisions about when to initiate IPC by balancing the
      theoretical risks of IPC to their infant against their personal risk of pregnancy
      and ability to return to a clinic in the early postpartum period. CONCLUSION: It
      is important to include informed choice in postpartum IPC initiation guidelines.

PMID- 14677514
TI  - Visuospatial deficits in children 3-7 years old with shunted hydrocephalus.
AB  - OBJECTIVE: To define non-verbal intelligence deficits in children 3-7 years of
      age following shunted hydrocephalus (HCP). DESIGN: Prospective randomised single
      blinded study. Thirty shunted HCP (study) and 30 cardiac (control) patients
      between the ages of 3 and 7 years were compared on eight non-verbal subtests of
      the Junior South African Individual Scales (JSAIS). SETTING: Department of
      Neurosurgery at Wentworth Hospital, Durban, South Africa. RESULTS: Significant
      differences between the HCP and cardiac groups were recorded on all eight
      subtests of the JSAIS. The HCP group experienced problems with spatial
      orientation, perceptual planning and organisation, emotive deficits, abstract
      thinking and visual concepts. CONCLUSION: All patients with shunted HCP had
      specific deficiencies in defined cognitive areas of non-verbal intelligence when
      compared with the controls. Further studies are warranted to determine the
      effects of ventriculoperitoneal shunting on non-verbal intelligence so that the
      special educational needs of HCP children may be met.

PMID- 14677515
TI  - Production of pilot lots of inactivated influenza vaccine in response to a
      pandemic threat: an interim biosafety risk assessment.

PMID- 14677516
TI  - [Image of the month. Pulsus alternans, an old sign reviewed by Doppler
      echocardiography].

PMID- 14677518
TI  - [How I treat ... hypertrichosis].
AB  - Hypertrichosis can result from various origins and exhibit diverse clinical
      presentations. Any etiological treatment, when available, does not always lead to
      regression of the excess in pilosity. Most often, hypertrichosis represents a
      real esthetic burden and affects the patient's self-esteem. Currently the laser
      epilation technique offers new and promising therapeutic possibilities.

PMID- 14677517
TI  - [Image of the month. Myocardial bridging...].
AB  - Myocardial bridging, often congenital, is an aberrant relationship between
      epicardial coronary segments and the myocard, usually affecting the
      interventricular artery. Although often asymptomatic, this coronarographic
      detection (milking effect by systolic compression) has been associated with
      ischaemia, rhythm disturbances or sudden death. Different treatments may be
      considered, from pharmacological intervention to surgery, and above all,
      percutaneous angioplasty with stenting. A clinical case leads us to a review of
      the literature.

PMID- 14677519
TI  - [Clinical case of the month. Precordialgia evoking a coronary instability
      syndrome, a diagnostic danger].
AB  - Chest pain represents a frequent motivation for consultation in which the
      differential diagnosis is not always easy. We present a case where a misdiagnosis
      lead to serious complications. Therefore we review the clinical and
      electrocardiographic characteristics of the evoked diagnosis.

PMID- 14677520
TI  - [Rapid analysis of circulating cardiac natriuretic peptides. A new contribution
      to the diagnosis, regular treatment and prognosis of cardiovascular diseases].
AB  - Only about half of the diagnoses of heart failure are correct. The limitations of
      clinical judgment and complementary investigations are described in this article.
      Recently, BNP was found to be a good biological marker of ventricular
      dysfunction. Rapid and reliable BNP measurement is now available and the clinical
      value of this peptide was examined in many studies. The role of BNP in the
      diagnosis and management of heart failure will be increasing.

PMID- 14677521
TI  - [Statins for the brain?].
AB  - Whether cholesterol lowering decreases risk of stroke has long remained unclear.
      Large epidemiological studies have found only weak links between cholesterol
      levels and stroke. Recent studies with statins, more potent cholesterol lowering
      agents, have now demonstrated significant reductions of stroke incidence and
      total mortality when administered for secondary prevention in patients with wide
      ranges of cholesterol values. It remains unknown if a statin is superior to
      others for the secondary prevention of stroke.

PMID- 14677522
TI  - [Sneddon and Wilkinson's subcorneal pustulosis].
AB  - The subcorneal pustular dermatosis of Sneddon and Wilkinson belongs to the
      heterogeneous group of neutrophilic dermatosis. This unique disorder is
      characterized by a superficial pustular eruption. The pustules are flaccid and
      aseptic. They develop predominantly on the trunk and in the groins, axillae and
      submammary areas. This disease is benign and chronic. However, it can be
      associated with some other conditions such as lymphoproliferative and
      myeloproliferative diseases. Dapsone is the treatment of choice to control the
      skin manifestations.

PMID- 14677523
TI  - [Early hormonal exposure and behavior effects in congenital adrenal hyperplasia:
      a case report].
AB  - Congenital adrenal hyperplasia is a recessive autosomal transmission endocrine
      pathology that exposes people who suffer from it to an abnormally high
      concentration of adrenal androgens during the prenatal and early postnatal
      periods. This disease induces female's virilism of variable degree. The case of a
      29 year-old patient, who suffers from this affection and also presents a
      psychiatric disorder, raises questions about the possible consequences of an
      early exposure to androgens on the adult behaviour.

PMID- 14677524
TI  - [Hand, foot and mouth disease, a not so benign affection: clinical reminder and
      potential complications].
AB  - Hand-foot-and-mouth disease is an infection appearing in epidemics and due, in
      most cases, to Coxsackie-virus A16 and/or Enterovirus 71 or, less often, to other
      Coxsackie-virus serotypes. The symptomatology mostly consists in vesicular
      eruption of the anterior part of the buccal mucosa as well as of hands and feet.
      Its evolution, although often benign, can include cardiopulmonary and
      neurological complications. The latter complications require a quickly detection
      and treatment, and prevention of virus transmission to other people must be
      adequate.

PMID- 14677525
TI  - [How I explore ... a Morton's neuroma].
AB  - Morton's neuroma is a frequent cause of pain in the forefoot that commonly occurs
      in the third intermetatarsal space. It is a type of nerve compression syndrome
      which involves the common digital plantar nerves. The diagnosis is typically made
      on the basis of history and careful physical exam. Imaging procedures may be
      useful to diagnose an atypical case or postoperative recurrence. Conservative
      treatments are successful in most cases, but when they fail surgery may be
      considered.

PMID- 14677526
TI  - [Medication of the month. Gliclazide modified release (Uni Diamicron)].
AB  - Gliclazide modified release that has been recently launched by Servier (Uni
      Diamicron 30 mg) is a new formulation of gliclazide to be given once daily. The
      original hydrophilic matrix improves the biodisponsibility of gliclazide and
      allows a progressive release of the drug that better parallels the 24-hour
      glycaemic profile of patients with type 2 diabetes mellitus. Such characteristics
      may explain the rather low risk of hypoglycaemic episodes and the morning
      administration should contribute to improve patient's compliance. As the common
      formulation of gliclazide, the modified release formulation is indicated in the
      treatment of type 2 diabetes, in adult subjects, when diet, exercise and weight
      loss are insufficient to restore an adequate metabolic control. It may be used
      alone or in combination with metformin, glitazones, acarbose or insulin, with the
      same general principles of use as for the classical formulation of gliclazide.

PMID- 14677527
TI  - [Clinical study of the month. The CHARM study].
AB  - In parallel, randomized, double-blind, controlled clinical trials, candesartan
      (titrated to 32 mg once daily) was compared to placebo in 3 distinct populations:
      1) patients with symptomatic heart failure (SHF) and left ventricular ejection
      fraction (LVEF) 40% or less who were not receiving an ACE inhibitor because of
      previous intolerance (CHARM-Alternative); 2) patients with SHF and LVEF 40% or
      less who were currently receiving an ACE inhibitor (CHARM-Added); 3) patients
      with SHF and LVEF higher than 40% (CHARM-Preserved). The primary outcome for the
      overall programme (CHARM-Overall) was all-cause mortality. For the component
      trials, it was a composite of cardiovascular death and hospital admission for
      CHF. Analysis was by intention to treat. In CHARM-Overall (placebo, n = 3796;
      candesartan, n = 3803; mean follow-up; 37.7 months), candesartan induced a 1.6%
      absolute reduction in all-cause mortality (unadjusted HR: 0.91; 95% CI 0.83-1.00;
      p = 0.055). In a prespecified analysis with covariate adjustment, this was
      statistically significant (HR: 0.90; 95% CI 0.82-0.94; p = 0;032). A highly
      significant reduction in the combined incidence of cardiovascular death and CHF
      hospital admission (HR: 0.84; 95% CI 0.77-0.91; p < 0.0001) was noted as well as
      a reduction of the number of patients developping a new diabetes (6% vs 7.4%: p =
      0.02). In CHARM-Alternative, there were 1013 patients on candesartan and 1015 on
      placebo and the mean follow-up was 33.7 months. The combined incidence of
      cardiovascular death and CHF hospitalization was reduced by 23% (p = 0.0004). In
      CHARM-Added, 1276 patients received candesartan and 1272, placebo; mean follow-up
      was 41 months. The benefit induced by candesartan on the primary endpoint was 15%
      (p = 0.011). In those two studies the two components of the primary endpoint were
      significantly reduced. Candesartan was beneficial in all prespecified subgroups,
      including patients concomitantly treated by beta-blockers. In CHARM-Preserved
      (candesartan, n = 1514; placebo, n = 1509; mean follow-up: 36.6 months), neither
      the composite endpoint, nor cardiovascular death were reduced, but the number of
      admissions for heart failure was reduced. The clinical implications of these
      important results are discussed.

PMID- 14677528
TI  - Stretching water--Queensland's water use efficiency cotton and grains adoption
      program.
AB  - The Cotton and Grains Adoption Program of the Queensland Rural Water Use
      Efficiency Initiative is targeting five major irrigation regions in the state
      with the objective to develop better irrigation water use efficiency (WUE)
      through the adoption of best management practices in irrigation. The major
      beneficiaries of the program will be industries, irrigators and local
      communities. The benefits will flow via two avenues: increased production and
      profit resulting from improved WUE and improved environmental health as a
      consequence of greatly reduced runoff of irrigation tailwater into rivers and
      streams. This in turn will reduce the risk of nutrient and pesticide
      contamination of waterways. As a side effect, the work is likely to contribute to
      an improved public image of the cotton and grain industries. In each of the five
      regions, WUE officers have established grower groups to assist in providing local
      input into the specific objectives of extension and demonstration activities. The
      groups also assist in developing growers' perceptions of ownership of the work.
      Activities are based around four on-farm demonstration sites in each region where
      irrigation management techniques and hardware are showcased. A key theme of the
      program is monitoring water use. This is applied both to on-farm storage and
      distribution as well as to application methods and in-field management. This
      paper describes the project, its activities and successes.

PMID- 14677529
TI  - Sub-Tenon's administration of local anaesthetic: a review of the technique.

PMID- 14677530
TI  - Sub-Tenon's administration of local anaesthetic: a review of the technique.

PMID- 14677531
TI  - Use of PCA morphine as the sole analgesic for postoperative pain relief after
      TAH.

PMID- 14677532
TI  - The challenge of assessing and managing pain in early and later life.

PMID- 14677533
TI  - Clinical alert: failure in face of mask seal as a consequence of incorrect face
      mask assembly.

PMID- 14677535
TI  - Another death after percutaneous dilational tracheostomy.

PMID- 14677537
TI  - Leukocyte Trafficking: The Role of Fucosyltransferases and Selectins. Proceedings
      of the 44th ESRF Workshop. Berlin, Germany, 30 October-1 November 2002.

PMID- 14677536
TI  - Smallpox Vaccine Injury Compensation Program: administrative implementation.
      Interim final rule.
AB  - The Smallpox Emergency Personnel Protection Act of 2003 (SEPPA), authorizes the
      Secretary of Health and Human Services (the Secretary), to establish the Smallpox
      Vaccine Injury Compensation Program ("the Program"). This program is designed to
      provide benefits and/or compensation to certain persons harmed as a direct result
      of receiving smallpox covered countermeasures, including the smallpox vaccine, or
      as a direct result of contracting vaccinia through certain accidental exposures.
      In addition, the Secretary may provide death benefits to certain survivors of
      individuals who died as the direct result of these injuries. On August 27, 2003,
      the Secretary published an interim final rule that set out a Smallpox (Vaccinia)
      Vaccine Injury Table ("the Table"). The table includes adverse effects (including
      injuries, disabilities, conditions, and deaths) within specific time periods that
      shall be presumed to result from the receipt of, or exposure to, the smallpox
      vaccine. The Secretary will use this table, as well as the procedures set out in
      this regulation, in deciding whether persons are eligible to receive benefits
      under the program. In this interim final rule, the Secretary is setting out the
      administrative policies, procedures, and requirements governing the program, as
      authorized by the SEPPA. The Secretary is seeking public comment on this interim
      final rule.

PMID- 14677538
TI  - Special issue on Herman J. Phaff: Learning from yeasts.

PMID- 14677539
TI  - Intent-to-treat analysis.

PMID- 14677540
TI  - Evolution of erythrocyte aggregation in transmural myocardial infarction
      survivors. A 12-month follow-up study.

PMID- 14677541
TI  - 6TG: when less is more than you bargained for.

PMID- 14677542
TI  - The light at the end of the tunnel.

PMID- 14677543
TI  - Hold the bone: good news for young women with IBD.

PMID- 14677544
TI  - An oil that keeps you slim?

PMID- 14677545
TI  - Cut the fat.

PMID- 14677546
TI  - Ephedra: heart dangers in disguise.

PMID- 14677547
TI  - Body-fat scales: will they help?

PMID- 14677548
TI  - FDA requires warnings on anti-malaria drug Lariam.

PMID- 14677549
TI  - Did you know? Prussian blue dye.

PMID- 14677550
TI  - HIV tests: fast results vs. privacy protection.

PMID- 14677551
TI  - Origin of life. II. From prebiotic replicators to protocells.
AB  - Primitive microvesicles (coacervates, microspheres, marigranules, etc.), free
      born in aqueous media, are only protometabolic proteinoids surrounded by an
      amphiphilic protomembrane. In contrast, surface-born microvesicles could be
      initiated in the pores of watered rocks providing primary boundaries coated by
      amphiphilic compounds and acting as sinks for primitive peptides and their coding
      nucleobases N-P anchored on polyphosphates. Only presumed replication of these
      prenucleic infopolymers would qualify the basipetally budded microvesicles as
      protocells.

PMID- 14677552
TI  - Diving into the depths of immersive 3D.

PMID- 14677553
TI  - The lost tribe: who cares?

PMID- 14677554
TI  - [Integrated critical care].

PMID- 14677555
TI  - [Integrated critical care].

PMID- 14677556
TI  - Proceedings of the Nobel Symposium No. 124. Septicemia and Shock: Pathogenesis
      and Novel Therapeutic Strategies. May 15-17, 2003, Stockholm, Sweden.

PMID- 14677557
TI  - Abstracts of the 48th Annual Meeting of the German Society for Neuropathology and
      Neuroanatomy. Berlin, Germany, October 8-11, 2003.

PMID- 14677558
TI  - Endocrine disruptors and the obesity epidemic.

PMID- 14677559
TI  - [Evaluation of the ototoxic action of aminoglycoside antibiotics (A.A.) on the
      inner ear by high frequency audiometry (HRA)].

PMID- 14677561
TI  - [10th Primary Prevention Forum, Youth Health Protection. 22 May 2003. Abstracts].

PMID- 14677560
TI  - Proceedings of the International Meeting, Ifosfamide: A Milestone Drug. Padua,
      Italy, February 17-18, 2003.

PMID- 14677562
TI  - New diagnostic test may help prevent deadly heart attacks in patients with acute
      coronary syndrome.

PMID- 14677563
TI  - COX-2 inhibitors reduce knee replacement surgery problems.

PMID- 14677564
TI  - Researchers call for new, independent federal agency to address health care
      quality and cost.

PMID- 14677565
TI  - Michigan consortium outlines multiple quality improvement findings for
      percutaneous coronary interventions.

PMID- 14677566
TI  - Wireless capsule endoscopy.
AB  - The Given M2A(R) ingestible, disposable imaging capsule contains a miniature
      video camera, which, when it is swallowed, can transmit images to a computer. It
      is used to detect abnormalities in the inner lining of the small intestine. In
      studies of small numbers of patients, the capsule demonstrates superior
      diagnostic rates for disorders of the small intestine among adults and children.
      All studies report fewer complications or less patient discomfort with the use of
      the capsule. Limiting factors are the time taken by physicians to evaluate the
      images, the lack of comparative evaluations of the capsule's sensitivity and
      specificity compared to conventional procedures and the impact of its cost.

PMID- 14677567
TI  - Masters of patient indexing. Interview by Jessica Squazzo.

PMID- 14677568
TI  - AHIMA in the 21st century: looking ahead.

PMID- 14677569
TI  - E-mail best practices maximize efficiency.

PMID- 14677570
TI  - Predicting skeletal maturation using cervical vertebrae.
AB  - This study's objective was to familiarize the profession with determining
      skeletal maturation and skeletal age, and predicting growth potential by using
      cervical vertebrae images of lateral cephalograms. The investigation was done
      through repeated evaluations of 30 randomly selected, pretreatment lateral
      cepaholometric radiographs. The accuracy of determining skeletal age and growth
      potential with lateral cephalograms was found to be R=0.98 (highly accurate) by
      statistical analysis.

PMID- 14677571
TI  - Lipoprotein metabolism in obesity and diabetes: insights from stable isotope
      kinetic studies in humans.
AB  - The paradigm of obesity leading to insulin resistance and type 2 diabetes is
      examined in relation to dyslipidemia, which typically consists of high levels of
      triglycerides (TG) and low levels of high-density lipoprotein (HDL). Kinetic
      studies with stable isotope-labeled amino acid precursors have shown that the
      development of visceral obesity, as well as type 2 diabetes, leads to
      overproduction of the apolipoprotein B-100 and TG in very low-density
      lipoproteins. Elevated plasma levels or increased flux of albumin-bound free
      fatty acids to the liver appear to be underlying metabolic events in this
      process. Low levels of HDL are due to increased catabolism, which can be related
      to TG enrichment.

PMID- 14677572
TI  - Role of policosanols in the prevention and treatment of cardiovascular disease.
AB  - Policosanols are a mixture of aliphatic alcohols derived from purified sugar
      cane. When administered at 5 to 20 mg/day, policosanols have been shown to
      decrease the risk of atheroma formation by reducing platelet aggregation,
      endothelial damage, and foam cell formation in animals. Additionally,
      policosanols have been shown to lower total and low-density lipoprotein (LDL)
      cholesterol levels by 13 to 23% and 19 to 31%, respectively, while increasing
      high-density lipoprotein (HDL) cholesterol from 8 to 29%. Policosanols are
      thought to improve lipid profiles by reducing hepatic cholesterol biosynthesis
      while enhancing LDL clearance. When compared with statins, policosanols exhibit
      comparable cholesterol-lowering effects at much smaller doses. The mixture is
      well tolerated when administered to animals; however, a more precise safety
      profile is needed for humans. In summary, policosanols are a promising resource
      in the prevention and therapy of cardiovascular disease (CVD), but these results
      need to be confirmed in independent laboratories.

PMID- 14677573
TI  - Angiogenesis inhibitors may regulate adiposity.
AB  - Overweight and obese are major health concerns owing to the complex co
      morbidities that inevitably follow. Diet and exercise are the primary means by
      which people attempt to lose weight. A recent study in an obese mouse model
      suggested that angiogenesis inhibitors, which are designed to inhibit tumor
      growth, are able to reduce adipose tissue mass by cutting off the blood supply.
      This approach may have application in the prevention and treatment of obesity by
      using foods with antiangiogenic potential.

PMID- 14677574
TI  - The function of the nuclear receptor peroxisome proliferator-activated receptor
      delta in energy homeostasis.
AB  - The metabolic function of the nuclear receptor peroxisome proliferator-activated
      receptor delta (PPAR(delta)) has been established by transfer of the PPAR(delta)
      gene into adipose tissue of mice in vivo and into adipocytes in culture.
      Investigators found that PPAR(delta) activation by such transfer leads to up
      regulation of energy expenditure by fatty acid oxidation. PPAR(delta) activation
      also results in lowered serum triglyceride and free fatty acid levels and
      decreased lipid accumulation. In vivo activation of PPAR(delta) in adipose tissue
      protects against obesity and fatty liver in mice fed a high-calorie diet.
      PPAR(delta) also activates the heat-producing uncoupling enzymes in brown adipose
      tissue (UCP1 and 3) and muscle (UCP2).

PMID- 14677575
TI  - A critical interaction: leptin and ghrelin.
AB  - Continuing research has increased our understanding of regulatory factors
      involving appetite, food intake, and energy metabolism. There appears to be a
      complex interaction among insulin, leptin, and ghrelin. A new study explored
      these interactions and indicates that leptin may regulate ghrelin levels and
      affect body weight changes.

PMID- 14677576
TI  - Olfactory bulbectomy: influences on maternal behavior in primiparous and
      multiparous rats.
AB  - Bilateral olfactory bulb ablation resulted in deficits in several components of
      maternal behavior in lactating, primiparous female rats. These females frequently
      cannibalized pups shortly after parturition. Furthermore, bilaterally
      bulbectomized, primiparous females spent less time nursing their pups and
      retrieved fewer pups than unilaterally bulbectomized or sham-operated females. In
      contrast to the situation in primiparous females, in multiparous females
      bilateral bulbectomy failed to influence any parameter of maternal behavior.

PMID- 14677577
TI  - Feedback training of 36 - 44 HZ EEG activity in the visual cortex and hippocampus
      of cats: evidence for sensory and motor involvement.
AB  - Milk reinforcement was contingent on the occurrence of 36 -44 (40) Hz EEG
      activity in the left visual cortex (VC) of one group of cats and in the right
      hippocampus (H) of a second group. Both groups learned to increase 40 Hz
      activity, and acquisition of reinforcement was associated with immobility. A
      third group (behavioral controls - BC) was trained by the method of successive
      approximation to behave in a similar manner to VC and H cats. Training
      significantly increased 40 Hz activity in all of the following structures, except
      the hippocampi of VC cats and between the right and left visual cortex of H and
      BC cats: posterior primary visual cortex (bilateral), anterior primary visual
      cortex (left), primary motor cortex (bilateral), dorsal hippocampus (bilateral),
      and midbrain reticular formation (bilateral). Since the behavioral and EEG
      changes of H and BC animals were similar, immobility appears to be important for
      increased hippocampal 40 Hz activity produced by feedback training. Testing in
      darkness enhanced 40 Hz activity in the trained area of VC cats but had no effect
      on H or BC animals. These results, in conjunction with the observation that VC
      cats appeared to visually fixate, suggest that VC cats may have learned to
      increase 40 Hz activity in the visual cortex by altering visual processing.

PMID- 14677578
TI  - Periodicity of death feigning by domestic fowl in response to simulated
      predation.
AB  - The presence and extent of periodicity in the manifestation of death feigning
      duration was assessed in 137 week-old White Leghorn chicks. Chicks were reared on
      an LD 12:12 regimen with light onset at 0800 hr. Each was tested only once at one
      of 13 clock hours spanning a 24 hr period. Death feigning duration varied
      significantly with clock hour of induction, being longest from 1300-1400 hr and
      briefest from 0600-1100 hr. Variability was also cyclic but was distributed
      bimodally, being greatest in the latter half of each L and D phase. There was no
      significant influence of management hour on death feigning duration. The adaptive
      significance of the periodicity for predator-prey interactions was discussed, as
      were methodological implications.

PMID- 14677579
TI  - Influence of maternal malnutrition on pituitary-adrenal responsiveness to
      offspring.
AB  - Maternal pituitary-adrenal responsiveness to noxious and pup-produced stimuli was
      investigated in rat mothers fed low protein or control diets. While low protein
      (LP) mothers did not differ from control (C) dams in basal secretion of
      corticosterone or in their response to ether or novelty stress, the LP mother's
      response to pups which had been either handled (H) or shocked (S) differed from
      controls. This responsiveness to pups depended on both the mother's and pup's
      nutritional condition. While control pups elicited a differential pattern of
      pituitary-adrenal response which depended on pup treatment (H/S) from both C and
      LP mothers, malnourished pups were not capable of eliciting this differential
      pattern from either type of dam. Overall, malnourished pups elicited less
      responsiveness. In addition, low protein mothers displayed a decreasing
      responsiveness toward malnourished pups as lactation proceeded. Thus, this
      physiological evidence confirms behavioral observations indicating that both the
      mother's and pup's nutritional condition play a role in determining mother-infant
      relationships.

PMID- 14677580
TI  - Plasma corticosterone levels as an index of the strength of illness induced taste
      aversions.
AB  - Data are presented which demonstrate the task generality of pituitary-adrenal
      changes that accompany avoidance conditioning. In two experiments a conditioned
      aversion to milk was established by pairing it with lithium chloride (LiCl). In
      Experiment 1 conditioned pituitary-adrenal activation occurred when, in a
      conflict situation, animals reexperienced milk that had earlier been paired with
      LiCl. The relationship between the strength of aversion and corticosterone levels
      was such that animals showing the greatest avoidance showed the largest
      elevations in plasma corticosterone. In Experiment 2 this behavior/steroid
      relationship was manipulated. Dexamethasone (DEX) pretreatment on the day of
      conditioning was used to attenuate the conditioned aversion. Compared to saline
      (SAL) controls when reexposed to milk, DEX animals showed an attenuated aversion
      (i.e., drank more) and a smaller conditioned response (i.e., less adrenocortical
      activity). The reduction of conditioned elevation in corticosterone was not due
      to any residual effects of DEX at the time of testing (Experiment 3). Plasma
      levels of corticosterone represent an index for assessing the strength of illness
      induced conditioned taste aversions.

PMID- 14677581
TI  - Effect of environmental lighting on sexual behavior and testosterone levels of
      female rats.
AB  - The effects of exposure to two different lighting regimes, constant light (LL)
      and cyclic light (LD) on the sexual performance and serum testosterone
      concentrations of intact, virgin, female rats was investigated. During copulatory
      pairing there were significant changes in the sexual performance of both LL and
      LD rats. Sexual receptivity in the LL females increased as a result of copulatory
      stimulation, whereas the sexual performance of LD females declined. Throughout
      copulatory testing the level of sexual receptivity displayed by the LL females
      was significantly less than that of the LD females. Testosterone levels in
      acyclic virgin LL rats were significantly lower than the levels in cycling,
      virgin, LD rats. The implications of these findings were discussed.

PMID- 14677582
TI  - Effects of additional cues on passive avoidance learning and extinction in rats
      with hippocampal lesions.
AB  - Following the acquisition of a water-rewarded approach response in a straight
      runway, the effects of introducing shock in the goal box (passive avoidance - PA)
      or withdrawing reinforcement (extinction) were compared in hippocampal, cortical,
      and operated control groups of rats. Under standard test conditions, hippocampal
      groups were impaired in PA learning and showed strong resistance to extinction,
      relative to the control groups. When additional cues were provided such that
      external stimuli associated with goal box events could be easily detected early
      in the runway, performance differences between the hippocampal and control groups
      were eliminated in the PA test and significantly reduced in extinction. The
      results emphasize the inefficient processing by hippocampally-damaged animals of
      stimulus cues following a shift in experimental contingencies.

PMID- 14677583
TI  - Effects of variations in copulatory behavior on pregnancy in two species of
      Peromyscus.
AB  - Stimulation requirements for the initiation of pregnancy were studied in cotton
      mice, Peromyscus gossypinus, and white-footed mice, P. leucopus. Mating to
      satiety rather than for one ejaculatory series significantly increased the per
      cent of P. gossypinus females pregnant (63% vs 0%). Among females mated to
      satiety, those which became pregnant received significantly more copulations than
      those which did not. While no P. leucopus female mated for one ejaculatory series
      became pregnant, the increase in the probability of pregnancy following tests
      continued to satiety (or satiety plus overnight) was not significant, as just 20%
      of females in the satiety groups became pregnant. The multiple ejaculation
      pattern in these species appears to be an integral part of pregnancy initiation.

PMID- 14677584
TI  - Electroencephalographic and reaction time asymmetries to musical chord stimuli.
AB  - EEG was recorded over left and right hemispheres at temporal leads (T3, T4)
      referred to the vertex (Cz) in 16 right-handed male subjects. Musical chords were
      presented randomly in monaural sequence, during a task which required a selective
      motor response to stimuli presented to one ear. The integrated amplitude of the 8
      13 Hz alpha rhythm was measured when subjects listened passively. Under all
      conditions, a lower mean alpha amplitude was recorded over the right hemisphere
      than the left, regardless of which ear was stimulated. Alpha suppression over the
      right temporal area was accentuated when the performance task directed attention
      to the stimulus. Reaction time to left ear stimulation was shorter than that for
      the right ear. With monaural stimulus presentation behavioral asymmetry, and
      various EEG asymmetries can be observed. There is hemispheric asymmetry
      associated with attention to task relevant stimuli indicated by reduction in the
      alpha rhythm over the right temporal area and asymmetry in reaction time with
      greater efficiency of the left ear to muscial chords.

PMID- 14677585
TI  - Variations in slow wave activity during sleep in the rat.
AB  - Scoring of human electroencephalogram (EEG) recordings usually includes
      subdivisions of non-rapid eye movement (NREM) sleep based on amount of slow wave
      activity. This procedure has revealed relationships between slow wave activity
      and many other variables. In animals, however, few experimenters have described
      variations in slow wave activity within NREM sleep. The present study quantifies,
      by filtering and integration techniques, variations in amount of slow wave
      activity during NREM sleep in the rat. Slow wave activity was found to be
      greatest at the start of the light period; the diurnal variation of slow wave
      activity within NREM sleep was correlated with variations in amount of NREM
      sleep. An amplitude criterion was used to define NREM sleep, but overall EEG
      amplitude during NREM sleep did not show the same diurnal variation as slow wave
      activity. The results indicate the value of measuring variations in slow wave
      amplitude during NREM sleep in animals in addition to overall EEG amplitude.

PMID- 14677586
TI  - Schedule-induced polydipsia: the role of oral and plasma factors.
AB  - To appreciate the contribution of oral and post-absorptive factors in the control
      of schedule-induced polydipsia (SIP), body fluid balance was determined at
      various times into the 4 hr session. Although dehydrated at the start of the
      session, rats quickly returned to normal balance which was maintained, despite
      excessive intake, by a brisk water diuresis. Plasma, as measured via the T-1824
      technique, was also normal. Gastric infusion of water following each pellet
      delivery failed to eliminate the polydipsia despite marked hemodilution, whereas,
      oral infusion of equivalent amounts of water completely abolished the phenomenon.
      Taken together, these results suggest that SIP is mediated by oropharyngeal
      rather than hydration controls.

PMID- 14677588
TI  - Orienting and classical conditioning in the rabbit (Oryctolagus cuniculus):
      effects of septal area lesions.
AB  - Rabbits with either sham or septal lesions recieved differential classical
      conditioning training in which tones of different frequencies served as CSs and
      paraorbital shock served as the UCS. Eyeblink (EB), EMG, and heart rate (HR) CRs
      were concommitantly assessed. Free field activity was also studied in selected
      animals. Animals with septal lesions revealed an impaired EB discrimination which
      resulted from increased responding to the CS-. These animals showed HR CRs of
      greater magnitude than sham animals. The HR discrimination was, however,
      unimpaired by septal lesions. Differential EMG activity also occurred, but was
      unaffected by septal destruction. Septal lesions resulted in greater free-field
      activity associated with visual stimulation, but no differences were obtained
      between septal and sham animals in the dark. It is suggested that these results
      were due to an enhanced reactivity to environmental stimulation, possibly related
      to dysfunctions of the orienting reflex.

PMID- 14677587
TI  - Subcortical nature of Pavlovian differentiation in the rabbit.
AB  - Normal, hemidecorticated and decorticated rabbits were trained to criterion in a
      Pavlovian light-tone differentiation situation using the nictitating membrane
      preparation. Neither hemidecortication nor total neodecortication had any
      significant effect on the acquisition of Pavlovian conditional responses and both
      types of lesion were accompanied by differentiation performance which was as good
      as, or better than, that shown by normal controls. There was an indication
      however, that total neodecortication produced a slight retardation in the initial
      acquisition of conditional responses to the positive conditional stimulus. Both
      hemidecortication and bilateral neodecortication increased conditional response
      onset latencies but did not affect unconditional response latencies. These data
      are consistent with the notion that the essential substrate for Pavlovian
      conditioning is subcortical and that the breadth of stimulus feature extraction
      is reduced by neodecortication. In the course of this study it was noted that
      neodecortication reduced the asymptotic body weight of animals in both the
      lesioned groups.

PMID- 14677589
TI  - Fimbria-fornix lesions and sexual-social behavior of the guinea pig.
AB  - Male and female guinea pigs were given fimbria-fornix lesions and their sexual
      social activity was compared to lesioned control animals. The lesions reduced the
      sexual and aggressive behavior of the male guinea pig. In the female, on the
      other hand, aggression towards the male increased during attempted copulation.
      Both experimental and control animals were given an open-field activity test. It
      was found that fimbria-fornix lesioned animals displayed less activity than did
      their control counterparts. These results were consistent with earlier findings
      and were related to previous observations of decorticate rats. It was suggested
      that the hippocampal output via the fimbria-fornix during sexual-social behavior
      plays a role in selecting motor patterns appropriate for the motivational state
      of the animal.

PMID- 14677590
TI  - Ovarian influences on food intake and body weight regulation in lactating rats.
AB  - In the following experiments, an attempt was made to determine the role of the
      ovary in the control of food intake and body weight regulation during lactation.
      In the first study, it was found that concentrations of estradiol benzoate
      effective in suppressing food intake and body weight in nonlactating animals were
      not effective during lactation. In the second experiment, ovariectomy during
      lactation was shown not to produce the usual increases in food intake and body
      weight or change in meal patterns known to occur after ovariectomy in the
      nonlactating rat. These results suggested that lactating animals behave the as
      though functionally ovariectomized and that the removal of the ovaries is of no
      additional consequence. The further observation that animals nursing small
      litters gained weight considerably more rapidly than animals nursing large
      litters led to the prediction that these animals would also be more responsive to
      the suppressive effects of EB. In the third study, EB in concentrations which are
      not effective in suppressing body weight in animals nursing large litters was
      found to suppress body weight in mothers with small litters. However, since these
      animals also showed a decline in milk yield, a number of alternative
      interpretations of these results were considered. These results, together with
      data concerning levels of ovarian hormones during gestation and lactation led to
      the hypothesis that pregnant and lactating animals undergo an elevation in body
      weight set-point, similar in magnitude and quality to elevations following
      ovariectomy in the nonlactating animal.

PMID- 14677591
TI  - Endocrine coordination in rhesus monkeys: female responses to the male.
AB  - Female rhesus monkeys were captured from the free-ranging colony at La Parguera,
      Puerto Rico during the non-mating season and paired with testosterone propionate
      treated and control males daily for 12 weeks. Testosterone propionate-treated
      males displayed high levels of sexual behavior and low levels of aggressive
      behavior compared to control males. Pairing females with such sexually active or
      inactive males had only minor effects on female sexual behavior and no measurable
      influence on ovarian cyclicity. These results indicate that sexual activity of
      males apparently failed to coordinate reproductive changes in females.
      Reproductive coordination previously reported in females may be due to
      interactions among females.

PMID- 14677592
TI  - Effects of bilateral amygdaloid lesions on gonadal and pituitary hormones in
      serum and on sexual behavior in female rhesus monkeys.
AB  - Bilateral lesions that destroyed the amygdaloid nuclear complex failed to alter
      either serum concentrations of luteinizing hormone (LH), estradiol (E2),
      progesterone, and testosterone or sexual behavior in female rhesus monkeys. In 3
      of 5 females ovulation occurred in the postoperative cycle, and in 4 of 5 females
      exogenous E2 treatment released a surge of LH whose pattern was indistinguishable
      from the normal preovulatory surge. A postcastration rise in serum LH also
      occurred in the 5 lesioned monkeys, and E2 again induced an LH release. The data
      suggest that the amygdala does not play a major role in regulation of LH or
      ovarian steroid secretion during the menstrual cycle. Moreover amygdaloid lesions
      in female monkeys do not alter their sexual behavior.

PMID- 14677593
TI  - Impaired temperature regulation in rats after anosmia induced peripherally or
      centrally.
AB  - Bilateral olfactory bulbectomy or destruction of the olfactory epithelium of rats
      resulted in elevated body temperature in room temperature, and lowered water/food
      ratio in 30 degrees ambient temperature. The results suggest the involvement of
      the olfactory system in the thermoregulation.

PMID- 14677594
TI  - Web-building time in a spider: preliminary applications of ultrasonic detection.
AB  - Data collection on time and length of building in orb-weaving spiders has
      suffered from absence of light during construction and inconvenient hours. A
      simple apparatus is described which permits recording of the spiders' movements
      as they disturb an ultrasonic field. By varying onset and length of dark periods
      for two animals at even temperature and by registering the building periods for
      127 webs, a definite influence of the light-dark cycle can be identified: there
      is a strong preference for building webs in the dark; this is superimposed on the
      circadian rhythm of orb-web construction. One of the spiders always built earlier
      than the other.

PMID- 14677595
TI  - The weanling rat ventromedial syndrome: males get just as fat as females.
AB  - Weanling female and male Holtzman rats received bilateral electroytic lesions in
      the ventromedial hypothalamic nucleus (VMN) at the age of 27 and 26 days,
      respectively. Sham-operated rats served as controls. The animals were maintained
      on a synthetic diet (4.2 Cal/g) and tap water ad lib, and body weight, Lee
      (obesity) Index, tail length and food and water intake were recorded weekly for 6
      weeks. The only parameters in which a significant sex difference could be
      demonstrated were body weight gains and water intake which were greater in the
      male VMN rats. Female and male VMN rats also utilized food energy for fat
      deposition, body weight and body length change to the same extent. The data also
      show that in growing animals, body weight is a poor criterion for the accurate
      assessment of obesity status and true growth.

PMID- 14677596
TI  - Techniques to prevent olfactory nerve reconstitution in the pigeon.
AB  - Transectioned olfactory nerves in birds can reestablish structural and functional
      connections with the olfactory bulbs in comparatively short time spans, thereby
      hampering long-range studies of avian olfaction and behavior. Accordingly,
      techniques are described that are suitable for impeding the reconstitution of the
      olfactory nerve after its transection in the pigeon. These involve the use of
      inexpensive and easily obtainable materials including cotton pellets, glass
      beads, and polyethylene tubing.

PMID- 14677597
TI  - Acquisition of schedule-induced polydipsia in rats with no prior drinking
      experience.
AB  - Three litters of 10 rat pups each were reared on Purina laboratory chow and
      either (1) continuous access to water, (2) access to both water and lettuce until
      weaning at 21 days and then only lettuce, or (3) continuous access to lettuce. At
      100 days all rats were reduced to 80% free feeding weight and tested for
      polydipsia. During 15 sessions of polydipsia testing, excessive postpellet
      drinking developed in all groups to 45 mg Noyes pellets delivered on a fixed-time
      1 min schedule. No significant differences in water intake over sessions were
      found among groups. It was concluded that schedule-induced polydipsia does not
      represent an exaggeration of a learned prandial drinking pattern, but rather an
      exaggeration of an inborn prandial drinking reflex.

PMID- 14677598
TI  - Disinhibition and external inhibition of response following septal lesions in
      rats.
AB  - Septal-lesioned and sham-operate rats were tested for reactivity to extraneous
      stimuli (clicks or flashing lights) presented during periods of low or high
      responding generated by a 120-sec FI schedule of reinforcement. While septal
      lesioned rats tended to show greater disinhibition and less external inhibition
      than sham-operates, the magnitude of the deficits was not considered sufficiently
      great to warrant the conclusion that the septal syndrome results from increased
      susceptibility to disinhibition.

PMID- 14677599
TI  - Effects of prepartal stress on postpartal nursing behavior, litter development
      and adult sexual behavior.
AB  - Sprague-Dawley rats were exposed to the stress of restraint, heat and bright
      lights three times daily from Days 14 to 22 of gestation. Because prepartal
      stress did not markedly disturb the mother's retrieving and crouching behavior,
      disturbances in postpartal nursing behavior do not seem to account for the
      abnormal sexual behavior of male offspring as adults. The most significant
      finding was that litter weights were reduced, not only at birth, but for 3 weeks
      thereafter, suggesting that prepartal stress not only altered the pups in utero
      but also affected postpartal milk synthesis. The possibility emerges that
      prepartal stress may alter adult sexual behavior in males by modifications in
      fetal and/or maternal pituitary glands.

PMID- 14677600
TI  - Viewing and sectioning the rat's optic nerve using cheap retractors.
AB  - A technique for sectioning the optic nerve in rats is described which permits
      direct viewing of the nerve during surgery. The technique results in no damage to
      the front of the eye. A procedure for constructing cheap, effective retractors is
      described.

PMID- 14677601
TI  - Rapid method for introducing fiberglass filaments into microelectrode capillary
      tubes.
AB  - Preparation of glass microelectrodes by insertion of fiberglass filaments, prior
      to pulling, can be facilitated by the use of a suction technique.

PMID- 14677602
TI  - Effects of ovariectomy and estradiol on body weight and food intake in gold
      thioglucose-treated mice.
AB  - Two experiments investigated the effects of ovariectomy and estradiol replacement
      on the body weight and food intake of mice that had previously been treated with
      either gold thioglucose or saline. Ovariectomy and estradiol benzoate injections
      altered food intake in gold thioglucose-treated mice as much as in saline
      controls. Ovariectomy increased body weight in saline controls but it was without
      effect on the body weight of gold thioglucose-treated mice.

PMID- 14677603
TI  - Chronic catheterization of the spinal subarachnoid space.
AB  - To administer drugs into the spinal subarachnoid space of unanesthetized and
      intact rats and rabbits, a procedure is described whereby a polyethylene catheter
      (PE-10) may be inserted through a puncture of the atlanto-occipital membrane and
      secured to the skull. Calibration experiments carried out with bromophenol blue
      dye, 3H-naloxone and 14C-urea revealed first, that there was little rostro-caudal
      diffusion of the injectate along the spinal axis and secondly, that even for
      compounds such as naloxone which can rapidly permeate neural tissues, the levels
      which do appear in the brain are small following the spinal subarachnoid
      administration of the drug. Control injections, administered either acutely or
      repeatedly over a prolonged period of time, had no detectable effect on the
      animal's behavior. These observations, as well as the lack of pathology in the
      spinal cords of rats having such catheters for periods of up to 4 months suggests
      that the implant is well tolerated.

PMID- 14677604
TI  - Nutritional variables and their effect on the development of ultrasonic
      vocalizations in rat pups.
AB  - Measures of ultrasonic vocalizations were made on alternate days during the first
      and second weeks postpartum in rat pups reared by mothers fed either control
      (23%) or low protein (8%) diets. Compared to those reared by control mothers,
      pups reared by low protein mothers emitted significantly fewer ultrasonic
      vocalizations. The hypothesis that malnutrition might shift the age at which peak
      rate of vocalizations were emitted was not confirmed.

PMID- 14677605
TI  - Coronally positioned flap with or without enamel matrix protein derivative for
      the treatment of gingival recessions.
AB  - PURPOSE: To evaluate, histometrically, the healing of gingival recessions treated
      by coronally positioned flaps associated with enamel matrix protein derivative
      (EMD-Group) and to compare it to that obtained with coronally positioned flaps
      alone (CPF-Group). METHODS: Five mongrel dogs were used. Gingival recessions were
      surgically created on the buccal aspect of the upper cuspids. The defects (5 x 7
      mm) were exposed to plaque accumulation for 3 months. After a preparation period,
      the contralateral defects were randomly assigned to each group. After 3 months of
      healing, the dogs were sacrificed and the blocks were processed. The histometric
      parameters evaluated included: gingival recession, length of epithelium, new
      connective tissue attachment and new bone. RESULTS: The gingival recession was 
      0.1 +/- 0.2 mm for the EMD-Group and -0.8 +/- 1.3 mm for the CPF-Group (P =
      0.17). The extension of the epithelium was 1.2 +/- 1.0 mm for the EMD-Group and
      1.3 +/- 0.7 mm for the CPF-Group (P = 0.89). The new connective tissue attachment
      was 4.8 +/- 0.7 in the EMD-Group and 4.0 +/- 1.4 in the CPF-Group (P = 0.22). The
      new bone was 0.1 +/- 1.8 mm and -0.5 +/- 1.4 mm in the EMD-Group and CPF-Group,
      respectively (P = 0.50). Histologically, the defect coverage observed was 98.2%
      for the EMD-Group and 85.8% for the CPF-Group.

PMID- 14677606
TI  - Microtensile bond strength of several adhesive systems to different dentin
      depths.
AB  - PURPOSE: To determine the bond strength of five adhesives systems to either
      superficial or deep dentin. METHODS: Extracted human third molars had their
      crowns transversally sectioned either next to the occlusal DEJ or next to the
      pulp, to expose flat, superficial or deep dentin surfaces. The surfaces were
      bonded with: 1) three two-step, total-etch, self-priming adhesives (Single Bond,
      Prime&Bond NT, and Excite), 2) a two-step, self-etching primer (Clearfil SE
      Bond), and 3) a single-step, self-etching all-in-one adhesive (Etch & Prime 3.0)
      according to manufacturers' directions. Composite build-ups were constructed
      incrementally with Z250. After storage for 24 hours in water at 37 degrees C, the
      teeth were sectioned to obtain several bonded beams of 1.0 mm2 cross-sectional
      area. Each beam was tested in tension in an Instron machine at 0.5 mm/minute.
      Results were analyzed by two-way ANOVA and post-hoc multiple comparisons (P =
      0.05). Bonded interfaces were also examined by TEM. Nanoleakage was examined
      using a silver-staining technique. RESULTS: Single Bond, Prime&Bond NT and
      Clearfil SE Bond performed equally when were bonded to superficial dentin; the
      lowest value was obtained with Etch & Prime 3.0. On deep dentin, the highest bond
      strengths were attained with Clearfil SE Bond and Prime & Bond NT. The bond
      strengths of Prime & Bond NT and Excite were significantly higher to deep than to
      superficial dentin and the rest of the adhesives showed similar bond strength to
      both dentin depths. Nanoleakage was manifested to variable extent within all
      hybrid layers examined.

PMID- 14677607
TI  - Bristle end rounding of manual toothbrushes and reproducibility of end rounding
      classification.
AB  - PURPOSE: To evaluate the bristle end rounding quality of the toothbrushes
      selected. Furthermore the reproducibility of the bristle tip classification
      method was assessed. METHODS: Fifteen different manual toothbrushes were examined
      by taking into account the traumatic potential of toothbrushing caused by sharp
      and edged bristle end geometry. Three brushes for young children (0-4 years of
      age), eight brushes for children of 5-14 years of age and four brushes for
      juveniles and adults were included. The macroscopic criteria to which the
      selected brushes had to conform were: a compact toothbrush handle, a small brush
      head with rounded contours and a medium or soft bristle stiffness. Bristle tip
      geometry was investigated under SEM according to a modified scale by Silverstone
      & Featherstone. End rounding was examined in five regions equally distributed
      over the brush head. Two brushes of each brand were included in the SEM
      investigation. For evaluation of reproducibility , end roundings of 119 bristle
      tips were assessed twice by one experienced examiner and once by two additional
      unexperienced examiners. RESULTS: The proportion of acceptably rounded bristle
      tips varied widely from 65.2 - 99%. Half of the products examined achieved a
      level of at least 90% acceptable bristle end rounding. Five of the toothbrushes
      examined had between 70 and 90% acceptable bristle end geometries, while two
      products had less than 70%. Intraindividual reproducibility regarding acceptable
      and unacceptable end rounding was 99.16%, interindividual reproducibility varied
      between 90.76% and 94.96%.

PMID- 14677609
TI  - Restoration of endodontically treated teeth without posts.
AB  - PURPOSE: To describe the treatment of a patient with a dismal oral situation
      after successful cure for drug addiction. METHODS: After root canal treatment and
      surgical pretreatment, four maxillary glass-fiber reinforced composite fixed
      partial dentures, anchored by endo-crowns instead of post and core, were
      fabricated (Targis & Vectris). Additionally, full crowns on four dental implants
      and an inlay were produced of non-reinforced composite (Targis). All restorations
      were luted adhesively to abutments with a three component adhesive system (Syntac
      Classic), light-curing composite (Tetric) and an ultrasonic insertion technique.
      RESULTS: An esthetic and functional acceptable result was achieved. Excessive
      removal of tooth structure by post preparation may weaken the root.

PMID- 14677608
TI  - Dose response efficacy of sodium fluoride dentifrice at 9 and 21 months with
      supervised brushing.
AB  - PURPOSE: To assess whether a fluoride dose response could be detected with a
      relatively small sample size in a short duration using a novel randomized, double
      blind study design. METHODS: Subjects (N = 644, with approximately 215 per group)
      with a mean age of 10.4 years old (9-12 years old) used a placebo dentifrice, an
      1100 ppm F dentifrice or a 2800 ppm F dentifrice for the first 9 months of the
      study. Subjects in the placebo group were then switched to either 1100 ppm or
      2800 ppm F dentifrice for the remainder of the study, while subjects in the
      fluoride groups continued with their original treatment assignments. Three
      calibrated examiners measured visual-tactile caries as DMFS that was supplemented
      with a radiographic examination at baseline, 9 months and 21 months for each
      subject. RESULTS: The results of this study are consistent with the previous
      results reported for sodium fluoride dentifrices. For all examiners, the 1100 ppm
      and 2800 ppm fluoride dentifrices delivered statistically significantly (P <
      0.05) lower DMFS scores than the placebo control dentifrice at 9 months, while at
      21 months the 1100 ppm and 2800 ppm fluoride dentifrices delivered statistically
      significantly lower DMFS scores compared to the both the placebo/1100 ppm and the
      placebo/2800 ppm dentifrice groups. In addition, one of the three examiners
      observed a directional (P = 0.11) dose response (2800 ppm F < 1100 ppm F) at 9
      months, while at 21 months all three examiners observed evidence of a dose
      response, with one examiner observing a statistically significant difference
      between 1100 ppm and 2800 ppm F. Caries scores on occlusal surfaces provided the
      strongest evidence of an 1100 ppm F vs. 2800 ppm F difference.

PMID- 14677610
TI  - Effect of light activation method on flexural properties of dental composites.
AB  - PURPOSE: To determine if irradiating composites in a laboratory tungsten-halogen
      light-curing unit produced equal flexural properties to stepwise hand-curing with
      a tungsten-halogen lamp. METHODS: Bars (n = 10) of nine commercial composites
      were formed by light-curing in square glass tubes (2 x 2 x 25 mm). Flexure
      strength (FS, MPa) and flexure modulus (FM, GPa) were tested in three-point
      bending after aging specimens in water at 37 degrees C for 1 day. Two methods
      were used to irradiate the composites: a) Triad II (Dentsply) using 40-second
      exposures from top and bottom; and b) Optilux 400 (Demetron; 600 mW/cm2) using 3
      x 40 seconds overlapping exposures from the top only. Filler wt% was determined
      by thermal gravimetric analysis. The degree of conversion (DC) of each composite
      cured with the two techniques was evaluated by micro-FTIR. T-tests were performed
      for FS and FM to compare Triad II vs Optilux for each composite (alpha < 0.05).
      RESULTS: There was a trend for Optilux to produce greater FS (significant for
      A110, Herculite and P60) and FM (significant for all but Clearfil, Esthet-X and
      Z250), but differences averaged less than 10%. There was no difference in DC
      between the irradiation modes for any composite.

PMID- 14677611
TI  - Effect of a LED versus halogen light cure polymerization on the curing
      characteristics of three composite resins.
AB  - PURPOSE: To evaluate the effect, in vitro, of a LED (GC E Light) versus an
      halogen (Astralis 7) polymerization on the mechanical properties of three
      commercially available microhybrid composite resins. METHODS: Three commercially
      available composite resins (Tetric Ceram, Charisma, and Z100), and six modes of
      polymerization were evaluated (one mode for Astralis (AST): HIP 40 seconds and
      five modes for the GC E Light (GCE): standard 40 seconds, fast cure 6 seconds,
      fast cure 12 seconds, soft cure A 39 seconds, and turbo 10 seconds) in terms of
      top surface and bottom surface (2 mm-depth) microhardness, and flexural strength.
      Five specimens of each composite resin were made for the two mechanical
      properties tested. Five hardness values were recorded on each side for each
      sample with a Vickers diamond indenter. A three point bending test was performed
      at a crosshead speed of 1 mm/minute. Statistical comparisons were made using a
      two-way ANOVA (composite resin, polymerization mode) and a Fisher's test (P <
      0.05). RESULTS: Z100 presented highest properties for both tests. Top surface
      microhardness: for Tetric Ceram and Charisma, the longer the exposure time, the
      higher the results, with no difference between AST mode and the longer GCE modes.
      For Z100, the highest values were obtained with AST. Whichever the material,
      short times (fast cure 6 seconds and turbo) exhibited poor results. Bottom
      surface microhardness: the samples cured with AST presented higher results but
      quite similar mechanical properties were achieved with the fast cure 12 GCE mode
      of the LED LCU. Fast cure 6 seconds and turbo obtained the lowest results.
      Flexural strength: the results were comparable with those obtained in bottom
      microhardness.

PMID- 14677612
TI  - Microtensile bond strength of eleven contemporary adhesives to enamel.
AB  - PURPOSE: To compare the microtensile bond strength (microTBS) to enamel of 10
      contemporary adhesives, including three one-step self-etch systems, four two-step
      self-etch systems and three two-step total-etch systems, with that of a
      conventional three-step total-etch adhesive. METHODS: Resin composite (Z100, 3M)
      was bonded to flat, #600-grit wet-sanded enamel surfaces of 18 extracted human
      third molars using the adhesives strictly according to the respective
      manufacturer's instructions. After storage overnight in 37 degrees C water, the
      bonded specimens were sectioned into 2-4 thin slabs of approximately 1 mm
      thickness and 2.5 mm width. They were then trimmed into an hourglass shape with
      an interface area of approximately 1 mm2, and subsequently subjected to microTBS
      testing with a cross-head speed of 1 mm/minute. RESULTS: The microTBS to enamel
      varied from 3.2 MPa for the experimental one-step self-etch adhesive PQ/Universal
      (self-etch) to 43.9 MPa for the two-step total-etch adhesive Scotchbond 1. When
      compared with the conventional three-step total-etch adhesive OptiBond FL, the
      bond strengths of most adhesives with simplified application procedures were not
      significantly different, except for two one-step self-etch adhesives,
      experimental PQ/Universal (self-etch) and One-up Bond F, that showed lower bond
      strengths. Specimen failures during sample preparation were recorded for the
      latter adhesives as well.

PMID- 14677613
TI  - Effect of drying methods on hybrid layer thickness.
AB  - PURPOSE: To evaluate the effect of drying methods used in scanning electron
      microscopy on the thickness of the hybrid layers created by several different
      adhesive systems. METHODS: A total etch dry bonding system, (Photobond), a three
      step bonding adhesive system, (Scotchbond Multi-Purpose), a wet-bonding adhesive
      system (All-Bond 2) and a self-etching primer system (Mac Bond II) were used in
      this study. To permit measurement of the thickness of the hybrid layer, the resin
      dentin interfaces were polished and etched briefly to remove polishing debris
      followed by immersion in 10% NaOCl for 4 hours. Half of the specimens in each
      group were subjected to fixation and critical-point drying followed by gold
      sputter-coating. The remaining specimens were allowed to air dry prior to gold
      sputter-coating. SEM observations were carried out to determine the structure and
      thickness of the hybrid layers. RESULTS: The thickness of hybrid layers were
      affected by the drying methods with the critical-point drying methods producing
      the thickest hybrid layers (P < 0.05). The thickest hybrid layers were created by
      Photobond, with Scotchbond Multi-Purpose and All-Bond 2 producing intermediate
      thickness hybrid layers, among the total etch systems. The thinnest hybrid layer
      among all of the adhesive systems was produced by the self-etching primer, Mac
      Bond II.

PMID- 14677614
TI  - Bonding of mild self-etching primers/adhesives to dentin with thick smear layers.
AB  - PURPOSE: To compare the microtensile bond strength (microTBS) and the
      ultrastructure of resin-dentin interfaces of four self-etching systems that were
      applied to dentin with thick smear layers. METHODS: Human third molars were
      ground with 180-grit silicon carbide papers to expose deep coronal dentin. A 3-mm
      vertical slit was made along the diameter of each tooth to fit a glass cover
      slip, dividing each tooth into two bonding surfaces. Two 2-step, self-etching
      primers (ABF experimental system and Imperva Fluoro Bond) and two single-step,
      self-etching adhesives (One-Up Bond F and AQ Bond) were examined. Adhesives were
      applied to one side of the teeth passively, and to the other side with continuous
      agitation for the same self-etching period. Incremental composite buildups were
      performed and beams with cross-sectional areas of 0.81 mm2 were prepared for
      microTBS evaluation. Demineralized, bonded specimens were processed for TEM
      examination. RESULTS: Two-way ANOVA showed that both the adhesive type and the
      application mode significantly affected microTBS results. However, the
      interaction of these two factors was not statistically significant (P > 0.05).
      For each adhesive, agitation produced significantly higher microTBS than passive
      application. With passive application, all systems diffused through thick smear
      layers and formed thin hybrid layers in intact dentin. With continuous agitation,
      smear layers were completely dispersed or dissolved, and thicker hybrid layers
      with upstanding collagen fibrils were observed.

PMID- 14677615
TI  - Effect of ion-exchange treatment on mechanical properties of new dental ceramics.
AB  - PURPOSE: To examine whether the ion exchange strengthening can be achieved for
      several new ceramics such as glass ceramics or castable ceramics. METHODS: The
      ceramics selected for this study were three porcelains and three castable
      ceramics. 60 bend bars of the respective ceramics (1 x 5 x 10 mm) were fabricated
      according to the respective manufacturer's directions. Finally, the respective
      specimens were polished up to 0.1 microm and then divided into two groups: one
      was coated with an ion-exchange paste and the other was not treated as the
      control. Then, for the respective ceramics the hardness, flexural strength and
      fracture toughness were investigated and compared to the control. RESULTS:
      Although the ion-exchange treatment significantly (P < 0.05, Scheffe's test)
      increased flexural strength and fracture toughness for the porcelain based
      ceramics, it did not increase these properties for the castable ceramics. The
      chemical treatment did not affect hardness for any of the specimens.

PMID- 14677616
TI  - Microleakage of resin-based liner materials and condensable composites using
      filled and unfilled adhesives.
AB  - PURPOSE: To evaluate the efficacy of differing resin based liner materials in
      reducing microleakage. METHODS: 80 freshly extracted caries-free human premolars
      and molars were used. MO/DO Class II standardized preparations were performed
      with the gingival margin placed 1 mm above the CEJ. Teeth were randomly divided
      into two groups; each one was divided into four subgroups (A-B-C-D for Group 1
      and E-F-G-H for Group 2). Each prepared tooth was etched with 32% H3PO4 (Uni
      Etch); in Group 1, one coat of One Step and in Group 2, two coats and two cures
      of Prime & Bond NT adhesives were applied. In each group 1 mm layer of three
      different liners was used: A2 Heliomolar RO for A and E; A2 Heliomolar Flow for B
      and F; A2 Bisfil 2B for C and G. No liner was used for D and H subgroups. Teeth
      were then restored using 2 mm increments of Pyramid A2 Dentin and A1 Enamel and
      cured with a VIP curing light. Teeth were thermocycled x500 between 5 degrees C
      and 55 degrees C with a dwell of 30 seconds and then placed in a 0.5% methylene
      blue dye solution for 24 hours at 37 degrees C. Samples were sectioned
      longitudinally and evaluated for microleakage at the gingival margin under a
      stereomicroscope at x20 magnification. Dye penetration was scored using an
      Ordinal Scoring System where 0= no penetration; 1= enamel penetration; and 2=
      dentin penetration. RESULTS: A Chi Square Test revealed a statistically
      significant difference between Group 1 and Groups 2 (P < 0.001). Group 1 yielded
      the most microleakage. No statistically significant difference was noted between
      the subgroups of each group; a statistically significant difference of B and D
      vs. E and H (P < 0.01 > 0.001) and B vs. G and D (P < 0.05 > 0.01) was also
      noted. The dentin bonding agent in Group 2 contributed to a reduction of
      microleakage when compared to Group 1.

PMID- 14677618
TI  - Leadership skills and team development. Part III of the dental management pyramid
      series.
AB  - Mastering the second layer of the Management Pyramid demands the dentist take on
      an active leadership role, clarify the practice vision, outline specific goals
      for the team to achieve then proceed to motivate each team member. Leadership
      affords the dentist the opportunity to ensure all actions and decisions work in
      unison to move the practice toward his goals.

PMID- 14677617
TI  - Enamel demineralization inhibition by cements at orthodontic band margins.
AB  - PURPOSE: To examine the demineralization inhibition effects of glass ionomer
      cement and polyacid-modified resin-based composite cement, in comparison to non
      fluoride releasing zinc phosphate cement. METHODS: Twenty-seven extracted molars
      were obtained and randomly assigned to three groups. An orthodontic band was
      sized and cemented using one of three cements. The teeth were painted with an
      acid-protective varnish, excluding a 1 mm area gingival to the orthodontic band.
      The teeth were placed in separate closed environments of a non-fluoridated acid
      challenge to induce demineralization for 5 days. The teeth were then sectioned
      two times buccolingually and two times mesiodistally. The sections were
      photographed with polarized light microscopy in an imbition media of water. The
      body of each lesion was measured with a computerized imaging system. The areas of
      the lesions, from each cement group, were compared. RESULTS: An analysis of
      variance (ANOVA) indicated significance in variance among groups (P < 0.001).
      Results of a multiple comparison analysis demonstrated significantly less
      demineralization adjacent to the glass ionomer cement group compared with the
      polyacid-modified resin cement group and non-fluoride releasing zinc phosphate
      control group (P < 0.05). There was no significant difference in adjacent
      demineralization inhibition between the zinc phosphate cement group and polyacid
      modified resin cement group (P < 0.05).

PMID- 14677619
TI  - An open-label study of the effects of a 24-day regimen of gestodene 60
      microg/ethinylestradiol 15 microg on endometrial histological findings in healthy
      women.
AB  - OBJECTIVES: This open-label, non-comparative study was conducted at a single
      center to evaluate the effects on the endometrium of a 24-day regimen of a
      combined oral contraceptive containing gestodene (GTD) 60 microg and
      ethinylestradiol (EE) 15 microg. METHODS: Healthy parous women who were > or = 18
      years old and had had regular menstrual cycles for the prior 3 months were
      randomly assigned to one of two groups. Subjects in group A underwent endometrial
      biopsies during the late luteal phase of the pretreatment cycle and between days
      15 and 24 of cycle 6. Subjects in group B had biopsies between days 15 and 24 of
      cycle 3 and during the late luteal phase of the post-treatment cycle. GTD 60
      microg/EE 15 microg was taken for the first 24 days of a 28-day cycle, followed
      by placebo pills for 4 days, for a total of six cycles. RESULTS: Data from 27
      women were included in the analyses. Eleven of the 13 evaluable baseline biopsies
      were classified as secretory. Three of nine subjects with evaluable biopsies at
      cycle 3 and four of nine subjects with evaluable biopsies at cycle 6 had an
      atrophic endometrium. Post-treatment biopsies showed a typical secretory
      endometrium in seven of 11 subjects with evaluable biopsies. CONCLUSIONS: The
      results of this study show that the 24-day regimen of GTD 60 microg/EE 15 microg
      produced effective endometrial suppression.

PMID- 14677620
TI  - The safety and contraceptive efficacy of a 24-day low-dose oral contraceptive
      regimen containing gestodene 60 microg and ethinylestradiol 15 microg.
AB  - OBJECTIVE: The safety and contraceptive efficacy of a new 24-day regimen of an
      oral contraceptive combination containing gestodene (GTD) 60 microg and
      ethinylestradiol (EE) 15 microg was evaluated in an open-label, multicenter
      study. METHODS: Adult women received GTD 60 microg/EE 15 microg from day 1 to 24
      and 4 days of placebo during a 28-day cycle for either 13 or 19 cycles. RESULTS:
      Of the 1515 subjects enrolled, 1496 were included in the intent-to-treat
      analysis. A total of three pregnancies were reported during the 18 194 treatment
      cycles of the study, yielding a Pearl index of 0.21. Life-table analysis, based
      on 16 954 cycles, gave an accidental pregnancy rate of 0.0033. The most frequent
      adverse events were headache (reported in 35% of subjects), absence of bleeding
      (16%), flu-like syndrome (15%), pharyngitis (15%) and abdominal pain (15%). The
      most frequent reasons for withdrawal from the study were metrorrhagia, flu
      syndrome and absence of bleeding. Analyses of withdrawal and intermenstrual
      bleeding and spotting indicated acceptable cycle control. CONCLUSIONS: The 24-day
      GTD 60 microg/EE 15 microg regimen appears to be a well-tolerated and effective
      method for low-dose oral contraception. The current formulation offers an ultra
      low steroidal dosage combined with a reduced pill-free interval to improve
      contraceptive efficacy.

PMID- 14677621
TI  - Cycle control, safety and efficacy of a 24-day regimen of gestodene 60 microg/
      ethinylestradiol 15 microg and a 21-day regimen of desogestrel 150
      microg/ethinylestradiol 20 microg.
AB  - OBJECTIVE: This multicenter, open-label study was conducted to compare the cycle
      control, efficacy and safety of a 24-day regimen of a new ultra-low-dose oral
      contraceptive containing gestodene (GTD) 60 microg/ethinylestradiol (EE) 15
      microg and a 21-day regimen of desogestrel (DSG) 150 microg/EE 20 microg.
      METHODS: Healthy women at least 18 years of age who had had regular menstrual
      cycles for the prior 3 months were randomly assigned to treatment for six cycles.
      RESULTS: Data from 1074 women were included in the analyses. Overall, 65% of
      cycles were normal with GTD/EE and 78% with DSG/EE. The overall incidence of
      breakthrough bleeding and/or spotting was 29% with GTD/EE and 20% with DSG/EE,
      with absence of bleeding occurring in 6% of cycles in the GTD/EE group and 1% of
      cycles in the DSG/EE group. The GTD/EE group had a significantly shorter length
      of bleeding episodes (4 vs. 5 days, p < 0.001), a significantly lower intensity
      of bleeding (p < 0.01) and a significantly shorter time for onset of withdrawal
      bleeding than the DSG/EE group (p < 0.001). Safety profiles for the two treatment
      groups were similar. Significantly more subjects in the DSG/ EE group withdrew
      because of breast pain (p = 0.03) and nausea or vomiting (p = 0.05). One
      pregnancy occurred in each treatment group. CONCLUSIONS: The 24-day regimen of
      GTD 60 microg/EE 15 microg provided good efficacy, acceptable cycle control and a
      favorable safety profile compared with DSG/EE. This ultra-low-dose formulation
      offers unique advantages in efficacy and safety for oral contraception.

PMID- 14677622
TI  - A comparative study of the effects of gestodene 60 microg/ethinylestradiol 15
      microg and desogestrel 150 microg/ethinylestradiol 20 microg on hemostatic
      balance, blood lipid levels and carbohydrate metabolism.
AB  - OBJECTIVES: This multicenter, randomized, parallel-group, open-label study was
      conducted to compare the effects of gestodene (GTD) 60 microg/ethinylestradiol
      (EE) 15 microg and desogestrel (DSG) 150 microg/EE 20 microg (Mercilon) on
      selected metabolic measurements during six cycles in 124 healthy women. METHODS:
      GTD/EE subjects received a single pill once daily from days 1 to 24 of a 28-day
      cycle, followed by placebo pills daily for the last 4 days of the cycle. DSG/EE
      subjects received a single pill daily from days 1 to 21 of a 28-day cycle,
      followed by a 7-day pill-free interval. Safety was assessed from changes in
      hemostatic measurements, lipid profile, glucose tolerance and adverse events.
      RESULTS: Both GTD/EE and DSG/EE groups exhibited minimal effects on the lipid
      profile. An increased glucose response was noted with both treatments and an
      increased insulin response was noted with GTD/EE. Hemostatic activity was
      increased in both groups but a counteracting increase in fibrinolytic activity
      occurred together with an increase in coagulatory activity. The incidence of
      adverse events was comparable between groups, and no significant differences in
      cycle control were observed between groups. No pregnancies occurred in either
      group. CONCLUSIONS: The 24-day GTD 60 microg/EE 15 microg formulation and DSG/EE
      produced similar effects on hemostatic balance, lipid metabolism and glucose
      tolerance, and exhibited comparable efficacy and tolerability.

PMID- 14677623
TI  - Technical Bulletin no. 2003-03: freezing of microbial samples prior to testing.
      Parenteral Drug Association.

PMID- 14677624
TI  - Some further comments on aseptic processing guidance, or the fool on the hill:
      Parenteral Drug Association.

PMID- 14677625
TI  - Experimental determination of the pore size of filters. 1923.

PMID- 14677626
TI  - The "bubble-point equation" revisited.

PMID- 14677627
TI  - Effect of high-density lipoprotein associated cyclosporine on hepatic metabolism
      and renal function.
AB  - Cyclosporine (CSA), in both humans and animals, is associated with plasma
      lipoproteins. It has been demonstrated that CSA-lipoprotein association is partly
      responsible for the distribution and toxicity related to CSA use. Altered plasma
      lipoprotein profiles are often seen in transplantation recipients undergoing CSA
      treatment. In the present study, daily 0.1 mg/kg intravenous injections of either
      high-density lipoprotein-associated CSA (HDL-CSA), plasma-associated CSA (Plasma
      CSA), or CSA in Cremophor (CSA) were administered to adult male rats for 14 days.
      Vehicle controls included daily administrations of 0.5 ml/kg of Cremophor or
      saline. Serum creatinine levels, a marker of renal function, increased in rats
      administered Plasma-CSA as compared with control rats treated with CSA. CYP3A and
      CYP2C11 protein expression was suppressed by 27% and 39%, respectively, in the
      HDL-CSA treatment group and by 38% and 40% in the Plasma-CSA treated group as
      compared with CSA controls. In addition, 6beta-hydroxytestosterone, a marker of
      CYP3A activity, was reduced by 33% and 34% in the HDL-CSA and the Plasma-CSA
      treatment groups, respectively, as compared with the CSA control group. CYP2C11
      activity was measured by the in vitro formation of 2alpha-hydroxytestosterone.
      Activity levels in rats treated with HDL-CSA and Plasma-CSA were slightly induced
      as compared to CSA controls, however these differences were not found to be
      statistically significant. In summary, Plasma-CSA treatment resulted in renal
      dysfunction and suppressed CYP3A and CPY2C11 protein expression. These results
      demonstratethat intravenous lipoprotein-associated CSA alters the metabolism of
      CSA in the rat differently than CSA alone.

PMID- 14677628
TI  - The role of excipients and package components in the photostability of liquid
      formulations.
AB  - A phenyl ether-based drug substance exhibits photochemical degradation in citrate
      buffers with both ultraviolet (300-450 nm range) and visible light (380-700 nm
      range) exposure, even though the drug molecule itself is non-light absorbing at
      wavelengths > 300 nm. The major contributors to the observed photosensitivity are
      the citrate buffer, parts per billion (ppb) levels of iron, oxygen, and light
      exposure level. Although a primary phenol photodegradate is generated, there are
      at least eight other species formed as well. The molecular weights and abundance
      of these species suggest that the product distribution is generated by the
      reaction of hydroxyl radicals with the drug substance. The generation of the
      primary photodegradate is linearly proportional to the light exposure amount for
      a fixed concentration of iron present in the formulation. Conversely, the amount
      of photodegradation is also nearly linear with iron concentration (through 200
      ppb levels) for a fixed amount of light exposure. The proposed mechanism for the
      photochemical generation of hydroxyl radicals has precedence in the literature
      for similar combinations of iron, oxygen, carboxylate buffers, and light. Since
      the buffer salt and oxygen molecular equivalents in the product are significantly
      higher than the ppb levels of iron employed and more difficult to remove, the
      control of the extent of photodegradation largely rests on the control of trace
      levels of iron in the formulated product and control of light exposure. Exposure
      of drug solutions to a series of transition metals clearly indicates that iron is
      the key transition metal involved in the observed photochemistry. At manufacture,
      the primary source of iron is the raw materials (water, drug or excipients) used
      in the formulation. The level of iron for product stored in glass increases with
      sample age and can be attributed to iron leaching from borosilicate glass vials.
      Consideration of adequate light control during the manufacturing and packaging
      processes will be discussed and can only be defined as a function of the amount
      of iron present at the time of manufacture in the formulation. The generality of
      this chemistry to other drug candidates and in the presence of other common
      buffers will also be discussed.

PMID- 14677629
TI  - Statistical evaluation of stability data: criteria for change-over-time and data
      variability.
AB  - In a recently issued ICH Q1E guidance on evaluation of stability data of drug
      substances and products, the need to perform a statistical extrapolation of a
      shelf-life of a drug product or a retest period for a drug substance is based
      heavily on whether data exhibit a change-over-time and/or variability. However,
      this document suggests neither measures nor acceptance criteria of these two
      parameters. This paper demonstrates a useful application of simple statistical
      parameters for determining whether sets of stability data from either accelerated
      or long-term storage programs exhibit a change-over-time and/or variability.
      These parameters are all derived from a simple linear regression analysis first
      performed on the stability data. The p-value of the slope of the regression line
      is taken as a measure for change-over-time, and a value of 0.25 is suggested as a
      limit to insignificant change of the quantitative stability attributes monitored.
      The minimal process capability index, Cpk, calculated from the standard deviation
      of the regression line, is suggested as a measure for variability with a value of
      2.5 as a limit for an insignificant variability. The usefulness of the above two
      parameters, p-value and Cpk, was demonstrated on stability data of a refrigerated
      drug product and on pooled data of three batches of a drug substance. In both
      cases, the determined parameters allowed characterization of the data in terms of
      change-over-time and variability. Consequently, complete evaluation of the
      stability data could be pursued according to the ICH guidance. It is believed
      that the application of the above two parameters with their acceptance criteria
      will allow a more unified evaluation of stability data.

PMID- 14677630
TI  - Determination of conditions for the production scale sterilization of prefilled
      syringes.
AB  - External and internal differences in pressure of prefilled syringes can cause
      plunger movement during sterilization, which might cause drug product
      contamination. Consequently the pressure inside the autoclave during
      sterilization should be controlled carefully to prevent contamination of the drug
      product by microorganism and particulates. A previously determined theoretical
      relationship of temperature to pressure in sealed bottles was modified for
      prefilled syringes to take plunger movement into account. This modification
      yielded a correction factor that includes a coefficient of linear thermal
      expansion for the syringe, thermal expansion of the plunger, and friction between
      the plunger and the syringe wall. To confirm the accuracy of this modified
      relationship, 100 mL polypropylene prefilled syringes with butyl rubber plungers,
      some of which carried pressure and temperature sensors, were used to test various
      sterilization conditions at the experimental scale. The results showed that the
      major problem in establishing the pressure conditions for production scale
      sterilization is temperature distribution throughout the load. However, an over
      pressure sterilization cycle at 121 degrees C and 0.34 MPa showed the best
      results. Microbial challenge and light-obscuration particle count tests were
      performed on the syringes from the worst-case location predicted from modified
      relationship; the results show that these conditions preserved the sterility of
      the drug product and protected it from particulate contamination.

PMID- 14677631
TI  - Oxygen accelerates the accumulation of mutations during the senescence and
      immortalization of murine cells in culture.
AB  - Oxidative damage is a causal factor in aging and cancer, but it is still not
      clear how DNA damage, the cellular responses to such damage and its conversion to
      mutations by misrepair or misreplication contribute to these processes. Using
      transgenic mice carrying a lacZ mutation reporter, we have previously shown that
      mutations increase with age in most organs and tissues in vivo. It has also been
      previously shown that mouse cells respond to oxidative stress, typical of
      standard culture conditions, by undergoing cellular senescence. To understand
      better the consequences of oxidative stress, we cultured mouse embryo fibroblasts
      (MEFs) from lacZ mice under physiological oxygen tension (3%) or the high oxygen
      tension (20%) associated with standard culture, and determined the frequency and
      spectrum of mutations. Upon primary culture, the mutation frequency was found to
      increase approximately three-fold relative to the embryo. The majority of
      mutations were genome rearrangements. Subsequent culture in 20% oxygen resulted
      in senescence, followed by spontaneous immortalization. Immortalization was
      accompanied by an additional three-fold increase in mutations, most of which were
      G:C to T:A transversions, a signature mutation of oxidative DNA damage. In 3%
      oxygen, by contrast, MEFs did not senesce and the mutation frequency and spectrum
      remained similar to primary cultures. These findings demonstrate for the first
      time the impact of oxidative stress on the genomic integrity of murine cells
      during senescence and immortalization.

PMID- 14677632
TI  - Real-time imaging of transcriptional activation in live cells reveals rapid up
      regulation of the cyclin-dependent kinase inhibitor gene CDKN1A in replicative
      cellular senescence.
AB  - Cellular replicative senescence is a permanent growth arrest state that can be
      triggered by telomere shortening. The cyclin-dependent kinase (Cdk) inhibitor
      p21(CIP1/WAF1) (p21), encoded by the CDKN1A gene, is a critical cell cycle
      regulator whose expression increases as cells approach senescence. Although the
      pathways responsible for its up-regulation are not well understood, compelling
      evidence indicates that the upstream triggering event is telomere dysfunction.
      Studies of replicative senescence have been complicated by the asynchrony of its
      onset, which is caused by the continuous and stochastic variability in individual
      cell lifespans. In fact, the actual entry into senescence has never been observed
      in a single unperturbed cell. We report here a new in vitro human model system
      that allows entry into senescence to be monitored in real-time in individual
      viable cells. We used homologous recombination to generate non-immortalized
      fibroblast cells with the enhanced yellow fluorescence protein (EYFP) gene
      knocked into one CDKN1A gene copy, allowing promoter activity to be visualized as
      fluorescence intensity. Gamma irradiation, DNA-damaging drugs, expression of
      p14(ARF) or oncogenic Ras, and replicative exhaustion all resulted in elevated
      EYFP expression, demonstrating its proper control by physiological signalling
      circuits. Analysis by time-lapse microscopy of cultures approaching replicative
      senescence revealed that p21 levels rise abruptly in individual aging cells and
      remain elevated for extended periods of time.

PMID- 14677634
TI  - Oxidative stress in Caenorhabditis elegans: protective effects of superoxide
      dismutase/catalase mimetics.
AB  - The lifespan of Caenorhabditis elegans can be extended by the administration of
      synthetic superoxide dismutase/ catalase mimetics (SCMs) without any effects on
      development or fertility. Here we demonstrate that the mimetics, Euk-134 and Euk
      8, confer resistance to the oxidative stress-inducing agent, paraquat and to
      thermal stress. The protective effects of the compounds are apparent with
      treatments either during development or during adulthood and are independent of
      an insulin/IGF-I-like signalling pathway also known to affect thermal and
      oxidative stress resistance. Worms exposed to the compounds do not induce a
      cellular stress response and no detrimental effects are observed.

PMID- 14677633
TI  - Fast anterograde transport of herpes simplex virus: role for the amyloid
      precursor protein of alzheimer's disease.
AB  - Anterograde transport of herpes simplex virus (HSV) from its site of synthesis in
      the neuronal cell body out the neuronal process to the mucosal membrane is
      crucial for transmission of the virus from one person to another, yet the
      molecular mechanism is not known. By injecting GFP-labeled HSV into the giant
      axon of the squid, we reconstitute fast anterograde transport of human HSV and
      use this as an assay to uncover the underlying molecular mechanism. HSV travels
      by fast axonal transport at velocities four-fold faster (0.9 microm/sec average,
      1.2 microm/sec maximal) than that of mitochondria moving in the same axon (0.2
      microm/sec) and ten-fold faster than negatively charged beads (0.08 microm/sec).
      Transport of HSV utilizes cellular transport mechanisms because it appears to be
      driven from inside cellular membranes as revealed by negative stain electron
      microscopy and by the association of TGN46, a component of the cellular secretory
      pathway, with GFP-labeled viral particles. Finally, we show that amyloid
      precursor protein (APP), a putative receptor for the microtubule motor, kinesin,
      is a major component of viral particles, at least as abundant as any viral
      encoded protein, while another putative motor receptor, JIP 1/2, is not detected.
      Conventional kinesin is also associated with viral particles. This work links
      fast anterograde transport of the common pathogen, HSV, with the
      neurodegenerative Alzheimer's disease. This novel connection should prompt new
      ideas for treatment and prevention strategies.

PMID- 14677635
TI  - Juvenile diet restriction and the aging and reproduction of adult Drosophila
      melanogaster.
AB  - Mutations of the insulin signal pathway in Drosophila melanogaster produce long
      lived adults with many correlated phenotypes. Homozygotes of insulin-like
      receptor (InR) and insulin-like receptor substrate (chico) delay time to
      eclosion, reduce body size, decrease reproduction and increase life span. Because
      these mutations are expressed through all life stages it is unclear when insulin
      signals must be reduced to increase life span. As a first analysis of this
      problem in D. melanogaster we have manipulated the larval diet to determine if
      changes in metabolic regulation at this stage are sufficient to slow aging. We
      controlled the dietary yeast fed to third instar larvae and studied the size,
      mortality, fecundity and hormones of the resulting adults, which were fed a
      normal, yeast-replete diet. Adults from yeast-deprived larvae phenocopied many
      traits of InR and chico mutants: small body size, delayed eclosion, reduced
      ovariole number and reduced age-specific fecundity. But unlike constitutive
      mutants of the insulin/IGF system, adults from yeast-deprived larvae had normal
      patterns of demographic senescence, and this was accompanied by normal insulin
      like peptide and juvenile hormone syntheses. Surprisingly, the normal aging in
      these adults was also associated with greatly reduced fecundity. Although
      nutritional conditions of the larvae can affect the subsequent body size and
      fecundity of adults, these are not sufficient to slow aging.

PMID- 14677636
TI  - The effects of dietary coenzyme Q on Drosophila life span.
AB  - Reactive oxygen species (ROS), generated as by-products of aerobic metabolism,
      cause damage to proteins and cellular membranes, and are thus thought to
      influence senescence. Caenorhabditis elegans fed on diets lacking in ubiquinone
      coenzyme Q (CoQ), a coenzyme in the oxidative phosphorylation pathway, show
      increased longevity, possibly because of reduced ROS generation. We test the role
      of dietary CoQ in determining Drosophila melanogaster longevity by measuring
      survival and cytochrome c-oxidase activity (a proxy for aerobic metabolic
      performance) in flies fed wild-type yeast, CoQ-less yeast, or respiratory control
      (RC) yeast replete with CoQ but independently deficient in mitochondrial
      respiration. We find no evidence that dietary manipulation of CoQ in D.
      melanogaster increases life span or decreases age-dependent decline in cytochrome
      c oxidase activity. Instead, we find evidence that flies fed a diet of
      respiratory-deficient yeast (CoQ-less or RC) tend to have decreased longevity and
      increased rates of decline in cytochrome c-oxidase activity [corrected]

PMID- 14677637
TI  - A new method for estimating the importance of hydrogen-bonding groups in the
      binding site of a protein.
AB  - We introduce a new method to estimate the importance of hydrogen-bonding
      sitepoints in the binding site of a protein as part of a structure-based design
      strategy. Our method identifies hydrogen-bonding sitepoints within a binding
      pocket and ranks them according to both the accessibility of their hydrogen
      bonding regions to incoming ligands and their hydrogen-bonding strength. The
      combination of these components produces a prioritised list of sitepoints that
      are more likely to be involved in hydrogen bonding with an incoming ligand. A
      dataset of known protein-ligand interactions was used to compare the
      prioritisation of sitepoints identified by our method with those observed to be
      engaged in hydrogen bonding in their crystal structures. Our method was able to
      remove those sitepoints unable to bind the ligand due to a low accessibility or
      an unfavourable orientation and to award significantly higher hydrogen-bonding
      ranking values to those sitepoints observed to form hydrogen bonds. Our method
      can thus be used to identify hydrogen-bonding sitepoints that should be targeted
      preferentially in a drug design strategy.

PMID- 14677638
TI  - Prediction of blood-brain barrier permeation using quantum chemically derived
      information.
AB  - A model for the prediction of the blood-brain distribution (logBB) is obtained by
      multiple regression analysis of molecular descriptors for a training set of 90
      compounds. The majority of the descriptors are derived from quantum chemical
      information using semi-empirical AM1 calculations to compute fundamental
      properties of the molecules investigated. The polar surface area of the compounds
      can be described appropriately by six descriptors derived from the molecular
      electrostatic potential. This set shows a strong correlation with the observed
      logBB. Additional quantum chemically computed properties that contribute to the
      final model comprise the ionization potential and the covalent hydrogen-bond
      basicity. Complementary descriptors account for the presence of certain chemical
      groups, the number of hydrogen-bond donors, and the number of rotatable bonds of
      the compounds. The quality of the fit is further improved by including variables
      derived from principal component analysis of the molecular geometry.

PMID- 14677639
TI  - A Bayesian molecular interaction library.
AB  - We describe a library of molecular fragments designed to model and predict non
      bonded interactions between atoms. We apply the Bayesian approach, whereby prior
      knowledge and uncertainty of the mathematical model are incorporated into the
      estimated model and its parameters. The molecular interaction data are
      strengthened by narrowing the atom classification to 14 atom types, focusing on
      independent molecular contacts that lie within a short cutoff distance, and
      symmetrizing the interaction data for the molecular fragments. Furthermore, the
      location of atoms in contact with a molecular fragment are modeled by Gaussian
      mixture densities whose maximum a posteriori estimates are obtained by applying a
      version of the expectation-maximization algorithm that incorporates
      hyperparameters for the components of the Gaussian mixtures. A routine is
      introduced providing the hyperparameters and the initial values of the parameters
      of the Gaussian mixture densities. A model selection criterion, based on the
      concept of a 'minimum message length' is used to automatically select the optimal
      complexity of a mixture model and the most suitable orientation of a reference
      frame for a fragment in a coordinate system. The type of atom interacting with a
      molecular fragment is predicted by values of the posterior probability function
      and the accuracy of these predictions is evaluated by comparing the predicted
      atom type with the actual atom type seen in crystal structures. The fact that an
      atom will simultaneously interact with several molecular fragments forming a
      cohesive network of interactions is exploited by introducing two strategies that
      combine the predictions of atom types given by multiple fragments. The accuracy
      of these combined predictions is compared with those based on an individual
      fragment. Exhaustive validation analyses and qualitative examples (e.g., the
      ligand-binding domain of glutamate receptors) demonstrate that these improvements
      lead to effective modeling and prediction of molecular interactions.

PMID- 14677640
TI  - New designs for MRI contrast agents.
AB  - New designs for Magnetic Resonance Imaging contrast agents are presented.
      Essentially, they all are host-guest inclusion complexes between y-cyclodextrins
      and polyazamacrocycles of gadolinium (III) ion. Substitutions have been made to
      the host to optimise the host-guest association. Molecular mechanics calculations
      have been performed, using the UFF force field for metals, to decide on the
      suitability of the substitutions, and to evaluate the host-guest energies of
      association. Interesting general conclusions have been obtained, concerning the
      improvement of Magnetic Resonance Imaging contrast agents; namely, a set of
      rational methodologies have been deduced to improve the association between the
      gadolinium (III) chelates and the cyclodextrins, and their efficiency is
      demonstrated with a large set of substituted complexes, opening new doors to
      increase the diagnostic capabilities of Magnetic Resonance Imaging.

PMID- 14677641
TI  - Formation of multiple complexes between beta-dystroglycan and dystrophin family
      products.
AB  - Beta-dystroglycan is expressed in a wide variety of tissues and has generally
      been reported with an Mr of 43 kDa, sometimes accompanied with a 31 kDa protein
      assumed to be a truncated product. This molecule was recently identified as the
      anomalous beta-dystroglycan expressed in various carcinoma cell lines. We
      produced and characterized a G5 polyclonal antibody specific to beta-dystroglycan
      that is directed against the C-terminal portion of the molecule. We provide
      evidence that beta-dystroglycan may vary in size and properties by studying
      different Xenopus tissues. Besides normal beta-dystroglycan with an Mr of 43 kDa
      in smooth and cardiac muscle and sciatic nerve extracts, we found it in skeletal
      muscle and brain proteins with an Mr of 38 and 65 kDa, respectively.
      Glycosylation properties and proteolytic susceptibilities of these different beta
      dystroglycans are analysed and compared in this work. Crosslinking experiments
      with various beta-dystroglycan preparations obtained from skeletal and cardiac
      muscles and brain gave rise to specific new covalent products with Mr of 125 kDa
      (doublet band), or 120 and 130 kDa, or 140 and 240 kDa, respectively. We provide
      evidence, using various similar beta-dystroglycan preparations, that the
      immunoprecipitation procedure with G5 specific polyclonal antibody allows
      consistent pelleting of various dystrophin-family isoforms. Skeletal muscles from
      Xenopus reveals the presence of two distinct beta-dystroglycan complexes, one
      with dystrophin and another one which involves alpha-dystrobrevin. Cardiac muscle
      and brain from Xenopus are shown to contain three beta-dystroglycan complexes
      related to various dystrophin-family isoforms. Dystrophin or alpha-dystrobrevin
      or Dp71 were found in cardiac muscle and dystrophin or Dp180 or Up71 in brain.
      This variability in the relationship between beta-dystroglycan and dystrophin
      family isoforms suggests that each protein--currently known as dystrophin
      associated protein--could not be present in each of these complexes.

PMID- 14677642
TI  - Ectopic expression of an embryonic skeletal myosin heavy chain in human fetal and
      Syrian hamster hearts.
AB  - The mammalian heart is known to contain only two isoformic myosin heavy chain
      (MHC) genes, alpha and beta. A previously uncharacterized MHC gene was isolated
      in Syrian hamster hearts (McCully et al., JMol Biol 1991). We identified the
      novel MHC gene as a hamster embryonic skeletal MHC gene based on the
      developmental stage- and tissue-specific expression pattern: the restricted
      expression ofmRNA to striated muscles was highest in embryonic skeletal muscle
      and was developmentally down-regulated. We confirmed that the embryonic skeletal
      MHC gene exhibited higher expression in cardiomyopathic than in normal hamster
      hearts, and was up-regulated during the development of cardiomyopathy. The
      sporadic expression was highly localized in the endocardium. The present study
      identified that a very small number of undifferentiated myogenic cells existed in
      adult hamster endocardium. Moreover, using RT-PCR, a homologue of embryonic
      skeletal MHC mRNA was also expressed in human embryonic, but not adult
      ventricles. Our data provide a new insight into the regulatory mechanisms of MHCs
      in the cardiomyopathic hamster heart.

PMID- 14677643
TI  - The effect of extracellular tonicity on the anatomy of triad complexes in
      amphibian skeletal muscle.
AB  - Ultrastructural features of tubular-sarcoplasmic (T-SR) triad junctions and
      measures of cell volume following graded increases of extracellular tonicity were
      compared under physiological conditions recently shown to produce spontaneous
      release of intracellularly stored Ca2+ in fully polarized amphibian skeletal
      muscle fibres. The fibres were fixed using solutions of equivalent tonicities
      prior to processing for electron microscopy. The resulting anatomical sections
      demonstrated a partially reversible cell shrinkage corresponding to substantial
      increases in intracellular solute or ionic strength graded with extracellular
      tonicity. Serial thin sections through triad structures confirmed the presence of
      geometrically close but anatomically isolated transverse (T-) tubular and
      sarcoplasmic reticular (SR) membranes contrary to earlier suggestions for the
      development of luminal continuities between these structures in hypertonic
      solutions. They also quantitatively demonstrated accompanying decreases in T-SR
      distances, increased numbers of sections that showed closely apposed T and SR
      membranes, tubular luminal swelling and reductions in luminal volume of the
      junctional SR, all correlated with the imposed increases in extracellular
      osmolarity. Fully polarized fibres correspondingly showed elementary Ca(2+)
      release events ('sparks', in 100 mM-sucrose-Ringer solution), sustained Ca2+
      elevations and propagated Ca2+ waves (> or = 350-500 mM sucrose) following
      exposure to physiological Ringer solutions of successively greater tonicities.
      These were absent in hypotonic, isotonic or less strongly hypertonic
      (approximately 50 mM sucrose-Ringer) solutions. Yet exposure to hypotonic
      solutions also disrupted T-SR junctional anatomy. It increased the tubular
      diameters and T-SR distances and reduced their area of potential contact. The
      spontaneous release of intracellularly stored Ca2+ thus appears more closely to
      correlate with the expected changes in intracellular solute strength or a
      reduction in absolute T-SR distance rather than disruption of an optimal
      anatomical relationship between T and SR membranes taking place with either
      increases or decreases in extracellular tonicity.

PMID- 14677644
TI  - Ultrastructure of mouse striated muscle fibers following pravastatin
      administration.
AB  - To examine the effect of pravastatin administration on striated muscle
      ultrastructure, 10 BalbC mice were given pravastatin 40 mg/kg/day for 3 weeks. At
      the end of the study, blood was withdrawn for evaluation of the serum creatine
      phospho-kinase (CPK) level and the muscles of the hind legs, as well as the heart
      and liver of the animals were examined with a light and transmission electron
      microscope. After treatment with pravastatin the results showed a 101% increase
      in serum CPK level in comparison to untreated controls. Hematoxillin-eosin
      stained tissues of pravastatin treated mice did not show any abnormal findings.
      While the ultrastructure of the heart and liver of the treated animals appeared
      normal, the muscle fibers showed a marked alterations of the mitochondria, which
      were increased in size compared to those of the controls. The cristae were
      heavily damaged and even completely destructed, giving the mitochondria
      appearance of empty vacuoles. The findings are in favor of a specificity of
      pravastatin for striated muscles.

PMID- 14677645
TI  - Recovery of contractile and metabolic phenotypes in regenerating slow muscle
      after notexin-induced or crush injury.
AB  - The recovery of metabolic pathways after muscle damage has been poorly studied.
      We investigated the myosin heavy chain (MHC) isoform transitions and the recovery
      of citrate synthase (CS) activity, isoform distribution of lactate dehydrogenase
      (LDH) and creatine kinase (CK) in slow muscles after two types of injury. Muscle
      degeneration was induced in left soleus muscles of male Wistar rats by either
      notexin injection or crushing and the regenerative process was examined from 2 to
      56 days after injury. Myosin transition occurred earlier after notexin than after
      crush injury. Fast-type IIx and more particularly type IIa MHC isoform
      disappeared by day 28 after notexin inoculation, while they were still detected
      long after in crushed muscles. A full recovery of both the CS activity and the
      specific activity of the H-LDH subunit was observed from day 42 in notexin
      treated muscles, while values measured in crushed muscles remained significantly
      lower than in non-injured muscles (P < 0.05). The activity of the mitochondrial
      isoform of CK (mi-CK) was markedly affected by the type of injury (P < 0.001),
      and failed to reach normal levels after crush injury (P < 0.05). The results of
      this study show that the relatively rapid MHC transitions during regeneration
      contrasts with the slow recovery in the oxidative capacity. The recovery of the
      oxidative capacity remained incomplete after crush injury, a model of injury
      known to lead to disruption of the basal lamina and severe interruption of the
      vascular and nerve supply.

PMID- 14677646
TI  - The entire cDNA sequences of projectin isoforms of crayfish claw closer and
      flexor muscles and their localization.
AB  - Projectin is a giant protein related to twitchin and titin/connectin, that is
      found in arthropod striated muscle. The complete sequence of a 1 MDa projectin
      from Drosophila muscle was recently deduced from a thorough analysis of the
      genomic DNA (Southgate and Ayme-Southgate, 2001). Here we report the complete
      sequence for projectin from crayfish claw closer muscle (8625 residues; 962,634
      Da). The N-terminal sequence contains 12 unique 19-residue repeats rich in
      glutamic acid (E) and lysine (K). This region, termed the EK region, is clearly
      distinguishable from the PEVK-like domain of Drosophila projectin. The sequence
      of crayfish flexor projectin differs from that of closer muscle projectin in that
      there is a 114-residue deletion and a 35-residue insertion in the N-terminal
      region. Immunofluorescence microscopy demonstrated that projectin is mainly
      localized within the sarcomeric A band in both closer and flexor muscles,
      although the N-terminal region was shown to extrude into the I band region. In
      the closer muscles, invertebrate connectin (D-titin) connects the Z line to the
      edge of the A band (Fukuzawa et al., 2001). We have shown that invertebrate
      connectin is also present in flexor muscle sarcomeres, although in very low
      abundance.

PMID- 14677647
TI  - Plasticity of the transverse tubules following denervation and subsequent
      reinnervation in rat slow and fast muscle fibres.
AB  - We have studied the effects of short term denervation followed by reinnervation
      on the ultrastructure of the membrane systems and on the content of and
      distribution of key proteins involved in calcium regulation of fast-twitch (FT)
      extensor digitorum longus (EDL) and slow-twitch (ST) soleus (SOL) muscle fibres.
      Ischiadic nerve freezing resulted in total lack of neuromuscular transmission for
      3 days followed by a slow recovery, but no decline in twitch force elicited by
      direct stimulation. The latter measurements indicate no significant atrophy
      within this time frame. The membrane systems of skeletal muscle fibres were
      visualized using Ca92+)-K3Fe(CN)6-OsO4 techniques and observed using a high
      voltage electron microscope. [3H]nitrendipine binding was used to detect levels
      of dihydropyridine receptor (DHPR) expression. The Ca2+ pumping free sarcoplasmic
      reticulum domains were not affected by the denervation, but the Ca2+ release
      domains were dramatically increased, particularly in the FT-EDL muscle fibres.
      The increase is evidenced by a doubling up of the areas of contacts between SR
      and transverse (t-) tubules, so that in place of the normal triadic arrangement,
      pentadic and heptadic junctions, formed by multiple interacting layers of ST and
      t-tubules are seen. Frequency of pentads and heptads increases and declines in
      parallel to the denervation and reinnervation but with a delay. Immunofluorecence
      and electron microscopy observations show presence of DHPR and ryanodine receptor
      clusters at pentads and heptads junctions. A significant (P < 0.01) positive
      correlation between the level of [3H]nitrendipine binding component and the
      frequency pentads and heptads was observed in both the FT-EDL and ST-SOL muscle
      fibres indicating that overexpression of DHPRs accompanies the build up extra
      junctional contacts. The results indicate that denervation reversibly affects the
      domains of the membrane systems involved in excitation-contraction coupling.

PMID- 14677648
TI  - Lower active force generation and improved fatigue resistance in skeletal muscle
      from desmin deficient mice.
AB  - The mechanical effects of the intermediate filament protein desmin was examined
      in desmin deficient mice (Des-/-) and their wild type control (Des+/+). Active
      force generation was determined in intact soleus muscles and in skinned single
      fibres from soleus and psoas. A decreased force generation of skinned muscle
      fibres from Des-/- mice and a tendency towards decreased active force in intact
      soleus muscle were detected. Concentrations of the contractile protein actin and
      myosin were not altered in Des-/- muscles. Ca(2+)-sensitivity of skinned single
      fibres in Des-/- muscles was unchanged compared to Des+/+. Using a protocol with
      repeated short tetani an increased fatigue resistance was found in the intact
      soleus muscles from Des-/- mice. In conclusion, desmin intermediate filaments are
      required for optimal generation or transmission of active force in skeletal
      muscle. Although other studies have shown that the desmin intermediate filaments
      appear to influence Ca(2+)-handling, the Ca(2+)-sensitivity of the contractile
      filaments is not altered in skeletal muscle of Des-/- mice. Previous studies have
      reported a switch towards slower myosin isoforms in slow skeletal muscle of Des-/
      mice. The increased fatigue resistance show that this change is reflected in the
      physiological function of the muscle.

PMID- 14677649
TI  - Effects of glycine and proline on the calcium activation properties of skinned
      muscle fibre segments from crayfish and rat.
AB  - The effects of the polar amino acid glycine (20 mmol l(-1)) and the non-polar
      amino acid proline (20 mmol l(-1)) on Ca(2+)-activated contraction have been
      examined in four types of striated muscle fibres. Single fibres dissected from
      the claw muscle of a crustacean (long- and short-sarcomere) and the hindlimb
      muscles of the rat (slow-twitch from soleus and fast-twitch from extensor
      digitorum longus) were activated in matched solutions that either contained the
      amino acid ('test') or not ('control'). The steady-state force produced in these
      solutions was used to determine the relation between force production and pCa (
      log10[Ca2+]). The results show that in the concentrations used, glycine and
      proline had only small effects on the maximum Ca(2+)-activated force, pCa
      corresponding to 10, 50 and 90% maximum force (pCa10, pCa50, pCa90, respectively)
      or on the slope of the force-pCa curves in the four different fibre types. The
      relative lack of effects of glycine and proline on contractile activation would
      confer a distinct physiological advantage to force production of muscle of
      Cherax, where the concentrations of glycine and proline vary considerably.
      Finally, the results show that glycine and proline may be useful to balance
      control solutions when the effects of other amino acids or zwitterions on
      contractile activation are examined.

PMID- 14677650
TI  - Therapeutic clenbuterol treatment does not alter Ca2+ sensitivity of
      permeabilized fast muscle fibres from exercise trained or untrained horses.
AB  - Clenbuterol is a beta2-adrenoceptor agonist primarily used for treating
      bronchospasm and alleviating the symptoms of chronic obstructive pulmonary
      disease (COPD) in the horse. In other species (rats, mice, sheep, and cattle),
      chronic high doses of clenbuterol (typically in the milligram per kilogram body
      weight range) has been shown to cause a muscle directed protein anabolic
      response. Clenbuterol can also modify muscle fibre composition and therefore
      potentially affect muscle function. This has implications for the performance of
      exercising horses being treated with therapeutic doses of clenbuterol (typically
      in the microgram per kilogram body weight range) for bronchospasm or COPD. It is
      not known whether clenbuterol treatment affects muscle fibre function in horses.
      The purpose of this study was to examine the effects of a therapeutic dose of
      clenbuterol, with and without exercise, on the contractile activation
      characteristics of single membrane permeabilized fibres prepared from muscle
      biopsies. We tested the hypothesis that therapeutic treatment with clenbuterol
      would not affect muscle fibre function. Unfit Standardbred mares were treated for
      8 weeks with; clenbuterol (2.4 microg/kg twice/day, 5 days/week) plus exercise
      (20 min at 50% VO2(max) 3 d/wk; CLENEX), clenbuterol only (CLEN), or exercise
      only (EX). Muscle biopsies were taken from the gluteus medius muscle before and
      after treatment and stored in a glycerol-based solution to prepare permeabilized
      muscle fibres. The force-pCa relationship for fibres from CLEN horses was steeper
      (P < 0.05) indicative of greater cooperative interactions within the thin
      filament, however, fibre sensitivity to Ca2+ was unchanged. In contrast, the
      steepness of the force-pCa relationship was not changed in fibres from EX and
      CLENEX horses and Ca2+ sensitivity was also unaffected. Rigor force, activation
      in the absence of ATP, was not affected by any treatment indicating an
      approximately equivalent number of participating cross-bridges during activation.
      The results indicate that a therapeutic dose of clenbuterol to Standardbred
      horses does not affect the Ca(2+)-activated contractile characteristics of
      isolated muscle fibres.

PMID- 14677651
TI  - Mechanical responses of single non-confluent epithelial cells to low
      extracellular calcium.
AB  - Single non-confluent MDCK cells respond immediately to a sharp decrease in
      extracellular Ca2+ (< or = 5 microM) with an intense reversible retraction, along
      with an increase in cell height, correlating in overall rate and extent with
      initial cell size. Optical sectioning of individual cells by confocal microscopy
      showed that this structural response, observed in about 50% of the population,
      involves narrowing and even furrowing near the base of the cell by a thickened
      peripheral belt of actin filaments, which remains associated with the cortex
      instead of being internalized in the cytoplasm. Single cells retracted
      significantly in response to low Ca2+ under conditions that have been found
      largely inhibitory for retraction of confluent cells, such as Ca2+ replacement
      with Ba2+ and the substitution of Na+ with choline, a non-permeant cation.
      Conversely, the Na(+)-ionophore monensin applied in the normal-Ca2+ medium
      elicited by itself an earlier and much greater retraction in single cells than in
      confluent cultures. These observations indicate that single cells can retract
      more readily than those forming confluent cultures, suggesting that retraction in
      typical monolayers is resisted in part by the cell junctions. According to this
      view, inward actin-myosin mediated tension around the periphery of individual
      cells precedes and probably helps dissociation of E-cadherins in confluent
      cultures exposed to low Ca2+.

PMID- 14677652
TI  - Tissue immunoassay for 19F-tagged 5-hydroxytryptophan.
AB  - A new tool for magnetic resonance, L-6-heptafluorobutyryl-5-hydroxytryptophan,
      was synthesized and investigated using an antibody to perfluoroalkyl moieties
      developed previously. To be useful as an imaging agent, the compound must cross
      the blood brain barrier and then be concentrated in vesicles in serotonergic
      neurons in order to accumulate in sufficient quantity for in vivo detection to be
      possible. The novel imaging compound was administered in ova to domestic chicks
      (Gallus domestics) to investigate the bioavailability and uptake dynamics of the
      compound in this model organism. Typical immunoassay methods were ineffective, so
      a new technique was developed which binds amines and amino acids to the walls of
      acid-functionalized cuvettes. The first study established the presence of higher
      quantities of the tags in neural and liver tissue than in heart tissue. A second
      study investigated regional differences, with the midbrain containing more tagged
      compounds than the frontal lobe sample, and the frontal lobe sample containing
      more than the occipital or cerebellum samples. These studies demonstrate that the
      compound follows the pathway of endogenous serotonin. A third study investigated
      uptake dynamics of the novel compound. Maximum concentration of the tagged
      molecule in the brain was achieved three days after injecting Incubation Day 14
      eggs, suggesting that it bioaccumulates in vivo. This new immunoassay technique
      used to detect the novel compound in tissue samples demonstrated good
      repeatability.

PMID- 14677653
TI  - A time-resolved fluorescence immunoassay (DELFIA) increases the sensitivity of
      antigen-driven cytokine detection.
AB  - In an effort to improve the quantification of the low levels of cytokines
      released in response to antigenic stimulation of T cells, a sandwich dissociation
      enhanced lanthanide fluoroimmunoassay (DELFIA) was developed and compared to a
      standard sandwich ELISA. The DELFIA enhanced the sensitivity of a mouse IL-2
      assay 8- to 27-fold, and a human GM-CSF assay 10-fold, as compared to
      colorimetric ELISA. The increase in sensitivity allows for the use of lower
      sample volumes per well, and the ability to run more assays per supernatant
      sample. This sensitive, nonisotopic alternative to other cytokine detection
      methods will be useful for those researchers wanting to quantitate low levels of
      antigen-driven cytokine production.

PMID- 14677654
TI  - Normal value of immunoglobulins IgA, IgG, and IgM in Iranian healthy adults,
      measured by nephelometry.
AB  - Local reference ranges of immunoglobulins are required for studies and clinical
      interpretation. In this study, serum levels of IgA, IgG, and IgM in 914 Iranian
      healthy adult blood donor volunteers, aged 18-55 years, were measured by
      nephelometry. Our data showed that serum reference intervals of IgA, IgG, and IgM
      in subjects were 72-375, 636-1518, and 39-283 mg/dL, respectively. Data analysis
      showed a significant difference between the male and female subjects only for
      IgM; thus, the means of IgM in females were higher than for males (p < 0.05).
      Correlation coefficient r for paired samples showed no statistically significant
      relationship between age and each Ig (p > 0.05). Comparison of this study with
      others demonstrated that results are similar; some differences are probably
      related to ethnic differences. Therefore, our results can be considered as a
      source of reliable local reference for use in laboratories.

PMID- 14677655
TI  - Sensitive ELISA for determination of serum E2 using a new tracer E2-Biotin.
AB  - A new tracer conjugate of E2-Biotin, with different spacers, was synthesized at
      position 3 in the estradiol molecule for first time. Immunoreactivity of the
      tracer was determined by reacting with the anti-E2 monoclonal antibody. The
      monoclonal antibodies raised against E2 were characterized for its use in ELISA
      detection systems of serum E2. The purified antibody has a high affinity and
      specificity for E2. The antibody and tracer were used for establishing a
      competitive ELISA for estradiol (E2). The experimental results showed that the
      dose-response curve of the assay covered a range of 33-20,000 pg/mL (n = 8). The
      detection limit is 28.3 pg/mL (S/N = 3). The intra- and inter-assay coefficients
      of variation for the assay of serum samples ranged from 5.7 to 13.2% and from 5.3
      to 10.6%, respectively. Precoated microtiter plates were dried at 4 degrees C and
      they were stable for up to 3 months.

PMID- 14677656
TI  - Potential of laser immunoassay for detection of HIV in human blood serum and
      urine.
AB  - The potential of Light Scattering Immunoassay (LIA) for detection of HIV in human
      blood serum has been explored by monitoring the agglutination of antigen coated
      polystyrene particles by dynamic light scattering. ELISA tested human sera having
      HIV, TB, Filaria along with normal sera have been analyzed using two specific
      synthetic peptide antigen (SP1, SP2) and one nonspecific peptide antigen (NSP).
      Few paired human sera and urine samples and nonspecific (of nonHIV diseases)
      urine samples have also been tested using the same antigens to check the
      possibility of replacement of sera by urine.

PMID- 14677657
TI  - A novel antigen detection immunoassay for field diagnosis of hepatitis C virus
      infection.
AB  - The limitations of dominant methods-based on the detection of anti-HCV antibodies
      or HCV viremia currently used for the diagnosis of HCV infection enhance efforts
      to have a rapid, simple, sensitive, and specific alternative diagnostic approach
      to detect viral antigens. A highly reactive IgG antibody was raised to HCV-NS4
      recombinant antigen. The produced antibody showed no cross-reactivity with the
      other HCV structural and nonstructural recombinant antigens (C1 + 2, C3 + 4,
      E2/NS1, NS3, NS5). The well established ELISA technique was adapted to detect the
      new target HCV-NS4 antigen in serum samples. Extremely high agreement was found
      between the results of ELISA and qualitative detection of HCV-RNA, using a RT-PCR
      test as a gold standard for the diagnosis of HCV infection. Based on these
      encouraging results, a novel enzyme immunoassay; dot-ELISA was developed for
      rapid (approximately 5 min) and simple qualitative detection of the target HCV
      antigen in serum. The developed method detected the HCV target antigen in 95% of
      serum samples from HCV infected individuals, with a specificity of 97% using sera
      of noninfected individuals in comparison with PCR test. The antigen detection
      method showed high predictive values of positive (99%) and negative (90%).
      Moreover, the dot-ELISA could detect the HCV target antigen in sera negative for
      anti-HCV Abs, but positive for HCV-RNA, and in sera of HCV infected individuals
      with low viremia, as well as those with high viremia, using quantitative RT-PCR.
      Accordingly, the developed highly sensitive and specific HCV antigen detection
      method could be applied for mass screening of HCV infection.

PMID- 14677658
TI  - Development and validation of a simple sensitive enzyme immunoassay (EIA) for GH
      determination in buffalo plasma.
AB  - A simple and highly sensitive enzymeimmunoassay (EIA) for GH determination in
      buffalo plasma on microtitreplates using biotin-streptavidin amplification system
      and the second antibody coating was developed. Biotin was coupled to GH and used
      to bridge between streptavidin-peroxidase and immobilized antiserum in
      competitive assay. The EIA was carried out directly in 100 microL buffalo plasma.
      The GH standards ranging from 0.05 ng/well/100 microL to 12.8 ng/well/100 microL
      were prepared in hormone free plasma collected from an aged (> 15 years) senile
      buffalo. The sensitivity of the EIA procedure was 50 pg/well GH. which
      corresponded to 0.50 ng/mL plasma; the 50% relative binding sensitivity was seen
      at 800 pg/well/100 microL. Plasma volumes for the EIA, viz., 25, 50, and 100
      microL did not influence the shape of standard curve, even though a slight drop
      in the OD450 was seen with higher plasma volumes. For the biological validation
      of the assay, 12 Murrah buffalo calves were used. Six of these were administered
      synthetic bovine growth hormone-releasing factor (10 microg/100 kg body weight,
      i.v., and the remaining six animals were administered sterile normal saline and
      kept as controls. Jugular blood samples were collected at -60, -45, -30, -15, 
      10, -5, 5, 10, 15, and 30 min and, thereafter, at an interval of 15 min using an
      indwelling jugular catheter, beginning 1 h prior to GRF injection up to 8 h post
      treatment. In all animals, a peak of GH was recorded within 5 to 20 min of GRF
      administration, which confirms the biological validation of the EIA. To confirm
      homogeneity of buffalo GH with bovine GH, a parallelism test was conducted
      between the buffer standard curve of bovine GH and GH measured from serial
      dilution of buffalo plasma containing a high level of endogenous growth hormone.

PMID- 14677659
TI  - Breastfeeding and returning to work in the physician's office.

PMID- 14677660
TI  - No data to show link between opioid abuse and heroin use.

PMID- 14677661
TI  - Does metformin improve clinical features of polycystic ovary syndrome?

PMID- 14677662
TI  - Common acute hand infections.
AB  - Hand infections can result in significant morbidity if not appropriately
      diagnosed and treated. Host factors, location, and circumstances of the infection
      are important guides to initial treatment strategies. Many hand infections
      improve with early splinting, elevation, appropriate antibiotics and, if an
      abscess is present, incision and drainage. Tetanus prophylaxis is indicated in
      patients who have at-risk infections. Paronychia, an infection of the epidermis
      bordering the nail, commonly is precipitated by localized trauma. Treatment
      consists of incision and drainage, warm-water soaks and, sometimes, oral
      antibiotics. A felon is an abscess of the distal pulp of the fingertip. An early
      felon may be amenable to elevation, oral antibiotics, and warm water or saline
      soaks. A more advanced felon requires incision and drainage. Herpetic whitlow is
      a painful infection caused by the herpes simplex virus. Early treatment with oral
      antiviral agents may hasten healing. Pyogenic flexor tenosynovitis and clenched
      fist injuries are more serious infections that often require surgical
      intervention. Pyogenic flexor tenosynovitis is an acute synovial space infection
      involving a flexor tendon sheath. Treatment consists of parenteral antibiotics
      and sheath irrigation. A clenched-fist injury usually is the result of an
      altercation and often involves injury to the extensor tendon, joint capsule, and
      bone. Wound exploration, copious irrigation, and appropriate antibiotics can
      prevent undesired outcomes.

PMID- 14677663
TI  - Diagnosis of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus is a multisystem inflammatory disease that is often
      difficult to diagnose. Before the diagnosis can be established, four of 11
      clinical and laboratory criteria must be met. Antinuclear antibody titer is the
      primary laboratory test used to diagnose systemic lupus erythematosus. Because of
      the low prevalence of the disease in primary care populations, the antinuclear
      antibody titer has a low predictive value in patients without typical clinical
      symptoms. Therefore, as specified by the American College of Rheumatology, this
      titer should be obtained only in patients with unexplained involvement of two or
      more organ systems. Patients with an antinuclear antibody titer of 1:40 and
      characteristic multiorgan system involvement can be diagnosed with systemic lupus
      erythematosus without additional testing; however, patients with an antibody
      titer of 1:40 who fail to meet full clinical criteria should undergo additional
      testing, including tests for antibody to double-stranded DNA antigen and antibody
      to Sm nuclear antigen. While an antinuclear antibody titer of less than 1:40
      usually rules out systemic lupus erythematosus, patients with persistent,
      characteristic multisystem involvement may be evaluated for possible antinuclear
      antibody-negative disease.

PMID- 14677664
TI  - Amiodarone: guidelines for use and monitoring.
AB  - Amiodarone is a potent antiarrhythmic agent that is used to treat ventricular
      arrhythmias and atrial fibrillation. The drug prevents the recurrence of life
      threatening ventricular arrhythmias and produces a modest reduction of sudden
      deaths in high-risk patients. Amiodarone is more effective than sotalol or
      propafenone in preventing recurrent atrial fibrillation in patients for whom a
      rhythm-control strategy is chosen. When long-term amiodarone therapy is used,
      potential drug toxicity and interactions must be considered. The dosage of
      amiodarone should be kept at the lowest effective level. In patients who also are
      taking digoxin and warfarin, physicians must pay close attention to digoxin
      levels and prothrombin time, keeping in mind that the effects of interaction with
      amiodarone do not peak until seven weeks after the initiation of concomitant
      therapy. Laboratory studies to assess liver and thyroid function should be
      performed at least every six months.

PMID- 14677665
TI  - Returning to work while breastfeeding.
AB  - Mothers who work outside the home initiate breastfeeding at the same rate as
      mothers who stay at home. However, the breastfeeding continuance rate declines
      sharply in mothers who return to work. While the work environment may be less
      than ideal for the breastfeeding mother, obstacles can be overcome. Available
      breast pump types include manual pumps, battery-powered pumps, electric diaphragm
      pumps, electric piston pumps, and hospital-grade electric piston pumps. Electric
      piston pumps may be the most suitable type for mothers who work outside the home
      for more than 20 hours per week; however, when a mother is highly motivated, any
      pump type can be successful in any situation. Conservative estimates suggest that
      breast milk can be stored at room temperature for eight hours, refrigerated for
      up to eight days, and frozen for many months. A breastfeeding plan can help the
      working mother anticipate logistic problems and devise a practical pumping
      schedule. A mother's milk production usually is well established by the time her
      infant is four weeks old; it is best to delay a return to work until at least
      that time, and longer if possible.

PMID- 14677666
TI  - Information from your family doctor. Returning to work while breastfeeding.

PMID- 14677667
TI  - Approach to the adult patient with fever of unknown origin.
AB  - Fever of unknown origin (FUO) in adults is defined as a temperature higher than
      38.3 degrees C (100.9 degrees F) that lasts for more than three weeks with no
      obvious source despite appropriate investigation. The four categories of
      potential etiology of FUO are classic, nosocomial, immune deficient, and human
      immunodeficiency virus-related. The four subgroups of the differential diagnosis
      of FUO are infections, malignancies, autoimmune conditions, and miscellaneous. A
      thorough history, physical examination, and standard laboratory testing remain
      the basis of the initial evaluation of the patient with FUO. Newer diagnostic
      modalities, including updated serology, viral cultures, computed tomography, and
      magnetic resonance imaging, have important roles in the assessment of these
      patients.

PMID- 14677669
TI  - Escitalopram (Lexapro) for depression.
AB  - Escitalopram (Lexapro) is the active s-enantiomer of the selective serotonin
      reuptake inhibitor (SSRI), citalopram (Celexa). It is labeled for the treatment
      of major depressive disorder.

PMID- 14677670
TI  - Linear lesions on the face.

PMID- 14677671
TI  - ACIP releases recommendations for use of live, attenuated influenza vaccine.

PMID- 14677672
TI  - The OIE role in control of List A and emerging diseases.

PMID- 14677673
TI  - A survey of vaccines produced for OIE list A diseases in OIE member countries.
AB  - A survey was conducted to determine the availability, country of origin, and
      manufacturer of vaccines for all Office International Des Epizooties (OIE) list A
      diseases. A large number of classical swine fever, foot-and-mouth disease and
      Newcastle disease vaccines were found. A limited number of vaccines was also
      located for African horse sickness, bluetongue, contagious bovine
      pleuropneumonia, highly pathogenic avian influenza, lumpy skin disease, peste des
      petits ruminants, rift valley fever, rinderpest, sheep and goat pox, and
      vesicular stomatitis. No African swine fever or swine vesicular disease vaccines
      were found. Experimental vaccines are not included in this survey.

PMID- 14677674
TI  - International standards for vaccines for List A diseases.

PMID- 14677675
TI  - Regulatory considerations for emergency use of non-USDA licensed vaccines in the
      United States.
AB  - The Virus-Serum-Toxin Act of 1913 (21 US Code 151-159) provides the legal basis
      for the regulation of veterinary biologicals in the United States; the United
      States Department of Agriculture's Center for Veterinary Biologicals (CVB) has
      the regulatory authority for the issue of licences and permits for such products.
      The law was intended to establish standards and control the importation of
      products into the United States and the distribution of products interstate
      assuring the purity, safety, potency, and efficacy of veterinary biological
      products. Administrative regulations and standards appear in the Title 9, Code of
      Federal Regulations, Parts 101-118, with additional programme guidance found in
      CVB Notices, Veterinary Services Memoranda, General Licensing Considerations, and
      other guidance documents. Pre-licensing data evaluation procedures are designed
      to assess the purity, safety, potency, and effectiveness of each product and
      support all product label claims. To fulfil these criteria, data from all phases
      of product development are evaluated against these key elements. Under the
      standard licensing process, this spectrum of evaluation includes complete
      characterization and identification of seed material and ingredients, laboratory
      and host animal safety and efficacy studies, stability studies, and post
      licensing monitoring of field performance. This comprehensive evaluation may not
      be possible during the emergence of a new animal disease. While there are no
      specific regulations addressing the licensing standards of products for an
      emerging animal disease, there are mechanisms that allow for the availability of
      products in an emergency animal health situation. These mechanisms include
      autogenous biologicals, conditional licences, experimental and emergency use
      authorizations, and the importation of products in use elsewhere in the world.
      Pre-approved vaccine banks provide an additional mechanism.

PMID- 14677676
TI  - Regulatory considerations for emergency use of vaccines in the European Union.
AB  - From a regulatory perspective foot-and-mouth disease (FMD) vaccines represent a
      special case due to the number and antigenic diversity of strains that might be
      used alone or in combination within the context of an authorisation. New
      guidelines have been developed proposing that an FMD vaccine should be defined as
      a formulation of ingredients including defined amounts of one or more antigens
      that vary only in the number and types of antigen present. These new guidelines
      are in line with those previously proposed for equine influenza vaccines.
      Slaughter policies being less and less popular in the European Union, there is a
      tendency to use so-called marker vaccines associated with a companion diagnostic
      test. Such methodology has already been used for vaccination against pseudo
      rabies and infectious bovine rhinotracheitis. Sub-unit marker vaccines against
      classical swine fever have also been developed; such vaccines are also envisaged
      against foot-and-mouth disease; it would permit, if satisfying defined criteria,
      to distinguish vaccinated from infected animals.

PMID- 14677677
TI  - Vaccines and companion diagnostic tests for foot-and-mouth disease virus. An
      overview of the experience in South America.
AB  - Vaccination constitutes an important control policy for foot-and-mouth disease
      (FMD) in affected areas with advanced eradication programmes, as well as in free
      regions that decide to use immunization as a control measure after a recent
      introduction of the disease. However, considering that vaccinated animals exposed
      to FMD virus can establish sub-clinical infection and eventually remain
      persistently infected, availability of tools to identify sub-clinical infection
      and its silent transmission within and between herds, regardless of their
      vaccination state, is of utmost importance. In response to the need for new
      diagnostic tools to support the eradication campaigns implemented in 1988 in
      South America, during the past decade we have developed, validated and applied a
      highly sensitive and specific immuno-enzymatic system for recognition of
      persistence at a herd level. The system is based on the detection of antibodies
      against non-capsid proteins required for viral replication. These proteins, in
      principle, are removed from the viral suspensions destined for production of BEI
      inactivated vaccines. Within the validation steps, evaluation of potential
      induction of antibodies to non-capsid proteins caused by traces of these proteins
      eventually remaining in the vaccines was a major concern. This report presents a
      review on the experience gathered through the application of the system to
      various experimental and field immunization conditions. It was concluded that
      vaccination is not expected to induce antibody responses to non-capsid proteins
      that could lead to misinterpretation of serological investigations. Progress on
      the development of approaches towards vaccine certification to guarantee absence
      of interference will be discussed.

PMID- 14677678
TI  - Vaccines and foot-and-mouth disease eradication in South America.
AB  - Foot-and-mouth disease (FMD) vaccines have been a component of disease control
      and eradication strategies in South America ever since the first national
      programmes were created in the 1960s. By the mid 1970s, with the aid of
      international loans, FMD control programmes were implemented in almost every
      country and control measures strengthened. Livestock production forms are still a
      determining factor in the spread and prevalence of FMD and regional
      control/eradication strategies based on these forms were developed during the
      1980s, as part of the Hemispheric Plan for FMD Eradication, developed by
      Panaftosa-PAHO/WHO and the South American countries. The widespread use of oil
      adjuvant vaccines and the development of strategic schemes of coverage were
      instrumental in decreasing clinical disease and in controlling FMD to a point
      that eradication could be sought. This resulted in the recognition of countries
      and regions as free with and without vaccination Reappearance of FMD in
      Argentina, Southern Brazil and Uruguay were controlled with the aid of mass
      vaccination of bovines and other susceptible species, under special
      circumstances. Clinical FMD has been absent from Uruguay since August 2001; from
      Argentina since January 2002 and from Rio Grande do Sul, Brazil since July 2001.
      To prevent reintroduction of FMDV into free areas, national programmes must
      stress primary prevention activities with regional approaches and vaccination
      campaigns based on homogeneous coverage and timing, especially along
      international borders.

PMID- 14677679
TI  - Engineering better vaccines for foot-and-mouth disease.
AB  - Although efficacious and safe, current vaccines for FMD suffer from drawbacks.
      Among these are that the immune response to the vaccine interferes with the
      ability to detect vaccinated animals that have subsequently become infected and
      could carry and shed the virus, creating an obstacle to re-instating disease-free
      status to countries/regions that vaccinate to control outbreaks. Multiple
      diagnostic tests are available to identify animals that have been infected with
      FMDV by detection of antibodies to viral non-structural proteins (NSP) that are
      present in low concentration in traditional vaccines and are poorly immunogenic
      in vaccine preparations. However, these tests are not 100% reliable. To
      circumvent this problem, we have developed a new generation of vaccines that
      express the "empty capsid" subunit of the virus, in the absence of one of the
      most immunogenic NSPs, 3Dpol. Here we describe delivery of the empty capsid
      subunits by recombinant replication-defective human adenovirus type 5 (Ad5).
      These Ad5-vectored empty capsid vaccines can protect pigs from FMDV challenge as
      early as 7 days post-vaccination. A second problem with current FMD vaccines is
      that they do not induce protective immunity quickly, a drawback that is likely to
      be shared by our Ad5-vectored empty capsid vaccine. To overcome this problem, we
      have developed a prophylactic antiviral treatment consisting of an Ad5 encoding
      porcine interferon alpha (pIFNalpha). Administration of Ad5-pIFNalpha protects
      swine from FMD as early as one day post-administration. The combination of this
      antiviral treatment and the empty capsid subunit vaccine should induce rapid and
      complete protection from FMD, and could overcome current diagnostic problems.

PMID- 14677680
TI  - Development of new generation rinderpest vaccines.
AB  - Veterinary science has benefited much from the advances in biotechnology during
      the past 20 years. New and improved diagnostic techniques for infectious diseases
      have been developed and new and highly effective vaccines to prevent such
      diseases have been introduced and more have been, or are about to be, field
      tested. The latest development in negative strand virology, reverse genetics, the
      ability to rescue live virus from a DNA copy of the RNA genome, is being used to
      address questions concerning virus pathogenicity at the molecular level and to
      produce "marker" vaccines, i.e. vaccines that allow serological identification of
      all vaccinated animals. Such a vaccine would greatly benefit the continuing
      campaign for the global eradication of rinderpest since it would then be
      possible, by serological means, to detect wild type virus circulating in local
      areas or regions where it is still necessary to vaccinate and where the
      vaccination levels are below those required to eliminate the virus. Here we
      describe different approaches we have taken to produce such a vaccine using
      reverse genetics to add a marker to the existing and widely used Plowright
      rinderpest vaccine.

PMID- 14677681
TI  - Inexpensive vaccines and rapid diagnostic kits tailor-made for the global
      eradication of rinderpest, and technology transfer to Africa and Asia.
AB  - Rinderpest is an acute and highly contagious viral disease of ruminants, often
      resulting in greater than 90% mortality. We previously reported the development
      of first- and second-generation recombinant vaccinia virus vaccines which provide
      complete protection against rinderpest virus (RPV) and peste-des-petits ruminants
      virus (PPRV). These vaccines are safe even for immunodeficient mice and macaques
      with acquired immunodeficiency syndrome. We developed a third-generation
      recombinant vaccinia virus vaccine (v2RVFH) that expresses the fusion and
      haemagglutinin genes of RPV under strong synthetic vaccinia virus promoters.
      Cattle vaccinated intramuscularly with as little as 10(3) plaque-forming units
      (PFU) of v2RVFH were completely protected from rinderpest. Vaccinated animals did
      not develop pock lesions or transmit v2RVFH to contact animals. Cattle vaccinated
      with a standard dose of 10(8) PFU of v2RVFH developed long-term, sterilizing
      immunity against rinderpest. Thus, v2RVFH is safe, efficacious, heat stable,
      inexpensive, easily administered, and allows serological differentiation between
      vaccinated and infected animals. To aid in diagnosis and differentiation of
      vaccinated from infected animals, we developed indirect ELISAs (iELISAs) that use
      baculovirus-expressed RPV or PPRV nucleoprotein as coating antigens. A single
      larva contains enough viral antigen to test more than 10,000 serum samples, in
      duplicate. African scientists trained at the ILMB successfully transferred the
      iELISA kit technology to more than 30 countries in Africa, providing a model for
      technology transfer among developing countries. Vaccination with v2RVFH, in
      conjunction with the iELISA kits, greatly enhances the prospects for global
      eradication of rinderpest, as developing nations achieve independence in control
      efforts.

PMID- 14677682
TI  - Control of peste des petits ruminants: classical and new generation vaccines.
AB  - Peste des Petits Ruminants is a highly contagious disease of domestic and wild
      small ruminants. It seems to be the major constraint in the development of small
      ruminant production in areas where it is endemic. Included in the list A of the
      International Zoosanitary Code, it is also part of the FAO EMPRESS programme.
      Classically, it is characterised by fever, nasal and ocular discharges,
      diarrhoea, respiratory distress, mucosal erosive lesions and death in 40-80% of
      acute cases. All these clinical signs, apart from the respiratory symptoms, are
      very similar to those of rinderpest. The causal agents of both diseases are
      closely related and belong to the Morbillivirus genus. In the absence of
      homologous vaccine, and taking advantage of the close relationship between the
      two viruses, the attenuated tissue culture rinderpest vaccine has been used for a
      long time to protect small ruminants against PPR. At the end of 1980s, a PPRV
      strain was successfully attenuated by serial passages in Vero cells. Demonstrated
      to be very efficient in the protection of sheep and goats against a virulent
      challenge, this avirulent PPRV is now widely used in the control of PPR. Its
      thermostability has been dramatically improved by freeze drying. However, animals
      inoculated with this vaccine cannot be distinguished serologically from those
      infected with the wild type viruses. With the reverse genetics technique, it is
      now possible to engineer PPR marker vaccines which can allow such a
      differentiation. The genes of the PPRV immune protective proteins, the fusion and
      the haemagglutinin proteins, have been introduced into the genome of a capripox
      vaccine strain. The generated viruses have proved to be effective as a dual
      vaccine to protect against two major diseases of small ruminants: peste des
      petits ruminants and capripox infections.

PMID- 14677683
TI  - Development of improved attenuated and nucleic acid vaccines for heartwater.
AB  - Heartwater, an economically important tickborne disease of wild and domestic
      ruminants, is caused by the intracellular rickettsia Ehrlichia (formerly Cowdria)
      ruminantium. The only commercially available immunization procedure is more than
      50 years old and uses an infection and treatment regimen using a preparation of
      virulent organisms in cryopreserved sheep blood. Much research has been conducted
      into the development of attenuated, inactivated, and nucleic acid vaccines over
      the last half-century, with relatively little success until recently. We describe
      here the development of two new experimental vaccines, a live attenuated vaccine
      and a nucleic acid vaccine. The attenuation of virulent E. ruminantium was
      achieved by growing the organisms in a continuous canine macrophage-monocyte cell
      line. After more than 125 passages the cultures produced no disease when
      inoculated into mice or sheep, and the animals were completely protected against
      a subsequent lethal homologous needle challenge. The nucleic acid vaccine
      consists of a cocktail of four E. ruminantium genes, from a genetic locus
      involved in nutrient transport, cloned in a DNA vaccine vector. Sheep immunized
      with this cocktail were completely protected against a subsequent lethal needle
      challenge, either with the homologous isolate or with any one of five different
      virulent heterologous isolates. Protection against a field challenge in a
      heartwater endemic area, however, was relatively poor. Genetic characterization
      of the E. ruminantium genotypes in the challenge area did not identify any having
      major differences from those used in the heterologous needle challenge
      experiments, so lack of cross-immunity between the vaccine genotype and those in
      the field was unlikely to be the main reason for the lack of protection. We
      believe that a needle challenge is far less severe than a tick challenge, and
      that the immunity engendered by the DNA vaccine alone was not sufficient to
      protect against the natural route of infection. Boosting with live organisms
      after DNA vaccination results in much higher levels of protection against tick
      challenge than DNA vaccination alone, suggesting that improved methods of
      boosting could lead to more effective immunization.

PMID- 14677684
TI  - Development of improved vaccines for heartwater.
AB  - Heartwater is controlled by frequent application of acaricides, which is costly,
      creates endemic instability and has the potential of contaminating the
      environment. The live blood vaccine currently available has limitations because
      it is laborious and inconvenient to use, difficult to standardise and can
      transmit other blood-borne pathogens. The UF/USAID/SADC Heartwater Research
      Project has conducted research on the development of two types of vaccine for
      heartwater. The first-generation inactivated vaccine has been intensively tested
      in the laboratory and subsequently field tested in four southern African
      countries. It protects cattle, sheep and goats against mortality from heartwater
      challenge. It can be modified to incorporate any Ehrlichia ruminantium strain to
      provide protection from field challenge. The second-generation DNA vaccine
      containing genes encoding immunogenic E. ruminantium proteins has been developed
      and evaluated in the mouse model as well as in cattle and sheep. The use of
      improved vaccines against heartwater would have a positive impact on livestock
      farming in sub-Saharan Africa and the Caribbean and could be used to control the
      spread of heartwater if it were to be introduced into regions such as the United
      States.

PMID- 14677685
TI  - Contagious bovine pleuropneumonia vaccines, historic highlights, present
      situation and hopes.
AB  - Contagious bovine pleuropneumonia (CBPP) is a contagious infection of cattle
      caused by a mycoplasma, M. mycoides subsp. mycoides SC (MmmSC). It induces
      lesions of pleuropneumonia in acute cases and the formation of pulmonary
      "sequestra" in chronic cases. The disease is prevalent mostly in Africa, where it
      is responsible for high losses, but it has also been sporadically present in
      Southern Europe until 1999. Vaccination is now prohibited in most countries
      except in Africa. An empirical "inoculation" procedure was developed as early as
      1852 in Europe but it may have been used even earlier in Africa. The inoculation
      of pleural fluid was performed at the tip of the tail in Europe and on the bridge
      of the nose in Africa. It conferred good protection but induced a high number of
      fatal cases. Various inactivated preparations have been tested in the past with
      inconclusive results leading sometime to some protection and some other time to a
      sensitisation of the immunised animals. Such preparations have never been used in
      the field. Attenuated MmmSC strains have been developed in the 1950s and used
      extensively in the field both in Africa and Australia. The best known vaccine
      strains are KH3J, T1/44 and T1sr. Vaccination campaigns have succeeded in
      reducing considerably the CBPP prevalence in these two continents but eradication
      was achieved in Australia only by switching to strict measures of animal movement
      control and a stamping-out policy. The search for new CBPP vaccines has become a
      major issue for African countries that are facing an increase in outbreaks. The
      rationale for this search is based on a better understanding of the mycoplasma
      virulence mechanisms that could lead to a targeted attenuation of MmmSC strains.
      It is also based on a better understanding of the bovine immune response that may
      be driven to a pathogenic inflammatory response or conversely to a better
      balanced response leading to protection.

PMID- 14677686
TI  - Vaccines for lumpy skin disease, sheep pox and goat pox.
AB  - Sheep pox, goat pox and lumpy skin disease (Neethling) are diseases of sheep,
      goats and cattle respectively, caused by strains of poxvirus, within the genus
      Capripoxvirus. Strains affecting sheep and goats are not totally host-specific;
      some cause disease in both sheep and goats while others may cause disease in only
      one species. Those causing disease in cattle appear to be specific for cattle,
      and this is reflected in the different geographical distribution of lumpy skin
      disease (LSD) and sheep pox and goat pox (sheep and goat pox); LSD is confined to
      Africa, while sheep and goat pox are present in Africa north of the equator, and
      throughout West Asia and India, as far East as China and Bangladesh. Occasionally
      sheep and goat pox spreads from Turkey into Greece. All strains of capripoxvirus
      so far examined are antigenically indistinguishable, and recovery from infection
      with one strain provides immunity against all other strains. Because of this
      antigenic homology among all strains, there is the potential to use a single
      vaccine strain to protect cattle, sheep and goats.

PMID- 14677687
TI  - Nature and duration of protective immunity to bluetongue virus infection.
AB  - Genetic engineering offers a variety of approaches to producing viral vaccines.
      An exciting advance in this field is the ability to construct virus-like
      particles (VLPs) that resemble their natural counterparts but lack genetic
      information. To develop a rationally designed vaccine for bluetongue disease of
      sheep that is caused by virus (BTV), we have synthesised individual BTV proteins
      and BTV-like particles (VLPs and CLPs) using baculovirus expression systems and
      insect cell cultures. A series of clinical trials were undertaken using these
      proteins and particles in BTV-susceptible sheep. The accumulated data obtained
      from these studies are: (i) the two surface proteins when used in high doses
      (approximately 100 microg/dose) could afford complete protection in sheep against
      virulent virus challenge; (ii) in contrast, only 5-10 microg of VP2 of a related
      virus, African horse sickness virus (AHSV) afforded protection in horses against
      virulent virus challenges when vaccinated in the presence of appropriate
      adjuvant; (iii) vaccination with as little as 10 microg VLPs (consisting of all
      four major proteins) gave long lasting protection (at least for 14 months)
      against homologous BTV challenge; (iv) cross-protection was also achieved
      depending on the challenge virus and amounts of antigen used for vaccination and
      (v) limited vaccination trials with CLPs (containing only two highly conserved
      internal proteins) afforded partial (with slight fever) protection against
      homologous and heterologous virus challenges. Since CLPs are conserved across the
      twenty four BTV serotypes, CLPs could have potential for a candidate vaccine that
      may at least mitigate the disease and inhibit virus spread. In summary, VLPs and
      CLPs offer completely safe and efficacious vaccines as their particles are devoid
      of any detectable amount of insect, baculovirus proteins or nucleic acids and
      thus pose no potential adverse effects.

PMID- 14677688
TI  - Marker vaccines and companion diagnostic tests for classical swine fever.
AB  - For Classical Swine Fever (CSF) a subunit vaccine consisting of the E2 protein is
      commercially available. The discriminatory ELISAs detect antibodies against
      another viral protein, the E(rns). As CSF has already been eradicated from many
      countries the use of a marker vaccine in these regions can only be contemplated
      as emergency vaccination after a new introduction of virus. Therefore, a Large
      Scale Marker Vaccine Trial was financed by the EU Commission and organised by the
      EU Reference Laboratory for CSF in 1999. When tested under the conditions of
      emergency vaccination, e.g. challenge before full immunity had developed, it was
      shown, that most CSF challenge infections took a subclinical course with reduced
      virus shedding. Transplacental transmission in pregnant sows could not be
      prevented after an application of a single vaccine dose. The most serious
      deficiencies have been found in the discriminatory ELISAs. Both available tests
      have shown deficiencies in sensitivity and specificity compared to conventional
      CSF antibody ELISAs. At the time, when the trial was performed, no confirmatory
      test was available to verify the results of the discriminatory ELISAs. Currently
      two new developments of marker vaccines for CSF are in progress. A chimaeric
      vaccine is based on infectious clones of the conventional live vaccine (C-strain)
      where a gene is replaced with the corresponding gene of the closely related
      pestivirus Bovine Viral Diarrhoea (BVD) virus. Conversely, the E2 gene of a BVD
      virus can be replaced by the E2 of a virulent CSF virus. The other principle is
      the construction of a DNA vaccine, expressing the E2 gene after entering the host
      cell. Deletion mutants of the E2 gene have also been constructed and tested for
      their induction of immunity. Both new developments are based on the same
      discriminatory tests as mentioned previously and developments of other principles
      for discrimination are rare.

PMID- 14677689
TI  - Suitability of an E2 subunit vaccine of classical swine fever in combination with
      the E(rns)-marker-test for eradication through vaccination.
AB  - Vaccination with modified live vaccines (C-, GPE-minus strain) against Classical
      Swine Fever (CSF) is an efficient tool in its control. However, for monitoring
      infection in a vaccinated population, marker-vaccines are preferred. A review is
      given on the efficacy of the E2 marker-vaccine, Porcilis Pesti. Protection starts
      to come up at seven days pv. Reduction of horizontal virus transmission starts to
      show at 10 days pv, is almost complete at 14 days and complete at 21 days after a
      single vaccination. Single vaccination of pregnant sows hardly prevents vertical
      transmission. Double vaccination prevents horizontal transmission as measured by
      virus isolation from the contact pigs. Double vaccination of pregnant sows
      prevents vertical transmission in the majority of the piglets. Data on the second
      version of the accompanying test, Chekit-CSF-Marker, show in a negative
      population a specificity of 98.8%. In a set of reference sera the improved test
      compares well with the results of a VNT. In a challenge experiment all pigs
      seroconverted between 1 and 3 weeks after challenge.

PMID- 14677690
TI  - Vaccines for List A poultry diseases: emphasis on avian influenza.
AB  - Various vaccine technologies have been shown experimentally to be effective for
      immunization against avian influenza (AI) virus and include conventional
      inactivated oil-based whole AI virus, vectored virus, subunit protein and DNA
      vaccines. Vaccine-induced protection is based upon antibodies produced against
      the surface glycoproteins, principally the haemagglutinin, but also the
      neuraminidase. This protection is specific only for individual subtypes of
      haemagglutinin (H1-15) and neuraminidase (N1-9) proteins. AI vaccines protect
      chickens and turkeys from clinical signs and death, and reduce respiratory and
      intestinal replication of a challenge virus containing homologous haemagglutinin
      protein. Many of the vaccines are effective if given as a single injection and
      provide protection for greater than 20 weeks. Protection has been demonstrated
      against both low and high doses of challenge virus. Furthermore, subtype H5 AI
      vaccine has been shown to provide protection against heterologous H5 strains with
      89.4% or greater haemagglutinin deduced amino acid sequence similarity and
      isolated over 38 years. Currently, inactivated whole AI virus vaccines and a fowl
      pox-vectored vaccine with AI H5 haemagglutinin gene insert are used commercially
      in various countries of the world. These vaccines have some disadvantages
      associated with the labour requirements for parenteral administration. However,
      an experimental recombinant Newcastle disease virus vaccine with an AI
      haemagglutinin gene insert shows some promise as a low cost, mass administered
      aerosol vaccine. A critical issue for the use of vaccines in the field is the
      need to differentiate vaccinated birds from those infected with the field virus.
      Differentiation is necessary for outbreak surveillance and trade. The use of AI
      vaccines varies with individual countries and for different AI virus subtypes.

PMID- 14677691
TI  - Vaccination policy applied for the control of avian influenza in Italy.
AB  - This paper describes the measures applied to control the re-emergence of the low
      pathogenicity avian influenza virus of the H7N1 subtype which followed the
      devastating HPAI epidemic in Italy between 1999 and 2000. To control the LPAI
      virus and to develop a novel control strategy, a "DIVA" (Differentiating Infected
      from Vaccinated Animals) strategy was developed and combined to a strict
      territorial control programme. The "DIVA" strategy was based on the use of an
      inactivated oil emulsion vaccine containing the same haemagglutinin (H) sub-type
      as the field virus, but a different neuraminidase (N). The possibility of using
      the diverse N group, to differentiate between vaccinated and naturally infected
      birds, was achieved through the development of an "ad hoc" serological test based
      on the detection of specific anti-N1 antibodies. The control programme included
      an intensive sero-surveillance programme aiming at detecting the circulation of
      the LPAI virus, through the regular testing of vaccinated and unvaccinated flocks
      and the evaluation of the efficacy of the vaccination schemes in the field. The
      experience gained during the Italian 1999-2001 AI epidemic, suggests that the
      combination of a "DIVA" control strategy with a territorial monitoring system
      under official control can represent an effective tool for the control of avian
      influenza infections in poultry. In addition, the application of a "DIVA"
      vaccination policy, as opposed to a conventional policy enabled veterinary public
      health organisations to establish that infection was not circulating any longer,
      and ultimately resulted in the possibility of marketing meat obtained from
      animals vaccinated against an OIE List A disease.

PMID- 14677692
TI  - Equine vaccine for West Nile virus.
AB  - To meet the urgent need of controlling West Nile virus (WNV) infection in the
      equine population, we have developed a killed WNV vaccine. A dose titration study
      in horses was first conducted to evaluate serum neutralization antibody responses
      against WNV in these animals. Horses were vaccinated intramuscularly twice with
      the test vaccine at low, medium and high dose, three weeks apart. Serum samples
      were collected periodically and were measured for serum neutralizing antibody
      using a plaque reduction neutralization test. Significant increases in serum
      neutralizing antibody were detected in all three dosage groups 14 days post the
      second vaccination. Twelve months after the second vaccination, horses vaccinated
      with the medium dose of WNV vaccine and non-vaccinated control horses were
      experimentally challenged with WNV. Nine out of 11 (81.8%) controls developed
      viraemia after challenge while only one out of 19 (5.3%) vaccinates had transient
      viraemia, representing a 94% preventable fraction. In a separate study, the
      safety of the killed WNV vaccine was demonstrated under field conditions. A total
      of 648 horses, including 32 pregnant mares, were enrolled in the study. During
      the two weeks post vaccination period, no local or systemic adverse reactions
      were observed following 96% of the vaccinations administered while mild,
      transient injection site reactions were noted in a small number of horses. These
      results indicate that the killed WNV vaccine developed by Fort Dodge Animal
      Health is safe and efficacious.

PMID- 14677693
TI  - Suitability of currently available vaccines for controlling the major
      transboundary diseases that afflict sub-Saharan Africa.

PMID- 14677694
TI  - Challenges and opportunities in developing and marketing vaccines for OIE List A
      and emerging animal diseases.
AB  - Veterinary pharmaceutical products generated 14.5 billion U.S. Dollars (USD) in
      worldwide sales in 2000, with biological products contributing 16.2 percent or
      2.3 billion USD. The leading biological products were foot-and-mouth disease
      (FMD) vaccines, with 284 million USD in sales, representing 26.4 percent of the
      entire livestock biological business. Despite the potential opportunities for the
      biologicals industry, non-vaccination policies and undefined control and
      eradication strategies have deterred the private sector from significant
      investments in the research and development of vaccines against List A diseases.
      The primary research focus remains vaccines for infectious diseases that have an
      impact on current domestic herd health management systems. Changing the vaccine
      paradigm, investing in new technologies, and creating the future by integrating
      into key alliances with producers and regulatory authorities will be paramount in
      protecting our poultry and livestock industries against highly infectious
      diseases and potential acts of bioterrorism.

PMID- 14677695
TI  - New vaccines and their impact on programmes for controlling pig diseases.

PMID- 14677696
TI  - Emergency vaccination against classical swine fever.
AB  - At present, emergency vaccination against classical swine fever is not practised
      in Western countries. However, stamping out and pre-emptive culling policies are
      increasingly meeting greater resistance. Consequently, emergency vaccination is a
      re-emerging subject of debate. There are highly efficacious classical live
      vaccines that induce early immunity, but their use precludes the serological
      discrimination of infected and vaccinated pigs. Therefore, E2 subunit DIVA
      vaccines have been developed that allow this discrimination. However, their
      efficacy is lower than that of the live vaccines and the companion diagnostic
      differential test, the E(rns) ELISA, has its limitations. Modern biotechnological
      methods enabled researchers to develop a variety of candidate vaccines that have
      been shown to induce immunity in pigs. However, it is not expected that one of
      them will enter the marketplace in less than five to 10 years. The current
      vaccines should therefore be used, if emergency vaccination programmes to
      eradicate classical swine fever are to be implemented in the near future. Two
      possible scenarios for emergency vaccinations are discussed.

PMID- 14677697
TI  - Control and eradication of O.I.E. list A diseases--the approach of the European
      Union to the use of vaccines.
AB  - In the last decade the European Union has experienced serious outbreaks of
      certain O.I.E. list A diseases such as foot-and-mouth disease, classical swine
      fever and avian influenza. These diseases have been controlled and eradicated by
      means of culling and destroying a very large number of animals, which has been
      very expensive and has raised ethical questions. In accordance with existing
      rules, emergency vaccination has also been applied under certain circumstances,
      but its use has often been hampered by the impossibility of distinguishing
      vaccinated but healthy animals from the infected ones and by its negative impact
      on the trade of the vaccinated animals and their products. Marker vaccines and
      suitable accompanying discriminatory tests may overcome these problems and be
      used as additional eradication tools, where appropriate. Provisions on the use of
      these tools have already been introduced in the legislation of the European
      Union.

PMID- 14677698
TI  - Factors to consider when using vaccine to control an exotic disease outbreak.
AB  - Recent global events have dramatically increased the attention given to
      veterinary medical regulatory authorities' responsibility of protecting their
      country's agricultural interests from the threat of exotic disease outbreaks. A
      vaccine can be a valuable tool to help curb the spread of an exotic disease
      epidemic and/or lessen its economic impact. However, the decision on whether or
      not to use a vaccine during an outbreak may be complex and have far-reaching
      impacts. The decision must be approached in a logical and orderly fashion, taking
      into account the scientific, economic, political, and practical considerations
      that are unique to each individual disease outbreak. A decision-making process
      for the use of a vaccine developed for foot-and-mouth disease and its potential
      application to help decide on the use of vaccines in other exotic disease
      outbreaks is discussed.

PMID- 14677699
TI  - Phytase enzymology, applications, and biotechnology.
AB  - Phytases are phosphohydrolases that initiate the step-wise removal of phosphate
      from phytate. These enzymes have been widely used in animal feeding to improve
      phosphorus nutrition and to reduce phosphorus pollution of animal waste. The
      potential of phytases in improving human nutrition of essential trace minerals in
      plant-derived foods is being explored. This review covers the basic biochemistry
      and application of phytases, and emphasizes the emerging biotechnology used for
      developing new effective phytases with improved properties.

PMID- 14677700
TI  - On-line monitoring of the methanol concentration in Pichia pastoris cultures
      producing an heterologous lipase by sequential injection analysis.
AB  - An automated sequential injection analysis (SIA) system using stop-flow technique
      was developed to determine methanol concentration by means of the enzymatic
      reactions of alcohol oxidase and peroxidase. Its application as an on-line device
      for monitoring Pichia pastoris fermentations producing an heterologous protein
      was demonstrated. Linear response, observed up to 2 g l(-1), was reached by
      including a dilution chamber in the SIA manifold. The sampling frequency was 7
      analyses per hour with a relative standard deviation lower than 4%.

PMID- 14677701
TI  - Chromium (III) enhanced diamine silver staining of proteins and DNA in gels.
AB  - Chromium (III) enhanced the sensitivities of diamine silver staining of four
      proteins between 6- and 50-fold over that of the Coomassie Brilliant Blue (CBB)
      chromium modified thiosulfate-silver staining method (Zhou et al. Biotechnology
      Letters, 2002, 24: 1561-1567). Using six dsDNA fragments, the detection limits of
      this new method was 10 to 30 pg per band, being 10- to 25-fold more sensitive
      than previous methods.

PMID- 14677702
TI  - The silk protein, sericin, protects against cell death caused by acute serum
      deprivation in insect cell culture.
AB  - Sericin is the silk protein that covers fibroin fibers and functions as a 'glue'
      in the cocoons of silkworms, and its most abundant component, Ser1, contains
      repeats of Ser- and Thr-rich 38 amino acid residues. The viability of Sf9 insect
      cells was 20, 57 and 49% on the fifth day and 41, 91 and 70% on the ninth day
      after serum deprivation in the presence of no additives, 3000 microg sericin
      hydrolysate and 350 microg SerD (the peptide containing the two repetitive units)
      ml(-1), respectively. Thus, the sericin samples were useful in preventing cell
      death and promoting cellular growth after acute serum deprivation.

PMID- 14677703
TI  - Batch xylitol production from wheat straw hemicellulosic hydrolysate using
      Candida guilliermondii in a stirred tank reactor.
AB  - Batch production of xylitol from the hydrolysate of wheat straw hemicellulose
      using Candida guilliermondii was carried out in a stirred tank reactor (agitation
      speed of 300 rpm, aeration rate of 0.6 vvm and initial cell concentration of 0.5
      g l(-1)). After 54 h, xylitol production from 30.5 g xylose l(-1) reached 27.5 g
      l(-1), resulting in a xylose-to-xylitol bioconversion yield of 0.9 g g(-1) and a
      productivity of 0.5 g l(-1) h(-1).

PMID- 14677704
TI  - Decolorization of azo dyes by Rhodobacter sphaeroides.
AB  - Rhodobacter sphaeroides AS1.1737 decolorized more than 90% of several azo dyes
      (200 mg dyes l(-1)) in 24 h. The optimal culture conditions were: anaerobic
      illumination (1990 1x), peptone as carbon source, temperature 35-40 degrees C and
      pH 7-8. Intracellular crude enzyme from this strain had azoreductase activity,
      optimized temperature as 45-50 degrees C, and decolorization kinetics which were
      consistent with a ping-pong mechanism.

PMID- 14677705
TI  - A novel, repeated fed-batch, ethanol production system with extremely long term
      stability achieved by fully recycling fermented supernatants.
AB  - Using Saccharomyces cerevisiae, a novel, repeated fed-batch ethanol production
      system from corn flour by fully recycling fermented supernatants is demonstrated.
      With recovery of ethanol by evaporation coupled with consecutive removal of the
      insoluble and soluble inhibitory substances accumulated, either completely or
      partially by filtration, the concentrations of the soluble inhibitors in the
      system could be maintained at their equilibria. As a result, a sustained high
      concentration of ethanol (up to 15% v/v) and significant pollution control
      performance were obtained.

PMID- 14677706
TI  - Bioconversion of compactin into pravastatin by Streptomyces sp.
AB  - Streptomyces sp. Y-110, isolated from soil, modified compactin to pravastatin, a
      therapeutic agent for hypercholesterolemia. In a batch culture, the highest
      production of pravastatin was 340 mg l(-1) from 750 mg compactin l(-1) in 24 h.
      By intermittent feeding of compactin into the culture medium, both the compactin
      concentration and its conversion increased to 2000 mg l(-1) and 1000 mg
      pravastatin l(-1), respectively, with the conversion rate of 10 mg l(-1) h(-1).
      Continuous feeding of compactin increased production of pravastatin to 15 mg l(
      1) h(-1).

PMID- 14677707
TI  - Fed-batch fermentation of Lactobacillus lactis for hyper-production of L-lactic
      acid.
AB  - A fed-batch fermentation of Lactobacillus lactis to produce L-lactic acid was
      developed in which the residual glucose concentration in the culture was used to
      control a continuous feeding strategy. Up to 210 g L-lactic acid l(-1) (97%
      yield) was obtained. The maximal dry cell was 2.7 g l(-1) and the average L
      lactic acid productivity was 2 g l(-1) h(-1).

PMID- 14677708
TI  - Optimization of a fermentation medium using neural networks and genetic
      algorithms.
AB  - Artificial neural networks and genetic algorithms are used to model and optimize
      a fermentation medium for the production of the enzyme hydantoinase by
      Agrobacterium radiobacter. Experimental data reported in the literature were used
      to build two neural network models. The concentrations of four medium components
      served as inputs to the neural network models, and hydantoinase or cell
      concentration served as a single output of each model. Genetic algorithms were
      used to optimize the input space of the neural network models to find the optimum
      settings for maximum enzyme and cell production. Using this procedure, two
      artificial intelligence techniques have been effectively integrated to create a
      powerful tool for process modeling and optimization.

PMID- 14677709
TI  - Microbial synthesis of (R)- and (S)-3,4-dimethoxyamphetamines through
      stereoselective transamination.
AB  - Two soil isolates, Arthrobactersp. KNK168 and Pseudomonas sp. KNK425, aminated
      3,4-dimethoxyphenylacetone in presence of sec-butylamine as an amino donor to
      yield 3,4-dimethoxyamphetamine (DMA) with different enantioselectivities. The
      former gave (R)-DMA (>99% e.e.) and the latter the (S)-isomer (>99% e.e.).

PMID- 14677710
TI  - Construction of an amylolytic industrial strain of Saccharomyces cerevisiae
      containing the Schwanniomyces occidentalis alpha-amylase gene.
AB  - The gene encoding Schwanniomyces occidentalis alpha-amylase (AMY) was introduced
      into the chromosomal delta sequences of an industrial strain of Saccharomyces
      cerevisiae. To obtain a strain suitable for commercial use, an delta-integrative
      cassette devoid of bacterial DNA sequences was constructed that contains the AMY
      gene and aureobasidin A resistance gene (AUR1-C) as the selection marker. The AMY
      gene was expressed under the control of the alcohol dehydrogenase gene promoter
      (ADC1p). The alpha-amylase activity of Sacc. cerevisiae transformed with this
      integrative cassette was 6 times higher than that of Sch. occidentalis. The
      transformants (integrants) were mitotically stable after 100 generations in
      nonselective medium.

PMID- 14677711
TI  - Astragaloside IV and polysaccharide production by hairy roots of Astragalus
      membranaceus in bioreactors.
AB  - Hairy roots of Astragalus membranaceus were grown in bioreactors up to 30 l for
      20 d. Cultures from a 30 l airlift bioreactor gave 11.5 g l dry wt with 1.4 mg g(
      1) astragaloside IV, similar to cultures from 250 ml and 1 l flasks, but greater
      than yields from a 10 l bioreactor (dry wt 9.4 g l(-1), astragaloside IV 0.9 mg
      g(-1)). Polysaccharide yields were similar amongst the different bioreactors
      (range 25-32 mg g(-1)). The active constituent content of the cells approached
      that of plant extracts, indicating that large scale hairy root cultures of A.
      membranaceus has the potential to provide an alternative to plant crops without
      compromising yield or pharmacological potential.

PMID- 14677712
TI  - Application of solvent engineering to optimize lipase-catalyzed 1,3
      diglyacylcerols by mixture response surface methodology.
AB  - 1,3-Diacylglycerol (DAG) has been introduced in Japan as a cooking oil under the
      trade name of Econa to reduce body fat accumulation. Solvent engineering was
      applied to determine the optimum solvent mixtures for the lipase-catalyzed
      synthesis of 1,3-DAG by mixture response surface methodology. n-Hexane was
      required to maintain the lipase activity and the product selectivity could be
      adjusted by changing the hydrophobicity of reaction medium. The optimum yield
      (approximately 40%) of 1,3-DAG synthesis was obtained with n-hexane/octane (1:1,
      v/v).

PMID- 14677713
TI  - Stereochemistry of a diastereoisomeric amphiphile and the species of the lipase
      influence enzyme activity in the transesterification catalyzed by a lipase-co
      lyophilizate with the amphiphile in organic media.
AB  - Modified Candida rugosa and Pseudomonas cepacia lipase (CRL and PCL) were co
      lyophilized with two pairs of synthetic diastereoisomeric amphiphiles, D- and L-2
      (3-[bis-[3-(2,3,4,5,6-pentahydroxy-hexanoylamino)-propyl]-carbamoyl]
      propionylamino)-pentanedioic acid didodecyl ester (D- and L-BIG2C12CA); D- and L
      2-(2,3,4,5,6-pentahydroxy-hexanoylamino)-pentanedioic acid didodecyl ester (D-
      and L-2C12GE). Enzyme activities of the modified lipase in the
      transesterification in organic solvent were evaluated. Both pairs of the
      diastereoisomeric amphiphiles showed enhanced enzyme activity in the
      transacetylation between racemic sulcatol and isopropenyl acetate in diisopropyl
      ether, catalyzed by the PCL-co-lyophilizate, by 19-48 fold when compared to the
      native lipase lyophilized from buffer alone independent of the stereochemistry of
      the amphiphiles, while in the case of the CRL-co-lyophilizate only the L
      BIG2C12CA showed enhanced enzyme activity in the transbutyrylation between
      racemic solketal and vinyl butyrate in cyclohexane as high as 68-78 fold.

PMID- 14677715
TI  - Imatinib mesylate (STI 571)--a new oral target therapy for chronic myelogenous
      leukemia (CML).
AB  - The publication provides an up-to-date review of the significance of cytogenetic
      abnormalities in chronic myelogenous leukemia (CML) and the development of a
      promising agent with specific molecular target against tyrosine kinase, product
      of the BCR-ABL fusion gene, namely imatinib mesylate (STI 571, Glivec). The
      publication summarizes the achieved results with this compound in the chronic
      phase CML (in patients resistant to interferon and in newly diagnosed patients)
      further in patients in the accelerated phase and in blast crisis and in patients
      in relapse after allogeneic stem cells transplantations for CML. The results in
      Ph+ acute lymphoblastic leukemia are also presented. The mechanisms of resistance
      to imatinib mesylate and the possibilities how to overcome or circumvent it are
      mentioned (escalation of the dosage, combination of imatinib with some other
      treatment modalities as immunotherapy, interferon or convention chemotherapy and
      development of new drugs).

PMID- 14677714
TI  - Normalization of reverse transcription quantitative-PCR with housekeeping genes
      in rice.
AB  - Reverse transcription followed by real-time quantitative polymerase chain
      reaction (RT Q-PCR) is useful for the systematic measurement of plant
      physiological changes in gene expression. The validity of using 18S rRNA and
      three housekeeping genes, glyceraldehyde-3-phosphate dehydrogenase, actin, and
      tubulin, was tested as a reference of RT Q-PCR. Under various growth stages of
      etiolated seedlings, different cultivars, and various times after UV-irradiation
      treatment, expression level of 18S rRNA correlated with total RNA suggesting the
      uniformity of RT Q-PCR efficiencies among samples. Relative expressions of
      housekeeping genes varied among samples and independently of experimental
      conditions, up to two-fold, signifying generally constant fraction of mRNA in
      total RNA. Results indicate 18S rRNA was the most reliable reference gene for RT
      Q-PCR of total RNA.

PMID- 14677716
TI  - Early childhood caries.
AB  - Early childhood caries (ECC) represents a serious problem in pediatric dentistry.
      Not only because of its rapidity but also because of age of affected children.
      This has been given different names such as "rampant caries" and "baby bottle
      syndrome" but now all clinical manifestations have been joined and classified as
      early childhood caries. The topic of this article is the prevalence, etiology,
      clinical manifestations and preventive measures of ECC.

PMID- 14677717
TI  - The repair of DNA damage induced in human peripheral lymphocytes with styrene
      oxide.
AB  - Isolated human peripheral lymphocytes were treated in vitro with styrene-7, 8
      oxide (SO) and the kinetics of the repair of induced DNA damage was assessed by
      comet assay during further incubation of lymphocytes. Using a modified assay we
      measured simultaneously the number of single strand breaks in DNA (SSBs) and the
      sites sensitive to endonuclease III (endo III) that most probably represent
      abasic sites in DNA molecules. SO induced DNA damage in a dose-dependent manner
      and both SSBs and endo III sites were removed from the DNA by a repair process
      with a half time about 2-4 hours. The damage was repaired completely within 12
      hours after the treatment.

PMID- 14677718
TI  - A comparison of the neuroprotective efficacy of pharmacological pretreatment and
      antidotal treatment in soman-poisoned rats.
AB  - 1. To study the influence of pharmacological pretreatment (PANPAL or
      pyridostigmine combined with biperiden) and antidotal treatment (the oxime HI-6
      plus atropine) on soman-induced neurotoxicity, male albino rats were poisoned
      with a lethal dose of soman (54 (g/kg i.m.; 100% of LD50 value) and observed at
      24 hours and 7 days following soman challenge. The neurotoxicity of soman was
      evaluated using a Functional observational battery and an automatic measurement
      of motor activity. 2. Pharmacological pretreatment as well as antidotal treatment
      were able to eliminate some of soman-induced neurotoxic effects observed at 24
      hours following soman poisoning. The combination of pharmacological pretreatment
      (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment was
      found to be more effective in the elimination of soman-induced neurotoxicity in
      rats at 24 hours following soman challenge in comparison with the administration
      of pharmacological pretreatment or antidotal treatment alone. To compare both
      pharmacological pretreatments, the combination of pyridostigmine with biperiden
      seems to be more efficacious to eliminate soman-induced signs of neurotoxicity
      than PANPAL. 3. At 7 days following soman poisoning, the combination of
      pharmacological pretreatment involving pyridostigmine and biperiden with
      antidotal treatment was only able to completely eliminate soman-induced
      neurotoxic signs. 4. Thus, our findings confirm that the combination of
      pharmacological pretreatment and antidotal treatment is able not only to protect
      the experimental animals from the lethal effects of soman but also to eliminate
      most soman-induced signs of neurotoxicity in poisoned rats. The pharmacological
      pretreatment containing pyridostigmine and biperiden appears to be more
      efficacious to eliminate soman-induced neurotoxic sings than PANPAL.

PMID- 14677719
TI  - Effect of methoxime combined with anticholinergic, anticonvulsant or anti-HCN
      drugs in tabun-poisoned mice.
AB  - The effect of methoxime combined with a) atropine, b) benactyzine, c) atropine
      and natrium thiosulphate, d) atropine and diazepam on antidotal treatment
      effectiveness was studied in tabun-poisoned mice. In addition, the influence of
      pretreatment consisiting of pyridostigmine, benactyzine and trihexyphenidyle
      (PANPAL) administered 2 hours before tabun intoxication on the treatment
      effectivity of methoxime combined with e) atropine or f) benactyzine was tested.
      The most efficacious therapeutic mixture in non-pretreated mice was methoxime,
      atropine and diazepam. Natrium thiosulphate did not significantly increase
      neither decrease the antidotal treatment efficacy in comparison with methoxime
      and atropine alone. Pretreatment with PANPAL significantly decreased tabun
      toxicity (nearly 4 times in methoxime and benactyzine combination and more than 4
      times in atropine and methoxime mixture). The present study demonstrates that the
      tabun toxicity in mice is more effectively reduced when PANPAL prophylactically
      is administered than in case of treatment with methoxime and cholinergic drug
      alone. We established that anticholinergic drug option in the therapeutic mixture
      of methoxime and anticholinergic drug did not cause the difference in the
      antidotal treatment effectivities.

PMID- 14677720
TI  - Management of the infected hip arthroplasty by two-stage reimplantation.
AB  - The aim of this study is to present our experience with two-stage reimplantation
      in the management of the infected hip arthroplasty. Between January 1993 and
      December 2001 the replacement of the total hip arthroplasty in two stages was
      performed in 18 patients. There were 7 male and 11 female patients and the
      average age was 62 years. The mean follow-up after revision was 3.5 years. The
      mean postoperative Harris Hip Score averaged 78 (50-96) points. None of 18
      patients had a recurrence of the infection. Two-stage reconstruction of the
      infected hip is preferred to one-stage exchange arthroplasty at our department
      because of higher rate of eradication of the infection.

PMID- 14677721
TI  - Our approach to the conservative treatment of the dislocated hip in developmental
      dysplasia.
AB  - The purpose of this study is to evaluate the effectiveness of the use of traction
      in achieving closed reduction of a dislocated hip. We evaluated 38 hips in 29
      consecutive patients who had been treated at our department between January 1999
      and December 2001. There were 26 girls and 3 boys and the average age was 8
      weeks. The minimal duration of follow-ups was 12 months after closed reduction.
      We achieved 32 concentricaly reduced hips, the barriers to the concentric
      reduction were demonstrated by arthrography in 5 hips an 1 hip redislocated after
      removal of the spica cast. Avascular necrosis of the femoral head developed in no
      conservatively treated hip. The traction reduction method is preferred at our
      department because of high rate of success without damaging the femoral head.

PMID- 14677722
TI  - Intravascular large B-cell lymphoma presenting as cutaneous panniculitis.
AB  - In this report the case of intravascular large B-cell lymphoma (angiotropic
      lymphoma, intravascular angioendotheliomatosis, malignant endotheliomatosis) with
      panniculitis features is present. The diagnosis was based on finding of typical
      CD20 positive tumorous cells within capillaries, veins, and small arteries in the
      biopsy of subcutaneous adipose tissue. An accurate and early diagnosis together
      with combined chemotherapy resulted in good response and remission of the
      disease.

PMID- 14677723
TI  - Infective endocarditis caused by group G streptococcus with multiple cerebral
      emboli.
AB  - The group G streptococcal endocarditis is a rare form of infective endocarditis.
      In this form of infective endocarditis, serious neurological complications most
      commonly develop. We reported this case because of its being an unusual form of
      infective endocarditis that was caused by Group G Streptococcus. We also reviewed
      the literature. The patient was admitted to infectious disease service with a
      presumptive diagnosis of central nervous system infection. Blood cultures were
      positive for group G streptococcus. There was a mass on the posterior surface of
      the mitral valve which was 2 x 2.5 cm in length on the echocardiography. In the
      cranial computerized tomography of our patient, slightly increased contrast media
      uptake was observed in the both parietal lobes, in the both frontal lobes, and in
      the anterior areas of right occipital lobe. Therefore, this case was assumed as
      infective endocarditis caused by group G streptococcus with multiple cerebral
      emboli. Ceftriaxone was given for 4 weeks and gentamicin was given for 2 weeks,
      and progressive improvement of the patient's condition was seen.

PMID- 14677724
TI  - The coincidence of pure lipoma, leiomyoma, and endometrial cancer. A case report
      of the uterine tumor triplicity.
AB  - A different tumor concurrence of the uterine body is usually encountered as a
      coincidence of leiomyoma and endometrial cancer. Pure lipomatous tumors or fatty
      change in the leiomyoma or endometrium are rare affections with some diagnostic
      peculiarities. We present a case of association of the pure uterine lipoma,
      leiomyoma, and endometrial cancer as a tumor triplicity, which may contribute, to
      the pathogenesis of mesenchymal tumors in this location.

PMID- 14677725
TI  - Implementation of HIPAA.

PMID- 14677726
TI  - Volunteer opportunities: adding to a career as a professional.

PMID- 14677727
TI  - High-frequency ultrasound imaging of periocular hidrocystomas.
AB  - BACKGROUND: High-frequency ultrasound has improved our ability to manage and
      diagnose anterior segment tumors. Hidrocystomas are unusual cystic tumors that
      can affect the conjunctiva and eyelid. When they appear pigmented and rapid in
      onset, it is important to differentiate them from malignant tumors, such as
      melanoma. CASE REPORTS: Three patients were referred to The New York Eye Cancer
      Center for evaluation of pigmented lesions on their eyes. The tumors affected the
      conjunctiva or eyelid and were of recent onset ranging from 1 week to 6 months.
      The hidrocystomas displayed hypoechoic high-frequency ultrasound patterns, which
      corresponded to the cystic nature revealed through histopathological analysis.
      Differential diagnoses are discussed and include benign and malignant tumors.
      CONCLUSION: Cystic tumors are a common finding of the eye; however, pigmented
      hidrocystoma is an uncommon diagnosis. Although histopathological study is often
      required for definitive diagnosis of these lesions, much information can be
      gained through pre-surgical evaluation, particularly high-frequency ultrasound.
      Intra-lesional cyst formation was characteristic in these three tumors. Further
      study of the high-frequency ultrasound characteristics of pigmented eyelid and
      conjunctival tumors will help determine if these ultrasound characteristics are
      diagnostic.

PMID- 14677728
TI  - Coloboma of the crystalline lens.
AB  - BACKGROUND: Anomalies of crystalline lens shape and position include: lenticonus,
      lentiglobus, microspherophakia, coloboma, and ectopia lentis. Lens coloboma
      probably results from a localized absence or maldevelopment of lens zonules. It
      may be a variant of nontraumatic (congenital) ectopia lentis, in which the
      zonular deficiency is more generalized. Coloboma of the lens and nontraumatic
      ectopia lentis may occur in association with other ocular and systemic anomalies.
      A case of lens coloboma is presented, and lens coloboma, ectopia lentis, and
      associated ocular and systemic conditions are reviewed. CASE REPORT: A 36-year
      old man came to us for routine evaluation. He was found to be moderately myopic.
      Post-dilated biomicroscopy revealed a crystalline lens coloboma O.D. Since the
      patient was tall and thin, and his chest X-ray demonstrated abnormal
      cardiovascular findings, Marfan's syndrome or another connective tissue disorder
      was suspected. No definitive diagnosis was established for the patient, but he
      later reported that his sister had Marfan's syndrome, renewing suspicion that he
      also had the condition. He was advised to wear polycarbonate spectacles and to
      avoid contact sports. CONCLUSIONS: Coloboma of the crystalline lens and
      nontraumatic ectopia lentis may occur in isolation or with other ocular
      pathologies, and may reflect an underlying systemic disorder. Optometric
      management must address safety issues to reduce the risk of retinal detachment
      and lens dislocation. Systemic evaluation should be pursued to rule out Marfan's
      syndrome and similar disorders. Genetic investigation and evaluation of family
      members may also be merited.

PMID- 14677729
TI  - Glaucoma case report: a nutritional response.
AB  - BACKGROUND: Primary open-angle glaucoma (POAG) is a leading cause of blindness in
      aging adults. Intraocular pressure is one clinical sign of this complex chronic
      disease. Treatment is currently limited to intraocular pressure reduction.
      Despite advances in intraocular pressure management and treatment, primary open
      angle glaucoma patients can experience significant vision loss. CASE REPORT:
      Clinical findings in a case involving primary open-angle glaucoma are reported.
      RESULTS: A patient with primary open-angle glaucoma had intraocular pressure that
      medical treatment was unable to control. After nearly four years of medical
      therapy, intraocular pressure (IOP) suddenly decreased by 45%. A patented
      nutritional supplement was used coincident to IOP reduction. CONCLUSIONS:
      Nutritional factors may be relevant in this case of 45% intraocular pressure
      lowering.

PMID- 14677730
TI  - Accommodative response to PRIO Computer Vision Tester versus printed text.
AB  - BACKGROUND: Video display terminals (VDTs) have Gaussian display characteristics.
      Research suggests that patients accommodate differently to Gaussian images. In
      the present study, we asked if the accommodative response to the PRIO Computer
      Vision Tester (a Gaussian image) is different than the accommodative response to
      a Monocular Estimation Method (MEM) printed text target. METHOD: A normally
      sighted prepresbyopic group of subjects (N = 60) was recruited from the student
      body of Nova Southeastern University. Low neutral retinoscopy was performed on
      each subject at a distance of 50 cm. using both the PRIO vision tester and an MEM
      target. RESULTS: The PRIO vision tester and the printed text provided essentially
      the same measures of accommodative response. In addition, the luminance of the
      PRIO dropped by nearly 40% over the course of 1 hour of intermittent use.
      CONCLUSION: The PRIO vision tester and traditional nearpoint retinoscopy provided
      essentially the same measures of accommodative response in prepresbyopic
      subjects. Further studies should be considered to evaluate whether the change in
      luminance of the PRIO system has any effect on the measurement of accommodative
      response.

PMID- 14677731
TI  - Take a good close look.

PMID- 14677732
TI  - Ocular allergy.

PMID- 14677733
TI  - Acronymesis: the exploding misuse of acronyms.

PMID- 14677734
TI  - The benefits of off-pump coronary bypass: a reality or an illusion?

PMID- 14677735
TI  - Full-sternotomy off-pump versus on-pump coronary artery bypass procedures: in
      hospital outcomes and complications during one year in a single center.
AB  - We prospectively compared, according to their preoperative clinical profiles, the
      in-hospital outcomes of patients operated on consecutively (but without
      randomization) for isolated coronary artery disease with on-pump or off-pump
      techniques. During 2001, 324 patients underwent coronary artery bypass grafting:
      216 patients (mean age, 66.7 +/- 8.9 years; range, 41-85 years) underwent on-pump
      revascularization, and 108 patients (mean age, 676 +/- 10 years; range, 37-90
      years) underwent full-sternotomy off-pump revascularization. The 2 groups were
      homogeneous with regard to female sex (22.6% vs 26.8%), previous cardiac
      operation (2.8% vs 4.6%), cardiogenic shock (1.3% vs 1.9%), diabetes (30% vs
      33%), and chronic renal failure that required hemodialysis (3% vs 3.5%).
      Postoperative complications, including bleeding, myocardial infarction, acute
      renal failure, mediastinitis with sternal dehiscence, cerebrovascular events, and
      prolonged respiratory assistance were more frequent in on-pump patients (P =
      0.004). The total number of grafts and the grafts per patient ratio were
      significantly higher in on-pump patients (P = 0.0001), whereas the total number
      of full arterial revascularizations was higher in off-pump patients (P = 0.0001).
      Off-pump patients showed a significantly shorter intensive care unit stay (P =
      0.02), and less need for intra-aortic balloon pump insertion (P = 0.04). In
      hospital mortality was 2.8% in on-pump patients and 2.7% in off-pump patients (P
      = NS). Although the hospital mortality rate was comparable for the 2 techniques,
      the in-hospital comparison between the 2 groups showed how the avoidance of
      cardiopulmonary bypass can significantly reduce the cumulative postoperative
      incidence of complications in patients undergoing coronary artery bypass
      grafting.

PMID- 14677736
TI  - Diagnostic value of D-dimer and antithrombin-III levels in predicting prosthetic
      heart valve thrombosis.
AB  - The aim of this prospective study was to investigate the diagnostic value of
      plasma D-dimer levels and antithrombin-III activity in predicting prosthetic
      valve thrombus. The study group comprised 97 consecutive patients with prosthetic
      heart valves (59 with mitral, 21 with aortic, and 17 with both mitral and aortic
      prostheses) and 35 healthy control subjects. Six patients presented with symptoms
      of obstruction; the remaining 91 were asymptomatic. Patients were evaluated by
      both transthoracic and transesophageal echocardiography. Asymptomatic
      nonobstructive thrombus was detected in 13 patients (13%), whereas obstructive
      thrombus was demonstrated in all symptomatic patients. Plasma antithrombin-III
      levels of patients with prosthetic valve thrombi were slightly lower than those
      of patients without thrombus and of the control group, but the difference was not
      statistically significant. However, significantly higher plasma D-dimer levels
      were observed in patients with prosthetic valve thrombi, compared with patients
      without thrombus and the control group (735 +/- 633 microg/L, 372 +/- 342
      microg/L, and 228 +/- 219 microg/L, respectively). Valve thrombus, the prosthetic
      heart valve itself, and INR levels were identified as major determinants of
      plasma D-dimer levels. A plasma D-dimer level of >445 microg/L predicted the
      presence of a prosthetic valve thrombus with 57.8% sensitivity and 83.3%
      specificity (positive predictive value, 47.8%; negative predictive value, 87.8%).
      Current data suggest that increased plasma D-dimer levels can be clinically
      helpful in predicting the presence of prosthetic valve thrombus. Plasma
      antithrombin-III activity does not seem to have a diagnostic value in predicting
      prosthetic valve thrombi.

PMID- 14677737
TI  - Determinants of gastrointestinal complications in cardiac surgery.
AB  - We designed this study to define determinants of gastrointestinal complications
      after cardiac surgery. From January 1992 through December 2000, 11,058 patients
      underwent cardiac surgery on cardiopulmonary bypass at our institution. Data were
      prospectively collected and univariate and multivariate analyses conducted. A
      total of 147 gastrointestinal complications occurred in 129 patients (129/11,058;
      1.2%) including gastroesophagitis (18, 12.2%), upper gastrointestinal hemorrhage
      (42, 28.6%), perforated peptic ulcer (7, 4.7%), cholecystitis (10, 6.8%),
      pancreatitis (13, 8.8%), intestinal ischemia (17, 11.5%), colitis (18, 12.2%),
      diverticulitis (5, 3.4%), intestinal occlusion (2, 1.1%), lower gastrointestinal
      hemorrhage (1, 0.7%), and mixed gastrointestinal complications (14, 9.5%).
      Patients with gastrointestinal complications were significantly older and had
      significantly higher comorbidity (unstable angina, chronic renal failure, and
      peripheral vascular disease), morbidity (prolonged mechanical ventilation,
      intraaortic balloon pumping, bleeding, acute renal failure, stroke, and
      infection), and mortality rates (22.5% vs 4%, P < 0.0001). They also had longer
      cardiopulmonary bypass times and higher valvular surgery rates. Multivariate
      analysis identified 6 independent predictors for gastrointestinal complications:
      prolonged mechanical ventilation (odds ratio [OR], 5.5), postoperative renal
      failure (OR, 4.2), sepsis (OR, 3.6), valve surgery (OR, 3.2), preoperative
      chronic renal failure (OR, 2.7), and sternal infection (OR, 2.4). Factors such as
      mechanical ventilation, renal failure, and sepsis are the stronger predictors for
      GI complications, causing splanchnic hypoperfusion, hypomotility, and hypoxia.
      Furthermore, excessive anticoagulation after valve replacement may lead to GI
      hemorrhage. Valve surgery, often requiring anticoagulation, increases bleeding.
      Monitoring mechanical ventilation and hemodynamic parameters, adopting early
      extubation and mobilization measures, preventing infections, and strictly
      monitoring renal function and anticoagulation may prevent catastrophic abdominal
      complications.

PMID- 14677738
TI  - Discrete subaortic stenosis: surgical outcomes and follow-up results.
AB  - Discrete subaortic stenosis, which is an obstructing lesion of the left
      ventricular outflow tract, remains a surgical challenge. The recurrence rate is
      high despite sufficient conventional resection. We retrospectively reviewed the
      results of surgery for discrete subaortic stenosis at our institution from
      September 1995 through March 2001. Twenty-one patients with this lesion underwent
      surgical treatment during this period. Excision of the fibromuscular membrane
      with myectomy was performed in all of the patients. Follow-up in all patients
      ranged from 7 to 67 months (mean follow-up period, 39.57 +/- 15.46 months). The
      mean systolic gradient between the left ventricle and the aorta decreased from
      59.23 +/- 35.38 mmHg preoperatively to 9.47 +/- 9.91 mmHg postoperatively. There
      was no instance of heart block that required a permanent pacemaker, nor of
      bacterial endocarditis. There was no early or late postoperative death. A 22nd
      patient, who had 3+ aortic regurgitation, required aortic valve replacement and
      was excluded from the study. Two of the patients (9.5%) underwent reoperation
      because of recurrent gradient and residual ventricular septal defect. Our results
      suggest that fibromuscular membrane excision combined with myectomy in patients
      with discrete subaortic stenosis produces sufficient relief of obstruction with
      low morbidity.

PMID- 14677739
TI  - Post-traumatic pseudoaneurysm of the brachial artery and its surgical treatment.
AB  - The frequency of peripheral artery aneurysms in the upper extremities is much
      less than in the lower extremities. Diagnosis and surgical treatment are
      important because upper extremity aneurysms can cause severe decreases in
      function and lead to the loss of an arm or of fingers. We performed aneurysmal
      resection together with saphenous vein graft interpositioning in 9 patients with
      a diagnosis of post-traumatic brachial pseudoaneurysm from January 1995 through
      February 2003. Of these patients, 7 were men (77%). The mean age was 38.2 years
      (range, 26-46 years. Four patients had gunshot wounds (44%) and 5 had stab wounds
      (56%). The mean duration from injury to hospital admission was 26.7 months
      (range, 17 months-7 years). All patients underwent color-flow arterial Doppler
      ultrasonography and selective upper extremity digital subtraction angiography. In
      all patients, we performed aneurysmal resection and saphenous vein graft
      interpositioning. There was no instance of death or ischemic extremity loss.
      Patients were discharged from the hospital a mean of 3.2 days after surgery
      (range, 2-6 days). Early and late graft patency rates were 100%. We followed the
      patients' cases for a mean of 3.4 years (range, 1 month-7 years). Very rarely,
      post-traumatic upper extremity pseudoaneurysms show symptoms after a long period
      of time. Diagnosis is very easy with a review of the patient's history and a
      physical examination; surgical reconstruction is the preferred treatment for such
      patients.

PMID- 14677740
TI  - The role of brain natriuretic peptide in the prediction of cardiac performance in
      coronary artery bypass grafting.
AB  - The relationship between brain natriuretic peptide and cardiopulmonary bypass has
      not been examined sufficiently. In this study, we prospectively examined brain
      natriuretic peptide levels in the plasma of 26 patients undergoing coronary
      artery bypass grafting. Brain natriuretic peptide measurements were carried out
      at 4 times: preoperatively, 3 hours after institution of cross-clamping, 24 hours
      after institution of cross-clamping, and on the 5th postoperative day. In
      addition, we measured individual variables and compared them to brain natriuretic
      peptide levels. Mean preoperative brain natriuretic peptide levels were
      significantly higher in patients with histories of myocardial infarction (P =
      0.0047) and heart failure (ejection fraction < or = 0.40) (P = 0.0001). There was
      a significant correlation between preoperative brain natriuretic peptide levels
      and cross-clamp times (P = 0.028), and an inverse correlation between those
      levels and preoperative cardiac indices (P = 0.001). The preoperative brain
      natriuretic peptide level also correlated inversely with left ventricular
      ejection fraction before (P = 0.001) and 5 days after (P = 0.01) operation. When
      the Clinical Severity Scoring System was applied, preoperative brain natriuretic
      peptide plasma concentrations in 19 patients with risk scores of 0-2 were
      significantly lower than in the 7 patients whose risk scores were 3-6 (P =
      0.006). There was also a significant relationship between preoperative brain
      natriuretic peptide plasma concentrations and the postoperative requirement for
      inotropic agents (P = 0.027). This study suggests that plasma brain natriuretic
      peptide concentration could be one of the predictors of risk in patients
      undergoing coronary artery bypass grafting.

PMID- 14677741
TI  - Plasma volume and outcome in pulmonary hypertension.
AB  - Poor survival in pulmonary hypertension is known to be associated with
      unfavorable hemodynamic variables, including elevated right atrial pressure,
      elevated mean pulmonary artery pressure, and low cardiac index. However, the
      effect of plasma volume on outcome has not been evaluated. Our goal was to study
      the spectrum of plasma volume distribution in patients with pulmonary
      hypertension and to determine whether plasma volume could provide any prognostic
      insight in these patients. Our pilot study comprised 11 patients (aged 46 +/- 16
      years; 7 women) who were undergoing pulmonary artery catheterization before
      vasodilator therapy. In all 11 patients, plasma volume was measured, with use of
      < 25 microCi 131I-radioiodinated serum albumin. Patient follow-up averaged 19
      months. There were 2 deaths. The 2 patients who died had the highest right atrial
      pressures in the group: > or = 17 mmHg. Those 2 patients also had 2 of the 3
      highest plasma volumes at > or = 8.4%. None of the patients underwent lung
      transplantation. The propensity for elevated plasma volume and right atrial
      pressure in patients who died in this pilot study is consistent with the advanced
      right-sided heart failure that occurs in the terminal stages of pulmonary
      hypertension. Elevated plasma volume may be a useful prognosticator; further
      studies are needed to assess whether manipulation of plasma volume affects
      prognosis.

PMID- 14677742
TI  - Benzocaine-induced methemoglobinemia: a potentially fatal complication of
      transesophageal echocardiography.
AB  - We describe the cases of 2 patients who developed benzocaine-induced
      methemoglobinemia after the administration of benzocaine as premedication for
      transesophageal echocardiography. The use of intravenous methylene blue resolved
      the cyanosis in both patients. Physicians who perform procedures involving the
      application of topical anesthesia need to be aware of this side effect to prevent
      morbidity and mortality.

PMID- 14677743
TI  - Extensive retroperitoneal fibrosis with duodenal and ureteral obstruction
      associated with giant inflammatory aneurysm of the abdominal aorta.
AB  - We report a case of abdominal aortic aneurysm complicated by retroperitoneal
      fibrosis with both duodenal and bilateral ureteral obstruction. The patient
      underwent successful bilateral transurethral ureteral stenting, and then he was
      referred for surgical treatment of the aneurysm. Massive retroperitoneal fibrosis
      was found at surgery, and the mass was removed along with the diseased aorta,
      which was replaced by a bifurcated Dacron prosthesis; duodenolysis and
      ureterolysis were concomitantly performed. Ureteral stents were removed on the
      8th postoperative day. Follow-up assessment at 1 year showed normalization of the
      urinary tract structure at echography and good hemodynamic performance of the
      vascular prosthesis at Doppler examination. To our knowledge, no other case of
      duodenal and bilateral ureteral stenosis secondary to massive retroperitoneal
      reactive fibrosis in association with abdominal aortic aneurysm has been
      reported.

PMID- 14677744
TI  - Graves' disease and pulmonary hypertension: report of 2 cases.
AB  - A possible association between hyperthyroidism and pulmonary hypertension has
      been reported. We describe 2 patients who had pulmonary hypertension associated
      with Graves' disease, both of whom experienced prompt hemodynamic and symptomatic
      recovery after normal thyroid function was restored. An autoimmune mechanism
      associated with vascular endothelial damage appears to have played a key
      pathogenic role in the development of pulmonary hypertension in these patients.

PMID- 14677745
TI  - Transradial intracoronary catheter-aspiration embolectomy for acute coronary
      embolism after mitral valve replacement.
AB  - An anticoagulated 51-year-old woman with a mechanical mitral prosthesis, which
      had been implanted 12 years earlier, sustained an acute anterior wall myocardial
      infarction caused by an embolus in the mid left anterior descending coronary
      artery. After treatment with tissue-plasminogen activator failed to lyse the
      obstruction, we performed intracoronary catheter-aspiration embolectomy via a
      transradial approach, which yielded a favorable result.

PMID- 14677746
TI  - A 29-year-old Harken disk mitral valve: long-term follow-up by echocardiographic
      and cineradiographic imaging.
AB  - An 81-year-old woman was evaluated for prosthetic mitral valve function. She had
      received a Harken disk mitral valve 29 years earlier due to severe mitral valve
      disease. This particular valve prosthesis is known for premature disk edge wear
      and erosion. The patients 2-dimensional Doppler echocardiogram showed the
      distinctive appearance of a disk mitral valve prosthesis. Color Doppler in
      diastole showed a unique crown appearance, with initial flow acceleration around
      the disk followed by convergence to laminar flow in the left ventricle.
      Cineradiographic imaging revealed normal valve function and minimal disk erosion.
      We believe this to be the longest reported follow-up of a surviving patient with
      a rare Harken disk valve. We present images with unique echocardiographic and
      cineangiographic features.

PMID- 14677747
TI  - Mycotic ascending aortic pseudoaneurysm secondary to pseudomonas mediastinitis at
      the aortic cannulation site.
AB  - During the last 5 years, postoperative Pseudomonas mediastinitis has occurred in
      2 of the 3,072 patients in our institution who have undergone cardiopulmonary
      bypass cardiac operations via a sternotomy. To our knowledge, there is no prior
      report in the English-language literature of postoperative Pseudomonas
      mediastinitis that originated at the aortic cannulation site, yet that was the
      site of origin in both of these patients. The 1st patient developed a mycotic
      pseudoaneurysm of the ascending aorta at the cannulation site, secondary to the
      development of Pseudomonas mediastinitis following aortic valve replacement. This
      sequela was successfully treated by means of aneurysmectomy and closure of the
      aorta with a bovine pericardial patch, under cardiopulmonary bypass with
      circulatory arrest. The 2nd patient developed pseudoaneurysm and perforation of
      the aorta at the cardioplegia needle site, secondary to Pseudomonas mediastinitis
      following aortic and mitral valve replacement. This patient died. In both
      patients, the cannulation site and the cardioplegia needle site had been closed
      with pledgeted sutures. Pseudomonas aeruginosa was cultured from both sites. Once
      the diagnosis of Pseudomonas mediastinitis is made following heart surgery, the
      patient should undergo reoperation, if possible, for removal of the foreign
      bodies (pledgeted sutures). In addition, these patients should be monitored with
      chest magnetic resonance angiography every 3 months for 1 year, in order to
      diagnose early development of a mycotic pseudoaneurysm and subsequent
      complications.

PMID- 14677748
TI  - Management of intramural hematoma of the ascending aorta and aortic arch: the
      risks of limited surgery.
AB  - We present the case of a 57-year-old woman who had an intramural hematoma of the
      ascending aorta and aortic arch. After initial blood pressure control and imaging
      studies, the patient underwent limited surgical repair that consisted of
      ascending aortic replacement. One week postoperatively, the aortic arch hematoma
      progressed to a full dissection that extended into the proximal descending aorta.
      Emergent aortic arch replacement was required. Current world medical literature
      regarding thoracic aortic intramural hematoma is presented. This case supports
      the treatment of intramural hematomas of the ascending aorta and arch by surgical
      replacement of both segments with a Dacron graft, with the patient under deep
      hypothermic circulatory arrest.

PMID- 14677749
TI  - Diaphragmatic defect with peritoneopericardial communication.
AB  - An 81-year-old man had a congenital defect of the central tendon of the
      diaphragm, including a peritoneopericardial communication with herniation of the
      omentum to the pericardial sac in front of the heart. In addition, he had a
      critically stenosed congenital bicuspid aortic valve and severe coronary artery
      disease. The patient underwent reduction of the herniated omentum into the
      abdominal cavity, coronary artery bypass grafting, aortic valve replacement, and
      closure of the peritoneopericardial communication with a synthetic patch. Three
      years later, the patient was doing well, with a normally functioning pericardial
      valve in the aortic position and no sign of omentum around the heart.

PMID- 14677750
TI  - Correction of coarctation of the aorta with simultaneous off-pump myocardial
      revascularization.
AB  - We describe the single-stage surgical management of aortic coarctation and
      coronary artery disease in a 48-year-old man. Through a left thoracotomy, patch
      aortoplasty with a preserved bovine pericardial patch, and off-pump grafting of
      the circumflex and left anterior descending coronary arteries with a saphenous
      vein were performed. The patient had an uneventful recovery.

PMID- 14677751
TI  - Acute aortic dissection with an aorta-right atrium fistula.
AB  - We describe a rare complication of an acute aortic dissection. Proximally the
      dissection propagated into the right atrium, resulting in an aorta-right atrium
      fistula. The clinical course, operative findings, and operative treatment are
      discussed.

PMID- 14677752
TI  - Pneumopericardium and pneumomediastinum in an adolescent after blunt chest
      trauma.

PMID- 14677753
TI  - Cardiac involvement in a bronchial carcinoma. Demonstrated by contrast-enhanced
      electron-beam computed tomography.

PMID- 14677754
TI  - Right luxation of the heart after pericardial rupture caused by blunt trauma.

PMID- 14677755
TI  - Emergent surgery for massive pulmonary embolism on the basis of clinical
      diagnosis.

PMID- 14677756
TI  - Hemopericardium complicating acute myocardial infarction.

PMID- 14677757
TI  - NPY: its occurrence and relevance in the female reproductive system.
AB  - Neuropeptide Y (NPY), an amidated peptide composed of 36 amino acid residues, is
      the most widely distributed neuropeptide that performs a broad spectrum of
      physiological functions in both the central and peripheral nervous systems. Among
      numerous other actions, this peptide is involved, at the periphery, in the neural
      regulation of blood pressure and blood flow through the organs, and also, acting
      via Y2 and/or Y5 receptors, in the regulation of angiogenesis. NPY influences
      blood vessels via its own Y receptors, predominantly of the Y1 subtype. As a
      sympathetic co-transmitter NPY causes vasoconstriction, stimulates vascular
      growth and potentiates the contractile activity of noradrenaline (NA), and as a
      parasympathetic neurotransmitter it is involved in the regulation of
      vasodilatation within e.g. the uterine artery. In the female reproductive system,
      NPY not only regulates the blood flow, but also the contractile activity of non
      vascular smooth muscle cells of the uterus and oviduct, as well as the secretory
      function of the ovary. Both the concentration of NPY and its influence on the
      blood flow through the female reproductive organs are finely tuned by
      fluctuations in the concentration of ovarian steroid hormones. Thus, the present
      review was aimed at summarizing the current knowledge dealing with the
      physiological relevance of NPY in the regulation of female gonad and genital
      tract function, with a special regard to the pig as a model animal.

PMID- 14677758
TI  - Specific distribution pattern of nerve fibers containing catecholamine
      synthesizing enzymes, neuropeptide Y (NPY) and C-terminal flanking peptide of NPY
      (CPON) in the pineal gland of the chinchilla (Chinchilla laniger)--an
      immunohistochemical study.
AB  - The sympathetic nerve fibers originating from the superior cervical ganglia and
      supplying the pineal gland play the most important role in the control of the
      pineal activity in mammals. NPY and CPON are also present in the majority of the
      pinealopetal sympathetic neurons. In this study, immunohistochemical techniques
      were used to demonstrate the existence and coexistence of tyrosine hydroxylase
      (TH), dopamine beta-hydroxylase (DbetaH) as well as NPY and CPON in the nerve
      fibers supplying the chinchilla pineal gland. Ten two-year-old female chinchillas
      housed in natural light conditions were used in the study. The pineals were fixed
      by perfusion. ABC immunohistochemical technique and immunofluorescence labelling
      method were employed. TH-immunoreactive (TH-IR) varicose nerve fibers were
      observed in the pineal gland as well as in the posterior commissural area. Within
      the chinchilla pineal gland, TH-IR nerve fibers were located in the capsule and
      connective tissue septa. Numerous varicose TH-IR branches penetrated into the
      parenchyma and formed a network showing the highest density in the proximal
      region of the gland. In the central and distal parts of the pineal parenchyma, a
      subtle network, composed of thin varicose nerve branches, was observed. Double
      immunostaining revealed that the majority of TH-IR nerve fibers was positive for
      DbetaH or NPY. TH- and DbetaH-positive neuron-like cells were observed in the
      proximal region of the gland. The pattern of pineal innervation immunoreactive to
      CPON was similar to the innervation containing NPY, TH and DbetaH. The chinchilla
      intrapineal innervation containing TH, DbetaH, NPY and CPON is characterized by
      the higher density in the proximal part of the gland than in the middle and
      distal ones. The specific feature of the chinchilla pineal is also the presence
      of single TH/DbetaH-immunoreactive neuron-like cells in the proximal part of the
      gland.

PMID- 14677759
TI  - Differences in the chemical coding of nerve fibres supplying major populations of
      neurons between the caudal mesenteric ganglion and anterior pelvic ganglion in
      the male pig.
AB  - The present study was designed to investigate and to compare the chemical coding
      of nerve fibres supplying major populations of neurons in the caudal mesenteric
      (CaMG) and anterior pelvic (APG) ganglion in juvenile male pigs (n=5) using
      double-labelling immunofluorescence. The co-existence patterns of some
      biologically active substances including tyrosine hydroxylase (TH) and vesicular
      acetylcholine transporter (VAChT) as well as vasoactive intestinal polypeptide
      (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), Leu5-enkephalin
      (LENK) and serotonin (5-HT) were analysed under a confocal laser scanning
      microscope. Profound differences in the neurochemical features of the nerve
      terminals between the ganglia were observed. Moreover, there were also distinct
      differences in the chemical coding of nerve fibres associated with the particular
      populations and subpopulations of neurons within the ganglia. In both ganglia,
      nearly all adrenergic and cholinergic neurons were supplied with VAChT-positive
      nerve fibres (putative preganglionic fibres). However, in the CaMG, they were
      more numerous and, in contrast to the APG, many of them also stained for VIP. In
      the APG, a great number of nerve terminals expressed immunoreactivity to SP and
      CGRP (putative collaterals of sensory neurons). Interestingly, they densely
      supplied almost exclusively adrenergic neurons. SP-positive nerve fibres were
      moderate in number in the CaMG, but, in addition to VAChT-IR nerve terminals, the
      most numerous populations of nerve fibres in this ganglion were those expressing
      highly colocalized immunoreactivities to CGRP and LENK, and those which stained
      for 5-HT (putative processes of enteric neurons). However, these fibres supplied
      almost exclusively larger, intensely stained for TH and clustered adrenergic
      neurons. This diversity of the nerve terminals reflects the complexity of nerve
      circuits involved in the innervation of structures supplied by neurons in the
      porcine CaMG and APG. It also demonstrates the importance of nerve inputs for the
      proper function of autonomic neurons and thus their target tissues.

PMID- 14677760
TI  - Effect of vitamin E on follicular cell proliferation and expression of apoptosis
      associated factors in rats with 6-N-propyl-2-thiouracil-induced goitrogenesis.
AB  - We have investigated immunohistochemically the effect of dl-alpha-tocopherol
      (vitamin E) on thyroid gland with 6-n-propyl-2-thiouracil (PTU)-induced
      hypothyroidism in rats. The animals were divided into four groups. Rats in group
      I were designated as control, rats in group II were treated with injections of
      PTU (10 mg/kg) for 15 days, rats in group III were treated with injections of
      PTU+vitamin E (10 mg/100 g) for 15 days. Rats in group IV were treated with
      injections PTU for 15 days and kept for 15 next days after cessation of PTU
      treatment. At the end of experiment, the animals were killed by decapitation,
      blood samples were obtained, thyroid tissues were collected and processed for
      quantitative evaluation of immunohistochemical PCNA (marker of cell
      proliferation), Bax (pro-apoptotic marker) and Bcl-2 (anti-apoptotic marker)
      staining. There was an increase in the number of PCNA-immunopositive cells in
      follicular epithelial cells of group II rats compared with other groups (p<0.05).
      After vitamin E treatment, the number of PCNA-immunopositive cells decreased
      (p<0.05) while the number of Bax-immunopositive cells increased (p<0.05). The
      number of Bcl-2-positive follicular epithelial cells of group IV rats was higher
      than in those of other groups (p<0.05). The results of this study indicate that
      hypothyroidism induces cell proliferation in the thyroid gland and vitamin E may
      promote involution of the gland.

PMID- 14677761
TI  - Pneumadin in the ventral prostate and seminal vesicles of estradiol-treated rats:
      RIA and immunocytochemical studies.
AB  - Pneumadin (PNM) is a decapeptide (the rat peptide: Tyr-Gly-Glu-Pro-Lys-Leu-Asp
      Ala-Gly-Val-NH2) isolated from mammalian lungs. Human and rat PNM differ only by
      substitution of one amino acid--Tyr/Ala. PNM evokes an antidiuretic effect via a
      potent stimulation of arginine-vasopressin (AVP) release. By means of recently
      established, highly specific RIA method, high concentration of PNM had been found
      in the rat ventral prostate. Castration resulted in a profound drop in PNM
      concentration, an effect prevented by testosterone replacement. The present
      studies were aimed at investigating the effect of prolonged estradiol
      administration on PNM concentration, content and localization in the prostate and
      seminal vesicles of the rat. Depo estradiol (estradiolum valerianicum)
      administration to adult male rats resulted in a notable atrophy of ventral
      prostate and seminal vesicles. During the entire experiment (till day 30 after
      administration), PNM concentration in ventral prostate was similar to that seen
      in intact animals, while peptide content per gland was markedly lowered. PNM
      immunostaining was observed in prostate epithelium of estradiol-treated rats and
      its localization resembled that observed in intact animals. Nearly 40 times lower
      PNM concentration than in ventral prostate was found in seminal vesicles. In
      contrast to prostate, on days 20 and 30 of estradiol treatment PNM concentration
      in seminal vesicles was higher than in intact rats. However, due to profound
      seminal vesicle atrophy, PNM content per entire gland was notably lowered in
      estradiol-injected rats. By immunocytochemistry, PNM-immunoreactive substances
      were not found in seminal vesicles of either intact or estradiol-administered
      rats. High PNM concentration in the rat prostate suggests its important role in
      the function of the gland.

PMID- 14677762
TI  - The delay of anoikis due to the inhibition of protein tyrosine dephosphorylation
      enables the maintenance of normal rat colonocyte primary culture.
AB  - Apoptosis induced by detachment of cells from the extracellular matrix (anoikis)
      appears to be one of the main obstacles in attempts to establish long-term
      primary culture of normal colonocytes. In the present study, the dynamics of
      molecular events related to apoptosis of isolated normal rat colonocytes was
      investigated. The whole colonic crypts were isolated using collagenase/dispase
      digestion technique. DNA fragmentation typical for the apoptosis and the
      apoptotic morphology of cells were observed already at the end of their
      isolation. Considerable increase in caspase-3 activity was noted during the first
      two hours of cell cultivation. Delaying of apoptosis by treatment of cells with
      sodium orthovanadate, the specific protein tyrosine phosphatase inhibitor, was
      found to be possible. It may facilitate long-term culture of intestinal
      epithelial cells.

PMID- 14677763
TI  - Induction of apoptosis by EGCG in selected tumour cell lines in vitro.
AB  - One of the best recognised polyphenols of plant origin, epigallocatechin-3
      gallate (EGCG) is contained mainly in green tea and in grapes. Studies performed
      in vivo and in vitro have demonstrated high probability of anti-neoplastic
      potential of the compound, due to its capacity to induce programmed cell death.
      The present studies were aimed at evaluation of apoptosis induction in cells of
      three selected tumour cell lines, subjected to action of various concentrations
      of EGCG. The experiment was performed on cultures of HEp-2 laryngeal carcinoma
      cells, LoVo colon carcinoma cells, HeLa cervical carcinoma cells and on normal
      myoepithelial cell line, HS. EGCG was found to induce apoptosis in cells of the
      examined neoplastic lines in a dose-related manner. Moreover, effect of EGCG on
      normal cells of HS line was found to be much less pronounced as compared to
      effects exerted on sensitive neoplastic cells.

PMID- 14677764
TI  - Modulation of CD40L antigen expression in Jurkat cells: involvement of protein
      kinase C activity.
AB  - The CD40L expressed on activated CD4+ T cells delivers contact-dependent
      proliferative and anti-apoptotic signals to B lymphocytes. Little is known about
      molecular mechanisms of constitutive expression of CD40L on some non-Hodgkin's
      lymphomas, especially about involvement of two signal pathways regulating its
      expression in normal cells; one involving calcineurin, and the other protein
      kinase C. We analyzed by flow cytometry the effects of 6-hour stimulation of both
      pathways (stimuli: PMA and ionomycin) and their inhibitors: cyclosporin A and
      chelerythrine, on CD40L expression. Two Jurkat clones differing in CD40L surface
      expression: clone 217.6 (CD40L-) and 217.7 (CD40L+) were studied. Our experiments
      showed that high level of CD40L expression on the surface of 217.7 cells was
      reduced after stimulation with PMA. The same effect was observed for combination
      of PMA and chelerythrine or for PKC inhibitor alone. In 217.6 cells, only
      chelerythrine used alone induced low level of CD40L expression, while PMA and
      ionomycin were without effect. These results suggest that CD40L surface
      expression is mainly dependent on protein kinase C activity. By using PepTag
      Assay we have confirmed that in both Jurkat clones PKC activity is higher than in
      normal blood lymphocytes.

PMID- 14677765
TI  - Microvascular density in chronic pancreatitis and pancreatic ductal
      adenocarcinoma.
AB  - Chronic pancreatitis and pancreatic adenocarcinoma represent two pathologic
      phenomena with marked production of connective tissue stroma containing numerous
      small blood vessels. The aim of this study was to characterise quantitatively the
      vascular supply of pancreatic adenocarcinoma and fragments of the periductal
      tissue collected from patients with chronic pancreatitis. The study material
      included 18 cases of pancreatitis and 22 cases of pancreatic ductal
      adenocarcinoma. Microvessels were marked using monoclonal anti-CD34 antibodies.
      The number of blood vessels in the fibrous stroma was significantly higher in the
      chronic pancreatitis samples compared to the pancreatic carcinoma group (mean
      vessel count 298 and 194 vessel/mm2; median 251 and 187 vessel/mm2 respectively;
      p<0.01). Distributions of the vascular diameter in both studied groups were very
      similar. The obtained results suggest that the development of vascular network
      accompanying chronic pancreatitis is more effective in some parts of pancreas
      compared to angiogenic intensity in pancreatic adenocarcinoma.

PMID- 14677766
TI  - Development of a directly compressible poly(ethylene oxide) matrix for the
      sustained-release of dihydrocodeine bitartrate.
AB  - The purpose of this study was to design and evaluate a directly compressible
      hydrophilic poly(ethylene oxide) (PEO) matrix for the oral sustained delivery of
      dihydrocodeine bitartrate (DHCT). A direct compression method was used to prepare
      PEO matrices, and the amount of PEO in the matrices was varied to optimize in
      vitro DHCT release profiles. In vitro release studies indicated that the matrices
      containing 20%-70% w/w of PEO with molecular weight of 5.0 x 10(6) showed a
      similar release profile, as estimated with DT50%, to that exhibited by a marketed
      product, DHC Continus. In vivo bioavailability study revealed that the difference
      in the pharmacokinetic parameters such as AUC0-30 and Tmax of the selected
      sustained-release formulation containing 60% w/w of PEO 5.0 x 10(6) and DHC
      Continus was statistically insignificant (p > 0.05). Thus, it could be concluded
      that the extent of bioavailability of the sustained-release formulation developed
      here was similar to that of DHC Continus although Cmax values of these two
      preparations were significantly different (p < 0.05). From the data obtained in
      this research, hydrophilic PEO matrices were found to be a novel sustained
      release carrier for the oral delivery of DHCT.

PMID- 14677767
TI  - Multivariate methods in the development of a new tablet formulation.
AB  - The overall objective of this article is to use an efficient approach to find a
      suitable tablet formulation for direct compression. By using traditional
      approaches to statistical experimental design in tablet formulation, the number
      of experiments quickly grows when many descriptive variables or many excipients
      are included. To facilitate the screening process, a multivariate design, which
      allows a systematical evaluation of a large number of excipients with a limited
      number of experiments, was implemented. Formulations with acceptable values for
      disintegration time and crushing strength were obtained with some of the
      formulations in the present study. The multivariate experimental design strategy
      yielded PLS models that will be used to identify a region of interest for the
      optimization. The strategy is general and can be applied in many different areas
      of pharmaceutical research and development.

PMID- 14677768
TI  - Conditioning following powder micronization: influence on particle growth of
      salbutamol sulfate.
AB  - Micronization is a high-energy process that induces changes in the crystallinity
      of materials. As a result, the crystalline structures on the particles' surface
      are being destroyed and amorphous areas are formed. After micronization of
      salbutamol sulfate to be used in dry powder inhalers, only small amounts of
      amorphous material are produced. Nevertheless, even these small amounts can have
      important effects on the physical stability of the powder. The amorphous state is
      thermodynamically unstable and tends to convert to the stable, crystalline state.
      The recrystallization process of disordered regions on the particles' surface
      leads to particle growth of milled particles. In this case, bridges of solid
      material are being formed between the individual particles, which leads to
      particle growth. This is an undesirable process, because particles for pulmonary
      administration are designed to range between 1 and 10 microm in diameter to exert
      respirative effect. In the present investigation, salbutamol sulfate is
      micronized by an air jet mill, and the generated products are exposed to
      different conditions. Thereafter, the best possible conditioning parameters and
      storage conditions for the micronized salbutamol sulfate are worked out and
      rated. The aim of this treatise is to demonstrate the importance of conditioning
      following micronization.

PMID- 14677769
TI  - Improvement of dissolution and bioavailability of nitrendipine by inclusion in
      hydroxypropyl-beta-cyclodextrin.
AB  - A significant increase in solubility and dissolution rate of nitrendipine, a
      slightly soluble calcium channel blocker, was achieved by inclusion complexation
      with hydroxypropyl-beta-cyclodextrin (HP-beta-CD). The inclusion complex was
      prepared by solvent evaporation method and characterized by phase solubility
      method, x-ray diffractometry, infrared spectroscopy, and differential scanning
      calorimetry. The solubility of nitrendipine increased linearly as a function of
      HP-beta-CD concentration, resulting in AL-type phase solubility diagram which
      revealed a formation of inclusion complex in a molar ratio of 1:1, with the
      apparent association constant of 108.3M(-1). The in vitro dissolution rate of
      nitrendipine in pH 7.4 phosphate buffer was in the order of inclusion complex,
      physical mixture, and nitrendipine powder. These three different forms of
      nitrendipine were administered orally to rats with a dose of 10 mg/kg equivalent
      to nitrendipine. The AUC of inclusion complex was significantly larger than that
      of nitrendipine powder. Tmax of inclusion complex was significantly shorter and
      Cmax was significantly higher than those of nitrendipine powder. Cmax of physical
      mixture was higher than that of nitrendipine powder. Tmax of physical mixture,
      however, remained the same. The results indicated that the bioavailability of
      nitrendipine could be improved markedly by inclusion complexation, possibly due
      to an increased dissolution rate.

PMID- 14677770
TI  - Evaluation of surface and bulk characteristics of cellulose I powders in relation
      to compaction behavior and tablet properties.
AB  - The particle properties and solid-state characteristics of two celluloses, Avicel
      PH101 and cellulose obtained from the alga Cladophora sp., were evaluated and
      related to the compaction behavior and the properties of the tablets made from
      them. The surface area of the celluloses was measured at different levels of
      penetration capacity, ranging from external surface area of particles to
      molecular texture with Blaine permeametry, Kr-gasadsorption, and solid-state NMR.
      The important cellulose fibril surface area was best reflected by solid-state
      NMR, although for the Cladophora cellulose, Kr-gas adsorption also resulted in a
      surface area of the order of what has been suggested earlier on the basis of the
      cellulose fibril dimensions. The difference in fibril dimension and, thereby, the
      fibril surface area of the two celluloses was shown to be the primary factor in
      determining their properties and behavior. Properties such as the crystallinity
      and the tablet disintegration could be related to the fibril dimensions. The
      Cladophora cellulose resulted in rather strong compacts that still disintegrated
      rapidly. The irregular surface morphology of the particles and the fragmenting
      behavior of Cladophora probably contributed to the strength of the tablets.

PMID- 14677771
TI  - Preparation and evaluation of high drug content particles.
AB  - To determine how to prepare high drug content particles using a Wurster fluidized
      bed to determine realizing the miniaturization of solid dosage forms, aspirin was
      selected as the model drug and granulated without any additive. In this study,
      the emphasis was on evaluating the key operation factors of airflow rate and
      atomizing flow volume. The properties of the resulting particles, such as the
      average diameter, particle strength, appearance, and compressibility using
      different airflow rates and atomizing flow volumes, were investigated.
      Furthermore, detailed optimization of the operation conditions was conducted by
      artificial neural network (ANN) analysis. The relationship between the
      controlling factors (powder supplied, concentration of spray liquid, the amount
      of consumed spray liquid, and spray rate) and the response variables (product
      yield, median diameter, angle of repose, and degradation of aspirin) was
      investigated after evaluating the airflow rate and atomizing flow volume effects.
      The resulting granules under optimum operation conditions showed excellent
      physicochemical properties such as particle size uniformity, flowability, and
      compressibility.

PMID- 14677772
TI  - Stability indicating HPTLC determination of linezolid as bulk drug and in
      pharmaceutical dosage form.
AB  - A simple, selective, precise, and stability-indicating high-performance thin
      layer chromatographic method of analysis of Linezolid both as a bulk drug and in
      formulations was developed and validated in pharmaceutical dosage form. The
      method employed TLC aluminium plates precoated with silica gel 60F-254 as the
      stationary phase. The solvent system consisted of toluene-acetone (5:5, v/v).
      This system was found to give compact spots for Linezolid (Rf value of 0.29 +/-
      0.01). Linezolid was subjected to acidic, alkali hydrolysis, oxidation, and
      photodegradation. The degraded products also were well separated from the pure
      drug. Densitometric analysis of Linezolid was conducted in the absorbance mode at
      254 nm. The linear regression data for the calibration plots showed good linear
      relationship with r2 = 0.997 +/- 0.001 in the concentration range of 300-800
      ng/spot. The mean value of correlation coefficient, slope, and intercept were
      0.998 +/- 0.003, 0.15 +/- 0.009, and 19.52 +/- 1.66 respectively. The method was
      validated for precision, accuracy, ruggedness, and recovery. The limits of
      detection and quantification were 20 ng/spot and 50 ng/spot, respectively. The
      drug undergoes degradation under acidic and basic conditions, oxidation and photo
      degradation. All the peaks of degraded product were resolved from the standard
      drug with significantly different Rf values. This indicates that the drug is
      susceptible to acid-base hydrolysis, oxidation, and photo degradation.
      Statistical analysis proves that the method is reproducible and selective for the
      estimation of the said drug. Because the method could effectively separate the
      drug from its degradation products, it can be used as a stability indicating one.

PMID- 14677773
TI  - Talc functionality as lubricant: texture, mean diameter, and specific surface
      area influence.
AB  - Talc is widely used as a glidant (flow regulator) for powders. This study
      highlights the characteristics that confer to talcs new end use properties in
      improving the lubrication function during compression. We studied the
      contribution of texture, mean diameter (D50), and specific surface area on the
      residual die pressure, the ejection pressure, the lubrication index, and the
      tablet hardness. Different textures were studied: microcrystalline,
      macrocrystalline, and moderately macrocrystalline talc grade. The compression
      parameters were improved according to the texture. D50 varies from 0.62 to 15
      microm. As D50 decreases, the lubrication performance is improved. Finally, the
      specific surface area of talcs was studied. This last characteristic of talcs was
      shown as the most relevant parameter in determining lubrication ability.

PMID- 14677774
TI  - Characterization of excipient and tableting factors that influence folic acid
      dissolution, friability, and breaking strength of oil- and water-soluble
      multivitamin with minerals tablets.
AB  - The goal of this study is to characterize the formulation and processing factors
      that influence folic acid dissolution from oil- and water-soluble multivitamin
      with minerals tablet formulations for direct compression. The following
      parameters were studied: bulk filler solubility, soluble to insoluble bulk filler
      ratio, triturating agent (preblending carrier) solubility, disintegrant usage,
      compression pressure, and folic acid particle size. Folic acid particle size was
      determined by using light microscopy, and surface area was measured by using BET
      adsorption. The tablets were compressed on an instrumented Stokes B2 tablet
      press, and the friability, weight variation, and dissolution were measured
      according to USP methods, along with tablet breaking strength. In summary, we
      found the following factors to be critical to folic acid dissolution: bulk filler
      solubility (soluble fillers, such as maltose, increase folic acid dissolution);
      disintegrant amount (levels less than 0.4% (w/w) are ineffectual, whereas levels
      greater than 1.2% (w/w) did not further increase dissolution); and compression
      force (generally, maltose produce harder tablets). In addition, folic acid
      dissolution was less affected by changes in compaction pressure when a "super"
      disintegrant and maltose, as a bulk filler, were used. It was determined that the
      trituration agent did not play a significant role in folic acid dissolution. In
      the range of parameters studied, statistical analysis found no significant
      interactions between the parameters studied, which means they act independently
      in an additive manner. The results also show that no one factor is completely
      responsible for dissolution failure. Thus, it is the combination of formulation
      factors and processing conditions that collectively add up to produce dissolution
      failure; however, the use of a disintegrant and a soluble filler such as maltose
      can make a formulation more robust to the inevitable changes that can occur
      during commercial production.

PMID- 14677775
TI  - Continuous release of interleukin-2 from liposomal IL-2 (mixture of interleukin-2
      and liposomes) after subcutaneous administration to mice.
AB  - Recombinant interleukin-2 (IL-2) was strongly and almost completely adsorbed onto
      small and hydrophobic liposomes by simple mixing under optimal conditions
      (liposome: DSPC-DSPG; molar ratio, 10:1; 30-50 nm in size, ratio of IL-2 to
      liposome: 4.0 JRU/nmol lipid). This liposomal IL-2 displayed better distribution
      after intravenous administration in mice and improved therapeutic effect against
      experimental M5076 metastases, as reported previously. In this study, the
      elimination of IL-2 from the dosing area was investigated when the liposomal IL-2
      was administered to mice subcutaneously. The results suggest that the release of
      IL-2 from this liposome was continuous and almost complete. The mean residence
      time (MRT) of IL-2 in the dosing area was 11.0 +/- 1.65 hr. This resulted in the
      8-fold times enhancement of MRT in the systemic circulation by the presence of
      liposomes, and IL-2 was detected in the serum for 2 days. Using this liposomal IL
      2 is expected to have the potential to decrease the number of injections and
      enhance the efficacy of IL-2 in immunotherapies and therapies against tumor.

PMID- 14677776
TI  - Effectiveness of child case management services for offspring of drug-dependent
      women.
AB  - Female drug users and their children have many medical and psychosocial problems,
      yet they often fail to follow through with prescribed treatments. The present
      study describes a specialized, case management program for children, birth
      through age 2, exposed to drugs in utero. Evaluation of program efficacy was
      examined by comparing 2-year outcomes for women who received different
      intensities of these child case management services. Mothers who received higher
      intensity care were more likely to be abstinent from illicit drugs and to have
      retained custody of their child(ren) at 2-year follow-up than those with lower
      intensity services. Study findings support clinical and economic efficacy of this
      model of care.

PMID- 14677777
TI  - Personality differences associated with smoking experimentation among adolescents
      with and without comorbid symptoms of ADHD.
AB  - This study evaluated differences in adolescent personality (novelty seeking, harm
      avoidance, and reward dependence), lifetime cigarette smoking, and symptoms of
      Attention-Deficit/Hyperactivity Disorder (ADHD) among 1051 youths enrolled in
      several public high schools in middle Atlantic towns in the United States in 2000
      and 2001. Psychological and behavioral data were obtained via self-report on the
      Temperament and Character Inventory (personality), standard epidemiological
      survey items (smoking), and the Current Symptoms Scale (ADHD). The results
      indicated that adolescent "ever smokers" with high-normal symptoms of ADHD had
      the highest novelty seeking scores compared to all other study groups. These data
      highlight the greater "vulnerability" to smoking that is associated with novelty
      seeking and symptoms of inattention and hyperactivity. To the extent that novelty
      seeking and ADHD share cognitive and/or behavioral elements that may negatively
      impact upon youths' ability to attend to tobacco control communications,
      additional research on ways to adjust the delivery and content of smoking
      prevention and intervention program messages to meet the needs of these
      adolescents is warranted.

PMID- 14677778
TI  - Generalizing the alcohol outlet-assaultive violence link: evidence from a U.S.
      midwestern city.
AB  - This study assessed the geographic association between rates of assaultive
      violence and alcohol-outlet density in Kansas City, Missouri. Data were obtained
      for sociodemographic factors, alcohol-outlet density, and rates of assaultive
      violence across 89 inner-city census tracts in Kansas City, Missouri.
      Hierarchical regression analysis indicated that sociodemographic variables
      predicted 61% (R2 = 0.61) of the variance in assaultive violence, but that an
      additional 9% (R2 = 0.09) of the variability in assaultive violence was explained
      by the density of alcohol outlets. Alcohol-outlet density contributed
      significantly to the explained variance of the regression model and was
      associated with higher rates of assaultive violence in this midwestern city.

PMID- 14677779
TI  - Longitudinal effects of age at onset and first drinking situations on problem
      drinking.
AB  - The purpose of this study was to describe aspects of the first alcohol-use
      experience, and examine the predictive relations among age of first use, context
      of alcohol use initiation, and problem drinking with and without controls for
      psychosocial risk factors. Data were from the Rutgers Health and Human
      Development Project, a five-wave, prospective study of substance-use behaviors in
      a community sample. Respondents, who were first interviewed at age 12 (1979-81)
      and most recently at age 30 or 31 (1999-2000) (N=371), reported on their first
      drinking experience, and on a range of known risk factors for alcohol abuse. Most
      alcohol initiation occurred during a family gathering. Regardless of initiation
      context, youth who drank at an early age were more likely than youth who
      initiated later to become problem drinkers, although the risk was relatively
      greater for the youth who first drank outside a family gathering. Based on
      multivariate logistic regressions, feeling drunk at initiation was the only onset
      related variable significantly associated with problem drinking; other
      significant risks factors included male gender, delinquency, and family history
      of alcoholism. Because most initiation occurs at a family gathering, alcoholism
      prevention research may benefit from examining the role that drinking in family
      contexts could play with regard to socializing young drinkers to less risky
      drinking behaviors in adulthood. In particular, further research focusing on the
      subjective effects experienced by youth when they first drink may be merited.

PMID- 14677780
TI  - Attitudes and beliefs about 12-step groups among addiction treatment clients and
      clinicians: toward identifying obstacles to participation.
AB  - Participation in 12-step groups (12SG) during and after formal treatment has been
      associated with positive outcome among substance users. However, the
      effectiveness of 12SG may be limited by high attrition rates and by low
      participation, areas on which there has been little research. Clinicians play an
      important role in fostering 12-step participation, and the insights which they
      develop in their practice can greatly contribute to informing the research
      process. Yet, little is known about clinicians' attitudes about 12-step groups or
      about their experiences in referring clients. This study surveyed clients (N =
      101) and clinicians (N = 102) in outpatient treatment programs to examine 12-step
      related attitudes and to identify potential obstacles to participation. Data
      collection was conducted between May, 2001 and January, 2002 in New York City.
      Both client and clinician samples were primarily African-American and Hispanic;
      32% of clients reported substance use in the previous month, with crack and
      marijuana cited most frequently as the primary drug problem. On average,
      clinicians had worked in the treatment field for 8 years. Both staff and clients
      viewed 12SG as a helpful recovery resource. Major obstacles to participation
      centered on motivation and readiness for change and on perceived need for help,
      rather than on aspects of the 12-step program often cited as points of resistance
      (e.g., religious aspect and emphasis on powerlessness). Clinicians also
      frequently cited convenience and scheduling issues as possible obstacles to
      attending 12SG. Clinical implications of these findings are discussed, including
      the importance of fostering motivation for change, the need to assess clients'
      beliefs about and experiences with 12SG on a case-by-case basis, and to find a
      good fit between clients' needs and inclinations on the one hand, and the tools
      and support available within 12-step groups on the other.

PMID- 14677781
TI  - Explaining the geographical variation of HIV among injection drug users in the
      United States.
AB  - Distinct physical and chemical types of street heroin exist worldwide, but their
      impact on behavior and disease acquisition is not well understood or documented.
      This article presents a hypothesis to explain the unequal diffusion of HIV among
      injection drug users in the United States by examining the distribution and use
      of one type of heroin--"Mexican black tar." Drawing on ethnographic, clinical,
      epidemiological, and laboratory data, we suggest that the chemical properties of
      black tar heroin promote the following safer injection practices: (1) the rinsing
      of syringes with water to prevent clogging; (2) the heating of cookers to promote
      dissolution; and (3) a rapid transition from venous injection to subcutaneous or
      intramuscular injections.

PMID- 14677782
TI  - Prenatal cocaine exposure and infant performance on the Brazelton Neonatal
      Behavioral Assessment Scale.
AB  - Drug-exposed infants did not differ from nonexposed infants on Neonatal
      Behavioral Assessment Scale (NBAS) clusters or on birth characteristics. Infants
      (n = 137) born to three groups of low-income mothers--cocaine and poly-drug-using
      mothers in a drug user treatment group (n = 76) and in a treatment rejecter group
      (n = 18), and to a nonuser group (n = 43)--were examined at 2 days and 2-4 weeks.
      The motor cluster improved and regulation of state worsened from time 1 to 2.
      There were no interactions of group by time. Regression analyses were conducted
      to see whether group differences might either emerge or disappear after removing
      effects of competing variables, but they did not. Power analysis showed that
      sample size was sufficient to have detected group differences.

PMID- 14677783
TI  - Clinician attributions and disease model perspectives of mentally ill, chemically
      addicted patients: a preliminary investigation.
AB  - Brickman et al.'s (Brickman, P., Rabinowitz, V. C., Coates, D., Cohn, E., Kidder,
      L. (1982). Models of helping and coping. American Psychologist 37:364-384.)
      models of helping and coping provided a framework by which to compare clinicians'
      attributions of blame and control among several hypothetical patients. Sixty-one
      mental health clinicians (MHCs) and addiction clinicians (ACs)--mostly master's
      level clinicians and registered nurses--rated attributions toward vignettes that
      depicted individuals with schizophrenia, alcoholism, and mentally ill, chemically
      addicted (MICA) classifications in 1995. Results indicate that MHCs attributed
      more blame to MICA patients than did ACs, but did not differ on their
      attributions of control. MHCs' and ACs' attributions of blame and control were
      generally low, consistent with a medical model. However, the endorsement of a
      disease model of alcoholism did not significantly predict the amount of blame
      attributed by the clinicians. Implications for treatment planning for MICA
      patients are discussed.

PMID- 14677785
TI  - Well-intentioned, but potentially spreading the virus.

PMID- 14677784
TI  - The impact of an outpatient program for women with substance use-related
      disorders on retention.
AB  - Meeting the needs of women manifesting substance-use disorders is a goal in
      developing treatment programs for this population. As retention in treatment is
      positively related to treatment outcome, the length of stay in outpatient
      treatment of alcohol- and other drug-dependent women in Brazil was compared
      between two programs. Data were analyzed from 181 women entering a Mixed-Gender
      Program from 1986 to 1996 and from 80 women entering a Women-Only Program from
      1997 to 1998. A greater 3-month retention rate was observed in the Women-Only as
      opposed to the Mixed-Gender Program. Moreover, the impact was more significant
      among the alcohol-dependent women. This finding suggests that the heterogeneity
      of women with substance-use disorders has to be taken into account when
      developing appropriate treatment strategies.

PMID- 14677786
TI  - Stability of atropine sulfate prepared for mass chemical terrorism.
AB  - BACKGROUND: Preparedness for chemical terrorism includes the procurement of the
      appropriate pharmacological antagonists. A large emphasis has been placed on
      having a sufficient quantity of atropine available to treat patients exposed to
      acetylcholinesterase inhibitors such as sarin. Severe exposures may necessitate
      the administration of large amounts of atropine and dictate the need to prepare
      significant quantities of extemporaneously compounded atropine solution to
      respond to mass numbers of casualties over the first 24-48 hours postexposure.
      OBJECTIVE: The objective of this project was to determine the stability of a 1
      mg/mL atropine solution prepared in multidose IV solutions of 0.9% sodium
      chloride over a 72-hr period stored at varying temperatures. METHODS: Atropine
      sulfate solution 1 mg/mL in 0.9% sodium chloride was prepared from sterile
      pharmaceutical-grade atropine sulfate powder. Multidose bags of atropine sulfate
      (100 mL) were stored at controlled temperatures of 4 degrees C to 8 degrees C, 20
      degrees C to 25 degrees C, and 32 degrees C to 36 degrees C for 3 days and
      covered with an amber occlusive cover to minimize exposure to light. Six samples
      from each bag were drawn at 6, 12, 24, 48, and 72 h after preparation and
      compared with a time zero control sample. The samples were assayed using United
      States Pharmacopeia/National Formulary (USP/NF) high-performance liquid
      chromatography (HPLC) methods for atropine sulfate injection. The USP standard of
      95% for atropine sulfate stability was used as the primary endpoint. RESULTS:
      Atropine sulfate 1 mg/mL in 0.9% sodium chloride was stable for at least 72hr at
      4 degrees C to 8 degrees C (percent initial concentration ranging from 96.5% to
      103.4%), 20 degrees C to 25 degrees C (percent initial concentration ranging from
      98.7% to 100.2%), and 32 degrees C to 36 degrees C (percent initial concentration
      ranging from 98.3% to 102.8%). Because the IV bags were protected from light
      during this study, we recommend this practice after preparing the atropine
      solution. CONCLUSIONS: The amount of atropine necessary to treat hundreds to
      thousands of victims of a chemical attack is immense. The extemporaneous
      preparation of atropine solution from pharmaceutical-grade powder eliminates
      concerns about the storage of excessive quantities of atropine. A 1 mg/mL
      solution is stable for at least 3 days, allowing for use during the most critical
      treatment periods after exposure.

PMID- 14677787
TI  - Electrophysiologic and hemodynamic effects of sodium bicarbonate in a canine
      model of severe cocaine intoxication.
AB  - OBJECTIVE: Cocaine toxicity causes myocardial depression, malignant dysrhythmias,
      and sudden death, partially due to cocaine-related myocardial sodium channel
      blockade. Because of cocaine's ability to block cardiac sodium channels, sodium
      bicarbonate (NaHCO3) has been proposed as an antidote. The hypothesis of this
      study was that NaHCO3 would correct cocaine-induced conduction abnormalities and
      resultant hemodynamic compromise in an animal model simulating severe cocaine
      intoxication. METHODS:  DESIGN: Prospective, controlled, experimental study in
      which 15 anesthetized dogs were given three successive boluses of cocaine (7
      mg/kg) and then randomized to receive NaHCO3, 2 mEq/kg (n = 8) or placebo (n =7).
      MEASUREMENTS: Arterial, left ventricular, and pulmonary artery pressures; cardiac
      output (CO); electrocardiogram (ECG); blood gases; and serum concentrations of
      cocaine were measured at baseline, at fixed time intervals after each bolus of
      cocaine, and then after administration of NaHCO3 or placebo. Statistical
      significance was determined by analysis of variance (ANOVA) for repeated
      measures. RESULTS: Seven dogs experienced significant arrhythmias, including VT,
      pulseless electrical activity, and third-degree atrioventricular block; 2 of
      these dogs expired prior to receiving NaHCO3 and were excluded. Immediately after
      administering NaHCO3, QRS duration decreased by 30% (p < 0.001), returning to
      baseline more quickly than in the control group. This effect was associated with
      a brief 30% decrease in MAP (p = NS). After NaHCO3, CO increased 78% and remained
      increased for 5 min (p < 0.007). One dog converted from complete heart block to
      sinus rhythm shortly after NaHCO3 administration. CONCLUSIONS: NaHCO3 improved
      ECG changes secondary to cocaine toxicity and improved myocardial function.

PMID- 14677788
TI  - Oral decontamination with calcium or magnesium salts does not improve survival
      following hydrofluoric acid ingestion.
AB  - Hydrofluoric acid (HF) ingestion may result in rapid death from systemic fluoride
      poisoning. Because fluoride binds calcium and magnesium, oral administration of
      calcium or magnesium salts has been suggested as useful therapy for HF ingestion.
      This study evaluates oral administration of calcium and magnesium salts for the
      prevention or attenuation of acute HF toxicity following oral exposure in a mouse
      model. Mixed breed CF-1 mice were randomized to treatment with a lethal-dose HF
      premixed with calcium chloride, magnesium sulfate, or deionized water by gavage.
      Average survival time for the three groups was the same. This study suggests that
      calcium- or magnesium-containing solutions do not alter the toxic effect of HF
      following oral exposure.

PMID- 14677789
TI  - Rethinking the toxic methanol level.
AB  - INTRODUCTION: Treatment thresholds for methanol poisoning are based on case
      reports and published opinion. Most guidelines recommend treatment for a methanol
      level > or = 20 mg/dL in a nonacidotic patient. No supportive data have been
      offered nor has the time of the exposure been addressed. For instance, no
      distinction has been drawn between a methanol level drawn 1 hr vs. 24 hr from
      ingestion. We analyzed all published cases of methanol poisoning to determine the
      applicability of the 20 mg/dL threshold in a nonacidotic patient, specifically
      those arriving early for care (within 6 hr) with a peak or near-peak blood
      methanol concentration. METHODS: Using predefined search criteria, a systematic
      review of the world literature was performed using MEDLINE and EMBASE. In
      addition, each article's references were hand searched for pre-1966 articles, as
      were fatality abstracts from all U.S. poison centers. Human cases were included
      if they reported a known time of a single methanol exposure, acid-base data,
      blood methanol, and blood ethanol (if not acidotic). RESULTS: Dating to 1879, 372
      articles in 18 languages were abstracted using a standard format; 329 articles
      (2433 patients) involved methanol poisoning, and 70 articles (173 patients) met
      inclusion criteria. Only 22 of these patients presented for care within 6hr of
      ingestion with an early methanol level. All but 1 patient was treated with an
      inhibitor of alcohol dehydrogenase (ADH). A clear acidosis developed only with a
      methanol level > or = 126 mg/dL. The patient that did not receive an ADH
      inhibitor was an infant with an elevated early methanol level (46 mg/dL) that was
      given folate alone and never became acidotic. Intra and inter-rater reliability
      were 0.95. CONCLUSIONS: Nearly all reports of methanol poisoning involve acidotic
      patients far removed from ingestion. The small amount of data regarding patients
      arriving early show that 126 mg/dL is the lowest early blood methanol level ever
      clearly associated with acidosis. Contrary to conventional teaching, there are
      case reports of acidosis after only a few hours of ingestion. The data are
      insufficient to apply 20 mg/dL as a treatment threshold in a nonacidotic patient
      arriving early for care. Prospective studies are necessary to determine if such
      patients may be managed without antidotal therapy or dialysis.

PMID- 14677790
TI  - Randomized controlled trial of topical aspirin in the treatment of bee and wasp
      stings.
AB  - BACKGROUND: The New South Wales Poisons Information Centre (NSW PIC) has been
      recommending the use of topical aspirin paste for bee and wasp stings since the
      early 1980s. Anecdotal evidence from calls suggested it was effective in reducing
      the swelling and duration of pain, but a literature search found no evidence to
      support this. OBJECTIVE: The objective of this study was to assess the
      effectiveness of advice given by a PIC to apply topical aspirin for the treatment
      of bee and wasp stings. METHODS: Patients were recruited from callers to the NSW
      PIC who reported a bee or wasp sting. They were randomly assigned, using a 2:1
      ratio, to two different treatment advices: to apply an ice pack (control group),
      or to apply an ice pack and topical aspirin paste (treatment group). Initial
      follow-up was within 24-48 hours. Primary outcome was the presence of swelling at
      12 hr. Secondary outcomes included the presence of pain at 12 hr, the presence of
      itchiness, and duration of redness. RESULTS: There were 37 patients who received
      treatment advice and 19 in the control group. Of the 37 patients advised to apply
      aspirin, 21 (57%) had no swelling at 12 hr compared with 14 of the 19 (74%)
      patients with ice alone (difference -17%; 95% CI: -47-12%; p = 0.26). Eighty-one
      percent (30/37) of patients advised to apply aspirin had no pain at 12 hr
      compared with (18/19) 95% of the others (-14%; 95% CI: -39-14%; p = 0.34). The
      median duration of redness was 6 hr [interquartile range (IQR): 2-48 hr] in those
      advised to apply aspirin paste compared with 2 hr (IQR: 0-10 hr) in those that
      only applied ice (p = 0.04). CONCLUSIONS: Topical aspirin paste was not effective
      in reducing the duration of swelling or pain in bee and wasp stings, and
      significantly increased the duration of redness. Symptoms rapidly subsided with
      ice alone as treatment.

PMID- 14677791
TI  - Effects of envenoming by comb-footed spiders of the genera Steatoda and
      Achaearanea (family Theridiidae: Araneae) in Australia.
AB  - BACKGROUND: The family Theridiidae (comb-footed spiders) contains the well-known
      and medically important widow spider group (Latrodectus spp.). Little is known
      about the effects of envenoming by other common members of this family.
      OBJECTIVE: The objective of this study was to determine the clinical effects of
      bites by common theridiid spiders of the genera Steatoda and Achaearanea.
      METHODS: This was a prospective cohort study of calls to Australian poison
      information centers and presentations to emergency departments. Twenty-eight
      persons with a definite bite by a spider of the family Theridiidae, excluding
      Latrodectus spp., were included where the spider was immediately collected and
      expertly identified from February 1999 to April 2002. RESULTS: There were 23
      bites by Steatoda spp. and five bites by Achaearanea spp. Steatoda bites occurred
      across Australia, throughout the year, and the majority during waking hours.
      Seventy-eight percent of bites occurred indoors and 48% while dressing indoors.
      Pain was universal and was severe in six (26%). Increasing pain in the first hour
      occurred in 30%, and the median duration of pain was 6 hr (interquartile range: 1
      12 hr). Local or regional diaphoresis did not occur. Systemic effects occurred in
      30% and included nausea, headache, lethargy, and malaise. The majority received
      no treatment: seven patients presented to a hospital (two patients received
      opiates for analgesia) and 1 patient inadvertently received intravenous redback
      spider (RBS) antivenom because the spider was initially misidentified as a RBS
      (Latrodectus). The pain and symptoms responded over 1 hr following antivenom
      administration. Bites by Achaeranea spp. caused moderate to severe persistent
      pain, but no systemic effects. CONCLUSIONS: Steatoda spp. bites or "steatodism"
      may cause prolonged pain and systemic effects similar to Latrodectus bites, but
      less severe. In severe cases, the clinical effects were almost indistinguishable
      from Latrodectus, except diaphoresis was absent, and the spiders were often
      mistaken for Latrodectus. Intravenous RBS antivenom appears to be an effective
      treatment in isolated severe cases, consistent with in vitro work. Achaearanea
      bites caused pain similar to Latrodectus bites.

PMID- 14677792
TI  - Liver function test abnormalities in users of aqueous kava extracts.
AB  - INTRODUCTION: Hepatic toxicity from manufactured herbal remedies that contain
      kava lactones has been reported in Europe, North America, and Australia. There is
      no evidence for serious liver damage in kava-using populations in Pacific Island
      societies or in Indigenous Australians who have used aqueous kava extracts. This
      article presents evidence that liver function changes in users of aqueous kava
      extracts appear to be reversible. Data from one Arnhem Land community [Northern
      Territory (NT), Australia] with 340 indigenous people older than 15 years of age
      in 2000 are used. METHODS: This study was a cross-sectional study with 98
      participants, 36 of whom had never used kava. Among 62 kava users, 23 had
      discontinued kava at least 1 year before the study. Continuing users had not used
      kava for 1 to 2 months (n = 10) or 1 to 2 weeks previously (n = 15). Some (n =
      14) had used kava within the previous 24 hr. Liver function tests were compared
      across these groups, taking into account differences due to age, sex, alcohol,
      and other substance use. RESULTS: The average quantity of kava powder consumed
      was 118 g/week, and median duration of use was 12 years (range, 1-18 years). Kava
      usage levels were less than one-half of those found in previous studies. More
      recent kava use was independently associated with higher levels of liver enzymes
      gamma-glutamyl transferase (GGT) (p < 0.001) and alkaline phosphatase (ALP) (p <
      0.001), but not with alanine aminotransferase or bilirubin, which were not
      elevated. In those who were not heavy alcohol users, only those who used kava
      within the previous 24 hr showed GGT levels higher than nonusers (p < 0.001),
      whereas higher ALP levels occurred only in those who last used kava 1 to 2 weeks
      (p = 0.015) and 24 hr previously (p = 0.005). DISCUSSION: Liver function changes
      in users of aqueous kava extracts at these moderate levels of consumption appear
      to be reversible and begin to return to baseline after 1 to 2 weeks abstinence
      from kava. No evidence for irreversible liver damage has been found.

PMID- 14677794
TI  - Polar poisons: did Botulism doom the Franklin expedition?
AB  - In 1845 the Franklin expedition left London with 2 ships and 134 men on board in
      an attempt to find the route through the Northwest Passage. The ships were built
      with state-of-the-art technology for their day, but provisioned with supplies
      from the lowest bidder. After taking on fresh provisions in the Whalefish
      Islands, off the coast of Greenland, the entire crew was never heard from again.
      Graves found on remote Beechey Island indicate that three able-bodied seamen died
      during the first winter. A note written on a ship's log, later found in a cairn,
      indicate that the expedition's leader, Sir John Franklin, died during the second
      winter entrapped on the ice, by which time 24 men had also perished. The
      remaining crew failed in their attempt to walk out of the Arctic by an overland
      route. In 1981 Owen Beattie, from the University of Alberta, exhumed the remains
      of the sailors from the three graves on Beechey Island. Elevated lead levels were
      found in all three sailors. While lead poisoning has been a leading theory of the
      cause of the crew's deaths, blamed on the crudely tinned provisions the ships
      carried with them from England, chronic lead exposure may only have weakened the
      crew, not necessarily killed them. One of three exhumed sailors also had in his
      intestine the spores of an unspecified Clostridium species. The theory put forth
      by this article is that Botulism, type E, which is endemic in the Arctic, may
      have been responsible for their deaths.

PMID- 14677793
TI  - DEET: a review and update of safety and risk in the general population.
AB  - The emergence of West Nile Virus (WNV) in North America has resulted in increased
      public awareness and utilization of insect repellents containing N,N-diethyl-m
      toluamide (DEET) in the prevention of mosquito-borne disease. Regulatory
      reassessments in North American countries have recently been completed for insect
      repellents containing DEET as active ingredient, resulting in labeling changes
      intended to minimize unnecessary exposure to special populations, including
      children. This article describes those changes, and summarizes more recent data
      relating to the pharmacokinetics, toxicology, and epidemiology of adverse effects
      associated with DEET in humans.

PMID- 14677795
TI  - Ephedrine-induced cardiac ischemia: exposure confirmed with a serum level.
AB  - The temporal association of symptoms consistent with ephedrine toxicity after
      ingestion of ephedrine-containing dietary supplements is heavily relied upon to
      confirm exposure. Few reports in the literature attempt to associate toxicity
      with serum levels of these drugs. We report a case of ephedrine-induced cardiac
      ischemia confirmed by a plasma level. A 22-year-old woman ingesting an ephedrine-
      and caffeine-containing product for 2 days presented with multiple symptoms,
      including palpitations, nausea, tremulousness, abdominal pain, and vomiting. The
      initial electrocardiogram (ECG) revealed a normal sinus rhythm with 1 mm of ST
      segment depression in leads V3 and V4, along with inverted T waves in leads V1
      V4. Her symptoms and ST segment depression resolved over several hours with
      medical management. The amplitude of her T wave inversions notably diminished
      with therapy; however, they did not completely resolve. Troponins at presentation
      and the following morning were negative, and an echocardiogram showed only trace
      tricuspid regurgitation. A serum ephedrine level, drawn approximately 6 to 7 hr
      after ingestion, was 150 ng/mL. She was discharged from the hospital after being
      instructed to avoid ephedrine-containing products.

PMID- 14677796
TI  - Hydrofluoric acid-induced burns and life-threatening systemic poisoning-
      favorable outcome after hemodialysis.
AB  - BACKGROUND: Skin contact with hydrofluoric acid (HF) may cause serious burns and
      life-threatening systemic poisoning. The use of hemodialysis in fluoride
      intoxication after severe dermal exposure to HF has been recommended but not
      reported. CASE REPORT: A 46-year-old previously healthy man had 7% of his body
      surface exposed to 71% HE Despite prompt management, with subsequent
      normalization of the serum electrolytes, recurrent ventricular fibrillation
      occurred. On clinical suspicion of fluoride-induced cardiotoxicity, acute
      hemodialysis was performed. The circulatory status stabilized and the patient
      fully recovered. High fluoride levels in the urine and serum were confirmed by
      the laboratory. DISCUSSION: There is no ultimate proof that the favorable outcome
      in this case was significantly attributable to the dialysis. However, most
      reported exposures of this magnitude have resulted in fatal poisoning. As our
      patient had normal serum electrolytes and no hypoxia or acidosis at the time of
      his arrhythmias, it was decided that all efforts should be focused on removing
      fluoride from his blood. The rationale for performing hemodialysis for this
      purpose is clear, even though such intervention is more obviously indicated in
      patients with renal failure. CONCLUSION: Hemodialysis may be an effective and
      potentially lifesaving additional treatment for severe exposure to HF when
      standard management has proven insufficient.

PMID- 14677797
TI  - Fatal hypernatremia from saltwater used as an emetic.
AB  - An adolescent boy returned home from a party and told his parents he may have
      taken some pills while there. He was given saltwater to drink, in an effort to
      induce emesis. He vomited numerous times, then seized. Hypernatremia (195 mmol/L)
      was diagnosed at the community hospital, and he was transferred to a pediatric
      intensive care facility. He suffered numerous complications and died from
      cerebral herniation. This case is presented to remind physicians of the dangers
      of this obsolete therapy.

PMID- 14677798
TI  - Photosensitivity reaction in a woman using an herbal supplement containing
      ginseng, goldenseal, and bee pollen.
AB  - Photosensitivity, an abnormal skin reaction to light, is a rare adverse event
      associated with herbal medicine use. Case reports in the literature most commonly
      implicate St. John's wort. In this report, we describe the case of a 32-year-old
      woman who suffered a phototoxic reaction after taking a dietary supplement
      containing ginseng, goldenseal, bee pollen, and other ingredients. On
      presentation, she had a pruritic, erythematous rash, localized to the sun-exposed
      surfaces of her neck and extremities. She had no significant past medical history
      and was not taking any other medications. The skin rash slowly resolved after
      discontinuation of the supplement and with treatment including subcutaneous and
      topical corticosteroids. Although the individual ingredients in this dietary
      supplement have not been associated with cases of photosensitivity, it is
      possible that the combination of ingredients may have interacted to cause this
      toxic reaction. Therefore, we recommend caution in the combining of multiple
      herbs and supplements into new formulations.

PMID- 14677799
TI  - A novel clinical pattern of visual hallucination after zolpidem use.
AB  - BACKGROUND: Zolpidem is a new hypnotic that is supposed to have fewer side
      effects than traditional benzodiazepines. Some psychotic reactions, such as
      visual or hypnagogic hallucinations, have been reported to be associated with
      zolpidem use. CASE REPORT: A young female experienced three episodes of
      hallucination associated with the use of zolpidem. The visual or hypnagogic
      hallucination happened after she had stopped zolpidem and then restarted it 2
      days later. CONCLUSION: We postulate that hypnagogic or visual hallucinations
      associated with zolpidem use may be related to rapid withdrawal and restarting of
      zolpidem. The possible mechanism may be associated with the changes in the GABAA
      receptor. Avoiding "as needed" use of zolpidem and using the lowest effective
      dose may prevent these adverse effects.

PMID- 14677800
TI  - Efficiency of high-flux hemodialysis in the treatment of valproic acid
      intoxication.
AB  - Recently, highly efficient (i.e., high volume) dialysis systems have been
      successfully introduced for the treatment of critically ill patients in the
      intensive care unit. They also can be a safer, more effective, and less costly
      alternative to traditional extracorporal techniques in the treatment of severe
      intoxication. This holds true even if the substance to be eliminated is believed
      to be a poor candidate for dialysis treatment. We report a case of successful
      treatment of potentially life-threatening intoxication, with valproic acid (VPA)
      using a GENIUS batch dialysis system for combined standard and extended high
      volume hemodialysis therapy. Concentration of VPA in the total collected
      dialysate were measured.

PMID- 14677801
TI  - Combined initial cyclophosphamide with repeated methylprednisolone pulse therapy
      for severe paraquat poisoning from dermal exposure.
AB  - The article presents a patient with severe paraquat poisoning from dermal
      exposure, who had chemical bums to more than 10% of his body surface area, serum
      paraquat level 0.13 microg/mL 60 hr after exposure, and severe hypoxemia (PaO2
      41.6 mmHg). The patient was successfully treated with combined initial megadoses
      of cyclophosphamide (15 mg/kg/day, total 2 days) with repeated methylprednisolone
      pulse therapy (15 mg/kg/day, total 6 days) and continuous dexamethasone
      administration (5 mg every 8 hr), and recovered completely without sequelae 3
      months later. This treatment deserves further investigation in future clinical
      trials.

PMID- 14677803
TI  - A fatal case of spongiform leukoencephalopathy linked to "chasing the dragon".
AB  - BACKGROUND: "Chasing the dragon" involves placing heroin on aluminum foil,
      heating it from below with a flame, and inhaling the pyrolysate through a straw.
      It has rarely been associated with the development of a progressive spongiform
      leukoencephalopathy. CASE REPORT: A 43-year-old woman presented with 2 weeks of
      bizarre behavior, forgetfulness, and slowed speech and movements. Serum,
      cerebrospinal fluid, and head computed tomography (CT) scan were normal. The
      patient progressed to coma and expired during week 4 of hospital admission. The
      family confirmed that she "chased the dragon." Cause of death at post mortem
      examination was spongiform leukoencephalopathy. CONCLUSION: The diagnosis of
      heroin pyrolysate-induced spongiform leukoencephalopathy should be considered in
      a patient with a history of "chasing the dragon" and neurobehavioral changes,
      including confusion, apathy, cerebellar signs, and motor restlessness.

PMID- 14677802
TI  - Permanent paralysis at sites of dermal exposure to chlorpyrifos.
AB  - OBJECTIVE: Poisoning with organophosphate pesticides can cause sensory and motor
      neuropathy with permanent paralysis. Paralysis at the site of dermal exposure has
      not been reported. CASE REPORT: A 61-year-old carpenter sprayed a nest of
      termites with an insecticide containing chlorpyrifos without protective equipment
      and with direct contact of pesticide solution to hands, lower arms, feet, and
      lower legs, as well as inhalation of vapors from spraying. After 30 min he became
      ill with nausea, abdominal cramping, arm and leg weakness, bilateral shoulder
      pain, chest pain, and numbness in the left hand and arm. At a hospital, he was
      treated with atropine 1 mg IV and pralidoxime Cl 2 g IV There was 0/5 strength in
      the hands and wrists and 3/5 elsewhere, a left peritoneal palsy, and urinary
      retention. He was transferred to a tertiary care hospital where paralysis
      persisted. Electromyogram studies documented widespread peripheral neuropathy.
      With continued progression of neuropathy, pralidoxime was repeated on the third
      day. By day 12, motor strength improved except for the hands and left lower leg.
      Right interosseous muscle strength was 1/5 and left was 0/5. Right-hand grip was
      2/5, and left-hand grip was 0/5. He was transferred to a rehabilitation center.
      He never regained use of his hands and was disabled from employment as a
      carpenter. There was a disturbed gait, with inability to clear his left foot with
      walking. Urinary retention persisted and required self-catherization. CONCLUSION:
      Dermal exposure of the hands and feet to chlorpyrifos was associated with atrophy
      and permanent paralysis of exposed areas. The importance of protective equipment
      is emphasized.

PMID- 14677804
TI  - Single-dose dexamemthasone-induced adrenocortical suppression in an intentional
      self-poisoning--case report.

PMID- 14677805
TI  - Carnitine.

PMID- 14677806
TI  - Role of carnitine in valproic acid toxicity.

PMID- 14677807
TI  - Do you need demonstrable ischemia for evidence-based decision-making in chronic
      stable angina?

PMID- 14677808
TI  - Osborn waves in the electrocardiogram, hypothermia not due to exposure, and death
      due to diabetic ketoacidosis.
AB  - Hypothermia usually occurs because a patient has been exposed to a cold
      environment; however, a number of nonenvironmental conditions may produce
      hypothermia. This report relates the clinical course of a patient whose
      hypothermia was due to severe diabetic ketoacidosis. In addition, we review the
      causes of hypothermia and Osborn waves beyond exposure to cold temperature.
      Hypothermia due to diabetic ketoacidosis is an uncommon complication of a common
      disease that carries with it clinically significant consequences. Accordingly, we
      believe that all clinicians should be aware of this potential complication of
      diabetic ketoacidosis and should be able to recognize the importance of the
      electrocardiogram in such patients.

PMID- 14677809
TI  - The association of homocysteine and coronary artery disease.
AB  - Hyperhomocysteinemia has been associated with increased risk of atherosclerosis
      and myocardial infarction by a number of prospective case-control studies. A
      variety of genetic mutations, nutritional deficiencies, disease states, and drugs
      can elevate homocysteine concentrations. Treatment with folic acid with or
      without B-complex vitamins effectively lowers homocysteine levels. Whether
      therapy corresponds with decreased risk of coronary events is unknown, but may be
      promising. This article reviews the biochemistry of homocysteine metabolism,
      pathogeneisis, and etiology of hyperhomocysteinemia, along with its association
      with coronary artery disease, screening, and treatment.

PMID- 14677810
TI  - Thyroid function is associated with presence and severity of coronary
      atherosclerosis.
AB  - BACKGROUND: Overt hypothyroidism has been found to be associated with
      cardiovascular disease. Moreover, subclinical hypothyroidism is a strong
      indicator of risk for aortic atherosclerosis and myocardial infarction.
      HYPOTHESIS: We hypothesized that variation of thyroid function within the normal
      range may influence the presence and severity of coronary atherosclerosis.
      METHODS: We studied a total of 100 consecutive men and women (59 men, 41 women,
      age 63.7 +/- 11.0 years) who underwent coronary angiography. Blood was tested for
      serum thyrotropin concentrations and for free tri-iodothyronine and free
      thyroxine concentrations. In addition to the assessment of thyroid function,
      conventional risk factors for coronary artery disease (CAD), clinical
      characteristics, serum lipid levels, fasting total homocysteine, and angiographic
      results of coronary artery assessment were obtained. Two experienced
      cardiologists blinded to clinical and laboratory data reviewed the cinefilms. The
      severity of CAD was scored as 0 for those with smooth normal epicardial coronary
      arteries, 0.5 for plaquing (< 50% diameter stenosis), and 1, 2, or 3 for those
      with single-, double-, or triple-vessel epicardial coronary artery stenosis of >
      50%, respectively. RESULTS: The severity of CAD was scored as 0, 0.5, 1, 2, and 3
      in 14, 26, 25, 22, and 13 patients, respectively. Higher levels of serum-free
      thyroid hormone concentrations were associated with decreased severity of
      coronary atherosclerosis. Serum-free tri-iodothyronine was 2.99 +/- 0.33 pg/ml in
      patients with a CAD severity score of 0 to 1 and 2.74 +/- 0.49 pg/ml in patients
      with CAD severity scores of 2 and 3 (p < 0.01). Moreover, serum-free thyroxine
      concentrations showed a trend toward higher levels in patients with CAD severity
      score 0 to 1 compared with patients with CAD severity scores 2 and 3 (11.65 +/-
      1.87 pg/ml vs. 10.9 +/- 2.3 pg/ml; p = 0.09). Higher levels of serum thyrotropin
      concentrations were associated with increased severity of coronary
      atherosclerosis (1.37 +/- 1.02 mU/l vs. 1.98 +/- 2.13 mU/l in patients with CAD
      severity score 0 to 1 versus CAD severity scores 2 and 3; p = 0.049). When
      grouped into three subsets according to their serum free tri-iodothyronine levels
      (< 2.79, 2.8 to 3.09, and +/- 3.1 pg/ml), the prevalence of CAD scores 2 and 3
      was significantly higher in the subset of patients with low serum free tri
      iodothyronine levels (48.5%) than in the subsets of patients with medium or high
      tri-iodothyronine concentrations (32.25 and 25%, respectively, p for trend <
      0.05). CONCLUSION: These data in patients referred for coronary angiography
      suggest that variation of thyroid function within the statistical normal range
      may influence the presence and severity of coronary atherosclerosis.

PMID- 14677811
TI  - Significance of the intima-media thickness of the thoracic aorta in patients with
      coronary atherosclerosis.
AB  - BACKGROUND: The prevalence and clinical significance of atherosclerotic aortic
      disease have now been documented in a variety of patient populations by use of
      transesophageal echocardiography (TEE). There are many reports that
      atherosclerotic aortic plaques detected by TEE are a marker for coronary artery
      disease (CAD). HYPOTHESIS: The study was undertaken to evaluate the significance
      of the intima-media thickness (IMT) and formation of atherosclerotic plaques of
      the thoracic aorta (TA) in patients with CAD, especially in terms of a
      correlation between the IMT of the TA and the extent of coronary atherosclerosis.
      METHODS: The IMT of the TA was measured using TEE. The study population comprised
      100 patients (68 men, mean age 59 years). The extent of coronary atherosclerosis
      was divided into four groups (0, 1, 2, 3) according to the number of coronary
      arteries narrowed > or = 50%. RESULTS: There was no significant difference in the
      IMT of the ascending TA according to the presence of significant (> 50% narrowed)
      coronary stenosis, but there was a significant difference in the IMT of the
      descending TA (1.39 vs. 1.88 mm, p = 0.005). There was a significant correlation
      between the extent of coronary atherosclerosis and the IMT of the ascending and
      descending TA (r = 0.24, p < 0.05; r = 0.352, p < 0.001, respectively). The
      plaques in the TA were seen in 7, 41, 52, and 65% of patients in Groups 0, 1, 2,
      and 3, respectively. Among atherosclerosis risk factors, hyperlipidemia was the
      only factor analyzed that affected the IMT of the descending TA (2.11 vs. 1.78
      mm, p < 0.05). CONCLUSION: The IMT of the TA correlates significantly with
      coronary atherosclerosis, and correlation of the descending TA IMT with coronary
      atherosclerosis is better than that of ascending TA IMT. Age is associated with
      coronary atherosclerosis, and TA IMT and hyperlipidemia are associated with
      descending TA IMT. Therefore, although TEE is not recommended for measuring TA
      IMT or for evaluating aortic plaques in patients with CAD, measurement of TA IMT
      as well as carotid artery IMT is very helpful for understanding the extent of
      coronary atherosclerosis.

PMID- 14677812
TI  - Association of aortic valve sclerosis and coronary artery disease in patients
      with severe nonischemic mitral regurgitation.
AB  - BACKGROUND: The presence of aortic valve sclerosis accounts for a higher rate of
      ischemic events and increased cardiovascular mortality. It may reflect coronary
      artery disease (CAD) because of a shared pathologic background. HYPOTHESIS: We
      aimed to analyze whether the presence of aortic valve sclerosis might help in
      identifying patients with coronary atherosclerosis among those with severe
      nonischemic mitral regurgitation (MR), who undergo coronary angiography before
      surgery for screening, and not because of suspected ischemic heart disease.
      METHODS: In all, 84 patients (mean age 64 +/- 9 years; 71% men) with mitral valve
      prolapse and severe regurgitation underwent echocardiography and coronary
      angiography. Aortic valve sclerosis was defined as focal areas of increased
      echogenicity and thickening of the leaflets without restriction of leaflet motion
      on echocardiography. Coronary artery disease was defined by the presence/absence
      of atherosclerotic plaques, independent of the degree of stenosis. RESULTS:
      Coronary artery disease was diagnosed in 47.6% of patients with and 15.8% of
      those without aortic valve sclerosis (p = 0.008). On logistic regression
      analysis, the presence of aortic valve sclerosis predicted CAD (odds ratio 3.3,
      95% confidence interval 1.03-10.5; p = 0.04) independent of age. In female
      patients, the risk ratio for CAD in the presence of aortic valve sclerosis was 9.
      CONCLUSIONS: Coronary artery atherosclerosis and aortic valve sclerosis are
      closely associated in patients with severe nonischemic MR.

PMID- 14677813
TI  - Increased plasma thioredoxin in patients with acute myocardial infarction.
AB  - BACKGROUND AND HYPOTHESIS: Thioredoxin is an important biomarker for oxidative
      stress. We investigated whether thioredoxin levels were elevated in patients with
      acute myocardial infarction (AMI) and were associated with the results of
      coronary reperfusion. METHODS: The present study determined plasma thioredoxin
      levels in 51 patients with AMI, 30 patients with stable exertional angina (SEA),
      and 30 patients with chest pain syndrome (CPS). Plasma sampling was performed on
      admission, at 12 h, 1 week, 2 weeks, and 4 weeks in patients with AMI, and after
      admission in patients with SEA and CPS. RESULTS: Plasma thioredoxin levels on
      admission were higher in patients with AMI than in those with SEA and CPS. Plasma
      thioredoxin levels in patients with AMI were decreased in 12 h without further
      change thereafter. However, thioredoxin levels in patients with AMI remained
      higher than in those with SEA. In multivariate analysis, higher levels of
      thioredoxin on admission were a risk factor for failure in emergent reperfusion
      therapy in patients with AMI independent of other factors. CONCLUSION: Plasma
      thioredoxin levels are elevated in patients with AMI, and higher thioredoxin
      levels may predict subsequent failed coronary reperfusion therapy in patients
      with AMI.

PMID- 14677814
TI  - Acute left ventricular failure after large volume pericardiocentesis.
AB  - This paper reports on two cases of large volume pericardiocentesis followed by
      transient severe acute left ventricular (LV) systolic failure in the absence of
      any prior history of LV dysfunction. Acute LV volume overload due to
      interventricular volume mismatch is believed by most authors to be the cause for
      this phenomenon. Another plausible physiopathologic explanation is the acute
      increase in "wall stress" (Laplace's law) due to acute distention of the cardiac
      chambers secondary to a sudden increase in venous return at high filling
      pressures, combined with a "vacuum" effect of the evacuated pericardial space.

PMID- 14677815
TI  - Robert A. O'Rourke.

PMID- 14677816
TI  - Tuberculosis contact investigations.

PMID- 14677817
TI  - Global elimination of tuberculosis: implementation, innovation, investigation.
AB  - The elimination of a public health menace such as tuberculosis is always an
      attractive proposition. Is it realistic to consider? Selecting elimination as a
      target engages commitment, identifies challenges and stimulates critical
      evaluation. Challenges are numerous, including the large pool of latent
      infection, the long incubation period, the inadequacy of present tools and
      strategies, poverty and its relation to tuberculosis, the dependence on declining
      health services, the negative impact of human immunodeficiency virus infection,
      and the long-term commitment required with present approaches. Although
      tuberculosis has a tragic impact in causing death and chronic illness, the target
      for elimination must remain preventing infection, and the aim to achieve a
      generation free of infection. Targeting decreased mortality or improved health
      will not be sufficient to guide the critical reflection required to eliminate the
      causative organism; this can only be achieved by focusing on preventing and
      eliminating infection. While we have an international consensus on the strategy
      for controlling tuberculosis, we must also keep in mind that it is not
      sufficient. We must improve the current strategy as well as develop new tools on
      which we can base a new strategy if we hope to achieve the objective of
      elimination of tuberculosis. Reaching the target will require commitment to
      implementing what we currently have, improving on it in every way possible and
      keeping our minds and imaginations open to new ways to approach the fight against
      tuberculosis.

PMID- 14677818
TI  - Contacts of tuberculosis patients in high-incidence countries.
AB  - The risk of acquiring infection with Mycobacterium tuberculosis correlates with
      duration of exposure to an infectious source of tuberculosis. Contact
      identification is therefore a comparatively high-yield activity. However, in
      resource-poor settings tuberculin is rarely available, and even where it is
      available, non-specific cross-reactions to tuberculin resulting from BCG
      vaccination complicate the interpretation of tuberculin test results. The
      identification of a putative infection with M. tuberculosis in a contact must
      result in intervention. Excluding active tuberculosis is mandatory before
      preventive therapy is provided. This might prove difficult in areas where the
      most and often only affordable diagnostic means is microscopy. The International
      Union Against Tuberculosis and Lung Disease (IUATLD) has thus proposed to target
      preventive therapy to healthy children below the age of 5 years living in the
      same household as a sputum smear-positive tuberculosis case, with the sole
      recourse to clinical contact examination. While this approach will lead to
      treatment of a considerable proportion of uninfected children, the advantages are
      several-fold: first, these are the easiest identifiable contacts; second, they
      are particularly prone to progression to disease if infected; third, emerging
      drug resistance is of little concern at that age; fourth, administration of
      preventive treatment can be delegated to the source case. This approach is safe,
      simple, and affordable.

PMID- 14677819
TI  - When it comes to contact notification, HIV is not TB.
AB  - HIV partner notification can help patients, partners, and disease control efforts
      in the community. The emphasis on HIV partner notification has varied widely in
      the United States. Stigma, denial, and competing priorities have limited the use
      of partner notification in many areas. Ongoing HIV transmission after the
      infection is diagnosed suggests a need for ongoing partner notification, but
      there is little evidence that this is occurring. The forces driving the evolution
      of partner notification for HIV are quite different from those acting on contact
      tracing for TB. Understanding these forces will help predict where partner
      notification is headed and may help make it more effective. In this paper we
      review partner notification for HIV, discuss effectiveness, and outline changes
      over time. A comparison with contact tracing for TB leads us to conclude that
      partner notification for HIV is very different from contact tracing for TB.

PMID- 14677820
TI  - Contact tracing: comparing the approaches for sexually transmitted diseases and
      tuberculosis.
AB  - SETTING: Literature review for the process of contact tracing for sexually
      transmitted diseases (STD) and for tuberculosis (TB), focusing on articles that
      report results of studies or commentary. OBJECTIVE: To compare and contrast
      contact tracing in order to highlight emerging commonalities. DESIGN: A
      descriptive review, based on Medline search with augmentation from other
      published and unpublished sources. RESULTS: Contact tracing for STD and TB have
      some obvious differences because of differing routes of transmission, differing
      sensibilities required to work with the affected populations, a different
      potential for anonymous contacts, and a major difference in the epidemiologic
      value of biomarkers. Nonetheless, the convergence of these processes on
      disadvantaged populations where drug use and sexual activity are important social
      factors has engendered an increasing similarity. CONCLUSION: A broadened approach
      to both, with greater attention to how ancillary contacts and associates may be
      of use in interrupting deeply embedded endemic disease transmission, deserves
      further study. Some newer approaches in the use of network-informed methods to
      elicit contacts and investigate the community dynamics of transmission may be of
      particular value in TB case investigation. These strategies will be enhanced by
      the availability of DNA fingerprinting, a powerful biomarker of recent
      Mycobacterium tuberculosis transmission and case association (a technology not
      available for STD contact tracing).

PMID- 14677821
TI  - Tuberculosis contact investigations in rural Alaska: a unique challenge.
AB  - Alaska Natives suffered extraordinary rates of disease and death from
      tuberculosis (TB) during the first half of the 20th century. Although the
      epidemic was largely controlled in the 1960s, rates of TB among Alaska Natives
      remain higher than for other Alaskans, and village outbreaks of TB continue to
      pose major threats. In 2000, a contact investigation around a case patient with
      infectious TB involved eight villages in south-western Alaska and found 26
      additional persons with TB disease and 48 people with newly positive TB skin
      tests. Rural Alaska brings unique challenges to TB contact investigations not
      seen elsewhere in the United States because many villages are accessible only by
      small aircraft or boat. To conduct an investigation, a public health nurse must
      fly into the village, bring food and water, and sleep at the village clinic or
      school. In spite of these obstacles, over the past 4 years contact investigations
      have been initiated for all TB cases with acid-fast bacilli smear-positive
      sputum, and the proportion of adequately examined contacts has increased from 51%
      to 75%. The Alaska TB Program plans to improve contact investigations through
      ongoing reports to regional public health centers and through a statewide
      training workshop.

PMID- 14677822
TI  - Tuberculosis contact investigation in a rural state.
AB  - The investigation of contacts of tuberculosis (TB) cases is an essential part of
      Mississippi's comprehensive TB program. A case interview is initiated within 24
      hours, and the concentric circle method is used to identify and evaluate
      contacts. High-risk contacts of pulmonary cases are located and evaluated within
      10 days. A follow-up evaluation is conducted by a TB consultant to determine the
      need for additional tests. All pulmonary contacts receive a 12-week follow-up
      tuberculin skin test (TST) if the initial test is negative. Directly observed
      treatment for latent TB infection (LTBI) is offered to all children aged <15
      years, human immunodeficiency virus positive persons and others deemed at high
      risk for developing active disease. Mississippi contact investigations in 1990
      1998 identified 212 (0.7%) cases of TB, and 5608 (17.5%) contacts with LTBI. In
      that period, the proportion of cases with contacts identified averaged 99%, with
      a mean number of contacts per case of 15.4. At the same time, 95% of contacts
      completed an evaluation for active TB and LTBI. Among contacts <15 years of age,
      >96% have completed LTBI treatment annually since 1992. Cases and case rates in
      Mississippi have decreased annually during this period. Effective TB contact
      investigation yields immediate results by identifying other sources of TB
      transmission and preventing future transmission through appropriate treatment of
      contacts with LTBI.

PMID- 14677823
TI  - Approaches to contact investigations in Texas.
AB  - Tuberculosis (TB) spreads when family and social contacts breathe the air exhaled
      by someone with active TB disease. Contact investigation is the most appropriate
      strategy to interrupt the transmission and subsequent development of TB. One of
      the problems associated with contact investigations in an area with a very
      diverse population has been the inability of investigations to adapt their
      methods of approach to the different circumstances of each person with TB
      disease. Through interviews and group discussions with public health field
      workers and local TB program managers across Texas, the authors have been able to
      gather information on how contact investigation practices can be customized to
      overcome barriers specific to different populations in the state and generate a
      productive outcome. Variables such as culture, language, risk factors, and
      various settings may require a different investigational approach than the
      standard, traditional approach to contact investigation. It is anticipated that
      the concept of customizing contact investigations to meet the needs of specific
      populations and circumstances will become the practice worldwide, and will be a
      useful tool in the management of contact investigations.

PMID- 14677824
TI  - Evaluation of tuberculosis contact investigations in California.
AB  - OBJECTIVE: To estimate the burden of tuberculosis (TB) contact investigations in
      California, assess outcomes and effectiveness, and identify performance gaps.
      METHODS: Aggregate program management reports were used to examine contact
      investigations conducted for pulmonary TB cases reported between 1 July 1999 and
      30 June 2000 in California. Findings were compared to national objectives, and
      performance gaps were identified. Costs were estimated, and effectiveness of TB
      case detection and prevention was assessed. RESULTS: A total of 2032 acid-fast
      bacilli sputum smear-positive and sputum smear-negative/culture-positive cases
      was reported; 17774 contacts were elicited, and 15582 (88%) contacts were
      evaluated. TB disease and latent tuberculosis infection (LTBI) were diagnosed in
      111 (<1%) and 4609 (30%) contacts, respectively; 1958 (43%) contacts with LTBI
      completed treatment. Costs of contact investigations were estimated at dollars
      4.8 million; 81% of expected TB cases were detected, but only 35% of cases
      expected to occur within 2 years following the investigation were prevented.
      CONCLUSIONS: California's performance did not meet national objectives for
      contact evaluation or treatment completion; improved effectiveness of contact
      investigations in California is needed. Although analysis of existing contact
      investigation surveillance data provided a macro-level view of performance gaps,
      expanded surveillance data are required to inform interventions.

PMID- 14677825
TI  - Standardizing contact investigation protocols.
AB  - SETTING: The State of Alabama Department of Public Health Division of
      Tuberculosis Control. OBJECTIVE: To standardize contact investigation protocols
      and implement an intervention to increase TB field worker adherence to the
      protocols with the goal of promoting efficiency and effectiveness in contact
      investigations. DESIGN: A process evaluation of existing data collection and
      management systems and protocols was performed. Standardized protocols and an
      intervention to increase TB field worker adherence to the protocols were created
      and pilot tested. These were then implemented and formative evaluation data were
      collected. RESULTS: The process evaluation revealed considerable variance among
      field workers with regard to protocols and definitions of variables related to
      contact investigations. Protocols were standardized and an intervention targeted
      at TB field workers was developed. The intervention consisted of a training
      workshop and the development of a computer-based contact investigation module.
      This was successfully implemented throughout the state. CONCLUSIONS: To perform
      effective contact investigations and conduct studies to improve the effectiveness
      of these investigations, TB control programs must pay careful attention to
      precisely defining variables and concepts related to the contact investigation.
      Furthermore, protocols must be standardized and resources devoted to training of
      TB field workers to ensure adherence to protocols.

PMID- 14677826
TI  - Using the CDC framework for program evaluation in public health to assess
      tuberculosis contact investigation programs.
AB  - SETTING: In Massachusetts, despite the efforts of state and local health
      department tuberculosis (TB) programs, the rates of contact testing and follow-up
      remain below the state and national objectives. Changes in contact investigation
      practices are therefore needed to achieve these objectives. OBJECTIVE: To develop
      contact investigation self-evaluation tools in accordance with the Centers for
      Disease Control and Prevention's (CDC) Framework for Program Evaluation in Public
      Health. These tools will be used to assess state and local level contact
      investigation practices. DESIGN: The self-evaluation tools were developed using
      the CDC's framework and pilot-tested by public health nurse case managers in five
      city health departments. The tools were revised according to feedback received
      from the nurses. RESULTS: The Massachusetts TB Division conducted three of the
      six steps of the CDC's framework. Stakeholders of the evaluation were identified
      and engaged, logic models were created describing state and local TB program
      components, and self-evaluation tools were developed. CONCLUSION: The CDC's
      framework provided a useful methodology for beginning the assessment process for
      evaluating TB contact investigation programs. When the contact investigation self
      evaluation tools are implemented statewide, the findings will be used to target
      areas in need of improvement and develop strategies to make noteworthy changes.

PMID- 14677827
TI  - Tuberculosis contact investigations: outcomes in selected areas of the United
      States, 1999.
AB  - SETTING: Twenty-nine United States jurisdictions. OBJECTIVE: To determine yields
      of tuberculosis (TB) contact investigations. METHODS: Health departments within
      the jurisdictions reported counts and outcomes from routine contact
      investigations for cases reported in 1999. RESULTS: The 29 jurisdictions reported
      9199 TB cases, 51.9% of the US and Puerto Rico 1999 total, and listed 67585
      contacts. While 571 (10.6%) of 5405 pulmonary cases confirmed by sputum
      bacteriology had no contacts listed, 13904 contacts were listed for other cases
      that were unlikely to be contagious. Diagnostic evaluation was completed for
      56100 contacts (83.0%), with 561 TB cases found. Of 13083 contacts found to have
      latent TB infection, 5746 (44.5%) completed treatment to prevent TB. Loss to
      follow-up and self-discontinuation of treatment accounted for 70% of reasons why
      treatment was not completed. CONCLUSION: Contact investigations capture
      substantial numbers of TB cases and latent TB infections, but the impact on
      prevention is limited by the poor treatment rates for infected contacts. Contacts
      should be sought for each potentially contagious TB case; why so many contacts
      are sought for cases who are unlikely to be contagious needs to be determined.

PMID- 14677828
TI  - Yield of source-case and contact investigations in identifying previously
      undiagnosed childhood tuberculosis.
AB  - OBJECTIVE: To determine the extent to which source-case investigations, in which
      a child was the index tuberculosis (TB) case, and contact investigations of adult
      pulmonary cases, identified children and adults with previously undiagnosed TB or
      latent tuberculosis infection (LTBI). METHODS: We reviewed records of 111 source
      case investigations and 38 contact investigations involving 164 TB cases among
      children <5 years of age from eight California health jurisdictions with a case
      rate greater than the state average for this age group (9.6/100000). RESULTS: In
      source-case investigations, 141 children <5 years and 113 children 5-14 years of
      age were evaluated for TB disease and LTBI. Fourteen previously undiagnosed TB
      cases were found, including seven children <5 years of age. Source-case
      investigations also identified persons who might benefit from treatment for LTBI
      (45% had a positive tuberculin reaction). In contact investigations of adult TB
      cases, 202 children <5 years and 122 children 5-14 years of age were evaluated.
      In addition to 46 children with TB <5 years of age, the basis on which these
      contact investigations were selected for study, four children 5-14 years of age
      and 10 adults were found to have TB disease. A high percentage (41%) of contacts
      with a positive tuberculin reaction was found, especially among household
      contacts. CONCLUSIONS: Source-case investigations and contact investigations are
      effective for finding previously undiagnosed cases of TB. They are also useful
      for identifying children and adults who would possibly benefit from treatment for
      LTBI. Earlier detection and treatment of adults with TB could interrupt
      transmission and be a step toward eliminating childhood TB.

PMID- 14677829
TI  - Finding contacts of homeless tuberculosis patients in New York City.
AB  - OBJECTIVE: To determine factors associated with no contacts identified for
      homeless patients in New York City. DESIGN: Culture-confirmed pulmonary
      tuberculosis cases in persons >18 years old diagnosed in 1997-1999 were included.
      Demographic and clinical characteristics of tuberculosis patients associated with
      the number of contacts identified according to homeless status were analyzed
      using unconditional logistic regression. RESULTS: Homeless patients (n = 152) had
      a significantly lower median number of contacts than non-homeless patients (n =
      2836) (1 vs. 4, P < 0.001). Among homeless patients, having AFB smear-positive
      sputum with cavitary lesions reduced the likelihood of having no contacts
      identified. Homeless patients who lived on the street at the time of diagnosis
      were more likely to have no contacts identified compared to those with contacts
      identified (61.4% vs. 56.1%); however, the difference was not statistically
      significant (P = 0.506). Unlike non-homeless patients, being hospitalized at the
      time of tuberculosis diagnosis was not associated with having contacts identified
      in homeless patients. CONCLUSIONS: Homelessness independently predicted the
      likelihood of having no contacts identified. Strategies such as interviews that
      focus on location rather than persons may be more effective for identifying
      contacts. Furthermore, being homeless at the time of diagnosis should be used as
      an indicator for prioritizing prompt contact evaluation.

PMID- 14677830
TI  - Outcomes of contact investigation among homeless persons with infectious
      tuberculosis.
AB  - SETTING: Homelessness is an important risk factor for tuberculosis (TB). Health
      departments often fail to identify contacts for homeless TB cases, but little
      else is known about the outcome of contact investigations for these cases.
      OBJECTIVE: To describe the outcomes of identification, tuberculin skin testing
      (TST), clinical evaluation and treatment for contacts of infectious homeless TB
      cases. DESIGN: Retrospective multicenter review of data of contact investigations
      conducted in 1996 by five health departments in the United States. RESULTS:
      Twenty-seven (8%) of 349 TB cases were homeless. Failure to identify contacts
      occurred in six (50%) of 12 cases residing in shelters vs. one (7%) of 15 non
      shelter cases. Of 479 contacts identified, 297 (62%) were fully evaluated, 97
      (20%) had only initial testing, and 85 (18%) were not evaluated. Of the 394
      evaluated contacts, 13 (3%) had a prior positive TST. Of the remaining 381
      contacts, six (1.6%) had active TB and 67 (17.6%) were TST-positive. Only 27
      (44%) of 61 contacts completed treatment for latent TB infection. CONCLUSION:
      Despite the failure to identify contacts for some cases, contact investigations
      for homeless TB cases identified large numbers of contacts for whom evaluation
      and treatment were often not completed. Prospective studies with more complete
      documentation are needed to improve contact investigations for homeless TB cases.

PMID- 14677831
TI  - Tuberculosis screening among immigrants holding a hunger strike in churches.
AB  - SETTING: In January 2001, approximately 600 immigrants held a sit-down and hunger
      strike in several churches in Barcelona to force the Spanish government to comply
      with demands to regulate their immigration status. Following the diagnosis of a
      case of smear-positive pulmonary tuberculosis (TB) in one of the immigrants, we
      performed a large contact investigation. OBJECTIVES: To describe contact
      investigation procedures used in this setting and to evaluate contact
      investigation results. METHODS: Demographic variables were collected, and
      tuberculin skin tests (TST) and chest radiograph examinations were performed.
      Odds ratios (OR) with 95% confidence intervals (CI) were calculated and logistic
      regression was used for multivariate analyses. RESULTS: A total of 541 TSTs were
      performed. Of these, 86% were read and 40.5% yielded a positive reaction with an
      induration >14 mm. In a multivariate analysis, the risk of presenting a TST
      induration >14 mm was found to be three times higher among those aged >35 years
      compared to those <24 years (OR 3.40; 95%CI 1.76-6.59), and for immigrants from
      Bangladesh (OR 3.14; 95%CI 1.16-6.10) and Pakistan (OR 2.04; 95%CI 1.11-3.73)
      compared to those from India. A total of 314 chest radiographs examinations were
      performed and three additional cases of TB were identified, yielding a TB
      prevalence of 0.7%. CONCLUSIONS: By focusing efforts and conducting targeted TB
      screening in this high-risk population, it was possible to complete the
      intervention in only 3 days. A high prevalence of TB infection and TB disease was
      found.

PMID- 14677833
TI  - Integrated counseling and screening for tuberculosis and HIV among household
      contacts of tuberculosis patients in an endemic area of HIV infection: Chiang
      Rai, Thailand.
AB  - SETTING: Combined hospital-based and home visit, Chiang Rai, Thailand. OBJECTIVE:
      To describe the results of screening of tuberculosis (TB) and HIV infection among
      household contacts of TB patients in an area endemic for HIV. DESIGN: Consecutive
      new smear-positive TB patients were interviewed and their household contacts were
      screened for TB including tuberculin skin test (TST), chest radiography, and
      sputum examination. Voluntary HIV testing and counseling was also performed.
      RESULTS: Of 499 pulmonary TB index cases, 197 (39.5%) were HIV-positive; 1200
      household contacts were screened for TB and 890 (74.2%) agreed to HIV testing.
      The prevalence of TST induration > or = 10 mm and active TB among household
      contacts of HIV-positive pulmonary TB cases were 46.2% (225/487) and 2.9%
      (14/490), and among household contacts of HIV-negative TB cases were 62.1%
      (438/705) and 4.4% (31/710), respectively. Higher HIV prevalence was found among
      contacts of HIV-positive TB patients than among household contacts of HIV
      negative TB index cases (52/376, 13.8% vs. 13/514, 2.5%) (P < 0.001). Spouses of
      HIV-positive TB cases had the highest HIV prevalence (36/74, 48.6%). Among the
      household contacts who were HIV-positive, 9.5% (7/74) had active TB. CONCLUSION:
      Integrated counseling and screening for TB and HIV should be provided for
      household contacts of TB patients in an HIV endemic area.

PMID- 14677832
TI  - Evaluation of an extensive tuberculosis contact investigation in an urban
      community and jail.
AB  - SETTING: Urban community and jail. OBJECTIVES/DESIGN: Evaluate outcome and
      process of an extensive tuberculosis contact investigation, including completion
      of treatment of latent TB infection (TLTBI). RESULTS: Between April 2000 and
      September 2001, 18 epidemiologically-linked tuberculosis cases were identified;
      15 were culture-confirmed, all with a matching 14-band DNA fingerprint pattern.
      The source case had cavitary pulmonary disease and had been incarcerated 4 months
      prior to diagnosis. Sixty-six of 67 (99%) community contacts and 221/344 (64%)
      jail contacts were evaluated. The presumed new infection rate was 56% for
      community contacts (11 cases, 25 tuberculin skin test [TST] positive) and 20% for
      jail contacts (6 cases, 32 TST converters). Screening results for 113 (33%) jail
      contacts were obtained in the jail TST registry upon rearrest. All identified
      cases completed treatment. Of 22 community contacts initiating TLTBI, 11
      completed (44% of infected, 50% of initiators). Of 32 infected jail contacts, 12
      initiated TLTBI (all who remained incarcerated), and 10 completed (31% of
      infected, 83% of initiators). None of 20 additional in-fected jail contacts, all
      of whose TST conversions were identified with re-arrest data, were subsequently
      located. Two additional related cases have been identified as of October 2003.
      CONCLUSIONS: Close health department/corrections collaboration facilitated this
      extensive contact investigation, which identified high Mycobacterium tuberculosis
      transmission rates and controlled the outbreak. Numerous contacts were identified
      and screened, but rates of treatment completion for infected contacts were low.
      Novel strategies are needed to maximize the number of infected contacts who are
      not only identified and evaluated, but completely treated.

PMID- 14677834
TI  - Contact investigations in congregate settings, New York City.
AB  - SETTING: Large urban tuberculosis control program. OBJECTIVE: To evaluate results
      of procedures implemented for systematic investigation of tuberculosis exposures
      in congregate settings. DESIGN: Between October 1995 and December 2000, a unit
      consisting of epidemiologists, health educators and tuberculin screening staff
      investigated exposures in sites with >15 persons. Transmission at the site was
      defined as likely, possible, unlikely or unknown. RESULTS: Among 100
      investigations, 12 were tuberculosis case clusters, five were source case
      investigations, and 83 were exposures to single infectious cases. Transmission
      was likely in 24 (21%), possible in eight (8%), unlikely in 62 (62%), and could
      not be assessed in four (4%). Among the 83 exposures to single infectious cases,
      2740 contacts were tested; 502 (18%) were infected. Among 1202 close contacts,
      996 (82%) were tested, 197 (20%) were infected and started treatment of latent
      tuberculosis infection (LTBI) and 102/197 (52%) completed treatment. Sites with
      likely transmission had index patients with longer duration of cough (13 vs. 6
      weeks, P = 0.01) and cavitary lesions (84% vs. 44%, P = 0.01) compared to sites
      with unlikely transmission. CONCLUSION: A systematic approach for conducting
      contact investigations in congregate settings is useful for assessing
      transmission. As such investigations are resource intensive and transmission is
      not common, performing tuberculin skin testing after most persons would have
      converted should be considered in low-risk groups. Additional efforts are needed
      to increase completion of treatment for LTBI in contacts identified in these
      settings.

PMID- 14677835
TI  - Analysis of the frequency distribution of tuberculin skin test readings: a tool
      for the assessment of group contact investigations.
AB  - SETTING: The public health tuberculosis control program covering Seattle,
      Washington, and its surrounding suburban areas. OBJECTIVE: To describe a tool of
      potential usefulness in the assessment of transmission of tuberculosis in contact
      investigations of groups, such as co-workers or schoolmates of an infectious
      case, with a low prior probability of latent tuberculosis infection (LTBI).
      DESIGN: Tuberculin skin test (TST) readings in mm of the group being tested were
      graphed and compared with the known frequency distributions of TST readings of
      populations with and without LTBI, the latter including a fraction with non
      specific tuberculin reactivity. RESULTS: Four group contact investigations were
      analyzed retrospectively with this tool. In two the graphed TST readings of
      contacts fell within the distribution of a population with LTBI, and suggested
      that transmission had occurred. In the other two, the graphed readings better fit
      the distribution of a population with non-specific tuberculin reactivity and
      suggested that transmission had not occurred. CONCLUSION: This simple tool to
      facilitate the determination of whether transmission of tuberculosis has
      occurred, and who should be offered treatment for LTBI in contact investigations
      of groups of people, deserves further study.

PMID- 14677836
TI  - Workplace contact investigations in the United States.
AB  - SETTING: Five state tuberculosis (TB) control programs in the United States.
      OBJECTIVES: To determine the prevalence of and treatment for latent TB infection
      (LTBI) among contacts of active TB cases identified in the workplace, and to
      describe TB control program policies for the initiation and conduct of workplace
      investigations. DESIGN: Retrospective review of health department records for all
      culture-positive pulmonary tuberculosis cases aged > or = 15 years reported in
      1996, and their contacts. RESULTS: There were 349 cases of active TB, of whom 134
      (38%) were employed. Workplace contact investigations were conducted for 42
      cases, resulting in the identification of 724 contacts. The rate of LTBI was 29%
      overall, varying by worksite from a low of 16% to a high of 51%. LTBI estimates
      were higher for fully-screened contacts of smear-positive rather than of smear
      negative index cases. However, fully-screened contacts of index patients with
      cavitary disease had lower LTBI estimates than those of index patients without
      cavitation. Treatment for LTBI was initiated in 45% of infected contacts. The
      five programs had somewhat variable policies regarding workplace contact
      investigations. Data on HIV co-infection and place of birth of contacts were
      largely missing. CONCLUSION: Factors contributing to LTBI among workplace
      contacts may include the presence of persons with pre-existing LTBI or a positive
      skin test as a result of BCG vaccination, clinical characteristics of the index
      case, and workplace environmental characteristics conducive to transmission.
      Standard guidelines for workplace investigations, written workplace investigation
      policies, and standard data collection practices are needed to better apportion
      the causes of observed infection rates in the workplace.

PMID- 14677837
TI  - Genotyping in contact investigations: a CDC perspective.
AB  - Genotyping of Mycobacterium tuberculosis isolates has been widely used to support
      investigations of outbreaks and as a tool for studying transmission dynamics and
      other aspects of tuberculosis epidemiology. Its applications to contact
      investigations are more limited. Targeted typing can be used to confirm or
      disprove suspected relationships among cases. Universal typing of isolates can be
      used to identify unsuspected transmission and broaden the scope of contact
      investigations. In order to properly use the results, one must understand the
      nature of the changes in the M. tuberculosis genome that produce the
      heterogeneity reflected in the genotypes, and understand the discriminatory power
      of the various methods. IS6110 fingerprinting provides the highest discriminatory
      power, but can be a slow process. Spoligotyping and MIRU-VNTR are PCR-based
      methods that provide faster turnaround and produce digital results that
      facilitate comparisons. Appropriately used, isolate genotyping can be a useful
      adjunct to standard contact investigations.

PMID- 14677838
TI  - The role of molecular epidemiology in contact investigations: a US perspective.
AB  - Preventing tuberculosis (TB) transmission through treatment of active cases and
      contact investigation is the highest priority of TB control programs in the
      United States. The role of contact investigation is becoming increasingly
      important as the number of TB cases declines nationally. However, the
      effectiveness of contact investigation has been difficult to assess because,
      prior to the availability of molecular genotyping techniques, levels of
      transmission were crudely measurable. Epidemiological links within and outside
      the traditional concentric circle approach are limited by the quality of the
      contact investigation, the skill and knowledge of the investigator and the
      information provided by the patient. Molecular epidemiology has added a new
      dimension by enabling the recognition of unsuspected transmission, likely
      locations of transmission, and quantification of the extent of transmission that
      is occurring within a given population. In the future, as real-time genotyping
      becomes more available, the role of molecular epidemiology is likely to expand.

PMID- 14677839
TI  - Tuberculosis contact investigation and DNA fingerprint surveillance in The
      Netherlands: 6 years' experience with nation-wide cluster feedback and cluster
      monitoring.
AB  - SETTING: The Netherlands, 1995-2000. OBJECTIVES: To describe the contribution of
      6 years of nationwide DNA fingerprint surveillance to tuberculosis control in
      general and to conventional contact investigations in particular. DESIGN: All
      Mycobacterium tuberculosis cultures are subjected to standardised IS6110-based
      RFLP typing, and clustered cases are systematically reported to the regional TB
      services involved (cluster feedback). Standardised questionnaires are used to
      collect information on contact investigations and epidemiological links (epi
      links) at regional level. Revision of the questionnaires for the period 1997-2000
      allows comparison of epi linking before and after cluster feedback. RESULTS:
      Among 2206 clustered cases, 462 (21%) epi links were expected before the RFLP
      result, whereas an additional 540 (24%) epi links were established after cluster
      feedback. Epi links based on documented exposure increased by 35%, from 357 to
      550 (P < 0.001). Only 1% of contact investigations were extended, however, and
      relatively few additional persons with active or latent tuberculosis were
      diagnosed. Reasons for the limited impact on contact investigation outcome were
      1) contact took place 1-7 years previously (51%), 2) documented contact involved
      a subsequent case in the cluster (21%), 3) casual contact (15.5%) and 4)
      different region (9%). Five per cent of epi links established by contact
      investigation were contradicted by RFLP data. Epi links were more frequently
      documented in Dutch (41%) than non-Dutch cases (19%, OR 3.0; 95%CI 1.41-1.91).
      Cluster monitoring permitted: 1) identification of transmission chains that could
      not be detected by contact investigations, 2) development and evaluation of
      targeted interventions, and 3) identification of professional failures and poor
      programme performance. CONCLUSIONS: RFLP surveillance forms the bridge between
      conventional contact investigation and other forms of targeted active case
      finding. Combining both complementary strategies in a comprehensive approach to
      systematic outbreak monitoring and management allows countries in the elimination
      phase of the disease to better target and evaluate TB control interventions.

PMID- 14677840
TI  - Results of testing for human immunodeficiency virus infection among recent
      contacts of infectious tuberculosis cases in the United States.
AB  - CONTEXT: Persons with recently acquired latent tuberculosis (TB) infection and
      human immunodeficiency virus (HIV) co-infection are at high risk of rapid
      progression to TB disease. OBJECTIVES: To determine the proportion of close
      contacts of infectious TB patients tested for HIV, and the results of HIV testing
      for this group. DESIGN, SETTING AND SUBJECTS: Review of health department records
      for all close contacts of 349 patients with culture-positive pulmonary TB aged 15
      years or older reported from five study areas in the United States in 1996. MAIN
      OUTCOME MEASURES: Proportion of close contacts of TB patients tested for HIV, and
      rate of HIV infection among close contacts of TB patients. RESULTS: A total of
      1169 close contacts were identified for 349 patients with active pulmonary TB.
      HIV test results were available for 224 (64%) TB patients and 220 (19%) close
      contacts. Of the TB patients tested, 164 (73%) were HIV-negative and 60 (27%)
      were HIV-positive. An equal proportion of close contacts of HIV-positive and 
      negative TB patients were tested (21% vs. 24%). Of the close contacts tested, 201
      (91%) were HIV-negative and 19 (9%) were HIV-positive. Compared with close
      contacts of HIV-negative TB patients, close contacts of HIV-positive TB patients
      were more likely to be HIV-positive (53% vs. 2%; P < 0.01). This association was
      observed for contacts residing in the TB patient household (70% vs. none; P <
      0.01), not residing in the TB patient household (20% vs. 4%; P < 0.05), 25-44
      years of age (88% vs. 8%; P < 0.01), and > 44 years of age (22% vs. 2%; P <
      0.05). CONCLUSIONS: HIV-positive TB patients and their close contacts may share
      some of the same risk factors for HIV infection. These findings suggest that the
      HIV status of the TB patient, in addition to established risk factors for HIV
      infection, may be an important consideration for prioritizing voluntary HIV
      counseling and testing efforts among close contacts of infectious TB patients.

PMID- 14677841
TI  - Yield of casual contact investigation by the hour.
AB  - OBJECTIVE: Among casual contacts of tuberculosis (TB) patients, to assess how
      duration of contact, prior mycobacterial exposure, and performance of one or two
      tuberculin skin tests (TST), affect the likelihood that a positive TST represents
      conversion. METHODS: Published estimates of mycobacterial prevalence and BCG
      coverage, and their effect on single or repeated TSTs, were used to calculate
      baseline prevalence of TST reactions in four populations commonly encountered in
      North American contact investigations. Using published estimates of hourly risk
      of TB infection, the probability that a positive TST represented conversion was
      calculated. RESULTS: Among casual contacts with 20 hours of exposure, the
      likelihood that a single positive TST performed after 8 weeks represented
      conversion was 77% in persons from populations with low prior mycobacterial
      exposure, but only 6-8% in foreign-born populations. If tuberculin testing was
      performed immediately and then again 8 weeks post-exposure, 14-38% of all
      positive tests would be due to boosting, related to prior exposure to
      mycobacteria or BCG. If one TST, performed 8 weeks after exposure, was positive
      in casual contacts from populations with high prevalence of prior mycobacterial
      exposures, the likelihood of true conversion was less than 40%, even after 200
      hours of exposure. CONCLUSIONS: A single TST performed 8 weeks after the end of
      exposure among casual contacts will detect all true conversions, and minimize
      misdiagnosis due to boosting. The decision to perform TST on casual contacts
      should consider the likelihood of prior mycobacterial exposure in the population,
      as well as the duration of exposure.

PMID- 14677842
TI  - A network-informed approach to investigating a tuberculosis outbreak:
      implications for enhancing contact investigations.
AB  - BACKGROUND: To elucidate networks of Mycobacterium tuberculosis transmission, it
      may be appropriate to characterize the types of relationships among tuberculosis
      (TB) cases and their contacts (with and without latent TB infection) in addition
      to relying on traditional efforts to distinguish 'close' from 'casual' contacts.
      SETTING: A TB outbreak in a US low incidence state. OBJECTIVE: To evaluate
      whether social network analysis can provide insights into transmission settings
      that might otherwise go unrecognized by routine practices. DESIGN: All adult
      outbreak-associated cases (n = 19) and a convenience sample of their contacts
      with and without latent TB infection (LTBI) (n = 26) were re-interviewed in 2001
      using a structured questionnaire. Network analysis software was used to create
      diagrams illustrating important persons within the outbreak network, as well as
      types of activities TB cases engaged in with their contacts. RESULTS: Drug use
      and drug sharing were more commonly reported among cases and their infected
      contacts than among contacts without LTBI. TB cases central to the outbreak
      network used crack cocaine, uncovering the need to focus control efforts on
      specific sites and persons involved in illicit drug use. CONCLUSION: Outbreaks
      occur even in areas with low TB incidence, frequently among groups whose drug use
      or other illegal activities complicate control efforts. TB programs should
      consider the use of network analysis as a supplement to routine contact
      investigations to identify unrecognized patterns of M. tuberculosis transmission.

PMID- 14677843
TI  - Tuberculosis infection and disease in children living in households of Filipino
      patients with tuberculosis: a preliminary report.
AB  - SETTING: DOTS Clinic with a DOTS-Plus pilot project for the management of
      multidrug-resistant tuberculosis (MDR-TB) in a high burden country. OBJECTIVE: To
      determine the prevalence of tuberculosis (TB) infection and disease among
      pediatric household contacts of patients with pulmonary TB (PTB). DESIGN: Cross
      sectional study. METHODOLOGY: One hundred and fifty-three children aged 0-15
      years in the households of 62 bacteriologically confirmed PTB patients, including
      44 with MDR-TB, were studied. BCG scars were noted, and tuberculin skin test
      (TST), screening chest radiography, and sputum or gastric aspirate smear and
      culture for Mycobacterium tuberculosis in those with radiographic findings
      suggestive of PTB were done. RESULTS: For children in this study, the prevalences
      of latent TB infection (LTBI), radiographically diagnosed pulmonary TB, and
      bacillary pulmonary TB were 69.2%, 3.3%, and 0.65%, respectively. Only age > or =
      5 years was found to be a significant predictor of LTBI (OR 3.17, 95%CI 1.43
      7.01). CONCLUSION: Contact investigation for active case-finding and early
      treatment of TB in children from households of patients with active PTB is
      essential for TB control. Further study on a more precise definition of TB
      infection and strategies for control in this population will be pursued.

PMID- 14677844
TI  - Contact investigations as a means of detection and timely treatment of persons
      with infectious multidrug-resistant tuberculosis.
AB  - SETTING: Two regions of metropolitan Lima, Peru. OBJECTIVE: To determine the
      outcomes of two contact investigation strategies used in therapy enrollment
      cohorts of patients with multidrug-resistant tuberculosis (MDR-TB). DESIGN: From
      28 August 1996 to 31 December 1999, 91 index patients received individualized MDR
      TB therapy (Group A), and from 1 October 1997 to 31 December 1999, another 101
      index patients received a standardized MDR-TB regimen (Group B). We conducted a
      retrospective chart review and home visits to identify secondary cases among
      close contacts of both of these groups. Group A secondary cases with MDR-TB
      received therapy based on the drug susceptibility profile of their infecting
      strain, while Group B secondary cases received standard short-course therapy.
      RESULTS: Among 945 close contacts, 72 secondary TB cases (8%) were found. Of 42
      who had drug-susceptibility testing, 35 (84%) were MDR-TB, but only seven (17%)
      had the same drug susceptibility profile as the index case. Cure exceeded 80% in
      Group A secondary cases, while only half of Group B secondary cases were cured
      (RR 1.6, 95%CI 1.1-2.2). CONCLUSION: Contact investigation protocols coupled with
      enrollment in MDR-TB therapy are a useful means of detecting and promptly
      treating persons with infectious MDR-TB. In settings with endemic MDR strains of
      Mycobacterium tuberculosis, effective therapy of contacts of MDR-TB patients
      requires knowledge of drug susceptibility for each contact with active disease.

PMID- 14677845
TI  - Factors associated with identifying tuberculosis contacts.
AB  - SETTING: Little is known about why some tuberculosis (TB) patients identify few
      or even no contacts. OBJECTIVES: To describe patient perceptions of the contact
      investigation interview and determine potential factors associated with
      identifying TB contacts. DESIGN: A total of 13 focus groups were conducted: 10
      groups with previously smear-positive pulmonary TB patients born in the United
      States or Mexico, and three with program staff to discuss attitudes toward and
      perceptions of the contact investigation interview. Patients were recruited into
      separate groups by country of birth and number of contacts identified. RESULTS:
      The data indicated that patients-even those who identified few contacts
      overwhelmingly reported identifying contacts easily and willingly. Understanding
      the purpose of the contact investigation and seriousness of TB facilitated naming
      contacts, while miscommunication and misconceptions about TB hindered the
      process. Patients felt strongly about informing their contacts before the health
      department contacted them. Staff respondents reported that education and
      effective communication were critical during contact investigation interviewing.
      CONCLUSION: Data indicated that patients, including those identifying few
      contacts, reported wanting to name their contacts. However, misconceptions may
      affect their understanding of who their contacts are, and hence the quantity and
      quality of the contacts identified. These findings underscore the need for
      effective communication and education.

PMID- 14677846
TI  - Bioeconomic evaluation of sow longevity and profitability.
AB  - Sow production indicators, including litter size, litter weight, and the length
      of time that sows remained in the herd (sow longevity), were used to characterize
      sow performance and profitability. Sow longevity and production records from
      148,568 sows in 32 commercial herds from Central Illinois from January 1995 to
      May 2001 were analyzed using survival and repeatability models, respectively. The
      factors studied included sow genetics (32 genetic lines), with eight major lines
      present in multiple herds, and the combination of herd and year of entry in the
      herd. The largest difference in longevity between the major genetic lines was
      approximately one parity. There were differences (P < 0.05) in the instantaneous
      sow removal rate or hazard from the major lines. These differences constitute
      evidence that sow longevity could be improved by using replacements from specific
      genetic lines. The net present value per sow (present value of future cash flows
      and the present value of the sow) was used to evaluate the effect of sow
      longevity and production traits on economic returns. Assuming a zero discount
      rate per parity, genetic lines with longer herd life resulted in greater profit
      than genetic lines with shorter herd life. This difference was reduced with
      increasing discount rates and was reversed with high discount rates and low net
      income per litter. These results suggest that the magnitude of the economic
      improvement attained through the use of sow genetic lines with longer longevity
      depends on the economic context under which the evaluation is made.

PMID- 14677847
TI  - Production and economic potentials of cattle in pasture-based systems of the
      western Amazon region of Brazil.
AB  - Our objectives were to evaluate strategies to improve productivity and economic
      returns from beef and dual-purpose cattle systems based on data collected on one
      dual-purpose (Bos taurus x Bos indicus) and two beef (Nellore) cattle farms in
      the western Amazon region of Brazil. Forage chemical composition and digestion
      rates of carbohydrate fractions of grazed Brachiaria decumbens and Brachiaria
      brizantha cv. Marandu grasses and Pueraria phaseoloides (tropical kudzu) legume
      were measured monthly during a 9-mo period from the end of one dry season to the
      end of the subsequent rainy season. Measurements of milk and growth responses to
      grazing these forages were used to predict animal productivity responses to
      dietary nutrient availability throughout an annual cycle. The ME available for
      gain in our simulations was always more limiting than metabolizable protein. The
      predicted ME available for gain was 0.50 kg/d for steers grazing B. brizantha and
      0.40 kg/d for finishing steers grazing B. decumbens. Grasses contained more NDF
      and neutral detergent insoluble protein and less ME (P < 0.05) in the rainiest
      months than in the less rainy season, which resulted in 20% less predicted weight
      gain by growing steers (P < 0.05). Supplementation with sorghum grain was
      required to increase milk production and growth by 25 or 50% per animal,
      respectively, but this strategy was less profitable than current forage-only
      diets. Greater productivity of land and labor from higher stocking indicated
      greater net margins for beef production, but not for milk. This study suggested
      that more intensive beef production by judicious fertilization of grass-legume
      pastures and greater stocking density is the preferable strategy for owners of
      these cattle systems to improve economic returns under current conditions. It
      also might help decrease the motivation for additional forest clearing.

PMID- 14677848
TI  - Quantitative trait loci analysis for growth and carcass traits in a Meishan x
      Duroc F2 resource population.
AB  - We constructed a pig F2 resource population by crossing a Meishan sow and a Duroc
      boar to locate economically important trait loci. The F2 generation was composed
      of 865 animals (450 males and 415 females) from four F1 males and 24 F1 females
      and was genotyped for 180 informative microsatellite markers spanning 2,263.6 cM
      of the whole pig genome. Results of the genome scan showed evidence for
      significant quantitative trait loci (<1% genomewise error rate) affecting weight
      at 30 d and average daily gain on Sus scrofa chromosome (SSC) 6, carcass yield on
      SSC 7, backfat thickness on SSC 7 and SSC X, vertebra number on SSC 1 and SSC 7,
      loin muscle area on SSC 1 and SSC 7, moisture on SSC 13, intramuscular fat
      content on SSC 7, and testicular weight on SSC 3 and SSC X. Moreover, 5%
      genomewise significant QTL were found for birth weight on SSC 7, average daily
      gain on SSC 4, carcass length on SSC 6, SSC 7, and SSC X and lightness (L value)
      on SSC 3. We identified 38 QTL for 28 traits at the 5% genomewise level. Of the
      38 QTL, 24 QTL for 17 traits were significant at the 1% genomewise level.
      Analysis of marker genotypes supported the breed of origin results and provided
      further evidence that a suggestive QTL for circumference of cannon bone also was
      segregating within the Meishan parent. We identified genomic regions related with
      growth and meat quality traits. Fine mapping will be required for their
      application in introgression programs and gene cloning.

PMID- 14677849
TI  - Investigation of breeding strategies to increase the probability that German
      shepherd dog and Labrador retriever dog guides would attain optimum size.
AB  - An optimum-sized dog guide weighs 18 to 32 kg and measures 53 to 64 cm in height
      at the withers when mature body size is attained. Effects of selection index with
      and without restrictions, independent trait selection, directional selection,
      stabilizing selection, and negative assortative mating were modeled using data
      from German shepherd dogs and Labrador retrievers raised by the Seeing Eye, Inc.,
      Morristown, NJ from 1979 to 1997. The selection goals were to decrease mature
      weight and mature height in German shepherd dogs and to decrease mature weight
      and increase mature height in Labrador retrievers. Mature weights were recorded
      for 1,333 German shepherd dog offspring and their 69 dams and 17 sires, and 1,081
      Labrador retriever offspring and their 51 dams and 13 sires. Mature heights also
      were recorded for offspring and parents, including 871 German shepherd dogs from
      70 dams and 15 sires, and 793 Labrador retrievers from 40 dams and 13 sires.
      Selecting on mature weight alone produced the highest aggregate genetic-economic
      gain for German shepherd dogs compared with the selection indices with and
      without restrictions, generating a 2.10-kg decrease in mature weight and a
      correlated 0.36-cm decrease in mature height. In Labrador retrievers, selecting
      for mature height alone produced the highest aggregate genetic-economic gain but
      caused an increase in mature weight. Weighting the two traits equally but in the
      opposite direction without restrictions was the only index that produced the
      desired effect of decreasing mature weight and increasing mature height in
      Labrador retrievers. Response to selection for one generation of directional
      selection for a single trait included a 0.50-kg decrease in mature weight for
      German shepherd dogs, a 0.59-kg decrease in mature weight for Labrador
      retrievers, a 0.18-cm decrease in mature height for German shepherd dogs, and a
      0.91-cm increase in mature height for Labrador retrievers. Increasing the
      percentage of dogs attaining optimum size may decrease the cost of production for
      the Seeing Eye, Inc., because fewer dogs would need to be raised and trained to
      provide assistance to the same number of blind individuals.

PMID- 14677850
TI  - Simulation study of teat score in first-parity Gelbvieh cows: parameter
      estimation.
AB  - Teat scores from 9,598 first-parity Gelbvieh cows were used to investigate the
      adequacy of grouping approaches to decrease score misclassifications or
      inconsistencies as well as to simplify the data collection process. The procedure
      was tested using simulated data and then validated using teat score records of
      Gelbvieh cattle. First-parity cows were considered to be 4 yr of age or younger
      at first calving, did not have multiple records within 280 d, and were at least
      50% Gelbvieh. Producers scored cows within 24 h of parturition. Teat score, a
      subjective measure of teat size, ranged from 0 (very large) to 50 (very small). A
      linear mixed model that included herd-year, month of calving, and age at calving
      as systematic effects; regression on the percentage of Gelbvieh; and additive
      breeding values (BV) and residual as random effects was used to generate the
      data. Simulated data were analyzed using one of three scoring methods: all values
      (S50), 10 classes (S10), and five classes (S5). The 10 classes were formed by
      subdividing every five scores into a single class starting at score zero.
      Similarly, the five classes were formed by combining every 10 scores into one
      class. The average Pearson correlations, based on five replicates, between the
      true and estimated BV (systematic effects) were 0.36 (0.85), 0.35 (0.89), and
      0.32 (0.87) using S50, S10, and S5, respectively. Average correlations between
      estimated BV (systematic effects) were 0.97 (0.95), 0.89 (0.92), and 0.92 (0.97)
      based on S50 and S10, S50 and S5, and S10 and S5, respectively. Field data were
      used to validate the simulation procedure. The field data were categorized into
      10 classes (F10) and five classes (F5) as described for the simulated data.
      Pearson correlations between estimated BV (systematic effects) were 0.99 (0.93),
      0.93 (0.88), and 0.93 (0.96), based on F50 with F10, F50 with F5, and F10 with
      F5, respectively. The extremely high correlations between predicted BV based on
      S50, S10, S5, F50, F10, with F5 suggest that a simplified score classification
      method could be adopted without compromising the expected genetic progress for
      the trait under consideration. Furthermore, the difference in corresponding
      Pearson correlations across the field and simulated data might suggest the
      presence of some inconsistencies or misclassifications of the actual scoring
      system.

PMID- 14677851
TI  - Expected increases in genetic merit from using optimized contributions in two
      livestock populations of beef cattle and sheep.
AB  - The expected benefits from optimized selection in real livestock populations were
      evaluated by applying dynamic selection algorithms to two livestock populations
      of sheep (Meatlinc) and beef cattle (Aberdeen Angus). In addition, the effects of
      introducing BLUP evaluations on the population structure, genetic gain, and
      inbreeding were investigated. The use of BLUP-EBV accelerated the rates of gain
      in the Meatlinc, but the effects of BLUP evaluations on Aberdeen Angus are not as
      evident. Although steady increases in the average coefficient of inbreeding (F)
      were observed, the inbreeding rates (deltaF) before and after the introduction of
      BLUP evaluations were not significantly different. The observed deltaF in the
      last generation was 1.0% for Meatlinc and 0.2% for Aberdeen Angus. The
      application of the dynamic selection algorithms for maximizing genetic gain at a
      fixed deltaF led to important expected increases in the rate of genetic gain
      (deltaG). When deltaF was restricted to the value observed in both populations,
      increments per year in deltaG of 4.6 (i.e., 17%) index units for Meatlinc and 3.5
      (i.e., 30%) index units for Aberdeen Angus were found in comparison to the deltaG
      expected from conventional truncation BLUP selection. More relaxed constraints on
      deltaF allowed even higher expected increases in deltaG in both populations. This
      study demonstrates that the optimization tools constitute a potentially highly
      effective way of managing gain and inbreeding under a broad range of schemes in
      terms of scale and inbreeding level. No losses in genetic gain were associated
      with the use of dynamic optimization selection when schemes were compared at the
      same deltaF.

PMID- 14677852
TI  - Detection of quantitative trait loci for growth and carcass composition in
      cattle.
AB  - The objective of the present study was to detect quantitative trait loci for
      economically important traits in a family from a Bos indicus x Bos taurus sire. A
      Brahman x Hereford sire was used to develop a half-sib family (n = 547). The sire
      was mated to Bos taurus cows. Traits analyzed were birth (kg) and weaning weights
      (kg); hot carcass weight (kg); marbling score; longissimus area (cm2); USDA yield
      grade; estimated kidney, pelvic, and heart fat (%); fat thickness (cm); fat yield
      (%); and retail product yield (%). Meat tenderness was measured as Warner
      Bratzler shear force (kg) at 3 and 14 d postmortem. Two hundred and thirty-eight
      markers were genotyped in 185 offspring. One hundred and thirty markers were used
      to genotype the remaining 362 offspring. A total of 312 markers were used in the
      final analysis. Seventy-four markers were common to both groups. Significant QTL
      (expected number of false-positives < 0.05) were observed for birth weight and
      longissimus area on chromosome 5, for longissimus area on chromosome 6, for
      retail product yield on chromosome 9, for birth weight on chromosome 21, and for
      marbling score on chromosome 23. Evidence suggesting (expected number of false
      positives < 1) the presence of QTL was detected for several traits. Putative QTL
      for birth weight were detected on chromosomes 1, 2, and 3, and for weaning weight
      on chromosome 29. For hot carcass weight, QTL were detected on chromosomes 10,
      18, and 29. Four QTL for yield grade were identified on chromosomes 2, 11, 14,
      and 19. Three QTL for fat thickness were detected on chromosomes 2, 3, 7, and 14.
      For marbling score, QTL were identified on chromosomes 3, 10, 14, and 27. Four
      QTL were identified for retail product yield on chromosomes 12, 18, 19, and 29. A
      QTL for estimated kidney, pelvic, and heart fat was detected on chromosome 15,
      and a QTL for meat tenderness measured as Warner-Bratzler shear force at 3 d
      postmortem was identified on chromosome 20. Two QTL were detected for meat
      tenderness measured as Warner-Bratzler shear force at 14 d postmortem on
      chromosomes 20 and 29. These results present a complete scan in all available
      progeny in this family. Regions underlying QTL need to be assessed in other
      populations.

PMID- 14677853
TI  - Risk-adjusted expected return for selection decisions.
AB  - The results of genetic evaluation are predictions of breeding values for the
      selection candidates, and these involve uncertainty with regard to future returns
      from the use of those selected individuals. This uncertainty is due to
      differential variability in BLUP of breeding values and can be translated into
      risk: High fluctuations mean greater risk, which is not taken into account by
      just looking at expected return. In this research, the methodology of value at
      risk (VaR) and expected shortfall is introduced for animal breeding decisions as
      a means to adjust the expected return for the cost of uncertainty in prediction
      of breeding values. This methodology has recently received a great deal of
      attention from financial institutions. Given a specified probability alpha, VaR
      is the alpha-quantile of the distribution of economic returns. The conditional
      value at risk (CVaR), or expected shortfall, is the expectation of the economic
      returns, which are less or equal to the VaR. By subtracting the CVaR from the
      predicted aggregate genotype (muR), a risk-adjusted expected return (RAER)
      measure was obtained. The measures muR, VaR, and RAER were calculated for a data
      set with progeny of 161 Polled Hereford bulls belonging to a beef cattle company.
      The Pearson and Spearman correlations between muR and RAER were 0.89 (P < 0.001)
      and 0.90 (P < 0.001), respectively. Even though the latter correlation was high,
      some bulls ranked differently for muR compared with RAER. The Pearson correlation
      between muR and VaR was low (0.124) and nonsignificant (P > 0.05), whereas the
      correlation between VaR and RAER was -0.31 (P < 0.0001). The results indicate the
      need to take into account the adjustment for risk in expected return in order to
      alleviate the effects of possible losses when overrated animals are selected.

PMID- 14677854
TI  - Postmodernism for animal scientists.
AB  - Many scientists regard the term "postmodernism" as controversial. Because
      postmodern theorists question whether science can be objective, some scientists
      view postmodernism as anti-scientific. In this paper, we argue that traditional
      accounts of science developed during the modern era (16th, 17th, and 18th
      centuries) are still influential in animal science, but are no longer plausible.
      In particular, the view that science automatically leads to human betterment
      seems to be disingenuous. A postmodern view that portrays science as a political
      activity seems more plausible, and offers a means to better understand
      contentious policy issues that involve science. Although most animal scientists
      accept the view that theory selection, experimental designs, and technology
      development require value-laden judgments, most fail to recognize that such
      values may be politically motivated and embrace prevailing political structures.
      Postmodernists such as Michel Foucault argue that through the generation of
      knowledge, scientific disciplines create a discourse that serves to maintain a
      particular social structure that has political implications. Viewed in this way,
      it becomes clear how various interest groups can be critical of certain
      scientific programs. For example, groups that oppose research dealing with
      cloning, genetically modified organisms, and intensive livestock production may
      not be as much opposed to science as they are to the political interests served
      by this science. In other words, such groups view these research agendas as
      promoting policies that place them at risk. Such a postmodern account of science,
      may help animal scientists better understand the nature of contentious issues,
      and provide a basis for reforming the animal science discipline in ways that make
      it more responsive to the diverse interests of a pluralistic society.

PMID- 14677855
TI  - Predicting the consequences of social stressors on pig food intake and
      performance.
AB  - The influence of social stressors on pig performance, although undeniable, is
      frequently underestimated, and in pig growth modeling is generally ignored. The
      aims here were to quantify the effects of the main social stressors (i.e., group
      size, space allowance, feeder space allowance, and mixing) on the performance of
      growing pigs and to incorporate these relationships into a general growth
      simulation model. Effects of the individual stressors were described by
      conceptual equations derived on biological grounds. Parameter values were
      estimated from experimental data, while taking steps to avoid the problems of
      using a strictly empirical approach. It was assumed that social stress decreases
      the capacity of the animal to attain its potential. This is equivalent to
      lowering the maximum rate of daily gain (ADGp, kg/d). Because it is generally
      assumed that animals eat to attain their potential, a decrease in ADGp
      necessarily leads to a decrease in intake. Genetic variation among genotypes in
      their ability to cope with social stressors was accounted for by introducing an
      extra genetic parameter (EX) into the model. The value of EX adjusts both the
      intensity of stressor at which the animal becomes effectively stressed and the
      extent to which stress decreases performance and increases energy expenditure at
      a given stressor intensity. Rather than using an empirical adjustment to predict
      values for the model output variables, such as intake and gain, the chosen
      functional forms were integrated into a general growth model as mechanistic
      equations. This allowed the effects of interactions that exist between social
      stressors and the other variables, such as the genotype, feed composition, and
      environment on pig intake and growth, to be explored and, at least in principle,
      predicted. The adapted model is able to predict the performance of pigs differing
      in both the potential and ability to cope with environmental stressors when
      raised under given dietary, physical, and social environmental conditions. The
      social stressor equations developed here can be incorporated into other pig
      growth simulation models.

PMID- 14677856
TI  - Porcine leptin inhibits lipogenesis in porcine adipocytes.
AB  - The present study examined whether recombinant porcine leptin alters lipid
      synthesis in porcine adipocytes. The stromal-vascular cell fraction of neonatal
      pig subcutaneous adipose tissue was isolated by collagenase digestion,
      filtration, and subsequent centrifugation. These cells were seeded on 25-cm2
      tissue culture flasks and proliferated to confluency in 10% (vol/vol) fetal
      bovine serum in Dulbecco's modified Eagle medium/F12 (DMEM/F12, 50:50). Cultures
      were differentiated using 2.5% pig serum (vol/vol), 10 nM insulin, 100 nM
      hydrocortisone. After 7 d of lipid filling, cultures were washed free of this
      medium, incubated overnight in DMEM/F12 containing 2% pig serum (vol/vol), and
      then used for experiments. Acute experiments assessed U-(14)C-glucose or 1-(14)C
      palmitate metabolism in cultures exposed to porcine leptin (0 to 1,000 ng/mL
      medium) for 4 h. Chronic experiments used cultures incubated with 0 to 1,000 ng
      porcine leptin/mL medium for 44 h before measurements of U-(14)C-glucose and 1
      (14)C-palmitate oxidation and incorporation into lipid. Another experiment
      examined whether chronic leptin treatment alters insulin responsiveness by
      including insulin (10 nM) with incubations containing leptin. Leptin had no acute
      effects on glucose oxidation or conversion to lipid (P > 0.05). Acute leptin
      treatment decreased palmitate incorporation into lipids up to 45% (P < 0.05).
      Chronic leptin exposure decreased glucose oxidation (21%), total lipid synthesis
      (18%), and fatty acid synthesis (23%) at 100 ng/mL medium (P < 0.05). Insulin
      increased rates of glucose oxidation, total lipid, and fatty acid synthesis (P <
      0.05); however, chronic exposure to 10 ng leptin/mL medium decreased the
      effectiveness of 10 nM insulin to affect these measures of glucose metabolism by
      approximately 18 to 46% (P < 0.05). Higher concentrations of leptin inhibited all
      effects of insulin on glucose metabolism (P < 0.05). Chronic exposure to leptin
      increased palmitate oxidation by 36% (P < 0.05). Chronic leptin exposure
      decreased palmitate incorporation into total lipids by 40% at 100 ng/mL medium (P
      < 0.05). Lipoprotein lipase activity was not affected (P > 0.05) by leptin. These
      data indicate that leptin functions to promote partitioning of energy away from
      lipid accretion within porcine adipose tissue by inhibiting glucose oxidation and
      lipogenesis indirectly, by decreasing insulin-mediated stimulation of
      lipogenesis, and by stimulating fatty acid oxidation while inhibiting fatty acid
      esterification.

PMID- 14677857
TI  - Increased maternal nutrition of sows has no beneficial effects on muscle fiber
      number or postnatal growth and has no impact on the meat quality of the
      offspring.
AB  - The objective of this study was to examine how increased feed intake of the sow
      during early to mid-gestation affects sow performance and the muscle fiber
      number, performance, and technological meat quality of the offspring. Thirty-nine
      pregnant sows (Landrace x Large White sows mated to Landrace or Large White
      boars) in their fourth parity were assigned to one of three treatments: 1) the
      sows were either fed restrictively (control = 15 MJ of NE/d from d 1 to 90, then
      24 MJ of NE/d from d 91 to 112, and again 15 MJ of NE/d from d 113 to 115 of
      gestation); 2) fed ad libitum from d 25 to 50 (A25-50); or 3) ad libitum from d
      25 to 70 (A25-70) and as control in the remaining periods. The offspring were
      weaned at 4 wk of age and had free access to feed from 2 wk of age until
      slaughter. They were slaughtered litterwise at an average body weight of 104 +/-
      14 kg. Estimates for total, primary (P-), and secondary (S-) muscle fiber number;
      muscle fiber area; and DNA and RNA content were analyzed in semitendinosus muscle
      (ST) samples from the heaviest, middle, and lightest weight (LW) pigs of each sex
      within litter selected at slaughter. Technological meat quality traits (pH at 24
      h postmortem, drip loss, Minolta color, and pigment) were analyzed in longissimus
      dorsi muscle. Fiber number, fiber area, and concentrations and content of DNA and
      RNA of the offspring were not significantly affected by increased maternal
      nutrition. The ST muscle weight was lower in offspring from A25-50 than control
      sows (P = 0.019). Average daily gain, carcass weight, and the muscle deposition
      rate also were numerically lower for A25-50 than control and A25-70 pigs. An
      interaction between treatment and pig weight was found for muscle deposition rate
      (P = 0.006), in that LW pigs from treatment A25-50 had a lower deposition rate
      than LW pigs from control. We found no effect of treatment on the meat quality
      traits in the offspring. Also, barrows had a higher (P < 0.05) number of P
      fibers, higher daily gain, and carcass weight than female pigs. No differences
      were found on any meat quality traits between sexes. Thus, ad libitum feeding of
      pregnant sows from d 25 to 50 or d 25 to 70 of gestation did not have any
      beneficial effect on muscle fiber number and area in the offspring. It seems that
      maternal ad libitum feeding from d 25 to 50 in gestation had a negative effect on
      postnatal muscle growth, with especially the LW pigs being affected.

PMID- 14677858
TI  - Effects of flax supplementation and a combined trenbolone acetate and estradiol
      implant on circulating insulin-like growth factor-I and muscle insulin-like
      growth factor-I messenger RNA levels in beef cattle.
AB  - We evaluated effects of a 5% (dry matter basis) ground flaxseed supplement (flax)
      and a trenbolone acetate and estradiol-17beta implant, Revalor-S, on circulating
      IGF-I and muscle IGF-I messenger RNA (mRNA). Sixteen crossbred yearling steers
      (initial BW = 397 kg) were assigned randomly to one of four treatments: 1)
      flax/implant; 2) nonflax/implant; 3) flax/nonimplant; and 4) nonflax/nonimplant.
      Serum was harvested from blood collected on d 0 (before implant or flax
      addition), 14, and 28, and used in subsequent analyses of circulating IGF-I.
      Biopsy samples (0.5 g) were obtained from the longissimus muscle on d 0, 14, and
      28. Total RNA was isolated from the muscle samples, and real-time quantitative
      PCR was used to assess relative differences in IGF-I mRNA. Flax supplementation
      had no effect (P > 0.10) on circulating IGF-I concentrations. Following
      implantation, sera from implanted steers had 52 and 84% greater (P < 0.05) IGF-I
      concentrations than sera from nonimplanted steers on d 14 and 28, respectively.
      On d 28, local muscle IGF-I mRNA levels increased 2.4-fold (P < 0.01) in biopsy
      samples obtained from implanted compared with nonimplanted steers. Muscle biopsy
      samples from nonflax cattle had 4.4-fold higher (P < 0.01) levels of IGF-I mRNA
      than those from flax cattle on d 28. To determine whether a component of flax,
      alpha-linolenic acid (alphaLA), was directly responsible for IGF-I mRNA down
      regulation, we incubated primary cultures of bovine satellite cells, from
      implanted and nonimplanted steers, in two concentrations of alphaLA (10 nM and 1
      microM). An implant x dose interaction (P < 0.05) was observed for IGF-I mRNA
      concentrations in bovine satellite cells cultured for 72 h with alphaLA.
      Satellite cells from nonimplanted steers had similar (P > 0.10) IGF-I mRNA
      concentration regardless of the level of alphaLA exposure; however, satellite
      cells from implanted steers exposed to 10 nM and 1 microM alphaLA had 2.5- and
      2.0-fold greater IGF-I mRNA levels, respectively, than cells from implanted
      steers that were not exposed to alphaLA (P < 0.05). Administration of a Revalor-S
      implant increased circulating IGF-I and local muscle IGF-I mRNA concentrations in
      finishing cattle. However, muscle IGF-I mRNA levels were decreased by flax
      supplementation. Muscle cell culture experiments suggested that alphaLA was not
      responsible for the IGF-I mRNA down-regulation.

PMID- 14677859
TI  - Molecular ecological analysis of porcine ileal microbiota responses to
      antimicrobial growth promoters.
AB  - Cultivation-independent microbial molecular ecology approaches were used to
      examine the effects of antibiotic growth promoters on the pig ileal microbiota.
      Five-week-old barrows were fitted with a simple T-cannula at the distal ileum.
      Three diets meeting or exceeding the minimum nutrient requirements were fed for 5
      wk and supplemented as follows: 1) negative control (no antibiotic; n = 5), 2)
      continuous tylosin administration (n = 5), and 3) an antibiotic rotation sequence
      (wk 1, chlorotetracycline sulfathiazole penicillin; wk 2, bacitracin and
      roxarsone; wk 3, lincomycin; wk 4, carbadox; wk 5, virginiamycin; n = 5). Ileal
      luminal contents were collected for DNA isolation at the end of each of the 5 wk
      of the testing period. The V3 region of 16S rDNA was amplified by PCR and
      analyzed via denaturing gradient gel electrophoresis (DGGE) and quantitative
      polymerase chain reaction (qPCR). Resulting PCR-DGGE band numbers (bacterial
      species) were counted, and the banding patterns analyzed by calculating
      Sorenson's pairwise similarity coefficients (C(S)), an index measuring bacterial
      species in common among samples. Band numbers and total bacterial DNA
      concentrations decreased (P < 0.05) temporally in antibiotic-treated pigs
      compared with controls. Comparisons between treatments yielded low intertreatment
      C(S) indices, indicating treatment-dependent alterations in banding patterns,
      whereas intratreatment comparisons revealed increased homogeneity in antibiotic
      treated vs. control pigs. Sequence analysis of treatment-specific bands
      identified three Lactobacillus, one Streptococcus, and one Bacillus species that
      were diminished with antibiotic rotation treatment, whereas tylosin selected for
      the presence of L. gasseri. Lactobacillus-specific qPCR was performed and
      analyzed as a percentage of total bacteria to further evaluate the effects of
      antibiotic administration on this genus. Total bacteria were decreased (P < 0.05)
      by tylosin and rotation treatments, whereas the percentage of lactobacilli
      increased (P < 0.05) by d 14 and through d 28 in tylosin-treated pigs. The
      decrease in total bacteria by antibiotics may reduce host-related intestinal or
      immune responses, which would divert energy that could otherwise be used for
      growth. Conversely, the ability of tylosin to improve animal growth may relate to
      its apparent selection for lactobacilli, commensals known to competitively
      exclude potentially pathogenic species from colonizing the intestine.

PMID- 14677860
TI  - Porcine leptin inhibits protein breakdown and stimulates fatty acid oxidation in
      C2C12 myotubes.
AB  - This study evaluated the potential mechanism(s) by which leptin treatment
      inhibits loss of muscle mass with fasting. Cultures of C2C12 myoblasts were
      differentiated into myotubes with 5% (vol/vol) horse serum in Dulbecco's modified
      Eagle's medium/F12. These myotubes were used to assess 3H-tyrosine incorporation
      and release following incubation with recombinant porcine leptin (0 to 500
      ng/mL). Protein synthesis in myotubes, as measured by 3H-tyrosine incorporation,
      was not affected by leptin treatment (P > 0.05). Protein breakdown in C2C12
      myotubes, as measured by 3H-tyrosine release, was inhibited by leptin treatment.
      A leptin concentration of 0.5 ng/mL was sufficient to inhibit 3H-tyrosine release
      by 3.5% (P < 0.05); 50 ng/mL produced a maximal inhibition of 10.2% (P < 0.05).
      Dexamethasone (1 microM) was used to maximally stimulate protein breakdown.
      Leptin (50 ng/mL leptin) decreased dexamethasone-induced 3H-tyrosine release by
      32% (P < 0.05). The inhibition of 3H-tyrosine release in C2C12 myotubes suggests
      that leptin produces a protein-sparing effect in vitro by inhibiting protein
      breakdown. Fatty acid metabolism also was investigated because fatty acids are a
      major energy source for muscle during periods of reduced intake, as occurs with
      leptin treatment. Acute (4 h) and chronic (24 h) exposures to porcine leptin (0
      to 500 ng/mL) were used to evaluate 14C-palmitate oxidation. Acute leptin
      treatment had no effect (P > 0.05) on palmitate metabolism. Chronic leptin
      exposure resulted in up to a 26% increase in palmitate oxidation (P < 0.05). The
      stimulation of fatty acid oxidation with chronic leptin treatment suggests that
      leptin spares other energy sources in muscle from oxidation during periods of a
      leptin-induced decrease in feed intake.

PMID- 14677861
TI  - Effects of growth implants on consumer perceptions of meat tenderness in beef
      steers.
AB  - Anabolic steroid implants are routinely used to increase growth performance and
      profitability; however, there are concerns that the use of implants, particularly
      those containing trenbolone acetate, may have detrimental effects on carcass
      quality and beef tenderness. Thus, the objectives of the current study were to
      determine the effects of various commonly used implant regimens on shear force
      values, sensory properties, and consumer satisfaction of beef top loin steaks
      from cattle of Bos indicus influence. Cattle were supplied by producers that
      agreed to provide sire and dam information in exchange for carcass and sensory
      data. Steers (n = 2,748) were assigned randomly to one of three implant
      treatments (12/sire; four steers from each sire were placed into each treatment
      group): 1) unimplanted controls (n = 1,368); 2) Synovex-S followed by another
      Synovex-S (n = 660); or 3) Synovex-S followed by Revalor-S (n = 720). Steaks
      sampled after 3, 7, and 14 d of aging indicated that unimplanted cattle had lower
      (P < 0.05) Warner-Bratzler Shear force values than those from implanted animals.
      No differences (P > 0.05) in shear force values were found between the two
      treatments or the control groups for steaks sampled following a 21-d aging
      period. Steaks from implanted animals sampled after 3, 7, and 14 d aging were
      rated lower (P < 0.05) for initial and sustained trained sensory panel tenderness
      scores. Consumers failed to detect any differences in steak samples related to
      implant treatment after 7 and 14 d of aging. Consumer education level and family
      income did not affect overall acceptability (P > 0.10 and 0.18, respectively) or
      tenderness acceptability (P > 0.11 and 0.68, respectively); however, consumers
      with postgraduate degrees recorded lower (P < 0.05) overall quality, beef flavor,
      juiciness, and tenderness scores than consumers in all other education
      classifications. Additionally, family income had no effect on overall quality (P
      > 0.21), beef flavor (P > 0.28), juiciness (P > 0.58), or tenderness (P > 0.45)
      scores. Results indicate that using a moderate implant program in Bos indicus
      influenced cattle has no detrimental effects on beef tenderness and consumer
      acceptability.

PMID- 14677862
TI  - A dose-response experiment evaluating the effects of oligofructose and inulin on
      nutrient digestibility, stool quality, and fecal protein catabolites in healthy
      adult dogs.
AB  - In this experiment, three concentrations (0.3, 0.6, and 0.9% of diet, as-fed
      basis) of two fructans, oligofructose (OF) and inulin, were tested against a 0%
      supplemental fructan control. Seven ileal-cannulated adult female dogs were fed a
      meat-based, kibbled diet and assigned to treatments in a 7 x 7 Latin square
      design. Dietary supplementation of fructans had no effect on nutrient intakes or
      ileal digestibilities. Total-tract digestibilities of DM, OM, and CP decreased (P
      < 0.05) as a result of dietary OF and inulin supplementation. Dogs fed the
      control diet had a DM total-tract digestibility of 83.0%. The percentages of
      fecal DM for dogs fed the control and 0.3, 0.6, and 0.9% OF were 36.6, 33.3,
      32.8, and 31.7%, respectively. When compared with the control, OF (P < 0.01) and
      inulin (P < 0.01) supplementation increased fecal ammonia concentrations. Higher
      fecal short-chain fatty acid (SCFA; P < 0.10) and isovalerate concentrations (P <
      0.01) were noted for dogs fed both fructans. Total fecal SCFA for dogs fed the
      control diet and 0.3, 0.6, and 0.9% OF were 406.4, 529.9, 538.3, and 568.8
      micromol/g of feces (DM basis), respectively. Dogs fed 0.3, 0.6, and 0.9% inulin
      had total fecal SCFA of 472.2, 468.8, and 471.5 micromol/g of feces (DM basis),
      respectively. Linear increases were observed in putrescine (P < 0.11), cadaverine
      (P < 0.07), spermidine (P < 0.12), and total amines (P < 0.05) in feces of dogs
      fed OF. Lower fecal phenol (P < 0.08) and total phenol (P < 0.04) concentrations
      occurred in dogs fed inulin, along with a linear decrease (P < 0.08) in total
      phenols with OF supplementation. Total fecal phenols for dogs fed the control,
      0.3, 0.6, and 0.9% inulin were 3.03, 1.86, 1.97, and 2.23 micromol/g of feces (DM
      basis), respectively. Low-level dietary inclusion of inulin and OF positively
      affected indices known to be associated with gut health of the dog without
      seriously compromising nutrient digestibility or stool quality. Overall, the 0.9%
      OF treatment resulted in the best responses, including no adverse effect on
      nutrient intakes, ileal digestibilities, or stool quality, as well as increased
      fecal SCFA and decreased fecal phenols. The biological responses due to inulin
      were more variable.

PMID- 14677863
TI  - Effects of dietary electrolyte balance on the chemistry of blood and urine in
      lactating sows and sow litter performance.
AB  - One hundred fifty-three sows (average parity of 2.2) were used to determine the
      effects of dietary electrolyte balance (calculated as mEq/kg of diet for Na + K -
      Cl) on sows and their litters during lactation. The sows were fed corn-soybean
      meal-based diets (1.0% lysine, 1.0% valine, 0.95% Ca, and 0.80% P; as-fed basis)
      starting on d 109 of gestation and throughout the 21-d lactation experiment.
      Dietary electrolyte balance (dEB) was 0, 100, 200, 350, and 500 mEq/kg (as-fed
      basis), well above and below the dEB of 185 mEq/kg found in a simple corn-soybean
      meal-based lactation diet. To achieve the desired dEB, diets had the following:
      1) 1.8% HCl (6 N) and 1.06% CaCl2, 2) 1.0% CaCl2, 3) 0.04% NaHCO3, 4) 1.29%
      NaHCO3, and 5) 2.54% NaHCO3 (as-fed basis). Increasing dEB increased blood pH
      (linear and quadratic effects, P < 0.001), partial pressure of carbon dioxide
      (linear effect, P < 0.001), HCO3- concentration (linear and quadratic effects, P
      < 0.001), and blood base excess (linear and quadratic effects, P < 0.001).
      However, increased dEB resulted in lower blood concentrations of K (linear and
      quadratic effects, P < 0.04), Cl (linear and quadratic effects, P < 0.001), and
      ionized Ca (linear and quadratic effects, P < 0.001). Changing dEB did not affect
      ADFI; water usage, litter weight gain; sow weight change; sow backfat change;
      percentages of CP, lactose, and fat in the milk; percentage of sows returning to
      estrus; days to estrus; and number of pigs born alive in the subsequent litter (P
      = 0.06). However, piglet survivability to d 10 and overall was greatest with the
      lower dEB treatments (linear effect, P < 0.05). The pH (linear and quadratic
      effects, P < 0.001) and colony forming units of total bacteria (linear effect, P
      < 0.03) in the urine increased as dEB of the diet was increased. In conclusion,
      dEB had pronounced effects on the physiological status of sows and decreasing dEB
      below that in a simple corn-soybean meal-based diet decreased bacterial counts in
      the urine and increased piglet survivability. However, milk composition, sow and
      litter weights at weaning, and subsequent rebreeding performance of the sows were
      not affected by dEB.

PMID- 14677864
TI  - Influence of dietary protein level, amino acid supplementation, and dietary
      energy levels on growing-finishing pig performance and carcass composition.
AB  - Two experiments were conducted to determine the effects of feeding reduced-CP, AA
      supplemented diets at two ambient temperatures (Exp. 1) or three levels of
      dietary NE (Exp. 2) on pig performance and carcass composition. In Exp. 1, 240
      mixed-sex pigs were used to test whether projected differences in heat increment
      associated with diet composition affect pig performance. There were 10
      replications of each treatment with four pigs per pen. For the 28-d trial,
      average initial and final BW were 28.7 kg and 47.5 kg, respectively. Pigs were
      maintained in a thermoneutral (23 degrees C) or heat-stressed (33 degrees C)
      environment and fed a 16% CP diet, a 12% CP diet, or a 12% CP diet supplemented
      with crystalline Lys, Trp, and Thr (on an as-fed basis). Pigs gained at similar
      rates when fed the 16% CP diet or the 12% CP diet supplemented with Lys, Trp, and
      Thr (P > 0.10). Pigs fed the 12% CP, AA-supplemented diet had a gain:feed similar
      to pigs fed the 16% CP diet when housed in the 23 degrees C environment but had a
      lower gain:feed in the 33 degrees C environment (diet x temperature, P < 0.01).
      In Exp. 2, 702 gilts were allotted to six treatments with nine replicates per
      treatment. Average initial and final BW were 25.3 and 109.7 kg, respectively.
      Gilts were fed two levels of CP (high CP with minimal crystalline AA
      supplementation or low CP with supplementation of Lys, Trp, Thr, and Met) and
      three levels of NE (high, medium, or low) in a 2 x 3 factorial arrangement. A
      four-phase feeding program was used, with diets containing apparent digestible
      Lys levels of 0.96, 0.75, 0.60, and 0.48% switched at a pig BW of 41.0, 58.8, and
      82.3 kg, respectively. Pigs fed the low-CP, AA-supplemented diets had rates of
      growth and feed intake similar to pigs fed the high-CP diets. Dietary NE
      interacted with CP level for gain:feed (P < 0.06). A decrease in dietary NE from
      the highest NE level decreased gain:feed in pigs fed the high-CP diet; however,
      gain:feed declined in pigs fed the low-CP, AA-supplemented diet only when dietary
      NE was decreased to the lowest level. There was a slight reduction in longissimus
      area in pigs fed the low-CP diets (P < 0.08), but other estimates of carcass
      muscle did not differ (P > 0.10). These data suggest that pigs fed low-CP, AA
      supplemented diets have performance and carcass characteristics similar to pigs
      fed higher levels of CP and that alterations in dietary NE do not have a
      discernible effect on pig performance or carcass composition.

PMID- 14677865
TI  - The role of acidogenic diets and beta-hydroxybutyate on lymphocyte proliferation
      and serum antibody response against bovine respiratory viruses in Holstein
      steers.
AB  - Acidogenic diets were evaluated for their effects on lymphocyte proliferation in
      response to Staphylococcus aureus exotoxin B (SEB), and specific lymphocyte
      proliferation and serum-neutralizing antibody titers to four bovine respiratory
      viruses in vitro. Four Holstein steer calves, with an average weight of 213 +/-
      42 kg, were fed a basal (control) diet consisting of 49% forage and 51%
      concentrate (DM basis), with 15% CP (on a DM basis). Three additional treatment
      diets were used: 1) the basal diet supplemented with 700 mL/d of butylene glycol
      (BG) to induce ketoacidosis by increasing blood beta-hydroxybutyate (BHBA); 2)
      the basal diet supplemented with 1.2 +/- 0.1 kg/d of anionic salts (AS; Soychor
      16.7, West Central Soy, Ralston, IA) to induce a metabolic acidosis; and 3) the
      basal diet with all forage replaced by finely ground corn and soybean meal
      blended to provide 15% CP (HG), to induce lactic acidosis. The calves were fed
      each diet for 21 d in a 4 x 4 Latin square design. Blood samples were collected
      on d 18, 19, and 20 of each 21-d period and analyzed for pH; concentrations of
      BHBA; in vitro lymphocyte proliferation to SEB, bovine viral diarrhea virus
      (BVDV), bovine respiratory syncytial virus (BRSV), parainfluenza-3 (PI-3), and
      bovine herpesvirus-1 (BHV-1); and titers of serum-neutralizing antibodies against
      the four viruses. Following treatment, the average pH of the serum samples was
      7.38 for calves fed the control diet, 7.37 for the BG treatment, and 7.36 for the
      HG treatment, and was decreased (P < 0.05) to 7.33 for the AS treatment. All
      acidogenic diets decreased lymphocyte response to SEB (P < 0.05). The lymphocyte
      proliferative response, however, of each virus showed a different pattern of
      interaction with the three acidogenic diets tested. The AS diet was associated
      with increased lymphocyte proliferative response to BVDV and BRSV (P < 0.01) and
      increased serum neutralization titers to BHV-1 (P < 0.05). In calves fed the BHBA
      inducing diet (BG), an increase in lymphocyte proliferation to BRSV was observed
      (P < 0.05). A similar relationship to blood BHBA concentration was not observed
      with the lymphocyte proliferation to BVDV, PI-3, or BHV-1. Titers of serum
      neutralizing antibody against PI3 (P < 0.05) and BHV-1 (P < 0.01) were negatively
      correlated with blood pH, and titers of serum neutralizing antibodies to BHV-1
      were negatively correlated to elevated circulating concentrations of BHBA (P <
      0.05).

PMID- 14677866
TI  - Dexamethasone and colostrum feeding affect hepatic gluconeogenic enzymes
      differently in neonatal calves.
AB  - Plasma glucose concentrations in neonates are influenced by colostrum feeding and
      by glucocorticoids. We have tested whether a high-glucocorticoid status after
      birth, as well as colostrum feeding, influences glucose metabolism in association
      with changes of hepatic expression and activities of gluconeogenic enzymes
      phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) and pyruvate carboxylase
      (PC; EC 6.4.1.1) in neonatal calves. Calves (n = 14 per group) were fed either
      colostrum or a milk-based formula with nutrient and energy contents similar to
      colostrum. Half the calves in each feeding group were treated with dexamethasone
      (DEXA; 30 microg/[kg BW x d]). Pre- and postprandial blood samples were taken on
      d 1, 2, 4, and 5 and liver samples were collected on d 5 of life. Dexamethasone
      treatment increased (P < or = 0.05) plasma concentrations of glucose, insulin,
      and glucagon more in colostrum-fed than in formula-fed calves but increased (P <
      or = 0.05) urea concentrations and decreased (P < or = 0.05) concentrations of
      NEFA, ACTH, and cortisol independent of colostrum vs. formula feeding. Colostrum
      feeding increased (P < 0.05) plasma glucose, but decreased (P < 0.05) plasma urea
      concentrations. Glucagon-to-insulin ratios in DEXA-treated and colostrum-fed
      calves were decreased (P < 0.05). Dexamethasone treatment decreased hepatic mRNA
      levels and activities of PC (P < 0.001 and P < 0.10) and activities of PEPCK (P <
      0.001) but increased (P < 0.001) the glycogen content. Colostrum feeding
      increased (P < 0.05) mitochondrial PEPCK mRNA levels and PEPCK activities in
      calves not treated with DEXA but decreased (P < 0.1) amounts of PC mRNA. In
      conclusion, increased plasma glucose concentrations after DEXA treatment were not
      associated with a stimulation of hepatic gluconeogenic enzyme activities;
      however, colostrum feeding probably raised plasma glucose concentrations because
      of increased hepatic gluconeogenic activities.

PMID- 14677867
TI  - Influence of body condition at calving and postpartum nutrition on endocrine
      function and reproductive performance of primiparous beef cows.
AB  - The influences of body condition score (BCS) at calving and postpartum nutrition
      on endocrine and ovarian functions, and reproductive performance, were determined
      by randomly allocating thin (mean BCS = 4.4 +/- 0.1) or moderate condition (mean
      BCS = 5.1 +/- 0.1) Angus x Hereford primiparous cows to receive one of two
      nutritional treatments after calving. Cows were fed to gain either 0.45 kg/d (M,
      n = 17) or 0.90 kg/d (H, n = 17) for the first 71 +/- 3 d postpartum. All cows
      were then fed the M diet until 21 d after the first estrus. A replication (yr 2;
      M, n = 25; H, n = 23) was also used to evaluate reproductive characteristics.
      Concentrations of IGF-I, leptin, insulin, glucose, NEFA, and thyroxine were
      quantified in plasma samples collected weekly during treatment and during 7 wk
      before the first estrus. Estrous behavior was detected by radiotelemetry, and
      luteal activity was determined based on concentrations of progesterone in plasma.
      All cows were bred by AI between 14 and 20 h after onset of estrus, and pregnancy
      was assessed at 35 to 55 d after AI by ultrasonography. Cows that calved with a
      BCS of 4 or 5 had similar endocrine function and reproductive performance at the
      first estrus. During treatment, H cows gained BW and increased BCS (P < 0.01),
      and had greater (P < 0.05) concentrations of IGF-I, leptin, insulin, glucose, and
      thyroxine in plasma than M cows. However, during the 7 wk before the first
      estrus, plasma concentrations of IGF-I, leptin, insulin, glucose, NEFA, and
      thyroxine were not affected by time. Cows previously on the H treatment had a
      shorter (P < 0.01) interval to first postpartum estrus and ovulation, and a
      larger dominant follicle (P < 0.01) at first estrus, than M cows, but duration of
      estrus and the number of mounts received were not influenced by nutrient intake.
      Pregnancy rate at the first estrus was greater (P < 0.03) for H (76%, n = 38)
      than for M (58%, n = 33) cows. Increased nutrient intake after calving stimulated
      secretion of anabolic hormones, promoted fat deposition, shortened the postpartum
      interval to estrus, and increased pregnancy rate at the first estrus.
      Concentrations of IGF-I and leptin in plasma were constant during 7 wk before the
      first estrus, indicating that acute changes in these hormones are not associated
      with the resumption of ovarian function in primiparous beef cows.

PMID- 14677868
TI  - Wet corn gluten feed and alfalfa hay combinations in steam-flaked corn finishing
      cattle diets.
AB  - One finishing trial and one digestibility trial were used to evaluate wet corn
      gluten feed (WCGF) and alfalfa hay (AH) combinations in steam-flaked corn (SFC)
      finishing diets. In Exp. 1, 631 crossbred heifers (initial BW = 284 +/- 7.9 kg)
      were fed SFC-based diets containing combinations of WCGF (25, 35, or 45% of diet
      DM) and AH (2 or 6% of dietary DM) in a 2 x 3 factorial arrangement of
      treatments. No interactions existed between WCGF and AH for heifer performance.
      Increasing dietary WCGF linearly decreased gain efficiency (P < 0.01), dietary
      NEg concentration (P < 0.05), and 12th-rib fat thickness (P = 0.10). Cattle fed
      35% WCGF had the lowest occurrence of abscessed livers, resulting in a quadratic
      response (P < 0.05) as dietary WCGF increased. In Exp. 2, 12 ruminally cannulated
      Jersey steers (585 kg) were fed SFC-based diets containing combinations of WCGF
      (25 or 45% of diet DM) and AH (0, 2, or 6% of diet DM) in an incomplete Latin
      square design with a 2 x 3 factorial arrangement of treatments. Starch intake was
      lower (P < 0.05), but NDF intake was greater (P < 0.05) as AH and WCGF increased
      in the diet. Ruminal pH was increased by AH (linear, P < 0.05) and tended (P <
      0.07) to increase with WCGF. Feeding 2% AH led to the greatest ruminal NH3 but
      the lowest total VFA and propionate (quadratic, P < 0.05). Addition of AH to
      diets containing 25% WCGF increased acetate to a greater extent than addition to
      diets containing 45% WCGF (AH x WCGF interaction, P < 0.05). Feeding 45% WCGF
      tended to increase passage rate (P = 0.17) and decrease (P < 0.05) total tract OM
      digestibility but increase (P < 0.05) in situ degradation of DM from AH and WCGF.
      Interactions between AH and WCGF existed (P < 0.05) for ruminal fluid volume
      (quadratic effect of AH x WCGF level), in situ SFC degradation (linear effect of
      AH x WCGF level), and in situ rate of WCGF DM disappearance (quadratic effect of
      AH x WCGF level). We conclude that AH levels may be decreased when WCGF is added
      to SFC diets as 25% or more of the dietary DM.

PMID- 14677869
TI  - Effect of the live weight gain of steers during winter grazing on digestibility,
      acid-base balance, blood flow, and oxygen consumption by splanchnic tissues
      during adaptation and subsequent feeding of a high-grain diet.
AB  - Ten multicatherized steers were used in a completely random design to determine
      the effect of previous BW gain on blood flow, acid-base balance, and oxygen
      consumption across portal-drained viscera and liver of growing beef steers fed a
      high-grain diet. Treatments were high (1.31 +/- 0.09 kg/d) or low (0.68 +/- 0.07
      kg/d) daily BW gain during an 82-d winter wheat pasture grazing period and a
      subsequent 37-d transition period. Blood flow, blood gas measurements, and oxygen
      consumption were determined on d 0, 14, 28, 42, and 64 of a high-grain finishing
      period. Compensatory growth was evident in low-gain steers; ADG (1.50 vs. 1.11
      kg/d, P < 0.05) and gain efficiency (0.221 vs. 0.109 kg/kg, P < 0.01) were
      greater from d 14 through 28 than for high-gain steers. Arterial base tended (P <
      0.12) to be greater in low-gain than in high-gain steers, whereas calculated HCO3
      (mmol/L; P < 0.20) did not differ between treatments. Arterial O2 concentration
      was not different (P < 0.97) between treatments but increased (P < 0.001) with
      increasing days on feed. Portal blood flow increased with days on feed (P <
      0.001) but did not differ (P < 0.34) between treatments. Hepatic blood flow
      scaled to metabolic BW was 19.7% greater (P < 0.02) in low-gain than in high-gain
      steers. Across the feeding period, O2 consumption and CO2 flux by PDV, liver, and
      total splanchnic tissue (TST) did not differ (P < 0.33) between treatments.
      However, TST O2 consumption (mmol/[h x kg BW(0.75)]) tended (P < 0.12) to be
      greater in low- than in high-gain steers. Compensating steers' arterial blood
      acid-base measurements did not change with days on feed, indicating that they
      were not more susceptible to metabolic acidosis than high-gain steers. However,
      steers that had lower BW gain before high-grain feeding exhibited increased
      hepatic blood flow and TST O2 consumption (metabolic BW basis) during the
      finishing period compared with high-gain steers. Greater hepatic blood flow and
      energy expenditure by TST of previously restricted steers might have facilitated
      compensatory growth.

PMID- 14677870
TI  - Alternative approaches to predicting methane emissions from dairy cows.
AB  - Previous attempts to apply statistical models, which correlate nutrient intake
      with methane production, have been of limited value where predictions are
      obtained for nutrient intakes and diet types outside those used in model
      construction. Dynamic mechanistic models have proved more suitable for
      extrapolation, but they remain computationally expensive and are not applied
      easily in practical situations. The first objective of this research focused on
      employing conventional techniques to generate statistical models of methane
      production appropriate to United Kingdom dairy systems. The second objective was
      to evaluate these models and a model published previously using both United
      Kingdom and North American data sets. Thirdly, nonlinear models were considered
      as alternatives to the conventional linear regressions. The United Kingdom
      calorimetry data used to construct the linear models also were used to develop
      the three nonlinear alternatives that were all of modified Mitscherlich
      (monomolecular) form. Of the linear models tested, an equation from the
      literature proved most reliable across the full range of evaluation data (root
      mean square prediction error = 21.3%). However, the Mitscherlich models
      demonstrated the greatest degree of adaptability across diet types and intake
      level. The most successful model for simulating the independent data was a
      modified Mitscherlich equation with the steepness parameter set to represent
      dietary starch-to-ADF ratio (root mean square prediction error = 20.6%). However,
      when such data were unavailable, simpler Mitscherlich forms relating dry matter
      or metabolizable energy intake to methane production remained better alternatives
      relative to their linear counterparts.

PMID- 14677871
TI  - Influence of dietary cobalt source and concentration on performance, vitamin B12
      status, and ruminal and plasma metabolites in growing and finishing steers.
AB  - Sixty Angus steers, averaging 274 kg, were used to evaluate the effects of Co
      source and concentration on performance, vitamin B12 status, and metabolic
      characteristics of steers. Treatments consisted of 0 (control, analyzed 0.04 mg
      Co/kg), 0.05, 0.10, and 1.0 mg of supplemental Co/kg of DM from CoCO3 or 0.05 and
      0.10 mg of supplemental Co/kg of DM from Co propionate. Steers were individually
      fed a growing diet for 56 d followed by a high-concentrate finishing diet.
      Performance was not affected by Co supplementation during the growing phase.
      During the finishing phase, ADFI (DM basis) and ADG were higher (P < 0.05) for
      the entire finishing phase, and gain:feed was higher (P < 0.10) over the first 56
      d for Co-supplemented steers. Steers supplemented with 0.10 mg Co/kg as Co
      propionate had higher (P < 0.05) ruminal propionate and lower (P < 0.05) acetate
      molar proportions than steers receiving 0.10 Co/kg as CoCO3 during the growing
      phase. Supplemental Co increased (P < 0.10) molar proportion of propionate during
      the finishing phase. Plasma vitamin B12 was higher (P < 0.05) in Co-supplemented
      steers by d 56 of the growing phase and remained higher (P < 0.10) throughout the
      study. Control steers had higher (P < 0.05) plasma methylmalonic acid on d 56 of
      the growing phase and on d 28, 56, and 112 of the finishing phase than steers
      receiving supplemental Co. Steers supplemented with Co had higher plasma glucose
      at d 56 (P < 0.01), 84 (P < 0.10), and 112 (P < 0.01) of the finishing phase.
      Steers supplemented with 0.10 mg Co/kg as Co propionate had higher plasma glucose
      than those receiving 0.10 mg Co/kg as CoCO3 at d 28 of the growing phase (P <
      0.05) and d 28 of the finishing phase (P < 0.10). Final body weight and hot
      carcass weight were lower (P < 0.10) in steers receiving the control diet,
      whereas other carcass characteristics were not affected by dietary Co. Average
      daily gain and feed efficiency for the entire finishing phase did not differ
      among Co-supplemented steers. However, increasing supplemental Co above 0.05
      mg/kg DM (total diet Co = 0.09 mg/kg) resulted in increased (P < 0.01) plasma
      (linear) and liver (quadratic) vitamin B12 concentrations and decreased
      (quadratic, P < 0.10) plasma methylmalonic acid concentrations toward the end of
      the finishing phase. These results suggest that finishing steers require
      approximately 0.15 mg Co/kg of DM. Vitamin B12 status was not affected by Co
      source; however, the two Co sources seemed to affect certain metabolites
      differently.

PMID- 14677872
TI  - Ryegrass-based diet and barley supplementation: partition of nitrogenous
      nutrients among splanchnic tissues and hind limb in finishing lambs.
AB  - Splanchnic metabolism of nitrogenous nutrients and their uptake by the hind limb
      were studied in finishing lambs receiving ryegrass harvested at grazing stage
      with or without barley supplementation. Six multicatheterized lambs (40.2 +/- 1.5
      kg) were fed with frozen ryegrass (RG) at 690 kJ of ME intake (MEI) x d(-1) x BW(
      0.75) and 20.8 g of N intake (NI)/d successively without and with barley
      supplementation (RG + B), according to a crossover design. Barley supplementation
      represented 21% of DM intake and increased the MEI and the NI by 32 and 24%
      respectively, (P < 0.01). In the ruminal fluid, barley increased acetate and
      butyrate concentrations by 21.2 and 49.6%, respectively (P < 0.04), without any
      effect on the ammonia concentration. Consequently, the net portal appearance
      (NPA) of ammonia was not modified, but the NPA of total amino acids (TAA; +38%)
      and nonessential amino acids (NEAA; +45%) was increased (P < 0.05) by barley
      supplementation. Taken individually, the NPA of the essential amino acids (EAA)
      was increased for isoleucine (+32%; P < 0.05), threonine (+151%; P < 0.03), and
      lysine (+26%; P < 0.06), with no effect for the other EAA. In contrast to what
      was observed at the PDV level, no significant alteration in the net hepatic amino
      acid flux was observed for TAA, EAA, NEAA, branched-chain amino acids (BCAA),
      urea, and ammonia after barley supplementation, showing a relatively minor role
      of the liver in the regulation of the supply of amino acids to the peripheral
      tissues. However, taken individually, the net hepatic uptake of some NEAA
      involved in gluconeogenesis and/or ureagenesis was altered with barley
      supplementation: the alanine uptake was increased by 44% (P < 0.05), aspartate +
      asparagine (asx) uptake was decreased by 18% (P < 0.01), and glutamate +
      glutamine (glx) release tended (P < 0.10) to be increased by 208%. With barley
      supplementation, NI increased by 5 g of N/d, and net splanchnic release increased
      by 4.63 g of N/d. Consequently, the additional dietary N supply (together with
      energy supply) was nearly exclusively available to peripheral tissues as AA-N (N
      as amino acids), but no strong effect of this additional supply of AA to the hind
      limb could be demonstrated in terms of net AA hind limb fluxes. Consequently,
      barley supplementation of a ryegrass-based diet increased the net AA release by
      the splanchnic tissues, with little effect on the AA net uptake by the peripheral
      tissues.

PMID- 14677873
TI  - Effects of forage and sunflower oil levels on ruminal biohydrogenation of fatty
      acids and conjugated linoleic acid formation in beef steers fed finishing diets.
AB  - Six Hereford steers (295 kg) cannulated in the proximal duodenum were used to
      evaluate the effects of forage and sunflower oil level on ruminal
      biohydrogenation (BH) and conjugated linoleic acid (CLA) outflow. Steers were fed
      one of six treatment diets in a 3 x 2 factorial arrangement of treatments (grass
      hay level: 12, 24, or 36% of DM; and sunflower oil level: 2 or 4% of DM) in a 6 x
      6 Latin square design. The remainder of the diet was made up of steam rolled corn
      and protein/mineral supplement. Duodenal samples were collected for 4 d following
      10-d diet adaptation periods. Data were analyzed with animal, period, forage
      level, sunflower oil level, and two-way interaction between forage and sunflower
      oil level in the model. Dry matter intake showed a quadratic response (P < 0.04),
      with an increase in DMI as forage level increased from 12 to 24% followed by a
      decrease in DMI when 36% forage was fed. Flow of fatty acids at the duodenum was
      higher (P < 0.03) for 4 vs. 2% sunflower oil diets, and similar among forage
      levels. Apparent ruminal digestibility of NDF increased in a linear manner (P <
      0.04) as dietary forage level increased. Ruminal BH of dietary unsaturated 18-C
      fatty acids, oleic acid, and linoleic acid increased linearly (P < 0.05) as
      dietary forage level increased. Linoleic acid BH tended (P < 0.07) to be greater
      for 4 than 2% sunflower oil level. Duodenal flow of pentadecyclic, stearic,
      linolenic, and arachidic acids increased linearly (P < 0.05) as dietary forage
      level increased from 12 to 36%. Duodenal flow of linoleic acid decreased in a
      linear manner (P < 0.03) with increasing dietary forage level. Flow of trans-10
      octadecenoate decreased linearly (P < 0.03) as dietary forage level increased,
      whereas trans-11 vaccenic acid flow to the duodenum increased (P < 0.01) linearly
      with increased dietary forage. Dietary forage or sunflower oil levels did not
      alter the outflow of cis-9, trans-11 CLA. Flows of cis-11, trans-13, and cis-9,
      cis-11 CLA increased linearly (P < 0.05) with increased dietary forage. Flows of
      cis-11, cis-13, and trans-11, trans-13 CLA decreased linearly (P < 0.05) with
      increased dietary forage. Increasing dietary forage levels from 12 to 36% in beef
      cattle finishing diets increased BH of unsaturated 18-C fatty acid and outflow of
      trans-11 vaccenic acid to duodenum without altering cis-9, trans-11 CLA outflow.

PMID- 14677874
TI  - Corn processing method in finishing diets containing wet corn gluten feed.
AB  - Two trials were conducted to determine the effect of corn processing method on
      performance and carcass traits in steers fed finishing diets containing wet corn
      gluten feed (WCGF). In Trial 1, 480 steer calves (303 kg initial BW) were fed
      eight finishing diets: 1) dry-rolled corn (DRC) without; and 2) with 32% (DM
      basis) WCGF; 3) steam-flaked corn (SFC) without; and 4) with WCGF; 5) a
      combination of DRC and SFC without WCGF; 6) finely-ground corn (FGC) with WCGF;
      7) high-moisture corn (HMC) with WCGF; and 8) whole corn (WC) with WCGF. Feeding
      WC + WCGF increased (P < 0.10) DMI and decreased gain:feed compared with all
      other treatments. Feeding DRC + WCGF increased (P < 0.10) DMI and decreased (P <
      0.10) gain:feed compared with treatments other than WC + WCGF. Steers on
      treatments that included WCGF gained similarly, regardless of corn processing
      method, and at a rate 6% faster (P < 0.10) than steers fed diets that did not
      include WCGF. Gain:feed did not differ among steers fed SFC, SFC + WCGF, SFC +
      DRC, and HMC + WCGF. Steers fed SFC or SFC + WCGF were more efficient (P < 0.10)
      than steers fed DRC or FGC + WCGF. In Trial 2, 288 steer calves (382 kg initial
      BW) were fed six finishing diets: 1) DRC without; and 2) with 22% (DM basis)
      WCGF; 3) SFC without; and 4) with WCGF; 5) finely rolled corn (FRC) with WCGF;
      and 6) HMC corn with WCGF. Steers fed DRC + WCGF or FRC + WCGF consumed more DM
      (P < 0.10) than steers fed DRC, SFC, or SFC + WCGF. Feed intake did not differ
      between steers fed SFC + WCGF and HMC + WCGF. All treatment groups receiving WCGF
      consumed more DM (P < 0.10) feed than steers fed DRC or SFC without WCGF. Steers
      fed SFC + WCGF gained 8% faster (P < 0.10), and steers fed DRC 9.5% slower (P <
      0.10) than steers receiving all other treatments. Daily gains did not differ
      among other treatment groups. Steers fed SFC or SFC + WCGF gained 10% more (P <
      0.10) efficiently than all other treatment groups. Feed efficiency did not differ
      among steers fed DRC, DRC + WCGF, FRC + WCGF, and HMC + WCGF. Estimates for the
      NEg of WCGF calculated from animal performance indicated that WCGF contained
      approximately 25.3% more energy when fed with SFC than when fed with DRC. In
      general, more intensively processing corn improved gain:feed in finishing diets
      containing WCGF.

PMID- 14677875
TI  - Influence of grazing dormant native range or winter wheat pasture on subsequent
      finishing cattle performance, carcass characteristics, and ruminal metabolism.
AB  - A winter grazing/feedlot performance experiment repeated over 2 yr (Exp. 1) and a
      metabolism experiment (Exp. 2) were conducted to evaluate effects of grazing
      dormant native range or irrigated winter wheat pasture on subsequent intake,
      feedlot performance, carcass characteristics, total-tract digestion of nutrients,
      and ruminal digesta kinetics in beef cattle. In Exp. 1, 30 (yr 1) or 67 (yr 2)
      English crossbred steers that had previously grazed native range (n = 38) or
      winter wheat (n = 59) for approximately 180 d were allotted randomly within
      previous treatment to feedlot pens (yr 1 native range = three pens [seven
      steers/pen], winter wheat = two pens [eight steers/pen]; yr 2 native range =
      three pens [eight steers/pen], winter wheat = four pens [10 or 11 steers/pen]).
      As expected, winter wheat steers had greater (P < 0.01) ADG while grazing than
      did native range steers. In contrast, feedlot ADG and gain efficiency were
      greater (P < 0.02) for native range steers than for winter wheat steers. Hot
      carcass weight, longissimus muscle area, and marbling score were greater (P <
      0.01) for winter wheat steers than for native range steers. In contrast, 12th-rib
      fat depth (P < 0.64) and yield grade (P < 0.77) did not differ among treatments.
      In Exp. 2, eight ruminally cannulated steers that had previously grazed winter
      wheat (n = 4; initial BW = 407 +/- 12 kg) or native range (n = 4; initial BW =
      293 +/- 23 kg) were used to determine intake, digesta kinetics, and total-tract
      digestion while being adapted to a 90% concentrate diet. The adaptation and diets
      used in Exp. 2 were consistent with those used in Exp. 1 and consisted of 70, 75,
      80, and 85% concentrate diets, each fed for 5 d. As was similar for intact
      steers, restricted growth of cannulated native range steers during the winter
      grazing phase resulted in greater (P < 0.001) DMI (% of BW) and ADG (P < 0.04)
      compared with winter wheat steers. In addition, ruminal fill (P < 0.01) and total
      tract OM digestibility (P < 0.02) were greater for native range than for winter
      wheat steers across the adaptation period. Greater digestibility by native range
      steers early in the finishing period might account for some of the compensatory
      gain response. Although greater performance was achieved by native range steers
      in the feedlot, grazing winter wheat before finishing resulted in fewer days on
      feed, increased hot carcass weight, and improved carcass merit.

PMID- 14677876
TI  - Experiential learning in the animal sciences: development of a multispecies large
      animal management and production practicum.
AB  - Students enrolled in an introductory animal science course (ASG 3003) at the
      University of Florida were surveyed (n = 788) over a 3-yr period to ascertain
      their current experience and career goals in animal agriculture. Sixty-one
      percent of the students indicated that they were from an urban background. Only
      4% were raised on a farm or ranch where the majority of family income was
      attributed to production agriculture. Eighty-six percent of the students had
      minimal or no experience working with large domestic farm animals, but nearly 64%
      of the students wanted to pursue a career in veterinary medicine. Disciplinary
      and species interests of the students were highly associated with previous
      background experiences. Students from nonagricultural backgrounds, who were most
      likely to indicate a career interest involving veterinary medicine, were most
      interested (P < 0.05) in animal behavior, whereas the students of rural
      background were more interested (P < 0.05) in animal management. Thirty-three
      percent of students were primarily interested in small companion animals; 22% in
      horses; 20% in domestic farm animals, including beef, dairy, swine, or sheep; and
      24% in undomesticated zoo animals or wildlife. The career goals indicated by most
      students necessitate practical application of animal husbandry skills that are
      often assumed as general knowledge. Thus, a multispecies large animal management
      and production practicum (ANS 3206) was developed to provide students with hands
      on experience. It was an elective course, and students were encouraged to enroll
      for two consecutive semesters. Teams of students rotated responsibilities among
      four livestock species (beef, dairy, equine, and swine). Daily responsibilities
      at each of the units included feeding and monitoring growth of feedlot cattle and
      finishing swine, farrowing assistance and baby pig processing, and equine
      training and foaling assistance. Students were also involved with all facets of a
      working dairy. Additionally, students completed written assignments specific to
      their individual species responsibilities that included daily journals,
      worksheets, or calculation of performance measures. Weekly class meetings allowed
      for instruction and were used to manage the varied course activities. Using a 5
      point scale (1 = poor, 5 = excellent), students indicated that the course further
      stimulated their interest (4.73) and facilitated their learning (4.63) of animal
      science concepts. Overall course evaluations ranged from 4.54 +/- 0.55 to 4.85 +/
      0.38 over a 4-yr period. As more students enter animal science programs with
      nonagricultural backgrounds, it will become necessary to reemphasize basic animal
      handling skills and practical applications through experiential learning
      activities.

PMID- 14677877
TI  - Diet and evaluators affect perception of swine waste odor: an educational
      demonstration.
AB  - An educational program was developed for extension agents, faculty, and graduate
      students to illustrate the effect of diet composition on odor from swine manure.
      Participants in this program first received a 2-h detailed review on odorous
      compounds in manure and the effect of diet on odor. For the second portion of the
      training, nine manure samples were used from pigs fed diets formulated with feed
      ingredients predicted to have different effects on odor emission or a
      nutritionally adequate corn-soybean meal diet. Participants were instructed to
      rate the odor from these samples for pleasantness, irritation, and intensity on a
      scale of 0 (best) to 8 (worst), using manure from the corn-soybean meal fed pig
      as the reference with a score defined as 4 for each variable. Results obtained
      were summarized and discussed before concluding the program. Participants were
      Cooperative Extension Agents (n = 13) with swine responsibilities and graduate
      students and faculty (n = 8). The manure from the diet with the worst odor scores
      (1% garlic) was rated at 70% more odorous across the three odor variables (P <
      0.05) than the diet with the least odorous manure (purified diet). Even though a
      reference sample was used, individual participants differed in their perception
      of irritation across samples (P < 0.05), ranging in average score across diets
      from 2.4 (moderately better than reference) to 5.0 (slightly worse than
      reference). With extension agents, a 1 to 7 scale (very interesting to not at all
      interesting) was used for evaluation of the training session. Participants found
      the material to be interesting (mean = 1.7, SD = 0.7) and the training exercise
      to be well organized and coherent in its presentation (mean = 1.8, SD = 0.7).
      Participants enjoyed this training and learned that differences in odor are
      achievable through altering diet composition, and that the response to swine odor
      depends on individual odor perception.

PMID- 14677878
TI  - Symposium on analytical method challenges for measuring nutrients and
      antinutrients in plants: introduction to the symposium.

PMID- 14677879
TI  - A survey of methods of analysis for minerals in feedstuffs.
AB  - A wide range of minerals occurs in feedstuffs as naturally occurring and
      purposely added elements, as well as by adventitious contamination. These mineral
      elements can generally be classified as nutritionally essential major elements,
      nutritionally essential minor and trace elements, and those regarded as toxic or
      with an essential/toxic duality. A survey is presented of methods used for the
      determination of major, minor, and trace elements in feedstuffs and related
      biological materials. Currently available methods include the following: atomic
      absorption spectrometry, atomic emission spectrometry, mass spectrometry, neutron
      activation analysis, x-ray emission spectrometry, molecular light absorption
      spectrometry, molecular fluorometry, electrochemistry, Kjeldahl method
      (nitrogen), combustion elemental analysis, volumetry, ion chromatography, and
      gravimetry. Available reference, routine, official, unofficial, and recommended
      methods are reviewed as a basis for recommendations of methods most suitable for
      feedstuffs.

PMID- 14677880
TI  - Challenges with nonfiber carbohydrate methods.
AB  - Nonfiber carbohydrates (NFC) encompass a compositionally and nutritionally
      diverse group exclusive of those carbohydrates found in NDF. Their content in
      feeds has often been described as a single value estimated by difference as 100%
      of dry matter minus the percentages of CP, NDF (adjusted for CP in NDF), ether
      extract, and ash. A calculated value was used because of difficulties with assays
      for individual NFC, but it does not differentiate among nutritionally distinct
      NFC. Errors in NFC estimation can arise from not accounting for CP in NDF and
      when multipliers other than 6.25 are appropriate to estimate CP. Analyses that
      begin to distinguish among NFC are those for starch, soluble fiber (non-NDF,
      nonstarch polysaccharides), and low molecular weight carbohydrates (mono- and
      oligosaccharides). Many starch analyses quantify alpha-glucans through specific
      hydrolysis of alpha-(1 --> 4) and alpha-(1 --> 6) linkages in the glucan, and
      measurement of released glucose. Incomplete gelatinization and hydrolysis will
      lead to underestimation of starch content. Starch values are inflated by enzyme
      preparations that hydrolyze carbohydrates other than alpha-glucan, measurement of
      all released monosaccharides without specificity for glucose, and failure to
      exclude free glucose present in the unhydrolyzed sample. Soluble fiber analyses
      err in a fashion similar to NFC if estimation of CP requires multipliers other
      than 6.25, or if contaminants such as CP and starch have not been properly
      accounted. Depolymerization and incomplete precipitation can also decrease
      soluble fiber estimates. The low molecular weight carbohydrates have been defined
      as carbohydrates soluble in 78 to 80% ethanol, which separates them from
      polysaccharides. They can be measured in extracts using broad-spectrum
      colorimetric assays (phenol-sulfuric acid assay or reducing sugar analysis of
      acid hydrolyzed samples) or chromatographic methods. Limitations of the
      colorimetric assays include lack of differentiation among mono- and
      oligosaccharides and differences in efficacy of measuring total carbohydrate.
      More sensitive and precise chromatographic methods require expensive equipment
      and specialized expertise. Current methods for NFC can separate nutritionally
      relevant fractions, but questions remain as to which fractions merit analysis and
      what analyses to use. These issues must be resolved in order to soundly evaluate
      and explore the roles of carbohydrates in diets.

PMID- 14677881
TI  - Challenges in measuring insoluble dietary fiber.
AB  - Objectives of this review are to define criteria for evaluating insoluble dietary
      fiber (IDF) methods, discuss their relevance in meeting the nutritional needs of
      ruminants and herbivores, describe problems with empirical IDF methods, and
      assess their relative merits. The challenge for the researcher, nutritionist, and
      analyst is to select fiber methods that are relevant and reproducible. Without
      relevance, there is no reason to measure IDF, and without reproducibility, there
      is no value in doing so. Insoluble dietary fiber is a complex matrix of chemical
      components, and there are no primary standards that can be used to establish the
      validity of methods. Thus, the definition of fiber is crucial in determining
      method relevance. For ruminants and nonruminant herbivores, the appropriate
      physiological definition for selecting IDF methods may be as follows: the organic
      fraction of the diet that is indigestible or slowly digesting and occupies space
      in the gastrointestinal tract. Crude fiber does not match this definition, and
      its use should be abandoned. Acid detergent fiber does not measure all IDF but is
      useful when included with other dietary fiber methods to describe some feeds.
      Several current methods, including amylase-treated neutral detergent fiber (aNDF)
      and enzymatic-gravimetric methods, are relevant for measuring IDF. In a
      collaborative study, aNDF obtained a standard deviation of reproducibility
      (SD(R)) of 1.3%. Enzymatic-gravimetric methods of measuring IDF have been
      evaluated using too few feed materials to make statistically valid conclusions,
      but the SD(R)f IDF, for the few feeds evaluated, were similar to aNDF (0.9 to
      2.4%). The enzymatic-chemical method of measuring IDF as the sum of insoluble
      nonstarch polysaccharides and lignin agrees with NDF, but the SDR of neutral
      sugar analysis using acid hydrolysis and chromatography is greater (3.2%) than
      other dietary fiber methods. Empirical methods--such as those used to measure
      IDF, although based on nutritional concepts--actually define the fraction being
      measured and must be followed exactly, without modification. The selection of a
      suitable method for IDF depends on the purpose of analysis. Analysis of sugars in
      insoluble polysaccharides provides more information but is less reproducible and
      more expensive to obtain. For routine nutritive evaluation of feeds and
      formulation of rations, aNDF seems to be a reasonable choice for measuring IDF
      based on relevance and reproducibility.

PMID- 14677882
TI  - Challenges with fats and fatty acid methods.
AB  - The content and chemical nature of lipids in feedstuffs is heterogeneous. It has
      long been known that ether extraction by the Weende procedure inadequately
      characterizes the fat content of feedstuffs, yet it remains the official method.
      Diethyl ether (or hexanes that are often used) extracts significant amounts of
      nonnutritive, nonsaponifiable lipids from forages, and often incompletely
      extracts lipids of nutritional value, especially fatty acids present as salts of
      divalent cations. Preextraction hydrolysis of insoluble fatty acid salts with
      acid releases these fatty acids, and this step is included in the official
      procedure for certain feedstuffs in the United Kingdom; however, acid hydrolysis
      increases analysis time and decreases precision. Acid hydrolysis also causes
      confusion as to the proper definition of the fat content of feedstuffs. A
      preferred method of fat analysis determines the total fatty acid concentration in
      feed samples by converting fatty acid salts, as well as the acyl components in
      all lipid classes, such as triacylglycerols, phospholipids, and sphingolipids, to
      methyl esters using a simple, direct one-step esterification procedure. Fatty
      acid methyl esters are then quantified by GLC, which provides information on both
      fatty acid quantity and profile in a single analysis. Adjustments in conditions
      and reagents may be necessary to overcome difficulty in quantitatively preparing
      esters from certain types of fatty acids and their derivatives in commercial fat
      supplements. After correction for glycerol content, analysis of oils by this
      procedure provides information on the content of nonsaponifiable material, such
      as chlorophyll, waxes, and indigestible polymers formed from heat- or oxidatively
      damaged fats. The correct description of feedstuffs for energy value of fats is
      the content of total fatty acids.

PMID- 14677883
TI  - Challenges in measuring moisture content of feeds.
AB  - Accurate determination of the moisture (water) content in individual feed
      ingredients and mixed feeds is critical throughout the feed industry. Most
      analytical methods used to determine apparent water content of feedstuffs are
      empirical, estimating water by evaporation and loss of weight on drying (oven
      drying methods). These methods differ greatly in effectiveness, resulting in
      bias. Bias associated with measuring the water content of feedstuffs is a concern
      not only because of the lack of confidence in the moisture value itself, but also
      because moisture determinations affect accurate quantification and expression of
      other nutrient values. Methods for determining moisture in feeds have frequently
      been borrowed from the cereal, forage, or other applications without validating
      the extension of the method. Methods such as Karl Fischer titration measure water
      by direct comparison to a calibration standard for water and can be used as
      reference methods for the evaluation of empirical methods. The objective of this
      paper is to review methods for determining moisture, review comparisons among
      moisture methods for various feedstuffs, make recommendations for a reference
      method, and make general recommendations toward improving the results of moisture
      testing. The need to evaluate and improve moisture methods and standardize
      practices in laboratories is evident from this study. It also is evident that the
      methods appropriate for a specific feed ingredient or feed should not be extended
      to all feeds without proper validation to the new matrices. Part of the
      validation for empirical methods should be comparison to Karl Fischer or other
      the direct methods. It also is recommended that the results obtained using oven
      methods not be termed "moisture;" rather, they should be termed "loss on drying,"
      and the drying conditions should become part of the term.

PMID- 14677884
TI  - Public-private mix for DOTS: demanding, but delay will only hamper TB control.

PMID- 14677885
TI  - Clemens Freiherr von Pirquet and the tuberculin test.

PMID- 14677886
TI  - Severe acute respiratory syndrome.
AB  - Severe acute respiratory syndrome (SARS) is a new disease that poses a threat to
      international health. The SARS epidemic earlier this year affected more than 30
      countries and regions, with a cumulative global total of 8098 cases. It is caused
      by a novel coronavirus, probably of animal origin. The mean incubation period is
      6.4 days (range 2-11 days). Patients usually present with high fever, chills,
      myalgia and dry cough, with or without chest X-ray evidence of pneumonia at the
      onset of disease. A history of contact with or travel to an area with local
      transmission is common. Diagnosis is based on clinical criteria, as a valid rapid
      diagnostic test is not yet available. There is no specific antiviral therapy for
      this disease, and no controlled clinical trial for any treatment modality has
      been conducted. In several retrospective studies steroids have been shown to be
      useful in a proportion of patients who deteriorated despite antibiotics and
      supportive treatment. SARS has a high morbidity (about 25% required intensive
      care) and fatality (9.6%). A high index of suspicion for the disease, isolation
      of patients, strict observation of infection control practices and compliance
      with use of personal protective equipment are necessary to prevent nosocomial
      infection. Contact tracing and quarantine are essential measures to prevent
      community spread of disease. Prevention of future outbreaks requires
      strengthening of infection control practices in hospitals, development of a rapid
      diagnostic test and a vaccine, and removal of any animal reservoir and
      environmental conditions that led to the spread of the disease.

PMID- 14677887
TI  - Feasibility and effectiveness of a public-private mix project for improved TB
      control in Delhi, India.
AB  - SETTING: New Delhi, India. OBJECTIVE: To assess the feasibility of a public
      private mix (PPM) project for improved tuberculosis (TB) control and determine
      its impact on case detection, case-management quality, treatment outcome and
      patient convenience. DESIGN: 1) Monitoring of case detection through the review
      of record data; 2) cohort analysis of patients treated by private providers
      (PPs); 3) questionnaire-based surveys of patients and private providers. RESULTS:
      A total of 612 cases were detected, of whom 168 (27%) were new sputum-positive
      cases. Incremental case notification due to PPs was 47% for new cases and 29% for
      new sputum-positive cases. Sputum examination for diagnosis and evaluation was
      performed in 100% and 84%, respectively, of notified patients. The treatment
      success rate for new sputum-positive cases treated by PPs was 81%, which was not
      significantly different from the 86% in the public sector. Directly observed
      treatment (DOT) was confirmed by 95% of patients. CONCLUSIONS: This PPM project,
      carried out with government funding in accordance with the RNTCP recommendations
      and with the support from several government and private organisations, achieved
      improved case detection as well as acceptable treatment outcome for patients
      receiving DOT from PPs.

PMID- 14677888
TI  - Treatment results among tuberculosis patients treated by private lung specialists
      involved in a public-private mix project in Vietnam.
AB  - SETTING: Ho Chi Minh City, Vietnam. OBJECTIVES: To determine treatment outcome
      among patients treated by private lung specialists in a public-private mix (PPM)
      project for improved TB control. METHODS: Cohorts of patients treated by private
      lung specialists within the PPM project and in National Tuberculosis Programme
      (NTP) facilities were followed for up to 12 months. The quality of case
      management and treatment outcome was determined based on information in treatment
      cards. As a complement, questionnaire surveys of private providers (PPs) and
      patients and focus group discussions with PPs were conducted. RESULTS: Among 400
      patients treated by PPs, 36 different treatment regimens were used. Directly
      observed treatment was not used at all, and treatment evaluation with sputum
      smear microscopy and health education was inadequate. Overall treatment success
      was 60% and the default rate was 37%, which was considerably worse than in NTP
      facilities. CONCLUSION: This PPM project, which used a combination of training,
      supervision, standardised referral and information system and financial
      incentives, did not achieve sufficiently good treatment outcome by PPs. Possible
      reasons for the poor outcome include absence of subsidisation of drug costs and
      lack of regulatory enforcement.

PMID- 14677889
TI  - Referring TB suspects from private pharmacies to the National Tuberculosis
      Programme: experiences from two districts in Ho Chi Minh City, Vietnam.
AB  - SETTING: Ho Chi Minh City, Vietnam. OBJECTIVE: To describe pharmacists' attitudes
      towards referring TB suspects to the National Tuberculosis Programme (NTP) and to
      evaluate the feasibility of a new referral system. METHODS: 1) Questionnaire
      survey of 150 private pharmacies; 2) qualitative interviews with 16 pharmacists;
      3) monitoring the use of new referral forms for 21 months. RESULTS: Use of a
      simple referral form was thought to be manageable by 72% of the pharmacists.
      Pharmacists identified a number of different types of risks associated with
      referral of TB suspects to the NTP; clients could turn to another pharmacy (61%
      of respondents); criticise the pharmacist if it appears that they do not have TB
      (42%); or remain untreated because they are not able to visit the NTP (41%).
      Fifty-eight (39%) of eligible pharmacies referred at least one client. At least
      373 suspects were referred, 149 were tested and 10 had TB. CONCLUSIONS: It is
      feasible to let pharmacies refer TB suspects. For there to be a significant
      impact on case detection, it is important to acknowledge a number of concerns
      expressed by pharmacists and attempt to change both clients' and providers'
      expectations with regard to the pharmacists' role.

PMID- 14677890
TI  - A baseline survey of the prevalence of tuberculosis in a community in south India
      at the commencement of a DOTS programme.
AB  - OBJECTIVE: To determine the baseline prevalence of culture-positive and smear
      positive tuberculosis and the annual risk of tuberculous infection (ARTI) in a
      community in south India where DOTS is being implemented. METHODS: Using cluster
      sampling, 50 rural panchayats (villages) and three urban units in Tiruvallur
      district were selected randomly. All adults aged > or = 15 years underwent
      symptom and radiographic examination, and those with abnormal shadows and/or
      chest symptoms had sputum smear and culture examination. In another cluster
      sample of 73 villages and three urban units, all children aged < 10 years were
      tuberculin tested. RESULTS: The prevalence of culture-positive and smear-positive
      tuberculosis was respectively 605 and 323/100,000. Both increased appreciably
      with age, and were substantially higher in males than in females at all ages; the
      overall male:female ratio was 5.5 for culture-positive and 6.5 for smear-positive
      tuberculosis. The ARTI in children aged under 10 years was 1.6%, and was
      unaffected by sex. Over three decades there was an overall decline of 1.8% per
      annum in the prevalence of culture-positive and 2.1% for smear-positive
      tuberculosis. CONCLUSION: Tuberculosis is a major problem in this rural community
      in south India, with a prevalence of 605/100,000 for culture-positive
      tuberculosis and 323/100,000 for smear-positive tuberculosis.

PMID- 14677891
TI  - A comprehensive comparison of Ziehl-Neelsen and fluorescence microscopy for the
      diagnosis of tuberculosis in a resource-poor urban setting.
AB  - SETTING: Nairobi City Council Chest Clinic, Kenya. OBJECTIVES: To establish the
      efficiency, costs and cost-effectiveness of six diagnostic strategies using Ziehl
      Neelsen (ZN) and fluorescence microscopy (FM). DESIGN: A cross-sectional study of
      1398 TB suspects attending a specialised chest clinic in Nairobi subjected to
      three sputum examinations by ZN and FM. Lowenstein-Jensen culture was used as the
      gold standard. Cost analysis included health service and patient costs. RESULTS:
      Of 1398 suspects enrolled, 993 (71%) had a complete diagnostic work-up involving
      three sputum specimens for ZN and FM, culture and chest X-ray (CXR). Irrespective
      of whether ZN or FM was used on one, two or three smears, the overall diagnostic
      process detected 92% culture-positive cases. Different strategies affected the
      ratio of smear-positive to smear-negative TB; however, FM was more sensitive than
      ZN (P < 0.001). FM performance was not affected by the patient's HIV status. The
      cost per correctly diagnosed smear-positive case, including savings, was 40.30 US
      dollars for FM on two specimens compared to 57.70 US dollars for ZN on three
      specimens. CONCLUSION: The FM method used on one or two specimens is more cost
      effective and shortens the diagnostic process. Consequently, more patients can be
      put on a regimen for smear-positive TB, contributing to improved treatment and
      reducing transmission.

PMID- 14677892
TI  - Simultaneous measurement of T-helper 1 cytokines in tuberculous pleural effusion.
AB  - OBJECTIVE: Tuberculosis, the leading cause of death among infectious diseases
      worldwide, is a major cause of lymphocytic exudative pleural effusion. T-helper 1
      cytokines, including interferon-gamma (IFN-gamma), interleukin (IL)-12p40 and IL
      18 are predominantly associated with cell-mediated immune responses, and play an
      important role in immunity to Mycobacterium tuberculosis. DESIGN: We studied 55
      patients presenting with pleural effusion at the National Sanyo Hospital between
      April 2000 and September 2001 (42 men and 13 women; mean age 67 years). Twenty
      patients (36%) had tuberculous pleurisy, while 18 (33%) had malignant effusions
      and 17 (31%) had an effusion with another aetiology. Pleural fluid concentrations
      of IL-12p40 and IL-18 as well as IFN-gamma measured by enzyme-immunoassays.
      RESULTS: Concentrations of all three cytokines were significantly higher in
      tuberculous than other pleural effusions. Significant correlations were evident
      between IFN-gamma and IL-12. We found particularly high concentrations of IL
      12p40 and IFN-gamma in tuberculous patients with high fever. CONCLUSION: The
      results indicate that T-helper 1 cytokines are involved in intrapulmonary
      cellular immune responses to M. tuberculosis, and suggest that the interactions
      between them may play an important role in the pathogenesis and severity of the
      pleural effusion. Understanding the development of this response may enhance our
      understanding of the pathogenesis of tuberculous pleural effusion and suggest new
      therapies.

PMID- 14677893
TI  - Extra-pulmonary manifestations in a large metropolitan area with a low incidence
      of tuberculosis.
AB  - BACKGROUND: The increases in extra-pulmonary tuberculosis (EPTB) have been
      largely due to human immunodeficiency virus co-infection. The rates of EPTB have
      remained constant despite the decline in pulmonary tuberculosis (PTB) cases.
      OBJECTIVE: To evaluate covariates associated with EPTB. METHODS: A 4-year cohort
      of EPTB patients was compared with PTB cases. Enrollees were assessed for TB
      risk, medical records were reviewed, and Mycobacterium tuberculosis isolates were
      fingerprinted. RESULTS: We identified 538 EPTB cases (28.6%) in a total of 1878
      enrollees. The most common sites of infection were lymph nodes (43%) and pleura
      (23%). EPTB cases included 320 (59%) males, 382 (71%) patients were culture
      positive, and 332 (86.9%) patient isolates were fingerprinted. Fewer EPTB than
      PTB patients belonged to clustered M. tuberculosis strains (58% vs. 65%; P =
      0.02). A multivariate model identified an increased risk for EPTB among African
      Americans (OR = 1.9, P = 0.01), HIV-seropositive (OR = 3.1, P < 0.01), liver
      cirrhosis (OR = 2.3, P = 0.02), and age <18 years (OR = 2.0, P = 0.04). Patients
      with concomitant pulmonary and extra-pulmonary infections were more likely to die
      within 6 months of TB diagnosis (OR = 2.3, P < 0.01). CONCLUSIONS: African
      American ethnicity is an independent risk factor for EPTB. Mortality at 6 months
      is partly due to the dissemination of M. tuberculosis and the severity of the
      underlying co-morbidity.

PMID- 14677894
TI  - Tuberculous radiculomyelitis: review and presentation of five patients.
AB  - BACKGROUND: The southeast region of Iran is an endemic area for tuberculosis.
      Tuberculous radiculomyelitis (TBRM) was considered a rare form of parenchymal
      neurotuberculosis. OBJECTIVE: To analyze the clinical, laboratory and
      electrophysiological data of patients with TBRM. We report five patients and
      review the literature. METHOD: We searched Medline since 1966 and reviewed all
      cases of TBRM, excluding those with Pott's disease. We then evaluated the
      clinical and electrophysiological data of our patients. RESULTS: Five patients
      (two men), with a mean age of 25 years, were assessed. The mean duration of
      symptoms before diagnosis was 4.5 weeks. Three patients had clinical
      manifestation of tuberculous meningitis (TBM). Diagnosis was based on sputum
      smear and culture, cerebrospinal fluid (CSF) culture and polymerase chain
      reaction (PCR) gene amplification of Mycobacterium tuberculosis. Paraparesis or
      paraplegia, sphincter incontinence and Babinski sign were the main clinical
      features. CSF analysis was compatible with chronic meningitis. Electromyography
      showed radiculopathy in all patients and peripheral nerve disease secondary to
      axonal damage in only three, while myelography showed adhesive arachnoiditis in
      three. CONCLUSION: Despite the rarity of TBRM, clinical features were well
      described. To prevent neurological sequelae, early diagnosis and treatment is
      mandatory. Electrophysiological study may predict the prognosis.

PMID- 14677895
TI  - Analysis of multidrug-resistant Mycobacterium bovis from three clinical samples
      from Scotland.
AB  - OBJECTIVE: To determine whether multidrug-resistant (MDR) strains of
      Mycobacterium bovis isolated from patients in Scotland were genotypically
      related. DESIGN: Genotypes of MDR strains were determined using three molecular
      fingerprinting techniques: pulsed-field gel electrophoresis (PFGE), spoligotyping
      and restriction fragment length polymorphism (RFLP). PFGE profiles were also
      obtained for all medical and veterinary isolates occurring in Scotland in 1997
      1998. RESULTS: MDR strains showed individual Dra I PFGE profiles. Case III/98 had
      a profile represented in both veterinary and medical populations, Case I/94 had a
      profile observed in medical but not veterinary isolates, and Case II/98 had a
      profile unique to this study. Afl II PFGE discriminated the resistant strains.
      Spoligotyping grouped Cases I/94 and II/98 (ST-134). Case III/98 had a
      spoligotype ST-140, which is commonly observed in veterinary isolates. Similarly,
      DRr-RFLP analysis grouped cases I/94 and II/98, whereas Case III/98 had a common
      veterinary profile. DRX(PGRS) RFLP gave three unique profiles. CONCLUSION: Three
      resistant strains were discriminated by PFGE and DRX(PGRS) RFLP, indicating that
      the three strains are not related in an epidemiologically relevant time scale.
      However, Cases I/94 and II/98 were more closely linked by spoligotyping and DRr
      RFLP data. PFGE and DRr-RFLP linked Case III/98 profiles to the most common
      veterinary isolate.

PMID- 14677896
TI  - The relationship between mediastinal lymph node attenuation with parenchymal lung
      parameters in silicosis.
AB  - OBJECTIVE: Attenuation changes on computed tomography (CT) in mediastinal lymph
      nodes (LN) may be related to lung alterations and functional impairment in
      silicosis. DESIGN: CT and clinical data of 41 (64.2 +/- 8.3 years) males with
      silicosis were retrieved. Attenuation type (calcified, hyperdense, normodense)
      and calcification pattern (central, eccentric, dense, eggshell, speckled) of
      mediastinal LN were evaluated; LN attenuation of uncalcified LNs quantified on CT
      in six LN stations. Nodular profusion (CT-NP) and progressive massive fibrosis
      (CT-PMF) were graded. Relationships between LN, CT, lung function and clinical
      parameters were determined. RESULTS: LN sites were paratracheal (n = 39),
      subcarinal (n = 39), tracheobronchial (n = 37), aortopulmonary (n = 37), hilar (n
      = 27), and peri-oesophageal (n = 21). LNs were calcified, hyperdense and
      normodense in 107, 85 and 54 LN stations, respectively. Uniformly calcified LN
      was most common, followed by speckled calcification. Central, eccentric and
      eggshell calcification was rare. CT-NP scores > or = 16 were associated with
      higher LN attenuation and number of calcified LN stations than CT-NP scores < 16.
      PMF had no influence over LN morphology or calcification pattern. LN attenuation
      correlated with CT-PMF (r = 0.36, P = 0.01), CT-NP (r = 0.54, P < 0.001) and
      DLCO/VA (r = -0.33, P = 0.02). CONCLUSION: Uniformly calcified and hyperdense LNs
      are common in silicosis, and eggshell LN calcification is rare. There are
      associations between LN attenuation and lung function impairment, and CT grades
      of nodular profusion and PMF.

PMID- 14677897
TI  - Dual infection with Streptococcus pneumoniae and Mycobacterium tuberculosis in
      HIV-seropositive patients with community acquired pneumonia.
AB  - Pulmonary infections with more than one organism are common in human
      immunodeficiency virus (HIV) seropositive patients. We describe nine cases of
      dual infection with Streptococcus pneumoniae and Mycobacterium tuberculosis in
      HIV-seropositive patients presenting with community acquired pneumonia (CAP). It
      is important to exclude pulmonary tuberculosis in HIV-seropositive patients with
      CAP who fail to respond appropriately to initial antibiotic therapy, even if
      another etiological pathogen has been found.

PMID- 14677898
TI  - Hemoptysis secondary to fistulisation of Pott's abscess.

PMID- 14677899
TI  - Familial clustering of rifampin-induced acute renal failure.

PMID- 14677900
TI  - Drug packaging: what can TB learn from leprosy control?

PMID- 14677901
TI  - Drug packaging: would 'blister packs' improve compliance and is 'one-box, one
      patient' of interest for TB control programmes?

PMID- 14677902
TI  - Aeroallergens in clinical practice of allergy in India. An overview.
AB  - Allergic diseases such as bronchial asthma, allergic rhinitis and atopic
      dermatitis are dramatically increasing all over the world including developing
      countries like India. Today, more than 30 % of the population is known to suffer
      from one or other allergic ailment. Major causative agents implicated are pollen
      grains, fungal spores, dust mites, insect debris, animal epithelia, etc. Several
      aerobiological studies have been conducted in different parts of the country to
      ascertain aerial concentration and seasonality of pollen grains and fungi.
      Recently, an "All India Coordinated Project on Aeroallergens and Human Health"
      was undertaken to discover the quantitative and qualitative prevalence of
      aerosols at 18 different centres in the country. Predominant airborne pollen are
      Holoptelea, Poaceae, Asteraceae, Eucalyptus, Casuarina, Putanjiva, Cassia,
      Quercus, Cocos, Pinus, Cedrus, Ailanthus, Cheno/Amaranth, Cyperus, Argemone,
      Xanthium, Parthenium and others. Clinical and immunological evaluations have
      revealed allergenically important texa - some of them for the first time.
      Allergenically important pollen are Prosopis juliflora, Ricinus communis, Morus,
      Mallotus, Alnus, Querecus, Cedrus, Argemone, Amaranthus, Chenopodium, Holoptelea,
      Brassica, Cocos, Cannabis, Parthenium, Cassia and grasses. Further cross
      reactivity of the IgE antibodies is a common phenomenon among various pollen
      allergens. Ricinus communis pollen from commonly growing weeds in India, cross
      reacts with latex (Hevea brasiliensis), Mercurialis annua and also with seeds of
      Ricinus communis - all belonging to family Euphorbiaceae. Areca catechu cross
      reacts with other members of Arecaceae such as Phoenix sylvestris, Cocos nucifera
      and Borassus flabelifer. Several reports on pollen and fruit syndrome have been
      analyzed. Experiments conducted by us revealed that pollutants (NO(2) and SO(2))
      not only affect pollen morphology but also changes their allergenic potency.
      Immunotherapy with recombinant proteins having similar epitopes from different
      allergens have been advocated, besides allergen avoidance.

PMID- 14677903
TI  - Canine ehrlichiosis.
AB  - Ehrlichia spp. are obligate intracellular bacteria with tropism for hematopoietic
      cells. Monocytic ehrlichioses in dogs and humans are transmitted by ticks and
      primarily caused by E. canis and E. chaffeensis, respectively. E. canis causes
      canine monocytic ehrlichioses (CME), a potentially fatal disease in dogs that
      requires rapid and accurate diagnosis in order to initiate appropriate therapy
      leading to a favorable prognosis. CME is characterized by three stages; 1) acute,
      2) subclinical and 3) chronic. Dogs infected with E. canis remain infected for
      their entire lives, even after receiving antibiotic treatment with doxycycline.
      The prevalence of E. canis is dependent on the distribution of the vector,
      Rhipicephalus sanguineus tick, which occurs mainly in tropical and subtropical
      regions. The agent causing canine granulocytic ehrlichiosis (CGE) in Europe has
      been determined by nucleotide sequencing of the 16S rRNA gene to be similar to
      both Ehrlichia equi and E. phagocytophila (Anaplasma phagocytophila), and is
      identical to the agent of human granulocytic ehrlichiosis (HGE). The vector of
      this pathogen in Europe is the common European tick, Ixodes ricinus and its
      reservoir - wild and domestic animals. Two distinct clinical disease syndromes,
      including chronic, moderate to sever anemia and polyarthritis, are associated
      with CGE. In areas infested with vectors of tick-borne agents known to be endemic
      for Lyme disease, veterinarians may suspect ehrlichiosis in dogs.

PMID- 14677904
TI  - Characterisation of pollen allergens.
AB  - Allergy is hypersensitive reaction by the body to foreign substances (antigens)
      which in similar amounts and circumstances are harmless within the bodies of
      other people. The allergic response develops when the natural immune defence
      mechanism, responsible for the correct reaction to environmental agents, is
      disturbed. The allergens are divided into those originating from the natural
      environment and those from a chemically contaminated environment. The most
      frequent allergens from the natural environment are inhalant ones present in
      pollen grains, mould fungi spores and in fragments of mycelial hyphae. The
      airborne allergens also include: bacteria, house dust mites, epidermis of house
      pets, allergens of some food products and insect venom. The allergens originating
      from the natural environment are usually proteins, being high-molecular compounds
      of molecular weight higher than 10 kDa. Pollen allergens are water-soluble
      proteins or glycoproteins of molecular masses from 10-70 kDa. Many of them are
      resistant to pH changes and high temperature, even up to 100 degrees C. Apart
      from pollen grains, allergens can occur in other parts of plants: roots, stems,
      leaves, seeds or fruit, in substances excreted by plants, such as juice and
      volatile oils, or in other bioaerosols of plant origin, e.g. fluids released
      during treatment of some crops. Proteins of some antigens show some analogies in
      the amino acids sequence, which determine immunological similarity and cross
      reactivity. From among factors conducing pollen allergy the most important are
      genetic and environmental ones (air pollution, exposure to allergens, infections
      of respiratory tract, diet) and microflora of pollen grains.

PMID- 14677905
TI  - Biofilm and dental unit waterlines.
AB  - Aquatic biofilms, which are well-organized communities of microorganisms, are
      widespread in nature. They constitute a major problem in many environmental,
      industrial and medical settings. The use of advanced techniques has revealed
      biofilm structure, formation and ecology. Special attention was given to the
      build-up of biofilm in dental unit waterlines (DUWLs), which are small-bore
      flexible plastic tubing to bring water to different handpieces. They are coated
      with well-established biofilms. Active biofilm is a source of microbial
      contamination of DUWLs water. The safety of dental treatment requires a good
      quality of the water used. The knowledge of nature, formation and the ways to
      eliminate the biofilm is the first step towards reducing health risk, both for
      patients and dental personnel. The article reviews these issues.

PMID- 14677906
TI  - Occupational exposure to airborne fungi among rice mill workers with special
      reference to aflatoxin producing A. flavus strains.
AB  - A study was undertaken on environmental mycoflora of rice mills situated in Bawla
      town, Ahmedabad district. The airborne fungal communities were isolated and
      identified quantitatively by using Andersen-6-stage viable sampler, midget
      impinger and high volume samplers (Cone and Hexhlet for total and respirable
      dusts respectively). Of all the isolates, genus Aspergillus was predominant and
      among the Aspergillus species, A. flavus was the common isolate, irrespective of
      the method applied for sample collection. Number of isolates recovered from the
      working place was significantly greater (p < 0.01) compared to control. Total
      percentage of aflatoxin positive strains of A. flavus was 8 %. These aflatoxin
      producing strains were identified on various media, such as Czapek agar (Cz) with
      0.05 % anisaldehyde, APA and CAM. Surface morphology of aflatoxin positive
      strains was studied by SEM. Highly significant total and respirable dust
      concentrations were found in the work place (p < 0.01) whereas in the store, only
      the total dust concentration was significantly higher (p < 0.05) than the control
      site. The study indicates that the rice mill workers are occupationally exposed
      to airborne aflatoxin producing strains of A. flavus. Thus, they require
      protective mask for their safety.

PMID- 14677907
TI  - Biological characterisation of Cryptosporidium parvum isolates of wildlife
      rodents in Poland.
AB  - The study was undertaken to characterise the C. parvum isolates originating from
      naturally infected woodland and field rodents: Clethrionomys glareolus (CG),
      Apodemus flavicollis (AF) and Microtus arvalis (MA). We found that the
      measurements of oocyst dimensions and oocyst morphology did not allow distinction
      between the parasite isolates from the 3 rodent species. The mean dimensions
      were: for CG 4.67 x 4.21, for AF 4.65 x 4.14 and for MA 4.66 x 4.16. These 3
      groups of isolates have produced significantly different pictures of infection in
      C57BL/6 mice. The overall mean oocysts output was: in CG-mice 41,739, in AF-mice
      18,000, in MA-mice 10,384 oocysts/1 g of faeces. From these data we suggest that
      rodent isolates of C. parvum could represent new subgroups in so-called "mouse"
      C. parvum strain. The successful cross-transmission from wild hosts to laboratory
      rodents and the close similarity of COWP sequence between our isolates and
      "mouse" genotype and between "mouse" and zoonotic genotype of C. parvum (genotype
      C) inform us that all these isolates should be treated as potentially hazardous
      for human health.

PMID- 14677908
TI  - Detection of Borrelia burgdorferi sensu lato DNA in Ixodes ricinus ticks in North
      western Poland.
AB  - In order to estimate the risk of contracting Lyme disease in the forest areas of
      north-western Poland, PCR-based studies were carried out on 6,817 Ixodes ricinus
      ticks for infection by the spirochaete B. burgdorferi sensu lato (s.l.). The
      studies were performed using the primers for the fla gene, conserved for all
      European genospecies of B. burgdorferi s.l. Based on the incidence of B.
      burgdorferi s.l. DNA in I. ricinus ticks at eight sampling sites during 1998
      2001, it may be concluded that a risk of contracting Lyme disease is present in
      the forest areas of north-western Poland. The highest risk of infection (9.4 % of
      infected ticks) is posed by human contact with female I. ricinus, and the risk is
      higher in late spring and early summer than in late summer and early autumn. The
      north-western part of Poland is an endemic region for B. burgdorferi s.l.

PMID- 14677909
TI  - The impact of physical work exposure on musculoskeletal symptoms among farmers
      and rural non-farmers.
AB  - In order to evaluate the impact of physical work exposure on differences in
      musculoskeletal symptom reported among Swedish farmers and referents, a cross
      sectional, population-based cohort study was performed. Male farmers (N = 1221)
      and matched non-farmers (N = 1130) were invited to take part a survey in which 76
      % participated. The analyses were based on 657 matched pairs. Lifetime incidence
      of musculoskeletal symptoms, information on work exposure, physical workload and
      leisure time physical activity were assessed by questionnaire and structured
      interview. Physical work capacity and muscle strength were measured. Farmers
      reported more low back and hip problems than the referents. After adjustment for
      the influence of work exposure factors, farmers still had a significant excess
      rate of low back and hip symptoms compared to the referents, and a significantly
      lower rate of neck and shoulder problems. In conclusion, work exposure explained
      some but not all of the farmer-referent differences in musculoskeletal symptom
      rates.

PMID- 14677910
TI  - Changes in working conditions and health among dairy farmers in southern Sweden.
      A 14-year follow-up.
AB  - The objective of this study was to describe and analyse the changes in working
      conditions and health among dairy farmers in Scania in southern Sweden during the
      period 1988-2002 by a repeat of a mail-in survey. Altogether, 83 % of the male
      and 90 % of the female dairy farmers reported some kind of symptoms in the
      musculoskeletal system during the 12 months prior to the 2002 questionnaire. This
      is an increase compared to the farmers in 1988. The highest significant changes
      were an increase of symptoms in the shoulder, neck and in the wrists/hands. The
      milkers reported most often incidental as well as persistent symptoms in the
      shoulders. The frequency of hip symptoms was significantly higher among those
      male milkers who had quit milking during the interim than for the active milkers
      in 1988. The milkers studied in 2002 had, on average, increased their working
      time per week, increased the number of cows milked as well as the use of more
      milking units. In 1988, almost all the milkers studied were working in tethering
      systems while in 2002 more than one quarter were working in loose-housing
      systems. The opinion among most of the farmers, both in 1988 and in 2002,
      regardless of age or sex, was that silage handling and the milking procedure were
      the most strenuous work operations. On the other hand, the milkers obtained their
      greatest pleasure from the actual milking job as well as from their work to
      promote the welfare of the animals. Unprofitability and great investment demands
      had a bearing on the retirement of milkers but, on the other hand, a high
      potential of the milkers could have continued 10-15 more years as dairy farmers
      if the work conditions had been better, e.g. associated with fewer health
      problems. Apart from the need for developing technical devices to facilitate the
      milking operation, further research is needed concerning the dairy farmers' well
      being and quality of life, perceived stress, and leisure time activities and how
      these and similar factors influence the prevalence of musculoskeletal symptoms.
      Strategies for preventive and intervention measures must consider physical
      workplace factors as well as personal and lifestyle characteristics.

PMID- 14677912
TI  - Two-year study of examination of blood from wild rodents for the presence of
      antiborrelian antibodies.
AB  - The aim of our work was to find the positivity rate of antibodrrelian antibodies
      (IgG) in wild-living rodents in a locality situated in north Moravia, Czech
      Republic. Results of a survey for heart rinses (172) and sera (2) antibodies to
      Borrelia burgdorferi sensu lato (s.l.) from 6 species of 174 wild rodents from
      the northern part of the Czech Republic are presented. Samples were obtained in
      2001-2002 at one locality (Studenka, 49 degrees 44', 18 degrees 05'). Host
      samples included yellow-necked mouse (Apodemus flavicollis, n = 106), wood mouse
      (A. sylvaticus, n = 170) and striped field mouse (A. agrarius, n = 13) from
      Muridae and bank vole (Clethrionomys glareolus, n = 3) and common/field vole
      (Microtus sp., n = 5) from Microtidae families. An indirect enzyme linked
      immunosorbent assay (ELISA) antibody test was used for testing heart rinses. Goat
      immunoglobulins against mouse were used as a conjugate. Antibodies to B.
      burgdorferi s.l. were found in all species. The highest positivity rate (58.8 % )
      was recorded for wood mouse (58.8 % ), bank vole (45.5 % ), and yellow-necked
      mouse (44.3 % ). Mean positivity rate for both years of collection was 43.7 %,
      mean annual positivity rate was 60.6 % in 2001, and the value of 21.3 % in 2002
      appeared significantly different. Three times as many of the Muridae as of the
      family Microtidae were caught and the actual number of seropositive Muridae was
      not significantly higher than Microtidae. Positivity of compared males and
      females was not significantly different. Results indicate that spirochaetes were
      widely represented in the northern part of the Czech Republic.

PMID- 14677911
TI  - Neurotoxic effect of dermally applied chlorpyrifos and cypermethrin.
      Reversibility of changes.
AB  - Nurelle D 550 EC preparation (Dow Elanco, USA) was applied in the study. The
      contents of biologically active substances in 1l of the preparation was: 500 g
      chlorpyrifos and 50 g of cypermethrin. The experimental studies were conducted on
      4 groups of rats (2 control - 10 animals in each group, and 2 experimental - 40
      animals in each group). The experimental groups were dermally administered a
      mixture of 27.8 mg/cm(2) of chlorpyrifos and 2.7 mg/cm(2) of cypermethrin for a
      period of 1 week and 4 weeks (4 h daily). The control groups did not participate
      in the experiment. Blood was taken from the heart after 1 day, 1 week, 2 and 3
      weeks after the administration of the preparation in order to determine
      cholinesterase activity in serum, and the brain was taken to evaluate brain
      cholinesterase activity. The brain for histologic studies was taken from rats 3
      weeks after the experiment. The cholinesterase levels in the serum and brain
      initially decrease and then return to normal at 2 and 3 weeks post-exposure,
      respectively. Slight histopathological changes in various areas of the brain as
      well as increased density of the cytoplasm in neurocytes in both experimental
      groups were observed 3 weeks post-exposure.

PMID- 14677913
TI  - Antinuclear antibodies among eastern-Polish rural inhabitants.
AB  - Rural inhabitants are exposed to considerable amounts of pesticides from water,
      soil and air. There are indications that exposure to pesticides may trigger
      production of antinuclear antibodies (ANA). Therefore, the question arises about
      the prevalence of ANA in this group. In 90 eastern-Polish rural inhabitants (RI)
      and 50 urban blood donors (BD), the presence of ANA in serum was tested using EIA
      technique (Varelisa ReCombi ANA Profile). The frequency of ANA in the RI group
      was 2.5-fold higher than in the BD group (p = 0.0175). Among RI, at least one
      autoantibody was detected in 30 % (95 % CI: 20.5-39.5 %). Most frequently, this
      was anti-dsDNA (12.2 %; 95 %CI: 5.5-19.0 %), followed by SS-A/Ro (7.8 %; 2.2-13.3
      %), RNP and Scl-70 (each 5.6 %; 0.8-10.3 %), Jo-1 (3.3 %; 0.0-7.0 %), Sm, SS
      B/La, and CENP (each 2.2 %; 0.0-5.3 %). These figures are relatively high
      compared to studies of other random populations. In the BD group, at least one
      autoantibody was found in 12 % (95 %CI: 3.0-21.0 %). Most frequently, this was
      anti-SS-A/Ro (8 %; 95 %CI: 0.5-15.5 %), followed by dsDNA, RNP, and Scl-70 (each
      2 %; 0.0-5.9 %). Neither Jo-1, Sm, SS-B/La, nor CENP-autoantibodies were found in
      this group. These figures place eastern-Polish blood donors in the middle of the
      range of prevalence observed among blood donors in other countries. The
      occurrence of antinuclear antibodies in eastern-Polish rural population is
      relatively high compared to both eastern-Polish blood donors and other random
      populations. A possible explanation for this is the long-term exposure to
      pesticides.

PMID- 14677914
TI  - Preliminary evaluation of occupational hearing loss risk among private farmers.
AB  - The article presents a preliminary evaluation of occupational hearing loss risk
      in a group of farmers selected at random and exposed to a mean annual level of
      exposure to noise L(EX,8h) = 89.1 dB. The study covered 31 family farms carrying
      out mixed production (plant-animal), possessing arable land of the size 5-40 ha,
      and equipped with the basic mechanical equipment (tractors, agricultural
      machinery, machines for production of animal fodder, workshop machinery, saws).
      Polish Standard: PN-ISO 1999:2000 was used in order to evaluate the expected
      hearing threshold among private farmers, an expected hearing loss due to noise,
      as well as risk of hearing impairment. The risk of hearing impairment was
      determined for the population of males aged 50, regularly exposed to noise for 30
      years of occupational activity, assuming as a basis for calculations the mean
      value for 3 audiometric frequencies (1, 2 and 4 kHz). The results of the study
      showed that the mean expected hearing loss (median; N(0.50)), associated only
      with noise for 50-year-old males after 30 years of employment will be: 5.5 dB
      (together with age-related loss: 14.5 dB). The risk of hearing impairment due to
      exposure to noise (for the allowable value of hearing loss: 30 dB), which may
      cause an occupational acoustic trauma, reaches the value 9.4 %. The results
      obtained confirm that noise present in the working environment of private farmers
      creates a significant risk for the organ of hearing.

PMID- 14677915
TI  - Epidemiological implications of preferences of breeding sites of mosquito species
      in Midwestern Nigeria.
AB  - The relative abundance of the aquatic stages of mosquito species distribution in
      two macrohabitats was studied between August 2001 and July 2002 using four
      different microhabitats (plastic cups, metal cans, bamboo cups and earthenware
      pots). The macrohabitats were subdivided into Areas of Derived/Secondary
      Vegetation (ADSV) and Areas of High Human Activities (AHHA). The results revealed
      mosquito species belonging to three genera (Anopheles, Culex and Aedes species),
      which are known vectors of four different human diseases (yellow fever,
      arboviruses in general, bancroftian filariasis, and malaria). Mosquito abundance
      in the three foci studied related to types of vegetation cover, amount of
      rainfall and its seasons, levels of human activities and population. Anopheles
      species were most abundant in both habitats, with a less marked effect of
      vegetation and human population. Culex species were relatively more abundant than
      Aedes in AHHA than in ADSV. Plastic containers supported 57,391 (47.4 %) and
      metal cans 42,782 (35.4 %) of larva species harvested. There is a significant
      difference in mosquito larva abundance in the two macrohabitats and different
      microhabitats studied (p < 0.05). A combination of factors account for abundant
      mosquitoes breeding in rural areas with their associated diseases implications.
      The result of the findings are discussed with respect to their public health
      implications.

PMID- 14677916
TI  - Mycological and mycotoxicological evaluation of grain.
AB  - Grain storage conditions affect its quality. In Lithuania, different types of
      farms have various harvesting, processing and storing conditions. Grain samples
      were tested from agricultural granaries of 3 different types with different grain
      storage conditions in Lithuania. During March-April in 2001 the investigation on
      mycological and mycotoxicological state of stored grain from different types of
      agricultural granaries were performed. Wheat (Triticum aestivum L.) samples (n =
      33) were tested from small, medium and large granaries. Barley (Hordeum distichon
      L.) (n = 22) was tested from small and medium granaries. Considering this issue,
      31 species of micromycetes ascribed to 8 genera were isolated and identified. The
      results obtained indicate that highest levels of micromycetes contamination are
      found in small granaries with good storing and drying equipment. Micromycetes of
      some species belonging to the Penicillium Link, Aspergillus Mich. Ex Fr.,
      Fusarium Link, and other genera, are able to produce secondary metabolites -
      mycotoxins of various compositions that are toxic to plants, animals, and humans.
      The levels of mycotoxins zearalenone and ochratoxin A were established. The
      highest concentration of zearalenone and ochratoxin A were found in grains from
      small farm granaries.

PMID- 14677917
TI  - Endotoxin exposure and lung cancer mortality by type of farming: is there a
      hidden dose-response relationship?
AB  - Previous studies have suggested that those in occupations exposed to endotoxin
      have a reduced rate of lung/respiratory cancer. An initial investigation found a
      significantly reduced risk of all sites malignant neoplasms in white male crop
      and livestock farmers, and black male and female crop farmers. This study
      provides data on lung/respiratory cancers in the same workers. Data were obtained
      from occupation and industry-coded US death certificates collected from 26 states
      for the period 1984-1993. Cause, sex, and race specific proportionate mortality
      ratios (PMRs) were calculated using a National Institute of Occupational Safety
      and Health computer program. A pooled relative risk (PRR) was obtained by summing
      up separately and then dividing the sex-race specific observed and expected
      cases, separately in crop and livestock farmers. Deaths from respiratory cancer
      were 12,482 and 2,290, and deaths from lung cancer were 12,091 and 2,201. In each
      sex and race group respiratory and lung cancer PMRs are generally lower than
      unity. Lung cancer PRR was 0.80 (0.78-0.81) in crop farmers and 0.70 (0.67-0.73)
      in livestock farmers, a significant difference (p < 0.0001). Comparison of our
      findings with those by Nieuwenhuijsen et al. [1999] reporting personal exposure
      measurements in groups of Californian farmers (endotoxin averaging 132.5 EU/m(3)
      during livestock farming against 19.9 EU/m(3) during field crop and fruit
      farming), suggests a decreasing lung cancer risk with increasing endotoxin
      exposure, and supports a possible dose-response relationship between the two.

PMID- 14677918
TI  - Concentration and species diversity of airborne fungi near busy streets in
      Lithuanian urban areas.
AB  - The investigations on air pollution in industrial cities of Lithuania: Vilnius,
      Alytus, Kaunas, Marijampole and Elektrenai were aimed at detecting the presence
      of fungi and aerosol particles during different seasons of the year. Sampling of
      fungal spores was carried out at 20 sampling sites. Active air sampling was
      performed simultaneously with the use of passive sedimentation plates. Data on
      the spread of various micromycete species in the air of cities contaminated with
      various pollutants are presented. Micromycetes of 430 species belonging to 165
      genera, 19 families, 13 orders, 4 classes, and 3 phylla were isolated and
      identified. We found 21 species, 11 genera, 7 families from Ascomycota, 6
      species, 1 genus, 1 family from Oomycota, 45 species, 15 genera, 8 families from
      Zygomycota. Mitosporic fungi comprised 138 genera, 358 species, and comprised the
      vast majority of identified species: 358 out of 430 (83.25 %). Conditionally
      pathogenic species were also isolated. It was concluded that the abundance of
      such fungi as Aspergillus niger, A. fumigatus, Cladosporium herbarum, Alternaria
      alternata, Aureobasidium pullulans in the air can be a significant criterion for
      the evaluation of air pollution.

PMID- 14677919
TI  - Exposure to bioaerosols in a municipal sewage treatment plant.
AB  - Microbiological air sampling was performed in a medium-size sewage treatment
      plant processing municipal wastewater from a city located in eastern Poland. Air
      samples for determination of the concentrations of viable mesophilic bacteria,
      Gram-negative bacteria, thermophilic actinomycetes, fungi and endotoxin were
      collected at 12 sites associated with various phases of sewage treatment process.
      The concentrations of total mesophilic bacteria (both Gram-positive and Gram
      negative) were within a range of 2.4-70.7 x 10(2) cfu/m(3). Gram-positive
      coryneform bacteria and cocci were dominant, forming respectively 56.6 % and 24.0
      % of the total count. The concentrations of Gram-negative bacteria, thermophilic
      actinomycetes, and fungi were respectively within ranges of 0.2-5.7 x 10(2)
      cfu/m(3), 0-0.5 x 10(2) cfu/m(3), and 0.24-1.4 x 10(2) cfu/m(3). Among Gram
      negative bacteria, commonly occurred Enterobacter cloacae (17.3 % of the total
      count), followed by Acinetobacter calcoaceticus (16.2 %), Pseudomonas spp. (14.0
      %) and Stenotrophomonas maltophilia (11.1 %). Among thermophilic actinomycetes
      prevailed Thermoactinomyces thalpophilus (47.2 %) and Thermoactinomyces vulgaris
      (22.2 %), while among fungi, Geotrichum candidum (32.2 %), Penicillium spp. (20
      %), Cladosporium lignicola (12.2 %), and Alternaria alternata (10.4 %).
      Altogether, 20 potentially pathogenic species or genera of bacteria and fungi
      were identified in the air samples taken in the examined plant. The values of the
      respirable fraction of airborne microflora varied within a fairly wide range and
      were between 24.1-100 %. The concentrations of airborne endotoxin were in the
      range of 0.104-5.2 ng/m(3). In conclusion, the concentrations of microorganisms
      and endotoxin in the examined municipal sewage treatment plant were low and did
      not exceed proposed occupational exposure limit values. A moderate risk for the
      workers may be associated with the presence of potentially pathogenic microbial
      species having allergenic and/or immunotoxic properties.

PMID- 14677920
TI  - Urticaceae pollen concentration in the atmosphere of North Western Spain.
AB  - Plants of the Urticaceae family can develop into a pest on soils enriched with
      nitrogen. Urticaceae pollen is a biohazard because it elicits severe pollinosis.
      Pollen grains were sampled by using a Lanzoni seven-day-recording trap from
      February 1995-December 2000 in the atmosphere of the city of Ponferrada (Leon,
      North Western Spain). The Spearman test was used to analyse the statistical
      correlation between Urticaceae pollen and certain meteorological factors in
      different main pollination periods. Maximum values are reached in June and July,
      minimum levels are recorded in January and December. The parameters bearing the
      greatest positive influence on the occurrence of Urticaceae pollen grains are:
      temperature (maximum, minimum and mean), humidity (absolute, wet-bulb
      temperature, dew point and mixing ratio) and south western wind direction;
      negative parameters are: relative humidity, rainfall and period without wind. The
      highest correlation coefficients were obtained with temperature and wet-bulb.
      Absolute humidity and wet-bulb temperature yielded better correlation than
      relative humidity; hence, these two parameters must be included in this type of
      study. The use of one main pollination period or another in statistical analysis
      has an influence on the coefficient value. The behaviour of the pollen grains in
      the atmosphere during the year also influences the results.

PMID- 14677921
TI  - Evaluation of millers' dental health. Part II. State of the parodontium.
AB  - A study of the oral health of workers in flour mills was carried out. The
      examined group consisted of 40 males and 8 females currently employed at flour
      mills. As much as 97.92 % of the workers showed evidence of parodontopathy. The
      results of the researches indicate the necessity of professional periodontal
      prophylaxis among mill workers.

PMID- 14677922
TI  - The induction of micronuclei in bovine lymphocytes by exposure to benzene and S-9
      mix.
AB  - Benzene is a widespread human carcinogen, inducing leukaemia and hematotoxicity.
      It has been shown to be a multi-organ carcinogen in animals. The effect of
      benzene was studied using induction of micronuclei (MN) in whole blood
      lymphocytes cultures after treatment with different concentrations of benzene (5,
      10, 50, 100, 500 and 1000 microM) with and without metabolic activation (S-9
      mix). A significant elevation in the induction of micronuclei was found after
      application of benzene at doses of 50 and 100 microM in both donors. Treatment of
      bovine lymphocytes did not result in the induction of micronuclei in a dose
      dependent manner. The addition of an external metabolic factor (10 % S-9 mix for
      2 h) in blood cultures treated with benzene indicated an increase of the
      genotoxic activity of benzene (at concentrations ranging from 10-100 microM).

PMID- 14677923
TI  - Prevalence of antibodies to Coxiella burnetii among farming population in eastern
      Poland.
AB  - The presence of blood serum antibodies to Coxiella burnetii phase I antigen,
      indicative of chronic Q fever or convalescence, was found by indirect immuno
      fluorescent test in 16 out of 90 examined farmers (17.8 %) living in the Lublin
      region (eastern Poland) and in none of 30 examined urban blood donors living in
      the city of Lublin (p < 0.05). In both groups no antibodies to C. burnetii phase
      II antigen, indicative of acute Q fever, were detected. The frequency of
      antibodies among farmers was greater in females than in males (26.1 % versus 9.1
      %, p < 0.05) and was significantly dependent on age ( xi(2) = 146.42, p <
      0.000001) being greatest in the subgroup of farmers aged 41-55 (38.5 %) while no
      positive reactions were found in young and elderly farmers (respectively, equal
      to or below 25 and above 56 years). The results suggest that the examined
      agricultural region could be in the past an epidemic area of Q fever, probably
      before 15-30 years.

PMID- 14677924
TI  - Molecular evidence for Anaplasma phagocytophilum and Borrelia burgdorferi sensu
      lato in Ixodes ricinus ticks from eastern Slovakia.
AB  - Ixodes ricinus ticks (20 males, 20 females and 20 nymphs) collected in Kosice,
      Slovakia were examined for the presence of Anaplasma phagocytophilum and Borrelia
      burgdorferi sensu lato (s.l.) by PCR. 38.3 % of the tested ticks carried single
      infection of B. burgdorferi s.l. and 8.3 % were infected with A. phagocytophilum.
      Double infection of both pathogens was detected in 5 % of tested ticks. These
      results indicate that both B. burgdorferi s.l. and A. phagocytophilum co
      circulate in the enzootic sites of Eastern Slovakia and may cause co-infection in
      humans.

PMID- 14677925
TI  - Identification of an HLA-A*02 restricted immunogenic peptide derived from the
      cancer testis antigen HOM-MEL-40/SSX2.
AB  - HOM-MEL-40/SSX2 is a SEREX-defined cancer testis antigen with frequent expression
      in various human neoplasms. To search for HLA-A*0201 restricted peptides that
      induce HOM-MEL-40/SSX2-specific CD8+ responses in breast cancer patients, we used
      the SYFPEITHI algorithm to identify three HOM-MEL-40/SSX2-derived nonamers with
      high binding affinity for HLA-A*0201, which has a prevalence of 40% in the
      Caucasian population. Of the three peptides, p41-49 and p103-111 but not p167-175
      had been shown to be processed by the proteasome. Only stimulation with p103-111
      induced HOM-MEL-40-specific CTLs in 5/7 patients with HOM-MEL-40/SSX2 positive
      breast cancers and in 6/11 healthy controls. HLA-A*0201 restriction of p103-111
      was demonstrated by blocking with specific antibodies. The natural processing and
      presentation of p103-111 was demonstrated by the recognition of the HOM-MEL
      40/SSX2 positive cell line SK-MEL-37 and of COS7/A2 cells transfected with HOM
      MEL-40/SSX2 by p103-111 specific CD8+ cells. No correlation was found between
      CD8+ T-cell responses against p103-111 and anti-HOM-MEL-40/SSX2 antibody titers
      in the serum of patients, suggesting that CD8+ and B-cell responses against HOM
      MEL-40/SSX2 are regulated independently. p103-111 holds promise as a broadly
      applicable peptide vaccine for patients with HOM-MEL-40/SSX2 positive neoplasms.

PMID- 14677927
TI  - Geometric disassembly of dendrimers: dendritic amplification.
AB  - Geometric disassembly of dendritic structures was realized by a cascade cleavage
      reaction triggered by an initially stimulated group at the dendrimer core.
      Release of an exponential number of dendrimer fragments was a result of the
      branching nature of the cleavage pathway. Evidence for the completion of the
      disassembly process was provided by the absorbance peak of the p-nitrophenoxide
      ion that was covalently installed at the periphery of the dendrons for this
      purpose. The release by dendrimer disassembly of an exponential number of
      dendrimer fragments that serve to alter the properties of a system is termed
      dendritic amplification.

PMID- 14677926
TI  - Rare fluctuations of native proteins sampled by equilibrium hydrogen exchange.
AB  - We present a method for determining the ensembles of native protein structures
      that result from the large fluctuations of low probability revealed by hydrogen
      exchange experiments. The measured protection factors are used to bias Monte
      Carlo simulations to sample the structures of the exchange competent species. The
      approach is illustrated by its application to the case of alpha-lactalbumin.

PMID- 14677928
TI  - Trans doubly N-confused porphyrins: Cu(III) complexation and formation of rodlike
      hydrogen-bonding networks.
AB  - A trans type of doubly N-confused isomer of NCP (trans-N2CP) was synthesized via
      N-confused fused porphyrin (NcFP). The aromatic feature of trans-N2CP due to 18pi
      electronic system is contrasted to the weak aromaticity of cis-derivative. The
      solid-state structure of trans-N2CP exhibits pi-stacking column, while the
      Cu(III) complex shows 1-D rodlike hydrogen bonding chain comparable with the
      zigzag hydrogen-bonding chain of cis-derivatives.

PMID- 14677929
TI  - Metal-stabilized phenoxonium cation.
AB  - An unprecedented metal-stabilized phenoxonium cation was prepared by a process
      involving dearomatization of a phenoxy complex. The unique eta2 C=O-metal
      (iridium) coordination mode leaves the positive charge delocalized within the
      former aromatic ring. The X-ray structure and conversion into eta2 C=O
      coordinated metal-quinone complex are described.

PMID- 14677930
TI  - Fundamental role of the fostriecin unsaturated lactone and implications for
      selective protein phosphatase inhibition.
AB  - Key derivatives and analogues of fostriecin were prepared and examined that
      revealed a fundamental role for the unsaturated lactone and confirmed the
      essential nature of the phosphate monoester. Thus, an identical 200-fold
      reduction in protein phosphatase 2A (PP2A) inhibition is observed with either the
      saturated lactone (7) or with an analogue that lacks the entire lactone (15).
      This 200-fold increase in PP2A inhibition attributable to the unsaturated lactone
      potentially may be due to reversible C269 alkylation within the PP beta12-beta13
      active site loop accounting for PP2A/4 potency and selectivity.

PMID- 14677931
TI  - Optical rotation of noncovalent aggregates.
AB  - Dilute solutions of (R)-(-)-pantolactone in CCl4 were studied by polarimetry in
      conjunction with theoretical calculations of [alpha]D. Our data demonstrate that
      the self-association of a chiral solute results in a change in [alpha]D that can
      be accounted for by the presence of hydrogen-bonded dimeric species. The
      theoretical analysis predicts a concentration-dependent specific rotation in good
      agreement with experiment. Further exploration of monomer and dimer [alpha]D
      differences, through atomic map analysis, reveals large contributions to [alpha]D
      from the hydrogen-bonded hydroxyl groups in the tightly-coupled dimer. This study
      extends the computation of chiroptical properties to the accurate concentration
      dependent prediction of [alpha]D for noncovalently interacting self-associating
      species.

PMID- 14677932
TI  - Extending lifetimes of lanthanide-based near-infrared emitters (Nd, Yb) in the
      millisecond range through Cr(III) sensitization in discrete bimetallic edifices.
AB  - A [Cr(alpha,alpha'-diimine)3]3+ chromophore is used as a donor for sensitizing
      NdIII and YbIII near-infrared (NIR) emitters in the heterobimetallic helicates
      [LnCrIIIL3]6+. The intramolecular CrIII --> LnIII energy transfer process
      controls the population of the lanthanide-centered emitting levels, thus leading
      to unprecedented extension of the NIR luminescence decay times in the millisecond
      range for Nd and Yb ions incorporated in coordination complexes.

PMID- 14677934
TI  - Using biofunctional magnetic nanoparticles to capture vancomycin-resistant
      enterococci and other gram-positive bacteria at ultralow concentration.
AB  - Covalently linked to vancomycin (Van), chemically stable and highly magnetic
      anisotropic FePt magnetic nanoparticles (3-4 nm) become water-soluble and capture
      vancomycin-resistant enterococci (VRE) and other Gram-positive bacteria at
      concentrations approximately 10(1) cfu/mL via polyvalent ligand-receptor
      interactions. When a pyramidal end of a magnet "focuses" the nanoparticles into
      approximately 1 mm(2) area, the bacteria can be observed by an optical microscope
      and further identified by electron micrograph (EM). Compared to the conventional
      use of magnetic particles (with the sizes of 1-5 microm) in biological separation
      or drug delivery, magnetic nanoparticles, combined with specific receptor-ligand
      interactions, promise a sensitive and rapid protocol to detect pathogens.

PMID- 14677933
TI  - Ageladine A: an antiangiogenic matrixmetalloproteinase inhibitor from the marine
      sponge Agelas nakamurai.
AB  - A novel MMP inhibitor, ageladine A (1) with antiangiogenic activity was isolated
      from a marine sponge Agelas nakamurai. Structure 1 was determined by a
      combination of spectroscopic and chemical methods to be an unprecedented
      structure of 4-(4,5-dibromo-1H-pyrrol-2-yl)]-1H-imidazo[4,5-c]pyridin-2-amine.

PMID- 14677935
TI  - Design of a cyclic peptide that targets a viral RNA.
AB  - The Tat protein controls transcription in lentiviruses such as HIV. A cyclic
      peptide analog of the RNA binding domain of the bovine immunodeficiency virus
      (BIV) Tat protein is shown to bind specifically to its target RNA stem loop. NMR
      data indicate a similar mode of binding of linear and cyclic peptides.

PMID- 14677936
TI  - Ligand specificity modulated by prolyl imide bond Cis/Trans isomerization in the
      Itk SH2 domain: a quantitative NMR study.
AB  - The Src homology 2 (SH2) domain of interleukin-2 tyrosine kinase (Itk) binds two
      separate ligands: a phosphotyrosine-containing peptide and the Itk Src homology 3
      (SH3) domain. Binding specificity for these ligands is regulated via cis/trans
      isomerization of the Asn 286-Pro 287 imide bond in the Itk SH2 domain. In this
      study, we develop a novel method of analyzing chemical shift perturbation and
      cross-peak volumes to measure the affinities of both ligands for each SH2
      conformer. We find that the cis imide bond containing SH2 conformer exhibits a
      3.5-fold higher affinity for the Itk SH3 domain compared with binding of the
      trans conformer to the same ligand, while the trans conformer binds
      phosphopeptide with a 4-fold greater affinity than the cis-containing SH2
      conformer. In addition to furthering the understanding of this system, the method
      presented here will be of general application in quantitatively determining the
      specificities of conformationally heterogeneous systems that use a molecular
      switch to regulate binding between multiple distinct ligands.

PMID- 14677937
TI  - Activation of N2O reduction by the fully reduced micro4-sulfide bridged
      tetranuclear Cu Z cluster in nitrous oxide reductase.
AB  - The tetranuclear CuZ cluster catalyzes the two-electron reduction of N2O to N2
      and H2O in the enzyme nitrous oxide reductase. This study shows that the fully
      reduced 4CuI form of the cluster correlates with the catalytic activity of the
      enzyme. This is the first demonstration that the S = 1/2 form of CuZ can be
      further reduced. Complementary DFT calculations support the experimental findings
      and demonstrate that N2O binding in a bent mu-1,3-bridging mode to the 4CuI form
      is most efficient due to strong back-bonding from two reduced copper atoms. This
      back-donation activates N2O for electrophilic attack by a proton.

PMID- 14677938
TI  - Role of ligand bending in the photodissociation of O2 vs CO-heme: a time
      dependent density functional study.
AB  - Time-dependent DFT calculations reveal a strong dependence of low-lying excited
      states on the <Fe-O-O angle of a model O2-heme adduct and ready access to a
      metastable side-on isomer. The predicted state crossings provide a pathway for
      internal conversion to the ground state and account for the low quantum yield for
      O2 dissociation, while the side-on isomer can account for the observation of an
      unphotolyzable fraction at low temperature. For CO-heme, the angle-sensitive
      states lie above the photoaccessed Q state and do not participate in
      photodissociation.

PMID- 14677939
TI  - An easy sonochemical route for the encapsulation of tetracycline in bovine serum
      albumin microspheres.
AB  - A one-step sonochemical process starting with the native BSA and tetracycline was
      employed to encapsulate the antibiotic drug in microspheres of BSA. The
      tetracycline loading studies showed that the maximum tetracycline loading
      capacity was found to be 65%. The antimicrobial activity of the tetracycline
      loaded in BSA microspheres was demonstrated on two bacterial strains that are
      sensitive to tetracycline.

PMID- 14677940
TI  - Infrared spectroscopy of neutral C7H7 isomers: benzyl and tropyl.
AB  - The gas-phase infrared absorption spectra of neutral benzyl and tropyl, isomers
      of formula C7H7, have been measured in the 400-1800 cm-1 spectral region. In
      addition, a quantum chemical calculation has been performed to model the infrared
      spectra. For the benzyl radical, the theory shows satisfactory overlap with the
      experiment, although vibrations involving the CH2 group might be anharmonic. The
      tropyl radical, which is subject to the Jahn-Teller effect, seems well modeled
      for the out-of-plane vibrational modes, but less so for the in-plane vibrational
      modes.

PMID- 14677941
TI  - The structures of vanadium oxide cluster-ethene complexes. A combined IR multiple
      photon dissociation spectroscopy and DFT calculation study.
AB  - Infrared spectra of complexes of small vanadium oxide clusters with ethene are
      determined using infrared multiple photon dissociation (IR-MPD) spectroscopy in
      the range of 550-1850 cm-1. The structures of the complexes have been identified
      by comparison of the experimental spectra with the harmonic vibrational
      frequencies and corresponding IR intensities of possible isomers calculated with
      DFT methods. We find that the ethene molecule binds directly to a vanadium atom
      in the cluster, although this it is not in all cases the most stable arrangement.

PMID- 14677942
TI  - Large-scale synthesis of single-crystalline perovskite nanostructures.
AB  - Single-crystalline perovskite nanostructures with reproducible shape have been
      prepared using a simple, readily scaleable solid-state reaction in the presence
      of NaCl and a nonionic surfactant. Pristine BaTiO3 nanowires have diameters
      ranging from 50 to 80 nm with an aspect ratio larger than 25. Single-crystalline
      SrTiO3 nanocubes with a mean edge length of 80 nm have been produced using a
      similar procedure.

PMID- 14677943
TI  - Amplified nucleic acid sensing using programmed self-cleaving DNAzyme.
AB  - A newly designed target-assisted self-cleavage (TASC) probe composed of a target
      binding site and a DNAzyme domain undergoes TASC when activated via hybridization
      with a target DNA/RNA. This self-splicing or self-dissociation reaction occurs in
      a catalytic manner with the probe as a substrate and the target as a catalyst,
      since the fragmented products are automatically released from the target, thus
      amplifying the sequence information of the latter under non-PCR, i.e., isothermal
      and enzyme/reagent-free, conditions. A fluorescence-reporting TASC probe having a
      fluorescein/dabsyl FRET pair across the cleavage site allows a mix-and-read
      discrimination of single-nucleotide differences in the target.

PMID- 14677944
TI  - A novel supramolecular multicolor thermometer by self-assembly of a pi-extended
      zinc porphyrin complex.
AB  - A zinc complex of (3-pyridyl)porphyrin with an alkynyl sidearm (1) preferentially
      formed a cyclic tetramer in toluene, which showed supramolecular thermochromism
      at ambient temperatures of 0-100 degrees C. Because of an appropriate extension
      of pi-electronic conjugation of the porphyrin chromophore, the thermal-induced
      self-assembling dynamics of 1 can be detected as a vivid color change from red to
      yellow to green. In sharp contrast, 2 without any alkynyl group, on heating,
      developed only a small color change from orange to pink, while 3 bearing two
      alkynyl groups stayed green and did not display any thermochromism.

PMID- 14677945
TI  - Application of NMR SHAPES screening to an RNA target.
AB  - Several NMR screening techniques have been developed in recent years to aid in
      the identification of lead drug compounds. These NMR methods have traditionally
      been used for protein targets, and here we examine their applicability for an RNA
      target. We used the SHAPES compound library to test three different NMR screening
      methodologies: the saturation transfer difference (STD), the 2D trNOESY, and the
      WaterLOGSY experiments. We found that the WaterLOGSY experiment was the most
      sensitive method for our RNA target, the P4P6 domain of the Tetrahymena
      thermophila Group I intron. Using the WaterLOGSY experiment, we found that 23 of
      the 112 SHAPES compounds interact with P4P6. To identify which of these 23 hits
      bind through nonspecific interactions, we counterscreened with a linear duplex
      RNA control and identified one of the SHAPES compounds as interacting with P4P6
      specifically. We thus demonstrated that the WaterLOGSY experiment in combination
      with the SHAPES compound library can be used to efficiently find RNA binding lead
      compounds.

PMID- 14677946
TI  - Stereochemically controlled PMMA-exfoliated silicate nanocomposites using
      intergallery-anchored metallocenium cations.
AB  - Representative C2v-, C2-, and Cs-symmetric metallocene complexes were effectively
      anchored inside the silicate galleries via a non-cation-exchange approach
      involving protonolysis. These intergallery-anchored metallocenium cations allow
      for the first synthesis of in situ polymerized nanocomposites comprising
      exfoliated silicate nanoplatelets homogeneously dispersed in the atactic,
      isotactic, or syndiotactic PMMA matrixes.

PMID- 14677947
TI  - Collagen-protein interactions mapped by phototriggered thiol introduction.
AB  - Accumulating evidence shows that collagen plays important roles in many
      biological systems by interacting with various proteins. The major limitation to
      determining protein-binding sites on collagen has been a lack of useful methods.
      We have developed a new strategy for mapping these sites using a photoreactive
      cross-linker, APDP. A unique -SH group can be introduced into collagen in the
      vicinity of the protein-binding sites by DTT reduction of the SS bond in the
      cross-linked product. To identify the sites of cross-linking in collagen, the
      strategy used was as follows: (i) derivatization of the free -SH group with
      fluorescein-5-maleimide (FM); (ii) fragmentation of collagen with an appropriate
      collagenase; (iii) separation of FM-labeled fragments by two-dimensional diagonal
      electrophoresis; and (iv) detection of cross-linked partners of collagen-binding
      protein as fluorescent spots under UV light. This strategy can be used to
      determine the binding sites of various proteins on collagen.

PMID- 14677948
TI  - Mechanistic diversity of fosfomycin resistance in pathogenic microorganisms.
AB  - Microbial resistance to the antibiotic fosfomycin [(1R,2S)-epoxypropylphosphonic
      acid, 1] is known to be mediated by thiol transferase enzymes FosA and FosB,
      which catalyze the addition of glutathione and l-cysteine to C1 of the oxirane,
      respectively. A probe of the microbial genome database reveals a related group of
      enzymes (FosX). The genes mlr3345 from Mesorhizobium loti and lmo1702 from
      Listeria monocytogenes were cloned and the proteins expressed. This heretofore
      unrecognized group of enzymes is shown to catalyze the Mn(II)-dependent addition
      of water to C1 of the oxirane. The ability of each enzyme to confer resistance in
      Escherichia coli is correlated with their catalytic efficiency, such that the M.
      loti protein confers low resistance while the Listeria enzyme confers very robust
      resistance. The crystal structure of the FosX from M. loti was solved at a
      resolution of 1.83 A. The structure reveals an active-site carboxylate (E44)
      located about 5 A from the expected position of the substrate that appears to be
      poised to participate in catalysis. Single turnover experiments in H218O and
      kinetic analysis of the E44G mutant of the FosX enzymes indicate that the
      carboxylate of E44 acts as a general base in the direct addition of water to 1.
      The FosX from M. loti also catalyzes the addition of glutathione to the
      antibiotic. The catalytic promiscuity and low efficiency of the M. loti protein
      suggest that it may be an intermediate in the evolution of clinically relevant
      fosfomycin resistance proteins such as the FosX from Listeria monocytogenese.

PMID- 14677949
TI  - Long-distance radical cation migration in duplex DNA: the effect of contiguous
      A.A and T.T mismatches on efficiency and mechanism.
AB  - A series of DNA oligomers was prepared. Each oligomer contained an anthraquinone
      group (AQ, sensitizer) covalently linked at a 5'-end and two GG steps that
      surrounded a variable region. The variable region was composed of A.T base pairs
      or A.A or T.T mismatches. Irradiation of the AQ injected a radical cation (hole)
      into the DNA that migrated through the duplex, being trapped by reaction with H2O
      of O2 at the GG steps. The effect of substituting A.A or T.T mismatches for
      Watson-Crick base pairs was examined. For A.A mispairs, charge transfer through
      the mismatch region was as efficient as through normal DNA. For the T.T
      mismatches, radical cation transport was strongly distance-dependent. These
      findings suggest that A.A mismatches form a zipper-like motif, and charge
      transport proceeds by a hopping mechanism. In contrast, charge transport through
      the T.T mismatches (where there are no purines) may proceed by quantum mechanical
      tunneling.

PMID- 14677950
TI  - Evidence for alkane coordination to an electron-rich uranium center.
AB  - A series of five uranium-alkane complexes of the general formula
      [(ArO)3tacn)U(alkane)].(cy-alkane) has been synthesized and crystallographically
      characterized. In all cases, X-ray diffraction studies revealed a pseudo-six
      coordinate trivalent uranium core structure, [(ArO)3tacn)U], with a coordinated
      alkane ligand at the axial position. The average U-C bond distance to the bound
      alkane was determined to be 3.798 A, which is considerably shorter than the sum
      of the van der Waals radii of the U atom and a CH2 or CH3 unit (3.9 A). In all
      complexes, the alkane is coordinated in an eta2-H,C fashion.

PMID- 14677951
TI  - Semiconductor quantum dots for photodynamic therapy.
AB  - The applicability of semiconductor QDs in photodynamic therapy (PDT) was
      evaluated by studying the interaction between CdSe QDs with a known silicon
      phthalocyanine PDT photosensitizer, Pc4. The study revealed that the QDs could be
      used to sensitize the PDT agent through a fluorescence resonance energy transfer
      (FRET) mechanism, or interact directly with molecular oxygen via a triplet energy
      transfer process (TET). Both mechanisms result in the generation of reactive
      singlet oxygen species that can be used for PDT cancer therapy.

PMID- 14677952
TI  - Electrochemical generation of c 60 2+ and c 60 3+.
AB  - The adoption of suitable experimental conditions, which comprise ultra-dry
      solvents and electrolytes with very high oxidation resistance and low
      nucleophilicity, has allowed observation, for the first time, of the cyclic
      voltammetric reversible generation of C602+ and C603+. The present study adds
      valuable information on the still relatively unknown properties of these
      important all-carbon carbocations and, in view of their very high reactivity,
      offers new possible routes for fullerene functionalization.

PMID- 14677953
TI  - 1H-1H dipolar couplings provide a unique probe of RNA backbone structure.
AB  - A NMR method is described that permits simultaneous measurement of the geminal
      2JH1H2 + 2DH1H2 splitting and the sum of the 1JCH1 + 1DCH1 + 1JCH2 + 1DCH2
      couplings for methylene groups, where 2DH1H2 and 1DCH are residual dipolar
      couplings, occurring when molecules are weakly oriented relative to the magnetic
      field. By suppressing either the upfield or downfield half of the 1H-1H geminal
      doublet, the experiment yields improved resolution relative to regular two
      dimensional 1H-13C correlation spectra, making it applicable to systems of
      considerable complexity. The method is demonstrated for measurement of all
      2DH5'H5'' couplings in a 24-nucleotide 13C-enriched RNA stem loop structure,
      weakly aligned in liquid crystalline Pf1. The method is equally applicable to
      methylene groups in 13C-labeled proteins and to natural abundance samples of
      smaller molecules.

PMID- 14677954
TI  - Chiral bisphosphine BINAP-stabilized gold and palladium nanoparticles with small
      size and their palladium nanoparticle-catalyzed asymmetric reaction.
AB  - The reduction of tetrachloroaurate or potassium tetrachloropalladate with sodium
      borohydride in the presence of optically active 2,2'-bis(diphenylphosphino)-1,1'
      binaphthyl [BINAP] gave the chiral (S)- or (R)-BINAP-stabilized gold or palladium
      nanoparticles which showed the small core (1.7 nm for BINAP-Au and 2.0 nm for
      BINAP-Pd) with narrow size distribution and remarkably high stability. Asymmetric
      hydrosilylation of styrene with trichlorosilane in the presence of chiral BINAP
      Pd nanoparticles afforded an optically active 1-phenyl-1-trichlorosilylethane
      which was converted into an optically active 1-phenylethanol (95% enantiomeric
      excess) by oxidative cleavage of the carbon-silicon bond.

PMID- 14677955
TI  - Versatile synthesis of small NLO-active molecules forming amorphous materials
      with spontaneous second-order NLO response.
AB  - A novel synthetic approach to a series of bulky triarylamines substituted by
      various electron-withdrawing groups and forming amorphous materials is presented.
      Under vacuum evaporation, thin films with high optical quality are obtained and
      exhibit spontaneous second-order nonlinear optical activity. This unprecedented
      result is likely due to subtle balance between strong dipole-dipole interactions
      and steric crowding causing self-assembly and noncentrosymmetric local ordering,
      stable up to one year.

PMID- 14677956
TI  - Synthesis of (3S,5R)-carbapenam-3-carboxylic acid and its role in carbapenem
      biosynthesis and the stereoinversion problem.
AB  - (5R)-Carbapenem-3-carboxylic acid is the simplest structurally among the
      naturally occurring carbapenem beta-lactam antibiotics. It is the produced from
      (3S,5S)-carbapenam-3-carboxylic acid utilizing a remarkable
      stereoinversion/desaturation process by CarC (carbapenem synthase), an alpha
      ketoglutarate dependent non-heme iron oxygenase. In this communication, we
      demonstrate for the first time that the epimeric (3S,5R)-carbapenam-3-carboxylic
      acid is an intermediate in the overall catalytic cycle to the carbapenem
      antibiotic. The role of alpha-ketoglutarate in the stereoinversion and
      desaturation processes is also examined.

PMID- 14677957
TI  - Catalytic enantioselective iodocyclization of gamma-hydroxy-cis-alkenes.
AB  - Enantioselective iodocyclization of gamma-hydroxy-cis-alkenes has been achieved
      using I2 in the presence of an unprecedented catalyst system generated from (R,R)
      t-Bu-salen-Co(II) complex and NCS to produce 2-monosubstituted tetrahydrofurans
      up to 90% ee. While NCS turned out to be the essential additive, neither (R,R)
      salen-Co(II) nor (R,R)-salen-Co(III) by itself is likely to be the active species
      responsible for the asymmetric intramolecular iodoetherification.

PMID- 14677958
TI  - Direct observation of Calpha-Halpha...O=C hydrogen bonds in proteins by
      interresidue h3JCalphaC' scalar couplings.
AB  - The role of C-H...O hydrogen bonds in the stabilization of biomolecules is
      increasingly being recognized from the evidence of close C-H...O contacts in
      crystal structures. However, relatively little is known about their strength.
      Here, we report the observation of NMR scalar couplings (h3JCalphaC') between the
      two carbons on each side of Calpha-Halpha...O=C H-bonds in proteins. These
      couplings give direct evidence of the correlation of the electronic wave
      functions in the donor and acceptor groups of Calpha-Halpha...O=C H-bonds. A long
      range H(NCO)CA experiment or a selective long-range H(NCA)CO experiment was used
      for the detection of h3JCalphaC' correlations in the beta-sheet regions of the
      immunoglobulin binding domain of protein G. In total, six such correlations were
      detectable. These correspond to half of the Calpha-Halpha...O=C H-bonds of
      protein G with Halpha...O distances shorter than 2.5 A. The h3JCalphaC' couplings
      range from 0.2 to 0.3 Hz and are in good agreement with predicted average values
      based on DFT/FPT calculations. An anticorrelation is observed with the size of
      h3JNC' coupling constants across N-HN...O=C H-bonds, which share the same
      acceptor carbonyl oxygen.

PMID- 14677959
TI  - N=N bond cleavage by a low-coordinate ironII hydride complex.
AB  - Reaction of the three-coordinate complex LFeCl (L = bulky beta-diketiminate) with
      KBEt3H gives a dark red iron(II) hydride complex. The complex is a dimer in the
      solid state, but spectroscopy and kinetics suggest that an orange three
      coordinate monomer is in equilibrium with the dimer in solution. The double bond
      of azobenzene is completely cleaved by heating with the hydride complex, and a
      hydrazido intermediate can be isolated.

PMID- 14677960
TI  - Synthesis of monodisperse superparamagnetic Fe/silica nanospherical composites.
AB  - A new method for the synthesis of monodisperse superparamagnetic nanospherical
      composites with a core containing metallic alpha-Fe nanocrystals dispersed in a
      silica matrix, and a shell only containing silica, is reported. Essential to the
      formation of this microstructure is to work with lamellar-like structures in
      conditions close to the upper-phase boundary limit for formation of
      microemulsions, and to control the solubility and pH of the metallic precursors.
      An advantage of the method is its versatility, which allows us to change the
      particle size (both for the nanomagnets and for the composite) and the spatial
      arrangement of the nanomagnets in the matrix. Our results indicate that this
      material could be adequate for biotechnology applications.

PMID- 14677961
TI  - Adsorption states and modifier-substrate interactions on Pt(111) relevant to the
      enantioselective hydrogenation of alkyl pyruvates in the Orito reaction.
AB  - Reflectance FTIR spectroscopy (RAIRS) was used to study the chemisorption and
      intermolecular interactions of methyl pyruvate and (+/-)-1-(1-naphthyl)ethylamine
      (NEA) on Pt(111). NEA serves, in this study, as a tractable model of a chiral
      modifier in the asymmetric hydrogenation of alpha-dicarbonyls on alkaloid
      modified platinum surfaces-the Orito reaction. The results show the presence of a
      majority enediolate state on the clean surface. A perpendicularly adsorbed trans
      conformation state is populated at close to full-monolayer coverage on the clean
      surface. The latter state desorbs at 185 K. The enediolate undergoes dissociation
      at 230 K. NEA displays hydrogen-bond association at high coverages. Coadsorption
      studies show that NEA inhibits the formation of the enediolate state. Multilayer
      methyl pyruvate shows a clear hydrogen-bond interaction with chemisorbed NEA,
      leading to a reorientation of the ethylamine group. The high-coverage trans
      chemisorbed methyl pyruvate state also hydrogen-bonds to chemisorbed NEA. The
      latter interaction renders the trans state stable to above 300 K. A new schematic
      mechanism for the Orito reaction is proposed on the basis of these data.

PMID- 14677962
TI  - Formation of surface CN from the coupling of C and N atoms on Pt(111).
AB  - Reflection absorption infrared spectroscopy (RAIRS) and temperature-programmed
      desorption have been used to study the coupling of C and N atoms on Pt(111) to
      form surface CN. This reaction underlies the important synthesis of HCN from
      methane and ammonia over platinum catalysts. Since CH4 and NH3 do not thermally
      dissociate on Pt(111) under ultrahigh vacuum conditions, we used CH3I and
      electron bombardment of NH3 to generate reactive surface species. Surface CN is
      formed at a temperature of 500 K from surface Nads and Cads atoms. The presence
      of surface CN is detected by HCN desorption and through the reaction of hydrogen
      with CNads to form a surface >CNH2 (aminocarbyne) species, which has a
      characteristic RAIR spectrum.

PMID- 14677963
TI  - Rhenium-catalyzed coupling of propargyl alcohols and allyl silanes.
AB  - A mild method for the regioselective coupling of propargyl alcohols and
      allylsilanes is described. The method employs an air- and moisture-tolerant
      rhenium-oxo complex ((dppm)ReOCl3) as a catalyst for the formation of sp3-carbon
      sp3-carbon bonds without the need for prior activation of the propargyl alcohol
      as a halide or pseudohalide. The stability of the high oxidation state rhenium
      complex allows for simple reisolation and reuse of the catalyst. A broad range of
      functional groups is tolerated including aryl halides, olefins, esters, and acid
      labile functional groups such as acetals. Furthermore, displacement of the
      alcohol occurs preferentially even in the presence of other electrophiles such as
      primary alkyl halides and conjugated esters. The use of enantiopure crotylsilanes
      as coupling partners allows for the asymmetric construction of two adjacent
      stereocenters. The potential of this reaction is demonstrated in an asymmetric
      synthesis of delta-lactone, di-O-methylcalopin.

PMID- 14677964
TI  - Ruthenium-catalyzed aromatization of aromatic enynes via the 1,2-migration of
      halo and aryl groups: a new process involving electrocyclization and skeletal
      rearrangement.
AB  - The halo and aryl substituents of the 1,2-disubstituted styryl group of aromatic
      enynes undergo a 1,2-shift in the aromatization reaction catalyzed by
      TpRuPPh3(CH3CN)2PF6 (10 mol %) in toluene (110 degrees C, 6-8 h). The aryl group
      shifts to the neighboring olefin carbon, and the iodo (or bromo) substituent
      migrates to the terminal alkyne carbon. The mechanisms of these two migrations
      have been elucidated by isotope labeling experiments. It indicates that the 1,2
      aryl shift arises from 5-endo-dig electrocyclization of a ruthenium-vinylidene
      species, whereas the 1,2-iodo shift follows a 6-endo-dig pathway.

PMID- 14677965
TI  - Quantifying the effects of deuterium substitution on phospholipid mixing in
      bilayer membranes. A nearest-neighbor recognition investigation.
AB  - Nearest-neighbor recognition measurements have established that the effects of
      deuterium substitution on phospholipid mixing are exceedingly small. Thus, the
      mixing behavior of an exchangeable phospholipid bearing two stearoyl chains with
      a homologue containing two myristoyl chains in gel-fluid bilayers, fluid
      bilayers, cholesterol-rich fluid bilayers, and gel-fluid bilayers that have been
      enriched with cholesterol correspond to a difference in the free energy of mixing
      that is less than 2.2 cal/mol of hydrogen in all cases. These findings provide
      the strongest evidence to date in support of the use of deuterated phospholipids
      as "nonperturbing" probes for structural and dynamic studies of bilayer
      membranes.

PMID- 14677966
TI  - Methyl side-chain dynamics in proteins using selective enrichment with a single
      isotopomer.
AB  - 13C relaxation studies on side-chain methyl groups in proteins typically involve
      measurements on (13)CHD(2) isotopomers, where the (13)C relaxation mechanism is
      particularly straightforward in the presence of a single proton. While such
      isotopomers can be obtained in proteins overexpressed in bacteria by use of (13)C
      enriched and fractionally deuterated media, invariably all possible (2)H
      isotopomers are obtained. This results in a loss of both resolution and
      sensitivity, which becomes particularly severe for larger proteins. We describe
      an approach that overcomes this problem by chemical synthesis of amino acids
      containing a pure (13)CHD(2) isotopomer. We illustrate the benefits of this
      approach in (13)C side-chain relaxation measurements on the mouse major urinary
      protein selectively enriched with [gamma(1),gamma(2)
      (13)C(2),alpha,beta,gamma(1),gamma(1),gamma(2),gamma(2)-(2)H(6)] valine.
      Relaxation measurements in the absence and presence of pyrazine-derived ligands
      suggest that valine side-chain dynamics do not contribute significantly to
      binding entropy.

PMID- 14677967
TI  - Nitrogen binding to the FeMo-cofactor of nitrogenase.
AB  - Density functional calculations are presented to unravel the first steps of
      nitrogen fixation of nitrogenase. The individual steps leading from the resting
      state to nitrogen binding at the FeMo-cofactor with a central nitrogen ligand are
      characterized. The calculations indicate that the Fe-Mo cage opens as dinitrogen
      binds to the cluster. In the resting state, the central cage is overall neutral.
      Electrons and protons are transferred in an alternating manner. Upon dinitrogen
      binding, one protonated sulfur bridge is broken. An axial and a bridged binding
      mode of dinitrogen have been identified. Adsorption at the Mo site has been
      investigated but appears to be less favorable than binding at Fe sites.

PMID- 14677968
TI  - Active species of horseradish peroxidase (HRP) and cytochrome P450: two
      electronic chameleons.
AB  - The active site of HRP Compound I (Cpd I) is modeled using hybrid density
      functional theory (UB3LYP). The effects of neighboring amino acids and of
      environmental polarity are included. The low-lying states have porphyrin radical
      cationic species (Por(*)(+)). However, since the Por(*)(+) species is a very good
      electron acceptor, other species, which can be either the ligand or side chain
      amino acid residues, may participate in electron donation to the Por(*)(+)
      moiety, thereby making Cpd I behave like a chemical chameleon. Thus, this
      behavior that was noted before for Cpd I of P450 is apparently much more wide
      ranging than initially appreciated. Since chemical chameleonic behavior property
      was found to be expressed not only in the properties of Cpd I itself, but also in
      its reactivity, the roots of this phenomenon are generalized. A comparative
      discussion of Cpd I species follows for the enzymes HRP, CcP, APX, CAT
      (catalase), and P450.

PMID- 14677969
TI  - Model systems for flavoenzyme activity: relationships between cofactor structure,
      binding and redox properties.
AB  - A series of flavins were synthesized bearing electron-withdrawing and -donating
      substituents. The electrochemical properties of these flavins in a nonpolar
      solvent were determined. The recognition of these flavins by a diamidopyridine
      (DAP) receptor and the effect this receptor has on flavin redox potential was
      also quantified. It was found that the DAP-flavin binding affinity and the
      reduction potentials (E(1/2)) for both the DAP-bound and unbound flavins
      correlated well with functions derived from linear free energy relationships
      (LFERs). These results provide insight and predictive capability for the
      interplay of electronics and redox state-specific interactions for both abiotic
      and enzymatic systems.

PMID- 14677970
TI  - Synthetic enantiopure aziridinomitosenes: preparation, reactivity, and DNA
      alkylation studies.
AB  - An enantiocontrolled route to aziridinomitosenes had been developed from l-serine
      methyl ester hydrochloride. The tetracyclic target ring system was assembled by
      an internal azomethine ylide cycloaddition reaction based on silver ion-assisted
      intramolecular oxazole alkylation and cyanide-induced ylide generation via a
      labile oxazoline intermediate (62 to 66). Other key steps include reductive
      detritylation of 26, methylation of the N-H aziridine 56, oxidation of the
      sensitive cyclohexenedione 68 to quinone 70, and carbamoylation using Fmoc-NCO.
      Although the aziridinomitosene tetracycle is sensitive, a range of protecting
      group manipulations and redox chemistry can be performed if suitable precautions
      are taken. A study of DNA alkylation by the first C-6,C-7-unsubstituted
      aziridinomitosene 11a has been carried out, and evidence for DNA cross-link
      formation involving nucleophilic addition to the quinone subunit is described.

PMID- 14677971
TI  - NMR spectra of a microcrystalline protein at 30 kHz MAS.
AB  - Proteins are not always available in amounts desirable for solid-state magic
      angle spinning (MAS) nuclear-magnetic resonance (NMR) spectroscopy. To maximize
      the signal-to-noise ratio achievable with small samples, the filling factor must
      be optimized by using small-diameter MAS rotors. These rotors have the added
      benefit of allowing higher radio frequency field amplitudes during polarization
      transfer steps and during decoupling periods as well as allowing higher spinning
      frequencies. We demonstrate the advantages of relatively fast MAS (30 kHz using a
      2.5 mm rotor) compared to MAS at 12 kHz for the 10.4 kDa model protein Crh with
      93 residues and show that the signal-to-noise ratio in two-dimensional
      correlation spectra can be significantly improved by taking advantage of
      optimized pulse sequences available with rapid MAS.

PMID- 14677972
TI  - DNA-templated dimerization of hairpin polyamides.
AB  - Double-helical DNA accelerates the rate of ligation of two six-ring hairpin
      polyamides which bind adjacent sites in the minor groove via a 1,3-dipolar
      cycloaddition to form a tandem dimer. The rate of the templated reaction is
      dependent on DNA sequence as well as on the distance between the hairpin-binding
      sites. The tandem dimer product of the DNA-templated reaction has improved
      binding properties with respect to the smaller hairpin fragments. Since cell and
      nuclear uptake of DNA-binding polyamides will likely be dependent on size, this
      is a minimum first step toward the design of self-assembling small gene
      regulating fragments to produce molecules of increasing complexity with more
      specific genomic targeting capabilities.

PMID- 14677973
TI  - Variable coordination geometries at the diiron(II) active site of ribonucleotide
      reductase R2.
AB  - The R2 subunit of Escherichia coli ribonucleotide reductase contains a dinuclear
      iron center that generates a catalytically essential stable tyrosyl radical by
      one electron oxidation of a nearby tyrosine residue. After acquisition of Fe(II)
      ions by the apo protein, the resulting diiron(II) center reacts with O(2) to
      initiate formation of the radical. Knowledge of the structure of the reactant
      diiron(II) form of R2 is a prerequisite for a detailed understanding of the O(2)
      activation mechanism. Whereas kinetic and spectroscopic studies of the reaction
      have generally been conducted at pH 7.6 with reactant produced by the addition of
      Fe(II) ions to the apo protein, the available crystal structures of diferrous R2
      have been obtained by chemical or photoreduction of the oxidized diiron(III)
      protein at pH 5-6. To address this discrepancy, we have generated the diiron(II)
      states of wildtype R2 (R2-wt), R2-D84E, and R2-D84E/W48F by infusion of Fe(II)
      ions into crystals of the apo proteins at neutral pH. The structures of diferrous
      R2-wt and R2-D48E determined from these crystals reveal diiron(II) centers with
      active site geometries that differ significantly from those observed in either
      chemically or photoreduced crystals. Structures of R2-wt and R2-D48E/W48F
      determined at both neutral and low pH are very similar, suggesting that the
      differences are not due solely to pH effects. The structures of these "ferrous
      soaked" forms are more consistent with circular dichroism (CD) and magnetic
      circular dichroism (MCD) spectroscopic data and provide alternate starting points
      for consideration of possible O(2) activation mechanisms.

PMID- 14677975
TI  - Catalytic asymmetric Michael reaction of beta-keto esters: effects of the linker
      heteroatom in linked-BINOL.
AB  - We describe the development of a general catalytic asymmetric Michael reaction of
      acyclic beta-keto esters to cyclic enones, in which asymmetric induction occurs
      at the beta-position of the acceptors. Among the various asymmetric catalyst
      systems examined, the newly developed La-NR-linked-BINOL complexes (R = H or Me)
      afforded the best results in terms of reactivity and selectivity. In general, the
      NMe ligand 2 was suitable for the combination of small enones and small beta-keto
      esters, and the NH ligand 1 was suitable for bulkier substrates (steric tuning of
      the catalyst). Using the La-NMe-linked-BINOL complex, the Michael reaction of
      methyl acetoacetate (8a) to 2-cyclohexen-1-one (7b) gave the corresponding
      Michael adduct 9ba in 82% yield and 92% ee. The linker heteroatom in linked-BINOL
      is crucial for achieving high reactivity and selectivity in the Michael reaction
      of beta-keto esters. The amine moiety in the NR-linked-BINOL can also tune the
      Lewis acidity of the central metal (electronic tuning of the catalyst), which was
      supported by density functional studies and experimental results. Another
      advantage of the NR-linked-BINOL ligand as compared with O-linked-BINOL is the
      ease of modifying a substituent on the amine moiety, making it possible to
      synthesize a variety of NR-linked-BINOL ligands for further improvement or
      development of new asymmetric catalyses by introducing additional functionality
      on the linker with the amine moiety. The efficiency of the present asymmetric
      catalysis was demonstrated by the synthesis of the key intermediate of (-)
      tubifolidine and (-)-19,20-dihydroakuammicine in only five steps compared to the
      nine steps required by the original process from the Michael product of malonate.
      This strategy is much more atom economical. On the basis of the results of
      mechanistic studies, we propose that a beta-keto ester serves as a ligand as well
      as a substrate and at least one beta-keto ester should be included in the active
      catalyst complex. Further improvement of the reaction by maintaining an
      appropriate ratio of the La-NMe-linked-BINOL complex and beta-keto esters is also
      described.

PMID- 14677974
TI  - Sensitive high resolution inverse detection NMR spectroscopy of proteins in the
      solid state.
AB  - A new indirect detection scheme for obtaining (15)N/(1)H shift correlation
      spectra in crystalline proteins is described. Excellent water suppression is
      achieved without the need for pulsed field gradients, and using only a 2-step
      phase cycle. Careful attention to overall NMR instrument stability was found
      critical for obtaining the best resolution and sensitivity. Magnetic dilution by
      deuteration of the protein in combination with high-speed magic angle spinning
      produces (1)H resonances averaging only 0.22 ppm in width, and in some cases
      lines as narrow as 0.17 ppm are obtained. In application to two different
      polymorphs of ubiquitin, structure dependent differences in both (15)N and (1)H
      amide chemical shifts are observed. In one case, distinct shifts for different
      molecules in the asymmetric unit are seen, and all differ substantially from
      solution NMR shifts. A gain of 7 in sensitivity makes the method competitive with
      solution NMR as long as nanocrystalline samples are available.

PMID- 14677976
TI  - HYSCORE spectroscopy in the cytochrome b(559) of the photosystem II reaction
      center.
AB  - A HYSCORE investigation of the heme center in the cytochrome b(559) is presented.
      To assign the observed signals to specific nuclei, bis-imidazol coordinated heme
      compounds that model the iron environment in cytochrome b(559) are also studied.
      In the model compounds selective isotopic substitution of nitrogen atoms has been
      performed. The HYSCORE spectra allow us to obtain the hyperfine and quadrupolar
      coupling tensors of heme and imidazol bonding nitrogen atoms. The results can be
      interpreted in terms of the structure and the electronic distribution of the
      active center. The hyperfine tensors indicate that the unpaired electron is
      confined in a nonbonding iron orbital with a negligible nitrogen p orbital
      contribution. Quadrupolar coupling tensors suggest that the orientation of the
      semioccupied orbital is driven by the orientation of the two parallel imidazol
      rings of the axial histidine side chains. The results are discussed in terms of
      the structure-function relationship of cytochromes.

PMID- 14677977
TI  - Conformational behavior of beta-proline oligomers.
AB  - Conformations of the monomer, dimer, and hexamer of beta-proline ((S) pyrrolidine
      3-carboxylic acid) were determined using ab initio molecular orbital calculations
      at the RHF/6-31G level of theory. The calculated minima are in good agreement
      with experimental data for the system and imply that the conformations could be
      controlled through chemical modification at Calpha, Cgamma, or Cdelta. The
      monomer and dimer are small and flexible with many low-energy minima. In the
      hexamer, two forms of regular secondary structure are preferred: left-handed
      helices with cis-peptide bonds and right-handed helices with trans-peptide bonds.
      This is similar to the behavior of alpha-proline helices, except that the
      relationship between the peptide rotamer and the handedness of the helix is
      reversed. Therefore, helices of the enantiomer of beta-proline ((R)-pyrrolidine-3
      carboxylic acid) should exhibit the same behavior as alpha-proline helices.
      Through understanding the conformational behavior of beta-proline in various
      environments, it may be possible to use these protein mimics to inhibit various
      protein-protein recognition events. To estimate these effects, SCRF energies for
      the conformers were determined in dielectrics corresponding to water, methanol,
      and chloroform. It appears that the cis helices are more favorably solvated than
      the trans helices, but the cause is not clear.

PMID- 14677978
TI  - Spectroscopic evidence for a persistent benzenium cation in zeolite H-beta.
AB  - Experimental evidence of protonation of an aromatic ring by a zeolite is hereby
      presented for the first time. The changes in vibrational properties and
      electronic transitions of the highest polymethylbenzene homologue, that is,
      hexamethylbenzene, were investigated after introducing the compound directly into
      a H-beta zeolite. Protonation of the aromatic ring, and thus the loss of
      symmetry, activated a vibrational ring mode at 1600 cm(-)(1). Furthermore, an
      electronic transition around 26 000 cm(-)(1), which was totally absent for the
      neutral species, was an obvious consequence of protonation. A parallel study of
      hexamethylbenzene adsorbed on a beta zeolite virtually free from protons did not
      show those distinctive spectral features. On the basis of the gas-phase proton
      affinity of hexamethylbenzene, a complete proton transfer from the zeolite
      framework to the molecule is, according to conventional considerations, not
      expected. The hexamethylbenzenium ion is stable in the zeolite cavities at least
      up to 200 degrees C. The remarkable persistence of this carbenium ion may be
      attributed to spatial constraints imposed by the tight fit of the cation inside
      the zeolite channels. Hexamethylbenzene is a relevant reaction intermediate in
      the methanol-to-hydrocarbons reaction and also plays a central role as a coke
      precursor in zeolite-catalyzed reactions that involve polymethylbenzenes.

PMID- 14677979
TI  - Thermal stereomutations and stereochemically elucidated [1,3]-carbon sigmatropic
      shifts of 1-(E)-propenyl-2-methylcyclobutanes giving 3,4-dimethylcyclohexenes.
AB  - The thermal stereomutations and [1,3] carbon sigmatropic shifts shown by (+)
      (1S,2S)-trans-1-(E)-propenyl-2-methylcyclobutane and by (-)-(1S,2R)-cis-1-(E)
      propenyl-2-methylcyclobutane in the gas phase at 275 degrees C leading to 3,4
      dimethylcyclohexenes have been followed. The reaction-time-dependent data for
      concentrations and enantiomeric excess values for substrates and [1,3] shift
      products have been deconvoluted to afford rate constants for the discrete
      isomerization processes. Both trans and cis substrates react through four
      stereochemically distinct [1,3] carbon shift paths. For one enantiomer of the
      trans reactant the relative rate constants are k(si) = 58%, k(ar) = 5%, k(sr) =
      33%, and k(ai) = 4%. For a single enantiomer of the cis reactant, k'(si) = 18%,
      k'(ar) = 11%, k'(sr) = 51%, and k'(ai) = 20%. A trans starting material reacts
      through orbital symmetry allowed suprafacial,inversion and antarafacial,retention
      paths to give trans-3,4-dimethylcyclohexenes 63% of the time. A cis isomer reacts
      to give the more stable trans-3,4-dimethylcyclohexenes through orbital symmetry
      forbidden suprafacial,retention and antarafacial,inversionpaths 71% of the time.
      The [1,3] carbon sigmatropic shifts are not controlled by orbital symmetry
      constraints. They seem more plausible rationalized as proceeding through
      diradical intermediates having some conformational flexibility after formation
      and before encountering an exit channel. The distribution of stereochemical
      outcomes may well be conditioned by dynamic effects. The thermal stereomutations
      of the 1-(E)-propenyl-2-methylcyclobutanes take place primarily through one
      center epimerizations. For the trans substrate, the relative importance of the
      three distinction rate constants are k(2) = 48%, k(1) = 34%, and k(12) = 18%. For
      the cis isomer, k'(2) = 44%, k'(1) = 32%, and k'(12) = 24%. These patterns are
      reminiscent of ones determined for stereomutations in 1,2-disubstitued
      cyclopropanes.

PMID- 14677980
TI  - Intramolecular hydroamination/cyclization of conjugated aminodienes catalyzed by
      organolanthanide complexes. Scope, diastereo- and enantioselectivity, and
      reaction mechanism.
AB  - Organolanthanide complexes of the general type Cp'(2)LnCH(TMS)(2) (Cp' = eta(5)
      Me(5)C(5); Ln = La, Sm, Y; TMS = SiMe(3)) and CGCSmN(TMS)(2) (CGC =
      Me(2)Si(eta(5)-Me(4)C(5))((t)()BuN)) serve as effective precatalysts for the
      rapid, regioselective, and highly diastereoselective intramolecular
      hydroamination/cyclization of primary and secondary amines tethered to conjugated
      dienes. The rates of aminodiene cyclizations are significantly more rapid than
      those of the corresponding aminoalkenes. This dienyl group rate enhancement as
      well as substituent group (R) effects on turnover frequencies is consistent with
      proposed transition state electronic demands. Kinetic and mechanistic data
      parallel monosubstituted aminoalkene hydroamination/cyclization, with turnover
      limiting C=C insertion into the Ln-N bond to presumably form an Ln-eta(3) allyl
      intermediate, followed by rapid protonolysis of the resulting Ln-C linkage. The
      rate law is first-order in [catalyst] and zero-order in [aminodiene]. However,
      depending on the particular substrate and catalyst combination, deviations from
      zero-order kinetic behavior reflect competitive product inhibition or self
      inhibition by substrate. Lanthanide ionic radius effects and ancillary ligation
      effects on turnover frequencies suggest a sterically more demanding Ln-N
      insertion step than in aminoalkene cyclohydroamination, while a substantially
      more negative DeltaS( double dagger ) implies a more highly organized transition
      state. Good to excellent diastereoselectivity is obtained in the synthesis of 2,5
      trans-disubstituted pyrrolidines (80% de) and 2,6-cis-disubstituted piperidines
      (99% de). Formation of 2-(prop-1-enyl)piperidine using the chiral C(1)-symmetric
      precatalyst (S)-Me(2)Si(OHF)(CpR)SmN(TMS)(2) (OHF = eta(5)-octahydrofluorenyl; Cp
      = eta(5)-C(5)H(3); R = (-)-menthyl) proceeds with up to 71% ee. The highly
      stereoselective feature of aminodiene cyclization is demonstrated by concise
      syntheses of naturally occurring alkaloids, (+/-)-pinidine and (+)-coniine from
      simple diene precursors.

PMID- 14677981
TI  - Lithium 2,2,6,6-tetramethylpiperidide-mediated alpha- and beta-lithiations of
      epoxides: solvent-dependent mechanisms.
AB  - Lithium 2,2,6,6-tetramethylpiperidide (LiTMP)-mediated alpha- and beta
      lithiations of epoxides are described. LiTMP displays a markedly higher
      reactivity than does lithium diisopropylamide, consistent with literature
      reports. Detailed rate studies of LiTMP/THF and LiTMP/Me(2)NEt mixtures reveal
      similar rates but significant mechanistic differences. LiTMP-mediated alpha
      lithiation of cis-cyclooctene oxide with subsequent oxacarbenoid formation and
      transannular C-H insertion proceeds via monosolvated dimers in both THF and
      Me(2)NEt. LiTMP-mediated beta-lithiation of 2,3-dimethyl-2-butene oxide affords
      the corresponding allylic alcohol via a monosolvated monomer in THF and a
      monosolvated dimer in Me(2)NEt. We discuss how the solvent-dependent aggregation
      of LiTMP markedly influences the rate profile. The reaction transition structures
      are examined with density functional computations.

PMID- 14677982
TI  - Isotope effects and the nature of selectivity in rhodium-catalyzed
      cyclopropanations.
AB  - The mechanism of the dirhodium tetracarboxylate catalyzed cyclopropanation of
      alkenes with both unsubstituted diazoacetates and vinyl- and phenyldiazoacetates
      was studied by a combination of (13)C kinetic isotope effects and density
      functional theory calculations. The cyclopropanation of styrene with methyl
      phenyldiazoacetate catalyzed by Rh(2)(octanoate)(4) exhibits a substantial (13)C
      isotope effect (1.024) at the terminal olefinic carbon and a smaller isotope
      effect (1.003-1.004) at the internal olefinic carbon. This is consistent with a
      highly asynchronous cyclopropanation process. Very similar isotope effects were
      observed in a bisrhodium tetrakis[(S)-N-(dodecylbenzenesulfonyl)prolinate]
      (Rh(2)(S-DOSP)(4) catalyzed reaction, suggesting that the chiral catalyst engages
      in a very similar cyclopropanation transition-state geometry. Cyclopropanation
      with ethyl diazoacetate was concluded to involve an earlier transition state,
      based on a smaller terminal olefinic isotope effect (1.012-1.015). Density
      functional theory calculations (B3LYP) predict a reaction pathway involving
      complexation of the diazoesters to rhodium, loss of N(2) to afford a rhodium
      carbenoid, and an asynchronous but concerted cyclopropanation transition state.
      The isotope effects predicted for reaction of a phenyl-substituted rhodium
      carbenoid with styrene match within the error of the experimental values,
      supporting the accuracy of the theoretical calculations and the rhodium carbenoid
      mechanism. The accuracy of the calculations is additionally supported by
      excellent predictions of reaction barriers, stereoselectivity, and reactivity
      trends. The nature of alkene selectivity and diastereoselectivity effects in
      these reactions is discussed, and a new model for enantioselectivity in Rh(2)(S
      DOSP)(4)-catalyzed cyclopropanations is presented.

PMID- 14677983
TI  - Y-shaped amphiphilic brushes with switchable micellar surface structures.
AB  - We observed novel nanoscale surface structures of segregated pinned micelles and
      craterlike micelles formed by grafted Y-shaped molecules and their reversible
      reorganization in selective solvents. The Y-shaped molecules have two
      incompatible polymer chains (polystyrene and poly(tert-butyl acrylate)) attached
      to a functional stemlike segment capable of covalent grafting to a functionalized
      silicon surface. Postgrafting hydrolysis of poly(tert-butyl acrylate) arms
      imparts amphiphilicity to the brush. We demonstrated that spatial constraints
      induced by a chemical junction of two relatively short (6-10 nm) dissimilar arms
      in such Y-shaped molecules lead to the formation of segregated micellar surface
      nanostructures in the grafted layer. We proposed a model of these segregated
      pinned micelles and the corresponding reverse micelles (craterlike structures)
      featuring different segregation states of hydrophobic polystyrene and hydrophilic
      poly(acrylic acid) arms. The arms undergo conformational rearrangements in
      selective solvents in a controlled and reversible fashion. These nanoscale
      structural reorganizations define adaptive macroscopic wetting surface properties
      of the amphiphilic Y-shaped brushes. This surface structure and switchable
      behavior can be considered as a promising way toward the patterning of solid
      substrates with adaptive nanowells, which could be used for trapping of adsorbing
      nanoscale objects.

PMID- 14677984
TI  - Structural characterization of crystalline ternary inclusion compounds at the air
      water interface.
AB  - Crystalline ternary inclusion monolayers consisting of a two-dimensional hydrogen
      bonded host network of guanidinium (G) ions and organosulfonate (S) amphiphiles,
      and biphenylalkane guests, can be generated at the air-water interface through
      synergistic structural enforcement by hydrogen bonding and host-guest packing.
      Surface pressure-area isotherms of the 4'-hexadecylbiphenyl-4-sulfonate (C16BPS)
      amphiphile in the presence of G, with or without guest, are characterized by lift
      off molecular areas expected for the GS sheet based on single-crystal X-ray
      structures of homologous bulk crystals. Intercalation of biphenylalkane guests (4
      C(n)()H(2)(n)()(+1)-C(6)H(4)-C(6)H(5), n = 1, 4, 6, 10, 16; denoted CnBP) between
      organosulfonate hydrophobes, which define pocketlike cavities in the GS monolayer
      host, afford ternary inclusion monolayers with a 1:1 host-guest stoichiometry.
      These inclusion monolayers are less compressible than the guest-free host,
      consistent with dense packing of the biphenylalkane moieties of the host and the
      biphenylalkane guests. The inclusion monolayers are distinguished from the
      amorphous guest-free host and from selected guanidinium-free mixed monolayers by
      structural characterization with grazing-angle incidence X-ray diffraction
      (GIXD). The GIXD data for the ternary (G)C16BPS:C16BP and (G)C16BPS:C6BP
      inclusion monolayers obtained upon compression are consistent with a rectangular
      unit cell. The dimensions of these unit cells and refinement of the GIXD data
      suggest a "rotated shifted ribbon" GS hydrogen-bonding motif similar to that
      observed in some bulk GS crystals, including (G)(ethylbiphenylsulfonate). GIXD
      reveals that (G)C16BPS:C16BP and (G)C16BPS:C6BP are more crystalline than the
      corresponding guanidinium-free mixed monolayers. The (G)C16BPS:C6BP inclusion
      monolayer is stable upon compression, even though the alkyl-alkyl host-guest
      interactions are reduced due to the shorter hexyl substituents of the guest,
      demonstrating an important reinforcing role for the hydrogen-bonded GS sheet. The
      structure of a C16BPS:tetracosane (C24) mixed monolayer is independent of G; the
      unit cell symmetry and dimensions suggest a structure governed by alkyl-alkane
      interactions that prohibit formation of a GS network. These results illustrate
      that the existence of ternary inclusion monolayers with an intact GS network
      requires guest molecules that are structurally homologous with the hydrophobes of
      the host, in this case biphenylalkanes. The observation of these inclusion
      compounds suggests an approach for introducing functional nonamphiphilic
      molecules to an air-water interface through inclusion in a well-defined host.

PMID- 14677985
TI  - Photoinitiated polymerization of columnar stacks of self-assembled trialkyl-1,3,5
      benzenetricarboxamide derivatives.
AB  - A disk-shaped molecule, N-(5-sorbyl-pentyl)-N',N"-di(n-octyl)benzene-1,3,5
      tricarboxamide (1), has been synthesized and assembled into a columnar stack in
      cyclohexane. Using a photoinitiated process, we polymerized monomer 1 in its self
      assembled state and analyzed the resulting poly-1. On cooling a boiling
      cyclohexane solution of 1, the molecules aggregate via amide hydrogen bonds, as
      supported by the position of the N-H stretching band in FT-IR spectroscopy.
      Evidence of helical columnar stacking of 1 in the aggregate is provided by an
      induced CD effect upon blending 1 with a chiral side-chain homologue 3 in a so
      called "sergeants and soldiers" experiment. The columnar assembly in cyclohexane
      was polymerized by UV light (365 nm) irradiation in the presence of 2,2-dimethoxy
      2-phenylacetophenone as radical photoinitiator. The polymerization occurs
      selectively to give 1,4-polymer with isolated trans C=C bonds, as shown by FT-IR,
      and (1)H and (13)C NMR spectroscopy. Lack of polymerization of methyl sorbate (4)
      under identical conditions, and low incorporation of 4 in copolymerizations with
      1 in cyclohexane, suggests that the polymerization preferentially occurs within
      the columnar assembly. Size exclusion chromatography shows that the degree of
      polymerization (X(n)()) based on number average molecular weight is approximately
      65. Incorporation of small amounts of nonpolymerizable derivatives 2 and 3 into
      the columns has no effect on X(n)() and conversion. Molecular models show that
      the polymerizable sidearm of 1 is long enough to span the distance between the
      monomers in the chiral stack. Under the atomic force microscope (AFM), purified
      samples of polymerized 1 displayed nanometer-sized fibrous morphologies with a
      high-axial-ratio (>150), uniform width (60 nm), and a thickness (1.0 nm) which
      corresponds to the width of the benzene tricarboxamide core of 1, whereas
      aggregates of nonpolymerized 1 yield a featureless image due to their
      instability.

PMID- 14677986
TI  - Transfer of pi-conjugated columnar stacks from solution to surfaces.
AB  - Three hydrogen-bonded oligo(p-phenylenevinylene)s, OPV3, OPV4, and OPV5, that
      differ in conjugation length have been synthesized and fully characterized. All
      three compounds contain chiral side chains, long aliphatic chains, and a ureido-s
      triazine hydrogen bonding unit. (1)H NMR and photophysical measurements show that
      the OPV oligomers grow hierarchically in an apolar solvent; initially, dimers are
      formed by hydrogen bonds that subsequently develop into stacks by pi-pi
      interactions of the phenylenevinylene backbone with induced helicity via the
      chiral side chains. SANS measurements show that rigid cylindrical objects are
      formed. Stacks of OPV4 have a persistence length of 150 nm and a diameter of 6
      nm. OPV3 shows rigid columnar domains of 60 nm with a diameter of 5 nm.
      Temperature and concentration variable measurements show that the stability of
      the stacks increases with the conjugation length as a result of more favorable pi
      pi interactions. The transfer of the single cylinders from solution to a solid
      support as isolated objects is only possible when specific concentrations and
      specific solid supports are used as investigated by AFM. At higher
      concentrations, an intertwined network is formed, while, at low concentration,
      ill-defined globular objects are observed. Only in the case of inert substrates
      (graphite and silicium oxide) single fibers are visible. In the case of the
      repulsive surfaces (mica and glass), clustering of the stacks occurs, while, at
      attractive surfaces (gold), the stacks are destroyed.

PMID- 14677987
TI  - Intervalence (charge-resonance) transitions in organic mixed-valence systems.
      Through-space versus through-bond electron transfer between bridged aromatic
      (redox) centers.
AB  - Intervalence absorption bands appearing in the diagnostic near-IR region are
      consistently observed in the electronic spectra of mixed-valence systems
      containing a pair of aromatic redox centers (Ar(*)(+)/Ar) that are connected by
      two basically different types of molecular bridges. The through-space pathway for
      intramolecular electron transfer is dictated by an o-xylylene bridge in the mixed
      valence cation radical 3(*)(+) with Ar = 2,5-dimethoxy-p-tolyl (T), in which
      conformational mobility allows the proximal syn disposition of planar T(*)(+)/T
      redox centers. Four independent experimental probes indicate the large through
      space electronic interaction between such cofacial Ar(*)(+)/Ar redox centers from
      the measurements of (a) sizable potential splitting in the cyclic voltammogram,
      (b) quinonoidal distortion of T(*)(+)/T centers by X-ray crystallography, (c)
      "doubling" of the ESR hyperfine splittings, and (d) a pronounced intervalence
      charge-resonance band. The through (br)-bond pathway for intramolecular electron
      transfer is enforced in the mixed-valence cation radical 2a(*)(+) by the p
      phenylene bridge which provides the structurally inflexible and linear connection
      between Ar(*)(+)/Ar redox centers. The direct comparison of intramolecular rates
      of electron transfer (k(ET)) between identical T(*)(+)/T centers in 3(*)(+) and
      2a(*)(+)( )()indicates that through-space and through-bond mechanisms are equally
      effective, despite widely different separations between their redox centers. The
      same picture obtains for 3(*)(+) and 2a(*)(+)( )()from theoretical computations
      of the first-order rate constants for intramolecular electron transfer from
      Marcus-Hush theory using the electronic coupling elements evaluated from the
      diagnostic intervalence (charge-transfer) transitions. Such a strong coherence
      between theory and experiment also applies to the mixed-valence cation radical
      7(*)(+), in which the aromatic redox S center is sterically encumbered by
      annulation.

PMID- 14677988
TI  - Hole transfer in a C-shaped molecule: conformational freedom versus solvent
      mediated coupling.
AB  - The electronic coupling matrix elements attending the charge separation reactions
      of a C-shaped molecule containing an excited pyrene as the electron acceptor and
      a dimethylaniline as the donor are determined in aromatic, ether, and ester
      solvents. Band shape analyses of the charge-transfer emission spectra (CT -->
      S(0)) provide values of the reaction free energy, the solvent reorganization
      energy, and the vibrational reorganization energy in each solvent. The free
      energy for charge separation in benzene and toluene solvents is independently
      determined from the excited state equilibrium established between the locally
      excited pyrene S(1) state and the charge-transfer state. Analyses of the charge
      separation kinetics using the spectroscopically determined reorganization
      energies and reaction free energies indicate that the electronic coupling is
      solvent independent, despite the presence of a cleft between the donor and
      acceptor. Hence, solvent molecules are not involved in the coupling pathway. The
      orientations of the donor and acceptor units, relative to the spacer, are not
      rigidly constrained, and their torsional motions decrease solvent access to the
      cleft. Generalized Mulliken-Hush calculations show that rotation of the pyrene
      group about the bond connecting it to the spacer greatly modulates the magnitude
      of through-space coupling between the S(1) and CT states. The relationship
      between the torsional dynamics and the electron-transfer dynamics is discussed.

PMID- 14677989
TI  - Application of isomorphous replacement in the structure determination of a cubic
      liquid crystal phase and location of counterions.
AB  - A second generation monodendron with dodecyl end-groups based on the AB(3)
      monomer 3,4,5-trihydroxy benzoate has previously been shown to form a
      thermotropic cubic phase with Pmthremacr;n symmetry (Balagurusamy et al., J. Am.
      Chem. Soc. 1997, 119, 1539). A structure consisting of spherical "micelles" was
      proposed originally, but an alternative choice of structure factor phases, giving
      a structure of interlocked squashed columns, could not be ruled out by
      diffraction data on the original material alone. We have therefore synthesized
      two selectively fluorinated equivalent compounds, the carboxylic acid and its Rb
      salt, to be able to apply a variant of the isomorphous replacement
      crystallographic technique. On the basis of the electron density maps of the new
      labeled compounds, reconstructed using small-angle X-ray diffraction intensities,
      the interlocking columns model is unequivocally rejected and the spheres model is
      upheld. Furthermore, the location of the metal cation in the center of the
      "micelles" is directly confirmed. Micellar diameter was shown to decrease on
      fluorination of the dodecyl chain ends, and increase significantly on
      introduction of Rb. This is interpreted in terms of changes in the number of
      wedge-shaped dendrons fitting into a spherical micelle due to their changing
      taper angle. It was found that the Rb-rich regions at the centers of six out of
      eight "micelles" in the unit cell are elongated in the direction of their closest
      packing. This adds support to the suggestion of a partial "column-like" character
      of stacked rows of such micelles, consistent with the position of the
      Pmthremacr;n phase next to the columnar phase in the phase sequence of most taper
      shape compounds. The results illustrate the potential of isomorphous replacement,
      used a great deal in protein crystallography, in structure investigation of
      liquid crystals and supramolecular soft matter.

PMID- 14677990
TI  - Surfactant-assisted elimination of a high energy facet as a means of controlling
      the shapes of TiO2 nanocrystals.
AB  - The surfactant-mediated shape evolution of titanium dioxide anatase nanocrystals
      in nonaqueous media was studied. The shape evolves from bullet and diamond
      structures to rods and branched rods. The modulation of surface energies of the
      different crystallographic faces through the use of a surface selective
      surfactant is the key parameter for the shape control.

PMID- 14677991
TI  - Low-spin ferriheme models of the cytochromes: correlation of molecular structure
      with EPR spectral type.
AB  - The preparation and characterization of the following bis-imidazole and bis
      pyridine complexes of octamethyltetraphenylporphyrinatoiron(III), Fe(III)OMTPP,
      octaethyltetraphenylporphyrinatoiron(III), Fe(III)OETPP, and tetra-beta,beta'
      tetramethylenetetraphenylporphyrinatoiron(III), Fe(III)TC(6)TPP, are reported:
      paral-[FeOMTPP(1-MeIm)(2)]Cl, perp-[FeOMTPP(1-MeIm)(2)]Cl, [FeOETPP(1
      MeIm)(2)]Cl, [FeTC(6)TPP(1-MeIm)(2)]Cl, [FeOMTPP(4-Me(2)NPy)(2)]Cl, and
      [FeOMTPP(2-MeHIm)(2)]Cl. Crystal structure analysis shows that paral-[FeOMTPP(1
      MeIm)(2)]Cl has its axial ligands in close to parallel orientation (the actual
      dihedral angle between the planes of the imidazole ligands is 19.5 degrees ),
      while perp-[FeOMTPP(1-MeIm)(2)]Cl has the axial imidazole ligand planes oriented
      at 90 degrees to each other and 29 degrees away from the closest N(P)-Fe-N(P)
      axis. [FeOETPP(1-MeIm)(2)]Cl has its axial ligands close to perpendicular
      orientation (the actual dihedral angle between the planes of the imidazole
      ligands is 73.1 degrees ). In all three cases the porphyrin core adopts
      relatively purely saddled geometry. The [FeTC(6)TPP(1-MeIm)(2)]Cl complex is the
      most planar and has the highest contribution of a ruffled component in the
      overall saddled structure compared to all other complexes in this study. The
      estimated numerical contribution of saddled and ruffled components is 0.68:0.32,
      respectively. Axial ligand planes are perpendicular to each other and 15.3
      degrees away from the closest N(P)-Fe-N(P) axis. The Fe-N(P) bond is the longest
      in the series of octaalkyltetraphenylporphyrinatoiron(III) complexes due to
      [FeTC(6)TPP(1-MeIm)(2)]Cl having the least distorted porphyrin core. In addition
      to these three complexes, two crystalline forms each of [FeOMTPP(4
      Me(2)NPy)(2)]Cl and [FeOMTPP(2-MeHIm)(2)]Cl were obtained. In all four of these
      cases the axial planes are in nearly perpendicular planes in spite of quite
      different geometries of the porphyrin cores (from purely saddled to saddled with
      30% ruffling). The EPR spectral type correlates with the geometry of the OMTPP,
      OETPP and TC(6)TPP complexes. For the paral-[FeOMTPP(1-MeIm)(2)]Cl, a rhombic
      signal with g(1) = 1.54, g(2) = 2.51, and g(3) = 2.71 is consistent with nearly
      parallel axial ligand orientation. For all other complexes of this study, "large
      g(max)" signals are observed (g(max) = 3.61 - 3.27), as are observed for nearly
      perpendicular ligand plane arrangement. On the basis of this and previous work,
      the change from "large g(max)" to normal rhombic EPR signal occurs between axial
      ligand plane dihedral angles of 70 degrees and 30 degrees.

PMID- 14677992
TI  - Probing photoelectrochemical processes in Au-CdS nanoparticle arrays by surface
      plasmon resonance: application for the detection of acetylcholine esterase
      inhibitors.
AB  - The photoelectrochemical charging of Au-nanoparticles (NP) in a Au
      nanoparticle/CdS-nanoparticle array assembled on a Au-coated glass surface is
      followed by means of surface plasmon resonance (SPR) spectroscopy upon continuous
      irradiation of the sample. The charging of the Au-NPs results in the enhanced
      coupling between the localized surface plasmon of the Au-NP and the surface
      plasmon of the bulk surface, leading to a shift in the plasmon angle. The
      charging effect of the Au-NPs is supported by concomitant electrochemical
      experiments in the dark. Analysis of the results indicates that ca. 4.2 electrons
      are associated with each Au-nanoparticle under steady-state irradiation. The
      photoelectrochemical charging effect of the Au-NPs in the Au-CdS NP array is
      employed to develop a SPR sensor for acetylcholine esterase inhibitors.

PMID- 14677993
TI  - Polymerization from the surface of single-walled carbon nanotubes - preparation
      and characterization of nanocomposites.
AB  - Single-walled carbon nanotubes were functionalized along their sidewalls with
      phenol groups using the 1,3-dipolar cycloaddition reaction. These phenols could
      be further derivatized with 2-bromoisobutyryl bromide, resulting in the
      attachment of atom transfer radical polymerization initiators to the sidewalls of
      the nanotubes. These initiators were found to be active in the polymerization of
      methyl methacrylate and tert-butyl acrylate from the surface of the nanotubes.
      However, the polymerizations were not controlled, leading to the production of
      high molecular weight polymers with relatively large polydispersities. The
      resulting polymerized nanotubes were analyzed by IR, Raman spectroscopy, DSC,
      TEM, and AFM. The nanotubes functionalized with poly(methyl methacrylate) were
      found to be insoluble, while those functionalized with poly(tert-butyl acrylate)
      were soluble in a variety of organic solvents. The tert-butyl groups of these
      appended polymers could also be removed to produce nanotubes functionalized with
      poly(acrylic acid), resulting in structures that are soluble in aqueous
      solutions.

PMID- 14677994
TI  - Systematic synthesis and characterization of single-crystal lanthanide
      orthophosphate nanowires.
AB  - A simple hydrothermal method has been developed for the systematic synthesis of
      lanthanide orthophosphate crystals with different crystalline phases and
      morphologies. It has been shown that pure LnPO(4) compounds change structure with
      decreasing Ln ionic radius: i.e., the orthophosphates from Ho to Lu as well as Y
      exist only in the tetragonal zircon (xenotime) structure, while the
      orthophosphates from La to Dy exist in the hexagonal structure under hydrothermal
      treatment. The obtained hexagonal structured lanthanide orthophosphate LnPO(4)
      (Ln = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, and Dy) products have a wirelike
      morphology. In contrast, tetragonal LnPO(4) (Ln = Ho, Er, Tm, Yb, Lu, Y) samples
      prepared under the same experimental conditions consist of nanoparticles. The
      obtained hexagonal LnPO(4) (Ln = La --> Tb) can convert to the monoclinic
      monazite structured products, and their morphologies remained the same after
      calcination at 900 degrees C in air (Hexagonal DyPO(4) is an exceptional case, it
      transformed to tetragonal DyPO(4) by calcination), while the tetragonal structure
      for (Ho--> Lu, Y)PO(4) remains unchanged by calcination. The resulting LnPO(4)
      (Ln = La --> Dy) products consist almost entirely of nanowires/nanorods with
      diameters of 5-120 nm and lengths ranging from several hundreds of nanometers to
      several micrometers. Europium doped LaPO(4) nanowires were also prepared, and
      their photoluminescent properties were reported. The optical absorption spectrum
      of CePO(4) nanowires was measured and showed some differences from that of bulk
      CePO(4) materials. The possible growth mechanism of lanthanide phosphate
      nanowires was explored in detail. X-ray diffraction, field-emission scanning
      electron microscopy, transmission electron microscopy, electron diffraction,
      infrared absorption spectra, X-ray photoelectron spectroscopy, optical absorption
      spectra, and photoluminescence spectra have been employed to characterize these
      materials.

PMID- 14677995
TI  - Structure of the first silicate molecular sieve with 18-ring pore openings, ECR
      34.
AB  - The three-dimensional microporosity of zeolite frameworks have allowed their
      widespread use in industry as heterogeneous catalysts, absorbents, and ion
      exchangers. While the phosphate analogues of zeolites having up to 24 tetrahedral
      atoms in the pore openings are known, silicate-based zeolites have, until now,
      been limited to 14-membered ring pore openings. We now disclose the structure and
      characterization of the synthetic zeolite ECR-34, which can be prepared from a
      mixed alkali metal reaction gel containing tetraethylammonium (TEA) cations. Its
      structure has been determined from powder diffraction data and shows ECR-34 to be
      hexagonal with the dimensions a, b = 21.030(1) A, c = 8.530(1) A, containing one
      dimensional, 18-ring pores with 10 A diameter free openings. ECR-34 is stable to
      800 degrees C and is able to absorb and ion-exchange large organic molecules. The
      existence of ECR-34 suggests the potential of preparing other thermally stable
      silicate molecular sieves with extra-large pores.

PMID- 14677996
TI  - M2(hpp)4Cl2 and M2(hpp)4, where M = Mo and W: preparations, structure and
      bonding, and comparisons with C2, C2H2, and C2Cl2 and the hypothetical molecules
      M2(hpp)4(H)2.
AB  - The reaction between M(2)Cl(2)(NMe(2))(4), where M = Mo or W, and Hhpp (8 equiv)
      in a solid-state melt reaction at 150 degrees C yields the compounds
      M(2)(hpp)(4)Cl(2) 1a (M = Mo) and 1b (M = W), respectively, by the elimination of
      HNMe(2) [hpp is the anion derived from deprotonation of 1,3,4,6,7,8-hexahydro-2H
      pyrimido[1,2-a]pyrimidine, Hhpp]. Purification of 1a and 1b is achieved by
      sublimation of the excess Hhpp and subsequent recrystallization from either
      CH(2)Cl(2) or CHCl(3) (or CDCl(3)). By single-crystal X-ray crystallography, the
      structures of 1a and 1b are shown to contain a central paddlewheel-like
      M(2)(hpp)(4) core with Mo-Mo = 2.1708(8) A (from CH(2)Cl(2)), 2.1574(5) A (from
      CDCl(3)), W-W = 2.2328(2) A (from CDCl(3)), and M-N = 2.09(1) (av) A. The Cl
      ligands are axially ligated (linear Cl-M-M-Cl) with abnormally long M-Cl bond
      distances that, in turn, depend on the presence or absence of hydrogen bonding to
      chloroform. The quadruply bonded compounds M(2)(hpp)(4), 2a (M = Mo), and 2b (M =
      W), can be prepared from the reactions between 1,2-M(2)R(2)(NMe(2))(4) compounds,
      where R = (i)()Bu or p-tolyl, and Hhpp (4 equiv) in benzene by ligand replacement
      and reductive elimination. The compounds 2a and 2b are readily oxidized, and in
      chloroform they react to form 1a and 1b, respectively. The electronic structure
      and bonding in the compounds 1a, 1b, 2a, and 2b have been investigated using
      gradient corrected density functional theory employing Gaussian 98. The bonding
      in the M-M quadruply bonded compounds, 2a and 2b, reveals M-M delta(2) HOMOs and
      extensive mixing of M-M pi and nitrogen ligand lone-pair orbitals in a manner
      qualitatively similar to that of the M(2)(formamidinates)(4). The calculations
      indicate that in the chloride compounds, 1a and 1b, the HOMO is strongly M-Cl
      sigma antibonding and weakly M-M sigma bonding in character. Formally there is a
      M-M triple bond of configuration pi(4)sigma(2), and the LUMO is the M-M delta
      orbital. An interesting mixing of M-M and M-Cl pi interactions occurs, and an
      enlightening analogy emerges between these d(4)-d(4) and d(3)-d(3) dinuclear
      compounds and the bonding in C(2), C(2)H(2), and C(2)Cl(2), which is interrogated
      herein by simple theoretical calculations together with the potential bonding in
      axially ligated compounds where strongly covalent M-X bonds are present. The
      latter were represented by the model compounds M(2)(hpp)(4)(H)(2). On the basis
      of calculations, we estimate the reactions M(2)(hpp)(4) + X(2) to give
      M(2)(hpp)(4)X(2) to be enthalpically favorable for X = Cl but not for X = H.
      These results are discussed in terms of the recent work of Cotton and Murillo and
      our attempts to prepare parallel-linked oligomers of the type [[bridge]-[M(2)]
      ](n)().

PMID- 14677997
TI  - Solventless synthesis of monodisperse Cu2S nanorods, nanodisks, and
      nanoplatelets.
AB  - Cu(2)S nanocrystals with disklike morphologies were synthesized by the
      solventless thermolysis of a copper alkylthiolate molecular precursor. The
      nanodisks ranged from circular to hexagonal prisms from 3 to 150 nm in diameter
      and 3 to 12 nm in thickness depending on the growth conditions. High resolution
      transmission electron microscopy (HRTEM) revealed the high chalcocite (hexagonal)
      crystal structure oriented with the c-axis ([001] direction) orthogonal to the
      favored growth direction. This disk morphology is thermodynamically favored as it
      allows the extension of the higher energy [100] and [110] surfaces with respect
      to the [001] planes. The hexagonal prism morphology also appears to relate to
      increased C-S bond cleavage of adsorbed dodecanethiol along the more energetic
      [100] facets relative to [001] facets. Monodisperse Cu(2)S nanodisks self
      assemble into ribbons of stacked platelets. This solventless approach provides a
      new technique to synthesize anisotropic metal chalcogenide nanostructures with
      shapes that depend on both the face-sensitive thermodynamic surface energy and
      the surface reactivity.

PMID- 14677998
TI  - Syntheses, characterizations, and coordination chemistry of the 10-vertex
      phosphadicarbaboranes 6-R-arachno-6,8,9-PC2B7H11 and 6-R-arachno-6,5,7-PC2B7H11.
AB  - The 10-vertex phosphadicarbaboranes, 6-R-arachno-6,8,9-PC(2)B(7)H(11) (1) (R = Ph
      1a or Me 1b) and 6-R-arachno-6,5,7-PC(2)B(7)H(11) (2) (R = Ph 2a or Me 2b) have
      been synthesized using in situ dehydrohalogenation reactions of RPCl(2) (R = Ph
      or Me) with the arachno-4,5-C(2)B(7)H(13) and arachno-4,6-C(2)B(7)H(13)
      carboranes, respectively. X-ray crystallographic determinations in conjunction
      with DFT/GIAO/NMR calculations and NMR spectroscopic studies have established
      that both 1 and 2 have open cage structures based on an icosahedron missing two
      vertexes. The two isomeric compounds differ in the positions of the carbons and
      bridging hydrogens on the open face. Studies of the reactions of 2a with
      BH(3).THF, S(8), and hydrogen peroxide demonstrated that 2a shows strong donor
      properties yielding the compounds endo-6-H(3)B-exo-6-Ph-arachno-6,5,7
      PC(2)B(7)H(11) (3), endo-6-S-exo-6-Ph-arachno-6,5,7-PC(2)B(7)H(11) (4), and endo
      6-O-exo-6-Ph-arachno-6,5,7-PC(2)B(7)H(11) (5) in which the BH(3), S, and O
      substitutents are bonded to an electron lone pair localized at the phosphorus
      endo-position. The reaction of 2a with an excess of S(8) results in the loss of a
      framework boron to produce the unique open-cage compound micro(7,8)-[HS(Ph)P]
      hypho-7,8-C(2)B(6)H(11) (6). 2a also formed the donor complexes cis-(eta(1)-[6-Ph
      arachno-6,5,7-PC(2)B(7)H(11)])(2)PtBr(2) (7) and trans-(eta(1)-[6-Ph-arachno
      6,5,7-PC(2)B(7)H(11)])(2)PdBr(2) (8) in which the metal fragment is bonded in an
      eta(1)-fashion at the phosphorus endo-position. In these complexes, 2a is
      functioning as a two-electron sigma donor to the metals and can thus be
      considered as an analogue of the PR(3) ligands in the classical cis
      (PPh(3))(2)PtBr(2) and trans-(PPh(3))(2)PdBr(2) coordination complexes. Although
      1a did not show the donor properties exhibited by 2a, its dianion 6-Ph-6,8,9
      PC(2)B(7)H(9)(2)(-) (1a(2)()(-)()) readily formed eta(4)-coordinated complexes
      with late transition metals including 8-Ph-7-(Ph(3)P)(2)-nido-7,8,10,11
      PtPC(2)B(7)H(9) (9), 7-Ph-11-(eta(5)-C(5)H(5))-nido-11,7,9,10-CoPC(2)B(7)H(9)
      (10), and commo-Ni-(7-Ni-8'-Ph-nido-8',10',11'-PC(2)B(7)H(9))(7-Ni-8-Ph-nido
      8,10,11-PC(2)B(7)H(9)) (11).

PMID- 14677999
TI  - Bonding self-assembled, compact organophosphonate monolayers to the native oxide
      surface of silicon.
AB  - A new method is described to prepare strongly bonded, compact monolayer films of
      alkyl- or arylphosphonates on the native oxide surface of Si (SiO(2)/Si). This
      method is illustrated for octadecyl- and alpha-quarterthiophene-2-phosphonates.
      For both cases, AFM shows comprehensive coverage of the SiO(2)/Si surface. The
      thickness of the continuous film of 4TP/SiO(2)/Si was measured both by AFM and by
      X-ray reflectivity to be ca. 18 A. Direct gravimetric analysis shows surface
      coverage by alpha-quarterthiophene-2-phosphonate to be about 0.66 nmol/cm(2),
      which corresponds to molecular packing in the film close to that of crystalline
      alpha-quarterthiophene. Coverage by octadecylphosphonate was ca. 0.90 nmol/cm(2),
      corresponding to a cross-sectional area of about 18.5 A(2)/molecule, consistent
      with close-packed alkyl chains.

PMID- 14678000
TI  - Polymorphic forms of a gold(I) arylacetylide complex with contrasting
      phosphorescent characteristics.
AB  - The spectroscopic properties and crystal structures of the gold(I) arylacetylide
      complexes [(R(3)P)Au(Ctbd1;CAr)] (R = Cy, Ar = 4-nitrophenyl, 1; 4
      trifluoromethylphenyl, 2; pentafluorophenyl, 3; R = Ph, Ar = 4-nitrophenyl, 4)
      have been examined. The dipole-allowed and -forbidden transitions of 1 (4 in
      parentheses) at lambda(max) 340 (336) and ca. 485 (470) nm in CH(2)Cl(2) solution
      at 298 K are assigned to the singlet and triplet intraligand charge transfer
      (ILCT) transitions of the 4-nitrophenylacetylide moiety, whereas 2 (3 in
      parentheses) shows localized singlet and triplet acetylenic pipi transitions at
      lambda(max) 287 (276) and 426 nm, respectively. Two polymorphs of 1 with
      contrasting phosphorescent characteristics have been identified. At 298 K, the
      emissive form of 1, as well as 2-4, are highly phosphorescent with peak maximum
      at 504, 425, 521, and 495 nm, respectively; the other polymorph of 1 is
      nonemissive at 298 K but emission is detected at 77 K with peak maximum at 486
      nm. Crystallographic studies reveal that the major differences between the
      emissive and nonemissive forms of 1 are the orientations of the molecular dipoles
      and the dihedral angles between neighboring 4-nitrophenyl moieties. Crystal 2 is
      isostructural to the nonemissive form of 1, but does not display polymorphism.
      The molecular planes of two neighboring lumophores are coplanar in the emissive
      form of 1, parallel in 4, and nearly perpendicular (78.6 degrees ) to each other
      in the nonemissive form of 1. Both the nature of the excited state and the
      dihedral angle between adjacent [Au(Ctbd1;CAr)] moieties determine the
      phosphorescent properties of these molecular crystals.

PMID- 14678001
TI  - Theoretical analysis of the electronic structure and bonding stability of the
      TCNE dimer dianion (TCNE) 2 2-.
AB  - The (TCNE)(2)(2)(-) dimer dianion formed by connecting two TCNE(-) anions via a
      four-center, two-electron pi-orbital bond is studied using ab initio theoretical
      methods and a model designed to simulate the stabilization due to surrounding
      counterions. (TCNE)(2)(2)(-) is examined as an isolated species and in a
      solvation environment representative of tetrahydrofuran (THF) solvent. The
      intrinsic strength of this novel bond and the influences of internal Coulomb
      repulsions, of solvent stabilization and screening, and of counterion
      stabilization are all considered. The geometry, electronic and thermodynamic
      stabilities, electronic absorption spectra, and electron detachment energies of
      this novel dianion are examined to help understand recent experimental findings.
      Our findings lead us to conclude that the (TCNE)(2)(2)(-) dianion's observation
      in solid materials is likely a result of its stabilization by surrounding
      countercations. Moreover, our results suggest the dianion is geometrically
      metastable in THF solution, with a barrier to dissociation into two TCNE(-)
      anions that can be quickly surmounted at room temperature but not at 77 K. This
      finding is consistent with what is observed in laboratory studies of low- and
      room-temperature solutions of salts containing this dianion. Finally, we assign
      two peaks observed (at 77 K in methyl-THF glass) in the UV-vis region to (1)
      electronic transitions involving the four-center orbitals and (2) detachment of
      an electron from the four-center pi-bonding orbital to generate (TCNE)(2)(-) + e(
      ).

PMID- 14678002
TI  - Assessment of cooperativity in self-assembly.
AB  - A method has been proposed to assess cooperativity in self-assembly processes.
      The method is based on a clear distinction between intermolecular and
      intramolecular processes which are compared with the corresponding reference
      reactions. It has been applied to two classical cases, namely the self-assembly
      of helicates and of porphyrin ladders, by using data previously published by the
      groups of Lehn and Anderson, respectively. Contrarily to the conclusions of the
      authors, pointing out self-assembly processes driven by positive cooperativity,
      the method here presented indicates in both cases the absence of cooperative
      effects. The methods previously used to assess cooperativity, in particular
      Scatchard plot and/or Hill plot, are criticized as being inappropriate for self
      assembly, because they are pertinent to a specific case only, namely the
      intermolecular binding of a monovalent ligand L to a multivalent receptor M, a
      case very different from self-assembly which involves both inter- and
      intramolecular interactions. The present method underscores the fact that
      positive cooperativity in artificial self-assembling systems is probably much
      more rare than it was previously thought.

PMID- 14678003
TI  - Pseudomultidimensional NMR by spin-state selective off-resonance decoupling.
AB  - An alternate technique for accurately monitoring the chemical shift in
      multidimensional NMR experiments using spin-state selective off-resonance
      decoupling is presented here. By applying off-resonance decoupling on spin S
      during acquisition of spin I, we scaled the scalar coupling J(I,S) between the
      spins, and the residual scalar coupling turns out to be a function of the
      chemical shift of spin S. Thus, the chemical shift information of spin S is
      indirectly retained, without an additional evolution period and the accompanying
      polarization transfer elements. The detection of the components of the doublet
      using spin-state selection enables an accurate measurement of the residual scalar
      coupling and a precise value for the chemical shift, concomitantly. The spin
      state selection further yields two subspectra comprising either one of the two
      components of the doublet and thereby avoiding the overlap problems that arise
      from off-resonance decoupling. In general, spin-state selective off-resonance
      decoupling can be incorporated into any pulse sequence. Here, the concept of spin
      state selective off-resonance decoupling is applied to 3D (13)C or (15)N-resolved
      [(1)H,(1)H]-NOESY experiments, adding the chemical shift of the heavy atom
      attached to the hydrogen ((13)C or (15)N nuclei) with high resolution resulting
      in a pseudo-4D. These pseudo-4D heavy-atom resolved [(1)H, (1)H]-NOESY
      experiments contain chemical shift information comparable to that of 4D (13)C or
      (15)N-resolved [(1)H,(1)H]-NOESY, but with an increase in chemical shift
      resolution by 1-2 orders of magnitude.

PMID- 14678004
TI  - Iridium-catalyzed borylation of benzene with diboron. Theoretical elucidation of
      catalytic cycle including unusual iridium(v) intermediate.
AB  - Iridium-catalyzed borylation of benzene with diboron was theoretically
      investigated with the DFT method, where an iridium(I) boryl complex, Ir(Beg)(NN)
      1, and an iridium(III) tris(boryl) complex, Ir(Beg)(3)(NN) 14, (eg
      (ethyleneglycolato) = -OCH(2)CH(2)O-, NN = HN=CHCH=NH (diim) or 2,2'-bipyridine
      (bpy)) were adopted as models of active species and B(2)(eg)(2) was adopted as a
      model of bis(pinacolato)diboron (pinacolato = -OCMe(2)CMe(2)O-). Oxidative
      addition of a benzene C-H sigma-bond to 1 takes place with an activation barrier
      (E(a)) of 11.2 kcal/mol, followed by reductive elimination of phenylborane, Ph
      Beg, from Ir(Beg)(H)(Ph)(diim) with an activation barrier of 15.6 kcal/mol.
      Though the oxidative addition and the reductive elimination occur with moderate
      activation barriers, B(2)(eg)(2) much more easily reacts with 1 to afford 14 than
      does benzene, of which the activation barrier is very small (2.9 kcal/mol).
      Oxidative addition of the benzene C-H sigma-bond to 14 occurs with a moderate
      activation barrier of 24.2 kcal/mol to afford an unusual seven-coordinate
      iridium(V) complex, Ir(H)(Ph)(Beg)(3)(bpy) 16. From this complex, phenylborane Ph
      Beg is produced through the reductive elimination with concomitant formation of
      IrH(Beg)(2)(bpy) 17, where the activation barrier is 4.9 kcal/mol. Complex 17
      further reacts with diboron to form Ir(H)(Beg)(4)(bpy) (E(a) = 8.0 kcal/mol),
      followed by the reductive elimination of borane H-Beg (E(a) = 2.6 kcal/mol) to
      regenerate Ir(Beg)(3)(bpy), when diboron exists in excess in the reaction
      solution. After consumption of diboron, IrH(Beg)(2)(bpy) reacts with borane, H
      Beg, to form Ir(H)(2)(Beg)(3) (E(a) = 21.3 kcal/mol) followed by the reductive
      elimination of H(2), to regenerate Ir(Beg)(3)(bpy) with concomitant formation of
      H(2). Formation of the iridium(III) tris(boryl) complex 14 from IrCl(diim) and
      diboron was also theoretically investigated; IrCl(diim) undergoes two steps of
      oxidative addition of diboron to afford a seven-coordinate iridium(V) complex,
      IrCl(Beg)(4)(NN), from which the reductive elimination of Cl-Beg takes place
      easily to afford 14. From these results, it should be clearly concluded that the
      iridium(III) tris(boryl) complex is an active species and an unusual iridium(V)
      species is involved as a key intermediate in the reaction. Detailed discussion is
      presented on the full catalytic cycle and the importance of a seven-coordinate
      iridium(V) intermediate.

PMID- 14678005
TI  - Antiparallel triple helices. Structural characteristics and stabilization by 8
      amino derivatives.
AB  - The structural, dynamical, and recognition properties of antiparallel DNA
      triplexes formed by the antiparallel d(G#G.C), d(A#A.T), and d(T#A.T) motifs (the
      pound sign and dot mean reverse-Hoogsteen and Watson-Crick hydrogen bonds,
      respectively) are studied by means of "state of the art" molecular dynamics
      simulations. Once the characteristics of the helix are defined, molecular
      dynamics and thermodynamic integration calculations are used to determine the
      expected stabilization of the antiparallel triplex caused by the introduction of
      8-aminopurines. Finally, oligonucleotides containing 8-aminopurine derivatives
      are synthesized and tested experimentally using several approaches in a variety
      of systems. A very large stabilization of the triplex is found experimentally, as
      predicted by simulations. These results open the possibility for the use of
      oligonucleotides carrying 8-aminopurines to bind single-stranded nucleic acids by
      formation of antiparallel triplexes.

PMID- 14678006
TI  - A CASSCF/MR-CI study toward the understanding of wavelength-dependent and
      geometrically memorized photodissociation of formic acid.
AB  - The S(0), T(1), and S(1) potential energy surfaces for the HCOOH dissociation and
      isomerization processes have been mapped with different ab initio methods. The
      wavelength-dependent mechanism for the HCOOH dissociation was elucidated through
      the computed potential energy surfaces and the surface crossing points. The HCOOH
      molecules in S(1) by excitation at 248 nm mainly decay to the ground state via
      the S(0) and S(1) vibronic interaction, followed by molecular eliminations in the
      ground state. The S(1) direct dissociation to HCO((2)A') + OH((2)Pi) is the
      dominant pathway upon photoexcitation at 240-210 nm. Meanwhile, there is a slight
      probability that the system relaxes to the ground state via the S(0) and S(1)
      vibronic interaction at these wavelengths. After irradiation of HCOOH at 193 nm,
      the S(1) direct dissociation into HCO((2)A') + OH((2)Pi) is energetically the
      most favorable pathway. In view of high IC efficiency at the S(0)/S(1) conical
      crossing, the S(1) --> S(0) internal conversion via the S(0)/S(1) point can occur
      with considerable efficiency. In addition, the S(1) isomerization probably plays
      a dominant role in the partially conformational memory of the HCOOH
      photodissociation, which has been discussed in detail.

PMID- 14678007
TI  - Probing chiral selective reactions using a revised Kataura plot for the
      interpretation of single-walled carbon nanotube spectroscopy.
AB  - Raman spectroscopy on surfactant-dispersed, aqueous suspensions of single-walled
      carbon nanotubes is used to verify the energies of interband transitions and
      validate the spectral assignments of semiconducting and metallic nanotubes
      determined by spectrofluorimetry for the former and Raman excitation profiles for
      the latter. The results are compiled into an experimentally based mapping of
      transition versus nanotube diameter to revise those previously employed using
      single-electron theoretical treatments. Because this mapping provides the
      transitions associated with a precise chiral wrapping of a particular nanotube,
      it allows the monitoring of reaction pathways that are selective to the nanotube
      chirality vector. This is demonstrated using a model electron-transfer reaction
      of 4-chlorobenzenediazonium shown to be selective for metallic over
      semiconducting carbon nanotubes via charge-transfer stabilization of complexes at
      the surfaces of the former.

PMID- 14678008
TI  - Reversal of diuretic-induced hepatic encephalopathy with infusion of albumin but
      not colloid.
AB  - In patients with cirrhosis, dehydration induced by diuretics is a common
      precipitant of hepatic encephalopathy (HE), which may respond to volume
      expansion. The mechanism of HE in this situation is not fully understood. The
      present study evaluates the effect of plasma volume expansion on the severity of
      HE, plasma and urinary ammonia in patients with diuretic-induced HE. Fifteen
      patients with alcoholic cirrhosis and diuretic-induced HE of Grade 2 or more were
      enrolled. In eight patients, 4.5% human albumin solution (HAS) was used for
      volume expansion and in seven patients colloid (Gelofusine) was used. Significant
      improvement of HE Grade was observed at 24 h and was sustained at 72 h ( P <0.05)
      only in the group treated with HAS. There were similar and statistically
      significant reductions in plasma ammonia concentration, plasma renin activity and
      angiotensin II and an increase in mean arterial pressure, renal plasma flow and
      urinary ammonia excretion in both groups. Plasma malondialdehyde was elevated in
      both groups, but was reduced significantly only in the group treated with HAS.
      The findings of the present study show that plasma volume expansion results in
      significant reduction in plasma ammonia concentration, possibly through an
      increase in urinary ammonia excretion. This reduction in ammonia concentration
      translates into an improvement in mental state only in those patients treated
      with HAS in whom concomitant reduction in oxidative stress was observed. These
      data support the notion that other factors, such as oxidative stress, act as
      adjuncts to ammonia in the pathogenesis of diuretic-induced HE and suggest a
      possible role for albumin infusion in its treatment.

PMID- 14678009
TI  - Effect of hyperglycaemia on glucose concentration of human nasal secretions.
AB  - Glucose is not detectable in airways secretions of normoglycaemic volunteers, but
      is present at 1-9 mmol x l(-1) in airways secretions from people with
      hyperglycaemia. These observations suggest the existence of a blood glucose
      threshold at which glucose appears in airways secretions, similar to that seen in
      renal and salivary epithelia. In the present study we determined the blood
      glucose threshold at which glucose appears in nasal secretions. Blood glucose
      concentrations were raised in healthy human volunteers by 20% dextrose
      intravenous infusion or 75 g oral glucose load. Nasal glucose concentrations were
      measured using modified glucose oxidase sticks as blood glucose concentrations
      were raised. Glucose appeared rapidly in nasal secretions once blood glucose was
      clamped at approx. 12 mmol x l(-1) ( n =6). On removal of the clamp, nasal
      glucose fell to baseline levels in parallel with blood glucose concentrations. An
      airway glucose threshold of 6.7-9.7 mmol x l(-1) was identified ( n =12). In six
      subjects with normal glucose tolerance, blood glucose concentrations rose above
      the airways threshold and nasal glucose became detectable following an oral
      glucose load. The presence of an airway glucose threshold suggests that active
      glucose transport by airway epithelial cells normally maintains low glucose
      concentrations in airways secretions. Blood glucose exceeds the airway threshold
      after a glucose load even in people with normal glucose tolerance, so it is
      likely that people with diabetes or hyperglycaemia spend a significant proportion
      of each day with glucose in their airways secretions.

PMID- 14678010
TI  - Relevance of NAC-2, an Na+-coupled citrate transporter, to life span, body size
      and fat content in Caenorhabditis elegans.
AB  - We have cloned and functionally characterized an Na+-coupled citrate transporter
      from Caenorhabditis elegans (ceNAC-2). This transporter shows significant
      sequence homology to Drosophila Indy and the mammalian Na+-coupled citrate
      transporter NaCT (now known as NaC2). When heterologously expressed in a
      mammalian cell line or in Xenopus oocytes, the cloned ceNAC-2 mediates the Na+
      coupled transport of various intermediates of the citric acid cycle. However, it
      transports the tricarboxylate citrate more efficiently than dicarboxylates such
      as succinate, a feature different from that of ceNAC-1 (formerly known as
      ceNaDC1) and ceNAC-3 (formerly known as ceNaDC2). The transport process is
      electrogenic, as evidenced from the substrate-induced inward currents in oocytes
      expressing the transporter under voltage-clamp conditions. Expression studies
      using a reporter-gene fusion method in transgenic C. elegans show that the gene
      is expressed in the intestinal tract, the organ responsible for not only the
      digestion and absorption of nutrients but also for the storage of energy in this
      organism. Functional knockdown of the transporter by RNAi (RNA interference) not
      only leads to a significant increase in life span, but also causes a significant
      decrease in body size and fat content. The substrates of ceNAC-2 play a critical
      role in metabolic energy production and in the biosynthesis of cholesterol and
      fatty acids. The present studies suggest that the knockdown of these metabolic
      functions by RNAi is linked to an extension of life span and a decrease in fat
      content and body size.

PMID- 14678011
TI  - Drastic reduction of sarcalumenin in Dp427 (dystrophin of 427 kDa)-deficient
      fibres indicates that abnormal calcium handling plays a key role in muscular
      dystrophy.
AB  - Although the primary abnormality in dystrophin is the underlying cause for mdx (X
      chromosome-linked muscular dystrophy), abnormal Ca2+ handling after sarcolemmal
      microrupturing appears to be the pathophysiological mechanism leading to muscle
      weakness. To develop novel pharmacological strategies for eliminating Ca2+
      dependent proteolysis, it is crucial to determine the fate of Ca2+-handling
      proteins in dystrophin-deficient fibres. In the present study, we show that a key
      luminal Ca2+-binding protein SAR (sarcalumenin) is affected in mdx skeletal
      muscle fibres. One- and two-dimensional immunoblot analyses revealed the relative
      expression of the 160 kDa SR (sarcoplasmic reticulum) protein to be approx. 70%
      lower in mdx fibres when compared with normal skeletal muscles. This drastic
      reduction in SAR was confirmed by immunofluorescence microscopy. Patchy internal
      labelling of SAR in dystrophic fibres suggests an abnormal formation of SAR
      domains. Differential co-immunoprecipitation experiments and chemical cross
      linking demonstrated a tight linkage between SAR and the SERCA1
      (sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase 1) isoform of the SR Ca2+-ATPase.
      However, the relative expression of the fast Ca2+ pump was not decreased in
      dystrophic membrane preparations. This implies that the reduction in SAR and
      calsequestrin-like proteins plays a central role in the previously reported
      impairment of Ca2+ buffering in the dystrophic SR [Culligan, Banville, Dowling
      and Ohlendieck (2002) J. Appl. Physiol. 92, 435-445]. Impaired Ca2+ shuttling
      between the Ca2+-uptake SERCA units and calsequestrin clusters via SAR, as well
      as an overall decreased luminal ion-binding capacity, might indirectly amplify
      the Ca2+-leak-channel-induced increase in cytosolic Ca2+ levels. This confirms
      the idea that abnormal Ca2+ cycling is involved in Ca2+-induced myonecrosis.
      Hence, manipulating disturbed Ca2+ handling might represent new modes of
      abolishing proteolytic degradation in muscular dystrophy.

PMID- 14678013
TI  - Inhibition of hydroxyapatite formation by osteopontin phosphopeptides.
AB  - Osteopontin (OPN) is an acidic phosphoglycoprotein that is believed to function
      in the prevention of soft tissue calcification. In vitro studies have shown that
      OPN can inhibit the formation of hydroxyapatite (HA) and other biologically
      relevant crystal phases, and that this inhibitory activity requires
      phosphorylation of the protein; however, it is not known which phosphorylated
      residues are involved. We have synthesized peptides corresponding to four
      phosphoserine-containing sequences in rat OPN: OPN7-17, containing phosphoserines
      10 and 11; OPN41-52, containing phosphoserines 46 and 47; OPN248-264, containing
      phosphoserines 250, 257 and 262; and OPN290-301, containing phosphoserines 295
      297. The abilities of these peptides to inhibit de novo HA formation were
      determined using a constant-composition autotitration assay. All four OPN
      phosphopeptides caused a dose-dependent increase in nucleation lag time, but did
      not significantly affect subsequent formation of the crystals. However, OPN41-52
      (inhibitory constant 73.5 min/microM) and OPN290-301 (72.2 min/microM) were
      approx. 4 times more potent inhibitors than OPN7-17 (19.7 min/microM) and OPN247
      264 (16.3 min/microM). 'Scrambling' the amino acid sequence of OPN290-301
      resulted in decreased potency (45.6 min/microM), whereas omission of the
      phosphate groups from this peptide caused a greater decrease (5.20 min/microM).
      These findings have identified phosphorylated sequences that are important for
      the ability of rat bone OPN to inhibit HA crystal formation, and suggest that
      negative-charge density is an important factor in this activity.

PMID- 14678012
TI  - A proteomic approach to identify early molecular targets of oxidative stress in
      human epithelial lens cells.
AB  - Oxidative stress is one of the most relevant contributors of cataractogenesis. To
      identify early protein targets of oxidative stress in lens cells, we used a
      differential proteomics approach to CD5A human epithelial lens cells treated with
      500 microM H2O2 for 30 min. This dose of H2O2 was assayed to induce efficiently a
      block of cellular proliferation and to activate the oxidative stress-early
      inducible transcription factor EGR-1 (early growth response gene product 1),
      previously reported as stimulated factor in a model of cataractogenesis
      [Nakajima, Nakajima, Fukiage, Azuma and Shearer (2002) Exp. Eye Res. 74, 231
      236]. We identified nine proteins, which sensitively reacted to H2O2 treatment by
      using two-dimensional gel electrophoresis and matrix-assisted laserdesorption
      ionization-time-of-flight-MS. In addition to cytoskeletal proteins (tubulin
      1alpha and vimentin) and enzymes (phosphoglycerate kinase 1, ATP synthase beta,
      enolase alpha, nucleophosmin and heat-shock cognate 54 kDa protein), which
      presented quantitative differences in expression profiles, peroxiredoxin and
      glyceraldehyde 3-phosphate dehydrogenase showed changes in pI as a result of
      overoxidation. Mass-mapping experiments demonstrated the specific modification of
      peroxiredoxin I active-site cysteine into cysteic acid, thus providing an
      explanation for the increase in negative charge measured for this protein. With
      respect to other global differential approaches based on gene expression
      analysis, our results allowed us to identify novel molecular targets of oxidative
      stress in lens cells. These results indicate that a combination of different
      approaches is required for a complete functional understanding of the biological
      events triggered by oxidative stress.

PMID- 14678015
TI  - The clinical relevance of cytokeratin phenotyping in needle biopsy of liver
      metastasis.
AB  - Although cytokeratin (CK) phenotyping of metastatic tumors is now routine in many
      laboratories, the clinical relevance of the procedure has seldom been addressed.
      We carried out a prospective clinical study of 134 consecutive cases of
      metastatic adenocarcinoma of the liver diagnosed by needle biopsies stained
      routinely for CK20 and CK7. The most probable localization of the primary tumor,
      deduced from this staining pattern, was stated in the original pathology report.
      The present study compared this assignment with the information available at the
      time of interpretation of the liver biopsy, to the results of the subsequent
      clinical investigation, and to the officially reported cause of death as outcome.
      As expected, the primary tumors were localized in the colon or in the rectum in
      85% (34/40) of the CK20+/CK7- metastases. The definite diagnosis remained
      metastatic colorectal carcinoma in 83% (15/18) of the cases with diagnosed
      colorectal cancer before the liver biopsy. In the cases without a known primary
      tumor when the liver biopsy was interpreted, primary colorectal localization was
      accurately predicted in 86% (19/22) of the patients. Compared to the outcome, 77%
      (36/47) of the CK20+/CK7+ metastases had the expected pancreaticobiliary primary
      localization in 83% (30/36) without any primary tumor being known at the time of
      interpretation of the liver biopsy. In contrast, the majority of CK20- metastatic
      carcinomas had an unexpected primary localization, 50% (16/32) in the CK20-/CK7+
      and 60% (9/15) in the CK20-/CK7- subgroup. In addition, the origin of the liver
      metastasis remained unknown in 37% (12/32) of CK20-/CK7+ cases. Thus, the
      CK20+/CK7- phenotype indicates a colorectal origin of the liver metastasis with
      considerable accuracy and independently of the available clinical information.
      The same is true for CK20+/CK7+ metastases, which indicate primary tumor
      localization in the pancreas or in the biliary tree. The results in the CK20-
      subgroups of the liver metastases are disappointing and cannot substantially help
      the clinical investigation.

PMID- 14678014
TI  - Peptide fragments of the dihydropyridine receptor can modulate cardiac ryanodine
      receptor channel activity and sarcoplasmic reticulum Ca2+ release.
AB  - We show that peptide fragments of the dihydropyridine receptor II-III loop alter
      cardiac RyR (ryanodine receptor) channel activity in a cytoplasmic Ca2+-dependent
      manner. The peptides were AC (Thr-793-Ala-812 of the cardiac dihydropyridine
      receptor), AS (Thr-671-Leu-690 of the skeletal dihydropyridine receptor), and a
      modified AS peptide [AS(D-R18)], with an extended helical structure. The peptides
      added to the cytoplasmic side of channels in lipid bilayers at > or = 10 nM
      activated channels when the cytoplasmic [Ca2+] was 100 nM, but either inhibited
      or did not affect channel activity when the cytoplasmic [Ca2+] was 10 or 100
      microM. Both activation and inhibition were independent of bilayer potential.
      Activation by AS, but not by AC or AS(D-R18), was reduced at peptide
      concentrations >1 mM in a voltage-dependent manner (at +40 mV). In control
      experiments, channels were not activated by the scrambled AS sequence (ASS) or
      skeletal II-III loop peptide (NB). Resting Ca2+ release from cardiac sarcoplasmic
      reticulum was not altered by peptide AC, but Ca2+-induced Ca2+ release was
      depressed. Resting and Ca2+-induced Ca2+ release were enhanced by both the native
      and modified AS peptides. NMR revealed (i) that the structure of peptide AS(D
      R18) is not influenced by [Ca2+] and (ii) that peptide AC adopts a helical
      structure, particularly in the region containing positively charged residues.
      This is the first report of specific functional interactions between
      dihydropyridine receptor A region peptides and cardiac RyR ion channels in lipid
      bilayers.

PMID- 14678016
TI  - Epstein-Barr virus-related lymph node lesion resembling autoimmune disease-like
      clinicopathological findings in elderly patients. Report of three cases.
AB  - Three cases of Epstein-Barr virus (EBV)-related lymphoproliferative disorders in
      elderly patients showing autoimmune disease-associated lymphadenopathy-like
      clinicopathological findings have been reported. Clinically, they were
      characterized by systemic lymphadenopathy, "B" symptoms, polyclonal
      hypergammaglobulinemia, elevated serum LDH and transient presence of various
      autoantibodies, and absence of atypical lymphocytosis in peripheral blood. One
      case was associated with idiopathic thrombocytopenic purpura. The clinical course
      was self-limiting. Histologically, they exhibited numerous lymphoid follicles
      with hyperplastic germinal centers and atypical interfollicular widening with
      prominent vascular proliferation. In the paracortical area, there was a mixed
      infiltrate comprising small to medium-sized lymphocytes and plasma cells, and
      variable numbers of eosinophils and T- and B-immunoblasts. In situ hybridization
      demonstrated a varying number of EBV-infected lymphocytes in the germinal center
      as well as in the interfollicular area. Polymerase chain reaction demonstrated
      that neither clonal rearrangement of T-cell receptor gamma-gene nor
      immunoglobulin heavy-chain rearrangement was detected in two of the cases
      examined. Although acute EBV infection rarely occurs in older adults, EBV related
      to reactive lymphoproliferative disorder should be added to the differential
      diagnosis of autoimmune disease-associated lymphadenopathy and node-based
      peripheral T-cell lymphoma in elderly patients.

PMID- 14678018
TI  - Elevated number of cells secreting transforming growth factor beta in Guillain
      Barre syndrome.
AB  - We used ELISPOT and cell ELISA to study secretion of IL-4, IFN-gamma, TGF-beta,
      IL-6, and TNF-alpha by circulating mononuclear cells during the course of
      Guillain-Barre syndrome (GBS). Compared to healthy controls, patients with GBS
      had higher numbers of TGF-beta-secreting cells and the number of individuals with
      myelin-peptide-induced IL-4 and TGF-beta secretion was higher in the GBS group.
      No significant differences were seen concerning the predominantly pro
      inflammatory cytokines IFN-gamma, IL-6 or TNF-alpha. Our findings indicate a down
      regulatory role for TGF-beta and IL-4 in GBS.

PMID- 14678017
TI  - Cancer of unknown primary: clinicopathologic correlations.
AB  - Cancer of unknown primary origin (CUP) accounts for 5-10% of all malignant tumors
      at presentation and remains the death certificate diagnosis in 0.5-5% of
      patients. We investigated CUP patients whose primary site remained unknown
      throughout the entire clinical course. We reviewed 9,436 consecutive autopsies
      performed between 1984 and 1999 at the Mayo Clinic, matched with 177,167 cancer
      patients treated in the same time period. Sixty-four patients who died of CUP
      underwent postmortem examination. Antemortem pathologic diagnoses were obtained
      in 57 patients, agreed with postmortem diagnoses in 98%, and included
      adenocarcinoma (n=44), undifferentiated carcinoma (n=7), squamous cell carcinoma
      (n=3), and others (n=3). Autopsy located the primary site in 35 patients (55%).
      Common primary sites were lung (n=8), the pancreaticobiliary (n=13) and GI tracts
      (n=9). Of 43 patients evaluated for tumor-specific therapy, only six received no
      further oncologic treatment and untreated patients survived a median of 57 (range
      10-280) days, compared with 225 (range 19-1,129) days for patients treated with
      chemotherapy and/or radiotherapy (n=37). Our findings show that (1) autopsy
      studies provide a valuable tool for quality control in the setting of CUP, and
      (2) treated patients have a small but significant survival benefit.

PMID- 14678019
TI  - Akt/PKB activation in gastric carcinomas correlates with clinicopathologic
      variables and prognosis.
AB  - Akt/protein kinase B (PKB) plays an important role in cell survival. However, the
      role of Akt in the biology of gastric cancer has not been well studied. We sought
      to investigate the expression of Akt or phosphorylated Akt (pAkt) in human
      gastric carcinomas and to analyze the relationship between Akt or pAkt and the
      clinicopathologic parameters. The expressions of Akt and pAkt were evaluated
      immunohistochemically in 311 gastric carcinomas using the tissue array method.
      Akt expression was detected in 74% of the tumors and pAkt expression in 78%. pAkt
      was highly expressed in the early stage of pTNM (p=0.011). We also found an
      inverse association between pAkt and lymphatic invasion (p=0.01) or lymph node
      metastasis (p=0.008). pAkt expression was significantly correlated with a higher
      survival in patients with stage I carcinomas (p=0.0003). Interestingly, combined
      evaluation revealed that the group with pAkt-positive and lymph node-negative
      carcinomas showed a better prognosis than the other groups (p<0.0001). In
      addition, pAkt was shown to correlate positively with APC (p=0.002) and Smad4
      (p<0.0001) expression. These findings suggest that pAkt expression may help to
      predict the clinical outcome of gastric cancer patients.

PMID- 14678020
TI  - Increased sensitivity of Mycobacterium tuberculosis Cobas Amplicor PCR following
      brief incubation of tissue samples on Lowenstein-Jensen substrate.
AB  - The sensitivity of Mycobacterium tuberculosis Cobas Amplicor PCR (MTB-PCR) is
      considerably lower for tissue than for airway samples, depending on both lower
      bacterial content and presence of inhibitory substances in tissues. The aim of
      this study was to improve the sensitivity of MTB-PCR in inhibiting biopsy
      samples. A brief-culture method was applied to 33 inhibitory tissue samples out
      of 356 obtained in Laboratory I, and compared with 44/197 such samples treated by
      dilution in Laboratory II. We found that 2-3 days' incubation on Lowenstein
      Jensen substrate (LJ) significantly increased the sensitivity of MTB-PCR in
      samples exerting PCR inhibition. Sensitivity was 63% before and 92% following
      brief-culture of inhibitory tissue samples in Lab I, compared to 46% and 50%,
      respectively, with dilution in Lab II. Thus, dilution did not significantly
      increase sensitivity in inhibiting samples. Specificities were 99.4/99.4 and
      99.2/98.2, respectively. The higher sensitivity attained by the LJ-method was
      probably due to diffusion of inhibiting substances into the substrate, as well as
      to increase in numbers of bacteria after the brief-culture. This method adds
      substantially to the value of MTB-PCR of biopsy material.

PMID- 14678021
TI  - The endocrine pancreas in non-diabetic rats after short-term and long-term
      treatment with the long-acting GLP-1 derivative NN2211.
AB  - Glucagon-like peptide 1 (GLP-1) and GLP-1 receptor agonists increase the beta
      cell mass in rodent models of type 2 diabetes and enhance the proliferation rate
      of beta cells in vitro, while the long-term effect in vivo in non-diabetic
      animals is unknown. We studied the endocrine pancreas in non-diabetic Sprague
      Dawley rats after short- and long-term treatment with NN2211, an acetylated long
      acting derivative of GLP-1. Four groups of rats (n=6 for each group) received two
      daily injections with either NN2211 or vehicle for 1 or 6 weeks. NN2211-treated
      rats displayed a 10% lower body weight after both 1 week (p<0.001) and 6 weeks
      (p<0.005) of treatment. The mean beta-cell mass in NN2211-treated rats was
      increased by 19% after 1 week of treatment (p<0.05), but normalized after 6 weeks
      of treatment. No difference in alpha-cell mass, volume-weighted mean islet
      volume, or pancreas mass was found after 1 or 6 weeks of treatment. We conclude
      that NN2211 treatment of non-diabetic rats induces a sustained lower body weight,
      and an only temporary increase in the beta-cell mass, while the alpha-cell mass
      and the volume-weighted mean islet volume are unaffected by the treatment.

PMID- 14678022
TI  - Altered immunoglobulin isotype profile and anti-immature worm surface
      immunoglobulins in mice harboring a praziquantel-resistant Schistosoma mansoni
      isolate.
AB  - After placement in mice of PZQ-sensitive and -insensitive S. mansoni isolates
      obtained from villagers responding and not responding to PZQ, parasitological
      criteria reflecting their biological development and also the host anti-immature
      worm immunoglobulin isotypes were examined 8 and 10 weeks post infection. Hepatic
      granuloma diameter, hepatic histopathological changes and immunolocalization of
      IgG and IgM on the surface of PZQ-sensitive and -resistant worms were also
      examined 10 weeks post infection. Data showed that parasitological criteria were
      not significantly different between mice infected with the PZQ-sensitive and 
      insensitive S. mansoni isolates. As regards serum immunoglobulins, in mice
      infected with the PZQ-insensitive S. mansoni isolate, IgG and IgG1 were
      significantly (p<0.05) lower 8 and 10 weeks post infection, respectively (1.41+/
      0.07 and 1.08+/-0.10 and 1.35+/-0.06 and 1.09+/-0.07) than in mice infected with
      the PZQ-sensitive S. mansoni isolate (1.73+/-0.15 and 1.38+/-0.10 and 1.73+/-0.17
      and 1.54+0.21) after the same observation periods. IgM level was nearly the same
      while IgE was lower than that recorded in mice infected with the PZQ-sensitive S.
      mansoni isolate. IgG immunofluorescence was also lower (60%+/-6.78) on the
      surface of resistant worms than that of sensitive worms (66.6%+/-5.27);
      meanwhile, hepatic granuloma diameter was significantly larger (296.5+/-3.0 vs
      283.6+/-4.0) in mice infected with the PZQ-insensitive S. mansoni isolate with
      higher percentage of intact eggs. Differences in the immunogenic make up of PZQ
      sensitive and -insensitive S. mansoni isolates qualitatively and/or
      quantitatively favoring a certain Th cell subpopulation response could be the
      underlying reason for such differences recorded in the host immunoglobulin
      isotype response and also the egg-induced hepatic histopathological changes.

PMID- 14678023
TI  - Granulocytic sarcoma presenting with lymph node infarction at disease onset.
AB  - A completely infarcted lymph node is an unusual event. However, lymph node
      infarction should alert the pathologist to the considerable likelihood of
      malignant lymphoma. We report two unusual cases of acute myeloid leukemia
      presenting with granulocytic sarcoma at disease onset with a lymph node lesion
      exhibiting extensive lymph node infarction. The infarcted tissue contained
      numerous eosinophilic cell ghosts. There were some islands of degenerated,
      pyknotic medium-sized nuclei resembling lymphoblasts present in the necrotic
      area. By immunohistochemistry, these medium sized cells were CD3-, CD20-, CD34+,
      CD43+, CD45RO-, CD68-, CD79a- and myeloperoxidase+ in both cases. Differentiation
      of granulocytic sarcoma from malignant lymphomas is important for adequate
      therapy. The present cases indicate that granulocytic sarcoma should be added to
      the list of differential diagnoses for lymph node infarction.

PMID- 14678024
TI  - High expression of nitric oxide synthases is a favorable prognostic sign in non
      small cell lung carcinoma.
AB  - Immunohistochemical expression of neuronal (n), endothelial (e), and inducible
      (i) NOS and their association with the type, grade, apoptotic index,
      proliferation of tumors and the survival of patients were investigated in 89
      biopsies of non-small cell lung carcinoma (NSCLC). In tumor cells, expression of
      iNOS was detected in 35/89 (40%) cases, while 79/89 (89%) and 72/89 (81%) cases
      showed weak to intense positivity for eNOS and nNOS, respectively. Strong eNOS
      staining was seen significantly more often in adenocarcinomas than in squamous
      cells carcinomas (p=0.016), and iNOS immunoreactivity was seen more often in
      grade I-II tumors than in grade III tumors (p=0.024). There was no significant
      difference between the low and high apoptotic indexes or between the low and high
      proliferation rates of tumors in any instance of NOS staining. The patients with
      tumors showing high nNOS expression tended to have better survival than the
      others (p=0.06, log-rank; p=0.04, Bresow; p=0.048, Tarone-Ware). Similarly, the
      patients with tumors showing high expression of iNOS, eNOS and nNOS, as
      determined by a combined sum index, had a better survival than those with a low
      sum index for these enzymes (p<0.05). The results show intense expression of eNOS
      and nNOS, and moderate expression of iNOS in tumor cells of non-small cell
      carcinoma. Intense NOSs expression seems to be a favorable prognostic sign in non
      small cell lung carcinoma.

PMID- 14678025
TI  - Zinc ions in beta-cells of obese, insulin-resistant, and type 2 diabetic rats
      traced by autometallography.
AB  - Zinc ions in the secretory granules of beta-cells are known to glue insulin
      molecules, creating osmotically stable hexamers. When the secretory granules open
      to the surface, the zinc ion pressure decreases rapidly and pH levels change from
      acid to physiological, which results in free insulin monomers and zinc ions. The
      released zinc ions have been suggested to be involved in a paracrine regulation
      of alpha- and beta-cells. Since zinc is intimately involved in insulin metabolism
      and because zinc homeostasis is known to be disturbed in type 2 diabetes, we
      decided to study the ultrastructural localisation of zinc ions in insulin
      resistant and type 2 diabetic rats as compared to controls. By means of
      autometallography, the only method available for demonstrating zinc ions at
      ultrastructural levels, we found zinc ions in the secretory granules and adjacent
      to the plasma membrane. The membrane-related staining outside the plasma membrane
      reflects release of zinc ions during exocytosis. No apparent difference was found
      in the ultrastructural localisation of zinc ions when we compared the obese
      Zucker (fa/fa) rats, representing the insulin resistance syndrome, and the GK
      rats, representing type 2 diabetes, with controls. This suggests that the
      ultrastructural localisation of zinc ions is unaffected by the development of
      type 2 diabetes in rats in a steady state of glycaemia.

PMID- 14678026
TI  - Cold ischemic injury of transplanted organs: some new strategies against an old
      problem.

PMID- 14678027
TI  - Whither living donors?

PMID- 14678028
TI  - An interview with Jean Dausset.

PMID- 14678029
TI  - New B7 family members with positive and negative costimulatory function.
AB  - The B7 family of T-cell costimulatory molecules has expanded considerably in
      recent years. Among the new costimulatory molecules discovered are inhibitory and
      activating pathways. Both ligands and receptors often have multiple binding
      partners, adding to the complexity of T-cell regulation. Some B7 molecules also
      exhibit reverse signaling, affecting activation of both antigen-presenting cells
      and T cells. An increased understanding of these pathways of T-cell regulation
      results in promising new therapeutics because T-cell interference can be better
      targeted to specific states of activation or location. This will decrease side
      effects such as systemic immunosuppression and increase efficiency. Targeting B7
      molecular pathways for either inhibiting or increasing cell-mediated immunity has
      so far shown promising results in models of autoimmunity, transplant rejection
      and tumor immunotherapy.

PMID- 14678030
TI  - Organ donors with malignant gliomas: an update.
AB  - The escalating shortage of organs motivates frequent reconsideration of concepts
      that guide the decision to accept or decline organs from donors with central
      nervous system (CNS) malignancy. Currently, a minority of patients who die
      annually of CNS malignancies are organ donors. Specifically, the organs of less
      than 0.5% of the 13 000 patients dying from glioma are procured and transplanted
      every year in the United States. This review seeks to clarify the risk of cancer
      transmission from transplantation of organs from donors with glioma. After
      considering historical precedence, we will systematically outline the clinical
      features of a potential organ donor with glioma that might reflect upon the risk
      of cancer transmission. We will then present recent knowledge regarding basic
      glioma biology that speaks to their metastatic potential and suggest rational
      strategies for the post-transplant management of recipients of organs from donors
      with glioma.

PMID- 14678031
TI  - Prevention of cold-preservation injury of cultured endothelial cells by
      catecholamines and related compounds.
AB  - The present study was conducted to dissect the underlying mechanisms by which
      catecholamines protect cells against preservation injury. To this end, we firstly
      defined the cellular and molecular differences between protected and nonprotected
      cells and secondly defined the mediators that were involved in cold-induced
      damage. Cold storage of untreated human umbilical vein endothelial cells (HUVECs)
      resulted in profound cellular damage as assessed by lactate dehydrogenase (LDH)
      release and by morphological changes, e.g. cell size alterations and loss of
      cytoskeletal organization. Treatment of HUVECs with catecholamines before cold
      storage prevented cellular damage in a dose- and time-dependent fashion. Similar
      results were obtained with carvedilol or its hydroxylated derivative BM91.0228.
      Protection was not receptor-mediated and did not require de novo protein
      synthesis. The onset of protection occurred relatively quickly and the duration
      was long lasting. Addition of superoxide dismutase (SOD) to untreated HUVECs
      during cold preservation also was protective. Oxidation of catecholamines
      completely abrogated the protective effect of these compounds on cold-induced
      damage. Both at 4 degrees and 37 degrees C, catecholamines reduced the amount of
      reactive oxygen species (ROS) produced by HUVECs. In conclusion we have
      demonstrated that catecholamines protect cells against preservation injury either
      by scavenging of ROS or by inhibition of ROS production.

PMID- 14678032
TI  - Earlier low-dose TBI or DST overcomes CD8+ T-cell-mediated alloresistance to
      allogeneic marrow in recipients of anti-CD40L.
AB  - Treatment with a single injection of anti-CD40L (CD154) monoclonal antibody (mAb)
      and fully mismatched allogeneic bone marrow transplant (BMT) allows rapid
      tolerization of CD4+ T cells to the donor. The addition of in vivo CD8 T-cell
      depletion leads to permanent mixed hematopoietic chimerism and tolerance. We now
      describe two approaches that obviate the requirement for CD8 T-cell depletion by
      rapidly tolerizing recipient CD8 T cells in addition to CD4 cells. Administration
      of donor-specific transfusion (DST) to mice receiving 3 Gy total body irradiation
      (TBI), BMT and anti-CD40L mAb on day 0 uniformly led to permanent mixed chimerism
      and tolerance, compared with only 40% of mice receiving similar treatment without
      DST. In the absence of DST, moving the timing of 3 Gy TBI to day -1 or day -2
      instead of day 0 led to rapid (by 2 weeks) induction of CD8+ cell tolerance, and
      also permitted uniform achievement of permanent mixed chimerism and donor
      specific tolerance in recipients of anti-CD40L and BMT on day 0. These nontoxic
      regimens overcome CD8+ and CD4+ T-cell-mediated alloresistance without requiring
      host T-cell depletion, permitting the induction of permanent mixed chimerism and
      tolerance.

PMID- 14678033
TI  - Matrix metalloproteinase inhibition decreases ischemia-reperfusion injury after
      lung transplantation.
AB  - Increased microvascular permeability and extravasation of inflammatory cells are
      key events of lung ischemia-reperfusion (IR) injury. The purpose of this study
      was to investigate the role of matrix metalloproteinases (MMP) in IR-induced
      alveolar capillary membrane disruption after experimental lung transplantation.
      We used a rat model of lung orthotopic transplantation (n = 86) with a prolonged
      cold ischemic phase. MMP2 and MMP9 were elevated 4 h after the onset of ischemia
      and further increased during reperfusion. Compared to sham values, the alveolar
      capillary membrane permeability increased by 105% and 82.6% after 4 h of ischemia
      and 2 h or 24 h of reperfusion, respectively. A 4- and 5-fold increase of the
      infiltration of ischemic tissue by neutrophils was also observed after 2 h and 24
      h of reperfusion. The PO2/FIO2 ratio dropped significantly from 244 to 76.6 after
      2 h of reperfusion and from 296.4 to 127.6 after 24 h of reperfusion. A
      nonselective inhibitor of MMP, administered to the rats and added to the
      preservation solution, reduced significantly the alveolar-capillary leakage, the
      transmigration of neutrophils and improved gas exchanges in animals submitted to
      4 h of ischemia combined with 2 h or 24 h of reperfusion. We conclude that
      inhibition of MMP attenuates IR injury after experimental lung transplantation.

PMID- 14678034
TI  - The novel JAK-3 inhibitor CP-690550 is a potent immunosuppressive agent in
      various murine models.
AB  - JAK-3 has been shown to play a key role in cytokine signaling via gammac, e.g. IL
      2, 4, 7, 9, 15, 21. The current study describes the immunosuppressive effects of
      CP-690550, a novel, small molecule inhibitor of JAK-3, in various murine models.
      In vitro, CP-690550 effectively inhibited a murine mixed lymphocyte reaction
      (MLR) (IC50= 91 nm). Mice chronically dosed with CP-690550 (1.5-15 mg/kg/day)
      demonstrated dose- and time-dependent alterations in lymphocyte subsets when
      examined by flow cytometry. The most dramatic change observed was a 96% reduction
      in splenic NK1.1 + TCRbeta- cell numbers following 21 days of treatment. Delayed
      type hypersensitivity (DTH) responses in sensitized mice were reduced in a dose
      dependent manner following treatment with the JAK-3 inhibitor (1.87-30 mg/kg,
      s.c.). Extended survival of neonatal Balb/c hearts implanted into the ear pinna
      of MHC mismatched C3H/HEN mice was observed with CP-690550 monotherapy (10-30
      mg/kg/day), but improved upon combination with cyclosporin (10 mg/kg/day). These
      data support the participation of JAK-3 in various lymphocyte homeostatic
      functions in mature mice. Furthermore, the ability of CP-690550 to extend cardiac
      allograft survival in murine models suggests it may afford a new treatment for
      prevention of transplant rejection.

PMID- 14678035
TI  - Bcl-XL expression in stem cells facilitates engraftment and reduces the need for
      host conditioning during bone marrow transplantation.
AB  - The prolonged survival of donor hematopoietic stem cells is crucial to the
      success of bone marrow transplantation. The anti-apoptotic gene Bcl-xL has been
      shown to promote survival of cells of the erythroid, myeloid and lymphoid
      lineages. To evaluate a potential therapeutic role for Bcl-xL, we used a
      retroviral vector to express Bcl-xL in donor cells used for murine bone marrow
      transplantation. We find that Bcl-xL expression in bone marrow cells facilitates
      hematopoietic reconstitution (as assessed by total cellularity) without altering
      cell differentiation. Most importantly, cells reconstituted with Bcl-xL are able
      to achieve high levels of donor chimerism even in non-ablative conditioning
      protocols in a syngeneic model of transplantation. Thus, expression of Bcl-xL by
      donor cells during bone marrow transplantation may provide a means to minimize
      host conditioning and toxicity while still achieving therapeutic degrees of mixed
      chimerism.

PMID- 14678036
TI  - CD4+ CD25+ CD62+ T-regulatory cell subset has optimal suppressive and
      proliferative potential.
AB  - CD4+ CD25+ regulatory T cells (Treg) are potent suppressors, and play important
      roles in autoimmunity and transplantation. Recent reports suggest that CD4+ CD25+
      Treg are not a homogeneous cell population, but the differences in phenotype,
      function, and mechanisms among different subsets are unknown. Here, we
      demonstrate CD4+ CD25+ Treg cells can be divided into subsets according to cell
      surface expression of CD62L. While both subsets express foxp3 and are anergic,
      the CD62L+ population is more potent on a per cell basis, and proliferates and
      maintains suppressive function far better than the CD62L- population and
      unseparated CD4+ CD25+ Treg. The CD62L+ population preferentially migrates to
      CCL19, MCP-1 and FTY720. Both CD62L+ and CD62L- subsets prevent the development
      of autoimmune gastritis and colitis induced by CD4+ CD25-CD45RBhigh cells in
      severe combined immunodeficiency (SCID) mice. Overall, these results suggest CD4+
      CD25+ Treg are not a homogenous cell population, but can be divided into at least
      two subsets according to CD62L expression. The CD62L+ subset is a more potent
      suppressor than the CD62L- population or unfractionated CD4+ CD25+ Treg cells,
      can be expanded far more easily in culture, and is more responsive to chemokine
      driven migration to secondary lymphoid organs. These properties may have
      significant implications for the clinical manipulation of the CD4+ CD25+ CD62L+
      cells.

PMID- 14678037
TI  - Composite "thymoheart" transplantation improves cardiac allograft survival.
AB  - We have generated a novel composite organ, the thymoheart, which facilitates the
      contemporaneous transfer of fully vascularized and functional donor thymic tissue
      to the host at the time of cardiac transplantation. Composite thymoheart
      allografts were prepared in MHC-inbred miniature swine by implanting autologous
      thymic tissue into donor hearts 60-90 days before organ procurement. Thymoheart
      allografts and unmanipulated control hearts were then transplanted into three
      groups, each treated with the same 12 days of cyclosporine. MHC-matched
      thymohearts transplanted into euthymic recipients had a minimum survival ranging
      between 72 and 194 days vs. 42-64 days for unmanipulated control hearts (p =
      0.02). MHC class I-disparate thymohearts transplanted into euthymic recipients
      had a minimum survival ranging between 64 and 191 days vs. 30-55 days for
      unmanipulated control hearts (p = 0.01). MHC class I-disparate thymohearts
      transplanted into thymectomized recipients survived between 41 and 70 days vs. 8
      27 days for unmanipulated control hearts (p = 0.01). Cellular and humoral
      functional assays, and skin grafting, confirmed the presence of donor-specific
      hyporesponsiveness in long-term thymoheart allografts recipients. The transfer of
      vascularized, functional donor thymic tissue to the host at the time of cardiac
      transplantation may provide a novel approach to the induction of tolerance in
      human heart transplant recipients.

PMID- 14678038
TI  - Immunosuppression and the risk of post-transplant malignancy among cadaveric
      first kidney transplant recipients.
AB  - The success of renal transplantation may be counterbalanced by serious adverse
      medical events. The effect of immunosuppression on the incidence of de novo
      neoplasms among kidney recipients should be monitored continuously. Using data
      from the Scientific Registry of Transplant Recipients, we studied the association
      of induction therapy by immunosuppression with antilymphocyte antibodies, with
      the development of de novo neoplasms. The study population included more than 41
      000 recipients who received a cadaveric first kidney transplant after December
      31, 1995, and were followed through February 28, 2002. Using Cox regression
      models, we estimated time to development of two types of malignancy: de novo
      solid tumors and post-transplant lymphoproliferative disorder (PTLD). We made
      adjustments for several patient demographic factors and comorbidities. Induction
      therapy was significantly associated with a higher relative risk (RR) of PTLD (RR
      = 1.78, p < 0.001), but not with a greater likelihood of de novo tumors (RR =
      1.07, p = 0.42). Treatment with maintenance tacrolimus vs. cyclosporine showed a
      significantly different RR of developing de novo tumors for recipients with
      induction than for those not receiving induction (p = 0.024). These new estimates
      of the magnitude of malignancy risk associated with induction therapy may be
      useful for clinical practice.

PMID- 14678039
TI  - Prevalence and outcomes of multiple-listing for cadaveric kidney and liver
      transplantation.
AB  - Transplant candidates are permitted to register on multiple waiting lists. We
      examined multiple-listing practices and outcomes, using data on 81 481 kidney and
      26 260 liver candidates registered between 7/1/95 and 6/30/00. Regression models
      identified factors associated with multiple-listing and its effect on relative
      rates of transplantation, waiting list mortality, kidney graft failure, and liver
      transplant mortality. Overall, 5.8% (kidney) and 3.3% (liver) of candidates
      multiple-listed. Non-white race, older age, non-private insurance, and lower
      educational level were associated with significantly lower odds of multiple
      listing. While multiple-listed, transplantation rates were significantly higher
      for nearly all kidney and liver candidate subgroups (relative rate [RR]= 1.42
      2.29 and 1.82-7.41, respectively). Waiting list mortality rates were
      significantly lower while multiple-listed for 11 kidney subgroups (RR = 0.22
      0.72) but significantly higher for 7 liver subgroups (RR = 1.44-5.93), suggesting
      multiple-listing by healthier kidney candidates and sicker liver candidates.
      Graft failure was 10% less likely among multiple-listed kidney recipients.
      Multiple- and single-listed liver recipients had similar post-transplant
      mortality rates. Although specific factors characterize those transplant
      candidates likely to multiple-list, transplant access is significantly enhanced
      for almost all multiple-listed kidney and liver candidates.

PMID- 14678040
TI  - Histologic findings of antibody-mediated rejection in ABO blood-group
      incompatible living-donor kidney transplantation.
AB  - The purpose of this study was to characterize the histology of antibody-mediated
      rejection (AMR) in ABO blood-group-incompatible (ABOI) kidney transplants as well
      as on protocol biopsies performed at the time of stable allograft function.
      Between 5/99 and 1/02, we performed 32 ABOI kidney transplants (13 A2, 19 non-A2
      blood-group living donors). Nineteen biopsies were performed for allograft
      dysfunction, and 127 protocol biopsies were performed 0, 3, 7, 14, 28 days and 3
      and 12 months post transplant. Twenty-five of 32 patients have functioning
      allografts (mean 585 days post transplant). Nine of 32 (28%) developed clinical
      AMR. Biopsy revealed glomerular thrombi (78%), mesangiolysis (78%), peritubular
      capillary C4d staining (56%) and neutrophil infiltration (67%), interstitial
      hemorrhage and necrosis (56%) and arteriolar thrombi (33%). Subclinical AMR was
      diagnosed by protocol biopsies in four patients. Findings consisted of glomerular
      thrombi (100%), mesangiolysis (25%), and C4d staining (100%). In late protocol
      biopsies performed 214-420 days post transplant, mild mesangiolysis was seen in
      2/17 (11.7%), and C4d immunostaining was detected in 3/12 (25%). AMR is
      characterized by glomerular thrombi, mesangiolysis, peritubular capillary
      neutrophil infiltration interstitial hemorrhage, necrosis, and C4d deposition.
      Glomerular thrombi appear early in AMR and may appear prior to graft dysfunction.

PMID- 14678041
TI  - Herpes zoster infection following solid organ transplantation: incidence, risk
      factors and outcomes in the current immunosuppressive era.
AB  - Herpes zoster (HZ) infection is a frequent and serious complication of organ
      transplantation that has not been examined in the current era of
      immunosuppression. All solid organ transplants performed between 1994 and 1999 (n
      = 869) at our center were analyzed to determine the incidence, complications and
      risk factors for developing HZ. The overall incidence of HZ was 8.6% (liver 5.7%,
      renal 7.4%, lung 15.1% and heart 16.8%). The median time of onset was 9.0 months.
      We observed high rates of cutaneous scarring (18.7%) and post-herpetic neuralgia
      (42.7%). Independent organ-specific risk factors included: female gender and
      mycophenolate mofetil therapy (liver), and antiviral treatment other than
      prolonged cytomegalovirus (CMV) prophylaxis (renal and heart). For all organs
      combined, induction therapy and antiviral treatment other than prolonged CMV
      prophylaxis were independent predictors for the development of HZ. Herpes zoster
      is common and results in significant morbidity for solid organ transplant
      recipients. Risk factors include induction therapy and antiviral drug therapy
      other than CMV prophylaxis. The latter variable identifies a subpopulation that
      is likely at increased risk of latent herpesvirus reactivation. The high first
      year post-transplant incidence rate suggests immunization pretransplant, even in
      varicella zoster virus immunoglobulin seropositive individuals, may be
      preventative.

PMID- 14678042
TI  - EBV kidney allograft infection: possible relationship with a peri-graft
      localization of PTLD.
AB  - Post-transplant lymphoproliferative disorder (PTLD) is a grave complication of
      transplantation and the result of uncontrolled proliferation of B lymphocytes
      infected with Epstein-Barr virus (EBV). Herein we assess whether EBV infects
      renal grafts and whether there is a relationship between EBV kidney infection and
      PTLD. Allograft biopsies from 23 patients with PTLD were studied for the presence
      of EBV DNA and RNA (EBER-1, -2) by in situ hybridization and for CD21 by
      immunohistochemistry. Results were compared to 43 transplants from people without
      PTLD. EBV DNA and RNA were detected in 11/43 patients without PTLD (26%), and in
      15/23 (65%) patients with PTLD (p = 0.004). EBV DNA and RNA localized to proximal
      tubular cells and these cells showed up-regulation of the EBV receptor CD21. EBV
      infected allografts were noted in 12/12 patients with PTLD located near the
      allograft and in 3/11 (27%) of patients with PTLD distant from the graft.
      Multiple biopsies in eight patients showed that graft EBV infection can precede
      the diagnosis of PTLD by as long as 42 months. It is concluded that EBV can
      infect kidney allografts, and there appears to be a relationship between this
      infection and the presence of PTLD near the graft.

PMID- 14678043
TI  - Peritubular capillary changes and C4d deposits are associated with transplant
      glomerulopathy but not IgA nephropathy.
AB  - We examined our renal transplant population for glomerular diseases demonstrated
      on biopsy between January 1993 and April 2002, focusing on transplant
      glomerulopathy (TGP). Of 1156 patients followed in our clinics during this
      period, glomerular disease was diagnosed in 132 cases (11.4%). Glomerulonephritis
      was diagnosed in 86 transplants (7.4%), with IgA nephropathy (IgAN) being the
      commonest diagnosis [32 cases (2.8%)]. Thirty-one cases (2.7%) of biopsy-proven
      TGP were analyzed for associated factors compared with 27 cases (2.3%) of
      recurrent IgAN. Transplant glomerulopathy was less frequent with mycophenolate
      mofetil (MMF) and/or tacrolimus, whereas recurrent IgAN showed no such tendency
      (P= 0.02). Peritubular capillary (PTC) C4d deposition was observed in six of 24
      cases (25%) with TGP but none with recurrent IgAN (P= 0.02). Peritubular
      capillary basement membrane (BM) multilayering was significantly greater in TGP
      (4.92 +/- 2.94) than in recurrent IgAN (1.86 +/- 1.04) (P < 0.001). The graft
      survival of TGP was worse than recurrent IgAN (P= 0.05). The association of TGP
      with BM multilayering and C4d deposits in PTC suggests a generalized disorder of
      the graft microcirculation and its BM, owing to antibody-mediated rejection in at
      least some cases. Transplant glomerulopathy has a serious prognosis but is less
      frequent in patients on newer immunosuppression, unlike recurrent IgAN.

PMID- 14678044
TI  - Testosterone concentrations and sirolimus in male renal transplant patients.
AB  - Sirolimus damages the testes in animals; however, human data are sparse. We
      conducted a case-control study to obtain further insight into this issue and
      compared testosterone, follicle-stimulating hormone (FSH), luteinizing hormone
      (LH), and prolactin concentrations in matched renal transplant patients who did
      or did not receive sirolimus. We found that testosterone values were lower (11.2
      +/- 6.3 nmol/L vs. 15.5 +/- 7.7 nmol/L, p < 0.05), in 28 sirolimus-treated
      patients, compared to 28 non-sirolimus-treated controls. Furthermore, these
      patients more commonly had testosterone concentrations that were below our
      reference value for normal men. In contrast, FSH and LH concentrations were
      higher while prolactin levels were not different. These data are consistent with
      sirolimus-related testosterone suppression and suggest a need for further
      studies.

PMID- 14678045
TI  - Acute post-bacterial glomerulonephritis in renal transplant patients: description
      of three cases and review of the literature.
AB  - Only a few cases of acute post-infectious glomerulonephritis have been described
      in renal transplant patients. We report here three cases of acute post-bacterial
      glomerulonephritis in renal transplants. In contrast to the classic cases of post
      streptococcal glomerulonephritis the type of infection was heterogeneous:
      respectively, Escherichia coli bacteremia, a skin abscess, and cholangitis. The
      clinical presentation was characterized by a deterioration of graft function in
      two of our three patients. Acute renal dysfunction recovered in both patients,
      but in the long term the outcome was severe; two of the three patients lost their
      graft function. It is difficult to ascertain whether progression was due to
      chronic allograft nephropathy, to glomerulonephritis, or both. It may be
      concluded that acute post-infectious glomerulonephritis is a possible, although
      rare, complication in renal transplant recipients. It has an unusual presentation
      and may have a poor outcome in the long term. The role of therapy, if any, is
      still undefined.

PMID- 14678046
TI  - Sirolimus-induced pneumonitis: three cases and a review of the literature.
AB  - Interstitial pneumonitis is a rare disease that is seen in the context of some
      infections (e.g. PCP and CMV pneumonia), as side-effects of drugs (e.g. beta
      blockers, amiodarone) and rarely in the context of renal transplantation. It
      manifests itself usually as a pneumonic illness; with symptoms of dyspnea, cough,
      fatigue and sometimes fever. Characteristic radiological changes are bilateral
      lower zone haziness. Interstitial pneumonitis is now emerging in solid organ
      transplant patients secondary to sirolimus). We describe three cases of sirolimus
      induced pneumonitis in two patients who started sirolimus to permit cyclosporin
      withdrawal and in one patient initially started on sirolimus. The presentations
      in these cases ranged from insidious to fulminant; there was a rapid response to
      sirolimus withdrawal. This is an important syndrome, with an unknown frequency.

PMID- 14678048
TI  - Successful non-heart-beating donor organ retrieval in a patient with a left
      ventricular assist device.
AB  - Non-heart-beating donors (NHBD) represent an option to expand the organ supply
      with good results. We report a donor patient with a left ventricular assist
      device (LVAD) due to dilated cardiomyopathy in which controlled NHBD was
      performed. Due to the LVAD, a modified procurement technique was utilized. The
      liver and kidneys were procured and successfully transplanted. Patients and
      grafts are alive and well. Successful organ retrieval can be achieved on selected
      cases of NHBD with LVADs in which modifications of the procurement technique are
      implemented without jeopardizing the procurement and not increasing preservation
      injury.

PMID- 14678047
TI  - Successful simultaneous pancreas kidney transplantation from living-related donor
      against positive cross-match.
AB  - A positive pretransplant flow cytometry cross-match (FC-XM) allows precise
      identification of high-risk recipients vulnerable to hyperacute or accelerated
      rejection after transplantation. Living donor kidney transplant recipient
      candidates with positive cross-match have been successfully treated with a
      combination of plasmapheresis (therapeutic plasma exchange, TPEX) and intravenous
      immunoglobulin (IVIG), achieving conversion to negative cross-match and
      successful transplant. We report the first successful case of simultaneous
      pancreas kidney transplant (SPKT) from a living donor (LD) performed against an
      initially positive FC-XM, converted to negative using a protocol based on TPEX
      and IVIG in combination with antiCD20 monoclonal antibody. This strategy of
      overcoming the cross-match barriers in living donation may offer a chance of
      successful transplantation to highly sensitized candidates for SPKT, for whom
      cadaveric transplant is difficult to achieve.

PMID- 14678049
TI  - Decreased incidence of cytomegalovirus infection in thymoglobulin-treated
      transplant patients with 6 months of valganciclovir prophylaxis.

PMID- 14678051
TI  - Gender, gender role and brief alcohol interventions.

PMID- 14678052
TI  - Is marijuana use becoming a 'gateway' to nicotine dependence?

PMID- 14678054
TI  - Conversation with Michael A. H. Russell.

PMID- 14678055
TI  - Does disulfiram have a role in alcoholism treatment today?

PMID- 14678056
TI  - Disulfiram: cautions on liver function; how to supervise.

PMID- 14678057
TI  - Does disulfiram have a role in alcoholism treatment today? Not to forget about
      disulfiram's psychological effects.

PMID- 14678058
TI  - The disulfiram-ethanol reaction (DER) experience.

PMID- 14678060
TI  - Shape of the relapse curve and long-term abstinence among untreated smokers.
AB  - OBJECTIVE: To describe the relapse curve and rate of long-term prolonged
      abstinence among smokers who try to quit without treatment. METHOD: Systematic
      literature review. DATA SOURCES: Cochrane Reviews, Dissertation Abstracts,
      Excerpt Medica, Medline, Psych Abstracts and US Center for Disease Control
      databases plus bibliographies of articles and requests of scientists. STUDY
      SELECTION: Prospective studies of self-quitters or studies that included a no
      treatment control group. DATA EXTRACTION: Two reviewers independently extracted
      data in a non-blind manner. DATA SYNTHESIS: The number of studies was too small
      and the data too heterogeneous for meta-analysis or other statistical techniques.
      RESULTS: There is a paucity of studies reporting relapse curves of self-quitters.
      The existing eight relapse curves from two studies of self-quitters and five no
      treatment control groups indicate most relapse occurs in the first 8 days. These
      relapse curves were heterogeneous even when the final outcome was made similar.
      In terms of prolonged abstinence rates, a prior summary of 10 self-quitting
      studies, two other studies of self-quitters and three no-treatment control groups
      indicate 3-5% of self-quitters achieve prolonged abstinence for 6-12 month after
      a given quit attempt. CONCLUSIONS: More reports of relapse curves of self
      quitters are needed. Smoking cessation interventions should focus on the first
      week of abstinence. Interventions that produce abstinence rates of 5-10% may be
      effective. Cessation studies should report relapse curves.

PMID- 14678061
TI  - The efficacy of single-session motivational interviewing in reducing drug
      consumption and perceptions of drug-related risk and harm among young people:
      results from a multi-site cluster randomized trial.
AB  - AIM: To test whether a single session of motivational interviewing (discussing
      alcohol, tobacco and illicit drug use) would lead successfully to reduction in
      use of these drugs or in perceptions of drug-related risk and harm among young
      people. DESIGN: Cluster randomized trial, allocating 200 young people in the
      natural groups in which they were recruited to either motivational interviewing
      (n=105) or non-intervention education-as-usual control condition (n=95). SETTING:
      Ten further education colleges across inner London. PARTICIPANTS: Two hundred
      young people (age range 16-20 years) currently using illegal drugs, with whom
      contact was established through peers trained for the project. INTERVENTION: The
      intervention was adapted from the literature on motivational interviewing in the
      form of a 1-hour single-session face-to-face interview structured by a series of
      topics. MEASUREMENTS: Changes in self-reported cigarette, alcohol, cannabis and
      other drug use and in a range of drug-specific perceptions and other indicators
      of risk and harm. Measurement at recruitment and follow-up interview 3 months
      later. FINDINGS: A good follow-up rate (89.5%; 179 of 200) was achieved. In
      comparison to the control group, those randomized to motivational interviewing
      reduced their of use of cigarettes, alcohol and cannabis, mainly through
      moderation of ongoing drug use rather than cessation. Effect sizes were 0.37
      (0.15-0.6), 0.34 (0.09-0.59) and 0.75 (0.45-1.0) for reductions in the use of
      cigarettes, alcohol and cannabis, respectively. For both alcohol and cannabis,
      the effect was greater among heavier users of these drugs and among heavier
      cigarette smokers. The reduced cannabis use effect was also greater among youth
      usually considered vulnerable or high-risk according to other criteria. Change
      was also evident in various indicators of risk and harm, but not as widely as the
      changes in drug consumption. CONCLUSIONS: This study provides the first
      substantial evidence of non-treatment benefit to be derived among young people
      involved in illegal drug use in receipt of motivational interviewing. The
      targeting of multiple drug use in a generic fashion among young people has also
      been supported.

PMID- 14678062
TI  - Mortality in a cohort of opiate and amphetamine users in Perth, Western
      Australia.
AB  - AIMS: This study compares the hazard of death among opiate and amphetamine using
      clients who accessed drug treatment with individuals who had no specialist
      treatment contact between 1985 and 1998. DESIGN, SETTING, PARTICIPANTS: This was
      a retrospective cohort study of 4280 drug-using individuals (2887 opiate users,
      1393 amphetamine users) admitted to Perth metropolitan hospitals or Perth
      psychiatric institutions between 1985 and 1998. Of these, 1469 attended Next Step
      Specialist Drug and Alcohol Services (928 received methadone and 541 attended
      counselling or support groups) and 2811 had no contact with this service.
      METHODS: Data from two drug treatment programmes were linked with hospital
      morbidity, psychiatric services and the mortality database using record linkage.
      FINDINGS: The results show that people who were currently in drug treatment had a
      lower hazard of death compared with non-clients and those who had ceased
      treatment. Those who had ceased treatment more than 6 months ago had 7.0 times
      the hazard of all-cause death and 8.4 times the hazard of drug-cause death.
      Opiate users were at 1.4 times the hazard of all-cause death and 2.4 times the
      hazard of drug-cause death compared with amphetamine users. Males were at 1.79
      times the hazard of all-cause death and, unexpectedly, were found to be at 2.69
      times the hazard of drug-cause death compared with females. CONCLUSIONS:
      Treatment protected clients from premature death compared with people who did not
      receive treatment and also those who ceased treatment. While amphetamine users
      had a lower risk of mortality compared with opiate users, the full extent of the
      relationship between amphetamine use and mortality needs to be examined further.

PMID- 14678063
TI  - Exploration of adverse psychological symptoms in Yemeni khat users by the
      Symptoms Checklist-90 (SCL-90).
AB  - AIM: The present study was aimed at assessing associations between psychological
      symptoms and khat use in the Yemeni population. SETTING: The survey was performed
      in 2000/2001, in different zones including three urban and three rural areas.
      PARTICIPANTS: The survey was carried out in 800 Yemeni adults (15-76), both male
      and female, representing mainly urban populations of students, state employees
      and housewives. DESIGN: A cross-sectional survey was undertaken using face-to
      face interviews and no preset selection criteria regarding profession, socio
      economic status, age or gender. MEASUREMENT: The Symptoms Checklist-90 (SCL-90)
      was used containing 90 items, which cover nine scales of the following domains:
      somatization, depression, anxiety, phobia, hostility, interpersonal sensitivity,
      obsessive-compulsive, hostility, interpersonal sensitivity, paranoia and
      psychoticism. Details of khat use and socio-demographic data were also collected.
      FINDINGS: At least one life-time episode of khat use was reported in 81.6% of men
      and 43.3% of women. Male users tended to use more frequently. The incidence of
      adverse psychological symptoms was not greater in khat users; in fact, there was
      a negative association between the incidence of phobic symptoms and khat use.
      CONCLUSIONS: Khat use is very common in the Yemeni population, particularly men,
      but it is not associated with adverse psychological symptoms.

PMID- 14678064
TI  - Factors associated with Ecstasy use in Turkish students.
AB  - AIMS: The purpose of this study was to establish the factors associated with
      Ecstasy use in secondary school students in Turkey. DESIGN, SETTING AND
      PARTICIPANTS: This is a survey of a representative sample drawn from cities in
      different geographical regions in Turkey in 1998 and 2001. The questionnaire was
      administered to a total of 18,556 and 11,911 10th-grade students in 1998 and
      2001, respectively. MEASUREMENTS: The questionnaire administered in the study was
      adapted from the questionnaires used in 'Monitoring the Future' study in the
      United States and ESPAD (the European School Survey Project on Alcohol and Other
      Drugs). It included questions about demographic characteristics, family
      characteristics, school life, social contacts and use of substances. FINDINGS:
      While the percentage of those who used Ecstasy at least once in their life-times
      was 2.65% in 1998, the figure reached 3.31% in 2001. Male gender, older age, use
      of alcohol, cannabis, heroin and cocaine, non-medical use of psychotherapeutic
      drugs and participation in a meeting concerning the adverse effects of substance
      use were found to be significant variables predicting 'ever use' of Ecstasy in
      both years by logistic regression analysis. CONCLUSIONS: Ecstasy use, while low
      in Turkey, appears to be on the increase and follows a pattern in terms of
      correlates that is similar to other illicit drugs. Whatever the causes behind the
      rise in Ecstasy use, creative, personalized and informative educational
      programmes should be conducted in all educational institutions to curb Ecstasy
      use.

PMID- 14678065
TI  - 'You can't go without a fag...you need it for your hash'--a qualitative
      exploration of smoking, cannabis and young people.
AB  - AIMS: To examine the relationship between smoking tobacco and cannabis use among
      smokers in their mid-to-late teens. DESIGN AND PARTICIPANTS: Two qualitative
      studies in Scotland. One study used semistructured paired interviews involving 99
      16-19-year-old smokers, the other comprised eight focus groups involving 46 15-16
      year-old smokers. MEASUREMENT: The interviews and focus groups explored the role
      and meaning of smoking in the participants' lives, smoking histories and future
      cessation intentions and how these related to other aspects of their lives,
      particularly cannabis use. FINDINGS: Cannabis use was regarded as an important
      and enjoyable aspect of many of the participants' lives. Importantly, cannabis
      use and cigarette smoking were linked inextricably. Several reported how smoking
      joints had been a 'gateway' to smoking cigarettes. While most wanted to quit
      smoking cigarettes, cannabis use reinforced their cigarette smoking and few
      wanted to stop using cannabis. CONCLUSION: National studies need to be conducted
      to examine how widespread the problem identified is and tobacco control
      initiatives and smoking cessation treatment services need to consider urgently
      how to overcome the barrier that a desire on the part of young people to continue
      cannabis smoking poses to achieving a reduction in tobacco use.

PMID- 14678066
TI  - Successful treatment with a nicotine lozenge of smokers with prior failure in
      pharmacological therapy.
AB  - AIMS: To assess the influence of unsuccessful past quit attempts using
      pharmacological treatment on smoking cessation when using a new nicotine lozenge.
      DESIGN: A double-blind, randomized, placebo-controlled trial. SETTING: Fifteen
      sites in the United Kingdom and the United States. PARTICIPANTS: A total of 1818
      smokers seeking smoking cessation treatment; 1145 had had previous
      pharmacological treatment for smoking cessation. INTERVENTION: Lozenge, 2 mg or 4
      mg (or matched placebo); a higher dose was assigned to smokers who smoked their
      first cigarette of the day within 30 minutes, a sign of dependence. Smokers
      received minimal instruction and counseling. MEASUREMENT: Outcome was 28-day, CO
      verified continuous abstinence at 6 weeks. Past use of medications was
      ascertained by self-report. FINDINGS: Lozenge was efficacious among smokers with
      prior pharmacotherapy as well as among those without such history. The effect of
      lozenge (versus placebo) was significantly greater among those with previous
      treatment experience, because previous treatment was associated with
      significantly poorer outcome on placebo, and active lozenge treatment corrected
      this imbalance. Lozenge efficacy was similar whether smokers had previously tried
      patch or acute forms of nicotine replacement therapy (gum, inhaler and spray),
      and also similar for past use of Zyban (bupriopion). CONCLUSIONS: Smokers with a
      history of past failure of pharmacological treatment have lower success rates
      without pharmacological treatment, but equally good outcomes with active lozenge
      treatment. Smokers who previously tried pharmacological treatments but resumed
      smoking should be encouraged to try quitting again with the new nicotine lozenge.

PMID- 14678067
TI  - Reduction of quantity smoked predicts future cessation among older smokers.
AB  - AIM: To examine whether smokers who reduce their quantity of cigarettes smoked
      between two periods are more or less likely to quit subsequently. STUDY DESIGN:
      Data come from the Health and Retirement Study, a nationally representative
      survey of older Americans aged 51-61 in 1991 followed every 2 years from 1992 to
      1998. The 2064 participants smoking at baseline and the first follow-up comprise
      the main sample. MEASUREMENTS: Smoking cessation by 1996 is examined as the
      primary outcome. A secondary outcome is relapse by 1998. Spontaneous changes in
      smoking quantity between the first two waves make up the key predictor variables.
      Control variables include gender, age, education, race, marital status, alcohol
      use, psychiatric problems, acute or chronic health problems and smoking quantity.
      FINDINGS: Large (over 50%) and even moderate (25-50%) reductions in quantity
      smoked between 1992 and 1994 predict prospectively increased likelihood of
      cessation in 1996 compared to no change in quantity (OR 2.96, P<0.001 and OR
      1.61, P<0.01, respectively). Additionally, those who reduced and then quit were
      somewhat less likely to relapse by 1998 than those who did not reduce in the 2
      years prior to quitting. CONCLUSIONS: Reducing successfully the quantity of
      cigarettes smoked appears to have a beneficial effect on future cessation
      likelihood, even after controlling for initial smoking level and other variables
      known to impact smoking cessation. These results indicate that the harm reduction
      strategy of reduced smoking warrants further study.

PMID- 14678068
TI  - Brief interventions for hazardous drinkers delivered in primary care are equally
      effective in men and women.
AB  - BACKGROUND: Despite the accumulated evidence on the efficacy of brief
      interventions in hazardous drinkers some ambiguity remains regarding their
      differential effectiveness by gender. METHODS: Meta-analysis of independent
      studies conducted in primary health care settings with a follow-up of 6-12 months
      which report results separately by gender. Two outcome measures were selected:
      the quantity of typical weekly alcohol consumption and the frequency of drinkers
      who reported consumption below hazardous levels after the intervention. RESULTS:
      Seven studies were included in the meta-analysis. The standardized effect sizes
      for the reduction of alcohol consumption were similar in men (d=- 0.25; 95% CI=-
      0.34 to -0.17) and women (d=- 0.26; 95% CI=- 0.38 to - 0.13). The odds ratios
      (OR) for the frequency of individuals who drank below harmful levels were also
      similar (four studies; OR for men=2.32; 95% CI=1.78-2.93; OR for women=2.31; 95%
      CI=1.60-3.17). The difference between genders was negligible. CONCLUSION: Our
      results support the equality of outcomes among men and women achieved by brief
      interventions for hazardous alcohol consumption in primary care settings.

PMID- 14678069
TI  - Different measures of alcohol consumption and risk of coronary heart disease and
      all-cause mortality: 11-year follow-up of the Whitehall II Cohort Study.
AB  - AIMS: To investigate the relationship between three measures of alcohol
      consumption obtained simultaneously in a large cohort and the validated risk of
      coronary heart disease and all-cause mortality during follow-up. DESIGN:
      Prospective cohort study with median follow-up of 11 years. SETTING: The
      Whitehall II Cohort Study: London-based civil service. PARTICIPANTS: A total of
      10,308 (33% female) civil servants aged 35-55 years at baseline (1985-88).
      MEASUREMENTS: Self-reported volume of alcohol consumed during past week,
      frequency of drinking over past year, usual amount consumed per drinking session.
      MAIN OUTCOME MEASURES: Coronary heart disease and all-cause mortality until 1999.
      FINDINGS: A U-shaped relationship was found between volume of alcohol consumed
      per week and outcome. Compared to those who drank moderately (10-80 g alcohol per
      week), non-drinkers and those drinking more than 248 g per week had approximately
      a twofold increased risk of mortality. The optimal frequency of drinking was
      between once or twice a week and daily, after adjustment for average volume
      consumed per week. Those drinking twice a day or more had an increased risk of
      mortality (male hazard ratio 2.44 95% CI 1.31-4.52) compared to those drinking
      once or twice a week. Drinking only once a month or only on special occasions had
      a 50% increased risk of mortality. The usual amount consumed per drinking session
      was not indicative of increased health risk in this cohort. CONCLUSIONS:
      Epidemiological studies should collect information on frequency of drinking in
      addition to average volume consumed in order to inform sensible drinking advice.

PMID- 14678070
TI  - Temporal stability of pathological scratchcard gambling among adult scratchcard
      buyers two years later.
AB  - AIMS: To estimate the 2-year cumulative incidence of pathological scratchcard
      gambling (PSG) among a representative sample of high-risk scratchcard buyers, to
      assess the 2-year temporal stability of PSG and scratchcard-related problems and
      to estimate the adjusted 1-year prevalence for PSG taking into account the
      temporal dynamics of this diagnosis. DESIGN: A prospective study with two
      assessments was applied to a non-proportional stratified random sample of 12,222
      adult scratchcard buyers in the Netherlands. A cost-effective design was used and
      only those scratchcard buyers (n=201) who had already experienced some
      scratchcard-related problems at initial assessment were followed-up 2 years
      later. PARTICIPANTS: Two independent cohorts of buyers with scratchcard-related
      problems were followed-up: a cohort of 173 potential problematic scratchcard
      gamblers (PPSG) at increased risk for PSG and a cohort of 28 pathological
      scratchcard gamblers. Incidence and prevalence estimates were calculated for the
      total sample of adult scratchcard buyers and for the Dutch adult population.
      FINDINGS: Of the PPSG group 6.72% (95% CI 2.30-8.90%) became addicted to
      scratchcards during the 2-year period. The 2-year cumulative incidence of PSG
      among Dutch adult scratchcard players was 0.24% (95% CI 0.16-0.34%). The
      stability of the Diagnostic and Statistical Manual 4th edition (DSM-IV) diagnosis
      of PSG ranged from 11.1% to 42.9%, depending on whether or not those lost to
      follow-up were considered to be cases of PSG. Taking into account the dynamics of
      this disorder, using the most conservative assumption, the adjusted 1-year
      prevalence of PSG for the total sample of adult scratchcard buyers was 0.33% (95%
      CI 0.23-0.45%). CONCLUSIONS: PSG proves to be a rare phenomenon among adult
      scratchcard buyers in the Netherlands. Both incidence and prevalence of the DSM
      IV diagnosis PSG were low. Stability of the DSM-IV diagnosis PSG, DSM-IV criteria
      and South Oaks Gambling Screening-S (SOGS-S) problems were low. Prevalence was
      stable over the time because incidence and recovery rates were very similar.

PMID- 14678071
TI  - Economic evaluation in addiction.

PMID- 14678072
TI  - More intensive treatment of addiction does benefit society.

PMID- 14678073
TI  - Estimates of economic gain from addiction treatment are only as good as the data:
      comments on McCollister & French.

PMID- 14678078
TI  - Screening for bacterial vaginosis to prevent preterm birth: assessing
      effectiveness and cost-effectiveness.

PMID- 14678079
TI  - Comment to a case report in this issue of Acta regarding placenta previa
      percreta.

PMID- 14678080
TI  - Effect of urinary trypsin inhibitor on potassium currents: fetus modulates
      membrane excitability by production of UTI.
AB  - BACKGROUND: Amniotic fluid contains a significant level of urinary trypsin
      inhibitor (UTI). Previously, we reported that UTI inhibits calcium influx of
      myometrium and it is effective in preventing uterine contraction. This study
      examined the effects of UTI upon potassium channels, which is important for
      membrane excitability. METHODS: Whole-cell patch-clamp recordings were performed
      in fibroblasts derived from human fetal skin. Potassium currents were recorded
      and the effects of exogenous UTI and/or cadmium determined. RESULTS:
      Tetraethylammonium sensitive potassium currents were elicited by step or ramp
      stimulations at depolarized membrane potentials (over +30 mV). Administration of
      1 micro M UTI significantly increased these potassium currents by 16.9%. When
      calcium channels were blocked by the administration of cadmium, UTI increased the
      rest of the potassium currents by 4.8%. This indicates that UTI increased calcium
      dependent potassium currents by 94.8% but only increased voltage-dependent
      potassium currents by 4.8%. CONCLUSIONS: Urinary trypsin inhibitor is a
      physiological substance of fetal origin that modulates calcium-dependent and
      voltage-dependent potassium channels. These data suggest that UTI is capable of
      regulating the membrane properties of the fetal and myometrial cells in contact
      with amniotic fluid.

PMID- 14678081
TI  - Inhibitory effects of SR 49059 on oxytocin-and vasopressin-induced uterine
      contractions in non-pregnant women.
AB  - BACKGROUND: Compounds that block uterine oxytocin and vasopressin V1a receptors
      have a therapeutic potential in preterm labor and primary dysmenorrhoea. The
      orally active vasopressin V1a receptor antagonist, SR49059, inhibits the effect
      of vasopressin on human uterine activity in vivo, but the influence on the
      response to oxytocin is unknown. METHODS: In a placebo-controlled, double-blind,
      parallel-group, four-dose comparison, the inhibitory effect of SR 49059 on
      oxytocin- and vasopressin-induced uterine contractions in humans was
      investigated. Sixteen healthy female subjects, who had previously undergone
      sterilization with tubal ligation, participated in intrauterine pressure
      recordings at one of the first 3 days of bleeding of two menstrual cycles.
      Intravenous bolus injections of 10 pmol/kg body weight of vasopressin (Period 1)
      and of 50 pmol/kg body weight of oxytocin (Period 2) were given 1 h before and 1,
      2 and 4 h after oral administration of 0 (placebo), 25, 75 or 200 mg of SR 49059.
      The area between the recording curve and zero level of intrauterine pressure
      (AUC) was calculated. Vital signs as well as urine and plasma safety parameters
      were measured. The plasma concentrations of oxytocin, vasopressin and the study
      drug were also estimated. RESULTS: The plasma concentrations of SR 49059 appeared
      to be dose related, with mean maximal values of 62.0, 163.7 and 468.0 ng/ml in
      the 25, 75 and 200 mg dose groups, respectively, in Period 1 with vasopressin and
      34.4, 116.7 and 418.0 ng/mL, respectively, in Period 2 with oxytocin. Tmax was
      observed at about 1 h. The cumulative AUC over 50 min after vasopressin injection
      per se was significantly higher than that after oxytocin in spite of a five times
      lower dose and lower plasma concentrations. Pretreatment by SR 49059 caused a
      dose-related reduction in AUCs for vasopressin, whereas no such effect was seen
      for oxytocin. With vasopressin as an agonist, a lower diastolic blood pressure
      was observed in all SR 49059 treatment groups, but not with oxytocin.
      CONCLUSIONS: The much higher potency of vasopressin compared with oxytocin on
      uterine activity in non-pregnant women at menstruation was confirmed. SR 49059
      dose-dependently inhibits vasopressin-induced contractions, whereas such an
      effect was not seen with the present doses of SR 49059 and oxytocin. A marked
      reduction by SR 49059 of diastolic blood pressure after vasopressin injection was
      observed, indicating an inhibition by this compound of vascular vasopressin
      receptors.

PMID- 14678082
TI  - Norepinephrine, adrenocorticotropin, cortisol and beta-endorphin in women
      suffering from fear of labor: responses to the cold pressor test during and after
      pregnancy.
AB  - BACKGROUND: Women suffering from fear of labor have reduced pain tolerance during
      a cold pressor test (CPT) during and after pregnancy. METHODS: We compared levels
      of norepinephrine, adrenocorticotropin (ACTH), cortisol and beta-endorphin before
      and during the CPT up to 60 min in 20 normotensive women with and 20 without fear
      of labor at 37.4 +/- 0.2 (mean +/- SE) gestational weeks and at 41.9 +/- 1.6
      weeks after delivery. RESULTS: Baseline levels of norepinephrine in the pregnant
      fear group (1.63 +/- 0.18 nmol/L) were higher (p = 0.068) than in controls (1.38
      +/- 0.14 nmol/L) but after delivery they were lower in the fear group (1.75 +/-
      0.31 nmol/L vs. 2.31 +/- 0.26 nmol/L, p = 0.064). ACTH, cortisol and beta
      endorphin did not differ between pregnant and nonpregnant groups. The CPT caused
      a 28.4% smaller response in norepinephrine in the pregnant fearful women than in
      controls, whereas the responses of ACTH and beta-endorphin were similar between
      groups during and after pregnancy. The CPT caused no significant response in
      cortisol. Pregnant fearful women had higher diastolic blood pressure (85.6 +/-
      4.5 mmHg, mean +/- SE) than the controls (74.9 +/- 3.4 mmHg, p = 0.065).
      CONCLUSIONS: Women with fear of labor were characterized by changes in
      norepinephrine but not in ACTH, cortisol or beta-endorphin before and during the
      CPT, indicating a normal pituitary-adrenal axis function.

PMID- 14678083
TI  - Cost-effectiveness of screening and treatment for bacterial vaginosis in early
      pregnancy among women at low risk for preterm birth.
AB  - BACKGROUND: Bacterial vaginosis (BV) is an important risk factor for preterm
      birth. BV is detected in 10-30% of pregnant women and is often asymptomatic.
      Treatment of BV during pregnancy seems to reduce the risk of preterm delivery
      among high-risk women. We performed a cost-effectiveness analysis of screening
      and treatment for BV in early pregnancy among asymptomatic women at low risk for
      preterm delivery. METHODS: A decision tree was built with two arms. For the
      screening (and treatment) arm the probabilities were derived from our earlier
      randomized trial on screening and treatment for BV, consisting of BV-positive
      women treated with intravaginal clindamycin cream or placebo and also of BV
      negative pregnant women. The probabilities of outcomes among these women were
      collected from antenatal clinic records and hospital records, and for the no
      screening arm mainly from the Finnish Perinatal Statistics. The outcomes
      considered were preterm delivery, mode of delivery, peripartum infections and
      postpartum complications. The unit costs associated with these outcomes were
      mainly based on disease-related groups (DRGs). No-screening was compared with two
      screening programs (one with clindamycin, the other with metronidazole treatment)
      and subjected to sensitivity analyses. RESULTS: There was no significant
      difference between screening and no-screening strategies in the costs and in the
      rate of preterm deliveries but the screening strategy produced significantly
      fewer peripartum infections and postpartum complications. Sensitivity analyses
      suggested that the screening strategy may become cost-saving if the rate of
      preterm deliveries exceeds 3%. CONCLUSION: Screening and treatment for BV in
      early pregnancy may not reduce costs compared to no-screening in a population at
      low risk for preterm birth but would produce, at the same cost, more health
      benefits in terms of fewer peripartum infections and postpartum complications.
      However, it may be cost-saving if the rate of preterm deliveries is higher than
      3%.

PMID- 14678084
TI  - Second- and third-trimester serum levels of placental proteins in preeclampsia
      and small-for-gestational age pregnancies.
AB  - BACKGROUND: Poor placentation may perpetuate preeclampsia, but the presence of a
      major placental pathology has been questioned in cases of preeclampsia where the
      newborn has an appropriate birthweight for gestational age. On the other hand,
      poor placentation is also observed in the absence of preeclampsia, in pregnancies
      with small-for-gestational-age (SGA) fetuses. In late gestation, maternal serum
      levels of placental protein hormones are changed in both preeclampsia and SGA,
      but no longitudinal pre-onset studies are available for pregnancy-associated
      plasma protein A (PAPP-A), pregnancy-specific beta1-glycoprotein (SP1) or human
      placental lactogen (HPL). METHODS: In a nested case-control study we compared
      maternal serum levels of PAPP-A, SP1, HPL and placenta growth factor (PLGF) at
      17, 25 and 33 weeks in pregnancies developing preeclampsia without fetal growth
      restriction (n = 28), or characterized by a growth-retarded fetus (n = 25), with
      gestation-matched controls (n = 65). The proteins were quantified using
      microplate enzyme immunometric assays and the serum levels at 17, 25 and 33 weeks
      compared between the three groups by nonparametric statistical tests. RESULTS: In
      pregnancies with subsequent preeclampsia PAPP-A, SP1, HPL and PLGF were reduced
      at 17 weeks of gestation whereas at 25 and 33 weeks only PLGF remained below the
      controls. In growth-restricted pregnancies PAPP-A, SP1 and HPL were reduced at 17
      weeks, and only HPL continued to be strongly affected thereafter. CONCLUSION: The
      reduced serum levels of the placental proteins PAPP-A, SP1 and HPL in the early
      second trimester (17 weeks) in pregnancies with subsequent preeclampsia or with
      fetal growth restriction involve an underlying role for the placenta in either
      pathology independent from the other.

PMID- 14678085
TI  - Repeated random blood glucose measurements as universal screening test for
      gestational diabetes mellitus.
AB  - BACKGROUND: To determine the value of repeated random blood glucose (R-B-glucose)
      measurements alone or in combination with traditional risk factors [family
      history of diabetes, obesity, prior large-for-gestational-age (LGA) infant or
      prior gestational diabetes mellitus (GDM)] to predict the outcome of the oral
      glucose tolerance test (OGTT). METHODS: A prospective population-based study was
      undertaken in a Swedish county. All pregnant nondiabetic women (n = 4918)
      visiting the maternal health care clinics over a 2-year period were offered a 75
      g OGTT in gestational weeks 28-32. Traditional risk factors and values of
      repeated R-B-glucose measurements were registered, as well as the results of the
      OGTT, in terms of fasting B-glucose and 2-h B-glucose. RESULTS: A total of 3616
      women (73.5%) had an OGTT. Of these, 1.7% had GDM, 1.3% impaired glucose
      tolerance (IGT) and 0.4% diabetes mellitus (DM). An R-B-glucose cut-off level >
      or =8.0 mmol/L as the only indicator for an OGTT was optimal for detecting GDM
      with regard to sensitivity (47.5%) and specificity (97.0%). It has the same
      sensitivity for detecting GDM as using traditional risk factors, but reduces the
      need to carry out the OGTT from 15.8% to 3.8% of the population. Combined with
      prior LGA infant or prior GDM as indications for the OGTT in the present study,
      all women with DM and 44.7% of those with IGT will be identified. Only 7.3% of
      the population will have to take the OGTT. CONCLUSION: A random B-glucose level >
      or = 8.0 mmol/L prior LGA infant or prior GDM as an indicator for taking the OGTT
      is a simple and effective first step in a two-step screening model for GDM.

PMID- 14678086
TI  - Mode of delivery in pregnancies with suspected fetal growth restriction following
      induction of labor with vaginal prostaglandin E2.
AB  - BACKGROUND: Many fetuses below the 10th percentile for gestational age are
      uncompromised. We aimed to evaluate the mode of delivery and immediate neonatal
      outcome in pregnancies with suspected fetal growth restriction (FGR) and normal
      antenatal assessment following induction of labor with vaginal application of
      prostaglandin E2 (PGE2). METHODS: Ninety women with suspected FGR (sonographic
      estimated fetal weight < 10th percentile) with normal oxytocin contraction test
      (OCT), biophysical profile (BPP) and reassuring fetal heart rate underwent
      induction of labor with vaginal application of PGE2 tablets. The findings were
      compared with 115 women admitted for induction of labor because of decreased
      fetal movement (group 2) and with 510 women with normal spontaneous onset of
      labor (group 3). RESULTS: There were no between-group differences in mean
      maternal age, gravidity, parity, nulliparity rate, number of tablets used or rate
      of patients receiving more than one PGE2 application. The rate of cesarean
      section (CS) in the study group (8.9%) was similar to the rate in groups 2 and 3
      (14.8% and 9.0%, respectively). The incidence of nonreassuring fetal heart rate
      pattern leading to cesarean delivery was higher in the study group, but the rate
      of low 5-min Apgar scores (< 7) was similar in all groups. A logistic regression
      model and forward likelihood analysis yielded no single significant variable
      associated with increased risk of cesarean delivery. CONCLUSIONS: In selected
      cases of suspected FGR with reassuring fetal heart rate and normal OCT and BPP,
      induction of labor with vaginal PGE2 may yield a similar immediate fetal outcome
      and CS rate as in uncomplicated, induced or spontaneous deliveries.

PMID- 14678087
TI  - The Kola Birth Registry and perinatal mortality in Moncegorsk, Russia.
AB  - BACKGROUND: A population-based birth registry has been set up for the Arctic town
      of Moncegorsk in north-western Russia. In this investigation, the quality and the
      content of the registry are assessed and the perinatal mortality (PM) rates in
      the period 1973-97 estimated. MATERIAL AND METHOD: Enrollment in the Kola Birth
      Registry (KBR) involved the retrospective inclusion of all births with at least
      28 weeks of gestation in Moncegorsk in the period 1973-97. The data in the
      registry were assessed for data entry errors, completeness of data and population
      coverage. The annual PM rates were estimated for live- and stillborns with at
      least 28 weeks of gestation. RESULTS: The KBR contains detailed information about
      the newborn, delivery, pregnancy and mother for 21 214 births by women from
      Moncegorsk, covering at least 96% of all the births by the population in the
      period studied. No records were missing data for gender and birth date of the
      newborn, and more than 99.9% of the records contained data about gestational age
      and birthweight. Data concerning the mothers' employment were missing in 0.4% of
      the records. The annual PM rate fell from more than 20 to less than 10 deaths per
      1000 births during this period. CONCLUSION: The KBR provides an extensive data
      source useful for case-control and register-based prospective studies, and
      constitutes the first such compilation in Russia. The homogeneity of the
      population in Moncegorsk makes it advantageous for epidemiological
      investigations. The PM rate in Moncegorsk was lower than the overall rate in
      Russia.

PMID- 14678089
TI  - Maternal risks and perinatal outcome in a Danish national cohort of 1005 twin
      pregnancies: the role of in vitro fertilization.
AB  - BACKGROUND: Twin pregnancies constitute 25% of all in vitro fertilization (IVF)
      and intracytoplasmic sperm injection (ICSI) pregnancies. There is a lack of
      knowledge on maternal risks and perinatal outcome of IVF/ICSI twin pregnancies.
      METHODS: National survey by questionnaire (n = 1769). The study population
      consisted of all IVF/ICSI twin mothers (n = 266) and the two control groups of
      all IVF/ICSI singleton mothers (n = 764) and non-IVF/ICSI twin mothers (n = 739)
      who delivered in Denmark in 1997. The response rate was 89% among IVF twin
      mothers and overall 81%. RESULTS: In terms of maternal risks and perinatal
      outcome no significant differences were observed between IVF/ICSI twin and non
      IVF/ICSI twin pregnancies after stratification for maternal age and parity.
      Nevertheless, IVF/ICSI twin mothers were more frequently on sick leave (OR 2.5,
      95% CI 1.5-4.0) and hospitalized (OR 1.9, 95% CI 1.3-2.8) during pregnancy.
      Compared with IVF/ICSI singleton pregnancies, IVF/ICSI twin pregnancies were
      characterized by a higher incidence of preeclampsia (OR 2.4, 95% CI 1.5-4.2) and
      a higher frequency of sick leave (OR 6.8, 95% CI 4.4-10.5) and hospitalizations
      during pregnancy (OR 3.5, (95% CI 2.5-4.9); moreover, mean birthweight (p <
      0.001) and gestational age (p < 0.001) were lower. No differences were observed
      in the incidence of pregnancy-induced hypertension and gestational diabetes
      between IVF/ICSI twin and singleton pregnancies. CONCLUSION: Although this
      population study indicates that maternal risks in IVF/ICSI twin pregnancies are
      comparable with non-IVF/ICSI twin pregnancies, the IVF/ICSI twin mothers were
      more likely to be on sick leave or hospitalized during pregnancy. Furthermore,
      maternal risks were higher and obstetric outcome poorer in IVF/ICSI twin vs.
      IVF/ICSI singleton pregnancies.

PMID- 14678090
TI  - The influence of body mass index on the prevalence of complications after vaginal
      and abdominal hysterectomy.
AB  - AIM OF STUDY: To investigate the association between obesity and peri- or
      postoperative complications after hysterectomy for nonmalignant bleeding
      disorders. MATERIAL AND METHODS: Data from 444 vaginal hysterectomies and 503
      abdominal hysterectomies indicated by benign bleeding disorders were drawn from a
      regional database. Data on peri- or postoperative complications and postoperative
      stay were related to preoperative body mass index (BMI). RESULTS: Obesity was
      related to longer operation time for vaginal as well as abdominal hysterectomy
      and to large perioperative blood loss for vaginal hysterectomy only. No
      association was found between BMI and serious complications such as ileus,
      infection or hematomas except for a higher prevalence of wound hematoma after
      abdominal hysterectomy in underweight and normal weight patients. Neither was any
      association found between BMI and use of blood transfusion, reoperation or
      prolonged postoperative stay. CONCLUSION: Vaginal and abdominal hysterectomy have
      a significant risk of complications, but obese patients did not experience an
      increased risk of serious morbidity compared to normal weight women. Obesity per
      se is not a contraindication of vaginal or abdominal hysterectomy in otherwise
      healthy women.

PMID- 14678088
TI  - Obstetric outcomes after cervical ripening by multiple doses of vaginal
      prostaglandin E2.
AB  - AIM: The study was designed to investigate the delivery outcome in women who
      required vaginal prostaglandin E2 for cervical priming prior to labor induction.
      MATERIALS AND METHODS: This retrospective cohort study included all singleton
      term deliveries that required labor induction over a 3-year period. Incidence and
      indications of obstetric interventions were compared among women who required
      different doses of vaginal prostaglandin E2 for cervical priming and who had
      induction by amniotomy and oxytocin infusion. RESULTS: Of 706 deliveries, 411 had
      favorable Bishop's scores and no vaginal prostaglandin E2 for cervical priming
      was required (group A); 268 required one or two doses of vaginal prostaglandin E2
      for cervical priming (group B); and 27 required three or more doses (group C).
      The incidence of cesarean section was significantly higher in group C (48.1%)
      than in group A (19.0%) and group B (16.4%). The difference remained
      statistically significant when primiparous and multiparous women were analyzed
      separately. The risk of obstetric intervention was particularly high in
      primiparous women in group C (58.8% required emergency cesarean section and 23.5%
      had instrumental delivery). There was an increased frequency of all major
      indications for cesarean section in group C. CONCLUSION: The risk of emergency
      cesarean section was higher in women who required more than two doses of vaginal
      prostaglandin E2 for cervical priming compared to induction by one or two doses
      of vaginal prostaglandin E2 or by amniotomy and oxytocin infusion. These women
      should be informed regarding the high risk of intrapartum cesarean section, and
      the option of alternative methods of induction or elective cesarean section
      should be made available.

PMID- 14678091
TI  - Management of postmenopausal bleeding in Sweden: a need for increased use of
      hydrosonography and hysteroscopy.
AB  - BACKGROUND: The objective was to determine how postmenopausal bleeding (PMB) is
      managed in Sweden today, and to relate the findings to a new evidence-based
      algorithm for the management of PMB. METHODS: A questionnaire regarding the role
      of ultrasound and the use of different endometrial biopsy methods in the
      management of PMB was sent to all 61 gynecologic departments in Sweden. RESULTS:
      Fifty-nine of the 61 departments (97%) satisfactorily answered the questionnaire.
      Ultrasound was either always (n = 54, 92%) or most commonly (n = 5, 8%) used in
      the diagnostic work-up of PMB. In women with endometrial thickness < or =4 mm, 18
      of the departments (31%) routinely sampled the endometrium; 12 (15%) followed the
      women with ultrasound; three (5%) did both sampling and follow-up with
      ultrasound; and the remaining 29 (49%) used expectant management (i.e. no biopsy
      or routine follow-up). In women with endometrium > or =5 mm, hydrosonography was
      performed routinely in two departments (3%), occasionally in 37 departments
      (63%), and never in 20 departments (34%). In women with endometrium > or =5 mm,
      endometrial biopsy was obtained routinely by Endorette/Pipelle in 39 departments
      (66%), while in 26 departments (44%) operative hysteroscopy was never performed.
      CONCLUSION: More than one-third of the gynecologic departments in Sweden never
      perform hydrosonography to rule out focal lesions or operative hysteroscopy for
      the removal of such lesions. Hydrosonography and hysteroscopy have a central role
      in the new guidelines for the management of PMB. Therefore, a need exists to
      broaden the use of hydrosonography and hysteroscopy.

PMID- 14678092
TI  - Radiotherapy at a young age reduces uterine volume of childhood cancer survivors.
AB  - BACKGROUND: In contrast to chemotherapy, previous irradiation of the uterus
      carries an increased risk of an adverse pregnancy outcome. Conflicting results
      exist as regards the ability of the uterus to increase in volume following
      radiotherapy-induced damage. We measured uterine volume in a cohort of childhood
      cancer survivors, and assessed uterine response to a high-dose estrogen
      replacement regimen. METHODS: Uterine volume was assessed by transvaginal
      sonography in 100 childhood cancer survivors. Three patients with ovarian failure
      and severely reduced uterine volume following abdominal or pelvic irradiation
      were treated with percutaneous estradiol 150 microg/24 h for three cycles, and
      transvaginal uterine sonography was repeated monthly. RESULTS: Uterine volume was
      significantly reduced in nulliparous patients who had received direct uterine
      irradiation (n = 13; median 13 mL, range 1-52 mL) compared with nulliparous
      patients who had received chemotherapy only (n = 37; 47 mL, 22-88), radiotherapy
      above the diaphragm (n = 17; 40 mL, 24-61), or radiotherapy below the diaphragm
      not directly involving the uterus (n = 13; 34 mL, 8-77) (p < 0.02 in all
      comparisons). Among nulliparous patients a significant correlation was found
      between age at direct uterine irradiation and uterine volume (r = 0.78, p =
      0.002). No significant improvement in uterine volume, endometrial thickness or
      uterine artery blood flow was observed in three hypogonadal patients in response
      to high-dose estrogen replacement therapy. CONCLUSIONS: Our results indicate that
      cytotoxic treatment in childhood does not affect adult uterine size. In contrast,
      uterine irradiation at a young age reduces adult uterine volume. The radiotherapy
      induced damage is probably irreversible.

PMID- 14678093
TI  - Dietary supplementation with L-arginine or placebo in women with pre-eclampsia.
AB  - BACKGROUND: To investigate the effect of dietary intake of the NO-donor L
      arginine on the diastolic blood pressure in women with pre-eclampsia. METHODS: A
      randomized double-blind study was designed to compare the effect of L-arginine
      and placebo in pre-eclamptic women with gestational length ranging from 28+0 to
      36+0 weeks. The women received orally 12 g of L-arginine or placebo daily for up
      to 5 days. The primary end-point was to identify a difference in diastolic blood
      pressure alteration between the two groups after 2 days of intervention.
      Secondary end-points included the interval from study start to delivery, the
      proportion of women delivered after 2, 5 or 10 days from treatment start and mean
      birth weight. RESULTS: There was no statistically significant alteration in
      diastolic blood pressure in the L-arginine group compared with the placebo group
      after 2 days of treatment (p = 0.4). No differences in the proportions of women
      delivered by day 2, 5 or 10 after study start, in the mean interval from study
      start to delivery, or in mean birth weight percentile were observed between the
      two groups. CONCLUSIONS: Oral L-arginine supplementation did not reduce mean
      diastolic blood pressure after 2 days of treatment compared with placebo in pre
      eclamptic patients with gestational length varying from 28 to 36 weeks. Whether L
      arginine treatment could be clinically beneficial for the mother or the fetus if
      started earlier in the disease process than for the women in our study remains to
      be seen.

PMID- 14678094
TI  - Unsuccessful medical treatment of cesarean scar ectopic pregnancy with systemic
      methotrexate: a report of two cases.

PMID- 14678095
TI  - Cervical pregnancy after in vitro fertilization and embryo transfer successfully
      treated with methotrexate and intracervical injection of vasopressin.

PMID- 14678096
TI  - Spontaneous uterine rupture following intercourse.

PMID- 14678097
TI  - Cesarean section by transfundal approach for placenta previa percreta attached to
      anterior uterine wall in a woman with a previous repeat cesarean section: case
      report.

PMID- 14678099
TI  - Congenital short QT syndrome and implantable cardioverter defibrillator
      treatment: inherent risk for inappropriate shock delivery.
AB  - INTRODUCTION: A congenital short QT interval constitutes a new primary electrical
      abnormality associated with syncope and/or sudden cardiac death. We report on the
      initial use of implantable cardioverter defibrillator (ICD) therapy in patients
      with inherited short QT interval and discuss sensing abnormalities and detection
      issues. METHODS AND RESULTS: In five consecutive patients from two unrelated
      European families who had structurally normal hearts, excessively shortened QT
      intervals, and a strong positive family history of sudden cardiac death, ICDs
      were placed for primary and secondary prevention. Mean QT intervals were 252 +/-
      13 ms (QTc 287 +/- 13 ms). Despite normal sensing behavior during intraoperative
      and postoperative device testing, 3 of 5 patients experienced inappropriate shock
      therapies for T wave oversensing 30 +/- 26 days after implantation. Programming
      lower sensitivities and decay delays prevented further inappropriate discharges.
      CONCLUSION: The congenital short QT syndrome constitutes a new clinical entity
      with an increased risk for sudden cardiac death. Currently, ICD treatment is the
      only therapeutic option. In patients with short QT interval and implanted ICD,
      increased risk for inappropriate therapy is inherent due to the detection of
      short-coupled and prominent T waves. Careful testing of ICD function and
      adaptation of sensing levels and decay delays without sacrificing correct
      arrhythmia detection are essential.

PMID- 14678100
TI  - Inappropriate implantable cardioverter defibrillator therapy in the short QT
      syndrome: old problem in a new disease.

PMID- 14678101
TI  - Development and validation of an ECG algorithm for identifying the optimal
      ablation site for idiopathic ventricular outflow tract tachycardia.
AB  - INTRODUCTION: Idiopathic ventricular outflow tract tachycardia or premature
      ventricular contractions (OT-VTs) can originate from several different sites in
      the outflow tract, including the left ventricular (LV) endocardium and
      epicardium. The aims of this study were (1) to develop an ECG algorithm to
      predict the origin of OT-VT and (2) to test prospectively the accuracy of the
      algorithm. METHODS AND RESULTS: An algorithm was developed by correlating the 12
      lead ECG findings with the catheter ablation site in 80 patients with OT-VT. The
      ECG characteristics of the QRS complex during the arrhythmia were analyzed. The
      catheter sites were verified by multi-plane fluoroscopy. The outflow tract was
      classified into six subdivisions: right ventricular (RV) septum, RV free wall, RV
      near the His-bundle region, LV endocardium, left sinus of Valsalva (LSV), and LV
      epicardium remote from the LSV. An OT-VT originating from the LV epicardium
      remote from the LSV was defined as an OT-VT in which the earliest ventricular
      activation was recorded at the LSV and radiofrequency ablation from the LSV
      failed. This algorithm subsequently was tested prospectively in 88 patients.
      Overall sensitivity was 88% and specificity was 95%. The positive and negative
      predictive values were 88% and 96%, respectively. CONCLUSION: We describe a new
      ECG algorithm having a high sensitivity and specificity to identify the optimal
      ablation site for idiopathic ventricular outflow tachycardia or premature
      ventricular contractions.

PMID- 14678102
TI  - The electrocardiogram: another three-dimensional mapping system for ablation of
      outflow tract tachycardias.

PMID- 14678103
TI  - Left atrial radiofrequency ablation during cardiac surgery in patients with
      atrial fibrillation.
AB  - INTRODUCTION: Intraoperative left atrial radiofrequency (RF) ablation recently
      has been suggested as an effective surgical treatment for atrial fibrillation
      (AF). The aim of this study was to verify the outcome of this technique in a
      controlled multicenter trial. METHODS AND RESULTS: One hundred three consecutive
      patients (39 men and 65 women; age 62 +/- 11 years) affected by AF underwent
      cardiac surgery and RF ablation in the left atrium (RF group). The control group
      consisted of 27 patients (6 men and 21 women; age 64 +/- 7 years) with AF who
      underwent cardiac surgery during the same period and refused RF ablation. Mitral
      valve disease was present in 89 (86%) and 25 (92%) patients, respectively (P =
      NS). RF endocardial ablation was performed in order to obtain isolation of both
      right and left pulmonary veins, a lesion connecting the previous lines, and a
      lesion connecting the line encircling the left veins to the mitral annulus. Upon
      discharge from the hospital, sinus rhythm was present in 65 patients (63%) versus
      5 patients (18%) in the control group (P < 0.0001). Mean time of cardiopulmonary
      bypass was longer in the RF group (148 +/- 50 min vs 117 +/- 30 min, P = 0.013).
      The complication rate was similar in both groups, but RF ablation-related
      complications occurred in 4 RF group patients (3.9%). After a mean follow-up of
      12.5 +/- 5 months (range 4-24), 83 (81%) of 102 RF group patients were in stable
      sinus rhythm versus 3 (11%) of 27 in the control group (P < 0.0001). The success
      rate was similar among the four surgical centers. Atrial contraction was present
      in 66 (79.5%) of 83 patients in the RF group in sinus rhythm. CONCLUSION:
      Endocardial RF left atrial compartmentalization during cardiac surgery is
      effective in restoring sinus rhythm in many patients. This technique is easy to
      perform and reproducible. Rare RF ablation-related complications can occur.
      During follow-up, sinus rhythm persistence is good, and biatrial contraction is
      preserved in most patients.

PMID- 14678104
TI  - Total atrioventricular nodal ablation increases atrial fibrillation burden in
      patients with paroxysmal atrial fibrillation despite continuation of
      antiarrhythmic drug therapy.
AB  - INTRODUCTION: Total atrioventricular nodal (TAVN) ablation and pacing is an
      accepted and safe treatment for patients with drug-refractory paroxysmal atrial
      fibrillation (AF). Many patients develop permanent AF within the first 6 months
      after TAVN ablation. This usually is ascribed to the cessation of antiarrhythmic
      drug therapy. We hypothesized that TAVN ablation itself creates an atrial
      substrate prone to AF. METHODS AND RESULTS: Patients participating in the Atrial
      Pacing Periablation for Paroxysmal Atrial Fibrillation (PA3) study who remained
      on stable antiarrhythmic drug therapy throughout follow-up were included in this
      analysis. AF burden and the development of persistent AF in the preablation
      period were compared to two consecutive postablation periods. Echocardiographic
      changes also were evaluated. Twenty-two patients remained on stable drug therapy
      (9 men and 13 women, age 59 +/- 3 years). One patient developed persistent AF
      preablation compared to 10 postablation (P < 0.05). AF burden preablation was 3.0
      +/- 1.2 hours/day and increased to 10.4 +/- 2.2 hours/day and 11.8 +/- 2.3
      hours/day in the two postablation follow-up periods (P < 0.05). In patients with
      fractional shortening (FS) >30% prior to ablation, FS decreased significantly
      from 39.4% +/- 1.3% to 36.4%+/- 1.7% (P < 0.05). In contrast, in patients with a
      FS < or =30% prior to ablation, FS increased from 27% +/- 0.8% to 33.6 +/- 1.7%
      (P < 0.05). CONCLUSION: TAVN ablation increases AF burden and facilitates the
      development of persistent AF in patients with paroxysmal AF despite the
      continuation of antiarrhythmic drugs. Loss of AV and/or interventricular
      synchrony may lead to altered cardiac hemodynamics resulting in atrial stretch
      and increasing AF burden.

PMID- 14678105
TI  - Delineation of intra-atrial reentrant tachycardia circuits after mustard
      operation for transposition of the great arteries using biatrial electroanatomic
      mapping and entrainment mapping.
AB  - INTRODUCTION: Intra-atrial reentrant tachycardia (IART) circuits after Mustard
      operation remain incompletely understood due to the complex atrial anatomy after
      extensive surgical procedures. The aim of this study was to delineate IART
      circuits and their relations to the individual anatomic boundaries in Mustard
      patients. METHODS AND RESULTS: Twelve patients (10 men and 2 women; age 29 +/-
      4.6 years) with atrial tachyarrhythmias after Mustard operation were included in
      this study. During 14 IARTs and 2 focal atrial tachycardias, electroanatomic
      mapping and entrainment mapping were performed in both the systemic venous atrium
      and the pulmonary venous atrium. The latter was accessed via a retrograde
      transaortic approach. Thirteen IARTs used a single-loop reentrant circuit, and 1
      IART used a dual-loop reentrant circuit. Ten (77%) of 13 single-loop reentrant
      circuits used the tricuspid annulus (TA) as their central barrier. The remaining
      3 IARTs rotated around the inferior vena cava (IVC) (n = 2) or ostium of the
      right upper pulmonary vein (n = 1). In 6 (60%) of the 10 peritricuspid IARTs,
      both pulmonary venous atrium and systemic venous atrium components of the mid
      portion of the TA-IVC isthmus were demonstrated to be part of the reentry.
      Overall, 12 (86%) of 14 IARTs in 10 patients were successfully ablated by
      bridging two barriers that constrained the reentrant circuit. Eight (80%) of 10
      peritricuspid circuits were abolished by linear ablation connecting the TA to the
      IVC (n = 4), incisional scar (n = 2), patch (n = 1), and atriotomy (n = 1).
      CONCLUSIONS: In Mustard patients, the TA serves as the most frequent central
      barrier of IART. Biatrial electroanatomic mapping combined with entrainment
      mapping facilitates delineation of IART circuits in relation to their anatomic
      barriers and enables the design of individual ablation strategies to achieve high
      success.

PMID- 14678106
TI  - Identification of pulmonary vein potentials by differential site atrial pacing in
      patients with paroxysmal atrial fibrillation: enhanced detection by pulmonary
      vein pacing.
AB  - INTRODUCTION: Pulmonary vein (PV) isolation may cure paroxysmal atrial
      fibrillation (PAF); however, identification of PV potentials may be difficult in
      sinus rhythm. Studies have suggested that atrial pacing may improve the
      identification of PV potentials. METHODS AND RESULTS: In 25 consecutive patients
      who underwent PV isolation for PAF, the results of pacing from the distal PV,
      distal and proximal coronary sinus, and high right atrium compared to sinus
      rhythm were analyzed to determine the most effective pacing site for
      identification of PV potentials. The percentage of confirmed PV potentials and
      the longest interval between atrial and PV potentials in each PV were compared
      during differential site pacing and sinus rhythm. PV potentials were confirmed in
      63 (82%) of 77 PVs that could be mapped during the complete pacing protocol and
      during sinus rhythm. Distal PV pacing identified significantly more PV potentials
      (left upper pulmonary vein [LUPV] 100%, left lower pulmonary vein [LLPV] 84%,
      right upper pulmonary vein [RUPV] 80%, right lower pulmonary vein [RLPV] 53%)
      compared to other pacing sites and sinus rhythm. Among atrial pacing sites, those
      ipsilateral to the PV being mapped were the most effective for identifying PV
      potentials. The intervals between atrial and PV potentials were significantly
      longer during distal PV pacing than pacing at other sites (LUPV 81.6 +/- 26.2 ms,
      LLPV 61.4 +/- 26.1 ms, RUPV 59.7 +/- 33.2 ms, RLPV 39.7 +/- 26.7 ms). CONCLUSION:
      (1) Distal PV pacing was most effective for identifying PV potentials. (2) The
      interval between atrial and PV potentials was longest during distal PV pacing.

PMID- 14678107
TI  - How to discriminate pulmonary vein potentials from atrial potentials.

PMID- 14678108
TI  - Para-Hisian entrainment: a novel pacing maneuver to differentiate orthodromic
      atrioventricular reentrant tachycardia from atrioventricular nodal reentrant
      tachycardia.
AB  - INTRODUCTION: Para-Hisian pacing during sinus rhythm can help to identify the
      presence of an accessory pathway (AP). In this maneuver, the retrograde
      activation time and pattern are compared during capture and loss-of-capture of
      the His bundle while pacing from a para-Hisian position. However, identification
      of a retrograde AP does not necessitate that it is operative during the
      tachycardia of interest; conversely, slowly conducting or "distant" bypass tracts
      may not be identified. We evaluated the utility of entrainment or resetting of
      tachycardias from the para-Hisian position to help distinguish atrioventricular
      nodal reentrant tachycardia (AVNRT) from orthodromic atrioventricular tachycardia
      (AVRT). METHODS AND RESULTS: Para-Hisian entrainment/resetting was evaluated in
      50 patients: 33 with AVNRT and 17 with AVRT. The maneuvers were performed using a
      standard quadripolar catheter placed at the His position: low output for right
      ventricular (RV) capture and high output for both RV and His capture. The
      retrograde atrial activation sequence, SA interval (interval from stimulus to
      earliest retrograde atrial activation), and "local" VA interval (interval between
      the ventricular and atrial electrograms at the site of earliest retrograde atrial
      activation) were compared between His and His/RV capture. The DeltaSA was > 40 ms
      in patients with AVNRT and was < 40 ms in all but one patient with AVRT. In
      concert with the DeltaSA interval, the DeltaVA interval was able to fully define
      the mechanism of the tachycardia in all patients studied. CONCLUSION: Para-Hisian
      entrainment/resetting can determine the course of retrograde conduction operative
      during narrow complex tachycardias. It is a useful diagnostic maneuver in
      differentiating AVNRT and orthodromic AVRT.

PMID- 14678109
TI  - Role of the coronary sinus in maintenance of atrial fibrillation.
AB  - INTRODUCTION: Bursts of tachycardia arising in the pulmonary veins may play an
      important role in perpetuating atrial fibrillation (AF). However, the role of the
      coronary sinus (CS) in the perpetuation of AF has been unclear. The aim of this
      study was to determine whether the CS plays a role in perpetuation of AF. METHODS
      AND RESULTS: Pulmonary vein isolation was performed by segmental ostial ablation
      with radiofrequency energy in 22 consecutive patients with paroxysmal AF. Bipolar
      and unipolar electrograms recorded in the left atrium and CS were analyzed during
      atrial pacing from the mitral annulus and during AF. There was a mean of 2.5 +/-
      0.5 electrical connections between the CS and the left atrium. The electrical
      connections between the left atrium and CS were ablated with a mean of 6.2 +/-
      2.7 minutes of radiofrequency energy applied along the atrial side of the
      inferior mitral annulus. During AF, episodes of intermittent tachycardia
      alternated between the left atrium and the CS. Among the 22 patients, sustained
      AF was still inducible in 9 after pulmonary vein isolation. After electrical
      disconnection of the CS from the left atrium, sustained AF was inducible in only
      3 of these 9 patients. CONCLUSION: The CS may be a source of rapid repetitive
      electrical activity during AF. The lower probability of inducible sustained AF
      after electrical disconnection of the CS from the left atrium suggests that the
      CS may play a role in perpetuating AF.

PMID- 14678110
TI  - Spontaneous transition of 2:1 atrioventricular block to 1:1 atrioventricular
      conduction during atrioventricular nodal reentrant tachycardia: evidence
      supporting the intra-Hisian or infra-Hisian area as the site of block.
AB  - INTRODUCTION: The incidence of spontaneous transition of 2:1 AV block to 1:1 AV
      conduction during AV nodal reentrant tachycardia has not been well reported.
      Among previous studies, controversy also existed about the site of the 2:1 AV
      block during AV nodal reentrant tachycardia. METHODS AND RESULTS: In patients
      with 2:1 AV block during AV nodal reentrant tachycardia, the incidence of
      spontaneous transition of 2:1 AV block to 1:1 AV conduction and change of
      electrophysiologic properties during spontaneous transition were analyzed. Among
      the 20 patients with 2:1 AV block during AV nodal reentrant tachycardia, a His
      bundle potential was absent in blocked beats during 2:1 AV block in 8 patients,
      and the maximal amplitude of the His-bundle potential in the blocked beats was
      the same as that in the conducted beats in 4 patients and was significantly
      smaller than that in the conducted beats in 8 patients (0.49 +/- 0.25 mV vs 0.16
      +/- 0.07 mV, P = 0.007). Spontaneous transition of 2:1 AV block to 1:1 AV
      conduction occurred in 15 (75%) of 20 patients with 2:1 AV block during AV nodal
      reentrant tachycardia. Spontaneous transition of 2:1 AV block to 1:1 AV
      conduction was associated with transient right and/or left bundle branch block.
      The 1:1 AV conduction with transient bundle branch block was associated with
      significant His-ventricular (HV) interval prolongation (66 +/- 19 ms) compared
      with 2:1 AV block (44 +/- 6 ms, P < 0.01) and 1:1 AV conduction without bundle
      branch block (43 +/- 6 ms, P < 0.01). CONCLUSION: The 2:1 AV block during AV
      nodal reentrant tachycardia is functional; the level of block is demonstrated to
      be within or below the His bundle in a majority of patients with 2:1 AV block
      during AV nodal reentrant tachycardia, and a minority are possibly high in the
      junction between the AV node and His bundle.

PMID- 14678111
TI  - Role of compact node and posterior extension in direction-dependent changes in
      atrioventricular nodal function in rabbit.
AB  - INTRODUCTION: AV nodal conduction properties differ in the anterograde versus the
      retrograde direction. The underlying substrate remains unclear. We propose that
      direction-dependent changes in AV nodal function are the net result of those
      occurring in the slow and fast pathways. METHODS AND RESULTS: Anterograde and
      retrograde AV nodal properties were determined with a premature protocol before
      and after posterior extension (slow pathway) ablation, and before and after upper
      compact node (fast pathway) ablation. Each ablation was performed in a different
      group of six rabbit heart preparations. In control, nodal minimum conduction time
      (NCTmin) and effective refractory period (ERPN) typically were longer, and
      maximum conduction time (NCTmax) was shorter in the retrograde compared to the
      anterograde direction. Posterior extension ablation prolonged anterograde ERPN
      from 91 +/- 10 ms to 141 +/- 15 ms (P < 0.01) and shortened NCTmax from 150 +/-
      13 ms to 82 +/- 7 ms (P < 0.01) but did not affect retrograde conduction. Thus,
      the posterior extension normally contributes to the anterograde but not
      retrograde recovery curve. Compact node ablation prolonged anterograde conduction
      (NCTmin increased from 57 +/- 2 ms to 73 +/- 7 ms, P < 0.01) but did not alter
      ERPN and NCTmax. This ablation abolished retrograde conduction in two
      preparations and resulted in retrograde slow pathway conduction in four, the
      latter being interrupted by posterior extension ablation. Thus, the compact node
      accounts for the baseline of the recovery curve in both directions. Ablation of
      the compact node results in anterograde slow pathway conduction over the entire
      cycle length range and may result in retrograde slow pathway conduction.
      CONCLUSION: Direction-dependent properties of the AV node arise from those of the
      compact node-based fast pathway and posterior extension-based slow pathway.
      Normal AV node has bidirectional dual pathways.

PMID- 14678112
TI  - Effects of elevated extracellular potassium ion concentration on anodal
      excitation of cardiac tissue.
AB  - INTRODUCTION: Anodal excitation of cardiac tissue occurs by two mechanisms:
      "make" and "break." Anodal strength-interval curves are divided into two
      sections, with break excitation occurring at short intervals and make at long
      intervals. Our goal is to determine how an elevated extracellular potassium ion
      concentration, [K]o, affects the mechanism of anodal excitation and influences
      the anodal strength-interval curve. METHODS AND RESULTS: Computer simulations of
      unipolar stimulation were performed using the bidomain model, with membrane
      kinetics governed by the Luo-Rudy model. The diastolic threshold for anodal
      stimulation first decreased and then increased with increasing [K]o, reaching a
      minimum value at [K]o = 12 mM. The mechanism for diastolic anodal excitation was
      make for all [K]o values except 13.3 mM, in which case it was break. For low [K]o
      (4 and 8 mM) the break section of the anodal strength-interval contained a "dip,"
      but for high [K]o (12 and 13 mM), the dip disappeared. CONCLUSION: High [K]o
      predisposes cardiac tissue to break excitation, which is thought to play an
      important role in reentry induction and defibrillation. Because fibrillation
      raises extracellular [K]o levels, break excitation may play a more important role
      in defibrillation than is suggested by simulations and experiments using normal
      [K]o values.

PMID- 14678113
TI  - Atrioventricular nodal ablation and His-bundle pacing: an acute canine model for
      proarrhythmic risk assesment.
AB  - INTRODUCTION: QT interval prolongation following drug exposure is considered a
      marker for increased risk of drug-induced arrhythmias. QT interval measurements
      are common components of the safety pharmacology assessment of new therapeutic
      compounds but are potentially confounded by concurrent changes in heart rate that
      also alter QT intervals. We describe an anesthetized canine model of AV
      dissociation with His-bundle pacing that overcomes the confounding effects of a
      change in heart rate. METHODS AND RESULTS: Transvenous radiofrequency ablation of
      the AV node was performed in isoflurane-anesthetized dogs and followed by open
      chest implantation of bipolar pacing electrodes in the vicinity of the His
      bundle. Pace rates were adjusted from 50 to 190 in steps of 20 beats/min, holding
      each step for 30 seconds. At each paced rate, QT intervals were measured manually
      to the nearest 1 ms to construct paced QT interval-heart rate (QT-HR)
      relationships. Paired QT-HR relationships using identical ascending ramps of pace
      rates were compared to paired QT-HR relationships with an ascending and
      descending pace ramp to evaluate short-term reproducibility and hysteresis
      effects. For proof of concept, an additional QT-HR relationship was constructed
      in three dogs after intravenous administration of a compound known to alter QT
      intervals: one dog received terfenadine (0.48 mg/kg bolus followed by 0.017
      mg/kg/min infusion), one dog received quinidine (20 mg/kg), and the third dog
      received sotalol (1 and 3 mg/kg). Substantial inter-dog variation was found for
      QT-HR, although short-term reproducibility was high within one dog (average
      absolute difference for paired ascending ramps < 5 ms). QT intervals measured
      during descending paced ramps were generally lower than the value for the
      corresponding paced rate on an ascending ramp. This hysteretic effect was small,
      averaging < 7 ms over the entire ramp. All test compounds prolonged QT intervals
      and shifted the QT-HR relationship upward. Maximal QT prolongation was 30 ms for
      terfenadine, 50 ms for quinidine, and 59 ms for sotalol. CONCLUSION: AV nodal
      ablation and His-bundle pacing provide a sensitive animal model to identify acute
      effects of test compounds on indices of myocardial repolarization such as the QT
      interval. The model is devoid of confounding effects of changing heart rates
      while enabling identification of effects of drugs over a wide range of controlled
      rates.

PMID- 14678114
TI  - Magnetic electroanatomic mapping of an atrial tachycardia requiring ablation
      within the coronary sinus.
AB  - We describe a focal atrial tachycardia (AT) originating from the region of the
      inferoposterior mitral annulus in which ablation at the site of earliest
      endocardial activation during AT was unsuccessful. Three-dimensional
      electroanatomic mapping identified the earliest atrial activation within the
      coronary sinus. Radiofrequency energy delivered at this site within the CS
      terminated this tachycardia without any complications, suggesting an origin
      within the CS. To our knowledge, this is the first time a three-dimensional, high
      density activation map of such a tachycardia has been reported.

PMID- 14678115
TI  - Brief history of cardiac arrhythmias since the end of the nineteenth century:
      part I.

PMID- 14678116
TI  - Basic electrophysiology of the pulmonary veins and their role in atrial
      fibrillation: precipitators, perpetuators, and perplexers.

PMID- 14678117
TI  - Wide QRS Rhythm in a Young Woman with Recurrent Palpitations: what is the
      diagnosis?

PMID- 14678118
TI  - A Long RP' Interval Tachycardia: what is the mechanism?

PMID- 14678119
TI  - Acceleration of ventricular rate following atrial antitachycardia pacing: what is
      the mechanism?

PMID- 14678120
TI  - Three-dimensional computed tomography of the coronary venous system.

PMID- 14678121
TI  - Accessory pathway catheter ablation inside the neck of a coronary sinus
      diverticulum.

PMID- 14678123
TI  - Heart rate turbulance: an independant risk factor?

PMID- 14678124
TI  - Antiarrhythmic drugs: past, present and future.

PMID- 14678125
TI  - Location of mutation in the KCNQ1 and phenotypic presentation of long QT
      syndrome.
AB  - INTRODUCTION: Recent data showed that long QT syndrome (LQTS) patients with
      mutations in the pore region of the HERG (LQT2) gene have significantly higher
      risk of cardiac events than subjects with mutations in the non-pore region. The
      aim of this study was to determine whether there is an association between the
      location of mutations in the KCNQ1 gene and cardiac events in LQT1 patients.
      METHODS AND RESULTS: The study population consisted of 294 LQT1 patients with
      KCNQ1 gene mutations. Demographic, clinical, and follow-up information was
      compared among subjects with different locations of KCNQ1 mutations defined as
      pre-pore region including N-terminus (1-278), pore region (279-354), and post
      pore region including C-terminus (>354). Cardiac events observed during follow-up
      from birth until age of last contact or age 40 years were defined as syncope,
      cardiac arrest, or sudden death. There were 164 (56%) LQT1 patients with pre-pore
      mutations, 101 (34%) with pore mutations, and 29 (10%) with post-pore mutations.
      QTc duration did not differ significantly among the three subgroups (mean QTc =
      494, 487, and 501 ms, respectively). There was no significant difference between
      groups with regard to the risk of cardiac events by age 40 years. CONCLUSION:
      There are no significant differences in clinical presentation, ECG parameters,
      and cardiac events among LQT1 patients with different locations of KCNQ1
      mutations. These findings indicate that factors other than location of mutation
      influence clinical phenotype in patients with LQT1 mutations.

PMID- 14678126
TI  - Deciphering the message of long QT genotypes.

PMID- 14678127
TI  - Incidence and characteristics of type-2 breaks in response to antitachycardia
      pacing therapy in implantable cardioverter defibrillator patients.
AB  - INTRODUCTION: Antitachycardia pacing (ATP) effectively treats monomorphic
      ventricular tachycardia (VT). The VT may cease immediately upon ATP completion
      (type-1 break), or it may persist or change to another tachyarrhythmia for one or
      more beats before termination (type-2 break). We investigated the prevalence and
      characteristics of type-2 breaks in ICD patients. METHODS AND RESULTS: We
      analyzed VT episodes with stored electrograms that had at least one ATP therapy
      delivered in PainFREE Rx trial, a multicenter trial with 220 coronary artery
      disease patients. Further subanalysis was performed by classifying the VT as slow
      or fast based on the cycle length (CL); slow VT: CL >320 ms, fast VT: 240 < or
      =CL < or =320 ms. To assess the effect of ATP on VT, comparison was performed of
      pre-ATP and post-ATP CL variability, average CL, and morphology. A total of 514
      episodes (264 slow VT and 250 fast VT) were analyzed. The burst ATP terminated
      457 (89%; 239 slow VT and 218 fast VT) of 514 episodes. Forty five (10%) episodes
      in 18 (32%) patients had type-2 breaks. The mean number of beats during type-2
      breaks was 5.4 +/- 3.1 (median 4). The mean time for episode termination measured
      from the end of ATP to return of first sinus/paced beat was 2.9 +/- 1.2 seconds
      (median 2.6). The VT CL variability increased by 150% after ATP delivery. The ATP
      affected either VT CL or morphology, or both of 36 (80%) type-2 breaks (9%
      accelerated, 47% decelerated, 22% changed in morphology only). Among the 9 (20%)
      episodes that remained unchanged in morphology and CL, four episodes (9%) were
      unaffected by ATP. CONCLUSION: Approximately 10% of VT episodes that were
      successfully terminated with burst ATP therapy had type-2 breaks. Type-2 breaks
      are associated with an increase in CL variability. Approximately 9% of all type-2
      episodes may be spontaneously terminating nonsustained VT given that ATP did not
      affect these episodes in any way.

PMID- 14678128
TI  - Randomized controlled trial of fixed rate versus rate responsive pacing after
      radiofrequency atrioventricular junction ablation: quality of life, ventricular
      refractoriness, and paced QT dispersion.
AB  - INTRODUCTION: Ablation of the AV junction is a widely accepted treatment of drug
      refractory atrial fibrillation. Long-term pacing of the right ventricular (RV)
      apex following AV junction ablation can result in adverse cardiac remodeling.
      However, anecdotal studies report that pacing too slowly following AV junction
      ablation was associated with propensity to sudden cardiac death. The aim of this
      study was to provide information about the balance between measures of quality of
      life versus measures of electrical remodeling achieved by pacing with different
      rate modalities in a randomized pilot clinical trial. METHODS AND RESULTS:
      Patients with permanent atrial fibrillation were randomized to VVI (80 beats/min)
      versus VVIR (minimum rate 80 beats/min), whereas patients with paroxysmal atrial
      fibrillation were randomized to DDI versus DDDR pacing at discharge from
      hospital. Serially, measurements of exercise capacity, quality of life, cycle
      length dependence of QT dispersion (QTdisp), RV refractoriness, and the incidence
      of nonsustained ventricular tachycardia were made in 28 patients over a 6-month
      follow-up period. Time-dependent increases in QTdisp were observed in patients
      randomized to the rate responsive mode (RR-ON) but only when paced at 40
      beats/min. This was paralleled by time-dependent increases in RV refractoriness
      (270 +/- 11 ms at baseline to 302 +/- 5 ms at 6 months) in patients with RR-ON.
      RR-ON also was associated with trends to an increasing incidence of episodes of
      nonsustained ventricular tachycardia and worsening of some measures of quality of
      life. Exercise capacity was not substantially different in the randomized groups.
      CONCLUSION: Rate responsive pacing results in electrical remodeling of the
      ventricle following AV junction ablation, but exercise capacity was similar in
      groups with RR-ON or RR-OFF.

PMID- 14678129
TI  - More is not always better.

PMID- 14678130
TI  - Dissociated pulmonary vein arrhythmia: incidence and characteristics.
AB  - INTRODUCTION: The incidence and characteristics of dissociated arrhythmia
      confined to the pulmonary vein (PV) following disconnection have not been
      described in a large number of patients with paroxysmal atrial fibrillation.
      METHODS AND RESULTS: This was a prospective study of 152 patients (29 female,
      mean age 51 +/- 11 years) referred for catheter ablation of drug-refractory
      paroxysmal atrial fibrillation. Following ostial ablation, the rate and
      regularity of any dissociated venous activity was analyzed with and without
      isoproterenol infusion (to achieve a heart rate of 120-140 beats/min). Patients
      then were classified according to their venous dissociated activity. Group 1
      consisted of patients in whom the dissociated PV spike had a slow rhythm >1,200
      ms. Group 2 consisted of patients with spontaneous repetitive dissociated
      discharges confined in the vein with a cycle length <400 ms. A total of 384 PVs
      were ablated in 152 patients. Disappearance of all venous potentials was observed
      in 88% of the treated veins; at least one dissociated venous potential was
      observed in the remaining 12%. Group 1 activity was seen more often than group 2
      (23 patients, mean cycle length 2,300 +/- 1,100 ms vs 13 patients, mean cycle
      length 179 +/- 77 ms). Dissociated PV arrhythmia was seen most often in the right
      superior PV (19%). CONCLUSION: Dissociation as the endpoint of PV disconnection
      was observed in 12% of PVs. Due to the capricious nature of this activity, the
      actual incidence is almost certainly higher. The dissociated venous rhythm
      usually is slow and, less commonly, is rapid and repetitive.

PMID- 14678131
TI  - Right ventricular outflow versus apical pacing in pacemaker patients with
      congestive heart failure and atrial fibrillation.
AB  - INTRODUCTION: Prior studies suggest that right ventricular apical (RVA) pacing
      has deleterious effects. Whether the right ventricular outflow tract (RVOT) is a
      more optimal site for permanent pacing in patients with congestive heart failure
      (CHF) has not been established. METHODS AND RESULTS: We conducted a randomized,
      cross-over trial to determine whether quality of life (QOL) is better after 3
      months of RVOT than RVA pacing in 103 pacemaker recipients with CHF, left
      ventricular (LV) systolic dysfunction (LV ejection fraction < or = 40%), and
      chronic atrial fibrillation (AF). An additional aim was to compare dual-site
      (RVOT + RVA, 31-ms delay) with single-site RVA and RVOT pacing. QRS duration was
      shorter during RVOT (167 +/- 45 ms) and dual-site (149 +/- 19 ms) than RVA pacing
      (180 +/- 58 ms, P < 0.0001). At 6 months, the RVOT group had higher (P = 0.01)
      role-emotional QOL subscale scores than the RVA group. At 9 months, there were no
      significant differences in QOL scores between RVOT and RVA groups. Comparing RVOT
      to RVA pacing within the same patient, mental health subscale scores were better
      (P = 0.03) during RVOT pacing. After 9 months of follow-up, LVEF was higher (P =
      0.04) in those assigned to RVA rather than RVOT pacing between months 6 and 9.
      After 3 months of dual-site RV pacing, physical functioning was worse (P = 0.04)
      than during RVA pacing, mental health was worse (P = 0.02) than during RVOT
      pacing, and New York Heart Association (NYHA) functional class was slightly
      better (P = 0.03) than during RVOT pacing. There were no other significant
      differences between RVA, RVOT and dual-site RV pacing in QOL scores, NYHA class,
      distance walked in 6 minutes, LV ejection fraction, or mitral regurgitation.
      CONCLUSION: In patients with CHF, LV dysfunction, and chronic AF, RVOT and dual
      site RV pacing shorten QRS duration but after 3 months do not consistently
      improve QOL or other clinical outcomes compared with RVA pacing.

PMID- 14678132
TI  - Ventricular-based pacing: one site fits all?

PMID- 14678133
TI  - Combined efficacy of atrial septal lead placement and atrial pacing algorithms
      for prevention of paroxysmal atrial tachyarrhythmia.
AB  - INTRODUCTION: The combined role of atrial septal lead location and atrial pacing
      algorithms in the prevention of atrial tachyarrhythmias (AT/AF), including both
      atrial fibrillation and flutter, is unknown. We tested the hypothesis that atrial
      prevention pacing algorithms could decrease AT/AF frequency in patients with
      atrial septal leads, bradycardia, and paroxysmal AT/AF. METHODS AND RESULTS: A
      total of 298 patients (age 70 +/- 10 years; 61% male) from 35 centers were
      implanted with a DDDRP pacing system including three AT/AF prevention pacing
      algorithms. Lead site was randomized at implant to right atrial septal or
      nonseptal. Patients were randomized 1 month postimplant to AT/AF prevention ON or
      OFF for 3 months and then crossed over for 3 months. Patients logged symptomatic
      AT/AF episodes via a manual activator. Prevention efficacy was evaluated based on
      intention-to-treat in 277 patients (138 septal) with complete follow-up. No
      changes in device-recorded AT/AF frequency or burden were observed with
      algorithms OFF versus ON or between patients randomized to septal versus
      nonseptal lead location. Analysis of other secondary outcomes revealed that AT/AF
      prevention pacing resulted in decreased atrial premature contractions in both the
      septal (1.9 [0.2-8.7] vs 3.3 [0.3-10.6]x 103/day; P < 0.01) and nonseptal groups
      (0.9 [0.2-3.3] vs 1.3 [0.3-5.5]x 103/day; P < 0.001). Patients with septal leads
      had fewer symptomatic AT/AF episodes ON versus OFF (1.4 +/- 3.0 vs 2.5 +/-
      5.2/month, P = 0.01). CONCLUSION: The combination of three atrial prevention
      pacing algorithms did not decrease device classified atrial tachyarrhythmia
      frequency or burden during a 3-month cross-over period in bradycardic patients
      and septal or nonseptal atrial pacing leads. Prevention pacing was associated
      with decreased frequency of premature atrial contractions and with decreased
      symptomatic atrial tachyarrhythmia frequency in patients with atrial septal
      leads.

PMID- 14678134
TI  - Development of an optrode for intramural multisite optical recordings of Vm in
      the heart.
AB  - INTRODUCTION: Optical mapping of transmembrane potential (Vm) is an important
      tool in the investigation of impulse propagation in the heart. It provides
      valuable information about spatiotemporal changes of Vm that cannot be obtained
      by other techniques, but it presently is limited to measurements from the heart
      surfaces. Therefore, the goal of this work was to develop a technique for
      intramural multisite optical measurements of Vm using fiberoptic technology.
      METHODS AND RESULTS: An optrode, a bundle of thin optical fibers, was developed
      for measuring intramural optical signals at multiple sites in the heart. The
      optrode consisted of seven fibers with diameter of 225 microm arranged in a
      hexagonal pattern that were used to deliver excitation light to the myocardium,
      to collect the emitted fluorescence, and to project the light onto a 16 x 16
      array of photodiode detectors. Rabbit hearts were stained with the Vm-sensitive
      dye RH-237. Fluorescence was excited using a 100-W Hg lamp. Intramural action
      potentials were recorded at multiple sites separated by 2 mm inside the left
      ventricle. Signal-to-noise (RMS) ratio was 21.2 +/- 12 (n = 7) without averaging
      or ratiometry and with negligible cross-talk (<1.9%) between the neighboring
      photodiodes. The size of the recording area for an individual fiber was estimated
      at approximately 0.8 mm. CONCLUSION: These data demonstrate feasibility of
      multisite transmural measurements of Vm without signal averaging and ratiometry.
      This technique might become useful in studies of transmural impulse conduction
      during arrhythmias and defibrillation.

PMID- 14678135
TI  - From the needle to the optrode: assessment of cardiac intramural electrical
      activity.

PMID- 14678136
TI  - Up-regulation of connexin45 in heart failure.
AB  - INTRODUCTION: Heart failure is associated with reduced expression of the major
      gap junction protein connexin43 (Cx43), which may contribute to arrhythmias and
      sudden cardiac death in this patient population. Other cardiac connexins may be
      altered as well. Because connexin45 (Cx45) has been shown to colocalize with
      Cx43, we determined whether the number, size, or distribution of Cx45 gap
      junctions is altered in the failing heart. METHODS AND RESULTS: Cx45 expression
      levels were measured by immunoblotting and quantitative immunostaining in failing
      and control human left ventricles. Total Cx45 protein was significantly (P =
      0.021) up-regulated 1.8-fold in failing hearts. Cx45 immunohistochemical signal
      was increased by 80% (P = 0.005) due to a 3.5-fold increase in the number of gap
      junctions containing Cx45. Cx45 mRNA was not altered in failing hearts,
      suggesting reduced degradation of Cx45 protein in the failing heart. Cx43 signal,
      on the other hand, was reduced by 49% in failing hearts. Double-label experiments
      demonstrated colocalization of Cx45 and Cx43 in the same gap junctions.
      CONCLUSION: Cx45 is markedly enhanced in the failing heart. Up-regulation of Cx45
      in conjunction with down-regulation of Cx43 could result in abnormal impulse
      propagation and generation of ventricular arrhythmias, thereby predisposing
      patients in heart failure to sudden cardiac death.

PMID- 14678137
TI  - Gap junction remodeling in the failing heart: different connexins--different
      message?

PMID- 14678138
TI  - Optical mapping of transmural activation induced by electrical shocks in isolated
      left ventricular wall wedge preparations.
AB  - INTRODUCTION: It is believed that electrical shocks interrupt fibrillation by
      directly stimulating the bulk of ventricular myocardium in excitable states, but
      how shocks activate intramural tissue layers is not known. In this study, Vm
      responses and transmural activation patterns induced by shocks during diastole
      were measured in isolated coronary perfused preparations of porcine left
      ventricle. METHODS AND RESULTS: Rectangular shocks (duration = 10 ms; field
      strength, E = 1-44 V/cm) were applied across preparations (thickness = 14.9 +/-
      2.5 mm, n = 9) via large mesh electrodes during diastole or action potential (AP)
      plateau. Vm responses at the transmural surface were measured using optical
      mapping technique (resolution = 1.2 mm). Depending on shock strength, three types
      of Vm responses were observed. (1) Weak shocks (E approximately 1-4 V/cm) applied
      in diastole induced APs with simple monophasic upstrokes. The latency and time of
      transmural activation (TTA) rapidly decreased with increasing shock strength.
      Earliest activation occurred predominantly at the cathodal side of preparations
      in the areas that exhibited maximal DeltaVm during AP plateau. (2) Intermediate
      shocks (E approximately 4-23 V/cm) induced monophasic and biphasic upstrokes that
      were paralleled with predominantly negative plateau DeltaVm. Activation was
      initiated at multiple transmural sites and rapidly spread across the myocardial
      wall (TTA = 0.6 +/- 0.2 ms). (3) Very strong shocks (E approximately 23-44 V/cm)
      could cause triphasic upstrokes, likely reflecting occurrence of membrane
      electroporation, and delayed activation (TTA = 6.7 +/- 3.8 ms) at sites of
      largest negative plateau DeltaVm. CONCLUSION: Shocks applied during diastole
      cause direct and rapid (within 1 ms) activation of ventricular bulk over a wide
      range of shock strengths, supporting the excitatory hypothesis of defibrillation.
      Very strong shocks can cause multiphasic Vm responses and delayed activation.

PMID- 14678139
TI  - Diastolic shocking experience: do virtual electrodes exist only during systole?

PMID- 14678140
TI  - Model for the onset of fibrillation following coronary artery occlusion.
AB  - INTRODUCTION: It is the hypothesis of this article that the onset of fibrillation
      following a coronary artery occlusion is a direct consequence of the spatial
      inhomogeneity of chemical processes that occur following the occlusion. In
      particular, the localized increase of extracellular potassium and decrease of ATP
      availability lead to an increase of resting potential in the affected cells. This
      difference in potential between affected cells and normal cells drives a current,
      the "current of injury," which may drive oscillations in the border zone, a
      "border zone arrhythmia." The border zone arrhythmia may drive a "breakup
      instability" (related to the action potential duration restitution instability)
      in the surrounding tissue, leading to self-sustained fibrillation. METHODS AND
      RESULTS: In this article, we present a mathematical model demonstrating this
      transition from normal to fibrillatory dynamics, describing the general
      conditions under which this transition occurs and showing in a simple ionic model
      the way in which spatial inhomogeneity alone can initiate self-sustained
      reentrant activity. CONCLUSION: Using general arguments and numerical simulations
      with generic models of excitable media, we have demonstrated that a spatial
      region with an elevated resting potential surrounded by a spatial region wherein
      action potentials are foreshortened can drive a breakup instability, leading to
      the rapid initiation of a fibrillatory state.

PMID- 14678141
TI  - Beta receptor blockade potentiates the antiarrhythmic actions of d-sotalol on
      reentrant ventricular tachycardia in a canine model of myocardial infarction.
AB  - INTRODUCTION: The importance of beta receptor blockade for the antiarrhythmic
      action of sotalol has not been completely elucidated. We determined how beta
      receptor blockade interacts with the effects of potassium channel blockade on
      reentrant circuits. METHODS AND RESULTS: Sustained ventricular tachycardia was
      induced by programmed stimulation in dogs 4 days after left anterior coronary
      artery occlusion and reentrant circuits in the epicardial border zone (EBZ)
      mapped. The effects of the beta receptor-blocking drug, esmolol, the potassium
      channel-blocking drug d-sotalol, which lacks beta receptor-blocking effects, and
      the combination of the two drugs on the reentrant circuits that cause tachycardia
      were determined. Esmolol did not alter the ability to induce tachycardia. Small
      changes in the location or extent of lines of block in reentrant circuits
      accounted for small decreases or increases in tachycardia cycle lengths. d
      Sotalol prolonged the lines of block in reentrant circuits, slowed propagation
      around the circuits, and prolonged tachycardia cycle length, but it did not stop
      tachycardia or prevent the induction of tachycardia. The combination of esmolol
      and d-sotalol prevented the initiation of sustained tachycardia. The stimulated
      premature impulse either blocked before reentering or traversed the circuit
      several times prior to blocking in a region of fractionated electrograms. The
      addition of esmolol to d-sotalol abolished the reverse use-dependent effects of d
      sotalol alone on effective refractory period (ERP) and significantly prolonged
      ERP in the area of the reentrant circuit. CONCLUSION: Beta receptor blockade is
      important for the antiarrhythmic effects of d,l-sotalol on reentrant ventricular
      tachycardia in this model. The mechanism is speculative but may involve
      potentiation of d-sotalol actions to prolong ERP or effects on gap junctions.

PMID- 14678143
TI  - Atrial fibrillation: mechanistic insights from biatrial (and triatrial) mapping.
AB  - Percutaneous radiofrequency ablation of pulmonary vein potentials has been shown
      to eliminate atrial fibrillation in a subset of patients characterized by
      frequent and repetitive paroxysms of atrial fibrillation. However, pulmonary vein
      disconnection has had only limited success at curing patients with persistent
      atrial fibrillation. In those patients, left atrial substrate modification and
      linear ablation strategies have had substantially higher success rates.
      Furthermore, in other patients, elimination of right atrial triggers (superior
      vena cava) or modification of right atrial substrate has been required for
      elimination of atrial fibrillation. Finally, the realization that the coronary
      sinus is a third atrial chamber that can both initiate and maintain atrial
      fibrillation has provided new understanding to the pathogenesis of atrial
      fibrillation. From a clinical perspective, only careful anatomic and mapping
      strategies specifically aimed at each subset of patients with atrial fibrillation
      will allow for pattern recognition and establish which mechanisms are responsible
      for initiation and maintenance of atrial fibrillation. Only the latter will allow
      for increased long-term success rates of ablation of atrial fibrillation.

PMID- 14678142
TI  - Increase in ventricular tachycardia frequency after biventricular implantable
      cardioverter defibrillator upgrade.
AB  - We report the case of a patient in whom transvenous left ventricular pacing lead
      placement at the time of a biventricular upgrade led to an exacerbation of
      clinical monomorphic ventricular tachycardia (MVT). At implant, slow left
      ventricular pacing repeatedly induced sustained MVT. However, testing of the
      biventricular pacing showed no MVT inducibility, and the system was implanted.
      The patient was readmitted due to multiple episodes of the MVT observed at
      implant. The MVT was controlled with pharmacotherapy, allowing the patient to
      continue with biventricular pacing.

PMID- 14678144
TI  - 4:2 atrioventricular block: what is the mechanism?

PMID- 14678145
TI  - Marshall bundle and the valve of Vieussens.

PMID- 14678146
TI  - Visualization of pulmonary vein ice ball by intracardiac echocardiography during
      catheter cryoablation.

PMID- 14678148
TI  - Pathophysiology of Brugada syndrome.

PMID- 14678150
TI  - Molecular genetics of arrhythmias and cardiovascular conditions associated with
      arrhythmias.

PMID- 14678154
TI  - Serodiagnosis of infectious diseases with antigen microarrays.
AB  - AIMS: To generate protein microarrays by printing microbial antigens on slides to
      enable the simultaneous determination in human sera of antibodies directed
      against Toxoplasma gondii, rubella virus, cytomegalovirus and herpes simplex
      virus (HSV) types 1 and 2. METHODS AND RESULTS: Antigens were printed on
      activated glass slides using high-speed robotics. The slides were incubated with
      serum samples and subsequently with fluorescently labelled secondary antibodies.
      Human IgG and IgM bound to the printed antigens were detected using confocal
      scanning microscopy and quantified with internal calibration curves. The
      microarray assay could detect as little as 0.5 pg of both IgG and IgM bound onto
      the glass surface. Precision profiles ranged from 1.7 to 18.5% for all the
      antigens. Microarrays and commercial ELISAs were utilized to detect serum
      antibodies against the ToRCH antigens in a panel of characterized human sera.
      Overall >80% concordance was obtained between microarray and ELISA kits in the
      classification of sera. CONCLUSIONS: These results indicate that the microarray
      is a suitable assay format for the serodiagnosis of infectious diseases.
      SIGNIFICANCE AND IMPACT OF STUDY: Antigen microarrays can be optimized for
      clinical use, their performance is equivalent to ELISA but they offer significant
      advantages in throughput, convenience and cost.

PMID- 14678155
TI  - Molecular signatures for diagnosis of infection: application of microarray
      technology.
AB  - Technological developments such as microarray-based DNA, RNA and protein
      detection have opened new fields in genomics and proteomics. This review aims to
      highlight the potential value and limitation of this methodology to design and
      extract signature-based diagnostic markers for infectious disease.

PMID- 14678156
TI  - Analysis of parasites by electrorotation.
AB  - AIMS: The application of the AC electrokinetic technique of electrorotation for
      studying eukaryotic parasite transmission stages is reviewed. Electrorotation is
      a noninvasive technique that utilizes electrically energized microelectrode
      structures within micro-fluidic chambers to probe the physiological structure of
      micro-organisms. Application of the technique to the transmission life cycle
      stages of three separate genera of protozoan parasites, Cryptosporidium, Giardia
      and Cyclospora, and one nematode genus Ascaris, each of significant public health
      importance, is described. METHODS AND RESULTS: Standard electrorotation
      apparatus, consisting of micro-fabricated electrodes in a fluidic chip,
      quadrature sinusoidal signal generator, microscope and image capture system, was
      used to study each organism. Spectra of cellular rotation rate were recorded as a
      function of applied electric field frequency and compared with standardized
      biological tests, where appropriate, to illustrate the effectiveness and
      versatility of the electrorotation technique. CONCLUSIONS: Electrorotational
      determination of the viability of individual G. intestinalis cysts,
      Cryptosporidium parvum and Cyclospora cayetanensis oocysts has been achieved. The
      sporulation state of Cyclospora cayetanensis oocysts was also readily determined,
      as was the fertilization state of A. suum ova. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Electrorotation is a simple, noninvasive and versatile analytical
      technique suited to a wide range of particle types and capable of incorporation
      into integrated Lab-on-a-chip devices.

PMID- 14678157
TI  - Bioluminescent bioreporter integrated circuits: potentially small, rugged and
      inexpensive whole-cell biosensors for remote environmental monitoring.

PMID- 14678158
TI  - Fluorescence-based array biosensors for detection of biohazards.

PMID- 14678159
TI  - Species differentiation and antibiotic susceptibility testing with DNA
      microarrays.

PMID- 14678160
TI  - Suppression of Rhizoctonia solani diseases of sugar beet by antagonistic and
      plant growth-promoting yeasts.
AB  - AIMS: Isolates of Candida valida, Rhodotorula glutinis and Trichosporon asahii
      from the rhizosphere of sugar beet in Egypt were examined for their ability to
      colonize roots, to promote plant growth and to protect sugar beet from
      Rhizoctonia solani AG-2-2 diseases, under glasshouse conditions. METHODS AND
      RESULTS: Root colonization abilities of the three yeast species were tested using
      the root colonization plate assay and the sand-tube method. In the root
      colonization plate assay, C. valida and T. asahii colonized 95% of roots after 6
      days, whilst Rhod. glutinis colonized 90% of roots after 8 days. Root
      colonization abilities of the three yeast species tested by the sand-tube method
      showed that roots and soils attached to roots of sugar beet seedlings were
      colonized to different degrees. Population densities showed that the three yeast
      species were found at all depths of the rhizosphere soil adhering to taproots up
      to 10 cm, but population densities were significantly (P < 0.05) greater in the
      first 4 cm of the root system compared with other root depths. The three yeast
      species, applied individually or in combination, significantly (P < 0.05)
      promoted plant growth and reduced damping off, crown and root rots of sugar beet
      in glasshouse trials. The combination of the three yeasts (which were not
      inhibitory to each other) resulted in significantly (P < 0.05) better biocontrol
      of diseases and plant growth promotion than plants exposed to individual species.
      CONCLUSIONS: Isolates of C. valida, Rhod. glutinis and T. asahii were capable of
      colonizing sugar beet roots, promoting growth of sugar beet and protecting the
      seedlings and mature plants from R. solani diseases. This is the first successful
      attempt to use yeasts as biocontrol agents against R. solani which causes root
      diseases. SIGNIFICANCE AND IMPACT OF THE STUDY: Yeasts were shown to provide
      significant protection to sugar beet roots against R. solani, a serious soil
      borne root pathogen. Yeasts also have the potential to be used as biological
      fertilizers.

PMID- 14678161
TI  - Effect of wine yeast monoculture practice on the biodiversity of non
      Saccharomyces yeasts.
AB  - AIMS: The objective of this work was to study the effect of the use of
      Saccharomyces cerevisiae monocultures over the biodiversity of non-Saccharomyces
      yeasts in wine-producing areas in Chile. METHODS AND RESULTS: Microvinifications
      were carried out with grape musts of two areas. In one of them, the fermentation
      is carried out mainly in a spontaneous manner, whereas in the other the musts are
      inoculated with commercial yeasts. The isolated yeasts were identified by the
      internal transcribed (ITS)/restriction fragment length polymorphism technique. In
      the industrial production area less variability of yeast genera was observed as
      compared with the traditional area, an observation that is greatest at the end of
      the fermentation. Furthermore, a study of the production of extracellular enzymes
      was done. The majority of the yeasts showed at least one of the activities
      assayed with the exception of beta-glycosidase. CONCLUSION: The results suggest
      that in the industrialized area the diversity of yeasts is less in the
      traditional area. Likewise, the potentiality of the non-Saccharomyces yeasts as
      enzyme producers with industrial interest has been confirmed. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study shows the negative effect of the use of
      monocultures over the biodiversity of yeasts in wine-producing regions.

PMID- 14678162
TI  - Screening and typing of Patagonian wine yeasts for glycosidase activities.
AB  - AIMS: The purpose of this study was to select autochthonous glycosidase producer
      yeasts with potential use in industrial production of Patagonian red wines.
      METHODS AND RESULTS: The study was carried out in oenological autochthonous
      yeasts from Comahue region (Argentinean North Patagonia). A set of screenable
      yeast phenotypic characteristics indicative of their potential usefulness in more
      aromatic red wine production was defined and tested in both, Saccharomyces and
      non-Saccharomyces populations. Twelve isolates showing six different glycosidase
      phenotypes were selected and they were characterized at species and strain levels
      using molecular methods. A close correlation between molecular and phenotypic
      characteristics was observed. Five strains belonging to Candida guilliermondii,
      C. pulcherrima and Kloeckera apiculata with highest constitutive beta-glucosidase
      activity levels without anthocyanase activity were discriminated. Some of them
      also showed constitutive beta-xylosidase and inductive alpha-rhamnosidase
      activities. CONCLUSIONS: The extension of the selection of oenological yeast to
      non-Saccharomyces species provided strains possessing novel and interesting
      oenological characteristics which could have significant implications in the
      production of more aromatic young red wine. SIGNIFICANCE AND IMPACT OF THE STUDY:
      As these non-Saccharomyces are indigenous to wine, they can be used in mixed
      starters at the beginning or as pure cultures at the end fermentation to
      contribute in enhancing the wine nuance that is typical of this specific area.

PMID- 14678163
TI  - Modelling and predicting the simultaneous growth of Listeria monocytogenes and
      spoilage micro-organisms in cold-smoked salmon.
AB  - AIMS: To evaluate and model the simultaneous growth of Listeria monocytogenes and
      spoilage micro-organisms in cold-smoked salmon. METHODS AND RESULTS: Growth
      kinetics of L. monocytogenes, lactic acid bacteria (LAB), Enterobacteriaceae,
      enterococci and Photobacterium phosphoreum were determined in two series of
      challenge tests with sliced and vacuum-packed cold-smoked salmon (SVP-CSS). The
      product contained a high level of smoke components and at 2 degrees C levels of
      L. monocytogenes increased <100-fold in 193 days. Without the addition of
      spoilage micro-organisms, L. monocytogenes reached ca 108 CFU g-1 at 5, 10, 17.5
      and 25 degrees C. Inoculation with spoilage micro-organisms reduced this level to
      102-104 CFU g-1. LAB dominated the spoilage microfora of SVP-CSS and competition
      between LAB and L. monocytogenes in SVP-CSS was appropriately described by a
      simple expansion of the Logistic model. This interaction model aided in
      predicting the growth of L. monocytogenes in naturally contaminated SVP-CSS when
      it was used in combination with expanded versions of existing secondary models
      for L. monocytogenes and LAB. CONCLUSIONS: Temperature, water activity/NaCl,
      simultaneous growth of LAB, smoke components and to a lesser extent lactate and
      pH control growth of L. monocytogenes in SVP-CSS. These factors must be included
      in mathematical models to predict growth of the pathogen in this product.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The suggested predictive model can be used
      to support assessment and management of the human health risk due to L.
      monocytogenes in SVP-CSS.

PMID- 14678164
TI  - Evaluation of the effect of cleaning regimes on biofilms of thermophilic bacilli
      on stainless steel.
AB  - AIMS: To determine the mechanism for both the removal and inactivation of 18-h
      biofilms of a thermophilic Bacillus species that optimally grows at 55 degrees C
      on stainless steel. METHODS AND RESULTS: The cleaning strategies tested were
      based on biofilm biochemistry and physiology, and focused on the chemistry of the
      cleaners, the duration and temperature of the cleaning process and a combination
      of various cleaners. The success of the cleaning regimes was determined based on
      the removal of cells and organic debris and the elimination of viable cells. The
      results confirmed that a caustic (75 degrees C for 30 min) and acid (75 degrees C
      for 30 min) wash, relied upon heavily in most food processing industries for
      cleaning-in-place systems, was successful in removing these biofilms. However,
      any changes in the concentrations of these cleaners or the temperature of
      cleaning drastically affected the overall outcome. Alternative cleaning agents
      based on enzymatic or nonenzymatic breakdown of cellular proteins or
      polysaccharides, surfactant action, use of oxidative attack and free radicals
      varied in degrees of their success. Combining proteolytic action with surfactants
      increased wetability and therefore enhanced the cleaning efficiency. CONCLUSIONS:
      Several procedures, including caustic/acid and enzyme based cleaners, will be
      satisfactory, provided that the correct process parameters are observed i.e.
      concentration, time, temperature and kinetic energy (flow). Confirmation of these
      results should be carried out in a pilot plant through several use/clean cycles.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Confidence in standard and alternative
      cleaning procedures for food manufacturing plant to prevent contamination with
      thermophilic bacilli that threaten product quality.

PMID- 14678165
TI  - Phylogenetic analysis and in situ identification of the intestinal microbial
      community of rainbow trout (Oncorhynchus mykiss, Walbaum).
AB  - AIMS: To identify the dominant culturable and nonculturable microbiota of rainbow
      trout intestine. METHODS AND RESULTS: Microbial density of rainbow trout
      intestine was estimated by direct microscopic counts (4',6-diamidino-2
      phenylindole, DAPI) and by culturing on tryptone soya agar (TSA). Differential
      gradient gel electrophoresis analysis of bacterial DNA from intestinal samples,
      re-amplification of bands and sequence analysis was used to identify the bacteria
      that dominated samples where aerobic counts were < or =2% of the DAPI counts. 16S
      rDNA gene sequences of 146 bacterial isolates and three sequences of uncultured
      bacteria were identified. A set of oligonucleotide probes was constructed and
      used to detect and enumerate the bacterial community structure of the
      gastrointestinal tract of rainbow trout by fluorescence in situ hybridization
      (FISH). Members of the gamma subclass of Proteobacteria (mainly Aeromonas and
      Enterobacteriaceae) dominated the bacterial population structure. Acinetobacter,
      Pseudomonas, Shewanella, Plesiomonas and Proteus were also identified together
      with isolates belonging to the beta subclass of Proteobacteria and Gram-positive
      bacteria with high and low DNA G + C content. In most samples, the aerobic count
      (on TSA) was 50-90% of the direct (DAPI) count. A bacterium representing a
      previously unknown phylogenetic lineage with only 89% 16S rRNA gene sequence
      similarity to Anaerofilum pentosovorans was detected in intestinal samples where
      aerobic counts were < or =2% of direct (DAPI) counts. Ten to 75% of the microbial
      population in samples with low aerobic counts hybridized (FISH) with a probe
      constructed against this not-yet cultured bacterium. CONCLUSIONS: Proteobacteria
      belonging to the gamma subclass dominated the intestinal microbiota of rainbow
      trout. However, in some samples the microflora was dominated by uncultivated,
      presumed anaerobic, micro-organisms. The bacterial population structure of
      rainbow trout intestine, as well as total bacterial counts, varied from fish to
      fish. SIGNIFICANCE AND IMPACT OF THE STUDY: Good correlation was seen between
      cultivation results and in situ analysis, however, a molecular approach was
      crucial for the identification of organisms uncultivated on TSA.

PMID- 14678166
TI  - The contribution of bacteriocin to inhibition of Listeria monocytogenes by
      Carnobacterium piscicola strains in cold-smoked salmon systems.
AB  - AIMS: To study the importance of bacteriocin production for the antilisterial
      effect of a bacteriocinogenic Carnobacterium piscicola strain A9b on growth of
      Listeria monocytogenes in broth and cold-smoked salmon systems. METHODS AND
      RESULTS: Acriflavin treatment of strain A9b resulted in loss of bacteriocin
      production and of immunity to carnobacteriocin B2. Two plasmids present in the
      wild-type were lost in the variant that was also more sensitive to bavaricin and
      leucocin A than the wild-type indicating cross-resistance to class IIa
      bacteriocins. The growth rate of the bac- mutant was higher than that of the wild
      type at 5 and 37 degrees C but not at 25 or 30 degrees C. In salmon juice the
      maximum cell density of L. monocytogenes was suppressed 3 and 6 log by co-culture
      with C. piscicola A9b bac- and bac+, respectively, as compared with the control.
      Sterile filtered cultures of C. piscicola A9b bac- caused a limited suppression
      of the maximum cell density of L. monocytogenes similar to that observed when
      sterile buffer was added in equal amounts. Semi-purified carnobacteriocin B2
      caused a 3.5 log decline in viable cell count after 6 day of incubation in cold
      smoked salmon juice at 5 degrees C. High resistance level to carnobacteriocin B2
      was observed for L. monocytogenes cells exposed to semi-purified and in situ
      produced carnobacteriocin B2. CONCLUSIONS: The presence of bacteriocin production
      in C. piscicola enhances its inhibition of L. monocytogenes. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Due to the emergence of resistance, a bacteriocin negative
      lactic acid bacteria may be more suited for practical use as a bioprotective
      agent against L. monocytogenes in ready-to-eat foods.

PMID- 14678167
TI  - Characterization of closely related lactococcal starter strains which show
      differing patterns of bacteriophage sensitivity.
AB  - AIMS: To characterize a group of closely related Lactococcus lactis subsp. lactis
      casein starter strains used commercially, which differ in their sensitivity to
      bacteriophages isolated from the same industrial environment. METHODS AND
      RESULTS: Nine strains of L. lactis, six of which had been used as starter
      cultures for lactic casein manufacture, were shown to be closely related by
      pulsed-field gel electrophoresis and total DNA profiles. Nineteen phages which
      propagated on one or more of these starter strains were isolated from industrial
      casein whey samples. The phages were all small isometric-headed and could be
      divided into five groups on the basis of host range on the nine strains. Most of
      the phages did not give a PCR product with primers designed to detect the two
      most common lactococcal small isometric phage species (936 and P335). The hosts
      could be divided into six groups depending on their phage sensitivity. Plasmids
      encoding genes for the cell envelope associated PI-type proteinase, lactose
      metabolism and specificity subunits of a type I restriction/modification system
      were identified. CONCLUSIONS: This work demonstrates how isolates of the same
      starter strain may come to be regarded as separate cultures because of their
      different origins, and how these closely related strains may differ in some of
      their industrially relevant characteristics. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This situation may be very common among lactococci used as dairy starter
      cultures, and implies that the dairy industry worldwide depends on a small number
      of different strains.

PMID- 14678168
TI  - Comparison of contamination and growth of Mycobacterium avium subsp.
      paratuberculosis on two different media.
AB  - AIMS: The purpose of the study was to compare the growth of Mycobacterium avium
      subsp. paratuberculosis (Map) and the degree of contamination on Herrold's egg
      yolk medium (HEYM) and modified Lowenstein-Jensen medium (LJ). METHODS AND
      RESULTS: Culture of 2513 faecal samples from dairy cows was performed on each of
      the two media. The media were read after 5, 8 and 12 weeks of incubation.
      Overall, the proportion of contaminated samples was significantly higher on LJ
      (14.2%) than on HEYM (13.2%) after 12 weeks but the degree of contamination was
      slightly less on LJ. After 8 weeks of incubation, only 1.0% of the samples were
      Map positive in LJ with 4.9% on HEYM. After 12 weeks of incubation, 3.3% of the
      samples were Map positive in LJ whereas 6.9% were positive in HEYM. All suspect
      and culture positive samples were confirmed by IS900 PCR. CONCLUSIONS: HEYM
      supported growth of Map significantly better and faster than LJ, however it could
      not be determined conclusively which of the two media that provided the highest
      degree of decontamination when the incubation time was also included.
      SIGNIFICANCE AND IMPACT OF THE STUDY: HEYM should be the primary medium rather
      than LJ for detection of Map in cattle.

PMID- 14678169
TI  - Influence of the growth phase and culture medium on the survival of Mannheimia
      haemolytica during storage at different temperatures.
AB  - AIMS: To quantify the influence of the growth phase, storage temperature and
      nutritional quality of the plate count medium on the apparent viability of
      Mannheimia haemolytica during storage at different temperatures. METHODS AND
      RESULTS: Mannheimia haemolytica was grown in shake flasks and in aerobic
      continuous culture to investigate factors affecting cell viability during
      storage, which was determined using plate counts on different media and
      epifluorescence microscopy. The high specific death rates of cells harvested
      after cessation of exponential growth and stored at 22, 4, -18 and -75 degrees C
      could be related to the rapid onset of exponential death in batch cultures. Yeast
      extract supplementation of the culture medium increased the viability of cells at
      most of the above-mentioned storage temperatures. Of the total cell count in
      continuous culture, only 48% could be recovered on brain-heart infusion agar,
      whereas supplementation of the agar medium with foetal calf serum increased the
      plate count to 71% of the total count. CONCLUSIONS: Mannheimia haemolytica cells
      harvested from the exponential growth phase had the highest survival rate during
      storage at low temperatures. Plate count values also depended on the nutritional
      quality of the agar medium. SIGNIFICANCE AND IMPACT OF THE STUDY: Results
      presented here impact on the procedures for culture preservation and plate count
      enumeration of this fastidious animal pathogen.

PMID- 14678170
TI  - Dormant ascospores of Talaromyces macrosporus are activated to germinate after
      treatment with ultra high pressure.
AB  - AIMS: Ascospores of Talaromyces macrosporus are constitutively dormant and
      germinate after a strong external shock, classically a heat treatment. This
      fungus is used as a model system to study heat resistance leading to food
      spoilage after pasteurization. This study evaluates the effect of high pressure
      on the germination behaviour of these spores. METHODS AND RESULTS: Ascospore
      containing bags were subjected to ultra high pressure and spores were plated out
      on agar surfaces. Untreated suspensions showed invariably very low germination.
      Increased germination of ascospores occurred after short treatments at very high
      pressure (between 400 and 800 MPa). Activation is partial compared with heat
      activation and did not exceed 6.9% (65 times that of untreated suspensions) of
      the spore population. Maximum activation was attained shortly (10 s-3 min) after
      the pressure was applied and accompanied by cell wall deformations as judged by
      scanning electron microscopy. The spores observed in this study were harvested
      from cultures that were 39-58 days old. The maturity of spores at similar
      developmental stages was measured by assessing the heat resistance of ascospores.
      Between 20 and 40 days heat resistance increased 2.4-fold, but only an additional
      increase of 1.3-fold was observed at later stages (40-67 days). CONCLUSIONS: Our
      investigations show that high pressure constitutes a second type of shock that
      can activate heat-resistant ascospores to germinate. Activation is maximal after
      very short treatments and accompanied with changes in the cell wall structure.
      High-pressure activation is not the result of immaturity of the ascospores.
      SIGNIFICANCE AND IMPACT OF THE STUDY: These observations are relevant for the
      application of high pressure as a novel pasteurization method.

PMID- 14678171
TI  - Evaluation of novel beta-ribosidase substrates for the differentiation of Gram
      negative bacteria.
AB  - AIMS: To synthesize novel substrates for the detection of beta-ribosidase and
      assess their potential for the differentiation of Gram-negative bacteria. METHODS
      AND RESULTS: Two novel chromogenic substrates, 3',4'-dihydroxyflavone-4'-beta-D
      ribofuranoside (DHF-riboside) and 5-bromo-4-chloro-3-indolyl-beta-D
      ribofuranoside (X-riboside) were evaluated along with a known fluorogenic
      substrate, 4-methylumbelliferyl-beta-D-ribofuranoside (4MU-riboside). A total of
      543 Gram-negative bacilli were cultured on media containing either DHF-riboside
      or X-riboside. Hydrolysis of DHF-riboside or X-riboside resulted in the formation
      of clearly distinguishable black or blue-green colonies, respectively. Hydrolysis
      of 4MU-riboside was evaluated in a liquid medium in microtiter trays and yielded
      blue fluorescence on hydrolysis which was measured using fluorimetry. beta
      Ribosidase activity was widespread with 75% of strains, including 85.6% of
      Enterobacteriaceae, showing activity with at least one substrate. Genera that
      demonstrated beta-ribosidase activity included Aeromonas, Citrobacter,
      Enterobacter, Escherichia, Hafnia, Klebsiella, Morganella, Providencia,
      Pseudomonas, Salmonella and Shigella. In contrast, strains of Proteus spp.,
      Acinetobacter spp., Yersinia enterocolitica, Vibrio cholerae and Vibrio
      parahaemolyticus generally failed to demonstrate beta-ribosidase activity.
      CONCLUSIONS: The novel substrates DHF-riboside and X-riboside are effective for
      the detection of beta-ribosidase in agar-based media and may be useful for the
      differentiation and identification of Gram-negative bacteria. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This is the first report describing the application and
      utility of chromogenic substrates for beta-ribosidase. These substrates could be
      applied in chromogenic media for differentiation of Gram-negative bacteria.

PMID- 14678172
TI  - Biofilm formation and cell-to-cell signalling in Gram-negative bacteria isolated
      from a food processing environment.
AB  - AIMS: To investigate the biofilm-forming capacity and the production of quorum
      signals in Gram-negative bacteria isolated from a food production environment,
      and the possible correlation between both phenotypes. METHODS AND RESULTS: Sixty
      eight Gram-negative bacteria were isolated from equipment and working surfaces in
      a raw vegetable processing line, and tested for biofilm-forming capacity using an
      in vitro microplate assay. All isolates showed significantly higher biofilm
      forming capacity than Escherichia coli laboratory strain DH5alpha, which was
      included as a negative control, and differed up to 56-fold in relative biofilm
      forming capacity. Various assays based on reporter bacteria were used to detect
      quorum signals produced by the isolates. Twenty-six isolates produced autoinducer
      2, five isolates produced N-acyl-homoserine lactones (AHLs), and none produced
      the Pseudomonas quinolone signal. CONCLUSIONS: No correlation was found between
      in vitro biofilm-forming capacity and production of quorum signalling molecules
      among the 68 strains isolated from the raw vegetable processing line.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Several recent studies have shown a role of
      AHL-based quorum sensing in biofilm formation of specific Gram-negative bacterial
      strains. The current work shows that production of AHL and other quorum signals
      is not widespread in Gram-negative isolates from a raw vegetable processing line,
      and is not a general requirement for biofilm formation, at least in vitro.

PMID- 14678173
TI  - Expression analysis of putative arcA, arcB and arcC genes partially cloned from
      Lactobacillus plantarum isolated from wine.
AB  - AIMS: The aim of this paper was to study if homofermentative strains
      (Lacobacillus plantarum) capable of malolactic fermentation in wine can degrade
      arginine via the ADI pathway. METHODS AND RESULTS: Homofermentative lactic acid
      bacteria (LAB) isolated from a typical red wine were investigated for their
      ability to produce citrulline. Citrulline was formed suggesting that the arginine
      metabolism takes place via the arginine deiminase (ADI) pathway and not via the
      arginase/urease pathway. Ammonia was also detected with Nessler's reagent, and
      all the strains examined were able to produce ammonia. Identification of
      homofermentative LAB was performed using 16S ribosomal sequence analysis. The
      strains were further classified as belonging to L. plantarum species.
      Furthermore, the genes encoding for the three pathway enzymes (ADI, ornithine
      transcarbamylase, carbamate kinase) were partially cloned and gene expression was
      performed at two different pH values (3.6 and 4.5). CONCLUSIONS: The results
      suggest that citrulline production in wine, could be performed by
      homofermentative LAB. SIGNIFICANCE AND IMPACT OF THE STUDY: Homofermentative
      malolactic bacteria (L. plantarum) may degrade arginine through the ADI pathway.

PMID- 14678174
TI  - Inorganic compounds have dual effect on recombinant protein production: influence
      of anions and cations on serine alkaline protease production.
AB  - AIMS: Investigation of concerted effects of cations, i.e. Mg2+ and Mn2+, in
      combination with their anions, i.e. sulphate, chloride and acetate (Ac), on the
      physiology of Bacillus licheniformis carrying pHV1431::subC to improve the
      fermentation medium for serine alkaline protease (SAP) production, whereupon,
      determination of the acid that can be used in pH control. METHODS AND RESULTS:
      The cell concentrations increased with the increase in MnSO4 and Mn(Ac)2
      concentrations, and the highest values were obtained at Co(MnSO4) = 0.20 mmol l-1
      and Co(Mn(CH3COO)2) = 4.0 mmol l-1, as 2.3 and 2.2 g l-1, respectively. However,
      Co(MnCl2) did not influence biomass concentration. SAP production was inhibited
      with MnCl2 after Co(MnCl2) = 0.60 mmol l-1, but with MnSO4 SAP production was
      inhibited drastically. Whereas, at high concentrations of Mn(Ac)2 SAP production
      increased and the highest activity was obtained as ASAP = 1285 U ml-1 at t = 65
      h. With the Mg compounds, cell concentrations increased with the increase in the
      concentrations of MgSO4, MgCl2 and Mg(Ac)2; and the anions did not show any
      influence on the cell growth. Similar to the results of Mn compounds, the glucose
      consumption rate increased with the increase in MgSO4 and MgCl2 concentrations;
      contrariwise, decreased with the increase in Mg(Ac)2 concentrations, due to the
      use of acetate as the second carbon source. Co(MgSO4) = 0.40 mmol l-1, Co(MgCl2)
      = 1.60 mmol l-1 and Co(Mg(Ac)2) = 0.40 mmol l-1 were the optimum concentrations
      separately, and the highest SAP activity was obtained with Mg(Ac)2 as ASAP = 1338
      U ml-1 at t = 47 h. Consequently, ion acetate and its acid HAc appear,
      respectively, as the superior anion for the essential cations and the control
      agent for pH control in the bioreactor. Finally, optimum initial concentrations
      and the concerted effects of Mg(Ac)2 and Mn(Ac)2 were investigated, and the
      optimum concentrations were found respectively as 0.40 and 0.80 mmol l-1, while
      the maximum activity was obtained as ASAP = 1010 U ml-1 at a shortened
      cultivation time of t = 39 h. CONCLUSIONS: Mn(Ac)2 and Mg(Ac)2 together enhanced
      the cell formation and SAP synthesis rates, moreover, SAP synthesis started at an
      earlier cultivation time. SIGNIFICANCE AND IMPACT OF THE STUDY: Each inorganic
      compound with its cation and anion has dual effect on the metabolism. Mg2+ and
      Mn2+ at their specific concentrations influence the regulation of the pathways
      that might cause better coupling of supply and demand for the amino acids on the
      basis of the amino acid composition of the enzyme molecule.

PMID- 14678175
TI  - Cross-resistance to antibiotics of Escherichia coli adapted to benzalkonium
      chloride or exposed to stress-inducers.
AB  - AIMS: To study the effects of adaptation and stress on the resistance to
      benzalkonium chloride (BC) and cross-resistance to antibiotics in Escherichia
      coli. METHODS AND RESULTS: Precultivation of E. coli ATCC 11775 and E. coli DSM
      682 in the presence of subinhibitory concentrations of BC or stress inducers
      (salicylate, chenodeoxycholate and methyl viologen) resulted in higher minimum
      inhibitory concentration (MIC) of BC and chloramphenicol (CHL). Adaptation to
      growth in sixfold of the initial MIC of BC resulted in stable BC resistance and
      enhanced tolerance to several antibiotics and ethidium bromide (EtBr). The MIC of
      CHL increased more than 10-fold for both strains. Enhanced efflux of EtBr in
      adapted E. coli ATCC 11775 indicated that the observed resistance was due to
      efflux. Changes in outer membrane protein profiles were detected in the BC
      adapted cells. There were no indications of lower membrane permeability to BC.
      CONCLUSIONS: Induction of stress response or gradual adaptation to BC or CHL
      results in acquired cross-tolerance between BC and antibiotics in E. coli.
      Enhanced efflux was one of the observed differences in adapted cells.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Provided not taking due precautions,
      extensive use of disinfectants could lead to emergence of antibiotic-resistant
      isolates.

PMID- 14678176
TI  - Characterization of urease genes cluster of Streptococcus thermophilus.
AB  - AIMS: The milk acidification rate of Streptococcus thermophilus strains can be
      affected by several factors, one of which is the hydrolysis of urea by the urease
      complex. To evaluate the technological suitability of S. thermophilus strains
      deprived of urease activity in milk fermentation, the genetic cluster related to
      urease enzymatic activity has been characterized in the type strain DSM 20167T.
      METHODS AND RESULTS: Amplification of the urease genes of S. thermophilus DSM
      20167T was developed on the basis of the urease gene cluster of the
      phylogenetically related S. salivarius. Nucleotide sequencing revealed the
      presence of eight open reading frames, which were most homologous to ureABC
      (structural genes) and ureI, ureEFGD (accessory genes) of S. salivarius and other
      ureolytic bacteria. Reverse transcriptase PCR experiments were in agreement with
      an operon organization for the eight genes (ureIABCEFGD). A food grade mutant A16
      (DeltaureC3) with a 693 bp in-frame deletion in ureC gene exhibited a urease
      negative (Ure-) phenotype. Unlike the wild-type strain, the acidification rate of
      the mutant in reconstituted skimmed milk was not affected by the presence of urea
      or nickel ions. A small-scale yoghurt fermentation trials were carried out using
      the wild-type or the Ure- mutant A16 (DeltaureC3) in co-culture with
      Lactobacillus delbrueckii subsp. bulgaricus ATCC 11842 in presence of urea. The
      result obtained underlines that when the Ure- mutant was used as a co-starter the
      acidification rate was higher than that obtained using the wild-type strain.
      CONCLUSIONS: The study provides the first genetic characterization and the
      technological implication of S. thermophilus DSM 20617T urease activity.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The detrimental effect of ureolytic
      activity on the rate of milk acidification was evaluated and superseded using a
      food-grade Ure- recombinant strain. Small-scale yoghurt production trials
      highlighted the positive role of a Ure-S. thermophilus mutant as a co-starter in
      milk fermentations. Moreover, the vector pMI108 developed for the construction of
      the Ure- strain, should be considered as a potential tool for the generation of
      Ure- dairy S. thermophilus strains selected for other relevant technological
      properties but characterized by the undesirable ureolytic phenotype.

PMID- 14678177
TI  - Laparoscopic nephropexy: treatment outcome and quality of life.
AB  - BACKGROUND: The recent introduction of laparoscopic procedures has markedly
      altered urological surgery. Laparoscopic nephropexy has attracted the attention
      of urologists as a treatment for nephroptosis. Herein, we describe our
      experiences and quality-of-life outcome of laparoscopic nephropexy and discuss
      its indications and surgical techniques. METHODS: From May 1998 to February 2002,
      six female patients, ranging in age from 20 to 64 years (median age 39.8 years),
      with symptomatic nephroptosis underwent laparoscopic nephropexy. Mean
      preoperative downward kidney displacement was 2.25 vertebral bodies (range 2-2.5)
      and all affected kidneys were tilted at orthostasis. One patient underwent
      nephropexy through the transperitoneal approach and the remaining patients
      underwent nephropexy through the retroperitoneal approach. To evaluate surgical
      results, postoperative follow-up interview (pain visual analog scale and the
      short-form 36 (SF-36) health survey questionnaire) and objective examinations
      were performed. RESULTS: All procedures were accomplished without complication.
      Postoperative intravenous pyelography correctly confirmed fixed kidney in both
      supine and erect positions. All patients reported an improvement of symptoms
      approximately 1 month after nephropexy and no symptoms have recurred during the
      follow-up period (range 6.3-50.7 months). On the SF-36, two domains, including
      role limitations due to emotional problems (RE) and mental health (MH), exhibited
      significant improvement postoperatively (P = 0.0405 and P = 0.0351,
      respectively). CONCLUSIONS: Laparoscopic, in particular retroperitoneoscopic,
      nephropexy yields excellent outcomes and greatly improves general health-related
      quality of life, particularly mental status, as a minimally invasive treatment
      for symptomatic nephroptosis.

PMID- 14678178
TI  - Retroperitoneoscopic heminephroureterectomy for children with duplex anomaly:
      Initial experience.
AB  - OBJECTIVES: To evaluate the feasibility of retroperitoneoscopic
      heminephroureterectomy for children with duplex anomaly. METHODS:
      Retroperitoneoscopic heminephroureterectomy was performed in five children (four
      girls and one boy) with complete duplication of the ureter, of whom four (age
      range 1-5 years; mean age 3.3 years) had upper pole ectopic megaureters and one
      (3 years old) had an upper pole megaureter with ureterocele. In the patient with
      ureterocele, distal ureterectomy and ureterocelectomy were performed by
      Pfannenstiel incision. RESULTS: The mean operation time was 346 min (range 270
      450 min) in the four patients with ectopic megaureter and 420 min (330 min for
      heminephroureterectomy) in the patient with ureterocele. The mean estimated blood
      loss was 43 mL (range 5-100 mL) in the four patients with ectopic megaureter and
      40 mL in the patient with ureterocele. No postoperative complications were
      observed. Postoperative intravenous pyelography showed normal pyelogram and renal
      function of the preserved lower pole in all cases. CONCLUSIONS:
      Retroperitoneoscopic heminephroureterectomy for children is feasible, safe and
      has good postoperative results, including cosmetic results. However, the
      operation time needs to be reduced.

PMID- 14678179
TI  - Foods and beverages in relation to urothelial cancer: case-control study in
      Japan.
AB  - BACKGROUND: The roles of several foods and beverages in the development of
      bladder cancer remain unclear. METHODS: We undertook a hospital-based case
      control study at Aichi Cancer Center Hospital, Japan. Subjects included 124 men
      and women (bladder cancer cases) with newly diagnosed cancers of the renal pelvis
      (n = 5), ureter (n = 6) or bladder (n = 113) and 620 age- and sex-matched, cancer
      free outpatients (controls) presenting at the hospital in the period from 1994 to
      2000. Smoking-adjusted odds ratios (OR) were estimated to assess the strength of
      associations between self-reported intake of foods or drinks and bladder cancer
      risk, using conditional logistic models. RESULTS: We found a decreased risk in
      relation to frequent intake of green-yellow vegetables; the OR for the highest
      intake score compared with the lowest was 0.54 (95% confidence interval [CI] 0.29
      0.99). The OR for carrot intake of >/=5 times/week compared with </=1-3
      times/month was 0.41 (95% CI 0.16-1.01) and a decreasing risk with increasing
      consumption of green vegetables was also detected (P for trend = 0.063). Inverse
      associations between black tea, eggs and meat and risk were also suggested,
      whereas moderate drinkers of green tea (5-9 cups/day) showed an elevated risk.
      Coffee and milk consumption did not appear to exert any influence. CONCLUSIONS:
      Those with an increased risk of bladder cancer, such as smokers, may benefit from
      increasing their consumption of green-yellow vegetables.

PMID- 14678180
TI  - Alpha-blocker test: alternative to pressure-flow study of bladder outlet
      obstruction and detrusor contractility in patients without an enlarged prostate.
AB  - OBJECTIVES: We investigated whether the cause of urinary disturbance in men with
      a prostate volume < or =20 mL can be determined by analyzing the efficacy of
      alpha1-adrenoceptor antagonist (alpha-blocker) treatment. METHODS: Thirty-five
      men who were >50 years of age, with an International Prostate Symptom Score
      (IPSS) > or =8 points, a quality of life (QOL) index > or =2 points and a
      prostate volume </=20 mL were enrolled in the non-enlarged prostate group. Twenty
      six men who met the above conditions but who had a prostate volume >20 mL served
      as controls. The alpha1-adrenoceptor antagonist tamsulosin was administered at a
      dose of 0.2 mg/day for 4 weeks. Results for the IPSS, QOL index, free flowmetry
      and pressure-flow studies were obtained before and after tamsulosin
      administration. RESULTS: In both groups, tamsulosin improved the IPSS and QOL
      index and the bladder outlet obstruction index (BOOI) was lowered without
      reducing the bladder contractility index (BCI). No parameter showed a significant
      difference in treatment efficacy between the two groups. In the non-enlarged
      prostate group, both the pretreatment BOOI and BCI correlated with the efficacy
      of treatment in improving maximum flow rate (Qmax). In the enlarged prostate
      group, BOOI and BCI did not correlate with Qmax. When Qmax was improved by > or
      =3.5 mL/s, the positive predictive value for both pretreatment BOOI >40 and BCI
      >100 was 100% in the non-enlarged prostate group. CONCLUSIONS: The alpha-blocker
      test is one method to assess the presence of bladder outlet obstruction and the
      state of detrusor contractility in men without an enlarged prostate.

PMID- 14678181
TI  - Marzouk skin tag two-stage urethroplasty for the repair of complex cases of
      hypospadias.
AB  - BACKGROUND: Cases of hypospadias with severe chordee and deficient skin, as well
      as those for re-do hypospadias or fistula repair, are considered complex cases.
      Depending on the degree of complexity of the defect, a two-stage procedure may
      still be advisable. The present paper describes the so-called Marzouk skin tag
      urethroplasty as a new two-stage procedure advisable for use in such difficult
      cases. METHODS: The Marzouk skin tag urethroplasty procedure was performed on 16
      complex cases. The first stage consists of urethral mobilization plus the double
      buttonhole procedure (designed by the author) to form a midline ventral skin tag
      proximal to an advanced hypospadiac orifice. This skin tag is fashioned, 6 months
      later, by the author's special techniques (type I in 12 patients and type II in
      four patients) to form the neourethral tube and its coverage with minimal
      dissection. RESULTS: The operation resulted in a straight penis with neomeatus at
      the glans top in all 16 cases without significant complications. Both type I and
      II procedures give good functional results. The type I procedure has a superior
      cosmetic result. The follow-up period ranged from 4 to 8 months. CONCLUSIONS: The
      double-buttonhole modification can solve the problem of deficient skin and
      simplify a safe second-stage procedure. The Marzouk skin tag operation (types I
      and II) can be an additional option to be used when indicated.

PMID- 14678182
TI  - Bulbocavernosus reflex during the micturition cycle in normal male subjects.
AB  - BACKGROUND: To investigate normal changes in the bulbocavernosus reflex (BCR)
      during the micturition cycle, we examined the change in BCR during the
      micturition cycle using an evoked potential reaction of the BCR (BCR-EP).
      METHODS: Fourteen normal subjects were examined in the study. The BCR-EP was
      recorded at empty bladder, filled bladder, during voiding and at empty bladder
      after voiding. To elicit the BCR-EP, the dorsal nerve of the penis was stimulated
      by two ring electrodes and an electromyogram of the external urethral sphincter
      was recorded. The maximum amplitude was measured to evaluate changes in the BCR.
      RESULTS: The amplitude of the BCR was increased by bladder filling and the ratio
      of the amplitude at filled bladder/amplitude at empty bladder was 1.32 +/- 0.39.
      The stable BCR-EP elicited by stimulation at empty bladder disappeared during
      voluntary voiding in 13 of 14 subjects. However, as stimulation was increased in
      seven subjects, the BCR-EP was again seen clearly. CONCLUSIONS: The BCR varies
      during the micturition cycle, although in normal subjects this variation occurs
      within a relatively narrow range. Changes in the BCR out of the normal range
      (e.g. large acceleration by bladder filling or insufficient inhibition during
      voiding) could suggest the existence of neurogenic disease.

PMID- 14678183
TI  - Detection of circulating MUC7-positive cells by reverse transcription-polymerase
      chain reaction in bladder cancer patients.
AB  - BACKGROUND: To determine whether MUC7 gene expression can be used as a bladder
      cancer marker in peripheral blood. METHODS: Nested reverse transcription
      polymerase chain reaction (RT-PCR) was performed on four types of bladder cancer
      cell lines (RT4, T24, EJ-1 and TCC) and the peripheral blood of 38 (31
      superficial disease and seven invasive disease) bladder cancer patients and 18
      subjects with urinary tract infections or other non-malignant conditions to
      determine the expression of MUC7. RESULTS: No MUC7 gene expression was detected
      in control subjects. MUC7-positive cells were detected in all bladder cancer cell
      lines and in 18 of 38 (47.4%) peripheral blood samples of bladder cancer
      patients. Based on the tumor stage, MUC7 was detected in 11 of 29 (37.9%)
      patients with superficial disease (Ta and T1) and in seven of nine (77.7%)
      invasive disease patients (>/=T2). There was a significant difference between
      superficial and invasive disease (P = 0.042). Based on tumor grade, we could not
      detect MUC7 in five patients with grade 1, in five of 15 patients (33.3%) with
      grade 2 and in 13 of 18 patients (72.2%) with grade 3. There was a significant
      difference between grades 1 and 3 (P = 0.007) and grades 2 and 3 (P = 0.025).
      CONCLUSIONS: These results suggest that MUC7 is a highly specific marker for
      bladder cancer and may be a useful method for the molecular staging and
      management of bladder cancer.

PMID- 14678184
TI  - Coexistence of renal replacement lipomatosis with xanthogranulomatous
      pyelonephritis.
AB  - We report on a case of coexistence of replacement lipomatosis with
      xanthogranulomatous pyelonephritis (XGP) in the same kidney associated with
      staghorn calculi. A 63-year-old man was admitted to hospital complaining of a
      right abdominal mass. Computed tomography (CT) showed renal parenchymal atrophy
      with extremely increased perirenal fat. Right nephrectomy was performed.
      Postoperative diagnosis was renal replacement lipomatosis with XGP. Renal
      replacement lipomatosis and XGP have several similarities in terms of clinical
      background and CT findings. Sometimes it is difficult to differentiate them from
      malignant diseases. It is extremely rare that both conditions coexist in the same
      kidney. To our knowledge, only one such case has been reported.

PMID- 14678185
TI  - Clinically isolated cerebellar metastasis of renal pelvic urothelial cancer.
AB  - A 70-year-old man who had undergone radical surgery for renal pelvic transitional
      cell carcinoma 9 months previously developed solitary cerebellar metastasis.
      Despite neurosurgical removal, the patient died and post-mortem pathological
      examination revealed microscopic metastatic lesions within microvessels of the
      lung. No other lesion, including local residual cancer, was detected.

PMID- 14678186
TI  - Prenatal diagnosis of congenital mesoblastic nephroma associated with renal
      hypertension in a premature child.
AB  - In the present article, we report, for the first time, a prenatal diagnosis of a
      congenital mesoblastic nephroma in combination with a post-partum hyperreninemia
      with hypertension. A newborn was delivered at 35 weeks gestation who had an
      intrauterine diagnosis of a renal mass as early as 32 weeks gestational age by
      ultrasound examination. Tumor nephrectomy was performed on day 11 after delivery
      when an increase in hypertension was observed in the newborn.

PMID- 14678187
TI  - Perinephric urinoma secondary to neurogenic bladder with vesicoureteral reflux:
      report of an adult case.
AB  - We report a case of infectious perinephric urinoma in a 73-year-old woman who had
      a neurogenic bladder with vesico-ureteral reflux. The patient was admitted to our
      emergency room with right lumbago and high fever. Ultrasounds and computed
      tomography demonstrated a right large perinephric cystic mass, bilateral
      hydronephrosis and much residual urine. Percutaneous drainage of the cystic mass
      was performed with an indwelling urethral catheter. The content of the mass was
      urine infected with Escherichia coli. Antibiotic therapy was performed
      successfully and we then examined the cause of the urinoma. A urodynamic study
      demonstrated a low-compliance small bladder and detrusor-sphincter dyssynergia. A
      voiding cystourethrogram revealed right grade III vesicoureteral reflux. The
      patient was unable to be cleared with intermittent catheterization and had an
      indwelling urethral catheter inserted. In 1 year, the voiding cystourethrogram
      showed no vesicoureteral reflux and the patient was well with no evidence of
      recurrent urinoma without the urethral catheter. There have been only two
      reported cases of urinoma caused by neurogenic bladder with vesico-ureteral
      reflux in children and this is the first case reported in an adult.

PMID- 14678188
TI  - Lipomatosis of the bladder presenting as bladder cancer.
AB  - A case of bladder lipomatosis in an 81-year-old man is presented. The
      preoperative diagnosis was bladder tumor. A transurethral resection of the
      bladder was performed and a pathological examination revealed lipomatosis of the
      bladder. This entity is extremely rare and, to our knowledge, this is the second
      case reported in the English published works.

PMID- 14678189
TI  - Recurrent epididymo-orchitis caused by posterior urethral valve associated with
      imperforate anus.
AB  - Epididymo-orchitis is an uncommon complication of imperforate anus. A 14-year-old
      boy who received surgical repair for imperforate anus was diagnosed with right
      epididymo-orchitis. Intravenous pyelography showed a right solitary kidney.
      Posterior urethral valve, reflux of contrast medium to the ejaculatory duct and
      incomplete duplicate urethra were suspected from voiding cystourethrography.
      Valve ablation was performed to prevent the recurrence of epididymo-orchitis.
      Improvement of urinary force was achieved and the patient has been free of
      recurrence during a 2-year follow up. For the patient with imperforate anus, we
      should evaluate not only anorectal function, but also the genitourinary tract in
      order to preserve renal function and fertility.

PMID- 14678190
TI  - Tiny nodule in the testicle: case report of a sertoli cell tumor.
AB  - Sex cord-stromal tumors of the testis are rare. We report on a small Sertoli cell
      tumor in the testicle. According to published reports, a nodular lesion on the
      testicle has a variety of differential diagnoses. Preoperatively, it is very
      difficult to differentiate between a tumorous lesion and an inflammatory change.
      When a tiny nodule in the testicle is encountered, we propose limited, testicular
      sparing surgery according to the frozen section diagnosis.

PMID- 14678191
TI  - T lymphocyte dependence of the antibody response to 'T lymphocyte independent
      type 2' antigens.

PMID- 14678192
TI  - Ca2+ influx shutdown during neutrophil apoptosis: importance and possible
      mechanism.

PMID- 14678193
TI  - The innate immune system: gatekeeper to the female reproductive tract.

PMID- 14678194
TI  - Anti-CD3 sFv/IL-18 fusion DNA for allergy therapy.

PMID- 14678195
TI  - Co-administration of CD40 agonistic antibody and antigen fails to overcome the
      induction of oral tolerance.
AB  - T-cell stimulation in the absence of a second, costimulatory signal can lead to
      anergy or deletion. There is growing evidence that peripheral tolerance to an
      exogenous antigen might be caused by the lack of costimulatory molecules on
      antigen-presenting cells (APCs). In the present study, we examined whether
      tolerance against orally administered antigen could be reversed by maturation of
      APCs via CD40 signalling. Monoclonal antibody (mAb) to CD40 efficiently induced
      costimulatory molecules on APCs. Treatment with anti-CD40 mAb potentiated the
      division of ovalbumin-specific T cells in response to oral ovalbumin in secondary
      lymphoid organs. However, such treatment did not prolong the presentation of oral
      ovalbumin on APCs. Surprisingly, treatment of anti-CD40 mAb at the time of oral
      administration of ovalbumin did not reverse the induction of tolerance to
      ovalbumin in either the high- or low-dose regimens. Furthermore, the induction of
      oral tolerance in our model is not the result of negative signalling by cytotoxic
      T-lymphocyte antigen-4. These results indicate that tolerance for oral antigen
      could be established regardless of APC maturation by a CD40-specific mAb,
      suggesting that there could be a unique mechanism to regulate immunity versus
      tolerance to encountered antigen in the gut-associated lymphoid tissue.

PMID- 14678196
TI  - Efficient induction of T helper type 1-mediated immune responses in antigen
      primed mice by anti-CD3 single-chain Fv/interleukin-18 fusion DNA.
AB  - Two types of T helper (Th) cells - Th1 and Th2 - play different roles in
      protection and immunopathology. The Th1 cell-mediated immune response plays an
      important role in inducing the host defence against intracellular bacteria and
      also in cancer immunotherapy. To effectively induce Th1 immune responses, we
      constructed a mammalian expression plasmid (pAnti-CD3sFv/IL-18) carrying a fusion
      gene in which anti-CD3 single-chain Fv (sFv) cDNA, the smallest unit of antibody
      recognizing the CD3 epsilon moiety of the T-cell receptor, was covalently linked
      to mature interleukin (IL)-18 cDNA. Intramuscular injection of ovalbumin (OVA)
      sensitized BALB/c mice with pAnti-CD3sFv/IL-18 DNA efficiently increased the
      production of both OVA-specific interferon-gamma and anti-OVA immunoglobulin G2a,
      compared to injection with pAnti-CD3sFv DNA. In addition, pAnti-CD3sFv/IL-18 was
      more efficient than a mixture of pAnti-CD3sFv + pIL-18 in inducing OVA-specific,
      Th1 immune responses and also in inhibiting OVA-specific, IL-4 production. These
      studies indicate that vaccination with pAnti-CD3sFv/IL-18 fusion DNA efficiently
      induces the Th1 immune response in antigen-sensitized mice.

PMID- 14678197
TI  - Impact of cAMP on the T-cell response to type II collagen.
AB  - There is considerable interest in the possible use of cAMP-elevating agents in
      the treatment of autoimmune diseases such as rheumatoid arthritis. The objective
      of this study was to evaluate the impact of different cAMP-elevating agents on
      the T-cell response to type II collagen within the context of collagen-induced
      arthritis, a murine model of rheumatoid arthritis. Spleen cells or lymph node
      cells from type-II-collagen-immunized DBA/1 mice were cultured in the presence of
      type II collagen plus one of five different cAMP-elevating agents: rolipram,
      forskolin, prostaglandin E2, 8-bromo-cAMP, or cholera toxin. Levels of interferon
      gamma (IFN-gamma), interleukin-4 (IL-4) and IL-5 were measured in culture
      supernatants by enzyme-linked immunosorbent assay. All of the cAMP-elevating
      agents tested were found to profoundly suppress IFN-gamma production in a dose
      dependent manner. IL-4 and IL-5 production was slightly up-regulated at low
      concentrations of the cAMP-elevating agents and was modestly suppressed at the
      highest concentrations of cAMP-elevating agents. Experiments were then carried
      out to determine whether T cells were directly affected by cAMP-elevating agents
      or whether the immunomodulatory effects were mediated via antigen-presenting
      cells. Pulsing T cells alone for a brief period with cholera toxin produced an
      almost identical effect to pulsing antigen-presenting cells alone, i.e. down
      regulation of proliferation, down-regulation of IFN-gamma production with little
      effect on IL-5 production. It was concluded that cAMP-elevating agents suppressed
      T helper type 1 responses to type II collagen to a greater extent than T helper
      type 2 responses. The cAMP-elevating agents could directly influence the activity
      of T cells but, in addition, influenced the ability of antigen-presenting cells
      to support T helper type 1 responses.

PMID- 14678198
TI  - Differential production of cytokines, reactive oxygen and nitrogen by bovine
      macrophages and dendritic cells stimulated with Toll-like receptor agonists.
AB  - Toll-like receptors (TLR) have been described as partially sharing signalling
      pathways but showing unique ligand specificity and tissue distribution. Here, the
      response of bovine macrophages (Mphi) and dendritic cells (DC), both derived from
      monocytes, was compared by exposing them to the TLR-specific ligands
      lipopolysaccharide, poly(I:C)-double-stranded RNA, and CpG-DNA, as well as
      inactivated Gram-negative and Gram-positive bacteria, shown to bind to TLR. The
      production of NO, superoxide anion, interleukin-10 (IL-10), IL-12 and tumour
      necrosis factor (TNF) was determined. Compared to monocytes, Mphi expressed more
      TLR2 and similar levels of TLR4 mRNA transcripts, as analysed by quantitative
      polymerase chain reaction, whereas DC expressed reduced amounts. Although both DC
      and Mphi recognized the TLR ligands, dramatic differences were seen in their
      reaction pattern to them. Both cell types responded with the production of TNF,
      but DC produced more IL-12, whereas Mphi produced more IL-10, regardless of the
      TLR agonist used. Co-stimulation with interferon-gamma influenced the amount of
      cytokine production, but did not alter the cell type-specific response pattern.
      Compared to Mphi, DC produced > 10 times less NO upon triggering with TLR
      ligands. In addition, DC produced superoxide anion to opsonized and non-opsonized
      zymosan, but not to phorbol 12-myristate 13-acetate, a response pattern confirmed
      for human Mphi and DC, respectively. Different protein kinase C isoforms and
      extracellular signal-regulated kinase patterns were detected in cell lysates of
      resting and stimulated Mphi and DC. Collectively, our results point to profound
      differences in pathogen-derived signal-response coupling occurring commensurate
      with distinct functions carried out by Mphi or DC.

PMID- 14678199
TI  - In vivo, RFX5 binds differently to the human leucocyte antigen-E, -F, and -G gene
      promoters and participates in HLA class I protein expression in a cell type
      dependent manner.
AB  - We analysed the regulation of human leucocyte antigen (HLA)-E, -F and -G genes,
      focusing on the SXY module, a promoter region that controls major
      histocompatibility complex (MHC) class II expression and participates in the
      expression of classical HLA class I molecules. It comprises the X1, X2 and Y
      boxes, bound by RFX, X2-BP/ATF/CREB and NFY factors, respectively. The complex
      recruits the master control factor CIITA. The SXY module is conserved in HLA-E
      and HLA-F gene promoters, whereas in the HLA-G promoter, the only conserved boxes
      are S and X1. Chromatin immunoprecipitation assays, performed on HLA-G positive
      and negative cell lines, demonstrated the in situ binding of RFX5 and CIITA to
      HLA-E and HLA-F, but not to HLA-G, promoters. In B cells from bare lymphocyte
      syndrome patients lacking RFX5 or CIITA, we observed lower steady-state levels of
      HLA-E and HLA-F transcripts but did not find any significant decrease in the cell
      surface expression of HLA-E/classical HLA class I. In RFX5-deficient fibroblasts,
      the cell-surface expression of HLA molecules was decreased. RFX5 and CIITA are
      thus not involved in HLA-G expression and their importance for the surface
      expression of HLA-E/classical HLA class I molecules may vary depending on the
      cell type.

PMID- 14678200
TI  - Rhesus macaque antibody molecules: sequences and heterogeneity of alpha and gamma
      constant regions.
AB  - Rhesus macaques (Macaca mulatta) are extensively used in vaccine development.
      Macaques infected with simian immunodeficiency viruses (SIV) or simian-human
      immunodeficiency viruses (SHIV) are the best animal model currently available for
      acquired-immune-deficiency-syndrome-related studies. Recent results emphasize the
      importance of antibody responses in controlling HIV and SIV infection. Despite
      the increasing attention placed on humoral immunity in these models, very limited
      information is available on rhesus macaque antibody molecules. Therefore, we
      sequenced, cloned and characterized immunoglobulin gamma (IGHG) and alpha (IGHA)
      chain constant region genes from rhesus macaques of Indian and Chinese origin.
      Although it is currently thought that rhesus macaques express three IgG
      subclasses, we identified four IGHG genes, which were designated IGHG1, IGHG2,
      IGHG3 and IGHG4 on the basis of sequence similarities with the four human genes
      encoding the IgG1, IgG2, IgG3 and IgG4 subclasses. The four genes were expressed
      at least at the messenger RNA level, as demonstrated by real-time reverse
      transcription polymerase chain reaction (RT-PCR). The level of intraspecies
      heterogeneity was very high for IGHA genes, whereas IGHG genes were remarkably
      similar in all animals examined. However, single amino acid substitutions were
      present in IGHG2 and IGHG4 genes, indicating the presence of IgG polymorphism
      possibly resulting in the expression of different allotypes. Two IgA alleles were
      identified in several animals and RT-PCR showed that both alleles may be
      expressed. Presence of immunoglobulin gene polymorphism appears to reflect the
      unusually high levels of intraspecies heterogeneity already demonstrated for
      major histocompatibility complex genes in this non-human primate species.

PMID- 14678202
TI  - The classical and alternative pathways of complement activation play distinct
      roles in spontaneous C3 fragment deposition and membrane attack complex (MAC)
      formation on human B lymphocytes.
AB  - The contributions of the classical (CP) and alternative (AP) pathways of
      complement activation to the spontaneous deposition of C3 fragments and the
      formation of membrane attack complexes (MAC) on human B lymphocytes, were
      assessed by incubating peripheral blood mononuclear cells with autologous serum
      in the absence and presence of selective inhibitors of the AP and CP,
      respectively. While the total amount of C3 fragments deposited was relatively
      unaffected by blocking either pathway individually, deposition was virtually
      abrogated by their combined blockade. A marked difference was observed, however,
      in the nature of the fragments deposited as a result of CP and AP activation: C3b
      fragments deposited via the CP were extensively ( approximately 90%) converted to
      the terminal degradation product, C3dg, whereas about 50% of those deposited by
      the AP persisted as C3b/iC3b fragments. The extent of MAC formation was also
      found to be highly pathway dependent, with the AP being about 15-fold more
      efficient at initiating this process than the CP. A model accounting for the
      effectiveness of the AP in both preserving C3 fragment integrity and initiating
      MAC is presented.

PMID- 14678201
TI  - Nuclear factor-kappaB contributes to interleukin-4- and interferon-dependent
      polymeric immunoglobulin receptor expression in human intestinal epithelial
      cells.
AB  - Polymeric immunoglobulins (pIgs) that are present at mucosal surfaces play key
      roles in both the innate and adaptive immune responses. These pIgs are delivered
      to the mucosal surface via transcytosis across the epithelium, a process mediated
      by the polymeric immunoglobulin receptor (pIgR). Previous studies demonstrate
      that expression of the pIgR is regulated by multiple immunomodulatory factors
      including interleukin-4 (IL-4) and interferon-gamma (IFN-gamma). In studies using
      human intestinal epithelial cells (HT29), multiple inhibitors of the
      transcription factor nuclear factor-kappaB (NF-kappaB), including a dominant
      negative IkappaBalpha-serine mutant, inhibited both IL-4- and IFN-dependent
      increases in pIgR expression. Under identical conditions, NF-kappaB inhibitors
      had no effect on cytokine-dependent increases in expression of the transcription
      factor interferon regulatory factor-1. Over-expression of the IkappaBalpha-serine
      mutant also inhibited reporter gene expression in response to IL-4, TNF-alpha, IL
      1beta, and in some cases IFN-gamma using constructs with sequences from the pIgR
      promoter. Reduced levels of pIgR were observed even when inhibitors were added
      >/=24 hr after cytokines suggesting that prolonged activation of NF-kappaB is
      required. Finally, reporter gene studies with NF-kappaB enhancer elements
      indicated that IFN-gamma alone and IL-4 in combination with other cytokines
      activated NF-kappaB in HT29 cells. Together, these studies provide additional
      insight into the signalling pathways that contribute to expression of the pIgR, a
      critical player in mucosal immunity.

PMID- 14678203
TI  - Surfactant protein A, an innate immune factor, is expressed in the vaginal mucosa
      and is present in vaginal lavage fluid.
AB  - Surfactant protein A (SP-A), first identified as a component of the lung
      surfactant system, is now recognized to be an important contributor to host
      defence mechanisms. SP-A can facilitate phagocytosis by opsonizing bacteria,
      fungi and viruses, stimulate the oxidative burst by phagocytes and modulate pro
      inflammatory cytokine production by phagocytic cells. SP-A can also provide a
      link between innate and adaptive immune responses by promoting differentiation
      and chemotaxis of dendritic cells. Because of the obvious relevance of these
      mechanisms to the host defence and 'gate keeping' functions of the lower genital
      tract, we examined human vaginal mucosa for SP-A protein and transcripts and
      analysed vaginal lavage fluid for SP-A. By immunocytochemistry, SP-A was
      identified in two layers of the vaginal epithelium: the deep intermediate layer
      (the site of newly differentiated epithelial cells); and the superficial layer
      (comprising dead epithelial cells), where SP-A is probably extracellular and
      associated with a glycocalyx. Transcripts of SP-A were identified by Northern
      blot analysis in RNA isolated from vaginal wall and shown, by sequencing of
      reverse transcription-polymerase chain reaction products, to be derived from each
      of the two closely related SP-A genes, SP-A1 and SP-A2. SP-A was identified in
      vaginal lavage fluid by two-dimensional gel electrophoresis, and confirmed by
      mass spectrometry. This study provides evidence, for the first time, that SP-A is
      produced in a squamous epithelium, namely the vaginal mucosa, and has a
      localization that would allow it to contribute to both the innate and adaptive
      immune response. The findings support the hypothesis that in the vagina, as in
      lung, SP-A is an essential component of the host-defence system. A corollary
      hypothesis is that qualitative and quantitative alterations of normal SP-A may
      play a role in the pathogenesis of lower genital tract inflammatory conditions.

PMID- 14678204
TI  - Intracellular expression of interleukin-4 and interferon-gamma by a Mycobacterium
      tuberculosis antigen-stimulated CD4+ CD57+ T-cell subpopulation with memory
      phenotype in tuberculosis patients.
AB  - In some chronic pathological conditions, antigen persistence activates and
      expands the CD4+ CD57+ T-cell subset. The host immune response against
      tuberculosis infection is maintained through the continuous presence of antigen
      stimulated effector/memory helper T cells. To determine whether CD4+ CD57+ T
      cells were also expanded in human tuberculosis, we analysed (by flow cytometry)
      the phenotype of peripheral blood CD4+ T cells from 30 tuberculosis patients and
      30 healthy controls. We observed a significant increase in the CD4+ CD57+ T-cell
      subset in tuberculosis patients in comparison to healthy controls (P < 0.001).
      Most CD4+ CD57+ T cells exhibited a CD28- CD45RO+ CD62L- phenotype, which is
      associated with memory cells. In vitro, a higher number of antigen-stimulated
      CD4+ CD57+ T cells produced intracellular interferon-gamma and interleukin-4
      compared with antigen-stimulated CD4+ CD57- T cells (P < 0.001). These findings
      suggest that the majority of CD4+ CD57+ T cells correspond to a phenotype of
      activated memory T cells.

PMID- 14678205
TI  - Highly up-regulated CXCR3 expression on eosinophils in mice infected with
      Schistosoma japonicum.
AB  - CXCR3, predominately expressed on memory/activated T cells, is a receptor for
      both interferon-gamma inducible protein-10/CXC ligand 10 (CXCL10) and monokine
      induced by interferon-gamma/CXCL9. We reported here that CXCR3 was highly up
      regulated on infiltrating eosinophils in Schistosoma japonicum egg-induced
      granuloma in the mouse liver. It was also highly and functionally up-regulated on
      peritoneal exudate eosinophils in mice infected with S. japonicum. The phenomena
      were demonstrated at protein and mRNA levels using immunohisto- and
      immunocytochemistry evaluation of biopsy, flow cytometry and real-time
      quantitative reverse transcriptase-polymerase chain reaction technique, and
      verified by Northern blotting and chemotaxis assay in vitro. We also found that
      CCR3 expression on the infiltrating and peritoneal exudate cells was
      significantly decreased, CXCR4 expression was unchanged during the 42-day period
      of infection. We screened mRNA expression levels of the all known chemokine
      receptors in purified peritoneal exudate eosinophils and liver granuloma
      dominated by eosinophils. CXCR3 was highly and functionally up-regulated on
      peritoneal exudate eosinophils in mice infected with S. japonicum, meanwhile CCR3
      was significantly and functionally down-regulated in these cells. The findings
      could lead to a better understanding of the chemokine receptor expression pattern
      of eosinophils at inflamed tissue sites caused by parasites. These could be also
      crucial for establishing a therapeutic strategy for eosinophilic inflammation via
      intervention in chemokine actions.

PMID- 14678207
TI  - Nonanoic acid--an experimental irritant.
AB  - Irritant contact dermatitis is defined as a non-immunological skin reaction
      following exposure to various chemical, mechanical and physical factors. It is
      known that the skin response to irritants depends on the irritant applied and
      differs between chemically different irritants. Sodium lauryl sulfate (SLS) is an
      anionic detergent and the most frequently used substance in experimental irritant
      contact dermatitis. In 1980, it was suggested that nonanoic acid (NNA) could be
      used as a positive control when patch testing. Since then, NNA has been used as
      an experimental irritant in several studies and has been used as a chemically
      different substance compared to SLS. The present article presents a review of the
      application of NNA in studies on skin irritancy and experimental irritant contact
      dermatitis.

PMID- 14678206
TI  - Nerve fibres are required to evoke a contact sensitivity response in mice.
AB  - Previous work has indicated that the dermis and epidermis of skin contains
      abundant nerve fibres closely associated with Langerhans' cells. We have
      investigated whether these nerve endings are necessary for inducing and evoking a
      contact sensitivity (CS) response. Topical application of a general or a peptide
      (calcitonin gene-related peptide and substance P)-specific neurotoxin was
      employed to destroy the nerve fibres at skin sites subsequently used to induce or
      evoke the CS response. Elimination of nerve fibres abolished both induction and
      effector stages of the specific CS response. Denervation did not destroy the
      local Langerhans' cells, which were observed in increased numbers, or prevent
      them from migrating to lymph nodes. The local CS response was also abolished by
      systemic deletion of capsaicin-sensitive nerve fibres, suggesting that the loss
      of response was not non-specific but associated with the loss of specific nerve
      fibres. The results indicate that peptidergic nerve fibres are required to elicit
      a CS response and may be vital to the normal function of the immune system.

PMID- 14678208
TI  - Experimental systemic contact dermatitis from nickel: a dose-response study.
AB  - Systemic contact dermatitis is usually seen as flare-up of previous dermatitis or
      de novo dermatitis similar to allergic contact dermatitis. Although systemic
      contact dermatitis from medicaments is a well-established entity, the existence
      of clinically relevant systemic reactions to oral nickel exposure, in particular
      systemic reactions to nickel in the daily diet, remains controversial. Several
      studies have shown that oral exposure to nickel can induce systemic contact
      dermatitis in nickel-sensitive individuals. In most of these studies, however,
      the exposure dose of nickel used has been considerably higher than the nickel
      content in the normal daily diet. The aim of the current investigation was to
      study dose-response dependency of oral exposure to nickel. In a double-blind,
      placebo-controlled oral exposure trial, 40 nickel-sensitive persons and 20
      healthy (non-nickel-sensitive) controls were given nickel sulfate hexahydrate in
      doses similar to and greater than the amount of nickel ingested in the normal
      Danish daily diet. The nickel content in urine and serum before and after oral
      exposure was measured to determine nickel uptake and excretion. The influence of
      the amount of nickel ingested on the clinical reactions to oral exposure and on
      nickel concentrations in serum and urine was evaluated. Among nickel-sensitive
      individuals, a definite dose-response dependency was seen, following oral
      exposure to nickel. 7 of 10 nickel-sensitive individuals had cutaneous reactions
      to oral exposure to 4.0 mg nickel, an amount approximately 10 times greater than
      the estimated normal daily dietary intake of nickel. 4 of 10 nickel-sensitive
      individuals had cutaneous reactions to 1.0 mg nickel, a dose which is close to
      the estimated maximum amount of nickel contained in the daily diet. 4 of 10
      nickel-sensitive individuals reacted to 0.3 mg nickel or to the amount equivalent
      to that contained in a normal daily diet, and 1 of 10 reacted to a placebo. None
      of the 20 healthy controls had cutaneous reactions to 4.0 mg nickel or to a
      placebo. Prior to oral exposure, there was no measurable difference in the amount
      of nickel in the urine or serum of nickel-sensitive persons and healthy controls.
      Following the oral challenge, the nickel content in the urine and serum of both
      nickel-sensitive and healthy control individuals was directly related to the dose
      of nickel ingested.

PMID- 14678209
TI  - A stronger patch test elicitation reaction to the allergen hydroxycitronellal
      plus the irritant sodium lauryl sulfate.
AB  - Household and cleaning products often contain both allergens and irritants. The
      aim of this double-blinded, randomized, paired study was to determine whether
      patch testing with an allergen (hydroxycitronellal) combined with an irritant
      [sodium lauryl sulfate (SLS)] cause a stronger patch test elicitation reaction
      than patch testing with the allergen (hydroxycitronellal) alone, in patients
      previously patch tested positive to hydroxycitronellal. A stronger patch test
      elicitation reaction was defined as at least 1 day of patch test reading showing
      more positive patch tests (+, ++ or +++) on the forearm patch tested with 6
      concentrations of SLS plus hydroxycitronellal than on the forearm tested with 6
      concentrations of hydroxycitronellal alone and no day of patch test readings
      showing more positive tests on the hydroxycitronellal forearm. 15/20 (75%) had at
      least 1 day of patch test reading with more positive patch tests on the forearm
      patch tested with SLS plus hydroxycitronellal and no day of patch test readings
      with more positive patch tests on the forearm tested with hydroxycitronellal (P =
      0.0253). Estimation of the blood flow with laser Doppler supported these
      findings.

PMID- 14678210
TI  - Quantitative risk assessment for the induction of allergic contact dermatitis:
      uncertainty factors for mucosal exposures.
AB  - The quantitative risk assessment (QRA) paradigm has been extended to evaluating
      the risk of induction of allergic contact dermatitis from consumer products.
      Sensitization QRA compares product-related, topical exposures to a safe
      benchmark, the sensitization reference dose. The latter is based on an
      experimentally or clinically determined 'no observable adverse effect level'
      (NOAEL) and further refined by incorporating 'sensitization uncertainty factors'
      (SUFs) that address variables not adequately reflected in the data from which the
      threshold NOAEL was derived. A critical area of uncertainty for the risk
      assessment of oral care or feminine hygiene products is the extrapolation from
      skin to mucosal exposures. Most sensitization data are derived from skin contact,
      but the permeability of vulvovaginal and oral mucosae is greater than that of
      keratinized skin. Consequently, the QRA for some personal products that are
      exposed to mucosal tissue may require the use of more conservative SUFs. This
      article reviews the scientific basis for SUFs applied to topical exposure to
      vulvovaginal and oral mucosae. We propose a 20-fold range in the default
      uncertainty factor used in the contact sensitization QRA when extrapolating from
      data derived from the skin to situations involving exposure to non-keratinized
      mucosal tissue.

PMID- 14678211
TI  - Use of the local lymph node assay in the evaluation of the sensitizing potential
      of pharmaceutical process intermediates.
AB  - The murine local lymph node assay (LLNA) has recently been developed to determine
      the contact sensitization potential of chemicals. Since its original development,
      the LLNA results have been the subject of extensive comparisons with guinea pig
      and human data. The investigations described here were designed to explore the
      ability of the LLNA to identify accurately, pharmaceutical process intermediates
      (PIs) known to cause contact allergy in humans. To that end, 16 PIs previously
      tested in the guinea-pig maximization test (GPMT) were tested in the LLNA.
      Another PI known to be a contact sensitizer in humans was tested only in the
      LLNA. Cases of contact sensitization in humans were reported only for PIs that
      were extreme sensitizers in the GPMT and had low EC3 values (concentration of the
      test substance required to generate a threefold increase in lymph node cell
      proliferation) in the LLNA. These data provide additional evidence that the LLNA
      is able to discriminate skin sensitizers from chemicals that do not possess a
      significant skin sensitization potential and is thus a useful method for hazard
      identification. In addition, this method also offers important animal welfare
      benefits and may also be useful for risk assessment purposes.

PMID- 14678212
TI  - Systemic acyclovir reaction subsequent to acyclovir contact allergy: which
      systemic antiviral drug should then be used?
AB  - Allergic contact dermatitis caused by acyclovir is rare. We report the 5th case
      of systemic acyclovir reaction subsequent to acyclovir contact dermatitis, with
      investigations made to determine an alternative antiviral treatment. A 23-year
      old woman, after dermatitis while using Zovirax cream, went on to develop
      urticaria after oral acyclovir. Patch tests were performed with the components of
      Zovirax cream (acyclovir, propylene glycol and sodium lauryl sulfate) and with
      other antiviral drugs. Patch tests were positive to Zovirax cream, acyclovir,
      valacyclovir and propylene glycol. Patch and prick tests with famciclovir were
      negative, but its oral administration caused an itchy erythematous dermatitis on
      the trunk and extremities. Our patient developed a systemic acyclovir reaction
      subsequent to acyclovir allergic contact dermatitis, with cross-reactions to
      valacyclovir and famciclovir. Their common chemical structure is the 2
      aminopurine nucleus. It is probably this part of the molecule that provokes both
      contact allergy and systemic reactions. The only antiviral drugs not having this
      core are foscarnet and cidofovir, and these could therefore be alternatives.

PMID- 14678214
TI  - Application of protective creams: use of a fluorescence-based training system
      decreases unprotected areas on the hands.

PMID- 14678213
TI  - Tolerance of fondaparinux in a patient allergic to heparins and other
      glycosaminoglycans.

PMID- 14678215
TI  - Localized aquagenic urticaria: efficacy of a barrier cream.

PMID- 14678216
TI  - Hand dermatitis in a student caused by Basic Red 46.

PMID- 14678217
TI  - Chromate: still an important occupational allergen for men in the UK.

PMID- 14678218
TI  - Occupational contact dermatitis, with asthma and rhinitis, from camomile in a
      cosmetician also with contact urticaria from both camomile and lime flowers.

PMID- 14678219
TI  - Contact urticaria due to nitrile gloves.

PMID- 14678220
TI  - Allergic contact stomatitis from paraformaldehyde and copal in a dental root
      canal filling.

PMID- 14678221
TI  - Lymphadenosis benigna cutis induced by iatrogenic contact dermatitis from
      dinitrochlorobenzene.

PMID- 14678222
TI  - Occupational allergic contact urticaria and asthma from diphenylmethane-4,4'
      diisocyanatae.

PMID- 14678223
TI  - Occupational contact dermatitis and contact urticaria in veterinarians.

PMID- 14678224
TI  - Very-low-voltage electrical injuries caused by cellular-phone chargers.

PMID- 14678225
TI  - Airborne occupational allergic contact dermatitis from N,N-bis[2-bromo-ethyl]
      aniline and N,N-bis [2-[(methylsulfonyl)-oxy ]ethyl]aniline in a chemistry
      student.

PMID- 14678226
TI  - Allergic contact dermatitis from polyethylene glycol monomethyl ether 350 in
      Solaraze gel.

PMID- 14678227
TI  - An isotopic response to patch testing.

PMID- 14678228
TI  - Occupational contact dermatitis caused by a personal-computer mouse mat.

PMID- 14678229
TI  - Role of angiotensin AT1 and AT2 receptors in cardiac hypertrophy and cardiac
      remodelling.
AB  - 1. Left ventricular hypertrophy (LVH) is an independent cardiovascular risk
      factor. Angiotensin AT1 receptor antagonism has been considered as a specific
      approach to block the renin-angiotensin system and been demonstrated to be able
      to prevent or regress LVH by interfering with the remodelling process of the
      heart. 2. Angiotensin AT1 receptor blockade induces a marked increase in
      angiotensin (Ang) II, which may stimulate the AT2 receptors. Gene expression of
      AT1 and AT2 receptors increases in a time-dependent manner in cardiac remodelling
      following myocardial infarction. 3. Considerable efforts have been made to
      clarify the role of AT2 receptors in cardiac hypertrophy and remodelling since
      the mid-1990s, resulting in controversial reports: the AT2 receptor mediates
      actions either opposite to or in coordination with those of the AT1 receptor.
      Moreover, there are many reports of no significant effects mediated by AT2
      receptors. 4. Based on the studies reviewed in the present article, we assume
      that the predominant effect of AngII in cardiac hypertrophy and cardiac
      remodelling is growth promoting and that this effect is mediated mainly via AT1
      receptors. The AT2 receptors may affect the hypertrophic process by interacting
      with other cardiac membrane proteins, enzymes and autacoids. Before coming to a
      conclusion as to whether AT2 receptor stimulation or antagonism is beneficial to
      the heart, more studies should be performed in different LVH models, especially
      long-term treatment protocols in vivo.

PMID- 14678230
TI  - Phytosterol additives increase blood pressure and promote stroke onset in salt
      loaded stroke-prone spontaneously hypertensive rats.
AB  - 1. To assess the effect of dietary phytosterol on stroke and the lifespan of salt
      loaded stroke-prone spontaneously hypertensive rats (SHRSP), we investigated the
      effects of the addition of phytosterol to soybean oil (phytosterol content: 0.3%)
      on stroke onset, lifespan following onset of stroke and overall lifespan compared
      with canola oil (phytosterol content: 0.9%). 2. Six-week-old male SHRSP were fed
      a test diet prepared by the addition of canola oil (CA diet), soybean oil (SO
      diet), soybean oil plus 0.6% phytosterol (SO + 0.06P diet) or soybean oil plus
      4.5% phytosterol (SO + 0.45P diet) as a 10% fat source. 3. Systolic blood
      pressure (SBP) increased in the SO + 0.06P and SO + 0.45P groups compared with
      the SO group and the increase was dependent on the amount of phytosterol added,
      indicating that the addition of phytosterol to soybean oil may promote an
      increase in SBP in salt-loaded SHRSP. 4. The onset of stroke was shortest in the
      SO + 0.45P group and survival after the onset of stroke was shortest in the CA
      group. Consequently, the SO + 0.45P and CA groups showed marked lifespan
      shortening, indicating that a fivefold greater amount of phytosterol was required
      to produce an effect equivalent to that of canola oil. 5. Investigation of the
      mRNA expression of ATP-binding cassette (ABC) transporters involved in intestinal
      phytosterol absorption indicated significant decreases in the intestinal mRNA
      expression of Abcg5 and Abcg8 in SHRSP and Wistar-Kyoto rats compared with Wistar
      rats. 6. In conclusion, the addition of phytosterol to soybean oil elevated SBP
      and promoted the onset of stroke, which may cause a reduction in survival time.
      However, a fivefold greater amount of phytosterol was required to produce an
      effect that was equivalent to the survival time-shortening effect of canola oil.
      The significant decrease in the intestinal mRNA expression of Abcg5 and Abcg8 in
      SHRSP may be responsible, at least in part, for the unfavourable effects observed
      following the addition of phytosterol.

PMID- 14678231
TI  - Morphological evidence of reinnervation of the baroreceptive regions in
      sinoaortic-denervated rats.
AB  - 1. The arterial baroreflex (ABR) plays an important role in the maintenance of
      the stability of blood pressure. Sinoaortic denervation (SAD) destroys the
      integrity of the reflex arc and produces severe organ damage in rats. However,
      partial recovery of ABR function has been observed following chronic denervation.
      The aim of the present study was to determine whether there was morphological
      evidence of reinnervation of the aortic arch and carotid sinus following SAD. 2.
      A substantial body of physiological and morphological evidence suggests that
      substance P (SP) may be a neurotransmitter contained in first-order sensory
      baroreceptor afferents; therefore, the patterns of vascular SP and neurofilament
      (NF) immunoreactive (IR) innervation of the aortic arch and carotid sinus were
      investigated in the present study. 3. Ten-week-old male Sprague-Dawley rats
      underwent SAD or sham operation. Whole mounts of carotid bifurcation and aortic
      arch were prepared for immunohistochemical study at various time points (1, 9 and
      16 weeks after operation). 4. The results of computerized image analysis show
      that the mean density of NF- and SP-IR nerves of SAD rats 9 and 16 weeks after
      operation increased gradually and significantly compared with that of rats 1 week
      after operation. 5. In conclusion, the results indicate that there is
      reinnervation of the aortic arch and carotid sinus by NF- and SP-IR fibres in SAD
      rats, which may be the morphological basis for the partial restoration of ABR
      function over time after SAD.

PMID- 14678232
TI  - Cosegregation analysis of natriuretic peptide genes and blood pressure in the
      spontaneously hypertensive rat.
AB  - 1. The natriuretic peptide precursor A (Nppa) and B (Nppb) genes are candidate
      genes for hypertension and cardiac hypertrophy in the spontaneously hypertensive
      rat (SHR). The purpose of the present study was to determine the role of the Nppa
      and Nppb genes in the development of hypertension in the SHR. 2. A cohort (n =
      162) of F2 segregating intercross animals was established between strains of
      hypertensive SHR and normotensive Wistar-Kyoto rats. Blood pressure and heart
      weight were measured in each rat at 12-16 weeks of age. Rats were genotyped using
      11 informative microsatellite markers, distributed in the vicinity of the Nppa
      marker on rat chromosome 5 including an Nppb marker. The phenotype values were
      compared with genotype using the computer package mapmaker 3.0 (Whitehead
      Institute, Boston, MA, USA) to determine whether there was a link between the
      genetic variants of the natriuretic peptide family and blood pressure or cardiac
      hypertrophy. 3. A strong correlation was observed between the Nppa marker and
      blood pressure. A quantitative trait locus (QTL) for blood pressure on chromosome
      5 was identified between the Nppa locus and the D5Mgh15 marker, less than 2 cM
      from the Nppa locus. The linkage score for the blood pressure QTL on chromosome 5
      was 3.8 and the QTL accounted for 43% of the total variance of systolic blood
      pressure, 54% of diastolic blood pressure and 59% of mean blood pressure. No
      association was found between the Nppb gene and blood pressure. This is the first
      report of linkage between the Nppa marker and blood pressure in the rat. There
      was no correlation between the Nppa or Nppb genes or other markers in this region
      and either heart weight or left ventricular weight in F2 rats. 4. These findings
      suggest the existence of a blood pressure-dependent Nppa marker variant or a gene
      close to Nppa predisposing to spontaneous hypertension in the rat. It provides a
      strong foundation for further detailed genetic studies in congenic strains, which
      may help to narrow down the location of this gene and lead to positional cloning.

PMID- 14678233
TI  - Cellular mechanism of pituitary adenylate cyclase-activating polypeptide-induced
      atrial tachyarrhythmia in canine isolated arterially perfused right atria.
AB  - 1. Pituitary adenylate cyclase-activating polypeptide (PACAP) induces atrial
      tachyarrhythmia (AT). However, the cellular mechanism responsible for this
      remains unclear. 2. In six canine isolated arterially perfused right atria, high
      resolution optical mapping techniques were used to measure action potentials
      during control conditions and after PACAP injection (1 nmol). 3. During steady
      state pacing at a cycle length of 300 msec, the action potential duration was
      shorter during PACAP than during control (P < 0.001). In addition, maximum
      repolarization gradients during PACAP (4 +/- 1 msec/mm) were similar to those
      during control (5 +/- 1 msec/mm; n = 6). Transmural repolarization gradients were
      also similar between the two groups. 4. After PACAP, AT was easily initiated with
      a single premature extrastimulus and was associated with a focal pattern of
      activation. However, AT was not initiated by a single premature stimulus during
      control. 5. In conclusion, the PACAP-induced AT is associated with a focal
      pattern of activation that is independent of local repolarization gradients.
      These data suggest that increased dispersion of repolarization is not necessarily
      required for the induction of AT.

PMID- 14678234
TI  - Cyclic GMP protein kinase activity is reduced in thyroxine-induced hypertrophic
      cardiac myocytes.
AB  - 1. We tested the hypothesis that the cGMP-dependent protein kinase has major
      negative functional effects in cardiac myocytes and that the importance of this
      pathway is reduced in thyroxine (T4; 0.5 mg/kg per day for 16 days) hypertrophic
      myocytes. 2. Using isolated ventricular myocytes from control (n = 7) and T4
      treated (n = 9) rabbit hypertrophic hearts, myocyte shortening was studied with a
      video edge detector. Oxygen consumption was measured using O2 electrodes. Protein
      phosphorylation was measured autoradiographically. 3. Data were collected
      following treatment with: (i) 8-(4-chlorophenylthio)guanosine-3',5'-monophosphate
      (PCPT; 10-7 or 10-5 mol/L); (ii) 8-bromo-cAMP (10-5 mol/L) followed by PCPT;
      (iii) beta-phenyl-1,N2-etheno-8-bromoguanosine-3',5'-monophosphorothioate, SP
      isomer (SP; 10-7 or 10-5 mol/L); or (iv) 8-bromo-cAMP (10-5 mol/L) followed by
      SP. 4. There were no significant differences between groups in baseline
      percentage shortening (Pcs; 4.9 +/- 0.2 vs 5.6 +/- 0.4% for control and T4
      groups, respectively) and maximal rate of shortening (Rs; 64.8 +/- 5.9 vs 79.9 +/
      7.1 micro m/ s for control and T4 groups, respectively). Both SP and PCPT
      decreased Pcs (-43 vs-21% for control and T4 groups, respectively) and Rs (-36 vs
      22% for control and T4 groups, respectively), but the effect was significantly
      reduced in T4 myocytes. 8-Bromo-cAMP similarly increased Pcs (28 vs 23% for
      control and T4 groups, respectively) and Rs (20 vs 19% for control and T4 groups,
      respectively). After 8-bromo-cAMP, SP and PCPT decreased Pcs (-34%) and Rs (-29%)
      less in the control group. However, the effects of these drugs were not altered
      in T4 myocytes (Pcs -24%; Rs -22%). Both PCPT and cAMP phosphorylated the same
      five protein bands. In T4 myocytes, these five bands were enhanced less. 5. We
      conclude that, in control ventricular myocytes, the cGMP-dependent protein kinase
      exerted major negative functional effects but, in T4-induced hypertrophic
      myocytes, the importance of this pathway was reduced and the interaction between
      cAMP and the cGMP protein kinase was diminished.

PMID- 14678235
TI  - Vascular non-endothelial nitric oxide induced by swimming exercise stress in
      rats.
AB  - 1. Herein, we report the effects of acute or chronic forced swimming on vascular
      responsiveness to angiotensin (Ang) II. 2. The possible involvement of locally
      produced substances, such as nitric oxide (NO) and prostanoids, in these effects
      were studied in rat thoracic aorta and superior mesenteric arteries. 3. Chronic,
      but not acute, swimming reduced the efficacy (maximal effect; Emax) of AngII in
      thoracic aorta and mesenteric arteries, either with intact or denuded
      endothelium. 4. The efficacy of AngII was reduced in the presence of indomethacin
      in mesenteric arteries, but not in the aorta, from either control or chronically
      stressed rats. 5. Treatment with NG-monomethyl-l-arginine reversed the effect of
      chronic stress on the response to AngII, suggesting that chronic stress may
      increase non-endothelial NO activity in both the aorta and mesenteric arteries.
      6. The effects of acute and chronic stress on vascular reactivity were selective
      for AngII because no changes were observed on the effects of phenylephrine.

PMID- 14678236
TI  - Direct vascular effects of HR780, a novel 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitor.
AB  - 1. We have examined the effects of HR780, a novel 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitor, on porcine endothelial cell (EC) injury
      induced by xanthine (X)/xanthine oxidase (XO), a source of superoxide anion.
      Furthermore, the effects of HR780 on platelet-derived growth factor (PDGF)
      induced migration and fetal calf serum (FCS)-induced proliferation of rabbit
      smooth muscle cells (SMC) were investigated. 2. Probucol, at 10 micro mol/L,
      significantly (P < 0.001) and completely suppressed lactate dehydrogenase leakage
      induced by X/XO. At 10 micro mol/L, HR780 significantly (P = 0.010) inhibited
      X/XO-induced EC injury. 3. HR780 dose-dependently inhibited PDGF-induced SMC
      migration and FCS-induced SMC proliferation. The addition of mevalonate
      completely abolished the inhibitory effect of HR780 on SMC proliferation. Another
      HMG-CoA reductase inhibitor, simvastatin (0.1-100 micro mol/L), also inhibited
      the migration and proliferation responses as potently as HR780. In contrast,
      pravastatin (0.1-100 micro mol/L) did not show any effects. 4. This in vitro
      study provides the first evidence that HR780 protects the vascular endothelium
      from oxidant stress and inhibits the migration and proliferation of SMC.

PMID- 14678237
TI  - Effect of salt and water intake on epithelial sodium channel mRNA abundance in
      the kidney of salt-sensitive Sabra rats.
AB  - 1. The level of mRNA expression of epithelial sodium channel (ENaC) subunits was
      studied in a salt-dependent hypertensive rat strain (Sabra). These rats exhibit
      high vasopressin levels compared with their normotensive counterparts. We also
      investigated whether this expression is influenced by changes in the sodium
      intake/aldosterone axis or in the fluid intake/vasopressin axis. 2. A higher
      expression of beta- and gamma-subunit mRNA was found in salt-sensitive compared
      with salt-resistant rats on a normal salt diet. A high-sodium diet did not alter
      mRNA abundance in either substrain. In contrast, water supplementation in salt
      sensitive rats fed the high-sodium diet induced a marked reduction in mRNA
      abundance of beta- and gamma-subunits. 3. The present study provides evidence
      that beta- and gamma-subunits of ENaC are differently expressed in the kidney of
      salt-sensitive and salt-resistant Sabra rats and that their abundance is
      regulated by vasopressin, not by sodium intake. These results are consistent with
      the hypothesis that increased vasopressin-dependent ENaC expression and activity
      may contribute to the pathogenesis of hypertension in salt-sensitive Sabra rats.

PMID- 14678238
TI  - Analgesic duration and kinetics of liposomal bupivacaine after subcutaneous
      injection in mice.
AB  - 1. The objective of the present study was to assess the time-course profile of
      analgesia and bupivacaine concentrations at the site of injection after
      subcutaneous administration of a single dose of standard bupivacaine or a novel
      controlled-release liposomal bupivacaine formulation. 2. Groups of mice were
      injected subcutaneously with 0.2 mL of 0.5% standard bupivacaine or 0.5, 1 or 2%
      liposomal bupivacaine. 3. A prolonged duration of analgesia occurred in mice
      receiving liposomal bupivacaine. In the liposomal groups, the bupivacaine
      remained at the injection site for more than 96 h, compared with approximately 8
      h in groups injected with standard bupivacaine. 4. These results confirm that the
      prolonged analgesia observed after injection of the liposomal formulation is
      associated with sustained higher levels of bupivacaine at the site of injection.

PMID- 14678241
TI  - Effects of calcitriol on the immune system: new possibilities in the treatment of
      glomerulonephritis.
AB  - 1. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the hormonal form of vitamin D, is
      widely appreciated to play a central role in calcium and phosphate homeostasis.
      However, it is becoming increasingly clear that the sterol also play an important
      role in the regulation of cellular growth, haematopoietic tissues and the immune
      system, as well as in the modulation of hormone secretion by several endocrine
      glands. 2. In the present review, some of the mechanisms by which 1,25(OH)2D3
      regulates immune function are highlighted. Moreover, a number of studies on the
      effects of calcitriol in several experimental animal models of renal disease are
      reported, suggesting new possibilities in the therapy of glomerulonephritis.

PMID- 14678242
TI  - Lipoxygenase and cyclo-oxygenase products in the control of regional kidney blood
      flow in rabbits.
AB  - 1. The aim of the present study was to examine the roles of cyclo-oxygenase (COX)
      and lipoxygenase (LOX)-dependent arachidonate signalling cascades in the control
      of regional kidney blood flow. 2. In pentobarbitone-anaesthetized rabbits treated
      with NG-nitro-l-arginine and glyceryl trinitrate to 'clamp' nitric oxide, we
      determined the effects of ibuprofen (a COX inhibitor) and esculetin (a LOX
      inhibitor) on resting systemic and renal haemodynamics and responses to renal
      arterial infusions of vasoconstrictors. 3. Ibuprofen increased mean arterial
      pressure (14 +/- 5%) and reduced medullary laser Doppler flux (MLDF; 26 +/- 6%)
      when administered with esculetin. A similar pattern of responses was observed
      when ibuprofen was given alone, although the reduction in MLDF was not
      statistically significant. Esculetin tended to increase renal blood flow (RBF; 16
      +/- 7%) and MLDF (28 +/- 13%) when given alone, but not when combined with
      ibuprofen. 4. After vehicle, renal arterial infusions of noradrenaline,
      angiotensin II and endothelin-1 reduced RBF and cortical laser Doppler flux
      (CLDF), but not MLDF. In contrast, renal arterial [Phe2,Ile3,Orn8]-vasopressin
      reduced MLDF but not RBF or CLDF. Ibuprofen alone did not significantly affect
      these responses. Esculetin, when given alone, but not when combined with
      ibuprofen, enhanced noradrenaline-induced renal vasoconstriction. In contrast,
      esculetin did not significantly affect responses to [Phe2,Ile3,Orn8]-vasopressin,
      angiotensin II or endothelin-1. 5. We conclude that COX products contribute to
      the maintenance of arterial pressure and renal medullary perfusion under 'nitric
      oxide clamp' conditions, but not to renal haemodynamic responses to the
      vasoconstrictors we tested. Lipoxygenase products may blunt noradrenaline-induced
      vasoconstriction, but our observations may, instead, reflect LOX-independent
      effects of esculetin.

PMID- 14678244
TI  - Effects of losartan on pressure overload-induced cardiac gene expression
      profiling in rats.
AB  - 1. In the present study, the effects of losartan on myocardial gene expression
      changes following cardiac hypertrophy were investigated. 2. Male Wistar rats were
      randomized to receive 5 or 30 mg/kg per day losartan (i.p.) 1 day after
      suprarenal abdominal aortic constriction. Two weeks later, cardiac morphology and
      function were recorded with echocardiography and mean arterial central pressure
      was measured using carotid catheters. Myocardial gene expression was assessed
      with cDNA microarrays. 3. The ratios of left ventricular weights to bodyweights,
      the posterior thickness of the left ventricle and mean arterial central pressure
      were significantly increased by aortic constriction and attenuated by losartan in
      a dose-related manner. Genes in different functional categories were regulated in
      pressure overload-induced cardiac hypertrophy and the majority of changes in gene
      expression were inhibited by losartan in a dose-dependent manner. 4. However,
      there were still some genes that were unaffected by losartan, even at a higher
      dose. In contrast, losartan, especially at a lower dose, was able to induce
      changes in the expression of several additional genes that were unregulated in
      simple aortic constriction. 5. In conclusion, losartan is able to inhibit
      pressure overload-induced cardiac hypertrophy, as well as the majority of
      pressure overload-related changes in gene expression. The genes that remained
      unaffected or those that were additionally induced by losartan are likely to be
      new targets for investigation or therapy.

PMID- 14678245
TI  - Science and physicianly practice: are they compatible?
AB  - 1. Science, in the present paper, is defined as the systematic study of humans,
      based on deduction and inferences from reproducible observation and measurement.
      Physicianly practice is the art of healing through accurate diagnosis and
      treatment. 2. The science that is conducted by clinical pharmacologists involves
      both clinical studies, which is working with patients or normal volunteers, and a
      variety of in vitro techniques. 3. Studies of patients with exercise-induced
      asthma (EIA) suggest that inhaled beta-adrenoceptor agonists may afford
      protection against EIA by inhibiting mast cell mediator release. In vitro
      experiments with human lung tissue demonstrate dose-dependent inhibition of
      histamine and leukotriene release by fenoterol, a beta-adrenoceptor agonist. 4.
      Studies in normal volunteers following the inhalation of corticosteroids
      (fluticasone and budesonide), which are used for the treatment of asthma,
      detected the presence of the administered drugs in the plasma. The potency ratio
      of fluticasone : budesonide for inhibition of the hypothalamic-pituitary-adrenal
      (HPA) axis in these normal volunteers was similar to the potency ratio determined
      in animal models of inflammation. 5. Studies in vitro showed that fluticasone and
      budesonide have effects on alkaline phosphatase release from human osteoblasts,
      with a potency ratio of similar rank order to that observed in vivo on the HPA
      axis. 6. These studies have shown that in vivo and in vitro techniques can be
      used in a complementary fashion to address questions of clinical relevance.

PMID- 14678243
TI  - Effect of cross-fostering on blood pressure and renal function in the New Zealand
      genetically hypertensive rat.
AB  - 1. The severity of hypertension displayed by adult spontaneously hypertensive
      rats (SHR) and Dahl (SS/Jr) rats can be reduced by 20-30 mmHg if the hypertensive
      pup is cross-fostered to a normotensive mother within the first 2 weeks of birth.
      In the SHR, at least, this blood pressure-lowering effect arises through
      programming of the neonatal kidney to excrete sodium more effectively. Thus,
      cross-fostering may only be effective in lowering pressure in salt-sensitive
      hypertensive strains. Accordingly, the aim of the present study was to determine
      whether cross-fostering is effective in lowering adult blood pressure in the salt
      resistant New Zealand genetically hypertensive (GH) rat. 2. Genetically
      hypertensive and control normotensive (N) rat pups were reared by either their
      natural mothers or a foster mother of the opposite strain (NX and GHX). Blood
      pressure was tracked from the age of 6-18 weeks, at which time renal function was
      assessed using standard clearance techniques in anaesthetized rats. Renal
      function was also assessed in a separate group of young rats at 5-6 weeks of age.
      3. Cross-fostered GHX rats had lower blood pressure than GH rats, but this
      difference was only apparent until 9 weeks. The NX rats had higher blood
      pressures than N rats, but again pressure converged at 10 weeks. Basal renal
      function did not differ between GH and GHX rats or between N and NX rats at
      either age. However, young GH rats had lower renal blood flow, glomerular
      filtration rate, urine output and sodium excretion than N rats. 4. These data
      show that cross-fostering is effective in lowering blood pressure in GH rats,
      albeit transiently. The kidneys do not appear to play a role, because renal
      function did not differ under the current experimental conditions between GH and
      GHX rats. However, the kidney may play a greater role in the onset of
      hypertension in the GH rat than previously thought.

PMID- 14678246
TI  - In silico insights: chemical and structural characteristics associated with
      uridine diphosphate-glucuronosyltransferase substrate selectivity.
AB  - 1. Undesirable absorption, distribution, metabolism, excretion properties are the
      cause of many drug development failures and this has led to the need to identify
      such problems earlier in the development process. This work highlights
      computational (in silico) approaches used to identify characteristics influencing
      the metabolism of uridine diphosphate (UDP)-glucuronosyltransferase (UGT)
      substrates. Uridine diphosphate-glucuronosyltransferase facilitates conjugation
      between glucuronic acid and a nucleophilic site within a substrate and is one of
      the major drug-metabolizing enzymes. 2. An understanding of the relevant
      structural and chemical characteristics of the ligand and the enzyme active site
      will lead to greater utilization of metabolically relevant structural information
      in drug design. However, an X-ray crystal structure of UGT is not yet available,
      little has been reported about important structurally or catalytically relevant
      amino acids and only recently has the reported substrate profile of UGT isoforms
      reached an interpretable level. 3. A database of all the known substrates and non
      substrates for each human UGT isoform was assembled and a range of modelling
      approaches assessed. Currently, pharmacophore models developed using Catalyst
      (Accelrys, San Diego, CA, USA) indicate that substrates of the UGT1A family share
      two key hydrophobic regions 3 and 6-7 A from the site of glucuronidation in a
      well-defined spatial geometry. Furthermore, two-dimensional quantitative
      structure-activity relationship models show significant reliance on substrate
      lipophilicity and a range of other descriptors that are known to capture
      information relevant to ligand-protein interactions. 4. In conclusion, substrate
      based modelling of UGT appears both useful and feasible, with significant
      potential for determining aspects of chemical structure associated with
      metabolism and to quantify the nature of the relationship for UGT substrates. The
      development of a novel, user-defined 'glucuronidation feature' for alignment was
      crucial to the development of pharmacophore-based UGT models.

PMID- 14678247
TI  - Experimental therapeutics of Parkinson's disease.
AB  - 1. The loss of central dopamine, which characterises Parkinson's disease, led to
      the main pharmacological strategy for treatment, namely levodopa, a dopamine
      replacement therapy. Several years after treatment, the majority of patients
      experience dose-limiting side-effects and loss of symptom control. There is a
      resurgence of interest in neurosurgery for treating the Parkinson's disease,
      particularly in new techniques targeting the subthalamic nucleus (STN), which is
      overactive in Parkinson's disease and contributes to symptom development. 2. We
      performed unilateral subthalamotomy (lesioning the subthalamic nucleus via the
      toxin N-methyl-d-aspartate) in marmosets and rats with experimentally induced
      parkinsonism (induced using the toxin 6-hydroxydopamine). A range of similar
      behaviours common to both rodents and primates were evaluated before and after
      each type of surgery. Post-mortem histology was used to confirm the lesions. We
      also provide details of a case with Parkinson's disease who underwent high
      frequency bilateral stimulation of the STN and in whom we analysed the STN post
      mortem. 3. Unilateral subthalamotomy improved akinesia in parkinsonian primates.
      However, both monkeys and rodents showed postural abnormalities. The patient who
      underwent bilateral high-frequency stimulation showed improvement of akinesia and
      other disease symptoms and no postural abnormalities. Post-mortem analysis did
      not demonstrate substantial damage of the STN as a result of the electrodes. 4.
      Although unilateral subthalamotomy improves some aspects of parkinsonism, it
      causes postural abnormalities in animal models of Parkinson's disease. Because
      bilateral high-frequency STN stimulation improves disease symptoms, is reversible
      and is not reported to induce postural side-effects, it may be a better surgical
      therapy for Parkinson's disease than lesioning the STN.

PMID- 14678248
TI  - Oxidative metabolism of tamoxifen to Z-4-hydroxy-tamoxifen by cytochrome P450
      isoforms: an appraisal of in vitro studies.
AB  - 1. Tamoxifen is used for the prevention and treatment of oestrogen receptor
      positive breast cancer. 2. Tamoxifen is metabolized extensively and the formation
      of Z-4-hydroxy-tamoxifen (Z-4-OH-tam), a potent anti-oestrogen with high affinity
      for the oestrogen receptor, is believed to be strongly related to the therapeutic
      benefit achieved following tamoxifen treatment. 3. In vitro studies using human
      liver microsome preparations have shown considerable interindividual variability
      in the formation rates of Z-4-OH-tam. 4. Cytochrome P450 (CYP) isoform-specific
      chemical and monoclonal antibody inhibition studies have demonstrated that
      CYP2B6, CYP2C9, CYP2D6 and CYP3A4 all mediate the formation of Z-4-OH-tam. 5.
      Significant associations between the percentage inhibition of Z-4-OH-tam by CYP
      isoform-specific inhibitors and the rate of metabolism of CYP isoform-specific
      index reactions and between individual expression of CYP2B6, CYP2C9 and CYP2D6
      and Z-4-OH-tam formation rates indicate predominant roles for these isoforms in
      this pathway. 6. Genotyping of patients with regards to CYP2B6, CYP2C9 and CYP2D6
      may play a role in prediction of Z-4-OH-tam formation and, consequently, ultimate
      therapeutic benefit of tamoxifen treatment.

PMID- 14678249
TI  - Novel isoforms of NADPH oxidase in vascular physiology and pathophysiology.
AB  - 1. Vascular cells have evolved to use reactive oxygen species (ROS), such as
      superoxide and hydrogen peroxide, as signalling molecules. Under physiological
      conditions, ROS are important regulators of cell cycle, protein kinase activity
      and gene expression. However, in vascular disease states, such as hypertension
      and hypercholesterolaemia, excessive production of ROS may overwhelm the anti
      oxidant defence mechanisms of cells, resulting in 'oxidative stress', damage to
      the artery wall and, ultimately, development of atherosclerotic plaques. 2. The
      primary source of ROS in the vasculature is NADPH oxidase. There appear to be at
      least three isoforms of NADPH oxidase expressed in the vascular wall, each
      differing with respect to the flavin-containing catalytic subunit it uses to
      transfer electrons from NADPH to molecular oxygen. Thus, although endothelial
      cells and adventitial fibroblasts express a gp91phox-containing NADPH oxidase
      similar to that originally identified in phagocytes, vascular smooth muscle cells
      may rely on novel homologues of gp91phox, namely Nox1 and Nox4, to produce
      superoxide. 3. Controversy remains over which isoform(s) of NADPH oxidase is
      responsible for the oxidative stress associated with vascular diseases. We and
      others have shown that although gp91phox mRNA expression is upregulated during
      atherogenesis in human and animal models, expression of the Nox4 subunit remains
      unchanged. Nox1 expression is also likely to be increased in diseased arteries;
      however, its relative level of expression, at least at the mRNA level, appears to
      be markedly lower than that of the other gp91phox homologues, even after
      upregulation. 4. Whether these findings suggest that a gp91phox-containing NADPH
      oxidase is more important than either Nox4 or Nox1 in vascular disease awaits
      studies examining relative protein expression and enzyme kinetics of each
      subunit, as well as the effects of targeted gene deletion of each of these
      gp91phox homologues on atherogenesis.

PMID- 14678250
TI  - Cerebral vascular effects of reactive oxygen species: recent evidence for a role
      of NADPH-oxidase.
AB  - 1. Reactive oxygen species (ROS) are a diverse family of molecules that are
      produced throughout the vascular wall. Many ROS, such as the superoxide anion
      (*O2-) and hydrogen peroxide (H2O2), are now known to act as cellular signalling
      molecules within blood vessels. In particular, these molecules can exert powerful
      effects on vascular tone. 2. Cerebral arteries are relatively unusual in their
      responsiveness to ROS. Unlike in many systemic vessels, both *O2- and H2O2 can
      cause vasodilatation in the cerebral microcirculation. 3. Reactive oxygen species
      can be produced in the vasculature via a variety of mechanisms; however, it
      appears that the primary source of *O2- within blood vessels is the enzyme NADPH
      oxidase. 4. In cerebral vessels, activation of NADPH-oxidase causes both *O2-
      production and vasodilatation, indicating that NADPH-oxidase-derived ROS may have
      a functional role in the regulation of cerebral vascular tone. 5. Elevated levels
      of NADPH-oxidase activity and expression occur in cardiovascular disease states
      such as hypertension, atherosclerosis and subarachnoid haemorrhage. 6. Thus, ROS
      may contribute to the regulation of cerebral vascular tone during both
      physiological and pathological conditions.

PMID- 14678251
TI  - Redox-dependent signalling by angiotensin II and vascular remodelling in
      hypertension.
AB  - 1. Hypertension is associated with structural alterations of resistance arteries,
      a process known as remodelling (increased media-to-lumen ratio). 2. At the
      cellular level, vascular remodelling involves changes in vascular smooth muscle
      cell (VSMC) growth, cell migration, inflammation and fibrosis. These processes
      are mediated via multiple factors, of which angiotensin (Ang) II appears to be
      one of the most important in hypertension. 3. Angiotensin II signalling, via AT1
      receptors, is upregulated in VSMC from resistance arteries of hypertensive
      patients and rats. This is associated with hyperactivation of vascular NADPH
      oxidase, leading to increased generation of reactive oxygen species (ROS),
      particularly O2- and H2O2. 4. Reactive oxygen species function as important
      intracellular second messengers to activate many downstream signalling molecules,
      such as mitogen-activated protein kinase, protein tyrosine phosphatases, protein
      tyrosine kinases and transcription factors. Activation of these signalling
      cascades leads to VSMC growth and migration, modulation of endothelial function,
      expression of pro-inflammatory mediators and modification of extracellular
      matrix. 5. Furthermore, ROS increase intracellular free Ca2+ concentration
      ([Ca2+]i), a major determinant of vascular reactivity. 6. All these processes
      play major roles in vascular injury associated with hypertension. Accordingly,
      ROS and the signalling pathways that they modulate provide new targets to regress
      vascular remodelling, reduce peripheral resistance and prevent hypertensive end
      organ damage. 7. In the present review, we discuss the role of ROS as second
      messengers in AngII signalling and focus on the implications of these events in
      the processes underlying vascular remodelling in hypertension.

PMID- 14678252
TI  - Mouse isolated perfused heart: characteristics and cautions.
AB  - 1. Owing to the considerable potential for manipulating the murine genome and, as
      a consequence, the increasing availability of genetically modified models of
      cardiovascular diseases, the mouse is fast becoming a cornerstone of animal
      research. However, progress in the use of various murine preparations is hampered
      by the lack of facilities and skills for the adequate physiological assessment of
      genetically modified mice. 2. We have attempted to address this problem by
      refining and characterizing a mouse isolated heart preparation that was
      originally developed for use with larger hearts. 3. We used the isolated buffer
      perfused Langendorff preparation (perfused at constant flow or constant pressure)
      to characterize: (i) the frequency-response characteristics; (ii) heart isolation
      conditions; (iii) perfusion chamber conditions; (iv) temperature-function
      relationships; (v) stability over extended periods of perfusion; (vi) perfusate
      calcium-function relationships; (vii) pressure-volume relationships; (viii)
      pressure-rate relationships; and (ix) flow-function relationships.

PMID- 14678253
TI  - Responses to ischaemia and reperfusion in the mouse isolated perfused heart and
      the phenomenon of 'contractile cycling'.
AB  - 1. The aims of the present study were to examine the response of the murine heart
      to ischaemia and reperfusion and to determine whether these responses are
      influenced by the strain of mouse. 2. Isolated, paced (600 b.p.m.) murine (T/O
      mice) hearts were perfused aerobically (2.6 mL/min) with buffer for 40 min before
      being subjected to whole-heart (global) ischaemia (37 degrees C) for 20, 30, 35,
      40 or 50 min prior to 90 min reperfusion. Contracture was measured during
      ischaemia and the reperfusate was collected and assayed for creatine kinase. 3.
      With increasing durations of ischaemia, there was a progressive decline in
      postischaemic recovery such that left ventricular developed pressure (LVDP) after
      20, 30, 35, 40 or 50 min ischaemia was 75 +/- 4, 65 +/- 4, 38 +/- 6, 18 +/- 2 and
      18 +/- 2% of pre-ischaemic controls, respectively. 4. There was a reciprocal
      increase in creatine kinase leakage, indicative of a time-dependent increase in
      tissue injury. 5. To compare the ischaemic vulnerability of different strains,
      hearts from Swiss and C57BL/6 mice were perfused for 20 min, followed by 40 min
      global ischaemia (37 degrees C) and 60 min reperfusion. Functional recovery of
      LVDP in Swiss mouse hearts was significantly higher than in C57BL/6 mouse hearts
      (39 +/- 7 vs 20 +/- 4%, respectively; P < 0.04, t-test; 10 d.f.). 6. During our
      investigations, we encountered and characterized the phenomenon of 'contractile
      cycling' (cyclical patterns of declining and increasing left ventricular systolic
      pressure of variable severity and duration). 7. We have shown that this
      confounding phenomenon is a manifestation of an underlying metabolic disturbance
      of unknown origin that can be attenuated by the addition of substrates, such as
      pyruvate or acetate, to the standard glucose-containing perfusion buffer.

PMID- 14678254
TI  - Neurocardiovascular regulation in mice: experimental approaches and novel
      findings.
AB  - 1. Neural mechanisms are of major importance in the regulation of arterial blood
      pressure, blood volume and other aspects of cardiovascular function. The recent
      explosion in gene discovery and advances in molecular technologies now provide
      the opportunity to define the molecular and cellular mechanisms essential to
      integrative neurocardiovascular regulation. The unique susceptibility of mice to
      genetic manipulation makes this species an attractive model for such
      investigation. 2. We provide here a brief overview of: (i) experimental
      approaches used to assess autonomic and reflex control of the circulation in
      mice; (ii) novel mechanisms of neurocardiovascular regulation revealed using
      these approaches; and (iii) findings from recent studies involving mouse models
      of cardiovascular disease.

PMID- 14678255
TI  - Activin and TR3 orphan receptor: two 'atheroprotective' genes as evidenced in
      dedicated mouse models.
AB  - 1. Atherosclerosis is a multifactorial, inflammatory disease of the arterial
      vessel wall that is promoted by various well-defined risk factors. Although
      numerous genes, expressed in different vascular and inflammatory cells, have been
      implicated in this disease, it is widely appreciated that most of the genes and
      gene products vital for initiation and progression of atherosclerosis are
      unknown. 2. We follow two strategies in an attempt to make up for the void of
      essential knowledge. First, we study candidate genes that have not been implied
      in human atherosclerosis before, notably the differentiation factor activin A. 3.
      Second, we performed a genome-wide search by differential display reverse
      transcription-polymerase chain reaction. This study indicated potential
      involvement of the TR3 orphan receptor transcription factor in smooth muscle cell
      (SMC) (patho)physiology. 4. To reveal functional involvement of these proteins in
      SMC during atherosclerosis, we performed experiments with mouse models, adjusted
      either to the characteristics of a secreted protein or to that of an
      intracellular transcription factor. 5. The secreted protein activin A was studied
      in mice infected systemically with recombinant adenoviral vehicles, resulting in
      predominant hepatic expression and subsequent high protein levels in the
      circulation. 6. To study the role of TR3 in atherosclerosis, we generated
      transgenic mice in which promoter sequences were applied that direct expression
      of the transgenes to SMC of the arterial tree. 7. Two approaches were taken to
      induce the formation of SMC-rich lesions: (i) activation of femoral artery SMC by
      placement of a loosely fitting cuff; and (ii) ligation of the carotid artery. 8.
      The aim of the present review is to illustrate the different approaches that can
      be taken to assess the potential relevance of genes in atherosclerosis in
      carefully selected mouse models. 9. Based on the results described, we propose
      that both activin A and TR3 prevent excessive SMC proliferation.

PMID- 14678256
TI  - Stem cell-derived angiogenic/vasculogenic cells: possible therapies for tissue
      repair and tissue engineering.
AB  - 1. The recent ability to isolate stem cells and study their specific capacity of
      self-renewal with the formation of different cell types has opened up exciting
      vistas to help the repair of damaged tissue and even the formation of new tissue.
      In the present review, we deal with the characteristics and sources that stem
      cells can be derived and cultured from. 2. We focus on the role that stem cell
      derived vascular cells or endothelial progenitor cells (EPC) may play in
      (re)vascularization of ischaemic and engineered tissues. This so-called
      vasculogenesis resembles the embryological process in which 'haemangioblasts'
      differentiate in blood cells, as well as in primitive vessels. Although also
      derived from the blood-forming bone marrow, in adult life vasculogenic stem cells
      contribute only little to the regular vascular repair mechanisms: namely (i)
      angiogenesis (outgrowth of vessels from existing vessels); and (ii)
      arteriogenesis (monocyte-aided increase in the calibre of existing arteriolar
      collaterals). 3. Most attempts to increase vascular repair by stem cells involve
      the use of growth factors, which mobilize stem cells from bone marrow into the
      blood, sometimes combined with isolation and reinfusion of these cells after ex
      vivo expansion and differentiation into EPC. 4. Clear improved perfusion of
      ischaemic sites and new vasculature has been observed in vivo mostly in animal
      models. Specific homing or administration of these cells and regulated and
      quantitative expansion and (final) differentiation at these vascular (repair)
      sites are less studied, but are paramount for efficacy and safety. 5. In
      conclusion, the use of embryonic stem cells will still encounter ethical
      objections. Moreover, special attention and measures are needed to cope with the
      allogeneic barriers that these cells usually encounter. In general, the long and
      complicated ex vivo cultures to obtain sufficient offspring from the very small
      numbers of stem cells that can be obtained as starting material will be costly
      and cumbersome. Both basic research on conceptual matters and cost-effective
      development of the product itself will have to go a long way before the clinical
      use of some volume can be expected.

PMID- 14678258
TI  - Host genetics and the dissection of mycobacterial immunity.

PMID- 14678257
TI  - Immunopathogenic mechanisms in psoriasis.
AB  - Psoriasis is a common autoimmune skin disease characterized by T cell-mediated
      hyperproliferation of keratinocytes. The disease has a strong but complex genetic
      background with a concordance of approximately 60% in monozygotic twins, and
      recent linkage and high resolution association studies indicate that HLA-Cw*0602
      is itself a major susceptibility allele for psoriasis. Patients carrying this
      allele have been shown to have different clinical features and earlier age of
      disease onset, and patients homozygous for this allele have about 2.5 times
      higher disease risk than heterozygotes. Published data indicate that CD8+ T cells
      may play a major effector role in psoriasis. Epidermal infiltration of
      predominantly oligoclonal CD8+ T cells, and probably also of CD4+ T cells in the
      dermis, is a striking feature of chronic psoriasis lesions, indicating that these
      cells are responding to specific antigens. We argue that CD4+ T cells are
      essential for initiating and maintaining the pathogenic process of psoriasis but
      that cross-primed CD8+ T cells are the main effector cells responding to antigens
      in the HLA-Cw*0602 binding pocket of keratinocytes. It is further proposed that
      CD8+ T cells are involved in the control of the Th1 polarization, which is
      observed in psoriasis lesions, through a complex interplay between CD4+, CD8+ T
      cells and cross-presenting dendritic cells. It is also suggested that spontaneous
      remissions or fluctuations in disease activity may be determined by a balance
      within the lesions between effector and suppressor CD4+ and CD8+ T cells.

PMID- 14678259
TI  - IgE-dependent enhancement of Th2 cell-mediated allergic inflammation in the
      airways.
AB  - T helper 2 (Th2) cell-derived cytokines, including interleukin (IL)-4, IL-5 and
      IL-13, play important roles in causing allergic airway inflammation. In contrast
      to Th2 cells, however, the role of IgE and mast cells in inducing allergic airway
      inflammation is not understood fully. In the present study, we addressed this
      point using transgenic mice expressing trinitrophenyl (TNP)-specific IgE (TNP-IgE
      mice), which enable us to investigate the role of IgE without the influence of
      antigen-specific T cell activation and other immunoglobulins. When the
      corresponding antigen, TNP-BSA, was administered intranasally to TNP-IgE mice, a
      large number of CD4+ T cells were recruited into the airways. In contrast, TNP
      BSA administration did not induce eosinophil recruitment into the airways or
      airway hyperreactivity. Furthermore, when ovalbumin (OVA)-specific Th2 cells were
      transferred to TNP-IgE mice and the mice were challenged with inhaled OVA, TNP
      BSA administration increased OVA-specific T cell recruitment and then enhanced
      Th2 cell-mediated eosinophil recruitment into the airways. These results indicate
      that IgE-induced mast cell activation principally induces CD4+ T cell recruitment
      into the airways and thus plays an important role in enhancing Th2 cell-mediated
      eosinophilic airway inflammation by recruiting Th2 cells into the site of
      allergic inflammation.

PMID- 14678260
TI  - Lung cell responses to M. tuberculosis in genetically susceptible and resistant
      mice following intratracheal challenge.
AB  - One approach to study the role of distinct cellular mechanisms in
      susceptibility/resistance to tuberculosis (TB) is to compare parameters of
      response to infection in the lungs of mouse strains exhibiting genetically
      determined differences in TB susceptibility/severity. Interstrain differences in
      antimycobacterial macrophage reactions, T cell responses & inflammation in the
      lungs of TB-susceptible I/St, TB-resistant A/Sn and (I/St x A/Sn)F1 mice were
      analysed following intratracheal inoculation of 103 CFUs of M. tuberculosis
      H37Rv. The antimycobacterial responses in the lungs of susceptible I/St mice were
      characterized by: (i) increased inflammatory infiltration by all major immune
      cell subsets; (ii) decreased type 1 cytokine production; (iii) impaired
      antimycobacterial activity of lung macrophages; (iv) unusually high proliferation
      of lung T lymphocytes. Differences in several parameters of anti-TB immunity
      between susceptible and resistant mice corresponded well to the polygenic pattern
      of TB control previously established in this mouse model. Importantly, lung
      macrophages isolated from noninfected mice were unable to respond to IFN-gamma by
      increasing their mycobactericidal function, but between weeks 3 and 5 of the
      infection this capacity developed in all mice. However, by this time point
      susceptible but not resistant mice demonstrated a pronounced decrease in IFN
      gamma production by lung cells. This chain of events may explain the inability of
      I/St mice to control both early and chronic TB infection.

PMID- 14678261
TI  - CTLA-4 blockade inhibits induction of Helicobacter pylori-associated gastritis in
      mice.
AB  - The balance between Th1 and Th2 response determines the outcome of Helicobacter
      pylori infection. Interferon (IFN)-gamma plays an inductive role in gastric
      inflammation, whereas interleukin (IL)-4 counterbalances Th1 response and
      suppresses the development of gastritis. Th cell response is regulated by co
      stimulatory factors. A co-stimulatory molecule, cytotoxic T lymphocyte-associated
      antigen-4 (CTLA-4), plays an inhibitory role in IL-2-dependent cell growth and
      mediates an optimal inhibitory signal to Th1 and Th2 cells. We administered anti
      CTLA-4 monoclonal antibody (MoAb), which blocks CTLA-4 signalling, to examine the
      relative role for this signalling during maturation of Th1 and Th2 cells in H.
      pylori infection in mice. Mice treated by anti-CTLA-4 MoAb within the first week
      of infection showed an inhibition of gastric inflammation, accompanied by an
      increasing ratio of H. pylori-specific IgG1/IgG2a in serum following infection.
      Furthermore, the treatment resulted in the higher ratio of IL-4/IFN-gamma by
      splenocytes in response to H. pylori antigen at 6 weeks after infection, compared
      with untreated mice. These results suggest that the predominance of Th2 response
      by CTLA-4 blockade leads to an inhibition of the development of gastric
      inflammation. CTLA-4 signalling could contribute to the regulation of Th subsets
      and the development of gastric inflammation in H. pylori infection.

PMID- 14678262
TI  - Graves' hyperthyroidism and thyroiditis in HLA-DRB1*0301 (DR3) transgenic mice
      after immunization with thyrotropin receptor DNA.
AB  - Familial and twin studies in Caucasians have established that the MHC class II
      allele HLA-DRB1*0301 (DR3) is a strong susceptibility gene in Graves'
      hyperthyroid disease (GD). To determine if a DR3 transgene could help establish
      an animal model for GD, we expressed DR3 molecules in class II-knockout NOD mice
      (H2Ag7-). DR3+g7- mice were given cardiotoxin prior to immunization on weeks 0, 3
      and 6 with plasmid DNA encoding human thyrotropin receptor (TSHR). Two groups of
      mice were also coimmunized with plasmid DNA for IL-4 or GM-CSF. Serial bleeds on
      weeks 8, 11 and 14 showed that approximately 20% of mice produced thyroid
      stimulating antibodies (Abs), and approximately 25% had elevated T4 levels. In
      particular, a subset displayed both signs of hyperthyroidism, resulting in
      approximately 30% with some aspect of GD syndrome. Additional mice had thyroid
      stimulating blocking Abs and/or TSH-binding inhibitory immunoglobulins, while
      most mice showed strong labelling of TSHR+ cells by flow cytometry.
      Interestingly, lymphocytic infiltration with thyroid damage and Abs to mouse
      thyroglobulin were also noted. Vector controls were uniformly negative. Thus, DR3
      transgenic mice can serve as a model for GD, similar to our earlier reports that
      this allele is permissive for the Hashimoto's thyroiditis model induced with
      human thyroglobulin.

PMID- 14678263
TI  - Anti-C1q autoantibodies in murine lupus nephritis.
AB  - Autoantibodies against C1q can be found in the circulation of patients with
      several autoimmune diseases including systemic lupus erythematosus (SLE). In SLE
      there is an association between the occurrence of these antibodies and renal
      involvement. How anti-C1q autoantibodies contribute to renal disease is currently
      unknown. Cohorts of MRL-lpr mice, which are known to develop age-dependent SLE
      like disease, were used to study the relationship between levels of anti-C1q
      autoantibodies and renal disease. We collected serum, urine and renal tissue and
      analysed autoantibodies, complement levels and renal deposition as well as renal
      function. At 2 months of age all mice already had elevated levels of anti-C1q
      autoantibodies, and elution of kidneys revealed the presence of these antibodies
      in renal immune deposits in MRL-lpr mice and not in control MRL+/+ mice. In
      conclusion, anti-C1q antibodies are already present in serum and immune deposits
      of the kidney early in life and therefore can play a role in nephritis during
      experimental SLE-like disease in mice.

PMID- 14678264
TI  - The cardioprotector dexrazoxane augments therapeutic efficacy of mitoxantrone in
      experimental autoimmune encephalomyelitis.
AB  - The present study investigates the immunological effects of a combination
      treatment of mitoxantrone and the cardioprotector dexrazoxane in experimental
      autoimmune encephalomyelitis (EAE). Mitoxantrone, an anthracycline-derived
      immunosuppressive drug has been approved recently for treatment of very active
      multiple sclerosis (MS). Its prolonged use is limited due to its cardiotoxic
      properties. Dexrazoxane (DZR (S)-(+)-1,2-bis (3,5.dioxopiperazinyl)propane, ICRF
      187) is an iron III chelator which in animal models and in cancer patients
      reduces anthracycline and mitoxantrone induced cardiotoxicity when given
      immediately before these agents. We examined the immunological effects of
      dexrazoxane in combination with mitoxantrone in experimental autoimmune
      encephalomyelitis (EAE) in Lewis rats. EAE was induced by active immunization
      with myelin basic protein (MBP) or by adoptive transfer of MBP specific T cells
      (AT-EAE). The clinical course, spinal cord pathology, activity of
      metalloproteinases (MMP-2 and MMP-9) and T cell apoptosis were assessed.
      Monotherapy with DZR ameliorated slightly the course of actively induced EAE and
      AT-EAE. The combination of DZR and mitoxantrone was superior to mitoxantrone
      given alone. Clinical amelioration ran in parallel with the marked reduction of
      inflammatory infiltration which was nearly abolished by the combination
      treatment. DZR did not affect the activity of metalloproteinase 9 and did not
      increase the proportion of apoptotic lymph node cells ex vivo or T cells in situ.
      We conclude that in addition to its cardioprotective role, DZR augments
      mitoxantrone-mediated immunosuppressive effects in animal models of human central
      nervous system (CNS) autoimmune disease. Clinical trials in MS patients are
      warranted to evaluate the unexpected immunosuppressive efficacy of DZR as add-on
      treatment.

PMID- 14678265
TI  - Age-related bias in function of natural killer T cells and granulocytes after
      stress: reciprocal association of steroid hormones and sympathetic nerves.
AB  - Stress-associated immune responses were compared between young (8 weeks of age)
      and old (56 weeks) mice. Since stress suppresses the conventional immune system
      (i.e. T and B cells) but inversely activates the primordial immune system (i.e.
      extrathymic T cells, NKT cells, and granulocytes), these parameters were analysed
      after restraint stress for 24 h. The thymus became atrophic as a function of age,
      and an age-related increase in the number of lymphocytes was seen in the liver.
      Although the number of lymphocytes in both the thymus and liver decreased as the
      result of stress, the magnitude was much more prominent in the thymus. To
      determine stress-resistant lymphocyte subsets, two-colour immunofluorescence
      tests were conducted in the liver and spleen. NKT cells were found to be such
      cells in the liver of young mice. On the other hand, an infiltration of
      granulocytes due to stress was more prominent in the liver of old mice than in
      young mice. Liver injury as a result of stress was prominent in young mice. This
      age-related bias in the function of NKT cells and granulocytes seemed to be
      associated with a difference in the responses of catecholamines (high in old
      mice) and corticosterone (high in young mice) after stress. Indeed, an injection
      of adrenaline mainly induced the infiltration of granulocytes while that of
      cortisol activated NKT cells. The present results suggest the existence of age
      related bias in the function of NKT cells and granulocytes after stress and that
      such bias might be produced by different responses of sympathetic nerves and
      steroid hormones between young and old mice.

PMID- 14678267
TI  - Modulation of antigen presentation by autoreactive B cell clones specific for
      GAD65 from a type I diabetic patient.
AB  - We used a GAD65-specific human B-T cell line cognate system in vitro to
      investigate the modulation of GAD65 presentation by autoantibody, assessed in a
      proliferation assay. Generally, if the T cell determinant overlaps or resides
      within the antibody epitope, effects of presentation are blunted while if they
      are distant can lead to potent presentation. For three different autoreactive B-T
      cell line cognate pairs, the modulation of GAD65 presentation followed the mode
      of overlapping or distant epitopes with resultant potent or undetectable
      presentation. However, other cognate pairs elicited variability in this pattern
      of presentation. Notably, one B cell line, DPC, whose antibody epitope did not
      overlap with the T cell determinants, was consistently poor in presenting GAD65.
      Using the fluorescent dye Alexa Fluor 647 conjugated to GAD65 to study receptor
      mediated antigen endocytosis showed that all the antigen-specific B cell clones
      were efficient in intracellular accumulation of the antigen. Additionally,
      multicolour immunofluorescence microscopy showed that the internalized
      GAD65/surface IgG complexes were rapidly targeted to a perinuclear compartment in
      all GAD-specific B cell clones. This analysis also demonstrated that HLA-DM
      expression was reduced strongly in DPC compared to the stimulatory B cell clones.
      Thus the capability of antigen-specific B cells to capture and present antigen to
      human T cell lines is dependent on the spatial relationship of B and T cell
      epitopes as well other factors which contribute to the efficiency of
      presentation.

PMID- 14678266
TI  - Molecular mechanisms of interleukin-10-mediated inhibition of NF-kappaB activity:
      a role for p50.
AB  - Nuclear factor kappa B (NF-kappaB) is a transcription factor pivotal for the
      development of inflammation. A dysregulation of NF-kappaB has been shown to play
      an important role in many chronic inflammatory diseases including rheumatoid
      arthritis, inflammatory bowel disease and psoriasis. Although classical NF
      kappaB, a heterodimer composed of the p50 and p65 subunits, has been well
      studied, little is known about gene regulation by other hetero- and homodimeric
      forms of NF-kappaB. While p65 possesses a transactivation domain, p50 does not.
      Indeed, p50/p50 homodimers have been shown to inhibit transcriptional activity.
      We have recently shown that Interleukin-10 exerts its anti-inflammatory activity
      in part through the inhibition of NF-kappaB by blocking IkappaB kinase activity
      and by inhibiting NF-kappaB already found in the nucleus. Since the inhibition of
      nuclear NF-kappaB could not be explained by an increase of nuclear IkappaB, we
      sought to further investigate the mechanisms involved in the inhibition of NF
      kappaB by IL-10. We show here that IL-10 selectively induced nuclear
      translocation and DNA-binding of p50/p50 homodimers in human monocytic cells. TNF
      alpha treatment led to a strong translocation of p65 and p50, whereas
      pretreatment with IL-10 followed by TNF-alpha blocked p65 translocation but did
      not alter the strong translocation of p50. Furthermore, macrophages of p105/p50
      deficient mice exhibited a significantly decreased constitutive production of MIP
      2alpha and IL-6 in comparison to wild type controls. Surprisingly, IL-10
      inhibited high constitutive levels of these cytokines in wt macrophages but not
      in p105/p50 deficient cells. Our findings suggest that the selective induction of
      nuclear translocation and DNA-binding of the repressive p50/p50 homodimer is an
      important anti-inflammatory mechanism utilized by IL-10 to repress inflammatory
      gene transcription.

PMID- 14678268
TI  - High-level endothelial E-selectin (CD62E) cell adhesion molecule expression by a
      lipopolysaccharide-deficient strain of Neisseria meningitidis despite poor
      activation of NF-kappaB transcription factor.
AB  - Binding of host inflammatory cells to the endothelium is a critical contributor
      to the vascular damage characteristic of severe meningococcal disease and is
      regulated by endothelial cell adhesion molecules such as ICAM-1, VCAM-1 and
      CD62E. Intact meningococci induce far higher levels of CD62E than
      lipopolysaccharide (LPS) alone, whereas LPS is at least as potent as meningococci
      at inducing both VCAM-1 and ICAM-1 expression. This suggests that meningococci
      possess additional factors other than LPS present in whole bacteria that result
      in differential adhesion molecule expression. To investigate this possibility, we
      studied the capacity of an LPS-deficient isogenic strain of serogroup B Neisseria
      meningitidis H44/76 (lpxA-) to induce endothelial cell adhesion molecule
      expression and translocation of the transcription factor NF-kappaB, and compared
      it to both parent and unencapsulated strains of both B1940 and H44/76 and
      purified LPS. Although the LPS-deficient isogenic mutant of strain H44/76 was
      found to be a poor inducer of NF-kappaB, it induced higher levels of CD62E
      expression than LPS alone. These data provide evidence that intact meningococci
      induce a range of signals in the endothelium that are distinct from those seen
      with purified LPS alone and that they occur in a LPS-dependent and LPS
      independent manner. These signals may explain the potent effects of N.
      meningitidis on CD62E expression on vascular endothelium and provide a basis for
      the complex endothelial dysregulation seen in meningococcal sepsis.

PMID- 14678269
TI  - Evidence for autoantibody-induced CD4 depletion mediated by apoptotic and non
      apoptotic mechanisms in HIV-positive long-term surviving haemophilia patients.
AB  - It is believed that autoimmune phenomena and apoptosis contribute to CD4
      depletion. We investigated 11 long-term (>20 years) HIV-infected haemophilia
      patients and 10 healthy controls. Using four-colour-fluorescence flow cytometry,
      we studied the proportions of CD3+CD4+ and CD3+CD4- blood lymphocytes that were
      CD95+, CD95L+, immune complex+ (IC+, consisting of IgM, IgG, C3d and/or gp120),
      and were viable or non-viable (propidium iodide+ = PI+). In addition, we studied
      viability of CD4+IgG+ patient lymphocytes using the apoptosis marker annexin and
      the permeability indicator 7-amino actinomycin D (7-AAD). HIV+ patients had a
      higher proportion of CD3+CD4+IgG+PI+ lymphocytes than healthy controls (median:
      3.7%versus 0.3%; P = 0.00001). These non-viable IgG-coated lymphocytes might have
      been killed in vivo by ADCC or complement lysis; 9.1% of the circulating CD3+CD4+
      blood lymphocytes were IgG+PI- (controls: 2.5%; P = 0.001). These viable IgG
      coated lymphocytes might be targets for phagocytosis or anti-CD95 autoantibody
      mediated apoptosis. Because HIV+ patients and healthy controls had similar
      proportions of PI+ or PI- CD3+CD4+ lymphocytes that carried CD95L on the surface,
      and because CD3+CD4+CD95L+ cells that were IgG+, C3d+ and/or gp120- were
      increased in HIV+ patients, the role of CD95L-induced apoptosis in long-term HIV
      infected haemophilia patients remains unclear. The findings that HIV+ patients
      had higher proportions of CD3+CD4+CD95+ (PI+: 6.5%versus 1.4%; P = 0.00002; PI-:
      55.8%versus 44.4%; P = 0.04) blood lymphocytes and that the proportion of
      CD4+IgG+Annexin+7-AAD- blood lymphocytes was associated inversely with peripheral
      CD4 counts (r = -0.636; P < 0.05) suggest that attachment of IgG to CD4+ blood
      lymphocytes (anti-CD95?) induces in some lymphocytes apoptosis with subsequent
      depletion of these IgG-coated apoptotic CD4+ lymphocytes from the circulation. We
      found supporting evidence for the contention that autoantibody-induced apoptotic
      and non-apoptotic mechanisms contribute to CD4 depletion in long-term HIV
      infected haemophilia patients.

PMID- 14678270
TI  - NK cells modulate the cytotoxic activity generated by Mycobacterium leprae-hsp65
      in leprosy patients: role of IL-18 and IL-13.
AB  - Protection against intracellular pathogens such as Mycobacterium leprae is
      critically dependent on the function of NK cells at early stages of the immune
      response and on Th1 cells at later stages. In the present report we evaluated the
      role of IL-18 and IL-13, two cytokines that can influence NK cell activity, in
      the generation of M. leprae-derived hsp65-cytotoxic T lymphocytes (CTL) from
      peripheral blood mononuclear cells (PBMC) of leprosy patients. We demonstrated
      that IL-18 modulates hsp65-induced CTL generation and collaborates with IL-12 for
      this effect. In paucibacillary (PB) patients and normal controls (N) depletion of
      NK cells reduces the cytolytic activity. Under these conditions, IL-12 cannot up
      regulate this CTL generation, while, in contrast, IL-18 increases the cytotoxic
      activity both in the presence or absence of NK cells. IL-13 down-regulates the
      hsp65-induced CTL generation and counteracts the positive effect of IL-18. The
      negative effect of IL-13 is observed in the early stages of the response,
      suggesting that this cytokine affects IFNgamma production by NK cells. mRNA
      coding for IFNgamma is induced by IL-18 and reduced in the presence of IL-13,
      when PBMC from N or PB patients are stimulated with hsp65. Neutralization of IL
      13 in PBMC from multibacillary (MB) leprosy patients induces the production of
      IFNgamma protein by lymphocytes. A modulatory role on the generation of hsp65
      induced CTL is demonstrated for IL-18 and IL-13 and this effect takes place
      through the production of IFNgamma.

PMID- 14678271
TI  - Nicotinamide does not influence cytokines or exhaled NO in human experimental
      endotoxaemia.
AB  - This study examined the hypothesis that nicotinamide could attenuate endotoxin
      induced inflammatory responses in humans as indicated by levels of cytokines and
      nitric oxide. Ten healthy male volunteers participated in a randomised, double
      blind, cross-over design with regard to the effects of nicotinamide. The
      volunteers received orally 4 g nicotinamide or placebo at 14 h and at 2 h
      preceding the experiment (total dose of 8 g). Endotoxin (E. coli, 2 ng/kg), was
      administered intravenously. Blood samples and haemodynamic data were collected
      prior to and up to 6 h after the endotoxin infusion. Orally exhaled NO was
      measured hourly. Following endotoxin, body temperature increased from baseline
      36.3 +/- 0.09 degrees C to a maximum of 38.0 +/- 0.1 degrees C for all (mean +/-
      SEM, P < 0.001) and heart rate increased from 59 +/- 1.9 to 87.0 +/- 2.6
      beats/min after 3 h (mean +/- SEM, P < 0.001). Endotoxin challenge also markedly
      elevated the TNF-alpha, IL-6, IL-8 and IL-10 concentrations (P < 0.001 versus
      baseline for all) during the study period. Orally exhaled NO also increased (P <
      0.01) compared to baseline. Nicotinamide treatment did not influence the patterns
      of cytokine and NO response to endotoxin. In conclusion, there was no effect on
      the inflammatory parameters by oral nicotinamide at a dose of 8 g, limiting the
      potential use of this agent for anti-inflammatory purpose in man.

PMID- 14678272
TI  - Mushroom plant workers experience a shift towards a T helper type 2 dominant
      state: contribution of innate immunity to spore antigen.
AB  - Contemporary mushroom factories are places where there is a substantial risk of
      the occurrence of respiratory allergy. The aims of this investigation were to
      estimate its causative agents and to evaluate the contribution of innate immune
      response in mushroom workers who cultivate Hypsizigus marmoreus (Bunashimeji).
      Cross-sectional and follow-up studies were performed in the factory. We
      investigated CD1b, CD3, CD4, CD8, CD14, CD45RO, CD62L and CD161 expression in
      peripheral blood mononuclear cells (PBMC) by flow cytometry, and serum levels of
      interleukin (IL-2), IL-4, granulocyte-macrophage colony stimulating factor (GM
      CSF), IL-13 and interferon (IFN)-gamma by enzyme-linked immunosorbent assay
      (ELISA). Co-culture experiments of PBMC with spore extracts were also performed.
      Percentages of CD1b+ monocytes, natural killer (NK), NK T and CD4+ T cells were
      increased in the workers compared with controls. Increases in Th2 type cells,
      Th2/Th1 ratio and serum IL-13 and decreased IFN-gamma were detected, indicating a
      Th2-biased status of the workers. The follow-up study showed that monocytes and
      NK cells increased soon after employment while CD4+ T, Th2 and NK T cells
      increased gradually as employment time lengthened. Serum precipitating antibody
      to the mushroom antigen could be detected at a later stage. Co-cultivation of
      PBMC with the spore extracts induced much higher CD1b expression, and suppressed
      secretion of Th1 cytokine in culture supernatants. These results indicate that
      the mushroom antigen contains highly immunogenic substances which stimulate PBMC
      into a Th2-biased in vivo status, and innate immune cells might also play a
      critical role in developing respiratory allergy in mushroom workers.

PMID- 14678273
TI  - Multiple leucocyte activation markers to detect neonatal infection.
AB  - Diagnosis of congenital or neonatal infection is often based on clinical signs.
      However, clinical symptoms of infections may not be specific, and for this reason
      early diagnosis is often determined on results of laboratory tests, which may not
      currently be adequate. A more reliable method of detection of infection may be
      the demonstration of activated lymphocytes, which can be conducted rapidly and
      before the isolation of the infected organism. We have shown that detection of up
      regulation of CD45RO, an activated/memory isoform of CD45 present on T cells,
      provides a reasonably sensitive screening test for neonatal infection. We also
      showed that dual expression of CD45RA/CD45RO was up-regulated early during the
      infective process in neonates with documented infection. However, other
      leucocytes are also activated during the infective process. To improve the
      sensitivity of the neonatal infection screening test and to identify the types of
      leucocytes involved in the immune response to the infective organism, we studied
      further the up-regulation of a comprehensive range of surface activation markers
      on T cells, monocytes and natural killer (NK) cells from a group of 17 newborn
      patients with positive culture, a group of 40 possibly infected patients based on
      clinical signs and a control group. 'Normal' ranges were established for each
      activation marker for each leucocyte subset from 1 to 7 and 7-14-day-old newborns
      <35 weeks' gestation and 35-40 weeks' gestation. There was a significant increase
      in the percentage of T cells expressing CD25 in the peripheral blood from infants
      at 2 weeks of age. Expression of HLA-DR on T cells, CD25 and CD69 on monocytes
      and HLA-DR on NK cells was also increased significantly in the peripheral blood
      from infants at 2 weeks of age and may reflect a maturation of these functional
      surface molecules. Up-regulation of CD69 on NK cells was the most sensitive
      marker for neonatal sepsis (positive in 13/16 patients). CD69 and CD25 expression
      was increased significantly on T cells in 11/17 and 10/17 patients, respectively.
      A combination of CD45RA/CD45RO and CD45RO identified 11/16 infected patients.
      Measurement of CD69 expression on NK cells with CD45RA, CD45RO, CD25 and CD69
      expression on T cells resulted in a significant increase in at least two
      leucocyte activation markers from infected patients. In conclusion, this is the
      first report of the up-regulation of CD69 on NK cells as a sensitive marker of
      neonatal infection. A combination of this marker with CD45RA, CD45RO, CD25 and
      CD69 expression on peripheral blood derived T cells is the most sensitive and
      specific for neonatal infection.

PMID- 14678274
TI  - Immature anti-inflammatory response in neonates.
AB  - The inflammatory response plays a major role in the induction of several neonatal
      diseases. We hypothesize that an imbalance between the pro- and anti-inflammatory
      response is crucial for the previously shown enhanced production of
      proinflammatory cytokines in term and preterm infants during infection. To test
      this hypothesis, we compared the capacity to produce the main anti-inflammatory
      cytokines IL-10 and TGF-beta in term infants, preterm infants and adults at
      different levels of synthesis by quantitative real time reverse-transcribed PCR,
      flow cytometry, as well as enzyme-linked immunoassay. Term and preterm infants
      showed a profoundly diminished IL-10 mRNA-expression and IL-10 production after
      stimulation. In addition, the amount of TGF-beta-positive lymphocytes was
      significantly less in neonates than adults. Furthermore, there was a considerably
      lower inhibition of production of IL-1alpha, IL-6, IL-8 and TNF-alpha by the use
      of recombinant IL-10 in term and preterm infants compared with adults. These
      results demonstrate not only a diminished anti-inflammatory capacity but also a
      reduced response to anti-inflammatory stimuli in term and preterm infants. From
      these data we conclude that neonates display an immature compensatory anti
      inflammatory response syndrome (CARS) which may predispose preterm infants to
      harmful effects of proinflammatory cytokines resulting in severe organ sequelae
      during infection.

PMID- 14678275
TI  - Quantitative and functional characteristics of intestinal-homing memory T cells:
      analysis of Crohn's disease patients and healthy controls.
AB  - Circulating memory T cells can be subdivided on the basis of beta7 integrin
      expression. The beta7+ population contains cells primed in the intestine capable
      of homing back to the gut. We hypothesized that cytokine production by beta7+
      memory T cells reflects the specialized mucosal compartment in which they were
      primed. Flow cytometry of whole blood was used to assess numbers of beta7+
      (beta7hi and beta7int) and beta7- memory T cells and their production of Th1 and
      regulatory cytokines in healthy controls and Crohn's disease patients. In
      controls, beta7+ and beta7- memory T cells displayed a similar qualitative
      profile of cytokine production but the beta7+ population was enriched for
      cytokine-producing effector cells. In addition, the beta7hi population contained
      more cytokine-producing cells than the beta7int population, suggesting a gradient
      of cytokine production based on beta7 integrin expression. In active Crohn's
      disease, there was altered expression of beta7 integrin with a decrease in
      intestinal-homing memory T cells and an increase in systemic memory T cells.
      Furthermore, there was a selective loss of IL-10 and increase in TGF-beta in both
      beta7+ and beta7- memory T cell subsets which may contribute to the pathogenesis
      of the inflammatory process in Crohn's disease.

PMID- 14678276
TI  - Tumour necrosis factor-alpha converting enzyme (TACE) activity in human colonic
      epithelial cells.
AB  - Tumour necrosis factor (TNF)-alpha converting enzyme (TACE) releases biologically
      active, soluble TNF-alpha from transmembrane pro-TNF-alpha and has attracted
      interest as a specific therapeutic target in inflammatory bowel disease (IBD).
      Strong immunoreactivity for TACE protein was demonstrated recently in human
      colonic epithelium, but the function is unknown. We investigated if human colonic
      epithelial cells express functional TACE activity and how TACE expression is
      regulated in response to cytokine stimulation. TACE and TNF-alpha mRNA and
      protein expression were measured in HT-29 and DLD-1 colonic epithelial cells by
      reverse-transcription polymerase chain reaction, western blotting or enzyme
      linked immunosorbent assay. Monocytic THP-1 cells served as positive control.
      Functional TACE activity was identified and quantified in detergent extracts of
      cell lines and freshly isolated colonocytes from 14 IBD patients and five
      controls by a hydrolysis assay using an oligopeptide spanning the cleavage site
      in pro-TNF-alpha. HT-29 and DLD-1 cells spontaneously expressed TACE mRNA and the
      active form of TACE protein at levels similar to those of monocytic cells.
      Functional TACE activity was demonstrated in all cell lines and in cells of
      controls or IBD patients irrespective of disease activity. TACE mRNA expression
      and functional activity remained unchanged in cell lines after stimulation with
      TNF-alpha despite clear induction of TNF-alpha mRNA expression and release of
      soluble TNF-alpha protein. The release of soluble TNF-alpha protein was almost
      completely abolished by CH4474, a synthetic TACE inhibitor. We conclude that
      functional TACE activity is constitutively expressed in human colonic epithelial
      cells and responsible for processing of the mature, soluble form of TNF-alpha in
      response to cytokine stimulation.

PMID- 14678277
TI  - 'True' antimitochondrial antibody-negative primary biliary cirrhosis, low
      sensitivity of the routine assays, or both?
AB  - Anti-mitochondrial antibody (AMA) is considered the serological hallmark of
      primary biliary cirrhosis (PBC), but may be missing in a proportion of these
      patients. We assessed sensitivity and specificity of the currently available
      techniques for AMA detection in a large series of PBC patients and controls, and
      analysed their clinical and immunological features according to the AMA status.
      By indirect immunofluorescence on rat tissue sections and HEp-2 cells, Western
      immunoblot with bovine submitochondrial particles, and two ELISAs with AMA
      specific recombinant proteins, we evaluated the presence of AMA in 127 PBC
      patients, 166 patients with type 1 autoimmune hepatitis and 100 with non
      alcoholic fatty liver disease. In PBC patients Western immunoblot detects AMA
      significantly more often than indirect immunofluorescence on HEp-2 cells
      (85%versus 72%, P = 0.02) or rodent tissue sections (71%, P = 0.01); both ELISAs
      are only slightly less sensitive than Western immunoblot (81% and 78%). Ten
      patients with non alcoholic fatty liver disease were AMA-positive by indirect
      immunofluorescence, but none recognized AMA-specific epitopes in Western
      immunoblot or in ELISAs. Twelve patients with type 1 autoimmune hepatitis were
      AMA-positive by indirect immunofluorescence, but only 6 (3.6%) reacted by Western
      immunoblot and ELISAs. Western immunoblot or ELISA should be regarded as first
      line assay for the detection of AMA. Up to 15% of PBC patients are consistently
      AMA-negative, yet they share the same clinical, biochemical and histological
      features of AMA-positive PBC. Detection of AMA in type 1 autoimmune hepatitis
      might identify a subset of patients at risk of developing a hepatitic/cholestatic
      syndrome.

PMID- 14678278
TI  - Antibodies to inner ear antigens in Meniere's disease.
AB  - Meniere's disease (MD) is an idiopathic inner ear disorder characterized by
      fluctuating hearing loss, episodic vertigo and tinnitus. Its aetiology is
      unknown, although there is growing evidence that autoimmunity may be involved in
      its development. Using the Western blot immunoassay, we examined the reactivity
      to bovine inner ear antigens of sera from a series of MD patients who had
      previously been extensively studied for the presence of antibodies to collagens
      and membrane proteins. Reactivity to inner ear antigens of molecular weight 44
      and 53 kD was found in 11/25 (44%) and 10/25 (40%) of the patients, respectively;
      both antigens were absent in the sera of healthy donors. It is still unclear
      whether the antibodies to 44 and 53 kD proteins play a role in the pathogenesis
      of MD or if they instead represent the result of inflammation and tissue
      destruction. Even if the latter is true, they may contribute to the perpetuation
      of the disease or play a role as a cofactor in association with other mechanisms.

PMID- 14678279
TI  - Epitope mapping of anti-PR3 antibodies using chimeric human/mouse PR3 recombinant
      proteins.
AB  - Autoantibodies against proteinase 3 (PR3) and myeloperoxidase (MPO) (ANCA = anti
      neutrophil cytoplasmic antibodies) are used as diagnostic tools for patients with
      small vessel vasculitis. ANCA are detected by different assays, but the
      correlation between the results of these assays is generally poor. The overall
      aim of the study was to provide a framework for the future development of new
      assays with an increased diagnostic yield. In order to express discrete epitopes
      of human PR3 (hPR3), the nonantigenic molecules murine PR3 (mPR3) and human
      leucocyte elastase (HLE) were used as a framework. We constructed recombinant
      chimeric vectors and were able to produce 6 hPR3/mPR3 proteins and 3 hPR3/HLE
      proteins. Anti-PR3 monoclonal antibodies differed in their binding pattern to the
      chimeras, but no distinct binding region could be identified for any monoclonal
      antibody. The recombinant hPR3/mPR3 were also tested in ELISA with sera from
      patients with Wegener's granulomatosis with renal involvement. The results show
      that patients have antibodies to different constructs, indicating that the
      patients vary in their antibody repertoire from the beginning of the disease, and
      that patients may have antibodies from a broad range of clones early in the
      course of the disease. Recombinant hPR3/mPR3 chimeric proteins have a potential
      to be used as antigens in future ANCA assays.

PMID- 14678281
TI  - The pathophysiology of polycystic ovary syndrome.

PMID- 14678280
TI  - Autoantibodies recognizing citrullinated rat filaggrin in an ELISA using
      citrullinated and non-citrullinated recombinant proteins as antigens are highly
      diagnostic for rheumatoid arthritis.
AB  - The objective of the study was to determine the diagnostic value for rheumatoid
      arthritis (RA) of anti-filaggrin autoantibodies (autoAb) recognizing
      citrullinated recombinant rat filaggrin (ACRF) in community cases of very early
      arthritis. To evaluate the diagnostic value of ACRF, were studied sera from
      patients with different classified rheumatic diseases and healthy subjects (group
      1, n= 422) and 314 community cases of very early arthritis (group 2) that were
      classified as RA (n = 176), non-RA (n = 63) and undifferentiated (n = 75)
      arthritides after 1 years of follow-up. ACRF were measured using a new ELISA,
      with results expressed as the difference between the OD value obtained on
      citrullinated minus that on noncitrullinated rat filaggrin (differential ACRF;
      dACRF). For both groups, rheumatoid factors (RF), anti-keratin autoAb (AKA) and
      anti-perinuclear factor (APF) were tested; for group 2, anti-CCP autoAb were also
      tested. Different reactivity patterns against citrullinated and noncitrullinated
      filaggrin were observed. Almost all sera reacting with citrullinated but not
      noncitrullinated filaggrin were from RA patients. Among RA and non-RA sera that
      recognized both forms of filaggrin, a positive result was obtained only with RA
      sera. For groups 1 and 2, dACRF sensitivity was 58.4% and 30.7%, and specificity
      for RA was 99.5% and 98.4%, respectively. In group 2, dACRF specificity for RA
      was better than that of RF (92.1%), APF (95.2%), AKA (96.8%) and anti-CCP
      (95.2%). dACRF positive predictive value was high (98.2) and close to that given
      by the concomitant positivity of RF and anti-CCP autoAb. Despite a high positive
      correlation between AKA, APF, anti-CCP and dACRF test results, they were
      complementary since some sera were positive for only one test. Thus, in a
      community setting, anti-citrullinated rat filaggrin reactivity detected by a new
      ELISA, whose originality is based on the difference between serum's reactivities
      on the citrullinated and native forms of filaggrin, had a higher diagnostic value
      for RA than other autoAb.

PMID- 14678282
TI  - Thyroid incidentaloma: the ignorant in pursuit of the impalpable.

PMID- 14678283
TI  - Ultrasonography-guided fine-needle aspiration of thyroid incidentaloma:
      correlation with pathological findings.
AB  - BACKGROUND: There are many reports that diagnostic accuracy of fine-needle
      aspiration (FNA) of thyroid is improved with ultrasound guidance, especially for
      impalpable nodules. Despite its general acceptance, routine use of ultrasound
      guided fine-needle aspiration (USGFNA) has been the source of much controversy
      due to the lack of large-scale studies and lack of data on the natural course of
      well-differentiated thyroid cancer of small size. OBJECTIVE: The aim of our study
      was to define the rate of malignancy in relatively large numbers of patients with
      incidentally detected impalpable thyroid nodules and to assess the extent of
      disease in patients with suspicious or malignant cytology on USGFNA of thyroid
      nodules by surgery. PATIENTS: We retrospectively reviewed the medical records of
      the 267 patients who underwent USGFNA of incidental thyroid nodules from January
      2000 to December 2001. RESULTS: Three hundred and seventeen nodules from 267
      patients were aspirated. The average size of nodules was 0.9 +/- 0.3 cm, a range
      of 0.2 cm to 1.5 cm. All 317 lesions were impalpable. Cytological diagnosis
      included 101 inadequate specimen (32%), 139 benign (44%), 29 indeterminate (9%),
      four suspicious of follicular or Hurthle cell neoplasm (1%), 42 papillary
      carcinoma (13%) and two others. The size of the nodule was not related to the
      probability of getting an adequate specimen for cytological diagnosis. Forty of
      48 patients with suspicious or malignant cytology underwent surgery. All 35
      patients with a cytological diagnosis of papillary carcinoma were confirmed to
      have papillary carcinoma on histological results. One of three patients with a
      cytological diagnosis of follicular neoplasm had a follicular carcinoma. In 36
      patients with well-differentiated thyroid cancer, extrathyroidal extension was
      observed in 44% (16/36), regional lymph node metastasis was found in 50% (18/36)
      and multifocal tumours were found in 39% (14/36). CONCLUSIONS: The rate of
      malignancy in incidentally detected impalpable thyroid nodules was 12% in
      retrospective analysis of our patients. In this subgroup, 69% (25/36) of patients
      had either extrathyroidal extension or regional node involvement and 39% had
      multifocal tumours at surgery. This suggests that the small size alone does not
      guarantee low risk in incidentally found thyroid cancers. USGFNA is a useful
      diagnostic method in these patients.

PMID- 14678284
TI  - Cortisol levels and mortality in severe sepsis.
AB  - OBJECTIVE: Serum cortisol levels rise in response to the stress of critical
      illness but the optimal range of serum cortisol in such settings is not clearly
      defined. The objectives of this study were to determine the range of serum
      cortisol levels in a group of medical intensive care unit patients with severe
      sepsis/septic shock using uniform criteria, and to correlate serum cortisol
      levels to mortality. DESIGN AND PATIENTS: In a prospective observational fashion,
      100 medical intensive care unit patients at Northwestern Memorial Hospital in
      Chicago were enrolled within 48 h of developing severe sepsis/septic shock as
      defined by the American College of Chest Physicians/Society of Critical Care
      Medicine. MEASUREMENTS: A serum cortisol level was measured during the morning
      hours in the first 48 h of developing severe sepsis/septic shock. The severity of
      critical illness was measured by the Acute Physiology and Chronic Health
      Evaluation II (APACHE II) score. RESULTS: The average patient age was 63 +/- 17
      years, 54 patients were men. The average APACHE II score for all patients was 23
      +/- 7. In-hospital and 90-day mortality were 51% and 60%, respectively. Four
      patient groups were defined a priori based on morning serum cortisol levels and
      their in-hospital mortalities were as follows: group 1 (cortisol < or = 345
      nmol/l), n = 11, mortality 54%; group 2 (cortisol 345-552 nmol/l), n = 19,
      mortality 53%; group 3 (cortisol 552-1242 nmol/l), n = 54, mortality 41%; and
      group 4 (cortisol > or = 1242 nmol/l), n = 16, mortality 81% (P < 0.01).
      CONCLUSIONS: Cortisol levels were elevated in most patients with septic shock.
      Cortisol levels less than 552 nmol/l occurred in 30% of patients with septic
      shock but the mortality in these patients was not significantly increased. Serum
      cortisol levels > or = 1242 nmol/l were associated with significantly higher
      mortality.

PMID- 14678285
TI  - The first homozygous mutation (S226I) in the highly-conserved WSXWS-like motif of
      the GH receptor causing Laron syndrome: supression of GH secretion by GnRH
      analogue therapy not restored by dihydrotestosterone administration.
AB  - OBJECTIVE: The study describes for the first time, a homozygous mutation in the
      WSXWS-like motif of the human GH receptor (GHR) in a patient with Laron syndrome
      and describe laboratory data during treatment with GnRHa to suppress puberty and
      dihydrotestosterone (DHT). PATIENTS: A 16-year-old boy at Tanner puberty stage 2
      with Laron syndrome was born SGA to consanguineous parents, presented severe
      growth retardation, obesity and micropenis. METHODS AND MEASUREMENTS: GHR coding
      region was sequenced. GH, GHBP, IGF-I and IGFBP-3 were determined before, during
      and after GnRHa and DHT treatment. RESULTS: A homozygous mutation in exon 7,
      replacing serine by isoleucine in codon 226 was identified. S226 is the last
      serine belonging to the WSXWS-like motif in GHR. No specific effect of S226I
      mutation in heterozygous state was observed. Laboratory data at the prepubertal
      age showed markedly high GH, low GHBP, IGF-I and IGFBP-3 levels. Re-evaluation at
      pubertal age showed normal basal serum IGFBP-3 levels and low but near normal IGF
      I levels. We also noticed a sustained decrease in GH, IGF-I and IGFBP-3 levels
      after blocking puberty, which was not affected by short- and long-term DHT
      treatment. Pubertal hormonal profile was re-established after the GnRHa therapy
      was discontinued to allow the reactivation of the gonadal axis. CONCLUSION: The
      homozygous mutation S226I in WSXWS-like motif of GHR causes GH insensitivity. The
      decrease in IGF-I and IGFBP-3 levels after GnRHa therapy, which was not reversed
      with DHT administration, suggests that sex steroids have, through oestradiol, a
      GH-independent action on IGF-I and IGFBP-3 levels. A direct effect of GnRHa on GH
      secretion cannot be excluded.

PMID- 14678286
TI  - Obese patients with obstructive sleep apnoea syndrome show a peculiar alteration
      of the corticotroph but not of the thyrotroph and lactotroph function.
AB  - OBJECTIVE: Obstructive sleep apnoea syndrome (OSAS) is strongly associated with
      obesity (OB) and is characterized by several changes in endocrine functions, e.g.
      GH/IGF-I axis, adrenal and thyroid activity. It is still unclear whether these
      alterations simply reflect overweight or include peculiar hypoxia-induced
      hormonal alterations. Hormonal evaluations have been generally performed in basal
      conditions but we have recently reported that OSAS is characterized by a more
      severe reduction of the GH releasable pool in comparison to simple obesity. We
      aimed to extend our evaluation of anterior pituitary function to corticotroph,
      thyrotroph and lactotroph secretion under dynamic testing in OSAS in comparison
      with simply obese and normal subjects. SUBJECTS AND METHODS: In 15 male patients
      with OSAS [age, mean +/- SEM 43.5 +/- 1.6 years; body mass index (BMI) 39.2 +/-
      3.1 kg/m2; apnoea/hypopnoea index, (AHI) 53.4 +/- 8.7], 15 male patients with
      simple obesity (OB, age 39.7 +/- 1.2 years; BMI 41.2 +/- 2.0 kg/m2; AHI 3.1 +/-
      1.2 events/h of sleep) and in 15 normal lean male subjects (NS, age 38.2 +/- 1.4
      years; BMI 21.2 +/- 0.8 kg/m2; AHI 1.9 +/- 0.8 events/h of sleep) we evaluated:
      (a) the ACTH and cortisol responses to CRH [2 microg/kg intravenously (i.v.)] and
      basal 24 h UFC levels; (b) the TSH and PRL responses to TRH (5 microg/kg iv) as
      well as FT3 and FT4 levels. RESULTS: Twenty-four-hour UFC levels in OSAS and OB
      were similar and within the normal range. Basal ACTH and cortisol levels were
      similar in all groups. However, the ACTH response to CRH in OSAS (Deltapeak: 30.3
      +/- 3.8 pmol/l; DeltaAUC: 682.8 +/- 128.4 pmol*h/l) was markedly higher (P <
      0.001) than in OB (Deltapeak: 9.3 +/- 1.4 pmol/l; DeltaAUC 471.5 +/- 97.3
      pmol*h/l), which, in turn, was higher (P < 0.05) than in NS (Deltapeak: 3.3 +/-
      0.9 pmol/l; DeltaAUC 94.7 +/- 76.7 pmol*h/l). On the other hand, the cortisol
      response to CRH was not significantly different in the three groups. Basal FT3
      and FT4 levels as well as the TSH response to TRH were similar in all groups.
      Similarly, both basal PRL levels and the PRL response to TRH were similar in the
      three groups. CONCLUSIONS: With respect to patients with simple abdominal
      obesity, obese patients with OSAS show a more remarkable enhancement of the ACTH
      response to CRH but a preserved TSH and PRL responsiveness to TRH. These findings
      indicate the existence of a peculiarly exaggerated ACTH hyper-responsiveness to
      CRH that would reflect hypoxia- and/or sleep-induced alterations of the neural
      control of corticotroph function; this further alteration is coupled to the
      previously described, peculiar reduction of somatotroph function.

PMID- 14678287
TI  - Stimulation of thyroid-stimulating hormone (TSH) receptor antibody production
      following painless thyroiditis.
AB  - OBJECTIVE: Development or recurrence of Graves' disease (GD) following painless
      thyroiditis (PT) has been documented. Therefore, we measured titres of TSH
      receptor antibodies (TSHR Ab) using a novel sensitive TSHR Ab assay in patients
      with PT to determine whether PT enhances TSHR Ab production, possibly triggering
      the development or recurrence of GD. DESIGN AND MEASUREMENTS: Ninety-two patients
      who developed PT were studied. Group G consisted of 40 patients with a history of
      GD (19 patients in remission, 21 who had stopped taking antithyroid drugs during
      pregnancy). Group P consisted of 52 patients with no history of GD. Serum thyroid
      hormone levels, thyroid autoantibodies including TSHR Ab, and 123I uptake at 24 h
      (RAIU) were measured in these patients at the time of PT onset. TSHR Abs were
      measured by radioreceptor assay using porcine TSH receptors (pTBII) or human TSH
      receptors (hTBII). RESULTS: There were no significant differences in serum
      thyroid hormone levels or pTBII values between groups G and P. Nor was there any
      significant difference between p- and h-TBII values in group P. There was also no
      significant difference in pTBII levels before, compared to at the time of PT
      onset in group G patients. However, hTBII values at the PT onset were
      significantly higher in the group G than in the group P (7.7 +/- 9.8%vs. 1.4 +/-
      5.4%, P = 0.0014). The rate of hTBII positivity was also significantly higher in
      group G than in group P (12/40 vs. 3/52, P = 0.002). Furthermore, the RAIU in
      group G patients was significantly higher than that in group P patients (2.8 +/-
      2.4%vs. 1.3 +/- 0.9%, P = 0.0002). GD recurrence was observed in seven patients
      in group G, whose hTBII levels were significantly higher than those of other
      patients in this group (17.0 +/- 11.8%vs. 5.7 +/- 8.2%, P = 0.02). Of these seven
      with relapses, five had hTBII values exceeding 15%. CONCLUSIONS: TBII elevation
      at the onset of PT in patients with a history of GD was detected by a sensitive
      hTBII assay. Destruction of the thyroid by PT may trigger GD recurrence in
      patients with a history of GD.

PMID- 14678288
TI  - N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) in different thyroid
      function states.
AB  - OBJECTIVE: N-terminal B-type natriuretic peptide (NT-pro-BNP) is secreted from
      the cardiac ventricles in response to volume expansion and pressure overload, and
      serum levels are elevated in systolic heart failure. The aim of this study was to
      evaluate the influence of thyroid function on NT-pro-BNP. DESIGN: Patients with
      overt or subclinical thyroid disease were evaluated before and after treatment
      for their dysthyroid state. PATIENTS: Seventeen overt and 21 subclinical
      hypothyroid patients together with six subclinical and 13 overt hyperthyroid
      patients without cardiac disease were included. Subclinical states had, by
      definition, free T4 and free T3 estimates within reference ranges. MEASUREMENTS:
      Serum levels of NT-pro-BNP and thyroid hormones were measured, and in 31 patients
      resting cardiac output was measured by impedance cardiography in the untreated
      state. RESULTS: NT-pro-BNP levels were more than four times higher in
      hyperthyroid than hypothyroid patients, with mean values of 30 and 7 pmol/l,
      respectively (P < 0.001). Serum NT-pro-BNP levels correlated to the thyroid
      function (vs. free T4 estimate: r = 0.52, P < 0.0001, n = 57). Treatment resulted
      in significant increases in NT-pro-BNP in both hypothyroid groups, and decreases
      in both hyperthyroid groups. A multiple linear regression analysis demonstrated
      that free T4 and free T3 (P < 0.001) estimates were independently associated with
      a high serum NT-pro-BNP, whereas cardiac output and resting pulse rate were not.
      CONCLUSIONS: Serum NT-pro-BNP levels are affected by thyroid function. This seems
      due to a direct stimulatory effect of thyroid hormones.

PMID- 14678289
TI  - Association between ghrelin and cardiovascular indexes in healthy obese and lean
      men.
AB  - OBJECTIVE: Obesity is an increasingly common condition and is associated with
      excess morbidity and mortality, including clinical and subclinical cardiac
      dysfunction. The role of hormones involved in energy homeostasis, including
      ghrelin and leptin, in cardiovascular function remains incompletely understood.
      Therefore, we sought to evaluate the association between systemic ghrelin and
      leptin levels with indexes of cardiovascular structure and function. DESIGN AND
      MEASUREMENTS: We measured serum ghrelin and leptin levels in 25 clinically
      healthy obese men and 25 lean controls, using commercially available
      immunoassays. We also assessed right and left ventricular structure and function
      using cardiac magnetic resonance imaging. We then investigated the association
      between serum ghrelin and leptin levels with cardiac indexes, using univariate
      and multivariate analysis. RESULTS: There was an independent association between
      serum ghrelin levels and height-adjusted right ventricular mass (r = -0.324, P =
      0.026), right ventricular end-diastolic volume (r = -0.363, P = 0.017) and right
      ventricular end-systolic volume (r = -0.398, P = 0.009) as well as right
      ventricular ejection fraction (r = 0.317, P = 0.050). There was no significant
      association between serum ghrelin and indexes of left ventricular structure or
      function. We also identified an association between serum leptin levels and
      resting heart rate (r = 0.391, P = 0.002). There was an association between serum
      leptin and height-adjusted left ventricular mass on univariate, but not on
      multivariate, analysis. CONCLUSIONS: Serum ghrelin is associated with right
      ventricular cardiovascular indexes and serum leptin is associated with resting
      heart rate. These associations indicate a close interaction between the endocrine
      and cardiovascular systems in obesity.

PMID- 14678290
TI  - Relationship of GnRH-stimulated LH release to episodic LH secretion and baseline
      endocrine-metabolic measures in women with polycystic ovary syndrome.
AB  - BACKGROUND AND OBJECTIVE: In polycystic ovary syndrome (PCOS) inappropriate
      gonadotrophin secretion is characterized by increased pulse frequency and
      amplitude, elevated 24-h mean serum concentrations, and greater responses to
      GnRH. While the mechanism(s) responsible for this increased release of LH are not
      well understood, enhanced LH secretion has been attributed to increased pituitary
      sensitivity to GnRH and feedback influences from circulating steroid hormones. To
      address these considerations, we conducted a study to examine the relationships
      between GnRH-stimulated LH responses, episodic gonadotrophin secretion, and
      baseline measurements of endocrine-metabolic function in PCOS. PATIENTS: Serum LH
      responses to sequential multidose GnRH administration and pulsatile gonadotrophin
      secretion were examined in 13 PCOS and 13 normal women. MEASUREMENTS: Serum LH,
      steroid hormone, insulin and glucose levels were determined in blood samples
      obtained during assessment of episodic gonadotrophin secretion and LH responses
      to GnRH stimulation. DESIGN: Each subject was studied on two consecutive days. On
      study day 1 each subject underwent frequent blood sampling every 10 min for 12 h.
      On study day 2 each received sequential doses of GnRH, 2 microg, 10 microg and 20
      microg, administered intravenously at 4-h intervals over a continuous 12-h
      period. RESULTS: Serum LH responses following GnRH were markedly greater in PCOS
      compared to normal women, as expected. In individual PCOS, peak LH responses to
      GnRH were significantly correlated with corresponding basal LH and LH pulse
      amplitude, but not LH pulse frequency. In the PCOS group, LH responses were
      positively correlated with serum oestradiol (E2) and inversely related to body
      mass index (BMI). Between-group differences in LH responsiveness disappeared when
      controlling for serum testosterone (T) levels. CONCLUSIONS: These results
      indicate that the absolute LH increment following GnRH is largely dependent on
      baseline LH levels and may account for the well-documented difference in LH
      responsiveness between PCOS and normal women. That neither LH responses to GnRH
      nor LH pulse amplitude were correlated to LH pulse frequency suggests involvement
      of other factors along with GnRH to account for increased LH secretion in PCOS.
      In addition to E2 and BMI, serum testosterone appears to be, at least in part,
      responsible for differences in LH secretion and release between PCOS and normal
      women.

PMID- 14678291
TI  - Serum paraoxonase activity before and after treatment of thyrotoxicosis.
AB  - OBJECTIVE: Antioxidant effects of paraoxonase, a high density lipoprotein (HDL)
      associated enzyme that inhibits low density lipoprotein cholesterol (LDL-C)
      oxidation in human serum, have been reported. Patients with thyroid dysfunction
      are more susceptible to oxidative stress, and may show enhanced LDL-C oxidation.
      The purpose of this study was to evaluate serum paraoxonase activity in patients
      with hyperthyroidism before and after treatment with methimazole (MMI). DESIGN
      AND PATIENTS: Twenty-four hyperthyroid patients (15 women and nine men, aged 43.0
      +/- 12.9 years) and 23 age- and sex-matched healthy controls were studied. Serum
      paraoxonase activity, lipid, lipoprotein and apolipoprotein levels were measured
      in fasting samples. Patients were treated with MMI 20-30 mg daily for the first
      month, and 5-10 mg daily thereafter, and re-evaluated after 6-9 months of
      treatment. RESULTS: Significantly lower serum paraoxonase activity was present in
      hyperthyroid patients before treatment compared with the controls (43.4 +/- 21.9
      vs. 72.6 +/- 41.2 U/ml, P < 0.005). After a mean follow-up of 7.3 months, 15
      patients became euthyroid (treated) and nine were still hyperthyroid. After
      follow-up, serum paraoxonase activity had increased to 62.2 +/- 37.4 U/ml in
      those who became euthyroid (P < 0.05 compared with baseline). In patients who
      were still hyperthyroid serum paraoxonase was unchanged from baseline, at 43.2 +/
      23.2 U/ml. CONCLUSION: Serum paraoxonase is reduced in patients with
      hyperthyroidism and reverts to normal after euthyroidism is attained. Reduced
      serum paraoxonase activity in thyrotoxicosis might predispose lipids to
      oxidation.

PMID- 14678292
TI  - Vitamin D status in female patients with primary hyperparathyroidism: does it
      play a role in skeletal damage?
AB  - OBJECTIVE: Vitamin D deficiency, even subclinical, has been considered to worsen
      the skeletal damage in primary hyperparathyroidism (PHPT). Our study aimed to
      investigate the impact of vitamin D status on skeletal involvement in PHPT.
      DESIGN AND MEASUREMENTS: A cross-sectional study was designed involving 62 female
      patients with PHPT. Serum total calcium (tCa), phosphate (P), creatinine (Cr) and
      total alkaline phosphatase activity (AP), together with 24-h (uCa 24 h) and spot
      fasting (uCa/Cr) urinary calcium, were measured by autoanalyser; ionized calcium
      (iCa) was assessed by an ion-specific electrode; intact parathyroid hormone (PTH)
      was measured by immunoradiometric assay (IRMA) and 25-hydroxyvitamin D (25-OHD)
      by radioimmunoassay (RIA). Bone mineral density (BMD) was measured by dual energy
      X-ray absorptiometry (DXA) at lumbar spine in 58 patients, and at femoral neck,
      Ward's triangle, greater trochanter, intertrochanteric line and total hip in 56
      patients. The associations of all variables with age, 25-OHD, body mass index
      (BMI) and PTH were studied by linear multiple regression analysis, using
      progressively restricted models. RESULTS: The model including age, 25-OHD, PTH
      and BMI showed significant regression with BMD values. PTH, age and BMI exerted a
      leading role in determining such a significance, while no significant regression
      was found between the parameters studied and 25-OHD; this was confirmed by
      Pearson's linear correlation analysis. The progressively restricted models showed
      significant regression of BMD at femoral neck, femoral intertrochanteric line and
      total hip with age, BMI and PTH. BMD measured at the Ward's triangle and greater
      trochanter showed significant regression with age and BMI, and that measured at
      lumbar spine with age. CONCLUSIONS: Our data indicate that in primary
      hyperparathyroidism patients the influence of 25-hydroxyvitamin D levels on bone
      mineral density, if any, was overwhelmed by the effects of parathyroid hormone
      excess, age and body mass index. The latter unequally affected bone mineral
      density of various measured sites with different composition.

PMID- 14678293
TI  - Serum osteoprotegerin and receptor activator of nuclear factors kB (RANKL)
      concentrations in normal children and in children with pubertal precocity,
      Turner's syndrome and rheumatoid arthritis.
AB  - BACKGROUND: Osteoprotegerin (OPG) is a secreted member of the TNF receptor
      superfamily. OPG is made by osteoblastic cells and is expressed in a wide variety
      of cell and tissue types. It acts as a decoy receptor by binding the receptor
      activator of nuclear factors kB (RANKL) and preventing RANKL-induced osteoclast
      formation and differentiation. Numerous cytokines and hormones (TGF-beta, PTH,
      vitamin D, glucocorticoids and oestrogens) exert their effects on
      osteoclastogenesis by regulating the production of OPG. PATIENTS AND METHODS: In
      the present study we compared serum OPG and RANKL concentrations in a group of
      normal children (1-14 years old) with those of pair-aged children affected by
      different diseases [Turner's syndrome (TS), early/precocious puberty (PP) and
      rheumatoid arthritis (RA)]. OPG and RANKL concentrations were measured by an
      enzyme immunoassay method using a commercial kit. RESULTS: Mean (+/- SD) OPG
      level in normal children was 4.05 +/- 1.63 pmol/l with no difference between
      males and females. OPG values in children 1-4 years old (5.87 +/- 2.22 pmol/l)
      were significantly higher than in children 4-14 years old (3.55 +/- 0.97 pmol/l).
      OPG levels in children with RA were significantly higher than in controls (6.33
      +/- 2.57 pmol/l vs. 4.05 +/- 1.63 pmol/l, P < 0.01); patients with TS or PP had
      OPG levels superimposable to those of controls (2.61 +/- 0.67 pmol/l and 3.99 +/-
      0.85 pmol/l, respectively), but in TS OPG levels were significantly lower than in
      age-matched females. Mean RANKL concentration in normal subjects was 0.81 +/-
      1.55 pmol/l; there was a slight decline in RANKL levels with age. RANKL
      concentrations in subjects with TS, PP, RA and controls did not differ
      significantly, and did not differ from those published in adult normal subjects.
      CONCLUSIONS: It appears from our data that OPG serum levels in healthy children
      aged > 4 years are similar to those present in young adult men, with higher
      levels in the first 4 years of life. Although the meaning of the alterations of
      OPG levels observed in pathological conditions is still obscure, they appear
      potentially interesting in view of a key role played by this protein in bone
      homeostasis.

PMID- 14678294
TI  - Growth hormone replacement in adults and bone mineral density: a systematic
      review and meta-analysis.
AB  - BACKGROUND: The effect of GH replacement on bone mineral density (BMD) in adults
      with GH deficiency (GHD) is uncertain. We carried out a systematic review of
      randomized trials that compared GH to no active treatment, with BMD as an
      outcome. METHODS: We searched electronic databases to identify articles,
      abstracts and conference proceedings to March 2002. We also checked reference
      lists in included studies and expert reviews. Two reviewers independently
      extracted the data on study design and change in BMD. The results of individual
      trials were combined by fixed effects model meta-analysis using weighted mean
      difference (WMD) of change in BMD at the lumbar spine (our primary outcome) and
      other sites. FINDINGS: Eighteen trials that included 700 patients met the
      inclusion criteria. Maximum follow-up was for 12 weeks (1 trial), 6 months (14
      trials), 12 months (1 trial), 18 months (1 trial) and 24 months (1 trial).
      Reporting quality of both study design and results was poor. Ten trials (458
      subjects) were included in the meta-analysis. We excluded those eight trials from
      which sufficient data could not be extracted. We found a mean change in BMD, at
      the lumbar spine with GH treatment, of 0.01 g/cm2 after 6 and 12 months, 0.02
      g/cm2 after 18 months and 0.03 g/cm2 after 24 months. Statistical significance at
      the 0.05 level was just achieved at 6 and 12 months but was significant at 18 and
      24 months. These changes are small and may be influenced by bias. CONCLUSION:
      There is evidence of a small effect of GH replacement on bone mineral density in
      adults with GH deficiency. The clinical importance of this is uncertain.

PMID- 14678295
TI  - A reappraisal of the Rb1 gene abnormalities in the diagnosis of parathyroid
      cancer.
AB  - OBJECTIVES: Some histological features may suggest the malignant nature of a
      parathyroid tumour. However, the diagnosis of parathyroid cancer can only be
      definitively established in the presence of local invasion or metastases. DESIGN:
      We further investigated the role of the retinoblastoma gene (Rb1) and the breast
      cancer susceptibility gene (BRCA2) in the differential diagnosis between benign
      and malignant parathyroid tumours by evaluating loss of heterozygosity (LOH) at
      these loci and Rb protein (pRb) immunohistochemistry. PATIENTS AND MEASUREMENTS:
      Fifty-three parathyroid adenomas from patients with sporadic primary
      hyperparathyroidism (PHPT) and 10 parathyroid cancer specimens were studied.
      Microsatellite polymorphisms at the Rb1 and BRCA2 loci were polymerase chain
      reaction (PCR) amplified from each patient's paired tumour and leucocyte DNA
      samples, using oligonucleotide primers flanking the repeat sequence.
      Immunohistochemical staining of pRb was carried out using a monoclonal antibody.
      RESULTS: All but one of the 53 tumour-leucocyte pairs was informative for at
      least one of the three polymorphic markers of the Rb1 gene. Fifteen adenomas
      (28.8%) showed LOH. Regarding the BRCA2 gene, 46 tumour-leucocyte pairs were
      informative and LOH was present in eight (17.4%). All six carcinomas had LOH for
      at least one marker at the Rb1 locus. LOH for the BRCA2 microsatellite was found
      in three of the five informative primary tumour samples. Immunohistochemical
      analysis revealed that all adenomas were positive and the number of pRb-positive
      cells varied significantly among different samples. The mean percentage of
      stained cells was 15.7%. Eleven of the 30 (36.7%) adenomas showed sparse positive
      staining, 13 (43.3%) intermediate staining and six (20%) extensive staining. All
      parathyroid cancers were entirely negative for pRb immunostaining. CONCLUSIONS:
      Inactivation of the Rb1 gene is a common event in parathyroid tumorigenesis.
      Retention of heterozygosity seems to exclude parathyroid malignancy, which is
      suggested by the combined finding of LOH and lack of protein expression.

PMID- 14678297
TI  - FSH and LH responses to GnRH after ovariectomy in postmenopausal women.
AB  - OBJECTIVE: Whether the postmenopausal ovary is still playing a role in the
      control of gonadotrophin secretion in response to GnRH has not been investigated.
      The aim of the present study was to test this hypothesis by examining changes in
      basal and GnRH-induced gonadotrophin secretion in postmenopausal women after
      bilateral ovariectomy. DESIGN: The responses of LH and FSH to GnRH [10 microg
      intravenously (i.v.)] were investigated in postmenopausal women from 2 days
      before to 8 days after total abdominal hysterectomy plus bilateral ovariectomy.
      PATIENTS: Nine postmenopausal women aged 52-67 years and between 5 and 15 years
      after menopause. In all cases the ovaries were histologically normal.
      MEASUREMENTS: Pituitary responses to GnRH were calculated every 12-24 h as the
      net increases in LH (DeltaLH) and FSH (DeltaFSH) at 30 min above the basal
      values. Basal values of oestradiol (E2) and testosterone were also measured.
      RESULTS: Basal values of FSH showed a significant decrease on postoperative days
      2 (P < 0.01) and 8 (P = 0.03) as compared to day 0, while at the same time points
      after the operation LH values were marginally lower than on day 2 (P = 0.05).
      Serum E2 values showed a gradual increase up to postoperative day 1 (P = 0.04)
      and a gradual decline thereafter. Basal testosterone concentrations decreased
      gradually and significantly after ovariectomy and were significantly lower on day
      8 than on day 0 (P < 0.01). DeltaFSH and DeltaLH responses to GnRH did not change
      significantly with time. A temporary increase at 12 h after the operation was not
      significant. CONCLUSIONS: These results demonstrate for the first time that the
      removal of the ovaries in postmenopausal women does not affect GnRH-induced
      gonadotrophin secretion in the short term. It is suggested that the
      postmenopausal ovary is not a dominant regulator of hypothalamic-pituitary
      interactions.

PMID- 14678296
TI  - Expression, subcellular localization and phosphorylation status of annexins 1 and
      5 in human pituitary adenomas and a growth hormone-secreting carcinoma.
AB  - OBJECTIVE: Annexin 1 (ANXA1), a 37-kDa protein, plays an important role as a
      mediator of glucocorticoid action in the anterior pituitary gland and has been
      implicated in the processes of tumorigenesis in a number of other tissues. As a
      prelude to examining the potential role of ANXA1 in the pathophysiology of
      pituitary tumours, this study examined the expression, phosphorylation status and
      distribution of ANXA1 and the closely related protein, annexin 5 (ANXA5), in a
      series of pituitary adenomas and in two carcinomas. PATIENTS AND DESIGN: Forty
      two human pituitary adenomas were examined. Parallel studies were performed on
      normal pituitary tissue, obtained postmortem, a GH-secreting carcinoma and a
      grade 4 astrocytoma. MEASUREMENTS: The tissue was processed for analysis of ANXA1
      mRNA and protein expression by reverse transcriptase polymerase chain reaction
      (RT-PCR), Western blot analysis and immunogold electron-microscopic
      histochemistry. Parallel measures of ANXA5 mRNA and protein were also made.
      RESULTS: ANXA1 mRNA and protein were detected in all but three adenomas studied;
      the protein was localized mainly, but not exclusively, to nonendocrine cells.
      ANXA5 expression was more variable and was contained within both endocrine and
      nonendocrine cells of these tumours. In comparison with the adenomas, the GH
      secreting carcinoma showed abundant expression of both ANXA1 and ANXA5, with
      intense ANXA1 staining in some but not all tumour/endocrine cells. A serine
      phosphorylated species of ANXA1 was detected in all pituitary tumours studied; by
      contrast, tyrosine-phosphorylated ANXA1 was detected in only four adenomas and in
      the GH carcinoma. ANXA1 and ANXA5 were also expressed in abundance in the
      astrocytoma. CONCLUSIONS: The results demonstrate expression of both ANXA1 and
      ANXA5 in human pituitary tumours and thus raise the possibility that these
      proteins influence the growth and/or functional activity of the tumours.

PMID- 14678298
TI  - Impaired trafficking of mutated AVP prohormone in cells expressing rare disease
      genes causing autosomal dominant familial neurohypophyseal diabetes insipidus.
AB  - OBJECTIVE AND STUDY DESIGN: Two different mutations in the arginine vasopressin
      (AVP) gene associated with autosomal dominant familial neurohypophyseal diabetes
      insipidus (adFNDI) predict Y21H (AVP2) and V67A (NP36) amino acid substitutions
      of the AVP prohormone. They are unique in that they change, respectively, the AVP
      moiety and a region of the neurophysin II domain not so far affected by any
      mutations. To test whether they affect the cellular handling of the AVP
      prohormone in a similar manner to previously investigated mutations, they were
      examined by heterologous expression in cell lines. RESULTS: Both mutations
      resulted in significantly reduced amounts of immunoreactive AVP in the cell
      culture medium as determined by radioimmunoassay analysis. Metabolic labelling
      combined with immunoprecipitation demonstrated that processing and secretion of
      the mutant prohormones was reduced but not prevented. Finally, confocal laser
      scanning microscopy showed that normal AVP prohormone and/or its processed
      products were localized in the tips of the cellular processes, whereas both
      mutant prohormones were accumulated in the endoplasmic reticulum (ER) and in the
      case of the V67A prohormone, also in perinuclear structures outside the ER.
      CONCLUSION: Both mutations result in reduced AVP prohormone processing and
      secretion probably due to retention in the ER. This supports, at least partly,
      the hypothesis that the mutations lead to the production of a mutant hormone
      precursor that fails to fold and/or dimerize properly and, as a consequence, is
      retained by the ER protein quality control machinery. Perinuclear accumulation of
      the V67A prohormone outside the ER indicates that additional mechanisms could be
      involved.

PMID- 14678300
TI  - Cushing's disease as the first clinical manifestation of multiple endocrine
      neoplasia type 1 (MEN1) associated with an R460X mutation of the MEN1 gene.

PMID- 14678299
TI  - The relationship of ghrelin to biochemical and anthropometric markers of adult
      growth hormone deficiency.
AB  - INTRODUCTION: Ghrelin is the natural ligand of the growth hormone secretagogue
      receptor (GHS-R) and potently stimulates GH release in humans. Ghrelin is found
      in the hypothalamus, but most circulating ghrelin is derived from the stomach.
      Ghrelin stimulates food intake but circulating levels are low in obesity. We
      hypothesized that GH deficiency (GHD) might be associated with increased
      circulating ghrelin concentrations as a result of low GH levels. We therefore
      measured circulating ghrelin concentrations, leptin and body composition in
      subjects with GHD and healthy controls. METHODS: Subjects with GHD (n = 18) were
      compared to healthy control subjects (n = 18), matched for body mass index (BMI).
      They underwent assessment of body composition [waist circumference, BMI and
      percentage body fat (using bioimpedance)]. Plasma ghrelin, leptin, insulin, GH
      and IGF-1 were measured in the fasting state. Plasma ghrelin was measured using a
      specific radioimmunassay, and the other hormones using commercially available
      assays. RESULTS: The groups were well-matched for BMI (GHD vs. control; 32.9 +/-
      10.8 vs. 31.3 +/- 11.7, P = ns) and waist circumference (GHD vs. control; 102.9
      +/- 20.0 vs. 99.8 +/- 25.2, P = ns), but percentage body fat (GHD vs. control;
      37.0 +/- 9.1 vs. 29.4 +/- 13.0, P = 0.06) tended to be higher in the GHD group.
      As expected, IGF-1 was lower in GHD (GHD vs. control; 12.5 +/- 6.8 vs. 19.2 +/-
      5.8 nmol/l, P = 0.003). Ghrelin [GHD vs. controls; geometric mean (95% CI); 828.8
      (95% CI 639.9-1074.2) vs. 487.9 (95% CI 297.2-800.2) pmol/l] and leptin [GHD vs.
      controls; 13.2 (95% CI 6.6-26.5) vs. 7.9 (95% CI 3.7-16.9) ng/ml] were similar in
      the two groups. Plasma ghrelin correlated inversely with waist circumference and
      waist hip ratio in GHD subjects (r = -0.6, P = 0.02) but not with IGF-1 or GH
      concentrations. There was no significant correlation in the control subjects.
      CONCLUSION: Circulating ghrelin concentrations are influenced by body fat
      distribution, but not by levels of either GH or IGF-1. However, given that
      obesity is associated with reduced ghrelin concentrations and that GHD is
      commonly associated with increased body fat, it is possible that these two
      opposing influences on circulating ghrelin levels result in normal concentrations
      in subjects with GHD.

PMID- 14678301
TI  - Reversal of polycythaemia induced by intramuscular androgen replacement using
      transdermal testosterone therapy.

PMID- 14678302
TI  - Tall stories: the fundamental difficulties of genetic association studies.

PMID- 14678303
TI  - Increased expression of endothelin-1 converting enzyme in human thyroid
      carcinoma.

PMID- 14678304
TI  - Analysis of the PROP1 gene in a large cohort of patients with idiopathic
      hypogonadotropic hypogonadism.

PMID- 14678305
TI  - Neonatal Group B streptococcal infection at the Mount Hope Women's Hospital,
      Trinidad.
AB  - OBJECTIVE: To determine the incidence of early onset Group B streptococcal (GBS)
      infection in neonates at the Mount Hope Women's Hospital, Trinidad over the
      period 1996-97. DESIGN AND METHODS: This retrospective study included all babies
      with a positive blood culture for GBS during the study period. RESULTS: There
      were 9866 live births (LB) of whom 29 were diagnosed as early onset GBS disease.
      The incidence was 2.9/1000 LB. 37.9% of babies were preterm and 65.5% were
      delivered to primiparous women. Rupture of amniotic membranes occurred within 12
      h of delivery in 55% of infected babies. Four of the 29 infected babies died and
      all were preterm. CONCLUSION: The incidence of early onset neonatal GBS sepsis
      was five to six times higher in this series than that reported in the USA and UK.
      An intervention policy to control this preventable disease is urgently needed.

PMID- 14678306
TI  - Developmental, behavioural and somatic factors in pervasive developmental
      disorders: preliminary analysis.
AB  - OBJECTIVES: To ascertain the frequency of parental reporting of selected
      variables related to development, behaviour and physiology in subgroups diagnosed
      with pervasive developmental disorders (PDDs) and identify any significant
      intragroup differences. DESIGN: Retrospective cross-sectional analysis of records
      of patients (n = 512) held on a computerized database with a chronological age
      between 3 and 11 years resident in the UK/Republic of Ireland and with a formal
      diagnosis of autism, Asperger syndrome (AS) or autism spectrum disorder (ASD).
      METHODS: Non-parametric analysis (P > 0.01) of the frequency of specific
      variables for PDD subgroups reported by parents/primary caregiver. VARIABLES
      INCLUDED: timing of symptom onset, presence of skills acquired prior to symptom
      onset, indications of regression and regression events, current language, history
      of viral infections, history of ear problems, achievement of continence, current
      skin complaints, current bowel habits and adverse events at parturition. RESULTS:
      Preliminary results showed general agreement with the principle diagnostic
      differences between the PDD subgroups with patients diagnosed with AS showing an
      increased frequency of skills acquired before symptom onset (two- to three-word
      phrase speech, toileting skills) and a decreased frequency of regression in
      acquired skills when compared with other PDD subgroups. Developmental milestones
      such as the achievement of bowel and bladder continence were also more frequently
      reported for the AS group. Infantile feeding problems defined as vomiting,
      reflux, colic and failure to feed were more frequently reported for the AS group
      as was a reported history of the bacterial skin infection impetigo. Results are
      discussed with reference to relationships between behavioural and somatic factors
      in PDD.

PMID- 14678307
TI  - Care co-ordination and key worker schemes for disabled children: results of a UK
      wide survey.
AB  - AIM: To investigate the prevalence and nature of care co-ordination and key
      worker services for disabled children and their families. METHODS: Postal survey
      of 225 Children with Disabilities Teams across the UK. RESULTS: Out of 159
      questionnaires returned (70%), 35 (22%) reported having a care co-ordination
      scheme, with 30 (19%) of these providing key workers for families. The majority
      had multiagency and parent involvement in setting up and overseeing the schemes.
      However, multiagency funding was less common and funding for many schemes was
      short term. Different models of key working were apparent. Five schemes employed
      full-time key workers. In 21 schemes, professionals key worked with a few
      families as part of a larger case load, and in three schemes, both types of key
      workers were employed. Most schemes provided initial or ongoing training for key
      workers, but a few provided neither of these. DISCUSSION: The proportion of areas
      having care co-ordination or key worker services is consistent with findings on
      research with parents of disabled children, which reports that less than one
      third of families have a key worker. The extent of multiagency involvement in
      planning and overseeing the operation of the service was positive but joint
      funding was more problematic. There was considerable variation in service models
      and as yet, little is known about whether or how such variations relate to
      outcomes for children and families. Further research will investigate these
      issues.

PMID- 14678308
TI  - Mothers' mental health and infant growth: a case-control study from Rawalpindi,
      Pakistan.
AB  - BACKGROUND: Epidemiological studies in Pakistan show high rates of depression in
      women, while rates of malnutrition in children are also high. This study aimed to
      determine whether poor maternal mental health is associated with an increased
      risk of infant undernutrition. METHODS: Clinic-based case-control study. A total
      of 172 consecutive infants and their mothers attending for 9-month measles
      immunization were recruited over a 3-month period. Eighty-two undernourished
      infants [weight for age below the National Centre for Health Statistics
      (NCHS)/World Health Organization (WHO) third centile] were matched to 90 controls
      (weight for age above 10th centile), and their mothers interviewed for mental
      distress using the Self-Reporting Questionnaire (WHO SRQ-20, a psychiatric
      screening instrument). Infants' exposure to maternal distress (score > or = 10 on
      SRQ-20) and other potential risk or protective biological, social, socio-economic
      and family factors were measured. RESULTS: Mental distress determined by WHO SRQ
      20 was associated with increased risk of undernutrition in infants (odds ratio
      3.91, 95% confidence interval 1.95-7.86). This association remained significant
      after controlling for birthweight and social factors. CONCLUSION: Exposure to
      maternal mental distress is associated with undernutrition in 9-month infants in
      urban Pakistan. These mothers may represent a group whose children are at higher
      risk of ill health, and potentially be a specific target for advice on infant
      care. Early recognition and treatment of mental health problems in mothers may
      help reduce morbidity and mortality rates in children.

PMID- 14678309
TI  - Absence from childcare for respiratory illness.
AB  - BACKGROUND: This population-based study investigated prospectively collected
      absence for respiratory illness data in two types of formal childcare (centre day
      care and family day care) in Perth, Western Australia, and factors associated
      with such absence. METHODS: All centres (n = 11) and 95% of family day care
      caregivers (n = 130) selected at random from licensing lists agreed to
      participate. Demographic details were obtained from a parental questionnaire and
      absences were recorded prospectively. Characteristics of the child and family
      were described using univariate odds ratios (OR) with 95% confidence intervals
      (CI). Multivariable analysis including generalized estimating equations was used
      to investigate having at least one absence for respiratory illness, having two or
      more absences, and having six or more absences. RESULTS: No statistically
      significant difference between care types for having had at least one absence
      episode for respiratory illness (OR 1.37, 95% CI 0.92-2.04) was found. Children
      who attended care for more days per week (OR 1.40, 95% CI 1.26-1.56) and those in
      the study for more weeks (OR 1.03, 95% CI 1.01-1.05) were more likely to be
      absent for respiratory illness. Those children in care for a greater number of
      hours per day were less likely to be absent (OR 0.88, 95% CI 0.80-0.97). Family
      history of bronchitis was also associated with absence for respiratory illness
      (OR 1.86, 95% CI 1.32-2.63). CONCLUSIONS: Statistically significant factors which
      had an impact on absence for respiratory illness were primarily those relating to
      the time spent in childcare and to family history of bronchitis.

PMID- 14678310
TI  - Children's beliefs about the importance of gender in transgression situations.
AB  - OBJECTIVE: In previous research, several variables are shown to have an impact on
      children's perception of gender. The aim of this study was to examine the
      relation between discipline methods and the child's beliefs about the importance
      of gender in transgression situations. METHODS: In this study, variables such as
      type of siblings, socioeconomic status, child's sex, parental values and shared
      responsibility are controlled for. Two hundred and five 8-year-old children in
      Sweden were interviewed about discipline methods in five transgression situations
      and their parents were asked to fill in a battery of questions. RESULTS: The
      results show that harsher discipline methods, such as behaviour modification,
      physical restraint and physical punishment, relate to stronger beliefs about the
      importance of gender in transgression situations.

PMID- 14678311
TI  - The health of Swedish-speaking and Finnish-speaking schoolchildren in Finland.
AB  - BACKGROUND: It is well known that Swedish-speaking adults in Finland have higher
      life expectancy and better health than their Finnish-speaking counterparts. Among
      young people, similar comparisons have been scarce. The present paper aims to
      compare the health of Swedish-speaking and Finnish-speaking schoolchildren.
      METHODS: Survey data from 1997, representing children at grades 8 and 9 of
      compulsory school in a bilingual region, are analysed with the help of logistic
      regression models. Self-rated health as well as objective measures of health are
      explored. RESULTS: We find that Swedish-speaking schoolchildren are healthier
      than Finnish-speaking ones in terms of objective measures of health, whereas
      there is no difference between language groups in terms of self-assessed health.
      Self-rated health seems to reflect well-being in a very broad context rather than
      objective health from a medical perspective. Risk factors and health behaviours
      being equal, both language groups consequently assess their health in a similar
      manner. CONCLUSIONS: Policy makers should be careful when advocating the health
      needs of schoolchildren based on survey results concerned with self-assessed
      health measures, particularly when they are concerned with targeting measures
      towards specific subgroups of the population. Self-rated health is obviously not
      well suited for reflecting overall and specific needs of medical assistance and
      expertise for schoolchildren.

PMID- 14678312
TI  - Parental review of service uptake during the pre-school period.
AB  - This article outlines the development and analysis of the results of a community
      led survey undertaken in year 1 of a 3-year period of evaluation for a first wave
      Sure Start programme. The survey had initially been suggested as a means of
      collecting data that was required, at the time, by the central Sure Start unit,
      however, its potential outside of this specific evaluative purpose was also
      recognized. In addition to providing important pointers for the future
      development of the programme, the findings give insight into a community within
      the west midland conurbation, and reviews the support that carers have accessed
      during the first 4 years of their youngest child's life. Their feelings and
      opinions are presented and demonstrate factors that influence the involvement of
      carers in this and other related programmes.

PMID- 14678313
TI  - Infant hospitalization and maternal depression, poverty and single parenthood - a
      population-based study.
AB  - OBJECTIVES: There is variation in rates of hospitalization for young children
      which is unexplained by differences in health. We used population-based survey
      data to examine the contribution of family sociodemographic and psychodynamic
      factors to the risk of hospitalization in children under the age of 2 years in
      Canada. METHODS: Baseline data from the National Longitudinal Survey of Children
      and Youth (a population-based study of child health and well-being) were used. A
      weighted sample of 332 697 (unweighted n = 2184) children between the age of 12
      and 24 months, whose biological mother reported data on hospitalization over the
      past year, were included. Logistic regression analyses were conducted to estimate
      the risk of hospitalization by sociodemographic and psychodynamic factors
      controlling for important biological covariates. RESULTS: The overall proportion
      of children who were hospitalized was 11.2%. After adjusting for prematurity, the
      only statistically significant biological factor associated with the risk of
      hospitalization was reported present health [odds ratio (OR) 4.04, 95% confidence
      intervals (CI): 2.93, 5.58]. However, three family variables were significantly
      associated with hospitalization: low income adequacy (OR 1.66, 95% CI: 1.15,
      2.40), single parenthood (OR 1.55, 95% CI: 1.03, 2.34) and maternal depression
      (OR 1.81, 95% CI: 1.22, 2.69). Having a parent who is a recent immigrant to
      Canada is associated with a reduced risk of hospitalization (OR 0.53, 95% CI:
      0.35, 0.78). CONCLUSIONS: Most of the significant associations with
      hospitalization in the first 2 years of life in the Canadian population relate to
      the overall family's social and mental health. Maternal depression is a treatable
      disorder which if recognized might prevent some infant morbidity.

PMID- 14678314
TI  - Frequency and determinants of formal respite service use among caregivers of
      children with cerebral palsy in Ontario.
AB  - OBJECTIVE: To describe the use of formal respite services among caregivers of
      children with cerebral palsy in Ontario and discuss the factors that may
      contribute to respite use and non-use. METHODS: A total of 468 caregivers were
      interviewed about their experience with formal respite services. Interviews were
      part of a larger cross-sectional study on caregiver health. Caregivers were asked
      about their knowledge of formal respite services; their use of formal respite
      services in the past year; financial implications relating to formal respite use;
      perceived barriers to formal respite service use; and reasons for not using
      formal respite services (if applicable). RESULTS: Nearly half (46%) of caregivers
      in the sample reported using respite services in the past year. Most of the
      caregivers who used respite services used more than one source of respite, had
      services provided in their home, often for less than 1 day, and reported using
      them more than six times. The most commonly cited reason for using formal respite
      services was for a planned break. Many factors influenced caregivers' use of
      formal respite services. Caregivers who had a child with a lower level of
      function, with multiple additional conditions, or who was male, were more likely
      to use formal respite services. Although over 90% of caregivers indicated that
      respite use is beneficial for both their family and child, over 60% reported
      facing many barriers while attempting to access respite services. CONCLUSION:
      Results from this cross-sectional study indicate that caregivers who used respite
      services used them frequently for breaks from caregiving. Caregivers described
      facing many barriers while attempting to access respite services therefore to
      improve caregiver's experience with respite services, strategies are suggested.

PMID- 14678326
TI  - Immunity to Salmonella from a dendritic point of view.
AB  - Dendritic cells (DC) are the key link between innate and adaptive immunity.
      Features of DC, including their presence at sites of antigen entry, their ability
      to migrate from peripheral sites to secondary lymphoid organs, and their superior
      capacity to stimulate naive T cells places them in this pivotal role in the
      immune system. DC also produce cytokines, particularly IL-12, upon antigen
      encounter and can thus influence the ensuing adaptive immune response. As DC are
      phagocytic antigen-presenting cells located at sites exposed to bacterial
      invaders, studies have been performed to gain insight into the role of DC in
      combating bacterial infections. Indeed, studies with Salmonella have shown that
      DC can internalize and process this bacterium for peptide presentation on MHC-II
      as well as MHC-I. DC can also act as bystander antigen--presenting cells by
      presenting Salmonella antigens after internalizing neighbouring cells that have
      undergone Salmonella-induced apoptotic death. DC also produce IL-12 and TNF-alpha
      upon Salmonella encounter. Moreover, studies in a murine infection model have
      shown that splenic DC increase surface expression of co-stimulatory molecules
      during infection, and DC contain intracellular bacteria. In addition,
      quantitative changes occur in splenic DC numbers in the early stages of oral
      Salmonella infection, and this is accompanied by redistribution of the defined DC
      subsets in the spleen of infected mice. DC from Salmonella-infected mice also
      produce cytokines and can stimulate bacteria-specific T cells upon ex vivo co
      culture. In addition, DC may play a role in the traversal of bacteria from the
      intestinal lumen. Studying the function of DC during Salmonella infection
      provides insight into the capacity of this sophisticated antigen-presenting cell
      to initiate and modulate the immune response to bacteria.

PMID- 14678327
TI  - Immune biasing by helminth glycans.
AB  - The ability of helminth parasites to drive polarized Th2 responses has been known
      for some time. Interestingly, many recent studies have shown that helminth
      expressed glycan activation of host immune cells accounts for much of the anti
      inflammatory and Th2-biasing observed. This microreview attempts to cover the
      biology of expression of immunomodulatory glycans in various helminth parasites,
      the immune cells they interact with including the production of cytokines,
      chemokines and antibodies. We also discuss the potential cell surface receptors
      which are capable of binding certain glycans and the known mech-anisms which
      ultimately lead to production of anti-inflammatory mediators as well as
      polarizing CD4+ T-cell responses to Th2-type in the host. Lastly, we discuss a
      novel mechanism for activation of antigen-presenting cells by a specific helminth
      glycan that leads to maturation of Type 2 dendritic cells.

PMID- 14678328
TI  - From toxin to adjuvant: the rational design of a vaccine adjuvant vector, CTA1
      DD/ISCOM.
AB  - Mucosally active vaccine adjuvants which will prime a full range of local and
      systemic immune responses against defined antigenic epitopes are much needed.
      Cholera toxin (CT) and lipophilic immune stimulating complexes (ISCOMs)
      containing Quil A can both act as adjuvants for orally administered antigens, but
      through separate pathways, as evidenced by the dependence on IL-12 for the effect
      of ISCOMs, whereas CT is independent of this cytokine. Unfortunately the toxicity
      of CT and recent findings of accumulation of CT in the olfactory nerve and bulb
      after intranasal administration precludes the clinical use of CT. However, we
      have been successful in separating the adjuvant and toxic effects of CT, by
      constructing a gene fusion protein, CTA1-DD, that combines the enzymatically
      active CTA1-subunit with a B cell targeting moiety, D, derived from
      Staphylococcus aureus protein A. The present review gives a background to mucosal
      immunization and the use of -adjuvants in general, followed by a description of a
      strategy to rationally design a vaccine adjuvant vector that fulfils the criteria
      of targeting and immunomodulating innate immunity in order to boost a strong
      adaptive immune response. We have combined CTA1-DD and ISCOMs into a new highly
      promising vaccine adjuvant vector, CTA1-DD/ISCOMs. The combined vector is
      immunogenic when given by the subcutaneous, oral or nasal routes, inducing strong
      cell--mediated and humoral immune responses, including local mucosal IgA. It
      requires the ADP ribosylating property of the CTA1-enzyme and the effect of the
      combined vector greatly exceeded the effect of either ISCOMs or CT used alone.
      Antigens could be incorporated into or just admixed with the new vector. Thus, we
      have demonstrated that rationally designed vectors consisting of CTA1-DD and
      ISCOMS may provide a novel strategy for the generation of potent and safe mucosal
      vaccines.

PMID- 14678329
TI  - Activation of caspase-3 by the Dot/Icm virulence system is essential for arrested
      biogenesis of the Legionella-containing phagosome.
AB  - The Dot/Icm type IV secretion system of Legionella pneumophila is essential for
      evasion of endocytic fusion and for activation of caspase-3 during early stages
      of infection of macrophages, but the mechanisms of manipulating these host cell
      processes are not known. Here, we show that caspase-3 activation by L.
      pneumophila is independent of all the known apoptotic pathways that converge on
      the activation of caspase-3. The cytoplasmic proteins IcmS, IcmR and IcmQ, which
      are involved in secretion of Dot/Icm effectors, are required for caspase-3
      activation. Pretreatment of U937 macrophages and human peripheral blood monocytes
      (hPBM) with the capase-3 inhibitor (DEVD-fmk) or the paninhibitor of caspases (Z
      VAD-fmk) before infection blocks intracellular replication of L. pneumophila in a
      dose-dependent manner. Inhibition of caspase-3 results in co-localization of the
      L. pneumophila-containing phagosome (LCP) with the late endosomal/lysosomal
      marker Lamp-2, and the LCP contains lysosomal enzymes, similar to the dotA
      mutant, which is defective in caspase-3 activation. However, activation of
      caspase-3 before infection does not rescue the replication defect of the dotA
      mutant. Interestingly, inhibition of caspase-3 after a 15 or 30 min infection
      period by the parental strain has no detectable effect on the formation of a
      replicative niche. The Dot/Icm-mediated activation of caspase-3 by L. pneumophila
      specifically cleaves, in a dose- and time-dependent manner, the Rab5 effector
      Rabaptin-5, which maintains Rab5-GTP on the endosomal membrane. In addition, PI3
      kinase, which is a crucial effector of Rab5 downstream of Rababptin-5, is not
      required for intracellular replication. Using single-cell analysis, we show that
      apoptosis is not evident in the infected cell until bacterial replication results
      in > 20 bacteria per cell. We conclude that activation of caspase-3 by the
      Dot/Icm virulence system of L. pneumophila is essential for halting biogenesis of
      the LCP through the endosomal/lysosomal pathway, and that this is associated with
      the cleavage of Rabpatin-5.

PMID- 14678330
TI  - Cystic fibrosis airway epithelial cell polarity and bacterial flagellin determine
      host response to Pseudomonas aeruginosa.
AB  - The role of epithelial polarity and bacterial factors in the control of the
      innate immune response of airway epithelial cells to Pseudomonas aeruginosa PAK
      was investigated using a human, nasal cystic fibrosis (DeltaF508/DeltaF508)
      epithelial cell line CF15 grown as confluent layers on permeable supports.
      Addition of PAK to the basal surface of CF15 layers caused significant expression
      changes in 1525 different genes (out of 12 625 examined), including the cytokines
      IL-6, IL-8, IL-1beta and TNF-alpha, as well as genes associated with leucocyte
      adhesion, antibacterial factors, and NF-kappaB signalling. Confocal microscopy
      showed that nuclear migration of NF-kappaB in all CF15 cells was preceded by PAK
      binding to the basal and lateral surfaces of some cells. Addition of PAK to the
      apical surface of CF15 monolayers elicited changes in expression of only 602
      genes, including 256 not affected during basolateral PAK exposure. Over time,
      cytokine expression during apical PAK was similar to that exhibited by basal PAK,
      but the magnitudes during apical treatment were much smaller with little/no
      nuclear migration of NF-kappaB in CF15 cells. Furthermore, these responses
      depended on the presence of flagellin, but not pili on the bacteria. Thus, P.
      aeruginosa triggered a strong innate immune response that depended on the apical
      versus basolateral polarity of CF15 cells and the presence of flagellin on the
      bacteria.

PMID- 14678331
TI  - Gene targeting demonstrates that the Plasmodium berghei subtilisin PbSUB2 is
      essential for red cell invasion and reveals spontaneous genetic recombination
      events.
AB  - The Plasmodium merozoite proteases involved in the crucial process of erythrocyte
      invasion are promising targets for novel malaria control strategies. We report
      here the characterization of the subtilisin-like protease SUB2 from the rodent
      parasites Plasmodium berghei and Plasmodium yoelii, leading the way to in vivo
      functional studies of this enzyme. The kinetics of expression and subcellular
      localization imply a central role for SUB2 in erythrocyte invasion. Through the
      use of gene targeting strategies, we assessed the relevance of P. berghei SUB2
      for the intraerythrocytic cycle. The selection of recombinant Pbsub2
      TrimycDuoXpress-tagged parasites and the proper expression of the modified coding
      region demonstrate that the Pbsub2 locus is accessible to genetic modifications.
      However, Pbsub2 knock-out parasites were not recovered, confirming the importance
      of PbSUB2 for P. berghei merozoite stages, and supporting the fact that its
      Plasmodium falciparum SUB2 orthologue is an attractive drug target candidate.
      Finally, we identify revertant parasites that have lost the integrated selection
      cassette while conserving a Pbsub2-tagged gene. These spontaneous reversion
      events should overcome the scarcity of selectable markers available for this
      parasite, giving access to multiple gene tagging strategies, which, together with
      the validation of a TrimycDuoXpress tag, would represent valuable new tools for
      studying the biology of P. berghei.

PMID- 14678332
TI  - Enolase from Streptococcus sobrinus is an immunosuppressive protein.
AB  - A strategy of Streptococcus sobrinus, a major agent of dental caries, to survive
      and colonize the host consists of the production of a protein that suppresses the
      specific antibody responses. We have cloned the gene coding for a protein with
      immunosuppressive activity. It contains an open reading frame of 1302 base pairs
      encoding a polypeptide with 434 amino acid residues and a molecular mass of 46910
      Da. The gene product is homologous to enolases from several organisms. The
      polypeptide was expressed in Escherichia coli as a hexahistidine-tagged protein
      and purified in a fluoride-sensitive enzymatically active form. Pretreatment of
      mice with the S. sobrinus recombinant enolase suppresses a primary immune
      response against T-cell dependent antigens. This immunosuppressive effect is
      specific to the antigen used in the immunization, as it is not observed when the
      immune response against other antigens is analysed. Furthermore, the S. sobrinus
      recombinant enolase stimulates an early production of interleukin-10, an anti
      inflammatory cytokine, and not the pro-inflammatory cytokine IFN-gamma. These
      observations indicate that enolase acts in the suppression of the specific host
      immune response against S. sobrinus infection.

PMID- 14678333
TI  - Effect of the insect pathogenic bacterium Photorhabdus on insect phagocytes.
AB  - Photorhabdus are insect pathogenic bacteria that replicate within the insect
      haemocoel following release from their entomopathogenic nematode symbionts. To
      investigate how they escape the cellular immune response we examined the effects
      of two strains of Photorhabdus, W14 and K122, on Manduca sexta phagocytes
      (haemocytes), in vitro and in vivo. Following injection of Esherichia coli into
      Manduca larvae, these non-pathogenic bacteria are rapidly cleared from the
      haemolymph and the number of free haemocytes transiently increases. In contrast,
      following injection of either strain of pathogenic Photorhabdus, the bacteria
      grow rapidly while the number of haemocytes decreases dramatically. In vitro
      incubation of haemocytes with either Photorhabdus supernatant reduced haemocyte
      viability, and the W14 supernatant caused distinct changes in the actin
      cytoskeleton morphology of different haemocyte cell types. In phagocytosis assays
      both Photorhabdus strains can inhibit their own phagocytosis whether the
      bacterial cells are alive or dead. Further, the supernatant of W14 also contains
      a factor capable of inhibiting the phagocytosis of labelled E. coli. Together
      these results suggest that Photorhabdus evades the cellular immune response by
      killing haemocytes and suppressing phagocytosis by mechanisms that differ between
      strains.

PMID- 14678335
TI  - Age-related changes in pharmacokinetics and pharmacodynamics: basic principles
      and practical applications.
AB  - Advancing age is characterized by impairment in the function of the many
      regulatory processes that provide functional integration between cells and
      organs. Therefore, there may be a failure to maintain homeostasis under
      conditions of physiological stress. The reduced homeostatic ability affects
      different regulatory systems in different subjects, thus explaining at least
      partly the increased interindividual variability occurring as people get older.
      Important pharmacokinetic and pharmacodynamic changes occur with advancing age.
      Pharmacokinetic changes include a reduction in renal and hepatic clearance and an
      increase in volume of distribution of lipid soluble drugs (hence prolongation of
      elimination half-life) whereas pharmacodynamic changes involve altered (usually
      increased) sensitivity to several classes of drugs such as anticoagulants,
      cardiovascular and psychotropic drugs. This review focuses on the main age
      related physiological changes affecting different organ systems and their
      implications for pharmacokinetics and pharmacodynamics of drugs.

PMID- 14678336
TI  - Stroke, dementia, and drug delivery.
AB  - Stroke and dementia represent a major health burden for elderly subjects as they
      are associated with significant morbidity and mortality. The rates of stroke and
      dementia are progressively increasing due to the ageing population in most
      westernized countries. Therefore, both these conditions represent a major
      therapeutic target. However, the therapeutic options available for the management
      of stroke and dementia remain largely unsatisfactory, the main reason being the
      difficulty in transferring the results obtained in animal and in vitro studies to
      the clinical setting. This review focuses on the recent advances in
      pathophysiology and treatment of these conditions and future directions for
      research. Moreover, the technique of functional magnetic resonance imaging is
      discussed in detail as a tool to assess the effects of therapeutic agents on the
      central nervous system and monitor the progression of diseases. Finally, an
      overview of the issue of drug delivery into the central nervous system is
      presented.

PMID- 14678337
TI  - Vasopeptidase inhibitors: will they have a role in clinical practice?
AB  - The human cardiovascular system is regulated by haemodynamic, neurohumoral and
      structural mechanisms. The endothelium and the neurohumoral system play a key
      role in modulating both vascular tone and structure by producing vasoactive
      substances, and in the modulation of blood cell adhesion. Although the
      neurohormonal systems are essential in vascular homeostasis, they become
      maladaptive in conditions such as hypertension, coronary disease and heart
      failure. The clinical success of blocking the renin-angiotensin system by
      angiotensin converting enzyme (ACE)-inhibitors and the sympathetic nerve system
      by beta-blockers demonstrates the importance of neurohumoral blockade. The
      inadequate effect of angiotensin converting enzyme (ACE) or neutral endopeptidase
      (NEP) inhibitor monotherapy seen in some patients treated for hypertension or
      congestive heart failure, and the promising effect seen after their combination,
      led to the development of drugs that simultaneously inhibit both enzyme systems.
      Neutral endopeptidase, like ACE, is an endothelial cell surface zinc
      metallopeptidase with similar structure and catalytic site to ACE. NEP is the
      major enzymatic pathway for degradation of natriuretic peptides. The natriuretic
      peptide system can be viewed as the endogenous inhibitor of the renin angiotensin
      system. The dual metalloprotease inhibitors of ACE and NEP, called vasopeptidase
      inhibitors therefore represent a new and attractive therapeutic strategy for the
      treatment of cardiovascular disease. The ability to add incremental benefit over
      already proven therapy, with an acceptable side-effect profile however, is
      questionable in this new class of agents.

PMID- 14678338
TI  - Effects of passive smoking on blood pressure and aortic pressure waveform in
      healthy young adults--influence of gender.
AB  - AIMS: Passive smoking impairs the elasticity of the aorta in patients with
      coronary heart disease. We therefore studied the effect of passive smoking on
      wave reflection in the aorta, a marker of arterial stiffness, in healthy
      subjects. METHOD: We examined the effects of acute exposure to passive smoking on
      blood pressure and the aortic pressure waveform in healthy young men (n = 10) and
      women (n = 11), aged 26 +/- 5 years (mean +/- SEM) compared with 12 healthy
      controls, aged 24 +/- 2 years (six female) who were exposed to room air. The
      aortic pressure waveform was derived with radial applanation tonometry
      (SphygmoCor, AtCor Medical, version 6.2) and the augmentation index, a measure of
      arterial wave reflection in the aorta, calculated. Blood pressure (Omron Model
      HEM-705 CP, Omron Corporation, Tokyo, Japan) and augmentation index were measured
      at baseline, 15, 30 and 60 min after exposure to environmental tobacco smoke
      (carbon monoxide 25-30 p.p.m. for 60 min) or room air. RESULTS: Passive smoking
      was associated with an increase in brachial (124 +/- 4-137 +/- 3 mmHg, P < 0.01)
      and aortic systolic blood pressure (110 +/- 3-123 +/- 4 mmHg, P < 0.01) at 60 min
      in the male subjects only. The augmentation index increased from -1.7 +/- 5 to 14
      +/- 5 at 60 min (P < 0.001) only in the male subjects. The transit time of the
      pulse did not change significantly. The change in augmentation index was
      independent of the increase in blood pressure. Brachial and aortic diastolic
      blood pressure and heart rate did not change significantly in either male or
      female subjects. No haemodynamic changes were observed in the control group.
      CONCLUSIONS: Acute exposure to passive smoking has a deleterious effect on the
      arterial pressure waveform in healthy young males but not in females, suggesting
      a possible protection of female gender from functional changes in arteries.

PMID- 14678340
TI  - Effect of age on the pharmacokinetics of duloxetine in women.
AB  - AIMS: The effect of age on duloxetine pharmacokinetics was evaluated in healthy
      volunteers and in patients with urinary incontinence. METHODS: Twenty-four
      healthy subjects (12 women 65-77 years, and 12 women 32-50 years) were given a
      single 40-mg oral dose of duloxetine in Study 1. Plasma concentration-time data
      were analysed by noncompartmental pharmacokinetic methods. Sparse plasma samples
      were obtained from patients with urinary incontinence treated in two phase II
      studies: 70 women (24-77 years) who received duloxetine 20 mg day(-1), 30 mg day(
      1), or 40 mg day(-1) in Study 2A and 128 women (28-64 years) who received
      duloxetine 20 mg day(-1), 40 mg day(-1), or 80 mg day(-1) in Study 2B. Based upon
      the combined data, a model was developed to characterize population
      pharmacokinetics of duloxetine using the nonlinear mixed-effects modelling
      program (NONMEM). RESULTS: In Study 1, the elderly (> or = 65 years) exhibited a
      statistically significant slower elimination rate constant lambdaz compared with
      younger subjects [elderly-younger difference = -0.022 h(-1)[95% confidence
      interval (CI) -0.036, -0.008]]. However, no statistically significant differences
      in either CL/F [elderly-younger difference = -17.4 l h(-1) (95% CI -41.1, 6.23)]
      or V/F [elderly-younger difference = 115.9 l (95% CI -168.6, 400.4)] were
      observed. The population pharmacokinetic analysis of Studies 2A and 2B revealed
      that the CL/F of duloxetine decreased with increasing age. Despite statistical
      significance, the age effect only accounted for 3% of the interindividual
      variability in CL/F and unexplained sources of the variation in clearance were
      still substantial (> 50%). Adverse events were generally mild to moderate, and
      the incidence of adverse events was generally similar in elderly and non-elderly
      participants in these studies. CONCLUSIONS: Whereas the results suggest that age
      has an effect on duloxetine pharmacokinetics, primarily reflected as a slower
      lambdaz in the elderly, the magnitude of mean changes in CL/F, or V/F was small
      relative to the large interindividual variation in pharmacokinetics. Elderly
      participants had a safety profile of duloxetine comparable to their younger
      counterparts. Specific dose recommendations for duloxetine in the elderly are not
      warranted.

PMID- 14678339
TI  - Population pharmacokinetics of weekly docetaxel in patients with advanced cancer.
AB  - AIMS: Previous pharmacokinetic studies of the 3-weekly regimen (100 mg m(-2)
      every 3 weeks) of docetaxel have shown that docetaxel clearance is affected by
      liver function, body surface area, age, serum alpha1-acid glycoprotein and
      cytochrome P450 3A4 (CYP3A4) activity. However, the pharmacokinetics of a weekly
      docetaxel (40 mg m(-2) week(-1)) schedule are not well characterized. The aims of
      this study were (a) to investigate the pharmacokinetics of docetaxel (40 mg m(-2)
      week(-1)) using sparse concentration-time data collected from patients with
      advanced cancer and (b) to utilize a population pharmacokinetic approach to
      identify patient covariates that significantly influence the clearance of
      docetaxel when administered according to this regimen. METHODS: A two-compartment
      pharmacokinetic model was used to describe the docetaxel concentration-time data
      from 54 patients with advanced cancer. The mean population and individual
      posterior Bayesian estimates of docetaxel clearance were estimated using P-PHARM.
      The relationships between docetaxel clearance and 21 covariates were
      investigated. This included estimates of CYP3A4 function in each patient using
      the erythromycin breath test (1/tmax). Significant covariates were included into
      the final population pharmacokinetic model. Pharmacokinetic models were validated
      using a data splitting approach with a dataset consisting of 16 patients.
      RESULTS: Significant relationships were found between docetaxel clearance and
      1/tmax (erythromycin breath test parameter) and several of the liver function
      enzymes and CL was best described by the equation; CL = 21.51 + 217 (1/tmax) -
      0.13 (ALT). This final population pharmacokinetic model provided both precise and
      unbiased predictions of docetaxel concentrations in a validation group of
      patients and an estimate of the population mean (95% confidence interval)
      clearance of docetaxel was 30.13 l h(-1) (12.54, 46.04 l h(-1)) with an
      intersubject variability 30%. CONCLUSIONS: A population pharmacokinetic model has
      been developed and validated for weekly docetaxel (40 mg m(-2)) in patients with
      advanced cancer. These results indicate that CYP3A4 activity and hepatic function
      have an impact on the pharmacokinetics of docetaxel when administered weekly.

PMID- 14678341
TI  - Elimination of ephedrines in urine following multiple dosing: the consequences
      for athletes, in relation to doping control.
AB  - AIMS: To study the elimination of ephedrines with reference to the International
      Olympic Committee (IOC) doping control cut-off levels, following multiple dosing
      of over-the-counter decongestant preparations. METHODS: A double-blind study was
      performed in which 16 healthy male volunteers were administered either
      pseudoephedrine or phenylpropanolamine in maximal recommended therapeutic doses
      over a 36-h period. Urine was collected every two hours between 08:00 and 24:00 h
      and at 04:00 h throughout the testing period of three days. Urine drug levels
      were quantified using high performance liquid chromatography. Side-effects were
      assessed, including heart rate and blood pressure, every four hours between 08:00
      and 20:00 h. RESULTS: Mean (95% CI) total phenylpropanolamine and pseudoephedrine
      eliminated unchanged was 75 (88, 61) and 81 (92, 71)%, respectively. Maximum
      urine concentrations of phenylpropanolamine and pseudoephedrine were 112.1
      (164.2, 59.9) and 148.5 (215.0, 82.1) mg.l(-1), respectively. A peak in drug
      urine concentration occurred four hours following the final dose. There were no
      adverse cardiovascular effects and only mild CNS stimulation was evident.
      CONCLUSIONS: Following therapeutic, multiple dosing, drug levels remain above the
      IOC cut-off levels for a minimum of 6 h and 16 h following final doses of
      phenylpropanolamine and pseudoephedrine, respectively. Athletes require informed
      advice on this from their healthcare professionals.

PMID- 14678342
TI  - The arginine-16 beta2-adrenoceptor polymorphism predisposes to bronchoprotective
      subsensitivity in patients treated with formoterol and salmeterol.
AB  - AIMS: The relationship between beta2-adrenoceptor polymorphisms and
      bronchoprotective response with long-acting beta2-adrenoceptor agonists is
      unknown. METHODS: We retrospectively analysed data from six placebo-controlled
      randomized studies in corticosteroid treated asthmatics where formoterol or
      salmeterol were administered over a 1-2-week period, with prior 1-2 week washout,
      assessing the primary end point of methacholine PD20 and adenosine monophosphate
      PC20, following first and last dose, expressed as doubling dose difference from
      placebo. RESULTS: There was no significant heterogeneity between the different
      studies. Patients who had homozygous or heterozygous genotypes containing the
      arginine-16 polymorphism (Arg16-Arg16 or Arg16-Gly16) had greater
      bronchoprotective subsensitivity compared with the homozygous glycine-16 genotype
      (Gly16-Gly16), amounting to a mean doubling dose difference of 1.49 (95% CI 0.50,
      2.48), after the last dose. Subsensitivity of response was greater with
      formoterol than salmeterol after the last dose in all genotypes, especially with
      the arginine-16 polymorphism, amounting to a doubling dose difference of 3.00
      (95% CI 1.01, 4.99) between formoterol and salmeterol. CONCLUSIONS: Our
      retrospective analysis showed that the arginine-16 polymorphism was associated
      with subsensitivity of response for bronchoprotection, which was greater for
      formoterol than salmeterol. A prospective study will be required in order to
      further evaluate these findings, particularly to assess whether these differences
      are mirrored by exacerbations.

PMID- 14678343
TI  - Clinical pharmacology studies in UK Phase 1 units: an AHPPI survey 1999-2000.
AB  - AIMS: This study, conducted by the Association for Human Pharmacology in the
      Pharmaceutical Industry (AHPPI), was designed to determine the amount of Phase 1
      activity in the UK in the period 1999-2000, the timelines involved for
      submissions to ethics committee and responses from ethics committees. METHODS: A
      questionnaire was completed by AHIPPI members from pharmaceutical companies with
      in-house phase 1 units, by Clinical Research Organizations (CRO's) and by
      academic centres. A few responses were also vailable from organisations that were
      not AHPPI members. Results were rendered anonymous and grouped by category.
      RESULTS: The response rate was > 98% and indicated that the vast majority of
      early drug research in humans is now CRO-based (82%). The total number of studies
      (as indicated by protocol numbers) was notably similar across the 2 years--629 in
      1999 and 606 in 2000. Turnaround time for ethics committee review was a mean of
      14 days. CONCLUSIONS: These data set important benchmarks for early-phase drug
      research in the UK where regulatory approval is not currently required.
      Furthermore, the information should be used as a guide if the competitive nature
      of such work in the UK is to be maintained as new national legislation is
      implemented following publication of the European Union (EU) Clinical Trials
      Directive.

PMID- 14678344
TI  - Quality of drug information on the World Wide Web and strategies to improve pages
      with poor information quality. An intervention study on pages about sildenafil.
AB  - AIMS: The generally poor quality of health information on the world wide web
      (WWW) has caused preventable adverse outcomes. Quality management of information
      on the internet is therefore critical given its widespread use. In order to
      develop strategies for the safe use of drugs, we scored general and content
      quality of pages about sildenafil and performed an intervention to improve their
      quality. METHODS: The internet was searched with Yahoo and AltaVista for pages
      about sildenafil and 303 pages were included. For assessment of content quality a
      score based on accuracy and completeness of essential drug information was
      assigned. For assessment of general quality, four criteria were evaluated and
      their association with high content quality was determined by multivariate
      logistic regression analysis. The pages were randomly allocated to either control
      or intervention group. Evaluation took place before, as well as 7 and 22 weeks
      after an intervention which consisted of two letters with individualized feedback
      information on the respective page which were sent electronically to the address
      mentioned on the page. RESULTS: Providing references to scientific publications
      or prescribing information was significantly associated with high content quality
      (odds ratio: 8.2, 95% CI 3.2, 20.5). The intervention had no influence on general
      or content quality. CONCLUSIONS: To prevent adverse outcomes caused by
      misinformation on the WWW individualized feedback to the address mentioned on the
      page was ineffective. It is currently probably the most straight-forward approach
      to inform lay persons about indicators of high information quality, i.e. the
      provision of references.

PMID- 14678345
TI  - Differences between clinical trials and postmarketing use.
AB  - AIMS: Clinical trials constitute the gold standard to assess the efficacy and
      safety of new medicines. However, because they are conducted in standardized
      conditions far from the real world of prescription and use, discrepancies in
      patient selection or treatment conditions may alter both the effectiveness and
      risks. On the basis of three examples, our objectives were to study the
      differences between the characteristics of treated populations and treatment
      patterns in clinical trials and in postmarketing settings and to discuss the
      potential consequences on actual efficacy and safety. METHODS: Treated
      populations were compared with patients included in premarketing clinical trials.
      Comparisons were made on the basis of demographic characteristics and treatment
      patterns. RESULTS: Whatever the indicator and the drug studied, differences were
      observed: from 0.04% to 63% for tacrine, from 0% to 37% for celecoxib and from 6%
      to 52% for simvastatin, with possible consequences on the effectiveness and
      safety of the drug concerned. Our results confirm the under-representation of
      women and elderly patients in premarketing clinical trials, e.g. an M : F ratio
      of 4.6 in clinical trails of simvastatin vs 1.0 in the joint population.
      Moreover, the concomitant use of medicines was made extremely restrictive by the
      protocols of these trials while this was not the case in the postmarketing phase.
      This has possible consequences on the effectiveness and safety of the drug
      concerned. CONCLUSIONS: These results plead for systematic ad hoc observational
      postmarketing studies for any novel and/or expensive medicine to assess the
      relevance of premarketing data.

PMID- 14678346
TI  - Safety evaluation of fixed combination piperaquine plus dihydroartemisinin
      (Artekin) in Cambodian children and adults with malaria.
AB  - AIMS: To assess the haemodynamic, electrocardiographic and glycaemic effects of
      piperaquine-dihydroartemisinin (Artekin) fixed combination therapy in
      uncomplicated malaria. METHODS: Sixty-two Cambodians (32 children and 30 adults)
      with falciparum or vivax malaria were given Artekin given as four age-based oral
      doses over 32 h. Supine and erect blood pressure, the electrocardiographic QT
      interval and plasma glucose were measured before treatment and then at regular
      intervals during a 4-day admission period as part of efficacy and safety
      monitoring. QT intervals were rate-corrected (QTc) using Bazett's formula.
      RESULTS: Artekin therapy was well tolerated and all patients responded to
      treatment. Average parasite and fever clearance times were 19 and 12 h,
      respectively. The pretreatment mean fall in systolic blood pressure on standing
      was 8 +/- 6 mmHg and 6-hourly measurements over 72 h showed no significant change
      (P = 0.48). There was a significant lengthening of the mean QTc to a maximum of
      11 ms(0.5) (95% confidence interval 4-18 ms(0.5)) relative to baseline at 24 h (P
      = 0.003). The maximal QTc prolongation observed in any patient was 53 ms(0.5).
      There was a mean 0.4 mmol l(-1) reduction in the post-absorptive plasma glucose
      during the first 48 h but no episodes of hypoglycaemia (plasma glucose < 3.0 mmol
      l(-1)) were observed at any time. CONCLUSIONS: Artekin is safe and effective
      combination therapy for uncomplicated malaria in children and adults. Although
      piperaquine is a long half-life drug related to other quinoline compounds
      including chloroquine and quinine, no clinically significant cardiovascular or
      metabolic effects were observed.

PMID- 14678347
TI  - Acute systemic effects of inhaled salbutamol in asthmatic subjects expressing
      common homozygous beta2-adrenoceptor haplotypes at positions 16 and 27.
AB  - AIMS: The relationship between beta2-adrenoceptor polymorphisms at positions 16
      and 27, and the acute systemic beta2-adrenoceptor effects of inhaled salbutamol
      is unclear. We therefore elected to evaluate the influence of common homozygous
      beta2-adrenoceptor haplotypes on the acute systemic beta2-adrenoceptor effects
      following inhaled salbutamol in asthmatic subjects. METHODS: An initial database
      search of 531 asthmatic subjects identified the two commonest homozygous
      haplotypes at positions 16 and 27 to be Arg16-Gln27 (12%) and Gly16-Glu27 (19%).
      After a 1-week washout period where all beta2-adrenoceptor agonists were
      withdrawn, 16 Caucasian subjects (Arg16-Gln27: n = 8 and Gly16-Glu27: n = 8) were
      given a single dose of inhaled salbutamol (1200 microg), followed by serial blood
      sampling for serum potassium, along with measurements of diastolic blood pressure
      and heart rate, at 5-min intervals for 20 min. RESULTS: The two groups were well
      matched for age, sex, FEV1, and inhaled corticosteroid dose. Baseline values for
      serum potassium, diastolic blood pressure and heart rate were not significantly
      different comparing Arg16-Gln27 vs Gly16-Glu27. The mean +/- SEM maximum serum
      potassium change from baseline over 20 min was significantly greater (P = 0.04)
      for Arg16-Gln27: -0.37 +/- 0.05 mmol l(-1) vs Gly16-Glu27: -0.23 +/- 0.04 mmol l(
      1); 95% CI for difference: -0.01 to -0.28 mmol l(-1). The maximum diastolic blood
      pressure change from baseline over 20 min was significantly greater (P = 0.0008)
      for Arg16-Gln27: -13 +/- 1 mmHg vs Gly16-Glu27: -4 +/- 2 mmHg; 95% CI for
      difference: -5, 14 mmHg. There was no significant difference comparing the
      maximum heart rate change from baseline for Arg16-Gln27: 10 +/- 3 beats min(-1)
      vs Gly16-Glu27: 10 +/- 3 beats min(-1). CONCLUSIONS: Caucasian asthmatic subjects
      with the Arg16-Gln27 haplotype exhibited a greater systemic response to inhaled
      salbutamol, compared with those with the Gly16-Glu27 haplotype. The attenuated
      beta2-adrenoceptor response in the Gly16-Glu27 haplotype would be in keeping with
      increased susceptibility to prior down-regulation by endogenous catecholamines.

PMID- 14678348
TI  - Large interindividual variability in the in vitro formation of tamoxifen
      metabolites related to the development of genotoxicity.
AB  - AIMS: To characterize the interindividual variability and the individual CYP
      involved in the formation of alpha-hydroxy-, N-desmethyl- and N-didesmethyl
      tamoxifen from tamoxifen. METHODS: Microsomes from 50 human livers were used to
      characterize the interindividual variability in the alpha-hydroxylation, N
      desmethylation and N-didesmethylation of tamoxifen. Selective inhibitors and
      recombinant enzymes were used to identify the forms of CYP catalysing these
      reactions. RESULTS: The rates of formation of alpha-hydroxy-, N-desmethyl- and N
      didesmethyl-tamoxifen were highly variable, and correlated with each other (P <
      0.0001). The respective ranges were 0.7-11.4, 25.7-411, and below the limit of
      quantification--4.4 pmol mg(-1) protein min(-1). Formation of all metabolites was
      observed with expressed recombinant CYP3A4, inhibited by troleandomycin (65, 77
      and 35%, respectively, P < 0.05) and associated with CYP3A4 expression (rs =
      0.612, rs = 0.585 and rs = 0.430, P < 0.01, respectively). CONCLUSIONS: Formation
      of alpha-hydroxy-, N-desmethyl- and N-didesmethyl-tamoxifen in vitro is highly
      variable and mediated predominantly by CYP3A4.

PMID- 14678352
TI  - Paediatric methylphenidate (Ritalin) restrictive conditions of prescription in
      France.

PMID- 14678354
TI  - Erectile dysfunction after radical prostatectomy.

PMID- 14678355
TI  - How do we investigate haematuria and what role has finasteride?

PMID- 14678356
TI  - Brachytherapy: the surgeon's perspective.

PMID- 14678357
TI  - Brachytherapy or radical prostatectomy: is there a preferred method for treating
      localized prostate cancer?

PMID- 14678358
TI  - The SPIRIT of research: a new well-funded randomized study comparing
      brachytherapy with radical prostatectomy is about to open in the UK.

PMID- 14678359
TI  - Cavernosal nerve mapping: current data and applications.
AB  - Although nerve-sparing prostatectomy is widely practised, the results with
      respect to preserving potency often do not meet expectations. The concept of
      intraoperative cavernosal nerve stimulation is reasonable. Data that link the
      response to sildenafil after prostatectomy with bilateral nerve sparing has
      increased the importance of optimizing nerve sparing. The cavernosal nerves are
      often difficult to visualize and may have a variable course. A tumescent response
      to nerve stimulation can be shown consistently; the response may be subtle, and
      characterized by a minimal increase in penile circumference and blood flow.
      Immediately after prostatectomy, proximal nerve stimulation identifies whether
      neural continuity has been maintained, and is predictive of recovery of erectile
      function. The Cavermap system (Uromed Corporation, Boston, MA, USA) was developed
      to permit intraoperative nerve stimulation with tumescence monitoring. An initial
      phase 2 and subsequent phase 3 single-blinded, randomized, multicentre study that
      compared Cavermap-assisted prostatectomy with conventional nerve sparing showed a
      significant benefit in terms of the duration of nocturnal tumescence at 1 year.
      Other approaches are being explored, including incorporating the device into
      sural or genito-femoral nerve grafting, use of nerve stimulation during
      cystectomy or abdominal-perineal resection, and direct corpus cavernosal pressure
      monitoring during nerve stimulation. These approaches warrant further evaluation.

PMID- 14678360
TI  - Third-generation cryosurgery for primary and recurrent prostate cancer.

PMID- 14678361
TI  - Genetic instability and transitional cell carcinoma of the bladder.
AB  - The development of cancer occurs in a stepwise fashion, with each step
      representing the mutation in one of several key genes. However, the mutation rate
      of somatic cells is too low to account for the number of mutations required for a
      cell to undergo carcinogenesis. Thus, the development of genetic instability is a
      vital early step towards carcinogenesis. We review the evidence for genetic
      instability, with particular reference to transitional cell carcinoma of the
      bladder. Both microsatellite instability and chromosomal instability are present
      in this tumour, and we discuss their incidence and clinical implications.

PMID- 14678362
TI  - The effect of continence surgery on urogenital prolapse.

PMID- 14678363
TI  - Devastating complications after brachytherapy in the treatment of prostate
      adenocarcinoma.
AB  - OBJECTIVE: To report a retrospective chart review of patients who developed recto
      urethral fistula (RUF) or several bladder neck contracture (BNC) recurrences
      after brachytherapy for treating localized prostate cancer. PATIENTS AND METHODS:
      In the past 3 years 18 patients with devastating complications after prostate
      brachytherapy were referred to our centre (RUF in 11, BNC in seven; mean age 63
      years, range 60-81). All patients with RUF initially underwent diverting
      colostomy (six cystoprostatectomy with closure of the fistula, omental
      interposition and urinary diversion; one prostatectomy, bladder neck closure,
      fistula closure with omentum flap and continent vesicostomy). Three patients had
      the fistula closed with gracilis muscle flap using the York-Mason approach (one
      had a bladder neck closure and suprapubic tube; one elected to have no
      treatment). All patients with BNC had received three or more procedures to resect
      or incise their contracture. Four had diversion with a catheterizable segment,
      two used an indwelling Foley catheter and one uses intermittent catheterization.
      RESULTS: All six patients who had cystoprostatectomy with urinary diversion have
      had no recurrence of their RUF. All three treated with the York-Mason procedure
      healed well. One developed recurrent prostate adenocarcinoma and two a secondary
      neoplasia in the prostate or rectum (leiomyosarcoma and neuroendocrine,
      respectively). The enterocystoplasty patient developed sepsis after colostomy
      reversal and subsequently died. In those patients with BNC, the four who
      underwent urinary diversion fared well; two tolerate the indwelling catheter
      poorly, and the seventh uses intermittent catheterization with occasional
      difficulty. CONCLUSIONS: Brachytherapy with or without external irradiation can
      be associated with severe complications. RUF managed with aggressive anterior
      pelvic exenteration and urinary diversion can be associated with excellent
      results. The York-Mason procedure in patients with an adequate urinary continence
      mechanism and bladder dynamics may provide good functional results. The presence
      of a secondary malignancy in patients deserves further investigation. Many
      recurrences of a BNC tend be refractory to transurethral resection/incision;
      indwelling catheters are then poorly tolerated and patients may require a major
      reconstructive procedure.

PMID- 14678364
TI  - Radiotherapy and hyperthermia in the treatment of patients with locally advanced
      prostate cancer: preliminary results.
AB  - OBJECTIVE: To report an interim clinical evaluation of combined external beam
      irradiation (EBRT) and interstitial or regional hyperthermia in the treatment of
      locally advanced prostate cancer. PATIENTS AND METHODS: From 1997 to 2001, 26
      patients with T3-4/NX/0M0 prostate carcinoma were treated with a combination of
      conformal EBRT and hyperthermia. Fourteen patients received five weekly regional
      hyperthermia treatments within an optimization (phase II) study, using the
      coaxial transverse electrical magnetic system. Twelve patients received one
      interstitial hyperthermia treatment within a feasibility study (phase I), using
      the multi-electrode current source system. Irradiation was delivered using a
      conformal three-field technique, administering 70 Gy in 2-Gy fractions in 7
      weeks. RESULTS: The mean initial prostate-specific antigen level was 26 ng/mL.
      Three patients had a T4 and 23 a T3 tumour; the tumours were classified as well
      (four), moderately (16) and poorly (six) differentiated. The mean follow-up was
      36 months. In the combined treatments there was no toxicity of more than grade 2.
      In regional hyperthermia the mean index temperature (T90 and T50, i.e. exceeded
      by 90% and 50% of the measurements) was 40.2 degrees C and 40.8 degrees C, and
      for interstitial hyperthermia 39.4 degrees C and 41.8 degrees C, respectively.
      All patients survived; seven patients had a biochemical relapse (27%), three in
      the regional and four in the interstitial group. The actuarial probability of
      freedom from biochemical relapse was 70% at 36 months for all patients together,
      79% for regional and 57% for interstitial. No factors were found that could be
      used to predict relapse. CONCLUSIONS: The clinical outcome in these patients with
      advanced localized prostate cancer seems to compare favourably with most series
      using irradiation alone, and the treatment caused no severe complications.

PMID- 14678365
TI  - Adjuvant goserelin improves clinical disease-free survival and reduces disease
      related mortality in patients with locally advanced or localized prostate cancer.
AB  - This article reviews the clinical disease-free survival (DFS) and disease-related
      mortality (DRM) data from published prospective, randomized trials of goserelin,
      given alone as adjuvant treatment or combined with a nonsteroidal antiandrogen as
      neoadjuvant treatment in patients with locally advanced or localized prostate
      cancer. Four trials were of radiotherapy and one of radical prostatectomy. The
      five trials included > 3500 patients and the median follow-up was 4.8-7.1 years.
      There were statistically significant improvements in clinical DFS with goserelin
      support relative to the control treatment in all five trials (each log-rank P </=
      0.004). Reductions in the risk of DRM were statistically significant with
      adjuvant goserelin vs no adjuvant treatment to support radiotherapy in one trial,
      and with adjuvant goserelin or bilateral orchidectomy vs no adjuvant treatment to
      support radical prostatectomy in another (each log-rank P </= 0.001). Time-point
      estimates of the rates of clinical DFS and DRM were in favour of goserelin
      support vs control in all five trials at 5 years and in the three trials for
      which data were available at 8 years. Goserelin support therefore improves
      clinical DFS and reduces DRM after radiotherapy or radical prostatectomy.
      Adjuvant goserelin may offer greater clinical benefits than neoadjuvant hormonal
      treatment.

PMID- 14678366
TI  - Patients' preferences for communicating a prostate cancer diagnosis and
      participating in medical decision-making.
AB  - OBJECTIVES: To assess patients' preferences about how physicians' deliver news of
      a prostate cancer diagnosis, and patients' preferred participation in medical
      decision-making, with a secondary objective being to validate the Measure of
      Patients' Preferences (MPP) scale with these patients. PATIENTS AND METHODS:
      Eighty-seven men (mean age 62.4 years) referred to an ultrasound/radiology
      department for their first transrectal ultrasonography (TRUS)-guided biopsy
      completed the MPP and Control Preferences measures. Patients were asked to
      identify how they would like to be told about a potential prostate cancer
      diagnosis by their physician, and what role they would like in making treatment
      related decisions with their physicians. RESULTS: Most patients wanted either an
      active (43%) or collaborative (47%) role in medical decision-making if the TRUS
      showed prostate cancer. Men rated content items (what and how much information is
      provided by their physician) as more important than supportive (emotional support
      during interaction) or facilitative (setting and context variables) items. Men
      who preferred a collaborative role in the patient-physician interaction wanted
      significantly (P = 0.04) more content (detailed information on available
      treatments and the effect of these treatments on their quality of life) than men
      who had a preference for either an active or passive role in medical decision
      making. Demographic characteristics were not indicative of either preferred role
      in decision-making or communication preferences. The MPP was shown to be
      reliable. CONCLUSIONS: Men have expectations about how physicians disclose a
      diagnosis of prostate cancer and how they wish to participate in making treatment
      decisions. These results underline the importance of identifying patient
      preferences before embarking on treatment discussions, as the way 'bad news' is
      disclosed has previously been identified as a predictor of the outcome of the
      patient-physician interview.

PMID- 14678367
TI  - A randomized trial of choice of treatment in prostate cancer: the effect of
      intervention on the treatment chosen.
AB  - OBJECTIVE: To determine whether different approaches in the choice of treatment
      affect the treatment chosen by the patient for prostate cancer. PATIENTS AND
      METHODS: We conducted a randomized trial with 210 men who had a histologically
      confirmed diagnosis of prostate cancer in 1993-94 at four major hospitals in
      Finland. After obtaining informed consent the men were randomized either to an
      intervention arm, in which there was greater patient participation in the choice
      of treatment following a structured procedure, or a control arm in which the
      standard approach, i.e. a standardized treatment protocol, was used. The main
      outcome measure of the analysis was the primary treatment chosen for prostate
      cancer. RESULTS: In the enhanced participation arm patients not eligible for
      radical prostatectomy chose orchidectomy less frequently and favoured nonsurgical
      endocrine treatment than in the treatment protocol arm. Radical prostatectomy was
      the most commonly chosen treatment option in both arms among men with operable
      cancer. The way treatment options were presented affected the treatment chosen
      for prostate cancer. CONCLUSION: Patients with prostate cancer are willing and
      able to take an active role in making decisions. The preferences of patients with
      prostate cancer in the choice of treatment may differ from the priorities of the
      physicians.

PMID- 14678368
TI  - Significance of cancer detection in the anterior lateral horn on systematic
      prostate biopsy: the effect on pathological findings of radical prostatectomy
      specimens.
AB  - OBJECTIVE: To clarify the significance of cancer detection in the anterior
      lateral horn (ALH) on systematic prostate biopsy in relation to its effect on the
      pathological findings from retropubic radical prostatectomy (RRP) specimens.
      PATIENTS AND METHODS: The study included 84 consecutive patients who underwent
      RRP at our institution between January 1999 and December 2002, after being
      diagnosed as having prostate cancer, based on systematic prostate biopsies that
      included the areas taken by standard sextant biopsies and the bilateral ALHs.
      Several clinicopathological factors of these patients were analysed in relation
      to the presence or absence of cancer in the ALH on systematic biopsy. RESULTS: Of
      the 84 patients, cancer was detected in the ALH in 44 (group A), but not in the
      remaining 40 (group B). There were no significant differences in age,
      preoperative serum prostate-specific antigen level, or prostate volume between
      the groups. However, the incidence of bilateral positive cores and the percentage
      of positive biopsy cores in group A were significantly higher than those in group
      B. Pathological examinations of RRP specimens showed no significant differences
      in the incidence of lymphatic invasion, vascular invasion and perineural
      invasion, or Gleason score between the groups, but group A had a significantly
      larger tumour volume and higher incidence of extraprostatic disease than group B.
      CONCLUSIONS: Despite similar biological tumour characteristics and irrespective
      of the cancer location in the ALH, advanced and extensive disease frequently
      involves the ALH. Therefore, more aggressive treatment should be considered if
      cancer is detected in the ALH by systematic prostate biopsy.

PMID- 14678369
TI  - T1G3 transitional cell carcinoma of the bladder: recurrence, progression and
      survival.
AB  - OBJECTIVES: To report our experience with T1G3 bladder tumours over the last 10
      years. PATIENTS AND METHODS: We analysed the outcome of 74 consecutive patients
      treated for a T1G3 bladder cancer between 1991 and 2001. Fifty-seven patients
      (77%) were treated with transurethral resection (TUR) plus six weekly
      instillations of bacillus Calmette-Guerin (BCG) therapy. Ten patients (13.5%)
      with contraindications to BCG or with a small T1a tumour were treated with TUR
      plus mitomycin-C, and seven (9.5%) were treated with TUR alone because of their
      age. Patients treated with BCG had systematic biopsies taken at the end of the
      first course. Patients with residual tumour received a second course of six
      weekly instillations. Patients with negative biopsies received maintenance BCG
      therapy consisting of intravesical instillations each week for 3 weeks given 3,
      6, 12, 18, 24, 30 and 36 months after the first course. RESULTS: The median
      follow-up was 53 months. The overall recurrence rate was 46% and the overall
      progression rate 19%. The rate of delayed cystectomy was 8% and that of disease
      specific survival 91%. In patients who received BCG therapy, the recurrence and
      progression rates were 42% and 23%, respectively. In this group the rate of
      disease-specific survival was 88%. CONCLUSION: This study confirms that
      maintenance BCG therapy is an effective treatment for T1G3 bladder tumours, with
      an acceptable rate of bladder preservation.

PMID- 14678370
TI  - Does extended lymphadenectomy increase the morbidity of radical cystectomy?
AB  - OBJECTIVE: To report the events during and after radical cystectomy and urinary
      diversion for bladder cancer, in terms of major and minor complications,
      comparing a minimal with an extended lymphadenectomy, as more lymph nodes
      obtained during radical cystectomy may improve staging and thus the outcome.
      PATIENTS AND METHODS: We reviewed 92 consecutive patients who underwent radical
      cystectomy from March 1998 to February 2002; 46 had a minimal (group A) and 46 an
      extended lymphadenectomy (group B). Cases were selected according to the American
      Society of Anesthesiologists classification, only including those graded 2 or 3.
      We specifically evaluated the incidence and type of complications within 30 days
      after surgery. RESULTS: Because of extending the lymphadenectomy the operative
      duration was a median of 63 min longer in group B (P < 0.01). Complications
      requiring surgical interventions occurred in four (9%) patients in group A and
      five (11%) in group B (P = 0.28). Complications requiring no surgical
      intervention were also similar in both groups. Three patients died, two in group
      A and one in group B (P = 0.57). CONCLUSION: Extended lymphadenectomy in radical
      cystectomy does not increase the morbidity within 30 days of surgery.

PMID- 14678371
TI  - Laparoscopic radical nephrectomy for T1 renal cancer: the gold standard? A
      comparison of laparoscopic vs open nephrectomy.
AB  - OBJECTIVE: To evaluate the complication rate and clinical follow-up of patients
      treated for T1 renal cancer by open or laparoscopic nephrectomy at the same
      institution, as this approach appears to be attractive for treating small renal
      cancers. PATIENTS AND METHODS: Between 1995 and 2002, 39 patients underwent
      retroperitoneal laparoscopic and 26 transperitoneal open radical nephrectomy for
      T1 renal cancer (TNM 1997). Variables before during and after surgery, e.g.
      cancer recurrence, were compared between the groups. RESULTS: There were no
      differences between the laparoscopic and open groups in age, sex ratio, weight,
      height, fitness score, operative duration (134 vs 133 min), minor or major
      complications, tumour diameter, Fuhrman grade or length of follow-up. Patients
      who underwent laparoscopic surgery had less blood loss (133 vs 357 mL, P <
      0.001), less need for transfusion (none vs 150 mL, P = 0.04), a lower consumption
      of analgesia drugs, and shorter hospitalization (5.5 vs 8.8 days, P < 0.001).
      With a mean follow-up of 20.4 months there was no recurrence or tumour
      progression. CONCLUSION: Laparoscopic radical nephrectomy for patients with T1
      renal cancer is a safe, reliable procedure that decreases hospitalization time
      and bleeding, and ensures the same cancer control as open nephrectomy.

PMID- 14678372
TI  - Solifenacin appears effective and well tolerated in patients with symptomatic
      idiopathic detrusor overactivity in a placebo- and tolterodine-controlled phase 2
      dose-finding study.
AB  - OBJECTIVES: To evaluate the dose-response relationship and safety/tolerability of
      solifenacin succinate (YM905) in the treatment of overactive bladder (OAB), and
      to compare its efficacy and safety/tolerability with tolterodine 2 mg twice
      daily. PATIENTS AND METHODS: This multicentre study included a 2-week single
      blind placebo run-in, a 4-week double-blind placebo-controlled active treatment
      phase, and a 2-week follow-up. Men and women with an OAB and urodynamic evidence
      of detrusor overactivity were randomized to placebo or solifenacin 2.5, 5, 10 or
      20 mg once daily, or tolterodine 2 mg twice daily. RESULTS: Of 265 patients
      enrolled, 225 were randomized and 192 completed the study. Solifenacin 5, 10 and
      20 mg produced statistically significant (P < 0.05) improvements in voids/24 h vs
      placebo, whereas tolterodine did not; the mean change with tolterodine was
      between those with solifenacin 2.5 and 5 mg. The outcome was similar for the mean
      change from baseline to endpoint in mean volume voided/void. For incontinence and
      urgency episodes/24 h the solifenacin dose groups showed numerically superior
      changes vs placebo; the mean effects with tolterodine were generally smaller than
      with solifenacin. Most of the efficacy effect of solifenacin was evident at 2
      weeks. Quality-of-life outcomes supported the efficacy results. Solifenacin 5 and
      10 mg were well tolerated; there were no serious treatment-related adverse
      events. The incidence of dry mouth was 14% for solifenacin 5 and 10 mg, 2.6% for
      placebo and 24% for tolterodine. CONCLUSION: In this study, the 5- and 10-mg
      doses of solifenacin appeared to be the most clinically effective for treating
      OAB, considering the balance between efficacy, quality of life and tolerability.
      From the results of this study solifenacin 5 and 10 mg were selected for further
      evaluation in large-scale phase 3 studies.

PMID- 14678373
TI  - A randomized crossover study to evaluate Ro 115-1240, a selective alpha1A/1L
      adrenoceptor partial agonist in women with stress urinary incontinence.
AB  - OBJECTIVES: To investigate the potential therapeutic benefits of the selective
      alpha1A/1l-adrenoceptor partial agonist Ro 115-1240 in women with mild-to
      moderate stress urinary incontinence (SUI). PATIENTS AND METHODS: Thirty-seven
      women with mild-to-moderate SUI were enrolled in a randomized, placebo-controlled
      crossover study. Patients received 1.5 mg Ro 115-1240 twice daily or matching
      placebo for 2 or 4 weeks. Voiding diaries were used to record the number of SUI
      episodes, urge incontinence episodes and pads used. Sitting blood pressures and
      heart rate were recorded at each visit. RESULTS: Ro 115-1240 was associated with
      a significantly lower mean weekly number of SUI episodes than placebo (8.4 vs
      6.0; P= 0.0079), a 28% relative improvement over placebo. There was also a
      significantly lower mean number of pads used and wet pads changed/week with Ro
      115-1240 than with placebo (P = 0.0055 and 0.0066, respectively). The most
      frequently reported treatment-emergent adverse events were scalp tingling,
      headache, chills, piloerection, and pruritus. Generally these events were
      transient and mild to moderate. There was a slightly lower mean sitting heart
      rate with Ro 115-1240 than with placebo, but no difference in mean systolic or
      diastolic blood pressure between treatments. CONCLUSIONS: This study suggests
      that selective alpha1A/1l-adrenoceptor partial agonists have the potential to
      improve the symptoms of SUI with little or no cardiovascular effect. These
      results are encouraging and a randomized controlled trial of Ro 115-1240 in a
      larger population with SUI is warranted to substantiate these findings.

PMID- 14678374
TI  - Management of acute urinary retention secondary to benign prostatic hyperplasia
      in the UK: a national survey.
AB  - OBJECTIVE: To analyse current practice in the management of acute urinary
      retention (AUR) secondary to benign prostatic hyperplasia (BPH) in the UK, and to
      assess how much of this is evidence-based. METHODS: In all, 410 consultant
      urologists practising in UK hospitals were sent a questionnaire about the
      management of AUR secondary to BPH. Data were collected on practice relating to
      initial management, trial without catheter (TWOC), the use of alpha-blockers and
      the follow-up. The need for a uniform guideline in the management of AUR
      secondary to BPH was also assessed. RESULTS: We received 270 (66%) replies, of
      which six were excluded because they were from subspeciality interests (e.g.
      paediatric urology) or had ambiguous answers; 264 (64%) were therefore available
      for analysis. Urethral catheterization was the initial management of choice
      (98%), failing which a suprapubic catheter was inserted. Two-thirds (65.5%)
      admitted the patient after catheterization. Most consultants initiated alpha
      blockers (70.5%), with 64% (118) of these using a TWOC 2 days after starting
      them. One failed TWOC was an indication for transurethral resection of the
      prostate for 192 (72.8%), with 136 (49.8%) re-admitting the patient for surgery
      later. Routine follow-up after a successful TWOC was advocated by 77.3%. Just
      over half the respondents (52.6%) felt that there was no need for uniform
      guidelines in the management of AUR secondary to BPH. CONCLUSION: This survey
      identified a reasonable national uniformity in managing AUR secondary to BPH in
      the UK, but significant aspects of current practice are not evidence-based.

PMID- 14678375
TI  - Prostaglandin E2 and bethanechol in combination for treating detrusor
      underactivity.
AB  - OBJECTIVE: To test the hypothesis, in a prospective randomized double-blind
      study, that the combination of intravesical prostaglandin E2 (PGE2) and oral
      bethanechol chloride (BC) are additive or synergistic in improving bladder
      emptying, as they have been used alone for treating impaired detrusor
      contractility with little clinical benefit. PATIENTS AND METHODS: Nineteen
      patients with detrusor underactivity (17 men and two women) were eligible and
      randomized to one of two treatments. All had postvoid residual urine volumes
      (PVR) consistently of > 300 mL, most being reliant on clean intermittent self
      catheterization (CISC). The experimental treatment group (nine patients) received
      once-weekly intravesical PGE2 (1.5 mg in 20 mL 0.9% saline) plus BC 50 mg four
      times daily, for a total of 6 weeks. The second group of 10 patients received a
      once-weekly instillation of saline together with placebo tablets, again for 6
      weeks. RESULTS: Before treatment the median (interquartile range) PVR was 426
      (405-480) mL for those receiving both drugs; this decreased to 325 (290-352) mL
      after completing the treatment (P < 0.015). In the placebo group the respective
      values were 576 (539-777) and 538 (350-775) mL (P = 0.09). Four of the patients
      receiving the active combination reported symptomatic improvement and were able
      to reduce the frequency of CISC. CONCLUSION: Although there was evidence of a
      pharmacological effect, BC and PGE2 had a limited therapeutic effect compared
      with placebo. Whilst we would not recommend this treatment as routine, it may be
      considered for the occasional treatment of a patient with detrusor underactivity.

PMID- 14678376
TI  - Acute prostatitis in middle-aged men: a prospective study.
AB  - OBJECTIVES: To determine the clinical outcome of middle-aged men with acute
      prostatitis, the optimum time for re-assessing their prostate-specific antigen
      (PSA) levels, and to detect any possible echotextural and vascular changes that
      remain as a consequence of acute inflammation. PATIENTS AND METHODS: Persistent
      fever prompted a re-evaluation for prostatic abscess formation in 28 middle-aged
      men, using transrectal ultrasonography (TRUS) colour Doppler imaging, undertaken
      at the 3-, 6- and 12-month visits. The results of TRUS were compared with
      laboratory data and clinical outcome. RESULTS: Two abscesses were detected; 19
      (68%) of the patients remained infection-free at the 3-month visit. Serum PSA
      levels were elevated in 11 (39%) of the patients at this visit; three prostate
      carcinomas were diagnosed. Increased intraprostatic colour flow was detected in
      68% and there were hypoechoic areas in 46% of the patients. CONCLUSION: The re
      evaluation for abscess formation should not be postponed for > 48 h. Patients
      with acute prostatitis tend to have persistent infection. PSA levels could be
      high even up to 3 months after an acute episode. Middle-aged men with carcinoma
      could be missed during the acute phase of inflammation. PSA and TRUS monitoring
      are strongly recommended.

PMID- 14678377
TI  - The impact of sildenafil citrate on sexual satisfaction profiles in men with a
      penile prosthesis in situ.
AB  - OBJECTIVE: To assess the efficacy of sildenafil in increasing penile glans
      tumescence and improving patient satisfaction in men with a penile prosthesis, as
      this remains a major treatment for erectile dysfunction but a common complaint is
      the lack of glans engorgement. PATIENTS AND METHODS: To determine whether
      sildenafil combined with a penile prosthesis improves satisfaction, patients used
      an implant alone for at least 1 month, after which they completed the
      International Index of Erectile Function (IIEF) questionnaire. The same patients
      were then given sildenafil citrate and completed the IIEF questionnaire after
      using the sildenafil/implant combination. RESULTS: Patients who responded to
      sildenafil with glans engorgement reported significantly greater satisfaction
      scores than with an implant alone. CONCLUSION: We currently offer sildenafil
      citrate after implantation to all men who have a penile prosthesis placed.

PMID- 14678378
TI  - Apomorphine sublingual as primary or secondary treatment for erectile dysfunction
      in patients with spinal cord injury.
AB  - OBJECTIVES: To evaluate the effectiveness of apomorphine sublingual (SL) 3 mg, as
      a primary or secondary treatment for erectile dysfunction (ED) in patients with
      spinal cord injury (SCI), and to determine possible differences in efficacy
      considering clinical, urodynamic and neurophysiological findings. PATIENTS AND
      METHODS: The study included 22 patients with chronic SCI and neurogenic ED who
      were examined physically and by a video-urodynamic evaluation. A
      neurophysiological evaluation included somatosensory evoked potentials of the
      pudendal nerve, palmar and plantar sympathetic skin responses and bulbocavernous
      reflex recordings. Thereafter the patients received 8 tablets of apomorphine SL 3
      mg and were asked to complete the International Index of Erectile Function
      questionnaire before and after treatment. Side-effects, subjective efficacy
      compared with other treatments and satisfaction with the SL administration were
      recorded. RESULTS: Of the 22 men, 11 had upper motor neurone lesions (six
      complete, five incomplete), eight lower motor neurone lesions (seven complete,
      one incomplete) and three had mixed lesions. In all, 12 patients took sildenafil
      citrate and five alprostadil intracavernosally beforehand, and five had used
      nothing to treat their ED. Seven patients had some response and reported that the
      drug helped them to obtain an erection, but only two reported erections
      sufficient for intercourse and would agree to continue apomorphine SL as their
      standard treatment; all the others reported being disappointed. Nine patients
      reported side-effects. There were no significant correlations for
      electrophysiological or urodynamic findings and treatment success. Of the 22
      patients 20 preferred SL rather than the normal administration. CONCLUSIONS:
      Apomorphine SL, a D1/D2 dopamine agonist, facilitates erectile function in a
      heterogeneous group of patients with no significant relationship with any of the
      assessed urodynamic or electrophysiological variables. The overall low rates of
      response either for primary or secondary treatment suggests that apomorphine will
      have limited applicability in patients with SCI.

PMID- 14678379
TI  - Treatment of penile curvature with Essed-Schroder tunical plication: aspects of
      quality of life from the patients' perspective.
AB  - OBJECTIVES: To investigate retrospectively the long-term functional results and
      quality of life of patients undergoing the Essed-Schroder procedure (a simple
      plication of the tunica albuginea) to correct penile deviation, using a
      standardized questionnaire. PATIENTS AND METHODS: Between 1998 and 2001, 59
      patients had surgery in our hospital to correct penile deviation (mean age 40
      years at the time of surgery; mean follow-up 30 months for this study). All 59
      patients received a standardized questionnaire via mail, of which 50 could be
      assessed as valid. RESULTS: Of the 50 patients, 22 had a congenital penile
      deviation and 28 Peyronie's disease. In all patients the penis was completely
      straightened. The proportion of patients capable of sexual intercourse was
      significantly higher after surgery (90%) than before (62%). The frequency of pain
      during intercourse was halved. Of the 50 patients, 60% would have the same
      operation again, 32% were undecided and 8% would not; 22% were dissatisfied with
      the results. None of the patients had complete erectile dysfunction after
      surgery; 74% reported a decrease in penile length and 78% of the patients'
      partners were satisfied with the outcome. CONCLUSIONS: The tunical plication
      procedure is simple and minimally invasive for correcting penile deviation. In
      the opinion of most patients the Essed-Schroder method provides a significant
      improvement in sexual function and quality of life with maximum protection of
      erectile function.

PMID- 14678380
TI  - Exaggerated primary endoscope deflection: initial clinical experience with
      prototype flexible ureteroscopes.
AB  - OBJECTIVE: To increase the clinical usefulness of the actively deflectable
      flexible ureteroscope by making sequential changes in design and then using these
      prototypes clinically; and to develop a clinical series using the optimum
      prototype and contrast it with an extensive database of patients treated with the
      traditional flexible ureteroscope. METHODS: A series of prototypic flexible
      ureteroscopes was developed and used clinically. The active deflection of the
      prototype ureteroscope was evaluated with and with no accessories in the working
      channel, and compared with a standard 7.5 F ureteroscope. Clinical data were then
      accrued and compared with a previously published database. RESULTS: The
      progression of prototypes led to a final version which incorporated > 300 degrees
      primary active deflection, shaft miniaturization (8.4 F) and an increase in
      endoscope shaft stiffness. The prototype flexible ureteroscope had significantly
      greater active deflection than the standard ureteroscope, especially when working
      channel accessories were used. In all, 115 endoscopic procedures were carried
      out, the indications for which included endoscopic lithotripsy for distal calculi
      (51), treatment of upper tract urothelial carcinoma (27), diagnostic endoscopy
      (26) and retrograde endopyelotomy (three). No guidewire was required to place the
      flexible ureteroscope into the upper urinary tract in 27% of patients. Active
      intramural dilatation for access was only required in 3% of the procedures. All
      lower pole calyces were accessed with this instrument. CONCLUSIONS: Adding
      exaggerated deflection is a timely advance in flexible ureteropyeloscopy. This
      and the other changes in design facilitated complex retrograde endoscopic
      procedures and increased the therapeutic potential of the instrument.

PMID- 14678381
TI  - Are new-generation flexible ureteroscopes better than their predecessors?
AB  - OBJECTIVE: To compare two newly designed flexible ureteroscopes with their
      respective predecessors, to determine whether design advances have overcome the
      limitation of tip deflection, which may interfere with diagnosis and treatment of
      lower pole renal pathology. MATERIALS AND METHODS: Two new-generation flexible
      ureteroscopes, the DUR-8 Elite (ACMI, Southborough, MA, USA) and 11278AU (Karl
      Storz Endoscopy, Culver City, CA, USA) were compared with their previous models,
      the ACMI DUR-8 and the Storz 11274AAU. Active tip deflection and irrigation flow
      rates with and without various endoscopic tools were assessed. Specifications,
      purchase prices and repair costs were obtained from each manufacturer. The field
      of view and screen image size of each ureteroscope were also compared. RESULTS:
      The ACMI DUR-8 Elite and the Storz 11278AU had improvements of 79 degrees and 144
      degrees, respectively, from their respective older models. Although the tip
      deflection of all ureteroscopes was compromised by inserting different endoscopic
      tools, these new instruments were less affected. With a 3 F basket inside the
      working channel, the ACMI DUR-8 Elite and the Storz 11278AU had only 0.7% and
      2.8% loss of upward tip deflection, compared with their older models, at 9.6% and
      5.0%, respectively. However, the flow rates of these new instruments were
      decreased. CONCLUSION: The new flexible ureteroscopes have significantly better
      active tip deflection than previous models, both with and without endoscopic
      instrumentation inserted. However, improved flexibility is at the expense of
      decreased flow rates and higher purchase costs.

PMID- 14678382
TI  - Metabolic risk factors in patients with renal stones in KwaZulu Natal: an inter
      racial study (Asian and Whites).
AB  - OBJECTIVE: To identify any differences between Whites and Indians in KwaZulu
      Natal province, South Africa, in the metabolic risk factors which predispose them
      to urinary stone formation. PATIENTS AND METHODS: Urinary stone disease is often
      a manifestation of an underlying metabolic disorder in most patients. Intrinsic
      and extrinsic factors affect the susceptibility of an individual to develop
      urinary stones. Although South African-born Indians and Whites in KwaZulu Natal
      share some of the same extrinsic factors, diet and genetic factors differ between
      the groups. In a study from April 1999 until April 2001, 140 patients were
      included who had a radiological diagnosis of renal calculi; they were evaluated
      metabolically using previously recommended methods. RESULTS: All the patients had
      at least one identifiable metabolic risk factor; the prevalence of the common
      metabolic risk factors was similar in the two groups. The prevalence of complete
      renal tubular acidosis (type 1) was significantly higher in the Indian patients.
      The most common metabolic abnormalities were hypomagnesuria and hypocitraturia,
      followed by low urinary volume. Hypercalciuria was not significant in this
      population. While Indians had lower urine volumes than Whites, Whites had
      significantly higher urinary calcium excretion than Indians. CONCLUSION: There
      were a few variations in the metabolic risk factors between Indians and Whites,
      and the differences could be attributed to genetic or dietary habits. The high
      incidence of renal tubular acidosis in Indian patients could explain the higher
      prevalence of urinary stone disease in this group than in other racial groups.

PMID- 14678383
TI  - Rhabdomyosarcoma of the bladder, prostate or vagina: the role of surgery.
AB  - OBJECTIVE: To retrospectively analyse the outcome of children with
      rhabdomyosarcoma (RMS) of the bladder, prostate or vagina who were treated with
      chemotherapy, with or without radical surgery or additional radiotherapy, at our
      institution since 1968. PATIENTS AND METHODS: From a total of 107 children with
      RMS seen between 1968 and December 2001, 22 (mean age 5.9, range 0.5-18) had RMS
      of bladder/prostate or vagina. Twenty of the patients received primary
      polychemotherapy (vincristine, actinomycin D, cyclophosphamide, adriamycin, and
      more recently including etoposide and ifosfamide), two had primary surgery and
      seven had additional radiotherapy. Fourteen patients had radical
      cystoprostatectomy, with continent cutaneous urinary diversion with an ileocaecal
      pouch in seven, in one each a transverse colonic pouch, orthotopic ileocaecal
      bladder substitution, a rectal reservoir and rectosigmoid pouch and a colonic
      conduit diversion in two patients. RESULTS: After a mean (range) follow-up of 8.6
      (1.0-26) years, 17 patients had no evidence of disease. Five patients presenting
      initially with advanced tumour stages died from progressive RMS. Two patients
      with a continent urinary diversion required ureteric reimplantation for stenosis.
      In two patients severe bladder contraction after radiotherapy required bladder
      augmentation. CONCLUSION: Primary chemotherapy followed by radical surgery of RMS
      of the prostate and/or bladder allows complete tumour resection in most cases,
      and yields excellent cure rates.

PMID- 14678384
TI  - A comparison of palpable and impalpable cryptorchid testes using CD-99
      immunohistochemistry.
AB  - OBJECTIVE: To compare the clinical and morphological features of impalpable and
      palpable cryptorchid testes, as there is debate about how much effort is
      appropriate to bring an impalpable undescended testicle into the scrotum.
      PATIENTS AND METHODS: We reviewed retrospectively 189 cases of undescended
      testicles in 168 patients who were explored surgically by one surgeon between
      August 1997 and September 2000. Operative findings of palpability, testicular
      size and location were collected. The mean tubular diameter (MTD), tubular
      fertility index (TFI) and mean number of germ cells per tubule (MGCT) were
      calculated using immunohistochemistry for CD-99, a Sertoli-cell marker, to
      classify germ cells more accurately. RESULTS: Sixty-three testes (33%) were
      impalpable; the median age at the time of surgical exploration was 23 months for
      both groups. The mean (sd) testicular volume for the impalpable and palpable
      groups were 0.83 (0.38) and 1.22 (0.54) mL, respectively. Using fitted curves of
      size vs age, impalpable testes were smaller than palpable testes at all ages,
      with the difference nearly statistically significant (P < 0.06). The MTD, TFI and
      MGCT decreased with age in both groups, with no statistically significant
      differences between the groups. A sub-analysis of abdominal and extra-abdominal
      testes confirmed no significant differences. CONCLUSION: Impalpable testes are
      smaller at the time of exploration than palpable cryptorchid testes. However,
      histological factors predict that impalpable testes have a significant chance of
      future fertility and therefore orchidopexy is appropriate. CD-99
      immunohistochemistry makes objective morphological information easier to obtain.

PMID- 14678385
TI  - Genital sensation after feminizing genitoplasty for congenital adrenal
      hyperplasia: a pilot study.
AB  - OBJECTIVE: To assess sensation in the clitoris and vagina in women with
      congenital adrenal hyperplasia (CAH) who have previously had genital surgery, and
      to evaluate sexual function in this group as the latter, and particularly the
      experience of orgasm, appear to be closely related to sensitivity. PATIENTS AND
      METHODS: Six women were recruited from a multidisciplinary clinic specialising in
      intersex conditions, and representing an initial cohort from a larger ongoing
      study. The patients were asked to complete a postal questionnaire with a
      specialized sexual function assessment. Thermal, vibratory and light-touch
      sensory thresholds were assessed in the clitoris and vagina using a genito
      sensory analyser and Von Frey filaments. RESULTS: All six women had highly
      abnormal results for sensation in the clitoris. Only three of them had an
      introitus capable of admitting the vaginal probe, and the vaginal sensory data of
      all three were within the validated ranges. A self-administered sexual function
      assessment was completed by the five women who were sexually active. The scores
      indicated sexual difficulties, particularly in the areas of infrequency of
      intercourse and anorgasmia. CONCLUSIONS: The sensory data for all six women were
      outside the normal range for the clitoris. The results for the upper vagina,
      which had not had surgery, were within normal ranges. These findings suggest that
      genital surgery may disrupt sensory input. Sexual function also appears to be
      impaired and this may relate to the compromised sensitivity and restricted
      introitus. The possibility that women with CAH have deficient clitoral sensation
      ab initio cannot be excluded. These striking findings must be evaluated further
      in the light of the controversy about the issue of genital surgery in children
      with CAH.

PMID- 14678386
TI  - Expanded PTFE bladder neck slings for incontinence in children: the long-term
      outcome.
AB  - OBJECTIVE: To assess the long-term outcome of circumferential expanded PTFE (Gore
      tex, WL Gore Associates, Scotland) bladder neck slings for achieving urethral
      continence in children with a neuropathic bladder. PATIENTS AND METHODS: The
      records were reviewed of 19 children undergoing bladder reconstruction (most with
      a neuropathic bladder) who had a Gore-tex sling placed circumferentially at the
      bladder neck, over a 5-year period. Of these, seven had spina bifida; two each
      spinal dysraphism, surgery for anorectal anomalies and an idiopathic neuropathic
      bladder; five who developed a neuropathic bladder from other causes, and one born
      with bladder exstrophy. All children had an uncompliant bladder with a low
      urethral leak-point pressure on preoperative urodynamics. In all children
      conventional clean intermittent catheterization and pharmacotherapy had failed.
      Four had had previous augmentation surgery while 15 had concomitant bladder
      augmentation and formation of a Mitrofanoff stoma. The main outcome measure was
      achieving dryness. The original intention of the procedure was also to maintain
      urethral catheterization. RESULTS: Full details of the follow-up were available
      in 17 patients. Despite initial good short-term results, at a median follow up of
      7 years, in 14 patients the sling had to be removed because of erosion, often
      with transient urethral leakage before the bladder neck subsequently closed. A
      bladder calculus was associated with each case of erosion except one. CONCLUSION:
      Although in the short term this technique had favourable results, it was not a
      useful technique in the long term.

PMID- 14678387
TI  - The phosphatidylinositol-3 kinase pathway regulates bladder cancer cell invasion.
AB  - OBJECTIVES: To investigate the role of the phosphatidylinositol (PI)-3 kinase
      pathway in the invasion of bladder cancer cell lines, and to assess the
      activation of this pathway in primary human bladder tumours. MATERIALS AND
      METHODS: Human bladder cancer cells were treated with pathway specific inhibitors
      or were transfected with PI-3 kinase pathway components. The invasion of cultured
      bladder cancer cells was analysed by an invasion assay. Bladder cancer cells
      lines and primary human bladder tumours were analysed for pathway activation by
      western blotting. RESULTS: A specific inhibitor of PI-3 kinase enzyme activity,
      Ly294002, potently suppressed the invasive properties of three highly invasive
      bladder tumour cell lines. Restoration of the PTEN gene to invasive UM-UC-3
      bladder tumour cells or expression of a dominant-negative version of the PI-3
      kinase target, Akt, also potently inhibited invasion, indicating a central role
      for the PI-3 kinase/Akt pathway in this process. In addition, 55% of primary
      tumours from patients with bladder cancer had markedly high levels of
      phosphorylated Akt. CONCLUSION: Pharmacological or biochemical inhibition of the
      PI-3 kinase pathway drastically reduced the invasive capacity of bladder cancer
      cell lines; over half of primary human bladder tumours had high Akt
      phosphorylation, suggesting that the aberrant activation of this pathway may
      contribute to the invasion of a significant subset of bladder cancers.

PMID- 14678388
TI  - Expression of CD44 protein in bilharzial and non-bilharzial bladder cancers.
AB  - OBJECTIVES: To investigate the expression of CD44 protein in bilharzial and non
      bilharzial bladder carcinomas, and to relate the results of immunohistochemistry
      to the established prognostic factors, as studies clearly show that altered
      adhesive function of tumour cells is important in the metastatic process and CD44
      is assumed to be critical in the malignant progression of many human tumours.
      PATIENTS AND METHODS: The study included 55 patients with bladder carcinoma
      confirmed by cystoscopy and biopsy. Of the 33 patients with transitional cell
      carcinoma (TCC), 19 were bilharzial and 14 non-bilharzial, and of 22 with
      squamous cell carcinoma (SCC), 12 were bilharzial and 10 non-bilharzial. CD44
      expression was measured by immunohistochemical analysis of paraffin-embedded
      tissue obtained from these patients after appropriate treatment (transurethral
      resection, partial or radical cystectomy). RESULTS: There was significantly less
      CD44 expression in invasive TCC than in normal urothelium and pre-invasive TCC (P
      = 0.05). The expression of CD44 was inversely related to the tumour grade and
      depth of invasion (P = 0.05). However, there was no such relation for SCC; there
      was no significant difference between CD44 expression in metaplastic squamous
      epithelium, pre-invasive and invasive SCC. The presence or absence of bilharzial
      ova had no apparent effect on the expression of CD44, with no significant
      difference between CD44 expression in bilharzial and non-bilharzial bladder
      carcinomas. CONCLUSIONS: These data confirm that there is a reduction in CD44
      expression with increasing tumour grade and stage of TCC, and may provide an
      additional aid in predicting the progression of this tumour. There was no such
      relationship with SCC, and no difference between CD44 expression in bilharzial
      and non-bilharzial bladder carcinomas.

PMID- 14678389
TI  - Investigation of sequential mitomycin C and photodynamic therapy in a mitomycin
      resistant bladder cancer cell-line model.
AB  - OBJECTIVES: To investigate the hypothesis that sequential mitomycin C and 5
      aminolaevulinic acid (ALA)-mediated photodynamic therapy (PDT) interact
      additively in both the J82 bladder cancer cell line and its mitomycin-C-resistant
      derivative, J82/MMC, and to assess the theoretical basis of this interaction by
      measuring the relative mitochondrial density of the respective cell lines, on the
      basis that the mitochondria are the intracellular site where ALA is metabolized
      to the active photosensitizer, protoporphyrin IX. MATERIALS AND METHODS: Cell
      survival was assayed in J82 cell line and the J82/MMC derivative after treating
      them with sequential ALA-mediated PDT and mitomycin C, and with the sequence of
      treatments reversed. Cell survival was estimated using the tetrazolium assay. The
      relative mitochondrial density of the two cell lines was estimated using flow
      cytometry to measure 123rhodamine fluorescence. RESULTS: The effect of sequential
      mitomycin C followed by ALA-mediated PDT enhanced the effect of PDT in both cell
      lines. In J82/MMC this effect was marginally supra-additive. When ALA-mediated
      PDT was administered before mitomycin C, the combined effect was 'sub-additive'.
      123Rhodamine fluorescence was > 10 times greater in J82/MMC than J82, suggesting
      a significantly higher mitochondrial density in the former than the latter.
      CONCLUSION: Mitomycin C appears to enhance ALA-mediated PDT when administered
      first. This appears to be particularly so in J82/MMC. This phenomenon may have
      clinical significance in recurrent superficial bladder cancer.

PMID- 14678391
TI  - The tensile properties of tension-free vaginal tape and cadaveric fascia lata in
      an in vivo rat model.
AB  - OBJECTIVE: To examine the tensile properties (break load and maximum average
      load), after in vivo implantation in a rat animal model, of tension-free vaginal
      tape (TVT) and cadaveric fascia lata (CFL), as pubovaginal slings of these
      materials have become popular for treating stress urinary incontinence. MATERIALS
      AND METHODS: Twenty Sprague-Dawley rats (300-400 g) had 1 x 2 cm strips of
      commercially available TVT and CFL implanted on the right and left anterior
      abdominal wall, respectively. Half of the animals were then killed at 6 weeks and
      the remainder at 12 weeks, after which the strips of TVT and CFL were removed and
      their tensile properties measured using a tensiometer. The tensile strength of
      TVT and CFL strips maintained only in normal saline served as controls. RESULTS:
      The TVT strips had a mean break load of 0.740 kg in the control and only 0.390 kg
      for CFL (P < 0.05). At 6 weeks the TVT material had a mean (sd) maximum average
      load of 0.634 (0.096) kg and a mean break load of 0.589 (0.249) kg, whereas the
      respective values for the CFL were 0.323 (0.198) and 0.167 (0.063) kg (P < 0.05).
      Similarly at 12 weeks, TVT had a greater mean maximum average and break load than
      CFL, at 0.742 (0.052) and 0.274 (0.126), and 0.737 (0.056) and 0.185 (0.128) kg,
      respectively. CONCLUSION: This is the first study to assess the tensile
      properties of the currently used sling materials, TVT and CFL, in an in vivo
      model. TVT has a greater break load and maximum average load than CFL; the
      tensile strength of these materials does not decrease with time.

PMID- 14678390
TI  - Pharmacological characteristics of Ro 115-1240, a selective alpha1A/1L
      adrenoceptor partial agonist: a potential therapy for stress urinary
      incontinence.
AB  - OBJECTIVE: To describe the preclinical pharmacology of Ro 115-1240, a
      peripherally acting selective alpha1A/1L-adrenoceptor (AR) partial agonist,
      compared with the alpha1A/1L-AR full agonist amidephrine, as AR agonists have
      some utility in the treatment of stress urinary incontinence (SUI) but are
      limited by undesirable cardiovascular and central nervous system side-effects.
      RESULTS: In radioligand-binding studies Ro 115-1240 had greater affinity for
      alpha1A than for alpha1B and alpha1D subtypes. The potency and intrinsic activity
      of amidephrine and Ro 115-1240 relative to noradrenaline were determined in
      native and cell-based assays using human recombinant alpha1-ARs; they acted as
      selective alpha1A/1L-AR full and partial agonists, respectively. In anaesthetized
      micropigs and rabbits, amidephrine and Ro 115-1240 produced non-selective, dose
      dependent increases in intraurethral and arterial blood pressures but the
      magnitude of the pressure increases evoked by Ro 115-1240 were about a third of
      those with amidephrine. In conscious micropigs both agents produced dose
      dependent increases in urethral tension. Again, the magnitude of the urethral
      response to Ro 115-1240 was about a third of that with amidephrine. More
      importantly, only amidephrine produced dose-dependent increases in blood pressure
      and decreases in heart rate. Ro 115-1240 produced a maximum increase in urethral
      tension with no effect on blood pressure or heart rate. CONCLUSION: These results
      show that by combining selectivity for the alpha1A/1L-AR subtype with a reduction
      in intrinsic agonist efficacy, Ro 115-1240 has reduced haemodynamic effects while
      retaining to some degree the contractile effects on urethral smooth muscle. These
      studies indicate that Ro 115-1240 may be useful as a novel treatment for SUI.

PMID- 14678392
TI  - Let's hope for more in 2004.

PMID- 14678393
TI  - Silicon headrests are ideal lithotomy restraints for neonatal and infant
      cystoscopy.

PMID- 14678394
TI  - Testicular prostheses: a new technique for insertion.

PMID- 14678395
TI  - Sexual factors and prostate cancer.

PMID- 14678396
TI  - Improvement in urinary symptoms after radical prostatectomy: a prospective
      evaluation of flow rates and symptom scores.

PMID- 14678397
TI  - A novel method for laparoscopic placement of Tenckhoff peritoneal dialysis
      catheters.

PMID- 14678398
TI  - The role of transarterial embolization in the treatment of renal cell carcinoma.

PMID- 14678399
TI  - Does delaying pyeloplasty affect renal function in children with prenatal
      diagnosis of pelvi-ureteric junction obstruction?

PMID- 14678400
TI  - Orthotopic ileal neobladder.

PMID- 14678405
TI  - The future of primary care in Australia.

PMID- 14678406
TI  - Willing hands at Hualien.

PMID- 14678407
TI  - Patient views on the management of rheumatic fever and rheumatic heart disease in
      the Kimberley: a qualitative study.
AB  - OBJECTIVE: To describe, from a patient perspective, factors leading to suboptimal
      management of individuals with rheumatic fever (RF) and rheumatic heart disease
      (RHD) among members of the Kimberley population. METHOD: Qualitative in-depth
      semistructured and repeated interviews of seven Kimberley patients, or parents of
      children, with rheumatic fever and/or rheumatic heart disease, during 1998.
      RESULTS: Participants showed variable levels of understanding about RF/RHD, often
      relating to the need for secondary prophylaxis. Compliance with medication was
      closely linked with positive patient-staff interactions. From the perspective of
      health care, living in a remote location was frequently described as a negative
      influence. Participants desire more accessible and culturally appropriate
      opportunities for learning about their disease. CONCLUSIONS: Participants focused
      on issues closely related to effective and ineffective management of RF/RHD. The
      lessons learned are indicators for health staff attempting to improve the quality
      of management that people receive.

PMID- 14678408
TI  - Congestive cardiac failure: urban and rural perspectives in Victoria.
AB  - OBJECTIVE: Effective and timely care for congestive cardiac failure (CCF) should
      reduce the risks of hospitalisation. The purpose of this study is to describe
      variations in rates of hospital admissions for CCF in Victoria as an indicator of
      the adequacy of primary care services. Detailed analyses identify trends in
      hospitalisations, urban/rural differentials and variations by the Primary Care
      Partnerships (PCP). SETTING: Acute care hospitals in Victoria. DESIGN: Routine
      analyses of age and sex standardised admission rates of CCF in Victoria using the
      Victorian Admitted Episodes Dataset from 1993-1994 to 2000-2001. SUBJECTS: All
      patients admitted to acute care hospitals in Victoria with the principal
      diagnosis of CCF between 1993-1994 and 2000-2001. RESULTS: There were 8359
      admissions for CCF in Victoria with an average of 7.37 bed days in 2000-2001.
      There was a significantly higher admission rate for CCF in rural areas compared
      to metropolitan in 2000/200--(2.53/1000 (2.44-2.62) and 1.80/1000 (1.75-1.85))-
      respectively. Small area analyses identified 17 PCP (14 of which were rural) with
      significantly higher admission rate ratios of CCF compared to Victoria.
      CONCLUSION: Small area analyses of CCF have identified significant gaps in the
      management of CCF in the community. This may be a reflection of deficit in
      primary care availability, accessibility, or appropriateness. Detailed studies
      may be needed to determine the relative importance of these factors in Victoria
      for targeting specific interventions at the PCP level.

PMID- 14678409
TI  - Taking primary care continuing professional education to rural areas: lessons
      from the United Arab Emirates.
AB  - OBJECTIVE: To assess the impact of a practice based multidisciplinary educational
      program. DESIGN: A descriptive account of experiences in introducing a new
      program of continuing professional development. SETTING: Rural primary health
      care centres in the United Arab Emirates. SUBJECTS: All staff working in the
      rural health centres. RESULTS: The educational intervention proved popular and
      appeared to effect a behavioural change. Teamwork in the health centres showed a
      marked improvement. CONCLUSION: A practice-based, multidisciplinary educational
      program using case-based learning proved to be effective when introduced to rural
      health centres of a developing country with multiracial health care
      professionals. .

PMID- 14678410
TI  - Rural doctors and rural backgrounds: how strong is the evidence? A systematic
      review.
AB  - OBJECTIVE: We sought to summarise the evidence for an association between rural
      background and rural practice by systematically reviewing the national and
      international published reports. DESIGN: A systematic review. SETTING: A search
      of the national and international published reports from 1973 to October 2001.
      SUBJECT: The search criteria included observational studies of a case-control or
      cohort design making a clear and quantitative comparison between current rural
      and urban doctors, this resulted in the identification of 141 studies for
      potential inclusion. RESULTS: We systematically reviewed 12 studies. Rural
      background was associated with rural practice in 10 of the 12 studies, in which
      it was reported, with most odds ratios (OR) approximately 2-2.5. Rural schooling
      was associated with rural practice in all 5 studies that reported on it, with
      most OR approximately 2.0. Having a rural partner was associated with rural
      practice in 3 of the 4 studies reporting on it, with OR approximately 3.0. Rural
      undergraduate training was associated with rural practice in 4 of 5 studies, with
      most OR approximately 2.0. Rural postgraduate training was associated with rural
      practice in 1 of 2 studies, with rural doctors reporting rural training about 2.5
      times more often. CONCLUSIONS: There is consistent evidence that the likelihood
      of working in rural practice is approximately twice greater among doctors with a
      rural background. There is a smaller body of evidence in support of the other
      rural factors studied, and the strength of association is similar to that for
      rural background.

PMID- 14678411
TI  - Indigenous men taking their rightful place in society? A follow up report.

PMID- 14678412
TI  - Role of multi-purpose service programs providing residential aged care in rural
      Australia: a discussion paper.
AB  - OBJECTIVE: To determine if multi-purpose service (MPS) Programs deliver improved
      residential aged care as opposed to traditional rural hospitals. DESIGN: A
      variation on comparative-experimentalist: type 4. In this design 2 groups
      providing different service models of rural health services are compared.
      SETTING: Six MPS Programs and three traditional hospitals in rural New South
      Wales. SUBJECTS: Key stakeholders--area representatives, health service managers,
      MPS managers, doctors, staff, MPS or hospital committee members and consumer
      groups including residents. MAIN OUTCOME MEASURE: To analyse the ability of MPS
      Programs to deliver quality residential aged care as opposed to using traditional
      hospitals for such services. RESULTS: Multi-purpose service programs provided
      better residential environments and greater flexibility of service provision.
      There were few apparent differences between the two service models in regard to
      organisational culture and training. CONCLUSIONS: The findings of this evaluation
      suggest that in the provision of residential aged care in rural communities, MPS
      Programs demonstrated better standards of care than traditional hospital based
      services.

PMID- 14678418
TI  - From society to federation: international collaboration in artificial organs
      research.

PMID- 14678413
TI  - Farm-related injury presenting to an Australian base hospital.
AB  - OBJECTIVE: Data concerning farm-related injuries were collected from the
      Emergency Department at Tamworth Base Hospital over a 12-month period from 1
      September 1997. AIM OF STUDY: The aim of the study was to collect information at
      a local level to establish baselines with a view to developing prevention
      strategies. All people who presented with a farm injury or illness to the
      emergency department participated in the study. RESULTS: During this period there
      were 384 injuries, of which nearly three-quarters were males (72.2%). Four
      injuries were fatal. The average rate of injury per 100 farms per annum in the
      service area of the Hospital was 30 per 100 farms (range 9-80 per 100 farms, per
      annum). Half (54.1%) of the people injured were employed at the time of the
      injury. Horses (21.1%) and motorcycles (15.8%) were the two most common injury
      agents. CONCLUSION: The information gained can be used to direct injury
      prevention at a local level and may be also used at the national level as a guide
      when grouped with other similar studies of different commodity groups.

PMID- 14678419
TI  - The influence of intraperitoneal transplantation of free and encapsulated
      Langerhans islets on the second set phenomenon.
AB  - To protect the allografts or xenografts against transplant rejection special
      semipermeable membranes are applied. So far, there are only a few studies on the
      influence of an immunoisolated graft on the recipient immune system. Therefore,
      the possibility that an intraperitoneally grafted alginate/poly L-lysine/alginate
      (APA) coated pancreatic islets graft can effectively sensitize the recipient and
      provoke second set phenomenon was studied. C3H male mice and male WAG rats were
      used as donors of full-thickness skin and of free or encapsulated islet
      intraperitoneal grafts. Male BALB/c mice served as recipients. Skin grafts were
      performed following the method of Billingham and Medawar. The length of the
      second skin graft survival time served as the criterion for the sensitizing
      capacity of the primary graft. APA encapsulation of islets delayed but has not
      prevented the development of the second set phenomenon. However, the second skin
      graft rejection time was significantly longer after grafting of encapsulated
      islets than after free islets transplantation. APA microencapsulation of
      intraperitoneally transplanted islets delayed but did not prevent the development
      of the second set phenomenon. Encapsulation does not ensure complete
      immunoisolation, but only creates "an artificially immunoprivileged site of
      transplantation."

PMID- 14678420
TI  - Improved retention of endothelial cells seeded on polyurethane small-diameter
      vascular grafts modified by a recombinant RGD-containing protein.
AB  - Sponge-type small-diameter vascular grafts were fabricated from a medical-grade
      polyurethane, Pellethane 2363-80A, by utilization of a salt casting technique.
      The grafts were compliance matched with a storage modulus of 0.53 +/- 0.08 MPa.
      The luminal surface of grafts was modified with a thin layer ( approximately 40
      micro m) of gelatin crosslinked by epoxide. Then a special Arg-Gly-Asp (RGD)
      containing recombinant protein, named CBD-RGD (cellulose binding domain RGD
      containing protein), was coated onto the gelatin layer. The platelet adhesion and
      activation on such a gelatin/CBD-RGD modified surface was significantly reduced.
      Human umbilical vein endothelial cells were seeded more efficiently onto the
      modified grafts. There was also a substantial reduction in the subsequent loss of
      cells from the graft surface following perfusion in vitro. The cell number
      retained on the modified graft was enhanced by three times after 1 h of
      perfusion, and by eight times after 3 h of perfusion (retention rate
      approximately 63%). The retention after 3 h of perfusion could be further
      increased to nearly 100% if the lined endothelium on gelatin/CBD-RGD modified
      graft was cultured for another week before perfusion. The modified surface was
      also shown to help canine external jugular vein endothelial cells to maintain the
      round cell morphology in vitro.

PMID- 14678421
TI  - Development of a nerve scaffold using a tendon chitosan tube.
AB  - Bridge grafting (15 mm) into the sciatic nerve of SD rats was carried out using
      tendon chitosan tubes having either a circular or triangular cross-section, as
      well as triangular tubes combined with laminin, CDPGYIGSR, or CSRARKQAASIKVAVSAD
      (n = 15 in each group). As a control, isografting (15 mm) was carried out in the
      SD rats (n = 7). Specimens were taken after 1, 2, 4, 6, and 8 weeks for
      histology, and nerve regeneration was evaluated electro-physiologically and
      histologically after 12 weeks. The mechanical strength of triangular tubes was
      found to be higher than circular tubes, and the inner volume of a triangular tube
      tends to be larger than in circular tubes. Nerve tissue regeneration along the
      tube wall was found in both the laminin and laminin peptide groups. According to
      the result of percentage neural tissue in relation to evoked action potentials,
      the consecutive treatments of YIGSR and IKVAV was found to match the
      effectiveness of intact laminin.

PMID- 14678422
TI  - Hemolysis in an electromechanical driven pulsatile total artificial heart.
AB  - A motor rotation in an electromechanically-driven pulsatile total artificial
      heart (TAH) may influence hemolysis. This study is designed to evaluate motor
      rotational conditions of the TAH and choose a suitable condition to obtain the
      least hemolytic characteristics. The TAH was driven in two motor rotational
      conditions: a constant motor rotational speed (rpm) mode (mode A) and a gradually
      increasing rpm mode (mode B). In these two modes, a maximum dP/dt value and a
      degree of hemolysis were measured and compared. The TAH was connected to an in
      vitro testing loop. In each mode, the TAH was driven with a fixed pumping rate of
      100 bpm. A preload and an afterload were held at 15 and 100 mm Hg, respectively.
      The outflow of the TAH was maintained at 4.0 L/min. The maximum dP/dt in mode A
      and mode B was 5914 +/- 405 mm Hg/s and 2953 +/- 191 mm Hg/s, respectively. The
      NIH value obtained from mode A and mode B was 0.063 +/- 0.005 g/100 L and 0.026
      +/- 0.003 g/100 L, respectively. The results demonstrated that the TAH driven in
      a gradually increasing rpm mode reduces both a maximum dP/dt value and a degree
      of hemolysis. The gradually increasing rpm mode is a suitable driving condition
      to obtain the least hemolytic characteristics.

PMID- 14678423
TI  - Unloading effect of a rotary blood pump assessed by mathematical modeling.
AB  - Due to the increased appeal of rotary blood pumps for long-term cardiac assist,
      we conducted a study of their capacity to unload the left ventricle (LV). We used
      a validated mathematical model of the cardiovascular system and implemented the
      pump characteristics of an investigational microdiagonal pump (Medos). The
      influence of the pump on systemic hemodynamics, LV energetic parameters, and wall
      stress was evaluated in continuous and synchronous pulsatile modes of operation.
      For the continuous mode simulations, the influence of heart rate, LV
      contractility, and pump speed was assessed in a parametric study. For the
      pulsatile mode, different onsets of a synchronous time-varying pump speed pattern
      were tested. Our data indicate that the effectiveness of unloading in continuous
      mode depends on the contractility of the native ventricle. Hypocontractile
      ventricles are most easily unloaded, while ventricles with moderate contractility
      require high continuous pump speeds to achieve notable unloading. In pulsatile
      mode, the pump timing is an important determinant of pump/cardiovascular system
      interaction, with a counterpulsation setting yielding the best unloading.

PMID- 14678424
TI  - Diaphragm motion affects flow patterns in an artificial heart.
AB  - In the sac-driven artificial heart, the flow characteristics are coupled to the
      dynamics of the sac motion. The opening dynamics of the sac wall can, for
      example, strongly affect the chamber flow characteristics during diastole by
      directing or impeding the inflow. Poor sac motion can reduce the volume output of
      the pump and may increase the potential for thrombus formation within the
      ventricular chamber. It is particularly important for laboratory studies of the
      flow fields in artificial hearts that the diaphragm motion properly simulates the
      sac motion observed in vivo. In the present study, flow visualization was
      performed to investigate the relationship between the chamber flow
      characteristics of a Penn State artificial heart and the motion of the diaphragm
      during the filling phase during in vitro experimentation. The chamber flow
      pattern and diaphragm motion were recorded as a function of time, using high
      speed videography. Experiments were conducted to determine the influence of
      diaphragm motion on the flow characteristics by altering the filling pressure,
      diaphragm thickness, and fluid density. Diaphragm motion was quantified by
      tracking the position of three surface points over the cardiac cycle. The
      alignment of these three surface trajectories can be used to quantify the
      uniformity of diaphragm motion. As a result, diaphragm motion was determined to
      be nonuniform under most operating conditions with the diaphragm opening in a
      wave-like pattern starting at the bottom of the chamber and propagating toward
      the inflow/outflow ports. This opening pattern simulates the opening pattern
      observed in an in vitro study of the clinical blood sac used in the Lionheart
      LVAD.

PMID- 14678425
TI  - Priming Reduced Extracorporeal Circulation Setup (PRECiSe) with the DeltaStream
      diagonal pump.
AB  - Different systems for beating heart procedures and low priming systems limited to
      coronary artery bypass grafting (CABG) have been introduced. We describe Priming
      Reduced Extracorporeal Circulation Setup (PRECiSe), a new low priming system
      which sup-plies all the features of cardiopulmonary bypass (CPB). PRECiSe
      incorporates the DeltaStream diagonal pump, which pumps blood from the right
      atrium to the aorta via a membrane oxygenator and a filter; the system is placed
      beneath the patient's head resulting in extremely short tubing. A reservoir
      allows the use of suckers and vents. Autologous blood priming furthers reduces
      hemodilution. In a safety study the system was used for extracorporeal
      circulation in 11 patients undergoing CABG without adverse effects. By use of
      PRECiSe mean priming was reduced to 268.5 ml resulting in minimal hemo-dilution
      and transfusion requirements.

PMID- 14678426
TI  - Efficacy and safety of a new whole-blood low-density lipoprotein apheresis system
      (Liposorber D) in severe hypercholesterolemia.
AB  - Low-density lipoprotein (LDL) apheresis is an extracorporeal modality to lower
      LDL cholesterol. While most of the devices eliminate LDL particles from plasma, a
      recently introduced whole-blood perfusion column (DALI) adsorbs lipoproteins
      directly from whole blood. We investigated the efficacy and safety of a new whole
      blood LDL apheresis system (Liposorber D) in 10 patients with severe
      hypercholesterolemia in a multicenter trial. In 93 LDL aphereses, the mean
      reduction in LDL cholesterol and lipoprotein(a) was 62.2 +/- 11.5% and 55.6 +/-
      16.9%, respectively (P < 0.01). If hemodilution during apheresis was considered,
      the reductions were 58.0 +/- 10.9 and 55.3 +/- 10.9%, respectively (P < 0.01),
      while high-density lipoprotein (HDL) cholesterol did not change significantly.
      Three mild episodes of hypocalcemia and two mild episodes of arterial hypotension
      were observed; however, LDL apheresis could be continued in each case. In
      conclusion, the new whole-blood LDL apheresis with Liposorber D is a safe,
      simple, and useful modality to reduce LDL cholesterol and lipoprotein(a) in
      cardiovascular high-risk patients.

PMID- 14678427
TI  - Vitamin E-coated membrane dialyzer and beta2-microglobulin removal.
AB  - This study was designed to test the removal of beta2-microglobulin (beta2M) in a
      vitamin E-modified membrane. We investigated in vivo the dialyzer (Excebrane,
      series EE, 1.8 m2) with respect to hydraulic permeability (Kuf), maximum
      ultrafiltration rate (UF max), sieving coefficient (Sc), and solute clearances in
      hemodialysis (HD) and in soft hemodiafiltration (HDF). Kuf was 18.4 ml/h/mmHg, UF
      max was 75 ml/min, and Sc for beta2M was 0.45. Clearance values at 400 ml/min of
      Qb in HD were 258 ml/min for urea, 201 ml/min for creatinine, and 135 ml/min for
      phosphate. In soft HDF, clearances were slightly higher. beta2M clearance was 26
      ml/min in HD and 43 ml/min in soft HDF. In conclusion, Excebrane (series EE)
      procures a soft HDF with an amount of substitution fluid in post dilution mode of
      over 60 ml/min. Remarkable small solute clearances were obtained when the blood
      flow was raised to 400 ml/min. A significant reduction of beta2M is demonstrated
      by HDF.

PMID- 14678428
TI  - Effect of hemodiafiltration on pulmonary hemodynamics in endotoxic shock.
AB  - Hemofiltration can improve pulmonary hemodynamics during septic shock. The main
      objective of the study was to determine whether hemodiafiltration (HDF) would
      also have beneficial effects on pulmonary hemodynamics during septic shock. In
      the Endo group, six anesthetized pigs received a 0.5 mg/kg endotoxin infusion
      over 30 min. In the HDF group (n = 6), HDF was started 30 min after the end of
      the endotoxin infusion, while in the Control group (n = 4) they received HDF but
      no endotoxin infusion. Pulmonary hemodynamics were analyzed in detail with a four
      element windkessel model. Although in the Control group, HDF did not alter
      pulmonary hemodynamic parameters, in the HDF group, it was responsible for an
      amplification of the deleterious pulmonary vascular response to endotoxin insult.
      Our results show that HDF must be used cautiously in septic shock since it can
      precipitate right heart failure by increasing pulmonary vascular resistance.

PMID- 14678429
TI  - Endotoxin adsorption of various dialysis membranes: in vitro study.
AB  - Endotoxin (ET) in the dialysate is known to adsorb on dialysis membranes made of
      polyether polymer alloy (PEPA) and polymethylmethacrylate (PMMA). In the present
      study, we investigated the adsorption of ET on dialysis membranes with a focus on
      PEPA membranes and polysulfone (PS) membranes that are extensively used in
      artificial kidneys or as ET-removal filters. In the case of PEPA, the compounding
      of polyvinylpyrrolidone (PVP) was changed, and both a hydrophobic version and a
      hydrophilic version were used on the blood side. For the PS dialysis, commercial
      membranes (APS (Asahi), BSP (Toray), PSN (Fresenius), CLPS (Terumo)) were used.
      Adsorption was evaluated by exposing both sides of the membrane after it had been
      primed with physiological saline: the ET concentration on the blood side and
      dialysate side of the dialysis membrane was monitored during the 240 min from the
      start of the exposure. When the PEPA membrane was investigated, ET was
      significantly adsorbed on the hydrophobic version. For PS membranes, ET was
      adsorbed on the blood side or on both the blood and dialysate sides, depending on
      the membrane. PS dialysis membranes can adsorb ET but the power and site of
      adsorption are different even between membranes made of the same material. In
      addition to electrostatic action attributable to the compounding of hydrophilic
      agent PVP on the dialysis membrane, the distribution of PVP that was compounded
      and the potential of the membrane itself are considered to cause differences in
      adsorption.

PMID- 14678430
TI  - Preservation of human saphenous vein against reactive oxygen species-induced
      oxidative stress by green tea polyphenol pretreatment.
AB  - The injurious effects of reactive oxygen species on venous tissues and the
      potential protective role played by green tea polyphenol (GTPP) on human
      saphenous veins were investigated. Oxidative stress was induced exogenously in
      the vein segments, either by adding 0.8 or 1.6 M of H2O2, or by using 80 or 160
      U/L of xanthine oxidase in the presence of xanthine (0.5 mM). After incubation,
      the viability of the endothelial cells dissociated from veins and the histology
      of the veins were evaluated. Due to both types of treatment, a significant
      decrease in cellular viability, severe morphological changes in the veins, and
      extracellular structural damage were induced. The H2O2-induced alterations were
      prevented by preincubating the veins with either 0.5 or 1.0 mg/ml of GTPP for 1
      h. When the oxidative stress was induced by xanthine oxidase, cellular viability
      and venous structure were preserved at the same polyphenol concentrations. These
      results demonstrate that GTPP can act as a biological antioxidant and protect
      veins from oxidative stress-induced toxicity.

PMID- 14678440
TI  - Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature.
AB  - Cutaneous paraneoplastic syndromes are a group of noncancerous dermatoses
      associated with internal malignancy. Their recognition can facilitate detection
      and timely treatment of underlying cancer. More than 30 such disorders have been
      identified in the human scientific literature, whereas only a few are described
      in veterinary medicine. This may reflect a lower incidence in animals than in
      people or may be the result of failure to recognize an association between
      certain skin lesions and neoplasia. Establishing a relationship between a
      cutaneous disorder and neoplasia can be difficult unless the skin lesions are
      rare and almost always associated with a particular tumour type, as is the case
      for most recognized veterinary paraneoplastic dermatoses. Among these are feline
      paraneoplastic alopecia, feline thymoma-associated exfoliative dermatitis,
      nodular dermatofibrosis, feminization syndrome associated with testicular
      tumours, superficial necrolytic dermatitis and paraneoplastic pemphigus. The
      aetiology of most cutaneous paraneoplastic syndromes has remained elusive in both
      people and animals.

PMID- 14678441
TI  - Ultrastructural study of cutaneous lesions in feline eosinophilic granuloma
      complex.
AB  - The purpose of this study was to investigate the ultrastructural appearance of
      flame figures, reported to comprise a mixture of degenerate collagen and
      degranulated eosinophils, in feline eosinophilic granuloma complex (EGC). Skin
      specimens from eight cats with EGC and from two clinically healthy cats were
      examined by transmission electron microscopy. Flame figures appeared to comprise
      ultrastructurally normal collagen fibrils separated by oedema and surrounded by
      large numbers of degranulating eosinophils. Longitudinal sections of collagen
      fibrils displayed the characteristic cross-striation of normal dermal collagen.
      Feline eosinophils, analogous to human eosinophils, degranulated both by
      cytolysis and piecemeal degranulation. The results of this study suggest that
      flame figures form in feline EGC due to eosinophil recruitment and degranulation,
      and that collagen fibres are partially disrupted but collagen fibrils are not
      damaged. These findings suggest that eosinophil accumulation and the release of
      granule contents represent the primary events in feline EGC.

PMID- 14678442
TI  - A recombinant 31.5 kDa keratinase and a crude exo-antigen from Microsporum canis
      fail to protect against a homologous experimental infection in guinea pigs.
AB  - A Microsporum canis recombinant 31.5 kDa keratinase and a M. canis crude exo
      antigen were tested as vaccines in an experimental infection model in guinea
      pigs. Animals were vaccinated subcutaneously three times at two-week intervals
      with either the keratinase, the exo-antigen or the adjuvant alone. Cutaneous
      challenge was performed blindly. Both humoral and cellular-specific immune
      responses to M. canis antigens were evaluated every 14 days, while a blind
      evaluation of clinical lesion development and fungal persistency in skin were
      monitored weekly. Vaccination induced very high and significant (P < 0.01)
      antibody responses towards both antigens. High cell-mediated immune responses to
      both immunogens were also induced by vaccination. After challenge, however,
      scores reflecting the severity of dermatophytic lesions did not differ
      significantly between vaccinated and control groups at any time after challenge.
      These results suggest that, in the guinea pig, the induction of specific immune
      responses against the M. canis-secreted antigens used in this study are not
      protective against challenge exposure.

PMID- 14678443
TI  - Feline pemphigus foliaceus: a retrospective analysis of 57 cases.
AB  - Fifty-seven cases of feline pemphigus foliaceus were identified from biopsy
      specimens submitted to University of Pennsylvania School of Veterinary Medicine's
      Laboratory of Pathology and Toxicology by veterinary dermatologists from 1991 to
      2002. Age at onset ranged from less than 1 year to 17 years; median 5 years.
      Eighty per cent of cats were reported to have been pruritic. At the time of
      biopsy, the distribution of lesions varied, but included some combination of
      face/head, paws, dorsum or ventrum and consisted of crusts, erosions, scale and
      alopecia. The histological features of 208 biopsy specimens were reviewed and
      included the following. Acantholytic cells were found in large numbers in both
      intact and degenerating pustules in most cases. Mast cells were found in the
      dermal infiltrate more often than reported previously. Seventeen cases were
      receiving corticosteroids at the time of biopsy; reducing the percentage of
      diagnostic biopsies per case. Forty-four cases were followed for 1-54 months
      (median 9 months). Triamcinolone was more successful at inducing remission
      without significant adverse effects than prednisone or prednisone in combination
      with chlorambucil. Only 4/44 cats died from their disease or therapy during the
      study period.

PMID- 14678444
TI  - Evaluation of intravenous fluorescein in intradermal allergy testing in
      psittacines.
AB  - This study was designed to improve the clinical feasibility of intradermal skin
      testing of psittacine birds using intravenous fluorescein stain. Twenty-five
      healthy, anaesthetized Hispaniolan Amazon parrots (Amazona ventralis) were
      injected intravenously with 10 mg kg-1 fluorescein-sodium 1% followed by
      intradermal injections of 0.02 mL phosphate-buffered saline, histamine phosphate
      (1:100,000 w/v) and codeine phosphate (1:100,000 w/v) at the sternal apteria.
      Wheal diameters of reaction sites were measured grossly and under illumination
      with a Wood's lamp after 5 and 10 min. Fluorescence-enhanced injection sites were
      scored between 0 and 2, with 0 equivalent to normal skin and 2 equivalent to a
      plucked feather follicle. The presence of a fluorescent halo around intradermal
      injections was also recorded. Under Wood's light illumination at 10 min,
      histamine and saline were evaluated as positive and negative controls,
      respectively, based on a positive test having a halo and a score of 2.
      Sensitivity and specificity were each 76% for halo, 84 and 42% for score and 64
      and 77% for combination of score and halo, respectively. Further, mean histamine
      reactions were significantly larger than codeine phosphate and saline (8.8 +/-
      0.4 mm; 7.2 +/- 0.3 mm; 5.9 +/- 0.6 mm); however, this finding was not consistent
      in individual birds. Wheal size, halo presence and score were affected by site
      location independent from the injected compound. Intravenous fluorescein improved
      the readability of avian skin tests; however, the compounds tested raised
      inconsistent reactions in wheal size, score or halo presence. The compound
      independent site effect raises concern on the validity of avian skin testing and
      warrants investigation of other techniques such as in vitro allergy testing.
      Based on our findings, intradermal allergy testing in psittacines with or without
      fluorescein is unreliable and cannot be recommended for practical clinical use.

PMID- 14678445
TI  - Feline plasma cell pododermatitis: a study of 8 cases.
AB  - Eight cases of feline plasma cell pododermatitis, collected over a 3-year period,
      were studied using histological (haematoxylin and eosin), histochemical (methyl
      green-pyronin) and immunohistochemical (antibody against lambda light chains of
      immunoglobulins) techniques. No sex, breed or age predisposition, or paw
      predilection was observed. The disease began as a swelling of the footpads,
      followed by ulceration. Histologically, lesions were characterized by the
      presence of a large number of plasma cells in a predominantly perivascular
      pattern. Binucleated plasma cells and mitotic figures were observed. Clinical
      follow-up for over 1 year revealed total remission of the lesions both after
      glucocorticoid therapy in four cases, and total surgical excision in two animals.
      Follow-up studies were not possible in one case.

PMID- 14678446
TI  - Notoedric mange in free-ranging masked palm civets (Paguma larvata) in Japan.
AB  - Fifty-one masked palm civets (Paguma larvata) were trapped as part of a nuisance
      wildlife control programme between July 2001 and August 2002 in Fujisawa City,
      Kanagawa Prefecture, Japan. Eleven civets had characteristic mange lesions with
      marked alopecia and crusts, caused by the burrowing epidermal mite Notoedres
      cati. The diagnosis was confirmed by histology and examination of mites obtained
      from skin scrapings of affected civets. Histopathology of lesions demonstrated
      moderate hyperplastic epidermis, parakeratosis and acanthosis. Occasionally
      microvascular angiogenesis was observed in the epidermis. Tunnels were excavated
      in the hair follicles, reaching the hair roots. The tunnels were located between
      the hair shaft and the inner root sheath. Female mites, eggs and nymphs were
      demonstrated in their tunnels using scanning electron microscopy.

PMID- 14678449
TI  - Development of a psychosomatic complaints scale for adolescents.
AB  - There have been only a few questionnaires that can be used to comprehend the
      psychosomatic complaints of adolescents. Therefore, the objective of the present
      investigation was to develop a scale for high school students in order to
      comprehend psychosomatic complaints deriving from psychologic problems. The
      collection of scale items was performed referring to the health actual situation
      survey carried out on Japanese school children in the past, and 30 items with a
      high incidence of psychosomatic complaints were selected out of them and were set
      as scale items. A survey to assess reliability and validity of the 30 items of
      the psychosomatic complaint scale was then conducted on the subjects of 759 high
      school students in total over 3 years. At assessment of validity of the scale,
      one-factor structure was confirmed by factor analysis and both the eigenvalue and
      factor loading were found to be at acceptable levels. Further, at assessment of
      the reliability of the scale, both Cronbach's alpha coefficient indicating
      internal consistency and the correlation coefficient indicating reproducibility
      were found to be high. It was concluded that the psychosomatic complaint scale
      developed in the present investigation was excellent in validity and reliability
      and was highly practical, having a reduced number of items.

PMID- 14678450
TI  - Socioeconomic and familial factors in the involuntary hospitalization of patients
      with schizophrenia.
AB  - In the catchment area of Matsumoto Public Health Center in Japan, 44
      schizophrenic patients admitted between April 1992 and March 1997 under the
      national policy Involuntary Hospitalization Ordered by Prefectural Governor
      (IHOPG) were compared with 61 schizophrenic patients admitted under another
      policy, Hospitalization for Medical Care and Protection (HMCP), during the same
      period. The socioeconomic and familial factors that led patients to IHOPG were
      evaluated in detail. The results revealed the following characteristics of IHOPG
      patients as opposed to HMCP patients: (i) their morbidity was of longer duration;
      (ii) they were more likely to live in a densely populated area; (iii) they were
      less likely to be financially self-sufficient; (iv) prior to admission they were
      more likely than HMCP patients to have avoided psychiatric examination and to
      have refused to take medication, and most had received no treatment before their
      hospitalization under IHOPG; (v) their relationships with family members were
      more likely to be poor; and (vi) the family was less likely to have cooperated
      with treatment or to have solved the patient's problematic behaviors. This
      investigation and the ensuing discussion revealed that a patient's schizophrenia
      based danger to hurt self or others, which is an essential impetus for admission
      to IHOPG, does not arise suddenly but rather stems from multiple factors
      developing over time.

PMID- 14678451
TI  - Association between EEG alpha power and visuospatial function in obsessive
      compulsive disorder.
AB  - The purpose of the present paper was to determine if frontal activity, measured
      as electroencephalogram alpha power, correlates with visuospatial functions in
      obsessive-compulsive disorder (OCD). Electroencephalography and the Rey
      Osterrieth Complex Figure Test (RCFT) were performed on 23 patients meeting the
      Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) OCD
      criteria. After quantitatively analyzing EEG recordings taken over the frontal,
      temporal, parietal and occipital regions (F1, F2, T3, T4, P3, P4, O1 and O2), the
      log transformed absolute power values of the alpha frequencies of the regions
      were regressed with each RCFT index (copy, immediate recall and delayed recall
      score). On the frontal region (F1, F2), the RCFT copy score was found to be
      correlated with the alpha power with regression coefficients that had different
      directions according to hemisphere (F1, 5.62; F2, -5.26). The result that visuo
      constructional ability represented by the RCFT copy score correlated with frontal
      activation as measured by decreased alpha power, supports the opinion that
      visuospatial dysfunction in OCD is not in the visuospatial memory per se but
      rather that it is mediated by executive function deficit. The opposite
      correlation directions indicate that greater left frontal activation correlates
      with a poorer RCFT copy score and that greater right frontal activation
      correlates with a better copy score. These relationships provide indirect
      evidence of the possibility that the main pathology of OCD is located in the left
      hyperfrontality and that the right hyperfrontality of OCD occurs by a
      compensatory mechanism.

PMID- 14678452
TI  - No evidence for an association of the CTLA4 gene with bipolar I disorder.
AB  - The purpose of the present paper was to investigate the relationship between the
      first exon at position +49 (A/G) polymorphism of the cytotoxic T lymphocyte
      antigen 4 (CTLA4) gene and bipolar disorder. Among the Korean patients diagnosed
      with bipolar disorder according to Diagnostic and Statistical Manual of Mental
      Disorders (4th edn; DSM-IV), 90 patients without serious medical illness,
      neurologic illness, hormonal disorder, or concomitant mental illness were
      selected. The normal control group consisted of 149 age- and sex-matched subjects
      without current or past history of autoimmune diseases or mental disorder. DNA
      was extracted from peripheral blood using proteinase K; and the exon 1 region of
      the CTLA4 gene was amplified by polymerase chain reaction. Gene typing was
      performed using single strand conformation polymorphism. There were no
      significant differences in genotype frequencies of CTLA4*G/G, CTLA4*G/A, and
      CTLA4*A/A between the patients with bipolar disorder and the control group (48.9%
      vs 46.3%, 44.4% vs 39.6%, and 6.7% vs 14.1%, respectively). There were no
      significant differences in allelic frequencies of CTLA4*G and CTLA4*A between the
      patients with bipolar disorder and the control group (71.1% vs 66.1%; 28.9% vs
      33.9%, respectively). In the present study an association was not found of exon 1
      (+49) polymorphism of CTLA4 gene with bipolar disorder in the Korean population.

PMID- 14678453
TI  - Implication of serum concentration monitoring in patients with lithium
      intoxication.
AB  - The aim of the present study was to determine the relationships between serum
      lithium level, duration of lithium intoxication, severity of symptoms, and the
      outcome of the disease. Subjects with a serum lithium level of >/=1.2 mEq/L were
      included in the study. Seventy-eight patients with lithium intoxication were
      identified between 1 July 1999 and 31 December 2002. The demographic
      characteristics, clinical manifestations, and concomitant medications were
      recorded. Most patients with acute lithium intoxication had mild symptoms,
      independent of the serum lithium levels. In patients with chronic lithium
      intoxication, the frequency of severe symptoms was higher than in those with
      acute intoxication. None of the 78 intoxicated patients in the present survey
      died or suffered from persistent neurological sequelae. Patients with concomitant
      medications, older age, and existing neurological illness may have an increased
      susceptibility to lithium toxicity. Regular monitoring of serum lithium level is
      essential for lithium-treated patients. Clinicians should pay attention to
      patients with pre-existing neurological illness, older age, or receiving
      medications that may interact with lithium.

PMID- 14678454
TI  - Effect of the combination of naltrexone and acamprosate on alcohol intake in
      mice.
AB  - Both naltrexone and acamprosate have been utilized clinically in recovering
      alcoholics with varying success. In the experiment reported here the combination
      of naltrexone and acamprosate was examined in a limited access alcohol model
      using C57BL/6 mice to determine if there was evidence of additive or synergistic
      effects. The results of this experiment demonstrate that naltrexone, at the
      higher dose but not the lower dose, significantly reduced alcohol consumption.
      When combined with naltrexone, acamprosate reduced alcohol consumption across
      both doses of naltrexone. This effect was sensitive to both dose and number of
      days of exposure to the naltrexone/acamprosate combination.

PMID- 14678455
TI  - Rapid improvement in academic grades following methylphenidate treatment in
      attention-deficit hyperactivity disorder.
AB  - In the present study a 16 week comparison study was conducted of behavioral,
      cognitive and educational measures in school-age Taiwanese children with
      attention-deficit hyperactivity disorder (ADHD) receiving open-label
      methylphenidate (MPH). Subjects include 14 male and five female ADHD children.
      They received MPH twice per day continuously for 16 weeks. Measures of behavior,
      cognitive function (Wisconsin Card Sorting Test, Tower of London and Continuous
      Performance Test), Chinese and arithmetic learning achievement were compared with
      those of their baseline condition. After MPH, 68-78% of children showed improving
      behavior in classroom and at home. Among the neuropsychological tests, only the
      percentage of preservative error was improved (P = 0.022). Approximately 61-66%
      of children had improvement in academic learning (P = 0.013 for Chinese, 0.004
      for arithmetic). The MPH treatment demonstrated improvement in domains of
      classroom/home behaviors and academic performance, but showed minimal change on
      neuropsychological functioning in Taiwanese ADHD children. The finding of
      academic gain was unexpected, which might be due to the greater interest in
      achievement and better compliance to cultural expectations by Taiwanese versus
      Western students, which translated into more rapid improvement in academic
      performance.

PMID- 14678456
TI  - Three-year follow up of women with and without borderline personality disorder:
      development of Cloninger's character in adolescence.
AB  - The purpose of the present study was to examine the developmental patterns of
      Cloninger's biogenetic character traits in subjects with borderline personality
      disorder (BPD). Study subjects met Diagnostic and Statistical Manual of Mental
      Disorders (3rd edn, revised; DSM-III-R) criteria for BPD without comorbid axis I
      or II disorders, as determined by the Diagnostic Interview for Borderlines
      Revised, Structured Clinical Interview for the DSM-III-R, and Diagnostic
      Interview for Personality Disorders. The BPD subjects and age- and sex-matched
      healthy comparison subjects were initially interviewed for Cloninger's biogenetic
      characters and re-interviewed at an interval of 1 year for the following 3 years.
      There were significant differences in the developmental patterns of self
      directedness, cooperativeness, and self-transcendence between BPD and healthy
      comparison subjects (significant group by time interaction: repeated measures
      manova, F = 17.3, d.f. = 3,240, P < 0.001; F = 28.5, d.f. = 3,240, P < 0.001; F =
      4.7, d.f. = 3,240, P < 0.01, respectively). The BPD subjects had less changes in
      character-related maturity with increasing age than did healthy comparison
      subjects. Post-hoc tests with Duncan's statistics revealed that subjects with BPD
      had significantly lower scores on self-directedness at all assessment time
      periods (P < 0.01) and lower scores on cooperativeness at the second-year and
      third-year follow-up assessments as compared to healthy comparison subjects (P <
      0.01). The BPD subjects had a distinctively different developmental pattern of
      Cloninger's character compared to healthy comparison subjects. The character
      development of BPD patients was more fixed and immature than those of healthy
      comparison subjects.

PMID- 14678457
TI  - Neural damage due to temporal lobe epilepsy: dual-nuclei (proton and phosphorus)
      magnetic resonance spectroscopy study.
AB  - The aim of this study was to evaluate the usefulness of proton and phosphorus (1H
      and 31P) magnetic resonance spectroscopy (MRS) for temporal lobe epilepsy (TLE)
      patients, and to evaluate neural damage and metabolite dysfunction in the TLE
      patient brain. We performed 1H and 31P MRS of medial temporal lobes (MTL) in the
      same TLE patients (n = 14) with a relatively wide range of severity from almost
      seizure-free to intractable, and calculated the ratio of N-acetylasparate to
      choline-containing compounds and creatine + phosphocreatine (NAA/Cho + Cr) in 1H
      MRS and inorganic phosphate to all main peaks (%Pi) in 31P MRS. There was no
      significant correlation between NAA/(Cho + Cr) and %Pi in each side (ipsilateral,
      r = -0.20; contralateral, r =-0.19). The values of NAA/(Cho + Cr) showed a
      significant difference between ipsilateral and contralateral MTLs to the focus of
      TLE patients (P < 0.01, paired t-test). Although %Pi also had a tendency to show
      the laterality of TLE, there was no significance. Ipsilateral (r = -0.90, P <
      0.0001) and contralateral (r = -0.70, P < 0.005) NAA/(Cho + Cr) decreases and
      contralateral %Pi increase (r = 0.81, P < 0.001) had significant correlation with
      seizure frequency. 1H MRS provides more important information concerning neuronal
      dysfunction in MTL of TLE patients than 31P MRS.

PMID- 14678458
TI  - Executive dysfunction can explain word-list learning disability in very mild
      Alzheimer's disease: the Tajiri project.
AB  - Elderly people with questionable dementia (i.e. a Clinical Dementia Rating (CDR)
      of 0.5) have been focused on as representing the borderline zone condition
      between healthy people and dementia patients. Many of them are known to have
      pathologic traits of very mild Alzheimer's disease (AD). Although they present
      mild memory disorder, the underlying mechanism has not been fully investigated.
      Herein is reported the mechanism of learning disability in very mild AD. Eighty
      six CDR 0.5 participants and 101 age- and education-matched healthy controls (CDR
      0) were randomly selected from a community in the town of Tajiri, Miyagi
      Prefecture. The word-recall task of the Alzheimer Disease Assessment Scale
      Japanese (i.e. learning and recall of 10 words) was administered. The numbers of
      words recalled in each trial and those never recalled throughout the trials were
      compared for the two CDR groups. The serial-position function was depicted for
      three parts (i.e. primary, middle, and recency). The CDR 0.5 group recalled
      significantly fewer words than the CDR 0 group. The number of never-recalled
      words was greater in the CDR 0.5 group. A remarkable difference was found in the
      middle part of the word list. The number of never-recalled words of the CDR 0.5
      group was greater in the middle part. The large number of never-recalled words
      accounted for the poor learning performance of very mild AD participants. The
      results suggested that very mild AD participants have difficulty in learning and
      retaining words in the middle part of the word-list because of a functional
      decline of the central executive system.

PMID- 14678459
TI  - Antipsychotic drug prescription for schizophrenia in East Asia: rationale for
      change.
AB  - The purpose of this international collaborative study was to investigate the
      prescription patterns of antipsychotic drugs for schizophrenia in East Asia and
      to analyze factors that affect these patterns. Prescription patterns for patients
      admitted for treatment of schizophrenia were surveyed using a standardized
      protocol from six East-Asian region/countries: China, Hong Kong, Japan, Korea,
      Singapore and Taiwan. Patients' social and clinical characteristics, psychiatric
      symptoms, course of illness, and adverse effects of medications were
      systematically assessed and recorded. Prescriptions of the first- and second
      generation antipsychotic drugs were compared. A total of 2399 patients were
      recruited. The second-generation drugs comprised 28.1% of all prescribed
      antipsychotics, and 46% of the antipsychotic prescriptions were in the context of
      polypharmacy. The mean dosage of antipsychotics for the whole sample was 675.3 +
      645.1 mg chlorpromazine equivalents. Japan had a high frequency of prescribing
      high doses and polypharmacy; Singapore had a high utilization of depot injections
      while China had a higher prescription of clozapine. Using multiple logistic
      regression analysis, distinctions in the prescription patterns of antipsychotic
      drugs were found: first-generation drugs were mainly for controlling aggressive
      behavior, while second-generation drugs were targeted at the alleviation of
      positive, negative psychotic symptoms as well as disruptive behavior in
      schizophrenia. The present collaborative study highlighted differences in the
      prescription patterns, especially the under-utilization of second-generation
      antipsychotic drugs in East Asia. The pattern of antipsychotic medication use
      varied from country to country and is likely to be influenced by the prevailing
      health-care system, the availability and cost of the drugs.

PMID- 14678460
TI  - Abnormalities of P300 cortical current density in unmedicated depressed patients
      revealed by LORETA analysis of event-related potentials.
AB  - The purpose of the present study was to investigate the neural substrates
      underlying event-related potential (ERP) abnormalities, with respect to the
      generators of the ERP components in depressed patients. Using an oddball
      paradigm, ERP from auditory stimuli were recorded from 22 unmedicated patients
      with current depressive episodes and compared with those from 22 age- and gender
      matched normal controls. Cortical current densities of the N100 and P300
      components were analyzed using low-resolution electromagnetic tomography
      (LORETA). Group differences in cortical current density were mapped on a 3-D
      cortex model. The results revealed that N100 cortical current densities did not
      differ between the two groups, while P300 cortical current densities were
      significantly lower in depressed patients over the bilateral temporal lobes, the
      left frontal region, and the right temporal-parietal area. Furthermore, the
      cortical area in which the group difference in P300 current density had been
      identified was remarkably larger over the right than the left hemisphere, thus
      supporting the hypothesis of right hemisphere dysfunction in depression.

PMID- 14678461
TI  - Duration of untreated psychosis and pathways to psychiatric services in first
      episode schizophrenia.
AB  - The aim of the present study was to examine the duration of untreated psychosis
      (DUP) in first-episode schizophrenia patients in Japan and to investigate the
      available pathways to psychiatric services. Eighty-three patients who visited
      Keio University Hospital (n = 54) or Oizumi Mental Hospital (n = 29) were
      evaluated retrospectively with regard to their DUP, living situation, social
      participation level, referral pathway, reason for seeking treatment, and their
      global assessment of functioning (GAF) score. The mean DUP was 13.7 months
      (median, 5.0 months) overall. No significant difference in DUP was found between
      subjects living alone and those living with others; however, employed patients
      had a significantly shorter DUP (8.1 months) than unemployed patients (18.7
      months). Pathways to psychiatric services were totally different between the two
      institutions. Fifty-two subjects (62.7%) came to the services directly: 40
      patients (74.1%) came to the university hospital and 12 patients (41.4%) came to
      the mental hospital. At the mental hospital, nine patients (31.0%) had been
      admitted because of a legal obligation, and six (20.7%) had been referred through
      public health centers. None of the patients had been referred to either of the
      services by general practitioners. The main reason for seeking treatment was
      psychiatric symptom aggravation (59.3%) at the university hospital and acting out
      (64.3%) at the mental hospital. Some universal psychosocial factors appear to
      influence the DUP but the characteristics of specific psychiatric services may
      also affect treatment delays.

PMID- 14678462
TI  - Reduced intracellular pH in the basal ganglia and whole brain measured by 31P-MRS
      in bipolar disorder.
AB  - The authors have previously reported that intracellular pH measured by phosphorus
      31 magnetic resonance spectroscopy (31P-MRS) was decreased in the frontal lobes
      of patients with bipolar disorder. In the present study, phosphorus metabolism in
      the basal ganglia was examined in 13 patients with bipolar disorder and 10
      matched controls by localized 31P-MRS. While no significant alteration of peak
      area ratios was found for all phosphorus metabolites, intracellular pH was
      significantly reduced in the basal ganglia in patients with bipolar disorder
      (7.014 +/- 0.045) compared with control subjects (7.066 +/- 0.047, P < 0.05).
      Unexpectedly, non-localized 31P-MR spectra also showed significantly lower levels
      of intracellular pH (6.970 +/- 0.025) than controls (6.986 +/- 0.024, P < 0.05).
      These results suggest that decreased intracellular pH in the brain of patients
      with bipolar disorder is not caused by dysfunction of the frontal lobes but
      reflect altered metabolism at the cellular level.

PMID- 14678463
TI  - Attitudes of psychiatrists toward patients with schizophrenia.
AB  - A questionnaire was distributed to psychiatrists to investigate their attitudes
      toward patients with schizophrenia. A total of 42.7% of 60 respondents never
      informed patients of the diagnosis of schizophrenia and 40.7% informed on a case
      by-case basis. The reason that psychiatrists gave for avoiding informing the
      patients/family members of the diagnosis was the idea that they would not
      understand the meaning (32.6%) and that they would drop-out from treatment
      (28.3%). A total of 88.4% of respondents thought the term 'schizophrenia' was
      used in a pejorative manner in public. The findings revealed that stigmatizing
      attitudes of society are also shared by some psychiatrists.

PMID- 14678464
TI  - Venlafaxine in children and adolescents with attention deficit hyperactivity
      disorder.
AB  - The primary purpose of this study was to describe tolerability and efficacy of
      venlafaxine in the treatment of children and adolescents with attention deficit
      hyperactivity disorder (ADHD). A 6-week open trial of venlafaxine was conducted
      in 13 children and adolescents (mean age 9.9 +/- 2.5 years) with ADHD, and
      without comorbid depression. Venlafaxine was initiated at a dose of 18.75 mg/day
      and flexibly titrated to 56.25 mg/day. The Conners parent scale and Clinical
      Global Improvement (CGI) severity item were performed at baseline and at the end
      of the 6-week trial. All subjects completed the trial. Mean final dose of
      venlafaxine was 40.3 +/- 7.0. Venlafaxine was significantly effective in reducing
      the total score of the Conners parent scale from baseline to endpoint (P < 0.002,
      Z =-3.113) and the CGI severity item (P < 0.05). Transient side-effects such as
      somnolence (n = 2), stomachache (n = 2), and headache (n = 1) disappeared after
      second week of treatment. Also three subjects complained of sedation after
      raising the dose to 56.5 mg/day, therefore the dose was reduced to the previous
      level. These preliminary data suggest that venlafaxine may be an effective
      medication in the treatment of some children and adolescents with ADHD. Future
      double-blind controlled trials should be undertaken.

PMID- 14678465
TI  - Musical and auditory hallucinations: A spectrum.
AB  - Musical hallucinosis is a rare and poorly understood clinical phenomenon. While
      an association appears to exist between this phenomenon and organic brain
      pathology, aging and sensory impairment the precise association remains unclear.
      The authors present two cases of musical hallucinosis, both in elderly patients
      with mild-moderate cognitive impairment and mild-moderate hearing loss, who
      subsequently developed auditory hallucinations and in one case command
      hallucinations. The literature in reference to musical hallucinosis will be
      reviewed and a theory relating to the development of musical hallucinations will
      be proposed.

PMID- 14678466
TI  - The assessment of cognitive function in a Williams syndrome patient: a case
      report.

PMID- 14678467
TI  - A follow-up study of graduates from special classes for school refusers in junior
      high schools.

PMID- 14678468
TI  - Identification of T-cell epitopes of Porphyromonas gingivalis heat-shock-protein
      60 in periodontitis.
AB  - The heat shock proteins (hsp) of bacterial species are considered to be involved
      in regulating the autoimmune mechanism in human diseases due to the considerable
      homology of their sequences with human hsp. To elucidate how stress proteins
      contribute to the immunopathogenesis of periodontitis, mononuclear cells from
      gingival connective tissue of 10 periodontitis patients were simulated with
      Porphyromonas gingivalis hsp60. T-cell lines reactive to P. gingivalis hsp60 were
      established from each patient to define T-cell epitope specificities. Anti-P.
      gingivalis IgG antibody titres were elevated in all patients. We could establish
      P. gingivalis hsp-reactive T-cell lines from gingival mononuclear cells that were
      mixtures of CD4+ and CD8+ cells. Of 108 overlapping synthetic peptides spanning
      the whole P. gingivalis hsp60 molecule, 10 peptides with epitope specificities
      for T-cells were identified, and were identical to those reported be B-cell
      epitopes in periodontitis.

PMID- 14678469
TI  - Characterization of two outer membrane protein antigens of Porphyromonas
      gingivalis that are protective in a murine lesion model.
AB  - Porphyromonas gingivalis is a key periodontal pathogen that has been implicated
      in the aetiology of chronic adult periodontitis. The aim of this study was to
      characterize two potential vaccine candidates (PG32 and PG33) identified from a
      previous genomic sequence analysis. Gene knockout studies suggested that these
      proteins play an important role in bacterial growth and are transcriptionally
      linked. Analysis of 14 laboratory and clinical isolates of P. gingivalis found
      that in all strains, both genes were present with a high level of conservation
      and that the two proteins were also expressed in vitro. Truncated recombinant
      PG32 and PG33 proteins were produced in Escherichia coli in an attempt to
      increase the solubility of the proteins while retaining their native
      conformation. While most of the truncated proteins remained insoluble, two
      truncated proteins showed good solubility and high levels of protection in the P.
      gingivalis murine lesion model and may be considered as potential vaccine
      candidates for further testing in models of human periodontal disease.

PMID- 14678470
TI  - Two epithelial cell invasion-related loci of the oral pathogen Actinobacillus
      actinomycetemcomitans.
AB  - Two invasion-related loci, apiA and the two-gene operon apiBC, were isolated from
      the oral pathogen Actinobacillus actinomycetemcomitans UT32. apiA encodes a 32.5
      kDa protein that migrates on SDS-PAGE as a 101 kDa protein as detected by Western
      blot analysis or silver staining of an outer membrane-enriched fraction of
      Escherichia coli transformants. E. coli expressing ApiA have a different
      phenotype than the host vector, in broth and on solid media, and a colony
      morphology that resembles that of fresh A. actinomycetemcomitans isolates. These
      E. coli transformants bound to chicken collagen type II, human collagen type II,
      III, V and fibronectin. apiB and apiC encode proteins of 130.1 and 70.6 kDa,
      respectively. ApiBC conferred on E. coli a slightly enhanced ability to bind to
      collagen type III. ApiA- and ApiB-deficient mutants were constructed in A.
      actinomycetemcomitans. The ApiB-mutant had 4-fold diminished invasion of KB
      cells; the ApiA-mutant had increased invasion. Both loci were found in all A.
      actinomycetemcomitans strains, although polymorphism was detected only for apiBC.
      The deduced sequences of these invasion-related proteins are homologous to
      members of the YadA adhesin/invasin family.

PMID- 14678471
TI  - Platelet responses and anaphylaxis-like shock induced in mice by intravenous
      injection of whole cells of oral streptococci.
AB  - Intravenous injection of lyophilized whole cells of various oral streptococcal
      strains into muramyldipeptide (MDP)-primed C3H/HeN mice induces rapid
      anaphylactoid shock. Here we examined the mechanism underlying this shock. In non
      primed mice, Streptococcus intermedius K-213K (SiK213) and Streptococcus
      constellatus T21 (ScT21) produced little or no sign of shock. In MDP-primed mice,
      SiK213 caused lethal shock, while ScT21 only had a weak effect. SiK213 induced
      decreases in blood platelets and 5-hydroxytryptamine (5HT) preceding the shock,
      while the effects of ScT21 were weak. The SiK213-induced 5HT decrease and shock
      were reduced by a complement-C5 inhibitor. These results suggest that (i).
      streptococcal bacterial cells can induce rapid platelet responses, (ii).
      complement-dependent degradation of platelets may be involved in streptococcus
      induced shock, (iii). the streptococcus-induced platelet degradation or
      degranulation may occur largely in the systemic circulation, and (iv). platelets
      may play a role not only in infectious diseases caused by gram-negative bacteria,
      but also in diseases caused by gram-positive bacteria.

PMID- 14678472
TI  - Physiologic actions of zinc related to inhibition of acid and alkali production
      by oral streptococci in suspensions and biofilms.
AB  - Zinc is a known inhibitor of acid production by mutans streptococci. Our primary
      objective was to extend current knowledge of the physiologic bases for this
      inhibition and also for zinc inhibition of alkali production by Streptococcus
      rattus FA-1 and Streptococcus salivarius ATCC 13419. Zinc at concentrations as
      low as 0.01-0.1 mm not only inhibited acid production by cells of Streptococcus
      mutans GS-5 in suspensions or in biofilms but also sensitized glycolysis by
      intact cells to acidification. Zinc reversibly inhibited the F-ATPase of
      permeabilized cells of S. mutans with a 50% inhibitory concentration of about 1
      mm for cells in suspensions. Zinc reversibly inhibited the phosphoenolpyruvate:
      sugar phosphotransferase system with 50% inhibition at about 0.3 mm ZnSO4, or
      about half that concentration when the zinc-citrate chelate was used. The
      reversibility of these inhibitory actions of zinc correlates with findings that
      it is mainly bacteriostatic rather than bactericidal. Zinc inhibited alkali
      production from arginine or urea and was a potent enzyme inhibitor for arginine
      deiminase of S. rattus FA-1 and for urease of S. salivarius. In addition, zinc
      citrate at high levels of 10-20 mm was weakly bactericidal.

PMID- 14678473
TI  - Alteration of gene expression profiles of peripheral mononuclear blood cells by
      tobacco smoke: implications for periodontal diseases.
AB  - Alterations of the host response by tobacco smoke adversely affect the
      periodontium. In this study, we examined the effects of in vitro acute smoke
      exposure on changes in m-RNA expression of primary peripheral mononuclear blood
      cells through microarray analysis. Mononuclear blood cells were isolated from
      four healthy non-smokers and plated in culture wells. Half of the cells were then
      exposed to 5 min of tobacco smoke. Fluorescent c-DNA probes were prepared from
      the linearly amplified m-RNAs for each sample and hybridized to cDNA microarrays
      representing approximately 30000 human genes. Significant increases or decreases
      in m-RNA gene expression between non-smoke-exposed and smoke-exposed samples were
      identified by permutation t-test, as implemented by the Significance Analysis of
      Microarrays software package. After smoke exposure, the expression of 90 genes
      with known function was significantly elevated and the expression of 19 genes
      with known function was significantly depressed. In addition, 18 upregulated and
      26 downregulated transcripts were expressed sequence tags with little information
      available on function. Approximately 20 of the significantly elevated genes had
      previously been reported in the literature to be associated with periodontal
      pathogenesis (fold changes in parentheses). These included plasminogen activator
      (4.4), Heat Shock Protein (Hsp) 40 kD (2.2), thrombomodulin (4.2), cytochrome c
      (1.8), COX-2 (2.6), interleukin-1a (1.4), chemokine ligand 1 (3.8), cathepsin L
      (2.0), and calgranulin A (2.1). In addition, several significantly elevated genes
      not previously reported in the literature may also play a role in periodontal
      pathogenesis, and thus warrant further investigation. These include Diphtheria
      toxin receptor (heparin-binding epidermal growth factor-like growth factor)
      (7.8), Hsp 10 kDa (1.7), Hsp 105 kD (2.1), Hsp 70 kDa (1.6), and mitogen
      activated protein kinase 3 (1.5). Among the significantly depressed genes that
      may play a protective or destructive role in periodontal pathogenesis were
      interferon gamma receptor 2 (0.58) and chemokine receptor 2 (0.24). Our results
      may be of use in the search for the molecular mechanisms for the adverse effects
      of tobacco smoke on the host response.

PMID- 14678474
TI  - Hemoglobin hydrolysis and heme acquisition by Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis has been implicated in the progression of chronic
      periodontitis, an inflammatory disease of the supporting tissues of the teeth.
      This bacterium is a gram-negative, black-pigmented, asaccharolytic anaerobe that
      relies on the fermentation of amino acids for the production of metabolic energy.
      The Arg- and Lys-specific extracellular cysteine proteinases of P. gingivalis,
      RgpA, RgpB and Kgp have been implicated as major virulence factors. In this study
      we investigated the hydrolysis of human hemoglobin by whole cells of P.
      gingivalis W50 and the mutants W501 (RgpA-), W50AB (RgpA-RgpB-) and W50ABK (RgpA
      RgpB-Kgp-) under strictly anaerobic conditions in a physiological buffer (pH 7.5)
      using mass spectrometric analysis. Incubation of P. gingivalis W50 with
      hemoglobin over a period of 30 min resulted in the detection of 20 hemoglobin
      peptides, all with C-terminal Arg or Lys residues. The majority of the hemoglobin
      alpha- and beta-chain sequences were recovered as peptides except for two similar
      regions of the C-terminal half of each chain, alpha(92-127) and beta(83-120). The
      residues of the unrecovered sequences form part of the interface between the
      alpha- and beta-chains and an exposed surface area of the hemoglobin tetramer
      that may be involved in binding to P. gingivalis. P. gingivalis W501 (RgpA-)
      produced similar peptides to those seen in the wild-type. All identified peptides
      from the hydrolysis of hemoglobin by the P. gingivalis W50AB (RgpA-RgpB-) mutant
      were the result of cleavage at Lys. The triple mutant W50ABK was unable to
      hydrolyze hemoglobin under the assay conditions used, suggesting that on whole
      cells the major cell surface activity responsible for hydrolysis of hemoglobin is
      from the RgpA/B and Kgp proteinases. However, the triple proteinase mutant W50ABK
      grew as well as the wild-type in a medium containing hemoglobin as the only iron
      source, indicating that the RgpA/B and Kgp proteinases are not essential for iron
      assimilation from hemoglobin by P. gingivalis.

PMID- 14678475
TI  - Inactivation of srtA gene of Streptococcus mutans inhibits dextran-dependent
      aggregation by glucan-binding protein C.
AB  - A sortase-deficient mutant of Streptococcus mutans was prepared by insertional
      inactivation of a sortase gene (srtA). The srtA mutant was defective in cell wall
      anchoring of two surface proteins 200 and 75 kDa in size. A previous study has
      shown that the 200 kDa protein is a surface protein antigen PAc and that the
      sortase catalyzes cell wall-anchoring of PAc in S. mutans. In this study another
      surface protein 75 kDa in size was examined by immunologic and physiologic
      methods. Western blot analysis with a specific antiserum showed that the 75 kDa
      protein was a surface protein, glucan-binding protein C. The protein was
      overexpressed under a stress condition including a sublethal concentration of
      tetracycline. The srtA mutant cells also lost the ability of dextran-dependent
      aggregation. These results suggest that the S. mutans sortase mediates cell wall
      anchoring of the glucan-binding protein C and dextran-dependent aggregation of
      this organism.

PMID- 14678476
TI  - A comparison of the antibacterial efficacies of essential oils against oral
      pathogens.
AB  - Cariogenic bacteria and periodontopathic bacteria are present in dental plaque as
      biofilms. In this study, we investigated the antibacterial effects of essential
      oils on the following oral bacteria: Porphyromonas gingivalis, Actinobacillus
      actinomycetemcomitans, Fusobacterium nucleatum, Streptococcus mutans, and
      Streptococcus sobrinus. We tested manuka oil, tea tree oil, eucalyptus oil,
      lavandula oil, and romarinus oil and determined their minimum inhibitory
      concentration and minimum bactericidal concentration. The essential oils
      inhibited the growth of the bacteria tested, manuka oil being the most effective.
      Minimum bactericidal concentration values showed that lavandula oil acts
      bacteriostatically, and the remaining oils, bactericidally. Periodontopathic
      bacterial strains tested were killed completely by exposure for 30 s to 0.2%
      manuka oil, tea tree oil or eucalyptus oil. Tea tree oil and manuka oil showed
      significant adhesion-inhibiting activity against P. gingivalis. All the essential
      oils tested inhibited the adhesion of S. mutans. This study showed that, among
      the essential oils tested, manuka oil and tea tree oil in particular had strong
      antibacterial activity against periodontopathic and cariogenic bacteria. From the
      viewpoint of safety, we also examined the effects of these essential oils on
      cultured human umbilical vein endothelial cells and found that, at a
      concentration of 0.2%, they had little effect on cultured cells.

PMID- 14678478
TI  - The impact of Blue Cross conversions on accessibility, affordability, and the
      public interest.

PMID- 14678479
TI  - The effect of hospital ownership conversions on nonacute care providers.

PMID- 14678480
TI  - The rise and fall of a Kaiser Permanente expansion region.

PMID- 14678481
TI  - "Evil habits" and "personal choices": assigning responsibility for health in the
      20th century.

PMID- 14678483
TI  - The scents of androstenone in humans.

PMID- 14678484
TI  - Physiological genomics: tools and concepts.

PMID- 14678485
TI  - Nuclear transfer in rodents.
AB  - Cloning is the asexual reproduction of an individual, such that the offspring
      have an essentially identical nuclear genome. Nuclear transfer and cloning have
      been achieved in a number of species, namely sheep, cows, goats, rabbits, cats
      and mice, but have been largely unsuccessful, so far, in dogs, primates and rats.
      Clearly, contributory factors which affect the outcome of successful cloning
      experiments are not universally applicable to all species. One theme common to
      all cloning experiments, however, is the overall inefficiency of the process,
      typically 0-4%. A number of factors contribute to nuclear transfer inefficiency,
      and we will review mouse cloning experiments, which address these problems,
      highlighting the importance of donor nucleus choice (somatic or ES cell, fetal or
      adult, quiescent or actively dividing). Finally, we will summarize the emerging
      principles which appear to govern nuclear reprogramming and production of clones,
      and will consider the application of nuclear transfer to the rat.

PMID- 14678486
TI  - Moving forward with chemical mutagenesis in the mouse.
AB  - The study of genetic variation in mice offers a powerful experimental platform
      for understanding gene function. Complex trait analysis, gene-targeting and gene
      trapping technologies, as well as insertional and chemical mutagenesis approaches
      are becoming increasingly sophisticated and provide a variety of options for
      cataloguing gene activities and interactions. In this review we discuss
      fundamental and practical concepts related to chemical mutagenesis and we
      highlight the growing list of strategies for performing mutagenesis screens in
      mice. Gene-driven and diverse types of phenotype-driven screens provide several
      options for the recovery of the invaluable variety of alleles generated by
      chemical mutagenesis. The unique advantages offered using chemical mutagenesis
      compare favourably to and complement the spectrum of approaches available for
      functional annotation of the mammalian genome.

PMID- 14678487
TI  - High throughput gene expression profiling: a molecular approach to integrative
      physiology.
AB  - Integrative physiology emphasizes the importance of understanding multiple
      pathways with overlapping, complementary, or opposing effects and their
      interactions in the context of intact organisms. The DNA microarray technology,
      the most commonly used method for high-throughput gene expression profiling, has
      been touted as an integrative tool that provides insights into regulatory
      pathways. However, the physiology community has been slow in acceptance of these
      techniques because of early failure in generating useful data and the lack of a
      cohesive theoretical framework in which experiments can be analysed. With recent
      advances in both technology and analysis, we propose a concept of
      multidimensional integration of physiology that incorporates data generated by
      DNA microarray and other functional, genomic, and proteomic approaches to achieve
      a truly integrative understanding of physiology. Analysis of several studies
      performed in simpler organisms or in mammalian model animals supports the
      feasibility of such multidimensional integration and demonstrates the power of
      DNA microarray as an indispensable molecular tool for such integration.
      Evaluation of DNA microarray techniques indicates that these techniques, despite
      limitations, have advanced to a point where the question-driven profiling
      research has become a feasible complement to the conventional, hypothesis-driven
      research. With a keen sense of homeostasis, global regulation, and quantitative
      analysis, integrative physiologists are uniquely positioned to apply these
      techniques to enhance the understanding of complex physiological functions.

PMID- 14678488
TI  - Comparative genomic analysis as a tool for biological discovery.
AB  - The recent completion of the human genome sequence has enabled the identification
      of a large fraction of our gene catalogue and their physical chromosomal
      position. However, current efforts lag at defining the cis-regulatory sequences
      that control the spatial and temporal patterns of each gene's expression. This
      task remains difficult due to our lack of knowledge of the vocabulary controlling
      gene regulation and the vast genomic search space, with greater than 95% of our
      genome being noncoding. Recent comparative genomic-based strategies are beginning
      to aid in the identification of functional sequences based on their high levels
      of evolutionary conservation. This has proven successful for comparisons between
      closely related species such as human-primate or human-mouse, but also holds true
      for distant evolutionary comparisons, such as human-fish or human-bird. In this
      review we provide support for the utility of cross-species sequence comparisons
      by illustrating several applications of this strategy, including the
      identification of new genes and functional non-coding sequences. We also discuss
      emerging concepts as this field matures, such as how to properly select which
      species for comparison, which may differ significantly between independent
      studies.

PMID- 14678489
TI  - Identifying genes and genetic variation underlying human diseases and complex
      phenotypes via recombination mapping.
AB  - Understanding the mechanisms by which DNA and DNA variation influence diseases,
      naturally occurring phenotypic variation, and complex biological systems, has
      been one of the major tasks associated with contemporary human genetics research.
      The identification and characterization of specific genetic variations that
      influence particular human diseases and phenotypes is complicated by the fact
      that most diseases and phenotypes are influenced by many genetic and
      environmental factors. Thus, the identification of any particular phenotypically
      relevant factor might be hampered as other relevant factors may obscure its
      individual effect. Over the years numerous methods and study designs have been
      described to identify disease causing genes and mutations. One in particular -
      meiotic or recombination mapping - has received considerable attention over the
      last 50 years, and has been used widely with varying degrees of success. This
      review describes the motivation behind, and problems associated with,
      recombination mapping, in terms of both linkage mapping and linkage
      disequilibrium mapping.

PMID- 14678490
TI  - Application of chromosomal substitution techniques in gene-function discovery.
AB  - A consomic rat strain is one in which an entire chromosome is introgressed into
      the isogenic background of another inbred strain using marker assisted selection.
      The development and initial physiologic screening of two inbred consomic rat
      panels on two genetic backgrounds (44 strains) is well underway. The primary uses
      of consomic strains are: (1) to assign traits and quantitative trait loci (QTL)
      to chromosomes by surveying the panel of strains with substituted chromosomes;
      (2) to rapidly develop congenic strains over a narrow region using several
      approaches described in this review and perform F2 linkage studies to
      positionally locate QTL in a fixed genetic background. In addition, consomic
      strains overcome many of the problems encountered with segregating crosses where,
      even if linkage is found, each individual in the cross is genetically unique and
      the combination of genes cannot be reproduced or studied in detail. Consomic
      strains provide greater statistical power to detect linkage than traditional F2
      crosses because of their fixed genetic backgrounds, and can produce sufficient
      numbers of genetically identical rats to validate the relationship between a
      trait and a particular chromosome. These strains allow studies to be performed in
      a replicative or longitudinal manner to elucidate in greater detail the
      sequential changes responsible for the observed phenotypes of these animals, and
      they enable one to assess the impact of a causal gene region in a genome by
      allowing comparisons of the effect of replacement of a specific chromosome upon a
      disease susceptible or resistant genomic background. Consomics can be used to
      quickly develop multiple chromosome substitution models to investigate gene-gene
      interactions of complex traits or diseases. Finally, they often provide the best
      available inbred control strain for particular physiological comparisons with the
      inbred parental strains. Consomic rat strains are proving to be a unique
      scientific resource that greatly extends our understanding of genes and complex
      normal and pathological function.

PMID- 14678491
TI  - Functional genomics in rodent models of hypertension.
AB  - Inbred strains of rodents have been used to study mammalian physiology and
      pathophysiology in an attempt to understand the contribution of genes in the
      pathogenesis of the disease process. In this review we focus on experimental
      animal models to identify quantitative trait loci (QTL) and possible strategies
      for identifying underlying genetic determinants responsible for hypertension.
      Confirmation of the existence of the QTL and dissection of the implicated region
      can be undertaken by production of either recombinant inbred, consomic or
      congenic strains. Despite complex interactions and the relatively few confirmed
      causative genes underlying QTL, recent developments in rat genome resources and
      advancement in statistical and bioinformatic methods will facilitate the
      identification of major gene(s) responsible for complex, polygenic traits.

PMID- 14678492
TI  - Functional expression of TASK-1/TASK-3 heteromers in cerebellar granule cells.
AB  - TASK-1 and TASK-3 are functional members of the tandem-pore K+ (K2P) channel
      family, and mRNAs for both channels are expressed together in many brain regions.
      Although TASK-1 and TASK-3 subunits are able to form heteromers when their
      complementary RNAs are injected into oocytes, whether functional heteromers are
      present in the native tissue is not known. Using cultured cerebellar granule (CG)
      neurones that express mRNAs of both TASK-1 and TASK-3, we studied the presence of
      heteromers by comparing the sensitivities of cloned and native K+ channels to
      extracellular pH (pHo) and ruthenium red. The single-channel conductance of TASK
      1, TASK-3 and a tandem construct (TASK-1/TASK-3) expressed in COS-7 cells were
      14.2 +/- 0.4, 37.8 +/- 0.7 and 38.1 +/- 0.7 pS (-60 mV), respectively. TASK-3 and
      TASK-1/TASK-3 (and TASK-3/TASK-1) displayed nearly identical single-channel
      kinetics. TASK-3 and TASK-1/TASK-3 expressed in COS-7 cells were inhibited by 26
      +/- 4 and 36 +/- 2 %, respectively, when pHo was changed from 8.3 to 7.3. In
      outside-out patches from CG neurones, the K+ channel with single channel
      properties similar to those of TASK-3 was inhibited by 31 +/- 7 % by the same
      reduction in pHo. TASK-3 and TASK-1/TASK-3 expressed in COS-7 cells were
      inhibited by 78 +/- 7 and 3 +/- 4 %, respectively, when 5 microm ruthenium red
      was applied to outside-out patches. In outside-out patches from CG neurones
      containing a 38 pS channel, two types of responses to ruthenium red were
      observed. Ruthenium red inhibited the channel activity by 77 +/- 5 % in 42 % of
      patches (range: 72-82 %) and by 5 +/- 4 % (range: 0-9 %) in 58 % of patches. When
      patches contained more than three 38 pS channels, the average response to
      ruthenium red was 47 +/- 6 % inhibition (n= 5). These electrophysiological
      studies show that native 38 pS K+ channels of the TASK family in cultured CG
      neurones consist of both homomeric TASK-3 and heteromeric TASK-1/TASK-3.

PMID- 14678493
TI  - Transference of recombinant VE-cadherin cytoplasmic domain alters endothelial
      junctional integrity and porcine microvascular permeability.
AB  - VE-cadherin constitutes endothelial adherens junctions through a homophilic
      binding of its extracellular domain and by the anchoring of its intracellular
      domain to actin cytoskeleton via catenins. The aim of this study was to determine
      the functional importance of VE-cadherin-cytoskeleton association in the
      maintenance of endothelial junctional integrity. A recombinant VE-cadherin
      cytoplasmic domain (rVE-cad CPD) was expressed in E. coli and purified through Ni
      NTA spin columns. Immunoprecipitation assays showed that rVE-cad CPD was able to
      bind beta-catenin in vitro and to compete with endogenous VE-cadherin for binding
      of beta-catenin in human umbilical vein endothelial cells. A significant increase
      in the transendothelial flux of albumin was observed in the endothelial cell
      monolayers transfected with rVE-cad CPD. Importantly, transfection of rVE-cad CPD
      into intact isolated coronary venules markedly elevated the albumin permeability
      of the venular endothelium. In addition, immunofluorescence microscopic analysis
      revealed a conformational change of VE-cadherin from a uniform, continuous
      distribution along the cell membrane under control conditions to a diffuse,
      stitch-like pattern after rVE-cad CPD transfection. The effects were likely due
      to an attenuated anchorage of endogenous VE-cadherin to the cytoskeleton, as
      evidenced by a decreased partitioning of VE-cadherin in the detergent-insoluble
      cytoskeletal pool. The results suggest that the intracellular association of VE
      cadherin with beta-catenin-linked cytoskeleton is essential to the maintenance of
      endothelial junctional integrity and microvascular permeability.

PMID- 14678494
TI  - Evidence of porcine and human endothelium activation by cancer-associated
      carbohydrates expressed on glycoproteins and tumour cells.
AB  - It is well established that after metastatic cancer cells escape the primary
      tumour and enter the circulation, their interactions with microvascular
      endothelium of a target organ constitute an essential rate-limiting step in
      haematogenous cancer metastasis. However, the physiological and biochemical
      processes supporting neoplastic cell arrest and retention in the microcirculation
      are still poorly understood. In this study, we present experimental evidence that
      microvascular endothelium of metastasis-prone tissues undergoes activation in
      response to desialylated cancer-associated carbohydrate structures such as
      Thomsen-Friedenreich (TF) antigen (Galbeta1-3GalNAc) expressed on circulating
      glycoproteins and neoplastic cells. The metastasis-associated endothelium
      activation, manifested by marked increase in endothelial cell surface galectin-3
      expression, causes gradual decrease in cancer cell velocities (from 72 x 10(2)+/-
      33 x 10(2) microm s-1 to 7.6 x 10(2)+/- 1.9 x 10(2) microm s-1, mean +/-s.d.)
      accompanied by a corresponding increase in the percentage of rolling cells (from
      3.3%+/- 1.2% to 24.3%+/- 3.6%, mean +/-s.d.), and results in human breast and
      prostate carcinoma cell arrest and retention in the microvasculature. This
      process, which could be of high importance in haematogenous cancer metastasis,
      was inhibited efficiently by an anti-TF antigen function-blocking antibody.
      Carbohydrate-mediated endothelial activation could be a process of physiological
      significance as it probably occurs in the interactions between a variety of
      circulating constituents and the vessel wall.

PMID- 14678495
TI  - Signalling pathway of nitric oxide in synaptic GABA release in the rat
      paraventricular nucleus.
AB  - In the paraventricular nucleus (PVN) of the hypothalamus, nitric oxide (NO)
      inhibits sympathetic outflow through increased GABA release. However, the signal
      transduction pathways involved in its action remain unclear. In the present
      study, we determined the role of cGMP, soluble guanylyl cyclase, and protein
      kinase G in the potentiating effect of NO on synaptic GABA release to spinally
      projecting PVN neurones. The PVN neurones were retrogradely labelled by a
      fluorescent tracer injected into the thoracic spinal cord of rats. Whole-cell
      voltage-clamp recordings were performed on labelled PVN neurones in the
      hypothalamic slice. Bath application of the NO donor, S-nitroso-N-acetyl
      penicillamine (SNAP), reproducibly increased the frequency of miniature GABAergic
      inhibitory postsynaptic currents (mIPSCs) without changing the amplitude and the
      decay time constant. Neither replacement of Ca2+ with Co2+ nor application of
      Cd2+ to block the Ca2+ channel altered the effect of SNAP on mIPSCs. Also, the
      effect of SNAP on mIPSCs was not significantly affected by thapsigargin, a Ca2+
      ATPase inhibitor that depletes intracellular Ca2+ stores. Application of a
      membrane-permeant cGMP analogue, pCPT-cGMP, mimicked the effect of SNAP on mIPSCs
      in the presence of a phosphodiesterase inhibitor, IBMX. Furthermore, both the
      soluble guanylyl cyclase inhibitor, ODQ, and the specific protein kinase G
      inhibitor, Rp pCPT cGMP, abolished the effect of SNAP on mIPSCs. Thus, these data
      provide substantial new information that NO potentiates GABAergic synaptic inputs
      to spinally projecting PVN neurones through a cGMP-protein kinase G pathway.

PMID- 14678496
TI  - Pacemaker channels in mouse thalamocortical neurones are regulated by distinct
      pathways of cAMP synthesis.
AB  - A crucial aspect of pacemaker current (Ih) function is the regulation by cyclic
      nucleotides. To assess the endogenous mechanisms controlling cAMP levels in the
      vicinity of pacemaker channels, Ih regulation by G-protein-coupled
      neurotransmitter receptors was studied in mouse thalamocortical neurones.
      Activation of beta-adrenergic receptors with (-)-isoproterenol (Iso) led to a
      small steady enhancement of Ih amplitude, whereas activation of GABAB receptors
      with (+/-)-Baclofen (Bac) reduced Ih, consistent with an up- and down-regulation
      of basal cAMP levels, respectively. In contrast, a transient (taudecay,
      approximately 200 s), supralinear up-regulation of Ih was observed upon
      coapplication of Iso and Bac that was larger than that observed with Iso alone.
      This up-regulation appeared to involve a cAMP synthesis pathway distinct from
      that recruited by Iso, as it was associated with a reversible acceleration in Ih
      activation kinetics and an occlusion of modulation by photolytically released
      cAMP, yet showed an 11 mV as opposed to a 6 mV positive shift in the activation
      curve and an at least seven-fold increase in duration. GABA, in the presence of
      the GABAA antagonist picrotoxin, mimicked, whereas N-ethylmaleimide, an inhibitor
      of Gi-proteins, blocked the up-regulation, supporting a requirement for GABAB
      receptor activation in the potentiation. Activation of synaptic GABAB responses
      via stimulation of inhibitory afferents from the nucleus reticularis potentiated
      Iso-induced increments in Ih, suggesting that synaptically located receptors
      couple positively to cAMP synthesis induced by beta-adrenergic receptors. These
      findings indicate that distinct pathways of cAMP synthesis target the pacemaker
      current and the recruitment of these may be controlled by GABAergic activity
      within thalamic networks.

PMID- 14678497
TI  - Ventilatory responses and carotid body function in adult rats perinatally exposed
      to hyperoxia.
AB  - Hypoxia increases the release of neurotransmitters from chemoreceptor cells of
      the carotid body (CB) and the activity in the carotid sinus nerve (CSN) sensory
      fibers, elevating ventilatory drive. According to previous reports, perinatal
      hyperoxia causes CSN hypotrophy and varied diminishment of CB function and the
      hypoxic ventilatory response. The present study aimed to characterize the
      presumptive hyperoxic damage. Hyperoxic rats were born and reared for 28 days in
      55%-60% O2; subsequent growth (to 3.5-4.5 months) was in a normal atmosphere.
      Hyperoxic and control rats (born and reared in a normal atmosphere) responded
      with a similar increase in ventilatory frequency to hypoxia and hypercapnia. In
      comparison with the controls, hyperoxic CBs showed (1) half the size, but
      comparable percentage area positive to tyrosine hydroxylase (chemoreceptor cells)
      in histological sections; (2) a twofold increase in dopamine (DA) concentration,
      but a 50% reduction in DA synthesis rate; (3) a 75% reduction in hypoxia-evoked
      DA release, but normal high [K+]0-evoked release; (4) a 75% reduction in the
      number of hypoxia-sensitive CSN fibers (although responding units displayed a
      nearly normal hypoxic response); and (5) a smaller percentage of chemoreceptor
      cells that increased [Ca2+]1 in hypoxia, although responses were within the
      normal range. We conclude that perinatal hyperoxia causes atrophy of the CB-CSN
      complex, resulting in a smaller number of chemoreceptor cells and fibers.
      Additionally, hyperoxia damages O2-sensing, but not exocytotic, machinery in most
      surviving chemoreceptor cells. Although hyperoxic CBs contain substantially
      smaller numbers of chemoreceptor cells/sensory fibers responsive to hypoxia they
      appear sufficient to evoke normal increases in ventilatory frequency.

PMID- 14678498
TI  - Calmodulin kinase is functionally targeted to the action potential plateau for
      regulation of L-type Ca2+ current in rabbit cardiomyocytes.
AB  - L-type Ca2+ current (ICa-L) triggers Ca2+ release from the sarcoplasmic reticulum
      (SR) and both SR and ICa-L are potential sources of intracellular Ca2+ (Ca2+i)
      for feedback regulation of ICa-L. Ca2+i bound to calmodulin (Ca2+-CaM) can
      inhibit ICa-L, while Ca2+-CaM can also activate Ca2+-CaM-dependent protein kinase
      II (CaMK) to increase ICa. However, it is not known whether ICa-L or the SR is
      the primary source of Ca2+ for ICa-L regulation. The L-type Ca2+ channel C
      terminus is implicated as a critical transduction element for ICa-L responses to
      Ca2+-CaM and CaMK, and the C terminus undergoes voltage-dependent steric changes,
      suggesting that Ca2+i control of ICa-L may also be regulated by cell membrane
      potential. We developed conditions to separately test the relationship of Ca2+
      CaM and CaMK to ICa-L and SR Ca2+i release during voltage clamp conditions
      modelled upon time and voltage domains relevant to the cardiac action potential.
      Here we show that CaMK increases ICa-L after brief positive conditioning pulses,
      whereas Ca2+-CaM reduces ICa-L over a broad range of positive and negative
      conditioning potentials. SR Ca2+ release was required for both Ca2+-CaM and CaMK
      ICa-L responses after strongly positive conditioning pulses (+10 and +40 mV),
      while Ca2+i from ICa-L was sufficient for Ca2+-CaM during weaker depolarizations.
      These findings show that ICa-L responses to CaMK are voltage dependent and
      suggest a new model of L-type Ca2+ channel regulation where voltage-dependent
      changes control ICa-L responses to Ca2+-CaM and CaMK signalling.

PMID- 14678499
TI  - The hippocampal intrinsic network oscillator.
AB  - Oscillatory activity characterizes the activity of the hippocampus in vivo;
      however, the underlying mechanism remains unknown. It is also known that during
      oscillations the number of action potentials provided by the principal cells is
      surprisingly low, and it is still an open question how oscillations can emerge
      under such constraints. One suggestion is that the discharge activity of
      inhibitory cells takes this function; however, this has been found, in my
      previous studies, not to be the case for cholinergically mediated and
      intrinsically generated hippocampal oscillations. This study identifies the
      hippocampal intrinsic network oscillator and the interactions which underlie the
      concurrent expression of cholinergically mediated theta (4-15 Hz) and gamma (20
      80 Hz) oscillations. A particular axonal network that involves the hippocampal
      associative pathway, shown to consist of axonal collaterals of CA2 and some CA3
      pyramidal cells, forms the oscillator core element. It is functionally activated
      via two cholinergically mediated reactions. First, direct activation of CA2 and
      CA3 pyramidal cells to discharge. Second, enhancement of gap junction-mediated
      axo-axonic interactions among axons of the core element and associated axons of
      interneurones, which together form the full oscillator. With these two reactions
      it is possible to explain the rhythmicities and patterns of activity, under the
      condition of a low number of action potentials. The discharge of CA3 pyramidals
      serves mainly as a trigger, while firing by CA2 pyramidals, and to a lesser
      degree by CA3 pyramidals, maintains the oscillatory activity. The cholinergically
      mediated 2-fold increase in axonal gap junction communication between cells
      serves two functions: (a) creation of specific activation pathways to produce the
      rhythmicities and patterns, and (b) formation of a reverberatory system that
      extends the time during which the sparsely generated action potentials can
      interact in the network, thereby providing a new source of action potentials,
      critical for the expression of oscillatory activity.

PMID- 14678501
TI  - Placental vascular endothelial growth factor receptor system mRNA expression in
      pigs selected for placental efficiency.
AB  - Selecting Yorkshire breeding stock for increased placental efficiency (PE; piglet
      weight divided by its placental weight) results in larger litters (i.e.
      approximately 3 more piglets litter-1) and reduced placental sizes. Placental
      vessel density increases progressively after day 50 of gestation in the pig, and
      is positively correlated with PE and placental expression of vascular endothelial
      growth factor (VEGF), a potent angiogenic and permeability factor. To elicit its
      vascular effects, VEGF must bind to its receptors (R), VEGF-R1 and VEGF-R2. The
      objective of this study was to compare placental and endometrial blood vessel
      density and placental VEGF, VEGF-R1 and VEGF-R2 mRNA expression in day 70 and 90
      conceptuses from Yorkshire females selected for high PE, low PE, and from
      unselected controls. A greater (P < 0.05) PE was observed for conceptuses in the
      high PE selection group when compared to the low PE selection group. Placental
      blood vessel density increased (P < 0.05) from day 70 to 90 (1.8 +/- 0.1 versus
      2.8 +/- 0.2) in association with increases (P < 0.05) in placental VEGF mRNA
      expression. No selection group differences were observed in expression of VEGF,
      VEGF-R1, or VEGF-R2 on day 70. By day 90, however, placentae of conceptuses from
      the high PE group expressed greater (P < 0.05) amounts of VEGF and VEGF-R1 mRNA
      than the unselected controls and the low PE group. These data demonstrate that
      increased placental expression of the VEGF receptor system is associated with
      increased placental vascular density observed with the advancement of gestation
      in the pig. Although placental blood vessel density was not increased in the high
      PE selection group, elevated levels of the VEGF receptor system suggest an effect
      on increasing placental and endometrial blood vessel permeability and/or
      proximity in the high PE group.

PMID- 14678500
TI  - Quantal transmission at mossy fibre targets in the CA3 region of the rat
      hippocampus.
AB  - Recent anatomical evidence that inhibitory interneurones receive approximately 10
      times more synapses from mossy fibres than do principal neurones (Acsady et al.
      1998) has led to the re-examination of the extent to which interneurones are
      involved in CA3 network excitability. Although many of the anatomical and
      physiological properties of mossy fibre-CA3 interneurone synapses have been
      previously described (Acsady et al. 1998; Toth et al. 2000), an investigation
      into the quantal nature of transmission at this synapse has not yet been
      conducted. Here, we employed variance-mean (VM) analysis to compare the release
      probability, quantal size (q) and number of release sites (n) at mossy fibre
      target neurones in CA3. At six of seven interneurone synapses in which a high
      concentration of Ca2+ was experimentally imposed, the variance-mean relationship
      could be approximated by a parabola. Estimates of n were 1-2, and the weighted
      release probability in normal Ca2+ conditions ranged from 0.34 to 0.51. At
      pyramidal cell synapses, the variance-mean relationship approximated a linear
      relationship, suggesting that release probability was significantly lower. The
      weighted quantal amplitude was similar at interneurone synapses and pyramidal
      cell synapses, although the variability in quantal amplitude was larger at
      interneurone synapses. Mossy fibre transmission at CA3 interneurone synapses can
      be explained by a lower number of release sites, a broader range of release
      probabilities, and larger range of quantal amplitudes than at CA3 pyramidal
      synapses. Finally, quantal events on to interneurones elicited spike
      transmission, owing in part to the more depolarized membrane potential than
      pyramidal cells. These results suggest that although mossy fibre synapses on to
      pyramidal cells are associated with a larger number of release sites per synapse,
      the higher connectivity, higher initial release probability, and larger relative
      impact per quantum on to CA3 interneurones generate strong feedforward inhibition
      at physiological firing frequencies of dentate granule cells. Given the central
      role of CA3 interneurones in mossy fibre synaptic transmission, these details of
      mossy fibre synaptic transmission should provide insight into CA3 network
      dynamics under both physiological and pathophysiological circumstances.

PMID- 14678502
TI  - Activity of dorsal raphe cells across the sleep-waking cycle and during cataplexy
      in narcoleptic dogs.
AB  - Cataplexy, a symptom associated with narcolepsy, represents a unique dissociation
      of behavioural states. During cataplectic attacks, awareness of the environment
      is maintained, as in waking, but muscle tone is lost, as in REM sleep. We have
      previously reported that, in the narcoleptic dog, noradrenergic cells of the
      locus coeruleus cease discharge during cataplexy. In the current study, we report
      on the activity of serotonergic cells of the dorsal raphe nucleus. The discharge
      patterns of serotonergic dorsal raphe cells across sleep-waking states did not
      differ from those of dorsal raphe and locus coeruleus cells recorded in normal
      rats, cats and monkeys, with tonic discharge in waking, reduced activity in non
      REM sleep and cessation of activity in REM sleep. However, in contrast with locus
      coeruleus cells, dorsal raphe REM sleep-off neurones did not cease discharge
      during cataplexy. Instead, discharge continued at a level significantly higher
      than that seen in REM sleep and comparable to that seen in non-REM sleep. We also
      identified several cells in the dorsal raphe whose pattern of activity was the
      opposite of that of the presumed serotonergic cells. These cells were maximally
      active in REM sleep and minimally active in waking and increased activity during
      cataplexy. The difference between noradrenergic and serotonergic cell discharge
      profiles in cataplexy suggests different roles for these cell groups in the
      normal regulation of environmental awareness and muscle tone and in the
      pathophysiology of narcolepsy.

PMID- 14678503
TI  - Control of human mandibular posture during locomotion.
AB  - Mandibular movements and masseter muscle activity were measured in humans during
      hopping, walking and running to determine whether reflexes contribute to the
      maintenance of jaw position during locomotion. In initial experiments, subjects
      hopped so that they landed either on their toes or on their heel. Landing on the
      toes provoked only small mandibular movements and no reflex responses in the
      masseter electromyogram (EMG). Landing on the heels with the jaw muscles relaxed
      caused the mandible to move vertically downwards relative to the maxilla, and
      evoked a brisk reflex response in the masseter at monosynaptic latency. Neither
      this relative movement of the mandible nor the reflex was seen when the teeth
      were clenched: hence the reflex is not the result of vestibular activation during
      head movement. The same variables were measured in a second series of experiments
      while subjects stood, walked and ran at various speeds and at various
      inclinations on a treadmill. During walking, the vertical movements of the head
      and therefore the mandible were slow and small, and there was no tonic masseter
      EMG or gait-related activity in the jaw-closing muscles. When subjects ran, the
      vertical head and jaw movement depended on the running speed and the inclination
      of the treadmill. Landing on the heels induced larger movements than landing on
      the toes. About 10 ms after each foot-strike, the mandible moved downwards
      relative to the maxilla, thereby stretching the jaw-closing muscles and
      activating them at segmental reflex latency. This caused the mandible to move
      back upwards. The strength of the reflex response was related to the speed and
      amplitude of the vertical jaw movement following landing. It is concluded that,
      during walking, the small, slow movements of the mandible relative to the maxilla
      are subthreshold for stretch reflexes in the jaw muscles: i.e. the mandible is
      supported by visco-elasticity of the soft tissues in the masticatory system.
      However, the brisker downward movements of the mandible after heel-landing during
      hopping and running evoke segmental reflex responses which contribute to the
      active maintenance of the posture of the mandible. This is a unique demonstration
      of how a stretch reflex operates to maintain posture under entirely natural
      conditions.

PMID- 14678504
TI  - Mechanosensitive duodenal afferents contribute to vagal modulation of
      inflammation in the rat.
AB  - Noxious stimuli inhibit inflammation by activating neuroendocrine stress axes, an
      effect that is potently attenuated by ongoing activity in subdiaphragmatic vagal
      afferents. Because this vagal afferent activity is carried in the coeliac and
      coeliac accessory branches of the subdiaphragmatic vagus, we tested the
      hypothesis that the activity arises from vagal afferents that innervate a
      proximal segment of the gastrointestinal tract. Surgical removal of the duodenum,
      but not the stomach, produces a marked (six orders of magnitude) leftward shift
      in the dose-response curve for intraplantar capsaicin-induced inhibition of
      synovial plasma extravasation induced by the potent inflammatory mediator
      bradykinin, in the knee joint; this is similar in magnitude to the inhibition
      produced by subdiaphragmatic or by coeliac plus coeliac accessory branch
      vagotomy. Fasting, to unload mechanically sensitive polymodal afferents in the
      proximal gastrointestinal tract, produces a similar leftward shift in the dose
      response curve for the inhibitory effect of capsaicin, an effect that is reversed
      by balloon distension in the duodenum in fasted rats, while balloon distension
      postvagotomy had no effect. These results suggest that activation of mechanically
      sensitive vagal afferents in the duodenum contributes vagal afferent activity
      that modulates neuroendocrine control of the inflammatory response.

PMID- 14678505
TI  - Evidence for peripheral plasticity in human odour response.
AB  - Of those people who are anosmic to androstenone, a proportion can acquire
      sensitivity to it by repeated exposure and even those who are able to smell it
      can lower their threshold with this treatment. Using olfactory threshold testing,
      intranasal electrophysiology and EEG we show for the first time that: (1) the
      subjects' detection threshold is proportional to the amplitude of the olfactory
      evoked potential (EOG) recorded inside the nose; (2) the EOG amplitude is
      correlated with the amplitude of the olfactory event-related potential (OERP)
      recorded on the scalp; and (3) with repetitive exposure, human subjects acquire a
      reduced threshold for androstenone and, as they do so, their EOG and OERP
      increase. These observations support the existence of odourant-specific
      plasticity in the peripheral olfactory system.

PMID- 14678506
TI  - Graphical representation and multicomponent analysis of single-frequency
      fluorescence lifetime imaging microscopy data.
AB  - Graphical representation of fluorescence lifetime imaging microscopy data
      demonstrates that a mixture of two components with single exponential decays can
      be resolved by single frequency measurements. We derive a method based on linear
      fitting that allows the calculation of the fluorescence lifetimes of the two
      components. We show that introduction of proper error-weighting results in a non
      linear method that is mathematically identical to a global analysis algorithm
      that was recently derived. The graphical approach was applied to cellular data
      obtained from a lifetime-based phosphorylation assay for the epidermal growth
      factor receptor and yielded results similar to those obtained by a global
      analysis algorithm.

PMID- 14678507
TI  - Oriented immobilization of Pseudomonas putida putidaredoxin at a gold (111)
      buffer interface: a real time scanning tunnelling microscopy study.
AB  - A scanning tunnelling microscopy study of adsorption of wild-type Pseudomonas
      putida putidaredoxin at a gold (111)-buffer interface has been made in real time.
      Reversible adsorption has been observed reflecting weak interaction of the wild
      type protein with a gold (111) electrode. A genetically engineered mutant, C73S
      D58C, which contains a surface thiol, has been used for 'immobilization' and
      'orientated adsorption' on the gold surface. The implication of such orientated
      immobilization in development of a bio-electrode surface has been predicted.

PMID- 14678508
TI  - Measurement of specimen-induced aberrations of biological samples using phase
      stepping interferometry.
AB  - Confocal or multiphoton microscopes, which deliver optical sections and three
      dimensional (3D) images of thick specimens, are widely used in biology. These
      techniques, however, are sensitive to aberrations that may originate from the
      refractive index structure of the specimen itself. The aberrations cause reduced
      signal intensity and the 3D resolution of the instrument is compromised. It has
      been suggested to correct for aberrations in confocal microscopes using adaptive
      optics. In order to define the design specifications for such adaptive optics
      systems, one has to know the amount of aberrations present for typical
      applications such as with biological samples. We have built a phase stepping
      interferometer microscope that directly measures the aberration of the wavefront.
      The modal content of the wavefront is extracted by employing Zernike mode
      decomposition. Results for typical biological specimens are presented. It was
      found for all samples investigated that higher order Zernike modes give only a
      small contribution to the overall aberration. Therefore, these higher order modes
      can be neglected in future adaptive optics sensing and correction schemes
      implemented into confocal or multiphoton microscopes, leading to more efficient
      designs.

PMID- 14678509
TI  - SNOM and AFM microscopy techniques to study the effect of non-ionizing radiation
      on the morphological and biochemical properties of human keratinocytes cell line
      (HaCaT).
AB  - In this study we have employed atomic force microscopy (AFM) and scanning near
      field optical microscopy (SNOM) techniques to study the effect of the interaction
      between human keratinocytes (HaCaT) and electromagnetic fields at low frequency.
      HaCaT cells were exposed to a sinusoidal magnetic field at a density of 50 Hz, 1
      mT. AFM analysis revealed modification in shape and morphology in exposed cells
      with an increase in the areas of adhesion between cells. This latter finding was
      confirmed by SNOM indirect immunofluorescence analysis performed with a
      fluorescent antibody against the adhesion marker beta4 integrin, which revealed
      an increase of beta4 integrin segregation in the cell membrane of 50-Hz exposed
      cells, suggesting that a higher percentage of these cells shows a modified
      pattern of this adhesion marker.

PMID- 14678510
TI  - phiFLIM: a new method to avoid aliasing in frequency-domain fluorescence lifetime
      imaging microscopy.
AB  - In conventional wide-field frequency-domain fluorescence lifetime imaging
      microscopy (FLIM), excitation light is intensity-modulated at megahertz
      frequencies. Emitted fluorescence is recorded by a CCD camera through an image
      intensifier, which is modulated at the same frequency. From images recorded at
      various phase differences between excitation and intensifier gain modulation, the
      phase and modulation depth of the emitted light is obtained. The fluorescence
      lifetime is determined from the delay and the decrease in modulation depth of the
      emission relative to the excitation. A minimum of three images is required, but
      in this case measurements become susceptible to aliasing caused by the presence
      of higher harmonics. Taking more images to avoid this is not always possible
      owing to phototoxicity or movement. A method is introduced, phiFLIM, requiring
      only three recordings that is not susceptible to aliasing. The phase difference
      between the excitation and the intensifier is scanned over the entire 360 degrees
      range following a predefined phase profile, during which the image produced by
      the intensifier is integrated onto the CCD camera, yielding a single image. Three
      different images are produced following this procedure, each with a different
      phase profile. Measurements were performed with a conventional wide-field
      frequency-domain FLIM system based on an acousto-optic modulator for modulation
      of the excitation and a microchannel-plate image intensifier coupled to a CCD
      camera for the detection. By analysis of the harmonic content of measured signals
      it was found that the third harmonic was effectively the highest present. Using
      the conventional method with three recordings, phase errors due to aliasing of up
      to +/- 29 degrees and modulation depth errors of up to 30% were found. Errors in
      lifetimes of YFP-transfected HeLa cells were as high as 100%. With phiFLIM, using
      the same specimen and settings, systematic errors due to aliasing did not occur.

PMID- 14678511
TI  - Analysis of boron-10 in soft tissue by dynamic secondary ion mass spectrometry.
AB  - We report here a preliminary study in which dynamic secondary ion mass
      spectrometry (SIMS) has provided images of boron-10 (10B) in biological tissue as
      used in research into boron neutron capture therapy. Cultured tumour cells
      incubated in media containing known concentrations of a 10B-containing compound,
      p-boronophenylalanine (BPA), and intracranial tumour tissue from animals
      previously injected with BPA were analysed by an in-house constructed SIMS.
      Investigations were conducted in positive secondary ion detection mode using a 25
      keV, 5-nA gallium primary ion source. For calibration purposes, tissue standards
      were also analysed and their boron-to-carbon signal ratios correlated to bulk
      boron concentrations measured by inductively coupled plasma atomic emission
      spectroscopy (ICP-AES). Ion maps of 10B, 12C, 23Na and 39K showing gross tissue
      and cell features were acquired. SIMS and ICP-AES standard measurements were in
      good agreement. Tissue regions with high or low 10B concentrations were
      identified along with 10B hotspots in normal brain areas. Cultured cells revealed
      the intracellular localization of 10B. SIMS is capable of producing images
      showing the distribution of 10B at p.p.m. levels in cells and in normal and
      tumour-bearing brain tissue.

PMID- 14678512
TI  - Optimizing imaging parameters for the separation of multiple labels in a
      fluorescence image.
AB  - A theoretical analysis is presented on how to separate the contributions from
      individual, simultaneously present fluorophores in a spectrally resolved image.
      Equations are derived that allow the calculation of the signal-to-noise ratio of
      the estimates for such contributions, given the spectral information on the
      individual fluorophores, the excitation wavelengths and intensities, and the
      number and widths of the spectral detection channels. We then ask how such
      imaging parameters have to be chosen for optimal fluorophore separation. We
      optimize the signal-to-noise ratio or optimize a newly defined 'figure of merit',
      which is a measure of efficiency in the use of emitted photons. The influence of
      photobleaching on the resolution and on the choice of imaging parameters is
      discussed, as well as the additional resolution gained by including fluorescence
      lifetime information. A surprisingly small number of spectral channels are
      required for an almost optimal resolution, if the borders of these channels are
      optimally selected. The detailed consideration of photobleaching is found to be
      essential, whenever there is significant bleaching. Consideration of fluorescence
      lifetime information (in addition to spectral information) improves results,
      particularly when lifetimes differ by more than a factor of two.

PMID- 14678513
TI  - Freeze-substitution and low-temperature embedding of dairy products for
      transmission electron microscopy.
AB  - Dairy products are comprised largely of fat, air and water, which makes it
      difficult to preserve their ultrastructure for electron microscopy. Keeping the
      samples frozen throughout fixation and embedding protects the structure and
      distribution of the components of emulsions and foams. Therefore, dairy products
      were freeze-substituted and embedded at low temperature (-20 degrees C) to
      prepare them for transmission electron microscopy. Whipped cream, ice cream mix
      and dairy/non-dairy mixed systems were frozen by plunging in propane, at its
      boiling point (-187 degrees C). Ice cream, because it is already frozen, was
      fractured into 1-mm3 pieces in liquid nitrogen and then added to frozen fixative
      (-196 degrees C). Fixative solution consisted of glutaraldehyde, osmium tetroxide
      and uranyl acetate dissolved in either methanol or acetone. When material was to
      be stained after sectioning the fixative was limited to glutaraldehyde in
      methanol. The temperature was increased step-wise from -80 to -20 degrees C.
      Solvent was replaced with resin; the polar resin Lowicryl HM4, the non-polar
      resin Lowicryl HM20, LR White and LR Gold were tested. Samples were embedded and
      polymerized at -20 degrees C using ultraviolet light to cross-link the resin.
      Methanol proved to be the most effective solvent for substituting the ice; the
      hydrophobic resin Lowicryl HM20 was the most effective resin for retaining fat
      structure following osmium fixation.

PMID- 14678514
TI  - Fluctuation analysis of mitochondrial NADH fluorescence signals in confocal and
      two-photon microscopy images of living cardiac myocytes.
AB  - A fluctuation analysis was performed on the reduced nicotine adenine dinucleotide
      (NADH) fluorescence signal from resting rabbit myocytes using confocal and two
      photon microscopy. The purpose of this study was to establish whether any co
      ordinated biochemical processes, such as binding, metabolism and inner
      mitochondrial membrane potential, were contributing to NADH signal fluctuations
      above background instrument noise. After a basic characterization of the
      instrument noise, time series of cellular NADH fluorescence images were collected
      and compared with an internal standard composed of NADH in the bathing medium.
      The coefficient of variation as a function of mean signal amplitude of cellular
      NADH fluorescence and bathing media NADH was identical even as a function of
      temperature. These data suggest that the fluctuations in cellular NADH
      fluorescence in resting myocytes are dominated by sampling noise of these
      instruments and not significantly modified by biological processes. Further
      analysis revealed no significant spatial correlations within the cell, and
      Fourier analysis revealed no coherent frequency information. These data suggest
      that the impact of biochemical processes, which might affect cellular NADH
      fluorescence emission, are either too small in magnitude, occurring in the wrong
      temporal scale or too highly spatially localized for detection using these
      standard optical microscopy approaches.

PMID- 14678515
TI  - An easy and versatile embedding method for transverse sections.
AB  - In several research areas, transverse sections are indispensable for studying
      structural aspects of specimens. However, the oriented embedding of small
      cylindrical samples can become problematic, especially when transverse sections
      at right angles to the main axis of the object are desired. Here, we describe an
      easy and low-cost technique for oriented embedding of small (psi < 500 micro m)
      as well as of larger specimens (psi > 500 micro m). The usefulness of the
      technique is demonstrated for roots and stamens of Arabidopsis thaliana and for
      adventitious roots of Asplenium demerkense, as examples of small and larger
      cylindrical samples, respectively. Furthermore, several types of resin (glycol
      methacrylate, epoxy and acrylic resins) were successfully tested, showing the
      applicability of the technique for light and electron microscopy and for
      immunolocalizations. In conclusion, the principle of the technique can be
      extended to several resins and a wide variety of specimen types, such as stems,
      leaves and textile fibres. The originality of the technique lies in its
      simplicity combined with its high efficiency to produce well-oriented transverse
      sections.

PMID- 14678516
TI  - High-pressure freezing of epithelial cells on sapphire coverslips.
AB  - Rapid freezing of cell monolayers at ambient pressure is limited regarding the
      thickness of ice crystal damage-free freezing. The specific freezing conditions
      of the cells under investigation are decisive for the success of such methods.
      Improved reproducibility of results could be expected by cryoimmobilization at
      high pressure because this achieves a greater thickness of adequate freezing. In
      a novel approach, we tested the suitability of sapphire discs as cell substrata
      for high-pressure freezing. Frozen samples on sapphire were subjected to freeze
      substitution while in the same flat sample holders as used for high-pressure
      freezing. We obtained cells that displayed an excellent preservation of fine
      structure. Because sapphire is a tissue culture substratum suitable for light
      microscopy, its use in combination with high-pressure freezing could become a
      powerful tool in correlative studies of cell dynamics at light and electron
      microscopic levels.

PMID- 14678517
TI  - Alteration of the fragile histidine triad gene early in carcinogenesis: an
      update.
AB  - An association between common chromosome fragile sites and frequent chromosomal
      deletions in cancer has been observed and led to the hypothesis that genes at
      fragile sites may play a role in tumor development. In 1996, the human fragile
      histidine triad gene, FHIT, was identified by positional cloning at 3p14.2, a
      chromosomal region spanning the carcinogen-sensitive, common fragile site FRA3B.
      FHIT gene is lost and inactivated in a large fraction of tumors and early in
      carcinogenesis. A group of ancestral cancerous cells that carry FHIT alterations,
      expanding in succeeding cell generations, exhibits a hallmark in carcinogenesis
      scenario.

PMID- 14678518
TI  - Clinical applications of DNA microarray analysis.
AB  - Microarray technology provides a revolutionary macro-genetic and bioinformatic
      rich platform for understanding human diseases. DNA microarrays facilitate the
      study of complex diseases, enabling several observations simultaneously that can
      become foundations for newer hypotheses-shifting us towards a non-reductionist
      approach to biological phenomenon. This appears of particular value for
      scientific and clinical dissection of tumor pathologies. Despite the tremendous
      potential presented by microarray technology for the investigation of disease,
      concrete insights and advances that translate to the clinical setting are only
      recently beginning to be tapped. Here, we discuss specific examples of how
      microarray technology is being integrated into our ever-evolving approach to
      clinical disease. We focus on molecular strategies for (a) disease
      classification, (b) disease outcome, and (c) disease mechanisms.

PMID- 14678519
TI  - Small cell lung cancer: from molecular biology to novel therapeutics.
AB  - Small cell lung cancer (SCLC) is an aggressive tumor which metastasizes early.
      Patients with this disease have a poor prognosis even with immediate treatment.
      Because of the aggressive nature of this disease, all aspects of this tumor are
      studied extensively. This review will provide an update of the biology of SCLC at
      both the molecular and cellular levels. Cellular pathways and their relationship
      to cellular function will also be discussed. Treatment of both primary limited-
      and extensive-stage diseases as well as recurrent disease will be discussed
      including chemotherapy, thoracic radiotherapy, and surgery. The role of novel
      therapeutics being investigated will also be addressed.

PMID- 14678520
TI  - Regulation of cathepsin B and L expression in vitro in gastric cancer tissues by
      egg cystatin.
AB  - BACKGROUND: Degradation of the basement membrane and surrounding extracellular
      matrix is likely to represent a key step in cancer invasion and metastasis. The
      purpose of this study was to determine whether gastric cancer tissues demonstrate
      higher cysteine proteases activities: cathepsins B and L during cancer
      progression in compression with non-cancerous tissues. METHODS: We measured the
      expression of both cathepsins B and L in 30 patients with gastric cancer tissues
      and non-cancerous tissues activities by a fluorescence assay and
      immunohistochemical staining. We attempted to regulate cathepsin B and L
      expression using egg white cystatin. RESULTS: The activities of cathepsins B and
      L were significantly higher in cancerous than in non-cancerous tissues (P </=
      0.0001). Activities of these enzymes decreased 18-fold after treatment of tissue
      homogenates with 5 nM of purified egg white cystatin. Immunohistochemical
      staining was significant and positive expression of low molecular weight cystatin
      was observed on the tumor cell surface in gastric carcinoma. It was found that
      non-cancerous tissues (control) were not stained with anti-egg white antibody.
      CONCLUSION: Our experiment demonstrated that the cysteine peptidases cathepsins B
      and L may be useful for the early detection of gastric cancer. The results
      suggest that addition of egg white cystatin reduces the activities of cathepsins
      B and L to that of non-cancerous values.

PMID- 14678521
TI  - Laser-assisted microdissection applied to frozen surgical pathologic specimens -
      methodological aspects on RT-PCR.
AB  - Laser-assisted microdissection has become a unique technique for an accurate gene
      expression profiling analysis in human tissues. The introduction of this approach
      requires the development of a reliable, efficient, and reproducible procedure for
      tissue processing. We report a systematic evaluation of the different relevant
      steps required to obtain sufficient quantity and good quality RNA for reverse
      transcriptase-polymerase chain reaction when using frozen surgical pathologic
      tissues as starting material. We propose an optimized and very efficient method
      with respect to time and effort that can easily be put into practice in research
      laboratory as well as in any pathology laboratory.

PMID- 14678522
TI  - Inhibition of indoleamine 2,3-dioxygenase suppresses NK cell activity and
      accelerates tumor growth.
AB  - Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolizing enzyme, is induced
      under various pathological conditions, including viral and bacterial infection,
      allograft rejection, cerebral ischemia, and tumor growth. We have previously
      reported that the expression of IDO mRNA was increased in some clinical cases of
      hepatocellular carcinoma in which the recurrence-free survival rate in these IDO
      positive patients was significantly higher than that in patients without IDO mRNA
      induction in tumors. Additionally, IDO expressed in tumors was localized not to
      the tumor cells but instead to tumor-infiltrating cells by immunohistochemistry.
      In this study, in order to elucidate the mechanisms underlying anti-tumor effect
      of IDO, we investigated whether IDO inhibitor (1-methyl-dl-tryptophan, 1MT)
      affects the growth of subcutaneous B16 tumors in mice. Subsequently, the activity
      of natural killer (NK) cells was investigated under the conditions of inhibited
      IDO activity in vivo and in vitro. IDO mRNA expression of B16 cells, B16
      subcutaneous tumor, sprenocytes of mice, and human NK cells were studied by
      reverse transcription-polymerase chain reaction. B16 subcutaneous tumor growth
      with or without IDO inhibition was observed and cytotoxic activity of NK cells
      were investigated under the conditions of inhibited IDO activity in vivo and in
      vitro. IDO mRNA was expressed in B16 subcutaneous tumor, splenocytes of tumor
      bearing mice, co-cultured splenocytes with B16, and human NK cells. On day 14,
      after injection of B16 melanoma cells, the sizes of tumors in IDO-inhibited mice
      were significantly larger than those in control mice. The cytotoxic activity of
      mice NK cells was reduced by IDO inhibition in vivo. In vitro inhibition of IDO,
      NK activity was reduced in dose-dependent manner of 1MT. In conclusion, these
      results indicated that IDO plays an important role in anti-tumor immunity by
      regulating cytotoxic activity of NK cells.

PMID- 14678523
TI  - Vanadium suppresses sister-chromatid exchange and DNA-protein crosslink formation
      and restores antioxidant status and hepatocellular architecture during 2
      acetylaminofluorene-induced experimental rat hepatocarcinogenesis.
AB  - Vanadium is an important regulator of cellular growth, differentiation, and cell
      death, and thus has received increasing attention to be an effective cancer
      chemopreventive agent. In the present study, attempts have been made to
      investigate the in vivo antineoplastic effect of this micronutrient at the 0.5
      ppm dosage in drinking water, by monitoring hepatic nodulogenesis and
      hepatocellular phenotype followed by antioxidant status and atomic absorption
      spectrometric estimation of some essential biometals during the multistage of
      carcinogenesis induced by 2-acetylaminofluorene (2-AAF; 0.05% in basal diet).
      Finally, sister-chromatid exchange (SCE) and DNA-protein crosslink (DPC)
      formation, as potential biomarkers were estimated to find out the suppressive
      effect of vanadium at the molecular level. The results showed that vanadium
      administration throughout the experiment reduced the relative liver weight,
      nodular incidence (48.40%), total number, and multiplicity (63.91%), and altered
      the size of visible persistent nodules (PNs) with concurrent restoration of
      hepatic glutathione (P < 0.01), glutathione-S-transferase (P < 0.001) and
      manganese-dependent superoxide dismutase (P < 0.001) activities as well as,
      hepatic zinc and copper contents (P < 0.001) when compared to the carcinogen
      control. Moreover, vanadium treatment significantly reduced SCE frequency
      (50.24%) and DPC coefficient (P < 0.001; 21.30%). Our results, thus, strongly
      suggest that supplementary vanadium at a dose of 0.5 ppm, when administered
      continuously throughout the study, than administered either in the initiation or
      promotion phase alone, is very much effective in suppressing neoplastic
      transformation during 2-AAF-induced in vivo rat hepatocarcinogenesis.

PMID- 14678525
TI  - Mycoplasma genitalium: the aetiological agent of urethritis and other sexually
      transmitted diseases.
AB  - Mycoplasma genitalium was first isolated in 1980 from two of 13 men with non
      gonococcal urethritis (NGU). It shares several features with M. pneumoniae, a
      recognized respiratory tract pathogen. It is extremely difficult to isolate by
      culture. The development of sensitive and specific polymerase chain reaction
      (PCR) assays in the early 1990s made clinical studies possible and a significant
      number of publications have shown a strong association between M. genitalium and
      NGU, independent of Chlamydia trachomatis. The purpose of this review is to
      evaluate the currently available information on the associations between M.
      genitalium and urogenital tract infections in men and women and assess their
      fulfilment of the Henle-Koch postulates. It is concluded that there is very
      strong evidence that M. genitalium is a cause of NGU in men and cervicitis in
      women. Evidence for upper genital tract infections in women has begun to accrue,
      but further studies are needed. The optimal treatment of M. genitalium infections
      remains to be determined, but antibiotics of the macrolide group appear to be
      more active than tetracyclines.

PMID- 14678526
TI  - Radiodermatitis: state of the art.

PMID- 14678527
TI  - Seborrheic dermatitis.
AB  - Seborrheic dermatitis is a common inflammation of the skin, occurring most often
      on the face, scalp and chest. It is closely related to infantile seborrheic
      dermatitis, or diaper rash. Seborrheic dermatitis is particularly common in
      patients with Parkinson's disease or with HIV/AIDS. The recent resurgence of
      interest in Malassezia yeasts has revived the old hypothesis that seborrheic
      dermatitis is caused by an altered relationship between these skin commensals and
      the host. Moreover, the success of antifungal medications in treating seborrheic
      dermatitis provides new evidence for this view. LEARNING OBJECTIVE: Upon
      completing this paper, the reader should be aware of the clinical presentation of
      seborrheic dermatitis and which populations are at particular risk of developing
      this disorder. In addition, s/he will be aware of the role of Malassezia yeasts
      in seborrheic dermatitis and the way in which knowledge of the importance of
      these yeasts has altered the treatment of this disorder.

PMID- 14678528
TI  - Self-reported stress reactivity and psoriasis-related stress of Nordic psoriasis
      sufferers.
AB  - OBJECTIVES: The purpose of the study was to investigate the perceived influence
      of stress on psoriasis onset and disease severity in a large sample of psoriatics
      and to compare stress reactors and non-reactors with respect to psoriasis-related
      stress, disease severity, family history of psoriasis and sociodemographic
      factors. PATIENTS/METHODS: A total of 5795 members of the Nordic psoriasis
      associations and 702 patients recruited from Nordic dermatologists or university
      clinics were asked whether their first outbreak of psoriasis occurred during
      times of worry and stress. They were also asked to rate the degree to which their
      psoriasis was influenced by stress and to complete the Psoriasis Life Stress
      Index, the Psoriasis Disability Index and a number of additional questions
      concerning sociodemographic factors. RESULTS: Seventy-one per cent of the members
      and 66% of the patients reported that their psoriasis was exacerbated by stress,
      and 35% in both groups reported that the onset of their psoriasis occurred during
      a time of worry and stress. Stress reactors, scoring above the median on stress
      reactivity, reported greater disease severity, psoriasis-related stress and
      impairment of disease-related quality of life. They also reported more frequent
      use of tobacco, tranquillizers and antidepressants. More women than men were
      stress reactors, and stress reactors were more likely to have a family history of
      psoriasis. CONCLUSION: Our findings confirm and extend the results of previous
      studies and indicate that a subgroup of psoriatics may be more psychologically
      reactive to their disease and its influence on everyday life. Whether this group
      is also physiologically more reactive to psychosocial stress remains to be
      investigated.

PMID- 14678529
TI  - Profound inhibition of chronic itch induced by stimulation of thin cutaneous
      nerve fibres.
AB  - BACKGROUND: Despite the fact that severe itch is common in many dermatological
      diseases, the therapeutic arsenal against itching is limited. From
      neurophysiological experiments, using a new technique termed cutaneous field
      stimulation, it is known that acute itch can be effectively relieved by
      stimulation of cutaneous nociceptors. METHODS: We tested the effects of cutaneous
      field stimulation (25 min, 16 electrodes, 4 Hz per electrode, up to 0.8 mA) on
      chronic itch due to atopic dermatitis. Transcutaneous electrical nerve
      stimulation (100 Hz, up to 26 mA) was used for comparison. In 27 patients, itch
      was measured just prior to, during and at regular intervals up to 12 h after
      either type of treatment. RESULTS: Both treatments augmented the itch sensation
      during ongoing stimulation, presumably reflecting an altered sensory processing
      in the somatosensory pathways of chronic itch patients. However, after cessation
      of cutaneous field stimulation, but not transcutaneous electrical nerve
      stimulation, the itch sensation was significantly depressed for up to 7 h. The
      peak inhibitory effect (about 25% of control) was reached between 1 and 5 h
      poststimulation. Neither treatment had any significant effect on alloknesis, as
      measured before and 10 min after stimulation. CONCLUSION: It is concluded that
      cutaneous field stimulation strongly depresses chronic itch, and is a potentially
      useful symptomatic treatment of itch.

PMID- 14678531
TI  - Risk factors associated with onychomycosis.
AB  - OBJECTIVE: To examine possible risk factors related to onychomycosis. BACKGROUND:
      Onychomycosis is a common disease with multifactorial aetiology, but little is
      known about the risk factors for this disease. PATIENTS AND METHODS: Questions
      related to signs, symptoms and possible risk factors associated with
      onychomycosis were sent to 3992 persons aged 16 years and older selected randomly
      from the Icelandic National Registry. Patients with suspected onychomycosis,
      based on photographs, were offered mycological examination. Data from the
      questionnaire and the results of mycological examination were used to calculate
      the odds ratio (OR) for several factors that might be associated with
      onychomycosis. RESULTS: Two thousand four hundred and eighty-six subjects
      responded to the questionnaire. Prevalence for mycologically determined
      onychomycosis was 11.1% in the Icelandic population. A history of the following
      factors more than doubled the risk of onychomycosis: cancer (OR 3.44; 95% CI 1.15
      10.35), psoriasis (OR 2.44; 95% CI 1.61-3.72), tinea pedis interdigitalis (OR
      3.93; 95% CI 3.11-4.95), the moccasin form of tinea pedis (OR 4.26; 94% CI 3.34
      5.45), parents with onychomycosis (OR 2.59; 95% CI 1.89-3.53), children with
      onychomycosis (OR 3.48; 95% CI 2.05-5.88), spouse with onychomycosis (OR 2.53;
      95% CI 1.72-3.72), regular swimming activity (OR 2.57; 95% CI 2.00-3.30) and age
      50 years or older (OR 2.74; 95% CI 2.19-3.42). CONCLUSIONS: Several risk factors
      are associated with onychomycosis. Knowledge of these risk factors is important
      when treating and educating patients with onychomycosis.

PMID- 14678530
TI  - Campaigning for melanoma prevention: a model for a health education program.
AB  - Melanoma incidence and mortality rates are rising in many countries. This has led
      to the development of a variety of education programs designed for either early
      detection of melanoma when it can be easily cured, or prevention by taking a long
      term approach. Australia has been leading in these areas running programs such as
      Slip! Slop! Slap! for over 20 years. Data now show that attitudes towards
      sunlight and suntans have changed substantially. Sunburn rates have decreased as
      photoprotection has increased. Melanoma mortality rates are decreasing in the
      younger cohorts as a result of earlier detection of tumours that can be easily
      cured. Finally, incidence rates for melanoma in the younger cohorts are starting
      to level out and go down. Thus health education programs can be successful if
      they are well-designed and evaluated. In Australia we are now extending these
      programs beyond melanoma and into education programs on other common skin
      diseases such as acne, atopic dermatitis, warts, tinea, and a variety of other
      common conditions, depending on the level at which the education program is being
      delivered. This is the first time that coordinated public education programs on
      skin diseases, apart from skin cancer, have occurred anywhere in the world.

PMID- 14678532
TI  - Antioxidant activity of topically applied lycopene.
AB  - BACKGROUND: Ultraviolet (UV) rays cause depletion of the antioxidant substances
      contained in the epidermis. This is the rationale for the use of topical
      antioxidant substances. METHODS: We studied the protective activity against UV
      radiation of a product based on lycopene and a product containing a mixture of
      vitamins E and C. Photostimulation was applied with a solar simulator and the
      cutaneous response was evaluated instrumentally. RESULTS: The lycopene-based
      product had a much greater protective ability than the product containing the
      mixture of vitamins. CONCLUSIONS: Lycopene has suitable characteristics to be
      used successfully in the prevention of cutaneous damage by free radicals. Its
      antioxidant ability is probably due to its high reductive power.

PMID- 14678533
TI  - The significance of immunohistochemistry in the skin pathergy reaction of
      patients with Behcet's syndrome.
AB  - BACKGROUND: Behcet's syndrome is a chronic systemic immuno-inflammatory disorder
      affecting multiple organs with generalized vasculitis of arteries and veins.
      Although the aetiology is still unknown, endothelial dysfunction is one of the
      most prominent features in Behcet's syndrome. The skin pathergy reaction (SPR) is
      a non-specific hyperreactive lesion formation that is one of the major features
      and diagnostic criteria of the disease. It develops after 24-48 h at the site of
      the needle-prick, especially in the exacerbation period, and it is very similar
      to the erythematous papules or pustules that appear spontaneously in patients
      with Behcet's syndrome. Therefore, an investigation into the formation of the SPR
      lesion may contribute to the pathophysiology of skin lesions of this unique
      disorder. OBJECTIVE: To evaluate the immunological features of SPR formation by
      assessing the immunohistochemical staining of cell adhesion molecules and
      endothelial growth factor markers such as E-selectin, P-selectin and endoglin (CD
      105). METHODS: Patients with Behcet's syndrome showing positive (n = 15) or
      negative (n = 10) SPR and 15 age- and sex-matched hospital-based healthy control
      subjects from a similar ethnic background were included in this study. Patients
      were divided into active and inactive stage by clinical findings and acute-phase
      reactant parameters including erythrocyte sedimentation rate (ESR) and neutrophil
      count. Punch biopsy specimens were obtained both from the lesion site on the
      forearms at 48 h and from normal skin approximately 5 cm adjacent to the SPR
      site. A biopsy was also obtained from the test application site in Behcet's
      syndrome patients with negative SPR and healthy volunteers. Biopsy specimens were
      then evaluated by immunohistochemical staining. RESULTS: Immunohistochemical
      examination demonstrated a mixed inflammatory cell infiltrate around the vessels
      and skin appendages that extended somewhat into the deep dermis. A positive
      segmental staining of E-selectin and P-selectin was noted in the endothelial
      cells of biopsies obtained from the patients with positive SPR. A positive
      segmental staining of CD 105 in the endothelial cells was also observed in the
      same group of patients. However, the immunostaining of the same markers was found
      to be negative in the biopsies obtained from normal skin of SPR-positive
      patients, SPR-negative patients and healthy control subjects. Both acute-phase
      reactant levels were significantly higher in the active stage than in inactive
      patients or healthy controls. CONCLUSION: Interaction of cellular adhesion
      molecules together with endothelial proliferation may play an important role in
      the formation of SPR lesions in patients with Behcet's syndrome. The involvement
      of the vascular endothelium in a large number of diseases including Behcet's
      syndrome supports the importance of vascular-specific adhesion molecules for
      their aetiopathogenesis.

PMID- 14678534
TI  - Nailfold digital capillaroscopy in 447 patients with connective tissue disease
      and Raynaud's disease.
AB  - The presence of megacapillaries and a decreased capillary density are the
      hallmarks of the scleroderma capillary pattern, which can be detected by nailfold
      capillarmicroscopy. One hundred and eighty-six patients with Raynaud's
      phenomenon, 65 cases with undifferentiated connective tissue disease (UCTD), 47
      patients with systemic lupus erythematosus (SLE), 26 patients with
      dermato/polymyositis, 14 with rheumatoid arthritis, seven cases with primary
      Sjogren's syndrome and 102 patients with systemic sclerosis (SSc) were
      investigated. Of the 16 patients with diffuse cutaneous SSc and the 86 limited
      cutaneous SSc cases, 14 (87.5%) and 53 (61.6%) showed the scleroderma capillary
      pattern, respectively. Nine of the 65 (13.8%) cases with UCTD and 24 of the 186
      (12.9%) cases with Raynaud's phenomenon also exhibited the same pattern. Four of
      the 47 (8.5%) with SLE and seven of the 26 (26.9%) with dermato/polymyositis, and
      no patients with rheumatoid arthritis or Sjogren's syndrome, exhibited the
      scleroderma capillary pattern. The conclusion is that the scleroderma capillary
      pattern is often present in SSc and dermato/polymyositis. Furthermore, patients
      with Raynaud's phenomenon and UCTD may also occasionally exhibit this pattern.
      Therefore, capillarmicroscopy seems to be a useful tool for the early selection
      of those patients who are potential candidates for developing scleroderma
      spectrum disorders.

PMID- 14678535
TI  - Mast cells and IgE-containing cells in gastric mucosa of Helicobacter pylori
      infected and non-infected patients with chronic urticaria.
AB  - BACKGROUND: Several studies have indicated that antibiotic therapy aimed at
      eradication of Helicobacter pylori has effects on symptoms of chronic urticaria
      (CU) patients. However, the possible connections and pathomechanism by which H.
      pylori might be linked to CU have remained largely unknown. The IgE-mediated
      pathway might be a possible link between H. pylori infection and CU. We therefore
      clarified the role of H. pylori as an inducer of IgE response. MATERIALS AND
      METHODS: Gastroscopy was performed and mucosal biopsy specimens were taken to
      evaluate the histology, as well as the presence of H. pylori bacteria, mast cells
      and IgE-containing cells in the antral mucosa, in 21 CU patients. Controls (n =
      48) included 19 patients with lichen planus, nine patients with atopic dermatitis
      and 20 patients with no skin or allergic disease. RESULTS: The mean densities of
      IgE-containing cells were significantly higher in H. pylori-infected patients and
      in patients with skin disease compared to non-H. pylori-infected patients with no
      skin or allergic disease. No significant difference was found in the number of
      IgE-containing cells between H. pylori-infected and non-infected patients with
      CU. There was no significant difference in the mean densities of mast cells in
      the different patient groups. CONCLUSIONS: Our findings suggest that H. pylori
      gastritis leads to increased IgE production. However, we could not show a
      significant difference in IgE staining between H. pylori-infected and non
      infected patients with CU.

PMID- 14678536
TI  - Antifungal activity of Thymus oils and their major compounds.
AB  - The increasing recognition and importance of fungal infections, the difficulties
      encountered in their treatment and the increase in resistance to antifungals have
      stimulated the search for therapeutic alternatives. Essential oils have been used
      empirically. The essential oils of Thymus (Thymus vulgaris, T. zygis subspecies
      zygis and T. mastichina subspecies mastichina) have often been used in folk
      medicine. The aim of the present study was to evaluate objectively the antifungal
      activity of Thymus oils according to classical bacteriological methodologies -
      determination of the minimal inhibitory concentration (MIC) and the minimal
      lethal concentration (MLC) - as well as flow cytometric evaluation. The effect of
      essential oils upon germ tube formation, an important virulence factor, was also
      studied. The mechanism of action was studied by flow cytometry, after staining
      with propidium iodide. The chemical composition of the essential oils was
      investigated by gas chromatography (GC) and gas chromatography/mass spectroscopy
      (GC/MS). The antifungal activity of the major components (carvacrol, thymol, p
      cymene and 1,8-cineole) and also possible interactions between them were also
      investigated. The essential oils of T. vulgaris and T. zygis showed similar
      antifungal activity, which was greater than T. mastichina. MIC and MLC values
      were similar for all the compounds tested. At MIC values of the essential oils,
      propidium iodide rapidly penetrated the majority of the yeast cells, indicating
      that the fungicidal effect resulted primarily from an extensive lesion of the
      cell membrane. Concentrations below the MIC values significantly inhibited germ
      tube formation. This study describes the potent antifungal activity of the
      essential oils of Thymus on Candida spp., warranting future therapeutical trials
      on mucocutaneous candidosis.

PMID- 14678537
TI  - Report from Cavtat.

PMID- 14678538
TI  - Atypical pityriasis rosea and Hodgkin's disease.
AB  - Pityriasis rosea (PR)-like eruptions have been associated with several neoplasms
      and drugs. These eruptions may be atypical. To date, the association of Hodgkin's
      disease with PR-like eruptions has rarely been reported. We report a 37-year-old
      patient with clinical lesions of PR-like, systemic symptoms and
      lymphadenopathies, who was subsequently diagnosed with Hodgkin's disease.

PMID- 14678539
TI  - First case of Mycobacterium haemophilum infection in an AIDS patient in Italy.
AB  - Mycobacterium haemophilum, a strongly acid- and alcohol-fast bacillus belonging
      to the group of non-tuberculous mycobacteria was first described in 1978 as the
      cause of cutaneous ulcerating lesions in a woman with Hodgkin's disease.
      Infection due to M. haemophilum is rare but increasing in prevalence in
      immnunosuppressed subjects, particularly in patients with acquired
      immunodeficiency syndrome (AIDS) patients. The skin is the most common site of
      infection with erythematous or violaceous papules and/or nodules that are usually
      painless at first, but some elements develop into abscesses or ulcers that can
      become very painful. The incidence of M. haemophilum is unknown, but cases of
      infection have been reported in Australia, Canada, the United States, France,
      Israel, the United Kingdom and Taiwan; to date no cases have been reported in
      Italy, thus the case reported here is apparently the first one observed in our
      country.

PMID- 14678540
TI  - Blastic natural killer cell leukaemia with skin involvement: a case report.
AB  - Natural killer cell leukaemia is generally accompanied by extramedullary
      involvement. CD4+ natural killer cell leukaemia frequently manifests with
      cutaneous involvement. The disease pursues a very aggressive course with no long
      term survivors reported. We present a patient with CD4+ natural killer cell
      leukaemia with skin, bone marrow and peripheral blood involvement who is still on
      remission at the end of 2 years.

PMID- 14678542
TI  - Two cases of squamous cell carcinoma treated with topical imiquimod 5%.
AB  - We report the first two cases of squamous cell carcinoma successfully treated
      with imiquimod 5% cream as a monotherapy. Imiquimod is a new immunomodulating
      drug that is registered for genital HPV infection but has also shown good
      efficacy in several cutaneous malignancies.

PMID- 14678541
TI  - Acute pustulosis of the legs in diverticulitis with sigmoid stenosis: an overlap
      between bowel-associated dermatosis-arthritis syndrome and pustular pyoderma
      gangrenosum.
AB  - BACKGROUND: Bowel-associated dermatosis-arthritis syndrome denotes the occurrence
      of diarrhoea with arthritis and skin lesions related to bowel disease with or
      without bowel bypass. In this condition, the histological finding of cutaneous
      aseptic neutrophilic cell infiltrate is non-specific and common to a wide
      spectrum of neutrophilic dermatoses, including pyoderma gangrenosum. OBSERVATION:
      We describe a 78-year-old woman with fever, abdominal discomfort and arthralgias,
      who developed grouped pustular lesions on her shins with histologically
      spongiform pustule formation. Aetiological assessment disclosed diverticular
      disease with sigmoid stenosis. CONCLUSION: Although clinical and histological
      features in our case fit the diagnosis of bowel-associated dermatosis-arthritis
      syndrome, they may also correspond to a pustular variant of pyoderma gangrenosum.
      Our observation raises the question of the nosological classification of bowel
      associated dermatosis-arthritis syndrome within the spectrum of neutrophilic
      diseases.

PMID- 14678543
TI  - Plasma cell cheilitis.
AB  - Plasma cell cheilitis is a rare inflammatory disorder of the lip with a
      characteristic band-like infiltrate of plasma cells in the upper dermis.
      Differential diagnosis should consider allergic/irritant contact cheilitis,
      candidiasis, syphilis, Queyrat's erythroplasia, granulomatous cheilitis,
      plasmoacanthoma, plasmacytoma, squamous cell carcinoma and exfoliative or
      factitious cheilitis. We observed plasma cell cheilitis in a 60-year-old
      Caucasian female who had a partial response to topical steroids and oral
      griseofulvin.

PMID- 14678544
TI  - Cutaneous cryptococcus Laurentii infection in a human immunodeficiency virus
      negative subject.

PMID- 14678545
TI  - Tinea capitis by trichophyton violaceum in immuno-suppressed elderly man.

PMID- 14678546
TI  - Extensive verruca vulgaris at unusual sites in an immunocompetent adult.

PMID- 14678547
TI  - The evaluation of the effectiveness and side-effects of a 200-mg/day constant
      dose of cyclosporin in chronic plaque-type psoriasis: can a constant dose be an
      alternative?

PMID- 14678548
TI  - Fatal aplastic anaemia in a patient with clarithromycin-induced toxic epidermal
      necrolysis.

PMID- 14678549
TI  - Scabies in the elderly.

PMID- 14678550
TI  - Localized mucinosis subsequent to erysipelas.

PMID- 14678551
TI  - Bullous lichen sclerosus atrophicus.

PMID- 14678552
TI  - Thyroid function and autoimmunity in children and adolescents with vitiligo.

PMID- 14678553
TI  - UVB phototherapy for Pityriasis rosea.

PMID- 14678554
TI  - Pigment anomaly caused by calcipotriol in a subject with melanoma.

PMID- 14678555
TI  - Discoid lupus erythematosus: clinical and pathological study of 24 patients.

PMID- 14678556
TI  - Partial response to treatment with recombinant interferon-alpha2a in an adult
      patient with tufted angioma.

PMID- 14678557
TI  - CagA seropositivity in Helicobacter pylori positive patients with psoriasis.

PMID- 14678559
TI  - The study of expanded tri-lobed flap in a rabbit model: possible flap model in
      ear reconstruction?
AB  - BACKGROUND: Local flaps are widely used in reconstructive surgery. Tri-lobed skin
      flap is a relatively new flap and there has been no experimental model of this
      flap. This flap can be used for repair of full thickness defects in the face,
      ears and alar region. Based on the size of ears in a rabbit, we designed a model
      of ear reconstruction using expanded tri-lobed flap. Local flaps are more
      advantageous in that they provide excellent color and texture matching up with
      those of the face, adequately restore ear contour, place scars in a favorable
      location and ideally accomplish these goals in a single stage with minimal donor
      site morbidity. METHODS: Eight adult New Zealand rabbits were divided into two
      groups. 50 ml round tissue expander were implanted to four rabbits. After
      completion of the expansion, a superiorly based tri-lobed flap was elevated and a
      new ear was created from the superior dorsal skin of each rabbit. Scintigraphy
      with Technetium-99m pertecnetate was performed to evaluate flap viability.
      RESULTS: Subtotal flap necrosis was seen in all animals in non-expanded group.
      New ear in dimensions of the original ear was created in expanded group without
      complication. Perfusion and viability of the flaps were proved by Technetium-99m
      pertecnetate scintigraphy. CONCLUSION: According to our knowledge this study is
      the first to demonstrate animal model in tri-lobed flap. Also, our technique is
      the first application of the trilobed flap to the possible ear reconstruction. We
      speculated that this flap may be used mastoid based without hair, in human. Also,
      tri-lobed flap may be an alternative in reconstruction of cylindrical organs such
      as penis or finger.

PMID- 14678560
TI  - Inter-examiner reliability of the diagnosis of cervical pillar hyperplasia (CPH)
      and the correlation between CPH and spinal degenerative joint disease (DJD).
AB  - BACKGROUND: Cervical pillar hyperplasia (CPH) is a recently described phenomenon
      of unknown aetiology. Its clinical importance is poorly understood at the present
      time; therefore, the objective of this study was to determine (1) the inter
      examiner reliability of detecting CPH and (2) if there is a clinically important
      correlation (r > 0.4) between the number of cervical spine levels showing signs
      of degenerative joint disease (DJD) and CPH. METHODS: The sample consisted of 320
      radiographs of human male and female subjects who ranged from 40 to 79 years of
      age. The inter-examiner reliability of assessing the presence/absence of pillar
      hyperplasia was evaluated on 50 neutral lateral radiographs by two examiners
      using line drawings and it was quantified using the kappa coefficient of
      concordance. To determine the presence/absence of hyperplastic pillars as well as
      the presence/absence of DJD at each intervertebral disc and zygapophysial joint,
      320 AP open mouth, AP lower cervical and neutral lateral radiographs were then
      examined. The unpaired t-test at the 5% level of significance was performed to
      test for a statistically significant difference between the number of levels
      affected by DJD in patients with and without hyperplasia. The Spearman's rho at
      the 5% level of significance was performed to quantify the correlation between
      DJD and age. RESULTS: The inter-examiner reliability of detecting cervical pillar
      hyperplasia was moderate with a kappa coefficient of 0.51. The unpaired t-test
      indicated that there was no statistically significant difference (p > 0.05)
      between the presence/absence of cervical pillar hyperplasia and the number of
      levels affected by DJD in an age-matched population, regardless of whether all
      elements were considered together, or the discs and facets were analyzed
      separately. A Spearman correlation rank of 0.67 (p < 0.05) suggested a moderately
      strong correlation between the number of elements (i.e. discs/facets) affected,
      and the age of the individual. CONCLUSION: Cervical pillar hyperplasia is a
      reasonable concept that requires further research. Its evaluation is easy to
      learn and acceptably reliable. Previous research has suggested that CPH may
      affect the cervical lordosis, and therefore, alter biomechanics which may result
      in premature DJD. This current study, however, indicates that, globally, CPH does
      not appear to be related to the development of DJD.

PMID- 14678561
TI  - Racial differences in influenza vaccination among older Americans 1996-2000:
      longitudinal analysis of the Health and Retirement Study (HRS) and the Asset and
      Health Dynamics Among the Oldest Old (AHEAD) survey.
AB  - BACKGROUND: Influenza is a common and serious public health problem among the
      elderly. The influenza vaccine is safe and effective. METHODS: The purpose of the
      study was to determine whether frequencies of receipt vary by race, age group,
      gender, and time (progress from 1995/1996 to 2000), and whether any racial
      differences remain in age groups covered by Medicare. Subjects were selected from
      the Health and Retirement Study (HRS) (12,652 Americans 50-61 years of age (1992
      2000)) and the Asset and Health Dynamics Among the Oldest Old (AHEAD) survey
      (8,124 community-dwelling seniors aged 70+ years (1993-2000)). Using multivariate
      logistic regression, adjusting for potential confounders, we estimated the
      relationship between race, age group, gender, time and the main outcome measure,
      receipt of influenza vaccination in the last 2 years. RESULTS: There has been a
      clear increase in the unadjusted rates of receipt of influenza vaccination for
      all groups from 1995/1996 to 2000. However, the proportions immunized are 10-20%
      higher among White than among Black elderly, with no obvious narrowing of the
      racial gap from 1995/1996 to 2000. There is an increase in rates from age 50 to
      age 65. After age 70, the rate appears to plateau. In multivariate analyses, the
      racial difference remains after adjusting for a series of socioeconomic, health,
      and health care related variables. (HRS: OR = 0.63 (0.55-0.72), AHEAD: OR = 0.55
      (0.44-0.66)) CONCLUSIONS: There is much work left if the Healthy People 2010 goal
      of 90% of the elderly immunized against influenza annually is to be achieved.
      Close coordination between public health programs and clinical prevention efforts
      in primary care is necessary, but to be truly effective, these services must be
      culturally appropriate.

PMID- 14678562
TI  - An epidemiological study of pleuropulmonary paragonimiasis among pupils in the
      peri-urban zone of Kumba town, Meme Division, Cameroon.
AB  - BACKGROUND: Paragonimiasis have previously been reported in two zones of the
      Southwest Province of Cameroon including the Kupe mountain and Mundani foci. The
      aim of this study was to investigate the presence and epidemiology of
      paragonimiasis in the peri-urban zone of Kumba, Meme Division, located about 50
      km away from the Kupe mountain focus. METHODS: Pupils of several government
      primary schools in 5 villages around Kumba underwent both parasitologic and
      clinical investigations in search of signs and symptoms of paragonimiasis.
      Mycobacterium tuberculosis was also searched for in the differential diagnosis.
      Freshwater crabs from neighbouring streams in the five villages were dissected in
      search of paragonimus metacercariae. RESULTS: Out of a total of 1482 pupils
      examined in all five villages, 309 individuals (147 males and 162 females) were
      recruited for this study based on the presence of one or more signs or symptoms
      of paragonimiasis. Eggs of Paragonimus africanus were found in stools and/or
      sputum of pupils from all five villages, giving an overall paragonimus prevalence
      of 2.56%. There was no significant difference in the disease prevalence between
      the villages (Chi2 = 8.36, P = 0.08). The prevalence of Paragonimus africanus
      eggs amongst pupils with symptoms of paragonimiasis was 12.3% (38 of 309). Males
      were infected more than females (17.0% versus 8.0%), but the difference was not
      significant (Chi2 = 5.76, P = 0.16). All the 38 paragonimus egg positive subjects
      presented with cough, 23 (60.53%) complained of chest pain while 16 (42.11%) had
      haemoptysis. Stool examinations also detected some intestinal parasites including
      Ascaris lumbricoides (29.45%), Trichuris trichiura (6.47%), Necator americanus
      (2.27%), Strongyloides stercoralis (1.62%), Enterobius vermicularis (0.65%), and
      Entamoeba histolytica (4.53%). No case of M. tuberculosis was noted. Out of a
      total of 85 dissected crabs (Sudanonautes africanus), 6.02 % were infected with
      paragonimus metacercariae. CONCLUSION: In addition to the two previously
      described paragonimiasis foci of Kupe mountain and Mundani, the identification of
      autochthonous cases of paragonimiasis in the peri-urban zone of Kumba town, makes
      the South West Province the most endemic zone of paragonimiasis in Cameroon at
      present.

PMID- 14678563
TI  - A new growth chart for preterm babies: Babson and Benda's chart updated with
      recent data and a new format.
AB  - BACKGROUND: The Babson and Benda 1976 "fetal-infant growth graph" for preterm
      infants is commonly used in neonatal intensive care. Its limits include the small
      sample size which provides low confidence in the extremes of the data, the 26
      weeks start and the 500 gram graph increments. The purpose of this study was to
      develop an updated growth chart beginning at 22 weeks based on a meta-analysis of
      published reference studies. METHODS: The literature was searched from 1980 to
      2002 for more recent data to complete the pre and post term sections of the
      chart. Data were selected from population studies with large sample sizes.
      Comparisons were made between the new chart and the Babson and Benda graph. To
      validate the growth chart the growth results from the National Institute of Child
      Health and Human Development Neonatal Research Network (NICHD) were superimposed
      on the new chart. RESULTS: The new data produced curves that generally followed
      patterns similar to the old growth graph. Mean differences between the curves of
      the two charts reached statistical significance after term. Babson's 10th
      percentiles fell between the new data percentiles: the 5th to 17th for weight,
      the 5th and 15th for head circumference, and the 6th and 16th for length. The
      growth patterns of the NICHD infants deviated away from the curves of the chart
      in the first weeks after birth. When the infants reached an average weight of 2
      kilograms, those with a birthweight in the range of 700 to 1000 grams had
      achieved greater than the 10th percentile on average for head growth, but
      remained below the 3rd percentile for weight and length. CONCLUSION: The updated
      growth chart allows a comparison of an infant's growth first with the fetus as
      early as 22 weeks and then with the term infant to 10 weeks. Comparison of the
      size of the NICHD infants at a weight of 2 kilograms provides evidence that on
      average preterm infants are growth retarded with respect to weight and length
      while their head size has caught up to birth percentiles. As with all meta
      analyses, the validity of this growth chart is limited by the heterogeneity of
      the data sources. Further validation is needed to illustrate the growth patterns
      of preterm infants to older ages.

PMID- 14678564
TI  - The development of the Canberra symptom scorecard: a tool to monitor the physical
      symptoms of patients with advanced tumours.
AB  - BACKGROUND: Patients with advanced (incurable) tumours usually experience a
      diverse burden of symptoms. Although many symptom assessment instruments are
      available, we examined whether these addressed tumour-related symptoms. METHODS:
      We reviewed existing symptom assessment instruments and found a number of
      deficiencies such as instruments being too long or burdensome, too short, or
      measuring quality of life rather than tumour-related symptoms. Others focused on
      emotional, rather than physical symptoms. Therefore, we decided to devise a new
      symptom instrument. A list of 20 symptoms common in patients with advanced
      tumours generated from the literature and existing instruments, was ranked
      according to prevalence by 202 Australian clinicians. Following clinicians'
      responses, the list was revised and two severity assessment scales (functional
      severity and distress severity) added. The resultant 18-item list was assessed in
      44 outpatients with advanced tumours. RESULTS: Patient responses indicated that a
      shorter questionnaire of 11 items, reflecting three main symptom clusters,
      provided a good representation of physical symptoms. An additional symptom that
      is an important predictor of survival was added, making a 12-item questionnaire,
      which was entitled "The Canberra Symptom Scorecard" (CSS). For symptom severity,
      the distress severity scale was more appropriate than the functional severity
      scale. CONCLUSION: The CSS focuses on tumour-related physical symptoms. It is
      about to be assessed in patients with advanced tumours receiving palliative
      treatments, when it will also be validated against existing instruments.

PMID- 14678565
TI  - AnaBench: a Web/CORBA-based workbench for biomolecular sequence analysis.
AB  - BACKGROUND: Sequence data analyses such as gene identification, structure
      modeling or phylogenetic tree inference involve a variety of bioinformatics
      software tools. Due to the heterogeneity of bioinformatics tools in usage and
      data requirements, scientists spend much effort on technical issues including
      data format, storage and management of input and output, and memorization of
      numerous parameters and multi-step analysis procedures. RESULTS: In this paper,
      we present the design and implementation of AnaBench, an interactive, Web-based
      bioinformatics Analysis workBench allowing streamlined data analysis. Our
      philosophy was to minimize the technical effort not only for the scientist who
      uses this environment to analyze data, but also for the administrator who manages
      and maintains the workbench. With new bioinformatics tools published daily,
      AnaBench permits easy incorporation of additional tools. This flexibility is
      achieved by employing a three-tier distributed architecture and recent
      technologies including CORBA middleware, Java, JDBC, and JSP. A CORBA server
      permits transparent access to a workbench management database, which stores
      information about the users, their data, as well as the description of all
      bioinformatics applications that can be launched from the workbench. CONCLUSION:
      AnaBench is an efficient and intuitive interactive bioinformatics environment,
      which offers scientists application-driven, data-driven and protocol-driven
      analysis approaches. The prototype of AnaBench, managed by a team at the
      Universite de Montreal, is accessible on-line at:
      http://malawimonas.bcm.umontreal.ca:8091/anabench. Please contact the authors for
      details about setting up a local-network AnaBench site elsewhere.

PMID- 14678566
TI  - How do Zimbabweans value health states?
AB  - BACKGROUND: Quality of life weights based on valuations of health states are
      often used in cost utility analysis and population health measures. This paper
      reports on an attempt to develop quality of life weights within the Zimbabwe
      context. METHODS: 2,384 residents in randomly selected small residential plots of
      land in a high-density suburb of Harare valued descriptors of 38 health states
      based on different combinations of the five domains of the EQ-5D (mobility, self
      care, usual activities, pain or discomfort and anxiety or depression). The
      English version of the EQ-5D was used. The time trade-off method was used to
      determine the values, and 19,020 individual preferences for health states were
      analysed. A residual maximum likelihood linear mixed model was used to estimate a
      function for predicting the values of all possible combinations of levels on the
      five domains. The model was fit to a random subset of two-thirds of the
      observations, with the remaining observations reserved for analysis of predictive
      validity. The results were compared to a similar study undertaken in the United
      Kingdom. RESULTS: A credible model was developed to predict the values of states
      that were not valued directly. In the subset of observations reserved for
      validation, the mean absolute difference between predicted and observed values
      was 0.045. All domains of the EQ-5D were found to contribute significantly to the
      model, both at the moderate and severe levels. Severe pain was found to have the
      largest negative coefficient, followed by the inability to wash and dress
      oneself. CONCLUSION: Despite a generally lower education level than their
      European counterparts, urban Zimbabweans appear to value health states in a
      consistent manner, and the determination of a global method of establishing
      quality of life weights may be feasible and valid. However, as the relative
      weightings of the different domains, although correlated, differed from the
      standard set of weights recommended by the EuroQol Group, the locally determined
      coefficients should be used within the Zimbabwean context.

PMID- 14678567
TI  - Gonadotropin releasing hormone analogue (GnRHa) alters the expression and
      activation of Smad in human endometrial epithelial and stromal cells.
AB  - Gonadotropin releasing hormone analogues (GnRHa) are often used to regress
      endometriosis implants and prevent premature luteinizing hormone surges in women
      undergoing controlled ovarian stimulation. In addition to GnRH central action,
      the expression of GnRH and receptors in the endometrium implies an
      autocrine/paracrine role for GnRH and an additional site of action for GnRHa. To
      further examine the direct action of GnRH (Leuprolide acetate) in the
      endometrium, we determined the effect of GnRH on endometrial stromal (ESC) and
      endometrial surface epithelial (HES) cells expression and activation of Smads
      (Smad3, -4 and -7), intracellular signals activated by transforming growth factor
      beta (TGF-beta), a key cytokine expressed in the endometrium. The results show
      that GnRH (0.1 microM) increased the expression of inhibitory Smad7 mRNA in HES
      with a limited effect on ESC, while moderately increasing the common Smad4 and
      Smad7 protein levels in these cells (P < 0.05). GnRH in a dose--(0.01 to 10
      microM) and time--(5 to 30 min) dependent manner decreased the rate of Smad3
      activation (phospho-Smad3, pSmad3), and altered Smad3 cellular distribution in
      both cell types. Pretreatment with Antide (GnRH antagonist) resulted in further
      suppression of Smad3 induced by GnRH, with Antide inhibition of pSmad3 in ESC.
      Furthermore, co-treatment of the cells with GnRH + TGF-beta, or pretreatment with
      TGF-beta type II receptor antisense to block TGF-beta autocrine/paracrine action,
      in part inhibited TGF-beta activated Smad3. In conclusion, the results indicate
      that GnRH acts directly on the endometrial cells altering the expression and
      activation of Smads, a mechanism that could lead to interruption of TGF-beta
      receptor signaling mediated through this pathway in the endometrium.

PMID- 14678568
TI  - The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System:
      properties, applications, and interpretation.
AB  - The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System
      is a collection of health-related quality of life (HRQOL) questionnaires targeted
      to the management of chronic illness. The measurement system, under development
      since 1987, began with the creation of a generic CORE questionnaire called the
      Functional Assessment of Cancer Therapy-General (FACT-G). The FACT-G (now in
      Version 4) is a 27-item compilation of general questions divided into four
      primary QOL domains: Physical Well-Being, Social/Family Well-Being, Emotional
      Well-Being, and Functional Well-Being. It is appropriate for use with patients
      with any form of cancer, and extensions of it have been used and validated in
      other chronic illness condition (e.g., HIV/AIDS; multiple sclerosis; Parkinson's
      disease; rheumatoid arthritis), and in the general population. The FACIT
      Measurement System now includes over 400 questions, some of which have been
      translated into more than 45 languages. Assessment of any one patient is tailored
      so that the most-relevant questions are asked and administration time for any one
      assessment is usually less than 15 minutes. This is accomplished both by the use
      of specific subscales for relevant domains of HRQOL, or computerized adaptive
      testing (CAT) of selected symptoms and functional areas. FACIT questionnaires can
      be administered by self-report (paper or computer) or interview (face-to-face or
      telephone). Available scoring, normative data and information on meaningful
      change now allow one to interpret results in the context of a growing literature
      base.

PMID- 14678570
TI  - Construction and use of Plasmodium falciparum phage display libraries to identify
      host parasite interactions.
AB  - BACKGROUND: The development of Plasmodium falciparum within human erythrocytes
      induces a wide array of changes in the ultrastructure, function and antigenic
      properties of the host cell. Numerous proteins encoded by the parasite have been
      shown to interact with the erythrocyte membrane. The identification of new
      interactions between human erythrocyte and P. falciparum proteins has formed a
      key area of malaria research. To circumvent the difficulties provided by
      conventional protein techniques, a novel application of the phage display
      technology was utilised. METHODS: P. falciparum phage display libraries were
      created and biopanned against purified erythrocyte membrane proteins. The
      identification of interacting and in-frame amino acid sequences was achieved by
      sequencing parasite cDNA inserts and performing bioinformatic analyses in the
      PlasmoDB database. RESULTS: Following four rounds of biopanning, sequencing and
      bioinformatic investigations, seven P. falciparum proteins with significant
      binding specificity toward human erythrocyte spectrin and protein 4.1 were
      identified. The specificity of these P. falciparum proteins were demonstrated by
      the marked enrichment of the respective in-frame binding sequences from a fourth
      round phage display library. CONCLUSION: The construction and biopanning of P.
      falciparum phage display expression libraries provide a novel approach for the
      identification of new interactions between the parasite and the erythrocyte
      membrane.

PMID- 14678569
TI  - Aryl hydrocarbon receptor (AhR) agonists suppress interleukin-6 expression by
      bone marrow stromal cells: an immunotoxicology study.
AB  - BACKGROUND: Bone marrow stromal cells produce cytokines required for the normal
      growth and development of all eight hematopoietic cell lineages. Aberrant
      cytokine production by stromal cells contributes to blood cell dyscrasias.
      Consequently, factors that alter stromal cell cytokine production may
      significantly compromise the development of normal blood cells. We have shown
      that environmental chemicals, such as aromatic hydrocarbon receptor (AhR)
      agonists, suppress B lymphopoiesis by modulating bone marrow stromal cell
      function. Here, we extend these studies to evaluate the potential for two
      prototypic AhR agonists, 7,12-dimethylbenz [a]anthracene (DMBA) and 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), to alter stromal cell cytokine responses.
      METHODS: Bone marrow stromal cells were treated with AhR agonists and bacterial
      lipopolysaccharide (LPS) to mimic innate inflammatory cytokine responses and to
      study the effects of AhR ligands on those responses. Steady state cytokine RNA
      levels were screened by RNAse protection assays (RPA) and quantified by real-time
      PCR. Cytokine (IL-6) protein production was measured by ELISA. NF-kappaB EMSAs
      were used to study IL-6 transcriptional regulation. RESULTS: RPAs indicated that
      AhR+ bone marrow stromal cells consistently up-regulated genes encoding IL-6 and
      LIF in response to LPS, presumably through activation of Toll-like receptor 4.
      Pre-treatment with low doses of DMBA or TCDD selectively abrogated IL-6 gene
      induction but had no effect on LIF mRNA. Real-time-PCR indicated a significant
      inhibition of IL-6 mRNA by AhR ligands within 1 hour of LPS challenge which was
      reflected in a profound down-regulation of IL-6 protein induction, with DMBA and
      TCDD suppressing IL-6 levels as much as 65% and 88%, respectively. This potent
      inhibitory effect persisted for at least 72 hours. EMSAs measuring NF-kappaB
      binding to IL-6 promoter sequences, an event known to induce IL-6 transcription,
      indicated a significant decrease in the LPS-mediated induction of DNA-binding
      RelA/p50 and c-Rel/p50 heterodimers in the presence of DMBA. CONCLUSIONS: Common
      environmental AhR agonists can suppress the response to bacterial
      lipopolysaccharide, a model for innate inflammatory responses, through down
      regulation of IL-6, a cytokine critical to the growth of several hematopoietic
      cell subsets, including early B cells. This suppression occurs at least at the
      level of IL-6 gene transcription and may be regulated by NF-kappaB.

PMID- 14678573
TI  - Perspectives on Neuroscience and Behavior.

PMID- 14678571
TI  - Experiences of using an interactive audience response system in lectures.
AB  - BACKGROUND: Lectures are good for presenting information and providing
      explanations, but because they lack active participation they have been
      neglected. METHODS: Students' experiences were evaluated after exposing them to
      the use of voting during lectures in their paediatrics course. Questions were
      delivered to the students taking paediatrics course. Thirty-six students out of
      the total of 40 (90%) attended the opening lecture, at which the first survey
      concerning previous experiences of lectures was performed. Thirty-nine students
      (98%) answered the second series of questions at the end of the paediatrics
      course. RESULTS: Most of the students felt that voting improved their activity
      during lectures, enhanced their learning, and that it was easier to make
      questions during lectures than earlier. CONCLUSIONS: The students gained new,
      exciting insights much more often during the paediatrics course than before. We
      as teachers found that voting during lectures could easily overcome some of the
      obstacles of good lecturing.

PMID- 14678574
TI  - Disease Mechanisms in Neuroscience.

PMID- 14678575
TI  - Enhancing synaptic plasticity and memory: a role for small-conductance Ca(2+)
      activated K+ channels.
AB  - Calcium-activated potassium (K+) channels are distributed throughout the central
      nervous system as well as many other peripheral tissues and comprise three
      distinct classes of K+ channels: small conductance (SK), intermediate
      conductance, and large conductance. This update focuses on SK channels. Increases
      in cytosolic calcium in response to depolarization activate SK channels.
      Activation of these channels decreases neuronal excitability. In this review, the
      authors discuss the role of SK channels in the induction of synaptic plasticity
      and their influence on learning and memory. A testable model that synthesizes the
      current literature is offered, suggesting that SK channels represent an important
      regulator of synaptic plasticity and memory.

PMID- 14678576
TI  - Neural synchrony, axonal path lengths, and general anesthesia: a hypothesis.
AB  - Despite decades of research, the mechanism by which general anesthetics produce
      loss of consciousness remains mysterious. A clue may be provided by the evidence
      that synchronous firing of cortical neurons underlies higher forms of neural
      processing. In order for these synchrony codes to be precise, transmission time
      must be independent of path length over all the connected sites between any two
      cortical areas. Because path lengths vary, developmental mechanisms must
      compensate for the resulting delay variations. Delay variations could be detected
      by spike-timing-dependent cues and compensation implemented by systematic changes
      in axon diameter, myelin thickness, or internodal distance. Anesthetics have been
      shown to increase conduction velocity in myelinated fibers and may therefore
      disrupt path-length compensation by changing velocities by different amounts in
      different types of axon. This simple and testable theory explains why anesthetics
      interfere selectively with higher cognitive functions but leave those dominated
      by rate-based firing relatively intact.

PMID- 14678577
TI  - Animal models of cerebral neglect and its cancellation.
AB  - The purpose of this perspective is twofold: 1) to alert and inform the
      neurospychology and neurology communities on how animal models can improve our
      understanding of spatial neglect in humans, and 2) to serve as a guide to
      rehabilitation strategies. Spatial neglect is a neurological syndrome that is
      inextricably linked to the ability to overtly or covertly reorient attention to
      new loci. Literature describing variants of neglect leads to the perception of
      lesion-induced neglect as a uniquely human syndrome for which there are limited
      treatment options. To the contrary, neglect has been reversed in laboratory
      animals, and results show that adequate neural representations and motor
      mechanisms for reversal are present despite damaged or deactivated cerebral
      cortex. These results and conclusions provoke thought on strategies that can be
      employed on humans to cancel neglect, and they suggest that long-term
      amelioration of neglect can be induced by training of specific bypass circuits.

PMID- 14678578
TI  - D1 dopamine receptor supersensitivity in the dopamine-depleted striatum animal
      model of Parkinson's disease.
AB  - Dopamine acts in the striatum principally through the D1 and D2 dopamine receptor
      subtypes, which are segregated to the direct and indirect striatal projection
      neurons, respectively. As a consequence, degeneration of the dopamine input to
      the striatum results in opposing affects in these pathways. The resulting
      functional imbalance is thought to be responsible for the bradykinesia of
      Parkinson's disease, which may be temporarily normalized by dopamine replacement
      therapy. However, direct striatal projection neurons become irreversibly
      supersensitive to D1 dopamine receptor activation, despite the fact that there is
      an actual decrease in receptor number. Recent studies show that this D1 
      supersensitive response results from a switch from the normal D1-mediated
      activation of protein-kinase A to an aberrant activation of ERK1/2/MAPkinase.
      This switch in D1-receptor-mediated regulation of protein kinase systems
      responsible for neuronal plasticity is suggested to underlie dyskinesia produced
      by L-DOPA treatment of Parkinson's disease.

PMID- 14678579
TI  - Properties and mechanisms of LTP maintenance.
AB  - Memory is fundamentally important to everyday life, and memory loss has
      devastating consequences to individuals and society. Understanding the
      neurophysiological and cellular basis of memory paves the way for gaining
      insights into the molecular steps involved in memory formation, thereby revealing
      potential therapeutic targets for neurological diseases. For three decades, long
      term potentiation (LTP) has been the gold standard synaptic model for mammalian
      memory mechanisms, in large part because of its long-lasting nature. Here, the
      authors summarize the characteristics of LTP persistence in the dentate gyrus of
      the hippocampus, comparing this with other hippocampal subregions and neocortex.
      They consider how long LTP can last and how its persistence is affected by
      subsequent behavioral experiences. Next, they review the molecular mechanisms
      known to contribute to LTP induction and persistence, in particular the role of
      new gene expression and protein synthesis and how they may be associated with
      potential structural reorganization of the synapse. A temporal schema for the
      processes important for consolidating LTP into a persistent form is presented.
      The parallels between the molecular aspects of LTP and memory strongly support
      the continuation with LTP as a model system for studying the mechanisms
      underlying long-term memory consolidation and retention.

PMID- 14678580
TI  - Induced gamma-band activity and human brain function.
AB  - Oscillatory activity in the gamma-band range has been related both to gestalt
      perception and to cognitive functions such as attention, learning, and memory.
      After giving a brief account of recent findings from electroencephalography and
      intracortical recordings, the present review will focus on spectral activity in
      the magnetoencephalogram. Here, gamma-band effects are topographically more local
      and involve higher frequencies than in the electroencephalogram. Bottom-up-driven
      auditory spatial mismatch detection elicits gamma-band activity over posterior
      parietal cortex, whereas auditory pattern mismatch processing leads to gamma-band
      enhancements over anterior temporal and inferior frontal regions. These
      topographies support representations of auditory spatial and pattern information
      in the putative dual auditory "where" and "what" pathways, respectively. During
      top-down-guided auditory spatial and pattern-working memory tasks, prefrontal
      gamma-band increases are observed in addition to activations over putative
      auditory stream areas. Moreover, stimulus maintenance in working memory is
      accompanied by coherence increases between sensory and prefrontal regions. Gamma
      band topographies in magnetoencephalogram are highly comparable with hemodynamic
      brain imaging studies but yield additional information on the temporal dynamics
      of activations and connectivity patterns. In summary, magnetoencephalographic
      gamma-band activity revealed both local synchronization patterns and cortico
      cortical interactions accompanying cognitive processes at a good spatial and high
      temporal resolution.

PMID- 14678581
TI  - Glaucomatous optic neuropathy: when glia misbehave.
AB  - The loss of vision in the human eye disease, glaucoma, is due to degeneration of
      the axons of the retinal ganglion cells. In glaucoma, reactive astrocytes in the
      optic nerve head contain inducible nitric oxide synthase, which apparently
      produces excessive nitric oxide that damages the axons. The astrocytes respond to
      the elevated intraocular pressure that is characteristic of the disease. An
      important signal transduction pathway for the induction of nitric oxide synthase
      in response to pressure is the epidermal growth factor receptor tyrosine kinase.
      Pharmacological inhibition of the activity or the induction of inducible nitric
      oxide synthase may provide neuroprotection for the treatment of glaucoma.

PMID- 14678582
TI  - Disruption in the inhibitory architecture of the cell minicolumn: implications
      for autism.
AB  - The modular arrangement of the neocortex is based on the cell minicolumn: a self
      contained ecosystem of neurons and their afferent, efferent, and interneuronal
      connections. The authors' preliminary studies indicate that minicolumns in the
      brains of autistic patients are narrower, with an altered internal organization.
      More specifically, their minicolumns reveal less peripheral neuropil space and
      increased spacing among their constituent cells. The peripheral neuropil space of
      the minicolumn is the conduit, among other things, for inhibitory local circuit
      projections. A defect in these GABAergic fibers may correlate with the increased
      prevalence of seizures among autistic patients. This article expands on our
      initial findings by arguing for the specificity of GABAergic inhibition in the
      neocortex as being focused around its mini- and macrocolumnar organization. The
      authors conclude that GABAergic interneurons are vital to proper minicolumnar
      differentiation and signal processing (e.g., filtering capacity of the
      neocortex), thus providing a putative correlate to autistic symptomatology.

PMID- 14678583
TI  - Effectiveness of preventive human papillomavirus vaccination.
AB  - Infection with human papillomavirus (HPV) is one of the major preventable causes
      of cancer world-wide. Rapid increase in cervical cancer incidence also in some
      western countries with cervical cancer screening programmes is probably due to
      increase in background exposure to HPV in the young. HPV vaccines are in clinical
      trials and the results have been promising, but due to assortative transmission
      of the infection and multiple HPV types the effect of large-scale immunization on
      their spread will vary between different populations and by HPV type. Thus, it is
      difficult to predict the effect of vaccination on cancer incidence on the basis
      of efficacy trials only. In the following evaluation of population level,
      effectiveness of vaccination on cervical cancer incidence (1) and HPV prevalence
      (2) by combined cluster/individually randomized trials (1) and cluster/community
      randomized trials (2) are described.

PMID- 14678584
TI  - Effects of a change from an appointment service to a walk-in triage service at a
      sexual health centre.
AB  - A walk-in triage system (WITS) was introduced at Melbourne Sexual Health Centre
      in August 2001 as a result of the perceived need to increase access to the clinic
      for clients requiring immediate assessment. An audit of this alteration to clinic
      operation resulted in a significant increase in the number of new clients
      attending the clinic who were younger and less likely to report using condoms,
      substantial increases in the number of investigations ordered for bacterial
      sexually transmitted infections (STIs) and an increase in the detection of
      genital herpes and chlamydia. There are a number of possible explanations for
      these changes other than the change to clinic operation but these are less likely
      causes for the observed changes. Our findings should complement the other reasons
      to adopt a WITS system, such as improving access for those most in need and vital
      to reach if STI rates are to fall.

PMID- 14678585
TI  - Longstanding vulval problems and entry dyspareunia among STD-clinic visitors in
      Oslo-results from a cross-sectional study.
AB  - An increasing number of women with vulval problems and pain attend
      Olafiaklinikken, the centre for sexually transmitted infection (STI) in Oslo. The
      aim of the study was to investigate the prevalence of long-standing vulval
      problems and entry dyspareunia in a consecutive sample of STI-clinic visitors in
      Oslo. A self-administered questionnaire was distributed before and independent of
      the consultation. Response rate was 89.6% (502/560). Mean and median age were
      25.9 and 24.0 years respectively, range 16-65 years. Vulval soreness, burning,
      dryness and fissures present for at least three months were reported by 23.1%
      (116/502), entry dyspareunia by 6.9% (34/494). Independent risk factors for
      dyspareunia were a history of >/=4 treatments for vulvovaginal candidiasis during
      the last year, reported by 34.6%, odds ratio (OR) 4.45, 95% confidence interval
      (CI) 1.81-11.0, and a history of bacterial vaginosis, reported by 42.4%, OR 2.34,
      95% CI 1.11-4.92. Contraceptive methods, hygienic habits, a history of STIs,
      depression or sexual abuse were factors unrelated to longstanding symptoms.
      Investigation with regard to longstanding vulval problems and entry dyspareunia
      is required for a certain group of sexually transmitted disease-clinic visitors
      in Oslo, and referral to a special service for vulva patients would be beneficial
      for selected patients.

PMID- 14678586
TI  - Ethnic variation of the P53 codon 72 polymorphism, HPV persistence, and cervical
      cancer risk.
AB  - Association between the p53 codon 72 polymorphism and cervical cancer remains
      unresolved. We determined the association between the polymorphism and risk of
      human papillomavirus (HPV) persistence. The polymorphism was detected by
      restriction enzyme digestion following p53 amplification and HPV detection by the
      PGMY 09/11 primer set followed by reverse line blot hybridization: 3371 samples
      were analysed. HPV persistence was assessed on a subset of samples collected at
      baseline, four and 10 months (n =442). Highly significant differences were
      observed between ethnic groups (P <0.005). No associations were found between P53
      arginine and cytological grade in women infected with any HPV or any oncogenic
      HPV, despite adjustment for ethnicity. These results were sustained even when HPV
      negative women were used as controls. Persistence for any or oncogenic HPV
      infection was not associated with the polymorphism, irrespective or ethnicity
      adjustment. Our findings do not support a role for this polymorphism conferring
      elevated risk for HPV-related disease.

PMID- 14678587
TI  - Randomized trial of an adherence programme for clients with HIV.
AB  - Our aim was to determine if a comprehensive adherence package improved self
      reported adherence to antiretroviral therapy. The adherence package included an
      education programme, individualized planning of regimens, and the opportunity for
      a patient to choose from a number of adherence aids and reminder devices. A
      randomized step wedge design was used. Forty-three individuals were randomized to
      begin the intervention over a five-month period. There was a substantial fall in
      the number of missed doses reported for the last four days (0.76 to 0.38, P
      =0.03) and last seven days (1.5 to 0.74, P =0.005) but not for the last 28 days
      (2.5 to 2.5, P =0.63). There was no statistical difference in the viral load or
      CD4 lymphocyte count in the period before or after the intervention. The Morisky
      score during the pre and post intervention periods was significantly different (P
      =0.006), 2.9 (SD 0.9) and 3.3 (SD 0.8) respectively. This adherence package
      improved self reported adherence during the last four and seven days.

PMID- 14678588
TI  - The emergence of AIDS in Guatemala: inpatient experience at the Hospital General
      San Juan de Dios.
AB  - Little is known about the effect of human immunodeficiency virus (HIV) infection
      on the Central American healthcare system. We describe HIV-related admissions in
      a Guatemalan medical service. The study was conducted at Guatemala City's largest
      public hospital. Data were derived from standardized data collection sheets
      maintained by the HIV testing service and by HIV clinic physicians. Data were
      collected for 295 medicine admissions of 257 HIV-infected adults during an 18
      month period in 1999 and 2000; 30% of the patients were women. Average age was 33
      years. Only 12.5% of the patients had been diagnosed with HIV infection prior to
      1999 and nearly all had symptomatic AIDS. 60.3% of the patients were diagnosed
      with HIV infection during their hospitalization. The most common discharge
      diagnoses were tuberculosis (13.9%), toxoplasmosis, diarrhoea, candida and other
      fungal infections, and meningitis. Mean length of stay for HIV-positive patients
      was 17 days. 23.7% of the patients died during their hospitalization; this was
      double the mortality of non-HIV patients. HIV-infected patients represented 5.8%
      of the total admissions of the general medical wards. In a country where HIV
      prevalence is thought to be less than 1%, AIDS is now responsible for over 5% of
      admissions to a large medical service at a cost of $500,000 per year. These
      findings underline the importance of HIV infection in Central America and
      demonstrate the utility of tracking hospital admission data as a method of
      surveillance.

PMID- 14678589
TI  - Risk factors for HIV infection among women in Carletonville, South Africa:
      migration, demography and sexually transmitted diseases.
AB  - We investigate the prevalence of, and risk factors for, HIV infection among women
      in an urban South African setting. A random sample of 834 women was recruited
      into a community-based cross-sectional study. HIV prevalence was 37.1% with
      higher prevalence among migrant women (46.0%) than non-migrant women (34.7%),
      (odds ratio [OR]=1.61, 95% confidence interval [CI]: 1.11-2.31). The highest HIV
      prevalence (50.9%) was between ages 26 and 35 years. Having two or more lifetime
      partners increased the risk of HIV infection (OR=4.88, 95% CI: 3.01-7.89).
      Migration, age, marital status, alcohol use, syphilis and gonorrhoea were
      independently associated with HIV infection. Migration increases the risk of HIV
      infection. Provision of services to treat sexually transmitted diseases and
      educational empowerment programmes that will promote safer sex among migrant
      women are urgently needed.

PMID- 14678590
TI  - Factors associated with vertical HIV transmission during two different time
      periods: the impact of zidovudine use on clinical practice at a Brazilian
      reference centre.
AB  - Vertical HIV transmission rates and associated factors among mother-infant pairs
      cared for at a Brazilian reference centre from 1988 to 1993 (period 1), and from
      1996 to 1999 (period 2) were evaluated. A total of 150 and 239 infants born to
      HIV+ mothers were enrolled at birth during these periods. No zidovudine
      prophylaxis was available in period 1. In period 2, 92.4% of the infants were
      exposed to zidovudine (54% started at delivery or in the post-natal period).
      During period 1, 25 of 129 infants were found to be infected (19.4%; 95%
      confidence interval [CI]=13-27) vs 20 of 232 (8.6%; 95% CI=5-13) during period 2
      (P <0.01). After controlling for co-variables, this decline was due to zidovudine
      prophylaxis, either with complete (odds ratio [OR]=0.24; 95% CI=0.08-0.70) or
      incomplete (OR=0.37; 95% CI=0.17-0.81) regimens. Premature rupture of membranes
      (OR =3.2) and rhesus-negative blood type of the infant (OR=2.6) facilitated
      transmission. Although confirming the protective effect of zidovudine
      prophylaxis, alternative approaches aimed at pregnant women identified late are
      needed for this population.

PMID- 14678591
TI  - Human immunodeficiency virus in plasma and cervicovaginal secretions in Filipino
      women.
AB  - This study examined 30 HIV-infected women in Manila to assess the relationship
      between cervicovaginal and plasma HIV-1 viral load. An interview and gynaecologic
      examination was conducted and cervicovaginal lavage (CVL) and venous blood
      specimens were collected. HIV-1 RNA was detected in plasma samples of 24 patients
      (80%) and in CVL samples of 18 women (60%); 16 patients (53%) had detectable
      levels in both. CVL HIV-1 RNA was detectable in 75% of women (6/8) with plasma
      viral loads between 10,000 and 100,000 copies/mL and in 77% of women (10/13) with
      plasma viral loads higher than 100,000 copies/mL (P =0.0086). Among women with
      CD4 cell counts of less than 200, 200-500, and greater than 500/mm(3), CVL HIV-1
      RNA was detected in 73%, 69%, and 17% of women, respectively (P =0.1428). HIV-1
      RNA shedding in the genital tract was significantly associated with plasma viral
      load.

PMID- 14678592
TI  - 'You can't tell by looking': pilot study of a community-based intervention to
      detect asymptomatic sexually transmitted infections.
AB  - Innovative and non-stigmatizing interventions are required to reduce ethnic
      inequalities in rates of sexually transmitted infections among young people. We
      therefore designed an intervention, 'You can't tell by looking,' which combined
      health promotion with testing for gonorrhoea and chlamydia using nucleic acid
      amplification technology and treatment and partner notification delivered in the
      non-clinical settings. One hundred and eighty-one participants were seen in 13
      sessions in local further education colleges. Forty-three percent of participants
      were from Black Caribbean or Black Other ethnic groups and 39% were Black
      African: 125 of 181 participants were sexually active and 109 of these (87%)
      provided a urine specimen. 10/109 (9.2%, 95% confidence interval 4.5-16.2%)
      samples were confirmed positive for Chlamydia trachomatis and two were also
      positive for Neisseria gonorrhoeae. Only 7% of those tested found it
      embarrassing. The intervention was both feasible and acceptable to young people.
      It could be tested in a wider variety of non-clinical settings and evaluated in a
      cluster randomized trial.

PMID- 14678593
TI  - Awareness of HIV/AIDS and household environment of pregnant women in Pune, India.
AB  - Our objective was to determine the level of HIV/AIDS knowledge of pregnant women
      in India. In a sub-sample of these women, we documented the extent to which they
      experienced adverse social and physical difficulties within their home. The study
      was performed at an urban antenatal hospital clinic in Maharastra, India. From
      April to September 2001, structured interviews were conducted on 707 randomly
      selected antenatal clinic patients related to HIV/AIDS knowledge. Of these, 283
      were further interviewed to document any social or physical difficulties they
      experienced. Over 75% of women displayed knowledge of primary transmission
      routes. Nearly 70% of women demonstrated knowledge of maternal to child
      transmission, however, only 8% knew of any methods of prevention. TV and written
      material were more strongly related to knowledge than access to radio messages or
      conversations with individuals. Thirty per cent of the women experienced physical
      or mental abuse or their spouse's alcohol and/or drug problems. Women reporting
      such abuse were more than twice as likely to have adequate HIV/AIDS knowledge
      compared with women reporting no such abuse. We found no relationship between
      reported household abuse and educational level of woman, husband, occupation of
      either partner, language or religion. We found no relationship between HIV status
      and knowledge of HIV and no relationship between HIV status and risk of abuse in
      the household. However, the total number of HIV patients in our sample was very
      small.

PMID- 14678594
TI  - Cervical human papillomavirus infections in commercial sex workers-risk factors
      and behaviours.
AB  - We have investigated the prevalence of, and risk factors for, cervical human
      papillomavirus (HPV) infection in commercial sex workers (CSWs) and controls
      attending the same sexual health clinics in Sydney. A self-administered 'risk
      factor' questionnaire was completed and a Pap smear and a specimen for HPV
      detection and typing were taken. Results from the 288 CSWs and 266 controls were
      assessed by univariate and multivariate analyses. No significant difference in
      the rates of cervical HPV infection in CSWs (31.6%) and controls (24.4%) was
      found but HPV related cytological abnormalities were more common on the CSWs (P
      <0.05). In both groups, factors independently associated with HPV infection were
      the use of non-barrier contraception, cytological abnormalities, age under 36 and
      the number of non-paying sexual partners. A risk factor for CSWs only was sex
      work in Japan. A detailed 'work' history from CSWs may be useful to identify
      unsafe practices or work in countries where safer sex may be less acceptable.

PMID- 14678595
TI  - Prevalence and risk factors of STDs in rural Haiti: implications for policy and
      programming in resource-poor settings.
AB  - The goals of the current study are to: (1) estimate the prevalence of sexually
      transmitted diseases (STDs) among women accessing services at a women's health
      clinic in rural Haiti; and (2) identify risk factors for STDs in this setting.
      The design is a case control study, comparing risk factors for women who
      demonstrated positive laboratory results for chlamydia and/or gonorrhoea to women
      who tested negative for both of these pathogens. The strongest risk factors for
      chlamydia and/or gonorrhoea were largely economic variables, with work as a
      domestic servant increasing the risk by four-fold. Working as a market vendor
      reduced a woman's risk of having an STD by approximately 45%. Given that economic
      factors are strongly associated with STD risk in this context, one potential
      mechanism for reducing the risk of STDs, including HIV, would involve increasing
      economic opportunities for women in rural Haiti.

PMID- 14678596
TI  - Audit of HIV partner notification in a district general hospital.
AB  - We evaluated partner notification for HIV in a district general hospital over a
      two-year period. The majority of current partners were notified and 60% were
      found to be HIV-positive. No previous partners were successfully notified. We
      make recommendations intended to improve the rate of notification and testing.

PMID- 14678597
TI  - Assessing the role of anal intercourse in the epidemiology of AIDS in Africa.

PMID- 14678600
TI  - Distribution of CCR5-CCR2 haplotypes in an Argentinean population.

PMID- 14678601
TI  - Development of a cell-based enzyme-linked immunosorbent assay for high-throughput
      screening of HIV type 1 entry inhibitors targeting the coreceptor CXCR4.
AB  - CXCR4, a coreceptor for human immunodeficiency virus type 1 (HIV-1) X4 virus,
      plays an important role in virus entry into the target cells. Antiviral agents
      that bind to CXCR4 are expected to inhibit HIV-1 entry. A cell-based enzyme
      linked immunosorbent assay (ELISA) was developed utilizing an anti-CXCR4
      monoclonal antibody, 12G5, and cells expressing CD4 and CXCR4, U373-MAGI
      CXCR4(CEM) cells. Using this assay, we demonstrated that 12G5 specifically binds
      to the CXCR4-expressing cells, but not to CCR5-expressing cells and cells without
      CXCR4 and CCR5, consistent with the results obtained by using flow cytometry. The
      well-characterized CXCR4 antagonists, T22, T14012 (a downsized analog of T-22),
      and AMD3100, effectively inhibited 12G5 binding to CXCR4-expressing cells, while
      HIV-1 entry inhibitors targeting CD4 and gp41 as well as HIV-1 reverse
      transcriptase and protease inhibitors did not block the binding of 12G5 to U373
      MAGI-CXCR4(CEM) cells. The prepared plates containing the fixed cells could be
      stored at -80 degrees C for at least 5 months without affecting the cell
      reactivity with 12G5, which enhances the convenience of this method. This
      suggests that the cell-based ELISA is specific, sensitive, convenient, rapid, and
      economic. With a robotic sample processing system, this assay can be used for
      high-throughput screening of HIV-1 entry inhibitors targeted to the HIV-1
      coreceptor CXCR4.

PMID- 14678602
TI  - Assessing human alloimmunization as a strategy for inducing HIV type 1
      neutralizing anti-HLA responses.
AB  - Xenovaccination of rhesus macaques with human HLA Class I and II proteins has
      been demonstrated to elicit protective immunity against challenge with SIV grown
      in human cells. To determine if alloimmunization in humans could lead to
      protective immunity against HIV-1, we prospectively followed a small group of
      women receiving whole-cell alloimmunization in the form of leukocyte
      immunotherapy for recurrent spontaneous abortion. Whole-cell vaccine recipients
      and their respective partners (referred to as donors) provided pre- and
      postimmune blood samples for analysis. Study participants were HLA typed by
      sequence-specific PCR and antibodies specific for HLA Class I and II antigens
      were measured in recipient plasma. To determine if anti-HLA antibody responses
      detected in recipient plasma samples were capable of neutralizing HIV-1 in vitro,
      we grew laboratory strain HIV-1(IIIB) and primary isolate HIV-1(301660) in donor
      derived CD4(+) T lymphocytes. The ability of purified whole IgG from responding
      patients to neutralizing infectivity of the respective donor-derived virus was
      then assayed in vitro. All donor-recipient pairs were determined to be HLA
      discordant for at least one Class I and one Class II locus. Two of seven female
      recipients in total made strong anti-HLA antibody responses specific to the HLA
      haplotype of the male donor in response to the alloimmunization regimen. For one
      recipient, IgG antibodies specific for donor HLA Class I and II antigens were
      able to neutralize both HIV-1(IIIB) and a primary isolate HIV-1(301660). In
      addition polyclonal anti-HLA class II antibodies against a single determinant
      (DR4) of this donor were also neutralizing. In contrast, the other recipient
      exhibiting antibodies only against donor HLA Class I antigens did not neutralize
      HIV-1(IIIB). Using samples from a small number of women undergoing leukocyte
      immunotherapy, we have demonstrated for the first time that allele-specific anti
      HLA antibodies elicited through human alloimmunization are capable of
      neutralizing HIV-1 in vitro.

PMID- 14678603
TI  - A 6-base pair insertion in the protease gene of HIV type 1 detected in a protease
      inhibitor-naive patient is not associated with indinavir treatment failure.
AB  - Insertions in the protease gene of HIV-1 were rarely found and are not associated
      with reduced effectiveness of protease inhibitors although they are thought to be
      selected by protease inhibitor therapy. This is the first report of a 6-basepair
      insertion in the protease gene prior to protease inhibitor therapy.

PMID- 14678604
TI  - The hydrophobic internal region of bovine prion protein shares structural and
      functional properties with HIV type 1 fusion peptide.
AB  - The conserved fusion peptide at the N-terminus of HIV-1 envelope glycoprotein
      gp41 is involved in the virus-cell fusion reaction and in the cytopathic effects
      promoted by expression in single cells. The conserved bovine prion protein
      121KHVAGAAAAGAVVGGLGGYMLGSAMSR147 transmembrane region (BPrP(tm)) contains a
      sequence rich in Gly residues [i.e., 130GAVVGGLGGYMLGSAMSR147 (BPrP(mi))] that
      shows homology with HIV-1 fusion peptide. As in the case of the latter peptide,
      analysis of the BPrP(mi) interfacial hydrophobicity confirms that this stretch
      bears an intrinsic tendency to partitioning from the aqueous phase into
      membranes. Experimental analyses of BPrP(mi)-lipid interactions suggest several
      similarities between this sequence and HIV-1 fusion peptide. Infrared
      spectroscopy reveals a conformational plasticity of the membrane-associated prion
      sequence comparable to that displayed by the viral sequence. The adoption of a
      mainly alpha-helical structure correlates with the formation of lytic pores. This
      helical structure can be converted into a beta-sheet conformation by addition of
      calcium, a process that is accompanied by vesicle membrane fusion. In contrast,
      transmembrane BPrP(tm) associates with membranes in a nonlytic, mainly helical
      structure but also containing some random coil. Upon addition of calcium, the
      random coils disappear while the helical conformation remains. In the absence of
      membranes both prion and HIV-1 sequences form amyloid-type fibers. It is proposed
      that during the pathological processes induced by secreted PrPSc and its
      proteolytic fragments, conformational polymorphism displayed by membrane-inserted
      BPrP(mi) may play a role at perturbing the general architecture of the membrane
      lipid bilayer and inducing protein-protein aggregation at membrane surfaces.
      These findings suggest the existence of common mechanisms underlying cytotoxicity
      by PrP and HIV-1 gp41.

PMID- 14678605
TI  - Near full-length genomes of 15 HIV type 1 group O isolates.
AB  - Human immunodeficiency virus type 1 (HIV-1) is classified into three distinct
      groups; M (major), N (non-M/non-O), and O (outlier). Group M strains are further
      subclassified into subtypes, subsubtypes, and circulating recombinant forms
      (CRF). While the level of genetic diversity within group O is similar to that
      between group M subtypes, group O has not been classified into subtypes. A
      previous study, based on the phylogenetic analyses of the gag p24, pol p32, and
      env gp160 sequences from 39 group O isolates, laid the foundation for the
      classification of group O subtypes. Five phylogenetic clusters, I-V, were
      identified that have characteristics analogous to group M subtypes. However, a
      complete phylogenetic analysis and classification of group O requires the
      availability of at least two full-length and one partial genomes for each group O
      phylogenetic cluster. In this study, 15 group O isolates were selected for full
      genome sequencing. Phylogenetic analysis of the 15 sequences with eight
      additional group O genomes supports the classification of three group O subtypes
      (I-III) and the potential existence of one CRF (IV) and at least one additional
      subtype (V). The group O subtypes are equidistant to each other and lack
      subsegments of other subtypes. The intra- and intersubtype genetic distances for
      group O are similar in magnitude to the corresponding distances for group M
      subtypes. Intersubtype recombination was identified in three of the 23 (13%)
      group O genomes. Formal classification of group O subtypes should be forthcoming
      pending the analysis of additional group O genomes and agreement of the HIV
      nomenclature committee.

PMID- 14678606
TI  - Limited transmission of drug-resistant HIV type 1 in 100 Swedish newly detected
      and drug-naive patients infected with subtypes A, B, C, D, G, U, and CRF01_AE.
AB  - The prevalence of genetic drug resistance in newly diagnosed HIV-1 cases and
      potential subtype-specific mutation patterns were studied. Samples from 100 newly
      diagnosed patients were randomly chosen from three HIV clinics in Sweden,
      prospectively collected during the period June 1998 to August 2001. Viral RNA was
      extracted from plasma and an approximately 2000-bp fragment covering the protease
      (PR) and reverse transcriptase (RT) genes was sequenced. Subtypes A, B, C, D, G,
      U, and CRF01_AE were found. All 100 sequences had mutations reported to be
      involved in some drug resistance, revealing naturally occurring subtype-specific
      amino acid patterns. Such patterns may be important to consider when treating
      patients infected with nonsubtype B viruses. While many drug resistance mutations
      seem to be naturally occurring, 9% of the newly detected patients in Sweden may
      have been infected with virus from antiviral-treated patients. Among the
      individuals infected with resistant virus, the majority were infected with
      subtype B virus and belonged to the homosexual risk group. It may be important to
      routinely test for resistance in newly infected cases to improve the choice of
      drugs for treatment because the virus may revert and resistant forms can become
      latent.

PMID- 14678608
TI  - Primary infection of a male plasma donor with divergent HIV variants from the
      same source followed by rapid fluctuations in their relative frequency and viral
      recombination.
AB  - The replication of two HIV-1 variants (>4.0% divergent in the env gene) was
      observed during primary infection of a frequent plasma donor. Phylogenetic
      analysis indicated that both HIV-1 variants likely originated from the same
      source. Heteroduplex tracking analysis of the env V3-V5 region indicated that one
      of these variant emerged in the plasma at the time of seroconversion, 15 days
      after the initial detection of HIV-1 RNA. Sequencing of the entire protein-coding
      region of plasma viruses from Days 2, 22, and 31 showed possible regions of
      recombination in the pol locus occurring within the first month of infection. The
      very rapid fluctuations of HIV-1 variant frequencies and their recombination
      during primary infection may reflect changes in their relative fitness in the
      face of developing immunological responses.

PMID- 14678607
TI  - Recombination of HIV type 1C (C'/C") in Ethiopia: possible link of EthHIV-1C' to
      subtype C sequences from the high-prevalence epidemics in India and Southern
      Africa.
AB  - The magnitude and complexity of the HIV-1 genetic diversity are major challenges
      for vaccine development. Investigation of the genotypes circulating in areas of
      high incidence, as well as their interactions, will be a milestone in the
      development of an efficacious vaccine. Because HIV-1 subtype C (HIV-1C) is
      responsible for most of the 36 million infections worldwide we investigated the
      HIV-1C strains circulating in Ethiopia in a retrospective, cross-sectional study.
      Serum samples from HIV-1-positive individuals were collected in seven Ethiopian
      cities and towns. Nucleotide sequences of the gag, pol, and env genes were
      analyzed. We performed phylogenetic analysis by the neighbor-joining and maximum
      likelihood methods with sequences from 30 isolates, and we determined
      recombination by the bootscanning method as implemented in the SIMPLOT program.
      Sequence analyses of a 2600-nucleotide fragment (including the gag gene, the
      protease, and the 5' half of reverse transcriptase of the pol gene) and the
      corresponding V1V2/C2V3 envelope regions confirmed that two distinct HIV-1C
      genotypes (C' and C") are cocirculating in Ethiopia, as shown previously by the
      analysis of the C2V3 envelope region. We have identified intrasubtype
      recombination between the two HIV-1C genotypes, C' and C", with 6 of the 30 (20%)
      analyzed viruses being recombinants. The C' sequences were phylogenetically
      linked to the fast spreading viruses in India and southern Africa. Furthermore,
      all the recombinant viruses shared the C' V1V3 region of the envelope, suggesting
      that the prevalence of viruses with the C' envelope is increasing compared to the
      C" envelope. The possibility that viruses with a C' envelope have a biological
      advantage over the viruses with a C" envelope should be further investigated in
      biological and epidemiological studies.

PMID- 14678609
TI  - T cell responses in HIV type 1-infected adolescent minorities share similar
      epitope specificities with whites despite significant differences in HLA class I
      alleles.
AB  - African-Americans (AFAM) and Hispanics (HIS) represent only 13% and 12% of the
      U.S. population but 54% and 19%, respectively, of annually incident HIV-1
      infections in the United States. The 88 patients in the current study were from
      U.S. racial or ethnic minority groups (72% African-American, 17% Hispanic),
      female (85%), and adolescent (mean age 20 years). Their HLA allele distributions
      were distinct from patterns in U.S. whites. Overall, HIV-1-specific T cell
      responses were observed in 91% of participants: 75% recognized peptides in Gag,
      67% Pol, 57% Nef, and 41% Env. The patients recognized 87 (36%) of 244 Gag, Pol,
      Env, or Nef peptides tested. Similar to what has been seen in white cohorts,
      epitope-rich peptide clusters were identified within conserved functional domains
      in Gag matrix, Gag capsid, Pol reverse transcriptase, and Nef. Peptides
      representing variable regions from within the B subtype or with more changes from
      the B subtype consensus sequence were less likely to stimulate a positive T cell
      response. A small percentage (17%) of unique T cell responses was found in this
      cohort that displayed no previously known T cell epitopes. Dominant responses
      generally overlapped with epitope-rich regions in HIV-1 described previously for
      whites, although many of these peptides were likely restricted by HLA class I
      alleles not previously associated with these epitopes. Hence host genetic
      variation among different racial groups may have less impact on the utility of
      candidate HIV-1 vaccines than previously suspected.

PMID- 14678610
TI  - Short communication: reversible mitochondrial respiratory chain impairment during
      symptomatic hyperlactatemia associated with antiretroviral therapy.
AB  - Direct evidence confirming the hypothesis that a dysfunction of the mitochondrial
      respiratory chain (MRC) underlies the pathogenesis of hyperlactatemia associated
      with highly active antiretroviral therapy (HAART) is scarce. We studied
      mitochondrial DNA (mtDNA) content and MRC function in the skeletal muscle of an
      HIV-infected patient during an episode of symptomatic hyperlactatemia. Skeletal
      muscle biopsy was performed during the episode when the patient was symptomatic
      and 3 months later when the patient was clinically recovered. Assessment of
      mitochondria was performed using histological, polarographic,
      spectrophotometrical, and Southern blot and real time PCR DNA quantification
      methods. The histological study disclosed extensive mitochondrial impairment in
      the form of ragged-red fibers or equivalents on oxidative reactions. These
      findings were associated with an increase in mitochondrial content and a decrease
      in both mitochondrial respiratory capacity and MRC enzyme activities.
      Mitochondrial DNA content declined to 53% of control values. Mitochondrial
      abnormalities had almost disappeared later when the patient became asymptomatic.
      Our findings support the hypothesis that MRC dysfunction stands at the basis of
      HAART-related hyperlactatemia.

PMID- 14678611
TI  - To leave or to stay?: Battered women's concern for vulnerable pets.
AB  - Consistent with previous research, almost half of a sample of 41 pet-owning
      battered women reported that their partners had threatened or actually harmed
      their pets, and over a fourth reported that concern for their pets had affected
      their decisions about leaving or staying with the batterer. Differences between
      rural and urban women were not significant, although higher proportions of rural
      than urban women reported that their partners had threatened or harmed their pets
      and that concern for their pets had affected their decisions. For the sample as a
      whole, logistic regression analyses showed that women whose pets had been
      threatened or harmed were significantly more likely to report that concern for
      their pets had affected their decisions about leaving or staying. The findings
      suggest that service providers should inquire about battered women's concern for
      their pets and should include arrangements for animals in safety planning.

PMID- 14678612
TI  - The role of the bar context and social behaviors on women's risk for aggression.
AB  - The present study is an initial examination of the extent to which the
      environmental characteristics of bars and social behaviors that women engage in
      when drinking in this setting are associated with bar-related aggression. As
      expected, several environmental characteristics (e.g., young patrons, pool
      playing) and social behaviors (e.g., alcohol consumption, leaving the bar with
      strangers) were associated with more severe bar-related aggression experienced by
      women during the past year. These results shed light on the significant problem
      of bar-related aggression against women and can potentially be used to develop
      prevention and educational programs.

PMID- 14678613
TI  - Assessing allegations of domestic violence in child custody evaluations.
AB  - There has been an increased focus on child custody evaluations involving domestic
      violence allegations with much criticism of evaluators' training, practices, and
      procedures. A national survey of 115 child custody evaluators (doctoral and
      master's level) was conducted to explore these criticisms. Findings revealed
      adequate training, multiple sources of data collection, and practices/procedures
      that closely adhere to child custody guidelines. However, robust, specialized
      domestic violence instruments, tests, and questionnaires were underutilized.
      Respondents indicated that findings supporting domestic violence allegations had
      a substantial impact on their subsequent recommendations. Results are discussed
      in terms of the importance of assessing domestic violence when conducting custody
      evaluations and the need for developing practice standards in this domain.
      Generally, results did not support common criticisms of custody evaluation
      practice.

PMID- 14678614
TI  - Contextualizing depression and physical functioning in battered women: adding
      vulnerability and resources to the analysis.
AB  - This investigation examined the relationships between physical, psychological,
      and sexual abuse along with vulnerability appraisals, positive and negative
      social relations, and socioeconomic resources on battered women's depression
      symptomatology and physical functioning. Women were recruited following an
      incident of partner violence that resulted in a police-report or the filing of a
      protection order. Participants were surveyed using a standardized questionnaire.
      Bivariate correlations and multiple regressions were used to examine the
      relationships between predictors as well as the cumulative and unique
      contributions of each variable set in explaining depression and physical
      functioning. Findings indicate that vulnerability appraisals, social relations,
      and socioeconomic resources significantly explain women's depression and physical
      functioning over and above the unique effect of specific types of partner
      violence. Given that women's physical and mental health are important aspects of
      assisting women with safety planning and violence cessation strategies,
      implications for assessment and interventions for battered women are discussed.

PMID- 14678615
TI  - Experiencing and witnessing familial aggression and their relationship to
      physically aggressive behaviors among Filipino adolescents.
AB  - The effects of family violence on children's aggressive behaviors have been the
      focus of much research. However, results have been equivocal in at least the
      following three areas: (a) the specific effects on aggression of child-directed
      violence versus child-witnessed violence, (b) the salience of family violence as
      an explanation of aggression when other theoretically relevant explanations of
      aggression are controlled (i.e., peers, attachments, or moral beliefs), and (c)
      the gender-specific effects of family violence. Using a probability sample of
      adolescents from a medium-sized city in the Philippines, this article assesses
      the effects of child-directed and child-witnessed violence between parents on
      aggressive behaviors of adolescents while controlling for theoretically relevant
      explanations of aggression. Results show that child-witnessed and child-directed
      violence are positively and significantly related to self-reported aggression,
      that child-witnessed violence accounts for most of the variance in adolescent
      aggression, and that neither measures of family violence interacts with gender.

PMID- 14678616
TI  - Revictimization and self-harm in females who experienced childhood sexual abuse:
      results from a prospective study.
AB  - Lifetime trauma histories were ascertained for females with confirmed histories
      of childhood sexual abuse and comparison females participating in a longitudinal,
      prospective study. Abused participants reported twice as many subsequent rapes or
      sexual assaults (p = .07), 1.6 times as many physical affronts including domestic
      violence (p = .01), almost four times as many incidences of self-inflicted harm
      (p = .002), and more than 20% more subsequent, significant lifetime traumas (p =
      .04) than did comparison participants. Sexual revictimization was positively
      correlated with posttraumatic stress disorder symptoms (PTSD), peritraumatic
      dissociation, and sexual preoccupation. Physical revictimization was positively
      correlated with PTSD symptoms, pathological dissociation, and sexually permissive
      attitudes. Self-harm was positively correlated with both peritraumatic and
      pathological dissociation. Competing theoretical explanations for revictimization
      and self-harm are discussed and evaluated.

PMID- 14678618
TI  - The Western Journal of Nursing Research.

PMID- 14678617
TI  - Twenty-Five Years of the WJNR.

PMID- 14678619
TI  - Thank You, Dr. Pamela J. Brink.

PMID- 14678620
TI  - Memories of Being an Editor.

PMID- 14678621
TI  - WJNR from Genesis to Maturity.

PMID- 14678623
TI  - How Did We Get so Old so Soon?

PMID- 14678622
TI  - Remembering when. Sage Publications Acquired WJNR and the Aftermath.

PMID- 14678624
TI  - WJNR Researchmanship Revisited.

PMID- 14678625
TI  - How Time Flies: Strategies for Teaching Nursing Research.

PMID- 14678626
TI  - WJNR History of Nursing: Informatics Department.

PMID- 14678627
TI  - New Challenges for Issues in Clinical Nursing Research.

PMID- 14678628
TI  - Midwest Nursing Research Society News.

PMID- 14678629
TI  - Leishmania/HIV co-infections: epidemiology in Europe.
AB  - As the AIDS pandemic spreads to rural areas and human visceral leishmaniasis (VL)
      becomes more common in suburban areas, there is an ever greater degree of overlap
      between the geographical distributions of the two diseases and, in consequence,
      an increasing incidence of Leishmania/HIV co-infection. Cases of the co-infection
      have been reported from 35 countries around the world but most have been recorded
      in south-western Europe. There has been a total of 1911 cases detected in Spain,
      France, Italy and Portugal. The incidence of Leishmania/HIV co-infection is
      expected to continue increasing in eastern Africa but to fall in south-western
      Europe as increasing numbers of HIV-positives in the latter region are given the
      new, highly active, antiretroviral therapy (HAART). In 1998, a world-wide network
      of surveillance for the co-infection, which now includes 28 member institutions,
      was established by the World Health Organization (WHO) and the Joint United
      Nations Programme on HIV/AIDS (UNAIDS). In south-western Europe, the surveillance
      system is based on 16 institutions and is already well established. The
      systematic use of standardized and recently computerized case-report forms, a
      central international registry at the WHO's headquarters in Geneva, and the use
      of a geographical information system (GIS) for mapping and monitoring the co
      infections have together improved the overall quality of the epidemiological data
      gathering. All member institutions of the global network report to the WHO on an
      annual basis. The data collected are then analysed and periodically disseminated
      through international publications. The GIS allows the relevant epidemiological
      and demographic data-sets to be integrated and permits all detected cases of co
      infection to be mapped down to locality level. The system also allows the spatial
      distribution of cases to be visualised and analysed and the geographical spread
      of the co-infection to be monitored over time. The risk posed by co-infected
      patients, as a source of Leishmania infection for the sandflies feeding on them,
      has recently been confirmed. The parasites and HIV may also be transmitted as the
      result of needle-sharing among intravenous-drug users.

PMID- 14678630
TI  - Leishmania/HIV co-infection in Brazil: an appraisal.
AB  - Given the epidemiology of human leishmaniasis and AIDS in Brazil, numerous cases
      of Leishmania/HIV co-infection might be expected. Relatively few Brazilian cases
      have been reported, however, even from regions where the overall incidences of
      HIV and Leishmania infection are both relatively high. Many cases of co-infection
      probably go undetected because of a lack of awareness among clinicians or limited
      access to appropriate diagnostic methods. In contrast to the situation in Europe,
      intravenous-drug users do not predominate among those exposed to HIV infection in
      Brazil. The success of the Brazilian programme for the free and universal
      distribution of antiretroviral drugs has decreased the prevalences of the
      commoner opportunistic infections among HIV-positives and increased the longevity
      of AIDS cases. Recent changes in the epidemiological patterns of HIV and
      Leishmania infections are likely to lead to a greater degree of overlap and a
      greater risk of co-infection and they justify increased alertness. This review of
      the co-infection in Brazil addresses three main topics: the current situation, in
      terms of the epidemiology of AIDS and Leishmania infection; the related
      epidemiological trends and their likely impact on the co-infection; and the co
      infection cases reported in Brazil by June 2003.

PMID- 14678631
TI  - HIV and the transmission of Leishmania.
AB  - In many countries, Leishmania/HIV co-infection is now changing the epidemiology
      of visceral leishmaniasis. The levels of transmission of the parasites causing
      such leishmaniasis were previously dependent on the conventional zoonotic cycle,
      in which sandflies transmitted the parasites from infected canids to other canids
      or humans. The co-infection, however, has led not only to marked increases in the
      sandfly transmission of the parasites from immunodepressed individuals directly
      to other humans but also, probably, to artificial transmission between
      immunodepressed intravenous-drug users, as the result of needle sharing.

PMID- 14678632
TI  - Enzymatic polymorphism during Leishmania/HIV co-infection: a study of 381
      Leishmania strains received between 1986 and 2000 at the international cryobank
      in Montpellier, France.
AB  - Between 1986 and 2000, 381 Leishmania strains isolated from 288 HIV-positive
      patients were studied at the international cryobank in Montpellier, France. Most
      (95.1%) of the strains came from cases of visceral leishmaniasis but 4.9% were
      from HIV-positives with cutaneous leishmaniasis. The majority of the strains came
      from patients infected in the Mediterranean region, with a few originating in sub
      Saharan Africa and South America. Isoenzymatic characterization revealed 28
      zymodemes in four different species: L. infantum (which was predominant), L.
      donovani, L. major and L. guyanensis. The strains belonging to the L. infantum
      complex included 20 zymodemes, some of which have so far only been found in cases
      of Leishmania/HIV co-infection.

PMID- 14678633
TI  - Iso-enzymatic variability of Leishmania infantum in Spain.
AB  - In many areas of the Mediterranean basin, leishmaniasis can now be found in HIV
      positive individuals. Such cases of Leishmania/HIV co-infection are relatively
      common in southern Europe, Spain being the country that has reported the greatest
      number. Since 1984, 359 Spanish isolates of Leishmania infantum have been
      characterized at the Instituto de Salud Carlos III in Madrid. Most (94.6%) of the
      isolates came from HIV-positive patients. The results of iso-enzymatic analysis
      indicated a high level of variability among the isolates, the visceralization in
      HIV-positive individuals of variants considered to be dermotropic in the
      immunocompetent, and the appearance of new zymodemes among the HIV-positive human
      population.

PMID- 14678634
TI  - The identification and variability of the parasites causing leishmaniasis in HIV
      positive patients in Italy.
AB  - Between 1988 and 1998, 258 Leishmania strains from patients infected with HIV
      were characterized by iso-enzyme electrophoresis at the Istituto Superiore di
      Sanita (ISS) in Rome. Most (227) of the isolates came from 80 Italian patients
      with visceral leishmaniasis (VL), the rest from cases of Leishmania/HIV co
      infection in other Mediterranean countries. Every strain was found to be
      Leishmania infantum. In Italy, 19 zymodemes of L. infantum were identified,
      broadly divided into three groups. Over 50% of the Italian patients were infected
      by the commonest agent of Mediterranean VL in HIV-negative individuals (zymodeme
      MON-1) whereas the remaining patients were infected by two distinct groups of
      zymodemes: one usually causing simple, self-resolving cutaneous leishmaniasis in
      HIV-negative patients, the other consisting of agents detected, so far, only in
      HIV-positive subjects. This last group, consisting of seven zymodemes, showed re
      assortment patterns within electromorphs frequently observed in dermotropic L.
      infantum zymodemes. A similar grouping was also observed in the isolates from
      other Mediterranean countries. Basing on general data recorded at the ISS over
      the last 20 years, accurate identification of the geographical origin of the
      zymodemes was attempted by careful analysis of the patients' histories, using the
      iso-enzyme electromorphs as geographical markers. Furthermore, a polymorphism
      index (no. of zymodemes/no. of patients) was defined for each Leishmania species
      and geographical region, and used to assess the level of L. infantum zymodeme
      heterogeneity in Italy, before and after stratification by HIV status. The
      greatest zymodeme heterogeneity was found in Sicily (southern Italy), with nine
      zymodemes identified among only 30 HIV-positive patients.

PMID- 14678635
TI  - Lower trypanosomatids in HIV/AIDS patients.
AB  - Although the family Trypanosomatidae includes parasites of plants, insects and
      vertebrates, only two genera in the family, Leishmania and Trypanosoma, are
      usually found in humans. Since 1995, however, other monoxenous trypanosomatids
      have been isolated from several HIV-positive individuals, in whom the parasites
      cause either visceral or cutaneous lesions. These odd cases are reviewed here. It
      appears that immunocompromised patients may be vulnerable to infection with
      trypanosomatids (and other parasites) that either fail to survive or never cause
      detectable morbidity in the immunocompetent.

PMID- 14678636
TI  - The pathogenesis of Leishmania/HIV co-infection: cellular and immunological
      mechanisms.
AB  - The intracellular protozoan parasites of the genus Leishmania have been
      recognized as opportunistic pathogens in immunosuppressed individuals, including
      those infected with human immunodeficiency virus type-1 (HIV-1). Leishmaniasis
      and AIDS overlap in several sub-tropical and tropical regions around the world,
      including the Mediterranean area. In 1994, 3%-7% of HIV-1-infected individuals in
      southern Europe developed visceral leishmaniasis. In humans, interestingly, both
      HIV-1 and Leishmania interact with, invade, and multiply within cells of myeloid
      or lymphoid origin. The combined modulation of Leishmania - and HIV-1-related
      pathogenesis in the co-infected cases is therefore probably a realistic goal. In
      the light of the recent demonstration that L. donovani can up-regulate HIV-1
      replication, both in monocytoid and lymphoid cells in vitro and in co-infected
      individuals, it is clear from the epidemiological data available that Leishmania
      can probably act as a powerful co-factor in the pathogenesis of HIV-1 infection.
      In those who are co-infected, complex mechanisms involving cytokine secretion and
      cellular-signalling events play pivotal roles in the Leishmania-mediated
      activation and pathogenesis of HIV-1. An overview of the recent findings
      concerning this Leishmania/HIV-1 interaction is presented here.

PMID- 14678637
TI  - Visceral leishmaniasis in those infected with HIV: clinical aspects and other
      opportunistic infections.
AB  - Cases of visceral leishmaniasis (VL) in HIV-positive individuals have been
      reported from most areas of the world where the geographical distributions of the
      two infections overlap. The majority of the co-infected cases that have been
      recorded, however, live around the Mediterranean basin. In these subjects, the
      length of the incubation period of VL is presumably very short, particularly in
      those who have severe immunodepression. At diagnosis, almost all cases of VL/HIV
      co-infection have been found to have fewer than 200 CD4+ cells/microl blood, and
      about 50% meet the AIDS-defining criteria during their first episode of VL. The
      clinical manifestations of VL in HIV-infected individuals may be similar to those
      seen in HIV-negative cases; fever, pancytopenia and hepato-splenomegaly, for
      example, are found in 75% of all the HIV-positive cases. Following the
      dissemination of the parasites, however, the HIV-positive cases may develop
      unusual, multi-organ pathology. Almost all the cases of co-infection are very
      prone to VL relapses, even after carefully managed antileishmanial treatment. The
      opportunistic infections that are often seen in HIV-positives frequently develop
      during VL episodes, the signs and symptoms of the leishmaniasis then confusingly
      overlapping with those of the other infections.

PMID- 14678638
TI  - Leishmania and HIV co-infection: dermatological manifestations.
AB  - Leishmania species can cause a wide spectrum of cutaneous disease in HIV-positive
      patients: asymptomatic, localized cutaneous, mucosal, muco-cutaneous, diffuse
      cutaneous or post-kala-azar leishmaniasis. In such cases, which are usually
      severely immunocompromised, the leishmanial parasites reach the skin of the human
      host by dissemination after either a new infection (resulting from the bite of
      infected sandfly or, probably, the sharing of contaminated syringes by
      intravenous-drug users) or the re-activation of a latent infection. Recent
      experience and past observations on the dermatology of leishmaniasis in those
      with Leishmania/HIV co-infection are reviewed here.

PMID- 14678639
TI  - The biological diagnosis of leishmaniasis in HIV-infected patients.
AB  - This review emphasises the particular difficulties encountered in confirming a
      suspected case of cutaneous or visceral leishmaniasis when that case is co
      infected with HIV. HIV infection appears to have a more profound impact on the
      development of visceral leishmaniasis than on the evolution of the purely
      cutaneous disease. The various techniques available for immunological,
      parasitological and molecular diagnosis are presented and evaluated. The value of
      serodiagnosis for the detection of antileishmanial antibodies is in part
      dependent on the antigens used. Western blots may have a use not only in
      diagnosis but also in predicting the cases of HIV infection that are at most risk
      of developing symptomatic leishmaniasis. The presence of leishmanial parasites
      may still only be demonstrated incontrovertibly by the microscopical examination
      of smears or the culture of blood or biopsy samples. The use of cultures not only
      permits diagnosis but also detailed study of the parasites. The potential use of
      PCR in diagnosis is explored and related to other possible tests. A recommended,
      standardized procedure for the diagnosis of leishmaniasis in HIV-infected
      patients is presented.

PMID- 14678640
TI  - Treatment of leishmaniasis in HIV-positive patients.
AB  - Although, in southern Europe, there has been considerable experience in the
      treatment of visceral leishmaniasis (VL) in HIV-positive patients, the optimal
      therapy has yet to be established. Pentavalent antimony salts, free amphotericin
      B deoxycholate (ABD) and lipidic formulations of amphotericin B are the drugs
      most commonly used. Treatment with pentavalent antimonials requires daily
      injections for 28 days, is not well tolerated and leads to initial clinical cure
      in only 66% of the co-infected cases. Free ABD has to be given, intravenously,
      for just as long, has significant toxicity and leads to initial clinical cure in
      even fewer cases (62%). In a prospective, comparative trial, treatment of co
      infected cases with a pentavalent antimonial was found to have similar efficacy
      and toxicity to treatment with free ABD. The duration of treatment and the
      associated toxicity may both be reduced by the use of lipidic formulations of
      amphotericin B. Anecdotal evidence and the results of non-randomized trials
      indicate that treatment with liposomal amphotericin B is highly effective. In a
      comparative trial, amphotericin B lipid complex was found to be not only as
      effective as a pentavalent antimonial but also better tolerated. At the moment,
      however, such lipidic formulations have only been tested against VL/HIV cases in
      Europe, not elsewhere in the world, and they remain very expensive. However
      successful the treatment in terms of initial clinical cure, almost all VL/HIV
      cases develop VL relapses. Although the data available on secondary prophylaxis
      are limited and often inconclusive, it appears that regular treatment with a
      pentavalent antimonial drug, liposomal amphothericin B or amphotericin B lipid
      complex can reduce the incidence of leishmanial relapses in HIV-positive patients
      with VL. The development of new regimens, use of new oral drugs (such as
      miltefosine) and the development of new antileishmanial drugs could all improve
      the treatment of HIV-related VL in the future.

PMID- 14678641
TI  - The impact of highly active antiretroviral therapy (HAART) on visceral
      leishmaniasis in Spanish patients who are co-infected with HIV.
AB  - Clinicians in Madrid have been observing and treating HIV-positive patients with
      visceral leishmaniasis (VL) for over a decade. As their records cover some of the
      co-infection cases that occurred before and after highly active antiretroviral
      therapy (HAART) was introduced into Spain, retrospective analysis of the records
      has allowed some of the effects of HAART on local VL to be determined.
      Encouragingly, HAART appears to have decreased the annual incidence of VL among
      local AIDS cases, from 4.81 cases/100 to just 0.8 case/100 (P <0.0005), a first
      episode of VL now appearing only when there is obvious HAART failure.
      Unfortunately, it does not seem to be very good at preventing VL relapses; within
      24 months of antileishmanial treatment, 70% of patients who were receiving HAART
      had such relapses. The mean time between antileishmanial treatment and VL relapse
      was, however, longer when HAART was used than when it was not (20 v. 13 months).
      In those receiving HAART, relapses of the VL often occurred despite increasing
      CD4+ cell counts and undetectable HIV loads, indicating that successful treatment
      of the viral infection is insufficient to prevent the relapse of the
      leishmaniasis. These results are in general agreement with other observations
      made in Spain. VL relapses are possible and even frequent in HIV-positives who
      have no more than 200 CD4+ cells/microl, but secondary prophylaxis to prevent VL
      relapses may be safely suspended if a CD4+ count of >200 cells/microl can be
      maintained using HAART. VL also seems to hamper the immunological recovery of the
      HIV-positive, although HAART appears to have little effect on the clinical
      manifestations of VL.

PMID- 14678642
TI  - Clinical survey of Leishmania/HIV co-infection in Catania, Italy: the impact of
      highly active antiretroviral therapy (HAART).
AB  - The clinical and parasitological features of visceral leishmaniasis (VL) were
      investigated, retrospectively, in 27 HIV-infected patients who attended the out
      patient clinic of Catania University's Department of Infectious Diseases between
      1990 and 1998. The aim was to evaluate the epidemiological, clinical, therapeutic
      and prognostic characteristics of the co-infection, to determine if there were
      any interactions between the two infections, and to see if the use of highly
      active antiretroviral therapy (HAART) had any impact on the leishmaniasis. The
      most dramatic observation was a marked, HAART-attributable reduction in the
      annual incidence of VL relapses among the patients.

PMID- 14678644
TI  - Recombinant anti-botulinum neurotoxin A single-chain variable fragment antibody
      generated using a phage display system.
AB  - A recombinant single-chain fragment variable antibody (scFv) to botulinum A
      neurotoxin (BoNT/A) was developed. BALB/C mice were immunized with BoNT/A.
      Splenomic RNA was isolated from the hyperimmune mice and used to prepare a cDNA
      library, from which the variable regions of the heavy and light chain antibody
      genes were generated and connected by a DNA linker. The resulting scFv genes were
      cloned into the phagemid vector pCANTAB5 in order to construct phage display scFv
      libraries. Individual anti-BoNT/A phage clones were isolated from the phage
      display libraries by immunoaffinity selection using immobilized BoNT/A and
      further evaluated by enzyme-linked immunosorbant assay, immunoprecipitation and
      Western blotting. Forty-eight clones were found to be BoNT/A-reactive. The most
      reactive clone, designated D12, was selected for further study. The scFv gene of
      D12 was subcloned into a Pichia pastoris vector, and expression in yeast was
      evaluated.

PMID- 14678645
TI  - Generation of a monoclonal antibody to a cryptic site common to both integrin
      beta1 as well as gelatinase MMP9.
AB  - Integrins are one class of cell surface receptors that have been implicated in
      the regulation of a diverse set of cellular processes, including cell adhesion,
      migration, and invasion as well as gene expression, differentiation, and signal
      transduction. Cellular invasion not only requires the adhesive properties of
      integrins but also the proteolytic properties of matrix-degrading enzymes, such
      as the metalloproteinases (MMPs). Previous studies have shown that integrin
      alphavbeta3 is a receptor for MMP2, localizing its proteinase activity to the
      cell surface, ultimately leading to site-specific extracellular matrix (ECM)
      degradation. Here we develop reagents to investigate the possibility of an
      interplay between MMP9 and integrin alpha5beta1. With the use of EV22 viral
      studies, the tetrapeptide sequence, LRSG, was shown to be a dimerizing sequence
      mediating beta1 integrin binding to EV22. The same study also showed that
      cellular infection could be halted with the use of LRSG-containing peptides. In a
      later study, in an effort to isolate inhibitors of the MMP family, LRSG sequence
      was identified as one capable of binding MMP9. Interestingly, MMP9 contains an
      LRSG sequence, raising the possibility that MMP9 binds the cell surface via beta1
      integrins through the dimerizing LRSG motif. We used the LRSG-containing sequence
      from beta1 integrins as an antigen to generate the monoclonal antibody (MAB)
      FM155 in the mouse model. MAB FM155 will help identify a cryptic epitope, LRSG,
      and its role in matrix remodeling as well as tumor growth, cancer cell migration,
      and angiogenesis.

PMID- 14678646
TI  - New monoclonal antibodies to non-glycosylated domains of the secreted mucins
      MUC5B and MUC7.
AB  - The separation and characterization of salivary mucins is not straightforward
      because of their large size, heterogeneity, and molecular interactions. The MUC5B
      and MUC7 mucins are major glycoprotein components of saliva that are thought to
      play a vital role in maintaining oral health. MUC5B is also a major component of
      respiratory mucus and is produced by the tracheal and bronchial glands, while
      MUC7 has a more limited pattern of expression in the bronchial tree. MUC5B is a
      gel-forming mucin and thus confers viscosity, whereas MUC7 is much smaller. MUC7
      has anti-fungal activity, and both mucins interact with bacteria. The aim of this
      work was to produce new monoclonal antibodies that can be used to quantify and
      characterize these mucins by standard laboratory procedures. Peptide sequences in
      non-conserved and non-glycosylated regions were selected and monoclonal
      antibodies produced by an efficient immunization and cloning strategy, and
      screening against purified mucins. Three new antibodies-EU-MUC5Ba and EU-MUC5Bb
      (against MUC5B) and EU-MUC7a (against MUC7)-were isolated that do not show cross
      reactivity with other gel-forming mucins. All work on immunohistochemistry can be
      used for semi-quantitative immunoblotting after agarose gel electrophoresis.
      These reagents are valuable tools to study changes in these mucins in oral and
      respiratory disease, and unlike other monoclonal antibodies to these mucins they
      recognize epitopes that are not affected by glycosylation.

PMID- 14678647
TI  - Production and characterization of monoclonal antibodies with specificity for
      human HLA-G isoforms.
AB  - Production of monoclonal antibodies to HLA-G, a nonpolymorphic antigen of non
      classical HLA class I, is of basic and clinical importance. In the present study,
      monoclonal antibodies were prepared which recognize different membrane bound and
      soluble isoforms of HLA-G, following immunization of BALB/c mice with a synthetic
      peptide. Use of this peptide (23 residues), which is present in the alpha1 domain
      of HLA-G, was previously demonstrated to provide antibodies useful for
      recognition of HLA-G isoforms in human placenta. Antibody-producing hybridomas
      were screened by an indirect one-step ELISA method. A clone designated 5E6H7,
      secreted antibodies useful in immunostaining studies involving both surface HLA-G
      of placental tissues and soluble forms of this antigen in human sera. In
      addition, unreactivity of this antibody with human lymphocytes and sections of
      normal human skin was observed by immunofluorescence microscopy, thus
      demonstrating its specificity for HLA-G.

PMID- 14678648
TI  - Generation and characterization of an anti-idiotype monoclonal antibody related
      to GM3(NeuGc) ganglioside.
AB  - The 14F7 monoclonal antibody (MAb), IgG1 isotype, which reacts specifically to
      GM3(NeuGc) ganglioside induced a specific IgG anti-idiotypic antibody (Ab2)
      response in syngeneic mice when it was administered coupled with KLH and in the
      presence of Freund's adjuvant. Spleen cells from these mice were used in somatic
      cell hybridization experiments using the murine myeloma cell line P3-X63-Ag8 653
      as fusion partner. An IgG1 Ab2 MAb was selected. This Ab2 MAb, called 4G9, was
      able to block the binding of 14F7 MAb to GM3(NeuGc) ganglioside and developed a
      strong IgG anti-anti-idiotypic antibody (Ab3) response, when injected into
      syngeneic mice. These Ab3 antibodies were characterized to bear 14F7 MAb
      idiotopes, but did not have the same specificity as 14F7 MAb. In the other hand,
      a very specific anti-NeuGc-containing ganglioside response was generated in
      chickens immunized with this Ab2 MAb, thus behaving, in this species as an
      "internal image" antibody.

PMID- 14678649
TI  - Production and characterization of monoclonal antibodies to E1 Tor toxin co
      regulated pilus of Vibrio cholerae.
AB  - Murine monoclonal antibodies (MAbs) against Vibrio cholerae toxin co-regulated
      pilus (TCP) were generated using conventional hybridoma procedures. Four
      hybridomas were obtained and two characterized. Hybridomas 10E10E1 and 4D6F9
      secreted antibodies of the IgG2a and IgG1 isotypes, respectively, that reacted
      with a 24-kDa antigen corresponding to the product of the El Tor tcpA gene fused
      to a six Histidine tail. Additionally, MAbs produced by 4D6F9 selectively
      recognized the major pilin subunit (TcpA) of El Tor and O139 vibrios in western
      immunoblot, while MAbs from 10E10E1 also cross-reacted with classical TcpA.
      Furthermore, vibrios expressing TCP on their surface selectively inhibited
      binding of the antibodies secreted by both hybridomas to TcpA-coated microtiter
      plates. Thus, the MAbs reported in this work detected the structural subunit of
      the pilus either denatured or assembled on the bacterial surface.

PMID- 14678650
TI  - Mouse myeloma cell line Sp2/0 multidrug-resistant variant as parental cell line
      for hybridoma construction.
AB  - The use of multidrug-resistant variant of Sp2/0 mouse myeloma cell line SpEBr-5
      as a partner for making mouse hybridoma producing monoclonal antibodies is
      described here. The resulting hybridoma cell line 1F7 was characterized with a
      high level of monoclonal antibody production and karyotype containing all normal
      mouse chromosomes. 1F7 cells were separately selected for resistance to ethidium
      bromide (EBr) and adriamycin (ADR) and different mechanisms of drug resistance
      were found in these cell variants. The resistance in ADR-selected 1F7 cells was
      due to amplification and overexpression of mdr genes. In EBr-resistant 1F7 cells,
      mdr genes were overexpressed without amplification. Substantially decreased level
      of Topo II activity in both cell lines also suggests the existence of additional
      mechanisms for MDR phenotype of hybridoma cells. Finally, adriamycin-resistant
      1F7 hybridoma cell variant was found to produce higher level of specific
      immunoglobulins due to the increased level of Iggamma(2b) heavy chain mRNA.

PMID- 14678651
TI  - Development of mouse hybridomas by fusion of myeloma cells with lymphocytes
      derived from spleen, lymph node, and bone marrow.
AB  - Since its discovery by Kohler and Milstein in 1975, hybridoma technology has
      found a wide use in almost every field of biology and medicine. A general and
      simple approach for developing monoclonal antibodies is to use splenocytes from
      immunized mice. In the present study, 10 fusion experiments were carried out to
      analyze the hybridization efficiencies of mouse myeloma cells with lymphocytes
      derived from spleen, lymph node, and bone marrow and we found a higher yield of
      antigen specific antibody producing hybridoma lines when the lymph nodes were
      used.

PMID- 14678652
TI  - A functional anti-human 4-1BB ligand monoclonal antibody that enhances
      proliferation of monocytes by reverse signaling of 4-1BBL.
AB  - 4-1BB Ligand (4-1BBL), a transmembrane molecule, member of the tumor necrosis
      factor ligand superfamily, is an important costimulatory molecule in the immune
      response. In this study a functional anti-human 4-1BBL MAb 1F1 was obtained and
      the specificity of this MAb was verified by flow cytometry and Western blotting.
      This MAb effectively recognized the 4-1BBL molecule expressed on a series of
      malignant cell lines as well as on DC and monocytes and it inhibited the
      proliferation of T lymphocytes, costimulated by soluble 4-1BBL and agonist anti
      human CD3 MAb. Furthermore, we demonstrated that MAb 1F1 induced an impressive
      proliferation of monocytes from peripheral blood by triggering the reverse signal
      through 4-1BBL. This functional anti-human 4-1BBL MAb provides a valuable tool
      for further study of biological functions as well as signal transduction of 4
      1BBL/4-1BB.

PMID- 14678657
TI  - The NASA Astrobiology Institute: early history and organization.
AB  - The NASA Astrobiology Institute (NAI) was established as a means to advance the
      field of astrobiology by providing a multidisciplinary, multi-institution,
      science-directed program, executed by universities, research institutes, and NASA
      and other government laboratories. The scientific community and NASA defined the
      science content at several workshops as summarized in the NASA Astrobiology
      Roadmap. Teams were chosen nationwide, following the recommendations of external
      review groups, and the research program began in 1998. There are now 16 national
      Teams and five international affiliated and associated astrobiology institutions.
      The NAI has attracted an outstanding group of scientific groups and individuals.
      The Institute facilitates the involvement of the scientists in its scientific and
      management vision. Its goal is to support basic research and allow the scientists
      the freedom to select their projects and alter them as indicated by new research.
      Additional missions include the education of the public, the involvement of
      students who will be the astrobiologists of future generations, and the
      development of a culture of collaboration in NAI, a "virtual institute," spread
      across many sites nationally and internationally.

PMID- 14678658
TI  - Biosignatures of early earths.
AB  - A major goal of NASA's Origins Program is to find habitable planets around other
      stars and determine which might harbor life. Determining whether or not an
      extrasolar planet harbors life requires an understanding of what spectral
      features (i.e., biosignatures) might result from life's presence. Consideration
      of potential biosignatures has tended to focus on spectral features of gases in
      Earth's modern atmosphere, particularly ozone, the photolytic product of
      biogenically produced molecular oxygen. But life existed on Earth for about
      1(1/2) billion years before the buildup of atmospheric oxygen. Inferred
      characteristics of Earth's earliest biosphere and studies of modern microbial
      ecosystems that share some of those characteristics suggest that organosulfur
      compounds, particularly methanethiol (CH(3)SH, the sulfur analog of methanol),
      may have been biogenic products on early Earth. Similar production could take
      place on extrasolar Earth-like planets whose biota share functional chemical
      characteristics with Earth life. Since methanethiol and related organosulfur
      compounds (as well as carbon dioxide) absorb at wavelengths near or overlapping
      the 9.6-microm band of ozone, there is potential ambiguity in interpreting a
      feature around this wavelength in an extrasolar planet spectrum.

PMID- 14678659
TI  - Introduction to the special paper collection: methodologies and techniques for
      detecting extraterrestrial (microbial) life.

PMID- 14678661
TI  - Near-infrared detection of potential evidence for microscopic organisms on
      Europa.
AB  - The possibility of an ocean within the icy shell of Jupiter's moon Europa has
      established that world as a primary candidate in the search for extraterrestrial
      life within our Solar System. This paper evaluates the potential to detect
      evidence for microbial life by comparing laboratory studies of terrestrial
      microorganisms with measurements from the Galileo Near Infrared Imaging
      Spectrometer (NIMS). If the interior of Europa at one time harbored life, some
      evidence may remain in the surface materials. Examination of laboratory spectra
      of terrestrial extremophiles measured at cryogenic temperatures reveals
      distorted, asymmetric nearinfrared absorption features due to water of hydration.
      The band centers, widths, and shapes of these features closely match those
      observed in the Europa spectra. These features are strongest in reddish-brown,
      disrupted terrains such as linea and chaos regions. Narrow spectral features due
      to amide bonds in the microbe proteins provide a means of constraining the
      abundances of such materials using the NIMS data. The NIMS data of disrupted
      terrains exhibit distorted, asymmetric near-infrared absorption features
      consistent with the presence of water ice, sulfuric acid octahydrate, hydrated
      salts, and possibly as much as 0.2 mg cm(-3) of carbonaceous material that could
      be of biological origin. However, inherent noise in the observations and
      limitations of spectral sampling must be taken into account when discussing these
      findings.

PMID- 14678660
TI  - Terahertz circular dichroism spectroscopy: a potential approach to the in situ
      detection of life's metabolic and genetic machinery.
AB  - We propose a terahertz (far-infrared) circular dichroism-based life-detection
      technology that may provide a universal and unequivocal spectroscopic signature
      of living systems regardless of their genesis. We argue that, irrespective of the
      specifics of their chemistry, all life forms will employ well-structured, chiral,
      stereochemically pure macromolecules (>500 atoms) as the catalysts with which
      they perform their metabolic and replicative functions. We also argue that nearly
      all such macromolecules will absorb strongly at terahertz frequencies and exhibit
      significant circular dichroism, and that this circular dichroism unambiguously
      distinguishes biological from abiological materials. Lastly, we describe several
      approaches to the fabrication of a terahertz circular dichroism spectrometer and
      provide preliminary experimental indications of their feasibility. Because
      terahertz circular dichroism signals arise from the molecular machinery necessary
      to carry out life's metabolic and genetic processes, this life-detection method
      differs fundamentally from more well-established approaches based on the
      detection of isotopic fractionation, "signature" carbon compounds, disequilibria,
      or other by-products of metabolism. Moreover, terahertz circular dichroism
      spectroscopy detects this machinery in a manner that makes few, if any,
      assumptions as to its chemical nature or the processes that it performs.

PMID- 14678662
TI  - Possibilities for the detection of microbial life on extrasolar planets.
AB  - We consider possibilities for the remote detection of microbial life on
      extrasolar planets. The Darwin/Terrestrial Planet Finder (TPF) telescope concepts
      for observations of terrestrial planets focus on indirect searches for life
      through the detection of atmospheric gases related to life processes. Direct
      detection of extraterrestrial life may also be possible through well-designed
      searches for microbial life forms. Satellites in Earth orbit routinely monitor
      colonies of terrestrial algae in oceans and lakes by analysis of reflected ocean
      light in the visible region of the spectrum. These remote sensing techniques
      suggest strategies for extrasolar searches for signatures of chlorophylls and
      related photosynthetic compounds associated with life. However, identification of
      such life-related compounds on extrasolar planets would require observations
      through strong, interfering absorptions and scattering radiances from the remote
      atmospheres and landmasses. Techniques for removal of interfering radiances have
      been extensively developed for remote sensing from Earth orbit. Comparable
      techniques would have to be developed for extrasolar planet observations also,
      but doing so would be challenging for a remote planet. Darwin/TPF coronagraph
      concepts operating in the visible seem to be best suited for searches for
      extrasolar microbial life forms with instruments that can be projected for the
      2010-2020 decades, although resolution and signal-to-noise ratio constraints
      severely limit detection possibilities on terrestrial-type planets. The
      generation of telescopes with large apertures and extremely high spatial
      resolutions that will follow Darwin/TPF could offer striking possibilities for
      the direct detection of extrasolar microbial life.

PMID- 14678663
TI  - Microcolonial fungi: survival potential of terrestrial vegetative structures.
AB  - So far mainly spores or other "differentiated-for-survival" structures were
      considered to be resistant against extreme environmental constraints (including
      extraterrestrial challenges). Microcolonial fungi (MCF) are unique growth
      structures formed by eukaryotic microorganisms inhabiting rock varnish surfaces
      in terrestrial deserts. They are here proposed as a new object for exobiological
      study. Sun-exposed desert rocks provide surface habitats with intense solar
      radiation, a scarce water supply, drastic changes in temperature, and episodic to
      sporadic availability of nutrients. These challenging conditions reduce the
      diversity of life to MCF, whose resistance to desiccation and tolerance for
      ultraviolet (UV) radiation make them survival specialists. Based upon our studies
      of MCF, we propose that the following mechanisms are universally employed for
      survival on rock surfaces: (1) compact tissue-like colony organization formed by
      thermodynamically optimal round cells embedded in extracellular polymeric
      substances, (2) the presence of several types of UV-absorbing compounds (melanins
      and mycosporines) and antioxidants (carotenoids, melanins, and mycosporines) that
      convey multiple stress resistance to desiccation, temperature, and irradiation
      changes, and (3) intracellular developmental mechanisms typical for these
      structures.

PMID- 14678664
TI  - Finding extraterrestrial organisms living on thermosynthesis.
AB  - During thermal cycling, organisms could live on thermosynthesis, a theoretical
      mechanism applicable to the origin of life and the early evolution of biological
      energy conversion. All extraterrestrial ice may be a repository for frozen dead
      or dormant organisms from earlier stages of evolution. In the presence of a
      thermal gradient within the ice, organisms might still be harvesting energy from
      thermosynthesis. Possible habitats for thermosynthesizers can be found throughout
      the Solar System, particularly in the cold traps on Mercury and the Moon,
      convecting waters on Mars, the oceans on moons in the outer Solar System, and
      smaller bodies rotating in the sunlight such as cosmic dust, meteorites,
      asteroids, and comets. A general strategy for detecting thermosynthetic organisms
      on Earth is offered, and highlights of current and upcoming robotic exploratory
      missions relevant to the detection of thermosynthesis are reviewed.

PMID- 14678665
TI  - Why Raman spectroscopy on Mars?--a case of the right tool for the right job.
AB  - We provide a scientific rationale for the astrobiological investigation of Mars.
      We suggest that, given practical constraints, the most promising locations for
      the search for former life on Mars are palaeolake craters and the evaporite
      deposits that may reside within them. We suggest that Raman spectroscopy offers a
      promising tool for the detection of evidence of former (or extant) biota on Mars.
      In particular, we highlight the detection of hopanoids as long-lived bacterial
      cell wall products and photosynthetic pigments as the most promising targets. We
      further suggest that Raman spectroscopy as a fibre optic-based instrument lends
      itself to flexible planetary deployment.

PMID- 14678666
TI  - Evaporites, water, and life, part 1. Introduction.

PMID- 14678667
TI  - Supraglacial sulfur springs and associated biological activity in the Canadian
      high arctic-signs of life beneath the ice.
AB  - Unique springs, discharging from the surface of an arctic glacier, release H(2)S
      and deposit native sulfur, gypsum, and calcite. The presence of sulfur in three
      oxidation states indicates a complex series of redox reactions. Physical and
      chemical conditions of the spring water and surrounding environment, as well as
      mineralogical and isotopic signatures, suggest biologically mediated reactions.
      Cell counts and DNA analyses confirm bacteria are present in the spring system,
      and a limited number of sequenced isolates suggests that complex communities of
      bacteria live within the glacial system.

PMID- 14678668
TI  - Complex morphological variability in complex evaporitic systems: thermal spring
      snails from the Chihuahuan Desert, Mexico.
AB  - Thermal springs in evaporitic environments provide a unique biological laboratory
      in which to study natural selection and evolutionary diversification. These
      isolated systems may be an analogue for conditions in early Earth or Mars
      history. One modern example of such a system can be found in the Chihuahuan
      Desert of north-central Mexico. The Cuatro Cienegas basin hosts a series of
      thermal springs that form a complex of aquatic ecosystems under a range of
      environmental conditions. Using landmark-based morphometric techniques, we have
      quantified an unusually high level of morphological variability in the endemic
      gastropod Mexipyrgus from Cuatro Cienegas. The differentiation is seen both
      within and between hydrological systems. Our results suggest that this type of
      environmental system is capable of producing and maintaining a high level of
      morphological diversity on small spatial scales, and thus should be a target for
      future astrobiological research.

PMID- 14678669
TI  - Modern and ancient extremely acid saline deposits: terrestrial analogs for
      martian environments?
AB  - Extremely acid (pH <1) saline lakes and groundwaters existed in the mid-Permian
      of the mid-continent of North America. Modern counterparts have been found in
      acid saline lake systems throughout southern Australia. We compare and contrast
      the Permian Opeche Shale of North Dakota and Nippewalla Group of Kansas to modern
      Australian salt lakes in southern Western Australia and in northwest Victoria.
      With the exception of some minor variations in pH, evaporite mineralogy, and
      water geochemistry, the Permian and modern systems are similar and characterized
      by: (1) ephemeral saline continental playas hosted by red siliciclastic
      sediments, (2) evaporite minerals, including abundant sulfates, (3) Al-Fe-Si-rich
      waters with low pH values, (4) acidophilic microbes, and (5) paucity of
      carbonates. The composition of these terrestrial systems is strikingly similar to
      compositional data returned from the martian surface. Specifically, both Earth
      and martian systems have high amounts of iron oxides and sulfates, and little, if
      any, carbonates. We propose that the modern and ancient terrestrial acid saline
      environments may be good analogs for possible environments on Mars.

PMID- 14678670
TI  - Determination of epsomite-hexahydrite equilibria by the humidity-buffer technique
      at 0.1 MPa with implications for phase equilibria in the system MgSO4-H2O.
AB  - Epsomite (MgSO(4).7H(2)O) and hexahydrite (MgSO(4).6H(2)O) are common minerals
      found in marine evaporite deposits, in saline lakes as precipitates, in
      weathering zones of coal and metallic deposits, in some soils and their
      efflorescences, and possibly on the surface of Europa as evaporite deposits.
      Thermodynamic properties of these two minerals reported in the literature are in
      poor agreement. In this study, epsomite-hexahydrite equilibria were determined
      along four humidity-buffer curves at 0.1 MPa and between 25 and 45 degrees C.
      Results obtained for the reaction epsomite = hexahydrite + H(2)O, as demonstrated
      by very tight reversals along each humidity buffer, can be represented by ln K(+/
      0.012) = 20.001 - 7182.07/T, where K is the equilibrium constant, and T is
      temperature in Kelvin. The derived standard Gibbs free energy of reaction is
      10.13 +/- 0.07 kJ/mol, which is essentially the same value as that calculated
      from vapor pressure measurements reported in the literature. However, this value
      is at least 0.8 kJ/mol lower than those calculated from the data derived mostly
      from calorimetric measurements.

PMID- 14678671
TI  - Mollusc-microbe mutualisms extend the potential for life in hypersaline systems.
AB  - Metazoans in extreme environments have evolved mutualisms with microbes that
      extend the physical and chemical capabilities of both partners. Some of the best
      examples are bivalve molluscs in evaporite and hypersaline settings. Mollusc
      tissue is developmentally and evolutionarily amenable to housing vast numbers of
      symbiotic microbes. Documented benefits to the host are nutritional. Multiple
      postulated benefits to the microbes are related to optimizing metabolic
      performance at interfaces, where heterogeneity and steep gradients that cannot be
      negotiated by microbes can be spanned by larger metazoan hosts. A small cockle,
      Fragum erugatum, and its photosymbiotic microbes provide a remarkable example of
      a mutualistic partnership in the hypersaline reaches of Shark Bay, Western
      Australia. Lucinid bivalves and their endosymbiotic chemolithotrophic bacteria
      provide examples in which hosts span oxic/anoxic interfaces on behalf of their
      symbionts at sites of seafloor venting. Multiple lines of evidence underscore the
      antiquity of mutualisms and suggest that they may have played a significant role
      in life's first experiments above the prokaryotic grade of complexity. The study
      of metazoan-microbe mutualisms and their signatures in extreme environments in
      the geologic record will provide a significant augmentation to microbial models
      in paleobiology and astrobiology. There are strong potential links between
      mutualisms and the early history of life on Earth, the persistence of life in
      extreme environments at times of global crisis and mass extinction, and the
      possibilities for life elsewhere in the universe.

PMID- 14678674
TI  - Play.

PMID- 14678675
TI  - Social play and autistic spectrum disorders: a perspective on theory,
      implications and educational approaches.
AB  - The article considers the nature of the presumed social play deficit in autistic
      spectrum disorders (ASDs). The nature of play and its typical development is
      outlined and discussed in relation to play development in ASDs. It is suggested
      that social play is a confluence of two strands of development that are affected
      in autism: social and emotional development, and the cognitive development of
      play. It is shown that social play develops in a transactional way and in ASDs
      initial social difficulties prevent the development of social interaction, with
      its role in eliciting and enriching spontaneous play. At the same time, cognitive
      and affective difficulties prevent the play of children with autism developing to
      the extent of attracting other children and being of a complexity from which
      social play might develop. This cycle of impoverished play opportunities for
      children with ASDs may be broken through direct teaching and there are
      encouraging models of teaching social play with some success.

PMID- 14678676
TI  - A comparative review of early forms of object-directed play and parent-infant
      play in typical infants and young children with autism.
AB  - The article reviews the empirical evidence relating to the development of early
      solitary object and parent-infant play in typical infants and children diagnosed
      with autism. Whilst, collectively, the findings indicate that there may be both
      qualitative and quantitative differences in the early play of children with
      autism, relative to that of other children, it is also clear that significant
      gaps exist in our current knowledge. It is proposed that longitudinal studies,
      which make a detailed examination of the form and developmental trajectory of
      early play, are needed if we are to devise the most effective content, design and
      outcome measures for intervention programmes using play as a therapeutic medium.

PMID- 14678677
TI  - A review of research into pretend play in autism.
AB  - Autism is currently diagnosed, in part at least, on the basis of problems in
      imagination. The article reviews the empirical evidence of difficulties in
      pretend play in autism, and focuses in particular on individuals' ability to
      engage in pretence in free play conditions, to produce pretence in more
      structured situations, and to make sense of pretend actions carried out by
      another person. These data suggest that individuals with autism have a marked
      difficulty in producing pretend play, but one that is reduced by providing
      substantial structure to the play situation or by testing comprehension of
      pretence. The implications of these findings for theories of pretend play in
      autism, in terms of an inability to conceive of non-literal situations, a
      difficulty in imposing a pretend usage on an object, or a failure to gain a
      benefit from engaging in pretend play, are discussed.

PMID- 14678678
TI  - Play and language in children with autism.
AB  - It is well established that the play and language skills of children with autism
      are impaired. The article considers the relationship between these developments
      in typically developing children and children with autism. First, the evidence
      for a relationship between these two areas in typically developing children is
      reviewed. Despite many methodological differences between studies, this evidence
      supports a relationship, with specific developments emerging first in play and
      subsequently in language. Second, evidence for a relationship between play and
      language in children with autism is reviewed. From published and some previously
      unpublished data it is concluded that if there is a relationship between play and
      language in children with autism it is weak, if it exists at all. Finally, the
      implications of these findings are discussed and it is suggested that any
      relationship between play and language may be mediated by how children and their
      parents interact when they are playing.

PMID- 14678679
TI  - Behavioral approaches to promoting play.
AB  - A variety of techniques grounded in behavioral psychology, and more specifically
      in applied behavior analysis, have been established to increase and improve play
      skills in children with autistic spectrum disorders. This article introduces a
      set of efficacious methods, which range from highly structured techniques to more
      naturalistic strategies. It focuses on object play as other authors in the issue
      discuss social play in greater depth. Behavioral techniques that are reviewed
      include: discrete trial training, use of stereotyped behaviors to increase play
      skills, pivotal response training, reciprocal imitation training, differential
      reinforcement of appropriate behavior, in vivo modeling and play scripts, and
      video modeling. A discussion of expanding behavior techniques to teach more
      complex play as well as training in varied environments is also presented.
      References are provided to allow the reader to obtain more in-depth information
      about each technique.

PMID- 14678680
TI  - Promoting early play.
AB  - Early forms of play involving the exploration of objects is repetitive and
      limited in scope in children with autism, consistent with a weak drive towards
      central coherence. The importance is stressed of early manipulative and
      relational play for the development of meaningful perceptual representations and
      the subsequent development of functional and symbolic play. It is argued that
      intervention designed to promote these early forms of play is therefore of
      critical importance. A 'toy-play' intervention programme is described that was
      initially used in a research setting with 24 children with autism, using outcome
      measures and a 1 year follow-up assessment. The original intervention was
      successful. However, improvements in play were not maintained unless children
      continued to receive play support. A 'play stimulation' programme building on the
      toy-play programme is therefore now carried out with children in small groups
      after completion of the one-to-one toy-play programme.

PMID- 14678681
TI  - Climbing the symbolic ladder in the DIR model through floor time/interactive
      play.
AB  - The developmental, individual-difference, relationship-based model (DIR), a
      theoretical and applied framework for comprehensive intervention, examines the
      functional developmental capacities of children in the context of their unique
      biologically based processing profile and their family relationships and
      interactive patterns. As a functional approach, it uses the complex interactions
      between biology and experience to understand behavior and articulates the
      developmental capacities that provide the foundation for higher order symbolic
      thinking and relating. During spontaneous 'floor time' play sessions, adults
      follow the child's lead utilizing affectively toned interactions through gestures
      and words to move the child up the symbolic ladder by first establishing a
      foundation of shared attention, engagement, simple and complex gestures, and
      problem solving to usher the child into the world of ideas and abstract thinking.
      This process is illustrated by a case example of a young boy on the autism
      spectrum interacting with his father during 'floor time' over a 3 year period.

PMID- 14678682
TI  - Supporting children on the autism spectrum in peer play at home and school:
      piloting the integrated play groups model in Taiwan.
AB  - The article focuses on integrated play groups (IPGs) as a model to support
      children with ASD in play with typically developing peers/siblings, and its
      recent adoption with children in a home and school setting in Taiwan. The first
      part provides a brief overview of the IPG model and its essential features. The
      second part reports on a pilot investigation that combined quantitative and
      qualitative methods to examine the effects of participation in IPGs on the
      symbolic and social play of two early elementary-aged children with autism.
      Preliminary findings suggest that each child made notable gains in reciprocal
      social interaction and symbolic/pretend play while participating in play groups.
      Implications are discussed in terms of play's role in enhancing socialization,
      imagination and peer cultural inclusion.

PMID- 14678683
TI  - Beyond echoplaylia: promoting language in children with autism.
AB  - The article was written to support the use of play as a medium to extend and
      enrich the communicative exchanges and, more specifically, the symbolic language
      of children on the autistic spectrum. The first argument in support of such use
      of play lies within the features of autistic communication, and particularly the
      extreme challenges encountered in imaginative play and narrative thought. The
      second argument on behalf of play lies within the selection of specific
      intervention strategies, which are discussed subsequently. Finally, the article
      presents a case illustration of how adult facilitated dramatic peer play led to a
      breakthrough in a range of symbolic behaviours in a 9-year-old girl with autism,
      who up to that point had not progressed beyond a semi-communicative use of
      echolalia, best described as 'situation association'.

PMID- 14678684
TI  - Reflections on play: recollections from a mother and her son with Asperger
      syndrome.
AB  - This is a personal account of the play behaviors of an individual who has autism
      as remembered by himself and his mother. Jean-Paul Bovee explains the activities
      that were enjoyable for him and which were his play, although they were unusual
      and may not fit the typical definition of play. His mother, Dr Julie A. Donnelly,
      tells of her attempts to involve Jean-Paul in typical play and how important play
      is as a bridge to social skills and involvement with peers. Jean-Paul concludes
      that his play is a part of the unique individual he has become.

PMID- 14678693
TI  - [Childhood and adolescent obesity in Spain. Results of the enKid study (1998
      2000)].
AB  - BACKGROUND AND OBJECTIVE: Obesity is a chronic disease with a complex
      multifactorial nature which typically begins during childhood and adolescence. It
      represents one of today's most critical and escalating public health concerns for
      this segment of the population. The lack of obesity prevalence data at national
      level prompted the enKid Study (1998-2000), which was designed to evaluate the
      food habits and nutritional status of Spanish children and youth. SUBJECTS AND
      METHOD: Cross-sectional epidemiological study of a representative sample of the
      Spanish population aged 2 to 24 years (n=3534). Height and weight measurements
      were carried out using standard procedures and equipment. Obesity and overweight
      were defined according to BMI values for the 97th and 85th percentiles,
      respectively using Spanish reference data provided by Hernandez et al (1998).
      RESULTS: The prevalence of obesity in Spain is 13.9%, while the combination of
      overweight and obesity yields a prevalence of 26.3% (with a prevalence of
      overweight alone of 12.4%). Obesity is more common in males (15.6%) than in
      females (12%), which was also true for overweight. With regard to age, a higher
      prevalence is found among those aged 6 to 13 years. As for the geographic area,
      Canary Islands and Andalusia show the highest prevalence and the northeast region
      the lowest. Obesity is also more prevalent among those people with the lowest
      socio-economic and educational levels, and in those who omitted or consumed a
      poor breakfast. CONCLUSIONS: Compared to other countries, Spain shows an
      intermediate level of obesity in children and youth. Over the past decades, there
      has been an increasing trend towards overweight and obesity, which are more
      prevalent in males and during prepuberal ages.

PMID- 14678692
TI  - [Clinical characteristics of the fatal and near-fatal asthma in Alternaria
      alternata sensitized patients].
AB  - BACKGROUND AND OBJECTIVE: Some studies have pointed to Alternaria alternata as a
      trigger of fatal and near-fatal asthma (NFA) crises. The objective of this study
      was to determine the clinical characteristics of fatal and NFA crisis in patients
      sensitized to Alternaria. PATIENTS AND METHOD: One hundred ninety four patients
      with fatal or NFA attacks were enrolled in a multicenter (33 Spanish hospitals),
      prospective study. We gathered the characteristics and clinical course of the
      crises. We performed the following tests: spirometry, prick-test to common
      allergens, and specific IgE to Alternaria when patients were in stable condition.
      The sensitization test to Alternaria was performed when the prick-test and/or
      specific IgE levels were positive. RESULTS: Twenty (10%) patients were sensitized
      to Alternaria. When compared to non-sensitized patients, Alternaria sensitized
      patients were significantly younger, 35 (15) vs 50 (21) years old (p<0.001);
      their hospital admission length was shorter, 6.5 (5.5) against 9 (7) days
      (p=0.039); they had a higher number of deaths or severe neurological sequelae, 15
      vs 3% (p=0.026); they had a higher sensitization frequency to the remaining
      allergens, 68 against 22% (p=0.003); and they exhibited a fewer bronchodilation
      response upon inhaled salbutamol, 6 vs 10% (p=0.013). CONCLUSIONS: The clinical
      characteristics of Alternaria sensitised, fatal-and NFA-patients, seem to
      identify a particular phenotype. Specific avoidance strategies could be useful to
      prevent fatal and NFA attacks.

PMID- 14678694
TI  - [Alcoholism in the general hospital: detection and treatment].
AB  - BACKGROUND AND OBJECTIVE: Alcohol is an important factor in hospital admissions.
      Few publications have studied how alcoholics are handled in hospitals. PATIENTS
      AND METHOD: All inpatient referrals (IPC) to our Alcohol Unit (n=212) during 12
      months were analyzed. RESULTS: Four departments accounted for 80% of IPC, which
      represented 3% of all admissions in these departments. 72% of patients showed
      important psycho-social problems, 46% had had previous admissions to the
      hospital, and 21% had been visited by the Alcohol Unit earlier. Treatment was not
      offered at discharge to 20% of patients because of their severe psycho-social or
      physical deterioration. 17% of patients refused treatment. CONCLUSIONS:
      Alcoholism in inpatients is underdiagnosed. Only the most severe cases are
      detected. Those who might benefit the most are often undiagnosed.

PMID- 14678695
TI  - [Therapeutic compliance and near-fatal asthma].

PMID- 14678696
TI  - [Guidelines for the diagnosis, evaluation and treatment of hypertension: the
      point of view of the Spanish Society of Hypertension].

PMID- 14678697
TI  - [Health National Systems. Achilles heel. A point of view].

PMID- 14678698
TI  - [Role of cyclooxygenase-2 in the pathogenesis of chronic liver diseases].
AB  - Cyclooxygenase (COX) is a crucial enzyme in the biosynthesis of prostaglandins.
      There are two COX isoforms: COX-1 is constitutively expressed in a number of cell
      types and is involved in the homeostatic functions of prostaglandins, whereas COX
      2 is inducible by a variety of proinflammatory stimuli, such as cytokines and
      lipopolysaccharide. In the liver, COX-2 and prostaglandins production has been
      implicated in hepatic regeneration, liver matrix remodeling and portal
      hypertension. In animal models of alcoholic-induced liver disease has been
      demonstrated its relation with necro-inflammatory activity. In viral hepatitis,
      hepatocellular COX-2 expression was observed and associated with fibrosis
      progression. More interestingly it has been the demonstration of COX-2 role in
      the development of hepatocellular carcinoma and cholangiocarcinoma, such in
      experimental models as in human samples. It has also been demonstrated that COX-2
      was implicated in carcinogenesis through apoptosis inhibition and increased
      proliferation of human tumor cells. Experimental evidences show that selective
      pharmacologic inhibition of COX-2 could be useful in chemoprevention of primary
      liver tumors.

PMID- 14678699
TI  - [Oligoarthritis, trembling and chronic diarrhea in a 54 years old male].

PMID- 14678700
TI  - [Anticoagulation of pregnant women with mechanical heart valves].

PMID- 14678701
TI  - [Anxiety and depression in caregivers and patients with lymphoid neoplasm].

PMID- 14678702
TI  - [Colorectal adenocarcinoma in Crohn's disease].

PMID- 14678703
TI  - [Rheumatoid arthritis, pure red cell aplasia and large granular lymphocyte
      leukemia].

PMID- 14678704
TI  - [Eggs shells intake as a form of pica].

PMID- 14678705
TI  - [Immunization accessibility in immigrant population in Barcelona].

PMID- 14678706
TI  - [The bibliographic reference model used in the Internet address of the SEEIUC].

PMID- 14678707
TI  - [Critical care nursing and continuous renal replacement techniques in the Madrid
      Community].
AB  - The continuous renal replacement techniques (CRRT) aim to substitute the altered
      renal function during a period of time, presenting advantages compared to
      conventional hemodialysis (CH). This study aims to determine the situation of the
      CRRT in the Intensive care units (ICU) of the Madrid Community (MC) using a
      survey distributed to nurses (n = 131) of 14 ICU. It evaluates four aspects of
      the CRRT: management model, knowledge, problems and degree of satisfaction. It
      identified four models, the most frequent is that in which ICU nurse and
      intensivist participate (60%). Self-evaluation of knowledge was fair in 55.7% of
      the cases and the mean of correct responses in an evaluation of 10 questions was
      4.19 and 5.45 in those with previous courses. A total of 84.7% think that CRRT
      significantly increases the workloads and 62.6% believe that they should be done
      by the ICU nurses. The main problem is the lack of knowledge to resolve
      complications during the technique. We conclude that the ICU nursing can handle
      the CRRT, adapting the nurse/patient ratio; training programs should be
      established and the role of the teaching nurse defined in critical renal cares.

PMID- 14678708
TI  - [Accumulated fluid balance in patients admitted to the ICU: is it really
      reliable?].
AB  - In most of the textbooks, it is considered that the balance calculated after
      admission and the losses measured and/or estimated is an inexact way of
      establishing the real balance. Thus daily monitoring of the weight variations is
      recommended as a single possible alternative. On the other hand, there are few
      studies that have strictly studied the reliability of the fluid balance
      calculated. We also have not found any study in middle-long stay critical
      patients. These circumstances have led us to design an observational prospective
      study that will allow us to know if the accumulated balance calculated after
      admission and loses adequately reflect the weight changes in middle-long stay
      patients. We include 20 patients who were weighed every 48 hours (at least 3
      times each one) and we compare the weight changes with the balances calculated.
      We find that, above all after the 6th day, the accumulated balance calculated
      adequately reflected the weight changes (mean error/day < 250 ml), regardless of
      the presence or not of fever, sweat, oral diet, feces or mechanical ventilation.
      When weight on admission to the ICU was less than 75 kg, the changes in the
      balance calculated adjusted even more to the weight change, the contrary
      occurring when the weight was greater than 75 kg. These findings suggest that the
      accumulated balance calculated represents a valid alternative to daily weighing
      of the patients and that factors such as body mass and/or surface should be taken
      into account to reach more exact estimations.

PMID- 14678712
TI  - Commentary: changing paradigms in dermatology.

PMID- 14678709
TI  - [Acute myocardial infarction in the intensive care unit. Survival analysis].
AB  - INTRODUCTION: Acute myocardial infarction (AMI) is caused by total occlusion of
      the coronary artery lumen. Ischemic heart disease is the main cause of death in
      industrialized countries, it being more frequent in men, although more fatal in
      women. Its mortality rate increases after fifty years of age. OBJECTIVES: To
      perform a survival analysis of the patients with AMI diagnosis in the ICU of the
      Hospital of Cabuenes; to learn the relationship existing between the mortality
      rate, site and types of AMI. Patients and method. Retrospective descriptive study
      of 253 patients diagnosed of AMI in the year 2001 by review of clinical records
      and telephone follow-up. The variables used were age, gender, site and type of
      AMI. The SPSS statistical program was used to obtain the results. RESULTS: Age
      above 65 years and anterior site of AMI increase mortality. No significant
      differences are observed in regards to gender and electrocardiographic type. Post
      infarction mortality is very high in the first days, followed by a progressive
      decrease in the follow-up. CONCLUSION: Mortality is not conditioned by the
      different types of AMI and it is seen to be greater during the stay in the ICU.

PMID- 14678713
TI  - Changing paradigms in dermatology: science and art of diagnostic patch and
      contact urticaria testing.

PMID- 14678714
TI  - Changing paradigms in dermatology: new ways to examine the skin using noninvasive
      imaging methods.
AB  - Detailed visualization of the skin in the practice of dermatology is key to a
      comprehensive examination and accurate diagnosis. Advancements in digital
      dermoscopy, microscopy, imaging and photography have formed an impressive arsenal
      with which dermatologists can offer state-of-the-art patient care while
      streamlining their clinical practice and improving their academic and research
      capacities. Many types of advanced imaging are used in the biologic sciences at
      the bench; however, our paper reviews the clinical, noninvasive in vivo human
      applications of these emerging technologies. Our experiences with these
      instruments reinforce such reviews.

PMID- 14678715
TI  - Changing paradigms in dermatology: confocal microscopy in clinical and surgical
      dermatology.
AB  - The current practice of pathology and dermatopathology depends upon the
      evaluation of tissue in some manner extirpated from the patient and then
      processed and stained. While high resolution of detail can be accomplished by
      this method, there are certain risks and disadvantages. Recent imaging techniques
      now allow for a potential of achieving noninvasive high-resolution analysis of
      lesions in situ in the patient. Of these, Reflectance mode confocal microscopy
      offers the highest resolution imaging comparable to routine histology. Being
      entirely non invasive, skin can be observed in its native, dynamic state. This
      chapter will review the fundamentals of in vivo confocal imaging and the clinical
      applications in general and surgical dermatology.

PMID- 14678716
TI  - Changing paradigms in dermatology: proteomics: a new approach to skin disease.
AB  - Completion of the human genome sequence in 2001 heralded a new age in the
      understanding of cellular function. By eliminating the need for meticulous
      nucleotide identification of suspect proteins, a short segment can be identified
      and, within seconds the remaining sequences culled. Now, investigations can be
      more specifically targeted at the proteins themselves. Unlike the one gene, one
      protein approach of years past, proteomics is the field of unraveling the vast
      network of protein interactions within living cells. Recently, certain
      dermatologic conditions, such as psoriasis and eczema, have been shown to be the
      result of immune deregulation. By better understanding the proteins responsible
      for immune system function, targeted disruptions can alter tissue responses. It
      is in this vein that proteomics attempts to understand cellular regulation for
      the eventual therapeutic modification of biologic behavior.

PMID- 14678717
TI  - Changing paradigms in dermatology: information technology.
AB  - Medicine and specifically, dermatology, is undergoing enormous changes in the way
      in which it is practiced. Much of this is a result of a fundamental change in the
      manner in which information is exchanged through information technology. With the
      advent of more advanced telecommunications, imaging capabilities and information
      transfer, the very ways in which we examine patients, develop diagnoses and plan
      treatments as dermatologists have changed dramatically. This chapter will briefly
      review the development of personal computers and the Internet, as well as changes
      in telecommunications capabilities and how these changes have already altered how
      we see patients and care for them, as well as how new advances may continue to
      change the world of medicine and dermatology in the near future.

PMID- 14678718
TI  - Changing paradigms in dermatology: topical immunomodulators within a
      permutational paradigm for the treatment of atopic and eczematous dermatitis.
AB  - The first formulation of a class of products called topical immuno modulators
      (TIMS) was approved for clinical use in December 2000 and released in February
      2001. This product is tacrolimus in an ointment base, prescribed under the
      Protopic. The next TIM, pimecrolimus cream, was FDA approved in December 2001 and
      launched February 2002 in a cream vehicle under the Elidel. TIMs are becoming a
      significant component in the topical treatment paradigm for atopic dermatitis,
      introducing a useful alternative to, or complement for, high- and low-potency
      topical steroid therapy.

PMID- 14678719
TI  - Changing paradigms in dermatology: tumor necrosis factor alpha (TNF-alpha)
      blockade in psoriasis and psoriatic arthritis.
AB  - Psoriasis is an inflammatory T cell-mediated disease characterized by epidermal
      hyperplasia and parakeratosis, resulting in lesional areas of thick and scaling
      skin. Elevated levels of proinflammatory cytokines, including TNF-alpha, are
      found in psoriatic lesions. TNF-alpha has many effects in producing an
      inflammatory response such as stimulating production of pro-inflammatory
      molecules (eg, IL-1, IL-6, IL-8, NF-kappaB) and adhesion molecules (eg, ICAM-1, P
      selectin, E-selectin). As such, TNF-alpha is a target for immunotherapy in the
      treatment of psoriasis and psoriatic arthritis. The role of TNF-alpha in the
      pathogenesis of psoriasis is reviewed, along with clinical trials demonstrating
      the efficacy of new anti-TNF-alpha immunobiologics in the treatment of psoriasis
      and psoriatic arthritis.

PMID- 14678720
TI  - The modern paradigm of phototherapy.
AB  - The recognition of medical benefits obtained with suberythemogenic doses of
      natural sunlight extends back centuries. Modern medical application of
      phototherapy has been in place for over 100 years. It is the nature of scientific
      discovery to depend upon the use of new investigational methods or new devices to
      gain a better understanding of the mechanisms involved with the observed effects.
      Advancements in the field of photobiology and in the development of delivery
      systems for light therapy, such as narrow band UVB and laser, has given us
      additional insight into why and how phototherapy works in regards to treatment of
      skin disease and conditions of the skin. This discussion will primarily focus on
      ultraviolet light, photochemotherapy and a brief mention of photodynamic therapy.

PMID- 14678721
TI  - Changing paradigms in parasitic infections: common dermatological helminthic
      infections and cutaneous myiasis.
AB  - Parasitic diseases caused by helminths, or worms, account for billions of human
      infections worldwide. Although most human pathogens caused by these organisms are
      infrequent in the United States, skin manifestations of parasitic diseases are
      being seen much more frequently in dermatologists' offices due to the increase in
      immigration and travel. Helminths are notable for their complicated lifecycles
      often including consecutive developmental phases, in separate hosts or in a free
      living state. These parasitic organisms are usually macroscopic, multicellular
      organisms, and do not breed within their mammalian hosts. Notably, many
      helminthic diseases present with dermatologic signs and symptoms including skin
      nodules, cysts, migratory skin lesions, and pruritus. In this section, we discuss
      cutaneous myiasis as well as the four most common nematode dermatologic
      conditions seen in the United States.

PMID- 14678722
TI  - Superficial fungal infections: an update on pityriasis versicolor, seborrheic
      dermatitis, tinea capitis, and onychomycosis.
AB  - The recent advances in pityriasis versicolor, seborrheic dermatitis, tinea
      capitis and onychomycosis are reviewed. Some highlighted points include the new
      classification of Malassezia species, and the association of Malassezia species
      with seborrheic dermatitis. The use of terbinafine, fluconazole, and itraconazole
      for the treatment of tinea capitis is discussed. The management of onychomycosis,
      highlighting the high efficacy rates obtained with terbinafine when used to treat
      dermatophyte toenail onychomycosis, is discussed. The use of combination
      therapies in some circumstances to maximize cure rates is reviewed.

PMID- 14678723
TI  - Changing paradigms in dermatology: antivirals in dermatology.
AB  - Almost all of the approved antiviral drugs have become available during the past
      two decades. Approximately one half of these agents are for the treatment of
      human immunodeficiency virus (HIV) infections and comprise five classes. The
      first three classes all act to inhibit reverse transcriptase: nucleoside analogs;
      nonnucleoside analogs; and nucleotide analogs. The fourth class, protease
      inhibitors, prevent viral packaging; the fifth class, fusion inhibitors, prevent
      fusion between HIV and the target cell. Four nucleoside analogs, acyclovir,
      valacyclovir, famciclovir and penciclovir, are approved for the therapy of herpes
      simplex and varicella zoster infections. Interferon alpha is approved in the
      injectable form for condyloma acuminatum and Kaposi's sarcoma, but the more
      efficient method of delivering this agent is via interferon induction following
      topical use of imiquimod cream. Antiviral agents are also approved for infections
      with cytomegalovirus, hepatitis B and C, respiratory syncytial virus, and
      influenza viruses. Most of these antiviral drugs are virastatic and not
      viracidal. Vaccines and public health measures are much more effective and cost
      effective than antiviral drugs and must be promoted accordingly in the defense
      against viral infections.

PMID- 14678724
TI  - Changing paradigms in dermatology: nuclear hormone receptors.
AB  - Nuclear hormone receptors (NHRs) are a family of proteins that function similarly
      as nuclear transcription factors. The NHR family includes glucocorticoid
      receptors, retinoic acid and retinoid receptors, vitamin D receptors, thyroxin
      receptors, and peroxisome proliferator activated receptors. These proteins are
      targets for some of the most commonly prescribed medications in dermatology,
      including corticosteroids, retinoids, and vitamin D analogues, all of which have
      limiting side effects. Advances in this field have led to better understanding of
      the mechanisms of NHR therapeutic and toxic effects, receptor subtypes, tissue
      distribution, and interaction with other molecules. New generations of more
      specific NHR ligands designed to increase therapeutic efficacy and limit adverse
      effects have dramatically expanded the clinical application of NHR-targeting
      drugs. The current understanding of NHRs and future directions for NHR ligands in
      dermatology are discussed.

PMID- 14678725
TI  - It's time for a "change" in our approach to early detection of malignant
      melanoma.

PMID- 14678726
TI  - Correspondence to comments and controversy.

PMID- 14678728
TI  - Emerging viruses set to soar.
AB  - The emergence rate of novel viruses, such as the coronavirus that sparked SARS,
      could well be on the rise. Researchers now think that the SARS virus split from
      group 2 coronaviruses, and that this happened relatively recently on the scale of
      coronavirus evolution.

PMID- 14678729
TI  - Antibody diversity singled out.

PMID- 14678730
TI  - Death, where is thy sting?

PMID- 14678733
TI  - Matching targets for selective cancer therapy.

PMID- 14678734
TI  - Probiotics and prebiotics: why should the medical community pay attention?

PMID- 14678735
TI  - Ligand-selective signaling and high-content screening for GPCR drugs.

PMID- 14678736
TI  - The language of screening evolves.

PMID- 14678737
TI  - Nanotech approaches to drug delivery and imaging.
AB  - Nanotechnology, a multidisciplinary scientific undertaking, involves creation and
      utilization of materials, devices or systems on the nanometer scale. The field of
      nanotechnology is currently undergoing explosive development on many fronts. The
      technology is expected to create innovations and play a critical role in various
      biomedical applications, not only in drug delivery, but also in molecular
      imaging, biomarkers and biosensors. Target-specific drug therapy and methods for
      early diagnosis of pathologies are the priority research areas where
      nanotechnology would play a vital role. This review considers different
      nanotechnology-based drug delivery and imaging approaches, and their economic
      impact on pharmaceutical and biomedical industries.

PMID- 14678738
TI  - In silico multicellular systems biology and minimal genomes.
AB  - The in vivo and in silico understanding of genomes and networks in cellular and
      multicellular systems is essential for drug discovery for multicellular diseases.
      In silico methodologies, when integrated with in vivo engineering methods, lay
      the groundwork for understanding multicellular organisms and their genomes. The
      quest to construct a minimal cell can be followed by designed, minimal
      multicellular organisms. In silico multicellular systems biology will be
      essential in the design and construction of minimal genomes for minimal
      multicellular organisms. Advanced methodologies come to light that can aid drug
      discovery. These novel approaches include multicellular pharmacodynamics and
      networked multicellular pharmacodynamics.

PMID- 14678739
TI  - The growing impact of click chemistry on drug discovery.
AB  - Click chemistry is a modular approach that uses only the most practical and
      reliable chemical transformations. Its applications are increasingly found in all
      aspects of drug discovery, ranging from lead finding through combinatorial
      chemistry and target-templated in situ chemistry, to proteomics and DNA research,
      using bioconjugation reactions. The copper-(I)-catalyzed 1,2,3-triazole formation
      from azides and terminal acetylenes is a particularly powerful linking reaction,
      due to its high degree of dependability, complete specificity, and the bio
      compatibility of the reactants. The triazole products are more than just passive
      linkers; they readily associate with biological targets, through hydrogen bonding
      and dipole interactions.

PMID- 14678742
TI  - The metabolism of inorganic arsenic oxides, gallium arsenide, and arsine: a
      toxicochemical review.
AB  - The aim of this review is to compare the metabolism, chemistry, and biological
      effects to determine if either of the industrial arsenicals (arsine and gallium
      arsenide) act like the environmental arsenic oxides (arsenite and arsenate). The
      metabolism of the arsenic oxides has been extensively investigated in the past 4
      years and the differences between the arsenic metabolites in the oxidation states
      +III versus +V and with one or two methyl groups added have shown increased
      importance. The arsenic oxide metabolism has been compared with arsine (oxidation
      state -III) and arsenide (oxidation state between 0 to -III). The different
      metabolites appear to have different strengths of reaction for binding arsenic
      (III) to thiol groups, their oxidation-reduction reactions and their forming an
      arsenic-carbon bond. It is unclear if the differences in parameters such as the
      presence or absence of methyl metabolites, the rates of AsV reduction compared to
      the rates of AsIII oxidation, or the competition of phosphate and arsenate for
      cellular uptake are large enough to change biological effects. The arsine rate of
      decomposition, products of metabolism, target organ of toxic action, and protein
      binding appeared to support an oxidized arsenic metabolite. This arsine
      metabolite was very different from anything made by the arsenic oxides. The
      gallium arsenide had a lower solubility than any other arsenic compound and it
      had a disproportionate intensity of lung damage to suggest that the GaAs had a
      site of contact interaction and that oxidation reactions were important in its
      toxicity. The urinary metabolites after GaAs exposure were the same as excreted
      by arsenic oxides but the chemical compounds responsible for the toxic effects of
      GaAs are different from the arsenic oxides. The review concludes that there is
      insufficient evidence to equate the different arsenic compounds. There are
      several differences in the toxicity of the arsenic compounds that will require
      substantial research.

PMID- 14678743
TI  - Induction of glutathione S-transferase placental form positive foci in liver and
      epithelial hyperplasia in urinary bladder, but no tumor development in male
      Fischer 344 rats treated with monomethylarsonic acid for 104 weeks.
AB  - The carcinogenicity of monomethylarsonic acid (MMA(V)), a major metabolite of
      inorganic arsenics in human and experimental animals, was investigated in male
      Fischer 344 rats. A total of 129 rats at 10 weeks of age were randomly divided
      into three groups and received drinking water containing MMA(V) at doses of 0
      (Control), 50, and 200 ppm ad libitum for 104 weeks. No significant differences
      were found between the control and the MMA(V)-treated groups regarding clinical
      signs, mortality, hematological, and serum biochemistry findings. Quantitative
      analysis of glutathione S-transferase placental form (GST-P) positive foci in
      liver revealed a significant increase of numbers and areas in the 200 ppm MMA(V)
      treated group. In the urinary bladder MMA(V) induced simple hyperplasia and
      significantly elevated the proliferating cell nuclear antigen (PCNA)-positive
      index in the urothelium. A variety of tumors developed in rats of all groups,
      including the controls, but all were histologically similar to those known to
      occur spontaneously in F344 rats and there were no significant differences among
      the groups. Thus, it could be concluded that, under the present experimental
      conditions, MMA(V) induced lesions in the liver and urinary bladder, but did not
      cause tumor development in male F344 rats even after 2 years exposure.

PMID- 14678744
TI  - Lovastatin-induced cardiac toxicity involves both oncotic and apoptotic cell
      death with the apoptotic component blunted by both caspase-2 and caspase-3
      inhibitors.
AB  - The objective of this study was to evaluate the cardiac toxicity of the HMG-CoA
      reductase inhibitors by testing the hypothesis that lovastatin induces apoptotic
      and/or oncotic cell death in the myocyte element of the heart and further that
      cell death is mediated through interruption of the mevalonate pathway and that
      apoptosis is induced through activation of caspase-2 and caspase-3.
      Cardiomyocytes were cultured from embryonic chick heart. Lovastatin-induced
      apoptosis in these cells was demonstrated by three independent techniques, namely
      (1) FACS analysis of low DNA content by propidium iodide (PI); (2) microscopic
      assessment for cellular changes of apoptosis; and (3) FACS analysis of cells
      stained with PI and fluorescein diacetate. Lovastatin produced a concentration
      dependent increase in apoptotic cell death and 100 microM lovastatin showed over
      a 4-fold increase in apoptosis compared to control. Lovastatin also induced
      oncotic cell death, as there was a 2.5-fold increase in the amount of oncotic
      cell death compared to control. Lovastatin-induced apoptosis operated, in part,
      through the mevalonate pathway. The caspase-2 inhibitor z-VDVAD-fmk and the
      caspase-3 inhibitor Ac-DEVD-CHO reduced the extent of lovastatin-induced cardiac
      apoptosis. In contrast, lovastatin-induced oncosis was not only insensitive to
      these caspase-2 or -3 inhibitors but occurred through a mevalonate-independent
      mechanism of action. In summary, lovastatin-induced cardiotoxicity is complex and
      represents the sum of two distinct modes of cell death operating in part through
      the mevalonate pathway with the apoptotic component subject to modification by
      inhibitors of the initiator caspase, caspase-2, as well as the effector caspase,
      caspase-3.

PMID- 14678745
TI  - Possible mechanisms underlying the mitogenic action of heptachlor in rat
      hepatocytes.
AB  - The worldwide use of the organochlorine pesticide heptachlor has led to
      widespread contamination in the environment. Like many other organochlorine
      pesticides, heptachlor is considered to pose a threat to human health. It has
      been shown that heptachlor is a tumor-promoting agent, but the mechanisms
      involved still remain unclear. The negative response of heptachlor in in vitro
      genotoxicity test suggests that this pesticide displays its carcinogenicity
      through epigenetic pathways. With the growing evidence that proliferation
      accounts for the tumor-promoting effects of many agents, the purpose of this work
      was to investigate the mechanisms involved in the mitogenic activity of
      heptachlor in quiescent rat hepatocytes and to understand the properties of this
      compound as a tumor promoter in the liver. Heptachlor triggered significant
      proliferation in quiescent rat hepatocytes. Two mechanisms were delineated to
      support the mitogenic effect in the hepatocyte: activation of key kinases in
      signaling pathways and inhibition of apoptosis. Exposure to heptachlor led to
      activation of protein kinase C mitogenactivated protein kinases. Moreover, these
      results indicate that like many tumor promoters, heptachlor strongly inhibited
      TGFbeta-induced apoptosis and cytochrome c release into the cytosol. The levels
      of the anti-apoptotic protein Bcl-2 were also increased in the presence of
      heptachlor. In conclusion, these results indicate that heptachlor alters basic
      cell function by interfering with key cellular signaling pathways.

PMID- 14678746
TI  - Zebrafish embryos express an orthologue of HERG and are sensitive toward a range
      of QT-prolonging drugs inducing severe arrhythmia.
AB  - A wide range of drugs has been shown to prolong the QT interval of the
      electrocardiogram by blocking the pore-forming subunit of the rapidly activating
      delayed rectifier K+ channel, HERG (ether-a-go-go-related gene), sometimes
      leading to life-threatening arrhythmia. In this paper we describe cloning,
      sequence, and expression of the zebrafish orthologue of HERG, Zerg. Further, we
      studied effects of Zerg inhibition in zebrafish embryos caused by drugs or by an
      antisense approach. Zerg is expressed specifically in both heart chambers of
      zebrafish embryos, is composed of six transmembrane domains, and shows an
      especially high degree of amino acid conservation in the S6 and pore domain (99%
      identity). Several QT-prolonging drugs added to the bathing medium elicited
      bradycardia and arrhythmia in zebrafish embryos. The arrhythmia induced ranged
      from an atrioventricular 2:1 block, the ventricle beating half as often as the
      atrium, to more severe irregular arrhythmia with higher concentrations of the
      drugs. These effects were highly specific, reproducible, and rapid, e.g., 10
      microM astemizole caused a 2:1 heartbeat within a minute after addition of the
      compound in all the embryos studied. Morpholino antisense oligonucleotides
      targeting Zerg were injected into zebrafish embryos and elicited similar dose
      sensitive and specific arrhythmia as the QT-prolonging drugs, suggesting an
      evolutionarily conserved role for Erg in regulating heartbeat rate and rhythm.
      Further, we identified a mutation in the Per-Arnt-Sim domain of the Zerg channel
      in the breakdance mutant, also characterized by a 2:1 atrioventricular block. In
      conclusion, the zebrafish could be a tractable model organism for the study of
      Erg function and modulation but might also have a value in the field of
      cardiovascular pharmacology, e.g., as an early preclinical model for testing
      drugs under development for potential QT prolongation.

PMID- 14678747
TI  - Cytoplasmic vacuolation in cultured rat astrocytes induced by an organophosphorus
      agent requires extracellular signal-regulated kinase activation.
AB  - There are various toxic chemicals that cause cell death. However, in certain
      cases deleterious agents elicit various cellular responses prior to cell death.
      To determine the cellular mechanisms by which such cellular responses are induced
      is important, but sufficient attention has not been paid to this issue to date.
      In this study, we showed the characteristic effects of an organophosphorus (OP)
      agent, bis(pinacolyl methyl)phosphonate (BPMP), which we synthesized for the
      study of OP nerve agents, on cultured rat astrocytes. Morphologically, BPMP
      induced cytoplasmic vacuolation and stellation in the rat astrocytes. Cytoplasmic
      vacuolation is a cell pathological change observed, for example, in vacuolar
      degeneration, and stellation has been reported in astrocytic reactions against
      various stimuli. By pretreatment with cycloheximide, a protein synthesis
      inhibitor, stellation was inhibited, although vacuolation was not. Cell staining
      with a mitochondrion-selective dye indicated that the vacuolation probably occurs
      in the mitochondria that are swollen and vacuolatred in the center.
      Interestingly, the extracellular signal-regulated kinase (ERK) cascade inhibitor
      inhibited vacuolation and, to some extent, stellation. These results suggest that
      the ERK signaling cascade is important for the induction of mitochondrial
      vacuolation. We expect that a detailed study of these astrocytic reactions will
      provide us new perspectives regarding the variation and pathological significance
      of cell morphological changes, such as vacuolar degeneration, and also the
      mechanisms underlying various neurological disorders.

PMID- 14678748
TI  - Poly(ADP-ribose) polymerase-1 and apoptosis inducing factor in neurotoxicity.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is the guardian of the genome acting as a
      sentinel for genomic damage. However, PARP-1 is also mediator of cell death after
      ischemia-reperfusion injury, glutamate excitotoxicity, and various inflammatory
      processes. The biochemistry underlying PARP-1-mediated cell death has remained
      elusive, although NAD(+) consumption and energy failure have been thought to be
      one of the possible molecular mechanisms. Recent observations link PARP-1
      activation with translocation of apoptosis-inducing factor (AIF) to the nucleus
      and indicate that AIF is an essential downstream effector of PARP-1-mediated cell
      death. PARP-1 activation signals AIF release from the mitochondria, resulting in
      a novel, caspase-independent pathway of programmed cell death. These recent
      findings suggest that AIF maybe a target for development of future therapeutic
      treatment for many neurological disorders involving excitotoxicity.

PMID- 14678749
TI  - Gender differences in the amount and deposition of amyloidbeta in APPswe and PS1
      double transgenic mice.
AB  - Transgenic mice carrying both the human amyloid precursor protein (APP) with the
      Swedish mutation and the presenilin-1 A246E mutation (APP/PS1 mice) develop
      Alzheimer's disease-like amyloidbeta protein (Abeta) deposits around 9 months of
      age. These mice show an age-dependent increase in the level of Abeta40 and
      Abeta42 and in the number of amyloid plaques in the brain. Abeta40 and Abeta42
      levels were measured, and amyloid burden and plaque number were quantified, in
      the hippocampus at the age of 4, 12, and 17 months in both male and female
      APP/PS1 mice. In all mice, amyloid burden and plaque number increased markedly
      with age, with female mice bearing a heavier amyloid burden and higher plaque
      number compared to male mice of the same age, both at 12 and at 17 months of age.
      The level of both Abeta40 and Abeta42 significantly increased in female mice with
      age and was always significantly higher in female than in male mice of the same
      age. Further, there were significant correlations between amyloid burden and
      Abeta42 level in female mice and between amyloid burden and plaques in both
      female and male mice. Together these data show that female APP/PS1 mice
      accumulate amyloid at an earlier age and that they build up more amyloid deposits
      in the hippocampus than age-matched male mice. Together, these results provide
      new insights in the potential mechanisms of the observed gender differences in
      the pathogenesis of AD.

PMID- 14678750
TI  - AGS-induced expression of Narp is concomitant with expression of AMPA receptor
      subunits GluR1 and GluR2 in hippocampus but not inferior colliculus of P77PMC
      rats.
AB  - To explore mechanisms of epileptogenesis in audiogenic seizures (AGS), we
      examined the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazoleopropionic
      acid (AMPA) receptor subunits GluR1 and GluR2 and of the GluR-associated protein
      Narp in the hippocampus and the inferior colliculus (IC) from AGS-susceptible
      P77PMC rats after a single AGS and audiogenic kindling. Western blotting and
      immunohistochemistry showed that Narp was rapidly induced in both the hippocampus
      and the IC by AGS. In the hippocampus, up-regulation of Narp was concomitant with
      GluR1 and GluR2 under both conditions of a single AGS and AGS kindling. In the
      IC, however, Narp was up-regulated, GluR2 down-regulated, and GluR1 unchanged
      after kindling. In comparison with kindling, neither GluR1 nor GluR2 was changed,
      while Narp significantly increased in the IC following a single AGS. These
      findings suggest that down-regulation of AMPA receptor GluR2 subunit in the IC
      may contribute to AGS-mediated epileptogenesis, and up-regulation of Narp in the
      IC may be involved in audiogenic seizures.

PMID- 14678751
TI  - AMPA receptors are the major mediators of excitotoxic death in mature
      oligodendrocytes.
AB  - Myelination of axons is important for central nervous system function, but
      oligodendrocytes, which constitute CNS myelin, are vulnerable to excitotoxic
      injury and death. Although mature oligodendrocytes express functional alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) and kainate-type glutamate
      receptors, the relative roles of these subtypes in excitotoxicity are not well
      understood. Using recently developed selective antagonists for subtypes of
      ionotropic non-NMDA receptors, we addressed this issue. By examining the
      pharmacological, biochemical, and morphologic features of kainite-induced
      excitotoxic death, we also determined whether it occurs by apoptosis, necrosis,
      or both. We conclude that when mature oligodendrocytes die after exposure to
      kainate: (1) AMPA receptors are the most important mediators, (2) kainate
      receptors play a smaller role, and (3) death occurs predominantly by necrosis,
      not apoptosis.

PMID- 14678752
TI  - Overexpression of the chromosome 21 transcription factor Ets2 induces neuronal
      apoptosis.
AB  - Down syndrome (trisomy 21) neurons display an increased rate of apoptosis in
      vitro. The genes on chromosome 21 that mediate this increased cell death remain
      to be elucidated. Here we show that the chromosome 21 transcription factor Ets2,
      a gene that is overexpressed in Down syndrome, is expressed in neurons, and that
      moderate overexpression of Ets2 leads to increased apoptosis of primary neuronal
      cultures from Ets2 tg mice that involves activation of caspase-3. Our data
      therefore suggest that overexpression of ETS2 may contribute to the increased
      rate of apoptosis of neurons in Down syndrome.

PMID- 14678753
TI  - The C289G and C418R missense mutations cause rapid sequestration of human Parkin
      into insoluble aggregates.
AB  - Mutations in the parkin gene are responsible for autosomal recessive
      parkinsonism. The disease-linked missense mutations are highly concentrated in
      the RING-IBR-RING domains of Parkin. In this study, we investigated the
      consequences of several missense parkin gene mutations in cell culture. We have
      demonstrated that two of these mutations (C289G and C418R), which replace
      consensus cysteine residues in the RING domains, significantly decrease the
      solubility of Parkin in cells. Upon overexpression, the presumably misfolded
      proteins formed cytoplasmic aggregates that concentrated into large perinuclear
      inclusion bodies when proteasome activity was inhibited. This process required
      active microtubule-dependent retrograde transport, as previously reported for
      aggresome formation. These results provide information on the molecular basis of
      the loss of function caused by mutations of critical residues in Parkin. They
      also contribute to our understanding of the cellular mechanism underlying the
      aggregation of mutant Parkin.

PMID- 14678754
TI  - A novel recombinant adeno-associated virus vaccine reduces behavioral impairment
      and beta-amyloid plaques in a mouse model of Alzheimer's disease.
AB  - Memory impairment progressing to dementia is the main clinical symptom of
      Alzheimer's disease (AD). Deposition of the amyloid-beta peptide (Abeta) in
      brain, particularly its 42-amino acid isoform (Abeta42), has been shown to play a
      primary and crucial role in the pathogenesis of AD. In this study we have
      developed a recombinant adeno-associated virus (AAV) vaccine against AD. This
      vaccine could express CB-Abeta42 (cholera toxin B subunit and Abeta42 fusion
      protein) in vivo. A single administration of the AAV-CB-Abeta42 vaccine induced a
      prolonged, strong production of Abeta-specific serum IgG in transgenic mice that
      overexpressed the London mutant of amyloid precursor protein (APP/V717I), and
      resulted in improved ability of memory and cognition, decreased Abeta deposition
      in the brain, and a resultant decrease in plaque-associated astrocytosis. Our
      results extended the immunological approaches for the treatment and prevention of
      AD to an oral, intranasal, or intramuscular route that might be better tolerated
      in human patients than repetitive parental immunizations in the presence of
      adjuvant. AAV has attracted tremendous interest as a promising vector for gene
      delivery. Our results raised the possibility that AAV-CB-Abeta42 vector
      immunization may provide the basis of a novel and promising Alzheimer's disease
      vaccination program.

PMID- 14678755
TI  - Chronic hyperammonemia alters motor and neurochemical responses to activation of
      group I metabotropic glutamate receptors in the nucleus accumbens in rats in
      vivo.
AB  - Hyperammonemia leads to altered cerebral function and neurological alterations in
      patients with hepatic encephalopathy. We studied the effects of hyperammonemia in
      rats on the modulation by group I metabotropic glutamate receptors (mGluR) of
      motor and neurochemical functions in vivo. Locomotion induced by injection of the
      mGluR agonist DHPG into nucleus accumbens was increased in hyperammonemic rats.
      In control rats DHPG increased extracellular dopamine (ca. 400%) but not
      glutamate. In contrast, in hyperammonemic rats DHPG increased extracellular
      glutamate (ca. 600%), while DHPG-induced dopamine increase was reduced. Blocking
      mGluR1 receptor with CPCCOEt prevented all DHPG effects, indicating that this
      receptor mediates its locomotor and neurochemical effects. Hyperammonemic rats
      showed increased (32%) mGluR1alpha, but not mGluR5 content in nucleus accumbens.
      These results show that modulation of locomotor and neurochemical functions by
      mGluRs in nucleus accumbens is strongly altered in hyperammonemia. These
      alterations may contribute to the neurological alterations in hyperammonemia and
      liver failure.

PMID- 14678756
TI  - Accumulation of caspase cleaved amyloid precursor protein represents an early
      neurodegenerative event in aging and in Alzheimer's disease.
AB  - The activation of caspase-3 and possibly other caspases during apoptosis may lead
      to the cleavage of the amyloid precursor protein (APP) and subsequent
      accumulation of APP cleavage products (cAPP). We examined the association between
      activated caspase-3 and cAPP in human brain by qualitative and quantitative
      analysis of in situ immunohistochemistry and Western blots. Frontal cortex and
      hippocampal tissue from age-matched control and Alzheimer's brains (AD) was used.
      Both activated caspase-3 and cAPP are increased in AD [Braak and Braak (BB) stage
      IV-VI] compared to aged control (BB stage 0-1) and transitional (BB stage II-III)
      cases in the hippocampal and frontal cortex. Caspase-3 activation and the
      accumulation of APP cleavage fragments appear to either parallel or precede
      neurofibrillary tangle formation. These findings raise the possibility that the
      activation of caspase-3 and cleavage of APP may be involved with neuronal
      degeneration and that pathways characteristic of apoptosis are activated in AD.

PMID- 14678757
TI  - Levodopa-induced motor complications are associated with alterations of glutamate
      receptors in Parkinson's disease.
AB  - Glutamate receptors were studied in the brains of controls and Parkinson's
      disease (PD) patients, of which 10 of 14 developed motor complications
      (dyskinesias and/or wearing-off) following levodopa therapy. (125)I-RTI binding
      to the dopamine transporter and dopamine concentrations show comparable
      nigrostriatal denervation between the subgroups of PD patients. (3)H-Ro 25-6981
      binding to the NR1/NR2B NMDA receptor was increased in the putamen of PD patients
      experiencing motor complications compared to those who did not (+53%) and
      compared to controls (+18%) whereas binding remained unchanged in the caudate
      nucleus. (3)H-AMPA binding was increased in the lateral putamen (+23%) of PD
      patients with motor complications compared to those without whereas it was
      decreased in the caudate nucleus of the PD patients (-16%) compared to controls.
      Caudate and putamen (3)H-CGP39653 binding to NR1/NR2A NMDA receptor and NR1
      subunit mRNA levels measured by in situ hybridization were unchanged in subgroups
      of PD patients compared to controls. These findings suggest that glutamate
      receptor supersensitivity in the putamen plays a role in the development of motor
      complications (both wearing-Off and dyskinesias) following long-term levodopa
      therapy in PD.

PMID- 14678758
TI  - Involvement of benzodiazepine receptors in neuroinflammatory and
      neurodegenerative diseases: evidence from activated microglial cells in vitro.
AB  - Increased binding of a ligand for the peripheral benzodiazepine binding receptor
      is currently used in PET studies as an in vivo measurement of inflammation in
      diseases like multiple sclerosis and Alzheimer's disease. Although peripheral
      type benzodiazepin receptors (PBRs) are abundant in many cell types and expressed
      in the CNS physiologically only at low levels, previous reports suggest that
      after experimental lesions in animal models and in human neurodegenerative/
      inflammatory diseases upregulated PBR expression with increased binding of its
      ligand PK11195 is confined mainly to activated microglia in vivo/in situ. Because
      the functional role of the PBR is unknown, we confirm by immunohistochemistry and
      PCR (I) that this receptor is expressed on microglia in vitro and (II) that
      benzodiazepines modulate proliferation of microglial cells and the release of the
      inflammatory molecules nitric oxide (NO) and tumor necrosis factor-alpha (TNF
      alpha) in cell culture supernatants of primary rat microglia. Compared to
      lipopolysaccharide-activated controls the release of NO was markedly decreased in
      cultures treated with benzodiazepines (clonazepam, midazolam, diazepam) and the
      PBR ligand PK11195. Moreover, release of TNF-alpha and proliferation was
      significantly inhibited in the benzodiazepine-treated groups. These findings link
      the in vivo data of elevated PBR levels in neurodegenerative/-inflammatory
      diseases to a functional role and opens up possible therapeutic intervention
      targeting the PBR in microglia.

PMID- 14678759
TI  - Correlation of very long chain fatty acid accumulation and inflammatory disease
      progression in childhood X-ALD: implications for potential therapies.
AB  - This study was designed to understand the role of inflammatory mediators involved
      in the neurobiology of childhood adrenoleukodystrophy (cALD) by comparing the
      differential expression of the inflammatory mediators with metabolite very long
      chain fatty acids that accumulate in this disease. Histopathological examinations
      indicated extensive demyelination and accumulation of infiltrates in perivascular
      cuffs in plaque area (PA) and inflammatory area (IA) compared to normal looking
      area (NLA) of the cALD brain and controls. The PA had excessive accumulation of
      cholesterol ester (25-30-fold), VLC fatty acids (8-12-fold), and exhaustive
      depletion of cholesterol (60-70%) and sphingomyelin (50-55%) in comparison to
      controls. The mRNA expression of cytokines (IL-1alpha, IL-2, IL-3, IL-6, TNF
      alpha, and GM-CSF), chemokines (CCL2, -4, -7, -11, -16, -21, -22, CXCL1, CX3CL1,
      and SDF-2) and iNOS in IA was significantly increased compared to NLA of the cALD
      and controls determined by gene array, semiquantitative RT-PCR, and
      immunohistochemistry. These results indicate that accumulation of VLC fatty acid
      contents in membrane domains associated with signal transduction pathways may
      trigger the inflammatory process through activation of resident glial cells
      (microglia and astrocytes) resulting in loss of myelin and oligodendrocytes.

PMID- 14678761
TI  - Acetylcholinesterase induces the expression of the beta-amyloid precursor protein
      in glia and activates glial cells in culture.
AB  - Acetylcholinesterase (AChE) activities in CNS physiopathology are increasingly
      diverse and range from neuritogenesis, through synaptogenesis, to enhancement of
      amyloid fiber assembly. In Alzheimer's disease, senile plaques and
      neurodegeneration specially affect regions enriched for cholinergic synapses. In
      this study we show an effect of AChE that could contribute to the increased
      deposition of Abeta in certain regions. Affinity-purified AChE induced the
      expression of amyloid-beta-precursor protein (beta-APP) in glial cells in a
      concentration-dependent manner up to 5 nM. In glia, AChE also increased inducible
      nitric oxide synthase (iNOS) assessed by immunocytochemistry and decreased
      reductive metabolism as evidence of cell activation. AChE could increase the
      expression of beta-APP in astrocytes and microglia as result of the activation of
      glial cells. As a whole, we found that AChE has additional effects that could
      result in an increased synthesis of Abeta, both by increasing beta-APP expression
      of astrocytes and by further activating glial cells.

PMID- 14678760
TI  - Intermittent hypoxia induces time-dependent changes in the protein kinase B
      signaling pathway in the hippocampal CA1 region of the rat.
AB  - Intermittent hypoxia (IH) during sleep induces temporally defined increases in
      apoptosis within vulnerable brain regions such as the hippocampal CA1 region in
      rats. Protein kinase B (AKT) has emerged as major signal transduction protein
      underlying inhibition of apoptosis and consequent increases in cell survival.
      Sprague Dawley adult male rats were exposed during sleep to IH or to normoxia
      (RA) for periods ranging from 0 to 30 days, and expression of total and
      phosphorylated AKT, of forkhead family members FKHR and FKHRL1, and of glycogen
      synthase kinase 3beta (GSK3beta) was assessed. Decreases in phosphorylation
      occurred as early as 1 h IH exposure, reached a nadir at 6 h-3 days, and then
      progressively returned to baseline levels at 14-30 days. Phosphorylated AKT and
      GSK3beta were intensely expressed and highly colocalized within neuronal cells
      (Neu-N positive) in the CA1 region. Thus, IH induces time-dependent biphasic
      changes in AKT survival pathways within the CA1 region that are temporally
      correlated with the initial increases and subsequent decreases in neuronal
      apoptosis.

PMID- 14678762
TI  - Impairment of phosphatase 2A contributes to the prolonged MAP kinase
      phosphorylation in Alzheimer's disease fibroblasts.
AB  - The serine/threonine phosphatase 2A (PP2A) has been implicated in the
      pathogenesis of Alzheimer's disease (AD) due to its important role in regulating
      dephosphorylation of the microtubule-associated protein tau and mitogen-activated
      protein (MAP) kinase. In the present study, we show that PP2A was responsible for
      dephosphorylation of the extracellular signal-regulated kinase 1/2 (Erk1/2)
      following its activation by BK stimulation. Abnormal gene and protein expressions
      of PP2A, as well as its activity, were found to contribute to the abnormally
      prolonged Erk1/2 phosphorylation in the AD fibroblasts. Inhibition of PP2A with
      okadiac acid produced enhanced and more lasting Erk1/2 phosphorylation after BK
      stimulation, whereas FK506, an inhibitor of PP2B and FK-binding protein,
      inhibited the BK-stimulated Erk1/2 phosphorylation. Furthermore, while the
      phosphorylated Erk1/2 was concentrated in the nucleus of AC cells, it was mainly
      distributed in the extranuclear compartments of AD cells. These results suggest
      that the delayed dephosphorylation of Erk1/2 in AD cells following its BK
      stimulated activation may be due to deficits of PP2A activity and impaired
      nuclear translocation of phosphorylated Erk1/2.

PMID- 14678763
TI  - The same TCR (N)Dbeta(N)Jbeta junctional region is associated with several
      different vbeta13 subtypes in a multiple sclerosis patient at the onset of the
      disease.
AB  - In multiple sclerosis (MS), the T-cell receptors (TCRS) of autoreactive T
      lymphocytes recognize various myelin components or derivatives including peptides
      of the myelin basic protein (MBP). Using the exhaustive immunoscope approach we
      showed that the T-cell repertoires of MS patients differ from those of healthy
      controls, with expansion of Vbeta13 cell clones in cerebrospinal fluid (CSF) and
      in peripheral blood lymphocytes (PBLs). Sequencing of the beta13(+) chains of T
      cells recovered from the CSF revealed high interindividual diversity, and no
      particular Vbeta13(+) rearrangements were shown to be myelin-autoreactive. Within
      the overall Vbeta13 repertoire in the CSF of patient MS3 at the onset of the
      disease, most of the overrepresented (N)Dbeta(N)Jbeta junctional regions were
      found to be associated with two or three different Vbeta13 segments. These
      rearrangements were most common in the PBLs of patient MS3. No such associations
      were detected in the Vbeta5 multigene family that was used as a control. Thus,
      Vbeta13 T cells infiltrating the CSF from patient MS3 may have been selected on
      the basis of both the Vbeta13 segments and the (N)Dbeta(N)Jbeta junctional CDR3
      sequence.

PMID- 14678764
TI  - Status epilepticus-induced changes in the subcellular distribution and activity
      of calcineurin in rat forebrain.
AB  - This study was performed to determine the effect of prolonged status epilepticus
      on the activity and subcellular location of a neuronally enriched, calcium
      regulated enzyme, calcineurin. Brain fractions isolated from control animals and
      rats subjected to pilocarpine-induced status epilepticus were subjected to
      differential centrifugation. Specific subcellular fractions were tested for both
      calcineurin activity and enzyme content. Significant, status epilepticus-induced
      increases in calcineurin activity were found in homogenates, nuclear fractions,
      and crude synaptic membrane-enriched fractions isolated from both cortex and
      hippocampus. Additionally, significant increases in enzyme levels were observed
      in crude synaptic fractions as measured by Western analysis. Immunohistochemical
      studies revealed a status epilepticus-induced increase in calcineurin
      immunoreactivity in dendritic structures of pyramidal neurons of the hippocampus.
      The data demonstrate a status epilepticus-induced increase in calcineurin
      activity and concentration in the postsynaptic region of forebrain pyramidal
      neurons.

PMID- 14678765
TI  - Glia activation and cytokine increase in rat hippocampus by kainic acid-induced
      status epilepticus during postnatal development.
AB  - In adult rats, status epilepticus (SE) induces cytokine production by glia
      especially when seizures are associated with neuronal injury. This suggests that
      cytokines may play a role in seizure-induced neuronal damage. As SE-induced
      injury is age-specific, we used rats of different ages (with distinct
      susceptibilities to seizure-induced neuronal injury) to elucidate the role of
      cytokines in this process. Thus, we investigated the activation of microglia and
      astrocytes, induction of cytokines, and hippocampal neuronal injury 4 and 24 h
      following kainic acid-induced SE in postnatal day (PN) 9, 15, and 21 rats. At
      PN9, there was little activation of microglia and astrocytes at any time point
      studied. Interleukin-1beta (IL), tumor necrosis factor-alpha (TNF), and IL-6 or
      the naturally occurring IL-1 receptor antagonist (Ra) mRNA expression did not
      increase. No evidence of cell injury has been detected. At PN15, immunostaining
      of microglia and astrocytes was enhanced, but only IL-1beta mRNA expression was
      increased. These changes were observed 4 h after SE. Scattered injured neurons in
      CA3 and subiculum, but not in any other region, were present 24 h following SE.
      At PN21, immunostaining of microglia and astrocytes and the mRNA expression of
      all cytokines studied was significantly increased already 4 h after SE. At 24 h,
      many injured neurons were present in CA1 and CA3 regions and in 40% of rats in
      other forebrain areas. These data show that (i) the pattern of glia activation
      and cytokine gene transcription induced by SE is age-dependent and (ii) neuronal
      injury in the hippocampus occurs only when cytokines are induced and their
      synthesis precedes the appearance of neuronal damage. Thus, cytokine expression
      in immature brain is associated specifically with cell injury rather than with
      seizures per se, suggesting that proinflammatory cytokines may contribute to the
      occurence of SE-induced hippocampal damage.

PMID- 14678766
TI  - Functional analysis of plasma alpha(2)-macroglobulin from Alzheimer's disease
      patients with the A2M intronic deletion.
AB  - alpha(2)-Macroglobulin (alpha(2)M) is an abundant plasma/extracellular space
      protein implicated in clearance of amyloid beta (Abeta), a key constituent of
      Alzheimer's disease (AD) plaques. alpha(2)M also regulates proteinase and growth
      factor activities. In recent years, there have been >30 genetic studies debating
      the controversial role of a five-base-pair intronic deletion in the A2M gene in
      late-onset AD. However, little is known about potential effects of the deletion
      upon alpha(2)M function. In this study, we examined the subunit and
      conformational structure of alpha(2)M in AD plasma samples, and its capacity to
      bind trypsin, transforming growth factor-beta1, and Abeta. Plasma from patients
      homozygous for the deletion (DD) showed normal alpha(2)M subunit size,
      conformation, and proteinase inhibitory activity. Interestingly, plasma alpha(2)M
      from two DD patients showed markedly increased TGF-beta1 binding. Moreover,
      methylamine-treated DD plasma samples showed modest, but significant, elevations
      in Abeta binding to alpha(2)M* compared with samples from patients lacking the
      deletion. These observations suggest a possible functional basis by which the A2M
      deletion may influence multifactorial AD pathogenesis.

PMID- 14678767
TI  - Death mechanisms in status epilepticus-generated neurons and effects of
      additional seizures on their survival.
AB  - Status epilepticus (SE) increases neurogenesis in the subgranular zone (SGZ) of
      the adult dentate gyrus, but many of the newborn cells die, partly through
      caspase-induced apoptosis. Here we provide immunohistochemical evidence
      indicating that the caspase-evoked death of the new neurons involves the
      mitochondrial but not the death-receptor-mediated pathway. Cytochrome c released
      from mitochondria was found in a subset of progenitor cell progeny, while Fas
      ligand and tumor necrosis factor 1 receptor-associated domain as well as the
      mitochondria-related, caspase-independent apoptosis-inducing factor were not
      detected. We also show that additional seizures, induced at different stages
      during neuronal differentiation of progenitor cell progeny following SE, neither
      potentiate cell death mechanisms in the SGZ nor compromise the survival of the
      new cells. Thus, we found similar expression of cytochrome c, active caspase-3,
      caspase-cleaved PARP, and TUNEL/Hoechst-positive DNA fragmentation, as well as
      numbers of new cells in the SGZ in rats exposed to additional seizures at days 6
      and 7 or days 33 and 34 following SE as in control animals only subjected to SE.
      We propose that the degree of survival of newly generated neurons is determined
      primarily by the initial SE insult and the ensuing pathology in the tissue
      environment, whereas spontaneous seizures play a minor role.

PMID- 14678768
TI  - Regulation of hypoxia-inducible factor 1alpha and induction of vascular
      endothelial growth factor in a rat neonatal stroke model.
AB  - Stroke is a devastating condition occurring in at least 1 in 4000 live births in
      the neonatal period. Since hypoxia-inducible factor (HIF)-1alpha can modulate
      ischemic injury via induction of target genes that may protect cells against
      ischemia, and is induced after preconditioning by hypoxia in the neonatal rat
      brain hypoxia-ischemia model, we evaluated whether HIF-1alpha is induced after
      focal ischemia-reperfusion, a model for neonatal stroke. We developed an ischemia
      reperfusion model in postnatal day 10 (P10) rats by transiently occluding the
      middle cerebral artery (MCA) for 1.5 h. The MCA territory was reperfused for 0,
      4, 8, or 24 h and the expression of HIF-1alpha and its target gene, vascular
      endothelial growth factor (VEGF), were delineated. HIF-1alpha protein and VEGF
      protein peaked at 8 h, and declined subsequently at 24 h in injured cortex
      following 1.5 h of MCA occlusion. Double-immunolabeling indicated that both HIF
      1alpha and VEGF are expressed together in neurons with a similar time course of
      expression. The presence of HIF-1alpha and VEGF after moderate ischemia
      reperfusion injury suggests potential avenues to exploit for neuroprotection.

PMID- 14678769
TI  - Adeno-associated viral vector gene expression in the adult rat spinal cord
      following remote vector delivery.
AB  - The current investigation tests whether adeno-associated viral vectors (rAAV)
      undergo remote delivery to the spinal cord via peripheral nerve injection as
      previously demonstrated with adenoviral vectors. The sciatic nerves of adult rats
      (n = 10) were injected with either an rAAV (rAAVCMV-lacZ) or adenoviral (AdCMV
      lacZ) vector (1.4 x 10(7) particles/ml). After 21 days, the rAAV group
      demonstrated significantly higher spinal cord viral expression than the
      adenoviral group (P < 0.024). A second group of rats was injected with rAAV
      expressing the green fluorescence protein (GFP) reporter gene. GFP was detected
      21 days after unilateral sciatic nerve injection in the neurons of the dorsal
      root ganglion and spinal cord. The codistribution of the viral genome and
      transgene in CNS neurons was confirmed with in situ hybridization. In summary,
      rAAV genes are expressed in CNS neurons following peripheral nerve injection at
      levels exceeding those seen following remote adenovirus injection.

PMID- 14678770
TI  - Elevated GDNF levels following viral vector-mediated gene transfer can increase
      neuronal death after stroke in rats.
AB  - Previous studies have indicated that administration of glial cell line-derived
      neurotrophic factor (GDNF) counteracts neuronal death after stroke. However, in
      these studies damage was evaluated at most a few days after the insult. Here, we
      have explored the long-term consequences of two routes of GDNF delivery to the
      rat striatum prior to stroke induced by 30 min of middle cerebral artery
      occlusion (MCAO): striatal transduction with a recombinant lentiviral vector or
      transduction of the substantia nigra with a recombinant adeno-associated viral
      vector and subsequent anterograde transport of GDNF to striatum. Despite high
      GDNF levels, stereological quantification of striatal neuron numbers revealed no
      protection at 5 or 8 weeks after MCAO. In fact, anterograde GDNF delivery
      exacerbated neuronal loss. Moreover, supply of GDNF did not alleviate the
      striatum-related behavioral deficits. Thus, we demonstrate that the actions of
      GDNF after stroke are more complex than previously believed and that high levels
      of this factor, which are neuroprotective in models of Parkinson's disease, can
      increase ischemic damage. Our findings also underscore the need for quantitative
      assessment of long-term neuronal survival and behavioral changes to evaluate the
      therapeutic potential of factors such as GDNF.

PMID- 14678771
TI  - Atypical role of proximal caspase-8 in truncated Tau-induced neurite regression
      and neuronal cell death.
AB  - Abnormal Tau protein is known to be closely associated with several
      neurodegenerative diseases. Previously, we showed that Tau was cleaved by caspase
      3 to generate the cleavage product lacking the C-terminus (DeltaTau-1) during
      neuronal cell death. Here we characterized caspase-8-dependent neurotoxicity of
      the truncated Tau. Introduction of DeltaTau-1 into primary hippocampal neurons
      induced loss of neurites in a caspase-dependent manner. Caspase-8 and -6 were
      proteolytically activated during DeltaTau-1-triggered neuronal cell death, which
      was suppressed by IETD-fmk, caspase-8 inhibitor. Direct targeting of caspase-8
      and its associated FADD with antisense approaches and transient expression of
      their dominant-negative mutants reduced DeltaTau-1-induced apopotosis. Cells
      deficient in caspase-8, but not caspase-3, became sensitized to DeltaTau-1
      mediated toxicity upon reconstitution with caspase-8. In addition, ectopic
      expression of mitochondrial antiapoptotic Bcl-2, Bcl-X(L), or inactive caspase-9
      short form suppressed DeltaTau-1 toxicity. These results suggest that the
      truncated Tau protein activates proximal caspase-8 through FADD as a necessary
      step leading to neuronal cell death and neurite regression, contributing to the
      progression of abnormal Tau-associated neurodegeneracy.

PMID- 14678772
TI  - A slowly formed transient conformer of Abeta(1-40) is toxic to inward channels of
      dissociated hippocampal and cortical neurons of rats.
AB  - The mechanism by which amyloid peptide (Abeta(1-40)) produces effects on
      neurotransmission is currently unresolved. In initial experiments, using the
      patch-clamp technique, we found that 11.5 microM of preaggregated Abeta(1-40)
      altered the hippocampal neuron resting membrane potential and inhibited action
      potential firing. To identify the toxic species, the effects of Abeta(1-40) on
      sodium (I(Na)), calcium (I(Ca)), and potassium (I(K)) currents in hippocampal
      neurons were examined as a function of peptide aggregation state in a specially
      designed miniature recording chamber. Aggregation reactions were induced by
      constant shaking, starting with 50 microM monomeric peptide. At 10- to 30-min
      intervals, the ionic currents were examined on a single neuron suspended in
      control saline and then in a 100-microl sample of the aggregating peptide. We
      found that samples of the peptide taken 60-120 min into the aggregation process
      contained species that exhibited maximal inhibitory effects over a broad
      potential range in the rank ordering of I(Na) > I(Ca). I(K) was inhibited only
      slightly at depolarized potentials. Inhibition of APF through blockade of these
      channels would inhibit normal neuronal activity and directly contribute to
      cognitive dysfunction. In previous studies on SH-EP cells, we showed that neither
      monomeric nor fibrillar peptide had significant effect on cell viability except
      during exposure to the 60-120 minute aggregation product when cell death was
      recorded. Our kinetic model demonstrated that the toxic species was a slowly
      formed transient conformer (activated monomer), which was the only aggregating
      species that passed through a maximum concentration during aggregation. This
      species amounted to only a small fraction of the total amount of aggregating
      peptide. We conclude that, for both the native neurons in the present study as
      well as SH-EP1 cells, the activated monomeric conformer of the peptide is the
      toxic species.

PMID- 14678773
TI  - Neuropeptide alterations in the hippocampal formation and cortex of transgenic
      mice overexpressing beta-amyloid precursor protein (APP) with the Swedish double
      mutation (APP23).
AB  - The role of neuropeptides and the significance of peptidergic mechanisms in
      neurodegenerative diseases are still unclear. In the periphery, nerve injury
      results in dramatic changes in the expression of neuropeptides. An important
      question regards to what extent similar changes occur, and similar mechanisms
      operate, after lesions and/or degeneration in the brain. The purpose of this work
      is, therefore, to study neuropeptides with regard to their presence and
      distribution in the APP23 mouse (HuAPP(751) K670M/N671L under the murine Thy-1
      promoter), a model for Alzheimer's disease, or cerebral amyloidosis, using the
      immunohistochemical technique. In addition, tyrosine hydroxylase and
      acetylcholinesterase were analyzed. This study shows marked neuropeptide changes
      in the hippocampal formation and the ventral cortex, whereas the dorsolateral
      neocortex was less affected. There was a considerable variation with regard to
      peptide expression among animals of the same age which was related to the
      variation in Abeta deposition. Dystrophic and varicose fibers containing galanin,
      neuropeptide Y, enkephalin, and especially cholecystokinin were commonly seen in
      close proximity to amyloid plaques. In addition, generalized changes were
      observed, such as increases of enkephalin and neuropeptide Y in stratum lacunosum
      moleculare and of neuropeptide Y, enkephalin, and dynorphin in mossy fibers. In
      contrast, cholecystokinin was decreased in mossy fibers. Comparatively small
      differences were observed between wild-type and transgenic mice with regard to
      tyrosine hydroxylase (noradrenergic but also dopaminergic fibers) and
      acetylcholine esterase (mainly cholinergic fibers). The increase of neuropeptides
      in dystrophic fibers in this model may represent a response to nerve injury
      caused by the amyloid accumulation and may reflect attempts to counteract
      degeneration by initiating protective and/or regenerative processes.

PMID- 14678774
TI  - Toxicity of glucosylsphingosine (glucopsychosine) to cultured neuronal cells: a
      model system for assessing neuronal damage in Gaucher disease type 2 and 3.
AB  - Patients with Gaucher disease have been classified as type 1 nonneuronopathic,
      type 2 acute neuronopathic, and type 3 chronic neuronopathic phenotypes.
      Increased quantities of glucocerebroside and glucosylsphingosine
      (glucopsychosine) are present in the brain of type 2 and type 3 Gaucher patients.
      Galactosylsphingosine has previously been shown to be neurotoxic in globoid cell
      leukodystrophy (Krabbe disease). To determine whether glucosylsphingosine is also
      neurotoxic, we examined its effect on cultured cholinergic neuron-like LA-N-2
      cells. When these cells were exposed to 1, 5, or 10 microM glucosylsphingosine
      for a period of 18 h, they became shriveled, neurite outgrowth was suppressed,
      and the activities of the lysosomal enzymes glucocerebrosidase, sphingomyelinase,
      and beta-galactosidase were reduced in a dose-dependent manner. Acetylcholine in
      cells exposed to glucosylsphingosine also declined. Cells switched to
      glucosylsphingosine-free medium partially recovered. The data suggest that
      accumulation of glucosylsphingosine contributes to neuronal dysfunction and
      destruction in patients with neuronopathic Gaucher disease.

PMID- 14678775
TI  - Immunohistochemical changes induced by repeated footshock stress: revelations of
      gender-based differences.
AB  - As a growing literature has proven, adverse experiences, particularly when severe
      and persistent, play a pivotal role in the development of neuronal dysfunctions
      and psychopathology. In the present study, the neurochemical changes induced by
      acute and repeated footshock exposure were investigated at the molecular and
      cellular level, using c-fos and phospho-ERK1/2 immunoreactivity and gene
      expression arrays. Marked gender-related differences were found following both
      acute and prolonged footshock exposure. Acute aversive conditioning resulted in
      significant immunohistochemical changes that might be critically involved in the
      modulation of fear-related responses, especially in males. Prolonged footshock
      exposure, on the contrary, was associated with sustained hypothalamic-pituitary
      adrenal axis hyperactivity, differential gender-related patterns of cortical
      limbic activity, and abnormal neuronal plasticity, especially in medial
      prefrontocortical regions. These data may provide additional insights into the
      understanding of the neural circuits underlying the effects of acute and repeated
      footshock exposure as well as clarify some of the mechanisms involved in the
      development of stress-related neuronal abnormalities.

PMID- 14678776
TI  - Hereditary cerebral hemorrhage with amyloidosis Dutch type (AbetaPP 693):
      decreased plasma amyloid-beta 42 concentration.
AB  - Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) is a rare
      autosomal dominant disorder caused by an amyloid-beta precursor protein (AbetaPP)
      693 mutation that clinically leads to recurrent hemorrhagic strokes and dementia.
      The disease is pathologically characterised by the deposition of Abeta in
      cerebral blood vessels and as plaques in the brain parenchyma. This study
      measured the Abeta40 and Abeta42 concentration in plasma of Dutch AbetaPP693
      mutation carriers and controls. We found that the Abeta40 concentration was not
      different between AbetaPP693 mutation carriers and controls. However, the Abeta42
      concentration was significantly decreased in the mutation carriers. No
      correlation exists between the APOE(epsilon)4 allele and the plasma of Abeta40
      and Abeta42 levels in HCHWA-D patients. This finding contrasted with the
      increased concentrations found in Alzheimer's disease. Therefore it is suggested
      that the Dutch AbetaPP693 mutation located within the Abeta coding region of the
      AbetaPP gene has a different effect not only on clinical and pathological
      expression but also on Abeta processing.

PMID- 14678777
TI  - Complex alteration of NMDA receptors in transgenic Huntington's disease mouse
      brain: analysis of mRNA and protein expression, plasma membrane association,
      interacting proteins, and phosphorylation.
AB  - We analyzed NMDA receptor subunit mRNAs, proteins, and anchoring proteins in mice
      transgenic for exon 1 of the HD gene. R6/2 mice had decreased levels of mRNAs
      encoding epsilon1 and epsilon2 NMDA receptor subunits (mouse orthologs of rat
      NR2A and NR2B subunits), but not the zeta1 subunit (mouse ortholog of NR1), as
      assessed by gene expression profiling and Northern blotting. In situ
      hybridization resolved mRNA decreases spatially to the CA1 field of hippocampus.
      Western blotting revealed decreases in plasma membrane-associated epsilon1 and
      epsilon2 subunits in hippocampus, and decreases in plasma membrane-associated
      zeta1 subunit in cortex and hippocampus. In addition, PSD-95 and alpha-actinin-2,
      proteins essential for anchoring NMDA receptors, were decreased. Finally, we
      found a decreased level of tyrosine-phosphorylated epsilon1 subunit, another
      determinant of NMDA receptor trafficking, in R6/2 hippocampus. Taken together,
      these data demonstrate multiple levels of NMDA receptor dysregulation, including
      abnormalities in mRNA expression levels, receptor stoichiometry, protein
      phosphorylation, and receptor trafficking.

PMID- 14678778
TI  - ALDH1 mRNA: presence in human dopamine neurons and decreases in substantia nigra
      in Parkinson's disease and in the ventral tegmental area in schizophrenia.
AB  - Dopamine (DA) neurons degenerate in Parkinson's disease and dopamine
      neurotransmission may be affected in psychotic states seen in schizophrenia.
      Understanding the regulation of enzymes involved in DA metabolism may therefore
      lead to new treatment strategies for these severe conditions. We investigated
      mRNA expression of the cytosolic aldehyde dehydrogenase (ALDH1), presumably
      involved in DA degradation, by in situ hybridization in DA neurons of human
      postmortem material. Parallel labeling for GAPDH, neuron-specific enolase,
      tyrosine hydroxylase, dopamine transporter, and dopamine beta-hydroxylase was
      used to ensure suitability of tissue specimen and to identify all dopamine
      neurons. ALDH1 was found to be expressed highly and specifically in DA cells of
      both substantia nigra (SN) and the ventral tegmental area (VTA) of controls. A
      marked reduction of ALDH1 expression was seen in surviving neurons of SN pars
      compacta but not of those in the VTA in Parkinson's disease. In patients
      suffering from schizophrenia we found ALDH1 expression at normal levels in DA
      cells of SN but at significantly reduced levels in those of the VTA. We conclude
      that ALDH1 is strongly and specifically expressed in human mesencephalic dopamine
      neurons and that low levels of ALDH1 expression correlate with DA neuron
      dysfunction in the two investigated human conditions.

PMID- 14678779
TI  - Oxidative stress mediates toxicity of pyridoxal isonicotinoyl hydrazone analogs.
AB  - Pyridoxal isonicotinoyl hydrazone (PIH) and many of its analogs are effective
      iron chelators in vivo and in vitro, and are of interest for the treatment of
      secondary iron overload. Because previous work has implicated the Fe(3+)-chelator
      complexes as a determinant of toxicity, the role of iron-based oxidative stress
      in the toxicity of PIH analogs was assessed. The Fe(3+) complexes of PIH analogs
      were reduced by K562 cells and the physiological reductant, ascorbate. Depletion
      of the antioxidant, glutathione, sensitized Jurkat T lymphocytes to the toxicity
      of PIH analogs and their Fe(3+) complexes, and toxicity of the chelators
      increased with oxygen tension. Fe(3+) complexes of pyridoxal benzoyl hydrazone
      (PBH) and salicyloyl isonicotinoyl hydrazone (SIH) caused lipid peroxidation and
      toxicity in K562 cells loaded with eicosapentenoic acid (EPA), a readily oxidized
      fatty acid, whereas Fe(PIH)(2) did not. The lipophilic antioxidant, vitamin E,
      completely prevented both the toxicity and lipid peroxidation caused by
      Fe(PBH)(2) in EPA-loaded cells, indicating a causal relationship between
      oxidative stress and toxicity. PBH also caused concomitant lipid peroxidation and
      toxicity in EPA-loaded cells, both of which were reversed as its concentration
      increased. In contrast, PIH was inactive, while SIH was equally toxic toward
      control and EPA-loaded cells, without causing lipid peroxidation, indicating a
      much smaller contribution of oxidative stress to the mechanism of toxicity of
      these analogs. In summary, PIH analogs and their Fe(3+) complexes are redox
      active in the intracellular environment. The contribution of oxidative stress to
      the overall mechanism of toxicity varies across the series.

PMID- 14678780
TI  - Group IB phospholipase A2 from Pseudonaja textilis.
AB  - Pseudonaja textilis, an Australian Elapid, is known to produce a highly toxic
      venom. Both protein profiling and N-terminal sequence analysis showed the
      presence of four new phospholipases A(2) in this venom. Besides being non-lethal,
      the phospholipase A(2) proteins were found to be moderately active enzymes and
      they showed procoagulant property. cDNA cloning and characterization indicated
      the presence of two isoforms of PLA(2) proteins in a single snake, each
      containing the "pancreatic loop," characteristic of group IB phospholipase A(2).
      The genomic cloning also confirmed the presence of two genes each containing four
      exons that are interrupted by three introns. Phylogenetic analysis showed that
      the venom group IB PLA(2) gene is primitive and could have evolved from the same
      ancestor as the mammalian and venom group IA PLA(2) genes. In the present study,
      we report that the Pt-PLA2 gene could be responsible for the production of PL1,
      2, and 3 possibly via RNA editing process.

PMID- 14678781
TI  - Alternative splicing of the human MUC2 gene.
AB  - Human colon cancers differ in amounts of MUC2 mucin synthesized. However, it is
      unclear whether MUC2 encodes a single protein. When clones of human colon cancer
      cells were assayed with antibodies against the TR2 mucin repeat or non-TR2
      epitopes, differences in relative expression of MUC2 proteins suggested multiple
      immunoreactive forms. RT-PCR analysis detected the established 15kbp MUC2 cDNA
      and a novel form (designated MUC2.1) lacking the MUC2 TR2 repeat. Sequencing of
      cDNA and genomic DNA indicated that MUC2.1 results from an alternate splice
      donor. RT-PCR with splice-junction spanning primers confirmed the expression of
      MUC2.1 mRNA. Anti-MUC2.1 antibody stained colon cancer cells and normal colon in
      a pattern different from TR2-specific antibody. The presence of MUC2.1 mucin may
      help us to explain previous conflicting reports that have attempted to correlate
      the relative abundance of MUC2 protein and/or mRNA with the biological behavior
      of colon cancer cells.

PMID- 14678782
TI  - Mass spectrometric analysis of expression of ATPase subunits encoded by
      duplicated genes in the 19S regulatory particle of rice 26S proteasome.
AB  - The 26S proteasome consisting of a 20S proteasome and a pair of 19S regulatory
      particles (RP) plays important roles in degradation of the ubiquitinated protein
      in eukaryotic cells. The RP consists of six different ATPase subunits and, at
      least, 11 non-ATPase subunits. In rice, we previously identified duplicated genes
      encoding four ATPase subunits, OsRpt1, OsRpt2, OsRpt4, and OsRpt5. In this study,
      the genomic sequences of all rice ATPase subunits were identified from the rice
      genome database and the genomic structure of ATPase subunit genes was determined.
      The rice RP was purified, and the ATPase subunit isoforms encoded by three pairs
      of duplicated genes, OsRpt2a/OsRpt2b, OsRpt4a/OsRpt4b, and OsRpt5a/OsRpt5b, were
      identified in RP by using electrospray ionization quadrupole time-of-flight mass
      spectrometry. The relative amounts and the expression patterns of these ATPase
      subunit isoforms in the bran were found to be different from those of the callus,
      suggesting the presence of multiform 19S regulatory particles engaged in the
      tissue-specific protein metabolism.

PMID- 14678783
TI  - Purification, tandem mass characterization, and inhibition studies of
      oxidosqualene-lanosterol cyclase enzyme from bovine liver.
AB  - The oxidosqualene-lanosterol cyclase (OSC) from bovine liver has been isolated
      from the microsomal membrane fraction and purified to homogeneity by
      ultracentrifugation, Q-Sepharose, hydroxyapatite, and HiTrap heparin
      chromatographies. The purified protein required Triton X-100 to retain its
      highest activity. The cyclase had a molecular mass of approximately 70 and
      approximately 140 kDa, as evidenced by a single protein band on silver-stained
      SDS-PAGE and Coomassie-stained PAGE, respectively. Results from Edman degradation
      of OSC suggested that it might have a blocked N-terminus. Further peptide mapping
      coupled with tandem mass spectrometric determination identified three peptide
      fragments, ILGVGPDDPDLVR, LSAEEGPLVQSLR, and NPDGGFATYETK, which are highly
      homologous to human, rat, and mouse OSCs. The purified cyclase showed pH and
      temperature optima at pH 7.4 and 37 degrees C, respectively. The apparent K(M)
      and k(cat)/K(M) values were estimated to be 11 microM and 1.45 mM(-1)min(-1),
      respectively. Inhibition studies using both Ro48-8071 and N-(4
      methylenebenzophenonyl)pyridinium bromide showed potent inhibition of OSC with an
      IC(50) of 11 nM and 0.79 microM, respectively. Results from DTNB modification and
      DTNB coupled with Ro48-8071 competition study suggest that two sulfhydryl groups
      are involved in the catalysis but not located in the substrate binding pocket or
      catalytic active site. The purified OSC was maximally inactivated by diethyl
      pyrocarbonate near neutral pH and re-activated by hydroxylamine, indicating the
      modification of histidine residues. The stoichiometry of histidine modification
      and the extent of inactivation showed that two essential histidine residues per
      active site are necessary for complete bovine liver OSC activity.

PMID- 14678784
TI  - Antioxidants effectively prevent oxidation-induced protein damage in OLN 93
      cells.
AB  - Oxidative stress is supposed to play an important role in demyelinating diseases.
      Oligodendrocytes are the myelin-forming cells in the brain and are highly
      susceptible to oxidative stress due to their low antioxidative defense systems
      and high metabolic rate. In the present work, we tested the response of the
      oligodendrocyte cell line OLN 93 to oxidative stress. OLN 93 cell cultures are
      characterized by a loss of cell viability after oxidation. This loss of cell
      viability is accompanied by an increase in protein oxidation and consequently an
      elevated overall proteolysis. To minimize the oxidative damage, we tested the
      effects of the antioxidants alpha-lipoic acid and coenzyme Q(10). Both compounds
      were able to elevate cell viability and to decrease intracellular protein
      turnover and oxidant induced protein oxidation. Therefore, we concluded that the
      excessive oxidative damage of oligodendrocytes and their protein pool can be
      prevented by the usage of antioxidants.

PMID- 14678785
TI  - Serotonin metabolism in rat skin: characterization by liquid chromatography-mass
      spectrometry.
AB  - We have recently uncovered the full expression of novel cutaneous serotoninergic
      and melatoninergic systems in the human and hamster skin. In this work, we have
      characterized serotonin metabolism in the rat skin using liquid chromatography
      mass spectrometry and found that serotonin undergoes acetylation in the presence
      of acetyl coenzyme A. Inhibition of serotonin acetylation with Cole bisubstrate
      inhibitor shows that rat skin expresses both arylalkylamine and arylamine N
      acetyltransferase activities. The serotonin degradation product-5-hydroxyindole
      acetic acid is also detected and pargyline (monoaminooxidase inhibitor)
      suppresses almost completely 5-hydroxyindole acetic acid accumulation. Together
      with previous data, the present study clearly demonstrates that biotransformation
      of serotonin in mammalian skin follows two alternate pathways. In the first
      pathway, serotonin is acetylated by arylalkylamine and arylamine N
      acetyltransferases to generate the precursor of melatonin. Alternately, serotonin
      may undergo oxidative deamination by monoaminooxidase followed by enzymatic
      degradation by aldehyde dehydrogenase into 5-hydroxyindole acetic acid, which is
      presumably devoid of biological activity. Thus, the current methodological
      development of a liquid chromatography-mass spectrometry-based assay allows rapid
      resolution of the cutaneous metabolism of serotonin.

PMID- 14678786
TI  - Altered proteasome function and subunit composition in aged muscle.
AB  - Myofibrillar protein degradation is mediated through the ubiquitin-proteasome
      pathway. To investigate if altered proteasome activity plays a role in age
      related muscle atrophy, we examined muscle size and proteasome function in young
      and aged F344BN rats. Significant age-related muscle atrophy was confirmed by the
      38% decrease in cross-sectional area of type 1 fibers in soleus muscle.
      Determination of proteasome function showed hydrolysis of fluorogenic peptides
      was equivalent between ages. However, when accounting for the 3-fold increase in
      content of the 20S catalytic core in aged muscle, the lower specific activity
      suggests a functional loss in individual proteins with aging. Comparing the
      composition of the catalytic beta-subunits showed an age-related 4-fold increase
      in the cytokine-inducible subunits, LMP2 and LMP7. Additionally, the content of
      the activating complexes, PA28 and PA700, relative to the 20S proteasome was
      reduced 50%. These results suggest significant alterations in the intrinsic
      activity, the percentage of immunoproteasome, and the regulation of the 20S
      proteasome by PA28 and PA700 in aged muscle.

PMID- 14678787
TI  - Inversion of the allosteric response of Escherichia coli glucosamine-6-P
      deaminase to N-acetylglucosamine 6-P, by single amino acid replacements.
AB  - Amino acid replacements in the active site of glucosamine-6-P deaminase from
      Escherichia coli (GlcN6P deaminase, EC 3.5.99.6) involving the residues D141 and
      E148 produce atypical allosteric kinetics. These residues are located in the
      chain segment 139-156 which is part of the active site and which also forms
      several intersubunit contacts close to the allosteric site. In the D141N and
      E148Q mutant forms of this deaminase, there is an inversion of the effect of its
      physiological allosteric effector, N-acetylglucosamine 6-P, which becomes an
      inhibitor at substrate concentrations above a critical value. For both mutants,
      this particular point appears at low substrate concentration and the inhibition
      by the allosteric activator is the dominant effect in velocity versus substrate
      curves. These effects are analyzed as a particular case of the concerted
      allosteric model, assuming that the R state, the conformer displaying the higher
      affinity for the substrate, is the less catalytic state, thus producing an
      inverted allosteric response.

PMID- 14678788
TI  - S-methylmethionine is both a substrate and an inactivator of 1-aminocyclopropane
      1-carboxylate synthase.
AB  - S-methyl-L-methionine (SMM) is ubiquitous in the tissues of flowering plants, but
      its precise function remains unknown. It is both a substrate and an inhibitor of
      the pyridoxal 5(')-phosphate-dependent enzyme 1-aminocyclopropane-1-carboxylate
      (ACC) synthase, due to its structural similarity to the natural substrate of this
      enzyme, S-adenosyl-L-methionine. In the reaction with ACC synthase, SMM can
      either be transaminated to yield 4-dimethylsulfonium-2-oxobutyrate; converted to
      alpha-ketobutyrate, ammonia, and dimethylsulfide; or inactivate the enzyme
      covalently after elimination of dimethylsulfide. These results suggest a
      previously unrecognized role for SMM in the regulation of ACC synthase activity
      in plants.

PMID- 14678789
TI  - Single nucleotide polymorphism analysis and functional characterization of the
      human Ah receptor (AhR) gene promoter.
AB  - The aryl hydrocarbon receptor (AhR) mediates biological and toxicological actions
      of e.g., halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p
      dioxin. Although much is known about the biochemical and molecular mechanisms of
      AhR action, little is known about the control of the expression of the AhR gene
      itself. Therefore, we aimed at the identification and characterization of regions
      important for constitutive AhR gene expression. First, we screened 2.6 kb of the
      5(')-flanking region of the AhR gene in 91 healthy Caucasian volunteers for
      naturally occurring genetic variants. Seven variants were detected. However, they
      do not seem to influence AhR gene expression in lymphocytes. Using a 2.7 kb AhR
      promoter luciferase reporter gene construct and various deletion constructs, a
      putative regulatory region was identified and characterized further by
      electrophoretic mobility shift assays and site-directed mutagenesis. These
      investigations were confirmed by cotransfection experiments in Drosophila SL2
      cells. The obtained results prove an involvement of Sp1 in AhR gene regulation.

PMID- 14678790
TI  - Cytochrome c: a catalyst and target of nitrite-hydrogen peroxide-dependent
      protein nitration.
AB  - Nitration of protein tyrosine residues to 3-nitrotyrosine (NO2Tyr) serves as both
      a marker and mediator of pathogenic reactions of nitric oxide (*NO), with
      peroxynitrite (ONOO-) and leukocyte peroxidase-derived nitrogen dioxide (*NO2)
      being proximal mediators of nitration reactions in vivo. Cytochrome c is a
      respiratory and apoptotic signaling heme protein localized exofacially on the
      inner mitochondrial membrane. We report herein a novel function for cytochrome c
      as a catalyst for nitrite (NO2-) and hydrogen peroxide (H2O2)-mediated nitration
      reactions. Cytochrome c catalyzes both self- and adjacent-molecule
      (hydroxyphenylacetic acid, Mn-superoxide dismutase) nitration via heme-dependent
      mechanisms involving tyrosyl radical and *NO2 production, as for phagocyte
      peroxidases. Although low molecular weight phenolic nitration yields were similar
      for cytochrome c and the proteolytic fragment of cytochrome c microperoxidase-11
      (MPx-11), greater extents of protein nitration occurred when MPx-11 served as
      catalyst. Partial proteolysis of cytochrome c increased both the peroxidase and
      nitrating activities of cytochrome c. Extensive tyrosine nitration of Mn
      superoxide dismutase occurred when exposed to either cytochrome c or MPx-11 in
      the presence of H2O2 and NO2-, with no apparent decrease in catalytic activity.
      These results reveal a post-translational tyrosine modification mechanism that is
      mediated by an abundant hemoprotein present in both mitochondrial and cytosolic
      compartments. The data also infer that the distribution of specific proteins
      capable of serving as potent catalysts of nitration can lend both spatial and
      molecular specificity to biomolecule nitration reactions.

PMID- 14678791
TI  - Different types of glutathionylation of hemoglobin can exist in intact
      erythrocytes.
AB  - Glutathionylation of hemoglobin (Hb) was studied by incubation of intact human
      erythrocytes with 1 mM tert-butylhydroperoxide (tBHP). Electrophoresis of the
      membranes showed a time dependent increase of membrane-bound Hb alpha chain until
      10 min, and immunoblotting study showed that membrane-bound Hb alpha chain
      reacted with anti-glutathione antibody only after 10 min. Concomitant with the Hb
      alpha chain, membrane associated actin, spectrin, and glyceraldehyde 3-phosphate
      dehydrogenase reacted with the antibody. Cytosolic Hb of the control erythrocytes
      reacted with anti-glutathione antibody. Together with our previous paper, the
      present study indicates that at least three different types of glutathionylation
      of Hb can exist in erythrocytes. The first type is a mixed disulfide bond between
      reduced glutathione (GSH) and normal Hb. The second type is a disulfide bond
      between the cysteine 93 of metHb beta chain and oxidized glutathione (GSSG), and
      the third type is a disulfide bond between the other cysteine residues of metHb
      alpha chain and/or metHb beta chain and GSSG.

PMID- 14678792
TI  - Structural studies of a Phe256Trp mutant of human salivary alpha-amylase:
      implications for the role of a conserved water molecule in enzyme activity.
AB  - In the mechanism of hydrolysis of starch by alpha-amylases, a conserved water
      molecule bridging two catalytic residues has been implicated. In human salivary
      alpha-amylase (HSAmy), this water (W641), observed in many alpha-amylase
      structures, is part of a chain of water molecules. To test the hypothesis that
      W641 may be involved in the mechanism, Phe256 in the close vicinity was mutated
      to a Trp residue. X-ray structure of F256W complexed to 2-amino-2-(hydroxyethyl)
      1,3-propanediol at 2.1A revealed that the water chain is disrupted. In the F256W
      structure exhibits a positional shift in His305, characteristic of alpha-amylase
      complex structures. Kinetic analysis, in comparison with HSAmy, revealed that the
      mutant exhibited a 70-fold decrease in the specific activity for starch and
      significantly reduced k(cat) (20-fold) and K(m) (4-fold) for maltoheptaoside.
      Collectively, these results suggest that W641 and the chain of water molecules
      may be critical for the alpha-amylase activity.

PMID- 14678793
TI  - Mucin binding mitogenic lectin from freshwater Indian gastropod Belamyia
      bengalensis: purification and molecular characterization.
AB  - A lectin was purified from the hemolymph of the freshwater Indian gastropod
      Belamyia bengalensis. The purification involved successive ion-exchange
      chromatography on Resource Q and gel filtration on Superose 12 column in FPLC
      system. Homogeneity of the protein was confirmed by polyacrylamide gel
      electrophoresis. Belamyia bengalensis lectin (BBL) was a monomeric protein with a
      molecular weight of 33 kDa as demonstrated by gel filtration and SDS-PAGE. It is
      a glycoprotein containing 6% total sugar and its activity is highly dependent on
      Ca(2+). BBL agglutinated human erythrocytes and is a blood group non-specific
      lectin. It agglutinated animal erythrocytes also. Hapten inhibition studies
      indicated that BBL shows binding specificity only for N-acetyl-D-glucosamine and
      N-acetyl-D-galactosamine at a high concentration among the mono- and
      oligosaccharides tested. Among the glycoproteins used for hemagglutination
      inhibition assay, porcine submaxillary mucin was found to be the best inhibitor.
      Chemical modification studies indicated that Lys, Arg, and Trp are essential for
      the sugar-binding activity of BBL. Circular dichroism spectra revealed high
      content of alpha-helical structure in the lectin. BBL is a potent mitogen as it
      stimulated the T-lymphocyte proliferation, specifically the Th1 subset.

PMID- 14678794
TI  - Kinetic analysis of human homogentisate 1,2-dioxygenase.
AB  - Homogentisate 1,2-dioxygenase (HGD) is a mononuclear Fe(II)-dependent oxygenase
      that catalyzes the third step in the pathway for the catabolism of tyrosine, the
      conversion of homogentisate (HG) to maleylacetoacetate (MAA). We have
      heterologously expressed and purified native human HGD in the apo form. Steady
      state analysis varying the concentration of both HG and molecular oxygen shows
      that the purified enzyme has a turnover number of 16 s(-1). Our data suggest that
      HG binds to the apo-enzyme and that the apo-HGD.HG complex does not bind Fe(II)
      and dissociates slowly at approximately 0.028 s(-1). The rate constant for the
      dissociation of Fe(II) from the holo-enzyme as measured under anaerobic
      conditions is 0.00004 s(-1) and indicates that this process is not relevant in
      steady-state turnover. The addition of HG and molecular oxygen to the holo-enzyme
      is formally random as the holo-enzyme reduces molecular oxygen at a rate of
      1.35x10(3) M(-1) s(-1) at 4 degrees C. The term ordered with respect to the
      addition of substrates is most descriptive as the rate of reduction of molecular
      oxygen must increase in the presence of HG to sustain the observed turnover
      number.

PMID- 14678795
TI  - Six-helix bundle assembly and analysis of the central core of mumps virus fusion
      protein.
AB  - The fusion protein of enveloped viruses mediates the fusion between the viral and
      cellular membranes, allowing the penetration of the viral genomes into the host
      cell. Many of these proteins share a common fold comprising a central core trimer
      of anti-parallel coiled-coil heterodimers, which are formed by two discontinuous
      heptad repeat (HR) motifs located at the ectodomain of the fusion proteins. In
      this study, we constructed and purified the corresponding regions (HR1 and HR2)
      of mumps virus fusion protein that are predicted to form coiled coil. The HR1 and
      HR2 were expressed and purified separately or as a single chain connected by an
      amino acid linker (HR1-linker-HR2, named 2-Helix). Series of biochemical and
      biophysical analyses of the expressed proteins have shown that HR1 and HR2 of
      mumps virus fusion protein share the common features of other enveloped virus
      fusion proteins. CD spectral results show that HR1 forms an alpha-helical coil
      structure while HR2 exists as an unstructured monomer in PBS in nature. Mixtures
      of HR1 and HR2 could form a stable six-helix bundle, indicating the interaction
      of HR1 and HR2. The 2-Helix protein also shows characteristic properties of the 6
      helix bundle. Therefore, mumps virus fusion protein has a common core
      architecture and its HR regions could be used as a drug target for virus fusion
      inhibitors.

PMID- 14678796
TI  - Cloning, sequence analysis, and purification of choline oxidase from Arthrobacter
      globiformis: a bacterial enzyme involved in osmotic stress tolerance.
AB  - Choline oxidase catalyzes the four-electron oxidation of choline to glycine
      betaine, one of a limited number of compounds that accumulate to high levels in
      the cytoplasm of cells to prevent dehydration and plasmolysis in adverse
      hyperosmotic environments. In the present study, the highly GC rich codA gene
      encoding for choline oxidase was cloned from genomic DNA of Arthrobacter
      globiformis strain ATCC 8010 and expressed to high yields in Escherichia coli
      strain Rosetta(DE3)pLysS. The resulting enzyme was purified to high levels in a
      single chromatographic step using DEAE-Sepharose, as shown by SDS-PAGE analysis.
      Denaturation and mass spectroscopic analyses showed that the covalent linkage
      between the FAD cofactor and the protein is preserved in recombinant choline
      oxidase, consistent with protein flavinylation being a self-catalytic process.
      The enzyme was shown to be a homodimer of 120,000 Da by size-exclusion
      chromatography and to be active with both choline and betaine aldehyde as
      substrate. Sequencing analysis indicated that the nucleotide sequence of codA
      originally reported in GenBank contains seven flaws, resulting in a translated
      protein with a significantly altered amino acid sequence between position 298 and
      410.

PMID- 14678797
TI  - CHMP4b is a major binding partner of the ALG-2-interacting protein Alix among the
      three CHMP4 isoforms.
AB  - The ALG-2-interacting protein Alix has recently been demonstrated to associate
      with CHMP4b that is a human homologue of yeast Snf7p (also named Vps32p) and a
      member of the family of small coiled-coil proteins named CHMP implicated in
      playing roles in multivesicular body sorting. In addition to the previously
      isolated cDNAs for two CHMP4 proteins (CHMP4a and CHMP4b), we isolated a cDNA for
      a new member of the CHMP4 subfamily (designated CHMP4c). Northern blot analyses
      revealed different expression patterns of the mRNAs for the three CHMP4 isoforms
      in human tissues. CHMP4b messages were expressed at higher levels in all 12
      tissues tested in comparison with the CHMP4a and CHMP4c transcripts, particularly
      in heart and skeletal muscle. The interaction with Alix was detected for each
      CHMP4 isoform by co-immunoprecipitation experiments using lysates of HEK293 cells
      expressing each epitope-tagged CHMP4 protein and Alix fused with green
      fluorescent protein. Further, using recombinant glutathione S-transferase (GST)
      fusion protein of truncated Alix (amino acids 1-423) and thioredoxin-tagged CHMP4
      proteins, the direct interactions were detected by a GST pull-down assay, where
      CHMP4b showed a stronger interaction than other CHMP4 isoforms. These results
      suggest that CHMP4b is a major binding partner of Alix among the three CHMP4
      isoforms.

PMID- 14678798
TI  - Properties of a novel periplasmic catalase-peroxidase from Escherichia coli
      O157:H7.
AB  - A subset of catalase-peroxidases are distinguished by their periplasmic location
      and their expression by pathogens. Kinetic and spectral properties have not been
      reported for any of these enzymes. We report the cloning, expression, isolation,
      and characterization of KatP, a periplasmic catalase-peroxidase from Escherichia
      coli O157:H7. Absorption spectra indicated a mixture of heme states dominated by
      the pentacoordinate and hexacoordinate high-spin forms. Apparent k(cat) values
      for catalase (1.8x10(4) s(-1)) and peroxidase (77 s(-1)) activities were greater
      than those of other catalase-peroxidases. However, apparent K(M) values for H2O2
      were also higher (27 mM for catalase and 3 mM for peroxidase). Ferric KatP
      reacted with peracetic acid to form compound I (8.8x10(3) M(-1) s(-1)) and with
      CN(-) to form a ferri-cyano complex (3.9x10(5) M(-1) s(-1)) consistent with other
      catalase-peroxidases. The isolation and characterization of KatP opens new
      avenues to explore mechanisms by which the periplasmic catalase-peroxidases may
      contribute to bacterial virulence.

PMID- 14678799
TI  - A novel form of recessive limb girdle muscular dystrophy with mental retardation
      and abnormal expression of alpha-dystroglycan.
AB  - The limb girdle muscular dystrophies are a heterogeneous group of conditions
      characterized by proximal muscle weakness and disease onset ranging from infancy
      to adulthood. We report here eight patients from seven unrelated families
      affected by a novel and relatively mild form of autosomal recessive limb girdle
      muscular dystrophy (LGMD2) with onset in the first decade of life and
      characterized by severe mental retardation but normal brain imaging.
      Immunocytochemical studies revealed a significant selective reduction of alpha
      dystroglycan expression in the muscle biopsies. Linkage analysis excluded known
      loci for both limb girdle muscular dystrophy and congenital muscular dystrophies
      in the consanguineous families. We consider that this represents a novel form of
      muscular dystrophy with associated brain involvement. The biochemical studies
      suggest that it may belong to the growing number of muscular dystrophies with
      abnormal expression of alpha-dystroglycan.

PMID- 14678800
TI  - Phenotype and sarcoglycan expression in Tunisian LGMD 2C patients sharing the
      same del521-T mutation.
AB  - Limb-girdle muscular dystrophy type 2C is an autosomal recessive muscular
      disorder caused by mutations in the gene encoding the gamma-sarcoglycan subunit.
      This gamma-sarcoglycanopathy is prevalent in Tunisia where only one homozygous
      mutation a 521-T deletion has been identified. The aim of this study was to carry
      out a comparative clinical and immunocytochemical analysis of Tunisian patients
      sharing the same gamma-sarcoglycan gene mutation. One hundred and thirty-two
      patients were classified as severe, moderate or mild according to a calculated
      severity score. Heterogeneous phenotypes between siblings were encountered in 75%
      of the families. The severity of the disease was not found to be related to the
      age of onset. Immunohistochemical studies of muscle biopsy showed a total absence
      of gamma-sarcoglycan, a normal or slightly reduced alpha and delta-sarcoglycans
      whereas the expression of beta-sarcoglycan was variable. The residual sarcoglycan
      expression was not related to the clinical phenotype. In conclusion, the
      phenotypic variability in sarcoglycanopathies in Tunisia seems to involve a
      modifying gene controlling the course of the disease.

PMID- 14678801
TI  - Molecular analysis of LGMD-2B and MM patients: identification of novel DYSF
      mutations and possible founder effect in the Italian population.
AB  - Dysferlin, the protein product of the dysferlin gene (DYSF), has been shown to
      have a role in calcium-induced membrane fusion and repair. Dysferlin is absent or
      drastically reduced in patients with the following autosomal recessive disorders:
      limb-girdle muscular dystrophy type 2B (LGMD-2B), Miyoshi myopathy (MM) and
      distal anterior compartment myopathy. To date, less than 45 mutations have been
      described in DYSF and a wide inter- and intra-familial variation in clinical
      phenotype has been associated with the same mutation. This observation underlines
      the relevance of any new report describing genotype/phenotype correlations in
      dysferlinopathic patient and families. Here we present the results of clinical,
      biochemical and genetic analysis performed on one MM and three LGMD Italian
      families. By screening the entire coding region of DYSF, we identified three
      novel mutations (two missense substitutions and one frame shift microdeletion).
      The possible existence of a founder effect for the Arg959Trp mutation in the
      Italian population is discussed.

PMID- 14678802
TI  - Disruption of dystroglycan axis by beta-dystroglycan processing in
      cardiomyopathic hamster muscle.
AB  - Alpha-dystroglycan is a cell surface peripheral membrane protein which binds to
      the extracellular matrix, while beta-dystroglycan is a type I integral membrane
      protein which anchors alpha-dystroglycan to the cell membrane via the N-terminal
      extracellular domain. The complex composed of alpha- and beta-dystroglycan is
      called the dystroglycan complex. Although defects of the dystroglycan gene have
      not been identified as the primary causes of hereditary diseases in humans,
      secondary but significant abnormalities of the dystroglycan complex have been
      revealed in severe muscular dystrophies, including sarcoglycanopathy (LGMD2C, D,
      E and F). In this study, we investigated proteolytic processing of beta
      dystroglycan and its effect on the extracellular matrix-cell membrane linkage in
      cardiomyopathic hamsters, the model animals of LGMD2F. Compared to normal
      controls, proteolytic processing of beta-dystroglycan was activated in the
      skeletal, cardiac and smooth muscles of cardiomyopathic hamsters and this
      resulted in the partial disruption of the dystroglycan complex in these tissues.
      These phenomena were observed from the early phase of muscle degeneration
      process. Our results suggest that proteolytic processing of beta-dystroglycan
      disrupts the extracellular matrix-cell membrane linkage via the dystroglycan
      complex and this may play a role in the molecular pathogenesis of muscle
      degeneration in cardiomyopathic hamsters.

PMID- 14678803
TI  - The Duchenne muscular dystrophy population in Denmark, 1977-2001: prevalence,
      incidence and survival in relation to the introduction of ventilator use.
AB  - Mechanical ventilation of patients with Duchenne muscular dystrophy continues to
      be a subject of study. The purpose was to estimate prevalence, incidence,
      mortality and use of mechanical ventilation in the total Duchenne muscular
      dystrophy population in Denmark between 1977 and 2001 and further, to reconstruct
      the introduction of mechanical ventilation to assess the role of the patient
      organization. Study objects were collected from five sources and verifiable cases
      identified. Negotiations between health authorities and the patient organization
      constituted main empirical data for the reconstruction. While overall incidence
      remained stable at 2.0 per 10(5), prevalence rose from 3.1 to 5.5 per 10(5),
      mortality fell from 4.7 to 2.6 per 100 years at risk and prevalence of Duchenne
      muscular dystrophy ventilator users rose from 0.9 to 43.4 per 100. We conclude
      that survival of Duchenne muscular dystrophy patients has increased and
      ventilator use is probably a main reason. The patient organization exercised a
      key role but acted upon preconditions created by other players.

PMID- 14678804
TI  - Executive dysfunction and avoidant personality trait in myotonic dystrophy type 1
      (DM-1) and in proximal myotonic myopathy (PROMM/DM-2).
AB  - A previous study in proximal myotonic myopathy (PROMM/DM-2) and myotonic
      dystrophy type 1 (DM-1) using brain positron emission tomography demonstrated a
      reduced cerebral blood flow in the frontal and temporal regions associated with
      cognitive impairment. The objective was to investigate further cognitive and
      behavioural aspects in a new series of patients with DM-1 and PROMM/DM-2.
      Nineteen patients with genetically determined PROMM/DM-2 and 21 patients with
      moderately severe DM-1 underwent neuropsychological testing and neuropsychiatric
      interviews. DM-1 and PROMM/DM-2 patients had significantly lower scores on tests
      of frontal lobe function compared to controls. Neuropsychiatric interviews
      demonstrated an avoidant trait personality disorder in both patient groups. Brain
      single photon emission computed tomography showed frontal and parieto-occipital
      hypoperfusion. The results suggest that there is a specific cognitive and
      behavioural profile in PROMM/DM-2 and in DM-1, and that this profile is
      associated with hypoperfusion in frontal and parieto-occipital regions of the
      brain.

PMID- 14678805
TI  - Relation of CTG expansion and clinical variables to electrocardiogram conduction
      abnormalities and sudden death in patients with myotonic dystrophy.
AB  - We prospectively followed 63 patients with myotonic dystrophy (DM) after
      establishing diagnosis of DM for an average 8 years in an attempt to detect
      conduction disturbances (by electrocardiography and/or Holter monitoring) and
      sudden cardiac events (sudden death, cardiac syncope) and correlate them to
      potential predicting factors (CTG repeat expansion in the myotonin protein kinase
      gene and several clinical variables: clinical type and duration of DM, age and
      sex). Twenty-six patients developed conduction disturbances, five patients died
      suddenly, and two patients experienced cardiac syncope necessitating urgent
      implantation of pacemaker. Analysis showed no significant correlation between
      conduction disturbances and/or cardiac events and CTG expansion. Furthermore, no
      correlation was found with type of DM, whereas conduction disturbances and sudden
      cardiac events correlated with patients' age, duration of disease and male sex.
      Results on our cohort of DM patients show that CTG expansion has no role in
      predicting neither conduction abnormalities nor sudden death. It seems that risk
      of sudden death increases with duration of disease and age, and that risk is
      higher in male patients.

PMID- 14678806
TI  - Hereditary neuropathy with liability to pressure palsies (HNPP) in a toddler
      presenting with toe-walking, pain and stiffness.
AB  - The typical clinical presentation of hereditary neuropathy with liability to
      pressure palsies is an adult-onset recurrent, painless monoparesis.
      Electrophysiological abnormalities--decreased nerve conduction velocities and
      delayed distal latencies--can be detected even in asymptomatic patients. We
      describe a toddler, who presented with asymmetric toe walking, painful cramps and
      stiffness in the legs. He had calf hypertrophy, brisk tendon reflexes and
      bilateral Babinski signs and the electrophysiological examination was normal. The
      unlikely diagnosis of hereditary neuropathy with liability to pressure palsies
      was reached 5 years later, when the boy started to complain of episodic numbness
      and weakness in the upper extremities. His father, paternal aunt and grandmother
      had similar symptoms, but they had never been investigated. The typical 1.5 Mb
      deletion on chromosome 17p11.2-12 was found in our patient and his affected
      relatives.

PMID- 14678807
TI  - A novel homozygous missense mutation in the GNE gene of a patient with quadriceps
      sparing hereditary inclusion body myopathy associated with muscle inflammation.
AB  - An adult-onset hereditary inclusion body myopathy with sparing of the quadriceps
      muscle was originally described in Iranian Jews and assigned to a locus on
      chromosome 9p12-p13. Recently, mutations of the UDP-N-acetylglucosamine-2
      epimerase/N-acetylmannosamine kinase (GNE) gene were reported to cause hereditary
      inclusion body myopathy and one type of distal myopathy in a world-wide
      distribution. Importantly, the lack of muscle inflammation was used to
      distinguish hereditary inclusion body myopathy from the sporadic form of
      inclusion body myopathy. We report a case of a quadriceps-sparing myopathy in a
      non-Jewish, Iranian patient with a high degree of muscle inflammation. A novel
      homozygous G-to-A mutation (128933G-->A) in exon 7 changing a valine to
      isoleucine (V367I) in the epimerase domain of the GNE gene was found. We conclude
      that muscle inflammation is not sufficient to exclude the diagnosis of hereditary
      inclusion body myopathy.

PMID- 14678808
TI  - Thrombosis in children with acute lymphoblastic leukemia: part I. Epidemiology of
      thrombosis in children with acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. With
      the advent of aggressive multimodality therapy, ALL has become a curable disease
      for majority of pediatric patients. Thromboembolism (TE) is a well-recognized
      serious complication in association with ALL leading to significant morbidity. It
      can be potentially fatal in over 50% of the affected patients. Development of TE
      does interfere with the scheduled treatment plan for ALL and, thus, ultimate
      outcome from ALL. Recent evidence indicates that concomitant administration of
      asparaginase and steroids is likely to be associated with higher incidence of TE,
      especially in children with at least one prothrombotic risk factor. In addition,
      older children and patients with high risk ALL may be at higher risk for
      developing TE. However, the epidemiology and the exact pathogenesis of this
      entity have not yet been clearly defined. To reduce the incidence of TE and its
      impact on overall outcome as well as on the quality of life in children
      undergoing treatment for ALL, further studies to define the epidemiology of TE in
      relation to the biology of ALL and chemotherapy protocols are urgently needed.
      The purpose of this review is to evaluate the current knowledge of TE in
      association with ALL in children, especially in relation with the treatment
      protocols and genetic background. This review will be published in three parts.
      The first part will review the available information regarding epidemiology of TE
      in children with ALL.

PMID- 14678809
TI  - The prothrombotic state in atrial fibrillation: the atrium, the endothelium...
      And tissue factor?

PMID- 14678810
TI  - Tissue factor expression in atrial endothelia associated with nonvalvular atrial
      fibrillation: possible involvement in intracardiac thrombogenesis.
AB  - INTRODUCTION: Tissue factor plays a key role in the extrinsic coagulation pathway
      and is induced by inflammatory cytokines. Atrial myocarditis has been detected
      recently in some patients with lone atrial fibrillation. Virchow's triad of low
      blood flow, hypercoagulability, and endothelial dysfunction, enhances thrombus
      formation. The present study was designed to elucidate the role of endothelial
      dysfunction in thrombogenesis associated with nonvalvular atrial fibrillation.
      MATERIAL AND METHODS: We investigated tissue factor expression in the endothelia
      of left atrial appendages obtained from seven patients with nonvalvular atrial
      fibrillation and cardiogenic thromboembolism. Tissues were divided into 7-13
      sections and compared with control specimens from four patients who died of
      noncardiac events. Expression of tissue factor, von Willebrand factor and tissue
      factor pathway inhibitor was evaluated by immunohistochemistry. RESULTS:
      Histopathologically, inflammatory cells infiltrated the endocardium and all seven
      patients showed features of persistent myocarditis. Activated T cells [15.3+/-9.4
      cells/high power field (HPF, mean+/-S.D.) vs. control 2.2+/-4.4/HPF (P=0.0294)]
      and a few macrophages [5.1+/-8.4 cells/HPF vs. control 2.4+/-3.5 cells/HPF
      (P=NS)] infiltrated the endocardium. Tissue factor was overexpressed in the
      endothelia particularly in tissues containing inflammatory cells and denuded
      matrix of the endocardium, compared with the control group. Von Willebrand
      factor, but not tissue factor pathway inhibitor, was also overexpressed in these
      tissues. CONCLUSION: Tissue factor expression induced by local inflammation is
      involved in the pathogenesis of thrombosis in patients with nonvalvular atrial
      fibrillation.

PMID- 14678811
TI  - Increased high molecular weight fibrinogen in pre-eclampsia.
AB  - INTRODUCTION: The major coagulation protein fibrinogen (Fg) is a heterogeneous
      protein with three main fractions: high molecular weight fibrinogen (HMW-Fg), low
      molecular weight fibrinogen (LMW-Fg) and low molecular weight' fibrinogen. The
      clottability of high molecular weight fibrinogen is highest as compared to the
      other fractions. Pre-eclampsia is associated with a state of hypercoagulability,
      and with an increase of fibrinogen concentration. The aim of the present study
      was to examine if the increased total fibrinogen plasma concentration in patients
      with pre-eclampsia is associated with a change in distribution of the main
      fibrinogen fractions. MATERIAL AND METHODS: Plasma was collected from 14 patients
      with pre-eclampsia and from 14 healthy pregnant matched controls. Total
      fibrinogen concentrations were determined according to Clauss. The percentage
      high molecular weight fibrinogen was assessed by SDS-electrophoresis and
      densitometry after isolation of fibrinogen by precipitation. The study groups
      were compared by the Mann-Whitney U-test. RESULTS: The median (range) total
      fibrinogen concentration in the pre-eclampsia group was 5.04 (3.25-6.51) g/l and
      in the control group 4.19 (3.61-5.38) g/l (p<0.05). The median (range) percentage
      high molecular weight fibrinogen was 76.5 (69.6-84.0)% and 73.0 (69.0-78.9)% in
      the pre-eclampsia and control group, respectively (p<0.05). CONCLUSIONS: In pre
      eclampsia, the concentration of total fibrinogen is increased and the percentage
      high molecular weight fibrinogen is also slightly higher than in normal
      pregnancy. These results may be a reflection of the exaggerated inflammatory
      response, and subsequent endothelial activation, which are currently believed to
      be the key pathophysiological mechanisms in pre-eclampsia.

PMID- 14678812
TI  - A new rapid bedside assay for quantitative testing of D-Dimer (Cardiac D-Dimer)
      in the diagnostic work-up for deep vein thrombosis.
AB  - The accuracy of a new bedside, rapid and quantitative D-Dimer assay (Cardiac D
      Dimer) was evaluated in outpatients with clinically suspected deep vein
      thrombosis (DVT); VIDAS test was used as reference method. Eighty consecutive
      outpatients with suspected DVT of a lower limb were included in the study.
      Patients were classified as DVT positive or negative according to results of
      objective test (serial CUS), pretest clinical probability and 3-month follow-up.
      DVT was diagnosed in 32/80 patients (40%). The performance of the two D-Dimer
      assays was comparable, as indicated by the areas under the ROC curves (0.89 and
      0.88, for Cardiac D-Dimer and VIDAS, respectively) and the coefficient of
      correlation (r=0.91). The reproducibility of the test was acceptable (from 6.2%
      to 12.0%). The sensitivity and negative predictive values were 100% for both
      tests. The specificity (SP) and positive predictive values (PPV) were similar
      (SP: 50.0% and 52.0%, PPV: 57.1% and 58.2%, for Cardiac D-Dimer and VIDAS,
      respectively). The Cardiac D-Dimer test proved to be very accurate and produced
      results fully comparable to those obtained with the VIDAS test. Since the test
      can be directly performed in the emergency room within a few minutes, it seems to
      have great clinical potential. The place of this assay in the diagnostic strategy
      of DVT remains to be determined in prospective management studies.

PMID- 14678813
TI  - Can causes of false-normal D-dimer test [SimpliRED] results be identified?
AB  - BACKGROUND: To simplify the diagnostic strategy of patients suspected for venous
      thromboembolism, the use of D-dimer tests has been advocated. Very important for
      the safety of such diagnostic strategies would be the capacity to recognise false
      normal D-dimer results, in order to prevent inadequately withholding
      anticoagulant treatment in patients who actually have the disease. Insight in the
      causes of false-normal D-dimer results would therefore be necessary. We
      hypothesised that certain patient characteristics are associated with relatively
      low plasma D-dimer levels and, therefore, could increase the risk of false-normal
      results. METHODS: Consecutive patients with an objectively confirmed venous
      thromboembolic event and an independently obtained false-normal SimpliRED D-dimer
      test result were included in the study. For each patient, two controls with
      objectively confirmed venous thromboembolism and an adequate abnormal D-dimer
      result were selected. Baseline patient characteristics, obtained by standardised
      questionnaires, were compared between the two groups of patients. RESULTS: In
      total, 686 patients had a venous thromboembolic event and 47 of these patients
      had a false-normal SimpliRED result. Therefore, the overall sensitivity of the
      SimpliRED test for venous thromboembolism was 94% (95% CI: 92-95%). Although the
      prevalence of certain clinical characteristics was significantly higher in
      patients with a false-normal D-dimer result than in the controls [odds ratios for
      (LMW)heparin treatment and symptoms lasting more than 10 days: 5.1 (95% CI: 1.5
      18.7) and 3.2 (95% CI:1.4-7.4), respectively], the prevalence of these
      characteristics was also high in the control group with an adequate abnormal D
      dimer. Combining two or more of these characteristics had a low prevalence and
      did not further improve the ability to identify those patients with a false
      normal D-dimer test at presentation. CONCLUSIONS: Although these findings clearly
      indicate an association between certain baseline clinical characteristics and the
      occurrence of a false-normal SimpliRED test, the clinical utility for these
      characteristics is limited.

PMID- 14678814
TI  - Comparison of turbidimetric aggregation and in vitro bleeding time (PFA-100) for
      monitoring the platelet inhibitory profile of antiplatelet agents in patients
      undergoing stent implantation.
AB  - The present study compared classical ADP-induced platelet aggregation vs. PFA-100
      closure times using collagen/ADP membrane cartridges to monitor the degree of
      platelet-inhibiting effect of three drug regimens: ticlopidin,
      abciximab/ticlopidin and loading dose clopidogrel, each on top of aspirin
      (acetylsalicylic acid, ASA) during and after elective stent placement
      (intervention) in a total of 31 patients with acute coronary syndrome. Ticlopidin
      was started directly after stent implantation, abciximab was started before
      coronary intervention and given intravenously for 12 h, and a clopidogrel loading
      dose was given before intervention. The 10 patients treated with ticlopidin (500
      mg daily) showed no significant prolongation of PFA closure times and a slight
      increase of ADP-induced platelet aggregation shortly after intervention. In 11
      patients treated with abciximab/ticlopidin, the PFA closure times were
      significantly prolonged, and ADP-induced platelet aggregation was reduced by more
      than 80% during the 12-h abciximab infusion after intervention. The 10 patients
      pretreated with loading dose clopidogrel (450 mg followed by 75 mg daily) showed
      an intermediate but significant prolongation of PFA closure times and reduction
      of ADP-induced platelet aggregation at levels between the ticlopidin/aspirin- and
      the abciximab/ticlopidin/aspirin-treated groups. At 20 h after intervention, a
      similar degree of PFA closure time prolongation and inhibition of ADP-induced
      aggregation was observed in the abciximab/ticlopidin/aspirin- and the
      clopidogrel/aspirin-treated patient groups. Both measurement of PFA-100 closure
      times and inhibition of ADP-induced platelet aggregation showed a similar degree
      of platelet inhibition, but had rather broad SD ranges, which limit their
      precision for the follow-up of individual patients. In conclusion, abciximab on
      top of ticlopidin/aspirin showed a stronger antiplatelet effect for only less
      than 20 h, as compared to loading dose clopidogrel/aspirin in acute coronary
      syndrome patients undergoing stent implantation. Whether such a short-term
      superiority of abciximab, as compared to loading dose clopidogrel, translates
      into an overall clinical benefit of thombotic and bleeding complications remains
      to be established in a randomized clinical trial.

PMID- 14678815
TI  - Aspirin treatment does not attenuate platelet or leukocyte activation as
      monitored by whole blood flow cytometry.
AB  - Despite undoubtful clinical evidence of anti-platelet effects of aspirin,
      previous studies demonstrate little inhibition by aspirin treatment of single
      platelet activation as measured by flow cytometry. This discrepancy was further
      evaluated using flow cytometric measurements of circulating platelet-leukocyte
      aggregates (PLAs), which may be a more sensitive marker of platelet activation in
      vivo than measurements of activation markers on single platelets. Blood samples
      were obtained from 15 healthy subjects before and after aspirin treatment (75 and
      500 mg daily for 1 week). Platelet (P-selectin expression) and leukocyte (CD11b
      expression) activation and platelet-leukocyte aggregation were monitored by whole
      blood flow cytometry. Approximately 1% platelets in unstimulated samples were P
      selectin-positive, i.e., circulating activated platelets, and about 3% of
      leukocytes were circulating as PLAs; neither of these parameters were reduced by
      aspirin treatment. Circulating platelet micro-aggregates were not influenced by
      aspirin either. In vitro stimulation with ADP, thrombin, or PAF increased
      platelet P-selectin expression and thus PLA formation, but these responses were
      not affected by aspirin. Leukocyte CD11b expression, a marker of leukocyte
      secretion, was not significantly influenced by aspirin either in unstimulated
      samples or upon in vitro stimulation. Thus, the present data support the concept
      that thromboxane generation is of little importance for the activation of single
      platelets; the platelet inhibiting effect of aspirin is seen mainly in the
      presence of close cell-cell contact, which enhances the importance of
      thromboxane. Multiple mechanisms may contribute to the remarkable clinical anti
      thrombotic effect of aspirin.

PMID- 14678816
TI  - Platelet-monocyte complex formation: effect of blocking PSGL-1 alone, and in
      combination with alphaIIbbeta3 and alphaMbeta2, in coronary stenting.
AB  - BACKGROUND: Binding of platelet P-selectin to P-selectin glycoprotein ligand 1
      (PSGL-1) is an initial event in the interactions between platelets and monocytes.
      Platelet-monocyte complexes (PMCs) have been implicated in several vascular
      disease processes, including acute coronary syndromes (ACS) and complications
      after percutaneous coronary intervention (PCI). We investigated the effect of ex
      vivo blockade of PSGL-1, alone and in combination with blockade of the
      alphaMbeta(2) (Mac-1) and alpha(IIb)beta(3) (GP IIb/IIIa) integrins, on PMC
      formation. METHODS AND RESULTS: Dual-label flow cytometry was used to detect PMCs
      in the blood of 10 volunteers and 10 patients undergoing PCI who received
      intravenous GP IIb/IIIa antagonists. PSGL-1 blockade, both prior to and after
      platelet stimulation, markedly reduced the formation of PMCs. Concomitant ex vivo
      blockade of the alphaMbeta(2) and alpha(IIb)beta(3) integrins did not result in
      further decreases of PMCs compared to PSGL-1 blockade alone. Antagonism of PSGL-1
      also led to near elimination of leukocyte-platelet interactions under flowing
      conditions. CONCLUSION: Blockade of PSGL-1 alone is sufficient to inhibit and
      reverse the formation of PMCs following platelet stimulation. Concurrent
      antagonism of PSGL-1 and the alpha(IIb)beta(3) and alphaMbeta(2) integrins was
      not more effective than inhibition of PSGL-1 alone. These results suggest that
      platelet-monocyte complex formation is mostly dependent on PSGL-1.

PMID- 14678817
TI  - Enhanced menadione cytotoxicity in platelets isolated from streptozotocin-induced
      diabetic rats.
AB  - To study whether chemically induced cytotoxicity occurs in diabetic platelets,
      platelets isolated from rats made hyperglycemic (diabetic) by a prior intravenous
      administration of streptozotocin were incubated with menadione and the
      cytotoxicity was assessed by the amount of lactate dehydrogenase (LDH) released
      from the menadione exposed platelets as a function of time. Platelets isolated
      from diabetic rats released greater amount of LDH in response to menadione than
      those from normal rats. Consistent with this finding, induction of menadione
      cytotoxicity was not dependent on glutathione depletion, but on greater
      generation of free radicals in diabetic platelets. Greater sensitivity of
      diabetic platelets to the menadione-induced cytotoxicity was accompanied by
      release of serotonin from dense granules, suggesting that this mechanism
      contributes to cardiovascular diseases in diabetic subjects.

PMID- 14678819
TI  - Neonatal thrombosis in India: a report of 14 cases.

PMID- 14678818
TI  - Effect of age of Armagnac extract and duration of treatment on antithrombotic
      effects in a rat thrombosis model.
AB  - In a previous study, we had shown that freeze-dried extracts of 12-year-old
      Armagnac could inhibit ADP-induced platelet aggregation in a dose- and duration
      dependent manner, and reduce thrombus weight in an experimental rat arteriovenous
      shunt thrombosis model after 2-week oral treatment. Polyphenol content could
      however vary with age and origin of the brandy, and the onset and offset of the
      effect were not defined. To this end, we studied the effects of extracts of 5-,
      10- and 15-year-old Armagnac from two different producers at 1, 5 and 25 mg/kg
      orally for 15 days, on the same rat arteriovenous shunt thrombosis model. We then
      studied the effects of 1, 3, 7 and 15 days of oral treatment with 5 mg/kg
      extracts of a 5-year-old Armagnac, and the effect 1, 3 and 7 days after a 1-week
      oral treatment of the same extract at the same dose. There was a dose-dependent
      decrease in thrombus weight, which was similar for both Armagnac origins for all
      ages. Extracts of 5- and 10-year-old Armagnac were similar, and more potent than
      extracts from 15-year-old Armagnac. There was a progressive decrease in thrombus
      weight over duration of treatment to 7 days, to about 50% of initial thrombus
      weight. The effect disappeared within 3 days after stopping a 7-day treatment. We
      confirm the dose-, age- and duration-dependent inhibition of arteriovenous shunt
      thrombosis in vivo by Armagnac extracts in rats.

PMID- 14678820
TI  - Continuation of oral anticoagulation despite superficial siderosis.

PMID- 14678821
TI  - Computer model of the interaction of human TFPI-2 Kunitz-type serine protease
      inhibitor with human plasmin.

PMID- 14678822
TI  - Nr0b1 and its network partners are expressed early in murine embryos prior to
      steroidogenic axis organogenesis.
AB  - Ahch is an orphan nuclear receptor encoded by Nr0b1 on the murine X chromosome
      and is the ortholog of human DAX1. Nr0b1/NR0B1 expression at appropriate dosages
      is required for normal steroidogenic axis development: mutation of the human
      ortholog, NR0B1, results in adrenal hypoplasia congenita and hypogonadotropic
      hypogonadism; and duplication or transgenic overexpression in humans or mice,
      respectively, results in XY phenotypic females, a phenotype known as dosage
      sensitive sex-reversal. Complete loss of Nr0b1 by targeted deletion has been
      hypothesized to be lethal in embryonic stem (ES) cells and preliminary evidence
      suggested that ES cells might express Nr0b1. These investigations examined Nr0b1
      expression and its network partners in both cultured ES cells and preimplantation
      embryos. We cultured ES cells in the absence or presence of differentiation
      agents and analyzed expression of Nr0b1 and associated network partners by
      northern blot hybridization and reverse transcriptase-polymerase chain reaction.
      Nrob1 was highly expressed by totipotent ES cells with reduced expression
      following induction toward individual germ layer fates. Nr5a1/Sf1, Wt1 and other
      genes that encode proteins known to interact with Nr0b1 were also expressed.
      Immunohistochemical analysis of preimplantation embryos for Ahch and key partners
      confirmed in vivo expression of network components. These findings are consistent
      with the existence of a potentially functional network of transcription factors,
      including Ahch, very early in embryonic development. These results validate ES
      cells as a developmentally dynamic model for mechanistic investigations into this
      regulatory network early in embryogenesis preceding organogenesis.

PMID- 14678823
TI  - Molecular cloning and expression pattern of an armadillo homologue from the
      mulberry silkworm Bombyx mori.
AB  - Armadillo/beta-catenin, encoded by the segment polarity gene armadillo functions
      as a downstream effector of canonical Wnt signals. The expression patterns of Bm
      wnt-1, -Ci and -engrailed, suggested the presence of Wnt-1 network in the middle
      silkglands of Bombyx mori. To test this, a homologue of armadillo from B. mori
      (Bm arm) was cloned by PCR using degenerate primers, designed based on the
      conserved regions of the protein, and characterized. The cloned region harboured
      one complete and two incomplete Armadillo (Arm) repeat motifs and was highly
      conserved across species. Genomic Southern analysis suggested Bm arm to be a
      multi-copy gene. The expression of Bm arm RNA was first detected at stage 6 of
      embryogenesis, which reached maximum levels at stage 21C and was maintained until
      larval hatching. The RNA was expressed uniformly in the embryos, whereas the Arm
      protein was localized in a segmentally reiterated striped pattern, in conformity
      with its predicted segment polarity nature. Bm arm was also expressed in the
      entire silkgland and the transition from third to fourth and fifth larval
      intermoults was accompanied by an increase in the transcript levels. However, the
      Arm protein was predominantly localized to the middle silkglands, especially the
      middle and posterior sub-compartments. The silkglands represented a novel
      expression domain for arm in Bombyx, and the results were consistent with the
      existence of a canonical Wnt network in the middle silkglands.

PMID- 14678824
TI  - The early embryonic expression of TFII-I during mouse preimplantation
      development.
AB  - We studied the developmentally regulated expression of mouse TFII-I, a founding
      member of a family of transcription factors characterized by the presence of
      multiple helix-loop-helix repeat domains. TFII-I and BEN, a second member of this
      family, are involved in histone modification and SUMOylation. The genes, GTF2I
      and GTF2IRD1, encoding these proteins in human are located at chromosomal band
      7q11.23, within the Williams syndrome critical region. Our immunohistochemical
      analysis revealed extensive expression of TFII-I at early stages of
      embryogenesis. Like BEN, TFII-I is detected in the cytoplasm and nuclei of
      postfertilization through first cleavage stage embryos. However, in E4.5
      blastocysts, at the time of implantation, TFII-I is localized in the nucleus and
      cytoplasm of the inner cell mass (ICM) and trophectoderm. BEN, at this stage, is
      expressed only in the cytoplasm of trophoblast cells, but not in the ICM [Gene
      Expr. Patterns, 2003; 3, 577-587]. Using RT-PCR, we detected Gtf2i and Gtf2ird1
      mRNA transcripts in unfertilized oocytes, which indicates the maternal expression
      of these genes. Thus, the early embryonic expression of TFII-I implicates this
      family of transcription factors in preimplantation development.

PMID- 14678825
TI  - Embryonic expression of Xenopus laevis SOX7.
AB  - SOX7, first described in Xenopus laevis by Shiozawa et al. [Biochim. Biophys.
      Acta 1309(1996)73], is a member, along with SOXs 17 and 18, of the F subgroup of
      SOX-type transcription factors. As part of a study of maternal SOX proteins that
      may modulate beta-catenin signaling, we isolated a XSOX7 cDNA from oocyte RNA and
      examined the pattern of XSOX7 expression during early development. While present
      maternally cell-type specific expression was first observed in the ciliated cells
      within the epidermis of early neurula stage embryos. As development proceeds, the
      pattern of XSOX7 expression becomes increasingly complex. XSOX7 is expressed in
      the aortic arch, the olfactory pit, the stomodeal depression, the procardiac
      tube, within cells of the developing embryonic vasculature, in the notochord, and
      within the hindbrain. XSOX7 expression continues within the hindbrain in 3-day
      old ( approximately stage 40) larvae. Given its widespread expression, XSOX7 is
      likely to be involved in a number of developmental processes.

PMID- 14678826
TI  - Comparison of maf gene expression patterns during chick embryo development.
AB  - Maf proteins are basic-leucine zipper transcription factors belonging to the AP1
      superfamily. Several developmental processes require Maf proteins yet, the
      redundancy or complementarity of their respective roles in common processes has
      been only partially investigated. We present for the first time a complete
      comparative analysis of maf gene expression patterns in vertebrates. Expression
      of c-maf, mafB/kreisler, mafA/L-maf, mafF, mafG and mafK was analyzed by whole
      mount in situ hybridization within chick embryos and their extraembryonic tissues
      ranging from embryonic day (E) 1 to 7. We carefully examined the extent of
      overlap between distinct maf genes and report that the developing lens, kidney,
      pancreas and apoptotic zones of limb buds show sustained co-expression of large
      maf genes. Small maf genes also exhibit overlap, for example in the dermomyotome.
      We also describe so far unidentified sites of maf gene expression. mafA is found
      in the developing neural tube and dorsal root ganglia. c-maf hybridization is
      detected in the neuroretina, the notochord and the endothelium of extraembryonic
      blood vessels.

PMID- 14678827
TI  - Bsx, an evolutionary conserved Brain Specific homeoboX gene expressed in the
      septum, epiphysis, mammillary bodies and arcuate nucleus.
AB  - Shaping and orchestrating the genetic program involved in embryonic modelling of
      brain structures is a major function played by homeobox containing genes.
      Recently, analysis of conditional mouse mutants has pointed out additional roles
      in supporting adult brain functional activities. During a search for novel
      homeobox genes in the public released genomic sequences derived by the Human and
      Mouse genome projects, we were able to identify the mouse homologue of the
      Drosophila brain specific homeobox gene. We named it Bsx and characterized its
      expression in embryonic and post-natal mouse brain. Interestingly, Bsx shows an
      expression pattern restricted to a few specific developing brain structures.
      Pineal gland, telencephalic septum, hypothalamic pre-mammillary body and arcuate
      nucleus are the only brain structures where we detected Bsx transcriptional
      activity, which is maintained also after birth. In particular, Bsx might be
      considered an important molecular marker for early embryonic stages of epiphysis
      development, being specifically expressed in this neural structure from E9.5
      onwards.

PMID- 14678828
TI  - Parapineal specific expression of gfi1 in the zebrafish epithalamus.
AB  - We describe the isolation of zebrafish growth factor independent 1 (gfi1) and
      present an analysis of its pattern of expression during early development. As
      with its murine homologue, gfi1 expression is detected in the ganglion cells of
      the neural retina and in developing hair cells of the ear. In keeping with a role
      in the development of sensory hair cells, gfi1 is also expressed in neuromasts of
      the anterior and posterior lateral line system. Finally, gfi1 is expressed in the
      developing epithalamus in the dorsal diencephalon where its transcription is
      restricted to the parapineal.

PMID- 14678829
TI  - Spatial and temporal expression patterns of GDNF family receptor alpha4 in the
      developing chicken retina.
AB  - GDNF family receptor alpha (GFRalpha) receptors are involved in the regulation of
      different aspects of embryonic development such as proliferation, migration,
      differentiation and survival. To determine the possible role of GFRalpha4 in
      retinal development, we analysed its expression in the developing chicken retina.
      We found that GFRalpha4 is temporally co-expressed with c-ret. Both, the temporal
      and spatial expression of GFRalpha4 is developmentally regulated during
      retinogenesis and is first detected in cells of the ganglion cell layer at E6. As
      development of the retina proceeds, the expression of GFRalpha4 extends to cells
      of the inner half of the inner nuclear layer and to cells of the outermost cell
      row of the inner nuclear layer. Later on, GFRalpha4 expression is also found in
      additional cells of the outer half of the inner nuclear layer and in a
      subpopulation of photoreceptors. A central-to-peripheral gradient of retinal
      differentiation is evident, as the onset of GFRalpha4 expression is first
      detectable in the central retina, while it is delayed by two days in its
      periphery.

PMID- 14678830
TI  - Temporal and spatial expression of gonadotropin releasing hormone (GnRH) in the
      brain of developing zebrafish (Danio rerio).
AB  - Gonadotropin releasing hormone (GnRH) is a neuroendocrine decapeptide found in
      all vertebrate animals. The best understood function of GnRH is its endocrine
      function as a releasing hormone acting on the pituitary. But GnRH also functions
      as a neuromodulator within the nervous system. In a given species, GnRH occurs in
      a variety of forms that fall into three general categories based on pattern of
      protein/gene expression in the brain and amino acid sequence. The salmon GnRH
      (sGnRH), is found in the terminal nerve, where it has a neuromodulatory function.
      The sGnRH form is also the hypothalamic form in many fishes, although some fishes
      have a species specific form in the hypothalamus. Finally, chicken-GnRH-II (cGnRH
      II), the most highly conserved form, is found in the midbrain where its function
      remains unclear. Here we have cloned the sGnRH and cGnRH-II cDNAs from zebrafish.
      By conducting stage specific in situ hybridization in developing zebrafish
      embryos, we provide a description of the spatial and temporal expression patterns
      of these genes. The location of sGnRH and cGnRH-II expressing cells is in
      agreement with previous reports of GnRH in the brains of adult fishes. Our
      results provide the first developmental description of GnRH gene expression where
      cGnRH-II and sGnRH are initially expressed at the onset of the first day after
      fertilization. Unlike what has been reported in many adult fishes, we did not
      find sGnRH expressed in the hypothalamic population during development.

PMID- 14678831
TI  - Pancreatic protein disulfide isomerase (XPDIp) is an early marker for the
      exocrine lineage of the developing pancreas in Xenopus laevis embryos.
AB  - The pancreas develops from dorsal and ventral epithelial extensions at the
      foregut/midgut boundary in Xenopus embryos. Endocrine and exocrine specification
      is thought to occur from a pool of uniform precursor cells. While the genetic
      network controlling endocrine specification and differentiation has been the
      object of extensive investigations, the corresponding mechanism leading to the
      exocrine pancreas is much less understood. Here, we report on the identification
      and characterisation of a novel molecular marker for the early exocrine pancreas
      in Xenopus embryos. Xenopus pancreatic protein disulfide isomerase is expressed
      in both dorsal and ventral pancreatic buds. By whole mount in situ hybridization
      it is detected as early as stage 39 in the exocrine lineage of the developing
      pancreas; RT-PCR reveals onset of expression as early as stage 35/36.

PMID- 14678832
TI  - A putative ariadne-like E3 ubiquitin ligase (PAUL) that interacts with the muscle
      specific kinase (MuSK).
AB  - Formation of the postsynaptic membrane at the skeletal neuromuscular junction
      (NMJ) requires activation of the muscle-specific receptor tyrosine kinase (MuSK).
      Few intracellular mediators or modulators of MuSK actions are known. E3 ubiquitin
      ligases may serve this role, because activities of several receptor tyrosine
      kinases, G-protein-coupled receptors and channels are modulated by
      ubiquitination. Here, we report identification of a putative Ariadne-like
      ubiquitin ligase (PAUL) that binds to the cytoplasmic domain of MuSK. PAUL is
      expressed in numerous tissues of developing and adult mice, and is present at
      NMJs in muscle fibers but is not confined to them.

PMID- 14678833
TI  - The basic helix-loop-helix transcription factor, Tal2, marks the lateral floor
      plate of the spinal cord in zebrafish.
AB  - Basic helix-loop-helix (bHLH) transcription factors play key roles in the
      development of the central nervous system. Here we report the isolation of a
      zebrafish gene that encodes a homologue of the mammalian bHLH transcription
      factor, Tal2. In zebrafish embryos, tal2, like its mammalian homologue, is
      strongly expressed in the diencephalon and the mesencephalon, with the latter
      expression located in post-mitotic cells of the tectum. However, in addition to
      this conserved brain expression, we also detect expression in the floor plate of
      the spinal cord. By the location of this expression relative to other genes
      expressed in the floor plate and by analysing expression in a selection of
      midline mutants, we reveal that tal2 is expressed within the lateral floor plate
      as opposed to the medial floor plate, and also in more dorsal cells which are
      distinct from motorneurons and depend on either sonic hedgehog signalling or a
      signal coming from the lateral floor plate. This is to our knowledge the first
      report of a gene expressed specifically in lateral cells of the floor plate in
      the spinal cord.

PMID- 14678834
TI  - Cloning and expression of a leech complexin.
AB  - Release of neurotransmitter from presynaptic nerve terminals is mediated by SNARE
      proteins, which are located on the vesicle and plasma membranes. These proteins
      form a SNARE complex thought to mediate membrane fusion. Complexin is a soluble
      protein essential for transmitter release, which has been postulated to bind to
      and stabilise the SNARE complex. We have cloned a complexin homologue, Hm-cpx1,
      from the leech, Hirudo medicinalis. This protein is expressed in only a subset of
      neurons in the leech CNS, including the Retzius and P neurons. It is 33%
      identical to rat complexin I, and 44% identical to squid complexin. Sequence
      conservation is particularly high in the predicted SNARE binding domain.

PMID- 14678835
TI  - Rig-1 a new member of Robo family genes exhibits distinct pattern of expression
      during mouse development.
AB  - The Robo genes encode a family of proteins that are the receptors for the midline
      repellent Slits and play a role in axon guidance. In addition to Robo1 and Robo2,
      Rig-1 has been recently identified in mouse as a novel member of the Robo family
      of proteins. As a first step in elucidating the role of Rig-1 during vertebrate
      development, we characterised the expression of Rig-1 by in situ hybridisation
      together with Robo1 and Robo2 in the spinal cord and other tissues of the mouse
      embryo. Our results show that Rig-1 has a dynamic pattern of expression in the
      developing CNS. In the spinal cord Rig-1 shows overlapping but distinct pattern
      of expression with Robo1 and Robo2.

PMID- 14678836
TI  - Isolation and expression pattern of three mouse homologues of chick Rgm.
AB  - Growth cones of developing neurons are guided to their targets by attractive and
      repulsive cues. We have isolated three mouse homologues of the chick 'repulsive
      guidance molecule', Rgm [Nature 419 (2002) 392], and characterized their
      expression patterns. RgmA and RgmB are predominantly expressed in the developing
      and adult central nervous system in distinct patterns with little overlap. The
      third member of the Rgm gene family, RgmC, shows exclusive expression in the
      muscle cell lineage. From sequence and expression data, we suggest RgmA to be the
      mouse orthologue of chick Rgm.

PMID- 14678837
TI  - Expression of the RSK2 gene during early human development.
AB  - The 90 kDa ribosomal S6 serine/threonine kinase 2 gene (RSK2, U08316) has been
      recently identified as a disease-causing gene in an X-linked disorder, the Coffin
      Lowry Syndrome (MIM 303600) characterized by severe mental retardation, facial
      dysmorphisms and progressive skeletal malformations. To investigate its possible
      role in cerebral cortex development, we performed RNA in situ hybridization at
      three stages of human development: day 32 (Carnegie 15), 9 weeks (Carnegie 23)
      and 13 weeks. RSK2 expression is detected in the embryonic anterior and posterior
      telencephalon (hippocampus anlagen), mesencephalon, rhombencephalon and
      cerebellum. RSK2 gene expression is also observed in dorsal root ganglia, cranial
      nerve ganglia, and sensory epithelium of the inner ear, liver, lung and jaw
      anlagen. This pattern of expression may be involved in cognitive impairment and
      facial dysmorphisms found in Coffin-Lowry Syndrome.

PMID- 14678838
TI  - Laser talks in florence.

PMID- 14678840
TI  - Lasers and other thermal stimulators for activation of skin nociceptors in
      humans.
AB  - Pain can be induced by thermal, chemical, and mechanical stimulation in animals
      and man. Of the thermal stimulation modalities, heat is the most commonly used,
      as a variety of reliable stimulation techniques are available. Heat is a natural
      stimulus modality to evoke pain, and it has been used to study animal nociception
      and human pain perception for (a) examining the mechanisms of tissue injury and
      sensitisation and (b) quantifying the therapeutic effects of pharmacological,
      physical, and psychological interventions. This paper summarises the current
      understanding of the physiology and psychophysical response to painful heat
      stimulation in humans. By understanding the underlying mechanisms, new methods of
      heat stimulation may be developed for basic and clinical applications.
      Traditionally, contact heat, indirect thermal heat by focused light bulb, and
      laser pulses have been the methods used to induce heat pain in humans for
      experimental and clinical studies. The following lasers have been used in pain
      research: argon (488-515 nm), copper vapour (510-577 nm), semiconductor (e.g. 970
      nm), neodymium-YAG (1064 nm), thulium-YAG (2000 nm), and CO(2) (10,600 nm).

PMID- 14678841
TI  - How do we selectively activate skin nociceptors with a high power infrared laser?
      Physiology and biophysics of laser stimulation.
AB  - This review presents and discusses the leading arguments justifying the use of
      high power laser stimulators to explore the nociceptive system. To grasp the
      particularity of such stimulators, fundamentals concerning the interaction of low
      energy radiation with the skin will be recalled and focused on the optimal match
      between the wavelength of the emitting source and the thermophysical properties
      of the skin. This knowledge shall allow us to discuss critical characteristics of
      laser stimulators. Study of the cutaneous spectrum of receptors showed that laser
      stimulators allow the selective activation of A(delta) and C-fiber nociceptors.
      We will present different methods, which increase the selectivity of the laser
      stimulation, restricting the activation to isolated C-fiber nociceptors. These
      methods open new perspectives in the study of the cerebral processing of signals
      ascending through A(delta) and/or C nociceptors and should contribute to a better
      understanding of their central interaction and integration in normal and
      pathological states.

PMID- 14678842
TI  - Brain generators of laser-evoked potentials: from dipoles to functional
      significance.
AB  - In this work we review data on cortical generators of laser-evoked potentials
      (LEPs) in humans, as inferred from dipolar modelling of scalp EEG/MEG results, as
      well as from intracranial data recorded with subdural grids or intracortical
      electrodes. The cortical regions most consistently tagged as sources of scalp
      LERs are the suprasylvian region (parietal operculum, SII) and the anterior
      cingulate cortex (ACC). Variability in opercular sources across studies appear
      mainly in the anterior-posterior direction, where sources tend to follow the axis
      of the Sylvian fissure. As compared with parasylvian activation described in
      functional pain imaging studies, LEP opercular sources tended to cluster at more
      superior sites and not to involve the insula. The existence of suprasylvian
      opercular LEPs has been confirmed by both epicortical (subdural) and
      intracortical recordings. In dipole-modelling studies, these sources appear to
      become active less than 150 ms post-stimulus, and remain in action for longer
      than opercular responses recorded intracortically, thus suggesting that modelled
      opercular dipoles reflect a "lumped" activation of several sources in the
      suprasylvian region, including both the operculum and the insula. Participation
      of SI sources to explain LEP scalp distribution remains controversial, but
      evidence is emerging that both SI and opercular sources may be concomitantly
      activated by laser pulses, with very similar time courses. Should these data be
      confirmed, it would suggest that a parallel processing in SI and SII has remained
      functional in humans for noxious inputs, whereas hierarchical processing from SI
      toward SII has emerged for other somatosensory sub-modalities. The ACC has been
      described as a source of LEPs by virtually all EEG studies so far, with
      activation times roughly corresponding to scalp P2. Activation is generally
      confined to area 24 in the caudal ACC, and has been confirmed by subdural and
      intracortical recordings. The inability of most MEG studies to disclose such ACC
      activity may be due to the radial orientation of ACC currents relative to scalp.
      ACC dipole sources have been consistently located between the VAC and VPC lines
      of Talairach's space, near to the cingulate subsections activated by motor tasks
      involving control of the hand. Together with the fact that scalp activities at
      this latency are very sensitive to arousal and attention, this supports the
      hypothesis that laser-evoked ACC activity may underlie orienting reactions
      tightly coupled with limb withdrawal (or control of withdrawal). With much less
      consistency than the above-mentioned areas, posterior parietal, medial temporal
      and anterior insular regions have been occasionally tagged as possible
      contributors to LEPs. Dipoles ascribed to medial temporal lobe may be in some
      cases re-interpreted as being located at or near the insular cortex. This would
      make sense as the insular region has been shown to respond to thermal pain
      stimuli in both functional imaging and intracranial EEG studies.

PMID- 14678843
TI  - Contribution of attentional and cognitive factors to laser evoked brain
      potentials.
AB  - Painful stimuli delivered by infrared laser stimulators elicit laser-evoked
      potentials (LEP) or magnetic fields in respective electroencephalogram (EEG) and
      magnetoencephalogram (MEG). Evidence is reviewed that LEP represent a series of
      event-related potentials (ERP) that depend on vigilance and arousal, selective
      spatial attention and contextual task variables. Paradigms adopted from other
      stimulus modalities in the assessment of attention and cognition in ERP and
      applied to LEP allow the view that middle-latency (N1) and long latency (N2-P2)
      components of LEP can be overlapped or supplemented by endogenous components such
      as the processing negativity and distinct members (P3a and P3b) of the "P300"
      activities, each of which is considered in detail in this review. This composite
      entity needs to be considered when LEP are experimentally or clinically used in
      the assessment of sensory and cognitive phenomena and abnormalities of pain
      sensation.

PMID- 14678844
TI  - Clinical usefulness of laser-evoked potentials.
AB  - In contrast to the function of the visual or auditory pathways which are
      electrophysiologically accessible by visual or auditory evoked potentials, the
      somatosensory pathway cannot be investigated as a whole by conventional
      somatosensory evoked potentials (SEP), because these only reflect function of
      large fibers, dorsal columns, medial lemniscus and their thalamo-cortical
      projections mediating sensations like touch and vibration. The other half of the
      somatosensory system, signaling temperature and pain perception, uses a different
      set of afferents and different central pathways, the function of which is
      accessible by laser-evoked potentials (LEPs). LEP can document lesions of the
      spinothalamic tract and (lateral) brainstem and of thalamo-cortical projections
      conveying thermo-nociceptive signals. In the peripheral nerve, LEP can help
      distinguish between large and small fiber neuropathies. The rapid heating of the
      skin by infrared laser pulses can easily be applied to non-glabrous skin in any
      dermatome. In recent years, many clinical studies have demonstrated that LEP can
      supply evidence for establishing clinical diagnoses when deficits of the
      nociceptive system are present. This review outlines principles and recording
      techniques for LEP in patients and compiles typical LEP findings in patients with
      lesions due to different diseases at various levels of the nociceptive pathways.
      Limitations for the use of LEP are pointed out, too, like the uncertainty of
      lesion location along these pathways and the fact that LEP can reliably show
      correlates of reduced nociceptive function but only rarely of enhanced
      transmission (like in hyperalgesia).

PMID- 14678845
TI  - Trigeminal responses to laser stimuli.
AB  - The majority of the studies on laser evoked potentials (LEPs) have been focused
      on hand and foot stimulations and only lately on the trigeminal system. Because
      of a high receptor density in the facial skin and the very short conduction
      distance, LEP recordings after trigeminal stimulation are easier and quicker than
      those after stimulation of the limb extremities. Laser pulses with a stimulus
      intensity close to perception threshold can evoke well-defined LEPs. Few trials
      are sufficient to yield stable and reproducible averages. Even ultralate LEPs
      related to the C-fibre input are comparatively easily obtained from the
      trigeminal territory. The brain generators of the main LEP waves are probably
      very close for the trigeminal and limb stimulations. Trigeminal LEPs have been
      found absent or delayed in patients with trigeminal neuralgia, trigeminal
      neuropathies, posterior fossa tumors, and brainstem infarctions or demyelinating
      plaques. Conversely, trigeminal LEPs appear to be enhanced in patients with
      migraine. High-intensity pulses directed to any trigeminal division also elicit
      reflex responses: a blink-like reflex in the orbicularis oculi and a single
      silent period in the contracting masseter muscle. The availability of a
      neurophysiological method of assessing function of the trigeminal nociceptive
      pathways reaching both the cerebral cortex and the brainstem reflex circuits, has
      provided new opportunities for investigating the pathophysiology of orofacial
      pain syndromes.

PMID- 14678846
TI  - The role of vascular endothelial growth factor in glucocorticoid-induced bone
      loss: evaluation in a minipig model.
AB  - Vascular endothelial growth factor (VEGF) has been recently shown to play an
      important role during endochondral bone formation in hypertrophic cartilage
      remodeling, ossification, and angiogenesis. To our knowledge there are no
      previous studies investigating the role of VEGF in osteoporosis. We hypothesized
      that VEGF expression in bone would be reduced under glucocorticoid (GC) treatment
      and tested this in a minipig model. As part of a larger study, 17 primiparous
      sows (Gottingen minipig) were allocated to two experimental groups when they were
      15 months old: a control group (n = 9) and a group receiving GC treatment for 15
      months (n = 8). All animals were fed a semisynthetic diet until they were
      sacrificed. The GC group received prednisolone orally at a daily dose of 1 mg/kg
      body wt for 8 weeks and thereafter 0.5 mg/kg body wt. VEGF levels in lumbar
      vertebrae were measured by enzyme-linked immunosorbent assay (ELISA) and verified
      by Western blot analysis. VEGF and its receptors (VEGFR) were localized by
      immunohistochemistry. Expression of VEGF-mRNA was analyzed by reverse
      transcription-polymerase chain reaction. VEGF protein was quantified in
      supernatants of cultivated osteoblasts by ELISA. Spinal bone mineral density was
      assessed in vivo by quantitative computed tomography. Expression of
      cyclooxygenase-2 (COX-2) protein was investigated by immunohistochemistry. High
      VEGF concentrations were measured in normal lumbar vertebrae whereas VEGF
      concentrations were 60% lower (P < 0.0001) in GC-treated minipigs. VEGF levels
      were associated (r = 0.7) with rates of spinal trabecular bone loss, which
      differed significantly (P < 0.0013) between controls (-0.47 +/- 2.2% SEM) and GC
      treated minipigs (-12.8 +/- 2.3% SEM). Osteoblasts were immunopositive for VEGF.
      VEGF receptors VEGFR-2 (KDR, flk-1) and VEGFR-1 (flt-1) could be immunostained on
      osteoclasts and osteoblasts. VEGF-mRNA and protein were detectable in the lumbar
      vertebrae of all animals. The expression of COX-2 protein was decreased in GC
      treated animals. VEGF is produced in osteoblasts and its concentration is
      decreased in GC-treated animals as well as in osteoblasts exposed to GC. Since
      reductions in VEGF concentrations correlate with parallel measurement of bone
      mineral density in GC-treated minipigs we hypothesize that VEGF may be an
      important modulating factor for bone remodeling, specifically in GC-induced
      osteoporosis. GC inhibit COX-2 and hence prostaglandin E2 (PGE2) production.
      Since PGE2 is able to increase VEGF synthesis, this may be the link between GC
      and VEGF decrease.

PMID- 14678847
TI  - Bone mineral density reference standards in adult baboons (Papio hamadryas) by
      sex and age.
AB  - Osteoporosis is a progressive condition involving structural deterioration of
      bone tissue, leading to skeletal fragility and an increased susceptibility to
      fractures due to low bone mass and high rates of bone turnover. Areal bone
      mineral density (aBMD) serves as the most reliable predictor of susceptibility to
      osteoporotic fracture. The development of animal models, including Old World
      Monkeys, has been essential to studies of bone mineral density. These animals,
      including the baboon, exhibit many biological similarities with our own species
      relevant to the variation in age-related changes and pathology in bone that may
      make them an excellent model for studies of skeletal structure and maintenance in
      humans. The baboon has been shown to exhibit extensive biological similarities to
      humans regarding skeletal biology, but little is known about the range of normal
      variation in skeletal traits, such as bone mineral density, in this species. Our
      data, collected on baboons (Papio hamadryas) that are part of a large breeding
      colony at the Southwest Foundation for Biomedical Research and the Southwest
      National Primate Research Center (San Antonio, TX), involve 466 females and 210
      males, ranging in age from 5.5 to 30 years. Student's t tests, bivariate
      correlations, and likelihood ratio tests show sex and age effects at all spinal
      sites. Age effects are minimal or absent in the forearm sites. This study is the
      first to characterize normal variation in aBMD in baboons, to assess the effect
      of age and sex on this variation, and to compare this variation to those data
      currently available from experimental control animals. As such, it provides much
      needed reference standards that will allow researchers to evaluate the status of
      their animals in cross-sectional studies and more fully assess the meaning of
      aBMD changes in longitudinal studies.

PMID- 14678848
TI  - Expression of angiogenic factors during distraction osteogenesis.
AB  - Distraction osteogenesis is a unique and effective way to treat limb length
      inequality resulting from congenital and posttraumatic skeletal defects. However,
      despite its widespread clinical use, the cellular and molecular mechanisms by
      which this surgical treatment promotes new bone formation are not well
      understood. Previous studies in distraction osteogenesis have noted increased
      blood flow and vessel formation within the zone of distraction. These
      observations suggest that distraction osteogenesis may be driven in part by an
      angiogenic process. Using immunohistological analysis, the expression of two
      different angiogenic factors (VEGF and bFGF) was shown to localize at the leading
      edge of the distraction gap, where nascent osteogenesis was occurring. These
      cells were spatially adjacent to new vessels that were identified by staining for
      factor VIII. Microarray analysis detected maximal mRNA expression for a wide
      variety of angiogenic factors including angiopoietin 1 and 2, both Tie receptors,
      VEGF-A and -D, VEGFR2, and neuropilin 1. Expression of these factors was found to
      be maximal during the phase of active distraction. Expression of mRNA for
      extracellular matrix proteins and BMPs was also maximal during this period. A
      comparison between the patterns of gene expression in fracture healing and
      distraction osteogenesis revealed similarities; however, the expression of a
      number of genes showed selective expression in these two types of bone healing.
      These data suggest that bone formation during distraction osteogenesis is
      accompanied by the robust induction of factors associated with angiogenesis and
      support further investigations to elucidate the mechanisms by which angiogenic
      events promote bone repair and regeneration.

PMID- 14678849
TI  - Hedgehog stimulates only osteoblastic differentiation of undifferentiated KS483
      cells.
AB  - The involvement of hedgehog signaling in the initiation of osteoblastic
      differentiation in the bone collar during endochondral bone formation has been
      well established. The stages at which hedgehog acts during osteoblast
      differentiation as well as its molecular mechanism of action are less well
      understood. To address these questions, we have made use of the preosteoblastic
      cell line KS483. First, a systematic survey of mRNA expression of osteoblastic
      differentiation showed expression of Ihh and signaling intermediates at all
      stages. Interestingly, expression of Ihh, Gli1 and Ptc1 peaked during the
      maturation phase. Addition of recombinant human sonic hedgehog (rShh) potently
      increased osteoblastic differentiation of KS483 cells dose-dependently as assayed
      by a modest increase in alkaline phosphatase (ALP) activity, a strong increase in
      matrix mineralization, and increased mRNA expression of established osteoblast
      marker genes. These effects were blocked by the hedgehog antagonist cyclopamine,
      which by itself was ineffective. Addition of rShh during early stages was
      sufficient, while addition to mature osteoblasts had no effect. Furthermore,
      hedgehog signaling could be completely blocked by the BMP antagonists, soluble
      truncated BMPR-IA and noggin. In contrast, the BMP-induced differentiation of
      KS483 cells could only be partly inhibited by high doses of cyclopamine. These
      data demonstrate that Hh-induced osteoblastic differentiation requires functional
      BMP signaling. In KS483 cells, Hh and BMP synergistically induced alkaline
      phosphatase activity only when suboptimal concentrations of BMP were used. This
      synergy did not occur at the level of immediate early BMP response, but at the
      level of Hh response as determined by transient transfection studies using either
      a BMP reporter or a Gli reporter construct. In addition, rShh inhibited
      adipogenesis of KS483 cells cultured under adipogenic culture conditions,
      suggesting that Hh is involved in directing differentiation of KS483 cells toward
      osteoblasts at the expense of adipogenesis. Using in situ hybridization, we
      demonstrated, for the first time, Ihh mRNA expression in vivo in osteoblasts and
      lining cells in the humerus of developing human skeleton. Our in vitro and in
      vivo data indicate a stimulatory role for osteoblast-expressed Ihh in bone
      formation in a positive feedback loop. It may recruit progenitor cells in the
      osteoblastic lineage at the expense of adipocytes and it may stimulate maturation
      of early osteoblasts.

PMID- 14678850
TI  - Connective tissue growth factor mRNA expression pattern in cartilages is
      associated with their type I collagen expression.
AB  - Connective tissue growth factor (CTGF) has been identified as a secretory protein
      encoded by an immediate early gene and is a member of the CCN family. In vitro
      CTGF directly regulates the proliferation and differentiation of chondrocytes;
      however, a previous study showed that it was localized only in the hypertrophic
      chondrocytes in the costal cartilages of E 18 mouse embryos. We described the
      expression of CTGF mRNA and protein in chondrocytes of different types of
      cartilages, including femoral growth plate cartilage, costal cartilage, femoral
      articular cartilage, mandibular condylar cartilage, and cartilage formed during
      the healing of mandibular ramus fractures revealed by in situ hybridization and
      immunohistochemistry. To characterize the CTGF-expressing cells, we also analyzed
      the distribution of the type I, type II, and type X collagen mRNA expression.
      Among these different types of cartilages we found distinct patterns of CTGF mRNA
      and protein expression. Growth plate cartilage and the costal cartilage showed
      localization of CTGF mRNA and protein in the hypertrophic chondrocytes that
      expressed type X collagen mRNA with less expression in proliferating chondrocytes
      that expressed type II collagen mRNA, whereas it was also expressed in the
      proliferating chondrocytes that expressed type I collagen mRNA in the condylar
      cartilage, the articular cartilage, and the cartilage appearing during fracture
      healing. In contrast, the growth plate cartilages or the costal cartilages were
      negative for type I collagen and showed sparse expression of CTGF mRNA in the
      proliferating chondrocytes. We found for the first time that CTGF mRNA could be
      differentially expressed in five different types of cartilage associated with
      those expressing type I collagen. Moreover, the spatial distribution of CTGF mRNA
      in the cartilages with type I collagen mRNA suggested its roles in the early
      differentiation, as well as in the proliferation and the terminal
      differentiation, of those cartilages.

PMID- 14678851
TI  - Aging is associated with decreased maximal life span and accelerated senescence
      of bone marrow stromal cells.
AB  - Age-related decrease in bone formation is well described. However, the cellular
      causes are not known. Thus, we have established cultures of bone marrow stromal
      cells (MSC) from young (aged 18-29 years, n = 6) and old (aged 68-81 years, n =
      5) donors. MSC were serially passaged until reaching maximal life span. Cell
      growth, markers of cellular senescence, and osteogenic and adipogenic potential
      were determined in early-passage and late-passage cells established from young
      and old donors. MSC from old donors exhibited a decreased maximal life span
      compared with cells from young donors (24 +/- 11 population doublings [PD] vs 41
      +/- 10 PD, P < 0.05) and mean PD rate was lower in old donor cells (0.05 +/- 0.02
      PD/day) compared with young donor cells (0.09 +/- 0.02 PD/day) (P < 0.05). No
      differences were detected in number of senescence-associated beta-galactosidase
      positive (SA beta-gal+) cells and mean telomere length in early-passage cells
      obtained from young and old donors. However, MSC from old donors exhibited
      accelerated senescence evidenced by increased number of SA beta-gal+ cells per PD
      as compared with young (4% per PD vs 0.4% per PD, respectively). MSC from young
      and old donors were able to form similar amounts of mineralized matrix in vitro
      and of normal lamellar bone in vivo. In adipogenic medium similar numbers of
      adipocytes formed in cultures of young and old donors. In conclusion, aging is
      associated with decreased proliferative capacity of osteoprogenitor cells,
      suggesting that decreased osteoblastic cell number, and not function, leads to
      age-related decrease in bone formation.

PMID- 14678852
TI  - A substance P receptor (NK1) antagonist enhances the widespread osteoporotic
      effects of sciatic nerve section.
AB  - The long-term effects of sciatic nerve section on bone mineral density (BMD) were
      studied using dual-energy X-ray absorptiometry (DEXA) in skeletally mature rats.
      Unilateral sciatic neurectomy caused the rapid loss of cancellous bone in the
      proximal and distal femur and tibia in the ipsilateral hindlimb and, to a lesser
      extent, in the contralateral intact hindlimb. The reduction in BMD rapidly
      progressed for 4 weeks after sciatic section and then gradually stabilized with
      no evidence of recovery at 12 weeks. The development of osteoporosis in the
      contralateral intact hindlimb was a novel finding. There was no evidence of
      disuse in the normal contralateral hindlimb after unilateral sciatic section;
      grid-crossing activity over a 24-h interval was unchanged and there was no
      reduction in weight bearing on the contralateral normal hindpaw during the stance
      phase of ambulation. Unilateral peripheral nerve lesions have well-documented
      effects on substance P content and function in the corresponding contralateral
      intact nerve. We hypothesized that after sciatic section a reduction in substance
      P signaling might contribute to bone loss in the contralateral hindlimb. Daily
      administration of the substance P receptor (NK1) antagonist LY303870 for 2 weeks
      caused significant loss of cancellous bone in the denervated and the
      contralateral hindlimb, evidence that substance P signaling sustained bone
      density after nerve section. After sciatic neurectomy there was a 33% reduction
      in sciatic nerve stimulation-evoked extravasation in the contralateral intact
      hindlimb, indicating transmedian inhibition of substance P signaling after nerve
      injury. Furthermore, there was a 50% reduction in the substance P content in both
      tibias after unilateral sciatic section. Collectively, these data support the
      hypothesis that a widespread reduction in substance P content in bone contributes
      to the osteoporotic effects of sciatic neurectomy and that residual substance P
      signaling maintains bone integrity after nerve section in both the denervated and
      contralateral intact hindlimb.

PMID- 14678853
TI  - Mechanical consequences of different scenarios for simulated bone atrophy and
      recovery in the distal radius.
AB  - Metabolic bone diseases such as osteoporosis usually cause a decrease in bone
      mass and a deterioration of bone microarchitecture leading to a decline in bone
      strength. Methods to predict bone strength in patients are currently based on
      bone mass only. It has been suggested that an improved prediction of bone
      strength might be possible if structural changes are taken into account as well.
      In this study we evaluated which structural parameters (other than bone mass) are
      the best predictors for changes in bone mechanical properties of the human radius
      after different bone atrophy scenarios and whether the original strength of the
      affected bone can be recovered if bone loss is restored by thickening of the
      remaining structures. To answer these questions, a human radius was measured with
      a microcomputer tomography scanner to extract the full three-dimensional
      architecture of the distal radius at an isotropic resolution of 80 microm. Eight
      models with modified bone architecture were created and the mechanical variations
      due to these modifications were studied using microfinite element (micro-FE)
      simulations. In four models mass was lowered by 20%, either by reducing cortical
      thickness, trabecular thickness, or number of trabeculae or by overall thinning
      of structures. In the other four models bone mass was restored to the original
      value using a trabecular bone thickening procedure. The micro-FE analyses
      revealed that most load was carried by the cortical bone. For this reason, bone
      strength was affected most in the reduced cortical thickness model. For the same
      reason, the trabecular bone atrophy scenarios, all of which affected bone
      strength in a very similar way, resulted in less dramatic bone strength
      reduction. The restoration of bone mass did not recover the original bone
      strength. These findings demonstrate that the importance of different parameters
      for the prediction of bone strength also depends on the mechanical loading. This
      could explain why results of earlier studies on the importance of structural
      parameters can be inconsistent and site-dependent.

PMID- 14678854
TI  - Enabling bone formation in the aged skeleton via rest-inserted mechanical
      loading.
AB  - The mild and moderate physical activity most successfully implemented in the
      elderly has proven ineffective in augmenting bone mass. We have recently reported
      that inserting 10 s of unloaded rest between load cycles transformed low
      magnitude loading into a potent osteogenic regimen for both adolescent and adult
      animals. Here, we extended our observations and hypothesized that inserting rest
      between load cycles will initiate and enhance bone formation in the aged
      skeleton. Aged female C57BL/6 mice (21.5 months) were subject to 2-week
      mechanical loading protocols utilizing the noninvasive murine tibia loading
      device. We tested our hypothesis by examining whether (a) inserting 10 s of rest
      between low-magnitude load cycles can initiate bone formation in aged mice and
      (b) whether bone formation response in aged animals can be further enhanced by
      doubling strain magnitudes, inserting rest between these load cycles, and
      increasing the number of high-magnitude rest-inserted load cycles. We found that
      50 cycles/day of low-magnitude cyclic loading (1200 microepsilon peak strain) did
      not influence bone formation rates in aged animals. In contrast, inserting 10 s
      of rest between each of these low-magnitude load cycles was sufficient to
      initiate and significantly increase periosteal bone formation (fivefold versus
      intact controls and twofold versus low-magnitude loading). However, otherwise
      potent strategies of doubling induced strain magnitude (to 2400 microepsilon) and
      inserting rest (10 s, 20 s) and, lastly, utilizing fivefold the number of high
      magnitude rest-inserted load cycles (2400 microepsilon, 250 cycles/day) were not
      effective in enhancing bone formation beyond that initiated via low-magnitude
      rest-inserted loading. We conclude that while rest-inserted loading was
      significantly more osteogenic in aged animals than the corresponding low
      magnitude cyclic loading regimen, age-related osteoblastic deficits most likely
      diminished the ability to optimize this stimulus.

PMID- 14678855
TI  - Relation of homocysteine, folate, and vitamin B12 to bone mineral density of
      postmenopausal women.
AB  - Genetic hyperhomocysteinemia is associated with skeletal abnormalities and
      osteoporosis. We tested whether levels of homocysteine and critical co-enzymes of
      homocysteine metabolism, such as vitamin B12 and folate, are related to lumbar
      spine bone mineral density (BMD) measured by DEXA in 161 postmenopausal women.
      Folate but not homocysteine or vitamin B12, was lower in osteoporotic than normal
      women (7.2 +/- 0.9 ng/L vs 11.4 +/- 0.7 ng/L, P < 0.003). Folate, but not
      homocysteine or vitamin B12, was independently related to BMD (r = 0.254, P <
      0.011). BMD progressively increased from the lowest to the highest folate
      quartile (1.025 +/- 0.03 g/cm2 vs 1.15 +/- 0.03 g/cm2, P < 0.01) even when
      covaried for weight, which was the only other variable related to BMD. The
      present data suggest a major association between folate and bone mineralization.

PMID- 14678856
TI  - Tissue mineralization is increased following 1-year treatment with high doses of
      bisphosphonates in dogs.
AB  - Suppression of bone turnover using anti-resorptive agents such as bisphosphonates
      prevents bone loss but also may increase tissue mineralization. This may make the
      bone more prone to initiate microcracks. The objective of this study was to
      determine whether suppression of remodeling caused by treatment of dogs for 1
      year with five times the clinical dose of either alendronate or risedronate is
      associated with increased tissue mineralization and whether it changes the nature
      of the mineral crystal. Thirty-five dogs were divided into three weight-matched
      groups and treated daily for 1 year with a subcutaneous injection of saline (CON,
      n = 12), oral risedronate (RIS, 0.5 mg/kg/day, n = 11), or oral alendronate (ALN,
      1.0 mg/kg/day, n = 12). Density fractionation, peripheral quantitative
      computerized tomography (pQCT), and quantitative backscattered electron
      microscopy (qBSE) were used to evaluate changes in mineral content of bone tissue
      from the vertebrae or ribs. Infrared microspectroscopy (IR) and X-ray diffraction
      were used to assess the quality of the mineral and some aspects of collagen
      structure in the thoracic vertebrae and iliac crest. Following 12 months of
      treatment, there was a significant shift toward higher density bone in both ALN
      (P = 0.04) and RIS (P = 0.002) by density fractionation methods. IR, pQCT, and
      qBSE did not detect any significant differences in mineralization, probably
      because of their lower sensitivity and/or because of the smaller region of
      interest they sample. No significant differences were found in the maturity of
      the mineral crystals or in their length or size. We conclude that treatment for 1
      year with high doses of bisphosphonates which suppress bone remodeling up to 90%
      increases tissue mineralization, but does not change the nature of the mineral
      crystal.

PMID- 14678857
TI  - Screening for asymptomatic celiac disease among patients referred for bone
      densitometry measurement.
AB  - Celiac disease (CD) is a relatively common gastrointestinal disorder that can be
      asymptomatic. An increased prevalence of subclinical CD has been reported in many
      populations. Even among asymptomatic patients a reduction in bone mineral density
      (BMD) has been observed. The aim of this study was to evaluate the prevalence of
      silent CD in a cohort of consecutive individuals referred for bone densitometry
      measurement. Serum samples were taken from 454 women attending for bone
      densitometry (mean age: 56 +/- 11 years). Of the individuals evaluated, 89 had
      normal BMD and 365 had low BMD (T score < -1.0). Subjects were screened for the
      presence of serum IgA anti-endomysial antibodies (EMA) and IgA tissue
      transglutaminase (tTG) antibodies by indirect immunofluorescence and enzyme
      linked immunosorbent assay (ELISA), respectively. BMD was measured by dual X-ray
      absorptiometry (DEXA) at the lumbar spine and femoral neck. Eight EMA tTG
      positive individuals were identified in this population (1.8% or 1:57).
      Serologically positive women had a lower mean Z score at both the lumbar spine
      and femoral neck than EMA tTG-negative women. But this did not approach
      significance. There was no significant difference in the incidence of CD between
      the normal- and low-BMD groups in this dataset (P = 0.365). In conclusion, our
      study indicates that the prevalence of CD in our dataset is high. However, the
      frequency of asymptomatic CD among low-BMD individuals is similar to that among
      normal-BMD individuals in our population. These observations do not support the
      hypothesis that serological testing for CD may be a good accompaniment to DEXA
      scanning.

PMID- 14678858
TI  - Evaluating the cardiovascular effects of the thiazolidinediones and their place
      in the management of type 2 diabetes mellitus. Proceedings of a symposium.
      November 6-8, 2002, New York, New York, USA.

PMID- 14678859
TI  - Hyperglycemia as a cardiovascular risk factor.
AB  - Patients with type 2 diabetes mellitus have a 2- to 4-fold increased risk of
      coronary heart disease (CHD) and a 4-fold increase in mortality from CHD.
      Intensive glycemic control has a more modest effect on reducing macrovascular
      complications than microvascular complications. Most likely, this is because the
      development of cardiovascular disease is multifactorial, and hyperglycemia is 1
      of many risk factors. Epidemiologic data suggest that a glycosylated hemoglobin
      (A(1c)) level of < or =7% is reasonable to avoid or minimize the complications
      associated with type 2 diabetes. Studies have shown that there is an increased
      risk of cardiovascular mortality before the onset of type 2 diabetes. The
      presence of CHD before the onset of clinical diabetes provides strong evidence
      for a strategy of diabetes prevention in at-risk patients. Data indicate that the
      atherogenic pattern of changes in the prediabetic state is seen primarily in
      insulin-resistant patients rather than in those with abnormally low insulin
      secretion. Therefore, strategies to prevent or treat type 2 diabetes should focus
      on improving insulin sensitivity. Clinical trials have demonstrated that
      lifestyle changes (e.g., diet and exercise) as well as use of metformin,
      acarbose, or troglitazone reduce the incidence of type 2 diabetes. Prevention of
      type 2 diabetes may be an important strategy to delay or prevent cardiovascular
      disease in many individuals.

PMID- 14678860
TI  - The roles of insulin resistance, hyperinsulinemia, and thiazolidinediones in
      cardiovascular disease.
AB  - Although it is difficult to distinguish between the relative effects of insulin
      resistance and hyperinsulinemia, insulin resistance is clearly associated with
      significantly increased cardiovascular and cerebrovascular risk. This effect is
      consistent across the spectrum of worsening glycemic control, from the onset of
      impaired glucose tolerance to the development of clinical diabetes. It is more
      difficult to discriminate between the roles of elevated circulating insulin and
      proinsulin levels; the association between insulin levels and cardiovascular risk
      is weak. The thiazolidinediones (TZDs) significantly improve insulin sensitivity
      and exert numerous effects on the vascular bed, including improved endothelial
      function, decreased vascular inflammation, decreased plasma free fatty acid
      levels, improved dyslipidemic profiles, and inhibition of vascular smooth muscle
      proliferation. These findings provide increasing evidence to suggest that the
      TZDs may have a beneficial effect on atherosclerosis and may reduce the incidence
      and severity of adverse cardiovascular outcomes. These effects remain to be
      substantiated by the results of large outcomes studies to evaluate the impact of
      glycemic control and reversal of insulin resistance on cardiovascular events.

PMID- 14678861
TI  - Beta-cell rejuvenation with thiazolidinediones.
AB  - Type 2 diabetes mellitus manifests in an insulin-resistant individual when
      pancreatic beta-cells are unable to produce sufficient insulin to overcome
      insulin resistance in the muscles and liver. There is a growing body of evidence
      that the thiazolidinedione (TZD) class of antidiabetic agents rejuvenates beta
      cells and improves their function. When combination therapy with a sulfonylurea
      drug and metformin fails, treatment with a TZD increases C-peptide
      concentrations, reflecting improvement in beta-cell function. Further evidence of
      TZD-induced preservation of beta-cell function is documented by the findings of
      several recent trials in diabetes prevention. This apparent ability of TZDs to
      rejuvenate beta-cells, in addition to improving insulin resistance and glycemic
      control, is a compelling reason to use these agents as initial therapy for type 2
      diabetes.

PMID- 14678862
TI  - Dyslipidemia in the metabolic syndrome and type 2 diabetes mellitus.
AB  - Patients with type 2 diabetes mellitus or the metabolic syndrome have a unique
      dyslipidemia characterized by hypertriglyceridemia; elevated blood levels of
      apolipoprotein B; small, dense low-density lipoprotein (LDL) cholesterol; and low
      levels of high-density lipoprotein (HDL) cholesterol, in particular HDL(2)-C.
      Treatment of the dyslipidemia associated with these disorders should focus on
      correcting the abnormal lipoprotein levels as well as LDL and HDL heterogeneity.
      Statins and fibrates are useful for treating elevated LDL in patients with and
      without diabetes or the metabolic syndrome. In addition, thiazolidinediones or
      niacin in combination with a statin show promise for correcting defects in LDL
      and HDL heterogeneity. The ultimate goal of treatment in this patient population
      is to prevent the development and progression of coronary artery disease.

PMID- 14678863
TI  - Free fatty acids and type 2 diabetes mellitus.
AB  - Acute elevation of plasma free fatty acids (FFAs) is necessary for insulin
      secretion. Sustained elevation, however, leads to apoptosis of pancreatic beta
      cells and is a major risk factor for cardiovascular disease and sudden death in
      patients with insulin resistance or a family history of diabetes mellitus, as
      well as in individuals with normal glucose tolerance. Data suggest that reduction
      of FFA plasma levels may reduce the incidence of cardiovascular disease in these
      at-risk patients. Thiazolidinediones have been shown not only to improve insulin
      sensitivity but also to reduce FFA plasma levels. Consequently, endothelial
      function is maintained, vascular smooth muscle cell proliferation and migration
      are minimized, elevated blood pressure and microalbuminuria are reduced, and high
      density lipoprotein and low-density lipoprotein cholesterol particle sizes are
      improved.

PMID- 14678864
TI  - Obesity as a cardiovascular risk factor.
AB  - The prevalence of overweight and obesity continues to increase rapidly in the
      United States, with more than half of all adults currently overweight or obese.
      In general, people become obese because of a combination of inherited genes and a
      lifestyle consisting of low levels of physical activity and consumption of excess
      calories. Obesity, especially the central or visceral type, is a predisposing
      factor for the development of type 2 diabetes mellitus, hypertension, and
      cardiovascular disease (CVD). Obesity and type 2 diabetes are associated with
      insulin resistance. The relation among obesity, insulin resistance, and CVD
      appears to develop at a relatively young age. Central obesity is linked with
      hyperinsulinemia, insulin resistance, dyslipidemia, and proinflammatory and
      prothrombotic clinical states. Adipose tissue synthesizes and secretes
      biologically active molecules that may affect CVD risk factors. These chemical
      messengers include adiponectin, resistin, leptin, plasminogen activator inhibitor
      1, tumor necrosis factor-alpha, and interleukin-6. In overweight and obese
      individuals, weight loss may improve insulin sensitivity, leading to reduction in
      risk factors for CVD and, consequently, the potential for cardiovascular events.
      Agents that improve insulin sensitivity, such as the thiazolidinediones, have
      been shown to reduce visceral obesity. Decreases in visceral adipose tissue
      contribute to improvements in insulin sensitivity and blood pressure, and weight
      loss reduces serum levels of triglycerides and low-density lipoprotein
      cholesterol while increasing serum levels of high-density lipoprotein
      cholesterol. Reduction of risk factors suggests that the development of
      cardiovascular disease will be reduced by the improvement of insulin sensitivity
      and weight loss.

PMID- 14678865
TI  - Effect of thiazolidinediones on body weight in patients with diabetes mellitus.
AB  - Treatment of diabetes mellitus with medications, including insulin,
      sulfonylureas, and thiazolidinediones (TZDs), often leads to weight gain through
      a variety of mechanisms. Weight gain can have adverse consequences for patients
      with type 2 diabetes, many of whom are overweight or obese, because obesity is
      linked to insulin resistance and other medical consequences such as
      cardiovascular disease. TZDs improve glycemic control and insulin sensitivity in
      patients with type 2 diabetes, despite their potential to cause weight gain.
      Studies have attempted to elucidate the mechanisms behind the apparent paradox of
      TZDs improving insulin sensitivity while causing weight gain. Data indicate that
      with TZD treatment, there is a favorable shift in fat distribution from visceral
      to subcutaneous adipose depots that is associated with improvements in hepatic
      and peripheral tissue sensitivity to insulin. Although weight gain may occur with
      TZD therapy, it is not inevitable. A weight-management program combining a low
      calorie, low-sodium diet with education and behavior modification has been shown
      to be effective in patients with type 2 diabetes being treated with TZDs. Further
      research is needed to define the optimal dietary modifications that can be used
      universally in TZD-treated patients to minimize weight gain while effectively
      treating insulin resistance and hyperglycemia.

PMID- 14678866
TI  - Hypertension and nephropathy.
AB  - Nearly 90% of patients with hypertension and diabetes mellitus do not reach the
      recommended systolic blood pressure goal of <130 mm Hg. Consequently, the risk of
      cardiovascular and renal complications remains significant in this patient
      population. Study results suggest that initiating therapy with inhibitors of the
      renin-angiotensin system and adding diuretics may be useful in reducing arterial
      pressure to levels <130 mm Hg and may attenuate the progression of nephropathy.
      Recently, numerous studies have also found that the thiazolidinediones (TZDs) may
      improve insulin resistance and exert beneficial vascular effects in patients with
      type 2 diabetes. The TZDs have a range of vascular benefits, including mediating
      vasorelaxation, inhibiting angiogenesis, and improving inflammation. These
      findings have been associated with reduction in blood pressure and prevention of
      microalbuminuria. In patients with type 2 diabetes, early use of TZDs may be
      beneficial in both achieving glucose control and reducing the development or
      worsening of microalbuminuria or hypertension.

PMID- 14678867
TI  - The vascular biology of atherosclerosis.
AB  - Despite many advances in cardiology, atherosclerosis remains a major medical
      problem. This is especially the case for individuals with insulin resistance and
      type 2 diabetes mellitus. Atherosclerotic lesions can develop as early as the
      second decade of life and progress into clinical disease over time.
      Atherosclerosis is a complex disorder, involving many cell types and circulating
      mediators and resulting in an inflammatory state. The control of transcription of
      inflammatory mediators via ligands for peroxisome proliferator-activated receptor
      gamma, such as thiazolidinediones (TZDs), has been raised as a possible mechanism
      for improving atherosclerosis. Results of studies performed in vitro and in
      animal models suggest that TZDs may increase cholesterol efflux from macrophages,
      decrease cytokine expression, and limit chemokine levels. Such effects may
      underlie the decreases in atherosclerosis seen in mouse models of atherosclerosis
      after TZD treatment. The direct actions of the TZDs on atherosclerosis may couple
      with their effects on metabolic parameters through increased insulin sensitivity.
      Ongoing clinical trials evaluating cardiovascular end points with TZD therapy
      should provide insight into these possibilities.

PMID- 14678868
TI  - Effect of plasminogen activator inhibitor-1 in diabetes mellitus and
      cardiovascular disease.
AB  - Concentrations of plasminogen activator inhibitor-1 (PAI-1) are elevated
      beginning at the stage of impaired glucose tolerance and continuing through the
      development of diabetes mellitus and the metabolic syndrome. Evolving evidence of
      the central role of PAI-1 in mediating fibrosis and thrombosis increasingly
      supports the theory that it is a significant risk factor for macrovascular
      complications and cardiovascular disease, particularly in patients with diabetes.
      Several clinical studies have demonstrated a strong correlation between
      circulating PAI-1 levels and cardiovascular events and mortality. With the
      potentially severe effects of elevated PAI-1 levels becoming evident, there is
      increased interest in developing therapies targeted at reducing PAI-1 expression
      or circulating concentrations. Thus far, weight loss, inhibitors of the renin
      angiotensin system, and insulin sensitization through use of thiazolidinediones
      (TZDs) appear to be the most promising strategies for managing elevated PAI-1
      levels. Of these, TZD therapy is the only one that provides the benefits of both
      long-term glycemic control and improved cardiovascular risk profile. This article
      reviews the regulation of PAI-1, its activity in various disease states, and
      available treatment options.

PMID- 14678869
TI  - Novel actions of thiazolidinediones on vascular function and exercise capacity.
AB  - The endothelium is the first line of defense for maintaining normal vascular
      function in the vessel wall; however, the endothelium is sensitive to metabolic
      stress. In patients with insulin resistance or type 2 diabetes mellitus, a set of
      metabolic insults--namely high plasma levels of glucose and free fatty acids,
      increased inflammation, dyslipidemia, and hypertension--cause endothelial
      dysfunction and a transition from an antiatherogenic endothelium to a
      proatherogenic endothelium. Disruption of endothelial function leads to
      activation of platelets and macrophages, increased thrombotic potential,
      transition of macrophages to foam cells, stimulation of cytokine secretion, and
      proliferation of vascular smooth muscle cells. Insulin-sensitizing agents, such
      as the thiazolidinediones (TZDs), improve flow-mediated vasodilation, decrease
      macrophage and smooth muscle cell activation, proliferation, and migration, and
      decrease plaque formation. The TZDs exert multifaceted effects on the vasculature
      by regulating the expression of transcription factors and orchestrating whole
      gene programs that restore vascular physiology to the healthy state. Exercise
      training and increased levels of habitual physical activity have therapeutic
      benefit in terms of both preventing and treating insulin resistance and diabetes.
      However, this benefit of exercise training and increased physical activity is
      complicated by the fact that individuals with insulin resistance or type 2
      diabetes have decreased maximal exercise capacity or maximal oxygen consumption
      and have slower oxygen uptake kinetics at the beginning of exercise. Both of
      these abnormalities contribute to the decreased levels of habitual physical
      activity observed in patients with diabetes. Preliminary data suggest that TZDs
      improve measures of cardiac function and exercise capacity, and investigators are
      assessing the impact of treatment with rosiglitazone on exercise capacity in an
      ongoing clinical trial.

PMID- 14678870
TI  - Insulin resistance and the effects of thiazolidinediones on cardiac metabolism.
AB  - A high rate of myocardial metabolism is needed to generate energy to sustain
      cardiac contractile activity. Typically, energy generation occurs through the
      metabolism of free fatty acids (FFAs), glucose, and lactate. However, in
      individuals who are insulin resistant or who have diabetes mellitus, excessive
      FFA metabolism occurs in the heart. Pharmacologic manipulation of myocardial
      metabolism may be beneficial in these patients. There is evidence that the
      thiazolidinediones (TZDs), aside from exerting insulin-sensitizing effects on fat
      and skeletal muscles, also act on the myocardium as a result of reducing
      circulating fatty acid concentrations. Animal studies have shown that the TZDs
      influence the expression and function of glucose transporters in the heart,
      leading to improved glucose metabolism. Recent experiments have also shown that
      administration of TZDs may protect against myocardial injury associated with
      ischemia and may improve recovery of function during the postischemic period.
      This article provides a review of the potential beneficial effects of the TZDs on
      myocardial metabolism.

PMID- 14678871
TI  - Vascular reactivity and thiazolidinediones.
AB  - Endothelial dysfunction is a critical factor in the development of vascular
      disease in patients with diabetes mellitus. Maintenance of the vascular tone and
      luminal diameter of a blood vessel is dependent on the net balance of
      vasoconstrictor and vasodilator forces. In both diabetes and obesity, vascular
      reactivity is abnormal. After ischemia, carbon dioxide challenge, thermal
      challenge, or exercise, individuals with diabetes do not exhibit the increase in
      blood flow or vasodilation observed in persons without diabetes. The mechanisms
      involved in abnormal reactivity may include both the endothelium and vascular
      smooth muscle. Major vasodilator factors that act on vascular smooth muscle cells
      are nitric oxide, prostacyclin, and hyperpolarizing factor. The main
      vasoconstrictors are endothelin, angiotensin II, norepinephrine, serotonin, and
      thromboxane A(2). In patients with diabetes, there is an increase in
      vasoconstrictors and a decrease in vasodilators. Thiazolidinediones (TZDs)
      improve vasodilative responses, which may be of importance in the treatment of
      vascular disease. The TZDs have anti-inflammatory effects and suppress free fatty
      acids and reactive oxygen species at the endothelial level, which may contribute
      to the improved vascular reactivity observed in patients treated with these
      agents. In addition, these effects of TZDs may have implications for reducing the
      incidence and severity of atherosclerosis in the long term.

PMID- 14678872
TI  - Thiazolidinedione regulation of smooth muscle cell proliferation.
AB  - Vascular smooth muscle cells (VSMCs) in the media of adult arteries are normally
      quiescent, proliferate at low frequency, and are arrested in the G(0)/G(1) phase
      of the cell cycle. Proliferation of VSMCs occurs in response to arterial injury
      and plays a crucial role in the atherosclerotic process and in the pathogenesis
      of restenosis. Patients with type 2 diabetes mellitus are at increased risk for
      postangioplasty restenosis, which results from excessive intimal hyperplasia.
      Insulin sensitizers of the thiazolidinedione (TZD) class inhibit growth of VSMCs
      by attenuating the activity of important cell-cycle regulators. The TZDs inhibit
      progression from G(1) to S phase in the cell cycle by blocking growth factor
      induced phosphorylation of retinoblastoma tumor suppressor protein (Rb). In
      animal models of restenosis, TZDs inhibit intimal hyperplasia after mechanical
      injury in both insulin-sensitive and insulin-resistant vessels. Preliminary
      clinical studies using troglitazone demonstrate less intimal hyperplasia with
      this TZD after implantation of coronary stents in individuals with type 2
      diabetes. Further large trials are needed to confirm that treatment with a TZD
      can protect against postangioplasty restenosis.

PMID- 14678873
TI  - Optimal care of patients with type 2 diabetes mellitus and coronary artery
      disease.
AB  - Although cardiovascular mortality rates for the general population have declined
      during the past several decades, mortality among individuals with diabetes
      mellitus has increased. Given that the prevalence of type 2 diabetes is
      increasing dramatically and that current treatment strategies appear inadequate,
      there is a critical need for well-designed studies to address treatment of
      coronary artery disease in patients with diabetes to help guide clinical decision
      making in this setting. The Bypass Angioplasty Revascularization Investigation
      (BARI)-2D focuses on 2 specific treatment issues in the management of patients
      with type 2 diabetes. The first issue is the incremental value of early use of
      coronary revascularization procedures, and the second is the value of treating
      with an insulin-sensitizing agent versus an insulin-providing therapy. It is
      essential to determine whether treatment to enhance insulin sensitivity improves
      cardiovascular survival. Data indicate that outcomes of patients with diabetes
      and myocardial infarction are improved by administration of insulin or a regimen
      of glucose, insulin, and potassium (GIK). The Diabetes Mellitus Insulin-Glucose
      Infusion in Acute Myocardial Infarction (DIGAMI) study showed that administration
      of an insulin infusion followed by subcutaneous insulin therapy for > or =3
      months improved the long-term prognosis of diabetic patients with acute
      myocardial infarction. However, there appears to be a lack of acceptance of these
      interventions by health care providers. Clinical trials of GIK and insulin
      sensitizers are needed to define further the optimal treatment of patients with
      type 2 diabetes and cardiovascular disease.

PMID- 14678874
TI  - Endothelial function, inflammation, and prognosis in cardiovascular disease.
AB  - The vascular endothelium is an active, dynamic tissue that controls many
      important functions, including regulation of vascular tone and maintenance of
      blood circulation, fluidity, coagulation, and inflammatory responses.
      Cardiovascular risk factors affect many of the normal functions of the
      endothelium. In particular, oxidized low-density lipoprotein cholesterol
      initiates a series of events that begin with cell activation, endothelial
      dysfunction, local inflammation, and a procoagulant vascular surface. These
      conspire to result in plaque formation and ultimately plaque rupture and
      cardiovascular events. Endothelial dysfunction may be evaluated by means of
      invasive techniques, such as coronary artery reactivity to acetylcholine, or
      noninvasive techniques, such as brachial artery ultrasonography. Loss of
      endothelium-dependent vasodilation is a characteristic feature throughout the
      development of atherosclerosis, and it is independently related to future adverse
      cardiovascular risk. Therefore, measurement of endothelial function can possibly
      be used to determine risk, to triage management, and to improve outcomes. At the
      same time, inflammation is a crucial factor in the atherosclerotic disease
      process. To identify and monitor the ongoing inflammatory process, markers of
      inflammation such as C-reactive protein (CRP) have been studied. Scientific
      evidence shows that elevated plasma CRP values add to the predictive ability of
      other established risk factors; moreover, elevated values appear to augment the
      Framingham Coronary Risk Score in identifying individuals who should be
      considered for cardioprotective treatment programs. Interestingly,
      thiazolidinediones (TZDs), peroxisome proliferator-activated receptor-gamma
      agonists that are effective in the treatment of type 2 diabetes mellitus, not
      only increase insulin sensitivity but can benefit endothelial function because
      they exhibit anti-inflammatory effects. For many individuals, including those
      with the metabolic syndrome and/or type 2 diabetes, endothelial dysfunction and
      elevated plasma CRP levels indicate increased risk of cardiovascular disease.
      Notably, the TZDs have been shown to reduce CRP levels and may improve
      endothelial function.

PMID- 14678875
TI  - The patient with diabetes mellitus and heart failure: at-risk issues.
AB  - The risk for cardiovascular disease, particularly congestive heart failure, is
      significantly higher in patients with type 2 diabetes mellitus than in
      individuals without diabetes. The presence of hyperglycemia has been associated
      with changes in the myocardium that are characteristic of diabetic cardiomyopathy
      and heart failure. Furthermore, insulin resistance may be associated with
      cardiomyopathy, even in the absence of hyperglycemia, and has been linked with
      cardiovascular remodeling. The association between heart failure and insulin
      resistance suggests that agents that improve insulin sensitivity, such as the
      thiazolidinediones (TZDs), are likely to be of cardiovascular benefit in patients
      with diabetes and heart failure. Although TZDs have beneficial cardiovascular
      effects in patients with type 2 diabetes, such as reducing blood pressure,
      improving endothelial function, and exerting potential antiatherosclerotic
      effects, one must be aware of the potential of these agents to cause edema or
      weight gain as a result of fluid retention and fat accumulation. These issues are
      of particular concern in patients with diabetes who have heart failure. However,
      the glycemic and cardiovascular benefits of TZDs may outweigh the potential
      problems of weight gain and fluid retention noted in some patients. Thus the risk
      benefit ratio of using TZDs in patients who have diabetes and heart failure must
      be carefully considered in this patient population with comorbid disorders.

PMID- 14678876
TI  - Considerations for management of fluid dynamic issues associated with
      thiazolidinediones.
AB  - Thiazolidinediones (TZDs) can cause weight gain and fluid retention in some
      patients. In most cases, fluid retention is expressed as mild hemodilution. The
      incidence of clinically evident edema is relatively uncommon. In large clinical
      trials with rosiglitazone and pioglitazone, the frequency of edema in TZD-treated
      patients was about 3 to 4 times higher than in placebo-treated patients. The
      precise mechanisms responsible for weight gain, fluid retention, and edema
      associated with TZD therapy are unclear but appear to be both dose- and host
      related. Weight gain is most likely multifactorial, reflecting increased body fat
      and fluid retention. Available data are conflicting and do not completely support
      the concept that increased body weight and decreased hemoglobin/hematocrit are
      linked with evidence of fluid retention and hemodilution. As uncommon as edema
      is, new-onset heart failure is even less common in patients treated with a TZD.
      In controlled clinical trials, the frequency of congestive heart failure (CHF)
      was identical in rosiglitazone- and placebo-treated patients. The incidence of
      CHF is higher in patients receiving combination therapy with insulin and a TZD.
      Patients in the insulin-treated population who develop CHF tend to be older, have
      a longer history of type 2 diabetes mellitus, and have risk factors for heart
      failure in addition to diabetes. TZDs do not necessarily require discontinuation
      in patients who develop fluid retention or weight gain. Mild fluid retention can
      be treated by decreasing the TZD dose and/or adding a diuretic. Patients who are
      taking a TZD should be monitored for signs and symptoms of CHF, including
      excessive weight gain, edema, and dyspnea. Patients with New York Heart
      Association (NYHA) class I or II CHF can be treated with TZDs. Therapy should be
      initiated at low doses and slowly titrated to the lowest effective dose. If CHF
      worsens or becomes refractory to treatment, it may be necessary to discontinue
      the TZD. Diagnoses of NYHA class III and IV CHF were not studied in clinical
      trials of TZDs, and thus TZDs are not recommended for patients with CHF of this
      severity.

PMID- 14678877
TI  - Clinical use of thiazolidinediones: recommendations.
AB  - Type 2 diabetes mellitus is characterized by progressive beta-cell secretory
      dysfunction against a background of insulin resistance, which is present many
      years before the onset of hyperglycemia in most patients. Intensive treatment of
      diabetes reduces the risk of the onset and progression of microvascular
      complications and may impact the risk of development of macrovascular
      complications, notably coronary artery disease. Therefore, aggressive treatment
      with the goal of achieving serum glucose concentrations as close to normal as
      possible is warranted. Although medical nutritional therapy and exercise remain
      the cornerstones of therapy for type 2 diabetes, >90% of patients ultimately
      require pharmacologic therapy, and most need >1 agent to achieve therapeutic
      objectives. When considering which agent or agents to use to treat type 2
      diabetes, one must consider the mechanism of action of the drug, its ability to
      lower serum glucose concentrations, the durability of effect, and potential
      adverse effects. In addition, some medications have potential benefits that
      extend beyond glucose lowering. These include beneficial effects on the adverse
      metabolic consequences of insulin resistance and possibly beta-cell preservation.
      Thiazolidinediones should be considered as early as possible in the natural
      history of type 2 diabetes because of their persistent glucose-lowering effect
      and their ability to reduce insulin resistance as well as because these agents
      may preserve beta-cell function and reverse some of the adverse metabolic
      consequences of insulin resistance.

PMID- 14678878
TI  - [Comparative assessment of clinical efficacy of percutaneous transhepatic metal
      versus plastic biliary stent implantation for malignant biliary obstruction: a
      multi-centered investigation].
AB  - OBJECTIVE: To compare the clinical efficacy of metal versus plastic biliary stent
      implantation for treatment of malignant biliary obstruction. METHODS:
      Percutaneous transhepatic implantations of self-expandable metal stent (MS, n=61)
      or 10F plastic stent (PS, n=34) were performed in 95 patients with malignant
      biliary obstruction selected from 3 hospitals of Guangdong Province. All patients
      were followed up until death or at least one year after the procedure. Kaplan
      Meier analysis was used to compare the patients' survival and stent patency
      rates. RESULTS: The 30-day mortality rate was lower in MS group (6/61, 9.8%) than
      in PS group (9/34, 26.5%, P<0.05). The 30-day reobstruction rate and incidence of
      complications were 15.0%, 16.4% in MS group and 32.4%, 29.4% in PS group,
      respectively (P<0.01). The median patency period of the stents and median
      survival period of the patients were 230 d, 224 d in MS group and 90 d, 94 d in
      PS group, respectively (P<0.01). CONCLUSION: Metal stent implantation is superior
      to plastic stent for treatment of malignant biliary obstruction.

PMID- 14678879
TI  - [Cytoxic T lymphocyte responses to hepatitis B virus small surface antigen in
      BALB/c mice].
AB  - OBJECTIVE: To observe cytotoxic T lymphocytes (CTL) responses induced by
      immunization of mice with hepatis B small surface antigen (S-HBsAg). METHODS:
      BALB/c(H-2d) mice were injected intraperitoneally with S-HBsAg at the doses
      ranging from 0-5 microg with a booster injection 2 weeks later. Four weeks after
      the booster immunization, the specific cytotoxic reactivity of the spleen
      lymphocytes isolated from the immunized mice, following stimulation by S-HBsAg
      specific CTL epitope peptide in vitro, with 51Cr-labeled P815 cells treated with
      the peptide was observed. RESULTS: The percentage of specific release of 51Cr in
      mice immunized with S-HBsAg at the doses of 0, 0.65, 1.25, 2.5, and 5 microg was
      31.21%+/-9.23%, 42.36%+/-19.32%, 91.21%+/-22.97%, 69.25%+/-24.13% and 51.49%+/
      21.661% respectively. In mice receiving the only primary vaccination, the
      corresponding percentage was 27.34%+/-14.25%, 32.27%+/-15.35%, 56.28%+/-24.35%,
      44.34%+/-18.65% and 40.76+/-56% respectively. CONCLUSION: Immunization with S
      HBsAg efficiently elicits CTL response in BALB/c mice in a dose-dependent manner
      and enhanced by booster immunization.

PMID- 14678880
TI  - [A deletion mutant of plasminogen kringle 5 inhibits retinal capillary
      endothelial cell proliferation].
AB  - OBJECTIVE: To obtain purified deletion mutant of plasminogen kringle 5 (K5) using
      gene mutation and genetic recombination methods and assess its anti-angiogenic
      activity in vitro. METHODS: A deletion mutant of K5 was obtained by deleting 15
      amino acids from K5 while retaining all the 3 disulfide bonds. This K5 mutant
      (Mut1) was expressed in E. coli and affinity purified. The inhibition effect of
      K5 Mut1 on primary retinal capillary endothelial cells and pericytes from the
      same origin was assessed by MTT assay. RESULTS: The K5 Mut1 inhibited the
      proliferation of primary retinal capillary endothelial cells in a concentration
      dependent manner, with an apparent half-inhibition concentration (EC(50)) of
      approximately 35 nmol/L, which was 2-fold more potent than intact K5. In the same
      concentration range, this peptide did not inhibit pericytes from the same origin,
      suggesting an endothelial cell-specific inhibition. CONCLUSION: This K5 deletion
      mutant is a more potent angiogenic inhibitor than K5 and may have therapeutic
      potential in the treatment of such disorders with abnormal neovascularization as
      diabetic retinopathy, age-related macular degeneration and solid tumor.

PMID- 14678881
TI  - [Immunological effects of simultaneous injection of dexamethasone-induced
      apoptotic donor spleen cells in rats with liver transplantation].
AB  - OBJECTIVE: To study the immunological effects of simultaneous injection of
      apoptotic donor spleen cells induced by dexamethasone in rats with liver
      allotransplantation. METHODS: Four groups of rats were used in this study, each
      consisting of 10 SD rats and 10 Wistar rats with the former as the recipients and
      the latter as the donors for liver transplantation. In one of the groups, the
      recipient rats also received infusion of apoptotic spleen cells (5x10(7)) of the
      donors induced by an intraperitoneal injection of dexamethasone (at a daily dose
      of 3 mg/kg) for 3 days before liver transplantation, while in another, the
      recipient received untreated donor spleen cells. In the third group, the donor
      was treated with dexamethasone leaving the last group serving as the control
      group. The blood alanine transaminase (ALT), total bilirubin (TBil), pathological
      changes of the graft and survival time of the recipients were observed. RESULTS:
      The recipients with apoptotic donor spleen cell infusion had much higher ALT and
      TBil levels than those of the other 3 groups (P<0.05), exhibiting significantly
      shortened survival time and severer acute allograft rejection, as compared with
      the mild acute rejection in the control group (P<0.01). CONCLUSION: Simultaneous
      injection of apoptotic donor spleen cells induced by dexamethasone in rats with
      liver transplantation aggravates acute allograft rejection, one of the possible
      mechanisms of which may lie in the failure of timely removal of the apoptotic
      cells that release inflammatory factors.

PMID- 14678882
TI  - [Effect of polydatin on lipopolysaccharide-induced leucocyte chemotaxis].
AB  - OBJECTIVE: To understand the action mechanisms of polydatin (PD) in the treatment
      of septic shock in view of its effect on lipopolysaccharide (LPS)-induced
      chemotaxis of the leucocytes. METHOD: Chemotactic chamber assay was used to
      investigate the regulative role of PD in chemotaxis of the neutrophils in
      response to LPS stimulation. RESULTS: The chemotactic index of normal neutrophils
      was 4.96+/-0.69, which was significantly increased by LPS stimulation. LPS
      stimulation at the doses of 10, 100, and 1000 ng/ml resulted in the elevation of
      the chemotactic index of the neutrophils to 8.94+/-1.73, 10.31+/-1.180 and 7.12+/
      1.46 respectively (P<0.05), an effect potently reversed by the application of PD
      at the concentrations ranging from 0.008 to 0.8 mg/ml, of which 0.08 mg/ml was
      the most effective concentration that produced a decrease of the chemotactic
      index to 1.95+/-0.17. In addition, PD exhibited obvious anti-LPS effect after
      treatment for 5 to 60 min (P<0.05), while showing no influence on the chemotaxis
      of normal neutrophils (P>0.05). CONCLUSION: PD can regulate neutrophil chemotaxis
      in inflammatory reactions and may play a crucial role in the treatment of
      infections and inflammation.

PMID- 14678883
TI  - [Effects of chronic valproic acid sodium treatment and withdrawal on glutamate
      and glutamine release of C6 glioma cells].
AB  - OBJECTIVE: To determine the effects of chronic valproic acid sodium (VPA)
      treatment and subsequent withdrawal on the release of glutamate (Glu) and
      glutamine (Gln) by C6 glioma cells, so as to understand the role of Glu and Gln
      released by astrocytes in the antiepileptic mechanism of VPA and the rebound
      mechanism of VPA withdrawal. METHODS: C6 glioma cells were maintained for 2 weeks
      in DMEM medium containing 50 mg/L VPA to establish the cell model of chronic VPA
      treatment. High-performance liquid chromatography (HPLC) was performed to detect
      the levels of Glu and Gln released by C6 glioma cells after chronic VPA treatment
      and subsequent withdrawal. RESULTS: Chronic VPA treatment increased Glu release
      of C6 glioma cells, and subsequent VPA withdrawal resulted in sustained decrease
      in the Glu level, reaching the lowest level 12 h after VPA withdrawal, which was
      obviously lower than the control level. Gradual but significant increase of Glu
      level was then observed to approach the control level till 48 h after VPA
      withdrawal. For Gln release, chronic VPA treatment resulted in its decrease while
      after VPA withdrawal, gradual increase occurred to recover the control level.
      CONCLUSIONS: Chronic VPA treatment can increase Glu and decrease Gln release by
      C6 glioma cells. Glu level undergoes a rebound in response to VPA withdrawal,
      while the relatively even changes of Gln level in the same setting may not
      involve VPA withdrawal rebound mechanism.

PMID- 14678884
TI  - [Effects of flavone from leaves of Diospyros kaki on adventitial fibroblast
      proliferation induced by advanced glycation end-products in vitro].
AB  - OBJECTIVE: To observe the effects of flavone from the leaves of Diospyros kaki on
      proliferation of adventitial fibroblasts induced by advanced glycation end
      products (AGEs) in vitro. METHODS: NIH/3T3 cells cultured in vitro were treated
      with both AGEs and flavone from the leaves of Diospyros Kaki for observation in
      comparison with the cells that received treatments with either AGEs or flavone,
      or neither. The ratio of cell proliferation was determined by non-radioactive
      MTS/PES assay. RESULTS: The ratio of cell proliferation was 0.840+/-0.061 in the
      untreated control group, and was 1.330+/-0.055, 1.210+/-0.119, 1.029+/-0.076 and
      0.792+/-0.060 in AGEs groups corresponding to AGE concentrations of 100, 50, 10
      and 1 microg/ml respectively. AGEs significantly induced fibroblast proliferation
      in a dose-dependent manner when the concentration was above 10 microg/ml
      (P<0.05), as compared with the untreated control group. (P<0.05). The ratio of
      cell proliferation was 0.829+/-0.056 in cells treated with flavone at the
      concentration of 50 microg/ml, which alone failed to affect fibroblast
      proliferation (P>0.05). With AGEs stimulation, however, flavone from the leaves
      of Diospyros kaki significantly inhibited the proliferation of the fibroblasts
      (P<0.05). CONCLUSION: Flavone from the leaves of Diospyros kaki can significantly
      inhibit the proliferation of adventitial fibroblasts stimulated by AGEs in vitro.

PMID- 14678885
TI  - [Stent-based local delivery of therapeutic adenovirus effectively reduces
      neointimal proliferation in porcine coronaries].
AB  - OBJECTIVE: To find an effective means for delivering therapeutic genes of Tissue
      inhibitor of metalloproteinase-3 (TIMP-3) to the target sites of the dilated
      coronary artery for the purpose of preventing restenosis of the injured artery.
      METHODS: A stainless steel stent coated with a high-molecular-mass polymer
      phosphorylocholine, after treatment with recombinant replication-defective
      adenovirus designated as RAD TIMP-3, was implanted into the coronary arteries of
      7 pigs (therapy group). Another 7 pigs serving as the control group received
      implantation of uncoated stent. In both groups, coronary artery angiography was
      performed before withdrawal of intubation and 28 days after the implantation. For
      the purpose of planimetric analysis, the stented coronary arteries were isolated
      and fixed followed by resin embedding. Six sections were obtained for each stent
      for morphological assessment. RESULTS: The lumen diameter of the therapy group
      was 2.32+/-0.18 mm, significantly greater than that of the control group (1.79+/
      0.31 mm, P=0.014). The neointimal thickness was smaller in the therapy group
      (0.34+/-0.17 mm vs 0.81+/-0.32 mm, P=0.0 059). CONCLUSIONS: The stent with
      biosynthetic coating effectively promotes TIMP3 AdV transduction and
      transcription, which effectively reduces neointimal proliferation, thus
      confirming its role in the prevention of in-stent restenosis. This maneuver may
      offer an alternative to conventional drug coatings for preventing restenosis.

PMID- 14678886
TI  - [Analysis of T cell receptor V gamma I-J gamma gene rearrangement in elderly
      patients with acute leukemia].
AB  - OBJECTIVE: To obtain insight into the molecular mechanism of acute leukemia in
      elderly patients in relation to the clinical features of the disease. METHODS:
      DNA specimens were obtained from 34 elderly patients with acute nonlymphoblastic
      leukemia (ANLL), 9 elderly patients with acute lymphoblastic leukemia (ALL) and
      10 healthy blood donors. Polymerase chain reaction (PCR) coupled with single
      strand conformation polymorphism (SSCP) was performed to detect T cell receptor
      (TCR) V gamma I-J gamma gene rearrangement. RESULTS: In the 34 elderly ANLL
      patients, 47.1% (16/34) were found with TCRV gamma I-J gamma gene rearrangement,
      showing a higher rate of the rearrangement than in younger ANLL patients
      (P<0.025). TCRV gamma I-J gamma gene rearrangement was identified in 7 (77.8%) of
      the 9 elderly patients with ALL, and 3 of the identified cases had oligoclonal/
      subclonal rearrangement, suggesting a higher rate of oligoclonal/subclonal
      rearrangement in elderly ALL patients than in younger ALL patients (P<0.01). None
      of the blood donors was found with TCRV gamma I-J gamma gene rearrangement. The
      complete remission rate was lower in the elderly ANLL patient with TCRV gamma I-J
      gamma gene rearrangement than in those without (P<0.05). CONCLUSION: The
      detection of TCRV gamma I-J gamma gene rearrangement can be of value in assessing
      the therapeutic effect and making prognostic prediction in elderly patients with
      acute leukemia.

PMID- 14678887
TI  - [Surface morphology of CD34+ cells under atomic force microscope].
AB  - OBJECTIVE: To observe the difference in surface morphology and structure between
      CD34(+) cells from normal human subjects and from patients with leukemia.
      METHODS: Bone marrow mononuclear cells from 3 normal human subjects and 3
      patients with M2b leukemia were collected by Percoll gradient centrifugation,
      followed by purification of CD34(+) cells by means of immunomagnetic bead
      separation (MiniMAC) and examination with flow cytometry. The morphology of the
      cells were then observed with optical and atomic force microscope (AFM) in air.
      RESULTS: No significant difference was identified between the two cells under
      optical microscope. With atomic force microscope, numerous microvilli were
      observed on the surface of CD34(+) cells, and the normal cells and those from the
      leukemic patients showed significant difference in terms of the roughness of the
      cell surface. CONCLUSION: Normal CD34(+) cells have more rough and erosive
      surface structure than leukemic CD34+ cells (M2b).

PMID- 14678888
TI  - [Refolding and purification of Plasmodium falciparum glutamate dehydrogenase
      fusion protein].
AB  - OBJECTIVE: To establish the method for renaturation and purification of the
      fusion protein of Plasmodium falfiparum (FCC1/HN ) glutamate dehydrogenase (GDH)
      with glutathione S-transferase (GST). METHODS: The recombinant plasmid GDH/pGEX
      4T-1, encoding the full-length GDH gene, was transformed into E.coli BL21 (DE3)
      to achieve IPTG-induced high expression of GDH/GST in the form of inclusion
      bodies identified by SDS-PAGE. After denaturation with 8 mol/L urea, the
      inclusion bodies were subjected to 3 different renaturation methods, namely
      Sephacryl S-200 chromatography, dialysis and dilution, for refolding of the
      fusion protein. The refolded GDH/GST was then purified by different
      chromatographic approaches. RESULTS: SDS-PAGE analysis showed that the expression
      GDH/GST fusion protein mounted up to approximately 25% of the total bacterial
      protein. The dilution was better than the other two methods for the refolding of
      the fusion protein, with the optimized renaturation condition necessitating the
      presence of 20 mmol/L Tris-HCl and 1 mmol/L EDTA at pH8.5 with GSSG/GSH ratio of
      1  10, which resulted in a recovery rate exceeding 90%. Two-step ion exchange
      chromotography was optimal for purification of the fusion protein. CONCLUSION:
      The high-purity and biologically active GDH/GST can be acquired by dilution
      renaturation followed by two-step ion exchange chromatography.

PMID- 14678889
TI  - [Establishment of a mouse model of cyclophosphamide-induced thrombocytopenia and
      determination of platelet function in this model].
AB  - OBJECTIVE: To establish a mouse model of acute hematopoietic failure and explore
      the pathological basis of platelet changes in bone marrow suppression. METHODS:
      An initial large dose of cyclophosphamide (200 mg/kg) was injected through the
      tail veins of the mice, follow by daily intraperitoneal injection starting on the
      next day for 7 d. The number and morphology of the cells in the peripheral blood
      and bone marrow were observed by means of cell counting and smear, respectively,
      with the platelet aggregation determined using ADP. The coagulation time was
      measure by turbidimetry. RESULTS: The amount of platelets, erythrocytes,
      leukocytes and the nucleated cells in mice bone marrow was significantly lowered
      in the mouse models in comparison with the control mice, and the normal
      hematopoietic tissues were depressed. The blood platelets in the models were
      lowered by 49%, an amplitude of declination significantly greater than that
      occurring in the erythrocytes and leukocytes (by 28% and 25% respectively).
      Though the mean platelet volume and percent platelet aggregation underwent no
      obvious changes, the coagulation time was significantly shortened. CONCLUSION:
      The methods we described for establishing mouse models of hematopoietic failure
      induced by cyclophosphamide is rapid and highly efficient, and may facilitate
      ready preparation of mouse models of thrombocytopenia which respond strongly to
      cyclophosphamide without blood platelets function impairment.

PMID- 14678890
TI  - [Epidemiological study of the features of the index cases in SARS case clusters].
AB  - OBJECTIVE: To understand the epidemiological characteristics of the index cases
      in severe acute respiratory syndrome (SARS) cases clusters and to evaluate their
      importance in the whole epidemic process of SARS. METHODS: Data of the index SARS
      cases and the subsequent case clusters were collected by means of face-to-face
      interview in combination with field investigation and case history consultations.
      RESULTS: In all three SARS clusters, the index cases all had chronic disease and
      played the role of infection source that transmitted the virus to the patients'
      family members, attending medical staff as well as other non-SARS patients
      sharing the same ward with them. CONCLUSION: The index cases played an important
      role in transmission of SARS virus among the case clusters, and their infective
      stages are confined within certain phases of the disease course.

PMID- 14678891
TI  - [Amplification of brain-derived neurotrophic factor receptor trkB gene and
      construction of its eukaryotic expression vector].
AB  - OBJECTIVE: To construct a recombinant eukaryotic expression vector of rat brain
      derived neurotrophic factor receptor trkB gene. METHODS: Using the total RNA
      extracted from rat brain tissue as the template, the trkB gene was amplified by
      reverse transcription-polymerase chain reaction (RT-PCR) with a pair of specific
      primers containing the restriction sites of EcoRI and BamHI. The amplified
      fragment of trkB gene was digested with EcoRI and BamHI, and then subcloned into
      cloning vector pMD18-T and then expression vector pEGFP-C2. The recombinant
      plasmid was identified by restriction endonuclease analysis and PCR. RESULTS: The
      amplified DNA fragment was about 1 461 bp in length, and enzyme digestion and PCR
      analysis showed that trkB gene had been successfully cloned into the vectors
      pMD18-T and pEGFP-C2. CONCLUSION: The trkB gene of rat has been successfully
      amplified and cloned into the eukaryotic expression vector pEGFP-C2.

PMID- 14678892
TI  - [Changes of peripheral blood CD45RA+ cells after hematopoietic stem cell
      transplantation: evaluation with four-color flow cytometry].
AB  - OBJECTIVE: To investigate the alteration of peripheral blood naive T cells in
      adult patients after hematopoietic stem cell transplantation (HSCT). METHODS:
      Peripheral blood samples were collected from 49 patients requiring stem cell
      transplantation before and 15, 30, 90, and 180 d after transplantation,
      respectively. Dynamic changes of CD4(+)CD45RA(+)/CD8(+)CD45RA(+) cell counting
      were measured using flow cytometry. RESULTS: Flow cytometry results of 90 samples
      showed that CD8(+)CD45RA(+) cells recovered to normal level 30 d after
      transplantation, whereas CD4(+)CD45RA(+) cells remained low and kept a slow pace
      of gradual increase over the 6 months following the transplantation. More rapid
      recovery of the transport and regeneration function of the thymus cells was
      achieved in patients receiving hematopoietic stem cell autotransplant than in
      those with allotransplant. CONCLUSION: Measurement of the changes of
      CD4(+)CD45RA(+)/CD8(+)CD45RA(+) cell ratio using flow cytometry may provide
      insights into the molecular picture of the thymus regeneration function in
      association with immune reconstruction process in patients after stem cell
      transplantation. The number of newly generated T cells transported from the
      thymus can be a putative marker of immune reconstruction after transplantation.

PMID- 14678893
TI  - [Vertical transmission of hepatitis C virus infection].
AB  - OBJECTIVE: To investigate the mechanism for vertical transmission of hepatitis C
      virus (HCV) infection. METHODS: This study included 6 pairs of mothers and
      fetuses who were positive for anti-HCV antibody and HCV RNA, and 2 pairs of
      fathers and fetus in whom the father was positive for anti-HCV and HCV RNA while
      the mother was negative. HCV genotypes were detected by PCR and the nucleotide
      sequences of HCV genome spanning the core and envelope gene region (HCV C/E1)
      determined and compared. RESULTS: The HCV genotypes of the mothers and fetus were
      consistent. Five mother-fetus pairs were of genotype II, 1 of genotype III, with
      high homology of HCV between the mothers and their own fetuses. In contrast, in
      the two father-fetus pairs, no HCV RNA was detected in the fetuses in spite of
      the positivity of the fathers. CONCLUSION: Vertical transmission of HCV infection
      from mothers to fetus is a clinical entity.

PMID- 14678894
TI  - [Effect of simulated ischemia on activity and heterogeneity of Na+ channel in
      rabbit ventricular epicardial, midmyocardial and endocardial myocytes].
AB  - OBJECTIVE: To study the ionic mechanism of reentrant arrhythmia. METHODS: Single
      myocytes were enzymatically isolated from the epicardium, midmyocardium and
      endocardium of the left ventricle free wall of rabbit, followed by whole-cell
      patch-clamp recording of the Na(+) current (I(Na)) of the 3 cellular subtypes
      (superfused with normal and then simulated ischemia solution). The currents in
      the 3 cellular subtypes before and after simulated ischemia lasting for 10, 20,
      and 30 min, respectively, were compared. RESULTS: No changes was recorded in the
      configuration of the I-V curves and voltage dependence of I(Na) after simulated
      ischemia, and the peak I(Na) densities (- 20 mV) were significantly reduced in
      the 3 cellular subtypes compared with those recorded in normal condition. At the
      same time, the differences in I(Na) peak current densities in the 3 cellular
      subtypes underwent variations after simulated ischemia. Simulated ischemia
      resulted in obvious shift of I(Na) steady-state inactivation curves in the
      hyperpolarizing direction in the 3 cellular subtypes and inactivation was
      accelerated, and the differences in the half maximal inactivation voltages (V0.5)
      between the 3 cellular subtypes were also altered after simulated ischemia. After
      simulated ischemia, I(Na) recovery from inactivation in the epicardium,
      endocardium and midmyocardium was all slowed down in comparison with that in
      normal condition, but without statistical significance. Differences between the
      recovery curves of three cellular subtypes were noted after ischemia for 30 min.
      CONCLUSION: Ischemia can affect the activity of Na(+) channel, disrupting the
      balance of ion channel currents and the heterogeneity of I(Na) among the 3
      cellular subtypes, which is responsible for the onset of arrhythmia and partially
      explains different pharmacological reactions of the 3 cellular subtypes under
      normal and ischemic conditions.

PMID- 14678895
TI  - [Comparative study of three local ablation methods for transplanted
      hepatocellular carcinoma in mice].
AB  - OBJECTIVE: To observe the effects of three commonly used local ablation methods
      in the treatment of transplanted hepatocellular carcinoma in mice to provide
      experimental evidence for treating hepatocellular carcinoma that defies surgical
      removal. METHODS: Mouse models of hepatocellular carcinoma were established by
      means of subcutaneous transplantation, and treatment results of the three
      ablation methods, namely percutaneous ethanol injection therapy (PEIT),
      percutaneous acetic acid injection therapy (PAIT) and percutaneous local
      cryosurgery therapy (PLCT), were compared. RESULTS: The tumor inhibition rates of
      PLCT, PAIT and PEIT were 99.2%, 85.3%, and 72.8%, respectively. The rates for
      complete necrosis of the tumors were 100% (5/5), 60% (3/5), and 40% (2/5), with
      the survival time of 88.11+/-5.67, 86.67+/-7.26, and 72.89+/-12.86 days
      respectively. CONCLUSIONS: All of the three local ablation methods can inhibit
      the tumor growth to various degrees and prolong the survival time of the tumor
      bearing mice. PLCT may yield relatively better result than the other two methods.

PMID- 14678896
TI  - [Autogeneic peripheral blood hemopoietic stem cell transplantation for chronic
      myeloid leukemia with imatinib mesylate-induced negative Philadelphia
      chromosome].
AB  - OBJECTIVE: To study the possibility of curing chronic myeloid leukemia with
      autogeneic hemopoietic stem cell transplantation in patients with negative
      Philadelphia (Ph) chromosome induced by imatinib mesylate (STI 571) treatment.
      METHODS: Two patients with chronic myeloid leukemia in chronic phase, who had 90%
      Ph chromosome-positive cells and bcr/abl fusion gene-positive cells as shown by
      interphase fluorescence in situ hybridization (I-FISH), failed to respond
      favorably to interferon-alpha therapy in the treatment courses of 7 and 8 months,
      respectively. Treatment with STI 571 at a daily dose of 300 to 400 mg for 5
      months to 8 months was subsequently implemented, after which the Ph chromosome
      and bcr/abl fusion genes became normal in detection for 3 times. Peripheral blood
      haemopoietic stem cell mobilization was then initiated by intravenous injection
      of cytarabine (2.0 g/d) for 3 days, etoposide (0.2 g/d) for 3 d and
      cyclophosphamide (1.0 g/d) for one day. When the white blood cell was below
      1.0x10(9)/L, the G-CSF (300 microg/d) was administered subcutaneously for 5 or 6
      d, and the peripheral blood mononuclear cells were collected by CS3000 Plus blood
      cell separator. The percentage of bcr/abl fusion gene-positive cells among
      CD34(9) cells enriched by MiniMAC ranged from 11% to 14%. After 3 or 4 weeks, the
      patients received total body irradiation at 9 Gy given in 2 fractions, with
      intravenous injection of cyclophosphamide (60 mg/kg daily) and etoposide (300
      mg/d) for 2 d. On the day of transplantation, the collected mononuclear cells
      were 4.17x10(8)/kg and 3.9x10(8)/kg, with CD34(+)/ cells reaching
      4.89x10(6)/kg.b.w and 4.89x10(6)/kg. CsA was also used since day -1 to day +13 of
      the transplantation for prevention of graft-versus-host disease. G-CSF was
      administrated daily at the dose of 300 microg subcutaneously from day +3 to +12.
      RESULTS: After the transplantation, the absolute neutrophil count (ANC) took a
      mean of 11 d to exceed 0.5x10(9)/L in these two patients, and 19 and 21 d,
      respectively, were needed for the platelet count to exceed 20x10(9)/L. The two
      patients showed cytogenetic relapse at 120 and 300 d after the transplantation,
      respectively. CONCLUSION: Autogeneic peripheral blood stem cells transplantation
      after Ph chromosome is negative in patients with chronic myeloid leukemia, who
      receive STI 571 treatment, may also relapse, and more radical elimination of Ph
      chromosome-positive cells is needed.

PMID- 14678897
TI  - [Fluconazole resistance in Candida albicans assayed by PCR fingerprinting with
      M13 prime].
AB  - OBJECTIVE: To understand the molecular and genetic mechanism underlying
      fluconazole resistance in Candida albicans by PCR fingerprinting with M13 primer.
      METHODS: Paper disc diffusion method was employed for assay of fluconazole
      resistance in 41 clinical isolates of Candida albicans, followed by PCR
      fingerprinting with M13 primer to study the gel patterns with cluster analysis
      using neighbor joining (NJ) method performed with RAPD200 software. RESULTS: Of
      the 41 clinical isolates, 11 strains (26.8%) were fluconazole-sensitive, 8
      (19.5%) fluconazole-dependent and 22 (53.7%) fluconazole-resistance. Two to
      twelve bands could be observed among these strains, and the gel patterns revealed
      by cluster analysis were associated with the reactions of the strains against
      fluconazole and the location of infection. CONCLUSION: There is high prevalence
      of fluconazole resistance in clinical Candida albicans isolates, and PCR
      fingerprinting with M13 primer is convenient for assay of fluconazole resistance
      and molecular epidemiological study of Candida albicans.

PMID- 14678898
TI  - [Detection of peripheral blood lymphocyte subsets in treated syphilis patients
      with persistent positivity for rapid plasma reagin].
AB  - OBJECTIVE: To observe the changes in peripheral blood lymphocyte subsets in
      patients with latent syphilis after treatment, who had persistent positive
      results of test for rapid plasma reagin (RPR) and remained infectious. METHODS: T
      lymphocyte subsets and natural killer (NK) cells in peripheral blood were
      measured with flow cytometry (FCM) in these 43 patients and 30 normal subjects
      served as controls. RESULTS: Peripheral blood CD3, CD4 and NK cells exhibited no
      significant difference between the latent patients and the controls (P>0.05), but
      CD8 cells were higher in these patients (P<0.05). The treated patients with
      persistent positive RPR within two years had elevated levels of CD3, CD4 and CD8
      lymphocytes (P<0.05), but NK cells appeared to be lowered (P<0.05); in patients
      with positive RPR for over two years, CD3, CD4 and NK cells were comparable with
      those in the controls (P>0.05), but CD8 cells was elevated (P<0.05). Patients
      with RPR positivity within two years had higher CD3 and CD4 lymphocytes, but
      lower NK cells in comparison with the patients with more than two years' of
      positivity (P<0.05); CD8 cells were comparable between the two groups (P>0.05).
      CONCLUSIONS: Cellular immunity imbalance and immune suppression can be present in
      treated syphilis patients with persistent positive RPR and the risk to
      transmission, which may lower the host ability to resist and clear Treponema
      pallidum and is associated with the difficulty in treating syphilis patients and
      the persistence of positive RPR even after treatment.

PMID- 14678899
TI  - [Establishment of protein spectrum of nasopharyngeal carcinoma cell line HNE-1 by
      two-dimensional polyacrylamide gel electrophoresis].
AB  - OBJECTIVE: To establish optimized two-dimensional (2-D) polyacrylamide gel
      electrophoresis (PAGE) for displaying the full-scale protein expression spectrum
      of nasopharyngeal carcinoma (NPC) cell line HNE-1, which can be instrumental for
      proteomic study of NPC. METHODS: Large-scale HNE-1 cell culture was carried out
      from which the total protein was extracted with optimized method and separated by
      isoelectric focusing with linear and non-linear immobilized pH gradient (IPG)
      strips between different pH ranges followed by vertical SDS-PAGE. The 2-D maps of
      the proteins of HNE-1 cell line were then established. RESULTS: 2-D maps of the
      total protein of HNE-1 cell line were effectively displayed on IPG strips of
      different pH ranges and with optimized 2-D electrophoresis. CONCLUSION: With IPG
      strips with overlapping pH ranges, improvement of the protein separation can be
      achieved in 2-D electrophoresis.

PMID- 14678900
TI  - [Vector construction for the intracellular domain of human receptor for advanced
      glycation end- products and expression of the fusion protein].
AB  - OBJECTIVE: To construct a eukaryotic expression vector for GST-tagged
      intracellular domain of human receptor for advanced glycation end-products
      (hRAGE), and to study the function of the expressed fusion protein and identify
      its interacting proteins. METHODS: The coding sequence of the intracellular
      fragment of hRAGE was amplified by PCR and inserted into pGEX-KG vector, a
      general GST fusion protein expression vector. After PCR identification,
      endonuclease digestion and DNA sequencing, the recombinant was transformed into
      E.coli BL21 to achieve the expression of GST fusion protein induced by isopropyl
      beta-D-thiogalactoside (IPTG), followed by purification of the protein on
      glutathione-superflow resin. RESULTS: The recombinant of GST/hRAGE-C was
      constructed and identified by PCR, endonucleases digestion and DNA sequencing.
      After protein expression was achieved in E. coli, a molecular mass of 35 kD GST
      fusion protein was purified, whose molecular mass and purity were assessed by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). CONCLUSION:
      The expression vector for intracellular domain of hRAGE has been successfully
      constructed and efficient expression of the fusion protein is obtained, which can
      be of value for further studies.

PMID- 14678901
TI  - [Effects of open heart surgery under normothermic and hypothermic cardiopulmonary
      bypass on cytokines and complements].
AB  - OBJECTIVE: To explore the detrimental influence of normothermic and hypothermic
      cardiopulmonary bypass during open heart surgery on cytokines and complements.
      METHOD: Forty patients with congenital or rheumatic heart disease were randomized
      into 2 groups to receive normothermic cardiopulmonary bypass (CPB, study group,
      n=20) or hypothermic CPB (control group, n=20). Venous blood samples were
      respectively collected at scheduled time points preoperatively, at the end of
      CPB, and 1,4,7,14 d postoperatively to examine the level of interleukin (IL)-2,
      tumor necrosis factor (TNF)-alpha, C3, and C4. RESULTS: IL-2 in both groups
      decreased significantly at the end of CPB, postoperative day 1 and 4, but
      recovered the normal level at day 7 postoperatively. IL-2 in control group was
      significantly lower than that in the study group at each time points at the end
      of CPB and day 1 and 4 postoperatively. TNF-alpha in two groups was both elevated
      at the time points cited above, and in the study group, recovery of normal TNF
      alpha level occurred at day 7 postoperatively, whereas in the control group, the
      recovery was not achieved until postoperative day 14. C3 in the study group was
      significantly lower at the time points of the end of CPB, day 1, 7
      postoperatively than that in control group, but both elevated above normal at the
      end of CPB, day 1, and 4 postoperatively; in the study group, C3 became normal at
      day 7 postoperatively, which occurred in the control group only till day 14
      postoperatively. At the end of CPB and day 1 postoperatively, C4 was
      significantly lower in the study group than in the control group, both below the
      level measured preoperatively at the time points of the end of CPB, day 1 and 4
      postoperatively. CONCLUSION: Open-heart surgery under normothermic CPB has less
      detrimental influence on cytokines and complements than the operation under
      hypothermic CPB for better recovery of the patient.

PMID- 14678902
TI  - [Generation of neutralizing anti-interferon antibodies and factors influencing
      their production in chronic hepatitis B patients receiving recombinant interferon
      alpha treatment].
AB  - OBJECTIVE: To investigate the generation of neutralizing anti-interferon-alpha
      antibodies (NA) in patients with chronic hepatitis B in the course of interferon
      alpha treatment, and analyze the factors influencing the production of the
      antibodies. METHODS: A total of 181 patients with histologically confirmed
      chronic hepatitis B were enrolled in this study. Recombinant interferon-alpha 1b
      (rIFN-alpha 1b) was given subcutaneously 3 times a week (5 MU once) in a
      treatment course lasting for 6 to 37 months (median 10.0 months). In each case,
      serum NA was detected with antiviral neutralization bioassay, HBeAg with enzyme
      linked immunoassay (EIA) and hepatitis B virus DNA with fluorescent quantitative
      PCR every 1 to 3 months starting from 3 months after the initiation of the
      treatment. RESULTS: Of the 181 patients, 61 were positive for NA during the
      treatment course, resulting in an overall NA occurrence rate of 33.7%. The
      overall incidence rate, as well as the overall prevalence rate, was significantly
      higher in male than in female patients (39.1% vs 20.8%,   (2)=5.622, P=0.018),
      and no correlations of NA generation was observed with age, pretreatment serum
      ALT level, serum HBeAg, serum HBV DNA level, liver histological findings or
      treatment course. Binary logistic regression analysis showed that the only factor
      in relation with NA production was gender. The prevalence rates of NA varied
      significantly with the treatment courses (   (2)=98.051, P=0.000). Bivariate
      correlation analysis showed that the prevalence rate of NA, but not the incidence
      of NA, was strongly related with the treatment course (r=0.855, P<0.001).
      CONCLUSIONS: In chronic hepatitis B patients treated with rIFN-alpha 1b, the
      prevalence rate of NA, instead of the incidence of NA, is significantly related
      to the treatment course. NA was more likely to develop in male patients to
      contribute to their poorer antiviral response in comparison with the female
      patients.

PMID- 14678903
TI  - [Association of autoantibody and cytokines with latent autoimmune diabetes in
      adults].
AB  - OBJECTIVE: To assess the clinical value of detecting glutamic acid decarboxylase
      antibody (GADA), islet cell antibody (ICA) and cytokines in the diagnosis of
      latent autoimmune diabetes in adults (LADA), and define the characteristics of
      the two different types of LADA. METHODS: A total of 500 patients with an initial
      diagnosis of type 2 diabetes mellitus (T2DM) were tested for GADA, ICA and
      cytokines by enzyme-linked immunosorbent assay. RESULTS: In type 2 diabetic
      patients approximately 11% were positive for GADA, who had similar symptoms as
      hypertension, hyperlipidemia and other diabetic complications to justify the
      diagnosis of LADA-2 subtype. Another 9.6% of the total patients were ICA
      positive, and when compared with T2DM, these patients had similar clinical
      findings typical of type 1 diabetes such as younger age of onset, impaired beta
      cell function and dependence on insulin treatment. Therefore they had more
      resemblance to insulin-dependent diabetes and can be diagnosed as having LADA-1
      subtype. It was also found that cytokines positively acted on GADA and ICA,
      showing positive correlation between them. CONCLUSION: LADA has LADA-1 and LADA-2
      subtypes, and GADA, ICA and cytokines test have important clinical significance
      for diagnosis of LADA.

PMID- 14678904
TI  - [Ultrastructural changes of the skeletal muscle cells of rats subjected to
      exhausting exercises and the protective effect of vitamin E].
AB  - OBJECTIVE: To investigate the ultrastructural changes of the mitochondria in the
      skeletal muscle cells of rats subjected to repeated exhausting exercises on
      treadmill and the protective effect of oral vitamin E. METHODS: Thirty male SD
      rats were randomized into control group (n=10), exhausting exercise group (n=10)
      and exhausting exercise group with oral vitamin E treatment (n=10), with the
      latter two groups taking repeated exhausting running exercises on the treadmill
      in a course of 4 weeks. At the end of the course of exercises, the rats were
      sacrificed and the quadriceps femoris muscles isolated for observation the
      ultrastructures of the skeletal muscle cells by transmission electron microscope
      (TEM). RESULTS: After 4-week exhausting exercises, the myofilaments of the
      skeletal muscle were seen in disordered alignment, and the mitochondria exhibited
      abnormal morphological changes of swelling and vacuolar degeneration. In vitamin
      E-treated rats also undertaking the exercise, the ultrastructures of the skeletal
      muscle cells were almost normal as compared with the normal control group.
      CONCLUSION: Vitamin E can protect the function of the skeletal muscle
      mitochondria of rats taking repeated exhausting exercises.

PMID- 14678905
TI  - [Clinical study of argon laser photocoagulation for central serous
      chorioretinopathy].
AB  - OBJECTIVE: To evaluate the clinical effect of argon laser photocoagulation for
      central serous chorioretinopthy. METHODS: This study included 102 consecutive
      cases of central serous chorioretinopathy (102 eyes) with fluorescein dye leakage
      located 500 microm away from the central fovea of the macula lutea as defined by
      fundus fluorescein angiography (FFA). Argon laser photocoagulation of the leakage
      spots was performed once (98 eyes) or twice (4 eyes) with the spot diameter for
      exposure ranging from 100 to 200 microm and exposure time of 0.2 s that delivered
      energy of 80 to 150 mW. RESULTS: The visual acuity was improved in 95 cases by
      one row on the standard vision chart within 2 or 3 d after the laser treatment,
      while in the other 7 cases, the visual acuity remained unchanged. The symptoms of
      micropsia, metamorphopsia and blurred vision disappeared in 87 cases. Serous
      detachment of the sensory retina and the fovea light reflex recovered in 80 cases
      within two weeks after the treatment and no fovea injuries due to
      photocoagulation were recorded. During the follow-up lasting for 6 to 12 months
      no recurrence or long-term complications in relation with photocoagulation
      treatment were observed in these cases. CONCLUSION: Argon laser photocoagulation
      is effective for central serous choiroretinopathy, and strict control of the
      photocoagulation conditions is crucial for preventing complications in relation
      to laser coagulation.

PMID- 14678906
TI  - [Simultaneous orthotopic liver and heterotopic pancreas-duodenum transplantation
      in a diabetic patient with end-stage liver disease].
AB  - OBJECTIVE: To study the effect of combined transplantation of the liver and the
      pancreas in diabetic patients with end-stage liver disease, and explore the
      optimal surgical procedure. METHODS: Simultaneous orthotopic liver and
      heterotopic pancreas-duodenum transplantations were performed in a patient
      diagnosed as having chronic hepatitis B, hepatocirrhosis, hepatic cellular
      cancer, and insulin-dependent diabetes. Immunosuppression therapy utilized
      prednisone, tacrolimus (FK506), mycophenolate mofetil (MMF), and simulect. The
      function of the liver graft, serum amylase and lipase, blood glucose, and C
      peptide were monitored after transplantation. RESULTS: Insulin was withdrawn at
      the 6th day after operation, good liver allograft functional recovery was
      achieved, without such complications as pancreatitis, thrombosis, and localized
      infections. CONCLUSION: End-stage liver disease with concomitant insulin
      dependent diabetes is the indication for combined liver-pancreas
      transplantations, for which simultaneous orthotopic liver and heterotopic
      pancreas-duodenum transplantations may constitute the optimal surgical approaches
      as the primary choice.

PMID- 14678907
TI  - [Integrating the healthcare enterprise: an overview].
AB  - Integrating the healthcare enterprise (IHE) is a developing general norm in
      medical informatics especially in the field of radiology, which is independent of
      the manufacturers and has been accepted by a number of manufacturers and systems.
      In this paper, the authors provide a brief overview of IHE with the integration
      profiles of IHE technical framework being particularly elaborated.

PMID- 14678908
TI  - [Observation of the biological behavior of in vitro cultured immortalized
      chondrocytes induced by SV40LTAg gene transfection].
AB  - OBJECTIVE: To investigate the biological characteristics of immortalized
      chondrocytes cultured in vitro. METHODS: Primary chondrocytes were immortalized
      with SV40LTAg gene transfection and grown in monolayer culture. The biological
      characteristics of the cells were defined in terms of cell morphology and
      proliferative capacity observed under inverted microscope. GAG synthesis was
      assessed with toluidine blue and safranine O staining and type-II collagen levels
      by immunohistochemistry. RESULTS: After 50 passages, the immortalized
      chondrocytes appeared polygonal or triangular with still vigorous proliferative
      capacity in monolayer culture and positivity for GAG and collagen type II as
      characteristic of chondrocytes. CONCLUSION: The immortalized chondrocytes
      cultured in vitro can maintain their phenotype in a long term.

PMID- 14678909
TI  - [Clinical study of Photofrin photodynamic therapy for advanced cancers].
AB  - OBJECTIVE: To evaluate the clinical efficacy and adverse effects of Photofrin
      photodynamic therapy (PDT) in patients with advanced cancers. METHODS: Forty
      patients with advanced cancers in stage IV with lumen obstruction, who failed to
      respond positively to other treatment regimens, received intravenous
      administration of Photofrin as the photosensitizer at the dose of 2 mg/kg.b.w. 48
      h before PDT by 630 nm light (DIOMED) delivered through cylinder diffusing tip
      quartz fibers that passed through the biopsy channel of a flexible endoscope. PDT
      endoscopy was repeated, the necrotic tissue removed and, if necessary, the
      primary sites and other newly identified sites were subjected to a second
      exposure 8 h later. Two days after the second exposure, endoscopy was again
      performed and the necrotic tissue removed. Endoscopy was repeated one month after
      PDT and periodically thereafter as needed to treat symptomatic residual tumor.
      RESULTS: The total rate of response to the treatment was 74% in these patients,
      and the rate of lumen obstruction due to the tumors decreased from 90% to 10%
      after PDT, with significantly improved Karnofsky performance score. CONCLUSION:
      Photofrin PDT is effective and safe in the treatment of advanced cancer, which
      may relieve lumen obstruction and improve patient quality of life.

PMID- 14678910
TI  - [Clinical analysis of the relationship between injury of the marginal division
      and cognitive impairment].
AB  - OBJECTIVE: To investigate the relationship between injury in the marginal
      division (MrD) of the striatum and the cognitive impairment. METHODS: Twenty
      patients with injury in the MrD of the striatum were examined routinely by
      magnetic resonance imaging (MRI). Cognitive tests of each patient were performed
      and the results evaluated against their MRI findings. A comparative study of the
      MRI features and the degree of cognitive impairment was also performed between
      these patients and 10 patients with Alzheimer's disease (AD). RESULTS: Ischemic
      injury was the main cause of MrD injuries, manifested by abnormal signals (long
      T1 and T2 signals) in the MrD. The findings in the 10 AD patients were
      characterized by atrophy of the temporal lobe, hippocampus and the cortex. The
      average mini-mental-status examination (MMSE) score of the 20 patients was 19.7,
      with impaired memory and computation abilities as the main manifestations of
      cognitive impairments. The average MMSE score in the AD group was 11, and the
      cognitive impairments included all aspects of the cognitive function. No
      significant difference of the cognitive impairment was noted between the patients
      with only injury in the MrD and those with also the injury in other areas of the
      striatum. CONCLUSION: The MrD is probably a new area related to the memory
      function of the brain, and the injury of MrD may cause cognitive impairment.

PMID- 14678911
TI  - [Mid- to long-term effects of delayed percutaneous coronary intervention on left
      ventricular function and prognosis in patients with acute myocardial infarction].
AB  - OBJECTIVE: To investigate the mid- to long-term effects of delayed percutaneous
      coronary intervention (PCI) on the left ventricular function and clinical outcome
      of patients with acute myocardial infarction (AMI). METHODS: PCI (including
      percutaneous transluminal coronary angioplasty and stenting) was performed in 42
      patients within 1 to 2 weeks following the onset of AMI (PCI group), with another
      31 patients who were admitted within the same period to receive medication for
      AMI serving as the control group. The patients in both groups were observed for
      comparison of the occurrence of reinfarction and angina, mortality at 1 and 6
      months, and findings by ultrasound cardiograms (UCG). RESULTS: In PCI group, the
      left ventricular function were obviously improved as compared with the control
      group (P<0.01) 1 month after the onset of AMI, showing greater improvement at 6
      months (P<0.01). No death or reinfarction occurred in the PCI group, with only 1
      patients experiencing angina 5 months after PCI. In control group, death occurred
      in 2 cases, reinfarction in 1 case, recurrent angina in 4 cases (include 2 cases
      of early postinfarction angina). CONCLUSION: Delayed PCI may significantly
      improve the prognosis of patients with AMI and prolong their survival without
      cardiovascular accidents and ameliorate their left ventricular functions, with
      high success rate of the operation.

PMID- 14678912
TI  - [Experience with laparoscopic treatment of hepatic hydatid cysts].
AB  - OBJECTIVE: To summarize our experience with laparoscopic treatment of hepatic
      hydatid cysts. METHODS: A total of 120 patients with hepatic hydatid cysts who
      received laparoscopic treatment were retrospectively analyzed. RESULTS: The
      procedure was successful in all cases with no intraoperative rupture of the cysts
      or occurrence of anaphylactic shock. Among these patients, biliary fistula
      occurred in 8 cases, residual cavity effusion in 8, recurrence at other sites in
      4, and postoperative bleeding in 1 case, but all cases were cured without
      mortality. CONCLUSION: Laparoscopic treatment is safe and effective for hepatic
      hydatid cysts.

PMID- 14678913
TI  - [Chi-squared automatic interaction detection analysis and its application in
      evaluating factors attributing to Chinese university teachers' professional
      burnout].
AB  - OBJECTIVE: To introduce Chi-squared automatic interaction detection (CHAID)
      method and its application in assessment of the factors that contribute to the
      Chinese university teachers' professional burnout. METHOD: With CHAID method, the
      data acquired from a questionnaire-based investigation among 100 full-time
      teachers of Chinese universities were analyzed. RESULTS AND CONCLUSION:
      Significant difference in the attitude toward the profession was noted between
      the teachers with high- and low-level professional burnout. Among the factors
      contributing to the teachers' negative attitude, the sense of accomplishment in
      the profession, degree of preference of the profession, status of personal
      relations and social communications, along with the working environment, are the
      key elements that have most profound effect upon the teachers.

PMID- 14678914
TI  - [Study of the factors influencing the effect of the medical training of the
      students in a medical college].
AB  - By adopting epidemiologic description and comparison with known cases, the
      medical training of the students in a medical college was evaluated and the 57
      factors influencing the effect of training examined, from which 18 risk factors
      were finally identified.

PMID- 14678915
TI  - Using risk for advanced proximal colonic neoplasia to tailor endoscopic screening
      for colorectal cancer.
AB  - BACKGROUND: Colonoscopic screening for colorectal cancer has been suggested
      because sigmoidoscopy misses nearly half of persons with advanced proximal
      neoplasia. OBJECTIVE: To create a clinical index to stratify risk for advanced
      proximal neoplasia and to identify a subgroup with very low risk in which
      screening sigmoidoscopy alone might suffice. DESIGN: Cross-sectional study.
      SETTING: A company-based program of screening colonoscopy for colorectal cancer.
      PATIENTS: Consecutive persons 50 years of age or older undergoing first-time
      screening colonoscopy between September 1995 and June 2001. MEASUREMENTS: A
      clinical index with 3 variables was created from information on the first 1994
      persons. Points were assigned to categories of age, sex, and distal findings.
      Risk for advanced proximal neoplasia (defined as an adenoma 1 cm or larger or one
      with villous histology, severe dysplasia, or cancer) was measured for each score.
      The index was tested on the next 1031 persons from the same screening program.
      RESULTS: Of 1994 persons, 67 (3.4%) had advanced proximal neoplasia. A low-risk
      subgroup comprising 37% of the cohort had scores of 0 or 1 and a risk of 0.68%
      (95% CI, 0.22% to 1.57%). Among the validation group of 1031 persons, risk for
      advanced proximal neoplasia in the low-risk subgroup (comprising 47% of the
      cohort) was 0.4% (upper confidence limit of 1.49%). Application of this index
      detected 92% of persons with advanced proximal neoplasms and, if applied
      following screening sigmoidoscopy, could reduce the need for colonoscopy by 40%.
      The marginal benefit of colonoscopy among low-risk persons was small: To detect 7
      additional persons with advanced proximal neoplasia, 1217 additional
      colonoscopies would be required. CONCLUSIONS: This clinical index stratifies the
      risk for advanced proximal neoplasia and identifies a subgroup at very low risk.
      If it is validated in other cohorts or groups, the index could be used to tailor
      endoscopic screening for colorectal cancer.

PMID- 14678916
TI  - Sunscreen use and the risk for melanoma: a quantitative review.
AB  - BACKGROUND: Originally developed to protect against sunburn, sunscreen has been
      assumed to prevent skin cancer. However, conflicting reports include claims that
      sunscreen increases risk for melanoma. OBJECTIVE: To examine the strength and
      consistency of associations between melanoma and sunscreen use in the published
      literature. DATA SOURCES: A comprehensive MEDLINE search of articles published
      from 1966 to 2003 that reported information on sunscreen use and melanoma in
      humans. STUDY SELECTION: Analytic studies reporting data on sunscreen use before
      diagnosis of melanoma. DATA EXTRACTION: Two independent reviewers extracted data.
      Inconsistencies were rereviewed until agreement was achieved. When necessary, a
      third party resolved discrepancies. DATA SYNTHESIS: Odds ratios were pooled
      across studies by using standard meta-analytic techniques. Pooled odds ratios for
      ever use among 18 heterogeneous studies did not support an association between
      melanoma and sunscreen use. Variation among odds ratios was explained by studies
      that did not adjust for confounding effects of sun sensitivity. The lack of a
      dose-response effect with frequency of use (never, sometimes, or always) or years
      of use provided further evidence of a null association. CONCLUSIONS: No
      association was seen between melanoma and sunscreen use. Failure to control for
      confounding factors may explain previous reports of positive associations linking
      melanoma to sunscreen use. In addition, it may take decades to detect a
      protective association between melanoma and use of the newer formulations of
      sunscreens.

PMID- 14678917
TI  - Chest pain relief by nitroglycerin does not predict active coronary artery
      disease.
AB  - BACKGROUND: The belief that chest pain relief with nitroglycerin indicates the
      presence of active coronary artery disease is common. However, this hypothesis
      has not been tested. OBJECTIVE: To define the diagnostic and prognostic value of
      chest pain relief with nitroglycerin. DESIGN: Prospective observational cohort
      study. SETTING: Urban community teaching hospital. PATIENTS: 459 consecutive
      patients with chest pain admitted through the emergency department who received
      nitroglycerin from emergency services personnel or an emergency department nurse.
      Follow-up was obtained by telephone contact at 4 months. MEASUREMENTS: Chest pain
      relief was defined as a decrease of at least 50% in patients' self-reported pain
      within 5 minutes of the initial dose of sublingual or spray nitroglycerin. Active
      coronary artery disease was defined as any elevated serum enzyme levels, coronary
      angiography demonstrating a 70% or greater stenosis, or a positive exercise test
      result. RESULTS: Nitroglycerin relieved chest pain in 39% of patients (181 of
      459). In patients with active coronary artery disease as the likely cause of
      their chest pain, 35% (49 of 141) had chest pain relief with nitroglycerin. In
      contrast, in patients without active coronary artery disease, 41% (113 of 275)
      had chest pain relief (P > 0.2). Four-month clinical outcomes were similar in
      patients with or without chest pain relief with nitroglycerin (P > 0.2).
      CONCLUSIONS: These data suggest that, in a general population admitted for chest
      pain, relief of pain after nitroglycerin treatment does not predict active
      coronary artery disease and should not be used to guide diagnosis.

PMID- 14678918
TI  - Triage of patients with acute chest pain and possible cardiac ischemia: the
      elusive search for diagnostic perfection.
AB  - Few diagnostic decisions in medicine have been more heavily researched than the
      approach to the patient with acute chest pain. Despite the advances in both
      diagnosing and treating patients presenting with this symptom, cases of missed
      myocardial infarctions still cause substantial morbidity and mortality. This
      article examines a case in which a patient was sent home from the emergency
      department after presenting with chest pain and was subsequently found to have a
      myocardial infarction. In the context of the case, the article discusses clinical
      decision making about the diagnosis and triage of patients presenting with acute
      chest pain or with symptoms consistent with possible cardiac ischemia. A
      standardized approach to addressing the management of these patients is
      essential, given the adverse consequences of missing a life-threatening
      condition.

PMID- 14678919
TI  - Varying cost and free nicotinic acid content in over-the-counter niacin
      preparations for dyslipidemia.
AB  - BACKGROUND: Nicotinic acid is an effective treatment for dyslipidemia, but the
      content of over-the-counter niacin is not federally regulated. As a result,
      patients may use preparations of over-the-counter niacin that do not contain free
      nicotinic acid. OBJECTIVE: To characterize the types, costs, and free nicotinic
      acid content of over-the-counter niacin preparations and to review literature on
      the use of over-the-counter niacin for dyslipidemia. DATA SOURCES: Commonly used
      over-the-counter niacin preparations (500-mg tablets or capsules) from the 3
      categories of immediate-release, sustained-release, and no-flush were purchased
      at health food stores and pharmacies and from Internet-based vitamin companies.
      Pertinent literature on the use of over-the-counter niacin was obtained by
      searching PubMed. MEASUREMENTS: For each preparation studied, the monthly cost of
      therapy (at 2000 mg/d) and the free nicotinic acid content (quantified by high
      performance liquid chromatography) were reported. DATA SYNTHESIS: On average,
      immediate-release niacin preparations cost 7.10 dollars per month, sustained
      release preparations cost 9.75 dollars per month, and no-flush preparations cost
      21.70 dollars per month. The average content of free nicotinic acid was 520.4 mg
      for immediate-release niacin, 502.6 mg for sustained-release niacin, and 0 for no
      flush niacin. CONCLUSIONS: No-flush preparations of over-the-counter niacin
      contain no free nicotinic acid and should not be used to treat dyslipidemia. Over
      the-counter sustained-release niacin contains free nicotinic acid, but some
      brands are hepatotoxic. Immediate-release niacin contains free nicotinic acid and
      is the least expensive form of over-the-counter niacin.

PMID- 14678920
TI  - Update in geriatric medicine.

PMID- 14678921
TI  - Management of newly detected atrial fibrillation: a clinical practice guideline
      from the American Academy of Family Physicians and the American College of
      Physicians.
AB  - The Joint Panel of the American Academy of Family Physicians and the American
      College of Physicians, in collaboration with the Johns Hopkins Evidence-based
      Practice Center, systematically reviewed the available evidence on the management
      of newly detected atrial fibrillation and developed recommendations for adult
      patients with first-detected atrial fibrillation. The recommendations do not
      apply to patients with postoperative or post-myocardial infarction atrial
      fibrillation, patients with class IV heart failure, patients already taking
      antiarrhythmic drugs, or patients with valvular disease. The target physician
      audience is internists and family physicians dedicated to primary care. The
      recommendations are as follows: RECOMMENDATION 1: Rate control with chronic
      anticoagulation is the recommended strategy for the majority of patients with
      atrial fibrillation. Rhythm control has not been shown to be superior to rate
      control (with chronic anticoagulation) in reducing morbidity and mortality and
      may be inferior in some patient subgroups to rate control. Rhythm control is
      appropriate when based on other special considerations, such as patient symptoms,
      exercise tolerance, and patient preference. Grade: 2A. RECOMMENDATION 2: Patients
      with atrial fibrillation should receive chronic anticoagulation with adjusted
      dose warfarin, unless they are at low risk of stroke or have a specific
      contraindication to the use of warfarin (thrombocytopenia, recent trauma or
      surgery, alcoholism). Grade: 1A. RECOMMENDATION 3: For patients with atrial
      fibrillation, the following drugs are recommended for their demonstrated efficacy
      in rate control during exercise and while at rest: atenolol, metoprolol,
      diltiazem, and verapamil (drugs listed alphabetically by class). Digoxin is only
      effective for rate control at rest and therefore should only be used as a second
      line agent for rate control in atrial fibrillation. Grade: 1B. RECOMMENDATION 4:
      For those patients who elect to undergo acute cardioversion to achieve sinus
      rhythm in atrial fibrillation, both direct-current cardioversion (Grade: 1C+) and
      pharmacological conversion (Grade: 2A) are appropriate options. RECOMMENDATION 5:
      Both transesophageal echocardiography with short-term prior anticoagulation
      followed by early acute cardioversion (in the absence of intracardiac thrombus)
      with postcardioversion anticoagulation versus delayed cardioversion with pre- and
      postanticoagulation are appropriate management strategies for those patients who
      elect to undergo cardioversion. Grade: 2A. RECOMMENDATION 6: Most patients
      converted to sinus rhythm from atrial fibrillation should not be placed on rhythm
      maintenance therapy since the risks outweigh the benefits. In a selected group of
      patients whose quality of life is compromised by atrial fibrillation, the
      recommended pharmacologic agents for rhythm maintenance are amiodarone,
      disopyramide, propafenone, and sotalol (drugs listed in alphabetical order). The
      choice of agent predominantly depends on specific risk of side effects based on
      patient characteristics. Grade: 2A.

PMID- 14678922
TI  - Management of atrial fibrillation: review of the evidence for the role of
      pharmacologic therapy, electrical cardioversion, and echocardiography.
AB  - PURPOSE: This review summarizes the available evidence regarding the efficacy of
      medications used for ventricular rate control, stroke prevention, acute
      conversion, and maintenance of sinus rhythm, as well as the efficacy of
      electrical cardioversion and the use of echocardiography in patients with atrial
      fibrillation. DATA SOURCES: The Cochrane Collaboration's database of controlled
      clinical trials and MEDLINE. STUDY SELECTION: Primarily randomized, controlled
      trials of medications. DATA EXTRACTION: Paired reviewers obtained data on
      efficacy and safety. Strength of evidence was assessed. DATA SYNTHESIS: Recent
      clinical trial results showed that most patients with atrial fibrillation have
      similar outcomes with strategies for controlling ventricular rate compared with
      strategies for restoring sinus rhythm. For efficacy of primary stroke prevention,
      compared with placebo, evidence was strong for warfarin and suggestive for
      aspirin. The evidence for an increased risk for major bleeding was suggestive for
      warfarin and inconclusive for aspirin. For ventricular rate control, verapamil,
      diltiazem, atenolol, and metoprolol were qualitatively superior to digoxin and
      placebo, particularly during exercise. For efficacy of acute conversion, compared
      with placebo, evidence was strong for ibutilide, flecainide, dofetilide,
      propafenone, amiodarone, and quinidine. For efficacy of maintenance of sinus
      rhythm after conversion from atrial fibrillation, evidence was strong for
      amiodarone, propafenone, disopyramide, and sotalol. Echocardiography was found to
      be useful in estimating risk for thromboembolism and potentially useful in
      estimating likelihood of successful cardioversion and maintenance. CONCLUSIONS:
      For several key questions in the pharmacologic management of atrial fibrillation,
      strong evidence exists to support 1 or more treatment options.

PMID- 14678923
TI  - Screening sigmoidoscopy: can the road to colonoscopy be less traveled?

PMID- 14678924
TI  - Nitroglycerin: should we still ask?

PMID- 14678925
TI  - Peer review: integral to Science and indispensable to Annals.

PMID- 14678926
TI  - A Christmas story.

PMID- 14678927
TI  - A chapel for Christmas.

PMID- 14678928
TI  - Postmenopausal hormones and glycemic effects.

PMID- 14678929
TI  - Postmenopausal hormones and glycemic effects.

PMID- 14678930
TI  - Postmenopausal hormones and glycemic effects.

PMID- 14678931
TI  - Acute liver failure in the United States.

PMID- 14678932
TI  - Acute liver failure in the United States.

PMID- 14678933
TI  - Culture of Tropheryma whippelii from the vitreous fluid of a patient presenting
      with unilateral uveitis.

PMID- 14678934
TI  - Summaries for patients. Using risks to tailor screening for colorectal cancer.

PMID- 14678935
TI  - Summaries for patients. Sunscreen use and melanoma.

PMID- 14678936
TI  - Summaries for patients. Does chest pain relief with nitroglycerin mean coronary
      artery disease?

PMID- 14678937
TI  - Summaries for patients. Management of newly detected atrial fibrillation:
      recommendations from the College of Physicians and the American Academy of Family
      Physicians.

PMID- 14678938
TI  - Defibrillators and sudden death.

PMID- 14678939
TI  - Subacute painful quadriplegia and purpura.

PMID- 14678941
TI  - New approaches for studying and exploiting an old protuberance, the plant
      trichome.
AB  - BACKGROUND AND AIMS: Much recent study of plant trichomes has focused on various
      aspects of glandular secreting trichomes (GSTs) and differentiation of simple
      trichomes. This Botanical Briefing will highlight: research on various aspects
      of, and manipulation of glandular secreting trichomes; molecular aspects of the
      differentiation and development of simple trichomes of arabidopsis and cotton;
      how methods for manipulation of model systems used in the above work can be
      applied to expand our understanding of less studied surface structures of plants.
      SCOPE: The Briefing will cover: established and suggested roles of simple and
      glandular secreting trichomes; recent results regarding solute and ion movement
      in trichomes; methods for isolating trichomes; recent studies of trichome
      differentiation and development; attempts to modify metabolism in secreting
      trichomes; efforts to exploit trichomes for commercial and agronomic purposes.

PMID- 14678942
TI  - Seasonal variation of organogenetic activity and reserves allocation in the shoot
      apex of Pinus pinaster Ait.
AB  - BACKGROUND AND AIMS: To understand better the basic growth characteristics of
      pines and the fundamental properties of the shoot apical meristem (SAM),
      variations within the shoot apex of buds were studied. METHODS: A detailed
      structural comparison of meristem dimensions, organogenetic activity, and the
      presence of lipids, starch grains and tannins was performed on shoot apices of
      juvenile, and male and female adult Pinus pinaster at five different times in the
      annual growth cycle. KEY RESULTS: There were significant correlations among
      traits and differences in the pattern for juvenile and adult shoots. In juvenile
      shoots, peaks of organogenesis were present in spring and autumn, but not in
      summer. In adult shoots, one peak, characterized by an increase in meristem
      dimensions, was present in summer. The accumulation of starch grains beneath the
      SAM and of tannin in sub-apical pith parenchyma were at their maximum when
      organogenetic activity was high in spring and autumn in juvenile plants, and in
      summer in adult plants. In juvenile and adult plants, lipids were stored within
      the SAM in autumn, filling a large part of the bud in winter, and were depleted
      in the cortical parenchyma and then in the pith during shoot elongation.
      CONCLUSIONS: Depending on the sites of accumulation within the SAM and on the
      stage of the annual growth cycle, lipids, starch and tannins may be involved in
      different processes. In spring, energy and structural materials released by lipid
      hydrolysis may contribute to stem elongation and/or cell-to-cell communication.
      During organogenesis, energy and structural materials released by starch
      hydrolysis may influence developmental programmes in the SAM and adjacent cells.
      Tannins may be involved in cellular detoxification. At the end of the growing
      season, accumulation of lipid and starch is positively correlated with the onset
      of dormancy.

PMID- 14678943
TI  - Variation in the mating system of Vincetoxicum hirundinaria (Asclepiadaceae) in
      peripherial island populations.
AB  - BACKGROUND AND AIMS: Self-fertility may be selected for in small and isolated
      plant populations of normally outcrossing species. In addition, adaptations for
      self-fertility are likely to arise in island populations and in populations that
      are located at the border of the species range. The mating system of Vincetoxicum
      hirundinaria (Asclepiadaceae) is examined in island populations that are located
      at the northern border of the species range. METHODS: Pollination experiments
      were conducted under glasshouse conditions with plants from four populations. KEY
      RESULTS: The frequencies of self-fertile individuals were relatively high and did
      not differ among populations. Cross-pollination resulted in higher fruit set than
      self-pollination. However, fruit-set from self-pollination and cross-pollination
      did not differ in the self-fertile individuals. Interestingly, the proportion of
      aborted fruits was on average higher following cross-pollination than following
      self-pollination. No differences were observed in seed number or seed mass
      between self- and cross-pollinated fruits. Pollen tube growth following self- and
      cross-pollinations was indistinguishable. CONCLUSIONS: The results of this study
      revealed that V. hirundinaria possess a mixed-mating system in the studied island
      populations. Evidence was also provided for a late-acting self-incompatibility
      system commonly observed in Asclepiadaceae. No clear signs of inbreeding
      depression were observed in the early stages of development.

PMID- 14678944
TI  - From birds to humans: new concepts on airways relative to alveolar surfactant.
AB  - Pulmonary surfactant is a surface-active mixture of phospholipids and specific
      proteins that lines the epithelial surfaces of mammalian lungs. In the alveoli,
      its main function is to reduce surface tension to ensure that these structures
      can remain open during respiratory cycles of contraction and expansion. However,
      surfactant is also present in the conducting airways, even though they are
      relatively rigid and do not need a system capable of rapidly lowering surface
      tension in response to compression. This has raised the question whether there is
      a difference in composition and function between airway and alveolar surfactant.
      Interest in this question has been stimulated further by the recognition that
      surfactant also has important functions in the immune defenses of the respiratory
      tract. In this review, we describe differences that have been reported between
      human airway and alveolar surfactant. In addition, we draw parallels between
      human airway surfactant and surfactant from the lungs of birds. The latter are
      tubular and rigid and do not undergo cycles of contraction and expansion, thus
      more resembling the human conducting airways than alveoli. Using this as a model,
      we propose a new hypothesis to explain structural and functional differences
      between human airway and alveolar surfactant. We suggest that the molecular
      composition of surfactant is adapted to differences in the architecture of
      pulmonary surfaces and to the dynamics of surface area changes during
      respiration.

PMID- 14678945
TI  - Bid activation in kidney cells following ATP depletion in vitro and ischemia in
      vivo.
AB  - Bid is a proapoptotic Bcl-2 family protein, which on activation translocates to
      mitochondria and induces damage to the organelles. Activation of Bid depends on
      its proteolytic processing into truncated forms of tBid. Bid is highly expressed
      in the kidneys; however, little is known about its role in renal pathophysiology.
      In this study, we initially examined Bid activation in cultured rat kidney
      proximal tubular cells following ATP depletion. The cells were depleted of ATP by
      azide incubation in the absence of metabolic substrates and then returned to
      normal culture medium for recovery. Typical apoptosis developed during recovery
      of ATP-depleted cells. This was accompanied by Bid cleavage, releasing tBid of 15
      and 13 kDa. Bid cleavage was abolished in cells overexpressing Bcl-2, an
      antiapoptotic gene. It was also suppressed by caspase inhibitors. Peptide
      inhibitors of caspase-9 were more effective in blocking Bid cleavage compared
      with inhibitors of caspase-8 and caspase-3. Provision of glucose, a glycolytic
      substrate, during azide incubation inhibited Bid cleavage as well, indicating
      that Bid cleavage was initiated by ATP depletion. Consistently, Bid cleavage was
      also induced following ATP depletion by hypoxia or mitochondrial uncoupling. Of
      significance, cleaved Bid translocated to mitochondria, suggesting a role for Bid
      in the development of mitochondrial defects in ATP-depleted cells. Finally, Bid
      cleavage was induced during renal ischemia-reperfusion in the rat. Together,
      these results provide the first evidence for Bid activation in kidney cells
      following ATP depletion in vitro and renal ischemia in vivo.

PMID- 14678946
TI  - Kinetics and regulation of a Ca2+-activated Cl- conductance in mouse renal inner
      medullary collecting duct cells.
AB  - Using the whole cell patch-clamp technique, a Ca2+-activated Cl- conductance
      (CaCC) was transiently activated by extracellular ATP (100 microM) in primary
      cultures of mouse inner medullary collecting duct (IMCD) cells and in the mouse
      IMCD-K2 cell line. ATP also transiently increased intracellular Ca2+
      concentration ([Ca2+]i) from 100 nM to peak values of approximately 750 nM in
      mIMCD-K2 cells, with a time course similar to the ATP-induced activation and
      decay of the CaCC. Removal of extracellular Ca2+ had no major effect on the peak
      Cl- conductance or the increase in [Ca2+]i induced by ATP, suggesting that Ca2+
      released from intracellular stores directly activates the CaCC. In mIMCD-K2
      cells, a rectifying time- and voltage-dependent current was observed when [Ca2+]i
      was fixed via the patch pipette to between 100 and 500 nM. Maximal activation
      occurred at approximately 1 microM [Ca2+]i, with currents losing any kinetics and
      displaying a linear current-voltage relationship. From Ca2+-dose-response curves,
      an EC50 value of approximately 650 nM at -80 mV was obtained, suggesting that
      under physiological conditions the CaCC would be near fully activated by mucosal
      nucleotides. Noise analysis of whole cell currents in mIMCD-K2 cells suggests a
      single-channel conductance of 6-8 pS and a density of approximately 5,000
      channels/cell. In conclusion, the CaCC in mouse IMCD cells is a low-conductance,
      nucleotide-sensitive Cl- channel, whose activity is tightly coupled to changes in
      [Ca2+]i over the normal physiological range.

PMID- 14678947
TI  - Angiotensin II blockade prevents hyperglycemia-induced activation of JAK and STAT
      proteins in diabetic rat kidney glomeruli.
AB  - Clinical and animal studies show that treatment with angiotensin-converting
      enzyme (ACE) inhibitors or ANG II-receptor antagonists slows progression of
      nephropathy in diabetes, indicating ANG II plays an important role in its
      development. We previously reported that hyperglycemia augments both ANG II
      induced growth and activation of Janus kinase (JAK)2 and signal transducers and
      activators of transcription (STAT) proteins in cultured rat mesangial cells.
      Furthermore, we demonstrated that the tyrosine kinase enzyme JAK2 plays a key
      role in both ANG II- and hyperglycemia-induced growth in these cells. We
      hypothesized that the ACE inhibitor captopril and the ANG II-receptor antagonist
      candesartan would hinder hyperglycemic-induced activation of JAK and STAT
      proteins in rat glomeruli, demonstrating that ANG II plays an important role in
      the activation of these proteins in vivo. Adult male Sprague-Dawley rats were
      given either streptozotocin (STZ; 60 mg/kg iv) or vehicle, and glomeruli were
      isolated 2 wk later. Activation of JAK and STAT proteins was evaluated by Western
      blot analysis for specific tyrosine phosphorylation. Groups of rats were given
      captopril (75-85 mg x kg(-1) x day(-1)), candesartan (10 mg x kg(-1) x day(-1)),
      or the JAK2 inhibitor AG-490 (5 mg x kg(-1) x day(-1)) for the study's duration.
      STZ stimulated glomerular phosphorylation of JAK2, STAT1, STAT3, and STAT5.
      Phosphorylation was reduced in rats treated with captopril, candesartan, and AG
      490. Furthermore, both candesartan and AG-490 inhibited STZ-induced increases in
      urinary protein excretion. In conclusion, our studies demonstrate that
      hyperglycemia induces activation of JAK2 and the STATs in vivo via an ANG II
      dependent mechanism and that these proteins may be involved in the early kidney
      damage associated with diabetes.

PMID- 14678949
TI  - Expression and relative abundance of short transient receptor potential channels
      in the rat renal microcirculation.
AB  - In the resistance vessels of the renal microcirculation, store- and/or receptor
      operated calcium entry contribute to the rise in vascular smooth muscle cell
      (VSMC) intracellular calcium concentration in response to vasoconstrictor
      hormones. Short transient receptor potential (TRPC) channels are widely expressed
      in mammalian tissues and are proposed mediators of voltage-independent cation
      entry in multiple cell types, including VSMCs. The seven members of the TRPC gene
      family (TRPC1-7) encode subunit proteins that are thought to form homo- and
      heterotetrameric channels that are differentially regulated depending on their
      subunit composition. In the present study, we demonstrate the relative abundance
      of TRPC mRNA and protein in freshly isolated rat renal resistance vessels,
      glomeruli, and aorta. TRPC1, 3, 4, 5, and 6 mRNA and protein were detected in
      both renal resistance vessels and aorta, whereas TRPC2 and TRPC7 mRNA were not
      expressed. TRPC1, 3, 5, and 6 protein was present in glomeruli. TRPC3 and TRPC6
      protein levels were significantly greater in the renal resistance vessels, about
      six- to eightfold higher than in aorta. These data suggest that TRPC3 and TRPC6
      may play a role in mediating voltage-independent calcium entry in renal
      resistance vessels that is functionally distinct from that in aorta.

PMID- 14678950
TI  - Dual constrictor and dilator actions of ET(B) receptors in the rat renal
      microcirculation: interactions with ET(A) receptors.
AB  - The vascular actions of endothelin-1 (ET-1) reflect the combination of
      vasoconstrictor ET(A) and ET(B) receptors on smooth muscle cells and vasodilator
      ET(B) receptors on endothelial cells. The present study investigated the
      contribution of ET receptor subtypes using a comprehensive battery of agonists
      and antagonists infused directly into the renal artery of anesthetized rats to
      evaluate the actions of each receptor class alone and their interactions. ET-1 (5
      pmol) reduced renal blood flow (RBF) 25+/-1%. ET(A) antagonist BQ-123 attenuated
      this response to a 15+/-1% decrease in RBF (P < 0.01), indicating net
      constriction by ET(B) receptors. Combined receptor blockade (BQ-123+BQ-788)
      resulted in a renal vasoconstriction of 7+/-1% (P = 0.001 vs. BQ-123), supporting
      a constrictor action of ET(B) receptors. In marked contrast, the ET(B) antagonist
      BQ-788 enhanced the ET-1 RBF response to 60+/-5% (P < 0.001), suggesting ET(B)
      mediated net dilation. Consistent with ET(A) blockade, the ET(B) agonist
      sarafotoxin 6C (S6C) produced vasoconstriction, reducing RBF by 23+/-5%. Dose
      response curves for ET-1 and S6C showed similar degrees of constriction between
      0.2 and 100 pmol. Both antagonists (BQ-123, BQ-788) were equally effective at
      threefold lower than the standard doses, suggesting complete inhibition. We
      conclude that ET(B) receptors alone exert a net constrictor effect but cause a
      net dilator influence when costimulated with ET(A) receptors. Such opposing
      actions indicate more complex than additive interaction between receptor
      subtypes. Model analysis suggests ET(A)-mediated constriction is appreciably
      greater without than with costimulation of ET(B) receptors. Possible explanations
      include ET-1 clearance by ET(B) receptors and/or a dilator ET(B) receptor
      function that counteracts constriction.

PMID- 14678951
TI  - Retention of estradiol negative feedback relationship to LH predicts ovulation in
      response to caloric restriction and weight loss in obese patients with polycystic
      ovary syndrome.
AB  - The present study tests the hypothesis that specific endocrine, metabolic, and
      anthropometric features distinguish obese women with polycystic ovary syndrome
      (PCOS) who resume ovulation in response to calorie restriction and weight loss
      from those who do not. Fifteen obese (body mass index 39 +/- 7 kg/m(2))
      hyperandrogenemic oligoovulatory patients undertook a very low calorie diet
      (VLCD), wherein each lost > or =10% of body weight over a mean of 6.25 mo. Body
      fat distribution was quantitated by magnetic resonance imaging. Hormones were
      measured in the morning at baseline, after 1 wk of VLCD, and after 10% weight
      loss. To monitor LH release, blood was sampled for 24 h at 10-min intervals
      before intervention and after 7 days of VLCD. Responders were defined a priori as
      individuals exhibiting two or more ovulatory cycles in the course of
      intervention, as corroborated by serum progesterone concentrations > or =18
      nmol/l followed by vaginal bleeding. At baseline, responders had a higher sex
      hormone-binding globulin (SHBG) concentration but were otherwise
      indistinguishable from nonresponders. Body weight, the size of body fat depots,
      and plasma insulin levels declined to a similar extent in responders and
      nonresponders. Also, SHBG increased, and the free testosterone index decreased
      comparably. However, responders exhibited a significant decline of circulating
      estradiol concentrations (from 191 +/- 82 to 158 +/- 77 pmol/l, means +/- SD, P =
      0.037) and a concurrent increase in LH secretion (from 104 +/- 42 to 140 +/- 5
      U.l(-1).day(-1), P = 0.006) in response to 7 days of VLCD, whereas neither
      parameter changed significantly in nonresponders. We infer that evidence of
      retention of estradiol-dependent negative feedback on LH secretion may forecast
      follicle maturation and ovulation in obese patients with PCOS under dietary
      restriction.

PMID- 14678952
TI  - Exercise augments the acute anabolic effects of intradialytic parenteral
      nutrition in chronic hemodialysis patients.
AB  - Decreased dietary protein intake and hemodialysis (HD)-associated protein
      catabolism are among several factors that predispose chronic hemodialysis (CHD)
      patients to uremic malnutrition and associated muscle wasting. Intradialytic
      parenteral nutrition (IDPN) acutely reverses the net negative whole body and
      forearm muscle protein balances observed during the HD procedure. Exercise has
      been shown to improve muscle protein homeostasis, especially if performed with
      adequately available intramuscular amino acids. We hypothesized that exercise
      performance would provide additive anabolic effects to the beneficial effects of
      IDPN. We studied six CHD patients at two separate HD sessions: 1) IDPN
      administration only and 2) IDPN + exercise. Patients were studied 2 h before,
      during, and 2 h after an HD session by use of a primed constant infusion of l-[1
      (13)C]leucine and l-[ring-(2)H(5)] phenylalanine. Exercise combined with IDPN
      promoted additive twofold increases in forearm muscle essential amino acid uptake
      (455 +/- 105 vs. 229 +/- 38 nmol.100 ml(-1).min(-1), P < 0.05) and net muscle
      protein accretion (125 +/- 37 vs. 56 +/- 30 microg.100 ml(-1).min(-1), P < 0.05)
      during HD compared with IDPN alone. Measurements of whole body protein
      homeostasis and energy expenditure were not altered by exercise treatment. In
      conclusion, exercise in the presence of adequate nutritional supplementation has
      potential as a therapeutic intervention to blunt the loss of muscle mass in CHD
      patients.

PMID- 14678953
TI  - Islet cell engraftment and control of diabetes in rats after transplantation of
      pig pancreatic anlagen.
AB  - The insufficient supply of tissue, loss posttransplantation, and limited
      potential for expansion of beta-cells restrict the use of islet
      allotransplantation for diabetes. A way to overcome the supply and expansion
      problems is to xenotransplant embryonic tissue. We have shown that whole rat
      pancreatic anlagen isotransplanted into the omentum of rats, or xenotransplanted
      into costimulatory blocked mice, undergo growth and differentiate into islets
      surrounded by stoma without exocrine tissue. Isotransplants normalize glucose
      tolerance in diabetic hosts. Here, we show that embryonic day 29 porcine pancreas
      transplanted into the omentum of adult diabetic rats undergoes endocrine tissue
      differentiation over 20 wk and normalizes body weights and glucose tolerance.
      Unlike rat-to-rodent transplants, individual alpha- and beta-cells engraft
      without a stromal component, and no immunosuppression is required for pig-to-rat
      transplants. Herein is described a novel means to effect the xenotransplantation
      of individual islet cells across a highly disparate barrier.

PMID- 14678954
TI  - Gastric inhibitory polypeptide does not inhibit gastric emptying in humans.
AB  - The insulinotropic gut hormone gastric inhibitory polypeptide (GIP) has been
      demonstrated to inhibit gastric acid secretion and was proposed to possess
      "enterogastrone" activity. GIP effects on gastric emptying have not yet been
      studied. Fifteen healthy male volunteers (23.9 +/- 3.3 yr, body mass index 23.7
      +/- 2.3 kg/m(2)) were studied with the intravenous infusion of GIP (2 pmol.kg(
      1).min(-1)) or placebo, each administered to the volunteers on separate occasions
      from -30 to 360 min in the fasting state. At 0 min, a solid test meal (250 kcal
      containing [(13)C]sodium octanoate) was served. Gastric emptying was calculated
      from the (13)CO(2) exhalation rates in breath samples collected over 360 min.
      Venous blood was drawn in 30-min intervals for the determination of glucose,
      insulin, C-peptide, and GIP (total and intact). Statistical calculations were
      made by use of repeated-measures ANOVA and one-way ANOVA. During the infusion,
      GIP rose to steady-state concentrations of 159 +/- 15 pmol/l for total and 34 +/-
      4 pmol/l for intact GIP (P < 0.0001). Meal ingestion further increased GIP
      concentrations in both groups, reaching peak levels of 265 +/- 20 and 82 +/- 9
      pmol/l for total and 67 +/- 7 and 31 +/- 9 pmol/l for intact GIP during the
      administration of GIP and placebo, respectively (P < 0.0001). There were no
      differences in glucose, insulin, and C-peptide between the experiments with the
      infusion of GIP or placebo. Gastric half-emptying times were 120 +/- 9 and 120 +/
      18 min (P = 1.0, with GIP and placebo, respectively). The time pattern of
      gastric emptying was similar in the two groups (P = 0.98). Endogenous GIP
      secretion, as derived from the incremental area under the curve of plasma GIP
      concentrations in the placebo experiments, did not correlate to gastric half
      emptying times (r(2) = 0.15, P = 0.15 for intact GIP; r(2) = 0.21, P = 0.086 for
      total GIP). We conclude that gastric emptying does not appear to be influenced by
      GIP. The secretion of GIP after meal ingestion is not suppressed by its exogenous
      administration. The lack of effect of GIP on gastric emptying underlines the
      differences between GIP and the second incretin glucagon-like peptide 1.

PMID- 14678955
TI  - Selective cytokine inhibitory drugs with enhanced antiangiogenic activity control
      tumor growth through vascular inhibition.
AB  - Selective cytokine inhibitory drugs (SelCIDs) are a novel class of
      phosphodiesterase 4 inhibitors discovered during a thalidomide analog discovery
      program. These analogs were evaluated for their ability to inhibit tumor
      angiogenesis, vascularity, and growth. Two analogs (CC-7034 and CC-9088) were
      identified that had enhanced antiangiogenic activity in Matrigel assays compared
      with parental thalidomide. These analogs also inhibited the growth of established
      K1735 and RENCA murine tumors. Tumors whose growth was suppressed by SelCID
      treatment exhibited decreased vessel density together with increased tumor cell
      hypoxia and death. The decrease in vascularity produced by SelCID treatment is
      attributed to a selective loss of vessels devoid of pericyte coverage, suggesting
      that these agents target immature tumor vessels. That tumor cell death was
      localized to relatively avascular or hypoxic areas, coupled with the fact that
      none of the analogs was cytotoxic in vitro against the tumor cells, demonstrates
      that these analogs are novel antivascular agents with potent antitumor activity.

PMID- 14678956
TI  - Overexpression of the oncogenic kinase Pim-1 leads to genomic instability.
AB  - Aneuploidy and chromosomal aberrations are hallmarks of most human epithelial
      malignancies. Here we show that overexpression of the oncogenic kinase Pim-1 in
      human prostate epithelial cells induces genomic instability by subverting the
      mitotic spindle checkpoint. Cells overexpressing Pim-1 have a defect in the
      mitotic spindle checkpoint, abnormal mitotic spindles, centrosome amplification,
      and chromosome missegregation. Polyploidy and aneuploidy ensue due to a delay in
      completing cytokinesis. These results define a novel role for elevated Pim-1
      expression in promoting genomic instability in human prostate tumors.

PMID- 14678957
TI  - Up-regulation of fibroblast growth factor-binding protein, by beta-catenin during
      colon carcinogenesis.
AB  - Fibroblast growth factor-binding protein (FGF-BP) releases immobilized FGFs from
      the extracellular matrix and can function as an angiogenic switch molecule in
      cancer. Here we show that FGF-BP is up-regulated in early dysplastic lesions of
      the human colon that are typically associated with a loss of adenomatous
      polyposis coli and up-regulation of beta-catenin. In addition, FGF-BP expression
      is induced in dysplastic lesions in ApcMin/+ mice in parallel with the up
      regulation of beta-catenin. Also, in cell culture studies FGF-BP is induced by
      beta-catenin through direct activation of the FGF-BP gene promoter. We conclude
      that FGF-BP is a target gene of beta-catenin.

PMID- 14678958
TI  - Gamma-aminobutyric acid as a promoting factor of cancer metastasis; induction of
      matrix metalloproteinase production is potentially its underlying mechanism.
AB  - We investigated expression of gamma-aminobutyric acid (GABA), glutamate
      decarboxylase, and matrix metalloproteinase (MMP) in the prostates of patients
      with cancer or benign prostatic hypertrophy by immunohistochemical study. Marked
      expression of GABA, glutamate decarboxylase 67, and MMPs was observed in the
      prostates of cancer patients with metastasis (n = 72) and lymph node metastasis,
      although only sparse expression was noted in those of cancer patients without
      metastasis (n = 76) or patients with benign prostatic hypertrophy (n = 152). We
      then investigated the influence of GABA stimulation on in vitro MMP production
      and the invasive ability of cancer cells using human prostate cancer cell line C4
      2. The production of MMPs increased significantly in cancer cells after a 24-h
      incubation with GABA. Cell invasion assay using a BioCoat Matrigel Invasion
      Chamber kit revealed that GABA stimulation significantly promoted the invasive
      ability of cancer cells and that addition of MMP inhibitor GM6001 significantly
      decreased GABA-induced migration. This may indicate the involvement of MMP
      activity in GABA-induced cancer cell invasion. We further analyzed the
      transmission pathway by performing GABA receptor modulation. The GABA(B) receptor
      agonist baclofen significantly increased MMP production as well as invasive
      ability. Moreover, blockade of the GABA(B) receptor pathway using GABA(B)
      receptor antagonist CGP 35348 significantly inhibited GABA-induced MMP production
      and invasive ability in cancer cells, whereas GABA(A) receptor modulation did not
      influence MMP production or the invasive ability of cancer cells. Thus, increased
      expression of GABA may be implicated in cancer metastasis by promoting MMP
      production in cancer cells, and the GABA(B) receptor pathway may be involved in
      the process.

PMID- 14678959
TI  - Glutathione S-transferase pi amplification is associated with cisplatin
      resistance in head and neck squamous cell carcinoma cell lines and primary
      tumors.
AB  - PURPOSE: The purpose is to evaluate the association of glutathione S-transferase
      pi (GST-pi) amplification and cisplatin resistance in head and neck cancer.
      EXPERIMENTAL DESIGN: An analysis of chromosomal abnormalities in 10 head and neck
      cancer cell lines by comparative genomic hybridization was performed. GST-pi
      amplification and expression were evaluated in head and neck cell lines and
      paraffin-embedded tissue by fluorescence in situ hybridization (FISH) and
      immunohistochemistry. RESULTS: Changes in the DNA copy number were seen in all 10
      cell lines by comparative genomic hybridization. The most frequent chromosomal
      alterations were: gain at 3q; loss at 3p; gain at 8q; loss of 18q; gain at 20q;
      loss at 8p; and gain of 11q11-q13. Using FISH, 9 of 10 cell lines showed
      increased GST-pi copy number. GST-pi amplification was detected in 7 of 10 cell
      lines. Five were relatively cisplatin resistant, and 2 were relatively cisplatin
      sensitive (mean IC(50), 11.2 and 2.75 microM). Two relatively cisplatin-sensitive
      cell lines showed GST-pi gain and another relatively cisplatin-sensitive cell
      line had predominantly two copies of the gene. In 10 tumor specimens, 4 had two
      copies of GST-pi. All 4 had a complete response to neoadjuvant chemotherapy, 3 of
      whom are alive >50 months from treatment compared with 2 patients showing GST-pi
      amplification. Neither responded to chemotherapy, and both died of disease <9
      months from diagnosis. CONCLUSIONS: Using FISH, GST-pi amplification is a common
      event in head and neck squamous cell carcinoma and may be associated with
      cisplatin resistance and poor clinical outcomes in head and neck cancer patients
      treated with cisplatin-based therapy.

PMID- 14678960
TI  - Subcellular localization of activating transcription factor 2 in melanoma
      specimens predicts patient survival.
AB  - The transcription factor activating transcription factor 2 (ATF2) has been shown
      to be associated with melanocytic oncogenesis and melanoma tumor proliferation in
      preclinical models. The clinical significance of ATF2 expression is unknown. To
      determine the prognostic value of ATF2 in melanoma, we evaluated the pattern and
      level of ATF2 expression in a large cohort of melanoma specimens.
      Immunohistochemical staining was performed on a tissue microarray representing
      544 patients with a mean follow-up time of 60 months. Expression was evaluated
      semiquantitatively and correlated with overall survival and other
      clinicopathological data. Strong cytoplasmic ATF2 expression was associated with
      primary specimens rather than metastases (P < 0.0001) and with better survival (P
      = 0.0003). Strong nuclear ATF2 expression was associated with metastatic
      specimens (P < 0.0001) and with poor survival (P = 0.0008). Patients who had both
      weak cytoplasmic and strong nuclear ATF2 staining had the worst outcome, both
      among the full cohort of patients (P < 0.0001) and among the patients with
      localized disease (n = 269; P < 0.0001). On multivariate analysis of the primary
      cutaneous specimens, weak cytoplasmic staining and strong nuclear staining was an
      independent predictor of poor outcome, as was Clark level. Nuclear ATF2 is likely
      to be transcriptionally active, whereas cytoplasmic ATF2 probably represents an
      inactive form. These findings support other preclinical findings in which
      transcriptionally active ATF2 is involved in tumor progression-proliferation in
      melanoma. Moreover, our findings suggest that ATF2 might be a useful prognostic
      marker in early-stage melanoma.

PMID- 14678961
TI  - FGFR3 and TP53 gene mutations define two distinct pathways in urothelial cell
      carcinoma of the bladder.
AB  - FGFR3 and TP53 mutations are frequent in superficial papillary and invasive
      disease, respectively. We used denaturing high-performance liquid chromatography
      and sequencing to screen for FGFR3 and TP53 mutations in 81 newly diagnosed
      urothelial cell carcinomas. Tumors were classified as follows: 31 pTa, 1
      carcinoma in situ, 30 pT1, and 19 pT2-T4. Tumor grades were as follows: 10 G1, 29
      G2, and 42 G3. FGFR3 mutations were associated with low-stage (P < 0.0001), low
      grade (P < 0.008) tumors, whereas TP53 mutations were associated with high-stage
      (P < 0.003), high-grade (P < 0.02) tumors. Mutations in these two genes were
      almost mutually exclusive. Our results suggest that FGFR3 and TP53 mutations
      define separate pathways at initial diagnosis of urothelial cell carcinoma.

PMID- 14678962
TI  - Differential killing of mismatch repair-deficient and -proficient cells: towards
      the therapy of tumors with microsatellite instability.
AB  - DNA mismatch repair (MMR) defects bring about a strong mutator phenotype and
      microsatellite instability (MSI). In an attempt to exploit MSI in cancer therapy,
      we constructed expression vectors carrying a thymidine kinase/blasticidin
      deaminase fusion gene downstream from a (C)(12) or an (A)(26) microsatellite and
      stably transfected these constructs into human cells in which the MMR status
      could be regulated by doxycycline. We now show that ganciclovir-resistant clones
      arising through frameshifts in the (C)(12) microsatellite were 20 times more
      frequent in cells in which MMR was inactivated. This difference may be exploited
      in gene therapy of tumors with MSI, which represent a substantial proportion of
      cancers of many different tissues.

PMID- 14678963
TI  - Cancer prevention by tea polyphenols is linked to their direct inhibition of
      antiapoptotic Bcl-2-family proteins.
AB  - Epidemiological data and in vitro studies on cancer chemoprevention by tea
      polyphenols have gained attention recently from the scientific community,
      nutritionists, the pharmaceutical industry, and the public. Despite the several
      efforts made recently to elucidate the molecular basis for the anticancer
      activity of these natural products, little correlation has been found thus far
      between the putative protein targets of compounds found in tea extracts and
      levels found in plasma after tea consumption. Here, by using a combination of
      nuclear magnetic resonance binding assays, fluorescence polarization assay, and
      computational docking studies, we found that certain green tea catechins and
      black tea theaflavins are very potent inhibitors (K(i) in the nanomolar range) of
      the antiapoptotic Bcl-2-family proteins, Bcl-x(L) and Bcl-2. These data suggest a
      strong link between the anticancer activities of these tea polyphenols and their
      inhibition of a crucial antiapoptotic pathway, which is implicated in the
      development of many human malignancies.

PMID- 14678964
TI  - A multimodal nanoparticle for preoperative magnetic resonance imaging and
      intraoperative optical brain tumor delineation.
AB  - The determination of brain tumor margins both during the presurgical planning
      phase and during surgical resection has long been a challenging task in the
      therapy of brain tumor patients. Using a model of gliosarcoma with stably green
      fluorescence protein-expressing 9L glioma cells, we explored a multimodal (near
      infrared fluorescent and magnetic) nanoparticle as a preoperative magnetic
      resonance imaging contrast agent and intraoperative optical probe. Key features
      of nanoparticle metabolism, namely intracellular sequestration by microglia and
      the combined optical and magnetic properties of the probe, allowed delineation of
      brain tumors both by preoperative magnetic resonance imaging and by
      intraoperative optical imaging. This prototypical multimodal nanoparticle has
      unique properties that may allow radiologists and neurosurgeons to see the same
      probe in the same cells and may offer a new approach for obtaining tumor margins.

PMID- 14678965
TI  - Photodynamic therapy: a means to enhanced drug delivery to tumors.
AB  - Using the photosensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a, we
      have determined that photodynamic therapy (PDT) can be used to facilitate the
      delivery of macromolecular agents. PDT regimens that use low fluences and fluence
      rates were the most successful. This effect was demonstrated for fluorescent
      microspheres with diameters ranging from 0.1 to 2 microm. Such treatment given
      immediately before administration of Doxil, a liposomally encapsulated
      formulation of doxorubicin with an average diameter of 0.1 microm, significantly
      enhanced its accumulation in transplanted murine Colo 26 tumors. The combination
      of PDT and Doxil led to a highly significant potentiation in tumor control
      without concomitant enhancement of systemic or local toxicity. Interestingly,
      concentration-effect modeling suggested that the enhanced cure rate was greater
      than what was predicted based on the increase in intratumor Doxil concentration.
      In summary, we have developed a novel PDT treatment that enhances the delivery
      and efficacy of macromolecule-based cancer therapies such as Doxil.

PMID- 14678966
TI  - Functional analysis of mutations within the kinase activation segment of B-Raf in
      human colorectal tumors.
AB  - Mutations in the B-Raf gene have been reported in a number of human cancers,
      including colorectal carcinoma. More than 80% of the B-Raf mutations were V599E.
      Although other mutations have been reported, their functional consequences were
      unclear. Here, we examined the effect of colon tumor-associated B-Raf mutations
      within the kinase activation segment, including V599E, on extracellular signal
      regulated kinase (Erk) and nuclear factor kappaB (NFkappaB) signaling, and on the
      transformation of NIH3T3 fibroblasts. Among the six mutations examined, only the
      B-Raf V599E and K600E mutations greatly increased Erk and NFkappaB signaling, and
      the transformation of NIH3T3 cells. The B-Raf F594L mutation moderately elevated
      Erk signaling and NIH3T3 transformation, but did not significantly increase
      NFkappaB signaling. Although the basal kinase activity of the B-Raf T598I mutant
      was comparable with that of wild-type, its oncogenic Ras-induced kinase activity
      was decreased to 60% of wild-type activity. The B-Raf D593V and G595R mutants
      showed severely reduced kinase activity and affected neither NFkappaB signaling
      nor NIH3T3 transforming activity. These results suggest that the B-Raf activation
      segment mutations other than V599E reported in colorectal tumors do not
      necessarily contribute to carcinogenesis by increasing kinase and transforming
      activities.

PMID- 14678967
TI  - Melanoma differentiation associated gene-7, mda-7/interleukin-24, induces
      apoptosis in prostate cancer cells by promoting mitochondrial dysfunction and
      inducing reactive oxygen species.
AB  - Mda-7/IL-24 (Ad.mda-7) is a novel cytokine gene belonging to the interleukin (IL)
      10 gene superfamily. Adenoviral-mediated delivery of mda-7/IL-24 causes growth
      suppression and apoptosis in a wide spectrum of cancer cells, including prostate,
      without harming normal cells. We now demonstrate that Ad.mda-7 selectively
      induces apoptosis in prostate cancer cells by promoting mitochondrial dysfunction
      and reactive oxygen species (ROS) production. Antioxidants (N-acetyl-L-cysteine
      and Tiron) and inhibitors of mitochondrial permeability transition (cyclosporine
      A and bongkrekic acid) inhibit Ad.mda-7-induced mitochondrial dysfunction and
      apoptosis. Conversely, agents augmenting ROS production (arsenic trioxide,
      NSC656240, and PK11195) facilitate Ad.mda-7-induced apoptosis. Ectopic expression
      of Bcl-2 and Bcl-x(L) inhibits mitochondrial changes, ROS production, and
      apoptosis providing additional support for an association between mitochondrial
      dysfunction and Ad.mda-7 action. These studies present definitive evidence that
      changes in mitochondrial function and ROS production are key components
      associated with selective killing of prostate cancer cells by mda-7/IL-24.

PMID- 14678968
TI  - Identification of the interleukin 4 receptor alpha gene as a direct target for
      p73.
AB  - p73 has a high degree of structural homology to p53 and can activate
      transcription of p53-responsive genes. However, analysis of p73-deficient mice
      revealed a marked divergence in the physiological activities of p53 family genes
      and distinguishes p73 from p53. Mice deficient for p73 exhibit profound defects,
      including hippocampal dysgenesis, chronic infection, and inflammation, as well as
      abnormalities in pheromone sensory pathways. p73 plays important roles in
      neurogenesis, sensory pathways, and homeostatic regulation. Here, we found that
      the interleukin 4 receptor alpha (IL-4Ralpha) gene is up-regulated by p73 but not
      significantly by p53 in several human cancer cell lines. IL-4Ralphatranscription
      is also activated in response to cisplatin, a DNA-damaging agent known to induce
      p73. By using small interference RNA designed to target p73, we demonstrated that
      silencing endogenous p73 abrogates the induction of the IL-4Ralpha gene after
      cisplatin treatment. Furthermore, we identified a p73-binding site in the first
      intron of the IL-4Ralpha gene that can directly interact with the p73 protein in
      vivo. This p73-binding site consists of eight copies of a 10-bp consensus p53
      binding motif and is a functional response element that is relatively specific
      for p73 among the p53 family. p73beta promoted localized nucleosomal acetylation
      through recruitment of coactivator p300, indicating that p73 regulates
      transcription of IL-4Ralpha through the unique p73-binding site. We also found
      that p73beta-transfected tumor cells are sensitive to IL-4-mediated apoptosis.
      Our data suggest that IL-4Ralpha could mediate, in part, certain immune responses
      and p73-dependent cell death.

PMID- 14678969
TI  - The CHEK2*1100delC variant acts as a breast cancer risk modifier in non
      BRCA1/BRCA2 multiple-case families.
AB  - The frame-shifting mutation 1100delC in the cell-cycle-checkpoint kinase 2 gene
      (CHEK2) has been reported to be associated with familial breast cancer in
      families in which mutations in BRCA1 and BRCA2 were excluded. To investigate the
      role of this variant as a candidate breast cancer susceptibility allele, we
      determined its prevalence in 237 breast cancer patients and 331 healthy relatives
      derived from 71 non-BRCA1/BRCA2 multiple-case early onset breast cancer families.
      Twenty-seven patients (11.4%) were carrying the CHEK2*1100delC variant. At least
      one carrier was found in 15 of the 71 families (21.1%). There was no evidence of
      cosegregation between the variant and breast cancer, but carrier patients
      developed breast cancer earlier than did noncarriers. We studied CHEK2 protein
      expression in 111, and loss of heterozygosity at CHEK2 in 88 breast tumors from
      these patients. Twelve of 15 tumors from carriers showed absent protein
      expression as opposed to 3 of 76 tumors from noncarriers (P < 0.001). CHEK2 loss
      of heterozygosity was associated with absence of protein expression but not with
      1100delC carrier status. Thus, selecting for breast cancer cases with a strong
      familial background not accounted for by BRCA1 or BRCA2 strongly enriches for
      carriers of CHEK2*1100delC. Our results support a model in which CHEK2*1100delC
      interacts with an as yet unknown gene (or genes) to increase breast cancer risk.

PMID- 14678970
TI  - Mismatch repair-dependent transcriptome changes in human cells treated with the
      methylating agent N-methyl-n'-nitro-N-nitrosoguanidine.
AB  - DNA mismatch repair (MMR) plays a key role in the cytotoxic response of human
      cells to methylating agents, however, the cascade of events leading to cell cycle
      arrest and cell death has yet to be characterized. We studied the role of MMR in
      the transcriptional response to DNA methylation damage in two human cellular
      models: (a). the lymphoblastoid cell line TK6 and its derivative MT1, which is
      mutated in the MMR gene hMSH6; and (b). the epithelial cell line 293T Lalpha in
      which the expression of the MMR gene hMLH1 can be tightly regulated and p53 is
      inactivated. Upon N-methyl-N'-nitro-N-nitrosoguanidine treatment, only cells with
      functional MMR were killed, but the type of cytotoxic response differed. In TK6
      cells, S-phase arrest and apoptosis were accompanied by a dramatic change in gene
      expression, notably, an up-regulation of several genes encoding growth inhibitors
      and proapoptotic factors both p53 dependent and independent. In contrast, the MMR
      dependent transcriptional response in 293T Lalpha cells was substantially less
      pronounced than in TK6 cells, despite an efficient induction of a G(2)-M
      checkpoint and nonapoptotic cell death. Thus, we demonstrate that in human cells
      of different origin, MMR-mediated killing by methylating agents occurs through
      different pathways and regardless of the p53 status. Moreover, once DNA
      methylation damage has been processed by the MMR system, tumor cells might be
      committed to die, although one or more of their signaling pathways are impaired.

PMID- 14678971
TI  - The B subunit of the CCAAT box binding transcription factor complex (CBF/NF-Y) is
      essential for early mouse development and cell proliferation.
AB  - To understand the physiological function of the mammalian heterotrimeric CCAAT
      binding factor CBF, also known as NF-Y, we have generated a conditional Cbf-b
      mouse mutant by introducing loxP sites in the murine Cbf-b/Nf-ya gene. Controlled
      expression of Cre recombinase deletes the gene in vivo, which leads to a loss of
      DNA binding by the CBF complex and hence CBF-mediated transcription. Deletion of
      both Cbf-b alleles causes early embryo lethality, indicating that CBF activity is
      essential for early mouse development. In primary cultures of mouse embryonic
      fibroblasts, conditional inactivation of CBF results in a block in cell
      proliferation and inhibition of S phase or DNA synthesis, which is followed by
      induction of apoptosis. We conclude that the CBF transcription factor complex is
      essential for cell proliferation and viability.

PMID- 14678972
TI  - Comparative analysis of cervical cancer in women and in a human papillomavirus
      transgenic mouse model: identification of minichromosome maintenance protein 7 as
      an informative biomarker for human cervical cancer.
AB  - Human papillomaviruses (HPVs), such as HPV-16, are associated with >99% of
      cervical cancers in women. Two viral oncogenes, E6 and E7, are selectively
      expressed in these cancers. K14E6 and K14E7 transgenic mouse strains, which
      express the HPV16 E6 or E7 gene in stratified squamous epithelia, display many
      acute and long-term phenotypes indicative of the oncogenic potential of E6 and E7
      including epithelial hyperplasia, abrogation of normal DNA damage responses, and
      spontaneous skin tumors. When treated with estrogen, these HPV-16 transgenic mice
      develop a progressive disease leading to cervical cancer that shows many
      histopathological parallels to cervical cancer in women. In this study, we
      evaluated the cervical lesions that arise in these transgenic mice for the
      expression of biomarkers induced in human cervical cancer. These analyses, which
      showed close parallels in the timing and pattern of expression of cyclin E and Ki
      67 in the mouse cervical disease compared with that in humans, provided further
      validation of this HPV-16 transgenic mouse model for human cervical cancer. We
      then used our mouse model to identify minichromosome maintenance protein 7
      (MCM7), an E2F-induced cellular DNA replication factor, as a novel biomarker for
      cervical cancer. In both the mouse and human disease, strong, full thickness
      staining for MCM7 was seen selectively in the epithelium of high-grade
      intraepithelial lesions and in frank cancer. The uniform staining pattern and
      strong signal for MCM7 suggest that MCM7 may be a highly informative biomarker
      for cervical cancer.

PMID- 14678973
TI  - Homologous recombination deficiency leads to profound genetic instability in
      cells derived from Xrcc2-knockout mice.
AB  - DNA damage such as double-strand breaks presents severe difficulties for the cell
      to repair, especially if genetic stability is to be preserved. Recombination of
      the damaged DNA molecule with an undamaged homologous sequence provides a
      potential mechanism for the high-fidelity repair of such damage, and genes
      encoding homologous recombination (HR) proteins have been identified in mammalian
      cells. Xrcc2 is a protein with homology to Rad51, the core component of HR, but
      with a nonredundant role in damage repair. Here, we make the first study of the
      consequences of knocking out one or both copies of the Xrcc2 gene in mouse cells.
      In addition to growth arrest and sensitivity to agents causing severe DNA damage,
      we show that order-of-magnitude higher levels of chromosomal alterations are
      sustained in primary or immortal Xrcc2(-/-) embryonic fibroblasts. Using spectral
      karyotyping, we find that aneuploidy and complex chromosome exchanges, including
      an unexpectedly high frequency of homologue exchanges, are hallmarks of Xrcc2
      deficiency. In addition, we find evidence for mild haploinsufficiency of Xrcc2.
      These responses are linked to several indicators of reduced HR in Xrcc2(-/-)
      cells, including a 30-fold reduction in gene conversion and reduced levels of
      Rad51-focus formation and of sister-chromatid exchange. Our data have
      similarities to recent studies of the disruption of breast cancer-predisposing
      (Brca) genes in mouse cells and are contrasted to analyses of cells carrying
      disruptions of genes in the other main pathway for double-strand break repair,
      nonhomologous end joining.

PMID- 14678974
TI  - Short telomeres and ataxia-telangiectasia mutated deficiency cooperatively
      increase telomere dysfunction and suppress tumorigenesis.
AB  - To examine the role of ataxia-telangiectasia mutated (Atm) in telomere function,
      we generated Atm and telomerase null mice (Atm(-/-) mTR(-/-) iG6 mice). These
      mice exhibited increased germ cell death and chromosome fusions compared with
      either Atm(-/-) or mTR(-/-) iG6 mice. Furthermore, the Atm(-/-) mTR(--) iG6 mice
      had a delayed onset and reduced incidence of thymic lymphoma compared with Atm(-/
      ) mice. The tumors in the Atm(-/-) mTR(-/-) iG6 mice showed increased apoptosis
      and anaphase bridges. Finally, lymphomas from Atm(-/-) mTR(-/-) iG6 mice were
      derived from CD8 immature, single-positive T cells, whereas Atm(-/-) lymphomas
      were from CD4(+)CD8(+) double-positive T cells. We propose that Atm protects
      short telomeres and that Atm deficiency cooperates with short telomeres, leading
      to increased cell death, decreased tumorigenesis, and increased overall survival.

PMID- 14678975
TI  - High-resolution genetic map of X-linked juvenile-type granulosa cell tumor
      susceptibility genes in mouse.
AB  - SWR/Bm (SWR) female mice spontaneously develop early-onset ovarian granulosa cell
      (GC) tumors that can progress to metastatic carcinoma and thus provide a model
      system for human, juvenile-type GC tumors. In SWR mice, GC tumor susceptibility
      is an inherited, polygenic trait that appears at a low frequency. A dramatic
      increase in tumor frequency occurs when the autosomal SWR genetic complement is
      combined with the X-linked Gct4 allele of the mouse strain SJL/Bm (SJL). The
      modifier effect of the SJL Gct4 allele (Gct4(J)) also shows a strong parent-of
      origin effect, occurring only when the Gct4(J) allele is paternally inherited. To
      genetically localize Gct4, we generated seven congenic mouse strains (SWR.SJL-X1
      through -X7) that contained a defined segment of the SJL X chromosome (Chr) on
      the SWR autosomal strain background and mapped Gct4 to a 3 cM region. To better
      define the location of Gct4, we created an additional congenic strain (SWR.CAST
      X) that contains most of the genetically polymorphic Chr X from the strain
      CAST/Ei. From crosses of the SWR.CAST-X and SWR.SJL-X congenic strains, we
      derived males carrying unique combinations of SJL-X and CAST-X segments. Progeny
      testing subsequently revealed a second SJL-derived, GC tumor frequency modifier
      gene, Gct6, located 6.5 cM distal to Gct4 on Chr X. In summary, we have mapped
      two modifier genes on the mouse Chr X that cause high-frequency, juvenile-type GC
      tumor development in female mice. The identity of these genes will provide a
      solid foundation for determination of tumor susceptibility genes in human cases
      of juvenile-type GC tumors.

PMID- 14678976
TI  - Altered serine/arginine-rich protein phosphorylation and exonic enhancer
      dependent splicing in Mammalian cells lacking topoisomerase I.
AB  - DNA topoisomerase I (Topo I) specifically phosphorylates arginine-serine-rich (SR
      proteins) splicing factors and is potentially involved in pre-mRNA-splicing
      regulation. Using a Topo I-deficient murine B lymphoma-derived subclone (P388
      45/C) selected for its resistance to high dosage of the antitumor drug
      camptothecin, we show that Topo I depletion results in the hypophosphorylation of
      SR proteins and impairs exonic splicing enhancer (ESE)-dependent but not
      constitutive splicing. The Affymetrix GeneChip system analysis revealed that
      several alternatively spliced genes, characterized by small exons and large
      introns, are down-regulated in Topo I-deficient cells. Given that ectopic
      expression of green fluorescent protein-Topo I fusion in Topo I-deficient cells
      restores both wild-type phosphorylation of SR proteins and ESE-dependent
      splicing, we conclude that Topo I-mediated phosphorylation plays a specific role
      in ESE-regulated splicing.

PMID- 14678977
TI  - Differential effect of acute and permanent heat shock protein 70 overexpression
      in tumor cells on lysability by cytotoxic T lymphocytes.
AB  - We have shown previously that acute heat shock protein (Hsp) 70 induction in a
      human melanoma cell line containing a doxycycline-inducible Hsp70 expression
      construct increases lysability of these tumor cells by cytotoxic T lymphocyte
      (CTL) without interfering with MHC class I expression and antigen presentation.
      The same parental melanoma cell line has now been transduced retrovirally to
      overexpress Hsp70 permanently. Here we demonstrate that MHC class I cell surface
      expression is again not altered and that these cells, in contrast with acutely
      Hsp70 overexpressing cells, do not show augmentation of CTL-mediated apoptosis.
      Also, long-term induction of Hsp70 in cells with the doxycycline-inducible Hsp70
      construct leads to abrogation of increased lysability. Because, furthermore,
      after heat shock the same permanently Hsp70 overexpressing cells show Hsp70
      induction and increased lysability, it is hypothesized that acutely available
      Hsp70 is able to chaperone proteins that are involved in CTL-mediated apoptosis
      of target cells and to thereby improve their lysability. We also observed that
      permanent but not acute Hsp70 overexpression resulted in decreased levels of
      Hsc70, the constitutively expressed member of the Hsp70 family. Down-regulation
      of Hsc70 occurs at the post-transcriptional level and can be observed also after
      long-term induction of Hsp70 in cells containing the doxycycline-inducible
      expression system. Hsc70 down-regulation might reflect a functional integration
      of the overexpressed Hsp70 on the basis of a chaperone network so that only acute
      induction will provide Hsp70 that can improve tumor cell lysability. The
      implications of the differential effect of acute versus permanent Hsp70
      overexpression for tumor therapy are discussed.

PMID- 14678978
TI  - Expression of matrix metalloproteinases in the microenvironment of spontaneous
      and experimental melanoma metastases reflects the requirements for tumor
      formation.
AB  - Expression of matrix metalloproteinases (MMPs) and their activation in tumor
      cells, as well as tumor surrounding stromal cells have been implicated in tumor
      cell invasion and metastasis. By means of a syngeneic tumor model for either
      experimental or spontaneous metastases, the differential expression of MMPs and
      tissue inhibitors of MMPs (TIMPs) in relation to the microenvironment and the way
      of metastasis induction was characterized. In vitro characterization revealed
      that increased levels of secreted MMP-2, MMP-9, and TIMP-1 were only detectable
      in the most aggressive cell line, B16G3.12BM2. Remarkably, active MMP-2 was
      restricted to this cell line, whereas TIMP-2 and membrane type (MT) 1-MMP
      expression was comparable in all three of the spontaneously metastasizing
      melanoma cell lines investigated. In vivo analysis demonstrated that MMP-2, MMP
      9, and MT1-MMP were predominantly expressed at the tumor-stroma border of s.c.
      tumors. Furthermore, functional active MMP-2 was restricted to this invasive
      front. In spontaneous lymph node or lung metastases, however, MMP-9 was expressed
      both in the center and the periphery of tumors; these areas were largely negative
      for MMP-2 and MT1-MMP. Notably, tumor cells of experimental lung metastases did
      not express MMP-9 at all. These results indicate that expression of MMPs in
      melanoma metastases is not only influenced by their localization but also the
      nature of tumor induction, suggesting that individual MMPs serve specific roles
      during the different stages of metastasis formation.

PMID- 14678979
TI  - The molecular signature of mantle cell lymphoma reveals multiple signals favoring
      cell survival.
AB  - Mantle cell lymphoma (MCL) is a prototypical neoplastic disease in which a common
      cytogenetic alteration, t11;14, leading to cyclin D1 overexpression, is
      associated with other changes that need to be considered in an explanation of the
      clinical, morphological, and molecular variability of this disease. Using a cDNA
      microarray (Oncochip-CNIO) containing clones for 6386 cancer-related genes, we
      have analyzed the expression profiles of a series of 38 cases. After
      normalization with the expression profiling of sorted mantle zone lymphocytes, we
      have related the findings to conventional clinical and molecular variables,
      including immunoglobulin variable heavy chain somatic mutation, blastoid
      cytology, increased proliferation, and long-term survival. MCL signature (446
      genes) includes genes involved in apoptosis, cell cycle, signal transduction, and
      cell structure. Especially striking was the presence of multiple concurrent
      alterations in the tumor necrosis factor and nuclear factor kappaB pathway, and
      the overexpression of IL10R and SPARC genes. We also identified a molecular
      signature for the presence of immunoglobulin variable heavy chain somatic
      mutation, which includes a number of genes potentially relevant in cancer
      (CDC14A, ras, and others). Signatures for proliferation and blastoid cytology
      were also found. An integrated analysis of these data yields a gene-expression
      based survival predictor (26 genes grouped into two clusters), which
      distinguishes half of the patients with a survival probability of 52% at 5 years.
      The predictive model has been confirmed by cross-validation. In conclusion, MCL
      seems to combine a disease-specific signature and different sets of genes of
      which the expression is associated with key clinical, molecular, and
      immunophenotypical events.

PMID- 14678980
TI  - Chemosensitization by a non-apoptogenic heat shock protein 70-binding apoptosis
      inducing factor mutant.
AB  - Heat shock protein 70 (HSP70) inhibits apoptosis and thereby increases the
      survival of cells exposed to a wide range of lethal stimuli. HSP70 has also been
      shown to increase the tumorigenicity of cancer cells in rodent models. The
      protective function of this chaperone involves interaction and neutralization of
      the caspase activator apoptotic protease activation factor-1 and the
      mitochondrial flavoprotein apoptosis-inducing factor (AIF). In this work, we
      determined by deletional mutagenesis that a domain of AIF comprised between amino
      acids 150 and 228 is engaged in a molecular interaction with the substrate
      binding domain of HSP70. Computer calculations favored this conclusion. On the
      basis of this information, we constructed an AIF-derived protein, which is
      cytosolic, noncytotoxic, yet maintains its capacity to interact with HSP70. This
      protein, designated ADD70, sensitized different human cancer cells to apoptosis
      induced by a variety of death stimuli by its capacity to interact with HSP70 and
      therefore to sequester HSP70. Thus, its chemosensitizing effect was lost in cells
      in which inducible HSP70 genes had been deleted. These data delineate a novel
      strategy for the selective neutralization of HSP70.

PMID- 14678981
TI  - Enhanced ubiquitinylation of heat shock protein 90 as a potential mechanism for
      mitotic cell death in cancer cells induced with hypericin.
AB  - A unique property of the photodynamic signal transduction inhibitor hypericin is
      functionality in the dark. We show in tumor cells that hypericin targets the heat
      shock protein (Hsp) 90 chaperone but not Hsp70 (Hsc70) to enhanced
      ubiquitinylation. As a consequence Hsp90 chaperone functionality is abrogated and
      the client proteins, mutant p53, Cdk4, Raf-1, and Plk, are displaced from
      complexes with Hsp90, destabilized, and degraded via a proteasome-independent
      pathway. Decline in Raf-1 prevents downstream activation of extracellular signal
      regulated kinase 1/2 kinases, the Ras/Raf pathway is inhibited, and tumor cell
      proliferation is arrested. The cells exhibit multiple aberrations including
      retardation at G(2)-M, increased cell volume, and multinucleation, all of which
      are hallmarks of mitotic cell death. The studies demonstrate that
      ubiquitinylation of Hsp90 inactivates the chaperone, destabilizes the plethora of
      client proteins, and creates deficiencies in multiple unrelated cellular
      functions. This combination constitutes a mechanism by which hypericin generates
      mitotic cell death in cancer cells.

PMID- 14678982
TI  - Expression profiling and subtype-specific expression of stomach cancer.
AB  - The expression profiling and molecular grouping of stomach cancers has been a
      challenging task because of their complexity and variation. We have analyzed gene
      expression profiles of 22 gastric cancer/nontumor mucosa couples using 14K cDNA
      microarray chips designed for gastric cancer analysis. Upon pairwise analysis of
      the individual couples at the false significance rate 0.91%, 79 and 398 genes
      were reported to be up-regulated and down-regulated in tumors, respectively.
      Tumors were clustered into two groups having high and low inflammatory
      infiltration, respectively. The latter consisted of three subgroups, including
      diffuse type carcinomas and intestinal types with distinct pathological
      characteristics of aggressive behavior. When the pooled tumor was hybridized
      against the pooled nontumor mucosa samples, more genes were detected to express
      differentially than those detected by the pairwise analysis at the same threshold
      level. However, they did not render satisfactory clustering of individual tumors.
      Our data showed that stomach cancers could be clustered effectively using stomach
      specific microarrays and pairwise analysis of tumor/nontumor mucosa couples. It
      is suggested that the application of specific goal-oriented experimental
      designing would be advantageous for efficient analysis of expression profiles of
      such a complex disease as gastric cancer.

PMID- 14678983
TI  - Inducible prostate intraepithelial neoplasia with reversible hyperplasia in
      conditional FGFR1-expressing mice.
AB  - Accurate determination of the contributions of oncogenes toward tumor progression
      requires their regulation. Herein, we created transgenic mice with prostate
      specific expression of ligand-inducible FGFR1 or FGFR2, based on lipid-permeable
      dimerizing molecules, called chemical inducers of dimerization. Despite extensive
      homology and equivalent expression by both chimeric receptors in the ventral
      prostate gland, only FGFR1 triggers detectable nuclear translocation of Erk and
      progression to prostatic intraepithelial neoplasia (PIN). Induction of PIN grade
      I-II, indicated by multiple layers of atypical cells, is seen consistently by 12
      weeks of chemical inducers of dimerization treatment. By 6 months, more extensive
      nuclear atypia, thickened "reactive" stroma, and basement membrane herniation
      occurs, corresponding to PIN IV. By timed removal of FGFR1 signaling, we show
      that induced hyperplasia is reversible until extensive intraductal
      vascularization occurs, but continued progression requires prolonged FGFR1
      signaling. Additionally, by highlighting differences between the two receptors
      and creating the foundation for controlling FGFR1 signaling during prostate
      cancer progression, a model of early stage prostate cancer is established for
      developing targeted intervention directed toward the FGFR signaling axis.

PMID- 14678984
TI  - Sensitive noninvasive monitoring of tumor perfusion during antiangiogenic therapy
      by intermittent bolus-contrast power Doppler sonography.
AB  - Intermittent bolus-contrast power Doppler ultrasound was used for noninvasive,
      quantitative monitoring of tumor perfusion during antiangiogenic therapy.
      Subcutaneous heterotransplants of human squamous cell carcinoma cells in nude
      mice were treated with a blocking antibody to vascular endothelial growth factor
      receptor 2 (DC101) and repeatedly examined at weekly intervals. Using
      replenishment kinetics of microbubbles (Levovist) tumor vascularization,
      including capillary blood flow, was clearly visualized by this dynamic ultrasound
      method allowing the determination of a comprehensive functional status of tumor
      vascularization (blood volume, blood flow, perfusion, and mean blood velocity) in
      all examined tumors. DC101 treatment decreased tumor blood flow (-64%) and volume
      (-73%) compared with untreated controls (+409% and +185%, respectively).
      Regression of functional vessel parameters was observed early well before
      reduction of tumor size. The treatment-related amount of reduction in tumor
      volume was directly correlated for the initial tumor blood flow before start of
      therapy and the perfusion calculated at the preceding examination. The vessel
      density (immunofluorescence staining with CD31 antibody at different time points)
      showed an excellent correlation with the calculated relative blood volume (k =
      0.84, P < 0.01), thereby validating intermittent sonography as a useful
      monitoring method. We conclude that intermittent sonography is a promising tool
      for comprehensive monitoring of antiangiogenic or proangiogenic therapies,
      especially during early stages of treatment, thus yielding information regarding
      a prospective evaluation of therapy effects beyond the follow up of tumor size.

PMID- 14678985
TI  - HIPK2 regulates transforming growth factor-beta-induced c-Jun NH(2)-terminal
      kinase activation and apoptosis in human hepatoma cells.
AB  - Homeodomain-interacting protein kinase 2 (HIPK2) is a serine/threonine kinase
      involved in transcriptional regulation and apoptosis. Here we demonstrate that
      HIPK2 regulates transforming growth factor (TGF) beta-induced c-Jun NH(2)
      terminal kinase (JNK) activation and apoptosis. HIPK2 colocalizes with Daxx, a
      protein acting in TGF-beta-induced JNK activation and apoptosis, in promyelocytic
      leukemia (PML) nuclear bodies, and triggers PML-nuclear body disruption and
      release of Daxx. HIPK2 interacts in vitro and in vivo via its kinase domain with
      Daxx, and a fraction of Daxx coprecipitates with HIPK2 under physiological
      conditions. Moreover, overexpression of HIPK2 leads to Daxx phosphorylation, and
      ectopic expression of HIPK2 activates the JNK signaling pathway, which is
      enhanced by coexpression of Daxx. HIPK2 signals to JNK via a pathway using Daxx
      and the mitogen-activated protein kinase kinases MKK4/SEK1 and MKK7. Ectopic
      expression of HIPK2 and Daxx potentiates TGF-beta-induced apoptosis in human p53
      deficient hepatocellular carcinoma cells. Finally, we demonstrate that knockdown
      of endogenous HIPK2 using RNA interference inhibits TGF-beta-induced JNK
      activation and apoptosis. Taken together, our findings indicate that HIPK2
      participates in the TGF-beta signaling pathway leading to JNK activation and
      apoptosis.

PMID- 14678986
TI  - Monoclonal antibodies with defined recognition sequences in the stem region of
      CD44: detection of differential glycosylation of CD44 between tumor and stromal
      cells in tissue.
AB  - CD44 is an enigmatic cell adhesion molecule acting as a major receptor for
      hyaluronan and playing roles in many biological and pathological processes such
      as lymphocyte homing, T-cell activation, wound healing, angiogenesis, and
      metastatic spread of tumor cells. However, the complexity of the molecule, with
      its alternatively spliced variants, extensive glycosylation, and processing by
      different proteases, has hampered detailed analysis. In this study, we prepared
      four monoclonal antibodies (285-2F12, 284-43F1, 268-1F5, and 294-6F2) and one
      polyclonal antibody (C6) that recognize defined sequences in the stem region of
      CD44H. Interestingly, two of the monoclonal antibodies, 268-1F5 and 294-6F2,
      failed to recognize the CD44 expressed in five of the seven human tumor cell
      lines examined by Western blotting. Treatment of the samples with a combination
      of neuraminidase and O-glycosidase as well as the expression of mutants with site
      directed mutations at possible modification sites rendered the CD44 reactive to
      the antibodies. Thus, the reactivity of the antibodies is sensitive to O
      glycosylation presumably near the recognition sites. Glycosylation of CD44 that
      affects reactivity to the antibodies was found to be regulated differentially
      between tumor and stromal cells in two breast and three oral carcinoma tissues.
      Antibody 268-1F5 reacted to the tumor cells, but not to the cells in the
      surrounding stroma. On the other hand, the reactivity of 294-6F2 to the cells was
      opposite between the two tumor types. Thus, these sets of antibodies are useful
      to detect and analyze the as-yet-unknown roles of site-specific glycosylation of
      CD44, particularly in tumors.

PMID- 14678987
TI  - Reduction in Smad2/3 signaling enhances tumorigenesis but suppresses metastasis
      of breast cancer cell lines.
AB  - The role of transforming growth factor beta in breast cancer is controversial
      with tumor suppressor and pro-oncogenic activities having been demonstrated. To
      address whether the same or different signal transduction pathways mediate these
      opposing activities, we manipulated the Smad2/3 signaling pathway in cells of
      common origin but differing degrees of malignancy derived from MCF10A human
      breast cells. We show that interference with endogenous Smad2/3 signaling
      enhances the malignancy of xenografted tumors of premalignant and well
      differentiated tumor cells but strongly suppresses lung metastases of more
      aggressive carcinoma cells after tail vein injection. Overexpression of Smad3 in
      the same cells has opposite effects. The data demonstrate that the Smad2/3
      signaling pathway mediates tumor suppressor and prometastatic signals, depending
      on the cellular context.

PMID- 14678988
TI  - Activation of nuclear factor-kappaB p50 homodimer/Bcl-3 complexes in
      nasopharyngeal carcinoma.
AB  - EBV latent infection is associated with the development of lymphoid and
      epithelial malignancies such as nasopharyngeal carcinoma (NPC). The EBV latent
      membrane protein 1 (LMP1) acts as a constitutively active tumor necrosis factor
      receptor and activates cellular signaling pathways such as c-Jun-NH(2)-terminal
      kinase, cdc42, Akt, and nuclear factor (NF)-kappaB. In epithelial cells, two
      regions of LMP1 induce specific forms of NF-kappaB. COOH-terminal activating
      region 2 only activates p52/p65 dimers, whereas COOH-terminal activating region 1
      activates p50/p50, p50/p52, and p52/p65 dimers and also uniquely up-regulates the
      epidermal growth factor receptor (EGFR) at the mRNA level. Deregulation of
      specific NF-kappaB members is associated with the development of many cancers. In
      this study, the status of NF-kappaB activation was investigated in NPC to
      determine which NF-kappaB dimers may contribute to the development of NPC.
      Electrophoretic mobility shift assay, immunoblot, ELISA, and immunohistochemistry
      data demonstrate that in NPC, NF-kappaB p50 homodimers are specifically
      activated, and this activation is not dependent on LMP1 expression.
      Coimmunoprecipitation assays indicate that homodimers are bound to the
      transcriptional coactivator Bcl-3, and chromatin immunoprecipitation indicates
      that this complex is bound to NF-kappaB consensus motifs within the egfr promoter
      in NPC. The discrete yet striking NF-kappaB p50 activation in NPC suggests that
      p50/p50 homodimers may be important factors in the development of NPC and may
      contribute to oncogenesis through transcriptional up-regulation of target genes
      through their interaction with Bcl-3.

PMID- 14678989
TI  - CD29 and CD7 mediate galectin-3-induced type II T-cell apoptosis.
AB  - Galectin (Gal)-3, a M(r) 31000 member of the beta-galactoside-binding protein
      family, is a multifunctional protein implicated in a variety of biological
      functions, including tumor cell adhesion, proliferation, differentiation,
      angiogenesis, apoptosis, cancer progression, and metastasis. Here, we report that
      secreted extracellular Gal-3 can signal apoptosis of human T leukemia cell lines,
      human peripheral blood mononuclear cells, and activated mouse T cells after
      binding to cell surface glycoconjugate receptors through carbohydrate-dependent
      interactions because the apoptotic effect was found to be inhibited by lactose,
      specific sugar inhibitor, and to be dose dependent. However, the apoptosis
      sensitivity to Gal-3 varied among the different cell lines tested. We report that
      Gal-3-null Jurkat, CEM, and MOLT-4 cells were significantly more sensitive to
      exogenous Gal-3 than SKW6.4 and H9 cells, which express Gal-3, suggesting a cross
      talk between the antiapoptotic activity of intracellular Gal-3 and proapoptotic
      activity of extracellular Gal-3. Furthermore, Gal-3-transfected CEM cells were
      found to be more resistant to C(2)-ceramide-induced apoptosis than the control
      CEM cells. Identification of Gal-3 cell surface receptors revealed that Gal-3
      binding to CD7 and CD29 (beta(1) integrin) induced apoptosis. Gal-3 binding to
      its cell surface receptors results in activation of mitochondrial apoptosis
      events including cytochrome c release and caspase-3 activation, but not caspase-8
      activation. Taken together, these results suggest that the induction of T-cell
      apoptosis by secreted Gal-3 may play a role in the immune escape mechanism during
      tumor progression through the induction of apoptosis to cancer-infiltrating T
      cells. The induction of T-cell apoptosis by secreted Gal-3 is dependent in part
      on the presence or absence of cytoplasmic Gal-3, providing a new insight for the
      immune escape mechanism of cancer cells.

PMID- 14678990
TI  - Integrin alpha1beta1 and alpha2beta1 are the key regulators of hepatocarcinoma
      cell invasion across the fibrotic matrix microenvironment.
AB  - As with many types of cancer, cell motility is an important factor in the
      progression and metastasis of hepatocellular carcinomas (HCC). HCC is associated
      with significant fibrosis in the liver. The fibrotic microenvironment in the
      liver is characterized by an altered composition of the extracellular matrix
      (ECM) and an abundance of growth factors that are likely conducive to migration
      of HCC cells. The purpose of this study was to delineate promigratory stimuli
      within the fibrotic microenvironment and to identify specific targets for
      prevention of HCC cell migration. We used a modified Boyden chamber system that
      allowed distinction between chemotactic (indirect stimulation) and haptotactic
      (direct stimulation) migration of two distinct HCC cell lines across the ECM
      coated membrane. Fibrotic microenvironment-associated growth factors, such as
      transforming growth factor beta1 (TGF-beta1), basic fibroblast growth factor
      (bFGF), and epidermal growth factor (EGF), induced chemotactic and haptotactic
      migration of HepG2 and Chang cells. Neutralizing antibodies to individual growth
      factors significantly decreased chemotactic and haptotactic migration.
      Haptotactic stimulation, but not chemotactic stimulation of HCC cell lines with
      TGF-beta1, bFGF, and EGF, induced production of matrix metalloproteinase (MMP) 2,
      a potential mediator of migration. Inhibition of MMPs significantly decreased
      haptotactic migration induced by individual growth factors but had an
      insignificant effect on chemotactic migration, suggesting an MMP-independent
      migration in this setting. Inhibition of cell-ECM interactions with blocking
      antibodies to alpha1 and alpha2 integrins were sufficient to inhibit both
      haptotactic and chemotactic migration induced by individual growth factors,
      strongly suggesting that targeting these integrins to abrogate pathogenic cell
      ECM interactions might be a promising tool for inhibiting growth factor-induced
      invasion and metastasis of HCC.

PMID- 14678991
TI  - Corin-mediated processing of pro-atrial natriuretic peptide in human small cell
      lung cancer cells.
AB  - Corin is a recently discovered pro-atrial natriuretic peptide (ANP) convertase
      that is abundantly expressed in the heart. ANP is a cardiac hormone but can be
      secreted ectopically by certain cancers including small cell lung cancer (SCLC).
      In this study, we examined the role of corin in ANP production by SCLC cells.
      Reverse transcription-PCR detected corin mRNA expression in all nine SCLC cell
      lines examined and ANP mRNA expression in seven of the nine cell lines. In
      contrast, arginine vasopressin mRNA was detected in only five of the nine SCLC
      cell lines studied. Corin-expressing SCLC cells were capable of converting
      recombinant human pro-ANP to biologically active ANP, as determined by Western
      analysis and a cyclic GMP assay. Transfection of small interfering RNA duplexes
      directed against the corin gene completely blocked the processing of pro-ANP in
      the SCLC cells. Our results show that corin functions as a pro-ANP convertase in
      SCLC cells. We also suggest that the expression of corin may contribute to the
      pathogenesis of the syndrome of inappropriate secretion of antidiuretic hormone
      associated with certain cancers.

PMID- 14678992
TI  - Notch1 signaling inhibits growth of human hepatocellular carcinoma through
      induction of cell cycle arrest and apoptosis.
AB  - Notch signaling plays a critical role in maintaining the balance between cell
      proliferation, differentiation, and apoptosis; hence, perturbed Notch signaling
      may contribute to tumorigenesis. Hepatocellular carcinoma (HCC) is one of the
      most common malignant tumors in Africa and Asia. The mechanisms that orchestrate
      the multiple oncogenic insults required for initiation and progression of HCC are
      not clear. We constitutively overexpressed active Notch1 in human HCC to explore
      the effects of Notch1 signaling on HCC cell growth and to investigate the
      underlying molecular mechanisms. We show here that overexpression of Notch1 was
      able to inhibit the growth of HCC cells in vitro and in vivo. Biochemical
      analysis revealed the involvement of cell cycle regulated proteins in Notch1
      mediated G(0)/G(1) arrest of HCC cells. Compared with green fluorescent protein
      (GFP) control, transient transfection of Notch1 ICN decreased expression of
      cyclin A (3.5-fold), cyclin D1 (2-fold), cyclin E (4.5-fold), CDK2 (2.8-fold),
      and the phosphorylated form of retinoblastoma protein (3-fold). Up-regulation of
      p21(waf/cip1) protein expression was observed in SMMC7721-ICN cells stably
      expressing active Notch1 but not in SMMC7721-GFP cells, which only express GFP.
      Furthermore, a 12-fold increase in p53 expression and an increase (4.8-fold) in
      Jun-NH(2)-terminal kinase activation were induced in SMMC7721-ICN cells compared
      with SMMC7721-GFP cells. In contrast, expression of the antiapoptotic Bcl-2
      protein could not be detected in SMMC7721-ICN cells. These findings suggest that
      Notch1 signaling may participate in the development of HCC cells, affecting
      multiple pathways that control both cell proliferation and apoptosis.

PMID- 14678993
TI  - Mitogen-activated protein kinase pathway-dependent tumor-specific survival
      signaling in melanoma cells through inactivation of the proapoptotic protein bad.
AB  - Mitogen-activated protein kinase (MAPK) signaling regulates fundamental cellular
      functions including proliferation, differentiation, and survival. We have
      demonstrated previously that inhibiting MAPK signaling induces apoptosis in
      melanoma cells but not in normal melanocytes, suggesting that the MAPK pathway
      propagates essential survival signals in melanoma cells. Here, we report that the
      90-kDa ribosomal S6 kinase (RSK), a downstream effector in the MAPK signaling
      cascade, phosphorylates and inactivates the Bcl-2 homology 3-only proapoptotic
      protein Bad, thereby mediating a MAPK-dependent tumor-specific survival signal in
      melanoma cells. The MAPK kinase (MEK)/extracellular signal-regulated kinase
      (ERK)/RSK MAPK signaling module is constitutively hyperactivated, and Bad is
      maintained in its inactive state by phosphorylation at Ser(75) in a MEK/ERK/RSK
      dependent manner in melanoma cells. In contrast, in normal melanocytes, Bad is
      highly phosphorylated at multiple residues (Ser(75), Ser(99), and Ser(118)) in a
      MAPK pathway-independent manner. Importantly, ectopic expression of a
      constitutively activated RSK mutant abrogates Bad activation and renders melanoma
      cells resistant to apoptosis induced by a MEK inhibitor. Furthermore,
      overexpressing alanine-substituted (S75A) Bad further sensitizes melanoma cells
      to MEK inhibitor-induced apoptosis. Our results suggest that the MAPK pathway
      mediates melanoma-specific survival signaling by differentially regulating RSK
      mediated phosphorylation of the proapoptotic protein Bad and may present
      potentially selective therapeutic targets for the treatment of melanomas.

PMID- 14678995
TI  - Endostatin inhibits the vascular endothelial growth factor-induced mobilization
      of endothelial progenitor cells.
AB  - Circulating endothelial cells (CECs) are present in peripheral blood and have
      been shown to contribute to normal and pathological neovascularization.
      Antiangiogenic molecules can inhibit neovascularization in tumors and other
      sites, but their effect on CECs has not yet been determined. We hypothesize that
      angiogenic factors will increase the number of CECs, and conversely,
      antiangiogenic treatment will reduce these numbers. Mice treated with high levels
      of vascular endothelial growth factor (VEGF) showed increased numbers of Flk-1
      positive cells in peripheral blood and endothelial cell colonies compared with
      vehicle-treated controls. These changes were accompanied by increased bone marrow
      neovascularization. In contrast, mice that received VEGF and endostatin had
      significantly lower numbers of CECs and reduced bone marrow vascularization.
      Endostatin-induced apoptosis was probably responsible for the decreased number of
      CECs. Systemic delivery of a VEGF antagonist, soluble Flt-1, also inhibited the
      VEGF-induced increase in CECs. These results were further confirmed in a
      Tie2/LacZ mouse model, in which endostatin reduced the number of beta
      galactosidase-expressing peripheral blood mononuclear cells. We propose that
      endothelial progenitor cells are a novel target for endostatin and suggest that
      the relative numbers of CECs can serve as a surrogate marker for the biological
      activity of antiangiogenic treatment.

PMID- 14678994
TI  - EWS/ETS fusions activate telomerase in Ewing's tumors.
AB  - EWS/ETS is a chimeric protein identified in most Ewing's sarcomas. Although
      EWS/ETS has been shown to activate transcription as a transcription factor, the
      detailed targets of EWS/ETS in transformed cells have not been clarified. Herein,
      we demonstrate that telomerase is a new target of EWS/ETS fusions. Both
      telomerase activity and the expression level of telomerase reverse transcriptase
      (TERT) mRNA were up-regulated in NIH3T3 cells transformed by EWS/E1AF and
      EWS/FLI1 as well as in two Ewing's sarcoma cell lines. Luciferase assay using the
      TERT promoter revealed that EWS/E1AF and EWS/FLI1 function as positive regulators
      of TERT transcription in an ETS binding site-independent manner. EWS/ETS appeared
      to be included in the initiation complex of TERT transcription and to cooperate
      with CREB-binding protein (CBP)/p300. When EWS/FLI1 was knocked down in Ewing's
      sarcomas cells by RNA interference, the expression level of TERT mRNA and the
      telomerase activity were significantly decreased. These findings indicate that
      EWS/ETS fusion proteins activate human telomerase activity in Ewing's tumors
      through up-regulation of TERT gene expression, probably as a transcriptional
      coactivator.

PMID- 14678996
TI  - Cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs inhibit
      hepatocyte growth factor/scatter factor-induced angiogenesis.
AB  - Epidemiological studies have indicated a reduced risk of malignancies with the
      use of nonsteroidal anti-inflammatory drugs (NSAIDs), although the exact
      mechanisms are debated. NSAIDs inhibit angiogenesis, which is a key step for
      tumor growth. Hepatocyte growth factor/scatter factor (HGF/SF), a potent and
      independent angiogenic factor, has been implicated in tumorigenesis, but limited
      knowledge exists on the potential targets for inhibiting HGF/SF-induced
      pathological angiogenesis. The current study was designed to elucidate the
      possible role of cyclooxygenase (COX) downstream of HGF/SF during angiogenesis
      and to evaluate the potential for harnessing NSAIDs as a therapeutic strategy.
      Known NSAIDs were classified as COX-1 or COX-2 selective based on their activity
      in a platelet aggregation experiment. The inhibitors were administered into a
      polyether polyurethane scaffold implant in mice at the selected doses, and the
      total neovascularization after the administration of HGF/SF was quantified using
      a (133)Xenon clearance technique, vessel counts, and immunohistochemistry.
      Angiogenesis was also quantized into chemoinvasion, migration, proliferation, and
      tube formation events in vitro, and the effects of the NSAIDs were evaluated on
      HGF/SF-induced activity of human umbilical vein endothelial cells (HUVECs).
      HGF/SF accelerated the angiogenic process in the murine implant, and this
      activity was inhibited by COX-2-selective meloxicam and NS398. The COX-1
      inhibitors ketoprofen and SC560 failed to inhibit the HGF/SF-induced angiogenic
      events in vitro and in vivo. A COX-2 blockade inhibited the HGF/SF-induced
      chemoinvasion and migration of human umbilical vein endothelial cells, without
      affecting the proliferative or tubulogenic responses. Western blots revealed the
      induction COX-2 expression after HGF/SF treatment, and the pharmacological
      inhibition of COX-2 executed a temporal inhibition of phosphorylation of the
      mitogen-activated protein kinases. The current study, for the first time,
      implicates COX-2 as a downstream signal during HGF/SF-induced angiogenesis,
      temporally impinging on the mitogen-activated protein kinase signaling. However,
      the mediation is restricted to only the early events of the angiogenic process,
      emphasizing the chemopreventive role for NSAIDs. Few therapeutic options
      currently exist for HGF/SF-induced pathological angiogenesis, and the vast
      knowledge on COX-2 inhibitors can be harnessed to design a newer therapeutic
      approach.

PMID- 14678997
TI  - A chemokine receptor antagonist inhibits experimental breast tumor growth.
AB  - The leukocyte infiltrate of human and murine epithelial cancers is regulated by
      chemokine production in the tumor microenvironment. In this article, we tested
      the hypothesis that chemokine receptor antagonists may have anticancer activity
      by inhibiting this infiltrate. We first characterized CC chemokines, chemokine
      receptors, and the leukocyte infiltrate in the 410.4 murine model of breast
      cancer. We found that CCL5 (RANTES) was produced by the tumor cells, and its
      receptors, CCR1 and CCR5, were expressed by the leukocyte infiltrate. As Met-CCL5
      is an antagonist of CCR1 and CCR5 with activity in models of inflammatory
      disease, we tested its activity against 410.4 tumors. After 5 weeks of daily
      treatment with Met-CCL5, the volume and weight of 410.4 tumors was significantly
      decreased compared with control-treated tumors. Met-CCL5 was also active against
      established tumors. The total cell number obtained after collagenase digestion
      was decreased in Met-CCL5-treated tumors as was the proportion of infiltrating
      macrophages. Furthermore, chemokine antagonist treatment increased stromal
      development and necrosis. Our results provide direct evidence that macrophages
      contribute to tumor development and are the first indication that chemokine
      receptor antagonists may provide novel strategies in cancer prevention and
      treatment.

PMID- 14678998
TI  - The oncolytic effect of recombinant vesicular stomatitis virus is enhanced by
      expression of the fusion cytosine deaminase/uracil phosphoribosyltransferase
      suicide gene.
AB  - Vesicular stomatitis virus (VSV) has recently been demonstrated to exhibit
      significant oncolytic capabilities against a wide variety of tumor models in
      vitro and in vivo. To potentially enhance the oncolytic effect, we generated a
      novel recombinant VSV (rVSV) that expressed the fusion suicide gene Escherichia
      coli cytosine deaminase (CD)/uracil phosphoribosyltransferase (UPRT). rVSV
      encoding the CD/UPRT fusion gene (VSV-C:U) exhibited normal growth properties and
      generated high levels of biologically active CD/UPRT that could catalyze the
      modification of 5-fluorocytosine into chemotherapeutic 5-fluorouracil (5-FU),
      which exhibited considerable bystander effect. Intratumoral inoculation of VSV
      C:U in the presence of the systemically administered prodrug 5-fluorocytosine
      produced statistically significant reductions in the malignant growth of
      syngeneic lymphoma (A20) or mammary carcinoma (TSA) in BALB/c mice compared with
      rVSV treatments or with control 5-FU alone. Aside from detecting prolonged
      therapeutic levels of 5-FU in VSV-C:U-treated animals harboring TSA tumors and
      enhancing bystander killing of tumor cells, we demonstrated marked activation of
      IFN-gamma-secreting cytotoxic T cells by enzyme-linked immunospot analysis that
      may have also facilitated tumor killing. In conclusion, the insertion of the
      fusion CD/UPRT suicide gene potentiates the oncolytic efficiency of VSV by
      generating a strong bystander effect and by contributing to the activation of the
      immune system against the tumor without detrimentally altering the kinetics of
      virus-mediated oncolysis and may be useful in the treatment of malignant disease.

PMID- 14678999
TI  - In vivo efficacy of recombinant methioninase is enhanced by the combination of
      polyethylene glycol conjugation and pyridoxal 5'-phosphate supplementation.
AB  - Recombinant methioninase (rMETase) is an enzyme active in preclinical mouse
      models of human cancer. The efficacy of rMETase is due to depletion of plasma
      methionine, an amino acid for which tumors generally have an abnormally high
      methionine requirement. Furthermore, transient methionine depletion results in a
      markedly increased sensitivity of the tumors to several chemotherapeutic agents.
      This study characterized methods to prolong the half-life of rMETase to extend
      the in vivo period of depletion of plasma and tumor methionine. In the present
      study, rMETase was coupled to methoxypolyethylene glycol succinimidyl glutarate
      5000 in order to prolong the half-life of rMETase and thus extend the in vivo
      period of depletion of plasma and tumor methionine. Matrix-assisted laser
      desorption ionization mass spectrometry indicated that one sub-unit of rMETase
      was modified by approximately 4, 6 and 8 PEG molecules when rMETase was PEGylated
      at molar ratios of PEG/rMETase of 30/1, 60/1, and 120/1, respectively. PEG
      rMETase (120/1) had a serum half-life increase of 20-fold, and methionine
      depletion time increased 12-fold compared to unmodified rMETase. The increase in
      in vivo half-life depended on the extent of PEGylation of rMETase. In addition, a
      remarkable prolongation of in vivo activity and effective methionine depletion by
      the PEG-rMETase was achieved by the simultaneous administration of pyridoxal 5'
      phosphate. PEGylation also reduced the immunogenicity of rMETase. The extent of
      reduction in immunogenicity depended on the number of residues PEGylated. PEG
      rMETase 30/1 had a 10-fold decrease in IgG titer while PEG-rMETase 120/1 had a
      10(4)-fold decreased titer compared to naked rMETase. Thus, the molecular
      modification of PEGylation confers critical new properties to rMETase for
      development as a cancer therapeutic.

PMID- 14679000
TI  - Complete regression of experimental solid tumors by combination LEC/chTNT-3
      immunotherapy and CD25(+) T-cell depletion.
AB  - LEC/chTNT-3, a chemokine fusion protein generated previously in our laboratory,
      produces a 40-60% reduction in well-established solid tumors of the BALB/c mouse.
      In this study, CD25(+) T-cell depletion was used in combination with LEC/chTNT-3
      treatment to enhance the therapeutic value of this approach. In two tumor models
      (Colon 26 and RENCA), this combination immunotherapy produced complete regression
      of established s.c. tumors after 5 consecutive days of i.v. treatment. To show
      that targeted LEC is critical to these results, similar combination studies were
      performed with chTNT-3/cytokine fusion proteins consisting of human interleukin
      2, murine IFN-gamma, and murine granulocyte macrophage colony-stimulating factor
      using identical treatment regimens. These studies showed no significant
      improvement indicating that combination therapy with anti-CD25(+) antisera
      requires LEC localization to tumor to produce complete regression. To study the
      mechanism of this remarkable response, immunotherapeutic studies were repeated in
      knockout mice and showed that successful treatment with CD25(+) depletion was
      dependent on the presence of IFN-gamma but not perforin. Other studies using real
      time PCR, ex vivo proliferation, and intracellular cytokine staining with
      lymphocytes from tumor draining lymph nodes, suggested that this combination
      treatment was associated with increased T-helper 1 cytokine expression, enhanced
      T-cell activation, and increased IFN-gamma production by T cells. Rechallenge
      experiments showed that combination LEC/chTNT-3 treatment and CD25(+) depletion
      produced long-acting memory cells capable of preventing re-engraftment of the
      same but not different tumor cell lines. These studies suggest that
      LEC/monoclonal antibody fusion proteins, when used in combination with CD25(+) T
      cell depletion, is a viable method of immunotherapy for the treatment of solid
      tumors.

PMID- 14679001
TI  - Combination treatment with 17-N-allylamino-17-demethoxy geldanamycin and acute
      irradiation produces supra-additive growth suppression in human prostate
      carcinoma spheroids.
AB  - Failure to control localized prostate cancer can result not only in localized
      disease progression but also distant metastatic spread. Whereas significant
      advances in both surgical technique and radiation therapy have improved local
      control rates with decreased morbidity, consistent long-term control remains
      elusive. This study investigates the potential of 17-N-allylamino-17-demethoxy
      geldanamycin (17AAG), a geldanamycin derivative, to sensitize tumor cells to
      ionizing radiation, permitting a significant improvement to targeted
      radiotherapies of prostate carcinoma. As a monotherapeutic, 17AAG functions to
      modulate the action of heat shock protein 90, ultimately affecting a multitude of
      cellular signaling pathways. It is in Phase I trial and has shown promise in
      controlling prostate cancer progression. Human prostate tumor cells (LNCaP and
      CWR22Rv1) were grown as spheroids and incubated for 96 h with increasing doses of
      17AAG immediately before and after 2 or 6 Gy low linear energy transfer (LET),
      high dose-rate irradiation (Cs-137 irradiator). Twelve or 24 spheroids (initial
      diameter, 150-200 microm) were used per experiment. Response was determined by
      spheroid volume measurements taken over at least 40 days, after treatment.
      Incubation of either cell line with 17AAG (<or=1000 nM) or irradiation (<or=6 Gy)
      alone resulted in transient median growth delays ranging from 2 to 9 days
      (relative to controls). Combining treatments produced dose- and cell line
      dependent supra-additive responses. For LNCaP spheroids, the combination of 2 Gy
      and 100 nM 17AAG resulted in growth delays additive of the treatments
      individually; however, increasing either the radiation to 6 Gy or the 17AAG
      concentration to 1000 nM led to synergistic interactions. Similarly, synergy was
      noted in CWR22Rv1 studies at only 6 Gy and 1000 nM 17AAG. Terminal
      deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and Ki67 staining
      of spheroid sections revealed the increased growth control to be a function of
      spheroids failing to re-enter the cell cycle. For all 6 Gy experiments, cells
      remaining from each of the spheroids that failed to regrow were transferred to
      adherent dishes to evaluate clonogenicity; growth-controlled spheroids also
      failed to form colonies within 2 weeks of being plated. These results suggest
      that significant gains in treatment effectiveness may be obtained by combining
      these treatment modalities, warranting additional preclinical investigation.

PMID- 14679002
TI  - Characterization of ARC-111 as a novel topoisomerase I-targeting anticancer drug.
AB  - 8,9-Dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxy-5H
      dibenzo[c,h][1,6] naphthyridin-6-one (ARC-111, topovale) is a new synthetic
      antitumor agent. In the current study, we show that ARC-111 is highly potent in
      scid mice carrying human tumor xenografts. ARC-111 was shown to be as active as
      camptothecin (CPT)-11 in the HCT-8 colon tumor model, and compared favorably with
      CPT-11 and topotecan in the SKNEP anaplastic Wilms' tumor model. In tissue
      culture models, ARC-111 exhibited low nM cytotoxicity against a panel of cancer
      cells. ARC-111 cytotoxicity as well as ARC-111-induced apoptosis was reduced >100
      fold in CPT-resistant topoisomerase I (TOP1)-deficient P388/CPT45 cells as
      compared with P388 cells. Similarly, ARC-111 cytotoxicity was greatly reduced in
      CPT-resistant CPT-K5 and U937/CR cells, which express CPT-resistant mutant TOP1,
      suggesting that the cytotoxic target of ARC-111 is TOP1. Indeed, ARC-111, like
      CPT, was shown to induce reversible TOP1 cleavage complexes in tumor cells as
      evidenced by specific reduction of the TOP1 immunoreactive band in a band
      depletion assay, as well as elevation of small ubiquitin modifier-TOP1 conjugate
      levels and activation of 26S proteasome-mediated degradation of TOP1. Unlike CPT,
      ARC-111 is not a substrate for the ATP-binding cassette transporter breast cancer
      resistance protein. In addition, ARC-111 cytotoxicity was not significantly
      reduced in the presence of human serum albumin. These results suggest that ARC
      111 is a promising new TOP1-targeting antitumor drug with a different drug
      resistance profile than CPT.

PMID- 14679003
TI  - Synergistic effect of metronomic dosing of cyclophosphamide combined with
      specific antitumor immunotherapy in a murine melanoma model.
AB  - Immunotherapy could be combined with conventional chemotherapeutic modalities
      aimed at reducing tumor burden. Such combination therapy may be most useful when
      "metronomic" doses of antineoplastic drugs are used, thereby potentially avoiding
      some of the immunosuppressive effects of these drugs. Recent studies have shown
      that some conventional antineoplastic drugs can be exploited for antiangiogenic
      capacities, a strategy that requires drugs to be administered at regular
      intervals. We therefore investigated whether such metronomic therapy with the
      alkylating agent cyclophosphamide (CTX) could be effectively combined with
      immunotherapy eliciting tumor-reactive CTLs. An immunization protocol using
      injection of recombinant DNA followed by injection of recombinant modified
      vaccinia virus Ankara strain was used to initiate a specific CTL response in mice
      capable of providing resistance to challenge with the murine melanoma B16.F10.
      Combining this immunotherapeutic regime with metronomic delivery of CTX resulted
      in antitumor activity that was dramatically enhanced over either treatment
      administered alone and was also significantly greater than combining
      immunotherapy with CTX administered by a maximum tolerated dose regime. Whereas
      both metronomic and maximum tolerated dose delivery of CTX did cause deletion of
      proliferating tumor-specific CTLs in the blood, this deletion occurred with
      slower kinetics with the metronomic schedule. Further analysis showed that
      metronomic CTX treatment did not delete cells with low expression of CD43, a
      "memory" phenotype, and that these cells maintained potent restimulatory
      capacity. The combination of immunotherapy and metronomic CTX therapy may be well
      suited to clinical management of cancer.

PMID- 14679004
TI  - Recombinant CD64-specific single chain immunotoxin exhibits specific cytotoxicity
      against acute myeloid leukemia cells.
AB  - CD64, the high affinity receptor for IgG (FcgammaRI) is expressed on acute
      myeloid leukemia blast cells and has recently been described as a specific target
      for immunotherapy. To generate a recombinant immunotoxin, the anti-CD64 single
      chain fragment (scFv) m22 was cloned into the bacterial expression vector pBM1.1
      and fused to a deletion mutant of Pseudomonas exotoxin A (ETA'). Genetically
      modified Escherichia coli BL21 Star (DE3) were grown under osmotic stress
      conditions in the presence of compatible solutes. After isopropyl beta-D
      thiogalactoside induction, the 70-kDa His(10)-tagged m22(scFv)-ETA' was directed
      into the periplasmic space and purified by a combination of metal-ion affinity
      and molecular size-chromatography. The characteristics of the recombinant protein
      were assessed by ELISA, flow cytometry, and toxicity assays, using CD64-positive
      AML cells. Binding specificity of m22(scFv)-ETA' was verified by competition with
      the parental anti-CD64 monoclonal antibody m22. The recombinant immunotoxin
      showed significant toxicity toward the CD64-positive cell lines HL-60 and U937
      reaching 50% inhibition of cell proliferation at a concentration (IC(50)) of 11.6
      ng/ml against HL-60 cells and 12.9 ng/ml against U937 cells. Approximately 41% of
      primary leukemia cells from a patient with CD64-positive AML were driven into
      early apoptosis by m22(scFv)-ETA' as measured by flow cytometric analysis. This
      is the first article documenting the specific cytotoxicity of a novel recombinant
      immunotoxin with major implications for immunotherapy of CD64-positive diseases.

PMID- 14679005
TI  - Coadministration of the heat shock protein 90 antagonist 17-allylamino- 17
      demethoxygeldanamycin with suberoylanilide hydroxamic acid or sodium butyrate
      synergistically induces apoptosis in human leukemia cells.
AB  - Interactions between the histone deacetylase inhibitors (HDACIs) suberoylanilide
      hydroxamic acid (SAHA) and sodium butyrate (SB) and the heat shock protein (Hsp)
      90 antagonist 17-allylamino-17-demethoxygeldanamycin (17-AAG) have been examined
      in human leukemia cells (U937). Coadministration of marginally toxic
      concentrations of 17-AAG with sublethal concentrations of SB or SAHA resulted in
      highly synergistic induction of mitochondrial damage (i.e., cytochrome c
      release), caspase-3 and -8 activation, and apoptosis. Similar interactions were
      noted in human promyelocytic (HL-60) and lymphoblastic (Jurkat) leukemia cells.
      These events were accompanied by multiple perturbations in signal transduction,
      cell cycle, and survival-related pathways, including early down-regulation of Raf
      1, inactivation of extracellular signal-regulated kinase (ERK) 1/2 and mitogen
      activated protein/ERK kinase (MEK) 1/2, diminished expression of phospho-Akt, and
      late activation of c-Jun-NH(2)-terminal kinase, but no changes in expression of
      phospho-p38 mitogen-activated protein kinase. Coadministration of 17-AAG blocked
      SAHA-mediated induction of the cyclin-dependent kinase inhibitor p21(CIP1) and
      resulted in reduced expression of p27(KIP1) and p34(cdc2). 17-AAG/SAHA-treated
      cells also displayed down-regulation of the antiapoptotic protein Mcl-1 and
      evidence of Bcl-2 cleavage. Enforced expression of doxycycline-inducible
      p21(CIP1) or constitutively active MEK1 significantly diminished 17-AAG/SAHA
      mediated lethality, indicating that interference with ERK activation and
      p21(CIP1) induction play important functional roles in the lethal effects of this
      regimen. In contrast, enforced expression of constitutively active Akt failed to
      exert cytoprotective actions. Together, these findings indicate that
      coadministration of SAHA or SB with the Hsp90 antagonist 17-AAG in human leukemia
      cells leads to multiple perturbations in signaling, cell cycle, and survival
      pathways that culminate in mitochondrial injury and apoptosis. They also raise
      the possibility that combining such agents with Hsp90 antagonists may represent a
      novel antileukemic strategy.

PMID- 14679006
TI  - Antitumor activity of lysophosphatidic acid acyltransferase-beta inhibitors, a
      novel class of agents, in multiple myeloma.
AB  - In this study, we examined the effects of isoform-specific functional inhibitors
      of lysophosphatidic acid acyltransferase (LPAAT), which converts lysophosphatidic
      acid to phosphatidic acid, on multiple myeloma (MM) cell growth and survival. The
      LPAAT-beta inhibitors CT-32176, CT-32458, and CT-32615 induced >95% growth
      inhibition (P < 0.01) in MM.1S, U266, and RPMI8226 MM cell lines, as well as MM
      cells from patients (IC(50), 50-200 nM). We further characterized this LPAAT-beta
      inhibitory effect using CT-32615, the most potent inhibitor of MM cell growth. CT
      32615 triggered apoptosis in MM cells via caspase-8, caspase-3, caspase-7, and
      poly (ADP-ribose) polymerase cleavage. Neither interleukin 6 nor insulin-like
      growth factor I inhibited CT-32615-induced apoptosis. Dexamethasone and
      immunomodulatory derivatives of thalidomide (IMiDs), but not proteasome inhibitor
      PS-341, augmented MM cell apoptosis triggered by LPAAT-beta inhibitors. CT-32615
      induced apoptosis was associated with phosphorylation of p53 and c-Jun NH(2)
      terminal kinase (JNK); conversely, JNK inhibitor SP600125 and dominant-negative
      JNK inhibited CT-32615-induced apoptosis. Importantly, CT-32615 inhibited tumor
      necrosis factor-alpha-triggered nuclear factor-kappaB activation but did not
      affect either tumor necrosis factor-alpha-induced p38 mitogen-activated protein
      kinase phosphorylation or interleukin 6-triggered signal transducers and
      activators of transcription 3 phosphorylation. Finally, although binding of MM
      cells to bone marrow stromal cells augments MM cell growth and protects against
      dexamethasone-induced apoptosis, CT-32615 induced apoptosis even of adherent MM
      cells. Our data therefore demonstrate for the first time that inhibiting LPAAT
      beta induces cytotoxicity in MM cells in the bone marrow milieu, providing the
      framework for clinical trials of these novel agents in MM.

PMID- 14679007
TI  - Nitric oxide-mediated signaling in the bystander response of individually
      targeted glioma cells.
AB  - Bystander responses have been reported to be a major determinant of the response
      of cells to radiation exposure at low doses, including those of relevance to
      therapy. In this study, human glioblastoma T98G cell nuclei were individually
      irradiated with an exact number of helium ions using a single-cell microbeam. It
      was found that when only 1 cell in a population of approximately 1200 cells was
      targeted, with one or five ions, cellular damage measured as induced micronuclei
      was increased by 20%. When a fraction from 1% to 20% of cells were individually
      targeted, the micronuclei yield in the population greatly exceeded that predicted
      on the basis of the micronuclei yield when all of the cells were targeted
      assuming no bystander effect was occurring. However when 2-(4-carboxyphenyl)
      4,4,5,5- tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), a nitric oxide (NO)
      specific scavenger was present in the culture medium, the micronuclei yields
      reduced to the predicted values, which indicates that NO contributes to the
      bystander effect. By using 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF
      FM), NO was detected in situ, and it was found that NO-induced fluorescence
      intensity in the irradiated population where 1% of cell nuclei were individually
      targeted with a single helium ion was increased by 1.13 +/- 0.02-fold (P < 0.005)
      relative to control with approximately 40% of the cells showing increased NO
      levels. Moreover, the medium harvested from helium ion-targeted cells showed a
      cytotoxic effect by inducing micronuclei in unirradiated T98G cells, and this
      bystander response was also inhibited by c-PTIO treatment. The induction of
      micronuclei in the population could also be decreased by c-PTIO treatment when
      100% of cells were individually targeted by one or two helium ions, indicating a
      complex interaction of direct irradiation and bystander signals.

PMID- 14679008
TI  - Glucuronidation as a mechanism of intrinsic drug resistance in human colon
      cancer: reversal of resistance by food additives.
AB  - Colon cancer exhibits inherent insensitivity to chemotherapy by mechanisms that
      are poorly characterized. We have shown that human colon cancer cells are
      efficient in drug conjugation catalyzed by UDP-glucuronosyltransferases (UGTs)
      and now report on the role of glucuronidation in de novo resistance to two
      topoisomerase I inhibitors. Identification of the UGT responsible for
      glucuronidation of SN-38 and the anthraquinone NU/ICRF 505 was achieved by first
      using a panel of human cDNA-expressed isozymes to measure conjugating activity.
      HT29 colon cancer cells were then probed by reverse transcriptase-PCR, Western
      Blot analysis, and liquid chromatography with mass spectrometry for their profile
      and activity of UGT isozymes and screened for effective inhibitors of
      glucuronidation. Expression analysis was also conducted in colon cancer biopsies
      and paired adjacent normal colon specimens. UGT1A9 was identified as the isozyme
      catalyzing biotransformation of the two compounds in HT29 cells and propofol as
      an effective competitive inhibitor of this metabolism. Inhibition of
      glucuronidation resulted in up to a 5-fold enhancement in drug activity. The
      majority of colon cancer biopsies studies expressed UGT protein at levels greater
      than in HT29 cells but with marked interpatient variations and proficiently
      glucuronidated the two anticancer drugs. A range of UGT aglycones were capable of
      modulating glucuronidation in the biopies with octylgallate being 10-fold more
      potent (ID(50) 24 microM) than propofol. In a subset of tumors (33%), UGT protein
      levels and activity exceeded that of paired normal colon. Glucuronidation may
      represent a mechanism of intrinsic drug resistance in colon cancer open to
      modulation by a range of food additives and proprietary medicines.

PMID- 14679009
TI  - Differential effects of rapamycin on mammalian target of rapamycin signaling
      functions in mammalian cells.
AB  - Rapamycin and its analogues have shown promising anticancer activities in
      preclinical and clinical studies. However, the mechanism whereby rapamycin
      inhibits signaling through the mammalian target of rapamycin (mTOR) remains
      poorly understood. Here, we show that the FKBP12/rapamycin complex is an
      essentially irreversible inhibitor of mTOR kinase activity in vitro. However, we
      observe no suppression of mTOR catalytic activity after immunoprecipitation from
      rapamycin-treated cells. These results suggest either that rapamycin acts as a
      reversible kinase inhibitor in intact cells or that the cellular effects of
      rapamycin are not mediated through global suppression in mTOR kinase activity. To
      better understand the cellular pharmacology of rapamycin, we compared the
      individual and combined effects of rapamycin and kinase-inactive mTOR expression
      on a panel of mTOR-dependent cellular responses. These studies identified
      glycolytic activity, amino acid transporter trafficking, and Akt kinase activity
      as novel, mTOR-modulated functions in mammalian cells. Whereas kinase-inactive
      mTOR did not enhance the decreases in cell size and glycolysis induced by
      rapamycin, expression of this mTOR mutant significantly enhanced the inhibitory
      effects of rapamycin on cell proliferation, 4EBP1 phosphorylation, and Akt
      activity. Unexpectedly, amino acid transporter trafficking was perturbed by
      kinase-inactive mTOR but not by rapamycin, indicating that this process is
      rapamycin insensitive. These results indicate that rapamycin exerts variable
      inhibitory actions on mTOR signaling functions and suggest that direct inhibitors
      of the mTOR kinase domain will display substantially broader anticancer
      activities than rapamycin.

PMID- 14679010
TI  - Tamoxifen DNA damage detected in human endometrium using accelerator mass
      spectrometry.
AB  - This study was aimed to establish whether tamoxifen binds irreversibly to uterine
      DNA when given to women. Patients were given a single therapeutic dose of
      [(14)C]tamoxifen citrate orally (20 mg, 0.37 or 1.85 MBq) approximately 18 h
      prior to hysterectomy or breast surgery. Nonmalignant uterine tissue was
      separated into myometrium and endometrium. DNA and protein were isolated and
      bound radiolabel determined by the sensitive technique of accelerator mass
      spectrometry. Levels of irreversible DNA binding of tamoxifen in the endometrium
      of treated patients were 237 +/- 77 adducts/10(12) nucleotides (mean +/- SE, n =
      10). In myometrial tissues, a similar extent of DNA binding was detected (492 +/-
      112 adducts/10(12) nucleotides). Binding of tamoxifen to endometrial and
      myometrial proteins was 10 +/- 3 and 20 +/- 4 fmol/mg, respectively. In breast
      tissue, sufficient DNA could not be extracted but protein binding was an order of
      magnitude higher than that seen with endometrial proteins (358 +/- 81 fmol/mg).
      These results demonstrate that after oral administration, tamoxifen forms adducts
      in human uterine DNA but at low numbers relative to those previously reported in
      women after long-term tamoxifen treatment where levels, when detected, ranged
      from 15000 to 130000 adducts/10(12) nucleotides. Our findings support the
      hypothesis that the low level of DNA adducts in human uterus is unlikely to be
      involved with endometrial cancer development.

PMID- 14679011
TI  - Radiotherapy potentiates the therapeutic efficacy of intratumoral dendritic cell
      administration.
AB  - We examined whether radiotherapy (RT) could enhance the efficacy of dendritic
      cell (DC)-based immunotherapy of cancer. Mice bearing s.c. D5 melanoma or MCA 205
      sarcoma tumors were treated with intratumoral (i.t.) injections of bone marrow
      derived unpulsed DCs in combination with local fractionated tumor irradiation. DC
      administration alone slightly inhibited D5 tumor growth and had no effect on MCA
      205. RT alone caused a modest inhibition of both tumors. DC administration
      combined with RT inhibited D5 and MCA 205 tumor growth in an additive and
      synergistic manner, respectively. In both tumor models, RT intensified the
      antitumor efficacy of DC administration independent of apoptosis or necrosis
      within the tumor mass. Combination treatment of i.t. DCs plus RT was superior to
      s.c. injections of tumor lysate-pulsed DCs plus interleukin 2 in inhibiting D5
      tumor growth and prolonging survival of mice. Splenocytes from mice treated with
      i.t. DCs plus RT contained significantly more tumor-specific, IFN-gamma-secreting
      T cells compared with control groups. Moreover, adoptive transfer of these
      splenocytes mediated significant tumor regression in mice bearing established
      pulmonary metastases. Combined treatment followed by resection of residual s.c.
      tumor conferred protective immunity against a subsequent i.v. tumor challenge.
      Furthermore, i.t. DC plus RT treatment of s.c. tumor in mice bearing concomitant
      pulmonary metastases resulted in a significant reduction of lung tumors. i.t. DC
      administration combined with RT induces a potent local and systemic antitumor
      response in tumor-bearing mice. This novel regimen may be beneficial in the
      treatment of human cancers.

PMID- 14679012
TI  - EphA2 as target of anticancer immunotherapy: identification of HLA-A*0201
      restricted epitopes.
AB  - EphA2 (Eck) is a tyrosine kinase receptor that is overexpressed in several human
      cancers such as breast, colon, lung, prostate, gastric carcinoma, and metastatic
      melanoma but not in nonmalignant counterparts. To validate EphA2 as a tumor
      antigen recognized by CD8+ T lymphocytes, we used reverse immunology approach to
      identify HLA-A*0201-restricted epitopes. Peptides bearing the HLA-A*0201-specific
      anchor motifs were analyzed for their capacity to bind and stabilize the HLA
      A*0201 molecules. Two peptides, EphA2(58) and EphA2(550), with a high affinity
      for HLA-A*0201 were selected. Both peptides were immunogenic in the HLA-A*0201
      transgenic HHD mice. Interestingly, peptide-specific murine CTLs cell lines
      responded to COS-7 cells coexpressing HLA-A*0201 and EphA2 and to EphA2-positive
      human tumor cells of various origin (renal cell, lung, and colon carcinoma and
      sarcoma). This demonstrates that EphA2(58) and EphA2(550) are naturally processed
      from endogenous EphA2. In addition, EphA2(58) and EphA2(550) stimulated specific
      CD8(+) T cells from healthy donor peripheral blood mononuclear cells. These T
      cells recognized EphA2-positive human tumor cells in an HLA-A*0201-restricted
      manner. Interestingly, EphA2-specific CD8+ T cells were detected in the
      peripheral blood mononuclear cells of prostate cancer patients. These results
      show for the first time that EphA2 is a tumor rejection antigen and lead us to
      propose EphA2(58) and EphA2(550) peptides for a broad-spectrum-tumor
      immunotherapy.

PMID- 14679013
TI  - CD4(+) T cells from healthy subjects and colon cancer patients recognize a
      carcinoembryonic antigen-specific immunodominant epitope.
AB  - The carcinoembryonic antigen (CEA) is an attractive target for immunotherapeutic
      purposes because of its expression profile, its role in tumor progression, and
      its immunogenicity. However, CEA belongs to the CD66 immunoglobulin super-gene
      family that comprises highly homologous molecules expressed on leukocytes, making
      CEA a potential autoantigen expressed on hematopoietic cells. We used a MHC class
      II epitope prediction algorithm (TEPITOPE) to select 11 sequence segments of CEA
      that could form promiscuous CD4(+) T-cell epitopes and used synthetic peptides
      corresponding to the predicted sequences to propagate in vitro CD4(+) T cells
      from healthy donors and colon cancer patients. CD4(+) T cells from all subjects
      strongly recognized the sequence segment (LWWVNNQSLPVSP), repeated at residues
      177-189 and 355-367. Importantly, we demonstrated that this highly immunodominant
      region contains a naturally processed epitope(s). Cross-recognition experiments
      with peptide analogues present on the CD66 homologous proteins showed that
      CEA(177-189/355-367)-specific CD4(+) T cells did not recognize the analogues,
      demonstrating that recognition of the immunodominant epitope is CEA specific.
      These data suggest that the repertoire of CEA(177-189/355-367)-specific CD4(+) T
      cells might have been shaped by a selective process to exclude CD4(+) T cells
      specific for CD66 homologues expressed on leukocyte, while preserving the CEA
      specific repertoire. The features of strong immunogenicity and immunodominance in
      the absence of potential induction of autoimmunity make the identified CEA
      epitope of particular interest for the development of antitumor vaccines.

PMID- 14679014
TI  - Immunotherapeutic targeting of shared melanoma-associated antigens in a murine
      glioma model.
AB  - Immune-based treatments for central nervous system gliomas have traditionally
      lagged behind those of more immunogenic tumors such as melanoma. The relative
      paucity of defined glioma-associated antigens that can be targeted by the immune
      system may partially account for this situation. Antigens present on melanomas
      have been extensively characterized, both in humans and in murine preclinical
      models. Melanocytes and astrocytes are both derived embryologically from the
      neural ectoderm. Their neoplastic counterparts, malignant melanomas and gliomas,
      have been shown in humans to share common antigens at the RNA level. However,
      little is known concerning whether gliomas can be targeted by immune-based
      strategies that prime T cells to epitopes from melanoma-associated antigens
      (MAAs). In this study, we provide evidence that two common murine glioma cell
      lines (GL26 and GL261) express the melanoma antigens gp100 and tyrosinase-related
      protein 2 (TRP-2). To understand the immunogenicity of murine gliomas to CD8(+) T
      cells, we examined the ability of a MAA-specific CTL cell line to lyse the glioma
      cells, as well as the in vivo expansion of MAA-specific CD8(+) T cells in animals
      harboring gliomas. Both glioma cell lines were lysed by a human gp100-specific
      CTL cell line in vitro. Mice harboring s.c. GL26 gliomas possessed TRP-2-specific
      CD8(+) T cells, providing further evidence that these gliomas express the protein
      products in the context of MHC class I. Furthermore, MAA peptide-pulsed dendritic
      cells could prime T cells that specifically recognize GL26 glioma cells in vitro.
      Lastly, mice that were prevaccinated with human gp100 and TRP-2 peptide-pulsed
      dendritic cells had significantly extended survival when challenged with tumor
      cells in the brain, resulting in >50% long-term survival. These results suggest
      that shared MAAs on gliomas can be targeted immunotherapeutically, pointing the
      way to a new potential treatment option for patients with malignant gliomas.

PMID- 14679015
TI  - Sequential action of phase I and II enzymes cytochrome p450 1B1 and glutathione S
      transferase P1 in mammary estrogen metabolism.
AB  - The Phase I enzyme cytochrome p450 1B1 (CYP1B1) has been postulated to play a key
      role in estrogen-induced mammary carcinogenesis by catalyzing the oxidative
      metabolism of 17beta-estradiol (E(2)) to catechol estrogens (2-OHE(2) and 4
      OHE(2)) and highly reactive estrogen quinones (E(2)-2,3-Q and E(2)-3,4-Q). The
      potential of the quinones to induce mutagenic DNA lesions is expected to be
      decreased by their conjugation with glutathione (GSH) either nonenzymatically or
      catalyzed by glutathione S-transferase P1 (GSTP1), a Phase II enzyme. Because the
      interaction of the Phase I and Phase II enzymes is not well defined in this
      setting, we prepared recombinant purified CYP1B1 and GSTP1 to examine their
      individual and combined roles in the oxidative pathway and used gas and liquid
      chromatography/mass spectrometry to measure the parent hormone E(2), the catechol
      estrogens, and the GSH conjugates. 2-OHE(2) and 4-OHE(2) did not form conjugates
      with GSH alone or in the presence of GSTP1. However, incubation of GSH and CYP1B1
      with 2-OHE(2) resulted in nearly linear conjugation through C-4 and C-1 (i.e., 2
      OHE(2)-4-SG and 2-OHE(2)-1-SG), whereas the reaction of 4-OHE(2) yielded only 4
      OHE(2)-2-SG. When CYP1B1 and GSTP1 were added together, the rate of conjugation
      was accelerated with a hyperbolic pattern of product formation in the order 4
      OHE(2)-2-SG > 2-OHE(2)-4-SG >> 2-OHE(2)-1-SG. Incubation of E(2) with CYP1B1 and
      GSTP1 resulted in the formation of 4-OHE(2), 2-OHE(2), 4-OHE(2)-2-SG, 2-OHE(2)-4
      SG, and 2-OHE(2)-1-SG. The production of GSH-estrogen conjugates was dependent on
      the concentrations of E(2) and GSTP1 but overall yielded only one-tenth of the
      catechol estrogen production. The concentration gap between catechol estrogens
      and GSH-estrogen conjugates may result from nonenzymatic reaction of the labile
      quinones with other nucleophiles besides GSH or may reflect the lower efficiency
      of GSTP1 compared with CYP1B1. In summary, both reactions are coordinated
      qualitatively in terms of product formation and substrate utilization, but the
      quantitative gap would leave room for the accumulation of estrogen quinones and
      their potential for DNA damage as part of estrogen-induced mammary
      carcinogenesis.

PMID- 14679016
TI  - Biological significance of aminopeptidase N/CD13 in thyroid carcinomas.
AB  - Aminopeptidase N (APN)/CD13 is a transmembrane ectopeptidase expressed on a wide
      variety of cells. However, the precise function of APN/CD13 in tumor cells and
      the relationship of APN/CD13 to thyroid cancer remain unclear. In our study, we
      quantified the expression of APN/CD13 and additionally dipeptidyl peptidase IV
      (DPIV)/CD26 in thyroid carcinoma cell lines and in tissues of patients with
      thyroid carcinomas. Undifferentiated anaplastic thyroid carcinomas expressed more
      APN/CD13 than differentiated thyroid carcinomas. DPIV/CD26 showed an opposite
      expression pattern. We detected higher levels of DPIV/CD26 in follicular thyroid
      carcinomas (FTCs) and papillary thyroid carcinomas than in undifferentiated
      anaplastic thyroid carcinomas. In the undifferentiated thyroid carcinoma cell
      line 1736, APN/CD13 mRNA expression could be increased by epidermal growth
      factor, basic fibroblast growth factor, interleukin-6, and tumor necrosis factor
      alpha. FTC-133 cells stably transfected with an expression vector for APN
      enhanced green fluorescent protein showed a higher migration rate than FTC-133
      cells transfected with the enhanced green fluorescent protein-control plasmid.
      Overexpression of APN/CD13 in stably transfected cells is associated with down
      regulation of N-myc down-regulated gene (NDRG)-1, melanoma-associated antigen
      ME491/CD63, and DPIV/CD26 gene expression. Inhibition of APN/CD13 mRNA expression
      by small interfering RNA induced NDRG-1, ME491/CD63, and DPIV/CD26 mRNA
      expression in cells of the undifferentiated thyroid carcinoma cell line C643. We
      conclude that APN/CD13-associated down-regulation of NDRG-1, ME491/CD63, and
      DPIV/CD26 in thyroid carcinoma cells is an important step of tumor progression to
      more malignant phenotypes, and we underline the important role of APN/CD13 as
      mediator in a multimolecular process regulating cell migration.

PMID- 14679017
TI  - Fine mapping of chromosome 3 in uveal melanoma: identification of a minimal
      region of deletion on chromosomal arm 3p25.1-p25.2.
AB  - To identify minimal common areas of allelic loss on chromosome 3, we have mapped
      both arms of the chromosome in 21 uveal melanomas that did not show monosomy 3 in
      our previous allelotype study. DNA was isolated from microdissected paraffin
      sections and amplified by PCR. In an initial screening, 14 microsatellite markers
      on chromosomal arm 3p and 13 on chromosomal arm 3q were used. Loss of
      heterozygosity for at least one marker was found in 9 of 21 tumors (43%) on 3p
      and 8 of 21 tumors (38%) on 3q. The initial analysis defined two common regions
      of allelic loss on 3p, a 7.3-Mb region between markers D3S1263 and D3S3510
      spanning 3p25.3-24.3 and a larger region between markers D3S1578 and D3S1284. The
      two common regions of allelic loss were further mapped with an additional 14
      microsatellite markers. A 1.4-Mb minimal region of allelic loss was identified
      between microsatellite markers D3S3610 and D3S1554 on 3p25.1-3p25.2. A total of
      10 tumors had allelic loss in this region; 2 of these tumors had corresponding
      putative homozygous deletions. These homozygous deletions may further narrow the
      region of interest to 0.1 Mb. This 1.4-Mb minimum region of deletion includes
      several genes that might be involved in the carcinogenesis of uveal melanoma as
      well as other important tumor types.

PMID- 14679018
TI  - Significance of MMP-2 expression in prostate cancer: an immunohistochemical
      study.
AB  - Prostate cancer is the most common cancer in North American men. Currently
      available prognostic factors inadequately predict which cancers will be
      aggressive and which will lead an indolent course. This study was aimed at
      investigating the role of matrix metalloproteinase (MMP)-2 in prostate cancer
      disease-free survival. We correlated MMP-2 expression by malignant prostatic
      epithelium and stromal cells with prostate cancer disease-free survival in 187
      stage pT3NxM0 prostate carcinomas using immunohistochemistry. MMP-2 was expressed
      by cancer cells in 131 cases (70.0%) and by stromal cells in 142 cases (75.9%).
      MMP-2 expression by stromal cells was not associated with progression (P =
      0.7270). However, in multivariate analyses, adjusting for the Gleason score,
      tumor-node-metastasis stage, and initial serum prostate-specific antigen, MMP-2
      expression by >50% of malignant epithelial cells was associated with decreased
      disease-free survival (hazard ratio, 4.267; P = 0.0012). Increased MMP-2
      expression by malignant prostatic epithelia is an independent predictor of
      decreased prostate cancer disease-free survival.

PMID- 14679019
TI  - Suppression of estrogen biosynthesis by procyanidin dimers in red wine and grape
      seeds.
AB  - In breast cancer, in situ estrogen production has been demonstrated to play a
      major role in promoting tumor growth. Aromatase is the enzyme responsible for the
      conversion of androgen substrates into estrogens. This enzyme is highly expressed
      in breast cancer tissue compared with normal breast tissue. A wine extract
      fraction was recently isolated from red wine that exhibited a potent inhibitory
      action on aromatase activity. Using UV absorbance analysis, high-performance
      liquid chromatography profiling, accurate mass-mass spectrometry, and nanospray
      tandem mass spectrometry, most of the compounds in our red wine fraction were
      identified as procyanidin B dimers that were shown to be aromatase inhibitors.
      These chemicals have been found in high levels in grape seeds. Inhibition kinetic
      analysis on the most potent procyanidin B dimer has revealed that it competes
      with the binding of the androgen substrate with a K(i) value of 6 micro M.
      Because mutations at Asp-309, Ser-378, and His-480 of aromatase significantly
      affected the binding of the procyanidin B dimer, these active site residues are
      thought to be important residues that interact with this phytochemical. The in
      vivo efficacy of procyanidin B dimers was evaluated in an aromatase-transfected
      MCF-7 breast cancer xenograft model. The procyanidin B dimers were able to reduce
      androgen-dependent tumor growth, indicating that these chemicals suppress in situ
      estrogen formation. These in vitro and in vivo studies demonstrated that
      procyanidin B dimers in red wine and grape seeds could be used as chemopreventive
      agents against breast cancer by suppressing in situ estrogen biosynthesis.

PMID- 14679020
TI  - Roscovitine inhibits STAT5 activity and induces apoptosis in the human leukemia
      virus type 1-transformed cell line MT-2.
AB  - T cells expressing human leukemia virus (HTLV) type 1, the etiological agent of
      adult T-cell leukemia, are remarkably resistant to conventional chemotherapy, and
      the need for drugs that effectively kill these cells is apparent. Here we show
      that roscovitine, an inhibitor of cyclin-dependent kinases (CDKs), induces the
      apoptosis of the HTLV-1-transformed T-cell line MT-2. Roscovitine prevented the
      tyrosine phosphorylation and consequent activation of the transcription factor
      signal transducer and activator of transcription (STAT) 5 when presented to MT-2
      cells in the presence or absence of a caspase-3 inhibitor, and ectopic expression
      of a dominant-negative form of STAT5 in MT-2 cells induced apoptosis. Roscovitine
      and dominant-negative STAT5 also reduced the expression of the antiapoptotic
      protein XIAP, and STAT5 was associated with the XIAP promoter in vivo. Antibody
      to platelet-derived growth factor (PDGF) alpha receptors coprecipitated STAT5
      from extracts of untreated but not roscovitine-treated cells. The tyrosine
      phosphatase inhibitor sodium orthovanadate ablated the inhibitory effects of
      roscovitine on STAT5/PDGF alpha receptor interaction, STAT5 activity, and cell
      survival. We suggest that roscovitine reduces the abundance of tyrosine
      phosphorylated PDGF alpha receptors; as a result, STAT5 does not become active,
      and STAT5 gene products required for cell survival are not expressed.

PMID- 14679021
TI  - Risk for smoking-related cancer among relatives of lung cancer patients.
AB  - Studies of familial aggregation of cancer provide indirect evidence for the role
      of genetic predisposition to cancer. In an ongoing case-control study, we
      evaluated whether first-degree relatives of lung cancer cases are at increased
      risk of lung and other cancers. Smoking-related cancers were defined as cancers
      of the lung, bladder, head and neck, kidney, and pancreas. The 806 probands
      included in this analysis were patients referred to The University of Texas M. D.
      Anderson Cancer Center (Houston, TX). We identified 663 controls, matched to the
      cases on age (+/-5 years), sex, ethnicity, and smoking history, who were
      recruited from a local multispecialty physician practice in the Houston
      metropolitan area. Self-reported cancer family history data were available for
      6430 first-degree relatives of the cases and 4936 first-degree relatives of the
      controls. An excess of cancer in relatives was evaluated by comparing the
      observed cancer cases among relatives of the cases with relatives of the
      controls. We conducted further analysis after stratifying on age of lung cancer
      onset (age at study registration for controls) and smoking status (never, former,
      or current) of the probands. We also conducted Cox regression analysis and
      compared time to cancer diagnosis among the relatives of the cases and controls
      adjusted for age and smoking status of proband and family members. Siblings
      [relative risk (RR) = 1.85; P = 0.003] of cases had a significant excess of lung
      cancer and an excess of smoking-related cancers (RR = 1.29; P = 0.01). We
      observed evidence of familial aggregation (RR = 1.71; P < 0.001) of lung cancer
      among relatives of late-onset lung cancer cases. From the Cox regression, we
      observed a moderate risk for development of lung (RR = 1.25; P = 0.09) and other
      smoking-related cancers (RR = 1.23; P = 0.05). After adjustment for smoking
      behavior of probands and their relatives, the risks of lung cancer (RR = 1.33; P
      = 0.03) and smoking-related cancers (RR = 1.28; P = 0.02) were statistically
      significant. We further stratified on age at onset and observed no evidence (P =
      0.81) of familial aggregation of lung cancer among young onset (<or=55 years of
      age) lung cancer cases. We also did not observe evidence of familial aggregation
      (P = 0.88) of smoking-related cancers in the same group. There was no evidence of
      increased risk (P = 0.77) of lung cancer among relatives of never-smokers. These
      findings support the need for additional study in the characterization and
      identification of genetic factors that influence and modulate cancer
      susceptibility in humans.

PMID- 14679022
TI  - A prospective study of XRCC1 haplotypes and their interaction with plasma
      carotenoids on breast cancer risk.
AB  - The XRCC1 protein is involved in the base excision repair pathway through
      interactions with other proteins. Polymorphisms in the XRCC1 gene may lead to
      variation in repair proficiency and confer inherited predisposition to cancer. We
      prospectively assessed the associations between polymorphisms and haplotypes in
      XRCC1 and breast cancer risk in a nested case-control study within the Nurses'
      Health Study (incident cases, n = 1004; controls, n = 1385). We further
      investigated gene-environment interactions between the XRCC1 variations and
      plasma carotenoids on breast cancer risk. We genotyped four haplotype-tagging
      single nucleotide polymorphisms (Arg(194)Trp, C26602T, Arg(399)Gln, and
      Gln(632)Gln) in the XRCC1 gene. Five common haplotypes accounted for 99% of the
      chromosomes in the present study population of mostly Caucasian women. We
      observed a marginally significant reduction in the risk of breast cancer among
      (194)Trp carriers. As compared with no-carriers, women with at least one (194)Trp
      allele had a multivariate odds ratio of 0.79 (95% of the confidence interval,
      0.60-1.04). The inferred haplotype harboring the (194)Trp allele was more common
      in controls than in cases (6.6 versus 5.3%, P = 0.07). We observed that the
      Arg(194)Trp modified the inverse associations of plasma alpha-carotene level (P,
      ordinal test for interaction = 0.02) and plasma beta-carotene level (P, ordinal
      test for interaction = 0.003) with breast cancer risk. No suggestion of an
      interaction was observed between the Arg(194)Trp and cigarette smoking. Our
      results suggest an inverse association between XRCC1 (194)Trp allele and breast
      cancer risk. The findings of the effect modification of the Arg(194)Trp on the
      relations of plasma alpha- and beta-carotene levels with breast cancer risk
      suggest a potential protective effect of carotenoids in breast carcinogenesis by
      preventing oxidative DNA damage.

PMID- 14679023
TI  - Interrelation of energy intake, body size, and physical activity with prostate
      cancer in a large prospective cohort study.
AB  - Energy restriction reduces prostate tumor growth in transplantable tumor models
      in rodents, which suggests that excessive energy intake may contribute to the
      risk of prostate cancer. The association of total energy intake across the normal
      range with prostate cancer has not been consistent in epidemiological studies. We
      prospectively evaluated the joint associations of energy intake and body size or
      physical activity with prostate cancer. Participants were 46786 male health
      professionals ages 40-75 years at baseline in 1986 who were free of cancer
      diagnosis. Between 1986 and 2000, we documented 2896 incident prostate cancer
      cases (excluding stage T1a) by review of medical records and histopathology
      reports. Of these, 339 were metastatic or fatal cases. We used Cox proportional
      hazards regression to estimate the multivariate relative risk (RR) of prostate
      cancer associated with energy intake measured using a food frequency
      questionnaire, overall and stratified by body mass index, waist size, physical
      activity, as well as by age and family history of prostate cancer. There was no
      association between energy intake and total prostate cancer incidence. However, a
      modest increased risk of metastatic or fatal disease with energy intake was
      suggested [RR comparing extreme quintiles: 1.38, 95% confidence interval (CI)
      0.96-1.98, P(trend) = 0.06]. This association was most pronounced in men with a
      lower body mass index (in stratum < 24 kg/m(2): RR = 1.76, 95% CI 0.92-3.39;
      P(interaction) = 0.04), smaller waist size [in stratum <or= 37 inches: RR = 1.91,
      95% CI 0.83-4.36; P(interaction) = 0.03], and who were more physically active [in
      stratum >or= median: RR = 1.74, 95% CI 0.93-3.26; P(interaction) = 0.09]. Also,
      the association of energy intake with metastatic and fatal prostate cancer was
      restricted to men who were younger [in stratum <or= 65 years old: RR = 2.60, 95%
      CI 1.26-5.39; P(interaction) = 0.04] or who had a positive family history [RR =
      3.33, 95% CI 1.26-8.76; P(interaction) = 0.04]. Although energy intake is known
      to be imperfectly measured by questionnaire, we observed a positive association
      between energy intake and metastatic or fatal prostate cancer among men who were
      leaner, more physically active, younger, and who had a family history of prostate
      cancer. Our observations suggest the testable hypothesis that the elevated risk
      of clinically important prostate cancer in men with a high energy intake may be
      attributable to certain metabolic profiles that favor enhanced growth factor
      production over an increase in adiposity.

PMID- 14679024
TI  - Polymorphism of the cyclin D1 gene, CCND1, and risk for incident sporadic
      colorectal adenomas.
AB  - Cyclin D1, encoded by the CCND1 gene and activated by the adenomatous polyposis
      coli-beta-catenin-T-cell factor/lymphoid enhancing factor pathway, induces G(1)
      to S-phase cell cycle transition, promoting cell proliferation. A recently
      described codon 242, exon 4, G to A single nucleotide polymorphism (A870G)
      produces a longer half-life cyclin D1. To investigate whether CCND1 genotype
      influences risk for colorectal adenoma, we genotyped CCND1 by PCR/RFLP on 161
      incident sporadic adenoma cases and 213 controls ages 30-74 years in a North
      Carolina colonoscopy-based case-control study. At least one polymorphic A allele
      was found in 68% of cases and 60% of controls. Having an A allele was associated
      with increased risk for adenoma: the age- and sex-adjusted odds ratio (OR) was
      1.5 [95% confidence interval (CI) 1.0-2.4], a finding that was stronger for those
      whose adenomas were multiple (OR 2.9, 95% CI 1.4-6.0), larger (>or=1 cm; OR 2.4,
      95% CI 1.2-4.8), had moderate to severe dysplasia (OR 2.1, 95% CI 1.1-3.8), or
      were in the right side of the colon (OR 3.6, 95% CI 1.3-10.0). Joint risk factor
      multivariate analyses revealed stronger positive associations among those who
      were older (>57 years; OR 2.8, 95% CI 1.4-5.5), male (OR 2.8, 95% CI 1.3-5.7),
      currently smoked (OR 2.7, 95% CI 1.3-5.7), or currently drank alcohol (OR 2.2,
      95% CI 1.2-4.2) if they had an A allele and stronger inverse associations among
      those who used nonsteroidal anti-inflammatory drugs (OR 0.4, 95% CI 0.2-0.9) or
      had higher calcium intakes (OR 0.4, 95% CI 0.2-0.9) if they had no A allele.
      These data support the hypothesis that the CCND1 A870G polymorphism may increase
      risk for colorectal neoplasms.

PMID- 14679025
TI  - Correspondence re: L. M. Wein et al., validation and analysis of a mathematical
      model of a replication-competent oncolytic virus for cancer treatment:
      implications for virus design and delivery. Cancer Res., 63: 1317-1324, 2003.

PMID- 14679026
TI  - Correspondence re: S. Maula et al., intratumoral lymphatics are essential for the
      metastatic spread and prognosis in squamous cell carcinoma of the head and neck.
      Cancer Res., 63: 1920-1926, 2003.

PMID- 14679027
TI  - Correspondence re: H. Barthel et al., 3'-deoxy-3'-[(18)F]fluorothymidine as a new
      marker for monitoring tumor response to antiproliferative therapy in vivo with
      positron emission tomography. Cancer Res., 63: 3791-3798, 2003.

PMID- 14679031
TI  - Encephalitis lethargica: part of a spectrum of post-streptococcal autoimmune
      diseases?

PMID- 14679032
TI  - SCA19 and SCA22: evidence for one locus with a worldwide distribution.

PMID- 14679035
TI  - The second murine autoantibody workshop: remarkable interlaboratory concordance
      for radiobinding assays to identify insulin autoantibodies in nonobese diabetic
      mice.
AB  - In October 2000, the First Murine Autoantibody Workshop was held as part of an
      International Workshop on Lessons from Animal Models for Human Type 1 Diabetes.
      This first workshop identified insulin, but not glutamic acid decarboxylase (GAD)
      or IA-2, as specific autoantigens of humoral immunity in nonobese diabetic (NOD)
      mice. The goals of the Second Murine Autoantibody Workshop, part of the Sixth
      Annual Meeting of the IDS, were to increase the number of participating
      investigators, attempt standardization of insulin autoantibody (IAA) results
      across laboratories, identify serologic evidence of humoral immunity to other
      beta cell antigens, and allow for validation of ELISA assays for autoantibody
      detection in NOD mice. Sixty-three coded samples (26 pooled NOD sera, 23 pooled
      C57BL/6 sera, and 14 diluted samples of an anti-insulin monoclonal antibody) were
      distributed to 12 participating laboratories. This second workshop demonstrated
      that, for nearly all laboratories, IAA measured by radioimmunoassay (RIA)
      provided a sensitive and specific assay capable of distinguishing diabetes-prone
      from nondiabetes-prone mice. Analyses involving the serially diluted anti-insulin
      monoclonal antibody offered hope that a standard reference unit for reactivity
      could be established. Surprisingly, two ELISA assays for IAA detection proved
      remarkably sensitive (i.e., 65% and 92%). However, subsequent absorption studies
      performed after the workshop (presented at the IDS meeting) brought into question
      whether ELISA assays for IAA do, in reality, detect anti-insulin immunities and
      whether assays for GAD and IA-2 autoantibodies distinguish diabetes-prone from
      nondiabetes-prone mice. In sum, this workshop continued to support the notion
      that IAA, as determined by RIA, could provide a sensitive and specific marker of
      anti-beta cell immunity in NOD mice.

PMID- 14679036
TI  - Can enteroviruses cause type 1 diabetes?
AB  - Enterovirus infections have long been considered as one possible environmental
      trigger of type 1 diabetes. These viruses have been detected from diabetic
      patients more often than from control subjects and they can infect beta cells in
      cell culture and induce diabetes in animal models. Furthermore, a same kind of
      seasonality has been observed in both the onset of clinical diabetes and
      subclinical beta cell autoimmunity (appearance of autoantibodies) as in
      enterovirus infections. Recently, considerable new evidence has cumulated from
      prospective studies indicating the risk effect of enterovirus infections long
      before clinical diabetes was diagnosed. In addition, several studies have
      reported enterovirus genome sequences in diabetic patients more often than in
      control subjects. Currently, the evidence for the role of enteroviruses is
      stronger than for most other environmental agents, but still the final proof is
      lacking. The ongoing studies aim to prove the risk effect in different
      populations and to identify the underlying mechanisms. This research field is
      becoming more and more important because it could open up possibilities to
      prevent type 1 diabetes by an enterovirus vaccine.

PMID- 14679037
TI  - Establishing evidence for enterovirus infection in chronic disease.
AB  - Viruses have long been considered among potential environmental triggers of type
      1 diabetes mellitus. Epidemiologic and seroprevalence studies have associated
      enterovirus infection with development of prediabetic autoimmunity and with the
      onset of clinical diabetes. Enterovirus infection has also been temporally
      correlated with disease onset by virus isolation or by detection of viral genome
      by reverse transcription-polymerase chain reaction (RT-PCR). For the large-scale
      prospective studies that are required to firmly establish a causal relationship
      between enterovirus infection and development of prediabetic autoimmunity or
      progression from autoimmunity to clinical diabetes, sensitive RT-PCR methods must
      be used to detect virus prior to the onset of diabetic symptoms. We have
      developed an RT-seminested PCR protocol to detect enteroviruses in clinical
      specimens. This method is approximately 10,000-fold more sensitive than
      conventional, single-amplification PCR. Further, we have developed molecular
      methods to rapidly and reliably identify enterovirus serotype, bypassing the
      cumbersome and often problematic neutralization test. The molecular serotyping
      approach will be valuable in examining the relationships between particular virus
      serotypes or genotypes and specific diseases.

PMID- 14679038
TI  - Beta cell death and protection.
AB  - Type 1 diabetes is an immune-mediated disease critically dependent upon the
      interaction between antigen-presenting cells and T cells. Clearly, both CD4+ and
      CD8+ T cells are required, but activated CD4+ T cells are both necessary and
      sufficient in causing disease. The mechanism of the Th1/Th2 immunoregulatory
      imbalance is unclear and needs to be further investigated. CD8+ T cells are not
      commonly sufficient in causing disease, but CD8 T cells are necessary in
      initiation (<14 weeks in the NOD mouse), but not in the later (>14 weeks)
      effector phase of the disease. It is still unclear whether the CD8+ T cell exerts
      its function as a classical effector cell or mainly as an immunomodulatory cell
      acting in synergy with the CD4+ T cell. The relative role of T cell effector
      mechanisms such as Fas/FasL, perforin/granzyme, and the TRAIL systems is unclear.
      Proinflammatory cytokines, reactive oxygen species, and other immune mediators
      seem to be involved in beta cell destruction, but much is to be learned about
      signaling, molecular mechanisms, and in vivo importance.

PMID- 14679039
TI  - Oxidative stress in type 1 diabetes.
AB  - We have been investigating the effects of preventing oxidative stress on
      pathogenesis and complications of type 1 diabetes in the NOD mouse model. Our
      studies have shown that damage caused by oxidative stress is higher in islets and
      vascular tissue of NOD mice than in nonautoimmune controls or a diabetes
      resistant NOD mouse. In addition, phagocytic function and cytokine production by
      macrophages are aberrant in the NOD. We have demonstrated that treatment of
      prediabetic NOD mice for 2 weeks with a metalloporphyrin superoxide dismutase
      (SOD) mimetic results in marked reduction of oxidative stress in islets and
      vascular tissue and a reversal of macrophage defects.

PMID- 14679040
TI  - Use of microarray analysis to unveil transcription factor and gene networks
      contributing to Beta cell dysfunction and apoptosis.
AB  - The beta cell fate following immune-mediated damage depends on an intricate
      pattern of dozens of genes up- or downregulated in parallel and/or sequentially.
      We are utilizing microarray analysis to clarify the pattern of gene expression in
      primary rat beta cells exposed to the proapoptotic cytokines, IL-1beta and/or IFN
      gamma. The picture emerging from these experiments is that beta cells are not
      passive bystanders of their own destruction. On the contrary, beta cells respond
      to damage by activating diverse networks of transcription factors and genes that
      may either lead to apoptosis or preserve viability. Of note, cytokine-exposed
      beta cells produce and release chemokines that may contribute to the homing and
      activation of T cells and macrophages during insulitis. Several of the effects of
      cytokines depend on the activation of the transcription factor, NF-kappaB. NF
      kappaB blocking prevents cytokine-induced beta cell death, and characterization
      of NF-kappaB-dependent genes by microarray analysis indicated that this
      transcription factor controls diverse networks of transcription factors and
      effector genes that are relevant for maintenance of beta cell differentiated
      status, cytosolic and ER calcium homeostasis, attraction of mononuclear cells,
      and apoptosis. Identification of this and additional "transcription factor
      networks" is being pursued by cluster analysis of gene expression in insulin
      producing cells exposed to cytokines for different time periods. Identification
      of complex gene patterns poses a formidable challenge, but is now technically
      feasible. These accumulating evidences may finally unveil the molecular
      mechanisms regulating the beta cell "decision" to undergo or not apoptosis in
      early T1DM.

PMID- 14679041
TI  - The T cell response to glutamic acid decarboxylase 65 in T cell receptor
      transgenic NOD mice.
AB  - Using BW 5147 T cell hybridomas isolated by fusion with spleen and lymph node
      cells from NOD female mice, two T cell receptor transgenic NOD mouse lines were
      produced. Both TCR transgenics respond to their cognate peptide/MHC (GAD65 206
      220 and 286-300) and produce IL-2, IFN-gamma, and small amounts of IL-10.
      Unexpectedly, the transgenic mice do not develop diabetes and have no insulitis.
      Analysis with a GAD65 286-300/I-A(g7) tetramer reveals that transgenic T cells
      are negatively selected in the thymus and further negatively selected in the
      periphery. When crossed to the C(alpha)(-/-) NOD line, CD4 T cells were reduced
      by 90% in the thymus and periphery. Further, the tetramer positive GAD65 286-300
      specific T cells were capable of delaying the onset of diabetes in a standard
      transfer system. Thus, GAD65 specific TCR transgenic T cells (1) must express a
      second a chain to survive negative selection, (2) produce IL-2 and IFN-gamma, and
      (3) have a mildly protective effect on transfer of diabetes with diabetogenic
      spleen cells.

PMID- 14679042
TI  - Detection of CD4+ autoreactive T cells in T1D using HLA class II tetramers.
AB  - The use of soluble class II MHC tetramers has enabled the identification of
      autoantigen-specific T cells in the peripheral blood of type 1 diabetes patients.
      Our approach takes advantage of the appearance of highly activated T cells
      expressing a CD25(+)/CD4(high+) phenotype induced by immobilized class II MHC
      monomer containing the GAD65 peptide. Almost all T cells that stain with the
      specific tetramer reside in this population and, since this activation profile is
      not present in normal subjects, it may provide a useful tool for analysis of the
      T cell response in autoimmune diabetes. The utilization of tetramer techniques in
      the detection of autoreactive T cells is a powerful tool to gain insight into
      mechanisms of the molecular basis of autoimmunity. The phenotyping of T cells
      should provide useful markers for progression of immune-mediated beta cell
      reactivity and can be utilized in clinical trials to evaluate the efficacy of the
      immunomodulatory therapies targeting intervention/prevention of autoimmune
      diseases.

PMID- 14679043
TI  - Kinetic evolution of a diabetogenic CD8+ T cell response.
AB  - Nonobese diabetic (NOD) mice develop overt diabetes following prolonged periods
      of pancreatic islet inflammation involving both CD4+ and CD8+ T cells. The
      initiation and progression of autoimmune diabetes require the recruitment of beta
      cell-reactive CD8+ T cells to the pancreatic lymph nodes, their activation by
      antigen, and their subsequent migration into pancreatic islets. We and others
      have shown that a significant fraction of NOD islet-associated CD8+ T cells
      express highly homologous TCRalpha chains (Valpha17 and Jalpha42 joined by the
      same N-region sequence) and that they recognize the peptide NRP-A7 in the context
      of the MHC class I molecule H-2K(d). We have also shown that this T cell
      subpopulation undergoes a process of "avidity maturation" that is associated with
      progression of benign insulitis to overt diabetes. This paper will summarize our
      current understanding of the mechanisms that drive the recruitment and activation
      of this CD8+ T cell subpopulation.

PMID- 14679044
TI  - Multiple and high-titer single autoantibodies in schoolchildren reflecting the
      genetic predisposition for type 1 diabetes.
AB  - The study aimed to compare the HLA specificities of AAb-positive healthy
      schoolchildren with those of patients with type 1 diabetes (T1D). HLA-DRB1 and
      DQB1 alleles were determined in 178 AAb-positive and 339 AAb-negative
      schoolchildren aged 6-17 years without first-degree relatives with T1D and in 274
      patients with T1D. AAbs against glutamic acid decarboxylase (GADA), protein
      tyrosine phosphatase (IA-2A), and insulin (IAA) were determined by (125)I-antigen
      binding, and islet cell cytoplasmic antibodies (ICAs) immunohistochemically.
      Here, 82.6% (147/178) of AAb-positive schoolchildren had single AAbs and 17.4%
      (31/178) had multiple AAbs. In both groups, GADA occurred with highest and IAA
      with lowest frequency. In children with single AAbs at levels between the 99th
      and 99.9th percentile, frequencies of the diabetes-associated DRB1 (*03, *04) and
      DQB1 (*02, *0302) alleles and the protective DRB1 (*15) and DQB1 (*0602) alleles
      did not differ from those of controls. In patients, the positive associations
      were confirmed for DRB1*04 (OR = 5.39) and DQB1*0302 (OR = 9.05), whereas DRB1*15
      (OR = 0.05) and DQB1*0602 (OR = 0.06) were negative-associated (p < 0.001). The
      same association was found in schoolchildren with multiple AAbs for DRB1*04 (OR =
      3.84), DQB1*0302 (OR = 4.95), and DRB1*15 (OR = 0.1; p < 0.001-0.014), and with
      high-titer single AAbs (>/=99.9th percentile), but none of them had DQB1*0602.
      The highest risk genotype DQB1*02/*0302 occurred in 36.5% of patients (OR =
      21.07) and in 19.3% of children with multiple AAbs (OR = 8.8; p<0.001). It is
      concluded that probands with multiple and high-titer single AAbs in the general
      population have the same genetic predisposition for T1D as patients and are
      therefore at highest risk for the disease.

PMID- 14679045
TI  - Insulin autoimmunity: immunogenetics/immunopathogenesis of type 1A diabetes.
AB  - We can now predict the development of type 1A diabetes in humans and prevent the
      disorder in animal models, but we cannot at present safely prevent type 1A
      diabetes in humans, although a series of clinical trials are under way and
      planned. A major lack in our current trial design is the inability to measure T
      lymphocytes directly responsible for beta cell destruction. Given the
      immunogenetics of type 1A diabetes and increasing knowledge of pathogenesis in
      the NOD mouse, we believe the disorder results from immune reactivity to a
      limited set of islet peptides, with reactivity to insulin a major determinant of
      disease. Insulin autoantibodies precede the development of diabetes in both
      humans and the NOD mouse. T lymphocytes isolated from the islets of the NOD mouse
      that recognize insulin peptide B:9-23 can transfer diabetes. Insulin expression
      within the thymus is correlated with genetic susceptibility, and insulin peptides
      can be used to induce diabetes and as an immunologic vaccine to prevent the
      disorder. Nevertheless, at present, routine measurement of anti-insulin T
      lymphocytes is not standardized. Better assays to monitor such autoreactivity are
      likely to be essential for the development and evaluation of preventive
      therapies.

PMID- 14679046
TI  - MHC-linked susceptibility to type 1 diabetes: a structural perspective.
AB  - The MHC represents the most important susceptibility locus for type 1 diabetes,
      and the MHC class II alleles that encode DQ8 and DQ2 in humans and I-A(g7) in NOD
      mice represent critical elements. Even though these genetic facts have been known
      for a number of years, the biochemical and structural features of these MHC class
      II molecules have only been elucidated recently. We expressed DQ8 and I-A(g7) as
      soluble proteins and observed significant structural and functional similarities
      between these human and murine MHC molecules. It had been postulated that I-A(g7)
      and DQ8 are poor peptide binders, based on the observation that the subunits
      dissociate in the presence of SDS, a denaturing detergent. We observed that both
      DQ8 and I-A(g7) form stable, long-lived complexes with a number of different
      peptides, indicating that they are not unstable in the absence of detergent. DQ8
      and I-A(g7) were found to bind similar sets of peptides, which included peptides
      that had been identified as immunodominant T cell epitopes of insulin and GAD 65
      in NOD mice. The insulin B (9-23) peptide formed long-lived complexes with DQ8
      and was thus chosen for crystallization of the complex. No defect in the peptide
      binding groove was evident in the crystal structure and the insulin peptide was
      deeply anchored in the binding site. The structure demonstrated significant
      similarities between DQ8 and I-A(g7), indicating that similar antigen
      presentation events are relevant in the NOD mouse model and the human disease.

PMID- 14679047
TI  - Using regulatory APCs to induce/maintain tolerance.
AB  - It is well established that antigen-presenting cells (APCs) such as dendritic
      cells (DCs) possess potent immune-stimulatory function. They are considered to be
      the key driving element for most immune, autoimmune, and host-defense responses.
      However, recent evidence suggests that as much as APCs can turn things on, they
      also have the capability to turn things off. To summarize the evidence for such
      regulatory function of APCs is the purpose of this review article. We are just
      beginning to understand whether regulatory APC function can be mapped to a
      separate lineage of APCs or whether it is more commonly acquired under certain
      maturation conditions. Furthermore, it becomes apparent that it is important to
      consider differences between human and mouse DCs as well as splenic-, lymph node
      , or blood-derived APCs. We believe that, in the upcoming years, better
      understanding of positive and negative roles of APCs in immune regulation will
      benefit both sides of APC therapy: their use in enhancing immunity, for example,
      in vaccine design and cancer, as well as their application for the treatment of
      autoimmunity.

PMID- 14679048
TI  - Cell-based therapies for diabetes: progress towards a transplantable human beta
      cell line.
AB  - Achieving normoglycemia is the goal of diabetes therapy. Potentially, there are
      many ways to achieve this goal, including transplantation of cells exhibiting
      glucose-responsive insulin secretion. However, to be applicable to the large
      number of people who might benefit from beta cell replacement, an unlimited
      supply of beta cells must be found. To address this problem, we have been
      developing cell lines from the human endocrine pancreas. In one case, a cell
      line, betalox5, has been developed from human islets that can be induced under
      some circumstances to differentiate into functional beta cells exhibiting
      appropriate glucose-responsive insulin secretion. Inducing differentiation is
      complex, requiring the activation of multiple signaling pathways, including those
      downstream of those involved in cell-cell contact and the glucagon-like peptide-1
      receptor. In addition, transfer of the PDX-1 gene is also necessary to render the
      cells competent for differentiation. However, it is clear that many other genes
      are involved in maintaining the commitment of betalox5 cells towards the beta
      cell lineage. Understanding the complement of genes required to establish and
      maintain a beta cell lineage commitment would be enormously helpful in efforts to
      develop a cell line that can be used for beta cell replacement therapies. Here,
      we provide further information on the characteristics of cell lines that we have
      developed from the human pancreas that are relevant to the development of a beta
      cell replacement therapy for diabetes.

PMID- 14679049
TI  - Islet cell autoimmunity and transplantation tolerance: two distinct mechanisms?
AB  - Recent advances in islet transplantation have enabled physicians to cure type 1
      autoimmune diabetes, but at the cost of lifelong immunosuppression with its
      attendant side effects and long-term health risks. To eliminate the need for
      immunosuppression, researchers have developed methods for inducing tolerance to
      transplanted allografts. Tolerance-based transplantation using costimulation
      blockade has proven remarkably successful in many animal model systems. The most
      widely used animal model system for studying islet transplantation in type 1-like
      autoimmune diabetes is the NOD mouse. Unfortunately, this strain has proven
      resistant to costimulation blockade-based transplantation tolerance protocols
      that are successful in chemically diabetic mice given islet grafts. It has been
      assumed that resistance to transplantation tolerance in the NOD mouse is (1)
      related to autoimmunity directed against its pancreatic beta cells, (2) a
      consequence of that autoimmunity, and (3) under the control of the same genes
      that control autoimmunity. In this review, we provide arguments to challenge
      these assumptions. We describe a new animal model and a new conceptual framework
      based on data indicating that the mechanisms responsible for resistance to
      transplantation tolerance and beta cell autoimmunity are not identical. We
      believe that the recent discoveries we describe will have important implications
      for the development of tolerance-based transplantation therapies and their
      translation from the laboratory to the clinic.

PMID- 14679050
TI  - Characterization of early developments in the splenic leukocyte transcriptome of
      NOD mice.
AB  - Transcriptome analysis is a powerful tool to characterize changes in leukocyte
      gene expression patterns and reveal very early molecular abnormalities in tissue.
      Herein, we report on characterization of the very earliest abnormalities in the
      transcriptome of leukocytes from young "prepathologic" NOD and NON female mice.

PMID- 14679051
TI  - Autoimmune diabetes in the NOD mouse: an essential role of Fas-FasL signaling in
      beta cell apoptosis.
AB  - Despite evidence that both Fas and FasL can be expressed in pancreatic islets,
      there has been considerable controversy regarding the potential role of Fas
      signaling in autoimmune beta cell death. Using the HIPFasL model, we have been
      able to demonstrate that, in the presence of an inflammatory infiltrate, FasL
      expressing beta cells are exquisitely sensitive to Fas-mediated apoptosis and
      that this can be blocked by preventing FasL-Fas interaction. This points to a
      highly important role of Fas-FasL interaction in autoimmune beta cell death.

PMID- 14679052
TI  - Fas and Fas ligand immunoexpression in pancreatic islets of NOD mice during
      spontaneous and cyclophosphamide-accelerated diabetes.
AB  - During insulin-dependent diabetes mellitus, beta cell destruction may involve
      activation of the Fas-Fas ligand (Fas-FasL) system. Here, we employed dual-label
      immunohistochemistry to examine the intra-islet expression, distribution, and
      cellular sources of Fas and FasL in the NOD mouse. Pancreatic tissues were
      studied during spontaneous diabetes (days 21, 40, and 90) and following
      acceleration of diabetes with cyclophosphamide (days 0, 4, 7, 11, and 14 after
      cyclophosphamide administration). Our results show that FasL was expressed
      constitutively in most beta cells of NOD mice and in nondiabetes-prone mice, but
      not in glucagon or somatostatin cells or in islet inflammatory cells. It
      paralleled the loss of insulin immunolabeling with advancing disease.
      Immunolabeling for Fas was first observed in extra-islet macrophages and those
      close to the islet in NOD and nondiabetes-prone mice. During spontaneous and
      cyclophosphamide diabetes, it was observed in a higher proportion of islet
      infiltrating macrophages than in CD4 and CD8 cells. In the cyclophosphamide
      group, Fas expression in intra-islet CD4 and CD8 cells showed an increase close
      to the onset of diabetes. At days 11 and 14, several intra-islet macrophages with
      immunolabeling for Fas also coexpressed interleukin-1beta and inducible nitric
      oxide synthase. Fas was not detected in beta cells and other endocrine cells
      during spontaneous and cyclophosphamide diabetes. We show constitutive expression
      of FasL in beta cells in the NOD mouse and predominant expression of Fas in intra
      islet macrophages and to a lesser extent in T cells prior to diabetes onset. The
      role of Fas-FasL in beta cell destruction in the NOD mouse requires further
      clarification.

PMID- 14679053
TI  - Type 1 diabetes in Swedish bank voles (Clethrionomys glareolus): signs of disease
      in both colonized and wild cyclic populations at peak density.
AB  - Colonized bank voles (Clethrionomys glareolus) originating from Sweden developed
      type 1 diabetes. Animals became polydipsic, glucosuric, and hyperglycemic and
      gradually developed a lethal ketoacidosis. Pancreas in animals with end-stage
      disease showed total destruction of islet cells. Interestingly, also a high
      proportion of wild bank voles in cyclic populations that were trapped at (or
      close to) the cyclic population density peak frequently showed high blood glucose
      levels and pathological glucose tolerance test. Extensive islet destruction was
      not seen in wild bank voles at the time of capture, but did develop in some of
      the animals over a time period of two months. Diabetes in both colonized and wild
      bank voles was associated with Ljungan virus (LV). LV could be isolated from the
      pancreas of diabetic bank voles and antigen detected at the site of tissue damage
      by immunohistochemistry. In addition, picornavirus-like particles were visualized
      in the islets of diabetic voles using thin-section transmission electron
      microscopy.

PMID- 14679054
TI  - Defective activation-induced cell death in NOD T lymphocytes: 1,25
      dihydroxyvitamin D3 restores defect.
AB  - The aim of this study was first to analyze strain differences in apoptosis
      resistance of NOD peripheral T lymphocytes in in vitro models of death by neglect
      and activation-induced cell death (AICD). Especially AICD is known to play a key
      role in peripheral tolerance, keeping autoimmune effector cells under control.
      Second, we studied the effects of in vivo treatment of NOD mice with 1alpha,25
      dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], an immunomodulator known to prevent
      diabetes and insulitis in NOD mice, on in vitro T lymphocyte apoptosis
      resistance.

PMID- 14679055
TI  - The role of endoplasmic reticulum stress in nonimmune diabetes: NOD.k iHEL, a
      novel model of beta cell death.
AB  - The final common pathway in diabetes development is beta cell apoptosis. We
      herein describe a novel diabetes model based on transgenic NOD.k iHEL mice,
      wherein male mice develop diabetes due to nonimmune-mediated beta cell death.
      Histology and electron microscopy confirm endoplasmic reticulum (ER)
      abnormalities that are consistent with endoplasmic stress caused by the HEL
      transgene. The NOD.k iHEL model may be particularly useful for studying
      mechanisms of beta cell death secondary to ER stress and also for testing
      potential therapies designed to protect beta cells from stress-induced apoptosis.
      The observation that only male NOD.k iHEL mice develop diabetes and exhibit ER
      abnormalities is intriguing and suggests these mice may be useful in deciphering
      the link between hyperandrogenism, insulin resistance, and diabetes.

PMID- 14679056
TI  - Defective maturation of myeloid dendritic cell (DC) in NOD mice is controlled by
      IDD10/17/18.
AB  - We previously demonstrated that adoptive transfer of NOD pancreatic lymph node
      (PLN) DC protected recipients from diabetes. Our recent studies showed that the
      tolerogenic DC population presented islet antigens and were mature myeloid DC
      that did not produce IL-12, suggestive of exhausted or fully mature DC. Extensive
      characterization of the DC population in vivo in NOD and control mice
      demonstrated a specific deficiency of PLN tolerogenic DC in older mice. These
      findings suggest autoimmunity might arise in NOD mice secondary to deficient
      maturation of myeloid DC to a tolerogenic state. To address this issue, we
      characterized maturation and function at development of bone marrow-derived
      myeloid DC from NOD and several control strains. We found that NOD DC were highly
      resistant to several maturation stimuli and maintained an immature phenotype
      (average % immature DC: 75% in NOD versus 15% in B6, p < 0.01). A survey of
      congenic NOD mice with various NOD diabetes susceptibility loci demonstrated that
      the IDD10/17/18 region on chromosome 3 controlled approximately 50% of the NOD DC
      maturation defect. The defect also affected NOD DC that underwent phenotypic
      maturation. These cells appeared to arrest in a "maturing" phase as they produced
      5- to 7-fold more IL-12 than control strains and significantly less IL-10. The
      cytokine defect was completely corrected in NOD IDD10/17/18 mice. In addition,
      the IDD10/17/18 locus limited DC accumulation in islets and significantly
      increased tolerogenic DC in the PLN. Together, the above findings suggest that
      polygenic regulation of DC maturation defects in NOD mice promotes islet
      inflammation while limiting the generation of tolerogenic DC.

PMID- 14679057
TI  - Absence of the T-bet gene coding for the Th1-related transcription factor does
      not affect diabetes-associated phenotypes in Balb/c mice.
AB  - The T-box expressed in T cells gene (T-bet) is a member of the T-box family of
      transcription factors. T-bet-deficient mice show normal lymphoid development, but
      exhibit profound defects in their Th1-mediated immune responses. As the balance
      between Th1- and Th2-mediated immune responses plays a role in autoimmune-prone
      diseases, we have investigated the diabetes-related insulin autoantibody (IAA)
      and cellular immune responses (insulitis), in the absence of Th1 lineage
      commitment, in T-bet KO Balb/c mice, after immunization with the B9-23 insulin
      peptide. We have therefore investigated whether absence of the T-bet gene
      influences diabetes-related phenotypes in Balb/c T-bet KO mice.

PMID- 14679058
TI  - Immunolocalization of caspase-3 in pancreatic islets of NOD mice during
      cyclophosphamide-accelerated diabetes.
AB  - Apoptosis may be a major mechanism of beta cell loss during insulin-dependent
      diabetes mellitus. Caspase-3 is a key enzyme involved in the terminal steps of
      this death process. Here, the intra-islet expression of caspase-3 in the NOD
      mouse was examined immunohistochemically following acceleration of the disease
      with cyclophosphamide. Female NOD mice were treated at day 95 with
      cyclophosphamide, and caspase-3 expression in pancreatic sections was studied at
      days 0, 4, 7, 11, and 14 and compared with age-matched control tissue. In the
      treated group at day 0, caspase-3 labeling was seen in several peri-islet
      macrophages and only extremely rarely in beta cells. At day 4, only a few beta
      cells weakly expressed the enzyme. From day 7, caspase-3 expression began to
      increase in intra-islet macrophages and reached a peak at days 11 and 14, when a
      small number of CD4 and CD8 T cells also showed positive labeling. Beta cell
      expression of caspase-3 at days 11 and 14 was rare. At this stage, several intra
      islet immune cells with positive labeling for the enzyme coexpressed either Fas
      or interleukin-1beta. Only a small proportion of intra-islet caspase-3 cells
      showed apoptotic nuclei judged by terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling (TUNEL). We conclude that, during cyclophosphamide
      accelerated diabetes, the predominant caspase-3 immunolabeling in intra- and
      extra-islet macrophages suggests that apoptosis of macrophages may be an
      important mechanism for their elimination. The virtual absence of caspase-3
      immunolabeling in most beta cells even during the height of beta cell loss
      supports the need for developing other markers of early beta cell apoptosis in
      the NOD mouse.

PMID- 14679059
TI  - Congenic mapping and candidate sequencing of susceptibility genes for Type 1
      diabetes in the NOD mouse.
AB  - Inheritance of type 1 diabetes is polygenic with a major susceptibility gene
      located in the major histocompatibility complex (MHC). In addition to MHC-linked
      susceptibility, a number of susceptibility genes have been mapped outside the MHC
      in both humans and animal models. In order to localize and identify
      susceptibility genes for type 1 diabetes, we have developed a series of congenic
      strains in which either susceptibility intervals from the NOD mouse, a mouse
      model of type 1 diabetes, were introgressed onto control background genes or
      protective intervals from control strains were introgressed onto NOD background
      genes. NOD. CTS-H-2 congenic mice, which possess recombinant MHC with NOD alleles
      at class II A and E genes, which are candidates for Idd1, revealed that Idd1
      consists of multiple components, one in class II (Idd1) and the other adjacent
      to, but distinct from, Idd1 (Idd16). Phenotypes of NOD. IIS-Idd3 congenic mice,
      which share the same alleles at both Il2 and Il21 as the NOD mouse, were
      indistinguishable from the NOD parental strain, indicating that both Il2 and Il21
      are candidates for Idd3. In contrast, NOD. IIS-Idd10 congenic mice, which share
      the same alleles at Fcgr1, a previous candidate for Idd10, as the NOD mouse, were
      protected from type 1 diabetes, suggesting that Fcgr1 may not be responsible for
      the Idd10 effect. These data suggest that the use of strain colony closely
      related to a disease model to find the same candidate mutation on different
      haplotypes and make congenic strains with this recombinant chromosome, termed
      ancestral haplotype congenic mapping, is an effective strategy for fine mapping
      and identification of genes responsible for complex traits.

PMID- 14679060
TI  - Establishing insulin 1 and insulin 2 knockout congenic strains on NOD genetic
      background.
AB  - As insulin is a major autoantigen in autoimmune diabetes and because the insulin
      gene region locus in humans has been linked to diabetes risk, we have bred
      insulin gene knockouts onto the NOD mouse. Mice differ from humans in terms that
      they express two nonallelic genes of insulin. Insulin 2 is the murine homologue
      of the human insulin gene and is located on mouse chromosome 7. Insulin 1 is
      thought to have evolved by a gene duplication event, lacks the second intron of
      the insulin 2 gene, and is located on mouse chromosome 19. The differential
      thymic expression of the insulin gene may be important for central tolerance
      induction. Here, we present the initial establishment of congenic knockouts and
      characterization of the congenic intervals corresponding to insulin 1 and insulin
      2 knockout genes on mouse chromosome 19 and 7, respectively.

PMID- 14679061
TI  - Relationship between beta cell mass of NOD donors and diabetes development of NOD
      scid recipients in adoptive transfer system.
AB  - BACKGROUND: There is controversy about the way the beta cell mass is reduced in
      type 1 diabetes. One view is that a gradual fall in beta cell mass begins soon
      after the onset of insulitis. Another view is that a sudden wave of beta cell
      destruction occurs just before the onset of diabetes. To clarify how the beta
      cell mass is reduced, we performed adoptive transfer experiments and examined the
      relationship between the pancreatic status of NOD donors and the time taken to
      transfer diabetes into NOD-scid recipients. METHODS: We killed 18-week-old female
      NOD mice (n = 20), removed their spleen, and transferred splenocytes into 5-week
      old female NOD-scid mice (n = 60). The relationship between the pancreatic status
      of donors and the time taken to transfer diabetes into recipients was assessed.
      As pancreatic status, we measured insulin content and severity of insulitis.
      RESULTS: There was no linear correlation between the pancreatic status of donors
      and the time taken to transfer diabetes into recipients. NOD donors who needed 7
      or more weeks to transfer diabetes in NOD-scid recipients had similar levels of
      insulin content or severity of insulitis as those of NOD donors who could not
      transfer diabetes. On the other hand, NOD donors who needed 6 or less weeks to
      transfer diabetes in recipients had similar levels of insulin content or severity
      of insulitis as those of diabetic NOD mice. CONCLUSIONS: According to our
      observations, beta cell mass seems to be preserved until just before the onset of
      diabetes and decreased dramatically within a few weeks.

PMID- 14679062
TI  - Hen egg white lysozyme vaccination induces acute shock in NOD mice.
AB  - To investigate whether vaccination could induce lethal shock and which mechanisms
      are involved in this phenomenon, we tested a panel of autoantigens or diabetes
      irrelevant peptides or proteins in nonobese diabetic (NOD), Balb/c, and C57Bl/6
      mice. Of the antigens tested, only nondiabetogenic hen egg white lysozyme induced
      a severe form of shock exclusively in NOD mice. The mechanism involved is
      suggestive of a Th(2)-mediated anaphylactic reaction possibly connected to
      activation of PAF and triggering of DIC.

PMID- 14679063
TI  - In vivo expression of B:9-23 peptide/I-A(g7) complex may abrogate the inhibition
      of diabetes induced by RGD-fiber-mutant adenovirus in NOD mice.
AB  - Insulin B chain peptide B:9-23 given to NOD mice decreases the development of
      diabetes, and phase II trials of an altered peptide ligand of B:9-23 are under
      way in humans. We have created a gene for the NOD MHC class II beta chain,
      covalently linked to the B:9-23 peptide. B lymphoma cells transfected with the
      gene stimulated NOD islet-derived B:9-23 reactive T cell clones in vitro. In this
      study, we generated an RGD-fiber-mutant adenovirus vector encoding the covalent
      B:9-23 peptide/I-A(g7) gene (Ad-RGD-B:9-23) to test whether in vivo expression of
      the gene could protect NOD mice from diabetes. NOD female mice were injected
      intramuscularly with 5 x 10(8) PFU of Ad-RGD-B:9-23 and empty RGD-adenovirus
      vector. A single administration of the empty vector did not alter the expression
      of insulin autoantibodies, but delayed the onset of diabetes in NOD mice. In
      contrast, Ad-RGD-B:9-23 immunization induced an early expression of insulin
      autoantibodies, but did not change the disease occurrence compared to control NOD
      mice. Our results suggest that adenovirus infection could confer protection from
      diabetes in NOD mice. The in vivo expression of covalent B:9-23 peptide/class II
      complex by adenovirus gene transfer might activate anti-insulin autoimmunity,
      resulting in abrogation of the inhibition of diabetes induced by an RGD-fiber
      mutant adenovirus vector.

PMID- 14679064
TI  - Abnormal peripheral blood dendritic cell populations in type 1 diabetes.
AB  - Type 1 diabetes (T1D) is a T cell-mediated disease. Various DC populations play
      important roles in initiating and directing T cell responses and thus may be
      critical for T1D pathogenesis. We thus examined peripheral blood DC1 and DC2
      populations by flow cytometry in healthy controls, subjects at risk for T1D, new
      onset patients, and established T1D patients. We found a significant increase in
      the number of DCs (including DC1 and DC2) in at-risk subjects and those with new
      onset T1D versus healthy controls and established T1D patients (ANOVA; p <
      0.0001). Analysis of DC1 and DC2 subsets in these same groups demonstrated a
      significant decrease in the ratio of DC1 and DC2 in subjects at risk and new
      onset and established T1D patients in contrast with healthy controls (p <
      0.0001). Both subsets of peripheral blood DCs from T1D patients expressed
      significantly higher levels of HLA-DR than healthy controls. Peripheral blood
      mononuclear cells from T1D patients secreted significantly higher amounts of IFN
      alpha than controls, and IFN-alpha production correlated inversely with the
      DC1/DC2 ratio. This study demonstrates a marked increase in peripheral blood DC
      numbers that occurs during a time of active autoimmunity in at-risk subjects and
      patients with new-onset T1D, but is lost in established diabetes. However, the
      abnormal distribution of peripheral blood DC populations appears to be a
      persistent phenotype in all stages of T1D.

PMID- 14679065
TI  - Characterization of dendritic cells in humans with type 1 diabetes.
AB  - The characterization of dendritic cells (DCs) in diabetes has primarily examined
      in vitro-generated DCs. In this study, we have compared the composition and
      phenotype of naturally occurring DCs within the peripheral blood of subjects with
      type 1 diabetes, latent-onset autoimmune diabetes in adults, and nondiabetic
      controls. We find that circulatory DC subsets exist in normal frequencies and
      phenotypic states in diabetic patients. In vivo, DCs were located around the
      pancreatic islets in type 1 diabetic patients, but were absent in pancreatic
      tissue of normal controls. These findings provide new insight toward
      understanding the pathological role of DCs in type 1 diabetes.

PMID- 14679066
TI  - NKT cell frequency in Japanese type 1 diabetes.
AB  - A numerical and functional deficit of natural killer T (NKT) cells has been
      reported to be associated with the pathogenesis of Caucasian patients with type 1
      diabetes. However, a conflicting finding of a higher frequency of NKT cells
      (Valpha24+ Vbeta11+ T cells) was observed in islet-associated Ab+ and Ab-
      Japanese "classic" type 1 diabetes. Here, we combined the data of NKT cell
      frequency in Ab+ and Ab- "classic" type 1 diabetic patients and then analyzed the
      relationship between NKT cell frequency and disease activity.

PMID- 14679067
TI  - IL-6 modulates hyperglycemia-induced changes of Na+ channel Beta-3 subunit
      expression by Schwann cells.
AB  - Our data show the suppressive effect of hyperglycemia on expression of voltage
      gated Na+ channel beta3 subunit by Schwann cells as well as the protection of
      beta3 expression by treatment with IL-6. Our findings have direct relevance for
      therapy of diabetic neuropathy.

PMID- 14679068
TI  - Glucose-responsive expression of the human insulin promoter in HepG2 human
      hepatoma cells.
AB  - The concept of insulin production afforded by hepatic gene therapy retains
      promise as a potential therapy for type 1 diabetes, but the approach has been
      limited by the need for strict transgene regulation in response to fluctuating
      levels of both glucose and insulin. Furthermore, while hepatocytes contain
      various glucose-responsive elements, they lack the appropriate regulated
      secretory system necessary for insulin release, thereby necessitating the
      requirement for transcriptional regulation of hepatic insulin production under
      the direction of a glucose-responsive promoter. To address this, we have
      evaluated several glucose-responsive promoters that may be used successfully for
      hepatic insulin production via recombinant adeno-associated virus (rAAV) therapy.
      Our results suggest that the human insulin promoter represents a strong candidate
      as a robust, glucose-responsive promoter for regulated hepatic insulin
      production.

PMID- 14679069
TI  - Interleukin-6 protects MIN6 beta cells from cytokine-induced apoptosis.
AB  - Host nonspecific beta cell injury by cytokines has been implicated in the process
      of early islet graft dysfunction. Islet transplant destruction by cytokines
      released from inflammatory cells that infiltrate the graft is thought to be
      mainly mediated by NF-kappaB-dependent nitric oxide (NO) production by the islet.
      In this study, we aimed to evaluate the role of IL-6 in making a beta cell
      resistant to cytokine-induced apoptosis by decreasing the NF-kappaB-dependent NO
      production and compared the result with that of the expression of a dominant
      negative inhibitor of NF-kappaB (DN NF-kappaB). Incubation of MIN6 cells with IL
      1beta, IFN-gamma, and TNF-alpha (cytomix) increased production of nitrites, with
      increased expression of iNOS mRNA. When treated with cytomix, the DN NF-kappaB
      transfected mutant demonstrated significantly less nitrite production and
      apoptosis than parent MIN6. NO production was effectively blocked by IL-6 as well
      as by N-monomethyl-l-arginine (l-NMMA). Inhibition of the NO production led to
      decreased rate of apoptosis accompanied by downregulation of the proapoptotic
      molecule Bax and increased expression of the antiapoptotic molecule Bcl-2 and Bcl
      x(L). These data indicate that cytokine-induced cell death in the MIN6 beta cell
      line involves mechanisms that are, in part, NF-kappaB- and NO-dependent.
      Inhibition of the NO production by the incubation of the MIN6 cells by the
      pretreatment of IL-6 or l-NMMA is cytoprotective and can be used as a substitute
      for the expression of DN NF-kappaB.

PMID- 14679070
TI  - A diabetes-related epitope of GAD65: a major diabetes-related conformational
      epitope on GAD65.
AB  - The 65-kDa isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen
      in type 1 diabetes, and most patients have serum antibodies reactive with
      conformational epitopes on the GAD65 molecule. The aims of this study were to
      prepare mutants of GAD65 to further localize the type 1 diabetes epitope in the
      region of the PEVKEK loop of GAD65 and to identify the particular amino acids
      within the epitope that are recognized by autoimmune diabetes sera.

PMID- 14679071
TI  - SOX13 autoantibodies are likely to be a supplementary marker for type 1 diabetes
      in Korea.
AB  - The SOX13, one of the family of transcription factors that play key roles in
      organ development, is reported to be a diabetes autoantigen, islet cell antigen
      12 (ICA12). Recently, a study of antibodies to SOX13 was conducted in patients
      with type 1 diabetes mellitus (T1DM) indicating that these antibodies potentially
      identified patients without antibodies to the major T1DM-associated autoantigens,
      insulin, GAD, or IA-2. We know that the prevalence of islet-specific
      autoantibodies (GAD, IA-2) in Korean patients is much lower than that in white
      patients. It may be possible that other autoantibodies that could be directed to
      as yet unknown antigen may play a role in Korean T1DM patients. To investigate
      this, we measured SOX13 autoantibodies applying a radioligand binding assay using
      in vitro transcribed and translated antigen in 188 T1DM patients (mean duration,
      4.2 years) and 64 T2DM patients and compared the results with those of 101
      healthy control subjects. SOX13 autoantibodies occurred at a significantly higher
      frequency among T1DM patients (55/188, 29.3%) than among T2DM patients (4/64,
      6.2%) or healthy adult controls (1/101, 1%). The 55 patients with positive SOX13
      antibodies had significantly shorter duration of diabetes than SOX13 antibody
      negative patients (3.6 +/- 2.8 vs. 4.5 +/- 3.9 years; p < 0.05). We could detect
      a prevalence similar to control in patients with Hashimoto's thyroiditis (4.9%, n
      = 101) and rheumatoid arthritis (6.7%, n = 89). As a whole, 44 of the 55 patients
      with SOX13 antibodies had at least one or more other autoantibodies to the major
      T1DM-associated autoantigens. However, SOX13 antibodies were the only antibodies
      detected as positive in 1 of the 11 new-onset patients. We conclude, therefore,
      that these antibodies are likely to be one of several epitope-spreading responses
      to islet- or nonislet-specific autoantigens seen in the development of T1DM, and
      they may be used as a supplementary marker for investigating T1DM in Korea.

PMID- 14679072
TI  - Development and validation of a radioligand binding assay to measure insulin
      specific IgG subclass antibodies in human serum.
AB  - The objective was to develop and validate a radioligand binding assay for insulin
      antibodies (IABs) of the IgG1, IgG2, IgG3, and IgG4 subclasses in human serum.
      The validation studies focused on determining specificity, capacity, linearity,
      sensitivity, and precision of each assay. It was seen that our assay for IAB IgG
      subclasses is specific and has sufficient capacity to measure each of the
      subclasses in human serum. Moreover, the linear region and limits of detection
      and quantitation for each assay are clearly determined.

PMID- 14679073
TI  - Development and validation of radioligand binding assays to measure total, IgA,
      IgE, IgG, and IgM insulin antibodies in human serum.
AB  - Radioligand binding assays for total and Ig classes of insulin antibodies (IAB)
      were developed and validated. For each assay, insulin-extracted serum samples
      were incubated with radiolabeled insulin in the presence and absence of high
      levels of unlabeled insulin to determine nonspecific binding and total binding,
      respectively. To measure total IAB, antibody-bound insulin was precipitated with
      a polyethylene glycol solution, washed, and counted in a gamma-counter. To
      measure IgG IAB, samples were treated with protein G-Sepharose beads,
      centrifuged, washed, and counted. For the measurement of IgA, IgE, and IgM IAB,
      IgG was removed from the samples and treated with anti-IgA, -IgE, or -IgM
      conjugated to Sepharose beads, centrifuged, washed, and counted. The
      acid/charcoal extraction of bound and unbound insulin from serum samples was
      optimized. Specificity and binding capacity of the protein G and antibody-bound
      beads were evaluated and optimized. The linear region of the total and IgG IAB
      assays was determined using serum samples containing high levels of insulin
      antibodies. The limit of quantitation, limit of detection, and precision for all
      the assays were also determined.

PMID- 14679074
TI  - Induction of diabetes-related autoantibodies below cutoff for "positivity" in
      young nondiabetic children.
AB  - The aim was to study the natural course of diabetes-related autoantibodies at low
      concentrations, below "positivity", in a nondiabetic population followed up from
      infancy. Blood samples were taken from 205 children at 6 weeks, 6 months, 18
      months, and 5 years of age. Autoantibodies against GAD(65) (GADA), tyrosine
      phosphatase (IA-2A), and insulin (IAA) were determined by radioligand-binding
      assays. All children had detectable levels of GADA and approximately half had IA
      2A, but only approximately 10% had detectable levels of IAA during the follow-up
      period. Many children developed IA-2A already at 6 months of age, similar
      concentrations were seen at 18 months, and then the levels of IA-2A decreased
      until 5 years of age. GADA were induced less often at 6 months of age, increased
      up to 18 months, and fluctuated at similar levels up to 5 years of age. IAA were
      detectable in so few children and at low levels, so no trend in natural course
      could be revealed. We conclude that there is a natural induction of humoral
      immune response to beta cell autoantigens early in life. Our results suggest that
      the mechanisms of beta cell tolerance to GAD and IA-2 differ in healthy children.

PMID- 14679075
TI  - Cow-milk-free diet during last trimester of pregnancy does not influence diabetes
      related autoantibodies in nondiabetic children.
AB  - The aim was to study whether cow-milk-free diet during the last trimester of
      pregnancy influences the development of diabetes-related autoantibodies in
      nondiabetic children. We also examined the effect of later introduction of cow
      milk proteins and gluten. Blood samples were taken from 205 children at 6 weeks,
      6 months, 18 months, and 5 years, whose mothers had been randomized to either a
      cow-milk-free diet or not during the last trimester of pregnancy. During the
      first 3 months of life, cow milk proteins were not fed to the children.
      Autoantibodies against GAD.(65) (GADA), tyrosine phosphatase (IA-2A), and insulin
      (IAA) were determined by a radioligand-binding assay. We found specific
      autoantibodies, although in low concentrations below the traditional cutoff for
      positivity in the children. The diet of the mother during pregnancy had no
      influence on development of autoantibodies, nor did duration of breast-feeding or
      time for introduction of gluten. Cow milk introduction between 3 and 6 months
      caused a transient increase in GADA at 6 months of age (p < 0.05). Children who
      developed atopic disease had significantly lower IA-2A at 6 months (p < 0.001).

PMID- 14679076
TI  - Difference in gene expression profiles between human CD4+CD25+ and CD4+CD25- T
      cells.
AB  - We studied the gene expression profiles of human CD4+CD25+ and CD4+CD25- T cells
      by using cDNA microarrays. Our preliminary results indicate that there are likely
      significant differences in the regulation of apoptosis, cell cycle, cytokine
      receptor, cell-cell interaction, and stress pathway genes between these two
      subtypes of T cells.

PMID- 14679077
TI  - The design of a gene chip for functional immunological studies on a high-quality
      control platform.
AB  - We have created an immunology-related microarray chip containing primarily known
      genes with well-studied functional properties. By looking at known genes rather
      than expressed sequence tags, we hope to gain a better understanding of
      immunological pathways and how they work. The immunology gene chip contains genes
      from the following functional categories: T cell genes; B cell genes; dendritic
      cell genes; chemokine and cytokine genes; apoptosis genes; cell cycle genes; cell
      interaction genes; general hematology and immunology genes; and adhesion genes.
      We have also developed a novel three-color cDNA array platform in which arrays
      are directly visualized before hybridization, which allows us to select only high
      quality chips for our experiments. In an effort to provide quantitative quality
      control for each array element as well as the entire chip, we have developed
      Matarray, a software package for image processing and data acquisition. With
      Matarray, we have built a quantitative data filtering and normalization scheme
      that has proved to be more efficient than the existing methods. The list of
      immunology chip genes is available from the authors.

PMID- 14679078
TI  - Relationship between T and B cell responses to proinsulin in human type 1
      diabetes.
AB  - In type 1 diabetes, humoral and cell-mediated responses to insulin and proinsulin
      are detectable. Autoantibodies to insulin are associated with impending disease
      in young individuals and are used as predictive markers to determine disease
      risk. The aim of this study was to investigate whether different cytokine
      patterns of cellular reactivity to insulin might serve as additional specific
      markers of disease maturation and might improve disease prediction in individuals
      at risk. We correlated T and B cell responses to insulin in subjects with
      increased genetic risk (HLA-DRB1*04, DQB1*0302) for diabetes with or without
      islet autoantibodies (Ab+ subjects and controls, respectively) and HLA-matched
      patients. Peripheral blood mononuclear cells were stimulated with 15 overlapping
      proinsulin peptides (16-mer), and proinflammatory Th1 (IFNgamma) and anti
      inflammatory Th2 (IL-4) cytokines were analyzed. We observed a simultaneous
      increase in IL-4 and IFNgamma secretion in early islet autoimmunity of Ab+
      subjects, but not in insulin-treated T1D patients. Furthermore, the increase in
      IL-4 secretion in Ab+ subjects was associated with insulin autoantibody
      responses. There was no correlation of either IFNgamma or IL-4 secretion with
      insulin antibody responses in patients already treated with exogenous insulin. In
      conclusion, our findings reveal that quantification of cytokine responses to
      proinsulin in peripheral blood may prove to be a promising specific marker of
      diabetes progression and could, in addition to insulin autoantibodies, be used in
      the prediction of type 1 diabetes.

PMID- 14679079
TI  - Inheritance of MHC class II genes in Lithuanian families with type 1 diabetes.
AB  - Type 1 diabetes mellitus (DM) is caused by genetic and environmental factors.
      Twice as many fathers as mothers of children with type 1 DM have the disease. The
      reason for the differences remains unclear. We looked at the transmission rates
      of diabetes-related alleles from parents to children with diabetes. All children
      with newly diagnosed type 1 DM from August 1, 1996 to August 1, 2000, aged 0 to
      15 years, in Lithuania were invited to participate. Blood samples for full
      genetic analysis were available from 125 families. HLA DQA1, DQB1, and DRB1
      typing was done on DNA extracted from peripheral blood, by polymerase chain
      reaction amplification, manual dot-blotting onto nylon membranes, synthetic
      sequence-specific oligonucleotide probe 3'-end labeling with (32)P-dCTP, and
      hybridization, followed by stringency washes, autoradiography, and allele
      calling. Frequency of diabetes risk-related alleles DQB1*0302, DQA1*0201, DR4,
      and DR3 was less prevalent among Lithuanian than among Swedish children with type
      1 DM. Transmission rates of DR4-DQB1*0302-DQA1*0301 and DR3-DQB1*0201-DQA1*0501
      haplotypes from parents were higher than expected: chi(2) (TDT) 30.56, p <
      0.0001, and chi(2) (TDT) 11.26, p = 0.0008, respectively. DQB1*0302 and DR4 were
      significantly more frequently transmitted from both parents, but DR3 was
      transmitted more frequently only from mothers. Any of these alleles had similar
      frequencies among female and male offspring. We conclude that, besides DR4
      DQB1*0302-DQA1*0301 and DR3-DQB1*0201-DQA1*0501, there are other inherited
      alleles that determine risk for type 1 DM among children in Lithuania. Fathers
      might transfer other alleles of disease susceptibility in higher frequency or
      mothers might provide a protective environment during pregnancy, which results in
      higher risk to offspring of fathers than mothers to develop diabetes.

PMID- 14679080
TI  - Ethnic differences in the associations between the HLA-DRB1*04 subtypes and type
      1 diabetes.
AB  - The HLA genotype DRB1*03,DQB1*0201/DRB1*04,DQB1*0302 confers a 25-fold increase
      in the risk of type 1 diabetes. In persons with this genotype, DRB1*0405, *0402,
      and *0401 subtypes have been reported to further increase risk, whereas the *0403
      and *0406 alleles confer a relative protection. We compared the frequencies of
      the DRB1*04 alleles in 193 type 1 diabetic patients with the HLA
      DRB1*03,DQB1*0201/DRB1*04,DQB1*0302 genotype (140 non-Hispanic white [NHW] and 53
      Hispanic) and 205 nondiabetic controls (142 NHW and 63 Hispanic). In addition, 87
      NHW first-degree relatives of type 1 diabetes patients were studied: 33 positive
      and 54 negative for autoantibodies to insulin, GAD65, or IA-2. The HLA-DRB1 was
      typed using standard PCR SSOP methods. DRB1*0401 (OR, 2.19; 95% CI, 1.36-3.54) in
      NHW and *0405 (OR, 3.78; 95% CI, 1.43-10.0) in Hispanics were significantly
      associated with T1DM, whereas DRB1*0403 was protective (OR, 0.19; 95% CI, 0.04
      0.89 in NHWs; OR, 0.10; 95% CI, 0.01-0.83 in Hispanics). Associations between the
      DRB1*04 alleles and prediabetic islet autoimmunity were generally in the same
      direction as those with diabetes. Among diabetic patients, the mean age of
      diagnosis appeared to be higher among those with the *0403 and *0407 allele
      compared with the others. In summary, on the DRB1*03,DQB1*0201/DRB1*04,DQB1*0302
      genotypes, the *0403 allele confers relative protection from type 1 diabetes and
      development of islet autoantibodies in both Hispanics and NHWs and is associated
      with older age at diabetes diagnosis. Although the associations between diabetes
      and *0401 and *0405 appear to differ somewhat between Hispanics and NHWs, overall
      there is no significant difference between these two ethnic groups.

PMID- 14679081
TI  - MIC-A genotypes 4/5.1 and 9/9 are positively associated with type 1 diabetes
      mellitus in Brazilian population.
AB  - The aim of our study was to evaluate the frequencies of MIC-A alleles and
      genotypes in Brazilian patients with type 1 diabetes mellitus (T1DM) and healthy
      controls. MHC class I chain-related gene-A (MIC-A) has been shown to be
      associated with susceptibility to T1DM in different populations. We analyzed the
      DNA samples from 86 patients and 201 healthy controls for MIC-A by PCR
      amplification, and fragment sizes were determined in an ABI prism DNA sequencer.
      We found increased frequencies of two genotypes, MIC-A 4/5.1 (pc = 0.006; OR,
      6.1) and 9/9 (pc = 0.045; OR, 5.75), in our patients (mean diagnosis age, 11.70
      years; SD, 8.86; mean age, 20.44 years; SD, 12.17) compared with the controls
      (median age, 26.41 years; SD, 8.87).

PMID- 14679082
TI  - HLA-DRB1 and MICA in autoimmunity: common associated alleles in autoimmune
      disorders.
AB  - Autoimmune disorders such as type 1 diabetes (T1DM), celiac disease (CD), and
      Addison's disease (ADD) develop in individuals with genetic susceptibility that
      are exposed to environmental triggering factors not completely defined. Patients
      with an autoimmune disease (and their relatives) are at increased risk of
      developing another disorder, and this might be caused by a common genetic origin
      of autoimmunity; for example, HLA class II region in 6p21 shows a very strong
      association with most diseases. The aim of this study was to determine whether
      shared susceptibility markers extend from the central (DRB1) through the
      telomeric (MICA) HLA region. We analyzed three independent sets of families with
      one autoimmune disease, T1DM, CD, or ADD, and genotyped them for HLA-DRB1 and for
      the exon 5 GCT polymorphism of MICA. For HLA-DRB1, allele DRB1*0301 was the only
      one associated with risk for all three diseases; in the case of MICA, allele A9
      was found to be the common protective allele. Haplotype analysis shows that
      haplotype A5.1-DRB1*0301 confers risk to autoimmunity. Our results show that
      there are common risk and protection alleles in both loci, suggesting a core of
      genetic association with autoimmunity (HLA-DRB1*0301 risk; A9 protection) that
      could be modulated by other alleles/loci or environmental factors toward one or
      another disease. Some alleles are part of conserved haplotypes (A5.1-DR3, A5.1
      DR2), whereas others seem to have independent effect (A9) and support the idea of
      two independent loci in this region.

PMID- 14679083
TI  - 5'-Insulin gene VNTR polymorphism is specific for type 1 diabetes: no association
      with celiac or Addison's disease.
AB  - The VNTR region located at the 5'-end of the insulin gene on chromosome 11p15.5
      is linked to susceptibility to type 1 diabetes mellitus (T1DM), and class I
      alleles have been associated with increased risk of disease, whereas class III
      alleles are considered to be protective. Although a potential effect on the
      expression level of thymic insulin and a consequent abnormal tolerance have been
      proposed as an explanation, it is still not clear whether the association is
      specific for T1DM or whether it is shared by other autoimmune disorders. To
      investigate the contribution of INS-VNTR to the genetic susceptibility to
      autoimmune disorders, we analyzed 102 autoantibody-positive T1DM patients, 59
      patients with celiac disease (CD), and 57 patients with Addison's disease (ADD),
      as well as 111 unrelated healthy individuals from the general population. When
      analyzing the results, class I allele frequencies were 85.8% in the T1DM group,
      77% among CD patients, 71% in the ADD group, and 76.1% in the general population.
      Association with increased risk was seen only in the T1DM group (pc = 0.015).
      Risk to T1DM was associated with the class I/class I homozygous genotype (RR,
      1.92; 95% CI, 1.03-3.6). In conclusion, INS-VNTR does not seem to be involved in
      the susceptibility to autoimmune diseases other than T1DM and can be considered a
      diabetes-specific locus.

PMID- 14679084
TI  - Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) P22 Phox
      C242T gene polymorphism in type 1 diabetes.
AB  - Type 1 diabetes is caused by the immune-mediated destruction of insulin-secreting
      pancreatic beta cells and is thought to be an autoimmune disease resulting from a
      complex interaction of genetic and environmental factors. In animal models of
      type 1 diabetes, macrophages and their products, superoxides, have central roles
      in the beta cell destruction, but in humans their roles remain unclear.
      Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase produces superoxide
      in macrophages, and its essential component, p22 phox, is a critical enzyme for
      superoxide production. The C242T polymorphism in the p22 phox coding gene has
      been reported to be associated with reduced oxidase activity. We therefore
      investigated whether the p22 phox gene polymorphism affected the susceptibility
      to and clinical course of type 1 diabetes. We examined 287 Japanese type 1
      diabetic patients and 425 unrelated nondiabetic subjects. In addition, we
      allocated the diabetic patients to the following three groups: (1) acute-onset
      type 1 diabetes with at least one autoantibody (GADA, IA-2, IAA); (2) acute-onset
      type 1 diabetes without autoantibodies; and (3) slow-onset type 1 diabetes with
      autoantibody. We could not find a significant difference in p22 phox genotype and
      T allele frequency between overall type 1 diabetic patients and control subjects.
      Regardless of the onset pattern and autoantibody positivity of type 1 diabetes,
      no difference in p22 phox genotype and T allele frequency was found among the
      groups. In conclusion, the p22 phox C242T gene polymorphism did not affect the
      susceptibility to and clinical course of Japanese type 1 diabetes.

PMID- 14679085
TI  - Stromal cell-derived factor-1 chemokine gene polymorphism is not associated with
      onset age of Japanese type 1 diabetes.
AB  - Type 1 diabetes is characterized by cell-mediated autoimmune destruction of
      pancreatic beta cells. Although the disease shows a strong association with HLA
      class II alleles, other genes may influence the initiation or the rate of
      progression of the autoimmune process. Recently, it was reported that a
      polymorphism of the stromal cell-derived factor-1 (SDF-1) (a kind of chemokine)
      gene was associated with early onset of type 1 diabetes in Caucasians. Therefore,
      we examined SDF-1 gene polymorphism in Japanese type 1 diabetes in this study. We
      examined the SDF-1 gene polymorphism (801G-->A) in 298 unrelated Japanese type 1
      diabetic patients and 270 healthy subjects by the TaqMan PCR method. Allelic and
      genotypic frequencies of the SDF-1 A variants were similar in overall type 1
      diabetic patients and healthy subjects. We then stratified the patients by their
      onset pattern (acute vs. slow onset) and islet-associated autoantibody
      positivity. However, no significant difference was found among each group of type
      1 diabetes. Furthermore, unlike the previous report in "Caucasian" type 1
      diabetics, the SDF-1 A variant was not associated with early onset of the disease
      in Japanese type 1 diabetics. The SDF-1 gene polymorphism was not associated with
      onset age (or onset pattern) of type 1 diabetes in Japanese. Further study is
      necessary to conclude whether SDF-1 gene polymorphism affects the onset age in
      type 1 diabetes in general.

PMID- 14679086
TI  - Mutation scan of a type 1 diabetes candidate gene: the human interleukin-18
      binding protein gene.
AB  - Type 1 (insulin-dependent) diabetes, T1DM, is the result of an immune-mediated
      destruction of the pancreatic beta cells dependent mainly on T helper cells and
      macrophages. Interleukin-18 (IL-18) is a proinflammatory cytokine produced mainly
      by macrophages. IL-18 is capable of inducing T lymphocyte synthesis of IFNgamma,
      thereby skewing the T helper response toward a T helper type 1 (Th1) profile. IL
      18 binding protein (IL18BP) neutralizes IL-18 and leads to a reduced Th1
      response. Polymorphisms in IL18BP may affect the activity of IL-18 and the
      magnitude of the Th1 response and may play a role in the pathogenesis of T1DM.
      The aim of the study was therefore to identify polymorphisms in IL18BP and to
      test these for association with T1DM. We evaluated the human IL18BP gene on
      chromosome 11q13 as a candidate susceptibility gene for T1DM and scanned the
      entire IL18BP (promoter, exons 1-6, and 3'UTR) for polymorphisms using single
      strand conformational polymorphism analysis and direct sequencing. We identified
      a total of 11 polymorphisms, all having allele frequencies ranging between 0.05
      and 0.10. Four were in the 5'UTR: -257G-->T, -78C-->T, -65G-->A, and -59A-->G.
      Three were in intron 3: IVS3+140A-->C, IVS4-147G-->T, and IVS4-59G-->T. The last
      four, 38*A-->T, 48*T-->A, 388*C-->G, and 440*_441*insG, were in the 3'UTR of
      IL18BP. However, none of these were frequent enough to permit association studies
      in T1DM and we conclude that IL18BP does not contribute to the overall genetic
      susceptibility to type 1 diabetes.

PMID- 14679087
TI  - Caspase 7 is a positional candidate gene for IDDM 17 in a Bedouin Arab family.
AB  - The IDDM 17 locus was mapped to an 8-cM interval at chromosome 10q25.1 based on
      linkage in a large Bedouin Arab family with 19 affected relatives. Caspase 7
      (CASP7), an apoptosis-related cysteine protease, is one of the few known genes in
      this region. CASP7 is involved in the activation cascade of caspases responsible
      for apoptosis execution. Only 1 of the 18 SNPs in CASP7 (SNP144692) differed
      significantly in frequency in the haplotypes found in affected individuals
      compared to control Bedouin haplotypes. This same SNP showed evidence of
      association with diabetes in a subset of patients (DR3/DR4*0302) from HBDI
      families.

PMID- 14679088
TI  - Interleukin-10 gene promoter region polymorphisms in patients with type 1
      diabetes and autoimmune thyroid disease.
AB  - Type 1 diabetes is a heterogeneous autoimmune disease and is frequently
      associated with other organ-specific autoimmune diseases, including autoimmune
      thyroid disease (AITD). Type 1 diabetic patients with AITD are known to show
      distinct clinical and immunological features from patients without AITD. This
      study investigated whether interleukin-10 (IL-10) gene promoter region
      polymorphisms are associated with susceptibility to type 1 diabetes and AITD. The
      frequency of -1082G/A, -819C/T, and -592C/A polymorphisms was analyzed in 54 type
      1 diabetic patients with AITD, 74 type 1 diabetic patients without AITD, 124
      nondiabetic patients with AITD, and 107 healthy subjects in a case-control study.
      No significant differences on the allele and genotype frequencies of three
      polymorphisms were found not only in type 1 diabetic patients with AITD compared
      with normal controls, but also between nondiabetic patients with AITD and healthy
      controls. The distribution of IL-10 gene haplotypes was also similar between both
      patient groups and normal controls. These results suggest that IL-10 gene
      promoter region polymorphisms are not associated with genetic susceptibility to
      type 1 diabetes and AITD.

PMID- 14679089
TI  - Single nucleotide polymorphism study of IDDM 17 in a Bedouin Arab family.
AB  - Type 1 diabetes is an autoimmune disease caused by a combination of genetic and
      environmental factors. On the basis of a genomic search for linkage in a Bedouin
      Arab family with 19 members with type 1 diabetes, we previously mapped the IDDM
      17 locus to the chromosome 10q25.1 region. The result from a recent genome scan
      showed suggestive evidence of linkage of IDDM 17 in a subset of Caucasian
      families in which all affected individuals have DR3, indicating that the IDDM 17
      locus might have a measurable effect in Caucasian populations from the United
      Kingdom and the United States. High-resolution SNP typing provides strong
      evidence of linkage disequilibrium to the IDDM 17 locus.

PMID- 14679090
TI  - No evidence for linkage in Swedish multiplex T1DM families to IL12B on chromosome
      5q33-34.
AB  - Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which the beta cells
      in the pancreas are destroyed by the body's own immune system. IL12 plays a role
      in pathological situations, such as septic shock, tissue damage during
      inflammation, and organ-specific autoimmune diseases. In NOD mice, administration
      of IL12 induces T1DM and administration of IL12 antagonists prevents T1DM.
      Linkage and association of IL12 to T1DM have been reported previously. We are
      unable to replicate this linkage on chromosome 5q33-34 in 184 Swedish families.
      Further, we exclude a gene with lambda(s) > 1.4 from this region. Together with
      previously published findings, these data make IL12 an unlikely major
      susceptibility gene for T1DM.

PMID- 14679091
TI  - Frequency of latent autoimmune diabetes in adults in Asian patients diagnosed as
      type 2 diabetes in Birmingham, United Kingdom.
AB  - The aims of our study were to measure autoantibodies to glutamic acid
      decarboxylase and autoantibodies to protein tyrosine phosphatase in patients with
      type 2 diabetes mellitus, patients with impaired glucose tolerance, and healthy
      controls of Asian origin from Birmingham, United Kingdom. According to our
      findings, 27% (9/33) of patients initially diagnosed with type 2 diabetes
      mellitus carry autoantibodies to GAD65.

PMID- 14679092
TI  - Two cases of "fulminant" type 1 diabetes suggesting involvement of autoimmunity.
AB  - Recently, a novel subtype of type 1 diabetes, so-called fulminant type 1
      diabetes, has been proposed. One of the characteristics of this subtype is the
      absence of detectable "islet-associated" autoantibody, so it was originally
      proposed as being "nonautoimmune-mediated"; however, it has not yet been
      concluded whether autoimmunity is involved. We have previously shown that serum
      interferon-inducible protein-10 and glutamic acid decarboxylase-reactive CD4(+)
      interferon-gamma-producing cells in the peripheral blood are good markers for T
      cell-mediated autoimmunity in type 1 diabetes. Here, we report two cases of
      fulminant type 1 diabetes in which these markers were detected and in which the
      involvement of islet-associated autoimmunity is suggested.

PMID- 14679093
TI  - Multicenter prevention trial of slowly progressive type 1 diabetes with small
      dose of insulin (the Tokyo study): preliminary report.
AB  - In 1996, we designed a randomized multicenter study to assess the effects of
      small doses of insulin on beta cell failure in slowly progressive type 1 diabetes
      (the Tokyo Study). We report here the preliminary results of this study. Glutamic
      acid decarboxylase 65 antibody (GADA)-positive patients were randomly divided
      into 2 groups: one group received insulin (Ins group), the other a sulfonylurea
      (SU group). Fifty-four patients (24 Ins group, 30 SU group) were analyzed at the
      end of a 4-year period. All patients underwent a 75 g oral-glucose test (O-GTT)
      every 6-12 months. The insulin-dependent stage was defined based on an integrated
      value of serum C-peptide levels on O-GTT ( summation operator CPR; sum of CPR at
      0, 30, 60, 90, and 120 min) below 4.0 ng/mL. The summation operator CPR in the SU
      group decreased progressively from 22.0 +/- 10.6 to 11.3 +/- 7.5 ng/mL over the
      48-month period (p < 0.001 vs. baseline). The summation operator CPR in the Ins
      group was unchanged. Among the SU group, 30% of subjects (9/30) progressed to
      IDDM, while 8.3% of Ins group subjects (2/24) progressed to IDDM (p = 0.087).
      With regard to the subjects who had a preserved C-peptide response ( summation
      operator CPR >/= 10 ng/mL), the proportion of SU group subjects who progressed to
      IDDM was significantly higher than that of the Ins group (7/28, 25% vs. 0/21, 0%,
      p = 0.015). Among subjects with a high GADA titer (>/=0 U/mL), 9/14 (64.3%) of
      the SU group, but only 2/16 (12.5%) of the Ins group, developed IDDM (p =
      0.0068). As to those with a high GADA titer and a preserved C-peptide response,
      SU group subjects progressed to IDDM (7/12, 58.3%) more frequently than Ins group
      subjects (0/14, 0%) (p = 0.0012). In summary, our results suggest that small
      doses of insulin effectively prevent beta cell failure in slowly progressive type
      1 diabetes. We recommend avoiding SU treatment and instead administering insulin
      to NIDDM patients with high GADA titer.

PMID- 14679094
TI  - Late-onset autoimmune diabetes in relatives of people with type 1 diabetes.
AB  - The Melbourne Prediabetes Family Study, a prospective study of first-degree
      relatives of people with type 1 diabetes (T1D), provided an opportunity to
      examine late-onset autoimmune diabetes within the context of a family history of
      T1D. We compared genetic, immunologic, and clinical features in relatives of
      people with T1D, who developed early- versus late-onset diabetes.

PMID- 14679095
TI  - Insulin resistance in latent autoimmune diabetes of adulthood.
AB  - Insulin resistance in patients with latent autoimmune diabetes of adulthood
      (LADA) was determined by homeostasis model assessment (HOMA). LADA was identified
      by a clinical phenotype of type 2 diabetes with antibodies to GAD65 and/or IA
      2/ICA512. All patients were managed with insulin therapy. Insulin resistance in
      LADA was lower than in antibody-negative type 2 diabetes, higher than in normal
      humans and in recent-onset type 1 diabetes, and similar to that in long-term type
      1 diabetes. Mean values for HOMA varied linearly with mean values for BMI, which
      accounted for much of the insulin resistance in these forms of diabetes. LADA
      resembles long-term type 1 diabetes with respect to insulin resistance and BMI,
      but occurs at an older age.

PMID- 14679096
TI  - Detection of GAD-reactive CD4+ cells in so-called "type 1B" diabetes.
AB  - OBJECTIVE: Although the majority of type 1 diabetes is considered to be type 1A,
      some patients with type 1 diabetes have no islet-associated autoantibody in their
      serum. This type of type 1 diabetes has usually been diagnosed as type 1B on the
      basis of islet-associated autoantibody-negativity. In this study, we tried to
      demonstrate the existence of islet-associated antigen-specific T cells in type 1
      diabetes without islet-associated autoantibody. RESEARCH DESIGN AND METHODS:
      Peripheral blood samples were obtained from 110 Japanese diabetic patients,
      including 15 type 2 diabetic patients. Measurement of islet-associated antigen
      specific cytokine response was performed by intracellular cytokine staining for
      flow cytometry. RESULTS: The number of GAD-reactive IFN-gamma-producing CD4+
      cells in 50,000 CD4+ cells in diabetics with type 1B (113.6 +/- 34.6, median 45),
      type 1A (132.4 +/- 33.3, median 25), and LADA (154.4 +/- 44.1, median 20) was
      higher than that in type 2 diabetics (0.3 +/- 0.3, median 0) and control subjects
      (3.8 +/- 2.4, median 0). When the normal upper limit of the number of GAD
      reactive CD4+ cells was set at the mean + 3SD of values in control subjects, at
      least half (52.4%) of the so-called "type 1B" patients were positive for GAD
      reactive IFN-gamma-producing CD4+ cells, a significantly larger proportion than
      that in type 2 diabetics (0%; p < 0.001). CONCLUSIONS: Assessment of T cell
      reactivity against islet-associated antigen may contribute to the diagnosis of
      "autoimmune-related" type 1 diabetes.

PMID- 14679097
TI  - Autoantibodies to GAD65 and IA-2 antibodies are increased, but not tissue
      transglutaminase (TTG-Ab) in type 2 diabetes mellitus (T2DM) patients from South
      India.
AB  - The frequency of autoantibody-positve T2DM patients identified as LADA was shown
      to be high in T2DM patients from Eastern India. In this study, we measured
      autoantibodies to GAD65, IA-2, and TTG in T2DM patients from Southern India. Our
      results show that either GAD65 or IA-2 was present in 30% of T2DM patients (n =
      155) and in 3% of controls for GAD65 and 1% of controls for IA-2 (n = 105). TTG
      Ab was not increased in T2DM patients compared to controls. Our results suggest
      that LADA is more frequent in Southern Indians than in European Caucasians, but
      not as high as in Eastern Indians.

PMID- 14679098
TI  - IA-2 autoantibodies are predominant in latent autoimmune diabetes in adults
      patients from eastern India.
AB  - Autoimmune diabetes or latent autoimmune diabetes in adults (LADA) among the
      clinically diagnosed type 2 diabetes patients from Cuttack in Eastern India was
      studied. GAD65 and IA-2 autoantibodies were measured by radioligand binding assay
      using recombinant human GAD65 and IA-2. The frequency of GAD65 was not
      significantly different between patients and controls. However, IA-2 antibodies
      were predominant in LADA patients and there were two distinct peaks, one in the
      age group of 20 to 30 years and another in the age group of 50 to 60 years. The
      data suggest that LADA is more frequent in Eastern Indian T2DM patients and the
      IA-2 is the predominant autoantibody in this population.

PMID- 14679099
TI  - Parents want to know if their child is at high risk of getting diabetes.
AB  - Not least among professionals, voices have been raised against screening research
      projects, which have been regarded as involving a risk of being unethical as they
      may disturb, scare, or even harm the included people without giving enough
      benefit. This problem with large-scale screening should be especially pronounced
      if increased risk of a serious disease like type 1 diabetes is identified when no
      effective prevention is available, and even more problematic if children were
      involved. ABIS (All Babies in Southeast Sweden) is a screening project including
      17,000 newborn babies in the general population, followed prospectively to
      identify children at risk to get diabetes, and to study the influence of
      environmental factors causing the disease process. Four hundred randomly selected
      ABIS families received a questionnaire on attitudes and ethical questions
      regarding the project to be answered anonymously: 293/400 (73.3%) answered;
      279/293 (95.3%) stated that they regarded it their right to be informed of
      results in the study and 278/293 (94.9%) said they really want to know. In fact,
      254/293 (86.7%) report wanting to know if their child has increased risk of
      getting diabetes even if there is no preventive measure available. This clear
      result supports the view that this type of study may well be ethically justified
      as long as informed consent can be given based on adequate understanding and
      voluntariness. The results may have implications for the design of future
      screening studies.

PMID- 14679100
TI  - Population-wide infant screening for HLA-based type 1 diabetes risk via dried
      blood spots from the public health infrastructure.
AB  - The frequency of type 1 diabetes mellitus (T1DM)-associated HLA DQ alleles in the
      U.S. Pacific Northwest is as high as in Scandinavia, which has the highest T1DM
      incidence in the world. The high regional rate of islet autoimmunity observed
      among DPT-1 relatives supports this notion. Fortunately, Washington State
      archives dried blood spots after legislature-mandated newborn screening. The
      Diabetes Evaluation in Washington (DEW-IT) study aims to show that population
      based prospective prediction of T1DM by HLA genotype screening followed by
      autoantibody surveillance can be performed within the public health
      infrastructure.

PMID- 14679101
TI  - Vaccinations may induce diabetes-related autoantibodies in one-year-old children.
AB  - Vaccinations have been discussed as one among many environmental candidates
      contributing to the immune process that later may lead to type 1 diabetes. ABIS
      (All Babies in Southeast Sweden) is a prospective cohort study following a
      nonselected birth cohort of general population. In a randomly selected sample
      collection from 4400 children, GADA and IA-2A have been determined at the age of
      1 year. The information on vaccinations was collected from questionnaires
      answered by the parents and was related to beta cell autoantibodies. When
      studying the induction of autoantibodies using the autoantibody level of 90th
      percentile as cutoff level, hemophilus influenza B (HIB) vaccination appeared to
      be a risk factor for IA-2A [OR 5.9 (CI 1.4-24.4; p = 0.01)] and for GADA [OR 3.4
      (CI 1.1-10.8; p = 0.04)] in logistic regression analyses. Furthermore, the titers
      of IA-2A were significantly higher (p < 0.01 in Mann-Whitney test) in those
      children who had got HIB vaccination. When 99th percentile was used as cutoff to
      identify the children at risk of type 1 diabetes, BCG vaccination was associated
      with increased prevalence of IA-2A (p < 0.01). We conclude that HIB vaccination
      may have an unspecific stimulatory polyclonal effect increasing the production of
      GADA and IA-2A. This might be of importance under circumstances when the beta
      cell-related immune response is activated by other mechanisms.

PMID- 14679102
TI  - Inhibition of STAT4 activation by lisofylline is associated with the protection
      of autoimmune diabetes.
AB  - We investigated the signal transduction pathway of IL-12 and showed that
      lisofylline (LSF) inhibited the signal transducer and activator of transcription
      factor-4 (STAT4) activation. Interruption of IL-12-mediated STAT4 activation
      prevented autoimmune diabetes in NOD mice.

PMID- 14679103
TI  - Reduced thymic expression of islet antigen contributes to loss of self-tolerance.
AB  - Type 1 diabetes (T1DM) results from a failure of central and peripheral tolerance
      to islet cell antigens. ICA69 belongs to a group of molecules expressed
      predominantly in neuroendocrine tissues (including pancreatic islets), which are
      targets of autoimmune responses in T1DM. These molecules are also expressed in
      the thymus and peripheral lymphoid organs by dendritic cells. The aim of the
      present study was to evaluate possible variation in thymic ICA69 expression,
      comparing diabetes-resistant controls to T1DM-prone NOD mice. Thymic tissue was
      retrieved from 3- to 6-week-old female B6, NOD-H2(b), and NOD mice. Paraffin
      embedded sections were stained with an ICA69-specific antibody in an
      immunoperoxidase assay. ICA69 staining of thymic sections from B6 and NOD.H2(b)
      showed strong and continual staining, yet the sections from the NOD mice showed
      significantly reduced staining for ICA69. Corroboration of the reduced level of
      ICA69 in the thymus of NOD mice has been obtained via analysis for the expression
      of ICA69 versus other candidate autoantigens (glutamic acid decarboxylase 65,
      glutamic acid decarboxylase 67, and insulin 2) in the thymus. Real-time PCR
      analysis, using cDNA generated from the thymus, displayed that the expression of
      GAD65, GAD67, and INS2 were equivalent when comparing NOD at any age to B6,
      BALB/cJ, and ALR/LtJ. In marked contrast, the level of ICA69 in the thymus of the
      NOD mice examined was significantly reduced when compared to the controls. In
      fact, the real-time PCR analysis strongly suggested that ICA69 was not expressed
      in the thymus of NOD mice. These findings support the hypothesis that the level
      of thymic ICA69 expression may be of importance in regulating self-tolerance in
      T1DM.

PMID- 14679104
TI  - Dietary microbial toxins and type 1 diabetes.
AB  - Toxins may promote type 1 diabetes by modifying or damaging the beta cell causing
      release of autoantigens. Streptomyces is a common soil bacterium that produces
      many toxic compounds. Some Streptomyces can infect vegetables, raising the
      possibility of dietary exposure to toxins. We aimed to identify toxins that erode
      cellular proton gradients in extracts of Streptomyces and infested vegetables and
      to establish the effect of low doses of these toxins on pancreatic islets in
      mice. The vacuolar ATPase inhibitors, bafilomycin and concanamycin, and the
      ionophore, nigericin, were identified in extracts from 4 of 13 Streptomyces
      isolated from infested potatoes and in potatoes themselves. Injection of
      bafilomycin A1 into mice impaired glucose tolerance, reduced islet size, and
      decreased relative beta cell mass. Thus, exposure to small quantities of
      bafilomycin in the diet may contribute to the cause of type 1 diabetes.

PMID- 14679105
TI  - Prevention of autoimmune diabetes through immunostimulation with Q fever
      complement-fixing antigen.
AB  - The most promising strategies for prevention of type 1 diabetes seem to be in the
      categories of immunomodulation (e.g., nondepleting anti-CD3, Diapep, linomide)
      and/or immunostimulation (e.g., QFA, BCG). We are currently undertaking a
      research program directed toward better understanding of immunostimulants to help
      maximize the likelihood of success of future human clinical trials for diabetes
      prevention. This program is focused on the key areas of optimization of vaccine
      dose and route of administration, development of surrogate immune markers, and
      elucidation of the mechanism of protection. The mechanism whereby QFA protects
      against diabetes currently is not known. The elucidation of the mechanism should
      help identify the optimal way in which to administer QFA to provide diabetes
      protection. It may also assist the development of even more potent
      immunostimulatory vaccines.

PMID- 14679106
TI  - AIRE-1 (autoimmune regulator type 1) as a regulator of the thymic induction of
      negative selection.
AB  - The monogenic autoimmune syndrome, APS-1 (autoimmune polyglandular syndrome type
      1), is characterized by the loss of self-tolerance to multiple organs. Although
      mutations in the AIRE (autoimmune regulator) gene are responsible for the APS-1,
      the function of AIRE is not known. AIRE may determine thymic induction of
      tolerance to self-antigens in multiple organs. To study the function of AIRE in
      induction of self-tolerance, an in vitro negative selection system was made using
      10(6) DO11.10 TCR transgenic thymocytes, 10(5) antigen-presenting cells (APC),
      and the different constructs of ovalbumin (OVA). In this system, the addition of
      the immunodominant epitopes of OVA peptide, the antigenic ligand for the DO11.10,
      made the thymocytes apoptotic and negatively selected. Overexpression of the AIRE
      gene in APC using retroviral transduction did not cause more thymocytes to become
      apoptotic. However, the suppression of the expression of AIRE in APC using the
      dominant-negative gene made the recovery rates of the thymocytes higher than
      those with the expression of LacZ as a control, and consequently inducing loss of
      self-tolerance. From these studies, it might be possible to suggest that the AIRE
      gene might regulate thymic induction of the negative selection process. The
      target genes for transcriptional regulation by AIRE have been investigated to
      study the influence of AIRE expression on other proteins in antigen presentation.
      The expression level of B7.1 was higher in APC expressing the dominant-negative
      form of AIRE. The target gene regulated by AIRE in transcription will be screened
      using cDNA microarray.

PMID- 14679107
TI  - Association of interleukin-18 gene promoter polymorphisms in type 1 diabetes and
      autoimmune thyroid disease.
AB  - Type 1 diabetes is a heterogeneous autoimmune disease and is often associated
      with other organ-specific autoimmune diseases, including autoimmune thyroid
      disease (AITD). IL-18 is a potent proinflammatory cytokine capable of inducing
      IFN-gamma production that is associated with the development of type 1 diabetes
      and AITD. The gene for IL-18 is located near Idd2 and has been reported to be
      associated with a susceptibility to type 1 diabetes. To test the putative
      involvement of IL-18 gene polymorphism in predisposition to type 1 diabetes and
      AITD, we conducted a case-control study in Japanese population. The SNPs at
      position -607 (C/A) and -137 (G/C) in the promoter region of the IL-18 gene were
      analyzed by sequence-specific PCR in 74 nondiabetic patients with AITD, 47 type 1
      diabetic patients with AITD, and 114 normal controls. There was no significant
      increase in the genotype and allele frequencies not only in nondiabetic patients
      with AITD compared with normal controls, but also in type 1 diabetic patients
      with AITD compared with normal controls. The distribution of IL-18 gene
      haplotypes was also similar between both patient groups and normal controls.
      These results suggest that polymorphisms of the IL-18 gene are not associated
      with a susceptibility to AITD and type 1 diabetes coexistent with AITD in
      Japanese population.

PMID- 14679108
TI  - Epitope analysis of GAD65 autoantibodies in Japanese patients with autoimmune
      diabetes.
AB  - Type 1 diabetes is an organ-specific autoimmune disease characterized by T cell
      mediated destruction of pancreatic beta cells. In Japanese population, the
      incidence of type 1 diabetes in children is very low compared to European
      countries. However, there are more patients with type 1 diabetes in adults,
      including latent autoimmune diabetes in adults (LADA). The circulating
      autoantibodies to multiple islet autoantigens including GAD, insulin, and IA-2
      are the important immunological features of type 1 diabetes. The prevalences of
      anti-islet autoantibodies in patients with Japanese type 1 diabetes are 60-70%
      for GAD autoantibodies, 45-50% for insulin autoantibodies (IAA), and 60-65% for
      IA-2 autoantibodies at disease onset, which are similar to those reported in
      Caucasian patients. With combinatorial analysis of these autoantibodies, 90% of
      patients express at least one of these autoantibodies and are classified as type
      1A diabetes. Although the majority of patients with type 1 diabetes are young,
      lean, and ketosis-prone, there are a number of patients with type 1 diabetes
      initially diagnosed as having type 2 diabetes at disease onset called LADA. These
      patients with LADA often progress toward an insulin-deficient state within
      several years after diagnosis. High levels of GAD autoantibodies have a high
      predictive value for future insulin deficiency in LADA. Further, epitope analysis
      of GAD65 autoantibodies may be helpful to predict future insulin dependency in
      LADA patients. In conclusion, Japanese patients with type 1 diabetes are
      clinically heterogeneous and the determination of immunological features are
      helpful to clarify the characteristics of the Japanese type 1 diabetic syndrome.

PMID- 14679109
TI  - A little citadel of light in a malignant sea of darkness.

PMID- 14679110
TI  - Her2-neu: a target in lung cancer?

PMID- 14679111
TI  - Cancer of the skin: a forgotten problem in Europe.

PMID- 14679112
TI  - Is there still a role for neoadjuvant chemotherapy in head and neck cancer?
AB  - After approximately 20 years of conflicting results from chemotherapy in
      randomized trials in advanced head and neck cancer, three meta-analyses reviewed
      its use. All three concluded that chemotherapy was associated with a
      statistically significant advantage in survival, but that this was low (4%
      absolute benefit at 2 and 5 years). The improvement in survival was mainly based
      on the more robust improvement obtained with the concomitant use of chemotherapy
      and radiotherapy. Induction chemotherapy, in particular, was not associated with
      any relevant survival advantage. This article reviews current indications for
      neoadjuvant chemotherapy in advanced head and neck cancer. Implications for
      current and future research are discussed.

PMID- 14679113
TI  - Indolent lymphoma: the pathologist's viewpoint.
AB  - Indolent lymphomas have recently been the object of numerous studies, which have
      focused on new aspects relevant both for the better comprehension of their
      histogenesis and the identification of new therapeutic strategies. As marginal
      zone lymphoma (MZL) represents the category of indolent lymphomas that has
      obtained more benefit from such an approach, the authors focused on the most
      recent achievements and not yet solved controversies in this area. In spite of
      their postulated common derivation, the three categories of MZL of the WHO
      Classification appear dissimilar. In fact, they show significant molecular
      differences among them as well as a certain heterogeneity within each group. By
      no means, there is a cogent need of more refined tools to revise these neoplasms
      and to produce a more rational grouping. The recent identification of the IRTA
      gene family corresponding to IG-like receptors differentially expressed in B
      cells might contribute to their better understanding.

PMID- 14679114
TI  - Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in
      HER2-positive non-small-cell lung cancer.
AB  - BACKGROUND: Trastuzumab provides significant clinical benefits in HER2-positive
      metastatic breast cancer patients when administered in combination with
      chemotherapy. Chemotherapy has also been shown to be beneficial in some patients
      with advanced non-small-cell lung cancer (NSCLC). The present randomized phase II
      trial examined the effect of adding trastuzumab to a standard chemotherapeutic
      combination (gemcitabine-cisplatin) in patients with HER2-positive NSCLC.
      PATIENTS AND METHODS: Patients with untreated stage IIIB/IV HER2-positive NSCLC
      received up to six 21-day cycles of gemcitabine 1250 mg/m(2) (days 1 and 8) and
      cisplatin 75 mg/m(2) (day 1). Patients in the trastuzumab arm received
      trastuzumab 4 mg/kg intravenously (i.v.) followed by 2 mg/kg/week i.v. until
      progression. RESULTS: Of 619 patients screened, 103 were eligible. Fifty-one
      patients were treated with trastuzumab plus gemcitabine-cisplatin and 50 with
      gemcitabine-cisplatin alone. Efficacy was similar in the trastuzumab and control
      arms: response rate 36% versus 41%; median time to progression 6.3 versus 7.2
      months; and median progression-free survival (PFS) 6.1 versus 7 months. Response
      rate (83%) and median PFS (8.5 months) appeared relatively good in the six
      trastuzumab-treated patients with HER2 3+ or fluorescence in situ hybridization
      (FISH)-positive NSCLC. Addition of trastuzumab to gemcitabine-cisplatin was well
      tolerated, side-effects were as expected, and trastuzumab did not exacerbate the
      known toxicity of gemcitabine and cisplatin. Symptomatic cardiotoxicity was
      observed in one trastuzumab-treated patient. Serum trastuzumab concentrations in
      the presence of gemcitabine-cisplatin were comparable to those of trastuzumab
      alone. CONCLUSIONS: Trastuzumab plus gemcitabine-cisplatin is well tolerated.
      Clinical benefit was not observed. Although HER2 3+/FISH-positive patients may
      benefit from trastuzumab, the subgroup is too small to provide definitive
      information. No significant effect of gemcitabine-cisplatin on trastuzumab
      pharmacokinetics was observed.

PMID- 14679115
TI  - Epidermal growth factor receptor overexpression correlates with a poor prognosis
      in completely resected non-small-cell lung cancer.
AB  - BACKGROUND: We designed a prospective study to test epidermal growth factor
      receptor (EGFR) expression by immunohistochemistry (IHC) in resected stage I-IIIA
      non-small-cell lung cancer (NSCLC) and to correlate overexpression with survival.
      PATIENTS AND METHODS: EGFR expression was evaluated in 130 consecutive NSCLC
      patients after radical surgery (60 squamous cell carcinomas, 48 adenocarcinomas,
      22 large cell carcinomas: stage I, 41 (31%); stage II, 37 (29%) and stage IIIA,
      52 (40%). RESULTS: Overall, 101 of 130 (78%) specimens expressed EGFR, and with a
      cut-off value of 10% positive cells 48 cases (37%) were classified as positive.
      At univariate analysis, EGFR was significantly more expressed in stage III (50%)
      than stage I (20%) and stage II (25%) (P <0.03). No correlation with histotype
      was found. After a median follow-up of 84 months, both median survival time (18
      versus 50 months), 2-year (43% versus 70%) and 5-year (31% versus 46%) survival
      rates of positive cases were significantly lower than negative ones [P <0.001;
      hazard ratio 1.96; 95% confidence interval (CI) 1.16-3.30]. At the multivariate
      analysis, EGFR overexpression and stage emerged as independent factors for cancer
      related mortality. CONCLUSION: In patients with radically resected stage I-IIIA
      NSCLC, EGFR overexpression predicts shorter survival, thus representing a
      valuable prognostic factor.

PMID- 14679116
TI  - Activity of a specific inhibitor, gefitinib (Iressa, ZD1839), of epidermal growth
      factor receptor in refractory non-small-cell lung cancer.
AB  - BACKGROUND: Gefitinib (Iressa(TM), ZD1839) is an orally active, selective
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Phase I
      studies showed that it is well tolerated, with evidence of tumor regression in
      patients with advanced non-small-cell lung cancer (NSCLC). Therefore, we aimed to
      assess the antitumor activity and tolerability of gefitinib in a series of
      patients with previously treated, advanced NSCLC, as a part of a compassionate
      use program. PATIENTS AND METHODS: To be eligible, all patients were required to
      have histologically or cytologically proven advanced or metastatic NSCLC, prior
      chemotherapy with at least one cisplatin-containing chemotherapy regimen or
      contraindication to cytotoxic drugs, Eastern Cooperative Oncology Group
      performance status < or =2, and adequate hematological, renal and hepatic
      parameters. All patients provided signed informed consent. Patient re-evaluation
      was performed every 4-6 weeks. RESULTS: Seventy-three consecutive patients were
      enrolled. Response rate, including complete and partial response, was 9.6%; an
      additional 43.8% of patients achieved stable disease, for an overall disease
      control of 53.4%. EGFR1 status was evaluated by immunocytochemistry in 25
      patients. According to EGFR1 immunoreactivity all responses were observed with
      medium/strong imunoreactivity while three out of four responses were observed in
      high expressive patients. Median survival for all patients was 4 months while it
      reached 6 months for patients with disease control. The 1-year survival rate was
      13.1% for the entire series and 23.2% for patients with disease control. Non
      hematological toxicity was generally mild. CONCLUSION: Gefitinib has promising
      activity with a good toxicity profile in patients with progressive NSCLC who have
      received one or two prior chemotherapy regimens. A possible relationship within
      response and EGFR1 expression is suggested.

PMID- 14679117
TI  - Randomised, multicentre phase II study assessing two doses of docetaxel (75 or
      100 mg/m2) as second-line monotherapy for non-small-cell lung cancer.
AB  - BACKGROUND: The survival benefit associated with first-line chemotherapy in
      advanced lung cancer led to the need for second-line chemotherapy. Docetaxel
      (Taxotere) has proven efficacy in both settings. This study evaluated the safety
      and efficacy of two doses of docetaxel in patients with non-small-cell lung
      cancer who had failed first-line platinum-based chemotherapy. PATIENTS AND
      METHODS: In total, 182 patients from 24 French centres were randomised and
      treated with either docetaxel 75 mg/m(2) (arm A) or 100 mg/m(2) (arm B) every 3
      weeks. Baseline characteristics were well balanced, except more patients in arm A
      had metastatic disease (91.4% versus 78.7%) and therefore the median number of
      sites involved for arm A was three compared with two for arm B. RESULTS: Median
      time to treatment failure was 1.34 months [95% confidence interval (CI) 1.28
      1.64] for arm A and 1.64 months (95% CI 1.34-2.62) for arm B. Median overall
      survival was 4.7 months (95% CI 3.8-5.9) for arm A versus 6.7 months (95% CI 4.8
      7.1) for arm B. According to a blinded expert panel, disease control was achieved
      in 35 (43.8%) patients in arm A and 39 (49.4%) patients in arm B. More patients
      in arm B experienced grade 3-4 neutropenia (B: 72.7% versus A: 44.0%), asthenia
      (B: 20.2% versus A: 10.8%) and infection (B: 6.7% versus A: 2.2%). Three
      treatment-related deaths were reported in each arm. CONCLUSIONS: The optimal
      docetaxel dosage in this second-line setting is 75 mg/m(2), as it has a more
      favourable safety profile and on balance a similar efficacy to the 100 mg/m(2)
      dose.

PMID- 14679118
TI  - A phase II study of cisplatin and docetaxel administered as three consecutive
      weekly infusions for advanced non-small-cell lung cancer in elderly patients.
AB  - BACKGROUND: To evaluate the efficacy and safety of treatments for advanced non
      small-cell lung cancer in elderly patients aged 75 years or older, we conducted a
      phase II study of cisplatin and docetaxel administered in three consecutive
      weekly infusions. PATIENTS AND METHODS: The eligibility criteria for the study
      included the presence of chemotherapy-naive advanced non-small-cell lung cancer,
      age > or =75 years, Eastern Cooperative Oncology Group performance status of 0 or
      1, a measurable lesion, adequate organ functions and signed informed consent. The
      chemotherapy regimen consisted of cisplatin (25 mg/m(2)) and docetaxel (20
      mg/m(2)) on days 1, 8 and 15 every 4 weeks. RESULTS: Between February 2000 and
      March 2002, 34 elderly patients with non-small-cell lung cancer were enrolled in
      the study and 33 patients were treated. Two complete responses and 15 partial
      responses were obtained for an objective response rate of 52% in 33 treated
      patients. The median survival period was 15.8 months, and the 1-year survival
      rate was 64%. Toxicities were mild with no grade 4 toxicities. Only grade 3
      leukopenia (6%), neutropenia (12%), anemia (3%), hyponatremia (3%) and
      nausea/vomiting (3%) were observed. CONCLUSION: Cisplatin and docetaxel
      administered in three consecutive weekly infusions was safe and effective for the
      treatment of elderly patients with chemotherapy-naive non-small-cell lung cancer.

PMID- 14679119
TI  - Pharmacokinetic analysis of combination chemotherapy with carboplatin and
      etoposide in small-cell lung cancer patients undergoing hemodialysis.
AB  - BACKGROUND: The aim of this study was to use pharmacokinetic analysis to
      investigate the efficacy and toxicity of combined chemotherapy with carboplatin
      (CBDCA) and etoposide (ETP) in small-cell lung cancer (SCLC) patients with
      chronic renal failure undergoing hemodialysis (HD). PATIENTS AND METHODS: Three
      SCLC patients with chronic renal failure undergoing HD were treated with CBDCA
      (300 mg/m(2)) on day 1 and ETP (50 mg/m(2)) on days 1 and 3, followed by HD 1 h
      after completing the administration of anticancer agents on each day. The
      pharmacokinetic analysis of CBDCA and ETP was planned for at least the first two
      courses of the chemotherapy in each patient. RESULTS: Two complete responses and
      one partial response were achieved in the three patients. Two patients
      experienced grade 3/4 neutropenia and required blood transfusion due to
      thrombocytopenia and anemia. Non-hematological toxicities were moderate. The
      pharmacokinetic analysis revealed that the platinum and the ETP concentrations in
      the plasma were similar to those in patients with normal renal function during
      the first 24 h, while the platinum still remained in the plasma for over 90 h.
      CONCLUSIONS: Chemotherapy with CBDCA (300 mg/m(2) on day 1) and ETP (50 mg/m(2)
      on day 1, 3) as used in the present study may be a suitable regimen for SCLC
      patients undergoing HD, although careful attention should be given to
      hematological toxicities.

PMID- 14679120
TI  - Lack of correlation between immunohistochemical expression of E2F-1, thymidylate
      synthase expression and clinical response to 5-fluorouracil in advanced
      colorectal cancer.
AB  - BACKGROUND: The level of the enzyme thymidylate synthase (TS) is known to
      inversely correlate with the clinical activity of 5-fluorouracil (FU) in advanced
      colorectal cancer patients. Since the correlation is not very strong, we have
      retrospectively analyzed the expression of E2F-1 in tumor samples or metastases
      from 25 patients with advanced colorectal cancer, homogeneously treated with an
      FU-based regimen. E2F-1 is a transcription factor regulating the expression of TS
      along with other crucial DNA synthesis related enzymes. MATERIALS AND METHODS:
      E2F-1 expression was analyzed by immunohistochemistry using the anti-E2F-1
      monoclonal antibody KH95, scoring 2000 cells/case. Expression of TS was evaluated
      by immunohistochemistry using a rabbit anti-human polyclonal antibody. RESULTS:
      The level of E2F-1 expression did not correlate with TS expression, although a
      trend for correlation between E2F-1 level and maximal tumor shrinkage was
      observed (r = 0.42; P = 0.054). CONCLUSIONS: In spite of previous reports
      demonstrating that E2F-1 quantified by rt-PCR and western blot correlates with TS
      and could be used as a predictor to select colorectal cancer patients more likely
      to respond to FU treatment, our data suggest that, under these experimental
      conditions, immunohistochemistry cannot be used for such selection.

PMID- 14679121
TI  - Continuous infusion of hepatic arterial irinotecan in pretreated patients with
      colorectal cancer metastatic to the liver.
AB  - BACKGROUND: Irinotecan is an active drug in colorectal cancer. In patients with
      liver metastases, hepatic arterial infusion of irinotecan could theoretically
      result in higher exposure to the drug. In order to determine the efficacy of
      hepatic arterial irinotecan we conducted a phase II study in pretreated patients
      with liver metastases of colorectal cancer. PATIENTS AND METHODS: Patients with
      measurable liver metastases of colorectal cancer with World Health Organization
      performance status (WHO PS) <2 were treated with a 5-day continuous infusion of
      hepatic arterial irinotecan every 3 weeks at a dose of 20 mg/m(2)/day. RESULTS:
      Of the 25 patients included, 22 were evaluable for response. Three of 22 patients
      (13.6%) had a partial response, nine (40.9%) had stable disease and 10 (45.4%)
      had progressive disease. No complete responses were observed. Median time to
      progression was 2.8 (range 1.2-23.8) months. Major toxicities were vomiting and
      diarrhea. There was no major hematological toxicity. CONCLUSIONS: Five-day
      continuous hepatic arterial infusion of irinotecan 20 mg/m(2)/day has low
      activity in patients with liver metastases of colorectal cancer previously
      treated by chemotherapy.

PMID- 14679122
TI  - Phase II study of irinotecan and 5-fluorouracil/leucovorin in patients with
      primary refractory or relapsed advanced oesophageal and gastric carcinoma.
AB  - BACKGROUND: The purpose of this study was to assess the efficacy and toxicity of
      irinotecan and 5-fluorouracil (5-FU) in primary refractory or relapsed locally
      advanced or metastatic oesophagogastric (O-G) carcinoma. PATIENTS AND METHODS:
      Patients with documented progression on or within 3 months of chemotherapy were
      recruited between July 2000 and May 2002. Irinotecan (180 mg/m(2)) was given with
      5-FU (400 mg/m(2) bolus) and leucovorin (folinic acid) (125 mg/m(2)) followed by
      5-FU (1200 mg/m(2) infusion over 48 h) every 2 weeks. Response confirmed by
      computed tomography was assessed at 12 and 24 weeks. RESULTS: Thirty-eight of 40
      registered patients (95%) were assessable. Median follow-up was 9.3 months and
      median age was 59.0 years. Thirty-three patients (86.8%) had metastatic disease
      and 37 patients (97.4%) had previously received platinum-based chemotherapy.
      Overall response rate was 29% (95% confidence interval 15.4% to 45.9%) while an
      additional 34% had stable disease. Improvement in tumour-related symptoms
      included dysphagia 78.6%, reflux 60.0%, pain 54.5%, anorexia 64.3% and weight
      loss 72.7%. Grade 3/4 toxicities were anaemia 13.2%, neutropenia 26.4%, febrile
      neutropenia 5.2%, stomatitis 2.6%, nausea and vomiting 13.2% and diarrhoea 7.9%.
      Median failure-free survival was 3.7 months and median overall survival was 6.4
      months. CONCLUSION: 5-FU/irinotecan is a valuable regimen for second-line
      treatment in 5-FU/platinum-resistant O-G carcinoma.

PMID- 14679123
TI  - INK4/ARF germline alterations in pancreatic cancer patients.
AB  - BACKGROUND: Roughly 40% of germinal mutations in melanoma families (MF) affect
      p16(INK4a) and p14(ARF). We investigated the association between INK4/ARF
      alterations and the occurrence of pancreatic cancer in MF and in sporadic
      pancreatic cancer (SPC) patients. PATIENTS AND METHODS: Forty-nine MF, 66 SPC
      cases and 54 controls were enrolled. The INK4/ARF locus was screened. RESULTS: As
      compared with the general population, the risk of pancreatic cancer (PC) was
      increased 9.4-fold [95% confidence interval (CI) 2.7-33.4] and 2.2-fold (95% CI
      0.8-5.7) in G101W-positive and -negative MF, respectively, while mean ages at
      onset were 61 and 77 years, respectively. A 1.7 (95% CI 1.06-2.79) increased risk
      of cancer at any site was observed among first-degree relatives of SPC cases as
      compared with controls. The G101W founder mutation was detected in 4% of SPC
      cases but the rate increased to 13% when tumor clustering in either branch of
      families was taken into account. One G101W-positive PC patient with a melanoma in
      a first-degree relative harbored a germline deletion of the second allele,
      including exon 1B. CONCLUSIONS: The presence of a deletion including exon 1B in
      two PC patients points to the involvement of p14(ARF) in the development of PC
      and may suggest that the increased risk of PC in MF is caused by impairment of
      both loci.

PMID- 14679124
TI  - Epirubicin-cyclophosphamide adjuvant chemotherapy plus tamoxifen administered
      concurrently versus sequentially: randomized phase III trial in postmenopausal
      node-positive breast cancer patients. A GEICAM 9401 study.
AB  - BACKGROUND: A prospective randomized clinical trial was implemented to assess
      whether the concomitant or the sequential addition of tamoxifen to chemotherapy
      provides improved clinical benefit in the adjuvant treatment of breast cancer in
      postmenopausal patients. PATIENTS AND METHODS: Four-hundred and eighty-five
      patients with node-positive operable disease were randomized to receive tamoxifen
      (20 mg/day) concomitantly (CON) or sequentially (SEQ) to EC chemotherapy
      (epirubicin 75 mg/m(2) + cyclophosphamide 600 mg/m(2) on day 1, every 21 days for
      four cycles). RESULTS: In the 474 fully evaluable patients there were 96 events;
      eight being second neoplasms and 88 being related to the breast cancer. Of these,
      48 of 88 occurred in the CON arm and 40 of 88 in the SEQ arm. The Kaplan-Meier
      estimation of disease-free survival (DFS) at 5 years was 70% in the CON and 75%
      in the SEQ group (log-rank test, P = 0.43). Adjusted hazard ratio for treatment
      was 1.11 (95% confidence interval 0.71-1.73; P = 0.64). CONCLUSION: This study
      fails to show an advantage of one treatment arm over the other, but a trend,
      albeit non-significant, appears to favor the sequential addition of tamoxifen to
      epirubicin + cyclophosphamide and, as such, warrants further investigation.

PMID- 14679125
TI  - The impact of sentinel node biopsy and axillary staging strategy on hospital
      costs.
AB  - BACKGROUND: The aim of the study was to evaluate total hospital costs of three
      different sentinel node biopsy (SNB) protocols compared to those of diagnostic
      axillary lymph node dissection (ALND). PATIENTS AND METHODS: The study included
      237 consecutive breast cancer patients who underwent SNB with frozen section
      diagnosis. The sequence of the treatment procedures for each patient was
      recorded. The sequences of treatment procedures for the same patients were
      evaluated using three hypothetical scenarios: diagnostic ALND, SNB without frozen
      section diagnosis and SNB as day case surgery prior to the breast operation. The
      total hospital costs were calculated in all protocols. RESULTS: The hospital
      costs per patient were 3750euro;. The hospital costs per patient would have been
      3020euro; when using the ALND model, 4087euro; had the frozen section not been
      applied and 4573euro; using 'SNB as day case surgery' model. The costs with or
      without frozen section diagnosis would have been equal with a threshold false
      negative rate of 35%. CONCLUSIONS: SNB seems to be associated with higher
      hospital costs than diagnostic ALND. Frozen section diagnosis seems to be
      worthwhile as long as the false negative rate is <35%.

PMID- 14679126
TI  - Evidence for in vivo synergism between docetaxel and gemcitabine in patients with
      metastatic breast cancer.
AB  - BACKGROUND: The docetaxel and gemcitabine combination is active as salvage
      therapy in taxane-resistant/refractory patients with metastatic breast cancer
      (MBC). We conducted a phase II study to determine if this activity is due to an
      in vivo synergistic effect. PATIENTS AND METHODS: Women with measurable MBC, who
      were refractory or resistant to docetaxel monotherapy as first- or second-line
      treatment, were enrolled. Patients with progressive disease (PD) or stable
      disease (SD) after receiving at least four cycles of docetaxel received
      gemcitabine 900 mg/m(2) on days 1 and 8 plus docetaxel 100 mg/m(2 )on day 8,
      every 3 weeks. Granulocyte colony-stimulating factor could be used
      prophylactically in patients who experienced grade 3/4 neutropenia after the
      first cycle. RESULTS: Between January 1999 and March 2002, 173 courses of
      docetaxel and gemcitabine were administered to 50 patients. The median number of
      metastatic sites was two (range one to three). Forty-six percent of patients
      responded (three complete responses, 20 partial responses), whereas 28% had SD
      and 26% had PD. The median duration of response was 6.1 +/- 2.4 months. The
      median time to disease progression was 7.5 months (range 1-25) and the overall
      median survival was 15 months (range 3-57). Neutropenia was the only National
      Cancer Institute Common Toxicity Criteria grade 4 toxicity (in seven patients).
      Hematological grade 3 toxicities included neutropenia in 12 patients,
      thrombocytopenia in seven and anemia in one, while non-hematological toxicities
      were mild and manageable. CONCLUSIONS: The high overall response rate of the
      docetaxel plus gemcitabine combination after docetaxel failure in patients with
      MBC can be attributed to an in vivo synergism between the two drugs. These data
      warrant confirmation in a randomized study.

PMID- 14679127
TI  - Long-term survival in a phase III, randomised study of topotecan versus
      paclitaxel in advanced epithelial ovarian carcinoma.
AB  - BACKGROUND: We have continued to monitor the survival of patients randomised in a
      previously reported multicentre phase III study of topotecan versus paclitaxel in
      patients with advanced epithelial ovarian cancer who had failed one prior
      platinum-based regimen. PATIENTS AND METHODS: Patients with bidimensionally
      measurable disease were randomised to topotecan (1.5 mg/m(2)/day for 5 days) or
      paclitaxel (175 mg/m(2)/day as a 3-h infusion) every 21 days. Patients were
      eligible for treatment with the alternate therapy at third line. The European
      Organisation for Research and Treatment of Cancer Quality of Life (EORTC QOL)-C30
      questionnaire was also used to measure eight symptoms at baseline and during each
      course (pain, anorexia, diarrhoea, fatigue, nausea and vomiting, dyspnea,
      constipation and insomnia). RESULTS: A total of 226 patients were evaluable for
      response. Demographic characteristics were similar in both treatment groups, as
      were results of the EORTC QOL-30 questionnaire. For the topotecan group, median
      time to progression was 18.9 weeks (range <1 to 92.6+ weeks; 25% censored), and,
      for paclitaxel, 14.7 weeks (range <1 to 137.3+ weeks; 12.3% censored); P = 0.076.
      At 4 years post-randomisation, median survival in the topotecan group was 63.0
      weeks (range <1 to 238.4+ weeks; 20.5% censored) and, for paclitaxel, 53.0 weeks
      (range <1 to 226.3+ weeks; 12.3% censored); P = 0.44. CONCLUSION: Topotecan
      continues to demonstrate comparable efficacy and survival to paclitaxel with
      manageable and non-cumulative haematological toxicity. Non-haematological
      toxicity was generally mild for both groups. The long-term survival rate
      indicates substantial therapeutic benefit for this group of patients receiving
      topotecan at relapse of ovarian cancer.

PMID- 14679128
TI  - HER-2 overexpression is an independent marker of poor prognosis of advanced
      primary ovarian carcinoma: a multicenter study of the GINECO group.
AB  - BACKGROUND: Despite numerous studies, no biological marker has been identified
      that accurately predicts prognosis of advanced ovarian cancer. Tumors from a
      homogeneous population of 117 patients with a stage III/IV ovarian cancer,
      enrolled in a multicenter prospective GINECO clinical trial were analyzed
      retrospectively. PATIENTS AND METHODS: All patients received the same platinum
      based combination therapy and were followed-up for a median of 68 months. Tumor
      expression of Ki67, BCL-2, BAX, P53 or c-erbB-2 proteins was evaluated
      immunohistochemically on paraffin-embedded tissues and their prognostic impact
      analyzed. RESULTS: The median rate of Ki67-positive nuclear area was 30%. BCL-2,
      BAX and P53 proteins were expressed in 52, 54 and 71% of the tumors,
      respectively, while HER-2 protein was overexpressed in 16%. Only HER-2
      overexpression was significantly associated with shorter progression-free
      survival and overall survival. According to our multivariate analysis, the HER-2
      prognostic impact was independent of classical clinical prognostic factors.
      CONCLUSION: HER-2 appeared to influence the outcome of advanced ovarian cancer
      patients included in a clinical trial with prolonged follow-up, thereby
      suggesting that HER-2 is a potential target for treatment of this cancer.

PMID- 14679130
TI  - Survival data and prognostic factors seen in Pakistani patients with esophageal
      cancer.
AB  - BACKGROUND: Esophageal cancer is common in Pakistan. An attempt has been made for
      the first time to look at the survival data and prognostic factors associated
      with esophageal cancer in this region. PATIENTS AND METHODS: We did a
      retrospective review of 263 cases seen at the Aga Khan University Hospital in
      Karachi. Data analysis was done using the Kaplan-Meier method and the Cox
      proportional hazard model. RESULTS: Squamous cell carcinoma was noted in 81% of
      the cases, whereas adenocarcinoma was the second most common. At the time of
      diagnosis, early-stage disease was found in 25%, locally advanced in 41% and
      metastatic in 34% of all cases. Mean age at diagnosis was 56 years, with 59%
      males and 41% females. Survival data were available in 89 cases. Median survival
      was 7 months. On univariate analysis, the following factors were of prognostic
      significance: obstruction, histology, albumin level at diagnosis, age and
      platelet count. On multivariate analysis, three factors were found prognostic:
      presence or absence of obstruction, squamous cell carcinoma versus adenocarcinoma
      and platelet count. CONCLUSIONS: We found that patients with squamous cell
      carcinoma and absence of thrombocytopenia and obstruction had a better overall
      survival. However, this is a limited retrospective analysis; we therefore
      recommend that these prognostic factors be evaluated in larger studies.

PMID- 14679129
TI  - Adoptive transfer of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T
      cells with in vitro antitumor activity boosts LMP2-specific immune response in a
      patient with EBV-related nasopharyngeal carcinoma.
AB  - BACKGROUND: The outcome of patients with nasopharyngeal carcinoma (NPC)
      presenting as advanced-stage disease or failing conventional radio-chemotherapy
      is poor. Thus, additional forms of effective, low-toxicity treatment are
      warranted to improve NPC prognosis. Since NPC is almost universally associated
      with Epstein-Barr virus (EBV), cellular immunotherapy with EBV-specific cytotoxic
      T lymphocytes (CTLs) may prove a successful treatment strategy. Patient and
      methods A patient with relapsed NPC, refractory to conventional treatments,
      received salvage adoptive immunotherapy with EBV-specific CTLs reactivated ex
      vivo from a human leukocyte antigen-identical sibling. EBV-specific immunity, as
      well as T-cell repertoire in the tumor, before and after immunotherapy, was
      evaluated. RESULTS: CTL transfer was well tolerated, and a temporary
      stabilization of disease was obtained. Moreover, notwithstanding the short in
      vivo duration of allogeneic CTLs, immunotherapy induced a marked increase of
      endogenous tumor-infiltrating CD8+ T lymphocytes, and a long-term increase of
      latent membrane protein 2-specific immunity. CONCLUSIONS: Preliminary data
      obtained in this patient indicate that EBV-specific CTLs are safe, may exert
      specific killing of NPC tumor cells in vitro, and induce antitumor effect in
      vivo.

PMID- 14679132
TI  - Incidence and risk factors for central nervous system occurrence in elderly
      patients with diffuse large-B-cell lymphoma: influence of rituximab.
AB  - BACKGROUND: The incidence of secondary central nervous system (CNS) occurrences
      in diffuse large-B-cell lymphoma is not sufficiently high to warrant the use of
      CNS prophylaxis in all patients. The addition of rituximab increases the complete
      response rate and prolongs event-free and overall survival in elderly patients
      with such lymphoma. PATIENTS AND METHODS: We analyzed a cohort of 399 elderly
      patients with lymphoma prospectively treated with eight cycles of CHOP with or
      without rituximab in order to assess if rituximab decreases the risk of CNS
      localization. Prophylaxis of CNS disease was not part of the treatment protocol.
      RESULTS: We observed 20 CNS occurrences: 12 on therapy, four after partial
      remission and four following complete remission. In three patients, the CNS was
      the only site of relapse. In a multivariate analysis, increased age-adjusted
      International Prognostic Index (IPI) was the only independent predictive factor
      of CNS recurrence. Only three of 20 patients are alive with a follow-up of 24
      months. CONCLUSIONS: Rituximab did not influence the risk of CNS occurrence,
      possibly because of low rituximab diffusion. Direct intrathecal administration of
      rituximab could overcome this problem. We also confirmed that CNS occurrence is
      related to IPI as well as very poor prognosis of relapses occurring on therapy.

PMID- 14679131
TI  - VEPEMB in elderly Hodgkin's lymphoma patients. Results from an Intergruppo
      Italiano Linfomi (IIL) study.
AB  - BACKGROUND: In advanced age the prognosis of Hodgkin's lymphoma (HL) is poor,
      but, as a consequence of the low incidence of HL in the elderly, prospective
      studies are lacking and the best treatment strategy is difficult to define.
      PATIENTS AND METHODS: One-hundred and five HL patients over 65 years of age were
      treated homogeneously with an original reduced-intensity regimen designed for HL
      in the elderly containing vinblastine, cyclophosphamide, procarbazine, etoposide,
      mitoxantrone and bleomycin (VEPEMB). Forty-eight early stage (IA-IIA) patients
      received three courses of VEPEMB followed by involved field irradiation. Fifty
      seven advanced stage (IIB-IV) patients received six courses followed by
      radiotherapy limited to the areas of bulky disease. RESULTS: Mean age was 71
      years (range 66-83). Co-morbidities were present in 39 patients (37%). A
      treatment plan modification for poor tolerance or toxicity was needed in 18
      patients. Results were satisfactory, even if they were better in early rather
      than in advanced stage disease: complete response rate 98% versus 58% (P <0.01);
      5-year failure-free survival 79% versus 34% (P <0.01). The results were affected
      by advanced stage, systemic symptoms and co-morbidity but they were not
      influenced by age itself. CONCLUSIONS: VEPEMB is an effective and low toxic
      regimen for HL in the elderly. Co-morbidity is a prognostic factor more important
      than age itself.

PMID- 14679133
TI  - Primary treatment of multiple myeloma with thalidomide, vincristine, liposomal
      doxorubicin and dexamethasone (T-VAD doxil): a phase II multicenter study.
AB  - BACKGROUND: High-dose chemotherapy with autologous stem cell transplantation
      after initial cytoreductive chemotherapy with the combination vincristine,
      doxorubicin and dexamethasone (VAD) is considered an effective therapy for many
      patients with newly diagnosed, symptomatic multiple myeloma. Response to initial
      cytoreductive chemotherapy is important for the long-term outcome of such
      patients. Thalidomide has recently shown significant antimyeloma activity. We
      studied the efficacy and toxicity of the combination of a liposomal doxorubicin
      containing VAD regimen with thalidomide, administered on an outpatient basis, as
      initial cytoreductive treatment in previously untreated patients with symptomatic
      myeloma. PATIENTS AND METHODS: Thirty-nine myeloma patients were treated with
      vincristine 2 mg intravenously (i.v.), liposomal doxorubicin 40 mg/m(2) i.v.
      administered as single dose on day 1, and dexamethasone 40 mg per os daily for 4
      days. Dexamethasone was also given on days 15-18 of the first cycle of treatment.
      The regimen was administered every 4 weeks for four courses. Thalidomide was
      given daily at a dose of 200 mg at bedtime. Response to treatment was evaluated
      after four cycles of treatment. After completion of four cycles, the patients
      were allowed to proceed to high-dose chemotherapy or to receive two additional
      cycles of the same treatment. RESULTS: On an intention-to-treat basis, 29 of the
      39 patients (74%) responded to treatment. Four patients (10%) achieved complete
      and 25 (64%) partial response. Three patients (8%) showed minor response and
      seven (18%) were rated as non-responders. Major grade 3 or 4 toxicities consisted
      of neutropenia (15%), thrombocytopenia (15%), deep vein thrombosis (10%),
      constipation (10%), skin rash (5%) and peripheral neuropathy (5%). Two patients
      (5%) experienced early death due to infection. CONCLUSIONS: The combination of
      vincristine, liposomal doxorubicin, and dexamethasone (VAD doxil) with
      thalidomide is an effective and relatively well-tolerated initial cytoreductive
      treatment. Prospective randomized studies are required in order to assess the
      effect of this regimen on the long-term outcome of patients with multiple
      myeloma.

PMID- 14679134
TI  - Increased levels of viable circulating endothelial cells are an indicator of
      progressive disease in cancer patients.
AB  - BACKGROUND: There is accumulating evidence from preclinical studies that
      circulating endothelial cells (CECs) play an important role in neovascularization
      and tumor growth. The role of CECs in human cancer progression is sparsely
      investigated. We therefore analyzed CECs in peripheral blood of cancer patients.
      In addition, we correlated CEC levels in these patients with plasma levels of
      cytokines that are known to mobilize CECs in experimental models. PATIENTS AND
      METHODS: Viable CECs were isolated, quantified and cultured from cancer patients'
      whole blood by using magnetic beads coupled to an antibody directed against
      CD146, a pan-endothelial marker. Viable cells were visualized by calceinAM
      staining. Positive staining for specific endothelial cell markers [i.e. von
      Willebrand factor, CD31, vascular endothelial cell growth factor (VEGF) receptor
      2] was used to confirm the endothelial phenotype. RESULTS: Cancer patients with
      progressive disease (95 patients) had on average 3.6-fold more CECs than healthy
      subjects (46 patients, P <0.001). Patients (17) with stable disease had CEC
      numbers equal to that circulating in healthy subjects (P = 0.69). A subset of in
      vitro cultured CECs incorporated into endothelial layers and formed colonies.
      Plasma levels of cytokines that are thought to mobilize CECs from the bone marrow
      [VEGF, placental growth factor, stromal cell derived factor 1alpha and stem cell
      factor (71 patients)] did not correlate with CEC amounts. The levels of viable
      CECs in cancer patients were modified by granulocyte colony-stimulating factor
      treatment and chemotherapy. CONCLUSION: In progressive cancer patients, the
      amount of CECs is increased. These CECs are viable and may contribute to vessel
      formation. The number of CECs is influenced by anticancer treatment.

PMID- 14679135
TI  - Anthracyclines during pregnancy: embryo-fetal outcome in 160 patients.
AB  - BACKGROUND: Anthracyclines are essential for the treatment of malignancies
      observed in pregnant patients. Knowledge of the potential side-effects of
      chemotherapy on the developing fetus is essential for patient counseling.
      PATIENTS AND METHODS: We collected information concerning patients treated with
      anthracyclines during pregnancy from a review of literature between 1976 and 2001
      and our experience. The events analyzed were malformations, fetal death and
      spontaneous abortion. A chi(2) test with a Yates correction was used to compare
      the distribution of severe events. RESULTS: A total of 160 patient pregnancies
      were analyzed. The fetal outcome was frequently normal (73%). Abnormalities
      included malformations (3%), fetal death (9%), spontaneous abortion (3%), fetal
      complications (8%) and prematurity (6%). Fetal death was often directly
      consecutive to maternal death (40%). Unfavorable fetal outcome was significantly
      more frequent in leukemia patients (P = 0.001). In patients with solid tumors,
      the first trimester was significantly associated with more complications (P =
      0.029). The risk of severe fetal toxicity was increased 30-fold when the dose of
      doxorubicin per cycle exceeded 70 mg/m(2) (P = 0.037). CONCLUSIONS:
      Anthracyclines may induce embryo-fetal toxicity. Nevertheless the risk seems low,
      especially after the first trimester and using doses of doxorubicin below 70
      mg/m(2).

PMID- 14679136
TI  - Analysis of dihydrofolate reductase and reduced folate carrier gene status in
      relation to methotrexate resistance in osteosarcoma cells.
AB  - BACKGROUND: To evaluate the impact of dihydrofolate reductase (DHFR) and reduced
      folate carrier (RFC) genes on methotrexate (MTX) resistance in osteosarcoma cells
      in relation to retinoblastoma (RB1) gene status. MATERIALS AND METHODS: A series
      of human osteosarcoma cell lines-either sensitive or resistant to MTX-and 16
      osteosarcoma tumour samples were used in this study. RESULTS: In U-2OS MTX
      resistant variants, and in other RB1-positive cell lines, MTX resistance was
      associated with increased levels of DHFR and with a slight decrease of RFC gene
      expression. In Saos-2 MTX-resistant variants, and in another RB1-negative cell
      line, development of MTX resistance was associated with a decrease in expression
      of RFC, without any significant involvement of DHFR. In osteosarcoma clinical
      samples, amplification of the DHFR gene at clinical onset appeared to be more
      frequent in RB1-positive compared with RB1-negative tumours. CONCLUSIONS:
      Amplification of the DHFR gene may occur more frequently in the presence of RB1
      mediated negative regulation of its activity and can be present at clinical onset
      in osteosarcoma patients. Simultaneous evaluation of RFC, DHFR and RB1 gene
      status at the time of diagnosis may become the basis for the identification of
      potentially MTX-unresponsive osteosarcoma patients, who could benefit from
      treatment protocols with alternative antifolate drugs.

PMID- 14679137
TI  - Dose-dense regimen of temozolomide given every other week in patients with
      primary central nervous system tumors.
AB  - BACKGROUND: Temozolomide has shown activity and limited toxicity in patients with
      primary brain tumors at doses of 150-200 mg/m(2)/day on days 1-5 every 4 weeks.
      In this study, a new alternative dose-dense regimen of temozolomide was explored
      in patients with recurrent brain tumors. PATIENTS AND METHODS: In this study, we
      evaluated the safety, dose-limiting toxicity, maximum tolerated dose, recommended
      dose and activity of temozolomide given on days 1-3 and 14-16 every 28 days (one
      cycle). The starting daily dose was 200 mg/m(2) in a group of at least six
      patients, with subsequent increments of 50 mg/m(2) in groups of at least 12
      patients until unacceptable toxicity was reached. Oral ondansetron (8 mg) was
      given 1 h prior to temozolomide administration. McDonald's criteria were used to
      evaluate antitumor activity. RESULTS: Seventy patients with brain tumors entered
      this study. The median number of prior chemotherapy treatments was two (range 1
      3). Patients were assigned to one of four groups to receive temozolomide at daily
      doses of 200 (seven patients), 250 (13 patients), 300 (38 patients) and 350
      mg/m(2)/day (12 patients). The absence of dose-limiting toxicity at cycle 1 led
      us to establish dose recommendations based on toxicity after repeated cycles. A
      total of 23, 72, 192 and 83 cycles were given at daily doses of 200, 250, 300 and
      350 mg/m(2), respectively. Grade 3-4 thrombocytopenia was observed in 0/7, 1/13,
      5/38 and 4/12 patients treated at doses of 200, 250, 300 and 350 mg/m(2)/day,
      respectively. Grade 3-4 neutropenia was observed in 1/7, 0/13, 3/38 and 4/12
      patients treated with 200, 250, 300 and 350 mg/m(2)/day temozolomide,
      respectively. At a dose of 350 mg/m(2), sustained grade 2-3 thrombocytopenia did
      not allow treatment to be resumed at day 14 in >40% of patients, and this dose
      was considered to be the maximum tolerated dose. Thus, a dose of 300 mg/m(2)/day
      that was associated with <20% treatment delay due to sustained hematological
      toxicity was considered as the recommended dose. Objective responses were
      reported in 13 patients. CONCLUSIONS: Temozolomide can be given safely using a
      dose-dense regimen of 300 mg/m(2)/day for 3 consecutive days every 2 weeks in
      patients with recurrent brain tumors.

PMID- 14679138
TI  - Effect of re-treatment with gefitinib ('Iressa', ZD1839) after acquisition of
      resistance.

PMID- 14679140
TI  - Renal tubular damage in rasburicase: risks of alkalinisation.

PMID- 14679141
TI  - Vinorelbine, methotrexate and fluorouracil (VMF) as first-line therapy in
      metastatic breast cancer: significance of the time between initiation of adjuvant
      therapy and of therapy for metastatic breast cancer.

PMID- 14679142
TI  - Combination therapy of Thalidomide and Peginterferon in patients with progressive
      multiple myeloma.

PMID- 14679143
TI  - Ovarian ablation as adjuvant therapy for premenopausal women with breast cancer-
      another step forward.

PMID- 14679144
TI  - Is there a role for epidermal growth factor receptor inhibitors in breast cancer
      prevention?

PMID- 14679145
TI  - Study clarifies risk of breast, ovarian cancer among mutation carriers.

PMID- 14679146
TI  - Investigational drug access taken to task in lawsuit against FDA.

PMID- 14679147
TI  - Stat bite: Leading causes of death in the United States, 1980 vs. 2001.

PMID- 14679148
TI  - Epoetin for cancer patients: a boon or a danger?

PMID- 14679150
TI  - Community Clinical Oncology Program celebrates 20 years of trials and a few
      tribulations.

PMID- 14679152
TI  - Effect of epidermal growth factor receptor inhibitor on development of estrogen
      receptor-negative mammary tumors.
AB  - BACKGROUND: Although antiestrogens have been effective in preventing estrogen
      receptor (ER)-positive breast cancer, chemopreventive agents are still needed to
      prevent ER-negative breast cancer. Tyrosine kinase inhibitors are promising
      agents for the treatment and prevention of human cancers. ZD1839 (gefitinib or
      Iressa) is an orally active epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitor that blocks signal transduction pathways in epithelial cells. We
      examined whether ZD1839 blocks signal transduction and prevents the development
      of ER-negative breast cancer. METHODS: The ability of ZD1839 to block signal
      transduction in normal, immortalized, and malignant breast cells was assessed by
      western blotting with specific antibodies to detect phosphorylation of
      cytoplasmic signaling molecules. The effect of ZD1839 on growth of these breast
      cells was assessed with anchorage-dependent and anchorage-independent growth
      assays. Its effect on ER-negative mammary tumorigenesis was assessed in MMTV
      erbB2 transgenic mice. All statistical tests were two-sided. RESULTS: ZD1839
      suppressed the phosphorylation of EGFR and mitogen-activated protein kinase in
      normal and malignant breast cells. ZD1839 treatment statistically significantly
      suppressed mammary tumorigenesis in MMTV-erbB2 transgenic mice; median time to
      tumor development was approximately 230 days in vehicle-treated mice and more
      than 310 days in mice treated with ZD1839 at 100 mg/kg (P<.001). ZD1839 reduced
      proliferation of normal breast cells by 20.3% (95% confidence interval [CI] = 
      13.7% to 44.2%) and of tumor cells by 42.0% (95% CI = 20.2% to 58.2%). ZD1839
      also increased expression of the cell cycle regulator p27 in normal mammary
      tissue by 48.7% (95% CI = 27.0% to 74.2%) and in tumor tissue by 50.3% (95% CI =
      35.8% to 66.7%). CONCLUSION: This study appears to provide the preclinical
      rationale for the development of these EGFR tyrosine kinase inhibitors for the
      prevention of human breast cancer.

PMID- 14679153
TI  - Adjuvant chemotherapy followed by goserelin versus either modality alone for
      premenopausal lymph node-negative breast cancer: a randomized trial.
AB  - BACKGROUND: Although chemotherapy and ovarian function suppression are both
      effective adjuvant therapies for patients with early-stage breast cancer, little
      is known of the efficacy of their sequential combination. In an International
      Breast Cancer Study Group (IBCSG) randomized clinical trial (Trial VIII) for pre-
      and perimenopausal women with lymph node-negative breast cancer, we compared
      sequential chemotherapy followed by the gonadotropin-releasing hormone agonist
      goserelin with each modality alone. METHODS: From March 1990 through October
      1999, 1063 patients stratified by estrogen receptor (ER) status and radiotherapy
      plan were randomly assigned to receive goserelin for 24 months (n = 346), six
      courses of "classical" CMF (cyclophosphamide, methotrexate, 5-fluorouracil)
      chemotherapy (n = 360), or six courses of classical CMF followed by 18 months of
      goserelin (CMF --> goserelin; n = 357). A fourth arm (no adjuvant treatment) with
      46 patients was discontinued in 1992. Tumors were classified as ER-negative
      (30%), ER-positive (68%), or ER status unknown (3%). Twenty percent of patients
      were aged 39 years or younger. The median follow-up was 7 years. The primary
      outcome was disease-free survival (DFS). RESULTS: Patients with ER-negative
      tumors achieved better disease-free survival if they received CMF (5-year DFS for
      CMF = 84%, 95% confidence interval [CI] = 77% to 91%; 5-year DFS for CMF -->
      goserelin = 88%, 95% CI = 82% to 94%) than if they received goserelin alone (5
      year DFS = 73%, 95% CI = 64% to 81%). By contrast, for patients with ER-positive
      disease, chemotherapy alone and goserelin alone provided similar outcomes (5-year
      DFS for both treatment groups = 81%, 95% CI = 76% to 87%), whereas sequential
      therapy (5-year DFS = 86%, 95% CI = 82% to 91%) provided a statistically
      nonsignificant improvement compared with either modality alone, primarily because
      of the results among younger women. CONCLUSIONS: Premenopausal women with ER
      negative (i.e., endocrine nonresponsive), lymph node-negative breast cancer
      should receive adjuvant chemotherapy. For patients with ER-positive (i.e.,
      endocrine responsive) disease, the combination of chemotherapy with ovarian
      function suppression or other endocrine agents, and the use of endocrine therapy
      alone should be studied.

PMID- 14679154
TI  - Interaction of retroviral Tax oncoproteins with tristetraprolin and regulation of
      tumor necrosis factor-alpha expression.
AB  - BACKGROUND: The Tax oncoproteins are transcriptional regulators of viral
      expression involved in pathogenesis induced by complex leukemogenic retroviruses
      (or delta-retroviruses, i.e., primate T-cell leukemia viruses and bovine leukemia
      virus). To better understand the molecular pathways leading to cell
      transformation, we aimed to identify cellular proteins interacting with Tax.
      METHODS: We used a yeast two-hybrid system to identify interacting cellular
      proteins. Interactions between Tax and candidate interacting cellular proteins
      were confirmed by glutathione S-transferase (GST) pulldown assays, co
      immunoprecipitation, and confocal microscopy. Functional interactions between Tax
      and one interacting protein, tristetraprolin (TTP), were assessed by analyzing
      the expression of tumor necrosis factor-alpha (TNF-alpha), which is regulated by
      TTP, in mammalian cells (HeLa, D17, HEK 293, and RAW 264.7) transiently
      transfected with combinations of intact and mutant Tax and TTP. RESULTS: We
      obtained seven interacting cellular proteins, of which one, TTP, was further
      characterized. Tax and TTP were found to interact specifically through their
      respective carboxyl-terminal domains. The proteins colocalized in the cytoplasm
      in a region surrounding the nucleus of HeLa cells. Furthermore, coexpression of
      Tax was associated with nuclear accumulation of TTP. TTP is an immediate-early
      protein that inhibits expression of TNF-alpha at the post-transcriptional level.
      Expression of Tax reverted this inhibition, both in transient transfection
      experiments and in stably transfected macrophage cell lines. CONCLUSION: Tax,
      through its interactions with the TTP repressor, indirectly increases TNF-alpha
      expression. This observation is of importance for the cell transformation process
      induced by leukemogenic retroviruses, because TNF-alpha overexpression plays a
      central role in pathogenesis.

PMID- 14679155
TI  - Cell cycle checkpoint function in bladder cancer.
AB  - BACKGROUND: Cell cycle checkpoints function to maintain genetic stability by
      providing additional time for repair of DNA damage and completion of events that
      are necessary for accurate cell division. Some checkpoints, such as the DNA
      damage G1 checkpoint, are dependent on p53, whereas other checkpoints, such as
      the decatenation G(2) checkpoint, are not. Because bladder transitional cell
      carcinomas (TCCs) often contain numerous chromosomal aberrations and appear to
      have highly unstable genomes, we analyzed cell cycle checkpoint functions in a
      panel of TCC lines. METHODS: Cell cycle arrest was induced in normal human
      fibroblasts (NHF1-hTERT) and normal human uroepithelial cells (HUCs), and TCC
      lines and checkpoint functions were quantified using flow cytometry and
      fluorescence microscopy. The inducers and checkpoints were ionizing radiation
      (i.e., DNA damage) (G1 and G2 checkpoints), the mitotic inhibitor colcemid
      (polyploidy checkpoint), or the topoisomerase II catalytic inhibitor ICRF-193
      (decatenation G2 checkpoint). Four of the five TCC lines expressed mutant p53.
      RESULTS: HUCs had an effective G1 checkpoint response to ionizing radiation, with
      68% of cells inhibited from moving from G1 into S phase. By contrast, G1
      checkpoint function was severely attenuated (<15% inhibition) in three of the
      five TCC lines and moderately attenuated (<50% inhibition) in the other two
      lines. NHF1-hTERT had an effective polyploidy checkpoint response, but three of
      five TCC lines were defective in this checkpoint. HUCs had effective ionizing
      radiation and decatenation G2 checkpoint responses. All TCC lines had a
      relatively effective G2 checkpoint response to DNA damage, although the responses
      of two of the TCC lines were moderately attenuated relative to HUCs. All TCC
      lines had a severe defect in the decatenation G2 checkpoint response. CONCLUSION:
      Bladder TCC lines have defective cell cycle checkpoint functions, suggesting that
      the p53-independent decatenation G2 checkpoint may cooperate with the p53
      dependent G1 checkpoints to preserve chromosomal stability and suppress bladder
      carcinogenesis.

PMID- 14679156
TI  - Randomized controlled trial of once- versus thrice-daily tobramycin in febrile
      neutropenic children undergoing stem cell transplantation.
AB  - BACKGROUND: The benefits of aminoglycoside antibiotics, such as tobramycin,
      administered as a once-daily dose to manage febrile neutropenia, have been
      demonstrated in many patient populations. However, toxicity and safety data are
      lacking for pediatric stem cell transplant recipients, who are at especially high
      risk for aminoglycoside-related toxicity and infectious morbidity. In particular,
      the relative nephrotoxicity and efficacy of tobramycin administered as a single
      daily dose or as three daily doses among this patient population is not known.
      METHODS: We conducted a randomized, double-blind controlled study of tobramycin
      dosing among children 18 years or younger who had fever and neutropenia while
      undergoing stem cell transplantation. From October 2000 through November 2002, 60
      children were randomly assigned to receive intravenous tobramycin, as either a
      single daily dose (n = 29) or every 8 hours (n = 31), in combination with either
      piperacillin or ceftazidime (intravenous). Tobramycin doses were adjusted to
      achieve pharmacokinetic targets. The primary outcome was nephrotoxicity, as
      represented by the maximal percent increase in serum creatinine concentration
      throughout the episode of febrile neutropenia relative to the baseline serum
      creatinine concentration. Efficacy was a secondary outcome and was defined as
      survival of the episode without modification of the antibacterial regimen. All
      statistical tests were two-sided. RESULTS: In a modified intent-to-treat
      analysis, the mean maximal percent increase in serum creatinine concentration was
      32% (N = 26) in the once daily dose group and 51% (N = 28) in the every 8 hours
      dose group (difference = 19%, 95% confidence interval [CI] = 0% to 38%; P =.054).
      Among patients evaluable for efficacy, 12 (46%) of 26 patients in the once daily
      dose group and five (19%) of 27 patients in the every 8 hours dose group survived
      the episode of febrile neutropenia without requiring antibacterial treatment
      modification (difference = 27%, 95% CI = 4% to 52%; P =.03). There was one death
      in each group. CONCLUSIONS: In febrile neutropenic children undergoing stem cell
      transplantation, tobramycin may be less nephrotoxic and more efficacious when
      administered as a once daily dose than when administered every 8 hours.

PMID- 14679157
TI  - Determinants of BRAF mutations in primary melanomas.
AB  - The RAS/mitogen-activated protein kinase pathway sends external growth-promoting
      signals to the nucleus. BRAF, a critical serine/threonine kinase in this pathway,
      is frequently activated by somatic mutation in melanoma. Using a cohort of 115
      patients with primary invasive melanomas, we show that BRAF mutations are
      statistically significantly more common in melanomas occurring on skin subject to
      intermittent sun exposure than elsewhere (23 of 43 patients; P<.001, two-sided
      Fisher's exact test). By contrast, BRAF mutations in melanomas on chronically sun
      damaged skin (1 of 12 patients) and melanomas on skin relatively or completely
      unexposed to sun, such as palms, soles, subungual sites (6 of 39 patients), and
      mucosal membranes (2 of 21 patients) are rare. We found no association of
      mutation status with clinical outcome or with the presence of an associated
      melanocytic nevus. The mutated BRAF allele was frequently found at an elevated
      copy number, implicating BRAF as one of the factors driving selection for the
      frequent copy number increases of chromosome 7q in melanoma. In summary, the
      uneven distribution of BRAF mutations strongly suggests distinct genetic pathways
      leading to melanoma. The high mutation frequency in melanomas arising on
      intermittently sun-exposed skin suggests a complex causative role of such
      exposure that mandates further evaluation.

PMID- 14679159
TI  - Re: Soy, isoflavones, and breast cancer risk in Japan.

PMID- 14679161
TI  - Microwave-mediated analysis for sugar, fatty acid, and sphingoid compositions of
      glycosphingolipids.
AB  - For chemical characterization of glycosphingolipids, it is necessary to determine
      the chemical compositions of three constituents, i.e., sugars, fatty acids, and
      sphingoids. A new rapid analytical method is described using a one-pot reaction
      in a household microwave oven, producing sugars, fatty acids, and especially
      sphingoids free of by-products, from a single aliquot of a biological sample.
      Glycosphingolipids were hydrolyzed by microwave exposure with 0.1 M NaOH/CH(3)OH
      for 2 min followed by 1 M HCl/CH(3)OH for 45 s. The alkaline methanolysis step
      produced intermediate lysoglycosphingolipids virtually free of by-products such
      as the O-methyl ethers usually seen. The fatty acid methyl esters were extracted
      with n-hexane, and other reaction products were dried, taken up in aqueous
      alkaline methanol, and shaken with chloroform. Sphingoids partitioned into the
      organic phase under these conditions, whereas the sugar portion that partitioned
      into the aqueous phase was re-N-acetylated and remethanolyzed for 30 s by
      microwave exposure. Analysis of the profiles of glycosphingolipid constituents
      obtained using the microwave oven method showed that they were quantitatively and
      qualitatively comparable to those obtained by time-consuming conventional
      methods, which require reaction for several hours. Analysis of the three
      constituents, including analysis by gas chromatography, may be obtained within 1
      day using the method described here.

PMID- 14679163
TI  - Lipid transfer particle mediates the delivery of diacylglycerol from lipophorin
      to fat body in larval Manduca sexta.
AB  - This work analyzed the process of lipid storage in fat body of larval Manduca
      sexta, focusing on the role of lipid transfer particle (LTP). Incubation of fat
      bodies with [(3)H]diacylglycerol-labeled lipophorin resulted in a significant
      accumulation of diacylglycerol (DAG) and triacylglycerol (TAG) in the tissue.
      Transfer of DAG to fat body and its storage as TAG was significantly inhibited
      (60%) by preincubating the tissue with anti-LTP antibody. Lipid transfer was
      restored to control values by adding LTP to fat body. Incubation of fat body with
      dual-labeled DAG lipophorin or its treatment with ammonium chloride showed that
      neither a membrane-bound lipoprotein lipase nor lipophorin endocytosis is a
      relevant pathway to transfer or to storage lipids into fat body, respectively.
      Treatment of fat body with suramin caused a 50% inhibition in [(3)H]DAG transfer
      from lipophorin. Treatment of [(3)H]DAG-labeled fat body with lipase
      significantly reduced the amount of [(3)H]DAG associated with the tissue,
      suggesting that the lipid is still on the external surface of the membrane.
      Whether this lipid represents irreversibly adsorbed lipophorin or a DAG lipase
      sensitive pool is unknown. Nevertheless, these results indicate that the main
      pathway for DAG transfer from lipophorin to fat body is via LTP and receptor
      mediated processes.

PMID- 14679164
TI  - A comparison of the metabolism of eighteen-carbon 13C-unsaturated fatty acids in
      healthy women.
AB  - Altered use of different dietary fatty acids may contribute to several chronic
      diseases, including obesity, noninsulin-dependent diabetes mellitus, and
      cardiovascular disease. However, few comparative data are available to support
      this link, so the goal of the present study was to compare the metabolism of
      [(13)C]oleate, [(13)C]alpha-linolenate, [(13)C]elaidate, and [(13)C]linoleate
      through oxidation and incorporation into plasma lipid fractions and adipose
      tissue. Each tracer was given as a single oral bolus to six healthy women.
      Samples were collected over 8 days, and (13)C was analyzed using isotope ratio
      mass spectrometry. At 9 h postdose, cumulative oxidation was similar for
      [(13)C]elaidate, [(13)C]oleate, and [(13)C]alpha-linolenate (19 +/- 1%, 20 +/-
      4%, and 19 +/- 3% dose, respectively). Significantly lower oxidation of
      [(13)C]linoleate (12 +/- 4% dose; P < 0.05) was accompanied by its higher
      incorporation into plasma phospholipids and cholesteryl esters. Abdominal adipose
      tissue was enriched with [(13)C]alpha-linolenate, [(13)C]elaidate, or
      [(13)C]linoleate within 6 h. The percentage linoleate in plasma phospholipids
      correlated positively with [(13)C]linoleate and [(13)C]elaidate oxidation,
      indicating a potential role of background diet. Conversion of [(13)C]linoleate
      and [(13)C]alpha-linolenate to longer chain polyunsaturates was a quantitatively
      minor route of utilization.

PMID- 14679165
TI  - Genome-wide linkage scan reveals multiple susceptibility loci influencing lipid
      and lipoprotein levels in the Quebec Family Study.
AB  - A genome-wide linkage study was performed to identify chromosomal regions
      harboring genes influencing lipid and lipoprotein levels. Linkage analyses were
      conducted for four quantitative lipoprotein/lipid traits, i.e., total
      cholesterol, triglyceride, HDL-cholesterol (HDL-C), and LDL-C concentrations, in
      930 subjects enrolled in the Quebec Family Study. A maximum of 534 pairs of
      siblings from 292 nuclear families were available. Linkage was tested using both
      allele-sharing and variance-component linkage methods. The strongest evidence of
      linkage was found on chromosome 12q14.1 at marker D12S334 for HDL-C, with a
      logarithm of the odds (LOD) score of 4.06. Chromosomal regions harboring
      quantitative trait loci (QTLs) for LDL-C included 1q43 (LOD = 2.50), 11q23.2 (LOD
      = 3.22), 15q26.1 (LOD = 3.11), and 19q13.32 (LOD = 3.59). In the case of
      triglycerides, three markers located on 2p14, 11p13, and 11q24.1 provided
      suggestive evidence of linkage (LOD > 1.75). Tests for total cholesterol levels
      yielded significant evidence of linkage at 15q26.1 and 18q22.3 with the allele
      sharing linkage method, but the results were nonsignificant with the variance
      component method. In conclusion, this genome scan provides evidence for several
      QTLs influencing lipid and lipoprotein levels. Promising candidate genes were
      located in the vicinity of the genomic regions showing evidence of linkage.

PMID- 14679166
TI  - Cholesteryl ester transfer protein modulates the effect of liver X receptor
      agonists on cholesterol transport and excretion in the mouse.
AB  - Human plasma, unlike mouse plasma, contains the cholesteryl ester transfer
      protein (CETP) that may influence the reverse cholesterol transport. Liver X
      receptor (LXR), an oxysterol-activated nuclear receptor induces CETP
      transcription via a direct repeat 4 element in the CETP gene promoter. The aim of
      the study was to assess in vivo the impact of LXR activation on CETP expression
      and its consequences on plasma lipid metabolism and hepatic and bile lipid
      content. Wild-type and humanized mice expressing CETP were treated for five days
      with T0901317 LXR agonist. This treatment produced marked rises in both hepatic
      CETP mRNA and plasma CETP activity levels. Interestingly, the LXR agonist
      mediated, 2-fold rise in both total and HDL cholesterol levels in treated wild
      type mice was not observed in CETPTg mice, and the accumulation of cholesterol in
      the liver of CETPTg mice was reversed by LXR agonist treatment. Moreover, LXR
      activation induced a 2-fold increase in hepatic LDL-receptor expression in wild
      type and CETPTg mice, and it produced a significantly greater rise in biliary
      cholesterol concentration in CETPTg mice as compared with wild-type mice. In
      conclusion, induction of CETP constitutes a major determinant of the effect of
      LXR agonists on cholesterol transport and excretion.

PMID- 14679167
TI  - Different transport routes for high density lipoprotein and its associated free
      sterol in polarized hepatic cells.
AB  - We analyzed the intracellular transport of HDL and its associated free sterol in
      polarized human hepatoma HepG2 cells. Using pulse-chase protocols, we
      demonstrated that HDL labeled with Alexa 488 at the apolipoprotein (Alexa 488
      HDL) was internalized by a scavenger receptor class B type I (SR-BI)-dependent
      process at the basolateral membrane and became enriched in a subapical/apical
      recycling compartment. Most Alexa 488-HDL was rapidly recycled to the basolateral
      cell surface and released from cells. Within 30 min of chase at 37 degrees C,
      approximately 3% of the initial cell-associated Alexa 488-HDL accumulated in the
      biliary canaliculus (BC) formed at the apical pole of polarized HepG2 cells. Even
      less Alexa 488-HDL was transported to late endosomes or lysosomes. The
      fluorescent cholesterol analog dehydroergosterol (DHE) incorporated into Alexa
      488-HDL was delivered to the BC within a few minutes, independent of the labeled
      apolipoprotein. This transport did not require metabolic energy and could be
      blocked by antibodies against SR-BI. The fraction of cell-associated DHE
      transported to the BC was comparable when cells were incubated with either Alexa
      488-HDL containing DHE or with DHE bound to methyl-beta-cyclodextrin. We conclude
      that rapid, nonvesicular transport of sterol to the BC and efficient recycling of
      HDL particles underlies the selective sorting of sterol from HDLs in hepatocytes.

PMID- 14679168
TI  - The bridging function of hepatic lipase clears plasma cholesterol in LDL receptor
      deficient "apoB-48-only" and "apoB-100-only" mice.
AB  - Hepatic lipase clears plasma cholesterol by lipolytic and nonlipolytic processing
      of lipoproteins. We hypothesized that the nonlipolytic processing (known as the
      bridging function) clears cholesterol by removing apoB-48- and apoB-100
      containing lipoproteins by whole particle uptake. To test our hypotheses, we
      expressed catalytically inactive human HL (ciHL) in LDL receptor deficient "apoB
      48-only" and "apoB-100-only" mice. Expression of ciHL in "apoB-48-only" mice
      reduced cholesterol by reducing LDL-C (by 54%, 46 +/- 6 vs. 19 +/- 8 mg/dl, P <
      0.001). ApoB-48 was similarly reduced (by 60%). The similar reductions in LDL-C
      and apoB-48 indicate cholesterol removal by whole particle uptake. Expression of
      ciHL in "apoB-100-only" mice reduced cholesterol by reducing IDL-C (by 37%, 61 +/
      19 vs. 38 +/- 12 mg/dl, P < 0.003). Apo-B100 was also reduced (by 27%). The
      contribution of nutritional influences was examined with a high-fat diet
      challenge in the "apoB-100-only" background. On the high fat diet, ciHL reduced
      IDL-C (by 30%, 355 +/- 72 vs. 257 +/- 64 mg/dl, P < 0.04) but did not reduce apoB
      100. The reduction in IDL-C in excess of apoB-100 suggests removal either by
      selective cholesteryl ester uptake, or by selective removal of larger,
      cholesteryl ester-enriched particles. Our results demonstrate that the bridging
      function removes apoB-48- and apoB-100-containing lipoproteins by whole particle
      uptake and other mechanisms.

PMID- 14679169
TI  - Icelandic history drives genetic future.

PMID- 14679172
TI  - Obesity-induced inflammatory changes in adipose tissue.
AB  - Obesity is associated with a state of chronic, low-grade inflammation. Two
      manuscripts in this issue of the JCI (see the related articles beginning on pages
      1796 and 1821) now report that obese adipose tissue is characterized by
      macrophage infiltration and that these macrophages are an important source of
      inflammation in this tissue. These studies prompt consideration of new models to
      include a major role for macrophages in the molecular changes that occur in
      adipose tissue in obesity.

PMID- 14679173
TI  - A radical explanation for glucose-induced beta cell dysfunction.
AB  - The development of type 2 diabetes requires impaired beta cell function.
      Hyperglycemia itself causes further decreases in glucose-stimulated insulin
      secretion. A new study demonstrates that hyperglycemia-induced mitochondrial
      superoxide production activates uncoupling protein 2, which decreases the ATP/ADP
      ratio and thus reduces the insulin-secretory response. These data suggest that
      pharmacologic inhibition of mitochondrial superoxide overproduction in beta cells
      exposed to hyperglycemia could prevent a positive feed-forward loop of
      glucotoxicity that drives impaired glucose tolerance toward frank type 2
      diabetes.

PMID- 14679171
TI  - Epithelial-mesenchymal transition and its implications for fibrosis.
AB  - Epithelial to mesenchymal transition (EMT) is a central mechanism for
      diversifying the cells found in complex tissues. This dynamic process helps
      organize the formation of the body plan, and while EMT is well studied in the
      context of embryonic development, it also plays a role in the genesis of
      fibroblasts during organ fibrosis in adult tissues. Emerging evidence from
      studies of renal fibrosis suggests that more than a third of all disease-related
      fibroblasts originate from tubular epithelia at the site of injury. This review
      highlights recent advances in the process of EMT signaling in health and disease
      and how it may be attenuated or reversed by selective cytokines and growth
      factors.

PMID- 14679174
TI  - It takes two to tango: mast cell and Schwann cell interactions in neurofibromas.
AB  - Neurofibromas are benign tumors comprised primarily of Schwann cells and
      fibroblasts. Mast cell infiltration is a well-known phenomenon; however, their
      role in tumor pathogenesis has been enigmatic. In an elegant set of experiments
      using cells derived from a murine model of neurofibromatosis 1 (NF1), Yang et al.
      dissect the molecular pathways involved in mast cell migration to neurofibromin
      deficient Schwann cells. These results set the stage for rational development of
      therapeutics that could influence the multicellular microenvironment of
      neurofibromas to inhibit the development and/or progression of these tumors in
      human NF1.

PMID- 14679175
TI  - Tumbling down a different pathway to genetic instability.
AB  - Ulcerative colitis (UC), a chronic inflammatory condition associated with a
      predisposition to colon cancer, is frequently characterized by DNA damage in the
      form of microsatellite instability (MSI). A new report links inflammation in UC
      with increases in the DNA repair enzymes 3-methyladenine DNA glycosylase and
      apurinic/apyrimidinic endonuclease, and, paradoxically, with increased MSI. These
      findings may represent a novel mechanism contributing to MSI in chronic
      inflammation.

PMID- 14679177
TI  - Chronic inflammation in fat plays a crucial role in the development of obesity
      related insulin resistance.
AB  - Insulin resistance arises from the inability of insulin to act normally in
      regulating nutrient metabolism in peripheral tissues. Increasing evidence from
      human population studies and animal research has established correlative as well
      as causative links between chronic inflammation and insulin resistance. However,
      the underlying molecular pathways are largely unknown. In this report, we show
      that many inflammation and macrophage-specific genes are dramatically upregulated
      in white adipose tissue (WAT) in mouse models of genetic and high-fat diet
      induced obesity (DIO). The upregulation is progressively increased in WAT of mice
      with DIO and precedes a dramatic increase in circulating-insulin level. Upon
      treatment with rosiglitazone, an insulin-sensitizing drug, these macrophage
      originated genes are downregulated. Histologically, there is evidence of
      significant infiltration of macrophages, but not neutrophils and lymphocytes,
      into WAT of obese mice, with signs of adipocyte lipolysis and formation of
      multinucleate giant cells. These data suggest that macrophages in WAT play an
      active role in morbid obesity and that macrophage-related inflammatory activities
      may contribute to the pathogenesis of obesity-induced insulin resistance. We
      propose that obesity-related insulin resistance is, at least in part, a chronic
      inflammatory disease initiated in adipose tissue.

PMID- 14679176
TI  - Obesity is associated with macrophage accumulation in adipose tissue.
AB  - Obesity alters adipose tissue metabolic and endocrine function and leads to an
      increased release of fatty acids, hormones, and proinflammatory molecules that
      contribute to obesity associated complications. To further characterize the
      changes that occur in adipose tissue with increasing adiposity, we profiled
      transcript expression in perigonadal adipose tissue from groups of mice in which
      adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay)
      and obese (Lepob). We found that the expression of 1,304 transcripts correlated
      significantly with body mass. Of the 100 most significantly correlated genes, 30%
      encoded proteins that are characteristic of macrophages and are positively
      correlated with body mass. Immunohistochemical analysis of perigonadal,
      perirenal, mesenteric, and subcutaneous adipose tissue revealed that the
      percentage of cells expressing the macrophage marker F4/80 (F4/80+) was
      significantly and positively correlated with both adipocyte size and body mass.
      Similar relationships were found in human subcutaneous adipose tissue stained for
      the macrophage antigen CD68. Bone marrow transplant studies and quantitation of
      macrophage number in adipose tissue from macrophage-deficient (Csf1op/op) mice
      suggest that these F4/80+ cells are CSF-1 dependent, bone marrow-derived adipose
      tissue macrophages. Expression analysis of macrophage and nonmacrophage cell
      populations isolated from adipose tissue demonstrates that adipose tissue
      macrophages are responsible for almost all adipose tissue TNF-alpha expression
      and significant amounts of iNOS and IL-6 expression. Adipose tissue macrophage
      numbers increase in obesity and participate in inflammatory pathways that are
      activated in adipose tissues of obese individuals.

PMID- 14679178
TI  - Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta
      cell dysfunction.
AB  - Failure to secrete adequate amounts of insulin in response to increasing
      concentrations of glucose is an important feature of type 2 diabetes. The
      mechanism for loss of glucose responsiveness is unknown. Uncoupling protein 2
      (UCP2), by virtue of its mitochondrial proton leak activity and consequent
      negative effect on ATP production, impairs glucose-stimulated insulin secretion.
      Of interest, it has recently been shown that superoxide, when added to isolated
      mitochondria, activates UCP2-mediated proton leak. Since obesity and chronic
      hyperglycemia increase mitochondrial superoxide production, as well as UCP2
      expression in pancreatic beta cells, a superoxide-UCP2 pathway could contribute
      importantly to obesity- and hyperglycemia-induced beta cell dysfunction. This
      study demonstrates that endogenously produced mitochondrial superoxide activates
      UCP2-mediated proton leak, thus lowering ATP levels and impairing glucose
      stimulated insulin secretion. Furthermore, hyperglycemia- and obesity-induced
      loss of glucose responsiveness is prevented by reduction of mitochondrial
      superoxide production or gene knockout of UCP2. Importantly, reduction of
      superoxide has no beneficial effect in the absence of UCP2, and superoxide levels
      are increased further in the absence of UCP2, demonstrating that the adverse
      effects of superoxide on beta cell glucose sensing are caused by activation of
      UCP2. Therefore, superoxide-mediated activation of UCP2 could play an important
      role in the pathogenesis of beta cell dysfunction and type 2 diabetes.

PMID- 14679179
TI  - Auricular chondritis in NOD.DQ8.Abetao (Ag7-/-) transgenic mice resembles human
      relapsing polychondritis.
AB  - Relapsing polychondritis is a multisystem autoimmune disease involving cartilage
      destruction but no known causative antigen. HLA-DQ8 has been associated with
      various autoimmune diseases in humans. To study the role of DQ8 in autoimmune
      diseases, we have generated transgenic mice expressing DQ8 (DQA1*0301, DQB1*0302)
      in a NOD background lacking endogenous class II molecules (Abetao). Upon
      immunization with type II collagen (CII), 85% of NOD.DQ8 mice develop severe
      experimental polychondritis, auricular chondritis, and polyarthritis, with
      clinical and histological similarities to relapsing polychondritis (RP) in
      humans. CII-immunized mice mount a T cell response and produce Ab's to type IX
      collagen (CIX) and self-CII. Transgene-negative littermates do not develop any
      serological and clinical manifestations following immunization. B10.DQ8
      transgenic mice develop polyarthritis and Ab's to CII only. The susceptibility to
      auricular chondritis in NOD.DQ8 mice can be attributed to response to CIX. A
      higher number of activated cells, CD4+CD44(hi)CD62L(lo), and lower regulatory
      cells CD4+CD152+CD25+ were observed in NOD.DQ8 mice compared with B10.DQ8 mice.
      The NOD.DQ8 mice provide a model of RP with a high disease incidence and multiple
      organ involvement to investigate putative autoantigen and regulatory cells
      involved in disease pathogenesis. An experimental model restricted by the human
      class II molecule will be valuable when studying the role of various collagens in
      immunologic and pathologic responses in human RP.

PMID- 14679180
TI  - Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for
      Nf1+/- mast cells.
AB  - The NF1 tumor suppressor gene encodes a GTPase-activating protein called
      neurofibromin that negatively regulates Ras signaling. Mutations in NF1 cause
      neurofibromatosis type 1 (NF1). The development of neurofibromas, which are
      complex tumors composed of multiple cell types, is a hallmark of NF1. Somatic
      inactivation of murine Nf1 in Schwann cells is necessary, but not sufficient, to
      initiate neurofibroma formation. Neurofibromas occur with high penetrance in mice
      in which Nf1 is ablated in Schwann cells in the context of a heterozygous mutant
      (Nf1+/-) microenvironment. Mast cells infiltrate neurofibromas, where they
      secrete proteins that can remodel the ECM and initiate angiogenesis. Thus,
      identification of mechanisms responsible for mast cell migration to tumor
      microenvironments is important for understanding tumorigenesis and for designing
      potential therapies. Here, we show that homozygous Nf1 mutant (Nf1-/-) Schwann
      cells secrete Kit ligand (KitL), which stimulates mast cell migration, and that
      Nf1+/- mast cells are hypermotile in response to KitL. Furthermore, we link
      hyperactivation of the Ras-class IA-PI3K-Rac2 pathway to increased Nf1+/- mast
      cell migration. Thus, these studies identify a novel interaction between Nf1-/-
      Schwann cells and Nf1+/- mast cells that is likely to be important in
      neurofibroma formation.

PMID- 14679181
TI  - Chemokine-mediated recruitment of NK cells is a critical host defense mechanism
      in invasive aspergillosis.
AB  - Invasive aspergillosis is a severe pneumonia that is usually fatal despite
      currently available therapy. The disease disproportionately afflicts
      immunocompromised patients, indicating the critical importance of the immune
      status of the host in this infection, but the defense mechanisms against this
      pathogen remain incompletely understood. In the current study, we hypothesized
      that the chemokine ligand monocyte chemotactic protein-1, also designated CC
      chemokine ligand-2 (MCP-1/CCL2) is necessary for effective host defense against
      invasive aspergillosis in immunocompromised hosts. We found a rapid and marked
      induction of MCP-1/CCL2 in the lungs of neutropenic mice with invasive
      aspergillosis. Neutralizing MCP-1/CCL2 resulted in twofold greater mortality and
      greater than threefold increase in pathogen burden in the lungs. Neutralization
      of MCP-1/CCL2 also resulted in reduced recruitment of NK cells to the lungs at
      early time points, but did not affect the number of other leukocyte effector
      cells in the lungs. Ab-mediated depletion of NK cells similarly resulted in
      impaired defenses against the infection, resulting in a greater than twofold
      increase in mortality and impaired clearance of the pathogen from the lungs.
      These data establish MCP-1/CCL2-mediated recruitment of NK cells to the lungs as
      a critical early host defense mechanism in invasive aspergillosis and demonstrate
      NK cells to be an important and previously unrecognized effector cell in this
      infection.

PMID- 14679182
TI  - Pivotal role of Cu,Zn-superoxide dismutase in endothelium-dependent
      hyperpolarization.
AB  - The endothelium plays an important role in maintaining vascular homeostasis by
      synthesizing and releasing several vasodilating factors, including prostacyclin,
      NO, and endothelium-derived hyperpolarizing factor (EDHF). We have recently
      identified that endothelium-derived H2O2 is an EDHF in mesenteric arteries of
      mice and humans and in porcine coronary microvessels. However, the mechanism for
      the endothelial production of H2O2 as an EDHF remains to be elucidated. In this
      study, we tested our hypothesis that Cu,Zn-superoxide dismutase (Cu,Zn-SOD) plays
      a pivotal role in endothelium-dependent hyperpolarization, using control and
      Cu,Zn-SOD-/- mice. In mesenteric arteries, EDHF-mediated relaxations and
      hyperpolarizations were significantly reduced in Cu,Zn-SOD-/- mice with no
      inhibitory effect of catalase, while endothelium-independent relaxations and
      hyperpolarizations were preserved. Endothelial H2O2 production also was
      significantly reduced in Cu,Zn-SOD-/- mice. In Langendorff isolated heart,
      bradykinin-induced increase in coronary flow was significantly reduced in Cu,Zn
      SOD-/- mice, again with no inhibitory effect of catalase. The exogenous SOD
      mimetic tempol significantly improved EDHF-mediated relaxations and
      hyperpolarizations and coronary flow response in Cu,Zn-SOD-/- mice. These results
      prove the novel concept that endothelial Cu,Zn-SOD plays an important role as an
      "EDHF synthase" in mice, in addition to its classical role to scavenge superoxide
      anions.

PMID- 14679183
TI  - Importance of minor histocompatibility antigen expression by nonhematopoietic
      tissues in a CD4+ T cell-mediated graft-versus-host disease model.
AB  - Minor histocompatibility antigens with expression restricted to the recipient
      hematopoietic compartment represent prospective immunological targets for graft
      versus-leukemia therapy. It remains unclear, however, whether donor T cell
      recognition of these hematopoietically derived minor histocompatibility antigens
      will induce significant graft-versus-host disease (GVHD). Using established bone
      marrow irradiation chimeras across the multiple minor histocompatibility antigen
      disparate, C57BL/6-->BALB.B combination, we studied the occurrence of lethal GVHD
      mediated by CD4+ T cells in recipient mice expressing only hematopoietically
      derived alloantigens. Even substantial dosages of donor C57BL/6 CD4+ T cells were
      unable to elicit lethal GVHD when transplanted into [BALB.B-->C57BL/6] chimeras.
      Instead, chimeric mice displayed transient cachexia with reduced target-tissue
      injury over time, reflecting an early, limited, graft-versus-host response. On
      the other hand, the importance of minor histocompatibility antigens derived from
      nonhematopoietic tissues was demonstrated by the finding that [C57BL/6-->BALB.B]
      chimeric mice succumbed to C57BL/6 CD4+ T cell-mediated GVHD. These data suggest
      that severe acute CD4+ T cell-mediated GVHD across this minor histocompatibility
      antigen barrier depends on the expression of nonhematopoietically rather than
      hematopoietically derived alloantigens for maximal target-tissue infiltration and
      injury.

PMID- 14679184
TI  - The adaptive imbalance in base excision-repair enzymes generates microsatellite
      instability in chronic inflammation.
AB  - Chronic infection and associated inflammation are key contributors to human
      carcinogenesis. Ulcerative colitis (UC) is an oxyradical overload disease and is
      characterized by free radical stress and colon cancer proneness. Here we examined
      tissues from noncancerous colons of ulcerative colitis patients to determine (a)
      the activity of two base excision-repair enzymes, AAG, the major 3-methyladenine
      DNA glycosylase, and APE1, the major apurinic site endonuclease; and (b) the
      prevalence of microsatellite instability (MSI). AAG and APE1 were significantly
      increased in UC colon epithelium undergoing elevated inflammation and MSI was
      positively correlated with their imbalanced enzymatic activities. These latter
      results were supported by mechanistic studies using yeast and human cell models
      in which overexpression of AAG and/or APE1 was associated with frameshift
      mutations and MSI. Our results are consistent with the hypothesis that the
      adaptive and imbalanced increase in AAG and APE1 is a novel mechanism
      contributing to MSI in patients with UC and may extend to chronic inflammatory or
      other diseases with MSI of unknown etiology.

PMID- 14679185
TI  - Physiological role for P2X1 receptors in renal microvascular autoregulatory
      behavior.
AB  - This study tests the hypothesis that P2X1 receptors mediate pressure-induced
      afferent arteriolar autoregulatory responses. Afferent arterioles from rats and
      P2X1 KO mice were examined using the juxtamedullary nephron technique. Arteriolar
      diameter was measured in response to step increases in renal perfusion pressure
      (RPP). Autoregulatory adjustments in diameter were measured before and during P2X
      receptor blockade with NF279 or A1 receptor blockade with 1,3-dipropyl-8
      cyclopentylxanthine (DPCPX). Acute papillectomy or furosemide perfusion was
      performed to interrupt distal tubular fluid flow past the macula densa, thus
      minimizing tubuloglomerular feedback-dependent influences on afferent arteriolar
      function. Under control conditions, arteriolar diameter decreased by 17% and 29%
      at RPP of 130 and 160 mmHg, respectively. Blockade of P2X1 receptors with NF279
      blocked pressure-mediated vasoconstriction, reflecting an attenuated
      autoregulatory response. The A1 receptor blocker DPCPX did not alter
      autoregulatory behavior or the response to ATP. Deletion of P2X1 receptors in KO
      mice significantly blunted autoregulatory responses induced by an increase in
      RPP, and this response was not further impaired by papillectomy or furosemide. WT
      control mice exhibited typical RPP-dependent vasoconstriction that was
      significantly attenuated by papillectomy. These data provide compelling new
      evidence indicating that tubuloglomerular feedback signals are coupled to
      autoregulatory preglomerular vasoconstriction through ATP-mediated activation of
      P2X1 receptors.

PMID- 14679186
TI  - Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking
      TRPV5.
AB  - Ca2+ ions play a fundamental role in many cellular processes, and the
      extracellular concentration of Ca2+ is kept under strict control to allow the
      proper physiological functions to take place. The kidney, small intestine, and
      bone determine the Ca2+ flux to the extracellular Ca2+ pool in a concerted
      fashion. Transient receptor potential (TRP) cation channel subfamily V, members 5
      and 6 (TRPV5 and TRPV6) have recently been postulated to be the molecular
      gatekeepers facilitating Ca2+ influx in these tissues and are members of the TRP
      family, which mediates diverse biological effects ranging from pain perception to
      male aggression. Genetic ablation of TRPV5 in the mouse allowed us to investigate
      the function of this novel Ca2+ channel in maintaining the Ca2+ balance. Here, we
      demonstrate that mice lacking TRPV5 display diminished active Ca2+ reabsorption
      despite enhanced vitamin D levels, causing severe hypercalciuria. In vivo
      micropuncture experiments demonstrated that Ca2+ reabsorption was malfunctioning
      within the early part of the distal convolution, exactly where TRPV5 is
      localized. In addition, compensatory hyperabsorption of dietary Ca2+ was measured
      in TRPV5 knockout mice. Furthermore, the knockout mice exhibited significant
      disturbances in bone structure, including reduced trabecular and cortical bone
      thickness. These data demonstrate the key function of TRPV5 in active Ca2+
      reabsorption and its essential role in the Ca2+ homeostasis.

PMID- 14679187
TI  - MinK, MiRP1, and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating.
AB  - High frequency firing in mammalian neurons requires ultra-rapid delayed rectifier
      potassium currents generated by homomeric or heteromeric assemblies of Kv3.1 and
      Kv3.2 potassium channel alpha subunits. Kv3.1 alpha subunits can also form slower
      activating channels by coassembling with MinK-related peptide 2 (MiRP2), a single
      transmembrane domain potassium channel ancillary subunit. Here, using channel
      subunits cloned from rat and expressed in Chinese hamster ovary cells, we show
      that modulation by MinK, MiRP1, and MiRP2 is a general mechanism for slowing of
      Kv3.1 and Kv3.2 channel activation and deactivation and acceleration of
      inactivation, creating a functionally diverse range of channel complexes. MiRP1
      also negatively shifts the voltage dependence of Kv3.1 and Kv3.2 channel
      activation. Furthermore, MinK, MiRP1, and MiRP2 each form channels with Kv3.1
      Kv3.2 heteromers that are kinetically distinct from one another and from
      MiRP/homomeric Kv3 channels. The findings illustrate a mechanism for dynamic
      expansion of the functional repertoire of Kv3.1 and Kv3.2 potassium currents and
      suggest roles for these alpha subunits outside the scope of sustained rapid
      neuronal firing.

PMID- 14679189
TI  - Nitrogen-regulated genes for the metabolism of cyanophycin, a bacterial nitrogen
      reserve polymer: expression and mutational analysis of two cyanophycin synthetase
      and cyanophycinase gene clusters in heterocyst-forming cyanobacterium Anabaena
      sp. PCC 7120.
AB  - Two gene clusters each encoding the cyanophycin-metabolism enzymes cyanophycin
      synthetase and cyanophycinase are found in the heterocyst-forming cyanobacterium
      Anabaena sp. PCC 7120. In cluster cph1, the genes cphB1 and cphA1 were expressed
      in media containing ammonium, nitrate, or N(2) as nitrogen sources, but
      expression was higher in the absence of combined nitrogen taking place both in
      vegetative cells and heterocysts. Both genes were cotranscribed from three
      putative promoters located upstream of cphB1, and, additionally, the cphA1 gene
      was expressed monocistronically from at least two promoters located in the
      intergenic cphB1-cphA1 region. Both constitutive promoters and promoters
      dependent on the global nitrogen control transcriptional regulator NtcA were
      identified. In cluster cph2, the cphB2 and cphA2 genes, which are found in
      opposite orientations, were expressed as monocistronic messages in media
      containing ammonium, nitrate, or N(2), but expression was higher in the absence
      of ammonium. Expression of the cph2 genes was lower than that of cph1 genes.
      Analysis of cph gene insertional mutants indicated that cluster cph1 genes
      contributed more than cluster cph2 genes to cyanophycin accumulation in the whole
      filament as well as in heterocysts. Diazotrophic growth was more severely
      impaired in cyanophycinase than in cyanophycin synthetase mutants, indicating
      that cyanophycin, although normally synthesized in the heterocysts, is not
      required for heterocyst function and that the inability to degrade this polymer
      is detrimental for the diazotrophic growth of the cyanobacterium.

PMID- 14679188
TI  - Hepatocyte growth factor regulates angiotensin converting enzyme expression.
AB  - Hepatocyte growth factor (HGF) is a mitogen, morphogen, and motogen that
      functions in tissue healing and acts as an anti-fibrotic factor. The mechanism
      for this is not well understood. Recent studies implicate somatic angiotensin
      converting enzyme (ACE) in fibrosis. We examined the effects of HGF on ACE
      expression in bovine pulmonary artery endothelial cells (BPAEC). Short term
      treatment of BPAEC with HGF transiently increased both ACE mRNA (3 h) and
      activity (24 h), as determined by ACE protease assays and reverse transcription
      PCR. Incubation of BPAEC with HGF for longer periods suppressed ACE mRNA (6 h)
      and activity (72 h). In contrast, phorbol ester (PMA) treatment produced
      sustained increase in ACE mRNA and activity. We examined the short term molecular
      effects of HGF on ACE using PMA for comparison. HGF and PMA increased
      transcription from a luciferase reporter with the core ACE promoter, which
      contains a composite binding site for SP1/3 and Egr-1. Immunocytochemistry and
      electrophoretic mobility shift assay showed that both HGF and PMA increased Egr-1
      binding. HGF also increased SP3 binding, as measured by EMSA. However, HGF and
      PMA increased the cellular activity of only Egr-1, not SP3, as measured by
      luciferase reporter assays. Deletion of the Egr-1 site in the reporter construct
      completely abrogated HGF-induced transcription but only approximately 50% of PMA
      induced activity. Expression of dominant negative Egr-1 and SP3 blocked up
      regulation of the ACE promoter by HGF but only reduced up-regulation by PMA.
      These results show that HGF transiently increases gene transcription of ACE via
      activation of Egr-1, whereas PMA regulation involves Egr-1 and additional
      factor(s).

PMID- 14679190
TI  - Plasmodium falciparum-activated chloride channels are defective in erythrocytes
      from cystic fibrosis patients.
AB  - An inwardly rectifying anion channel in malaria-infected red blood cells has been
      proposed to function as the "new permeation pathway" for parasite nutrient
      acquisition. As the channel shares several properties with the cystic fibrosis
      transmembrane conductance regulator (CFTR), we tested their interrelationship by
      whole-cell current measurements in Plasmodium falciparum-infected and uninfected
      red blood cells from control and cystic fibrosis (CF) patients. A CFTR-like
      linear chloride conductance as well as a malaria parasite-induced and a shrinkage
      activated endogenous inwardly rectifying chloride conductance with properties
      identical to the malaria-induced channel were all found to be defective in CF
      erythrocytes. Surprisingly, the absence of the inwardly rectifying chloride
      conductance in CF erythrocytes had no gross effect on in vitro parasite growth or
      new permeation pathway activity, supporting an argument against a close
      association between the Plasmodium-activated chloride channel and the new
      permeation pathway. The functional expression of CFTR in red blood cells opens
      new perspectives to exploit the erythrocyte as a readily available cell type in
      electrophysiological, diagnostic, and therapeutic studies of CF.

PMID- 14679191
TI  - An oriented peptide array library (OPAL) strategy to study protein-protein
      interactions.
AB  - One of the major questions in signal transduction is how the specificities of
      protein-protein interactions determine the assembly of distinct signaling
      complexes in response to stimuli. Several peptide library methods have been
      developed and widely used to study protein-protein interactions. These approaches
      primarily rely on peptide or DNA sequencing to identify the peptide or consensus
      motif for binding and may prove too costly or difficult to accommodate high
      throughput applications. We report here an oriented peptide array library (OPAL)
      approach that should facilitate high throughput proteomic analysis of protein
      protein interactions. OPAL integrates the principles of both the oriented peptide
      libraries and array technologies. Hundreds of pools of oriented peptide libraries
      are synthesized as amino acid scan arrays. We demonstrate that these arrays can
      be used to map the specificities of a variety of interactions, including
      antibodies, protein domains such Src homology 2 domains, and protein kinases.

PMID- 14679192
TI  - CD95-tyrosine nitration inhibits hyperosmotic and CD95 ligand-induced CD95
      activation in rat hepatocytes.
AB  - Epidermal growth factor receptor-dependent CD95-tyrosine phosphorylation was
      recently identified as an early step in apoptosis induction via the CD95 system
      (Reinehr, R., Schliess, F., and Haussinger, D. (2003) FASEB J. 17, 731-733). The
      effect of peroxynitrite (ONOO(-)) on modulation of the hyperosmotic and CD95
      ligand (CD95L)-induced CD95 activation process was studied. Pretreatment of
      hepatocytes with ONOO(-) inhibited CD95L- and hyperosmolarity-induced CD95
      membrane trafficking and formation of the death-inducing signaling complex, but
      not epidermal growth factor receptor activation and its association with CD95.
      Under these conditions, however, no tyrosine phosphorylation of CD95 occurred;
      instead, CD95 was tyrosine-nitrated. When ONOO(-) was added after induction of
      CD95-tyrosine phosphorylation by CD95L or hyperosmolarity, tyrosine nitration of
      CD95 was largely prevented and death-inducing signaling complex formation
      occurred. CD95-tyrosine nitration abolished the hyperosmotic sensitization of
      hepatocytes toward CD95L-induced apoptosis. Additionally, in CD95-yellow
      fluorescent protein-transfected Huh7-hepatoma cells, ONOO(-) induced CD95 Tyr
      nitration and prevented CD95L-induced Tyr phosphorylation and apoptosis. Tyrosine
      nitrated CD95 was also found in rat livers derived from an in vivo model of
      endotoxinemia. The data suggest that CD95-tyrosine nitration prevents CD95
      activation by inhibiting CD95-tyrosine phosphorylation. Apparently, CD95-tyrosine
      phosphorylation and nitration are mutually exclusive. The data identify critical
      tyrosine residues of CD95 as another target of the anti-apoptotic action of NO.

PMID- 14679193
TI  - Gln3 phosphorylation and intracellular localization in nutrient limitation and
      starvation differ from those generated by rapamycin inhibition of Tor1/2 in
      Saccharomyces cerevisiae.
AB  - The ability of the cell to sense environmental conditions and alter gene
      expression in response to them is critical to its survival. In Saccharomyces
      cerevisiae, the Tor1/2 serine/threonine kinases are global regulators situated at
      the top of a signal cascade reported to receive and transmit nutritional signals
      associated with the nitrogen supply of the cell. At the other end of that cascade
      is Gln3, one of two transcriptional activators responsible for most nitrogen
      catabolic gene expression. When nitrogen is in excess, Tor1/2 are active, and
      Gln3 is phosphorylated and localizes to the cytoplasm. If Tor1/2 are inhibited by
      rapamycin or mutation, Gln3 becomes dephosphorylated, accumulates in the nucleus,
      and mediates nitrogen catabolite repression (NCR)-sensitive transcription. The
      observations that Gln3 also accumulates in the nuclei of cells provided with poor
      nitrogen sources or during nitrogen starvation has led to the conclusion that
      Tor1/2 control intracellular Gln3 localization and NCR-sensitive transcription by
      regulating Gln3 phosphorylation/dephosphorylation. To test this model, we
      compared Gln3 phosphorylation states and intracellular localizations under a
      variety of physiological conditions known to elicit different levels of NCR
      sensitive transcription. Our data indicate that: (i) observable Gln3
      phosphorylation levels do not correlate in a consistent way with the quality or
      quantity of the nitrogen source provided, the intracellular localization of Gln3,
      or the capacity to support NCR-sensitive transcription. (ii) Gln3-Myc(13) is
      hyperphosphorylated during nitrogen and carbon starvation, but this uniform
      response does not correlate with Gln3 intracellular localization. (iii) Gln3
      Myc(13) dephosphorylation and nuclear localization correlate with one another at
      early but not late times after rapamycin treatment. These data suggest that
      rapamycin treatment and growth with poor nitrogen sources bring about nuclear
      accumulation of Gln3 but likely do so by different mechanisms or by a common
      mechanism involving molecules other than Gln3 and/or other than the levels of
      Gln3-Myc(13) phosphorylation thus far detected by others and ourselves.

PMID- 14679194
TI  - Hyaluronan structures synthesized by rat mesangial cells in response to
      hyperglycemia induce monocyte adhesion.
AB  - Mesangial expansion, the principal glomerular lesion in diabetic nephropathy, is
      preceded by a phenotypic activation and transient proliferation of the glomerular
      mesangial cells and by a prominent glomerular infiltration of monocytes and
      macrophages. Because this infiltration seems to play a key role in the subsequent
      mesangial matrix expansion, we tested the response of cultures of rat mesangial
      cells (RMCs) for monocyte adhesion in response to hyperglycemia. Increasing the
      medium glucose concentration from 5.6 mm (normal) to 25.6 mm (hyperglycemic)
      significantly increased hyaluronan in the cell matrix, with a concurrent 3- to 4
      fold increase in adhesion of U937 monocytic leukemic cells to cultures of near
      confluent RMCs. These responses were attributed directly to the high glucose
      concentration and not to increased extracellular osmolality. The monocytes
      primarily bind directly to hyaluronan-based structures in vitro. Abnormal
      deposits of hyaluronan were found in glomeruli of kidney sections from diabetic
      rats 1 week after streptozotocin treatment, often with closely associated
      monocytes/macrophages, suggesting that similar structures are relevant in vivo.
      The monocyte adhesion response to high glucose concentration required growth
      stimulation of RMCs by serum and activation of protein kinase C, and was
      inhibited by prior passage of the RMCs in the presence of heparin. These results
      suggest that the response may be cell growth state and protein kinase C
      dependent. When incubated with the viral mimetic, poly I:C, in the presence of
      normal glucose, heparin-passaged RMCs still increased cell-associated hyaluronan
      and exhibited hyaluronan-mediated adhesion of monocytes, indicating that the two
      stimuli, high glucose and viral mimetic, induce the production of the hyaluronan
      structures that promote monocyte adhesion by distinctly different intracellular
      signaling mechanisms.

PMID- 14679195
TI  - CzcR-CzcS, a two-component system involved in heavy metal and carbapenem
      resistance in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an environmental bacterium involved in mineralization
      of organic matter. It is also an opportunistic pathogen able to cause serious
      infections in immunocompromised hosts. As such, it is exposed to xenobiotics
      including solvents, heavy metals, and antimicrobials. We studied the response of
      P. aeruginosa upon exposure to heavy metals or antibiotics to investigate whether
      common regulatory mechanisms govern resistance to both types of compounds. We
      showed that sublethal zinc concentrations induced resistance to zinc, cadmium,
      and cobalt, while lethal zinc concentrations selected mutants constitutively
      resistant to these heavy metals. Both zinc-induced and stable zinc-resistant
      strains were also resistant to the carbapenem antibiotic imipenem. On the other
      hand, only 20% of clones selected on imipenem were also resistant to zinc. Heavy
      metal resistance in the mutants could be correlated by quantitative real time PCR
      with increased expression of the heavy metal efflux pump CzcCBA and its cognate
      two-component regulator genes czcR-czcS. Western blot analysis revealed reduced
      expression of the basic amino acid and carbapenem-specific OprD porin in all
      imipenem-resistant mutants. Sequencing of the czcR-czcS DNA region in eight
      independent zinc- and imipenem-resistant mutants revealed the presence of the
      same V194L mutation in the CzcS sensor protein. Overexpression in a susceptible
      wild type strain of the mutated CzsS protein, but not of the wild type form,
      resulted in decreased oprD and increased czcC expression. We further show that
      zinc is released from latex urinary catheters into urine in amounts sufficient to
      induce carbapenem resistance in P. aeruginosa, possibly compromising treatment of
      urinary tract infections by this class of antibiotics.

PMID- 14679196
TI  - Steroid hormones induce bcl-X gene expression through direct activation of distal
      promoter P4.
AB  - Bcl-X exists in at least five different isoforms with complex effects on
      programmed cell death. Glucocorticoids and progestins control bcl-X expression
      and influence the ratio between bcl-X(L) (antiapoptotic isoform) and bcl-X(S)
      (proapoptotic isoform) in different tissues. The 5'-UTR region of the mouse bcl-X
      gene contains at least five different promoters, which exhibit a tissue-specific
      pattern of promoter usage. Several mRNAs with different 5'-leading exons can be
      generated upon promoter activation. Here we explore the potential of the various
      bcl-X gene promoters to be regulated by glucocorticoids or progestins. We found
      that the region located immediately upstream of promoter 4 (P4) contains two
      hormone response element (HRE)-like sequences at positions -3040 (HRE I) and 
      3001 (HRE II) relative to the translation initiation codon. These HRE-like
      sequences confer hormone responsiveness to a core promoter and bind
      glucocorticoid or progesterone receptors in vitro. Point mutations of both HREs
      that prevent steroid receptor binding also eliminate hormonal inducibility. In
      cells treated with glucocorticoids, the hormone receptor is recruited to the P4
      region containing the HREs. Analysis of the products of the endogenous bcl-X in
      epithelial mammary cells showed that only transcripts originating from P4
      increased upon hormone treatment. This observation correlates with the induction
      of the bcl-X(L) mRNA, suggesting that P4 is one of the bcl-X promoters
      responsible for the generation of this antiapoptotic isoform.

PMID- 14679197
TI  - Residue Asp-189 controls both substrate binding and the monovalent cation
      specificity of thrombin.
AB  - Residue Asp-189 plays an important dual role in thrombin: it defines the primary
      specificity for Arg side chains and participates indirectly in the coordination
      of Na(+). The former role is shared by other proteases with trypsin-like
      specificity, whereas the latter is unique to Na(+)-activated proteases in blood
      coagulation and the complement system. Replacement of Asp-189 with Ala, Asn, Glu,
      and Ser drastically reduces the specificity toward substrates carrying Arg or Lys
      at P1, whereas it has little or no effect toward the hydrolysis of substrates
      carrying Phe at P1. These findings confirm the important role of Asp-189 in
      substrate recognition by trypsin-like proteases. The substitutions also affect
      significantly and unexpectedly the monovalent cation specificity of the enzyme.
      The Ala and Asn mutations abrogate monovalent cation binding, whereas the Ser and
      Glu mutations change the monovalent cation preference from Na(+) to the smaller
      cation Li(+) or to the larger cation Rb(+), respectively. The observation that a
      single amino acid substitution can alter the monovalent cation specificity of
      thrombin from Na(+) (Asp-189) to Li(+) (Ser-189) or Rb(+) (Glu-189) is
      unprecedented in the realm of monovalent cation-activated enzymes.

PMID- 14679198
TI  - Functional dissection of the transmembrane domains of the transporter associated
      with antigen processing (TAP).
AB  - The transporter associated with antigen processing (TAP1/2) translocates
      cytosolic peptides of proteasomal degradation into the endoplasmic reticulum (ER)
      lumen. A peptide-loading complex of tapasin, major histocompatibility complex
      class I, and several auxiliary factors is assembled at the transporter to
      optimize antigen display to cytotoxic T-lymphocytes at the cell surface. The
      heterodimeric TAP complex has unique N-terminal domains in addition to a 6 + 6
      transmembrane segment core common to most ABC transporters. Here we provide
      direct evidence that this core TAP complex is sufficient for (i) ER targeting,
      (ii) heterodimeric assembly within the ER membrane, (iii) peptide binding, (iv)
      peptide transport, and (v) specific inhibition by the herpes simplex virus
      protein ICP47 and the human cytomegalovirus protein US6. We show for the first
      time that the translocation pore of the transporter is composed of the predicted
      TM-(5-10) of TAP1 and TM-(4-9) of TAP2. Moreover, we demonstrate that the N
      terminal domains of TAP1 and TAP2 are essential for recruitment of tapasin,
      consequently mediating assembly of the macromolecular peptide-loading complex.

PMID- 14679199
TI  - Inhibitory regulation of cystic fibrosis transmembrane conductance regulator
      anion-transporting activities by Shank2.
AB  - Accumulating evidence suggests that protein-protein interactions play an
      important role in transepithelial ion transport. In the present study, we report
      on the biochemical and functional association between cystic fibrosis
      transmembrane conductance regulator (CFTR) and a PDZ domain-containing protein
      Shank2. Exploratory reverse transcription-PCR screening revealed mRNAs for
      several members of PDZ domain-containing proteins in epithelial cells. Shank2,
      one of these scaffolding proteins, showed a strong interaction with CFTR by yeast
      two-hybrid assays. Shank2-CFTR interaction was verified by co-immunoprecipitation
      experiments in mammalian cells. Notably, this interaction was abolished by
      mutations in the PDZ domain of Shank2. Protein phosphorylation, HCO(3)(-)
      transport and Cl(-) current by CFTR were measured in NIH 3T3 cells with
      heterologous expression of Shank2. Of interest, expression of Shank2 suppressed
      cAMP-induced phosphorylation and activation of CFTR. Importantly, loss of Shank2
      by stable transfection of antisense-hShank2 plasmid strongly increased CFTR
      currents in colonic T84 cells, in which CFTR and Shank2 were natively expressed.
      Our results indicate that Shank2 negatively regulates CFTR and that this may play
      a significant role in maintaining epithelial homeostasis under normal and
      diseased conditions such as those presented by secretory diarrhea.

PMID- 14679200
TI  - Vasodilator-stimulated phosphoprotein activation of serum-response element
      dependent transcription occurs downstream of RhoA and is inhibited by cGMP
      dependent protein kinase phosphorylation.
AB  - Vasodilator-stimulated phosphoprotein (VASP) associates with cytoskeletal
      structures and promotes F-actin formation. RhoA, a member of the Ras superfamily
      of proteins, activates serum response element (SRE)-dependent transcription
      through changes in actin dynamics. We now show that the F-actin binding region of
      VASP is required for VASP stimulation of SRE-dependent transcription, and that
      VASP is downstream of RhoA in stimulating SRE-dependent transcription. The
      isolated carboxyl-terminal coiled-coil region of VASP mediates protein
      tetramerization and has been used as a dominant negative form of VASP; we found
      that it forms complexes with endogenous VASP in vivo and inhibits in a dose
      dependent fashion serum-, RhoA-, and VASP-stimulated SRE-dependent transcription.
      Cyclic GMP-dependent protein kinase (G-kinase) inhibits RhoA activation of SRE
      dependent transcription (Gudi, T., Chen, J. C., Casteel, D. E., Seasholtz, T. M.,
      Boss, G. R., and Pilz, R. B. (2002) J. Biol. Chem. 277, 37382-37393). We now show
      that the G-kinase inhibition that occurs downstream of RhoA can be explained, at
      least in part, by G-kinase phosphorylation of VASP on Ser(239) at the carboxyl
      terminal end of the G-actin binding site, with some contribution by
      phosphorylation of Ser(157), which is proximal to the profilin binding site. A
      phosphorylation-deficient VASP mutant can partly prevent cGMP/G-kinase inhibition
      of serum- and RhoA-induced SRE-dependent transcription. These studies show that
      VASP, an important component of the cellular microfilament system, plays a major
      role in regulating SRE-dependent transcription, and that G-kinase regulates VASP
      activity.

PMID- 14679202
TI  - Analysis of the role of oligosaccharides in the apoptotic activity of glycodelin
      A.
AB  - Glycodelin A, also known as placental protein-14, is a multifunctional
      glycosylated protein secreted by the uterine endometrium during the early phases
      of pregnancy. It is a known suppressor of T cell proliferation, inducer of T cell
      apoptosis, and inhibitor of sperm zona binding. Unlike in contraceptive activity,
      where the glycans on the molecule have been shown to play a crucial role,
      mutagenesis of the asparagines at sites of N-linked glycosylation (Asn(28) and
      Asn(63)) to glutamine shows that the apoptogenic activity of glycodelin A is
      executed by the protein backbone. Glycosylation at Asn(28) appears to play a role
      in the extracellular secretion of the molecule, as mutation of Asn(28) resulted
      in a significant decrease in the amount of secreted protein, and loss of both
      glycosylation sites reduced the secretion drastically. Our results also suggest
      that the loss of glycosylation does not affect the dimerization status of the
      molecule.

PMID- 14679201
TI  - Inhibition of interleukin-12 p40 transcription and NF-kappaB activation by nitric
      oxide in murine macrophages and dendritic cells.
AB  - Nitric oxide (NO), an important effector molecule of the innate immune system,
      can also regulate adaptive immunity. In this study, the molecular effects of NO
      on the toll-like receptor signaling pathway were determined using interleukin-12
      (IL-12) as an immunologically relevant target gene. The principal conclusion of
      these experiments is that NO inhibits IL-1 receptor-associated kinase (IRAK)
      activity and attenuates the molecular interaction between tumor necrosis factor
      receptor-associated factor-6 and IRAK. As a consequence, the NO donor S-nitroso-N
      acetylpenicillamine (SNAP) inhibits lipopolysaccharide (LPS)-induced IL-12 p40
      mRNA expression, protein production, and promoter activity in murine macrophages,
      dendritic cells, and the murine macrophage cell line RAW 264.7. Splenocytes from
      inducible nitric-oxide synthase-deficient mice demonstrate markedly increased IL
      12 p40 protein and mRNA expression compared with wild type splenocytes. The
      inhibitory action of NO on IL-12 p40 is independent of the cytokine IL-10. The
      effects of NO can be directly attributed to inhibition of NF-kappaB activation
      through IRAK-dependent pathways. Accordingly, SNAP strongly reduces LPS-induced
      NF-kappaB DNA binding to the p40 promoter and inhibits LPS-induced IkappaB
      phosphorylation. Similarly, NO attenuates IL-1beta-induced NF-kappaB activation.
      These experiments provide another example of how an innate immune molecule may
      have a profound effect on adaptive immunity.

PMID- 14679203
TI  - Merlin neutralizes the inhibitory effect of Mdm2 on p53.
AB  - The stability of p53 tumor suppressor is regulated by Mdm2 via the ubiquitination
      and proteasome-mediated proteolysis pathway. The c-Abl and PTEN tumor suppressors
      are known to stabilize p53 by blocking the Mdm2-mediated p53 degradation. This
      study investigated the correlation between p53 and merlin, a neurofibromatosis 2
      (NF2)-related tumor suppressor, in association with the Mdm2 function. The
      results showed that merlin increased the p53 stability by inhibiting the Mdm2
      mediated degradation of p53, which accompanied the increase in the p53-dependent
      transcriptional activity. The stabilization of p53 by merlin appeared to be
      accomplished through Mdm2 degradation, and the N-terminal region of merlin was
      responsible for this novel activity. This study also showed that overexpression
      of merlin-induced apoptosis of cells depending preferentially on p53 in response
      to the serum starvation or a chemotherapeutic agent. These results suggest that
      merlin could be a positive regulator of p53 in terms of tumor suppressor
      activity, and provide the promising therapeutic means for treating tumors with
      non-functional merlin or Mdm2 overexpression.

PMID- 14679204
TI  - Ca2+-dependent protein kinase C isoforms induce cholestasis in rat liver.
AB  - Bile secretion is regulated by different signaling transduction pathways
      including protein kinase C (PKC). However, the role of different PKC isoforms for
      bile formation is still controversial. This study investigates the effects of PKC
      isoform selective activators and inhibitors on PKC translocation, bile secretion,
      bile acid uptake, and subcellular transporter localization in rat liver, isolated
      rat hepatocytes and in HepG2 cells. In rat liver activation of Ca(2+)-dependent
      cPKCalpha and Ca(2+)-independent PKCepsilon by phorbol 12-myristate 13-acetate
      (PMA, 10nmol/liter) is associated with their translocation to the plasma
      membrane. PMA also induced translocation of the cloned rat PKCepsilon fused to a
      yellow fluorescent protein (YFP), which was transfected into HepG2 cells. In the
      perfused liver, PMA induced marked cholestasis. The PKC inhibitors Go6850 (1
      micromol/liter) and Go6976 (0.2 micromol/liter), a selective inhibitor of Ca(2+)
      dependent PKC isoforms, diminished the PMA effect by 50 and 60%, respectively.
      Thymeleatoxin (Ttx,) a selective activator of Ca(2+)-dependent cPKCs, did not
      translocate rat PKCepsilon-YFP transfected in HepG2 cells. However, Ttx (0.5-10
      nmol/liter) induced cholestasis similar to PMA and led to a retrieval of Bsep
      from the canalicular membrane in rat liver while taurocholate-uptake in isolated
      hepatocytes was not affected. Go6976 completely blocked the cholestatic effect of
      Ttx but had no effect on tauroursodeoxycholate-induced choleresis. The data
      identify Ca(2+)-dependent PKC isoforms as inducers of cholestasis. This is mainly
      due to inhibition of taurocholate excretion involving transporter retrieval from
      the canalicular membrane.

PMID- 14679205
TI  - Glycodelin A, not glycodelin S, is apoptotically active. Relevance of sialic acid
      modification.
AB  - Glycodelin, previously known as PP14 (placental protein-14), is a kernel
      lipocalin secreted by the glandular epithelium of the endometrium upon
      progesterone stimulation and by the seminal vesicles. The isoform of the protein
      present in female reproductive tissue, glycodelin A (GdA), and the male
      counterpart, glycodelin S (GdS), have identical amino acid sequences, but
      strikingly different N-linked glycans. It is well documented in literature that
      GdA is an immunosuppressive protein, and we have shown that this activity is due
      to its ability to induce apoptosis in activated T cells. The precise role of GdS
      in seminal plasma is not known. In this study, we report that GdS is not
      apoptotically active. We observe that the apoptotic activity requires the
      presence of sialic acid residues on the complex glycans, as in the case of GdA;
      however, complex glycans of GdS are non-sialylated. We have expressed the wild
      type protein in Pichia pastoris, which does not add sialic acid to the secreted
      proteins, and confirmed our observations that the protein is apoptotically
      inactive in the non-sialylated form. Our results indicate that differential
      glycosylation modulates the function of the different glycodelin isoforms.

PMID- 14679206
TI  - Matrix metalloproteinase 1 interacts with neuronal integrins and stimulates
      dephosphorylation of Akt.
AB  - Several studies have demonstrated that matrix metalloproteinases (MMPs) are
      cytotoxic. The responsible mechanisms, however, are not well understood. MMPs may
      promote cytotoxicity through their ability to disrupt or degrade matrix proteins
      that support cell survival, and MMPs may also cleave substrates to generate
      molecules that stimulate cell death. In addition, MMPs may themselves act on cell
      surface receptors that affect cell survival. Among such receptors is the
      alpha(2)beta(1) integrin, a complex that has previously been linked to leukocyte
      death. In the present study we show that human neurons express alpha(2)beta(1)
      and that pro-MMP-1 interacts with this integrin complex. We also show that
      stimulation of neuronal cultures with MMP-1 is associated with a rapid reduction
      in the phosphorylation of Akt, a kinase that can influence caspase activity and
      cell survival. Moreover, MMP-1-associated dephosphorylation of Akt is inhibited
      by a blocking antibody to the alpha(2) integrin, but not by batimastat, an
      inhibitor of MMP-1 enzymatic activity. Such dephosphorylation is also stimulated
      by a catalytic mutant of pro-MMP-1. Additional studies show that MMP-1 causes
      neuronal death, which is significantly diminished by both a general caspase
      inhibitor and anti-alpha(2) but not by batimastat. Together, these results
      suggest that MMP-1 can stimulate dephosphorylation of Akt and neuronal death
      through a non-proteolytic mechanism that involves changes in integrin signaling.

PMID- 14679207
TI  - Determination of four sequential stages during microautophagy in vitro.
AB  - Microautophagy is the transfer of cytosolic components into the lysosome by
      direct invagination of the lysosomal membrane and subsequent budding of vesicles
      into the lysosomal lumen. This process is topologically equivalent to membrane
      invagination during multivesicular body formation and to the budding of enveloped
      viruses. Vacuoles are lysosomal compartments of yeasts. Vacuolar membrane
      invagination can be reconstituted in vitro with purified yeast vacuoles, serving
      as a model system for budding of vesicles into the lumen of an organelle. Using
      this in vitro system, we defined different reaction states. We identified
      inhibitors of microautophagy in vitro and used them as tools for kinetic
      analysis. This allowed us to characterize four biochemically distinguishable
      steps of the reaction. We propose that these correspond to sequential stages of
      vacuole invagination and vesicle scission. Formation of vacuolar invaginations
      was slow and temperature-dependent, whereas the final scission of the vesicle
      from a preformed invagination was fast and proceeded even on ice. Our
      observations suggest that the formation of invaginations rather than the scission
      of vesicles is the rate-limiting step of the overall reaction.

PMID- 14679208
TI  - RNA binding activity of the ribulose-1,5-bisphosphate carboxylase/oxygenase large
      subunit from Chlamydomonas reinhardtii.
AB  - Transfer of the green algae Chlamydomonas reinhardtii from low light to high
      light generated an oxidative stress that led to a dramatic arrest in the
      synthesis of the large subunit (LSU) of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco). The translational arrest correlated with
      transient changes in the intracellular levels of reactive oxygen species and with
      shifting the glutathione pool toward its oxidized form (Irihimovitch, V., and
      Shapira, M. (2000) J. Biol. Chem. 275, 16289-16295). Here we examined how the
      redox potential of glutathione affected the RNA-protein interactions with the 5'
      untranslated region of rbcL. This RNA region specifically binds a group of
      proteins with molecular masses of 81, 62, 51, and 47 kDa in UV-cross-linking
      experiments under reducing conditions. Binding of these proteins was interrupted
      by exposure to oxidizing conditions (GSSG), and a new protein of 55 kDa was shown
      to interact with the RNA. The 55-kDa protein comigrated with Rubisco LSU in one-
      and two-dimensional gels, and its RNA binding activity was further verified by
      using the purified protein in UV-cross-linking experiments under oxidizing
      conditions. However, the LSU of purified and oxidized Rubisco bound to RNA in a
      sequence-independent manner. A remarkable structural similarity was found between
      the amino-terminal domain of Rubisco LSU in C. reinhardtii and the RNA binding
      domain, a highly prevailing motif among RNA-binding proteins. It appears from the
      crystal structure of Rubisco that the amino terminus of LSU is buried within the
      holoenzyme. We propose that under oxidizing conditions it is exposed to the
      surface and can, therefore, bind RNA. Accordingly, a recombinant form of the
      polypeptide domain that corresponds to the amino terminus of LSU was found to
      bind RNA in vitro with or without GSSG.

PMID- 14679209
TI  - Identification of nucleolin as an AU-rich element binding protein involved in bcl
      2 mRNA stabilization.
AB  - bcl-2 mRNA contains an AU-rich element (ARE) that functions in regulating bcl-2
      stability. Our earlier studies indicated that taxol- or okadaic acid-induced bcl
      2 mRNA destabilization in HL-60 cells is associated with decreased binding of
      trans-acting factors to the ARE. To identify factors that play a role in the
      regulation of bcl-2 mRNA stability, bcl-2 ARE-binding proteins were purified from
      HL-60 cells. Three polypeptides of 100, 70, and 32 kDa were isolated from a bcl-2
      ARE affinity matrix. Matrix-assisted laser desorption ionization mass
      spectroscopy analysis identified these proteins as full-length nucleolin and
      proteolytic fragments of nucleolin. RNA gel shifts assays indicated that
      recombinant nucleolin (residues 284-707) binds specifically to bcl-2 ARE RNA. In
      addition, recombinant nucleolin decreases the rate of decay of mRNA in HL-60 cell
      extracts in an ARE-dependent manner. Taxol or okadaic acid treatment of HL-60
      cells results in proteolysis of nucleolin in a similar time frame as drug-induced
      bcl-2 mRNA down-regulation. These findings suggest that nucleolin functions as a
      bcl-2-stabilizing factor and that taxol and okadaic acid treatment induces
      apoptosis in HL-60 cells through a process that involves down-regulation of
      nucleolin and destabilization of bcl-2 mRNA.

PMID- 14679210
TI  - Apoptotic death in Leishmania donovani promastigotes in response to respiratory
      chain inhibition: complex II inhibition results in increased pentamidine
      cytotoxicity.
AB  - The biochemical changes consequent to respiratory chain inhibition and their
      relationship to cell death in Leishmania spp. remain elusive. Inhibitors of
      respiratory chain complexes I, II, and III were able to induce apoptotic death of
      the bloodstream form of Leishmania donovani. Complex I inhibition resulted in
      mitochondrial hyperpolarization that was preceded by increased superoxide
      production. Limitation of electron transport by thenoyltrifluoroacetone and
      antimycin A, inhibitors of complexes II and III, respectively, resulted in
      dissipation of mitochondrial membrane potential that was sensitive to cyclosporin
      A, a blocker of mitochondrial permeability transition pore. Further studies
      conducted with thenoyltrifluoroacetone showed maximal generation of hydrogen
      peroxide with a moderate elevation of superoxide levels. Complex III inhibition
      provoked superoxide generation only. Interference with complex II but not
      complexes I and III increased intracellular Ca(2+). A tight link between Ca(2+)
      and reactive oxygen species was demonstrated by antioxidant-induced diminution of
      the Ca(2+) increase. However, chelation of extracellular Ca(2+) could not
      abrogate the early increase of reactive oxygen species, providing evidence that
      Ca(2+) elevation was downstream to reactive oxygen species generation. Ca(2+)
      influx occurred through nonselective cation and L-type channels and Na(+)/Ca(2+)
      exchanger-like pathways. Antioxidants such as glutathione and Ca(2+) channel
      blockers reduced apoptotic death. This study provides a new possibility that
      concurrent inhibition of respiratory chain complex II with pentamidine
      administration increases cytotoxicity of the drug. This increased cytotoxicity
      was connected to a 4-fold elevation in intracellular Ca(2+) that was pooled only
      from intracellular sources. Therefore, inhibition of complexes I, II, and III
      leads to apoptosis and complex II inhibition in parallel with pentamidine
      administration-enhanced drug efficacy.

PMID- 14679211
TI  - Regulation of the neuronal nicotinic acetylcholine receptor by SRC family
      tyrosine kinases.
AB  - Src family kinases (SFKs) are abundant in chromaffin cells that reside in the
      adrenal medulla and respond to cholinergic stimulation by secreting
      catecholamines. Our previous work indicated that SFKs regulate acetylcholine- or
      nicotine-induced secretion, but the site of modulatory action was unclear. Using
      whole cell recordings, we found that inhibition of SFK tyrosine kinase activity
      by PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine)
      treatment or expression of a kinase-defective c-Src reduced the peak amplitude of
      nicotine-induced currents in chromaffin cells or in human embryonic kidney cells
      ectopically expressing functional neuronal alpha3beta4alpha5 acetylcholine
      receptors (AChRs). Conversely, the phosphotyrosine phosphatase inhibitor, sodium
      vanadate, or expression of mutationally activated c-Src resulted in enhanced
      current amplitudes. These results suggest that SFKs and putative phosphotyrosine
      phosphatases regulate the activity of AChRs by opposing actions. This proposed
      model was supported further by the findings that SFKs physically associate with
      the receptor and that the AChR is tyrosine-phosphorylated.

PMID- 14679212
TI  - Disabling of receptor activator of nuclear factor-kappaB (RANK) receptor complex
      by novel osteoprotegerin-like peptidomimetics restores bone loss in vivo.
AB  - The tumor necrosis factor family ligand, tumor necrosis factor-related activation
      induced cytokine (TRANCE), and its receptors, receptor activator of nuclear
      factor-kappaB (RANK) and osteoprotegerin (OPG), are known to be regulators of
      development and activation of osteoclasts in bone remodeling. Sustained
      osteoclast activation that occurs through TRANCE-RANK causes osteopenic disorders
      such as osteoporosis and contributes to osteolytic metastases. Here, we report a
      rationally designed small molecule mimic of osteoprotegerin to inhibit osteoclast
      formation in vitro and limit bone loss in an animal model of osteoporosis. One of
      the mimetics, OP3-4, significantly inhibited osteoclast formation in vitro
      (IC(50) = 10 microm) and effectively inhibited total bone loss in ovariectomized
      mice at a dosage of 2 mg/kg/day. Unlike soluble OPG receptors, which preclude
      TRANCE binding to RANK, OP3-4 shows the ability to modulate RANK-TRANCE signaling
      pathways and alters the biological functions of the RANK-TRANCE receptor complex
      by facilitating a defective receptor complex. These features suggest that OPG
      derived small molecules can be used as a probe to understand complex biological
      functions of RANK-TRANCE-OPG receptors and also can be used as a platform to
      develop more useful therapeutic agents for inflammation and bone disease.

PMID- 14679213
TI  - Identification of an autoregulatory feedback pathway involving interleukin-1alpha
      in induction of constitutive NF-kappaB activation in pancreatic cancer cells.
AB  - We previously reported that NF-kappaB is constitutively activated in most human
      pancreatic cancer tissues and cell lines but not in normal pancreatic tissues and
      immortalized pancreatic ductal epithelial cells. IkappaBalphaM-mediated
      inhibition of constitutive NF-kappaB activity in human pancreatic cancer cells
      suppressed tumorigenesis and liver metastasis in an orthotopic nude mouse model,
      suggesting that constitutive NF-kappaB activation plays an important role in
      pancreatic tumor progression and metastasis. However, the underlying mechanism by
      which NF-kappaB is activated in pancreatic cancer remains to be elucidated. In
      this study, we found that an autocrine mechanism accounts for the constitutive
      activation of NF-kappaB in metastatic human pancreatic cancer cell lines. Further
      investigation showed that interleukin-1alpha was the primary cytokine secreted by
      these cells that activates NF-kappaB. Neutralization of interleukin-1alpha
      activity suppressed the constitutive activation of NF-kappaB and the expression
      of its downstream target gene, urokinase-type plasminogen activator, in
      metastatic pancreatic cancer cell lines. Our results demonstrate that regulation
      of interleukin-1alpha expression is primarily dependent on AP-1 activity, which
      is in part induced by signaling pathways that are epidermal growth factor
      receptor-dependent and -independent. In conclusion, our findings suggest a
      possible mechanism for the constitutive activation of NF-kappaB in metastatic
      human pancreatic cancer cells and a possible missing mechanistic link between
      inflammation and cancer.

PMID- 14679214
TI  - A novel proteomic screen for peptide-protein interactions.
AB  - Regulated interactions between short, unstructured amino acid sequences and
      modular protein domains are central to cell signaling. Here we use synthetic
      peptides in "active" (e.g. phosphorylated) and "control" (e.g. non
      phosphorylated) forms as baits in affinity pull-down experiments to determine
      such interactions by quantitative proteomics. Stable isotope labeling by amino
      acids in cell culture distinguishes specific binders directly by the isotope
      ratios determined by mass spectrometry (Blagoev, B., Kratchmarova, I., Ong, S.
      E., Nielsen, M., Foster, L. J., and Mann, M. (2003) Nat. Biotechnol. 21, 315
      318). A tyrosine-phosphorylated peptide of the epidermal growth factor receptor
      specifically retrieved the Src homology domain (SH) 2- and SH3 domain-containing
      adapter protein Grb2. A proline-rich sequence of Son of Sevenless also
      specifically bound Grb2, demonstrating that the screen maintains specificity with
      low affinity interactions. The proline-rich Sos peptide retrieved only SH3 domain
      containing proteins as specific binding partners. Two of these, Pacsin 3 and
      Sorting Nexin 9, were confirmed by immunoprecipitation. Our data are consistent
      with a change in the role of Sos from Ras-dependent signaling to actin
      remodeling/endocytic signaling events by a proline-SH3 domain switch.

PMID- 14679215
TI  - 14-3-3beta binds to big mitogen-activated protein kinase 1 (BMK1/ERK5) and
      regulates BMK1 function.
AB  - Big mitogen-activated kinase 1 (BMK1/ERK5) is a member of the MAPK family
      activated by growth factors that mediates cell growth and survival. Previous data
      show that BMK1 can be activated by steady laminar flow and is atheroprotective by
      preventing endothelial cells from undergoing apoptosis. The primary structure of
      BMK1 is distinct from other MAPK members by virtue of a unique long C-tail,
      suggesting specific mechanisms of regulation. To characterize regulatory
      mechanisms for BMK1 function, we identified binding proteins by yeast two-hybrid
      analysis. Among these proteins, the scaffolding protein 14-3-3 was identified.
      BMK1 bound to 14-3-3beta in vitro and in vivo as demonstrated by glutathione S
      transferase (GST)-14-3-3beta fusion protein pull-down assays and
      coimmunoprecipitation. Phosphorylation of BMK1 was most likely required for this
      interaction. GST-14-3-3beta pull-down assays using truncated constructs of BMK1
      and site-directed BMK1 mutants demonstrated that the interaction requires serine
      486 within the C terminus of BMK1. BMK1 bound to 14-3-3beta basally, and the
      interaction was greatly abrogated when BMK1 was activated. The interaction of 14
      3-3beta and BMK1 inhibited kinase activities stimulated by constitutively active
      (CA)-MEK5 and epidermal growth factor. Mutation of serine 486 (BMK1-S486A)
      prevented the interaction with 14-3-3beta and enhanced BMK1 activity upon
      epidermal growth factor stimulation. These data demonstrate an inhibitory
      function for 14-3-3beta binding to BMK1 and show that serine 486 phosphorylation
      represents a novel regulatory mechanism for BMK1.

PMID- 14679216
TI  - Mutual regulation of protein-tyrosine phosphatase 20 and protein-tyrosine kinase
      Tec activities by tyrosine phosphorylation and dephosphorylation.
AB  - PTP20, also known as HSCF/protein-tyrosine phosphatase K1/fetal liver phosphatase
      1/brain-derived phosphatase 1, is a cytosolic protein-tyrosine phosphatase with
      currently unknown biological relevance. We have identified that the nonreceptor
      protein-tyrosine kinase Tec-phosphorylated PTP20 on tyrosines and co
      immunoprecipitated with the phosphatase in a phosphotyrosine-dependent manner.
      The interaction between the two proteins involved the Tec SH2 domain and the C
      terminal tyrosine residues Tyr-281, Tyr-303, Tyr-354, and Tyr-381 of PTP20, which
      were also necessary for tyrosine phosphorylation/dephosphorylation. Association
      between endogenous PTP20 and Tec was also tyrosine phosphorylation-dependent in
      the immature B cell line Ramos. Finally, the Tyr-281 residue of PTP20 was shown
      to be critical for deactivating Tec in Ramos cells upon B cell receptor ligation
      as well as dephosphorylation and deactivation of Tec and PTP20 itself in
      transfected COS7 cells. Taken together, PTP20 appears to play a negative role in
      Tec-mediated signaling, and Tec-PTP20 interaction might represent a negative
      feedback mechanism.

PMID- 14679217
TI  - The preferred substrate for RecA-mediated cleavage of bacteriophage 434 repressor
      is the DNA-bound dimer.
AB  - Induction of a lysogen of a lambdoid bacteriophage usually involves RecA
      stimulated autoproteolysis of the bacteriophage repressor protein. Previous work
      on the phage repressors showed that the monomeric form of the protein is the
      target of RecA. Our previous work indicated that in the case of bacteriophage
      434, virtually none of the repressor is present as a monomer in vivo. Hence, if
      the repressor in a lysogen is present as a dimer, how can RecA-stimulated
      autoproteolysis play a role in bacteriophage induction? We examined this question
      by determining the rate of RecA-stimulated 434 repressor cleavage as a function
      of repressor concentration and added DNA. Our results show that binding of 434
      repressor to a specific DNA binding site dramatically increases the velocity of
      repressor autocleavage compared to the velocity of cleavage of the monomer and
      concentration-induced dimer. DNA binding-deficient hemidimers formed between the
      intact repressor and its C-terminal domain fragment have a lower rate of cleavage
      than DNA-bound dimers. These results show that the DNA-bound 434 repressor dimer,
      which is the form of the repressor that is required for its transcriptional
      regulatory functions, is the preferred form for RecA-stimulated autocleavage. We
      also show that the rate of repressor autocleavage is influenced by the sequence
      of the bound DNA. Kinetic analysis of the autocleavage reaction indicated that
      the DNA sequence influences the velocity of 434 repressor autocleavage by
      affecting the affinity of the repressor-DNA complex for RecA, not the chemical
      cleavage step. Regardless of the mechanism, the finding that the presence and
      precise sequence of DNA modulate the autocleavage reaction shows that DNA
      allosterically affects the function of 434 repressor.

PMID- 14679218
TI  - Cysteinyl-tRNA(Cys) formation in Methanocaldococcus jannaschii: the mechanism is
      still unknown.
AB  - Most organisms form Cys-tRNA(Cys), an essential component for protein synthesis,
      through the action of cysteinyl-tRNA synthetase (CysRS). However, the genomes of
      Methanocaldococcus jannaschii, Methanothermobacter thermautotrophicus, and
      Methanopyrus kandleri do not contain a recognizable cysS gene encoding CysRS. It
      was reported that M. jannaschii prolyl-tRNA synthetase (C. Stathopoulos, T. Li,
      R. Longman, U. C. Vothknecht, H. D. Becker, M. Ibba, and D. Soll, Science 287:479
      482, 2000; R. S. Lipman, K. R. Sowers, and Y. M. Hou, Biochemistry 39:7792-7798,
      2000) or the M. jannaschii MJ1477 protein (C. Fabrega, M. A. Farrow, B.
      Mukhopadhyay, V. de Crecy-Lagard, A. R. Ortiz, and P. Schimmel, Nature 411:110
      114, 2001) provides the "missing" CysRS activity for in vivo Cys-tRNA(Cys)
      formation. These conclusions were supported by complementation of temperature
      sensitive Escherichia coli cysS(Ts) strain UQ818 with archaeal proS genes
      (encoding prolyl-tRNA synthetase) or with the Deinococcus radiodurans DR0705
      gene, the ortholog of the MJ1477 gene. Here we show that E. coli UQ818 harbors a
      mutation (V27E) in CysRS; the largest differences compared to the wild-type
      enzyme are a fourfold increase in the K(m) for cysteine and a ninefold reduction
      in the k(cat) for ATP. While transformants of E. coli UQ818 with archaeal and
      bacterial cysS genes grew at a nonpermissive temperature, growth was also
      supported by elevated intracellular cysteine levels, e.g., by transformation with
      an E. coli cysE allele (encoding serine acetyltransferase) or by the addition of
      cysteine to the culture medium. An E. coli cysS deletion strain permitted a
      stringent complementation test; growth could be supported only by archaeal or
      bacterial cysS genes and not by archaeal proS genes or the D. radiodurans DR0705
      gene. Construction of a D. radiodurans DR0705 deletion strain showed this gene to
      be dispensable. However, attempts to delete D. radiodurans cysS failed,
      suggesting that this is an essential Deinococcus gene. These results imply that
      it is not established that proS or MJ1477 gene products catalyze Cys-tRNA(Cys)
      synthesis in M. jannaschii. Thus, the mechanism of Cys-tRNA(Cys) formation in M.
      jannaschii still remains to be discovered.

PMID- 14679219
TI  - Diversifying selection at the Bacillus quorum-sensing locus and determinants of
      modification specificity during synthesis of the ComX pheromone.
AB  - The competence quorum-sensing system of Bacillus subtilis consists of two
      component regulatory proteins, ComP (histidine kinase) and the response
      regulator, ComA, an extracellular pheromone (ComX), and a protein that is needed
      for the proteolytic cleavage and modification of pre-ComX (ComQ). ComQ and pre
      ComX are both necessary and sufficient for the production of active pheromone,
      which is released as an isoprenylated peptide. Laboratory strain 168 and a number
      of natural isolates of bacilli differ in the primary sequences of their
      pheromones as well as in the masses of their isoprenyl adducts. We have shown
      that ComX, ComQ, and the membrane-localized sensor domain of ComP are highly
      polymorphic in natural isolates of bacilli all closely related to the laboratory
      strain of B. subtilis. In this study, we used two statistical tests (the ratio of
      synonymous and nonsynonymous substitution rates and the Tajima D test) to
      demonstrate that these polymorphic sequences evolved by diversifying selection
      rather than by neutral drift. We show that the choice of isoprenyl derivative is
      determined by the C-terminal (mature) sequence of pre-ComX rather than by the
      ComQ protein. The implications of these findings for the evolution of the quorum
      sensing system and for the protein-protein interactions involved in determining
      specificity are discussed.

PMID- 14679220
TI  - Multiple formate dehydrogenase enzymes in the facultative methylotroph
      Methylobacterium extorquens AM1 are dispensable for growth on methanol.
AB  - Formate dehydrogenase has traditionally been assumed to play an essential role in
      energy generation during growth on C(1) compounds. However, this assumption has
      not yet been experimentally tested in methylotrophic bacteria. In this study, a
      whole-genome analysis approach was used to identify three different formate
      dehydrogenase systems in the facultative methylotroph Methylobacterium extorquens
      AM1 whose expression is affected by either molybdenum or tungsten. A complete set
      of single, double, and triple mutants was generated, and their phenotypes were
      analyzed. The growth phenotypes of the mutants suggest that any one of the three
      formate dehydrogenases is sufficient to sustain growth of M. extorquens AM1 on
      formate, while surprisingly, none is required for growth on methanol or
      methylamine. Nuclear magnetic resonance analysis of the fate of [(13)C]methanol
      revealed that while cells of wild-type M. extorquens AM1 as well as cells of all
      the single and the double mutants continuously produced [(13)C]bicarbonate and
      (13)CO(2), cells of the triple mutant accumulated [(13)C]formate instead. Further
      studies of the triple mutant showed that formate was not produced quantitatively
      and was consumed later in growth. These results demonstrated that all three
      formate dehydrogenase systems must be inactivated in order to disrupt the formate
      oxidizing capacity of the organism but that an alternative formate-consuming
      capacity exists in the triple mutant.

PMID- 14679221
TI  - Influence of growth temperature on lipid and phosphate contents of surface
      polysaccharides from the antarctic bacterium Pseudoalteromonas haloplanktis TAC
      125.
AB  - The chemical structural variations induced by different growth temperatures in
      the lipooligosaccharide and exopolysaccharide components extracted from the
      Antarctic bacterium Pseudoalteromonas haloplanktis TAC 125 are described. The
      increase in phosphorylation with the increase in growth temperature seems to be
      general, because it happens not only for the lipooligosaccharide but also for the
      exopolysaccharide. Structural variations in the lipid components of lipid A also
      occur. In addition, free lipid A is found at both 25 and 4 degrees C but not at
      15 degrees C, which is the optimal growth temperature, suggesting a incomplete
      biosynthesis of the lipooligosaccharide component under the first two temperature
      conditions.

PMID- 14679222
TI  - Characterization of CmaA, an adenylation-thiolation didomain enzyme involved in
      the biosynthesis of coronatine.
AB  - Several pathovars of Pseudomonas syringae produce the phytotoxin coronatine
      (COR), which contains an unusual amino acid, the 1-amino-2-ethylcyclopropane
      carboxylic acid called coronamic acid (CMA), which is covalently linked to a
      polyketide-derived carboxylic acid, coronafacic acid, by an amide bond. The
      region of the COR biosynthetic gene cluster proposed to be responsible for CMA
      biosynthesis was resequenced, and errors in previously deposited cmaA sequences
      were corrected. These efforts allowed overproduction of P. syringae pv. glycinea
      PG4180 CmaA in P. syringae pv. syringae FF5 as a FLAG-tagged protein and
      overproduction of P. syringae pv. tomato CmaA in Escherichia coli as a His-tagged
      protein; both proteins were in an enzymatically active form. Sequence analysis of
      CmaA indicated that there were two domains, an adenylation domain (A domain) and
      a thiolation domain (T domain). ATP-(32)PP(i) exchange assays showed that the A
      domain of CmaA catalyzes the conversion of branched-chain L-amino acids and ATP
      into the corresponding aminoacyl-AMP derivatives, with a kinetic preference for L
      allo-isoleucine. Additional experiments demonstrated that the T domain of CmaA,
      which is posttranslationally modified with a 4'-phosphopantetheinyl group, reacts
      with the AMP derivative of L-allo-isoleucine to produce an aminoacyl thiolester
      intermediate. This covalent species was detected by incubating CmaA with ATP and
      L-[G-(3)H]allo-isoleucine, followed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analysis. It is postulated that the L-allo-isoleucine covalently
      tethered to CmaA serves as the substrate for additional enzymes in the CMA
      biosynthetic pathway that catalyze cyclopropane ring formation, which is followed
      by thiolester hydrolysis, yielding free CMA. The availability of catalytically
      active CmaA should facilitate elucidation of the details of the subsequent steps
      in the formation of this novel cyclopropyl amino acid.

PMID- 14679223
TI  - Temporal expression of pertussis toxin and Ptl secretion proteins by Bordetella
      pertussis.
AB  - Pertussis toxin is an AB(5) toxin comprised of protein subunits S1 through S5.
      The individual subunits are secreted by a Sec-dependent mechanism into the
      periplasm, where the toxin is assembled. The Ptl type IV secretion system
      mediates secretion of assembled toxin past the outer membrane. In this study, we
      examined the time course of protein expression, toxin assembly, and secretion as
      a function of the bacterial growth cycle. Logarithmic growth was observed after a
      1-h lag phase. Secreted toxin was first observed at 3 h. Secretion continued
      throughout the logarithmic growth phase and decreased as the culture entered the
      stationary phase after about 24 h. On a per cell basis, toxin secretion occurred
      at a constant rate of 3 molecules/min/cell from 2 to 18 h. More of toxin subunits
      S1, S2, and S3 were produced than were secreted, resulting in periplasmic
      accumulation. Periplasmic S1, S2, and S3 were found to be soluble in the
      periplasm, as well as membrane associated. About one-half of the periplasmic S1,
      S2 and S3 subunits were incorporated into holotoxin. Secretion component PtlF was
      present at a low level at time zero, and the level increased between 2 and 24 h
      from 30 to 1,000 molecules per cell; however, the initial level of PtlF, 30
      molecules per cell, supported maximal secretion. The accumulation of both
      periplasmic toxin and secretion components suggests that translation rates exceed
      the rate of secretion and that secretion, not toxin and Ptl complex assembly, is
      rate limiting.

PMID- 14679224
TI  - Analysis of differences in the functional properties of the substrate binding
      proteins of the Borrelia burgdorferi oligopeptide permease (Opp) operon.
AB  - The Borrelia burgdorferi genome encodes five orthologues of the substrate binding
      protein oligopeptide permease A (OppA). It was previously shown that these genes
      are under the control of separate promoters and are differentially expressed
      under various environmental conditions. We were interested in determining whether
      there are also differences in substrate specificities among the proteins. The
      substrate specificities of recombinant proteins were determined by screening for
      high-affinity peptides by use of a combinatorial phage display heptapeptide
      library. Different heptapeptides with high affinities for OppA-1, OppA-2, and
      OppA-3 were identified. No heptapeptide binding OppA-4 or OppA-5 could be
      identified. Competitive binding assays were performed under various conditions to
      determine the substrate preferences of the OppA proteins. OppA-1 retained maximal
      activity over a broad range of pHs (5.5 to 7.5), whereas OppA-2 and OppA-3 showed
      peak activities at pHs below 5.5. OppA-1 and OppA-2 showed preferences for
      tripeptides over dipeptides and longer-chain peptides. Although a wide variety of
      amino acyl side chains were tolerated by all three OppA proteins, OppA-1 showed
      the broadest substrate specificity and was able to accommodate peptides composed
      of bulky hydrophobic residues; OppA-2 and OppA-3 showed preferences for peptides
      composed of small nonpolar amino acids. All three OppA proteins showed
      preferences for peptides composed of L- rather than D-amino acids. OppA-3 showed
      the greatest tolerance for changes in stereochemistry. Substantial differences in
      the substrate specificities of the OppA proteins of B. burgdorferi suggest that
      they may have distinct functions in the organism.

PMID- 14679225
TI  - Staphylococcus aureus mevalonate kinase: isolation and characterization of an
      enzyme of the isoprenoid biosynthetic pathway.
AB  - It has been proposed that isoprenoid biosynthesis in several gram-positive cocci
      depends on the mevalonate pathway for conversion of acetyl coenzyme A to
      isopentenyl diphosphate. Mevalonate kinase catalyzes a key reaction in this
      pathway. In this study the enzyme from Staphylococcus aureus was expressed in
      Escherichia coli, isolated in a highly purified form, and characterized. The
      overall amino acid sequence of this enzyme was very heterologous compared with
      the sequences of eukaryotic mevalonate kinases. Analysis by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and analytical gel filtration
      chromatography suggested that the native enzyme is a monomer with a molecular
      mass of approximately 33 kDa. The specific activity was 12 U/mg, and the pH
      optimum was 7.0 to 8.5. The apparent K(m) values for R,S-mevalonate and ATP were
      41 and 339 micro M, respectively. There was substantial substrate inhibition at
      millimolar levels of mevalonate. The sensitivity to feedback inhibition by
      farnesyl diphosphate and its sulfur-containing analog, farnesyl thiodiphosphate,
      was characterized. These compounds were competitive inhibitors with respect to
      ATP; the K(i) values were 46 and 45 micro M for farnesyl diphosphate and its thio
      analog, respectively. Parallel measurements with heterologous eukaryotic
      mevalonate kinases indicated that S. aureus mevalonate kinase is much less
      sensitive to feedback inhibition (K(i) difference, 3 orders of magnitude) than
      the human enzyme. In contrast, both enzymes tightly bound trinitrophenyl-ATP, a
      fluorescent substrate analog, suggesting that there are similarities in
      structural features that are important for catalytic function.

PMID- 14679227
TI  - Production of muramic delta-lactam in Bacillus subtilis spore peptidoglycan.
AB  - Bacterial spore heat resistance is primarily dependent upon dehydration of the
      spore cytoplasm, a state that is maintained by the spore peptidoglycan wall, the
      spore cortex. A peptidoglycan structural modification found uniquely in spores is
      the formation of muramic delta-lactam. Production of muramic delta-lactam in
      Bacillus subtilis requires removal of a peptide side chain from the N
      acetylmuramic acid residue by a cwlD-encoded muramoyl-L-Alanine amidase.
      Expression of cwlD takes place in both the mother cell and forespore compartments
      of sporulating cells, though expression is expected to be required only in the
      mother cell, from which cortex synthesis derives. Expression of cwlD in the
      forespore is in a bicistronic message with the upstream gene ybaK. We show that
      ybaK plays no apparent role in spore peptidoglycan synthesis and that expression
      of cwlD in the forespore plays no significant role in spore peptidoglycan
      formation. Peptide cleavage by CwlD is apparently followed by deacetylation of
      muramic acid and lactam ring formation. The product of pdaA (yfjS), which encodes
      a putative deacetylase, has recently been shown to also be required for muramic
      delta-lactam formation. Expression of CwlD in Escherichia coli results in
      muramoyl L-Alanine amidase activity but no muramic delta-lactam formation.
      Expression of PdaA alone in E. coli had no effect on E. coli peptidoglycan
      structure, whereas expression of CwlD and PdaA together resulted in the formation
      of muramic delta-lactam. CwlD and PdaA are necessary and sufficient for muramic
      delta-lactam production, and no other B. subtilis gene product is required. PdaA
      probably carries out both deacetylation and lactam ring formation and requires
      the product of CwlD activity as a substrate.

PMID- 14679226
TI  - RtsA coordinately regulates DsbA and the Salmonella pathogenicity island 1 type
      III secretion system.
AB  - Salmonella serovars cause a wide variety of diseases ranging from mild
      gastroenteritis to life-threatening systemic infections. An important step in
      Salmonella enterica serovar Typhimurium infection is the invasion of
      nonphagocytic epithelial cells, mediated by a type III secretion system (TTSS)
      encoded on Salmonella pathogenicity island 1 (SPI1). The SPI1 TTSS forms a needle
      complex through which effector proteins are injected into the cytosol of host
      cells, where they promote actin rearrangement and engulfment of the bacteria. We
      previously identified the Salmonella-specific regulatory protein RtsA, which
      induces expression of hilA and, thus, the SPI1 genes. Here we show that the hilA
      regulators RtsA, HilD, and HilC can each induce transcription of dsbA, which
      encodes a periplasmic disulfide bond isomerase. RtsA induces expression of dsbA
      independent of either the SPI1 TTSS or the only known regulator of dsbA, the
      CpxRA two-component system. We show that DsbA is required for both the SPI1 and
      SPI2 TTSS to translocate effector proteins into the cytosol of host cells. DsbA
      is also required for survival during the systemic stages of infection. We also
      present evidence that production of SPI1 effector proteins is coupled to assembly
      of the TTSS. This feedback regulation is mediated at either the transcriptional
      or posttranscriptional level, depending on the particular effector. Loss of DsbA
      leads to feedback inhibition, which is consistent with the hypothesis that
      disulfide bond formation plays a role in TTSS assembly or function.

PMID- 14679228
TI  - Flavin mononucleotide-binding flavoprotein family in the domain Archaea.
AB  - The protein (AfpA, for archaeoflavoprotein) encoded by AF1518 in the genome of
      Archaeoglobus fulgidus was produced in Escherichia coli and characterized. AfpA
      was found to be a homodimer with a native molecular mass of 43 kDa and containing
      two noncovalently bound flavin mononucleotides (FMNs). The cell extract of A.
      fulgidus catalyzed the CO-dependent reduction of AfpA that was stimulated by the
      addition of ferredoxin. Ferredoxin was found to be a direct electron donor to
      purified AfpA, whereas rubredoxin was unable to substitute. Neither NADH nor
      NADPH was an electron donor. Ferricyanide, 2,6-dichlorophenolindophenol, several
      quinones, ferric citrate, bovine cytochrome c, and O(2) accepted electrons from
      reduced AfpA, whereas coenzyme F(420) did not. The rate of cytochrome c reduction
      was enhanced in the presence of O(2) suggesting that superoxide is a product of
      the interaction of reduced AfpA with O(2). Although AF1518 was previously
      annotated as encoding a decarboxylase involved in coenzyme A biosynthesis, the
      results establish that AfpA is an electron carrier protein with ferredoxin as the
      physiological electron donor. The genomes of several diverse Archaea contained
      afpA homologs clustered with open reading frames annotated as homologs of genes
      encoding reductases involved in the oxidative stress response of anaerobes from
      the domain Bacteria. A potential role for AfpA in coupling electron flow from
      ferredoxin to the putative reductases is discussed. A search of the databases
      suggests that AfpA is the prototype of a previously unrecognized flavoprotein
      family unique to the domain Archaea for which the name archaeoflavoprotein is
      proposed.

PMID- 14679229
TI  - NpdR, a repressor involved in 2,4,6-trinitrophenol degradation in Rhodococcus
      opacus HL PM-1.
AB  - Rhodococcus opacus HL PM-1 utilizes 2,4,6-trinitrophenol (picric acid) as a sole
      nitrogen source. The initial attack on picric acid occurs through two
      hydrogenation reactions. Hydride transferase II (encoded by npdI) and hydride
      transferase I (encoded by npdC) are responsible for the hydride transfers.
      Database searches with the npd genes have indicated the presence of a putative
      transcriptional regulator, npdR. Here, the npdR gene was expressed in Escherichia
      coli, and the protein was purified and shown to form a complex with intergenic
      regions between open reading frames A and B and between npdH and npdI within the
      npd gene cluster. A change in DNA-NpdR complex formation occurred in the presence
      of 2,4-dinitrophenol, picric acid, 2-chloro-4,6-dinitrophenol, and 2-methyl-4,6
      dinitrophenol. By constructing a promoter-probe vector, we demonstrated that both
      intergenic regions caused the expression of reporter gene xylE. Hence, both of
      these regions contain promoters. A deletion mutant of R. opacus HL PM-1 was
      constructed in which part of npdR was deleted. The expression of npdI and npdC
      was induced by 2,4-dinitrophenol in the wild-type strain, while in the mutant
      these genes were constitutively expressed. Hence, NpdR is a repressor involved in
      picric acid degradation.

PMID- 14679230
TI  - Genomic interrogation of the dassie bacillus reveals it as a unique RD1 mutant
      within the Mycobacterium tuberculosis complex.
AB  - Despite their remarkable genetic homology, members of the Mycobacterium
      tuberculosis complex express very different phenotypes, most notably in their
      spectra of clinical presentation. For example, M. tuberculosis is regarded as
      pathogenic to humans, whereas members having deleted RD1, such as Mycobacterium
      microti and Mycobacterium bovis BCG, are not. The dassie bacillus, an infrequent
      variant of the M. tuberculosis complex characterized as being most similar to M.
      microti, is the causative agent of tuberculosis (TB) in the dassie (Procavia
      capensis). Intriguingly, the dassie bacillus is not pathogenic to rabbits or
      guinea pigs and has never been documented to infect humans. Although it was
      identified more than a half-century ago, the reasons behind its attenuation are
      unknown. Because large sequence polymorphisms have presented themselves as the
      most obvious genomic distinction among members of the M. tuberculosis complex,
      the DNA content of the dassie bacillus was interrogated by Affymetrix GeneChip to
      identify regions that are absent from it but present in M. tuberculosis H37Rv.
      Comparison has led to the identification of nine regions of difference (RD), five
      of which are shared with M. microti (RDs 3, 7, 8, 9, and 10). Although the dassie
      bacillus does not share the other documented deletions in M. microti (RD1(mic),
      RD5(mic), MID1, MID2, and MID3), it has endured unique deletions in the regions
      of RD1, RD5, N-RD25, and Rv3081-Rv3082c (virS). RD1(das), affecting only Rv3874
      Rv3877, is the smallest natural deletion of the RD1 region uncovered and points
      to genes within this region that are likely implicated in virulence. Newfound
      deletions from the dassie bacillus are discussed in relation to their
      evolutionary and biological significance.

PMID- 14679231
TI  - Natural selection and evolution of streptococcal virulence genes involved in
      tissue-specific adaptations.
AB  - The molecular mechanisms underlying niche adaptation in bacteria are not fully
      understood. Primary infection by the pathogen group A streptococcus (GAS) takes
      place at either the throat or the skin of its human host, and GAS strains differ
      in tissue site preference. Many skin-tropic strains bind host plasminogen via the
      plasminogen-binding group A streptococcal M protein (PAM) present on the cell
      surface; inactivation of genes encoding either PAM or streptokinase (a
      plasminogen activator) leads to loss of virulence at the skin. Unlike PAM, which
      is present in only a subset of GAS strains, the gene encoding streptokinase (ska)
      is present in all GAS isolates. In this study, the evolution of the virulence
      genes known to be involved in skin infection was examined. Most genetic diversity
      within ska genes was localized to a region encoding the plasminogen-docking
      domain (beta-domain). The gene encoding PAM displayed strong linkage
      disequilibrium (P << 0.01) with a distinct phylogenetic cluster of the ska beta
      domain-encoding region. Yet, ska alleles of distant taxa showed a history of
      intragenic recombination, and high intrinsic levels of recombination were found
      among GAS strains having different tissue tropisms. The data suggest that tissue
      specific adaptations arise from epistatic coselection of bacterial virulence
      genes. Additional analysis of ska genes showed that approximately 4% of the
      codons underwent strong diversifying selection. Horizontal acquisition of one ska
      lineage from a commensal Streptococcus donor species was also evident. Together,
      the data suggest that new phenotypes can be acquired through interspecies
      recombination between orthologous genes, while constrained functions can be
      preserved; in this way, orthologous genes may provide a rich and ready source for
      new phenotypes and thereby play a facilitating role in the emergence of new niche
      adaptations in bacteria.

PMID- 14679232
TI  - Growth phase-dependent regulation and stringent control of fis are conserved
      processes in enteric bacteria and involve a single promoter (fis P) in
      Escherichia coli.
AB  - The intracellular concentration of the Escherichia coli factor for inversion
      stimulation (Fis), a global regulator of transcription and a facilitator of
      certain site-specific DNA recombination events, varies substantially in response
      to changes in the nutritional environment and growth phase. Under conditions of
      nutritional upshift, fis is transiently expressed at very high levels, whereas
      under induced starvation conditions, fis is repressed by stringent control. We
      show that both of these regulatory processes operate on the chromosomal fis genes
      of the enterobacteria Klebsiella pneumoniae, Serratia marcescens, Erwinia
      carotovora, and Proteus vulgaris, strongly suggesting that the physiological role
      of Fis is closely tied to its transcriptional regulation in response to the
      nutritional environment. These transcriptional regulatory processes were
      previously shown to involve a single promoter (fis P) preceding the fis operon in
      E. coli. Recent work challenged this notion by presenting evidence from primer
      extension assays which appeared to indicate that there are multiple promoters
      upstream of fis P that contribute significantly to the expression and regulation
      of fis in E. coli. Thus, a rigorous analysis of the fis promoter region was
      conducted to assess the contribution of such additional promoters. However, our
      data from primer extension analysis, S1 nuclease mapping, beta-galactosidase
      assays, and in vitro transcription analysis all indicate that fis P is the sole
      E. coli fis promoter in vivo and in vitro. We further show how certain conditions
      used in the primer extension reactions can generate artifacts resulting from
      secondary annealing events that are the likely source of incorrect assignment of
      additional fis promoters.

PMID- 14679233
TI  - Ruminococcus albus 8 mutants defective in cellulose degradation are deficient in
      two processive endocellulases, Cel48A and Cel9B, both of which possess a novel
      modular architecture.
AB  - The cellulolytic bacterium Ruminococcus albus 8 adheres tightly to cellulose, but
      the molecular biology underpinning this process is not well characterized.
      Subtractive enrichment procedures were used to isolate mutants of R. albus 8 that
      are defective in adhesion to cellulose. Adhesion of the mutant strains was
      reduced 50% compared to that observed with the wild-type strain, and cellulose
      solubilization was also shown to be slower in these mutant strains, suggesting
      that bacterial adhesion and cellulose solubilization are inextricably linked. Two
      dimensional polyacrylamide gel electrophoresis showed that all three mutants
      studied were impaired in the production of two high-molecular-mass, cell-bound
      polypeptides when they were cultured with either cellobiose or cellulose. The
      identities of these proteins were determined by a combination of mass
      spectrometry methods and genome sequence data for R. albus 8. One of the
      polypeptides is a family 9 glycoside hydrolase (Cel9B), and the other is a family
      48 glycoside hydrolase (Cel48A). Both Cel9B and Cel48A possess a modular
      architecture, Cel9B possesses features characteristic of the B(2) (or theme D)
      group of family 9 glycoside hydrolases, and Cel48A is structurally similar to the
      processive endocellulases CelF and CelS from Clostridium cellulolyticum and
      Clostridium thermocellum, respectively. Both Cel9B and Cel48A could be recovered
      by cellulose affinity procedures, but neither Cel9B nor Cel48A contains a
      dockerin, suggesting that these polypeptides are retained on the bacterial cell
      surface, and recovery by cellulose affinity procedures did not involve a
      clostridium-like cellulosome complex. Instead, both proteins possess a single
      copy of a novel X module with an unknown function at the C terminus. Such X
      modules are also present in several other R. albus glycoside hydrolases and are
      phylogentically distinct from the fibronectin III-like and X modules identified
      so far in other cellulolytic bacteria.

PMID- 14679234
TI  - In Pseudomonas syringae pv. phaseolicola, expression of the argK gene, encoding
      the phaseolotoxin-resistant ornithine carbamoyltransferase, is regulated
      indirectly by temperature and directly by a precursor resembling
      carbamoylphosphate.
AB  - Pseudomonas syringae pv. phaseolicola synthesizes a non-host-specific toxin,
      phaseolotoxin, and also synthesizes a phaseolotoxin-resistant ornithine
      carbamoyltransferase (ROCT) to protect itself from its own toxin. ROCT is encoded
      by argK, which is expressed coordinately with phaseolotoxin synthesis at 18
      degrees C. To investigate the regulatory mechanisms of this system, null mutants
      were constructed for argK, argF (encoding the phaseolotoxin-sensitive OCTase
      [SOCT]), and amtA (encoding an amidinotransferase involved in phaseolotoxin
      synthesis). The argF mutant did not exhibit arginine auxotrophy when grown in M9
      medium at 28 degrees C, because under this condition SOCT was replaced by ROCT.
      This loss of thermoregulation of argK was apparently caused by accumulation of
      carbamoylphosphate, one of the substrates of SOCT. Carbamoylphosphate, which has
      a structure similar to that of the inorganic moiety of phaseolotoxin, was used in
      induction assays with wild-type P. syringae pv. phaseolicola and was shown to be
      able to induce argK expression in M9 medium at 28 degrees C. These results
      indicate that argK expression is independent of temperature and is regulated
      directly by a compound resembling the inorganic moiety of phaseolotoxin.

PMID- 14679235
TI  - Esp-independent biofilm formation by Enterococcus faecalis.
AB  - Enterococcus faecalis is a gram-positive opportunistic pathogen known to form
      biofilms in vitro. In addition, this organism is often isolated from biofilms on
      the surfaces of various indwelling medical devices. However, the molecular
      mechanisms regulating biofilm formation in these clinical isolates are largely
      unknown. Recent work has suggested that a specific cell surface protein (Esp) of
      E. faecalis is critical for biofilm formation by this organism. However, in the
      same study, esp-deficient strains of E. faecalis were found to be capable of
      biofilm formation. To test the hypothesis that Esp is dispensable for biofilm
      formation by E. faecalis, we used microtiter plate assays and a chemostat-based
      biofilm fermentor assay to examine biofilm formation by genetically well-defined,
      non-Esp-expressing strains. Our results demonstrate that in vitro biofilm
      formation occurs, not only in the absence of esp, but also in the absence of the
      entire pathogenicity island that harbors the esp coding sequence. Using scanning
      electron microscopy to evaluate biofilms of E. faecalis OG1RF grown in the
      fermentor system, biofilm development was observed to progress through multiple
      stages, including attachment of individual cells to the substratum, microcolony
      formation, and maturation into complex multilayered structures apparently
      containing water channels. Microtiter plate biofilm analyses indicated that
      biofilm formation or maintenance was modulated by environmental conditions.
      Furthermore, our results demonstrate that expression of a secreted
      metalloprotease, GelE, enhances biofilm formation by E. faecalis. In summary, E.
      faecalis forms complex biofilms by a process that is sensitive to environmental
      conditions and does not require the Esp surface protein.

PMID- 14679236
TI  - Formation and composition of the Bacillus anthracis endospore.
AB  - The endospores of Bacillus anthracis are the infectious particles of anthrax.
      Spores are dormant bacterial morphotypes able to withstand harsh environments for
      decades, which contributes to their ability to be formulated and dispersed as a
      biological weapon. We monitored gene expression in B. anthracis during growth and
      sporulation using full genome DNA microarrays and matched the results against a
      comprehensive analysis of the mature anthrax spore proteome. A large portion
      (approximately 36%) of the B. anthracis genome is regulated in a growth phase
      dependent manner, and this regulation is marked by five distinct waves of gene
      expression as cells proceed from exponential growth through sporulation. The
      identities of more than 750 proteins present in the spore were determined by
      multidimensional chromatography and tandem mass spectrometry. Comparison of data
      sets revealed that while the genes responsible for assembly and maturation of the
      spore are tightly regulated in discrete stages, many of the components ultimately
      found in the spore are expressed throughout and even before sporulation,
      suggesting that gene expression during sporulation may be mainly related to the
      physical construction of the spore, rather than synthesis of eventual spore
      content. The spore also contains an assortment of specialized, but not obviously
      related, metabolic and protective proteins. These findings contribute to our
      understanding of spore formation and function and will be useful in the
      detection, prevention, and early treatment of anthrax. This study also highlights
      the complementary nature of genomic and proteomic analyses and the benefits of
      combining these approaches in a single study.

PMID- 14679237
TI  - Fine-tuning in regulation of Clp protein content in Bacillus subtilis.
AB  - Clp-controlled proteolysis in Bacillus subtilis seems to play a substantial role,
      particularly under stress conditions. Calibrated Western blot analyses were used
      to estimate the approximate numbers of heat-inducible Clp molecules within a
      single cell. According to these numbers, the different Clp ATPases do not seem to
      compete for the proteolytic subunit ClpP. Coimmunoprecipitation experiments
      revealed the predicted specific ClpX-ClpP, ClpC-ClpP, and ClpE-ClpP interactions.
      ClpE and ClpX are rapidly degraded in wild-type cells during permanent heat
      stress but remained almost stable in a clpP mutant, suggesting ClpP-dependent
      degradation. In particular, ClpCP appeared to be involved in the degradation of
      the short-lived ClpE ATPase, indicating a negative "autoregulatory" circuit for
      this particular Clp ATPase at the posttranslational level. Analysis of the half
      life of stress-inducible clp mRNAs during exponential growth and heat shock
      revealed precise regulation of the synthesis of each Clp protein at the
      posttranscriptional level as well to meet the needs of B. subtilis.

PMID- 14679238
TI  - pH-dependent catabolic protein expression during anaerobic growth of Escherichia
      coli K-12.
AB  - During aerobic growth of Escherichia coli, expression of catabolic enzymes and
      envelope and periplasmic proteins is regulated by pH. Additional modes of pH
      regulation were revealed under anaerobiosis. E. coli K-12 strain W3110 was
      cultured anaerobically in broth medium buffered at pH 5.5 or 8.5 for protein
      identification on proteomic two-dimensional gels. A total of 32 proteins from
      anaerobic cultures show pH-dependent expression, and only four of these proteins
      (DsbA, TnaA, GatY, and HdeA) showed pH regulation in aerated cultures. The levels
      of 19 proteins were elevated at the high pH; these proteins included metabolic
      enzymes (DhaKLM, GapA, TnaA, HisC, and HisD), periplasmic proteins (ProX, OppA,
      DegQ, MalB, and MglB), and stress proteins (DsbA, Tig, and UspA). High-pH
      induction of the glycolytic enzymes DhaKLM and GapA suggested that there was
      increased fermentation to acids, which helped neutralize alkalinity. Reporter lac
      fusion constructs showed base induction of sdaA encoding serine deaminase under
      anaerobiosis; in addition, the glutamate decarboxylase genes gadA and gadB were
      induced at the high pH anaerobically but not with aeration. This result is
      consistent with the hypothesis that there is a connection between the gad system
      and GabT metabolism of 4-aminobutanoate. On the other hand, 13 other proteins
      were induced by acid; these proteins included metabolic enzymes (GatY and AckA),
      periplasmic proteins (TolC, HdeA, and OmpA), and redox enzymes (GuaB, HmpA, and
      Lpd). The acid induction of NikA (nickel transporter) is of interest because E.
      coli requires nickel for anaerobic fermentation. The position of the NikA spot
      coincided with the position of a small unidentified spot whose induction in
      aerobic cultures was reported previously; thus, NikA appeared to be induced
      slightly by acid during aeration but showed stronger induction under anaerobic
      conditions. Overall, anaerobic growth revealed several more pH-regulated
      proteins; in particular, anaerobiosis enabled induction of several additional
      catabolic enzymes and sugar transporters at the high pH, at which production of
      fermentation acids may be advantageous for the cell.

PMID- 14679239
TI  - Surfaces of Spo0A and RNA polymerase sigma factor A that interact at the spoIIG
      promoter in Bacillus subtilis.
AB  - In Bacillus subtilis, the DNA binding protein Spo0A activates transcription from
      two classes of promoters, those used by RNA polymerase containing the primary
      sigma factor, sigma(A) (e.g., spoIIG), and those used by RNA polymerase
      containing the secondary sigma factor, sigma(H) (e.g., spoIIA). Several single
      amino acid substitutions in region 4 of sigma(A) define positions in sigma(A)
      that are specifically required for Spo0A-dependent promoter activation.
      Similarly, several single amino acid substitutions in Spo0A define positions in
      Spo0A that are required for sigma(A)-dependent promoter activation but not for
      other functions of Spo0A. It is unknown whether these amino acids in Spo0A
      interact directly with those in region 4 of sigma(A) or whether they interact
      with another subunit of RNA polymerase to effect promoter activation. Here we
      report the identification of a new amino acid in region 4 of sigma(A), arginine
      at position 355 (R355), that is involved in Spo0A-dependent promoter activation.
      To further investigate the role of R355, we used the coordinates of Spo0A and
      sigma region 4, each in complex with DNA, to build a model for the interaction of
      sigma(A) and Spo0A at the spoIIG promoter. We tested the model by examining the
      effects of amino acid substitutions in the putative interacting surfaces of these
      molecules. As predicted by the model, we found genetic evidence for interaction
      of R355 of sigma(A) with glutamine at position 221 of Spo0A. These results appear
      to define the surfaces of Spo0A and sigma(A) that directly interact during
      activation of the spoIIG promoter.

PMID- 14679240
TI  - Effect of the CopB auxiliary replication control system on stability of
      maintenance of Par(+) plasmid R1.
AB  - Plasmid R1 is a low-copy-number plasmid that is present at a level of about four
      or five copies per average cell. The copy number is controlled
      posttranscriptionally at the level of synthesis of the rate-limiting initiator
      protein RepA. In addition to this, R1 has an auxiliary system that derepresses a
      second promoter at low copy numbers, leading to increased repA mRNA synthesis.
      This promoter is normally switched off by a constitutively synthesized plasmid
      encoded repressor protein, CopB; in cells with low copy numbers, the
      concentration of CopB is low and the promoter is derepressed. Here we show that
      the rate of loss of a Par(+) derivative of the basic replicon of R1 increased
      about sevenfold when the cells contained a high concentration of the CopB protein
      formed from a compatible plasmid.

PMID- 14679241
TI  - Characterization of the 101-kilobase-pair megaplasmid pKB1, isolated from the
      rubber-degrading bacterium Gordonia westfalica Kb1.
AB  - The complete sequence of the circular 101,016-bp megaplasmid pKB1 from the cis
      1,4-polyisoprene-degrading bacterium Gordonia westfalica Kb1, which represents
      the first described extrachromosomal DNA of a member of this genus, was
      determined. Plasmid pKB1 harbors 105 open reading frames. The predicted products
      of 46 of these are significantly related to proteins of known function. Plasmid
      pKB1 is organized into three functional regions that are flanked by insertion
      sequence (IS) elements: (i) a replication and putative partitioning region, (ii)
      a putative metabolic region, and (iii) a large putative conjugative transfer
      region, which is interrupted by an additional IS element. Southern hybridization
      experiments revealed the presence of another copy of this conjugational transfer
      region on the bacterial chromosome. The origin of replication (oriV) of pKB1 was
      identified and used for construction of Escherichia coli-Gordonia shuttle
      vectors, which was also suitable for several other Gordonia species and related
      genera. The metabolic region included the heavy-metal resistance gene cadA,
      encoding a P-type ATPase. Expression of cadA in E. coli mediated resistance to
      cadmium, but not to zinc, and decreased the cellular content of cadmium in this
      host. When G. westfalica strain Kb1 was cured of plasmid pKB1, the resulting
      derivative strains exhibited slightly decreased cadmium resistance. Furthermore,
      they had lost the ability to use isoprene rubber as a sole source of carbon and
      energy, suggesting that genes essential for rubber degradation are encoded by
      pKB1.

PMID- 14679242
TI  - Inactivation of ompX causes increased interactions of type 1 fimbriated
      Escherichia coli with abiotic surfaces.
AB  - During the initial steps of biofilm formation, bacteria have to adapt to a major
      change in their environment. The adhesion-induced phenotypic changes in a type 1
      fimbriated Escherichia coli strain included reductions in the levels of several
      outer membrane proteins, one of which was identified as OmpX. Here, the
      phenotypes of mutant strains that differ at the ompX locus were studied with
      regard to adhesion, cell surface properties, and resistance to stress and
      antimicrobial compounds. The kinetics of adhesion were measured online by an
      extended quartz crystal microbalance technique for wild-type and mutant strains
      with a fimbriated or nonfimbriated background. Deletion of ompX led to
      significantly increased cell-surface contact in fimbriated strains but to
      decreased cell-surface contact in a nonfimbriated strain. Phenotypic
      characterization of the ompX mutant demonstrated that ompX interferes with proper
      regulation of cell surface structures that play a key role in mediating firm
      contact of the cell with a surface (i.e., type 1 fimbriae, flagellae, and
      exopolysaccharides). These phenotypic changes were accompanied by increased
      tolerance to several antibiotic compounds and sodium dodecyl sulfate. Based on
      these results, we propose that changes in the composition of outer membrane
      proteins during fimbria-mediated adhesion may be part of a coordinated adaptive
      response to the attached mode of growth.

PMID- 14679244
TI  - Identification of residues of the kid toxin involved in autoregulation of the
      parD system.
AB  - The toxin-antitoxin system parD (kis kid) of plasmid R1 is coregulated by the
      coordinated action of its two gene products. Here we describe the isolation and
      the in vivo characterization of three single-amino-acid changes in the Kid toxin,
      G4E, C74Y, and E91K, that affect the coregulatory activity but preserve the
      toxicity of the protein.

PMID- 14679243
TI  - Null mutation of HvrA compensates for loss of an essential relA/spoT-like gene in
      Rhodobacter capsulatus.
AB  - We report that a single relA/spoT-like gene exists on the Rhodobacter capsulatus
      chromosome, and its mutational loss is lethal. This gene could be mutated only
      under a mutational background of a null mutation in the nucleoid protein HvrA.
      This result suggests that there may be a direct link between HvrA-regulated
      promoters and the ppGpp-related stringent response.

PMID- 14679245
TI  - Necessity of meningococcal gamma-glutamyl aminopeptidase for Neisseria
      meningitidis growth in rat cerebrospinal fluid (CSF) and CSF-like medium.
AB  - The growth of a gamma-glutamyl aminopeptidase (GGT)-deficient Neisseria
      meningitidis strain was much slower than that of the parent strain in rat
      cerebrospinal fluid (CSF) and in a synthetic CSF-mimicking medium, and the growth
      failure was suppressed by the addition of cysteine. These results suggested that,
      in the environment of cysteine shortage, meningococcal GGT provided an advantage
      for meningococcal multiplication by supplying cysteine from environmental gamma
      glutamyl-cysteinyl peptides.

PMID- 14679246
TI  - Transcriptome analysis of the response of Pseudomonas aeruginosa to hydrogen
      peroxide.
AB  - Pseudomonas aeruginosa must often overcome a high concentration of oxidants to
      successfully infect the human host. We report here the results of a transcriptome
      profiling comparing cells treated with H(2)O(2) and untreated controls. The data
      indicate that the early response of P. aeruginosa to H(2)O(2) consists of an
      upregulation of protective mechanisms and a downregulation of primary metabolism.

PMID- 14679247
TI  - Production of heterologous and chimeric scaffoldins by Clostridium acetobutylicum
      ATCC 824.
AB  - Clostridium acetobutylicum ATCC 824 converts sugars and various polysaccharides
      into acids and solvents. This bacterium, however, is unable to utilize cellulosic
      substrates, since it is able to secrete very small amounts of cellulosomes. To
      promote the utilization of crystalline cellulose, the strategy we chose aims at
      producing heterologous minicellulosomes, containing two different cellulases
      bound to a miniscaffoldin, in C. acetobutylicum. A first step toward this goal
      describes the production of miniCipC1, a truncated form of CipC from Clostridium
      cellulolyticum, and the hybrid scaffoldin Scaf 3, which bears an additional
      cohesin domain derived from CipA from Clostridium thermocellum. Both proteins
      were correctly matured and secreted in the medium, and their various domains were
      found to be functional.

PMID- 14679248
TI  - A mother cell-specific class B penicillin-binding protein, PBP4b, in Bacillus
      subtilis.
AB  - The Bacillus subtilis genome encodes 16 penicillin-binding proteins (PBPs), some
      of which are involved in synthesis of the spore peptidoglycan. The pbpI (yrrR)
      gene encodes a class B PBP, PBP4b, and is transcribed in the mother cell by RNA
      polymerase containing sigma(E). Loss of PBP4b, alone and in combination with
      other sporulation-specific PBPs, had no effect on spore peptidoglycan structure.

PMID- 14679250
TI  - A piece of my mind. Passing through.

PMID- 14679249
TI  - An H(+)-coupled multidrug efflux pump, PmpM, a member of the MATE family of
      transporters, from Pseudomonas aeruginosa.
AB  - We cloned the gene PA1361 (we designated the gene pmpM), which seemed to encode a
      multidrug efflux pump belonging to the MATE family, of Pseudomonas aeruginosa by
      the PCR method using the drug-hypersensitive Escherichia coli KAM32 strain as a
      host. Cells of E. coli possessing the pmpM gene showed elevated resistance to
      several antimicrobial agents. We observed energy-dependent efflux of ethidium
      from cells possessing the pmpM gene. We found that PmpM is an H(+)-drug
      antiporter, and this finding is the first reported case of an H(+)-coupled efflux
      pump in the MATE family. Disruption and reintroduction of the pmpM gene in P.
      aeruginosa revealed that PmpM is functional and that benzalkonium chloride,
      fluoroquinolones, ethidium bromide, acriflavine, and tetraphenylphosphonium
      chloride are substrates for PmpM in this microorganism.

PMID- 14679251
TI  - Chronic kidney disease alarm bells rung.

PMID- 14679252
TI  - Health officials warn flu season could be severe.

PMID- 14679253
TI  - Surgeons "vote with their feet" for sentinel node biopsy for breast cancer
      staging.

PMID- 14679260
TI  - Acarbose for patients with hypertension and impaired glucose tolerance.

PMID- 14679261
TI  - Acarbose for patients with hypertension and impaired glucose tolerance.

PMID- 14679262
TI  - Acarbose for patients with hypertension and impaired glucose tolerance.

PMID- 14679264
TI  - Effect of exercise intensity on body composition.

PMID- 14679263
TI  - Acarbose for patients with hypertension and impaired glucose tolerance.

PMID- 14679265
TI  - Occupational safety of home health workers.

PMID- 14679266
TI  - Results of clinical trials sponsored by for-profit vs nonprofit entities.

PMID- 14679267
TI  - Results of clinical trials sponsored by for-profit vs nonprofit entities.

PMID- 14679268
TI  - Results of clinical trials sponsored by for-profit vs nonprofit entities.

PMID- 14679269
TI  - Premature application of trial results to clinical practice.

PMID- 14679270
TI  - Efalizumab for patients with moderate to severe plaque psoriasis: a randomized
      controlled trial.
AB  - CONTEXT: Because T-cell interactions are involved in the pathophysiology of
      psoriasis, therapy with a T-cell modulator may have beneficial effects on
      psoriasis severity and health-related quality of life (HRQL). OBJECTIVE: To
      assess the efficacy and safety of efalizumab, a T-cell modulator, in patients
      with plaque psoriasis. DESIGN, SETTING, AND PATIENTS: Phase 3 randomized, double
      blind, parallel-group, placebo-controlled trial involving 556 adult patients with
      stable, moderate to severe plaque psoriasis and conducted at 30 study centers in
      the United States and Canada between January and July 2002. INTERVENTIONS:
      Patients were randomly assigned in a 2:1 ratio to receive 12 weekly doses of
      subcutaneous efalizumab, 1 mg/kg (n = 369), or placebo equivalent (n = 187). MAIN
      OUTCOME MEASURES: At least 75% improvement on the Psoriasis Area and Severity
      Index (PASI-75); improvement on the overall Dermatology Life Quality Index
      (DLQI), Itching Visual Analog Scale (VAS), and Psoriasis Symptom Assessment (PSA)
      at week 12 vs baseline. RESULTS: Efalizumab-treated patients experienced
      significantly greater improvement on all end points than placebo-treated
      patients. Twenty-seven percent of efalizumab-treated patients achieved PASI-75 vs
      4% of the placebo group ( P<.001). Efalizumab-treated patients exhibited
      significantly greater mean percentage improvement than placebo-treated patients
      on the overall DLQI (47% vs 14%; P<.001), Itching VAS (38% vs -0.2%; P<.001), and
      PSA frequency and severity subscales (48% vs 18% and 47% vs 17%, respectively;
      P<.001 for both) at the first assessment point. Efalizumab was safe and well
      tolerated, with primarily mild to moderate adverse events. CONCLUSION: In this 12
      week study, efalizumab resulted in significant improvements in clinical end
      points, including physician-assessed and dermatology-specific patient-reported
      HRQL measures, in patients with moderate to severe plaque psoriasis.

PMID- 14679271
TI  - A practice-based intervention to enhance quality of care in the first 3 years of
      life: the Healthy Steps for Young Children Program.
AB  - CONTEXT: There is growing concern regarding the quality of health care available
      in the United States for young children, and specific limitations have been noted
      in developmental and behavioral services provided for children in the first 3
      years of life. OBJECTIVE: To determine the impact of the Healthy Steps for Young
      Children Program on quality of early childhood health care and parenting
      practices. DESIGN, SETTING, AND PARTICIPANTS: Prospective controlled clinical
      trial enrolling participants between September 1996 and November 1998 at 6
      randomization and 9 quasi-experimental sites across the United States.
      Participants were 5565 children enrolled at birth and followed up through age 3
      years. INTERVENTION: Incorporation of developmental specialists and enhanced
      developmental services into pediatric care in participants' first 3 years of
      life. MAIN OUTCOME MEASURES: Quality of care was operationalized across 4
      domains: effectiveness (eg, families received > or =4 Healthy Steps-related
      services or discussed >6 anticipatory guidance topics), patient-centeredness (eg,
      families were satisfied with care provided), timeliness (eg, children received
      timely well-child visits and vaccinations), and efficiency (eg, families remained
      at the practice for > or =20 months). Parenting outcomes included response to
      child misbehavior (eg, use of severe discipline) and practices to promote child
      development and safety (eg, mothers at risk for depression discussed their
      sadness with someone at the practice). RESULTS: Of the 5565 enrolled families,
      3737 (67.2%) responded to an interview at 30 to 33 months (usual care, 1716
      families; Healthy Steps, 2021 families). Families who participated in the Healthy
      Steps Program had greater odds of receiving 4 or more Healthy Steps-related
      services (for randomization and quasi-experimental sites, respectively: odds
      ratio [OR], 16.90 [95% confidence interval [CI], 12.78 to 22.34] and OR, 23.05
      [95% CI, 17.38 to 30.58]), of discussing more than 6 anticipatory guidance topics
      (OR, 8.56 [95% CI, 6.47 to 11.32] and OR, 12.31 [95% CI, 9.35 to 16.19]), of
      being highly satisfied with care provided (eg, someone in the practice went out
      of the way for them) (OR, 2.06 [95% CI, 1.64 to 2.58] and OR, 2.11 [95% CI, 1.72
      to 2.59]), of receiving timely well-child visits and vaccinations (eg, age
      appropriate 1-month visit) (OR, 1.98 [95% CI, 1.08 to 3.62] and OR, 2.11 [95% CI,
      1.16 to 3.85]), and of remaining at the practice for 20 months or longer (OR,
      2.02 [95% CI, 1.61 to 2.55] and OR, 1.75 [95% CI, 1.43 to 2.15]). They also had
      reduced odds of using severe discipline (eg, slapping in face or spanking with
      object) (OR, 0.82 [95% CI, 0.54 to 1.26] and OR, 0.67 [95% CI, 0.46 to 0.97]).
      Among mothers considered at risk for depression, those who participated in the
      Healthy Steps Program had greater odds of discussing their sadness with someone
      at the practice (OR, 0.95 [95% CI, 0.56 to 1.63] and OR, 2.82 [95% CI, 1.57 to
      5.08]). CONCLUSION: Universal, practice-based interventions can enhance quality
      of care for families of young children and can improve selected parenting
      practices.

PMID- 14679272
TI  - Cardiorespiratory fitness in young adulthood and the development of
      cardiovascular disease risk factors.
AB  - CONTEXT: Low cardiorespiratory fitness is an established risk factor for
      cardiovascular and total mortality; however, mechanisms responsible for these
      associations are uncertain. OBJECTIVE: To test whether low fitness, estimated by
      short duration on a maximal treadmill test, predicted the development of
      cardiovascular disease risk factors and whether improving fitness (increase in
      treadmill test duration between examinations) was associated with risk reduction.
      DESIGN, SETTING, AND PARTICIPANTS: Population-based longitudinal cohort study of
      men and women 18 to 30 years of age in the Coronary Artery Risk Development in
      Young Adults (CARDIA) study. Participants who completed the treadmill examination
      according to the Balke protocol at baseline were followed up from 1985-1986 to
      2000-2001. A subset of participants (n = 2478) repeated the exercise test in 1992
      1993. MAIN OUTCOME MEASURES: Incident type 2 diabetes, hypertension, the
      metabolic syndrome (defined according to National Cholesterol Education Program
      Adult Treatment Panel III), and hypercholesterolemia (low-density lipoprotein
      cholesterol > or =160 mg/dL [4.14 mmol/L]). RESULTS: During the 15-year study
      period, the rates of incident diabetes, hypertension, the metabolic syndrome, and
      hypercholesterolemia were 2.8, 13.0, 10.2, and 11.7 per 1000 person-years,
      respectively. After adjustment for age, race, sex, smoking, and family history of
      diabetes, hypertension, or premature myocardial infarction, participants with low
      fitness (<20th percentile) were 3- to 6-fold more likely to develop diabetes,
      hypertension, and the metabolic syndrome than participants with high fitness (>
      or =60th percentile), all P<.001. Adjusting for baseline body mass index
      diminished the strength of these associations to 2-fold (all P<.001). In
      contrast, the association between low fitness and hypercholesterolemia was modest
      (hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.1-1.7; P =.02) and
      attenuated to marginal significance after body mass index adjustment (P =.13).
      Improved fitness over 7 years was associated with a reduced risk of developing
      diabetes (HR, 0.4; 95% CI, 0.2-1.0; P =.04) and the metabolic syndrome (HR, 0.5;
      95% CI, 0.3-0.7; P<.001), but the strength and significance of these associations
      was reduced after accounting for changes in weight. CONCLUSIONS: Poor fitness in
      young adults is associated with the development of cardiovascular disease risk
      factors. These associations involve obesity and may be modified by improving
      fitness.

PMID- 14679273
TI  - Screening for proteinuria in US adults: a cost-effectiveness analysis.
AB  - CONTEXT: Chronic kidney disease is a growing public health problem. Screening for
      early identification could improve health but could also lead to unnecessary
      harms and excess costs. OBJECTIVE: To assess the value of periodic, population
      based dipstick screening for early detection of urine protein in adults with
      neither hypertension nor diabetes and in adults with hypertension. DESIGN,
      SETTING, AND POPULATION: Cost-effectiveness analysis using a Markov decision
      analytic model to compare a strategy of annual screening with no screening (usual
      care) for proteinuria at age 50 years followed by treatment with an angiotensin
      converting enzyme (ACE) inhibitor or an angiotensin II-receptor blocker (ARB).
      MAIN OUTCOME MEASURE: Cost per quality-adjusted life-year (QALY). RESULTS: For
      persons with neither hypertension nor diabetes, the cost-effectiveness ratio for
      screening vs no screening (usual care) was unfavorable (282 818 dollars per QALY;
      incremental cost of 616 dollars and a gain of 0.0022 QALYs per person). However,
      screening such persons beginning at age 60 years yielded a more favorable ratio
      (53 372 dollars per QALY). For persons with hypertension, the ratio was highly
      favorable (18 621 dollars per QALY; incremental cost of 476 dollars and a gain of
      0.03 QALYs per person). Cost-effectiveness was mediated by both chronic kidney
      disease progression and death prevention benefits of ACE inhibitor and ARB
      therapy. Influential parameters that might make screening for the general
      population more cost-effective include a greater incidence of proteinuria, age at
      screening (53 372 dollars per QALY for persons beginning screening at age 60
      years), or lower frequency of screening (every 10 years: 80 700 dollars per QALY
      at age 50 years; 6195 dollars per QALY at age 60 years; and 5486 dollars per QALY
      at age 70 years). CONCLUSIONS: Early detection of urine protein to slow
      progression of chronic kidney disease and decrease mortality is not cost
      effective unless selectively directed toward high-risk groups (older persons and
      persons with hypertension) or conducted at an infrequent interval of 10 years.

PMID- 14679274
TI  - Intra-articular hyaluronic acid in treatment of knee osteoarthritis: a meta
      analysis.
AB  - CONTEXT: Intra-articular hyaluronic acid is a US Food and Drug Administration
      approved treatment for knee osteoarthritis (OA); however, its efficacy is
      controversial. OBJECTIVE: To evaluate whether intra-articular hyaluronic acid is
      efficacious in treating knee OA. DATA SOURCES: We searched for human clinical
      trials in MEDLINE (1966 through February 2003) and the Cochrane Controlled Trials
      Register, using the search terms (osteoarthritis, osteoarthrosis, or degenerative
      arthritis) and (hyaluronic acid, Hyalgan, Synvisc, Artzal, Suplasyn, BioHy, or
      Orthovisc). We also hand searched manuscript bibliographies that met inclusion
      criteria, selected rheumatic disease journals, and abstracts from scientific
      meetings. STUDY SELECTION: Included were published or unpublished, English and
      non-English, single- or double-blinded, randomized controlled trials comparing
      intra-articular hyaluronic acid with intra-articular placebo injection for the
      treatment of knee OA. Trials also were required to have extractable data on pain
      reported by 1 of the outcome measures recommended by the Osteoarthritis Research
      Society. DATA EXTRACTION: Two reviewers independently performed data extraction
      using standardized data forms. For each trial, we calculated an effect size
      (small-effect sizes, 0.2-0.5; large-effect sizes, 1.0-1.8, equivalent to a total
      knee replacement). We used a random-effects model to pool study results, the
      Cochrane Q test to evaluate heterogeneity, and a funnel plot and the Egger test
      to evaluate publication bias. DATA SYNTHESIS: The overall dropout rate in the 22
      selected trials was 12.4%. The pooled effect size for hyaluronic acid was 0.32
      (95% confidence interval [CI], 0.17-0.47). There was significant heterogeneity
      among studies (P<.001). Two outlier trials, both evaluating the highest-molecular
      weight hyaluronic acid, had effect sizes in excess of 1.5. However, the third
      trial of the same compound showed a nearly null effect. When the 3 trials of this
      compound were removed, heterogeneity was no longer significant (P =.58), and the
      pooled effect size for intra-articular hyaluronic acid decreased to 0.19 (95% CI,
      0.10-0.27). There was evidence of publication bias with an asymmetric funnel
      plot, a positive Egger test, and identification of 2 unpublished trials whose
      pooled effect size was 0.07 (95% CI, - 0.15 to 0.28). CONCLUSION: Intra-articular
      hyaluronic acid has a small effect when compared with an intra-articular placebo.
      The presence of publication bias suggests even this effect may be overestimated.
      Compared with lower-molecular-weight hyaluronic acid, the highest-molecular
      weight hyaluronic acid may be more efficacious in treating knee OA, but
      heterogeneity of these studies limits definitive conclusions.

PMID- 14679275
TI  - Strengthening the supply of routinely recommended vaccines in the United States:
      recommendations from the National Vaccine Advisory Committee.
AB  - Between late 2000 and the spring of 2003, the United States experienced shortages
      of vaccines against 8 of 11 preventable diseases in children. In response, the
      Department of Health and Human Services requested that the National Vaccine
      Advisory Committee (NVAC) make recommendations on strengthening the supply of
      routinely recommended vaccines. The NVAC appointed a Working Group to identify
      potential causes of vaccine supply shortages, develop strategies to alleviate or
      prevent shortages, and enlist stakeholders to consider the applicability and
      feasibility of these strategies. The NVAC concluded that supply disruptions are
      likely to continue to occur. Strategies to be implemented in the immediate future
      include expansion of vaccine stockpiles, increased support for regulatory
      agencies, maintenance and strengthening of liability protections, improved
      communication among stakeholders, increased availability of public information,
      and a campaign to emphasize the benefits of vaccination. Strategies requiring
      further study include evaluation of appropriate financial incentives to
      manufacturers and streamlining the regulatory process without compromising safety
      or efficacy.

PMID- 14679276
TI  - Sexual activity in patients with angina.

PMID- 14679277
TI  - A promising step forward in psoriasis therapy.

PMID- 14679278
TI  - Optimizing the health and development of children.

PMID- 14679279
TI  - JAMA patient page. Psoriasis.

PMID- 14679280
TI  - The effect of Integrated Management of Childhood Illness on observed quality of
      care of under-fives in rural Tanzania.
AB  - Integrated Management of Childhood Illness (IMCI) has been adopted by over 80
      countries as a strategy for reducing child mortality and improving child health
      and development. It includes complementary interventions designed to address the
      major causes of child mortality at community, health facility, and health system
      levels. The Multi-Country Evaluation of IMCI Effectiveness, Cost and Impact (IMCI
      MCE) is a global evaluation to determine the impact of IMCI on health outcomes
      and its cost-effectiveness. The MCE is coordinated by the Department of Child and
      Adolescent Health and Development of the World Health Organization. MCE studies
      are under way in Bangladesh, Brazil, Peru, Tanzania and Uganda. In Tanzania, the
      IMCI-MCE study uses a non-randomized observational design comparing four
      neighbouring districts, two of which have been implementing IMCI in conjunction
      with evidence-based planning and expenditure mapping at district level since
      1997, and two of which began IMCI implementation in 2002. In these four
      districts, child health and child survival are documented at household level
      through cross-sectional, before-and-after surveys and through longitudinal
      demographic surveillance respectively. Here we present results of a survey
      conducted in August 2000 in stratified random samples of government health
      facilities to compare the quality of case-management and health systems support
      in IMCI and comparison districts. The results indicate that children in IMCI
      districts received better care than children in comparison districts: their
      health problems were more thoroughly assessed, they were more likely to be
      diagnosed and treated correctly as determined through a gold-standard re
      examination, and the caretakers of the children were more likely to receive
      appropriate counselling and reported higher levels of knowledge about how to care
      for their sick children. There were few differences between IMCI and comparison
      districts in the level of health system support for child health services at
      facility level. This study suggests that IMCI, in the presence of a decentralized
      health system with practical health system planning tools, is feasible for
      implementation in resource-poor countries and can lead to rapid gains in the
      quality of case-management. IMCI is therefore likely to lead to rapid gains in
      child survival, health and development if adequate coverage levels can be
      achieved and maintained.

PMID- 14679281
TI  - Cost efficiency in maternal and child health and family planning service delivery
      in Bangladesh: implications for NGOs.
AB  - The main goal of the health reform programme recently initiated in Bangladesh is
      to reduce costs and improve cost efficiency of the service delivery systems, and
      thereby ensure the sustainable provision of essential health and family planning
      services. With significant dependency on external funding, attainment of this
      objective is more critical for non-government organization (NGO) programmes. The
      paper analyzes costs of the NGO service delivery systems for maternal and child
      health and family planning, and identifies areas for increasing efficiency,
      especially through reducing labour costs and increasing service outputs. The
      operations research on cost analyses was conducted within the health and family
      planning programmes of a leading NGO, using the 'ingredients approach'. The
      findings demonstrated a significantly high proportion of personnel costs in field
      (outreach) service delivery systems, ranging between 70-85%. More than two-thirds
      of the working time of providers was spent on support activities, personal
      preoccupations and idle time. Simulations of various cost reduction options
      showed that considerable efficiency gains were possible through the combined
      effects of lowering personnel costs for field activities, increasing service
      outputs at the clinics, and ensuring more efficient use of providers' time.
      However, these factors, neither separately nor in combination, resulted in any
      substantive decrease for certain clinic services (e.g. antenatal care), implying
      the need to subsidize these services. The findings of the operations research
      indicated that cost analyses could be an effective decision-making tool for NGOs
      in developing cost-efficient service delivery strategies.

PMID- 14679282
TI  - Access to health care for all? User fees plus a Health Equity Fund in Sotnikum,
      Cambodia.
AB  - User fees in health services are a source of much debate because of their
      potential risk of negative effects on access to health care for the poor. A
      Health Equity Fund that identifies the poor and pays on their behalf may be an
      alternative to generally ineffective fee exemption policies. This paper presents
      the experience of such a Health Equity Fund, managed by a local non-governmental
      organization, in Sotnikum, Cambodia. It describes the results of the first 2
      years of operations, investigates the constraints to equitable access to the
      district hospital and the effects of the Health Equity Fund on these constraints.
      The Health Equity Fund supported 16% of hospitalized patients. We found four
      major constraints to access: financial, geographical, informational and intra
      household. The results of the study show that the Health Equity Fund effectively
      improves financial access for the poor, but that the poor continue to face many
      constraints for timely access. The study also found that the Health Equity Fund
      as set up in Sotnikum was very cost-effective, with minimal leakage to non-poor.
      Health Equity Funds managed by a local non-governmental organization seem to
      constitute a promising channel for donors who want to invest in poverty
      reduction. However, further research and experimentation are recommended in
      different contexts and with different set-ups.

PMID- 14679283
TI  - Primary level psychological services in South Africa: can a new psychological
      professional fill the gap?
AB  - Care for common mental health problems in medium-resourced countries has been
      conceptualized by the World Health Organization as needing to be provided by
      primary health care personnel, in particular primary health care nurses. This
      study, which comprised a file audit of a psychological referral service at
      primary level in South Africa, suggests that in contexts where specialized
      psychological services are lacking, the demand for mental health services
      includes that of psychometric assessment services for mental retardation and/or
      scholastic problems. It is argued that in these contexts, third generation health
      systems reforms should be applied to the provision of care for more common mental
      health problems as well as mental retardation and/or scholastic problems in
      medium-resourced countries. This would require the insertion of a 'package'
      comprised of both psychological assessment and intervention services. It is
      suggested that in South Africa, such a 'package' could be provided by the new
      professional category of 'counsellor', which the Professional Board of Psychology
      of the South African Health Professions Council has recently accredited.

PMID- 14679284
TI  - Assessing the performance of primary health centres under decentralized
      government in Kerala, India.
AB  - CONTEXT: Kerala's government health-care system functions relatively well
      compared with other Indian States, but utilization levels are decreasing due to
      lack of essential facilities. The opportunity cost of seeking medical care from
      the government sector is high, even for the poor, with 60-70% of the poor seeking
      care from the private sector and spending disproportionately on health care
      (about 40% of income compared with 2.4% by the rich). In 1996, the Kerala
      government brought primary health centres (PHCs) under the control of local
      governments (panchayats). OBJECTIVE: To provide an approach to assess PHC
      performance under decentralized government. METHODS: The study was conducted in
      three stages. The first stage included all 990 village panchayats in Kerala. The
      second stage covered 10 panchayats (their respective 10 PHCs and 65 sub-centres)
      occupying the top five and bottom five ranks in terms of resource allocation to
      health. Two panchayats (their respective PHCs and sub-centres), one each from the
      top five and the bottom five, were chosen for the third stage. Published and
      unpublished government data, panchayat development reports, panchayat and PHC
      records, facility checklist, and key informant and client exit interviews were
      used for data collection. FINDINGS: Panchayats in Kerala allocated a lower
      proportion of resources to health than that allocated by the state government
      prior to decentralization; while panchayat resources grew at an annual rate of
      30.7%, health resources grew at 7.9%. PHCs were funded to the extent of 0.7-2.7%
      of the total cost. An additional 2% in PHC resources was associated with improved
      patient load (63.5%), cost-effectiveness (50.8%), medicine supply (49.4%),
      information (32.8%) and patient satisfaction (12.7%). An annual increase of
      US$940 in PHC resources would help to extend primary care facilities to 3000
      (15.5%) more users. CONCLUSION: Decentralization brought no significant change to
      the health sector. Active panchayat support to PHCs existed in only a few places,
      but wherever it was present, the result was positive. Kerala should find an
      alternative strategy to channel panchayats towards health before health loses its
      battle for resources.

PMID- 14679285
TI  - The Global Fund to fight AIDS, Tuberculosis and Malaria (GFATM).

PMID- 14679286
TI  - Obstetric audit in resource-poor settings: lessons from a multi-country project
      auditing 'near miss' obstetrical emergencies.
AB  - This paper outlines the practical steps involved in setting up and running multi
      professional, in-depth case reviews of 'near miss' obstetrical complications. It
      draws on lessons learned in 12 referral hospitals in Benin, Cote d'Ivoire, Ghana
      and Morocco. A range of feasibility indicators are presented which measured the
      implementation and frequency of audit activities, the quality of participation,
      adherence to the planned protocol for the near-miss audits, the quality of audit
      discussions and the sustainability of the project. Although the principles of the
      audit approach were well accepted and implemented everywhere, near-miss audits
      appeared most successful in first referral level hospitals. Contextual factors
      that determine the successful implementation of near-miss audit include staff
      finding adequate time for audit activities, financial incentives to groups rather
      than individuals, involvement of senior staff and hospital managers, the ease of
      communication in smaller units, the employment of social workers for the
      incorporation of women's views at audits, and the strength of external support
      provided by the research team. The poor quality of information recorded in case
      notes was recognized everywhere as a deficiency, but did not present a major
      obstacle to effective case reviews. Ownership and leadership within the hospital,
      more easily achieved in the first-level referral hospitals, were probably the
      most important determinants of successful implementation. Sustainability requires
      a commitment to audit from policy makers and managers at higher levels of the
      health system and some devolution of resources for implementing recommendations.

PMID- 14679288
TI  - Meeting report: cellular dependence--old concept, new mechanisms.
AB  - Programmed cell death occurs in response to both the presence of various
      extracellular factors and the lack of specific factors. Receptors that can
      mediate cell death in the absence of ligand binding are called dependence
      receptors, and they were the topic of the meeting held during the summer of 2003
      in Fondation des Treilles, France. Not only is progress being made in the
      identification of new dependence receptors, but the partners that carry out this
      "negative" signal are also coming to light. With several of the receptors
      implicated in various human developmental disorders or disease states, gaining an
      understanding of the molecular mechanisms controlling dependence receptor
      mediated cell death has clear clinical relevance.

PMID- 14679289
TI  - Finding partners: emerging protein interaction technologies applied to signaling
      networks.
AB  - Signal transduction pathways play essential roles in cell differentiation,
      proliferation, and survival. Their precise regulation is achieved through
      specific protein-protein interactions that mediate the assembly of protein
      complexes in response to different signals. Disturbances of the normal protein
      protein interactions within signaling pathways can lead to many diseases,
      including cancer. In this review, Stagljar aims to highlight the emerging protein
      interaction technologies that are advancing the field of signal transduction.
      These approaches include stable isotope labeling by amino acids in cell culture,
      SH2 profiling, target-assisted iterative screening, and the split-ubiquitin
      membrane yeast two-hybrid system. Although still at an early stage, these
      technologies show promise as useful methods for the characterization of novel
      components of various signal transduction pathways.

PMID- 14679290
TI  - Membrane recognition and targeting by lipid-binding domains.
AB  - Modular domains that recognize and target intracellular membranes play a critical
      role in the assembly, localization, and function of signaling and trafficking
      complexes in eukaryotic cells. Large domain families, including PH, FYVE, PX,
      PHD, and C2 domains, combine specific, nonspecific, and multivalent interactions
      to achieve selective membrane targeting. Despite structural and functional
      diversity, general features of lipid recognition are evident in the various
      membrane-targeting mechanisms.

PMID- 14679291
TI  - EH and UIM: endocytosis and more.
AB  - Exogenously and endogenously originated signals are propagated within the cell by
      functional and physical networks of proteins, leading to numerous biological
      outcomes. Many protein-protein interactions take place between binding domains
      and short peptide motifs. Frequently, these interactions are inducible by
      upstream signaling events, in which case one of the two binding surfaces may be
      created by a posttranslational modification. Here, we discuss two protein
      networks. One, the EH-network, is based on the Eps15 homology (EH) domain, which
      binds to peptides containing the sequence Asp-Pro-Phe (NPF). The other, which we
      define as the monoubiquitin (mUb) network, relies on monoubiquitination, which is
      emerging as an important posttranslational modification that regulates protein
      function. Both networks were initially implicated in the control of plasma
      membrane receptor endocytosis and in the regulation of intracellular trafficking
      routes. The ramifications of these two networks, however, appear to extend into
      many other aspects of cell physiology as well, such as transcriptional
      regulation, actin cytoskeleton remodeling, and DNA repair. The focus of this
      review is to integrate available knowledge of the EH- and mUb networks with
      predictions of genetic and physical interactions stemming from functional
      genomics approaches.

PMID- 14679292
TI  - The effect of the knee adduction moment on tibial cartilage volume and bone size
      in healthy women.
AB  - OBJECTIVES: There is considerable evidence that an abnormally high knee adductor
      moment is a characteristic of the gait patterns in people with knee
      osteoarthritis (OA). The aim of this study was to examine the relationship
      between the peak knee adduction moment during the early and late stance phases of
      gait, and medial and lateral tibial bone size and cartilage volume in healthy
      women. METHODS: Three-dimensional Vicon gait analyses and magnetic resonance
      imaging (MRI) were performed on 20 healthy women without knee OA. The external
      knee adduction moment was correlated with medial and lateral tibial bone size and
      cartilage volume for the dominant leg. RESULTS: The knee adduction moment
      significantly correlated with the bone size of the medial tibial plateau (r =
      0.63, P < 0.005), but was not related to the bone size of the lateral plateau. No
      relationship was observed between the knee adduction moment and medial or lateral
      tibial cartilage volume. CONCLUSIONS: Although the knee adduction moment was
      positively associated with the bone size of the medial tibial plateau, it
      appeared to have little effect on cartilage volume in that compartment in healthy
      women. It may be that the effect of the knee adduction moment differs in healthy
      subjects compared with those with established knee OA.

PMID- 14679293
TI  - Tissue production of pro-inflammatory cytokines (IL-1beta, TNFalpha and IL-6)
      correlates with the intensity of the systemic inflammatory response and with
      corticosteroid requirements in giant-cell arteritis.
AB  - OBJECTIVES: To investigate proinflammatory cytokine expression in temporal
      arteries from patients with giant-cell arteritis (GCA) and to analyse its
      relationship with the intensity of the initial systemic inflammatory reaction and
      response to corticosteroid therapy. METHODS: Quantification of interleukin-1beta
      (IL-1beta), tumor necrosis factor alpha (TNFalpha), and interleukin-6 (IL-6) mRNA
      by real-time quantitative PCR in temporal artery samples from 36 patients with
      biopsy-proven GCA and 11 controls. Immunohistochemical detection of IL-1beta,
      TNFalpha, and IL-6 in temporal artery sections from 74 patients with GCA and 15
      controls. Clinical and biochemical parameters of inflammation as well as the time
      (weeks) required to reach a maintenance prednisone dose <10 mg/day were recorded.
      RESULTS: IL-1beta (13.8 +/- 2.5 vs 5.4 +/- 1.3 relative units, P = 0.012) and IL
      6 transcripts (34 +/- 13.7 vs 7.8 +/- 4.5 relative units, P = 0.034) were
      significantly more abundant in patients with a strong systemic inflammatory
      response compared with those with no inflammatory parameters. Immunohistochemical
      scores for IL-1beta (2.7 +/- 0.3 vs 1.9 +/- 0.2, P = 0.018), TNFalpha (3.2 +/-
      0.2 vs 2.4 +/- 0.3, P = 0.028) and IL-6 (3 +/- 0.2 vs 2.1 +/- 0.3, P = 0.023)
      were also significantly higher in patients with strong systemic inflammatory
      reaction. A significant correlation was found between the amount of tissue
      TNFalpha mRNA and the time required to reach a maintenance dose of prednisone <10
      mg/day (r = 0.586, P = 0.001). CONCLUSION: GCA patients with a strong systemic
      inflammatory response, who have been previously shown to be more resistant to
      corticosteroid therapy, have elevated tissue expression of proinflammatory
      cytokines IL-1beta, TNFalpha and IL-6. High production of TNFalpha is associated
      with longer corticosteroid requirements.

PMID- 14679294
TI  - Expression of KIR and C-type lectin receptors in Behcet's disease.
AB  - OBJECTIVE: Behcet's disease (BD) is a multisystemic disorder with a possible
      underlying pathology of immune-mediated vasculitis. Genetic susceptibility
      associated with HLA-B*51 and B*2702 has been implicated in its pathogenesis.
      Considering the recently defined regulatory mechanisms of NK cells through HLA
      class I binding receptors, we hypothesized that interactions of NK and T cells
      through the NK receptors may be important in the pathogenesis of BD. METHODS: The
      impact of different expression patterns of HLA-recognizing receptors on NK or T
      cells was analysed in 51 patients with BD and 32 healthy controls. We used flow
      cytometry to investigate the expression of KIR3DL1 from the polymorphic killer
      immunoglobulin-like receptor (KIR) family, which binds a shared HLA-Bw4 motif on
      HLA-B51 and *2702 alleles, and CD94 from the conserved C-type lectin receptor
      family, which binds HLA-E. Thirty-three of the BD patients and 19 of the controls
      carried the same HLA-Bw4 motif. RESULTS: CD3(+) T cells were increased in
      patients with BD compared with controls (81 vs 75%, P = 0.001), whereas the NK
      cells did not show any difference between the two groups. Increased expression of
      CD94 in BD was observed on CD16(+)CD56(+) cells (66 vs 57, P = 0.04) and on
      CD3(+) (7.7 vs 4.0, P < 0.001) and CD3(+)CD56(+) (44 vs 35, P = 0.02) T cells.
      KIR3DL1 expression on the NK and T cells was not statistically different between
      the two groups. No effect of HLA-Bw4 motif was observed on the expression of CD94
      and KIR3DL1 in both the patients and the controls. CONCLUSION: The absence of a
      correlation between KIR3DL1 expression and HLA-Bw4 motif confirms previous work
      reporting that the expression of these molecules is regulated separately.
      Increased expression of CD94 may suggest that NK receptors play a pathogenic or
      regulatory role in BD.

PMID- 14679295
TI  - The health assessment questionnaire (HAQ) is strongly predictive of good outcome
      in early diffuse scleroderma: results from an analysis of two randomized
      controlled trials in early diffuse scleroderma.
AB  - OBJECTIVE: Scoring poorly on the health assessment questionnaire (HAQ) has
      recently been shown to be a strong predictor of morbidity and mortality in
      rheumatoid arthritis (RA), while a good HAQ score is predictive of a better
      outcome. In patients presenting with early diffuse scleroderma prognosis is
      variable. Our goal was to determine possible baseline predictors of future good
      outcomes. METHODS: We used the raw data from two randomized controlled trials
      (RCTs) in early diffuse scleroderma: methotrexate (Pope et al.) and D
      penicillamine (Clements et al.). Subjects in the methotrexate trial were divided
      into the following groups: (1) those with at least 20% improvement in the primary
      outcome measurements [patient global assessment, physician global assessment,
      UCLA skin tethering score, modified Rodnan skin score (MRSS), DLCO as % predicted
      and HAQ disability] at 1 yr vs (2) the others. Baseline factors (including age,
      gender, skin scores, physician and patient global assessments, HAQ disability and
      pain scores, DLCO and physical parameters) were analysed to find baseline
      variables strongly correlated with later improvement. These variables were
      explored in the D-penicillamine trial to determine if (in a separate trial) they
      were still predictive of improved outcome at 1 and 2 yr. Adjusted models were
      used to find baseline predictors of good outcome. The median HAQ-DI was 1.3
      (methotrexate) and 1.0 (D-penicillamine). RESULTS: A baseline HAQ disability
      score of less than the median was predictive of at least a 20% improvement at 1
      and 2 yr with odds ratios of 1.77 to 5.05, in four of the five outcome
      measurements (in both groups); with strongly significant P values for 3 of 5
      outcomes (UCLA skin score, MRSS, patient global skin score; P<0.02) from the
      methotrexate study group. These three outcomes were strongly correlated with
      improvement (r between 0.25 and 0.35). Although data from the D-penicillamine
      trial were less convincing, in both trials the less than median HAQ-DI and HAQ
      pain scores showed a stronger association with improved outcome, more so than
      age, gender, skin score and baseline global assessment. CONCLUSION: A low
      baseline HAQ (defined as less than the median HAQ score) is predictive of
      improved outcome in diffuse scleroderma at 1 and 2 yr.

PMID- 14679296
TI  - Apoptosis a relevant therapeutic target in rheumatoid arthritis?

PMID- 14679297
TI  - IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient
      mouse embryonic fibroblasts.
AB  - Virus infection, double-stranded RNA, and lipopolysaccharide each induce the
      expression of genes encoding IFN-alpha and -beta and chemokines, such as RANTES
      (regulated on activation, normal T cell expressed and secreted) and IP-10 (IFN
      gamma inducible protein 10). This induction requires the coordinate activation of
      several transcription factors, including IFN-regulatory factor 3 (IRF3). The
      signaling pathways leading to IRF3 activation are triggered by the binding of
      pathogen-specific products to Toll-like receptors and culminate in the
      phosphorylation of specific serine residues in the C terminus of IRF3. Recent
      studies of human cell lines in culture have implicated two noncanonical IkappaB
      kinase (IKK)-related kinases, IKK-epsilon and Traf family member-associated NF
      kappaB activator (TANK)-binding kinase 1 (TBK1), in the phosphorylation of IRF3.
      Here, we show that purified recombinant IKK-epsilon and TBK1 directly
      phosphorylate the critical serine residues in IRF3. We have also examined the
      expression of IRF3-dependent genes in mouse embryonic fibroblasts (MEFs) derived
      from Tbk1(-/-) mice, and we show that TBK1 is required for the activation and
      nuclear translocation of IRF3 in these cells. Moreover, Tbk1(-/-) MEFs show
      marked defects in IFN-alpha and -beta, IP-10, and RANTES gene expression after
      infection with either Sendai or Newcastle disease viruses or after engagement of
      the Toll-like receptors 3 and 4 by double-stranded RNA and lipopolysaccharide,
      respectively. Finally, TRIF (TIR domain-containing adapter-inducing IFN-beta),
      fails to activate IRF3-dependent genes in Tbk1(-/-) MEFs. We conclude that TBK1
      is essential for IRF3-dependent antiviral gene expression.

PMID- 14679298
TI  - Evaluation of common gene expression patterns in the rat nervous system.
AB  - In the postgenomic era, integrating data obtained from array technologies (e.g.,
      oligonucleotide microarrays) with published information on eukaryotic genomes is
      beginning to yield biomarkers and therapeutic targets that are key for the
      diagnosis and treatment of disease. Nevertheless, identifying and validating
      these drug targets has not been a trivial task. Although a plethora of
      bioinformatics tools and databases are available, major bottlenecks for this
      approach reside in the interpretation of vast amounts of data, its integration
      into biologically representative models, and ultimately the identification of
      pathophysiologically and therapeutically useful information. In the field of
      neuroscience, accomplishing these goals has been particularly challenging because
      of the complex nature of nerve tissue, the relatively small adaptive nature of
      induced-gene expression changes, as well as the polygenic etiology of most
      neuropsychiatric diseases. This report combines published data sets from multiple
      transcript profiling studies that used GeneChip microarrays to illustrate a
      postanalysis approach for the interpretation of data from neuroscience microarray
      studies. By defining common gene expression patterns triggered by diverse events
      (administration of psychoactive drugs and trauma) in different nerve tissues
      (telencephalic brain areas and spinal cord), we broaden the conclusions derived
      from each of the original studies. In addition, the evaluation of the identified
      overlapping gene lists provides a foundation for generating hypotheses relating
      alterations in specific sets of genes to common physiological processes. Our
      approach demonstrates the significance of interpreting transcript profiling data
      within the context of common pathways and mechanisms rather than specific to a
      given tissue or stimulus. We also highlight the use of gene expression patterns
      in predictive biology (e.g., in toxicogenomics) as well as the utility of
      combining data derived from multiple microarray studies that examine diverse
      biological events for a broader interpretation of data from a particular
      microarray study.

PMID- 14679299
TI  - Life-long reduction in MnSOD activity results in increased DNA damage and higher
      incidence of cancer but does not accelerate aging.
AB  - Mice heterozygous for the Sod2 gene (Sod2+/- mice) have been used to study the
      phenotype of life-long reduced Mn-superoxide dismutase (MnSOD) activity. The
      Sod2+/- mice have reduced MnSOD activity (50%) in all tissues throughout life.
      The Sod2+/- mice have increased oxidative damage as demonstrated by significantly
      elevated levels of 8-oxo-2-deoxyguanosine (8oxodG) in nuclear DNA in all tissues
      of Sod2+/- mice studied. The levels of 8oxodG in nuclear DNA increased with age
      in all tissues of Sod2+/- and wild-type (WT) mice, and at 26 mo of age, the
      levels of 8oxodG in nuclear DNA were significantly higher (from 15% in heart to
      over 60% in liver) in the Sod2+/- mice compared with WT mice. The level of 8oxodG
      was also higher in mitochondrial DNA isolated from liver and brain in Sod2+/-
      mice compared with WT mice. The increased oxidative damage to DNA in the Sod2+/-
      mice is associated with a 100% increase in tumor incidence (the number of mice
      with tumors) in old Sod2+/- mice compared with the old WT mice. However, the life
      spans (mean and maximum survival) of the Sod2+/- and WT mice were identical. In
      addition, biomarkers of aging, such as cataract formation, immune response, and
      formation of glycoxidation products carboxymethyl lysine and pentosidine in skin
      collagen changed with age to the same extent in both WT and Sod2+/- mice. Thus
      life-long reduction of MnSOD activity leads to increased levels of oxidative
      damage to DNA and increased cancer incidence but does not appear to affect aging.

PMID- 14679300
TI  - Genetic architecture of fast- and slow-twitch skeletal muscle weight in 200-day
      old mice of the C57BL/6J and DBA/2J lineage.
AB  - The aim of the study was to explore the genetic architecture influencing weight
      of fast- and slow-twitch skeletal muscles. The weights of the slow-twitch soleus,
      the mixed gastrocnemius, the fast-twitch tibialis anterior (TA), and extensor
      digitorum longus (EDL) muscles were 11-34% greater (P < 0.001) in 200-day-old
      C57BL/6J (B6) than in DBA/2J (D2) mice. Male muscles were 13-28% larger than
      female (P < 1 x 10(-5), no strain by sex interaction). The sex-related difference
      in muscle weight, however, varied significantly among the 23 derivative BXD
      recombinant inbred (RI) strains (strain by sex interaction for soleus, P < 0.01;
      TA, P < 1 x 10(-4); EDL, not significant; and gastrocnemius, P < 0.001).
      Quantitative trait loci (QTL) affecting muscle weight were mapped in an F2
      intercross of B6 and D2 mice (B6D2F2) and BXD RIs. A total of 10 autosomal,
      muscle-specific, but not muscle-type-specific, QTL, explaining a total of 5.4,
      7.7, 22.9, and 8.6% of phenotypic variance for soleus, TA, EDL, and gastrocnemius
      muscles, respectively, were found across chromosomes 1 (Chr 1), 2, 3 (female
      specific), 5 (two), 6, 7, 8, and 9 in B6D2F2 mice. The QTL on Chr 8 for EDL and
      the female-specific QTL on Chr 3 for gastrocnemius muscles were statistically
      significant, but the remaining QTL were at the suggestive level of statistical
      significance. Ten QTL on Chr 1, 2, 4, 5, 7, 8, 14, 17 (two), and 19 were
      identified in BXD RIs. Half of the QTL in BXD RIs had pleiotropic effects and
      were at the suggestive level of significance (except for the significant QTL for
      gastrocnemius muscle on Chr 17). The B6D2F2 nominated QTL on Chr 8 for EDL weight
      was validated in BXD RIs (P < 0.03). Support intervals for the QTL on Chr 1 and 5
      overlapped between B6D2F2 and BXD RIs. An epistatic interaction between markers
      on Chr 1 and 17 affected gastrocnemius weight in BXD RIs. The interaction was
      not, however, validated in the B6D2F2 population. Our results indicate that the
      differences in muscle weight in the B6 and D2 segregating populations were the
      outcome of a polygenic system, with each factor contributing a small amount to
      the phenotypic variance and the genetic architecture affecting muscle weight was
      muscle specific, but not muscle-type specific, and in some instances sex
      specific.

PMID- 14679301
TI  - Mouse cardiac surgery: comprehensive techniques for the generation of mouse
      models of human diseases and their application for genomic studies.
AB  - Mouse models mimicking human diseases are important tools in trying to understand
      the underlying mechanisms of many disease states. Several surgical models have
      been described that mimic human myocardial infarction (MI) and pressure-overload
      induced cardiac hypertrophy. However, there are very few detailed descriptions
      for performing these surgical techniques in mice. Consequently, the number of
      laboratories that are proficient in performing cardiac surgical procedures in
      mice has been limited. Microarray technologies measure the expression of
      thousands of genes simultaneously, allowing for the identification of genes and
      pathways that may potentially be involved in the disease process. The statistical
      analysis of microarray experiments is highly influenced by the amount of
      variability in the experiment. To keep the number of required independent
      biological replicates and the associated costs of the study to a minimum, it is
      critical to minimize experimental variability by optimizing the surgical
      procedures. The aim of this publication was to provide a detailed description of
      techniques required to perform mouse cardiac surgery, such that these models can
      be utilized for genomic studies. A description of three major surgical procedures
      has been provided: 1) aortic constriction, 2) pulmonary artery banding, 3) MI
      (including ischemia-reperfusion). Emphasis has been placed on technical
      procedures with the inclusion of thorough descriptions of all equipment and
      devices employed in surgery, as well as the application of such techniques for
      expression profiling studies. The cardiac surgical techniques described have
      been, and will continue to be, important for elucidating the molecular mechanisms
      of cardiac hypertrophy and failure with high-throughput technology.

PMID- 14679302
TI  - Defining a metabolic phenotype in the brain of a transgenic mouse model of
      spinocerebellar ataxia 3.
AB  - Many of the spinocerebellar ataxias (SCAs) are caused by expansions of CAG
      trinucleotide repeats encoding abnormal stretches of polyglutamine. SCA3 or
      Machado-Joseph disease (MJD) is the commonest dominant inherited ataxia disease,
      with pathological phenotypes apparent with a CAG triplet repeat length of 61-84.
      In this study a mouse model of SCA3 has been examined which was produced using a
      human yeast artificial chromosome containing the MJD gene with a CAG triplet
      expansion of 84 repeats. These mice have previously been shown to possess a mild
      progressive cerebellar deficit. NMR-based metabolomics/metabonomics in
      conjunction with multivariate pattern recognition identified a number of
      metabolic perturbations in SCA3 mice. These changes included a consistent
      increase in glutamine concentration in tissue extracts of the cerebellum and
      cerebrum and spectra obtained from intact tissue using magic angle spinning (1)H
      NMR spectroscopy. Furthermore, these profiles demonstrated metabolic
      abnormalities were present in the cerebrum, a region not previously implicated in
      SCA3. As well as an increase in glutamine both brain regions demonstrated
      decreases in GABA, choline, phosphocholine and lactate (representing the
      summation of lactate in vivo, and postmortem glycolysis of glucose and glycogen).
      The metabolic changes are discussed in terms of the formation of neuronal
      intranuclear inclusions associated with SCA3. This study suggests high-resolution
      (1)H-NMR spectroscopy coupled with pattern recognition may provide a rapid method
      for assessing the phenotype of animal models of human disease.

PMID- 14679303
TI  - Regional variations in ABC transporter expression along the mouse intestinal
      tract.
AB  - The ATP-binding cassette (ABC) family of proteins comprise a group of membrane
      transporters involved in the transport of a wide variety of compounds, such as
      xenobiotics, vitamins, lipids, amino acids, and carbohydrates. Determining their
      regional expression patterns along the intestinal tract will further characterize
      their transport functions in the gut. The mRNA expression levels of murine ABC
      transporters in the duodenum, jejunum, ileum, and colon were examined using the
      Affymetrix MuU74v2 GeneChip set. Eight ABC transporters (Abcb2, Abcb3, Abcb9,
      Abcc3, Abcc6, Abcd1, Abcg5, and Abcg8) displayed significant differential gene
      expression along the intestinal tract, as determined by two statistical models (a
      global error assessment model and a classic ANOVA, both with a P < 0.01).
      Concordance with semiquantitative real-time PCR was high. Analyzing the promoters
      of the differentially expressed ABC transporters did not identify common
      transcriptional motifs between family members or with other genes; however, the
      expression profile for Abcb9 was highly correlated with fibulin-1, and both genes
      share a common complex promoter model involving the NFkappaB, zinc binding
      protein factor (ZBPF), GC-box factors SP1/GC (SP1F), and early growth response
      factor (EGRF) transcription binding motifs. The cellular location of another of
      the differentially expressed ABC transporters, Abcc3, was examined by
      immunohistochemistry. Staining revealed that the protein is consistently
      expressed in the basolateral compartment of enterocytes along the anterior
      posterior axis of the intestine. Furthermore, the intensity of the staining
      pattern is concordant with the expression profile. This agrees with previous
      findings in which the mRNA, protein, and transport function of Abcc3 were
      increased in the rat distal intestine. These data reveal regional differences in
      gene expression profiles along the intestinal tract and demonstrate that a
      complete understanding of intestinal ABC transporter function can only be
      achieved by examining the physiologically distinct regions of the gut.

PMID- 14679304
TI  - Reciprocal regulation of urokinase receptor (CD87)-mediated cell adhesion by
      plasminogen activator inhibitor-1 and protease nexin-1.
AB  - Protease nexin-1 (PN-1) and plasminogen activator inhibitor-1 (PAI-1) are serine
      protease inhibitors that bind to the extracellular matrix protein vitronectin
      (VN) with high affinity. PAI-1 is known to inhibit cell adhesion and migration by
      binding to VN and inhibiting the interaction with integrins or the urokinase
      receptor (uPAR). Unexpectedly, PN-1 was found to increase the association between
      VN and uPAR in the presence of enzymatically active uPA. Through this mechanism
      PN-1 also stimulated uPAR-dependent cell adhesion to immobilized VN. In contrast
      to PAI-1, PN-1 did not influence VN binding to integrins or integrin-mediated
      cell adhesion. Upon adhesion of monocytes to VN there was an accumulation of uPAR
      and PN-1 at the interface between the cell and the matrix, whereas on fibronectin
      (FN) both components were distributed evenly over the whole cell as visualized by
      confocal microscopy. Immunohistochemistry of atherosclerotic vessels indicated
      that PN-1 was found associated with smooth muscle cells, macrophages and
      platelets. In some regions of the diseased vessels PN-1 was in close proximity to
      VN and uPAR, but no PN-1 was present in normal vessels. These results indicate a
      novel function of PN-1 linked to complex formation with uPA that leads to the
      regulation of VN-dependent adhesion of leukocytes.

PMID- 14679305
TI  - Restoration of full-length adenomatous polyposis coli (APC) protein in a colon
      cancer cell line enhances cell adhesion.
AB  - The APC tumour suppressor gene is mutated in most colon cancers. A major role of
      APC is the downregulation of the beta-catenin/T-cell factor (Tcf)/lymphoid
      enhancer factor (LEF) signalling pathway; however, there are also suggestions
      that it plays a role in the organization of the cytoskeleton, and in cell
      adhesion and migration. For the first time, we have achieved stable expression of
      wild-type APC in SW480 colon cancer cells, which normally express a truncated
      form of APC. The ectopically expressed APC is functional, and results in the
      translocation of beta-catenin from the nucleus and cytoplasm to the cell
      periphery, and reduces beta-catenin/Tcf/LEF transcriptional signalling. E
      cadherin is also translocated to the cell membrane, where it forms functional
      adherens junctions. Total cellular levels of E-cadherin are increased in the
      SW480APC cells and the altered charge distribution in the presence of full-length
      APC suggests that APC is involved in post-translational regulation of E-cadherin
      localization. Changes in the location of adherens junction proteins are
      associated with tighter cell-cell adhesion in SW480APC cells, with consequent
      changes in cell morphology, the actin cytoskeleton and cell migration in a wound
      assay. SW480APC cells have a reduced proliferation rate, a reduced ability to
      form colonies in soft agar and do not grow tumours in a xenograft mouse tumour
      model. By regulating the intracellular transport of junctional proteins, we
      propose that APC plays a role in cell adhesion in addition to its known role in
      beta-catenin transcriptional signalling.

PMID- 14679306
TI  - Dispersal of Golgi matrix proteins during mitotic Golgi disassembly.
AB  - During mitosis, the mammalian Golgi disassembles into numerous vesicles and
      larger membrane structures referred to as clusters or remnants. Following
      mitosis, the vesicles and clusters reassemble to form an intact Golgi in each
      daughter cell. One model of Golgi biogenesis states that Golgi matrix proteins
      remain assembled in mitotic clusters and then serve as a template for Golgi
      reassembly. To test this idea, we performed a 3D-computational analysis of
      mitotic cells to determine the extent to which these proteins remain in mitotic
      clusters. As a control we used brefeldin A-induced Golgi disassembly which causes
      dispersal of Golgi enzymes, but leaves matrix proteins in remnant structures.
      Unlike brefeldin A-treated cells, in which matrix proteins were clearly sorted
      from non-matrix proteins, we observed extensive dispersal of matrix proteins in
      metaphase cells with no evidence of differential sorting of these proteins from
      other Golgi proteins. The extensive disassembly of matrix proteins argues against
      their participation in a stable template and supports a self-assembly mode of
      Golgi biogenesis.

PMID- 14679307
TI  - Electrical stimulation directly induces pre-angiogenic responses in vascular
      endothelial cells by signaling through VEGF receptors.
AB  - Controlling angiogenesis is crucial. Growth factors and cytokines are key
      regulators but a full understanding remains elusive. Endogenous electrical
      potential differences exist within and around the vasculature, both in relation
      to blood flow and in situations where active angiogenesis occurs, such as wound
      healing, development and tumor growth. Recent work shows that electrical
      stimulation induces significant angiogenesis in vivo, through enhanced vascular
      endothelial growth factor (VEGF) production by muscle cells. We report that
      applied electric fields (EFs) of small physiological magnitude directly stimulate
      VEGF production by endothelial cells in culture without the presence of any other
      cell type. EFs as low as 75-100 mV mm-1 (1.5-2.0 mV across an endothelial cell)
      directed the reorientation, elongation and migration of endothelial cells in
      culture. These pre-angiogenic responses required VEGF receptor activation and
      were mediated through PI3K-Akt and Rho-ROCK signaling pathways, resulting in
      reorganization of the actin cytoskeleton. This indicates that endogenous EFs
      might play a role in angiogenesis in vivo by stimulating the VEGF receptor
      signaling pathway, to induce key pre-angiogenic responses. In addition, it raises
      the feasibility of using applied EFs to initiate and guide angiogenesis through
      direct effects on endothelial cells.

PMID- 14679308
TI  - Integrin-linked kinase regulates vascular morphogenesis induced by vascular
      endothelial growth factor.
AB  - Integrin-linked kinase (ILK) is one of the signaling moieties that interact with
      the cytoplasmic domains of integrin beta1 and beta3 subunits. Integrin-mediated
      outside-in signals cooperate with vascular endothelial growth factor (VEGF)
      receptor to promote morphological changes, cell proliferation and motility in
      endothelial cells. In this report we demonstrate that VEGF-induced vessel
      morphogenesis of human umbilical vein endothelial cells (HUVEC) was inhibited by
      the transfection of a dominant negative, kinase-deficient ILK (ILK-KD), as well
      as by treatment with the phosphatidylinositol 3-kinase inhibitor LY294002. VEGF
      induced phosphorylation of protein kinase B (PKB/Akt), a regulator of cell
      survival and apoptosis, on serine 473, but not on threonine 308, in an ILK
      dependent manner. Furthermore, transfection of antisense ILK (ILK-AS) blocked the
      survival effect of VEGF in annexin-V binding assays, and a VEGF-mediated decrease
      in caspase activity was reversed by both ILK-KD and ILK-AS as measured by a
      homogeneous caspase-3/7 assay. We also demonstrate that both chemotactic
      migration and cell proliferation of HUVEC induced by VEGF were suppressed by the
      inhibition of ILK. We conclude that ILK plays an important role in vascular
      morphogenesis mediated by VEGF.

PMID- 14679309
TI  - Characterization of B-type cyclins in the smut fungus Ustilago maydis: roles in
      morphogenesis and pathogenicity.
AB  - Pathogenesis, morphogenesis and cell cycle are connected in the fungal pathogen
      Ustilago maydis. Here we report the characterization of the catalytic subunit of
      the cyclin-dependent kinase, encoded by the gene cdk1, and the two B-type cyclins
      present in this organism, encoded by the genes clb1 and clb2. These cyclins are
      not redundant and appears to be essential for cell cycle. The analysis of
      conditional mutants in cyclin genes indicates that Clb1 is required for G1 to S
      and G2 to M transitions, while Clb2 is specifically required for the onset of
      mitosis. Both Clb1 and Clb2 carry functional destruction boxes, and expression of
      derivatives lacking D-boxes arrested cell cycle at a post-replicative stage. High
      levels of Clb1 generated cells with anomalous DNA content that were
      hypersensitive to microtubule-destabilizing drugs. In contrast, high levels of
      Clb2 induce premature entry into mitosis, suggesting that Clb2 is a mitotic
      inducer in U. maydis. In addition, Clb2 affects morphogenesis, and overexpression
      of clb2 induces filamentous growth. Furthermore, we have found that appropriate
      levels of Clb2 cyclin are critical for a successful infection. Mutant strains
      with half a dose of clb2 or high level of clb2 expression are impaired at
      distinct stages in the infection process. These data reinforces the connections
      between cell cycle, morphogenesis and virulence in this smut fungus.

PMID- 14679310
TI  - The role of annexin 2 in osteoblastic mineralization.
AB  - While the basic cellular contributions to bone differentiation and mineralization
      are widely accepted, the regulation of these processes at the intracellular level
      remains inadequately understood. Our laboratory recently identified annexin 2 as
      a protein involved in osteoblastic mineralization. Annexin 2 was overexpressed
      twofold in SaOSLM2 osteoblastic cells as a fusion protein with green fluorescent
      protein. The overexpression of annexin 2 led to an increase in alkaline
      phosphatase activity as well as an increase in mineralization. Our data suggest
      that the increase in alkaline phosphatase activity does not result from increased
      alkaline phosphatase transcript or protein levels; therefore we evaluated
      mechanism of action. We determined that both annexin 2 and alkaline phosphatase
      activity were localized to membrane microdomains called lipid rafts in
      osteoblastic cells. Annexin 2 overexpression resulted in an increase in alkaline
      phosphatase activity that was associated with lipid microdomains in a cholesterol
      dependent manner. Furthermore, disruption of lipid rafts with a cholesterol
      sequestering agent or reduction of annexin 2 expression by specific antisense
      oligonucleotides each resulted in diminished mineralization. Therefore, intact
      lipid rafts containing annexin 2 appear to be important for alkaline phosphatase
      activity and may facilitate the osteoblastic mineralization process.

PMID- 14679311
TI  - Advanced glycation end products in clinical nephrology.
AB  - As a result of oxidative and carbonyl stress, advanced glycation end products
      (AGEs) are involved in the pathogenesis of severe and frequent diseases and their
      fatal vascular/cardiovascular complications, i.e. diabetes mellitus and its
      complications (nephropathy, angiopathy, neuropathy and retinopathy, renal failure
      and uremic and dialysis-associated complications), atherosclerosis and dialysis
      related amyloidosis, neurodegenerative diseases, and rheumatoid arthritis. They
      are formed via non-enzymatic glycation which is specifically enhanced through the
      presence of oxidative and carbonyl stress, and their ability to form
      glycoxidation products in peptide and protein structures finally modulating or
      inducing biological reactivity. Food can be another source of AGEs; however, high
      serum AGEs in hemodialysis patients might reflect nutritional status better.
      Several methods of renal replacement therapy have been studied in connection with
      the AGE removal, but unfortunately the possibilities are still unsatisfactory
      even if high flux dialysis, hemofiltration, or hemodiafiltration give better
      results than conventional low flux dialysis. AGEs are currently being studied in
      the patients on peritoneal dialysis as their precursors can be formed in the
      dialysis fluid. AGEs can cause damage to the peritoneum and so a loss of
      ultrafiltration capacity. Many compounds give promising results in AGE inhibition
      (inhibition of formation of AGEs, inhibition of their action or degradation of
      AGEs), are tested for these properties, and eventually undergo clinical studies
      (e.g. aminoguanidine, OPB-9195, pyridoxamine, antioxidants, N-phenacylthiazolium
      bromide, antihypertensive drugs, angiotensin-converting enzyme inhibitors and
      angiotensin II receptor-1 antagonists).

PMID- 14679312
TI  - Renal medullary infusion of indomethacin and adenosine. Effects on local blood
      flow, tissue ion content and renal excretion.
AB  - Perfusion of the renal medulla and osmotic hypertonicity of its interstitium are
      the two important features of this zone which can influence body fluid
      homeostasis, especially arterial blood pressure. Separate manipulation of the two
      variables is best obtained with the intramedullary infusion of active agents. In
      this study, a set-up combining the possibility of infusion into the medulla with
      measurement of local blood flow (MBF, laser-Doppler flux) and extracellular ion
      concentration (tissue electrical admittance, Y) was used to determine effects of
      intramedullary indomethacin (Indo) and adenosine (Ado) in anaesthetized rats.
      Intramedullary Indo, 1 mg kg(-1 )h(-1), significantly increased tissue Y, by 12
      +/- 3%, and significantly decreased MBF by 20 +/- 3%. There was also an
      unexplained increase of sodium excretion (U(Na)V) by 169 +/- 24% and of urine
      flow (V) by 62 +/- 6% (n = 10, both p < 0.03). Intramedullary Ado, 5 microg kg(
      1) h(-1), did not alter Y, MBF or U(Na)V, whereas V increased 45 +/- 6% and urine
      osmolality decreased 25 +/- 4% (both changes significant). Elevation of medullary
      interstitial Ado to a level that did not alter MBF or U(Na)V induced a moderate
      defect of urine concentration that was not due to a decrease in ionic medullary
      hypertonicity.

PMID- 14679313
TI  - Chloride channel blockade attenuates the effect of angiotensin II on
      tubuloglomerular feedback in WKY but not spontaneously hypertensive rats.
AB  - Recent studies have shown that calcium-dependent chloride channels may play a
      crucial role in the modulation of the vascular effects of angiotensin II (ANG
      II). Thus, alterations in the function of these channels may be responsible for
      the enhanced renal vasoconstrictor and tubuloglomerular feedback (TGF) response
      to ANG II in spontaneously hypertensive rats (SHR). We investigated the effect of
      the calcium-dependent chloride channel blocker IAA-94 on renal hemodynamics and
      TGF responses. The renal interstitium was perfused with control solution, with
      ANG II, and with both ANG II and IAA-94. In Wistar Kyoto rats (WKY), perfusion
      with ANG II significantly increased renal vascular resistance (RVR), but the
      effect was significantly attenuated by perfusion with ANG II/IAA-94. In SHR, ANG
      II caused a significant elevation of RVR that was not altered by the simultaneous
      infusion of IAA-94. Proximal tubular stop flow pressure (P(sf)) was monitored
      during perfusion of peritubular capillaries with control solution, and
      subsequently with IAA-94, ANG II or both ANG II and IAA-94. TGF response
      magnitude of WKY rats was significantly augmented with ANG II, and this effect
      was suppressed by perfusion with ANG II /IAA-94. However, in SHR peritubular
      perfusion with ANG II/IAA-94 did not suppress the TGF response. We conclude that
      chloride channels susceptible to IAA-94 may play a significant role in modulating
      the effects of ANG II on renal hemodynamics, and that this modulation is absent
      in SHR.

PMID- 14679314
TI  - Influence of trans fatty acids on health.
AB  - The contribution of dietary trans fatty acids (TFAs) on the risk of ischemic
      heart disease (IHD) has recently gained further support due to the results from
      large, prospective, population-based studies. Compared to saturated fat, TFAs
      are, gram to gram, associated with a considerably (2.5- to >10-fold) higher risk
      increment for IHD. A negative effect on the human fetus and on newborns and an
      increase in colon cancer risk in adults are possible but, however, still
      equivocal. Recent findings justify further studies concerning the effect of TFAs
      on allergic diseases in children and on the risk of type-2 diabetes in adults.
      The intake of industrially produced TFAs in European countries is decreasing.
      However, determination of the TFA content in various popular food items collected
      in Danish shops showed that it is likely that persons with a frequent intake of,
      e.g., French fries, microwave oven popcorn, chocolate bars, fast food, etc.,
      consume industrially produced TFAs in amounts far exceeding the average intake,
      and are thereby exposed to an unnecessary health risk. The Danish government has
      decided that oils and fats containing more than 2% industrially produced TFAs
      will not be sold in Denmark after the January 1, 2004.

PMID- 14679316
TI  - Effects of caffeine on the saturated and monounsaturated Fatty acids of the
      newborn rat cerebellum.
AB  - Caffeine (1,3,7-trimethylxanthine) is one of the most commonly consumed drugs in
      our daily life, and its use is increasing. However, very little attention has
      been paid to its potential effects on early growth and development. Because of
      the steady increase in breast feeding of infants and because caffeine diffuses
      readily into breast milk, the present study examined if caffeine intake by
      newborn rats during lactation would affect the saturated and monounsaturated
      fatty acids in the growing cerebellum. A total of 10 timed pregnant rats were
      purchased from the breeder. At birth litters were combined, and 8 pups were
      randomly assigned to each dam without regard to the sex of the pups. Dams with
      litters were divided into 2 groups. Dams of group 1 received a 20% protein diet
      as a control, and dams of group 2 received a 20% protein diet plus caffeine (4
      mg/100 g BW). Pups were killed at day 10. The cerebellums were removed, weighed
      and homogenized. Gas chromatograph-mass spectrometry was used to identify and
      quantify free fatty acids. Chronic caffeine exposure from birth to day 10 in pups
      through the maternal milk resulted in a decrease in cerebellum weight, a
      significant increase in the saturated fatty acids, and a tendency toward an
      increase of monounsaturated fatty acids. In addition, there was a slight increase
      of some of the polyunsaturated fatty acids. However, there was no difference in
      food intake of the lactating dams and weight gain of the pups between the groups.
      These data indicate that early caffeine intake by the suckling pups alters the
      composition of fatty acids of the cerebellum; thus, avoidance of caffeine during
      lactation is critical. The risks and benefits of caffeine administration in
      premature infants must be carefully evaluated during this rapid period of brain
      growth.

PMID- 14679315
TI  - Limited lipid-lowering effects of regular consumption of whole soybean foods.
AB  - AIM: To examine cardiovascular health benefits of foods containing a whole
      soybean extract. METHODS: The study design was a randomized, placebo-controlled
      crossover trial of consuming soy-based milk and yoghurt (treatment) or equivalent
      dairy products (control) for 5 weeks each. Twenty-six mildly
      hypercholesterolaemic and/or hypertensive volunteers were recruited from the
      community as study volunteers, of which 23 completed. Main outcome measures
      included clinic and ambulatory blood pressure, arterial compliance, lipids, fatty
      acids and isoflavones in fasted blood and 24-hour urinary isoflavone excretion.
      Nutrient intakes were assessed initially and after each 5-week period. Multiple
      regression analyses were used to determine predictor variables in statistical
      models; order effects were tested by repeated measures ANOVA. Changes in Lp(a)
      were determined by Wilcoxon signed ranks tests; other differences between
      treatment and control were assessed by t tests. RESULTS: Plasma and urinary
      isoflavones were markedly increased by whole soy supplementation but there were
      no overall differences in plasma lipids, blood pressure or arterial compliance
      between the soy and dairy diets. However, in 8 equol-positive subjects (equol
      detected in either plasma or urine), retrospective analysis revealed significant
      reductions in total cholesterol (8.5%), LDL cholesterol (10%), LDL:HDL ratio
      (13.5%), plasma triglycerides (21%) and lipoprotein(a) (11%) with the soy diet.
      These reductions were independent of changes in polyunsaturated fat and other
      macronutrient intakes. CONCLUSIONS: Regular consumption of whole soybean milk and
      yogurt products had no effect on plasma lipids, blood pressure or arterial
      compliance in at-risk subjects, despite substantially increasing isoflavone
      levels in blood and urine. Retrospective analysis suggests that improvement of
      plasma lipids may have been limited to equol-positive subjects.

PMID- 14679317
TI  - Anthony S. Tavill, MD, FACP, FRCP, FACG.

PMID- 14679318
TI  - Helicobacter pylori infection and reflux esophagitis in children with chronic
      asthma.

PMID- 14679319
TI  - Evaluation of unexplained chest pain by the gastroenterologist: a continuing
      dilemma.

PMID- 14679320
TI  - Perspectives of chromo and magnifying endoscopy: how, how much, when, and whom
      should we stain?
AB  - The goal of every routine endoscopy in the gut is the early diagnosis of
      malignant and premalignant changes of the mucosa. Chromo- and magnifying
      endoscopes are exciting new tools and offer detailed analysis of the colonic
      mucosal surface and pit pattern architecture. This review summarizes recent
      advances in endoscopic characterization of colorectal lesions using magnification
      endoscopy and chromoendoscopy. Surface analysis of the colon using
      chromoendoscopy allows a prediction between non-neoplastic and neoplastic lesions
      with high specificity. The precise delineation of the borders and a more detailed
      macroscopic analysis of the lesions are further advantages. In particular, flat
      adenomas and early depressed cancers are now more frequently recognized in
      western countries suggesting that significant lesions were overlooked by
      conventional endoscopy in the past. Furthermore, chromoendoscopy can be used in a
      targeted fashion to screen for sporadic adenomas. Finally, in surveillance
      colonoscopy, patients with long-standing ulcerative colitis have a valuable
      benefit if targeted biopsies are performed to detect intraepithelial neoplasias
      after pan-chromoendoscopy with methylene blue. Although there is a long learning
      curve, chromoendoscopy should thus belong to every endoscopists armamentarium.
      However, detailed knowledge about the technique, dyes, and specific staining
      patterns are mandatory before the yield of screening or surveillance colonoscopy
      can be increased. The new detailed images seen with magnifying chromoendoscopy
      are unequivocally the beginning of a new era where new optical developments will
      allow a unique look on cellular structures.

PMID- 14679321
TI  - Helicobacter pylori infection and reflux esophagitis in children with chronic
      asthma.
AB  - BACKGROUND: Reflux esophagitis is uncommon in countries in which most people are
      colonized by H. pylori infection and is extremely rare in persons with reflux
      esophagitis, although esophagitis is detected in almost 50% of children with
      recurrent lower respiratory tract symptoms. HYPOTHESIS: Failure to acquire H.
      pylori can enhance esophagitis risk in children with chronic asthma. PATIENTS AND
      METHODS: Forty-two pediatric out-patients with chronic asthma (mean age 13.2 +/-
      1.18 years, range 12-15 years, 23 boys and 19 girls) were included in the study.
      They had undergone endoscopy with gastric and esophageal biopsies for upper
      dyspeptic complaints. H. pylori positivity was confirmed by positive Giemsa
      staining. Esophagitis was diagnosed by standard histologic procedure (presence of
      intraepithelial leukocytes or basal cell hyperplasia). RESULTS: H. pylori
      colonization was detected histologically in 22 of 42 patients (52.4%) enrolled in
      the study. Histology demonstrated that in asthmatic children with evidence of H.
      pylori infection esophagitis was a dramatically rare finding than in the patients
      without the infection (P < 0.001). It was an unexpected finding, that lung
      function parameters (FEF50, FEF75) were significantly lower in asthmatics
      infected with H. pylori (P < 0.05). CONCLUSION: The present findings suggest
      inverse association between esophagitis and H. pylori in course of asthma in
      pediatric patients.

PMID- 14679322
TI  - Prevalence of Helicobacter pylori infection in health-care personnel of primary
      care and gastroenterology clinics.
AB  - BACKGROUND & AIMS: Helicobacter pylori (Hp) infection clusters within families,
      is usually acquired early in life, and is strongly associated with lower
      socioeconomic status during childhood. Transmission in adulthood is relatively
      rare, and reports on the prevalence of Hp infection among health personnel,
      especially endoscopists, are controversial. The present prospective study
      evaluated the prevalence of Hp infection in health-care workers in primary-care
      clinics and in gastroenterology units. METHODS: Health care personnel from
      gastrointestinal units (n = 191) and primary care-clinics (n = 98) of the Clalit
      Health Services (CHS) in Israel underwent the carbon 13 breath test (13C-UBT) and
      completed a 21-item demographic and socioeconomic questionnaire. The control
      group consisted of 4633 symptomatic patients with no evidence of previous Hp
      infection. RESULTS: The 13C-UBT was positive in 108 gastrointestinal unit
      personnel (73%) and 70 primary-care workers (71%); both rates were statistically
      higher significantly than the 53% positivity in the controls. Comparison of the
      13C-UBT Hp-positive and Hp-negative health-care personnel yielded a significantly
      higher index of crowded living conditions in the Hp-positive group. In the
      gastrointestinal unit workers, Hp positivity was also associated with several
      years in practice, and in the primary-care workers, with Sephardic (Asian and
      African origin) versus Ashkenazi (Europe and American) origin. Profession
      (physician, nurse, technician, secretary, or maintenance worker), history of
      duodenal ulcer, smoking, marital status, and blood group did not have predictive
      value for Hp colonization. CONCLUSIONS: The prevalence of Hp infection in Israel
      is higher in health-care staff of primary-care clinics and gastrointestinal units
      than in the general population. This may be related to socioeconomic facts and
      professional hazard. Further studies are needed to clarify this issue.

PMID- 14679323
TI  - Evaluation of symptom index in identifying gastroesophageal reflux disease
      related noncardiac chest pain.
AB  - BACKGROUND: Symptom index (SI), which represents the percentage of perceived
      gastroesophageal reflux-related symptoms that correlate with esophageal acid
      reflux events (pH <4), has been suggested as a measure to improve diagnosis of
      gastroesophageal reflux (GER)-related noncardiac chest pain (NCCP). Because no
      study has evaluated the value of the symptom index in NCCP patients, data to
      support this claim have yet to be elucidated. AIM: To evaluate the value of SI in
      identifying gastroesophageal reflux disease (GERD)-related NCCP patients.
      METHODS: Patients enrolled in this study were referred by a cardiologist after a
      comprehensive work-up excluded a cardiac cause for their chest pain. All patients
      underwent upper endoscopy to determine esophageal inflammation and 24-hour
      esophageal pH monitoring to assess esophageal acid exposure. Patients were
      instructed to record all chest pain episodes during the pH test. Patients with a
      positive SI (> or =50%) underwent the proton pump inhibitors (PPI) test, which is
      a therapeutic trial using a short course of high dose PPI. RESULTS: A total of 94
      patients with NCCP were included in this study. Forty-seven (50%) had either a
      positive upper endoscopy or an abnormal pH test and were considered GERD
      Positive. Forty-seven patients (50%) had both tests negative and were considered
      GERD-Negative. Total number of reflux episodes and percent total, supine and
      upright time pH less than 4, were significantly higher in the GERD-Positive group
      as compared with the GERD-Negative group (P < 0.0001, P < 0.0001, P = 0.0045, and
      P < 0.0001 respectively). Only 9 (19.1%) patients in the GERD-Positive group and
      5 (10.6%) patients in the GERD-Negative group had a positive SI (p = ns). Eight
      (89%) out of the 9 patients who had a positive SI in the GERD-Positive group and
      2 (40%) out of 5 patients in the GERD-Negative group responded to the PPI test.
      CONCLUSION: Positive SI is relatively uncommon in NCCP patients, regardless if
      GERD is present or absent. Hence, symptom index provides very little improvement
      in diagnosing GERD-related NCCP.

PMID- 14679324
TI  - Are 10 wet swallows an appropriate sample of esophageal motility? Yes and no.
AB  - BACKGROUND: Traditionally 10 wet swallows are used to assess esophageal motility.
      Given this relative small number of swallows concerns have been raised whether
      the abnormal findings based on 10 wet swallows would persist with another set of
      10 wet swallows. PURPOSE: To evaluate whether 10 wet swallows during esophageal
      manometry is an adequate sampling of esophageal motility. METHODS: Over a 4-month
      period 100 consecutive patients (excluding patients with achalasia) were given 20
      liquid (5 ml each) swallows. The standard manometry technique in our laboratory
      was performed using 10 wet swallows with pressure transducers placed 4 cm and 9
      cm above the lower esophageal sphincter (LES). The diagnosis was based on the
      initial 10 swallows. The additional 10 swallows were blinded and separately
      analyzed, then compared with the initial swallows for each patient. RESULTS: Of
      the 100 studies (64 women; mean age 51; range 21-85), 91 had a consistent
      diagnosis for both pairs of 10 swallows. The number of abnormal swallows
      (ineffective or simultaneous) differed between the 2 sets of 10 swallows in 9
      patients, but, when the first 10 were analyzed vs. all 20 swallows only 2
      patients had discordant diagnoses. There was an excellent agreement between the
      1st and 2nd set of 10 swallows (kappa = 0.846) and between the first 10 and all
      20 swallows (kappa = 0.965). CONCLUSIONS: Ten wet swallows are sufficient for
      making a manometric diagnosis, because additional swallows are likely to change
      the diagnosis in only 2% of patients.

PMID- 14679325
TI  - Patient anxiety and elective gastrointestinal endoscopy.
AB  - BACKGROUND: Esophagogastroduodenoscopy (EGD) and colonoscopy (CS) are commonly
      performed procedures that can cause anxiety related to potential findings,
      embarrassment and concern over discomfort. The objective of this study is to
      evaluate patient anxiety associated with diagnostic, sedated outpatient endoscopy
      and to correlate endoscopists' estimations of patient anxiety with those of the
      patient. METHODS: Consecutive patients referred for diagnostic upper endoscopy or
      colonoscopy were evaluated. Anxiety was rated at baseline and immediately before
      the procedure using the State-Trait Anxiety Index (STAI-Y). Patients were
      categorized as whether they had been previously seen by a gastroenterologist in
      the clinic or were referred directly by another physician for endoscopy. Patients
      were also asked to rate their knowledge of the procedure using a visual analog
      scale. Physicians rated patient anxiety and procedure difficulty using 100 mm
      visual analog scales. Sedation administered during each procedure was recorded.
      RESULTS: Ninety-four patients were enrolled; 47 had been referred from the
      gastroenterology clinic and 47 had been directly referred from primary care
      physicians. Thirty-nine percent completed baseline and pre-procedure STAI-Y.
      Endoscopy was associated with a significant increase in state anxiety (baseline,
      31.2 +/- 1.8; procedure, 39.8 +/- 2.2; P = 0.001) but not trait anxiety
      (baseline, 35.4 +/- 1.7; procedure, 36.2 +/- 1.6; P = 0.59). Procedural state
      anxiety was not influenced by age, sex, referral source, type of procedure or
      perceived procedural knowledge but was correlated with trait anxiety (r = 0.38; P
      = 0.02). Physician estimates of patient anxiety did not correlate with either
      procedural state anxiety (r = -0.15; P = 0.37) or the change in state anxiety
      from baseline to the procedure (r = -0.04; P = 0.82). CONCLUSIONS: Diagnostic
      outpatient endoscopy is associated with modest increases in state anxiety that
      are not significantly influenced by age, sex, procedure type, indication, or
      referral source. Endoscopists' ability to estimate patient anxiety is poor but
      this may reflect the generally mild increases in state anxiety that were
      encountered.

PMID- 14679326
TI  - Magnesium hydroxide in ibuprofen tablet reduces the gastric mucosal tolerability
      of ibuprofen.
AB  - GOAL: The study was designed to compare the gastrointestinal tolerability of a
      magnesium hydroxide-containing ibuprofen tablet (buffered ibuprofen) and the
      conventional ibuprofen tablet in healthy volunteers. BACKGROUND: Magnesium
      hydroxide has been shown to increase the rate of absorption of ibuprofen.
      METHODS: A double blind, randomized, 2-period crossover study design was used.
      Twenty healthy men ingested 800 mg ibuprofen 3 times daily either in conventional
      tablets (2 doses of 400 mg) or in tablets containing magnesium hydroxide (2 doses
      of 400 mg ibuprofen and 200 mg magnesium hydroxide). On the 5th day only the
      morning dose was administered. Endoscopy was performed at baseline and on the 5th
      day in both treatments 2 hours after the last dose, and gastric pH was
      determined. In addition, plasma concentrations of ibuprofen were determined up to
      90 minutes. RESULTS: The magnesium hydroxide-containing formulation increased the
      number of subjects evincing erosions in gastric corpus and antrum. In the gastric
      corpus 2 and 7 volunteers had erosions after conventional and buffered ibuprofen,
      respectively (P = 0.08). In the gastric antrum 5 and 13 volunteers showed
      erosions after conventional and buffered ibuprofen, respectively (P = 0.02).
      There was a trend toward faster absorption of ibuprofen when given together with
      magnesium hydroxide. The difference was not however statistically significant.
      CONCLUSIONS: Prolonged use of magnesium hydroxide together with high doses of
      ibuprofen should be avoided, because the combination may incur a higher risk of
      gastrointestinal irritation.

PMID- 14679327
TI  - Ulcerative colitis associated enteritis: is ulcerative colitis always confined to
      the colon?
AB  - Ulcerative colitis (UC) is a chronic inflammatory disease of the colon whose
      etiology is unknown. Small bowel involvement in UC is extraordinarily rare, and
      should make the clinician question the diagnosis. However, we present a case of a
      38-year-old man with voluminous diarrhea following colectomy for well-documented
      UC; he was found to have ulcerative enteritis with histologic features identical
      to UC. Also, for the first time, we present an inclusive review of another 11
      cases of UC associated enteritis (UCAE) reported in the literature, and discuss
      the significance of the entity. We conclude that UC is rarely accompanied by
      enteritis that is distinct from Crohn disease, frequently presents shortly after
      colectomy, and usually is responsive to traditional therapies for inflammatory
      bowel disease (IBD).

PMID- 14679328
TI  - Hepatic hydrothorax: pathophysiology, diagnosis, and management.
AB  - Hepatic hydrothorax occurs in approximately 5 to 12% of patients with cirrhosis
      and portal hypertension. Various therapeutic modalities ranging from dietary and
      pharmacologic interventions to surgical approaches are available for the
      management of this condition. Treatment must be individualized based on the
      patient's response to conservative management as well as the severity of the
      underlying liver disease. Hepatic hydrothorax may be complicated by spontaneous
      bacterial empyema, which portends a poor prognosis with a mortality rate of up to
      20%. All patients with hepatic hydrothorax should be evaluated for possible liver
      transplantation.

PMID- 14679329
TI  - Endoscopic stenting for biliary and pancreatic malignancies.
AB  - Endoscopic treatment of pancreatobiliary malignancies has been recognized in the
      last decades as the treatment of choice in inoperable patients. Endoscopic
      armamentarium includes biliary stents (plastic and metallic) to bypass neoplastic
      strictures of the biliary tree, and pancreatic stents to palliate the obstructive
      pain caused by stenoses of the main pancreatic duct. A major issue is the long
      term patency of plastic stents that will eventually clog on average after 3 to 4
      months. Self-expandable metallic stents have longer patency, but they can also
      become occluded by tumor ingrowth or overgrowth; they are also much more
      expensive; their use is thus recommended in patients with longer life expectancy.
      Decompression of the dilated main pancreatic duct in pancreatic carcinoma may be
      effective in the relief of obstructive pain. Endoscopic palliation in pancreatic
      and biliary malignancies appears safe and effective; management of patient in
      referral centers, with an available team of gastroenterologists with endoscopic
      skills, surgeons, and radiologists is recommended.

PMID- 14679330
TI  - Infection with hepatitis C virus genotype 4 in the United States.
AB  - BACKGROUND: Hepatitis C virus genotype differences seem to be of considerable
      clinical significance because they affect responses to antiviral therapy. HCV
      genotype 4 is rare in the United States and there are few published data
      regarding response to therapy in patients with HCV genotype 4 infection.
      OBJECTIVES: To assess epidemiologic factors associated with HCV genotype 4
      infection in United States and to describe the response rate to therapy with the
      combination of alpha interferon and ribavirin. METHODS: All hepatologists in our
      Division were asked for information about patients they had treated with HCV
      genotype 4. In addition, we searched the computer database from Saint Louis
      University Hospital in the last 40 months (1999 to 2002). Twenty HCV genotype 4
      patients were identified. A retrospective chart review was performed to collect
      information about their demographics, risk factors for acquisition of infection,
      baseline laboratory studies and response to antiviral therapy. RESULTS: A risk
      factor for exposure to HCV was noted in 14 cases (70%); 12 patients had a history
      of illicit drug use, whereas a history of blood transfusion was detected in three
      cases; 1 patient had both risk factors. Only 4 of 20 individuals had fibrosis
      stage 3 or 4 on liver biopsy. Seventeen patients were treated, 14 of whom
      completed therapy; 10 patients were sustained responders. CONCLUSIONS: As with
      other HCV genotypes, most patients with HCV genotype 4 in the United States
      acquire the infection through intravenous drug use, liver disease is often mild
      to moderate in severity and 59% of our patients had a sustained virologic
      response after combination therapy with interferon and ribavirin.

PMID- 14679331
TI  - Autonomic dysfunction and gastroparesis in cirrhosis.
AB  - BACKGROUND: Patients with cirrhosis of the liver frequently present with many
      gastrointestinal complaints that are most likely due to abnormal gastrointestinal
      motility. The cause of these motility disorders in cirrhotics is unknown,
      however, underlying autonomic dysfunction may play a role. OBJECTIVE: To
      determine the association between autonomic dysfunction and delayed gastric
      emptying in cirrhotic patients. METHODS: We prospectively studied 20 patients
      with cirrhosis of the liver and postprandial abdominal pain, nausea, and vomiting
      and 10 asymptomatic patients with Hepatitis C (HCV) and no evidence of cirrhosis.
      All patients underwent 5 standardized cardiovascular tests to assess autonomic
      function. Each test was scored on a continuum from 0 (normal) to 5 (severe
      disease), thus producing a composite score of 0 to 5 for each subject. A
      composite score of greater than 1.5 was considered abnormal, with 5 representing
      severe autonomic involvement. A solid phase gastric emptying study was performed
      in each patient and a gastric retention of greater than 50% at 100 minutes was
      considered abnormal. RESULTS: The mean percent retention at 100 minutes was 70.7%
      in the cirrhotic group vs. 26.1% (P < 0.001) in the patients with HCV and no
      evidence of cirrhosis (controls). The composite autonomic score for the cirrhotic
      group was 3.4 vs. 1.2 (P < 0.001) in the controls. CONCLUSIONS: Our results
      suggest that gastroparesis is common in patients with cirrhosis of the liver, and
      may account for gastrointestinal symptoms of postprandial abdominal pain, nausea,
      and vomiting. The presence of autonomic dysfunction correlates positively with
      underlying motility disorders, such as delayed gastric emptying.

PMID- 14679332
TI  - Efficacy of the Za self-expandable metal stent for palliation of malignant
      biliary obstruction.
AB  - BACKGROUND: The efficacy and safety of the uncoated self-expandable Za metal
      stent for palliation of malignant distal biliary obstruction was prospectively
      analyzed. METHODS: Twenty-one patients with unresectable malignant tumors
      involving mid to distal common bile duct who presented with obstructive jaundice
      underwent endoscopic implantation of an uncoated self-expandable metal stent.
      Technical success with stent placement, adverse events, patient survival,
      duration of stent patency, and device performance were analyzed. RESULTS:
      Endoscopic biliary stenting was successful in all patients. No adverse events
      were encountered. The mean follow-up period of the 21 patients was 128 days
      (range, 3-263): 14 died of progressive disease at mean of 81 days (range, 3-210),
      3 remain alive (at days 239, 250, and 263), and 4 were lost to follow-up (at days
      90, 91, 92, and 116). The mean duration of stent patency was 249 days. Tumor
      ingrowth was observed in one patient (5%). Minor technical problems were
      encountered in 3 patients: 1 proximal deployment, 1 distal deployment, and
      difficulty associated with the delivery system in 1. CONCLUSIONS: The Za-metal
      stent provided effective palliation for patients with inoperable malignant
      biliary tumors. Although minor technical problems were encountered with stent
      deployment, the overall stent patency, efficacy, and safety profile appear
      satisfactory.

PMID- 14679333
TI  - How often are liver function tests normal in acute biliary pancreatitis?
AB  - BACKGROUND: The biochemical markers of a biliary etiology of acute pancreatitis
      (AP) include an ALT elevation of more than 3 times the upper range of normal
      (ULN) and a serum total bilirubin greater than 3 mg%. OBJECTIVES: To analyze the
      frequency of normal LFTs (Bilirubin, ALP, ALT, and AST) in patients with biliary
      AP. DESIGN: In this prospective study data collected for other ongoing studies on
      AP in the division of Gastroenterology in the last 20 years were analyzed.
      MATERIAL AND METHODS: Serum total Bilirubin, AST, ALT, and ALP levels in 269
      patients with biliary AP out of 728 cases of AP of various etiologies were
      analyzed. The biliary etiology was confirmed on the basis of gallstones
      documented by transabdominal US or at surgery. RESULTS: We noted normal
      bilirubin, AST, ALT, and ALP levels in 14.5%, 12.3%, 11.2%, and 26.4% of cases of
      acute biliary pancreatitis respectively. When all the 4 laboratory tests were
      considered collectively, the incidence of normal values was 10.4%. We also noted
      an ALT elevation of <3 x ULN in 16.7% of cases of biliary AP and 43.5% of cases
      had a T. Bilirubin level of less than 3 mg %. CONCLUSIONS: Almost 15 to 20% of
      patients with biliary AP manifest with normal LFTs. The clinician should not
      exclude a biliary etiology solely on the basis of normal LFTs.

PMID- 14679334
TI  - Ticlopidine induced acute cholestatic hepatitis complicated with pure red cell
      aplasia.

PMID- 14679335
TI  - Possible autoimmune thrombocytopenia associated with pegylated interferon-alpha2a
      plus ribavarin treatment for hepatitis C.

PMID- 14679336
TI  - Tension pneumoperitoneum as a late complication of surgical gastrostomy.

PMID- 14679337
TI  - Carcinoma of the colon presenting as Streptococcus salivarius sepsis.

PMID- 14679338
TI  - Severe atrophic gastritis with extreme hypergastrinemia and gene expression of
      ornithine decarboxylase (ODC) and cyclo-oxygenase-2 (COX-2) expression:
      comparison with gastric cancer.

PMID- 14679339
TI  - Clinical differentiation between secondary and spontaneous bacterial peritonitis.

PMID- 14679340
TI  - Hepatocellular carcinoma associated with extramammary Paget disease.

PMID- 14679341
TI  - Anti-HCV seroprevalence in chronic HCV patients' children in Turkey.

PMID- 14679342
TI  - [Editorial "meta-analysis"].

PMID- 14679343
TI  - [Clinical significance of the Krogh-Poulsen bite test in mandibular dysfunction].
AB  - INTRODUCTION: The bite test was initially described as the Krogh-Poulsen test
      consists of biting a flat and thin wedge placed unilaterally between the molars.
      Temporomandibular joint (TMJ) pain located on the ipsilateral side is considered
      as muscular, when on the contralateral side pain signifies a joint problem.
      Although this test is widely used, no scientific evaluation of its real clinical
      value has been published. MATERIAL AND METHOD: A prospective study is conducted
      in 32 patients exhibiting temporomandibular pain (n=40) at the bite test. The
      results of the bite test were compared with results of computed tomography of the
      TMJ. Several criteria are studied: joint space narrowing, retrusion of the
      mandibular condyle in occlusal position, bony signs of joint degeneration. Chi
      square and Student's t test were used for statistical analysis of correlations
      between clinical findings and radiological abnormalities. RESULTS: Significant
      results demonstrated a high degree of radiologically detectable disorders in
      patients with joint pain as defined by the bite test. All of these patients
      presented at least one radiological sign of joint disease. There was also a low
      degree of radiologically detected joint disturbance in patients with muscular
      pain according to the bite test, 70% of them presenting no radiological
      abnormality. DISCUSSION: It is concluded that the bite test is of significant
      value for evaluation of TMJ disorders and can be useful for the indication of
      complementary radiological examinations.

PMID- 14679344
TI  - [Maxillofacial trauma by defenestration: 64 cases].
AB  - OBJECTIVE: There has been little work reported in the literature concerning
      trauma resulting from high level falls and almost none devoted to maxillofacial
      trauma following defenestration. The purpose of this work was to report the first
      series of defenestration victims who incurred maxillofacial trauma. METHOD: This
      retrospective series included all patients treated at the Pitie-Salpetriere
      hospital between July 1994 and July 1999, all units included: surgery intensive
      care, neurosurgical emergency, orthopedic surgery or maxillofacial surgery.
      RESULTS: Female gender predominated in comparison with studies concerning high
      level falls (SR=0.5) with no difference concerning age (mu=31.5, sigma2=9.1).
      Fifty percent of the patients had a maxillofacial involvement. Death ensued in
      17.2% (11/64 patients). The height of the fall among survivors ranged from one
      floor to eight floors; third-floor falls accounted for 31%. Defenestration was
      intentional in 70.3% of the cases, accidental in 17.1% and undetermined in 12.6%.
      The suicide attempts involved 13 patients with maniac depressive psychosis, 11
      with depression, 6 with schizophrenia, 2 with undetermined familial problems, and
      12 with no specific history. Four patients were drug abusers and 3 were
      alcoholics. Fifty percent of the victims were living in precarious social and
      economical conditions. The maxillofacial injuries included: 20 mandibular
      fractures, 15 Lefort fractures (I, II, III or combined), 2 blow out fractures, 7
      fractures of the orbital roof, 15 fractures of the malar bone, 7 fractures of the
      nose bones, and 11 fractures of the naso-ethmoido-maxillo-fronto-orbital complex.
      On the average, patients lost 6 dental elements. The mean Glasgow index was 7.9.
      Extrafacial injuries included limb fractures (89%), chest trauma (73.4%), brain
      lesions (67%), spinal injury (40.6%), and abdominal injury (26.5%). CONCLUSION:
      The psychic and social vulnerability of the defenestration patient aggravated by
      the trauma is a fundamental dimension which must be taken into consideration
      during the initial management of these patients.

PMID- 14679345
TI  - [Primary intraosseous carcinoma of the jaws: results of treatment of 9 cases and
      proposed classification].
AB  - INTRODUCTION: Primary intraosseous carcinoma of the jaws is a rare squamous cell
      carcinoma arising in the jaw, having no initial connection with the oral mucosa
      and presumably developing from residues of the odontogenic epithelium.
      OBJECTIVES: To present 9 cases and to propose a staging system of primary
      intraosseous carcinoma of the jaws. CASES AND METHODS: Careful assessment of the
      clinical, radiological and histological examination of the specimens identified 9
      patients with primary intraosseous carcinoma of the jaws. RESULTS: The
      male/female ratio was 8/1 and the mean age of patients at the time of diagnosis
      was 61.7 years. All lesions were located in the mandible. Usually, clinical
      symptoms had benign aspect and delay the diagnosis. Radiographic features were
      unilocular osteolytic lesion and ill-defined margins were usually noted with a
      mean tumor size of 3.4 centimeters. The mean delay of the diagnosis was 4.9
      months. Surgery at the tumor site consisted of hemi-mandibulectomy in all cases.
      All patients but one had neck dissection. The postoperative radiotherapy mean
      dose was 62.6 Gy. Histologically, most squamous cell carcinomas were well
      differentiated with keratinization. All lymph nodes metastasis had capsular
      involved. Complications occurred in 2 cases. Four patients had recurrences in the
      mean delay of 13.8 months. The estimated overall 2-and 5-years survival was 65%
      and 46.5% respectively. DISCUSSION: Primary intra-osseous carcinoma of the jaws
      is a rare tumor none classified by UICC with poor prognosis. We recommend an
      aggressive treatment with postoperative radiotherapy. We propose a computer
      tomographic classification: T1 (tumor strictly intra-osseous), T2 (tumor with
      cortical destruction without involvement of adjacent soft-tissues) and T3 (tumor
      involvement of adjacent soft-tissues).

PMID- 14679346
TI  - [The Temporal Smile. Speech therapy for facial palsy patients after temporal
      lengthening myoplasty].
AB  - We present our approach to speech therapy developed for patients with definitive
      peripheral facial palsy treated by temporal lengthening myoplasty. The main goal
      is to rehabilitate smiling function, a major component in social communication
      codes, by transferring labial and jugal functions to the transferred temporal
      muscle. Several phases are involved. The first phase, termed the Mandibular Smile
      involves mobilization of the mandible (original function of the temporal) by
      contraction of the transferred temporal and inducing an elevation of the
      commissura labiorum. The second phase, the Voluntary Temporal Smile is obtained
      by contraction of the temporal independently of mandibular movement which remains
      under voluntary control. The smile produces should become as symmetrical as
      possible. Finally, the last phase is designed to achieve a spontaneous smile
      independent of mandibular movement Spontaneous Temporal Smile. Temporal
      contraction should produce both a "real" expressive smile and good quality
      articulate speech, saliva evacuation, prehension, and labial junction.
      Acquisition of the Temporal Smile involves cerebral plasticity implying
      rehabilitation processes both on the peripheral and central levels.

PMID- 14679347
TI  - [Reconstruction of the nasal pyramid after extended transfixing loss of lateral
      tissue].

PMID- 14679349
TI  - [Cellular hemangioma of the parotid gland associated with an infection by
      cytomegalovirus].
AB  - We report a case in a two and a half month old boy presenting a mass in the right
      parotid gland. Sonography showed a vascular tumor. Magnetic resonance imaging
      showed an expansive process of the parotid gland measuring 61 x 39 mm taking the
      contrast with hypo signal in T1 and hyper signal in T2-weighted images. The
      parotid was extirpated with preservation of the facial nerve. Microscopically the
      diagnosis of cellular hemangioma associated with CMV infection was made.
      Hemangiomas of the parotid gland is frequent; the most common tumor in children;
      the association of juvenile hemangioma of the parotid gland and cytomegalovirus
      (CMV) is extremely rare: a single case was reported in the literature. The
      pathologic significance of this association is still discussed, although several
      experimental studies suggested a relationship between the infection by the
      cytomegalovirus and this tumor. Our objective is to describe the anatomo-clinical
      aspects of this lesion and to elucidate the pathologic significance of this
      association.

PMID- 14679348
TI  - [Brain abscess and diffuse cervico-facial cellulitis: complication after
      mandibular third molar extraction].
AB  - The authors report a case of cervico-facial cellulitis with brain abscess after
      mandibular third molar removal. This is the observation of a 26 years old boy
      surgically treated for a cervico-facial cellulitis ten days after a third molar's
      removal. He was given anti-inflammatory drugs after removal for analgesia. After
      a phase of clinical improving, the patient developed pulmonary and brain abscess
      with neurological signs. He needed neurosurgery in emergency. After eight weeks
      of antibiotic treatment, the patient was cured with aftereffects (jaw
      constriction and sensory disorders of the right thigh). Cerebro-meningeal
      complications of diffuse cervico-facial cellulitis are exceptional but are
      responsible for heavy aftereffects. This observation confirms that using anti
      inflammatory drugs for analgesia is associated with a higher rate of
      complications after dental removal.

PMID- 14679350
TI  - [Aphthae and aphthosis].

PMID- 14679351
TI  - [Advanced oral lesions. Pemphigus vulgaris].

PMID- 14679352
TI  - Tadalafil (cialis) for erectile dysfunction.

PMID- 14679353
TI  - Choice of an antipsychotic.

PMID- 14679358
TI  - Antiphospholipid syndrome.
AB  - Antiphospholipid syndrome has received considerable attention from the medical
      community because of its association with a number of serious clinical disorders,
      including arterial and venous thromboembolism, acute ischemic encephalopathy,
      recurrent pregnancy loss, thrombocytopenia, and livido reticularis. It can occur
      within the context of several diseases, mainly autoimmune disorders, and is then
      called secondary antiphospholipid syndrome. However, it may be also be present
      without any recognizable disease, or so-called primary antiphospholipid syndrome.
      There is no defined racial predominance for primary antiphospholipid syndrome,
      although a higher prevalence of systemic lupus erythematosus (SLE) occurs in
      African Americans and the Hispanic population. Multiple terms exist for this
      syndrome, some of which can be confusing. Lupus anticoagulant syndrome, for
      example, is a misleading term, because patients may not necessarily have SLE, and
      it is associated with thrombotic rather than hemorrhagic complications. To avoid
      further confusion, antiphospholipid syndrome is currently the preferred term for
      this clinical syndrome. Antiphospholipid antibodies are found in 1% to 5% of
      young healthy control subjects; however, the incidence increases with age and
      coexistent chronic disease. The syndrome occurs most commonly in young to middle
      aged adults; however, it also can occur in children and the elderly. Among
      patients with SLE, the prevalence of antiphospholipid antibodies is high, ranging
      from 12% to 30% for anticardiolipin antibodies, and 15% to 34% for lupus
      anticoagulant antibodies. In general, anticardiolipin antibodies occur
      approximately five times more often then lupus anticoagulant in patients with
      antiphospholipid syndrome. This syndrome is the most common cause of acquired
      thrombophilia, associated with either venous or arterial thrombosis or both. It
      is characterized by the presence of antiphospholipid antibodies, recurrent
      arterial and venous thrombosis, and spontaneous abortion. Rarely, patients with
      antiphospholipid syndrome may have fulminate multiple organ failure, or
      catastrophic antiphospholipid syndrome. This is caused by widespread microthrombi
      in multiple vascular beds, and can be devastating. Patients with catastrophic
      antiphospholipid syndrome may have massive venous thromboembolism, along with
      respiratory failure, stroke, abnormal liver enzyme concentrations, renal
      impairment, adrenal insufficiency, and areas of cutaneous infarction. According
      to the international consensus statement, at least one clinical criterion
      (vascular thrombosis, pregnancy complications) and one laboratory criterion
      (lupus anticoagulant, antipcardiolipin antibodies) should be present for a
      diagnosis of antiphospholipid syndrome. The hallmark result from laboratory tests
      that defines antiphospholipid syndrome is the presence of antibodies or
      abnormalities in phospholipid-dependent tests of coagulation, such as dilute
      Russell viper venom time. There is no consensus for treatment among physicians.
      Overall, there is general agreement that patients with recurrent thrombotic
      episodes require life-long anticoagulation therapy and that those with recurrent
      spontaneous abortion require anticoagulation therapy and low- dose aspirin
      therapy during most of gestation. Prophylactic anticoagulation therapy is not
      justified in patients with high titer anticardiolipin antibodies with no history
      of thrombosis. However, if a history of recurrent deep vein thrombosis or
      pulmonary embolism is established, long-term anticoagulant therapy with
      international normalized ratio (INR) of approximately 3 is needed.

PMID- 14679360
TI  - Food-drug interaction: grapefruit juice augments drug bioavailability--mechanism,
      extent and relevance.
AB  - More than a decade has passed since it was unintentionally discovered that
      grapefruit juice interacts with certain drugs. The coadministration of these
      drugs with grapefruit juice can markedly elevate drug bioavailability, and can
      alter pharmacokinetic and pharmacodynamic parameters of the drug. The predominant
      mechanism for this interaction is the inhibition of cytochrome P-450 3A4 in the
      small intestine, resulting in a significant reduction of drug presystemic
      metabolism. An additional mechanism is, presumably, the inhibition of P
      glycoprotein, a transporter that carries drug from the enterocyte back to the gut
      lumen, resulting in a further increase in the fraction of drug absorbed. Some
      calcium channel antagonists, benzodiazepines, HMG-CoA reductase inhibitors and
      cyclosporine are the most affected drugs. A single exposure to one glass of the
      juice can usually produce the maximal magnitude of the interaction. The data
      available so far, concerning this interaction and its clinical implications, are
      reviewed in this article. It is likely that more information regarding this
      interaction will accumulate in the future, and awareness of such is necessary for
      achieving optimal drug therapy.

PMID- 14679361
TI  - Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate
      reductase polymorphism and serum B vitamins on homocysteine levels in pregnant
      women.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of the
      interaction between the C677T mutation in the 5,10-methylenetetrahydrofolate
      reductase (MTHFR) genotypes and serum levels of B vitamins on serum homocysteine
      levels in pregnant women. DESIGN: A cross-sectional study. SETTING: Ewha Womans
      University Hospital, Seoul, Korea. SUBJECTS: A total of 177 normal pregnant
      women, 24.6+/-1.1 weeks of gestation, in a 6-month period during 2001-2002.
      INTERVENTIONS: Serum vitamin B2, vitamin B6, and homocysteine analyses were
      conducted using high-performance liquid chromatography methods. Serum folate and
      vitamin B12 concentrations were determined using a radioimmunoassay kit. MTHFR
      gene mutation was investigated by the polymerase chain reaction of a genomic DNA
      fragment. RESULTS: Serum homocysteine was higher in women with the T/T genotype
      than those with the C/T or C/C genotype of the MTHFR gene (P<0.05). Serum
      homocysteine was negatively correlated with serum folate in all MTHFR genotypes
      (P<0.001), and the correlation between the two serum levels was the strongest in
      the T/T genotype. Serum homocysteine was higher in the subjects with the T/T
      MTHFR genotype only when the serum folate was below the median level. Explanatory
      power of B vitamin status as predictors of serum homocysteine levels was more
      pronounced in the T/T genotypes (68.5%) compared with the C/T (37.9%) or C/C
      genotypes (20.6%). CONCLUSIONS: Serum homocysteine levels in pregnant women
      varied significantly with MTHFR genotype and the serum B vitamin status. Higher
      serum folate, vitamin B2, and vitamin B12 concentrations may lessen the MTHFR
      genotypic effect on serum homocysteine levels.

PMID- 14679362
TI  - Validity and reproducibility of the food frequency questionnaire used in the
      Shanghai Women's Health Study.
AB  - To evaluate the validity and reliability of the food frequency questionnaire
      (FFQ) used in the Shanghai Women's Health Study (SWHS), 200 SWHS participants
      were recruited for a dietary calibration study. Study participants completed an
      FFQ at baseline and 24-h dietary recalls (24-HDR) twice per month consecutively
      for 12 months. At the end of the study, a second FFQ was administered. Of the 200
      study participants, 196 completed 24 or more days of 24-h dietary recalls, 191
      completed two FFQs from whom the results of this report were based. The FFQ
      included the foods that accounted for 86% of the foods recorded in the 24-HDR
      surveys. Validity of the FFQ was evaluated by comparing intake levels of major
      nutrients and foods obtained from the second FFQ with those derived from the
      multiple 24-HDR. The median intake for major nutrients, rice, poultry and meat
      derived from the second FFQ and the 24-HDR was similar, with the differences
      ranging from 1.3 to 12.1%. The FFQ tended to overestimate the intake level of
      total vegetables and total fruits, and the differences were explained mainly by
      over-reporting seasonal vegetables and fruits consumption in the FFQ. Nutrient
      and food intake assessed by the FFQ and the multiple 24-HDR correlated very well,
      with the correlation coefficients being 0.59-0.66 for macronutrients, 0.41-0.59
      for micronutrients, and 0.41-0.66 for major food groups. The reliability of the
      FFQ was assessed by comparing the correlation and median intake of nutrients and
      food groups obtained from the two FFQs that were administered approximately 2 y
      apart. The median intake levels for selected nutrients and food groups derived
      from the two FFQs were similar with differences below 10%. At the individual
      level, the intake levels of these dietary variables obtained from two FFQs also
      correlated well. When nutrient and food group intakes were categorized into
      quartiles, FFQ and 24-HDR produced exact agreement rates between 33 and 50%.
      Misclassification to adjacent quartile was common, ranging from 34-48%, while
      misclassification to an extreme quartile was rare (1-6%). These data indicate
      that the SWHS FFQ can reliably and accurately measure usual intake of major
      nutrients and food groups among women in Shanghai.

PMID- 14679363
TI  - Dietary intake of n-3, n-6 fatty acids and fish: relationship with hostility in
      young adults--the CARDIA study.
AB  - BACKGROUND: Hostility has been shown to predict both the development and
      manifestation of coronary disease. Examining the inter-relation of dietary intake
      of fish and of polyunsaturated (n-3 and n-6) essential fatty acids with hostility
      may provide additional insights into the cardioprotective effect of dietary fish
      and polyunsaturated fatty acids. OBJECTIVE: To examine the association of dietary
      n-3, n-6 fatty acids and fish with level of hostility in a sample of 3581 urban
      white and black young adults. DESIGN: Cross-sectional observational study as part
      of an ongoing cohort study. A dietary assessment in 1992-1993 and measurement of
      hostility and other covariates in 1990-1991 were used in the analysis. RESULTS:
      The multivariate odds ratios of scoring in the upper quartile of hostility
      (adjusting for age, sex, race, field center, educational attainment, marital
      status, body mass index, smoking, alcohol consumption and physical activity)
      associated with one standard deviation increase in docosahexaenoic acid (DHA,
      22:6) intake was 0.90 (95% CI=0.82-0.98; P=0.02). Consumption of any fish rich in
      n-3 fatty acids, compared to no consumption, was also independently associated
      with lower odds of high hostility (OR=0.82; 95% CI=0.69-0.97; P=0.02).
      CONCLUSIONS: These results suggest that high dietary intake of DHA and
      consumption of fish rich in n-3 fatty acids may be related to lower likelihood of
      high hostility in young adulthood. The association between dietary n-3 fatty
      acids and hostile personality merits further research.

PMID- 14679364
TI  - Adequate intake values for dietary fibre based on faecal bulking indexes of 66
      foods.
AB  - OBJECTIVE: To determine an adequate daily intake value for dietary fibre (AIdf)
      based on faecal bulking indexes (FBIs) for 66 foods of known total dietary fibre
      (TDF) content. DESIGN: FBIs of 66 foods were measured and expressed as wheat bran
      equivalents (WBEfb) per 100 g of food. A daily WBEfb requirement for humans was
      calculated from faecal bulk generated per gram of wheat bran TDF in humans, using
      a critical faecal mass of 200 g/day for protection against large bowel disease.
      TDF content was regressed against WBEfb content for all 66 foods assayed, and an
      AIdf value obtained by substituting the calculated human WBEfb requirement into
      the regression equation. METHOD: FBI was measured using a validated rat assay,
      with eight large (400+/-50 g) rats per group, preadapted to dietary fibre, and
      fed adequate restricted diets containing test foods at inclusion rates consistent
      with human intakes. The critical faecal mass was based on epidemiological
      studies, and the faecal bulk generated per gram of wheat bran TDF was the mean of
      27 published values. RESULTS: WBEfb requirements for humans were calculated to be
      90 g/day, corresponding to a faecal output of 200 g/day. The regression equation
      relating WBEfb measured in the FBI assay to TDF in all 66 foods was
      TDF=0.491WBEfb + 3.19, R2=0.81 Substituting the human WBEfb requirement of 90 g
      into the regression equation gave an AIdf value of 40.9 g TDF/day. CONCLUSION:
      The AIdf value of 40.9 g TDF/day based on faecal bulking supports the AIdf of 38
      g TDF/day recently set by the Institute of Medicine (USA), for young men, based
      on protection against heart disease. The AIdf value is obtained from the relation
      between the effects of foods and their content of mixed function, plant cell wall
      dietary fibres within the food matrices, and should not be used to guide intakes
      of extrinsic functional polysaccharides.

PMID- 14679365
TI  - Daily moderate amounts of red wine or alcohol have no effect on the immune system
      of healthy men.
AB  - OBJECTIVE: To investigate whether the daily intake of red wine (RW) at a dose
      which inversely correlates with cardiovascular disease (CVD) risk modulates
      immune functions in healthy men. DESIGN: Randomized single-blind trial with four
      intervention periods. SETTING: The Institute of Nutritional Physiology, Federal
      Research Centre for Nutrition, Karlsruhe, Germany. SUBJECTS: A total of 24
      healthy males with moderate alcohol consumption patterns were recruited and all
      completed the study. INTERVENTION: Participants consumed 500 ml of RW (12%
      ethanol (ETOH)) or 500 ml of a 12% ETOH dilution per day for a period of 2 weeks.
      To control the potential effects of RW polyphenols, accordingly 500 ml/day of
      dealcoholized red wine (DRW) and of red grape juice (RGJ) were given. The
      following immune parameters were measured before beverage consumption and at 1
      and 2 weeks following beverage consumption: phagocytic activity of neutrophils
      and monocytes, production of tumor necrosis factor-alpha (TNFalpha), interleukin
      2 and -4, transforming growth factor-beta, TNFalpha mRNA, lymphocyte
      proliferation, lytic activity of natural killer cells, and percentage of
      apoptotic lymphocytes. RESULTS: Consumption of a moderate volume of alcohol with
      RW and with a 12% ETOH dilution had no effect on immune functions in healthy
      males. Consumption of polyphenol-rich beverages (DRW and RGJ) did not affect
      immunity-related parameters. CONCLUSIONS: Daily moderate consumption of alcohol
      and of RW for 2 weeks at doses which inversely correlate with CVD risk has no
      adverse effects on human immune cell functions. Polyphenol-rich beverages such as
      RGJ and DRW further do not suppress immune responses in healthy men.

PMID- 14679366
TI  - Evaluation of foot-to-foot bioelectrical impedance analysis for the prediction of
      total body water in oncology outpatients receiving radiotherapy.
AB  - OBJECTIVE: To investigate the accuracy of total body water (TBW) predicted by
      foot-to-foot bioelectrical impedance compared with a deuterium oxide dilution
      technique in oncology outpatients receiving radiotherapy. DESIGN: Cross-sectional
      design. SETTING: Two private Australian radiation oncology facilities. SUBJECTS:
      In all, 27 subjects (23 males; four females); mean age 62 (+/-15) y; mean BMI
      26.2 kg/m2 (+/- 3.6). INTERVENTION: TBW was measured using a deuterium oxide
      dilution technique and predicted using foot-to-foot bioelectrical impedance
      (Tanita Inc., Tokyo, Japan, Models TBF 410 and 300GS). RESULTS: The mean (s.d.)
      values for predicted and measured TBW was 41.5 (6.7) and 39.7 (8.7) l,
      respectively, indicating a mean bias to overestimation by the foot-to-foot
      impedance of 1.8 l. However, a significant negative correlation between the mean
      of the measurements of TBW and their difference (r=-0.40; P=0.04) indicates a
      progressive underestimation of TBW by foot-to-foot impedance as the water content
      of the body increases. The analysis of 95% limits of agreement (+/-2 s.d.) showed
      that for most individuals the TBW predicted by foot-to-foot impedance can vary as
      much as 12 l above or 8.6 l below the actual TBW measured by a deuterium oxide
      dilution technique. CONCLUSION: There is good agreement between foot-to-foot
      bioelectrical impedance with a gold standard technique at the group level.
      However, the significant correlation between the difference of predicted and
      measured TBW, and the wide limits of agreement between the two methods, indicates
      that the use of foot-to-foot impedance in assessing TBW may lead to unacceptable
      error in individuals.

PMID- 14679367
TI  - Effects of a combined micronutrient supplementation on maternal biological status
      and newborn anthropometrics measurements: a randomized double-blind, placebo
      controlled trial in apparently healthy pregnant women.
AB  - OBJECTIVE: To investigate the possible beneficial effects of a micronutrient
      supplementation to apparently healthy pregnant women on maternal biological
      status and new born anthropometric characteristics. SETTING: Departments of
      Obstetric of the University Hospital of Grenoble (France) and Lyon (France),
      Laboratoire of Biology of Oxidative Stress, UFR de Pharmacie. Grenoble (France).
      STUDY DESIGN: Double-blind, randomized placebo-controlled intervention trial.
      SUBJECTS: A total of 100 apparently healthy pregnant women were recruited at 14+/
      2 weeks of gestation to delivery. At the end, they were 65 women to follow out
      the study. INTERVENTIONS: Daily consumption over gestation of a micronutrients
      supplement or placebo. MAIN OUTCOME MEASURES: Plasma micronutrient levels and
      oxidative stress parameters were measured in mothers at 14 and 38 weeks of
      gestation. New born's anthropometric characteristics were measured at delivery.
      RESULTS: In the supplemented group, folic acid, vitamin C, E, B2, B6 and beta
      carotene levels were higher than in the placebo group. Oxidative stress
      parameters were not different between the groups. Birth weights were increased by
      10% and the number of low newborn weights (<2700 g) decreased significantly when
      the mother received the supplementation. Maternal plasma Zn levels were
      positively correlated to the newborn heights. CONCLUSION: A regular intake of a
      micronutrient supplement at nutritional dose may be sufficient to improve
      micronutrient status of apparently healthy pregnant women and could prevent low
      birth weight of newborn.

PMID- 14679368
TI  - Influence of the recall period on self-reported alcohol intake.
AB  - OBJECTIVE: To estimate the accuracy of recall on self-reported alcohol intake.
      DESIGN: Population-based random sample. SETTING: The Danish Health and Morbidity
      Survey 1994. SUBJECTS: The study is based on 6,354 persons chosen at random among
      the adult Danish citizens. The response rate was 77%. MAIN OUTCOME MEASURE:
      Number of alcoholic drinks consumed on each day during the last week. RESULTS:
      For self-reported alcohol intake on the last Saturday, respondents with a recall
      period of one day have the shortest recall period (reference group) and
      respondents with a recall period of seven days the longest. Respondents with a
      recall period of seven days reported significant lower alcohol intake (Odds
      Ratio: 0.56). The reported alcohol intake declines when the recall period
      increases. The decline in recall of alcohol intake is very clear already after 2
      3 days. CONCLUSION: The systematic decrease in reported alcohol use with
      increased recall period indicates problems in correctly reporting alcohol intake
      for a full week. Many surveys use recall periods that are longer than a week and,
      therefore, underreported alcohol intake is expected to be even higher.

PMID- 14679369
TI  - Characteristics of the Mini-Nutritional Assessment in elderly home-care patients.
AB  - OBJECTIVE: To assess the risk of malnutrition among elderly people living at home
      and receiving regular home-care services using the Mini-Nutritional Assessment
      (MNA) and to study the characteristics of the instrument in this patient group.
      DESIGN: A cross-sectional study using the MNA score to assess the nutritional
      status of elderly home-care patients. SETTING: Municipal home-care services in
      rural Finland. SUBJECTS: A total of 178 (65%) out of 272 eligible patients aged
      75-94 y agreed to participate. MAJOR OUTCOME METHODS: MNA questionnaire,
      anthropometrics, structured questionnaire, menu record. RESULTS: According to
      MNA, 3% were malnourished (MNA < 17 points), 48% at risk for malnutrition (17
      23.5 points) and 49% well nourished (>23.5 points). The mean MNA score was 23.4.
      Weight loss, psychological stress, nutritional status, decline in food intake,
      self-perceived health status and mid-arm circumference (MAC) showed the strongest
      significant correlations (P=0.0001) to total MNA score. MNA questions with the
      strongest significant intercorrelations (P=0.0001) were body mass index with MAC
      and calf circumference; and the decline of food intake and self-perceived
      nutritional status. The number of eating problems correlated significantly to the
      MNA score (P=0.0011). Those with chewing and swallowing problems (n=64, 36%) had
      a significantly lower MNA score than others (P=0.0001). Dry mouth together with
      chewing and swallowing problems (n=40, 22%) reduced the MNA score even further
      (P=0.0001). CONCLUSIONS: The results suggest that MNA is a useful tool in the
      identification of elderly home-care patients at risk for malnutrition.

PMID- 14679370
TI  - Iron deficiency and risk factors for lower iron stores in 6-24-month-old New
      Zealanders.
AB  - OBJECTIVES: To determine the prevalence of biochemical iron deficiency and
      identify factors associated with ferritin levels among 6-24-month-old urban South
      Island New Zealand children. DESIGN: Cross-sectional survey conducted from May
      1998 to March 1999. SETTING: The cities of Christchurch, Dunedin and
      Invercargill. SUBJECTS: A total of 323 randomly selected 6-24-month-old children
      participated (response rate 61%) of which 263 provided a blood sample. METHODS: A
      complete blood cell count, zinc protoporphyrin, serum ferritin and C-reactive
      protein were measured on nonfasting venipuncture blood samples, 3-day weighed
      food records and general questionnaire data were collected. RESULTS: Among
      children with C-reactive protein<10 mg/l (n=231), 4.3% had iron deficiency
      anaemia, 5.6% had iron deficiency without anaemia, and 18.6% had depleted iron
      stores, when a ferritin cutoff of < or =12 g/l was used. Age (negative), sex
      (girls>boys), ethnicity (Caucasian>non-Caucasian), weight-for-age percentiles
      (negative) and birth weight (positive) were associated with ferritin after
      adjusting for infection and socioeconomic status. When current consumption of
      iron fortified formula and >500 ml of cows' milk per day were included, these
      were associated with a 22% increase and 25% decrease in ferritin, respectively
      (R2=0.28). CONCLUSIONS: The presence of suboptimal iron status (29%) among young
      New Zealand children is cause for concern, even though severe iron deficiency is
      rare, because children with marginal iron status are at risk of developing severe
      iron deficiency if exposed to a physiological challenge.

PMID- 14679371
TI  - Effects of early extra fluid and food intake on breast milk consumption and
      infant nutritional status at 5 months of age in an urban and a rural area of
      Burkina Faso.
AB  - OBJECTIVE: To assess the effects of early extra fluid and food intake on breast
      milk consumption and the effects of food intake on 5-month-old infant nutritional
      status. DESIGN: Cross-sectional surveys. Infants were selected by random choice.
      SETTINGS: Urban and rural Burkina Faso. SUBJECTS: A total of 97 urban and 69
      rural infants were recruited, but 67 and 51, respectively, completed the surveys.
      Infant selection criteria were: age (5 +/- 0.5-month old), thriving, breastfed,
      having Burkinabe parents in study area for a year, study conditions accepted by
      parents. INTERVENTION: Surveys were conducted respectively in January and
      February 2001 (urban), and 2002 (rural) during the cool season. They were
      performed by home visit. With the help of health workers and traditional
      midwives, families were informed of the studies' objectives and gave agreement.
      Food intakes were estimated by test-weighing for breast milk and precise weighing
      techniques for other foods. Socioeconomic status of households, anthropometry of
      infants and mothers were also recorded. Breast milk samples were collected from
      each mother's breast and analysed for lipid and fatty acid concentrations.
      RESULTS: Daily breast milk intake did not differ between urban (776 +/- 262 g)
      and rural areas (835 +/- 265 g). Porridge intake was, respectively, 128 +/- 105
      and 96 +/- 49 g. Median extra fluid intake was, respectively, 79 and 122 g. In
      both areas, porridge and fluid intake had no effect on breast milk consumption.
      In urban areas, infant nutritional status at 5 months was better than at birth.
      CONCLUSION: Breast milk intake and nutritional status of predominantly breastfed
      infants at 5 months of age, living in both urban and rural settings, were not
      affected by the consumption of extra fluid or food intake.

PMID- 14679372
TI  - A comparison of lutein and zeaxanthin concentrations in formula and human milk
      samples from Northern Ireland mothers.
AB  - BACKGROUND: Two carotenoids, lutein and zeaxanthin are found in the retinal
      pigment epithelium of the eye where they are believed to protect it against
      oxidative and light damage. The amounts of these carotenoids consumed by
      premature infants are not known. OBJECTIVE: The objective of the investigation
      was to measure these carotenoids in human and formulae milks. DESIGN: In all, 28
      human milk samples were obtained at various times between days 1 and 41 of
      lactation from 13 mothers. Six formula milks commonly used in hospitals were also
      analysed. SETTING: Mothers who provided the milk samples had infants in the
      neonatal ward at the Royal Maternity Hospital, Belfast. RESULTS: Median lutein
      and zeaxanthin concentrations in human milk were 4.79 (range 0.42-9.98) nmol/g
      fat and 0.55 (0.00-1.70) nmol/g fat, respectively. Five of the six formula milks
      also contained lutein and zeaxanthin with concentrations that varied over a wide
      range (0.7-9.7 and 0.1-1.2 nmol/g fat, respectively). CONCLUSIONS: Carotenoid
      concentrations usually decreased with the duration of lactation. Some formula
      milks that were specially formulated for premature infants contained high
      concentrations of the lutein and zeaxanthin and the source may be egg yolk.
      SPONSORSHIP: These studies were supported by the University of Ulster and the
      Northern Ireland Mother and Baby Appeal.

PMID- 14679373
TI  - Serum selenium and cancer mortality: a nested case-control study within an age-
      and sex-stratified sample of the Belgian adult population.
AB  - OBJECTIVE: To study the predictive power of serum selenium with regard to cancer
      mortality in a large sample of the Belgian population given the lack of coherence
      in the results of observational epidemiological studies in this domain. DESIGN: A
      prospective case-control study within a stratified sample of the Belgian male and
      female population. SUBJECTS: A total of 201 cases randomly selected from all
      cancer deaths (N=343) during a 10-y mortality follow-up of a large age- and sex
      stratified sample of the total Belgian population aged 25-74 y were matched for
      age and gender with 603 controls. STATISTICS: Conditional logistic regression for
      both univariate and multivariate analyses using tertile distribution of serum
      selenium in controls. Odds ratios (ORs) are adjusted for 10 baseline
      characteristics. RESULTS: Unadjusted ORs of cancer deaths taking the highest
      tertile of serum selenium as a reference: in male subjects T1/T3 is 2.2 (CI 1.3
      3.7) (P for trend 0.011), whereas in female subjects a nonsignificant OR of 0.8
      is observed. In multivariate analyses, no significant modifications of the ORs
      are observed for the predictive relation of serum selenium with cancer mortality.
      Besides serum selenium, beta-carotene intake and smoking are independent
      predictors in male subjects. CONCLUSIONS: In this nested case-control study of a
      stratified sample from the Belgian population, serum selenium is an independent
      predictor of cancer mortality in male subjects only, in a country with rather
      high serum selenium levels with respect to most other European countries.

PMID- 14679374
TI  - Plasma taurine and cysteine levels following an oral methionine load:
      relationship with coronary heart disease.
AB  - OBJECTIVE: To test the hypothesis that endogenous synthesis of taurine from
      methionine is impaired in people with coronary heart disease (CHD). DESIGN:
      Nested case-control. SUBJECTS: Indian Asian and white European males aged 35-60
      y. Both racial group included patients with CHD and healthy controls. Samples
      from 20 subjects in each of the four groups were selected at random.
      INTERVENTION: Fasting blood samples were taken before and 6 h after consumption
      of methionine (100 mg/kg body weight) MEASUREMENTS: Plasma concentrations of
      taurine, cysteine, pyridoxal-5-phosphate and 4-pyridoxic acid. RESULTS: Fasting
      plasma taurine values were higher in Indian Asian cases than controls, but not
      significantly different between European cases and controls. Postload taurine
      values were higher in cases than controls in both racial groups (P=0.002).
      Fasting plasma cysteine was higher in cases than controls (P=0.002) and higher in
      Indian Asians than Europeans (0.007), but there were no significant differences
      between any of the groups in postload cysteine values, nor in plasma pyridoxal-5
      phosphate or 4-pyridoxic acid. CONCLUSIONS: Taurine production from methionine
      was not impaired in patients with CHD, but fasting plasma cysteine was higher in
      CHD cases than controls.

PMID- 14679375
TI  - Increased body weight and improved quality of life in AIDS patients following V-1
      Immunitor administration.
AB  - OBJECTIVES: Development of affordable and safe therapy to reverse the loss of
      body mass is of critical importance since AIDS-related wasting is associated with
      increased mortality. METHOD: We have demonstrated earlier that oral therapeutic
      HIV vaccine, V-1 Immunitor (V1), tested in a small group of AIDS patients in
      Thailand not only increases T-cell counts and decreases the viral load but also
      results in weight gain and prolonged survival. To further expand this
      observation, we retrospectively analyzed 650 HIV-positive patients who were
      followed for an average of 23 weeks. RESULTS: The treatment with V1 resulted in a
      sustained and statistically significant increase in body mass across the whole
      population (mean+/-s.e.; 1.5+/-0.4 kg; P=6.5E-015). Among them, 384 (59%)
      patients gained an average of 4.2+/-0.2 kg; 107 (17%) had unchanged weight; and
      159 (24%) had lost 3.8+/-0.3 kg. Thus, the prevailing majority of patients (76%)
      were able to gain or maintain weight. Treatment was well tolerated; in a survey
      of health status in a comparable but separate group of 382 patients, about 85%
      reported subjective improvement after V1 treatment, 6% reported no difference,
      and 9% of the patients reported minor adverse reactions, which did not last more
      than 1 week. Subjective improvement coincides with the reduction or clearance of
      oral thrush or mucocutaneous candidiasis in 87.5% of the patients. CONCLUSIONS:
      In an open label setting, V1 increases body weight, subjective assessment of
      quality of life, and is safe and effective for HIV patients with weight loss.
      These data provide the impetus of using V-1 Immunitor as an affordable and easy
      to-administer means of treating AIDS-associated wasting and opportunistic
      infections.

PMID- 14679376
TI  - CO2 production during acute infection in malnourished Malawian children.
AB  - OBJECTIVE: This study tested the hypotheses that the rate of CO2 production is
      less in marasmic children with acute infection when compared to well-nourished
      children, but greater when compared to uninfected marasmic children. DESIGN: A
      descriptive comparison of children aged 12-60 months who had their rates of CO2
      production measured using a stable isotope tracer dilution method while receiving
      feedings. Body mass index (BMI) was the best measure of lean body mass available
      in this study. SETTING: Queen Elizabeth Central Hospital, Blantyre, Malawi.
      SUBJECTS: A total of 56 children were studied, 28 with marasmus and acute
      infection, 16 with marasmus, and 12 well nourished with acute infection. Those
      with acute infection had malaria, pneumonia, or sepsis. RESULTS: Well-nourished
      children with acute infection produced more CO2 than marasmic children (344+/-60
      vs 225+/-65 mmol CO2/h, mean+/-s.d., P<0.001; 24.2+/-4.6 vs 18.4+/-5.4 mmol
      CO2/BMI h, P=0.001). However, the rate of CO2 production in marasmic children
      with acute infection was not greater than in uninfected marasmic children (225+/
      65 vs 228+/-61 mmol CO2/h). The observed rate of CO2 production was greater than
      that which could be produced from the dietary intake alone (29.6 vs. 25.8 mmol
      CO2/kg h). CONCLUSIONS: Marasmic children do not increase energy expenditure in
      response to acute infection, as well-nourished children do. Dietary energy
      provided to marasmic children should be at least 420 kJ/kg day.

PMID- 14679377
TI  - A prospective randomised trial to determine the efficacy of a low glycaemic index
      diet given in addition to healthy eating and weight loss advice in patients with
      coronary heart disease.
AB  - OBJECTIVE: Recent epidemiological and prospective trial evidence suggests that
      consumption of a low glycaemic index (LGI) diet will reduce coronary risk. We
      hypothesise that introduction of an LGI diet will improve the metabolic profile
      of patients who have undergone coronary artery bypass grafting. DESIGN: We
      conducted a randomised parallel group trial comparing a control group (n=29, age
      61.8+/-9 y), who received currently advocated healthy eating dietary advice only,
      to an intervention group, who received healthy eating advice emphasising LGI
      carbohydrates (n=26, age 63.6+/-9.4 y) over a 12-week period in free-living
      patients with coronary heart disease. Outcome measures included fasting glucose,
      insulin, total cholesterol, high-density lipoprotein cholesterol, very low
      density lipoprotein cholesterol, low density lipoprotein cholesterol and
      triglycerides. RESULTS: A significant lower dietary glycaemic index was achieved
      in the group assigned to an LGI diet compared to the healthy eating control group
      (71+/-1 vs 81+/-1); fibre intake was also higher in the LGI group (20+/-1 vs 15+/
      1 g). All biochemical markers of glucose and lipid metabolism measured were
      similar after 12 weeks of the LGI diet or control diet. DISCUSSION: The LGI group
      achieved a significant LGI and a higher dietary fibre intake. However, there was
      no measurable significant effect of either the LGI diet or the health eating diet
      on lipid levels; this may have been hidden by concurrent drug therapy.

PMID- 14679378
TI  - Predictors for cod-liver oil supplement use--the Norwegian Women and Cancer
      Study.
AB  - OBJECTIVE: To assess the use of cod-liver oil supplements among Norwegian women
      and to examine dietary, lifestyle, demographic, and health factors associated
      with use of this supplement. DESIGN: Cross-sectional study. SETTING AND SUBJECTS:
      The study is based on data from a food frequency questionnaire from 1998 answered
      by 37,226 women aged 41-55 y, who in 1991/1992 participated in the Norwegian
      component of the European Prospective Investigation into Cancer and Nutrition
      (EPIC). The Norwegian EPIC cohort was based on a random nation-wide sample of
      Norwegian women. RESULTS: Cod-liver oil supplement use was reported by 44.7% of
      the participating women. Subjects with higher education, high physical activity
      level, and body mass index (BMI) in the normal range were more likely to use cod
      liver oil supplements. Consumption did also increase with increased age as well
      as with increased reported consumption of fruits, vegetables, fatty fish, lean
      fish, and vitamin D (excluding the vitamin D contribution from cod-liver oil).
      Energy intake was higher among cod-liver oil users than nonusers. Whole-year
      daily users of cod-liver oil were also more likely to take other dietary
      supplements (OR=2.45, 95% CI: 2.28-2.62). Never smokers were more likely to use
      cod-liver oil supplements than current smokers. CONCLUSION: Use of cod-liver oil
      is associated with several sociodemographic factors, self-reported health issues,
      and intake of fish, fruit, and vegetables. When assessing the relationship
      between cod-liver oil use and occurrence of chronic diseases potential
      confounders need to be considered. Cod-liver oil use seemed not to be matched
      with vitamin D needs. Thus, emphasis on assessing vitamin D status by measuring
      levels in blood should be investigated further, in particular, among people
      living in northern latitudes.

PMID- 14679379
TI  - Dietary attitudes and changes as well as use of supplements and complementary
      therapies by Australian and Finnish women following the diagnosis of breast
      cancer.
AB  - OBJECTIVE: This study investigated self-reported dietary attitudes and changes,
      and use of complementary approaches among breast cancer patients in relation to
      age, education and time since diagnosis. DESIGN AND SETTING: Australian (ABC,
      N=215) and Finnish (FBC, N=139) breast cancer patients were surveyed at the
      university cancer centres with voluntary participation. Logistic regression
      models were used to adjust for differences in demographic patient characteristics
      between the groups. The influence of demographic variables was further studied
      separately or combined. RESULTS: In all, 30% of FBC patients and 39% of ABC
      patients reported having changed their diet (P=0.033). Higher education, younger
      age and longer time from diagnosis were significantly associated with the
      probability of changes. The main changes reported included reduced consumption of
      animal fat, sugar and red meat, and increased consumption of fruits and
      vegetables. In all, 6% of ABC and 4% of FBC patients had stopped smoking and 24%
      of ABC and 27% of FBC patients reported to have increased their level of physical
      exercise. Choices were associated with age (P<0.007), length of the disease
      history (P <0.01) and level of education (P <0.002). CONCLUSION: One-third of
      breast cancer patients surveyed reported to have changed their dietary habits.
      Both populations reported a need for dietary and lifestyle counselling. This need
      was experienced as poorly recognised by the physicians at present, and warrants
      future studies in dietary behaviour of breast cancer patients.

PMID- 14679380
TI  - Patterns of food consumption in Vietnam: effects on socioeconomic groups during
      an era of economic growth.
AB  - OBJECTIVE: To identify if the nutritional status and improvements in Vietnam
      during the 1990s applied equally to the key vulnerable population groups (poor,
      rural, and ethnic minority) as it did to the nonpoor-largely in the urban areas.
      DESIGN: This study used cross-sectional analyses in the context of inequalities
      occurring in the diets of the poor and nonpoor that accompanied economic
      improvements during the Vietnam Doi Moi period. SETTING: During the Doi Moi
      period in Vietnam. SUBJECTS: A cross-sectional analysis was conducted on data
      using 23,839 individuals (4800 households) from the Vietnam Living Standard
      Survey (VLSS) in 1992-1993 and 28,509 individuals (6,002 households) from the
      Vietnam Living Standard Survey in 1997-1998. Analysis for changes in food
      consumption was conducted on 17,763 individuals (4,305 households) that were
      included in both surveys. INTERVENTION: None. RESULTS: After initiation of Doi
      Moi in 1986, the average Vietnamese person reached the dietary adequacy of 2,100
      kcal per day per capita in the early 1990s, but this did not improve during the
      next decade. The structure of diet shifted to less starchy staples while proteins
      and lipids (meat, fish, other protein-rich higher fat foods) increased
      significantly. Although the gap in nutrient intake between the poor and the
      nonpoor decreased, the proportion of calories from protein- and lipid-rich food
      for the poor is lower than for the nonpoor. The VLSS data showed that the
      increase of protein and lipid foods in total energy structure over the 5 y
      between the VLSS studies for poor households was 0.43% (CI=0.33, 0.53) and 0.47%
      (CI=0.41, 0.54) lower, respectively, than for nonpoor households (P<0.0001).
      Inequalities compared to the nonpoor were also found in both quantity and quality
      of food consumption. For example, poor households consumed (quantity) 127
      kcal/day (CI=119, 135) less from meat, and 32 kcal/day (CI=27, 38) less from fats
      than nonpoor households (P<0.0001), and the proportion of calories consumed
      (quality) by poor households was 5.8% (CI=5.4, 6.1) less from meat and 0.96%
      (CI=1.2, 0.7) less from fats than by nonpoor households (P<0.0001). CONCLUSIONS:
      Although the key vulnerable groups-rural, poor, and minority populations-showed
      improvements in diet, there still remains an inequity between these groups and
      the nonpoor of the population. In particular, the vulnerable groups consumed less
      of their daily consumption from the desirable high-quality proteins of animal
      foods and fats, and more from cereals and other starches-lagging the better-off
      populations in desired composition.

PMID- 14679381
TI  - Influence of repeated consumption of beverages containing sucrose or intense
      sweeteners on food intake.
AB  - OBJECTIVE: To investigate the influence of ingestion of beverages with sucrose or
      with intense sweeteners on food intake (FI) and on hunger ratings in before and
      after a month of daily consumption of beverages. DESIGN: Experimental study.
      SETTING: Department of Physiology, University Hospital, Dijon, France. SUBJECTS:
      In all, 12 men and 12 women, aged 20-25 y. INTERVENTION: Four beverages contained
      either sucrose (E+:100 g/l, 1672 kJ) or intense sweeteners (E-: null energy
      content) and were flavoured with either orange (O) or raspberry (R). FI was
      measured in the lab during two 2-consecutive-day periods, carried out on 2
      successive weeks (session 1). The subjects drank 2 l of either E+ or E- beverages
      on the first day of both weekly periods, according to a balanced randomised
      design. E+ was paired with O for 50% of subjects and with R for the other 50%.
      Subjects were then habituated over a 4-week period to both beverages, consuming 1
      l of E+ beverage on odd days and 1 l of E- drink on even days. After this period,
      the measurements of session 1 were repeated (session 2, weeks 7-8). Finally, FI
      was measured for two more 2-day periods (weeks 9-10) after the association
      between flavour and energy content was reversed (session 3). RESULTS: The E-
      drinks were less palatable than the E+ drinks. Besides, we observed that FI was
      not reduced in response to a liquid extra caloric load and there was no change in
      hunger ratings after the beverages in any of the sessions. CONCLUSION: Ingestion
      of caloric beverages induced a positive energy balance and the continuous
      exposure phase to these beverages over 1 month did not improve FI adaptation in
      response to the extra energy provided by the beverages.

PMID- 14679382
TI  - Impact of nutrition counselling on nutrition knowledge and nutrient intake of 7-
      to 9-y-old children in an atherosclerosis prevention project.
AB  - OBJECTIVE: To assess the impact of nutrition counselling given to 7.5- to 9-y-old
      children and their parents on children's nutrition knowledge and nutrient
      intakes. DESIGN AND SUBJECTS: The study children are participants in a
      prospective, randomised STRIP study (Special Turku Coronary Risk Factor
      Intervention Project for Children), whose aim was to decrease the intakes of
      saturated fat and cholesterol while increasing the intake of unsaturated fat in
      the intervention children from the age of 7 months onwards. Nutrition counselling
      was given only to the parents until the child's age of 7 y. Nutrition knowledge
      and nutrient intakes (total energy, total fat, saturated fat, unsaturated fat and
      sodium) were studied in a time-restricted cohort of 47, 7-y-old intervention and
      51 control children. Thereafter, nutrition counselling was given both to the
      children and parents. Children's nutrition knowledge and nutrient intakes were
      measured again at the age of 9 y. RESULTS: Biannual nutrition counselling given
      to the intervention children and the parents maintained the differences in
      saturated fatty acid intake attained during the intervention given to the parents
      alone (11.5 vs 13.3 E% (percent of energy intake), at the age of 7 y, P<0.01;
      11.1 vs 13.4 E% at the age of 9 y, respectively; P<0.01). The intervention
      children used more polyunsaturated fatty acids at the age of 9 y than the control
      children (5.7 vs 5.1 E%, P=0.05). At 7 y, the intervention and control children
      had similar nutrition knowledge scores (total knowledge score 12.9 vs 12.0,
      respectively, P=0.13). After 1.5 y of nutrition intervention, at 9 y, the
      intervention children's nutrition knowledge was higher than that of the controls
      (total nutrition score 16.5 vs 13.2, respectively, P<0.001) and the ability to
      explain the reasons for their picture choices in the nutrition knowledge test had
      increased. CONCLUSION: This study showed that only a relatively short period of
      counselling with low input is needed to increase in children's nutrition
      knowledge and ability to explain nutrition-related subjects if advice has first
      been given to the parents and if the parents have received reinforcement and
      concrete help with parent-child communication after their children have been
      involved in the counselling. The differences attained in nutrient intake could
      also be maintained.

PMID- 14679383
TI  - Effect of red clover-derived isoflavone supplementation on insulin-like growth
      factor, lipid and antioxidant status in healthy female volunteers: a pilot study.
AB  - BACKGROUND: Isoflavones are estrogen-like plant compounds that may protect
      against cardiovascular disease and endocrine-responsive cancer. Isoflavones may,
      because of their ability to act as selective estrogen receptor modulators, alter
      insulin-like growth factor (IGF) status. OBJECTIVE: The aim of this study was to
      assess the effect of 1-month isoflavone supplementation (86 mg/day red clover
      derived isoflavones) on IGF status. DESIGN AND SUBJECTS: Healthy pre- (n=16) and
      postmenopausal (n=7) women were invited to take part in a randomised, placebo
      controlled crossover study with a minimum 2-month washout period. RESULTS: : For
      premenopausal subjects, the change in IGF-1, IGF-BP1 and IGF-BP3 assessed at
      different points of the menstrual cycle did not differ between isoflavone and
      placebo phase. However, the change in IGF-1, when examined pre- and post
      supplementation, was nonsignificantly reduced (P=0.06) on the isoflavone
      supplement compared to placebo. For postmenopausal subjects, the change in IGF-1,
      IGF-BP1 and IGFBP-3 concentrations over the supplementation period did not differ
      between isoflavone or placebo phase. Isoflavones increased HDL in postmenopausal
      women compared to placebo (P=0.02) but did not alter either cholesterol or
      triacylglycerol concentrations, and had no effect on antioxidant status.
      CONCLUSIONS: This study shows that 1-month supplementation with red clover
      isoflavones has a positive effect on HDL cholesterol, but at most a small effect
      on IGF status in premenopausal and no effect in postmenopausal subjects. Further
      studies are required to ascertain the role these dietary compounds may have to
      play in breast cancer prevention.

PMID- 14679384
TI  - Predictors of abdominal obesity among 31-y-old men and women born in Northern
      Finland in 1966.
AB  - OBJECTIVE: To find predictors of abdominal obesity (defined by >90th percentile
      of waist/hip ratio (WHR)) and related factors among 31-y-old men and women.
      DESIGN: Longitudinal study of the northern Finland birth cohort of 1966 with
      measurements obtained at birth, 14 and 31 y. SUBJECTS: A total of 2841 men and
      2930 women with data on WHR at 31 y. RESULTS: The most important predictor of
      abdominal obesity among the 31-y-old men was a high body mass index (BMI), those
      with normal weight at 14 y who were obese at 31 y having an especially high risk
      of abdominal obesity at 31 y. Abdominal obesity was independently associated with
      current weight status, small size for gestational age, a high intake of alcohol
      at 31 y, physical inactivity at 31 y, unhealthy diet in the sense of infrequent
      consumption of fiber-rich foods and frequent consumption of sausages, and a low
      level of occupational training. Physical inactivity and minimal vocational
      training also tended to be associated with abdominal obesity among women. The
      analyses were controlled for maternal age and BMI, and also for hormonal
      contraception and parity among women. CONCLUSIONS: Some aspects of risk of adult
      abdominal obesity were evident during adolescence, and good advice is needed
      then, and in early adulthood, in order to reduce the risk of abdominal obesity in
      their thirties. Those who are small for gestational age are vulnerable to the
      development of abdominal obesity. Successful weight control from adolescence to
      adulthood, and healthy eating, alcohol drinking and exercise habits are important
      for avoiding abdominal accumulation of body fat.

PMID- 14679385
TI  - New dietary reference intakes in the Netherlands for energy, proteins, fats and
      digestible carbohydrates.

PMID- 14679386
TI  - Differential brain activity in alcoholics and social drinkers to alcohol cues:
      relationship to craving.
AB  - Using fMRI, our group previously found that after a sip of alcohol and exposure
      to alcohol beverage pictures, alcoholics compared to social drinkers had
      increased differential brain activity in the prefrontal cortex and anterior
      thalamus. This study extends this earlier work with several improvements
      including imaging the entire brain (rather than the anterior half previously) and
      recording craving, while the subjects viewed images within the scanner. In a
      Philips 1.5 T MRI scanner, 10 nontreatment-seeking alcoholics and 10 age-matched
      healthy social drinkers were given a sip of alcohol before viewing a 12 min
      randomized presentation of pictures of alcoholic beverages, nonalcoholic
      beverages, and two different visual control tasks. During picture presentation,
      changes in regional brain activity were measured in 15 transverse T2(*)-weighted
      blood oxygen level dependent slices. Subjects rated their urge to drink after
      each picture sequence. After a sip of alcohol, while viewing alcohol cues
      compared to viewing other beverage cues, the alcoholics, but not social drinkers,
      reported higher craving ratings and had increased activity in the prefrontal
      cortex and anterior limbic regions. Brain activity in the left nucleus accumbens,
      anterior cingulate, and left orbitofrontal cortex significantly correlated with
      subjective craving ratings in alcohol subjects but not in control subjects. This
      study suggests, as did our earlier study, that alcoholics and not social
      drinkers, when exposed to alcohol cues, have increased brain activity in areas
      that reportedly subserve craving for other addictive substances.

PMID- 14679387
TI  - Using fMRI to quantify the time dependence of remifentanil analgesia in the human
      brain.
AB  - To understand and exploit centrally acting drugs requires reliable measures of
      their time course of action in the human brain. Functional magnetic resonance
      imaging (fMRI) is able to measure noninvasively, drug-induced changes in task
      related brain activity. Here, we have characterized, in a specific region of the
      brain, the time of onset of action and the half-life of action of a clinically
      relevant dose of a potent opioid analgesic agent, remifentanil. These times were
      established from the temporal variation of the amplitude of the blood oxygen
      level-dependent response in the insular cortex contralateral to a painfully hot
      thermal stimulus, in volunteers receiving a remifentanil infusion. The insular
      cortex has repeatedly been reported as activated by noxious thermal stimulation.
      The times of onset and offset of drug action were each characterized by a half
      life for changes in fMRI signal from within the insula. These characteristic
      times agreed with the observed drug-induced analgesia and previous
      pharmacokinetic-pharmacodynamic measurements for remifentanil. We have
      successfully measured, for the first time using fMRI, temporal pharmacological
      parameters for a CNS-active drug based on its effect on task-related activity in
      a specific brain region. Comparison of the time course of regional brain activity
      with pain perception could reveal those regions engaged in drug-induced
      analgesia.

PMID- 14679389
TI  - Gene flow, historical population dynamics and genetic diversity within French
      Guianan populations of a rainforest tree species, Vouacapoua americana.
AB  - Both gene flow and historical events influence the genetic diversity of natural
      populations. One way to understand their respective impact is to analyze
      population genetic structure at large spatial scales. We studied the distribution
      of genetic diversity of 17 populations of Vouacapoua americana (Caesalpiniaceae)
      in French Guiana, using nine microsatellite loci. Low genetic diversity was
      observed within populations, with a mean allelic richness and gene diversity of
      4.1 and 0.506, respectively, which could be due to low effective population size
      and/or past bottlenecks. Using the regression between Fst/(1-Fst), estimated
      between pairs of populations, and the logarithm of the geographical distance, the
      spatial genetic structure can partly be explained by isolation-by-distance and
      limited gene flow among populations. This result is in agreement with the
      species' biology, including seed and pollen dispersal by rodents and insects,
      respectively. In contrast, no clear genetic signal of historical events was found
      when examining genetic differentiation among populations in relation to
      biogeographical hypotheses or by testing for bottlenecks within populations. Our
      conclusion is that nuclear spatial genetic structure of V. americana, at the
      geographic scale of French Guiana, is better explained by gene flow rather than
      by historical events.

PMID- 14679390
TI  - Population genetic structure of a colonising, triploid weed, Hieracium lepidulum.
AB  - Understanding the breeding system and population genetic structure of invasive
      weed species is important for biocontrol, and contributes to our understanding of
      the evolutionary processes associated with invasions. Hieracium lepidulum is an
      invasive weed in New Zealand, colonising a diverse range of habitats including
      native Nothofagus forest, pine plantations, scrubland and tussock grassland. It
      is competing with native subalpine and alpine grassland and herbfield vegetation.
      H. lepidulum is a triploid, diplosporous apomict, so theoretically all seed is
      clonal, and there is limited potential for the creation of variation through
      recombination. We used intersimple sequence repeats (ISSRs) to determine the
      population genetic structure of New Zealand populations of H. lepidulum. ISSR
      analysis of five populations from two regions in the South Island demonstrated
      high intrapopulation genotypic diversity, and high interpopulation genetic
      structuring; PhiST = 0.54 over all five populations. No private alleles were
      found in any of the five populations, and allelic differentiation was correlated
      to geographic distance. Cladistic compatibility analysis indicated that both
      recombination and mutation were important in the creation of genotypic diversity.
      Our data will contribute to any biocontrol program developed for H. lepidulum. It
      will also be a baseline data set for future comparisons of genetic structure
      during the course of H. lepidulum invasions.

PMID- 14679391
TI  - Fine-scale genetic structure of grape phylloxera from the roots and leaves of
      Vitis.
AB  - Patterns of variation at microsatellite loci suggest that root populations of the
      pest grape phylloxera (Daktulosphaira vitifoliae) are largely parthenogenetic in
      Australian vineyards. To investigate reproduction in leaf galling phylloxera and
      the association between these individuals and phylloxera on roots, we examined in
      detail genetic variation in phylloxera from a vineyard block. Some genotypes
      found on leaf galls within this block were not present on roots, whereas others
      spanned both zones. There was no evidence that genotypes on roots were the
      product of sexual reproduction in leaf galls. mtDNA variation was not associated
      with the location of the phylloxera clones. The spatial distribution of genotypes
      within a root population was further investigated by intensively sampling
      phylloxera from another vineyard block. Join-count spatial autocorrelation
      statistics were used to explore fine-scale spatial structure. Clones were
      nonrandomly distributed within the block and there was evidence that the
      distribution of clones followed rows. These findings suggest firstly that there
      is limited dispersal of root and leaf feeding phylloxera, and secondly that
      factors, other than vine host, are likely to be important and contribute to
      clonal structure within populations.

PMID- 14679392
TI  - A study of association between genetic markers in candidate genes and
      reproductive traits in one generation of a commercial broiler breeder hen
      population.
AB  - Markers of alleles for three physiological candidate genes for reproductive
      traits, growth hormone (GHR), gonadotropin-releasing hormone receptor (GNRHR) and
      neuropeptide Y (NPY) were assessed for the association with the total egg
      production, number of double-yolked eggs and age at first egg in a single
      generation of a broiler breeder (Gallus gallus) pedigree dam line. Single
      nucleotide polymorphisms and deletions were detected in the GHR, GNRHR and NPY
      genes. Genotypes were identified using a PCR-RFLP assay. The frequency of
      restriction enzyme+/-alleles in the population was for GHR 0.68 (NspI-) and 0.32
      (NspI+), for NPY 0.78 (DraI+) and 0.22 (DraI-) and for GNRHR 0.54 (Bpu1102I+) and
      0.46 (Bpu1102I-). Trait data from a total of 772 hens in 67 sire families from
      one generation of the pedigree dam line were recorded. However, the analysis used
      only the offspring of heterozygous sires to reduce the influence of selection and
      genetic background (n=33 sire families for GHR; n=14 sire families for NPY; n=36
      sire families for GNRHR). A dominance effect of NPY on age at first egg and an
      additive effect of GNRHR on the number of double-yolked eggs were found (P<0.05).

PMID- 14679393
TI  - Heat and cold-induced male sterility in Drosophila buzzatii: genetic variation
      among populations for the duration of sterility.
AB  - Here we studied three phenotypic traits in Drosophila buzzatii that are strongly
      effected by temperature, and are expected to be closely associated with fitness
      in nature. The traits measured were thermal threshold of male sterility, time for
      males to gain fertility when reared at a sterility-inducing temperature and
      transferred to 25 degrees C on eclosion and survival after development. The last
      two traits were measured under four temperature regimes, constant 12 degrees C,
      25 degrees C, 31 degrees C, and fluctuating 25 degrees C (18 h) and 38 degrees C
      (6 h). We looked for genetic variation in these traits and relations among them
      in four lines of D. buzzatii originating from Argentina and Tenerife. The thermal
      threshold of heat-induced male sterility was found to lie within the range of
      30.0-31.0 degrees C. When measuring the time for males to gain fertility, males
      reared at a nonstressful temperature (25 degrees C) were fertile 58-67 h after
      emergence with only minor differences among lines. When reared constant 31
      degrees C, males were fertile 174-225 h after hatching. The Argentinean lines
      were significantly faster in recovering from sterility than were the lines from
      Tenerife. When reared in a fluctuating temperature regime, differences among
      lines increased, dividing the lines into three significantly different groups,
      with a sterility period of 135-215 h. When reared at 12 degrees C from the pupal
      stage, males were fertile after 106-130 h with significant difference in the
      variance but not in the mean duration of sterility. Significant differences in
      viability were found among development temperatures, but not among lines, and
      viability and the duration of sterility seem to be genetically independent.

PMID- 14679394
TI  - QTL analysis of variation in male courtship song characters in Drosophila
      virilis.
AB  - We have used a quantitative trait locus (QTL) mapping approach to study the
      genetic basis of differences between two Drosophila virilis strains representing
      extreme phenotypes in two song characters, the number of pulses in a pulse train
      (PN) and the length of a pulse train (PTL). Variation in these characters among
      520 F2 males was studied by single-marker analysis and composite interval mapping
      (CIM) using a recombination linkage map constructed for 26 microsatellite
      markers. In single-marker analysis, two adjacent microsatellite markers on the
      third chromosome, msat19 and vir84 explained 13.8 and 12.4% of the variation in
      PN and 9.9 and 6.5% of the variation in PTL, respectively. CIM analysis revealed
      significant QTLs affecting PN, located on the X and the second, third and fourth
      chromosome of D. virilis, while variation in PTL was attributable to QTLs located
      only on the third chromosome.

PMID- 14679395
TI  - Mating system and gene flow in the red seaweed Gracilaria gracilis: effect of
      haploid-diploid life history and intertidal rocky shore landscape on fine-scale
      genetic structure.
AB  - The impact of haploid-diploidy and the intertidal landscape on a fine-scale
      genetic structure was explored in a red seaweed Gracilaria gracilis. The pattern
      of genetic structure was compared in haploid and diploid stages at a
      microgeographic scale (< 5 km): a total of 280 haploid and 296 diploid
      individuals located in six discrete, scattered rock pools were genotyped using
      seven microsatellite loci. Contrary to the theoretical expectation of
      predominantly endogamous mating systems in haploid-diploid organisms, G. gracilis
      showed a clearly allogamous mating system. Although within-population allele
      frequencies were similar between haploids and diploids, genetic differentiation
      among haploids was more than twice that of diploids, suggesting that there may be
      a lag between migration and (local) breeding due to the long generation times in
      G. gracilis. Weak, but significant, population differentiation was detected in
      both haploids and diploids and varied with landscape features, and not with
      geographic distance. Using an assignment test, we establish that effective
      migration rates varied according to height on the shore. In this intertidal
      species, biased spore dispersal may occur during the transport of spores and
      gametes at low tide when small streams flow from high- to lower-shore pools. The
      longevity of both haploid and diploid free-living stages and the long generation
      times typical of G. gracilis populations may promote the observed pattern of high
      genetic diversity within populations relative to that among populations.

PMID- 14679396
TI  - Changes in mortality patterns and temperature dependence of lifespan in
      Drosophila melanogaster caused by inbreeding.
AB  - After an inbreeding event, lifespan can be curtailed through the expression of
      deleterious alleles. This will impact on both mortality patterns and interactions
      with the environment as visualised in reaction norms. We have established the
      effects of inbreeding on the temperature dependence of lifespan and on mortality
      patterns in Drosophila melanogaster. Four inbred lines displaying severely
      decreased lifespan and five outbred controls were assessed for male adult
      survival at three temperatures. As expected, all inbred lines showed a shorter
      lifespan than noninbred lines. The mechanisms behind this, however, appeared to
      be very diverse. Two inbred lines showed a significantly decreased temperature
      dependence of lifespan compared to the control lines. Analysis of variance on the
      mortality parameters over all lines showed that inbreeding changes the age
      independent mortality but not the age-dependent mortality, whereas temperature
      does the opposite. This suggests that gene-by-environment interaction caused by
      inbreeding is the result of changes in the processes of lifespan determination.
      Importantly, for the two other inbred lines, a particular temperature regime
      triggered the expression of conditional lethal alleles. Mortality was
      concentrated in short lethal phases early in adult life. These conditionally
      expressed lethal alleles affecting lifespan demonstrate line specificity for
      inbreeding depression and will help ageing studies as such alleles may serve as
      candidate genes for ageing processes and age-related pathologies in humans.

PMID- 14679397
TI  - Minimum prevalence, birth incidence and cause of death for Prader-Willi syndrome
      in Flanders.
AB  - The identification of all people with a diagnosis of Prader-Willi syndrome (PWS)
      confirmed by DNA methylation analysis living in Flanders was attempted through
      contact with the four genetic centres and the PWS Association. The birth
      incidence for the period 1993-2001 was 1:26 676, the minimum prevalence at 31
      December 2001 was 1:76 574. A decreasing number of cases with age was found,
      which can be explained by a number of missing cases in the older population, a
      higher neonatal mortality in the past and an increasing mortality with age.
      Childhood death is usually sudden and associated with respiratory infection and
      high temperature, while the cause of death in adults is considered to be
      circulatory or respiratory in origin.

PMID- 14679398
TI  - Annexin V assay-proven anti-apoptotic effect of ascorbic acid 2-glucoside after
      cold ischemia/reperfusion injury in rat liver transplantation.
AB  - Controversy exists over whether the predominant cell death of hepatocytes is due
      to apoptosis or necrosis after ischemia/reperfusion injury. In this study we
      investigated the predominant cell death of hepatocytes after cold
      ischemia/reperfusion injury using the Annexin V-based assay, and evaluated the
      anti-apoptotic effect of ascorbic acid 2-glucoside (AA-2G) added to the
      University of Wisconsin solution (UW solution) in rat liver transplantation. The
      retrieved liver was preserved in 4 UW solution for 24 h, and then transplanted
      orthotopically to the syngeneic Wistar recipient. The animals were divided into 2
      groups, a control group (n=10), in which liver grafts were preserved in UW
      solution (4), and an AA-2G group (n=10), in which liver grafts were preserved in
      UW solution (4) with AA-2G (100 ug/ml). The serum AST level 4 h after reperfusion
      in the control group was significantly suppressed in the AA-2G group, and the
      bile production of the liver graft in the AA-2G group was well recovered. The
      mean survival time in the AA-2G group was significantly improved compared with
      that in the control group. Annexin-V and Propidium iodide staining 4 h after
      reperfusion showed a significantly higher percentage of viable hepatocytes in the
      AA-2G group compared with the control group (93.4 +/- 2.0 vs. 80.3 +- 2.1%,
      P<0.05). In the control group, the main cell death of hepatocytes was apoptosis
      (early apoptosis: 10.0 +- 4.7%, late apoptosis: 6.4 +/- 1.7%). The addition of AA
      2G to the UW solution significantly inhibited both early and late apoptotic cell
      death 4 h after reperfusion (early apoptosis: 0.98 +/- 0.88%, late apoptosis: 2.2
      +/- 1.1%). The expression of caspase 9 in the immunostaining of the liver graft
      was suppressed in the AA-2G group compared with in the control group. Our study
      using the Annexin V-based assay provided evidence that the predominant cell death
      of hepatocytes was apoptosis after 24 h cold ischemia/reperfusion injury in rat
      liver transplantation. The addition of AA-2G to the UW solution attenuated 24 h
      cold ischemia/reperfusion injury by inhibiting the apoptosis of hepatocytes.

PMID- 14679399
TI  - Anti-viral actions and viral dynamics in the early phase of three different
      regimens of interferon treatment for chronic hepatitis C: differences between the
      twice-daily administration of interferon-beta treatment and the combination
      therapy with interferon-alpha plus ribavirin.
AB  - To improve the efficacy of interferon (IFN) treatment for chronic hepatitis C, we
      have proposed the twice-daily administration of IFN-beta as a promising induction
      therapy. In this study, we demonstrated differences between the clearance of
      circulating HCV-RNA and the induction of anti-viral actions during the first 2
      weeks of treatment. Nine patients with a high viral load and genotype 1b were
      randomly assigned to 3 groups: group A received 3MU of IFN-beta twice a day at
      intervals of 5 and 19 h; group B received 3MU of IFN-beta twice a day at
      intervals of 10 and 14 h; group C received 6MU of IFN-alpha once a day with
      ribavirin. The expression of OAS2, PKR, and MxA in peripheral blood mononuclear
      cells (PBMCs) were quantified by real-time polymerase chain reaction method. The
      viral clearance showed a bi-phasic pattern, and those in the second phase of
      groups A and B were significantly steeper than that of group C. The peak level of
      OAS2 during the first phase was correlated with the first phase decay. The MxA
      expression tended to be higher in group A and B than in group C. The expression
      of these 3 proteins tended to decrease at day 6 in group C, but increase in
      groups A and B. These might make differences in the viral decay during the second
      phase

PMID- 14679400
TI  - Percutaneous sclerotherapy for venous malformations using polidocanol under
      fluoroscopy.
AB  - This retrospective study evaluated the safety and efficacy of using polidocanol
      with X-ray fluoroscopy for percutaneous sclerotherapy of venous malformations of
      the limbs, head, and neck. The subjects were 16 of 18 patients who presented to
      our department with venous malformations. Two patients were excluded because they
      were unlikely to benefit from the treatment. Of the 16 included in the study, 1
      could not be treated because of inaccessibility, and another was lost to follow
      up. Among the 14 cases that we were able to follow-up, 11 cases had had pain as
      their primary symptom. Following treatment, this symptom remained unchanged in 1
      patient, was improved in 4, and had disappeared in 6; however, there was a
      recurrence of pain for 3 of these patients. Two patients had sought treatment for
      cosmetic purposes; following treatment, the lesion disappeared in one and showed
      a significant reduction in the other. The remaining patient presented with a
      primary symptom of mouth bleeding, which disappeared following treatment. There
      were no critical complications. Percutaneous sclerotherapy of venous
      malformations using polidocanol is safe and effective, and permits repeat
      treatments. The efficacy is especially good for resolving pain, and complications
      are minor. It is desirable to use fluoroscopy for these procedures

PMID- 14679401
TI  - Cutaneous manifestations of anthrax in Eastern Anatolia: a review of 39 cases.
AB  - Anthrax is essentially a disease of grazing herbivorous animals. The most common
      form of the disease is cutaneous anthrax, which accounts for 95% of all cases. We
      report here 39 cutaneous anthrax cases in humans that were seen in Eastern
      Anatolia over a six-year period. The clinical presentation was malignant edema in
      16 of the cases (41%) and malignant pustule in 23 (59%). A secondary bacterial
      infection was present in 13 patients (33.3%) in the vicinity of the lesions. The
      agent was observed using Gram-stained smears in 25 patients (64%), and Bacillus
      anthracis was isolated from 15 patients (38.5%). All of the patients were treated
      with penicillin G or penicillin procaine, except one patient who had a penicillin
      allergy. One patient with cervical edema (2.5%) died as a result of laryngeal
      edema and sepsis syndrome. In conclusion, we found that the appearance of the
      skin lesion of cutaneous anthrax may vary, and this fact, combined with the
      rarity of this disease, which contributes to a general lack of experience among
      medical personnel, may make diagnosis difficult in nonagricultural settings

PMID- 14679402
TI  - Experimental study of the pathogenesis of moyamoya disease: histological changes
      in the arterial wall caused by immunological reactions in monkeys.
AB  - Moyamoya disease is a progressive vascular disorder of unknown etiology. Theories
      of inflammatory and immunologic mechanisms have been proposed as the
      pathogeneses. We have designed a new method of administering N-acetylmuramyl-L
      alanyl-D-isoglutamine (MDP) for experimental induction of moyamoya disease using
      an intravascular interventional technique combined with rod-shaped embolic
      materials made from lactic acid-glycolic acid copolymer. The embolic materials
      containing MDP were repeatedly injected into the right internal carotid artery of
      monkeys in the embolic group. Intravenous injections of MDP solution alone were
      performed in the intravenous group. Histological examination of the arteries
      demonstrated reduplication and lamination of the internal elastic laminae, which
      corresponded with findings of moyamoya disease in both groups. These histological
      changes occurred not only in the intracranial arteries on the embolization side,
      but also in the contralateral intracranial and even extracranial arteries. The
      changes were more prominent in the intravenous group than in the embolic group.
      We conclude that the systemic humoral factors induced by MDP in this study may be
      important in the pathogeneses of moyamoya disease. Our observations suggest that
      moyamoya disease is a systemic vascular disease and has an etiologic factor
      affecting both intracranial and extracranial arteries

PMID- 14679403
TI  - Formation of meso, N-diphenylprotoporphyrin IX by an aerobic reaction of
      phenylhydrazine with oxyhemoglobins.
AB  - Administration of phenylhydrazine to rabbits resulted in the denaturation of
      hemoglobins in erythrocytes, causing the formation of intracellular precipitates
      known as Heinz bodies, severe hemolytic anemia, and reticulocytosis. To elucidate
      the molecular mechanism of the destabilization, we allowed human oxyhemoglobins
      to react aerobically with phenylhydrazine. After treatment with acetic acid/HCl
      and H2SO4/methanol, the chloroform extract contained blue-green pigments of major
      products accompanied by different minor products. Each product was isolated by
      column chromatography. By fast-atom-bombardment mass spectrometry (FAB-MS) and
      proton nuclear magnetic resonance (1H-NMR) spectrometry, dimethyl esters of N
      phenylprotoporphyrin IX and meso, N-diphenylprotoporphyrin IX were determined.
      Other major products also were determined to be dimethyl esters of triphenyl-and
      tetraphenyl-substituted protoporphyrins by FAB-MS. The formation of meso, N
      diphenylprotoporphyrin indicated that the addition of a phenyl radical to the
      meso-carbon atom of the protoporphyrin ring occurred. Triphenyl and tetraphenyl
      adducts also indicated the formation of phenyl radicals in the aerobic reaction
      of phenylhydrazine with oxyhemoglobins. From these results, we suggest that the
      formation of phenyl radicals and the replacement of heme with phenyl-substituted
      protoporphyrins cause the destabilization of hemoglobins to induce Heinz bodies
      and hemolytic anemia with phenylhydrazine.

PMID- 14679404
TI  - A simple method for screening photoelectric dyes towards their use for retinal
      prostheses.
AB  - Photoelectric dyes absorb light and convert photon energy to electric potentials.
      To test whether these dyes could be used for retinal prostheses, a simple in
      vitro screening system was developed. Retinal neurons were cultured from the eyes
      of chick embryos at the 10-day embryonic stage, at which time no retinal
      photoreceptor cells have yet developed. Intracellular calcium elevation was
      observed with Fluo-4 in cultured retinal neurons before and after photoelectric
      dye was applied at varying concentrations to the culture medium. Five of 7
      photoelectric dyes tested in this in vitro system induced intracellular calcium
      elevation in cultured chick retinal neurons. The intracellular calcium elevation
      generated by the 5 photoelectric dyes was blocked by extracellular calcium
      depletion in the case of all 5 dyes, and, except for one dye, by the presence of
      voltage-gated calcium channel blockers. The photoelectric dyes absorbed light
      under an inverted microscope and stimulated retinal neurons. This simple in vitro
      system allows the screening of photoelectric dyes which can be used for retinal
      prostheses.

PMID- 14679405
TI  - Survey of the stray dog population and the health education program on the
      prevention of dog bites and dog-acquired infections: a comparative study in Nepal
      and Okayama Prefecture, Japan.
AB  - We estimated the number of stray dogs in Kathmandu, Nepal, where human rabies
      cases still occur, and in Shimotsui, Okayama Prefecture, Japan. In Kathmandu, the
      stray dog density was 2,930 stray dogs/km2, and the ratio of stray dogs to humans
      was 1:4.7. In Shimotsui, the density was 225 stray dogs/km2, and the ratio was
      1:5.2. Since the stray dog population in Nepal is very large, one of the measures
      used to prevent dog bites and dog-acquired infections such as rabies is an effort
      to capture stray dogs. Another such measure is an effort to decrease the
      availability of food for stray dogs. We also organized health education programs
      in both Nepal and Okayama Prefecture, Japan, which involved a course on the
      prevention of dog bites and subsequent infections. After each course, a
      questionnaire survey was conducted. The results suggest that the course
      participants understood these important preventive methods. In addition to the
      measures mentioned above and the routine vaccination of dogs, this health
      education course is recommended as a long-term preventive program

PMID- 14679406
TI  - The benefits of smoking cessation.

PMID- 14679407
TI  - Adjustable maintenance dosing with budesonide/formoterol reduces asthma
      exacerbations compared with traditional fixed dosing: a five-month multicentre
      Canadian study.
AB  - BACKGROUND: Adjustable maintenance dosing with budesonide/formoterol in a single
      inhaler (Symbicort, AstraZeneca, Lund, Sweden) may provide a convenient means of
      maintaining asthma control with the minimum effective medication level.
      OBJECTIVES: To compare adjustable and fixed maintenance dosing regimens of
      budesonide/formoterol in asthma. METHODS: This was an open-label, randomized,
      parallel-group, multicentre, Canadian study of asthma patients (aged 12 years or
      older, postbronchodilator forced expiratory volume in 1 s 70% or greater of
      predicted normal). Following a one-month run-in on budesonide/formoterol (100/6
      ug or 200/6 ug metered doses, two inhalations twice daily), 995 patients were
      randomly assigned either to continue on this fixed dosing regimen or to receive
      budesonide/formoterol adjustable dosing (step down to one inhalation twice daily
      if symptoms were controlled or temporarily step up to four inhalations twice
      daily for seven or 14 days if asthma worsened). The primary efficacy variable was
      the occurrence of exacerbations (requiring oral or inhaled corticosteroids,
      emergency department treatment, serious adverse events or added maintenance
      therapy because of asthma). RESULTS: With adjustable dosing, significantly fewer
      patients experienced exacerbations compared with fixed dosing (4.0% versus 8.9%,
      P=0.002; number needed to treat=21 [95% CI 13 to 59]). Patients required 36%
      fewer overall doses of budesonide/formoterol (2.5 versus 3.9 inhalations/day,
      P<0.001), and total costs per patient were lower (difference over five months 
      141 Canadian dollars [95% CI -162 Canadian dollars to -116 Canadian dollars]).
      Asthma symptom severity (modified National Heart, Lung, and Blood Institute
      stage) was maintained or improved in 97% or greater of patients in both groups
      (pre-run-in to end of treatment). Both treatments were well tolerated.
      CONCLUSIONS: Budesonide/formoterol adjustable maintenance dosing provided more
      effective asthma control than fixed dosing, with a lower overall drug dose and
      reduced total cost.

PMID- 14679408
TI  - The descriptive epidemiology of primary lung cancer in an Alberta cohort with a
      multivariate analysis of survival to two years.
AB  - BACKGROUND: Lung cancer contributes significantly to cancer morbidity and
      mortality. Although case fatality rates have not changed significantly over the
      past few decades, there have been advances in the diagnosis, staging and
      management of lung cancer. OBJECTIVE: To describe the epidemiology of primary
      lung cancer in an Alberta cohort with an analysis of factors contributing to
      survival to two years. PATIENTS AND METHODS: Six hundred eleven Albertans
      diagnosed with primary lung cancer in 1998 were identified through the Alberta
      Cancer Registry. Through a chart review, demographic and clinical data were
      collected for a period of up to two years from the date of diagnosis. RESULTS:
      The mean age at diagnosis was 66.5 years. The majority of cases (92%) were
      smokers. Adenocarcinoma, followed by squamous cell carcinoma, were the most
      frequent nonsmall cell lung cancer histologies. Adenocarcinoma was more frequent
      in women, and squamous cell carcinoma was more frequent in men. The overall two-
      year survival rates for nonsmall cell, small cell and other lung cancers were
      24%, 10% and 13%, respectively. In multivariate analysis, stage, thoracic surgery
      and chemotherapy were significantly associated with survival to two years in
      nonsmall cell carcinoma; only stage and chemotherapy were significant in small
      cell carcinoma. CONCLUSIONS: This study provides a Canadian epidemiological
      perspective, which generally concurs with the North American literature.
      Continued monitoring of the epidemiology of lung cancer is essential to evaluate
      the impact of advances in the diagnosis, staging and management of lung cancer.
      Further clinical and economic analysis, based on data collected on this cohort,
      is planned.

PMID- 14679409
TI  - Computed tomography and bronchoscopy in endobronchial tuberculosis.
AB  - BACKGROUND: The therapeutic response to endobronchial tuberculosis is usually
      evaluated by bronchoscopy. Currently, there are no published studies
      investigating the use of computed tomography for the evaluation of therapeutic
      response in endobronchial tuberculosis. OBJECTIVE: A retrospective study was
      performed to evaluate the bronchoscopic and computed tomographic features of
      endobronchial tuberculosis before and after treatment. The aim of this study was
      to investigate the usefulness of computed tomography for the assessment of
      treatment. METHODS: The clinical, pathological and bronchoscopic features of
      endobronchial tuberculosis were evaluated in 55 patients. The age range of the
      patients was 21 to 52 years. Computed tomography and bronchoscopy were performed
      before and after treatment. RESULTS: Diagnosis of tuberculosis was confirmed by
      culture and histopathological examination. Bronchoscopic examination revealed 89
      endobronchial lesions of various types in 55 patients. The exudative type was the
      most common. Follow-up bronchoscopy revealed that exudative-, ulcerative- and
      granular-type lesions healed completely. Computed tomography performed after
      treatment correlated well with the follow-up bronchoscopic findings. CONCLUSION:
      The results suggest that follow-up computed tomography is useful for the
      evaluation of therapeutic response and complications associated with
      endobronchial tuberculosis, and may replace bronchoscopy.

PMID- 14679410
TI  - Diffuse panbronchiolitis in a Caucasian man in Canada.
AB  - Diffuse panbronchiolitis (DPB) is a rare, chronic bronchiolar disease in non
      Asian populations and is therefore commonly overlooked in Western countries. It
      usually affects nonsmokers and manifests as persistent air flow obstruction,
      chronic cough and interstitial nodular opacities. Untreated, the prognosis is
      poor. In this report the authors describe a Caucasian man of Canadian descent who
      presented with progressive clinical and lung function impairment despite three
      years of bronchodilator and corticosteroid treatment with presumed asthma. His
      chest computed tomography scan showed diffuse centrilobular opacities. Lung
      biopsy revealed chronic bronchiolitis characterized by infiltration of
      lymphocytes, plasma cells and foam cells in respiratory and terminal bronchioles,
      compatible with a diagnosis of DPB. After two months of therapy with
      clarithromycin, the patient had already shown improvement. Physicians should be
      aware that DPB may occur in Western countries, and that DPB should be considered
      in the differential diagnosis of patients with persistent air flow obstruction
      and nodular shadows on chest radiograms.

PMID- 14679411
TI  - The chronic need to improve the management of pain.

PMID- 14679412
TI  - Attitudes toward opioid use for chronic pain: a Canadian physician survey.
AB  - OBJECTIVES: To measure chronic pain patient volumes seen in primary care
      practice; to determine what medications physicians choose for the treatment of
      moderate to severe chronic pain; to identify barriers to the use of opioids in
      the treatment of chronic pain; and to assess physicians' attitudes toward the
      current management of chronic pain in Canada. DESIGN: A computer-assisted
      telephone survey of 100 regionally representative Canadian physicians with a
      defined interest in palliative care (PC, n=30) or noncancer pain (GP, n=70).
      SETTING: A survey was conducted by Ipsos-Reid in June 2001. Only physicians who
      met the eligibility criteria of having written 20 or more prescriptions for
      moderate to severe pain in the preceding four weeks or having devoted 20% of time
      to palliative care were eligible to participate. RESULTS: In one month, the
      average number of patients with moderate to severe chronic pain seen by PCs was
      94.2; the average seen by GPs was 44.7. The pain experienced by 83.3% of GP
      patients was noncancer related. For chronic cancer pain, an opioid analgesic was
      the treatment of choice of 79% of physicians (48% preferred morphine, 21%
      codeine, 10% other). For moderate to severe chronic noncancer pain, opioids were
      the first-line treatment of only 32% of physicians (16% preferred codeine, 16%
      major opioids) because a significant number preferred either non-steroidal anti
      inflammatory drugs (29%) or acetaminophen (16%). Thirty-five per cent of GPs and
      23% of PCs would never use opioids for noncancer pain, even when described as
      severe. Chronic pain was deemed by 68% of physicians to be inadequately managed.
      Almost 60% thought that pain management could be enhanced by improved physician
      education. Identified barriers to opioid use included addiction potential (37%)
      and side effects (25%). Seventeen per cent of GPs and 10% of PCs thought that
      regulatory sanctions limited opioid prescribing. CONCLUSIONS: Even among
      physicians experienced in chronic pain treatment, there is a reluctance to use
      opioids for severe nonmalignant pain. One-half of the survey participants
      believed that there was a need for improved physician education in pain
      management, including the use of opioids.

PMID- 14679413
TI  - Oral topical doxepin rinse: anesthetic effect in normal subjects.
AB  - Oral doxepin rinse has been reported to provide pain relief in patients with oral
      mucosal lesions due to cancer or cancer therapy. The purpose of this study was to
      assess the anesthetic effect of doxepin oral rinse in normal subjects to identify
      the duration of effect and to contrast the anesthetic effect with reported pain
      relief in patients with oral mucosal lesions. Normal volunteers were provided a
      solution of doxepin (5 mg/mL) for oral rinsing. Oral numbness and adverse effects
      were recorded for a period of 4 h after rinsing. Doxepin rinse resulted in
      mucosal anesthesia in all subjects. Sedation/fatigue was reported in four of
      seven subjects. There were no taste complaints and no nausea reported. The
      limited duration of numbness/anesthesia in normal subjects compared with prior
      studies showing pain relief for more than 3 h in patients with mucosal lesions,
      suggests that the extended duration of pain relief in patients was due to
      analgesic effects rather than anesthetic effects. The majority of normal subjects
      reported sedation after use, but this was less common in patients with mucosal
      lesions.

PMID- 14679414
TI  - Older adults with Alzheimer disease, comorbid arthritis and prescription of
      psychotropic medications.
AB  - OBJECTIVES: It is assumed that analgesia is underutilized among those with
      Alzheimer disease and that these patients may be inappropriately prescribed
      neuroleptics and benzodiazepines. The current study examines this assertion.
      DESIGN: For this study, prescription levels of analgesics and psychotropic
      medications for Alzheimer disease patients with (n=245) and without (n=215)
      musculoskeletal conditions (i.e., arthritis or rheumatism) are compared. SETTING:
      A national sample of community dwelling and institutionalized older adults was
      identified from the Canadian Study of Health and Aging (CSHA). PARTICIPANTS:
      Persons from 36 cities and surrounding rural areas over 64 years of age were
      randomly identified for the CSHA from government health records in all but one
      province. MEASUREMENTS: Prescribed analgesic and psychotropic medications were
      examined, as well as dementia severity and dementia related behavioural
      disturbance. RESULTS: Less than half of Alzheimer patients with arthritis or
      rheumatism were treated for pain (ie, 109 of 245 patients); they were also more
      likely to be prescribed benzodiazepines compared with Alzheimer patients without
      musculoskeletal conditions (subsequent to initial consideration for analgesia,
      dementia severity and dementia-related behaviours; Dchi(2)[Ddf =1] =3.97,
      P=0.046). CONCLUSIONS: These findings are in accord with prior research attesting
      to the undertreatment of pain among older adults. These results can be
      generalized with greater confidence, given the random composition of the patient
      sample.

PMID- 14679415
TI  - Comparing two observational systems in the assessment of knee pain.
AB  - OBJECTIVE: Research has demonstrated the utility of the Pain Behavior Measurement
      (PBM) system as a pain index. PBM involves the recording of sighing, rubbing,
      grimacing, guarding and bracing. A modification of this system has been proposed,
      focusing on the occurrence of joint flexing, rubbing, unloading the joint,
      guarding and rigidity, specifically for patients with knee pain. The aim of the
      present study was to compare the original PBM to the modified version in a sample
      of knee replacement patients to assess the utility of the more specialized
      approach. It was expected that the more discomforting physiotherapy activities
      (knee bending and quadriceps exercises) would result in more pain behaviours than
      intermediate activities (walking and standing), which, in turn, would result in
      more pain behaviours than reclining. The extent to which each system reflected
      this expected pattern was examined. METHODS: Ninety-three seniors were observed
      while completing a series of structured post-knee surgery physiotherapy
      activities (knee bending, standing, walking, reclining and a quadriceps
      exercise). RESULTS: Analyses of self-reported levels of pain were consistent with
      the expected pattern of pain levels in relation to the physiotherapy activities.
      Specific pain behaviours within each system (eg, grimacing, rigidity) occurred in
      a manner consistent with the expected pattern, while other behaviours (e.g.,
      rubbing the affected area) did not. CONCLUSIONS: Although there was no clear
      advantage for the modified system over the PBM, an optimal approach may involve
      combining specific behaviours from each system.

PMID- 14679416
TI  - The effects of exposure to repeated minor pain during the neonatal period on
      formalin pain behaviour and thermal withdrawal latencies.
AB  - Preterm infants undergoing untreated, repeated painful procedures as part of
      their early experience are more likely to behave differently to pain as they
      mature than infants who were born at term and did not experience excessive
      exogenous pain. The neonatal rat model was used to investigate the short- and
      long-term effects of repeated pain in infancy on later development of pain
      responses. Newborn rat pups were randomly assigned by litter to be left unhandled
      (UH), handled by being removed from the dam for 15 min four times daily (H), and
      being handled and receiving pain from a paw prick with a 26G needle four times
      daily (P) on postnatal days (PD) 2 through 8 (PD2-PD8). Maternal behaviour and
      grooming of pups on their return to the nest were recorded at PD6 for H and P
      pups. At PD15, PD36 and PD65, animals were first tested for latency to thermal
      stimulation threshold using the Hargreaves test and then for inflammatory pain
      using the formalin test. Pups in the HP group received significantly more
      grooming from their mothers (359 s) than pups in the H group (295 s, P<0.0001).
      When accounting for differences in maternal grooming, a decreased thermal
      threshold in the P group compared with the H group (6.04 s versus 5.3 s, P<0.05)
      was found, although the correlations were not significant between maternal
      grooming and thermal thresholds. No group differences were seen with the formalin
      test. Interestingly, age was a significant factor in both tests, with younger
      animals showing fewer pain behaviours regardless of group or maternal grooming of
      the pup. Sex was significant at one age only in latency to thermal stimulation
      testing. The results suggest that changes in maternal care may be an important
      factor mediating the long-term effects of repeated neonatal experiences of pain.

PMID- 14679417
TI  - Treatment of chronic intractable neuropathic pain with dronabinol: case report of
      two adolescents.
AB  - OBJECTIVE: To evaluate the effectiveness of dronabinol for the treatment of
      neuropathic pain refractory to previous treatment. METHODS: We studied the
      response (reduction of pain intensity and functional improvement) to dronabinol
      (5 mg/day to 25 mg/day) in two adolescents with neuropathic pain and depression
      refractory to previous treatments over two and five years, respectively. RESULTS:
      Reduction in pain intensity (45%) was achieved in patient 2 and was unchanged in
      patient 1. Functional improvement was markedly increased in terms of academic
      performance, mood and sleep in both patients over four to five months, without
      major adverse effects. While these improvements dissipated over time, the
      patients were more reconnected with rehabilitation and focused less on the
      intrusiveness of their pain problem in their every day lives. CONCLUSIONS:
      Dronabinol appeared to be effective in improving pain affect and psychosocial
      functioning in the treatment of refractory neuropathic pain and may be considered
      as an adjuvant medication in the rehabilitation process. Well-controlled placebo
      studies are required for further evaluation.

PMID- 14679418
TI  - Temporal and geographic evolution of longstanding Crohn's disease over more than
      50 years.
AB  - Data on the natural history of longstanding Crohn's disease are very limited.
      After searching a clinical database of over 1000 patients with Crohn's disease,
      it was determined that eight patients (five women, three men) had disease
      documented for over 50 years. In spite of complex histories with either
      stricturing or penetrating complications, all currently have either no symptoms
      or minimal disease activity, often without the need for ongoing pharmacological
      treatment. Most significantly, their clinical courses were all characterized by
      prolonged asymptomatic periods, often for more than a decade, before the
      recurrence of symptomatic disease. Pathological findings in all patients revealed
      granulomatous inflammatory disease, often recurring intermittently over many
      decades. Moreover, the location of the findings implied that the disease has a
      tendency to evolve, not only in a temporal dimension, but also extending
      geographically within the gastrointestinal tract. These clinical and pathological
      features in longstanding Crohn's disease suggest that recurring or multiple
      discrete initiating events, rather than a single initiating event, could be
      involved in the etiology and pathogenesis of Crohn's disease.

PMID- 14679420
TI  - Ischemic colitis after weight-loss medication.
AB  - BACKGROUND: Previous weight-loss medications have received cautious support due
      to their association with pulmonary hypertension and valvular heart disease.
      However, newer drugs are increasingly being recommended as potentially safer and
      more efficacious. We report a case of ischemic colitis possibly linked to the use
      of a weight-loss drug, and review the literature to highlight an important latent
      consequence of these medications. CASE REPORT: A 59-year-old obese woman
      presented to the emergency room with rectal bleeding and suprapubic abdominal
      pain. Her medical history was unremarkable for risk factors for bowel ischemia.
      An appetite suppressant, phentermine 15 mg daily, had been prescribed, and had
      resulted in a 12 kg weight loss over 10 weeks. Colonoscopy and biopsies both
      demonstrated findings typical of mild ischemia at the splenic flexure.
      DISCUSSION: Phentermine, an amphetamine-derived sympathomimetic, acts centrally
      to suppress appetite. While there are no published reports linking the use of
      phentermine as a single agent to ischemic colitis, phentermine alone has been
      associated with ischemic neurological events and, when used in combination with
      fenfluramine, has been implicated in a single case of acute ischemic colitis.
      Other sympathomimetics, such as cocaine, have been clearly linked with ischemic
      colitis. CONCLUSIONS: This report describes a temporal association with the use
      of phentermine and the development of ischemic colitis. Heightened awareness and
      appropriate surveillance is warranted to determine whether the use of weight-loss
      drugs, such as phentermine, can lead to ischemic colitis.

PMID- 14679419
TI  - Ursodeoxycholic acid and atorvastatin in the treatment of nonalcoholic
      steatohepatitis.
AB  - BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is a serious disorder with
      the potential to gradually progress to cirrhosis. It is generally associated with
      obesity, diabetes and hyperlipidemia. Currently, there is no established therapy
      for NASH. The aim of the present study was to evaluate the effectiveness of
      atorvastatin and ursodeoxycholic acid (UDCA) in the treatment of NASH. METHODS:
      This prospective study included 44 adult patients (24 men, 20 women) with a mean
      age of 48.90+/-7.69 years and mean body mass index (BMI) of 29.40+/-3.82. Ten
      patients had a history of diabetes. Serological markers for viral hepatitis were
      negative in all patients and there was no history of alcohol or drug abuse.
      Patients who had autoimmune hepatitis were excluded from the study. Liver biopsy
      was performed before therapy to confirm the diagnosis. Among NASH patients, 17
      normolipidemic cases received UDCA 13 to 15 mg/kg/day (group 1), while
      hyperlipidemic cases (n=27) received atorvastatin 10 mg/day (group 2) for six
      months. The BMI, serum lipids, liver function tests and liver density, assessed
      by computerized tomography, were evaluated before and after the treatment period.
      The BMI, serum aminotransferase levels, histological parameters (steatosis,
      inflammation, fibrosis scores) and liver densities were not statistically
      different between the groups at the beginning of therapy. RESULTS: The BMI, serum
      glucose, and triglyceride levels did not change in either group after the
      treatment period. In group 1, serum alanine aminotransferase (ALT) and gamma
      glutamyl-transferase (GGT) levels reduced significantly, and in group 2, serum
      cholesterol, aspartate aminotransferase, ALT, alkaline phosphatase and GGT levels
      reduced significantly. Liver densities increased only in group 2, probably as a
      result of diminishing fat content of liver. The normalization of transaminases
      was also more prevalent in group 2. Liver steatosis was closely correlated with
      liver density, but inflammation and fibrosis were not. CONCLUSIONS: The use of
      atorvastatin in NASH patients with hyperlipidemia was found to be both effective
      and safe. The benefit of statin and UDCA therapy in normolipidemic patients with
      NASH requires confirmation with further placebo-controlled trials.

PMID- 14679421
TI  - Octreotide treatment of massive hemorrhage due to cytomegalovirus colitis.
AB  - Cytomegalovirus (CMV)-associated colitis can result in abdominal pain, diarrhea,
      significant blood loss and perforation. The standard therapy for CMV colitis
      includes supportive measures and antiviral medications. Severe hemorrhage due to
      CMV colitis often necessitates surgical resection. We present a case of a patient
      who was undergoing chemotherapy for acute B-cell lymphoblastic leukemia and
      developed significant abdominal pain and diarrhea followed by massive
      hematochezia. Colonoscopy showed numerous actively bleeding deep ulcers in the
      cecum. A provisional diagnosis of CMV colitis was made and she was started on
      ganciclovir. Histological assessment confirmed the diagnosis of CMV colitis. She
      continued to bleed profusely per rectum over the following five days, passing up
      to 1 L to 1.5 L of blood per day. She required 10 units of packed red blood cells
      over this time period. The patient refused surgical intervention and after
      discussion of possible options, octreotide was instituted. Her blood loss stopped
      almost immediately and she required no further transfusions. She tolerated the
      medication well and was discharged home at a later date in stable condition. This
      is the first reported case of the use of octreotide in the treatment of massive
      hematochezia from CMV colitis.

PMID- 14679422
TI  - Waiting-list induced proctitis: the hydrogen peroxide enema.
AB  - Hydrogen peroxide is a widely available disinfectant that has been reported to
      cause colitis. We report a case of a 67-year-old man who presented with an acute
      proctitis caused by a self-inflicted 3% hydrogen peroxide enema. The patient's
      intention was to cure himself of a recently diagnosed prostate cancer, because
      the waiting list for oncological consultation was deemed too long. The
      pathogenesis of hydrogen peroxide mucosal injury and a review of the literature
      is discussed.

PMID- 14679424
TI  - Use of LARA-urea breath test in the diagnosis of Helicobacter pylori infection in
      children and adolescents: a preliminary study.
AB  - BACKGROUND: An accurate diagnosis of Helicobacter pylori infection in children
      currently relies upon histological assessment or culture of gastric biopsies
      obtained at endoscopy. Noninvasive testing would permit simpler assessment of
      children with dyspeptic symptoms. The primary aim of the present study was to
      prospectively evaluate a novel urea breath testing method in children undergoing
      diagnostic assessment of dyspeptic symptoms and secondarily to consider the roles
      of other noninvasive tests in these children. METHODS: Laser associated ratio
      analysis (LARA)-13C urea breath testing was performed on children presenting with
      upper gastrointestinal symptoms for diagnostic endoscopy. Serum and stool were
      collected for performance of serology and stool antigen testing, respectively.
      Histology and culture of endoscopic biopsies of the gastric antrum were used to
      establish H pylori infection status. RESULTS: Eight (36%) of 22 children were H
      pylori-positive by histology or culture of gastric biopsies. Urea breath testing
      showed a sensitivity of 75%, but specificity of 100%. The deletion of a test meal
      from the urea breath test protocol in eight patients did not alter the utility of
      the test. Serology provided sensitivity of 87.5%, but a specificity of only 75%.
      Stool antigen testing in eight available samples provided sensitivity of 50% and
      specificity of 100%. CONCLUSIONS: The LARA-urea breath testing method provided
      less sensitivity in this group of children than suggested from previous studies.
      However, urea breath testing in children is easy to complete and provides rapid
      noninvasive results. Breath testing protocols require standardization; for
      instance, the addition of a test meal may not be necessary in older children.
      Although noninvasive tests for the presence of H pylori in children may provide
      accurate results and can be considered for use in the initial assessment of
      dyspeptic children, further work is required to establish the most accurate
      testing methods.

PMID- 14679425
TI  - Viral hepatitis in the Canadian Inuit and First Nations populations.
AB  - OBJECTIVE: To review published prevalence data regarding hepatitis A (HAV), B
      (HBV) and C (HCV) in Canadian Inuit and First Nations populations. METHODS:
      PubMed database search and review of all papers describing data derived from
      seroepidemiological surveys. RESULTS: The prevalence of anti-HAV positivity in
      Canadian Inuit and First Nations populations reported to date is high (range 75%
      to 95%) and approximately three times that of non-Aboriginal Canadians residing
      in the same communities. Among the Canadian Inuit, the prevalence of HBV
      infection is approximately 5%, or 20 times that of non-Aboriginal Canadians,
      while the risk of exposure to HBV is 25%, or five times higher. Regarding the
      First Nations population, preliminary data suggest the prevalences of HBV
      infection (0.3% to 3%) and exposure (10% to 22%) are similar to rates in non
      Aboriginals residing in the same regions and participating in similar high risk
      activities. Serological evidence of HCV infection (anti-HCV) is more common in
      the Canadian Inuit and First Nations (1% to 18%) than the remainder of the
      Canadian population (0.5% to 2%); however, viremia (HCV-RNA positivity) is less
      common (less than 5% versus 75% of anti-HCV positive individuals, respectively).
      CONCLUSIONS: Viral hepatitis is common in the Canadian Inuit and First Nations
      populations. In the absence of coexisting human immunodeficiency virus infection
      and alcohol abuse, the outcomes of HBV and HCV appear to be more benign than in
      non-Aboriginal Canadians.

PMID- 14679426
TI  - [Combinations of different cartilage resurfacing techniques].
AB  - AIM: The aim of this work was to control the results after simultaneous use of
      different modern resurfacing techniques. METHODS: We examined the patients who
      were subjected to different cartilage repair methods using the ICRS score
      (anterograde drilling, autologous chondrocytes transplantation, OATS, refixation
      with resorbable pins, spongious bone grafting, HTO). RESULTS: In two cases the
      combination of different cartilage regenerative methods in a one-step technique
      produced a good reconstruction of the joint surface with good clinical outcome.
      With the implantation of carbon plaques, osteolysis of the spongious bone in
      combination with an incomplete defect filling can be observed. The therapy must
      be individual and take the clinical, radiological and intraoperative findings
      into consideration. CONCLUSION: The combination of different resurfacing
      techniques may have success only if the biomechanical properties of the joint
      with axial malpositioning and ligament instabilities are considered and treated
      as well. New prospects are offered particularly for young patients with extensive
      cartilage damage and without other therapeutic options.

PMID- 14679427
TI  - [Radial shock wave therapy in calcifying tendinitis of the rotator cuff--a
      prospective study].
AB  - AIM: The aim of the study is to evaluate the influence of radial shock wave
      therapy (RSWT) on the course of calcifying tendinitis of the rotator cuff.
      MATERIAL AND METHODS: 35 patients with a mean age of 47.5 years suffering from
      calcifying tendinitis stage Gaertner 2 with a mean size of 16.6 mm in typical
      location (true-ap view) for a mean of 28 months were treated by low-energy RSWT
      three times. The acromio-humeral distance averaged 10.4 mm measured at the true
      ap view. All patients were clinically and radiologically followed-up at 4 weeks,
      3, 6 and 12 months after the last treatment. RESULTS: The Constant score improved
      significantly (p < 0.0001) during the first 4 weeks after RSWT from a mean of
      68.5 to a mean of 80.5 points and remained approximatively constant at 3, 6 and
      12 months follow-up. After 4 weeks 25.7% of the patients had no pain, 54.3%
      reported about pain relief. In the course of the follow-up a significant
      improvement of pain was observed: up to 80.8% painless and 19.2% pain relief 12
      months after RSWT. Radiologically 4 weeks after RSWT the X-ray examination showed
      in 17.6% no calcific deposit, in 20.5% a disintegration and in 61.5% no changes
      of the calcific deposit. At further follow-up we found a complete resorption of
      the calcific deposit in 75% up to 12 months after RSWT and 25% had no change in
      calcific deposit. Overall three patients (8.5%) had to undergo surgical treatment
      3-7 months after RSWT. CONCLUSION: The low-energy RSWT leads within the first 4
      weeks to a significant pain relief and an improvement of shoulder function. In
      consideration of the long history, the size and the spontaneous resorption rate
      of the calcific deposit, an inductive effect of RSWT on the resorption of the
      calcific deposit can be assumed.

PMID- 14679428
TI  - [Postoperatively recurring instability of the shoulder--a fault analysis in 46
      cases].
AB  - AIM: The successful operative stabilization of the shoulder joint is a demanding
      surgical procedure. The causality of shoulder instability is complex with in some
      cases multiple lesions in different anatomical structures. The surgeon has to
      understand the complexity of factors causing instability in order to be
      therapeutically successful. The aim of the study was to document the
      intraoperative pathology in revision instability surgery. METHOD: 46 patients
      with recurrent postoperative instability were included (8 female, 38 male, follow
      up > 12 months). After diagnostic arthroscopy an open revision surgery was
      performed in all cases. RESULTS: In 19 cases (40%) an insufficient surgical
      procedure was performed (inadequate capsular shift with worn out labral tissue).
      Selection of an incorrect surgical technique was the reason for revision in 12
      patients (25%). Anamnestically 5 patients reported a re-injury, whereas
      objectively only one patient described an adequate trauma. The most frequent
      finding was an open rotator interval (persisting Foramen Weitbrecht), which was
      seen in 22 cases (46%). CONCLUSION: A stable range of motion of the shoulder is
      achieved by a variety of different factors, which leads in most instances to a
      combination of pathological changes in case of a dislocated shoulder. To
      understand the contributing factors of an instable shoulder joint is a necessity
      to carry out a successful surgical procedure.

PMID- 14679429
TI  - [Final results after operative treatment of shoulder joint infections].
AB  - PURPOSE: In a consecutive case series the results of operative treatment of
      patients with shoulder joint infections following rotator cuff surgery,
      endoscopic subacromial decompression or subacromial injection were studied.
      PATIENTS AND METHODS: Between 1990 and 2001 26 patients developed a postoperative
      infection. 24 patients were available for a mean follow-up of 4.3 (1-12) years.
      The mean age of the study group was 59.8 (28-84) years. Patients were divided
      into three groups. Group I consisted of 9 patients with infection after rotator
      cuff repair, group II consisted of 4 patients with infection after endoscopic
      subacromial decompression and there were 11 patients in group III with an
      infection that developed following subacromial injection. Patient evaluation was
      done according to the Constant and ASES Scores, the SF-36 and a visual analogue
      scale (VAS) for postoperative pain and satisfaction. RESULTS: The mean
      postoperative Constant Score was 68.6 pts (SD 25.1) in group I, 84.6 pts (SD
      10.4) in group II and 75.6 pts (SD 25.1) in group III. The mean ASES-Score was
      65.6 pts (SD 30.0) in group I, 69.8 pts (23.6) in group II and 78.5 pts (SD 25.7)
      in group III. The SF-36 showed for the summarized physical scale 37.3 pts (SD
      12.6) in the first, 39.8 pts (SD 5.8) in the second and 37.7 pts (SD 12.4) in the
      third group and for the summarized psychometric scale 40.4 pts (SD 2.7) in the
      first, 44.3 pts. (SD 10.8) in the second and 45.7 pts. (SD 10.1) in the third
      group. For the VAS for pain, group I had 4.3, group II 4.0 and group III 2.5 pts
      Patient satisfaction showed similar results with 6.4 pts in the first, 6.5 pts in
      the second and 6.8 pts in the third group. CONCLUSION: Considering the functional
      results of operative revision, infection of the shoulder joint following rotator
      cuff surgery, endoscopic subacromial decompression or subacromial injection is a
      rare but severe complication.

PMID- 14679430
TI  - [Latissimus dorsi transfer in case of irreparable rotator cuff tear--a
      comparative analysis of primary and failed rotator cuff surgery, in dependence of
      deficiency grade and additional lesions].
AB  - AIM: Latissimus dorsi transfer is a difficult operation with a long
      rehabilitation. We investigated if it is worth the effort. METHOD: We used this
      technique in 22 patients with an inoperable rotator cuff tear (15 patients had a
      primary surgery, 7 patients were operated after failed prior rotator cuff
      repair). Additional lesions were also considered in the analysis. The average
      follow up was 9 months. The results were divided in 4 groups: severe indication,
      primary reconstruction, 3-tendon rupture, secondary reconstruction. RESULTS: The
      best results were achieved by the group "severe indication" (raising in the
      Constant score from 38 to 79 points). The group with primary surgery (increasing
      from 43 to 67 points) had better results than the group with failed prior
      reconstruction (increasing from 33 to 62 points). In case of additional rupture
      of the subscapularis tendon (45 to 58 points) or insufficiency of the deltoid
      muscle (33 to 45 points) the results are not satisfactory. The postoperative pain
      relief was felt as the predominant improvement. CONCLUSION: The latissimus dorsi
      transfer is a valuable and safely reproducible procedure. Depending on the
      preoperative grade of deficiency it is possible to achieve a shoulder function of
      60-90 % in comparison to the healthy shoulder. Despite the difficult operation
      technique and the long rehabilitation phase, the LDP is worth the effort on
      patients with irreparable rotator cuff tears. It is not the right procedure in
      cases of defect arthropathy--in these cases inverted shoulder prosthesis should
      be used.

PMID- 14679431
TI  - [Load shift-total hip replacement--numerical and clinical evaluation of a new
      concept of adaptive stem fixation].
AB  - AIM: The new load-shift fixation concept pursues the goal of an adaptive change
      of geometrical characteristics of the in-situ hip replacement. In this study a
      preclinical and clinical evaluation was performed. METHODS: By three-dimensional,
      dynamic finite element calculation the biomechanical properties of the prosthesis
      were analyzed in the early postoperative and long-term configuration. By clinical
      (20 +/- 10 months) and radiological (18 +/- 10 months) follow-up of a first
      series of implants (n = 20) the primary functional status of the prosthesis was
      examined in vivo. RESULTS: The preclinical results revealed that the metaphyseal
      micromotions are reduced significantly with the diaphyseal fit of the stem
      postoperatively. By absorption of a biodegradable element (spreader) integrated
      into the tip of the stem a change of stem geometry associated with loss of the
      diaphyseal fit occurs. This results in a complete shifting of load transmission
      into the metaphyseal area. In the clinical situation the postoperative Harris hip
      score averaged 92.9 +/- 10.5 points. Only in two patients did reversible episodes
      of thigh pain occur. The radiological analysis of bone remodeling phenomena
      pointed to a physiological load transmission. There was no evidence of loosening
      or osteolysis. On radiology, stem tapering could be demonstrated. CONCLUSION: On
      the basis of these promising preclinical and early clinical results the
      innovative load-shift prosthesis should now be further evaluated in prospective
      long-term studies.

PMID- 14679432
TI  - [Functional results following Girdlestone arthroplasty].
AB  - AIM: Aim of the investigation was to identify prognostic factors predicting the
      level of postoperative function following Girdlestone ("G")-arthroplasty.
      METHODS: Data were derived from 87 patients, 90 hips, treated with "G"
      arthroplasty at one institution between 1983 and 2000. RESULTS: Hip scores
      amounted to 38.7 (HHS) and 3.5 (Merle) points. The number of previously implanted
      total hip arthroplasties (THR) did not correlate with the functional result of
      "G"-arthroplasty (r = - 0.1400; p = 0.4524). On average, the duration of THR
      prior to "G"-arthroplasty was 44.6 months. Survival time of the latest THR and
      function of "G"-arthroplasty did not correlate (r = 0.0705; p = 0.7065). Patient
      age at primary THR, at follow-up, or at "G"-procedure did not correlate with HHS
      (r = - 0.0367, p = 0.8418, r = 0.1527, p = 0.4121; r = - 0.0151; p = 0.9356,
      respectively). Time following "G"-arthroplasty, averaging 90.6 months, did not
      correlate with patients function (r = 0.0920, p = 0.6289). Revision following "G"
      procedure and the presence of diabetes positively correlated (p = 0.0104). The
      appearance of cement in the femoral canal and radiographic signs of persistent
      bone infection correlated significantly (p = 0.0572). CONCLUSION: Patient age,
      duration of "G"-hips, and number of prior THR were not reliable to predict the
      function of "G"-arthroplasty.

PMID- 14679433
TI  - [Revision total hip arthroplasty: analysis of the predictive value of a
      radiographic classification system for assessment of bone stock loss].
AB  - AIM: The aim of this study was to evaluate the predictive value of a radiographic
      classification system concerning implant and bone graft in revision total hip
      arthroplasty. This classification is used to assess bone stock loss prior to
      surgery, thus hypothetically enabling an adequate choice of the implant and bone
      graft required. METHOD: 33 consecutive patients with the diagnosis of aseptic
      failure of total hip arthroplasty were included in the study. The investigation
      was performed using the classification system according to Saleh et al. The
      predictive value was analyzed by comparing the radiographically based
      recommendation concerning implant and bone graft and the intraoperative procedure
      according to a blinded observer technique. The Spearman coefficient of
      correlation (r (s)) was used to establish levels of agreement among multiple
      ordinal variables. RESULTS: Analysis of correlation between preoperative
      radiological estimations and intraoperative conclusions concerning implant and
      bone graft revealed coefficients of correlation (r (s)) of 0.53 (p < 0.01) for
      the acetabular and of 0.63 (p < 0.01) for the femoral classification. CONCLUSION:
      Our results indicate that the Saleh classification does not provide sufficient
      information for preoperative assessment of the revision implant and bone graft
      required concerning the acetabular side, whereas planning of the operative
      procedure regarding the femoral implant seems to be possible. These ambivalent
      findings should be taken into account prior to revision total hip arthroplasty.

PMID- 14679434
TI  - [Cemented versus cementless revision femoral stems using morselized allograft--a
      prospective, randomized study with 5 years follow-up].
AB  - BACKGROUND: There are only few studies on hip revision using the impaction
      grafting technique. Furthermore, data on cementless femoral stems as compared to
      cemented and polished femoral stems are lacking. We wanted to determine whether
      cementless femoral stems were equally good in preserving bone mineral density
      around the femoral stem and in functional outcome. METHOD: Consecutively 14
      patients needing hip revisions for aseptic loosening in the stem with bone stock
      deficiency Paparowsky grade II were randomized into two groups intraoperatively.
      Morselized fresh-frozen bone allografts were impacted in both groups. The
      cemented group received polished Landos Fjord-CrCo stems and the uncemented group
      received the hydroxyapatite-coated Landos Corail-Titan stems. The dual energy X
      ray absorptiometry was used to measure bone mineral density around the femoral
      stem according to Gruen zones. Function was measured by Merle d'Aubigne score.
      Patients were controlled at 0.5, 3, 6, 9, 12, 18, 24, 36 and 60 months
      postoperatively. RESULTS: There was no statistical difference between the BMD
      loss in the cemented vs. the uncemented group. The BMD loss was between 0-10 % in
      distal Gruen zones and was between 10-20 % in proximal Gruen zones. Functional
      scores were similar and reached a plateau of 16 in the Merle d'Aubigne score
      after 6 months. CONCLUSIONS: Cemented technique in hip revisions using morselized
      bone allograft is as good as uncemented technique in preserving BMD measured by
      the DEXA method and restoring function in a 5 years follow-up.

PMID- 14679435
TI  - [Midterm results after treatment of liposarcoma in the extremities].
AB  - PURPOSE: In this retrospective analysis, survival time, local recurrence and rate
      of metastasis were appraised in patients with primary liposarcoma of the
      extremities depending upon the applied primary and adjuvant therapy procedures.
      Furthermore, we compared the representativity of histological results of the
      biopsy with the final histology of the resected tumour. MATERIAL AND METHOD:
      Between 1990 and 1998, 27 patients were surgically treated who suffered from a
      primary liposarcoma of the extremities. At the mean follow-up time of 62.4 months
      (39-141 months) postoperative survival rate, rate of metastasis and local
      recurrence were determined. The results were analysed with regard to
      intraoperative resection distance, tumour size and localisation as well as
      histological classification of previous biopsy and finally resected tumour. The
      influence of radiotherapy on the results was also determined. RESULTS: In 5
      patients (18.5%) the amputation and in 22 cases (81.5%) the limb sparing
      resection of the liposarcoma was performed. 6 patients underwent a marginal
      resection and one patient an intralesional resection. At follow-up we observed a
      local recurrence rate of 22.2% (n = 6) and a survival rate of 74.1%. 18.5% of the
      patients had metastases. After adjuvant radiotherapy three patients (50%) showed
      local recurrence after marginal resection. In only 8 cases (29.6%) the results of
      primary biopsy and final tumour classification (entity, subtype and grading) were
      identical. CONCLUSION: The development of metastases (often pulmonary) and local
      recurrences even after long tumour-free interval makes adequate follow-up
      investigations mandatory in liposarcoma patients. With regard to the problems in
      assessing liposarcoma biopsies, MRI-orientated biopsies from several tumour areas
      via one biopsy approach are recommended.

PMID- 14679436
TI  - [Giant cell tumor of bone. An evaluation of 87 patients].
AB  - AIM: Giant cell tumor (GCT) of bone is a very peculiar and interesting tumor due
      to of its biological behavior and the phenomenon of pulmonary metastases of a
      histologically benign tumor. We present the results of a retrospective study.
      METHODS: Between 1965 and 2002 we treated 87 patients, 54 women and 33 men, for a
      GCT of bone. The average age of the patients was 28.2 (range 8-72) years. The
      median follow-up time was 91 months. 63 patients (72.4%) were hospitalized with a
      primary tumor. Twelve of these patients (19 %) had a pathological fracture. 24
      patients (27.6%) presented with local recurrence. 7 tumors were malignant GCT of
      bone, 80 tumors were benign. According to the classification of Campanacci, 9
      patients (10.3%) were diagnosed in stage I, 42 (48.3%) in stage II, and 36
      (41.4%) in stage III. Surgical procedures were intralesional curettage and
      packing with cement in 36 patients, and bone-grafting in 7. In 35 cases we
      performed a wide resection, and in nine an amputation. RESULTS: Local recurrence
      was observed in 11 patients (12.6%), all of them were benign GCT. Local
      recurrences were followed by an intralesional curettage and bone-grafting in
      three cases (42.8%), packing with cement in seven (19.4%). Three patients with
      local recurrence (27.3%) also had synchronous pulmonary metastases. All patients
      diagnosed with benign GCT are still alive. 3 out of 7 patients with malignant GCT
      died from progression of metastatic disease. CONCLUSION: To reduce the risk of
      local recurrence and pulmonary metastases, we recommend an adjuvant therapy of
      GCT.

PMID- 14679437
TI  - [Do organizational structures and factors influence the outcome of physiotherapy-
      a questionnaire survey related to whiplash-associated disorders].
AB  - BACKGROUND: The effectiveness of physiotherapy in patients with whiplash injuries
      of the cervical spine is a subject of critical discussion. Besides the inadequate
      situation with regard to the medical data available and the financial cuts in
      drug prescription, organizational factors and structures are assumed to be
      factors that have an influence on the effectiveness of physiotherapy. AIM: The
      aim of this study was to evaluate data on training, patient population,
      communication, prescription activity and therapies of physiotherapists. METHODS:
      In a survey of 213 physiotherapists in the City of Ulm, data were collected with
      the aid of questionnaires related to "therapy of whiplash-associated disorders".
      RESULTS: The results show deficits in the theoretical knowledge of
      physiotherapists, in the exchange of information and in therapy management. The
      survey further revealed that 22% of the patients decide themselves which therapy
      they will undergo. One can assume that these factors have a detrimental effect on
      the effectiveness of conservative therapy. CONCLUSION: An optimization of the
      organizational structures is thus urgently required and constitutes the only
      possibility, in the short to medium term, of improving the effectiveness of
      physiotherapy in patients with whiplash injuries of the cervical spine.

PMID- 14679438
TI  - [Improved osseointegration of titanium implants of different surface
      characteristics by the use of bone morphogenetic protein (BMP-3): an animal study
      performed at the metaphyseal bone bed in dogs].
AB  - AIM: Aim of this study was to determine whether coating of titanium implants of
      various surfaces with BMP-3 would improve the osseous integration of the implants
      into the orthotopic bony implant bed. METHOD: In this experimental study 190
      micro g per implant of highly purified bone morphogenetic protein 3 (BMP-3)
      precipitate isolated from porcine bone were available for the coating of each of
      24 cylindrical test implants (12 with hydroxyapatite and 12 with plasmapore
      surface). The remaining 24 test implants with the same surface makeup served as
      negative controls. Implantation sites were randomly assigned for the 4 versions
      of implants available and all implants were embedded into the medial or lateral
      femoral condyle of both legs of 12 German shepherds. The drilling holes were
      performed in such a matter that after embedding the cylindrical devices a gap of
      1 mm surrounding the implants remained. A biomechanical testing and histological
      evaluation was performed on the explants 42 days after surgery. RESULTS: In
      biomechanical testing forces necessary to extract the implants from the explanted
      bones in BMP-3 coated devices were up to 70% higher compared to the ones in the
      non-coated reference groups. Quantitative histomorphometric examination showed in
      BMP-3-coated implants an increasing formation of new bone close to their own
      surface (gap-healing) which was higher than in the corresponding non-coated
      controls (hydroxyapatite + BMP-3 32.1%, hydroxyapatite controls 20.3%, plasmapore
      + BMP-3 30.2%, plasmapore controls 13.1%). The extent of direct bone implant
      contact as percentiles of the corresponding implants perimeter (ongrowth) was
      also significantly higher in the BMP-3-coated implants compared to the non-coated
      controls (hydroxyapatite + BMP-3 37.7%, hydroxyapatite controls 22.4%, plasmapore
      + BMP-3 15.3%, plasmapore controls 6.4%). CONCLUSION: In this study it was proven
      the first time that implants of various surface textures as used in
      endoprosthetics are able to be coated by the osteoinductive growth factor BMP-3.
      In that way metallic implants can achieve osteogenic properties which have
      positive effects in osseointegration.

PMID- 14679439
TI  - [Mesenchymal stem cells for tissue engineering of bone: 3D-cultivation and
      osteogenic differentiation on mineralized collagen].
AB  - AIM: Due to their plasticity and high proliferation capacity in vitro, human
      mesenchymal stem cells (MSC) are promising candidates for substitution of
      mesenchymal tissues, such as bone. According to the tissue engineering concept,
      combinations of cells and three dimensional scaffolds are used to replace damaged
      tissue. Although various attempts have been made, the optimal combination of
      cells and artificial scaffold has not been found so far. METHODS: In this work,
      human MSC were isolated from bone marrow aspirates according to standard
      protocols and cultivated on mineralized collagen. Osteogenic differentiation was
      induced by medium containing dexamethasone, ascorbic acid and beta
      glycerophosphate. Cell proliferation on the scaffold (WST-1 vitality assay, total
      protein measurement) and osteogenic differentiation (quantitative Real-Time-RT
      PCR) were monitored for 24 days. RESULTS: Viable cells were found within the
      matrix throughout the cultivation period using histological and histochemical
      methods. Effective osteogenic differentiation could be demonstrated by the
      increase of expression of osteogenic marker genes (such as alkaline phosphatase)
      on a molecular level. CONCLUSION: Our results make the cell/matrix construct
      investigated in this work a promising candidate for tissue engineering of bone
      using mesenchymal stem cells. This has to be tested further by in vivo analysis.

PMID- 14679440
TI  - [Design and evaluation of the Extra Short Musculoskeletal Function Assessment
      Questionnaire XSMFA-D].
AB  - AIM: The XSMFA-D (German Extra Short Musculoskeletal Function Assessment
      Questionnaire) was developed on the basis of the SMFA-D to provide a short
      questionnaire for assessment of the functional status from patient's perspective
      in routine use. METHODS: Based on psychometric and medical aspects 16 items were
      extracted from the SMFA-D during an iterative process. 633 SMFA-D questionnaires
      of 199 patients were used as basic data. The XSMFA-D was evaluated on 67/51
      patients with primary osteoarthritis of the knee/hip undergoing total joint
      replacement. RESULTS: The tests for reliability and internal consistency produced
      favorable results. The Knee Score, Harris Hip Score, WOMAC and SMFA-D showed
      significant correlations to the XSMFA-D indicating construct validity. The
      criterion validity could be demonstrated successfully by relations with external
      parameters like walking distance, patients reported pain, mobility judgements by
      physicians and degree of osteoarthritis. The discriminant validity could also be
      demonstrated by significant differences between several different patient groups.
      Almost all effect sizes were generally large. CONCLUSIONS: The XSMFA-D could be
      demonstrated to be an appropriate short questionnaire for the evaluation of
      therapy results from patient's perspective. The use of the XSMFA-D can be
      recommended for routine use. Further investigations of the instrument will be
      undertaken.

PMID- 14679441
TI  - An Outbreak of Vibrio cholerae O1 infections on Ebeye Island, Republic of the
      Marshall Islands, associated with use of an adequately chlorinated water source.
AB  - In December 2000, physicians in the Republic of the Marshall Islands reported the
      first known outbreak of Vibrio cholerae O1 infection (biotype El Tor, serotype
      Ogawa) from this country. In a matched case-control study on Ebeye Island,
      patients with cholera (n=53) had greater odds than persons without cholera
      (n=104) to have drunk adequately chlorinated water collected from a US military
      installation on neighboring Kwajalein Island and transported back to Ebeye
      (matched odds ratio [MOR], 8.0; P=.01). Transporting or storing drinking water in
      a water cooler with a spout and a tight-fitting lid was associated with reduced
      odds of illness (MOR, 0.24; P<.01), as was drinking bottled water (MOR, 0.08;
      P<.01), boiled water (MOR, 0.47; P=.02), or water flavored with powdered drink
      mixes (MOR, 0.18; P<.01). No cases of cholera were reported among Kwajalein
      residents. This outbreak highlights the critical importance of handling and
      storing drinking water safely, especially during outbreaks of gastrointestinal
      illness.

PMID- 14679442
TI  - Relating the size of molecularly defined clusters of tuberculosis to the duration
      of symptoms.
AB  - Molecular profiling of Mycobacterium tuberculosis isolates has improved
      recognition of tuberculosis case clusters, but the determinants of cluster size
      are unknown. We hypothesized that longer duration of symptoms prior to initiation
      of tuberculosis therapy would be associated with increased cluster size. All
      patients with tuberculosis in Harris County, Texas, identified between 10/1/95
      and 12/31/97 through a prospective population-based project were interviewed, had
      their medical records reviewed, and had M. tuberculosis isolates molecularly
      characterized. There were 506 symptomatic, evaluable patients in 74 clusters,
      ranging in size from 2 patients (32 clusters) to 61 patients (1 cluster). The
      median duration of symptoms was 46 days (range, 1-471 days). There was no
      association between the log-transformed duration of symptoms and cluster size in
      univariate or multivariate analysis. In multivariate analysis, age and HIV
      coinfection were inversely related to cluster size, but only weakly. The size of
      molecularly defined clusters of tuberculosis was not related to the duration of
      symptoms of most patients who belonged to clusters.

PMID- 14679443
TI  - Treating foot infections in diabetic patients: a randomized, multicenter, open
      label trial of linezolid versus ampicillin-sulbactam/amoxicillin-clavulanate.
AB  - Foot infections in diabetic patients are predominantly caused by gram-positive
      cocci, many of which are now antibiotic resistant. Because linezolid is active
      against these pathogens, we compared the efficacy and safety of intravenous and
      oral formulations with that of intravenous ampicillin-sulbactam and intravenous
      and oral amoxicillin-clavulanate given for 7-28 days in a randomized, open-label,
      multicenter study of all types of foot infection in diabetic patients (ratio of
      linezolid to comparator drug recipients, 2:1). Among 371 patients, the clinical
      cure rates associated with linezolid and the comparators were statistically
      equivalent overall (81% vs. 71%, respectively) but were significantly higher for
      linezolid-treated patients with infected foot ulcers (81% vs. 68%; P=.018) and
      for patients without osteomyelitis (87% vs. 72%; P=.003). Cure rates were
      comparable for inpatients and outpatients and for both oral and intravenous
      formulations. Drug-related adverse events were significantly more common in the
      linezolid group, but they were generally mild and reversible. Linezolid was at
      least as effective as aminopenicillin/beta-lactamase inhibitors for treating foot
      infections in diabetic patients.

PMID- 14679444
TI  - A molecular epidemiological assessment of extrapulmonary tuberculosis in San
      Francisco.
AB  - The epidemiology of extrapulmonary tuberculosis (TB) is not well understood. We
      studied all cases of extrapulmonary TB reported in San Francisco during 1991-2000
      to determine risk factors for extrapulmonary TB and the proportion caused by
      recent infection. Isolates were analyzed by IS6110-based restriction fragment
      length polymorphisms analysis. There were 480 cases of extrapulmonary TB, of
      which 363 (76%) were culture positive; isolates were genotyped for 301 cases
      (83%). Multivariate analysis identified young age, female sex, and HIV infection
      as independent risk factors for nonrespiratory TB (excluding pulmonary, pleural,
      and disseminated TB). Pleural TB was less common in HIV-seropositive persons and
      women than were nonrespiratory forms of extrapulmonary TB. Pleural TB is
      different from other forms of extrapulmonary TB and is associated with the
      highest clustering rate (35% of cases) of all forms of TB. This high rate of
      clustering occurs because pleural TB is often an early manifestation of recent
      infection.

PMID- 14679445
TI  - Adjunctive granulocyte colony-stimulating factor for treatment of septic shock
      due to melioidosis.
AB  - Melioidosis, caused by the intracellular pathogen Burkholderia pseudomallei, is
      endemic in northern Australia and Southeast Asia. Risk factors for this infection
      have also been associated with functional neutrophil defects. Because of this,
      granulocyte colony-stimulating factor (G-CSF) was adopted for use in patients
      with septic shock due to melioidosis in December 1998. We compared the mortality
      rates from before and after the introduction of G-CSF therapy at the Royal Darwin
      Hospital (Darwin, Australia) during the period of 1989-2002. The mortality rate
      decreased from 95% to 10% after the introduction of G-CSF. Risk factors, the
      duration of illness before presentation, and the severity of illness were similar
      in both groups. A smaller decrease in mortality among patients in the intensive
      care unit who did not have melioidosis was observed, suggesting that other
      changes in management did not account for the magnitude of the benefit seen. We
      conclude that G-CSF may have contributed to the reduction in the mortality rate
      among patients with septic shock due to melioidosis.

PMID- 14679446
TI  - The clinical management and outcome of nail salon-acquired Mycobacterium
      fortuitum skin infection.
AB  - Nontuberculous mycobacterial infections are becoming more common. Recently,
      Mycobacterium fortuitum and other rapidly growing mycobacteria have been found to
      cause severe skin and soft-tissue infections in association with nail salon
      whirlpool footbaths. We recently investigated a large outbreak of M. fortuitum
      furunculosis among women who received pedicures at a single nail salon. To better
      define the clinical course of such infections, we collected clinical details from
      physicians who were treating outbreak patients. We constructed multivariable
      linear models to evaluate the effect of antibiotic treatment on disease duration.
      Sixty-one patients were included in the investigation. The mean disease duration
      was 170 days (range, 41-336 days). Forty-eight persons received antibiotic
      therapy for a median period of 4 months (range, 1-6 months), and 13 persons were
      untreated. Isolates were most susceptible to ciprofloxacin and minocycline. Early
      administration of therapy was associated with shorter duration of disease only in
      persons with multiple boils (P<.01). One untreated, healthy patient had lymphatic
      disease dissemination.

PMID- 14679447
TI  - Real-time blood plasma polymerase chain reaction for management of disseminated
      adenovirus infection.
AB  - We evaluated the usefulness of quantifying blood plasma adenovirus DNA loads for
      the management of adenovirus infection. Quantification of adenovirus A, B, and C
      DNA loads was done with real-time polymerase chain reaction (PCR) assays. Blood
      plasma specimens obtained from 44 immunocompromised patients were screened
      prospectively with this method. PCR findings for 36 patients were negative, and
      none of the patients developed disseminated adenoviral disease. PCR findings for
      8 patients were positive; all 8 had invasive adenoviral disease and were treated
      with cidofovir. Sequential measurements of adenovirus DNA loads were performed to
      monitor the effect of cidofovir therapy. Decrease in the blood plasma DNA load
      was significantly higher in patients with a good response to cidofovir than in
      patients with a poor response and was therefore correlated with survival.
      Detection of adenovirus DNA in blood plasma appears to be useful for identifying
      patients at risk for invasive disease. Moreover, quantification of adenovirus DNA
      loads in plasma is helpful for monitoring the efficacy of antiviral therapy.

PMID- 14679448
TI  - Clinical features and outcomes of bacteremia caused by Enterococcus casseliflavus
      and Enterococcus gallinarum: analysis of 56 cases.
AB  - The clinical significance and virulence potential of Enterococcus
      casseliflavus/flavescens and Enterococcus gallinarum are still uncertain. We
      retrospectively analyzed 56 cases of significant bacteremia caused by E.
      casseliflavus or E. gallinarum. Of these cases, 25 (44.6%) were associated with
      polymicrobial bacteremia, and 43 (76.8%) were associated with entry via the
      biliary tract. Resistance to vancomycin was observed in 17 (30.4%) of these 56
      patients, and this resistance was significantly associated with E. gallinarum
      bacteremia (adjusted odds ratio [AOR], 10.56; 95% confidence interval [CI], 2.41
      46.27) and bacteremia without biliary tract origin (AOR, 6.74; 95% CI, 1.44
      31.67). The crude mortality rate was 13%, and the bacteremia-related mortality
      rate was 1.9%. In conclusion, bacteremia due to E. casseliflavus and E.
      gallinarum is commonly associated with biliary tract disease and may be
      associated with a low risk of mortality.

PMID- 14679449
TI  - Lactobacillus bacteremia, clinical significance, and patient outcome, with
      special focus on probiotic L. rhamnosus GG.
AB  - Lactobacillus bacteremia is a rare entity, and its clinical significance is
      poorly defined. We have reviewed the risk factors and outcome for 89 case
      patients with Lactobacillus bacteremia. Species characterization was done in 53%
      of the cases, revealing 25 L. rhamnosus strains and 22 other Lactobacillus
      species. In 11 cases, the strain was identical with the probiotic L. rhamnosus
      GG. In 82% of the cases, the patients had severe or fatal comorbidities.
      Predisposing factors to bacteremia were immunosuppression, prior prolonged
      hospitalization, and prior surgical interventions. No significant differences
      were observed in these predisposing factors or clinical features between patients
      with cases associated with the various Lactobacillus species, other than higher C
      reactive protein values in patients with L. rhamnosus bacteremia. Mortality was
      26% at 1 month and was 48% at 1 year. In multivariate analysis, severe underlying
      diseases were a significant predictor for mortality (odds ratio [OR], 15.8),
      whereas treatment with antimicrobials effective in vitro was associated with
      lower mortality (OR, 0.22). We conclude that lactobacilli in blood cultures are
      of clinical significance and that their susceptibility should guide decisions
      about antimicrobial treatment.

PMID- 14679450
TI  - Emergence of echovirus type 13 as a prominent enterovirus.
AB  - In 2001, increased activity of the rarely detected enterovirus echovirus type 13
      (E13) was observed in the United States. This article describes the
      epidemiologic, clinical, and genetic characteristics of E13 activity in the
      United States in 2001, compared with E13 activity abroad in 2000-2002. In the
      United States, E13 accounted for 376 (24%) of the 1584 enterovirus isolates
      reported in 2001 (29% of the reported isolates had a known serotype), compared
      with 74 isolates reported during 1970-2000. Five states reported aseptic
      meningitis outbreaks associated with E13, for a total of 521 cases. All
      characterized E13 isolates from the United States, Europe, Asia, and Oceania
      recovered in 2000-2002 were at least 95% identical to each other in VP1 capsid
      gene sequence, but they were genetically distinct from E13 isolates recovered
      before 2000. Continued surveillance of enteroviruses is important to alert
      physicians and public health officials to changes in disease trends and to
      improve efficiencies of clinical intervention.

PMID- 14679451
TI  - Antimicrobial resistance trends and outbreak frequency in United States
      hospitals.
AB  - We assessed resistance rates and trends for important antimicrobial-resistant
      pathogens (oxacillin-resistant Staphylococcus aureus [ORSA], vancomycin-resistant
      Enterococcus species [VRE], ceftazidime-resistant Klebsiella species [K-ESBL],
      and ciprofloxacin-resistant Escherichia coli [QREC]), the frequency of outbreaks
      of infection with these resistant pathogens, and the measures taken to control
      resistance in a stratified national sample of 670 hospitals. Four hundred ninety
      four (74%) of 670 surveys were returned. Resistance rates were highest for ORSA
      (36%), followed by VRE (10%), QREC (6%), and K-ESBL (5%). Two-thirds of hospitals
      reported increasing ORSA rates, whereas only 4% reported decreasing rates, and
      24% reported ORSA outbreaks within the previous year. Most hospitals (87%)
      reported having implemented measures to rapidly detect resistance, but only
      approximately 50% reported having provided appropriate resources for
      antimicrobial resistance prevention (53%) or having implemented antimicrobial use
      guidelines (60%). The most common resistant pathogen in US hospitals is ORSA,
      which accounts for many recognized outbreaks and is increasing in frequency in
      most facilities. Current practices to prevent and control antimicrobial
      resistance are inadequate.

PMID- 14679452
TI  - Age distribution for T cell reactivity to vaccinia virus in a healthy population.
AB  - The potential for bioterrorism involving smallpox has led to a debate about the
      durability of protective immunity against smallpox from vaccination. By assessing
      the T cell reactivity to vaccinia virus in a healthy population, we show that
      subjects who were vaccinated within the past 3 decades and who have a visible
      vaccination scar had remarkable T cell reactivity. However, person who were
      vaccinated within the past 3 decades but who do not have a scar and those who
      were vaccinated >4 decades ago had responses as low as those in unvaccinated
      subjects. Thus, we estimate that the significant T cell memory response to
      vaccinia virus from successful vaccination may persist for only 20-30 years.
      Furthermore, we found the vaccinia-specific cellular immunity could be easily
      assessed by determination of the frequencies of vaccinia-specific CD69 expression
      on T cell subsets. These data may help in the development of public health
      strategies to counter bioterrorism threats associated with smallpox.

PMID- 14679453
TI  - New data in a 200-year investigation.

PMID- 14679454
TI  - Quinupristin-dalfopristin resistance in gram-positive bacteria: mechanism of
      resistance and epidemiology.
AB  - Antimicrobial resistance in gram-positive bacteria is a continuing problem
      resulting in significant morbidity, mortality, and cost. Because of this
      resistance, new antimicrobial agents have been needed. Quinupristin-dalfopristin
      is a recently approved agent for treatment of these infections. Shortly after its
      introduction into clinical medicine, resistance was reported. Resistance can
      occur by one or more of several mechanisms, including enzymatic modification,
      active transport of efflux mediated by an adenosine triphosphate-binding protein,
      and alteration of the target site. Resistance is rare in isolates of
      staphylococci and Enterococcus faecium from humans. Resistance is common in
      isolates recovered from food animals and is related to the use of virginiamicin
      as a feed additive. Considering the effect antimicrobial resistance has on human
      health, as well as its economic impact, measures to preserve the usefulness of
      these agents and delay the development of resistance are urgently needed.

PMID- 14679455
TI  - The clinical significance of macrolide-resistant Streptococcus pneumoniae: it's
      all relative.
AB  - Macrolides are currently recommended as first-line agents for the empirical
      treatment of community-acquired pneumonia. Heavy use of these agents for a
      variety of indications has resulted in an increasing incidence of macrolide
      resistance among pneumococcal isolates. Although several case reports and small
      case series have suggested that in vitro macrolide resistance is associated with
      treatment failure in cases of pneumococcal pneumonia, other observational data
      suggest that drug susceptibility testing may not correlate with treatment
      failure. In this article, we review current information on the mechanisms of
      macrolide resistance and the pharmacodynamics of macrolide therapy, together with
      efficacy data from animal models and clinical observations, to begin to gauge the
      clinical significance of macrolide resistance in Streptococcus pneumoniae. Areas
      for further investigation are highlighted.

PMID- 14679456
TI  - Recommendations for incorporating human immunodeficiency virus (HIV) prevention
      into the medical care of persons living with HIV.
AB  - The estimated number of annual new human immunodeficiency virus (HIV) infections
      in the United States has remained at 40,000 for >10 years. Reducing the rate of
      transmission will require new strategies, including emphasis on prevention of
      transmission by HIV-infected persons. Medical care providers can affect HIV
      transmission by screening HIV-infected patients for risk behaviors, communicating
      prevention messages, discussing sexual and drug-use behaviors, reinforcing
      changes to safer behavior, referring patients for services such as substance
      abuse treatment, facilitating partner counseling and referral, and identifying
      and treating other sexually transmitted diseases. The Centers for Disease Control
      and Prevention (CDC), the Health Resources and Services Administration (HRSA),
      the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA)
      of the Infectious Diseases Society of America (IDSA) have recently collaborated
      to develop evidence-based recommendations for incorporating HIV prevention into
      the medical care of persons living with HIV. This article summarizes key aspects
      of the recommendations.

PMID- 14679457
TI  - Risk behavior for transmission of human immunodeficiency virus (HIV) among HIV
      seropositive individuals in an urban setting.
AB  - We conducted interviews with 256 human immunodeficiency virus (HIV)-infected
      patients who attended an HIV clinic in New York City to assess ongoing risk
      behaviors for HIV transmission. After learning that the result of an HIV test was
      positive, 106 subjects (41%) had unprotected sex, 63 (25%) had a new sexually
      transmitted disease diagnosis, and 38 (15%) used injection drugs. Unprotected sex
      was reported by 50% of women, 29% of heterosexual men (P=.006, compared with
      women), and 42% of men who have sex with men, and it was reported more often by
      persons with a history of trading sex for money or drugs (P<.001). In
      multivariate analysis, unprotected sex was associated with a history of trading
      sex for money or drugs (adjusted odds ratio [AOR], 4.0; 95% confidence interval
      [CI], 2.2-7.0) and use of highly active antiretroviral therapy (AOR, 1.8; 95% CI,
      1.1-3.1). Ongoing risk-reduction counseling and substance abuse treatment for HIV
      infected persons are needed to reduce behaviors associated with HIV transmission.

PMID- 14679458
TI  - Incidence and predictors of severe liver fibrosis in human immunodeficiency virus
      infected patients with chronic hepatitis C: a European collaborative study.
AB  - A study was performed in 10 European health care centers in which 914 patients
      coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV)
      who had elevated serum alanine aminotransferase (ALT) levels underwent liver
      biopsy during the period of 1992 through 2002. Overall, the METAVIR liver
      fibrosis stage was F0 in 10% of patients, F1 in 33%, F2 in 22%, F3 in 22%, and F4
      in 13%. Predictors of severe liver fibrosis (METAVIR stage, F3 or F4) in
      multivariate analysis were age of >35 years (odds ratio [OR], 2.95; 95%
      confidence interval [CI], 2.08-4.18), alcohol consumption of >50 g/day (OR, 1.61;
      95% CI, 1.1-2.35), and CD4+ T cell count of <500 cells/mm3 (OR, 1.43; 95% CI,
      1.03-1.98). Forty-six percent of patients aged >40 years had severe liver
      fibrosis, compared with 15% of subjects aged <30 years. The use of antiretroviral
      therapy was not associated with the severity of liver fibrosis. In summary,
      severe liver fibrosis is frequently found in HCV-HIV-coinfected patients with
      elevated serum ALT levels, and its severity increases significantly with age. The
      rate of complications due to end-stage liver disease will inevitably increase in
      this population, for whom anti-HCV therapy should be considered a priority.

PMID- 14679459
TI  - Histoplasmosis and acquired immunodeficiency syndrome: a study of prognostic
      factors.
AB  - We aimed to identify prognostic factors for AIDS-associated disseminated
      histoplasmosis. In a multivariate analysis, we found that dyspnea, a platelet
      count of <100,000 platelets/mm3, and lactate dehydrogenase levels of >2 times the
      upper limit of the normal range were significantly independently associated with
      the death of the patient during the first 30 days of antifungal treatment.

PMID- 14679460
TI  - Fibrovascular changes misdiagnosed as cytomegalovirus retinitis reactivation in a
      patient with immune recovery.
AB  - A patient with human immunodeficiency virus infection and cytomegalovirus (CMV)
      retinitis developed immune recovery uveitis as a result of receipt of highly
      active antiretroviral therapy. Fibrovascular changes occurred in the CMV
      retinitis scar, were misdiagnosed as CMV retinitis reactivation, and were treated
      with anti-CMV medication. Fibrovascular membranes can be misdiagnosed as
      reactivated CMV retinitis, and a proper diagnosis is essential to avoid
      unnecessary therapy with potentially toxic antiviral medications.

PMID- 14679461
TI  - Outcome in patients with non-hodgkin lymphoma and with or without human
      immunodeficiency virus infection.
AB  - We compared the clinical characteristics and outcomes of 100 patients with human
      immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL; HIV-NHL)
      treated in the highly active antiretroviral therapy era with those of 82 HIV
      negative patients with aggressive NHL. The 3-year overall survival (OS) was 37%
      among patients with HIV-NHL and 74% among HIV-negative patients with NHL
      (P<.0001). However, the response-adjusted OS was similar in the 2 groups (hazard
      ratio, 1.4 for HIV-infected patients vs. 1 for HIV-negative patients; P=.24).
      Therefore, the achievement of complete remission should be the main goal in the
      treatment of patients with HIV-NHL.

PMID- 14679462
TI  - High prevalence of antibodies to Bartonella henselae among Italian children
      without evidence of cat scratch disease.
AB  - Few data are available on the seroprevalence of antibodies to Bartonella henselae
      among children. We retrospectively evaluated the presence of immunoglobulin G and
      M class antibodies to B. henselae in 508 children living in central Italy who
      were apparently free of any features suggesting B. henselae infection. We found
      that B. henselae infection is common among children in central Italy, occurs
      early in life, is in most cases asymptomatic, and resolves spontaneously.

PMID- 14679463
TI  - Clinical and microbiological characteristics of Rhizobium radiobacter infections.
AB  - Data obtained from 1996 to 2002 on 13 patients with Rhizobium radiobacter
      infections were analyzed. Ten patients (76%) had underlying hematological
      malignancy or solid-organ cancer. Six patients (46%) had febrile neutropenia
      during the course of R. radiobacter infection. The majority (54%) of infections
      were catheter-related bacteremia, and 92% of infections were hospital acquired.
      All the patients survived. Eighteen isolates were recovered from the 13 patients,
      and each isolate was susceptible to cefepime, piperacillin-tazobactam,
      carbapenems, and ciprofloxacin. The pulsed-field gel electrophoresis profiles
      differed among the isolates recovered from different patients, indicating the
      absence of nosocomial spread of the organism.

PMID- 14679464
TI  - Hypercalcemia: a manifestation of immune reconstitution complicating tuberculosis
      in an HIV-infected person.

PMID- 14679465
TI  - Use of veterinary vaccines associated with illness in a man.

PMID- 14679466
TI  - Delayed discovery of linezolid-resistant, vancomycin-resistant Enterococcus
      faecium: lessons learned.

PMID- 14679467
TI  - First report of Schistosoma mekongi infection with brain involvement.
AB  - We describe, to our knowledge, the first reported case of Schistosoma mekongi
      infection with brain involvement. S. mekongi is a distinct species most closely
      related to Schistosoma japonicum that is endemic in a defined area of the Mekong
      River in Laos and Cambodia and characteristically associated with hepatosplenic
      disease. The patient had an excellent response to praziquantel therapy but
      required repeated courses of corticosteroid therapy to suppress recrudescent
      neurological symptoms.

PMID- 14679468
TI  - Colistin for Klebsiella pneumoniae-associated sepsis.
AB  - Klebsiella pneumoniae that was resistant to all available antibiotics (minimum
      inhibitory concentration of imipenem, 32 microg/mL), including carbapenems, was
      isolated from blood samples obtained from a 48-year-old patient in the intensive
      care unit. The patient developed septic shock, which was successfully treated
      with colistin, the only antibiotic with activity against this multidrug-resistant
      strain.

PMID- 14679469
TI  - Autoantibodies to interferon-gamma in a patient with selective susceptibility to
      mycobacterial infection and organ-specific autoimmunity.
AB  - We evaluated a patient with disseminated Mycobacterium tuberculosis and
      Mycobacterium chelonae infection, of which he died. He also developed autoimmune
      (type I) diabetes and primary hypothyroidism. His serum contained a high titer of
      immunoglobulin G autoantibody to interferon-gamma (IFN-gamma) capable of blocking
      in vitro responses to this cytokine by peripheral blood mononuclear cells from
      normal donors. These results suggest that autoantibodies to IFN-gamma can induce
      susceptibility to disseminated mycobacterial infection, which may be refractory
      to chemotherapy.

PMID- 14679472
TI  - Epidemiology of tuberculosis.
AB  - In the United States, many people erroneously think that tuberculosis (TB) is a
      disease of the past--an illness that no longer constitutes a public health
      threat. In reality, TB is one of the leading global causes of morbidity and
      mortality. According to the World Health Organization, which compiles annual
      country profiles of reported TB cases using standardized case definitions, 2.4
      million cases were reported in 2001. However, because of underreporting, the
      number of new TB cases is estimated to be 8.3 million, including 1.8 million
      deaths. In the United States, after more than 3 decades of steady downward
      trends, an unprecedented resurgence of TB occurred between 1985 and 1992. This
      increase was associated with deficient infrastructure, the human immunodeficiency
      virus (HIV) epidemic, immigration, outbreaks in congregate settings, and
      widespread occurrence of multidrug resistant TB strains. The resultant increased
      concerns provided the impetus for the development of a national action plan to
      combat MDR and the mobilization of new resources. Consequently, the incidence of
      TB cases has decreased from 1992 through 2002. New challenges are evident and
      must be addressed to achieve the agreed-on goal of eliminating TB in the United
      States. This report describes the global epidemiology of TB and the epidemiology
      in the United States, and outlines future challenges to the elimination of TB in
      the United States.

PMID- 14679473
TI  - The diagnosis of tuberculosis: what's old, what's new.
AB  - The approach to the diagnosis of both active tuberculosis and latent infection
      has changed very little in the past several decades. For active disease, sputum
      smears with or without chest radiographs to aid in diagnostic accuracy, form the
      cornerstone of the diagnostic approach in many high-burden countries. These tests
      usually are supplemented by cultures when resources permit. The diagnosis of
      latent infection still relies on the use of the tuberculin skin test using
      purified protein derivative. The current global tuberculosis epidemic, which
      features large numbers of patients with human immunodeficiency virus infection
      and increasing rates of multidrug-resistant tuberculosis, makes accurate and
      rapid diagnosis of tuberculosis more urgent than ever before. Currently available
      technologies, most involving techniques of DNA amplification, can substantially
      improve the accuracy of the diagnosis of tuberculosis, although the use of such
      assays has been sharply limited because of concerns about cost. However, economic
      analyses suggest that these assays can be cost effective if they lead to sharp
      reductions in transmission through earlier treatment of infectious cases.

PMID- 14679474
TI  - Treatment of latent tuberculosis infection.
AB  - Treatment of latent tuberculosis infection (LTBI) is considered an essential
      component of TB control programs in several industrialized countries and is being
      used in selected situations in developing countries. In 2000, the American
      Thoracic Society (ATS) and Centers for Disease Control and Prevention (CDC)
      published new recommendations on the diagnosis and treatment of LTBI. These
      guidelines emphasized targeted tuberculin testing as a means of diagnosis in
      populations at risk, and expanded the choice of drug regimens to be used for
      treatment. After the implementation of the recommendations, unexpected and
      serious hepatic injury with the use of rifampin and pyrazinamide occurred,
      resulting in a modification of the recommendations. This article reviews the
      populations who should be considered for targeted tuberculin testing, scientific
      rationale for the selected treatment regimens, recently completed studies related
      to rifampin and pyrazinamide, and the prior and updated recommendations for
      treatment of LTBI.

PMID- 14679475
TI  - Clinical and radiographic features of HIV-related tuberculosis.
AB  - Human immunodeficiency virus (HIV)-related tuberculosis can be life-threatening
      for the individual, transmissible to others, and difficult to diagnose. We review
      the clinical, radiographic, and histopathologic features of HIV-related
      tuberculosis, and the ways in which these features are affected by the degree of
      immunodeficiency. At CD4 cell counts greater than 350 cells/microL, HIV-related
      tuberculosis has a similar presentation to tuberculosis in HIV-uninfected adults,
      predominantly pulmonary involvement with fibronodular and/or cavitary
      infiltrates. With progressive immunodeficiency, extrapulmonary involvement
      becomes increasingly common. Pulmonary involvement remains common at all stages
      of HIV disease, but the radiographic pattern is very different among persons with
      advanced immunodeficiency, in whom the most common abnormalities are
      intrathoracic adenopathy, focal lower or middle lobe infiltrates, and diffuse
      miliary or nodular infiltrates. The keys to the diagnosis of HIV-related
      tuberculosis are knowledge of the epidemiology of tuberculosis, recognition of
      the ways that immunodeficiency changes the clinical presentation, and an
      assiduous effort to obtain specimens for mycobacterial smear and culture.

PMID- 14679476
TI  - Pediatric tuberculosis.
AB  - Pediatric tuberculosis (TB) is different than that in adults in several ways. (1)
      The diagnosis of TB is more difficult in children due to non-specific or complete
      absence of symptoms and difficulty in confirming the diagnosis microbiologically.
      (2) Young children suffer more extrapulmonary and disseminated TB than adults.
      (3) Treatment of TB in children is challenging due to the lack of pediatric drug
      formulations and challenges in monitoring for toxicity. Fortunately, children
      generally do very well with treatment and tolerate the medications well.
      Treatment regimens are very similar to those used in adults. Four drug treatment
      should be initiated for treatment of presumed active TB if there are any risks of
      drug resistance in the child or adult source case (including residence or travel
      to an area where there is > 4% resistance to INH). (4) Children should be TB skin
      tested only if they have risks for TB infection, are likely to progress to active
      TB, or are suspected of having active TB. Unlike adults, all children should be
      treated for latent TB infection if identified because the therapy is very safe in
      young people, they were likely to have been infected relatively recently, and
      they have a long time to reactivate their latent infection. (5) Young children
      are not contagious with active TB and acquired their disease from shared airspace
      with adolescents or adults with pulmonary TB or ingestion of unpasturized milk
      products (M. bovis).

PMID- 14679477
TI  - Mycobacterium tuberculosis: the treatment of active disease.
AB  - Mycobacterium tuberculosis (MTB) remains a worldwide health care challenge
      despite the relatively recent evolution of effective antituberculous medications
      and combination drug therapy. In many parts of the world, the continued high
      prevalence of MTB disease is caused in part by the lack of availability of
      medications and the growing problem of multidrug-resistant TB (MDR-TB). In the
      United States, however, errors in treatment constitute a significant portion of
      treatment failures and relapses. The eradication of MTB in the United States is
      an achievable goal through the strict adherence to several treatment principles
      that have been developed over the latter half of the 20th century. These include
      (1) the use of multiple drugs to which the organism is sensitive; (2) using these
      drugs in appropriate combinations for a sufficient period of time; (3) using
      directly observed therapy whenever possible; (4) using in vitro drug
      susceptibility and local resistance patterns to guide initial drug choices; and
      (5) never adding a single drug to a failing regimen. Strict adherence to these
      principles along with an emphasis on completing the total number of doses for a
      particular regimen will help to ensure fewer relapses/failures, achieve higher
      cure rates, and help eradicate MTB disease in this country.

PMID- 14679478
TI  - Environmental infection control of tuberculosis.
AB  - Current infection control guidelines for tuberculosis focus first on
      administrative interventions to promptly identify and isolate a known or
      suspected infectious case. Environmental control measures come next, and finally
      personal respiratory protection is recommended as a final strategy to prevent
      transmission. However, both environmental controls and the use of personal
      respiratory protection are also focused on known or suspected cases, and certain
      high-risk procedures. There is little focus on general medical areas where
      unsuspected cases are believed to transmit their infection before they become
      suspected cases. This review makes the case for increased attention to such areas
      as general medical wards, clinics, and waiting areas. Administrative controls are
      needed to improve detection and to reduce the possibility of transmission to high
      risk groups. Improved air disinfection through general ventilation, filtration,
      and ultraviolet germicidal irradiation are needed as ways to address this
      overlooked source of transmission.

PMID- 14679479
TI  - TB vaccines at the turn of the century: insights into immunity to M. tuberculosis
      and modern approaches for prevention of an ancient disease.
AB  - Tuberculosis (TB) remains a leading cause of infectious disease mortality
      worldwide, accounting for nearly 2 million deaths annually. Despite the
      availability of effective anti-TB therapy, the world's case burden of TB
      continues to climb, in part owing to the concurrent acquired immune deficiency
      syndrome pandemic. The widespread use of the current TB vaccine, the bacille
      Calmette-Guerin strain of M. bovis (BCG), has failed to curtail the TB epidemic
      and therefore strategies for the eradication of TB have centered on aggressive
      case-finding and managed treatment, such as directly observed treatment short
      course (DOTS). Although DOTS continues to have a significant impact, the ability
      of DOTS to eradicate TB is limited. Therefore, TB eradication will require the
      development of an improved vaccine, which, in turn, will require application of
      state-of-the-art vaccine technology and of our knowledge of TB immunology and TB
      genomics to this problem. In this article, knowledge about the requisite
      components of protective immunity, modern vaccine strategies, and elements of
      clinical trials required to evaluate vaccine efficacy, as well as the status of
      current TB vaccine candidates, are reviewed.

PMID- 14679481
TI  - Transition programs in cystic fibrosis centers.

PMID- 14679482
TI  - Transition programs in cystic fibrosis centers: perceptions of team members.
AB  - We previously surveyed cystic fibrosis (CF) center directors and adult patients
      with CF to assess their perceptions regarding transition from a pediatric to an
      adult setting. An important finding in those studies was a lack of standard
      programs for transfer of young adults with CF from pediatric to adult care
      settings. Patients with CF typically receive care from clinics utilizing a
      multidisciplinary approach, suggesting that every member of the CF team can
      impact the transition process. Our purpose in this study was to gain an
      appreciation for various team members' perspectives on transition. An Internet
      survey was offered to all CF centers across the country to be completed by team
      members, excluding physicians. We received 291 completed surveys, nearly half
      completed by nurses, but our respondents included social workers, nutritionists,
      respiratory therapists, and a few team members with other training. Nearly half
      of the respondents work for both pediatric and adult teams. The majority of
      respondents (71.8%) reported that their adult patients receive care from an
      internist in a separate adult program, but nearly 20% reported that a
      pediatrician follows their adult patients. A minority thought that age (37.4% of
      respondents), marriage (16.2%), and pregnancy (27.1%) were criteria for transfer,
      though most (86.2%) suggested that patients should be transferred by age 21
      years. Criteria precluding transfer included patient/family resistance (45%),
      disease severity (34%), and developmental delay (31.3%). It was uncommon (11.4%)
      for an introduction to the concept of transition at the time of diagnosis. Over
      one-half of patients did not meet the adult team until time of transfer. Team
      members' perceptions of patients' concerns were similar to what we had previously
      measured in physicians, again far greater than what we have measured in patients
      themselves. In many ways, what we have measured here in team members reflects
      what we have reported by physicians, demonstrating slow development of standard
      transition programs and an overestimate of patients' concerns regarding
      transition. These differences may impede the successful transition of patients
      into an adult program. It is clear from this study that team members have an
      interest in and opinions on transition, and are likely play a vital role in the
      transition process. Standard programs of transition should be developed, and team
      members should be engaged in that process.

PMID- 14679483
TI  - Increasing adherence to cystic fibrosis treatment: a systematic review of
      behavioral techniques.
AB  - Cystic fibrosis is a fatal chronic illness that primarily affects the respiratory
      and pancreatic systems. Treatment includes daily medications, enzyme and vitamin
      supplements, a high-calorie diet, and airway clearance sessions (e.g., chest
      physiotherapy, exercise). Although this regimen is essential to longevity,
      families have difficulty adhering to the multiple treatment components. Adherence
      is especially problematic with diet, chest physiotherapy, and exercise. Studies
      utilizing behavioral techniques to increase adherence to cystic fibrosis
      treatment components have been conducted with varying results. In this paper, a
      critical review of these treatment studies and suggestions for future work are
      presented.

PMID- 14679484
TI  - Lung function in children with diabetes mellitus.
AB  - A cross-sectional study design was undertaken to assess pulmonary function in
      children with insulin-dependent diabetes mellitus (IDDM), and to establish if
      there is any relationship with diabetic factors and complications. Thirty-eight
      children (10 +/- 1.8 years) with IDDM and without clinical or radiological
      evidence of lung involvement, and 41 healthy age-matched reference subjects,
      underwent a pulmonary function study. Thirteen (34%) of 38 subjects with IDDM
      were studied at the onset of their disease. Adjusted values expressed as SD score
      of forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1)), and
      the transfer factor for carbon monoxide (TLCO) were found to be significantly
      lower than in controls (-0.54 +/- 0.87 vs. 0.40 +/- 1.10, P = 0.0008; -0.11 +/-
      0.96 vs. 0.52 +/- 1.07, P = 0.01; -1.60 +/- 1.07 vs. -0.57 +/- 1.28, P = 0.001,
      respectively). These differences also existed in the group investigated at onset
      of diabetes. Residual volume (RV) and RV/total lung capacity ratio (RV/TLC) were
      significantly higher in the whole group of patients with IDDM than in controls (
      0.20 +/- 0.83 vs. -0.80 +/- 0.88, P = 0.003; and 26 +/- 6.2 vs. 21 +/- 5.0, P =
      0.0002, respectively). Seventeen patients (45%) had abnormal pulmonary function
      (SD score, less than -1.64): 16 subjects had reduced TLCO, 4 had reduced FVC, and
      in 3 of the 17, both functional indices were abnormal. There was no significant
      relationship between pulmonary function indices and diabetic factors or
      complications. The only significant association was between abnormal TLCO and
      females (P = 0.03), suggesting that sex may be a predisposing factor for the
      development of pulmonary complications. This study supports the view that the
      lung is functionally involved in children with IDDM early on in the course of the
      disease.

PMID- 14679485
TI  - Measuring exhaled nitric oxide in infants during tidal breathing: methodological
      issues.
AB  - Exhaled nitric oxide (FENO) may provide a tool for identifying infants at risk of
      developing allergic disease in childhood. In infants there is no standardized
      collection technique; however, the easiest method is to measure FENO during tidal
      breathing. In this study we investigated various methodological issues for tidal
      breathing (TB) FENO in infants. These included the effect of ambient NO, oral or
      nasal breathing, sedation, and tidal expiratory flow. Furthermore, we compared TB
      FENO in 88 infants with and without wheeze. Ambient NO greater than 5 ppb
      significantly affected FENO. There was no significant difference between NO
      levels measured during either oral or nasal breathing; however, there was a
      significant difference between levels collected from infants before and after
      sedation (P < 0.001). Tidal breathing FENO decreased with increasing tidal flows
      (P < 0.001) and increased with age (P = 0.002). There was no significant
      difference in mixed expired NO between healthy and wheezy children, but children
      with doctor-diagnosed eczema had significantly raised levels (P = 0.014). There
      seem to be important methodological limitations for measuring FENO in infants
      during TB.

PMID- 14679486
TI  - Airway resistance by the interrupter technique: which algorithm for measuring
      pressure?
AB  - Airway resistance using the interrupter technique (Rint) can be measured using
      commercial devices which employ different algorithms for estimating pressure
      change. We aim to describe differences in Rint due to algorithm. We compared Rint
      and change in Rint after bronchodilator, using four algorithms to estimate
      pressure change following interruption: 1) two-point back-extrapolation to
      interruption from points 70 msec and 30 msec from interruption, and similarly 2)
      to 15 msec from interruption, 3) at two-thirds from interruption, and 4) near end
      interruption. Flow was measured immediately before interruption. Our subjects
      were 39 asymptomatic children 2-5 years old with previous intermittent wheeze.
      Rint differed significantly with algorithm. Geometric mean Rint (95% confidence
      interval (CI)) for algorithms 1-4 were 1.21 kPa x l(-1) x sec (1.18-1.24 kPa x l(
      1) x sec), 1.31 kPa x l(-1) x sec (1.28-1.34 kPa x l(-1) x sec), 1.57 kPa x l(-1)
      x sec (1.54-1.61 kPa x l(-1) x sec) and 1.71 kPa x l(-1) x sec (1.67-1.75 kPa x
      l(-1) x sec), respectively. Measurement of change in R(int) following
      bronchodilator (BDR) did not differ on average with algorithm. Geometric means
      (95% CI) for BDR measurements for algorithms 1-4 were 29.9% (26.0-34.0%), 30.4%
      (26.4-34.5%), 32.9% (28.8-37.1%), and 31.7% (27.6-35.8%), respectively. However,
      measurement of change in individuals could differ by up to 40%, depending on
      algorithm. In conclusion, there are significant differences in Rint, depending on
      algorithm used to estimate pressure change. Measurement of change in Rint is
      unaffected on average, although in individuals there could be significant
      differences. Each laboratory should state its method and use the same algorithm
      for longitudinal and group data.

PMID- 14679487
TI  - Can schoolchildren provide valid answers about their respiratory health
      experiences in questionnaires? Implications for epidemiological studies.
AB  - To evaluate the relative validity of information on children's respiratory
      experience given by different informants, we examined and compared the
      relationship between low ventilatory function (defined as more than 1 standard
      deviation below the corresponding mean) and schoolchildren's respiratory symptoms
      or illnesses reported separately by the children and their parents, using a
      standard respiratory questionnaire. A total of 1,963 children aged 8-12 years
      from 12 primary schools in three districts of Hong Kong provided parent-completed
      and self-completed questionnaires, as well as acceptable spirometric
      measurements. Prevalence of low forced expiratory volume ratio (FEV1/FVC) and low
      forced expiratory flow rate between 25-75% of FVC (FEF25-75) were higher among
      those with either parent or child-reported symptoms/illnesses. Child-reported
      cough and phlegm performed better than the corresponding parent-reported symptoms
      in predicting low FEV1/FVC. The contrary was true for wheezing and bronchitis.
      For low FEF25-75, parent-reported wheezing, asthma, and bronchitis performed
      better, while the opposite was true for cough. Subgroup analysis by age showed
      that for older children (age 10 or above), child-reported symptoms/illnesses
      performed better in general in the prediction of low FEV1/FVC. On the other hand,
      parent-reported symptoms/illnesses seemed to have an advantage over child
      reported ones in predicting low FEF25-75. Subgroup analysis by sex did not reveal
      any clear pattern. Overall, there was little difference between respiratory
      illness experiences reported by schoolchildren and their parents in terms of
      their associations with low ventilatory function. In a population-based study in
      which schoolchildren are subjects, it would be appropriate for respiratory
      questionnaires to be administered to the children themselves, especially if they
      have reached age 10. By doing so, higher response rates, and perhaps also better
      yields of correct information, may be obtained.

PMID- 14679488
TI  - Respiratory symptoms and lung function in relation to atopy in children born
      preterm.
AB  - Respiratory morbidity is a major health problem among children. The aim of this
      study was to compare the background of respiratory problems of children born
      preterm with that of children born full-term, with special reference to atopy.
      The study comprised two cohorts of 10-year-old children: a group of 72 children
      born preterm with birth weights of less than 1,501 g, and a group of 65 children
      born full-term with birth weights of over 2,500 g. Histories of respiratory and
      atopic symptoms, and of risk factors for atopy, were collected with a
      questionnaire. Predisposition to atopy was verified by skin-prick testing and by
      measuring serum total and antigen-specific IgEs. Lung function was evaluated by
      spirometry testing. Children born preterm had significantly more wheezing. In
      them, the lifetime prevalence of wheezing was 43%, vs. 17% in children born full
      term (P = 0.001; odds ratio, 3.71; 95% confidence interval, 1.67-8.25). In the
      full-term group, wheezing was associated with atopy: 64% of wheezers were atopic;
      in the preterm group, 23% of wheezers were atopic (difference between groups, P =
      0.024). Children born preterm expired significantly lower spirometry values of
      forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), FEV1/FVC
      ratio, forced expiratory flow after 50% of vital capacity has been exhaled
      (FEF50), and forced expiratory flow during middle half of FVC (FEF25-75). In the
      preterm group, wheezing, asthma, and low gestational age, but not atopy, were
      significantly associated with lower lung function values. Wheezers of the preterm
      group who still wheezed at age 10 were significantly more often atopic than those
      who no longer wheezed (62% vs. 9%, P = 0.006). In conclusion, we demonstrated a
      significant difference between groups in the association of atopy with
      respiratory problems. However, although atopy was not associated with a lifetime
      prevalence of respiratory symptoms in prematurely born children, an atopic
      predisposition in them was found to associate with persistence of wheezing.

PMID- 14679489
TI  - Lower airway obstruction, bronchial hyperresponsiveness, and primary pulmonary
      hypertension in children.
AB  - We investigated the prevalence and reversibility of lower airway obstruction
      (LAO) and its correlation with pulmonary artery pressure in children with primary
      pulmonary hypertension (PPH). The analysis was performed retrospectively in a
      cohort of children with PPH between 5-18 years of age. PPH was defined as mean
      pulmonary artery pressure (PAPm) >25 mmHg at rest, or >30 mmHg during exercise,
      with normal pulmonary capillary wedge pressure in the absence of other causes.
      Lower airway function was assessed by spirometry and maximal expiratory flow
      volume curves. Lung volumes were measured by body plethysmography. Patients were
      assigned according to their pattern of lung function into "normal,"
      "obstructive," and "restrictive" groups. The reversibility of LAO was defined as
      an increase of > or = 15% from baseline in forced expiratory volume at 1 sec
      (FEV1) and/or > or =20% in forced expiratory flow at 25-75% of forced vital
      capacity (FEF25-75%) in response to nebulized albuterol. An "obstructive" pattern
      was found in 23 children (59%), a "restrictive" pattern in 2 children (5%), and a
      "normal" pattern in 14 children (36%). Response to bronchodilator was documented
      in 78% of children with an "obstructive" pattern and in 22% of those with a
      "normal" pattern. The PAPm showed a significant positive correlation with the
      TLC, RV, and RV/TLC, but a negative one with the ratio FEV1/FVC. Our findings
      suggest that reversible LAO is the most common lung function abnormality among
      pediatric patients with PPH. Whether airway reactivity is a cause of or the
      result of PPH remains to be determined.

PMID- 14679490
TI  - Preserved diffusion capacity in children with cystic fibrosis.
AB  - Early detection of progressive lung disease in cystic fibrosis (CF) may lead to
      better treatment and prognosis. Routine lung function indices may be relatively
      insensitive markers of peripheral airway obstruction and alveolar collapse. We
      hypothesized that the single-breath diffusion capacity of the lung for carbon
      monoxide (DLCO) would change before tests of airway function in patients with CF.
      We assessed lung function longitudinally in 53 children with CF during a mean
      period of 3.8 years to determine whether the diffusion capacity of the lung
      becomes abnormal before more conventional indices of lung function do. Within
      patients, DLCO was slightly elevated and remained stable, while forced expired
      volume in 1 sec (FEV1) and forced vital capacity (FVC) declined progressively
      (mean individual decline, -1.8% and -0.8% of predicted). Cross-sectionally, this
      decline was faster (mean group decline -3.8% and -2.8% of predicted), indicating
      an additional cohort effect. Normalized diffusion capacity at an early stage of
      CF is slightly elevated and is preserved in spite of progressive obstructive lung
      disease. This can be attributed to alterations in pulmonary and bronchial
      circulation due to loss of function and/or number of alveolar units. Diffusion
      capacity at rest does not appear to be a suitable early marker of progressive
      deterioration of CF lung disease.

PMID- 14679491
TI  - Hering-Breuer reflex and sleep state in the preterm infant.
AB  - The aim of this study was to determine the effect of sleep state on the Hering
      Breuer inflation reflex in the preterm infant. Seventeen nonintubated, premature
      infants, ranging in birth weight from 980-2,440 g with postconceptual ages of 30
      36 weeks, were studied. In each infant, pulmonary function testing, including the
      Hering-Breuer inflation reflex, was obtained using the SensorMedics 2600 during
      active and quiet sleep states in supine position. The strength of the Hering
      Breuer inflation reflex was quantified by the measurement of the percent
      prolongation of expiration after an occluded breath. Sleep states were
      categorized by the criteria of Prechtl. There was a significant difference in
      Hering-Breuer activity in active (REM) vs. quiet (non-REM) sleep, with a
      consistently stronger reflex in the active sleep state. The mean percent
      prolongation of expiration was 419% in active sleep vs. 87% in quiet sleep.
      Analysis of the data, using a paired t-test, revealed a mean difference of 331 +/
      185% between active and quiet sleep (P = 0.000). In conclusion, significant
      differences in the strength of the Hering-Breuer inflation reflex occur in
      relation to sleep state, and may explain the variability of the reflex described
      in previous studies. Measurement of the Hering-Breuer inflation reflex may be
      affected by pulmonary stretch receptors as well as chest wall afferents in the
      preterm infant.

PMID- 14679492
TI  - Variation of peak inspiratory flow through dry powder inhalers in children with
      stable and unstable asthma.
AB  - Drug release from dry powder inhalers depends for a large part on a sufficiently
      high peak inspiratory flow (PIF). We determined the variation of PIF through two
      commonly prescribed dry powder inhalers in children with asthma. We analyzed the
      effect of inhaler device, age, and severity of asthma symptoms on variation of
      PIF. Fifty-eight children with asthma (4-15 years old) recorded PIF values
      together with asthma symptoms in a diary twice daily for 4 weeks. PIF was
      measured with a portable PIF-meter (In-Check) equipped with adapters to simulate
      flow resistance through the Accuhaler and Turbohaler inhalers. Children generated
      higher PIF values through an Accuhaler adapter than through a Turbohaler adapter
      (95% CI for difference, 25.7-31.7). Mean PIF values increased with age,
      independent of type of inhaler. The mean (SD) variation of PIF (low%high) was
      72.3 (8.1)% for patients using the Accuhaler adapter, and 67.0 (14.5)% for
      patients using the Turbohaler adapter (mean difference, 5.2%; 95% CI, -0.9 to
      11.4). Children < or =7 years of age had a significantly greater variation of PIF
      in addition to a lower mean PIF (P = 0.0003). PIF decreased significantly when
      symptoms of asthma increased (mean maximal decrease 11 l/min; P < 0.01), but the
      correlation between PIF and morning and evening symptoms was weak (r = -0.18 and
      r = -0.16, respectively). Patients who reported moderate or severe symptoms
      during the study period had a significantly greater variation of PIF compared to
      patients who remained free of symptoms or reported mild symptoms. The majority of
      patients generated PIF >30 l/min during the study, even when they experienced
      symptoms of asthma. The variation of PIF through the Accuhaler and Turbohaler
      adapter was significantly greater for children < or =7 years of age and for
      patients experiencing moderate or severe symptoms of asthma.

PMID- 14679493
TI  - Comparison of active cycle of breathing and high-frequency oscillation jacket in
      children with cystic fibrosis.
AB  - High-frequency chest compressions (HFCC) have been suggested as an alternative to
      conventional chest physiotherapy to aid sputum clearance in patients with cystic
      fibrosis (CF). We aimed to compare the active cycle of breathing techniques
      (ACBT) with the Hayek Oscillator Cuirass, performing HFCC on secretion clearance
      in children with CF during an exacerbation. Ten children (7 males; median age, 14
      years; range, 9-16) received either two supervised sessions using HFCC or two
      self-treatment ACBT sessions in random order on successive days. Baseline
      pulmonary function was similar prior to treatments. Sputum weight increased
      significantly with ACBT compared with HFCC during treatment (5.2 g vs. 1.1 g, P <
      0.005, morning; 4.1 g vs. 0.7 g, P < 0.01, afternoon). Pulmonary function
      improved significantly after morning ACBT (forced vital capacity (FVC): 2.67 l to
      2.76 l, P < 0.03; forced expiratory volume in 1 sec (FEV1): 1.59 l to 1.62 l, P <
      0.03). Following afternoon ACBT, there was a significant increase in FVC (2.64 to
      2.79, P < 0.02), but no significant change in FEV1. Pulmonary function did not
      change at any time following HFCC. Compared with ACBT, HFCC by Hayek Cuirass is
      not an effective airway clearance treatment modality for children with CF during
      an infective exacerbation.

PMID- 14679494
TI  - Sleep desaturation: comparison of two oximeters.
AB  - Oxygen saturation is measured by pulse oximetry during sleep studies. Body
      movements and peripheral vasoconstriction related to respiratory events may
      interfere with measurements by conventional oximeters. Our objective was to
      compare the detection rate of sleep desaturations by two oximeters, one of which
      used new motion-resistant technology. We studied 34 children (median age, 13
      years; range, 3-18) with suspected sleep-disordered breathing. During
      polysomnography, oxygen saturation was measured by two oximeters set on fast
      mode: the motion-resistant Radical oximeter (2-sec averaging), and the
      conventional Nellcor N-200 oximeter (2-3-sec averaging). Respiratory events were
      identified based on airflow signal. The numbers of respiratory event-related
      desaturations > or =3% or > or =5% detected by each oximeter were determined.
      Valid desaturations were defined using the Nellcor plethysmographic waveform and
      the Radical signal-quality data. Hypoxemic respiratory events were those with
      associated valid desaturation. In total, 1,278 respiratory events were identified
      and pooled. Basal oxygen saturation measured just before event onset was not
      different between oximeters (Radical: 98%; range, 84-100; Nellcor: 97%; range, 86
      100; P = ns). However, the Radical detected a greater number of valid
      desaturations than did the Nellcor for any level of desaturation (respectively, N
      = 651 and 476 desaturations > or =3%, P < 0.001; and N = 232 and 146
      desaturations > or =5%, P = 0.01). Consequently, for each patient, the number of
      hypoxemic respiratory events per hour of sleep was greater using the Radical than
      using the Nellcor (P = 0.002, and P = 0.021, for desaturation > or =3% and > or
      =5%, respectively). In conclusion, standardized oximeter settings are required to
      achieve more accurate assessments of hypoxemia in children with sleep-disordered
      breathing.

PMID- 14679495
TI  - Mucoepidermoid carcinoma of the bronchus presenting with a negative chest X-ray
      and normal pulmonary function in two teenagers: two case reports and review of
      the literature.
AB  - Two adolescents presented with a history of dyspnea upon exertion and cough. In
      both cases, the chest X-ray and pulmonary function testing, including flow-volume
      loop, were normal. A bronchial tumor was diagnosed by CT scan, which was ordered
      after each patient had an episode of hemoptysis. The sedimentation rate was the
      only abnormal laboratory test in both cases. Mucoepidermoid carcinoma of the
      bronchus, a rare tumor in childhood, was found at pathology in both cases. There
      was no evidence of metastases to local lymph nodes or distal sites. There were 47
      previously reported cases in children. Recurrent pneumonia and persistent cough
      were the most common presenting findings. These tumors are of low-grade malignant
      potential but they can become locally invasive, extending into cartilage and
      surrounding soft tissue. Prognosis is good with complete resection.

PMID- 14679496
TI  - 13C NMR and cerebral biochemistry.

PMID- 14679497
TI  - Reflections on the application of 13C-MRS to research on brain metabolism.
AB  - The power of (13)C-MRS lies in its unique chemical specificity, enabling
      detection and quantification of metabolic intermediates which would not be so
      readily monitored using conventional radiochemical techniques. Examples from
      animal studies, by examination of tissue extracts from the whole brain, brain
      slices and cultured cells, include observation of intermediates such as citrate
      and triose phosphates which have yielded novel information on neuronal/glial
      relationships. The use of (13)C-labelled acetate as a specific precursor for
      glial metabolism provided evidence in support of the view that some of the GABA
      produced in the brain is derived from glial glutamine. Such studies have also
      provided direct evidence on the contribution of anaplerotic pathways to
      intermediary metabolism. Analogous studies are now being performed on the human
      brain, where (13)C-acetate is used to quantitate the overall contribution of
      glial cells to intermediary metabolism, and use of (13)C-glucose enables direct
      calculation of rates of flux through the TCA (F(TCA)) and of the glutamate
      glutamine cycle (F(CYC)), leading to the conclusion that the rate of glial
      recycling of glutamate accounts for some 50% of F(TCA). The rate of 0.74 micromol
      min(-1) g(-1) for F(TCA) is compatible with PET rates of CMRglc of 0.3-0.4
      micromol min(-1) g(-1) (since each glucose molecule yields two molecules of
      pyruvate entering the TCA). Our brain activation studies showed a 60% increase in
      F(TCA), which is very similar to the increases in CBF and in CMRglc observed in
      PET activation studies.

PMID- 14679499
TI  - In vivo 1H-[13C]-NMR spectroscopy of cerebral metabolism.
AB  - 13C NMR spectroscopy in combination with the infusion of (13)C-labeled precursors
      is currently the only technique that is capable of quantitatively studying energy
      metabolism, neurotransmission and other metabolic pathways non-invasively in
      vivo. (1)H-[(13)C]-NMR spectroscopy is a high-sensitivity alternative to direct
      (13)C NMR spectroscopy. The development of improved NMR methods for water
      suppression, spatial localization, broadband decoupling, shimming and signal
      quantification, together with the availability of high magnetic field strengths,
      has made (1)H-[(13)C]-NMR spectroscopy the method of choice for the detection of
      metabolism at a high spatial and/or temporal resolution. (1)H-[(13)C]-NMR
      spectroscopy can now be used to discriminate glutamatergic (excitatory) and
      GABAergic (inhibitory) neuronal activity. The improved sensitivity allows the
      detection of metabolism in different tissues (e.g. gray and white matter) and
      potentially even in smaller structures, like cortical layers. Finally, (1)H
      [(13)C]-NMR spectroscopy allows the detection of energy metabolism and
      neurotransmission during functional activation, thereby further strengthening our
      understanding of the neurochemical basis of brain function.

PMID- 14679500
TI  - Clinical experience with 13C MRS in vivo.
AB  - 13C MRS was installed on a clinical scanner at 1.5 T in order to facilitate
      integrated MR examinations of human brain disorders. Using a simplified protocol,
      (1-(13)C) glucose and/or (1-(13)C) acetate were administered orally or by
      intravenous infusion. (13)C spectra of diagnostic quality were acquired in more
      than 100 consecutive studies. Novel (13)C neurochemical data contributed to the
      understanding of Alzheimer's, Canavan's, mitochondrial and hepatic
      encephalopathy, epilepsy and normal brain development. (13)C MRS uncovered
      hitherto unknown disorders of NAA-synthesis, glutamate neurotransmission, TCA
      cycle and glycolysis. Despite low inherent signal-to-noise, natural abundance
      (13)C MRS showed diagnostic promise. (13)C MRS is feasible in a clinical setting,
      at reasonable cost in neonates, children, adults and elderly patients.

PMID- 14679501
TI  - Regulation of glial metabolism studied by 13C-NMR.
AB  - Glial metabolism and their metabolic trafficking with neurons are essential parts
      of neuronal function, as they modulate, by this means, neuronal activity. Ex vivo
      and in vitro (13)C-NMR spectroscopy have been used to monitor neural cellular and
      tissue metabolism. Special emphasis has been given to the metabolic
      specialization of astrocytes and its enzymatic regulation. For this purpose
      primary cell cultures are useful tools to study neuronal-glial metabolic
      relationships as the extracellular fluid can be investigated and manipulated by
      various stimuli. In astrocytes, glucose is utilized predominantly anaerobically.
      Glycolysis is interrelated to the astrocytic TCA cycle via bi-directional signals
      and metabolic exchange processes between astrocytes and neurons. Besides glucose
      oxidation, neuronally released glutamate is metabolized through the glial TCA
      cycle. The flexibility of glutamate metabolism, depending on ammonia and energy
      homeostasis, and the discovered pyruvate recycling pathway in astrocytes,
      modulates the glutamine-glutamate cycle. (13)C-NMR studies have extended the
      concept of the "non-stoichiometric" glutamate-glutamine cycle between neurons and
      astrocytes. An alanine-lactate shuttle between neurons and astrocytes contributes
      to nitrogen transfer from neurons to astrocytes, recycles energy substrates for
      neurons, and in return promotes intercellular glutamine-glutamate cycling. The
      conversion of alanine to lactate in astrocytes is regulated by intracytosolic
      pyruvate compartmentation. In essence, the metabolic flexibility and
      compartmentalized enzymatic specialization of astrocytes buffers the brain tissue
      against metabolic impairments and excitotoxicity in response to extracellular
      stimuli, some of them being released by neurons. These in vitro studies using
      (13)C-NMR spectroscopy provide important knowledge regarding physiological and
      pathophysiological regulation of neural metabolism to improve our understanding
      of general brain function.

PMID- 14679502
TI  - Toward dynamic isotopomer analysis in the rat brain in vivo: automatic
      quantitation of 13C NMR spectra using LCModel.
AB  - The LCModel method was adapted to analyze localized in vivo (13)C NMR spectra
      obtained from the rat brain in vivo at 9.4 T. Prior knowledge of chemical-shifts,
      J-coupling constants and J-evolution was included in the analysis. Up to 50
      different isotopomer signals corresponding to 10 metabolites were quantified
      simultaneously in 400 microl volumes in the rat brain in vivo during infusion of
      [1,6-(13)C(2)]glucose. The analysis remained accurate even at low signal-to-noise
      ratio of the order of 3:1. The relative distribution of isotopomers in glutamate,
      glutamine and aspartate determined in vivo in 22 min was in excellent agreement
      with that measured in brain extracts. Quantitation of time series of (13)C
      spectra yielded time courses of total (13)C label incorporation into up to 16
      carbon positions, as well as time courses of individual isotopomer signals, with
      a temporal resolution as low as 5 min (dynamic isotopomer analysis). The
      possibility of measuring in vivo a wealth of information that was hitherto
      accessible only in extracts is likely to expand the scope of metabolic studies in
      the intact brain.

PMID- 14679498
TI  - Localized in vivo 13C NMR spectroscopy of the brain.
AB  - Localized (13)C NMR spectroscopy provides a new investigative tool for studying
      cerebral metabolism. The application of (13)C NMR spectroscopy to living intact
      humans and animals presents the investigator with a number of unique challenges.
      This review provides in the first part a tutorial insight into the ingredients
      required for achieving a successful implementation of localized (13)C NMR
      spectroscopy. The difficulties in establishing (13)C NMR are the need for
      decoupling of the one-bond (13)C-(1)H heteronuclear J coupling, the large
      chemical shift range, the low sensitivity and the need for localization of the
      signals. The methodological consequences of these technical problems are
      discussed, particularly with respect to (a) RF front-end considerations, (b)
      localization methods, (c) the low sensitivity, and (d) quantification methods.
      Lastly, some achievements of in vivo localized (13)C NMR spectroscopy of the
      brain are reviewed, such as: (a) the measurement of brain glutamine synthesis and
      the feasibility of quantifying glutamatergic action in the brain; (b) the
      demonstration of significant anaplerotic fluxes in the brain; (c) the
      demonstration of a highly regulated malate-aspartate shuttle in brain energy
      metabolism and isotope flux; (d) quantification of neuronal and glial energy
      metabolism; and (e) brain glycogen metabolism in hypoglycemia in rats and humans.
      We conclude that the unique and novel insights provided by (13)C NMR spectroscopy
      have opened many new research areas that are likely to improve the understanding
      of brain carbohydrate metabolism in health and disease.

PMID- 14679503
TI  - Feeding versus infusion: a novel approach to study the NAA metabolism in rat
      brain.
AB  - Using in vivo (13)C-NMR spectroscopy, the energy metabolism in rat brain has
      commonly been studied via infusion of (13)C-labeled substrates on a minute to
      hour time scale. In the present study, as a novel approach, (13)C-enriched animal
      chow was administered over several days and compared with a 2 h infusion of [U
      (13)C(6)]-glucose. Rats received chow containing either [U-(13)C(6)]-glucose or
      [U-(13)C]-biomass (a mixture of proteins, lipids, DNA, and carbohydrates) during
      3 to 5 days. During feeding with (13)C-labeled glucose and biomass, in vivo (13)C
      NMR spectroscopy was carried out daily and revealed slow but successive label
      incorporation into a large number of metabolites. Lipids and proteins were not
      significantly (13)C-enriched during a 2 h infusion of (13)C-labeled glucose, but
      became the most prominent resonances in the (13)C feeding experiment. Likewise,
      feeding with (13)C-enriched biomass led to additional (13)C-label incorporation
      into creatine, urea carbons and glycogen. Finally, only the acetyl moiety of N
      acetyl-aspartate (NAA) became significantly enriched during the 2 h infusion
      experiment, whereas the aspartyl moiety remained at natural abundance levels. In
      the feeding experiments, however, label incorporation into all carbons of NAA
      could be observed. Moreover, isotopomer analysis of brain extracts revealed that
      the acetyl moiety of NAA in feeding experiments was always more strongly (13)C
      enriched than its aspartyl moiety, suggesting that the turnover of the acetyl
      moiety is faster than that of the aspartyl moiety. The different enrichment
      kinetics of acetyl and aspartyl moiety could be explained by the existence of two
      different metabolic pathways reflecting the compartmentalised synthesis of NAA.

PMID- 14679504
TI  - Neuronal glial interaction in different neurological diseases studied by ex vivo
      13C NMR spectroscopy.
AB  - Nuclear magnetic resonance spectroscopy (NMRS) has been used extensively for
      several decades to elucidate metabolic pathways in biological systems and has led
      to new insights into cerebral metabolism. Many of these insights have been gained
      by NMRS using in vitro models, such as tissue extracts, cell cultures or brain
      slices. Extracts of cells or tissue provide an excellent basis for metabolic
      studies and facilitate the interpretation of in vivo spectra. (13)C NMRS is at
      present mostly used for in vitro or animal studies. Conclusions from the epilepsy
      models presented in this review are that turnover of metabolites is time
      dependent in kainate-injected rats with limbic seizures. Early and only
      temporarily enhanced astrocytic activity is followed by altered metabolism in
      neurons with an increased turnover of important amino acids such as GABA and
      glutamate. However, pentylenetetrazole (PTZ) kindling affects astrocytes in
      younger and glutamatergic neurons in older animals. In the presence of PTZ,
      phenobarbital decreases labeling of most metabolites in all cell types, except
      GABAergic neurons, from both labeled precursors in the younger animals. However,
      in older animals only GABAergic neurons are affected by phenobarbital, as
      indicated by an increase in GABA labeling. In kaolin-induced hydrocephalus it was
      shown that astrocyte metabolism is disturbed in the early phase, particularly in
      the cerebrum. These alterations continue into the chronic period. Only then do
      the first signs of neuronal metabolic impairment appear, which might explain why
      dementia is a prominent clinical feature in patients with chronic hydrocephalus.

PMID- 14679505
TI  - Involvement of brain lactate in neuronal metabolism.
AB  - The involvement of brain lactate in neuronal metabolism was analyzed by ex vivo
      NMR spectroscopy with rats under the effects of pentobarbital, alphachloralose or
      morphine, which were infused with a solution of either [1-(13)C]glucose+lactate
      or glucose+[3-(13)C]lactate for 20 min. Electroencephalogram recordings indicated
      different brain electrical activity levels under the three drugs with a clear
      distinction between pentobarbital, on the one hand, and alphachloralose and
      morphine on the other. Labeling of metabolites in brain perchloric acid extracts
      and of blood glucose and lactate was determined by (13)C- and/or (1)H
      observed/(13)C-edited-NMR spectroscopy. The following were found: (i) the ratio
      between glutamate C3 and C4 (13)C-enrichments increased from pentobarbital to
      alphachloralose and morphine whatever the labeled precursor, indicating a link
      between metabolic and electrical activity; (ii) under glucose+[3-(13)C]lactate
      infusion, alanine C3 and acetyl-CoA C2 enrichments were higher than that of
      lactate C3, revealing the occurrence of an isotopic dilution of the brain
      exogenous lactate (arising from blood) by lactate from brain (endogenous
      lactate); the latter was synthesized from glycolysis in a compartment other than
      the neurons; (iii) the contributions of labeled glucose and lactate to acetyl-CoA
      C2 enrichment indicated that the involvement of blood glucose relative to that of
      blood lactate to brain metabolism was correlated with brain activity. It can
      therefore be concluded that the brain electrical activity-dependent increase in
      the contribution of blood glucose relative to that of blood lactate to brain
      metabolism occurred partly via the increase in the metabolism of lactate
      generated from astrocytic glycolysis. This conclusion supports the hypothesis of
      an astrocyte-neuron lactate shuttle component in the coupling mechanism between
      cerebral activity and energy metabolism.

PMID- 14679506
TI  - Role of glial metabolism in diabetic encephalopathy as detected by high
      resolution 13C NMR.
AB  - The roles of glial energetics and of the glutamine cycle in diabetic
      encephalopathy have been investigated ex vivo by (13)C NMR in extracts of adult
      rat brain. Streptozotocin-induced diabetic or euglycemic animals received
      intravenous infusions of (1-(13)C) glucose in the absence and presence of
      trifluoroacetic acid or methionine sulfoximine, two selective inhibitors of the
      glial tricarboxylic acid cycle or of glutamine synthase, respectively. (1-(13)C)
      glucose infusions resulted in smaller (13)C incorporation in all carbons of
      cerebral glutamate, glutamine and GABA in the diabetic animals. Co-infusion of
      trifluoroacetic acid with (1-(13)C) glucose further reduced the (13)C enrichments
      in cerebral glutamate and glutamine, the decrease being larger in the diabetic
      animals than in the corresponding euglycemic controls. Methionine sulfoximine
      decreased to undetectable levels the fractional (13)C enrichment in the carbons
      of cerebral glutamine in both groups and had no significant effect on (13)C
      incorporation in glutamate and GABA, suggesting that glutamine is not the main
      precursor of glutamate and GABA. Additional animals were infused with (1,2
      (13)C(2)) acetate, a major substrate of glial metabolism. In this case, (1,2
      (13)C(2)) acetate infusions resulted in increased (13)C incorporation in all
      carbons of glutamate, glutamine and GABA in the diabetic animals. Together, these
      results reveal that diabetic encephalopathy has an important effect in astroglial
      metabolism, decreasing glucose transport and metabolism and increasing the
      relative contribution of glial oxidative metabolism to the support of
      glutamatergic and GABAergic neurotransmissions.

PMID- 14679508
TI  - Electron transfer and dynamic infrared-band coalescence: it looks like dynamic
      NMR spectroscopy, but a billion times faster.
AB  - Broadening and coalescence of infrared bands can occur due to chemical exchange
      processes occurring on very fast, femtosecond-to-picosecond timescales. One such
      fast process of recent investigation is intramolecular electron transfer in
      transition-metal complexes with strong communication between electron-donor and 
      acceptor sites. The observation of partial coalescence of metal-carbonyl
      stretching bands in hexanuclear ruthenium mixed-valence complexes due to electron
      transfer rates on the order of 10(11)-10(12) s(-1) is chronicled here. Several
      important advances have been made with the aid of dynamic infrared-band
      coalescence in these complexes, including the observation of dynamic solvent
      relaxation effects on electron-transfer rates, the determination of the
      equilibrium constant between charge-transfer isomers, and a reconsideration of
      the theory of electron transfer and delocalization in bridged, near-delocalized
      electron-transfer systems.

PMID- 14679509
TI  - Separated and aligned molecular fibres in solid state self-assemblies of
      cyclodextrin [2]rotaxanes.
AB  - The conformations of two [2]rotaxanes, each comprising alpha-cyclodextrin as the
      rotor, a stilbene as the axle and 2,4,6-trinitrophenyl substituents as the
      capping groups, have been examined in solution and in the solid state, using (1)H
      NMR spectroscopy and X-ray crystallography, respectively. In solution,
      introducing substituents onto the stilbene prevents the cyclodextrin from being
      localized over one end of the axle. Instead the cyclodextrin moves back and forth
      along the substituted stilbene. In the solid state, the axles of the rotaxanes
      form extended molecular fibres that are separated from each other and aligned
      along a single axis. The molecular fibres are strikingly similar to those formed
      by the axle component of one of the rotaxanes in the absence of the cyclodextrin,
      but in the latter case they are neither separated nor all aligned.

PMID- 14679510
TI  - Installation of a ratchet tooth and pawl to restrict rotation in a cyclodextrin
      rotaxane.
AB  - Eight new [2]rotaxanes have been prepared, incorporating an alpha-cyclodextrin as
      the rotor, a stilbene as the axle, and trinitrophenyl substituents as capping
      groups. Strategies have been devised to elaborate these by linking the rotor to
      the axle, to produce two new [1]rotaxanes. Rotational motion in a selection of
      these rotaxanes has been investigated through the application of two-dimensional
      NMR spectroscopy by performing TOCSY, DQF-COSY, ROESY and HMQC experiments. This
      has shown that a methoxyl group incorporated on the stilbene and a succinamide
      joining the stilbene and the cyclodextrin behave analogously to a ratchet tooth
      and pawl, respectively, to restrict rotation.

PMID- 14679511
TI  - Assembled dendritic titanium catalysts for enantioselective hetero-Diels-Alder
      reaction of aldehydes with Danishefsky's diene.
AB  - A new type of dendritic 2-amino-2'-hydroxy-1,1'-binaphthyl (NOBIN)-derived Schiff
      base ligands have been synthesized and applied to the titanium-catalyzed hetero
      Diels-Alder reaction of Danishefsky's diene with aldehydes. These reactions
      afforded the corresponding 2-substituted 2,3-dihydro-4H-pyran-4-ones in
      quantitative yields and with excellent enantioselectivities (up to 97.2 % ee).
      The disposition of the dendritic wedges and the dendron size in the ligands were
      found to have significant impact on the enantioselectivity of the reaction. The
      recovered dendritic catalyst could be reused without further addition of the Ti
      source or a carboxylic acid additive for at least three cycles, retaining similar
      activity and enantioselectivity. The high stability of this type of assembled
      dendritic titanium catalyst may be attributed to the stabilization effect of
      large-sized dendron units in the catalyst molecule. The other important
      phenomenon observed with this catalyst system is that a higher degree of
      asymmetric amplification has been achieved by attachment of the dendron unit to
      the chiral ligand, which represents a new advantage of dendrimer catalysts for
      asymmetric reactions using chiral ligands of lower optical purity.

PMID- 14679512
TI  - Oligosaccharide-peptide ligation of glycosyl thiolates with dehydropeptides:
      synthesis of S-linked mucin-related glycopeptide conjugates.
AB  - A chemoselective strategy for oligosaccharide-peptide ligation is described in
      which alpha-thio analogues of mucin-related glycoconjugates can be readily
      accessed through site-selective conjugate addition of complex oligosaccharide
      thiolates to dehydroalanine-containing peptides. The efficiency of the ligation
      is highlighted by the rapid convergent assembly of thio-isosteres of the four
      tumor-associated carbohydrate antigens, T(N), T, ST(N), and 2,6-ST, as a pair of
      diastereoisomers at the newly formed cysteine stereocenter. The process proceeds
      in high yield and with complete retention of the alpha-anomeric configuration.

PMID- 14679513
TI  - In situ investigations of structure-activity relationships in
      heteropolyoxomolybdates as partial oxidation catalysts.
AB  - The structural evolution of Keggin-type heteropolyoxomolybdates (HPOM) during
      thermal treatment in propene and in propene and oxygen in the temperature range
      from 300 to 773 K was investigated by in situ X-ray diffraction (XRD) and in situ
      X-ray absorption spectroscopy (XAS) combined with mass spectrometry. During
      treatment in propene or hydrogen and at reaction temperatures above 673 K, the
      initially triclinic H(3)[PMo(12)O(40)].13 H(2)O is transformed quantitatively
      into a cubic HPOM (Pn$?bar 3$m, a=11.853 A) exhibiting a long-range structure
      similar to that of the corresponding cesium salts. The treatment described
      constitutes the first readily available preparation route for a cubic HPOM
      without alkali metal ions in the structure. For both H(3)[PMo(12)O(40)] and
      Cs(2)H[PMo(12)O(40)] migration of molybdenum from the Keggin ion onto
      interstitial sites is proposed to occur in propene or hydrogen at temperatures
      above about 573 K to give thermally stable, partially reduced lacunary Keggin
      ions. During activation in propene and oxygen the onset of catalytic activity of
      H(3)[PMo(12)O(40)] and Cs(2)H[PMo(12)O(40)] at about 573 K correlates with
      partial reduction of Mo and characteristic changes in the local structure of the
      Keggin ion. The structural changes observed indicate that, similar to the
      treatment of the HPOM in propene, migration of molybdenum from the Keggin ions
      onto interstitial sites and formation of lacunary Keggin ions take place.
      Moreover, the formation of these partially reduced lacunary Keggin ions appears
      to be a prerequisite for the material to become an active heterogeneous catalyst.
      Evidently, the undistorted Keggin ion in the as-prepared HPOM has to be regarded
      as a precursor of the active catalyst.

PMID- 14679514
TI  - The (2-phenyl-2-trimethylsilyl)ethyl-(PTMSEL)-linker in the synthesis of
      glycopeptide partial structures of complex cell surface glycoproteins.
AB  - The (2-phenyl-2-trimethylsilyl)ethyl-(PTMSEL) linker represents a novel fluoride
      sensitive anchor for the solid-phase synthesis of protected peptides and
      glycopeptides. Its cleavage is achieved under almost neutral conditions using
      tetrabutylammonium fluoride trihydrate in dichloromethane thus allowing the
      construction of complex molecules sensitive to basic and acidic media commonly
      required for the cleavage of standard linker systems. The advantages of the
      PTMSEL linker are demonstrated in the synthesis of glycopeptides from the liver
      intestine (LI)-cadherin and the mucin MUC1, bearing carbohydrate moieties such as
      N-linked chitobiose or O-linked sialyl-T(N)-residues. The synthesis of these
      types of glycopeptides is difficult because they are prone to secondary structure
      formation during the synthesis on the solid phase as well as in the completely
      deprotected form. Using the PTMSEL linker these molecules are accessible by
      automated synthesis according to the Fmoc strategy without frequently observed
      side reactions such as aspartimide or diketopiperazine formation.

PMID- 14679515
TI  - Photocurrent generation in multilayer self-assembly films fabricated from water
      soluble poly(phenylene vinylene).
AB  - A novel, water-soluble, cationic PPV derivative poly[(2,5-bis(3
      bromotrimethylammoniopropoxy)-phenylene-1,4-divinylene)-alt-1,4-(2,5-bis(2-(2
      hydroxyethoxy)ethoxy))phenylene vinylene] (BH-PPV) has been synthesized by a Heck
      coupling reaction. Multilayered assemblies of the BH-PPV and the sodium salt of
      hexa(sulfobutyl)fullerenes (C(60)-HS) were fabricated successfully by an
      alternate deposition technique. The multilayer structures were studied by UV/Vis
      spectroscopy, small angle X-ray diffraction, and atomic force microscopy. The
      photoinduced charge transfer property of the self-assembled multilayer film was
      also measured by a three-electrode cell technique. A steady and rapid cathodic
      5.5 microA cm(-2) photocurrent response was measured as the irradiation of the
      multilayer film was switched on and off. Importantly, the response of on/off
      cycling is prompt and reproducible. A possible mechanism for the electron
      transfer process is proposed.

PMID- 14679516
TI  - Selection and amplification of mixed-metal porphyrin cages from dynamic
      combinatorial libraries.
AB  - Mixed metallo-porphyrin cages were selected and amplified from dynamic
      combinatorial libraries (DCLs) by using appropriate templates. The cages are
      composed of two bisphosphine substituted zinc(II) porphyrins as ligand donors and
      two rhodium(III) or ruthenium(II) porphyrins as ligand acceptors, and are
      connected through metal-phosphorus coordination. Ru and Rh porphyrins that
      display a large structural diversity were employed. The templating was achieved
      by using 4,4'-bpy, 3,3'-dimethyl-4,4'-bipyridine and benzo[lmn]-3,8
      phenanthroline, and acts through zinc-nitrogen coordination. The absolute amount
      of amplification from the DCLs is strongly dependent on the combination of the
      Ru/Rh porphyrin and the template; cages with sterically demanding porphyrins can
      only form with smaller templates. In the case of tert-butyl-substituted TPP
      (TPP=tetraphenylporphyrin), cages are not formed at all. The formation of the
      cages is usually complete within 24 h at an ambient temperature; in the case of
      the cage containing Rh(III)OEP (OEP=octaethylporphyrin) and bpy, the pseudo-first
      order rate constant of cage formation was determined to be 2.1+/-0.1x10(-4) s(-1)
      (CDCl(3), 25 degrees C). Alternatively, heating the mixtures to 65 degrees C and
      cooling to room temperature yields the cages within minutes. The (1)H NMR
      chemical shifts of several characteristic protons show large differences upon
      changing the identity of the Ru/Rh porphyrin and the central metal; this is most
      likely to arise from variations in the geometry of the cages. The X-ray crystal
      structure of a cage, which contains Rh(III)OEP as a porphyrin acceptor and bpy as
      template, demonstrates that the cages can adopt severely distorted conformations
      to accommodate the relatively short templates. An extension to mixed DCLs showed
      that only limited selectivity is displayed by the various templates. Formation of
      mixed cages that contain two different rhodium porphyrins prevents effective
      selection, although the kinetic lability of the systems allows for some
      amplification. This lability, however, also prevents isolation of the individual
      cages. Removal of the template leads to re-equilibration, thus the templates act
      as scaffolds to keep the structures intact.

PMID- 14679517
TI  - Palladium-catalyzed highly regio- and stereoselective addition of organoboronic
      acids to allenes in the presence of AcOH.
AB  - The Pd(0)-catalyzed regio- and stereoselective addition of organoboronic acids to
      allenes leads to stereodefined tri- or tetrasubstituted alkenes. Furthermore,
      this method shows high substitutent-loading capability and tolerance of various
      substitutents. A hydropalladation-Suzuki coupling mechanism, which may account
      for the regio- and stereoselectivity, is proposed.

PMID- 14679518
TI  - Valence charge concentrations, electron delocalization and beta-agostic bonding
      in d0 metal alkyl complexes.
AB  - In this paper we describe a range of model d(0) metal ethyl compounds and related
      complexes, studied by DFT calculations and high resolution X-ray diffraction. The
      concept of ligand-opposed charge concentrations (LOCCs) for d(0) metal complexes
      is extended to include both cis-and trans-ligand-induced charge concentrations
      (LICCs) at the metal, which arise as a natural consequence of covalent metal
      ligand bond formation in transition metal alkyl complexes. The interplay between
      locally induced sites of increased Lewis acidity and an ethyl ligand is crucial
      to the development of a beta-agostic interaction in d(0) metal alkyl complexes,
      which is driven by delocalization of the M-C bonding electrons. Topological
      analysis of theoretical and experimental charge densities reveals LICCs at the
      metal atom, and indicates delocalization of the M-C valence electrons over the
      alkyl fragment, with depletion of the metal-directed charge concentration (CC) at
      the alpha-carbon atom, and a characteristic ellipticity profile for the C(alpha)
      C(beta) bond. These ellipticity profiles and the magnitude of the CC values at
      C(alpha) and C(beta) provide experimentally observable criteria for assessing
      quantitatively the extent of delocalization, with excellent agreement between
      experiment and theory. Finally, a concept is proposed which promises systematic
      control of the extent of C-H activation in agostic complexes.

PMID- 14679519
TI  - Novel podands and macrocycles with diacetal (tetraoxadecalin) cores: synthesis,
      structure, stereochemistry and cation inclusion.
AB  - A series of functionalized 2,6-dialkyl-cis-1,3,5,7-tetraoxadecalin podands (3-10,
      alkyl = hydroxy-, mesyloxy-, halo-, azido- and aminomethyl and -ethyl) were
      prepared, characterized, and used as precursors for a new and interesting class
      of macrocycles and cryptands (12-21), with the aim to use these as host-guest
      inclusion systems. Extensive spectroscopic work was performed, structural
      endorsement was obtained from X-ray diffraction analyses and further insight into
      the structures was obtained from theoretical/computational studies. A number of
      macrocycles in the series exhibited good complexation with alkaline-earth metal
      ions.

PMID- 14679520
TI  - Efficient synthesis of high molar mass, first- to fourth-generation distributed
      dendronized polymers by the macromonomer approach.
AB  - A homologous series of first- to fourth-generation (G1-G4) dendronized
      macromonomers, 5, 7, 10, and 12, was synthesized, and their polymerization
      behavior under radical conditions investigated. These conditions were thermally
      induced radical polymerization (TRP) and atom-transfer radical poymerization
      (ATRP). TRP was applied to all monomers and gave polymers PG1-PG4, whose molar
      masses range from several millions for PG1 to estimated several hundreds of
      thousands for PG2 and PG3, and to the oligomeric regime for PG4. ATRP was applied
      only to the G1 and G2 monomers 5 and 7. Kinetic studies on monomer 5 provide
      evidence that its polymerization proceeds in a controlled fashion. The highest
      monomer-to-initiator ratios which still gave monomodal molar mass distributions
      were 300:1 (for 5) and 100:1 (for 7), which correspond to achievable molar mass
      regime for PG1 and PG2 of approximately M(n)=100 000 (DP(calcd)(PG1)=200,
      DP(calcd)(PG2)=90). The polydispersities lie in the usual range (PDI=1.1-1.2).
      The molar masses were determined by GPC in DMF with calibration against absolute
      molar masses of PG1 determined by light scattering.

PMID- 14679521
TI  - 2-phosphanylphenolate nickel catalysts for the polymerization of ethylene.
AB  - The previously unknown methallylnickel 2-diorganophosphanylphenolates (R=Ph,
      cHex) were synthesized and found to catalyze the polymerization of ethylene. To
      explore the potential for ligand-tuning, a variety of P-alkyl- and P-phenyl-2
      phosphanylphenols was synthesized and allowed to react with [Ni(cod)(2)] (cod=1,5
      cyclooctadiene) or with NiBr(2).DME and NaH. The complexes formed in situ with
      [Ni(cod)(2)] are generally active as ethylene polymerization catalysts with all
      the ligands tested, whereas the latter systems are inactive when 2
      dialkylphosphanylphenols are applied. M(w) values, ranging from about 1000 to
      about 100000 g mol(-1), increase for various R(2)P groups in the order R=Ph<Et
      approximately tBu<iPr<cHex, while aryloxy substituents usually diminish the
      molecular weights. Increasing basicity of P- or aryloxy substituents usually
      leads to increasing turnover numbers. The polymers are high density polyethylene
      (HDPE) with low methyl and sometimes low long-chain branching. Investigation of
      the influence of the solvent shows that the catalysts are stabilized by some
      oxygen-containing Lewis bases as well as by olefins. The catalysts are tolerant
      to water, in particular the 2-dicyclohexylphosphanylphenolate nickel catalyst,
      which in THF-water (1:1) gives HDPE with M(w)=39000, M(n)=14500 g mol(-1).
      Additives of tetrahydrothiophene or pyridine do not inhibit the catalyst, but
      decrease the reaction rate and the molecular weight of the polymers.

PMID- 14679522
TI  - Au nanoparticle-enhanced surface plasmon resonance sensing of biocatalytic
      transformations.
AB  - N-(3-Aminopropyl)-N'-methyl-4,4'-bipyridinium is coupled to tiopronin-capped Au
      nanoparticles (diameter ca. 2 nm) to yield methyl(aminopropyl)viologen
      functionalized Au nanoparticles (MPAV(2+)-Au nanoparticles). In situ
      electrochemical surface plasmon resonance (SPR) measurements are used to follow
      the electrochemical deposition of the bipyridinium radical cation modified Au
      nanoparticles on an Au-coated glass surface and the reoxidation and dissolution
      of the bipyridinium radical cation film. The MPAV(2+)-functionalized Au
      nanoparticles are also employed for the amplified SPR detection of NAD(+) and
      NADH cofactors. By SPR monitoring the partial biocatalyzed dissolution of the
      bipyridinium radical cation film in the presence of diaphorase (DP) NAD(+) is
      detected in the concentration range of 1x10(-4) M to 2x10(-3) M. Similarly, the
      diaphorase-mediated formation of the bipyridinium radical cation film on the Au
      coated glass surface by the reduction of the MPAV(2+)-functionalized Au
      nanoparticles by NADH is used for the amplified SPR detection of NADH in the
      concentration range of 1x10(-4) M to 1x10(-3) M.

PMID- 14679523
TI  - Diferratricarbaboranes of the subcloso-[(eta5-C5H5)2Fe2C3B8H11] type, the first
      representatives of the 13-vertex dimetallatricarbaborane series.
AB  - Treatment of the [2-Cp-9-tBuNH-closo-2,1,7,9-FeC(3)B(8)H(10)] (1)
      ferratricarbollide (Cp = eta(5)-C(5)H(5) (-)) with Na(+) C(10)H(8) (-) in 1,2
      dimethoxyethane (DME) at room temperature produced an air-sensitive transient
      anion with a tentatively identified nido-[tBuNH-CpFeC(3)B(8)H(10)](2-)
      constitution. In-situ reaction of this low-stability ion with [CpFe(CO)(2)I] or
      [CpFe(CO)(2)](2) generated three violet diferratricarbaboranes identified as
      paramagnetic subcloso complexes [4,5-Cp(2-)-4,5,1,6,7-Fe(2)C(3)B(8)H(11)] (2;
      yield 2 %), [4,5-Cp(2-)-4,5,1,7,12-Fe(2)C(3)B(8)H(11)] (3; yield 2 %), and [7
      tBuNH-4,5-Cp(2-)-4,5,1,7,12-Fe(2)C(3)B(8)H(10)] (4; yield 14 %). These first
      representatives of the 13-vertex dimetallatricarbaborane family were
      characterized by EPR and IR spectroscopy, and mass spectrometry, and their
      structures were determined by X-ray diffraction analysis.

PMID- 14679524
TI  - X-ray structure and circular dichroism of pure rotamers of bis[guanosine-5'
      monophosphate(-1)](N,N,N',N'-tetramethylcyclohexyl-1,2-diamine)platinum(II)
      complexes that have R,R and S,S configurations at the asymmetric diamine.
AB  - The use of a sterically hindered diamine ligand (Me(4)DACH) has allowed for the
      first time, the isolation and characterization, both in the solid state (X-ray
      crystallography) and in solution (circular dichroism), of pure DeltaHT rotamers
      of [Pt(Me(4)dach)(5'-GMP)(2)] (compounds 1 and 2 for R,R and S,S configurations
      of the Me(4)DACH ligand, respectively). Comparison of the CD spectra obtained for
      each rotamer, which differ only in the chirality of the Me(4)DACH ligand (R,R or
      S,S) or in the chirality of the HT conformation (Delta or Lambda), allowed us to
      conclude that, in the 200-350 nm range, the contributions to the overall CD
      spectrum that stem from diamine chirality and diamine-induced chirality of
      platinum d--d transitions or from sugar chirality are negligible relative to the
      exciton chiral coupling that occurs for pi-pi* transitions of the cis guanines.
      Accurate molecular structures of 1.10 D(2)O and 2.14 D(2)O (conventional
      crystallographic agreement indexes R(1) convergent to 2.07 % and 2.18 %,
      respectively) revealed that the crystallized rotamers have a DeltaHT conformation
      that is in agreement with all previously reported X-ray structures of
      [Pt(diamine)(nucleos(t)ide)(2)] complexes. This conformation allows the 5'
      phosphate to be located in proximity to the Me(4)DACH ligand so that (P)O...HC(N)
      hydrogen-bond interactions exists in both complexes. For both structures, the
      canting of the guanine planes on the coordination plane is right-handed (R;
      canting angle (Phi) of 80.9 degrees and 73.2 degrees, respectively); this
      indicates that the canting direction is driven by the HT conformation chirality
      (Delta for both compounds) and not by the chirality of the carrier ligand
      (different for the two compounds). Density functional theory analysis of the
      conformational space as a function of Phi indicated a good agreement between the
      computed and experimental structures. The increase in energy for Phi values below
      65 degrees and 55 degrees (for 1 and 2, respectively) is mainly due to the short
      intramolecular contacts between C(8)H and the cis N-Me groups on the same side of
      the platinum coordination plane.

PMID- 14679525
TI  - A bifunctional platinum(II) complex capable of intercalation and hydrogen-bonding
      interactions with DNA: binding studies and cytotoxicity.
AB  - The interactions of [Pt(CNN)(4-dpt)]PF(6), (1; 4-dpt=2,4-diamino-6-(4-pyridyl)
      1,3,5-triazine, HCNN=6-phenyl-2,2'-bipyridine) with double-stranded DNA, poly(dA
      dT)(2), and poly(dG-dC)(2) were examined by spectroscopic, electrophoretic, and
      hydrodynamic methods. The spectroscopic data were analyzed with McGhee, van't
      Hoff, and Gibbs-Helmholtz equations. In a comparative study, [Pt(CNN)(py)]PF(6)
      (2; py=pyridine) was prepared and the nature of its binding towards DNA was
      investigated [preliminary results: ChemBioChem 2003, 4, 62-68]. For reactions
      with calf thymus DNA at 20 degrees C, the intrinsic binding constants for 1 and 2
      are (4.6+/-0.2)x10(5) and (2.3+/-0.3)x10(4) mol(-1) dm(3), respectively. Results
      of DNA-binding reactions revealed that 1 and 2 preferentially bind to the AT
      sequence of duplex DNA. Intercalation is the preferred binding mode for 2,
      whereas both intercalation and minor-groove binding are observed for 1. Complex 1
      is cytotoxic against a number of carcinoma cell lines, including KB-3-1, CNE-3,
      and HepG2, and remains potent against multidrug- or cisplatin-resistant KB-V-1
      and CNE1 cell lines, for which the resistance ratios are 1.6 and 1.5,
      respectively. Importantly, 1 is almost an order of magnitude less toxic to the
      normal cell line CCD-19Lu (IC(50)=176+/-1.7 microM) and it selectively induced
      apoptosis leading to cancer cell death with less than 5 % detectable necrosis.

PMID- 14679526
TI  - The first catalytic highly enantioselective alkylation of ketimines--a novel
      approach to optically active quaternary alpha-amino acids.
AB  - A series of novel ketimines with intrinsic protecting group anchoring was
      synthesized and allowed to react with various silylketene acetals in the presence
      of 5-10 mol % of a chiral Zn(OTf)(2)-(R,R)-Ph-pybox-aqua complex. The
      corresponding optically active quaternary alpha-amino acid derivatives were
      obtained in high yields and with enantioselectivities ranging from 34 % up to 95
      % ee. The catalyst was studied by (1)H NMR spectroscopy and X-ray
      crystallography, and a dynamic equilibrium of two species was identified in
      solution. These are a homo-chiral 1:2 metal-ligand complex and a 1:1 metal-ligand
      complex, of which the latter is expected to be the actual catalyst of the
      diastereo- and enantioselective reaction. A strong positive nonlinear effect was
      observed due to the formation of a catalytically inactive 1:2 metal-ligand hetero
      chiral complex. On the basis of DFT calculations and the absolute stereochemistry
      of the products, simultaneous coordination of the imino electrophile and a single
      molecule of H(2)O to the chiral Lewis acid complex is proposed. Coordination of
      the imine-nitrogen atom in the axial position of an octahedral complex can
      account for the facial selectivity as well as the diastereoselectivity observed.

PMID- 14679527
TI  - Structural basis for vapoluminescent organoplatinum materials derived from
      noncovalent interactions as recognition components.
AB  - The spectroscopic properties and crystal structures of a series of platinum(II)
      complexes bearing functionalized sigma-alkynyl groups, namely [(tBu(2)bpy)Pt(C
      triple bond CAr)(2)] (tBu(2)bpy = 4,4'-bis-tert-butyl-2,2'-bipyridine, Ar = 4
      pyridyl, 1; 3-pyridyl, 2; 2-pyridyl, 3; 4-ethynylpyridyl, 4; 2-thienyl, 5;
      pentafluorophenyl, 6) have been studied. Solid-state emissions of 1 and 6 are
      dependent on their crystallinity. Reversible and selective vapoluminescence was
      observed for 1 and 6 in the presence of chlorocarbon vapors. For solid 1,
      dramatic enhancement of green luminescence is observed upon sorption of
      CH(2)Cl(2) or CHCl(3) vapor. The excimeric orange emission for solid 6 is
      switched to monomeric green emission upon exposure to CH(2)Cl(2) vapor. The
      luminescent responses of a thin film of 1 towards various organic vapors have
      also been examined. In the crystallographically determined structure of
      1.CH(2)Cl(2), the bis(acetylide) moiety acts as the receptor berth for a
      CH(2)Cl(2) molecule through concerted C-H.pi(C triple bond C) interactions, while
      Cl.Cl interactions connect the CH(2)Cl(2) molecules into infinite linear chains.
      The observed crystal lattices are arranged into scaffolds of varying porosity by
      weak C-H...N(py) (1.CH(2)Cl(2), 1.CH(3)CN, 4.DMF) and C-H...F-C (6, 6.CH(3)CN)
      interactions. The correlation between the crystal structures of 1.CH(2)Cl(2),
      1.CH(3)CN, 2, 4.DMF, 5, 6, and 6.CH(3)CN and their vapoluminescence suggests that
      weak nonconventional hydrogen-bonding interactions preside over the reversible
      sensing and signalling processes.

PMID- 14679528
TI  - Synthesis of conjugated polyrotaxanes.
AB  - A series of conjugated polyrotaxane insulated molecular wires are synthesised by
      aqueous Suzuki polymerisation, using hydrophobic binding to promote threading of
      the cyclodextrin units. These polyrotaxanes have conjugated polymer cores based
      on poly(para-phenylene), polyfluorene, and poly(diphenylene-vinylene), threaded
      through 0.9-1.6 cyclodextrins per repeat unit. Bulky naphthalene-3,6-disulfonate
      endgroups prevent the macrocycles from slipping off the conjugated polymer
      chains. Dialysis experiments show that the cyclodextrins become unthreaded only
      if smaller stoppers are used. MALDI TOF mass spectra detect oligomers with up to
      ten threaded cyclodextrins, and reveal the presence of some defects that result
      for oxidative homo-coupling of boronic acids. Weight-average molecular weights
      were determined by analytical ultracentrifugation, demonstrating that step-growth
      polymerisation is efficient enough to achieve degrees of polymerisation up to
      approximately 20 repeat units (84 para-phenylenes). The fluorescence spectra of
      these polyrotaxanes indicate that the presence of the threaded cyclodextrin
      macrocycles reduces the flexibility of the conjugated polymer pi-systems. Both
      the solution and the solid-state photoluminescence quantum yields are enhanced
      upon threading of the conjugated polyaromatic cores through alpha- or beta
      cyclodextrins, and the emission spectra of the polyrotaxanes are blue-shifted
      compared to the corresponding unthreaded polymers. The greater weight of the 0-0
      transition in the emission spectra, as well as the smaller Stokes shift, indicate
      that the polyrotaxanes are more rigid than the unthreaded polymers.

PMID- 14679529
TI  - Total synthesis and biological evaluation of (-)apicularen A and analogues
      thereof.
AB  - Apicularen A (1) and related benzolactone acylenamines belong to a growing class
      of novel natural products possessing highly cytotoxic properties. The challenging
      structure of 1 includes a 10-membered macrolactone ring, a tetrahydropyran
      system, an o,m-substituted phenol and a doubly unsaturated acyl group attached on
      the side chain enamine functionality. The total synthesis of apicularen A
      described herein involves a strategy equivalent to its proposed biosynthesis and
      entails a reiterative two-step procedure featuring allylation and ozonolytic
      cleavage to grow the molecule's chain by one acetate unit at a time. The
      developed synthetic technology was applied to the construction of a series of
      apicularen A analogues whose biological evaluation established a set of structure
      activity relationships in this new area of potential importance in cancer
      chemotherapy.

PMID- 14679530
TI  - Generation and coupling of [Mn(dmpe)2(C triple bond CR)(C triple bond C)]*
      radicals producing redox-active C4-bridged rigid-rod complexes.
AB  - The symmetric d(5) trans-bis-alkynyl complexes [Mn(dmpe)(2)(C triple bond
      CSiR(3))(2)] (R = Me, 1 a; Et, 1 b; Ph, 1 c) (dmpe = 1,2
      bis(dimethylphosphino)ethane) have been prepared by the reaction of
      [Mn(dmpe)(2)Br(2)] with two equivalents of the corresponding acetylide LiC triple
      bond CSiR(3). The reactions of species 1 with [Cp(2)Fe][PF(6)] yield the
      corresponding d(4) complexes [Mn(dmpe)(2)(C triple bond CSiR(3))(2)][PF(6)] (R =
      Me, 2 a; Et, 2 b; Ph, 2 c). These complexes react with NBu(4)F (TBAF) at -10
      degrees C to give the desilylated parent acetylide compound [Mn(dmpe)(2)(C triple
      bond CH)(2)][PF(6)] (6), which is stable only in solution at below 0 degrees C.
      The asymmetrically substituted trans-bis-alkynyl complexes [Mn(dmpe)(2)(C triple
      bond CSiR(3))(C triple bond CH)][PF(6)] (R = Me, 7 a; Et, 7 b) related to 6 have
      been prepared by the reaction of the vinylidene compounds [Mn(dmpe)(2)(C triple
      bond CSiR(3))(C=CH(2))] (R = Me, 5 a; Et, 5 b) with two equivalents of
      [Cp(2)Fe][PF(6)] and one equivalent of quinuclidine. The conversion of
      [Mn(C(5)H(4)Me)(dmpe)I] with Me(3)SiC triple bond CSnMe(3) and dmpe afforded the
      trans-iodide-alkynyl d(5) complex [Mn(dmpe)(2)(C triple bond CSiMe(3))I] (9).
      Complex 9 proved to be unstable with regard to ligand disproportionation
      reactions and could therefore not be oxidized to a unique Mn(III) product, which
      prevented its further use in acetylide coupling reactions. Compounds 2 react at
      room temperature with one equivalent of TBAF to form the mixed-valent species
      [[Mn(dmpe)(2)(C triple bond CH)](2)(micro-C(4))][PF(6)] (11) by C-C coupling of
      [Mn(dmpe)(2)(C triple bond CH)(C triple bond C*)] radicals generated by
      deprotonation of 6. In a similar way, the mixed-valent complex [[Mn(dmpe)(2)(C
      triple bond CSiMe(3))](2)(micro-C(4))][PF(6)] [12](+) is obtained by the reaction
      of 7 a with one equivalent of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene). The
      relatively long-lived radical intermediate [Mn(dmpe)(2)(C triple bond CH)(C
      triple bond C*)] could be trapped as the Mn(I) complex [Mn(dmpe)(2)(C triple bond
      CH)(triple bond C-CO(2))] (14) by addition of an excess of TEMPO (2,2,6,6
      tetramethyl-1-piperidinyloxy) to the reaction mixtures of species 2 and TBAF. The
      neutral dinuclear Mn(II)/Mn(II) compounds [[Mn(dmpe)(2)(C triple bond
      CR(3))](2)(micro-C(4))] (R = H, 11; R = SiMe(3), 12) are produced by the
      reduction of [11](+) and [12](+), respectively, with [FeCp(C(6)Me(6))]. [11](+)
      and [12](+) can also be oxidized with [Cp(2)Fe][PF(6)] to produce the dicationic
      Mn(III)/Mn(III) species [[Mn(dmpe)(2)(C triple bond CR(3))](2)(micro
      C(4))][PF(6)](2) (R = H, [11](2+); R = SiMe(3), [12](2+)). Both redox processes
      are fully reversible. The dinuclear compounds have been characterized by NMR, IR,
      UV/Vis, and Raman spectroscopies, CV, and magnetic susceptibilities, as well as
      elemental analyses. X-ray diffraction studies have been performed on complexes 4
      b, 7 b, 9, [12](+), [12](2+), and 14.

PMID- 14679531
TI  - A definitive synthesis of D-myo-inositol 1,4,5,6-tetrakisphosphate and its
      enantiomer D-myo-inositol 3,4,5,6-tetrakisphosphate from a novel butane-2,3
      diacetal-protected inositol.
AB  - New and rapid syntheses of the enantiomeric intracellular signalling molecules d
      myo-inositol 1,4,5,6-tetrakisphosphate (1 a) and D-myo-inositol 3,4,5,6
      tetrakisphosphate (1 b) are described. The synthetic strategy employs the novel
      butane-2,3-diacetal-protected (BDA-protected) myo-inositol (+/-)-3 ab, directly
      accessible from myo-inositol on a large scale, and an optical resolution with
      diastereoisomeric (R)-(-)-acetylmandelate esters. The X-ray crystal structure of
      (+/-)-4, an unusual side product of acid-catalysed reaction of myo-inositol with
      butanedione is also presented, and the absolute configurations of 1 a and 1 b are
      definitively assigned by conversion of key precursors into (+)-bornesitol and L
      iditol hexaacetate, respectively. Biological activity of synthetic 1 b was
      confirmed in comparison with the natural polyphosphate.

PMID- 14679532
TI  - Solvothermal syntheses of high-nuclearity vanadium(III) clusters.
AB  - Superheating alcohol solutions of simple trimetallic vanadium(III) precursors
      gives the octa- and decametallic vanadium(III) clusters
      [V(8)(OEt)(8)(OH)(4)(O(2)CPh)(12)] (1) and [V(10)(OMe)(20)(O(2)CMe)(10)] (2).
      Cluster 2 is the largest vanadium(III) cluster synthesised to date. Thus
      solvothermal synthetic techniques are an excellent route to high-nuclearity
      vanadium(III) clusters. Both 1 and 2 consist of a planar or near-planar array of
      V(III) ions. The metal ions in 1 are bridged by either a micro(2)-hydroxide and
      two micro(2)-benzoate groups or two micro(2)-ethoxides and a micro(2)-benzoate
      groups, the two bridging arrangements alternating around the ring. In 2 each pair
      of neighbouring metal ions is bridged by two micro(2)-methoxides and a micro(2)
      acetate, and this molecule is the V(III) analogue of Lippard's famous "ferric
      wheel". Preliminary magnetic susceptibility studies show the exchange coupling in
      both complexes to be antiferromagnetic in nature, with the coupling stronger in 1
      than in 2.

PMID- 14679538
TI  - Re-engineering the genetic code: combining molecular biology and organic
      chemistry.

PMID- 14679539
TI  - Carbon nanotubes by quantitative solid-state conversion of an organometallic
      precursor.

PMID- 14679540
TI  - The role of radicals in metal-assisted oxygenation reactions.
AB  - The oxo-functionalization of organic substrates with the aid of metal oxo
      moieties is of fundamental importance not only in nature but also in academic and
      industrial research. Nevertheless the corresponding reaction mechanisms remain
      among the most enigmatic in chemistry and few of them are understood in detail.
      Recent research efforts have resulted in significantly improved information: in
      the cases of many oxygenation reactions evidence has been provided for the
      occurrence radical intermediates, even though the high selectivity observed
      suggests to a different mechanism. Examples stem from various areas of chemistry
      and include processes involving molecular metal oxo complexes, gas-phase and
      matrix-isolated species, metalloenzymes, and solid-state oxide surfaces. This
      review treats this seemingly wide variety of systems with the aim of providing an
      overview of common reactivity patterns and principles, as well as open problems.

PMID- 14679541
TI  - N2(SiCl3)4-A tetrakissilylhydrazine as an unexpected product of the reaction
      between N2 and SiCl4.

PMID- 14679542
TI  - Stereochemically defined osmium centers from asymmetric diamination of olefins:
      mechanistic implications for osmium-mediated acrylate functionalization.

PMID- 14679543
TI  - Mechanism of the aliphatic hydroxylation mediated by a bis(micro
      oxo)dicopper(III) complex.

PMID- 14679544
TI  - Simple synthesis of poly(acetylene) latex particles in aqueous media.

PMID- 14679545
TI  - Development of a high-throughput screen for protein catalysts: application to the
      directed evolution of antibody aldolases.

PMID- 14679546
TI  - Fluorinated DNA bases as probes of electrostatic effects in DNA base stacking.

PMID- 14679547
TI  - Horseshoes, rings, and distorted rings: studies of cyclic chromium-fluoride
      cages.

PMID- 14679548
TI  - Anionic amido N-heterocyclic carbenes: synthesis of covalently tethered
      lanthanide-carbene complexes.

PMID- 14679549
TI  - High-throughput screening by using a blue-fluorescent antibody sensor.

PMID- 14679550
TI  - Palladium-catalyzed DYKAT of vinyl epoxides: enantioselective total synthesis and
      assignment of the configuration of (+)-Broussonetine G.

PMID- 14679551
TI  - Assembling metal clusters with covalent linkers: synthesis and structure of a
      quasi-planar Pt18 dendrimer containing five clusters connected by sigma-alkynyl
      spacers.

PMID- 14679552
TI  - Efficient palladium-catalyzed coupling of aryl chlorides and tosylates with
      terminal alkynes: use of a copper cocatalyst inhibits the reaction.

PMID- 14679553
TI  - A route to the thapsigargins from (S)-carvone providing a substrate-controlled
      total synthesis of trilobolide, nortrilobolide, and thapsivillosin F.

PMID- 14679554
TI  - Chiral, porous, hybrid solids for highly enantioselective heterogeneous
      asymmetric hydrogenation of beta-keto esters.

PMID- 14679555
TI  - Hepta- and octacoordinate boron in molecular wheels of eight- and nine-atom boron
      clusters: observation and confirmation.

PMID- 14679556
TI  - Structurally defined catalysts for enantioselective oxidative coupling reactions.

PMID- 14679557
TI  - DNA topoisomerase inhibitor acutissimin a and other flavano-ellagitannins in red
      wine.

PMID- 14679558
TI  - Multiple levels of order in linked disc-rod liquid crystals.

PMID- 14679559
TI  - A nanothermometer based on the different pi stackings of B- and Z-DNA.

PMID- 14679560
TI  - Intramolecular cross-linking of helical folds: an approach to organic nanotubes.

PMID- 14679562
TI  - High-throughput separation of DNA and proteins by three-dimensional geometry gel
      electrophoresis: feasibility studies.
AB  - We report a novel separation method that is applicable to both DNA and protein
      samples, based on electrophoresis in a three-dimensional (3-D) geometry. In
      contrast to conventional electrophoresis, samples are applied in a two
      dimensional, planar array to one of the surfaces of a 3-D geometry separation
      medium. Loading onto a plane results in a very high sample capacity. Sample
      migration and separation occur along the third spatial dimension, which is
      perpendicular to the loading plane. The key problem of electrophoresis in a 3-D
      geometry separation setup is that temperature gradients are caused by Joule's
      heat, affecting the electrical conductivity and viscosity of the separation
      medium. A means of achieving straight sample migration under these circumstances
      is to force heat flow through the separation medium parallel to the axis of
      sample migration. This can be done by dissipating the heat via the electrode
      sides of the gel and blocking any other heat transfer. The separation of DNA and
      proteins by this method has been tested using agarose gel electrophoresis,
      polyacrylamide gel electrophoresis, and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Data were acquired off-line by conventional staining methods as
      well as on-line by detection of laser-induced fluorescence. We describe how to
      excise samples from the separation medium for preparative purposes. Possible
      unique applications of this 3-D geometry electrophoresis separation method are
      also discussed.

PMID- 14679563
TI  - A novel thermogelling matrix for microchannel DNA sequencing based on poly-N
      alkoxyalkylacrylamide copolymers.
AB  - We have developed a novel class of thermogelling polymer networks based on poly-N
      alkoxyalkylacrylamides, and demonstrated their use as DNA sequencing matrices for
      high-throughput microchannel electrophoresis in capillary arrays. Polymers and
      copolymers of N-ethoxyethylacrylamide (NEEA) and N-methoxyethylacrylamide (NMEA)
      were synthesized by aqueous-phase free-radical polymerization and characterized
      by tandem gel permeation chromatography-multi-angle laser light scattering. These
      copolymer matrices exhibit "re-entrant"-type volume phase transitions, forming
      entangled networks with high shear viscosity at low (< 20 degrees C) and high (>
      35 degrees C) temperatures, and undergoing a "coil-to-globular", lower critical
      solution temperature (LCST)-like phase transition over an intermediate
      temperature range (20-35 degrees C). Hence, matrix viscosity is relatively low at
      room temperature (25 degrees C), and increases rapidly above 35 degrees C. The
      material properties and phase behavior of these thermogelling polymer networks
      were studied by steady-shear rheometry. These matrices are easily loaded into
      capillary arrays at room temperature while existing as viscous fluids, but
      thermogel above 35 degrees C to form transparent hydrogels via a thermo
      associative phase transition. The extent of the intermediate viscosity drop and
      the final viscosity increase depends on the composition of the copolymers. DNA
      sequencing by capillary array electrophoresis with four-color laser-induced
      fluorescence (LIF) detection shows that these thermogelling networks provide
      enhanced resolution of both small and large DNA sequencing fragments and longer
      sequencing read lengths, in comparison to appropriate control (closely related,
      nonthermogelling) polymer networks. In particular, a copolymer comprised of 90%
      w/w NMEA and 10% w/w NEEA, with a molecular mass of approximately 2 MDa, delivers
      around 600 bases at 98.5% base-calling accuracy in 100 min of electrophoresis.

PMID- 14679564
TI  - Sparsely cross-linked "nanogels" for microchannel DNA sequencing.
AB  - We have developed sparsely cross-linked "nanogels", sub-colloidal polymer
      structures composed of covalently linked, linear polyacrylamide chains, as novel
      DNA sequencing matrices for capillary electrophoresis. The presence of covalent
      cross-links affords nanogel matrices with enhanced network stability relative to
      standard, linear polyacrylamide (LPA), improving the separation of large DNA
      fragments. Nanogels were synthesized via inverse emulsion (water-in-oil)
      copolymerization of acrylamide and N,N-methylenebisacrylamide (Bis). In order to
      retain the fluidity necessary in a replaceable polymer matrix for capillary array
      electrophoresis (CAE), a low percentage of the Bis cross-linker (< 10(-4) mol%)
      was used. Nanogels were characterized by multiangle laser light scattering and
      rheometry, and were tested for DNA sequencing by CAE with four-color laser
      induced fluorescence (LIF) detection. The properties and performance of nanogel
      matrices were compared to those of a commercially available LPA network, which
      was matched for both weight-average molar mass (Mw) and extent of interchain
      entanglements (c/c*). Nanogels presented in this work have an average radius of
      gyration of 226 nm and a weight-average molar mass of 8.8 x 10(6) g/mol. At
      concentrations above the overlap threshold, nanogels form a clear, viscous
      solution, similar to the LPA matrix (Mw approximately 8.9 x 10(6) g/mol). The two
      matrices have similar flow and viscosity characteristics. However, because of the
      physical network stability provided by the internally cross-linked structure of
      the nanogels, a substantially longer read length ( approximately 63 bases, a
      10.4% improvement) is obtained with the nanogel matrix at 98.5% accuracy of base
      calling. The nanogel network provides higher-selectivity separation of ssDNA
      sequencing fragments longer than 375 bases. Moreover, nanogel matrices require
      30% less polymer per unit volume than LPA. This is the first report of a
      sequencing matrix that provides better performance than LPA, in a side-by-side
      comparison of polymer matrices matched for Mw and extent of interchain
      entanglements.

PMID- 14679565
TI  - Carbon nanotubes as separation carrier in capillary electrophoresis.
AB  - The utility and versatility of carboxylic single-walled carbon nanotubes (c-SWNT)
      in capillary electrophoresis (CE) is demonstrated, using as model solutes
      homologues and structural isomers. In the case of homologues of caffeine and
      theobromine, distinct changes in the electrophoretic parameters occur at a
      critical concentration of c-SWNT in the run buffer. It is suggested that the c
      SWNT of a definite concentration could form a network in the run buffer as a
      pseudostationary phase on the basis of the unique tubule structure, providing a
      different separation from sodium dodecyl sulfate (SDS) micelles. In the case of
      structural isomers of catechol and hydroquinone, differing from the homologues,
      it is mainly attributable to the functional groups on the c-SWNT that have an
      effect on the electrophoretic behaviors by forming intermolecular hydrogen
      bonding with analytes. Furthermore, aggregated c-SWNT serve as anticonvective
      media and minimize solute diffusion contributing to zone broadening. The presence
      of charged c-SWNT suppressed the electrodiffusion and decreased the adsorption
      between capillary wall and solutes, which led to better peak shapes of isomers.

PMID- 14679566
TI  - Piperazine quaternary diammonium salts as additives to background electrolytes in
      capillary zone electrophoresis.
AB  - The differential behavior of five different quaternary mono- and diammonium
      salts, among the 18 investigated, in modulating the electroendoosmotic flow (EOF)
      and analyte separations in capillary zone electrophoresis is evaluated. It is
      found that quaternary diammonium salts with positive charges separated by more
      than four carbon atoms, while exhibiting a very strong affinity for
      chromatographic silica beads, to the point of exhibiting Rf values close to zero,
      display, on the contrary, a very poor affinity for the silica wall of
      capillaries. Compounds separated only by a C2 unit (i.e., 1,4-dialkyl-1,4
      diazoniabicyclo[2,2,2,]octane, salts 17 and 18) show high Rf values due to strong
      ion pair association. The unique behavior of quaternary monoammonium salts
      possessing an iodinated alkyl (butyl or octyl) tail (i.e., 1, 6, and 7) is
      attributed to their ability to be covalently affixed to the silica wall via
      alkylation of ionized silanols at alkaline pH values. They thus strongly modulate
      and typically invert the EOF, even when not present in the background
      electrolyte. On the contrary, all diammonium salts, devoid of such alkyl tails,
      are unable to modulate the EOF and to prevent analyte binding to the silica wall,
      since they are rapidly removed from the wall by the voltage gradient. However, if
      added in small amount to the background electrolyte, they offer excellent
      separations of mixtures of very similar organic acids and prevent any interaction
      with the capillary wall.

PMID- 14679567
TI  - Capillary electrophoresis of synthetic peptide standards varying in charge and
      hydrophobicity.
AB  - A mixture of eight structurally closely related synthetic peptides as capillary
      electrophoretic (CE) standards is introduced. The almost identical mass-to-charge
      ratio of the standards, coupled with their random-coil (i.e., no secondary
      structure) nature, offer a potent analytical test for CE to separate peptides
      varying only subtly in hydrophobicity. Parameters varied to effect a separation
      included background electrolyte concentration, temperature, applied voltage in
      capillary zone electrophoresis (CZE in uncoated capillaries), as well as the
      introduction of hydrophobic mechanisms to the separation either through the use
      of micelles or C8-coated capillaries. Our step-by-step approach culminated in an
      optimized combination of a CZE mechanism for separation of differently charged
      peptide groups (based on common mass-to-charge ratio) and an ion-pairing
      mechanism (effecting a separation within each group of identically charged
      peptides), which we have termed ion-interaction CZE or II-CZE. The study clearly
      shows how the peptide standards allow an excellent assessment of the resolving
      power of CE.

PMID- 14679568
TI  - Copolymerized polymeric surfactants: characterization and application in micellar
      electrokinetic chromatography.
AB  - An achiral monomeric surfactant (sodium 10-undecenyl sulfate, SUS) and a chiral
      surfactant (sodium 10-undecenoyl L-leucinate, SUL) were synthesized and
      polymerized individually to form poly-SUS and poly-SUL. These surfactants were
      then copolymerized at various molar ratios to produce a variety of copolymerized
      surfactants (CoPSs), possessing both achiral (sulfate) and chiral (leucinate)
      head groups. The CoPSs, poly-SUS, poly-SUL, and sodium dodecyl sulfate were
      characterized using several analytical techniques. The aggregation numbers of the
      polymeric surfactants and the partial specific volumes were determined by the use
      of fluorescence quenching and density measurements, respectively. These polymeric
      surfactants were investigated as novel pseudostationary phases in micellar
      electrokinetic chromatography (MEKC) for the separation of chiral and achiral
      solutes. Solute hydrophobicity was found to have major influence on the MEKC
      retention of alkyl phenyl ketones. In contrast, hydrogen-bonding ability of
      benzodiazepines is the major factor that governs their retention, but
      hydrophobicity has an insignificant effect on MEKC retention of benzodiazepines.

PMID- 14679569
TI  - Chiral separation with ligand-exchange micellar electrokinetic chromatography
      using a D-penicillamine-copper(II) ternary complex as chiral selector.
AB  - D-Penicillamine is demonstrated for the first time as a chiral ligand for the
      enantioseparation of dansyl amino acids based on ligand-exchange micellar
      electrokinetic chromatography (LE-MEKC). Copper(II) was used as the central ion
      in the ternary complex. The effect of surfactant on the resolution was
      significant. A concentration of 20 mM sodium dodecyl sulfate (SDS) was shown to
      be necessary for the separation. Other important parameters, such as the
      concentration ratio of D-penicillamine (D-PEN) to Cu2+, the kind of metal central
      ion, the type and pH value of buffer, were also investigated. N-Acetyl-D
      penicillamine and L-valine (Val), with similar structure to D-penicillamine, were
      applied as their copper(II) complexes as chiral selector and the chiral
      recognition mechanism is briefly discussed. Under optimum experimental
      conditions, i.e., 20 mM NH4OAc, pH 6.5, a 2:1 concentration ratio of D
      penicillamine to Cu(II), 4 mM CuSO4 and 8 mM D-penicillamine, the chiral
      separation of eight pairs of different dansyl amino acid enantiomers was
      accomplished with resolution ranging from 1.1 to 5.9. When L-PEN was used instead
      of D-PEN, reversal of the migration order was observed.

PMID- 14679570
TI  - Characterization of surfactant and phospholipid vesicles for use as
      pseudostationary phases in electrokinetic chromatography.
AB  - The physical, electrophoretic and chromatographic properties (mean diameter,
      electroosmotic flow, electrophoretic mobility, elution range, efficiency,
      retention, and hydrophobic, shape, and chemical selectivity) of three surfactant
      vesicles and one phospholipid vesicle were investigated and compared to a
      conventional micellar pseudostationary phase comprised of sodium dodecyl sulfate
      (SDS). Chemical selectivity (solute-pseudostationary phase interactions) was
      discussed from the perspective of linear solvation energy relationship (LSER)
      analysis. Two of the surfactant vesicles were formulated from nonstoichiometric
      aqueous mixtures of oppositely charged, single-tailed surfactants, either
      cetyltrimethylammonium bromide (CTAB) and sodium octyl sulfate (SOS) in a 3:7
      mole ratio or octyltrimethylammonium bromide (OTAB) and SDS in a 7:3 mole ratio.
      The remaining surfactant vesicle was comprised solely of bis(2-ethylhexyl)sodium
      sulfosuccinate (AOT) in 10% v/v methanol, and the phospholipid vesicle consisted
      of 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine (POPC) and phosphatidyl serine
      (PS) in 8:2 mole ratio. The mean diameters of the vesicles were 76.3 nm (AOT),
      86.9 nm (CTAB/SOS), 90.1 nm (OTAB/SDS), and 108 nm (POPC/PS). Whereas the
      coefficient of electroosmotic flow (10(-4) cm2 V(-1) s(-1)) varied considerably
      (1.72 (OTAB/SDS), 3.77 (CTAB/SOS), 4.05 (AOT), 5.26 (POPC/PS), 5.31 (SDS)), the
      electrophoretic mobility was fairly consistent (-3.33 to -3.87 x 10(-4) cm2 V(-1)
      s(-1)), except for the OTAB/SDS vesicles (-1.68). This resulted in elution ranges
      that were slightly to significantly larger than that observed for SDS (3.12):
      3.85 (POPC/PS), 8.6 (CTAB/SOS), 10.1 (AOT), 15.2 (OTAB/SDS). Significant
      differences were also noted in the efficiency (using propiophenone) and
      hydrophobic selectivity; the plate counts were lower with the OTAB/SDS and
      POPC/PS vesicles than the other pseudostationary phases (< or = 75,000/m vs. >
      105,000/m), and the methylene selectivity was considerably higher with the
      CTAB/SOS and OTAB/SDS vesicles compared to the others (ca. 3.10 vs. < or = 2.6).
      In terms of shape selectivity, only the CTAB/SOS vesicles were able to separate
      all three positional isomers of nitrotoluene with near-baseline resolution.
      Finally, through LSER analysis, it was determined that the cohesiveness and
      hydrogen bond acidity of these pseudostationary phases have the greatest effect
      on solute retention and selectivity.

PMID- 14679571
TI  - Perfusive flow and intraparticle distribution of a neutral analyte in capillary
      electrochromatography.
AB  - The relevance and magnitude of an electroosmotic perfusion mechanism in
      electrochromatography is analyzed. To systemize our studies we first considered
      the transport of an electroneutral and nonadsorbing tracer. Based on the
      refractive index matching in a microfluidic setup containing fixed spherical
      porous particles, we conducted a quantitative analysis in real time of the spatio
      temporal distribution of fluorescent tracer molecules during their uptake by (and
      a release from) single particles using confocal laser scanning microscopy. Even
      under conditions of a significant electrical double layer overlap the
      intraparticle electroosmotic flow produces due to its unidirectional nature and
      in striking contrast to the symmetric (spherical) distributions typical for
      purely diffusive transport strongly asymmetric concentration profiles inside
      spherical particles as the locally charged pore liquid begins to respond to the
      externally applied electrical field. The profiles retain an axisymmetric nature,
      i.e., rotational symmetry with respect to the field direction. Results of our
      measurements could be successfully interpreted and further analyzed by a compact
      mathematical model. Intraparticle Peclet numbers of up to 150 have been realized
      and found to significantly enhance the mass transport on particle scale towards
      the convection-dominated regime when compared to a conventional (diffusion
      limited) kinetics.

PMID- 14679572
TI  - Partial filling technique in capillary electrophoresis for the separation of
      phenolic isomers with sulfonatocalix[4]arene as a selector.
AB  - p-Sulfonatocalix[4]arene was used as a selector in capillary electrophoresis to
      separate phenolic positional isomers. To avoid the detection interference caused
      by the high UV absorption of calixarene, the partial filling technique was
      applied. The operation variables, including buffer, separation voltage, the
      concentration of the selector and the plug length of the selector zone, were
      systematically optimized. The detection limits of mass were in the range of 0.07
      0.28 pg. Molecular modeling was used to explain the interaction between
      calixarene and phenolic isomers.

PMID- 14679573
TI  - Nonaqueous capillary electrophoretic separation of polyphenolic compounds in wine
      using coated capillaries at high pH in methanol.
AB  - Nonaqueous capillary electrophoretic separation of a group of flavonoids
      (quercetin, myricetin, catechin, epicatechin) and resveratrol in wine was
      investigated in methanol at high pH. Malonate background electrolyte (pH* 13.5,
      ionic strength I = 14.2 mmol/L) provided highly repeatable separations of the
      analytes. Tests of untreated and coated (poly(glycidylmethacrylate-co-N
      vinylpyrrolidone)) capillaries showed the analysis to be faster (6.5 min vs. 25
      min) and the repeatability better in the coated capillaries. The coating
      procedure was simple and highly repeatable and the coating was stable during 40
      45 runs. Determination of the last migrating peaks (epicatechin, resveratrol and
      catechin) was achieved merely by evaporating the wine samples and reconstituting
      the residue in methanol. For determination of the first migrating peaks
      (quercetin and myricetin) the samples were submitted to solid-phase extraction in
      C8 cartridges.

PMID- 14679574
TI  - Capillary zone electrophoresis with a dynamic double coating for analysis of
      carbohydrate-deficient transferrin in human serum: impact of resolution between
      disialo- and trisialotransferrin on reference limits.
AB  - Capillary electrophoresis with a dynamic double coating formed by charged
      polymeric reagents represents a very effective tool for the separation of iron
      saturated transferrin (Tf) isoforms and thus the determination of carbohydrate
      deficient transferrin (CDT) in human serum. The resolution between di- and
      trisialo-Tf is dependent on the applied voltage and capillary temperature. With a
      50 microm inside diameter (ID) capillary of about 60 cm total length mounted into
      the P/ACE MDQ, 28 kV and 40 degrees C, the resolution of the two Tf isoforms is
      shown to be between 1.0 and 1.4, whereas with reduced voltage and/or temperature,
      increased resolution at the expense of elongated run times is observed. Best data
      with complete resolution (Rs > or = 1.4) are obtained at 20 kV and 30 degrees C.
      For the determination of CDT in serum, incomplete separation of di- and trisialo
      Tf is demonstrated to have an impact on the reference limits. Analysis of the
      sera of 54 healthy individuals with no or moderate alcohol consumption and using
      valley-to-valley peak integration, the upper (lower) reference limits for CDT in
      relation to total Tf at the two power levels are 1.33 (0.52) and 1.57 (0.81)%,
      respectively, representing intervals that are significantly different (P <
      0.001). Furthermore, the reference intervals are shown to be strongly dependent
      on the peak integration approach used. Valley-to-valley peak integration should
      only be employed for conditions with complete resolution between disialo- and
      trisialo-Tf.

PMID- 14679575
TI  - Characterization of antithrombin III from human plasma by two-dimensional gel
      electrophoresis and capillary electrophoretic methods.
AB  - The isoforms distribution of the glycoprotein antithrombin III (ATIII) derived
      from human plasma was investigated by means of isoelectric focusing (IEF) in
      polyacrylamide gels with immobilized pH gradients (IPG) and two-dimensional gel
      electrophoresis (2-DE) as well as capillary electrophoretic methods. It turned
      out that the presence of high concentrations of chaotropics (urea, thiourea) and
      zwitterionic detergents (3-[(3-cholamidepropyl)dimethylammonio]-1
      propanesulfonate (CHAPS)) was decisive for attaining good resolution of the
      protein isoforms. Resolution by IPG-IEF was obtained with excellent
      reproducibility and pI differences down to 0.01 pH units could be distinguished.
      ATIII-alpha and ATIII-beta-fractions preseparated by heparin affinity
      chromatography showed an analogous but shifted spot pattern consisting each of
      one major and three minor isoforms. The main isoforms of ATIII-alpha and ATIII
      beta exhibit pI values of 5.18 and 5.32, respectively, both values determined in
      the presence of high concentrations of urea. The pI difference of 0.14 pH units
      correspond to the effect of two sialic acids absent in ATIII-beta. The formation
      and occurrence of ATIII dimers and trimers turned out to be dependent on the
      sample preparation. The results obtained by 2-DE were compared with those of
      capillary zone electrophoresis (CZE) and capillary IEF (CIEF). Quantitative
      analysis regarding the CZE separated isoforms of plasma derived ATIII yielded a
      content of about 70% ATIII-alpha main isoform and about 6.6% of ATIII-beta. The
      pI values of ATIII determined by CIEF with internal calibration were in fair
      agreement with the pI values of the main isoforms achieved with 2-DE.

PMID- 14679576
TI  - Proteomic analysis of pancreatic ductal carcinoma cells treated with 5-aza-2'
      deoxycytidine.
AB  - A pancreatic adenocarcinoma cell line (PaCa44), which contains, among other
      alterations, a methylated p16 promoter, was treated with a chemoterapeutic agent,
      5-aza-2'-deoxycytidine (DAC), in order to evaluate the effect of this drug on
      cell growth and protein expression. Cell proliferation was strongly inhibited by
      a 24 h DAC treatment and this inhibition lasted for at least 10 days. Master maps
      of control and treated PaCa44 cells were generated by analysis with the PDQuest
      software. The comparison between such maps showed up- and downregulation of 45
      polypeptide chains, of which 32 were downregulated and 13 upregulated, out of a
      total of 700 spots detected by a medium-sensitivity stain, micellar Coomassie
      Brilliant Blue. Fingerprinting by mass spectrometry analysis enabled the
      identification of 36 of these spots. Among the major changes in DAC-treated
      cells: cofilin and profilin 1 are silenced; coactosin, peptidyl-propyl cis-trans
      isomerase A and cystatin B are decreased by 22, 16- and 15-fold, respectively;
      stress-70 protein, superoxide dismutase and protein disulfide isomerase A3 are
      increased by 13-, 11-, and 5-fold, respectively. The significance of some of
      these major changes is discussed.

PMID- 14679580
TI  - Pendred syndrome and DFNB4-mutation screening of SLC26A4 by denaturing high
      performance liquid chromatography and the identification of eleven novel
      mutations.
AB  - Mutations in SLC26A4 cause Pendred syndrome, an autosomal-recessive disorder
      characterized by sensorineural deafness and goiter, and DFNB4, a type of
      autosomal recessive nonsyndromic deafness in which, by definition, affected
      persons do not have thyromegaly. The clinical diagnosis of these two conditions
      is difficult, making mutation screening of SLC26A4 a valuable test. Although
      screening can be accomplished in a variety of ways, all techniques are not
      equally accurate, timely or cost effective. We found single-strand conformational
      polymorphism analysis (SSCP) to be 63% effective in detecting mutations a panel
      of different SLC26A4 allele variants when compared to data from direct
      sequencing. Because direct sequencing can be time consuming and expensive,
      especially for a gene with 21 exons, we studied DHPLC as an alternative screening
      method. We found DHPLC as accurate and reliable as direct sequencing but to be
      more rapid and cost effective. In addition, we report 11 novel disease-causing
      allele variants of SLC26A4.

PMID- 14679581
TI  - Molecular cytogenetic analysis of complex chromosomal rearrangements in patients
      with mental retardation and congenital malformations: delineation of 7q21.11
      breakpoints.
AB  - Constitutional de novo complex chromosomal rearrangements (CCRs) are a rare
      finding in patients with mild to severe mental retardation. CCRs pose a challenge
      to the clinical cytogeneticist: generally CCRs are assumed to be the cause of the
      observed phenotypic abnormalities, but the complex nature of these chromosomal
      changes often hamper the accurate delineation of the chromosomal breakpoints and
      the identification of possible imbalances. In a first step towards a more
      detailed molecular cytogenetic characterization of CCRs, we studied four de novo
      CCRs using multicolor fluorescent in situ hybridization (M-FISH), comparative
      genomic hybridization (CGH), and FISH with region specific probes. These methods
      allowed a more refined characterization of the breakpoints in three of the four
      CCRs. The occurrence of 7q breakpoints in three out of these four CCRs and in 30%
      of reported CCRs suggested preferential involvement of this chromosomal region in
      the formation of CCRs. Further analysis of these 7q breakpoints revealed a 2 Mb
      deletion at 7q21.11 in one patient and involvement of the same region in a
      cryptic insertion in a second patient. This particular region contains at least 5
      candidate genes for mental retardation. The other patient had a breakpoint more
      proximal to this region. The present data together with these from the literature
      provide evidence that a region within 7q21.11 may be prone to breakage and
      formation of CCRs.

PMID- 14679582
TI  - A genomic scan for habitual smoking in families of alcoholics: common and
      specific genetic factors in substance dependence.
AB  - Smoking is a highly heritable, addictive disorder that commonly co-occurs with
      alcohol dependence. The purpose of this study is to perform a genomic screen for
      habitual smoking and comorbid habitual smoking and alcohol dependence in families
      from the Collaborative Study on the Genetics of Alcoholism (COGA). Subjects were
      assessed using the Semi-Structured Assessment for the Genetics of Alcoholism
      (SSAGA) to evaluate alcohol dependence and habitual smoking (smoking one pack per
      day or more for at least 6 months). Sixty seven multi-generational families with
      154 independent sibling pairs affected with habitual smoking were genotyped in a
      screening sample. Analyses on 79 multi-generational families with 173 independent
      sibling pairs were repeated in a replication sample. Sibpair analyses were
      performed using ASPEX. Four chromosomal regions in the screening sample had
      increased allele sharing among sibling pairs for habitual smoking with a LOD
      score greater than 1 (chromosomes 5, 9, 11, and 21). The highest LOD score was on
      chromosome 9 (LOD = 2.02; allele sharing 58.9%). Four chromosomal regions also
      had modest evidence for linkage to the comorbid phenotype habitual smoking and
      alcohol dependence (chromosomes 1, 2, 11, 15); and the strongest finding was on
      chromosome 2 (LOD = 3.30; allele sharing 69.1%). Previously identified areas
      (chromosomes 1 and 7) implicated in the development of alcohol dependence in this
      same data set did not provide evidence for linkage to habitual smoking in the
      screening sample. In the replication data set, there continued to be increased
      allele sharing near peaks identified in the screening sample on chromosomes 2 and
      9, but the results were modest. An area on chromosome 7, approximately 60 cM from
      a location previously identified in linkage analysis with alcohol dependence, had
      increased allele sharing for the comorbid habitual smoking and alcohol
      dependence. These data provide evidence of specific genetic regions involved in
      the development of habitual smoking and not alcohol dependence. Conversely,
      genetic regions that influence the development of alcohol dependence do not
      appear to contribute to the development of habitual smoking. Finally, there is
      also evidence of an area on chromosome 2 that may reflect a common genetic
      vulnerability locus to both habitual smoking and alcohol dependence.

PMID- 14679583
TI  - Brittle cornea syndrome and its delineation from the kyphoscoliotic type of
      Ehlers-Danlos syndrome (EDS VI): report on 23 patients and review of the
      literature.
AB  - The brittle cornea syndrome (BCS) is a generalized connective tissue disorder
      characterized by corneal rupture following only minor trauma, keratoconus or
      keratoglobus, blue sclerae, hyperelasticity of the skin without excessive
      fragility, and hypermobility of the joints. It is inherited as an autosomal
      recessive trait but the underlying genetic defect remains undetermined. We
      present 23 patients (11 male) from 13 nuclear families followed at the King
      Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia, aged 3-28 years at last
      follow-up. A total of 28 events of corneal rupture were noted in 17 patients
      (eight male), among whom nine had had bilateral ruptures, and eight had had
      unilateral ruptures (four of the right cornea), while two had experienced re
      rupture 2 and 4 years, respectively, after surgery; six patients (aged 3-21
      years) had had no ruptures. We describe the natural history of our cases and
      discuss them together with those others reported in the literature. Because of
      similarities between the BCS and the kyphoscoliotic type of the Ehlers-Danlos
      syndrome (EDS VI), both disorders tend to have been confounded. Here, we show
      that all of our BCS patients tested in this regard had biochemical findings
      reflective of normal activity of lysyl hydroxylase, characteristically deficient
      in EDS VI, such as normal urinary total pyridinoline ratios and/or normal
      electrophoretic migration of collagen chains produced by dermal fibroblasts. The
      BCS is, therefore, an entity distinct from the kyphoscoliotic type of EDS, which
      has a much poorer prognosis.

PMID- 14679584
TI  - DEB test for Fanconi anemia detection in patients with atypical phenotypes.
AB  - Pancytopenia, hyperpigmentation, small stature, congenital abnormalities, and
      predisposition to neoplasia characterize Fanconi anemia (FA). The clinical
      phenotype is extremely variable, therefore the diagnosis is frequently delayed
      until the pancytopenia appears, making diagnosis difficult on the basis of
      clinical manifestations alone. Hypersensitivity of FA cells to the clastogenic
      effect of diepoxybutane (DEB) provides a unique marker for the diagnosis before
      the beginning of hematological manifestations. Our aim in this study was to
      detect FA in children with atypical manifestations to define which conditions
      should be routinely included in the DEB test screening. We performed the
      chromosomal breakage test in 34 patients with probable FA and 83 patients with
      clinical conditions that could suggest FA, but are not usually screened by the
      DEB test: 20 patients with aplastic anemia, 20 patients with VACTERL association,
      20 with radial ray abnormalities, 7 with tracheo-esophageal fistulae, 12 with
      anal atresia, and 4 with myelodysplastic syndrome. We found 18 DEB-positive
      patients: 12 were in the group of probable FA and 6 in the other groups. Among
      the last ones: three were included because of aplastic anemia, without any other
      sign of FA, however when re-examined, other anomalies were detected. The third
      patient had anal atresia, renal hypoplasia, pre-axial polydactyly, and normal
      blood cell counts and was diagnosed as having VACTERL association. The other two
      patients lacking physical or hematological signs were identified among the group
      of radial ray abnormalities. Thus, our results highlight the need to increase the
      number of abnormalities indicating need for a DEB test. Delay in the diagnosis of
      FA may have serious consequences for the patients and their family members.

PMID- 14679585
TI  - Genetic variants in ZIC1, ZIC2, and ZIC3 are not major risk factors for neural
      tube defects in humans.
AB  - Neural tube defects (NTD) are congenital malformations arising from incomplete
      neural tube closure during early embryogenesis. Most NTD in humans show complex
      inheritance patterns, with both genetic and environmental factors involved in the
      etiology of this malformation. More than 120 mouse models for human NTD exist.
      NTD have been observed in mice deficient for the Zic family genes, Zic1, Zic2,
      and Zic3. We performed mutation analysis in the human orthologs of these genes
      using DNA material from a large panel of NTD patients. In ZIC2 we identified a
      deletion of one codon that encodes an alanine residue located in the amino
      terminal alanine stretch of the protein. The deletion was present in one patient,
      but not in 364 controls. That may suggest a role-albeit small-of this variant in
      the etiology of NTD in humans. Transmission disequilibrium testing of a frequent
      polymorphism in the ZIC2 gene (1059C > T, H353H) in parent-spina bifida aperta
      child triads showed no association with NTD. One silent polymorphism (858G > A,
      V286V) of unknown significance was identified in ZIC3. Neither mutations nor
      polymorphisms were found in the coding region or flanking sequences of ZIC1. Our
      data indicate that ZIC1, ZIC2, and ZIC3 are not major risk factors for NTD in
      humans.

PMID- 14679586
TI  - Desbuquois dysplasia, a reevaluation with abnormal and "normal" hands:
      radiographic manifestations.
AB  - Radiological features of 35 patients with the diagnosis of Desbuquois dysplasia
      were analyzed. The diagnosis of Desbuquois dysplasia was based on the association
      of specific facial alterations, markedly short stature of prenatal onset, joint
      laxity, "Swedish key" appearance of the proximal femur, and advanced carpal and
      tarsal bone age. Patients were divided into two groups, depending on whether or
      not typical hands with an extra ossification center distal to the second
      metacarpal and/or a delta phalanx of the thumb were present (group 1, 46%) or
      absent (group 2, 54%). In this study, beside the "Swedish key" appearance of the
      proximal femur and advanced carpal and tarsal ossification, we were able to
      define three additional major radiographic criteria for the diagnosis of
      Desbuquois dysplasia, including flat acetabular roof, elevated greater
      trochanter, and proximal fibular overgrowth. Other manifestations included wide
      metaphyses, flat epiphyses, coxa valga, coronal and sagittal clefts of the
      vertebrae, wide anterior rib portions, medial deviation of the foot, and enlarged
      first metatarsal. We conclude that characteristic hand abnormalities are not
      mandatory for the diagnosis of Desbuquois dysplasia.

PMID- 14679587
TI  - Long-term outcome in Desbuquois dysplasia: a follow-up in four adult patients.
AB  - Desbuquois dysplasia is a rare chondrodysplasia characterized by short stature,
      joint laxity, and specific radiographic findings. We report the natural history
      of four patients (three boys and one girl) with Desbuquois dysplasia ages 16-22
      years. The mean height in adulthood was 114 cm (-8.5 SD) with progressive
      deceleration of the growth curve from birth (-4 SD) to adulthood. Obesity was
      noted consistently and facial abnormalities were still present but less obvious
      than in childhood. Three of four patients had mental retardation of varying
      degree. Hyperlaxity was persistent but limited motion of various joints was also
      noted. Orthopedic complications included coxa vara or valga (3/4), scoliosis
      (3/4), marked lordosis (3/4), and ambulatory difficulties (3/4). Surgical
      treatment was necessary for all four patients, involving large joints, spine and
      hands. Other complications included acute open-angle glaucoma secondary to a
      congenital malformation of the angle in one case. In addition to consistent
      radiological findings, elevated greater trochanter, generalized osteoporosis
      especially of the spine, scoliosis and/or lordosis, wide metaphyses, flat
      epiphyses, and coxa vara or valga were part of the natural history of the
      disorder. Our study emphasizes the care of older patients with Desbuquois
      dysplasia.

PMID- 14679588
TI  - Metaphyseal chondrodysplasia with cone-shaped epiphyses: a specific form
      involving the lower limbs.
AB  - Three unrelated patients affected by a characteristic metaphyseal
      chondrodysplasia with cup-shaped metaphyses of the knees are described. Lower
      femoral and upper tibial cone-shaped epiphyses were embedded in the metaphyses.
      Main clinical features are short stature, shortening of the lower limbs,
      limitation of knee extension, and normal hands length. Radiographs of skull,
      spine, and hands showed no abnormality. This particular appearance of the knees
      has been seldom described in acquired disease such as repeated injuries,
      meningococcemia, scurvy, and hypervitaminosis A. Metaphyseal dysplasias with
      these distinctive radiological findings of the knees are uncommon. Differential
      diagnosis includes trichoscyphodysplasia and acroscyphodysplasia among others.
      Two other cases reported by Kozlowski showed the most similarities to our three
      cases and defined a new form of metaphyseal dysplasia with specific lower limbs
      involvement and cup-shaped metaphyses.

PMID- 14679589
TI  - A severe autosomal-dominant periodic inflammatory disorder with renal AA
      amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a
      Spanish kindred: an unusual familial Mediterranean fever phenotype or another
      MEFV-associated periodic inflammatory disorder?
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disease
      characterized by recurring short attacks of fever and serositis. Secondary AA
      amyloidosis is the worst complication of the disease and often determines the
      prognosis. The MEFV gene, on chromosome 16p13.3, is responsible for the disease
      and around 30 mutations have been reported to date. Colchicine is the standard
      FMF treatment today, and prevents both attacks and amyloid deposition in 95% of
      patients. Here we describe a three-generation Spanish kindred with five family
      members affected by a severe periodic inflammatory disorder associated with renal
      AA amyloidosis and colchicine unresponsiveness. Clinical diagnosis of definite
      FMF disease was made based on the Tel-Hashomer criteria set. Genetic analyses
      revealed that all subjects were heterozygous for the new H478Y MEFV variant,
      segregating with the disease. In addition, mutations in the TNFRSF1A and
      CIAS1/PYPAF1/NALP3 genes, related to the dominantly inherited autoinflammatory
      periodic syndromes, were ruled out. However, the dominant inheritance of the
      disease, the long fever episodes with a predominant joint involvement, and the
      resistance to colchicine in these patients raise the question of whether the
      periodic syndrome seen in this kindred is a true FMF disease with unusual
      manifestations or rather another MEFV-associated periodic syndrome. We conclude
      that the new H478Y MEFV mutation is the dominant pathological variant causing the
      inflammatory periodic syndrome in this kindred and that full-length analyses of
      the MEFV gene are needed to obtain an adequate diagnosis of patients with
      clinical suspicion of a hereditary periodic fever syndrome, especially those from
      non-ancestral populations.

PMID- 14679590
TI  - Brothers with Chudley-McCullough syndrome: sensorineural deafness, agenesis of
      the corpus callosum, and other structural brain abnormalities.
AB  - We describe two brothers with Chudley-McCullough syndrome who are 5 and 17 years
      old. They were born to healthy consanguineous parents of Pakistani descent. They
      had severe sensorineural deafness and neuroimaging showed corpus callosum
      agenesis and other structural brain abnormalities. The Chudley-McCullough
      syndrome is an autosomal recessive disorder, first described by Chudley et al.
      [1997: Am J Med Genet 68:350-356]. The original description of the syndrome
      includes hydrocephalus due to obstruction of the foramen of Monro and early-onset
      severe to profound sensorineural deafness. We review the findings in the two
      patients we describe, four children reported in the literature and two patients
      reported by Hendriks et al. [1999: Am J Med Genet 86:183-186] with sensorineural
      deafness, corpus callosum agenesis, and interhemispheric cysts, who may well have
      Chudley-McCullough syndrome. All patients had sensorineural deafness. The
      neuroimagings of all eight patients showed colpocephaly, which is most likely
      caused by corpus callosum agenesis. Three patients had other structural brain
      abnormalities: cortical dysplasia and gray matter heterotopia. We suggest a
      revision of the clinical description since the most likely basic developmental
      defect is corpus callosum agenesis and not foramen of Monro obstruction.

PMID- 14679591
TI  - Isochromosome 22 in trisomy 22 mosaic with five cell lines.
AB  - This report describes a full-term male infant with trisomy 22 due to an
      isochromosome 22. Prenatal diagnosis with amniotic fluid showed two cell lines,
      one with an isochromosome 22 and the other with a deleted isochromosome 22.
      Subsequent cytogenetic analyses of cord blood, umbilical cord tissue, and
      placenta revealed additional cell lines. A normal cell line was found in
      umbilical cord tissue and two of three placental sites. The newborn had numerous
      dysmorphic features and died within 48 hrs of birth.

PMID- 14679593
TI  - Different phenotypic expression in monozygotic twins with Huntington disease.
AB  - Monozygotic (MZ), 46-year-old, male twins, carrying the same Huntington disease
      (HD) mutation, presented with a different clinical course. In one of the twins,
      the disease process started at the age of 32 years with chorea, dysarthria, and a
      depressed mood. Over 14 years, the disease progressed to total functional
      dependence. The second twin presented at age 35 with gait disturbances. His
      behavior became aggressive with an obsessive pattern, whereas the motor features
      included hypokinesia, rigidity, gait unsteadiness, and dysarthria. This is the
      first report of genetic identity associated with different age of disease onset
      as well as a different motor and behavioral phenotype. Postzygotic events are a
      likely explanation for the observed differences of phenotype in these genetically
      identical twins.

PMID- 14679592
TI  - Prenatal diagnosis of fetal trisomy 6 mosaicism and phenotype of the affected
      newborn.
AB  - The first case of a fetal trisomy 6 mosaicism proven at 25 weeks of gestation by
      analysis of fetal urine cells is described. Chromosomal analysis was indicated by
      an ultrasonographically diagnosed heart defect at 21 weeks of gestation. The
      chromosomal aberration was detected in amniotic fluid cells while fetal blood
      cells showed a normal chromosome set. At term a boy with normal growth parameter
      was born. In addition to the expected heart defect, malformations of hands and
      feet were present.

PMID- 14679594
TI  - Molecular cytogenetic characterization of a recombinant chromosome
      rec(22)dup(22q)inv(22)(p13q12.2).
AB  - Pericentric inversions occur at a frequency of 0.12-0.7% in humans. However,
      pericentric inversions of chromosome 22 appear to be common, especially in
      patients originating from the Guadalajara region of Mexico. Here, we report a
      seventh case of a pericentric inversion of chromosome 22, the resulting
      recombinant chromosome, and describe the phenotypic features associated with such
      a recombinant chromosome. It is interesting that five of the seven patients with
      inv(22) come from Mexico, and four of the five patients from the Guadalajara
      region.

PMID- 14679595
TI  - Double trisomy.

PMID- 14679596
TI  - Screening for microdeletions of the X-chromosome in non-specific mental
      retardation.

PMID- 14679597
TI  - Facial phenotype allows diagnosis of Mowat-Wilson syndrome in the absence of
      Hirschsprung disease.

PMID- 14679598
TI  - Reconstructing haplotypes in pedigrees: importance of parental information.

PMID- 14679599
TI  - Federal tort reform initiatives. Congressman James C. Greenwood discusses jackpot
      justice. Interview by Patricia A. Costante, Robert B. Goley, Janet Spicer Puro.

PMID- 14679600
TI  - Out-of-hospital do-not-resuscitate (DNR) orders. The New Jersey protocol.

PMID- 14679601
TI  - Sexual harassment complaints. Mandate from the Board of Medical Examiners.

PMID- 14679602
TI  - Dangerous busy minds.

PMID- 14679603
TI  - Post mortems on post mortems.

PMID- 14679604
TI  - Utility of ST segment depression in lead AVL in the diagnosis of right
      ventricular infarction.
AB  - We performed twelve lead electrocardiograms(ECG) and right precordial leads on
      twenty-two consecutive patients with first inferior wall acute myocardial
      infarction (MI) diagnosed by classical Q waves and elevation of cardiac enzymes.
      The presence of right ventricular MI was established by either technetium 99 (TC
      99) pyrophosphate scanning or 2-dimensional (2-D) echocardiography by observers
      unrelated to the study and not aware of the electrocardiographic findings. In
      patients with established right ventricular MI (n = 15/22), ST segment elevation
      > or = 0.1 mV in lead V4R placed in the right precordial lead position had 91%
      (10/11) sensitivity in diagnosing right ventricular MI. ST segment depression in
      lead AVL > or = 0.1 mV had 100% sensitivity in diagnosing right ventricular MI
      (15/15). In the seven patients without right ventricular infarction, the absence
      of ST segment elevation in lead V4R had 100% specificity (7/7), while the absence
      of ST segment depression in lead AVL had 57% specificity (4/7) in excluding right
      ventricular infarction. The data indicate that in the presence of inferior wall
      MI, ST segment depression in lead AVL is a sensitive, but not very specific sign
      of right ventricular MI. Therefore, its presence in patients with inferior wall
      MI should lead to further investigations to diagnose or exclude right ventricular
      MI.

PMID- 14679605
TI  - Shaping health care policy and priorities in tough fiscal times.

PMID- 14679606
TI  - Response to Raymond Cantor's Newswatch piece in your July-August 2003 issue.

PMID- 14679607
TI  - Opinion: New Jersey is still the world's cure corridor.

PMID- 14679608
TI  - Military nurses answering the call to serve. Interview by Sandra Konrad.

PMID- 14679609
TI  - RN leadership: the key to a healthy workplace.

PMID- 14679612
TI  - Retired nurses' oral histories.

PMID- 14679613
TI  - Women in the military.

PMID- 14679614
TI  - DRG validation advisory committee completes guidelines.

PMID- 14679615
TI  - Grief, loss and bereavement.

PMID- 14679617
TI  - Transition planning and retirement.

PMID- 14679616
TI  - Can enamel serve as a useful clinical marker of childhood stress?

PMID- 14679618
TI  - What do you do with your dental office when you no longer want to practice?

PMID- 14679619
TI  - My life.... bonsai ... recreation and relaxation.

PMID- 14679620
TI  - Office design & construction.

PMID- 14679621
TI  - The agony & ecstacy of building a new office.

PMID- 14679622
TI  - [Anti-hepatitis b prevention. Consensus conference reviews the necessity of
      vaccination].

PMID- 14679624
TI  - [Community health nursing: a little known public health mission].

PMID- 14679625
TI  - [Affection and learning. The pleasure of or the duty in the art of respecting
      oneself and the others].

PMID- 14679626
TI  - [Degree of patient satisfaction regarding the reception given by emergency
      service nurses].
AB  - Humanizing in hospitals begins with the patients' reception. Although this
      "function" should be considered as the duty of every person who works in
      Hospital, it is fundamental to be assumed as a nursing service, since we are the
      professional sector which spends more time with the patient. However, the
      reception may have positive or negative effects on the patient's recovery and on
      the Health Unit's image. Thus, and having the mission of optimizing the quality
      of health care, mainly as far as reception is concerned, with this study came
      out, through which we intend to analyse the patient's level of satisfaction as
      for the reception offered by the nurse in the Emergency Service of Hospital Sao
      Marcos de Braga. It is a study of a descriptive and exploratory nature, within a
      quantitative approach. To carry out this empirical study, we considered as target
      population the patients who needed the Emergency Service in the period between
      January and March of 2002, both male and female (about 50% of each), 50% of rural
      patients and 50% of urban patients, between the ages of 18 and 65 who stayed in
      this service from 3 to 12 hours. A random and representative selection of
      patients was taken, based on the criteria previously mentioned. We obtained a
      sample of 1440 patients through a random selection of 5 patients in the morning
      shift, 6 patients in the afternoon shift and 5 patients in the night shift,
      during the period in which the study was carried out. This study was carried out
      without the presence of the participants in the survey.

PMID- 14679627
TI  - [Pregnancy and drug dependence in adolescence: an ethical perspective].

PMID- 14679628
TI  - [Tell the world what you do].

PMID- 14679629
TI  - [Nursing care for the patient treated with hip arthroplasty].

PMID- 14679631
TI  - [Nursing care of patients with allogeneic stem cell transplantation: as much
      everyday routine as possible].

PMID- 14679632
TI  - [Interdisciplinary collaboration in hematologic oncology: the end of
      uncertainty].

PMID- 14679633
TI  - [Anemia and neutropenia in oncologic patients: modern growth factors simplify
      therapy].

PMID- 14679634
TI  - [Living with a hematologic-oncologic illness: information from person to person
      gives strength].

PMID- 14679635
TI  - [Nursing concerns in blood transfusions: chief responsibility: monitoring].

PMID- 14679636
TI  - [Home pediatric palliative medicine: facilitating good-byes at home].

PMID- 14679637
TI  - [Nursing care of the mouth in hematologic-oncologic illnesses: the guideline is
      the patient].

PMID- 14679638
TI  - [Evidence-based nursing in stomatitis: it may still be researched].

PMID- 14679639
TI  - [East-West educational dialogue in nursing: "Decisive are the heads" (interview
      by Katrin Balzer)].

PMID- 14679640
TI  - [FITT (Continuing education-Information-Training-Transfer) communication
      training: so that relationships are in tune].

PMID- 14679641
TI  - [Blood transfusions in Jehovah's Witnesses: when belief threatens life].

PMID- 14679642
TI  - [Gray zone in patient self-determination: probing the patient autonomy].

PMID- 14679643
TI  - [From case to case: invisible danger].

PMID- 14679644
TI  - [A year of integrated nursing education--the Stuttgart model: from pieces comes
      the whole].

PMID- 14679645
TI  - [Wound management, 11--Preoperative hair removal: what is left of a ritual].

PMID- 14679647
TI  - [QOL questionnaire for allergic rhinitis].

PMID- 14679646
TI  - [Hospice care in the USA].

PMID- 14679648
TI  - [Standard questionnaire for QOL of Japanese patients with allergic rhinitis].

PMID- 14679649
TI  - [QOL questionnaire for patients with perennial allergic rhinitis].

PMID- 14679650
TI  - [Preparation of Japanese versions of rinoconjunctivitis quality of life
      questionnaire (RQLQ) and work productivity and activity impairment questionnaire
      (WPAI-AS)].

PMID- 14679651
TI  - Squeeze on agencies.

PMID- 14679652
TI  - Continental drift.

PMID- 14679653
TI  - Ever ready.

PMID- 14679654
TI  - In the line of fire.

PMID- 14679655
TI  - Hurt feelings.

PMID- 14679656
TI  - Existential pain.

PMID- 14679657
TI  - Critical companionship. Part 2: Using the framework.
AB  - Part 1 presented the critical companionship framework for facilitating
      experiential learning, with exemplars of expertise. The development and testing
      of the framework were outlined. In Part 2, we show the framework being used by
      new critical companions, without educational backgrounds or previous facilitation
      of learning experience. The reflective accounts of the critical companions not
      only show how they analysed their work using the framework, but also reveal that
      these early experiences helped those they were facilitating to unravel their
      practice and look critically at how they, and others, practise. Some accounts
      hint at the outcomes for patients and relatives and show how critical
      companionship became integrated with leadership roles. We conclude that the
      framework can be useful in helping new critical companions to acquire effective
      critical companionship skills. In addition, we tentatively suggest that the
      development of expertise, as demonstrated in Part 1, is likely to take at least
      five years, unless the individual is already a skilled facilitator.

PMID- 14679658
TI  - Immunisation and the law: compulsion or parental choice?
AB  - A debate has been developing in Nursing Standard on the issue of childhood
      immunizations. This article adds to the discussion by considering the likelihood
      of legislation being introduced to make immunisation compulsory in the UK. It
      also discusses how the courts approach an application for childhood vaccination
      against the wishes of a parent and the implications for nursing practice of that
      approach.

PMID- 14679659
TI  - Promoting independence: the nurse as coach.
AB  - The government's modernization agenda strives to place the patient at the centre
      of healthcare services. Coaching techniques can be used to develop the skills of
      both patients and nurses. This article discusses the use of a coaching model to
      help patients make informed choices and take ownership of their health, while
      receiving healthcare support.

PMID- 14679660
TI  - Care of dying patients.
AB  - This article provides an overview of the care required by patients in the last 48
      72 hours of life, as well as the support required by carers.

PMID- 14679661
TI  - Diversity drive.

PMID- 14679662
TI  - The effect of dietary supplementation with calcium salts on skeletal calcium in
      suckling rats.
AB  - This study aimed at identifying a calcium compound which could serve as an
      effective and safe dietary supplement in suckling rats over the period of intense
      growth and development. The main objective was to assess the effect of additional
      calcium intake on skeletal calcium in suckling pups. Suckling Wistar rats were
      fed using a pipettor with one of the following calcium salts from day 6 to 14
      after the birth: gluconate, hydrogenphosphate, carbonate (each suspended in cow's
      milk), or chloride (in demineralized water). Control rats received only cow's
      milk. Calcium in the carcass (body without organs and skin) was analysed by
      atomic absorption spectrometry. The only effective dietary supplement that
      produced no risk for the suckling pups' growth was calcium hydrogenphosphate in
      cow's milk in the total amount of 340 mg. That dose increased the daily calcium
      intake 3 to 4 times compared to non-supplemented controls, increasing carcass
      calcium content by about 16 per cent. Other calcium compounds were either
      inefficient (carbonate) or had adverse effects on pups' growth (chloride and
      gluconate).

PMID- 14679663
TI  - Tobacco smoking in hotel workers and the necessity to promote non-smoking policy
      at the workplace.
AB  - This investigation aimed at evaluating the prevalence of active smokers in hotel
      workers to underline the need for a non-smoking campaign at the workplace. Data
      on smoking habit were collected in a questionnaire which included 398 subjects of
      whom 170 were men and 228 women aged in average 29 and 35 years, respectively.
      Seventy-six men and 134 women declared themselves regular tobacco smokers. In
      average, they started to smoke at the age of 17 and 18, respectively and had been
      smoking for 21 and 16 years, respectively. Although the number of smokers was
      high, it is encouraging that 29% of men and of 51% women tried and did not
      succeed in quitting smoking, whereas 30% of men and 12% of women did quit
      smoking. The authors advocate reducing tobacco use and controlling environmental
      tobacco smoke exposure at the workplace, which should include a non-smoking
      company policy, implementation of smoking cessation programmes, social support
      programmes, trade union support, as well as the assistance of health
      professionals during regular check-ups.

PMID- 14679664
TI  - [Lead exposure in highway toll-booth workers].
AB  - Biomarkers of lead exposure (blood lead, BPb) and effect (erythrocyte
      protoporhyrin, EP, and activity of delta-aminolevulinic acid dehydratase, ALAD)
      were measured in 68 male toll-booth operators (aged 22-60 years) on the Zagreb
      Karlovac motorway. Average values (arithmetic mean +/- standard deviation) were:
      61.8 +/- 29.3 micrograms/L for BPb, 0.70 +/- 0.20 mumol/L erythrocytes for EP,
      and 50.6 +/- 9.8 U/L erythrocytes for ALAD. All were within the normal range
      determined for general population (BPb < 150 micrograms/L, EP < 1.62 mumol/L
      erythrocytes, and ALAD > 35 U/L erythrocytes). A significant positive correlation
      was found between BPb and EP (r = 0.367, P < 0.01) and an inverse correlation
      between BPb and ALAD (r = -0.271, P < 0.05) and for EP and ALAD (r = -0.381, P <
      0.01). Significant correlations were found between BPb or ALAD and smoking index
      (r = 0.486, P < 0.01, and r = -0.322, P < 0.01, respectively), whereas BPb also
      significantly correlated with blood gamma-glutamyl transferase (GGT) activity,
      which may indicate hepatotoxic effect of alcohol consumption (r = 0.334, P <
      0.01). Among standard spirometric tests, BPb inversely correlated with FEV1 (r = 
      0.251, P < 0.05) and Tiffenau index (r = -0.280, P < 0.05), whereas ALAD
      positively correlated with FEF75-85 (r = 0.261, P < 0.05) and Tiffenau index (r =
      0.314, P < 0.01). Among standard hematologic tests, BPb positively correlated
      with MCV (r = 0.282, P < 0.05), EP inversely correlated with erythrocyte count (r
      = -0.253, P < 0.05), and ALAD positively correlated with MCHC (r = 0.306, P <
      0.05) and inversely with MCV (r = -0.250, P < 0.05). Although PbB values in these
      workers are within occupational exposure limits, they are higher than in
      corresponding occupations in developed countries. This may be explained by
      greater exposure to lead in ambient air, tobacco (through mainstream and
      sidestream smoking) and alcohol in this population.

PMID- 14679665
TI  - [Disorders of color vision].
AB  - This review gives a summary of all colour vision disorders (dyschromatopsias) and
      diagnostic methods and tests. Colour vision is inadequately treated in current
      literature with regard to the choice of diagnostic methods and the interpretation
      of results for a single disorder, which contributes to wrong dyschromatopsia
      diagnosing seen every day in specialist practice. Examination for colour
      disorders is usually outpatient and is carried out by ophthalmology or neurology
      departments or occupational health services under the supervision of an
      ophthalmologist to prevent misinterpretation of results and wrong occupational
      choices. The problem is very serious, and proper education should be able to
      provide guidelines for correct and early diagnosis of dyschromatopsia. As the
      examination is not well defined, it is very important to set unique criteria in
      diagnosing any single colour vision disorder.

PMID- 14679666
TI  - Public health preparedness for chemical incidents in Europe.
AB  - In response to the attack of 11 September 2001 on the USA, World Health
      Organization (WHO), Regional Office for Europe took immediate steps in order to
      be able to assist countries in case of a terrorist attack. Among other things,
      WHO organised a series of different consultations with international
      organisations, government representatives and experts in order to assess the
      state of preparedness at the national and international levels, to identify the
      main problems and to make recommendations. The problems were addressed in the
      context of possible public health consequences, regardless of whether such an
      incident derived from a deliberate act or a naturally occurring event. This
      overview gives a brief account of presentation made at the European Union "First
      Civil Protection Forum", which was held in Brussels in November 2002, and which
      served as a basis for defining the EU priorities and actions to make Europe a
      safer place to live.

PMID- 14679667
TI  - [The tryptophan depletion challenge: a review of methodology and results].
AB  - INTRODUCTION: This paper focuses on the methodology and behavioural results of
      the tryptophan depletion challenge. METHODS: A Medline search (1985-2002) using
      the keywords 'tryptophan depletion' and 'mood' has been performed. RESULTS: Rapid
      depletion is obtained by morning intake under fasting condition of a tryptophan
      free amino-acid mixture. Subjects with a family history of mood disorders and
      depressed patients receiving serotoninergic drugs demonstrate a mood-lowering
      effect. However, these effects are limited or absent in normal volunteers and
      naive depressed patients. CONCLUSION: The tryptophan depletion challenge has
      largely contributed to the understanding of the physiopathology of depression.
      However, the mood response to acute tryptophan depletion challenge in healthy
      volunteers is not as sensitive as a 'depression model'.

PMID- 14679668
TI  - [Evaluation of drug therapy knowledge in liver transplant patients after pharmacy
      counseling].
AB  - The analysis of the literature demonstrated that pharmacy counselling influenced
      patient outcome after transplantation. This was the reason we established
      pharmacy consultation in 1999. The aim of this study was to determine patient
      knowledge before and after pharmacy counselling. Twenty-nine patients were
      questioned about the identification, role and dosage of prescribed drugs. The
      mean duration of pharmacy counselling was 54 minutes. Before pharmacy
      consultation, the knowledge score was 53.7%. Afterwards, the mean score value
      reached 75% and seven patients had a score of 100%. The anti-rejection therapy
      was understood by 93% of patients. However, the associated drugs were poorly
      known: less than 15% of patients initially knew about the purpose of the
      antimicrobial agent, compared with 50-60% after counselling. During counselling,
      two women were identified as regularly using St John's Wort and were informed
      that this herbal medicine can endanger the success of organ transplantation. Five
      patients or family members called the pharmacist to obtain additional
      information. Among these, two medication errors, both with corticosteroid drugs,
      were reported by family members of patients of foreign origin who had difficulty
      in understanding and speaking French. Pharmacy counselling improved patient
      knowledge about therapy after transplantation.

PMID- 14679669
TI  - The effect of inhaled corticosteroids on the urinary calcium to creatinine ratio
      in childhood asthma.
AB  - BACKGROUND: The use of inhaled corticosteroids (ICS) via spacers in childhood
      asthma is increasing. However, concern has been raised about its long-term
      impact. Hypercalciuria is a known adverse effect of treatment with systemic
      corticosteroids. The urinary calcium to creatinine ratio (UCa:Cr) is a simple,
      reliable and non-invasive tool for evaluation of hypercalciuria. AIM: To
      determine whether ICS can induce hypercalciuria in children with asthma. SETTING:
      Outpatient clinic in a referral hospital. METHODS: The UCa:Cr was determined in
      25 children aged 3-6 years with mild-to-moderate persistent asthma before and
      after a 2-month course of inhaled budesonide 400 micrograms/day via an
      aerochamber. Children who had received oral corticosteroids, diuretics,
      antibiotics or theophylline were excluded. STATISTICS: Paired Student's t-test
      and Fisher's exact test. RESULTS: The mean UCa:Cr was similar in the children
      with asthma before and after 2 months' administration of budesonide (0.10 +/-
      0.10 and 0.11 +/- 0.08, respectively; p = 0.601). The numbers of hypercalciuric
      children were two and five, respectively (p = 0.417). In 68% of patients, the
      UCa:Cr increased and in 16% the increase indicated hypercalciuria (UCa:Cr > 0.2).
      CONCLUSIONS: Although the treatment of childhood asthma with budesonide 400
      micrograms/day via an aerochamber does not appear to be associated with
      hypercalciuria, the existence of a subgroup of patients in whom ICS may induce
      hypercalciuria is plausible. This needs to be further evaluated in a larger
      study.

PMID- 14679670
TI  - [Management of intractable migraine in adults].
AB  - The management of intractable migraine is not yet standardised. The first point
      in the emergency department is to eliminate severe cephalalgic non-migrainous
      disease, then to confirm the diagnosis of migraine. The second point is to
      determine trigger factors responsible for the refractory migraine--principally
      inadequate therapy, such as too low a dosage, inadequate treatment compared with
      intensity, and delayed treatment. Examples of inadequate classical treatments are
      presented for the following four main oral therapies: a nonsteroidal anti
      inflammatory drug (NSAID), analgesics, ergot derivatives, and triptans. When
      these drugs are ineffective, the following are used via injections: propacetamol,
      aspirin (lysine acetylsalicylate), injectable NSAIDs, and nefopam. These products
      differ from country-to-country. For example, morphinomimetics, phenothiazines and
      corticosteroids are widely prescribed in the US, while metamizole (dipyrone) is
      preferred in developing countries. The authors describe the different models of
      administration and the adverse effects of the substances. Finally, they describe
      the treatment of status migrainosus. Globally, triptans are underused in
      emergency departments. This review confirms the need for controlled trials of
      treatments for migraine in emergency departments in order to develop an
      international therapeutic consensus.

PMID- 14679671
TI  - [What are the criteria for evaluation and prevention of venous thromboembolism?].
AB  - Venous thromboembolism occurs frequently in both medical and surgical units.
      Although we possess the therapeutic means to prevent this condition, the question
      is how to assess the benefit induced by a treatment in relation to the
      haemorrhagic risk? The primary evaluation criteria and the evaluation method must
      be correctly chosen. While phlebography is the reference method for diagnosing
      deep venous thrombosis, the limitations associated with this method have led to
      the promotion of other diagnostic techniques, and clinical criteria or composite
      criteria are increasingly used. These different approaches--with their respective
      advantages and limitations--will be developed.

PMID- 14679672
TI  - [Dihydropyridines from the first to the fourth generation: better effects and
      safety].
AB  - Dihydropyridines are among the most widely used drugs for the management of
      cardiovascular disease. Introduced in the 1960s, dihydropyridines have undergone
      several changes to optimise their efficacy and safety. Four generations of
      dihydropyridines are now available. The first-generation (nicardipine) agents
      have proven efficacy against hypertension. However, because of their short
      duration and rapid onset of vasodilator action, these drugs were more likely to
      be associated with adverse effects. The pharmaceutical industry responded to this
      problem by designing slow-release preparations of the short-acting drugs. These
      new preparations (second generation) allowed better control of the therapeutic
      effect and a reduction in some adverse effects. Pharmacodynamic innovation with
      regard to the dihydropyridines began with the third-generation agents
      (amlodipine, nitrendipine). These drugs exhibit more stable pharmacokinetics, are
      less cardioselective and, consequently, well tolerated in patients with heart
      failure. Highly lipophilic dihydropyridines are now available (lercanidipine,
      lacidipine). These fourth-generation agents provide a real degree of therapeutic
      comfort in terms of stable activity, a reduction in adverse effects and a broad
      therapeutic spectrum, especially in myocardial ischaemia and potentially in
      congestive heart failure.

PMID- 14679673
TI  - [Angiotensin-converting enzyme inhibitors in congestive heart failure: clinical
      practice guidelines].
AB  - Angiotensin-converting enzyme (ACE) inhibitors are, at present, the cornerstone
      of therapy for congestive heart failure. Nevertheless, international literature
      and regional data have reported their underutilisation in the practice of
      cardiology. Despite the abundance of consensus conferences, none deal
      specifically with a therapeutic strategy using ACE inhibitors. In this context,
      clinical practice guidelines on the management of systolic heart failure with ACE
      inhibitors have been drafted in Lorraine by hospital cardiologists. The
      guidelines were formulated using a standardised procedure, combining a literature
      analysis and the opinions of experts. Seventeen guidelines were finally adopted,
      under four headings: indications and contraindications for ACE inhibitors;
      dosages and approaches to treatment monitoring; the management of adverse
      effects; and contraindications for concomitant therapy. The drafting of the
      clinical practice guidelines is the first step in a quality improvement
      programme, initiated in 1999 in the cardiology wards of the region.

PMID- 14679674
TI  - [Evaluation of different approaches to the treatment of arterial hypertension:
      combination treatment with low dose perindopril/indapamide versus sequential
      treatment of stepped-dose treatment].
AB  - A randomised double-blind comparison of three treatment strategies in 533
      patients with mild-to-moderate hypertension over 6-9 months. The low-dose
      perindopril/indapamide (PER/IND) combination (2 mg and 0.625 mg, respectively)
      daily resulted in a significantly better blood pressure control and systolic
      blood pressure decrease. In addition, the low-dose PER/IND combination showed
      superior efficacy/safety criteria than the sequential strategy of atenolol (50
      mg) then losartan (50 mg) then amlodipine (5 mg), and the step-by-step strategy
      of valsartan (40 mg then 80 mg then 80 mg plus hydrochlorothiazide 12.5 mg).

PMID- 14679675
TI  - [Evaluation of drug cost reduction resulting from the free supply of
      investigational drugs].
AB  - Excluding all other costs or benefits of participation in clinical trials, the
      objective of this study was to evaluate and analyse the cost avoidance
      represented by the free supply of the investigational drug in place of paying for
      a marketed drug. The cost avoided was defined as money that would most likely
      have been spent, but not because of inclusion of the patient in the clinical
      study. Only studies for which a marketed alternative drug was available with a
      standard dosage have been analysed. The numbers of delivered doses or the
      treatment durations were tabulated from pharmacy dispensing records for each
      study, and were used to calculate the medication cost avoided. No marketed
      alternative drug was available for 10 of 56 clinical studies. In total, in 2000,
      the cost avoidance was estimated between [symbol: see text] 585,492 and [symbol:
      see text] 603,674, with a wide variability between studies or between patients
      (CV: 120-520%). The two disease categories associated with the largest cost
      avoidance were multiple sclerosis and growth hormone deficiency. The cost
      avoidance was essentially of benefit to the medical insurance or the patient
      (98%) and was lower than [symbol: see text] 10,000 for the hospital, because 91%
      of patients are not hospitalised. So, why are clinical studies involving
      ambulatory patients performed in hospital? Of the 56 studies analysed, 46 could
      be shown to be non-innovative, because a marketed alternative drug was available.
      Few studies appeared to permit free access to treatment with non-reimbursable
      marketed drugs.

PMID- 14679676
TI  - [Adverse cardiovascular and central neurologic reactions to sympathomimetics used
      as nasal decongestants: results of the French National Pharmacovigilance Survey].
AB  - Remedies for coughs and colds often contain both an indirect sympathomimetic
      agent plus another drug (anti-inflammatory, analgesic or antibiotic, etc.). In
      France, oral sympathomimetics are available over the counter, and preparations
      for topical use (nasal sprays or drops) require a medical prescription. Using the
      French Pharmacovigilance database, we performed a retrospective study to identify
      cardiovascular and neurological adverse drug reactions (ADRs) associated with the
      use of nasal decongestants containing a sympathomimetic agent. Of a total of 165
      ADRs. 15 were strokes or cerebral haemorrhages. We also found the following: 67
      cases of arterial hypertension, 33 of convulsions, 28 of headaches and 24 of
      vasomotor symptoms involving the extremities. In most of these cases, misuse or a
      predisposing factor was found (such as a history of arterial hypertension or
      headache, the combination of two decongestants, long-term use, etc.). The
      incidence of cardiovascular or neurological ADRs with cold remedies seems 'very
      rare' but some of these reactions, mainly stroke, are 'serious'. However, there
      is no available clinical evidence showing the benefit of such agents after
      repeated use over several days. Since most of the nasal decongestants are freely
      available without prescription, drug information is needed to advise prescribers
      and also patients about risk of 'serious' ADRs with these drugs.

PMID- 14679677
TI  - [Acute dystonia from metoclopramide in children].
AB  - A retrospective study (1995-2000) of reports of cases of metoclopramide poisoning
      collected at the Lille poison control centre (184 phone calls) shows the frequent
      occurrence of acute dystonia in children (81 cases). These spectacular
      extrapyramidal symptoms consist of abnormal movements (31 cases), local
      hypertonia (30 cases), acute dyskinesia (17 cases), general hypertonia (16 cases)
      and oculogyric crisis (13 cases). There is no dose-effect correlation and sex has
      no influence on the occurrence of neurological symptoms. Medical management is
      simple surveillance or symptomatic therapy (a sedative drug and/or anti
      parkinsonian therapy and/or a gastrointestinal adsorbent). Hospitalisation was
      needed in only 9.1% of cases. Providing better information to physicians about
      metoclopramide adverse effects and their medical management should allow a
      reduction in the number of unnecessary hospitalizations.

PMID- 14679678
TI  - [Acamprosate (Aotal): could adverse effects upset the treatment of alcohol
      dependence?].
AB  - Acamprosate, a stimulant of central inhibitory GABA neurotransmision and an
      antagonist of excitatory amino acids, is used in alcohol withdrawal and for the
      maintenance of abstinence. After identification of several cases of treatment
      discontinuation during alcohol abstinence because of acamprosate-induced adverse
      drug reactions (ADRs), a retrospective study was conducted in order to
      investigate and quantify acamprosate-induced ADRs. Up to July 2002, 472 patients
      were included for treatment of alcohol withdrawal: of these, 68% (n = 322)
      received acamprosate. At least one ADR occurred in 98 patients (30%). The mean
      age of the patients was 41.5 +/- 8.8 years (range: 24-65) and 70% were male. All
      ADRs were classified as 'non serious'. However, ADRs required a dose decrease in
      61 cases or acamprosate discontinuation in 76 cases (62.2% and 77.5%,
      respectively, of patients with an ADR). We identified mainly gastrointestinal
      ADRs in 67 patients (mean delay before occurrence: 7.6 days), i.e. 20.8% of
      patients treated with acamprosate (corresponding to 68.3% of ADRs), with a
      positive rechallenge in five cases. Moreover, cutaneous ADRs (pruritus) occurred
      in 29 patients (mean delay before occurrence: 9.0 days), and required acamprosate
      withdrawal in 22 patients (75.9%) with a prior dose decrease in 18 of these
      patients (62.1%). Our results show that a dose decrease or withdrawal of
      acamprosate was necessary in 18.9% and 23.6%, respectively, of patients because
      of the occurrence of ADRs. The present study shows the important role of
      acamprosate-induced ADRs among the various causes for failure of alcohol
      abstinence.

PMID- 14679679
TI  - Acute pseudo-aldosteronism syndrome induced by liquorice.

PMID- 14679680
TI  - [Myasthenia after hepatitis B vaccination].

PMID- 14679681
TI  - Garlic interaction with fluindione: a case report.

PMID- 14679682
TI  - [Propafenone poisoning].

PMID- 14679683
TI  - [Fatal poisoning with propafenone: a case report documented with blood
      concentration levels].

PMID- 14679684
TI  - [The 110 th anniversary of the "Red Surgery"].
AB  - This october the 110th anniversary of the opening of the Krakow's "Red Surgery"
      will be celebrated. The Surgical Department of St. Lasarius Hospital and since
      1920, also the Second Department of Surgery of the Jagiellonian University were
      established in the building according to prof. Obalinski's concept. Among
      successors of prof. Obalinski there were many great surgeons like Rudolf
      Trzebicky, Maksymilian Rutkowski, Jan Glatzel, Kornel Michejda, Jan Oszacki and
      Otmar Gedliczka. The building of the "Red Surgery" now renovated and well
      equipped still hosts the Second Chair of Surgery of the Jagiellonian University
      containing the Departments of General Surgery, Endoscopic Surgery as well as the
      Department of Emergency Medicine and Multiorgan Injuries.

PMID- 14679685
TI  - [Incidence and risk factors of rebleeding from gastric and duodenal ulcers].
AB  - We present the analysis of risk factors of recurrence of bleeding in patients
      with gastric and duodenal ulcers. The group consisted of 178 patients
      hospitalized between 1998-2002. Among them there were 76 patients with gastric
      ulcers and 102 patients with duodenal ulcers. The recurrence of bleeding was
      observed in 24.3% patients with gastric ulcer and 21.8% of patients with duodenal
      ulcer. The most important risk factors were: localization of ulcers, intensity of
      bleeding according to Forrest scale, presence of concomitant diseases, shock on
      admission and H. pylori infection. 26.3% of patient with gastric ulcer and 36.4%
      with duodenal ulcer needed emergency operation. The mortality rate among patients
      with gastric ulcer was 15.6% and with duodenal ulcer 13.6%.

PMID- 14679686
TI  - [Minimally invasive techniques in the treatment of acute biliary pancreatitis].
AB  - 43 cases of consecutive bilary acute pancreatitis were treated by early
      endoscopic sphincterotomy and laparoscopic cholecystectomy within first 48 hours
      after admission. The basic cause of disturbance of bile outflow was
      microlithiasis. Course of the disease was monitored by level of proinflammatory
      interleukins in the blood serum of analysed patients. Marked decrease of their
      level after endoscopic sphincterotomy was observed. This decrease was progressed
      after laparoscopic cholecystectomy followed by continuos closed lavage of
      abdominal cavity. Our results indicated that minimally invasive techniques should
      be done in the early stage of mild and moderate cases of acute biliary
      pancreatitis.

PMID- 14679687
TI  - [Laparoscopic emergency surgery].
AB  - Up-to-dated concepts about the use of laparoscopy in the "acute abdomen" have
      been discussed. Most frequently performed procedures in abdominal emergency and
      trauma were presented. Indications, contra-indications, advantages and drawbacks
      with regard to own 10 years experience and literature were discussed.

PMID- 14679688
TI  - [Interventional ultrasonography of the abdomen].
AB  - Invasive ultrasound-guided procedures has recently become very popular. They
      proved to play important supplementary role in classic surgery, and now--in the
      era of "minimally invasive operative procedures"--became more frequently used. In
      178 patients treated from 1995 to June 2002 in 2nd Department of Surgery in
      Cracow, different "interventional sonography" procedures were performed. High
      efficacy and low morbidity related to the method confirm our statement that
      "interventional sonography" being less invasive than "classical surgery" should
      become the method of choice in the treatment of particular groups of patients.

PMID- 14679689
TI  - [Complications of left colonic diverticula].
AB  - Diverticula constitute the most common anatomical abnormality of the colon. They
      are usually located on the left side of the colon, especially within the sigmoid
      colon. Most of them remain asymptomatic and only 10-25% of the patients can
      develop complications--inflammatory ones or bleeding. Both types of complications
      have similar morbidity, but patients who suffer from bleeding are on the average
      10 years older as compared to group of patients who develop inflammatory
      complications. Vast majority of patients suffering from bleeding can be treated
      conservatively with overall mortality 2.8%. Mortality in the group of patients
      requiring an emergency/immediate operation for perforation of the diverticulum
      reached 18.2%. None of the patients suffering from diverticulitis without
      peritoneal signs on physical examination died--all of them were successfully
      treated conservatively. Therefore most of the complications of the colon can be
      treated conservatively, and surgical operation remains method of choice only in
      cases of massive bleeding or perforations.

PMID- 14679690
TI  - [Peritoneal adhesions as cause of small bowel obstruction].
AB  - Due to increasing number of people treated surgically there is a rising a problem
      of peritoneal adhesions. They can cause pain, infertility of young women,
      technical problems during successive operations and--last but not least-
      adhesional bowel obstructions. Patients operated on due to mechanical small bowel
      obstruction in the 2nd Department of Surgery from 1st January 1987 to 30th June
      2002 were included in the study. Diagnosis was set using clinical examination and
      imaging techniques such as X-ray and ultrasound and was confirmed during the
      operation. Strangulated hernia followed by peritoneal adhesions proved to be the
      most common causes of small bowel obstruction. Overall mortality rate in the
      group of adhesion-related obstructions reached 9.6%. In the group of 53 (39%)
      patients requiring small bowel resection mortality rate was 15.1%, and in the
      remaining patients, requiring only adhesiolysis--6.0%. There was markedly higher
      (18.4%) mortality rate noticed in the group of people older than 69 years as
      compared to younger patients (6.1%). More than twofold decrease in postoperative
      mortality rate observed throughout 15 years should be attributed to improvement
      of in-hospital care.

PMID- 14679691
TI  - [Treatment results in geriatric patients with acute abdomen in the intensive care
      unit].
AB  - Presented is material of 277 patients, who were treated due to acute abdomen
      illness in Intensive Therapy Unit at 2nd Department General Surgery Collegium
      Medicum Jagiellonian University during the time: from 01.07.1997 till 30.06.2002.
      This material regards only geriatric patients (patients > 65 years old). Patients
      analysis was divided into two main groups: patients with haemorrhagic shock
      caused by gastrointestinal bleeding (49 patients--group A) and by ruptured
      abdominal aneurysm (16 patients--group B), patients with hypovolemic and/or
      septic shock owing to diffuse peritonitis (150 patients--group C), and intestinal
      obstruction (62 patients--group D). The other principles of therapeutic
      procedures were described for every main group. In every illness group was
      showed: multiorgan dysfunction (acute myocardial ischemia with enzymatic and/or
      electrocardiographic changes, pulmonary oedema as acute left ventricular failure,
      respiratory and renal failure and metabolic dysfunction), actual punctuation into
      two scoring systems: APACHE II (28.8 points) and TISS-28 (44.5 points), time of
      hospitalization in the intensive therapy unit (mean 7.1 days), hospital's time of
      treatment (mean 17.5 days), mortality (for all patients 57.8%). These dates
      compared with dates from publications.

PMID- 14679692
TI  - [Insufficiency of arteriovenous fistulas in patients with end-stage renal failure
      -emergency surgical procedures].
AB  - From 1.07.1994 to 30.06.2001 in the 2-nd Department of Surgery and Department of
      Nephrology Collegium Medicum Jagiellonian University, in 274 patients with
      terminal renal failure 341 vascular access for hemo-dialysis have been performed.
      Acute insufficiency in functioning arteriovenous fistulas occurred in 93
      patients. In six of them, an attempt of thrombectomy was done. In 56 patients
      (group I) we carried out the new fistula on the same vascular level. In the
      remaining 31 cases (group II) we were forced to perform the procedure at a higher
      level. To compare late results in both groups of patients the method of Life
      Table Analysis was used. Cummulated index of patency (Pk) in the time interval 10
      12 months in two groups was 0.67. In the time interval 49-54 month in group I, Pk
      dropped to 0.38, in group II was 0.57. The study we carried out indicates that
      creation of vascular access on arterialized vessels, being profitable in many
      aspects, does not provide such long efficient functioning as those created on the
      new, higher level.

PMID- 14679693
TI  - [Surgical treatment of chronic venous insufficiency in own material].
AB  - Nowadays most issues regarding venous disorders are described as chronic venous
      insufficiency (CVI)-which is defined as all symptoms that manifestate as impaired
      blood outflow from the lower limbs or in general the result of blood stasis in
      the deep and superficial venous system. Due to the fact that the symptomatology
      of venous diseases is wide, the treatment should be multioriented and often as
      well multi-specialized. The treatment of CVI needs a good understanding of the
      etiology of the primary insufficiency of the superficial and the deep venous
      systems. The main purpose of the surgical therapy is to remove the reflux in the
      great saphenous vein and the perforating veins. Additionally, during the surgical
      treatment the various veins should be removed in a way that gives the best
      cosmetic effect. In this article we presented the analysis of different surgical
      treatments in patients diagnosed with CVI 2-4 grade according to CEAP scale. The
      patients were hospitalized in our Clinic between april 1998 and april 2003. This
      group consisted of 311 patients, among them were 257 patients with primary
      varices, 25 patients with recurrent varices and 29 with postthrombotic syndrome.
      The choice of surgery was based on clinical examination and the result of venous
      USG. The most frequent (62%) surgical therapy was removal of the great saphenous
      vein with miniphlebectomy. To make the treatment more efficient we used the
      endoscopic method of obliteration of the insufficient perforating veins in lower
      limbs, called subfascial endoscopic perforating surgery (SEPS).

PMID- 14679695
TI  - [Guidelines for severe multiple and multiorgan traumatic injuries].
AB  - Traumatic injuries have been described as the largest epidemic of the 20th
      century. In view of the number of victims and the associated costs, they have
      been also called the most severe and longest war of the contemporary world.
      According to Lipinski, every year every tenth Pole is involved in an accident and
      every one hundred-thirteenth Polish citizen requires specialist medical care.
      Thus, the general incidence is approximately 750 accidents per 100,000 Poles per
      year. 300,000 of them need hospital treatment, 30,000 die from accidents. Despite
      considerable progress in medical sciences and profound changes in the
      organization of emergency services within the past quarter of this century,
      multiple traumas continue to be a major problem in traumatology and the
      associated mortality rates in the best centers worldwide exceed 10%. Although,
      according to the recent reports, the most common cause of hospital deaths (30-50%
      or more of all fatal outcomes) is found in late complications of a severe trauma
      and posttraumatic shock, for example septic complications and multiorgan failure
      (MOF). Apart from severe primary injuries of the central nervous system,
      exsanguination continues to be the main cause of death (50-70%) immediately after
      the injury, at the site of the accident and in the ambulance (i.e. in the pre
      hospital period) and in the first hours of hospitalization. The third life
      threatening cause is acute respiratory insufficiency after thoracic trauma. The
      "golden hour" procedures are particularly described as a prehospital time period
      (ABC ... system), emergency room period (ATLS system), damage control period and
      other life saving operations period. The general conception of these standards is
      minimalization of the effects of shock, respiratory insufficiency and
      intracranial hypertension in multitrauma patients.

PMID- 14679694
TI  - [Chlamydia pneumoniae in patients with atherosclerotic ischemia of the lower
      limbs].
AB  - In the group of patients (n = 19), with advanced atheromatous ischemia of the
      legs the presence and titres of rum IgG, IgA, and IgM antibodies for Chlamydia
      pneumoniae (Cp) were measured. Those were compared with controls (n = 12).
      Additionally in the patients undergoing surgery (revascularisation or
      amputation), specimens of atheromatous arteries were examined for the presence of
      Cp. In the general population among the people at the age over 60 years the
      presence of antibodies was common (IgG 100%, IgA 92%). In the patients with the
      atheromatous ischemia of the legs the antibodies to Cp were found only in: IgG
      79%, IgA 79% of them. In 21% of patients (n = 4) we were able to confirm the
      presence of Cp in an artery wall. However we found that three of them had
      undetectable titres of serum IgG, IgA, IgM. In case of an individual patient
      seropositivity to Cp seems not to be a good marker of active chlamydial
      infection.

PMID- 14679696
TI  - [Evaluation of biological disability in patients after multiple injuries].
AB  - The aim of the study was the evaluation of biological disability of patients with
      multiple injuries in the aspect of the degree of disability. The study group
      comprised 521 patients treated effectively in the years 1994-1998 whose degree of
      injuries amounted to at least 18 scores in the Injury Severity Score (ISS). The
      prospective and partial retrospective study in the period of two to seven years
      included 367 (70.4%) patients. Their degree of biological disability was
      determined, also in the group below 30 ISS score and above 30 ISS score. In the 5
      year period 51.5% of patients were assessed as biological disable. Severe trauma
      patients obtained the greater percentage of disability. The highest amount of
      patients was observed with a mild degree of disability.

PMID- 14679697
TI  - [Own experience in arthroscopic surgery of knee injuries].
AB  - The aim of study was presentation of own experiences in arthroscopic surgery of
      knee joint injuries. The study group comprised 570 patients treated in the years
      1993-2002, in which the cause arthroscopy of the knee trauma was performed.
      Procedure of total or partial meniscectomy was the method of treatment in 270
      (47%) patients. Joint ligament reconstruction was made in 69 (12%) injured
      persons. The diagnostic arthroscopy was performed in 184 (32%) patients. As a
      small invasive method, it permits decrease costs of medical treatment, begins
      early rehabilitation and quickly vital reactivation.

PMID- 14679698
TI  - [Acute appendicitis--open or laparoscopic surgery?].
AB  - Laparoscopy is used more and more frequently in the treatment of abdominal
      emergencies including acute appendicitis. This technique has a lot of advantages
      especially in the group of the young female patients, where the differential
      diagnosis between gynecological diseases and appendicitis is difficult. AIM OF
      THE STUDY: The study is designed to compare the results of open and laparoscopic
      exploration in patients with suspected appendicitis. MATERIAL AND METHODS: From
      1998-2001 we performed 278 operations for suspicion of appendicitis in the 2nd
      Dept. of Surgery of the Jagiellonian University. There were 127 laparoscopic
      procedures performed in 46 men and 81 women (mean age 28.6 years) and 151
      classical exploration in 99 men and 52 women (mean age 37.9 years). We reviewed
      retrospectively the patients' data analysing age, sex, duration of the procedure,
      length of the hospital stay, intraoperative and postoperative complication rate.
      RESULTS: The patients operated classically were older than patients operated
      laparoscopically. The proportion of male and female patients was reversed in both
      types of exploration. The female patients composed a majority (2/3) in the case
      of laparoscopic procedures and minority (1/3) in the case of open operations. The
      average duration of open appendectomy was 43 min. as compared with 49 min. of
      laparoscopic procedure, which was however getting shorter in the analysed period.
      The mean length of the hospital stay was twice shorter after laparoscopic
      appendectomy (4.8 days vs 8.4 days). There were only 4 (3.15%) complications
      connected with laparoscopic technique and 34 (22.52%) complications after open
      appendectomy. There were 12 (9.45%) conversions, most of them in patients with
      the retrocoecal position of the appendix. The diagnosis of acute appendicitis was
      confirmed in similar percentage in both operation types (laparoscopy--78.74%,
      open technique--79.47%). There were also similar proportions of the patients with
      no macroscopical changes in the appendix and with other abdominal diseases.
      CONCLUSIONS: Laparoscopy allows for the precise diagnosis and final treatment in
      most patients with the suspected acute appendicitis. Some patients also avoid
      laparotomy. Hospital stay is significantly shorter and complication rate is
      markedly lower among patients operated laparoscopically.

PMID- 14679699
TI  - [Well-differentiated papillary mesothelioma--a rare neoplasm of the peritoneum].
AB  - Well differentiated papillary mesothelioma (WDPM) is a very uncommon neoplasm of
      peritoneum. Most frequently it appears like little numerous nodules on peritoneal
      surface, omentum or mesentery. WDPM is characterized by indolent course and is
      diagnosed in most cases incidentally during operations for other reasons.
      Sometimes differentiation between WDPM and other mesothelial lesions may be
      difficult. In the described case a 22 year old female, cystic peritoneal lesions
      were first recognized histological as WDPM. In verification after two months,
      they were proved to be cystic mesotheliosis. WDPM may cause adhesions followed by
      torsion or strangulation. In the second reported case a 24 year old male, WDPM
      provokes torsion of the omentum. Twelve months after operation and diagnosis this
      patient is symptom free.

PMID- 14679700
TI  - [Maffucci's syndrome with giant tumor of the thoracic wall].
AB  - Maffucci's syndrome is a rare nonhereditary malformation of mesodremal dysplasia
      origin which consists of multiple hemangiomas of the soft tissue and multiple
      enchondromas. Only approximately 170 cases of this disease have been reported in
      the literature. Maffucci's syndrome is known to be associated with tumors of
      mesodermal origin. Chondrosarcoma, osteosarcoma and angiosarcoma are the most
      common malignant neoplasms and the benign tumors consist of pituitary adenoma,
      adrenal cortical adenoma, parathyroid adenoma, thyroid adenoma and breast
      fibroadenoma. We present a case report of a 26-year old female patient with
      Maffucci's syndrome and a giant thorax tumor composed of fibroadenoma and
      canalicular adenoma.

PMID- 14679701
TI  - [Stromal tumor of the stomach in a 14 year old girl].
AB  - We present a case of a 14 year old girl with gastrointestinal stromal tumor
      (GIST) of the stomach. The patient discovered epigastric tumor on palpation. CT
      and ultrasound revealed tumor arising from the gastric wall, biopsy suggested
      GIST. Gastroscopically 6 cm policyclic lesion covered by unchanged mucosa has
      been visualized. Patient was submitted to operative management. There were no
      features of dissemination or invasion of surrounding structures. Stomach
      resection according to the Rydygier procedure has been performed. Histologically
      tumor arose from the muscularis propria. Mitotic activity was high 8/50.
      Immunohistochemical reaction against CD-117 was positive and in some parts
      against CD-34 which confirmed GIST. SMA and ALK were negative which excluded
      myogenic or inflammatory myofibroblastic tumor. Postoperative course was
      uneventful. There were no indications for adjuvant therapy. No recurrences were
      observed during follow-up.

PMID- 14679702
TI  - [Petit's triangle hernia clinically mimicking gluteal abscess].
AB  - Lumbar hernias are a very uncommon variety of abdominal wall defects. Diagnosis
      similar as obturatory hernia is often delayed until laparotomy. We describe a
      case of a 58 year old woman with parietal incarceration of the descending colon
      within a hernia in the inferior lumbar triangle (Petit's), under clinical form of
      a giant gluteal abscess.

PMID- 14679703
TI  - Balancing individual rights with the communal right to know: health care research
      and public policy.

PMID- 14679704
TI  - Patterns of change in marital relationships among parents of children with
      cancer.
AB  - This study examined changes in marital relationships among parents of children
      with cancer. Data for both parents of 35 children treated for cancer for less
      than a year to more than five years showed changes in marital relationships
      across 10 dimensions of the relationship. The findings showed that some aspects
      of the relationship (for example, communication and trust) tended to be
      strengthened, whereas others (especially sexuality) were prone to deterioration.
      Second, changes in the marital relationship were examined in relation to the
      duration of illness. The data showed a slight decrease in relationship
      satisfaction within one year of diagnosis, an increase in marital strength in
      cases of children who had been ill for two or three years, and a deterioration in
      the marital relationship after more than four years of children's illness.

PMID- 14679705
TI  - Sexual functioning following renal transplantation.
AB  - This study describes the prevalence of and investigates variables associated with
      problems in sexual functioning for a sample of 347 individuals following renal
      transplantation. Sexual problem was conceptualized through three continuous
      variables: lack of interest in sex; lack of enjoyment of sex; and difficulty
      becoming sexually aroused. Between 50 percent and 55 percent of respondents
      reported no sexual difficulties. The remaining respondents indicated from mild to
      severe problems. Multiple regression was used to examine predictors of problems
      with sexual functioning. Variables in the final model associated with sexual
      problems were older age and lower patient perceptions of physical and mental well
      being. Assessment of and education regarding sexual functioning must be a routine
      component of psychosocial intervention. Future research warrants investigation of
      the meaning of sexual function for this population.

PMID- 14679706
TI  - Alcohol use among pregnant African American women: ecological considerations.
AB  - Alcohol use across pregnancy causes growth and other abnormalities in the
      offspring. Confirmation of pregnancy leads some women to discontinue alcohol use
      and other women to continue use. The study discussed in this article assessed
      alcohol use at the first and third trimesters and at delivery for 393 pregnant
      African American women in an urban area. At the first trimester, 118 women were
      moderate to heavy drinkers (one or more drinks per day), compared with 38 women
      who were at delivery. Socioenvironmental and psychological differences were
      identified for both women who reduced consumption and women who continued. An
      understanding of continued drinkers' vulnerability to factors that influence
      their drinking behaviors demands the development of appropriate, early, and
      effective intervention strategies. Social welfare implications are discussed.

PMID- 14679707
TI  - Decision making by the child protection team of a medical center.
AB  - The study in this article examined the decision-making process of a child
      protection team (CPT) charged with reporting suspected child abuse in a medical
      center in Israel. The authors focused on the decision whether to conclude that a
      child was at imminent risk and whether to refer the case to a child protection
      officer. The authors analyzed the content of 139 case files of the children
      examined by the CPT in two consecutive years, recorded the case characteristics,
      and correlated them with the decision in a series of univariate and multivariate
      analyses. The findings indicate that the characteristics of the family were
      stronger predictors of the decision than the characteristics of the child and of
      the event that brought the child to the hospital. Implications of the findings
      and future research issues are discussed.

PMID- 14679708
TI  - Ethical decision making: pressure and uncertainty as complicating factors.
AB  - This qualitative study examines social workers' ethical tension as they evaluate
      decisional capacity of elderly individuals experiencing some degree of cognitive
      impairment. An interview guide of open-ended questions was used with a
      convenience sample of 17 home health care social workers. Constant comparative
      analysis was used to examine factors contributing to ethical tension. Three areas
      emerged as highly relevant to participants ethical decisions: (1) clinical
      uncertainty, (2) pressure from other professionals, and (3) a combination of
      pressure from other professionals and clinical uncertainty. Clinical uncertainty
      was influenced by partial cognitive impairment, mental health problems, the
      interplay of health and mental health, and unclear etiology of poor decisional
      capacity. Pressure from other professionals typically involved issues of
      compliance and medical safety. Ethical tension was particularly strong when
      participants experienced both pressure from other professionals and clinical
      uncertainty.

PMID- 14679709
TI  - Prostate cancer and psychosocial concerns in African American men: literature
      synthesis and recommendations.
AB  - African American men have the highest prostate cancer rates in the world, and
      more die from the disease than men from other racial or ethnic groups. Because
      the social work literature has little information on prostate cancer in African
      American men, the authors have synthesized the literature on prostate cancer and
      psychosocial concerns in African American men. They used the Health Belief Model
      as a framework to help explain, understand, and predict African American men's
      preventive health-related behaviors. The authors make recommendations for social
      work practice and research.

PMID- 14679710
TI  - Successful ways to increase retention in a longitudinal study of lead-exposed
      children.

PMID- 14679711
TI  - Medicare and premium support: a social work perspective.

PMID- 14679712
TI  - Decision making by the child protection team of a medical center.

PMID- 14679713
TI  - Editors' preface discursive bodies, embodied text.

PMID- 14679714
TI  - Metaphorical immunity: a case of biomedical fiction.

PMID- 14679715
TI  - Impacts of truth(s): the confessional mode in Harold Brodkey's illness
      autobiography.

PMID- 14679716
TI  - Sisyphus without knees: exploring self-other relationships through illness and
      disability.

PMID- 14679717
TI  - The doctor's role of witness and companion: medical and literary ethics of care
      in AIDS physicians' memoirs.

PMID- 14679718
TI  - Broken stories: patients, families, and clinicians after medical error.

PMID- 14679719
TI  - Reading bodies, writing bodies: self-reflection and cultural criticism in a
      narrative medicine curriculum.

PMID- 14679720
TI  - A gastroenteritis outbreak due to norovirus associated with a Colorado hotel.
AB  - Describing the system components of norovirus outbreaks is important in
      understanding how to prevent future outbreaks. Investigation of these components
      includes environmental, epidemiologic, and laboratory perspectives. This study
      describes how an investigation from these three perspectives was conducted and
      the significance of each component in understanding norovirus outbreaks. On May
      23, 2000, members of a professional group attending two meetings at a local hotel
      in Englewood, Colorado, began to complain of gastrointestinal illness. Sixty-nine
      illnesses were reported among 133 attendees. Eight hotel employees also
      complained of illness. Staff from the Tri-County Health Department and the
      Centers for Disease Control and Prevention investigated the outbreak. Three stool
      specimens collected from ill attendees contained norovirus. While the
      epidemiologic component did not identify a specific vehicle of transmission, the
      environmental investigation revealed food-handling practices, food handler
      perceptions, and hotel policies that may have contributed to disease
      transmission.

PMID- 14679721
TI  - Minimizing pathogenic bacteria, including spores, in indoor air.
AB  - Five experiments were conducted to assess whether aerosolized bacteria, including
      spores, respond like particulate contaminants to the primary (electrical) forces
      that control the distribution of small particulate contaminants in indoor air.
      Such response would suggest an approach to minimizing infection in offices,
      hospitals, nursing homes, and other facilities. It also would have implications
      for protection against intentionally introduced pathogenic bacteria, including
      spores. The experiments used two different genera and five different strains of
      bacteria, including spores. Micrococcus luteus was used as a surrogate for Gram
      positive cocci, because M. luteus is similar in size, shape, and cell wall
      composition to staphylococci, streptococci, and enterococci. Similarly, spore
      forming and vegetative Bacillus subtilis were used as surrogates for Gram
      positive bacilli such as Bacillus anthracis. The experiments were conducted in a
      dedicated aerosol physics test facility with culture-based measurements made at
      timed intervals. The results indicate that the organisms do respond like
      particulate contaminants to typical electrical forces in a room.

PMID- 14679722
TI  - Messages in the dust: lessons learned, post-9/11, for environmental health.

PMID- 14679723
TI  - Environmental-temperature injury in a Canadian metropolis.
AB  - This study performed a preliminary investigation of the incidence and
      determinants of environmental-temperature injury among residents of Montreal
      Island, Quebec, Canada. Incidence rates, mortality rates and determinants of
      environmental-temperature injury were estimated for Montreal Island's 1,802,309
      urban and suburban residents. Sources of information included coroner's reports,
      death certificates, hospital discharge summaries, and hospital chart reviews. The
      estimated incidence rate for environmental-temperature injury requiring
      hospitalization on Montreal Island was 3.1 per 100,000 person-years. The
      estimated mortality rate for all environmental-temperature injuries on Montreal
      Island was 0.3 per 100,000 person-years. The majority of hospitalizations and
      deaths were due to cold injury. Male gender, alcohol intoxication, psychiatric
      illness, older age, and homelessness were suggestive of important risk factors in
      cold injury. All deaths due to heat injury occurred in elderly females. Montreal
      Island's ambulance transport service, with its unique database, was identified as
      a novel surveillance design for environmental-temperature injury. Knowing more
      about the incidence and determinants of environmental-temperature injury may
      suggest priorities for interventions to decrease morbidity and mortality.

PMID- 14679724
TI  - Beyond general fund: environmental health revenues in a down economy.

PMID- 14679726
TI  - Smarter than you think. Although many European and Asian countries embrace smart
      cards with personal health information, U.S. healthcare organizations are slow to
      adopt them.

PMID- 14679725
TI  - The ADA and the Food Code: collision?

PMID- 14679727
TI  - The path to improved results. A Colorado hospital uses clinical decision support
      tools to lower LOS and its rate of unplanned readmissions and patient
      complications.

PMID- 14679728
TI  - At the crossroads of change and constancy. While technology advances and IT
      improvements directed at patient safety dot the landscape, healthcare CIOs remain
      focused on objectives to improve their organizations' performance-- and their own
      rewards, too.

PMID- 14679729
TI  - More of a good thing. Surgical information system upgrades help Pennsylvania
      hospital eliminate paper records and improve revenue management.

PMID- 14679730
TI  - Early experiences in e-prescribing. The state of Florida deploys handhelds and
      prescription management software to Medicaid physicians, to drive down the cost
      of medications and to provide point-of-care decision support for doctors.

PMID- 14679731
TI  - Transaction portal cuts costs. New York payers and providers discover that IT
      collaboration and the sharing of information affords savings that no organization
      could achieve on its own.

PMID- 14679732
TI  - Going with the flow. Tracking system helps midwest hospital streamline patient
      flow and lower emergency room divert rate.

PMID- 14679733
TI  - What works: remote intervention. South Dakota health ministry reviews records
      remotely to increase efficiency.

PMID- 14679734
TI  - Security hotlist.

PMID- 14679735
TI  - Incentives for healthy lifestyles.

PMID- 14679736
TI  - [Pathogenic bacteria in the respiratory tract of inpatient children with
      bronchial asthma].

PMID- 14679737
TI  - [Sino-bronchial syndrome progressed to respiratory failure despite minimal-dose
      macrolide therapy].

PMID- 14679738
TI  - [Azithromycin therapy for patients with intractable diffuse panbronchiolitis].

PMID- 14679739
TI  - [Therapeutic effect of macrolide antibiotics on surgical inflammatory stress
      following pulmonary surgical procedures].

PMID- 14679740
TI  - [Effects of azithromycin on pathogenic bacteria].

PMID- 14679741
TI  - [Effect of azithromycin on mucus secretion from nasal epithelium].

PMID- 14679742
TI  - [Effect of azithromycin on Cl ion transport in airway epithelial cells].

PMID- 14679743
TI  - [Influence of clarithromycin and azithromycin on cell cycle of neoplasms].

PMID- 14679744
TI  - Effect of long-term treatment with azithromycin on disease parameters in cystic
      fibrosis.

PMID- 14679745
TI  - [Elucidation of pharmacological mechanism of drugs by studying the receptors].

PMID- 14679746
TI  - [Influence of long-term macrolide therapy for chronic inflammation of respiratory
      tract on concurrent helicobacter pylori infection of stomach].

PMID- 14679747
TI  - [Effect of clarithromycin on pathogenic factors in Helicobacter pylori].

PMID- 14679748
TI  - [Therapeutic effect of macrolide antibiotics on murine model of hematogenous
      pulmonary MRSA infection].

PMID- 14679749
TI  - [Long-term effect of erythromycin therapy on Pseudomonas aeruginosa in chronic
      murine model of pseudomonas pulmonary infection].

PMID- 14679750
TI  - [Effect of macrolide antibiotics on secretion of MUC5AC in murine model of
      diffuse panbronchiolitis and related diseases].

PMID- 14679751
TI  - [Anti-influenza mechanism of macrolide antibiotics inducing airway IL-12
      production in murine influenza model ].

PMID- 14679753
TI  - [Prediction of influenza outbreaks and therapeutic efficacy of macrolide
      antibiotics].

PMID- 14679752
TI  - [Suppression of rhinovirus infections with macrolide antibiotics].

PMID- 14679754
TI  - [Beneficial effects of macrolide antibiotics on children with influenza].

PMID- 14679755
TI  - [Effect of macrolide antibiotics on VEGF production in nasal mucosa fibroblasts
      cultured under hypoxic conditions].

PMID- 14679756
TI  - [Effect of roxithromycin on inflammatory cytokine production in nasal polyp
      fibroblasts].

PMID- 14679757
TI  - [Suppressive effect of roxithromycin on NO production in fibroblasts of human
      nasal mucosa].

PMID- 14679758
TI  - [Effect of rapamycin on NF-kappaB induction].

PMID- 14679759
TI  - [Suppressive mechanism of clarithromycin on lipopolysaccharide-induced IL-8
      production in human monocytes by mediating AP-1 and NF-kappaB].

PMID- 14679760
TI  - [Suppressive effect of erythromycin on LPS-induced NF-kappa B activation in mouse
      lung].

PMID- 14679761
TI  - [Suppressive effect of roxithromycin on TARC production in epidermal cells].

PMID- 14679762
TI  - [Influence of erythromycin and the metabolite, EM201 on IL-2 receptor signaling].

PMID- 14679763
TI  - [Molecular biological study of action mechanism of macrolide antibiotics on
      CFTR].

PMID- 14679764
TI  - [Suppressive effect of spiramycin on cell division].

PMID- 14679765
TI  - [Long-term effect of roxithromycin on NO production].

PMID- 14679766
TI  - [Effect of erythromycin on peripheral neutrophil chemotaxis and experimental
      otitis media in rats].

PMID- 14679767
TI  - [Suppressive effect of roxithromycin on co-stimulatory molecule expression].

PMID- 14679768
TI  - [Effect of macrolide antibiotics on expression of transcription factors and
      surface markers in macrophages].

PMID- 14679769
TI  - [Effect of macrolide antibiotics on phagocytic clearance of apoptotic neutrophils
      by alveolar macrophages].

PMID- 14679770
TI  - [Effect of macrolide antibiotics on apoptosis of neutrophils--special reference
      to the suppressive effect on survival enhancing factor production in pulmonary
      epithelial cell].

PMID- 14679771
TI  - [Effect of macrolide antibiotics on induction of apoptosis in activated
      lymphocytes].

PMID- 14679772
TI  - [Macrolide therapy following endoscopic sinus surgery on patients with chronic
      paranasal sinusitis and sino-bronchial syndrome complicating bronchial asthma].

PMID- 14679773
TI  - [Combined therapy for patients with chronic paranasal sinusitis using a macrolide
      antibiotic and YAMIK catheter].

PMID- 14679774
TI  - [Combined drug therapy for patients with intractable paranasal sinusitis
      complicating allergic rhinitis].

PMID- 14679775
TI  - [Efficacy of combined drug therapy using a macrolide antibiotic and an
      antihistamine for adult patients with chronic paranasal sinusitis].

PMID- 14679776
TI  - [Guidelines in macrolide therapy for children with suppurative otitis media].

PMID- 14679778
TI  - [Evaluation of the concept of common mental disorders (CMD) and proposal of
      coninuum CMD (CCMD)].

PMID- 14679777
TI  - [Generalized anxiety disorder--on its disease concept].

PMID- 14679779
TI  - [Diagnosis and treatment of refractory cases of eating disorders].

PMID- 14679780
TI  - [An adult case suspected of recurrent measles encephalitis with psychiatric
      symptoms].
AB  - An adult case of suspected recurrent measles encephalitis with psychiatric
      symptoms is reported. A 46-year-old woman developed measles encephalitis
      presenting as schizophreniform disorder and recovered three months after onset.
      However, approximately two years later, she suffered a relapse of encephalitis
      presenting with psychiatric symptoms (auditory hallucination, cenesthopathy,
      insomnia, depressive mood) and became comatose. Following ten days of symptomatic
      treatment, her clinical symptoms gradually improved. Three months later, she made
      a remarkable recovery without neurological sequelae. Since then, she has
      maintained good condition for six years. The diagnosis of suspected recurrent
      measles encephalitis was made on the basis of the change of anti-measles IgM
      antibody titers. Acute relapse of disseminated encephalomyelitis (ARDEM) and
      multiple sclerosis (MS) were ruled out due to no abnormal finding of cerebral
      white matter on MRI. Six years after the recurrent episode, the titers of anti
      measles IgM antibodies (EIA) in the serum were still high, suggesting that she
      was suffering from a chronic measles virus infection. This patient should be
      followed up for a longer time because there is a possibility that she might be in
      the latent period of subacute sclerosing panencephalitis (SSPE).

PMID- 14679781
TI  - [Perospirone therapy in elderly patients with schizophrenia].
AB  - Perospirone is a novel serotonin-2 and dopamine-2 receptor antagonist (SDA)
      developed in Japan. Premarketing trials suggested that this agent was effective
      in reducing positive and negative symptoms of schizophrenia and had a favorable
      side-effect profile. However, these trials included only a few elderly patients,
      so the usefulness of perospirone in this population remains unknown. In this
      report we describe the treatment of 2 elderly patients with schizophrenia for
      whom perospirone therapy was efficacious. Case 1 was a patient with acute
      exacerbation of schizophrenic symptoms after discontinuance of medication. He was
      treated with 12 mg of perospirone daily and his symptoms reduced markedly from
      the 4th day of perospirone therapy. Efficacy was assessed by the positive and
      negative symptom scale (PANSS); all subscales of PANSS (positive symptom,
      negative symptom, and general psychopathology) reduced and the total score
      reduced from 78 to 38 by the end of the 6th week of treatment. No side effects
      such as extrapyramidal symptoms were noted. Thus, perospirone may be a useful
      antipsychotic for elderly patients with acute schizophrenia. Case 2 was a patient
      who had severe negative symptoms and extrapyramidal symptoms such as tardive
      dyskinesia, tardive dystonia, and sialorrhea. She had been hospitalized for more
      than 7 years. In this patient 12 mg of perospirone was administered daily after 3
      mg of risperidone had been tapered off. The negative symptom subscale and general
      psychopathology subscale in PANSS were gradually reduced after perospirone
      therapy was started. Extrapyramidal symptoms were assessed by the drug-induced
      extrapyramidal symptoms scale (DIEPSS), which consists of eight individual
      parameters and one global assessment, and each parameter is graded on a 5-point
      (0 = none to 4 = severe) scale. Sialorrhea, muscle rigidity, tremor, dystonia and
      overall sererity were improved more than 2 points by the end of the 6th week. The
      clinical course of this patient suggests that the clinical characteristics of
      perospirone and risperidone may be different, even though these agents are
      categorized into the same class of antipsychotics, SDA. Because this is a case
      report, evaluations are limited the clinical properties of perospirone. Further
      examination is necessary to evaluate the efficacy and safety of perospirone for
      elderly patients with schizophrenia, who are more vulnerable to the side effect
      of antipsychotics than the younger population.

PMID- 14679782
TI  - [Suicide among psychiatric patients in Fukuoka Prefecture].
AB  - To investigate suicide among psychiatric patients in Japan (mainly Fukuoka
      prefecture), a questionnaire survey was submitted to psychiatrists from
      departments of psychiatry of university hospitals in Japan, departments of
      psychiatry of Rosai Hospitals in Japan, psychiatric hospitals in Fukuoka
      prefecture, psychiatric clinics in Fukuoka prefecture, and departments of
      psychiatry of general hospitals in Fukuoka prefecture regarding their psychiatric
      patients who died from suicide (266 females and 267 males). A large proportion of
      the patients at completed suicide was aged within the thirties to fifties. The
      majority of patients suffered from either F3 (mood disorders) or F2
      (schizophrenia, schizotypal and delusional disorders) categories of the ICD-10
      classification. Approximately one-fifth of the patients in Fukuoka prefecture had
      jobs at the time of completed suicide. The main "occupational risk factors" that
      were found to be risks for suicide were "failure or overloaded responsibilities
      in their jobs" and "worsening business situation". The main "other risk factors",
      i.e., risk factors other than "occupational risk factors" were "worsening
      psychiatric conditions", "personal life events (e.g., somatic illness or marital
      discord)" and "life events in other family members (e.g., familial discord or
      familial problems)". Over 50% of all cases had both "occupational risk factors"
      and "other risk factors", suggestive of the necessity for multidimensional
      evaluation and care in the treatment of suicidal patients. Given that numerous
      males that suffer from psychiatric disorders commit suicide without seeing a
      psychiatrist, it is important to establish a system to treat them appropriately
      in order to prevent unnecessary deaths.

PMID- 14679783
TI  - [Evaluation of the simultaneous detection system for Chlamydia
      trachomatis/Neisseria gonorrhoeae DNA by the isothermal and chimeric primer
      initiated amplification of nucleic acids (ICAN)].
AB  - The isothermal and chimeric primer-initiated amplification of nucleic acids
      (ICAN) is a new isothermal DNA amplification method composed of exo Bca DNA
      polymerase, RNaseH and DNA-RNA chimeric primers. We developed the simultaneous
      detection system for Chlamydia trachomatis/Neisseria gonorrhoeae DNA, combined
      with luminescence detection by a probe hybridization. In the performance tests,
      this system was able to detect 10 to 100 copies of C. trachomatis/N. gonorrhoeae
      DNA for only 3.5 hours, and was highly specific to C. trachomatis/N. gonorrhoeae
      without any cross-reaction to C. pneumoniae, N. lactamica, N. sicca or N.
      meningitidis. When we tested 60 clinical samples of urine and cervical swabs, the
      interpretive results were completely consistent with those obtained by Roche PCR
      system. Of 13 positive samples by the ICAN and PCR systems for C. trachomatis,
      four were negative by EIA method(IDEIA Chlamydia). These results indicate that
      the ICAN system is an efficient and sensitive system to simultaneously detect C.
      trachomatis/N. gonorrhoeae DNA.

PMID- 14679784
TI  - [The present status of convergence in PSA reference values--from the surveillance
      in the Tokai-Hokuriku district].
AB  - The number of patients with prostatic cancer is recently increasing in Japan and
      it is well known that serum PSA determination is routinely used as a tumor marker
      of prostatic cancer. However, the reference values of PSA are widely varied,
      because the reactivities of the antibody to free PSA and ACT-PSA are different in
      each kit. Thus, there is no compatibility among values determined by available
      kits. In this study, we sent a questionnaire on PSA determination to 180
      hospitals with more than 200 beds. The recovery rate to the questionnaire was
      80.5% (145/180) and the determination was performed in house at 47 hospitals out
      of 145. Stamey in Stanford University recommended to set the ratio of complex PSA
      to free PSA 9:1 in the reference material. It is expected that PSA ad hoc
      committee in Japan reported that the inter-kit variability is becoming small. It
      can be said that the standardization for PSA determination is progressing. To
      discriminate prostatic cancer from benign prostatic hypertrophy, free PSA ratio
      or complex ACT-PSA is recommended. Further accumulation of data on PSA will be
      necessary to confirm this matter.

PMID- 14679785
TI  - [LDL-cholesterol-lowering effect of a mixed green vegetable and fruit beverage
      containing broccoli and cabbage in hypercholesterolemic subjects].
AB  - The serum LDL-cholesterol (LDL-C)-lowering effects of two types of canned
      beverage containing mixed green vegetables and fruits, with or without broccoli
      and cabbage (B&C), were examined in a randomized double-blind study design.
      Seventy-seven adults subjects with mild to moderate hypercholesterolemia
      participated in this study after giving their informed consent. The subjects were
      randomly divided into two groups. One group(test group) was allocated a test
      sample, containing B&C as the main materials. Another group(control group) was
      allocated a placebo sample made from the same materials but without B&C. The
      subjects were administered 2 cans of the assigned sample (160 g contents/can) per
      day for 12 weeks. Forty-nine out of 77 subjects, whose LDL-C levels were greater
      than or equal to 140 mg/dl and less than 180 mg/dl, were analyzed for the
      effectiveness. Serum LDL-C levels in the test group were significantly(p < 0.05)
      reduced at 3, 6 and 9 weeks after administration in comparison to the baseline
      levels (155.7 mg/dl in average). The average LDL-C value at 9 weeks was 142.5
      mg/dl and the reduction rate was 8.5%. But serum LDL-C levels in the control
      group were not significantly reduced. Significant differences(p < 0.05) between
      the groups were observed in the LDL-C levels at 6 and 9 weeks and also in the
      total cholesterol levels at 9 week. Thus daily intake of the beverage tested
      containing B&C are useful for lowering serum LDL-C levels in hypercholesterolemic
      subjects.

PMID- 14679786
TI  - [Study on the derivation of P300 with reference electrode in the oral cavity].
AB  - The event related potential P300 is useful as an index of the fall of the
      cognitive function attends by aging and the diagnosis of dementia. If the
      generator of P300 is assumed to be equivalent current dipole (ECD), the negative
      wave should be recorded at other sites which polarity differs from the positive
      wave on the scalp. This study is to determine the most suitable reference
      electrode site for P300 recording and to improve S/N of P300. In order to record
      the P300 or N300 potential which spread on the scalp, earlobe (A1), oral (X1) and
      under site of the nose(X2) was used as a reference electrode. Auditory oddball
      paradigm which consists of the acoustic sound of 2000 Hz (targets) and 1000 Hz
      (standards) was used for the measurement of P300. In this results, P300 or N300
      was measured by using earlobe(A1) site as a reference electrode. P300 wave was
      detected by Cz-A1 derivation and also the negative wave of N300 was detected by
      X1-A1 and X2-A1 derivation. These results demonstrate that there is an ECD which
      goes to the parietal region from internal focal area as a source of P300, and
      also suggest that P300 amplitude with Cz-X1 or Cz-X2 derivation is higher than
      that with Cz-A1 derivation. Therefore, it was speculated that the most suitable
      reference electrode sites for the improvement of the S/N in the P300 are oral
      (X1) or under the nose (X2) that show the negative potentials (N300).

PMID- 14679787
TI  - [Adipocytokines and life style-related disease].
AB  - The adipose tissue produces and secretes many bioactive substances, which we
      conceptualized as Adipocytokines (Nature Medicine 1996). Adiponectin is a novel
      adipocytokine, which we identified by screening the adipose-specific genes from
      human fat. Adiponectin is a secreted protein, the concentration of which reaches
      as high as 5-15 micrograms/ml in human plasma. Adiponectin mRNA is expressed
      exclusively in adipose tissues. The adiponectin mRNAs and its plasma levels are
      reduced in obesity, type 2 diabetes and atherosclerosis. Hyperinsulinemic
      euglycemic clamp studies in humans and monkeys, and several recent studies from
      others revealed that adiponectin is an insulin-sensitizing hormone. Furthermore,
      adiponectin exhibited anti-atherogenic moieties, decreasing the attachment of
      monocytes to endothelial cells through inhibiting the expression levels of
      adhesion molecules. It reduced the lipid accumulation in macrophages through
      reducing the expression of scavenger receptor, and inhibited the cytokine
      stimulated proliferation of smooth muscle cells. The genetic mutation of the
      adiponectin gene accompanying hypoadiponectinemia was strongly associated with
      the incidence of type 2 diabetes and atherosclerosis in Japanese subjects.
      Hypoadiponectinemia was the strongest predictor for the development of type 2
      diabetes in humans. Adiponectin knockout mice exhibited diet-induced diabetes and
      severer atherosclerotic response by vascular injury. Adiponectin supplement
      reversed the insulin resistance syndrome including diabetes and atherosclerotic
      change in the knockout mice. We conclude that "Hypoadiponectinemia" stands
      upstream of the pathophysiology of metabolic syndrome, hence, can be a direct
      target of drug intervention to tackle life style-related disease rampant in
      developed countries.

PMID- 14679788
TI  - [Platelet activation marker].
AB  - Atherosclerosis is the leading cause of death in patients with diabetes mellitus,
      increasing mortality in all forms of the disease. Classical risk factors,
      including hyperlipidemia, hypertension and obesity, do not completely account for
      the increased incidence of atherosclerosis in diabetes. Some platelet activation
      markers such as CD62P, CD63, PAC-1, Annexin V and platelet-derived microparticles
      (PDMP) are elevated in patients with diabetes, since diabetic platelets often
      have increased sensitivity to secondary aggregation in response to agonist. PDMPs
      are thought to play a role in clinical disease because they express phospholipids
      that function as procoagulants. High shear stress can initiate both platelet
      aggregation and shedding of procoagulant-containing PDMP, suggesting that PDMP
      generation by high shear stress occurs in small diseased arteries and arterioles
      under various clinical conditions. Platelet activation markers were significantly
      higher in the hypertensive or hyperlipidemic patients than in the controls.
      Selectins and cell adhesion molecules were also higher in the hypertensive or
      hyperlipidemic patients, and they were significantly higher in these patients
      with diabetes. Activated microparticles and PDMP may contribute to the
      development of atherosclerosis in diabetes, and platelet activation markers seem
      to be useful for the assessment of vascular damage in these patients.

PMID- 14679790
TI  - [Thioredoxin and atherosclerosis].
AB  - Increasing evidence has indicated that the modulation of intracellular redox
      states has marked influence on cellular events such as proliferation, activation,
      growth inhibition and death via the regulation of intracellular signal
      transduction and gene expression. Thioredoxin(TRX) is a multifunctional stress
      inducible protein which protects cells from various types of stresses. TRX shows
      not only scavenging activity for ROS, but also regulating activity for various
      intracellular molecules including transcription factors. Overexpression of TRX in
      transgenic mice attenuates adriamycin-induced cardiotoxicity by reducing
      oxidative stresses. We demonstrated that serum TRX levels are correlated with the
      severity of heart failure, and are negatively correlated with left ventricular
      ejection fractions in patients with heart failure. Moreover, we found that the
      serum TRX levels in patients with ACS were significantly higher than in SA,
      whereas no significant difference was found between patients with SA and control
      subjects. The expression of TRX is enhanced not only in endothelial cells and
      macrophages in the human atherosclerotic plaques, but also in balloon-injured rat
      arteries. These findings suggest that TRX and the redox system modulated by TRX
      play an important role in the cellular defense against oxidative stress in
      cardiovascular diseases including the progression of atherosclerosis.

PMID- 14679789
TI  - [Soluble Fc gamma RIIIa derived from macrophages].
AB  - Macrophages play a major role in the development of vascular lesions in
      atherogenesis. The cells express Fc gamma RIIIa (CD16) identical to that in NK
      cells, but with a cell type-specific glycosylation. The Fc gamma RIIIa molecules
      are released from the cell surface on activation, and these soluble forms (sFc
      gamma RIIIa) are present in plasma. We measured sFc gamma RIIIaM phi in plasma by
      Immuno-PCR with newly-developed anti-Fc gamma RIII mAb, MKGR14 (mIgM), which
      recognizes Fc gamma RIIIaM phi specifically. In healthy donors, the level of sFc
      gamma RIIIaM phi increased with age, and was positively correlated with LDL
      cholesterol to HDL-cholesterol ratios and LDL-cholesterol, but negatively with
      HDL-cholesterol. In addition, the sFc gamma RIIIaM phi level was related to the
      number of risk factors for atherosclerosis and correlated with carotid maximum
      intima-media thickness in subjects for annual medical checkup. The sFc gamma
      RIIIaM phi level was significantly increased in patients with coronary artery
      disease (CAD) with atherosclerosis, but not in patients with vasospastic angina
      (VSA) or intact coronary artery, compared with age-matched healthy donors. The
      sFc gamma RIIIaM phi level was related to the number of significant coronary
      artery stenoses, and positively correlated with LDL-cholesterol to HDL
      cholesterol ratios and lipoprotein (a), but negatively with HDL-cholesterol.
      These findings suggest that the macrophages are activated during the incipient
      stage of atherosclerosis, and that sFc gamma RIIIaM phi may serve as predictive
      marker for atherosclerosis.

PMID- 14679791
TI  - [Endothelium-dependent vasodilation in type II diabetes mellitus].
AB  - Endothelial dysfunction is a major feature of atherosclerosis and it can also
      serve as an early atherosclerotic marker. Evaluation and assessment of the
      endothelial function is important to prevent serious atherosclerotic disease
      especially myocardial infarction, cerebrovascular disease and renal failure. To
      evaluate endothelial function we measured endothelium-dependent vasodilation
      (flow-mediated dilatation: %FMD) of the brachial artery with ultrasound. This
      method is non-invasive and can be repeatable in order to follow patients
      individually. Progressive atherosclerosis is often observed in diabetic patients
      who are not hypertensive. To evaluate the impairment of the endothelial function
      in type 2 diabetic patients, we examined %FMD in them and compared with
      hypertensive patients without diabetes and control subjects. We found that type 2
      diabetic patients had the same endothelial dysfunction as hypertensive patients
      without diabetes. %FMD in both diabetic patients and hypertensive patients was
      lower than in control subjects. Moreover, %FMD of type 2 diabetic patients with
      hypertension was lower than %FMD of type 2 diabetic patients without
      hypertension. These finding suggests that endothelial dysfunction develops under
      the conditions of hypertension and hyperglycemia. Evaluating endothelial function
      with ultrasound is useful for assessment of atherosclerosis in diabetes.

PMID- 14679792
TI  - [Undergraduate education of laboratory medicine in Hirosaki University School of
      Medicine].
AB  - The Department of Laboratory Medicine is responsible for the several
      undergraduate educational programs in Hirosaki University School of Medicine. We
      describe here how these programs are taken place. The staffs of the department
      participate in premedical lectures for the first grade students under the name of
      "21st century education" to introduce the medical english, human science, health
      and disease. As an early clinical exposure, the first grade medical students
      spend half day to make rotational visit to major clinical departments in the
      University Hospital once a week. We show them how each section of the Department
      of Clinical Laboratory works. At Year 4 during preclinical courses, 15 credit
      lectures of laboratory medicine based on clinical core are provided by our staffs
      and invited lecturers. Year 4 students can also choose one of elective research
      courses. This year, 5 students studied three topics of diagnostic testing and
      derivative research in the setting of an academic clinical laboratory. The core
      clerkship in laboratory medicine includes the necessary skills for acquiring a
      blood sampling and performing core laboratory examination. Emphasis is placed on
      interpretation of the data as well as the sampling and examination. We have
      played some role in the introduction of tutorial learning methods into
      preclinical courses in the year of 2003. Although we need supply of directors
      manpower, we hope that all of the students can acquire quality of the generally
      permissive six year of medical school and prepare postgraduate educational
      programs through our education courses.

PMID- 14679793
TI  - [Undergraduate teaching project on clinical laboratory medicine].
AB  - Undergraduate teaching in clinical laboratory medicine is at the center of
      contemporary medical education. Students are expected to learn advanced
      laboratory medicine and basic diagnostic skills such as blood sampling,
      peripheral blood cell counting, blood typing, cross match test, urinalysis,
      electrocardiography, and bacteriological examinations through their training
      program. In our department, we have compulsory lectures, a basic practical
      training course and an advanced training course for the medical students. The
      compulsory lectures are programmed for the students in the fourth grade to obtain
      basic knowledge of clinical laboratory medicine and the patho-physiology of
      diseases. The teaching staff makes every effort to make their lectures exciting
      and interesting. As we experienced as medical students in the past, boring
      lectures give students nothing but a nap. For every senior teaching staff in our
      school, it is obligatory to be evaluated on their lectures by the students and
      other teaching staff every year to improve their teaching skills and materials.
      Teaching materials utilizing personal computers and the Internet are becoming
      more and more important. The basic practical training course is for the students
      in the fifth grade. The laboratory technicians help us teach students basic
      diagnostic skills in this program. The students in the advanced training course
      have to attend morning conferences in the department, including reverse clinico
      pathological conferences and laboratory investigations. The reversed clinico
      pathological conferences are popular among the students. Through our training
      programs, we hope that the students raise many questions that they solve
      themselves in the future, as well as learning established clinical laboratory
      medicine.

PMID- 14679794
TI  - [Educational program of clinical laboratory medicine to develop the ability to
      use proper laboratory examinations in medical practice].
AB  - A model core curriculum for medical education was proposed in 2001 as a guideline
      to standardize and improve the educational program in Japanese medical schools.
      Many subjects involved in clinical laboratory medicine were listed in this model
      core curriculum. Original and characteristic educational curricula in each
      medical school were also required in this guideline. In our university, we
      constructed the educational program of clinical laboratory medicine with
      lectures, clinical practice, and small group seminars including reversed CPC,
      according to the guideline. We need further trials to achieve the goal, i.e.
      education to develop the ability to use proper laboratory examinations in medical
      practice, as a good clinical doctor.

PMID- 14679795
TI  - [Our practical training program in laboratory medicine for medical students-
      Yamagata University].
AB  - At the Department of Laboratory Medicine at Yamagata University, our medical
      students are trained to have practical knowledge and the ability to plan
      laboratory examinations for the clinical diagnosis of patients. For 4th-year
      medical students, 31 clinical lectures are scheduled on a variety of subjects
      concerning laboratory findings. The 2-week practical training of 5th-year
      students includes an educational curriculum that allows them to master the
      various aspects of laboratory examinations, such as collecting blood samples,
      determining flow-volume curves, and conducting abdominal echograms. Finally, 6th
      year medical students undergo a 5-week training period during which they learn
      the essentials of laboratory examinations. We are proud of our present clinical
      curriculum for medical students. However, within a couple of years, the clinical
      educational program for medical students will be changed for the purpose of
      better preparing medical doctors in Japan. The advisory organ of the Japanese
      Ministry of Health, Labor, and Welfare has recommended the induction of a newly
      developed model core curriculum that will be nationally standardized and will
      focus on problem-based learning for medical students. Therefore, the present
      educational system, even in the field of laboratory medicine, will have to be
      changed.

PMID- 14679796
TI  - [New medical education of laboratory medicine at Tohoku University].
AB  - The purpose of this paper is to give an insight into the medical education
      program of our division at Tohoku University. Laboratory medicine in medical
      education is a field of learned basic clinical tests. Students have to learn the
      clinical laboratory through early clinical exposure in the first grade and try
      clinical technology through small-group learning in the fifth grade. Finally,
      they learn laboratory medicine such as infection control in our or another
      clinical hospital. The objects of our course are to encourage and promote the
      highest standards of training and post-graduate education of physicians and
      scientists at our university.

PMID- 14679797
TI  - [Education of clinical laboratory medicine in the premedical course of Fukushima
      Medical University].
AB  - Education of clinical laboratory medicine in the medical course of Fukushima
      Medical University School of Medicine is described. It include lectures (90 min,
      15 times) for the 4th grade students and practices for the 5th grade students
      (one week/2 w, 16 times) and for the 6th grade students (one week/2 w, 4-5
      times). In the practice course of 5th grade students, subjects concerning
      preanalytical issues have been employed to understand the importance. Specimens
      for practices are taken from every student, which include urines for urinalysis,
      feces for occult blood test, bloods for Wright-Giemsa staining and cell
      morphology and coagulation tests, and pharyngeal fluids for Gram staining. In the
      6th grade course, residual specimens from anonymous patients are used, and ECG
      examination is performed by the permission of patients. Through the experiences
      of sample collections and practices of elementary laboratory tests, students are
      expected to realize anxiety and pain of patients, to understand the importance of
      preanalytical variables and to master fundamental laboratory techniques as
      physicians.

PMID- 14679798
TI  - [Antibacterial chemotherapy in the era of multiple-drug-resistant bacteria--the
      current status and the prospect for the future].

PMID- 14679799
TI  - [Multiple-drug resistant bacteria: how do they come to exist, spread, and express
      their pathogenicity?].

PMID- 14679800
TI  - [Positioning of various anti-bacterial agents and their appropriate application
      in the era of multiple bacterial drug resistance. 1. Penicillins].

PMID- 14679801
TI  - [Positioning of various antibacterial agents and their appropriate use in the era
      of multiple bacterial drug resistance. 2. Cephem antibiotics].

PMID- 14679802
TI  - [Positioning of various antibacterial agents and their application in the era of
      multiple drug resistance. 3. Carbapenems].

PMID- 14679803
TI  - [Positioning of various antibacterial agents and their appropriate usage in the
      era of multiple drug-resistant bacteria. 4. Quinolones].

PMID- 14679804
TI  - [positioning of various antibacterial agents and their appropriate use in the era
      of multiple bacterial drug resistance. 5. Macrolides and ketolides].

PMID- 14679805
TI  - [Positioning of various anti-bacterial agents and their appropriate use in the
      era of multiple bacterial drug resistance. 6. Aminoglycosides].

PMID- 14679806
TI  - [Positioning of various anti-bacterial agents and their appropriate use in the
      era of multiple bacterial drug resistance. 7. Tetracyclines].

PMID- 14679807
TI  - [Positioning of various anti-bacterial agents and their appropriate use in the
      era of multiple bacterial drug resistance. 8. Glycopeptides].

PMID- 14679808
TI  - [Positioning of various antimicrobial agents and their appropriate use in the era
      of multiple drug resistance. 9. Anti-mycotic agents].

PMID- 14679809
TI  - [Positioning of various anti-bacterial agents and their appropriate use in the
      era of multiple drug resistance. 10. Anti-tubercular drugs].

PMID- 14679810
TI  - [Multi-drug resistant pathogens, positioning of various drugs, and their
      appropriate use: 1. Anti-HIV agents].

PMID- 14679811
TI  - [Innovation in antibacterial chemotherapy. 1. Significance and practice of
      combined use of anti-bacterial agents].

PMID- 14679812
TI  - [Innovation in anti-bacterial chemotherapy. 2. Introduction of the concept of
      PK/OD into anti-bacterial chemotherapy].

PMID- 14679813
TI  - [Innovation in anti-bacterial chemotherapy. 3. Allowable limit in the
      prophylactic use of anti-bacterial agents].

PMID- 14679814
TI  - [Innovation in anti-bacterial chemotherapy. 4. Safety evaluation of anti
      bacterial agents].

PMID- 14679815
TI  - [Anti-bacterial chemotherapy in the age of multiple bacterial drug resistance:
      Discussion].

PMID- 14679816
TI  - [Stiff-person syndrome benefited by high-dose intravenous immunogloblin].

PMID- 14679817
TI  - [Three cases of lung cancer with metastatic choroidal tumor].

PMID- 14679818
TI  - [Assessment of myocardial ischemia with nuclear cardiology in two patients with
      coronary ectasia].

PMID- 14679819
TI  - [Anemia and leukocytopenia associated with micrometal deficiency in long-term
      total parenteral nutrition].

PMID- 14679820
TI  - [Interstitial pneumonia associated with multiple myeloma].

PMID- 14679821
TI  - ["Beer potomania" in a Japanese rice wine drunkard].

PMID- 14679822
TI  - [Cytomegalovirus infection in a patient after splenectomy].

PMID- 14679823
TI  - [Infection-induced adrenal crisis in patients with postoperative hypopituitarism
      receiving corticosteroid replacement therapy].

PMID- 14679824
TI  - [Current status and future prospect of therapeutic agents for osteoporosis].

PMID- 14679825
TI  - [Current status and future prospect of virtual biopsy for the digestive tract].

PMID- 14679826
TI  - [Pleiotropic actions of angiotensin converting enzyme inhibitors].

PMID- 14679827
TI  - The burden of musculoskeletal conditions at the start of the new millennium.
AB  - Musculoskeletal conditions are extremely common and include more than 150
      different diseases and syndromes, which are usually associated with pain and loss
      of function. In the developed world, where these conditions are already the most
      frequent cause of physical disability, ageing of the most populous demographic
      groups will further increase the burden these conditions impose. In the
      developing world, successful care of childhood and communicable diseases and an
      increase in road traffic accidents is shifting the burden to musculoskeletal and
      other noncommunicable conditions. To help better prepare nations for the increase
      in disability brought about by musculoskeletal conditions, a Scientific Group
      meeting was held to map out the burden of the most prominent musculoskeletal
      conditions at the start of the Bone and Joint Decade. In particular, the Group
      gathered data on the incidence and prevalence of rheumatoid arthritis,
      osteoarthritis, osteoporosis, major limb trauma and spinal disorders. Data were
      collected and organized by world region, gender and age groups to assist with the
      ongoing WHO Global Burden of Disease 2000 study. The Group also considered what
      is known about the severity and course of these conditions, along with their
      economic impact. The most relevant domains to assess and monitor the consequences
      of these conditions were identified and used to describe health states for the
      different stages of the conditions. Instruments that measure these most important
      domains for the different conditions were recommended. It is clear from data
      collated that the impact from musculoskeletal conditions and trauma varies among
      different parts of the world and is influenced by social structure, expectation
      and economics, and that it is most difficult to measure impact in less developed
      nations, where the predicted increase is greatest.

PMID- 14679828
TI  - Industry, hospitals raise a toast to New Jersey nurses.

PMID- 14679829
TI  - Healing ... a time for reflection.

PMID- 14679830
TI  - We are putting our money where our mission is!

PMID- 14679831
TI  - Pesticides & health: 8 things holistic nurses can do.

PMID- 14679832
TI  - Updating our Florence Nightingale 2010 initiative.

PMID- 14679833
TI  - Fly fishing. A way of healing for breast cancer survivors.

PMID- 14679834
TI  - [Another indication for (erythro)keratodermia variabilis in livestock in the case
      of a neonatal lamb].
AB  - From skin biopsies of a neonatal lamb a congenital skin disease
      (erythro)keratodermia variabilis was diagnosed which especially showed besides an
      erythema formation a hyperkeratosis at some wound areas of the body. Despite of a
      sudden induced intensive therapy the lamb died. At the dissection of the carcass
      there were no further postmortem-findings which refer to another organic disease
      than the one of the skin. This case report is the second description of
      (erythro)keratodermia variabilis in domestic mammals, which is caused by an
      autosomal dominant inherited horning defect in humans.

PMID- 14679835
TI  - [Structure and clinical implications of the coronary horn stratification with
      special consideration of horn maturation, aging and decay processes in the equine
      hoof].
AB  - The three superimposing strata of the coronet and the ageing process and decay of
      the hoof horn were studied in 56 fore hooves of 28 domestic horses of different
      age and sex. Except for horn clefts at the weight bearing margin, their hooves
      did not show any signs of pathological changes. Their hooves did not show any
      signs of pathological changes. The investigation comprised the analysis of the
      structure and the mechanical-physical measurement of horn hardness. The own
      results showed that the functional and clinical importance of the three strata of
      the coronet concerns the absorption and distribution of the horizontal and
      vertical pressure and the resilient-elastical fixatia of the suspensory apparatus
      of the coffin bone to the inner spongiforme Stratum medium. Disruptive
      pathological changes may spread out between the different horn layers which
      sometimes leads to the phenomenon of the "Hollow Wall". The hard and stable
      coronet is composed of tubular and intertubular horn. Distal of the crest of the
      coffin bone the horn hardness decreases and clefts are visible which are
      interpreted as ageing processes. The medullar horn decays much faster in certain
      regions, thus enabling ascending infections especially in the white line area,
      causing "White Line Disease". Under consideration of the references the own
      results proved, that regular and professional trimming of the hoof can prevent
      these diseases and improves the pododermal blood circulation and the
      orthokeratotic cornification. By improving the stable hygiene and adequate
      nutritional supply with minerals and vitamins these measures can be supported.

PMID- 14679836
TI  - [Influencing factors on the level of the ovulation rate in sheep during the main
      breeding season--an ultrasonographic study].
AB  - The main breeding season for sheep in Germany is from the beginning of September
      until the end of November. The aim of this study was to determine the factors
      which influenced the level of the ovulation rate (o. r.) during this period. The
      examination was conducted over three years and included Booroola. Mutton Merino
      crosses [heterozygous- (F+) carriers and non-carriers of the Booroola- (FecB)
      fecundity gene], German Mutton Merino (GMM) and German Blackheaded (GB). In total
      1326 examinations were carried out. Between the 8th to 12th day after estrous
      detection an ovary diagnosis was performed by transrectal scanning with a 7.5 MHz
      linear probe. The number of the corpora lutea per ewe (o. r.) was documented. The
      weight and the body condition of the ewes was also determined. During the
      breeding season the breed of the ewe had the main effect on the level of the o.
      r. (p < 0.05). This is the reason that the statistical model can only be applied
      for each breed. The effects of age, year of examination and day of the main
      breeding season were tested. The age of the ewes and the date of the examination
      during the breeding season had the main effect on the o. r. In GMM and GB the age
      influenced the o.r. with an effect of 8.3% and 4.2%. The effect of the season was
      vice versa (Gmm 3.2%; GB 8.2%). Non-carriers of the Booroola- (FecB) fecundity
      gene behaved similar like the GMM. However, only the high fecundity carriers of
      the FecB-gene were strongly influenced by the season. For each breed there exists
      a typical threshold value for the body weight above which further weight has no
      effect on the o. r. (GMM 65-70 kg, GB 75-80 kg, non-carriers of the Booroola-FecB
      gene 55-60 kg and carriers of the FecB-gene 60-65 kg). This value lies at about
      80% of the highest measured weight of each breed. The results demonstrated that a
      balanced age structure in combination with a optimum weight influenced the level
      of o. r. In addition the date of the season is especially important.

PMID- 14679837
TI  - Monthly changes in some reproductive parameters and in testosterone and thyroxine
      values of rams throughout one year under continental climate conditions.
AB  - Ten sexually mature rams were used in this study. Blood and semen was collected
      monthly from rams for one period of 12 months to study semen characteristics and
      to determine serum testosterone and thyroxine (T4) hormones. Results showed that
      all of the rams are continuous breeders as they show sexual desire and produce
      semen throughout the whole year. However, monthly variations in reproductive and
      semen characteristics were detected. Relative testes volume, ejaculate volume,
      sperm motility, sperm concentration and serum testosterone levels were higher
      during autumn months than at other months of the year. In addition, autumn months
      showed moderate percentage of abnormal spermatozoa. Furthermore, serum T4 was
      significantly higher in summer and autumn months than that observed in winter and
      spring. These results indicate that ram semen quality in Afyon continental
      climate conditions may be better during late summer and early autumn months than
      during other months of the year.

PMID- 14679838
TI  - [Bilateral anophthalmia associated with further anomalies of the head in German
      Holstein calves].
AB  - Two female calves of the breed German Holsteins showing bilateral anophthalmia
      and deformations of the jaws such as brachygnathia superior and bilateral cleft
      of lips and noses, respectively, were born on two different farms. Similar
      congenital defects could be found neither in the relatives of the affected calves
      nor in other animals of the same herds. A monogenic autosomal recessive
      inheritance may have caused bilateral anophthalmia. Chromosomal aberrations could
      not be detected in the affected calves. The possible environmental causes such as
      infection by the BVD-virus or oversupply or deficiency of vitamin A are very
      unlikely.

PMID- 14679839
TI  - [Cytogenetic and histologic examination of four tortoiseshell cats].
AB  - Tortoiseshell colored tomcats are very uncommon. In most cases their phenotype is
      caused by an aberration of sex chromosomes. In this study, we carried out
      cytogenetic investigations in four tortoiseshell tomacats. In two cases, an XXY
      syndrome could be proven. Another tortoiseshell tomcat had an XX/XY chromosomal
      constitution. One tomcat showed an exclusively male XY karyotype. In two cases
      the testes were histologically examined. In one XXY phenotypically male cat there
      was no spermatogenesis present. In the tomcat with XX/XY-chimerism
      spermatogenesis was seen in some testicular tubules.

PMID- 14679840
TI  - [Importance of estrogens and estrogen-active compounds for udder health in
      cattle. A review].
AB  - High oestrogen concentrations in blood or high intake of oestrogen-active
      compounds with forage can be associated with an enhanced occurrence of udder
      diseases. Mean somatic cell count (MSCC) can increase and milk yield can
      decrease. Subclinically infected udder quarters can develop clinical mastitis and
      the rate of new infections can be high. This review describes concentrations of
      oestrogens in peripheral blood plasma in cattle and occurrence of oestrogen
      active compounds in forage. Relationships between oestrogens or oestrogen-active
      compounds and udder health are presented. The possible mechanisms of enhanced
      susceptibility of the udder to infection under the influence of oestrogens are
      discussed.

PMID- 14679841
TI  - Vaccination of weaned pigs against oedema disease.
AB  - The trial was performed in a pig-production unit with high prevalence of
      postweaning oedema disease (ED). An experimental inactivated VT2e-toxoid vaccine
      was produced. Two randomised treatment groups of piglets were formed. The animals
      in one group (n = 351) were vaccinated intramuscularly at 1 week of age with 12.5
      micrograms and at 3 weeks of age with 25 micrograms of inactivated VT2e toxin.
      The other group (n = 350) was placebo treated. We evaluated: average daily
      nursery weight gain, nursery mortality due to ED, fattening average daily weight
      gain until slaughter and VT2e-specific antibody titres. Serological tests were
      performed four times: before first vaccination, at weaning, at the end of nursery
      period and at an age of 4 month. Vaccination improved nursery average weight
      gains (301 +/- 31 g/day vs. 278 +/- 41 g/day). Mortality due to edema disease
      decreased in vaccinates: 0.9% vs. 6.9%. Fattening average daily weight gain until
      slaughter did not differ between the groups (711 +/- 41 g vs. 708 +/- 46 g).

PMID- 14679842
TI  - [Heat-shock proteins in myocardial ischemia].
AB  - Heat-shock proteins (HSP) are a group of highly conserved proteins, which
      production is induced as a intracellular response to different kinds of stresses.
      They are also included in the group of chaperones, which are involved in protein
      folding and refolding in the cells, stabilising of macromolecular structure and
      repairing of denatured proteins or promoting their degradation when damages are
      too advanced. Because of protective role of HSP on the cellular level, a lot of
      studies is focused on the place of HSP in cardioprotection. The exact mechanism
      of this activity is still unknown. The experiments provided convincing proofs
      that cardiomyocytes which were subjected to hyperthermia or many other stress
      factors were reacting increased synthesis of HSP what guaranteed protection
      against further, stronger episodes of different stresses. The problem, which is
      still actual, is finding the possibility of taking advantage of cardioprotective
      properties of HSP in the treatment. Such a situation is due to lack of
      noninvasive methods of inducing HSP expression. The present study is a kind of
      review of literature taking up this problem, starting with protocols using
      hyperthermia, through the pharmacological therapy and ending with molecular
      techniques and genetic engineering.

PMID- 14679843
TI  - [Subjective perception of hypersensitivity to selected additives-containing foods
      in children and adolescents from schools in Bialystok].
AB  - The incidence of adverse reactions to food additives is difficult to establish
      and therefore not completely known. The aim of the present study is an attempt to
      determine the actual incidence of this problem in the population of school-age
      children and adolescents. The current work is the preliminary stage of this study
      and contains recapitulation of information obtained from parents and foster
      parents of 5044 children aged 6-16 years from Bialystok. Analysis of data has
      revealed that 9.8% of children complain of undesired symptoms after consumption
      of additive-containing foods. The problem referred to younger children
      statistically significantly more frequently (p < 0.05), while no correlation was
      found with sex (47.9% boys, 52.1% girls). The foods most frequently associated
      with adverse symptoms appeared to be: sparkling drinks e.g. Coca-Cola, orangeade-
      9% and sweets products (e.g. chewing-gums, crisps, sweets, cakes)--6.4%. The most
      common symptoms related to the consumption of additive-rich foods were: abdominal
      pain--9.9%, cutaneous rash--8.8%, cough and rhinitis--5.5% and 5.6%, headache-
      4.9%. The preliminary findings should be verified using double-blind placebo
      controlled food challenge tests in order to establish the actual incidence of
      food additive intolerance.

PMID- 14679844
TI  - [Comparison of subjectively perceived hypersensitivity to selected additives
      containing foods among children with and without food allergy/intolerance].
AB  - The incidence of adverse reactions to food additives is difficult to establish
      and therefore not completely known. The equally important problem is to what
      extent food additives induce ailments and to what degree they exacerbate symptoms
      of the already existing disease, e.g. urticaria, atopic dermatitis, asthma or
      rhinitis. The aim of the present study is to establish the actual incidence of
      this problem in the population of school-age children and adolescents. This work
      presents the preliminary evaluation. Analysis of the questionnaire data obtained
      from parents or foster-parents of 5044 children aged 6-16 years from Bialystok
      has revealed that 9.8% of children complain of subjective adverse symptoms after
      consumption of particular foods containing additives. The aim of this stage of
      the study is to determine and compare the incidence of adverse symptoms ascribed
      to food additives in the group of children with food allergy and/or intolerance
      and in unburdened children. The incidence of each of the evaluated features (i.e.
      type of food, clinical symptoms) was statistically significantly higher in
      children with symptoms of allergy or intolerance (p < 0.001).

PMID- 14679845
TI  - [The assessment of the influence of IgE-mediated food allergy on colonic transit
      time in children with chronic constipation].
AB  - The aim of the study was a comparative analysis of patients with chronic
      constipation and coexisting food allergy in relation to patients with functional
      chronic constipation without food allergy. 325 children with chronic constipation
      aged 0.6-17.1 years (mean 8.0 +/- 4.3) were included into the study. The IgE
      mediated food allergy was diagnosed in 179 children. Results of anthropometric
      measurements, rectoscopies, abdominal ultrasonographies, evaluations of colonic
      transit time and anorectal manometric examinations, together with clinical
      symptoms, were analysed and compared. The results were subjected to statistical
      analysis. There were no significant differences in clinical presentation,
      anthropometric measurements, rectoscopic, ultrasonographic, manometric and
      histopathological findings between both groups. In the food allergy group the
      total and segmental colonic transit time more frequently was prolonged,
      manifested usually as colonic inertia (p < 0.001). Food allergy can be clinically
      manifested as a chronic constipation. IgE-mediated food allergy may significantly
      prolong colonic transit in affected patients.

PMID- 14679846
TI  - [Alteration of serum interleukin-1 receptor antagonist and interleukin-6 levels
      after surgical injury].
AB  - The aim of the study was to investigate alterations in systemic production of
      interleukin 1 receptor antagonist (IL-1Ra) and interleukin 6 (IL-6) following
      major abdominal surgery in oncologic patients and in patients after minor
      surgical trauma who had undergone open cholecystectomy (OC). Studies were carried
      out in 30 patients. The concentrations of IL-1Ra in oncologic patients (865 +/-
      1021 pg/ml) before operation were significantly higher (p = 0.042) in comparison
      with OC group (466.16 +/- 389 pg/ml). There was a significant (p = 0.017)
      increase in the IL-1Ra level to 2735 +/- 1943 pg/ml on day 1 after major surgery
      and the IL-1Ra level remained significantly elevated until the day 10. The IL-1Ra
      values were significantly increased on day 1 after OC (843.93 +/- 627 pg/ml, p =
      0.001) and remained significantly (p = 0.02) elevated until the 10 postoperative
      day. The IL-1Ra serum concentrations were significantly higher on day 1 to 10
      after major surgery with complications compared with patients after OC and
      uneventful postoperative course. The preoperative concentrations of IL-6 in
      oncologic patients was 24.9 +/- 64 pg/ml and in OC patients 8.35 +/- 14 pg/ml.
      The level of IL-6 on the day 1 after the major operations was ten times higher
      (268.38 +/- 330 pg/ml, p = 0.002) and remained significantly elevated over the
      ten days period. The highest concentration of IL-6 was observed in oncologic
      patients with severe complications (384.7 +/- 484 pg/ml). The significantly lower
      level of IL-6 (p = 0.009) was seen after OC in patients with uneventful
      postoperative course (50.6 +/- 53 pg/ml on the 1st postoperative day) as compared
      to major surgery. We conclude that elevated serum concentrations of IL-1Ra and IL
      6 on the day 1 following surgery represent early sensitive markers of the extent
      of surgical trauma. The monitoring of changes in IL-1Ra and IL-6 blood levels may
      be useful in early recognising of pathological response to surgical trauma in
      oncologic patients after major surgery with increased risk of the development
      severe complications.

PMID- 14679847
TI  - [Cerebral strokes in patients with systemic lupus erythematosus].
AB  - We examined a group of 83 patients (81 females and two males) diagnosed as
      systemic lupus erythenatosus (SLE) aged 19-77, with the mean duration of the
      disease of seven years. All patients had neurological examination and
      electroencephalography (EEG) complemented with magnetic resonance image (MRI) and
      single photon emission computed tomography (SPECT) in same cases. Among 83
      patients we found the group of five (females) showing acute, stroke-like
      symptoms. Subarachnoid haemorrhage from a vascular malformation was diagnosed in
      one case. In four cases ischemical syndromes were observed mainly without strong
      clinical expression, with tendency to recede. In one patient the stroke was the
      first symptom of SLE. All these patients revealed abnormalities both in
      neurological examination and in neuroimaging techniques--as small, hyperintensive
      foci in MRI and multiple, diffused areas of decreased cerebral blood flow found
      in all but one cases in SPECT which seems to be the most sensitive method. In
      conclusions we want to stress that observed ischemic syndromes in patients with
      SLE were acute but of moderate intensity, with tendency to recede swiftly;
      transient ischemic attacks (TIA) were comparatively frequent. Acute stroke-like
      episodes might be the first symptom of SLE.

PMID- 14679848
TI  - [Analysis of labor methods after cesarean sections in the last 50 years].
AB  - The aim of the work was to analyze the incidence and changes in the labors after
      previous cesarean section in the last 50 years. The study was conducted on the
      basis of the labors documented in our Clinic between 1946 and 1996 year. Cesarean
      sections are more and more frequent in these years and the amount of the patients
      with previous cesarian section elevates. We observed the increase rate of repeat
      cesarean delivery in comparison to vaginal birth after cesarean section. The
      trial of vaginal labor after cesarean section is usually successful in young
      patients (under 25 years old), repeat cesareans is mainly observed in patients
      older than 35. The permanent decrease in the incidence of instrumental deliveries
      in comparison with cesarean section was observed. The trial of vaginal labor
      after cesarean section, after exclusion of contraindicatins, should be routine
      procedure decreasing the amount of cesarean sections.

PMID- 14679849
TI  - [Influence of exercise on plasma concentration of neuropeptide Y in patients with
      essential hypertension].
AB  - Overactivity of sympathetic nervous system may lead to hypertension. The aim of
      this study was to assess changes of plasma concentration of neuropeptide Y in
      patients with hypertension after exercise. MATERIAL AND METHODS: The study group
      consisted of 46 patients with hypertension; the control group consisted of 29
      healthy individuals. Plasma concentrations of neuropeptide Y, aldosterone,
      catecholamines and plasma renin activity were assessed before and after exercise
      performed on the treadmill. RESULTS: Plasma concentrations of aldosterone,
      catecholamines and plasma renin activity increased in both groups but plasma
      concentration of neuropeptide Y increased only in the hypertensive group (52.4 +/
      100.2 pg/ml vs 103.4 +/- 206.7 pg/ml, p < 0.05) but not in controls (51 +/- 36.3
      pg/ml vs 70.8 +/- 134.9 pg/ml, p = NS). CONCLUSION: The increase of plasma
      concentration of neuropeptide Y after exercise in hypertensive group, but not in
      controls, indicates sympathetic nervous system overactivity in the study group.

PMID- 14679850
TI  - [Effect of interleukin 15 on the PMN activity in Lyme borreliosis].
AB  - In the present study, the effect was examined of rhIL-15 on neutrophil (PMN)
      activity (locomotion, phagocytosis and NBT reduction) in patients with Lyme
      disease. We found an increase of all parameters after IL-15 stimulation. The sera
      from the patients contained increased level of IL-15 in relation to controls. The
      results obtained indicate the modulatory effect of IL-15 on the PMN activity
      during Lyme disease.

PMID- 14679851
TI  - [Asthma-induced myocardial infarction in a 39-year-old woman].
AB  - A 39-year-old woman, without any previous cardiac history, is reported who
      developed a myocardial infarction during an attack of allergic asthma. Since
      childhood she has been treated with short acting beta 2-adrenoceptor agonists
      because of mild atopic asthma. After exposure to cat's allergen she suddenly
      developed a severe attack of dyspnea and cyanosis. She improved rapidly after
      administration of oxygen, glucocorticosteroids, aminophilline and beta 2
      adrenoceptor agonist. Laboratory examinations of serum revealed elevation in
      enzymes activities of aminotransferases, creatinine phosphokinase and troponin I.
      In spite of absence of typical electrocardiographic changes we suspected
      myocardial infarction. The diagnosis was confirmed by echocardiography, which
      showed akinesis of anterior wall of the heart. On the base of relevant literature
      we discuss the hypothesis of cardiac necrosis in severe attack of asthma and the
      role of cardiac enzymes, especially troponin, in the process of diagnosis.

PMID- 14679852
TI  - [Iatrogenic hyperlipidemia after l-asparaginase and glucocorticoid treatment in
      two children with acute lymphoblastic leukemia].
AB  - L-asparaginase and glucocorticosteroides are the main drugs used in the first
      line treatment in children with acute lymphoblastic leukaemia. One of the
      observed side effects in the increase of serum level of triglycerides is
      synergistic manner. The paper describes two children with acute lymphoblastic
      leukaemia. In these patients we could observe remarkable hypertriglyceridemia,
      and hypercholesterolaemia with the increase of LDL-cholesterol after applying
      high doses of L-asparaginase and glucocorticosteroids simultaneously. The above
      mentioned disorders were transient. In the analysis of the possible reasons of
      this pathology we took into consideration family predispositions, the transient
      deficit of lipoprotein lipase induced by L-asparaginase, improper diet and
      hyperthyroidismus.

PMID- 14679853
TI  - [Systemic sclerosis: symptomatic treatment].
AB  - Systemic sclerosis is an autoimmune connective tissue disease resulting in a
      fibrosis of skin and internal organs. The pathogenesis is unclear and includes
      genetic and environmental factors leading to an immune activation, vascular
      abnormalities, fibroblast proliferation and collagen deposition. The treatment of
      systemic sclerosis can be based on a model of its pathogenesis. Therapy includes
      vasoactive drugs, prevention of fibrosis or immunosuppression and symptomatic
      treatment. In our paper we present the proven remedies and novel therapies of
      systemic sclerosis--disease extremely difficult to treat because of changes in
      digestive, pulmonary, cardiovascular, neuromuscular and locomotor's systems.

PMID- 14679854
TI  - [Systemic sclerosis: drugs and new therapeutic methods].
AB  - The purpose of our review is to present conventional drugs as well as innovative
      treatment concepts for systemic sclerosis, particularly with their effects on the
      most important pathogenetic mechanisms of this disease. Date from literature
      indicates that all therapeutic methods are connected with occurrence of side
      effects, therefore in our paper we focused on benefits and disadvantages of
      therapeutic options for systemic sclerosis.

PMID- 14679855
TI  - [Protein composition and structure of the myelin sheath. Part I].
AB  - During the past few years, significant advances have been made in meeting
      structure of myelin sheaths and the mechanisms participating in myelination and
      demyelination. Myelin is formed by Schwann cells in the peripheral nervous system
      (PNS) and oligodendrocytes in the central nervous system (CNS). Myelin is
      composed of several layers of membranes wrapped around axons. In contrast
      majority of biological membranes both CNS and PNS myelin is characterized by a
      high ratio between lipids and proteins. Myelin in CNS and PNS don't differ in
      respect to lipids, but their protein components are different. Better
      understanding of myelin structure and function and as well as processes of
      myelination and demyelination will help to clarify some aspects of demyelinating
      diseases and injures in the nervous system.

PMID- 14679856
TI  - [A dilemma of using psychotropic drugs in pregnancy and breast feeding].
AB  - The treatment of psychiatric disturbance during pregnancy and breast feeding
      presents for psychiatrics a big challenge and very difficult dilemma. The
      psychopharmacotherapy during these periods should always involve a careful
      analysis of the risks and benefits of treatment which needs co-operation between
      obstetricians and psychiatrists. The purpose of this article is to review present
      scientific reports on the use of psychotropic drugs in pregnancy, puerperium and
      during breast feeding. The article brings forward psychopharmacotherapy in aspect
      of eventual risks for occurrence of teratogenecity, perinatal and postnatal
      toxicity in the neonate and in the breast feeding. The guidelines described
      concern the treatment of the psychiatric illnesses and disorders.

PMID- 14679857
TI  - [Advances in neuroimaging in schizophrenia: magnetic resonance spectroscopy].
AB  - In the last decade magnetic resonance spectroscopy (MRS) has become an important
      tool to study CNS. In this paper authors present the basic principles of
      phosphorus and proton MRS and describe the results reported in schizophrenia.
      Studies indicate changes in membrane and cellular metabolism in CNS and are
      contribution in understanding neurochemical pathology of this disorder.

PMID- 14679858
TI  - [Periodontal disease and atherosclerosis: an underestimated link?].
AB  - Periodontal disease is a common bacterial and destructive disorder of oral
      tissues. We reviewed epidemiological and experimental to data studies
      demonstrating close associations between chronic periodontitis and development of
      generalized inflammation, vascular endothelial injury, and atherosclerosis.
      Periodontal disease has been convincingly emerging as an important independent
      cardiovascular risk factor. It deserves timely treatment also as a likely part of
      primary prevention of ischemic heart disease, stroke, and peripheral vascular
      disease.

PMID- 14679859
TI  - [Advances in diagnosis of facial nerve paralysis: pathophysiology and clinical
      symptoms].
AB  - Facial palsy is important clinical and social problem because of frequently
      appearance and to cause facial symmetry troubles which are visible for
      surroundings. Clinical picture of facial palsy, independently of its reason,
      contains a lot of symptoms depending on degree and place of nerve damage. The
      most visible and unpleasant for sick person unpleasant symptoms are abolition (in
      palsy) or considerably handicap (in paresis) function of facial countenance
      muscles which are hard to endure for patients. In special accidents patients
      demand psychology consultation and antidepression treatment to modify imagination
      about role of appearance in shape social relation. In place of damage nerve for
      particular attention deserve objective treatment the stapedius muscle reflex. It
      allows to objective estimation the facial nerve damage. Regress in paresis of
      this nerve decides on treatment. This treatment has a prognostic sense too-
      return of the stapedius muscle reflex announces return the function of damage
      nerve.

PMID- 14679860
TI  - [Glucocorticoids in the treatment of tuberculous pleurisy].
AB  - Glucocorticosteroids (GCS), as the inhibitors of inflammatory reaction in the
      pleura, may exert a favourable influence on the course of tuberculous pleurisy
      (TP). GCS applied as an adjuvant therapy to antituberculosis treatment accelerate
      the regression of symptoms and signs and absorption of pleural fluid in a
      significant percent of patients. The controlled trials of treatment with GCS
      failed to show, however, any significant advantages in comparison to placebo with
      respect to prevention of pleural adhesions or restrictive disturbances of
      ventilation. Pleural thickening is observed in more than half of the patients,
      independently of antituberculosis treatment regimen and adjuvant therapy with
      GCS. A reduction of respiratory disability can be achieved as a result of early
      initiation of respiratory physiotherapy programme, even before completion of
      evacuation of pleural fluid. In the treatment of TP the same regimen is applied
      as in chemotherapy of pulmonary tuberculosis, although a tendency is observed for
      reduction of the number of antituberculosis drugs administered in combination.
      Nowadays, with increasing efficacy of antituberculosis chemotherapy, application
      of GCS is limited to selected cases of TP (mainly complicated by toxaemia and/or
      respiratory failure).

PMID- 14679861
TI  - [The role of viruses in the pathogenesis of obstructive lung diseases].
AB  - Viral infections, especially recurrent viral infections in childhood are a well
      known risk factor of bronchial hyperresponsiveness and the development of asthma
      and COPD. The aim of this review was description of the possible role of viruses
      in the pathogenesis of obstructive lung diseases. Even though a lot of mechanisms
      in which viruses induce asthma and obstructive lung disease remain unclear, the
      role of viruses seems to be undeniable. Respiratory syncytial virus--a common
      cause of childhood bronchiolitis--is a risk factor for the development of atopy,
      asthma and allergy. The risk is increased in children with familial history of
      asthma. The reason is that RSV stimulates Th2 pattern of immune response, which
      is similar to inflammation, found in asthmatic patients. A significant role in
      the pathogenesis of COPD is related to recurrent viral infections that may be the
      answer why CD8+ cells predominate in bronchial inflammation in patients with
      COPD. Latent adenoviral infection is probably important in the pathogenesis of
      obstructive disease. The E1A region of adenoviral genome and adenoviral E1A
      protein can be found in epithelial cells long after acute infection resolves. It
      is well known that in patients with COPD, E1A protein can be detected more often
      than in healthy subjects and it is responsible for amplifying the response to
      cigarette smoke and inducing steroid resistance.

PMID- 14679862
TI  - [Arterial hypertension as a complication and risk factors of progression of
      chronic renal failure in children].
AB  - Arterial hypertension is both a complication of chronic renal failure (crf) and
      one of the main risk factors of progression of crf. Investigations led in last 20
      years enabled discovery of self-perpetuating mechanisms of crf progression and
      explained the role of arterial hypertension as one of the main risk factors of
      progression to end stage renal disease. Proposed in 80-ies and 90-ies years of XX
      th century theories of hyperfiltration and proteinuria toxicity became the basis
      for renoprotective therapy in crf. Despite lack of large clinical trials held in
      children with crf, the principles of renoprotection in children with crf are also
      proposed. The relation between blood pressure, proteinuria and progression of crf
      is causing that concerning crf patients, term "hypotensive therapy" more often is
      replaced by the term "renoprotective therapy".

PMID- 14679863
TI  - [Rational choice of pharmaceutical products].

PMID- 14679864
TI  - John M. Eisenberg Patient Safety Awards. Individual lifetime achievement: Jeffrey
      B. Cooper, Ph.D., Massachusetts General Hospital. Interview by Steven Berman.

PMID- 14679865
TI  - John M. Eisenberg Patient Safety Awards. The Leapfrog Group for Patient Safety:
      rewarding higher standards.
AB  - BACKGROUND: The Leapfrog Group is a consortium of more than 145 large health care
      purchasers committed to a common set of purchasing principles through which to
      leverage dramatic improvements in the safety, quality, and overall value of
      health care. Leapfrog purchasers mobilize consumers to seek out higher-quality
      providers, and they reward higher-quality providers. Leapfrog is primarily
      operationalized through Regional Roll-Outs--locally led purchaser efforts.
      PATIENT SAFETY RECOMMENDATIONS: The Leapfrog Group purchasers first focused on
      three patient safety practices, or "safety leaps," to reduce preventable medical
      errors--computer physician order entry, evidence-based hospital referral, and
      intensive care unit (ICU) physician staffing. Leapfrog's leaps are refined and
      updated annually on the basis of evidence and input from experts in the field.
      IMPACT ON PATIENT SAFETY: On the basis of survey results from the first 22
      Regional Roll-Outs, as of September 2003, 4% of 633 hospitals reporting from the
      22 regions fully met the CPOE standard, and an additional 17% of the 633 said
      they would meet the standard by 2005. Survey results also showed that 22% of the
      605 hospitals in the 22 regions with ICUs met Leapfrog's ICU staffing
      recommendations and that an additional 5% would meet the standard by 2004. NEXT
      STEPS: In 2004 Leapfrog will launch new Regional Roll-Outs, bringing Leapfrog
      consumer education, hospital-specific information, and purchasing strategies to
      more communities nationwide.

PMID- 14679866
TI  - John M. Eisenberg Patient Safety Awards. The LVHHN patient safety video: patients
      as partners in safe care delivery.
AB  - BACKGROUND: In fall 2002, Lehigh Valley Hospital and Health Network (LVHHN), an
      800-bed, three-site academic community hospital, embarked on an initiative to
      produce an educational patient safety video. IMPLEMENTING THE INITIATIVE: The
      video addresses six topics relevant to optimum patient safety: treatment plan,
      medication safety, falls, surgical site identification, hand washing, and
      discharge planning. Each segment outlines strategies that patients may employ or
      observations they should make to improve patient safety. RESULTS: Analysis of the
      patient survey data, which were based on 217 surveys, indicated that patients
      felt more comfortable talking with their health care workers about questions or
      concerns after viewing the video and that they rated their knowledge of patient
      safety higher. Patients generally rated the six sections as helpful. DISCUSSION:
      The video was intended to become an important step in the preadmission process.
      Releasing the video to patients and staff helped to normalize some practices that
      initially were not comfortable for staff (repeatedly asking an inpatient for his
      or her name and date of birth before administering all medications) or patients
      (inquiring whether a staff member has washed his or her hands). Additional
      methods were in development to share the video with current and prospective
      patients and assess its impact. The LVHHN patient safety council plans to share
      the video with the community at large.

PMID- 14679867
TI  - John M. Eisenberg Patient Safety Awards. Safety, effectiveness, and efficiency: a
      Web-based virtual anticoagulation clinic.
AB  - BACKGROUND: Information systems that include Web-based technology can provide
      clinical decision support in care processes that can be algorithmically
      described. Long-term oral anticoagulation with warfarin is one such care process.
      THE VIRTUAL ANTICOAGULATION CLINIC: A clinical decision support tool was
      developed using evidence-based guidelines from the extant medical literature on
      the indications for and management of therapy with warfarin. Training modules for
      physicians and support staff were implemented, and patients were prospectively
      enrolled in the "virtual anticoagulation clinic" when they began taking warfarin
      or when they returned for routine follow-up under the usual care model.
      Designated warfarin coordinators managed the virtual anticoagulation clinic under
      physician supervision. RESULTS: Following the adoption of the virtual
      anticoagulation clinic, uniform improvement in time in therapeutic range was
      observed in each participating practice, with those practices using it the
      longest equaling or exceeding results reported from formally organized warfarin
      clinics. Major adverse events were observed only in patients who were not managed
      in the manner suggested by the virtual anticoagulation clinic. CONCLUSIONS: A Web
      based solution to chronic anticoagulation therapy offers an inexpensive, safe,
      and significantly more effective alternative to the usual care model.

PMID- 14679868
TI  - Reduction in patient enrollment in the Veterans Health Administration after media
      coverage of adverse medical events.
AB  - BACKGROUND: Health care organizations may experience costs associated with
      preventable adverse events in the form of poor brand image and subsequent patient
      disenrollment. A retrospective cohort design was used to determine whether media
      coverage of adverse events that occurred in Veterans Health Administration (VHA)
      hospitals was associated with subsequent veteran disenrollment. METHODS: Twenty
      four newspaper reports of medical adverse events that occurred between 1994 and
      1999 within the VHA system were identified. Regionally adjusted changes in
      enrollment rates for VHA facilities that had reported adverse events were
      compared with those that had not one year before and one and three years after
      publication of the newspaper reports. RESULTS: Facilities that had published
      reports of adverse events had lower enrollment rates after publication of the
      report for two groups of veterans. CONCLUSIONS: Within the VHA system, health
      care organizations involved in adverse events that generated publicity suffered a
      greater rate of patient disenrollment. If safe patient care practices can reduce
      adverse publicity, they may enhance corporate value by maintaining enrollment of
      the patient population.

PMID- 14679869
TI  - Addressing patients' emotional and spiritual needs.
AB  - BACKGROUND: A comprehensive, systematic literature review and original research
      were conducted to ascertain whether patients' emotional and spiritual needs are
      important, whether hospitals are effective in addressing these needs, and what
      strategies should guide improvement. METHODS: The literature review was conducted
      in August 2002. Patient satisfaction data were derived from the Press Ganey
      Associates' 2001 National Inpatient Database; survey data were collected from
      1,732,562 patients between January 2001 and December 2001. RESULTS: Data analysis
      revealed a strong relationship between the "degree to which staff addressed
      emotional/spiritual needs" and overall patient satisfaction. Three measures most
      highly correlated with this measure of emotional/spiritual care were (1) staff
      response to concerns/complaints, (2) staff effort to include patients in
      decisions about treatment, and (3) staff sensitivity to the inconvenience that
      health problems and hospitalization can cause. DISCUSSION: The emotional and
      spiritual experience of hospitalization remains a prime opportunity for QI.
      Suggestions for improvement include the immediate availability of resources,
      appropriate referrals to chaplains or leaders in the religious community, a team
      dedicated to evaluating and improving the emotional and spiritual care
      experience, and standardized elicitation and meeting of emotional and spiritual
      needs. Survey data suggested a focus on response to concerns/complaints,
      treatment decision making, and staff sensitivity.

PMID- 14679870
TI  - Get creative to boost adherence in disadvantaged populations.

PMID- 14679871
TI  - Treating dyspepsia: new OTC drug changes the economic picture.
AB  - Uninvestigated dyspepsia is very common, and it can be caused by peptic ulcer
      disease. However, just when patients should undergo expensive tests to determine
      the cause of their symptoms is not always clear-cut--particularly now that an OTC
      proton pump inhibitor (PPI) is available. Get some expert advice on what factors
      to consider when treating these patients.

PMID- 14679872
TI  - Clinical guidelines: strategies to nurture acceptance and adherence.
AB  - Evidence-based guidelines are a cornerstone of effective DM, and in many cases,
      they end up in the garbage or collecting dust. DMA investigated why physicians
      are so often loath to implement new guidelines, and what types of strategies are
      successfully overcoming these barriers.

PMID- 14679873
TI  - Simple three-item screen offers efficient way to identify migraine in primary
      care.
AB  - It's a problem that is commonly overlooked by PCPs--despite the fact that
      migraine costs employers billions each year in absenteeism and lost productivity.
      Additionally, migraine sufferers often must deal with substantial pain and
      disability even though there are highly effective treatments available. Now, a
      new self-administered tool has been validated that can identify migraine with
      just three simple questions. Get the details.

PMID- 14679874
TI  - ASAE's Ergonomics, Safety, and Health Division--cosmetics or real progress?

PMID- 14679875
TI  - Use of the North American guidelines for children's agricultural tasks with Hmong
      farm families.
AB  - This literature review synthesizes available studies on Hmong agricultural
      practices, patterns of childhood growth and development of Hmong children in the
      context of injury prevention, and potential application or adaptation of the
      North American Guidelines for Children's Agricultural Tasks (Lee and Marlenga,
      1999) for Hmong children working in the U.S. Data from qualitative interviews,
      focus groups, case studies, and surveys were collected, categories were
      determined, and themes were identified. Field tools and practices, gender roles,
      and reasons for farming were examined, as well as physical and cognitive
      development of Hmong children and Hmong parenting techniques to describe factors
      related to farm task assignment of children. Current agricultural practices of
      Hmong in the U.S. can be described as generally small-scale operations that use
      mainly hand tools, manual labor, and local direct-marketing techniques. Specific
      practices include thinning, weeding, and hoeing; carrying tools, buckets, or
      baskets; setting plant supports; and watering. Hmong children appear to be given
      greater amounts of responsibility at earlier ages than North American children.
      Hmong parenting practices, as would be used in task assignment, are somewhat more
      authoritarian-based and lead to psychosocial skills that are more group-oriented
      than individual-oriented. Hmong children were found to be shorter than children
      in the U.S. of the same ages. This review suggests that the NAGCAT cannot be
      literally translated and disseminated to Hmong farming families as an injury
      prevention intervention. Further information is needed about what farm tasks
      Hmong children do and how Hmong parents assign those tasks to children.

PMID- 14679876
TI  - Observation study of students who completed a high school agricultural safety
      education program.
AB  - The Agricultural Disability Awareness and Risk Education Project (AgDARE) is a
      research-based curriculum of agricultural safety instruction based on Prochaska
      and DiClemente's Transtheroetical Model of Change. The program uses eight reality
      based psychomotor and narrative modules to teach safe farm work behaviors. In
      addition to in-class pencil and paper assessments on safety attitudes and
      behavior intention, farm visits were made to assess the longer term influence of
      AgDARE. Visits were made between 11 and 20 months (mean = 14.24 months) after
      completion of the classroom instruction to 29 students who worked on farms and
      completed at least one-half of the AgDARE instruction. All but one of the visited
      students exhibited safe work behaviors addressed by the AgDARE instruction. In
      addition, 76% of the visited students had made positive changes in their farm
      work behavior since participating in AgDARE. Changes extended beyond the
      instruction that students received in class to include other aspects of farm work
      and other family members. The use of farm visits to evaluate students' safety
      behaviors was tempered by the challenge of contacting students and obstacles
      associated with observing work in an environment where little is routine or
      regular.

PMID- 14679877
TI  - Hydrogen sulfide assessment in shallow-pit swine housing and outside manure
      storage.
AB  - In Saskatchewan, some recent incidents have lead us to believe that certain
      manure management activities can potentially release high concentrations of H2S
      into the atmosphere of shallow-pit barns. The objectives of the monitoring
      project reported here were to evaluate worker exposure to H2S during the
      completion of the following tasks: emptying of in-barn shallow manure pits, power
      washing of barn rooms, and agitation and emptying of outdoor manure storage
      facilities. In-barn monitoring was performed in gestation, farrowing, nursery,
      and grow-finish sections in the summer of 2001 and the winter of 2002 on four
      different farms. Plug pulling can generate very high concentrations of H2S. The
      maximum values recorded during some of the monitored events reached 1,000 ppm.
      The H2S released as a plug is being pulled does not follow a predictable pattern
      when considering the level that will be reached, the concentration variations
      during the event, and the time at which the peak concentration will be observed.
      Power washing generated lower H2S concentrations than plug pulling. However, as
      the task to be performed generally takes time, the 15 min time-weighed average of
      15 ppm (STEL) can be reached after the task started and can be exceeded for a
      long period of time, which for some of the monitored events was more than 30 min.
      Finally, monitoring at the storage facilities showed that the risks of exposure
      to excessive H2S concentrations during the agitation and emptying of outside
      manure storage facilities were very limited. Results from this study suggest that
      pig production buildings involving short-term storage of liquid manure may
      present H2S exposure risks that have been underestimated until now. All workers
      should be provided with an H2S monitor and safety equipment to ensure that
      workers are protected when the H2S concentration rises. As well, engineering
      controls have to be developed to prevent H2S formation in the manure or H2S
      emission into the worker/pig space.

PMID- 14679878
TI  - A community-based telephone survey of work and injuries in teenage agricultural
      workers.
AB  - In order to estimate the one-year cumulative incidence of work-related injuries
      in teenage agricultural workers and to characterize the patterns and types of
      agricultural work performed by teenagers, we performed a community-based random
      digit dialing telephone survey. We used a sampling frame of farm and non-farm
      households to access information on teenage agricultural workers. An agricultural
      community in eastern Washington State was selected due to the high number of
      teenage youth and its agricultural economy. Teenage agricultural workers who
      worked for an agricultural business owned by one of their family members were
      more likely to work a greater number of seasons, work fewer hours per week,
      perform tasks involving driving, animal care, and mechanic work, and were less
      likely to be seasonal workers or work in the harvest than teenagers who did not
      work for a family member. A similar pattern of work differences was seen when
      comparing non-Hispanic to Hispanic agricultural workers. Teenagers working for a
      family member in agriculture had a higher injury rate than teenagers working for
      an agricultural business not owned by a family member. The injury rate among
      Hispanic teenage agricultural workers was also higher than that of non-Hispanics.

PMID- 14679879
TI  - Fatal injuries in Finnish agriculture, 1988-2000.
AB  - Agriculture is one of the most hazardous industries in Finland. The aim of this
      study was to describe and analyze fatal farm injuries in Finland in 1988 to 2000.
      The information regarding farm-related fatalities was collected by the Kuopio
      Regional Institute of Occupational Health. The material of this study consisted
      of all fatal injuries that occurred on a farm or away from a farm in the course
      of agricultural work. A total of 217 farm-related fatalities occurred in Finland
      between 1988 and 2000. Of these, 120 were tractor-related, and 97 were other
      fatal farm injuries. Most of the injuries involved middle-aged or older male
      farmers. The most typical fatalities with tractors were tractor overturns during
      driving on a road or working in a field. Other fatal farm incidents occurred
      mainly in construction work, animal husbandry, or forest work. Elderly farmers
      and children proved to be risk groups for fatal injuries.

PMID- 14679881
TI  - Evaluating the intangibles: assessing a candidate's potential.

PMID- 14679880
TI  - Farmers' perceptions and concerns: the risks of driving farm vehicles on rural
      roadways in North Carolina.
AB  - This study focuses on farmers' perceptions of roadway safety and reviews specific
      and pertinent North Carolina rural road crash data to evaluate their perceptions
      and concerns. A survey was mailed to 1,357 prospective participants throughout
      North Carolina. Of these, 656 (48.3%) North Carolina farmers completed and
      returned the survey. The study revealed that while the majority of respondents
      took a number of specific safety measures to ensure their safety while driving
      their tractor on rural roads, most believed that driving their tractor on rural
      roads was more dangerous than it was five years ago. Few respondents believed
      that laws governing tractors on rural roads are well known by urban residents.
      While a majority of the respondents would support a law to mandate the use of a
      slow-moving vehicle (SMV) emblem on the back of slow-moving farm equipment, a
      majority also believed that a more effective way to mitigate potential crashes
      would be to ensure that all farm vehicles had blinking or flashing lights, that
      diamond-shaped caution signs depicting a tractor were posted on roadways with
      frequent tractor traffic, and that roadway shoulders were created or widened on
      roads with heavy farm traffic so that tractors could move off the roadway. Only
      22% of respondents felt safe driving their tractor on rural roadways in North
      Carolina. Most respondents felt that the biggest problem with roadway safety was
      the lack of respect and increased speed of other drivers. Recent data indicate
      that in crashes involving farm vehicles, citations were issued to 34% of the non
      farm vehicle operators and 24% to farm vehicle operators. For those driving non
      farm vehicle who were deemed at fault, 66% were cited for failure to reduce
      speed. For those driving farm vehicles, the most frequent citation involved the
      lack of safe movement.

PMID- 14679882
TI  - A formal, standardized and evidence-based approach to Chest Pain Center
      development and process improvement: the Society of Chest Pain Centers and
      Providers accreditation process.
AB  - The notion of a Chest Pain Center has continued to develop over the past twenty
      years. The designation of "Chest Pain Center" now applies to the entire facility,
      much the same as that of "Trauma Center." The Chest Pain Center model
      incorporates both operational and clinical considerations required to develop
      proper Acute Coronary Syndrome (ACS) care in the context of a complex health-care
      system. The Society of Chest Pain Centers and Providers has launched a Chest Pain
      Center Accreditation initiative that provides an organizational road map for
      success in approaching the care for patients with ACS.

PMID- 14679883
TI  - Using performance improvement strategies to reduce and prevent medication errors.
      1.
AB  - The headlines feature tragic stories describing errors in medical practice.
      Medical literature reveals that errors in medical practice are common. In 1999,
      the Institute of Medicine released its report. "To Err is Human," that detailed
      an estimated 44,000 to 98,000 deaths annually due to medical errors. In September
      of 2002, the Archives of Internal Medicine released a study of medication errors
      observed in 36 healthcare facilities. Medication errors were commonly occurring
      in 19% or nearly one error out of every five doses administered in a typical
      hospital. It is imperative to analyze patient safety issues related to medication
      administration. This paper presents methods to improve the quality of care
      delivered by: Building effective structures through efficient use of technology.
      Establishing improved process through collaboration and teamwork. Measuring and
      reporting performance outcomes.

PMID- 14679885
TI  - ["Diabetes mellitus"].

PMID- 14679884
TI  - Maximizing the quality and cost-effectiveness of cardiac care with laboratory
      technology and process improvements.

PMID- 14679886
TI  - [Drug treatment of type 2 diabetes].
AB  - Diabetes mellitus and its complications constitute a major health problem in
      modern societies. The disease affects approximately 5% of the adult population in
      western countries. The underlying process of the metabolic disorder is a defect
      in insulin secretion, insulin action, or both. Weight reduction, calorie
      restriction and patient education remain the cornerstones of the management of
      type 2 diabetes. When lifestyle modification fails to maintain adequate glycaemic
      control, insulin or oral hypoglycemic agents are typically used to manage the
      disease. The currently available five classes of oral agents differ in mechanism
      and duration of action, the degree to which they lower blood glucose and their
      side-effect profile. For most of these antiglycaemic agents, there is a lack of
      evidence on the effects on long-term complications. Only metformin has clearly
      proved that it can reduce mortality in obese patients with type 2 diabetes. Human
      insulin reduces acute and long-term mortality in patients with CVD. Furthermore,
      intensive treatment either with insulin or sulfonylurea has proved that it can
      prevent microvascular complications in type 2 diabetes. Additional randomized
      controlled trails assessing hard clinical endpoints are needed to better inform
      patients and enable physicians to establish optimal treatment strategies.

PMID- 14679887
TI  - [Empowerment in diabetes mellitus: theory and practice].
AB  - Since 1989 the concept of empowerment and the promotion of self-care management
      have been generally proposed for Diabetes care. The bio-psycho-social concept of
      empowerment aims at encouraging the patient to develop self-care management for
      Diabetes treatment that is evidence-based and in accordance with the patient's
      goals and life style. It therefore promotes the patient's autonomy. With regard
      to HbA1c and life-quality parameters, it has been proven to be effective.
      Prerequisites for implementing empowerment as therapeutic intervention are:
      interest in the individual reality of the patient, a patient-centred
      communication style and an adequate time management. In this article we describe
      the theoretical aspects of the concept of empowerment and propose practical
      recommendations for the empowerment of patients suffering from Diabetes mellitus.

PMID- 14679888
TI  - [Diabetes and drug treatment of hypertension].
AB  - In hypertensive diabetic patients, reducing blood pressure is among the best
      evaluated and most effective interventions for lowering mortality and morbidity.
      First line antihypertensive agents are: chlorthalidone or other thiazide-type
      diuretics, beta-blockers and ACE-inhibitors. In type 2 diabetic patients with
      left ventricular hypertrophy, the ARB Cosaar has been proven to be effective. To
      achieve an effective blood pressure reduction, a combination of different
      antihypertensive agents is necessary for most patients. Specially structured
      patient education programmes are another effective means of achieving this goal.

PMID- 14679889
TI  - [Diabetes and lipids].
AB  - Dyslipidemia is one of the major cardiovascular risk factors especially for
      patients with type 2 diabetes mellitus. As a feature of the metabolic syndrome
      insulin resistance is also associated with an atherogenic lipoprotein phenotype.
      In type 1 diabetes inadequate glycemic control results in an increase of plasma
      triglyceride levels. The treatment of diabetic dyslipidemia is based on an
      improvement of glycemic control, in type 1 and type 2 diabetes, as well as in
      lifestyle recommendations, including dietary advice and physical exercise. The
      achievement of strict target levels, especially LDL-cholesterol values below 100
      mg/dL, requires lipid lowering drug therapy. This LDL-cholesterol target level is
      based on the fact that diabetic patients reveal the same risk for myocardial
      infarction as non-diabetics after their first cardiovascular event. Thus the
      diagnosis of diabetes is regarded as an equivalent for manifest cardiovascular
      disease. The re-evaluation of large lipid intervention trials (4 S, CARE, LIPID,
      VA-HIT, Heart Protection Study) could clearly demonstrate also for the diabetic
      subpopulation that statin and fibrate therapy results in a significant reduction
      of the cardiovascular risk.

PMID- 14679890
TI  - [Diabetic foot syndrome].
AB  - The diabetic foot syndrome (DFS) is an important diabetic complication. The
      typical lesion is a neuropathic plantar foot ulcer which heals well when treated
      properly. However, complications resulting from deep infections of soft tissue or
      bone, together with a reduced peripheral blood flow, may necessitate amputation
      of the lower limbs. In general, diabetic patients have a 10-fold higher risk for
      amputation than non-diabetic subjects and also a poorer long-time prognosis than
      the latter. The target of a 50% reduction of lower limb amputations in diabetic
      patients, given by the St. Vincent Declaration for Europe in 1990, has not been
      achieved. The prevention as well as treatment of DFS have to be improved in order
      to achieve this target. The feet of diabetic patients must be inspected regularly
      and the patients must be educated appropriately. Detailed information on
      avoidable risk factors and the availability of protective footwear are essential
      for the prevention of DFS. An increasing number of ischemic diabetic subjects
      undergo vascular reconstruction, which yields good results. On account of the
      multifactorial etiology of DFS, a multidisciplinary approach is required to
      resolve the problem. In addition to a diabetologist, the team should include a
      plastic and vascular surgeon, a neurologist, a radiologist and an orthopedist.

PMID- 14679891
TI  - [Gestational diabetes].
AB  - Gestational diabetes (GDM) is defined as any degree of glucose intolerance with
      onset or first recognition during pregnancy. GDM is becoming an increasing health
      problem worldwide and one of the most common complications of pregnancy. The
      prevalence of GDM in Central Europe is 5-7%. GDM is associated with increased
      feto-maternal morbidity as well as long-term complications in mothers and
      offspring. The key symptom of GDM is the development of diabetic fetopathy. Fetal
      hyperinsulinism is associated with macrosomia and a higher rate of birth injuries
      and caesarean sections, neonatal hypoglycemia, respiratory distress and due to
      fetal programming the development of the sequelae of the metabolic syndrome in
      childhood or adolescence. GDM is commonly diagnosed by an oral glucose tolerance
      test (OGTT) between gestational weeks 24 and 28. In addition, in case of a high
      risk of GDM (history of poor obstetric outcome: stillbirth, congenital
      malformation, birth weight > or = 4500 g or a history of impaired glucose
      tolerance or impaired fasting glucose) impaired glucose metabolism or diabetes
      should be excluded in the first trimester. GDM shares the same pathophysiology
      and clinical signs as diabetes mellitus type 2. Thus maternal obesity, higher
      age, hypertension as well as a positive family history of type 2 diabetes are
      high risk factors for the development of GDM. If GDM is diagnosed, a strict
      metabolic control is mandatory. All women should receive nutritional counseling
      and be instructed in blood glucose self-monitoring. If blood glucose levels
      cannot be maintained in the normal range (fasting < 95 mg/dl and 1 h after meals
      < 130 mg/dl), insulin therapy should be initiated. Maternal and fetal monitoring
      is required in order to minimize maternal and fetal/neonatal morbidity and
      perinatal mortality. After delivery, all women with GDM have to be reevaluated as
      to their glucose tolerance by a 75 gOGTT (WHO criteria). While 85% of these women
      will return to normal glucose tolerance 8 weeks postpartum, those with persisting
      impaired glucose tolerance are at particularly high risk for diabetes.

PMID- 14679892
TI  - [Preimplantation diagnosis (PID) in humans from the clinical viewpoint].
AB  - This paper describes the current status of preimplantation diagnosis from the
      viewpoint of an experienced clinician specialized in reproductive medicine.
      Current progress and international experience with different applications and
      techniques are reviewed on the basis of the literature. Particular interest is
      focused on possible advantages of routinely diagnosing major chromosome
      aneuploidies in preimplantation-embryos of patients undergoing in vitro
      fertilization and embryo transfer. Last but not least, a short survey of the
      international guidelines and legislation is compared to the situation in Austria
      where it is currently unclear whether preimplantation diagnosis is allowed or
      not.

PMID- 14679893
TI  - [Preimplantation diagnosis--a routine examination?].
AB  - The discussion on pre-genetic diagnosis continues. The question is whether it
      should be allowed in Austria and Germany, too. Pre-geneticdiagnosis aims at
      examining embryos for possible genetic damage prior to implantation. The method
      of producing embryos in vitro (IVF) primarily served to enable hitherto childless
      couples to become parents. Currently, however, application is moving towards
      helping couples capable of natural fertilisation but at higher risk of producing
      a handicapped child. Here, embryos are created in vitro, examined and only
      implanted if in good health. The damaged embryos, however, are destroyed. Some
      argue that this form of selection is no different to the termination of pregnancy
      in an abortion, and furthermore the PID is the more gentle method. These
      arguments are discussed in this article, and in addition whether the principle of
      preserving human dignity is already valid for the embryo and whether a doctor is
      authorized to produce, select and kill human life.

PMID- 14679894
TI  - [Conjugation in bacilli].
AB  - The review considers experimental data on the conjugal transfer of plasmids in
      the Bacillus cereus and Bacillus subtilis groups (the transfer of large self
      transmissible plasmids and the mobilization of small plasmids). Conjugation in
      bacilli is compared with conjugation in E. coli dependent on the F factor.
      Conjugation of bacilli in their natural habitats is also discussed.

PMID- 14679896
TI  - [Oxidative stress and antioxidant cell protection systems in the microaerophilic
      bacterium Spirillum winogradskii].
AB  - The influence of oxygen availability during cultivation on the biosynthetic
      processes and enzymatic activities in the microaerophilic bacterium Spirillum
      winogradskii D-427 was studied, and the roles played by different systems of the
      defense against oxidation stress were determined. The metabolic adjustments
      caused by transition from microaerobic (2% O2) aerobic conditions (21% O2 of the
      gas phase) were found to slow down constructive metabolism and increase synthesis
      of exopolysaccharides as a means of external protection of cells from excess
      oxygen. This resulted in a twofold decline of the growth yield coefficient. Even
      though the low activity of catalase is compensated for by a multifold increase in
      the activities of other cytoplasmic enzymes protecting from toxic forms of O2-
      peroxidase and enzymes of the redox system of glutathione (glutathione peroxidase
      and glutathione reductase)--massive lysis of cells starts in the mid-exponential
      phase and leads to culture death in the stationary phase because of H2O2
      accumulation in the periplasm (up to 10 micrograms/mg protein). The absence in
      cells of cytochrome-c-peroxidase, a periplasmic enzyme eliminating H2O2, was
      shown. It follows that the major cause of oxidative stress in cells is that
      active antioxidant defenses are located in the cytoplasm, whereas H2O2
      accumulates in the periplasm due to the lack of cytochrome-c-peroxidase. The
      addition to the medium of thiosulfate promotes elimination of H2O2, stops cell
      lysis under aerobic conditions, lends stability to cultures, and results in a
      threefold increase in the growth yield.

PMID- 14679895
TI  - [Free radicals in mercury-resistant bacteria indicate a novel metabolic pathway].
AB  - A mercury resistant-soil bacterium P.10.15, identified as a close relative of
      Pseudomonas veronii, was shown to accumulate a specific compound in the
      stationary phase of growth. This compound is converted to a long-lived free
      radical under oxidizing conditions, as registered by its EPR signal at room
      temperature. The compound was purified by ion-exchange and gel-filtration
      chromatography and identified by mass spectroscopy, 2D NMR, and EPR as a
      trisaccharide beta-D-GlcpNOH,CH3-(1-->6)-alpha-D-Glcp-(1-->1)-alpha-D-Glcp, or,
      in other words, as 6-O-(2-deoxy-2-[N-methyl]hydroxylamino-beta-D- glucopyranosyl)
      alpha-alpha-trehalose, previously discovered in Micrococcus luteus
      (lysodeikticus) and named lysodektose. The compound is suggested to be a novel
      intermediate of a previously unknown basic metabolic pathway of trehalose
      transformation in bacteria, a potential target for antibacterial drug
      development.

PMID- 14679897
TI  - [The status and the role of glutathione under disturbed ionic balance and pH
      homeostasis in Escherichia coli].
AB  - The study of glutathione status in aerobically grown Escherichia coli cultures
      showed that the total intracellular glutathione (GSHin + GSSGin) level falls by
      63% in response to a rapid downshift in the extracellular pH from 6.5 to 5.5. The
      incubation of E. coli cells in the presence of 50 mM acetate or 10 micrograms/ml
      gramicidin S decreased the total intracellular glutathione level by 50 and 25%,
      respectively. The fall in the total intracellular glutathione level was
      accompanied by a significant decrease in the (GSHin:GSSGin) ratio. The most
      profound effect on the extracellular glutathione level was exerted by gramicidin
      S, which augmented the total glutathione level by 1.8 times and the
      (GSHout:GSSGout) ratio by 2.1 times. The gramicidin S treatment and acetate
      stress inhibited the growth of mutant E. coli cells defective in glutathione
      synthesis 5 and 2 times more severely than the growth of the parent cells. The pH
      downshift and the exposure of E. coli cells to gramicidin S and 50 mM acetate
      enhanced the expression of the sodA gene coding for superoxide dismutase SodA.

PMID- 14679898
TI  - [The effect of sodium malonate on yeast thermotolerance].
AB  - The study of the effect of malonate (an inhibitor of the succinate dehydrogenase
      complex of the respiratory chain of mitochondria) on the thermotolerance of the
      fermentative Saccharomyces cerevisiae and nonfermentative Rhodotorula rubra
      yeasts showed that malonate augmented the damaging effect of heat shock on the
      yeasts utilizing glucose (or other sugars) by means of oxidative phosphorylation.
      At the same time, malonate did not influence and sometimes even improved the
      thermotolerance of the yeasts utilizing glucose through fermentation. The
      suggestion is made that cell tolerance to heat shock depends on the normal
      functioning of mitochondria. On the other hand, their increased activity at
      elevated temperatures may accelerate the formation of cytotoxic reactive oxygen
      species and, hence, is not beneficial to cells.

PMID- 14679899
TI  - [Activity of the enzymes of carbon metabolism in Sulfobacillus sibiricus under
      various conditions of cultivation].
AB  - The thermoacidophilic iron-oxidizing chemolithotroph Sulfobacillus sibiricus N1T
      is characterized by steady growth and amplified cell yield when grown in
      vigorously aerated medium containing Fe2+, glucose, and yeast extract as energy
      sources. In this case, carbon dioxide, glucose, and yeast extract are used as
      carbon sources. Glucose is assimilated through the fructose-bisphosphate pathway
      and the pentose-phosphate pathway. Glyoxylate bypass does not function in S.
      sibiricus, and the tricarboxylic acid cycle is disrupted at the level of 2
      oxoglutarate dehydrogenase. The presence of ribulose-bisphosphate carboxylase
      indicates that carbon dioxide fixation proceeds through the Calvin cycle. The
      activity of ribulose-bisphosphate carboxylase is highest in autotrophically grown
      cells. The cells also contain pyruvate carboxylase, phosphoenolpyruvate
      carboxylase, phosphoenolpyruvate carboxykinase, and phosphoenolpyruvate
      carboxytransphosphorylase.

PMID- 14679900
TI  - [Carbohydrate metabolism of the Saccharolytic alkaliphilic anaerobes Halonatronum
      saccharophilum, Amphibacillus fermentum, and Amphibacillus tropicus].
AB  - The saccharolytic anaerobic bacteria Halonatronum saccharophilum, Amphibacillus
      fermentum, and Amphibacillus tropicus produce formate the main fermentation
      product. In the alkaliphilic community, formate is used as the preferential
      substrate for sulfate reduction. To reveal the pathways of carbohydrate
      fermentation by these bacteria, the activity of the key enzymes of carbohydrate
      metabolism and their pH dependence was studied. It was established that H.
      saccharophilum utilized glucose by the fructose bisphosphate and hexose
      monophosphate pathways, and A. tropicus, by the fructose bisphosphate and Entner
      Doudoroff pathways. The activity of the key enzymes of all three pathways of
      glucose metabolism was detected in Amphibacillus fermentum. According to the data
      obtained, the glucose catabolism in H. saccharophilum. A. fermentum, and A.
      tropicus mainly proceeds via the fructose bisphosphate pathway. The pH optima of
      the key enzymes of the glucose metabolism of the alkaliphiles are shifted to
      alkaline values. In A. tropicus, formate is formed from pyruvate under the action
      of pyruvate formate-lyase; and in the haloanaerobe H. saccharophilum, formate
      dehydrogenase is involved in formate metabolism.

PMID- 14679901
TI  - [The biological activity of the Sinorhizobium meliloti glucan].
AB  - The study of the effect of the periplasmic glucan isolated from the root-nodule
      bacterium S. meliloti CXM1-188 on the symbiosis of another strain (441) of the
      same root-nodule bacterium with alfalfa plants showed that this effect depends on
      the treatment procedure. The pretreatment of alfalfa seedlings with the glucan
      followed by their bacterization with S. meliloti 441 insignificantly influenced
      the nodulation parameters of symbiosis (the number of root nodules and their
      nitrogen-fixing activity) but induced a statistically significant increase in the
      efficiency of symbiosis (expressed as the masses of the alfalfa overground parts
      and roots). At the same time, the pretreatment of S. meliloti 441 cells with the
      glucan brought about a considerable decrease in the nodulation parameters of
      symbiosis (the number of the root nodules and their nitrogen-fixing activity
      decreased by 2.5-11 and 7 times, respectively). These data suggest that the
      stimulating effect of rhizobia on host plants may be due not only to
      symbiotrophic nitrogen fixation but also to other factors. Depending on the
      experimental conditions, the treatment of alfalfa plants with the glucan and
      their bacterization with rhizobial cells enhanced the activity of peroxidase in
      the alfalfa roots and leaves by 10-39 and 12-27%, respectively.

PMID- 14679902
TI  - [Membrane-bound forms of serine proteases of Bacillus intermedius].
AB  - Proteolytic proteins solubilized from the membrane of Bacillus intermedius were
      studied by electrophoresis. The content of membrane-bound proteinases was lower
      in cells grown in the presence of glucose. Proteinase enzymograms revealed four
      molecular forms of subtilisin and four molecular forms of glutamyl endopeptidase.
      The electrophoretic mobility of one of the molecular forms was similar to those
      of the mature extracellular proteinases. Chromatography of membrane proteins on a
      MonoS column yielded four protein fractions that caused hydrolysis of Z-Glu-pNA
      and four fractions that caused hydrolysis of Z-Ala-Ala-Leu-pNA, which is in
      agreement with the results of electrophoresis. The molecular forms of proteinases
      identified in the membrane may reflect various stages of biogenesis of the
      corresponding extracellular enzymes.

PMID- 14679903
TI  - [The production of antifungal metabolites by Pseudomonas chlororaphis grown on
      different nutrient sources].
AB  - It was found that the antifungal activity of Pseudomonas chlororaphis SPB1217 is
      due to phenazine-1-carboxylic acid, phenazine-1-carboxamide, and two unidentified
      exometabolites. The carbon source used for the growth of this bacterial strain
      and iron ions present in the medium considerably influenced the proportion
      between the antifungal metabolites. The maximum production of phenazines was
      observed in the media enriched in amino acids and iron ions. The absence of
      correlation between the production of phenazines and antifungal activity
      indicates that phenazines are not the only antifungal metabolites of the strain.
      Organic acids as nutrient sources provide for more intense production of
      exometabolites and for a higher level of antifungal activity than do sugars.

PMID- 14679904
TI  - [Plasmid profiles of Acidithiobacillus ferrooxidans strains adapted to different
      oxidation substrates].
AB  - Plasmid profiles were studied in five Acidithiobacillus ferrooxidans strains of
      various origin cultivated on medium with Fe2+, as well as adapted to such
      oxidation substrates as S0, FeS2, and sulfide concentrate. The method used
      revealed plasmids in all A. ferrooxidans strains grown on medium with Fe2+. One
      plasmid was found in strain TFL-2, two plasmids, in strains TFO, TFBk, and TFV-1,
      and three plasmids were detected in strain TFN-d. The adaptation of strain TFN-d
      to sulfide concentrate and the adaptation of strain TFV-1 to S0, FeS2, or sulfide
      concentrate resulted in a change in the number of plasmids occurring in cells. In
      cells of strain TFN-d adapted to sulfide concentrate, the number of plasmids
      decreased from three to two. The number of plasmids in cells of strain TFV-1
      adapted to different substrates varied from three to six depending on the energy
      source present in the medium: three plasmids were found after growth on FeS2,
      four after growth on S0, and six after growth on sulfide concentrate. The
      possible role of plasmids in the adaptation of A. ferrooxidans to new energy
      substrates and in the regulation of the intensity of their oxidation is
      discussed.

PMID- 14679905
TI  - [The transformation of the unicellular alga Chlamydomonas reinhardtii by
      electroporation].
AB  - The cell wall-lacking mutant CW-15 of the unicellular green alga Chlamydomonas
      reinhardtii was transformed by electroporation using plasmid pCTVHyg, which was
      constructed with the hygromycin phosphotransferase gene hpt as the selective
      marker and the Tn5 transposon of Escherichia coli under the control of the virus
      SV40 early gene promoter. Under optimal conditions (10(6) mid-exponential
      cells/ml; electric field strength 1 kV/cm; and pulse length 2 ms), the
      transformation yielded 10(3) HygR transformants per 10(6) recipient cells. The
      exogenous DNA integrated into the nuclear genome of Ch. reinhardtii was
      persistently inherited through more than 350 cell generations. The advantages of
      this system for the transformation of Ch. reinhardtii with heterologous genes are
      discussed.

PMID- 14679906
TI  - [The use of the [13C]/[12C] ratio for the assay of the microbial oxidation of
      hydrocarbons].
AB  - The study deals with a comparative analysis of the relative abundances of the
      carbon isotopes 12C and 13C in the metabolites and biomass of the Burkholderia
      sp. BS3702 and Pseudomonas putida BS202-p strains capable of utilizing aliphatic
      (n-hexadecane) and aromatic (naphthalene) hydrocarbons as sources of carbon and
      energy. The isotope composition of the carbon dioxide, biomass, and
      exometabolites produced during the growth of Burkholderia sp. BS3702 on n
      hexadecane (delta 13C = -44.6 +/- 0.2@1000) were characterized by the isotope
      effects delta 13CCO2 = -50.2 +/- 0.4@1000, delta 13Cbiom = -46.6 +/- 0.4@1000 and
      delta 13Cexo = -41.5 +/- 0.4@1000, respectively. The isotope composition of the
      carbon dioxide, biomass, and exometabolites produced during the growth of the
      same bacterial strain on naphthalene (delta 13C = -21 +/- 0.4@1000) were
      characterized by the isotope effects delta 13CCO2 = -24.1 +/- 0.4@1000, delta
      13Cbiom = -19.2 +/- 0.4@1000 and delta 13Cexo = -19.1 +/- 0.4@1000, respectively.
      The possibility of using the isotope composition of metabolic carbon dioxide for
      the rapid monitoring of the microbial degradation of petroleum hydrocarbons in
      the enviroment is discussed.

PMID- 14679907
TI  - [Identification of the key genes of naphthalene catabolism in soil DNA].
AB  - The key genes nahAc and xylE of the naphthalene catabolism of fluorescent
      Pseudomonas spp. in the total soil DNA samples were detected by the polymerase
      chain reaction (PCR) technique. The collection of fluorescent Pseudomonas spp.
      was screened for the occurrence of these genes. The results obtained show the
      possibility of using this approach in the goal-directed search for plasmid
      containing naphthalene-degrading fluorescent pseudomonads in soil. The
      distribution of the naphthalene catabolism genes in soils contaminated with
      creosote and petroleum products was also studied.

PMID- 14679908
TI  - [Sulfobacillus sibiricus sp. nov., a new moderately thermophilic bacterium].
AB  - In the course of pilot industrial testing of a biohydrometallurgical technology
      for processing goldarsenic concentrate obtained from the Nezhdaninskoe ore
      deposit (East Siberia, Sakha, Yakutiya), a new gram-positive rod-shaped spore
      forming moderately thermophilic bacterium (designated as strain N1) oxidizing
      Fe2+, S0, and sulfide minerals in the presence of yeast extract (0.02%) was
      isolated from a dense pulp. Physiologically, strain N1 differs from previously
      described species of the genus Sulfobacillus in having a somewhat higher optimal
      growth temperature (55 degrees C). Unlike the type strain of S.
      thermosulfidooxidans, strain N1 could grow on medium with 1 mM thiosulfate or
      sodium tetrathionate as a source of energy only within several passages and
      failed to grow, in the absence of an inorganic energy source, on media with
      sucrose, fructose, glucose, reduced glutathione, alanine, cysteine, sorbitol,
      sodium acetate, or pyruvate. The G + C content of the DNA of strain N1 was 48.2
      mol %. The strain showed 42% homology after DNA-DNA hybridization with the type
      strain of S. thermosulfidooxidans and 10% homology with the type strain of S.
      acidophilus. The isolate differed from previously studied strains of S.
      thermosulfidooxidans in the structure of its chromosomal DNA (determined by the
      method of pulsed-field gel electrophoresis) which remained stable as growth
      conditions were changed. According to the results of the 16S rRNA gene analysis,
      the new strain forms a single cluster with the bacteria of the species
      Sulfobacillus thermosulfidooxidans (sequence similarity of 97.9-98.6%). Based on
      these genetic and physiological features, strain N1 is described as a new species
      Sulfobacillus sibiricus sp. nov.

PMID- 14679909
TI  - [On the adaptive nature of the dissociation process in Bacillus thuringiensis].
AB  - The process of dissociation into variants differing in colony morphology
      occurring in batch cloned cultures of two Bacillus thuringiensis strains
      belonging to different subspecies was studied at optimal and elevated
      temperatures. An increase in the cultivation temperature to 40 degrees C resulted
      in an increase in the fraction of R variants to 100% after 72 h of cultivation of
      either of the strains. This increase was not due to the selection of forms with
      greater resistance to elevated temperature. The level of resistance to elevated
      temperature was determined by the strain genotype and did not correlate with
      morphological characteristics of the colonies.

PMID- 14679910
TI  - [Alkalitolerant yeasts from natural biotopes].
AB  - Using a solid nutrient medium containing alkaline buffer (pH 10) and an
      antibiotic, alkalitolerant yeasts were isolated from samples of soda-rich saline
      soils (solonchaks) of Armenia (Arazdayan) and the Transbaikal Region (the Kungur
      Steppe). The species diversity of the yeast populations of the tested soda-rich
      soils was relatively insignificant. They only contained alkalitolerant
      representatives of asporogenic capsulated yeasts belonging to the species
      Cryptococcus laurentii, C. albidus, Rhodotorula glutinis, R. mucilaginosa, and
      Sporobolomyces roseus. C. laurentii representatives clearly dominated the
      isolates obtained, their number exceeding that of the other species by 2-3 orders
      of magnitude. All of the isolates grew on acidic wort agar, suggesting that they
      did not include obligate alkaliphiles.

PMID- 14679911
TI  - [Distribution and physiology of microorganisms in petrochemical oily sludge of
      plant].
AB  - The occurrence, vertical distribution, and the physiological state of
      microorganisms in a petrochemical oily sludge deposit were studied. The total
      number and the number of viable microbial cells at depths of 0.2 and 3 m were
      about 10 and 10(8) cells/g dry wt. sludge. Most microbial cells taken from the
      middle (1 m deep) and the bottom (3 m deep) sludge horizons showed a delayed
      colony-forming ability, which suggested that the cells occurred in a
      hypometabolic state. The relative number of microaerobic denitrifying
      microorganisms steeply increased with depth. The amount of microorganisms
      tolerant to 3, 5, and 10% NaCl and capable of growing at 7 and 40 degrees C
      varied from 10(2) to 10(8) CFU/g dry wt. sludge. Petrochemical oily sludge was
      found to maintain the growth of heterotrophs, among which the degraders of oily
      sludge and ten different individual polycyclic aromatic hydrocarbons were
      detected. The occurrence of highly adaptable microorganisms with an adequate
      metabolic potential in the petrochemical oily sludge deposit implies that its
      bioremediation is possible without introducing special microorganisms.

PMID- 14679912
TI  - [Microbial complexes from apogeotropic roots and from rhizosphere of cycad
      plants].
AB  - The microbial complexes of soil, the rhizosphere, and the rhizoplane of the
      apogeotropic (coralloid) roots of cycad plants were comparatively studied. The
      aseptically prepared homogenates of the surface-sterilized coralloid roots did
      not contain bacterial microsymbiont, indicating that it was absent in the root
      tissues. At the same time, associated bacteria belonging to different taxonomic
      groups were detected in increasing amounts in the cycad rhizoplane, rhizosphere,
      and the surrounding soil. The bacterial communities found in the cycad rhizoplane
      and the surrounding soil were dominated by bacteria from the genus Bacillus. The
      saprotrophic bacteria and fungi colonizing the cycad rhizosphere and rhizoplane
      were dominated by microorganisms capable of degrading the plant cell walls. The
      local degradation of the cell wall was actually observed on the micrographs of
      the thin sections of cycad roots in the form of channels, through which symbiotic
      cyanobacterial filaments can penetrate into the cortical parenchyma.

PMID- 14679913
TI  - [Cyanobacterial community formed during the degradation of apogeotropic roots of
      cycads].

PMID- 14679914
TI  - [Chemotherapy and NSAIDs in neoplastic disease. Role of anti-secretory preventive
      therapy].
AB  - The patients treated by chemotherapy should be considered at high-risk for
      developing serious lesions of upper gastrointestinal tract. Several factors
      should be considered during the initial management of these patients, such as the
      presence and the staging of the malignancy, the cytotoxic effects of the
      antiblastic drugs, the co-administration of NSAIDs and corticosteroids, and the
      possible co-existence of Helicobacter pylori infection, hiatal hernia, and gastro
      esophageal reflux. In order to prevent gastro-duodenal damage, the optimal
      approach first has to include an accurate clinical and pharmacological
      evaluation. The upper gastrointestinal endoscopy should also be performed in
      neoplastic patients undergoing chemotherapy before starting treatment. Proton
      pump inhibitors can play a major role in these patients to prevent gastro
      duodenal damages, and to relieve dyspeptic symptoms.

PMID- 14679915
TI  - [Mesenchymal stem cells: from biology to clinical applications].
AB  - Mesenchymal stem cells (MSC) are multipotent cells present in a variety of
      tissues during human development and in adults mainly in bone marrow. Mesenchymal
      stem cells may be isolated and expanded in vitro and they are capable to
      differentiate into a variety of tissues, including bone, cartilage, muscle and
      adipose tissue. In this review we briefly analyze the main biological features of
      MSC with particular attention to their interaction with hemopoietic system and to
      their differentiative properties. Finally, we focus on the main MSC applications
      both in the fields of genetic and tissue engineering.

PMID- 14679916
TI  - [Cost analysis in Italy of various strategies for the treatment of Parkinson
      disease in the advanced phase].
AB  - OBJECTIVE: To perform a comparative economic evaluation of therapies--L-dopa
      drugs, subcutaneous infusion of apomorphine and surgical intervention of Deep
      Brain Stimulation (DBS)--for the treatment of advanced Parkinson's disease (APD)
      and to verify the level of assistance guaranteed in Italy to patients affected by
      APD. METHODS: Literature review and Delphi Panel to collect data about the
      efficacy of the therapies for the treatment of APD and the use of healthcare
      resources for such therapies. Field survey to investigate financing mechanisms of
      the therapeutical alternatives in the Italian regions; cost-analysis over five
      years (NHS perspective); cost-analysis (hospital perspective) for the initial
      administration of therapeutic alternatives. RESULTS: Literature review shows that
      the reduction of the "off-periods" is 62% for Apomorphine and 80-90% for DBS
      compared to traditional therapy. The 5-years economic analysis from the NHS
      perspective shows that the cost of a patients with APD is [symbol: see text]
      58.065 if treated with traditional therapy, [symbol: see text] 36.423 (including
      infusional pump and the drug) with subcutaneous apomorphine and respectively
      [symbol: see text] 56.489 and [symbol: see text] 41.379 (depending on
      reimbursement of electrodes and neurostimulator on top of the DRG tariff) with
      DBS. The field survey, highlighted that Regions which currently reimburse the
      infusion pump for apomorphine and the electrodes and neurostimulator for DBS--on
      top of the DRG tariff--are a very limited number. CONCLUSIONS: Apomorphine and
      DBS in the treatment of APD show higher efficacy and lower costs compared to
      traditional therapy.

PMID- 14679917
TI  - [Validity of the International Prognostic Index in non-Hodgkin's lymphomas of
      varying grades of malignancy].
AB  - OBJECTIVE: The "International Prognostic Index" (IPI) has been published for
      patients with histological intermediate grade malignancy non-Hodgkin's lymphoma
      (NHL) according to the Working Formulation (WF). The IPI is based on pre
      treatment clinical characteristics: age, performance status, Ann Arbor stage,
      extranodal sites, serum lactate-dehydrogenase concentration. We investigated
      whether the IPI also had prognostic value for NHL patients with a low grade
      malignancy or high grade malignancy according to the WF. PATIENTS AND METHODS:
      Our series included 192 patients with NHL, diagnosed in a single institution
      between 1986 and 1998. In each patient the relationship among IPI, response to
      therapy and survival was investigated. RESULTS: The IPI turned out to be of
      prognostic value for response rate and survival in our unselected cohort of
      patients, as well. In each of the three WF classes separately (low, intermediate,
      high grade malignancy), the four IPI classes showed going from low to high risk
      substantially decreasing response rates and survival percentages. CONCLUSIONS:
      The IPI is confirmed as an important tool for prognostic evaluation of NHL
      patients: an integration of IPI, histological grading and serum beta 2
      microglobulin concentration is supported.

PMID- 14679918
TI  - [Fenoldopam and kidney function in a case of abdominal aortic pseudoaneurysm with
      supra-renal clamping in an emergency protocol].
AB  - The renal haematic flow decrease, the vasoconstriction and the local vascular
      resistance increase, associated with descending aortic cross-clamping, before the
      origin of renal arteries, can be contrasted by continuous infusion of fenoldopam,
      a dopamine analog with selective action on DA1-receptors. The renal effects of
      this molecule are renal plasmatic flow increase and local vascular resistance
      decrease, without important haemodynamic changes, with mild cardiovascular
      modification, even at high doses, in hypertensive and non hypertensive patients,
      also in normal volume condition and hypovolemic condition. This selective action
      at renal level allows the use of fenoldopam also in surgical emergencies, in
      patients with low cardiovascular function. The case report here presented
      demonstrated a beneficial renal effects of continuous infusion of fenoldopam and
      its easy to use, in emergency situations. These findings could be extrapolated
      for other patients or suggested for additional research.

PMID- 14679919
TI  - [Problems in the management of HIV infection in clinical practice. Patients still
      on dual therapy 8 years after the introduction of HAART].
AB  - Eight years after the introduction of HAART as the standard therapy of HIV
      disease, around one fifth of treated patients of our cohort still rely on
      isolated dual nucleoside analogue administration, mostly due to an apparently
      effective treatment initiated with these last drugs before the HAART era, or
      severe intolerance to triple regimens based on protease inhibitors or non
      nucleoside reverse transcriptase inhibitors, or patient's refusal of HAART. Three
      representative case reports are described, and their implications discussed on
      the ground of current guidelines of antiretroviral therapy and common clinical
      practice.

PMID- 14679920
TI  - [Rational use of the glycemic stick in hospitals].
AB  - For best management of the diabetic patient and the cost-benefit relationship of
      bedside blood glucose monitoring use in hospital, we suggest an acting algorithm
      based on literature directions and on the clinical experience of an Internal
      Medicine Department.

PMID- 14679921
TI  - [Antileukotrienes in the therapy of bronchial asthma].
AB  - Cysteinyl-leukotrienes (Cys-LTs) are mediators released in bronchial asthma and
      are both direct bronchoconstriction and proinflammatory substances that mediated
      several steps in the pathophysiology of chronic asthma, including inflammatory
      cells recruitment, vascular leakage, and possibly airway remodelling. Available
      evidence from clinical trials and real-word experience derived from managing
      patients with asthma justifies a broader role for antileukotriene drugs (anti
      LTs) in asthma management than that recommended in the National Asthma Education
      and Prevention Program and National Institute of Health treatment guidelines.
      Anti-LTs seem to be effective alternatives to inhaled corticosteroids (ICS)
      either as monotherapy or as adjunctive therapy that reduces the need for higher
      doses of ICS in patients with mild-to-moderate persistent asthma. This class of
      drugs may be used as adjunctive therapy for all levels of disease severity
      because they are effective in combination with ICS during long-term maintenance
      therapy. The anti-LTs seem especially effective in preventing aspirin-induced
      asthma providing an additional advantage of reducing nasal congestion in patients
      with both asthma and rhinitis and in the treatment of exercise induced-asthma.
      This class of drugs have several features that are likely to promote adherence to
      treatment and are generally well tolerated. The available clinical data suggest
      that anti-LTs should be considered as a therapeutic option or as additive therapy
      in patients with mild to severe asthma.

PMID- 14679922
TI  - [Fungal infections in transplantation patients].
AB  - Invasive fungal infections have became one of the principal obstacles to
      successful solid organ and bone marrow transplantation. The natural history and
      incidence of systemic fungal infection varies with the type of organ transplanted
      and the immunosuppressive therapy administered; the majority of infections occur
      within the first two months after transplantation. The most common fungi that
      cause disease in transplant recipients are Candida spp. and Aspergillus spp. The
      clinical presentations of fungal infections in solid-organ transplant recipients
      are non specific and often overlap with other infectious and non infectious
      processes; for this reason it's important maintain a high index of suspicion for
      this type of infection so to start an aggressive diagnostic and therapeutic
      approach. Difficulty in establishing an etiological diagnosis, lack of effective
      therapy in certain situations, difficult management of certain antifungal drugs
      due to toxicity and/or interaction with immunosuppressive drugs, and limited data
      on effective antifungal prophylactic regimens in solid-organ transplantation
      represent major problems in the treatment of fungal infection in this population.

PMID- 14679923
TI  - Failure of combination abacavir + tenofovir + lamivudine (3TC).
AB  - An antiretroviral combination worked much less well than expected in controlling
      HIV. Patients using all three of these drugs together should talk with their
      doctor and consider changing treatment.

PMID- 14679924
TI  - FTC (Emtriva) approved.
AB  - A new antiretroviral was approved July 2--the 19th now approved in the U.S. It is
      chemically related to 3TC.

PMID- 14679925
TI  - New HIV treatment guidelines give more advice.
AB  - New U.S. treatment guidelines give doctors and patients more guidance--especially
      on what antiretrovirals to start with. Advice on when to start has not changed.
      While the new guidelines are more useful than previous editions, it remains
      critically important to have a physician with extensive experience in treating
      HIV.

PMID- 14679926
TI  - Colon polyps. Little bumps, big significance.

PMID- 14679927
TI  - Health tips. Flying with a cold.

PMID- 14679928
TI  - Diabetes drug may also benefit blood vessels.

PMID- 14679930
TI  - Alcohol and health. The pros and cons.

PMID- 14679929
TI  - Researchers ponder a link between folate and depression.

PMID- 14679931
TI  - Vitamin K. A possible help in bone health.

PMID- 14679932
TI  - Endometrial ablation. Stop the bleeding.

PMID- 14679933
TI  - Can you tell me if there's any health advantage to using extra-virgin olive oil
      instead of virgin olive oil or just plan old olive oil?

PMID- 14679934
TI  - I've had problems with excess facial hair for years. I've heard that doctors can
      remove unwanted hair with lasers. Is this safe?

PMID- 14679935
TI  - The power of brotherly love.

PMID- 14679936
TI  - To break or not to break, that is still the question.

PMID- 14679937
TI  - New formulations, new drugs...not always better.

PMID- 14679938
TI  - We want our Trizivir!

PMID- 14679939
TI  - And they said this was a gay, white male disease.

PMID- 14679940
TI  - Positive women speak out about HIV and pregnancy.

PMID- 14679942
TI  - "The happiest day of our life". A gay couple living with HIV adopts.

PMID- 14679943
TI  - Having children when he's positive and she's negative.

PMID- 14679941
TI  - Full circle--one woman's story.

PMID- 14679944
TI  - Step-by-step: sperm washing.

PMID- 14679945
TI  - Perinatal HIV transmission and birth options for HIV positive mothers.

PMID- 14679946
TI  - Viread, Epivir and Ziagen combination: failure in naive patients with a once
      daily regimen.

PMID- 14679947
TI  - Blood pressure drugs. What are the options?

PMID- 14679948
TI  - Insulin therapy for type 2 diabetes.

PMID- 14679949
TI  - Diabetes Resources. Back to school.

PMID- 14679950
TI  - Navigating mental health care.

PMID- 14679951
TI  - Pizza pizzazz.

PMID- 14679952
TI  - Using meal replacements for weight loss.

PMID- 14679953
TI  - Selecting an insulin program for type 1 diabetes.

PMID- 14679955
TI  - Diabetes quiz. How much do you know about reading food labels?

PMID- 14679954
TI  - New horizons in diabetes treatment.

PMID- 14679956
TI  - Supermarket smarts. Dips, spreads, and salsas.

PMID- 14679957
TI  - Sports and fitness. The high price of inactivity.

PMID- 14679958
TI  - Diabetes basics. What is diabetes?

PMID- 14679960
TI  - A study of cohesive patterns and dynamic choices utilized by two schizophrenic
      patients in dialog, pre- and post medication.

PMID- 14679959
TI  - For parents. Overcoming a fear of needles.

PMID- 14679961
TI  - Assessing your health risks. When warned by the media about a health risk,
      determine how it applies to you.

PMID- 14679962
TI  - Breast-cancer drug letrozole picks up where tamoxifen leaves off. But we don't
      know who stands to benefit the most from this follow-up approach.

PMID- 14679963
TI  - Dye enhancement for digital mammograms.

PMID- 14679965
TI  - Diabetes on the rise. The one-third of Americans born in 2000 who are projected
      to develop diabetes will face a high risk of stroke, kidney disease, vision loss,
      and several other complications.

PMID- 14679964
TI  - Lifestyle advice for cancer survivors.

PMID- 14679966
TI  - Bypass surgery in the elderly is feasible. Heart bypass surgery can benefit
      people in their mid-70s and beyond, though recovery may take longer than in
      younger people.

PMID- 14679967
TI  - Exercise tests may predict heart disease risk in women.

PMID- 14679968
TI  - Nighttime's the right time for some statin drugs.

PMID- 14679969
TI  - Snow shoveling spurs sudden heart-related death.

PMID- 14679971
TI  - Early detection of rheumatoid arthritis made easier. Accurate early diagnosis may
      facilitate treatment decisions.

PMID- 14679972
TI  - Questions & answers. How might my doctor confirm his suspicion that I have
      gallbladder disease?

PMID- 14679970
TI  - Injectable drug dampens bone loss.

PMID- 14679973
TI  - Questions & answers. What's the difference between gout and pseudogout?

PMID- 14679974
TI  - Malaria can hide after travel.

PMID- 14679975
TI  - New Alzheimer's drug approved.

PMID- 14679976
TI  - Health website for older adults launched.

PMID- 14679977
TI  - [A clinical study of the treatment of 83 patients dentine hypersensitivity with
      Green Or].

PMID- 14679978
TI  - [Fibrinolytic syndrome during surgery for benign prostatic hypertrophy (50 cases
      in the urology service at the Aristide le Dantec University Hospital Center)].
AB  - Prostate's surgery is an haemorrhagic one owing to difficulties of surgical
      haemostasis and anomalies of the blood coagulation. The aim of this study to
      assess haemostasis anomalies after protatectomy for benign prostatic hyperplasia
      (BPH). We have performed a prospective study including 50 men of more of 55 years
      old. All of them underwent suprapubic open prostatectomy. Significant pertubation
      of haemostasis, particularly fibrinolysis has been found. We have noticed fibrin
      degradation product in 88% of cases after intervention versus 62% before (p <
      0.001) and a decrease of plasminogen rate in 94.4% of operated patients versus
      82% before. The older the patient were, more important were the pertubations.
      Moreover, the anomalies were most important when the duration of surgery lasted
      more than one hour and when the BPH was voluminous. However, the disturbance of
      haemostasis was rarely associated to clinical symptoms. So, we do not recommend
      any therapeutic when clinical symptoms are absent. Biological screening the day
      of surgery, the day after and one week later are necessary to prevent
      haemorrhage.

PMID- 14679979
TI  - [Antiphospholipid antibodies and recurrent spontaneous abortions at the Aristide
      Le Dantec University Hospital Center].
AB  - Antiphospholipids including lupus anticoagulants (LA) and anticardiolipins (ACL)
      are known to be able to lead to many obstetricals complications like gravidic
      chorea, eclampsia and repeated spontaneous abortion. Our objective was to
      determine place of antiphospholipids among women presenting repeated spontaneous
      abortion in Senegal. We tested prospectively 96 women in a breeding age with a
      past history of at least 2 spontaneous abortion. 14.6% and 21.1% of tese women
      present present respectively LA and ACL. The prevalence of antiphospholipids in
      among women presenting repeated abortion is higher in Senegal and similar to
      those previously reported confirming its place in this pathology important. A
      strategy of diagnosis should be defined between obstetricians and biologists in
      order to improve the obstetrical prognosis.

PMID- 14679980
TI  - [Toxocological study of Guiera senegalensis Lam (Combretaceae)].
AB  - The study was based on an aqueous extract derived from a 60 degrees ethanolic
      tincture containing 0.032 g of dry matter per ml. The leaves of Guiera
      senegalensis Lam (Combretaceae) were collected in December 1991 at Nguekhokh a
      village within 20 km from Mbour (Senegal). The extract was administered for six
      months through daily forced-feeling at 2 g/kg to Wistar male and female rats
      whose weight at the beginning of the experiment tanged between 140 g and 180 g.
      The urine was analysed during the study and the animals were weighed every four
      weeks. At the end of the experiment, the animals were slaughtered and various
      analyses carried out. Haematological features in relation with erythropoiesis,
      haemoglobinogenesis and leucopoiesis, were studied in relation with renal and
      hepatic functions; biochemical features too. Some organs (heart, lungs, kidneys,
      brain, cerebellum, spleen and liver) were removed and examined in order to detect
      possible lesions following the experiment. Judging by the results, Guiera
      senegalensis Lam (Combretaceae), as used in the experiment, did not show any
      significant toxicity.

PMID- 14679981
TI  - [Bilateral swelling of the parotid glands as part of a systemic disease].
AB  - In four patients, a man aged 34 years and three women aged 35, 32 and 55 years
      respectively bilateral swelling of the parotid glands was caused by systemic
      disease i.e. HIV-salivary gland disease, mucosa-associated lymphoid-tissue (MALT)
      lymphoma, sarcoidosis with coexisting Sjogren's syndrome, and sialosis and
      hypothyroidism, respectively. The HIV patient was treated with antiretroviral
      therapy, the first two women were treated expectantly and the third woman was
      given a thyroid hormone supplement which resulted in regression of the bilateral
      parotid enlargement. Bilateral enlargement of the parotid glands is not
      necessarily caused by infection, it can also be of systemic origin. Minimal
      invasive investigations of the salivary glands, such as sialography, measurement
      of salivary secretion rate (sialometry) and analysis of salivary composition
      (sialochemistry) can offer valuable information about the origin of the parotid
      gland swelling. Histopathological investigation of an incision biopsy of the
      parotid gland is an easy way to confirm the diagnosis. The morbidity associated
      with parotid biopsy is negligible.

PMID- 14679982
TI  - [Physician shortage at the regional level in the United Kingdom].
AB  - The National Health Service in the United Kingdom is experiencing a serious
      shortage of healthcare staff in several specialties; as a result, significant
      difficulties affecting both the ability to deliver the service and the quality,
      have been documented. Considering the specific features of the healthcare
      workforce, a holistic approach to the shortage has been suggested. This approach
      entails various long-term policy interventions, focusing on the improvement of
      recruitment and retention, changes in the skill mix of healthcare personnel,
      improvement of pay and working conditions, expanding training places and enhanced
      workforce planning. This strategy is underpinned by the premise that the causes
      of the shortages, the discontent amongst healthcare personnel and the poor
      quality of care that results, are all interrelated. This article deals
      specifically with shortage of medical doctors in the 4 components of the Kingdom.
      Each of them manages autonomously their health service and is designing separate
      plans to overcome medical staff shortage. However, these plans are similar and
      the same outcomes are expected in the 4 regions.

PMID- 14679983
TI  - [Management of cystic fibrosis].

PMID- 14679984
TI  - [Management of patients (children and adults) with cystic fibrosis].

PMID- 14679985
TI  - Acetylcholinesterase activity in grass shrimp and aqueous pesticide levels from
      South Florida drainage canals.
AB  - Freshwater drainage canals in South Florida are utilized to manage water in
      agricultural, urban, and water conservation areas and, as a result, collect urban
      and agricultural storm runoff that is discharged into the Atlantic Ocean and Gulf
      of Mexico. Pesticides in this runoff may be toxic to the biota inhabiting these
      waters. This study evaluated the effects of contaminants in South Florida canals
      draining into Biscayne Bay on the estuarine grass shrimp (Palaemonetes
      intermedius), a representative invertebrate species. Results of surface water
      analysis for pesticides indicated that eight pesticides out of 52 analyzed were
      detected. The herbicide metolachlor was found at all nine sites in the five
      canals sampled at concentrations up to 119 ng/L. Atrazine was detected at seven
      sites at concentrations up to 29 ng/L. Three organophosphate insecticides
      (chlorpyrifos, malathion, diazinon) were detected at three sites in two canals
      (Military and North). Grass shrimp from these three sites showed significantly
      reduced levels of the acetylcholinesterase enzyme as compared to control shrimp.
      These two canals are similar in the land use areas drained--urban and suburban
      and agriculture. The results suggest that monitoring organisms for AChE levels
      can be a means of detecting exposure to organophosphorus pesticide contamination.

PMID- 14679986
TI  - Free-space ballistic laser propagation of a pulse coded data stream through fog.
AB  - We describe the use of space and polarization gates in a study of free-space
      optical communication of a coded pulse train as it passes through turbid media.
      The propagation of coded signals at 10 GHz through adverse environmental
      conditions is demonstrated. Polarization and space-gating techniques are used to
      improve the signal-to-noise ratio and to enhance the information fidelity of high
      bit-rate transmitted signals, which shows potential improvement for cloud, fog,
      and smog applications.

PMID- 14679987
TI  - Information from your family doctor. Mourner's rights.

PMID- 14679988
TI  - Re: Binocular ocular sighting dominance discovered to be gaze dependent! in
      "Further followup (Part III): A case of acute loss of binocular vision and
      stereoscopic depth perception". P.E. Romano Binocul Vis Strabismus Q 2003; 18:174
      175.

PMID- 14679990
TI  - Spine Patient Outcome Research Trial (SPORT): multi-center randomized clinical
      trial of surgical and non-surgical approaches to the treatment of low back pain.

PMID- 14679992
TI  - Alternative technologies.

PMID- 14679991
TI  - The Cat Group. Policy statement. Testing for feline immunodeficiency virus (FIV).

PMID- 14679993
TI  - Pressure sore induced by epidural catheter in a patient recieving postoperative
      pain control.

PMID- 14679994
TI  - Don't make an easy block more difficult!

PMID- 14679995
TI  - Paraverbal approach to the brachial plexus.

PMID- 14679996
TI  - Paravertebral approach to the brachial plexus: an anatomic improvement in
      technique--is it really advantageous to come from behind?

PMID- 14679998
TI  - Sheldon C. Reed, Ph.D. (November 7, 1910-February 1, 2003): genetic counseling,
      behavioral genetics.

PMID- 14679997
TI  - The use of concomitant antiplatelet drugs during neuraxial anethesia is
      contraindicated in Germany.

PMID- 14679999
TI  - Sympathetic blocks and disease progression modifying pain mechanisms.

PMID- 14680000
TI  - Identity, killing, and the boundaries of our existence.

PMID- 14680001
TI  - Ethical issues surrounding human participants research using the Internet.
AB  - The Internet appears to offer psychologists doing research unrestricted access to
      infinite amounts and types of data. However, the ethical issues surrounding the
      use of data and data collection methods are challenging research review boards at
      many institutions. This article illuminates some of the obstacles facing
      researchers who wish to take advantage of the Internet's flexibility. The
      applications of the APA ethical codes for conducting research on human
      participants on the Internet are reviewed. The principle of beneficence, as well
      as privacy and confidentiality, informed consent, deception, and avoiding harm
      are all illustrated through the use of a hypothetical online study.

PMID- 14680002
TI  - Protection of children's rights to self-determination in research.
AB  - Federal guidelines require that informed consent be obtained from participants
      when they are enrolled in a research study. When conducting research with
      children, the guidelines utilize the term permission to describe parents'
      agreement to enroll their children in a study. The basic components of consent
      and permission are well described and identical, with the exception of the person
      for whom the decision to participate is being made (i.e., oneself as opposed to
      one's child). Beyond permission, when enrolling minor participants in research,
      affirmative agreement to participate in research or assent must be obtained from
      the child participants themselves. The concept of children's assent to research,
      however, is poorly defined, resulting in inconsistency in its pursuit and
      consequently, in its utility. The interface between cognitive development,
      emotional, and social development must be examined as its pertains to this
      special situation of decision making. For this process to meaningfully protect
      minors, the assent process must be clarified, decisions regarding parental veto
      power must be more convincingly justified, and researchers must be better
      educated and held accountable for the valid execution of this process. Strategies
      for implementing the assent process more effectively are presented.

PMID- 14680003
TI  - ["Trabeculectomy and phacoemulsification. One site vs. two site approach. A
      comparative study" comment by Fernandez Escamez CS. Author reply].

PMID- 14680004
TI  - Regulation of cyclic adenosine 3',5'- monophosphate signaling and pulsatile
      neurosecretion by Gi-coupled plasma membrane estrogen receptors in immortalized
      gonadotrophin-releasing hormone neurons.
AB  - Immortalized GnRH neurons (GT1-7) express receptors for estrogen [estrogen
      receptor-alpha and-13(ERa and ERI3)] and progesterone (progesterone receptor A)
      and exhibit positive immunostaining for both intracellular and plasma membrane
      ERs. Exposure of GT1-7 cells to picomolar estradiol concentrations for 5-60 min
      caused rapid, sustained,and dose-dependent inhibition of cAMP production. In
      contrast, treatment with nanomolar estradiol concentrations for 60 min increased
      cAMP production. The inhibitory and stimulatory actions of estradiol on cAMP
      formation were abolished by the ER antagonist, ICI 182,780. The estradiol-induced
      inhibition of cAMP production was prevented by treatment with pertussis toxin,
      consistent with coupling of the plasma membrane ER to an inhibitory G protein.
      Coimmunoprecipitation studies demonstrated an estradiol-regulated stimulatory
      interaction between ERa and G,3 that was prevented by the ER antagonist, ICI
      182,780. Exposure of perifused GT1-7 cells and hypothalamic neurons to picomolar
      estradiol levels increased the GnRH peak interval, shortened peak duration, and
      increased peak amplitude. These findings indicate that occupancy of the plasma
      membrane-associated ERs expressed in GT1-7 neurons by physio-logical estradiol
      levels causes activation of a G, protein and modulates cAMP signaling and
      neuropeptide secretion.

PMID- 14680005
TI  - From diagnostic imaging... When the cervical end plate is not where it seems.

PMID- 14680006
TI  - Issues of ethics and identity in diagnosis of late life depression.
AB  - Depression is often diagnosed in patients nearing the end of their lives and
      medication or psychotherapy is prescribed. In many cases this is appropriate.
      However, it is widely agreed that a health care professional should treat sick
      persons so as to improve their condition as they define improvement. This raises
      questions about the contexts in which treatment of depression in late life is
      appropriate. This article reviews a problematic case concerning the
      appropriateness of treatment in light of the literature in bioethics. Specific
      attention is paid to the concept of authenticity and the role of suffering.
      Suffering is often the result of a situation in which one's self is damaged. In
      some circumstances, this suffering should not be seen as a symptom of illness,
      but as a reflection, in a difficult life context, of the individual's authentic
      nature. Assessment of depression in the elderly must go beyond a symptom list and
      must consider both the context of the individual's situation and his or her
      authentic self. When the symptoms reflect the individual's assessment of the
      situation in the context of the authentic self, they may be "appropriate."
      However, even when the symptoms are appropriate, if they interfere with life
      assessment and adjustment, treatment should be considered.

PMID- 14680007
TI  - From clinical imaging... When one should look at all sides of the spine.

PMID- 14680008
TI  - Divergent ethical perspectives on the duty-to-warn principle with HIV patients.
AB  - This article presents the case of an HIV-positive client who reported having
      sexual relations with an unknowing partner. The issue raised is whether the
      therapist was required to warn the unknowing partner, similar to the Tarasoff
      mandate that is imposed on therapists. The case is analyzed from an ethical
      framework similar to that presented by Beauchamp and Childress (1994). Two
      opinions are presented, each leading to different conclusions about whether the
      therapist should inform the unknowing partner. It is concluded that although such
      analysis is valuable in aiding the therapist in his or her decision-making
      process, no clear professional standard for the management of the problem is
      evident.

PMID- 14680009
TI  - Influences upon willingness to participate in schizophrenia research: an analysis
      of narrative data from 63 people with schizophrenia.
AB  - Schizophrenia affects more than 1% of the world's population, causing great
      personal suffering and socioeconomic burden. These costs associated with
      schizophrenia necessitate inquiry into the causes and treatment of the illness
      but generate ethical challenges related to the specific nature and deficits of
      the illness itself. In this article, we present a systematic analysis of
      narrative data from 63 people living with the illness of schizophrenia collected
      through semistructured interviews about their attitudes, beliefs, and experiences
      related to psychiatric research. In the comments of these individuals, half of
      whom had had prior personal experience in research protocols, we identified
      factors influencing openness toward research involvement as well as deterrents
      that appear to lessen interest in participation. Clear response pattern
      differences emerged between those with prior research experience and those
      without such experience. In the discussion, we explore the key findings and
      outline the implications for safeguards in mental illness research.

PMID- 14680010
TI  - Speak-Easy: setting up a speakers bureau.

PMID- 14680011
TI  - Weight-loss drug fattens heart risks.

PMID- 14680012
TI  - Pain reliever gets buff.

PMID- 14680013
TI  - Does ACL reconstruction restore normal tibial rotation?

PMID- 14680014
TI  - Human rights watch report documents brutal conditions for mentally ill prisoners.

PMID- 14680015
TI  - Can the national addiction treatment infrastructure support the public's demand
      for quality care?

PMID- 14680016
TI  - Smile analysis.

PMID- 14680017
TI  - Premolar extraction and smile esthetics.

PMID- 14680018
TI  - Dysfunctional appliances.

PMID- 14680019
TI  - Professionalism in pharmacy. Seeking the science angle in APhA policies.

PMID- 14680020
TI  - Professionalism in pharmacy. Student-pharmacists' policies target
      professionalism.

PMID- 14680021
TI  - Synthesis of 3'-deoxy-3'-[4-(pyrimidin-1-yl)methyl-1,2,3-triazol-1-yl]thymidine
      via 1,3-dipolar cycloaddition.
AB  - The synthesis of new 3'-deoxy-3'-[4-(pyrimidin-1-yl)methyl-1,2,3-triazol-1-yl]
      thymidine 6a-f, from 3'-azido-3'-deoxy-5'-O-monomethoxytrityl-thymidine is
      described. The key step is the 1,3-dipolar cycloaddition between the azido group
      of the protected AZT 3 and N-1-propargylpyrimidine derivatives 2a-f. All new
      derivatives 6a-f were evaluated for their inhibitory effects against the
      replication of HIV-1 (IIIB), HIV-2 (ROD). No marked activity was found.

PMID- 14680022
TI  - 5'-nor carbocyclic ribavirin.
AB  - An efficient synthesis of 5'-nor carbocyclic ribavirin (4) is described in 13
      steps from conveniently available (+)-(IR,4S)-4-hydroxy-2-cyclopenten-1-yl
      acetate (6). Compound 4 was evaluated against the following viruses: herpes
      simplex type 1 and 2, vaccinia, cowpox, smallpox, Ebola, hepatitis B, hepatitis
      C, adenovirus type 1, influenza A (H1N1 and H3N2), influenza B, parainfluenza
      type 3, Pichinde, Punta Toro A, respiratory syncytial, rhinovirus type 2,
      Venezuelan equine encephalitis, yellow fever, and West Nile. No activity was
      found nor was there any cytotoxicity to the viral host cells.

PMID- 14680023
TI  - Novel chiral phosphoramidite monomers from (R)- and (S)-1,3-butanediol: synthesis
      of modified oligonucleotides and binding affinity studies.
AB  - Two optically active phosphoramidite monomers for modified
      oligodeoxyribonucleotides were prepared. These monomers were then introduced into
      dodecanucleotides in the middle of the sequences. The modified dodecanucleotides
      were characterized by various analytical methods including MALDI-TOF mass
      spectrometry and Tm values were obtained to appraise the binding affinity, by
      measuring change in UV absorbance at 260 nm.

PMID- 14680024
TI  - Synthesis and biological evaluation of some 5-nitro- and 5-amino derivatives of
      2'-deoxycytidine, 2',3'-dideoxyuridine, and 2',3'-dideoxycytidine.
AB  - In this article, we describe the synthesis of 5-nitro-1-(2-deoxy-alpha-D-erythro
      pentofuranosyl)cytosine (4alpha), 5-nitro-1-(2-deoxy-beta-D-erythro
      pentofuranosyl)cytosine (4beta), 5-amino-1-(2-deoxy-alpha-D-erythro
      pentofuranosyl)cytosine (5alpha), 5-nitro-1-(2-deoxy-beta-D-erythro
      pentofuranosyl)cytosine (5beta), 5-nitro-1-(2,3-dideoxy-beta-D
      ribofuranosyl)uracil (6beta), 5-amino-1-(2,3-dideoxy-alpha,beta-D
      ribofuranosyl)uracil (7), 5-nitro-1-(2,3-dideoxy-alpha,beta-D
      ribofuranosyl)cytosine (8) and 5-amino-1-(2,3-dideoxy-beta-D
      ribofuranosyl)cytosine (9beta). The prepared compounds were tested for their
      activity against HIV and HBV viruses, but they did not show significant activity.

PMID- 14680025
TI  - Synthesis and anti-HBV activity of thiouracils linked via S and N-1 to the 5
      position of methyl beta-D-ribofuranoside.
AB  - Reverse nucleoside derivatives of 2-(methylsulfanyl)uracils 6a-d were prepared by
      treating of the sodium salt of 2-(methylsulfanyl)uracils (5a-d) with methyl 2,3-O
      isopropylidene-5-O-p-toluenesulfonyl-beta-D-ribofuranoside (2). The alkylation of
      2-thiouracils 4a-d with methyl 5-deoxy-5-iodo-2,3-O-isopropylidene-D
      ribofuranoside (3) afforded the corresponding S-ribofuranoside derivatives 8a-d.
      Deisopropylidenation of 6a-d and 8a-d afforded the corresponding deprotected
      derivatives 7a-d and 9a-d, respectively. The Anti-HBV activity of selected
      compounds was studied.

PMID- 14680026
TI  - Synthesis of 2-(3'-azido- and 3'-amino-3'-deoxy-beta-D-ribofuranosyl)thiazole-4
      carboxamide.
AB  - In view of biological activities of tiazofurin and azido or aminosugar
      nucleosides, novel azido- and amino-substituted tiazofurin derivatives (1 and 2)
      were efficiently synthesized starting from 1,2;5,6-di-O-isopropylidene-D-glucose.

PMID- 14680027
TI  - Synthesis, anti-HIV, and cytotoxic activity of new AZT conjugates of steroid
      acids.
AB  - In an attempt to discover potent anti-HIV agents devoid of the serious toxicity
      of the current HIV-reverse transcriptase inhibitors, three steroid prodrugs of
      AZT have been synthesized and their anti-HIV profiles determined with CEM-SS cell
      line. Two of the prodrugs were active against HIV, though weaker than AZT. The
      third agent was totally inactive against HIV. However, it demonstrated remarkably
      high anti-growth activities. Further experiments established that growth
      inhibition of the third agent was caused by induction of apoptosis rather than
      general necrosis.

PMID- 14680028
TI  - A new approach to the synthesis of benzothiazole, benzoxazole, and pyridine
      nucleosides as potential antitumor agents.
AB  - A modified nitrogen and sulfur glycosylation reaction involving benzothiazole
      benzoxazole and pyridine nucleoside bases with furanose and pyranose sugars are
      described. Conformational analysis has been studied by homo- and heteronuclear
      two-dimensional NMR methods (2D DFQ-COSY, HMQC and HMBC). The N and S sites of
      glycosylation were determined from the 1H, 13C heteronuclear multiple-quantum
      coherence (HMQC) experiments. All the deprotected nucleosides were tested for
      their potential antitumor activity.

PMID- 14680029
TI  - Creating a balanced scorecard for a hospital system.
AB  - In 1999, hospitals in Ontario, Canada, collaborated with a university-based
      research team to develop a report on the relative performance of individual
      hospitals in Canada's most populated province. The researchers used the balanced
      scorecard framework advocated by Kaplan and Norton. Indicators of performance
      were developed in four areas: clinical utilization and outcomes, patient
      satisfaction, system integration and change, and financial performance and
      condition. The process of selecting, calculating, and validating meaningful
      indicators of financial performance and condition is outlined. Lessons learned
      along the way are provided. These lessons may prove valuable to other finance
      researchers and practitioners who are engaged in performance measurement
      endeavors.

PMID- 14680030
TI  - No mission<-->no margin: it's that simple.
AB  - The authors describe their experience in developing a strategy-focused
      organization using the balanced scorecard methodology. They achieved this at Duke
      Children's Hospital by aligning the clinicians and administrators around a single
      integrated platform that linked improving business processes with achieving
      quality clinical outcomes. By organizing in this manner, they reduced cost by
      dollars 30 million and increased net margin by dollars 15 million while improving
      outcomes and staff satisfaction. This article describes a methodology to achieve
      strategic control of the organization, increase the knowledge of key
      stakeholders, and transform the organization to optimize the organization's
      performance.

PMID- 14680031
TI  - Financial dashboard reporting for the hospital industry.
AB  - Most senior executives and board members experience information overload in their
      decision making roles. They simply receive an excessive amount of unrelated data
      that is not benchmarked to standards that enable them to make effective
      decisions. This is an unfortunate situation given the information technology and
      the availability of public data that exists today. Many firms in a variety of
      industry sectors have combined the concept of "balanced scorecards" with
      "dashboard" reporting to revamp their senior level executive reporting systems. A
      sample dashboard reporting system for a hospital is outlined in this paper.

PMID- 14680032
TI  - Developing an activity-based management system for the Army Medical Department.

PMID- 14680033
TI  - Using an integrated measurement system as a common language: lessons from the
      U.S. Army medical department.
AB  - The Process of developing an integrated measurement system for the U.S. Army
      Medical Department (AMEDD) is examined in this study. A fundamental issue is
      whether the measures of performance accumulated by any information system are the
      correct ones and whether these measures appropriately reflect managers' decision
      making. Measurement is proposed as a solution to performance barriers. The four
      steps involved in building the AMEDD integrated measurement system (IMS) model
      are set out. Strategy is explored as the key input to the IMS model. An activity
      based management (ABM) model that can support the required IMS cost-based
      measures is also described and the interrelationship between the two models is
      illustrated. The key test for application of the IMS model will be whether
      linking strategy and measurement results in information that improves decision
      making.

PMID- 14680034
TI  - Understanding medical group financial and operational performance: the
      synergistic effect of linking statistical process control and profit and loss.
AB  - There is ongoing pressure for medical groups owned by not-for-profit health care
      systems or for-profit entrepreneurs to generate profit. The fading promise of
      superior strategy through health care integration has boards of directors
      clamoring for bottom-line performance. While prudent, sole focus on the bottom
      line through the lens of the profit-and-loss (P&L) statement provides incomplete
      information upon which to base executive decisions. The purpose of this paper is
      to suggest that placing statistical process control (SPC) charts in tandem with
      the P&L statement provides a more complete picture of medical group performance
      thereby optimizing decision making as executives deal with the whitewater issues
      surrounding physician practice ownership.

PMID- 14680035
TI  - The Results Act: a challenging management framework.
AB  - This article provides the reader with a basic understanding of the Government
      Performance and Results Act of 1993. The Act requires federal agencies to
      institute a planning and reporting management framework to achieve results. It
      also identifies challenges federal agencies face in implementing a stronger
      results management approach and promising practices agencies can use in crafting
      their management approach.

PMID- 14680036
TI  - Lung burdens of depleted uranium in Gulf War veterans.

PMID- 14680038
TI  - Genome projects and gene therapy: gateways to next generation biological weapons.
AB  - Genomic and gene therapy research promise important gains into the treatment of
      human, animal, and plant diseases. However, there is a military aspect to this
      research that must be recognized. This research enables a new form of biological
      warfare named genomic warfare. This is the first peer-reviewed scientific article
      to discuss this threat in-depth. This article advocates that we begin to deal
      with this threat. Despite that the United States and many signatories of previous
      bioweapons treaties have agreed not to use biological weapons, mankind has a
      track record of using all of the weapons at its disposal. This article has a
      review of the literature and a basic overview of genomic research and gene
      therapy, which is followed by a discussion of how this therapy can be weaponized.
      How genomic warfare weapons might be deployed, how deployment may be detected,
      and the policies and research that would reduce this threat will be described. It
      is the aim of this article to clearly articulate that this risk exists and to
      encourage public health, scientific, political, and military leaders to take
      action to deal with the risk.

PMID- 14680037
TI  - "In the interest of humanity and the cause of science": the yellow fever
      volunteers.
AB  - The scientific discoveries of the U.S. Army Yellow Fever Board of 1900 are well
      known as are the Army physicians who led the board. Walter Reed, of course, is
      the best known, but James Carroll, Aristides Agramonte, and Jesse Lazear are also
      known, if not nationally, to their local communities. This article deals not with
      the known but with the unknown, meaning the volunteers who subjected themselves
      to the ravages of yellow fever and the real possibility of death. The year 1900
      was known as a "yellow fever year" among the locals in Cuba because in the
      preceding year the epidemics had been relatively mild. Beginning its work in June
      1900 in the midst of a deadly epidemic, the board conducted a truly remarkable
      set of experiments that set a benchmark for controlled clinical trials and
      informed consent. Because no animal model was known to be susceptible to yellow
      fever, they used human volunteers for their experiments. These volunteers were
      recruited from among Spanish immigrants and were accepted from soldiers and two
      civilians who volunteered. Over 30 men participated in the experiments, and 22
      developed yellow fever. With expected death rates of 20% to 40%, it is incredible
      that none of these volunteers died. In 1929, the U.S. government honored the
      Americans who volunteered by placing their names on a Roll of Honor published
      annually in the Army Register. The successes of the 1900 U.S. Army Yellow Fever
      Board were truly remarkable, and many of the successes were made possible by the
      men who volunteered, some repeatedly, to risk their lives "in the interest of
      humanity and the cause of science."

PMID- 14680039
TI  - Different formats for a neurology clerkship do not influence written examination
      scores.
AB  - OBJECTIVE: Changes in health care delivery required substitution of a number of
      alternatives for the traditional inpatient clerkship used in the neurology
      education of fourth-year medical students at the Uniformed Services University of
      the Health Sciences and for third-year medical students from Georgetown
      University. METHODS: We retrospectively analyzed grades on a locally generated
      multiple-choice examination based on a student objective list. Scores from
      students rotating on ambulatory neurology, neurosurgery, child neurology,
      neurorehabilitation, and rotations at other military hospitals over a 2-year
      period were compared with those achieved by students in a traditional clerkship
      at Walter Reed Army Medical Center. RESULTS: There were no significant
      differences in the grades between any of the groups. CONCLUSIONS: Student
      acquisition of factual material was not influenced by the type of clinical
      experience or by whether the student is in the third or fourth year of medical
      school.

PMID- 14680040
TI  - Intubating laryngeal mask airway versus laryngoscopy and endotracheal intubation
      in the nuclear, biological, and chemical environment.
AB  - OBJECTIVE: Intubation is a difficult skill under normal circumstances and more so
      with a limited visual field such as wearing a protective mask in a chemical or
      biological incident. This study sought to determine whether successful intubation
      using the intubating laryngeal mask airway (ILMA) under protective mask
      conditions was equivalent to standard endotracheal intubation. METHODS: A pilot
      study was conducted using emergency medicine personnel. Participant's attempted
      intubation of a manikin while wearing a standard U.S. Army M-40 protective mask.
      Two attempts were performed with each method. RESULTS: One hundred percent of the
      ILMA placements were successful with only 78% success with endotracheal
      intubation (p = 0.1). Time to successful intubation and ventilation was
      significantly less for the ILMA versus endotracheal intubation (p = 0.005).
      CONCLUSION: This study suggests that under simulated chemical and biological
      conditions using an M-40 protective mask, intubation is accomplished faster and
      with more success with the ILMA.

PMID- 14680041
TI  - Developing meaningful metrics of clinical productivity for military treatment
      facility anesthesiology departments and operative services.
AB  - Comparing clinical productivity is important for strategic planning and the
      evaluation of resource allocation in any large organization. This process of
      benchmarking performance allows for the comparison of groups with similar
      characteristics. However, this process is often difficult when comparing the
      operative service productivity of large and small military treatment facilities
      because of the significant heterogeneity in mission focus and case complexity.
      However, in this article, we describe the application of a new method of
      benchmarking operative service productivity based on normalizing data for
      operating room sites, cases, and total American Society of Anesthesiologists
      units produced per hour. We demonstrate how these benchmarks allow for valid
      comparisons of operative service productivity among these military treatment
      facilities and how the data could be used in expanding or contracting operating
      locations. In addition, these benchmarks are compared with those derived from the
      use of this system in the civilian sector.

PMID- 14680042
TI  - Public health model for Dental Specialty MEDRETE.
AB  - OBJECTIVE: Dental readiness training exercises constitute one form of a specialty
      medical readiness and training exercise (MEDRETE). Traditional dental missions
      have been a part of general MEDRETEs and have focused care on extractions and the
      provision of oral hygiene instructions. This article describes the tenets of a
      prevention-based dental humanitarian mission to Honduras in 2002. MATERIALS AND
      METHODS: The U.S. Army Southern Command requested a Dental Specialty MEDRETE for
      fiscal year 2002. A site visit revealed the absence of water fluoridation, high
      levels of dental disease, and a desire to have an American dental team perform
      the dental readiness training exercises at the Escuala Lempira, a low-income
      elementary school in the Honduran capital city of Tegucigalpa. RESULTS: The U.S.
      Army Dental Command in conjunction with the 257th Medical Company (Dental
      Services) performed a pediatric dental readiness training exercises in
      Tegucigalpa March 4-15, 2002. In over 9 treatment days, there were 369 patient
      encounters totaling 1,593 treatment procedures. In keeping with the preventive
      focus of the mission, 514 dental occlusal sealants were provided compared with
      only 90 extractions. Over dollar 76,000 in dental services was provided.
      CONCLUSIONS: The 2002 Honduran Dental Specialty MEDRETE represented a changing
      paradigm from extraction-based dental missions toward prevention-based missions.
      With this philosophical shift in focused care, Dental Specialty MEDRETEs have the
      ability to enhance the oral health of children, including those not fortunate
      enough to have received direct interventional dentistry.

PMID- 14680043
TI  - Quality assessment of primary health care in a military setting.
AB  - PURPOSE: The aim of this study was to analyze the quality of primary care in
      Israeli Defense Forces primary care clinics and physicians (PCPs) and to test the
      hypotheses that: (1) the quality of primary care provided in battalions is higher
      than that provided by other primary care providers and (2) the evaluation of a
      specific PCP within the framework of the quality assessment program results in an
      improved score during a second evaluation. METHODS: Teams of two physicians
      carried out the control process. Each primary care clinic is evaluated in a
      standardized manner by filling a prospectively established form. Five parameters
      are examined: (1) direct inspection of the PCP, (2) medical record audit, (3)
      high-risk patients' management evaluation, (4) evaluation of secondary health
      care characteristics, and (5) medical staff guidance evaluation. The various
      clinics and physicians evaluated were classified as: battalion clinics, division
      and brigade clinics, training center clinics, and home-front clinics. RESULTS:
      Between the years 1999 and 2001, 149 primary care clinics and 250 PCPs were
      evaluated. Seventy-four PCPs (29.6%) were evaluated twice. Battalion clinics
      scored higher than the other clinics. PCPs evaluated twice had significantly
      better quality assessment results at the second encounter. CONCLUSIONS: Quality
      of primary health care is the highest in battalion troops clinics. We interpret
      the increase in quality assessment scores from one examination to the other as an
      index of improvement resulting from the feedback given to the providers.

PMID- 14680044
TI  - Apparent exacerbation of Hansen's disease despite appropriate antimicrobial
      therapy.
AB  - In 1991, the World Health Organization and its member states resolved to reduce
      the global prevalence of Hansen's disease (leprosy) by at least 90%. Despite its
      waning prevalence, however, the disease remains endemic in parts of Africa, Asia,
      and Latin America. Moreover, imported cases are occasionally encountered
      innonendemic areas. This fact, coupled with the current tempo of overseas
      deployments, makes it imperative that military physicians familiarize themselves
      with both the presentation and potential complications of Hansen's disease. Here,
      we present the case of a soldier referred to Walter Reed Army Medical Center for
      apparent worsening of his disease despite appropriate antibiotic therapy. On
      evaluation, the patient was diagnosed with reversal reaction, an immune-mediated
      phenomenon resembling disease exacerbation and requiring prompt intervention to
      avert lasting sequelae. Following the case presentation, we discuss the clinical
      manifestations, pathophysiology, and management of reversal reactions as well as
      the related entity erythema nodosum leprosum.

PMID- 14680045
TI  - Postural control after a 2-mile run.
AB  - Postural control is essential for normal daily activities. It is also a crucial
      requirement for athletic events and activities. Deterioration in this postural
      control mechanism is termed postural instability and results in increased
      postural sway. Decrements in postural sway have been documented following a 15.5
      mile run. It remains to be seen whether a shorter distance run will cause a
      similar decrease in postural control. Therefore, the purpose of this study was to
      assess the effects of a 2-mile run on postural sway in healthy subjects. Forty
      four healthy subjects were assigned to an experimental group (2-mile run) or a
      control group. Postural sway was measured before and after the run with the
      Biodex Stability System Overall Stability Index and a clinical balance test
      called the Military Academy Stance Test. There was a significant before-after run
      Biodex Stability System Overall Stability Index (p < 0.05) and Military Academy
      Stance Test index (p < 0.05) increase in the experimental group. There was no
      significant change for the control group. It was concluded that a 2-mile run does
      produce a significant increase in postural sway as measured using the Biodex
      Stability System Overall Stability Index and Military Academy Stance Test.

PMID- 14680047
TI  - Antibiotics in tactical combat casualty care 2002.
AB  - Care of casualties in the tactical combat environment should include the use of
      prophylactic antibiotics for all open wounds. Cefoxitin was the antibiotic
      recommended in the 1996 article "Tactical Combat Casualty Care in Special
      Operations." The present authors recommend that oral gatifloxacin should be the
      antibiotic of choice because of its ease of carriage and administration,
      excellent spectrum of action, and relatively mild side effect profile. For those
      casualties unable to take oral antibiotics because of unconsciousness,
      penetrating abdominal trauma, or shock, cefotetan is recommended because of its
      longer duration of action than cefoxitin.

PMID- 14680046
TI  - Mental health evaluations of U.S. Air Force basic military training and technical
      training students.
AB  - A 2000 report by Staal, Cigrang, and Fiedler and a 1998 report by Cigrang,
      Carbone, Todd, and Fiedler described the attrition of U. S. Air Force basic
      military trainees due to mental health disorders for the year 1997. This article
      looks at the population of Air Force basic military trainees and technical
      training school students located at the same base during the year 2001. In
      addition, we look at the effect of allowing basic trainees and those in technical
      school to refer themselves for mental health evaluations as opposed to only
      evaluating those referred by secondary sources. Primary results of the data
      analysis suggest that mental health-related separation rates for calendar year
      2001 basic military trainees are consistent with past years at 4.2%. For both
      basic trainees and technical school training students, adjustment disorders and
      depressive disorders are the top diagnostic categories related to recommendation
      for separation.

PMID- 14680048
TI  - Diagnosis of militarily relevant diseases using oral fluid and saliva antibodies:
      fluorescence polarization immunoassay.
AB  - This laboratory is developing fluorescence polarization (FP) methods as
      diagnostic tools to assay antibodies in saliva and other oral fluids. FP provides
      quantitation of molecular interaction, such as antigen-antibody binding, of a
      single, small-volume sample in real time and without prior separation of
      components such as blood cells. There is potential for wide-spread use of these
      homogeneous assays as noninvasive tests, especially as more compact, simplified
      fluorescence polarimeters become available. FP tests can be designed that are
      applicable to a wide spectrum of microorganisms and may be used in a clinic or
      far-forward deployed setting to aid in diagnosis of disease or verification of
      vaccination. Rapid salivary diagnostics, including FP, have been identified by
      the Office of Naval Research as requirements for future naval capabilities in
      basic and applied medical research for warfighter protection in casualty
      prevention. The applications of FP salivary diagnostics for determination of
      tuberculosis exposure and of anthrax immunization status are discussed as
      examples.

PMID- 14680049
TI  - Attitudes and knowledge about continuous oral contraceptive pill use in military
      women.
AB  - OBJECTIVE: The goal of this study was to determine attitudes toward oral
      contraceptive pill (OCP)-induced amenorrhea among U.S. Army women. METHODS: A
      volunteer sample (N = 154) of Army Active Duty, Reserve, and National Guard women
      completed an anonymous survey. RESULTS: Desire for temporary amenorrhea was high
      with 86% (+/- 6%, 95% confidence interval [CI]) and 83% (+/-6%, 95% CI) desiring
      amenorrhea during field training and deployments, respectively. Fifty-four
      percent were unaware that OCPs can induce amenorrhea; only 7% (+/-4%, 95% CI)
      have used this practice during deployment. If made available with education, 49%
      (+/-8%, 95% CI) would use this practice. Logistic burdens of menstruation were
      associated with higher rates of desirability for OCP use with soldiers desiring
      OCPs rating their inconveniences significantly higher than those who did not
      desire OCPs (p < 0.05). CONCLUSION: Although a significant number of soldiers
      desire OCP-induced amenorrhea, a large deficit in knowledge exists. Routine
      education as an Army-wide standard is warranted.

PMID- 14680050
TI  - Smoking behavior of Greek warship personnel.
AB  - The results from a study undertaken to assess the smoking behavior of Greek
      warship personnel found that of the 274 participants, ages 19 to 38 years, 59.5%
      were current smokers who started the habit between the ages of 15 and 21 years.
      However, 33.1% of these current smokers started smoking after entering the Greek
      Navy. There were statistically significant associations between the habit of
      smoking and the occurrences of respiratory tract infections, alcohol consumption,
      lack of aerobic exercise during leisure time, and educational level of the
      personnel. Another significant association was between the age of introduction
      into the habit of smoking and the number of cigarettes smoked daily, with the
      level of education being a contributing factor. The method of entry into the
      Greek Navy and the rank held made a significant contribution to the time period
      of initiation into the habit of smoking. The impact of military life on the
      smoking behavior of the shipboard personnel is discussed and suitable
      intervention strategies have been recommended.

PMID- 14680051
TI  - Land mine injuries: a study of 708 victims in North Iraq and Cambodia.
AB  - OBJECTIVE: The aim of this study was to explore the effect of low-cost
      prehospital trauma systems on trauma outcome in land mine victims and to study
      prehospital risk indicators for better triage of land mine injuries. METHODS: A 5
      year prospective study of the effect of in-field advanced life support provided
      by local paramedics was conducted in mine-infested areas in North Iraq and
      Cambodia. RESULTS: After implementation of a rural rescue system, there was a
      significant reduction in trauma mortality from 26.2% in 1997 to 11.8% in 2001
      (95% confidence interval for difference, 5.1%-23.6%). The mortality rate was
      significantly higher in fragmentation mine victims, 25.2%, as compared with blast
      mine victims, 5.7% (95% confidence interval for difference, 14.4%-24.6%). The
      severity of associated fragment injuries in patients with traumatic amputations
      is a solid risk predictor (area under the curve in receiver operating
      characteristics plots > 0.9). CONCLUSIONS: Low-cost prehospital trauma systems
      improve trauma outcome in land mine victims where prehospital transit times are
      high. The fragment wounds represent the main challenge for trauma care providers.

PMID- 14680053
TI  - Physician assistants in the Canadian Forces.
AB  - Canada is struggling with burgeoning health care access problems. At the same
      time, this nation may be overlooking an available resource to help address
      specific physician shortages. The services of more than 130 physician assistants
      in the Canadian Department of National Defense are used to off-set and amplify
      physician services. Their extensive education and training, along with their
      international experience in war-torn areas, dealing with wounded and ill military
      personnel, refugees, civilians, epidemics, and other health care problems make
      them particularly valuable assets. Yet, upon discharge from military service and
      reentry into the civilian sector, they are left without the legislation and
      formal recognition as a health care provider that would enable them to use these
      skills to help improve medical care access. This study provides the first
      description of the training and activity of Canadian physician assistants.

PMID- 14680052
TI  - Health-related quality of life of U.S. military personnel: a population-based
      study.
AB  - OBJECTIVE: This study evaluated the association between military service and
      health-related quality of life (HRQOL), using a large, population-based sample of
      U.S. adults. METHODS: Participants in the 2000 Behavioral Risk Factor
      Surveillance System were characterized as active duty personnel (N = 1,163),
      reserves (N = 1,055], veterans (N = 22,558), or no military service (N =
      141,620). HRQOL was described by sex and military status. Logistic regression was
      used to calculate sex-specific adjusted odds ratios. RESULTS: Active duty men
      were more likely than men without military service to report 14 or more days of
      activity limitation, pain, and not enough rest in the past 30 days. Reserve
      personnel reported better overall HRQOL than nonmilitary participants, and no
      difference in HRQOL was observed between veterans and persons with no military
      service. CONCLUSIONS: Recommendations are made to monitor HRQOL of active duty
      and reserve personnel over time and to include HRQOL measures in military-based
      surveys of active duty troops.

PMID- 14680054
TI  - Croatian Medical Corps in Bosnia and Herzegovina during the 1992-1995 war.
AB  - OBJECTIVE: The purpose of this study was to review the establishment and
      operation of the Croatian Medical Corps in Bosnia and Herzegovina in the 1992
      1995 war. METHODS: We analyzed pertinent documents available to one of the
      authors (B.I.) who served on the Headquarter of the Corps, the study of the 17
      published articles describing medical activities in various parts of Bosnia and
      Herzegovina during the war, as well as other relevant medical-military
      literature. RESULTS: The Corps functioned effectively and, in fact, served as a
      new health care system for the Croats in Bosnia and Herzegovina. It was
      initiated, planned, and operated voluntarily by members of the medical community,
      established before the defense forces, and later incorporated within them, but
      retaining its autonomy. CONCLUSIONS: The development of the Corps represents a
      unique phenomenon in the history of military medicine.

PMID- 14680055
TI  - Vascularisation of the cerebellar nuclei in Akkaraman sheep.
AB  - This study reports an anatomical study of the vascular supply in 20 Akkaraman
      sheep cerebelli from adult subjects of both sexes. The origin and branching
      pattern of the cerebellar artery vascularising the cerebellar nuclei were studied
      by gross dissection and vascular injection. Then dissection was performed and
      vessels nourishing the cerebellar nuclei were documented. Four bilaterally
      symmetrical cerebellar nuclei were determined as nucleus lateralis cerebelli,
      nucleus interpositus lateralis cerebelli, and nucleus interpositus medialis
      cerebelli and nucleus fastigii from lateral to medial side. It has been
      previously confirmed that vascularisation of the cerebellar nuclei is carried out
      by intermediary branches of the rostral cerebellar artery and the caudal
      cerebellar artery. However, this study has confirmed that the caudal cerebellar
      artery has no contribution in the vascularisation of the cerebellar nuclei.

PMID- 14680056
TI  - Immunolocalisation of serotonin, gastrin, somatostatin and glucagon in entero
      endocrine cells of the goose (Anser anser).
AB  - The processes of digestion in the avian gastrointestinal tract depend on
      sophisticated control systems that co-ordinate secretion of digestive juices and
      movement of the luminal contents. In the current study, the distribution of
      serotonin-, gastrin-, glucagon- and somatostatin-immunoreactive endocrine cells
      was investigated by immunocytochemical methods in the intestinal tract of the
      goose. The number of cells immunoreactive for each antiserum was evaluated in
      different regions of the intestinal tract. Serotonin-, glucagon- and somatostatin
      immunoreactive endocrine cells were seen throughout the intestinal tract, but
      somatostatin-immunoreactive cells were not detected in the colon of the goose.
      Gastrin-immunoreactive cells were detected only in the duodenum, jejunum and
      colon mucosa. It is concluded that the distribution pattern of the entero
      endocrine cells in the goose is similar to that of most of the mammalian and
      other poultry species.

PMID- 14680057
TI  - Antibiotic resistance of staphylococci from humans, food and different animal
      species according to data of the Hungarian resistance monitoring system in 2001.
AB  - Based on data of the Hungarian resistance monitoring system the antibiotic
      resistance of Staphylococcus strains of human and animal origin was studied. No
      methicillin-resistant staphylococci harbouring mecA gene were isolated from
      animals in 2001. Penicillin resistance, mediated by penicillinase production, was
      the most frequent among Staphylococcus aureus strains isolated from humans (96%),
      from bovine mastitis (55%), from foods (45%) and from dogs. In staphylococci
      isolated from animals low resistance percentages to aminoglycosides (0-2%),
      fluoroquinolones (0.5-3%) and sulphonamides (0.5-4%) were found but in strains
      isolated humans these figures were higher (1-14%, 5-18% and 3-31%, respectively).
      The most frequent antibiotic resistance profiles of strains isolated from animals
      and food were penicillin/tetracycline, penicillin/lincomycin and
      penicillin/lincomycin/tetracycline. Penicillin/tetracycline resistance was
      exhibited by strains from mastitis (3), samples from the meat industry (31),
      poultry flocks (1), poultry industry (1), noodle (1) and horses (2).
      Penicillin/lincomycin resistance was found in 10 Staphylococcus strains from
      mastitis, 1 from the dairy industry, 1 from the meat industry and 6 from dogs.
      Isolates from mastitis (2), from the dairy industry (2), from pigs (1), from the
      meat industry (1) and from poultry (1) harboured
      penicillin/lincomycin/tetracycline resistance pattern. Multiresistant strains
      were usually isolated only from one and sometimes from two animal species;
      therefore, the spread of defined resistant strains (clones) among different
      animal species could not be demonstrated. These results also suggest that the
      transfer of antibiotic resistance of S. aureus from animals to humans probably
      occurs less frequently than is generally assumed.

PMID- 14680058
TI  - Wild boars (Sus scrofa) as reservoirs of Brucella suis biovar 2 in Croatia.
AB  - This work presents the results of findings for brucellosis in wild boars and
      domestic swine in two regions of Croatia. In the region of Djakovo the blood
      samples of 211 wild boars were analysed and in 29.4% of the samples serologically
      positive reactions were established. In the same region the blood samples of 1080
      domestic swine on pastures were also analysed and positive serological reactions
      were established in 12.3%. In the regions around Lonjsko Polje the blood samples
      of 53 wild boars were analysed and in 22.6% of them positive serological
      reactions were established. On several locations around Lonjsko Polje the blood
      samples of 901 domestic swine were serologically analysed and 13.5% of the swine
      were found to be seropositive. Bacteriological analyses of submitted materials
      from 24 wild boars resulted in isolation of Brucella from seven (29.2%) samples,
      and from 43 samples originating from domestic swine that had aborted and had been
      serologically positive, Brucella were isolated from 25 (58.1%) swine, as well as
      from 10 (62.5%) out of 16 aborted piglets. In all the isolates Brucella suis
      biovar 2 was identified. Wild boars are carriers and reservoirs of Brucella suis
      biovar 2 in Croatia.

PMID- 14680059
TI  - Comparative study of beta-tricalcium phosphate mixed with platelet-rich plasma
      versus beta-tricalcium phosphate, a bone substitute material in dentistry.
AB  - Animal experiments were carried out with osteoconductive bone substitute beta
      tricalcium phosphate (beta-TCP), with the aim of assessing the effects of the
      growth factors synthesised by thrombocytes on the speed of beta-TCP incorporation
      and on the quality of newly formed bone. The question to be answered was the
      extent to which platelet-rich plasma (PRP) accelerated the resorption of beta-TCP
      and the formation of new bone. Two teeth were removed symmetrically from each
      side of the mandible of 12 Beagle dogs; the resulting cavities were filled on one
      side with beta-TCP alone, and on the other side with a mixture of beta-TCP + PRP
      (obtained from autologous blood). The quality of the newly formed bone and the
      effects of this PRP were studied by histological and histomorphometric methods.
      In week 6, bone formation was already more effective when PRP was applied in
      comparison with beta-TCP alone, and in week 12 the growth was significantly
      greater. The results demonstrate that the use of PRP accelerates the remodelling
      of new bone created by beta-TCP.

PMID- 14680060
TI  - Turbinate atrophy evaluation in pigs by computed tomography.
AB  - Computed tomography (CT), a non-invasive visualisation technique was applied for
      imaging the bony structures of the nasal cavity of pigs, and compared to the
      traditional scoring system of turbinate atrophy in swine. Twenty-three 27-week
      old pigs representing various stages of turbinate atrophy were used. Nasal
      structures were visually scored on CT scans and transversal cuts of the noses at
      the level of the first upper premolar teeth using the same scoring system in both
      cases. A tissue/air area ratio was also determined based on density differences.
      A highly significant correlation was found between visual scoring of CT images
      and transversal cuts of pig noses (r = 0.98, p < 0.0001) as well as between
      visual scoring of CT images and tissue/air area ratio determination (r = -0.82, p
      < 0.0001).

PMID- 14680061
TI  - Occurrence of atypical myxomatosis in Central Europe: clinical and virological
      examinations.
AB  - An outbreak of the atypical form of myxomatosis struck a rabbit farm in Hungary.
      The animals had previously been vaccinated with a vaccine containing Shope rabbit
      fibroma virus strain. The disease appeared in winter when the presence of
      mosquitoes and fleas is not common. The virus was isolated from an eyelid
      specimen of a naturally infected rabbit. The surviving animals were observed for
      four weeks, blood samples were collected and, after euthanasia, organ specimens
      were also examined by morphological methods including pathology and electron
      microscopy. Serum samples were examined by virus neutralisation for antibodies.
      Genetic analysis of the isolated virus was carried out by polymerase chain
      reaction (PCR) and direct sequencing. The primers were designed on the basis of
      the major envelope gene (Env) of the Lausanne reference strain in the GenBank.
      The viral proteins were examined by SDS-PAGE. The isolated virus (ref. no.:
      BP04/2001) was able to infect the susceptible animals directly, by contact. The
      disease was characterised by respiratory symptoms of the upper tracheal tract,
      conjunctivitis and high mortality by the 11th-14th day. Aerogenic infection with
      strain BP04/2001 resulted in 100% morbidity among the susceptible animals.
      Sequencing of the amplified 400-bp-long DNA revealed 97% homology with the Env
      gene of the Lausanne strain, which proves that strain BP04/2001 is a variant of
      the Lausanne strain having been enzootic throughout Europe. The live vaccine
      strain used in Hungary against myxomatosis, which is also a Lausanne-derived
      strain, protected the animals. According to the protein analysis a protein of 200
      kDa in size is not expressed in strain BP04/2001. This is the first report on
      atypical myxomatosis in Central Europe. The virus spreads by airborne
      transmission and may cause severe losses in the rabbit population.

PMID- 14680062
TI  - Metabolic changes induced by regular submaximal aerobic exercise in meat-type
      rabbits.
AB  - Pannon White growing rabbits (a group of 8) were exposed to treadmill exercise (3
      9 m/s, 1.2-1.6 km/day) twice a day for 4 weeks, while additional 8 animals, kept
      inactive, were assigned as the control group. Weekly, 12 hours after exercise,
      venous blood was taken for serum metabolite and enzyme activity measurements.
      Total serum protein, albumin and creatinine levels significantly increased during
      the second half of the training, as compared to the control group.
      Triacylglycerol levels in the exercised group as compared to controls, however,
      were higher only after the first and the fourth weeks of the experiment. Resting
      non-esterified fatty acid (NEFA) concentration of the trained rabbits was lower
      at the end of the trial. On the other hand, there were no significant
      differences, as compared to the respective controls, in serum urea, total and HDL
      cholesterol levels. At the end of the exercise alkaline phosphatase activity was
      higher and total lactate dehydrogenase activity was lower in the trained rabbits.
      Serum alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl
      transpeptidase activities were not changed, while creatine kinase activity was
      slightly lower in the trained group. The serum cortisol concentration was not
      different in the trained and control rabbits.

PMID- 14680063
TI  - Beneficial effects of alternative lighting schedules on the incidence of ascites
      and on metabolic parameters of broiler chickens.
AB  - The beneficial effects of different lighting programmes on the incidence of
      ascites was investigated in an experiment with 360 three-day-old male broiler
      chickens. At 3 days of age, chicks were randomly divided over three rooms in a
      high-altitude farm, 2000 m above sea level. During days 14 to 28 ambient
      temperature decreased during the night but the minimum temperature did not
      descend below 15 degrees C. In the first room the continuous lighting schedule
      (CL, 23L:1D) was maintained and in the second room an intermittent lighting
      schedule (IL, 1L:3D), repeated six times daily, was imposed from 3 days of age.
      In the third room, an increasing photoperiod schedule (IP, 4 to 14 days, 6L:18D;
      15 to 21 days, 10L:14D; 22 to 28 days, 14L:10D; 29 to 35 days, 18L:6D; 36 to 42
      days, 23L:1D) was provided. Mortality associated with right ventricular failure
      and ascites was numerically lower in birds reared under the IL and IP schedules
      compared to birds reared under the CL schedule, which can be attributed to the
      temporary reduction in relative growth and feed intake in IL and IP birds. It was
      concluded that the beneficial effect of lighting schedules could be due to a
      reduced metabolic rate as a consequence of the altered growth trajectory, as also
      reflected in the lower haematocrit and plasma T3 levels of IL and IP birds
      compared to CL birds.

PMID- 14680064
TI  - Fractional excretion of electrolytes during pre- and postpartum periods in cows.
AB  - In this study, fractional excretions (Fe) of sodium (Na), potassium (K), chloride
      (Cl), calcium (Ca), magnesium (Mg) and phosphorus (PO4) were examined with the
      aim to demonstrate interactions between fractional excretions of these
      electrolytes within each period and relate them to electrolyte metabolism in
      clinically normal cows at different stages of lactation and dry period. The
      material of this study consisted of 20 clinically healthy Holstein-Friesian cows
      of the same age and milk yield. Blood and urine samples were collected on 190
      200th, 240-250th and 270-280th days of pregnancy and on days 1-7th, 35-45th and
      75-85th after calving, altogether 6 times. An increase was observed in FeCa and
      FeMg during the transition from the lactation to the dry period (p < 0.05), and a
      decrease in FeCa (p < 0.05), FeMg (p < 0.01) in the 2nd month of the dry period.
      FePO4 and FeMg, respectively, increased on levels of p < 0.01 and p < 0.05, while
      FeCa decreased on a level of p < 0.05 after gestation compared to the level
      before gestation. FeNa and FeK showed a decrease of p < 0.001 and p < 0.01,
      respectively, between the 1st and 2nd months of the dry period, while after
      gestation this value showed an increase in FeNa (p < 0.05) and FeK (p < 0.01).
      FeCl increased significantly (p < 0.05) only from postpartum to the 1st month of
      lactation. There was a strong positive correlation between FeNa and FeCl in all
      of the periods. It was concluded that there were significant changes in the Fe of
      Na, K, Cl, Ca, PO4 and Mg before parturition and during lactation; these changes
      could have an important role in assessing renal function and electrolyte balance.

PMID- 14680065
TI  - Experimental vascular graft for liver transplantation.
AB  - Hepatic artery thrombosis is a major cause of graft failure in liver
      transplantation. Use of donor interponates are common, but results are
      controversial because of necrosis or thrombosis after rejection. Reperfusion
      injury, hypoxia and free radical production determinate the survival. The aim of
      the study was to create an 'ideal' arterial interponate. Autologous, tubular
      graft lined with mesothelial cells, prepared from the posterior rectus fascia
      sheath, was used for iliac artery replacement in eight mongrel dogs for six
      months under immunosuppression. Patency rate was followed by Doppler ultrasound.
      Eight grafts remained patent and another two are patent after one year. The
      patency rate was good (median Doppler flow: 370 cm/sec) and there was no
      necrosis, thrombosis or aneurysmatic formation. The grafts showed viable
      morphology with neoangiogenesis, appearance of elastin, smooth muscle and
      endothelial cells. Electron microscopy showed intact mitochondrial structures
      without signs of hypoxia. Tissue oxygenation was good in all cases with normal (<
      30 ng/ml) myeloperoxidase production. In conclusion, this autologous graft
      presents good long-term patency rate. Viability, arterialisation and low
      thrombogenicity are prognostic factors indicating usability of the graft in the
      clinical practice without the risk of rejection. Further investigations such as
      cell cultures and standardisation are necessary.

PMID- 14680066
TI  - Operation technique and healing process of telescopic ileocolostomy in dogs.
AB  - The healing process of telescopic anastomoses was found in an animal experiment
      with 12 mongrel dogs. After the division of vessels an ileal segment of different
      length was invaginated into the lumen of the colon using single-layer interrupted
      sutures. The following four groups were used: Group A (n = 3): end-to-side
      ileocolostomy, single-layer interrupted suture (invagination length: 0 mm),
      survival time: 21 days. Group B (n = 3): invagination length: 20 mm, survival
      time: 7 days. Group C (n = 3): invagination length: 10 mm, survival time: 21
      days. Group D (n = 3): invagination length: 20 mm, survival time: 21 days. At the
      end of the above survival times the anastomosis area was removed. The bursting
      pressure was measured and morphological as well as histological examinations were
      performed. In each case the 0-day look-alikes of anastomoses were performed using
      the remnant bowels, and bursting pressure measurements were done on these models
      as well. Anastomosis leakage did not occur. The serosal layer of the intracolonic
      part of the ileum disappeared during the healing process. The free surface of the
      intracolonic ileal segment became covered by the sliding mucosa of the colon and
      the prolapsing mucosa of the ileum. The following could be concluded after the
      experiments: The inner pressure tolerance of a telescopic ileocolostomy promptly
      after preparation is better than in case of another single-layer anastomosis.
      This fact results in increased safety against leakage on the first postoperative
      days. The inner pressure tolerance of the telescopic ileocolostomy increases
      during the healing process and it does not depend on the length of the
      invaginated part (0 day-20 mm: 56 mmHg +/- 6, Group A: 252 +/- 39, Group B: 154
      +/- 19, Group C: 249 +/- 20, Group D: 298 +/- 2). There is no difference in
      pressure tolerance between the telescopic and the end-to-side single-layer
      interrupted anastomoses after the healing process. The invaginated section within
      the lumen of the large intestine does not suffer ischaemic or any other kind of
      damage. This inexpensive and simple anastomosis technique could be useful in the
      veterinary surgical practice as well.

PMID- 14680067
TI  - Characterisation of Hungarian porcine circovirus 2 genomes associated with PMWS
      and PDNS cases.
AB  - The authors report the data of the first survey on the incidence of post-weaning
      multisystemic wasting syndrome (PMWS) and porcine dermatitis and nephropathy
      syndrome (PDNS) in Hungary. A PCR method specific for the detection of porcine
      circovirus 2 (PCV-2) was developed, which proved to be suitable for diagnostic
      purposes. PCR screening of organ samples from pigs suspected to be affected with
      PMWS or PDNS revealed the presence of PCV-2 in 80% of the cases. Six PCV-2
      genomes from Hungarian isolates were completely sequenced. Phylogenetic
      comparison with all the available PCV-2 sequences showed that porcine
      circoviruses circulating in Hungary are more variable than in several other
      European countries. Two Hungarian strains clustered together with the Spanish
      strains forming a distinct group; two others fell in a common group with the
      French, UK, and Dutch strains, whereas another two strains showed the closest
      relationship to two of the three known German PCV-2 sequences.

PMID- 14680068
TI  - The burden of lung disease in Europe: why a European White Book on lung disease?

PMID- 14680069
TI  - Is heart rate variability the simple solution to diagnose sleep apnoea?

PMID- 14680070
TI  - Idiopathic pulmonary fibrosis: a treatable disease?

PMID- 14680071
TI  - Combination therapy for chronic obstructive pulmonary disease: one size fits all?

PMID- 14680072
TI  - Hospital-acquired pneumonia: coverage and treatment adequacy of current
      guidelines.
AB  - The American Thoracic Society (ATS) guideline for hospital-acquired pneumonia
      (HAP) released in 1996 and the Trouillet classification published in 1998 supply
      different rational foundations for the classification of patients with HAP and
      for the selection of initial antibiotic therapy. The aims of this study were to
      assess the level of bacterial coverage and to assess and validate the adequacy of
      antibiotic strategy of each of these classifications. Intensive care unit
      admitted patients (n=71) with suspicion of HAP were evaluated. The ATS and
      Trouillet classifications demonstrated an accuracy to predict the causative
      microorganism of 91% and 83% respectively. The ATS and Trouillet antibiotic
      treatment recommendations were adequate in 79% and 80% of the patients,
      respectively. The microorganisms implicated in the treatment inadequacy of the
      ATS guideline were Pseudomonas aeruginosa (n=3), Acinetobacter baumanii (n=1),
      Stenotrophomonas maltophilia (n=1) and methicillin-resistant Staphylococcus
      aureus (n=1). P. aeruginosa was implicated with Trouillet treatment inadequacy.
      The current recommendations for empirical antibiotic treatment of hospital
      acquired pneumonia (American Thoracic Society and Trouillet) showed a good
      ability to predict the involved pathogen. However, considering the resistance
      pattern of the isolated pathogens, both classifications demonstrated a rather
      lower treatment adequacy; the main reason was the failure to treat highly
      resistant strains.

PMID- 14680073
TI  - Clara cell protein as a biomarker for ozone-induced lung injury in humans.
AB  - Exposure to ozone (O3) impairs lung function, induces airway inflammation and
      alters epithelial permeability. Whilst impaired lung function and neutrophilia
      have been observed at relatively low concentrations, altered lung epithelial
      permeability is only seen after high-dose challenges. The appearance of Clara
      cell protein (CC16) in serum has been proposed as a sensitive marker of lung
      epithelial injury. Here, the use of CC16 as an injury biomarker was evaluated
      under a controlled exposure to O3 and the relationship between this marker of
      lung injury and early lung function decrements was investigated. Subjects (n=22)
      were exposed on two separate occasions to 0.2 parts per million O3 and filtered
      air for 2 h. Blood samples were drawn and lung function assessed at 2 h pre
      exposure, immediately before and immediately after exposure as well as 2 and 4 h
      postexposure. O3 increased CC16 serum concentrations at 2 h (12.0+/-4.5 versus
      8.4+/-3.1 microg x L(-1)) and 4 h postexposure (11.7+/-5.0 versus 7.9+/-2.6
      microg x L(-1)) compared with air concentrations. Archived samples from O3
      studies utilising the same design indicated that this increase was sustained for
      up to 6 h postexposure (9.1+/-2.6 versus 7.1+/-1.7 microg x L(-1)) with
      concentrations returning to baseline by 18 h (7.7+/-2.9 versus 6.6+/-1.7 microg x
      L(-1)). In these studies, the increased plasma CC16 concentration was noted in
      the absence of increases in traditional markers of epithelial permeability. No
      association was observed between increased CC16 concentrations and lung function
      changes. To conclude, Clara cell protein represents a sensitive and noninvasive
      biomarker for ozone-induced lung epithelial damage that may have important uses
      in assessing the health effects of air pollutants in future epidemiological and
      field studies.

PMID- 14680074
TI  - Exhaled breath condensate pH is a robust and reproducible assay of airway
      acidity.
AB  - Exhaled breath condensate (EBC) pH is low in several lung diseases and it
      normalises with therapy. The current study examined factors relevant to EBC pH
      monitoring. Intraday and intraweek variability were studied in 76 subjects. The
      pH of EBC collected orally and from isolated lower airways was compared in an
      additional 32 subjects. Effects of ventilatory pattern
      (hyperventilation/hypoventilation), airway obstruction after methacholine,
      temperature (-44 to +13 degrees C) and duration of collection (2-7 min), and
      duration of sample storage (up to 2 yrs) were examined. All samples were
      collected with a disposable condensing device, and de-aerated with argon until pH
      measurement stabilised. Mean EBC pH (n=76 subjects, total samples=741) was 7.7+/
      0.49 (mean+/-SD). Mean intraweek and intraday coefficients of variation were 4.5%
      and 3.5%. Control of EBC pH appears to be at the level of the lower airway.
      Temperature of collection, duration of collection and storage, acute airway
      obstruction, subject age, saliva pH, and profound hyperventilation and
      hypoventilation had no effect on EBC pH. The current authors conclude that in
      health, exhaled breath condensate pH is slightly alkaline, held in a narrow
      range, and is controlled by lower airway source fluid. Measurement of exhaled
      breath condensate pH is a simple, robust, reproducible and relevant marker of
      disease.

PMID- 14680075
TI  - Evaluation of bronchoalveolar cells in pulmonary paracoccidioidomycosis.
AB  - To investigate the local immune response, the cellular infiltrate and cytokine
      levels were analysed in bronchoalveolar lavage (BAL) from patients with pulmonary
      paracoccidioidomycosis. The group consisted of 19 patients aged 34-65 yrs. The
      diagnosis was confirmed by demonstration of the fungus in the sputum or BAL fluid
      and by serological tests. Cytospin preparations showed an increased number of
      lymphocytes and neutrophils in BAL. A higher number of CD8+ lymphocytes were
      observed in BAL compared with peripheral blood. Alveolar macrophages (AM)
      expressed approximately three-fold more major histocompatibility class II,
      intercellular adhesion molecule-1 and B7-2 molecules on their surfaces than their
      circulating counterparts, indicating that they had differentiated into activated
      macrophages inside the lungs. Cultured AM produced higher levels of interleukin
      (IL)-6, tumour necrosis factor (TNF)-alpha and macrophage inflammatory protein
      (MIP)-1alpha than peripheral blood monocytes. BAL fluid contained low but
      detectable amounts of IL-6, TNF-alpha and MIP-1alpha, and specific antibodies to
      Paracoccidioides brasiliensis, mainly of the immunoglobulin G2 isotype. As
      macrophage inflammatory protein-1alpha was shown to selectively attract CD8+ T
      cells and this population was elevated in bronchoalveolar lavage, the data
      suggest that, besides macrophages, CD8+ T-cells may have an important role in the
      pathogenesis of pulmonary paracoccidioidomycosis.

PMID- 14680076
TI  - Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac
      expression in rats.
AB  - Oxidative stress is involved in the pathogenesis of pulmonary fibrosis, therefore
      antioxidants may be of therapeutic value. Clinical work indicates that N
      acetylcysteine (NAC) may be beneficial in this disease. The activity of this
      antioxidant was examined on bleomycin-induced lung damage, mucus secretory cells
      hyperplasia and mucin Muc5ac gene expression in rats. NAC (3 mmol x kg(-1) x day(
      1)) or saline was given orally to Sprague-Dawley rats for 1 week prior to a
      single intratracheal instillation of bleomycin (2.5 U x kg(-1)) and for 14 days
      postinstillation. NAC decreased collagen deposition in bleomycin-exposed rats
      (hydroxyproline content was 4,257+/-323 and 3,200+/-192 microg x lung(-1) in
      vehicle- and NAC-treated rats, respectively) and lessened the fibrotic area
      assessed by morphometric analysis. The bleomycin-induced increases in lung tumour
      necrosis factor-alpha and myeloperoxidase activity were reduced by NAC treatment.
      The numbers of mucus secretory cells in airway epithelium, and the Muc5ac
      messenger ribonucleic acid and protein expression, were markedly augmented in
      rats exposed to bleomycin. These changes were significantly reduced in NAC
      treated rats. These results indicate that bleomycin increases the number of
      airway secretory cells and their mucin production, and that oral N-acetylcysteine
      improved pulmonary lesions and reduced the mucus hypersecretion in the bleomycin
      rat model.

PMID- 14680077
TI  - Does interferon-gamma improve pulmonary function in idiopathic pulmonary
      fibrosis?
AB  - Idiopathic pulmonary fibrosis (IPF) is a disease with progressive and devastating
      deterioration of lung function and a fatal prognosis, despite aggressive
      therapeutic attempts, which, in the majority of cases are futile. Recently, a
      preliminary study of long-term treatment with interferon (IFN)-gamma1b and low
      dose prednisolone in patients with IPF suggested that IFN-gamma1b treatment may
      improve lung function parameters of patients with IPF. Ever since, specialists in
      respiratory medicine who treat patients with IPF, are called by patients
      demanding treatment with IFN-gamma1b. Therefore, the authors here present another
      prospective investigation of IFN-gamma1b in five patients with IPF. According to
      the previously published design, patients received 200 microg IFN-gamma1b
      subcutaneously three-times per week and 10 mg prednisolone orally for 12 months.
      Two patients stopped IFN-gamma1b treatment after 4 months due to side-effects and
      further lung function deterioration and one patient died 3 months after
      commencement of therapy. In total, pulmonary function improved in only one
      patient during IFN-gamma1b treatment, while four patients deteriorated. To
      conclude, this small series of idiopathic pulmonary fibrosis cases treated with
      interferon-gamma1b and corticosteroids does not support previous data that this
      treatment improves pulmonary function or alters the natural course of idiopathic
      pulmonary fibrosis. Furthermore, in the authors' experience, side-effects of
      interferon-gamma1b treatment can significantly reduce patients' quality of life.

PMID- 14680078
TI  - Maintenance therapy with budesonide and formoterol in chronic obstructive
      pulmonary disease.
AB  - Lung function in chronic obstructive pulmonary disease (COPD) can be improved
      acutely by oral corticosteroids and bronchodilators. Whether clinical improvement
      can be maintained by subsequent inhaled therapy is unknown. COPD patients
      (n=1,022, mean prebronchodilator forced expiratory volume in one second (FEV1)
      36% predicted) initially received formoterol (9 microg b.i.d.) and oral
      prednisolone (30 mg o.d.) for 2 weeks. After this time, patients were randomised
      to b.i.d. inhaled budesonide/formoterol 320/9 microg, budesonide 400 microg,
      formoterol 9 microg or placebo for 12 months. Postmedication FEV1 improved by
      0.21 L and health-related quality of life using the St George's Respiratory
      Questionnaire (SGRQ) by 4.5 units after run-in. Fewer patients receiving
      budesonide/formoterol withdrew from the study than those receiving budesonide,
      formoterol or placebo. Budesonide/formoterol patients had a prolonged time to
      first exacerbation (254 versus 96 days) and maintained higher FEV1 (99% versus
      87% of baseline), both primary variables versus placebo. They had fewer
      exacerbations (1.38 versus 1.80 exacerbations per patient per year), had higher
      prebronchodilator peak expiratory flow, and showed clinically relevant
      improvements in SGRQ versus placebo (-7.5 units). Budesonide/formoterol was more
      effective than either monocomponent in both primary variables.
      Budesonide/formoterol in a single inhaler (Symbicort) maintains the benefit of
      treatment optimisation, stabilising lung function and delaying exacerbations more
      effectively than either component drug alone or placebo.

PMID- 14680079
TI  - Cytokines and dietary energy restriction in stable chronic obstructive pulmonary
      disease patients.
AB  - Tumour necrosis factor (TNF)-alpha has been found to be increased in malnourished
      chronic obstructive pulmonary disease (COPD) patients; however, the main cause of
      this phenomenon remains undetermined. In normal subjects, TNF-alpha production
      may be induced by dietary energy deprivation. The aim of this study was to
      investigate if stable COPD patients present alterations of inflammatory mediators
      after 48 h of dietary energy restriction. Fourteen COPD patients were admitted to
      the hospital while receiving an experimental diet with an energy content of
      approximately one-third of their energy needs. Clinical evaluation, nutritional
      assessment and serum levels of interleukin (IL)-6, TNF-alpha and C-reactive
      protein, and secretion of TNF-alpha by peripheral blood monocytes were assessed
      on admission and after the experimental diet. For reference values of the
      laboratory parameters, blood was collected from 10 healthy, elderly subjects.
      COPD patients showed significantly higher serum concentrations of IL-6 than
      control subjects, however, the experimental diet was not associated with
      statistically significant changes in the inflammatory mediators. The findings of
      this study, although preliminary because of the limited degree and duration of
      the energy restriction, suggest that the elevated levels of tumour necrosis
      factor-alpha, previously described in undernourished or weight-losing chronic
      obstructive pulmonary disease patients, may not be linked to a decrease of
      dietary energy intake.

PMID- 14680080
TI  - Montelukast attenuates the airway response to hypertonic saline in moderate-to
      severe COPD.
AB  - This study assessed the effect of the leukotriene receptor antagonist montelukast
      on hypertonic saline-induced airway obstruction. A total of 29 patients with
      chronic obstructive pulmonary disease (forced expiratory volume in one second
      (FEV1), 42+/-4% predicted) received either 10 mg montelukast and 3 h later
      placebo via metered-dose inhaler (MDI) (M), or placebo and 3 h later 200 microg
      salbutamol (S), or two doses of placebo (P), in a randomised order. Patients
      inhaled salbutamol 1 h after MDI and the challenge was performed 15 min later (3%
      saline, 5 min). Data are given as per cent changes versus baseline. Compared to
      P, S caused significant bronchodilation in FEV1 (7.3%) and forced inspiratory
      volume in one second (FIV1) (4.5%), and M in FIV1 (1.5%). The saline-induced fall
      in FEV1 was lower after M (-5.8%), compared with S (-10.3%) and P (-13.1%). FEV1
      (11.3%) and FIV1 (7.6%) was improved over baseline after recovery by M but not P
      and S. Recovery times regarding FEV1 (8.5 min) and FIV1 (15.2 min) were shortest
      after M, respective values for S being 16.8 and 20.4 min, and for P 15.9 and 21.2
      min. Effects were strongest in patients with low baseline FEV1 and/or inhaled
      corticosteroids. Data from this study indicate beneficial effects of montelukast
      on hypertonic saline-induced airway responses in patients with chronic
      obstructive pulmonary disease, particularly those with severe disease. The major
      effect was an accelerated recovery leading to values above baseline.

PMID- 14680081
TI  - Longitudinal changes in the nature, severity and frequency of COPD exacerbations.
AB  - Exacerbations are an important feature and outcome measure in chronic obstructive
      pulmonary disease (COPD), but little is known about changes in their severity,
      recovery, symptom composition or frequency over time. In this study 132 patients
      (91 male; median age 68.4 yrs and median forced expiratory volume in one second
      (FEV1) 38.4% predicted) recorded daily symptoms and morning peak expiratory flow.
      Patients were monitored for a median of 918 days and 1,111 exacerbations were
      identified. Patients with severe COPD (Global Initiative for Chronic Obstructive
      Lung Disease (GOLD) category III, n=38) had an annual exacerbation frequency of
      3.43 x yr(-1), 0.75 x yr(-1) higher than those with moderate COPD (GOLD II,
      n=94). Exacerbation frequency did not change significantly during the study. At
      exacerbation onset, symptom count increased to 2.23, relative to a baseline of
      0.36 set 8-14 days previously, and this increase rose by 0.05 x yr(-1). Recovery
      to baseline levels in symptoms and FEV1 took longer (0.32 and 0.55 days x yr(
      1)). Sputum purulence at exacerbation became more prevalent over time by 4.1% x
      yr(-1) from an initial value of 17%. The results of this study suggest that over
      time, individual patients have more symptoms during exacerbations, with an
      increased chance of sputum purulence and longer recovery times.

PMID- 14680082
TI  - Predicting sleep apnoea syndrome from heart period: a time-frequency wavelet
      analysis.
AB  - Heart rate fluctuations are a typical finding during obstructive sleep apnoea,
      characterised by bradycardia during the apnoeic phase and tachycardia at the
      restoration of ventilation. In this study, a time-frequency domain analysis of
      the nocturnal heart rate variability (HRV) was evaluated as the single diagnostic
      marker for obstructive sleep apnoea syndrome (OSAS). The predictive accuracy of
      time-frequency HRV variables (wavelet (Wv) decomposition parameters from level 2
      (Wv2) to level 256 (Wv256)) obtained from nocturnal electrocardiogram Holter
      monitoring were analysed in 147 consecutive patients aged 53.8+/-11.2 yrs
      referred for possible OSAS. OSAS was diagnosed in 66 patients (44.9%) according
      to an apnoea/hypopnoea index > or = 10. Using receiver-operating characteristic
      curves analysis, the most powerful predictor variable was Wv32 (W 0.758,
      p<0.0001), followed by Wv16 (W 0.729, p<0.0001) and Wv64 (W 0.700, p<0.0001).
      Classification and Regression Trees methodology generated a decision tree for
      OSAS prediction including all levels of Wv coefficients, from Wv2 to Wv256 with a
      sensitivity reaching 92.4% and a specificity of 90.1% (percentage of agreement
      91.2%) with this nonparametric analysis. Time-frequency parameters calculated
      using wavelet transform and extracted from the nocturnal heart period analysis
      appeared as powerful tools for obstructive sleep apnoea syndrome diagnosis.

PMID- 14680083
TI  - Spectral oscillations of RR intervals in sleep apnoea/hypopnoea syndrome
      patients.
AB  - A recent study has shown that daytime heart rate variability is reduced in
      obstructive sleep apnoea/hypopnoea syndrome (OSAHS) patients. In the present
      study, the hypothesis was that sympathovagal balance around apnoeas/hypopnoeas
      and nocturnal autonomic activity are altered in OSAHS patients. Frequency- and
      time-domain analyses of RR intervals were performed to monitor sympathovagal
      activity noninvasively. Fourteen untreated OSAHS patients and seven healthy
      subjects underwent overnight polysomnography. Low (LF) and total (TF) frequency
      power increased 2 min around the end of apnoeas/hypopnoeas (LF 229+/-38 ms2 TF
      345+/-45 ms2) compared with undisturbed sleep (LF 106+/-18 ms2, TF 203+/-23 ms2).
      The increase in high frequency (HF) power was not significant. LF increase was
      proportionally higher than the HF increase (normalised LF (LFn) 67+/-1 units,
      normalised HF (HFn) 33+/-1 units) compared with undisturbed sleep (LFn 52+/-2
      units, HFn 48+/-2 units). RR duration did not change around apnoeas/hypopnoeas
      (RR 904+/-28 ms). The LF and TF power increase was greater around arousal
      inducing (LF 260+/-45 ms2 TF 390+/-65 ms2) compared with self-terminating (LF
      161+/-31 ms2, TF 249+/-40 ms2) apnoeas/hypopnoeas; the LF and LFn increases were
      significant in both groups compared with undisturbed sleep and HF power
      differences were nonsignificant. RR intervals were longer around self-terminating
      apnoeas/hypopnoeas (RR 914+/-29 ms); the differences were not significant
      compared with undisturbed sleep. RR interval spectral power was not influenced by
      the event type. RR duration decreased (912+/-28 ms) and LF, HF and TF power
      increased (LF 111+/-16 ms2 , HF 62+/-6 ms , TF 173+/-21 ms2) across patients,
      compared with healthy controls (RR 1138+/-91 ms, LF 57+/-3 ms2, HF 35+/-3 ms2, TF
      91+/-6 ms2). LFn and HFn did not change significantly. Sympathetic activity
      increases around apnoeas/hypopnoeas. The recurrent nocturnal fluctuations of
      sympathovagal balance and the overall increase of nocturnal autonomic activity
      may be of importance in the development of cardiovascular disease in sleep apnoea
      patients.

PMID- 14680084
TI  - Microsatellite DNA instability and loss of heterozygosity in bronchial asthma.
AB  - Genetic alterations, such as loss of heterozygosity (LOH) or microsatellite
      instability (MI), have been reported in both malignant and benign disorders. In
      order to identify loci of deoxyribonucleic acid (DNA) mutation in asthma, MI and
      LOH were studied in sputum cells. DNA was extracted from cells in the sputum and
      blood cells of 22 patients with moderate asthma. Cells were analysed for MI and
      LOH using 18 polymorphic markers on chromosome 5q, 6p, 11q, 14q. Microsatellite
      analysis was also performed in six healthy subjects. None of the healthy
      individuals exhibited any genetic alteration. Genetic alterations were found in
      16 of 22 asthmatic patients (73%). In total, 12 (54.5%) patients exhibited LOH
      only, one (4.5%) MI only, while three showed both MI and LOH. The highest
      incidence of LOH and MI was found on chromosome 14q. Mean immunoglobulin E and
      blood eosinophil levels were significantly higher in asthmatics with three or
      more genetic alterations. A high incidence of genetic alterations in the
      deoxyribonucleic acid of the sputum cells was found in asthmatic patients.
      Further studies are needed to identify the role of loss of heterozygosity and
      microsatellite instability in the investigation of genetic susceptibility of
      asthma and thus, in its pathogenesis.

PMID- 14680085
TI  - Can early infection explain the sibling effect in adult atopy?
AB  - Atopy is strongly and inversely related to family size, a pattern which is
      plausibly assumed to reflect a protective effect of early infection. The current
      study tested this hypothesis by case-referent analysis of an adult cohort in the
      UK. The study established that atopy, defined by prick tests to common
      aeroallergens, was less common among those from larger families after adjustment
      for potentially confounding factors. In particular, a higher number of brothers
      appeared to offer protection. The current authors attempted to explain this
      distribution by examining contemporary family-doctor records of early childhood
      infections; and by a number of other indirect indices of early-life "hygiene".
      The sibling effect was unexplained by evidence of infection with either hepatitis
      A or Helicobacter pylori, or by counts of infections or antibiotic prescriptions
      in early life. There was a significant and independent negative association
      between the number of gastrointestinal infections before the age of 5 yrs and the
      odds of atopy. Dog ownership and home moving in early life also displayed
      potentially protective associations. Although the current study replicates the
      finding that atopy is inversely associated with family size this could not be
      explained by documentary or serological evidence of early infection. The findings
      support the suggestion that the "sibling effect" in atopy may not simply reflect
      protection by early infection.

PMID- 14680086
TI  - Lower risk of atopic disorders in whole cell pertussis-vaccinated children.
AB  - This study addressed whether whole cell pertussis-vaccinated children have a
      different risk of atopic disorders compared with children who did not receive
      this vaccination. Data on vaccination status, atopic disorders and child and
      family characteristics of the children of 700 families were collected in this
      retrospective study. A minority of these 700 families refused vaccinations for
      religious reasons. The relation between pertussis-vaccination status and atopic
      disorders was analysed by means of adjusted logistic regression for repeated
      measurements in order to account for the correlation between sibship members. The
      700 families included 1,961 children. Data on vaccination status and atopic
      disorders were available for 1,724 children. Vaccinated children had a reduced
      risk of atopic disorders. Whole cell pertussis vaccination is associated with a
      lower risk of atopic disorders, though other vaccine components (diphtheria,
      tetanus, poliomyelitis) or other vaccinations may also be involved.

PMID- 14680087
TI  - Evaluation of airway wall thickness and air trapping by HRCT in asymptomatic
      asthma.
AB  - The aim of this study was to examine the relationship between the structural
      changes in large and small airways in asymptomatic asthmatics quantified by high
      resolution computed tomography (HRCT) and airflow obstruction. The bronchial wall
      thickness at the trunk of the apical bronchus (B1) of the right upper lobe was
      used for assessment of the large airways. Air trapping, evaluated by the ratio of
      the average CT-determined values for the bilateral upper and lower lung segments
      at full expiration to that at full inspiration (E/I ratio), was used for
      assessment of the small airways. Measurements were obtained with a helical HRCT
      in 24 asymptomatic asthmatics followed by optimal treatment with inhaled and/or
      oral corticosteroids for >6 months. Prior (20-30 min) to the HRCT examination,
      all patients were given an inhaled bronchodilator. The ratio of airway wall
      thickness to outer diameter (T/D) and the percentage wall area (WA%) at the B1
      bronchus and the E/I ratio were significantly greater for the 14 asthmatics with
      deficient reversible airflow obstruction (forced expiratory volume in one second
      (FEV1) <80% prediced or FEV1/forced vital capacity <70% after bronchodilator
      inhalation) than for the 10 asthmatics with normal spirometry and seven normal
      subjects. T/D, WA%, and E/I ratio showed significant negative correlations with
      FEV1 % pred after bronchodilator inhalation. The E/I ratio also showed
      significant positive correlations with T/D, WA%, and residual volume/total lung
      capacity. These findings suggest that, in spite of optimal treatment, structural
      changes in both large and small airways may simultaneously occur in asthmatics
      with deficient reversible airflow obstruction.

PMID- 14680088
TI  - Evaluation of ventilation maldistribution as an early indicator of lung disease
      in children with cystic fibrosis.
AB  - Many children with cystic fibrosis (CF), receiving modern, aggressive CF care,
      have normal spirometry results. This study aimed to see if homogeneity of
      ventilation distribution is impaired early in the course of CF lung disease, and
      if ventilation inhomogeneity is a more frequent finding than abnormal spirometry
      in children benefiting from modern CF care. The study compared spirometry
      findings to two indices of ventilation inhomogeneity (mixing ratio (MR) and lung
      clearance index (LCI)) from multiple-breath inert gas washout in 43 children with
      CF, aged 3-18 yrs, and 28 healthy children. In total, 10/43 CF subjects (23%) had
      reduced forced expiratory volume in one second (FEV1) and 14/34 (41%) showed
      abnormal maximum expiratory flow at 25% of forced vital capacity (MEF25). In
      contrast, MR was abnormal in 31/43 (72%) and LCI in 27/43 (63%). MR was abnormal
      in 22/33 CF subjects with normal FEV1, versus 0/28 controls (p<0.001), and
      abnormal MR was found in 10/20 CF subjects with normal MEF25, versus 0/22
      controls (p<0.001). Nine of the 10 CF subjects with reduced FEV1 and 12/14 with
      abnormal MEF25 showed abnormal MR. Inert gas washout discloses airway dysfunction
      in the majority of children with cystic fibrosis with normal lung function judged
      by spirometry. These findings suggest that multiple-breath inert gas washout is
      of greater value than spirometry in detecting early cystic fibrosis lung disease.

PMID- 14680089
TI  - Incidence and short-term outcome of acute lung injury in mechanically ventilated
      children.
AB  - The aim of this study was to determine the incidence and short-term outcome of
      mechanically ventilated children suffering from acute lung injury (ALI) on a
      paediatric intensive care unit (PICU). Between January 1 1998 and January 1 2000,
      all mechanically ventilated children were evaluated using the criteria of an
      American-European Consensus Conference. Of the 443 children eligible for
      analysis, 44 (9.9%) were diagnosed as suffering from ALI. Of these, 79.5%
      developed the acute respiratory distress syndrome (ARDS); 54.5% (24 of 44)
      fulfilled the ARDS criteria at inclusion and 25% (11 of 44) later. PICU mortality
      for ALI was 27.3% (12 of 44) and within the ARDS subgroup 31.4% (11 of 35). Of
      the 12 children who died, 11 had ARDS; the main cause of death was cerebral
      damage (seven of 12). Acute lung injury and acute respiratory distress syndrome
      are rare diseases on a paediatric intensive care unit with a high mortality. Most
      of the children with acute lung injury develop acute respiratory distress
      syndrome. In the acute respiratory distress syndrome subgroup, mortality is
      higher than in the acute lung injury nonacute respiratory distress syndrome
      subgroup. Further investigations should confirm prognostic factors (e.g.
      respiratory parameters) for prediction of outcome.

PMID- 14680091
TI  - Variation of CD8+ T-lymphocytes around the bronchial internal perimeter in
      chronic bronchitis.
AB  - The variation of CD8+ cells has been determined around the internal perimeter of
      intrapulmonary bronchi in smokers with chronic bronchitis (CB), and the amount of
      tissue required to confidently estimate the true mean has been calculated. Lung
      specimens were obtained from 10 smokers with CB. Paraffin sections of
      intrapulmonary bronchi were immunostained and CD8+ cells counted in the
      epithelium and subepithelium in up to 10 sequential 1-mm segments around the
      internal perimeter of each airway. The percentage of counts falling between +/
      20% of the final mean was 43.0% for epithelium and 40.9% for subepithelium. In
      90% of subjects, the cumulative mean was stable after examination of
      subepithelial tissue associated with 5 mm of reticular basement membrane. There
      is considerable variation in the counts of CD8+ cells between adjacent 1-mm
      airway mucosal segments in chronic bronchitis. In order to achieve a
      representative count and to maximise statistical power to detect differences
      between study populations, subepithelial tissue including a minimum of 5 mm of
      reticular basement membrane length should be examined.

PMID- 14680090
TI  - Aspirin-sensitive rhinitis-associated changes in upper airway innervation.
AB  - Aspirin-sensitive rhinitis is the manifestation of aspirin intolerance in the
      upper respiratory tract. The disease represents a pseudoallergy against aspirin
      or related nonsteroidal anti-inflammatory drugs. As a major immunomodulatory role
      for airway innervation has been proposed in airway inflammatory diseases, the
      present study assessed changes in human nasal mucosa innervation in patients with
      aspirin-sensitive rhinitis in comparison to a control group. Immunohistochemistry
      for protein gene product 9.5, tachykinins, calcitonin gene-related peptide,
      vasoactive intestinal peptide (VIP) and neuropeptide tyrosine was performed on
      cryostats sections of nasal mucosa and neuropeptide containing nerves were
      examined independently using a score grading. In comparison to the control, the
      aspirin-sensitive rhinitis group had a significant increase of VIP-like
      immunoreactivity in mucosal nerve fibres. In contrast to constant numbers of mast
      cells, highly significant increases in the numbers of eosinophils were found in
      the group of aspirin-sensitive rhinitis patients. In summary, the present
      quantification of neuropeptide-immunoreactivity of mucosal nerves demonstrated
      differences in the human nasal mucosa innervation between nonrhinitic and aspirin
      sensitive rhinitic individuals. These differences may reflect a
      pathophysiological role of upper airway innervation in pseudoallergic reactions.

PMID- 14680092
TI  - A method to preserve sputum for delayed examination.
AB  - Examination of sputum cell counts is limited by the need to process samples
      within hours of expectoration. The validity and repeatability of a method to
      preserve sputum for delayed processing and examination were investigated in this
      study. Portions of selected sputum from 39 subjects were dispersed with
      dithiothreitol (routine method), or were fixed in a dithiothreitol-formaldehyde
      mixture for 48-72 h before dispersal with trypsin (preservation method). Total
      and differential cell counts using the two methods were compared; within-method
      repeatability of the preservation method was also examined. The intraclass
      correlation coefficient (ICC) for total cell counts and percentage of
      eosinophils, neutrophils and macrophages in sputum processed by the two methods
      was 0.89, 0.86, 0.91 and 0.90, respectively. Within-method repeatability (ICC) of
      the preservation method for the same cellular indices was 0.99, 0.94, 0.97 and
      0.97, respectively. The interobserver repeatability for eosinophils, neutrophils
      and macrophages was 0.96, 0.97 and 0.97 using the preservation method, and 0.96,
      0.99 and 0.99 using the routine method, respectively. This method of sputum
      preservation and dispersal is valid, reliable and convenient, and may be used for
      delayed processing and examination.

PMID- 14680093
TI  - Face mask spirometry and respiratory pressures in normal subjects.
AB  - Spirometry and maximal respiratory pressures are pulmonary function parameters
      commonly used to evaluate respiratory function. Prediction values are available
      for conventional lung function devices using a standard tube or flanged type of
      mouthpiece connection. This equipment is not suitable for patients with facial or
      buccal muscle weakness, because of air leakage around the mouthpiece. A face mask
      was used for the portable lung function devices used in the neuromuscular
      department. The aim of this study was to compare the face mask and the
      conventional mouthpiece for the measurement of spirometry and of respiratory
      pressures in 22 healthy subjects. Values obtained with the conventional
      mouthpiece differed significantly from values obtained with the face mask. With
      the mask, forced vital capacity and forced expiratory volume in one second were
      200 mL lower, and maximal expiratory pressure was 3.2 kPa lower than with the
      mouthpiece. Subsequently, new prediction values for face mask spirometry and
      maximal respiratory pressures were obtained from 252 other healthy subjects, from
      which new prediction equations were derived. It was concluded that the face mask
      connection to the lung function device is a valid alternative, is easy to use and
      is most useful to monitor changes in patients. This study confirms the importance
      of appropriate prediction equations, depending on subject-instrument interfaces.

PMID- 14680094
TI  - Post-transplant bronchiolitis obliterans.
AB  - Over the last decade, improvements in surgical techniques, lung preservation,
      immunosuppression, and management of ischaemia/reperfusion injury and infections
      have made intermediate-term survival after lung transplantation an achievable
      goal. However, chronic allograft dysfunction in the form of bronchiolitis
      obliterans remains a major hurdle that threatens both the quality of life and
      long-term survival of the recipients. It affects up to 50-60% of patients who
      survive 5 yrs after surgery, and it accounts for >30% of all deaths occurring
      after the third postoperative year. This article discusses the alloimmune
      dependent and -independent risk factors for bronchiolitis obliterans, the current
      understanding of the pathogenesis of bronchiolitis obliterans based on results of
      animal and human studies, the clinical staging of the complication, strategies
      that may contribute to the prevention and/or early detection of bronchiolitis
      obliterans, and suggestions for future research.

PMID- 14680095
TI  - High-altitude pulmonary hypertension: a pathophysiological entity to different
      diseases.
AB  - Pulmonary hypertension is a hallmark of high-altitude pulmonary oedema (HAPE) and
      of congestive right heart failure in subacute mountain sickness (SMS) and chronic
      mountain sickness (CMS) in the Himalayas and in the end-stage of CMS (Monge's
      disease) in the Andes. There are studies to suggest that transmission of
      excessively elevated pulmonary artery pressure and/or flow to the pulmonary
      capillaries leading to alveolar haemorrhage is the pathophysiological mechanism
      of HAPE. In the Himalayas, HAPE was successfully prevented by extending the
      acclimatisation period from a few days to 5 weeks, however, this did not prevent
      the occurrence of congestive right heart failure after several weeks of stay at
      6,000 m. This leads to the concept that rapid remodelling of the small
      precapillary arteries prevents HAPE but not the development of right heart
      failure in SMS and CMS. Unresponsiveness of pulmonary hypertension to oxygen at
      high altitude and its complete resolution only after weeks of stay at low
      altitude suggest that structural rather than functional changes are its
      pathophysiological mechanism. Since pulmonary hypertension at high altitude is
      the driving force leading to high-altitude pulmonary oedema and "high-altitude
      right heart failure" in newcomers and residents of high altitude, the authors
      propose to adjust current terminology accordingly.

PMID- 14680096
TI  - The forced oscillation technique in clinical practice: methodology,
      recommendations and future developments.
AB  - The forced oscillation technique (FOT) is a noninvasive method with which to
      measure respiratory mechanics. FOT employs small-amplitude pressure oscillations
      superimposed on the normal breathing and therefore has the advantage over
      conventional lung function techniques that it does not require the performance of
      respiratory manoeuvres. The present European Respiratory Society Task Force
      Report describes the basic principle of the technique and gives guidelines for
      the application and interpretation of FOT as a routine lung function test in the
      clinical setting, for both adult and paediatric populations. FOT data, especially
      those measured at the lower frequencies, are sensitive to airway obstruction, but
      do not discriminate between obstructive and restrictive lung disorders. There is
      no consensus regarding the sensitivity of FOT for bronchodilation testing in
      adults. Values of respiratory resistance have proved sensitive to bronchodilation
      in children, although the reported cutoff levels remain to be confirmed in future
      studies. Forced oscillation technique is a reliable method in the assessment of
      bronchial hyperresponsiveness in adults and children. Moreover, in contrast with
      spirometry where a deep inspiration is needed, forced oscillation technique does
      not modify the airway smooth muscle tone. Forced oscillation technique has been
      shown to be as sensitive as spirometry in detecting impairments of lung function
      due to smoking or exposure to occupational hazards. Together with the minimal
      requirement for the subject's cooperation, this makes forced oscillation
      technique an ideal lung function test for epidemiological and field studies.
      Novel applications of forced oscillation technique in the clinical setting
      include the monitoring of respiratory mechanics during mechanical ventilation and
      sleep.

PMID- 14680098
TI  - Noseclips in children performing spirometry.

PMID- 14680097
TI  - A 71-yr-old male with increasing dyspnoea, cough and an intrathoracic mass.

PMID- 14680099
TI  - Distribution of the common tick, Ixodes ricinus (Acari: Ixodidae), in different
      vegetation types in southern Sweden.
AB  - The aim of this study was to investigate whether differences in Ixodes ricinus
      (L.) nymphal relative density exist among different vegetation types in southern
      Sweden. Nymphal I. ricinus were sampled in southeastern Scania in southern Sweden
      during June-August 1997. A total of 110-180 25-m2 samples were taken by blanket
      dragging from each of nine different vegetation types. There was a highly
      significant difference in nymphal abundance between the open areas as one group
      and the forested areas as another group (P < 0.0001). Vegetation types that
      differed significantly in median nymphal abundance from all other vegetation
      types were pine forest (16 nymphs/100 m2) and beech forest (40 nymphs/100 m2). No
      significant differences in median nymphal density were revealed among mixed
      deciduous forest, alder forest, oak forest, and hazel forest (28-32 nymphs/100
      m2), or among dry meadow, meadow, and heath (0 nymphs/100 m2). Forestation of
      open areas is likely to lead to increased I. ricinus abundance and disease risk.

PMID- 14680100
TI  - Malaria vectors, epidemiology, and the re-emergence of Anopheles darlingi in
      Belem, Para, Brazil.
AB  - An evaluation of malaria transmission and epidemiology in the Amazonian city of
      Belem over the last 70 years shows that (1) Anopheles darlingi, reported to be
      eradicated in 1968, reappeared in the mid 1990s, with a marked increase in
      abundance between 1997 to 1999 in two of three districts sampled; (2) An.
      darlingi and An. aquasalis are each implicated in current malaria transmission in
      different districts of the city; (3) mosquito species diversity (in Anopheles
      subgenus Nyssorhynchus) has increased from two in the 1930s to six in the 1940s
      to 10 in the 1990s; (4) there is no overall correlation between malaria case
      incidence and human population size from 1940 to 1996 in Belem; (5) however, the
      total number of malaria cases has increased significantly since the late 1970s
      and over the short term from 1993 to 1999; and (6) interestingly, the short term
      increases are due solely to cases of Plasmodium vivax infection; cases of P.
      falciparum malaria are declining (significantly for Para state only). The
      reappearance of An. darlingi may be a result of the continued expansion of Belem
      into the surrounding forest in the 1990s. In the absence of preventative
      measures, we predict an increase in local outbreaks of malaria in the DAENT and
      DAICO districts where the population sizes of An. darlingi are increasing.

PMID- 14680101
TI  - Factors affecting immatures of Ochlerotatus taeniorhynchus (Diptera: Culicidae)
      in San Diego County, California.
AB  - The effects of tide, temperature, rainfall, and salinity on the occurrence and
      abundance of immatures (instars and pupae) of the black salt marsh mosquito,
      Ochlerotatus taeniorhynchus (Wiedemann), were examined at a tidal pond in the
      Tijuana Estuary during 1996-1998. Immatures were found between May and early
      September. Tide had the greatest influence on immatures of this mosquito. Eggs
      eclosed when tides averaged 1.96 +/- 0.10 (SD) m (1.83-2.19) 1-3 d before a flood
      tide. Eclosion averaged once every 14.4 d during 1996 (nine broods) and 1997
      (eight broods) and once every 20.2 d during 1998 (six broods). Immatures were
      most abundant during late May-early August when tides were usually > or = 2.0 m,
      and mean (+/-SD) pond temperature was 27.6 +/- 2.6 degrees C (23.8-33.9) and
      salinity was 44.6 +/- 13.9 g/kg (33-95). Temperature primarily influenced egg
      diapause and influenced rate of development of immatures. Increased amounts of
      seasonal rainfall during 1997-1998 (42.9 cm: caused by El Nino), compared with
      1995-1996 (11.4 cm) and 1996-1997 (17.3 cm), may have increased the mortality of
      overwintering eggs and/or diluted salinity of the substrate making it less
      conducive for oviposition.

PMID- 14680102
TI  - Meteorologically mediated diurnal questing of Ixodes scapularis and Amblyomma
      americanum (Acari: Ixodidae) nymphs.
AB  - Questing Ixodes scapularis Say and Amblyomma americanum (L.) nymphs were
      collected in the field by drag sampling to determine whether ticks would be
      collected in greater numbers during certain times of the day and under certain
      ambient meteorological conditions. Ticks were collected hourly for 16 h on 4 d
      and counts were contrasted with simultaneous measurements of ambient temperature
      and relative humidity, and with similar measurements made within the leaf litter.
      Peak numbers of questing I. scapularis and A. americanum nymphs were collected at
      distinctly different times of day, suggesting that the two species were
      responding to different environmental conditions. Both species demonstrated
      responses to diel changes in local meteorological conditions. Numbers of ticks
      were correlated with ambient temperature and humidity and with conditions
      recorded in the leaf litter that appeared to play a significant role in mediating
      questing behavior of both species. The time of day when tick sampling is
      conducted might significantly bias population estimates for sympatric species and
      the assessment of tick-borne disease transmission risk.

PMID- 14680104
TI  - Interpopulation variability among Panstrongylus megistus (Hemiptera: Reduviidae)
      from Brazil.
AB  - Comparisons were made among Panstrongylus megistus (Burmeister) from three areas
      of Brazil (Bahia, Minas Gerais, and Santa Catarina), where populations differ
      with regard to their degree of association with human dwellings. The following
      characters were studied: morphology of the eggs and the male genitalia;
      morphometry of the head and thorax; isoenzyme profile; enzymatic activity of the
      alpha-glycerophosphate dehydrogenase (alpha-GPDH); and cytogenetics. In general,
      differences were observed in the weight, diameter, and length of the egg among
      Bahia, Minas Gerais, and Santa Catarina populations. Differences were not
      observed in the architecture of the egg exochorion. The size of the median
      process of the pygophore of the male genitalia of individuals from Bahia differed
      from the other two populations. The Minas Gerais population presented the largest
      number of denticles in the endosome process. The morphometry of the head and
      thorax differentiated Santa Catarina from the Bahia and Minas Gerais populations.
      Phosphoglucomutase (EC 5.4.2.2., PGM) was the only enzyme out of 11 that showed
      polymorphism; the population from Minas Gerais was most polymorphic, whereas the
      population from Santa Catarina was monomorphic. Study of the alpha-GPDH activity
      and cytogenetics did not reveal differences among the three populations. Analysis
      of all the characters studied together with information on these three
      populations from previous publications allowed a phenogram to be constructed. Two
      distinct groups were evident, one represented by Santa Catarina and the other by
      Bahia and Minas Gerais. Considering the greater variability of the Minas Gerais
      and Bahia populations, we propose the inclusion of these states within the area
      of origin of P. megistus.

PMID- 14680103
TI  - Habitat preferences and phenology of Ochlerotatus triseriatus and Aedes
      albopictus (Diptera: Culicidae) in southwestern Virginia.
AB  - Recently, the number of reported human cases of La Crosse encephalitis, an
      illness caused by mosquito-borne La Crosse virus (LAC), has increased in
      southwestern Virginia, resulting in a need for better understanding of the virus
      cycle and the biology of its vectors in the region. This study examined the
      spatial and temporal distributions of the primary vector of LAC, Ochlerotatus
      triseriatus (Say), and a potential secondary vector, Aedes albopictus (Skuse).
      Ovitrapping surveys were conducted in 1998 and 1999 to determine distributions
      and oviposition habitat preferences of the two species in southwestern Virginia.
      Mosquitoes also were collected for virus assay from a tire dump and a human La
      Crosse encephalitis case site between 1998 and 2000. Oc. triseriatus and Ae.
      albopictus were collected from all ovitrap sites surveyed, and numbers of Oc.
      triseriatus eggs generally were higher than those of Ae. albopictus. Numbers of
      Oc. triseriatus remained high during most of the summer, while Ae. albopictus
      numbers increased gradually, reaching a peak in late August and declining
      thereafter. In Wise County, relative Ae. albopictus abundance was highest in
      sites with traps placed in open residential areas. Lowest numbers of both species
      were found in densely forested areas. Ovitrapping during consecutive years
      revealed that Ae. albopictus was well established and overwintering in the area.
      An oviposition comparison between the yard and adjacent forest at a human La
      Crosse encephalitis case site in 1999 showed that Ae. albopictus preferentially
      oviposited in the yard surrounding the home, but Oc. triseriatus showed no
      preference. LAC isolations from larval and adult collections of Oc. triseriatus
      females from the same case site indicated the occurrence of transovarial
      transmission.

PMID- 14680105
TI  - Spatial and temporal variation in kinship among Anopheles gambiae (Diptera:
      Culicidae) mosquitoes.
AB  - Genetic relatedness (kinship) among Anopheles gambiae Giles female mosquitoes was
      assessed using microsatellite loci in five locations across Africa and in nine
      samples taken between 1994 and 1999 in western Kenya. We assessed variation among
      samples in kinship as well as the effect of distance on kinship. Relatedness
      within populations was low, and differences among samples taken at various times
      from one locale and from different locales were minimal. Mosquitoes collected
      from the same compound were slightly more closely related than those collected
      from different compounds. Our results suggest that newly emerged female siblings
      move relatively short distances into a few nearby compounds for blood feeding,
      but that they lay eggs in a more distant location. Kinship decreased nonlinearly
      with increasing distance. The strongest relationship between kinship and distance
      was observed for mosquitoes collected 0-3 km apart (-0.014/km, P < 0.001). The
      effect of distance decreased with increasing distance between mosquitoes; at 7 km
      or more, the kinship/distance slope approached zero and the intercept became
      negative, suggesting that beyond this range kinship does not decline with
      distance. This distance may thus represent the upper limit of the diameter of the
      basic reproductive unit. Nevertheless, the effect of distance on kinship is weak,
      reflecting extensive dispersal. Because females mate within days after emergence
      from larval habitats, where the likelihood of mating with a sibling is presumably
      highest, we propose a slight inbreeding effect.

PMID- 14680106
TI  - Genetic differentiation of Aedes aegypti (Diptera: Culicidae), the major dengue
      vector in Brazil.
AB  - In 2000, Brazil reported 180,137 cases of dengue, approximately 80% of the total
      in the Americas. However, little is known about gene flow among the vector
      populations in Brazil. Random amplified polymorphic DNA (RAPD) was used to study
      the genetic structure of Aedes aegypti in 15 populations from five states, with a
      range extending 2,800 km. An analysis of 47 polymorphic RAPD loci estimated gene
      flow at the macro- (different states) and micro- (different cities) geographical
      levels. Genetic polymorphism was high (H(S) = 0.274), and high levels of genetic
      differentiation existed both between different states (G(ST) = 0.317) and between
      cities or neighborhoods in each state (G(ST) = 0.085-0.265). These values are
      higher than those described for any other populations of A. aegypti.

PMID- 14680107
TI  - The Chagas vector, Triatoma dimidiata (Hemiptera: Reduviidae), is panmictic
      within and among adjacent villages in Guatemala.
AB  - Trypanosoma cruzi, the hemoflagellate parasite and cause of Chagas disease in
      Latin America, is carried by Triatomine vectors, principally Triatoma dimidiata
      and Rhodnius prolixus in Central America. To assist control efforts and to
      understand the epidemiology of the disease in Guatemala, the population genetics
      of T. dimidiata was analyzed among three houses within a village and two adjacent
      villages in Guatemala. Eleven Randomly Amplified Polymorphic DNA-polymerase chain
      reaction (RAPD-PCR) primers were screened and three used to amplify bands, 29 of
      which were scored, from T. dimidiata DNA of approximately 50 bugs per house from
      three houses within a village and from 66 and 33 bugs, respectively, from
      adjacent villages. Results show very small genetic distances among the three T.
      dimidiata subpopulations from the houses (D = 0.013-0.022) and the two villages
      (D = 0.0199). The amount of differentiation among houses (fixation index, F(ST))
      was also very small, F(ST) = 0.025 among the houses and the two villages F(ST) =
      0.019. These fixation indices give an average number of mating migrants per
      generation (Nm) of 9.7 (among houses) and 12 (among villages). Average
      heterozygosity (H) appears to be high, ranging from H = 0.299-0.325 among the
      houses and H = 0.273 among the villages. The low genetic distance and fixation
      indices, and high heterozygosity suggest that the subpopulations in the houses
      and in the adjacent villages are not reproductively isolated but are in fact, one
      large panmictic population. Therefore the geographic coverage necessary for
      effective control must include, at least, the area encompassing adjacent
      villages.

PMID- 14680108
TI  - Effects of mating on oogenesis induced by amino acid infusion, amino acid
      feeding, or blood feeding in the mosquito Anopheles stephensi (Diptera:
      Culicidae).
AB  - Hemocoel infusion of an amino acid mixture at a concentration of 7.5% and 10%
      (wt:vol) for 24 h rarely activated ovarian development in either mated or unmated
      females of Anopheles stephensi Liston. Infusion of either concentration mixture
      for 48 h into unmated females was also scarcely stimulatory, but the same 48 h
      infusion into mated females resulted in ovarian maturation in 25% (7.5% mixture)
      or in 78% (10% mixture) of the infused specimens. Similarly, feeding on an amino
      acid mixture (7.5%) containing sugar induced 44% ovarian maturation among mated
      females, while only 3% of unmated females showed matured oocytes. The increase of
      hemolymph amino acid concentration levels may be one of the essential factors for
      oogenesis of An. stephensi, and mating enhances ovarian development, especially
      in females ingesting poor meals. However, some additional factor(s) may be
      included for full development comparable to that induced by blood meals.

PMID- 14680109
TI  - Prevalence and levels of permethrin resistance in Pediculus humanus capitis De
      Geer (Anoplura: Pediculidae) from Buenos Aires, Argentina.
AB  - Permethrin has been used extensively for control of Pediculus humanus capitis De
      Geer (Anoplura: Pediculidae) in Argentina since 1990, resulting in the
      development of resistance to this and other pyrethroids. This resistance was
      first detected in some field populations in 1997. A survey for resistance in
      Buenos Aires in 2001 revealed significant resistance levels in lice on children
      at 24 of 26 (92.3%) schools. When compared with a previously unexposed reference
      population, resistance ratios (RRs) obtained by exposing the insects to filter
      papers impregnated with permethrin ranged from 2 to 60 in 10 (39%) of the
      schools. RRs in the remaining 14 (61%) populations were too great to not be
      measured with the filter paper method (RR > 88.7). As an alternative, we used
      topical applications of 0.1 microl of acetone solution of permethrin on the
      dorsal abdomen of adults and third instars. This topical method, which has not
      been previously reported for head lice, was capable of quantifying higher levels
      of resistance. Highly resistant populations had RRs from 162.5 to 655.2. When
      applied to populations with low and intermediate levels of resistance, results
      from the filter paper and topical application methods were highly correlated, and
      RRs from topical application were higher than those from the filter paper method.
      Results from the combination of the two methods indicated that head lice among
      Buenos Aries school children are highly resistant to permethrin, and the
      resistance is widespread.

PMID- 14680110
TI  - Record of Evlachovaea sp. (Hyphomycetes) on Triatoma sordida in the state of
      Goias, Brazil, and its activity against Triatoma infestans (Reduviidae,
      Triatominae).
AB  - A fungal isolate was detected on a dead Triatoma sordida (Stal) collected in a
      peridomestic area in central Brazil. The fungus belongs to Evlachovaea Borisov
      and Tarasov, a new genus that was recently described in Russia. The isolate seems
      to be a third species and the second new and undescribed species from Brazil. The
      fungus was shown to be active against Triatoma infestans (Klug) third-instar
      nymphs at a humidity close to saturation. However, activity was reduced at a
      lower humidity (75%). Values of LC50 varied between 1.1 x 10(5) and 1.5 x 10(4)
      conidia/cm2 treated surface, 15 and 20 d after fungal application and incubation
      at humidity close to saturation. This new fungus may have a potential for
      biological control of peridomestic Chagas' disease vectors during the rainy
      season.

PMID- 14680111
TI  - Field evaluation of a lethal ovitrap for the control of Aedes aegypti (Diptera:
      Culicidae) in Thailand.
AB  - In 1999 and 2000 we evaluated a lethal ovitrap (LO) for the control of Aedes
      aegypti (L.) in three villages in Ratchaburi Province, Thailand. Two blocks of 50
      houses (a minimum of 250 m apart) served as treatment and control sites in each
      village, with each house in the treatment area receiving 10 LOs. Thirty houses in
      the center of each treatment and control block were selected as sampling sites,
      with larval and adult mosquito sampling initiated when LOs were placed. Sampling
      was conducted weekly in 10 of the 30 houses at each site, with each block of 10
      houses sampled every third week. Sampling continued for 30 wk. Efficacy of the LO
      was evaluated by determining number of containers with larvae and/or pupae per
      house and number of adult mosquitoes collected inside each house. In 1999, the LO
      had a negligible impact on all measures of Ae. aegypti abundance that were
      assessed; however, fungal contamination of insecticide-impregnated strips may
      have been responsible for the low efficacy. In 2000, significant suppression was
      achieved based on changes in multiple entomologic criteria (containers with
      larvae, containers with pupae, and number of adult Ae. aegypti); however, control
      was not absolute and neither immature nor adult Ae. aegypti were ever eliminated
      completely. We conclude that the LO can reduce adult Ae. aegypti populations in
      Thailand; however, efficacy of the LO is lower than desired due primarily to the
      high number of alternative oviposition sites. LO efficacy may be improved when
      used as part of an integrated control program that places emphasis on reduction
      of adjacent larval habitats. Further studies are required to assess this issue.

PMID- 14680112
TI  - Olfactometric evaluation of spatial repellents for Aedes aegypti.
AB  - The spatial repellency responses of Aedes aegypti (L.) to deet, dehydrolinalool
      and linalool were evaluated using a dual port olfactometer. In the absence of
      human attractant mixture, each of the three chemicals resulted in activation
      and/or orientation of mosquitoes to the chemical source. Linalool was the most
      attractive compound. In the presence of human attractant mixture, activation
      and/or orientation of mosquitoes to each of the three chemicals was reduced. We
      compared reductions in mosquito responses to each of the three chemicals, in the
      presence of human attractant mixture, to estimate spatial repellency. As
      expected, lowest spatial repellency (7.3%) was observed using human attractant
      alone. Highest spatial repellency (33.6%) was observed using a combination of
      linalool and dehydrolinalool. Deet did not manifest spatial repellency, whereas
      linalool and dehydrolinalool alone, and in combination, exhibited spatial
      repellency.

PMID- 14680113
TI  - Molecular analysis of a para sodium channel gene from pyrethroid-resistant head
      lice, Pediculus humanus capitis (Anoplura: Pediculidae).
AB  - The problem of pyrethroid-resistance in head lice, Pediculus humanus capitis (De
      Geer), is growing worldwide, and an insensitive sodium channel is suspected as
      the major mechanism of this resistance. We sequenced an open reading frame (ORF)
      encoding for the para-orthologous sodium channel from an insecticide-susceptible
      strain of the body louse, Pediculus humanus humanus (L.), based on conserved
      peptide sequences and a known partial gene sequence. Phenothrin-susceptible and 
      resistant head louse colonies from Japanese were individually analyzed for point
      mutations of the sodium channel cDNA; susceptible head and body lice differed in
      double homozygous synonymous substitutions. The resistant head lice shared 23
      base substitutions homozygously, in which four resulted in amino acid
      substitutions: D11E in the N-terminal inner-membrane segment; M850T in the outer
      membrane loop between segments four and five of domain II; T952I and L955 F in
      the trans-membrane segment five of domain II. The latter two substitutions
      coincided with those of pyrethroid-resistant head lice in the U.S. and U.K. (Lee
      et al. 2000), within the available published information on the peptide
      sequences. The potential mechanisms of head louse pyrethroid-resistance are
      discussed based on the four structural changes of the target molecule.

PMID- 14680114
TI  - Laboratory evaluation of selective pesticides against the storage mite Tyrophagus
      putrescentiae (Acari: Acaridae).
AB  - The storage mite, Tyrophagus putrescentiae (Schrank), is an important source of
      airborne allergens, especially on farms. Three insect growth regulators
      (halofenozide, pyriproxyfen, hexaflumuron), one botanical insecticide
      (azadirachtin) and one naturalyte (spinosad) were tested to assess their efficacy
      against this mite. The organophosphate chlorpyrifos was used as a standard.
      Immature stages and adults were treated with different concentrations of the
      chemicals in diet-incorporation bioassays. All chemicals significantly increased
      the developmental time of immature stages at doses higher than 1,000 ppm.
      Pyriproxyfen and halofenozide yielded mortality rates of immature stages similar
      to that obtained with chlorpyrifos, with values near 100% at 10,000 ppm. At 1,000
      ppm, only halofenozide significantly increased the mortality of immature stages.
      Similarly, adult survival and fecundity were significantly reduced with
      halofenozide at 1,000 ppm, whereas it required 10,000 ppm of chlorpyrifos to
      obtain a significant reduction in survival and fecundity, with no effect observed
      with pyriproxyfen. This data suggests that halofenozide could be a good
      alternative for the control of T. putrescentiae in farming environments.

PMID- 14680115
TI  - Resistance to coumaphos and diazinon in Boophilus microplus (Acari: Ixodidae) and
      evidence for the involvement of an oxidative detoxification mechanism.
AB  - The levels of resistance to two organophosphate acaricides, coumaphos and
      diazinon, in several Mexican strains of Boophilus microplus (Canestrini) were
      evaluated using the FAO larval packet test. Regression analysis of LC50 data
      revealed a significant cross-resistance pattern between those two acaricides.
      Metabolic mechanisms of resistance were investigated with synergist bioassays.
      Piperonyl butoxide (PBO) reduced coumaphos toxicity in susceptible strains, but
      synergized coumaphos toxicity in resistant strains. There was a significant
      correlation between PBO synergism ratios and the coumaphos resistance ratios. The
      results suggest that an enhanced cytochrome P450 monooxygenase (cytP450)-mediated
      detoxification mechanism may exist in the resistant strains, in addition to the
      cytP450-mediated metabolic pathway that activates coumaphos. PBO failed to
      synergize diazinon toxicity in resistant strains, suggesting the cytP450 involved
      in detoxification were specific. Triphenylphosphate (TPP) synergized toxicity of
      both acaricides in both susceptible and resistant strains, and there was no
      correlation between TPP synergism ratios and the LC50 estimates for either
      acaricide. Esterases may not play a major role in resistance to coumaphos and
      diazinon in those strains. Bioassays with diethyl maleate (DEM) revealed a
      significant correlation between DEM synergism ratios and LC50 estimates for
      diazinon, suggesting a possible role for glutathione S-transferases in diazinon
      detoxification. Resistance to coumaphos in the Mexican strains of B. microplus
      was likely to be conferred by both a cytP450-mediated detoxification mechanism
      described here and the mechanism of insensitive acetylcholinesterases reported
      elsewhere. The results of this study also underscore the potential risk of
      coumaphos resistance in B. microplus from Mexico to the U.S. cattle fever tick
      eradication program.

PMID- 14680116
TI  - Insecticide susceptibility status of Anopheles gambiae s.l. (Diptera: Culicidae)
      in the Republic of Cameroon.
AB  - A large-scale survey of Anopheles gambiae Giles, 1902 susceptibility to DDT,
      dieldrin, permethrin, and deltamethrin was conducted in the Republic of Cameroon.
      15 field populations from various geographical areas were tested using World
      Health Organization test kits for adult mosquitoes. The laboratory Kisumu
      susceptible reference strain was tested as a control. Results showed that
      dieldrin and DDT resistance was still present in some populations, and indicated
      permethrin or deltamethrin resistance. Within the Anopheles gambiae complex,
      resistant individuals belonged to An. gambiae s.s. and An. arabiensis species.
      Both M and S molecular forms of An. gambiae s.s. were found resistant. In most of
      resistant populations, the knockdown times were 2-5-folds increased. However,
      none of the surviving mosquitoes was positive to the kdr "Leu-Phe" mutation using
      polymerase chain reaction (PCR) diagnostic test. These results likely suggested
      involvement of other resistance mechanism(s), such as enzyme detoxification or
      kdr "Leu-Ser" mutation. Researches on An. gambiae s.l. resistance should be
      promoted in Cameroon, to improve malaria vector control programs and to implement
      resistance management strategies.

PMID- 14680117
TI  - Methoprene interferes with mosquito midgut remodeling during metamorphosis.
AB  - Many juvenile hormone analogs interfere with insect metamorphosis, a property
      that makes them useful in insect control and as investigatorial tools with which
      to study metamorphic mechanisms. We report that one such analog, methoprene,
      interferes with mosquito metamorphic midgut remodeling. Methoprene treated Aedes
      aegypti (L.), Aedes albopictus (Skuse), and Culex quinquefasciatus (Say) fourth
      instars pupate, but the pupal midguts are morphologically similar to larval
      midguts. The degree of midgut remodeling is affected by the dose of methoprene
      applied and the extent of fourth instar development when methoprene exposure is
      initiated. DNA staining indicates that high methoprene concentrations interfere
      with diploid cell division and programmed death of polytene cells. Lower
      methoprene concentrations do not interfere with diploid cell division but the
      removal of polytene cells is incomplete. The effect of methoprene dose on the
      extent of midgut remodeling correlates well with its effect on pupal and adult
      survival. Metamorphic midgut remodeling offers a mosquito system with which to
      study the effect of ecdysone, juvenile hormone and juvenile hormone analogs on
      metamorphosis. An understanding of the molecular mechanisms by which methoprene
      affects mosquito metamorphosis might lead to the development of more effective
      mosquito control chemicals having fewer deleterious environmental effects and to
      genetic strategies by which mosquito populations might be controlled.

PMID- 14680118
TI  - Effects of wet cleaning with disodium octaborate tetrahydrate on dust mites
      (Acari: Pyroglyphidae) in carpet.
AB  - In a controlled laboratory study, disodium octaborate tetrahydrate (DOT) applied
      to carpets with a carpet-cleaning machine at a rate of 509 ml DOT/8.15 liter
      H2O/100 m2 (two cups DOT/2 gal H2O/100 feet2) reduced survival and population
      growth of live Dermatophagoides farinae and Dermatophagoides pteronyssinus by >
      or = 98% compared with water-cleaned and uncleaned carpets at 8 wk postcleaning.
      Cleaning with DOT was more effective against D. pteronyssinus than D. farinae.

PMID- 14680119
TI  - Infectivity and pathogenicity of a novel baculovirus, CuniNPV from Culex
      nigripalpus (Diptera: Culicidae) for thirteen species and four genera of
      mosquitoes.
AB  - The infectivity and pathogenicity of newly discovered baculovirus, CuniNPV
      (family Baculoviridae, genus Nucleopolyhedrovirus) originally isolated from the
      mosquito Culex nigripalpus Theobald, was evaluated in laboratory bioassys against
      thirteen species and four genera of mosquitoes native to the northeastern U.S.
      Purified virus at a dosage rate of 1.6 x 10(7) occlusion bodies/ml with 10 mM
      Mg2+ added was used in exposures with second through fourth instars at
      temperatures ranging from 17 to 27 degrees C. High infection rates and
      accompanying mortality were achieved in Cx. pipiens L. (83.0-14.4%), Cx. pipiens
      f. molestus (80.4% infection), and Cx. salinarius Coquillett (48.0-43.1%). Cx.
      restuans Theobald was also susceptible but infection rates were lower (21.3
      12.5%). The gross pathology associated with infection was identical to that
      reported in Cx. nigripalpus. Infected larvae were lethargic and were often
      suspended at the water surface. Development of CuniNPV was observed in the nuclei
      of the midgut epitheial cells in the gastric caeca and posterior region of the
      stomach of host larvae. One hundred percent mortality was observed in all larvae
      that exhibited gross symptoms of infection within 4-d p.i. Cx. territans Walker
      (subgenus Neoculex Dyar) was the only Culex mosquito that was not susceptible. No
      infections were obtained with any species of Aedes [Ae. vexans (Meigen)],
      Culiseta [Culiseta morsitans (Theobald)] or Ochlerotatus [Ochlerotatus canadensis
      (Theobald), Oc. cantator (Coquillett), Oc. communis (De Geer), Oc. excrucians
      (Walker), Oc. japonicus (Theobald), Ochlerotatus stimulans (Walker), and
      Ochlerotatus triseriatus (Coquillett)]. The host range of CuniNPV appears to be
      restricted to Culex mosquitoes within the subgenus Culex. An inhibitory effect on
      transmission of CuniNPV was observed when a liver powder/Brewer's yeast mixture
      was used as a source of food reinforcing the critical role of Mg2+ and
      sensitivity of the infection process to the presence other divalent cations
      (Cu2+, Fe2+, and Zn2+) in the larval medium that interfered with the infection
      process. The high infectivity and pathogenicity of CuniNPV for the principal
      vectors of West Nile virus in North America make CuniNPV an attractive candidate
      for future development as a biopesticide.

PMID- 14680120
TI  - Detection of Israel turkey meningo-encephalitis virus from mosquito (Diptera:
      Culicidae) and Culicoides (Diptera: Ceratopogonidae) species and its survival in
      Culex pipiens and Phlebotomus papatasi (Diptera: Phlebotomidae).
AB  - Israel turkey meningo-encephalitis (ITME) virus was detected in pools of
      Ochlerotatus caspius Pallas and Culicoides imicola Kieffer trapped at a turkey
      run at Nir David during an outbreak in August 1995. Experimental membrane feeding
      on a blood ITME suspension showed that Culex pipiens L. became harbored virus for
      at least 14 d. When Phlebotomus papatasi Scopoli were fed on an infected turkey,
      they became infected and harbored the virus for at least 7 d. Because
      Phlebotomines are trapped frequently at turkey runs in Israel, they should be
      suspected as potential vectors of ITME.

PMID- 14680121
TI  - Vector competence of rural and urban strains of Aedes (Stegomyia) albopictus
      (Diptera: Culicidae) from Sao Paulo State, Brazil for IC, ID, and IF subtypes of
      Venezuelan equine encephalitis virus.
AB  - Aedes albopictus (Skuse) is an Asiatic mosquito species that has spread and
      colonized all continents except Antarctica. It has major public health importance
      because it is a potential vector of several pathogens. The objectives of our
      study were to analyze the vector competence of urban and rural strains of Ae.
      albopictus from Sao Paulo State (Brazil) for Venezuelan equine encephalitis virus
      (VEE) subtypes IC, ID, and IF, and to evaluate the effect of infection with
      subtype IC of VEE on mosquito longevity. Both mosquito strains were susceptible
      to subtypes IC and ID, but the infection rate for subtype IF was low. Infection
      and transmission rates of Ae. albopictus for subtype IC were similar to those
      reported for Ochlerotatus taeniorhynchus (Wiedemann). The high infection,
      dissemination, and transmission rates for subtype ID reported for Oc. fulvus
      (Wiedemann) and Culex (Melanoconion) spp. are comparable with those found in this
      study. We found significant differences in the susceptibility to subtype IC
      between rural and urban populations of Sao Paulo. Significant survival rate
      differences were observed between uninfected and infected mosquitoes, but there
      were no differences in survival between rural and urban mosquito strains.

PMID- 14680122
TI  - Transstadial transfer of West Nile virus by three species of ixodid ticks (Acari:
      Ixodidae).
AB  - Larvae and/or nymphs of four species of ixodid ticks, Ixodes scapularis Say,
      Amblyomma americanum (L.), Dermacentor andersoni Stiles, and Dermacentor
      variabilis Say, were fed to completion on laboratory hamsters or mice which had
      been inoculated with a West Nile (WN) virus isolate from Culex pipiens L.
      captured in Connecticut USA. Maximum titers in mice and hamsters were
      approximately 5 and two logs, respectively, lower than recorded (10 logs) in a
      naturally infected American crow, Corvus brachyrhynchos Brehm. WN virus was
      isolated in Vero cell culture from ticks and detected by TaqMan RT-polymerase
      chain reaction (PCR) in ticks that had completed their feeding as larvae or
      nymphs, and in I. scapularis, D. andersoni, and D. variabilis that had molted
      into the next stage of development. Naive hosts, fed upon by nymphs that as
      larvae had fed on viremic hosts, did not become infected. WN virus was isolated
      in Vero cell culture from one female I. scapularis and was detected by TaqMan RT
      PCR in 24 adult I. scapularis, one D. andersoni, and two D. variabilis adults
      that had fed to completion as larvae on viremic hosts and as nymphs on naive mice
      or hamsters. Three species of ixodid ticks acquired WN virus from viremic hosts
      and transstadially passed the virus, but vector competency was not demonstrated.

PMID- 14680123
TI  - Detection of Borrelia burgdorferi, Ehrlichia chaffeensis, and Anaplasma
      phagocytophilum in ticks (Acari: Ixodidae) from a coastal region of California.
AB  - A study was conducted in Santa Cruz County to estimate the prevalence and
      distribution of the agents of Lyme disease, human granulocytic (HGE), and human
      monocytic (HME) ehrlichiosis in 1,187 adult ixodid ticks collected from eight
      public-use recreation areas over a 2-yr period. Borrelia burgdorferi, the
      causative agent of Lyme disease, was detected by a polymerase chain reaction
      (PCR) in 44 of 776 (5.67%) Ixodes pacificus ticks and in 3 of 58 (5.17%)
      Dermacentor variabilis ticks. Anaplasma phagocytophilum, the causative agent of
      HGE, was detected by PCR in 48 (6.19%) I. pacificus ticks and 5 (8.62%) D.
      variabilis ticks. Ehrlichia chaffeensis, the causative agent of HME, was detected
      by nested PCR in just five (0.64%) I. pacificus ticks and four (6.9%) D.
      variabilis ticks. Interestingly, eight (1.03%) I. pacificus ticks were co
      infected with B. burgdorferi and A. phagocytophilum, and just one (0.12%) tick
      was co-infected with B. burgdorferi and E. chaffeensis. Less than 1% of 353
      Dermacentor occidentalis ticks showed evidence of infection with any of the
      agents tested. To our knowledge, this is the first reported identification of A.
      phagocytophilum and E. chaffeensis in D. occidentalis ticks from California This
      study represents the first extensive survey of Lyme and the ehrlichial diseases
      across multiple areas of Santa Cruz County, and suggests that prevalence of B.
      burgdorferi in Santa Cruz County may be higher than other areas of the state.

PMID- 14680124
TI  - The effects of bird feeders on Lyme disease prevalence and density of Ixodes
      scapularis (Acari: Ixodidae) in a residential area of Dutchess County, New York.
AB  - The effects of bird feeders on local densities of Ixodes scapularis ticks and
      prevalence of Lyme disease were examined in residential areas of Dutchess County,
      NY. Ticks were collected, counted, and analyzed for Borrelia burgdorferi
      spirochetes in 2001-2002 on residential properties with and without bird feeders.
      Tick densities and infection prevalence were not significantly different on
      properties with and without bird feeders. Furthermore, analysis of a
      questionnaire, administered to 580 local residents in 2001, showed that bird
      feeders were not associated with the prevalence of Lyme disease. These
      observations suggest that bird feeders should not be considered a risk factor for
      Lyme disease in this residential setting.

PMID- 14680125
TI  - St. Louis encephalitis virus in wild birds during the 1990 south Florida
      epidemic: the importance of drought, wetting conditions, and the emergence of
      Culex nigripalpus (Diptera: Culicidae) to arboviral amplification and
      transmission.
AB  - We analyzed the prevalence of hemagglutination inhibition (HI) antibodies to St.
      Louis encephalitis (SLE) virus in wild birds during the 1990 SLE epidemic in
      Indian River County. The initial presence of SLE HI antibody was associated
      significantly with modeled drought 15 wk prior, wetting conditions 1 wk prior,
      and the emergence of the Florida SLE virus vector, Culex nigripalpus, 5 wk prior.
      Our findings indicated that three factors conspired to create the 1990 epidemic:
      (1) a large population of susceptible wild birds; (2) severe springtime drought,
      which facilitated amplification of the SLE virus among the Cx. nigripalpus and a
      portion of the wild bird population; and (3) continued rainfall and wetting of
      the land surface in the summer and early fall, which sustained a large, host
      seeking Cx. nigripalpus population. The continued biting and reproductive
      activity of Cx. nigripalpus maintained epizootic transmission throughout the
      summer and early fall in Indian River County. The high level of SLE virus
      amplification resulted in spillover transmission to humans. We hypothesize that
      without the continued reproductive activity of the vector mosquito, brought about
      by excessive summer and fall wetness, the unprecedented SLE virus amplification
      and consequent transmission to humans would not have been realized in 1990.

PMID- 14680127
TI  - Carcass enrichment does not alter decay rates or arthropod community structure: a
      test of the arthropod saturation hypothesis at the anthropology research facility
      in Knoxville, Tennessee.
AB  - In a test of an arthropod saturation hypothesis, we asked if the 30-yr history of
      carcass enrichment at the Anthropology Research Facility, Knoxville TN, has
      altered carcass decay rates or community structure of sarcosaprophagous
      arthropods, compared with three local nonenriched sites. Over a 12-d period in
      1998, using pitfall traps and sweep nets, we sampled a total of 81,000
      invertebrates from freshly euthanized pigs (Sus scrofa L.) placed in these sites.
      From this number, we sorted 69,286 forensically important (sarcosaprophagous)
      arthropods. The community structure of these organisms, as measured by species
      and individuals accumulation curves, rarefaction, and nonparametric correlation,
      was comparable in all four sites in taxonomic similarity, colonization rates,
      aerial species richness, and ranked abundances of forensically important taxa on
      a per carcass basis. Measures of carcass decay rate, remaining carcass weight (%)
      and periodic weight loss, also were similar. In most cases, carcass surface
      temperatures and maggot mass temperatures were also statistically
      indistinguishable. Probability-based results and posthoc power analyses of these
      variables led us to conclude that the sarcosaprophagous arthropod community of
      the Anthropology Research Facility is representative of surrounding sites.

PMID- 14680126
TI  - Prevalence of Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) in Ixodes
      scapularis (Acari: Ixodidae) adults in New Jersey, 2000-2001.
AB  - Using polymerase chain reaction, we analyzed 529 Ixodes scapularis Say adults
      collected from 16 of New Jersey's 21 counties for the presence of Borrelia
      burgdorferi, the etiological agent of Lyme disease. Overall, 261 (49.3%) were
      positive. B. burgdorferi was detected in ticks obtained from each county and from
      53 of the 58 (93.1%) municipalities surveyed. The observed statewide prevalence
      in New Jersey is similar to those reported from other northeastern and mid
      Atlantic states.

PMID- 14680128
TI  - Geographic information systems and spatial analysis of adult Ixodes scapularis
      (Acari: Ixodidae) in the Middle Atlantic region of the U.S.A.
AB  - In the Middle Atlantic region of the U.S.A., the vector of Lyme disease, human
      granulocytic ehrlichiosis, babesiosis, and other human and veterinary pathogens
      is the black-legged tick, Ixodes scapularis Say. In 1997 and 1998, 663 adult I.
      scapularis ticks were collected from 320 transects spanning 66,400 km2 in five
      states of the Middle Atlantic region. Tick abundance patterns were clustered,
      with relatively high numbers along the coastal plain of the Chesapeake Bay,
      decreasing to the west and south. There were significant associations between
      tick abundance and land cover, distance to water, distance to forest edge,
      elevation, and soil type.

PMID- 14680129
TI  - Culicoides mohave (Diptera: Ceratopogonidae): new occurrence records and
      potential role in transmission of hemorrhagic disease.
AB  - Biting midges of the genus Culicoides are important in the transmission of viral
      diseases affecting wild and domestic ungulates, including bluetongue (BLU) and
      epizootic hemorrhagic disease (EHD). The primary known vector for these viruses
      is C. sonorensis Wirth & Jones, however, it has been speculated that other
      species of Culicoides may also be involved. One potential candidate is C. mohave,
      a poorly studied species found in inland desert areas of the southwestern United
      States. In 2000 and 2001, we collected C. mohave and C. sonorensis at six sites
      in a previously unsurveyed area in the Sonoran Desert of southwestern Arizona and
      used PCR to detect nucleic acids associated with BLU and EHD viruses. C. mohave
      was abundant at two low-elevation sites on the study area, but uncommon or absent
      elsewhere. C. sonorensis commonly occurred along with C. mohave at one site, but
      was much less abundant. All C. mohave pools were negative for BLU viral RNA,
      however, 35% yielded positive results for EHD. All C. sonorensis were negative
      for both BLU and EHD. Our results suggest that C. mohave is a potential vector of
      EHD virus in this area, however additional studies are needed to determine its
      ability to transmit EHD.

PMID- 14680131
TI  - Body louse remains found in textiles excavated at Masada, Israel.
AB  - A leg of the body louse, Pediculus humanus humanus L. (Phthiraptera:
      Pediculidae), was found in a storeroom at Masada build during the reign of King
      Herod the Great. The unearthed culture material clearly indicates that the room
      was occupied by the rebels during the first Jewish revolt against the Romans (AD
      66-73/4). The context of the textiles associated with the louse and their nature
      suggest a rebel origin. An exuvium of a leg of the third nymphal stage of body
      louse was found. The first three parts of the leg (tarsus, including the tarsal
      claw, tibia and femur) were preserved entirely, while the fourth segment of the
      leg, the trochanter, was only partially conserved. The comparison of the tarsus
      of this specimen with the legs of present day third instar nymphs of body and
      head lice revealed that the leg found within the archaeological debris belongs to
      a body louse.

PMID- 14680130
TI  - Isolation of Japanese encephalitis and Getah viruses from mosquitoes (Diptera:
      Culicidae) collected near Camp Greaves, Gyonggi Province, Republic of Korea,
      2000.
AB  - As part of an evaluation of the ecology of arthropod-borne diseases in the
      Republic of Korea (ROK), we examined 8,765 mosquitoes captured in Paju County,
      Gyonggi Province, ROK, for the presence of viruses. Mosquitoes were captured in
      propane lantern/human-baited Shannon traps, Mosquito Magnet traps, or American
      Biophysics Corporation (East Greenwich, RI) miniature light traps with or without
      supplemental octenol bait and/or dry ice. Mosquitoes were identified to species,
      placed in pools of up to 40 mosquitoes each, and tested on Vero cells for the
      presence of virus. A total of 15 virus isolations were made from 293 pools of
      mosquitoes. Viruses were identified by reverse transcriptase-polymerase chain
      reaction and sequencing and consisted of 14 isolations of Japanese encephalitis
      (JE) virus and one isolation of Getah (GET) virus. All JE isolates were from
      Culex tritaeniorhynchus Giles, and the isolate of GET was from Aedes vexans
      (Meigen). The minimum field infection rate for JE in Cx. tritaeniorhynchus was
      3.3 per 1,000, whereas the GET virus infection rate for Ae. vexans was 0.2 per
      1,000. Isolation of JE and GET indicated that both viruses were actively
      circulating in northern Gyonggi Province, ROK. The lack of human cases of JE
      among the Korean population probably is because of an effective government
      mandated vaccination program. The reason for no cases among >10,000 United States
      military and others that reside or train nearby is unknown, but may be related to
      personnel protection measures (permethrin-impregnated uniforms and use of deet
      repellent), adult mosquito control, mosquito selection of nonhuman hosts
      (unpublished data), and the low symptomatic to asymptomatic ratio of disease in
      adults.

PMID- 14680132
TI  - A simple parafilm M-based method for blood-feeding Aedes aegypti and Aedes
      albopictus (Diptera: Culicidae).
AB  - A simple device for blood-feeding Aedes (Stegomyia) mosquitoes is described.
      Parafilm M is stretched and pressed into fiberglass window screen to form a
      packet for holding warmed blood. The method has been used successfully to
      maintain Aedes albopictus colonies for >2 yr. In typical blood-feeding trials, 53
      +/- 0.8% (+/-SE) of Aedes aegypti (Linnaeus) and 31 +/- 6% of Ae. albopictus
      (Skuse) fed to repletion.

PMID- 14680133
TI  - DNA evidence of Borrelia lonestari in Amblyomma americanum (Acari: Ixodidae) in
      southeast Missouri.
AB  - Amblyomma americanum collected near Lake Wappapello, Missouri, tested positive
      for Borrelia lonestari using polymerase chain reaction and sequence analyses of
      B. lonestari 16S rRNA and flagellin (flaB) genes. Twelve pools containing a total
      of 214 nymph or adult ticks contained evidence of infection with B. lonestari
      (minimum prevalence 5.6%). These data suggest that persons in southeast Missouri
      are at risk for exposure to B. lonestari after A. americanum tick bite, a
      possible cause of erythema migrans-like rash illness in this region. Derivation
      of the complete coding sequence for B. lonestari flaB is also reported.

PMID- 14680134
TI  - Generic and specific synonymy of Mitonyssoides stercoralis Yunker, Lukoschus, and
      Giesen, 1990 with Coprolactistus whitakeri Radovsky and Krantz, 1998 (Acari:
      Mesostigmata: Macronyssidae).
AB  - Mitonyssoides stercoralis Yunker, Lukoschus, and Giesen, 1990 is recognized as a
      senior subjective synonym of Coprolactistus whitakeri Radovsky and Krantz, 1998,
      new synonymy, and therefore Mitonyssoides Yunker, Lukoschus, and Giesen, 1990 is
      a senior synonym of Coprolactistus Radovsky and Krantz, 1998, new synonymy. By
      the species synonymy reported in this work, the known range of bat guano
      associations for M. stercoralis is extended to include both Vespertilionidae and
      Molossidae. Systematic and distributional implications of the synonymies are
      discussed.

PMID- 14680135
TI  - Adaptive significance of circadian clocks.
AB  - Circadian clocks are ubiquitous and are found in organisms ranging from bacteria
      to mammals. This ubiquity of occurrence implies adaptive significance, but to
      date there has been no rigorous empirical evidence to support this. It is
      believed that an organism possessing circadian clocks gains fitness advantage in
      two ways: (i) by synchronizing its behavioral and physiological processes to
      cyclic environmental factors (extrinsic adaptive value); (ii) by coordinating its
      internal metabolic processes (intrinsic adaptive value). There is preliminary
      circumstantial evidence to support both. Several studies using organisms living
      in constant environments have shown that these organisms possess functional
      circadian clocks, suggesting that circadian clocks may have some intrinsic
      adaptive value. Studies to assess the adaptive value of circadian clocks in
      periodic environments suggest that organisms may have a fitness advantage in
      those periodic environments, which closely match their own intrinsic periodicity.
      Furthermore, evidence from organisms living in the wild, selection studies, and
      studies on latitudinal clines suggest that circadian clocks may have an extrinsic
      adaptive value as well. In this paper, I have presented several hypotheses for
      the emergence of circadian clocks and have reviewed some major empirical studies
      suggesting adaptive significance of circadian clocks.

PMID- 14680137
TI  - Lifetimes of mRNAs for clock-regulated proteins in a dinoflagellate.
AB  - Both pulsed and continuous applications of the RNA polymerase II inhibitor
      thiolutin cause a dramatic but reversible loss of bioluminescence and its overt
      rhythmicity in cells of the dinoflagellate Lingulodinium polyedrum (formerly
      Gonyaulax polyedra). Such cells remain alive, and the rhythm resumes after an
      interval, the length of which depends on the concentration of thiolutin used. The
      period and phase of the resumed rhythm were not systematically altered following
      such treatments, and the effects were not different at different circadian
      phases. For three different genes, luciferin binding protein (lbp), luciferase
      (lcf), and glyceraldehyde-3-phosphate dehydrogenase (gapdh), which are circadian
      regulated at the level of translation, the amounts of their mRNAs were determined
      by Northern blots for times up to 12.5 h following the addition of 1.5 microM
      thiolutin. Consistent with previous reports that their abundances do not change
      with circadian time, their levels remained high for several hours after thiolutin
      addition, but then did diminish.

PMID- 14680136
TI  - Circadian rhythms, oxidative stress, and antioxidative defense mechanisms.
AB  - Endogenous circadian and exogenously driven daily rhythms of antioxidative enzyme
      activities and of low molecular weight antioxidants (LMWAs) are described in
      various phylogenetically distant organisms. Substantial amplitudes are detected
      in several cases, suggesting the significance of rhythmicity in avoiding
      excessive oxidative stress. Mammalian and/or avian glutathione peroxidase and, as
      a consequence, glutathione reductase activities follow the rhythm of melatonin.
      Another hint for an involvement of melatonin in the control of redox processes is
      seen in its high-affinity binding to cytosolic quinone reductase 2, previously
      believed to be a melatonin receptor. Although antioxidative protection by
      pharmacological doses of melatonin is repeatedly reported, explanations of these
      findings are still insufficient and their physiological and chronobiological
      relevance is not yet settled. Recent data indicate a role of melatonin in the
      avoidance of mitochondrial radical formation, a function which may prevail over
      direct scavenging. Rhythmic changes in oxidative damage of protein and lipid
      molecules are also reported. Enhanced oxidative protein modification accompanied
      by a marked increase in the circadian amplitude of this parameter is detected in
      the Drosophila mutant rosy, which is deficient in the LMWA urate. Preliminary
      evidence for the significance of circadian rhythmicity in diminishing oxidative
      stress comes from clock mutants. In Drosophila, moderately enhanced protein
      damage is described for the arrhythmic and melatonin null mutant per0, but even
      more elevated, periodic damage is found in the short-period mutant per(s),
      synchronized to LD 12:12. Remarkably large increases in oxidative protein damage,
      along with impairment of tissue integrity and--obviously insufficient-
      compensatory elevations in protective enzymes are observed in a particularly
      vulnerable organ, the Harderian gland, of another short-period mutant tau, in the
      Syrian hamster. Mice deficient in the per2 gene homolog are reported to be cancer
      prone, a finding which might also relate to oxidative stress. In the
      dinoflagellate Lingulodinium polyedrum [Gonyaulax polyedra], various treatments
      that cause oxidative stress result in strong suppressions of melatonin and its
      metabolite 5-methoxytryptamine (5-MT) and to secondary effects on overt
      rhythmicity. The glow maximum, depending on the presence of elevated 5-MT at the
      end of subjective night, decreases in a dose-dependent manner already under
      moderate, non-lethal oxidative stress, but is restored by replenishing melatonin.
      Therefore, a general effect of oxidative stress may consist in declines of easily
      oxidizable signaling molecules such as melatonin, and this can have consequences
      on the circadian intraorganismal organization and expression of overt rhythms.
      Recent findings on a redox-sensitive input into the core oscillator via
      modulation of NPAS2/BMAL1 or CLK/BMAL1 heterodimer binding to DNA indicate a
      direct influence of cellular redox balance, including oxidative stress, on the
      circadian clock.

PMID- 14680138
TI  - Entrainment of eclosion rhythm in Drosophila melanogaster populations reared for
      more than 700 generations in constant light environment.
AB  - In this paper, we report the results of our extensive study on eclosion rhythm of
      four independent populations of Drosophila melanogaster that were reared in
      constant light (LL) environment of the laboratory for more than 700 generations.
      The eclosion rhythm of these flies was assayed under LL, constant darkness (DD)
      and three periodic light-dark (LD) cycles (T20, T24, and T28). The percentage of
      vials from each population that exhibited circadian rhythm of eclosion in DD and
      in LL (intensity of approximately 100 lux) was about 90% and 18%, respectively.
      The mean free-running period (tau) of eclosion rhythm in DD was 22.85 +/- 0.87 h
      (mean +/- SD). Eclosion rhythm of these flies entrained to all the three periodic
      LD cycles, and the phase relationship (psi) of the peak of eclosion with respect
      to "lights-on" of the LD cycle was significantly different in the three periodic
      light regimes (T20, T24, and T28). The results thus clearly demonstrate that
      these flies have preserved the ability to exhibit circadian rhythm of eclosion
      and the ability to entrain to a wide range of periodic LD cycles even after being
      in an aperiodic environment for several hundred generations. This suggests that
      circadian clocks may have intrinsic adaptive value accrued perhaps from
      coordinating internal metabolic cycles in constant conditions, and that the
      entrainment mechanisms of circadian clocks are possibly an integral part of the
      clockwork.

PMID- 14680139
TI  - Impaired masking responses to light in melanopsin-knockout mice.
AB  - There are two ways in which an animal can confine its behavior to a nocturnal or
      diurnal niche. One is to synchronize an endogenous clock that in turn controls
      the sleep-wake cycle. The other is to respond directly to illumination with
      changes in activity. In mice, high illumination levels suppress locomotion
      (negative masking) and low illumination levels enhance locomotion (positive
      masking). To investigate the role of the newly discovered opsin-like protein
      melanopsin in masking, we used 1 h and 3 h pulses of light given in the night,
      and also a 3.5:3.5 h light-dark (LD) cycle. Mice lacking the melanopsin gene had
      normal enhancement of locomotion in the presence of dim lights but an impaired
      suppression of locomotion in the presence of bright light. This impairment was
      evident only with lights in the order of 10 lux or brighter. This suggests that
      melanopsin in retinal ganglion cells is involved in masking, as it is in pupil
      contraction and phase shifts. Melanopsin is especially important in maintaining
      masking responses over long periods.

PMID- 14680140
TI  - Entrainment to light of circadian activity rhythms in tench (Tinca tinca).
AB  - The present article analyzes locomotor activity rhythms in Tinca tinca. To that
      end, three different experiments were conducted on 24 animals (20 g body weight)
      kept in pairs in 60-liter aquaria fitted with infrared sensors connected to a
      computer to continuously record fish movements. The first experiment was designed
      to study the endogenous circadian clock under free-running conditions [ultradian
      40:40 min LD pulses and constant dark (DD)] and after shifting the LD cycle. Our
      results demonstrate that tench has a strictly nocturnal activity pattern, an
      endogenous rhythm being evident in 45.8% of the fish analyzed. The second
      experiment was conducted to test the influence of different photoperiods (LD
      6:18, 12:12, 18:6, and 22:2) on locomotor activity, the results showing that even
      under an extremely long photoperiod, tench activity is restricted to dark hours.
      The third experiment examined the effect of light intensity on locomotor activity
      rhythms. When fish were exposed to decreasing light intensities (from 300:0 lux
      to 30:0, 3:0, and 0.3:0 lux) while maintaining a constant photoperiod (LD 12:12),
      the highest percentage of locomotor activity was in all cases associated with the
      hours of complete darkness (0 lux). In short, our results clearly show that (a)
      tench is a species with a strictly nocturnal behavior, and (b) daily activity
      rhythms gradually entrain after shifting the LD cycle and persist under free
      running conditions, pointing to their circadian nature. However, light strongly
      influences activity rhythms, since (c) the length of the active phase is directly
      controlled by the photophase, and (d) strictly nocturnal behavior persists even
      under very dim light conditions (0.3 lux). The above findings deepen our
      knowledge of tench behavior, which may help to optimize the aquacultural
      management of this species, for example, by adjusting feeding strategies to their
      nocturnal behavior.

PMID- 14680141
TI  - Vigilance levels during and after bright light exposure in the first half of the
      night.
AB  - Fourteen healthy subjects (8 women, 6 men, aged 22-35 yr) were recruited. Each
      subject was exposed, in a counterbalanced order, to bright white light (BWL: 3000
      lux) and to dim red light (DRL: <15 lux) at a 1-week interval. Light treatments
      were administered from 00:30 to 04:30 h during sleep deprivation. Salivary
      melatonin and urinary cortisol concentrations were measured as was core body
      temperature. Vigilance levels were evaluated by subjective estimates, maintenance
      of wakefulness tests (MWT), waking EEG recordings, and three performance tests.
      Under BWL melatonin secretion was suppressed and core body temperature was
      significantly higher than under DRL. The BWL and DRL conditions produced no
      difference in cortisol secretion. Significant effects of BWL treatment were found
      for the MWT and theta-alpha and beta-1 frequency bands of the waking EEG. There
      was no significant effect of BWL on subjective alertness and performance.
      Vigilance measures were similar under the two conditions for the tests performed
      1.5 h after the end of light treatments. Overall, the findings suggest that
      bright light (BL) exposure in the first half of the night decreases EEG-defined
      sleep propensity but has only modest effects on other aspects of vigilance.

PMID- 14680142
TI  - The use of actimetry to assess changes to the rest-activity cycle.
AB  - The endogenous circadian oscillator (the body clock) is slow to adjust to altered
      rest-activity patterns. As a result, several negative consequences arise during
      night work and after time-zone transitions. The process of adjustment can be
      assessed by measurements of the sleep electroencephalogram (EEG), core
      temperature or melatonin secretion, for example, but these techniques are very
      difficult to apply in field studies, and make very great demands upon both
      experimenters and subjects. We have sought to establish if the activity record,
      measured conveniently and unobtrusively by a monitor attached to the wrist, can
      be treated in ways that enable estimates to be made of the disruption caused by
      changes to the rest-activity cycle, and the process of adjustment to them. In
      Part A, we describe the calculation and assessment of a series of "activity
      indices" that measure the overall activity pattern, activity when out of bed or
      in bed, or the activity in the hours adjacent to going to bed or getting up. The
      value of the indices was assessed by measuring changes to them in subjects
      undergoing night work or undergoing time-zone transitions. In both cases, there
      is a large body of literature describing the changes that would be expected.
      First, night workers (working 2 to 4 successive night shifts) were investigated
      during rest days and night shifts. The indices indicated that night work was
      associated with lower activity when the subjects were out of bed and higher
      activity when in bed. Some indices also measured when subjects took an afternoon
      nap before starting a series of night shifts and gave information about the
      process of adjustment to night work and recovery from it. Second, in studies from
      travelers crossing six or more time zones to the east or west, the indices
      indicated that there were changes to the rest-activity cycle immediately after
      the flights, both in its overall profile and when activity of the subjects in bed
      or out of bed was considered, and that adjustment took place on subsequent days.
      By focusing on those indices describing the activity records during the last hour
      in bed (LHIB) and the first hour out of bed (FHOB), some evidence was found for
      incomplete adjustment of the body clock, and for differences between westward and
      eastward flights. In Part B, the battery of indices are applied to the activity
      records of long-haul pilots, whose activity patterns showed a mixture of effects
      due to night work and time-zone transitions. Actimetry was performed during the
      flights themselves and during the layover days (which were either rest or work
      days). The indices indicated that all pilots had disrupted rest-activity cycles
      caused by night flights, and that there were added problems for those who had
      also undergone time-zone transitions. Rest days were valuable for normalizing the
      activity profile. For those pilots who flew to the west, adjustment was by delay,
      though not all aspects of the rest-activity cycle adjusted immediately; for those
      who flew to the east, some attempted to advance their rest-activity cycle while
      others maintained home-based activity profiles. The indices indicated that the
      activity profile was disrupted more in those pilots who attempted to advance
      their rest-activity cycle. We conclude that objective estimates of the disruption
      caused to the rest-activity cycle and the circadian system can be obtained by
      suitable analysis of the activity record.

PMID- 14680143
TI  - The relationship between assessments of jet lag and some of its symptoms.
AB  - The power of the symptoms of jet lag in predicting the amount of jet lag measured
      at the same and different times of the day has been investigated. A total of 85
      subjects was studied for 6 days after a flight from the UK to Australia (10 time
      zones to the east). At 08:00, 12:00, 16:00, 20:00, and 24:00 h, the subjects
      recorded their jet lag and fatigue. At 08:00 h, they also assessed their sleep.
      At 12:00 and 16:00 h, they assessed their attitude to a meal, as well as their
      motivation, commitment, and irritability. On retiring, they recorded bowel
      activity. Assessments were by visual analog scales. Jet lag was treated as the
      dependent variable and the symptoms as covariates in ANCOVAs. Fatigue was a
      powerful predictor of jet lag, provided it was measured at the same time, and
      some aspects of sleep predicted jet lag measured on retiring or rising. The other
      symptoms predicted jet lag less powerfully and/or at a wider range of times. It
      is concluded that, even though jet lag at any time of the day can be predicted
      from contemporaneous assessments of fatigue and that it can be predicted on
      retiring or rising from some aspects of changed sleep, jet lag is predicted less
      reliably from other symptoms, including aspects of mental performance. These
      findings question exactly what causes jet lag at a particular time of day, and so
      are relevant to studies which use this measurement to investigate the problems
      associated with time-zone transitions, and ways to ameliorate them.

PMID- 14680144
TI  - Measurement of, and some reasons for, differences in eating habits between night
      and day workers.
AB  - A questionnaire was designed to assess the following: why working people chose to
      eat or not to eat at a particular time of day; the factors that influenced the
      type of food eaten; and subjective responses to the meal (hunger before,
      enjoyment during, satiety afterward). Self-assessments were done every 3 h during
      a typical week containing work and rest days, by one group of 50 day workers and
      another group of 43 night workers. During the night work hours compared to rest
      days, night workers evidenced a significantly altered food intake, with a greater
      frequency of cold rather than hot food (p < 0.001). The type and frequency of
      meals were influenced significantly more (p < 0.05) by habit and time
      availability and less by appetite. This pattern continued into the hours
      immediately after the night shift had ended. In day workers food intake during
      work hours, compared to rest days, was also influenced significantly more often
      (p < 0.05) by time availability than hunger, but less so than with night workers.
      Moreover, day workers were less dependent than night workers upon snacks (p =
      0.01), and any significant differences from rest days did not continue beyond
      work hours. Not only did night workers change their eating habits during work
      days more than did day workers but also they looked forward to their meals
      significantly less (p < 0.001) and felt more bloated after consuming them (p <
      0.05), such effects being present to some extent during their rest days also.
      These findings have clear implications for measures designed to ease eating
      problems that are commonly problematic in night workers.

PMID- 14680145
TI  - Temporal pattern in consumption of the first drink of the day in alcohol
      dependent persons.
AB  - Loss of control over drinking and the craving for alcohol are cardinal signs of
      alcohol dependence. Our clinical practice indicates that these cravings do not
      occur randomly during the day, but at the same times each day for the same
      patient. To validate this hypothesis that alcohol-dependent patients have a
      circadian rhythmic craving in their desire for their first drink of the day, we
      asked 217 persons diagnosed as alcohol-dependent according to DSM-IV criteria to
      complete a questionnaire that surveyed whether this craving occurred at a fixed
      time each day. Of the respondents, 82% reported it did; 87% of them could state
      the time of day they consumed their first daily drink; and 80% reported that the
      time of their first drink of the day did not vary much from one day to the next.
      The most frequent time of consuming the first drink of alcohol was between 09:00
      and 11:00 h, and it was independent of the subjects' sleep-wake routine (the
      delay between the hours of wake-up and the time of the first urge for alcohol was
      3:45 +/- 3:30 h) and lunch or dinner time. This rhythmicity seems to be a
      pertinent criterion for alcohol dependence syndrome.

PMID- 14680146
TI  - Circadian rhythms in toxic effects of the serotonin antagonist ondansetron in
      mice.
AB  - The aim of the study was to learn whether the lethal and the motor incoordination
      (ataxia) side effect of ondansetron (Zophren) administration is dosing-time
      dependent. Ondansetron is a serotonin 5-HT3 receptor antagonist used primarily to
      control nausea and vomiting arising from cytotoxic chemo- and radiotherapy. A
      total of 210 male Swiss mice 10 to 12 weeks of age were synchronized for 3 weeks
      by 12 h light (rest span)/12 h dark (activity span). Different doses of
      ondansetron were injected intraperitoneally (i.p.) at fixed times during the day
      to determine both the sublethal (TD50) and lethal (LD50) doses, which were,
      respectively, 3.7 +/- 0.6 mg/kg and 4.6 +/- 0.5 mg/kg. In the chronotoxicologic
      study a single dose of ondansetron (3.5 mg/kg, i.p.) was administered to
      different and comparable groups of animals at four different circadian stages [1,
      7, 13, and 19 h after light onset (HALO)]. The lethal toxicity was statistically
      significantly dosing time-dependent (chi2 = 21.51, p < 0.0001). Drug dosing at 1
      HALO resulted in 100% survival rate whereas drug dosing at 19 HALO was only one
      half that (52%). Similarly, lowest and highest ataxia occurred when ondansetron
      was injected at 1 and 19 HALO, respectively (chi2 = 22.24, p < 0.0001). Effects
      on rectal temperature were also dosing-time related (Cosinor analysis, p <
      0.0001). The characteristics of the waveform describing the temporal patterns
      differed between the studied variables, e.g., lethal toxicity and survival rate
      showing two peaks and rectal temperature showing one peak in the 24 h time series
      waveform pattern. Cosinor analysis also revealed a statistically significant
      ultradian (tau = 8 h) rhythmic component in the considered variables. Differences
      in curve patterns in toxicity elicited by ondansetron on a per end point basis
      are hypothesized to represent the phase relations between the identified 24 h and
      8 h periodicities.

PMID- 14680148
TI  - Highlights and abstracts of the fifteenth annual Society for Light Treatment and
      Biological Rhythms virtual meeting 2003.

PMID- 14680147
TI  - PRC bisection tests.
AB  - This communication presents a new method for evaluating phase response curves
      (PRCs). A PRC describes the phase shifts produced in an oscillator by stimuli
      applied at different initial phase-states of that oscillator. In the PRC
      bisection tests, we repeatedly cut in half the circular distribution of the
      initial phase-states of the oscillator when stimuli are given. Empirically, we
      locate that optimal diameter which best bisects the circular distribution of
      phase responses into arcs of relative phase advance and phase delay. We compute a
      D score reflecting the success of the best bisection. The null hypothesis of a
      random distribution of phase responses by initial phase is tested with a Monte
      Carlo procedure, which computes Dr scores from random combinations of phase
      shifts with initial phases, thus determining the probability, given the null
      hypothesis, that the observed D score was from a random distribution. The
      bisection procedure can be extended to examine whether stronger phase shifts are
      produced in one phase response curve than in contrasting curves. Also, the
      bisection procedure yields an estimate of the inflection point of the phase
      response curve. A method is given to estimate the power of the PRC bisection
      test.

PMID- 14680149
TI  - When staff meet Staph--MRSA in the hospital setting.
AB  - Occupational health nurses are in a position to counsel and educate health care
      personnel and to work as active partners with infection control teams. A basic
      understanding and awareness of MRSA can help reduce unnecessary costs to
      institutions, unnecessary loss of time, and hopefully, help decrease the rate of
      MRSA in hospital settings.

PMID- 14680150
TI  - Designing effective interventions for small businesses.
AB  - This study effectively demonstrated the usefulness of using multiple
      interventions to achieve worker health and safety. In particular, it illustrates
      the importance of including engineering and administrative controls in
      comprehensive programs. Similarly, its use of multiple evaluation techniques,
      such as self reports of workers, workplace observations, and measurements of
      toxins increases the reliability of the findings from program evaluations. Last,
      it demonstrated the importance of including workers at every level of the
      organization in the development and implementation of the interventions.

PMID- 14680151
TI  - Electronic mail communication--management strategies.
AB  - Electronic communication has come a long way in the past 30 years. It will no
      doubt continue to improve and remain the primary communication vehicle for
      businesses. Occupational health nurses, like other business professionals, must
      use email to their advantage to improve their practice. However, electronic mail
      communication must be managed in the same manner as records and documents
      produced in any form or media.

PMID- 14680152
TI  - Websites of interest in occupational health and safety.

PMID- 14680153
TI  - The nursing shortage: an update for occupational health nurses.
AB  - Nursing is about to realize the worst shortage in history at the same time the
      first baby boomers are increasing the need for health care. A large component of
      the current and projected nursing shortage is the aging of the RN work force.
      Several factors contribute to the aging of the work force, including overall
      decline in nursing as a chosen profession, the increasing age of nursing
      graduates, and the aging of the existing RN work force. Job dissatisfaction has
      been a key issue contributing to the crisis related to recruitment and retention
      of nurses. Inadequate staffing, heavy workloads, flat salaries, and increased use
      of mandatory overtime are primary issues related to job dissatisfaction. Job
      dissatisfaction issues are key components of retention of nursing personnel.
      Occupational health nurses are experts in dealing with issues of ergonomic
      challenges, workplace violence, mandatory overtime, stress related injuries, and
      high stress associated with nursing.

PMID- 14680154
TI  - Occupational health nurses' educational needs: what do they want?
AB  - Educational preferences, impediments to obtaining an education, and the needs of
      occupational health nurses are not well understood. The purposes of this regional
      study were to determine the graduate and continuing educational preferences,
      impediments, and needs of occupational health nurses in the states of Texas, New
      Mexico, Arkansas, Louisiana, and Oklahoma. Questionnaires (1,172) were mailed to
      all occupational health nurses identified by the respective state boards of
      nursing (N = 5). Results from 256 (response rate of 21.8%) returned
      questionnaires show 43.8% were interested in obtaining a graduate degree in
      occupational health nursing while only 48.8% of employers encourage them to
      obtain a higher degree. Only 33.2% reported the company for which they work
      provides rewards for obtaining an advanced degree or certification as an
      occupational health nurse. The two greatest impediments to obtaining a graduate
      degree as an occupational health nurse were a long distance from campus (56.3%)
      and lack of money (37.9%).

PMID- 14680155
TI  - Identification and management of vascular risk: beyond low density lipoprotein
      cholesterol.
AB  - Vascular disease is basically an inherited metabolic disease. Eighty percent of
      individuals who develop disease have the same blood cholesterol levels as
      individuals who do not develop disease. With vascular disease pervasive
      throughout the world and current assessment techniques insufficient to identify
      those at risk, use of a multifactorial approach to vascular assessment is
      prudent. Assays are currently available that enable health care providers to
      determine risk beyond those traditionally used. These "novel" risk factors appear
      to be additive (Brown, 2001; Rader, 2000a, 2002; Superko, 1995), and when
      combined with traditional factors, LDL can be adjusted to prevent disease. In
      individuals with established disease, these factors can be instrumental in
      identifying an appropriate treatment protocol for halting the progression of
      disease. To date, the health care establishment as a whole has done a poor job of
      identifying and thoroughly treating cardiovascular risk. Even when risks were
      identified, often treatment protocols have not been aggressive enough to reach
      targeted goals (Hoerger, 1998; Jacobson, 2000; NHANES III, 2000). The unique role
      of the occupational health nurse offers an opportunity to follow a client during
      long periods of time. This is useful in establishing trust and getting to know
      the specific problems of each individual. The occupational health nurse,
      therefore, stands at the threshold of change for the client, easing and assisting
      the client to reach individual goals. This group of nurses can play a significant
      role in forging prevention and stamping out the number one killer of the American
      population.

PMID- 14680156
TI  - Over the counter medications--use caution!

PMID- 14680157
TI  - Observation of the orbital angular momentum spectrum of a light beam.
AB  - We demonstrate an experimental scheme that allows the elucidation of the orbital
      angular momentum discrete spectrum of an arbitrary light signal. The orbital
      angular momentum spectrum is represented in a Laguerre-Gaussian mode base, and
      the spectral components are resolved in the frequency domain by exploiting the
      Doppler frequency shift that is imparted to rotating light beams.

PMID- 14680158
TI  - Measurement of optical trapping forces by use of the two-photon-excited
      fluorescence of microspheres.
AB  - A novel technique for the calibration of laser trapping systems that utilizes two
      photon-excited fluorescence of commercial dye-stained microspheres has been
      demonstrated. The trapping forces as well as the trapping efficiency have been
      measured for various liquid environments and trapping depths. The trapping
      efficiency in water was found to decrease with an increase of trapping depths
      because of the enlargement of the trapping beam waist caused by aberrations of
      the optical system.

PMID- 14680159
TI  - Reference-wave solutions for the high-frequency fields in inhomogeneous
      background random media.
AB  - Ray theory plays an important role in determining the propagation properties of
      high-frequency fields and their statistical measures in complicated random
      environments. For computations of the statistical measures it is therefore
      desirable to have a solution for the high-frequency field propagating along an
      isolated ray trajectory. A new reference wave is applied to obtain an analytic
      solution of the parabolic wave equation that describes propagation along the ray
      trajectory of the deterministic-background medium. The methodology is based on
      defining a paired-field measure as a product of an unknown field propagating in a
      disturbed medium and the complex-conjugate component propagating in a medium
      without random fluctuations. When a solution of the equation for the paired-field
      measure is obtained, the solution of the deterministic component can be extracted
      from the paired solution to determine the solution of the unknown field in an
      explicit form.

PMID- 14680160
TI  - Gain-flattened fiber Raman amplifiers with nonlinearity-broadened pumps.
AB  - Gain flattening of an E-band (1360-1460-nm) fiber Raman amplifier was achieved by
      pump spectral broadening to a 16.3-nm linewidth by use of nonlinearity in a 6.2
      km standard fiber. With the broadened pump, the characteristic Raman gain ripple
      was removed and the 3-dB gain bandwidth was increased by 10.6 nm relative to the
      nonbroadened pump case. The experimental results agreed well with a gain profile
      simulation. The use of a 100-m holey fiber for pump broadening was also
      investigated near 1.56 microm for U-band (1625-1675-nm) Raman amplifiers. Much
      less broadening was observed, which is believed to be a result of less four-wave
      mixing.

PMID- 14680161
TI  - Evanescent-wave infrared spectroscopy with flattened fibers as sensing elements.
AB  - Fiber-optic evanescent-wave spectroscopy (FEWS) is a novel method for measuring
      the absorption spectra of samples in contact with a segment of an optical fiber
      that serves as a sensing element. We used a cylindrical IR-transmitting AgClBr
      fiber whose central section, of length L, was flattened to a thickness d. This
      section was used as the FEWS sensing element. Our theoretical work predicted that
      the signals obtained in FEWS measurements should be linearly dependent on L and
      inversely proportional to d. Decreasing the thickness can significantly increase
      its sensitivity of the sensor. These theoretical results were verified
      experimentally by measurements of methanol and water.

PMID- 14680162
TI  - Analysis of intrachannel four-wave mixing in differential phase-shift keying
      transmission with large dispersion.
AB  - Intrachannel four-wave mixing (IFWM) in highly dispersed differential phase-shift
      keying (DPSK) transmission systems is studied with a simple analytical model and
      numerical simulation. It is found that the IFWM effect in DPSK systems is smaller
      and less dependent on the bit pattern than in on-off-keying systems with the same
      average power. The reduced pulse energy in DPSK and correlation between the
      nonlinear phase shifts of two adjacent pulses contribute to the robustness of
      DPSK versus IFWM.

PMID- 14680163
TI  - Effect of cross-phase-modulation-induced polarization scattering on optical
      polarization mode dispersion compensation in wavelength-division-multiplexed
      systems.
AB  - Interchannel cross-phase-modulation-induced polarization scattering (XPMIPS) and
      its effect on the performance of optical polarization mode dispersion (PMD)
      compensation in wavelength-division-multiplexed (WDM) systems are studied. The
      level of XPMIPS in long-haul WDM transmission systems is theoretically
      quantified, and its effect on optical PMD compensation is evaluated with
      numerical simulations. We show that in 10-Gbit/s ultra-long-haul dense WDM
      systems XPMIPS could reduce the PMD compensation efficiency by 50%, whereas for
      40-Gbit/s systems the effect of XPMIPS is smaller.

PMID- 14680164
TI  - Stress-induced birefringence in microstructured optical fibers.
AB  - We present a numerical study of stress-induced birefringence in microstructured
      optical fibers (MOFs), using a finite-element method. MOFs under lateral forces
      and twists are considered separately. Compared with that in standard single-mode
      optical fibers, stress-induced linear birefringence in MOFs under a lateral force
      is reduced with increasing air-hole size, whereas twist-induced circular
      birefringence in MOFs is enhanced when the air-hole size is small.

PMID- 14680165
TI  - Mode-field radius of photonic crystal fibers expressed by the V parameter.
AB  - We numerically calculate the equivalent mode-field radius of the fundamental mode
      in a photonic crystal fiber (PCF) and show that this is a function of the V
      parameter only and not the relative hole size. This dependence is similar to what
      is found for graded-index standard fibers, and we furthermore show that the
      relation for the PCF can be excellently approximated with the same general
      mathematical expression. This is to our knowledge the first semianalytical
      description of the mode-field radius of a PCF.

PMID- 14680166
TI  - Blind deconvolution under band limitation.
AB  - A blind deconvolution problem is newly stated with the following conditions: the
      point-spread function is band limited, both the object and the point-spread
      function are nonnegative, and the solution is to be a diffraction-limited object.
      A blind deconvolution method was developed that can easily be applied to problems
      in optics because of the conditions used. The performance of the method is
      investigated with computer simulations.

PMID- 14680167
TI  - Depth-resolved multiphoton polarization microscopy by third-harmonic generation.
AB  - We achieve depth-resolved polarization microscopy by measuring third-harmonic
      generation induced by a tightly focused circularly polarized beam. In crystals
      exhibiting strong birefringence this signal is dominated by positively phase
      matched third-harmonic generation. This process occurs in only optically
      anisotropic media, in which the birefringence compensates for the phase mismatch
      between the fundamental and the third harmonic induced by dispersion. Both the
      intensity and the polarization of the emitted signal provide information on the
      local optical anisotropy. We demonstrate the technique by imaging biogenic
      crystals in sea urchin larval spicules.

PMID- 14680168
TI  - Using diffractograms to evaluate optical systems with coherent illumination.
AB  - A new approach to measuring aberrations of an optical system with coherent
      illumination is introduced. The optical system is evaluated by use of a so-called
      weak phase object and by digital image recording and processing. Based on the
      contrast transfer function theory for coherent systems, the main aberrations of
      the optical system can be determined. This is a convenient approach to evaluating
      and measuring complex optical systems with numerous optical elements after
      assembly and can serve as a simple performance test of an optical instrument in
      the field.

PMID- 14680170
TI  - Absolute frequency measurement of an acetylene-stabilized laser at 1542 nm.
AB  - The absolute frequency of an acetylene-stabilized laser at 1542 nm is measured at
      its second harmonic (771 nm) by use of a femtosecond optical comb based on a mode
      locked Ti:sapphire laser. Frequency stability and reproducibility of the
      acetylene-stabilized laser are evaluated by the femtosecond comb with a H maser
      as a frequency reference. The absolute frequency of a laser diode stabilized on
      the P(16) transition of 13C2H2 is determined to be 194 369 569 383.6(1.3) kHz.
      The acetylene-stabilized laser serves as an important optical frequency standard
      for telecommunication applications.

PMID- 14680169
TI  - Three-dimensional spectrally encoded imaging.
AB  - A method for three-dimensional surface measurements with phase-sensitive
      spectrally encoded imaging is demonstrated. Both transverse and depth information
      is transmitted through a single-mode optical fiber, allowing this scheme to be
      incorporated into a miniature probe. This approach is demonstrated by measurement
      of the profile of a lens surface and by three-dimensional imaging of the face of
      a small doll.

PMID- 14680171
TI  - Thermal stresses in optical waveguides.
AB  - Birefringence of optical waveguides is closely related to the anisotropy of
      thermal stresses in the core. Closed-form solutions for estimating the thermal
      stresses in the cladding layers and in the core of an embedded channel waveguide
      are presented. The solutions are verified by finite-element simulation. It is
      found that the thermal stress in the core in the direction perpendicular to the
      wafer cannot be ignored, and one can tune the core stress anisotropy in the plane
      normal to the light-propagation direction by varying the thermal-expansion
      mismatch between the upper cladding and the substrate.

PMID- 14680172
TI  - Improvement of passive Q-switching performance reached with a new Nd-doped mixed
      vanadate crystal Nd:Gd0.64Y0.36VO4.
AB  - Passive Q-switching performance was found to be greatly improved by use of a new
      Nd-doped mixed vanadate crystal Nd:Gd0.64Y0.36VO4 compared with that achieved
      with Nd:YVO4 and Nd:GdVO4. At an absorbed pump power of 12 W, an average output
      power of 2.78 W was obtained at a pulse repetition frequency of 15.4 kHz with an
      optical conversion efficiency of 23.2%, and the slope efficiency was determined
      to be 45.5%. The resulting pulse energy, peak power, and pulse width were 181
      microJ, 26.6 kW, and 6.8 ns, respectively.

PMID- 14680173
TI  - Efficient laser performance of Nd:GdVO4 crystals grown by the floating zone
      method.
AB  - Efficient laser performance is demonstrated with Nd:GdVO4 crystals grown by the
      floating zone method. With a 2-at. % Nd-doped crystal a slope efficiency of 67%
      is achieved with pumping at 808 nm. We also find that pumping at 879 nm with a
      bandwidth of 1.8 nm is practical for laser diode pumping. With this pumping level
      the slope efficiency reaches 78%. High-quality Nd:GdVO4 crystals are successfully
      grown with as much as 15-at.% Nd concentration by the floating zone method
      without inclusions or macroscopic defects. Homogeneity and high reproducibility
      of crystal growth are confirmed.

PMID- 14680174
TI  - Resonance transition 795-nm rubidium laser.
AB  - Population inversion of the 2P 1/2 and 2S 1/2 levels and continuous-wave, three
      level laser oscillation at 795 nm on the D1 transition of the rubidium atom has
      been demonstrated. Using a titanium sapphire laser as a pump source, we obtained
      a slope power efficiency of 54% relative to absorbed pump power, consistent with
      homogeneous broadening of the rubidium pump and laser transitions. The end-pumped
      rubidium laser performance was well described by use of literature spectroscopic
      and kinetic data in a model that takes into account ground-level depletion and a
      pump spectral bandwidth that is substantially larger than the collisionally
      broadened pump transition spectral width.

PMID- 14680175
TI  - Uniqueness and wavelength optimization in continuous-wave multispectral diffuse
      optical tomography.
AB  - We derive conditions for the unique and simultaneous recovery of chromophore
      concentrations and scattering coefficients in multispectral continuous-wave
      diffuse optical tomography. These conditions depend strongly on measurement
      wavelengths. We introduce and demonstrate a general methodology for choosing
      those wavelengths, which yields superior separation of scattering from absorption
      and superior separation of one chromophore from another. Application of these
      concepts should significantly improve the fidelity of continuous-wave diffuse
      near-infrared optical tomography in tissues.

PMID- 14680176
TI  - Color generation in butterfly wings and fabrication of such structures.
AB  - The wings of the morpho butterfly demonstrate an iridescent blue color over wide
      viewing angles. The mechanism that generates this blue color is studied. Optical
      and transmission electron microscopy of the butterfly wings reveal a complex wing
      structure with as many as 24 layers with periodic structures. The color
      generation is caused by interference of the multilayer structure as well as
      diffraction. It is possible to specially design grating structures so that a
      specific blue color can be generated and observed over wider angles. To
      demonstrate the grating concept, complex multigratings are designed and
      fabricated with electron-beam lithography. The light-diffraction properties of
      these gratings are presented.

PMID- 14680177
TI  - Generation and stability of discrete gap solitons.
AB  - We analyze stability and generation of discrete gap solitons in weakly coupled
      optical waveguides. We demonstrate how both stable and unstable solitons can be
      observed experimentally in the engineered binary waveguide arrays and also reveal
      a connection between the gap-soliton instabilities and limitations on the mutual
      beam focusing in periodic photonic structures.

PMID- 14680178
TI  - Soliton emission at a phase-mismatch boundary in a quadratic nonlinear film
      waveguide.
AB  - We report the experimental demonstration of spatial nonlinear beam displacement
      caused by an interface between periodically modulated and uniform quadratic
      nonlinearity. We observe intensity- and phase-mismatch-dependent spatial beam
      displacement at 1548 nm in lithium niobate waveguides. The device has the
      potential to provide a soliton-emission-based, ultrafast all-optical switch.

PMID- 14680179
TI  - Spatially localized states with size-dependent optical bistability.
AB  - Experimental results of a new type of localized state generated in an optical
      system consisting of a liquid-crystal spatial light modulator with optical
      feedback are demonstrated. The localized state is triggered at a position that
      depends on the size of a control beam because its formation depends on the
      fraction of high-spatial-frequency components in the feedback light that passes
      through a low-cut spatial-frequency filter. This novel size-dependent switching
      property is useful for erasing individual target localized states.

PMID- 14680180
TI  - Time-resolved measurements of self-focusing pulses in air.
AB  - The spatial, spectral, and temporal properties of self-focusing 798-nm 100-fs
      pulses in air are experimentally measured with high-resolution, single-shot
      techniques at a set propagation distance of 10.91 m. The data, obtained with an
      initially collimated Gaussian beam, show significant evolution of spatial
      narrowing as well as temporal and spectral changes at intensities lower than
      those required for significant ionization of air.

PMID- 14680181
TI  - Reorientational optical nonlinearity of nematic liquid-crystal cells near the
      nematic-isotropic phase transition temperature.
AB  - We address the reorientational optical nonlinearity of homogeneously aligned
      neamtic liquid-crystal (NLC) cells. The propagation of light in NLC cells depend
      strongly on temperature. At a temperature approaching the clearing point, an
      undulating beam and multifocal points are observed in the NLC cell by use of a
      polarizing optical microscope. Using a conoscopic technique, we observed novel
      consecutive concentric and parabolic patterns projected onto a screen. Optical
      energy is considered to compete with thermal energy to affect NLC's orientation
      and to generate singularities in the steady state. A model of the configuration
      of the liquid crystal's orientation is proposed.

PMID- 14680182
TI  - Characterization of a supercontinuum generated from a photonic crystal fiber and
      its application to coherent Raman spectroscopy.
AB  - The temporal and spectral profiles of supercontinuum radiation generated from a
      photonic crystal fiber are evaluated with a polarization-gate frequency-resolved
      optical gating technique. The supercontinuum is then applied to coherent inverse
      Raman spectroscopy. A stimulated Raman signal of cyclohexane is observed as an
      induced absorption signal with an instantaneous response. The Raman signal has a
      peak at a slight negative delay time, which is explained by perturbed Raman
      induced coherence.

PMID- 14680183
TI  - Modulational instability and space-time dynamics in nonlinear parabolic-index
      optical fibers.
AB  - Beam propagation in multimode graded-index parabolic optical fibers in the
      presence of group-velocity dispersion and Kerr nonlinearity is theoretically
      investigated. It is shown that a modulational instability arising from the
      periodic spatial focusing of the beam takes place regardless of the sign of fiber
      dispersion, leading to a highly nonlinear space-time dynamics and the generation
      of ultrashort optical pulses.

PMID- 14680184
TI  - Highly efficient 1063-nm continuous-wave laser emission in Nd:GdVO4.
AB  - Highly efficient 1-microm continuous-wave laser emission in 3-mm-thick, 0.5- and
      1.0-at. % Nd:GdVO4 crystals longitudinally pumped at 879 nm into the laser
      emitting level is reported. Under Ti:sapphire pumping, the slope efficiency in
      absorbed power is approximately 80% for both crystals, while the slope
      efficiency, the optical-to-optical efficiency (at 1700-mW pump power), and the
      laser threshold in incident power are 79%, 78%, and 31 mW for 0.5-at. % Nd and
      80%, 77%, and 40 mW for 1.0-at. % Nd, respectively. The slope efficiency is close
      to the quantum defect limit, the difference being fully accounted for by the
      residual optical losses. Under 879-nm diode laser pumping, the slope efficiency
      and the optical-to-optical efficiency in absorbed power of the 0.5-at. % Nd:GdVO4
      crystal are 60% and 53%, owing to poorer superposition of the pumped and the
      laser mode volumes.

PMID- 14680185
TI  - Optical two-beam coupling for a surface-induced photorefractive effect in undoped
      liquid crystals.
AB  - We report beam-coupling measurements of undoped nematic planar cells, for which
      the surface-induced photorefractive effect (SIPRE) has been confirmed to be due
      to photoelectric interface activation. We show that the energy transfer strongly
      depends on experimental geometry. Diffraction efficiency and beam-coupling
      analyses suggest that the unusual local and (or) nonlocal behavior can be
      ascribed to an additional in-phase-modulated longitudinal electric field
      component, unaccountable by standard photorefractivity. We consider a simple
      charge distribution model of the SIPRE, which produces a space-charge field
      having two orthogonal modulated components, in phase and pi/2 out of phase.
      Through the liquid crystal's electric response, the exploited geometries verify
      the presence of the two components.

PMID- 14680186
TI  - All-optical neural-net-like image processing with photosensitive nonlinear
      nematic film.
AB  - Received June 30, 2003 We demonstrate that some neural-net image-processing
      operations can be realized in an all-optical manner by use of the natural
      diffraction property of light in conjunction with the photosensitivity and
      optical nonlinearities of a transparent thin film. An example of image edge
      enhancement is illustrated with photosensitive supranonlinear nematic liquid
      crystal films.

PMID- 14680187
TI  - Evanescent polarization holographic recording of sub-200-nm gratings in an
      azobenzene polyester.
AB  - I demonstrate high-resolution polarization holographic recording with evanescent
      waves in a thin film of an azobenzene polyester deposited directly on the
      hypotenuse of a highly refractive prism. A spatial frequency greater than 7000
      lines/mm and diffraction efficiency greater than 1% have been achieved. It was
      found that diffraction efficiency increases in the dark after the writing beams
      have been switched off. The biphotonic effect found in other azobenzene polymers,
      which converts cis states of the azobenzene to trans states followed by an
      ordering process that is due to aggregation, is proposed as the reason for this
      increase in diffraction efficiency.

PMID- 14680188
TI  - Low-loss polymeric optical waveguides with large cores fabricated by hot
      embossing.
AB  - A simple low-cost method of fabricating polymeric optical waveguides with large
      core sizes for plastic optical fibers is presented. The waveguides are fabricated
      by hot embossing with an ultraviolet-cured epoxy resin stamper. The stamper is
      fabricated by replication of a rectangular groove mold that is made from silicone
      rubber replicated from a ridged original silicon master. The master is fabricated
      by anisotropic etching of (110) single-crystal silicon. Optical waveguides with
      large core sizes of 100-500 microm have been fabricated, and a low propagation
      loss of 0.19 dB/cm at 650 nm was achieved.

PMID- 14680189
TI  - Parallel microgenetic algorithm design for photonic crystal and waveguide
      structures.
AB  - We have developed a powerful parallel genetic algorithm design tool for photonic
      crystal and waveguide structures. The tool employs a small-population-size
      genetic algorithm (microgenetic algorithm) for global optimization and a two
      dimensional finite-difference time-domain method to rigorously design and
      optimize the performance of photonic devices. We discuss the implementation and
      performance of this design tool. We demonstrate its application to two photonic
      devices, a defect taper coupler to connect conventional waveguides and photonic
      crystal waveguides, and a sharp 90 degrees waveguide bend for low index contrast
      waveguides.

PMID- 14680190
TI  - Ultracompact high-efficiency polarizing beam splitter with a hybrid photonic
      crystal and conventional waveguide structure.
AB  - We propose an ultracompact high-efficiency polarizing beam splitter that operates
      over a wide wavelength range and is based on a hybrid photonic crystal and a
      conventional waveguide structure. Within a small area (15 microm x 10 microm),
      this polarizing beam splitter separates TM- and TE-polarized modes into
      orthogonal output waveguides. Results of simulations with the two-dimensional
      finite-difference time-domain method show that 99.3% of TM-polarized light is
      deflected by the photonic crystal structure (with a 28.0-dB extinction ratio),
      whereas 99.0% of TE-polarized light propagates through the structure (with a 32.2
      dB extinction ratio). Wave vector diagrams are employed to explain the operation
      of a polarizing beam splitter. Tolerance analysis reveals a large tolerance to
      fabrication errors.

PMID- 14680191
TI  - Fiber-assisted detection with photon number resolution.
AB  - We report the development of a photon-number-resolving detector based on a fiber
      optical setup and a pair of standard avalanche photodiodes. The detector is
      capable of resolving individual photon numbers and operates on the well-known
      principle by which a single-mode input state is split into a large number (eight)
      of output modes. We reconstruct the photon statistics of weak coherent input
      light from experimental data and show that there is a high probability of
      inferring the input photon number from a measurement of the number of detection
      events on a single run.

PMID- 14680192
TI  - Enhancement of spontaneous emission from the resonant modes of a photonic crystal
      slab single-defect cavity.
AB  - Modification of the spontaneous-emission lifetime in photonic crystal single
      defect resonant modes is studied with the finite-difference time domain method.
      We investigate spontaneous-emission enhancement from the monopole and the dipole
      modes of a hexagonal lattice cavity, considering the effects of the finite
      emitter linewidth and spectral detuning. Large spontaneous-emission enhancement
      of > 50 is achieved numerically from the high-quality-factor monopole mode when
      the emitter linewidth is comparable with the resonant-mode linewidth. However, if
      broad-linewidth material is used and a detuning effect is included, the dipole
      mode with a low quality factor and a smaller mode volume could be more
      advantageous for spontaneous-emission enhancement.

PMID- 14680193
TI  - Ponderomotive shearing for spectral interferometry of extreme-ultraviolet pulses.
AB  - We propose a novel method for completely characterizing ultrashort pulses at
      extreme-ultraviolet (XUV) wavelengths by adapting the technique of spectral phase
      interferometry for direct electric-field reconstruction to this spectral region.
      Two-electron wave packets are coherently produced by photoionizing atoms with two
      time-delayed replicas of the XUV pulse. For one of the XUV pulses,
      photoionization occurs in the presence of a strong infrared pulse that
      ponderomotively shifts the binding energy, thereby providing the spectral shear
      needed for reconstruction of the spectral phase of the XUV pulse.

PMID- 14680194
TI  - Pulse picking by phase-coherent additive pulse generation in an external cavity.
AB  - We have implemented a simple method for generating an "amplified" phase-coherent
      light pulse in which a pulse train of phase-coherent, equidistant input light
      pulses from a mode-locked Ti:sapphire laser is coupled into a ring cavity
      resonator whose length is matched to the mode-locked pulse repetition frequency
      at 82 MHz. Pulses are thus coherently superimposed and added inside the buildup
      cavity and form an intense pulse that is switched out from the cavity via a fast
      acousto-optic modulator. The method thus provides a pulse train at a reduced and
      controlled repetition frequency and with higher pulse energies than the original
      mode-locked pulses.

PMID- 14680195
TI  - Ultrashort-pulse wave-front autocorrelation.
AB  - Combined spatially resolved collinear autocorrelation and Shack-Hartmann wave
      front sensing of femtosecond laser pulses is demonstrated for the first time to
      our knowledge. The beam is divided into multiple nondiffracting subbeams by thin
      film micro-optical arrays. With hybrid refractive-reflective silica/silver
      microaxicons, wave-front autocorrelation is performed in oblique-angle
      reflection. Simultaneous two-dimensional detection of local temporal structure
      and wave-front tilt of propagating few-cycle wave packets is demonstrated.

PMID- 14680196
TI  - Two-color chirped-pulse amplification in an ultrabroadband Ti:sapphire ring
      regenerative amplifier.
AB  - We have developed a high-energy, ultrabroadband Ti:sapphire ring regenerative
      amplifier capable of producing in excess of 20-mJ output at a 10-Hz repetition
      rate. The technique of chirped-pulse amplification is used to generate two-color,
      time-synchronized pulses with central wavelength separations of up to
      approximately 120 nm and with a total energy of 10 mJ by use of a regenerative
      pulse-shaping technique. Mid-infrared pulses tunable from 6 to 11 microm are
      generated by difference frequency mixing the two-color outputs.

PMID- 14680197
TI  - Orthogonal control of the frequency comb dynamics of a mode-locked laser diode.
AB  - We have performed detailed studies on the dynamics of a frequency comb produced
      by a mode-locked laser diode (MLLD). Orthogonal control of the pulse repetition
      rate and the pulse-to-pulse carrier-envelope phase slippage is achieved by
      appropriate combinations of the respective error signals to actuate the diode
      injection current and the saturable absorber bias voltage. Phase coherence is
      established between the MLLD at 1550 nm and a 775-nm mode-locked Ti:sapphire
      laser working as part of an optical atomic clock.

PMID- 14680198
TI  - Automated spatiotemporal diffraction of ultrashort laser pulses.
AB  - We exploit the close similarities between time-frequency and position-wave-vector
      correspondences to control the spatiotemporal diffraction pattern of ultrashort
      laser pulses. This approach permits novel, automated generation of sophisticated
      two-dimensional femtosecond waveforms. A two-dimensional space-time version of a
      Gerchberg-Saxton algorithm is used to iteratively determine the phase pattern in
      position-frequency space that produces a user-defined intensity profile in wave
      vector-time space.

PMID- 14680199
TI  - Passively mode-locked glass waveguide laser with 14-fs timing jitter.
AB  - Ultralow jitter pulse trains are produced from a passively mode-locked,
      erbium/ytterbium co-doped, planar waveguide laser by use of high-bandwidth
      feedback control acting on the physical cavity length and optical pump power.
      Synchronization of a 750-MHz, fundamentally mode-locked laser to an external
      clock signal yields an ultralow, root-mean-square relative timing jitter of 14.4
      fs integrated from 10 Hz to the Nyquist frequency of 375 MHz.

PMID- 14680200
TI  - Molecular epidemiology of rotaviruses in India.
AB  - Rotaviruses cause an estimated 140 million cases of gastroenteritis and 800,000
      deaths in children between the ages of 6 months to 2 yr in developing countries.
      In India, one of every 250 children or about 100-150,000 children die of
      rotavirus diarrhoea each year. The prevalence of rotavirus diarrhoea in India has
      been found to vary from 5-71 per cent in hospitalized children <5 yr of age with
      acute gastroenteritis. The seasonal variation of rotavirus diarrhoea in India
      varies in different geographical regions with high incidence in winter months at
      low relative humidity in north India. The distinctive features of rotavirus
      infection in India include the occurrence of severe disease at an early age and
      common neonatal rotavirus infections which are often asymptomatic. Rotavirus
      shows genetic and antigenic diversity in terms of subgroup, electropherotypes and
      G and P serotypes/genotypes. There are a few studies in terms of prevalence of
      different antigenic and genetic variants from various regions of India. In most
      studies on subgroup distribution from India a higher prevalence of subgroup II
      was reported compared to subgroup I. Electropherotyping has also demonstrated
      that a number of multiple electropherotypes co-circulate at one time in a
      particular community leading to extensive genomic variation and the appearance of
      new strains which may become the predominant electropherotype during the peak
      season. The most common G types reported from India are G1 and G2 and P types are
      P[4] and P[8]. A significant number of children also have mixed rotavirus
      infections. G9 strains are also quite commonly seen in Indian children. In
      addition P6 strains of probable bovine origin have been reported from India. A
      novel neonatal strain P type 11 human rotavirus (116 E) was isolated from
      neonates in Delhi, the VP4 of which was closely related to the bovine serotype
      G10P[11] strain B223 and VP7 was closely related to the human serotype G9 strain.
      Another neonatal strain G10P[11] was reported from Bangalore. G10P[11] strains
      also have a high prevalence in calves with diarrhoea, in India. The occurrence of
      these unusual rotavirus strains which are natural reassortants of human and
      bovine rotaviruses, suggests that reassortment may be an important mechanism for
      generation of rotavirus strains of newborns. This is catalyzed by the age old
      traditions of calves and humans living in the same household and socio-economic
      conditions in India. The diversity of rotavirus strains and the high prevalence
      of mixed infections in India are unique features of rotavirus epidemiology in
      India and emphasizes that vaccines should be formulated against a broad range of
      strains. Another important aspect is that vaccines in India should also target G9
      strains. Since neonates acquiring rotavirus infection are protected against
      severe diarrhoea, neonatal rotavirus strains can be effective potential vaccine
      candidates and vaccines based on these neonatal strains are being indigenously
      developed in India.

PMID- 14680201
TI  - Indirect immunofluorescent antibody test for the rapid diagnosis of melioidosis.
AB  - Culture is the only reliable method available at present for the diagnosis of
      melioidosis. Though serological tests have been described, their value in routine
      diagnosis is controversial. All indirect immunofluorescent assay (IFA) was
      therefore evaluated to determine its use in the diagnosis of melioidosis. Whole
      cell antigen prepared from a laboratory isolate of Burkholderia pseudomallei was
      used to assay IgG and IgM antibodies. Fourteen of the 22 (63.6%) culture proven
      cases had IgM antibodies while only 10 (45.5%) had IgG antibodies. Negative
      predictive value of IgM assay was 92 per cent. Positive predictive value was 100
      per cent if both IgM and IgG were considered together. The present study done on
      a limited number of samples suggests that IFA may be useful in routine diagnosis
      of melioidosis.

PMID- 14680202
TI  - Therapeutic efficacy of anti-malarials in Plasmodium falciparum malaria in an
      Indo-Myanmar border area of Arunachal Pradesh.
AB  - BACKGROUND & OBJECTIVES: Malaria is one of the major public health problems in
      the north eastern region of India. Antimalarial drug resistance is widespread and
      one of the important causes of recent resurgence of falciparum malaria in this
      region. Antimalarial drugs are seen to be used sequentially one after another in
      many areas of the region, when therapeutic failure is observed with a drug. In
      view of this, the present study was undertaken to assess the therapeutic efficacy
      of common antimalarial drugs viz., chloroquine, sulfadoxine+pyrimethamine (S-P)
      and quinine, administered sequentially to the patients with Plasmodium falciparum
      infection in a Myanmar bordering area of Arunachal Pradesh. METHODS: A hospital
      based in vivo study was carried out with 53 patients with uncomplicated
      falciparum malaria. All patients were first treated with chloroquine and
      therapeutic efficacy assessed. In case of therapeutic failure of chloroquine
      combination drug (S-P) was given and those showing failure with S-P combination,
      oral quinine was administered and followed up for 28 days to assess both clinical
      and parasitological responses. RESULTS: Therapeutic failure was observed with
      chloroquine in 83.1 per cent (44 of 53) and to both chloroquine and S-P
      combination drug in 44.1 per cent (19/43) patients. Further, 15.8 per cent
      patients (3 of 19) failed to respond even to quinine. Overall, 5.7 per cent
      patients (3 of 53) showed unresponsiveness to all the three drugs i.e.,
      chloroquine, S-P combination and quinine. Asexual parasite clearance and also
      fever clearance was slowest with chloroquine and fastest with quinine.
      INTERPRETATION & CONCLUSION: The findings of this study show the presence of
      multi drug failure P. falciparum in Jairampur-Nampong, a western Myanmar
      bordering area of Arunachal Pradesh. Anti malarial drug resistance is increasing
      in Indo-Myanmar border areas and systematic studies need to be done to review the
      situation.

PMID- 14680203
TI  - Association of deletion in the chromosomal 8p21.3-23 region with the development
      of invasive head & neck squamous cell carcinoma in Indian patients.
AB  - BACKGROUND & OBJECTIVES: Deletions in chromosome 8 (chr.8) have been shown to be
      necessary for the development of head and neck squamous cell carcinoma (HNSCC).
      Attempts have been made in this study to detect the minimal deleted region in
      chr.8 associated with the development of HNSCC in Indian patients and to study
      the association of clinicopathological features with the progression of the
      disease. METHODS: The deletion mapping of chr.8 was done in samples from 10
      primary dysplastic lesions and 43 invasive squamous cell carcinomas from the head
      and neck region of Indian patients to detect allelic alterations (deletion or
      size alteration) using 12 highly polymorphic microsatellite markers. The
      association of the highly deleted region was correlated with the tumour node
      metastasis (TNM) stages, nodal involvement, tobacco habit and human papilloma
      virus (HPV) infection of the samples. RESULTS: High frequency (49%) of loss of
      heterozygosity (LOH) was seen within 13.12 megabase (Mb) region of chromosomal
      8p21.3-23 region in the HNSCC samples, whereas the dysplastic samples did not
      show any allelic alterations in this region. The highest frequency (17%) of
      microsatellite size alterations (MA) was observed in the chr.8p22 region. The
      loss of short arm or normal copy of chr.8 and rare bi-allelic alterations were
      seen in the stage II-IV tumours (939, 5184, 2772, 1319 and 598) irrespective of
      their primary sites. The highly deleted region did not show any significant
      association with any of the clinical parameters. However, HPV infection was
      significantly associated (P < 0.05) with the differentiation grades and overall
      allelic alterations (LOH/MA) of the samples. INTERPRETATION & CONCLUSION: Our
      data indicate that the 13.12 Mb deleted region in the chromosomal 8p21.3-23
      region could harbour candidate tumour suppressor gene(s) (TSGs) associated with
      the progression anti invasion of HNSCC tumours in Indian patients.

PMID- 14680204
TI  - Tranexamic acid in paediatric cardiac surgery.
AB  - BACKGROUND & OBJECTIVES: Antifibrinolytic agents are used commonly in adult
      cardiac surgery to reduce postoperative blood loss. Paucity of literature on the
      use of a newer antifibrinolytic agent tranexamic acid (TA) in children undergoing
      cardiac surgery promoted us to conduct this study in children with cyanotic heart
      disease. METHODS: One hundred and twenty consecutive children with cyanotic heart
      disease were randomised into two groups. Control (group A) (n=24) given no drug
      while the study (group B, n=96) group was given tranexamic acid 10 mg/kg each
      after anaesthetic induction, on bypass and after protamine at the end of bypass.
      Postoperatively, total mediastinal chest tube drainage and blood and blood
      product usage at 24 h were recorded. Tests of coagulation including activated
      clotting time, fibrinogen, fibrin degradation products and platelet count were
      performed at 6 h postoperatively. RESULTS: The two groups were comparable in
      terms of demographic characteristics such as age, sex, weight, operations
      performed, and preoperative haematocrit. Postoperatively, group B, had a
      significantly (P<0.05) lower blood loss, blood and blood product usage, re
      exploration rate compared to the control group. There was preservation of
      fibrinogen and lower levels of fibrin degradation products in group B.
      INTERPRETATION & CONCLUSION: Tranexamine acid was highly effective in reducing
      post-operative blood loss, blood and blood product usage in children with
      congenital cyanotic heart disease undergoing corrective surgery.

PMID- 14680205
TI  - Formaldehyde inhalation & open field behaviour in rats.
AB  - BACKGROUND & OBJECTIVES: It has been shown in animal studies that repeated
      exposure to formaldehyde vapour alters behaviour and memory. Since information is
      not available on the behavioural consequences of acute formaldehyde exposure,
      this study was conducted to investigate the influence of single inhalative
      exposure to formaldehyde on the explorative and locomotor behaviour of adult male
      and female rats. METHODS: Rats were exposed to different concentrations of
      formaldehyde vapour (0.5, 1.0, 2.5%, corresponding to inhalation chamber
      concentrations of 1.0, 2.5, and 5.0 ppm, respectively) for 2 h and an open field
      test was carried out 2 h after the end of exposure (first test) and repeated 24 h
      thereafter (second test). The parameters examined were crossing of floor squares,
      sniffing, grooming, rearing, climbing, and defaecation. RESULTS: In exposed male
      rats, significant reduction of crossed floor squares, grooming, and wall
      climbing, and increase in floor sniffing and rearing were observed in the first
      test. During the second test, males in the groups exposed to 2.5 ppm and 5 ppm
      crossed significantly higher numbers of squares when compared to controls. Air
      sniffing, wall climbing, and rearing were altered in all exposed males. Control
      males showed higher incidence of defaecation in comparison to the values of first
      test. The formaldehyde-exposed female rats crossed significantly decreased
      numbers of floor squares in the first test. In females in the 2.5 ppm and 5 ppm
      groups, decreased grooming and enhanced floor sniffing were observed. In the
      second test, all exposed females crossed higher numbers of floor squares than
      controls. Frequencies of air and floor sniffing were higher in females exposed to
      2.5 ppm and lower in those exposed to 1 ppm. Defaecation was enhanced in females
      in the 2.5 ppm group in comparison to the first test. INTERPRETATION &
      CONCLUSION: The results show that formaldehyde inhalation in the concentrations
      and duration of exposure used in the present experiments significantly influences
      the locomotor and explorative behaviour of rats after a single exposure in a
      gender-related manner and that various behavioural components in the exposed
      animals remains altered even after 24 h.

PMID- 14680206
TI  - Enzymatic hydrogen atom abstraction from polyunsaturated fatty acids.
AB  - The oxidation of polyunsaturated fatty acids such as arachidonic and linoleic
      acid initiates a plethora of cell signaling pathways in animals and plants. The
      chemistry of the enzymatic oxidation has been investigated for several enzymes,
      most notably prostaglandin synthase and the lipoxygenases, revealing many
      surprises and impressive examples of enzymatic control of hydrogen atom
      abstraction and subsequent oxygenation.

PMID- 14680207
TI  - The aromatic sidechains of amino acids as neutral donor groups for alkali metal
      cations.
AB  - An aromatic residue that can serve as a pi-donor occurs in all known protein
      sequences about one out of every 11 amino acids. Benzene, phenol, and indole, the
      sidechains of phenylalanine, tyrosine, and tryptophan, are particularly important
      in protein structure. Solid state structures confirm the interactions of these
      neutral arenes, along with double and triple bonds, with sodium and potassium
      cations.

PMID- 14680208
TI  - A metallosupramolecular tetrahedron with a huge internal cavity.
AB  - A huge molecular tetrahedral complex forms quantitatively by self-assembly from
      four ligands L-H6 and four titanium(IV) ions; in the solid state it encapsulates
      four [K(DIMF)3]+ units in its interior.

PMID- 14680209
TI  - Novel alignment technique for LCD-biosensors.
AB  - The directional drying of a low-salt Tris-EDTA (TE)-buffer to give an alignment
      layer offers a simple, one-step, non-contact procedure for the construction of
      parallel liquid crystal displays (LCDs), which can be used to amplify the
      presence of DNA to scales visible to the naked eye, opening up possibilities for
      easy detection of bio recognition events.

PMID- 14680210
TI  - Photoinduced Ba2+ release and thermal rebinding by an azacrown ether linked by an
      alkynyl pyridine to a (bpy)Re(CO)3 group.
AB  - A novel complex in which an azacrown ether is linked by an alkynyl pyridine to a
      (bpy)Re(CO)3 group acts as a light-controlled ion switch: Ba2+ bound to the
      azacrown is released in ca. 10 ns on UV excitation, and rebinds thermally from
      bulk solution in ca. 1 micros.

PMID- 14680211
TI  - A bilayer to monolayer phase transition in liquid crystal glycolipids.
AB  - Investigations of the thermotropic liquid-crystalline properties of 6,6'-di-O
      stearoylsucrose show, for the first time, that glycolipids can exhibit phase
      transitions within the smectic A phase.

PMID- 14680213
TI  - Self-assembly of a unique hexadecanuclear [4 x (2 x 2)]-Pb16 'grid of grids' type
      structure.
AB  - A new ligand containing a linear sequence of four-tridentate chelating subunits
      built around alkoxide and pyrimidine bridging groups undergoes a spontaneous self
      assembly process with Pb(CF3SO3)2 to produce a unique hexadecanuclear [4 x (2 x
      2)] 'grid of grids' type structure with external dimensions of 26 A.

PMID- 14680212
TI  - The C-terminal ester of membrane anchored peptide ion channels affects anion
      transport.
AB  - Five heptapeptide derivatives, [CH3(CH2)17]2NCOCH2OCH2CO-Gly-Gly-Gly-Pro-Gly-Gly
      Gly-OR, in which R = ethyl, 2-propyl, heptyl, benzyl, and cyclohexylmethyl, were
      found to transport chloride anion through a phospholipid bilayer to varying
      extents dependent on the identity of R. It was concluded that the R group is a
      membrane anchor for the synthetic chloride channels.

PMID- 14680214
TI  - Controlled haptotropic rearrangements--towards a stereospecific molecular switch
      based on chiral arene chromium complexes.
AB  - A stereospecific molecular switch has been designed based on a reversible thermo-
      or photo-induced haptotropic shift of a Cr(CO)3 fragment along a
      naphthohydroquinone skeleton.

PMID- 14680215
TI  - Contraction/extension molecular motion by protonation/deprotonation induced
      structural switching of pyridine derived oligoamides.
AB  - NMR, mass spectrometry and X-ray diffraction studies show reversible structural
      interconversion between helical and extended forms of pyridine derived oligoamide
      molecular strands, by simple protonation/deprotonation.

PMID- 14680216
TI  - Cell-permeable small molecule probes for site-specific labeling of proteins.
AB  - We have successfully synthesized a number of small molecule probes designed for
      site-specific labeling of N-terminal cysteine-containing proteins expressed in
      live cells. Their utility for site-specific, covalent modifications of proteins
      was successfully demonstrated with purified proteins in vitro, and with live
      bacterial cells in vivo.

PMID- 14680217
TI  - Excellent enantio-selective enclathration of (2R,3S)-3-methyl-2-pentanol in
      channel-like cavity of 3-epideoxycholic acid, interpreted by the four-location
      model for chiral recognition.
AB  - Pure (2R,3S)-3-methyl-2-pentanol is resolved from the racemates by a steroidal
      host; the interpretation of the recognition mechanism based on the crystal
      structure reveals that CH/O interaction between the host and guest plays a
      decisive role in enantio-selective enclathration of the small aliphatic secondary
      alcohol.

PMID- 14680218
TI  - Tuning molecular orientation with STM at the solid/liquid interface.
AB  - Triptycene molecular orientation has been tuned with a STM tip at a Cu(111)
      surface in solution from flat, to tilt, to vertical. The tuning is completely
      bias dependent and reversible. The study is important in the fields of
      nanoscience and technology.

PMID- 14680219
TI  - A TDDFT description of the low-energy excited states of copper and zinc
      metalloenediynes.
AB  - Time-dependent density functional theory shows that the photoreactivities of
      copper and zinc metalloenediynes derive from multi-configurational excited states
      involving the enediyne and pyridine pi systems.

PMID- 14680220
TI  - A supramolecular approach to lithium ion solvation at nanostructured dye
      sensitised inorganic/organic heterojunctions.
AB  - A novel arylamine based hole transporting material (HTM) with tetraethylene
      glycol (TEG) side groups is reported. Lithium ions solubilised by the TEG groups
      are employed to modulate interfacial electron transfer reactions at a dye
      sensitised TiO2/HTM interface.

PMID- 14680221
TI  - Highly efficient ethylene polymerisation by scandium alkyls supported by neutral
      fac-kappa3 coordinated N3 donor ligands.
AB  - Reaction of [M(CH2SiMe3)3(THF)2] (M = Sc or Y) with the neutral fac-kappa3 N3
      donor ligands (L) Me3[9]aneN3 or HC(Me2pz)3 gave the corresponding trialkyls
      [M(L)(CH2SiMe3)3]; activation of the scandium congeners with B(C6F5)3 in the
      presence of ethylene afforded highly active polymerisation catalysts (Me3[9]aneN3
      = 1,4,7-trimethyltriazacyclononane).

PMID- 14680222
TI  - Synthesis and X-ray structures of silver and gold guanidinate-like complexes. A
      Au(II) complex with a 2.47 A Au-Au distance.
AB  - The structures of the tetranuclear silver(I), [Ag4(hpp)4], and the dinuclear
      gold(II), [Au2(hpp)2Cl2], (hpp = 1,3,4,6,7,8-hexahydro-pyrimido[1,2
      a]pyrimidinate) guanidinate-like bases are reported and show a silver-silver
      distance of 2.8614(6) A and a gold-gold distance of 2.4752(9) A, the shortest Au
      Au bond heretofore reported.

PMID- 14680223
TI  - A rationally designed novel receptor for probing cooperative interaction between
      metal ions and bivalent tryptophan side chain in solution.
AB  - Cooperative interactions between metal ions and bivalent tryptophan side chain
      are identified in water by fluorescence quenching of a designed novel receptor,
      EDTA-bis(L-tryptophan methyl ester), supplemented by a circular dichroism study;
      results revealed that the receptor is capable of distinguishing a variety of
      metal ions on the basis of their abilities in quenching tryptophan fluorescence
      and the relative magnitude of these interactions is Cu2+ approximately Fe2+ >>
      Co2+ > Ni2+ >> Mn2+ > Zn2+ > La3+ > Al3+.

PMID- 14680224
TI  - On-chip separation of peptides prepared within a micro reactor.
AB  - We have demonstrated that peptides may be electrophoretically separated from
      unreacted reagents within an integrated micro reactor.

PMID- 14680225
TI  - Magnetic bead-based label-free chemiluminescence detection of telomeres.
AB  - For the first time we report on the detection of telomeres by coupling of the
      label-free guanine CL detection route with an efficient magnetic isolation of the
      hybrid.

PMID- 14680226
TI  - Manganese N-confused porphyrin reactivity: CH bond activation and meso carbon
      reduction.
AB  - Manganese N-confused porphyrins activate C-C and C-H bonds upon heating or air
      oxidation; the dimer complex [Mn(NCTPP)]2 is reduced at two meso positions, and
      the pyridine coordinated monomer breaks the internal C-H bond upon heating or
      exposure to oxygen.

PMID- 14680227
TI  - Electrophilic terminal phosphinidene complex-Lewis base adducts: chemistry
      between carbon-halide bond activation and weak Lewis base adduct formation.
AB  - Comparative studies on the reactivity of a transiently formed terminal
      phosphinidene complex towards various organobromide derivatives show that carbon
      bromine bond insertion is preferred with benzyl bromide, whereas formal HBr
      insertion resulted with 2-bromopyridine and a surprising selectivity enhancement
      (of the phosphinidene complex) was observed with bromobenzene; all new products
      were established by elemental analyses, NMR spectroscopy, mass spectrometry and
      single crystal X-ray diffraction studies.

PMID- 14680228
TI  - Efficient preparation of 1,4,8-trimethylcyclam and its conversion into a
      thioalkyl-pendant pentadentate chelate.
AB  - A facile synthesis of 1,4,8-trimethylcyclam and a thioalkyl-pendant derivative
      are reported, and the X-ray crystal structure of a nickel(II) complex illustrates
      structural consequences of appending the thiolate donor onto the macrocycle.

PMID- 14680229
TI  - Synthetic studies on ecteinascidin 743: rapid access to the fully functionalized
      tetrahydroisoquinoline with a bridged 10-membered sulfur containing macrocycle.
AB  - Synthesis of tetrahydroisoquinoline with a 1,4-bridged 10-membered sulfur
      containing macrolactone (5) is described. Phenolic aldolisation, Pictet-Spengler
      cyclisation of an acid sensitive amino diol under newly developed conditions
      (LiBr, toluene-TFE, 80 degrees C) and acid promoted intramolecular C-S bond
      formation leading to a 10-membered cycle are key steps of our synthesis.

PMID- 14680230
TI  - Paired cell for the preparation of AgI nanowires using nanoporous alumina
      membrane templates.
AB  - This communication describes a relatively new and simple method for the
      preparation of AgI nanowires using nanoporous alumina membrane templates which
      can be easily extended to prepare nanowires of many other materials.

PMID- 14680232
TI  - Unusual reactions of N-allylic difluoroenamines under thermal conditions.
AB  - N-Allylic difluoroenamines exhibited unusual behaviors under thermal conditions;
      N-allyl difluoroenamines in refluxing xylene afforded not only aza-Claisen
      rearrangement products, but also 2-azabicyclo[2.1.1]hexanes, whose formation
      could be explained via intramolecular [2+2]-cycloaddition, whilst N-prenyl
      difluoroenamine underwent an ene reaction to give the pyrrolidine as a sole
      product.

PMID- 14680231
TI  - A tyrosine-modified hypocrellin B with affinity for and photodamaging ability
      towards calf thymus DNA.
AB  - An enhanced photodamaging ability towards CT-DNA was achieved in a tyrosine
      modified hypocrellin B by improving the affinity of the sensitizer to DNA.

PMID- 14680233
TI  - Noncovalent functionalization of multi-walled carbon nanotubes by pyrene
      containing polymers.
AB  - Multi-walled carbon nanotubes (MWNTs) have been solubilized in water and in
      various organic solvents by noncovalent side-wall functionalization by pyrene
      containing polymers.

PMID- 14680234
TI  - Light-emitting charge transfer species promoted by metal ion coordination.
AB  - The coordinative interaction between zinc(II) and naphthalene-labeled
      diiminopyridine ligands induces the formation of light-emitting intracomplex
      charge transfer species.

PMID- 14680235
TI  - Photoelectrochemical decomposition of water on nanocrystalline BiVO4 film
      electrodes under visible light.
AB  - The nanocrystalline BiVO4 film electrode on conducting glass showed an excellent
      efficiency (IPCE = 29% at 420 nm) for the decomposition of water under visible
      light.

PMID- 14680236
TI  - A self-seeded, surfactant-directed hydrothermal growth of single crystalline
      lithium manganese oxide nanobelts from the commercial bulky particles.
AB  - Single crystalline lithium manganese oxide nanobelts were obtained through a self
      seeded, surfactant-directed growth process from the commercial bulky particles
      under hydrothermal treatment. A possible mechanism was proposed to explain the
      growth of the nanobelts. This new process could be extended to prepare other one
      dimensional nanomaterials such as Se nanorods, Te nanotubes, and MnO2 nanowires.

PMID- 14680237
TI  - Novel low-molecular-weight hydrogelators based on 2'-deoxyuridine.
AB  - We have synthesized low-molecular-weight, triazole ring-appended 2'-deoxyuridine
      hydrogelators that gelate pure water at a concentration as low as 0.2 wt% and
      these compounds display different aggregation and network structures as evidenced
      by their SEM images, FTIR spectra and minimum gel concentrations.

PMID- 14680238
TI  - Synthesis and properties of thiazoline based ionic liquids derived from the
      chiral pool.
AB  - A novel class of chiral ionic liquids derived from amino alcohols is prepared in
      multi-gram scale. Their potential in chiral recognition is shown in a preliminary
      example with racemic Mosher's acid salt.

PMID- 14680239
TI  - Synthesis of novel axially chiral Rh-NHC complexes derived from BINAM and
      application in the enantioselective hydrosilylation of methyl ketones.
AB  - Novel axially chiral Rh N-heterocyclic carbene complexes were prepared from
      axially dissymmetric 1,1'-binaphthalenyl-2,2'-diamine and applied in the Rh
      catalyzed enantioselective hydrosilylation of methyl ketones. The corresponding
      sec-alcohols can be obtained in high yields with good to excellent ee.

PMID- 14680240
TI  - An efficient recognition motif for an alkyl moiety in water.
AB  - The artificial receptor bearing decamethylene groups bridging the porphyrin
      framework and the hydrophilic poly(ethylene oxide) auxiliary groups showed
      incremental binding free energy of 3.5 kJ mol(-1) per CH2 for 4-alkylpyridines,
      demonstrating that an ideal hydrophobic environment for the recognition of an
      alkyl group is constructed in water.

PMID- 14680241
TI  - Quantitative analysis of multivalent interactions of carbohydrate-encapsulated
      gold nanoparticles with concanavalin A.
AB  - Multivalent interactions between carbohydrate-encapsulated gold nanoparticles and
      Con A are found with high affinity and specificity.

PMID- 14680242
TI  - The Os/Cu-Al-hydrotalcite catalysed hydroxylation of alkenes.
AB  - A new Os/Cu-Al-hydrotalcite-like catalyst is described which, with N
      methylmorpholine oxide as co-oxidant, heterogeneously catalyses the hydroxylation
      of olefins to give diols selectively and in high yield.

PMID- 14680243
TI  - Room temperature borylation of arenes and heteroarenes using stoichiometric
      amounts of pinacolborane catalyzed by iridium complexes in an inert solvent.
AB  - Aromatic C-H borylation of arenes and heteroarenes using stoichiometric amounts
      of pinacolborane was catalyzed by an iridium complex generated from
      1/2[Ir(OMe)(COD)]2 and 4,4'-di-tert-butyl-2,2'-bipyridine at room temperature in
      hexane and afforded the corresponding aryl- and heteroarylboronates in high
      yields with excellent regioselectivities.

PMID- 14680244
TI  - Enzyme-facilitated enantioselective transport of (S)-ibuprofen through a
      supported liquid membrane based on ionic liquids.
AB  - Coupling lipase reactions with a supported liquid membrane (SLM) based on ionic
      liquids showed facilitative and selective permeation of (S)-ibuprofen through the
      SLM, indicating successful optical resolution of a racemic mixture using the
      enzyme-facilitative SLM.

PMID- 14680245
TI  - Regioselective uncatalysed hydrophosphination of alkenes: a facile route to P
      alkylated phosphine derivatives.
AB  - The synthesis of alkylarylphosphines is easily carried out by hydrophosphination
      of unactivated alkenes under mild thermal activation; gram scale amounts of
      products can be prepared by this simple methodology.

PMID- 14680246
TI  - Rapid synthesis of oligosaccharides using an anomeric fluorous silyl protecting
      group.
AB  - A fluorous silyl ether tag as protecting group at the anomeric position of sugar
      acceptors allows rapid synthesis of oligosaccharides by reducing the purification
      procedures to a simple and fast fluorous solid-phase extraction.

PMID- 14680247
TI  - Noncontact two-color luminescence thermometry based on intramolecular luminophore
      cyclization within an ionic liquid.
AB  - A self-referencing optical thermometer based on a reversible, temperature
      dependent monomer-excimer interconversion of 1,3-bis(1-pyrenyl)propane dissolved
      in an ionic liquid and operating in the 25 to 140 degrees C range is reported.

PMID- 14680248
TI  - Design and synthesis of DNA-tethered ruthenium complexes that self-assemble into
      linear arrays.
AB  - Ruthenium(II) bis(terpyridine) complexes have been prepared with two triethylene
      glycol linkers to which DNA sequences have been attached; hybridization at
      various complex ratios results in linear arrays of varying lengths.

PMID- 14680249
TI  - Tethered 2 + 2 + 2 cycloaddition reactions of cobalt-cycloheptyne complexes.
AB  - Cycloheptyne-dicobalt hexacarbonyl complexes, substituted by propargylic ether
      functions, undergo 2 + 2 + 2 cycloaddition reactions with alkynes to give
      tricyclic benzocycloheptanes; an all-intramolecular version of this
      transformation is also possible.

PMID- 14680250
TI  - Thiazole orange as fluorescent universal base in peptide nucleic acids.
AB  - Thiazole orange is shown to possess characteristics of a universal base while
      maintaining duplex stability. Its fluorescence properties allowed distinction
      between matched and single mismatched hybridisation.

PMID- 14680252
TI  - Synthesis and structure of [Na11(OtBu)10(OH)]: 1H NMR shift of a hydroxide ion
      encapsulated in a 21-vertex alcoholate cage.
AB  - [Na11(OtBu)10(OH)], a hydroxide enclosing 21-vertex cage compound, was found to
      crystallize from mixtures of sodium tert.butanolate with sodium hydroxide. Its
      structure can be derived from the known (NaOtBu)6-hexaprismane by replacing one
      butanolate unit with OH- and capping the latter with five additional units of
      NaOtBu. The hydroxide shows a signal at -3.21 ppm in the 1H NMR spectrum.

PMID- 14680251
TI  - A comparison of the photochemical reactivity of N@C60 and C60: photolysis with
      disilirane.
AB  - N@C60 has a lower photochemical reactivity toward disilirane than C60, although
      N@C60 does not differ from C60 in its thermal reactivity; theoretical
      calculations reveal that N@C60 and C60 have the same orbital levels and that
      N@3C60* has a shorter lifetime than 3C60*.

PMID- 14680253
TI  - Synthesis of nearly monodisperse polystyrene-polypeptide block copolymers via
      polymerisation of N-carboxyanhydrides.
AB  - Primary amine hydrochlorides promote a well-controlled ring-opening
      polymerisation of Z-L-lysine-N-carboxyanhydride in DMF at 40-80 degrees C; the
      polystyrene-poly(Z-L-lysine) block copolymers synthesised exhibit a very narrow
      molecular weight distribution, close to a Poisson distribution.

PMID- 14680254
TI  - A novel molecular ladder structure of Cu(II)-Ba(II) coordination polymer
      exhibiting ferromagnetic coupling.
AB  - A novel one-dimensional ladder-like Cu-Ba compound ([Ba(H2O)3(CuL)2] x 2H2O)n
      (H3L = Glycylglycine, N-[1-(2-hydroxyphenyl)propylidene]), has been synthesized
      and structurally characterized; it exhibits ferromagnetic interaction.

PMID- 14680255
TI  - Blind faith?

PMID- 14680256
TI  - Changes in hospital performance after ownership conversions.
AB  - This paper examines the effects of ownership conversions on hospital performance
      between 1987 and 1998 in areas of financial performance, staffing, capacity, and
      unprofitable care. Conversions to government and for-profit ownership both
      increased the profit margin: the former due to rising revenue, and the latter due
      to reduced operating costs and rising revenue. Hospitals that converted to for
      profit ownership had the greatest reduction in staffing relative to other
      converted hospitals. There was little change in bed capacity after conversion to
      for-profit status, but some reductions in bed capacity after conversion to
      government or nonprofit status. No conversion of any kind led to a reduced amount
      of unprofitable care, but conversion to private ownership (nonprofit and for
      profit) increased the probability of trauma center closures.

PMID- 14680257
TI  - Health and the cost of nongroup insurance.
AB  - This analysis estimates a selection-adjusted model of the premium for nongroup
      insurance to measure the effect of health status on the cost of nongroup
      insurance. Using data from two recent national surveys, the probability of buying
      nongroup insurance is about 50% lower for people in fair or poor health compared
      to similar people in excellent health. Correcting for selection, premiums are
      about 15% higher for people with modest health problems, and 43% to 50% higher
      for people with major health problems compared to those in excellent health. We
      use the selection-corrected premiums to simulate the effects on the price and
      affordability of nongroup insurance for the uninsured under two recent tax credit
      proposals.

PMID- 14680258
TI  - The effect of parents' insurance coverage on access to care for low-income
      children.
AB  - This study examines the effects of having an uninsured parent on access to health
      care for low-income children. Using data from the 1999 National Survey of
      America's Families, we find that having an uninsured parent decreases the
      likelihood that a child will have any medical provider visit by 6.5 percentage
      points, and decreases the likelihood of a well-child visit by 6.7 percentage
      points. Estimates for low-income children who have insurance but have an
      uninsured parent indicate a 4.1 percentage-point reduction in the probability of
      having any medical provider visit, and a similar 4.2 percentage-point reduction
      in the probability of having a well-child visit relative to those with insured
      parents. The effects of having an uninsured parent are smaller in magnitude than
      the effects of a child being uninsured. Efforts to increase insurance coverage of
      parents, either by extending eligibility for public insurance or through other
      policy interventions, will have positive spillover effects on access to care for
      children. Although the magnitude of these effects is small relative to the direct
      effect of providing insurance to either the child or parent, they should be
      considered in analyses of costs and benefits of proposed policies.

PMID- 14680259
TI  - The impact of Medicaid primary care case management on office-based physician
      supply in Alabama and Georgia.
AB  - The success of the "primary care case management (PCCM)" form of managed care
      implemented in many state Medicaid programs over the past several years depends
      in part on the expanded availability of primary care physician sites to
      substitute for hospital-based outpatient care and to provide a medical home for
      enrollees. However, the PCCM requirement for physicians to accept assignment of a
      caseload of patients and to provide all of their primary care likely conflicts
      with the approach of limited Medicaid participation favored by many Medicaid
      physician participants. This study examines the early impact of PCCM
      implementation, in the absence of physician reimbursement level increases, on the
      patterns of Medicaid participation by physicians in communities in Georgia and
      Alabama. We find that the implementation of PCCM under these conditions often was
      associated with reductions in the proportion of physicians participating in
      Medicaid, reductions in the number of very small Medicaid practices, and declines
      in Medicaid visit volumes across all participating physicians. We also find
      evidence of an overall reduction in the number of primary care visits per
      Medicaid enrollee, but an increase in the proportion of these visits that were
      for preventive care services associated with initial PCCM implementation.

PMID- 14680260
TI  - Impact of the National Practitioner Data Bank on resolution of malpractice
      claims.
AB  - Policymakers and commentators are concerned that the National Practitioner Data
      Bank (NPDB) has influenced malpractice litigation dynamics. This study examines
      whether the introduction of the NPDB changed the outcomes, process, and equity of
      malpractice litigation. Using pre- and post-NPDB analyses, we examine rates of
      unpaid claims, trials, resolution time, physician defense costs, and payments on
      claims with a low/high probability of negligence. We find that physicians and
      their insurers have been less likely to settle claims since introduction of the
      NPDB, especially for payments less than dollars 50,000. Because this disruption
      appears to have decreased the proportion of questionable claims receiving
      compensation, the NPDB actually may have increased overall tort system
      specificity.

PMID- 14680261
TI  - Improving nurse staffing measures: discharge day measurement in "adjusted patient
      days of care".
AB  - Previous research cannot account for the discrepancy between registered nurse
      (RN) reports of understaffing and studies showing slight improvement. One reason
      may be that "adjusted patient days of care" (APDC) underestimates patient load.
      Using data from all Pennsylvania acute care general hospitals for the years 1994
      through 1997, we found that APDC is underestimated by two hours. After adjusting
      APDC, we examined the difference in nurse staffing over the period 1991-2000
      before and after the adjustment. We found a significant difference between
      unadjusted and adjusted measures. However, when applied to the changes in nurse
      staffing between 1991 and 2000, the difference was not enough to account for the
      discrepancy between reports and data. Other measurement and conceptual problems
      may exist in terms of patients' increasing acuity levels, patients' declining
      lengths of stay and the associated greater proportion of nurse time devoted to
      admission and discharge, and lack of recent data in some empirical studies.

PMID- 14680262
TI  - Hospital cost efficiency.

PMID- 14680263
TI  - A functionalized THz sensor for marker-free DNA analysis.
AB  - We report on a novel resonant THz sensor for the label-free analysis of DNA
      molecules. The sensor allows the direct detection of DNA-probe molecules at
      functionalized electrodes via hybridization. Subsequent time resolved
      photoconductive sampling of the THz transmission identifies the binding state
      between probe and target DNA. Integrating neighbouring sensors on a chip, this
      technique can be extended to a parallel analysis of multiple DNA sequences. A
      clearly readable sensor response is obtained with less then 40 fmol of 20-mer
      single-stranded DNA molecules, indicating at least a sevenfold sensitivity
      increase compared to previous approaches.

PMID- 14680264
TI  - The magnetic lead field theorem in the quasi-static approximation and its use for
      magnetoencephalography forward calculation in realistic volume conductors.
AB  - The equation for the magnetic lead field for a given magnetoencephalography (MEG)
      channel is well known for arbitrary frequencies omega but is not directly
      applicable to MEG in the quasi-static approximation. In this paper we derive an
      equation for omega = 0 starting from the very definition of the lead field
      instead of using Helmholtz's reciprocity theorems. The results are (a) the
      transpose of the conductivity times the lead field is divergence-free, and (b)
      the lead field differs from the one in any other volume conductor by a gradient
      of a scalar function. Consequently, for a piecewise homogeneous and isotropic
      volume conductor, the lead field is always tangential at the outermost surface.
      Based on this theoretical result, we formulated a simple and fast method for the
      MEG forward calculation for one shell of arbitrary shape: we correct the
      corresponding lead field for a spherical volume conductor by a superposition of
      basis functions, gradients of harmonic functions constructed here from spherical
      harmonics, with coefficients fitted to the boundary conditions. The algorithm was
      tested for a prolate spheroid of realistic shape for which the analytical
      solution is known. For high order in the expansion, we found the solutions to be
      essentially exact and for reasonable accuracies much fewer multiplications are
      needed than in typical implementations of the boundary element methods. The
      generalization to more shells is straightforward.

PMID- 14680265
TI  - Quasi-monochromatic x-rays for diagnostic radiology.
AB  - Monochromatic x-ray beams are desirable in various fields of diagnostic
      radiology; in fact a reduction of the dose and an enhancement of the contrast
      could be achieved. In this work two different methods to monochromatize x-ray
      beams produced by conventional tubes have been compared. In the first one the
      beam is obtained via Bragg diffraction on mosaic crystal and in the second one by
      attenuating the polychromatic beam with aluminium filters. We have simulated
      quasi-monochromatic x-ray spectra by setting suitable values of Bragg's angle to
      obtain beams tuned to 20, 30, 40 and 50 keV with the SHADOW code, an x-ray
      tracing program designed to study the propagation and the interaction of a photon
      beam through an optical system. We have validated such a program by comparing
      some calculated data with measurements carried out on an experimental apparatus.
      Attenuated polychromatic x-ray spectra have been simulated by setting appropriate
      values of aluminium filters and potential with the SPECTRUM PROCESSOR, the
      software version of the Catalogue of Spectral Data for Diagnostic X-Rays, which
      provides radiographic x-ray spectra that can be attenuated with several material
      filters. The relation between the energy resolution and the flux as a function of
      the mean energy has been investigated and results have been compared. Results
      show that quasi-monochromatic x-ray beams produced via Bragg diffraction exhibit,
      for a given mean energy and energy resolution, a higher total flux compared to
      attenuated spectra.

PMID- 14680266
TI  - Beam characteristics of upper and lower physical wedge systems of Varian
      accelerators.
AB  - The beam characteristics of a dual physical wedge system, upper and lower, for
      Varian accelerators are studied over the energy range 6-18 MV. Wedge factors for
      both systems are measured in a water phantom as a function of field size, depth
      and source-to-wedge (SWD) distance. Our results indicate that apart from their
      physical differences, dosimetrically, the two wedge systems have <2% difference
      in central axis percentage depth dose beyond the build-up region. The lower wedge
      central axis percentage depth dose is consistently lower than that of the
      corresponding upper wedge, with the effect more pronounced for large field sizes.
      The wedge profiles are identical within 2% for all field sizes, depths and
      energies. The wedge factors for both wedge systems are also within 2% for all
      field sizes and depths for both 6 and 15 MV photons and slightly higher for the
      18 MV beam and 45 degrees-60 degrees wedge angle. The wedge factor variation with
      SWD reveals an interesting fact that thinner wedges (15 degrees and 30 degrees)
      result in a higher surface dose in the central axis region than thicker wedges.
      As the SWD increases beyond 80 cm, the reverse is true, i.e. thicker wedges
      produce higher surface dose than thinner wedges. It is also verified that the
      wedge factor at any depth and for any field size can be calculated from the
      wedged and open field central axis percentage depth dose, and the wedge factor at
      dmax, resulting in nearly 44% reduction in water phantom scanning and 80%
      reduction in point measurements during commissioning.

PMID- 14680267
TI  - Optical properties of poly(2,6-dimethyl-1,4-phenylene oxide) film and its
      potential for a long-term solar ultraviolet dosimeter.
AB  - The optical properties of poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) film have
      been characterized in order to develop an alternative method for UV dosimetry
      with a focus on long-term human exposure measurements. The dynamic range of PPO
      film was found to extend to 2 MJ m(-2) of broadband UV exposure independently of
      film thickness, providing an exposure range of roughly four summer days at
      subtropical latitudes. The sensitivity of the film to UV exposure was positively
      related to film thickness in the 20-40 microm range. Films of 40 microm thickness
      proved to be the most suitable for long-term human UV exposure measurements. The
      temperature independence of the response of 40 microm PPO film was established
      from 1.5 degrees C to 50 degrees C within a dosimeter response uncertainty of
      6.5%. Dose-rate independence was also demonstrated within 8% of the mean
      dosimeter response. The spectral response approximates the CIE erythemal action
      spectrum between 300 and 340 nm, with a peak response at 305 nm. A large
      deviation from this action spectrum was observed at shorter wavelengths.
      Investigation of the angular response in both the azimuth and altitude planes
      showed a cosine error of less than 6.2% between 0 degrees and 40 degrees, and did
      not exceed 13.3% at any angle greater than 40 degrees. These results indicate
      that PPO film satisfies the requirements for use as a UV dosimeter, and may be
      employed in long-term human exposure measurements.

PMID- 14680268
TI  - A three-dimensional breast software phantom for mammography simulation.
AB  - This paper presents a methodology for three-dimensional (3D) computer modelling
      of the breast, using a combination of 3D geometrical primitives and voxel
      matrices that can be further subjected to simulated x-ray imaging, to produce
      synthetic mammograms. The breast phantom is a composite model of the breast and
      includes the breast surface, the duct system and terminal ductal lobular units.
      Cooper's ligaments, the pectoral muscle, the 3D mammographic background and
      breast abnormalities. A second analytical x-ray matter interaction modelling
      module is used to generate synthetic images from monoenergetic fan beams.
      Mammographic images of various synthesized breast models differing in size, shape
      and composition were produced. A preliminary qualitative assessment performed by
      three radiologists and a quantitative evaluation study using fractal and grey
      level histogram analysis were conducted. A comparative study of extracted
      features with published data has also been performed. The evaluation results
      indicated good correlation of characteristics between synthetic and actual
      radiographs. Applications foreseen are not only in the area of breast imaging
      experimentation but also in education and training.

PMID- 14680269
TI  - Effects of magnification and zooming on depth perception in digital
      stereomammography: an observer performance study.
AB  - We are evaluating the application of stereoscopic imaging to digital mammography.
      In the current study, we investigated the effects of magnification and zooming on
      depth perception. A modular phantom was designed which contained six layers of 1
      mm-thick Lexan plates, each spaced 1 mm apart. Eight to nine small, thin nylon
      fibrils were pasted on each plate in horizontal or vertical orientations such
      that they formed 25 crossing fibril pairs in a projected image. The depth
      separation between each fibril pair ranged from 2 to 10 mm. A change in the order
      of the Lexan plates changed the depth separation of the two fibrils in a pair.
      Stereoscopic image pairs of the phantom were acquired with a GE full-field
      digital mammography system. Three different phantom configurations were imaged.
      All images were obtained using a Rh target/Rh filter spectrum at 30 kVp tube
      potential and a +/- 3 stereo shift angle. Images were acquired in both contact
      and 1.8X magnification geometry and an exposure range of 4 to 63 mAs was
      employed. The images were displayed on a Barco monitor driven by a Metheus stereo
      graphics board and viewed with LCD stereo glasses. Five observers participated in
      the study. Each observer visually judged whether the vertical fibril was in front
      of or behind the horizontal fibril in each fibril pair. It was found that the
      accuracy of depth discrimination increased with increasing fibril depth
      separation and x-ray exposure. The accuracy was not improved by electronic
      display zooming of the contact stereo images by 2X. Under conditions of high
      noise (low mAs) and small depth separation between the fibrils, the observers'
      depth discrimination ability was significantly better in stereo images acquired
      with geometric magnification than in images acquired with a contact technique and
      displayed with or without zooming. Under our experimental conditions, a 2 mm
      depth discrimination was achieved with over 60% accuracy on contact images with
      and without zooming, and with over 90% accuracy on magnification images. This
      study indicates that stereoscopic imaging, especially with magnification, may be
      useful for visualizing the spatial distribution of microcalcifications in a
      cluster and for differentiating overlapping tissues from masses on mammograms.

PMID- 14680270
TI  - Wavelet-packet-based texture analysis for differentiation between benign and
      malignant liver tumours in ultrasound images.
AB  - The purpose of this study was to apply a novel method of multiscale echo texture
      analysis for distinguishing benign (hemangiomas) from malignant (hepatocellular
      carcinomas (HCCs) and metastases) focal liver lesions in B-mode ultrasound
      images. In this method, regions of interest (ROIs) extracted from within the
      lesions were decomposed into subimages by wavelet packets. Multiscale texture
      features that quantify homogeneity of the echogenicity were calculated from these
      subimages and were combined by an artificial neural network (ANN). A subset of
      the multiscale features was selected that yielded the highest performance in the
      classification of lesions measured by the area under the receiver operating
      characteristic curve (Az). In an analysis of 193 ROIs consisting of 50
      hemangiomas, 87 hepatocellular carcinomas and 56 metastases, the multiscale
      features yielded a high A: value of 0.92 in distinguishing benign from malignant
      lesions, 0.93 in distinguishing hemangiomas from HCCs and 0.94 in distinguishing
      hemangiomas from metastases. Our new multiscale texture analysis method can
      effectively differentiate malignant from benign lesions, and thus has the
      potential to increase the accuracy of diagnosis of focal liver lesions in
      ultrasound images.

PMID- 14680271
TI  - Rapid calculation of detectability in Bayesian single photon emission computed
      tomography.
AB  - We consider the calculation of lesion detectability using a mathematical model
      observer, the channelized Hotelling observer (CHO), in a signal-known
      exactly/background-known-exactly detection task for single photon emission
      computed tomography (SPECT). We focus on SPECT images reconstructed with Bayesian
      maximum a posteriori methods. While model observers are designed to replace time
      consuming studies using human observers, the calculation of CHO detectability is
      usually accomplished using a large number of sample images, which is still time
      consuming. We develop theoretical expressions for a measure of detectability, the
      signal-to-noise-ratio (SNR) of a CHO observer, that can be very rapidly
      evaluated. Key to our expressions are approximations to the reconstructed image
      covariance. In these approximations, we use methods developed in the PET
      literature, but modify them to reflect the different nature of attenuation and
      distance-dependent blur in SPECT. We validate our expressions with Monte Carlo
      methods. We show that reasonably accurate estimates of the SNR can be obtained at
      a computational expense equivalent to approximately two projection operations,
      and that evaluating SNR for subsequent lesion locations requires negligible
      additional computation.

PMID- 14680272
TI  - Information content and quality of MR thumb images.
AB  - This study investigates the relation between objective and subjective parameters
      which relate to the quality of magnetic-resonance images, with a view to
      developing procedures for minimizing imaging time. The investigation uses high
      resolution images of the thumb as example. Detection thresholds for an artificial
      lesion and ratings of image quality were obtained for a variety of images, with
      several experienced observers. In addition, the information content was
      calculated for each image, using the method developed by Fuderer (1988 IEEE
      Tralns. Med. Imaging 7 368-80). Results suggest that information content can be
      used as a predictor of either detection threshold or quality rating, with a
      critical information content beyond which there is no significant improvement in
      either of these aspects of image quality. Since it is possible to estimate the
      effect of imaging variables on information content, it is possible to predict the
      effect of time-saving imaging strategies on image quality. A procedure is
      suggested for determining the combination of imaging variables which gives the
      shortest possible imaging time whilst retaining image quality.

PMID- 14680274
TI  - Patient-specific planning for prevention of mechanical collisions during
      radiotherapy.
AB  - A common unwanted difficulty in treatment planning, especially in non-coplanar
      radiotherapy set-ups, is the potential collision of the rotating gantry with the
      couch and/or the patient's body. A technique and computer program that detects
      these and signals avoidance of such beam directions is presented. The problem was
      approached using analytical geometry. The separate components within the
      treatment room have either been measured and modelled for an Elekta linear
      accelerator, or read out from a Pinnacle3 treatment planning system and are
      represented as an integer grid of points in three-dimensional (3D) space. The
      module is attached to the treatment planning system and can provide rejection or
      acceptance of unwanted beam directions in a plan. In contrast to previous work
      that has only used patient models, each individual patient's outlines are
      considered here in their actual treatment position inclusive of any
      immobilization device. The extremities of the patient superiorly and inferiorly
      to the scanned region are simulated by an expanded version of the RANDO phantom.
      In this way, 'potential' collisions can be detected in addition to the certain
      ones. Patient position is not a limiting factor for the accuracy of the collision
      detection anymore, as each set-up is always created around the isocentre. Maps of
      allowed and forbidden zones within the treatment suite have been created by
      running the code for all possible gantry and couch angles for three commonly
      arising cases: a head and neck plan utilizing a small stereotactic collimator, a
      prostate plan with multileaf collimators and an abdominal plan with the lead tray
      attached. In the last case, the 3D map permitted significantly fewer set-up
      combinations. Good agreement between prediction and experiment confirmed the
      capability of the program and introduces a promising add-on for treatment
      planning.

PMID- 14680273
TI  - Ridge filter design for proton therapy at Hyogo Ion Beam Medical Center.
AB  - At the Hyogo Ion Beam Medical Center (HIBMC) we have developed a new design
      method for the bar ridge filter used in proton therapy, taking into consideration
      the scattering and nuclear interaction effects within the filter itself, which
      are introduced in the design. In our beam delivery system, the bar ridge filter
      is employed as the range modulator. It is combined with the wobbler system, and
      produces a three-dimensionally uniform spread-out Bragg peak (SOBP). The design
      program predicts the three-dimensional dose distribution. Ridge filters of 3-12
      cm SOBP in 1 cm increments were designed in the maximum radiation field for 150
      MeV and 190 MeV proton beams so that a uniform physical dose area is obtained in
      the SOBP region three-dimensionally. Measurements were performed with the
      constructed ridge filters to verify the uniformity and these were compared with
      the predictions of the design program. The predictions and measurements were
      found to be in agreement except for the 12 cm SOBP. The uniformities were better
      than +/- 3.0% for all SOBPs produced. The ridge filters are now clinically in
      use.

PMID- 14680275
TI  - Scatter-to-primary based scatter fractions for transmission-dependent convolution
      subtraction of SPECT images.
AB  - In single photon emission computed tomography (SPECT), transmission-dependent
      convolution subtraction has been shown to be useful when correcting for scattered
      events. The method is based on convolution subtraction, but includes a matrix of
      scatter fractions instead of a global scatter fraction. The method can be
      extended to iteratively improve the scatter estimate, but in this note we show
      that this requires a modification of the theory to use scatter-to-total scatter
      fractions for the first iteration only and scatter-to-primary fractions
      thereafter. To demonstrate this, scatter correction is performed on a Monte Carlo
      simulated image of a point source of activity in water. The modification of the
      theory is compared to corrections where the scatter fractions are based on the
      scatter-to-total ratio, using one and ten iterations. The resulting ratios of
      subtracted to original counts are compared to the true scatter-to-total ratio of
      the simulation and the most accurate result is found for our modification of the
      theory.

PMID- 14680276
TI  - At the frontiers.

PMID- 14680277
TI  - Recent US and European blood pressure guidelines: implications for developing
      countries.

PMID- 14680278
TI  - A modified technique for the diagnosis of Hirschsprung disease from rectal
      biopsies.
AB  - BACKGROUND: A diagnosis of Hirschsprung disease requires the demonstration of
      acetylcholinesterase fibres on frozen sections obtained from snap frozen biopsies
      of the rectum. This histochemical technique is generally not available in
      laboratories in developing countries. We improvised on the methodology of tissue
      preservation to make the staining technique more user-friendly, economical and
      reliable in demonstrating acetylcholinesterase activity in fresh rectal mucosal
      biopsies for the diagnosis of Hirschsprung disease. METHODS: Between June 1999
      and May 2002 fresh rectal biopsies from 40 suspected cases of Hirschsprung
      disease were processed for routine frozen section (not snap frozen by liquid
      nitrogen) and stained by the Karnovsky and Roots method. These sections were
      assessed for the staining pattern of acetylcholinesterase fibres. The thickness
      of the nerve fibres and muscularis mucosa was assessed morphometrically. These
      were compared with biopsies obtained from 6 age-matched controls undergoing
      surgery for unrelated complaints. RESULTS: The sections stained for
      acetylcholinesterase by this improvised method of tissue fixation were good and
      crisp. A definite diagnosis of Hirschsprung disease was made in 25 cases and
      intestinal neuronal dysplasia in 1. The remaining 14 cases showed an equivocal
      staining pattern with no hypertrophic nerve bundles, thus excluding a diagnosis
      of Hirschsprung disease. The mean thickness of the submucosal nerve trunks
      measured in these enzyme-stained sections was found to be inversely proportional
      to the mean thickness of the muscularis mucosa. CONCLUSION: Our study on cryostat
      cut sections suggests an inverse relationship between the thickness of the
      muscularis mucosa and the calibre of the nerve trunk--thinner the nerve trunk,
      thicker the muscularis mucosa and vice versa. Also, routine frozen sections,
      instead of snap frozen ones taken from a fresh rectal biopsy and stained by the
      Karnovsky and Roots method for acetylcholinesterase activity, are reliable for
      the diagnosis of Hirschsprung disease and are within the capability of a simple
      histopathology laboratory in a developing country.

PMID- 14680279
TI  - Age-related changes in blood lymphocyte subsets of south Indian children.
AB  - BACKGROUND: Enumeration of lymphocyte subsets has been widely used for the
      diagnosis and monitoring of several haematological and immunological disorders.
      Various studies have demonstrated age, sex and racial differences in lymphocyte
      subset expression. Reference values are not available for Indian children and
      there is a need for this information to replace commonly used, but inappropriate,
      adult lymphocyte subset ranges. METHODS: One hundred thirty-eight healthy
      children between 3 and 15 years of age, attending a local government school in
      Chennai, South India were Included in the study. Haemoglobin levels, and total
      and differential cell counts were determined using an automated counter and
      lymphocyte subsets were analysed by flowcytometry. RESULTS: The mean (SD)
      absolute lymphocyte count declined with age from 4338 (1031) at 3 years to reach
      a plateau of 3096 (914) at 11-13 years (p < 0.05). A significant decline was also
      observed in the absolute numbers of CD3+, CD4+, CD8+ and CD19+ cells. However,
      the percentage values of CD3+, CD4+, CD8+, CD16/56+ cells and the CD4/CD8 ratio
      remained fairly stable across the age range. CONCLUSION: Our data would prove
      useful in interpreting disease-related changes in lymphocyte subsets in Indian
      children of different age groups. Age-related decrease in the absolute lymphocyte
      count as well as numbers of CD4 and CD8 cells was found to occur between the ages
      of 3 and 11 years. A normogram relating age to CD4 count has been developed.

PMID- 14680281
TI  - Autologous peripheral blood stem cell transplantation: predictors for
      haematopoietic reconstitution.
AB  - Autologous peripheral blood stem cell transplantation is currently used in the
      treatment of various haematological and non-haematological cancers. Until
      recently, colony forming unit-granulocyte-macrophage (CFU-GM) assay and
      mononuclear cell (MNC) count were the indices commonly used to determine the
      quality of stem cell grafts and the haematopoietic reconstitutive capacity of
      transplanted stem cells. However, the discovery of CD34 as a stem cell marker has
      revolutionized the assessment of progenitor cells present in the peripheral blood
      stem cell graft. Many studies have included enumeration of CD34+ cells, MNCs and
      CFU-GM assay in stem cell grafts, and their correlation with engraftment has also
      been studied. However, there is no consensus regarding the optimum dose of each
      parameter that ensures haematopoietic recovery in all patients. We discuss the
      stem cell biology and review the literature on stem cell characteristics
      influencing successful haemopoietic reconstitution.

PMID- 14680280
TI  - Respiratory paralysis in Sjogren syndrome with normal renal function.
AB  - We report a 28-year-old woman who presented with quadriparesis and respiratory
      failure, and had severe hypokalaemia and distal renal tubular acidosis. She
      recovered completely on potassium and alkali supplementation. Biopsy and
      scintigraphy of the minor salivary glands confirmed the presence of Sjogren
      syndrome. A 6-month course of prednisolone did not correct the distal renal
      tubular acidosis.

PMID- 14680282
TI  - Nucleic acid amplification tests for tuberculous meningitis: a systematic review
      of diagnostic accuracy.

PMID- 14680283
TI  - The Ugandan response to HIV/AIDS: some lessons for India.
AB  - During the 1980s and 1990s, Uganda faced a severe crisis, with almost 30% of the
      adult population infected with HIV/AIDS. Uganda responded through a mix of
      rationalist and creative policy approaches which, after a decade of intervention,
      made Uganda the first African nation to report a decline in HIV prevalence--a
      trend that continues till today. Uganda thus demonstrated to the world that
      success is possible in the war against HIV/AIDS. I analyse here the Ugandan
      response to the HIV/AIDS epidemic and highlight some lessons to be learnt for
      countries such as India, which face a rising HIV/AIDS epidemic. It is in the
      creative policy initiatives, often called the unwritten policy response, that
      major lessons are to be learnt from Uganda. Lessons may also be learnt by other
      nations from certain weaknesses in the Ugandan approach.

PMID- 14680284
TI  - Misunderstanding depression.

PMID- 14680285
TI  - Books a doctor must read.

PMID- 14680286
TI  - Health technology assessment in Scotland.

PMID- 14680287
TI  - Steadfast to the summit: living and climbing at altitude.

PMID- 14680288
TI  - Controversies of cola beverages.

PMID- 14680289
TI  - 'Bugged' phones.

PMID- 14680291
TI  - Avian endogenous retroviruses.
AB  - Recent data about the diversity of AER, their structure, expression and possible
      ways of evolution are summarized and analysed in the present review.
      Additionally, the role of endogenous retroviruses in ontogenesis and pathology is
      discussed.

PMID- 14680290
TI  - Imatinib mesylate-induced maculopapular drug rash.

PMID- 14680292
TI  - Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell
      cancer patients compared with systemic interleukin-2: an outcome study.
AB  - Systemic IL-2 is an effective treatment for low to intermediate risk mRCC
      patients, its efficacy is marginal in high-risk cases. Therefore, other treatment
      approaches are required for this population. Ninety-four high-risk patients with
      RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose
      subcutaneous rhIL-2. Clinical response, survival and safety were compared with
      those from IL-2 given systemically at the registered dose and schedule in 103
      comparable historical controls. In the rhIL-2 INH group, treatment consisted of
      6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS
      group received treatment which consisted of intravenous infusion of 18.0
      MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both
      groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH
      and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression
      free survival durations were observed in the rhIL-2 INH group. The probability of
      survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5
      years in the rhIL-2 SYS group. A multivariate analysis of overall survival
      adjusting for differences in baseline characteristics between the two treatment
      groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data
      suggested an association between the response (SD or better) and survival,
      especially in the rhIL-2 INH group. The inhalation regimen was well tolerated.
      This outcome study suggests that administration of rhIL-2 by inhalation is
      efficacious and safe in high-risk mRCC patients with pulmonary metastases, who
      have no other treatment option available.

PMID- 14680293
TI  - Gamma irradiation results in phosphorylation of p53 at serine-392 in human T
      lymphocyte leukaemia cell line MOLT-4.
AB  - Exposure of human leukaemia MOLT-4 cells to ionizing irradiation led to
      apoptosis, which was detected by flow cytometric analysis and degradation of the
      nuclear lamina. The multiple signalling pathways triggered by either membrane or
      DNA damage play a critical role in radiation-induced apoptosis. The response to
      DNA damage is typically associated with the p53 protein accumulation. In this
      study, we proved that the transcriptionally active p53 variant occurs in the MOLT
      4 cells and its abundance alteration is triggered in the gamma-irradiated cell
      population concomitantly with phosphorylation at both the serine-392 and serine
      15 residues. The p21 upregulation followed the p53 phosphorylation process in
      irradiated MOLT-4 cells.

PMID- 14680294
TI  - UVC-protective effect of caffeic acid on normal and transformed human skin cells
      in vitro.
AB  - Possible UVC-protective properties of CA, a plant phenolic compound with
      antioxidant activity, were investigated on human KF1 diploid fibroblast and A431
      epidermoid carcinoma cell lines. Cell populations, untreated and treated by
      antioxidants (CA and alpha-tocopherol), were irradiated by UVC at the wavelength
      of 254 nm and their proliferation activity was determined by the MTT assay. The
      results show a strong protective effect of CA at both concentrations used (55.5
      and 166.5 microM): a significant increase of proliferation activity after UVC
      irradiation was detected in both cell populations growing in the presence of CA
      in comparison with cells in DMEM only. The described protective effect of CA was
      more obvious in transformed cells than in normal diploid cells. This protective
      ability is probably based on the antioxidant and scavenging activities of CA,
      which seems to be more efficient than alpha-tocopherol in protection against the
      cytotoxic effect caused by UVC irradiation.

PMID- 14680295
TI  - Immunotherapy of HPV 16-associated tumours with tumour cell line/dendritic cell
      line (TC-1/DC2.4) hybrid vaccines.
AB  - Hybridization of established dendritic cell lines with tumour cells represents a
      prospective technology for the construction of antitumour vaccines. Experiments
      were designed to examine whether administration of cell populations prepared by
      fusion of HPV 16-associated tumour TC-1 cells with dendritic cell line DC2.4
      could be used for treatment of TC-1 tumours growing in syngeneic mice. The
      therapeutic potency of TC-1/DC2.4 fusion vaccine administered 24 h after fusion
      and that of TC-1/DC2.4 hybrid cells selected for 3 weeks in HAT-containing medium
      was tested. It has been found that administration of both types of fusion
      vaccines at the site of growing TC-1 tumour transplants significantly inhibited
      tumour growth with regard to the percentage of tumour-bearing mice and to the
      size of the transplanted tumours. Peritumoral administration of the DC2.4 cells
      alone also reduced the size of growing TC-1 tumours, but not the percentage of
      the tumour-bearing mice. Although in the groups of mice treated with fusion
      vaccines the size of the tumours was reproducibly smaller than that in the mice
      treated with parental DC2.4 cells, the difference was not statistically
      significant.

PMID- 14680296
TI  - Effects of adenosine on the growth of murine G:5:113 fibrosarcoma cells in vitro.
AB  - It has been observed that adenosine suppresses the growth of G:5:113 murine
      fibrosarcoma cells in vitro with EC50 of 178 mM. Changes in the cell cycle
      including decreased percentage of cells in S-phase, increased portion of cells in
      G0/G1-phase, as well as prolonged generation time were found to be responsible
      for the growth suppression. Dipyridamole, a drug inhibiting the cellular uptake
      of adenosine, enhanced the growth suppression induced with adenosine in
      concentrations of 100 and 200 microM. It follows from these results that the
      action of adenosine on the G:5:113 cells is extracellular, mediated by adenosine
      receptors. Elevation of extracellular adenosine might serve potentially as an
      anticancer therapeutic agent.

PMID- 14680297
TI  - Calf deep venous thrombosis should be treated with anticoagulation.
AB  - A 50-year-old man with hypertension presents with a 2-day history of right calf
      swelling and pain. Venous duplex ultrasound reveals a right soleal vein
      thrombosis. He denies history of bleeding, renal disease, and symptoms suggestive
      of pulmonary embolism (PE). Physical examination is unrevealing except for calf
      tenderness, redness, warmth, and swelling. He is ambulatory. A decision is made
      to treat the calf deep venous thrombosis (DVT) with anticoagulation.

PMID- 14680298
TI  - Young patients with iliofemoral deep venous thrombosis should receive
      thrombolytic therapy.
AB  - A 20-year-old otherwise healthy woman on oral contraceptive pills presents with
      sudden-onset left leg swelling and pain extending from her calf to her groin.
      Pulmonary embolism symptoms are lacking. Venous duplex ultrasound reveals acute
      deep venous thrombosis (DVT) involving the distal external iliac, common femoral,
      superficial femoral, and popliteal veins. Her leg is markedly swollen, slightly
      cool to the touch, but has preserved pedal pulses. She is unable to ambulate
      secondary to pain. Thrombolytic therapy to eliminate the DVT is recommended.

PMID- 14680299
TI  - Patients undergoing surgical resection of primary brain tumors should receive
      pharmacologic venous thromboprophylaxis.
AB  - A 58-year-old woman presents with headache, mental status changes, and new-onset
      generalized seizures. MRI of the brain reveals a frontoparietal enhancing mass
      lesion suggestive of glioblastoma multiforme. Craniotomy for diagnosis,
      debulking, and likely placement of chemotherapy-impregnated wafers is planned.
      Venous thromboprophylaxis is prescribed.

PMID- 14680300
TI  - Patients with inferior vena caval filters should receive chronic
      thromboprophylaxis.
AB  - A 32-year-old man with testicular carcinoma is diagnosed with an acute left leg
      deep venous thrombosis (DVT) during his fourth cycle of combination chemotherapy.
      Because of anticipated moderate to severe thrombocytopenia, anticoagulation is
      initially avoided and an inferior vena cava (IVC) filter is placed to prevent
      pulmonary embolism (PE). After completion of all chemotherapy he is deemed to be
      in remission and anticoagulation is begun. The optimal duration of
      anticoagulation in this patient is pondered.

PMID- 14680301
TI  - Should patients on warfarin for 3 months for idiopathic proximal deep venous
      thrombosis receive bridging therapy precolonoscopy (with expected biopsy)?
AB  - A 63-year-old woman presents to discuss periprocedure anticoagulation management.
      She has been on oral warfarin with an international normalized ratio between 2
      and 3 for the past 3 months because of an idiopathic left popliteal vein
      thrombosis. A colonic polyp was identified during her purely diagnostic
      colonoscopy performed as part of her age- and gender-appropriate cancer
      screening. Immediate repeat colonoscopy with polypectomy is recommended. The
      clinician is asked to provide periprocedural anticoagulation recommendations.

PMID- 14680302
TI  - A positive in vitro assay is required to diagnose heparin-induced
      thrombocytopenia.
AB  - A 57-year-old woman is admitted for coronary artery bypass graft. She has had a
      recent coronary angiogram (with heparin exposure), which revealed high-grade
      stenoses of the left anterior descending coronary artery, right coronary artery,
      and left circumflex artery. The preoperative platelet count is 300,000/microL.
      Heparin is administered during cardiopulmonary bypass. The platelet count on
      postoperative day 1 is 160,000/microL and on postoperative day 6 is
      60,000/microL. Heparin-induced thrombocytopenia (HIT) is suspected and HIT assays
      are ordered.

PMID- 14680304
TI  - Comprehensive hypercoagulable state testing is indicated in patients with a first
      idiopathic deep venous thrombosis.
AB  - A 45-year-old man presents with a 3-day history of right leg swelling and pain.
      He is diagnosed with an acute right common femoral vein thrombosis. He takes no
      medications, has an unremarkable medical history, no recent trauma or surgery, no
      recent travel, and no known cancer. Performance of a comprehensive
      hypercoagulable state panel is contemplated.

PMID- 14680303
TI  - Estrogen-containing oral contraceptives are allowable in young women with factor
      V Leiden heterozygosity without a history of thrombosis.
AB  - An 18-year-old woman without significant past medical and surgical history
      presents to discuss the safety and efficacy of oral contraceptives. She is
      sexually active and currently relying on condoms alone for birth control. Her
      cousin had a deep venous thrombosis (DVT) following a pregnancy. As part of the
      family screening, this patient was identified as a factor V Leiden heterozygote.
      The risks and benefits of initiating oral contraceptives are discussed.

PMID- 14680305
TI  - Patients with acute pulmonary embolism should have an echocardiogram to guide
      treatment decisions.
AB  - A 62-year-old man with a past medical history notable for hypertension,
      osteoarthritis, and calf deep vein thrombosis at age 55 following a total hip
      arthroplasty presents to the emergency department with acute-onset dyspnea and
      right-sided pleuritic chest pains. His medications consist of a calcium channel
      blocker and a COX-2 inhibitor. Pretest clinical suspicion for pulmonary embolism
      (PE) is high. Ventilation and perfusion lung scintigraphy are interpreted as
      being high-probability for PE. The nurse asks if a stat transthoracic
      echocardiogram should be ordered.

PMID- 14680306
TI  - Populations at high risk for prostate cancer.
AB  - Although prostate cancer tends to be a slow-growing neoplasm affecting older men,
      there is clearly a subset of patients at high risk for developing early and
      possibly more aggressive disease. This group of high-risk patients includes men
      with a family history of prostate cancer and various histologic features such as
      PIN and ASAP identified on an initial biopsy. Black American men have a much
      higher risk of developing prostate cancer when compared with white men and
      especially Asian men. This finding may reflect both genetic and environmental
      factors. Screening men at increased risk of developing prostate cancer appears to
      be a logical strategy, especially in light of recent reports that suggest a
      benefit to aggressive treatment.

PMID- 14680307
TI  - PSA markers in prostate cancer detection.
AB  - The PSA revolution that has occurred over the previous 2 decades has positively
      impacted the detection and treatment of men with prostate cancer. Although
      methods to improve specificity have shown promise (eg, PSAD, age-specific PSA,
      and PSA velocity), meaningful interpretation has yet to be uniformly accepted
      within clinical practice. The identification of other molecular forms of PSA
      within serum has led to a new era in PSA markers. Initial application employing
      %fPSA has provided improved discrimination between benign and malignant prostatic
      disease; however, questions remain regarding the ultimate threshold value. The
      discovery of various free forms of PSA--such as proPSA, BPSA, and iPSA--also have
      introduced the potential for improved specificity in detection. Although early
      results are encouraging, further evaluation is anticipated. The development of
      improved methods to detect and measure cPSA has demonstrated provocative results,
      and exhibits the potential to replace PSA as a standard diagnostic test in cancer
      screening.

PMID- 14680308
TI  - Follow-up of conservatively managed prostate cancer: watchful waiting and primary
      hormonal therapy.
AB  - Many men with newly diagnosed prostate cancer choose not to undergo curative
      treatment, including patients who cannot be helped by local curative therapies
      (especially those with metastatic disease) and patients with clinically localized
      disease who opt for expectant management or noncurative treatments such as
      androgen ablation. This article reviews the selection of patients for these
      noncurative approaches, strategies for clinical monitoring, the choices of
      intervention therapies upon progression, and when to start these therapies.

PMID- 14680309
TI  - Prostate cancer: radical prostatectomy.
AB  - Today, more men than ever before are being followed after radical prostatectomy.
      Prognosis and follow-up should be based on the pathologic specimen. Measurable
      prostate-specific antigen (PSA) after surgery defines failure, with time to
      detectable PSA and rate of PSA rise being useful prognostic factors. The natural
      history of untreated biochemical failure is protracted, a fact to be considered
      in discussions of adjuvant treatment. Early in disease recurrence, imaging
      studies to locate residual disease rarely are useful clinically. Both adjuvant
      and salvage radiation to the prostate bed have benefits and risks, but neither is
      superior in overall prostate cancer survival. The timing of hormone therapy
      remains largely empiric. The promise of effective cytotoxic chemotherapy still is
      greater than its actual benefits, although novel cytostatic agents are being
      developed. The future management of this disease will improve with better
      molecular definition of risk and therapeutic response.

PMID- 14680310
TI  - Prostate cancer: cryotherapy.
AB  - The incidence of prostate cancer has more than doubled in the last 10 years, and
      220,900 new cases will be detected in 2003. This increase is due in large part to
      increased use of prostate-specific antigen (PSA)-based screening, transrectal
      ultrasonography, and random biopsy of the prostate. The treatment of prostate
      cancer, however, remains controversial, and no consensus has been established as
      to what constitutes appropriate treatment for any stage of disease, especially
      for localized cancers. Radical prostatectomy, radiation therapy, or watchful
      waiting all have their advocates, and the risks and benefits of these approaches
      are discussed frequently. Skepticism about conventional treatments has stimulated
      patients and physicians to search for alternatives that are effective and
      associated with limited morbidity. Technologic developments have rekindled
      interest in cryotherapy as a viable alternative to other, more conventional
      localized therapies. Given the relative paucity of alternatives for patients who
      experience biochemical progression after radiotherapy, cryosurgery also may prove
      to be a good alternative for those patients whose tumors appear to remain
      localized despite progression. In addition, it appears that cryosurgery will play
      an increased role in the future management of prostate cancer.

PMID- 14680311
TI  - Brachytherapy for prostate cancer: follow-up and management of treatment
      failures.
AB  - The use of prostate brachytherapy for the treatment of early-stage, low-grade,
      low-volume carcinoma of the prostate continues to rise. Given the prolonged
      natural history of these early lesions, treatment failures may take many years or
      even a decade or more before becoming clinically evident. It is therefore likely
      that as the brachytherapy data mature, clinicians will be asked to help manage a
      potentially large cohort of men who have failed this local therapy--a scenario
      that will provide a number of unique challenges for the treatment of the disease
      and the management of the lower urinary tract. This article offers a contemporary
      review and suggestions with regard to the follow-up of patients who have
      undergone prostate brachytherapy, including low-dose rate permanent implants and
      high-dose rate temporary implants for the management of localized prostate
      cancer. In addition, current controversies in defining biochemical failure
      following radioactive implantation--including important data regarding the
      "prostate-specific antigen bounce" phenomenon--are discussed. Finally, a
      comprehensive review of the management of local recurrence following
      brachytherapy is offered.

PMID- 14680312
TI  - Recurrent prostate cancer following external beam radiotherapy: follow-up
      strategies and management.
AB  - All patients who undergo curative therapy for prostate cancer should be followed
      for a prolonged period of time to determine tumor control and treatment toxicity
      for quality assurance purposes. Follow-up duties may be reasonably shared between
      the oncologist and the family doctor or urologist: however, it is probable that
      some follow-up information specific to the irradiated patient will be lost unless
      the oncologist maintains regular contact with the patient, especially in the
      first 5 years of follow-up when late radiation effects are most likely to appear.
      There is no strong evidence that patients stop being at risk for recurrence at
      any time after treatment, and because PSA testing is an accurate, simple, and
      inexpensive method of determining post-RT tumor status, it is recommended that
      periodic PSA measurements be continued for life. In the absence of a rising PSA,
      all other tests and visits are unnecessary to determine post-RT tumor control.
      Because DRE has been shown to be of limited utility in follow-up of irradiated
      patients, it should be possible to effectively follow patients remotely. This
      could be done by asking patients to have PSA tests done, forward the results to
      their physicians, and report treatment toxicity when it occurs. Only abnormal
      results would trigger an office visit. This strategy is being evaluated in
      clinical trials. The alternative is to delegate the follow-up to the primary-care
      physician with guidelines as to when referral back is required. Follow-up
      frequency, and the most beneficial follow-up investigations vary from scenario to
      scenario, and are influenced by the likelihood of relapse, time to relapse, and
      planned intervention. These decisions are influenced in turn by the initial
      presentation--either with high or low risk factors--and by the patient's general
      state of health at completion of EBRT. Effective follow-up also requires active
      patient cooperation that only can be achieved after discussion of the goals of
      follow-up with the patient and with the patient's full understanding of the
      process. The follow-up strategy proposed in Fig. 1 is most suitable for a fit
      patient with low or intermediate risk factors who wishes to consider all salvage
      options should he relapse, or for the high-risk individual in situations in which
      the probability of systemic relapse is of major concern. Young patients with very
      adverse risk factors may benefit from even closer follow-up in the early years
      after EBRT and the elderly or frail may require only occasional visits to record
      or treat treatment toxicity and to ensure clinical non-progression.

PMID- 14680313
TI  - Evaluation and follow-up strategies for superficial bladder cancer.
AB  - Superficial bladder cancer comprises the majority of bladder tumors presenting
      today. Although the word "superficial" connotes a benign behaving curable
      disease, it is clear from long-term observations of the natural history of the
      disease that there are two discrete entities of superficial bladder cancer, one a
      low-grade innocuous tumor and the other a high-grade potentially lethal tumor.
      These two entities vary in their histologic appearance, risk of tumor recurrence,
      pattern of recurrence, and risk of tumor progression. Although work on prognostic
      markers is promising, currently none are sufficiently reliable; therefore,
      clinical factors are used to identify patients with a higher risk of tumor
      recurrence or progression. These include the tumor stage, tumor grade, number of
      tumors (multifocality), presence of associated carcinoma in situ, and initial
      response to therapy. Surveillance schedules are individualized based on the risks
      for recurrence and progression. High-risk patients who undergo successful
      treatment of their bladder tumor initially recur more commonly in the bladder,
      but have a progressive risk over time of extravesical recurrences necessitating
      lifelong surveillance of the bladder, urethra, prostate, and upper tracts.
      Patients who are refractory to conservative management with intravesical therapy
      and TUR should be apprised of the risks for further conservative treatment and
      consider early radical cystectomy in an attempt to improve long-term survival.
      The advent and long-term success of orthotopic continent diversions has made the
      decision for early radical cystectomy more palatable to both the patient and
      physician.

PMID- 14680314
TI  - Follow-up strategies and management of recurrence in urologic oncology bladder
      cancer: invasive bladder cancer.
AB  - A surveillance program following cystectomy should consider a patient's
      individual risk for the development of local and distant recurrences and any
      specific needs related to the urinary tract reconstruction performed (Table 1).
      Well-documented recurrence patterns following cystectomy are available from many
      large surgical series and provide the background information needed for tailoring
      follow-up based on pathologic criteria. Economic issues also must be considered,
      given that the health care-related expenses of treating and following patients
      with bladder cancer is twice as much as that expended for the treatment of
      prostate cancer. Because of the ever-increasing fiscal constraints placed on
      clinicians, risk-adjusted follow-up strategies are reasonable, but will require
      prospective evaluation to validate their appropriateness.

PMID- 14680315
TI  - Surveillance and management of recurrence for upper tract transitional cell
      carcinoma.
AB  - Surveillance of treated upper tract TCC must be tailored to each patient based on
      individual tumor characteristics. Important risk factors include tumor stage,
      grade, and multifocality. Molecular markers for TCC may assist in future
      surveillance strategies, but for now remain experimental. Improvements in imaging
      eventually may provide the sensitivity needed to determine tumor stage, which
      would make both initial and recurrence management decisions much more accurate.
      Initial surgical treatment will influence surveillance when it pertains to
      superficial disease treated conservatively with either open segmental resection
      or, now more commonly, with endoscopic resection. Patients treated in this manner
      require vigilant surveillance of the ipsilateral ureter. Direct visualization in
      combination with cytology currently appears to be the most effective method,
      using the same timelines as those used for bladder TCC. Prospective studies
      concerning surveillance protocols for upper tract TCC would certainly provide
      more evidence for the current recommendations. However, the evidence does show
      that upper tract TCC behaves biologically much in the same fashion as does
      bladder TCC. In light of this fact, the current recommendations are meant to
      suggest following a patient after treatment for upper tract TCC in a manner
      similar to that used to follow a patient after treatment of bladder TCC, with
      individual strategies based on tumor characteristics. For superficial disease,
      the technology now exists to moniter a patient after endoscopic resection of an
      upper tract tumor in exactly the same manner used to follow a patient after
      endoscopic resection of a bladder tumor.

PMID- 14680316
TI  - Management of recurrence and follow-up strategies for patients with seminoma and
      selected high-risk groups.
AB  - Seminoma is characterized by high sensitivity to both radiation and chemotherapy.
      Localized recurrences in the retroperitoneum after surveillance for stage I can
      be treated with radiotherapy; however, multiple or large bulky retroperitoneal
      recurrences or systemic metastasis requires cisplatin-based chemotherapy. Salvage
      chemotherapy for those who recur after initial CR to induction chemotherapy is
      based on ifosfamide- and cisplatin-containing regimens. Incomplete response or
      failure after induction chemotherapy requires high-dose chemotherapy and stem
      cell rescue. Patients with seminoma need long-term follow-up because of the
      possibility of late recurrence and the risk of a second primary tumor.

PMID- 14680317
TI  - Management of recurrence and follow-up strategies for patients with nonseminoma
      testis cancer.
AB  - This review serves as an outline of the clinical features and management options
      for the majority of recurrence situations in NSGCTs. The combination of reliable
      serum tumor markers, improved imaging techniques, effective cisplatin
      chemotherapy regimens, and application of meticulous surgical techniques has
      resulted in dramatic improvements in cure rates in NSGCT. These factors have
      caused the incidence of recurrent NSGCT to decline substantially in the past 20
      years. This rarity of recurrence in combination with the low incidence of NSGCT
      prevents the practicing clinician from accumulating experience in this
      challenging patient population. Therefore, to ensure improvement in salvage
      rates, patients are best managed in centers with extensive experience in NSGCT.

PMID- 14680318
TI  - Hereditary kidney cancer.
AB  - Significant advances have been made in the understanding of the genetic basis of
      familial renal neoplasia. Identification of key genes in the pathogenesis of
      various hereditary renal cancer syndromes has provided opportunities to screen
      family members at risk and to explore the significance of these genetic
      abnormalities in the development and genesis of much more common sporadic
      counterparts. As researchers continue to delineate critical carcinogenic pathways
      and accumulate expansive knowledge on oncogenic mechanisms driving cancer
      initiation and progression at the cellular and molecular levels, this information
      will be integrated and translated into effective diagnostic and therapeutic
      strategies that will dictate clinical management of all renal cancers.

PMID- 14680319
TI  - Surveillance after radical or partial nephrectomy for localized renal cell
      carcinoma and management of recurrent disease.
AB  - Surveillance after surgery for RCC is important because approximately 50% of
      these patients will develop a disease recurrence, two thirds of who will recur
      within the first year. Although the prognosis is generally poor in these
      patients, some may respond favorably to immunotherapy. The small subset of
      patients who develop solitary metastases has the greatest chance to achieve long
      term survival. Aggressive surgical resection is an integral part of this success.
      Proposed surveillance protocols using a stage-based approach or an integrated
      approach combining stage with other important prognostic factors attempt to
      provide a rational approach to identifying treatable recurrences while minimizing
      unnecessary examinations and patient anxiety. However, strict adherence to follow
      up guidelines may not be appropriate for all patients. Factors including patient
      comorbidities and patient willingness to pursue aggressive management in the
      event of recurrence may alter the follow-up for each individual.

PMID- 14680320
TI  - Natural history, management, and surveillance of recurrent squamous cell penile
      carcinoma: a risk-based approach.
AB  - For men with penile carcinoma, surveillance strategies may be tailored to the
      risks of local and regional recurrence, which vary according to the pathologic
      characteristics of the primary tumor and the modalities employed for local
      therapy (phallus sparing or extirpative) and regional therapy (surveillance or
      lymphadenectomy). Men at a higher risk for local or regional recurrence who
      should have more rigorous follow-up include those (1) treated with phallus
      sparing strategies such as laser ablation, topical therapies, or radiotherapy;
      (2) patients with clinically negative inguinal lymph nodes who are managed
      without lymphadenectomy despite high-risk primary tumors (pT2-3, grade 3,
      vascular invasion); and (3) those with lymph node metastases after
      lymphadenectomy. Good candidates for less-stringent surveillance include patients
      with low-risk primary tumors (pTis, pTa, pT1, grades 1-2) and those with negative
      inguinal nodes after lymphadenectomy whose primary tumors were managed with
      partial or total penectomy.

PMID- 14680321
TI  - Follow-up and management of recurrent Wilms' tumor.
AB  - Over the past 3 decades, enormous advances have been made in the creation of a
      standardized treatment protocol for Wilms' tumor. Less morbid regimens for low
      risk patients and more efficacious aggressive treatment protocols for high-risk
      patients have been developed, and continue to be improved with newer studies,
      such as the NWTS-V. An area that has posed a more challenging aspect of the
      disease is its relapse. Although a standard follow-up protocol has been produced
      by in-depth evaluation of previous works, there has been a great deal of
      difficulty demonstrating improved relapse-free and overall survival rates in re
      treatment of children suffering from recurrent Wilms' tumor. Several factors are
      involved in the success of treatment of relapse, some of which include prerelapse
      treatment of initial disease and stage, site, and timing of recurrence. New
      agents and their combination with chemotherapeutics that already have established
      efficacy are being used for treatment of Wilms' tumor relapse, with varying
      success. These studies should lead the way for newer investigations in the
      future. Patients with anaplastic disease, rhabdoid tumors, and clear cell sarcoma
      are especially in need of these future investigations. Perhaps the true final
      frontier is establishing the likelihood of patients suffering a relapse. This
      topic currently is being studied in the fields of biologic markers and gene
      expression. This knowledge will hopefully, in turn, tailor initial treatment in a
      more specific manner.

PMID- 14680322
TI  - Neuroblastoma: management, recurrence, and follow-up.
AB  - The clinical use of N-myc amplification in neuroblastoma management has served as
      a paradigm for "bench to bedside" medicine. It is hoped that the quest for
      molecular markers such as neurotrophin, TrkA, and TrkB will continue to advance
      the understanding of neuroblastoma. In addition, animal models of neuroblastoma
      (N-myc transgenic mice, and neuroblastoma xenografts) have been established to
      assess the efficacy of novel treatments. These advances are likely to improve
      clinical practice in the future.

PMID- 14680323
TI  - Playing in the mud-using gene expression to assess contaminant effects on
      sediment dwelling invertebrates.
AB  - Bioaccumulation and toxicity tests using benthic invertebrates such as the
      estuarine amphipod Leptocheirus plumulosus are typically used to assess the
      ecological risk associated with contaminated sediments. Despite their ecological
      and regulatory importance, little is known about such species at the genetic
      level. To begin understanding cellular and genetic responses of L. plumulosus to
      contaminants, we isolated several of their genes and developed quantitative
      assays to measure the effects of water exposures to 2, 4, 6-trinitrotoluene and
      phenanthrene on gene expression. Real-time polymerase chain reaction (PCR) assays
      demonstrated that the expression of the genes for actin and a retrotransposon,
      hopper, was dependent on the exposure and tissue concentrations of those
      chemicals. Our data suggests that exposure to the explosive 2, 4, 6
      trinitrotoluene and phenanthrene may induce movement of hopper resulting in
      unexpected genotoxic results.

PMID- 14680324
TI  - The path from molecular indicators of exposure to describing dynamic biological
      systems in an aquatic organism: microarrays and the fathead minnow.
AB  - The extent to which humans and wildlife are exposed to toxicants is an important
      focus of environmental research. This work has been directed toward the
      development of molecular indicators diagnostic for exposure to various stressors
      in freshwater fish. Research includes the discovery of genes, indicative of
      environmental exposure, in the Agency's long-established aquatic toxicological
      organism, the fathead minnow (Pimephales promelas). Novel cDNAs and coding
      sequences will be used in DNA microarray analyses for pattern identification of
      stressor-specific, differentially up- and down-regulated genes. The methods
      currently used to discover genes in this organism, for which few annotated
      nucleic acid sequences exist, are cDNA subtraction libraries, differential
      display, exploiting PCR primers for known genes of other members of the family
      Cyprinidae and use of degenerate PCR primers designed from regions of moderate
      protein homology. Single or multiple genes noted as being differentially
      expressed in microarray analyses will then be used in separate studies to measure
      bioavailable stressors in the laboratory and field. These analyses will be
      accomplished by quantitative RT-PCR. Moving from analysis of single gene
      exposures to the global state of the transcriptome offers possibilities that
      those genes identified by DNA microarray analyses might be critical components of
      dynamic biological systems and networks, wherein chemical stressors exert toxic
      effects through various modes of action. Additionally, the ability to
      discriminate bioavailability of stressors in complex environmental mixtures, and
      correlation with adverse effects downstream from these early molecular events,
      presents challenging new ground to be broken in the area of risk assessment.

PMID- 14680325
TI  - Analysis of gene expression profiles in largemouth bass exposed to 17-beta
      estradiol and to anthropogenic contaminants that behave as estrogens.
AB  - Novel molecular based methods are being developed to study changes in gene
      expression in wildlife exposed to anthropogenic chemicals. Gene arrays, in
      particular, are useful tools that can be used to simultaneously monitor hundreds
      to thousands of genes within a single experiment, giving an investigator the
      ability to determine how exposure affects multiple metabolic pathways. These
      methods are thought to be both sensitive and able to reveal biochemical
      mechanisms of action. A largemouth bass (LMB) array containing 132 genes has been
      designed to study the impact of gene expression in male fish exposed to 17-beta
      estradiol or to the compounds 4-nonylphenol (4-NP) or 1,1-dichloro-2, 2-bis (p
      chlorophenyl) ethylene (p,p'-DDE). The results of these experiments demonstrate
      distinct gene expression patterns in LMB exposed to these compounds.

PMID- 14680326
TI  - DNA microarrays detect 4-nonylphenol-induced alterations in gene expression
      during zebrafish early development.
AB  - Technological advances in the biological sciences have led to a growing
      realization of the inherent complexity of the toxic actions of man-made chemicals
      and industrial compounds. An organism's response to toxic exposure is often a
      complex summation of the individual responses of various different cell types,
      tissues, and organs within an individual. Furthermore, within a population,
      various factors including gender, age, fitness, exposure history, genetic
      variation, and developmental stage significantly affect how each individual will
      react following exposure. Because of this complexity, characterizing the
      responses of organisms to environmental toxin exposure is an area of research
      well suited to the utilization of the gene-expression profiling capability of DNA
      microarrays. Microarrays are capable of screening large numbers of genes for
      response to environmental exposure, with the resulting genesets comprising de
      facto biomarkers for such exposures. In many cases, the genesets described
      contain response transcripts anticipated from known mechanistic pathways, but in
      other cases, equally indicative biomarkers may be found that are unexpected. We
      investigated the response of zebrafish embryos exposed in vitro to the
      environmental contaminant 4-nonylphenol (4NP). Nonylphenol is one of several
      alkylphenol ethoxylate compounds widely used in agricultural and industrial
      processes that have become ubiquitous environmental contaminants. By combining
      data from differing levels of exposure, we have identified a group of genes that
      appear indicative of embryo exposure to 4NP at concentrations ranging from high
      near-lethal levels to lower, more environmentally relevant levels. These
      biomarker sets can be further expanded and adapted for use in environmental
      monitoring as well as in mechanistic studies of complex toxicological mechanisms
      during both early and adult developmental stages.

PMID- 14680327
TI  - Gene expression profiling in ecotoxicology.
AB  - Gene expression profiling is a powerful new end point for ecotoxicology and a
      means for bringing the genomics revolution to this field. We review the
      usefulness of gene expression profiling as an end point in ecotoxicology and
      describe methods for applying this approach to non-model organisms. Since genomes
      contain thousands of genes representing hundreds of pathways, it is possible to
      identify toxicant-specific responses from this wide array of possibilities.
      Stressor-specific signatures in gene expression profiles can be used to diagnose
      which stressors are impacting populations in the field. Screening for stress
      induced genes requires special techniques in organisms without sequenced genomes.
      These techniques include differential display polymerase chain reaction (DD PCR),
      suppressive subtractive hybridization PCR (SSH PCR), and representational
      difference analysis. Gene expression profiling in model organisms like yeast has
      identified hundreds of genes that are up-regulated in response to various
      stressors, including several that are well characterized (e.g., hsp78,
      metallothionein, superoxide dismutase). Using consensus PCR primers from several
      animal sequences, it is possible to amplify some of these well characterized
      stress-induced genes from organisms of interest in ecotoxicology. We describe how
      several stress-induced genes can be grouped into cDNA arrays for rapidly
      screening samples.

PMID- 14680328
TI  - Proteomics in zebrafish exposed to endocrine disrupting chemicals.
AB  - Embryonic zebrafish were examined for changes in protein expression following
      exposure to sublethal concentrations of 17beta-estradiol (E2) and the estrogen
      mimic 4-nonylphenol (4-NP). Protein Expression Signatures were derived from
      embryo homogenates by two-dimensional electrophoresis and digital imaging. In
      both experiments approximately 30% of the proteins sampled were specific to
      either E2 or 4-NP and about 33% were common to the control, 4-NP and E2. However,
      of the proteins induced by either E2 or 4-NP, 28% were common to both chemicals
      at 1 ppm but only 7% were common to both at 0.1 ppm. While there are many
      proteins that respond specifically to each chemical, relatively few are common to
      the two chemicals suggesting that the response pathways of the two chemicals are
      distinct.

PMID- 14680329
TI  - The genomic revolution: what does it mean for human and ecological risk
      assessment?
AB  - The first sequencing of a complete organism genome occurred in 1995. Since then
      there has been an explosion of information, with a new organism being sequenced
      nearly every week. This rapid development of genomics is providing unparalleled
      opportunities in toxicology, ecology, and risk assessment. This paper provides an
      overview of some possible applications of this new information in ecological and
      human risk assessment.

PMID- 14680330
TI  - Biotransfer of selenium: effects on an insect predator, Podisus maculiventris.
AB  - The effects of selenium (Se) accumulation in phytophagous insects on predators in
      the next trophic level were investigated. The generalist predator Podisus
      maculiventris Say (Hemiptera: Pentatomidae) was fed an herbivore Spodoptera
      exigua (Hubner) (Lepidoptera: Noctuidae) larvae from control diet and diets at
      two Se levels (0, 109, and 135 microg/g sodium selenate dry weight added).
      Predators reared on larvae grown on diets with sodium selenate took longer to
      complete each developmental stage and had significantly higher mortality rates.
      Predators achieving the adult stage on Se-containing hosts weighed 20% less than
      those feeding on control larvae. Reduced adult weight of insects has been
      associated with reduced fitness (longevity, egg production, etc.), which would
      have long-term negative impacts on population dynamics. These developmental and
      mortality effects resulted from biotransfer of Se, not biomagnification since the
      trophic transfer factor was less than 1.0 (approximately 0.85). Host larvae in Se
      treatments contained significantly more total Se (9.76 and 13.0 microg/g Se dry
      weight host larvae) than their predators (8.34 and 11 microg/g Se dry weight
      predatory bugs, respectively). Host larvae and predators in the control groups
      did not differ in their Se content. These data demonstrate that Se in the food
      chain may have detrimental population level effects on insects even in the
      absence of biomagnification, given the host contains significantly elevated
      concentrations of selenium.

PMID- 14680331
TI  - Editorial: the unknown environmental tragedy in Sumgayit, Azerbaijan.

PMID- 14680333
TI  - Integrating evolutionary genetics and ecotoxicology: on the correspondence
      between reaction norms and concentration-response curves.

PMID- 14680332
TI  - Chemical contaminants and their effects in fish and wildlife from the industrial
      zone of Sumgayit, Republic of Azerbaijan.
AB  - Sediment from a wetland adjacent to an industrial wastewater treatment plant in
      Sumgayit contained concentrations of total PAHs, total PCBs, aldrin, biphenyl,
      chlordane, DDT, mercury, beta-endosulfan, heptachlor, alpha-hexacyclohexane
      (alpha-HCH), gamma-HCH, and several individual PAH congeners that were elevated
      relative to published sediment quality guidelines. Chemical analyses of tissues
      from European pond turtles (Emys orbicularis) had increased levels of many of the
      same chemicals including aldrin, chlordane, heptachlor, alpha-HCH, total PCBs,
      total PAHs, and mercury, compared to reference turtles. In addition, turtle
      tissues contained elevated levels of DDD, hexachlorobenzene (HCB), and
      pentachlorobenzene that were not elevated in the sediment sample. Some
      differences were observed in contaminant levels between European pond turtles and
      Caspian turtles (Mauremys caspica) taken from the ponds in Sumgayit.
      Salmonella/microsome mutagenicity assays on pond sediments were negative or
      weakly positive. Micronuclei in European pond turtles were statistically
      correlated with tissue levels of mercury, heptachlor, DDD, HCB, and trans
      nonachlor. Microcosm experiments using Russian sturgeon (Acipenser
      gueldenstaedtii) showed a positive dose-response relationship between exposure to
      suspended contaminated pond sediment and acute toxicity. Chemical and biological
      assays used in this study show the industrial area of Sumgayit is heavily
      contaminated with a complex mixture of toxic pollutants. Exposure to contaminated
      sediments produced acute effects in Russian sturgeon, but genotoxic effects
      appear to be slight.

PMID- 14680334
TI  - Gene therapy to develop a genetically engineered cardiac pacemaker.
AB  - While cardiac pacemakers are frequently used for the treatment of
      bradydysrhythmias (from diseases of the cardiac conduction system), their use is
      still limited by complications that can be life-threatening and expensive.
      Genetic engineering approaches offer an opportunity to modulate cellular
      automaticity in a manner that could have significant therapeutic potential. It is
      well known that ventricular myocytes exhibit a more negative diastolic potential
      than do pacemaker cells, in large part because of the inward rectifying potassium
      current/K1 (which pacemaker cells lack). Taking advantage of these intrinsic
      electrophysiological differences, a biological pacemaker has recently been
      developed by Miake et al (Nature 2002; 419:132-133) using adenoviral gene
      transfer approaches. By isolating the gene responsible for/K1 (the Kir2.1 gene),
      mutating it to make it a dysfunctional channel (a dominant-negative), inserting
      the mutated gene into an adenoviral vector, and delivering the virus to the
      hearts of guinea pigs, the investigators were able to successfully convert some
      ventricular myocytes to pacemaker cells. While issues of safety and long-term
      efficacy need to be further established, the results of these experiments provide
      proof of principle that gene transfer offers great promise for treatment of
      electrophysiological disorders including conduction system disease.

PMID- 14680335
TI  - Implantable devices benefit patients with cardiovascular diseases.
AB  - Although major advances have been made in the prevention, diagnosis, and
      treatment of cardiovascular diseases, the prevalence of these diseases in the US
      population is almost 62 million, with almost 8 million having had a myocardial
      infarction and nearly 5 million with a diagnosis of heart failure. Increasingly
      implantable devices have been used to decrease mortality and morbidity in
      patients with coronary heart disease. The dramatic reduction in mortality
      reported in the recent clinical trial of implantable cardioverter defibrillators
      in MADIT II (Multicenter Automatic Defibrillator Trial II) and decrease in
      hospitalizations, improved exercise tolerance, and better quality of life with
      cardiovascular resynchronization therapy reported in MIRACLE (Multicenter InSync
      Randomized Clinical Evaluation) led the American Heart Association to name
      treatment with implantable devices as one of the top 10 research advances for
      2002. This article reviews the pathophysiology of cardiac dysrhythmia in the
      context of either heart failure or low ejection fraction, standard medical
      therapy, results of important clinical trials of implantable cardioverter
      defibrillator and offers suggestions for future directions.

PMID- 14680336
TI  - A refined angioplasty and stenting technique may offer an alternative to carotid
      endarterectomy.
AB  - Strokes are the third leading cause of death in the United States. Carotid artery
      occlusive disease accounts for about 20% to 30% of all strokes. Carotid
      endarterectomy has been the traditional standard treatment for patients with
      significant carotid artery disease. However, surgical therapy is associated with
      significant complications. Carotid angioplasty and stenting offers an attractive
      alternative to surgery. There have been significant advances in this field
      including the use of embolic protection devices. In this article, we review the
      current literature addressing the role of endovascular interventions in the
      management of patients with significant carotid stenosis.

PMID- 14680337
TI  - Estrogen plus progestin therapy: the cardiovascular risks exceed the benefits.
AB  - The surprising results of the Women's Health Initiative (WHI) reported in 2002
      had a profound effect on women as well as health care practitioners. The WHI was
      the largest, randomized clinical trial designed to determine if postmenopausal
      hormone use prevented cardiovascular disease as well as other age-related
      disorders in women. While observational studies suggested that postmenopausal use
      of estrogen could decrease cardiovascular risk by 40% to 50%, the WHI
      demonstrated that use of continuous-combined estrogen plus progestin was not
      cardioprotective and was even associated with increased health risks. The
      estrogen alone trial of the WHI is still in progress, leaving practitioners and
      some women still in a dilemma. This article addresses the WHI in the context of
      other studies and discusses possible reasons for the unexpected results.

PMID- 14680338
TI  - Compliance with acute MI guidelines lowers inpatient mortality.
AB  - Within the last decade, health care providers have seen the emergence of numerous
      patient care guidelines that can be used to prevent or manage specific medical
      conditions. The American College of Cardiology (ACC) and American Heart
      Association (AHA) have issued guidelines for the management of patients with
      acute myocardial infarction (AMI). In November of 2002, at the annual scientific
      session of the AHA, researchers presented the results of the first study to show
      a direct relationship between inpatient mortality and the level of a hospital's
      compliance with these guidelines. It is hoped that this evidence of a reduction
      in AMI patient mortality will provide an incentive for all hospitals to improve
      their adherence to the ACC/AHA AMI guidelines.

PMID- 14680339
TI  - Obesity and heart failure.
AB  - Current statistics on global obesity are staggering. In 2002, the International
      Obesity Task Force estimated that worldwide, nearly 1 billion (6%) people were
      overweight or obese. The American Heart Association's 2002: "Top 10" Research
      Advances for the Treatment of Heart Disease include obesity as a strong and
      independent risk factor for developing heart failure. This article outlines
      national and world statistics, cardiac risk factors, and pathophysiologic
      theories outlining the cellular mechanisms that associate obesity and heart
      failure. Access to guidelines for effective screening, evaluation, and treatment
      of obesity are also provided.

PMID- 14680340
TI  - Treating atrial fibrillation: rhythm control or rate control.
AB  - Atrial fibrillation (AF), a rhythm characterized by disorganized depolarization
      of the atria, is frequently encountered in the clinical setting. This dysrhythmia
      significantly impacts hemodynamics, exercise tolerance, and quality of life. Many
      factors contribute to this complex dysrhythmia, ultimately leading to electrical
      and mechanical remodeling. Rhythm control has been the initial treatment choice
      for AF. However, until recently, differences in outcomes associated with rhythm
      control versus rate control for AF were unknown. Data from recent clinical trials
      suggest that rate control is equivalent to rhythm control in terms of mortality.
      In the rhythm-control group compared to the rate-control group, there was a
      tendency for increased hospitalizations and medication reactions (although these
      differences were not significant). Anticoagulation remains an important component
      of therapy when treating AF, but continues be to inadequately prescribed.
      Further, INRs commonly are not maintained in a therapeutic range. Finally, the
      results of the Atrial Fibrillation Follow-up Investigation of Rhythm Management
      (AFFIRM), Pharmacological Intervention in Atrial Fibrillation (PIAF), and the
      Comparison of Rate Control and Rhythm Control in Patients with Recurrent
      Persistent Atrial Fibrillation (RACE) trials provide guidance in treatment
      strategies for AF.

PMID- 14680341
TI  - Cellular cardiomyoplasty: a new therapeutic approach for regenerating the
      myocardium.
AB  - One of the most promising new therapeutic techniques for the augmentation and
      regeneration of the myocardium is cellular cardiomyoplasty. Reports from animal
      and clinical investigations indicate that the transplant of different cell types,
      such as autologous skeletal myoblasts and adult stem cells, into injured
      myocardium results in the generation of new cardiac myocytes and improvement in
      myocardial performance. Although there is no consensus with regard to the best
      cell type to transplant or the extent of myocardial renewal and regeneration, the
      technique of cardiac cellular myoplasty may become one of the most important
      advancements in the treatment of cardiovascular diseases such as myocardial
      infarction and heart failure.

PMID- 14680342
TI  - Robotically assisted cardiac surgery: minimally invasive techniques to totally
      endoscopic heart surgery.
AB  - Over the past decade, advancements in cardiac surgery occurred secondary to
      improvements in technology and the desire for a less invasive approach to
      operations in general. Minimally invasive cardiac surgery has progressed from
      partial sternotomy incisions to totally endoscopic open-heart procedures with
      robotic-assistance. There are 2 major companies that produce robotic equipment
      for use in cardiac surgery. These companies must undergo Food and Drug
      Association (FDA) mandated clinical trials on each cardiac surgical procedure,
      before it can be approved for public use. The surgeon must demonstrate clinical
      proficiency to operate the robotic equipment per FDA approved company testing.
      The use of computer (robotic) enhancement is well documented for coronary artery
      bypass grafting and selected cardiac valve procedures. Recent advancements are
      now being directed at congenital heart disease. The use of robotic-assisted
      totally endoscopic atrial septal defect closure is a tremendous advancement in
      congenital cardiac surgery. The future of robotic cardiac surgery will hopefully
      expand to cover more advanced valve procedures, congenital heart defects, and
      other procedures once robots are further modified for pediatric use.

PMID- 14680343
TI  - What ALLHAT tells us about treating high-risk patients with hypertension and
      hyperlipidemia.
AB  - Hypertension and hyperlipidemia are potent cardiovascular risk factors. Treatment
      can lower blood pressure and reduce events, but the optimal drug for initial
      hypertension treatment and the benefits of long-term cholesterol reduction on
      clinical outcomes in understudied hypertensive subpopulations were unknown. The
      Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
      (ALLHAT) was a long-term randomized, multicenter study undertaken to address
      these questions. In the hypertension component, 42,448 patients with mild
      moderate hypertension and 1 or more other coronary risk factors were randomized
      to initial therapy with chlorthalidone, or to a newer antihypertensive agent-
      doxazosin (alpha blocker), amlodipine (calcium blocker), or lisinopril
      (angiotensin-converting enzyme inhibitor). The primary combined endpoint was
      coronary heart disease mortality or nonfatal myocardial infarction, with
      secondary endpoints including combinations of mortality, cardiac, and vascular
      complications. By interim analysis, doxazosin was shown inferior to diuretics in
      preventing secondary endpoints, resulting in early termination of this arm. There
      were no differences in primary endpoint frequency in chlorthalidone-amlodipine
      and chlorthalidone-lisinopril comparisons, but both amlodipine and lisinopril
      therapy resulted in more secondary events. In the lipid-lowering trial, 10,355
      patients enrolled in the hypertensive trial with low-density-lipoprotein levels
      100 to 189 mg/dL were randomized to pravastatin or usual care. There was no
      overall difference in the primary endpoint (total mortality) or most secondary
      endpoints, with statin therapy reducing stroke and coronary events modestly but
      nonsignificantly. Subgroup comparisons showed equivalent treatment effects in all
      groups except blacks, who had greater reduction in total coronary events but more
      strokes with pravastatin therapy and more strokes with lisinopril treatment.

PMID- 14680344
TI  - Evaluating resident education.

PMID- 14680345
TI  - The upcoming epidemic of fragility fractures in Canada.

PMID- 14680346
TI  - Steal syndrome complicating upper extremity hemoaccess procedures: incidence and
      risk factors.
AB  - INTRODUCTION: Steal syndrome is a potentially grave complication of upper
      extremity hemoaccess (HA) in patients with renal failure. To determine the
      incidence and risk factors for steal in these patients at the St. Boniface
      Hospital, Winnipeg, a tertiary care centre for vascular surgery and dialysis, we
      reviewed data from patients requiring hemodialysis between September 1986 and
      July 2000. PATIENTS AND METHODS: We excluded all venous catheter and lower
      extremity procedures. There remained 325 upper extremity procedures in 217
      patients. Data were collected from the patients' charts or by interview. First by
      univariate analysis and then by multivariate analysis for independent risk
      factors, we studied the effect on the development of steal of age, sex, race
      diabetes mellitus, hypertension, coronary artery disease or cerebrovascular
      disease, smoking, proximal procedures based on the brachial artery, distal
      procedures based on the radial artery, the use of prosthetic graft material and
      the creation of autologous fistulas. RESULTS: The incidence of steal was 6.2%.
      The significant independent risk factors were diabetes mellitus (odds ratio [OR]
      5.00, 95% confidence interval [CI] 1.39-18.08, p = 0.01) and Aboriginal race (OR
      3.59, 95% CI 1.07-12.04, p = 0.04). An increasing risk for each year of advancing
      age at the time of procedure was suggested but was not significant (OR 1.04, 95%
      CI 1.00-1.09 p = 0.07). CONCLUSIONS: Patients who are diabetic or Aboriginal are
      at increased risk for steal with upper extremity HA procedures. This knowledge
      can guide discussion of dialysis options and informed consent. If upper extremity
      HA procedures are undertaken in patients at risk, they should be closely
      monitored and early intervention applied if necessary.

PMID- 14680348
TI  - Optimal excision margins for primary cutaneous melanoma: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: To determine in patients with localized primary melanoma of the trunk
      or extremities the optimal excision margin that achieves the highest disease-free
      survival and overall survival and the lowest local recurrence rate. DATA SOURCES:
      Trials comparing 2 different excision margins were identified by searching
      MEDLINE from 1966 to May 2002 using the term "melanoma," subheading "surgery,"
      and limiting the search to human studies and randomized controlled trials (RCTs).
      Additional studies were found using the MeSH term "surgical procedures,
      operative," combining with "melanoma," and limiting to human studies. We searched
      EMBASE and the Cochrane Library in May 2002 using similar terminology. No
      language restriction was applied. STUDY SELECTION: We selected studies for the
      overview using the following inclusion criteria: design--an RCT with wide
      excision versus narrower excision (margin width was not specified a priori);
      population--adult patients (> 18 yr) with cutaneous melanoma of the trunk or
      extremities without evidence of metastasis; intervention--surgical excision of
      the primary melanoma; and outcomes--at least 1 of overall survival, disease-free
      survival, local recurrence, wound complications and necessity for skin grafting.
      DATA EXTRACTION: Information was abstracted for each outcome reported in the
      studies, and results were pooled by consensus. Statistical analysis was performed
      using RevMan 4.1 (The Cochrane Collaboration) software program. Relative risk and
      risk difference were reported with 95% confidence intervals. The number needed to
      harm was calculated for the need for skin grafting by taking the inverse of the
      risk difference. DATA SYNTHESIS: Three trials and their follow-up studies met the
      inclusion criteria and included 2087 adults with localized cutaneous melanoma of
      the trunk or extremities. No statistically significant differences were found
      between wide surgical excision (margins ranging from 3-5 cm) and narrower
      surgical excision (margins ranging from 1-2 cm) with respect to mortality,
      disease-free survival or local recurrence rate. CONCLUSIONS: Surgical excision
      margins no more than 2 cm around a melanoma of the trunk or extremities are
      adequate; overall survival, disease-free survival and recurrence rate are not
      adversely affected compared with a wider excision. There is more data to support
      a 2-cm margin than a 1-cm margin as the minimum margin of excision. Surgical
      margins should be no less than 1 cm around the primary melanoma.

PMID- 14680349
TI  - Venting during prophylactic nailing for femoral metastases: current orthopedic
      practice.
AB  - INTRODUCTION: Reamed intramedullary nailing, recommended for impending fracture
      of a femur weakened by bone metastases, causes a rise in intramedullary pressure
      and increases the risk of a fat embolism syndrome. The pressure can be equalized
      by the technique of venting--drilling a hole into the distal cortex of the femur.
      Our objective was to study the current practice of orthopedic surgeons in Ontario
      with respect to venting during prophylactic intramedullary nailing for an
      impending femoral fracture due to bone metastases. METHODS: We mailed a
      questionnaire to all orthopedic surgeons from the Province of Ontario listed in
      the 1999 Canadian Medical Directory or on the Canadian Orthopaedic Association
      membership list, asking if they vent when prophylactically nailing an impending
      pathologic femoral fracture. The responses were modelled as a function of surgeon
      volume and year of graduation. RESULTS: Of the 415 surveys mailed, 223 (54%)
      surgeons responded. Of these, 81% reported having prophylactically treated a
      femoral metastatic lesion during the previous year; 67% treated 1 to 3 metastatic
      lesions and 14% treated more than 3; 19% did not treat a metastatic femoral
      lesion prophylactically. Over two-thirds of surgeons had never considered
      venting, whereas one-third always or sometimes vented the femoral canal. More
      recent graduates were 3 times more likely to vent than earlier (before 1980)
      graduates (odds ratio [OR] = 3.2, 95% confidence interval [CI] 1.6-6.5) as were
      those who treat a greater number of impending fractures (OR = 1.4, 95% CI 1.1
      1.7). CONCLUSIONS: Although there is a theoretical rationale for routine venting,
      there is disagreement among Ontario orthopedic surgeons regarding the use of this
      technique during prophylactic nailing for femoral metastatic lesions. Prospective
      evidence will be required to warrant a change in the standard of care.

PMID- 14680347
TI  - Surgical treatment of incidentally identified pancreatic masses.
AB  - INTRODUCTION: With the improved quality and widespread availability of diagnostic
      abdominal imaging, incidental intra-abdominal lesions (incidentalomas) are being
      increasingly identified. Our objective was to characterize the clinical features
      of asymptomatic patients with incidentally discovered pancreatic lesions and to
      assess the accuracy of preoperative radiologic diagnosis against the final
      histologic diagnosis. METHODS: This cohort study is based on prospectively
      collected data from a surgical pancreatic database. Preoperative imaging of
      patients with pancreatic incidentalomas was retrospectively and independently
      assessed by 2 radiologists blinded to the final histologic diagnosis. Seven
      patients who were asymptomatic and had incidentally discovered pancreatic masses
      underwent complete resection of the mass. The clinical features and patient
      survival data were analyzed. The accuracy of preoperative imaging was assessed by
      comparing the preoperative diagnosis to the final histologic diagnosis. RESULTS:
      Lesions most commonly occurred in females (6 patients) and in the tail or body of
      the pancreas (5 patients). The histologic type of the masses included
      neuroendocrine tumour (3), serous cystadenoma (2), intraductal papillary mucinous
      tumour (1) and papillary cystic and solid tumour (1). Preoperative imaging was
      unreliable in predicting the histologic type of the resected mass. CONCLUSIONS:
      Our findings suggest that preoperative imaging does not always predict the
      surgical histologic type of pancreatic incidentalomas. Unless the diagnosis of
      serous cystadenoma is certain, surgical resection should be considered in low
      risk patients in whom pancreatic masses are found incidentally.

PMID- 14680350
TI  - Could laparoscopic colon and rectal surgery become the standard of care? A review
      and experience with 750 procedures.
AB  - INTRODUCTION: The benefits of the laparoscopic approach to colon and rectal
      surgery do not seem as great as for other laparoscopic procedures. To study this
      further we decided to review the current literature and the 10-year experience of
      a surgical group from university teaching hospitals in Montreal, Quebec and
      Toronto in performing laparoscopic colon and rectal surgery. METHODS: The
      prospectively designed case series comprised all patients having laparoscopic
      colon and rectal surgery. The procedures were carried out by a group of 4
      surgeons between April 1991 and November 2001. We noted intraoperative
      complications, any conversions to open surgery, operating time, postoperative
      complications and postoperative length of hospital stay. RESULTS: The group
      attempted 750 laparoscopic colon and rectal procedures of which 669 were
      completed laparoscopically. Malignant disease was the indication for surgery in
      49.6% of cases. Right hemicolectomy and sigmoid colectomy accounted for 54.5% of
      procedures performed. Intraoperative complications occurred in 8.3%, with 29.0%
      of these resulting in conversion to open surgery. The overall rate of conversion
      to open surgery was 10.8%, most commonly for oncologic concerns. Median operating
      time was 175 minutes for all procedures. Postoperative complications occurred in
      27.5% of procedures completed laparoscopically but were mostly minor wound
      complications. Pulmonary complications occurred in only 1.0%. The anastomotic
      leak rate was 2.5%. The early reoperation rate was 2.4%. Postoperative mortality
      was 2.2%. No port site metastases have yet been detected. The median
      postoperative length of stay was 5 days. CONCLUSIONS: The clinical outcomes of
      laparoscopic colon and rectal surgery in this 10-year experience are consistent
      with numerous cohort studies and randomized clinical trials. Laparoscopic colon
      and rectal surgery in the hands of well-trained surgeons can be performed safely
      with short hospital stay, low analgesic requirements and acceptable complication
      rates compared with historical controls and other reports in the literature.
      Evidence from published randomized clinical trials is emerging that under these
      conditions laparoscopic resection represents the better treatment option for most
      benign conditions, but concerns regarding its appropriateness for malignant
      disease are still to be resolved.

PMID- 14680351
TI  - Cost factors in pediatric trauma.
AB  - INTRODUCTION: There is a lack of information on the cost of treating trauma in
      children in developing countries. Therefore, in the pediatric emergency unit of a
      university hospital in Turkey, we prospectively investigated the cost factors of
      pediatric trauma and attempted to identify cost predictors. METHODS: We prepared
      questionnaires and charts for 91 children (50 boys, 41 girls) admitted with
      multiple trauma to obtain data on age, gender, date and mechanism of injury, site
      of injury, type of the treatment and length of hospital stay. We studied the
      physical findings, Pediatric Trauma Score (PTS), Revised Trauma Score (RETS) and
      pediatric Glasgow Coma Scale (GCS) score, and we totalled all hospital-based
      costs according to Ministry of Health guidelines. RESULTS: The mean (and standard
      deviation [SD]) age of the children was 79.4 (52.3) months. Motor vehicle crashes
      accounted for 45% of the injuries, followed by falls (41%) and bicycle accidents
      (14%). The mean (and SD) total cost of care was US dollar 376.60 (dollar 428.20)
      (range from dollar 20-dollar 1995). The cost associated with motor vehicle
      crashes was higher than that for the other injury types (p < 0.05). Seventeen
      patients required major and 27 patients required minor surgical treatment,
      whereas 44 patients were treated conservatively; 3 died. Forty-eight percent of
      patients were referred from another hospital, and the cost of care of referred
      patients was significantly higher than for those admitted directly (p < 0.001).
      The mean (and SD) duration of hospital stay was 98 (150) hours. Total cost
      correlated directly with the duration of hospital stay and distance of the
      referred hospital or accident scene from our hospital (p < 0.001, r = 0.827 and
      0.374 respectively), but the cost correlated inversely with the PTS, the RETS and
      the pediatric GCS score (p < 0.001, r = -0.339, -0.301 and -0.453 respectively).
      CONCLUSION: Our findings indicate that the cost of pediatric trauma is high and
      may be predicted from admission data and trauma scores.

PMID- 14680352
TI  - Increasing volume of patients at level I trauma centres: is there a need for
      triage modification in elderly patients with injuries of low severity?
AB  - INTRODUCTION: Since the introduction of a regionalized trauma system in Quebec in
      1993, patient loads at level I trauma centres have been increasing gradually. We
      aimed to investigate the type of patient presenting to 4 tertiary trauma centres
      in Quebec, the nature of their injuries and whether there was a need to modify
      triage protocols. METHODS: The study consisted of a review of major trauma
      patients entered into a regional trauma registry between Apr. 7, 1993, and Mar.
      31, 2000. A total of 29 669 patients fulfilled the eligibility criteria. We
      compared patient demographics, injury type and severity and mechanism of injury.
      RESULTS: During the 7 years of the study, there was an increase in the volume and
      presentation of patients injured in falls (p < 0.01), patients with extremity
      injuries (p < 0.01), single injuries (p < 0.01) and injuries to single body
      regions (p < 0.01). Young patients were mostly injured in motor vehicle
      collisions and had multiple injuries of high severity whereas elderly patients
      were mostly injured in falls and experienced isolated extremity injuries of low
      severity. CONCLUSIONS: The proportion of elderly patients injured in falls,
      experiencing isolated extremity injuries of low severity and being treated at
      tertiary trauma centres in Quebec is overwhelmingly high. Revision of pre
      hospital triage protocols should be considered and studied in order to transport
      trauma patients to appropriate facilities.

PMID- 14680353
TI  - Do medical students have the knowledge needed to maximize organ donation rates?
AB  - INTRODUCTION: The chronic shortage of organs for donation could be improved by
      increasing the numbers of potential and actual donors. Physicians can play a key
      role in solving this problem but may miss opportunities because they lack
      knowledge about organ donation to answer questions or concerns. Education of
      physicians early in their careers may lead to better procurement rates for donor
      organs. We carried out a study at Queen's University in Kingston, Ont., to
      determine whether medical students have sufficient knowledge of topics shown to
      affect organ donation rates. METHODS: Medical students from years 1-4 completed a
      self-administered questionnaire. Section 1 tested general knowledge about organ
      donation; section 2 tested the students' ability to identify potential donors;
      and section 3 dealt with the approach to the potential donor's family. Univariate
      predictors of mean test scores were assessed using the t-test. RESULTS: Of 322
      medical students who received the questionnaire, 260 (81%) responded. The mean
      age of the students was 25 years and 54% were men. The mean knowledge score was
      6.7 out of a possible score of 14. Third-year students had the best knowledge
      scores (7.6), followed by fourth- (7.4), second- (6.6) and first-year students
      (5.7). Teaching about organ donation and a student's comfort with approaching a
      family for organ donation were also predictive of higher knowledge scores. There
      was no correlation between knowledge score and age, gender or whether the student
      was carrying a signed donor card. Knowledge scores were low in all 3 sections.
      Thirty-six percent of students did not know that brain death means that the
      patient is dead rather than in a coma. Half the medical students believed that
      people of certain religious groups should not be approached about organ donation.
      CONCLUSIONS: Medical students possess limited knowledge about organ donation
      topics important for maximizing procurement rates. A teaching intervention
      designed to target these shortcomings may be beneficial.

PMID- 14680355
TI  - Surgical images: musculoskeletal acetabular cartilage delamination demonstrated
      by magnetic resonance arthrography: inverted "Oreo" cookie sign.

PMID- 14680354
TI  - The Canadian Urology Fair: a model for minimizing the financial and academic
      costs of the residency selection process.
AB  - INTRODUCTION: In 1994, the Canadian urology residency training programs designed
      the "Canadian Urology Fair"--a single-site (Toronto, Ont.), 1-day fair to conduct
      the personal interview portion of the residency selection process. The objective
      of the current study was to evaluate the success of the Urology Fair in achieving
      its original goals of decreasing the financial burden and minimizing time away
      from medical training for applicants and faculty. METHODS: Both candidates and
      Canadian urology training programs were surveyed regarding the financial and
      academic costs (days absent) of attending the 2001 Urology Fair. Data from the
      2001 Canadian Resident Matching Service (CaRMS) was used to compare the financial
      and academic costs of attending personal interviews incurred by candidates
      declaring urology as their first-choice discipline to candidates interviewing
      with other surgical specialties throughout Canada. RESULTS: Financial costs
      incurred by candidates to attend the Urology Fair (mean Can dollar 367) were
      significantly lower than candidates' estimated costs of attending on-site
      interviews at the individual programs (mean Can dollar 2065). The financial costs
      of attending personal interviews by CaRMS applicants declaring urology as their
      first-choice discipline (mean Can dollar 2002) were significantly lower than the
      costs incurred by applicants interviewing with other surgical disciplines (mean
      Can dollar 2744). Financial costs to urology programs attending the fair (mean
      Can dollar 1931) were not significantly greater than the programs' estimated
      costs of conducting on-site interviews at their respective program locations
      (mean Can dollar 1825). Days absent from medical school to attend interviews were
      significantly lower among CaRMS applicants declaring urology as their first
      choice discipline (3 d) compared with applicants who interviewed with other
      surgical specialties (9.1 d). CONCLUSION: The Canadian Urology Fair represents an
      innovative and efficient method for residency programs to conduct the personal
      interview portion of the residency selection process and should serve as a model
      for making the interview process less expensive and time-consuming for both
      candidates and faculty.

PMID- 14680356
TI  - Radiology for the surgeon. Soft-tissue case 53. Postgastrectomy jejunogastric
      intussusception.

PMID- 14680357
TI  - Canadian Association of General Surgeons Evidence Based Reviews in Surgery. 8.
      Efficacy and safety of recombinant human activated protein C for severe sepsis.

PMID- 14680358
TI  - Giant cell reparative granuloma of the hand: case report and review of giant cell
      lesions of hands and feet.

PMID- 14680359
TI  - Giant adrenal pseudocyst mimicking a malignant lesion.

PMID- 14680360
TI  - Frequency of NY-ESO-1 and LAGE-1 expression in bladder cancer and evidence of a
      new NY-ESO-1 T-cell epitope in a patient with bladder cancer.
AB  - Cancer-testis (CT) antigens are ideal vaccine targets since their expression is
      restricted in adult tissues to testicular germ cells and a subset of cancers. The
      frequency of expression in transitional cell carcinomas (TCCs) of NY-ESO-1, the
      most immunogenic CT antigen to date, and its closely related gene LAGE-1 was
      studied. NY-ESO-1 and LAGE-1 antigen expression were found to occur frequently in
      high-grade TCC tumors. On an MSKCC IRB-approved protocol, 68 patient specimens
      were collected prospectively at the time of transurethral resection or
      cystectomy, of which 43 were read pathologically as high-grade tumors (pCIS,
      pTaG3, pT1, pT2, pT3, and pT4), 8 as low-grade tumors (pTaG1, pTaG2), and 17 as
      disease-free samples. These 68 samples were analyzed by immunohistochemistry
      (IHC) and/or RT-PCR. There were also an additional 53 paraffin-embedded specimens
      studied retrospectively by IHC, of which 39 were high-grade tumors and 14 were
      low-grade tumors. Cumulatively, our data indicate that NY-ESO-1 and/or LAGE-1 are
      expressed in 39/82 (48%) high-grade TCC and 3/22 (14%) low-grade TCC samples when
      analyzed by RT-PCR and/or IHC. Immunological assessment of these patients' sera
      identified one patient, whose tumor homogeneously expressed NY-ESO-1, which had
      detectable antibodies against NY-ESO-1 and LAGE-1. Further analysis of this
      patient, who remains clinically without evidence of disease 24 months after
      cystectomy for high-grade pT4 disease, revealed T-cell immunity against NY-ESO-1.
      This patient's T-cell response was determined to be specific for a new NY-ESO-1
      epitope, p94-102, in the context of HLA-B35.

PMID- 14680362
TI  - N-glucuronidation of trans-3'-hydroxycotinine by human liver microsomes.
AB  - trans-3'-Hydroxycotinine is the major nicotine metabolite excreted in the urine
      of smokers and other tobacco or nicotine users. On average, about 30% of the
      trans-3'-hydroxycotinine in urine is present as a glucuronide conjugate. The O
      glucuronide of trans-3'-hydroxycotinine has been isolated from smokers urine and
      appears to be the major glucuronide conjugate of trans-3'-hydroxycotinine in
      urine. However, nicotine and cotinine are both glucuronidated at the nitrogen
      atom of the pyridine ring. We report here that human liver microsomes catalyze
      both the N-glucuronidation and the O-glucuronidation of trans-3'-hydroxycotinine.
      The N-glucuronide was purified by HPLC, and its structure was confirmed by NMR.
      Both N- and O-glucuronidation of trans-3'-hydroxycotinine were detected in 13 of
      15 human liver microsome samples. The ratio of N-glucuronidation to O
      glucuronidation was between 0.4 and 2.7. One sample only catalyzed N
      glucuronidation, and one sample did not catalyze either reaction. The rates of N
      glucuronidation varied more than 6-fold from 6 to 38.9 pmol/min/mg protein; rates
      of O-glucuronidation ranged from 2.8 to 23.4 pmol/min/mg protein. The rate of
      trans-3'-hydroxycotinine N-glucuronidation by human liver microsomes correlated
      well with both the rate of nicotine and the rate of cotinine N-glucuronidation.
      trans-3'-Hydroxycotinine O-glucuronidation correlated with neither nicotine nor
      cotinine N-glucuronidation. These results suggest that the same enzyme(s) that
      catalyzes the N-glucuronidation of nicotine and cotinine may also catalyze the N
      glucuronidation of trans-3'-hydroxycotinine in the human liver but that a
      separate enzyme catalyzes trans-3'-hydroxycotinine O-glucuronidation.

PMID- 14680363
TI  - Polymorphisms in the human monomethylarsonic acid (MMA V) reductase/hGSTO1 gene
      and changes in urinary arsenic profiles.
AB  - Large interindividual variability in urinary arsenic profiles, following chronic
      inorganic arsenic exposure, is well-known in humans. To understand this
      variability, we studied the relationship between polymorphisms in the gene for
      human monomethylarsonic acid (MMA(V)) reductase/hGSTO1 and the urinary arsenic
      profiles of individuals chronically exposed to arsenic in their drinking water.
      To ensure that we did not overlook rare polymorphisms, not included in the public
      databases, we amplified and sequenced all six exons of the gene and their
      flanking regions, using DNA isolated from peripheral blood samples of 75
      subjects, living in the vicinity of Torreon, Mexico. Four groups, based on the
      levels of arsenic (9-100 microg/L) in their drinking water, were studied. We
      identified six novel polymorphisms and two reported previously. The novel
      polymorphisms were a three base pair deletion (delGGC) in the first intron; a G >
      C transversion, leading to a serine-to-cysteine substitution at amino acid 86; a
      G > T transversion and a A > T transversion in intron 5; a G > A transition
      resulting in glutamate-to-lysine substitution in amino acid 208; and a C > T
      transition producing an alanine-to-valine substitution in amino acid 236. Two
      subjects displayed significant differences in patterns of urinary arsenic; they
      had increased levels of urinary inorganic arsenic and reduced levels of
      methylated urinary arsenic species as compared to the rest of the study
      population. These two subjects had the same unique polymorphisms in hGSTO1 in
      that they were heterozygous for E155del and Glu208Lys. The identified SNPs may be
      one of the reasons for the large interindividual variability in the response of
      humans to chronic inorganic arsenic exposure. The findings suggest the need for
      further studies to identify unambiguously specific polymorphisms that may account
      for interindividual variability in the human response to chronic inorganic
      arsenic exposure.

PMID- 14680364
TI  - Tolerogenic role of Kupffer cells in allergic reactions.
AB  - Drug-induced allergic reactions (DIARs), including allergic hepatitis, cutaneous
      reactions, and blood dyscrasias, are unpredictable and can be life threatening.
      Although current studies suggest that DIARs are caused by immunogenic drug
      protein adducts, it remains unclear what factors determine the susceptibility to
      DIARs. We hypothesized that most individuals may be resistant to DIARs in part
      because they become immunologically tolerant to drug-protein adducts in the
      liver, an organ with tolerogenic properties. Because animal models of DIARs are
      elusive, we tested this hypothesis using a murine model of 2,4
      dinitrochlorobenzene (DNCB)-induced delayed type hypersensitivity reaction that
      is mediated by immunogenic 2,4-dinitrophenylated (DNP)-protein adducts.
      Intravenous pretreatment of mice with DNP-BSA led to its accumulation in hepatic
      Kupffer cells (KC) and induced immunological tolerance to subsequent DNCB
      sensitization. Tolerance could be abrogated by prior depletion of KC or induced
      in naive mice by transferring a T cell-depleted, KC-enriched fraction of liver
      nonparenchymal cells from mice tolerized 1 month earlier by DNP-BSA pretreatment.
      These findings implicate KC as a primary and sustained inducer of tolerance
      against DNP-protein adducts and suggest a similar role in modulating allergic
      reactions against drug-protein adducts. Perhaps genetic and/or environmental
      factors affecting the activities of these cells may play a role in determining
      individual susceptibility to DIARs.

PMID- 14680365
TI  - Resistance to acute silicosis in senescent rats: role of alveolar macrophages.
AB  - We have previously demonstrated in alveolar macrophages that aging is associated
      with a decline in lipopolysaccharide-induced tumor necrosis factor-alpha
      production. The purpose of the present study was to investigate the
      immunotoxicological consequences of this defective activation in an experimental
      model of acute silicosis. Young (3 months old) and old (>18 months old) rats were
      intratracheally instilled with silica or saline as control. In young animals, as
      expected, silica induced a significant increase in bronchoalveolar lavage fluid
      of tumor necrosis factor-alpha, lactate dehydrogenase, and cell numbers, which
      correlated with increased collagen deposition and silicotic nodule formations. On
      the contrary, in old rats, no changes in bronchoalveolar lavage fluid or lung
      parameters were observed, indicating that senescent rats are resistant to the
      acute effects of silica. These in vivo results were confirmed in vitro, where
      silica-induced tumor necrosis factor-alpha release was drastically reduced in
      alveolar macrophages obtained from old animals. This could be explained with a
      defective protein kinase C betaII translocation in aged macrophages, due to
      decreased expression of its anchoring protein RACK-1. Furthermore, a decrease in
      FAS-L expression and silica-induced apoptosis in old macrophages was observed,
      supporting the idea that age-associated alterations in signal transduction
      pathways contribute to decreased sensitivity to silica-induced acute lung
      fibrosis in old animals.

PMID- 14680366
TI  - DNA lesions derived from the site selective oxidation of Guanine by carbonate
      radical anions.
AB  - Carbonate radical anions are potentially important oxidants of nucleic acids in
      physiological environments. However, the mechanisms of action are poorly
      understood, and the end products of oxidation of DNA by carbonate radicals have
      not been characterized. These oxidation pathways were explored in this work,
      starting from the laser pulse-induced generation of the primary radical species
      to the identification of the stable oxidative modifications (lesions). The
      cascade of events was initiated by utilizing 308 nm XeCl excimer laser pulses to
      generate carbonate radical anions on submicrosecond time scales. This laser flash
      photolysis method involved the photodissociation of persulfate to sulfate radical
      anions and the one electron oxidation of bicarbonate anions by the sulfate
      radicals to yield the carbonate radical anions. The latter were monitored by
      their characteristic transient absorption band at 600 nm. The rate constants of
      reactions of carbonate radicals with oligonucleotides increase in the ascending
      order: 5'-d(CCATCCTACC) [(5.7 +/- 0.6) x 10(6) M(-)(1) s(-)(1)] < 5'
      d(TATAACGTTATA), self-complementary duplex [(1.4 +/- 0.2) x 10(7) M(-)(1) s(
      )(1)] < 5'-d(CCATCGCTACC [(2.4 +/- 0.3) x 10(7) M(-)(1) s(-)(1)] < 5'-d(CCATC[8
      oxo-G]CTACC) [(3.2 +/- 0.4) x 10(8) M(-)(1) s(-)(1)], where 8-oxo-G is 8-oxo-7,8
      dihydroguanine, the product of a two electron oxidation of guanine. This
      remarkable enhancement of the rate constants is correlated with the presence of
      either G or 8-oxo-G bases in the oligonucleotides. The rate constant for the
      oxidation of G in a single-stranded oligonuclotide is faster by a factor of
      approximately 2 than in the double-stranded form. The site selective oxidation of
      G and 8-oxo-G residues by carbonate radicals results in the formation of unique
      end products, the diastereomeric spiroiminodihydantoin (Sp) lesions, the products
      of a four electron oxidation of guanine. These lesions, formed in high yields (40
      60%), were isolated by reversed phase HPLC and identified by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry. These assignments
      were supported by the characteristic circular dichroism spectra of opposite signs
      of the two lesions. The oxidation of guanine to Sp diastereomers occurs, at least
      in part, via the formation of 8-oxo-G lesions as intermediates. The Sp lesions
      can be considered as the terminal products of the oxidation of G and 8-oxo-G in
      DNA by carbonate radical anions. The mechanistic aspects and biological
      implications of these site selective reactions in DNA initiated by carbonate
      radicals are discussed.

PMID- 14680367
TI  - Sequence specificity of DNA alkylation by the antitumor natural product
      leinamycin.
AB  - Reaction with thiol converts the antitumor natural product leinamycin to an
      episulfonium ion that alkylates the N(7)-position of guanine residues in double
      stranded DNA. The sequence specificity for DNA alkylation by this structurally
      novel compound has not previously been examined. It is reported here that
      leinamycin shows significant (>10-fold) preferences for alkylation at the 5'-G in
      5'-GG and 5'-GT sequences. The sequence preferences for activated leinamycin are
      significantly different from that observed for the structurally simple
      episulfonium ion generated from 2-chloroethyl ethyl sulfide. DNA alkylation by
      activated leinamycin is inhibited by addition of salt (100 mM NaClO(4)), although
      the degree of inhibition is somewhat less than that seen for 2-chloroethyl ethyl
      sulfide. This result suggests that electrostatic interactions between the
      activated leinamycin and the N(7)-position of guanine residues facilitate
      efficient DNA alkylation. However, the observed sequence preferences for DNA
      alkylation by activated leinamycin do not correlate strongly with calculated
      sequence-dependent variations in the molecular electrostatic potential at the
      N(7)-atom of guanine residues in duplex DNA. Thus, electrostatic interactions
      between activated leinamycin and DNA do not appear to be the primary determinant
      for sequence specificity. Rather, the results suggest that sequence-specific
      noncovalent interactions of leinamycin with the DNA double helix on the 3'-side
      of the alkylated guanine residue play a major role in determining the preferred
      alkylation sites. Consistent with the notion that noncovalent binding plays an
      important role in DNA alkylation by leinamycin, experiments with 2'
      deoxyoligonucleotide substrates confirm that the natural product does not
      alkylate single-stranded DNA under conditions where duplex DNA is efficiently
      alkylated.

PMID- 14680368
TI  - Reduction of nilutamide by NO synthases: implications for the adverse effects of
      this nitroaromatic antiandrogen drug.
AB  - Nitric oxide synthases (NOSs) are flavohemeproteins that catalyze the oxidation
      of l-arginine to l-citrulline with formation of the widespread signal molecule
      NO. Beside their fundamental role in NO biosynthesis, these enzymes are also
      involved in the formation of reactive oxygen species and in the interactions with
      some xenobiotic compounds. Nilutamide is a nonsteroidal antiandrogen that behaves
      as a competitive antagonist of the androgen receptors and is proposed in the
      treatment of metastatic prostatic carcinoma. However, therapeutic effects of
      nilutamide are overshadowed by the occurrence of several adverse reactions
      mediated by toxic mechanism(s), which remain(s) poorly investigated. Here, we
      studied the interaction of NOSs with nilutamide. Our results show that the
      purified recombinant neuronal NOS reduced the nitroaromatic nilutamide to the
      corresponding hydroxylamine. The reduction of nilutamide catalyzed by neuronal
      NOS proceeded with intermediate formation of a nitro anion free radical easily
      observed by EPR, was insensitive to the addition of the usual heme ligands and l
      arginine analogues, but strongly inhibited by O(2) and a flavin/NADPH binding
      inhibitor. Involvement of the reductase domain of nNOS in the reduction of
      nilutamide was confirmed by (i) the ability of the isolated reductase domain of
      nNOS to catalyze the reaction and (ii) the stimulating effect of
      Ca(2+)/calmodulin on the accumulation of hydroxylamine and nitro anion radical.
      In a similar manner, the recombinant inducible and endothelial NOS isoforms also
      displayed nitroreductase activity, albeit with lower yields. The selective
      reduction of nilutamide to its hydroxylamino derivative by the NOSs could explain
      some of the toxic effects of this drug.

PMID- 14680369
TI  - The octapeptidic end of the C-terminal tail of histone H2A is cleaved off in
      cells exposed to carcinogenic nickel(II).
AB  - We have demonstrated previously that Ni(II) binds to the C-terminal -TESHHKAKGK
      motif of isolated bovine histone H2A. At physiological pH, the bound Ni(II)
      assists in hydrolysis of the E-S peptide bond in this motif that results in a
      cleavage of the terminal octapeptide SHHKAKGK off the histone's C-tail. To test
      if the hydrolysis could also occur in living cells, we cultured CHO (Chinese
      hamster ovary), NRK-52 (rat renal tubular epithelium), and HPL1D (human lung
      epithelium) cells with 0.1-1 mM Ni(II) for 3-7 days. As found by gel
      electrophoresis, Western blotting, and liquid chromatography/mass spectrometry,
      histones extracted from the cells contained a new fraction of histone H2A lacking
      the terminal octapeptide (q-H2A). The abundance of q-H2A increased with Ni(II)
      concentration and exposure time. It can be anticipated that the truncation of
      histone H2A may alter chromatin structure and affect gene expression. The present
      results provide evidence for novel mechanisms of epigenetic effects of Ni(II)
      that may be involved in nickel toxicity and carcinogenesis.

PMID- 14680370
TI  - Analysis of 3'-phosphoglycolaldehyde residues in oxidized DNA by gas
      chromatography/negative chemical ionization/mass spectrometry.
AB  - Deoxyribose oxidation in DNA represents a biologically important facet of
      oxidative DNA damage that gives rise to protein-DNA cross-links and base adducts.
      Toward the goal of quantifying deoxyribose oxidation chemistry in cells, we
      report a method for the quantification of 3'-phosphoglycolaldehyde (PGA)
      residues, which likely arise from 3'-oxidation of deoxyribose in DNA. The method
      exploits the aldehyde moiety in PGA by derivatization as a stable oxime with
      pentafluorobenzylhydroxylamine, followed by solvent extraction and gas
      chromatography/negative chemical ionization/mass spectrometry. A stable
      isotopically labeled [(13)C(2)]PGA was synthesized and used as an internal
      standard. The assay showed a linear response over the range of 30 fmol to 300
      pmol, and its precision was verified by analysis of a synthetic, PGA-containing
      oligodeoxynucleotide. The limit of detection in the presence of DNA was 30 fmol
      per sample, corresponding to two molecules of PGA in 10(6) nucleotides for 170
      microg of DNA. Samples were exposed to 0-100 Gy of (60)Co gamma-radiation, which
      resulted in a linear dose-response of 1.5 PGA residues per 10(6) nucleotides per
      Gy and a radiation chemical yield (G-value) of 0.0016 micromol/J. When compared
      to the total quantity of deoxyribose oxidation occurring under the same
      conditions (141 oxidation events per 10(6) nucleotides per Gy; determined by
      plasmid topoisomer analysis), PGA formation occurs in 1% of deoxyribose oxidation
      events. This small fraction is consistent with current models of limited solvent
      accessibility of the 3'-position of deoxyribose, although partitioning of 3'
      chemistry could lead to other damage products that would increase the fraction of
      oxidation at this site in deoxyribose.

PMID- 14680371
TI  - Predicting the genotoxicity of polycyclic aromatic compounds from molecular
      structure with different classifiers.
AB  - Classification models were developed to provide accurate prediction of
      genotoxicity of 277 polycyclic aromatic compounds (PACs) directly from their
      molecular structures. Numerical descriptors encoding the topological, geometric,
      electronic, and polar surface area properties of the compounds were calculated to
      represent the structural information. Each compound's genotoxicity was
      represented with IMAX (maximal SOS induction factor) values measured by the SOS
      Chromotest in the presence and absence of S9 rat liver homogenate. The compounds'
      class identity was determined by a cutoff IMAX value of 1.25-compounds with IMAX
      > 1.25 in either test were classified as genotoxic, and the ones with IMAX < or =
      1.25 were nongenotoxic. Several binary classification models were generated to
      predict genotoxicity: k-nearest neighbor (k-NN), linear discriminant analysis,
      and probabilistic neural network. The study showed k-NN to provide the highest
      predictive ability among the three classifiers with a training set classification
      rate of 93.5%. A consensus model was also developed that incorporated the three
      classifiers and correctly predicted 81.2% of the 277 compounds. It also provided
      a higher prediction rate on the genotoxic class than any other single model.

PMID- 14680372
TI  - Metabolism of the polynuclear sulfur heterocycle benzo[b]phenanthro[2,3
      d]thiophene by rodent liver microsomes: evidence for multiple pathways in the
      bioactivation of benzo[b]phenanthro[2,3-d]thiophene.
AB  - Benzo[b]phenanthro[2,3-d]thiophene (BPT), a thia analogue of
      dibenz[a,h]anthracene (DBA), is a carcinogenic environmental pollutant. We have
      examined the metabolism of BPT by rodent liver microsomes to investigate the
      mechanism by which BPT produces mutagenic and carcinogenic effects. Both rat and
      mouse liver microsomes biotransformed [G-(3)H]BPT to various metabolites
      including BPT 3,4-diol and BPT sulfoxide, which are significantly more mutagenic
      than the parent compound. Liver microsomes from both control mice and rats
      metabolize BPT at similar rates. Treatment of mice with P450 inducers DBA, 3
      methylcholanthrene (3-MC), Aroclor 1254, and phenobarbital enhanced the rate of
      metabolism of BPT by 74-, 28-, 77-, and 6-fold, respectively. In comparison, the
      treatment of rats with DBA and 3-MC increased the rate of metabolism of BPT by 22
      and 34-fold, respectively, suggesting that P450 enzymes responsible for the
      metabolism of BPT are enhanced to different extents in rats and mice by a similar
      class of compounds. In general, the liver microsomes from mice treated with DBA
      or 3-MC were more active than those from similarly treated rats in metabolizing
      BPT to its 3,4-diol, a precursor to the bay-region diol epoxide of BPT. BPT
      sulfone was a minor metabolite (if formed) in all cases. The liver microsomes
      from rats treated with DBA or 3-MC or from mice treated with PB produced a
      significant proportion of BPT sulfoxide (12-41%). In contrast, the liver
      microsomes from DBA- or 3-MC-treated mice formed BPT sulfoxide as a minor
      metabolite (<2%). These studies indicate that cytochrome P450 enzymes induced by
      PAHs (e.g., P450 1A1 and P450 1B1) and by PB (e.g., P450 2B1, 3A1, and/or 3A2)
      are involved in the metabolism of BPT to mutagenic BPT 3,4-diol and BPT
      sulfoxide, providing evidence for the first time that BPT and possibly other thia
      PAHs are metabolically activated via the formation of both the dihydrodiol (and
      subsequently diol epoxide) and the sulfoxide.

PMID- 14680373
TI  - Carnosine inhibits (E)-4-hydroxy-2-nonenal-induced protein cross-linking:
      structural characterization of carnosine-HNE adducts.
AB  - (E)-4-Hydroxy-2-nonenal (HNE) is a highly cytotoxic aldehyde generated during
      peroxidation of lipids, which induces modification and aggregation of low-density
      lipoproteins and has been found to elicit covalent cross-linking of proteins.
      Carnosine was previously shown to trap HNE. Results presented here provide
      evidence that by trapping HNE in stable covalent adducts, carnosine can inhibit
      HNE-induced protein cross-linking. This trapping effect may be augmented by
      carnosine-chelating trace transition metal ions that promote oxidative HNE
      induced cross-linking. Adducts formed in the reaction of HNE with carnosine have
      been isolated and structurally characterized. The main carnosine-HNE adduct is
      shown to be a 13-member cyclic adduct formed through initial Schiff base
      formation followed by conjugate addition of the imidazole group.

PMID- 14680374
TI  - A novel lipid hydroperoxide-derived modification to arginine.
AB  - The guanidine group present in the amino acid arginine was found to react with
      the lipid hydroperoxide-derived bifunctional electrophile, 4-oxo-2-nonenal. The
      reaction between N(alpha)-tert-butoxycarbony-l-arginine and 4-oxo-2-nonenal
      resulted in the formation of an adduct (adduct A) that subsequently dehydrated on
      heating to adduct B. Liquid chromatography/mass spectrometry and nuclear magnetic
      resonance spectroscopy were used to assign the structure of adduct B as
      (N(delta),N(omega)(')-etheno-2'-heptanon-2' '-one)-N(alpha)-t-Boc-arginine. The
      reaction proceeded from initial reaction of the primary N(omega)-amino group at
      the C-1 aldehyde of 4-oxo-2-nonenal. Subsequently, an intramolecular Michael
      addition of a secondary N(delta)-amino group occurring at C-3 resulted in
      formation of the cyclic carbinolamine adduct A. Dehydration and rearrangement of
      the exocyclic imine resulted in the formation of adduct B, which contained a
      stable imidazole ring. The tetra peptide LRDE reacted with 4-oxo-2-nonenal
      primarily at arginine rather than at the amino terminus. This suggests that
      arginine-containing proteins can react with lipid hydroperoxide-derived 4-oxo-2
      nonenal to form a novel imidazole modification.

PMID- 14680375
TI  - Identification and characterization of a series of nucleoside adducts formed by
      the reaction of 2'-deoxyguanosine and 1,2,3,4-diepoxybutane under physiological
      conditions.
AB  - The carcinogenicity of 1,3-butadiene (BD) has been attributed to its in vivo
      metabolites, 3,4-epoxy-1-butene (EB) and 1,2,3,4-diepoxybutane (DEB). In this
      study, DEB was demonstrated to react with 2'-deoxyguanosine (dG) under in vitro
      physiological conditions (pH 7.4, 37 degrees C) to yield several pairs of
      diastereomeric adducts, including N-(2-hydroxy-1-oxiranylethyl)-2'-deoxyguanosine
      (P4-1 and P4-2), 7,8-dihydroxy-3-(2-deoxy-beta-d-erythro-pentofuranosyl)
      3,5,6,7,8,9-hexahydro-1,3-diazepino[1,2-a]purin-11(11H)one (P6), 1-(2-hydroxy-2
      oxiranylethyl)-2'-deoxyguanosine (P8 and P9), 1-[3-chloro-2-hydroxy-1
      (hydroxymethyl)propyl]-2'-deoxyguanosine (1AP9 and 2AP9), and 4,8-dihydroxy-1-(2
      deoxy-beta-d-erythro-pentofuranosyl)-9-hydroxymethyl-6,7,8,9-tetrahydro-1H
      pyrimido[2,1-b]purinium ion (1BP4 and 2BP4). The 7-alkylation dG adducts (P5 and
      P5') were not characterized directly by NMR spectrometry because of their
      instability. However, their formula weights were determined to be 354, and their
      acid hydrolysis products were characterized as 2-amino-7-(3-chloro-2,4
      dihydroxybutyl)-1,7-dihydro-6H-purin-6-one (H3), consistent with the structures
      of P5 and P5' being diastereomers of 6-oxo-2-amino-9-(2-deoxy-beta-d-erythro
      pentofuranosyl)-7-(2-hydroxy-2-oxiranylethyl)-6,9-dihydro-1H-purinium ion. Time
      course experiments indicated that alkaline pH and/or high DEB:dG molar ratios
      made the reactions faster without changing the adduct profile. The adducts were
      detected in the following chronological order: 7- (P5 and P5'), 1- (P8 and P9),
      N(2)- (P4-1 and P4-2), and P6. Whereas P4-1, P4-2, and P6 appeared stable during
      the courses of the reactions, P5, P5', P8, and P9 were labile and completely
      decomposed by the time dG was fully consumed. These results may contribute to a
      better understanding of the chemical reactivity and strong mutagenicity and
      carcinogenicity of DEB.

PMID- 14680376
TI  - The N2-ethylguanine and the O6-ethyl- and O6-methylguanine lesions in DNA:
      contrasting responses from the "bypass" DNA polymerase eta and the replicative
      DNA polymerase alpha.
AB  - The effects of N(2)-ethylGua, O(6)-ethylGua, and O(6)-methylGua adducts in
      template DNA on polymerization by mammalian DNA polymerases alpha and eta have
      been investigated. The N(2)-ethylGua adduct blocks polymerization by the
      replicative DNA polymerase alpha to a much greater extent than does the O(6)
      ethyl- or the O(6)-methylGua adducts. The DNA polymerase eta efficiently and
      accurately bypasses the N(2)-ethylGua lesion but like DNA polymerase alpha is
      similarly blocked by the O(6)-ethyl- or the O(6)-methylGua adducts. A steady
      state kinetic analysis of nucleotide insertion opposite the N(2)-ethylGua and the
      O(6)-ethylGua adducts by the DNA polymerases alpha and eta and extension from 3'
      termini positioned opposite these adducts was performed to measure the efficiency
      and the accuracy of DNA synthesis past these lesions. This analysis showed that
      insertion of Cyt opposite the N(2)-ethylGua adduct by DNA polymerase alpha is
      approximately 10(4)-fold less efficient than insertion of Cyt opposite an
      unadducted Gua residue at the same position. Extension from the N(2)-ethylGua:Cyt
      3'-terminus by DNA polymerase alpha is approximately 10(3)-fold less efficient
      than extension from a Cyt opposite the unadducted Gua. Insertion of Cyt opposite
      the N(2)-ethylGua lesion by the DNA polymerase eta is about 370-fold more
      efficient than by the DNA polymerase alpha, and extension from the N(2)
      ethylGua:Cyt 3'-terminus by the DNA polymerase eta is about 3-fold more efficient
      than by the DNA polymerase alpha. Furthermore, the DNA polymerase eta preferably
      inserts the correct nucleotide Cyt opposite the N(2)-ethylGua lesion with nearly
      the same level of accuracy as opposite an unadducted Gua, thus minimizing the
      mutagentic potential of this lesion. This result contrasts with the relatively
      high misincorporation efficiency of Thy opposite the O(6)-ethylGua adduct by the
      DNA polymerases alpha and eta. In reactions containing both DNA polymerases alpha
      and eta, synthesis past the N(2)-ethylGua adduct is detected to permit completed
      replication of the adducted oligonucleotide template. These results suggest that
      accurate replication past the N(2)-ethylGua adduct might be facilitated in cells
      by pausing of replication catalyzed by DNA polymerase alpha and lesion bypass
      catalyzed by DNA polymerase eta.

PMID- 14680377
TI  - Biological activity of inorganic arsenic and antimony reflects oxidation state in
      cultured human keratinocytes.
AB  - Sodium arsenite is much more potent than sodium arsenate in producing adverse
      effects in animals and in cultured cells. Although arsenate may exhibit toxicity
      as a phosphate analogue, its potency in vivo appears to be enhanced by reduction
      to arsenite. To understand the relative importance of this reduction, which is
      critical in evaluating the responsiveness of cell culture models to the different
      oxidation states and thus to elucidating the mechanism of arsenic action, present
      work has correlated the extent of reduction with biological activity in human
      keratinocytes. The results show that at biologically relevant concentrations,
      arsenate reduction to appreciable levels required several days, helping
      rationalize a previous empirical observation that it was approximately one-third
      as potent as arsenite. The relatively low conversion rate also emphasizes a
      limitation of culture; arsenate was nearly as efficacious as arsenite, but the
      time required for it to reach maximal effect exceeded ordinary medium change
      intervals. In keratinocytes, an important role for purine nucleoside
      phosphorylase in the reduction could not be demonstrated, indicating that another
      pathway is dominant in this cell type. Methylation of inorganic arsenic, uptake
      of methylated forms, and their reduction were all very slow. These findings
      suggest that the reduced methylated forms have only a small contribution to skin
      carcinogenesis unless they are supplied through the circulation. In parallel
      experiments, trivalent antimony was similar to arsenite in potency and efficacy,
      whereas pentavalent antimony was virtually without biological effect. Conversion
      of antimony in the pentavalent to the trivalent oxidation state was not
      detectable in keratinocytes. These findings emphasize the importance of
      intracellular reduction of the metalloids for biological effects.

PMID- 14680378
TI  - Phosphatidylethanolamine modification by oxidative stress product 4,5(E)-epoxy
      2(E)-heptenal.
AB  - Phosphatidylethanolamine and ethanolamine were incubated with 4,5(E)-epoxy-2(E)
      heptenal to analyze the changes produced in amino phospholipids as a consequence
      of their reaction with this lipid oxidation product. The reactions, which were
      followed by GC/MS or HPLC/MS, produced in a first step the corresponding imines,
      which later evolved into two main products. These products, which were isolated
      and characterized by (1)H and (13)C NMR and mass spectrometry, resulted in the
      corresponding phosphatidylethanolpyrroles (PEPs) and phosphatidylethanol-2-(1
      hydroxypropyl)pyrroles (PEHPs). PEPs were relatively stable, but PEHPs
      polymerized spontaneously. This polymerization, which was followed in 4,5(E)
      epoxy-2(E)-heptenal/ethanolamine incubations with the detection of the
      corresponding dimers and trimers, was related to the brown color and fluorescence
      development produced. In addition, when hydroxyalkylpyrroles were incubated in
      the presence of single pyrroles, mixed polymers of the two pyrroles were
      obtained, and these polymers were produced in a higher extent than those derived
      exclusively from PEHP. These results confirm that lipid oxidation products are
      able to react with amino phospholipids analogously to protein amino groups, and
      therefore, both amino phospholipids and proteins may compete for lipid oxidation
      products. Although these results do not demonstrate the formation of pyrrolyzed
      phospholipids in vivo, they suggest that analogously to pyrrolyzed proteins,
      these modified phospholipids are likely to be produced during the phospholipid
      peroxidation process. In addition, these results also provide new bases for
      assessing the role of phospholipid modification in certain diseases,
      pathophysiological conditions, and aging.

PMID- 14680379
TI  - Interplay between MRP inhibition and metabolism of MRP inhibitors: the case of
      curcumin.
AB  - The multidrug resistance proteins MRP1 and MRP2 are efflux transporters with
      broad substrate specificity, including glutathione, glucuronide, and sulfate
      conjugates. In the present study, the interaction of the dietary polyphenol
      curcumin with MRP1 and MRP2 and the interplay between curcumin-dependent MRP
      inhibition and its glutathione-dependent metabolism were investigated using two
      transport model systems. In isolated membrane vesicles of MRP1- and MRP2
      expressing Sf9 cells, curcumin clearly inhibited both MRP1- and MRP2-mediated
      transport with IC(50) values of 15 and 5 microM, respectively. In intact
      monolayers of MRP1 overexpressing Madin-Darby canine kidney (MDCKII-MRP1) cells,
      curcumin also inhibited MRP1-mediated activity, although with a 3-fold higher
      IC(50) value than the one observed in the vesicle model. Interestingly, MRP2
      mediated activity was hardly inhibited in intact monolayers of MRP2
      overexpressing MDCKII (MDCKII-MRP2) cells upon exposure to curcumin, whereas the
      IC(50) value in the vesicle incubations was 5 microM. The difference in extent of
      inhibition of the MRPs by curcumin in isolated vesicles as compared to intact
      cells, observed especially for MRP2, was shown to be due to a swift metabolism of
      curcumin to two glutathione conjugates in the MDCKII cells. Formation of both
      glutathione conjugates was about six times higher in the MDCKII-MRP2 cells as
      compared with the MDCKII-MRP1 cells, a phenomenon that could be ascribed to the
      significantly lower glutathione levels in the cell line. The efflux of both
      conjugates, identified in the present study as monoglutathionyl curcumin
      conjugates, was demonstrated to be mediated by both MRP1 and MRP2. From dose
      response curves with Sf9 membrane vesicles, glutathionylcurcumin conjugates
      appeared to be less potent inhibitors of MRP1 and MRP2 than their parent compound
      curcumin. In conclusion, curcumin clearly inhibits both MRP1- and MRP2-mediated
      transport, but the glutathione-dependent metabolism of curcumin plays a crucial
      role in the ultimate level of inhibition of MRP-mediated transport that can be
      achieved in a cellular system. This complex interplay between MRP inhibition and
      metabolism of MRP inhibitors, the latter affecting the ultimate potential of a
      compound for cellular MRP inhibition, may exist not only for a compound like
      curcumin but also for many other MRP inhibitors presently or previously developed
      on the basis of vesicle studies.

PMID- 14680380
TI  - Computational models for predicting the binding affinities of ligands for the
      wild-type androgen receptor and a mutated variant associated with human prostate
      cancer.
AB  - In the present study, values of the binding energy (BE) were calculated for the
      rat androgen receptor on a data set of 25 steroidal and nonsteroidal compounds
      for which published values of the observed binding affinity (K(i)) are available.
      A correlation between BE and pK(i) was evident (r(2) = 0.50) for the entire data
      set and became more pronounced when the steroids and nonsteroids were plotted
      separately (r(2) congruent with 0.76). Including BE as an additional descriptor
      to supplement the default steric-electrostatic descriptors in comparative
      molecular field analysis dramatically improved the predictive ability of the
      resulting three-dimensional quantitative structure-activity relationship models.
      We also demonstrate that the observed loss in ligand specificity between the wild
      type (wt) AR and the T877A mutant AR associated with androgen-independent
      prostate cancer is reflected in decreased BE values (i.e., higher binding
      affinity) for the antiandrogen pharmaceutical hydroxyflutamide and for several
      nonandrogenic endogenous steroids, most notably cortisol, corticosterone, 17beta
      estradiol, progesterone, and 17alpha-hydroxyprogesterone.

PMID- 14680393
TI  - Is there a link between telomere maintenance and radiosensitivity?
AB  - Several recent studies point to the possibility that telomere maintenance may
      constitute a potential genetic marker of radiosensitivity. For example, the human
      diseases ataxia telangiectasia and Nijmegen breakage syndrome, which are
      characterized by clinical radiosensitivity, show alterations in telomere
      maintenance. In addition, Fanconi's anemia patients, who are characterized by
      mild cellular radiosensitivity and in some cases marked clinical
      radiosensitivity, have altered telomere maintenance. Similarly, a correlation
      between telomere maintenance and cellular radiosensitivity was reported in a
      group of breast cancer patients. Another study demonstrated that radiosensitivity
      may be more pronounced in human fibroblasts with short telomeres than in their
      counterparts with long telomeres. Several mouse models including mice deficient
      in Ku, DNA-PKcs (Prkdc), Parp and Atm, all of which are radiosensitive in vivo,
      show clear telomere alterations. The link between telomere maintenance and
      radiosensitivity is also apparent in mice genetically engineered to have
      dysfunctional telomeres. Finally, studies using non-mammalian model systems such
      as C. elegans and yeast point to the link between radiosensitivity and telomere
      maintenance. These results warrant further investigation to identify the extent
      to which these two phenotypes, namely radiosensitivity and telomere maintenance,
      are linked.

PMID- 14680394
TI  - Effects of exposure uncertainties in the TSCE model and application to the
      Colorado miners data.
AB  - The simulations in this paper show that exposure measurement error affects the
      parameter estimates of the biologically motivated two-stage clonal expansion
      (TSCE) model. For both Berkson and classical error models, we show that
      likelihood-based techniques of correction work reliably. For classical errors,
      the distribution of true exposures needs to be known or estimated in addition to
      the distribution of recorded exposures conditional on true exposures. Usually the
      exposure uncertainty biases the model parameters toward the null and
      underestimates the precision. But when several parameters are allowed to be
      dependent on exposure, e.g. initiation and promotion, then their relative
      importance is also influenced, and more complicated effects of exposure
      uncertainty can occur. The application part of this paper shows for two different
      types of Berkson errors that a recent analysis of the data for the Colorado
      plateau miners with the TSCE model is not changed substantially when correcting
      for such errors. Specifically, the conjectured promoting action of radon remains
      as the dominant radiation effect for explaining these data. The estimated
      promoting action of radon increases by a factor of up to 1.2 for the largest
      assumed exposure uncertainties.

PMID- 14680396
TI  - Survival and recovery of yeast cells after combined treatment with ionizing
      radiation and heat.
AB  - Cell survival, recovery kinetics and inactivation forms after successive and
      simultaneous treatments with gamma rays (60Co) and high temperatures were studied
      in diploid yeast cells capable of recovery. Both the extent and the rate of the
      recovery were shown to be greatly decreased with increase in the duration of heat
      treatment (60 degrees C) followed by radiation and with increase in exposure
      temperature after simultaneous treatment with heat and radiation. A quantitative
      approach describing the recovery process was used to estimate the probability of
      recovery per unit time and the irreversible component of damage after the
      combined treatment with heat and radiation. It was shown that the probability of
      recovery was independent of the conditions of the treatment with heat and
      radiation, while the irreversible component gradually increased as a function of
      the duration of heat treatment (60 degrees C) after sequential treatment with
      heat and radiation and as a function of the exposure temperature after
      simultaneous treatment with heat and radiation. The increase in the irreversible
      component was accompanied by an increase in cell death without postirradiation
      division. It is concluded on this basis that the synergistic interaction of
      ionizing radiation and hyperthermia in yeast cells is not related to the
      impairment of the recovery capacity itself and that it may be attributed to an
      increased yield of irreversible damage.

PMID- 14680395
TI  - The response of a spherical tissue-equivalent proportional counter to different
      ions having similar linear energy transfer.
AB  - The response of a tissue-equivalent proportional counter (TEPC) to different ions
      having a similar linear energy transfer (LET) has been studied. Three ions, 14N,
      20Ne and 28Si, were investigated using the HIMAC accelerator at the National
      Institute of Radiological Sciences at Chiba, Japan. The calculated linear energy
      transfer (LET( infinity )) of all ions was 44 +/- 2 keV/microm at the sensitive
      volume of the TEPC. A particle spectrometer was used to record the charge and
      position of each incident beam particle. This enabled reconstruction of the
      location of the track as it passed though the TEPC and ensured that the particle
      survived without fragmentation. The spectrum of energy deposition events in the
      TEPC could be evaluated as a function of trajectory through the TEPC. The data
      indicated that there are many events from particles that did not pass through the
      sensitive volume. The fraction of these events increased as the energy of the
      particle increased due to changes in the maximum energy of the delta rays. Even
      though the LET of the incident particles was nearly identical, the frequency
      averaged lineal energy, y(F), as well as the dose-averaged lineal energy, y(D),
      varied with the velocity of the incident particle. However, both values were
      within 15% of LET in all cases.

PMID- 14680397
TI  - Effect of antioxidant vitamins on radiation-induced apoptosis in cells of a human
      lymphoblastic cell line.
AB  - Modulating the amount of radiation-induced apoptosis by administering antioxidant
      vitamins offers a possible way to influence radiation-induced side effects in
      normal tissues. Therefore, we investigated the effect of beta-carotene, vitamin C
      and alpha-tocopherol on radiation-induced apoptosis in cells in culture. Human T
      lymphoblastic MOLT-3 cells were irradiated with a dose of 3 Gy 1 h after or
      immediately prior to the addition of vitamins in three concentrations (0.01
      microM, 1 microM and 100 microM). Eight hours later, apoptosis was scored
      morphologically by staining the nuclear DNA with Hoechst 33342. When given prior
      to irradiation, beta-carotene and vitamin E reduced the amount of radiation
      induced apoptosis significantly at concentrations of 0.01 microM and 1 microM. In
      contrast, vitamin C did not show any protective effect when given at these two
      concentrations and caused a slight but significant radiosensitization at 100
      microM. At 0.01 microM, all combinations of two vitamins showed a protective
      effect. This was also observed for the combination of all three vitamins at
      concentrations of 0.01 and 1 microM. When given immediately after irradiation,
      each of the three vitamins showed a protective effect at 0.01 microM. In
      addition, the combination of alpha-tocopherol and vitamin C reduced radiation
      induced apoptosis slightly when given at 1 microM. In all other cases, no
      statistically significant modulation of radiation-induced apoptosis was observed.
      In our experimental system, the protective effect of beta-carotene and vitamin E
      was dependent on concentration and occurred only in the micromolar and sub
      micromolar concentration range, while vitamin C alone, but not in combinations,
      had a sensitizing effect, thus arguing for a careful consideration of vitamin
      concentrations in clinical settings.

PMID- 14680398
TI  - Comparison of endogenous TP53 genomic status with clonogenicity and different
      modes of cell death after X irradiation.
AB  - Although extensive data indicate that the tumor suppressor TP53 modifies the
      radiation responses of human and rodent cells, the exact relationship between
      TP53 and radiation responsiveness remains controversial. To elucidate the
      relevance of endogenous TP53 genomic status to radiosensitivity in a cell-type
      independent manner, different cells of 10 human tumor cell lines with different
      tissues of origin were examined for TP53 status. The TP53 status was compared
      with radiation-related cell survival parameters (D(q), D(0), SF2) and with the
      mode of cell death. Different modes of cell death were examined by measuring
      radiation-induced micronucleation, apoptosis and abnormal cells. Alterations of
      the TP53 gene were detected in eight cell lines. No splicing mutation was found.
      Five cell lines showed codon 68 polymorphism. Codon 72 alterations were found in
      four cell lines. "Hot spot" alterations were detected in only two of 10 cell
      lines. Although the cells differed widely in survival parameters (D(q), D(0),
      SF2) and modes of cell death (micronucleation/apoptosis/abnormal cells) after
      irradiation, significant cell-type-independent correlations were obtained between
      the multiple cell death parameter micronucleation/apoptosis/abnormal cells and
      SF2 (P < 0.001) and D(q) (P = 0.003). Moreover, cells with a wild-type TP53 gene
      were more resistant to X rays than cells with a mutated TP53 gene or cells that
      were TP53-deficient. The alterations within exons 5-10 of the TP53 correlated
      with a enhanced radiosensitivity. For the first time, we demonstrated a
      correlation between endogenous genetic alterations within exons 5-10 of TP53 and
      radiation-related cell survival and cell death. This indicates a new molecular
      relevance of TP53 status to intrinsic cellular radiosensitivity.

PMID- 14680399
TI  - Identification of differentially expressed genes in mouse kidney after
      irradiation using microarray analysis.
AB  - Irradiation of the kidney induces dose-dependent, progressive renal functional
      impairment, which is partly mediated by vascular damage. The molecular mechanisms
      underlying the development of radiation-induced nephropathy are unclear. Given
      the complexity of radiation-induced responses, microarrays may offer new
      opportunities to identify a wider range of genes involved in the development of
      radiation injury. The aim of the present study was to determine whether
      microarrays are a useful tool for identifying time-related changes in gene
      expression and potential mechanisms of radiation-induced nephropathy. Microarray
      experiments were performed using amplified RNA from irradiated mouse kidneys (1 x
      16 Gy) and from sham-irradiated control tissue at different intervals (1-30
      weeks) after irradiation. After normalization procedures (using information from
      straight-color, color-reverse and self-self experiments), the differentially
      expressed genes were identified. Control and repeat experiments were done to
      confirm that the observations were not artifacts of the array procedure (RNA
      amplification, probe synthesis, hybridizations and data analysis). To provide
      independent confirmation of microarray data, semi-quantitative PCR was performed
      on a selection of genes. At 1 week after irradiation (before the onset of
      vascular and functional damage), 16 genes were significantly up-regulated and 9
      genes were down-regulated. During the period of developing nephropathy (10 to 20
      weeks), 31 and 42 genes were up-regulated and 9 and 4 genes were down-regulated.
      At the later time of 30 weeks, the vast majority of differentially expressed
      genes (191 out of 203) were down-regulated. Potential genes of interest included
      TSA-1 (also known as Ly6e) and Jagged 1 (Jag1). Increased expression of TSA-1, a
      member of the Ly-6 family, has previously been reported in response to
      proteinuria. Jagged 1, a ligand for the Notch receptor, is known to play a role
      in angiogenesis, and is particularly interesting in the context of radiation
      induced vascular injury. The present study demonstrates the potential of
      microarrays to identify changing patterns of gene expression in irradiated
      kidney. Further studies will be required to evaluate functional involvement of
      these genes in vascular-mediated normal tissue injury.

PMID- 14680400
TI  - Radiation response of neural precursor cells: linking cellular sensitivity to
      cell cycle checkpoints, apoptosis and oxidative stress.
AB  - Therapeutic irradiation of the brain can cause a progressive cognitive
      dysfunction that may involve defects in neurogenesis. In an effort to understand
      the mechanisms underlying radiation-induced stem cell dysfunction, neural
      precursor cells isolated from the adult rat hippocampus were analyzed for acute
      (0-24 h) and chronic (3-33 days) changes in apoptosis and reactive oxygen species
      (ROS) after exposure to X rays. Irradiated neural precursor cells exhibited an
      acute dose-dependent apoptosis accompanied by an increase in ROS that persisted
      over a 3-4-week period. The radiation effects included the activation of cell
      cycle checkpoints that were associated with increased Trp53 phosphorylation and
      Trp53 and p21 (Cdkn1a) protein levels. In vivo, neural precursor cells within the
      hippocampal dentate subgranular zone exhibited significant sensitivity to
      radiation. Proliferating precursor cells and their progeny (i.e. immature
      neurons) exhibited dose-dependent reductions in cell number. These reductions
      were less severe in Trp53-null mice, possibly due to the disruption of apoptosis.
      These data suggest that the apoptotic and ROS responses may be tied to Trp53
      dependent regulation of cell cycle control and stress-activated pathways. The
      temporal coincidence between in vitro and in vivo measurements of apoptosis
      suggests that oxidative stress may provide a mechanistic explanation for
      radiation-induced inhibition of neurogenesis in the development of cognitive
      impairment.

PMID- 14680401
TI  - Adaptive response in embryogenesis: IV. Protective and detrimental bystander
      effects induced by X radiation in cultured limb bud cells of fetal mice.
AB  - The radioadaptive response and the bystander effect represent important phenomena
      in radiobiology that have an impact on novel biological response mechanisms and
      risk estimates. Micromass cultures of limb bud cells provide an in vitro cellular
      maturation system in which the progression of cell proliferation and
      differentiation parallels that in vivo. This paper presents for the first time
      evidence for the correlation and interaction in a micromass culture system
      between the radioadaptive response and the bystander effect. A radioadaptive
      response was induced in limb bud cells of embryonic day 11 ICR mice. Conditioning
      irradiation of the embryonic day 11 cells with 0.3 Gy resulted in a significant
      protective effect against the occurrence of apoptosis, inhibition of cell
      proliferation, and differentiation induced by a challenging dose of 5 Gy given
      the next day. Both protective and detrimental bystander effects were observed;
      namely, irradiating 50% of the embryonic day 11 cells with 0.3 Gy led to a
      successful induction of the protective effect, and irradiating 70% of the
      embryonic day 12 cells with 5 Gy produced a detrimental effect comparable to that
      seen when all the cells were irradiated. Further, the bystander effect was
      markedly decreased by pretreatment of the cells with an inhibitor to block the
      gap junction-mediated intercellular communication. These results indicate that
      the bystander effect plays an important role in both the induction of a
      protective effect by the conditioning dose and the detrimental effect of the
      challenge irradiation. Gap junction-mediated intercellular communication was
      suggested to be involved in the induction of the bystander effect.

PMID- 14680402
TI  - Chromatin organization contributes to non-randomly distributed double-strand
      breaks after exposure to high-LET radiation.
AB  - The influence of higher-order chromatin structure on the non-random distribution
      of DNA double-strand breaks induced by high-LET radiation was investigated. Five
      different chromatin structures (intact cells, condensed and decondensed
      chromatin, nucleoids and naked genomic DNA) from GM5758 cells or K562 cells were
      irradiated with (137)Cs gamma-ray photons and 125 keV/microm nitrogen ions (16-25
      MeV/nucleon). DNA was purified with a modified lysis procedure to avoid release
      of heat-labile sites, and fragment size distributions and double-strand break
      yields were analyzed by different pulsed-field gel electrophoresis protocols.
      Whereas double-strand breaks in photon-irradiated cells were randomly
      distributed, irradiation of intact K562 cells with high-LET nitrogen ions
      produced an excess of non-randomly distributed DNA fragments 10 kb-1 Mbp in size.
      Complete removal of proteins eliminated this non-random component. There was a
      gradual increase in the yield of double-strand breaks for each chromatin
      decondensation step, and compared to intact cells, the yields for naked DNA (in
      buffer without scavengers) increased 83 and 25 times after photon and nitrogen
      ion irradiation, respectively. The corresponding relative biological
      effectiveness decreased from 1.6-1.8 for intact cells to 0.49 for the naked DNA.
      We conclude that the organization of DNA into chromatin fiber and higher-order
      structures is responsible for the majority of non-randomly distributed double
      strand breaks induced by high-LET radiation. However, our data suggest a complex
      interaction between track structure and chromatin organization over several
      levels.

PMID- 14680412
TI  - Overview of partial compliance.
AB  - A substantial proportion of patients with psychiatric and nonpsychiatric chronic
      illnesses fail to take their medications as prescribed. A number of studies
      suggest that 50% or more of individuals with schizophrenia are noncompliant with
      medications at some time during their illness. In most cases, patients are
      partially compliant, taking only a portion of their prescribed medications.
      Noncompliance is probably the most important element contributing to relapse in
      schizophrenia. Factors contributing to the rate of noncompliance include
      medication side effects, the severity of psychotic symptoms, impaired cognition,
      and an inadequate understanding of the role of medication for preventing relapse.
      In addition, both patients and clinicians overestimate patients' compliance.
      Strategies for managing partial compliance include the treatment of medication
      side effects, the education of patients about their illness, and the use of long
      acting antipsychotic formulations.

PMID- 14680413
TI  - Factors influencing compliance in schizophrenia patients.
AB  - Scientifically, compliance can be expressed as the ratio between an observed
      treatment behavior and given treatment standards. Although the factors that
      influence compliance often overlap or influence each other, it is possible to
      differentiate between factors that are related to the patient, the patient's
      environment, the treating clinician, and treatment itself. Although this
      differentiation is in some ways artificial, it may aid the practicing clinician
      in assessing the various reasons why a particular patient is likely to develop or
      has already developed compliance problems. The fact that a number of
      circumstances and parties are involved in the multifaceted issue of compliance
      makes it evident that patients must never be solely blamed for compliance
      problems. Despite the fact that compliance behavior is difficult to study from a
      methodological point of view, the scientific information available to date does
      provide many important leads for the engaged clinician to prevent and manage
      compliance problems.

PMID- 14680414
TI  - Relapse and rehospitalization: comparing oral and depot antipsychotics.
AB  - A review of studies that compared conventional oral and depot antipsychotic
      medications highlighted the following points. Mirror-image studies in which
      patients served as their own controls provided evidence of substantial benefit
      for depot injectable medications. The randomized clinical trials did not, in
      general, support the findings of significant decrease in relapse rates between
      these 2 routes of administration. Across the studies reviewed, the 1-year relapse
      rate for long-acting depot medication was 27% compared with 42% for patients who
      received oral medication. The 27% risk of relapse in patients who received
      guaranteed depot medication suggests that relapse is not always driven by
      noncompliance. In the only study that lasted for 2 years, the risk of relapse
      decreased substantially in the depot-treated patients, suggesting that risk of
      noncompliance may be a more important factor in relapse over extended periods of
      time. A recent formal meta-analytic review of depot medications concluded that
      this route of administration resulted in clinical advantages in terms of global
      outcome.

PMID- 14680415
TI  - Comparison of the effects of different routes of antipsychotic administration on
      pharmacokinetics and pharmacodynamics.
AB  - Clinicians face a dilemma when choosing between short-acting atypical
      antipsychotics and long-acting conventional antipsychotics. Atypical
      antipsychotics offer better safety and efficacy, while depot formulations of
      conventional antipsychotics provide more reliable drug delivery, reduced
      differences in peak and trough plasma levels of drug, and greater dosing
      precision. Risperidone was recently approved by the U.S. Food and Drug
      Administration as the first atypical long-acting antipsychotic medication, given
      as biweekly gluteal injections. This long-acting formulation is synthesized using
      a microsphere encapsulation process, and gradual hydrolysis of the copolymer
      encapsulating the drug provides a steady release of medication. Consistent with
      other long-acting medications, plasma drug level fluctuation is reduced more with
      long-acting than with oral risperidone. Analyses are currently underway to
      further examine safety outcomes with long-acting risperidone.

PMID- 14680416
TI  - Choice of maintenance medication for schizophrenia.
AB  - Unmedicated schizophrenia patients relapse at a rate of approximately 10% per
      month. Maintenance treatment with antipsychotic medications can reduce this rate
      dramatically. Ensuring compliance with medication in the maintenance treatment of
      schizophrenia encompasses 3 areas of concern: (1) choice of antipsychotic
      medication, accounting for efficacy and side effects; (2) route of administration
      of medications, considering the benefits and detriments of long-acting injectable
      and oral medications; and (3) reducing "doctor noncompliance," the failure of
      some physicians to perceive the need for long-term treatment for patients with
      chronic schizophrenia. This article focuses on the selection of the antipsychotic
      medication that will most likely lead to successful maintenance treatment of
      schizophrenia. Data from acute trials must be relied upon to evaluate the
      comparative risks and benefits of these agents as long-term treatments since few
      double-blind, random-assignment studies have compared the newer-generation
      antipsychotics for maintenance treatment of schizophrenia. Studies of acute
      treatment, as well as a small number of studies of maintenance treatment, have
      shown the newer-generation antipsychotics risperidone and olanzapine to be more
      efficacious and to have a more favorable side effect profile than conventional
      generation antipsychotics. Research on the newer-generation antipsychotics,
      including ziprasidone, aripiprazole, and quetiapine, shows these agents to be
      efficacious and safe, although the limited amount of data on these agents
      precludes a definitive evaluation of their efficacy and safety.

PMID- 14680417
TI  - Strategies for improving compliance in treatment of schizophrenia by using a long
      acting formulation of an antipsychotic: clinical studies.
AB  - Despite evidence showing the importance of continuous medication in preventing
      relapse in patients with schizophrenia and the harmful consequences that relapse
      can have, clinical efforts often focus on hospital-based treatment or treatment
      of acute exacerbations of schizophrenia rather than on ensuring appropriate and
      effective relapse prevention. Inadequate compliance with antipsychotic treatment
      further deters from the goal of long-term management of schizophrenia; however,
      appropriate use of injectable, long-acting antipsychotic medications--especially
      atypical antipsychotics--has the potential to increase compliance and thus
      improve the long-term prognosis of patients with schizophrenia. A long-acting
      formulation of the atypical antipsychotic risperidone has undergone large-scale
      clinical testing, during which it showed significant improvement on measures of
      disease severity while maintaining an acceptable side effect profile.

PMID- 14680418
TI  - Clinical guidelines: Dosing and switching strategies for long-acting risperidone.

PMID- 14680419
TI  - Efficacy and effectiveness of first- and second-generation antipsychotics in
      schizophrenia.
AB  - While efficacy as a concept is concerned with whether a treatment works under
      ideal conditions, effectiveness is concerned with whether a treatment works under
      the conditions of routine care. Large-scale clinical, pharmacy, and
      administrative databases can provide naturalistic data for effectiveness studies
      when appropriate methodology is employed. The Nathan Kline Institute Integrated
      Research Database includes patient-specific admission, demographic, diagnostic,
      medication, and discharge information from hospitals operated by the New York
      State Office of Mental Health. This database was used to study the effectiveness
      of first- versus second-generation antipsychotics in the treatment of
      schizophrenia and schizoaffective disorder. Switching off the index medication
      regimen prior to discharge (negative outcome) was our principal outcome of
      interest. We concluded that, as a class, second-generation antipsychotics were
      less likely than first-generation agents to be associated with premature
      discontinuation of an antipsychotic regimen, both when used as the initial
      medication regimen following hospitalization and as the second regimen following
      a prior medication switch.

PMID- 14680420
TI  - Similarities and differences among antipsychotics.
AB  - Most antipsychotic drugs act equivalently and potently on the symptoms of
      schizophrenia, with clozapine as the notable exception. Negative symptoms and
      cognitive deficits are strongly associated with poor prognosis; some reports
      suggest that these symptoms respond better to second- than to first-generation
      antipsychotics. Although second-generation antipsychotics exert their action
      through a blockade of dopamine and serotonin receptors (and some have a more
      complex action), each has a different set of pharmacologic characteristics,
      including side effects. Due to the differences among antipsychotics available
      today, optimizing treatment for individual patients requires choosing the most
      appropriate drug and, if necessary, switching to a different drug if the first
      proves unsatisfactory. The treating physician must carefully match the diverse
      needs of schizophrenic patients with the varied characteristics of the second
      generation antipsychotics.

PMID- 14680422
TI  - The economic and human impact of new drugs.
AB  - The benefits of new drugs to society exceed their cost by a substantial margin.
      These benefits include net decrease in overall medical expenditures, reduced
      limitations on work and other activities contributing to quality of life, and
      increased longevity. Further, new drugs contribute to health and economic growth
      in the United States. Formularies, to the extent that they restrict drug choices,
      restrict access to new drugs.

PMID- 14680421
TI  - Impact of formularies on clinical innovation.
AB  - It is important to consider, in light of how innovation has so often occurred,
      whether today's managed care environment is conducive to continued
      psychopharmacologic innovation. The initial step in the development of a new area
      in psychopharmacology has historically relied in large part on individual
      clinicians who pursued unconventional methods of treatment. When a set of
      guidelines such as a formulary (a list of drugs eligible for reimbursement
      compiled by a managed care organization) becomes restrictive, it decreases
      clinician innovation. In addition to this long-term threat to innovation, studies
      have found greater restrictiveness in formularies to be associated with higher
      health care utilization. Thus, restricted formularies that are based on a naive
      interpretation of "therapeutic equivalence" may slow the advance of medical
      science without even achieving the only goal that could possibly justify such
      restrictions-cost control. If innovation is to flourish, formularies must be
      flexible and advisory, not restrictive. Preserving the climate for innovation in
      health care requires the management culture to focus on the long-term impact of
      policies on quality and innovation as well as on the overall health cost in the
      system.

PMID- 14680423
TI  - Unintended outcomes of medicaid drug cost-containment policies on the chronically
      mentally ill.
AB  - Cost-containment policies frequently focus on reducing drug expenditures,
      although prescription drug costs are a relatively small proportion of total
      health care expenditures. Data show that very few drug cost-containment policies
      can selectively reduce unneeded care while maintaining essential care. In the
      early 1980s, the New Hampshire Medicaid program introduced a drug-payment limit
      (a "cap") that set the number of reimbursable medications a patient could receive
      per month at 3. Analyses reviewed in this article indicate that New Hampshire's
      drug cap, while in effect, reduced the use of prescription drugs among the
      elderly and the mentally ill but increased hospital and nursing home admissions,
      partial hospitalizations, distribution of psychoactive medications by community
      mental health centers, and use of emergency mental health services. Vulnerable
      populations are most likely to experience adverse effects from hastily-applied
      drug cost-containment policies, and resulting compensatory measures may create
      more expenses than the policy removes.

PMID- 14680424
TI  - Limiting access to psychiatric services can increase total health care costs.
AB  - Restricted access to health care services and medication is associated with
      overall higher utilization and higher health care costs. Although randomized
      controlled trials (RCTs) are regarded as the best method of determining whether a
      treatment strategy does more good than harm, clinical practice improvement (CPI)
      methods may be a more effective way of achieving superior medical outcomes for
      the least cost over the course of a patient's care. The Managed Care Outcomes
      Project, a large-scale CPI study, tracked detailed factors regarding medical
      care, patients, and outcomes from different managed care settings. Results showed
      that cost-containment strategies employed by various health maintenance
      organizations were associated with poor treatment outcomes for patients and in
      fact increased total health care costs. Psychiatric illnesses were
      underdiagnosed, and care ranged from patients receiving psychiatric medications
      without a psychiatric diagnosis to patients with a psychiatric diagnosis
      receiving no psychiatric treatment at all. Cost-containment strategies appeared
      to limit psychiatric referrals, frequency of psychiatric visits, and use of
      certain antidepressants (i.e., selective serotonin reuptake inhibitors). Further,
      the severity of the primary physical illness in the study population was
      associated with greater psychiatric illness. The fact that treatment was
      inconsistent and frequently inappropriate shows the need for better diagnostic
      and management protocols.

PMID- 14680426
TI  - Commentary: purchasing community perspective.

PMID- 14680425
TI  - Weighing the evidence: trends in managed care formulary decision making.
AB  - Health plans, pharmacy benefit managers, and other organizations use drug
      formularies to promote quality care while controlling costs. However, restrictive
      formularies are often viewed as constraints on physician practice and potential
      barriers to optimal patient care. Reluctance to add new drugs to an established
      formulary is rational economic behavior. Innovative compounds may have unknown
      properties with uncertain outcomes and therefore may impose costs in the form of
      risk. Products that seemingly duplicate drugs already on formulary may increase
      transaction costs without additional benefit. In evaluating new products,
      formulary managers face the task of identifying, assembling, and synthesizing a
      wide range of complex information. Manufacturers, who may be in the best position
      to supply that information, have been severely restricted by U.S. Food and Drug
      Administration (FDA) regulations that limited marketing communications to
      findings from well-controlled clinical trials. The FDA Modernization Act of 1997
      eased these restrictions somewhat by acknowledging that sophisticated purchasers
      such as organized health plans were capable of weighing the quality and
      impartiality of manufacturer-supplied evidence. The Academy of Managed Care
      Pharmacy (AMCP) created a standardized template that formularies can use to
      request comprehensive information about specific drugs from manufacturers.
      Widespread adoption of the AMCP format by health plans and manufacturers will
      greatly increase access to information about new drugs, speeding the process of
      formulary committee deliberation, and instilling greater confidence in the
      outcome of those decisions. Wider access to new drugs may result.

PMID- 14680427
TI  - Commentary: health care organization perspective.

PMID- 14680428
TI  - Commentary: government perspective.

PMID- 14680429
TI  - Commentary: advocacy perspective.

PMID- 14680430
TI  - Insulin glargine: commentary on the duration of action and lower risk of
      nocturnal hypoglycaemia in patients with diabetes.

PMID- 14680431
TI  - Medical treatment of rosacea with emphasis on topical therapies.
AB  - Due to the development and release of newer topical formulations, the diagnosis
      and treatment of rosacea has received renewed attention over the past 3-5 years
      both in the literature and at medical symposia. Rosacea is a very common facial
      dermatosis. In the US, rosacea is estimated to affect > 14 million people,
      predominantly adults with approximately 60% of cases diagnosed before the age of
      50. A frustrating aspect of the disease is its inherent chronicity punctuated
      with periods of exacerbation and relative remission. A variety of subtypes have
      been identified which correlate with clinical presentation. Although the
      pathogenesis of rosacea is poorly understood, multiple topical agents are
      available. The efficacy of topical therapy for rosacea relates primarily to
      reduction in inflammatory lesions (papules, pustules), decreased intensity of
      erythema, a reduction in the number and intensity of flares and amelioration of
      symptoms, which may include stinging, pruritus and burning. The list of main
      topical agents utilised for the treatment of rosacea include metronidazole,
      sulfacetamide-sulfur, azelaic acid and topical antibiotics (clindamycin,
      erythromycin). Depending on the severity at initial presentation, topical therapy
      may be combined with systemic antibiotic therapy (e.g., oral tetracycline
      derivative). Newer therapeutic choices primarily involve improved vehicle
      formulations, which demonstrate favourable skin tolerability and cosmetic
      elegance.

PMID- 14680432
TI  - Pharmacodynamics of antibiotics in the respiratory tree.
AB  - For an antibiotic to be active in vivo, the concept of high tissue concentrations
      at infected sites has been popular for a long time, but has recently been
      criticised. The measurement of antibiotic tissue levels in humans is restricted
      by ethical issues, the cost of investigations and doubtful clinical significance.
      In the respiratory tree (RT), antibiotic concentrations have been studied. It has
      been shown that the antibiotic concentrations in both the lung tissue and fluids
      are related to three factors: the frequency of community and severe hospital
      respiratory infections; the wide prescription of antibiotics in cases of
      respiratory infections; and the easy access of sampling different areas of the
      RT. Due to the controversial perception of these studies, new pharmacological
      approaches have been developed using animal models, in vitro simulation of
      antibiotic kinetics in human serum and the involvement of pathogens, thus
      resulting in new pharmacodynamic parameters. This review looks at the concepts in
      antibiotic concentrations and the pharmacodynamics of the RT.

PMID- 14680433
TI  - Recent progress in the pharmacotherapy of Churg-Strauss syndrome.
AB  - Churg-Strauss syndrome (CSS) is a primary systemic vasculitis occurring primarily
      in patients with asthma. Unlike other small vessel vasculitides, CSS is
      characterised by blood and tissue eosinophilia. Corticosteroids are the therapy
      of first choice for all stages of the disease when active vasculitis needs to be
      treated rapidly. In patients with severe disease and organ- or life-threatening
      manifestation, the addition of cyclophosphamide appears to improve the outcome
      and reduces the incidence of relapses. In cases with an apparently better
      prognosis and less severe disease, methotrexate can be given as a corticosteroid
      sparing agent in order to reduce the cumulative dose of corticosteroids, which is
      generally high in most cases as long-term administration of corticosteroids is
      often inevitable in order to control asthma, even if the vasculitis is inactive.
      In very severe cases of CSS, cyclophosphamide and corticosteroids may be
      insufficient to induce remission. In these cases, anti-TNF blocking agents such
      as infliximab or etanercept, may be added for a limited period of time. As this
      intense immunosuppression increases the risk for infections, a prophylaxis with
      sulfamethoxazole/trimethoprim is advised. Alternatively, the administration of
      recombinant IFN-alpha can be a effective when given on a short-term basis in
      otherwise refractory cases. Whether a continuous administration of
      immunosuppressive agents in addition to corticosteroids can reduce the frequency
      of relapses in CSS who are in remission is still unknown. As relapses occur in >
      25% of all patients, studies addressing the prevention of relapses in CSS are
      highly desirable in the future.

PMID- 14680434
TI  - Current therapy of ulcerative colitis in children.
AB  - Ulcerative colitis presents in childhood in 10% of those affected, usually with
      pancolitis. Important features in management include growth, development and
      avoidance of treatment toxicity. This review addresses the current treatment
      options including both the paediatric evidence-based experience and areas where
      paediatric practice is informed by adult studies. Standard treatments include
      sulfasalazine or 5-aminosalicylates, corticosteroids, purine derivatives
      (azathioprine or 6-mercaptopurine) and surgery. Other immunosuppressant therapies
      and the emerging roles for biological therapies and probiotics are discussed.

PMID- 14680435
TI  - Acute diverticulitis of the colon--current medical therapeutic management.
AB  - Diverticular disease of the colon is very common in developed countries with its
      prevalence increasing with age, varying from < 10% in those < 40 years of age, to
      an estimated 50-66% of patients > 80 years of age. Diverticulitis, defined as
      inflammation and/or infection associated with diverticula, is the most common
      clinical complication of this disorder, affecting an estimated 10-25% of patients
      with colonic diverticula. The therapeutic measures aim at putting the intestine
      'at rest', thus resolving the infection, the consequences of the inflammation and
      preventing or limiting complications. For patients with severe and complicated
      diverticulitis, ampicillin, gentamicin, metronidazole, piperacillin and
      tazobactam are the antibiotics successfully used in clinical practice, whereas
      ciprofloxacin, metronidazole and more recently, rifaximin, have been successfully
      used in the treatment of uncomplicated diverticular disease. Mesalazine (alone or
      in association with antibiotics) and probiotics are the two latest therapies for
      the treatment of diverticulitis which have been developed in the last few years.
      In fact, the combination of mesalazine and an antibiotic showed significant
      superiority in improving the severity of symptoms, bowel habits and in preventing
      symptomatic recurrence of diverticulitis than antibiotics alone, but probiotics
      also seem to be effective in preventing recurrence of the disease. In light of
      the excellent results obtained in the treatment of inflammatory bowel disease and
      irritable bowel syndrome, it is probable that probiotics may be the future best
      treatment also for mild-to-moderate uncomplicated attacks of acute
      diverticulitis, especially if used with salycilates.

PMID- 14680436
TI  - Management of reactive arthritis.
AB  - Reactive arthritis (ReA) is an aseptic form of articular inflammation induced by
      infections mainly localised in the gastrointestinal (enteroarthritis) or
      urogenital (uroarthritis) tracts. The bacteria principally involved as causative
      agents are Chlamydia, Salmonella, Shigella, Campylobacter and Yersinia. The
      clinical picture is usually characterised by a mono-oligoarthritis of the lower
      limbs. Axial involvement is possible and extra-articular manifestations such as
      enthesitis, tenosynovitis, bursitis and dactylitis are frequent. NSAIDs and
      sulfasalazine are still the drugs most commonly used in the treatment of ReA.
      Steroids are administered when inflammatory symptoms are resistant to NSAIDs.
      Experiences with other DMARDs (disease modifying antirheumatic drugs) such as
      azathioprine, methotrexate and cyclosporin, have been sporadically reported and
      they can be employed in patients that are unresponsive to the more usual
      medicaments. The intake of antibacterials (tetracyclines) may be useful in
      uroarthritis but have not been so successful in enteroarthrits. In more
      aggressive cases, or when ReA evolves towards ankylosing spondylitis, TNF-alpha
      blockers could represent an effective choice.

PMID- 14680437
TI  - A comparison of current neuroblastoma chemotherapeutics.
AB  - Neuroblastoma is the most common solid tumour in childhood. Modern management
      includes a biopsy to perform genetic studies. Based on clinical data and Myc-N
      amplification (MNA), patients are divided in three prognostic groups: the low
      risk (Stage 1, 2, 4S without MNA) has an event-free survival (EFS) of > 90% with
      surgery alone; the intermediate-risk (Stage 3, > 1 year of age, without MNA and
      Stage 3 and 4 infants without MNA) has an EFS of approximately 80% with mild
      chemotherapy and surgery; the high-risk group includes Stage 4, > 1 year of age
      and any stage and age with MNA. These patients are treated with chemotherapy,
      surgery, megatherapy, irradiation and 13-cis-retinoic acid. With this complex
      therapy, a 5-year EFS of 30-50% can be obtained.

PMID- 14680438
TI  - Trastuzumab-based combination therapy for breast cancer.
AB  - Trastuzumab, a humanised monoclonal antibody directed against the extracellular
      domain of HER-2, has been shown to be active against HER-2-overexpressing
      metastatic breast cancer, either as single agent or when used in combination with
      chemotherapy. In preclinical models, trastuzumab has shown additive and even
      synergistic anti-tumour activity with the most active chemotherapeutic agents
      used in the treatment of breast cancer. In a large, randomised, Phase III trial,
      the combination of trastuzumab plus chemotherapy was shown to improve response
      rate and survival. The high incidence of cardiotoxicity seen with the combination
      of trastuzumab plus anthracycline drugs prompted carrying out of several clinical
      studies combining trastuzumab with other chemotherapeutic agents, including
      docetaxel, vinorelbine, platinum salts, gemcitabine and capecitabine. This
      article summarises the available data on trastuzumab-based combinations for
      breast cancer.

PMID- 14680439
TI  - Haematopoietic stem cell transplantation: indications, clinical developments and
      future directions.
AB  - Haematopoietic stem cell transplantation (HSCT) is an established curative
      treatment for many malignant and non-malignant diseases. Over the last two
      decades, novel approaches have resulted in significant reductions in the
      morbidity and mortality associated with HSCT. These include the utilisation of
      reduced intensity regimens, more effective graft versus host disease prophylaxis,
      exploration of new sources of progenitor haematopoietic stem cells and better
      prophylaxis and treatment of infections. Despite current advances, new strategies
      are needed to further reduce the complications associated with HSCT. This article
      reviews the current indications for HSCT and the recent progress in the field of
      both allogeneic- and autologous HSCT.

PMID- 14680440
TI  - The role of aspirin in cardiovascular diseases--forgotten benefits?
AB  - The increasing burden of cardiovascular diseases in developed, as well as
      developing countries, underscores the need for the more widespread and
      appropriate use of aspirin in secondary prevention of occlusive vascular events
      during acute evolving myocardial infarction (MI) and in primary prevention.
      Aspirin should be far more widely used in a wide range of patients who have
      suffered a prior occlusive vascular event and in all patients suffering acute MI
      or occlusive stroke. Finally, in primary prevention, aspirin should be considered
      for individuals whose 10-year risks of a coronary event are > or = 10%, as an
      adjunct not alternative to the management of other risk factors. The more
      widespread and appropriate use of aspirin will avoid many premature deaths in
      secondary prevention and MIs in primary prevention.

PMID- 14680442
TI  - Review of cetirizine hydrochloride for the treatment of allergic disorders.
AB  - Cetirizine hydrochloride is an orally-active and selective histamine (H(1))
      receptor antagonist. It is a second-generation antihistamine and a human
      metabolite of hydroxyzine. Therefore, its principal effects are mediated via
      selective inhibition of peripheral H(1) receptors. The antihistaminic activity of
      cetirizine has been documented in a variety of animal and human models. In vivo
      and ex vivo animal models have shown negligible anticholinergic and
      antiserotonergic activity. In clinical studies, however, dry mouth has been seen
      more commonly with cetirizine than with placebo. In vitro receptor binding
      studies have shown no measurable affinity for receptors other than H(1)
      receptors. Auto-radiographical studies with radiolabelled cetirizine in the rat
      have shown negligible penetration into the brain. Ex vivo experiments in the
      mouse have shown that systemically administered cetirizine does not significantly
      occupy cerebral H(1) receptors. Impairment of CNS function is comparable to other
      low-sedating antihistamines at the recommended dose of 10 mg/day for adults. It
      has anti-inflammatory properties that may play a role in asthma management. It
      does not interact with concomitantly administered medications, it has no cardiac
      adverse effects, and it does not appear to be associated with teratogenicity.
      Cetirizine is predominantly eliminated by the kidneys with a mean elimination
      half-life is 8.3 h. It is rapidly absorbed, and significant clinical inhibition
      of a wheal and flare response occurs in infants, children and adults within 20
      min of a single oral dose and persists for 24 h. No tolerance to the wheal and
      flare response occurs even after 1 month of daily treatment. The clinical
      efficacy of cetirizine for allergic respiratory diseases has been established in
      numerous trials. There is evidence that cetirizine improves symptoms of
      urticaria. Concomitant use of cetirizine also decreases the duration and amount
      of topical anti-inflammatory preparations needed for the treatment of atopic
      dermatitis. Interestingly, several clinical studies suggest that cetirizine may
      be useful in the treatment and prevention of mild asthma.

PMID- 14680441
TI  - Aggrenox((R)) versus other pharmacotherapy in preventing recurrent stroke.
AB  - Stroke is the third leading cause of death in the US with recurrent events a high
      likelihood in those who survive an initial event. The long-term goal of therapy
      is to prevent the recurrence of stroke and other atherosclerotic events. Aspirin
      has been the first-line agent for stroke prevention for a long time. As new
      antiplatelet agents have been introduced, their role in the secondary prevention
      of stroke remains to be defined. In particular, the role of the combination of
      aspirin and modified-release dipyridamole (Aggrenox, Boehringer Ingelheim Corp.),
      the newest product, in the secondary prevention of stroke, remains unknown. The
      purpose of this manuscript is to review the evidence of these antiplatelet agents
      in the secondary prevention of stroke and arrive at a conclusion specifically
      regarding the role of Aggrenox. Clinical studies which examined stroke as a
      single primary outcome or as one event in a combined primary outcome will be
      reviewed.

PMID- 14680443
TI  - Review of rabeprazole in the treatment of gastro-oesophageal reflux disease.
AB  - Gastro-oesophageal reflux disease (GERD) is an increasing health problem in
      developed countries and is associated with enormous costs in terms of reduced
      quality of life, loss of productivity, health expenses and mortality. The
      gastrointestinal disease with the highest annual direct costs in the US (in the
      year 2000) was GERD (9.3 billion US dollars). GERD is primarily a motility
      disorder of the oesophagus, however, there are no available promotility drugs on
      the market. The main symptoms are heartburn and acid regurgitation arising from
      the reflux of gastric acid, which is the only factor at present suited for
      pharmacological intervention. The proton pump inhibitors (PPIs) give optimal
      benefit in the treatment of GERD. The sales of PPIs in the year 2002 amounted to
      12 billion US dollars in North America and 4 billion US dollars in Europe and the
      sales have been increasing by > 10% annually. This paper reviews the use of PPIs
      in the treatment of GERD with particular focus on one of the newer agents,
      rabeprazole.

PMID- 14680444
TI  - Efficacy and safety of tamsulosin in the treatment of urological diseases.
AB  - The alpha(1)-adrenoceptor antagonist, tamsulosin, is selective for alpha(1A)- and
      alpha(1D)- over alpha(1B)-adrenoceptors. Both placebo-controlled and comparative
      studies with other agents have demonstrated tamsulosin to be an effective
      treatment for patients with lower urinary symptoms suggestive of benign prostatic
      hyperplasia. Its effectiveness appears to be maintained over many years.
      Tamsulosin may also effectively reduce lower urinary tract symptoms in other
      urological diseases. A dose of tamsulosin 0.4 mg/day has a tolerability close to
      that of placebo and has little, if any, blood pressure lowering effects.
      Tolerability and lack of blood pressure lowering are maintained even in high-risk
      patients such as those with cardiovascular comorbidity and/or comedication. Apart
      from adrenoceptor subtype-selectivity, a smooth pharmacokinetic profile of its
      modified-release formulation and a selective accumulation in target tissues may
      contribute to an excellent efficacy:tolerability ratio.

PMID- 14680445
TI  - Donepezil: a clinical review of current and emerging indications.
AB  - This article reviews the piperidine derivative, donepezil hydrochloride (E2020,
      Aricept), a reversible central acetylcholinesterase inhibitor currently approved
      for treatment of mild-to-moderate Alzheimer's disease. Donepezil is well absorbed
      orally, unaffected by food or by time of administration; it reaches therapeutic
      levels in doses of 5-10 mg/day and peak plasma concentrations are obtained 3-4 h
      after oral administration. A single bedtime dose is recommended due to the long
      elimination half-life of the drug (70 h). Donepezil does not cause liver toxicity
      or significant drug interactions and is relatively well-tolerated. Initial side
      effects include nausea, vomiting, diarrhoea, insomnia, muscle cramps, fatigue,
      anorexia and syncope. Caution is advised in patients with bradycardia. Long-term
      use of donepezil in AD has been found to delay nursing-home placement and to
      result in caregiver respite. Donepezil also slows deterioration of cognition and
      global function in patients with moderate-to-severe AD, with improvement of
      abnormal behaviours. In addition to AD, donepezil demonstrates significant
      improvement in cognition, global function and activities of daily living in
      comparison with placebo-treated patients with vascular dementia and has potential
      therapeutic benefit for other neurological conditions.

PMID- 14680446
TI  - Valsartan for the treatment of heart failure.
AB  - Heart failure (HF) still has a discouraging prognosis. Therapeutic strategies aim
      to reduce mortality as well as slow the progression of the disease, improve
      symptoms and reduce the frequency of hospital admission. Activation of the renin
      angiotensin-aldosterone system (RAAS) is a hallmark of several cardiocirculatory
      diseases, including HF. Drugs for evidence-based therapy of HF are angiotensin
      converting enzyme inhibitors (ACEIs), beta-blockers and aldosterone antagonists.
      A promising alternative is a more complete action on the RAAS through selective
      blockade of the angiotensin type 1 (AT(1)) receptors, taking into account not
      only physiopathological issues but also pharmacological, experimental and
      clinical data. The effect of valsartan, an orally-active, selective antagonist of
      AT(1) receptors, on the outcome in patients with chronic and symptomatic HF was
      evaluated in a large-scale, international, placebo-controlled clinical study, the
      Valsartan in Heart Failure Trial (Val-HeFT). In this study, overall mortality was
      similar in the valsartan and placebo groups (19.7 and 19.4%, respectively).
      However, valsartan, in addition to recommended therapy of HF including an ACEI,
      significantly reduced the combined end point of mortality and morbidity, with a
      significant reduction in the risk of hospitalisation, paralleled by improvements
      in New York Heart Association (NYHA) functional class, signs and symptoms and
      quality of life. Valsartan also improved left ventricular anatomy and function
      and significantly reduced neurohormonal activation. These results were confirmed
      and extended by the CHARM trial, where the benefits of candesartan were proved
      not only in all 7599 patients with HF, but also in the 2548 given an ACEI, the
      2028 not given an ACEI and in the 3023 patients with an ejection fraction of >
      40%. In conclusion, the first choice for HF remains an ACEI with a beta-blocker,
      but two new options are emerging. In patients intolerant to ACEI, the combination
      of valsartan or candesartan with a beta-blocker is proposed, whereas an ACEI with
      either valsartan or candesartan can be considered in patients intolerant to or
      with contraindications to beta-blockers.

PMID- 14680447
TI  - Verteporfin ocular photodynamic therapy.
AB  - This article reviews the pharmacotherapeutics of verteporfin (Visudyne), Novartis
      Pharma AG) used in ocular photodynamic therapy. The chemistry, pharmacokinetics
      and pharmacodynamics of the drug are reviewed. The article highlights and
      summarises the results of the multi-centre, randomised, controlled clinical
      trials with verteporfin to treat subfoveal choroidal neovascularisation in age
      related macular degeneration, ocular histoplasmosis syndrome and pathologic
      myopia. In addition, the safety profile and side effects of verteporfin are
      discussed.

PMID- 14680448
TI  - Has COMET solved the controversy as to whether carvedilol is better than
      metoprolol in heart failure?
AB  - Carvedilol and metoprolol are beta(1)-adrenoceptor antagonists that decrease
      mortality in heart failure. It is not clear whether the ancillary properties,
      which carvedilol has but metoprolol does not have, contribute to the beneficial
      effect. The Carvedilol Or Metoprolol European Trial (COMET) compared metoprolol
      tartrate (mean daily dose 85 mg) and carvedilol (41.8 mg) in patients with heart
      failure. All-cause mortality was less in the carvedilol than the metoprolol
      group, indicating that at these doses, carvedilol has a mortality benefit over
      metoprolol. However, the beta(1)-adrenoceptor blocking activity of metoprolol
      tartrate (assessed by a decrease in heart rate) was slightly less than with
      carvedilol in COMET and less than that observed in previous mortality studies
      with metoprolol, suggesting that the use of metoprolol tartrate was not optimal
      in COMET.

PMID- 14680449
TI  - Cancer metastasis therapeutic targets and drug discovery: emerging small-molecule
      protein kinase inhibitors.
AB  - Cancer metastasis is a significant problem and a tremendous challenge to drug
      discovery relative to identifying key therapeutic targets as well as developing
      breakthrough medicines. Recent progress in unravelling the complex molecular
      circuitry of cancer metastasis, including receptors, intracellular proteins and
      genes, is highlighted. Furthermore, recent advances in drug discovery to provide
      novel proof-of-concept ligands, in vivo effective lead compounds and promising
      clinical candidates, are summarised. Such drug discovery efforts illustrate the
      integration of functional genomics, cell biology, structural biology, drug
      design, molecular/cellular screening and chemical diversity (e.g., small
      molecules, peptides/peptidomimetics, natural products, antisense, vaccines and
      antibodies). Promising therapeutic targets for cancer metastasis have been
      identified, including Src, focal adhesion kinase, the integrin receptor, the
      vascular endothelial growth factor receptor, the epidermal growth factor
      receptor, Her-2/neu, c-Met, Ras/Rac GTPases, Raf kinase, farnesyl diphosphate
      synthase (i.e., amino-bisphosphonate therapeutic target) and matrix
      metalloproteases within the context of their implicated functional roles in
      cancer growth, invasion, angiogenesis and survival at secondary sites. Clinical
      and preclinical drug discovery is described and emerging small-molecule
      inhibitors of protein kinases are highlighted.

PMID- 14680450
TI  - Histone deacetylase inhibitors in clinical development.
AB  - In addition to a variety of other novel agents, interest in histone deacetylase
      inhibitors (HDACIs) as antineoplastic drugs has recently accelerated and
      increasing numbers of these compounds have entered clinical trials in humans.
      HDACIs represent a prototype of molecularly targeted agents that perturb signal
      transduction, cell cycle-regulatory and survival-related pathways. Newer
      generation HDACIs have been introduced into the clinical arena that are
      considerably more potent on a molar basis than their predecessors and are
      beginning to show early evidence of activity, particularly in hematopoietic
      malignancies. In addition, there is an increasing appreciation of the fact that
      HDACIs may act through mechanisms other than induction of histone acetylation
      and, as in the case of other molecularly-targeted agents, it is conceivable that
      the ultimate role of HDACIs in cancer therapy will be as modulators of apoptosis
      induced by other cytotoxic agents. One particularly promising strategy involves
      attempts to combine HDACIs with other novel agents to promote tumour cell
      differentiation or apoptosis. The present review focuses on recent insights into
      the mechanisms by which HDACIs exert their anticancer effects, either alone or in
      combination with other compounds, as well as attempts to translate these findings
      into the clinic.

PMID- 14680451
TI  - Multimodal treatment strategies combining neoadjuvant hormonal therapy and/or
      chemotherapy with radical prostatectomy in high-risk localised prostate cancer.
AB  - By combining the readily available clinical parameters of tumour stage, Gleason
      score of the diagnostic biopsy specimen and serum prostate-specific antigen
      level, men with newly diagnosed prostate cancer can be assessed as to their risk
      of treatment failure after radiotherapy or radical prostatectomy. For men
      considered to be at high-risk of treatment failure after local therapy alone,
      multimodal treatment strategies may result in improved cancer-control outcomes.
      This strategy has proven effective in the setting of clinical stage T3 - T4
      tumours in which the combination of radiotherapy followed by hormonal therapy has
      improved patient survival. The benefit of neoadjuvant or adjuvant hormonal and/or
      chemotherapy followed by radical prostatectomy in this setting is unclear but is
      the subject of ongoing or planned Phase III clinical trials. These studies will
      help examine the role of multimodal treatment strategies in these high-risk
      patients.

PMID- 14680452
TI  - Diquafosol tetrasodium: a novel dry eye therapy.
AB  - The ophthalmic formulation of diquafosol tetrasodium (INS365), a P2Y2 receptor
      agonist, is targeted to treat dry eye disease through rehydration of the ocular
      surface. Existing pharmacological therapies for dry eye disease are limited,
      therefore, approval of this medication is anticipated. This review summarises key
      findings during development and in clinical trials including clinical
      effectiveness and safety. The relevance of P2Y2 receptor technology to dry eye
      disease and the disease process is discussed.

PMID- 14680453
TI  - Emtricitabine: a new nucleoside analogue for once-daily antiretroviral therapy.
AB  - Highly active antiretroviral therapy has resulted in a dramatic decline in
      morbidity and mortality among patients infected with HIV. Nevertheless, this
      success has to be considered in the context of the current challenges and needs
      in this field. Adherence, toxicity, potency and resistance are still matters of
      intense research, which need to improve in order to overcome the current
      limitations of available drugs. Regarding needs, the improvement of convenience,
      tolerability and pharmacokinetics run in parallel with toxicity reduction,
      improvement of activity (both for wild-type and resistant virus), penetration
      into viral reservoirs and exploitation of new targets. The Food and Drug
      Administration approved emtricitabine in July 2003 for use in combination with
      other antiretroviral agents in adults with HIV-1 infection. Approval was based on
      the results of two Phase III clinical trials. The first was a double-blind study
      comparing the safety and efficacy of emtricitabine + didanosine + efavirenz to
      stavudine + didanosine + efavirenz as initial treatment in individuals who had
      not previously received antiretroviral therapy. At 24 and 48 weeks, patients
      receiving emtricitabine had significantly higher rates of virological suppression
      and greater increases in CD4+ counts than stavudine recipients. The second study
      was an open-label trial in treatment-experienced patients with HIV RNA < 400
      copies/ml on a lamivudine-containing regimen in combination with either stavudine
      or zidovudine and either a protease inhibitor or a non-nucleoside reverse
      transcriptase inhibitor for at least 12 weeks. Patients were randomised either to
      continue lamivudine (150 mg b.i.d.) or to switch to emtricitabine 200 mg o.d.
      while maintaining the same background medications. In this study, the proportion
      of patients whose viral loads remained suppressed at the < 400 and < 50 copies/ml
      levels were similar in the two treatment groups. Potency, tolerability,
      convenient dosing and a low rate of side effects are some of the main
      characteristics of this new drug.

PMID- 14680454
TI  - The potential of activation of somatostatinergic neurotransmission with FK960 in
      Alzheimer's disease.
AB  - Somatostatin levels are reduced in post mortem brains of patients with
      Alzheimer's disease (AD). FK960 is a somatostatin-releasing agent. After oral
      administration to rhesus monkeys, FK960 is distributed to the entire brain. In
      patients with AD, regional cerebral blood flow and regional cerebral metabolic
      rate of glucose correlate with cognitive decline and the appearance of
      pathological changes. Aged rhesus monkeys are a good animal model of AD as they
      develop age-associated cognitive impairment. FK960 (1 mg/kg) caused modest
      increases in regional cerebral blood flow and regional cerebral metabolic rate of
      glucose in aged monkeys, suggesting that FK960 will improve cognition. Thus, the
      activation of somatostatinergic neurotransmission, with FK960 or a similar drug,
      has considerable potential in the treatment of cognitive impairment.

PMID- 14680455
TI  - 9th annual meeting of the Eating Disorders Research Society.
AB  - The application of modern neurobiological probes to the field of eating disorders
      has yielded new and exciting insights into the underlying mechanisms and causes
      of these devastating conditions. Findings from neuroimaging studies and genetic
      investigations have further confirmed and expanded our understanding of the role
      of the serotonin system in anorexia nervosa (AN) and bulimia nervosa. In
      addition, reduced regional cerebral blood flow in the temporal lobes and related
      brain structures have been identified in patients with AN, even after recovery.
      These data may hold promise for the development of more effective treatment
      strategies for these often chronic and refractory conditions. Results of reported
      treatment studies demonstrate the role and effectiveness of psychotherapy for AN
      and 'eating disorder not otherwise specified'; two eating disorders for which
      there is a paucity of empirically based treatments. Finally, more results from
      open studies of atypical antipsychotic medications in the treatment of AN are
      encouraging.

PMID- 14680456
TI  - Alzheimer's disease--current trends in basic and clinical research. Highlights
      from the 16th ECNP. September 20-24 2003, Prague, Czech Republic.

PMID- 14680457
TI  - Behavioural effects of the newer antiepileptic drugs: an update.
AB  - The negative and positive effects of the nine newer antiepileptic drugs that have
      received a product licence in the UK or in the US are reviewed. The importance of
      avoiding misinterpretation of the data because of confounding factors such as
      alternative psychosis, the release phenomenon or drug interactions is emphasised.
      Vigabatrin has been associated with both psychosis and depression. Due to the
      concentric visual field defects that may occur with vigabatrin, its use is now
      limited, although it remains the drug of choice for infantile spasms. Lamotrigine
      seems to be largely associated with improvement rather than deterioration of mood
      and behaviour. It may have a role in treating affective disorder. Gabapentin
      probably has relatively little effect on behaviour but may exacerbate behavioural
      problems in some children with pre-existing difficulties. Topiramate may
      precipitate both psychosis and depression, but these are less likely to occur if
      the currently recommended lower starting doses, escalation rates and target doses
      are used. The data for tiagabine are limited, but there is no clear evidence for
      psychosis or depression being caused by this drug. Oxcarbazepine may be of value
      in treating mood disorder, but the information is very limited. There are few
      reports of behavioural disturbances with levetiracetam, but the data suggest that
      there is no significant increase in psychosis or depression. There are some
      reports of psychosis and other behavioural disturbances with felbamate, but the
      use of this drug is limited by the serious adverse effects of hepatotoxicity and
      aplastic anaemia. There is some evidence for psychosis with zonisamide, but there
      is also a suggestion that this drug may be of benefit in treating psychiatric
      disorders. Careful individual assessment of each patient should enable the
      clinician to determine whether the medication or some other factor is responsible
      for any behavioural disturbance.

PMID- 14680458
TI  - Can dual blockade of the renin-angiotensin system reduce progression of kidney
      disease beyond monotherapy?
AB  - It is well-accepted that therapies directed at the renin-angiotensin system (RAS)
      reduce the progression of chronic kidney disease. Angiotensin-converting enzyme
      (ACE) inhibitors and the angiotensin receptor blockers (ARBs) are currently
      available to interrupt this cascade. Their positive actions result from better
      blood pressure control, a reduction in glomerular capillary pressure and a
      decrease in proteinuria. Blockade of the RAS may also reduce renal scarring by
      blunting direct pro-fibrotic effects of angiotensin II and aldosterone. Although
      these drugs successfully reduce urinary protein excretion and improve renal
      survival, a significant number of patients continue to progress to end stage
      renal disease. It is possible, however, that dual blockade of the RAS with an ACE
      inhibitor and an ARB might offer further benefit beyond using either agent alone.
      Optimally, the goal should be to completely halt the progression of kidney
      disease. With these concepts in mind, this paper will review the RAS and its
      effects on the kidney. The efficacy and safety of dual RAS blockade in
      proteinuric renal diseases will be examined. Finally, recommendations for
      utilising combined therapy with ACE inhibitors and ARBs will be provided.

PMID- 14680459
TI  - The safety of antihypertensives for treatment of pregnancy hypertension.
AB  - This review addresses the maternal and perinatal benefits and risks of
      antihypertensive therapy in pregnancy. It covers the diagnosis of hypertension in
      pregnancy (with a brief discussion of ambulatory blood pressure measurement)
      followed by both the general principles of management of pregnancy hypertension
      and the specifics of individual antihypertensive drugs and drug classes.
      Discussion is focused on quantitative overviews of randomised, controlled trials,
      although observational literature is also discussed, particularly in reference to
      the potential teratogenicity of agents and the safety of their administration to
      nursing mothers. The treatment of severe hypertension is addressed separately
      from the treatment of mild-to-moderate hypertension, for which the maternal and
      fetal risks are substantially different.

PMID- 14680460
TI  - Safety of GnRH agonists and antagonists.
AB  - The widespread application of protocols using gonadotropin-releasing hormone
      (GnRH) agonists or antagonists in assisted reproduction treatment has led to an
      increasing number of pregnancies exposed to these drugs. This issue has raised
      scepticism as to the safety of these medications, concerning both pregnant women
      and their offspring. The main parameters that can be studied to ensure the safety
      of GnRH analogues include: a) systemic and local reactions to the medication; b)
      incidence of ovarian hyperstimulation syndrome (OHSS); c) direct effect on
      oocytes and embryos; and d) the health of those children exposed. So far, no
      systemic side effects and no major local reactions have been reported following
      the use of GnRH agonists or third-generation antagonists. On the other hand, the
      incidence of OHSS seems to be higher with GnRH agonist protocols compared to
      conventional or GnRH antagonist protocols. The recent cloning of the GnRH
      receptor has led to the demonstration of GnRH receptor gene expression in the
      human ovary, although the existence of GnRH receptors per se remains
      controversial. Similarly, the potential direct effect of GnRH analogues on the
      follicles and oocytes remains a matter of debate. The incidence of miscarriage
      and the health of children born as a result of in vitro fertilisation (IVF)
      treatment do not appear to be influenced by the GnRH agonist treatment. This also
      seems to be the case for the GnRH antagonists, although the available information
      on this issue is still limited. Therefore, most of the accumulated data
      concerning the safety of the GnRH analogues are encouraging, and no serious side
      effects have been reported. On the other hand, as no definite conclusions about
      the safety of these drugs can be drawn until now, continued assessment of the
      aforementioned parameters in long-term follow-up studies is recommended.

PMID- 14680461
TI  - Thalidomide: an old drug with new clinical applications.
AB  - Thalidomide has several targets and mechanisms of action: a hypnosedative effect,
      several immunomodulatory properties with an effect on the production of TNF-alpha
      and the balance between the different lymphocyte subsets and an antiangiogenic
      action. Thalidomide has been used in several cutaneous inflammatory disorders
      (e.g., erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus
      erythematosus and severe aphtosis), cancers (e.g., relapsed/refractory multiple
      myeloma, malignant melanoma and systemic signs in cancer) and inflammatory
      conditions (e.g., Crohn's disease and rheumatoid arthritis). Several side effects
      are associated with thalidomide. Some are major, such as teratogenicity,
      peripheral neuropathy and deep vein thrombosis. Somnolence and rash are
      frequently reported when thalidomide is used at higher doses as an
      anticarcinogenic agent and can lead to dose reduction or treatment
      discontinuation depending on severity. Minor side effects include abdominal pain
      and endocrine disturbances. To prevent the teratogenicity, use of thalidomide is
      strictly controlled in western countries with close adherence to a birth control
      programme. Close monitoring for early development of peripheral neuropathy is
      also recommended.

PMID- 14680462
TI  - Drug-induced nail abnormalities.
AB  - A large number of drugs may be responsible for the development of nail changes,
      including cancer chemotherapeutic agents and retinoids, however, only a few
      classes of drugs are consistently associated with nail symptoms. Drug-induced
      nail abnormalities result from toxicity to the matrix, the nail bed, the
      periungual tissues or the digit blood vessels. The most common symptoms include
      Beau's lines, onychomadesis, melanonychia, onycholysis and periungual pyogenic
      granulomas. Drug-induced nail changes usually involve several or all of the
      nails. In most cases, nail abnormalities are asymptomatic, but can sometimes
      cause pain and impair manual activities.

PMID- 14680463
TI  - Hypotonic intravenous solutions in children.
AB  - The use of hypotonic intravenous solutions, especially 4% dextrose/0.18% saline,
      remains standard practice in many paediatric units in the UK. The practice of
      prescribing hypotonic intravenous fluids derives from the work of investigators
      in the 1950s, who produced arbitrarily-derived formulae for calculating the
      maintenance requirements for water and electrolytes in hospitalised patients.
      Combining these values led to the widespread acceptance of hypotonic solutions
      such as 4% dextrose/0.18% saline as 'standard maintenance' parenteral fluids.
      Unfortunately, these calculations do not account for the effects of antidiuretic
      hormone, the secretion of which is stimulated by many factors encountered during
      acute illness and especially in the perioperative period. In this setting, the
      administration of hypotonic intravenous fluids results in the retention of free
      water and the development of hyponatraemia. The routine administration of
      hypotonic intravenous fluids has been shown to be associated with severe
      morbidity and the deaths of many previously healthy children. The problem is
      compounded by the fact that 4% dextrose/0.18% saline is labelled as 'isotonic'.
      Whilst this solution is isosmolar compared to plasma, lack of osmotically
      effective solutes means that it is hypotonic with reference to the cell membrane.
      There is no justification for the routine administration of hypotonic intravenous
      fluids.

PMID- 14680464
TI  - Stem cell therapy for muscular dystrophy.
AB  - Muscular dystrophy is a heterogeneous group of neuromuscular disorders that
      manifests as progressive muscle weakness, muscle wasting and, in many cases,
      death. Although there has been enormous progress in the molecular understanding
      of muscular dystrophy, there is still no cure. There are, however, several
      different therapeutic options under investigation, including adult-derived stem
      cell transplantation. Encouraging and pioneering experiments in mouse models for
      Duchenne's muscular dystrophy (DMD) demonstrated that myoblasts could be
      transplanted into dystrophic muscle; these myoblasts repaired a small proportion
      of damaged myofibres. Subsequent work has been devoted to optimisation of this
      technique. In doing so, a number of adult-derived stem cells have been isolated,
      characterised and used in promising animal transplantation experiments. Further
      research is ongoing, and is clearly necessary to make this therapy a viable
      treatment option for patients with muscular dystrophy.

PMID- 14680465
TI  - T cell-based therapies for EBV-associated malignancies.
AB  - Epstein-Barr virus (EBV) is associated with a number of human malignancies. The
      cells of these tumours express a range of EBV latent cycle gene products that
      have the potential to be exploited as targets for T cell-mediated immunological
      therapies. Considerable progress has been made in developing adoptive T cell
      transfer for EBV-associated post-transplant lymphoproliferative disease (PTLD)
      and clinical experience clearly demonstrates that EBV-specific T cell responses
      can be used to treat this EBV-associated malignancy. Adoptive T cell therapies
      for other EBV-associated malignancies are less advanced, although encouraging
      data are starting to emerge. Adoptive T cell transfer, however, does require
      significant levels of specialist laboratory support. Large-scale treatment of
      patients in geographical areas with a high prevalence of EBV-associated
      malignancy is likely to require the development of therapeutic vaccination
      strategies, a number of which are in development at present. Although it remains
      to be seen whether long-lasting sterilising immunity to EBV could be achieved, an
      alternative vaccine-based approach would be to develop a prophylactic vaccine to
      protect against primary EBV infection.

PMID- 14680466
TI  - Dry powder inhalers for optimal drug delivery.
AB  - Dry powder inhalers (DPIs) have been available for delivering drugs to the lungs
      for over 30 years. In the last decade there has been a big increase in DPI
      development, resulting partly from recognised limitations in other types of
      inhaler device. Many companies are developing DPIs for asthma and chronic
      obstructive pulmonary disease (COPD) therapy, and there is increasing recognition
      of the potential role of DPI systems for other therapies, such as inhaled
      antibiotics and peptides/proteins. Optimised drug delivery may be achieved not
      only by improvements to devices, but also via more sophisticated formulations
      that disperse easily in the inhaled air-stream and which may often be delivered
      by relatively simple inhaler devices. DPIs could become the device category of
      choice for a wide range of inhaled therapies, involving both local and systemic
      drug delivery.

PMID- 14680467
TI  - Microspheres for controlled release drug delivery.
AB  - Controlled release drug delivery employs drug-encapsulating devices from which
      therapeutic agents may be released at controlled rates for long periods of time,
      ranging from days to months. Such systems offer numerous advantages over
      traditional methods of drug delivery, including tailoring of drug release rates,
      protection of fragile drugs and increased patient comfort and compliance.
      Polymeric microspheres are ideal vehicles for many controlled delivery
      applications due to their ability to encapsulate a variety of drugs,
      biocompatibility, high bioavailability and sustained drug release
      characteristics. Research discussed in this review is focused on improving large
      scale manufacturing, maintaining drug stability and enhancing control of drug
      release rates. This paper describes methods of microparticle fabrication and the
      major factors controlling the release rates of encapsulated drugs. Furthermore,
      recent advances in the use of polymer microsphere-based systems for delivery of
      single-shot vaccines, plasmid DNA and therapeutic proteins are discussed, as well
      as some future directions of microsphere research.

PMID- 14680468
TI  - Parvovirus vectors for cancer gene therapy.
AB  - Parvoviruses comprise a group of single-stranded DNA viruses with greater
      potential for gene therapy applications. Unique characteristics of paroviruses,
      such as non-pathogenicity, antioncogenicity and methods of efficient recombinant
      vector production, have drawn more attention towards utilising parvovirus-based
      vectors in cancer gene therapy. Although > 30 different parvoviruses have been
      identified so far, recombinant vectors derived from adeno-associated virus (AAV),
      minute virus of mice (MVM), LuIII and parvovirus H1 have been successfully tested
      in many preclinical models of human diseases, including cancer. The present
      article will focus on the potential of non-replicating and autonomously
      replicating parvoviral vectors in cancer gene therapy, including strategies that
      target tumour cells directly or indirectly.

PMID- 14680469
TI  - Strategies for targeting protein therapeutics to selected tissues and cells.
AB  - The advent of recombinant biotechnology and the recent sequencing of the human
      genome now allow for identification of scores of potential protein therapeutics
      along with the capacity to produce them in quantities and purities required for
      clinical application. Thus, clinical development of potential protein
      therapeutics has become as commonplace as development efforts of classical small
      molecule therapeutics. Whereas small molecule therapeutic lead candidates are
      identified through screens of large sets of possibilities, therapeutic protein
      candidates are defined by genetic information as a single composition (or a
      limited set of isoforms). Small molecule leads are identified through the
      combined assessment of desired selectivity, biodistribution and pharmacokinetic
      properties. In essence, these selection parameters emulate the actions of protein
      therapeutics that function as systemic hormones through their ability to target
      selective cells and tissues of the body via selective receptor interaction with
      minimal actions elsewhere. However, many, if not most, potential protein
      therapeutics do not normally circulate through the body to reach their target
      cell or tissue; rather, they are frequently synthesised at local sites, act at
      that site and are degraded without reaching appreciable systemic levels. Dose
      limiting adverse events are associated with systemic administration of many of
      these proteins, restricting their clinical potential. This review examines
      current strategies to reduce these dose-limiting events by possibly focusing the
      delivery of potential protein therapeutics to discrete tissues and cells.

PMID- 14680470
TI  - Antisense oligonucleotide treatments for psoriasis.
AB  - Antisense oligonucleotides are emerging as an exciting therapeutic strategy for
      treating skin diseases such as psoriasis. Potential antisense targets are
      proteins upregulated in psoriatic skin, in particular those associated with
      inflammation (intercellular adhesion molecule [ICAM]-1, IL-2 and -8),
      proliferation (insulin-like growth factor type I receptor [IGF-IR], epidermal
      growth factor) and hyperangiogenesis (vascular endothelial growth factor [VEGF]).
      Whereas topical application and subsequent penetration of large oligonucleotides
      into normal skin is problematic, the impaired barrier function of psoriatic
      lesions permits the uptake of antisense drugs. Studies to date indicate that
      topically applied antisense molecules can be delivered to target cells in the
      epidermis and dermis of psoriatic skin. Antisense-mediated suppression of target
      mRNA and protein has been demonstrated in models of human skin grafted to
      immunosuppressed mice and in hairless mouse models of skin inflammation. In a
      xenograft model of human psoriasis, treatment with repeated intradermal
      injections of IGF-IR antisense caused a normalisation of the epidermal
      hyperproliferation. This class of drug, therefore, holds much potential for the
      successful treatment of psoriasis in the clinical setting.

PMID- 14680471
TI  - Use of proteomic analysis to monitor responses to biological therapies.
AB  - Proteomics has the potential to revolutionise diagnosis and disease management.
      Serum protein pattern profiling by surface-enhanced laser desorption/ionisation
      time of flight (SELDI-TOF) mass spectrometry is emerging as a novel approach to
      discover protein patterns capable of distinguishing disease and disease-free
      states with high sensitivity and specificity. This method has shown great promise
      for early diagnosis of ovarian cancer and is being applied to a range of
      pathological states. Protein microarray technology is being evaluated as a new
      means to track biological responses to therapy. Through the measurement of key
      protein phosphorylation sites at different stages of disease progression or
      before and after treatment, protein signal pathways can be mapped and thus become
      the starting point for individualised therapy. Laser capture microdissection
      (LCM) coupled with immunostaining of protein microarrays allows isolation of pure
      cell populations and relative quantitation of phosphorylated and non
      phosphorylated forms of the cell's key signalling proteins. This technology is
      currently in use at the National Institutes of Health in Phase II clinical trials
      of metastatic breast and ovarian cancer. Cell survival and apoptotic protein
      pathways are monitored as biological markers of disease progression in these
      clinical trials. Proteomic technologies, such as serum protein pattern profiling,
      combined with protein microarray technologies, constitute a new paradigm for
      detecting disease and monitoring disease response to therapy. Ultimately,
      proteomics and genomics will become integrated into cancer patient management
      through the design and tracking of individualised therapy.

PMID- 14680472
TI  - Antibody-based treatment of acute myeloid leukaemia.
AB  - Monoclonal antibodies have become an important treatment modality in cancer
      therapy. Genetically engineered chimaeric and humanised antibodies have
      demonstrated activity against a variety of tumours. Whereas the humanised anti
      CD33 monoclonal antibody HuM195 has only modest activity against overt acute
      myeloid leukaemia (AML), it can eliminate minimal residual disease detectable by
      reverse transcription-polymerase chain reaction in acute promyelocytic leukaemia.
      High-dose radioimmunotherapy with beta-particle-emitting isotopes targeting CD33,
      CD45 and CD66 can potentially allow intensification of antileukaemic therapy
      before bone marrow transplantation. Conversely, alpha-particle immunotherapy with
      isotopes such as bismuth-213 or actinium-225 offers the possibility of selective
      tumour cell kill while sparing surrounding normal cells. Targeted chemotherapy
      with the anti-CD33-calicheamicin construct gemtuzumab ozogamicin has produced
      remissions as a single agent in patients with relapsed AML and appears promising
      when used in combination with standard chemotherapy in the treatment of newly
      diagnosed AML.

PMID- 14680473
TI  - 18th Annual Scientific Meeting of the International Society for Biological
      Therapy of Cancer. 30 October-2 November 2003, Bethesda, Maryland, USA.
AB  - The 18th Annual Scientific Meeting of the International Society for Biological
      Therapy of Cancer (iSBTc) was held at the Hyatt Regency, Bethesda, MD, close to
      the National Institutes of Health (NIH) campus. The meeting was organised on
      behalf of the society by Neil Berinstein from Aventis Pasteur, Toronto, Canada,
      Janice P Dutcher from Our Lady of Mercy Medical Center, Bronx, NY and Francesco M
      Marincola from the NIH, Bethesda, MD. The 2003 meeting included 57 oral
      presentations and > 100 poster presentations. There were > 800 registrants to the
      Annual Meeting and the multiple satellite symposia. The iSBTc, formerly the
      Society of Biological Therapy (SBT), was founded by R Oldham in 1984. Its
      membership has been rapidly growing of late, with > 500 members at present. The
      purpose of the iSBTc is to bring together those diverse individuals actively
      investigating biologic agents and biological response modifiers in the treatment
      of cancer, including clinicians and basic scientists from industry, government
      and academia. The President of the Society is Dr Michael B Atkins from Beth
      Israel Deaconess Medical Center, Boston, MA and the Vice President is Ulrich
      Keilholz from UKBF, Free University Berlin, Germany.

PMID- 14680474
TI  - Ubiquinone is not required for proton conductance by uncoupling protein 1 in
      yeast mitochondria.
AB  - Q (coenzyme Q or ubiquinone) is reported to be a cofactor obligatory for proton
      transport by UCPs (uncoupling proteins) in liposomes [Echtay, Winkler and
      Klingenberg (2000) Nature (London) 408, 609-613] and for increasing the binding
      of the activator retinoic acid to UCP1 [Tomas, Ledesma and Rial (2002) FEBS Lett.
      526, 63-65]. In the present study, yeast ( Saccharomyces cerevisiae ) mutant
      strains lacking Q and expressing UCP1 were used to determine whether Q was
      required for UCP function in mitochondria. Wild-type yeast strain and two mutant
      strains (CENDeltaCOQ3 and CENDeltaCOQ2), both not capable of synthesizing Q, were
      transformed with the mouse UCP1 gene. UCP1 activity was measured as fatty acid
      dependent, GDP-sensitive proton conductance in mitochondria isolated from the
      cells. The activity of UCP1 was similar in both Q-containing and -deficient yeast
      mitochondria. We conclude that Q is neither an obligatory cofactor nor an
      activator of proton transport by UCP1 when it is expressed in yeast mitochondria.

PMID- 14680475
TI  - Identification of glycogen synthase as a new substrate for stress-activated
      protein kinase 2b/p38beta.
AB  - The endogenous glycogen synthase in extracts from mouse skeletal muscle, liver
      and brain bound specifically to SAPK2b (stress-activated protein kinase 2b)/p38b,
      but not to other members of the group of SAPK/p38 kinases. Glycogen synthase was
      phosphorylated in vitro more efficiently by SAPK2b/p38b than by SAPK2a/p38a,
      SAPK3/p38g or SAPK4/p38d. SAPK2b/p38b phosphorylated glycogen synthase in vitro
      at residues Ser644, Ser652, Thr718 and Ser724, two of which (Ser644 and Ser652)
      are also phosphorylated by glycogen synthase kinase 3. Thr718 and Ser724 are
      novel sites not known to be phosphorylated by other protein kinases. Glycogen
      synthase becomes phosphorylated at Ser644 in response to osmotic shock; this
      phosphorylation is prevented by pretreatment of the cells with SB 203580, which
      inhibits SAPK2a/p38a and SAPK2b/p38b activity. In vitro, phosphorylation of
      glycogen synthase by SAPK2b/p38b alone had no significant effect on its activity,
      indicating that phosphorylation at residue Ser644 itself is insufficient to
      decrease glycogen synthase activity. However, after phosphorylation by
      SAPK2b/p38b, subsequent phosphorylation at Ser640 by glycogen synthase kinase 3
      decreased the activity of glycogen synthase. This decrease was not observed when
      SAPK2b/p38b activity was blocked with SB 203580. These results suggest that
      SAPK2b/p38b may be a priming kinase that allows glycogen synthase kinase 3 to
      phosphorylate Ser640 and thereby inhibit glycogen synthase activity.

PMID- 14680476
TI  - Expression of YAP4 in Saccharomyces cerevisiae under osmotic stress.
AB  - YAP4, a member of the yeast activator protein ( YAP ) gene family, is induced in
      response to osmotic shock in the yeast Saccharomyces cerevisiae. The null mutant
      displays mild and moderate growth sensitivity at 0.4 M and 0.8 M NaCl
      respectively, a fact that led us to analyse YAP4 mRNA levels in the hog1 (high
      osmolarity glycerol) mutant. The data obtained show a complete abolition of YAP4
      gene expression in this mutant, placing YAP4 under the HOG response pathway. YAP4
      overexpression not only suppresses the osmosensitivity phenotype of the yap4
      mutant but also relieves that of the hog1 mutant. Induction, under the conditions
      tested so far, requires the presence of the transcription factor Msn2p, but not
      of Msn4p, as YAP4 mRNA levels are depleted by at least 75% in the msn2 mutant.
      This result was further substantiated by the fact that full YAP4 induction
      requires the two more proximal stress response elements. Furthermore we find that
      GCY1, encoding a putative glycerol dehydrogenase, GPP2, encoding a NAD-dependent
      glycerol-3-phosphate phosphatase, and DCS2, a homologue to a decapping enzyme,
      have decreased mRNA levels in the yap4 -deleted strain. Our data point to a
      possible, as yet not entirely understood, role of the YAP4 in osmotic stress
      response.

PMID- 14680477
TI  - A proximal tissue-specific module and a distal negative regulatory module control
      apolipoprotein(a) gene transcription.
AB  - The apo(a) [apolipoprotein(a)] gene is responsible for variations in plasma
      lipoprotein(a), high levels of which are a risk factor for atherosclerosis and
      myocardial infarction. The apo(a) promoter stimulates the expression of reporter
      genes in HepG2 cells, but not in HeLa cells. In the present study, we demonstrate
      that the 1.4 kb apo(a) promoter comprises two composite regulatory regions: a
      distal negative regulatory module (positions -1432 to -716) and a proximal tissue
      specific module (-716 to -616). The distal negative regulatory module contains
      two strong negative regulatory regions [polymorphic PNR (pentanucleotide repeat
      region) and NREbeta (negative regulatory element beta)], which sandwich the
      postive regulatory region PREbeta (positive regulatory element beta). The PNR was
      shown to bind to transcription factors in a tissue-specific manner, whereas the
      ubiquitous transcription factors hepatocyte nuclear factor 3alpha and GATA
      binding protein 4 bound to NREbeta to repress gene transcription. The proximal
      tissue-specific module contains two regulatory elements: an activating region
      (PREalpha) that activates transcription in HepG2 cells, and NREalpha, which is
      responsible for repressing the apo(a) gene in HeLa cells. NREalpha binds to a
      HeLa-specific repressor. These multiple regulatory elements might work co
      operatively to finely regulate apo(a) gene expression. Although the tissue
      specific module is required for apo(a) gene activation and repression in a tissue
      specific manner, the combinatorial interplay of the distal and proximal
      regulators might define the complex pathway(s) of apo(a) gene regulation.

PMID- 14680478
TI  - Proline residues in transmembrane segment IV are critical for activity,
      expression and targeting of the Na+/H+ exchanger isoform 1.
AB  - NHE1 (Na+/H+ exchanger isoform 1) is a ubiquitously expressed integral membrane
      protein that regulates intracellular pH in mammalian cells. Proline residues
      within transmembrane segments have unusual properties, acting as helix breakers
      and increasing flexibility of membrane segments, since they lack an amide
      hydrogen. We examined the importance of three conserved proline residues in TM IV
      (transmembrane segment IV) of NHE1. Pro167 and Pro168 were mutated to Gly, Ala or
      Cys, and Pro178 was mutated to Ala. Pro168 and Pro178 mutant proteins were
      expressed at levels similar to wild-type NHE1 and were targeted to the plasma
      membrane. However, the mutants P167G (Pro167-->Gly), P167A and P167C were
      expressed at lower levels compared with wild-type NHE1, and a significant portion
      of P167G and P167C were retained intracellularly, possibly indicating induced
      changes in the structure of TM IV. P167G, P167C, P168A and P168C mutations
      abolished NHE activity, and P167A and P168G mutations caused markedly decreased
      activity. In contrast, the activity of the P178A mutant was not significantly
      different from that of wild-type NHE1. The results indicate that both Pro167 and
      Pro168 in TM IV of NHE1 are required for normal NHE activity. In addition,
      mutation of Pro167 affects the expression and membrane targeting of the
      exchanger. Thus both Pro167 and Pro168 are strictly required for NHE function and
      may play critical roles in the structure of TM IV of the NHE.

PMID- 14680479
TI  - Regulation of mammary gland branching morphogenesis by the extracellular matrix
      and its remodeling enzymes.
AB  - A considerable body of research indicates that mammary gland branching
      morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM
      receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes,
      including matrix metalloproteinases (MMPs) and their inhibitors, tissue
      inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM
      cues affect one or more of the following processes: cell survival, polarity,
      proliferation, differentiation, adhesion, and migration. Both three-dimensional
      culture models and genetic manipulations of the mouse mammary gland have been
      used to study the signaling pathways that affect these processes. However, the
      precise mechanisms of ECM-directed mammary morphogenesis are not well understood.
      Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process
      akin to invasion by breast cancer cells, although the former is a highly
      regulated developmental process. How these morphogenic pathways are integrated in
      the normal gland and how they become dysregulated and subverted in the
      progression of breast cancer also remain largely unanswered questions.

PMID- 14680481
TI  - Deregulation of p27 by oncogenic signaling and its prognostic significance in
      breast cancer.
AB  - p27 is a key regulator of progression from G1 to S phase. Although the gene
      encoding p27 is rarely mutated in human cancers, p27 is functionally inactivated
      in a majority of human cancers through accelerated p27 proteolysis, through
      sequestration by cyclin D-cyclin-dependent kinase complexes and by cytoplasmic
      mislocalization. Here we review mechanisms whereby oncogenic activation of
      receptor tyrosine kinase and Ras pathways lead to accelerated p27 proteolysis and
      p27 mislocalization in cancer cells. The prognostic significance of p27 in human
      breast cancer is also reviewed.

PMID- 14680482
TI  - Models of breast cancer: is merging human and animal models the future?
AB  - Survival rates of patients with early breast cancer in the United Kingdom and in
      the United States have improved steadily over the past 15 years. The only way to
      continue or even accelerate this progress, however, is the discovery and
      development of new preventative and therapeutic strategies. With the massive
      explosion in potential therapeutic strategies becoming available, in the
      postgenomic era, better and more representative breast cancer models are urgently
      required for preclinical trials. Development of better in vivo models of human
      breast cancer are thus of crucial importance in the development of new cancer
      therapeutics.

PMID- 14680483
TI  - Models of breast cancer: quo vadis, animal modeling?
AB  - Rodent models for breast cancer have for many decades provided unparalleled
      insights into cellular and molecular aspects of neoplastic transformation and
      tumorigenesis. Despite recent improvements in the fidelity of genetically
      engineered mice, rodent models are still being criticized by many colleagues for
      not being 'authentic' enough to the human disease. Motives for this criticism are
      manifold and range from a very general antipathy against the rodent model system
      to well-founded arguments that highlight physiological variations between
      species. Newly proposed differences in genetic pathways that cause cancer in
      humans and mice invigorated the ongoing discussion about the legitimacy of the
      murine system to model the human disease. The present commentary intends to
      stimulate a debate on this subject by providing the background about new
      developments in animal modeling, by disputing suggested limitations of
      genetically engineered mice, and by discussing improvements but also ambiguous
      expectations on the authenticity of xenograft models to faithfully mimic the
      human disease.

PMID- 14680485
TI  - Introducing the concept of breast cancer stem cells.

PMID- 14680486
TI  - Akt2: a role in breast cancer metastasis.
AB  - Metastasis in breast cancer significantly increases morbidity and mortality. The
      5-year survival rate reduces from 90% for localised disease to about 20% once
      metastasis has taken place. The phosphoinositide 3-kinase/Akt signalling pathway
      has an important role in cell motility, invasion and metastasis. However, the
      precise contribution of the Akt kinase family members, Akt1, Akt2 and Akt3, in
      mediating these processes is unclear. The possibility that they have distinct
      functions in tumour progression is particularly interesting.

PMID- 14680487
TI  - 8th Nottingham International Breast Cancer Conference, Nottingham, UK, 16-19
      September 2003.
AB  - The four-day biennial 8th Nottingham Breast Cancer Conference held at the East
      Midlands Conference Centre, University of Nottingham, UK (16-19 September 2003)
      once again proved to be a successful event. Recent advances in clinical and
      scientific research were presented to an international audience, covering a broad
      spectrum of breast cancer issues including prediction, diagnosis and treatment.
      Delegates were encouraged to participate in workshop sessions, which allowed the
      comprehensive discussion of existing and promising future advances in breast
      cancer care.

PMID- 14680484
TI  - Advances in estrogen receptor biology: prospects for improvements in targeted
      breast cancer therapy.
AB  - Estrogen receptor (ER) has a crucial role in normal breast development and is
      expressed in the most common breast cancer subtypes. Importantly, its expression
      is very highly predictive for response to endocrine therapy. Current endocrine
      therapies for ER-positive breast cancers target ER function at multiple levels.
      These include targeting the level of estrogen, blocking estrogen action at the
      ER, and decreasing ER levels. However, the ultimate effectiveness of therapy is
      limited by either intrinsic or acquired resistance. Identifying the factors and
      pathways responsible for sensitivity and resistance remains a challenge in
      improving the treatment of breast cancer. With a better understanding of
      coordinated action of ER, its coregulatory factors, and the influence of other
      intracellular signaling cascades, improvements in breast cancer therapy are
      emerging.

PMID- 14680488
TI  - Radiotherapeutic use of 2-deoxy-2-[18F]fluoro-D-glucose--a comment.

PMID- 14680489
TI  - The diagnosis and management of pre-invasive breast disease: another point of
      view.

PMID- 14680491
TI  - AACR Special Conference: Advances in Breast Cancer Research--Genetics, Biology,
      and Clinical Implications, Huntington Beach, California, USA, 8-12 October 2003.
AB  - The recent meeting 'Advances in Breast Cancer Research--Genetics, Biology, and
      Clinical Implications' was an American Association for Cancer Research (AACR)
      Special Conference in Cancer Research, for which the underwriting sponsor was the
      Avon Foundation. Presentations were made from prominent scientists on several
      relevant basic science and clinic-oriented topics, including mammary stem cells
      and development, steroid receptors, matrix and stromal-epithelial interactions,
      oncogene signaling and imaging, genetics and prevention, and molecular
      therapeutics. A summary of recent findings is presented here, with a particular
      emphasis on unpublished work.

PMID- 14680492
TI  - Are BRCA1- and BRCA2-related breast cancers associated with increased mortality?
AB  - There has been contradictory evidence as to whether BRCA1 associated breast
      cancers have a poorer prognosis than non-BRCA1 cancers. In this issue of Breast
      Cancer Research Robson and colleagues provide further evidence for poorer
      survival in BRCA1 carriers and show that it could be attributed to failure to
      treat small node-negative grade 3 breast cancers with chemotherapy. There still
      remains little evidence for a survival difference for BRCA2 related breast
      cancers. Although the high contralateral breast cancer risk is confirmed by this
      study there is no real evidence for an increase in ipsilateral recurrence or new
      primary breast cancers in mutation carriers up to the 10-year point.

PMID- 14680493
TI  - Prevention of breast cancer by recapitulation of pregnancy hormone levels.
AB  - At the present time, the only approved method of breast cancer prevention is use
      of the selective estrogen receptor modulator (SERM) tamoxifen. Many breast
      cancers are driven to grow by estrogen, and tamoxifen exploits this by blocking
      estrogen action at the estrogen receptor. A counter-intuitive and controversial
      approach to breast cancer prevention is administration of estrogen and progestin
      at an early age to achieve pregnancy levels. This approach is supported by the
      fact that breast cancer incidence is halved by early (< or = 20 years of age)
      full-term pregnancy. Moreover, it has been demonstrated in rodent models that
      mimicking the hormonal milieu can effectively prevent carcinogen-induced mammary
      cancer. In this issue of Breast Cancer Research Rajkumar and colleagues use the
      rodent model to further define the timing and type of hormonal therapy that is
      effective in preventing mammary carcinogenesis. Clearly, application of this
      approach in humans may be difficult, but the potential benefit is intriguing.

PMID- 14680494
TI  - Interleukin-2 and its receptor complex (alpha, beta and gamma chains) in in situ
      and infiltrative human breast cancer: an immunohistochemical comparative study.
AB  - INTRODUCTION: The presence and distribution of interleukin-2 (IL-2) and its
      receptor complex (Ralpha, Rbeta, Rgamma) were studied in 52 women who were
      clinically and histopathologically diagnosed with breast tumours (17 in situ and
      35 infiltrating), and in 13 women with benign fibrocystic lesions in the breast.
      METHODS: Immunohistochemistry with antibodies against IL-2, IL-2Ralpha, IL-2Rbeta
      and IL-2Rgamma was used. A comparative semiquantitative immunohistochemical study
      between the three breast groups (fibrocystic lesions, in situ tumours and
      infiltrating tumours) was performed. RESULTS: IL-2 and its three receptor chains
      were immunodetected in the cytoplasm of epithelial cells. The three receptor
      chains were also detected on the cell surface. In fibrocystic lesions,
      immunoreactions to IL-2 (38.5% of cases), IL-2Ralpha (53.8%) and IL-2Rbeta
      (30.8%) were very weak, whereas immunoreaction to IL-2Rgamma (46.1%) was somewhat
      more intense. In in situ tumours, the percentages of cases that immunostained
      positively for IL-2 and its three receptor chains were similar to those observed
      in fibrocystic lesions, but immunostainings of the four antibodies were more
      intense. In infiltrative tumours, the percentages of positively stained cases and
      also immunostaining intensities were approximately twice that found for in situ
      tumours. Within infiltrating tumours, the percentage of cases showing
      immunoreaction to IL-2 and their three receptor chains was higher in the patients
      with lymph node infiltration at the time of surgery. CONCLUSION: The development
      of breast tumour is associated with an increased expression of IL-2 and its three
      receptor chains, and this expression also seems to be associated with the
      malignancy of the tumour.

PMID- 14680495
TI  - A combined analysis of outcome following breast cancer: differences in survival
      based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment.
AB  - BACKGROUND: The prognostic significance of germline mutations in BRCA1 and BRCA2
      in women with breast cancer remains unclear. A combined analysis was performed to
      address this uncertainty. METHODS: Two retrospective cohorts of Ashkenazi Jewish
      women undergoing breast-conserving treatment for invasive cancer between 1980 and
      1995 (n = 584) were established. Archived tissue blocks were used as the source
      of DNA for Ashkenazi Jewish BRCA1/BRCA2 founder mutation analysis. Paraffin
      embedded tissue and follow-up information was available for 505 women. RESULTS:
      Genotyping was successful in 496 women, of whom 56 (11.3%) were found to carry a
      BRCA1/BRCA2 founder mutation. After a median follow-up period of 116 months,
      breast cancer specific survival was worse in women with BRCA1 mutations than in
      those without (62% at 10 years versus 86%; P < 0.0001), but not in women with the
      BRCA2 mutation (84% versus 86% at 10 years; P = 0.76). Germline BRCA1 mutations
      were an independent predictor of breast cancer mortality in multivariate analysis
      (hazard ratio 2.4, 95% confidence interval 1.2-4.8; P = 0.01). BRCA1 status
      predicted breast cancer mortality only among women who did not receive
      chemotherapy (hazard ratio 4.8, 95% confidence interval 2.0-11.7; P = 0.001). The
      risk for metachronous ipsilateral cancer was not greater in women with germline
      BRCA1/BRCA2 founder mutations than in those without mutations (P = 0.68).
      CONCLUSION: BRCA1 mutations, but not BRCA2 mutations, are associated with reduced
      survival in Ashkenazi women undergoing breast-conserving treatment for invasive
      breast cancer, but the poor prognosis associated with germline BRCA1 mutations is
      mitigated by adjuvant chemotherapy. The risk for metachronous ipsilateral disease
      does not appear to be increased for either BRCA1 or BRCA2 mutation carriers, at
      least up to 10 years of follow up.

PMID- 14680496
TI  - Expression of androgen receptor and prostate-specific antigen in male breast
      carcinoma.
AB  - BACKGROUND: The androgen-regulated proteins prostate-specific antigen (PSA) and
      prostate-specific acid phosphatase (PSAP) are present in high concentrations in
      normal prostate and prostatic cancer and are considered to be tissue-specific to
      prostate. These markers are commonly used to diagnose metastatic prostate
      carcinoma at various sites including the male breast. However, expression of
      these two proteins in tumors arising in tissues regulated by androgens such as
      male breast carcinoma has not been thoroughly evaluated. METHODS: In this study
      we analyzed the expression of PSA, PSAP and androgen receptor (AR) by
      immunohistochemistry in 26 cases of male breast carcinomas and correlated these
      with the expression of other prognostic markers. RESULTS: AR, PSA and PSAP
      expression was observed in 81%, 23% and 0% of carcinomas, respectively. Combined
      expression of AR and PSA was observed in only four tumors. CONCLUSION: Although
      the biological significance of PSA expression in male breast carcinomas is not
      clear, caution should be exercised when it is used as a diagnostic marker of
      metastatic prostate carcinoma.

PMID- 14680497
TI  - Coexistence of HER2 over-expression and p53 protein accumulation is a strong
      prognostic molecular marker in breast cancer.
AB  - INTRODUCTION: Many laboratories are currently evaluating the usefulness of
      determination of HER2, p53, and Ki67 proliferation indices using
      immunohistochemical techniques in cancer. Although the available studies suggest
      that these factors might indeed be helpful in making treatment decisions in
      cancer patients, their clinical usefulness is still controversial. METHODS:
      Expression of HER2, p53, and Ki67 was examined by immunohistochemistry in samples
      of breast tissue from 506 patients with invasive ductal carcinoma, obtained
      between 1981 and 1999 (median follow up period 82 months), and their significance
      for prognosis was analyzed. RESULTS: Of the 506 carcinoma tissue samples, 20.1%,
      29.0%, and 53.6% were positive for HER2 over-expression, p53 protein
      accumulation, and Ki67 expression, respectively. Over-expression of HER2
      significantly reduced disease free (P = 0.02) and overall survival (P = 0.005).
      Accumulation of p53 protein significantly decreased disease free (P = 0.01) and
      overall survival (P = 0.01). Patients with tumors that were positive for both
      HER2 and p53 relapsed and died within a significantly shorter period of time
      after surgery (P = 0.0001 and P < 0.0001, respectively). In multivariate
      analysis, patients with both HER2 and p53 positive tumors had considerably
      decreased overall survival (P = 0.04), as did patients with larger tumor size and
      positive lymph node status. CONCLUSION: The findings of the present study
      indicate that the coexistence of HER2 over-expression and p53 protein
      accumulation is a strong prognostic molecular marker in breast cancer.

PMID- 14680498
TI  - Prevention of mammary carcinogenesis by short-term estrogen and progestin
      treatments.
AB  - INTRODUCTION: Women who have undergone a full-term pregnancy before the age of 20
      have one-half the risk of developing breast cancer compared with women who have
      never gone through a full-term pregnancy. This protective effect is observed
      universally among women of all ethnic groups. Parity in rats and mice also
      protects them against chemically induced mammary carcinogenesis. METHODS: Seven
      week-old virgin Lewis rats were given N-methyl-N-nitrosourea. Two weeks later the
      rats were treated with natural or synthetic estrogens and progestins for 7-21
      days by subcutaneous implantation of silastic capsules. RESULTS: In our current
      experiment, we demonstrate that short-term sustained exposure to natural or
      synthetic estrogens along with progestins is effective in preventing mammary
      carcinogenesis in rats. Treatment with 30 mg estriol plus 30 mg progesterone for
      3 weeks significantly reduced the incidence of mammary cancer. Short-term
      exposure to ethynyl estradiol plus megesterol acetate or norethindrone was
      effective in decreasing the incidence of mammary cancers. Tamoxifen plus
      progesterone treatment for 3 weeks was able to confer only a transient protection
      from mammary carcinogenesis, while 2-methoxy estradiol plus progesterone was
      effective in conferring protection against mammary cancers. CONCLUSIONS: The data
      obtained in the present study demonstrate that, in nulliparous rats, long-term
      protection against mammary carcinogenesis can be achieved by short-term
      treatments with natural or synthetic estrogen and progesterone combinations.

PMID- 14680499
TI  - Basic fibroblast growth factor and vascular endothelial growth factor serum
      levels in breast cancer patients and healthy women: useful as diagnostic tools?
AB  - INTRODUCTION: The aim of the present study was to analyze the relationship
      between the expression of vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (bFGF) in breast cancer cells and the corresponding
      serum levels in individual patients. The study also evaluated the potential of
      serum levels of the two growth factors as diagnostic markers in a case-control
      study. METHODS: VEGF expression and bFGF expression were determined in 62 and 63
      tumor samples, respectively. Serum VEGF and bFGF levels were determined in 54 and
      65 healthy women and in 69 and 73 breast cancer patients, respectively, using a
      quantitative sandwich enzyme immunoassay technique. RESULTS: A direct correlation
      was observed between VEGF expression and bFGF expression in individual tumors (P
      = 0.001) and between serum levels (P = 0.038) in individual patients, but not
      between tumor cell expression and the corresponding serum level for either growth
      factor. Median values of serum levels in healthy women and breast cancer patients
      were not different for VEGF (P = 0.055), but were significantly different for
      bFGF (P < 0.001). The receiver operating characteristic curve identified a serum
      bFGF concentration of 1.0 pg/ml, with 84.9% sensitivity and 63.1% specificity, as
      the best cut-off value to discriminate between healthy women and breast cancer
      patients. An age-based subgroup analysis showed that serum values of patients
      older than 70 years of age mainly contributed to the high accuracy. CONCLUSIONS:
      Our data repropose bFGF as a noninvasive diagnostic tool for breast cancer.

PMID- 14680501
TI  - From antibody insult to fibrosis in neonatal lupus - the heart of the matter.
AB  - Few diseases exemplify the integration of research from bench to bedside as well
      as neonatal lupus, often referred to as a model of passively acquired
      autoimmunity. In essence, this disease encompasses two patients, both the mother
      and her child. The signature histologic lesion of autoimmune-associated
      congenital heart block is fibrosis of the conducting tissue, and in some cases
      the surrounding myocardium. It is astounding how rapid and, in most cases,
      irreversible is the fibrotic response to injury. The mechanism by which maternal
      anti-SSA/Ro-SSB/La antibodies initiate and perpetuate inflammation, and eventuate
      in scarring of the atrioventricular node, is not yet defined. In vitro and in
      vivo studies suggest that one pathologic cascade leading to scarring may be
      initiated via apoptosis, resulting in translocation of SSA/Ro-SSB/La antigens and
      subsequent surface binding by maternal autoantibodies. These opsonized
      cardiocytes are phagocytosed by macrophages, which secrete factors that
      transdifferentiate fibroblasts into myofibroblasts, a scarring phenotype.
      Dissecting the individual components in this fibrotic pathway should provide
      insights into the rarity of irreversible injury and should form the basis of
      rational approaches to prevention and treatment.

PMID- 14680502
TI  - Are synovial biopsies of diagnostic value?
AB  - Synovial tissue is readily accessible by closed needle or arthroscopic biopsy.
      These techniques provide adequate tissue for most diagnostic requirements.
      Examination of synovial tissue can assist in the diagnosis of some joint
      infections, and in several atypical or rare synovial disorders. Histological
      confirmation is not normally required for diagnosis of the common forms of
      inflammatory arthritis, including rheumatoid arthritis (RA). In patients with
      either established or early RA, immunohistological measures of inflammation in
      synovial tissue are associated with clinical measures of disease activity, may
      predict the clinical outcome, and change in response to treatment. Surrogate
      markers of disease activity and outcome that have been identified in synovial
      tissue include components of the cellular infiltrate, and several mediators of
      inflammation and matrix degradation. There is evidence that the very early
      introduction of disease-modifying therapy inhibits progressive structural damage
      maximally. Clinicians exploiting this 'window of opportunity' therefore require
      very early indicators of the diagnosis and outcome in patients who present with
      an undifferentiated inflammatory arthritis. Some immunohistological features have
      been described that distinguish patients who are likely to develop progressive RA
      and who might benefit most from early aggressive therapeutic intervention. In
      this regard, the inclusion of pharmacogenomic and proteomic techniques in the
      analysis of synovial tissue presents some exciting possibilities for future
      research.

PMID- 14680503
TI  - Microarray analysis of gene expression in lupus.
AB  - Recent advances in the study of global patterns of gene expression with the use
      of microarray technology, coupled with data analysis using sophisticated
      statistical algorithms, have provided new insights into pathogenic mechanisms of
      disease. Complementary and reproducible data from multiple laboratories have
      documented the feasibility of analysis of heterogeneous populations of peripheral
      blood mononuclear cells from patients with rheumatic diseases through use of this
      powerful technology. Although some patterns of gene expression, including
      increased expression of immune system cell surface activation molecules, confirm
      previous data obtained with other techniques, some novel genes that are
      differentially expressed have been identified. Most interesting is the dominant
      pattern of interferon-induced gene expression detected among blood mononuclear
      cells from patients with systemic lupus erythematosus and juvenile
      dermatomyositis. These data are consistent with longstanding observations
      indicating increased circulating interferon-alpha in the blood of patients with
      active lupus, but draw attention to the dominance of the interferon pathway in
      the hierarchy of gene expression pathways implicated in systemic autoimmunity.

PMID- 14680500
TI  - Neural immune pathways and their connection to inflammatory diseases.
AB  - Inflammation and inflammatory responses are modulated by a bidirectional
      communication between the neuroendocrine and immune system. Many lines of
      research have established the numerous routes by which the immune system and the
      central nervous system (CNS) communicate. The CNS signals the immune system
      through hormonal pathways, including the hypothalamic-pituitary-adrenal axis and
      the hormones of the neuroendocrine stress response, and through neuronal
      pathways, including the autonomic nervous system. The hypothalamic-pituitary
      gonadal axis and sex hormones also have an important immunoregulatory role. The
      immune system signals the CNS through immune mediators and cytokines that can
      cross the blood-brain barrier, or signal indirectly through the vagus nerve or
      second messengers. Neuroendocrine regulation of immune function is essential for
      survival during stress or infection and to modulate immune responses in
      inflammatory disease. This review discusses neuroimmune interactions and evidence
      for the role of such neural immune regulation of inflammation, rather than a
      discussion of the individual inflammatory mediators, in rheumatoid arthritis.

PMID- 14680504
TI  - Leukotrienes, mast cells, and T cells.

PMID- 14680505
TI  - Ageing, autoimmunity and arthritis: Perturbations of TCR signal transduction
      pathways with ageing - a biochemical paradigm for the ageing immune system.
AB  - It is widely accepted that cell-mediated immune functions decline with age,
      rendering an individual more susceptible to infection and possibly cancer, as
      well as to age-associated autoimmune diseases. The exact causes of T-cell
      functional decline are not known. One possible cause could be the development of
      defects in the transduction of mitogenic signals following TCR stimulation. This
      T-cell hyporesponsiveness due to defects of signalling through the TCR either
      from healthy elderly subjects or from individuals with autoimmune diseases such
      as rheumatoid arthritis or systemic lupus erythematosus results in an impaired
      ability to mount efficient immune responses and to maintain responsiveness to
      foreign antigens. This implies that a high proportion of autoreactive T cells
      might accumulate either intrathymically or in the periphery. T-cell anergy and
      differential TCR signalling could thus also be key players in the disruption of
      tolerance and the onset of autoimmune diseases. The increasing number of the
      elderly may lead to an increase of clinically important autoimmune diseases. We
      will review the signal transduction changes through the TCR-CD3 complex in T
      lymphocytes from healthy elderly subjects, which result in a modification of the
      activation of transcription factors involved in IL-2 gene expression leading to
      decreased IL-2 production. The putative contribution of altered T-cell signalling
      with ageing in the development of autoimmune diseases will be also discussed.

PMID- 14680506
TI  - Impact of VIP and cAMP on the regulation of TNF-alpha and IL-10 production:
      implications for rheumatoid arthritis.
AB  - Vasoactive intestinal peptide (VIP) is an anti-inflammatory immunomodulatory
      neuropeptide with therapeutic potential demonstrated for collagen-induced
      arthritis. The aim of this study was to characterise its potential anti-arthritic
      effect on human monocytes, macrophages, T cells, and rheumatoid arthritis
      synovial membrane cells. Monocytes, macrophages, and T cells derived from human
      peripheral blood were treated with VIP and compared with other cAMP-elevating
      drugs for a range of activating stimuli. Cytokine production was assessed for
      cell cultures and, in addition, the ability of VIPs to activate cAMP response
      element binding protein. VIP partially suppressed monocyte- and macrophage
      derived tumour necrosis factor alpha (TNF-alpha) with no effect on IL-10, whereas
      VIP fails to regulate IL-10 and TNF-alpha production by T lymphocytes. No such
      modulation of cytokine profile was observed for rheumatoid arthritis synovial
      membrane cells. Elevation of intracellular cAMP, on the other hand, potently
      suppressed macrophage TNF-alpha production and modulated T-cell response by
      inhibiting TNF-alpha and IFN-gamma. VIP's lack of effect on IL-10 and its slight
      effect on TNF-alpha results from cAMP being rapidly degraded as the
      phosphodiesterase IV inhibitor, rolipram, rescues cAMP-dependent activation of
      cAMP response element binding protein. Interestingly, macrophages stimulated with
      phorbol 12-myristate 13-acetate/ionomycin displayed an augmented IL-10 response
      upon addition of dibutyryl cAMP, with corresponding downregulation in TNF-alpha,
      suggesting a complex interaction between protein kinase C and protein kinase A in
      cytokine regulation. In conclusion, VIP may represent an efficaceous anti
      arthritic treatment modulating macrophage and T-cell cytokine profiles when used
      alongside a phosphodiesterase inhibitor.

PMID- 14680507
TI  - Electrophoretic characterization of species of fibronectin bearing sequences from
      the N-terminal heparin-binding domain in synovial fluid samples from patients
      with osteoarthritis and rheumatoid arthritis.
AB  - Fragments of fibronectin (FN) corresponding to the N-terminal heparin-binding
      domain have been observed to promote catabolic chondrocytic gene expression and
      chondrolysis. We therefore characterized FN species that include sequences from
      this domain in samples of arthritic synovial fluid using one-and two-dimensional
      (1D and 2D) Western blot analysis. We detected similar assortments of species,
      ranging from ~47 to greater than 200 kDa, in samples obtained from patients with
      osteoarthritis (n = 9) versus rheumatoid arthritis (n = 10). One of the
      predominant forms, with an apparent molecular weight of ~170 kDa, typically
      resolved in 2D electrophoresis into a cluster of subspecies. These exhibited
      reduced binding to gelatin in comparison with a more prevalent species of ~200+
      kDa and were also recognized by a monoclonal antibody to the central cell-binding
      domain (CBD). When considered together with our previous analyses of synovial
      fluid FN species containing the alternatively spliced EIIIA segment, these
      observations indicate that the ~170-kDa species includes sequences from four FN
      domains that have previously, in isolation, been observed to promote catabolic
      responses by chondrocytes in vitro: the N-terminal heparin-binding domain, the
      gelatin-binding domain, the central CBD, and the EIIIA segment. The ~170-kDa N
      terminal species of FN may therefore be both a participant in joint destructive
      processes and a biomarker with which to gauge activity of the arthritic process.

PMID- 14680508
TI  - HLA class II associations with rheumatic heart disease among clinically
      homogeneous patients in children in Latvia.
AB  - Genetic control of immune reactions has a major role in the development of
      rheumatic heart disease (RHD) and differs between patients with rheumatic fever
      (RF). Some authors think the risk of acquiring RHD is associated with the HLA
      class II DR and DQ loci, but other views exist, due to the various HLA-typing
      methods and ways of grouping cases. Our goal was to determine the relations
      between HLA class II alleles and risk of or protection from RF in patients with
      relatively homogeneous clinical manifestations. A total of 70 RF patients under
      the age of 18 years were surveyed in Latvia. HLA genotyping of DRB1*01 to DRB1*18
      and DQB1*0201-202, *0301-305, *0401-402, *0501-504, and *0601-608 was performed
      using polymerase chain reaction sequence-specific primers. Data for a control
      group of 100 healthy individuals typed for HLA by the same method were available
      from the databank of the Immunology Institute of Latvia. Of the RF patients, 47
      had RHD and 8 had Sydenham's chorea. We concluded that HLA class II DRB1*07
      DQB1*0401-2 and DRB1*07-DQB1*0302 could be the risk alleles and HLA class II
      DRB1*06 and DQB1*0602-8, the protective ones. Patients with mitral valve
      regurgitation more often had DRB1*07 and DQB1*0401-2, and patients with
      multivalvular lesions more often had DRB1*07 and DQB1*0302. In Sydenham's chorea
      patients, the DQB1*0401-2 allele was more frequent. Genotyping control showed a
      high risk of RF and RHD in patients with DRB1*01-DQB1*0301-DRB1*07-DQB1*0302 and
      DRB1*15-DQB1*0302-DRB1*07-DQB1*0303.

PMID- 14680509
TI  - Etanercept versus etanercept plus methotrexate: a registry-based study suggesting
      that the combination is clinically more efficacious.
AB  - Etanercept can be used both as monotherapy and in combination with methotrexate
      (MTX), but direct comparisons of these two options have not yet been reported. In
      order to compare the results seen in actual practice between these two options,
      clinical data on 97 patients followed in the Stockholm TNFalpha Follow-Up
      Registry were analysed. In 57 of these patients etanercept was added to
      previously started MTX while the others were treated with etanercept alone. The
      two groups had similar levels of disease activity at baseline. After 3 months, a
      significantly lower mean disease activity score (28-joint count-based disease
      activity score) was attained by the patients on etanercept plus MTX. In this
      group, the number of patients achieving European League Against Rheumatism
      defined remission was also significantly greater. Other disease outcomes showed
      non-significant trends in the same direction. These data suggest that the
      combination of etanercept plus MTX is clinically more efficacious than etanercept
      alone.

PMID- 14680510
TI  - Quantitative biomarker analysis of synovial gene expression by real-time PCR.
AB  - Synovial biomarker analysis in rheumatoid arthritis can be used to evaluate drug
      effect in clinical trials of novel therapeutic agents. Previous studies of
      synovial gene expression for these studies have mainly relied on histological
      methods including immunohistochemistry and in situ hybridization. To increase the
      reliability of mRNA measurements on small synovial tissue samples, we developed
      and validated real time quantitative PCR (Q-PCR) methods on biopsy specimens. RNA
      was isolated from synovial tissue and cDNA was prepared. Cell-based standards
      were prepared from mitogen-stimulated peripheral blood mononuclear cells. Real
      time PCR was performed using TaqMan chemistry to quantify gene expression
      relative to the cell-based standard. Application of the cellular standard curve
      method markedly reduced intra- and inter-assay variability and corrected
      amplification efficiency errors compared with the C(t) method. The inter-assay
      coefficient of variation was less than 25% over time. Q-PCR methods were
      validated by demonstrating increased expression of IL-1beta and IL-6 expression
      in rheumatoid arthritis synovial samples compared with osteoarthritis synovium.
      Based on determinations of sampling error and coefficient of variation, twofold
      differences in gene expression in serial biopsies can be detected by assaying
      approximately six synovial tissue biopsies from 8 to 10 patients. These data
      indicate that Q-PCR is a reliable method for determining relative gene expression
      in small synovial tissue specimens. The technique can potentially be used in
      serial biopsy studies to provide insights into mechanism of action and
      therapeutic effect of new anti-inflammatory agents.

PMID- 14680511
TI  - Differential gene expression in pristane-induced arthritis susceptible DA versus
      resistant E3 rats.
AB  - Arthritis susceptibility genes were sought by analysis of differential gene
      expression between pristane-induced arthritis (PIA)-susceptible DA rats and PIA
      resistant E3 rats. Inguinal lymph nodes of naive animals and animals 8 days after
      pristane injection were analyzed for differential gene expression. mRNA
      expression was investigated by microarray and real-time PCR, and protein
      expression was analyzed by flow cytometry or ELISA. Twelve genes were
      significantly differentially expressed when analyzed by at least two independent
      methods, and an additional five genes showed a strong a tendency toward
      differential expression. In naive DA rats IgE, the bone marrow stromal cell
      antigen 1 (Bst1) and the MHC class II beta-chain (MhcII) were expressed at a
      higher level, and the immunoglobulin kappa chain (Igkappa) was expressed at a
      lower level. In pristane-treated DA rats the MHC class II beta-chain, gelatinase
      B (Mmp9) and the protein tyrosine phosphatase CL100 (Ptpn16) were expressed at a
      higher level, whereas immunoglobulins, the CD28 molecule (Cd28), the mast cell
      specific protease 1 (Mcpt1), the carboxylesterase precursor (Ces2), K-cadherin
      (Cdh6), cyclin G1 (Ccng1), DNA polymerase IV (Primase) and the tumour associated
      glycoprotein E4 (Tage) were expressed at a lower level. Finally, the
      differentially expressed mRNA was confirmed with protein expression for some of
      the genes. In conclusion, the results show that animal models are well suited for
      reproducible microarray analysis of candidate genes for arthritis. All genes have
      functions that are potentially important for arthritis, and nine of the genes are
      located within genomic regions previously associated with autoimmune disease.

PMID- 14680512
TI  - Solvent effects in permeation assessed in vivo by skin surface biopsy.
AB  - BACKGROUND: Transdermal drug delivery has become an important means of drug
      administration. It presents numerous advantages but it is still limited by the
      small number of drugs with a suitable profile. The use of solvents that affect
      the skin barrier function is one of the classic strategies of penetration
      enhancement. Some of these solvents have well characterised actions on the
      stratum corneum, but the majority are still selected using empirical criteria.
      The objective of this work was to conduct a systematic study on the ability to
      affect skin permeation of solvents commonly used in transdermal formulations. An
      innovative methodology in this area was employed, consisting of the combination
      of skin surface biopsy with colorimetry. METHODS: The study compared in vivo
      differences in the permeation of a hydrophilic (methylene blue) and a lipophilic
      (Sudan III) dye, after treatment of the skin with different vehicles. Consecutive
      skin surface biopsies of each site were taken and the cumulative amounts of the
      dyes in the stripped stratum corneum were measured by reflectance colourimetry.
      RESULTS: Results indicate that the amount of methylene blue present in the
      stratum corneum varied significantly with different skin pre-treatments. Some
      solvents provided a 1.5 fold penetration enhancement but others decreased by
      almost half the permeation of the dye. The permeation of Sudan III was less
      significantly affected by solvent pre-treatment. CONCLUSIONS: This study has only
      superficially explored the potential of the combination of skin surface biopsy
      and colourimetry, but the encouraging results obtained confirm that the
      methodology can be extended to the study of more complex formulations.

PMID- 14680513
TI  - TGF-beta induces the expression of SAP30L, a novel nuclear protein.
AB  - BACKGROUND: We have previously set up an in vitro mesenchymal-epithelial cell co
      culture model which mimics the intestinal crypt villus axis biology in terms of
      epithelial cell differentiation. In this model the fibroblast-induced epithelial
      cell differentiation from secretory crypt cells to absorptive enterocytes is
      mediated via transforming growth factor-beta (TGF-beta), the major inhibitory
      regulator of epithelial cell proliferation known to induce differentiation in
      intestinal epithelial cells. The aim of this study was to identify novel genes
      whose products would play a role in this TGF-beta-induced differentiation.
      RESULTS: Differential display analysis resulted in the identification of a novel
      TGF-beta upregulated mRNA species, the Sin3-associated protein 30-like, SAP30L.
      The mRNA is expressed in several human tissues and codes for a nuclear protein of
      183 amino acids 70% identical with Sin3 associated protein 30 (SAP30). The
      predicted nuclear localization signal of SAP30L is sufficient for nuclear
      transport of the protein although mutating it does not completely remove SAP30L
      from the nuclei. In the nuclei SAP30L concentrates in small bodies which were
      shown by immunohistochemistry to colocalize with PML bodies only partially.
      CONCLUSIONS: By reason of its nuclear localization and close homology to SAP30 we
      believe that SAP30L might have a role in recruiting the Sin3-histone deacetylase
      complex to specific corepressor complexes in response to TGF-beta, leading to the
      silencing of proliferation-driving genes in the differentiating intestinal
      epithelial cells.

PMID- 14680514
TI  - The socio-economic impact of telehealth: a systematic review.
AB  - We reviewed the socio-economic impact of telehealth, focusing on nine main areas:
      paediatrics, geriatrics, First Nations (i.e. indigenous peoples), home care,
      mental health, radiology, renal dialysis, rural/remote health services and
      rehabilitation. A systematic search led to the identification of 4646 citations
      or abstracts; from these, 306 sources were analysed. A central finding was that
      telehealth studies to date have not used socio-economic indicators consistently.
      However, specific telehealth applications have been shown to offer significant
      socio-economic benefit, to patients and families, health-care providers and the
      health-care system. The main benefits identified were: increased access to health
      services, cost-effectiveness, enhanced educational opportunities, improved health
      outcomes, better quality of care, better quality of life and enhanced social
      support. Although the review found a number of areas of socio-economic benefit,
      there is the continuing problem of limited generalizability.

PMID- 14680515
TI  - Potential effect of patient-assisted teledermatology on outpatient referral
      rates.
AB  - We carried out a pilot study on the feasibility and accuracy of store-and-forward
      teledermatology based on patient-provided images and history as a triage tool for
      outpatient consultation. Patients referred by their general practitioner provided
      a history and images via the Internet. The information was reviewed by one of 12
      teledermatologists and the patient then visited a different dermatologist in
      person within two days. Three independent dermatologists compared the remote and
      in-person diagnoses in random order to determine diagnostic agreement. Broader
      agreement was also measured, by comparing the main disease groups into which the
      two diagnoses fell. The teledermatologists indicated whether an in-person
      consultation or further investigations were necessary. There were 105 eligible
      patients, aged four months to 72 years, who were willing to participate. For the
      96 cases included in the analysis, complete diagnostic agreement was found in 41%
      (n=39), partial diagnostic agreement in 10% (n=10) and no agreement in 49%
      (n=47). There was disease group agreement in 66% of cases (n=63). Nearly a
      quarter (23%) of participating patients could have safely been managed without an
      in-person visit to a dermatologist.

PMID- 14680516
TI  - Validation of vital signs recorded via a new telecare system.
AB  - A telecare system (Medic4All) has been developed that relies on a wireless
      wristwatch-like sensor to measure the pulse wave from the radial artery. From
      this, the heart rate and respiration rate are derived. The system's performance
      was examined by comparing the results obtained from the pulse wave signal with
      those obtained from conventional electrocardiographic and spirometer devices. A
      total of 144 patients participated in the study; their mean (SD) age was 43 (18)
      years. There were 44 cardiac patients in group 1 and 100 healthy patients, who
      were studied in their homes, in group 2. There was a significant correlation
      between the heart rates measured by the two monitoring methods. A 'difference
      versus average' analysis showed that the error distribution had a mean (SD) value
      of -0.1 (3.3) beats/min. Similarly, the respiration rates measured by the two
      techniques were significantly correlated. The error distribution had a mean (SD)
      value of 0.1 (1.9) respirations/min. The present study suggests that the wrist
      worn sensor represents a promising tool for online detection and monitoring of
      vital signs in the home.

PMID- 14680517
TI  - Effective delivery of neonatal stabilization education using videoconferencing in
      Manitoba.
AB  - We compared face-to-face and videoconference delivery of an education programme
      for health professionals on the subject of neonatal stabilization skills. A pre
      test/post-test control group design was used to compare knowledge acquisition and
      satisfaction between the two modalities. There were no statistically significant
      differences between delivery modalities for knowledge acquisition. Both groups
      showed significant gains in knowledge when pre- and post-test scores were
      compared. Responses to most of the items in a survey of satisfaction with the
      course did not differ significantly between the two groups. Face-to-face
      participants expressed higher levels of comfort in interacting with the
      presenter, and those in the videoconference group were more willing to receive
      the course via videoconference in the future. Videoconferencing provided an
      effective and acceptable way of delivering neonatal stabilization skills.

PMID- 14680518
TI  - Development of a teleconsultation system for communication between
      physiotherapists concerning children with complex movement and postural
      disorders.
AB  - We investigated whether a relatively low-cost, PC-based teleconsultation system
      could be used for interinstitutional communication about children with complex
      movement and postural disorders. Four paediatric physiotherapists in three
      different institutions participated. Both email and videoconferencing were
      tested. Videoconferencing was unsuccessful, as the low-bandwidth analogue lines,
      used by the majority of the therapists, made the quality of the realtime video
      images very poor. However, email with attached video-recordings was successful
      and the therapists used the system to consult each other about 20 cases. The
      therapists regarded the system as effective in clinical practice. However, some
      improvements would be desirable, such as making the system quicker to use and
      reducing the number of technical errors. Nonetheless, structured communication
      between physicians about complex postural and movement disorders appears to be
      promising both for patient referral and for decisions concerning treatment.

PMID- 14680519
TI  - The reality of applying an assessment guideline to a telemedicine mental health
      programme.
AB  - A guideline for assessment of telemedicine applications was used by the Alberta
      Mental Health Board (AMHB) in its evaluation of a telemedicine mental health
      (TMH) service. Many attributes referred to in the guideline were well covered in
      the AMHB evaluation. However, there were limitations on the assessment of
      outcomes and cost-effectiveness. From the perspective of the AMHB, the guideline
      was helpful, although more so in the earlier stages of the TMH service than for
      its appraisal as it reached maturity. The measures of performance suggested by
      the guideline did not fully match local operational conditions. Constraints on
      the assessment of the mature TMH service included the complexity of the network,
      the limited resources available for evaluation and the routine administrative
      demands of decision makers. This experience points to the usefulness of
      standardized assessment approaches to telemedicine, but also to their
      limitations.

PMID- 14680521
TI  - E-referral and e-triage as mechanisms for enhancing and monitoring patient care
      across the primary-secondary provider interface.

PMID- 14680523
TI  - The telemedicine curriculum.

PMID- 14680522
TI  - A virtual user involvement forum for people living with motor neuron disease.

PMID- 14680524
TI  - Telemedicine education.

PMID- 14680527
TI  - PCL-R psychopathy predicts disruptive behavior among male offenders in a Dutch
      forensic psychiatric hospital.
AB  - In this study, the relationship between psychopathy, according to the Dutch
      language version of Hare's Psychopathy Checklist-Revised (PCL-R), and various
      types of disruptive behavior during inpatient forensic psychiatric treatment is
      investigated. Ninety-two male participants were administered the PCL-R following
      admission to an inpatient forensic hospital. From daily hospital information
      bulletins, incidents of verbal abuse, verbal threat, physical violence, and
      violation of hospital rules were derived. Also, the number of seclusion episodes
      was recorded. As expected, significant correlations were found between PCL-R
      scores and verbal abuse, verbal threat, violation of rules, total number of
      incidents, and frequency of seclusion. Psychopaths (PCL-R > or = 30) were
      significantly more often involved in incidents than nonpsychopaths. Multiple
      regression analyses revealed that the PCL-R Factor 2 score in particular
      contributed uniquely to the prediction of the total number of incidents. The
      findings are discussed in terms of their clinical implications.

PMID- 14680526
TI  - The epidemiology of female rape victims who seek immediate medical care: temporal
      trends in the incidence of sexual assault and acquaintance rape.
AB  - Women who seek medical care following sexual assault are usually evaluated and
      treated in an emergency department (ED). Therefore, EDs can be an important
      source of sexual assault surveillance data. The authors compared the incidence of
      sexual assault presenting for emergency care in a single county during July to
      November of 1974 and 1991. Participants included all female sexual assault
      victims aged 14 and older who presented for ED evaluation. Treating physicians
      prospectively collected data using standardized forms. The z statistic was used
      to compare sexual assault incidence. There was a 60% increase in the incidence of
      sexual assault victims presenting for emergency care in 1991 compared to 1974,
      primarily due to an increase in the incidence of women presenting to the ED after
      rapes by known assailants. In contrast, the annual incidence of reported stranger
      assaults was similar in the two study years.

PMID- 14680528
TI  - Age and meanings of violence: women's experiences of partner violence in Finland.
AB  - The first survey carried out in Finland specifically to study men's violence
      against women showed that partner violence is quite common in Finland and it is
      directed especially toward young women. The statistical findings don't support
      the idea that violence has become more widespread in Finland. Life situation
      factors that are usually viewed as making women vulnerable to spousal violence,
      such as having children, cohabiting, low educational level, and financial
      dependency on the male partner, failed to explain partnership violence against
      women in Finland as such, too. The author's objective is to find out whether
      meanings of violence have changed and whether this could be one reason why young
      women report in a survey such cases of violence that other women would not. This
      could explain why violence in partnerships is so common among young women in
      Finland.

PMID- 14680529
TI  - Vicarious trauma: a comparison of clinicians who treat survivors of sexual abuse
      and sexual offenders.
AB  - This study compared vicarious trauma in a random sample of male and female
      clinicians who treat survivors (n=95) and those who treat offenders (n=252). A
      national survey was conducted with members of the Association for the Treatment
      of Sexual Abusers (ATSA) and the American Professional Society on the Abuse of
      Children (APSAC). These data were used to test the relative contribution of
      variables theorized to contribute to two vicarious trauma effects (avoidance and
      intrusions) using the Impact of Event Scale. The sample reported high levels of
      avoidance and intrusions. Variables associated with vicarious trauma differed
      based on client population served. Sequential regression analyses were used to
      examine theoretically derived variables. Implications for practice and further
      research are discussed.

PMID- 14680530
TI  - Sexual deviance among male college students: prior deviance as an explanation.
AB  - Much research on sexual deviance on university and college campuses is limited by
      its narrow focus on group affiliation and leads to much speculation and
      conjecture. This article suggests that an alternative explanation is more
      suitable for explaining such an important and complex problem on college
      campuses. It argues that prior deviance serves as a more robust predictor
      variable of sexual deviance. Logistic regression analyses indicate a direct
      relationship between prior deviance and sexual deviance. The results lend support
      to the argument that group affiliation is not a suitable explanation for such a
      complex societal problem-sexual deviance. Limitations of the study and directions
      for future research on sexual deviance are discussed.

PMID- 14680531
TI  - Interpersonal rejection sensitivity in childhood sexual abuse survivors: mediator
      of depressive symptoms and anger suppression.
AB  - This study investigated whether interpersonal rejection sensitivity serves a
      mediating role between childhood sexual abuse (CSA) and three long-term
      psychological correlates of CSA in adult female survivors: depressive symptoms,
      anger suppression, and attenuated emotional expression. Interpersonal rejection
      sensitivity has been shown to be a risk factor for the development of depression
      and is elevated in CSA survivors. Similarly, attenuated emotional expression,
      particularly anger, has been related to adjustment difficulties in CSA survivors.
      Participants in this study were 355 female undergraduates, 34 of whom reported a
      history of CSA. Results demonstrated that interpersonal rejection sensitivity
      mediates the relationship between CSA and later depressive symptoms.
      Interpersonal rejection sensitivity partially mediated the relationship between
      CSA and anger suppression; however, it did not mediate the relationship between
      CSA and attenuated emotional expression. These results are examined within the
      context of the current literature on adult CSA survivors and their implications
      are discussed.

PMID- 14680532
TI  - Differences in trauma symptoms and family functioning in intra-and extrafamilial
      sexually abused adolescents.
AB  - This study investigated to what extent abuse-related symptoms and family
      functioning are related to intra- or extrafamilial sexual abuse. One hundred
      adolescents (12 to 18 years old) were recruited shortly after disclosure of the
      abuse. Information from the participants was obtained through self-report
      questionnaires and a semistructured interview. Fifty-three percent of the
      adolescents reported clinically significant symptoms. Data did not support the
      idea that intrafamilial sexually abused adolescents report more symptoms than
      extrafamilial sexually abused adolescents. Type of abuse did not account for the
      differences and variety of reported symptoms or for differences in family
      functioning. Family functioning-in particular, lack of cohesion- was an
      independent contributor to internalizing trauma-related problems.

PMID- 14680534
TI  - How will practices cope with information for the new GMS contract? Coronary heart
      disease data recording in five Scottish practices.
AB  - OBJECTIVES: To investigate whether practices will be ready for the data reporting
      requirements for the new General Medical Services (GMS) contract, using coronary
      heart disease (CHD) as an example. DESIGN: Cross-sectional survey. DATA SOURCES:
      Electronic general practitioner (GP) records of all CHD patients in five Scottish
      practices, validated by manual searches in 50 randomly selected patients in each
      practice. MAIN OUTCOME MEASURES: Recording of family history, smoking status,
      blood pressure (BP), diabetes testing, aspirin therapy and cholesterol
      measurement. RESULTS: It is extremely easy for practices with completely
      electronic patient records to extract a disease register (mean 10 min, range 38
      sec to 3 hr 6 min). Extraction of a complete dataset takes several days if it
      involves checking through paper records, whereas setting up and running a search
      from electronic records is possible in less than two hours. If practices use the
      same clinical system and identical data entry templates, the data can be directly
      compared. Some items that are easily recorded as part of routine clinical
      practice, such as prescribing of aspirin, are well recorded, but others, such as
      BP recording, are more of a problem. One hundred percent of the CHD patients
      sampled had a BP recording within the previous year, but some practices had these
      data in the paper records where they were not readily accessible. CONCLUSIONS: We
      have shown that in Scotland there is a high level of testing and recording of all
      the important information regarding patients with recorded CHD, irrespective of
      whether practices have fully electronic records, paper-based records, or a
      mixture of the two. If practices have fully electronic patient records, the
      information can be extracted easily, but unless there is a standard template, the
      information can only be viewed in isolation and is of little value for
      comparative purposes.

PMID- 14680535
TI  - How could primary care meet the informatics needs of UK Biobank? A Scottish
      proposal.
AB  - UK Biobank is an ambitious post-genomic project involving the recruitment and
      follow-up of 500 000 volunteers aged 45 to 69 years. Many primary care teams will
      be involved in the study directly or indirectly. The programme of research will
      use at least five data sources: paper-based questionnaires, blood samples,
      genotype information derived from the bloods, clinical/prescribing data from the
      medical records, and data on deaths. We describe three of the key challenges to
      primary care informatics posed by this project: patient recruitment,
      confidentiality, and data management. We then describe solutions proposed in
      Scotland, based on existing technologies. Some of these may be applicable
      elsewhere in the other Regional Collaborating Centres and other large-scale
      collaborative projects which rely on primary care informatics.

PMID- 14680536
TI  - Generating information from electronic patient records in general practice: a
      description of clinical care and gender inequalities in coronary heart disease
      using data from over two million patient records.
AB  - OBJECTIVES: To describe the epidemiology of coronary heart disease (CHD) in
      England and the activity of primary healthcare teams in managing patients with
      CHD, and also to demonstrate the utility of computerised patient records in
      providing access to epidemiological data and data reflecting healthcare activity.
      DESIGN: A descriptive survey of CHD and related clinical data, recorded using
      computerised clinical records, entered by primary healthcare teams. Aspects
      reported include prevalence of CHD, together with additional data reflecting
      clinical monitoring activity, therapeutic interventions and comorbidity in
      patients affected by CHD. SETTING: 317 general practices in 23 English primary
      care trusts (PCTs). DATA ACQUISITION: MIQUEST was used to interrogate 2 252 274
      computerised patient records. Data were extracted in the form of sex and age
      aggregated counts of patients meeting a range of extraction criteria. RESULTS:
      The observed crude prevalence of CHD is 40.3 per 1000 (males 46.6, females 34.2).
      A variety of findings are presented relating to the treatment, monitoring and
      comorbidities of CHD. Significant and systematic gender inequalities are
      demonstrated to exist in the monitoring and treatment of CHD. CONCLUSIONS:
      Extraction of data from computerised patient records is a valuable and
      practicable method of generating information to inform clinicians and National
      Health Service (NHS) organisations. Systematic gender disparities exist in the
      care delivered to patients with CHD.

PMID- 14680537
TI  - A methodology for the functional comparison of coding schemes in primary care.
AB  - There has been massive investment in the development of clinical terminologies
      for use in electronic patient records. However, there has been little published
      evidence for the added value for primary care that implementation of such a
      terminology would offer. This paper outlines a methodology that has been used to
      compare two existing coding schemes (Read codes 5 byte set and Clinical Terms
      Version 3-CTV3) and demonstrates their relative performance using a certainty
      agreement diagram. In the study described, CTV3 offers improved accuracy and
      consistency with improved usability. The potential advantages of the recently
      released terminology, SNOMED Clinical Terms, are briefly considered in this
      context.

PMID- 14680538
TI  - Using three-channel video to evaluate the impact of the use of the computer on
      the patient-centredness of the general practice consultation.
AB  - The aim of this study was to assess the feasibility of using three-channel video
      to explore the impact of the computer on general practitioner (GP) consultations.
      A previous study had highlighted the limitations of using single-channel video:
      firstly, there was a lack of information about exactly how the computer was being
      used, and secondly difficulty in interpreting the body language of the consulting
      clinician. More information was needed to understand the impact of the computer
      on the consultation, and in this pilot three-channel video was used to overcome
      these constraints. Four doctors consulted, with the patient's role played by an
      actor with a preset script and preloaded personal and family history record
      programmed into the computer. The output was analysed using the Roter Interaction
      Analysis System (RIAS) and observational methods were used to explore the effect
      of computers on aspects of verbal and non-verbal behaviour and the completeness
      of the computer data record. Three-channel video proved to be a feasible and
      valuable technique for the analysis of primary care GP consultations, with
      advantages over single-channel video. Interesting differences in non-verbal and
      verbal behaviour became apparent with different types of computer use during the
      consultation. Implications for the three-channel video technique for training,
      monitoring GP competence and providing feedback are discussed.

PMID- 14680539
TI  - Moving to paperlessness: a case study from a large general practice.
AB  - This case study reports the reasons why this large, multi-site general practice
      decided to move towards paperless practice in late 2001, and describes the
      progress and lessons learned to date. The principal operational reasons for this
      decision were problems associated with moving paper medical records between
      surgeries, and the realisation that resources to improve the computerised medical
      record could only come from redeploying the time spent handling paper records. A
      comprehensive plan was put in place to shift toward paperlessness. Motivating and
      changing working practices for clinical and support staff was as a great a
      challenge as upgrading the technology. The practice upgraded its computer system,
      and has installed scanning and automated generation of referral and other
      letters. The support staff skills have evolved from moving records to scanning
      documents and coding data. All clinical staff now consult on their computer, and
      code diagnoses and key clinical data. A networked digital dictation system allows
      typing to be centralised at one location, with the networking allowing printing
      at any site. Audit and quality improvement activities have increased, as the
      output from computer searches increasingly represents the quality of care
      provided. The implications of this case study are that a committed general
      practice can achieve a largely paperless environment in approximately two years.
      The practice is now fit to be part of any move towards integration of records
      within its local health community, and can demonstrate from its computer records
      that it meets the quality targets for primary care.

PMID- 14680540
TI  - "More Radical Steps" (2003) initiatives.

PMID- 14680541
TI  - Introduction to the Primary Care Informatics Working Group of the European
      Federation for Medical Informatics (EFMI).

PMID- 14680542
TI  - UK Primary Care Database Research Group.

PMID- 14680544
TI  - Minimizing risk in anonymous egg donation.
AB  - Assisted conception carries with it known and putative medical and surgical
      risks. Exposing healthy women to these risks in order to harvest eggs for
      donation when a safer alternative exists is morally and ethically unacceptable.
      Egg sharing minimizes risk and provides a source of eggs for donation. Anonymity
      protects all parties involved and should not be removed.

PMID- 14680545
TI  - Towards single births after assisted reproduction treatment.
AB  - The cause of increases in recorded multiple births is undoubtedly assisted human
      conception. Many arise when three or more embryos are replaced after IVF or ISCI.
      Others are due to multi-ovulation during artificial insemination or intrauterine
      inseminations, since complete control over numbers of ovulated eggs following
      ovarian stimulation is not fully possible. The frequency of multiple IVF births
      is best controlled by reducing numbers of transferred embryos to one or two.
      Methods to induce ovarian stimulation in amenorrhoeic and then in cyclic women 30
      years ago have been greatly refined and extended in current practice. Curiously,
      a great many of them produce oocytes which fail to implant after fertilization,
      whether natural or induced cycles are being used. This massive failure of most
      embryos to implant poses numerous questions on the evolution of this situation in
      humans.

PMID- 14680546
TI  - Clomiphene citrate versus letrozole for ovarian stimulation: a pilot study.
AB  - The purpose of this pilot study was to compare the endocrinological environment
      of cycles stimulated with clomiphene citrate (CC) or letrozole. Fifteen patients
      undergoing intrauterine insemination (IUI) received from day 3 to day 7 of the
      cycle either letrozole 2.5 mg/day (n = 7) or clomiphene citrate 100 mg/day (n =
      8). IUI was performed one day after the detection of LH peak. No luteal support
      was administered. Significantly lower serum oestradiol concentrations were
      present in the follicular phase on days 9, 13 and 15 of the cycle and in the
      luteal phase on days 3 and 6 post-IUI in the letrozole group compared with those
      in the CC group. Progesterone concentrations and oestradiol concentrations were
      significantly lower in the letrozole group than in the CC group on the day of LH
      peak. Significantly more follicles developed in patients in the CC group compared
      with those in the letrozole group. In conclusion, significantly lower oestradiol
      concentrations and fewer follicles are observed in cycles stimulated with 2.5 mg
      letrozole compared with cycles stimulated with 100 mg CC from day 3 to day 7 of
      the cycle.

PMID- 14680547
TI  - Compositional analyses of a human menopausal gonadotrophin preparation extracted
      from urine (menotropin). Identification of some of its major impurities.
AB  - Recently, a highly purified human menopausal gonadotrophin preparation (HMG) was
      launched. The composition and purity of this HMG (Menopur); Ferring
      Pharmaceuticals) with a claimed 1:1 ratio of FSH and LH was determined. Three
      gonadotrophins were observed: FSH, LH and human chorionic gonadotrophin (HCG).
      The immunoactivity for HCG was three-fold higher than the immunoactivity for LH.
      Because of the longer half-life of HCG as compared with LH, about 95% of the in
      vivo LH-receptor-mediated bioactivity is attributable to the presence of HCG.
      This is substantiated by biochemical analyses. To the best of the authors'
      knowledge, this relatively high amount of HCG can only be explained by assuming
      the addition of HCG from external sources, which is a well established practice
      for standardization purposes. In addition to gonadotrophins, a number of other
      proteins were detected. The amount of these impurities, as determined by reversed
      phase high-performance liquid chromatography on a peak-area basis, is at least
      30%. Therefore, it is concluded that this HMG preparation contains at most 70%
      gonadotrophins. Via a proteomics approach three major impurities were identified:
      leukocyte elastase inhibitor, protein C inhibitor, and zinc-alpha(2)
      glycoprotein. On the basis of the results obtained in this study, a comparison is
      made with recombinant FSH.

PMID- 14680548
TI  - Birth of a healthy female after preimplantation genetic diagnosis for Charcot
      Marie-Tooth type X.
AB  - The X-linked dominant form of Charcot-Marie-Tooth syndrome (CMTX) is a clinically
      and genetically heterogeneous hereditary disorder of the peripheral nerves caused
      by mutations in the GJB1 gene that encodes a gap junction protein named connexin
      32 (Cx32). Clinically, CMTX is characterized by peripheral motor and sensory
      deficit with muscle atrophy. A couple with a previous history of pregnancy
      termination after being diagnosed positive for CMTX by chorionic villus sampling,
      was referred for preimplantation genetic diagnosis (PGD). The female partner
      carried the causative H94Q, characterized by a C-->G substitution in codon 94 of
      exon 2 of the GJB1 gene. Embryos obtained after intracytoplasmic sperm injection
      (ICSI) were evaluated for the presence of the mother's mutation using polymerase
      chain reaction (PCR), followed by mutation analysis performed using the
      minisequencing method. Amelogenin sequences on the X and Y chromosomes were also
      co-amplified to provide a correlation between embryo gender and mutation
      presence. A single PGD cycle was performed, involving nine fertilized oocytes,
      five of which developed into good quality embryos useful for biopsy. Two
      unaffected embryos were transferred, resulting in a singleton pregnancy followed
      by the birth of a healthy female.

PMID- 14680550
TI  - Embryo development characteristics in Robertsonian and reciprocal translocations:
      a comparison of results with non-translocation cases.
AB  - The effect of translocations on embryo development was evaluated and results were
      compared in terms of embryo development with those of embryos obtained from
      standard intracytoplasmic sperm injection (ICSI) cycles. In 23 translocation
      carriers with 34 cycles, fertilization, pronuclear morphology scoring (PMS),
      developmental arrest, cleavage and blastocyst formation were evaluated and
      compared with embryos obtained from non-translocation cases undergoing ICSI (n =
      98 cycles). In 28 cycles, preimplantation genetic diagnosis (PGD) was performed
      on prezygotes (first and second polar body biopsy for female carriers; n = 3) or
      on embryos having seven or more blastomeres (blastomere biopsy; n = 25). In six
      cycles for four couples, probes for translocated chromosomes were not available,
      so PGD could not be performed. Overall, in translocation cases, a lower
      fertilization rate, a higher rate of retarded embryo development, and a lower
      rate of blastocyst formation were observed compared with embryos of non
      translocation cases. Fluorescence in-situ hybridization (FISH) analysis showed a
      70.9% abnormality rate for reciprocal translocations and 55.0% for Robertsonian
      translocations respectively. In cases with Robertsonian and reciprocal
      translocation carriers, the probability of poor embryo development, which may be
      a result of high segregation abnormalities, may negatively affect the outcome of
      assisted reproductive techniques. This poor prognosis should also be considered
      when genetic counselling for translocation is given.

PMID- 14680552
TI  - Preliminary experience of ovarian tissue cryopreservation procedure:
      alternatives, perspectives and feasibility.
AB  - Chemotherapy and radiotherapy induce premature ovarian failure in many patients
      treated for oncological or benign diseases. The present paper reviews the risk of
      developing premature ovarian failure according to the type of treatment and the
      different options to preserve fertility, focusing on the cryopreservation of
      ovarian tissue. This technique constitutes a promising approach to preserve the
      fertility of young patients and offers the advantage of storing a large number of
      follicles that could be subsequently transplanted or cultured in vitro to obtain
      mature oocytes. Based on 34 requests, from which 19 were performed, the
      feasibility of the ovarian cryopreservation procedure is evaluated. The medical
      and ethical approaches of this protocol are also discussed. Cryopreservation of
      ovarian tissue constitutes new hope for many patients, but must still be kept for
      selected cases, with a significant risk of premature ovarian failure after
      treatments such as bone marrow transplantation.

PMID- 14680553
TI  - On a fallacious invocation of the Barker hypothesis of anomalies in newborn rats
      due to mothers' food restriction in preimplantation phases.
AB  - A statistical re-evaluation indicates serious flaws in the paper by Kwong et al.,
      reporting that low birthweight and impaired development, and perhaps anomalous
      preimplantation embryo growth, were associated with food restriction during the
      preimplantation period. This paper has been used to confirm that early forms of
      protein deprivation in the preimplantation phase carry risks to IVF children.
      Errors in interpreting the nature of their study and a failure to apply the
      correct principles of statistical analysis in their hierarchical data structure
      have led to their flawed investigation. It is therefore proposed that such
      serious flaws cast doubt on their conclusions. The findings reported in this
      study should be withdrawn, and a rigorous statistical evaluation should be
      carried out to provide a proper assessment of the data.

PMID- 14680554
TI  - Embryo transfer: hysteroscopic assessment of transfer catheter effects on the
      endometrium.
AB  - So far as is known, this is the first series to report the effects of embryo
      transfers on endometrial integrity as assessed by direct hysteroscopic
      visualization. Subjects (n = 30) were patients of reproductive age undergoing
      diagnostic hysteroscopy. A mock embryo transfer was performed by a single
      clinician, immediately followed by saline hysteroscopy using a 2.7 mm
      hysteroscope. Hegar dilators or uterine sounds were not used. Representative
      video clips were recorded for independent assessment of endometrial integrity.
      (The movie sequence may be purchased for viewing on the internet at
      www.rbmonline.com/Article/1040; it is free to web subscribers.) Outcomes measured
      were ease of transfer (easy, moderate, difficult, very difficult) and details of
      the transfer technique. Endometrial damage was independently assessed and graded
      as follows: none, minor, moderate or severe. Of the easy transfers, 54% showed no
      endometrial damage. However, there 37% showed moderate to severe damage in the
      easy transfer group. Of the moderately difficult transfers, there was no clear
      association between perceived difficulty of transfer and amount of endometrial
      damage. Clinical perception of ease of transfer does not correlate well with the
      degree of endometrial disruption (P = 0.41). Use of hysteroscopy offers a unique
      insight into the effects of embryo transfer on endometrial integrity.

PMID- 14680555
TI  - Outcome of blastocyst transfer according to availability of excess blastocysts
      suitable for cryopreservation.
AB  - The purpose of this study was to assess the outcome of blastocyst transfer in
      relation to the presence or absence of excess blastocysts available for
      cryopreservation. The study was designed as a retrospective case series in a
      tertiary care private hospital. The study group consisted of 450 blastocyst stage
      embryo transfer cycles. In 139 cycles there were excess freezeable blastocysts
      (group 1), in 78 cycles there were excess but unfreezeable blastocysts (group 2),
      and in 233 cycles there were no excess blastocysts (group 3). A mean of three
      blastocysts was replaced in all groups. Treatment cycle characteristics,
      implantation and pregnancy rates following fresh and cryopreserved blastocyst
      transfer were assessed in each group. More embryos reached the blastocyst stage
      in group 1 and more blastocysts were of good quality. In group 1, clinical
      pregnancy and implantation rates (71 and 41%) were significantly higher compared
      with groups 2 (56 and 27%) and 3 (43 and 19%). Embryos that were selected for
      transfer among a cohort of good quality blastocysts yielded the highest
      implantation and pregnancy rates. Given a clinical pregnancy rate of 71%, an
      implantation rate per embryo of 41%, and a multiple pregnancy rate of 58%,
      serious consideration should be given to a single blastocyst transfer in these
      patients.

PMID- 14680556
TI  - Frozen embryos discarded in court decision.

PMID- 14680557
TI  - Is Germany reconsidering therapeutic cloning?

PMID- 14680558
TI  - [Expression of human osteoprotegerin gene in E. Coli and bioactivity analysis of
      expression product].
AB  - OBJECTIVE: To express human osteoprotegerin (OPG) in E. Coli and analyze its
      bioactivity in vitro. METHODS: Synthetic oligonucleotides were used to amplify
      human OPG gene by RT-PCR from total RNA of human osteosarcoma cell line MG63. The
      OPG cDNA coding for 380 amino acid residues was inserted into prokaryotic
      expression vector pRSET-A, transformed into competent E. Coli BL21, and induced
      by 0.1 mmol/l IPTG. SDS-PAGE and Western blot were performed to identify OPG-6His
      fusion protein. After purified by affinity chromatography, 1,000 microg/L or
      1,500 microg/L of OPG-6His were added into the mouse bone marrow cells culture
      medium. The number of tartrate-resistant acid phophatase (TRAP)-positive
      multinucleated cells and resorption pits were counted to assess the bioactivity
      of expression products. RESULTS: The sequence of OPG mature peptide encoding cDNA
      obtained in this experiment was as same as reported. SDS-PAGE showed 24% of total
      bacterial protein was of OPG-6His fusion protein. Western blot assay demonstrated
      that the molecular weight of recombinant protein was about 46 KD and could react
      specifically with human anti-OPG antibody. The mouse bone marrow cells were
      induced by 1alpha, 25-dihydroxyvitaminD3 (10(-8) mol/L) and Dexamethasone (10(-7)
      mol/L) to form osteoclastic-like multinucleated cells. 1,500 microg/L of purified
      OPG-6His protein could decrease the number of resorption pits and TRAP-positive
      multinucleated cells in vitro (P < 0.05), but it didn't show the same effects
      when the concentration of OPG-6His fusion protein was of 1,000 microg/L.
      CONCLUSIONS: Human OPG-6His fusion protein is expressed and purified in E. Coli.
      The expression products have moderate inhibitory effects on osteoclast
      differentiation and bone resorption in vitro only when excessive amount of
      proteins are added into the culture medium, indicating that prokaryotic
      expression of fuctionalal OPG protein awaits further investigation.

PMID- 14680559
TI  - [The influence of FasL gene expression upon hepatic metastasis of colorectal
      carcinoma].
AB  - OBJECTIVE: To study FasL gene expression in colorectal carcinoma and its
      influences on biological behaviour of colorectal cancer and hepatic metastasis.
      METHODS: FasL gene expressions were examined with RT-PCR technique in the primary
      locus of colorectal cancer, mucosa adjacent to cancer, and hepatic metastasis. HR
      8348 cells of human rectal cancer cell line were transfected with FasL cDNA. Cell
      growth suppression rates and cell response to 5-FU and carboplatin were observed
      and analysed with MTT method. RESULTS: FasL gene expressions were detected in the
      primary site of colorectal cancer (n = 58), cancer adjacent mucosa (n = 58), and
      hepatic metastasis (n = 28). The positive rate of FasL expression was 24%
      (14/58), 14% (8/58), 100% (28/28), respectively, in primary site, tumor adjacent
      mucoca and hepatic metastasis. FasL expression rate in hepatic metastasis was
      higher than that in the primary site (chi2 = 43.49, P < 0.01) and tumor adjacent
      mucosa (chi2 = 57.66, P < 0.01). In a group of patients with hepatic metastasis,
      FasL expression rate in primary site was higher than that in patients without
      hepatic metastasis (chi2 = 3.96, P < 0.05). In vitro experiment, positive
      expression of FasL was found in transfected HR-8348 cells. When 5-FU or
      carboplatin was added, there was a significant difference in growth suppression
      rate between FasL positive and control cancer cells (t = 9.02, t = 11.93, P <
      0.01). Under same concentration of chemotheraputic agent, survival rate of FasL
      positive HR-8348 cells was higher than that of control cells. CONCLUSIONS: FasL
      positive cancer cells have more powerful resistance to chemotheraputic drugs.
      Expression of FasL gene in colorectal cancer cells is related with immune evasion
      to escape killing by immune cells, showing stronger drug-resistance, and it
      facilitates hepatic metastasis.

PMID- 14680560
TI  - [Humeral head replacement for the complex treatment of proximal humerus
      fractures].
AB  - OBJECTIVE: To investigate indication, technical key during surgery and early
      results of humeral head replacement for the treatment of complicated proximal
      humerus fractures. METHODS: Sixteen patients who received humeral head
      replacement were reviewed with a mean follow-up period of 6.8 months. Of the 16
      patients, 15 suffered acute fractures with the mean interval between injury and
      surgery being 8 days. 1 case was a malunion after ORIF 1 year ago. The mean age
      for these patients were 58.9 years. Trauma series X-rays were taken at post
      operation 2-week, 6-week, 10-week, 16-week 6-month and the latest follow-up. SST
      (Simple Shoulder Test) questionnaire, ASES (American Shoulder & Elbow Surgeon)
      score, Constant-Murley score and UCLA score had been adopted for evaluation at
      the latest follow-up. RESULTS: The mean ASES score was 89.1 (64 - 94); the mean
      VAS score was 2.7 (0 - 5); the mean forward flexion was 128.1 degrees (90 degrees
      - 150 degrees ), external rotation 35 degrees (30 degrees - 40 degrees ),
      internal rotation at T8-T9 level (L1-T6); the mean Constant-Murley score was 85.7
      (53 - 95); the mean UCLA score was 30.4 (21 - 33); the mean number of questions
      for "yes" in SST questionnaire was 9.3 (7 - 11). The total satisfaction rate for
      pain relief was 93.8% (15/16), and functional recovery was 87.5% (14/16).
      CONCLUSIONS: Through strict indication control, appropriate timing, meticulous
      surgical techniques and long intense rehabilitation, satisfactory results can be
      obtained in humeral head replacement for the treatment of complicated proximal
      humerus fractures. Our report is only a preliminary one on early results, and a
      long-term follow-up data is needed for further evaluation.

PMID- 14680561
TI  - [Diagnosis and surgical treatment of middle lobe disease of lung: report of 163
      cases].
AB  - OBJECTIVE: To discuss the principle of diagnosis and surgical treatment of middle
      lobe diseases of right lung. METHODS: We analysed the clinical data and prognosis
      of 163 patients who suffered from middle lobe diseases of right lung and received
      surgical treatment. RESULTS: There were 97 men and 66 women in the group with the
      ratio 1.5:1, whose age arranged from 13 to 74 years. The shortest course was one
      week, and the longest 25 years. The average course was 30.3 months. 78 of 163
      patients with tumors were malignant (47.9%) and 85 benign (52.1%). The number of
      the patients below 50 years old was 91 and 81.3% of them were benign, which was
      very markedly higher than that of the patients with malignant tumors (P < 0.01).
      The number of the patients above 50 years old was 72 and 84.7% were malignant,
      which was very markedly higher than that of the patients with benign tumors (P <
      0.01); 8 of 11 patients (72.7%, 8/11) who suffered from tuberculosis combined
      with bronchoactesis. One of this group died from respiratory failure after
      operation, packed accumulation of fluid between lobes happened in seven cases
      (4.3%). The survival rate of 1, 3, 5 years of malignant patients at stages I, II
      were 88.4%, 62.8%, 51.2%, for that at stages III, IV were 76.5%, 41.2%, 14.7%.
      All of the four patients who received vage-resection, their malignant tumors
      recurred in one year after operation. No benign lesion recurred in 10 years.
      CONCLUSION: (1) It should be noticed that nearly half of middle lobe disease were
      malignant, especially to those whose ages were above 50 years old. (2) When the
      diagnosis is hard to be confirmed, open-thoracic exploration should be performed
      in order not to delay the treatment or enlarge the range of lung resection. (3)
      Most of middle lobe tuberculosis may be combined with bronchoactesis. (4) Setting
      drainage tube may be useful to decrease the risk of interlobe accumulation of
      fluid. (5) Vage resection is not suitable for carcinoma of middle lobe of lung.

PMID- 14680562
TI  - [Safeguard and management of the heart vales in congenital heart disease
      procedure].
AB  - OBJECTIVE: To summarize the experience in performing reoperation of valve
      dysfunction after congenital heart disease procedure. METHODS: From 1994 to 2001
      we reviewed the data of 13 patients with valve dysfunction after congenital heart
      disease operation, in which 8 patients after ventricular septal defect, 3 after
      atrioventricular canal and 2 after respectively tetralogy of Fallot and atrial
      septal defect were corrected. Before the first operation, 6 patients had
      presented the mild to moderate mitral regurgitation, 1 had aortic regurgitation.
      Other 6 patients had valves dysfunction occurring after the first operation,
      among them, 2 suffered from respectively residual shunt of the ventricular septal
      defect, 2 had anterior chordae rupture of tricuspid valve, one had an operative
      injured aortic valve and one had surviving of right ventricular outlet
      obstruction. Thirteen patients were reoperated, including mitral valve
      replacement in 6, tricuspid valve replacement in 2, aortic valve replacement in
      one, aortic valve replacement consists with mitral valve repair and tricuspid
      valve repair in one and tricuspid valve repair in 3. Concomitant procedures were
      performed. RESULTS: Low cardiac output occurred in 3 cases and there were 2 early
      deaths, due to cerebral air-embolism, respiratory and circulatory failure
      respectively. Other 11 cases discharged and were followed up well. CONCLUSIONS:
      It is important to safeguard and repair the valvular construction and function
      during the operation in congenital heart disease. Reoperation should be performed
      timely for obtaining recurrent and a good results.

PMID- 14680563
TI  - [Video-assisted thoracoscopic left sympathectomy for the treatment of congenital
      long QT syndrome].
AB  - OBJECTIVE: To assess the feasibility, safety and effectiveness of video-assisted
      thoracoscopic sympathectomy (VATS) for the treatment of congenital long QT
      syndrome. METHODS: Under general anaesthesia, pleural cavity was entered via two
      or three small incisions in the left intercostal space. The left thoracic
      sympathetic chain was identified and resected from T2 approximately T5. The lower
      one at the third of the left stellate ganglion was also resected. RESULTS: VATS
      resulted in a significant shortening in corrected QT intervals in three patients.
      The average QT interval of the four patients was 537.5 ms before VATS and 512.5
      ms after VATS. The heart rate of the patients remained unchanged. There were no
      major peri-operative complications apart from mild ptosis of the left upper
      eyelid in one patient who recovered in the following days. The syndrome recurred
      in one patient in syncopal events in four months after VATS. CONCLUSION: VATS is
      a safe as well as an effective technique for the treatment of congenital long QT
      syndromes.

PMID- 14680564
TI  - [Role of diffusion tensor imaging in neuronavigation surgery of brain tumors
      involving pyramidal tracts].
AB  - OBJECTIVE: To explore the role of diffusion tensor imaging (DTI) in
      neuronavigation surgery of brain tumors involving pyramidal tracts. METHODS:
      Forty-nine patients with brain tumors involving pyramidal tracts were randomly
      divided into trial group (DTI navigation) and control group (traditional
      navigation). The patients in trial group underwent DTI and T1 weighted 3D
      navigational magnetic resonance imaging (MRI) studies. The main white matter
      tracts were constructed by the DTI datasets, and merged to the anatomical
      structure, which was delineated by the T1-weighted three-dimensional fast spoiled
      gradient recalled sequence (3D/FSPGR). The relationship between the tumors and
      adjacent pyramidal tracts were segmented and reconstructed for three-dimensional
      visualization. RESULTS: In 25 patients of trial group and 24 patients of control
      group, the statistic analysis confirmed well balance of main variations. The
      tumors were completely resected in 12 patients (50.0%) of control group and in 20
      patients (80.0%) of trial group (P < 0.05). Postoperative aggravated
      contralateral extremities weakness or hemiplegia due to pyramidal tract injury
      occurring in 75.0% cases of control group whereas only 20.0% patients in trial
      group (P < 0.01). The mean Karnofsky scale were 69.58 +/- 23.49 and 84.80 +/-
      23.49 respectively in control and trial groups (P < 0.05). The excellent outcome
      ratio (Karnofsky scale = 90 - 100) was 37.5% in control group and 72.0% in trial
      group respectively (P < 0.05). CONCLUSIONS: DTI allows individual estimation of
      large fiber tracts of brain. Furthermore, to integrate spatial three-dimensional
      information concerning the white matter tracts into traditional neuronavigation
      images during surgery, was valuable in presenting topographical character of
      involving (shift or erosive) pyramidal tracts and relationship with the margins
      of neighboring tumors. The mapping of large fiber tracts was a safe, efficient,
      reliable technique. DTI should be routinely used in neuronavigation surgery of
      brain tumor involving pyramidal tracts to plan the optimal trajectory and ensure
      total resection of the lesions during operation, as well as to decrease potential
      disability after operation and to shorten the length of hospitalization.

PMID- 14680565
TI  - [MRI-guided stereotactic biopsy for questionable diseases in brain].
AB  - OBJECTIVE: To explore the accuracy and role of magnetic resonance imagine (MRI)
      guided stereotactic biopsy for atypical diseases in brain. METHODS: Using MRI
      volume scan and multiplane reconstruction, MRI-guided stereotactic brain biopsies
      were performed with CRW stereotactia frame in twenty-six patients whose lesions
      were atypical or unable to be detected by CT scanning. RESULTS: No serious
      complication (intracranial hematoma, paralysis) caused by brain biopsy was found
      in all twenty-six patients. Definite pathologic diagnosis and appropriate
      treatment were given to these patients. The lesions included gliomatosis cerebri,
      brain cysticercosis and Krabbe's disease, et al. CONCLUSIONS: MRI-guided
      stereotactic brain biopsy is more accurate for pathological diagnosis than CT
      guided stereotactic brain biopsy. MRI-guided stereotactic biopsy can provide
      reliable diagnosis and treatment especially for the questionable lesions in
      brain.

PMID- 14680566
TI  - [Surgical techniques for the ureterointestinal anastomosis in continent urinary
      diversion].
AB  - OBJECTIVE: To compare the complications of direct and antirefluxing techniques of
      ureterointestinal anastomosis in continent urinary diversion. METHODS: Sixty
      three patients underwent continent urinary diversion. Twenty-four patients were
      treated by the direct ureteroenteric anastomosis and the others treated by the
      antirefluxing technique. The follow up studies included following-up the
      information of ureteric stricture, ureteric reflux, renal function and acute
      urinary infection. It was assessed for 3 months to 6 years with a mean follow up
      of 26 months after operation. RESULTS: Of 78 ureters reimplanted using
      antirefluxing technique. A total of 12 ureters had anastomotic stricture
      formation postoperatively. Only one of 48 ureters reimplanted using direct
      anastomoses had anastomotic stricture. The difference between the direct and
      antirefluxing technique groups was remarkable (chi2 = 4.375, P < 0.05).
      Furthermore, there was no significant difference between the direct and
      antirefluxing technique groups in regard to ureteric reflux, renal function and
      acute urinary infection. CONCLUSIONS: Antirefluxing anastomoses resulted in
      obviously higher rate of ureterointestinal anastomotic stricture in comparison
      with the direct anastomosis. The direct ureteroenteric anastomosis may be the
      suitable choice for patients undergoing continent urinary diversion.

PMID- 14680567
TI  - [Expression of human TRAIL gene in COS-7 cells and its effects in the treatment
      of hepatic carcinoma].
AB  - OBJECTIVE: To study the therapeutic potential of TRAIL and in combination with
      subtoxic level of chemotherapeutic agents in the treatment of human
      hepatocellular carcinomas (HCCs). METHODS: The plasmid pcDNA 3.0-hTRAIL was
      transfected into COS-7 cells, and it was transiently expressed. The cytotoxic
      functions of the expressed product and in combination with chemotherapeutic
      agents were detected. RESULTS: The transiently transfected COS-7 could express
      the active human TRAIL. It had mild cytotoxic functions on HCC cell lines. The
      cytotoxicity rates in both cell lines were 9.2% and 9.5% respectively.
      Chemotherapeutic agents, mitomycin (M), 5-FU and actinomycin D (AcD) dramatically
      augmented TRAIL induced cytotoxic function. There were significant differences in
      the cytotoxicity between the use of single agent and in combination with TRAIL
      (TRAIL + M, M; 60.1%, 32.6%, TRAIL + 5-FU, 5-FU: 68.1%, 29.2%, TRAIL + AcD, AcD;
      72.9%, 58.6%) (P < 0.05). CONCLUSIONS: The combination of human TRAIL and
      chemotherapeutic agents, such as mitomycin, 5-FU and actinomycin D, seemed to
      exert a synergistic effect compared with either agent alone, and it might have
      therapeutic potential in the treatment of human HCC.

PMID- 14680568
TI  - [To set up a mdrl multidrug resistant model of orthotopic transplantation of
      liver carcinoma in nude mice].
AB  - OBJECTIVE: To set up a mdr1 multidrug resistant model of orthotopic
      transplantation of liver carcinoma in nude mice by intermittent abdominal
      chemotherapy. METHODS: The hepatocellular carcinoma cell line HepG2 was first
      cultured, then subcutaneous carcinoma was produced to form the tumor donor mice.
      An orthotopic mdr1 hepatoma was produced by implanting the tumor fragment
      subserosally to the mice liver, and intermittent chemotherapy with Pharmorubicin
      given to induce drug resistance. Physical examination, ultrasonography, spiral CT
      and laparotomy were used to examine the growth of the tumor. RT-PCR and SP method
      by the monoclonal antibody JSB-1 were adoped to detect the expression of mdr1
      mRNA and p-gp protein. RESULTS: There was no mortality. The successful rate of
      tumor implantation is 88% (22/25), the successful rate of supplementary
      implantation was 100% (3/3), and the successful rate of induction of drug
      resistance was 80% (16/20). The expressions of mdr1-mRNA and p-gp in the
      Pharmorubicin group were 23 folds and 13 folds of the control group,
      respectively. CONCLUSIONS: The nude mice mdr1 multidrug resistant model of
      orthotopic liver carcinoma were set up successfully, with its features similar to
      clinical cases. It would be helpful for the further study of the diagnosis and
      reversal strategy of the MDR phenomenon.

PMID- 14680569
TI  - [Experimental study on constructing small-caliber artery by tissue engineering
      approach].
AB  - OBJECTIVE: To investigate the possibility of constructing small-caliber artery by
      means of tissue engineering. METHODS: Cell-PGA mixtures were made by separately
      seeding 1 x 10(7) smooth muscle cells and 5 x 10(6) endothelial cells isolated
      from neonate umbilicus onto PGA scaffold, the cell-PGA constructs were wrapped
      around a silicone tube before its implantation subcutaneously to nude mice and
      the mice were sacrificed in 2 and 6 weeks. The tissue engineered artery (TEA)
      were examined both grossly and immunohistochemically. RESULTS: The gross
      appearance of TEA was similar to that of the natural counterparts; histologic and
      immunohistochemical analyses of the neoformed tissues revealed a typical artery
      structure, including the presence of EC at the luminal surface and the presence
      of SMC and collagen in the wall. CONCLUSION: TEA with histology similar to
      natural vessel can be constructed by tissue engineering.

PMID- 14680570
TI  - [The effect of nuclear transcription factor-kappaB decoy oligodeoxynucleotides on
      the intimal hyperplasia in vein graft].
AB  - OBJECTIVE: To investigate the effect of nuclear transcription factor-kappaB decoy
      oligodeoxynucleotides (NFkappaB decoyODNs) on the intimal hyperplasia (IH) in
      vein graft in rats. METHODS: Autogenous vein graft model for 72 Wistar rats was
      established, and the interior jugular vein was transplanted to common jugular
      artery by microsurgical technique. The rats were divided into 6 groups according
      to different processing methods, including NFkappaB decoyODNs 50 microg and 200
      microg, scramble decoyODNs 50 microg and 200 microg, control and lipofectin +
      pluronic teams. Vein graft samples were harvested in 1 or 2 weeks after surgery
      and ICAM-1 mRNA were measured by RT-PCR. Western blotting and
      immunohistochemistry methods were also employed to detect the expression of p65
      and ICAM-1. IH was compared at the same time. RESULTS: The intimal hyperplasia
      was evident in 1 or 2 weeks after vein graft, and ameliorated by 50 microg of
      NFkappaB decoyODNs with inhibition rate from 22% to 31%, 200 microg of NFkappaB
      decoyODNs had a higher inhibition rate from 41% to 53%. However, no effect was
      found in the other teams. The expression of ICAM-1 mRNA was also inhibited
      significantly by NFkappaB decoyODNs and more obvious in 2 weeks after surgery.
      Expression of ICAM-1 and p65 decreased greatly in NFkappaB decoyODNs team, which
      has a inhibition rate from 30% to 57%. CONCLUSION: Transfection of NFkappaB
      decoyODNs can inhibit the IH after vein graft, which may be accomplished by the
      inhibition of gene expression of ICAM-1.

PMID- 14680571
TI  - [Effect of the biodegradable chitosan external stent on the early changes in the
      rabbit vein grafts].
AB  - OBJECTIVES: To investigate the effect of chitosan biodegradable external stent
      (CES) on the early changes of rabbit vein graft (VG). METHODS: Rabbit vein
      grafting models were divided into S group (with perivenous CES) and NS group
      (without perivenous CES). The VG were harvested in 1 week, 2 weeks, 4 weeks after
      operation, respectively. The expression of proliferating cell nuclear antigen
      (PCNA) was used for evaluating the proliferation of the smooth muscle cell (SMC).
      The thickness, area of neointima and media of the VG were calculated by computer
      imaging analysis system. RESULTS: CES began to degrade in 2 weeks after
      operation. The thickness, area of both neointima and media of the VG in S group,
      increased mildly in 1 week after operation, and kept steady in 1 or 2 weeks after
      grafting, which was significantly less than NS group (both P < 0.01), then
      increased mildly in 4 weeks after grafting but still less than NS group (P <
      0.05). The expression of PCNA of SMC decreased significantly in comparison with
      NS group though increasing mildly in four weeks after operation. Both neointimal
      formation and cell proliferation in the graft wall were significantly reduced by
      external stenting as compared to the results with unstented grafts. CONCLUSIONS:
      CES may reduce early intimal and medial hyperplasia, and may be beneficial in
      improving the long term patency of the VG. The biodegradable characteristics of
      the CES may influence its effect.

PMID- 14680572
TI  - [Chronic sheep modal for pulmonary valve implantation with domestic bileaflet
      mechanical prosthesis].
AB  - OBJECTIVE: The aim of this study was to identify the long-term character of the
      domestic bileaflet mechanical valve in the chronic implanted sheep model and to
      evaluate the potential value of the modal. METHODS: Six adult sheep underwent
      implanted mechanical bileaflet valve in pulmonary position under the cardio
      pulmonary bypass with beating heart. The chronic implanted sheep model was built
      up and observed in the respects of a long-term survival, function of prosthesis
      and pathological specimen. RESULTS: Six adult sheep survived with good condition
      after operation. The average survival period of six sheep was (221 +/- 208) days.
      Two sheep were postoperatively sacrificed in 41 and 71 days, respectively. The
      necropsy revealed normal valve function without thrombosis, periprosthetic
      leakage and overgrowth of fibrous tissue. One sheep died from dysfunction of
      prosthetic valve at the postoperative 196 days. The reason was the prosthetic
      thrombosis with slight overgrowth of fibrous tissue in periprosthesis. The other
      two sheep died from severe anemia at the postoperative 196 days and 234 days, and
      the autopsy revealed no abnormal finding else. And one remained to survive with
      good condition up to now (over 617 days) and was checked by Doppler
      echocardiogram twice at the postoperative 438 days and 479 days, respectively.
      The results showed normal function of the bileaflet valve in pulmonary position.
      CONCLUSION: The long-term good effects would be achieved by using the implanted
      new domestic bileaflet valve in pulmonary position of sheep.

PMID- 14680573
TI  - [Temporomandibular joint disc displacement: diagnosis by arthrography with dental
      volumetric computerized tomography].
AB  - OBJECTIVE: Temporomandibular joint sideways and rotational disc displacement was
      assessed by arthrography with dental volumetric computerized tomography. METHODS:
      The study was conducted retrospectively on 119 joints of 109 patients (87
      females, 22 males, mean age 31.1 years), who had undergone arthrography with
      dental volumetric CT in the sagittal and coronal planes. The disc displacements
      were subdivided into 5 types; condylar abnormalities were subdivided into 4
      types. RESULTS: Complete anterior disc displacement was the commonest (70.6%) and
      medial the rarest (0.8%); anterolateral and anteromedial displacements were 18.5%
      and 10.1% respectively. The types of disc displacements were not correlated with
      bone lesions. A higher prevalences of bone lesions were found in the lateral
      poles of condyles. CONCLUSIONS: Arthrography using dental volume CT can be taken
      in the sagittal and coronal planes, so the sideways and rotational disc
      displacements, perforations and bone lesions can be evaluated. It's superior to
      conventional arthrography.

PMID- 14680574
TI  - [Evaluation of the use of dental operating microscope and ultrasonic instruments
      in the management of blocked canals].
AB  - OBJECTIVE: To evaluate the use of dental operating microscope (DOM) and
      ultrasonic instruments in treating blocked canals. METHODS: 135 blocked canals in
      92 teeth were treated with ultrasonic tips and files under DOM. The etiology of
      canal blockage included calcification, broken instruments, post, resinifying
      therapy or ledge. These canals were negotiated and root canal therapy or
      pretreatment was performed. The success rates were calculated. RESULTS: 77 teeth
      were successfully managed with a success rate of 83.7%. 84.4% of the blocked
      canals were negotiated. The success rates of each category of the blocked canals
      were: 88.1% for calcified canals; 76.9% for canals blocked by instrument
      fragments; 100% for canals blocked by post; 81.1% for canals subjected to
      resinifying therapy; and 78.6% for ledged canals. Complications such as root
      canal perforation or vertical fracture did not occur. CONCLUSION: The use of DOM
      and ultrasonic instruments is proved to be an effective way in the management of
      blocked canals.

PMID- 14680575
TI  - [The relationship between Helicobacter pylori in oral cavity and the Hp infection
      in stomach].
AB  - OBJECTIVE: To analyze the relationship between Helicobacter pylori (Hp) in oral
      cavity and the Hp infection in stomach. METHODS: 102 patients with gastric Hp
      infection and periodontitis were enrolled in this study. DNA was extracted from
      subgingival plaques, mouthwashes and stomach mucosa samples by using the glass
      milk (SiO2) purification method. To identify the presence of Hp in these samples,
      PCR (polymerase chain reaction) was carried out, and two pairs of oligonucleotide
      primer were used to amplify a portion of gene urease C and gene cag A of Hp.
      RESULTS: The rate of Hp detected in oral cavity was significantly higher in
      patients with positive Hp in stomach (43.1%, n=58) than in those with negative Hp
      in stomach (22.7%, n=44, P<0.05). After the treatment for gastric Hp infection
      for 4 weeks, the eradication rate of Hp in stomach was lower, but only slightly
      in patients with positive oral Hp (16/25, 64%) than in those with negative oral
      Hp (24/33, 72.7%). However, this difference became apparent (36.0% vs 63.6%,
      P<0.05) after one year of the treatment. CONCLUSIONS: The effectiveness of the
      eradication therapy for gastric Hp infection is affected by the presence of Hp in
      oral cavity. Oral colonization of Hp may imply that there is a risk of the
      relapses of gastric and duodenal Hp infection and ulcer after the antibiotics
      treatment for the eradication of Hp.

PMID- 14680576
TI  - [The effect of tooth preparation design on the CAD/CAM all-ceramic coping crown's
      fitness].
AB  - OBJECTIVE: To study the effect of tooth preparation design on fitness of CAD/CAM
      all-ceramic coping crown. METHODS: The tooth preparation comprised 2 types of
      occlusal convergence (10 degrees, 20 degrees), 2 margin forms (shoulder,
      chamfer). The MC coping were milled by Cerec 2 CAD/CAM system, cemented,
      embedded, sectioned, and measured at 10 sites to obtain the data of margin,
      shoulder, axial surface, occlusal surface fitness. RESULTS: The coping's fitness
      was influenced by convergence angle and margin form. The coping's fitness was
      very nice (101.7 approximately 127.9) microm when the coping with 20 degrees
      occlusal convergence angle. Those coping with 20 degrees occlusal convergence and
      chamfer margin in tooth preparation provided the best fitness, its cement film
      thickness in margin was (40.1 +/- 11.8) microm. CONCLUSIONS: The 20 degrees
      occlusal convergence and chamfer margin can be used for CAD/CAM all-ceramic crown
      in clinical application.

PMID- 14680577
TI  - [Reconstruction of segmental mandibular defect of canine using titanium-nickel
      distractor].
AB  - OBJECTIVE: To establish a continuous and automatic distraction osteogenesis
      technique in reconstruction of segmental mandibular defect by using embedded
      titanium-nickel alloy distractor with characteristics of shape-memory and super
      elasticity. METHODS: Adult hybrid canines were used as the animal model.
      Segmental defects of 1-3 cm in the body of mandible were created by surgical
      osteotomy. Bi-focal distraction osteogenesis was applied using embedded titanium
      nickel distractor designed by the authors. The canines were sacrificed 3 months
      after the operation and the mandibles were harvested to examine the results of
      bone regeneration. RESULTS: The histocompatibility of titanium-nickel distractors
      was good. Distraction osteogenesis was completed automatically and the defects
      were elementarily restored. Radiological and histological examination showed well
      bone regeneration in distraction area. CONCLUSIONS: Distraction osteogenesis
      using embedded self-loading titanium-nickel distractor could be a hopeful and
      useful technique. It might help to solve the problems of functional mandibular
      reconstruction in the near future.

PMID- 14680578
TI  - [The beneficial effect of genistein on mandible bone metabolism in ovariectomized
      rats].
AB  - OBJECTIVE: To detect the effect of genistein on mandible metabolism in
      ovariectomized rats. METHODS: Forty 12 week-old female SD rats were randomly
      assigned to four groups: (1) sham operated; (2) ovariectomized; (3)
      ovariectomized and treated with estradiol; (4) ovariectomized and received
      genistein, 45 mg/kg body weight per day. After 12 weeks, bone mineral density
      (BMD), serum level of alkaline phosphatase (ALP), acid phosphatase (ACP),
      osteocalcin, IL-1beta, TNF-alpha, IL-6 and calcitonin (CT) were evaluated. In
      addition, the serum estradiol and the weight of uteri were also examined to
      indicate the side effect of genistein to the uteri. RESULTS: Ovariectomized
      animals had a significant decrease in BMD, and increased serum level of ALP, ACP,
      IL-1beta and osteocalcin compared with sham rats. After treated with genistein,
      BMD and the serum level of ALP, ACP, osteocalcin increased significantly, while
      the serum level of IL-1beta and TNF-alpha decreased. Especially, the increase of
      ALP and osteocalcin was higher than that of estradiol-treated animal.
      Additionally, the uterus weight index and the serum estradiol in genistein
      treated rats were lower significantly than those of estradiol-treated rats.
      CONCLUSIONS: Genistein can improve the mandible bone metabolism as well as its
      effect on femur through the promotion of bone formation and the prevention of
      bone resorption with slight side effect. Genistein provides an additional viable
      way to therapy for osteoporosis in the jaw bones.

PMID- 14680579
TI  - [The measurement and comparison of shear fracture strength and shear bond
      strength between carbon fiber post and some other posts].
AB  - OBJECTIVE: The shear fracture strengths of carbon fiber post, IPS-Empress 2 all
      ceramic post (without ZrO2 post), cast Ni-Cr alloy post, prefabricated zirconia
      ceramic post, human dentin and the shear bonding strengths of the first three
      kinds of post bonded in the human root canals were measured and compared, which
      are as the reference for dental clinic. METHODS: Standard cylindrical samples
      were made respectively in each group of carbon fiber post, IPS-Empress 2 all
      ceramic post, cast Ni-Cr alloy post, prefabricated zirconia ceramic post, human
      dentin, three for each group. The shear fracture strengths of these samples were
      measured by universal testing machine (AUTOGRAPH DCS5000). Standard cylindrical
      samples were made respectively in each group of carbon fiber post, IPS-Empress 2
      all-ceramic post (without ZrO2 post), cast Ni-Cr alloy post, five for each group.
      They were bonded in extracted human root canals that had been prepared to 3.0 mm
      length and 2.0 mm diameter with Glass ionomer cement (Japan Shofu). The shear
      bond strengths were measured by the same universal testing machine. RESULTS: The
      shear fracture strengths of the carbon fiber post (199MPa), cast Ni-Cr alloy post
      (210MPa, shear bend strength) and prefabricated zirconia ceramic post (193MPa)
      were statistically higher than those of IPS-Empress 2 all-ceramic post (109MPa)
      and human dentin (100MPa). The shear fracture strength of the carbon fiber post
      was statistically similar to that of cast Ni-Cr alloy post and prefabricated
      zirconia ceramic post. There were no statistical differences between the shear
      bond strengths of carbon fiber post (2.4MPa) and cast Ni-Cr alloy post (3.8MPa).
      IPS-Empress 2 all-ceramic post broke before debonding (2.7, break value).
      CONCLUSIONS: Carbon fiber post, as well as cast Ni-Cr alloy post and
      prefabricated zirconia ceramic post, has a comparatively high shear fracture
      strength. The shear bond strengths of carbon fiber post is similar to cast Ni-Cr
      alloy post.

PMID- 14680580
TI  - [Adhesion of oral microorganisms on dental porcelain polished and glazed].
AB  - OBJECTIVE: This study compared the roughness of porcelain polished or glazed
      surfaces and the adhesion of oral streptococcus mutans to them in vitro. METHODS:
      30 porcelain samples were made. Porcelain samples in group A were polished with
      diamond paste. Porcelain samples were glazed in group B and were polished with
      Al2O3 (240#) bur in group C. Their roughness values were measured by
      profilometer. Standardized cell suspensions were incubated with test samples for
      one hour at 37 degrees C, then retained cells were counted by image analysis
      (percentage area of a microscopic field covered by cells). RESULTS: Roughness
      values of group A, B, C were respectively (0.1987 +/- 0.057) microm, (0.1990 +/-
      0.091) microm, (0.4260 +/- 0.174) microm. There was no significantly difference
      between group A and group B. The roughness samples in group C were significantly
      rougher than that in the other groups. The amount of retained cells in group A,
      group B, group C was respectively (15.92 +/- 4.37)%, (16.39 +/- 6.31)% and (41.48
      +/- 12.1)%. There was no significant difference between the cell adhesion on
      porcelain surface glazed and polished, but more bacteria adhered on the porcelain
      surface in group C. CONCLUSIONS: Porcelain surface polished treatment was
      clinically acceptable compared with its glazed. They all exhibited the least
      amount of bacteria adhesion. The more porcelain surface was rough, the more
      bacteria adhered on it.

PMID- 14680581
TI  - [Relationships between periapical lesion and IL-1, TNF-alpha gene expression in
      rat].
AB  - OBJECTIVE: To understand the effects of the IL-1, TNF-alpha cytokines on the
      pathogenesis of periapical lesions by investigating its gene expression in rat.
      METHODS: The model was established by surgically exposing mandibular molar teeth
      and left open to permit infection from the oral environment. The SD rats were
      killed at 1, 2, 3, 4 weeks and mandibular molar teeth X-ray were taken. In situ
      hybridization was used to test IL-1alpha, IL-1beta, TNF-alpha mRNA expression in
      periapical area and the kinds of positive cells were identified. Using image
      analysis system analyzed gene expression semi-quantified. RESULTS: IL-1alpha, IL
      1beta and TNF-alpha mRNA were all expressed beginning at 1 week, peaked at 3
      weeks, and declined somewhat at 4 weeks, but IL-1beta mRNA was expressed at much
      lower levels with the same kinetics (P<0.01). Most of the staining occurred in
      areas that had heavy inflammatory infiltrate, fibroblasts, or endothelial cells.
      There was a statistically significant correlations between the area of periapical
      lesion and the number of positively stained cells for IL-1alpha and for TNF-alpha
      (IL-1alpha: r=0.875, P<0.001; TNF-alpha: r=0.858, P<0.001), and between the
      number of positive cells for IL-1alpha and that of for TNF-alpha (r=0.969,
      P<0.001). CONCLUSIONS: IL-1alpha and TNF-alpha genes are highly expressed in
      developing periapical lesions in rat, which supports the hypothesis that these
      two cytokines play a key role in pulpal and periapical pathogenesis, including
      the concomitant bone destruction.

PMID- 14680582
TI  - [Computed tomography diagnosis of maxillofacial and neck malignant tumors
      invading carotid artery].
AB  - OBJECTIVE: To evaluate the diagnostic value of the carotid artery invasion by the
      oral-maxillofacial and neck malignant tumors with computed tomography (CT).
      METHODS: Fifty-three patients (55 tumors) of oral-maxillofacial and neck
      malignant tumors were examined with enhanced axial CT examination in pre
      operation. The CT manifestations of all tumors were retrospectively corresponded
      with the surgical findings. RESULTS: Oral-maxillofacial and neck malignant tumors
      with abnormal common carotid artery (CCA) or internal carotid artery (ICA)
      manifestations were shown on CT as five types: type I, compression and
      deformation of CCA or ICA in six tumors; type II, displacement of CCA or ICA in
      15 tumors; type III, the tumors encompass the carotid vessels more than 180
      degrees in 8 tumors; type IV, the segmental deletion of fat or fascia planes
      between tumor and CCA/ICA in 25 tumors; and type V, ill-defined CCA/ICA wall in
      12 tumors. Surgical findings recorded that 20 CCAs or ICAs were adhered by the
      oral-maxillofacial and neck malignant tumors. Of these 20 lesions, 14 malignant
      tumors (70%) with more than two abnormal changes of CCA or ICA were shown on CT
      images. The respective sensitivity, specificity and accuracy were 30.0%, 100.0%
      and 74.5% for type I, 20.0%, 68.6%, 50.9% for type II, 22.2%, 100.0%, 49.1% for
      type III, 90.0%, 80.0% and 83.6% for type IV, and 45.0%, 88.6% and 72.7% for type
      V. CONCLUSIONS: The main CT findings of maxillofacial and neck malignant tumors
      affecting the carotid artery are different. Comparatively, the signs of type I,
      type III and type IV may be valuable in evaluating CCA or ICA invasion, although
      the accurate diagnosis of the CCA or ICA involvement by the maxillofacial and
      neck malignant tumors remains difficult.

PMID- 14680583
TI  - [Antitumor effects of electrothermal and electrochemical therapy on mice with
      sarcoma180].
AB  - OBJECTIVE: To explore the anti-tumor effects and the mechanism of a new treatment
      for Sarcoma180 in mice using both hyperthermia (H) and electrochemical therapy
      (ECT). METHODS: A group of mice with Sarcoma180 (1 cm in diameter) were divided
      randomly into four groups and given different treatments: Control, ECT alone, H
      alone and electrothermal & electrochemical therapy (ETECT). The volumes of the
      tumors were calculated everyday after treatment. The tumor tissues were examined
      morphologically at 0, 6, 24 and 72 hours after treatment. RESULTS: The tumors
      treated with ETECT were completely destroyed, and did not recur within a period
      of ten days by pathological examination. Results of this group were significantly
      different with the other groups (P<0.01). However, recurred tumors were found in
      6 mice of H group and 5 mice of ECT group, respectively. CONCLUSIONS: Based on
      the results obtained, ETECT induced by ETECD (D-device) is an effective way to
      eliminate cancer. It is capable of completely destroying cancer cells in a short
      time. The rate of Sarcoma180 inhibition is 100%, and malignant cells can't recur.
      The research provided theoretical and experimental bases for the treatment of
      oral cancer by a new approach to treat oral cancer.

PMID- 14680584
TI  - [The formation of transgenic mice with hemangiomas].
AB  - OBJECTIVE: To set up the animal model of hemangioma by microinjecting the PyMT
      transgenic DNA. METHODS: Constructing the transgenic PyMT gene, and
      microinjecting it into fertilized embryos which were transferred to
      pseudopregnant recipients then. Observing the phenotype of the newborn-mice,
      detecting the integration of transgenic DNA by PCR, and analyzing the
      histological morphon of the neoplasm of the mice. RESULTS: The transgenic DNA was
      proved to be right and has been microinjected into 579 fertilized embryos, 62
      mice were born. Within the 62 mice, one mouse was found being the phenotype of
      hemangioma. PyMT gene was expressed in the total DNA of the transgenic mouse by
      PCR. CONCLUSION: It could be a good way to build animal model of hemangioma with
      transgenic PyMT DNA.

PMID- 14680585
TI  - [The study of apoptosis of salivary adenoid cystic carcinoma in nude mice].
AB  - OBJECTIVE: To study the feature of apoptosis of salivary adenoid cystic carcinoma
      (SACC) induced by recombined human tumor necrosis factor-alpha (rhTNF-alpha) in
      nude mice, and to evaluate the related genes expression of apoptosis. METHODS:
      Twelve SPF grade 4 approximately 5 weeks old female Balb/c nude mice were
      selected in this study. SACC-83 cells were collected to 6 x 10(7) per milliliter
      and injected subcutaneously. Group A and B were experimental group which was
      given 100 x 10(4) IU/kg TNF-alpha or 10 x 10(4) IU/kg TNF-alpha respectively.
      Group C was only given normal saline and used as normal control. The
      investigations were adopted by using both light and transmission electron
      microscope (LM and TEM), flow cytometer and In Situ Cell Death Detection Kit. The
      evaluations of bax and bcl-2 expression were utilized by immunohistochemistry.
      RESULTS: The percentage of apoptosis of transplanted tumors was much higher than
      that of the control (P<0.01). Apoptotic cells were calcified and grit bodies were
      formed. Apoptotic cells expressed and contained significantly higher proportions
      of both bax and bcl-2 proteins (P<0.05). CONCLUSIONS: It is suggested that
      calcification may be the obvious feature and the last outcome of the apoptosis of
      SACC transplanted tumors. Apoptosis induced by TNF-alpha can increase the
      expressions of bax and bcl-2.

PMID- 14680586
TI  - [The alteration of MTS1 gene in precancerous lesions and squamous cell carcinoma
      of oral mucosa].
AB  - OBJECTIVE: To investigate the expression and alteration (including homozygous
      deletion and mutation) of MTS1 gene in precancerous lesions and squamous cell
      carcinomas (SCC) of oral mucosa, and to analyse the function of MTS1 gene
      alteration in oral mucosal carcinogenesis. METHODS: The expression of p16 protein
      produced by MTS1 gene was examined with immunohistochemical SP method in 10
      normal oral mucosas, 30 precancerous lesions (10 mild, 10 moderate and 10 severe
      dysplasia respectively) and 45 squamous cell carcinomas (SCCI18, SCCII 19, SCCIII
      8). The deletion and mutation of exon1 and exon2 of MTS1 gene were examined with
      methods of PCR and SSCP in these same samples. RESULTS: All the precancerous
      lesions had p16 protein expression and no alteration of MTS1 gene. In SCC, the
      positive rate of p16 protein was 60.0% with 72.2% in SCCI, 57.9% in SCCII, 37.5%
      in SCC III, and there were no significant difference among the three groups by
      chi2 test (P>0.05). Gene homozygous deletion of exon1 and/or exon2 was detected
      in 10 cases, and gene mutation in 4 cases. The whole rate of gene alteration was
      31.1% (14/45). The MTS1 gene alteration rate was 27.8% in SCCI, 31.6% in SCCII,
      37.5% in SCC III and there was also no significant difference among the three
      groups by chi2 test (P>0.05). In SCC with local lymph nodes metastasis, MTS1
      alteration rate was 57.1%, while in SCC with no lymph nodes metastasis was 8.3%,
      and there was significant difference by chi2 test (P<0.05). CONCLUSIONS: MTS1
      gene alteration is not an early event in the carcinogenesis of oral mucosa and
      can not be used as a biology mark to examine oral precancerous lesions. MTS1 gene
      may play a certain role in the progression of oral squamous cell carcinomas.

PMID- 14680587
TI  - [The effect of periodontal initial therapy on circulating TNF-alpha and HbA1C in
      type 2 diabetes patients with periodontitis].
AB  - OBJECTIVE: To investigate the effect and mechanism of periodontal initial therapy
      on type 2 diabetes patients with periodontitis. METHODS: 15 type 2 diabetes
      patients with periodontitis were selected. Their body mass index (BMI), sulcus
      bleeding index (SBI), probing depth (PD), circulating tumor necrosis factor-alpha
      (TNF-alpha) concentration, and the value of glycosylated hemoglobin (HbA1C),
      triglycerides (TG) and cholesterol (CHOL) were assessed respectively before and 4
      6 weeks after periodontal initial therapy. RESULTS: After initial therapy, SBI,
      PD, circulating TNF-alpha concentration, and the value of HbA1C and TG were
      reduced significantly (P<0.05), while there were no significant differences in
      BMI and CHOL value (P>0.05). CONCLUSIONS: Periodontal initial therapy can
      effectively reduce HbA1C value in type 2 diabetes patients with periodontitis,
      possibly through the reduction of circulating TNF-alpha concentration.

PMID- 14680588
TI  - [Effects of tobacco on proliferation and attachment of human periodontal ligament
      fibroblast].
AB  - OBJECTIVE: To evaluate the effects of nicotine and tobacco extract (ST) on PDLFs
      morphology, structure, proliferation and attachment. METHODS: PDLFs were cultured
      in the presence of nicotine and ST at various concentration. The cell changes in
      the morphology and structure were examined by histological and transmission
      electrical microscope (TEM). The growth and attachment of cell were measured by
      MTT method. RESULTS: The size of the cells became smaller gradually and their
      shapes changed from shuttle type to oval or round when the concentration of
      nicotine and ST increased, the polarity of the cells was in disorder,
      ultrastructure showed that the organelles, especially rough-surfaced endoplasmic
      reticulum and golgi complex decreased in number, microtubule and microfilaments
      were disassembled, the nuclei became fewer or shrunk, the growth and attachment
      were dose-dependently inhibited. CONCLUSIONS: Nicotine and ST can change PDLFs'
      morphology and structure, they may inhibit the growth and attachment through
      disruption of the cytoskeleton, suggesting nicotine and ST may have pathological
      role on human periodontitis.

PMID- 14680589
TI  - [The association between interleukin-1 receptor antagonist genotype and chronic
      periodontitis of Uighur patients].
AB  - OBJECTIVE: To investigate interleukin-1 receptor antagonist (IL-1ra) genotype and
      its association with the susceptibility of chronic periodontitis in Uighur
      patients of Xinjiang. METHODS: Genomic DNA was obtained from buccal swabs of 41
      subjects with severe chronic periodontitis (CP), 43 subjects with moderate CP, 49
      subjects with mild CP and 92 ethnically matched healthy control individuals.
      Genotypes of IL-1RN intron 2 VNTR was analyzed by SSP-PCR method. Then compared
      the differences in distribution of each genotype. RESULTS: A significant over
      representation of IL-1RN intron 2 VNTR allele 2 was found in severe chronic
      periodontitis group. CONCLUSION: IL-1RN intron 2 VNTR allele 2 may be a risk
      indicator for the susceptibility of severe chronic periodontitis in Uighur
      patients of Xinjiang.

PMID- 14680590
TI  - [Effect of elastic stress on expression of corebinding factor a 1 mRNA in human
      periodontal ligament cells in vitro].
AB  - OBJECTIVE: To investigate the osteoblast-like characteristics of human
      periodontal ligament cells affected by elastic stress in vitro, and the role of
      corebinding factor a 1 (cbfa1) in alveolar bone formation during orthodontic
      tooth movement. METHODS: Rat dig-labeled cbfa1 cDNA probe was prepared from SD
      rat osteoblasts cultured in vitro. Human periodontal ligament cells were cultured
      on the elastic bottom plate and stimulated by elastic stress using mechanical
      loading system for cultured cells in vitro. The expression of cbfa1 mRNA was
      detected by in situ hybridization method. RESULTS: Cbfa1 mRNA express in human
      periodontal ligament cells stimulated by elastic stress and did not express in
      normal human periodontal ligament cells. CONCLUSION: It is suggested that elastic
      stress plays a role in the differentiation process from human periodontal
      ligament cells to osteoblast-like cells. Cbfa1 is a transcription factor in
      alveolar bone remodeling during orthodontic tooth movement.

PMID- 14680591
TI  - [The relationship between the changes of upper airway and genioglossus muscle
      activity after the treatment with Snoreguard].
AB  - OBJECTIVE: To investigate the relationship between the changes of upper airway
      and genioglossus muscle activity after the treatment with Snoreguard. METHODS: 31
      patients with OSAS or snoring were treated with Snoreguard Cephalometric analysis
      was carried out to compare the changes of the upper airway before and after the
      treatment. The relationship between the change in morphology and that of
      genioglossus muscle activity among 22 patients was investigated. RESULTS: (1) The
      size of upper airway decreased significantly with Snoreguard. SPP-SPPW increased
      from (9.14 +/- 3.79) mm to (12.36 +/- 3.74) mm and TB-TPPW increased from (10.63
      +/- 3.71) mm to (11.90 +/- 4.33) mm. UC-LC decreased from (21.96 +/- 11.06) mm to
      (10.48 +/- 8.55) mm and H-MP decreased from (20.60 +/- 6.65) mm to (11.01 +/-
      6.84) mm. (2) The size of upper airway in part of the patients decreased with
      Snoreguard, but good treatment efficiency remained. CONCLUSION: The mechanism of
      Snoreguard is caused by the mechanical enlargement of upper airway.

PMID- 14680592
TI  - [Stability of teeth alignment after orthodontic treatment].
AB  - OBJECTIVE: To investigate the relapse of incisor alignment after orthodontic
      treatment and possible factors which may related to its stability. METHODS: 72
      finished cases with full records selected from orthodontic clinic of Peking
      University School of Stomatology composed the sample. The follow-up lateral head
      films and study casts were taken at least 2 years after orthodontic treatment.
      The cephalograms were measured by computerized program and the study casts
      measured by caliper. RESULTS: The upper Irregularity Index decreased from (11.5
      +/- 5.02) mm before treatment to (2.01 +/- 1.39) mm after treatment and then
      increased to (3.46 +/- 1.69) mm in the follow-up stage. The lower Irregularity
      Index decreased from (7.24 +/- 44.35) mm before treatment to (1.75 +/- 1.04) mm
      after treatment and then increased to (3.39 +/- 1.78) mm in the follow-up stage.
      The changes are significant statistically. The changes of jaw in the sagittal and
      vertical directions as well as the related changes of the position of lower
      incisors, the decrease of the lower canine arch width, Bolton Index and sex all
      have statistically significant relation with the changes of the lower
      Irregularity Index after retention. CONCLUSIONS: Compared with lower arch, the
      alignment in upper arch is more stable in the follow-up stage. The results
      suggest that some possible factors may have correlations with the change of lower
      arch crowding during the follow-up stage.

PMID- 14680593
TI  - [A study on the relationship between urinary 1-hydroxypyrene level and early
      genetic effect among coke oven workers].
AB  - OBJECTIVE: To investigate the relationship between the urinary 1-hydroxypyrene
      level and cytokinesis-block micronucleus and the olive moment of comet assay in
      peripheral blood lymphocyte in coke oven workers. METHODS: One hundred and thirty
      three workers from a coke plant and 28 referents without occupational PAH
      exposure were recruited in this study. Urinary level of 1-hydroxypyrene was
      measured by alkaline hydrolysis combined with high performance liquid
      chromatography as an internal exposure dose, and the DNA and chromosomal damage
      of peripheral blood lymphocyte were evaluated with comet assay and cytokinesis
      block micronucleus method. Personal information including occupational history,
      age, sex, smoking and alcohol drinking, was collected by questionnaire. RESULTS:
      There existed a good correlationship between the urinary level of 1-hydroxypyrene
      and frequency of micronuclei per 1 000 binucleated cells or the olive moment of
      comet assay in the study subjects, after adjusting for sex, age, smoking and
      alcohol drinking (r > 0.25, P < 0.01). One hundred and sixty-one subjects were
      divided into three groups by their urine 1-hydroxypyrene level (expressed as 0.30
      - 2.44, 2.45 - 7.09 and 7.10 - 33.10 micro mol/mol Cr), and the geometric means
      of their urinary levels of 1-hydroxypyrene were 1.14, 4.32 and 12.49 micro
      mol/mol Cr, respectively. After adjusting for age, sex, smoking and alcohol
      drinking by multiple nonparametric analysis of covariance, the median of olive
      moment of comet assay in the group of 7.10 - 33.10 micro mol/mol Cr was 3.67,
      significantly higher than that in the groups of 0.30 - 2.44 and 2.45 - 7.09; and
      the micronuclei frequencies in the groups of 2.45 - 7.09 and 7.10 - 33.10 micro
      mol/mol Cr were 8.00 per thousand and 7.50 per thousand, respectively,
      significantly higher than that in the group of 0.30 - 2.44 micro mol/mol Cr (6.00
      per thousand ). CONCLUSIONS: The comet assay of peripheral blood lymphocyte was
      more suitable to detect the PAHs-induced early genotoxicity, than the cytokinesis
      block micronucleus.

PMID- 14680594
TI  - [Ecological surveillance on breeding ground for Oncomelania hupensis snails in
      the areas prevalent with islet-type schistosomiasis using remote sensing
      technology].
AB  - OBJECTIVE: To probe rational indices suitable for ecological surveillance on
      breeding ground for Oncomelania hupensis snails in areas prevalent with islet
      type schisitosomiasis using remote sensing technology. METHODS: Three adjacent
      islets, prevalent with islet-type schistosomiasis, along the Yangtze River within
      the boundaries of Dongzhi County, Anhui Province were selected as study field for
      remote sensing analysis. Multi-spectral data were composed and non-supervisedly
      classified in computer with Idisi software for remote sensing analysis. Values of
      the normalized difference vegetation index (NDVI), green vegetation index (GVI),
      bright index (BI), which reflect the greenness and brightness of landscape, were
      also calculated. Finally, all the results were comprehensively analyzed, combined
      with data from the field investigation. RESULTS: NDVI, GVI and BI could depict
      characteristics of the landscape quantitatively. Values of NDVI, BI and GVI were
      varied in different types of landscapes, and 95% confidence interval of these
      values suitable for breeding of snails was 0.0522 approximately 0.3566, 2.4162
      approximately 28.2672 and 29.3404 approximately 40.3135, respectively.
      Classification of NDVI showed that type 5 anf type 6 were main breeding ground
      for snails, and type 4 with values of NDVI from 0 to 0.1 was potential areas for
      snail propagation. Classification of GVI showed that types 5, 6 and 7 were main
      breeding ground for snails, and also type 4 with values of GVI from 2 to 10 was
      potential areas for snail propagation. Both NDVI and GVI showed type 2 and type 3
      were temporarily not suitable for snail breeding. CONCLUSION: Index figures of
      NDVI and GVI re-formed by reasonable classification could reflect not only
      breeding ground for snails and range of the areas for snail propagation in
      islets, but also their evolving rules, i.e., status of new marshland formation
      and vegetation growth.

PMID- 14680595
TI  - [Antitransforming activity of chlorophyllin against trans-benzo(a)pyrene-trans
      7,8-dihydrodiol-9,10-epoxide].
AB  - OBJECTIVE: To study the inhibitory effect of chlorophyllin (CHL) on trans
      benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide (BPDE) induced malignant
      transformation in human bronchial epithelial cell line (16HBE). METHODS: 10, 50
      or 100 micro mol/L CHL were added into the media during the cells transformation
      induced by BPDE, and the malignant degree of transformed cells were identified by
      the ConA agglutination test and the assay for anchorage-independent growth and
      tumorigenicity. RESULTS: After the cells were cultured for 25 times, the time of
      cells agglutination in groups treated with both CHL and BPDE was increased
      significantly; the colony formation efficiency in soft agar in groups treated
      with both CHL and BPDE (7.4 per thousand, 11.4 per thousand and 14.4 per thousand
      ) showed significant decrease (P < 0.05) in dose-dependent manner, as compared
      with that in group treated with BPDE alone (19.6 per thousand ). Cells treated
      with both CHL and BPDE or BPDE alone developed tumor in nude mice, a squamous
      carcinoma confirmed by histopathological examination. The volume of tumor in
      groups treated with both CHL and BPDE (0.43 +/- 0.13) cm(2), (0.22 +/- 0.04)
      cm(2) and (0.10 +/- 0.06) cm(3) was significantly smaller (P < 0.05) and dose
      dependent, as compared with that in the group treated with BPDE alone (1.71 +/-
      0.37) cm(3). CONCLUSION: CHL showed significant antitransforming ability in human
      bronchial epithelial cell line induced by BPDE.

PMID- 14680596
TI  - [Sex distribution of neural tube defects and their birth outcome in high- and low
      prevalence areas of China].
AB  - OBJECTIVE: To describe and analyze epidemiological characteristics of babies with
      neural tube defects (NTD) by sex and birth outcome in a high-prevalence and a low
      prevalence areas of China. METHODS: Birth defects surveillance data collected
      from 1992 through 1994, as a part of the Sino-American cooperative project on NTD
      prevention, were used to classify NTD as four categories, i.e., anencephaly,
      encephalocele, high-level and low-level spina bifida according to the sites of
      lesion (high vs. low level lesion were cervicothoracic and lumbosacral,
      respectively). Each category was sub-classified, according to single or compound
      defect, as isolated external defects (including those with NTD only) or multiple
      external defects (including those with NTD and another major external birth
      defects that is not the sequence of a defect such as cleft lip with or without
      cleft palate). The rates of anencephalus, encephalocele, high- and low-level
      spina bifida (SB) in males and females and their sex ratios were calculated,
      adjusted for urban and rural areas, season, category and birth outcome by sex and
      sites of lesions (high vs. low). RESULTS: Totally, 784 NTD cases were identified
      from 326 874 recorded births (including live births, stillbirths and fetal deaths
      with a gestation age of at least 20 weeks). The prevalence rates of anencephalus
      (1.30 per 1 000 female births) and high-level SB (3.99) in females were higher
      than those (0.66 and 1.66 per 1 000 male births) in males in the high-prevalence
      northern regions; with adjusted prevalence rates of females 1.8 - 2.1 times
      greater than those of males. In the low-prevalence southern regions, the
      prevalence of high- (0.32 per 1 000 female births) and low-level SB (0.21) in
      female were higher than those in males, with high- and low-level SB rate of 0.10
      and 0.09 per 1 000 male births), with adjusted rates for females of 1.3 - 1.6
      times higher than in males. Isolated NTD accounted for more than 80% of all NTD
      cases, and the prevalence of isolated NTD in females (2.57) was higher than that
      in males (1.40). CONCLUSIONS: The sex differences in NTD existed between north
      and south, in accordance with the phenotype of NTD. It suggested that proportion
      of high level SB and anencephalus in females could increase as the prevalence of
      NTD going up, anencephaly, high- and low-level SB had the different genetic and
      environmental background.

PMID- 14680597
TI  - [An analysis of related factors for maternal mortality rate at county level].
AB  - OBJECTIVE: Data collected during a period of six years in implementation of the
      Health VI Project sponsored by the World Bank were used to analyze maternal
      mortality rates (MMR) at county level and its related factors, so as to decrease
      MMR further. METHODS: Routine data on maternal deaths, as well as its related
      economic, social and cultural factors, during 1995 to 2000 were collected at
      county level, and univariate analysis was conducted for them. RESULTS: Average
      MMR reduced remakably by 51.33% from 159.74/100 000 in 1995 to 77.75/100 000 in
      2000 in the areas with implementation of the Health VI Project. However, there
      was still a gap in MMR between the Project areas and the nation as a whole. MMR
      correlated with local topography, economic and cultural levels, traffic and
      communication, health resource, and quality of obstetric care service.
      CONCLUSIONS: In order to lower MMR further, it is necessary to increase financial
      investment for health, to improve health care service establishments, to
      strengthen health education for pregnant women and to increase their health
      awareness so as to improve their use of maternal care and health care services,
      to improve quality of obstetric care service, to strengthen training for health
      professionals and to improve their knowledge and skills, and to accelerate
      construction of traffic and communication.

PMID- 14680598
TI  - [Relation of body mass index and waist circumference with clustering of other
      risk factors for cardiovascular disease].
AB  - OBJECTIVE: To assess the relationship of body mass index (BMI) and waist
      circumference (WC) with clustering of other risk factors for cardiovascular
      disease (CVD). METHODS: A total of 30 561 participants aged 35 - 59 from
      different parts of China were surveyed for risk factors of CVD in two independent
      cross-sectional studies carried out in 1992 - 1994 and 1998. Data were pooled to
      analyze clustering rate of risk factors for CVD and relative risk of their
      clustering at varied levels of BMI and WC. Clustering of other risk factors for
      CVD was defined as any participant who had any two or more risk factors, such as
      high blood pressure, high serum total cholesterol, low HDL-C, high fasting plasma
      glucose. Clustering rate of other risk factors for CVD at different levels of BMI
      and WC was estimated. RESULTS: Clustering rate of other risk factors for CVD
      significantly increased with rising of BMI and WC. In most of varied BMI groups,
      clustering rate of other risk factor increased with rise of WC in both men and
      women (P value for trend < 0.05), and in most of varied WC groups, clustering
      rate of other risk factor significantly increased with rise of BMI (P value for
      trend < 0.05). Clustering rate of other risk factors for CVD adjusted for age was
      11.1% and 10.4% with BMI < 24.0 kg/m(2) and WC < 85/80 cm, 24.0% and 17.0% with
      BMI of 24 - 27.9 kg/m(2) and WC < 85/80 cm, 34.3% and 24.0% with BMI of 24 - 27.9
      kg/m(2) and WC of 85 - 95.9/80 - 89.9 cm, 40.8% and 29.6% with BMI of 24 - 27.9
      kg/m(2) and WC >/= 95/90 cm, 44.2% and 29.9% with BMI >/= 28 kg/m(2) and WC of 85
      - 95.9/80 - 89.9 cm, and 54.7% and 35.4% with BMI >/= 28 kg/m(2) and WC >/= 95/90
      cm, for men and women, respectively. CONCLUSIONS: BMI and WC were independently
      and positively associated with clustering rate of other risk factors for CVD. It
      is very important for health to keep both BMI and WC in normal level.

PMID- 14680599
TI  - [Studies on use and residue levels of pesticides in fruit and vegetable in
      Tianjin Area and its control measures].
AB  - OBJECTIVE: To investigate pesticide abuse on fruits and vegetables in Tianjin
      Area, to detect pesticide residues in fruits and vegetables, to study the methods
      for reducing pesticide residues in fruits and vegetables. METHODS: (1) A
      questionnaire on the pesticide application during growing fruit and vegetable was
      administered to 185 farmers in Tianjin Area. (2) According to the information
      from the questionnaire survey, fruit and vegetable samples were collected in four
      seasons around the year and measured for organophosphorus pesticide residues by
      gas chromatography. (3) Fruit and vegetable samples contained pesticide residue
      were treated by scald, immersion in 0.15% and 0.30% detergent solution, immersion
      in pure water, peeling and cutting root and pesticide residues were measured
      before and after the treatment. RESULTS: The percentage of pesticide abuse in
      growing fruit and vegetable was 65.00% in Tianjin area, and 31.60% of the fruits
      and vegetable samples collected in summer were positive for high toxic
      organophosphorus pesticides. Significant decrease of pesticide residue in fruit
      and vegetable was found by scald, immersion in 0.15% and 0.30% detergent
      solution, as well as peeling and cutting root, and over 80.00% pesticide residue
      in the samples could be reduced by scald. CONCLUSIONS: It is necessary to
      strengthen pesticide abuse control and market surveillance and inspection, in
      order to reduce the harmful effects of pesticide residue in fruit and vegetables
      to human health.

PMID- 14680600
TI  - [Etiologic fraction and interaction of risk factors for primary hepatocellular
      carcinoma in Wenzhou, Zhejiang Province].
AB  - OBJECTIVE: To explore etiologic fraction (EF) and interaction of serum hepatitis
      B surface antigen (HBsAg) carriage and other risk factors for primary
      hepatocellular carcinoma (PHC) in Wenzhou, Zhejiang, China. METHODS: 1:1 matched
      case-control study was carried out in Wenzhou, with 180 cases of PHC and 180
      controls. EF and interactions of serum positive HBsAg [HBsAg(+)] and other risk
      factors for PHC were analyzed by Mantel-Haenszel stratified method and
      conditional multiple logistic regression. RESULTS: Serum HBsAg(+), poor economic
      status during the past five years, preferring intake of pickled vegetables,
      history of PHC in their first-degree relatives, and negative life events all were
      risk factors for PHC, with EFs of 0.728, 0.245, 0.224, 0.084, and 0.234,
      respectively. There existed interactions of HBsAg(+) with other risk factors,
      including poor economic status during the past five years, preferring intake of
      pickled vegetables, history of PHC in their first-degree relatives, and negative
      life events, with etiologic fractions attributable to interaction [EF (A x B)] of
      0.770, 0.630, 0.848, and 0.627, and indices of interaction of 0.789, 0.638,
      0.852, and 0.634, respectively. CONCLUSIONS: Main risk factor for PHC in Wenzhou,
      Zhejiang, China could include HBsAg(+), poor economic status during the past five
      years, preferring intake of pickled vegetables, history of PHC in their first
      degree relatives, and negative life events. HBsAg(+) plus any of the following
      factors, such as poor economic status during the past five years, preferring
      intake of pickled vegetables, history of PHC in their first-degree relatives, and
      negative life events, could increase the risk of PHC.

PMID- 14680601
TI  - [Prevalence of workplace violence in staff of two hospitals in Guangzhou].
AB  - OBJECTIVE: To understand prevalence of workplace violence in hospital and to
      analyse its relevant causes to lay a basis for maintaining normal working order
      in hospital. METHODS: A study was conducted to look into workplace violence
      situation in health care workers in two large hospitals of Guangzhou, Guangdong
      Province during October 2001 to October 2002. Workplace violence was defined as
      any events occurred in hospital staff, who suffered psychological or/and physical
      violence during the past 12 months. RESULTS: Totally, 678 of 1 043 hospital staff
      (65%) investigated had such experience during the past year, mainly psychological
      violence. Medical doctors were more vulnerable than nurses, with prevalence of
      70.3% and 67.7% for medical doctors and nurses, respectively. Prevalence was the
      highest in those aged 30 - 39 years with 11 - 20 years of employment. Man staff
      were more vulnerable to physical violence than women, with prevalence of 11.7%
      and 5.3%, respectively. No significant difference in psychological or sexual
      violence between man and woman staff was found. Frequently, nurses and nurse
      aides were victims of sexual violence. Usually, troublemakers were patients
      relatives or patients themselves, accounting for 64.2% and 50.0% of the total
      events, respectively. Main causes for workplace violence in hospital included
      unreasonable requirement from patients or their relatives which was not met, or
      not-so-quick recovery as they desired. CONCLUSIONS: Workplace violence occurred
      in hospital staff was prevalent in Guangzhou, which should be attached more
      importance. Comprehensive intervention measures should be adopted focusing on law
      reinforcement and education, to maintain normal working order in hospital.

PMID- 14680602
TI  - [An epidemiologic study of diabetes mellitus in employees of Baotou Iron & Steel
      Company].
AB  - OBJECTIVE: To investigate prevalence of diabetes mellitus (DM), impaired glucose
      tolerance (IGT), impaired fasting glucose (IFG) in Baotou Iron & Steel Company
      and to provide scientific evidence for prevention and intervention of DM.
      METHODS: Prevalence of DM was studied in 20 221 workers aged 20 years and over
      (male 15 124 and female 5 097), with the criteria set by the American Diabetes
      Association (ADA, 1997), in Baotou Iron & Steel Company. RESULTS: Prevalence of
      DM, IGT and IFG was 3.22%, 3.48% and 2.09%, respectively in 20 221 subjects,
      adjusted for age, which increased with age, body mass index and waist to hip
      ratio, and 56.30% of them were newly-diagnosed. Family history of DM and
      overweight correlated to prevalence of DM, IGT and IFG, which was higher in
      mental workers than that in physical laborers. The lower level of education, the
      higher prevalence of DM, IGT and IFG. Prevalence of DM, IGT and IFG in the
      workers working under high-temperature condition had no significantly difference
      with that in the control group. Mean blood pressure was significantly higher in
      persons with DM, IGT and IFG than that in the normal controls. CONCLUSIONS: Age,
      overweight, obesity, family history of DM, mental work, low level of education,
      and history of gestation with a huge fetus all were risk factors for DM, IGT and
      IFG. There is no significant impact of high temperature environment on prevalence
      of DM, IGT and IFG.

PMID- 14680603
TI  - [Relationship between mutation of exon G894 T of endothelial nitric oxide
      synthase gene and overweight to essential hypertension].
AB  - OBJECTIVE: To explore the relationship between the 7th exon G894T mutation of
      endothelial nitric oxide synthase (eNOS) gene and overweight in patients with
      essential hypertension. METHODS: Totally, 116 patients with essential
      hypertension taking no medications and 136 normotensives were selected from a
      steel workers as study subjects. Polymerase chain reaction and restriction
      fragment length polymorphism were performed to detect mutation of the 7th exon
      G894T. Additive model was used to analyze interaction between G894T mutation and
      overweight on hypertension. Population attributable risk percent (PAR%) for them,
      etiologic fraction, was applied to their contribution to hypertension. RESULTS:
      There was a positive interaction between G894T mutation and overweight on
      essential hypertension, with an index of interaction of 1.99 and attributable
      interaction percent of 30.76%. Their pure attributable interaction percent was
      36.38%. Multiple logistic regression analysis showed that there still was
      positive interaction between G894T mutation and overweight on essential
      hypertension, adjusted for age, sex, smoking and alcohol drinking. Index of their
      attributable interaction was 2.85, with attributable interaction percent of
      39.97%, also adjusted for the above-mentioned factors. Their pure attributable
      interaction percent was 46.49% and PAR% was estimated as about 15% under certain
      condition. CONCLUSIONS: Interaction between mutation of the 7th exon G894T of
      eNOS gene and overweight played an important role in essential hypertension of
      the studied population. Control of body weight in the population with both G894T
      mutation and overweight could markedly decrease their risk of hypertension.

PMID- 14680604
TI  - [Meta-analysis for relationship between apoE gene polymorphism and coronary heart
      disease].
AB  - OBJECTIVE: To evaluate relationship between ApoE gene polymorphism and coronary
      heart disease (CHD). METHODS: Meta-analysis was applied with a random-effect
      model for the collected data. RESULTS: Difference in pooled frequencies, d, of
      apoE genotypes E3/2, E4/2, E3/3, E4/3 and E4/4 between case and control groups
      were 2.3%, -0.8%, -8.5%, 10.5% and 0.9%, respectively. Difference in pooled
      frequencies, d, of apoE alleles epsilon2, epsilon3 and epsilon4 were -1.5%, -4.2%
      and 5.8%, respectively, with a statistical significance between four groups.
      CONCLUSIONS: apoE gene polymorphism was involved in coronary heart disease.
      Persons with apoE E3/3 genotype or epsilon3 allele were not susceptible to CHD,
      but those with apoE E4/4 genotype or epsilon4 allele had higher risk suffering
      from CHD than others.

PMID- 14680605
TI  - [Study on diagnostic criterion of pregnancy induced hypertension].
AB  - OBJECTIVE: To study the rationality of the current diagnostic criterion of
      pregnancy induced hypertension (PIH) in mainland China. METHODS: To analytically
      review the 916 cases of PIH in our hospital, reclassify them using both the
      current domestic diagnostic criteria and the William Obstetrics' criteria, then
      compare and analyze perinatal and maternal outcomes from the two standards.
      RESULTS: (1) Maternal outcomes: comparison result of the occurrences among three
      groups of premature birth, postpartum haemorrhage and placental abruption
      according to domestic classification had significant difference (P < 0.05). And
      it's the same result according to foreign classification (P < 0.05). But the
      occurrences within three groups of premature birth, postpartum haemorrhage and
      placental abruption between domestic and foreign classifications showed no
      significant difference (P > 0.05). (2) Perinatal outcomes: Comparison results of
      the occurrences among three groups of fetal growth restriction, asphyxia
      neonatorum and perinatal fetal and neonatal death incidence according to domestic
      classification had significant difference (P < 0.05). And it's the same result
      according to foreign classification (P < 0.05). But the occurrences within three
      groups of fetal growth restriction, asphyxia neonatorum and perinatal fetal death
      and neonatal incidence showed no significant difference (P > 0.05). (3) The
      constituent ratio of mild, moderate, severe PIH according to domestic
      classifications was 46.6%, 18.4%, 34.9% respectively. The constituent ratio of
      gestationgal hypertision, mild preeclampsia and severe preeclampsia according to
      foreign classifications was 47.6%, 14.3%, 38.1%. There were significant
      differences between domestic and foreign constituent ratio (P < 0.05). If you
      compare the results from these two diagnostic classifications, with mild PIH, the
      accordant rate was 85.0%; with severe PIH, the rate was 93.8%; but it's only
      40.2% with moderate PIH. CONCLUSIONS: The diagnostic criteria for PIH being used
      in our mainland China is rational, but in the current stage, due to the lack of
      objective index for early diagnosis and overall assessment of patient's
      condition, it's also limited. More objective index should be adopted to improve
      the diagnostic standard for PIH.

PMID- 14680606
TI  - [Expression and tissue localization of hemeoxygenase in human placenta].
AB  - OBJECTIVE: The purpose of this study was to investigate the expression and
      localization of the two known isoforms of hemeoxygenase (HO) in normal human
      first trimester placenta and third trimester placenta. METHODS: Reverse
      transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were
      resorted to demonstrate the expression and localization of HO-1 and HO-2 in
      normal placenta tissue, obtained from 6 approximately 10 week gestation women (20
      cases) and the third trimester woman (20 cases). RESULTS: Compared with
      glyceraldehydes-3-phosphate dehydrogenase (GAPDH), the expression of HO-1 was
      lower, there was no significant difference between the first trimester (0.31 +/-
      0.19) and third trimester (0.28 +/- 0.14) (P > 0.05); the expression of HO-2 was
      higher, it is significantly higher at third trimester (1.12 +/- 0.58) compared
      with first trimester placenta (0.70 +/- 0.48) (P < 0.05). The result of
      immunohistochemistry demonstrated that HO-1 was predominantly localized in
      villous stroma cell and trophoblast; HO-2 predominantly localized in trophoblast
      as well as capillaries, with weak staining of villous stroma. The staining score
      were not normally distributed. The median staining scorse of HO-1 in trophoblast,
      villous stroma and capillaries at first trimester were 9.0, 2.6 and 2.8,
      respectively, at third trimester were 8.7, 2.0 and 1.4, there was no difference
      between the two groups (P > 0.05). The median staining score of HO-2 in
      capillaries at first trimester was 5.8, significantly lower than that of the
      third trimester (9.3) (P < 0.05). There was no significant difference between the
      staining score of HO-2 in trophoblast (10.5, 8.0) and villous stroma (3.6, 2.4)
      between the first trimester and the third trimester (P > 0.05). CONCLUSIONS: HO-1
      and HO-2 as endogenous system may regulate feto-placental circulation, indicated
      their different roles in placental vascular development and regulation. They may
      offer protection against cyto-toxic damage in the placenta, and influence
      immunological function.

PMID- 14680607
TI  - [Thyroid functional changes of normal human fetus and newborns].
AB  - OBJECTIVE: To study the changes of the thyroid hormones level of human fetus and
      newborns. METHODS: More than 71 cases of medically indicated cordocentesis have
      been done in 16 -36 gestational weeks in our hospital during last three years.
      Among them, 71 fetus who were free of diseases and their maternal thyroid
      function were normal were included into the study group. The blood samples were
      sent to analysis of thyroxine (T(4)), triiodothyroxine (T(3)), free thyroxine
      (FT(4)), free triiodothyroxine (FT(3)) and thyrotropin (TSH). 140 umbilical cord
      blood samples taken at the time of term delivery were sent to analysis of FT(4),
      FT(3) and TSH as a control. Normal range of different gestational weeks was
      calculated. Statistical analysis was done for the changes of all these thyroid
      hormones before 28 weeks and after. RESULTS: All the thyroid hormones can be
      detected in 16 weeks of pregnancy, FT(4) already reaches the top level of adults
      (5.8 +/- 2.6) pmol/L and will continually increase with the increase of
      gestational age. There was a parallel increment of all the fetal thyroid hormone
      concentrations with the gestational age. The concentrations of T(4), T(3) and
      FT(4) have a rapidly increase after 28 weeks and have a statistically significant
      difference from (2.8 +/- 1.8) nmol/L, (37.2 +/- 27.2) nmol/L and (10.6 +/- 3.1)
      pmol/L, respectively to (5.8 +/- 2.6) nmol/L, (55.9 +/- 33.3) nmol/L, (13.0 +/-
      4.5) pmol/L, respectively. TSH level of fetus was increased gradually along the
      gestation, reaching the up level of the adults at the 20 weeks and peaking at the
      birth time. While the T(3) and FT(3) keep in a lower level in gestation.
      CONCLUSIONS: Fetal thyroid hormones increase with the gestational age. The
      diagnosis of congenital fetal thyroid hormone malfunction in the second half of
      the pregnancy should be monitored mainly by the T(4), FT(4) and TSH levels in
      different gestational age. For this consideration, to set up a reliable data for
      normal human fetus thyroid hormone concentrations is a very important and
      essential step to provide a practical guide for doctors to do intra-uterine
      diagnosis and treatment of associated high-risk groups. The peaking level of TSH
      at the birth time will surely company the changing of other thyroid hormones, so
      it might not be the best time to screening the congenital thyroid malfunction at
      the 72 hours after birth.

PMID- 14680608
TI  - [Regulation of epidermal growth factor, thyrotropin releasing hormone and
      dexamethasone on the expression of fetal lung SP mRNAs in rabbits].
AB  - OBJECTIVE: To compare the effect of epidermal growth factor (EGF), thyrotropin
      releasing hormone (TRH) and dexamethasone (Dex) on the expression of surfactant
      protein (SP)-A, SP-B and SP-C mRNA in fetal rabbit lungs. METHODS: Sixty-four
      Japanese white pregnant rabbits, put into four different groups (16 rabbits
      each), were given EGF (EGF group), TRH (TRH group), Dex (Dex group) or normal
      saline (control group) intravenously from gestational day 22(nd) (5 rabbits in
      each group) or 24(th) (11 rabbits in each group) for three days before killing.
      The levels of SP-A, SP-B and SP-C mRNAs in the fetal rabbit lungs were detected
      by reverse transcription polymerase chain reaction (RT-PCR) and Southern
      blotting. RESULTS: In the 27(th) gestational day, SP-B mRNA levels in the fetal
      rabbit lungs in all treated groups were found significantly higher than those in
      the control group (P < 0.05). In the 25(th) day, there had a higher expression of
      SP-A and SP-C mRNAs in the fetal lungs in all groups, but SP-B mRNA could be
      tested only in the Dex group. SP-B mRNA level was lower than that of SP-A mRNA
      and SP-C mRNA in the same fetal lungs in the 27(th) gestationed day. CONCLUSION:
      The time of detectable SP-B mRNA in rabbit fetal lungs appeared later than that
      of the SP-A and SP-C mRNAs. The expression of SP-B mRNA is lower in comparison
      with those of SP-A mRNA and SP-C mRNA in the same samples. Prenatal maternal
      treatment with intravenously Dex, EGF and TRH could increase the expression of SP
      B mRNA in fetal rabbit lungs, and the effect of Dex may be more significant at
      earlier stage of gestation.

PMID- 14680609
TI  - [Effects of metformin on gonadotropin-induced ovulation in patients with
      polycystic ovary syndrome].
AB  - OBJECTIVE: To evaluate the effects of metformin on gonadotropin-induced ovulation
      in patients with polycystic ovary syndrome (PCOS). METHODS: Forty patients with
      PCOS (study group) and 20 women with normal weight and menstrual cycle (control
      group) were enrolled. Serum follicle stimulating hormone (FSH), luteinizing
      hormone (LH), testosterone (T), fasting glucose (FG), fasting insulin (FINS) and
      fasting leptin were measured before and after treatment. In the study group, 20
      cases (group A) were assigned to take 500 mg of metformin three times daily for
      12 weeks, if pregnancy did not occur, high purified FSH (FSH-HP) was added for
      one cycle; another 20 cases (group B) were induced ovulation with FSH-HP alone
      for one cycle. RESULTS: There were significant high FINS and leptin levels in the
      study group as compared with the control group [(20 +/- 16) vs (12 +/- 6) nmol/L,
      P < 0.05; (14 +/- 16) vs (8 +/- 4) mg/L, P < 0.05]. The obese PCOS group had
      markedly higher serum FINS and leptin than the non-obese PCOS group [(24 +/- 18)
      vs (14 +/- 8) nmol/L, P < 0.05; (20 +/- 22) vs (8 +/- 4) mg/L, P < 0.05], but
      serum FINS and FG were not significantly different between the non-obese PCOS and
      the control group (P > 0.05). After administration of metformin for 12 weeks,
      serum LH, T, leptin and FINS decreased significantly (P < 0.05 - 0.01), serum FSH
      levels and body mass index showed a slight decrease, whereas no change was found
      in FG. In the study group, 3 cases conceived during metformin therapy, the
      remaining 37 were induced ovulation with FSH-HP or FSH-HP and metformin, 7 cases
      obtained pregnancy. The rates of ovulation and pregnancy in group A were higher
      than those in group B (88% vs 70%, 24% vs 15%), but no significant difference was
      found. CONCLUSIONS: Metformin therapy in PCOS can decrease the FINS and leptin
      levels, normalize the endocrine abnormalities, resumes ovulation and pregnancy in
      some patients, and may improve the ovarian response to gonadotropin.

PMID- 14680610
TI  - [Effect of estradiol and progesterone on production of macrophage colony
      stimulating factor by human granulosa cells in vitro].
AB  - OBJECTIVE: To investigate the effect of estradiol (E(2)) and progesterone (P) on
      macrophage colony-stimulating factor (M-CSF) production by human luteinized
      granulosa cells in vitro. METHODS: Human luteinized granulosa cells were isolated
      from follicular fluid of superovulated infertile patients undergoing
      intracytoplasmatic sperm injection (ICSI). Luteinized granulosa cells were
      cultured with HAM's F-10 medium with various concentrations of E(2) or P (0, 1 x
      10(-7), 1 x 10(-6), 1 x 10(-5), 1 x 10(-4), 1 x 10(-3) mol/L). Media were removed
      at 72 h after culture. M-CSF in media was measured by a solid phase enzyme-linked
      immunosorbant assay (ELISA) and estradiol and progesterone in media were measured
      by enzyme immunoassays (EIA). RESULTS: The basic concentration of M-CSF in
      cultivated granulosa cells without E(2) stimulation was low (47 +/- 15 ng/L).
      However, E(2) at concentrations of 1 x 10(-6) - 1 x 10(-3) mol/L caused a
      significant increase of M-CSF secretion by luteinized granulosa cells in a dose
      dependent mode (2.3, 4.5, 6.9, 7.9 times higher than the basic level,
      respectively) (P < 0.05). E(2) at a concentration of 1 x 10(-7) mol/L, however,
      did not stimulate the production of M-CSF (P > 0.05). P at concentrations of 1 x
      10(-7) - 1 x 10(-3) mol/L showed no effect on M-CSF production by luteinized
      granulosa cells (P > 0.05). CONCLUSIONS: Estradiol can stimulate M-CSF production
      by luteinized granulosa cells in vitro in a dose-dependent mode, on the other
      hand P cannot induce M-CSF production by luteinized granulosa cells. The
      mechanism of estradiol regulating follicular development may partially via M
      CSF/receptor pathway.

PMID- 14680611
TI  - [Study on the treatment of high dose mifepristone and progesterone in endometrial
      carcinoma].
AB  - OBJECTIVE: To investigate the effect of high dose mifepristone and high dose
      progesterone in the treatment of patients with endometrial carcinoma and to
      explore the possible mechanisms associating with them. METHODS: Thirty untreated
      patients diagnosed as endometrial carcinoma through dilation and curettage of the
      uteri were divided into 3 groups at random. Each group was given
      medroxyprogesterone acetate (MPA), (500 mg/day) or mifepristone (MIF), (100
      mg/day) or MIF (100 mg/day) + MPA (500 mg/day) for 5 days respectively. On the
      sixth day, hysterectomy was performed on these patients. The endometrial cancer
      specimen of post-hysterectomy was compared with the one of pre-administrating.
      The morphologic changes of the endometrial cancer cells were observed through
      light microscope. Immunohistochemistry assay (SP method) was applied to determine
      the localization and immunoreactive intensity of proliferating cell nuclear
      antigen (PCNA), estrogen receptor (ER), progesterone receptor (PR), B-cell
      leukemia lymphoma-2 (bcl-2), bcl-2 associated X protein (bax) and CD(44v6).
      RESULTS: Better differentiation degree and active excretion were observed in all
      of the post-hysterectomy endometrial specimen. In the same time, apoptosis of
      carcinoma cells was observed. The most significant changes were seen in the MIF +
      MPA group. In the MPA group, the pre-treatment and post-treatment expression of
      PR (2.9 +/- 1.1, 1.6 +/- 0.8), ER (2.8 +/- 0.9, 1.4 +/- 0.9), PCNA (0.84 +/-
      0.10, 0.60 +/- 0.12), bcl-2 (0.236 +/- 0.089, 0.157 +/- 0.981) and CD(44v6) (4.6
      +/- 1.8, 2.5 +/- 1.9) were all decreased (all P < 0.01); the expression of bax
      (0.20 +/- 0.10, 0.42 +/- 0.07) was increased (P < 0.01). In the MIF group, the
      expression of PR (3.4 +/- 1.0, 1.9 +/- 0.8), ER (2.7 +/- 0.9, 1.2 +/- 0.7), PCNA
      (0.80 +/- 0.15, 0.65 +/- 0.10), bcl-2 (0.214 +/- 0.097, 0.121 +/- 0.073) were all
      decreased (all P < 0.01); the expression of bax (0.21 +/- 0.05, 0.44 +/- 0.09)
      was increased (P < 0.01); no significant change in the expression of CD(44v6)
      (4.2 +/- 2.0, 4.3 +/- 1.7) was seen (P > 0.05). In the MIF + MPA group, the
      expression of PR (3.2 +/- 1.0, 0.8 +/- 0.8), ER (2.7 +/- 0.9, 0.7 +/- 0.9), PCNA
      (0.81 +/- 0.09, 0.25 +/- 0.09), bcl-2 (0.225 +/- 0.091, 0.066 +/- 0.009) and
      CD(44v6) (4.5 +/- 1.9, 2.7 +/- 1.6) were all decreased (all P < 0.01); the
      expression of bax (0.22 +/- 0.06, 0.59 +/- 0.09) was increased (P < 0.01); there
      were significant different expression of PCNA, ER, PR, bax and bcl-2 as compared
      with the MIF group and the MPA group, respectively (all P < 0.01). The expression
      of CD(44v6) was significantly different (P < 0.01) between the MIF + MPA group,
      and the MIF group, but not significantly different between the MIF + MPA group
      and the MPA group. CONCLUSIONS: The study indicates that high dose progesterone
      could inhibit the growth, promote apoptosis and inhibit metastasis of endometrial
      carcinoma, MIF could inhibit the growth and promote apoptosis, MIF + MPA could
      more strongly inhibit the growth, promote apoptosis and inhibit metastasis of
      endometrial carcinoma than MIF or MPA, and synergistic effect was observed on the
      expression of PCNA, ER, PR, bax and bcl-2.

PMID- 14680612
TI  - [Study of ceramide monohexoside in ovarian cell line COC1/DDP resistant to
      cisplantin].
AB  - OBJECTIVE: To investigate the effect of ceramide monohexoside (CMH) on resistance
      to cisplatin and apoptosis in ovarian cell line COC1/DDP, and to provide new
      ideals and clues to seek new effective methods for studying the mechanism and
      reversing the resistance in ovarian cell line as well. METHODS: COC1 cells and
      COC1/DDP cells (before and after the treatment of mifepristone) were collected
      and neutral glycosphingolipids (N-GSLs) of the cells was isolated and purified,
      changes of CMH content were analyzed by high performance thin layer
      chromatography (HPTLC). The COC1/DDP cells were divided into three groups, one
      treated by cisplatin, one treated by mifepristone, the other treated by cisplatin
      and mifepristone. The survival rate of cells in three groups were evaluated by
      the methyl thiazolyl tetrazolium (MTT) assay, DNA ladders were presented by DNA
      gel electrophoresis, the forms of cells were observed by transmission electron
      microscope (TEM). RESULTS: The levels of CMH were (37.1 +/- 3.3)% in COC1/DDP,
      higher than that in COC1 (14.1 +/- 1.4)% (P < 0.001). After treating by 1.25, 5
      micro mol/L mifepristone, the CMH were (26.6 +/- 2.6)% (P < 0.05) and (17.5 +/-
      0.7)% (P < 0.001), respectively. Mifepristone had no effect on the viability of
      COC1/DDP cell below a concentration of 5 micro mol/L. But when mifepristone of
      1.25 or 5 micro mol/L combined with cisplatin at a concentration of 0.1, 0.25,
      0.5, 1.25, 2.5 micro g/ml, the inhibition rate of COC1/DDP cell is higher than
      that of COC1/DDP cells only treated by cisplatin at the concentration of 0.1 to
      2.5 micro g/ml (P < 0.001). The combined treatment elicited DNA fragmentation,
      however, neither cisplatin of 1.25 micro g/ml nor mifepristone of 5 micro mol/L
      alone could potentiate DNA fragmentation. After the combined treatment, the
      COC1/DDP cells produced apoptosis body. CONCLUSIONS: CMH is related with
      resistance to cisplantin in ovarian cell line COC1/DDP. When CMH of COC1/DDP
      cells was inhibited by mifepristone, the cells were sensitive to cisplatin and
      apoptosis was elicited.

PMID- 14680613
TI  - [Experimental study on apoptosis in T cells induced by ovarian carcinoma cells].
AB  - OBJECTIVE: To investigate apoptosis in T cells induced by ovarian carcinoma cells
      and analyze the role of nitric oxide and intracellular free calcium in this
      process. METHODS: Apoptosis induced by ovarian carcinoma cell lines supernatants
      was investigated by electron microscopy and flow cytometry. Reverse transcription
      polymerase chain reaction (RT-PCR) was used to detect the expression of inducible
      nitric oxide synthase (iNOS) mRNA. Calcium ions ([Ca(2+)]i) and cycle guanosine
      monophosphate (cGMP) were determined by Fura-2 fluorescein load technique and
      enzyme immunoassay (EIA), respectively. RESULTS: Cluster of differentiation
      (CD)8(+) T cells cocultured with ovarian carcinoma cell lines supernatants
      expressed typical change of apoptosis, such as condensation and fragmentation of
      chromosomes, apoptosis peak in flow cytometry and higher apoptotic ratios[(23.8
      +/- 3.5)%, (23.1 +/- 2.9)%, (24.2 +/- 4.9)% vs (4.6 +/- 0.5)%, P < 0.01]. The
      expression of iNOS mRNA and cGMP level in the process of CD(8)(+) T cellular
      apoptosis were significantly enhanced as compared to that of control group [1.14
      +/- 0.03, 1.05 +/- 0.04, 1.16 +/- 0.02 vs 0.60 +/- 0.03, P < 0.01; (0.65 +/-
      0.09), (0.62 +/- 0.16), (0.57 +/- 0.12) pmol/Lvs (0.29 +/- 0.04) pmol/ml, P <
      0.01], and [Ca(2+)]i was significantly higher [(380 +/- 38), (366 +/- 13), (356
      +/- 20) nmol/L vs (184 +/- 11) nmol/L, P < 0.01]. CONCLUSION: Nitric oxide and
      intracellular free calcium may play a key role in apoptotic T cell induced by
      ovarian carcinoma.

PMID- 14680614
TI  - [Luteal phase treatment with mifepristone and misoprostol for prevention of
      pregnancy].
AB  - OBJECTIVE: To assess the efficacy and side-effects after treatment of 100 mg
      mifepristone and misoprostol in the luteal phase of the cycle. METHODS: This
      study was carried out in seven family planning clinics in China, including 699
      women who were exposed to unprotected intercourse more than five days earlier or
      having had more than one episode of unprotected intercourse in the same cycle.
      Mifepristone 100 mg was given on admission followed two days later by 400 micro g
      misoprostol orally in the luteal phase of the cycle. RESULTS: One woman was lost
      to follow-up after taking mifepristone. After treatment 25 women (3.6%) were
      pregnant and 673 women had return of menstruation, among whom, 381 (56.6%) had
      the return of menstruation +/- 3 days of the expected day, 57 women (8.5%) had a
      delay of menstruation > 7 days. Pregnancy rate was related to the number of acts
      of intercourse before treatment, the difference was statistically significant (P
      < 0.05). The main side effects within a week after treatment were diarrhoea and
      abdominal pain (31.1%) as well as nausea and vomiting (20.4%). CONCLUSION: The
      use of mifepristone with misoprostol during luteal phase provides an option for
      occasional use for preventing pregnancy.

PMID- 14680615
TI  - Adverse reactions to neuromuscular blocking agents.
AB  - Neuromuscular blocking agents (NMBAs) play a predominant role in the incidence of
      severe adverse reactions occurring during anesthesia. Most hypersensitivity
      reactions are of immunologic origin (IgE-mediated) or are related to direct
      stimulation of histamine release. The incidence of IgE-mediated hypersensitivity
      or anaphylaxis is estimated between 1 in 10,000 and 1 in 20,000 anesthesias, and
      NMBAs represent the most frequently involved substances, with a range of 50% to
      70%. Any suspected anaphylactic reaction must be extensively investigated using
      combined perioperative and postoperative testing. Because of the frequent cross
      reactivity observed with muscle relaxants, every available NMBA should be tested.
      This should help provide documented advice for future administration of
      anesthesia. There is no demonstrated evidence for systematic preoperative
      screening in the general population at this time. Other well-known adverse
      effects have been described, such as the succinylcholine-triggered cytotoxic
      effects on muscle cells, but these are responsible for characteristic clinical
      symptoms, which are usually easy to distinguish from anaphylactic reactions

PMID- 14680616
TI  - Adverse respiratory reactions to aspirin and nonsteroidal anti-inflammatory
      drugs.
AB  - Aspirin-exacerbated respiratory disease (AERD) is an adult-onset condition that
      manifests as asthma, rhinosinusitis/nasal polyps, and sensitivity to aspirin and
      other cyclooxygenase-1 (COX-1)-inhibitor nonsteroidal anti-inflammatory drugs
      (NSAIDs). There is no cross-sensitivity to highly selective COX-2 inhibitors.
      AERD is chronic and does not improve with avoidance of COX-1 inhibitors. The
      diagnosis of AERD is made through provocative challenge testing. Following a
      positive aspirin challenge, patients can be desensitized to aspirin and NSAIDs.
      The desensitized state can be maintained indefinitely with continued daily
      administration. After desensitization, there is an approximately 48-hour
      refractory period to adverse effects from aspirin. The pathogenesis of AERD
      remains unknown, but these patients have been shown to have multiple
      abnormalities in arachidonic acid metabolism and in cysteinyl leukotriene 1
      receptors. AERD patients can take up to 650 mg of acetaminophen for analgesic or
      antipyretic relief. Patients can also use weak COX-1 inhibitors, such as sodium
      salicylate or choline magnesium trisalicylate. Treatment of AERD patients with
      antileukotriene medications has been helpful but not preferential when compared
      with non-AERD patients. An alternative treatment for many AERD patients is
      aspirin desensitization. This is particularly effective in reducing upper-airway
      mucosal congestion, nasal polyp formation, and systemic steroids.

PMID- 14680617
TI  - Hypersensitivity reactions to radiocontrast media: the role of complement
      activation.
AB  - Although intravenous use of radiocontrast media (RCM) for a variety of
      radiographic procedures is generally safe, clinically significant acute
      hypersensitivity reactions still occur in a significant percentage of patients.
      The mechanism of these anaphylactoid, or "pseudoallergic," reactions is complex,
      involving complement activation, direct degranulation of mast cells and
      basophils, and modulation of enzymes and proteolytic cascades in plasma. In this
      review, basic information on different RCMs and their reactogenicity is
      summarized and updated, and the prevalence, pathomechanism, prediction,
      prevention, treatment, and economic impact of hypersensitivity reactions are
      discussed. Particular attention is paid to the in vitro and in vivo evidence
      supporting complement activation as an underlying cause of RCM reactions.

PMID- 14680620
TI  - Preventing food allergy.
AB  - In this review, we examine the critical periods of immune development and how
      these might be modified to prevent food allergy. The relevant dietary
      intervention studies, roles of microorganisms and their products, and other
      strategies are critically analyzed. Additionally, we highlight the potential
      importance of different routes of allergic sensitization and the role of oral
      tolerance induction in the pathogenesis and prevention of food allergy.

PMID- 14680621
TI  - What makes a food protein an allergen?
AB  - Food allergens are almost always proteins, but not all food proteins are
      allergens. This one statement sums up the purpose of this article, defining the
      difference between an innocuous food protein and a food allergen. The simplest
      answer is that a food allergen has the ability to first elicit an IgE response,
      and then, on subsequent exposures, to elicit a clinical response to the same or
      similar protein. However, this simplistic answer avoids the more complex issues
      of defining the biochemical characteristics that allow a food protein to survive
      the extremes of food processing, escape the digestive enzymes of the human
      gastrointestinal tract, and interact with the immune system. More than 700
      allergen sequences have been identified from food and nonfood sources. However,
      despite increasing knowledge of the structure and amino acid sequences of the
      identified allergens, only a few biochemical characteristics can be associated
      with food allergens. Food allergen characteristics, including abundance of the
      protein in the food; multiple, linear IgE binding epitopes; resistance of the
      protein to digestion and processing; and allergen structure are discussed, and
      the possible reasons they predispose some food proteins to become allergens are
      suggested.

PMID- 14680622
TI  - The role of mast cells in common gastrointestinal diseases.
AB  - The gastrointestinal tract is a rich source of mast cells with an enormous
      surface area that permits a high degree of interaction between the mast cell and
      the intestinal contents. The active metabolic products of the mast cell influence
      gastrointestinal secretion, absorption, and motility through paracrine effects of
      local mast cell activation and also cause systemic effects through the release of
      cellular products into the bloodstream. Recent advances in our knowledge of the
      immune system and the recognition that the gastrointestinal immune function might
      be partially mediated through gastrointestinal mucosal mast cells has opened mast
      cell research to the field of gastroenterology. Local gastrointestinal
      proliferation of mast cells in response to recognized or obscure stimuli can
      alter gastrointestinal function and induce systemic symptoms. Symptoms can arise
      from the increased number of mast cells, overproduction of specific mast cell
      mediators, and hyperactivity of the enteric nervous system that induces mast cell
      activation. The diseases mentioned in this review represent a small proportion of
      areas where mast cell function might play an important role in the response to
      disease and generation of symptoms.

PMID- 14680623
TI  - Food allergy and the food industry.
AB  - Although most food-allergic reactions occur after ingestion of nonpackaged food
      products, the food industry has been subjected to increasing scrutiny of their
      allergen controls; the resulting impact on the industry has been remarkable.
      Undeclared food allergens have been responsible for many food product recalls
      during the past 13 years, and the food industry has made significant investment,
      effort, and improvements in allergen control during this time. Recently, tests
      for some allergenic foods have been commercialized, and proven useful to the
      industry in controlling allergens and helpful for regulatory agencies
      investigating food-allergic consumer complaints. However, testing methods still
      do not exist for some of the common allergenic foods. Labeling initiatives have
      been pursued to make ingredient listings more easily understood by food-allergic
      consumers, but further improvements could still be made. Additional research to
      determine eliciting doses for allergenic foods is needed to enable science-based
      risk assessment and risk management.

PMID- 14680625
TI  - Analysis of leukocyte extravasation across the blood-brain barrier: conceptual
      and technical aspects.
AB  - The central nervous system (CNS) has long been described as an immunologically
      privileged organ. However, evidence is accumulating that the CNS is more
      adequately described as immune competent, albeit atypical. Leukocyte trafficking
      into the CNS in response to inflammation, as in peripheral organs, occurs in
      several distinct steps. As with all leukocyte trafficking, the overall process is
      governed in part by chemokines. The CNS has unique anatomic and physiologic
      attributes, including the blood-brain barrier. These characteristic features of
      the CNS interact with a distinct array of chemokines, expressed both
      constitutively and in response to inflammation. In this review, we consider the
      potential sites of chemokine action in guiding leukocyte migration. The process
      of extravasation can usefully be regarded as comprising individual steps. This
      review is focused on the need to consider these stages separately, and the
      elucidation of mechanisms at each stage is outlined.

PMID- 14680626
TI  - Chemokines in eosinophil-associated gastrointestinal disorders.
AB  - Eosinophil-associated gastrointestinal disorders (EGDs) are characterized by a
      pronounced cellular inflammation. Recent clinical and experimental investigations
      have implicated a family of molecules known as chemokines in the regulation of
      leukocyte recruitment in these diseases. The underlying cellular and molecular
      mechanisms involved in chemokine-mediated cellular infiltration are largely
      unknown. In this review, we describe the role of CD4+ T cells and eosinophils in
      the clinical manifestations of EGDs and discuss the current understanding of the
      role of chemokines in the recruitment of these cells in the expression of
      diseases.

PMID- 14680628
TI  - Shroom induces apical constriction and is required for hingepoint formation
      during neural tube closure.
AB  - BACKGROUND: The morphogenetic events of early vertebrate development generally
      involve the combined actions of several populations of cells, each engaged in a
      distinct behavior. Neural tube closure, for instance, involves apicobasal cell
      heightening, apical constriction at hingepoints, convergent extension of the
      midline, and pushing by the epidermis. Although a large number of genes are known
      to be required for neural tube closure, in only a very few cases has the affected
      cell behavior been identified. For example, neural tube closure requires the
      actin binding protein Shroom, but the cellular basis of Shroom function and how
      it influences neural tube closure remain to be elucidated. RESULTS: We show here
      that expression of Shroom is sufficient to organize apical constriction in
      transcriptionally quiescent, naive epithelial cells but not in non-polarized
      cells. Shroom-induced apical constriction was associated with enrichment of
      apically localized actin filaments and required the small GTPase Rap1 but not
      Rho. Endogenous Xenopus shroom was found to be expressed in cells engaged in
      apical constriction. Consistent with a role for Shroom in organizing apical
      constriction, disrupting Shroom function resulted in a specific failure of
      hingepoint formation, defective neuroepithelial sheet-bending, and failure of
      neural tube closure. CONCLUSIONS: These data demonstrate that Shroom is an
      essential regulator of apical constriction during neurulation. The finding that a
      single protein can initiate this process in epithelial cells establishes that
      bending of epithelial sheets may be patterned during development by the
      regulation of expression of single genes.

PMID- 14680627
TI  - Chemokines in inflammatory bowel disease.
AB  - Ulcerative colitis (UC) and Crohn's disease (CD), collectively termed
      inflammatory bowel diseases (IBD), represent chronic relapsing and remitting
      inflammatory disorders of the gastrointestinal tract that are characterized by
      leukocytic infiltration of the intestinal mucosa and submucosa. In CD, the
      inflammation is transmural and frequently associated with granuloma formation.
      Chemokines have emerged as the most important regulators of leukocyte trafficking
      during infection or inflammation and, therefore, have been implicated in the
      pathogenesis of IBD. In this review, recent advances on the role of chemokines
      and their receptors in mucosal immunity and inflammation are discussed, and the
      potential use of chemokine/chemokine-receptor antagonists as novel therapeutic
      targets for the treatment of human IBD is highlighted.

PMID- 14680629
TI  - heart of glass regulates the concentric growth of the heart in zebrafish.
AB  - BACKGROUND: Patterned growth of vertebrate organs is essential for normal
      physiological function, but the underlying pathways that govern organotypic
      growth are not clearly understood. Heart function is critically dependent upon
      the concentric thickening of the ventricular wall generated by the addition of
      cells to the myocardium along the axis from the endocardium (inside) to the
      outside of the chamber. In heart of glass mutant embryos, the number of cells in
      the myocardium is normal, but they are not added in the concentric direction. As
      a consequence, the chambers are huge and dysfunctional, and the myocardium
      remains a single layer. RESULTS: To begin to define the factors controlling the
      concentric growth of cells in the myocardium, we used positional cloning to
      identify the heart of glass (heg) gene. heg encodes a protein of previously
      undescribed function, expressed in the endocardial layer of the heart. By
      alternative splicing, three distinct isoforms are generated, one of which is
      predicted to be transmembrane and two other secreted. By selective morpholino
      perturbation, we demonstrate that the transmembrane form is critical for the
      normal pattern of growth. CONCLUSIONS: heart of glass encodes a previously
      uncharacterized endocardial signal that is vital for patterning concentric growth
      of the heart. Growth of the heart requires addition of myocardial cells along the
      endocardial-to-myocardial axis. This axis of patterning is driven by heg, a novel
      transmembrane protein expressed in the endocardium.

PMID- 14680630
TI  - Structure and function of the conserved core of histone deposition protein Asf1.
AB  - BACKGROUND: Asf1 is a ubiquitous eukaryotic histone binding and deposition
      protein that mediates nucleosome formation in vitro and is required for genome
      stability in vivo. Studies in a variety of organisms have defined Asf1's role as
      a histone chaperone during DNA replication through specific interactions with
      histones H3/H4 and the histone deposition factor CAF-I. In addition to its role
      in replication, conserved interactions with proteins involved in chromatin
      silencing, transcription, chromatin remodeling, and DNA repair have also
      established Asf1 as an important component of a number of chromatin assembly and
      modulation complexes. RESULTS: We demonstrate that the highly conserved N
      terminal domain of S. cerevisiae Asf1 (Asf1N) is the core region that mediates
      all tested functions of the full-length protein. The crystal structure of this
      core domain, determined to 1.5 A resolution, reveals a compact immunoglobulin
      like beta sandwich fold topped by three helical linkers. The surface of Asf1
      displays a conserved hydrophobic groove flanked on one side by an area of strong
      electronegative surface potential. These regions represent potential binding
      sites for histones and other interacting proteins. The structural model also
      allowed us to interpret mutagenesis studies of the human Asf1a/HIRA interaction
      and to functionally define the region of Asf1 responsible for Hir1-dependent
      telomeric silencing in budding yeast. CONCLUSIONS: The evolutionarily conserved,
      N-terminal 155 amino acids of histone deposition protein Asf1 are functional in
      vitro and in vivo. This core region of Asf1 adopts a compact immunoglobulin-fold
      structure with distinct surface characteristics, including a Hir protein binding
      region required for gene silencing.

PMID- 14680632
TI  - Evidence of splice signal migration from exon to intron during intron evolution.
AB  - A comparison of the nucleotide sequences around the splice junctions that flank
      old (shared by two or more major lineages of eukaryotes) and new (lineage
      specific) introns in eukaryotic genes reveals substantial differences in the
      distribution of information between introns and exons. Old introns have a lower
      information content in the exon regions adjacent to the splice sites than new
      introns but have a corresponding higher information content in the intron itself.
      This suggests that introns insert into nonrandom (proto-splice) sites but, during
      the evolution of an intron after insertion, the splice signal shifts from the
      flanking exon regions to the ends of the intron itself. Accumulation of
      information inside the intron during evolution suggests that new introns largely
      emerge de novo rather than through propagation and migration of old introns.

PMID- 14680631
TI  - Coordinated regulation of actin filament turnover by a high-molecular-weight
      Srv2/CAP complex, cofilin, profilin, and Aip1.
AB  - BACKGROUND: Dynamic remodeling of the actin cytoskeleton requires rapid turnover
      of actin filaments, which is regulated in part by the actin filament
      severing/depolymerization factor cofilin/ADF. Two factors that cooperate with
      cofilin are Srv2/CAP and Aip1. Human CAP enhances cofilin-mediated actin turnover
      in vitro, but its biophysical properties have not been defined, and there has
      been no in vivo evidence reported for its role in turnover. Xenopus Aip1 forms a
      cofilin-dependent cap at filament barbed ends. It has been unclear how these
      diverse activities are coordinated in vivo. RESULTS: Purified native yeast
      Srv2/CAP forms a high molecular weight structure comprised solely of actin and
      Srv2. The complex is linked to actin filaments via the SH3 domain of Abp1. Srv2
      complex catalytically accelerates cofilin-dependent actin turnover by releasing
      cofilin from ADP-actin monomers and enhances the ability of profilin to stimulate
      nucleotide exchange on ADP-actin. Yeast Aip1 forms a cofilin-dependent filament
      barbed end cap, disrupted by the cof1-19 mutant. Genetic analyses show that
      specific combinations of activities mediated by cofilin, Srv2, Aip1, and capping
      protein are required in vivo. CONCLUSIONS: We define two genetically and
      biochemically separable functions for cofilin in actin turnover. One is formation
      of an Aip1-cofilin cap at filament barbed ends. The other is cofilin-mediated
      severing/depolymerization of filaments, accelerated indirectly by Srv2 complex.
      We show that the Srv2 complex is a large multimeric structure and functions as an
      intermediate in actin monomer processing, converting cofilin bound ADP-actin
      monomers to profilin bound ATP-actin monomers and recycling cofilin for new
      rounds of filament depolymerization.

PMID- 14680633
TI  - PKD2 cation channel is required for directional sperm movement and male
      fertility.
AB  - Sperm of both mammals and invertebrates move toward specific sites in the female
      reproductive tract. However, molecular mechanisms for sperm to follow directional
      cues are unknown. Here, we report genetic analysis of Drosophila Pkd2 at 33E3
      (Pkd2, CG6504), which encodes a Ca(2+)-activated, nonselective cation channel
      homologous to the human Pkd2 autosomal dominant polycystic kidney disease (ADPKD)
      gene. The PKD2 family of genes has been implicated in sensory responses through
      protein localization on primary cilia of epithelia and neurons. In renal tubules,
      cilium-associated PKD2 appears to mediate Ca(2+) influx in response to fluid
      flow, and the loss of fluid sensation probably contributes to cyst growth and
      ADPKD. Sperm tails or flagella are specialized cilia essential for movement.
      Drosophila Pkd2 is abundantly associated with the tail and the acrosome
      containing head region of mature sperm. Targeted disruption of Pkd2 results in
      male sterility without affecting spermatogenesis. The mutant sperm are motile but
      fail to swim into the storage organs in the female. Rare mutant sperm that reach
      the storage organs are able to fertilize the egg and produce viable progeny. Our
      data demonstrate that the Drosophila PKD2 cation channel operates in sperm for
      directional movement inside the female reproductive tract.

PMID- 14680634
TI  - A flagellar polycystin-2 homolog required for male fertility in Drosophila.
AB  - A common inherited cause of renal failure, autosomal dominant polycystic kidney
      disease results from mutations in either of two genes, PKD1 and PKD2, which
      encode polycystin-1 and polycystin-2, respectively. Polycystin-2 has distant
      homology to TRP cation channels and associates directly with polycystin-1. The
      normal functions of polycystins are poorly understood, although recent studies
      indicate that they are concentrated in the primary cilia of a variety of cell
      types. In this report we identified a polycystin-2 homolog in Drosophila
      melanogaster; this homolog localized to the distal tip of the sperm flagella. A
      targeted mutation in this gene, almost there (amo), caused nearly complete male
      sterility. The amo males produced and transferred normal amounts of motile sperm
      to females, but mutant sperm failed to enter the female sperm storage organs, a
      prerequisite for fertilization. The finding that Amo functions in sperm flagella
      supports a common and evolutionarily conserved role for polycystin-2 proteins in
      both motile and nonmotile axonemal-containing structures.

PMID- 14680635
TI  - Keratinocyte differentiation is regulated by the Rho and ROCK signaling pathway.
AB  - The epidermis comprises multiple layers of specialized epithelial cells called
      keratinocytes. As cells are lost from the outermost epidermal layers, they are
      replaced through terminal differentiation, in which keratinocytes of the basal
      layer cease proliferating, migrate upwards, and eventually reach the outermost
      cornified layers. Normal homeostasis of the epidermis requires that the balance
      between proliferation and differentiation be tightly regulated. The GTP binding
      protein RhoA plays a fundamental role in the regulation of the actin cytoskeleton
      and in the adhesion events that are critically important to normal tissue
      homeostasis. Two central mediators of the signals from RhoA are the ROCK
      serine/threonine kinases ROCK-I and ROCK-II. We have analyzed ROCK's role in the
      regulation of epidermal keratinocyte function by using a pharmacological
      inhibitor and expressing conditionally active or inactive forms of ROCK-II in
      primary human keratinocytes. We report that blocking ROCK function results in
      inhibition of keratinocyte terminal differentiation and an increase in cell
      proliferation. In contrast, activation of ROCK-II in keratinocytes results in
      cell cycle arrest and an increase in the expression of a number of genes
      associated with terminal differentiation. Thus, these results indicate that ROCK
      plays a critical role in regulating the balance between proliferation and
      differentiation in human keratinocytes.

PMID- 14680636
TI  - EST analysis of the cnidarian Acropora millepora reveals extensive gene loss and
      rapid sequence divergence in the model invertebrates.
AB  - A significant proportion of mammalian genes are not represented in the genomes of
      Drosophila, Caenorhabditis or Saccharomyces, and many of these are assumed to
      have been vertebrate innovations. To test this assumption, we conducted a
      preliminary EST project on the anthozoan cnidarian, Acropora millepora, a basal
      metazoan. More than 10% of the Acropora ESTs with strong metazoan matches to the
      databases had clear human homologs but were not represented in the Drosophila or
      Caenorhabditis genomes; this category includes a surprising diversity of
      transcription factors and metabolic proteins that were previously assumed to be
      restricted to vertebrates. Consistent with higher rates of divergence in the
      model invertebrates, three-way comparisons show that most Acropora ESTs match
      human sequences much more strongly than they do any Drosophila or Caenorhabditis
      sequence. Gene loss has thus been much more extensive in the model invertebrate
      lineages than previously assumed and, as a consequence, some genes formerly
      thought to be vertebrate inventions must have been present in the common metazoan
      ancestor. The complexity of the Acropora genome is paradoxical, given that this
      organism contains apparently few tissue types and the simplest extant nervous
      system consisting of a morphologically homogeneous nerve net.

PMID- 14680637
TI  - Assembly of the SpoIIIE DNA translocase depends on chromosome trapping in
      Bacillus subtilis.
AB  - Sporulation in Bacillus subtilis is an attractive system in which to study the
      translocation of a chromosome across a membrane. Sporulating cells contain two
      sister chromosomes that are condensed in an elongated axial filament with the
      origins of replication anchored at opposite poles of the sporangium. The
      subsequent formation of a septum near one pole divides the sporangium unequally
      into a forespore (the smaller compartment) and a mother cell. The septum forms
      around the filament, trapping the origin-proximal region of one chromosome in the
      forespore. As a consequence, the trapped chromosome transverses the septum with
      the remainder being left in the mother cell. Next, SpoIIIE assembles at the
      middle of the septum to create a translocase that pumps the origin-distal, two
      thirds of the chromosome into the forespore. Here, we address the question of how
      the DNA translocase assembles and how it localizes to the septal midpoint. We
      present evidence that DNA transversing the septum is an anchor that nucleates the
      formation of the DNA translocase. We propose that DNA anchoring is responsible
      for the assembly of other SpoIIIE-like DNA translocases, such as those that
      remove trapped chromosomes from the division septum of cells undergoing binary
      fission.

PMID- 14680638
TI  - Seeing fearful body expressions activates the fusiform cortex and amygdala.
AB  - Darwin's evolutionary approach to organisms' emotional states attributes a
      prominent role to expressions of emotion in whole-body actions. Researchers in
      social psychology [1,2] and human development [3] have long emphasized the fact
      that emotional states are expressed through body movement, but cognitive
      neuroscientists have almost exclusively considered isolated facial expressions
      (for review, see [4]). Here we used high-field fMRI to determine the underlying
      neural mechanisms of perception of body expression of emotion. Subjects were
      presented with short blocks of body expressions of fear alternating with short
      blocks of emotionally neutral meaningful body gestures. All images had internal
      facial features blurred out to avoid confounds due to a face or facial
      expression. We show that exposure to body expressions of fear, as opposed to
      neutral body postures, activates the fusiform gyrus and the amygdala. The fact
      that these two areas have previously been associated with the processing of faces
      and facial expressions [5-8] suggests synergies between facial and body-action
      expressions of emotion. Our findings open a new area of investigation of the role
      of body expressions of emotion in adaptive behavior as well as the relation
      between processes of emotion recognition in the face and in the body.

PMID- 14680640
TI  - Role of the DRM and CMT3 methyltransferases in RNA-directed DNA methylation.
AB  - RNA interference is a conserved process in which double-stranded RNA is processed
      into 21-25 nucleotide siRNAs that trigger posttranscriptional gene silencing. In
      addition, plants display a phenomenon termed RNA-directed DNA methylation (RdDM)
      in which DNA with sequence identity to silenced RNA is de novo methylated at its
      cytosine residues. This methylation is not only at canonical CpG sites but also
      at cytosines in CpNpG and asymmetric sequence contexts. In this report, we study
      the role of the DRM and CMT3 DNA methyltransferase genes in the initiation and
      maintenance of RdDM. Neither drm nor cmt3 mutants affected the maintenance of
      preestablished RNA-directed CpG methylation. However, drm mutants showed a nearly
      complete loss of asymmetric methylation and a partial loss of CpNpG methylation.
      The remaining asymmetric and CpNpG methylation was dependent on the activity of
      CMT3, showing that DRM and CMT3 act redundantly to maintain non-CpG methylation.
      These DNA methyltransferases appear to act downstream of siRNAs, since drm1 drm2
      cmt3 triple mutants show a lack of non-CpG methylation but elevated levels of
      siRNAs. Finally, we demonstrate that DRM activity is required for the initial
      establishment of RdDM in all sequence contexts including CpG, CpNpG, and
      asymmetric sites.

PMID- 14680639
TI  - The Ro autoantigen binds misfolded U2 small nuclear RNAs and assists mammalian
      cell survival after UV irradiation.
AB  - The Ro 60 kDa autoantigen, an RNA binding protein, is a major target of the
      immune response in patients with systemic lupus erythematosus. As mice lacking Ro
      develop a lupus-like syndrome, Ro may be important for preventing autoimmunity.
      However, the cellular function of Ro, which binds small cytoplasmic RNAs of
      unknown function called Y RNAs, has been enigmatic. Ro has been proposed to
      function in 5S rRNA quality control based on experiments in Xenopus laevis
      oocytes, and a Ro ortholog enhances survival of the eubacterium Deinococcus
      radiodurans after ultraviolet irradiation. To test the general importance of
      these two observations for Ro function, we investigated the role of Ro in
      mammalian cells. We report that, in mouse embryonic stem (ES) cells, Ro binds
      variant spliceosomal U2 snRNAs. Expression of mouse U2 snRNAs in Xenopus oocytes
      reveals that binding occurs in nuclei and appears to involve recognition of
      misfolded RNA. Moreover, mouse ES cells lacking Ro exhibit decreased survival
      after ultraviolet irradiation. In irradiated cells, both Ro and a Y RNA
      accumulate in nuclei. We propose that Ro plays a general role in small RNA
      quality control and that this function is important for cell survival after
      ultraviolet irradiation.

PMID- 14680643
TI  - Funding shake-up urged.

PMID- 14680642
TI  - Human cloning action stalled.

PMID- 14680644
TI  - R. Scott Hawley.

PMID- 14680645
TI  - Return of the natives.

PMID- 14680646
TI  - Sticklebacks.

PMID- 14680647
TI  - Low down on the singing.

PMID- 14680649
TI  - Pigment patterns: fish in stripes and spots.

PMID- 14680650
TI  - Expression of limb initiation genes and clues to the morphological
      diversification of threespine stickleback.

PMID- 14680651
TI  - Meiotic recombination: too much of a good thing?

PMID- 14680652
TI  - Myelinated nerves: filling in the juxtaparanodal gap.

PMID- 14680653
TI  - Evolutionary genetics: the nature of hidden genetic variation unveiled.

PMID- 14680654
TI  - Energy balance: a new role for PPARalpha.

PMID- 14680655
TI  - Muscle differentiation: signalling cell fusion.

PMID- 14680656
TI  - Seeing touch: moving closer to the worm mechanotransduction complex.

PMID- 14680657
TI  - Nuclear pores: sowing the seeds of assembly on the chromatin landscape.

PMID- 14680658
TI  - Rhizobium symbiosis: insight into Nod factor receptors.

PMID- 14680659
TI  - Calcium influx: is Homer the missing link?

PMID- 14680660
TI  - Current challenges in clinimetrics.
AB  - Clinimetrics is a methodologic discipline that focuses on the quality of clinical
      measurements, for example, diagnostic characteristics and disease outcomes.
      Different clinimetric properties, such as reproducibility and responsiveness, are
      important in both the development and the evaluation of measurement instruments.
      This article presents a number of the current challenges in clinimetrics: there
      is much confusion with regard to terminology, clinimetric properties are
      population and situation-dependent, and the abundance of different measurement
      instruments in specific fields hampers the comparison of study results. Further
      challenges lie in the improvement of the quality of both the measurement
      instruments and the performance of the actual measurements, and the assessment of
      the suitability for use in clinical practice. From the perspective of evidence
      based medicine, it is essential to have measurement instruments that make it
      possible to detect clinically relevant improvements that are due to diagnostic
      and therapeutic interventions. Close collaboration between clinicians,
      statisticians, epidemiologists, and psychologists is necessary to guarantee
      healthy future developments in clinimetrics, serving the needs of both clinical
      research and clinical practice.

PMID- 14680661
TI  - Clinimetrics vs. psychometrics: an unnecessary distinction.
AB  - The term "clinimetrics" was introduced by Feinstein to describe an approach to
      scale development that ostensibly is different from the more traditional
      "psychometrics." I argue that, for a number of reasons, it is time for this term
      to retire from the scene. I show that the clinimetric approach is neither new nor
      unique, but is rather a subset of psychometrics. Further, because the majority of
      new developments in scale construction (e.g., new variations of the intraclass
      correlation, item response theory, structural equation modeling, and cognitive
      theories) are reported in the psychometric literature, use of the term
      "clinimetric," especially among people not exposed to traditional test theory,
      cuts them off from a rich source of information.

PMID- 14680664
TI  - Delphi as a method to establish consensus for diagnostic criteria.
AB  - BACKGROUND/OBJECTIVES: To achieve a consensus, among a panel of experts, on the
      best clinical criteria for the clinical diagnosis of carpal tunnel syndrome
      (CTS). METHODS: Experts rated the diagnostic importance of items from the
      clinical history and physical examination for CTS. The ratings were expressed on
      a 10-cm visual analog scale. The average and standard deviation of the scores for
      each item were returned to the panelists. The panel members evaluated the items a
      second time with knowledge of the group responses from the first round. The
      scores were standardized to minimize scaling variations and, after the second
      round, the items were ranked in order of importance assigned by the group.
      Cronbach's alpha was used as a measure of homogeneity for the rankings.
      Increasing homogeneity was considered to be an indication of consensus among the
      panelists. RESULTS: Cronbach's alpha increased from 0.86 after the first round to
      0.91 after the second iteration. Panelists who were relative outliers on the
      first round demonstrated a much higher correlation with the entire group after
      the second round. CONCLUSIONS: Delphi is an effective method of establishing
      consensus for certain clinical questions. Cronbach's alpha was a useful statistic
      for measuring the extent of consensus among the panel members. Delphi was chosen
      from the possible methods of group process because of its inherent feasibility.
      The absence of a need by the panelists to meet in person removed any constraint
      on the geographic location of the panel members. In addition, the anonymous
      nature of Delphi was thought to be a key factor in avoiding a result that might
      be skewed by one or more persuasive panelists. Both of these characteristics were
      felt to be particularly important to the topic on which consensus was sought, the
      clinical diagnostic criteria for CTS. This movement in the opinions of some of
      the panelists appeared to result from the feedback of information describing the
      group opinion.

PMID- 14680665
TI  - Why are patients in clinical trials of heart failure not like those we see in
      everyday practice?
AB  - BACKGROUND/OBJECTIVES: Evidence-based research has been criticized for not being
      relevant to the real world of patient care in the community, mainly because
      participants in research studies are dissimilar to those typically seen in every
      day practice. This article examines recruitment difficulties, and identifies the
      main reasons why patients with heart failure declined to participate in a
      research trial. METHODS: Postal survey of potential trial participants (n=667),
      at time of recruitment. Analysis of (1) clinical and sociodemographic
      characteristics of respondents and nonrespondents to survey, and decliners and
      consenters to participation in a randomized controlled trial. RESULTS: No
      significant differences were found between respondents and nonrespondents in
      respect to sociodemographic or clinical variables. Males (OR=1.58, CI=1.04-2.41),
      younger patients (OR=1.05, CI=1.03-1.08), and those prescribed an angiotensin
      converting enzyme (ACE) inhibitor (OR=1.68, CI=1.10-2.57) were significantly more
      likely to consent to participate. Main reasons for nonparticipation were
      perceptions of being too old, too unwell, or too busy. CONCLUSIONS: Explanations
      of the purpose of research need to counter against perceptions among participants
      and clarify the benefits and disadvantages of participating in an intervention
      study when unwell. Study design should recognize that many elderly patients have
      busy lives and caring responsibilities. Financial support for participation
      should be considered.

PMID- 14680666
TI  - Reproducibility and relative validity of the short questionnaire to assess health
      enhancing physical activity.
AB  - BACKGROUND/OBJECTIVES: The purpose of this study is to determine reproducibility
      and relative validity of the Short QUestionnaire to ASsess Health-enhancing
      physical activity (SQUASH). METHODS: Participants (36 men and 14 women, aged 27
      58) were asked to complete the SQUASH twice with an inbetween period of
      approximately 5 weeks. In addition, participants wore the Computer Science and
      Applications (CSA) Activity Monitor for a 2-week period following the first
      questionnaire. RESULTS: The Spearman correlation for overall reproducibility of
      the SQUASH was 0.58 (95%-CI 0.36-0.74). Correlations for the reproducibility of
      the separate questions varied between 0.44 and 0.96. Spearman's correlation
      coefficient between CSA readings and the total activity score was 0.45 (95%-CI
      0.17-0.66). CONCLUSIONS: In conclusion, the SQUASH is a fairly reliable and
      reasonably valid questionnaire and may be used to order subjects according to
      their level of physical activity in an adult population. Because the SQUASH is a
      short and simple questionnaire, it may proof to be a very useful tool for the
      evaluation of health enhancing physical activity in large populations.

PMID- 14680667
TI  - Evaluation of the minimal important difference for the feeling thermometer and
      the St. George's Respiratory Questionnaire in patients with chronic airflow
      obstruction.
AB  - BACKGROUND/OBJECTIVES: The chronic respiratory questionnaire (CRQ), the St.
      Georges Respiratory Questionnaire (SGRQ), and the feeling thermometer (FT)
      evaluate change in health-related quality of life (HRQL) in patients with chronic
      airflow limitation (CAL). Although the interpretability, and in particular the
      minimal important difference (MID) in score changes, is well established for the
      CRQ, this is not the case for the SGRQ and FT. The objective of our study is to
      explore the interpretation of the SGRQ and FT. METHODS: We analyzed data from 84
      patients who completed the CRQ, SGRQ, and FT before beginning pulmonary
      rehabilitation and 3 months later. We calculated correlations between the four
      CRQ domains (dyspnea, fatigue, emotional function, and mastery) and the three
      SGRQ domains (symptoms, activities, and impact), the SGRQ total score, and the
      FT. When Pearson's correlations were >/=0.5, we constructed regression equations
      and used the slope to calculate the change in SGRQ and FT score that corresponded
      to a change in CRQ score of 0.5 (the MID). Having established MID for SGRQ we
      than used a similar approach to examine the relation between the SGRQ and FT
      results. RESULTS: Comparison with the CRQ dyspnea domain suggested the MID in
      SGRQ total score is approximately 3.05 with a 95% confidence interval (95% CI)
      ranging from 0.39 to 5.71 and a change of 5.67 (95% CI 3.43-7.92) represents a
      moderate change (1.0 on the CRQ dyspnea domain). The MID for the FT based on the
      CRQ fatigue domain was 6.1 (95% CI 1.87-10.28). The FT MID based on the SGRQ
      activities domain, impacts domain, and total score were, respectively, 7.4 (95%
      CI 3.44-11.35), 5.6 (95% CI 1.6-9.64), and 5.9 (95% CI 1.97-9.78). CONCLUSIONS:
      An MID for the SGRQ approximates the previously suggested estimate of 4 on a
      scale of 0 to 100. The MID for the FT in patients with CAL is approximately 5 to
      8 units on the 0 to 100 scale. These MID estimates should facilitate
      interpretation of clinical trials in which outcome measures include the SGRQ or
      FT.

PMID- 14680668
TI  - The influence of COPD on health-related quality of life independent of the
      influence of comorbidity.
AB  - BACKGROUND/OBJECTIVES: The goal of this study was to determine the influence of
      chronic obstructive pulmonary disease (COPD) on health-related quality of life
      (HRQL) independent of comorbidity. METHODS: Patients with COPD in general
      practice, >/=40 years, were selected. To recruit controls, a random sample of
      persons without COPD and >/=40 years, was taken. HRQL was assessed with the SF-36
      and comorbidity was determined by questionnaire. RESULTS: The influence of COPD
      on HRQL independent of comorbidity (represented by adjusted regression
      coefficients) was significant for physical functioning (-27.6), role functioning
      due to physical problems (-21.6), vitality (-14.4), and general health (-25.7),
      and was minor and not significant for social functioning (-5.6), mental health (
      1.3), role functioning due to emotional problems (-2.7), and bodily pain (-2.5).
      Comorbidity contributed significantly to the HRQL of all domains (-7.6 to -27.1).
      CONCLUSIONS: COPD patients can be impaired in all domains of HRQL. However,
      impairments in physical functioning, vitality, and general health are related to
      COPD and to some extent to comorbidity, while impairments in social and emotional
      functioning do not seem to be related to COPD, but only to comorbidity.

PMID- 14680669
TI  - On crude and age-adjusted relative survival rates.
AB  - Relative survival rates, such as 5- or 10-year relative survival rates, which
      quantify "net survival" of cancer patients, are the most commonly reported
      measures of cancer outcome by cancer registries. Because relative survival rates
      vary with age for many forms of cancer, and because the age distribution of
      cancer patients varies between different populations or within one population
      over time, age adjustment of relative survival rates is often employed in
      international comparisons or in time series analyses of cancer patient survival.
      In this article, we show that derivation of crude and of age-adjusted relative
      survival rates in the traditional way is conceptually inconsistent, and that this
      inconsistency has important practical implications. We show ways to overcome this
      inconsistency in the derivation and interpretation of crude and age-adjusted
      relative survival rates.

PMID- 14680670
TI  - A changing relationship between disability and survival in the elderly
      population: differences by age.
AB  - BACKGROUND: Longitudinal studies estimating the association between disability
      and mortality in the elderly population have typically assumed disability
      constant through the follow-up study period. Current knowledge indicates that
      such assumptions may not be appropriate. Our purpose was to examine this
      association (disability and mortality) taking into account the transitions in the
      disablement process. METHODS: 1,294 participants (aged 65 and over) in the Health
      Interview Survey of Barcelona were followed up for a median of 8 years. Nine
      basic activities of daily living (ADLs) were measured at baseline and at the end
      of follow-up. Individuals were defined as "dependent" if they reported not being
      able to perform one or more of the activities without assistance. Survival
      analysis with delayed entry, age as the time variable, and disability as a time
      dependent variable was performed. RESULTS: The rates of disability had increased
      by the end of the follow-up (from 42.0 to 60.0% among women and from 30.0 to
      48.0%, among men); 7.5% of disabled women at baseline and 28.5% of men recovered
      from disability. The adjusted relative risk of dying for those with basic ADLs
      dependency varied with age: at 80 years of age it was 3.5 for women and 1.8 for
      men, while at 90 years it was 1.9 and 1.2, respectively. CONCLUSIONS: Disability
      increases monotonically over time while the risk of mortality associated with
      disability varies with gender and age. Elderly disabled women should be
      considered a target group for intervention because they show higher rates of
      disability and are less likely to recover from disability. Our results illustrate
      the need to consider disability status as a time-dependent variable, to avoid an
      underestimation of its association with mortality.

PMID- 14680671
TI  - The clustering of neonatal deaths in triplet pregnancies: application of response
      conditional multivariate logistic regression models.
AB  - BACKGROUND/OBJECTIVES: A population-based retrospective cohort study of triplet
      pregnancies was conducted to estimate individual probabilities of neonatal
      mortality (death within 28 days of birth) conditional on the number of neonatal
      deaths experienced by other infants in the triplet set. METHODS: Data on 4,697
      triplet sets (14,091 births) were derived from the U.S. 1995-1997 matched
      multiple birth file assembled by the National Center for Health Statistics.
      Response conditional multivariate logistic regression was used to model the
      association of neonatal mortality among cotriplets. To account for the
      correlation of the outcomes among cotriplets, regression parameters were
      estimated by the methodology of generalized estimating equations with robust
      variance estimates. RESULTS: Compared with a triplet where both cotriplets
      survived the neonatal period, the adjusted odds ratio and 95% confidence interval
      (CI) for a neonatal death associated with one and two cotriplet neonatal deaths
      were 1.80 (95% CI 1.06, 3.04), and 13.41 (95% CI 2.31, 77.7), respectively, after
      adjusting for birthweight and gestational age. CONCLUSIONS: These results show
      strong evidence of clustering of neonatal deaths in triplet pregnancies.

PMID- 14680672
TI  - Improved diabetes care by primary care physicians: results of a group-randomized
      evaluation of the Medicare Health Care Quality Improvement Program (HCQIP).
AB  - BACKGROUND/OBJECTIVES: Glycosylated hemoglobin (HbA1C) measurements in patients
      with diabetes mellitus contribute to glycemic control, and, therefore to lower
      diabetic complication rates. Determine if an intervention that includes claims
      based feedback about patterns of HbA1C measurement results in more frequent
      monitoring of HbA1C in diabetic Medicare beneficiaries. SUBJECTS: Primary care
      physicians in a single Southern state treating Medicare beneficiaries with
      diabetes mellitus. METHODS: A group-randomized evaluation of an intervention that
      included claims-based feedback about patterns of HbA1C measurement, educational
      materials, and practice aids. RESULTS: Rates for each quality indicator increased
      from 1996 to 1998 for both the intervention and comparison groups, although
      increases were larger for intervention counties. HbA1C testing rates increased in
      intervention counties 16.8% compared to 13.0% in the comparison counties, an
      absolute difference of 4.0% (95% CI, 0.7 to 7.3). Differences for other
      indicators were small, although positive and favoring the intervention, and
      lacked statistical significance. CONCLUSIONS: Physician interventions that
      included practice-level feedback about monitoring of glycemic control
      successfully led to improved care of diabetic Medicare beneficiaries.

PMID- 14680673
TI  - A prospective, community-based study on virologic assessment among elderly people
      with and without symptoms of acute respiratory infection.
AB  - BACKGROUND/OBJECTIVES: Community-based elderly studies concerning microbiology of
      acute respiratory infections are scarce. Data on subclinical infections are even
      totally absent, although asymptomatic persons might act as a source of
      respiratory infections. METHODS: In a 1-year community-based study, we
      prospectively investigated the possible virologic cause of acute respiratory
      infections in 107 symptomatic case episodes and 91 symptom-free control periods.
      Participants, persons >/=60 years, reported daily the presence of respiratory
      symptoms in a diary. Virologic assessment was performed by polymerase chain
      reaction (PCR) and serology. RESULTS: In 58% of the case episodes a pathogen was
      demonstrated, the most common being rhinoviruses (32%), coronaviruses (17%), and
      influenzaviruses (7%). The odds ratio for demonstrating a virus in cases with
      symptoms vs. controls without symptoms was 30.0 (95% confidence interval 10.2
      87.6). In 4% of the symptom-free control periods a virus was detected.
      CONCLUSIONS: This study supports the importance of rhinovirus infections in
      community-dwelling elderly persons, whereas asymptomatic elderly persons can also
      harbor pathogens as detected by PCR, and thus might be a source of infection for
      their environment.

PMID- 14680674
TI  - The relation of dietary patterns to future survival, health, and cardiovascular
      events in older adults.
AB  - BACKGROUND: There have been few long-term follow-up studies of older adults who
      follow different dietary patterns. METHODS: We cluster-analyzed data on dietary
      fat, fiber, protein, carbohydrate, and calorie consumption from the U.S.
      Cardiovascular Health Study (mean age=73), and examined the relationship of the
      dietary clusters to outcomes 10 years later. RESULTS: The five clusters were
      named "Healthy diet" (relatively high in fiber and carbohydrate and low in fat),
      "Unhealthy diet" (relatively high in protein and fat, relatively low in
      carbohydrates and fiber); "High Calorie," "Low Calorie," and "Low 4," which was
      distinguished by higher alcohol consumption. The clusters were strongly
      associated with demographic factors, health behaviors, and baseline health
      status. The Healthy diet cluster had the most years of life and years of healthy
      life, and the Unhealthy diet cluster had the fewest. The Low 4 cluster had the
      best cardiovascular outcomes. Differences were not usually large. CONCLUSIONS:
      Older adults who followed the healthy eating pattern had somewhat longer and
      healthier lives, and the cluster with more alcohol consumption was associated
      with fewer cardiovascular events. The unhealthy eating pattern had the worst
      outcomes.

PMID- 14680675
TI  - Diffusion of troponin testing in unstable angina patients: adoption prior to
      guideline release.
AB  - BACKGROUND: We examined diffusion of troponin testing in Medicare patients with
      unstable angina before the release of year 2000 American College of
      Cardiology/American Heart Association guidelines recommending measurement in all
      patients with acute coronary syndromes. METHODS: We identified unstable angina
      admissions from Medicare administrative files for 22 Alabama hospitals over two
      time periods: 03/1997-02/1998 and 01/99-12/1999. Data were obtained from chart
      abstraction. Patients not confirmed for unstable angina by a clinical algorithm
      were eliminated. RESULTS: For 1997-1998, 1116 (87.7%) of all identified cases
      were clinically confirmed for unstable angina, and 1176 (90.3%) were confirmed
      for 1999. In 1997-1998, 235 (21%) of unstable angina patients had troponin
      measured, compared to 822 (70%) in 1999. From 1999, patients with troponin
      measurement, vs. those without, more likely had typical angina (50.9%, 37.4%),
      chest pain on arrival (72.8%, 57.1%), and chest pain at rest (45.4%, 37.2%) and
      more often received EKG within 20 min of presentation (46.3%, 27.9%) (P<.0005 for
      all). Patients with abnormal troponin levels more often received angiotensin
      converting enzyme inhibitors (54.6%, 18.3%), cardiac catheterization (45.4%,
      31.2%), and percutaneous coronary intervention (18.6%, 4.8%) (P<.05 for all).
      These associations remained significant after multivariable adjustment for
      patient and hospital characteristics. CONCLUSIONS: This study demonstrates
      increasing and appropriate use of troponin before guideline release. Our findings
      suggest that guidelines may codify currently accepted practice rather than always
      disseminate new knowledge. The same forces that lead to guideline development and
      release may also lead to changes in clinical practice before guideline release.

PMID- 14680676
TI  - Rapid scavenging of peroxynitrous acid by monohydroascorbate.
AB  - The reaction of peroxynitrous acid with monohydroascorbate, over the
      concentration range of 250 microM to 50 mM of monohydroascorbate at pH 5.8 and at
      25 degrees C, was reinvestigated and the rate constant of the reaction found to
      be much higher than reported earlier (Bartlett, D.; Church, D. F.; Bounds, P. L.;
      Koppenol, W. H. The kinetics of oxidation of L-ascorbic acid by peroxynitrite.
      Free Radic. Biol. Med. 18:85-92; 1995; Squadrito, G. L.; Jin, X.; Pryor, W. A.
      Stopped-flow kinetics of the reaction of ascorbic acid with peroxynitrite. Arch.
      Biochem. Biophys. 322:53-59; 1995). The new rate constants at pH 5.8 are k1 = 1 x
      10(6) M(-1) s(-1) and k(-1) = 500 s(-1) for 25 degrees C and k1 = 1.5 x 10(6) M(
      1) s(-1) and k(-1) = 1 x 10(3) s(-1) for 37 degrees C. These values indicate that
      even at low monohydroascorbate concentrations most of peroxynitrous acid forms an
      adduct with this antioxidant. The mechanism of the reaction involves formation of
      an intermediate, which decays to a second intermediate with an absorption maximum
      at 345 nm. At low monohydroascorbate concentrations, the second intermediate
      decays to nitrate and monohydroascorbate, while at monohydroascorbate
      concentrations greater than 4 mM, this second intermediate reacts with a second
      monohydroascorbate to form nitrite, dehydroascorbate, and monohydroascorbate. EPR
      experiments indicate that the yield of the ascorbyl radical is 0.24% relative to
      the initial peroxynitrous acid concentration, and that this small amount of
      ascorbyl radicals is formed concomitantly with the decrease of the absorption at
      345 nm. Thus, the ascorbyl radical is not a primary reaction product. Under the
      conditions of these experiments, no homolysis of peroxynitrous acid to nitrogen
      dioxide and hydroxyl radical was observed. Aside from monohydroascorbate's
      ability to "repair" oxidatively modified biomolecules, it may play a role as
      scavenger of peroxynitrous acid.

PMID- 14680677
TI  - Methionine oxidation by peroxymonocarbonate, a reactive oxygen species formed
      from CO2/bicarbonate and hydrogen peroxide.
AB  - Kinetic and thermodynamic evidence is reported for the role of the
      peroxymonocarbonate ion, HCO4-, as a reactive oxygen species in biology.
      Peroxymonocarbonate results from the equilibrium reaction of hydrogen peroxide
      with bicarbonate via the perhydration of CO2. The kinetic parameters for HCO4-
      oxidation of free methionine have been obtained (k1 = 0.48 +/- 0.08 M(-1)s(-1) by
      a spectrophotometric initial rate method). At the physiological concentration of
      bicarbonate in blood ( approximately 25 mM), it is estimated that
      peroxymonocarbonate formed in equilibrium with hydrogen peroxide will oxidize
      methionine approximately 2-fold more rapidly than plasma H2O2 itself. As an
      example of methionine oxidation in proteins, the bicarbonate-catalyzed hydrogen
      peroxide oxidation of alpha1-proteinase inhibitor (alpha1-PI) has been
      investigated via its inhibitory effect on porcine pancreatic elastase activity.
      The second-order rate constant for HCO4- oxidation of alpha1-PI (0.36 +/- 0.06 M(
      1)s(-1)) is comparable to that of free methionine, suggesting that methionine
      oxidation is occurring. Further evidence for methionine oxidation, specifically
      involving Met358 and Met351 of the alpha1-PI reactive center loop, has been
      obtained through amino acid analyses and mass spectroscopic analyses of
      proteolytic digests of the oxidized alpha1-PI. These results strongly suggest
      that HCO4- should be considered a reactive oxygen species in aerobic metabolism.

PMID- 14680678
TI  - Thiols enhance NO formation from nitrate photolysis.
AB  - Nitrate is generally considered an inert oxidative breakdown product of nitric
      oxide (NO). Whereas it has been shown that limited amounts of NO are produced
      during the photolysis of nitrate in aqueous solution, the photochemistry of
      nitrate in biological matrices such as plasma is unknown. We hypothesized that
      thiols, which are ubiquitously present in biological systems, may significantly
      enhance NO-quantum yields from nitrate photolysis. Exposure of fresh human plasma
      to high-intensity UV-light resulted in NO-formation (19 +/- 3 nmol/l/min) as
      measured by gas phase chemiluminescence, and this signal was almost completely
      abolished by the removal of plasma N-oxides (2 +/- 1 nmol/l/min). Reconstitution
      of NOx-depleted plasma samples with a physiological concentration of nitrate, but
      not nitrite, restored photolytic NO-generation to values comparable to naive
      plasma. Addition of the thiol-reducing agent, dithiothreitol or the sulfhydryl
      bearing amino acid, L-cysteine increased NO-formation above control levels. Thiol
      blockade by either N-ethylmaleimide (NEM) or mercuric chloride (HgCl2) reduced
      basal NO formation from 19 +/- 3 to 7 +/- 2 and 4 +/- 1 nmol/l/min, respectively.
      Exposure of plasma to UV-light increased NO-adduct concentrations from 18 +/- 5
      to 1662 +/- 658 nmol/l. Collectively, our results show that thiols facilitate
      photolytic conversion of nitrate to NO and NO-adducts such as S-nitrosothiols.
      This may lead to substantial overestimation of the latter when photolysis-based
      methodologies are used for their determination. Whether this novel reaction
      channel also has in vivo relevance remains to be investigated.

PMID- 14680679
TI  - 5-nitro-gamma-tocopherol increases in human plasma exposed to cigarette smoke in
      vitro and in vivo.
AB  - We hypothesized that the high concentrations of reactive nitrogen species in
      cigarette smoke and the known stimulatory effects of cigarette smoke on the
      inflammatory immune systems would lead to the formation of 5-nitro-gamma
      tocopherol (NGT). In order to assess gamma-tocopherol nitration, human plasma was
      exposed in vitro to gas phase cigarette smoke (GPCS) or air for up to 6 h. A
      liquid chromatography-mass spectrometry (LC-MS) method was developed to
      quantitate NGT. Detector response was linear from 0.1 to 3 pmol NGT, with a
      detection limit of 20 fmol. After a 1 h lag time, 6 h plasma exposure to GPCS
      depleted approximately 75% of alpha-T, approximately 60% of gamma-T and increased
      NGT from 3 to 134 nmol/l. The increase in NGT accounted for approximately 20% of
      the gamma-T decrease. NGT also correlated (R2 = 0.9043) with nitrate
      concentrations in GPCS-exposed plasma. The physiologic relevance of NGT was
      evaluated in a group of healthy humans. Smokers (n = 15) had plasma NGT
      concentrations double those of nonsmokers (n = 19), regardless of corrections
      using lipids or gamma-T; plasma alpha-T and gamma-T concentrations were similar
      between the groups. Our results show that LC-MS can be successfully used for NGT
      quantitation in biologic samples. Importantly, NGT in smokers' plasma suggests
      that cigarette smoking causes increased nitrosative stress.

PMID- 14680680
TI  - The CYP inhibitor 1-aminobenzotriazole does not prevent oxidative stress
      associated with alcohol-induced liver injury in rats and mice.
AB  - Cytochrome P450 (CYP) 2E1 is induced by ethanol and is postulated to be a source
      of reactive oxygen species during alcoholic liver disease. However, there was no
      difference in liver pathology and radical formation between wild-type and CYP2E1
      knockout mice fed ethanol. Other CYP isoforms may contribute these effects if
      CYP2E1 is inhibited or absent. The purpose of this study was, therefore, to
      determine if blocking most of the P450 isoforms with 1-aminobenzotriazole (ABT;
      100 mg/kg i.g.), has any effect on liver damage and oxidative stress due to
      alcohol in rats and mice. Male C57BL/6 mice and Wistar rats were fed either high
      fat control or ethanol-containing enteral diet for 4 weeks. ABT had a significant
      inhibitory effect on many P450 isoforms independent of concomitant alcohol
      administration. However, ABT did not protect against liver damage due to alcohol
      in either species. Indices of oxidative stress and inflammation were also similar
      in livers from vehicle-treated and ABT-treated animals fed ethanol. In summary,
      suppression of P450 activity with ABT had no apparent effect on oxidative stress
      caused by alcohol in both rats and mice. These data support the hypothesis that
      oxidative stress and liver damage can occur independently of CYP activities in
      both rats and mice during early alcohol-induced liver injury.

PMID- 14680681
TI  - Oxidation of glutathione and cysteine in human plasma associated with smoking.
AB  - Cigarette smoking contributes to the development or progression of numerous
      chronic and age-related disease processes, but detailed mechanisms remain
      elusive. In the present study, we examined the redox states of the GSH/GSSG and
      Cys/CySS couples in plasma of smokers and nonsmokers between the ages of 44 and
      85 years (n = 78 nonsmokers, n = 43 smokers). The Cys/CySS redox in smokers (-64
      +/- 16 mV) was more oxidized than nonsmokers (- 76 +/- 11 mV; p <.001), with
      decreased Cys in smokers (9 +/- 5 microM) compared to nonsmokers (13 +/- 6
      microM; p <.001). The GSH/GSSG redox was also more oxidized in smokers (-128 +/-
      18 mV) than in nonsmokers (-137 +/- 17 mV; p =.01) and GSH was lower in smokers
      (1.8 +/- 1.3 microM) than in nonsmokers (2.4 +/- 1.0; p <.005). Although the
      oxidation of GSH/GSSG can be explained by the role of GSH in detoxification of
      reactive species in smoke, the more extensive oxidation of the Cys pool shows
      that smoking has additional effects on sulfur amino acid metabolism. Cys
      availability and Cys/CySS redox are known to affect cell proliferation, immune
      function, and expression of death receptor systems for apoptosis, suggesting that
      oxidation of Cys/CySS redox or other perturbations of cysteine metabolism may
      have a key role in chronic diseases associated with cigarette smoking.

PMID- 14680682
TI  - Proliferation and wound healing of vascular cells trigger the generation of
      extracellular reactive oxygen species and LDL oxidation.
AB  - Cell proliferation of vascular cells is a key feature in vascular biology, wound
      healing, and pathophysiological processes such as atherosclerosis and restenosis.
      In atherosclerotic intima, cell proliferation colocalizes with oxidized LDL that
      indicate a local oxidative stress. This study aims to investigate whether cell
      proliferation is causally related with extracellular ROS generation and
      subsequent LDL oxidation. Sparse proliferating endothelial and smooth muscle
      cells generate higher levels of extracellular ROS (O2*- and H2O2) and LDL
      oxidation than confluent contact-inhibited cells. During wound healing of
      confluent cell layer, cell proliferation associated with healing also induced
      enhanced extracellular ROS generation and LDL oxidation. Proliferation-associated
      extracellular ROS generation is mediated through mitogenic signaling pathways,
      involving ERK1/2 and PKC, but is independent of de novo DNA synthesis, gene
      expression and protein synthesis. Data obtained with inhibitors of oxidases
      suggest that proliferation-associated extracellular ROS are not generated by a
      single ROS-generating system and are not essential for cell proliferation. In
      conclusion, our data show that proliferating vascular cells (in sparse culture or
      during wound healing) generate high levels of extracellular ROS and LDL oxidation
      through regulation of ROS-generating systems by mitogenic signaling. This
      constitutes a link between proliferative events and oxidative stress/LDL
      oxidation in atherosclerotic lesions and restenosis.

PMID- 14680683
TI  - Reaction rate constants of superoxide scavenging by plant antioxidants.
AB  - Plant phenols may exert protective effects by scavenging superoxide, which is
      implicated in tissue damage and accelerated inactivation of vasorelaxing nitric
      oxide. Preventing the interaction of superoxide with tissue biomolecules depends
      not only on the extent of superoxide scavenging but also on scavenging velocity.
      However, information on superoxide scavenging kinetics of plant phenols is
      scarce. We describe an improved lucigenin-based chemiluminescence assay for
      kinetic analysis. The use of potassium superoxide (KO2) as a nonenzymatic
      superoxide source allowed simple and reliable determination of the second-order
      reaction rate constants between superoxide and plant antioxidants at
      physiologically relevant conditions, avoiding unspecific effects of other
      reactive oxygen species or superoxide-generating enzymes. We calculated the rate
      constants for phenols of different structures, ranging from 2.9 x 10(3) mol(-1) l
      s(-1) for morin to 2.9 x 10(7) mol(-1) l s(-1) for proanthocyanidins. Compounds
      with pyrogallol or catechol moieties were revealed as the most rapid superoxide
      scavengers, and the gallate moiety was found to be the minimal essential
      structure for maximal reaction rate constants with superoxide.

PMID- 14680684
TI  - Application of a trityl-based radical probe for measuring superoxide.
AB  - The use of triarylmethyl (trityl) free radical, TAM OX063, for detection of
      superoxide in aqueous solutions by electron paramagnetic resonance (EPR)
      spectroscopy was investigated. TAM is paramagnetic (EPR active), highly soluble
      in water and exhibits a single sharp EPR peak in aqueous media. It is also highly
      stable in presence of many oxidoreductants such as ascorbate and glutathione that
      are present in the biological systems. TAM reacts with superoxide with an
      apparent second order rate constant of 3.1 x 10(3) M(-1) s(-1). The specific
      reactivity of TAM with superoxide, which leads to loss of EPR signal, was
      utilized to detect the generation of superoxide in various chemical
      (light/riboflavin/electron/donor), enzymatic (xanthine/xanthine oxidase), and
      cellular (stimulated neutrophils) model systems. The changes in the EPR line
      width, induced by molecular oxygen, were utilized in the simultaneous
      determination of consumption of oxygen in the model systems. The effects of flux
      of superoxide and concentration of TAM on the efficiency of detection of
      superoxide were studied. The use of TAM for detection of superoxide offers unique
      advantages namely, (i) the utilization of very low concentration of the probe,
      (ii) its stability to bioreduction, and (iii) its use in the simultaneous
      determination of concentrations of superoxide and oxygen.

PMID- 14680685
TI  - Application of in vivo ESR spectroscopy to measurement of cerebrovascular ROS
      generation in stroke.
AB  - This study used an in vivo ESR spectroscopy/spin probe technique to measure
      directly the generation of reactive oxygen species (ROS) in the brain after
      cerebral ischemia-reperfusion. Transient middle cerebral artery occlusion (MCAO)
      was induced in rats by inserting a nylon thread into the internal carotid artery
      for 1 h. The in vivo generation of ROS and its location in the brain were
      analyzed from the enhanced ESR signal decay data of three intra-arterially
      injected spin probes with different membrane permeabilities. The ESR signal decay
      of the probe with intermediate permeability was significantly enhanced 30 min
      after reperfusion following MCAO, whereas no enhancement was observed with the
      other probes or in the control group. The enhanced in vivo signal decay was
      significantly suppressed by superoxide dismutase (SOD). Brain damage was barely
      discernible until 3 h of reperfusion, and was clearly suppressed with the probe
      of intermediate permeability. The antioxidant MCI-186 completely suppressed the
      enhanced in vivo signal decay after transient MCAO. These results clearly
      demonstrate that ROS are generated at the interface of the cerebrovascular cell
      membrane when reperfusion follows MCAO in rats, and that the ROS generated during
      the initial stages of transient MCAO cause brain injury.

PMID- 14680686
TI  - Manganese complexes of curcumin and its derivatives: evaluation for the radical
      scavenging ability and neuroprotective activity.
AB  - In this study, three manganese complexes of curcumin (Cp) and related compounds,
      diacetylcurcumin (AcylCp) and ethylenediamine derivative (CpED), were synthesized
      and evaluated in vitro for antilipid peroxidation and superoxide dismutase
      activity. The manganese complexes exhibited a great capacity to protect brain
      lipids against peroxidation with IC50 of 6.3-26.3 microM. All manganese complexes
      showed much greater SOD activity than their corresponding antioxidant ligands as
      well as trolox with IC50 values of 8.9-29.9 microM. AcylCp and curcumin manganese
      complexes (AcylCpCpx and CpCpx) also gave the highest inhibitory activity to H2O2
      induced cell damage (oxidative stress) at 0.1 microg/ml (< 0.2 microM) in NG108
      15 cells, which were more potent than curcumin and related compounds. The
      neuropharmacological tests in mice supported the idea that the SOD mimicking
      complexes were able to penetrate to the brain as well as their role in the
      modulation of brain neurotransmitters under the aberrant conditions. The
      complexes significantly improved the learning and memory impairment induced by
      transient ischemic/reperfusion. AcylCpCpx, CpCpx, and CpEDCpx showed significant
      protection at 6.25, 25, and 50 mg/kg (i.p.), respectively, whereas manganese
      acetate and curcumin had no effect at doses of 50 mg/kg. In addition, treatment
      of AcylCpCpx and curcumin significantly attenuated MPTP-induced striatal dopamine
      depletion in mice, which was in accordance with the increase in the density of
      dopaminergic neurons when compared with MPTP-treated mice. These results support
      the important role of manganese in importing SOD activity and consequently, the
      enhancement of radical scavenging activity. AcylCpCpx and CpCpx seem to be the
      most promising neuroprotective agents for vascular dementia.

PMID- 14680687
TI  - Spontaneous hypomorphic mutations in antioxidant enzymes of mice.
AB  - An antioxidant enzymatic system is pivotal for aerobic animals to minimize the
      damage induced by reactive oxygen species. Spontaneous mutant animals with
      altered antioxidant enzyme activity should be useful for the study of the
      function of these enzymes in vivo. We examined the nucleotide sequences of the
      genes for the major antioxidant enzymes, including catalase (Cat), superoxide
      dismutase (Sod1, Sod2, Sod3), glutathione peroxidase (Gpx1, Gpx2, Gpx3, Gpx4,
      Gpx5), and glutathione reductase (Gsr) in 10 inbred mouse strains. Nonsynonymous
      nucleotide polymorphisms were identified in all genes, except for Gpx1, Gpx3, and
      Gpx4. Notably, the SJL/J mouse strain possessed unique nucleotide substitutions
      in the Gsr and Sod2 genes, which led to Asp39Ala and Val138Met amino acid
      substitutions in GSR and SOD2, respectively. The specific activity of GSR of
      SJL/J mice was reduced to 65% of that of NZB/N mice. In vivo activity, however,
      was higher in SJL/J, due to upregulated expression of the enzyme. The SOD2
      activity in SJL/J mice was reduced to half that of other mouse strains.
      Consistent with this reduction, oxidative damage in the mitochondria was
      increased as demonstrated by a decrease of total glutathione and an increase in
      the levels of protein oxidation. These spontaneous hypomorphic alleles would be
      valuable in the study of free radical biology.

PMID- 14680688
TI  - A novel cleavage product formed by autoxidation of lycopene induces apoptosis in
      HL-60 cells.
AB  - Dietary carotenoids have been thought to have beneficial effects on human health
      through their antioxidant activity, provitamin A activity, and effects on cancer
      cell propagation. Recent studies suggest that oxidation products or metabolites
      are involved in biological activities of carotenoids. We previously reported that
      an autoxidation mixture of lycopene induced apoptosis in HL-60 human
      promyelocytic leukemia cells, but lycopene alone did not. In the present study,
      bioassay-directed fractionations of autoxidized lycopene led to isolation of a
      novel cleavage product of lycopene. Spectral analyses elucidated its structure as
      (E,E,E)-4-methyl-8-oxo-2,4,6-nonatrienal (MON), suggesting the formation through
      the oxidative cleavages at the 5, 6- and 13, 14-double bonds of lycopene. MON was
      proved to cause a dose-dependent reduction of viability in HL-60 cells with
      morphological changes such as chromatin condensation and nuclear fragmentation.
      Treatment of HL-60 cells with MON could induce DNA fragmentation and increase
      apoptotic cells in a time- and dose-dependent manner. The MON treatment could
      enhance both caspase 8 and caspase 9 activities. Moreover, it reduced the
      expression of Bcl-2 and Bcl-XL proteins, whereas it had no effect on the level of
      Bax protein. These results clearly indicated that MON induced apoptosis in HL-60
      cells, associated with the down regulation of Bcl-2 and Bcl-XL and the activation
      of caspase cascades. The concentration of MON attained by treatment of the
      autoxidized lycopene preparation was far less than the IC50 (10 microM) value of
      MON alone in reducing the viability of HL-60 cells. The fractionation of the
      oxidized lycopene indicated the presence of other active oxidation products.
      Thus, unidentified products as well as MON would be responsible for the apoptosis
      inducing activity of the autoxidized lycopene.

PMID- 14680689
TI  - Cold-induced apoptosis of hepatocytes: mitochondrial permeability transition
      triggered by nonmitochondrial chelatable iron.
AB  - We previously described that the cold-induced apoptosis of cultured hepatocytes
      is mediated by an increase in the cellular chelatable iron pool. We here set out
      to assess whether a mitochondrial permeability transition (MPT) is involved in
      cold-induced apoptosis. When cultured hepatocytes were rewarmed after 18 h of
      cold (4 degrees C) incubation in cell culture medium or University of Wisconsin
      solution, the vast majority of cells rapidly lost mitochondrial membrane
      potential. This loss was due to MPT as assessed by confocal laser scanning
      microscopy and as evidenced by the inhibitory effect of the MPT inhibitors
      trifluoperazine plus fructose. The occurrence of the MPT was iron-dependent: it
      was strongly inhibited by the iron chelators 2,2'-dipyridyl and deferoxamine.
      Addition of trifluoperazine plus fructose also strongly inhibited cold-induced
      apoptosis, suggesting that the MPT constitutes a decisive intermediate event in
      the pathway leading to cold-induced apoptosis. Further experiments employing the
      non-site-specific iron indicator Phen Green SK and specifically mitochondrial
      iron indicators and chelators (rhodamine B-[(1,10-phenanthrolin-5
      yl)aminocarbonyl]benzyl ester, RPA, and rhodamine B-[(2,2'-bipyridin-4
      yl)aminocarbonyl]benzyl ester, RDA) suggest that it is the cold-induced increase
      in cytosolic chelatable iron that triggers the MPT and that mitochondrial
      chelatable iron is not involved in this process.

PMID- 14680690
TI  - Increased disease activity in eNOS-deficient mice in experimental colitis.
AB  - Oral dextran sodium sulfate (DSS, 3%) produces experimental colitis with many
      features of human inflammatory bowel disease (IBD), (leukocyte extravasation,
      cachexia, and histopathology). Previous studies suggest that the inducible nitric
      oxide synthase (iNOS) in blood cells or in the endothelium contribute to this
      injury. However, until now no study has been performed to directly evaluate the
      role of endothelial nitric oxide synthase (eNOS) in IBD. We compared disease
      activity in wild-type (eNOS+/+) and eNOS-deficient (eNOS-/-) mice in the DSS
      model of colitis. Administration of DSS induced weight loss, stool blood, and
      overt histopathology in both mouse strains. Disease activity was dramatically
      increased in eNOS-/- mice compared to wild types. Histologically, eNOS-deficient
      mice had greater leukocyte infiltration, gut injury, and expressed higher levels
      of the mucosal addressin, MAdCAM-1. These results demonstrate that eNOS plays an
      important role in limiting injury to the intestine during experimental colitis
      and altered eNOS content and/or activity may contribute to human IBD.

PMID- 14680691
TI  - Evaluation of two recovery methods for detection of Mycobacterium avium subsp.
      paratuberculosis by PCR: direct-dilution--centrifugation and C(18)
      carboxypropylbetaine processing.
AB  - A duplex polymerase chain reaction (PCR)-hybridization assay based on
      Mycobacterium avium subsp. paratuberculosis (MAP)-specific IS900 integration
      sites was used to evaluate two mycobacterial recovery methods from bovine feces:
      a direct-dilution-centrifugation method and a C(18)-carboxypropylbetaine (CB-18)
      based method. All MAP PCR results were confirmed for absence of inhibitors using
      a novel PCR system based on the rpoB gene of plant chloroplasts as an internal
      control. The detection limits of both MAP recovery methods when coupled with PCR
      were determined to be between 100 and 1000 organisms. Using culture as a 'gold
      standard' PCR following the direct-dilution-centrifugation protocol was 92.6%
      sensitive and 83.7% specific, whereas PCR following the CB-18 method was 100%
      sensitive and 53.5% specific. Both methods were 100% specific when 60 'true'
      negatives from two uninfected herds were tested. Both the CB-18 and direct
      processing methods coupled with a target-specific amplification technique may
      provide greater sensitivity to diagnose subclinical animals as they were able to
      detect more positives, on samples derived from infected herds, than conventional
      culture methods; however, more extensive investigation and follow-up of suspect
      animals will be required to fully validate the MAP recovery and molecular
      detection protocols described.

PMID- 14680692
TI  - Identification of fast and slow growing rhizobia nodulating soybean (Glycine max
      [L.] Merr) by a multiplex PCR reaction.
AB  - Two DNA fragments, a 730-bp and a 900-bp fragment, one homologous to host
      cultivar specificity genes nolBT of Sinorhizobium fredii and the other one
      homologous to RSalpha, an insertion-like sequence present in Bradyrhizobium
      japonicum, were generated by polymerase chain reaction (PCR) with two pairs of
      primers. The amount of each fragment generated by the multiplex PCR was
      proportional to the amount of template DNA present. The amplification of the 900
      bp RSalpha fragment was more sensitive, since it was amplified from a smaller
      amount of template DNA than the 730-bp nolBT fragment. By running the multiplex
      reaction in the presence of template DNA isolated from different sources, we
      confirmed that the reaction can discriminate between S. fredii, Bradyrhizobium
      japonicum and Sinorhizobium xinjiangensis.

PMID- 14680693
TI  - Hypertonic signal promotes stability of Dictyostelium spores via a PKA
      independent pathway.
AB  - Differentiation of Dictyostelium spores initiates with rapid encapsulation of
      prespore cells under the control of cAMP-dependent protein kinase (PKA), followed
      by further maturation processes involving cytoskeletal reorganization.
      Constitutive activation of PKA induces precocious formation of viable spores in
      development and confers the ability to encapsulate under specific submerged
      conditions. In this study, we show that the stability of these spores depends
      upon conditions of high osmotic strength during spore differentiation, indicating
      that a hypertonic signal is required in addition to PKA to induce maturation to
      stable spores. The formation of stable spores under hypertonic conditions
      requires high cell density, suggesting the involvement of additional cellular
      signaling.

PMID- 14680694
TI  - Glucose metabolism and cell size in continuous cultures of Saccharomyces
      cerevisiae.
AB  - A detailed analysis of the cell size, monitored as protein content, has been
      performed in glucose-limited continuous cultures, so as to obtain the values of
      the average protein content for various subpopulations at different cell cycle
      stages, as a function of the growth rate. Glucose metabolism appears to affect
      cell size, since there is an increase of the average protein content of the
      population when cells produce ethanol above the critical dilution rate. If the
      production of ethanol is forced at low growth rates by the addition of formate,
      the average protein content increases. These results indicate a link between
      glucose metabolism and cell size in budding yeast, as observed for mammalian
      cells.

PMID- 14680695
TI  - Site-directed mutagenesis of NnrR: a transcriptional regulator of nitrite and
      nitric oxide reductase in Rhodobacter sphaeroides.
AB  - NnrR, a transcriptional activator and member of the CRP/FNR family of regulators,
      is responsible for controlling the expression of a number of denitrification
      genes in Rhodobacter sphaeroides 2.4.3. The apparent effector for NnrR is nitric
      oxide, and in its presence NnrR activates expression of the nirK gene and the nor
      operon, encoding nitrite reductase and nitric oxide reductase, respectively.
      Whether nitric oxide directly interacts with NnrR to activate transcription is
      unknown. Other denitrifiers carry putative orthologs of NnrR. To gain insight
      into NnrR function, a number of conserved residues were mutagenized. The impact
      of these changes on NnrR function was assessed by monitoring expression of a nirK
      lacZ fusion. In this way a region spanning from Tyr93 to Cys103 that contains
      residues critical for NnrR activity was identified.

PMID- 14680696
TI  - Characterization of a suppressor mutation complementing an acid-sensitive
      mutation in Streptococcus mutans.
AB  - We isolated a spontaneous suppressor mutant complementing the acid-sensitive
      phenotype of Streptococcus mutans strain Tn-1, a mutant previously generated in
      this laboratory, defective in the activity of the dgk-encoded putative
      undecaprenol kinase. A relatively simple genetic method was developed to identify
      the suppressor mutation, based on selection for transformants containing two
      closely linked markers: a selectable allele of the unknown suppressor gene and an
      antibiotic resistance gene introduced on a suicide plasmid at random sites into
      the chromosome via homologous recombination. While we have not actually
      identified the original suppressor mutation, another mutated gene restoring acid
      resistance has been isolated, which suggests a possible mechanism of suppression.

PMID- 14680697
TI  - Glucose 6-phosphate dehydrogenase is required for sucrose and trehalose to be
      efficient osmoprotectants in Sinorhizobium meliloti.
AB  - Inactivation of the zwf gene in Sinorhizobium meliloti induces an osmosensitive
      phenotype and the loss of osmoprotection by trehalose and sucrose, but not by
      ectoine and glycine betaine. This phenotype is not linked to a defect in the
      biosynthesis of endogenous solutes. zwf expression is induced by high osmolarity,
      sucrose and trehalose, but is repressed by betaine. A zwf mutant is more
      sensitive than its parental strain to superoxide ions, suggesting that glucose 6
      phosphate dehydrogenase involvement in the osmotic response most likely results
      from the production of reactive oxygen species during osmotic stress.

PMID- 14680698
TI  - Production of free and organic iodine by Roseovarius spp.
AB  - Two strains of iodine-producing bacteria were isolated from marine samples. 16S
      rRNA gene sequences indicated the strains were most closely related to
      Roseovarius tolerans, and phylogenetic analysis indicated both belong to the same
      genus. 5 mM iodide inhibited the growth of strain 2S5-2 almost completely, and of
      strain S6V slightly. Both strains produced free iodine and organic iodine from
      iodide. CH2I2, CHI3 and CH2ClI were the main organic iodines produced by strain
      2S5-2, and CHI3 and CH2I2 by strain S6V. Experiments using cells and spent media
      suggested that the organic iodines were produced from the compounds released or
      contained in the media and cells were necessary for the considerable production
      of CH2I2 and CH2ClI, though CHI3 was produced by spent media with H2O2 or free
      iodine.

PMID- 14680699
TI  - Allelic exchange in Francisella tularensis using PCR products.
AB  - We describe here a technique for allelic exchange in Francisella tularensis
      subsp. novicida utilizing polymerase chain reaction (PCR) products. Linear PCR
      fragments containing gene deletions with an erythromycin resistance cassette
      insertion were transformed into F. tularensis. The subsequent ErmR progeny were
      found to have undergone allelic exchange at the correct location in the genome;
      the minimum flanking homology necessary was 500 bp. This technique was used to
      create mglA, iglC, bla, and tul4 mutants in F. tularensis subsp. novicida
      strains. The mglA and iglC mutants were defective for intramacrophage growth, and
      the tul4 mutant lacked detectable Tul4 by Western immunoblot, as expected.
      Interestingly, the bla mutant maintained resistance to ampicillin, indicating the
      presence of multiple ampicillin resistance genes in F. tularensis.

PMID- 14680700
TI  - Collagen-induced STAT family members activation in Entamoeba histolytica
      trophozoites.
AB  - The interaction of Entamoeba histolytica trophozoites with collagen type I and
      calcium induces a membrane to nuclei signaling. The transduction pathways
      involved in such phenomena are still poorly understood. Using a combination of
      immunoprecipitation assays, Western immunoblot analysis, electrophoretic mobility
      shift assays and immunocytochemistry we demonstrate here the expression, tyrosine
      phosphorylation, nuclear translocation and DNA binding of two members of the
      signal transducers and activators of transcription family of inducible
      transcription factors in the protozoan parasite E. histolytica. These results
      support the notion that the interaction of the extracellular matrix components
      with the parasite turns on a genetic program that facilitates the invasion of the
      host.

PMID- 14680701
TI  - Efficient switching of mycobacteriophage L5-based integrating plasmids in
      Mycobacterium tuberculosis.
AB  - We previously used a mycobacteriophage L5-derived integrating vector to
      demonstrate that glnE and aroK are essential genes in Mycobacterium tuberculosis
      by showing that we were unable to excise the integrated vector when it carried
      the only functional copy of these genes. We tested three systems to replace the
      integrated copy with alternative alleles. The most efficient method was to
      transform the strain with a second copy of the integrating vector. Excision of
      the resident vector and integration of the incoming vector occurred at an
      extremely high efficiency. This technique will allow us to study the role and
      functionality of essential genes in this important human pathogen.

PMID- 14680702
TI  - Cloning and heterologous expression of a broad specificity aminotransferase of
      Leishmania mexicana promastigotes1.
AB  - We have previously reported that Leishmania mexicana promastigotes possess a
      broad substrate specificity aminotransferase (BSAT), able to transaminate
      aspartate, aromatic amino acids, methionine and leucine. We have confirmed now
      this unusual substrate specificity by cloning its gene and expressing in
      Escherichia coli the recombinant active protein. The amino acid sequence of BSAT
      shares over 40% identity with other eukaryotic and prokaryotic aspartate
      aminotransferases, thus showing that the enzyme belongs to the subfamily Ialpha
      of aminotransferases, and has only 6% identity with the tyrosine aminotransferase
      from Trypanosoma cruzi, which has a similar substrate specificity. The production
      of recombinant active enzyme in good yields opens up the possibility of obtaining
      its 3D-structure, in order to investigate the structural basis of the broad
      substrate specificity.

PMID- 14680703
TI  - Cloning and molecular characterization of a unique hemolysin gene of Vibrio
      pommerensis sp. nov.: development of a DNA probe for the detection of the
      hemolysin gene and its use in identification of related Vibrio spp. from the
      Baltic Sea.
AB  - A group of hemolytic Vibrio strains was isolated from surface water of the Baltic
      Sea in 1995. A typical representative strain, CH-291, was found to lyse washed
      human and animal erythrocytes. Hemolysis was found to be calcium-dependent and
      occurred over a temperature range from 25 to 37 degrees C. The hemolysin-encoding
      genes were identified by screening a genomic library of total DNA from strain CH
      291. A cloned chromosomal DNA fragment of 15.6 kb conferred to Escherichia coli
      DH5alpha a hemolytic phenotype. Hybridization and sequence analysis showed the
      cloned sequence to be unique to these Baltic Sea Vibrio isolates and therefore
      provides a useful marker for their identification. Moreover, the cloned 15.6-kb
      DNA fragment possessed structural features typical for genetic islands, including
      a decreased GC content and a flanking cryptic insertion sequence element.

PMID- 14680704
TI  - Branching of o-nitrobenzoate degradation pathway in Arthrobacter protophormiae
      RKJ100: identification of new intermediates.
AB  - We have earlier reported a novel reductive pathway for o-nitrobenzoate (ONB)
      degradation (at 0.5 mM) in Arthrobacter protophormiae RKJ100, which proceeds via
      the formation of o-hydroxylaminobenzoate (HABA) and anthranilate (AA). During
      growth of this organism at 40 times higher concentration (20 mM) of ONB, 3
      hydroxyanthranilate (HAA) was identified as an intermediate by thin layer
      chromatography, gas chromatography and high performance liquid chromatography
      studies. Crude cell extracts of ONB-grown cells showed HAA 3,4-dioxygenase
      activity suggesting HAA as a terminal aromatic intermediate of the catabolic
      energy-yielding pathway as shown before in Pseudomonas fluorescens strain KU-7.
      HAA is further cleaved to 2-amino-3-carboxymuconic-6-semialdehyde by the action
      of HAA 3,4-dioxygenase. In this report we propose that ONB degradation occurs via
      the formation of HABA and the pathway branches at this point to form the two
      different aromatic intermediates AA and HAA by the action of a reductase and a
      mutase, respectively.

PMID- 14680705
TI  - Applicability of a rapid duplex real-time PCR assay for speciation of
      Campylobacter jejuni and Campylobacter coli directly from culture plates.
AB  - A rapid duplex real-time polymerase chain reaction (PCR) assay for speciation of
      Campylobacter jejuni and Campylobacter coli using the ABI Prism 7700 sequence
      detection system (Applied Biosystems) was developed based on two of the genes
      used in a conventional multiplex PCR. A rapid turnaround time of 3 h was achieved
      with the use of boiled cell lysates. Applicability of the assay was tested with
      6015 random campylobacter strains referred to the Campylobacter Reference Unit,
      with 97.6% being identified as either C. jejuni or C. coli by this technique.
      Rapidity, combined with specificity and sensitivity, makes this method for
      routine campylobacter speciation attractive to any laboratory with a Taqman
      system.

PMID- 14680706
TI  - Isolation of Arcobacter species from animal feces.
AB  - A previously developed Arcobacter isolation protocol for poultry skin and meat
      was validated for the isolation of Arcobacter from feces of livestock animals.
      Good repeatability, in-lab reproducibility and sensitivity were achieved and the
      specificity was improved by additional incorporation of cycloheximide and
      increase of the novobiocin concentration in the selective supplement. The limit
      of detection of quantitative and qualitative analysis was 10(2) and 10(0) cfu g(
      1) feces, respectively. From fecal samples collected at slaughterhouse,
      Arcobacter was isolated from 43.9% of porcine, 39.2% of bovine, 16.1% of ovine
      and 15.4% of equine samples. All three animal-associated Arcobacter species were
      isolated and levels up to 10(3) cfu g(-1) feces were determined.

PMID- 14680707
TI  - The use of amplified fragment length polymorphism for molecular analysis of
      Beauveria bassiana isolates from Kenya and other countries, and their correlation
      with host and geographical origin.
AB  - Beauveria spp. (one Beauveria sp., two B. brongniartii, and 47 B. bassiana)
      isolated from insects and soil from Kenya and other 16 different countries, were
      obtained from the CABI Bioscience Genetic Resource Collection. DNA was extracted
      from the 50 isolates and their genetic variability was investigated using
      restriction analysis of the internal-transcribed-spacer ribosomal region
      restriction fragment length polymorphism (ITS-RFLP), ITS sequencing, and
      amplified fragment length polymorphism (AFLP). The B. bassiana isolates could not
      be distinguished by ITS-RFLP as all of them showed the same banding pattern.
      However, the AFLP technique provided more information on polymorphism between the
      isolates, allowing them to be clustered by relative similarity using band
      matching and unweighted pair group method with arithmetic mean analysis. Although
      no significant correlation between the isolates and host and geographical origins
      were observed, the technique revealed clonal populations of B. bassiana within
      Kenya.

PMID- 14680709
TI  - The insecticidal toxin makes caterpillars floppy 2 (Mcf2) shows similarity to
      HrmA, an avirulence protein from a plant pathogen.
AB  - The Photorhabdus luminescens W14 toxin encoding gene makes caterpillars floppy
      (mcf) was discovered due to its ability to kill caterpillars when expressed in
      Escherichia coli. Here we describe a homologue of mcf (renamed as mcf1), termed
      mcf2, discovered in the same genome. The mcf2 gene predicts another large toxin
      whose central domain, like Mcf1, also shows limited homology to Clostridium
      cytotoxin B. However, the N-terminus of Mcf2 shows significant similarity to the
      type-III secreted effector HrmA from the plant pathogen Pseudomonas syringae and
      no similarity to the N-terminus of Mcf1. HrmA is a plant avirulence gene whose
      transient expression in tobacco cells results in cell death. Here we show that E.
      coli expressing Mcf2 can, like E. coli expressing Mcf1, kill insects. Further,
      expression of the c-Myc tagged N-terminus of Mcf2, the region showing similarity
      to HrmA, results in nuclear localisation of the fusion protein and subsequent
      destruction of transfected mammalian cells. The Mcf1 and Mcf2 toxins therefore
      belong to a family of high molecular mass toxins, differing at their N-termini,
      which encode different effector domains.

PMID- 14680708
TI  - Identification of superantigen genes speM, ssa, and smeZ in invasive strains of
      beta-hemolytic group C and G streptococci recovered from humans.
AB  - Group C and G Streptococcus dysgalactiae subspecies equisimilis (GCSE and GGSE)
      cause a substantial percentage of invasive disease caused by beta-hemolytic
      streptococci. To determine whether Streptococcus pyogenes superantigen (SAg)
      genes commonly exist within these organisms, 20 recent invasive GCSE and GGSE
      human isolates and one group G Streptococcus canis human isolate were tested for
      the presence of SAg genes speH, speJ, speL, speM, ssa and smeZ by polymerase
      chain reaction (PCR). Prior to this work, sequence-based evidence of the speM,
      ssa, and smeZ genes in GCSE, GGSE, and S. canis had not been documented. Eleven
      of the 21 isolates were PCR-positive for the presence of one to two of the SAgs
      speM, ssa, or smeZ, with four of these isolates carrying ssa+speM or ssa+smeZ. No
      isolate was positive for speH, speJ and speL. All six ssa-positive GGSE strains
      harbored the ssa3 allele, previously only found among S. pyogenes strains. All
      three smeZ-positive GGSE isolates carried one of two smeZ alleles previously only
      found within S. pyogenes, however the single S. canis isolate carried a new smeZ
      allele. All five GCSE and GGSE speM-positive isolates harbored a newly discovered
      speM allele. The identification of these SAgs within S. dysgalactiae subsp.
      equisimilis and S. canis with identical or near-identical sequences to their
      counterparts in S. pyogenes suggests frequent interspecies gene exchange between
      the three beta-hemolytic streptococcal species.

PMID- 14680710
TI  - Detection and sequencing of the microcystin LR-degrading gene, mlrA, from new
      bacteria isolated from Japanese lakes.
AB  - mlrA is the only microcystin-degrading gene detected in Sphingomonas sp. MJ-PV.
      The gene has an extremely rare nucleotide sequence and homologous genes have not
      yet been discovered in the DNA database. We discovered the existence of a gene
      homologous to mlrA in new microcystin-degrading bacteria, MD-1 and Y2. These
      strains possessed mlrA homologues, and the identities of the genes of MD-1 and Y2
      with the corresponding MJ-PV exceeded 98% and 84%, respectively. On the other
      hand, the mlrA gene was not detected in laboratory strains of the closely related
      Sphingomonas spp. strains employing hemi-nested polymerase chain reaction
      detection using two primer sets. Although the microcystin-degrading bacteria were
      closely related strains, they did not cluster together as the same species. We
      can conclude that the mlrA gene is conserved in three different bacterial
      species, and it is unique to microcystin degraders but not to the genus
      Sphingomonas.

PMID- 14680711
TI  - The spirochetal chpK-chromosomal toxin-antitoxin locus induces growth inhibition
      of yeast and mycobacteria.
AB  - Toxin-antitoxin systems encoded by bacterial plasmids and chromosomes typically
      consist of a toxin that inhibits growth of the host cell and a specific
      antitoxin. In this report, the chpK gene from the chromosomal toxin-antitoxin
      locus of the spirochete Leptospira interrogans was studied in both prokaryotic
      and eukaryotic systems. Cloning of the the spirochetal chpK gene into a
      mycobacterial expressing vector led to dramatic reductions of transformation
      efficiency in both Mycobacterium smegmatis and Mycobacterium bovis BCG. However,
      few mycobacterial transformants were obtained. This result could be due to
      plasmid structural modifications leading to disruption of chpK expression,
      suggesting that L. interrogans ChpK is highly toxic for mycobacteria. Presence of
      the L. interrogans chpK gene was also found to inhibit cell growth of the yeast
      Saccharomyces cerevisiae. These results show that ChpK possesses a broad activity
      against both prokaryotes and eukaryotes, suggesting that the cellular target of
      the toxin is conserved in these organisms.

PMID- 14680712
TI  - Localisation of Helicobacter pylori catalase in both the periplasm and cytoplasm,
      and its dependence on the twin-arginine target protein, KapA, for activity.
AB  - Helicobacter pylori induces a severe inflammatory response in the gastric mucosa.
      It is able to withstand the inflammatory response by producing proteins such as
      KatA and KapA. The C-terminus of KatA possesses a unique tetra-lysine motif not
      found in other catalases or other known protein sequences. Mutants deficient in
      this motif were constructed by site-directed mutagenesis. Cytoplasmic and
      periplasmic catalase activities were measured for the parental strain, a
      truncated KatA mutant (deficient in the unique C-terminal tetra-lysine motif) and
      a previously constructed KapA-deficient mutant (confirming previous observations
      regarding the possible periplasmic localisation of KatA). No differences were
      observed in the cytoplasmic catalase activities, however, the KapA-deficient
      mutant had approximately 5.5 times less catalase activity in the periplasmic
      extract when compared to the periplasmic preparations of either parental strain
      or KatA truncated mutant. N-terminal sequencing of KatA revealed no cleaved N
      terminal signal peptide, indicating Sec-independent transport. These findings
      support previous reports that there is some form of interaction between KatA and
      KapA of H. pylori, an interaction which still needs to be characterised.

PMID- 14680713
TI  - Depressive psychopathology and adverse childhood experiences in eating disorders.
AB  - PURPOSE: The aim of this paper was to investigate the diagnostic specificity of
      the self-critical and dependent depressive experiences in a clinical sample of
      eating disorder patients and to explore the impact of adverse childhood
      experiences on these dimensions of personality. METHOD: A sample of 94 anorexic
      and 61 bulimic patients meeting DSM-IV criteria and 236 matched controls were
      assessed with the Depressive Experience Questionnaire (DEQ), the abridged version
      of the Beck Depression Inventory (BDI) and the AMDP Life Events Inventory.
      Subjects presenting a major depression or a comorbid addictive disorder were
      excluded from the sample using the Mini International Neuropsychiatric Interview
      (MINI). RESULTS: Anorexic and bulimic patients showed higher scores than controls
      on both self-criticism and dependency sub-scales of the DEQ. Bulimic patients
      scored significantly higher than anorexic patients on self-criticism and reported
      more adverse childhood experiences. Finally, negative life events correlated only
      with self-criticism in the whole sample. DISCUSSION: Differences in the DEQ Self
      Criticism between anorexics and bulimics could not be accounted for by depression
      since bulimic patients did not show higher BDI levels compared to anorexic
      patients and depressive symptoms measured with the BDI were not found to be
      significant predictors of diagnostic grouping in a logistic multiple regression.
      CONCLUSION: This study supports the diagnostic specificity of the dependent and
      self-critical depressive dimensions in eating disorders and strengthens previous
      research on the role of early experiences in the development of these disorders.

PMID- 14680714
TI  - Depressive episodes--evidence for a causal role of primary anxiety disorders?
AB  - Anxiety and depressive disorders are common mental disorders in general
      population, imposing tremendous burden on both affected persons and society.
      Moreover, comorbidity between anxiety and depressive conditions is high, leading
      to substantial disability and functional impairment. Findings consistently
      suggest that anxiety disorders are primary to depression in the majority of
      comorbid cases. Yet, the question of whether anxiety disorders are risk factors
      for depression, and potentially even causal risk factors for the first onset of
      depression, remains unresolved. Recent results have shown that anxiety disorders
      increase the risk for subsequent depression, and also affect the course of
      depression, resulting in a poorer prognosis. Further, some results suggest a dose
      response-relationship in revealing that a higher number of anxiety disorders and
      more severe impairment associated with anxiety disorders additionally increase
      the risk for subsequent depression. The goal of this paper is to review recent
      literature, summarize implications of previous findings, and suggest directions
      for future research regarding preventive and intervention strategies.

PMID- 14680715
TI  - The Spielberger Trait Anxiety Inventory measures more than anxiety.
AB  - OBJECTIVE: Researchers tried to explain the overlap between anxiety and
      depression by suggesting that some items of self-administered questionnaires were
      badly selected and that both constructs should rather be considered as
      multidimensional. Thus, we hypothesise that the Spielberger trait anxiety
      inventory (TAI) includes items related to depression. METHOD: A non-clinical
      sample of 193 subjects filled out the TAI and the Hospitalised Anxiety-Depression
      Scale. Factors were postulated on the basis of item content and submitted to
      confirmatory factor analysis (CFA). RESULTS: We found five factors: a 10-item
      anxiety factor containing three factors, a four-item unsuccessfulness factor
      correlated with the HADS anhedonia factor, and a six-item happiness factor.
      CONCLUSION: The TAI scale encompasses measures of anxiety, depression and well
      being. Consequently, the overlap with other measures of depression may result
      from item selection. This work awaits replication in independent normal and
      pathological samples.

PMID- 14680716
TI  - A 15-year follow-up study of patients with panic disorder.
AB  - BACKGROUND: Panic disorder (PD) is generally regarded as a chronic condition with
      considerable variation in severity of symptoms. AIMS: To describe the long-term
      outcome of naturalistically treated PD. METHODS: Fifty-five outpatients with PD,
      who participated in a placebo-controlled drug trial of the efficacy of alprazolam
      and imipramine 15 years ago were reassessed with the same instruments used in the
      original study. RESULTS: Complete recovery (no panic attacks and no longer on
      medication during the last 10 years) was seen in 18% of patients, and an
      additional 13% recovered but were still on medication. Fifty-one percent
      experienced recurrent anxiety attacks whereas 18% still met diagnostic criteria
      for PD. The incidence of agoraphobia decreased from 69% to 20%. Patients with
      agoraphobia at admission tended to have a poorer long-term outcome according to
      daily functioning compared with patients without agoraphobia at admission,
      although both groups reported improved daily functioning at follow-up.
      Maintenance medication was common. No benzodiazepine abuse was reported.
      CONCLUSION: PD has a favourable outcome in a substantial proportion of patients.
      However, the illness is chronic and needs treatment. The short-term treatment
      given in the drug trial had no influence on the long-term outcome.

PMID- 14680717
TI  - Differential diagnosis using the MMPI-2: Goldberg's index revisited.
AB  - BACKGROUND: The Minnesota Multiphasic Personality Inventory (MMPI-2) often
      supports clinical decision-making in complex diagnostic problems like
      differentiating neurosis from psychosis and psychosis from bipolar disorder. The
      MMPI Goldberg index, an arithmetical combination of five clinical scales, has
      been considered to provide a good estimate for discriminating between neurotic
      and psychotic profiles. Similarly, the MMPI-2 Personality Psychopathology Five
      (PSY-5) scales have been found to be useful in differentiating diagnostic
      categories. METHOD: This study evaluates these findings in a sample of
      psychiatric patients diagnosed with depressive, psychotic, or bipolar disorder
      using ANOVA and discriminant analysis. RESULTS: Results corroborate the validity
      of Goldberg's index and find MMPI-2 PSY-5 scale Disconstraint to significantly
      differentiate between psychotic and bipolar-I disorder. CONCLUSION: The MMPI-2
      Goldberg index and PSY-5 scales can offer a useful contribution to the
      differential diagnosis of depressive, psychotic and bipolar disorder.

PMID- 14680718
TI  - Sexual dysfunction among patients treated with antidepressants--a Hungarian
      retrospective study.
AB  - The authors have investigated the incidence and several aspects of sexual
      problems in Hungarian outpatients (N = 637) treated by antidepressive medication.
      In this multicentre epidemiological survey the sexual dysfunctions (SD) was
      assessed by psychiatrists using structured interviews. Seventy-eight of the
      sample has sexual problems, more than half of them mentioned SD after starting
      antidepressive medication. Comparing various groups of antidepressants, patients
      taking a RIMA compound reported the occurrence of SD not so often as in TCA or
      SSRI groups, where the rate of SD was very high. Authors pointed out that
      physicians have to pay special attention to this problem in everyday clinical
      practice, since the recognition and treatment of sexual dysfunction is critical
      for the patient's satisfaction, medication compliance and the quality of life.

PMID- 14680719
TI  - Psychological stress and cortisol secretion in anhedonic alcoholic men.
AB  - We investigated plasma cortisol in a psychological stress paradigm in seven
      weaned anhedonic alcoholics in comparison with seven age-matched healthy
      controls. Alcoholics had significantly higher mean plasma cortisol at baseline
      and no increase following a psychological stress paradigm. Anhedonic alcoholics
      judged the experimental situation less agreeable than controls. Anhedonic
      alcoholics may have blunted cortisol response to psychological stress.

PMID- 14680720
TI  - Differential effects of milnacipran, fluvoxamine and paroxetine for depression,
      especially in gender.

PMID- 14680721
TI  - Anorexia nervosa and Crohn's disease dual diagnosis: a case study.

PMID- 14680722
TI  - Dependence and chronic psychosis with D-nor-pseudoephedrine.

PMID- 14680723
TI  - The Simon Dack lecture. Cardiology: the past, the present, and the future.

PMID- 14680724
TI  - The optimal intensity of vitamin K antagonists in patients with mechanical heart
      valves: a meta-analysis.
AB  - OBJECTIVES: The purpose of this study was to compare two different intensities of
      vitamin K antagonists (VKA) among patients with mechanical heart valves using
      meta-analytic techniques. BACKGROUND: Patients with mechanical heart valves are
      at increased risk for valve thrombosis and systemic embolism, which can be
      reduced by VKA. The range of optimal intensity of VKA is still a matter of
      debate. METHODS: A computerized search in the PubMed database was made for
      relevant articles. A meta-analysis was performed of all eligible studies with
      data on the incidences of thromboembolic and bleeding complications in patients
      with mechanical heart valve prostheses during different intensities of VKA
      therapy. The studies were classified into low-intensity VKA therapy (mean target
      international normalized ratio [INR] of 3.0 or lower) or high-intensity VKA
      therapy (mean target INR above 3.0). RESULTS: Thirty-five eligible studies were
      identified, including in total 23,145 patients, who were studied for 108,792
      patient-years. For patients with an aortic valve, high intensity resulted in a
      lower incidence of thromboembolic events (risk ratio [RR] = 0.73, p < 0.0001);
      however, the incidence of bleeding was increased (RR = 1.23, p < 0.0001). In the
      mitral valve group, the incidence rate for thromboembolism was lower in the high
      intensity group (RR = 0.74, p < 0.0001), without a significantly increased
      bleeding incidence (RR = 1.08, p = 0.0524). The total number of thromboembolic
      and bleeding events was decreased in the high-intensity group compared with low
      intensity VKA therapy for both aortic and mitral valve prostheses (RR = 0.94 [p =
      0.0067] and 0.84 [p < 0.0001]), respectively. CONCLUSIONS: This meta-analysis
      shows that both aortic and mitral valves will benefit from a treatment strategy
      with a target INR higher than 3.0.

PMID- 14680725
TI  - Effects of angiotensin-converting enzyme inhibition on transient ischemia: the
      Quinapril Anti-Ischemia and Symptoms of Angina Reduction (QUASAR) trial.
AB  - OBJECTIVES: We sought to determine whether angiotensin-converting enzyme
      inhibition (ACE-I) (i.e., quinapril) prevents transient ischemia (exertional and
      spontaneous) in patients with coronary artery disease (CAD). BACKGROUND: It is
      known that ACE-I reduces the risk of death, myocardial infarction (MI), and other
      CAD-related outcomes in high-risk patients. Numerous studies have confirmed that
      ACE-I improves coronary flow and endothelial function. Whether ACE-I also
      decreases transient ischemia is unclear, because no studies have been adequately
      designed or sufficiently powered to evaluate this issue. METHODS: Using a
      randomized, double-blinded, placebo-controlled, multicenter design, we enrolled
      336 CAD patients with stable angina. None had uncontrolled hypertension, left
      ventricular (LV) dysfunction, or recent MI, and all developed
      electrocardiographic (ECG) evidence of ischemia during exercise. They were
      randomly assigned to one of two groups: 40 mg/day quinapril (n = 177) or placebo
      (n = 159) for 8 weeks. Patients then entered an additional eight-week treatment
      phase to examine the full dose range. Those assigned to 40 mg quinapril continued
      that dose and those assigned to placebo were titrated to 80 mg/day. Treadmill
      testing, the Seattle Angina Questionnaire, and ambulatory ECG monitoring were
      used to assess responses at baseline and at 8 and 16 weeks. RESULTS: The groups
      did not differ significantly at entry or in terms of indexes assessing myocardial
      ischemia at 8 or 16 weeks of treatment. In this low-risk population, ACE-I was
      not associated with serious adverse events. CONCLUSIONS: Our findings suggest
      short-term ACE-I in CAD patients without hypertension, LV dysfunction, or acute
      MI is not associated with significant effects on transient ischemia.

PMID- 14680726
TI  - Angiotensin-converting enzyme inhibitors: ischemia is not the correct measure of
      benefit.

PMID- 14680727
TI  - Catheter-based intramyocardial injection of autologous skeletal myoblasts as a
      primary treatment of ischemic heart failure: clinical experience with six-month
      follow-up.
AB  - OBJECTIVES: We report on the procedural and six-month results of the first
      percutaneous and stand-alone study on myocardial repair with autologous skeletal
      myoblasts. BACKGROUND: Preclinical studies have shown that skeletal myoblast
      transplantation to injured myocardium can partially restore left ventricular (LV)
      function. METHODS: In a pilot safety and feasibility study of five patients with
      symptomatic heart failure (HF) after an anterior wall infarction, autologous
      skeletal myoblasts were obtained from the quadriceps muscle and cultured in vitro
      for cell expansion. After a culturing process, 296 +/- 199 million cells were
      harvested (positive desmin staining 55 +/- 30%). With a NOGA-guided catheter
      system (Biosense-Webster, Waterloo, Belgium), 196 +/- 105 million cells were
      transendocardially injected into the infarcted area. Electrocardiographic and LV
      function assessment was done by Holter monitoring, LV angiography, nuclear
      radiography, dobutamine stress echocardiography, and magnetic resonance imaging
      (MRI). RESULTS: All cell transplantation procedures were uneventful, and no
      serious adverse events occurred during follow-up. One patient received an
      implantable cardioverter-defibrillator after transplantation because of
      asymptomatic runs of nonsustained ventricular tachycardia. Compared with
      baseline, the LV ejection fraction increased from 36 +/- 11% to 41 +/- 9% (3
      months, p = 0.009) and 45 +/- 8% (6 months, p = 0.23). Regional wall analysis by
      MRI showed significantly increased wall thickening at the target areas and less
      wall thickening in remote areas (wall thickening at target areas vs. 3 months
      follow-up: 0.9 +/- 2.3 mm vs. 1.8 +/- 2.4 mm, p = 0.008). CONCLUSIONS: This pilot
      study is the first to demonstrate the potential and feasibility of percutaneous
      skeletal myoblast delivery as a stand-alone procedure for myocardial repair in
      patients with post-infarction HF. More data are needed to confirm its safety.

PMID- 14680728
TI  - Stem cell therapy for myocardial repair: is it arrhythmogenic?

PMID- 14680729
TI  - Age-dependent depression in circulating endothelial progenitor cells in patients
      undergoing coronary artery bypass grafting.
AB  - OBJECTIVES: The effect of patient age on circulating endothelial progenitor cells
      (EPCs) and their mobilization during coronary artery bypass grafting (CABG) was
      assessed. BACKGROUND: The EPCs are able to contribute to reparative
      neovascularization after tissue ischemia. In experimental models, reparative
      neovascularization is impaired in senescent animals, but the role of EPCs in this
      impairment, especially in humans, is unknown. METHODS: In 50 consecutive patients
      (43 to 80 years old) with stable coronary artery disease undergoing CABG, the
      numbers of EPCs and the plasma levels of interleukin (IL)-6, IL-8, IL-10, and IL
      18, as well as vascular endothelial growth factor (VEGF) and placental growth
      factor, were determined preoperatively, after coming off bypass, and 6, 12, 24,
      and 72 h postoperatively. RESULTS: Preoperative values of EPCs were lowered with
      increasing age, similar to the lowering of plasma VEGF levels. These age
      associated decreases could not be explained by differences in atherosclerotic
      risk factors or cardiac function. Bypass surgery induced a rapid mobilization in
      EPCs, IL-6, IL-8, IL-10, and VEGF, with a peak 6 h postoperatively. Persistently
      lower levels of EPCs and VEGF throughout the observation period were observed in
      patients >69 years old, which could not be explained by differences in the
      operative procedure or inflammatory IL activation. CONCLUSIONS: Despite a
      significant increase in EPCs and release of cytochemokines during CABG, age is a
      major limiting factor for mobilization of EPCs. Further studies are necessary to
      improve the strategies for mobilization, ex vivo expansion, and re
      transplantation of EPCs in aging patients.

PMID- 14680730
TI  - Aging of progenitor cells: limitation for regenerative capacity?

PMID- 14680731
TI  - Recurrent cardiac ischemic events early after discontinuation of short-term
      heparin treatment in acute coronary syndromes: results from the Thrombolysis in
      Myocardial Infarction (TIMI) 11B and Efficacy and Safety of Subcutaneous
      Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) studies.
AB  - OBJECTIVES: The aim of this study was to determine whether discontinuation of low
      molecular-weight heparin (LMWH) treatment results in a clustering of cardiac
      ischemic events as previously observed after cessation of unfractionated heparin
      (UFH) in acute coronary syndrome (ACS) patients. BACKGROUND: Clinical trials in
      patients with ACS have shown early recurrent ischemic events after
      discontinuation of UFH treatment. We analyzed whether LMWH cessation also results
      in early ischemic recurrence events and if continuation of a fixed-dose LMWH
      prevents this complication. METHODS: The combined incidence of death, myocardial
      infarction, or urgent revascularization in the first seven days after
      discontinuation of UFH (n = 3,012), short-term enoxaparin 1 mg/kg subcutaneously
      twice a day (n = 2,011), and short-term enoxaparin followed by prolonged
      enoxaparin 60 mg subcutaneously twice a day (n = 1,075) was analyzed from the
      combined Thrombolysis In Myocardial Infarction (TIMI) 11B/Efficacy and Safety of
      Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) database in a per
      patient analysis. RESULTS: The cessation of both UFH and short-term enoxaparin
      resulted in a similar clustering of recurrent ischemic events on the first day,
      with an incidence of the primary end point of 2.8% in both groups. Of all
      recurrent events in the first week after cessation, 40% occurred in the first 24
      h. The continuation of a fixed-dose enoxaparin treatment prevented this early
      excess, with a first day incidence of 0.4% (p < 0.0001). The TIMI risk score
      characteristics predicted the incidence of early rebound ischemic events.
      CONCLUSIONS: There is significant clustering of recurrent ischemic events within
      24 h after cessation of both short-term UFH and enoxaparin treatment, and
      patients should be carefully monitored during that period. This early rebound may
      be prevented by continuation of a fixed dose of enoxaparin.

PMID- 14680732
TI  - External counterpulsation therapy improves endothelial function in patients with
      refractory angina pectoris.
AB  - OBJECTIVES: The goal of this study was to investigate the influence of short-term
      external counterpulsation (ECP) therapy on flow-mediated dilation (FMD) in
      patients with coronary artery disease (CAD). BACKGROUND: In patients with CAD,
      the vascular endothelium is usually impaired and modification or reversal of
      endothelial dysfunction may significantly enhance treatment. Although ECP therapy
      reduces angina and improves exercise tolerance in patients with CAD, its short
      term effects on FMD in patients with refractory angina pectoris have not yet been
      described. METHODS: We prospectively assessed endothelial function in 20
      consecutive CAD patients (15 males), mean age 68 +/- 11 years, with refractory
      angina pectoris (Canadian Cardiovascular Society [CCS] angina class III to IV),
      unsuitable for coronary revascularization, before and after ECP, and compared
      them with 20 age- and gender-matched controls. Endothelium-dependent brachial
      artery FMD and endothelium-independent nitroglycerin (NTG)-mediated vasodilation
      were assessed before and after ECP therapy, using high-resolution ultrasound.
      RESULTS: External counterpulsation therapy resulted in significant improvement in
      post-intervention FMD (8.2 +/- 2.1%, p = 0.01), compared with controls (3.1 +/-
      2.2%, p = 0.78). There was no significant effect of treatment on NTG-induced
      vasodilation between ECP and controls (10.7 +/- 2.8% vs. 10.2 +/- 2.4%, p =
      0.85). External counterpulsation significantly improved anginal symptoms assessed
      by reduction in mean sublingual daily nitrate consumption, compared with controls
      (4.2 +/- 2.7 nitrate tablets vs. 0.4 +/- 0.5 nitrate tablets, p <0.001 and 4.5 +/
      2.3 nitrate tablets vs. 4.4 +/- 2.6 nitrate tablets, p = 0.87, respectively) and
      in mean CCS angina class compared with controls (3.5 +/- 0.5 vs. 1.9 +/- 0.3, p
      <0.0001 and 3.3 +/- 0.6 vs. 3.5 +/- 0.5, p = 0.89, respectively). CONCLUSIONS:
      External counterpulsation significantly improved vascular endothelial function in
      CAD patients with refractory angina pectoris, thereby suggesting that improved
      anginal symptoms may be the result of such a mechanism.

PMID- 14680733
TI  - Effects of shear stress and flow pulsatility on endothelial function: insights
      gleaned from external counterpulsation therapy.

PMID- 14680734
TI  - Incremental value of myocardial viability for prediction of long-term prognosis
      in surgically revascularized patients with left ventricular dysfunction.
AB  - OBJECTIVES: We assessed the incremental long-term prognostic value of myocardial
      viability in surgically revascularized (CABG) patients with left ventricular (LV)
      dysfunction. BACKGROUND: Clinical factors, medical therapy, the degree of LV
      dysfunction, and stress-induced ischemia may affect the relative prognostic value
      of myocardial viability. METHODS: Patients with coronary disease and ventricular
      dysfunction (mean ejection fraction 33% by echocardiography, 25% by angiography)
      were studied with dobutamine echocardiography. Follow-up (mean -4.9 years) was
      obtained in 95 patients (85% triple-vessel disease) who underwent CABG. RESULTS:
      The use of angiotensin-converting enzyme inhibitors, advanced heart failure,
      rest, low- and peak-dose wall motion scores were univariate predictors of cardiac
      death. The extent of contractile reserve and ischemia were not predictive. Low
      dose score was the strongest multivariate predictor of death (p < 0.001, hazard
      ratio 6.7). A biphasic response predicted better survival (p = 0.045, hazard
      ratio 0.5). Five-year survival was better in those with extensive (low-dose score
      <2.00) versus intermediate (score 2.00 to 2.49) amounts of viable myocardium (p =
      0.019). Patients with the least viability (score > or =2.5) had the worst outcome
      (p = 0.0001 vs. those with low-dose score <2.00; p = 0.05 vs. those with score
      2.00 to 2.49). In stepwise multivariate analysis, low-dose score added
      incremental prognostic value (p = 0.024) to clinical information and rest score.
      CONCLUSIONS: Low-dose score, representing the extent of viable myocardium, has
      incremental prognostic value as a predictor of long-term outcome in CABG patients
      with LV dysfunction.

PMID- 14680735
TI  - Viability, prognosis, revascularization, and Pascal.

PMID- 14680736
TI  - Clinical efficacy of cardiac resynchronization therapy using left ventricular
      pacing in heart failure patients stratified by severity of ventricular conduction
      delay.
AB  - OBJECTIVES: We assessed the clinical efficacy of single-site left ventricular
      (LV) pacing and determined the impact of baseline conduction delay severity on
      the magnitude of benefit. BACKGROUND: Multisite biventricular pacing can improve
      heart failure (HF) symptoms in patients with an intraventricular conduction delay
      by resynchronizing abnormal ventricular contractions and improving LV systolic
      function. METHODS: Eighty-six patients with at least New York Heart Association
      functional class II HF, chronic LV systolic dysfunction, normal sinus rhythm, and
      a QRS interval over 120 ms were implanted for atrial-synchronized LV pacing. The
      single-blinded, randomized, controlled, crossover study stratified patients 1:1
      by the baseline QRS interval into long (QRS >150 ms) and short (QRS 120 to 150
      ms) groups, which were compared during a three-month period of active
      (univentricular) pacing and a three-month period of inactive (ventricular
      inhibited) pacing. The primary end point was peak oxygen consumption (VO(2))
      followed by anaerobic threshold, distance walked in 6 min, and quality-of-life
      questionnaire score. PATIENTS: Twelve patients were withdrawn before
      randomization and 17 could not complete both study periods. The short QRS group
      did not improve in any end point with active pacing. For the long QRS group, peak
      VO(2) increased 2.46 ml/min/kg (p < 0.001), the anaerobic threshold increased
      1.55 ml/min/kg (p < 0.001), the distance walked in 6 min increased 47 m (p =
      0.024), and the quality-of-life score improved 8.1 points (p = 0.004).
      CONCLUSIONS: Left ventricular pacing significantly improves exercise tolerance
      and quality of life in patients with chronic HF, LV systolic dysfunction, and a
      QRS interval over 150 ms.

PMID- 14680737
TI  - Long-term effectiveness of cardiac resynchronization therapy in patients with
      refractory heart failure and "narrow" QRS.
AB  - OBJECTIVES: The aim of the study was to evaluate the effectiveness of cardiac
      resynchronization therapy (CRT) in patients with refractory heart failure (HF)
      and incomplete left bundle branch block ("narrow" QRS), together with
      echocardiographic evidence of interventricular and intraventricular asynchrony.
      BACKGROUND: Cardiac resynchronization therapy has been proven effective in
      patients with HF and wide QRS by ameliorating contraction asynchrony. METHODS:
      Fifty-two patients with severe HF received biventricular pacing. The patients
      were eligible in the presence of echocardiographic evidence of interventricular
      and intraventricular asynchrony, regardless of QRS duration. The patient
      population was divided into group 1 (n = 38), with a QRS duration >120 ms, and
      group 2 (n = 14), with a QRS duration < or =120 ms. RESULTS: The baseline
      parameters considered in the study were similar in both groups. At follow-up, CRT
      determined narrowing of the QRS interval in the entire population and in group 1
      (p < 0.001), whereas a small increase in QRS duration was observed in group 2 (p
      = NS); in all patients and within groups, we observed improvement of New York
      Heart Association functional class (p < 0.001 in all), left ventricular ejection
      fraction (p < 0.001 in all), left ventricular end-diastolic and end-systolic
      diameter (p < 0.05 within groups), mitral regurgitation area (p < 0.001 in all),
      interventricular delay (p < 0.001 in all), and deceleration time (group 1: p <
      0.001, group 2: p < 0.05), with no significant difference between groups. The 6
      min walking test improved in both groups (group 1: p < 0.001; group 2: p < 0.01).
      CONCLUSIONS: Cardiac resynchronization therapy determined clinical and functional
      benefit that was similar in patients with wide or "narrow" QRS. Cardiac
      resynchronization therapy may be helpful in patients with echocardiographic
      evidence of interventricular and intraventricular asynchrony and incomplete left
      bundle branch block.

PMID- 14680738
TI  - Predicting cardiac resynchronization response by QRS duration: the long and short
      of it.

PMID- 14680739
TI  - Gender differences in advanced heart failure: insights from the BEST study.
AB  - OBJECTIVES: The goal of this study was to determine the influence of gender on
      baseline characteristics, response to treatment, and prognosis in patients with
      heart failure (HF) and impaired left ventricular ejection fraction (LVEF).
      BACKGROUND: Under-representation of women in HF clinical trials has limited our
      understanding of gender-related differences in patients with HF. METHODS: The
      impact of gender was assessed in the Beta-Blocker Evaluation of Survival Trial
      (BEST) which randomized 2,708 patients with New York Heart Association class
      III/IV and LVEF < or =0.35 to bucindolol versus placebo. Women (n = 593) were
      compared with men (n = 2,115). Mean follow-up period was two years. RESULTS:
      Significant differences in baseline clinical and laboratory characteristics were
      found. Women were younger, more likely to be black, had a higher prevalence of
      nonischemic etiology, higher right and left ventricular ejection fraction, higher
      heart rate, greater cardiothoracic ratio, higher prevalence of left bundle branch
      block, lower prevalence of atrial fibrillation, and lower plasma norepinephrine
      level. Ischemic etiology and measures of severity of HF were found to be
      predictors of prognosis in women and men. However, differences in the predictive
      values of various variables were noted; most notably, coronary artery disease and
      LVEF appear to be stronger predictors of prognosis in women. In the nonischemic
      patients, women had a significantly better survival rate compared with men.
      CONCLUSIONS: In HF patients with impaired LVEF, significant gender differences
      are present, and the prognostic predictive values of some variables vary in
      magnitude between women and men. The survival advantage of women is confined to
      patients with nonischemic etiology.

PMID- 14680740
TI  - A better survival for women with heart failure? It's not so simple ...

PMID- 14680741
TI  - Peak oxygen intake and cardiac mortality in women referred for cardiac
      rehabilitation.
AB  - OBJECTIVES: This study investigated the prognostic importance of measured peak
      oxygen intake (VO(2peak)) in women with known coronary heart disease referred for
      outpatient cardiac rehabilitation. BACKGROUND: Exercise capacity is a powerful
      predictor of prognosis in men with known or suspected coronary disease. Similar
      findings are described in women, but fewer studies have utilized measured
      VO(2peak), the most accurate measure of exercise capacity. METHODS: A single
      center design took data from 2,380 women, age 59.7 +/- 9.5 years (1,052
      myocardial infarctions, 620 coronary bypass procedures, and 708 with proven
      ischemic heart disease), who underwent cardiorespiratory exercise testing. They
      were followed for an average of 6.1 +/- 5 years (median 4.5 years, range 0.4 to
      25 years) until cardiac and all-cause death. RESULTS: We recorded 95 cardiac
      deaths and 209 all-cause deaths. Measured VO(2peak) was an independent predictor
      of risk, values > or =13 ml/kg/min (3.7 multiples of resting metabolic rate)
      conferring a 50% reduction in cardiac mortality (hazard ratio [HR] 0.5, p =
      0.001). Considered as a continuous variable, a 1 ml/kg/min advantage in initial
      VO(2peak) was associated with a 10% lower cardiac mortality. Adverse predictors
      were diabetes (HR 2.73, p = 0.0005) and antiarrhythmic therapy (HR 3.93, p =
      0.0001). CONCLUSIONS: As in men, measured VO(2peak) is a strong independent
      predictor of cardiac mortality in women referred for cardiac rehabilitation.

PMID- 14680742
TI  - Cardiac troponin I in acute pericarditis.
AB  - OBJECTIVES: This study was designed to investigate the prognostic value of
      cardiac troponin I (cTnI) in viral or idiopathic pericarditis. BACKGROUND:
      Idiopathic acute pericarditis has been recently reported as a possible cause of
      nonischemic release of cTnI. The prognostic value of this observation remains
      unknown. METHODS: We enrolled 118 consecutive cases (age 49.2 +/- 18.4 years; 61
      men) within 24 h of symptoms onset. A highly sensitive enzymoimmunofluorometric
      method was used to measure cTnI (acute myocardial infarction [AMI] threshold was
      1.5 ng/ml). RESULTS: A cTnI rise was detectable in 38 patients (32.2%). The
      following characteristics were more frequently associated with a positive cTnI
      test: younger age (p < 0.001), male gender (p = 0.007), ST-segment elevation (p <
      0.001), and pericardial effusion (p = 0.007) at presentation. An increase beyond
      AMI threshold was present in nine cases (7.6%), with an associated creatine
      kinase-MB elevation, a release pattern similar to AMI, and echocardiographic
      diffuse or localized abnormal left ventricular wall motion without detectable
      coronary artery disease. After a mean follow-up of 24 months a similar rate of
      complications was found in patients with a positive or a negative cTnI test
      (recurrent pericarditis: 18.4 vs. 18.8%; constrictive pericarditis: 0 vs. 1.3%,
      for all p = NS; no cases of cardiac tamponade or residual left ventricular
      dysfunction were detected). CONCLUSIONS: In viral or idiopathic acute
      pericarditis cTnI elevation is frequently observed and commonly associated with
      young age, male gender, ST-segment elevation, and pericardial effusion at
      presentation. cTnI increase is roughly related to the extent of myocardial
      inflammatory involvement and, unlike acute coronary syndromes, is not a negative
      prognostic marker.

PMID- 14680743
TI  - Meeting highlights of the 14th annual scientific sessions of the American Society
      of Echocardiography: June 11 to 14, 2003, in Las Vegas, Nevada.

PMID- 14680745
TI  - Did contrast nephropathyin RAPPID really occur?

PMID- 14680748
TI  - Should intravenous N-acetylcysteine be considered standard of care for prevention
      of radio-contrast-induced nephropathy?

PMID- 14680749
TI  - NAD(P)H oxidase in the failing human heart.

PMID- 14680752
TI  - Depression as another possible explanation for worse outcomes in myocardial
      infarction during off-hours.

PMID- 14680753
TI  - Circadian variations in outcome of primary percutaneous coronary intervention.

PMID- 14680755
TI  - Group III mGlu receptor agonists produce anxiolytic- and antidepressant-like
      effects after central administration in rats.
AB  - It was well established that compounds which decrease glutamatergic transmission
      via blockade of NMDA or group I mGlu receptors produce anxiolytic- and
      antidepressant-like action in animal tests and models. Since group III
      metabotropic glutamate receptor (mGluR) agonists are known to reduce
      glutamatergic neurotransmission by the inhibition of glutamate release, we
      decided to investigate potential anxiolytic- and/or antidepressant-like effects
      of group III mGluR agonists, after central administration in rats. It was found
      that group III mGluR agonists, (1S,3R,4S)-1-aminocyclo-pentane-1,3,4
      tricarboxylic acid (ACPT-I) and 2-amino-4-(3-hydroxy-5-methylisoxazol-4
      yl)butyric acid (HomoAMPA), given intrahippocampally, produced a dose-dependent
      anxiolytic-like effect in the conflict drinking test. The effects of ACPT-I and
      HomoAMPA were reversed by (RS)-alpha-cyclopropyl-4-phosphonophenyl glycine
      (CPPG), group III mGluR antagonist. Moreover, a dose-dependent antidepressant
      like action of group III mGluR agonists, ACPT-I and (RS)-4-phosphonophenylglycine
      (RS-PPG), but not HomoAMPA, was found in behavioral despair test, after
      intracerebroventricular injections, and the effect of ACPT-I was reversed by
      CPPG. The results obtained indicate that group III mGluR agonists produce
      anxiolytic- as well as antidepressant-like effects in behavioral tests, after
      central administration in rats. The reduction of glutamate release by group III
      mGluR activation may be a possible mechanism underlying anxiolytic- and
      antidepressant-like properties of the tested compounds. In conclusion, the
      results of our studies indicate that group III mGlu receptor agonists may play a
      role in the therapy of both anxiety and depression.

PMID- 14680756
TI  - Subtype-selective GABAergic drugs facilitate extinction of mouse operant
      behaviour.
AB  - Several recent studies have shown that reducing gamma-aminobutyric acid (GABA)
      mediated neurotransmission retards extinction of aversive conditioning. However,
      relatively little is known about the effect of GABA on extinction of appetitively
      motivated tasks. We examined the effect of chlordiazepoxide (CDP), a classical
      benzodiazepine (BZ) and two novel subtype-selective BZs when administered to male
      C57Bl/6 mice during extinction following training on a discrete-trial fixed-ratio
      5 (FR5) food reinforced lever-press procedure. Initially CDP had no effect, but
      after several extinction sessions CDP significantly facilitated extinction, i.e.
      slowed responding, compared with vehicle-treated mice. This effect was not due to
      drug accumulation because mice switched from vehicle treatment to CDP late in
      extinction showed facilitation immediately. Likewise, this effect could not be
      attributed to sedation because the dose of CDP used (15 mg/kg i.p.) did not
      suppress locomotor activity. The two novel subtype-selective BZ partial agonists,
      L-838417 and TP13, selectively facilitated extinction in similar fashion to CDP.
      The non-GABAergic anxiolytic buspirone was also tested and found to have similar
      effects when administered at a non-sedating dose. These studies demonstrate that
      GABA-mediated processes are important during extinction of an appetitively
      motivated task, but only after the animals have experienced several extinction
      sessions.

PMID- 14680757
TI  - Modulation of the locomotor responses induced by D1-like and D2-like dopamine
      receptor agonists and D-amphetamine by NMDA and non-NMDA glutamate receptor
      agonists and antagonists in the core of the rat nucleus accumbens.
AB  - Dopamine and glutamate interactions in the nucleus accumbens (NAcc) play a
      crucial role in both the development of a motor response suitable for the
      environment and in the mechanisms underlying the motor-activating properties of
      psychostimulant drugs such as amphetamine. We investigated the effects of the
      infusion in the NAcc of NMDA and non-NMDA receptor agonists and antagonists on
      the locomotor responses induced by the selective D(1)-like receptor agonist SKF
      38393, the selective D(2)-like receptor agonist quinpirole, alone or in
      combination, and D-amphetamine. Infusion of either the NMDA receptor agonist
      NMDA, the NMDA receptor antagonist D-AP5, the non-NMDA receptor antagonist CNQX,
      or the non-NMDA receptor agonist AMPA resulted in an increase in basal motor
      activity. Conversely, all of these ionotropic glutamate (iGlu) receptor ligands
      reduced the increase in locomotor activity induced by focal infusion of D
      amphetamine. Interactions with dopamine receptor activation were not so clear:
      (i). infusion of NMDA and D-AP5 respectively enhanced and reduced the increase in
      locomotor activity induced by the infusion of the D(1)-like receptor agonist of
      SKF 38393, while AMPA or CNQX decreased it; (ii). infusion of NMDA, D-AP5, and
      CNQX reduced the increase in locomotor activity induced by co-injection of SKF
      38393+quinpirole--a pharmacological condition thought to activate both D(1)-like
      and D(2)-like presynaptic and postsynaptic receptors, while infusion of AMPA
      potentiated it; (iii). infusion of either NMDA, D-AP5 or CNQX, but not of AMPA,
      potentiated the decrease in motor activity induced by the D(2)-like receptor
      agonist quinpirole, a compound believed to act only at presynaptic D(2)-like
      receptors when injected by itself. Our results show that NMDA receptors have an
      agonist action with D(1)-like receptors and an antagonist action with D(2)-like
      receptors, while non-NMDA receptors have the opposite action. This is discussed
      from a anatamo-functional point of view.

PMID- 14680758
TI  - Decreased social behaviour following 3,4-methylenedioxymethamphetamine (MDMA) is
      accompanied by changes in 5-HT2A receptor responsivity.
AB  - This study examined the involvement of the 5-HT(2A) receptor in the long-term
      anxiogenic effect of a brief exposure of young rats to 3,4
      methylenedioxymethamphetamine (MDMA) using the social interaction and elevated
      plus-maze paradigms. Wistar rats (post-natal day (PND) 28) received either MDMA
      (5 mg/kg i.p.) or saline (1 ml/kg i.p.) hourly for 4 h on 2 consecutive days.
      Locomotor activity was measured for 60 min after the first injection and core
      body temperature was recorded at regular intervals over 4 h. On PND 84, without
      further drug administration, social interaction was assessed between treatment
      matched rat pairs derived from separate litters. On PND 86, rats received either
      the 5-HT(2A/2C) receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
      (DOI, 1 mg/kg i.p.) or saline and locomotor activity, wet-dog shakes and back
      muscle contractions were monitored. The change in elevated plus-maze behaviour
      was assessed following the same injection on PND 87. Acutely, MDMA produced a
      significant hyperlocomotion and hyperthermia (p<0.01). Following 55 days of
      abstinence, social interaction was reduced by 27% in MDMA pre-treated rats
      compared with that in controls (p<0.01). On the elevated plus-maze, pre-treatment
      with MDMA prevented the anxiogenic effect of DOI. On PND 92, hippocampal, frontal
      cortical and striatal 5-hydroxytryptamine (5-HT) was significantly reduced in
      MDMA pre-treated rats by between 16% and 22%, without any accompanying change in
      [(3)H]paroxetine binding in cortical homogenates. In conclusion, exposure of
      young rats to repeated MDMA caused serotonin depletion and induced 'anxiety-like'
      behaviour in the social interaction test accompanied by a long-lasting reduction
      in specific 5-HT(2A) receptor mediated behaviour.

PMID- 14680759
TI  - Progesterone inhibition of dopamine-induced increase in frequency of spontaneous
      excitatory postsynaptic currents in rat prelimbic cortical neurons.
AB  - We examined the effects of progesterone on frequency of miniature excitatory
      postsynaptic currents (mEPSCs) and spontaneous excitatory postsynaptic currents
      (sEPSCs), and dopamine-induced increase in the frequency of sEPSCs in pyramidal
      cells of layers V-VI of the rat prelimbic cortex using whole-cell patch-clamp
      techniques in slices. The results showed that progesterone 100 microM had no
      effects on the frequency of mEPSCs and sEPSCs, but significantly inhibited
      dopamine-induced increase in frequency of sEPSCs. This was in contrast to the
      effect of progesterone on the effect of 5-HT, which showed no changes after
      progesterone. When studying the mechanism of the progesterone effect, we observed
      that GABA(A) receptor antagonist and progesterone receptor antagonist did not
      influence the effect of progesterone; progesterone had no effects on D1 receptor
      agonist, protein kinase A and protein kinase C activator-induced increase in the
      frequency of sEPSCs. Interestingly, sigma(1) receptor antagonist could inhibit
      the effect of dopamine and sigma(1) receptor agonist had a synergistic effect on
      the effect of D1 receptor agonist. These results suggest that progesterone may
      inhibit dopamine-induced increase in frequency of sEPSCs in rat prelimbic
      cortical neurons via inhibition of sigma(1)/D1 receptor synergism because
      progesterone has been known to be an antagonist of sigma(1) receptor.

PMID- 14680760
TI  - Zn2+ modulates currents generated by the dopamine transporter: parallel effects
      on amphetamine-induced charge transfer and release.
AB  - The psychostimulant drug amphetamine increases extracellular monamines in the
      brain acting on neurotransmitter transporters, especially the dopamine
      transporter. Mediated by this plasmalemmal pump, amphetamine does not only induce
      release but also charge transfer which might be involved in the release
      mechanism. To study a potential link between the two phenomena, we used Zn(2+) as
      an acute regulatory agent which modulates dopamine uptake by a direct interaction
      with the transporter protein. Charge transfer was investigated in patch-clamp
      experiments on HEK 293 cells stably expressing the human dopamine transporter,
      release was studied in superfusion experiments on cells preloaded with the
      metabolically inert transporter substrate [(3)H]1-methyl-4-phenylpyridinium. Ten
      micromoles of Zn(2+) had only minor effects in the absence of amphetamine but
      stimulated release and inward currents induced by amphetamine depending on the
      concentration of the psychostimulant: the effect of 0.2 microM was not
      significantly modulated, whereas the effect of 1 and 10 microM amphetamine was
      stimulated, and the stimulation by Zn(2+) was significantly stronger at 10 microM
      than at 1 microM amphetamine. The stimulatory action of Zn(2+) on release and
      inward current was in contrast to its inhibitory action on dopamine uptake. This
      supports a release mechanism of amphetamine different from facilitated exchange
      diffusion but involving ion fluxes through the dopamine transporter.

PMID- 14680761
TI  - Brain region and dose effects of an olanzapine/fluoxetine combination on
      extracellular monoamine concentrations in the rat.
AB  - Clinical studies of patients with treatment-resistant depression have shown that
      combined treatment with fluoxetine and olanzapine rapidly and significantly
      improved depressive symptoms. The present study used in vivo microdialysis to
      investigate the brain regional and dose effects of these drugs on extracellular
      monoamine concentrations in the rat prefrontal cortex, hypothalamus, nucleus
      accumbens and striatum. In the prefrontal cortex, the olanzapine/fluoxetine
      combination (3/10 mg/kg, respectively) increased catecholamine concentrations to
      a significantly greater extent than either drug alone (dopamine mean+/-S.E.M.
      percent of baseline: olanzapine (120 +/- 12.4), fluoxetine (123 +/- 6.2),
      combination (185 +/- 8.8); norepinephrine: olanzapine (124 +/- 7.2), fluoxetine
      (126 +/- 5.0), combination (215 +/- 15.8)). The combination also increased
      serotonin concentrations to 156 +/- 11.0% of baseline, but to a lesser extent
      than fluoxetine alone (210 +/- 14.5%). Similar synergistic effects of the
      combination were observed in the hypothalamus, but not in the other regions
      studied. The dose response effects of the drugs alone and in combination were
      complex, but larger doses of the combinations produced greater monoamine
      concentration increases than smaller dose combinations. The effects of the
      olanzapine/fluoxetine combination are meaningful in prefrontal cortex and
      hypothalamus due to their hypothesized role in the etiology and pharmacotherapy
      of depression. The wide-ranging neurochemical effects of this drug combination
      may make it particularly useful as a treatment for complex, resistant
      depressions.

PMID- 14680762
TI  - Decreased alcohol self-administration and increased alcohol sensitivity and
      withdrawal in CB1 receptor knockout mice.
AB  - Recent advances in the understanding of the neurobiological basis of alcohol
      dependence suggest that the endocannabinoid system may play a key role in the
      reinforcing effects of ethanol. In the present study, disruption of CB1 receptors
      in mice generated on a CD1 background decreased both ethanol consumption and
      preference. This decreased ethanol self-administration was associated with
      increased sensitivity to the acute intoxicating effects of ethanol. Mutant mice
      were more sensitive to the hypothermic and sedative/hypnotic effects of acute
      ethanol administration (1.5-4.0 g/kg), although plasma ethanol concentrations did
      not differ from those of controls. Moreover, wild-type mice exhibited normal
      locomotor activation caused by 1.0-2.5 g/kg injection of ethanol, whereas mutant
      mice displayed sedation in response to the injection of the same ethanol doses.
      The severity of alcohol withdrawal-induced convulsions was also increased in CB1(
      /-) mice. Our results suggest that CB1 receptors participate in the regulation of
      ethanol drinking and demonstrate that their disruption lead to increased ethanol
      sensitivity and withdrawal severity.

PMID- 14680763
TI  - Neuroprotection by a novel brain permeable iron chelator, VK-28, against 6
      hydroxydopamine lession in rats.
AB  - Significant increase in iron occurs in the substantia nigra pars compacta of
      Parkinsonian subjects, and in 6-hydroxydopamine (6-OHDA) treated rats and
      monkeys. This increase in iron has been attributed to its release from ferritin
      and is associated with the generation of reactive oxygen species and the onset of
      oxidative stress-induced neurodegeneration. Several iron chelators with
      hydroxyquinoline backbone were synthesized and their ability to inhibit basal as
      well as iron-induced mitochondrial lipid peroxidation was examined. The
      neuroprotective potential of the brain permeable iron chelator, VK-28 (5-[4-(2
      hydroxyethyl) piperazine-1-ylmethyl]-quinoline-8-ol), injected either
      intraventricularly (ICV) or intraperitoneally (IP), to 6-OHDA lesioned rats was
      investigated. VK-28 inhibited both basal and Fe/ascorbate induced mitochondrial
      membrane lipid peroxidation, with an IC(50) (12.7 microM) value comparable to
      that of the prototype iron chelator, desferal, which does not cross the blood
      brain barrier. At an ICV pretreatment dose as low as 1 microg, VK-28 was able to
      completely protect against ICV 6-OHDA (250 microg) induced striatal dopaminergic
      lesion, as measured by dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and
      homovanilic acid (HVA) levels. IP injection of rats with VK-28 (1 and 5 mg/kg)
      daily for 10 and 7 days, respectively, demonstrated significant neuroprotection
      against ICV 6-OHDA at the higher dose, with 68% protection against loss of
      dopamine at 5mg/kg dosage of VK-28. The present study is the first to show
      neuroprotection with a brain permeable iron chelator. The latter can have
      implications for the treatment of Parkinson's disease and other neurodegenerative
      diseases (Alzheimer's disease, Friedreich ataxia, aceruloplasminemia,
      Hallervorden Spatz syndrome) where abnormal iron accumulation in the brain is
      thought to be associated with the degenerative processes.

PMID- 14680764
TI  - Prevention of fentanyl-induced delayed pronociceptive effects in mice lacking the
      protein kinase Cgamma gene.
AB  - It has recently been reported in several nociceptive models of rats that the
      antinociceptive effect of fentanyl, an opioid analgesic widely used in the
      management of per-operative pain, was followed by paradoxical delayed
      hyperalgesia dependent on N-methyl-D-aspartate (NMDA) mechanisms. Events upstream
      of the NMDA receptor, especially the activation of the protein kinase Cgamma
      (PKCgamma), have been involved in the persistence of pain states associated with
      central sensitisation. In order to evaluate the contribution of the PKCgamma in
      early and delayed fentanyl nociceptive responses, we studied these effects in
      knock-out mice deficient in such a protein. We found that fentanyl
      antinociception was followed by the spontaneous appearance of prolonged
      hyperalgesia in the paw pressure and formalin tests, and allodynia in the Von
      Frey paradigm. In PKCgamma deficient mice, an enhancement of the early fentanyl
      antinociceptive effects was observed, as well as a complete prevention of the
      fentanyl delayed hyperalgesic/allodynic effects. Finally, naloxone administration
      in mice that had recovered their pre-fentanyl nociceptive threshold, precipitated
      hyperalgesia/allodynia in wild-type but not in mutant mice. This study identifies
      the PKCgamma as a key element that links opioid receptor activation with the
      recruitment of opposite systems to opioid analgesia involved in a physiological
      compensatory pain enhancement.

PMID- 14680765
TI  - Differentiation of substrate and non-substrate inhibitors of transport system xc(
      ): an obligate exchanger of L-glutamate and L-cystine.
AB  - In addition to the well-characterized sodium-dependent excitatory amino acid
      transporters (EAATs) present in the mammalian CNS, a chloride-dependent, sodium
      independent transporter has also been identified that is capable of mediating the
      uptake of L-glutamate. Named system x(c)(-), this transporter is an obligate
      exchanger that normally couples the export of intracellular L-glutamate with the
      import of extracellular L-cystine. Two cell lines that express high levels of
      system x(c)(-) are used to delineate the pharmacology of the transporter and
      demonstrate that it is distinct from both the EAATs and EAA ionotropic receptors.
      Potent competitive inhibitors of system x(c)(-) include: L-homocysteate,
      ibotenate, L-serine-O-sulphate, (RS)-4-bromohomoibotenate, quisqualate, and (S)-4
      carboxyphenylglycine. A fluorescent-based assay that allows system x(c)(-)
      mediated exchange of L-glutamate and L-cystine to be followed in real time is
      used to assess substrate activity. Interestingly, those compounds that proved to
      be the most potent competitive inhibitors (e.g. L-quisqualate and 4-S-CPG) also
      proved to be the least active as substrates, suggesting that distinct structural
      features may control binding and translocation. Lastly, the finding that a number
      of system x(c)(-) inhibitors are also commonly used as probes of excitotoxic
      pathology (e.g., L-quisqualate, ibotenate and L-homocysteate) raises some
      interesting questions regarding the mechanisms through which these analogues
      produce CNS damage.

PMID- 14680766
TI  - Bicuculline free base blocks voltage-activated K+ currents in rat medial preoptic
      neurons.
AB  - The effects of the well-known GABA(A)-receptor blocker bicuculline on voltage
      gated K(+) currents were studied in neurons from the medial preoptic nucleus
      (MPN) of rat. Whole-cell currents were recorded using the perforated-patch
      technique. Voltage steps from -54 to +6 mV resulted in tetraethylammonium
      sensitive K(+) currents of delayed rectifier type. The total K(+) current (at 300
      ms), including Ca(2+)-dependent and Ca(2+)-independent components, was reversibly
      reduced (17 +/- 4%) by 100 microM bicuculline methiodide and (37 +/- 5%) by 100
      microM bicuculline as free base. The Ca(2+)-independent fraction (77 +/- 2%) of
      K(+) current evoked by a voltage step was, however, reduced (54 +/- 6%) only by
      bicuculline free base, but was not affected by bicuculline methiodide. The half
      saturating concentration of bicuculline free base for blocking this purely
      voltage-gated K(+) current was 113 microM, whereas for blocking a steady Ca(2+)
      dependent K(+) current it was 36 microM. The bicuculline-sensitive voltage-gated
      K(+) current was composed of 4-AP-sensitive and 4-AP-resistant components with
      different kinetic properties. No component of the purely voltage-gated K(+)
      current was affected neither by 100 nM alpha-dendrotoxin nor by 100 nM I
      dendrotoxin. The possible K(+)-channel subtypes mediating the bicuculline
      sensitive current in MPN neurons are discussed.

PMID- 14680768
TI  - Brain areas engaged during visual judgments by involuntary access to novel
      semantic information.
AB  - Theories of visual recognition place different emphasis on the role of non
      stimulus factors. Previously, we showed that arbitrary semantic associations
      influenced visual recognition of novel objects. Here, the neural substrate of
      this effect was investigated. During a visual task, novel objects associated with
      arbitrary semantic features produced more activation in frontal and parietal
      cortex than objects associated with names. Because the task required no semantic
      retrieval, access to semantics appears to be involuntary. The brain regions
      involved have been implicated in semantic processing, thus recently acquired
      semantics activate a similar network to semantics learned over a lifetime.

PMID- 14680769
TI  - The perceived direction and speed of global motion in Glass pattern sequences.
AB  - Observers indicated the perceived direction of global motion in sequences of
      noisy Glass patterns containing real motion signals in directions that conflicted
      with the orientation of signal dipoles in the Glass patterns. Dipole orientation
      influenced the perceived direction of motion. Observers also judged the apparent
      speed of sequences of independent noiseless Glass and Glass Line patterns
      (dipoles replaced by lines). Speed was high and increased with the length of
      lines in Glass Line patterns but not with dipole separation in Glass patterns.
      When real motion signals were added to sequences of noisy Glass patterns they
      exerted an influence on apparent speed that increased with motion signal strength
      but was independent of pattern signal strength. The results suggest that pattern
      exerts a global influence on the computation of motion direction and, possibly,
      on speed.

PMID- 14680770
TI  - Suppressive effect of sustained low-contrast adaptation followed by transient
      high-contrast on peripheral target detection.
AB  - We observed that presenting a low-contrast Gabor patch (2 cpd, 5 degrees
      eccentricity, contrast=4%) for 8 s and then flashing a 20-30 ms high-contrast
      patch over it could elicit the perceptual disappearance of a subsequent low
      contrast stimulus, whereas neither low-contrast adaptation nor high-contrast
      flash alone had any considerable effect (p<0.00001). In other experiments we
      found (a) suppressive components are phase-insensitive, (b) the effect transfers
      between eyes, (c) suppression is selective for orientation, and (d) the induction
      by the transient high-contrast Gabor patch could be transferred to another
      previously adapted location up to a few degrees. Results indicate synergy between
      contrast and adaptation through a non-linear interaction between rapid gain
      adjustment to transient change and adaptation to sustained spatial patterns.
      Findings are compatible with non-local mechanisms presumably at the cortical
      level.

PMID- 14680771
TI  - Troubles with bubbles.
AB  - The bubbles method is a recently developed variant of reverse correlation methods
      that have been used in psychophysics and physiology. We show mathematically that
      for the broad and important class of noisy linear observers, the bubbles method
      recovers much less information about how observers process stimuli than reverse
      correlation does. We also show experimentally that the unusual type of noise used
      in the bubbles method can drastically change human observers' strategies in
      psychophysical tasks, which reduces the value of the information that is obtained
      from a bubbles experiment. We conclude that reverse correlation is generally
      preferable to the bubbles method in its present form, but we also give
      suggestions as to how the bubbles method could be modified to avoid the problems
      we discuss.

PMID- 14680772
TI  - No troubles with bubbles: a reply to Murray and Gold.
AB  - Murray and Gold discuss two "shortcomings" of the Bubbles method [Vision Research
      41 (2001) 2261]. The first one is theoretical: Bubbles would not fully
      characterize the LAM (Linear Amplifier Model) observer, whereas reverse
      correlation would. The second "shortcoming" is practical: the apertures that
      partly reveal information in a typical Bubbles experiment would induce atypical
      strategies in human observers, whereas the additive Gaussian white noise used by
      Murray and Gold (and others) in conjunction with reverse correlation would not.
      Here, we show that these claims are unfounded.

PMID- 14680774
TI  - No evidence for sequential effects of the interaction of stereo and motion cues
      in judgements of perceived shape.
AB  - The interaction of the depth cues of binocular disparity and motion parallax
      could potentially be used by the visual system to recover an estimate of the
      viewing distance. The present study investigated whether an interaction of stereo
      and motion has effects that persist over time to influence the perception of
      shape from stereo when the motion information is removed. Static stereoscopic
      ellipsoids were presented following the presentation of rotating stereoscopic
      ellipsoids, which were located either at the same or a different viewing
      distance. It was predicted that shape judgements for static stimuli would be
      better after presentation of a rotating stimulus at the same viewing distance,
      than after presentation of one at a different viewing distance. No such
      difference was found. It was concluded that an interaction between stereo and
      motion depth cues does not influence the perception of subsequently presented
      static objects.

PMID- 14680775
TI  - The oblique plaid effect.
AB  - Plaids are ambiguous stimuli that can be perceived either as a coherent pattern
      moving rigidly or as two gratings sliding over each other. Here we report a new
      factor that affects the relative strength of coherency versus transparency: the
      global direction of motion of the plaid. Plaids moving in oblique directions are
      perceived as sliding more frequently than plaids moving in cardinal directions.
      We term this the oblique plaid effect. There is also a difference between the two
      cardinal directions: for most observers, plaids moving in horizontal directions
      cohere more than plaids moving in vertical directions. Two measures were used to
      quantify the relative strength of coherency vs. transparency: C/[C+T] and
      RTtransp. Those measures were derived from dynamics data obtained in long
      duration trials (>1 min) where observers continually indicated their percept. The
      perception of plaids is bi-stable: over time it alternates between coherency and
      transparency, and the dynamics data reveal the relative strength of the two
      interpretations [Vision Research 43 (2003) 531]. C/[C+T] is the relative
      cumulative time spent perceiving coherency; RTtransp is the time between stimulus
      onset and the first report of transparency. The dynamics-based measures quantify
      the relative strength of coherency over a wider range of parameters than brief
      presentation 2AFC methods, and exposed an oblique plaid effect in the entire
      range tested. There was no interaction between the effect of the global direction
      of motion and the effect of gratings' orientations. Thus, the oblique plaid
      effect is due to anisotropies inherent to motion mechanisms, not a bi-product of
      orientation anisotropies. The strong effect of a plaid's global direction on its
      tendency to cohere imposes new and important constraints on models of motion
      integration and transparency. Models that rely solely on relative differences in
      directions and/or orientations in the stimulus cannot predict our results.
      Instead, models should take into account anisotropies in the neuronal populations
      that represent the coherent percept (integrated motion) and those that represent
      the transparent percept (segmented motion). Furthermore, the oblique plaid effect
      could be used to test whether neuronal populations supposed to be involved in
      plaid perception display tuning biases in favor of cardinal directions.

PMID- 14680776
TI  - A dynamic model of how feature cues guide spatial attention.
AB  - We will describe a computational model of attention which explains the guidance
      of spatial attention by feedback within a distributed network. We hypothesize
      that feedback within the ventral pathway transfers the target template from
      prefrontal areas into intermediate areas like V4. The oculomotor circuit
      consisting of FEF, LIP and superior colliculus picks up this distributed activity
      and provides a continuous spatial reentry signal from premotor cells. In order to
      test this hypothesis, we simulate two experiments that require a response given a
      color cue. The first experiment indicates a parallel feature-based enhancement
      prior to any spatial selection. If two targets are behaviorally relevant, as in
      the second experiment, experimental findings indicate that subjects split their
      attention between two locations containing the searched feature. Our simulation
      results suggest that the split in attention between two foci is a transient
      effect occurring during competition. We predict that the time after cue
      presentation determines the state of this competition and ultimately the
      distribution of attention at different locations. In addition we provide
      simulation results to explain how reentrant processing through the oculomotor
      circuit might lead to variations of the time for target detection in visual
      search.

PMID- 14680777
TI  - The representation of global spatial structure in amblyopia.
AB  - Visual processing is thought to involve initial local analyses that are
      subsequently integrated globally to derive functional representations of
      structure that extends over large areas of visual space. Amblyopia is a common
      deficit in spatial vision that could be based on either unreliable local
      estimates of image structure, irregularities in global image integration or a
      combination of errors at both these stages. The purpose of this study was to
      quantify the integration of local spatial information in amblyopia with global
      orientation discrimination and inter-ocular matching tasks. Stimuli were composed
      of pseudo-random arrays of highly visible and resolvable features (Gabor patches)
      whose local orientation and position were drawn from global distributions whose
      mean and variance statistics were systemically varied. Global orientation
      discrimination thresholds in both the amblyopic and fellow eye were elevated. The
      orientational and positional variances perceived by the amblyopic eye were
      matched by stimuli with higher variances perceived in the fellow eye. It would
      appear that amblyopes are able to integrate orientation information across visual
      space but the global representation of local structure shows greater variability
      compared to normal. It is this increased spatial uncertainty that underlies the
      spatial deficit in amblyopia.

PMID- 14680778
TI  - ERG rod a-wave in Oguchi disease.
AB  - We analyzed the change in the ERG rod a-wave waveform during the course of dark
      adaptation in two patients with Oguchi disease. Two Japanese patients showed a
      homozygous arrestin 1147delA mutation. Scotopic flash ERGs were recorded after
      different periods of dark adaptation. ERG rod a-waves were obtained after
      subtraction of the cone ERG contribution. The rod a-waves were fitted with a
      model of the rod receptor signal. The parameters, Rm(p3) (maximum a-wave
      amplitude) and S (sensitivity) were calculated. Longer periods in the dark
      produced larger rod a-wave but only to the first flash presented. The amplitude
      of the response to subsequent flashes was essentially independent of the period
      of dark adaptation. Rm(p3) increased with advance of dark adaptation. However, S
      was nearly constant. Our results suggest that the cause of delayed dark
      adaptation is not to be sought in the activation of phototransduction process or
      the regeneration of rhodopsin per se but rather in the deactivation process of
      the phototransduction cascade.

PMID- 14680779
TI  - [Digital mammography: evolution or revolution?].

PMID- 14680780
TI  - [Lymph node dissection in the surgical management of stage I endometrial
      carcinomas].
AB  - The indication and extent of lymph node dissection in the surgical management of
      endometrial cancers remain highly controversial. Randomized studies are badly
      needed but will probably lack for the next years, considering the large sample
      size required to show a small difference in survival. The trend towards a
      reduction in the routine use of external radiation therapy weakens the argument
      that radiation therapy makes adequate lymph node dissection useless. The balance
      stays between the risk for node involvement and the expected complications rate
      of the procedure. Lymph node dissection is advised whenever there is a non
      negligible risk of node metastasis in a patient at low surgical risk.

PMID- 14680781
TI  - [Epithelial inclusion cyst formation after buried vaginal mucosa. Diagnosis and
      management].
AB  - OBJECTIVES: Surgical treatment in which a vaginal mucosa island is buried leads
      to a risk of epithelial inclusion cyst formation. The aim of this study is to
      describe this complication, assess incidence, precise facilitating factors and
      discuss treatment. PATIENTS AND METHOD: This study concerned 84 patients operated
      on between January 1996 and December 1998. They were treated with modified
      vaginal wall sling procedure. Fifty women were post-menopausal and 22 had
      estrogenotherapy. All patients had post-operative surveillance. The mean post
      operative follow-up was 19 months (range: 1-68 months). Epithelial inclusion cyst
      formation diagnosis reposed exclusively on clinical assessment.Results. - Seven
      out of the 84 patients (8.3%) were diagnosed with epithelial inclusion cyst
      formation within 19 months of their operation (range: 3-34 months). Out of the
      seven patients, four were post-menopausal and three had received estrogenotherapy
      for many years. In six cases, epithelial inclusion cyst was symptomatically
      revealed by perineal pain or dysuria. These cases were successfully treated by
      cyst marsupialisation without recurrent incontinence. DISCUSSION AND CONCLUSION:
      The results of this short study show that epithelial inclusion cyst formation is
      a specific complication of surgical procedures burying a full thickness of
      vaginal mucosa and that estrogen impregnation seems to be the main facilitating
      factor. Successful treatment of symptomatic cases of epithelial inclusion cyst
      can be achieved by marsupialisation.

PMID- 14680782
TI  - [Maternal mortality: epidemiology, risk factors and evitability. About ten
      cases].
AB  - OBJECTIVES: To determine maternal mortality rate during the last decade as
      revealing the quality of obstetrical follow-up and the necessary measures to be
      taken. PATIENTS AND METHODS: A retrospective study conducted in the department of
      gynaecology in the military hospital in Tunis between 1990 and 2001, permitted to
      count 10 cases of maternal death. RESULTS: Maternal mortality rate was about
      33.72/100,000 live births. Mean age of patients was 31.2 years. Primiparity,
      multiparity, poor socio-economic conditions, high-risk pregnancies and bad follow
      up were responsible in 5, 1, 6 and 3 cases and represent the risk factors of
      mortality. All deaths occurred after delivery, with 60% before 24 h. Causes of
      death were haemorrhage in 40%, gravidic hypertension in 20%, anesthetic accidents
      in 10%, acute hepatic failure in 10%, and infection in 10%. Indirect causes are
      responsible for 20% of cases. DISCUSSION AND CONCLUSION: Deaths were judged
      evitable in 66.6% of cases, which confirms, although maternal mortality has
      diminished in the recent past, the necessity of pursuing study of risk factors
      together with study of remedies to them.

PMID- 14680783
TI  - [Preoperative endovaginal ultrasound in the assessment of myometrial invasion of
      endometrial adenocarcinoma].
AB  - OBJECTIVE: To determine, according to histological tumor grade, the reliability
      of preoperative endovaginal ultrasound in the detection of myometrial invasion in
      patients with stage I endometrial cancer. PATIENTS AND METHODS: Sixty-one
      patients with stage I endometrial carcinoma were evaluated with preoperative
      endovaginal ultrasound compared to postoperative results of pathologic
      examination, in a six-year retrospective study. RESULTS: Twenty-nine patients had
      a deep myometrial invasion (stage IC). The mean endometrial thickness was 9.5 mm
      in stage IA, 17.0 mm in stage IB and 20.0 mm in stage IC disease (P = 0.01). The
      sensitivity and the specificity of the ultrasound in the assessment of myometrial
      invasion in grade 1 tumors were 100% and 93.7%, respectively. They fell to 69.2%
      and 88.9% for high-grade tumors. The global accuracy of ultrasound was 82%.
      DISCUSSION AND CONCLUSIONS: The performance of preoperative ultrasound varies
      according to the literature. The association of morphological and morphometric
      criteria enables an increase in the sensitivity of the exam. In grade 1 tumors,
      the preoperative endovaginal ultrasound could help in identifying a group of
      patients at low risk of lymph node metastasis for which a pelvic lymphadenectomy
      would be avoidable.

PMID- 14680784
TI  - [Contribution of genotyping for fetal sex determination in maternal serum for
      preimplantation genetic diagnosis of X-linked diseases].
AB  - OBJECTIVE: Couples with a risk of transmitting X-linked diseases included in a
      preimplantation genetic diagnosis (PGD) center need early and rapid fetal sex
      determination during pregnancy in two situations. The first situation corresponds
      to control of embryo sexing after PGD, the second one being that of couples in
      PGD program having a spontaneous pregnancy. Determination of fetal sex can be
      achieved by karyotyping using invasive procedures such as chorionic villus
      sampling (CVS), amniocentesis or cordocentesis and by non-invasive procedures
      such as ultrasound (US) examination. CVS is the earliest invasive procedure for
      fetal sex determination and molecular analysis of X-linked genetic disorders
      during the first trimester but it is associated with a risk of fetal loss. US
      allows reliable fetal sex determination only during the second trimester.
      Recently, reliable non-invasive fetal sex determination was realized by using SRY
      gene amplification in maternal serum. PATIENTS AND METHODS: We report the
      prospective use of fetal sex determination in maternal serum in our PGD center.
      Management of pregnancies was performed using this non-invasive procedure in four
      cases of embryo sexing control and nine cases of spontaneous pregnancies in
      couples included in PGD program for X-linked diseases. RESULTS: Fetal sex results
      using SRY gene amplification on maternal serum were in complete concordance with
      fetal sex observed by cytogenetic analysis or US examination, as well as at
      birth. DISCUSSION AND CONCLUSION: This new strategy allowed rapid sex
      determination during the first trimester and permitted to avoid performing
      invasive procedures in nine pregnancies.

PMID- 14680785
TI  - [Isolated torsion of the Fallopian tube in a 15-year old adolescent. About one
      case].
AB  - Isolated torsion of the Fallopian tube is an uncommon event. Surgery is often
      necessary to establish the diagnosis. This report focuses on a 15-year old female
      who presented with acute pelvic pain. Pelvic ultrasound showed an adnexal mass.
      The laparoscopy performed confirmed the diagnosis of isolated tubal torsion.
      Based on this experience as well as on other similar reported cases,
      characteristics of isolated torsion of the Fallopian tube are discussed. This
      pathology should be considered in the differential diagnosis of acute pelvic pain
      in the female patient. Prompt surgical intervention may allow for preservation of
      the tube.

PMID- 14680786
TI  - [Revelation of a polymicrocystic ovary syndrome after one month's treatment by
      pulsatile GnRH in a patient presenting with functional hypothalamic amenorrhea].
AB  - Polycystic ovary syndrome (PCOS) and hypothalamic amenorrhea (HA) are the most
      frequent causes of endocrine infertility, but their association is an uncommon
      occurrence. We report the case of a 28-year old woman suffering from infertility
      and amenorrhea. Her weight was normal (BMI = 19) and she had no hirsutism. She
      self-reported food restriction and a 10 kg weight loss 5 years ago, concomitant
      with the onset of amenorrhea. At the initial evaluation, the patient was
      considered as having HA due to food restriction. At ultrasonography, ovaries were
      small and multifollicular (right and left area: 2.2 and 2.5 cm(2), respectively;
      number of cysts 2-9 mm in diameter: 15 and 12, respectively), and no stromal
      hypertrophy was noted. She has been treated for 1 month by intravenous pulsatile
      GnRH administration. Although the doses were increased from 5 to 15 microg/pulse
      every 90 min, no E2 response and no follicular development were observed.
      Hormonal re-evaluation revealed normal levels of serum LH, FSH and androgens, and
      a normal LH/FSH ratio. However, a typical aspect of PCO was found at ultrasound
      (right and left area: 6.5 and 5.5 cm(2), respectively, and more than 15 small
      cysts arranged peripherally around an increased central stroma in each ovary).
      The treatment has been then switched to hMG, using the low dose step-up regimen
      and starting with 75 U/day. In the absence of response after 2 weeks, the dose
      was increased to 112.5 U/day and a multifollicular reaction occurred, leading to
      cancellation. In conclusion, we hypothesize that this patient had a "hidden" PCOS
      when she was hypogonadotrophic and that it developed very rapidly after
      restitution of a normal gonadotropin level under exogenous GnRH. This occurred
      despite a low insulin level, showing that hyperinsulinism is not a prerequisite
      for the development of PCOS in every case.

PMID- 14680787
TI  - [Psychosomatic gynaecology or gynaecology and psychosomatics?].
AB  - Such an interrogation might well seem vain or even absurd, although one cannot
      deny that it does mean a different vision of medicine, if not an entirely
      different conception of it. Considering the sick person as a whole and not only
      the sickness of one organ means practicing a true holistic approach, far from a
      limited somatic medicine addressing the psyche only in case of failure, as a last
      resort. Rather than artificially applying to the soma some would-be psychological
      recipes, let us try and take up that bet: a simultaneous use, in time and space,
      of body and mind medicine. Psychosomatic gynaecology certainly requires will and
      training, disponibility and curiosity, but it might well be the best protection
      against boredom and routine, as well as a true source of pleasure. Can such a
      satisfying way of practicing our art be anything else than a bonus for our
      patients?

PMID- 14680788
TI  - [Non contraceptive benefits of oral contraception].
AB  - Both women and the medical profession underrate the non-contraceptive benefits of
      oral contraception, imbued as they are with its sole deleterious effects, such as
      thromboembolic ones, in particular. However, the pill is quite an efficient means
      of preventing against troubles of the menstrual cycle, with a betterment of cycle
      regularity, a diminishing of menstrual flux and a lowering of the frequency and
      the severity of primary dismenorrhoea. A review of the literature also
      demonstrates that oral contraception reduce by 40-50% the incidence of
      endometrial and ovarian cancer, inclusive of women with a previous history, or
      genetic predispositions. This effect is correlated with time of use and continues
      until 10 years or more after stopping taking the pill. Also, the positive part of
      the pill may well be considered as far as colorectal cancer is concerned, with a
      40% or so reduction in risk, by means of decreasing bile acids in the colon.
      Other benefits of oral contraception have been documented, such as prevention of
      postmenopausal osteopenia when used during perimenopause, decrease in the
      incidence of adenofibromas, uterine fibromyomas, fibrocystic mastosis and uterine
      adnexial infections, and, finally, a favourable effect on acne. Preventive action
      of the pill on rheumatoid arthritis is debatable, the current feeling being that
      it diminishes severity as well as symptomatology more than risk of occurrence.

PMID- 14680789
TI  - [How I clear the Douglas pouch from the sigmoid colon during pelvic laparoscopic
      surgeries].

PMID- 14680790
TI  - [How to perform the vaginal adnexectomy at the end of a vaginal hysterectomy].

PMID- 14680791
TI  - [How I approach the aortico-caval axis up to the subrenal veins during para
      aortic curettage].

PMID- 14680792
TI  - [Are IVF results predictable through the analysis of sperm DNA fragmentation?].

PMID- 14680793
TI  - [Physiotherapy for the post-partum period (December 2002)].

PMID- 14680794
TI  - [Fertility after hysteroscopic treatment of intra-uterine adhesions. M. Kdous et
      al. Gynecol Obstet Fertil 2003;31:422-428].

PMID- 14680795
TI  - [Fertility after hysteroscopic treatment of intra-uterine adhesions. Gynecol
      Obstet Fertil 2003;31:422-428].

PMID- 14680796
TI  - [Comparison of changes in biochemical markers of bone remodeling after 6 months
      of hormone replacement therapy with either transdermal 17 beta-estradiol or
      equine conjugated estrogen plus nomegestrol acetate. Gynecol Obstet Fertil 2003;
      31 : 434-441].

PMID- 14680797
TI  - [Should one demonize IVF? Gynecol Obstet Fertil 2003; 31 : 405-407].

PMID- 14680798
TI  - Gonadotropin-releasing hormone gene products downregulate the expression of their
      neighboring genes that encode protein tyrosine phosphatases alpha and.
AB  - It is well established that the neuropeptide gonadotropin-releasing hormone
      (GnRH) regulates the secretion of pituitary gonadotropins. Evidence also suggests
      a neuromodulatory role for GnRH, yet its mechanism is unknown. It has recently
      been shown that in the medaka genome, the GnRH II and GnRH III genes reside
      adjoining the genes encoding protein tyrosine phosphatase alpha (PTPalpha) and
      PTP, respectively. Here we isolated and characterized PTPalpha and PTP in the
      medaka, and demonstrated using an in vitro medaka whole-brain culture system that
      GnRH downregulates the PTPalpha/PTP gene expression. This finding, together with
      the fact that PTPalpha/PTP regulate neuronal excitability through interacting
      with voltage-gated potassium channel, suggests that GnRH gene products would act
      as neuromodulators via downregulating their neighboring PTPalpha/PTP genes.

PMID- 14680799
TI  - High-level expression and purification of human xylosyltransferase I in High Five
      insect cells as biochemically active form.
AB  - Human xylosyltransferase I (XT-I) catalyzes the transfer of xylose from UDP
      xylose to consensus serine residues of proteoglycan core proteins. Expression of
      a soluble form of recombinant histidine-tagged XT-I (rXT-I-HIS) was accomplished
      at a high level with High Five/pCG255-1 insect cells in suspension culture. The
      recombinant protein was purified to homogeneity by a combination of heparin
      affinity chromatography and metal (Ni(2+)) chelate affinity chromatography. Using
      the modern technique of perfusion chromatography, a rapid procedure for
      purification of the rXT-I-HIS from insect cell culture supernatant was developed.
      The purified, biologically active enzyme was homogeneous on SDS-PAGE, was
      detected with anti-XT-I-antibodies, and had the expected tryptic fragment mass
      spectrum. N-terminal amino acid sequencing demonstrated that the N-terminal
      signal sequence of the expressed protein was quantitatively cleaved. The total
      yield of the enzyme after purification was 18% and resulted in a specific XT-I
      activity of 7.9mU/mg. The K(m) of the enzyme for recombinant
      [Val(36),Val(38)](delta1),[Gly(92),Ile(94)](delta2)bikunin was 0.8microM. About
      5mg purified enzyme could be obtained from 1L cell culture supernatant. The
      availability of substantial quantities of active, homogeneous enzyme will be of
      help in future biochemical and biophysical characterization of XT-I and for the
      development of a immunological XT-I assay.

PMID- 14680801
TI  - A single point mutation resulting in an adversely reduced expression of DPM2 in
      the Lec15.1 cells.
AB  - Mammalian dolichol-phosphate-mannose (DPM) synthase consists of three subunits,
      DPM1, DPM2, and DPM3. Lec15.1 Chinese hamster ovary cells are deficient in DPM
      synthase activity. The present paper reports that DPM1 cDNA from wild type and
      Lec15.1 CHO cells were found to be identical, and transfection with CHO DPM1 cDNA
      did not reverse the Lec15.1 phenotype. Neither did a chimeric cDNA containing the
      complete hamster DPM1 open reading frame fused to the Saccharomyces cerevisiae
      DPM1 C-terminal transmembrane domain. In contrast, Lec15.1 cells were found to
      have a single point mutation G29A within the coding region of the DPM2 gene,
      resulting in a glycine to glutamic acid change in amino acid residue 10 of the
      peptide. Moreover, mutant DPM2 cDNA expressed a drastically reduced amount of
      DPM2 protein and poorly corrects the Lec15.1 cell phenotype when compared with
      wild type CHO DPM2 cDNA (G(29) form).

PMID- 14680800
TI  - Drosophila melanogaster larval hemolymph protein mapping.
AB  - With the completion of the genome sequence of Drosophila melanogaster the
      importance of constructing a proteome map is to be considered. Therefore, with
      the application of recent advances in proteomic analysis approaches, a protein
      map of D. melanogaster larvae hemolymph proteins was obtained using 2-DE in the
      range of pH 3-10. After Coomassie colloidal detection of 289 spots, a total of
      105 were excised from the gel and digested with trypsin. Identification was done
      based on a combination of MALDI-TOF/TOF MS and MS/MS spectra. The 99 proteins
      identified using this approach include a large number of metabolic enzymes,
      translational apparatus components, and structural proteins. Among these we
      emphasize the identification of proteins with molecular chaperone properties
      (heat shock proteins and PPIases) and protein spots involved in defense responses
      such as antioxidant and immunological defense mechanisms (thioredoxin,
      prophenoloxidase, and serine proteases), as well as in signal transduction
      pathways.

PMID- 14680802
TI  - Functional expression and characterization of an acidic actinoporin from sea
      anemone Sagartia rosea.
AB  - Src I is the first reported acidic actinoporin from sea anemone Sagartia rosea
      with a pI value of 4.8 and comprises 13.9% alpha-helix, 65.1% beta-sheet, and
      18.2% random coil. For structure-function studies, Src I was expressed in
      Escherichia coli as a cleavable fusion protein. Recombinant Src I exhibited
      obviously hemolytic activity, but the fusion protein Trx-Src I almost lost its
      hemolytic activity, suggesting the importance of the N-terminal amphiphilic alpha
      helix for its functional activity. The cytotoxic effects of Src I depending on
      the toxin concentration and incubation time were also observed on cultured cells.
      Among five cell lines: NIH/3T3, U251, NSCLC, BEL-7402, and BGC-823, NSCLC was the
      most sensitive cells with ID(50) 2.8 microg/ml and BGC-823 was the least
      sensitive cells with ID(50) 7.4 microg/ml. After incubated with lipid SUVs, such
      as SM-SUVs and SM/PC-SUVs, the hemolytic activity of Src I was inhibited to some
      extent. When incubated with calcein-entrapped lipid LUVs, such as SM-LUVs, SM/PC
      LUVs, and SM/PG-LUVs, Src I induced release of entrapped calcein. According to
      the interaction with lipid vesicles, we proposed that it was the membrane matrix
      made up of phospholipids, not a particular phospholipid that facilitates Src I to
      react properly.

PMID- 14680803
TI  - RNA interference for HIF-1alpha inhibits its downstream signalling and affects
      cellular proliferation.
AB  - Transcription factor HIF-1 is a key determinant of oxygen-dependent gene
      regulation. Suppression of HIF-1alpha is important for exploring HIF-1-dependent
      processes and for interfering with hypoxia-induced pathophysiological events.
      This study applied RNA-interference targeting HIF-1alpha to the human lung A549
      cell line. Transfection of HIF-1alpha-siRNA reduced HIF-1alpha synthesis as
      measured on mRNA and protein level by realtime RT-PCR, Western blot, and
      immuncytochemistry. A time kinetic for hypoxic stabilization of HIF-1alpha
      protein and its inhibition by HIF-1alpha-siRNA is included. Hypoxic induction of
      HIF-1-controlled target genes as heme oxygenase I (HO-1), phosphoglycerate kinase
      (PGK), and vascular endothelial growth factor (VEGF) was markedly attenuated by
      HIF-1alpha-siRNA treatment. Correspondingly, gene activation via hypoxia
      responsive-element, as shown by reporter gene assay, was inhibited by HIF-1alpha
      siRNA. Moreover, this approach was found to suppress the shift from from S-phase
      to G1-phase observed in A549 cells in response to hypoxia, supporting a role of
      HIF-1alpha in oxygen-dependent cell cycle regulation.

PMID- 14680804
TI  - The atypical GATA protein TRPS1 represses androgen-induced prostate-specific
      antigen expression in LNCaP prostate cancer cells.
AB  - Prostate-specific antigen (PSA) is considered as an important marker for prostate
      cancer. Regulation of PSA gene expression is mediated by androgens bound to
      androgen receptors via androgen response elements (AREs) in its promoter and far
      upstream enhancer regions. In addition, GATA proteins contribute to PSA gene
      transcription by interacting with GATA motifs present in the PSA enhancer
      sequence. The TRPS1 gene contains a single GATA zinc finger domain and not only
      binds to forward consensus GATA motifs but also to an inverse GATA motif
      overlapping the ARE III in the far upstream enhancer of the PSA gene.
      Overexpression of TRPS1 in androgen-dependent human LNCaP prostate cancer cells
      inhibited the transcription of a transiently transfected PSA enhancer/promoter
      driven luciferase reporter construct. Furthermore, overexpression of TRPS1
      reduced the androgen-induced endogenous PSA levels secreted in culture medium of
      LNCaP cells. Our results suggest a role of TRPS1 in androgen regulation of PSA
      gene expression.

PMID- 14680805
TI  - Antisense BAG-1 sensitizes HeLa cells to apoptosis by multiple pathways.
AB  - To study the mechanism of action of BAG-1 in drug-induced apoptosis, we
      constructed an antisense BAG-1 vector and established a stably transfected cell
      line from BAG-1-over-expressing HeLa cells. Reduced BAG-1 protein was confirmed
      by Western blot. Treatment of the antisense BAG-1-transfected cells with the anti
      cancer drugs staurosporine, paclitaxel, all-trans retinoic acid (ATRA), and N-(4
      hydroxyphenyl) retinamide (4-HPR) resulted in significantly enhanced apoptosis
      and reduced cell viability relative to vector-transfected cells. While the
      expression of p53 was increased, the level of Bcl-2 and Bax was decreased. Cells
      underexpressing BAG-1 had reduced cytosolic cytochrome c level. Treatment with
      staurosporine and paclitaxel resulted in increased cytochrome c release from
      mitochondria, whereas there was no change induced by treatment with ATRA and 4
      HPR. Our experiments suggest that BAG-1 inhibits anti-cancer drug-induced
      apoptosis through apoptosis regulation pathways that may involve the
      mitochondrial Bcl-2/Bax ratio, p53, and differential anti-cancer drug-mediated
      cytochrome c release.

PMID- 14680806
TI  - Accumulation of mutant myocilins in ER leads to ER stress and potential
      cytotoxicity in human trabecular meshwork cells.
AB  - MYOC encoding a 55kDa secretory glycoprotein named myocilin is closely linked to
      primary open-angle glaucoma (POAG). To understand a role played by MYOC in
      glaucoma, we examined the cellular fate of various mutant myocilins that were
      adenovirally expressed in human trabecular meshwork cells. Most myocilins with
      mutations such as G364V, Q368X, K423E, Y437H, and I477N were intrinsically
      stable, and appeared to have interactions with wild-type myocilin but not with
      stromelysin and thereby selectively inhibited the secretion of the former
      protein. The myocilins expressed were identified to be concentrated into fine
      punctate aggregates in endoplasmic reticulum, but never developed into the
      formation of aggresomes. In endoplasmic reticulum, the accumulation of the
      myocilins resulted in the upregulation of 78kDa glucose-regulated protein and
      protein disulfide isomerase. In addition, the expression of the myocilins led to
      deformed cellular morphology and diminished cell proliferation, an effect
      postulated to result in the dysfunction of trabecular cells that could be a cause
      of glaucoma. Therefore, our results support the statement that gain of function
      rather than haploinsufficiency is a critical mechanism for POAG in individuals
      with mutations on MYOC.

PMID- 14680807
TI  - Cloning and expression analysis of a Parkinson's disease gene, uch-L1, and its
      promoter in zebrafish.
AB  - Three genes, alpha-synuclein, parkin, and ubiquitin C-terminal hydrolase L1 (UCH
      L1), have been associated with inherited forms of Parkinson's disease (PD),
      although their in vivo functions have remained largely unknown. To develop an
      animal model for the molecular study of PD, we cloned zebrafish uch-L1 cDNA and
      its gene promoter. Sequence analysis revealed that the zebrafish Uch-L1 is highly
      homologous (79%) to the human UCH-L1, which is a member of the deubiquitinating
      enzymes. By whole-mount in situ hybridization, we examined the spatiotemporal
      expression of uch-L1 mRNA in developing zebrafish embryos. The uch-L1 mRNAs are
      detected in neuronal cells at the first day of embryo development. The expression
      domain of uch-L1 overlaps with that of tyrosine hydroxylase, a molecular marker
      for dopaminergic neurons, in the ventral diencephalon, an equivalent structure to
      the substantia nigra where PD progresses in human. To further analyze the tissue
      specific regulation of uch-L1 gene expression, we also tested its gene promoter
      activity and showed a preferential neuronal expression in transient transgenic
      zebrafish embryos. These results suggest that uch-L1 may have an important role
      in the development of neuronal cells in early embryos as well as in the
      degeneration and disease of neuronal cells in late adult brain.

PMID- 14680808
TI  - Structural bioinformatics study of EPSP synthase from Mycobacterium tuberculosis.
AB  - The shikimate pathway is an attractive target for herbicides and antimicrobial
      agent development because it is essential in algae, higher plants, bacteria, and
      fungi, but absent from mammals. Homologues to enzymes in the shikimate pathway
      have been identified in the genome sequence of Mycobacterium tuberculosis. Among
      them, the EPSP synthase was proposed to be present by sequence homology.
      Accordingly, in order to pave the way for structural and functional efforts
      towards anti-mycobacterial agent development, here we describe the molecular
      modeling of 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase isolated from M.
      tuberculosis that should provide a structural framework on which the design of
      specific inhibitors may be based on. Significant differences in the relative
      orientation of the domains in the two models result in "open" and "closed"
      conformations. The possible relevance of this structural transition in the ligand
      biding is discussed.

PMID- 14680809
TI  - Molecular modeling of RecX reveals its mode of interaction with RecA.
AB  - The protein RecA is involved in homologous recombination, DNA repair and also
      catalyzes DNA strand exchange. RecX gene is downstream of recA and the gene
      product RecX is supposed to be important for RecA regulation. Recombinant RecX is
      purified to homogeneity, and circular dichroism (CD) and FTIR spectroscopy show
      the protein to exist mostly in helical conformation. The fluorescence emission
      maxima of the native and the denatured protein and the steady-state fluorescence
      quenching studies with acrylamide indicate the presence of tryptophan residues
      partially exposed to the bulk solvent. Denaturation studies with urea and
      guanidine hydrochloride by use of spectroscopic methods, fluorescence, and CD
      also confirm the instability of the protein and unfolding occurs following a two
      state model. Mass spectrometry and gel permeation chromatography suggest the
      monomeric form of the protein. Molecular modeling of RecX represents the molecule
      as extended and helical bundle in conformity with the spectroscopic results. To
      understand the mechanism of RecX in the regulation of RecA the structural model
      of RecA-RecX has been discussed. In this proposed model, entry of RecX into
      hexameric RecA filament prevents binding of ssDNA and also inhibits ATPase
      activity.

PMID- 14680810
TI  - TBBz but not TBBt discriminates between two molecular forms of CK2 in vivo and
      its implications.
AB  - Two ATP-competitive inhibitors-4,5,6,7-tetrabromo-benzotriazole (TBBt) and
      4,5,6,7-tetrabromo-benzimidazole (TBBz) have been shown to decrease activity of
      CK2 holoenzyme. Surprisingly it occurs that TBBz contrary to TBBt does not
      inhibit free catalytic subunit CK2 [Formula: see text]. Both inhibitors are
      virtually inactive against RAP protein kinase. The above-mentioned protein
      kinases phosphorylate in vitro a set of acidic ribosomal P-proteins of the 60S
      ribosomal subunit. Such a modification is one of the mechanisms regulating
      translational activity of ribosomes in vivo. Application of these two very
      selective inhibitors allows us to define the role of free catalytic [Formula: see
      text] subunit of CK2 in phosphorylation of ribosomal proteins. It occurs that CK2
      [Formula: see text] but not CK2 holoenzyme is responsible for phosphorylation of
      P-proteins in vivo. Moreover, elimination of both forms of protein kinase CK2
      (hCK2 and CK2 [Formula: see text] ) activity in living cells led to dramatic loss
      of the translational activity of the ribosome.

PMID- 14680811
TI  - Activation of the human alpha1(I) collagen promoter by leptin is not mediated by
      transforming growth factor beta responsive elements.
AB  - Leptin increases human alpha1 (I) collagen mRNA and type I collagen production
      and enhances hepatic fibrosis in animal models of hepatic fibrosis. These effects
      of leptin on fibrogenesis may be mediated by TGFbeta1, since leptin increases the
      TGFbeta type II receptor and augments the effect of TGFbeta1 on collagen
      production by stellate cells. In this study, leptin increased the activity of the
      human alpha1 (I) collagen promoter in transfected stellate cells. Leptin did not
      further enhance the activation of the promoter induced by TGFbeta1. Leptin had no
      effects on the transfected TGFbeta-responsive p3TP-LUX plasmid, which contains 3
      CAGA elements that are essential and sufficient for the induction by TGFbeta.
      Leptin did not increase significantly the binding of proteins to two TGFbeta1
      responsive elements in the human alpha1 (I) collagen promoter. In conclusion,
      this study shows that leptin activates the alpha1 (I) collagen gene and that this
      effect is not mediated by TGFbeta responsive elements.

PMID- 14680812
TI  - Bovine DNase I: gene organization, mRNA expression, and changes in the
      topological distribution of the protein during apoptosis in lens epithelial
      cells.
AB  - Genomic DNA sequencing and alignment with the known DNase I mRNA showed that the
      bovine gene consists of 9 exons and that only the last 8 encode the protein,
      since initial ATG was found at exon II. RT-PCR was used to identify DNase I mRNA
      in lens epithelium in vivo and in cultured epithelial cells. We found DNase I
      transcripts having the same nucleotide sequence as the pancreas form and others
      lacking almost all exon V. The lens protein presented a slightly higher relative
      molecular weight than the pancreatic enzyme. Lens DNase I was located in
      secretory pathway organelles and excluded from the nucleus. Nevertheless, in
      apoptotic lens epithelial cells in vitro, DNase I translocated to the nucleus and
      co-localized with TUNEL positive chromatin aggregates. These results indicate
      that cells in the lens epithelium constitutively express DNase I, and suggest a
      direct involvement of this nuclease in the final phases of chromatin degradation.

PMID- 14680813
TI  - Tyrosinase scavenges tyrosyl radical.
AB  - Melanosomes scavenged tyrosyl radical that was generated by ultraviolet
      irradiation of tyrosine. Purified mushroom tyrosinase also removed tyrosyl
      radical in a dose-dependent manner. To elucidate the underlying mechanism, we
      analyzed the reaction of mushroom tyrosinase with tyrosyl radical generated by
      horseradish peroxidase and hydrogen peroxide. Resting tyrosinase, which contained
      a small amount of oxytyrosinase, did not oxidize tyrosine to DOPAchrome until
      horseradish peroxidase exhausted H(2)O(2) and thereafter the enzyme recovered its
      full activity. During the inhibition period most tyrosine was converted to
      dityrosine, suggesting that only a small amount of tyrosyl radical was enough to
      interact with a fraction of tyrosinase which was in the active oxy-form. When
      horseradish peroxidase and H(2)O(2) were added to oxytyrosinase, which was
      prepared by allowing it to turn over beforehand, DOPAchrome production was
      abolished with an accelerated consumption of H(2)O(2). Dityrosine formation was
      totally suppressed and tyrosine concentration stayed constant during the
      inhibition period with a concomitant production of O(2). The results are
      accounted for by a mechanism in which tyrosyl radical is reduced to tyrosine by
      oxytyrosinase and the resulting met-form reacts with H(2)O(2) to return to the
      oxy-form.

PMID- 14680814
TI  - Human lung fibroblasts inhibit macrophage inflammatory protein-1alpha production
      by lipopolysaccharide-stimulated macrophages.
AB  - We investigated the effect of interaction between lung fibroblasts and
      macrophages on macrophage inflammatory protein 1alpha (MIP-1alpha) production by
      macrophages. In a co-culture system consisting of WI-38 lung fibroblasts layered
      over THP-1 macrophages stimulated with lipopolysaccharide (LPS), MIP-1alpha
      production by THP-1 was significantly lower in co-culture with WI-38 than in THP
      1 alone. Treatment with conditioned medium generated from WI-38 (CM-WI-38)
      suppressed MIP-1alpha production and mRNA expression in THP-1 cells. Such
      inhibitory effect of CM-WI-38 on MIP-1alpha production was abrogated by treatment
      with indomethacin, NS-398 (a specific COX-2 inhibitor), or anti-prostaglandin
      E(2) antibody. Furthermore, even in a transwell filter system separating both
      types of cells, co-culture-induced reduction of MIP-1alpha production was
      observed. Therefore, soluble factors such as prostaglandin E(2) released from
      lung fibroblasts are responsible for the co-culture-induced inhibition of
      macrophage-derived MIP-1alpha production, suggesting that immune and inflammatory
      cell interactions can contribute to the modulatory mechanisms involved in the
      regulation of the inflammatory or fibrotic process.

PMID- 14680815
TI  - Both N- and C-terminal transactivation functions of DNA-bound ERalpha are blocked
      by a novel synthetic estrogen ligand.
AB  - Estrogen receptors (ERs) play a central role in the diverse actions of estrogen.
      A number of synthetic ER ligands have been generated that can modulate various ER
      functions. Here we show that TAS-108, representing a novel class of synthetic ER
      ligands, blocked both ER transactivation functions without inhibiting DNA-binding
      activity. A transient expression assay showed that similar to ICI182,780, TAS-108
      exhibited pure antagonistic activity as it blocked both the N-terminal AF-1 and C
      terminal AF-2 transactivation functions. However, unlike ICI182,780, TAS-108
      promoted the recruitment of the SMRT co-repressor that abolished ER
      transactivation function without inhibition of the ability of ERalpha to bind to
      its target DNA. Both TAS-108 and ICI182,780 acted as antagonists for the
      transactivation functions of the D351Y mutant, derived from tamoxifen-resistant
      breast cancer cells, while estrogen and known selective estrogen receptor
      modulators (SERMs), 4-OH tamoxifen and raloxifene, stimulated D351Y-mediated
      transcription. Thus, our findings indicated that TAS-108 acts as a novel estrogen
      antagonist that recruits co-repressors to ERs without AF-1 activation or
      prevention of DNA binding. Therefore, TAS-108 may be effective against tamoxifen
      resistant breast cancer via a different mechanism than that for ICI182,780.

PMID- 14680816
TI  - Reconstitution of vesicular transport to Rab11-positive recycling endosomes in
      vitro.
AB  - Rab GTPases are key regulators of vesicular protein transport in both the
      endocytic and exocytic pathways. In endocytosis and recycling, Rab11 plays a role
      in receptor recycling to plasma membrane via the pericentriolar recycling
      compartment. However, little is known about the molecular requirements and
      partners that promote transport through Rab11-positive recycling endosomes. Here,
      we report a novel approach to reconstitute transport to immunoabsorbed recycling
      endosomes in vitro. We show that transport is temperature-, energy-, and time
      dependent and requires the presence of Rab proteins, as it is inhibited by the
      Rab-interacting protein Rab GDP-dissociation inhibitor that removes Rab proteins
      from the membrane. Cytochalasin D, a drug that blocks actin polymerization,
      inhibits the in vitro assay, suggesting that transport to recycling endosomes
      depends on an intact actin cytoskeleton. Using an affinity chromatography
      approach we show the identification of Rab11-interacting proteins including actin
      that stimulate transport to recycling endosomes in vitro.

PMID- 14680817
TI  - Tyrosine phosphorylation of the Rab24 GTPase in cultured mammalian cells.
AB  - Several members of the large family of Rab GTPases have been shown to function in
      vesicular trafficking in mammalian cells. However, the exact role of Rab24
      remains poorly defined. Rab24 differs from other Rab proteins in that it has a
      low intrinsic GTPase activity and is not efficiently prenylated. Here we report
      an additional unique property of Rab24; i.e., the protein can undergo tyrosine
      phosphorylation when overexpressed in cultured cells. Immunoblot analyses with
      specific anti-phosphotyrosine monoclonal antibodies revealed the presence of
      phosphotyrosine (pTyr) on myc-Rab24 in whole cell lysates and immunoprecipitated
      samples. No pTyr was detected on other overexpressed myc-tagged GTPases (H-Ras,
      Rab1b, Rab6, Rab11 or Rab13). Comparisons of myc-Rab24 in the soluble and
      particulate fractions from HEK293 and HEp-2 cells indicated that the cytosolic
      pool of Rab24 was more heavily phosphorylated than the membrane pool. Treatment
      of transfected cells with the broad-spectrum tyrosine kinase inhibitor,
      genistein, as well as the specific Src-family kinase inhibitor, PP2, eliminated
      the pTyr signal from Rab24. In contrast the receptor tyrosine kinase inhibitor,
      tyrphostin A25, had no effect. Tyrosine phosphorylation of Rab24 was reduced by
      alanine substitution of two unique tyrosines, one found in a strong consensus
      phosphorylation motif (Y [Formula: see text] ) in the hypervariable domain (Y172)
      and the other falling within the GXXXGK(S/T) motif known as the P-loop (Y17). The
      latter region is known to influence GTP hydrolysis in Rab proteins, so the
      phosphorylation of Y17 could contribute to the low intrinsic GTPase activity of
      Rab24. This is the first report of tyrosine phosphorylation in any member of the
      Ras superfamily and it raises the possibility that this type of modification
      could influence Rab24 targeting and interactions with effector protein complexes.

PMID- 14680819
TI  - Analysis of extrachromosomal homologous recombination in cultured silkworm cells.
AB  - Double-strand breaks (DSBs) are potentially lethal lesions causing the loss of
      chromosomal information. Eukaryotic cells have evolved the error-free repair
      systems of DSBs by homologous recombination (HR) through gene conversion with or
      without crossing over. In this study, we have developed a rapid assay system for
      extrachromosomal HR events in the cultured silkworm BmN4 cells. When HR occurs
      within the disrupted luciferase gene, an enzymatically active luciferase is
      restored and expressed. Our results strongly suggest that error-prone single
      strand annealing (SSA) accounts for the majority of extrachromosomal
      recombination processes in the cells. However, upon the substrates which cannot
      be repaired through SSA, DSBs were efficiently repaired though gene conversion.
      The rapid and sensitive HR assay system developed in the present study is
      expected to be a powerful tool for the identification and analysis of HR-related
      genes in the silkworm.

PMID- 14680818
TI  - Tuberous sclerosis genes regulate cellular 14-3-3 protein levels.
AB  - The genes TSC1, encoding hamartin, and TSC2, encoding tuberin are responsible for
      tuberous sclerosis. This autosomal dominant tumor suppressor gene syndrome
      affects about 1 in 6000 individuals. A variety of tumors characteristically occur
      in different organs of tuberous sclerosis patients and are believed to result
      from defects in cell cycle/cell size control. We performed a proteomics approach
      of two-dimensional gel electrophoresis with subsequent mass spectrometrical
      identification of protein spots after ectopic overexpression of human TSC1 or
      TSC2. We found the cellular levels of four isoforms of the 14-3-3 protein family,
      14-3-3 gamma, 14-3-3, 14-3-3 sigma, and 14-3-3 zeta, to be regulated by the two
      tuberous sclerosis gene products. In the same experiments the protein levels of
      keratin 7, capZ alpha-1 subunit, ezrin, and nedasin were not affected by ectopic
      TSC1 or TSC2. Western blot analyses confirmed the deregulation of 14-3-3 proteins
      upon ectopic overexpression of TSC1 and TSC2. A TSC1 mutant not encoding the
      transmembrane domain and the tuberin-binding domain but harbouring most of the
      coiled-coil region and the ERM protein interaction domain of hamartin did not
      affect 14-3-3 protein levels. The here presented findings suggest that
      deregulation of 14-3-3 protein amounts might contribute to the development of
      tumors in tuberous sclerosis patients. These data provide important new insights
      into the molecular development of this disease especially since both, the TSC
      genes and the 14-3-3 proteins, are known to be involved in mammalian cell cycle
      control.

PMID- 14680820
TI  - Differential Ras signaling via the antigen receptor and IL-2 receptor in primary
      T lymphocytes.
AB  - Ras can become activated via multiple distinct receptors in T lymphocytes.
      However, mechanistic studies of Ras signaling in normal T cells have been
      hampered by the lack of an efficient technology for gene transfer into resting
      post-thymic cells. We have overcome this limitation by utilizing adenoviral
      transduction of T cells from Coxsackie/adenovirus receptor transgenic mice.
      Unexpectedly, dominant negative Ras17N blocked activation of Ras and ERK in
      response to IL-2R engagement but not TCR/CD3 ligation. However, TCR-induced ERK
      activation was suppressed by inhibitors of PKC and PLC-gamma. This first
      biochemical study of DN Ras in normal quiescent T cells reveals a striking
      contrast in Ras signaling via two receptors, and suggests that the principal
      mechanism of TCR-induced Ras activation in normal T cells may be distinct from
      that utilized in T-lineage tumor cell lines.

PMID- 14680821
TI  - Role of follitropin receptor signaling in nuclear protein transitions and
      chromatin condensation during spermatogenesis.
AB  - Follitropin receptor (FSHR) in testicular Sertoli cells mediates signaling by
      pituitary follitropin (FSH) promoting intercellular communication with germ cells
      for normal spermatogenesis. Using receptor knockout mice we examined changes in
      sperm nucleoproteins and chromatin architecture. The expressions of transition
      proteins 1/2 (TP1/2) and protamine-2 (PRM-2) were greatly diminished at 21 days,
      but returned to normal at 35 days and 3 months after birth. However, protein
      components in chromatin were quite different. Western blots detected a reduction
      in PRM1/2 and prolonged retention of mono-ubiquitinated histone 2A (uH2A) in the
      epididymal sperm from adult mutants. Two forms of mono- and poly-uH2A were
      present in sonication-resistant testicular spermatids in normal mice, whereas
      only an elevated mono-uH2A was detectable in mutants. Decrease in PRM1/2 and
      retention of mono-uH2A was coincident with reduction in TP1/2 in premature
      spermatids. Thus lack of FSHR signaling impairs expression of TP1/2 and PRM-2 at
      an early stage of post-natal development causing delayed spermatogenesis. In the
      adult, absence of FSHR signaling prolongs retention of mono-uH2A, leading to
      impair transition of basic nucleoproteins and chromatin remodeling during mouse
      spermatogenesis.

PMID- 14680822
TI  - Transcriptional regulation of the murine brca2 gene by CREB/ATF transcription
      factors.
AB  - The brca2 gene encodes a nuclear protein which is mainly involved in DNA repair
      and, when mutated, is responsible for some of the hereditary breast cancers.
      However, brca2 expression is also deregulated in sporadic breast tumors. In the
      mouse brca2 gene we had earlier identified a region of 148bp upstream of the
      transcription start site sufficient to activate its expression. In the present
      report, we show that the -92 to -40bp region is essential for the transcription
      of brca2 in murine mammary cells and that this nucleotide sequence contains one
      putative CREB/ATF consensus site (cAMP responsive element: CRE). We demonstrated
      that the mutation of this binding site led to a highly significant reduction of
      the mouse brca2 transcription, and that CREB, CREM, and/or ATF-1 functionally
      bound to and regulated this promoter. Therefore, the regulation of the promoter
      of the mouse brca2 gene is driven by this family of transcription factors.

PMID- 14680823
TI  - The IspA protease's involvement in the regulation of the sporulation process of
      Bacillus thuringiensis is revealed by proteomic analysis.
AB  - We have observed that the process of sporulation of the ispA-deficient mutant was
      delayed under phase-contrast microscopy. The protein profiles of the ispA
      deficient mutant have been analyzed using two-dimensional gel electrophoresis.
      The results of a proteomic analysis using MALDI-TOF MS indicated that a
      sporulation-associated protein, pro- [Formula: see text], was upregulated, while
      two other sporulation-associated proteins, SpoVD and SpoVR, were downregulated in
      the ispA-deficient mutant. It has been known that pro- [Formula: see text] is a
      precursor of [Formula: see text] and is required for gene expression related to
      the late stage of sporulation. Moreover, SpoVD and SpoVR are known to be involved
      in the formation of the spore cortex. Based on these observations, we propose
      that the delay in the sporulation process observed in the ispA-deficient mutant
      may be due to a failure of [Formula: see text] to signal sporulation. This
      phenomenon may be further enhanced by insufficient amount of SpoVD and SpoVR for
      cortex formation. In this study, we have revealed for the first time a possible
      pathway for the regulation of sporulation-associated proteins via IspA.

PMID- 14680824
TI  - Glucocorticoid response and promoter occupancy of the mouse LXRalpha gene.
AB  - The liver X receptors alpha and beta (LXRalpha and LXRbeta) are members of the
      nuclear receptor superfamily of proteins which are highly expressed in
      metabolically active tissues. They regulate gene expression of critical genes
      involved in cholesterol catabolism and transport, lipid and triglyceride
      biosynthesis, and carbohydrate metabolism in response to distinct oxysterol
      intermediates in the cholesterol metabolic pathway. Several LXR target genes have
      been identified, but there is limited information on how expression of the LXRs
      themselves is controlled. In this study we have characterized the upstream
      flanking region of the mouse LXRalpha gene. Transient transfections show that the
      LXRalpha promoter is able to drive transcription of a luciferase reporter gene,
      however, the transcriptional potential of the promoter in the cell lines used was
      low. The -2143 to -1513 region of the promoter mediates repression of reporter
      gene activity in all cells analyzed and multiple DNA-protein interactions were
      detected in this region by DNase I footprinting. The Zta, Ets, and Hes1
      transcription factors were all shown to mediate alterations in reporter gene
      activity driven by LXRalpha promoter deletion constructs. These factors have been
      linked to cell cycle and differentiation processes suggesting that expression of
      LXRalpha might be under control of signalling mechanisms regulating cell
      proliferation. Several putative binding sites of the glucocorticoid receptor (GR)
      were identified in the LXRalpha promoter and transient cotransfections of the GR
      and LXRalpha promoter deletion constructs induced reporter gene activity.
      Addition of dexamethasone, a GR agonist, abolished this effect suggesting cross
      talk between GR and LXR signalling.

PMID- 14680825
TI  - Fibroblasts regulate contractile force independent of MMP activity in 3D
      collagen.
AB  - The extracellular matrix not only provides a structural scaffold for cells to
      inhabit but also forms a conduit by which mechanical information may be
      transmitted. Fibroblasts undergo a variety of changes when activated, including
      upregulating matrix metalloproteinase (MMP) activity and establishing a smooth
      muscle-like contractile apparatus. The relationship between MMP activity and
      matrix contraction has yet to be established. Here we report that inhibition of
      MMP activity correlates with a significant reduction in collagen gel contraction,
      however, force development does not change respective to MMP activity. These
      results suggest cellular controls of contractile forces are independent of MMP
      activity. Our results also raise the possibility that the material properties of
      the matrix dynamically change during remodeling.

PMID- 14680826
TI  - Stability and apoptotic activity of recombinant human cytochrome c.
AB  - An efficient system for producing human cytochrome c variants is important to
      help us understand the roles of this protein in biological processes relevant to
      human diseases including apoptosis and oxidative stress. Here, we describe an
      Escherichia coli expression system for producing recombinant human cytochrome c.
      We also characterize the structure, stability, and function of the protein and
      show its utility for studying apoptosis. Yields of greater than 8 mg of pure
      protein per liter culture were attained. Circular dichroism spectropolarimetry
      studies show that the secondary and tertiary structures of the human protein are
      nearly identical to those of the horse protein, but the human protein is more
      stable than other eukaryotic cytochromes c. Furthermore, recombinant human
      cytochrome c is capable of inducing caspase-3 activity in a cell-free caspase
      activation assay. We use data from this assay along with data from the literature
      to define the apaf-1 binding site on human cytochrome c.

PMID- 14680827
TI  - Molecular cloning and expression of a smooth muscle-specific gene SM22alpha in
      zebrafish.
AB  - SM22alpha is a kind of 22-kDa protein which is exclusively expressed in smooth
      muscle containing tissues of the vertebrates. Here we report molecular cloning of
      a novel zebrafish SM22alpha gene. The full length of zebrafish SM22alpha cDNA is
      1296bp and it encodes a polypeptide of 201 amino acids which shares 69.2%, 69.7%,
      69.2%, 67.2%, and 61.2% overall identity with human, mouse, rat, chicken, and
      bovine SM22alpha, respectively. Characterization of zebrafish SM22alpha genomic
      sequence reveals that it spans 7.7kb and contains five exons and four introns.
      The expression pattern of SM22alpha in zebrafish embryonic development is studied
      by whole-mount in situ hybridization. Strong expression is observed in vascular,
      gut, swim bladder, branchial arches, and fin epidermis. Furthermore, we carry out
      gene knock-down by antisense morpholino oligonucleotide, which results in
      disappearance of yolk extension, caudal fin aberrance, and deficiency of
      circulation system in zebrafish embryo. Cross-section of SM22alpha-deficient
      embryo suggests that SM22alpha may play roles in smooth muscle cell morphology
      transform.

PMID- 14680828
TI  - Identification and characterization of mouse GTPBP3 gene encoding a mitochondrial
      GTP-binding protein involved in tRNA modification.
AB  - We report here the identification and characterization of mouse GTPBP3 encoding a
      mitochondrial GTPase. A full-length GTPBP3 cDNA has been isolated and the genomic
      organization of GTPBP3 has been elucidated. The mouse GTPBP3 gene containing 9
      exons encodes a 486 residue protein with a strong homology to the GTPBP3-like
      proteins of bacteria, yeast, and other homologs, related to tRNA modification.
      The mouse GTPBP3 is ubiquitously expressed in various tissues, but abundantly in
      tissues with high metabolic rates including heart, liver, and brain.
      Surprisingly, this gene, unlike its human homolog, exhibited a low expression in
      skeletal muscle. Furthermore, immunofluorescence analysis of NIH3T3 cells
      expressing GTPBP3-GFP fusion protein demonstrated that the mouse Gtpbp3 localizes
      in mitochondrion. These observations suggest that the mouse Gtpbp3 is an
      evolutionarily conserved mitochondrial GTP-binding protein involved in the tRNA
      modification. Thus, it may modulate the translational efficiency and accuracy of
      codon-anticodon base pairings on the decoding region of mitochondrial ribosomes.

PMID- 14680830
TI  - cDNA cloning, expression, and mutagenesis of a PR-10 protein SPE-16 from the
      seeds of Pachyrrhizus erosus.
AB  - SPE-16 is a new 16kDa protein that has been purified from the seeds of
      Pachyrrhizus erosus. It's N-terminal amino acid sequence shows significant
      sequence homology to pathogenesis-related class 10 proteins. cDNA encoding 150
      amino acids was cloned by RT-PCR and the gene sequence proved SPE-16 to be a new
      member of PR-10 family. The cDNA was cloned into pET15b plasmid and expressed in
      Escherichia coli. The bacterially expressed SPE-16 also demonstrated ribonuclease
      like activity in vitro. Site-directed mutation of three conserved amino acids
      E95A, E147A, Y150A, and a P-loop truncated form were constructed and their
      different effects on ribonuclease activities were observed. SPE-16 is also able
      to bind the fluorescent probe 8-anilino-1-naphthalenesulfonate (ANS) in the
      native state. The ANS anion is a much-utilized "hydrophobic probe" for proteins.
      This binding activity indicated another biological function of SPE-16.

PMID- 14680829
TI  - Analysis of a substrate specificity switch residue of cephalosporin acylase.
AB  - Residue Phe375 of cephalosporin acylase has been identified as one of the
      residues that is involved in substrate specificity. A complete mutational
      analysis was performed by substituting Phe375 with the 19 other amino acids and
      characterising all purified mutant enzymes. Several mutations cause a substrate
      specificity shift from the preferred substrate of the enzyme, glutaryl-7-ACA,
      towards the desired substrate, adipyl-7-ADCA. The catalytic efficiency (
      [Formula: see text] (cat)/ [Formula: see text] (m)) of mutant SY-77(F375C)
      towards adipyl-7-ADCA was increased 6-fold with respect to the wild-type enzyme,
      due to a strong decrease of [Formula: see text] (m). The [Formula: see text]
      (cat) of mutant SY-77(F375H) towards adipyl-7-ADCA was increased 2.4-fold. The
      mutational effects point at two possible mechanisms by which residue 375
      accommodates the long side chain of adipyl-7-ADCA, either by a widening of a
      hydrophobic ring-like structure that positions the aliphatic part of the side
      chain of the substrate, or by hydrogen bonding to the carboxylate head of the
      side chain.

PMID- 14680831
TI  - Crystal structure of human PNP complexed with guanine.
AB  - Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N
      ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for
      inhibitor development aiming at T-cell immune response modulation and has been
      submitted to extensive structure-based drug design. More recently, the 3-D
      structure of human PNP has been refined to 2.3A resolution, which allowed a
      redefinition of the residues involved in the substrate-binding sites and provided
      a more reliable model for structure-based design of inhibitors. This work reports
      crystallographic study of the complex of Human PNP:guanine (HsPNP:Gua) solved at
      2.7A resolution using synchrotron radiation. Analysis of the structural
      differences among the HsPNP:Gua complex, PNP apoenzyme, and HsPNP:immucillin-H
      provides explanation for inhibitor binding, refines the purine-binding site, and
      can be used for future inhibitor design.

PMID- 14680832
TI  - Function of fibrinogen gamma-chain dodecapeptide-conjugated latex beads under
      flow.
AB  - In order to perform a fundamental study of platelet substitutes, novel particles
      that bound to activated platelets were prepared using two oligopeptides
      conjugated to latex beads. The oligopeptides were CHHLGGAKQAGDV (H12), which is a
      fibrinogen gamma-chain carboxy-terminal sequence (gamma 400-411), and CGGRGDF
      (RGD), which contains a fibrinogen alpha-chain sequence (alpha 95-98 RGDF). Both
      peptides contained an additional amino-terminal cysteine to enable conjugation.
      Human serum albumin was adsorbed onto the surface of latex beads (average
      diameter 1microm) and pyridyldisulfide groups were chemically introduced into the
      adsorbed protein. H12 or RGD peptides were then chemically linked to the modified
      surface protein via disulfide linkages. H12- or RGD-conjugated latex beads
      prepared in this way enhanced the in vitro thrombus formation of activated
      platelets on collagen-immobilized plates under flowing thrombocytopenic-imitation
      blood. Based on the result of flow cytometric analyses of agglutination, PAC-1
      binding, antiP-selectin antibody binding, and annexin V binding, the H12
      conjugated latex beads showed minimal interaction with non-activated platelets.
      These results indicate the excellent potential of H12-conjugated particles as a
      candidate for a platelet substitute.

PMID- 14680833
TI  - Suppression of the dual-specificity phosphatase MKP-1 enhances HIF-1 trans
      activation and increases expression of EPO.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a phosphorylated protein and its
      phosphorylation is involved in HIF-1alpha subunit stabilization as well as in the
      regulation of HIF-1 transcriptional activity. In a variety of cell lines, the
      phosphorylation of HIF-1alpha is dependent on ERK or p38, two members of the
      mitogen-activated protein kinase (MAPK) superfamily. In addition, active MAPK
      could be inactivated through dephosphorylation by mitogen-activated protein
      kinase phosphatase-1 (MKP-1). MKP-1 has been identified as a hypoxia responsive
      gene, but its role in the response of cells to hypoxia is poorly understood. Here
      we found that hypoxia induces MKP-1 expression in human hepatoma cells HepG2 in a
      time-dependent manner. Inhibition of MKP-1 expression using siRNA technique could
      enhance HIF-1alpha phosphorylation, accompanied by an increase in
      transcriptionally active HIF-1 as well as a rise in the levels of HIF-1-induced
      erythropoietin expression.

PMID- 14680834
TI  - Inhibition of P-selectin-mediated cell adhesion by a sulfated derivative of
      sialic acid.
AB  - P-selectin, a carbohydrate-binding cell adhesion molecule expressed on activated
      endothelial cells and platelets, plays a key role in the recruitment of
      leukocytes to inflammatory and hemorrhagic sites. It simultaneously recognizes a
      sialic acid-containing carbohydrate chain and the sulfated tyrosine residues of a
      specific counter-receptor expressed on the leukocyte surface. We examined the
      inhibitory effects of a synthetic sulfated derivative of sialic acid (NMSO3) on P
      selectin-mediated cell adhesion and found the following: (1) P-selectin/IgG
      chimera bound to immobilized NMSO3. (2) The binding of P-selectin/IgG chimera to
      purified P-selectin glycoprotein ligand-1 was inhibited by soluble NMSO3. (3) The
      adhesion of HL60 cells to P-selectin-expressing CHO cells was inhibited by NMSO3.
      (4) NMSO3 inhibited P-selectin-induced tumor necrosis factor-alpha production in
      monocytes and activated platelet-induced generation of reactive oxygen species in
      neutrophils. In conclusion, NMSO3 acts as a specific inhibitor for P-selectin
      mediated cell adhesion and for adhesion-dependent leukocyte activation.

PMID- 14680835
TI  - Enhanced expression of neuronal nitric oxide synthase in islets of exercise
      trained rats.
AB  - It is well known that glucose-stimulated insulin secretion (GSIS) decreases after
      exercise training. In the present study, we investigated the effects of exercise
      training (9 weeks of running) on the activity of glucokinase (GK), the production
      of nitric oxide (NO), and the protein expressions of both glucose transporter-2
      (GLUT-2) and NO synthase (NOS) in rat pancreatic islets. Exercise training
      significantly reduced GSIS, with decreases in GK activity and GLUT-2 protein
      expression. The NO releases and cGMP contents were higher in the islets of
      trained rats than in those of control rats. Exercise training enhanced cNOS
      activity, the protein expression of both neuronal nitric oxide synthase (nNOS)
      and calmodulin, and NADPH-cytochrome c reductase activity in the homogenates of
      islets. Thus, exercise training-induced reduction of GSIS would result from, at
      least in part, decreases in both glucose entry and the first step in glycolytic
      utilization of glucose. Moreover, exercise training could enhance the protein
      expression of nNOS, which in turn enhances two catalytic activities of nNOS, an
      NO production and a cytochrome c reductase activity.

PMID- 14680836
TI  - Canstatin-N fragment inhibits in vitro endothelial cell proliferation and
      suppresses in vivo tumor growth.
AB  - Type IV collagen is one of the components of vascular basement involved in
      regulation of angiogenesis. Canstatin, the non-collagenous 1 (NC1) domain of
      alpha2 chain of type IV collagen, was identified as an inhibitor of angiogenesis
      and tumor growth by Kamphaus et al. Our previous studies showed that canstatin-N,
      the N-terminal 1-89 amino acid fragment of canstatin, inhibited the
      neovascularization in a dose-dependent manner as tested by CAM assay. In the
      present study, we demonstrate that canstatin-N produced in Escherichia coli
      specifically inhibited in vitro the proliferation of human umbilical vein
      endothelial cells (ECV304) and significantly induced apoptosis. The apoptosis
      inducing activity of canstatin-N was much stronger than that of canstatin,
      indicating that the apoptosis-inducing activity of canstatin is likely located
      within its N-terminal 1-89 amino acid fragment. Canstatin-N also suppressed in
      vivo growth of B(16) murine melanoma in BALB/c mice at a dosage of 10mg/kg/day.
      These results suggest that canstatin-N is a useful candidate molecule for
      inhibition of tumor growth.

PMID- 14680837
TI  - Hepatitis B virus X protein does not influence essential steps of nucleotide
      excision repair effected by human liver extracts.
AB  - The X protein (HBx) of hepatitis B virus (HBV) is thought to compromise TFIIH
      function during hepatocyte nucleotide excision repair (NER) to cause the
      accumulation of hepatocarcinogenic mutations. The TFIIH holoenzyme, including XPB
      and XPD helicases, is absolutely required for transcription coupled (TCR) as well
      as global genome (GGR) NER pathways. Using an assay in which GGR carried out by
      extracts of foetal hepatocytes is reconstituted, we found that incisions
      [Formula: see text] and [Formula: see text] to a defined cisplatin DNA lesion
      occurred normally in the presence of functional recombinant HBx. Moreover, HBx
      did not significantly impair synthesis of the repair patch that completes the NER
      pathway. These data indicate that HBx does not directly interrupt the function of
      TFIIH during GGR and suggest that any HBx-mediated inhibitory effect on TFIIH is
      a transcription-coupled event.

PMID- 14680838
TI  - Tryptophan modification by 2-hydroxy-5-nitrobenzyl bromide studied by MALDI-TOF
      mass spectrometry.
AB  - The reaction with 2-hydroxy-5-nitrobenzyl bromide (HNB) is a common covalent
      modification of tryptophan. It results in several products which have been
      described by classical physico-chemical methods. To improve the understanding of
      the HNB-modified tryptophan structure, we synthesized a model peptide containing
      one tryptophan only, modified it by HNB, and analyzed the product by MALDI-TOF
      mass spectrometry. Surprisingly, several multi-modified products (up to 5 HNB
      moieties per one tryptophan) were identified. the influence of HNB concentration
      and pH on the degree of modification was also analyzed. In addition, a splitting
      of modified tryptophan peaks in MALDI-TOF spectrum was described; most probably,
      this effect is a common MALDI artifact of nitro-aromatic compounds which
      facilitates the identification of HNB-modified tryptophan by MALDI-TOF MS
      significantly.

PMID- 14680839
TI  - The divergent 5' ends of DPM2 mRNAs originate from the alternative splicing of
      two adjacent introns: characterization of the hamster DPM2 gene.
AB  - Mammalian dolichol-phosphate-mannose (DPM) synthase has three subunits, DPM1,
      DPM2, and DPM3. In this report, an analysis of the gene and cDNAs of hamster DPM2
      is presented. The CHO DPM2 gene has two special features. First, the initiation
      codon ATG is separated from the remainder of the coding region by intron
      sequences. Second, within these intron sequences the DPM2 gene contains an
      adjacent 3' splice site (acceptor) and a 5' splice site (donor), suggestive of a
      deleted exon between the first and second codons. In fact, these sites overlap by
      four nucleotides (nt) of AGGT. Splicing intermediates using both of these
      alternative splice sites were observed. This latter feature appears unique and is
      particularly unusual considering the relatively small size of the gene (2.7 kb)
      and of introns a (123 bp) and b (152 bp).

PMID- 14680840
TI  - A system using convertible vectors for screening soluble recombinant proteins
      produced in Escherichia coli from randomly fragmented cDNAs.
AB  - Protein insolubility is a major problem when producing recombinant proteins
      (e.g., to be used as antigens) from large cDNAs in Escherichia coli. Here, we
      describe a system using three convertible plasmid vectors to screen for soluble
      proteins produced in E. coli. This system experimentally identified any random
      cDNA fragments producing soluble protein domains. Shotgun fragments introduced
      into any of our three plasmids, which contain Gateway recombination sites, fused
      in-frame to the ORF of the protein tag. These plasmids produced N-terminal GST-
      and C-terminal three-frame-adaptive FLAG-tagged proteins, kanamycin-resistant
      gene-tagged proteins (which were pre-selected for in-frame fused cDNAs), or GFP
      tagged fusion proteins. The latter is useful as a fluorescence indicator of
      protein folding. The Gateway recombination sites promote smooth conversion for
      enrichment of in-frame clones and facilitate both protein solubility assays and
      final production of proteins without the C-terminal tag. This high-throughput
      screening method is particularly useful for procedures that require the handling
      of many cDNAs in parallel.

PMID- 14680841
TI  - Mouse MafA, homologue of zebrafish somite Maf 1, contributes to the specific
      transcriptional activity through the insulin promoter.
AB  - Large Maf transcription factors, which are members of the basic leucine zipper (b
      Zip) superfamily, have been reported to be involved in embryonic development and
      cell differentiation. Previously, we isolated a novel zebrafish large Maf cDNA,
      somite Maf1 (SMaf1), which possesses transactivational activity within its N
      terminus domain. To elucidate SMaf1 function in mammals, we tried to isolate the
      mouse homologue of zebrafish SMaf1. We isolated the mouse homologue of zebrafish
      SMaf1, which is the same molecule as the recently reported MafA. MafA mRNA was
      detected in formed somites, head neural tube, and liver cells in the embryos. In
      the adult mouse, MafA transcript was amplified in the brain, lung, spleen, and
      kidney by RT-PCR. MafA mRNA was also detectable in beta-cell line. Next, we
      analyzed the transcriptional activity of MafA using rat insulin promoters I and
      II (RIPI and II), since a part of RIP sequence was similar to the Maf recognition
      element (MARE) and MafA was expressed in pancreatic beta cells. MafA was able to
      activate transcription from RIPII, but not RIPI, in a dose dependent manner and
      the activity was dependent on RIPE3b/C1 sequences. In addition, the amount of
      MafA protein was regulated by glucose concentration. These results indicate that
      MafA is the homologue of zebrafish SMaf1 and acts as a transcriptional activator
      of the insulin gene promoter through the RIPE3b element.

PMID- 14680842
TI  - Suppression of cytochrome c release and apoptosis in testes with heat stress by
      minocycline.
AB  - Spermatogenic cells are susceptible to heat stress and undergo apoptosis.
      Although a variety of factors appear to be involved in the apoptotic process, the
      nature of the intracellular signaling pathway is ambiguous. To clarify the
      process, we chose a simple model in which testes of mice were exposed to mild
      heating by immersion in hot water at 42 degrees C for 15 min. In situ DNA
      fragmentation was detected by a TUNEL method. The release of cytochrome c into
      the cytoplasm was observed by Western blotting both in heat-treated testis and in
      isolated spermatogenic cells that had been incubated at 42 degrees C for 1h, but
      not in Sertoli cells. Minocycline, a semisynthetic tetracycline, is known to
      reach the brain by permeating the blood-brain barrier and suppresses apoptosis in
      neuronal cells. Since the testis also has a similar barrier, minocycline was
      examined as a possible agent to inhibit heat stress-induced apoptosis. The
      results indicate that minocycline suppressed the release of cytochrome c from
      mitochondria both in vivo and in vitro and significantly decreased the number of
      TUNEL-positive cells. These findings suggest that heat stress of testes triggers
      the release of cytochrome c from mitochondria in spermatogenic cells, leading to
      the activation of an apoptotic pathway.

PMID- 14680843
TI  - Identification of a five-pass transmembrane protein family localizing in the
      Golgi apparatus and the ER.
AB  - A family of five-pass transmembrane proteins (FinGERs) were identified from the
      protein sequence database. The family includes yeast Yip1p, Yip4p, Yip5p, and
      Yif1p, and also their plant, insects, nematode, and mammalian homologues,
      suggesting their conserved function in a broad range of species. Eight family
      members were found in human. Multiple sequence alignment revealed three regions
      conserved among all family members. All of the human family members were
      expressed widely in various tissues. The human proteins were localized in and
      around the Golgi apparatus and may also be in the ER to some extent. The Golgi
      apparatus was fragmented by overexpression of the five of the family members.
      Some of the members were found to interact by yeast two-hybrid analysis,
      suggesting the formation of a complex. These results suggest that FinGERs
      function in maintenance of the Golgi structure and/or transport between the ER
      and the Golgi apparatus.

PMID- 14680844
TI  - A mitochondrial DNA variant associated with left ventricular hypertrophy in
      diabetes.
AB  - Diabetes was reported to be associated with a mitochondrial (mt) DNA mutation at
      3243 and variants at 1310, 1438, 3290, 3316, 3394, 12,026, 15,927, and 16,189.
      Among these mtDNA abnormalities, those at 3243, 3316, 15,927, and 16,189 were
      also suggested to cause cardiomyopathies. We investigated the prevalence of such
      mtDNA abnormalities in 68 diabetic patients with LV hypertrophy (LVH), 100
      without LVH, and 100 controls. Among the 9 mtDNA abnormalities, those at 3243,
      3316, and 15,927 tended to be more prevalent in diabetic patients with LVH than
      in those without LVH (1%, 1%, and 4% vs. 0%, 0%, and 0%). Notably, the variant at
      16,189 was more prevalent in diabetic patients with LVH than without LVH (46% vs.
      24%, [Formula: see text] ). The odds ratio for LVH was 3.0 (95% CI, 1.5-6.1) for
      the 16,189 variant. A common mtDNA variant at 16,189 was found to be associated
      with LVH in diabetic patients.

PMID- 14680883
TI  - Assessment of groundwater contamination by nitrate leaching from intensive
      vegetable cultivation using geographical information system.
AB  - This study employed the Geographical Information System (GIS) technology to
      investigate nitrate contamination of groundwater by agrochemical fertilizers in
      the Kakamigahara Heights, Gifu Prefecture, central Japan. Thematic information
      and chemical data of groundwater from the Heights were analyzed in a GIS
      environment to study the extent and variation of nitrate contamination and to
      establish spatial relationships with responsible land use types. The high and
      correlated concentrations of Ca(2+), Mg(2+), SO(4)(2-), and NO(3)(-) reflected
      the polluted nature of the unconfined highly permeable Kakamigahara aquifer.
      Ninety percent of the water samples showed nitrate concentrations above the human
      affected value (3 mg/l NO(3)(-)), while more than 30% have exceeded the maximum
      acceptable level (44 mg/l NO(3)(-)) according to Japan regulations. The spatial
      analyses indicated that groundwater contamination by nitrate is closely
      associated with one specific land use class, the "vegetable fields". The nitrate
      concentration of groundwater under vegetable fields was significantly higher than
      that under urban land or paddy fields. Most of the unacceptable nitrate levels
      were encountered in boreholes assigned to "vegetable fields" but a few were also
      found in boreholes allotted to "urban" class. Therefore, the vegetable fields
      were considered the principal source of nitrate contamination of groundwater in
      the Kakamigahara. However, contamination from urban sources is also possible.

PMID- 14680885
TI  - Phytoaccumulation of heavy metals by aquatic plants.
AB  - Three aquatic plants were examined for their ability to remove heavy metals from
      contaminated water: parrot feather (Myriophylhum aquaticum), creeping primrose
      (Ludwigina palustris), and water mint (Mentha aquatic). The plants were obtained
      from a Solar Aquatic System treating municipal wastewater. All the three plants
      were able to remove Fe, Zn, Cu, and Hg from the contaminated water. The average
      removal efficiency for the three plant species was 99.8%, 76.7%, 41.62%, and
      33.9% of Hg, Fe, Cu, and Zn, respectively. The removal rates of zinc and copper
      were constant (0.48 mg/l/day for Zn and 0.11 mg/l/day for Cu), whereas those of
      iron and mercury were dependent on the concentration of these elements in the
      contaminated water and ranged from 7.00 to 0.41 mg/l/day for Fe and 0.0787 to
      0.0002 mg/l/day for Hg. Parrot feather showed greater tolerance to toxicity
      followed by water mint and creeping primrose. The growth of creeping primrose was
      significantly affected by heavy metal toxicity. The selectivity of heavy metals
      for the three plant species was the same (Hg>Fe>Cu>Zn). The mass balance
      preformed on the system showed that about 60.45-82.61% of the zinc and 38.96
      60.75% of the copper were removed by precipitation as zinc phosphate and copper
      phosphate, respectively.

PMID- 14680884
TI  - Assessment of contamination by heavy metals and petroleum hydrocarbons in
      sediments of Montevideo Harbour (Uruguay).
AB  - As part of the first environmental assessment within Montevideo Harbour, in
      summer and winter of 1998, sediments samples were collected at eight locations to
      determine the spatial distribution of anthropogenic pollutants. Muddy sediments
      with high organic matter content dominate the study area. Heavy metal levels
      indicated that sediments were highly polluted with Zn (overall mean: 312+/-102
      microg g(-1) dry sediment), Pb (85+/-31), Cu (89+/-25), Cr (162+/-62), and Hg
      (0.63+/-0.3) and moderately with Ni (30+/-2) and Ag (1.2+/-0.4). Depending on
      location and season, aliphatic hydrocarbons reached from 21 to 120 microg g(-1),
      while the unresolved complex mixture represented up to 76% of the total aliphatic
      fraction. Total PAH concentrations ranged from 1.56 to 90.44 microg g(-1); except
      at one location, petroleum derivatives were identified as main local source. The
      results pointed out that almost all the harbour area presented some substances
      that can cause adverse biological effects, especially in the inner region where
      all metals are above PEL levels. Principal components analysis confirmed that the
      inner harbour region is most severely affected by the pollutants and it was
      possible to differentiate three regions according to their environmental quality.

PMID- 14680886
TI  - Monitoring environmental pollution in Erzurum by chemical analysis of Scots pine
      (Pinus sylvestris L.) needles.
AB  - Pollution distribution maps of copper (Cu), zinc (Zn) and lead (Pb) for Erzurum
      province were developed on the basis of chemical analysis of Scots pine (Pinus
      sylvestris L.) needles collected from randomly selected sampling points during 2
      years. The maps show deposition zones for the studied elements and could help in
      identification of sources and directions of air pollution dispersion. This study
      indicated that vegetation in Erzurum was greatly endangered by sulphur dioxide
      (SO(2)), whereas Zn does not pose an immediate threat to vegetation in most of
      the country's territory. However, in the city center, main and secondary road
      agglomeration, very high pollution with Pb and Cu could limit growth. Higher
      levels of SO(2) measured in some areas of Erzurum might be harmful for human and
      animal health. Results of this study indicated that Scots pine needles were not
      contaminated by Zn.

PMID- 14680887
TI  - Effect of NOM characteristics on brominated organics formation by ozonation.
AB  - In this study, organic fractions, namely, humic acid, fulvic acid, hydrophobic
      base and neutral, and hydrophilic acid, base, and -neutral, were extracted from
      source water. First, the characteristics of the organic fractions, such as
      carboxylic acidity, phenolic acidity, ultraviolet absorbance, and aromatic
      content, were analyzed. Further, a systematic study was carried out to the by
      products obtained when organic fractions, to which various amounts of bromide had
      been added, were oxidized with ozone. Samples after ozonation were analyzed for
      several brominated organics. The results indicate that the characteristics of the
      aquatic organic matter, including carboxylic/phenolic acidity, aromatic/aliphatic
      content, and ultraviolet absorbance, appear to affect the formation of
      halogenated organics. In general, hydrophobic organics having higher phenolic
      acidity, aromatic content, and ultraviolet absorbance have higher ozone
      consumption and produce higher concentrations of brominated organics than
      hydrophilic organics. It was also found that humic acid demonstrated the highest
      bromoform (CHBr(3)), dibromoacetic acid (DBAA), and 2,4-dibromophenol (2,4-DBP)
      formation, whereas hydrophilic neutral produced less CHBr(3) and 2,4-DBP than the
      rest of the organic fractions but produced the highest amount of dibromoacetone
      (DBAC) and dibromoacetonitrile (DBAN).

PMID- 14680888
TI  - Monitoring of eutrophication and nutrient limitation in the Izmir Bay (Turkey)
      before and after Wastewater Treatment Plant.
AB  - The distribution of inorganic nutrients and phytoplankton chlorophyll-a was
      investigated and N/P ratios were determined in Izmir Bay during 1996-2001. The
      average concentrations showed ranges of 0.01-0.19 and 0.01-10 microM for
      phosphate-phosphorus; 0.11-1.8 and 0.13-27 microM for (nitrate+nitrite)-nitrogen,
      0.30-4.1 and 0.50-39 microM for silicate and 0.02-4.3 and 0.10-26 microg l(-1)
      for chlorophyll-a in the outer and middle-inner bays, respectively. The results
      are compared with the values obtained from the relatively unpolluted waters of
      the Aegean Sea. The N/P ratio is significantly lower than the assimilatory
      optimal (N/P=15:1) in conformity with Redfield's ratio N/P=16:1. Nitrogen is the
      limiting element in the Izmir Bay. Phosphate, which originates from detergents,
      is an important source for eutrophication in the bay, especially in the inner
      bay. In early 2000, a Wastewater Treatment Plant (WTP) began to treat domestic
      and industrial wastes. This plant treats the wastes about 60% capacity between
      2000 and 2001. The sampling periods cover before and after treatment plant.
      Although the capacity of wastewater plant is sufficient for removal of nitrogen
      from the wastes, it is inadequate for removal of phosphate. This is also in
      accordance with the decreasing N/P ratios observed during 2000-2001 (after WTP)
      in the middle-inner bays.

PMID- 14680889
TI  - Probabilistic indicators of atmospheric transport for regional monitoring and
      emergency preparedness systems.
AB  - In this paper, following a methodology developed within the "Arctic Risk" Project
      of the Nordic Arctic Research Programme, several probabilistic indicators to
      evaluate the risk site possible impact on the geographical regions, territories,
      countries, counties, cities, etc., due to atmospheric transport from the risk
      site region were suggested. These indicators-maximum possible impact zone,
      maximum reaching distance, and typical transport time-were constructed by
      applying statistical methods and using a dataset of isentropic trajectories
      originated over the selected nuclear risk site (Ignalina nuclear power plant,
      Lithuania) during 1991-1996. For this site, the areas enclosed by isolines of the
      maximum possible impact zone and maximum reaching distance indicators are equal
      to 42 x 10(4) and 703 x 10(4) km(2), respectively. The maximum possible impact
      zone's boundaries are more extended in the southeast sector from the site and
      include, in particular, Latvia, Lithuania, Belarus, and several western regions
      of Russia. The maximum reaching distance's boundaries are twice more extended in
      the eastern direction from the site (reaching the Caspian Sea) compared with the
      western direction. The typical transport time to reach the southern territories
      of Sweden and Finland, northern regions of Ukraine, and northeast of Poland is 1
      day. During this time, the atmospheric transport could typically occur over the
      Baltic States, Belarus, and western border regions of Russia, and central
      aquatoria of the Baltic Sea. Detailed analysis of temporal patterns for these
      indicators showed importance of the seasonal variability.

PMID- 14680890
TI  - Volumetric assessment of airborne fungi in two sections of a rural indoor dairy
      cattle shed.
AB  - There is increasing concern about the exposure to fungal aerosols in occupational
      environments and associated respiratory allergic diseases and asthma. A large
      number of people work in cattle sheds around the world, pulmonary function
      impairments and higher frequency of respiratory symptoms have been reported in
      dairy farmers; however, it appears that adequate information on the fungal
      aerosols from the cattle sheds are largely lacking. Volumetric assessment of
      airborne culturable and nonculturable fungal spores was performed in two sections
      of a large rural indoor cattle shed of West Bengal, India for 2 consecutive
      years. An Andersen Two Stage Viable Sampler was used for sampling culturable
      fungi and a Burkard Personal Slide Sampler was used to collect the total airborne
      fungal spores including both the culturable and nonculturable types. A total of
      31 spore types and 35 types of viable colony-forming units were recorded. Average
      concentration range of total fungal spores was 233-2985/m(3) and concentration of
      viable colony-forming units ranged between 165 and 2225 CFU/m(3). Burkard Sampler
      showed higher frequencies of Aspergilli/Penicilli, Cladosporium, Alternaria, and
      smut spores. Andersen Sampler showed the prevalence of Aspergillus niger,
      Aspergillus flavus and Cladosporium cladosporioides colonies. Some recorded fungi
      were earlier reported as allergenic, toxic, and pathogenic for occupational
      workers as well as cattle population. Higher concentration levels of airborne
      total and culturable fungal spores were recorded during the months of November
      through February (winter) and June through September (late summer and rainy
      season).

PMID- 14680891
TI  - The composting potential of different organic solid wastes: experience from the
      island of Crete.
AB  - For the past 20 years, the National Foundation for Agricultural Research in Crete
      and the School of Agricultural Technology of the Technological and Educational
      Institute of Crete have been involved in a number of research and development
      activities, related to the production and evaluation of compost derived from a
      variety of local solid, mainly agricultural organic wastes. Materials such as
      olive press cake, olive tree leaves (OTL) and branches, vine branches (VB),
      pressed grape skins (PGS), pig manure (PM), sewage sludge and the organic
      fraction of municipal solid waste (OFMSW) have been evaluated for their behaviour
      during composting, their compatibility in mixtures and the quality of the end
      product. The quality evaluation included both a detailed physiochemical (pH,
      electrical conductivity (EC), nutrients concentration, heavy metal concentration,
      etc.) and biological analyses (pathogenic microorganisms). It also included an
      agronomic evaluation, in which composts were used either as a soil amendment or
      as a component for substrates in open air or covered (greenhouse) cultivation
      mainly of local vegetables (tomatoes, cucumbers, etc.). All materials were
      composted successfully, especially when mixed. The end products contained large
      amounts of organic matter, usually combined with an increased EC value. Pressed
      grape skins should be considered as the ideal raw material, producing a high
      quality compost, with the lowest EC value (1.57 mS cm(-1)) and the largest
      organic matter concentration (84.50%), compared to all other materials. When any
      of the produced compost was used in a ratio of 30% by volume (v/v), it increased
      plant growth, whereas in larger volumes, it presented phytotoxic behaviour,
      inhibiting both root and shoot development.

PMID- 14680892
TI  - Natural gamma radiation map (MARNA) and indoor radon levels in Spain.
AB  - During the last decade, the Department of Applied and Medical Physics has been
      involved in the development of a radiation protection programme. In the framework
      of this programme, measurements of indoor radon, principally, have been carried
      out nationwide. Geometric mean radon concentrations of 45 Bq m(-3) in the whole
      country and 130 Bq m(-3) in the high natural radiation area have been estimated.
      On the other hand, the so-called MARNA Project is developed into the framework of
      an agreement subscribed between the Spanish Nuclear Safety Council (CSN) and the
      National Uranium (ENUSA), the first phase of which has been the elaboration of
      the Natural Gamma Radiation Map of Spain on the scale of 1:1,000,000 using
      radiometric data generated in the 30 years of the lifetime of the ancient
      National Uranium Exploration and Investigation Plan mainly through airborne,
      carborne, and by foot surveys, within the MARNA Project itself. The lowest
      averaged dose rate from external gamma radiation (19.3 nGyh(-1)) was found in
      carbonate bedrock and the highest (87.7 nGyh(-1)) was found in granite and clay
      bedrock. This paper summarizes the main results obtained from the measurements
      performed in both projects, with special interest in those concerning the
      correlation between the data reported in order to conclude about the potential
      benefit of the MARNA maps in the definition of affected areas in the country.

PMID- 14680893
TI  - Toxicities and tolerances of Cd, Cu, Pb and Zn in a primary producer (Isochrysis
      galbana) and in a primary consumer (Perna viridis).
AB  - Studies on toxicities and tolerances of cadmium (Cd), copper (Cu), lead (Pb) and
      zinc (Zn) in the brown alga Isochrysis galbana and in the green-lipped mussel
      Perna viridis were conducted by short-term bioassays using endpoints growth
      production and mortality, respectively. The 5-day EC(50) and 24-h LC(50) of these
      heavy metals were determined in the brown alga and mussel, respectively. The
      EC(50) values calculated for the alga were 0.74 mg/l for Cd, 0.91 mg/l for Cu,
      1.40 mg/l for Pb and 0.60 mg/l for Zn. The LC(50) values for the mussels were
      1.53 mg/l for Cd, 0.25 mg/l for Cu, 4.12 mg/l for Pb and 3.20 mg/l for Zn. These
      LC(50) values were within the concentration ranges as reported by other authors
      who used P. viridis as the test organism. Based on these EC(50) and LC(50)
      values, the alga was most sensitive to Zn, followed by Cd, Cu and Pb while the
      mussel was most sensitive to Cu, followed by Cd, Zn and Pb. Differences in the
      trophic levels, metal handling strategies, biology and ecology of the primary
      producer (brown alga) and the primary consumer (mussel) are believed to be the
      plausible causes for the different toxicities and tolerances of the metals
      studied.

PMID- 14680894
TI  - The setting of standards for agricultural nitrogen emissions: a case study of the
      Delphi technique.
AB  - The Delphi technique is a means of aggregating the judgement of a panel of
      experts in order to improve the quality of decision-making. This paper provides a
      case study of the technique by undertaking a three-round Delphi study to
      determine a package of best available techniques to reduce nitrogen emissions
      from a poultry unit under the Integrated Pollution Prevention and Control
      Directive (IPPC). Forms of nitrogen addressed included ammonia (NH3), nitrous
      oxide (N2O) nitrogen oxides (NOx), dusts and nitrate (NO3-), with the study
      providing a means to prioritise the pollution concerns on different spatial
      scales. The priority pollutant issues were the contribution of NH3 to
      eutrophication, the global cooling effect of NH4+ aerosol, the role of NH4+ as a
      vector for atmospheric transport of NOx and SO2, the contribution of N2O to
      global warming, and NO3- leaching. Reduced nitrogen (NHx) was rated as a priority
      on all scales, while N2O and NO3- were rated as priorities only on global and
      local scales, respectively. The study indicated the need for abatement techniques
      at each stage of poultry rearing and waste management, with particular attention
      to reduce NH3 emissions, reflecting the priority pollutant concerns. Measures
      identified by the panel include maintenance of dry litter, low emission removal
      of litter from housing and storage of litter under cover. Once the litter has
      left the farm, this should either be used as a biofuel for electricity generation
      or rapidly incorporated into agricultural soils. The amounts and timing of manure
      application should be tuned to crop needs. Uncertainties in the Delphi technique
      limit its suitability as a stand-alone decision making tool. However, the Delphi
      technique proved useful in identifying priority pollutant issues, areas of
      agreement, disagreement and where information is lacking. This demonstrates its
      use when dealing with the complex issues of prioritising pollution issues and
      abatement approaches.

PMID- 14680895
TI  - Local people's attitudes towards conservation and wildlife tourism around Sariska
      Tiger Reserve, India.
AB  - Conservationists in the recent years view local peoples' support for protected
      areas management as an important element of biodiversity conservation. This is
      often linked to the direct benefits, which local communities get from the
      protected areas. These benefits could be in the form of biomass resources, park
      funds diverted to local villages by state agencies and revenue from wildlife
      tourism. There are a very few studies which have attempted to study the direct
      relationship between benefits from wildlife tourism and local support for
      conservation. In India, wildlife tourism is restricted, and mostly controlled by
      state and private agencies. Wildlife conservation policy does not view tourism in
      protected areas as a source of revenue for the local communities. The present
      study examines the local people's attitudes towards wildlife tourism and the
      impact of benefits from tourism on the local support for Sariska Tiger Reserve
      (STR), India. STR is a flagship for tourism where protected areas are
      increasingly being visited and where local support for wildlife tourism has not
      been studied adequately. Results indicate that two-thirds of the respondents were
      positive towards tourism and support for conservation. The respondents were aware
      that more tourism benefits are possible from a well-conserved protected area.
      There appears to be correlation between benefits obtained by local people from
      wildlife tourism and other sources, and support for protected area existence,
      suggesting that benefits impact people's attitudes towards conservation. Some of
      the main problems are the unequal distribution of tourism benefits, lack of
      locals' involvement in tourism and development. There is a need to clearly
      address these issues, so that protected areas may get the support of local
      people, which may lead to sustainable development.

PMID- 14680896
TI  - Evaluating the management strategies of a forestland estate--the S-O-S approach.
AB  - Connecting Multiple Criteria Decision Support (MCDS) methods with SWOT
      (Strengths, Weaknesses, Opportunities, and Threats) analysis yields analytical
      priorities for the factors included in SWOT analysis and makes them
      commensurable. In addition, decision alternatives can be evaluated with respect
      to each SWOT factor. In this way, SWOT analysis provides the basic frame within
      which to perform analyses of decision situations. MCDS methods, in turn, assist
      in carrying out SWOT more analytically and in elaborating the results of the
      analyses so that alternative strategic decisions can be prioritized also with
      respect to the entire SWOT. The A'WOT analysis is an example of such hybrid
      methods. It makes combined use of the Analytic Hierarchy Process (AHP) and SWOT.
      In this study, a hybrid method of the Stochastic Multicriteria Acceptability
      Analysis with Ordinal criteria (SMAA-O) and SWOT is developed as an elaboration
      of the basic ideas of A'WOT. The method is called S-O-S (SMAA-O in SWOT). SMAA-O
      enables the handling of ordinal preference information as well as mixed data
      consisting of both ordinal and cardinal information. Using SMAA-O is enough to
      just rank decision elements instead of giving them cardinal preference or
      priority ratios as required by the most commonly used MCDS methods. Using SMAA-O,
      in addition to analyzing what the recommended action is under certain priorities
      of the criteria, enables one to analyze what kind of preferences would support
      each action. The S-O-S approach is illustrated by a case study, where the
      shareholders of a forest holding owned by a private partnership prepared the SWOT
      analysis. Six alternative strategies for the management of their forest holding
      and of old cottage located on the holding were formed. After S-O-S analyses were
      carried out, one alternative was found to be the most recommendable. However,
      different importance orders of the SWOT groups would lead to different
      recommendations, since three of the six alternatives were efficient according to
      S-O-S analyses.

PMID- 14680897
TI  - Wildfire effects on hiking and biking demand in New Mexico: a travel cost study.
AB  - We use a travel cost model to test the effects of wild and prescribed fire on
      visitation by hikers and mountain bikers in New Mexico. Our results indicate that
      net benefits for mountain bikers is $150 per trip and that they take an average
      of 6.2 trips per year. Hikers take 2.8 trips per year with individual net
      benefits per trip of $130. Both hikers' and mountain bikers' demand functions
      react adversely to prescribed burning. Net benefits for both groups fall as areas
      recover from prescribed burns. Because both visitation and annual recreation
      benefits decrease to these two types of visitors, this gives rise to multiple use
      costs associated with prescribed burning. With respect to wildfire, hikers and
      mountain bikers both exhibit decreased visitation as areas recover from
      wildfires, however, only hikers indicate an increase in per trip net benefits.
      Bikers' demand effectively drops to zero. These results differ from previous
      findings in the literature and have implications for efficient implementation of
      the National Fire Plan and whether prescribed burning is a cost effective tool
      for multiple use management of National Forests. Specifically, that fire and
      recreation managers cannot expect recreation users to react similarly to fire
      across recreation activities, or different geographic regions. What is cost
      effective in one region may not be so in another.

PMID- 14680898
TI  - Agricultural drainage and wetland management in Ontario.
AB  - Land drainage is recognized as an integral part of agricultural activity
      throughout the world. However, the increase in agricultural production has
      resulted in the loss of wetland functions and values. Therefore, wetland
      management and agricultural drainage illustrate the conflict between economic
      development and natural values. This research assesses the approval process for
      agricultural land drainage in Ontario, Canada, to determine how the benefits of
      increased agricultural production are balanced against the loss of wetland
      values. A permit review of drainage applications was conducted from 1978 to 1997
      in Zorra Township, Ontario, Canada. Data collection also included the document
      reviews, interviews with government agencies and wetland evaluation files. The
      selected criteria include efficiency, equity, consistency and adequacy. The
      results indicate that while the process is efficient, fundamental problems remain
      with the bargaining process.

PMID- 14680899
TI  - EMMC process for combined removal of organics, nitrogen and an odor producing
      substance.
AB  - In order to improve the process performance regarding the removal of organics,
      nitrogen, and an odor-causing compound (sulfide) contained in domestic
      wastewater, an entrapped-mixed-microbial cell (EMMC) with and without humic
      substances for both fixed and moving carrier reactors and conventional suspended
      growth culture (i.e. conventional activated sludge process) were investigated
      simultaneously. Both synthetic (simulated to the organics concentration of
      general domestic sewage) and actual domestic wastewater were investigated under
      operational conditions of 12 h of hydraulic retention time (HRT) with 1 h of
      aeration and 1 h of non-aeration, and 6 h of HRT with continuous aeration, at a
      room temperature of 25 +/- 2 degrees C. It was found that entrapping humic
      substances in the EMMC carriers had no impact on the removal of organics,
      nitrogen, and the odor-producing compound. Additionally, the performance of the
      EMMC moving carrier system for the removal of these pollutants is similar to that
      of the EMMC fixed carrier system. In general, the EMMC associated systems which
      provide high solids retention time achieve a better removal of chemical oxygen
      demand (COD), nitrogen, and the odor-producing substance than the suspended
      growth system for both HRTs of 6 h (continuous aeration) and 12 h (1 h of
      aeration and 1 h of non-aeration). Both the fixed and moving carrier EMMC
      processes, therefore, have the potential for improvement or replacement of the
      existing conventional activated sludge process with regard to improving the
      effluent qualities (such as COD, nitrogen and odor-producing compound) for
      reuse/disposal.

PMID- 14680900
TI  - A framework for profiling a lake's riparian area development potential.
AB  - Some of the greatest challenges for managing residential development occur at the
      interface between the terrestrial and aquatic ecosystems--in a lake's riparian
      area. Land use planners need a framework they can use to identify development
      hotspots, areas were the next push for development will most likely occur. Lake
      riparian development profiles provide a framework for linking ecological and
      social factors important to development. In a test of this framework in northern
      Minnesota, researchers identified seven constructs influencing riparian area
      development: current general development, current housing development, and
      availability, accessibility, suitability, aesthetics, and proximity to services.
      Profiles display a lake's value for each construct relative to the range of
      values for all lakes in the county. Maps, developed using indicators for several
      constructs, allow us to identify how the factors interact and are dispersed
      across the landscape. These profiles help policy makers, planners, and managers
      identify lakes that are potential development hotspots so they can take timely
      steps to manage development or control the impacts of development.

PMID- 14680901
TI  - Developing sustainable water management scenarios by using thorough hydrologic
      analysis and environmental criteria.
AB  - Wetlands constitute a significant source of life since they incorporate unique
      habitats with endemic and migrant species. They also contribute to the
      preservation of high global biodiversity and they are under protection according
      to EU legislation. Nevertheless, during the last century, significant degradation
      has been observed in wetlands, mainly due to intensification of agriculture and
      poor water management practices. Calcareous fens habitat with the endangered
      species Cladium mariscus and Carex spp. is an ecologically significant wetland
      that undergoes great ecological stresses globally, due to the irrational use of
      water resources. In Trichonis lake, Western Greece, this habitat has been under
      deterioration during the last 50 years due to the lack of a sustainable water
      management plan that has caused destabilization of the hydrologic balance and
      high water level fluctuations. This human induced hydrologic regime has led to
      seasonal shifting between drought and flooding which constitute unfavorable
      conditions for this fen habitat and as a result significant elimination of this
      ecosystem extent has occurred. This study has adopted technologically advanced
      scientific methods such as GIS applications and remote sensing techniques to
      quantify the existing water resources and formulate a sustainable management
      scheme by considering both anthropogenic water uses and environmental protection.

PMID- 14680903
TI  - High field MRI.

PMID- 14680904
TI  - High field functional MRI.
AB  - Functional magnetic resonance imaging (fMRI) has become the most widely used
      approach for studying brain functions in humans. The rapid and widespread
      diffusion of fMRI has been favoured by the properties this technique presents,
      and particularly by its sensitivity in analysing brain functional phenomena and
      by the lack of biological invasiveness, resulting in an unprecedented and
      unparalleled flexibility of use. These properties of fMRI brought the functional
      examination of the brain within the reach of the whole neuroscience community and
      have appreciably stimulated the research on the functional processes of the
      living brain. Among the main features of fMRI, its spatial and temporal
      resolution represents clear advantages compared with the other methods of
      functional neuroimaging. In fact, the high spatial resolution of fMRI permits to
      produce more precise and better localised information, and its temporal
      resolution provides the potential of a better understanding of neural dynamics at
      the level of single functional areas and of the neural constituents of functional
      patterns. A fundamental possibility of improving spatial and temporal resolution
      without excessively degrading signal-to-noise ratio consists in the use of high
      magnetic field intensity fMRI units. Besides, high field units make the use of
      more demanding fMRI paradigms, like single trial event related studies, much more
      compatible with the need of a solid statistical evaluation. This has notably
      promoted the diffusion of high field MRI units for human studies throughout the
      world, with very high field MRI units, up to 8 T, working in a few research
      centres, and a larger number of MRI units with field intensity ranging between 3
      and 5 T.

PMID- 14680905
TI  - High-field proton MRS of human brain.
AB  - Proton magnetic resonance spectroscopy (1H-MRS) of the brain reveals specific
      biochemical information about cerebral metabolites, which may support clinical
      diagnoses and enhance the understanding of neurological disorders. The advantages
      of performing 1H-MRS at higher field strengths include better signal to noise
      ratio (SNR) and increased spectral, spatial and temporal resolution, allowing the
      acquisition of high quality, easily quantifiable spectra in acceptable imaging
      times. In addition to improved measurement precision of N-acetylaspartate,
      choline, creatine and myo-inositol, high-field systems allow the high-resolution
      measurement of other metabolites, such as glutamate, glutamine, gamma
      aminobutyric acid, scyllo-inositol, aspartate, taurine, N
      acetylaspartylglutamate, glucose and branched amino acids, thus extending the
      range of metabolic information. However, these advantages may be hampered by
      intrinsic field-dependent technical difficulties, such as decreased T2 signal,
      chemical shift dispersion errors, J-modulation anomalies, increased magnetic
      susceptibility, eddy current artifacts, limitations in the design of homogeneous
      and sensitive radiofrequency (RF) coils, magnetic field instability and safety
      issues. Several studies demonstrated that these limitations could be overcome,
      suggesting that the appropriate optimization of high-field 1H-MRS would expand
      the application in the fields of clinical research and diagnostic routine.

PMID- 14680906
TI  - 3.0 T magnetic resonance in neuroradiology.
AB  - Ever since the introduction of magnetic resonance (MR), imaging with 1.5 T has
      been considered the gold standard for the study of all body areas. Until not long
      ago, higher-field MR equipment was exclusively employed for research, not for
      clinical use. More recently, the introduction of 3.0 T MR machines for new and
      more sophisticated clinical applications has yielded in important benefits,
      especially in neuroradiology. Indeed, their high gradient power and field
      intensity allow adjunctive and more advanced diagnostic methodologies to be
      applied with excellent resolution in a fraction of the time of acquisition
      compared with earlier machines. The numerous advantages of these machines in
      terms of higher signal, increased spatial resolution and greater sensitivity, and
      their few limitations, which can be overcome and anyway do not adversely affect
      diagnostic efficacy, will make 3.0 T MR systems the gold standard for
      morphological and functional studies of the brain.

PMID- 14680907
TI  - High field MRI in preclinical research.
AB  - High fields magnetic resonance imaging (MRI) experiments on humans have been
      historically limited by the so called "penetration effect" of B1 and by the power
      deposition in living tissues. The first effect refers to the non-homogeneous
      value of B1 field inside the sample (important when the wavelength of the r.f.
      field approaches the dimension of the sample i.e. when the Larmor frequency
      increase above 10-20 MHz) and the second refers to the increase in the power
      deposition in tissues when the Larmor frequency increases. Both phenomena are
      less important in animals, because of the smaller dimensions of animal bodies and
      the less stringent safety requirements. As a result, animal instruments were
      developed at high fields earlier compared with human ones. Today the great
      majority of imagers designed for animal studies operate at fields of 4.7 T or
      higher. The main advantages in high fields stand in higher signal to noise ratio
      (and consequent increase in space resolution or decrease in acquisition time) and
      higher frequency separation between metabolite peaks in in vivo spectroscopy.
      Disadvantages are in the higher cost of magnets and electronics, in shortening of
      T2 relaxation time, paralleled by a lengthening in T1 relaxation time, and in
      greater importance of susceptibility and chemical shift artefacts. Recent
      developments in applications of MRI (and magnetic resonance spectroscopy, MRS) in
      preclinical studies, as for example functional magnetic resonance imaging (fMRI),
      microscopy, diffusion-weighted (DW) spectroscopy and molecular imaging, pose
      increasing requirements to technical aspects of MRI instruments (increased signal
      to-noise ratio (SNR), space resolution and chemical shift) and consequently push
      toward higher magnetic fields. In this paper the above mentioned developments are
      reviewed and discussed.

PMID- 14680908
TI  - Transverse sinus air after cranial trauma.
AB  - Air in vascular compartments has been rarely reported. We report a case in whom
      air within transverse sinus and sinus confluence through ruptured superior
      sagittal sinus (SSS) due to fractures of parietal and frontal bones was disclosed
      by computed tomography (CT). Although air in transverse sinus has been reported
      rarely this could be the first case with air in transverse sinus through the SSS
      after cranial trauma.

PMID- 14680909
TI  - Marchiafava-Bignami disease: magnetic resonance imaging findings in corpus
      callosum and subcortical white matter.
AB  - A case of Marchiafava-Bignami disease (MBD) is presented using magnetic resonance
      imaging (MRI). A patient with a long history of alcoholism developed a gait
      disturbance with involuntary movements at the lower extremities. MRI scans taken
      at the onset showed no particular abnormalities. He progressed to a coma 10 days
      later. MRI scans taken 20 days after the onset showed a focal lesion at the genu
      of the corpus callosum and he was diagnosed as having MBD. In addition, multiple
      lesions were observed in bilateral frontoparietal subcortical white matter. These
      lesions demonstrated similar intense MRI signals as the corpus callosum.

PMID- 14680910
TI  - MR imaging of epithelial cysts of the oral and maxillofacial region.
AB  - The aim of the present study was to review the magnetic resonance (MR) appearance
      of primary epithelial cysts in order to distinguish the cysts from other possible
      lesions. MR images were obtained in 27 cases of epithelial cysts, including 7
      odontogenic keratocysts, 3 dentigerous cysts, 1 glandular odontogenic cyst, 10
      radicular cysts, 4 nasopalatine duct cysts, and 2 nasolabial cysts. In addition,
      contrast enhanced MR imagings were performed in 12 cases, including 3 odontogenic
      keratocysts, 1 dentigerous cyst, 1 glandular odontogenic cyst, and 7 radicular
      cysts. We obtained the following results on the basis of the above MR and
      contrast enhanced MR findings. (a) Odontogenic keratocysts had a predilection for
      intermediate-high signal intensity (SI) on T1-weighted images (WI) and
      heterogeneous low-high SI on T2WI. (b) Dentigerous cysts, glandular odontogenic
      cyst, radicular cysts and nasolabial cysts showed the same predilection with the
      SI, which were homogeneous intermediate SI on T1WI and homogeneous high SI on
      T2WI. (c) The MR images of the nasopalatine duct cysts, which showed homogeneous
      high SI on T1WI, were specific. (d) The Gd-T1WI would be useful in decisively
      differentiating odontogenic cysts, which showed rim-enhancement, from tumors
      consisting of solid components. In conclusion, we were able to obtain more
      information from the MR and contrast enhanced MR images than from conventional
      radiograph findings.

PMID- 14680911
TI  - The value of dynamic contrast-enhanced MRI in diagnosis of malignant lymphoma of
      the head and neck.
AB  - In this study, we attempted to diagnose malignant lymphoma on the basis of
      magnetic resonance imagings (MRIs) and dynamic contrast-enhanced MRI (DCE-MRI).
      Eighteen lesions (in eight patients), all of which had been proven
      histopathologically, were detected on MRI. The eight patients included five
      patients with diffuse large B-cell lymphoma, one with B-cell low-grade MALT
      lymphoma, one with follicular lymphoma, and one with Hodgkin's lymphoma. Nine
      lesions were located in the submandibular region, three in the buccal region, two
      in the orbit region, two in the submental region, and one each in the palatal and
      tonsil regions. The diameter of the lesions ranged between 9 and 42.2 mm
      (average: 22.4 mm). The signal intensities (SIs) of the 18 lesions were examined
      on T1-weighted (T1WI), T2WI, and gadopentetate (Gd)-T1WI. One lesion in case 8
      was excluded from DCE-MRI findings, i.e., the regions of interest could not be
      adequately set on DCE-MRIs. The contrast index (CI) curves of the remaining 17
      lesions were prepared. All 18 lesions showed almost the same images on T1WI,
      T2WI, and Gd-T1WI, although they represented four types of lymphoma. The images
      showed homogeneous SI that was intermediate to slightly high SI on T1WI, slightly
      high SI on T2WI, and moderately enhanced on Gd-T1WI. Thus, the cases of malignant
      lymphoma in this study showed relatively characteristic features based on MRI;
      however, these features might be non-specific. The CI curves in this study showed
      a relatively rapid increase, reaching a maximum CI at 45-120 s, and a relatively
      rapid decrease in most lesions (14/17; 82.4%); on the other hand, the curves of 3
      of the 15 lesions (17.6%) showed relatively rapid increase, sustenance of a
      plateau, and a gradual decrease thereafter. These patterns of CI curves may
      indicate characteristic features useful for distinguishing malignant lymphomas
      from other lesions.

PMID- 14680912
TI  - CT virtual bronchoscopy in the evaluation of children with suspected foreign body
      aspiration.
AB  - OBJECTIVE: Computed tomography (CT) virtual bronchoscopy is a noninvasive
      technique that provides an internal view of trachea and major bronchi by three
      dimensional reconstruction. The aim of this study was to investigate the
      usefulness of virtual bronchoscopy in the evaluation of suspected foreign body
      aspiration in children. MATERIALS AND METHODS: Twenty-three children (12 girls,
      11 boys) with a mean age of 2.4 years (8 months-14 years) who were admitted to
      emergency room with a suspicion of foreign body aspiration were included in this
      study. Chest radiograms, spiral computed tomography scans and virtual
      bronchoscopy images were obtained. Then, rigid bronchoscopy was performed within
      24 h. RESULTS: CT virtual bronchoscopy and conventional bronchoscopy revealed the
      location of the foreign body in seven patients. It was in the right main bronchus
      in four patients, in the right lower lobe bronchus in one patient, and in the
      left main bronchus in two patients. There was no discordance between two
      modalities. CT examination revealed hyperaeration of the ipsilateral lung in four
      patients, hyperaeration of the ipsilateral lung and mediastinal shift in one
      patient and bronchiectatic changes in one patient. CT detected no additional
      finding in one patient with a foreign body in the right main bronchus. In 10 of
      16 patients without foreign body, CT examination demonstrated atelectasis,
      infiltration, peribronchial thickening, and paratracheal lymphadenpoathy.
      CONCLUSION: Helical CT scanning with virtual bronchoscopy should be performed in
      only selected cases with suspected foreign body aspiration. When the chest
      radiograph is normal and the clinical diagnosis suggests aspirated foreign body,
      helical CT and virtual bronchoscopy can be considered in order to avoid needless
      rigid bronchoscopy.

PMID- 14680913
TI  - CT fluoroscopy-guided percutaneous needle biopsies in thoracic mass lesions.
AB  - OBJECTIVE: We aimed to evaluate the usefulness of computed tomographic (CT)
      fluoroscopy guidance for transthoracic needle biopsies. METHODS AND MATERIAL: CT
      fluoroscopy-guided biopsies were performed in 81 patients with thoracic mass
      lesions. Interrupted CT fluoroscopy technique was used with 50-130 mA at 120 kV
      exposure parameters and slice thickness of 10 mm. We used aspirating needle in 41
      patients, cutting needle in 28 patients, and both in 12 patients. We obtained
      adequate biopsy material in 69 patients at first attempt. Mean fluoroscopy time
      was 15.17 s and maximum procedure time was 18 min. RESULTS: Adequate samples for
      pathological diagnosis were obtained in all lesions. Pathological diagnoses were
      malignant in 41 patients, benign in 27 patients, and suspiciously malignant in 13
      patients. There was no significant difference between diagnostic accuracy of the
      needles in malignant and benign lesions. Complications were observed in 11
      patients (13.5%). DISCUSSION AND CONCLUSION: CT fluoroscopy-guided technique
      provides effective real-time needle biopsy in patients with small tumor size and
      with tumor located near blood vessels, and in non-compliant patients for
      diagnosing thoracic lesions.

PMID- 14680914
TI  - Adrenal adenomas: relationship between histologic lipid-rich cells and CT
      attenuation number.
AB  - OBJECTIVE: To evaluate the relationship between lipid-rich cells of the adrenal
      adenoma and precontrast computed tomographic (CT) attenuation numbers in three
      clinical groups. MATERIALS AND METHODS: Thirty-five surgically resected adrenal
      adenomas were used. The clinical diagnoses of the patients included 13 cases of
      primary aldosteronism, 15 cases of Cushing's syndrome, and 7 non-functioning
      tumors. The number of lipid-rich clear cells was counted using a microscopic
      eyepiece grid that contained 100 squares. The results were expressed as the
      percentages of lipid-rich areas. RESULTS: There was a strong inverse linear
      relationship between the percentage of lipid-rich cells and the precontrast CT
      attenuation number (R(2)=0.724, P<0.0001). There were significantly more lipid
      rich cells in the primary aldosteronism and non-functioning tumor cases compared
      to cases of Cushing's syndrome (P=0.007 and 0.015, respectively). The CT
      attenuation numbers of the primary aldosteronism cases were significantly lower
      than those of Cushing's syndrome (P=0.0052). Furthermore, the CT attenuation
      numbers of the non-functioning tumor cases were lower than those of Cushing's
      syndrome cases. CONCLUSION: We showed that adrenal adenomas in primary
      aldosteronism and non-functioning tumors contain significantly more lipid-rich
      cells than those in Cushing's syndrome. They also showed significantly lower
      attenuation than that in Cushing's syndrome on CT scans. Our results suggest that
      precontrast CT attenuation numbers may be helpful in the differentiation of
      adenomas from non-adenomatous lesions, which include malignancies.

PMID- 14680915
TI  - Hepatic outflow obstruction: enhancement patterns of the liver on MR angiography.
AB  - Our purpose was to present the enhancement patterns of the liver on MR
      angiography in patients with hepatic outflow obstruction. Twenty-three patients
      with Budd-Chiari syndrome (4 in acute stage and 19 in chronic stage of the
      disease) were examined with 3D contrast-enhanced MR angiography. During early and
      late portal venous phase of MR angiography the pattern of parenchymal enhancement
      was assessed on source images. The enhancement patterns were evaluated under 4
      groups as following: (a) central (b) peripheral (c) patchy and (d) homogeneous
      enhancement. The morphologic changes in the liver (lobar hypertrophy or atrophy,
      hepatic surface irregularities) were also recorded. In the acute stage global
      liver enlargement (75%) with caudate hypertrophy (100%) and central enhancement
      of the liver (75%) were suggestive findings of the hepatic outflow obstruction.
      The left lobe hypertrophy (53%) associated with the caudate lobe hypertrophy
      (72%) and irregular surface (26%) were predominant in the chronic stage of the
      disease. The enhancement patterns seen in chronic disease were variable and
      reflected the persistent stasis of the portal blood flow (patchy enhancement in
      32% of the patients) or the altered hemodynamics of the liver due to the
      development of subcapsular collaterals (peripheral enhancement in 21% of the
      patients). Homogeneous enhancement of the liver in Budd-Chiari syndrome may
      indicate the chronicity of the outflow obstruction (37%) and shows a more stable
      hepatic perfusion that occurs after the formation of intra and extrahepatic
      collateral veins. The morphological and perfusional features on multiphase
      contrast-enhanced MR angiography are valuable in understanding the effects of the
      hepatic outflow obstruction on the liver parenchyma.

PMID- 14680916
TI  - Fibrosing mediastinitis and thrombosis of superior vena cava associated with
      Behcet's disease.
AB  - We present CT, MRI and venography findings in 13-year boy with mediastinal
      fibrosis and superior vena cava (SVC) thrombosis associated with Behcet's
      disease. Fibrosing mediastinitis is an excessive fibrotic reaction that occurs in
      the mediastinum and may lead to compression of mediastinal structures (especially
      vascular). This condition is usually idiopathic, though many (and perhaps most)
      cases in the USA are thought to be caused by an abnormal immunologic response to
      Histoplasma capsulatum infection. SVC syndrome secondary to extrinsic compression
      by mediastinal fibrosis combined with Behcet's disease has rarely been described.
      Radiological investigations of this syndrome are necessary to avoid a useless
      anticoagulant therapy.

PMID- 14680917
TI  - Clinical utility of sequential imaging of hepatocellular carcinoma by contrast
      enhanced power Doppler ultrasonograpy.
AB  - The aim of this study was to investigate the clinical utility of sequential
      imaging of hepatocellular carcinoma (HCC) by contrast-enhanced power Doppler
      ultrasonograpy (CE-PDUS) to differentiate hepatocellular carcinoma from
      adenomatous hyperplasia (AH) and regenerated nodule (RN) and to predict the
      degree of differentiation of HCC. Fifty-one patients with 62 hepatic lesions
      including 33 moderately and poorly differentiated HCCs, 19 well-differentiated
      HCCs, seven AHs and three large RNs were examined by CE-PDUS. The imaging
      patterns during early arterial phase (tumor vessel image), late vascular phase
      (tumor perfusion image) and post-vascular phase (liver perfusion image) were
      classified as diffuse, basket, peripheral, central and no enhancement; as whole
      tumor, partial tumor and no enhancement; as whole tumor, partial tumor and no
      defect, respectively. The diffuse pattern in the tumor vessel image, the whole
      enhancement pattern in the tumor perfusion image and the whole defect pattern in
      the liver perfusion image were observed in moderately and poorly differentiated
      HCCs only. The basket pattern in the tumor vessel image and the partial defect
      pattern in the tumor perfusion image were observed in HCCs only. All AH/RNs
      showed no defect pattern in the liver perfusion image. The sequential imaging of
      HCC during early arterial, late vascular and post-vascular phases by CE-PDUS is
      clinically useful to differentiate HCC from AH/RN and to predict the degree of
      differentiation of HCC.

PMID- 14680918
TI  - Quiz case. Trichinosis associated muscular calcifications.

PMID- 14680919
TI  - Mouthparts of Megaselia scalaris (Loew) (Diptera: Phoridae).
AB  - Mouthparts of adult Megaselia scalaris (Loew), a fly species of medical
      importance, were examined using scanning electron microscopy. Sexual dimorphism
      of the labellum was observed in the mouthpart structures of this species. The
      labella of males were clothed with a dense covering of microtrichia, but these
      were found to be entirely absent from the labella of females. Aside from this
      difference, trichoid and conical sensilla that are most likely used as taste or
      contact chemoreceptors appear on the labellum and labrum of both sexes. In
      addition, five pairs of sharply pointed teeth at the ventral surface of the
      labellum is another feature that is shared by the two sexes. A plausible feeding
      mechanism for this fly is also advanced.

PMID- 14680920
TI  - Whole-mount sections displaying microvascular and glandular structures in human
      uterus using multiphoton excitation microscopy.
AB  - There has been considerable interest over many years in the precise structural
      relationships between microvessels and secretory glands in human endometrium.
      However, microcirculatory networks have rarely been studied in three-dimensions
      (3D) using modern computerised technologies, this has been partly due to the late
      arrival of suitable endothelial cell markers. This study was designed to develop
      a technique to visualize and to reveal the relationships between microvessels,
      their glandular environment and epithelial boundaries in 3D, using endometrium
      from human hysterectomy biopsies. Specimens were carefully selected from women
      with conditions unlikely to affect the microvascular networks. Monoclonal
      antibodies (mouse anti-human CD 34 and goat anti-mouse fluorescein (FITC)) were
      used to visualize the microvessels, and polyclonal antibodies (rabbit anti-human
      keratin and goat anti-rabbit tetramethylrhodamine (TRITC)) were used to visualize
      the glandular structures. The samples were studied with a Leica multiphoton
      system using a titanium-sapphire laser (excitation 800 nm with pulses in the 200
      fs range) to obtain a stack of two-dimensional (2D) images to a minimal focus
      depth of 120 microm. The initial data sets acquired were volume rendered using
      the integrated software of the Leica system to produce 3D images. This software
      allowed for the acquisition of data sets from the microscope and for an
      observational morphological assessment to be made, but was limited in preparing
      the data for any quantitative analysis. The additional use of ImarisBasic 3.1
      visualization software allowed for an observational morphological assessment but
      also included numerous tools for data manipulation.

PMID- 14680921
TI  - Larval ultrastructure of Parasarcophaga dux (Thomson) (Diptera: Sarcophagidae).
AB  - Ultrastructure of all larval instars of Parasarcophaga dux (Thomson), a common
      flesh fly species in Thailand, is presented using scanning electron microscopy.
      Special attention is given to the structure of anterior and posterior spiracles
      since these are important features used to differentiate between other
      sarcophagids. Each anterior spiracle in second and third instars has a single row
      of papillae varying in number from 14 to 17. The posterior spiracular discs have
      incomplete peritremes, with a prominent inner arc. Three long, narrow spiracular
      slits are oriented more or less vertically in each spiracular disc of third
      instar. Posterior spiracular hairs lack extensive branching and emanate
      approximately midway down the length of each slit. Microscopic morphology of the
      mouthhooks markedly differs between the first and second instars. The structure
      of these mouthhooks supports this fly species as being necrophagous or capable of
      producing myiasis.

PMID- 14680922
TI  - Staining methods applied to glycol methacrylate embedded tissue sections.
AB  - The use of glycol methacrylate (GMA) avoids some technical artifacts, which are
      usually observed in paraffin-embedded sections, providing good morphological
      resolution. On the other hand, weak staining have been mentioned during the use
      of different methods in plastic sections. In the present study, changes in the
      histological staining procedures have been assayed during the use of staining and
      histochemical methods in different GMA-embedded tissues. Samples of tongue,
      submandibular and sublingual glands, cartilage, portions of respiratory tract and
      nervous ganglion were fixed in 4% formaldehyde and embedded in glycol
      methacrylate. The sections of tongue and nervous ganglion were stained by H&E.
      Picrosirius, Toluidine Blue and Sudan Black B methods were applied, respectively,
      for identification of collagen fibers in submandibular gland, sulfated
      glycosaminoglycans in cartilage (metachromasia) and myelin lipids in nervous
      ganglion. Periodic Acid-Schiff (PAS) method was used for detection of
      glycoconjugates in submandibular gland and cartilage while AB/PAS combined
      methods were applied for detection of mucins in the respiratory tract. In
      addition, a combination of Alcian Blue (AB) and Picrosirius methods was also
      assayed in the sublingual gland sections. The GMA-embedded tissue sections showed
      an optimal morphological integrity and were favorable to the staining methods
      employed in the present study. In the sections of tongue and nervous ganglion, a
      good contrast of basophilic and acidophilic structures was obtained by H&E. An
      intense eosinophilia was observed either in the striated muscle fibers or in the
      myelin sheaths in which the lipids were preserved and revealed by Sudan Black B.
      In the cartilage matrix, a strong metachromasia was revealed by Toluidine Blue in
      the negatively-charged glycosaminoglycans. In the chondrocytes, glycogen granules
      were intensely positive to PAS method. Extracellular glycoproteins were also PAS
      positive in the basal membrane and in the region occupied by the lamina externa
      and reticular fibers surrounding each smooth muscle cells of the blood vessels.
      In the epithelial cells of the respiratory tract, acid and neutral mucins were
      histochemically detected by AB and PAS methods, respectively. Moreover, granules
      containing acid and neutral mucins were revealed in purple by AB and PAS
      concomitantly. In the sublingual gland sections, a distinct affinity of acid
      mucins by AB (in turquoise-blue) and collagen fibers by Picrosirius (in red) was
      obtained when these methods were combined. Although some routine dyes used in
      paraffin sections have showed a weak stain in historesin sections, our results
      showed that different dyes could be applied in GMA sections if modified staining
      procedures were assayed. Therefore, appropriate staining contrast and, thus,
      detection of one or different substances in a same section can be acquired in
      association to the good morphological resolution provided by GMA.

PMID- 14680923
TI  - Observations of the intestinal mucosa using environmental scanning electron
      microscopy (ESEM); comparison with conventional scanning electron microscopy
      (CSEM).
AB  - In order to evaluate the potential use of environmental scanning electron
      microscopy (ESEM) in biology, structural changes of the jejunal villi of rats
      were studied after periods of fasting and refeeding, using a conventional
      scanning electron microscope (CSEM) and ESEM. While observation using the CSEM,
      involves chemical fixation, drying and coating, observation of fresh, unprepared
      materials can be directly realized with the ESEM. Environmental microscopy
      provides a relatively new technology for imaging hydrated materials without
      specimen preparation and conductive coating. Direct observation of biological
      samples in their native state is therefore possible with an ESEM. After fasting,
      the jejunal mucosa is dramatically reduced in size, splits and holes appearing at
      the tip of the villi. These changes were observed whatever the type of technique
      used. Artifacts due to the sample preparation for CSEM observation (drying,
      coating) can therefore be excluded. However, CSEM and ESEM must be used jointly.
      While, CSEM must be preferred for surface analysis involving high magnifications,
      ESEM observation, on the other hand, can prove valuable for determining the
      living aspect of the samples.

PMID- 14680924
TI  - Diethylcarbamazine induces loss of microfilarial sheath of Wuchereria bancrofti.
AB  - Light microscopy analyses of microfilariae of Wuchereria bancrofti treated with
      DEC revealed a striking loss of the microfilarial sheath. However, no effect was
      observed on microfilariae of Litomosoides chagasfilhoi treated with DEC. For
      quantitative analyses microfilariae of W. bancrofti were processed for SEM.
      Controls, which have not received DEC, had 29.8% of exsheathed microfilariae.
      Conversely, the number of exsheathed microfilariae increased as increased DEC
      concentrations: 5 microg/ml (75.9%), 10 microg/ml (80.1%), and 50 microg/ml
      (87.7%). After DEC treatment some of sheathed microfilariae showed a wrinkled
      surface, and in some microfilariae, sheaths were observed being liberated almost
      intact from the larvae surface. But, frequently residues of the lost sheath over
      the surface were also observed. No damage was observed in the microfilariae
      cuticle. The present work shows quantitative data on the loss of the
      microfilarial sheath of W. bancrofti after treatment with DEC. Since no loss of
      microfilarial sheath was observed in microfilariae of L. chagasfilhoi submitted
      to the same conditions, DEC may present different mechanisms of action for
      distinct filarial species.

PMID- 14680925
TI  - Cytochemical localization of calcium and X-ray microanalysis of Catharanthus
      roseus L. infected with phytoplasmas.
AB  - The potassium pyroantimonate (KPA) Ca(2+) precipitation technique, X-ray
      microanalysis and Electron Energy Loss Spectroscopy carried out by transmission
      electron microscopy were used to analyze the Ca(2+) distribution in Catharanthus
      roseus L. leaves infected with phytoplasmas belonging to different taxonomic
      groups, and in phytoplasma cells. The analysis revealed that the distribution of
      Ca(2+) was different in healthy and diseased plants (where the KPA deposits were
      numerous) and no differences were observed in the tissues of the three types of
      infected C. roseus L. Since no KPA precipitates were visible in the phloem and on
      phytoplasma cells, it is likely that Ca(2+) ions are not directly involved in
      phytoplasma replication, but, in infected cells is a response to the pathogen
      indicative of a higher Ca(2+) in the plasmalemma.

PMID- 14680926
TI  - A structural study of the retinal photoreceptor, plexiform and ganglion cell
      layers following exposure to UV-B and UV-C radiation in the albino rat.
AB  - Over the last two decades, ultraviolet radiation levels (UV), reaching the
      Earth's surface, have been increasing at a rate of 1.5% per each 1% loss of the
      ozone layer. Moreover, artificial UV-sources have also proliferated and
      contributed to the rising UV-stress that many organisms have to face. To assess
      how the vertebrate retina responds to an exposure of short wavelength UV, we
      focused our attention on the rat retina, observing photoreceptor (containing
      outer and inner segments of rods and cones), inner plexiform, and ganglion cell
      layers by light and transmission electron microscopy using conventional and
      cytochemical techniques. We analyzed how cells of the layers in question
      responded to a 30 min exposure to UV-C and UV-B radiation with doses of 7200 and
      590 J/cm(2), respectively. The results show that there are significant changes in
      the nuclei and cytoplasmic organelles of the exposed retinae when compared with
      those of the unexposed controls. The changes include an increase in
      heterochromatin, distension of rough endoplasmic reticulum, mitochondrial
      disruptions, and increases in the number of myelin bodies. The recorded
      morphological changes, especially those of the ganglion cells, are suggestive of
      apoptotic processes and show that the exposure of vertebrate retina to
      wavelengths ranging from 254 to 312 nm can produce alterations that are likely to
      impact negatively on the retina's proper functioning.

PMID- 14680927
TI  - Structure and distribution of antennal sensilla of the red imported fire ant.
AB  - The morphology of the antenna of the red imported fire ant, Solenopsis invicta,
      was examined by light microscopy, scanning electron microscopy, and transmission
      electron microscopy. The antennae are sexually dimorphic: the worker antenna has
      porous sensilla on the two distal segments (the antennal club), whereas the
      clubless male antenna has porous sensilla on all segments past the pedicel. The
      major type of porous sensilla on both male and female is sensilla tricodea
      curvata. However, the male s. tricodea curvata are rather uniform in size,
      whereas the female s. tricodea curvata vary considerably in thickness. The number
      of sensilla on the distal segment of the worker antenna increases with segment
      length. This suggests a possible mechanism by which task assignments in S.
      invicta could be determined by the presence or absence of sensilla sensitive to
      specific task-related odor or pheromone cues. The sensilla basiconica have an
      invariant spatial pattern on worker and queen antennae.

PMID- 14680928
TI  - GAP-43 mRNA detection by in situ hybridization, direct and indirect in situ RT
      PCR in hippocampal and cerebellar tissue sections of adult rat brain.
AB  - The growth-associated protein GAP-43 is a presynaptic membrane phosphoprotein
      that is expressed at high levels during development and axonal growth. To
      evaluate the cellular distribution of GAP-43 mRNA in the hippocampus and
      cerebellum of adult rats we applied in situ hybridization (ISH) as well as direct
      and indirect in situ RT-PCR using biotin as a reporter molecule. ISH resulted in
      a positive signal in most cerebellar granular cells and in 30% of hippocampal CA3
      neurons. Direct in situ RT-PCR yielded cells with strong signals in every region
      investigated, with elevated background levels most likely related to
      incorporation of labeled nucleotides into non-specific amplicons through internal
      priming and DNA repair activity. Indirect in situ RT-PCR turned out to be the
      best approach for detecting GAP-43 mRNA positive cells. Cerebellar cells
      exhibiting a positive signal for GAP-43 mRNA were of the granular cell type
      (98%). Hippocampal neurons with a positive reaction for GAP-43 mRNA included all
      the neuron groups analyzed, namely CA1 (99%) and CA3 pyramidal cells (94%) and
      dentate gyrus granule cells (92%). Dentate gyrus granule cells have not tested
      positive for GAP-43 mRNA detection by molecular morphology analysis. These data
      show that in normal rats GAP-43 mRNA is present in different cell populations of
      hippocampal formation, supporting the role of this protein in the ongoing
      processes of synaptic plasticity.

PMID- 14680929
TI  - Image analysis of tendon helical superstructure using interference and polarized
      light microscopy.
AB  - Wave-like structures (WLS also known as crimp) have generally been reported to be
      planar structures. However, there is evidence that a helical superstructure,
      rather than a planar one, should be considered. Conditions dictated by
      supramolecular chemistry, molecular recognition and self-assembly favor the idea
      of a helical arrangement for collagen bundles in a supramolecular structure. The
      aim of this work is to provide additional data in support of a helical
      superstructure for collagen bundles in tendons. Cryosections of fixed flexor
      bovine tendons and sections of resin-embedded peeled rat tail were studied using
      polarized light, interference, and phase contrast microscopy. Image analysis was
      used to find appropriate mathematical descriptors for WLS. Interference colors
      due to the dispersion of birefringence allowed the detection of a gradual,
      intertwined twisted fiber organization in WLS, as the angle of the tendon axis
      was rotated relative to the polarizers. Helical movements of the images of the
      WLS bands were produced using animation methods. Interference microscopy revealed
      interference colors associated with different orientations and dry mass
      concentrations in the fibers, especially in tendon cross-sections, which also
      exhibited Maltese-cross birefringence images. Similar images were detected by
      interference microscopy, suggesting a spiral organization of fibers in the
      section plane. The helical orientation of the fibers was detected by focusing
      through different planes of sections. Based on a comparison of this
      superstructure with mesophases, the twisted grain boundary concept is considered
      to be the most appropriate for the classification of tendon WLS.

PMID- 14680930
TI  - The structure of a metallic glass system using EXELFS and EXAFS as complementary
      probes.
AB  - The short-range atomic order around all three constituent atoms in a prototypical
      bulk metallic glass (BMG) system was probed in a complementary way, using
      extended X-ray absorption fine structure for neighborhood of the higher atomic
      number elements, and extended energy loss fine structure (EXELFS) for the lower
      atomic number ones. The Pd(x)Ni((80-x))P((20)) system is a prototype for a whole
      class of BMG formers which are 80% transition metal and 20% metalloid. We find
      that the structure of these BMGs could be explained in terms of those of glasses
      at the end of the BMG range, namely, Pd(60)Ni(20)P(20) and Pd(30)Ni(50)P(20). The
      binary phosphide crystals near [Formula: see text] and 80 are found to be
      simulate very well the local atomic structure of Pd(30)Ni(50)P(20) and
      Pd(60)Ni(20)P(20) glasses, respectively. The best glass former in this series,
      Pd(40)Ni(40)P(20), is best described by a weighted average of Pd(30)Ni(50)P(20)
      and Pd(60)Ni(20)P(20) structures.

PMID- 14680931
TI  - Imaging of human meiotic chromosomes by scanning near-field optical microscopy
      (SNOM).
AB  - Centromeres and telomeres are key structures of mitotic and meiotic chromosomes.
      Especially telomeres develop particular structural properties at meiosis. Here,
      we investigated the feasibility of scanning near-field optical microscopy (SNOM)
      for light-microscopic imaging of meiotic telomeres in the sub-hundred nanometer
      resolution regime. SNOM was applied to visualise the synaptonemal complex (SC)
      and telomere proteins (TRF1, TRF2) after differential immuno-fluorescent
      labelling. We tested and compared two different preparation protocols for their
      applicability in a SNOM setting using micro-fabricated silicon nitride aperture
      tips. Protocol I consisted of differential labelling of meiotic chromosome cores
      (SC) by SCP3 immuno-fluorescence and telomeres by TRF1 or TRF2 immuno
      fluorescence, while protocol II combined absorption labelling with alkaline
      phosphatase substrates of cores with fluorescent labelling of telomeres. The
      results obtained indicate that protocol I reveals a better visualisation of
      structural (topographic) details than protocol II. By means of SNOM, meiotic
      chromosome cores could be visualised at a resolution overtopping that of far
      field light microscopy.

PMID- 14680932
TI  - Prestomal teeth of some flies of medical importance.
AB  - Comparison of prestomal teeth of adult Chrysomya megacephala, Chrysomya
      rufifacies, Chrysomya nigripes, Lucilia cuprina, Parasarcophaga dux and Musca
      domestica was accomplished by use of scanning electron microscopy. The prestomal
      teeth of C. megacephala, C. rufifacies, L. cuprina and P. dux are all similar in
      appearance in having various degrees of bifurcation at their tips. In contrast,
      the tips of the prestomal teeth in C. nigripes are very shallowly serrated, but
      are comparatively more deeply serrated in M. domestica. These features may help
      account for the roles these flies may play in matters of medical or veterinary
      importance, such as causing physical irritation or acting as vectors of disease
      agents.

PMID- 14680933
TI  - Scale-up of the fermentation and purification of the recombinant heavy chain
      fragment C of botulinum neurotoxin serotype F, expressed in Pichia pastoris.
AB  - A recombinant heavy chain fragment C of botulinum neurotoxin serotype F
      (BoNTF(Hc)) has been expressed in Pichia pastoris for use as an antigen in a
      proposed human vaccine. P. pastoris cells were grown using glycerol batch,
      glycerol fed-batch, and methanol fed-batch methods to achieve high cell
      densities. The total cellular protein recovered after homogenization was 72 mg/g
      of cell paste. BoNTF(Hc) was purified from soluble Pichia cell lysate employing
      ion-exchange chromatographic (IEC) and hydrophobic interaction chromatographic
      (HIC) methods developed at the bench scale using 10-100 mL columns. The process
      was performed at the pilot scale using 1-4L columns for evaluation of scale up.
      The purification process resulted in greater than 98% pure product consisting of
      at least three forms of BoNTF(Hc) based on mass spectrometry and yielded up to
      205 mg/kg cells at the bench scale and 170 mg/kg cells at the pilot scale. Full
      length BoNTF(Hc) is present based on mass spectrometry and SDS-PAGE, however is
      postulated to be N-terminally blocked by acetylation. N-terminal sequencing
      showed that two of the three forms are missing the first 11 (80%) and 14 (20%)
      amino acids of the N-terminus from the full-length form. The ratios of the two
      clipped forms were consistent from the bench to pilot scales. Purified BoNTF(Hc)
      at the pilot scale was found to sufficiently protect mice against a high dose of
      BoNTF neurotoxin.

PMID- 14680934
TI  - Expression of hepatitis B surface antigen in tobacco cell suspension cultures.
AB  - Hepatitis B virus ' s ' gene coding for surface antigen was cloned into plant
      transformation vectors pHER100 and pHBs100 with and without endoplasmic reticulum
      retention signal, respectively. Transformed tobacco cell lines were analyzed for
      the integration of the transgene by PCR and Southern blot hybridization.
      Expression levels as determined by ELISA showed maximum expression levels of 2
      microg HBsAg gm(-1) fresh weight and 10 ng mL(-1) of spent medium in pHER100
      transformed cells. Western blot analysis confirmed the presence of 24 kDa band
      specific to HBsAg in the transformed cells. HBsAg was expressed both as
      intracellular and secreted forms in pHER100 transformed cells. The buoyant
      density in CsCl of HBsAg derived from pHBs100 transformed tobacco cells was
      determined and found to be 1.095 g mL(-1). HBsAg obtained from transformed
      tobacco cells is similar to the human serum derived one in buoyant density
      properties. This is the first report on the secretion of HBsAg particles by plant
      cells into the cell culture medium.

PMID- 14680935
TI  - Overexpression and purification of recombinant membrane PsbH protein in
      Escherichia coli.
AB  - In this work, we featured an expression system that enables the production of
      sufficient quantities ( approximately mg) of low molecular weight membrane
      protein of photosystem II, PsbH protein, for solid-state NMR as well as other
      biophysical studies. PsbH gene from cyanobacterium Synechocystis sp. PCC 6803 was
      cloned into a plasmid expression vector, which allowed expression of the PsbH
      protein as a glutathione-S transferase (GST) fusion protein in Escherichia coli
      BL21(DE3) cells. A relatively large GST anchor overcomes foreseeable problems
      with the low solubility of membrane proteins and the toxicity caused by protein
      incorporation into the membrane of the host organism. As a result, the majority
      of fusion protein was obtained in a soluble state and could be purified from
      crude bacterial lysate by affinity chromatography on immobilized glutathione
      under non-denaturing conditions. The PsbH protein was cleaved from the carrier
      protein with Factor Xa protease and purified on DEAE-cellulose column with yields
      of up to 2.1 microg protein/ml of bacterial culture. The procedure as we
      optimized is applicable for isolation of small membrane proteins for structural
      studies.

PMID- 14680937
TI  - Purification and characterization of 2'aminobiphenyl-2,3-diol 1,2-dioxygenase
      from Pseudomonas sp. LD2.
AB  - Carbazole is a nitrogen-containing heteroaromatic compound that occurs as a
      widespread and mutagenic environmental pollutant. The 2'aminobiphenyl-2,3-diol
      1,2-dioxygenase involved in carbazole degradation was purified to near
      electrophoretic homogeneity from Pseudomonas sp. LD2 by a combination of ion
      exchange chromatography, ammonium sulfate precipitation, and hydrophobic
      interaction chromatography. This purification was challenging due to the great
      instability of the enzyme under many standard conditions. The enzyme was also
      purified to electrophoretic homogeneity from recombinant Escherichia coli
      expressing the 2'aminobiphenyl-2,3-diol 1,2-dioxygenase-encoding gene cloned from
      Pseudomonas sp. LD2. The molecular mass of the native enzyme was determined by
      gel filtration to be 70 kDa. The subunit molecular masses were determined to be
      25 and 8 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
      indicating that the dioxygenase is an [alpha2beta2] heterotetramer. The optimal
      temperature and pH for the enzymatic production of 2-hydroxy-6-oxo-6-phenylhexa
      2,4-dienoic acid (HOPDA) from 2,3-dihydroxybiphenyl were determined to be 40
      degrees C and 8.0, respectively. The maximum observed specific activity on 2,3
      dihydroxybiphenyl was 48.1 mmol HOPDA min(-1) mg(-1). This indicated a maximum
      observed turnover rate of 360,000 molecules HOPDA enz(-1) s(-1). The K'm
      inhibition constant Ks and Vmax on 2,3 dihydroxybiphenyl were determined to be 5
      microM, 37 microM, and 44 mmol min(-1) mg(-1), respectively. These results show
      that 2'aminobiphenyl-2,3-diol 1,2-dioxygenase is a meta-cleavage enzyme related
      to the 4,5-protocatechuate dioxygenase family, with comparable purification
      challenges posed by intrinsic enzyme instability.

PMID- 14680936
TI  - High-level expression, purification, and characterization of porcine somatotropin
      in Pichia pastoris.
AB  - Porcine somatotropin (pST) significantly improves the growth rate, carcass
      composition, and growth efficiency of pigs while reducing feed consumption and
      fat deposition. Pichia pastoris was used as a host to efficiently express the pST
      gene in this study. Up to 90% of the recombinant protein was secreted into the
      culture medium, yielding about 900 mg/L rpST in shake-flask cultures. SDS-PAGE
      and Western blot analyses showed that rpST migrated as a single band with a
      molecular weight of approximately 25 kDa, and had the same immunoreactivity as
      native pST. The culture supernatant of our rpST expression strain, X
      33/pPICZalphaA-pST/9, was purified to greater than 95% homogeneity with 71.4%
      recovery using ammonium sulfate precipitation, Sephadex G-25 Fine desalting, and
      Q Sepharose High Performance Ion Exchange chromatography. MALDI-TOF-MS
      demonstrated a molecular mass of 21,771Da for rpST, close to its predicted size.
      Isoelectric focusing electrophoresis results from three batches of purified rpST
      consistently showed a pI value between 4.55 and 5.2. Purified rpST was able to
      promote Nb2 cell proliferation and reduce feed intake of crossbred gilts, a type
      of pig breed, with no decrease in body weight gain when administered by
      injection. These results indicate that the P. pastoris expression system will be
      useful for production of bioactive rpST at commercially relevant levels.

PMID- 14680938
TI  - Purification of castamollin, a novel antifungal protein from Chinese chestnuts.
AB  - A novel antifungal protein, designated castamollin, was isolated from Chinese
      chestnut (Castanea mollisima) seeds with a procedure involving ion exchange
      chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel,
      ion exchange chromatography on CM-Sepharose and FPLC-gel filtration on Superdex
      75. Castamollin possessed a novel N-terminal sequence demonstrating little
      similarity to N-terminal sequences of Castanea sativa chitinase. Castamollin
      exhibited a molecular mass of 37kDa in gel filtration and SDS-PAGE. It inhibited
      the activity of human immunodeficiency virus-1 reverse transcriptase with an
      IC(50) of 7microM and translation in a cell-free rabbit reticulocyte lysate
      system with an IC(50) of 2.7microM. Castamollin displayed antifungal activity
      against Botrytis cinerea, Mycosphaerella arachidicola, Physalospora piricola, and
      Coprinus comatus but was devoid of lectin activity.

PMID- 14680939
TI  - Characterization of a variant of PAC-1 in large granular lymphocyte leukemia.
AB  - Phosphatase in activated T cells (PAC-1) is a mitogen-induced early responsive
      gene. It encodes a 32 kDa tyrosine-threonine dual specificity phosphatase.
      Constitutive expression of PAC-1 leads to an inhibition of MAP kinase activity in
      vivo. Such constitutive expression was reported in HTLV-1 infected cell lines. In
      the present study, we observed the constitutive over-expression of two
      transcripts related to PAC-1 in large granular lymphocyte (LGL) leukemia. By
      screening a LGL leukemia cDNA library using the 3' end of a PAC-1 probe, we
      obtained a clone (clone 8) which retains one and one half introns, excludes two
      exons, and matches one hundred percent with a DNA sequence on chromosome 2. The
      deduced amino acid sequence of the predicted protein contains 170 amino acids and
      is 144 amino acids shorter than PAC-1. When we expressed this protein in
      Escherichia coli as a GST-fusion protein, a 45 kDa (19 kDa PAC-1 variant+26 kDa
      GST protein) protein was obtained. The expressed protein was purified to near
      homogeneity by using a glutathione affinity column. The purified protein did not
      have any intrinsic phosphatase activity when assayed in vitro. But when this
      purified protein was added to a phosphatase assay system in combination with a
      recombinant dual specificity phosphatase, CL100, enhanced phosphatase activity
      was observed. The significance of the constitutive over-expression and its
      physiological role of this protein remain to be established in leukemic LGL.

PMID- 14680940
TI  - Expression and purification of a putative H-NS nucleoid-associated protein from
      the phytopathogen Xylella fastidiosa.
AB  - The H-NS protein is one of the major constituents of the nucleoid structure that
      has been implicated in the DNA packaging and in the global regulation of gene
      expression. The study of this transcriptional regulator is an effort to fight
      Xylella fastidiosa, a citrus pathogen responsible for a range of economically
      important plant diseases, including the citrus variegated chlorosis (CVC). The
      putative H-NS ORF was cloned into a pET32-Xa/LIC vector in order to overexpress
      it coupled with fusion tags in Escherichia coli BL21(DE3). The expressed
      recombinant protein was purified by immobilized metal affinity chromatography (Ni
      NTA resin) and its identity verified by mass spectrometry (MALDI-TOF). Final
      purification was performed by cation-exchange chromatography (SP Sepharose Fast
      Flow) and the purified protein was found as a single band on SDS-PAGE. The
      folding and its DNA binding activity were verified by circular dichroism and
      fluorescence spectroscopy, respectively.

PMID- 14680941
TI  - Refolding and characterization of the functional ligand-binding domain of human
      lectin-like oxidized LDL receptor.
AB  - Lectin-like oxidized low-density lipoprotein receptor (LOX-1), a type II membrane
      protein that can recognize a variety of structurally unrelated macromolecules,
      plays an important role in host defense and is implicated in atherogenesis. To
      understand the interaction between human LOX-1 and its ligands, in this study the
      functional C-type lectin-like domain (CTLD) of LOX-1 was reconstituted at high
      efficiency from inactive aggregates in Escherichia coli using a refolding
      technique based on an artificial chaperone. The CD spectra of the purified domain
      suggested that the domain has alpha-helical structure and the blue shift of Trp
      residues was observed on refolding of the domain. Like wild-type hLOX-1, the
      refolded CTLD domain was able to bind modified LDL. Thus, even though CTLD
      contains six Cys residues that form disulfide bonds, it recovered its specific
      binding ability on refolding. This suggests that the correct disulfide bonds in
      CTLD were formed by the artificial chaperone technique. Although the domain
      lacked N-glycosylation, it showed high affinity for its ligand in surface plasmon
      resonance experiments. Thus, unglycosylated CTLD is sufficient for binding
      modified LDL.

PMID- 14680942
TI  - Expression, purification, and characterization of His20 mutants of rat mevalonate
      kinase.
AB  - Mevalonate kinase plays a key role in regulating the biosynthesis of cholesterol
      in animal cells. Human mevalonate kinase His20Pro has been reported as one of the
      three common mutations in the mevalonate kinase gene in mevalonic aciduria and
      hyperimmunoglobulinemia D/periodic fever syndrome patients. His20 is also a
      highly conserved residue among all aligned mevalonate kinase sequences. To study
      the role of His20 of mevalonate kinase, a variety of mutant expression plasmids
      of rat mevalonate kinase including pRMK(H20L), pRMK(H20Y), and pRMK(H20K) were
      constructed using site-directed mutagenesis, and mutant proteins were
      overexpressed and purified. CD spectroscopy of wild-type protein and mutants
      indicated that mutations H20L and H20Y did not induce significant secondary
      structural changes. The results from kinetic studies showed that this highly
      conserved histidine is an important residue for the function of the enzyme.

PMID- 14680943
TI  - Purification of brain tubulin through two cycles of polymerization
      depolymerization in a high-molarity buffer.
AB  - Microtubules can be assembled in vitro from purified alpha/beta tubulin
      heterodimers in the presence of GTP. Tubulin is routinely obtained from animal
      brain tissue through repetitive cycles of polymerization-depolymerization,
      followed by ion-exchange chromatography to remove any contaminating microtubule
      associated proteins and motors. Here, we show that only two cycles of
      polymerization-depolymerization of pig brain tubulin in the presence of a high
      molarity PIPES buffer allow the efficient removal of contaminating proteins and
      production of a high-concentration tubulin solution. The proposed protocol is
      rapid and yields more active tubulin than the traditional ion-exchange
      chromatography-based procedures.

PMID- 14680944
TI  - High-level expression of the Arabidopsis thaliana ethylene receptor protein ETR1
      in Escherichia coli and purification of the recombinant protein.
AB  - Ethylene responses in plants are mediated by a small family of membrane integral
      receptors including the ETR1 gene product which are similar to the two-component
      bacterial histidine kinase regulators. Detailed biochemical and structural
      analysis of the ethylene-receptor family was hampered by the scarce amount of
      pure protein. Here, we report the construction, expression, and single-step
      purification of the ETR1 receptor protein from Arabidopsis thaliana in a
      bacterial expression system. The DNA fragment encoding the mature ETR1 receptor
      protein was subcloned into the pET15b expression vector and highly expressed in
      derivatives C41(DE3) and C43(DE3) of the Escherichia coli strain BL21(DE3). The
      recombinant protein was solubilised from the bacterial cells using mild non
      denaturing detergents and purified to homogeneity by Ni-NTA affinity
      chromatography, yielding approximately 2-3 mg pure protein per litre of cells.
      The molecular mass of the purified protein was estimated to be 78 kDa by SDS
      PAGE. The expression and purification of recombinant ETR1 reported here provide a
      basis for detailed functional and structural studies of the receptor protein,
      which might help to understand signal perception and signal transduction of the
      phytohormone ethylene on the molecular level.

PMID- 14680945
TI  - Characterization of recombinant and natural forms of the human LIM domain
      containing protein FHL2.
AB  - FHL2 (Four and a Half LIM domain-containing protein 2) is a member of a small
      family of proteins with four LIM domains and an N-terminal half LIM domain. It is
      an intracellular protein thought to function as an adaptor in the formation of
      multi-protein complexes involved in signaling. To obtain human FHL2 in amounts
      allowing further characterization, we evaluated different expression systems and
      chose to express FHL2 with a His6 tag in insect cells using the baculovirus
      system. The recombinant protein was highly expressed and could be purified to
      >98% homogeneity as judged by SDS-PAGE analysis. Purified recombinant FHL2 was
      used to generate antibodies allowing detection and immunoprecipitation of FHL2
      from human cells. Both recombinant and natural FHL2 were characterized by SDS
      PAGE and MALDI-TOF mass spectrometry. The molecular mass of the recombinant His6
      tagged protein obtained by mass spectrometry was 36,995Da, in good agreement with
      the apparent mass of 36kDa in SDS-PAGE and slightly higher than the 35,981Da
      calculated from the sequence of the construct. The measured molecular mass of
      natural human FHL2 was 32,742Da and the calculated mass was 32,192Da. However,
      the apparent molecular mass in SDS-PAGE is 41kDa, indicating that the natural
      protein has an abnormal electrophoretic mobility. The results show that both the
      recombinant and the natural proteins are post-translationally modified and
      indicate that such modifications may lead to an abnormal electrophoretic behavior
      of natural human FHL2.

PMID- 14680946
TI  - On-column purification and refolding of recombinant bovine prion protein: using
      its octarepeat sequences as a natural affinity tag.
AB  - Prion protein has a key role in the occurrence of transmissible spongiform
      encephalopathy (TSE) and development of these diseases. Here, we provide a
      convenient procedure for on-column purification and refolding of the full-length
      mature bovine prion protein (bPrP) from Escherichia coli using immobilized metal
      (Ni) affinity chromatography, based on the metal-binding property of its unusual
      octarepeat sequences containing six tandem copies. Following extensive washing,
      the bPrP pellet was solubilized by guanidine hydrochloride and subjected to Ni
      NTA agarose column. Purification and refolding were achieved by stepwise gradient
      washing with reduced guanidine hydrochloride concentrations. Triton X-100 and
      beta-mercaptoethanol were required in this rapid refolding process. The isolated
      prion protein was identified by monoclonal antibodies and its integrity was
      monitored by mass spectroscopy. Its correct folding was confirmed from circular
      dichroism (CD) experiments. Moreover, thioflavin T-binding assay showed that the
      recombinant bPrP could be transformed into amyloid fiber structures like that of
      the infectious prion isoform PrP(sc).

PMID- 14680947
TI  - Optimized gene synthesis and high expression of human interleukin-18.
AB  - Human interleukin-18 (hIL-18), originally known as an IFN-gamma-inducing factor,
      is a recently cloned cytokine that is secreted by Kupffer cells of the liver and
      by stimulated macrophages. We have previously established a method of expression
      and purification of IL-18. The yield however remains low and the insufficient
      expression of a heterologous protein could be due to skewed codon usage between
      the expression host and the cDNA donor. The sequence of mature hIL-18 has 37 a.a.
      rare codons for Escherichia coli in a total of 157 a.a. To overcome this problem,
      gene synthesis was performed with optimized codons for the expression host E.
      coli. The final yield of the hIL-18 protein with optimized codons was about five
      times higher than the yield with the native sequence. Using a minimal medium,
      this system produces large quantities of labeled proteins that can be used in NMR
      analysis. Our simple and efficient production system can be applied to the
      production of other cytokines for new structural and therapeutic use.

PMID- 14680948
TI  - Expression, purification, and inhibitory activities of mouse cytotoxic T
      lymphocyte antigen-2alpha.
AB  - Cytotoxic T-lymphocyte antigen-2 (CTLA-2) is a novel cysteine proteinase
      inhibitor. The protein sequence is homologous to the proregion of mouse cathepsin
      L. Here, we report the expression, purification, and characterization of
      recombinant CTLA-2 (CTLA-2alpha). CTLA-2alpha was cloned into the pET16b vector
      and the plasmid was transformed into Escherichia coli strain BL21 (DE3) pLysS.
      The recombinant CTLA-2alpha was highly expressed and purified by His-Bind
      affinity chromatography, Factor Xa digestion, and hydrophobic chromatography.
      Throughout these procedures, 3mg recombinant CTLA-2alpha was obtained from 450 ml
      of bacterial culture medium. The purified protein exhibited inhibitory activities
      towards certain cysteine proteinases and was properly refolded, as indicated by
      circular dichroism spectroscopy. Recombinant CTLA-2alpha fully inhibited Bombyx
      cysteine proteinase (BCP) (overall Kd (Ki*) = 0.23 nM) and and cathepsin L
      (overall Kd (Ki*) = 0.38 nM). Inhibition of cathepsin H ( Ki = 86 nM) and papain
      ( Ki = 560 nM) was much weaker, while inhibition of cathepsin B was negligible (
      Ki > 1 microM). Our results indicate that mouse CTLA-2alpha is a selective
      inhibitor of the cathepsin L-like cysteine proteinases.

PMID- 14680949
TI  - Purification of recombinant human growth hormone from CHO cell culture
      supernatant by Gradiflow preparative electrophoresis technology.
AB  - Purification of recombinant human growth hormone (rhGH) from Chinese hamster
      ovary (CHO) cell culture supernatant by Gradiflow large-scale electrophoresis is
      described. Production of rhGH in CHO cells is an alternative to production in
      Escherichia coli, with the advantage that rhGH is secreted into protein-free
      production media, facilitating a more simple purification and avoiding
      resolubilization of inclusion bodies and protein refolding. As an alternative to
      conventional chromatography, rhGH was purified in a one-step procedure using
      Gradiflow technology. Clarified culture supernatant containing rhGH was passed
      through a Gradiflow BF200 and separations were performed over 60 min using three
      different buffers of varying pH. Using a 50 mM Tris/Hepes buffer at pH 7.5
      together with a 50 kDa separation membrane, rhGH was purified to approximately
      98% purity with a yield of 90%. This study demonstrates the ability of Gradiflow
      preparative electrophoresis technology to purify rhGH from mammalian cell culture
      supernatant in a one-step process with high purity and yield. As the Gradiflow is
      directly scalable, this study also illustrates the potential for the inclusion of
      the Gradiflow into bioprocesses for the production of clinical grade rhGH and
      other therapeutic proteins.

PMID- 14680950
TI  - Purification of antibody Fab and F(ab')2 fragments using Gradiflow technology.
AB  - The Gradiflow, a preparative electrophoresis instrument designed to separate
      molecules on the basis of their size and charge, was used to purify antibody Fab
      and F(ab')2 fragments. The method described is charge based, utilizing the
      difference in the pI between the antibody Fab/F(ab')2 fragments and antibody Fc
      fragments that occur after enzyme digestion of whole antibody molecules. This
      method of purification was successful across a range of monoclonal and polyclonal
      antibodies. In particular, F(ab')2 fragments were purified from a number of mouse
      monoclonal antibodies (both IgG1 and IgG2a isotypes) and Fab fragments were
      purified from egg yolk IgY polyclonal antibodies. This is a rapid purification
      method which has advantages over alternative methods that usually comprise ion
      exchange and gel filtration chromatography. This method may be applicable to most
      antibody digest preparations.

PMID- 14680951
TI  - Human pituitary glutaminyl cyclase: expression in insect cells and dye affinity
      purification.
AB  - Human pituitary glutaminyl cyclase (hQC) was expressed in Drosophila S2 cells
      under the control of an inducible metallothionene promoter and fused to the
      Drosophila immunoglobulin-binding protein signal sequence to enable secretion
      into the culture media. Expression levels reached 50 microg/mL culture media
      after 7 days of induction. The enzyme was purified to homogeneity directly from
      culture media by affinity chromatography on Reactive Blue 4-agarose using a step
      pH elution. The identity of the expressed protein was confirmed by peptide mass
      mapping and Western blotting. Glutaminyl cyclase was expressed as a fully active
      37 kDa enzyme with kcat/Km values of 14.3, 9.3, and 2.4 mM(-1)s(-1) for the
      substrates Gln-Gln, Gln-NH(2), and Gln-t-butyl ester, respectively. The two
      cysteines were disulfide bonded, and the lone predicted glycosylation site,
      asparagine 49, was shown by both enzymatic deglycosylation of the expressed
      enzyme and site-directed mutagenesis to be glycosylated.

PMID- 14680953
TI  - kappa-Carrageenan as a carrier in affinity precipitation of yeast alcohol
      dehydrogenase.
AB  - kappa-Carrageenan is a non-toxic polymer from seaweeds, which becomes reversibly
      insoluble upon the addition of K(+). Its conjugate with the dye, Cibacron Blue
      3GA, was used to purify alcohol dehydrogenase from crude yeast extract by
      affinity precipitation. Response surface methodology was used to optimize
      conditions for affinity precipitation of the enzyme with the polymer-dye
      conjugate. Recovery of 58% of the enzyme activity with 13.6-fold purification was
      obtained.

PMID- 14680952
TI  - Affinity purification of antibodies by using Ni2+-resins on which inclusion body
      forming proteins are immobilized.
AB  - Bacterially expressed recombinant proteins are widely used for producing specific
      antibodies. Unfortunately, many recombinant proteins are recovered as insoluble
      materials, so-called inclusion bodies. Inclusion bodies are rather advantageous
      from a point of view of immunogens because fairly pure proteins can be feasibly
      extracted from the inclusion bodies. However, we encounter a problem with an
      insoluble protein when we make an antigen-immobilized column for affinity
      purification of antibodies because we need a soluble protein in usual
      immobilization methods. Histidine-tagged proteins can be bound to Ni(2+)-resins
      in buffer containing 6M guanidine-HCl, in which most insoluble proteins are
      solubilized. Taking advantage of this feature, we have successfully purified
      antigen-specific antibodies by directly using Ni(2+)-resins onto which denatured
      proteins are bound.

PMID- 14680954
TI  - Expression and purification of Src I from sea anemone Sagartia rosea as a
      recombinant non-fusion protein.
AB  - The cDNA coding for an acidic actinoporin, Sagartia rosea cytolysin I (Src I),
      has been isolated, cloned into pGEM-T Easy Vector, and sequenced. The region
      encoding matured Src I was also cloned into prokaryotic expression vector pBV220
      and expressed in Escherichia coli as a non-fusion protein in the form of
      inclusion body. Through washing and denaturation-renaturation step, the
      recombinant Src I was purified by Q Sepharose Fast Flow ion exchange
      chromatography and Phenyl Sepharose hydrophobic interaction chromatography. The
      two-step purification of Src I was effective, simple, and suitable for isolating
      large amount of high purity (above 95%) recombinant Src I.

PMID- 14680955
TI  - In vitro protein refolding by chromatographic procedures.
AB  - In vitro protein refolding is still a bottleneck in both structural biology and
      in the development of new biopharmaceuticals, especially for commercially
      important polypeptides that are overexpressed in Escherichia coli. This review
      focuses on protein refolding methods based on column procedures because recent
      advances in chromatographic refolding have shown promising results.

PMID- 14680956
TI  - An improved purification procedure for soluble processing alpha-glucosidase I
      from Saccharomyces cerevisiae overexpressing CWH41.
AB  - Processing alpha-glucosidase I, which is encoded by CWH41, regulates one of the
      key steps in asparagine-linked glycoprotein biosynthesis by cleaving the terminal
      alpha-1,2-linked glucose from Glc(3)Man(9)GlcNAc(2), the common oligosaccharide
      precursor. This cleavage is essential for further processing of the
      oligosaccharide to the complex, hybrid, and high mannose type carbohydrate
      structures found in eukaryotes. A method is described for the purification of the
      soluble form of the alpha-glucosidase I, from recombinant Saccharomyces
      cerevisiae overexpressing CWH41. A homogeneous enzyme preparation was obtained in
      higher yield than previously reported. Cultivation of recombinant S. cerevisiae
      in a fermenter increased the biomass 1.7 times per liter and enzyme production 2
      times per liter compared to cultivation in shake flasks. Ammonium sulfate
      precipitation with three chromatography steps, including chromatography on an N
      (5'-carboxypentyl)-1-deoxynojirimycin column, resulted in highly purified enzyme
      with no detectable contamination by other alpha- and beta-aryl-glycosidases. The
      purification procedure reproducibly yielded 40 microg of pure enzyme per gram wet
      biomass. Enzyme that was purified using an alternative procedure contained minor
      impurities and was hydrolyzed by an endogenous proteolytic activity to peptides
      that retained full catalytic activity. Controlled trypsin hydrolysis of the
      highly purified enzyme released polypeptide(s) containing the alpha-glucosidase I
      catalytic domain, with no loss of catalytic activity. This suggests that the
      catalytic domain of yeast alpha-glucosidase I is resistant to trypsin hydrolysis
      and remains fully functional after cleavage.

PMID- 14680957
TI  - In vitro uridylylation of the Azospirillum brasilense N-signal transducing GlnZ
      protein.
AB  - Azospirillum brasilense is a diazotroph which associates with important
      agricultural crops. The nitrogen fixation process in this organism is highly
      regulated by ammonium and oxygen, and involves several proteins including the two
      PII-like proteins, GlnB and GlnZ. Although these proteins are structurally very
      similar, they play different roles in the control of nitrogen fixation. In this
      work, we describe the expression, purification, and uridylylation of the GlnZ
      protein of A. brasilense strain FP2. The amplified glnZ gene was sub-cloned and
      expressed as a His-tagged fusion protein. After purification, we obtained 30-40
      mg of purified GlnZ per liter of culture. This protein was purified to 99% purity
      and assayed for in vitro uridylylation using a partially purified Escherichia
      coli GlnD as a source of uridylylyl-transferase activity. Analyses of the
      uridylylation reactions in non-denaturing and denaturing polyacrylamide gel
      electrophoresis showed that up to 74% of GlnZ monomers were modified after 30 min
      reaction. This covalent modification is strictly dependent on ATP and 2
      ketoglutarate, while glutamine acts as an inhibitor and promotes deuridylylation.

PMID- 14680958
TI  - Cloning, expression, and purification of glyoxysomal 3-oxoacyl-CoA thiolase from
      sunflower cotyledons.
AB  - The glyoxysomal beta-oxidation system in sunflower (Helianthus annuus L.)
      cotyledons is distinguished by the coexistence of two different thiolase
      isoforms, thiolase I and II. So far, this phenomenon has only been described for
      glyoxysomes from sunflower cotyledons. Thiolase I (acetoacetyl-CoA thiolase, EC
      2.3.1.9) recognizes acetoacetyl-CoA only, while thiolase II (3-oxoacyl-CoA
      thiolase, EC 2.3.1.16) exhibits a more broad substrate specificity towards 3
      oxoacyl-CoA esters of different chain length. Here, we report on the cloning of
      thiolase II from sunflower cotyledons. The known DNA sequence of Cucumis sativus
      3-oxoacyl-CoA thiolase was used to generate primers for cloning the corresponding
      thiolase from sunflower cotyledons. RT-PCR was then used to generate an internal
      fragment of the sunflower thiolase gene and the termini were isolated using 5'-
      and 3'-RACE. Full-length cDNA was generated using RT-PCR with sunflower thiolase
      specific primers flanking the coding region. The resultant gene encodes a
      thiolase sharing at least 80% identity with other plant thiolases at the amino
      acid level. The recombinant sunflower thiolase II was expressed in a bacterial
      system in an active form and purified to apparent homogeneity in a single step
      using Ni-NTA agarose chromatography. The enzyme was purified 53.4-fold and had a
      specific activity of 235 nkat/mg protein. Pooled fractions from the Ni-NTA column
      resulted in an 83% yield of active enzyme to be used for further
      characterization.

PMID- 14680959
TI  - Expression and purification of the recombinant SALT lectin from rice (Oryza
      sativa L.).
AB  - The SALT protein is a 14.5 kDa mannose-binding lectin, originally described as
      preferentially expressed in rice plant roots in response to NaCl stress.
      Recombinant SALT lectin was produced in Escherichia coli from a cDNA clone
      encoding protein. After isopropyl-beta-d-thiogalactopyranoside induction, the
      expression level achieved was 23% of the soluble protein. The recombinant
      agglutinin was purified by a single-step process by dialyses against a high
      concentrated salt solution. After purification, hemagglutination assays of rabbit
      erythrocytes revealed that the recombinant SALT protein is a potent agglutinin
      (0.078 microg ml(-1) minimal concentration). The purified recombinant lectin was
      also used for comparative estimation of native protein amounts in protein
      extracts from rice plants by Western blot assay.

PMID- 14680960
TI  - The Nano-tag, a streptavidin-binding peptide for the purification and detection
      of recombinant proteins.
AB  - We present a new streptavidin-binding peptide for both the purification and the
      detection of recombinant proteins. The peptide possesses nanomolar-affinity for
      streptavidin and therefore was termed Nano-tag. The Nano-tag(15) is 15 amino
      acids long and binds to streptavidin with a dissociation constant of 4 nM and the
      Nano-tag(9) is a 9-mer peptide with a dissociation constant of 17 nM. We
      demonstrate the one-step purification of Nano-tagged proteins, namely bovine
      heart fatty acid-binding protein (FABP), bacterial chloramphenicol
      acetyltransferase (CAT), and green fluorescent protein (GFP), from an in vitro
      translation system as well as from an Escherichia coli lysate. No significant
      influence of the Nano-tag(15) and of the conditions during affinity
      chromatography on maturation or activity of the proteins was observed whereas the
      Nano-tag(9) revealed a slight decline in the amount and activity of the
      synthesized proteins. The main advantage of the Nano-tag is the mild and specific
      elution with washing buffer plus biotin or related compounds, which enables the
      elution of the bound fusion protein from the streptavidin column in the native
      state. Additionally, the Nano-tag allowed the detection of recombinant proteins
      on Western blots by a streptavidin-alkaline phosphatase conjugate.

PMID- 14680961
TI  - The class C acid phosphatase of Helicobacter pylori is a 5' nucleotidase.
AB  - The results from purification and characterization studies of the hppA gene
      product of Helicobacter pylori confirm its identification as a class C acid
      phosphatase. The hppA gene of H. pylori ATCC strain 49503 was amplified and
      modified by PCR, cloned into pET21b, and overexpressed in Escherichia coli. The
      recombinant protein was liberated from membranes and purified (16x) to apparent
      homogeneity with cation exchange and Ni-chelate chromatography resulting in a
      recovery of 39% of total starting activity. The recombinant acid phosphatase
      exhibited a denatured molecular mass of 24 kDa by SDS-PAGE. Phosphatase activity
      in both crude and purified samples could be renatured and detected after SDS
      PAGE. The native molecular mass of recombinant enzyme was approximately 72 kDa by
      gel filtration chromatography on Superdex 75. While phosphate and tartrate had
      little effect on phosphatase activity, molybdate, vanadate, and EDTA had
      significant inhibitory effects on enzymatic activity. Phosphomonoesterase
      activity for hydrolysis of p-nitrophenylphosphate (pNPP) as well as other
      substrates was enhanced in the presence of divalent cations including Cu(2+),
      Ni(2+), Co(2+), and Mg(2+). Recombinant HppA had narrow substrate specificity
      with highest activity for arylphosphates and significant activity for 5'
      nucleoside monophosphates. The pH optimum for enzyme activity was 4.6 and 5.2 for
      purine and pyrimidine 5' monophosphates, respectively. The affinity constants for
      the 5' nucleoside monophosphates were found to be 0.5-1 mM. Results from this
      study confirm HppA inclusion in the class C acid phosphatases and led to its
      identification as a 5' nucleotidase.

PMID- 14680962
TI  - Expression, purification, and characterization of BsSco, an accessory protein
      involved in the assembly of cytochrome c oxidase in Bacillus subtilis.
AB  - The studies described here were performed to characterize further the plasma
      membrane associated protein BsSco, which is the product of the gene ypmQ, in
      Bacillus subtilis. BsSco is a member of the Sco family of proteins found in the
      inner mitochondrial membrane of yeast and humans and implicated as an accessory
      protein in the assembly of the Cu(A) site of cytochrome c oxidase. We have cloned
      the gene expressing BsSco, placed a six-histidine tag on its C-terminus, and over
      expressed this protein in B. subtilis. Recombinant BsSco with the his-tag has
      been purified from Triton X-100-solubilized plasma membranes by nickel metal
      affinity chromatography. Mass spectral analysis of the purified protein is
      consistent with processing of BsSco by signal peptidase II removing an N-terminal
      putative transmembrane sequence to leave an acyl-glyceryl moiety at cysteine
      residue 19. Antibodies, raised against purified, recombinant BsSco, were used to
      characterize the timing of the level of native BsSco in batch cultures of wild
      type B. subtilis. There is a marked lag in the level of native BsSco, but it does
      appear prior to cytochrome c oxidase, which is expressed in late stage growth.
      This work supports a role for BsSco in the assembly of the Cu(A) site of
      cytochrome c oxidase and its functional relationship to the Sco proteins found in
      eukaryotic cells.

PMID- 14680963
TI  - High-level expression of recombinant rabbit cytochrome P450 2E1 in Escherichia
      coli C41 and its purification.
AB  - Cytochrome P450 2E1 (CYP2E1) is of great interest because of its important role
      in the oxidation of numerous drugs and carcinogens. The yields of CYP2E1 obtained
      by the traditional recombinant expression systems have been relatively poor. We
      report here the development of a system for high-level expression of rabbit
      CYP2E1 in Escherichia coli strain C41 (DE3). Expression of the membrane-bound
      CYP2E1 by the pLW01-P450 expression plasmid, which utilizes a T7 promoter, is
      markedly improved by employing E. coli strain C41 (DE3). The pLW01/2E1 expression
      plasmid was successfully constructed and high-level expression of CYP2E1 was
      achieved, which ranged between 900 and 1400 nmol (liter culture)(-1). This yield
      was 9-14-fold higher than other reports of CYP2E1 expression in other E. coli
      strains. This system provides a highly efficient tool for expressing CYP2E1. An
      improved purification procedure for the expressed CYP2E1 involving chromatography
      on diethylaminoethyl cellulose (DE52), Reactive Red-agarose (type 1000-CL), and
      hydroxyapatite is also reported. This procedure allowed recovery of 45% of the
      expressed protein and CYP2E1 with a specific content of 14 nmol/mg protein, which
      showed a single band on a polyacrylamide gel stained with Coomassie brilliant
      blue.

PMID- 14680964
TI  - Expression, purification, and structural study of the EC4 domain of E-cadherin.
AB  - The objective of this work was to produce unlabeled and 15N-labeled EC4 domain
      protein from E-cadherin for studying its structure and binding properties to
      other EC domains as well as to E-cadherin peptides. The EC4 domain of E-cadherin
      was expressed in Escherichia coli from the vector pASK-IBA6 and localized in the
      periplasmic space of E. coli. This protein contains a Streptag sequence at the N
      terminus, and thus was purified using a Strep-Tactin affinity column. However, at
      high concentrations the 15N-labeled EC4 protein showed an unstable conformation.
      Conditions for stabilizing the conformation of this protein were evaluated using
      CD spectroscopy. The CD results showed that this protein has high conformational
      stability in Tris buffer at pH 6.0 in the presence of 10 mM calcium chloride.

PMID- 14680965
TI  - High-level expression and one-step purification of recombinant dengue virus type
      2 envelope domain III protein in Escherichia coli.
AB  - Dengue virus infection poses a serious global public health threat for which
      there is currently no therapy or a licensed vaccine. The domain III of the dengue
      virus encoded envelope protein, which carries multiple conformation-dependent
      neutralizing epitopes, is critical for virus infectivity. We have expressed and
      purified recombinant domain III of dengue virus type-2 envelope, without the aid
      of a carrier protein in Escherichia coli. A 6x His tag was inserted at the N
      terminus to facilitate its one-step purification. The protein was overexpressed
      in the form of insoluble inclusion bodies, which were solubilized under highly
      denaturing conditions and then subjected to a previously optimized arginine
      mediated renaturation protocol. We purified recombinant domain III protein to
      near homogeneity by Ni-NTA affinity chromatography and obtained yields of
      approximately 30 mg/L. The purified protein was recognized in Western analyses by
      monoclonal antibodies specific for the 6x His tag as well as the 3H5 neutralizing
      epitope known to reside in domain III. The authenticity of the recombinant
      protein was also verified in a sandwich ELISA designed to specifically and
      simultaneously identify the 6x His tag and the 3H5 epitope. In addition, murine
      and human polyclonal sera also recognized the recombinant protein. The in vitro
      refolded recombinant protein preparation was biologically functional. It could
      effectively protect cells in culture against dengue virus type-2 infection,
      apparently by blocking the virus from binding to host cells. This
      expression/purification strategy has the potential for inexpensive scale-up and
      may prove to be useful for dengue diagnostics and vaccine development efforts.

PMID- 14680966
TI  - Recombinant replication-restricted VSV as an expression vector for murine
      cytokines.
AB  - Vesicular stomatitis virus (VSV) is a prototypic non-segmented, negative-strand
      RNA virus that rapidly and efficiently shuts down the production of host cell
      encoded proteins and utilizes the cell's protein production machinery to express
      high levels of virally encoded proteins. In an effort to take advantage of this
      characteristic of VSV, we have employed a reverse genetics system to create
      recombinant forms of VSV encoding a variety of murine cytokines. Previous studies
      have revealed that cells infected with recombinant VSV that lack expression of
      the surface glycoprotein (G protein), designated deltaG-VSV, more efficiently
      express and secrete recombinant proteins than do recombinant "wild-type" VSV.
      Therefore, murine cytokine-expressing recombinants were produced as deltaG
      viruses. Propagation of these deltaG viruses in cells that transiently express G
      protein in vitro results in G-complemented virions that can infect cells, shut
      down host protein synthesis, and express at high levels each virally encoded
      protein (including the designated cytokine). We assessed the ability of each
      deltaG-VSV construct to express recombinant cytokine by infecting BHK cells and
      then monitoring/measuring the production of the desired cytokine. When possible,
      the bioactivity of the cytokine products was also measured. The results presented
      here reveal that large quantities of bioactive cytokines can be produced rapidly
      and inexpensively using deltaG-VSV as a protein expression system.

PMID- 14680967
TI  - Affinity precipitation of Aspergillus niger pectinase by microwave-treated
      alginate.
AB  - Affinity precipitation is a simple, single plate separation process in which the
      complex of a smart macroaffinity ligand with the target protein (from a crude
      broth) can be selectively precipitated by application of a suitable stimulus.
      Alginate is a copolymer of guluronic acid and mannuronic acid residues and
      precipitates with Ca(2+) ions. It was found to bind to pectinase present in a
      commercial preparation of Aspergillus niger, Pectinex Ultra-SPL. Microwave
      pretreatment of alginate at 75 degrees C was found to enhance the selectivity of
      the affinity precipitation. Using microwave-treated alginate, 83% of the enzyme
      activity with 20-fold purification could be recovered. SDS-PAGE upon silver
      staining confirmed the enhanced selectivity of affinity precipitation when
      microwave-treated alginate was used.

PMID- 14680968
TI  - Recombinant cold-adapted trypsin I from Atlantic cod-expression, purification,
      and identification.
AB  - Atlantic cod trypsin I is a cold-adapted proteolytic enzyme exhibiting
      approximately 20 times higher catalytic efficiency (kcat/KM) than its mesophilic
      bovine counterpart for the simple amide substrate BAPNA. In general, cold-adapted
      proteolytic enzymes are sensitive to autolytic degradation, thermal inactivation
      as well as molecular aggregation, even at temperatures as low as 18-25 degrees C
      which may explain the problems observed with their expression, activation, and
      purification. Prior to the data presented here, there have been no reports in the
      literature on the expression of psychrophilic or cold-adapted proteolytic enzymes
      from fish. Nevertheless, numerous cold-adapted proteolytic microbial enzymes have
      been successfully expressed in bacteria and yeast. This report describes
      successful expression, activation, and purification of the recombinant cod
      trypsin I in the His-Patch ThioFusion Escherichia coli expression system. The E.
      coli pThioHis expression vector used in the study enabled the formation of a
      fusion protein between a highly soluble fraction of HP-thioredoxin contained in
      the vector and the N-terminal end of the precursor form of cod trypsin I. The HP
      thioredoxin part of the fusion protein binds to a metal-chelating ProBond column,
      which facilitated its purification. The cod trypsin I part of the purified fusion
      protein was released by proteolytic cleavage, resulting in concomitant activation
      of the recombinant enzyme. The recombinant cod trypsin I was purified to
      homogeneity on a trypsin-specific benzamidine affinity column. The identity of
      the recombinant enzyme was demonstrated by electrophoresis and chromatography.

PMID- 14680969
TI  - Expression and purification of the recombinant diphtheria fusion toxin DT388IL3
      for phase I clinical trials.
AB  - A genetically engineered fusion toxin targeted to acute myeloid leukemia (AML)
      blasts was designed with the first 388 amino acid residues of diphtheria toxin
      with an H-M linker fused to human interleukin-3. The cDNA was subcloned in the
      pRK bacterial expression plasmid and used to transform BLR (DE3) Escherichia
      coli. A single transformed colony was grown in Superbroth with ampicillin;
      bacteria were centrifuged at an OD(650) of 1.3; master cell bank aliquots of
      bacteria in 30% glycerol/Superbroth were frozen and stored at -80 degrees C.
      Master cell bank bacteria were diluted 1500-fold into Superbroth and recombinant
      protein was induced with 1 mM IPTG at an OD(650) of 0.6. After two additional
      hours of fermentation, inclusion bodies were isolated, washed, and denatured in
      guanidine hydrochloride and dithioerythritol. Recombinant protein was refolded by
      diluted 100-fold in cold buffer with arginine and oxidized glutathione. After
      dialysis, purified protein was obtained after anion-exchange, size exclusion on
      FPLC, and polymyxin B affinity chromatography. The final material was filter
      sterilized, aseptically vialed, and stored at -80 degrees C. Seventy-five 3-L
      bacterial culture preparations were made and pooled for the AT-1 batch (568 mL)
      and twenty-four 3-L bacterial culture preparations were made and pooled for the
      AT-2 batch (169 mL). The final product was characterized by Coomassie Plus
      protein assay, Coomassie-stained SDS-PAGE, limulus amebocyte lysate endotoxin
      assay, human AML TF/H-ras cell cytotoxicity assay, sterility, tandem mass
      spectroscopy, IL3 receptor binding affinity, ADP ribosylation activity,
      inhibition of normal human CFU-GM, disulfide bond analysis, immunoblots, peptide
      mapping, stability, HPLC TSK3000, N-terminal sequencing, E. coli DNA
      contamination, C57BL/6 mouse toxicity, cynomolgus monkey toxicity, and
      immunohistochemistry. Yields were 25.7+/-5.6 mg/L bacterial culture of denatured
      fusion toxin. After refolding and chromatography, final yields were 20+/-11% or 5
      mg/L. Vialed product was sterile. Batches were in 0.25 M sodium chloride/5 mM
      Tris, pH 8, and had protein concentrations of 1.8-1.9 mg/mL. Purity by SDS-PAGE
      was 99+/-1%. Aggregates by HPLC were <1 %. Potency revealed a 48 h IC(50) of 6-8
      pM on TF/H-ras cells. Endotoxin levels were 1 eu/mg. The remaining chemical and
      biologic assays confirmed the purity, composition, and functional activities of
      the molecule. The LD(10) in mice was 250 microg/kg/day every other day for six
      doses. The MTD in monkeys was 60 microg/kg/day every other day for six doses.
      Drug did not react with tested frozen human tissue sections by
      immunohistochemistry. There was no evidence of loss of solubility, proteolysis
      aggregation, or loss of potency over 6 months at -80 and -20 degrees C. Further,
      the drug was stable at 4 and 25 degrees C in the plastic syringe and
      administration tubing for 24 h and at 37 degrees C in human serum for 24 h. The
      synthesis of this protein drug should be useful for production for clinical phase
      I/II clinical trials and may be suitable for other diphtheria fusion toxins
      indicated for clinical development.

PMID- 14680970
TI  - Purification and characterization of the DNA binding domain of Saccharomyces
      cerevisiae meiosis-specific transcription factor Ndt80.
AB  - Ndt80 is a Saccharomyces cerevisiae meiosis-specific transcription factor
      responsible for promoting the stage-specific expression of a family of genes
      referred to as middle sporulation genes. Many members of this gene family are
      essential for the completion of meiotic chromosome segregation. Thus, Ndt80 is
      essential for the completion of meiosis. Ndt80 is highly regulated both
      transcriptionally and post-translationally. To facilitate biochemical analysis of
      Ndt80, we have expressed the DNA binding domain in Escherichia coli and purified
      the recombinant protein with an affinity chromatography procedure. In addition we
      have dissected the amino-terminus of Ndt80 to delimit the functional DNA binding
      domain. This analysis shows that the amino-terminal 40 amino-acids of Ndt80,
      although not essential for its DNA binding activity, do have an effect on its
      ability to bind specifically to its target DNA sequence. In addition, we show
      that the Ndt80 DNA binding domain can be phosphorylated by the meiosis-specific
      protein kinase Ime2 in vitro, but contrary to our initial hypothesis this
      phosphorylation does not significantly affect the affinity of Ndt80 for its
      target DNA sequence.

PMID- 14680971
TI  - Recombinant expression and characterization of an extremely hyperthermophilic
      archaeal histone from Pyrococcus horikoshii OT3.
AB  - A histone-like gene, PHS051 from hyperthermophilic archaeon Pyrococcus horikoshii
      OT3 strain, was cloned, sequenced, and expressed in Escherichia coli. The
      recombinant histone, HPhA, encodes a protein of 70 amino acids with a molecular
      weight of 7868Da. Amino acid sequence analysis of HPhA showed high homology with
      other archaeal histones and eukaryal core histones. The HPhA was purified to
      homogeneity by heat precipitation and affinity chromatography. Gel
      electrophoresis mobility shift assays demonstrate that the purified HPhA has high
      affinity to DNA. The complex of the HPhA and DNA allows DNA to be protected from
      cleavage by the restriction enzyme TaqI at 65 degrees C. Circular dichroism
      spectra reveal that the conformation of the recombinant histone HPhA becomes
      looser when temperatures increase from 25 to 90 degrees C. The HPhA has inherited
      a remarkable thermostability especially in the presence of 1M KCl and retained
      DNA binding activity at extreme temperature, which is consistent with our
      previous report about its structure stability analyzed by X-ray crystallography.

PMID- 14680973
TI  - Galactitol and galactonate in red blood cells of galactosemic patients.
AB  - The red blood cell (RBC) concentration of galactitol and galactonate was measured
      in 27 patients with galactose-1-phosphate uridyltransferase (GALT) deficiency
      galactosemia and 19 non-galactosemic subjects by a newly devised isotope dilution
      gas chromatography/mass spectrometry (GC/MS) method. The method utilizing
      UL[13C]galactitol and UL[13C]galactonate was reproducible with excellent
      precision and recovery of 99%. The RBC galactitol in galactosemic patients on
      galactose-restricted diets averaged 5.98+/-1.2 microM (M+/-SD) with a range of
      3.54-8.81 microM. The mean in non-galactosemic patients was 0.73+/-0.31 microM
      with a range of 0.29-1.29 microM. The mean of RBC galactonate in the same
      galactosemic patients was 4.16+/-1.32 microM (M+/-SD) with a range of 0.68-6.47,
      while the mean in non-galactosemic subjects was 1.94+/-0.96 (M+/-SD) with a range
      of 0.69-3.84. In galactosemic RBC the galactitol was higher than galactonate
      while this was reversed in non-galactosemic cells. RBC galactose-1-phosphate (Gal
      1-P) measured at the same time as galactitol and galactonate was 30 times the
      level of the other two metabolites. There was no relationship between RBC Gal-1-P
      and galactitol or galactonate. The ability to measure all three galactose
      metabolites in the same procedure offers the possibility of augmented monitoring
      of the galactose metabolic status of patients. The measurement of RBC galactitol
      and galactonate presents a new means of characterizing galactosemic patients and
      their levels monitored over time may provide new insight in the development of
      long-term complications observed in afflicted patients.

PMID- 14680972
TI  - Expressing an antibacterial protein in bacteria for raising antibodies.
AB  - Magainins are small peptides with broad-spectrum activity against a range of
      plant and animal microbial pathogens. To detect magainin peptides in applications
      such as Western blot analysis and enzyme-linked immunosorbent assays, specific
      antibodies that recognize magainin peptides are required. The production of
      antibodies against small peptides injected into host animals poses problems with
      respect to eliciting an adequate immunogenic response due to the small size of
      the molecules. To increase the immunogenicity of a target peptide, it may be
      expressed as part of a larger fusion protein. However, expression of an
      antimicrobial peptide in bacteria may be cytotoxic to the host or subjected to
      degradation by host-derived peptidases. To overcome these potential problems, we
      fused the DNA coding sequence of a magainin gene analogue within the sequence of
      a bacterial thioredoxin gene. The subsequent gene fusion comprising a bacterial
      thioredoxin gene with a magainin coding sequence ligated at the active site of
      thioredoxin was successfully translated in a bacterial expression system. The
      fusion protein was non-toxic to the host bacteria. This represents a novel
      strategy to express antimicrobial peptides in a bacterial expression system. The
      fusion protein, purified by molecular size separation, was recovered in a soluble
      form following electroelution from polyacrylamide gels. Sufficient fusion protein
      was obtained for injection into rabbits and antibodies were obtained from rabbit
      sera that selectively recognized magainin peptides in Western blot analysis.

PMID- 14680974
TI  - Cholesterol biosynthesis is not defective in peroxisome biogenesis defective
      fibroblasts.
AB  - To evaluate the presumed peroxisomal involvement in cholesterol/isoprenoid
      biosynthesis, we determined the protein levels and activities of five different
      enzymes of the presqualene segment of the cholesterol/isoprenoid biosynthetic
      pathway in primary skin fibroblasts of selected patients with a peroxisomal
      biogenesis disorder (PBD). These five enzymes all have been reported to be partly
      or exclusively peroxisomal and include HMG-CoA reductase, mevalonate kinase,
      phosphomevalonate kinase, mevalonate pyrophosphate decarboxylase, and isopentenyl
      pyrophosphate isomerase. To exclude that genetic differences, resulting in
      different defects in peroxisomal biogenesis, have differential effects on the
      activity of the cholesterol biosynthetic enzymes and on de novo cholesterol
      biosynthesis, we chose fibroblasts of patients with defined defects in one of
      four different PEX genes leading to Zellweger syndrome (PEX1, PEX5, PEX16 or
      PEX19). We found that all enzymes measured are at least as active in the
      peroxisome-deficient cells cultured in cholesterol-depleted medium as in
      identically cultured control cells. This indicates that if these presumed
      peroxisomal proteins are mislocalized to the cytosol they do not loose their
      activity, nor get degraded unlike most other authentic peroxisomal proteins. We
      also measured de novo cholesterol synthesis from radio-labeled acetate in all
      cell lines and found similar or even elevated rates for the PBD cells when
      compared to controls. Our results imply that functional peroxisomes are not a
      prerequisite for the functioning of enzymes involved in cholesterol/isoprenoid
      biosynthesis and as such raise doubts about the true involvement of peroxisomes
      therein.

PMID- 14680975
TI  - Variants in the PPARgamma gene affect fatty acid and glycerol metabolism in
      familial combined hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCHL) is a common genetic lipid disorder
      characterized by premature coronary artery disease, dyslipidemia, insulin
      resistance, and impaired adipose tissue free fatty acid (FFA) metabolism.
      Increased adipose tissue FFA flux towards the liver may, in part, contribute to
      reduced insulin sensitivity and hyperlipidemia in FCHL. It was the objective of
      the present study to evaluate the contribution of the peroxisome proliferator
      activated receptor gamma (PPARgamma) gene to FCHL traits related to adipocyte
      lipid metabolism, dyslipidemia, and insulin resistance. In a case-control panel
      consisting of 79 FCHL probands and 124 spouse controls, polymorphic marker
      D3S1259 and three intragenic PPARgamma variants, i.e., 161C > T, Pro12Ala, and
      Pro115Gln, were studied. The Pro115Gln variant was not found in any of the
      subjects. Allele frequencies of the 161C > T, Pro12Ala variants, and D3S1259 did
      not differ significantly between FCHL probands and spouses. In FCHL probands,
      individuals heterozygous or homozygous for the 161T allele had lower plasma
      concentrations of FFA (P < 0.05) and glycerol (P < 0.01). No significant
      associations were found in spouses. These findings identify PPARgamma as a
      quantitative trait locus for FFA and glycerol, against a background of insulin
      resistance for adipose tissue lipid metabolism, and therefore as a modifier gene
      in FCHL.

PMID- 14680976
TI  - Mild citrullinemia in Caucasians is an allelic variant of argininosuccinate
      synthetase deficiency (citrullinemia type 1).
AB  - Citrullinemia is caused by either deficiency of argininosuccinate synthetase
      (ASS, citrullinemia type 1) or a defect of the SLC25A13 gene encoding a
      mitochondrial aspartate-glutamate transporter (citrullinemia type II).
      Citrullinemia type 1-referred to as classical citrullinemia-is characterized by
      largely elevated concentrations of citrulline, manifesting with acute
      hyperammonemic crises predominantly early in life and occurs panethnically.
      Citrullinemia type II is a rare multisystem-disorder nearly exclusively observed
      in the Japanese population and characterized by less pronounced elevations of
      plasma citrulline and mainly a late onset of clinical symptoms. Here, we
      investigated 21 citrullinemic patients (mean peak plasma citrulline 1023
      micromol/l, range 152-3360), all of whom remained asymptomatic during the
      observation period (6-156 months). These patients were referred to as mild
      citrullinemia due to less striking peak citrulline concentrations or absent
      clinical symptoms. Extended newborn screening using tandem mass spectrometry
      detected 15/21 patients, 4/21 patients were identified by investigation of
      siblings, 2/21 during metabolic work-up of unspecific neurological symptoms. We
      characterized the genetic defects in all affected families and found all patients
      affected by citrullinemia type 1 due to mutations of the ASS gene. We identified
      15 different mutations, 14/15 missense and 1/15 nonsense, 6/15 were novel
      mutations. This is the first genetic study in a series of patients with hitherto
      asymptomatic citrullinemia. According to the mutations found in this study, mild
      citrullinemia seems to be primarily related to the human ASS gene, at least in
      patients of caucasian origin.

PMID- 14680977
TI  - Fabry disease: D313Y is an alpha-galactosidase A sequence variant that causes
      pseudodeficient activity in plasma.
AB  - Fabry disease, an X-linked recessive lysosomal storage disease, results from the
      deficient activity of the exogalactosidase, alpha-galactosidase A (alpha-Gal A).
      To date, over 270 disease-causing mutations have been identified; however, no
      coding sequence variants have been reported. In the course of enzyme diagnostic
      testing, a normal female control had low plasma and leukocyte alpha-Gal A
      activities. Sequencing her alpha-Gal A gene revealed the D313Y substitution (GAT
      to TAT at cDNA nucleotide 937). alpha-Gal A mutation and enzyme analyses of
      family members revealed X-linked transmission and leukocyte alpha-Gal A enzymatic
      activities in females, consistent with Lyonization. Since D313Y was reported in a
      classically affected male who had the double mutation, D313Y and G411D, efforts
      were undertaken to characterize these lesions. Expression of D313Y, G411D, and
      the doubly mutated construct, D313Y/G411D, resulted in alpha-Gal A levels of 76,
      2.9, and 1.7% of mean expressed wild-type activity, respectively. Biosynthetic
      studies revealed essentially normal processing of the D313Y subunit, but the
      absence of the mature subunit encoded by the G411D and D313Y/G411D constructs.
      Thus, G411D is the disease-causing mutation, while D313Y is the first coding
      sequence variant identified in the human alpha-Gal A gene.

PMID- 14680978
TI  - Functional analysis of MCCA and MCCB mutations causing methylcrotonylglycinuria.
AB  - Methylcrotonylglycinuria (MCG; MIM 210200) is an autosomal recessive inherited
      human disorder caused by the deficiency of 3-methylcrotonyl-CoA carboxylase (MCC,
      E.C.6.4.1.4), involved in leucine catabolism. This mitochondrial enzyme is one of
      the four biotin-dependent carboxylases known in humans. MCC is composed of two
      different types of subunits, alpha and beta, encoded by the nuclear genes MCCA
      and MCCB, respectively, recently cloned and characterized. Several mutations have
      been identified, in both genes, the majority are missense mutations along with
      splicing mutations and small insertions/deletions. We have expressed four
      missense mutations, two MCCA and two MCCB mapping to highly evolutionarily
      conserved residues, by transient transfection of SV40-transformed deficient
      fibroblasts in order to confirm their pathogenic effect. All the missense
      mutations expressed resulted in null or severely diminished MCC activity
      providing direct evidence that they are disease-causing ones. The MCCA mutations
      have been analysed in the context of three-dimensional structural information
      modelling the changes in the crystallized biotin carboxylase subunit of the
      Escherichia coli acetyl-CoA carboxylase. The apparent severity of all the MCC
      mutations contrasts with the variety of the clinical phenotypes suggesting that
      there are other cellular and metabolic unknown factors that affect the resulting
      phenotype.

PMID- 14680979
TI  - Increased expression of manganese-superoxide dismutase in fibroblasts of patients
      with CPEO syndrome.
AB  - Alterations in the expression of free radical scavenging enzymes and production
      of reactive oxygen species (ROS) in tissue cells may contribute to the
      pathogenesis of mitochondrial diseases such as chronic progressive external
      ophthalmoplegia (CPEO) syndrome. Since the mitochondria with impaired respiratory
      function in affected tissues generate more ROS via electron leakage, we examined
      the expression levels of free radical scavenging enzymes in primary culture of
      muscle fibroblasts of eight patients with CPEO syndrome. The results showed that
      the enzyme activity and protein levels of Mn-SOD of the fibroblasts from CPEO
      patients were significantly increased but those of Cu,Zn-SOD, catalase and
      glutathione peroxidase (GPx) were not increased compared with controls. A similar
      pattern was observed in the mRNA levels of Mn-SOD and GPx in muscle fibroblasts
      of all CPEO patients. The activity ratios of Mn-SOD/catalase and Mn-SOD/GPx in
      muscle fibroblasts of the CPEO patients were increased 1.7-3.4 and 1.8- to 5.3
      fold, respectively, compared to those of the controls. Moreover, by using flow
      cytometry we found that the production of O2(*-) and H2O2 in the fibroblasts was
      about 2 times higher than those of controls. The 8-OHdG/dG ratios in total DNA of
      muscle biopsies from three CPEO patients were much higher than those of age
      matched controls as determined by high performance liquid chromatography (HPLC).
      In the light of these findings, we suggest that the increase in expression of Mn
      SOD, ROS production and oxidative damage in affected tissues may play an
      important role in the pathogenesis and progression of the CPEO syndrome.

PMID- 14680980
TI  - Plasma total homocysteine concentrations in adults with growth hormone (GH)
      deficiency: effects of GH replacement.
AB  - Growth hormone (GH) deficiency is associated with increased cardiovascular
      morbidity and mortality. GH treatment improves the profile of many cardiovascular
      risk markers in individuals with GH deficiency (GHD). The aim of the present was
      to assess whether GH replacement may decrease plasma total homocysteine, an
      independent cardiovascular risk factor, thus potentially contributing to benefits
      of GH replacement in adult subjects with GHD. Twenty-five patients (17 female, 8
      male), mean age 39-years, with GHD were studied. GH status had been determined by
      an insulin tolerance test and/or arginine stimulation test. After an overnight
      fast, plasma insulin, IGF-1, total homocysteine (Hcy), free thyroxine (FT4),
      creatinine, vitamin B12, and folate were measured at baseline (V1), 3 months (V2)
      and then at 6 months (V3) on GH treatment. The data were analysed by hierarchical
      statistical models, univariate and multivariate correlation. GH treatment
      resulted in an increase in IGF-1 (p<0.001, p<0.001), and insulin (p=0.068,
      p<0.001), at each visit, respectively. Hcy levels increased from V1 to V2 (7.7+/
      0.53 to 9.15+/-0.45 micromol/L; p=0.051), but this was followed by a decline at
      V3 (to 8.8+/-0.59), so that the overall change of Hcy levels from V1 to V3, once
      individuals had achieved 'adequate' GH replacement, was no longer significantly
      different (p=0.090). When separated by gender, at 6 months (V3) there was a
      small, but significant increase in Hcy in men (p=0.028), but not in women
      (p=0.58). There was no significant change in B12, folate, free T4 or creatinine
      levels. Univariate analysis revealed that only B12 and folate showed significant
      negative relationships with Hcy (B12: parameter= -0.013, p<0.001; folate:
      parameter=-1.31, p<0.001), but not between Hcy and IGF-1 (p=0.18). In a multiple
      variable model, both B12 and folate remained significantly negatively associated
      with plasma total homocysteine (p=0.018; p<0.001, respectively). In this
      observational study normalisation of IGF-1 levels in adult subjects with growth
      hormone deficiency was not associated with a fall in total homocysteine. Before
      firm conclusions can be drawn about the contribution of changes in plasma
      homocysteine concentrations to cardiovascular prognosis in adult GHD patients
      receiving GH replacement, further controlled studies are required.

PMID- 14680981
TI  - Variants in the interleukin 6 receptor gene are associated with obesity in Pima
      Indians.
AB  - Circulating levels of the cytokine interleukin 6 (IL-6) are elevated in obesity,
      correlate with body mass index (BMI), and predict the development of type 2
      diabetes mellitus (T2DM). A promoter polymorphism in the IL6 gene is associated
      with obesity, altered levels of insulin sensitivity, and T2DM. IL-6 exerts its
      effects by binding to the IL-6 receptor (IL-6R) and levels of IL-6R have been
      correlated with BMI. It is possible that IL6R variants may also be related to
      obesity, but to our knowledge, no study has yet examined this relationship. The
      objective of this study was to examine the relationship between genetic variants
      in the IL6R gene and obesity in Pima Indians, a population prone to excess
      adiposity. We sequenced 6kb of the IL6R gene, corresponding to all exons, exon
      intron boundaries, and 2kb of promoter in 30 Pima Indians. We identified six
      single nucleotide polymorphisms (SNPs) in the IL6R gene: a predicted Asp --> Ala
      substitution at position 358, a variant in the 3'-untranslated region, and 4
      intronic SNPs. All SNPs were in strong linkage disequilibrium (D' >/= 0.90) and
      varied in minor allele frequency from 0.33 to 0.48. Association between IL6R
      genotype and BMI (kg/m(2)) was assessed in approximately 700 nondiabetic, full
      heritage Pima Indians. For each SNP, individuals carrying the variant allele had
      a higher mean BMI compared to those with the wild-type allele (range: [37.3+/-7.2
      38.2+/-7.0] vs. [35.5+/-7.3-36.0+/-7.5]; P=0.02-0.004). Our findings suggest that
      genetic variants in the IL6R gene may play a role in susceptibility to obesity.
      Assessment of these SNPs in other populations will be useful to determine the
      magnitude of obesity risk.

PMID- 14680982
TI  - Association of polymorphisms of the osteoprotegerin gene with bone mineral
      density in Japanese women but not men.
AB  - Given that osteoprotegerin plays an important role in bone remodeling, the
      osteoprotegerin gene may be a candidate locus for susceptibility to osteoporosis.
      The relation of polymorphisms in the promoter of the osteoprotegerin gene to bone
      mineral density (BMD) was examined in a Japanese population-based prospective
      cohort study with randomly recruited subjects (1095 women and 1125 men for the
      950T --> C polymorphism, 1094 women and 1127 men for the 245T --> G
      polymorphism). BMD at the radius was measured by peripheral quantitative computed
      tomography, and that for the total body, lumbar spine, right femoral neck, right
      trochanter, and right Ward's triangle was measured by dual-energy X-ray
      absorptiometry. Genotypes were determined with a fluorescence-based allele
      specific DNA primer assay system. Among 950T --> C genotypes, BMD for the
      proximal radius was lower in premenopausal women with the CC genotype than in
      those with the TT or TC genotype; the difference in BMD between the two groups
      was 3.9% (P=0.0075). Among 245T --> G genotypes, BMD for the radius, total body,
      femoral neck, trochanter, and Ward's triangle was lower in postmenopausal women
      with the GG genotype than in those with the TT or TG genotype, the TT genotype,
      or the TG genotype; the differences in BMD between the GG genotype and the TT or
      TG genotype were 19.8% for the distal radius (P=0.0015), 13.1% for the proximal
      radius (P=0.0095), 11.2% for the total body (P=0.0013), 12.9% for the femoral
      neck (P=0.0067), 18.7% for the trochanter (P=0.0008), and 27.1% for Ward's
      triangle (P=0.0038). BMD was not associated with the 950T --> C or 245T --> G
      genotypes in men. The present results implicate the osteoprotegerin gene as a
      susceptibility locus for reduced BMD in Japanese women.

PMID- 14680983
TI  - Prognostic value of regional cerebral metabolism in patients undergoing dementia
      evaluation: comparison to a quantifying parameter of subsequent cognitive
      performance and to prognostic assessment without PET.
AB  - It is difficult to accurately forecast the clinical course of many patients
      presenting with mild cognitive problems. The utility in prognostic evaluation of
      various parameters of brain structure and function that can now be noninvasively
      measured remains to be clearly defined. The present work examined the value of
      regional cerebral metabolism, assessed with positron emission tomography (PET)
      and [(18)F]fluoro-2-deoxyglucose, in this context. PET scans of 167 patients
      (mean Mini-Mental State Examination (MMSE)=24 of 30 possible points) were
      classified as being positive or negative for evidence of progressive dementia.
      Results of scans were compared to patients' subsequent clinical course in general
      and in particular, to their changes in MMSE scores, for up to 10 years following
      PET. Data were further stratified according to the predictions of referring
      physicians based upon clinical assessments that had been performed up until the
      time of PET. Among those patients for whom a progressive dementing course had
      been predicted by PET criteria (but not those who were predicted by PET criteria
      to remain stable) a significant decline in general cognitive performance and MMSE
      scores occurred in the period following PET. Among those patients predicted by
      clinical criteria to have a progressive dementing illness, 94% of those with
      positive PET scans did suffer a progressive decline, while only 25% of those with
      negative scans progressed (relative risk 3.8). Similarly, among those patients
      who had been predicted by clinical criteria to remain cognitively stable, 74% of
      those with positive PET scans nevertheless suffered progressive decline, compared
      with 4% of those with negative PET scans (relative risk 18.4). These data
      indicate that evaluation of brain metabolism by PET in appropriately selected
      patients may improve the accuracy of clinical prognostic assessment.

PMID- 14680984
TI  - Screening of nine SLC25A13 mutations: their frequency in patients with citrin
      deficiency and high carrier rates in Asian populations.
AB  - Deficiency of citrin encoded by SLC25A13 causes adult-onset type II citrullinemia
      (CTLN2) and idiopathic neonatal hepatitis (NICCD). So far we have diagnosed 126
      (3) CTLN2 and 103 (4) NICCD patients in Japan (and other countries). From
      preliminary population analysis of the known nine SLC25A13 mutations, we found
      that the carrier frequency is high in China (1/79), Taiwan (1/98), and Korea
      (1/50) as well as Japan (1/69), suggesting that many patients with citrin
      deficiency exist in East Asia.

PMID- 14680986
TI  - 776C>G polymorphism of the transcobalamin II gene as a risk factor for spina
      bifida.

PMID- 14680985
TI  - Novel mutations in arylsulfatase A gene in three Ukrainian families with
      metachromatic leukodystrophy.
AB  - Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by the
      deficiency of arylsulfatase A (ARSA) or saposin B. The majority of mutations
      identified in patients with MLD are unique within individual families. Here, we
      report on the novel missense mutations (F247S, D381E, and A469G) and the known
      mutations "A" allele and P136S in the ARSA gene in three unrelated Ukrainian
      families with MLD. The mutations F247S and P136S were found in compound
      heterozygous with the "A" allele in two patients with juvenile onset MLD. The
      clinical features of the typical patient with genotype D381E/A469G (early onset
      with very rapid manifestation of disease) suggest the reason to distinguish an
      early infantile MLD variant.

PMID- 14680988
TI  - A functional observational battery for use in canine toxicity studies:
      development and validation.
AB  - The most commonly used nonrodent species in regulatory toxicity and safety
      assessment studies has been and remains the dog, with the beagle being the
      standard breed employed. Although a standard functional observational battery
      (FOB) or neurobehavioral screen for use in rodents (primarily rats) has been
      incorporated into rodent studies since the late 1980s, this is not the case in
      nonrodents. In the pharmaceutical area (where repeat exposure nonrodent studies
      are generally required to develop a drug for humans), some work has been
      previously conducted towards developing a similar screen in the dog but progress
      has been limited. Given both the differential metabolism and sensitivity of the
      dog compared to rodents and the extreme desirability of having as complete a set
      of toxicity and/or functionality measures in the same species (to simplify and
      improve the accuracy of dose/response metrics) as possible, the need for such a
      standardized and validated methodology is clear. Study data from prior work
      establish the susceptibility of dogs to a wide variety of neurotoxic agents,
      including 6-aminonicotinamide (ANA), methanol, lasalocid, metronidazole,
      acrylamide, clinoquinol, organo tins, and mercury. Additionally, the dog is
      likewise well established as a sensitive model for a wide range of peripheral and
      central nervous system-active pharmacologic agents, as required by recent
      regulatory requirements for safety pharmacology evaluations. Here we report on a
      robust and yet sensitive noninvasive screening methodology for detecting and
      providing initial quantitation and characterization of such direct and indirect
      neurotoxic and neuropharmacologic effects that has been developed. Additionally,
      an analysis and interpretation component that allows differentiation of
      neurotoxic from neuropharmacologic activities has also been adapted from prior
      work by one of the authors. Comparative species difference in sensitivity to
      neuroactive agents are also discussed, as well as means for integrating this
      evaluation screen into existing standard design. Particularly, with the recent
      promulgation of safety pharmacology testing requirements (the in vivo
      cardiovascular component of which is performed in the dog), the availability of
      such an evaluation paradigm presents a valuable potential addition to existing
      study designs without increasing animal usage.

PMID- 14680989
TI  - Oxidative stress in rats after 60 days of hypergalactosemia or hyperglycemia.
AB  - Two of the models used in current diabetes research include the hypergalactosemic
      rat and the hyperglucosemic, streptozotocin-induced diabetic rat. Few studies,
      however, have examined the concurrence of these two models regarding the effects
      of elevated hexoses on biomarkers of oxidative stress. This study compared the
      activities of superoxide dismutase, catalase, glutathione peroxidase, and
      glutathione reductase and the concentrations of glutathione, glutathione
      disulfide, and thiobarbituric acid reactants (as a measure of lipid peroxidation)
      in liver, kidney, and heart of Sprague-Dawley rats after 60 days of either a 50%
      galactose diet or insulin deficiency caused by streptozotocin injection. Most
      rats from both models developed bilateral cataracts. Blood glucose and
      glycosylated hemoglobin A(1c) concentrations were elevated in streptozotocin
      diabetic rats. Streptozotocin diabetic rats exhibited elevated activities of
      renal superoxide dismutase, cardiac catalase, and renal and cardiac glutathione
      peroxidase, as well as elevated hepatic lipid peroxidation. Insulin treatment of
      streptozotocin-induced diabetic rats normalized altered markers. In galactosemic
      rats, hepatic lipid peroxidation was increased whereas glutathione reductase
      activity was diminished. Glutathione levels in liver were decreased in diabetic
      rats but elevated in the galactosemic rats, whereas hepatic glutathione disulfide
      concentrations were decreased much more in diabetes than in galactosemia. Insulin
      treatment reversed/prevented all changes caused by streptozotocin-induced
      diabetes. Lack of concomitance in these data indicate that the 60-day galactose
      fed rat is not experiencing the same oxidative stress as the streptozotocin
      diabetic rat, and that investigators must be cautious drawing conclusions
      regarding the concurrence of the effects of the two animal models on oxidative
      stress biomarkers.

PMID- 14680990
TI  - In vitro inhibition of blood cholinesterase activities from horse, cow, and rat
      by tetrachlorvinphos.
AB  - The organophosphorus insecticide tetrachlorvinphos (TCVP) is commonly used as a
      feed-through larvicide in many livestock species, including cattle and horses.
      Cholinesterase (ChE) activity in blood (generally plasma or whole blood) is often
      employed to assess organophosphorus insecticide intoxication in animals as well
      as humans. In many species, including horse and man, plasma contains
      predominantly butyrylcholinesterase whereas red blood cells in all species
      express exclusively acetylcholinesterase. To evalulate the comparative
      interaction of TCVP with blood ChEs in different species, we compared the in
      vitro sensitivity of ChE activity in plasma and erythrocytes from horse, cow, and
      rat. Horse plasma ChE was most sensitive (IC(50), 30 minutes, 30 degrees C = 97
      nM), whereas horse erythrocyte ChE activity was least sensitive (IC(50) > 1 mM).
      In contrast, cow plasma ChE showed lower sensitivity (IC(50) = 784 microM) to
      inhibition by TCVP than erythrocyte ChE (IC(50) = 216 microM). Rat plasma and
      erythrocyte ChE activities had relatively similar sensitivity to TCVP (IC(50) =
      54 microM and 78 microM, respectively). The results suggest that plasma and
      erythrocyte ChE from horse, cow, and rat show marked species- and blood fraction
      dependent differences in sensitivity to TCVP. Knowledge of such differences in
      sensitivity of blood ChE activities to TCVP may be important in the clinical
      interpretation of intoxication with this pesticide across species.

PMID- 14680991
TI  - Food safety: risk assessment methodology and decision-making criteria.
AB  - As our scientific technology grows, risk assessment methods become more complex
      and, therefore, open to greater scientific debate. Risk assessment has always
      been a part of the regulatory notification and approval process for foods.
      However, the methodologies applied to risk assessment and decision-making have
      become diverse, dependent on a number of features, including the areas of the
      world in which one operates, the need to use cumulative risk assessment for
      pesticides and other ingredients or alternative risk assessment considerations
      for evaluating nontraditional or bioengineered foods. Diverse institutional
      structures within a single federal regulatory authority may tend to lead to
      diversity in risk outcomes that creates policy decisions that complicate and
      confuse the risk management process. On top of this challenge, decisions become
      more complicated by the need to examine beneficial factors of foods rather than
      the adverse effects of foods and food additives. Foods are a complex mixture of
      ingredients. Regulatory groups recognize the need to use new approaches for
      evaluating the safety and risks associated with foods and food additives, and to
      do so in a timely manner. The United States Food and Drug Administration (US FDA)
      in its need to ensure standards of "reasonable certainty of no harm" continues to
      explore alternative means to be responsive to petitioners as well as continue to
      examine scientifically validated means, e.g., quantitative structure-activity
      relationship (QSAR), and computer-assisted programs, within the approval process
      to assist in the evaluation of risks. Another means to improve the risk
      management process would include the cumulative risk assessment of pesticides
      that will, no doubt, be the beginning of more intensive efforts to understand
      cumulative exposures and the inherent risks from multiple pathways of exposure.
      The passage of the Food Quality Protection Act (FQPA) resulted in developing
      additional risk assessment methodologies and approaches to assess the potential
      for multiple exposures and risks. Addressing the international criteria used in
      decision-making related to foods safety assessment has resulted in acceptable
      intake values for food ingredients for carcinogens and noncarcinogens that, in
      general, tend to be more stringent in the United States compared to Europe.
      Clearly, the need for harmonization of risk assessment criteria and the impact of
      the decision process on regulatory approvals and safety assessment is a future
      need for the continued assurances of food safety. The topics presented in this
      paper are based on a symposium held in November 2002 at the annual meeting of the
      American College of Toxicology.

PMID- 14680992
TI  - Oral (drinking water) developmental toxicity study of ammonium perchlorate in
      Sprague-Dawley rats.
AB  - A developmental toxicity study was conducted with ammonium perchlorate (AP) in
      the drinking water at doses of 0.0, 0.01, 0.1, 1.0, and 30.0 mg/kg-day beginning
      14 days before cohabitation and continuing through sacrifice. Twenty-four
      rats/group were cesarean-sectioned on day of gestation (DG) 21 and fetuses
      examined for visceral and skeletal alterations. An additional 16 litters/group
      were sacrificed on DG 21 for maternal and fetal serum TSH, T(3), and T(4)
      (thyroid-stimulating hormone, triiodothyronine, and thyroxine) levels and thyroid
      histopathology. Clinical and necropsy observations, body weights, feed and water
      consumption, and cesarean-sectioning parameters were comparable among the groups
      with only delays in ossification observed in the 30 mg/kg-day group. Maternal
      thyroid weights were increased in the 30.0 mg/kg-day group. Decreased colloid was
      present in male and female fetal thyroids in the 1.0 and 30.0 mg/kg-day groups.
      Maternal TSH was increased and T(4) was decreased at all levels, and T(3) was
      reduced at 30.0 mg/kg-day. Fetal TSH was increased at 1.0 and 30.0 mg/kg-day,
      T(4) was reduced at 30.0 mg/kg-day, and T(3) was decreased at all levels. The
      maternal no-observable-adverse-effect level (NOAEL) was 1.0 mg/kg-day; exposures
      of 30.0 mg/kg-day increased absolute and relative maternal thyroid weights and
      histopathology findings. The developmental NOAEL was 1.0 mg/kg-day; developmental
      delays in ossification occurred in the 30.0 mg/kg-day group. The colloid
      depletion in the thyroids and increased TSH and decreased T(3) and T(4) levels at
      lower exposures were considered adaptive and not adverse. No adverse effects on
      development at occurred levels that did not cause maternal toxicity. AP is not a
      selective developmental toxicant.

PMID- 14680993
TI  - Issues in chemical and biological terrorism.
AB  - This manuscript describes the overview presented at the 23rd Annual Meeting of
      the American College of Toxicology in 2002. Although it is recognized that
      weapons of mass destruction that can be used against our military and civilian
      populations include chemical, biological, radiological, and nuclear (CBRN)
      agents, this overview is limited primarily to chemical and biological (CB)
      agents. The issues of CB terrorism are discussed in terms of When, What, How, and
      Who. The US Army has been providing chemical and biological solutions since 1917,
      and has since 1996 applied these solutions to homeland defense and domestic
      preparedness. The use of chemical and biological agents as terrorist weapons both
      in the United States and elsewhere in the world is reviewed. The CB threat
      spectrum is presented, as is the further categorization of biological threat
      agents by the Centers for Disease Control and Prevention (CDC). In addition, the
      CB agents considered to be a potential threat to our water supply are also
      presented. These are agents that are water soluble, stable, and resistant to
      water treatment and/or disinfection. The overview concludes with the
      chronological accomplishments of ECBC since 1917.

PMID- 14680994
TI  - [Re: "Widespread arsenic contamination of soils in residential areas and public
      spaces: an emerging regulatory or medical crisis"].

PMID- 14680995
TI  - [Re: "Comparison of in vivo (Draize method) and in vitro (Corrositex assay)
      dermal corrosion values for selected industrial chemicals"].

PMID- 14680996
TI  - Effects of upper respiratory tract illnesses in a working population.
AB  - The aim of the present study was to assess the impact of upper respiratory tract
      illnesses on efficiency at work. This was done using the 'after-effect' technique
      with measurements being taken before and after work and the difference between
      these giving an indication of efficiency over the day. All of the volunteers (N =
      48) were tested when healthy to provide baseline data for simple reaction time
      and mood. When volunteers developed an upper respiratory tract illness (URTI)
      they (N = 16) repeated the procedure. Those who remained healthy over a three
      month period (N = 32) were recalled as healthy controls. In addition to the
      performance test and mood ratings the volunteers kept a sleep log and also rated
      how demanding the day had been and how much effort they had put in. The results
      showed that those with URTIs had slower reaction times and a more negative mood
      both before and after work. Illness did not have an effect on ratings of demand
      and effort. Those who were ill reported greater sleep disturbance but this could
      not account for the impaired performance or negative mood states. These results
      suggest that upper respiratory illnesses may impair performance and well-being at
      work.

PMID- 14680997
TI  - Ergonomics and biology of spinal rotation.
AB  - Spinal rotation, though being a very common motion of the body, is poorly
      understood. Furthermore, this motion and the extent of its development is unique
      to the human. Beyond the extent of its need in common activities, spinal rotation
      is a destabilizating motion for an inherently unstable structure. Spinal rotation
      has been argued to be an essential feature for an efficient bipedal gait. Also,
      it provides leverage to the upper extremities in delivering a forceful impact. An
      artificial restriction/elimination of spinal rotation resulted in significantly
      shorter stride length, slower walking velocity, and higher energy consumption in
      walking (p < 0.05). Spinal rotation also decreases the amount of force the spinal
      muscles can generate (to 25% of spinal extension). However, its extensive
      employment in industrial activities has been associated with 60.4% of back
      injuries. It is further stated that the amount of scientific information
      currently available is inadequate to biomechanically model the spinal response in
      a working environment. For example, when the spine is pre-rotated, a further
      rotation in the direction of pre-rotation decreases the force production
      significantly (p < 0.01) and increases the EMG activity significantly (p < 0.01)
      but the pattern changes with effort in the opposite direction. This and other
      properties (described in the paper) render biomechanical models inadequate.
      Muscle activation pattern and neuromotor behaviour of spinal muscles in
      flexion/extension and rotation of the spine are significantly different from each
      other (p < 0.01). The localized fatigue in different spinal muscles in the same
      contraction is significantly different and has been called differential fatigue.
      Finally, the trunk rotation, being pivotal for bipedal locomotion has brought
      many back problems to the human race.

PMID- 14680998
TI  - School furniture and the user population: an anthropometric perspective.
AB  - The purpose of this study was to determine the relationship between reported
      spinal symptoms in an adolescent student population, and the match between their
      individual anthropometric dimensions and their school furniture. The hypothesis
      was that students who were too large or too small for their school furniture,
      i.e. with anthropometric measurements furthest from the group whose anthropometry
      was the 'best fit' with the furniture, would have a higher frequency of reported
      symptoms. From data collected from 1269 schoolchildren, reported spinal symptoms
      and anthropometric measures were examined. Stature measures were divided into
      quartiles. A standard government issue school chair and desk was measured and the
      anthropometric quartile of the population having the 'best fit' with the
      furniture was identified using standard ergonomics recommendations. Odds ratios
      were calculated for spinal symptoms reported within each quartile group. The
      first quartile group (the smallest students) was identified as having the 'best
      fit' with the school furniture. An overall higher odds of reporting low back pain
      was noted in students with anthropometric dimensions in the fourth quartile (the
      tallest students). While it is acknowledged that there is a multifactorial nature
      of causality of adolescent spinal symptoms, it is contended that the degree of
      mis-match between child anthropometry and school furniture set-up should be
      further examined as a strong and plausible associate of adolescent low back pain.

PMID- 14680999
TI  - Joint angles of isocomfort for female subjects based on the psychophysical
      scaling of static standing postures.
AB  - This study investigated the joint angles of isocomfort (JAIs) for females based
      on the psychophysical scalings for static standing postures held for 60 s, which
      were obtained in a laboratory experiment. The subjects were instructed to rate
      their comfort levels for varyious joint postures by using the free modulus method
      of magnitude estimation. The comfort scores for the joint postures and the
      related verbal comfort categories were subjected to regression analysis in order
      to obtain the JAIs corresponding to verbal categories. The results showed that
      the JAIs were significantly different depending upon the joints and joint
      postures investigated (p < 0.01), and that the JAIs for female subjects were
      significantly different than those for males (p < 0.01) which had been obtained
      in an earlier study (Kee and Karwowski, 2001). Compared to the corresponding
      range of joint motion values, the JAIs for hip postures were the smallest of all
      joint postures dealt with in this study, while those for the neck were the
      largest of all postures, which means that hip postures are more stressful than
      any other joint posture. Based on this study, it is recommended that the gender
      based JAI values should be used for design applications.

PMID- 14681001
TI  - Abstracts from XIX Nordic Congress of Cardiology. Odense, Denmark, June 4-6,
      2003.

PMID- 14681000
TI  - The physical demands upon (Dutch) fire-fighters in relation to the maximum
      acceptable energetic workload.
AB  - The aim of this study was to assess the tasks and activities that make physical
      demands on Dutch fire-fighters and to compare them with a guideline related to
      the development of excessive fatigue. The occupational physical demands on Dutch
      fire-fighters were assessed by conducting a task analysis during 85 24-h shifts.
      While workplace observations on the duration and frequency of physical tasks and
      activities were recorded, the heart rate was measured. This was then used to
      calculate the heart rate reserve percentage (%HRR) for predefined working
      periods, tasks and activities during 24-h shifts. The findings indicate that
      actual fire-fighting during 24-h shifts is characterised by a low frequency of
      incidents, a short 'turn-out' time, short tasks, and activities with a moderate
      to occasionally high energetic workload. Two tasks which sometimes occur in
      actual fire-fighting exceeded the guideline on energetic workload. The conclusion
      was that, though the number of incidents and the occupational demands are low
      during 24-h shifts, the peak loads for these two tasks are energetically high and
      could lead to excessive fatigue. Consequently, attention may need to be paid to
      health surveillance for persons exposed to such energetic peak loads, the
      development of physical and medical selection procedures, training, and workplace
      adjustments.

PMID- 14681002
TI  - Moray revisited: high-priority affective stimuli and visual search.
AB  - Previous research offers conflicting suggestions about whether "high-priority"
      verbal stimuli such as an individual's own name or emotionally charged words
      automatically grab attention and/or can be detected without the usual capacity
      limitations. Nine experiments investigated this issue, using visual search
      through displays of words. In speeded search tasks, the subject's own name was
      detected more quickly than other targets, but in no case were search slopes flat
      enough to suggest parallel search or "pop-out". Further, names were not found to
      be unusually potent distractors. Emotionally charged words were neither more
      readily detected as targets nor more potent as distractors than neutral words. A
      comparison of observers' accuracy in searching briefly exposed simultaneous vs.
      successive displays provided further evidence that search for "high-priority"
      word targets is subject to the same severe capacity limitations as those that are
      found with search for neutral words.

PMID- 14681003
TI  - Individual differences in deductive reasoning.
AB  - Three studies are reported, which examined individual differences in deductive
      reasoning as a function of intellectual ability and thinking style. Intellectual
      ability was a good predictor of logical performance on syllogisms, especially
      where there was a conflict between logic and believability. However, in the first
      two experiments there was no link between ability and performance on indicative
      selection tasks, in sharp contrast to previous research. This correlation did,
      however, return in the final study. Our data are consistent with the claim that
      the correlation with logical accuracy on abstract selection tasks is found
      primarily with participants of relatively high ability. At lower levels,
      pragmatically cued responses are given but those of slightly higher ability
      divorce the rule from the scenario and respond consistently (though incorrectly)
      across problems. Self-report questionnaires were generally poor predictors of
      performance, but a measure of the ability to generate alternative representations
      proved an excellent predictor. These results are consistent with a mental models
      approach to reasoning and also have implications for the debate about human
      rationality.

PMID- 14681004
TI  - Differential effects of prime-probe duration on positive and negative location
      priming: Evidence for opponent facilitatory and inhibitory influences in priming
      tasks.
AB  - A series of four spatial localization experiments is reported that examined the
      effects of display duration and presentation mode on positive and negative
      priming using an attended-repetition and an ignored-repetition paradigm,
      respectively. Experiment 1 showed larger positive priming with response-dependent
      than with 150 ms display durations while negative priming remained unaffected.
      Experiments 2-4 were performed to further elucidate the effects of prime-probe
      durations. Data suggest largely independent effects of prime and probe duration
      on priming effects. Manipulation of prime duration affected facilitation due to
      repetition of the prime distractor location as well as inhibitory effects
      associated with ignored repetition. Furthermore, anticipated probe duration
      modulated the effectiveness of inhibition of return. Findings are discussed
      within a framework proposing two major components of priming effects--a stimulus
      driven or automatic component, and a strategic component related to the
      participant's expectations towards the probe.

PMID- 14681005
TI  - Anticipated action effects affect the selection, initiation, and execution of
      actions.
AB  - This study investigated the impact of contingent action effects on response
      production. In Experiment 1 responses of varying intensity were initiated faster
      when contingently followed by auditory effects of corresponding rather than of
      noncorresponding intensity. This response-effect (R-E) compatibility influence
      was robust with respect to practice, and it was not due to persisting influences
      of preceding R-E episodes. These results support the conclusion that R-E
      compatibility reflects the impact of anticipatory effect representations in
      response production. Experiment 2 showed that anticipatory effect codes have an
      impact on early processes of response production (response selection) as well as
      on processes that immediately precede overt responding (response initiation).
      Finally, they also influence the way the actions are physically performed
      (response execution). The results support and specify ideo-motor theories of
      action control that assume movements to be controlled by anticipations of their
      sensorial effects.

PMID- 14681006
TI  - Environmental context-dependent recognition memory effects: an examination of ICE
      model and cue-overload hypotheses.
AB  - The ICE model account (e.g., Murnane & Phelps, 1993; Murnane, Phelps, & Malmberg,
      1999) of environmental context (EC)-dependent recognition memory is described,
      and new predictions concerning the effect of multiple presentation ECs are
      derived. Experiment 1 tested the ICE model predictions in relation to predictions
      derived from the cue-overload hypothesis (e.g., Watkins, 1979). In addition, the
      sensitivity of recognition reaction time (RT) as a measure of EC-dependent memory
      effects was examined. Minimal support was obtained for the ICE model, but greater
      support was provided for the cue-overload hypothesis. In Experiment 2, further
      manipulations were employed to test ICE model predictions and the cue-overload
      hypothesis, with relevance to the mental reinstatement and outshining hypotheses.
      Again support for the cue-overload hypothesis was obtained, and an EC
      reinstatement effect with RTs was detected. The ICE model is considered in
      respect of these findings.

PMID- 14681007
TI  - Verbal working memory and on-line syntactic processing: evidence from self-paced
      listening.
AB  - Two experiments investigated the relationship between performance on standard
      tests of verbal working-memory and the on-line construction of syntactic form. In
      Experiment 1, working-memory was measured in 100 college students on a version of
      the Daneman and Carpenter (1980) reading-span task, and online syntactic
      processing was assessed using a self-paced listening task with four sentence
      types. In Experiment 2, working-memory was measured in 48 college students on two
      versions of the reading-span task and two other tests of verbal working-memory,
      and on-line syntactic processing was assessed using the self-paced listening task
      with an additional sentence type. In both experiments, there was no relationship
      between working-memory capacity and the increase in processing time seen for the
      on-line construction of syntactic form for either syntactically more complex or
      syntactically simpler sentences. The results indicate that the capacity of the
      working-memory system that is measured by standard working-memory tests does not
      determine the efficiency of on-line syntactic processing. They are consistent
      with the view that the working-memory system used for parsing is at least
      partially separate from that measured by traditional measures of working-memory
      capacity.

PMID- 14681008
TI  - Inspecting pictures for information to verify a sentence: Eye movements in
      general encoding and in focused search.
AB  - When we see combinations of text and graphics, such as photographs and their
      captions in printed media, how do we compare the information in the two
      components? Two experiments used a sentence-picture verification task in which
      statements about photographs of natural scenes were read in order to make a
      true/false decision about the validity of the sentence, and in which eye
      movements were recorded. In Experiment 1 the sentence and the picture were
      presented concurrently, and objects and words could be inspected in any order. In
      Experiment 2 the two components were presented one after the other, either
      picture first or sentence first. Fixation durations on pictures were
      characteristically longer than those on sentences in both experiments, and
      fixations on sentences varied according to whether they were being encoded as
      abstract propositions or as coreferents of objects depicted in a previously
      inspected picture. The decision time data present a difficulty for existing
      models of sentence verification tasks, with an inconsistent pattern of
      differences between true and false trials.

PMID- 14681012
TI  - An update on connexin genes and their nomenclature in mouse and man.
AB  - Gap junctions, composed of connexin protein subunits, allow direct communication
      through conduits between neighboring cells. Twenty and twenty-one members of the
      connexin gene family are likely to be expressed in the mouse and human genome,
      respectively, 19 of which can be grouped into sequence-orthologous pairs. Their
      gene structure appears to be relatively simple. In most cases, an untranslated
      exon1 is separated by an intron of different lengh from exon2 that includes the
      uninterrupted coding region and the 3'-untranslated region. However, there are
      several exceptions to this scheme, since some mouse connexin genes contain
      different 5'-untranslated regions spliced either in an alternative and/or
      consecutive manner. Additionally, in at least 3 mouse and human connexin genes
      (mCx36, mCx39, mCx57 and hCx31.3, hCx36, as well as hCx40.1) the reading frame is
      spliced together from 2 different exons. So far, there are two nomenclatures to
      classify the known connexin genes: The "Gja/Gjb" nomenclature, as it is currently
      adopted by the NCBI data base, contains some inconsistencies compared to the "Cx"
      nomenclature. Here we suggest some minor corrections to co-ordinate the "Gja/Gjb"
      nomenclature with the "Cx" nomenclature. Furthermore, this short review contains
      an update on phenotypic correlations between connexin deficient mice and patients
      bearing mutations in their orthologous connexin genes.

PMID- 14681013
TI  - Tetracysteine genetic tags complexed with biarsenical ligands as a tool for
      investigating gap junction structure and dynamics.
AB  - Gap junctions (GJ) are defined as contact regions between two adjacent cells
      containing tens to thousands of closely packed membrane channels. Cells
      dynamically modulate communication through GJ by regulating the synthesis,
      transport and turnover of these channels. Previously, we engineered a recombinant
      connexin43 (Cx43) by genetically appending a small tetracysteine peptide motif
      containing the sequence -Cys-Cys-Xaa-Xaa-Cys-Cys- to the carboxy terminus of Cx43
      (Cx43-TC) (3). Cx43-TC was stably expressed in HeLa cells and was specifically
      labeled by exposing the cells to membrane-permeant non-fluorescent ligands, such
      as FlAsH (a fluorescein derivative) and ReAsH (a resorufin derivative). Direct
      correlation of live cell images with high resolution EM detection was possible
      because bound ReAsH not only becomes fluorescent, but can also be used to
      initiate the photoconversion of diaminobenzidine (DAB) that causes the localized
      polymerization of an insoluble osmiophilic precipitate then visible by EM. Cx43
      TC GJ's could be labeled with ReAsH and photooxidized to give selectively stained
      channels. Here, how the development of these tetracysteine tags complexed with
      appropriate ligands are useful for experiments spanning resolution ranges from
      light microscopy to electron tomography to molecular purification and detection
      is described.

PMID- 14681014
TI  - Projection structure of full length connexin 43 by electron cryo-crystallography.
AB  - We previously used electron cryo-crystallography to determine the three
      dimensional structure of recombinant gap junction channels formed by a C-terminal
      truncation mutant of Cx43 (11). The dodecameric channel is formed by the end-to
      end docking of two hexameric connexons, each comprised of 24 transmembrane alpha
      helices. We have now generated two-dimensional crystals of the recombinant, full
      length channel, as well as crystals in which the C-tail has been completely
      removed by trypsin digestion. Projection density maps at 7.5 A resolution closely
      resemble our previous analysis of the C-terminal truncation mutant (9). A
      difference map between the full length and trypsin-treated channels suggests that
      there are small but significant shifts in protein density upon removal of the C
      tail.

PMID- 14681015
TI  - Pore-lining residues identified by single channel SCAM studies in Cx46
      hemichannels.
AB  - The substituted cysteine accessibility method was applied to single Cx46
      hemichannels to identify residues that participate in lining the aqueous pore of
      channels formed of connexins. Criteria for assignment to the pore included
      reactivity to sulfydryl-specific methanethiosulfonate (MTS) reagents from both
      sides of an open hemichannel and observable effects on open channel properties.
      We demonstrate reactivity to MTS reagents over a stretch of seventeen amino
      acids, D51 through L35, that constitute segments of E1 and TM1. Qualitatively,
      the nature of the effects caused by the Cys substitutions alone and their
      modification with MTS reagents of either charge indicate side chain valence is
      most influential in determining single channel properties with D51 and L35
      defining the extracellular and intracellular limits, respectively, of the
      identified pore-lining region. A number of Cys substitutions beyond L35 in TM1
      caused severe alterations in hemichannel function and precluded assignment to the
      pore. Although all six subunits can be modified by smaller MTS reagents,
      modifications appear limited to fewer subunits with larger reagents.

PMID- 14681016
TI  - Association of connexin43 with a receptor protein tyrosine phosphatase.
AB  - Connexin-43(Cx43)-based gap junctional communication is transiently inhibited by
      certain G protein-coupled receptor agonists, including lysophosphatidic acid,
      endothelin and thrombin. Our previous studies have implicated the c-Src protein
      tyrosine kinase in mediating closure of Cx43 based gap junctions. Pervanadate, an
      inhibitor of protein tyrosine phosphatases, mimics activated Src in inhibiting
      Cx43 gap junctional communication, apparently by promoting tyrosine
      phosphorylation of the Cx43 C-terminal tail. However, the identity of the protein
      tyrosine phosphatase(s) that may normally prevent Src-induced gap junction
      closure is unknown. Receptor-like protein tyrosine phosphatases that mediate
      homotypic cell-cell interaction are attractive candidates. Here we show that
      receptor protein tyrosine phosphatase mu (RPTPmu) interacts with Cx43 in diverse
      cell systems. We find that the first catalytic domain of RPTPmu binds to Cx43.
      Our results support a model in which RPTPmu, or a closely related protein
      tyrosine phosphatase, interacts with the regulatory C-terminal tail of Cx43 to
      prevent Src-mediated closure of Cx43 gap junctional channels.

PMID- 14681017
TI  - Kinetics of protein-protein interactions of connexins: use of enzyme linked
      sorbent assays.
AB  - Determination of the protein-protein interactions of connexins has become a
      rapidly expanding field of research. While there are multiple methods of
      determining the identity of binding partners, determination of the strengths of
      interactions is not as simple. Here we describe the use of the in vitro method
      Enzyme Linked Sorbent Assay (ELSA) to compare binding affinities of known protein
      partners for Connexin43. We used the binding of Cx43 Carboxyl Terminal domain to
      the PDZ-2 domain of Zonula Occludens-1 and to the SH3 domain of c-Src. In the
      ELSA assay we found that while the binding of the SH3 domain of c-Src is pH
      dependent, the interaction of the PDZ domain of ZO-1 is not. These data confirm
      findings using Surface Plasmon Resonance (1) and indicate that ELSA can be a
      useful tool in determining the kinetics of protein-protein interactions.

PMID- 14681018
TI  - Fusion of GFP to the carboxyl terminus of connexin43 increases gap junction size
      in HeLa cells.
AB  - The pattern of gap junctional coupling between cells is thought to be important
      for the proper function of many types of tissues. At present, little is known
      about the molecular mechanisms that control the size and distribution of gap
      junctions. We addressed this issue by expressing connexin43 (Cx43) constructs in
      HeLa cells, a connexin-deficient cell line. HeLa cells expressing exogenously
      introduced wild-type Cx43 formed small, punctate gap junctions. By contrast,
      cells expressing Cx43-GFP formed large, sheet-like gap junctions. These results
      suggest that the GFP tag, which is fused to the carboxyl terminus of Cx43, alters
      gap junction size by masking the carboxyl terminal amino acids of Cx43 that
      comprise a zonula occludins-1 (ZO-1) binding site. We are currently testing this
      hypothesis using deletion and dominant-negative constructs that directly target
      the interaction between Cx43 and ZO-1.

PMID- 14681019
TI  - Identification of connexin-43 interacting proteins.
AB  - Connexin-43 (Cx43), the most ubiquitously expressed vertebrate gap junction
      protein, has been shown to interact directly with Zonula Occludens-1 (ZO-1).
      Although several potential functions have been proposed for the ZO-1/Cx43
      interaction, the role that ZO-1 and other Cx43-interacting partners play in the
      regulation of Cx43 trafficking, assembly, gating and turnover are not well
      understood. We believed a thorough analysis and classification of other Cx43
      interacting proteins might help us to understand and better test these roles. We
      approached this question by utilizing Tandem Mass Spectrometry (MS/MS) analysis
      to identify proteins from normal rat kidney whole cell lysates that could
      interact with the C-terminal region of Cx43. Comparison against protein sequence
      databases identified 19 probable protein matches, including kinases,
      phosphatases, membrane receptors, cell signaling molecules and scaffolding
      proteins. We have further characterized some of these interacting proteins,
      including Zonula Occludens-2 (ZO-2), via western blotting and "pull down"
      experiments. Further in vitro/in vivo analysis of these interacting proteins will
      help in our understanding of the global role of connexins in regulating
      development, cell metabolism and growth.

PMID- 14681020
TI  - Cellular distribution of innexin 1 and 2 gap junctional channel proteins in
      epithelia of the Drosophila embryo.
AB  - Invertebrate gap junctions are composed of Innexin channel proteins that are
      structurally and functionally analogous to the connexins in vertebrates. In situ
      hybridization experiments have shown that most of the eight known innexin genes
      in Drosophila are expressed in a complex and overlapping temporal and spatial
      profile, with several members showing high levels of expression in developing
      epithelia of the embryo. To further study the cellular roles of Innexins, we have
      generated antibodies against Innexins 1 and 2 and studied their protein
      distribution in the developing embryo. We find that both Innexins are co
      expressed in a number of epithelial tissues including the epidermis, the gut and
      the salivary glands. On the cellular level, we find both proteins localized to
      the membranes of epithelial cells. Immunohistochemical analysis using cell
      polarity markers indicates that Innexin 1 is predominantly localized to the baso
      lateral domain of epithelial cells, basal to septate junctions. In contrast, we
      find a variable positioning of Innexin 2 along the apico-basal axis of epithelial
      cells depending on the type of tissue and organ. Our findings suggest that the
      distribution of Innexin channel proteins to specific membrane domains of
      epithelial cells is regulated by tissue specific factors during the development
      of epithelia in the fly embryo.

PMID- 14681021
TI  - Transcriptional and translational regulation of zebrafish connexin 55.5
      (zf.Cx.55.5) and connexin 52.6 (zf.Cx52.6).
AB  - Zebrafish connexin 55.5 (zf.Cx55.5) and connexin 52.6 (zf.Cx52.6) show highly
      restricted expression patterns in the nervous system. Both connexins are confined
      to subsets of neurons in the fish retina. In order to get initial answers to the
      questions of pattern definition in neuronal subsets, we elucidated molecular
      mechanisms responsible for their expression. Different upstream DNA fragments
      were subcloned into a pGL3-basic vector and transiently transfected in HeLa and
      N2A cells. Luciferase activity showed the presence of two putative promoter
      elements in zfCx55.5 and a promoter element in zfCx52.6 that showed different
      promoter activities in HeLa and N2A cells. Moreover, fusion constructs of
      zfCx55.5 with EGFP revealed the presence of a new isoform with an additional
      short exon I.

PMID- 14681022
TI  - The voltage gates of connexin channels are sensitive to CO(2).
AB  - Cx45 channel sensitivity to CO(2), transjunctional voltage (V(j)) and inhibition
      of calmodulin (CaM) expression was tested in oocytes by dual voltage-clamp. Cx45
      channels are very sensitive to V(j) and close preferentially by the slow gate,
      likely the same as the chemical gate. With CO(2)-induced drop in junctional
      conductance (G(j)), the speed of V(j)-dependent inactivation of junctional
      current (I(j)) and V(j) sensitivity increased. With 40 mV V(j), the tau of single
      exponential I(j) decay reversibly decreased by approximately 40% with CO(2), and
      G(j steady state)/G(j peak) decreased multiphasically, indicating that kinetics
      and V(j) sensitivity of chemical/slow-V(j) gating are altered by changes in
      [H(+)](i) and/or [Ca(2+)](i). With 15 min exposure to CO(2), G(j) dropped to 0%
      in controls and by approximately 17% following CaM expression inhibition;
      similarly, V(j) sensitivity decreased significantly. This indicates that the
      speed and sensitivity of V(j)-dependent inactivation of Cx45 channels are
      increased by CO(2), and that CaM plays a role in gating. Cx32 channels behaved
      similarly, but the drop in both G(j steady state)/G(j peak) and tau with CO(2)
      matched more closely that of G(j peak). In contrast, sensitivity and speed of
      V(j) gating of Cx40 and Cx26 channels decreased, rather than increased, with
      CO(2) application.

PMID- 14681023
TI  - Open pore block of connexin26 and connexin32 hemichannels by neutral, acidic and
      basic glycoconjugates.
AB  - The mechanisms of molecular discrimination by connexin channels are of acute
      biological and medical importance. The availability of affinity or open-pore
      blocking reagents for reliable and specific study of the connexin permeability
      pathway, would make possible the rigorous cellular and physiological studies
      required to inform, in molecular terms, the underlying role of intercellular
      communication pathways in development and disease. Previous work utilized a
      series of glucosaccharides labeled with an uncharged fluorescent aminopyridine
      (PA-) group to establish steric constraints to permeability through connexin
      hemichannels. In that work, the smallest probe permeable through homomeric Cx26
      and heteromeric Cx26-Cx32 channels was the PA-disaccharide, and the smallest
      probe permeable through homomeric Cx32 channels was the PA-trisaccharide. The
      larger impermeable probes did not block permeation of the smaller probes.
      Building on this work, a new set of glucosaccharide probes was developed in which
      the label was one of a homologous series of novel anthranilic acid derivatives
      (ABG) that carry negative or positive formal charge or remain neutral at
      physiological pH. When the PA-label of the smallest impermeant PA-derivatized
      oligosaccharides was replaced by ABG label, the resulting probes acted as
      reversible, high-affinity inhibitors of large molecule permeation through
      connexin pores in a size and connexin-specific manner.

PMID- 14681024
TI  - Functioning of cx43 hemichannels demonstrated by single channel properties.
AB  - It has been suggested that the opening of non-junctional connexin 43 (Cx43)
      hemichannels may play a role in cell physiology, but some workers doubt the
      reality of hemichannel openings. Here we show data on unitary conductance and
      voltage gating properties demonstrating that Cx43 hemichannels can open. Membrane
      depolarization > +60 mV induced single hemichannel currents in HeLa cells
      expressing Cx43 or Cx43 with enhanced green fluorescent protein attached to the
      carboxy terminal (Cx43-EGFP). The conductance of single hemichannels was
      approximately 220 pS, about twice that of the cell-cell channels. Cx43 and Cx43
      EGFP hemichannels exhibited slow transitions (>5 ms) between closed and fully
      open states. Cx43 hemichannels also exhibited fast transitions (<1 ms) between
      the fully open state and a substate of approximately 75 pS. Similar gating was
      described for their respective cell-cell channels. No comparable single channel
      activity was detected in the parental (nontransfected cells) or HeLa cells
      expressing Cx43 fused at the amino terminal with EGFP (EGFP-Cx43). The latter
      chimera was inserted into the surface and formed plaques, but did not express
      functional hemichannels or cell-cell channels. These data convincingly
      demonstrate the opening of Cx43 hemichannels.

PMID- 14681025
TI  - Connexin channels, connexin mimetic peptides and ATP release.
AB  - Connexin hemichannels, that is, half gap junction channels (not connecting
      cells), have been implicated in the release of various messengers such as ATP and
      glutamate. We used connexin mimetic peptides, which are, small peptides mimicking
      a sequence on the connexin subunit, to investigate hemichannel functioning in
      endothelial cell lines. Short exposure (30 min) to synthetic peptides mimicking a
      sequence on the first or second extracellular loop of the connexin subunit
      strongly supressed ATP release and dye uptake triggered by either intracellular
      InsP(3) elevation or exposure to zero extracellular calcium, while gap junctional
      coupling was not affected under these conditions. The effect was dependent on the
      expression of connexin-43 in the cells. Connexin mimetic peptides thus appear to
      be interesting tools to distinguish connexin hemichannel from gap junction
      channel functioning. In addition, they are well suited to further explore the
      role of connexins in cellular release or uptake processes, to investigate
      hemichannel gating and to reveal new unknown functions of the large conductance
      hemichannel pathway between the cell and its environment. Work performed up to
      now with these peptides should be re-interpreted in terms of these new findings.

PMID- 14681026
TI  - Hemichannels formed by connexin 43 play an important role in the release of
      prostaglandin E(2) by osteocytes in response to mechanical strain.
AB  - Osteocytes embedded in the matrix of bone are mechanosensory cells that translate
      strain into signals and regulate bone remodeling. Our previous studies using
      osteocyte-like MLO-Y4 cells have shown that fluid flow shear stress (FFSS)
      increases connexin (Cx) 43 protein expression, prostaglandin E(2) (PGE(2))
      release, and intercellular coupling, and PGE(2) is an essential mediator between
      FFSS and gap junctions. However, the role of Cx43 in the release of PGE(2) in
      response to FFSS is unknown. Here, the FFSS-loaded MLO-Y4 cells with no or few
      intercellular channels released significantly more PGE(2) per cell than those
      cells at higher densities. Antisense Cx43 oligonucleotides and 18 beta
      glycyrrhetinic acid, a specific gap junction and hemichannel blocker,
      significantly reduced PGE(2) release by FFSS at all cell densities tested,
      especially cells at the lowest density without gap junctions. FFSS, fluid flow
      conditioned medium, and PGE(2) increased the activity of dye uptake. Moreover,
      FFSS induced Cx43 to migrate to the surface of the cell; this surface expressed
      Cx43 developed resistance to Triton-X-100 solublization. Our results suggest that
      hemichannels formed by Cx43, instead of intercellular channels, are likely to
      play a predominant role in the release of intracellular PGE(2) in response to
      FFSS.

PMID- 14681027
TI  - Distribution of connexin50 channels and hemichannels in lens fibers: a structural
      approach.
AB  - A detailed understanding of the mechanisms regulating cell-to-cell communication
      in the lens necessitates information about the distribution and density of Cx46
      and Cx50 in their native cellular environment. These isoforms constitute the
      extensive pathway between the lens surface and the interior, helping to maintain
      its striking optical properties. To identify Cx50 channels and hemichannels in
      the plasma membrane and to differentiate between them, immuno-freeze-fracture
      labeling (FRIL) with immuno-gold particles in used. In equatorial lens fibers,
      the Cx50-gold complexes label gap junctions at high densities and non-junctional
      plasma membranes at lower densities. Small depressions in the non-junctional
      plasma membrane labeled by the gold-complexes most likely represent points of
      hemichannel insertion. Measurement of the width of the extra-cellular space
      separating adjacent plasma membranes indicates that the gold complexes in the gap
      junctions represent Cx50 channels and those in the non-junctional plasma
      membrane, Cx50 hemichannels. Estimates of their densities indicate that the
      channels are at least one order of magnitude more numerous than the hemichannels.
      Therefore, in lens fibers, Cx50 hemichannels are inserted via exocytosis and are
      rapidly assembled into channels assembled in gap junction plaques.

PMID- 14681028
TI  - A potential role for cx43-hemichannels in staurosporin-induced apoptosis.
AB  - To address the role of gap junction hemichannels in apoptosis, the cell death
      induced by staurosporine (ST) was evaluated in wild type HeLa cells (HeLa-WT) and
      transfectants expressing either full-length connexin43 (HeLa-Cx43) or a C
      terminal truncation of Cx43 (HeLa-DeltaCT). Cell death was measured with
      fluorescence-activated cell sorting (FACS), both DNA and nuclear fragmentation
      methods and assays for PARP and caspase 3. The ST-mediated cell death was
      accelerated in HeLa-Cx43 cells compared to HeLa-WT and HeLa-DeltaCT. To determine
      why HeLa-Cx43 cells were more susceptible to ST, the phosphorylation state and
      the localization of Cx43 protein within cells were examined using specific Cx43
      antibodies. The phosphorylated forms of Cx43 were sharply reduced in HeLa-Cx43
      cells treated with ST. Moreover, in ST-treated HeLa-Cx43 cells, Cx43 was mainly
      observed at the cell surface. In contrast, the truncated form of Cx43 found in
      HeLa-DeltaCT cells, which lacks many of the normal phosphorylation sites, was
      observed in the cytosol with ST treatment. To examine the hemichannels in the
      plasma membranes of ST-treated HeLa-Cx43 cells, several dye uptake methods using
      carboxyfluorescein and propidium iodide were employed. While the number of
      fluorescent cells did not change in HeLa-WT and HeLa-DeltaCT cells with ST
      treatment, the number of fluorescent HeLa-Cx43 cells increased more than ten
      fold. These results indicate that the increases in cell surface Cx43 seen with
      immunofluorescence and the elevated hemichannel activities detected with dye
      uptake could help explain the accelerated cell death observed in ST-treated HeLa
      Cx43 cells.

PMID- 14681030
TI  - Selective effect of PDGF on connexin43 versus connexin40 comprised gap junction
      channels.
AB  - The goals of the current study were to determine whether the conductance of Cx40
      and Cx40-Cx43 mixed composition junctions was regulated by platelet-derived
      growth factor (PDGF)-activated signaling cascades, to ascertain the minimum
      number of Cx43 subunits/connexon required to confer PDGF sensitivity, and to
      identify specific residues in Cx43 required for this regulation. Junctional and
      channel conductances (g(j) and gamma(j), respectively) were determined for
      Cx40/Cx40, Cx43/Cx43, Cx40/Cx43, and Cx40-Cx43/Cx40-Cx43 mixed composition
      channels. PDGF had no effect on g(j) in Cx40/Cx40 pairs, but decreased g(j) in
      the remaining combinations by 53% (Cx43/Cx43), 48% (Cx40/Cx43), 41% (4:1
      Cx40:Cx43 expression ratio) and 24% (10:1 Cx40:Cx43 expression ratio). Based on
      the predicted connexin composition of channels in cells expressing Cx40 and Cx43
      at either 4:1 or 10:1 ratios, these decreases in g(j) suggest that a single
      subunit of Cx43 is sufficient to confer PDGF sensitivity. The effect of PDGF on
      g(j) involved a decrease in both gamma(j) and Po and required serine 368 in the C
      terminus. These data implicate protein kinase C as the mediator of the PDGF
      effect and strongly suggest that acute regulation of gap junction function by
      PDGF-activated signaling cascades is conferred by low levels of expression of a
      sensitive connexin in cells that otherwise express insensitive connexins.

PMID- 14681029
TI  - Src signaling links mediators of inflammation to Cx43 gap junction channels in
      primary and transformed CFTR-expressing airway cells.
AB  - Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) is
      associated with recurrent pulmonary infections and inflammation. We previously
      reported that tumor necrosis factor (TNF)-alpha decreases gap junction
      connectivity in cell lines derived from the airway epithelium of non-cystic
      fibrosis (non-CF) subjects, a mechanism that was defective in cells derived from
      CF patients, and identified the tyrosine kinase c-Src as a possible bridge
      between TNF-alpha and Cx43. To examine whether this modulation also takes place
      in primary epithelial cells, the functional expression of Cx43 was studied in non
      CF and CF airway cells, obtained from surgical polypectomies and turbinectomies,
      which were grown either on culture dishes or permeable filters. Expression of
      Cx43 was detected by immunofluorescence on cells grown under both culture
      conditions. Non-CF and CF airway cells also showed intercellular diffusion of
      Lucifer Yellow. Dye coupling was rapidly abolished in non-CF cells in the
      presence of TNF-alpha, lipopolysaccharide and lysophosphatidic acid, and could be
      prevented by tyrphostin47, an inhibitor of Src tyrosine kinases. This down
      regulation, however, was not detected in CF airway cells. These data indicate
      that CFTR dysfunction is associated with altered Src signaling, resulting in the
      persistence of gap junction connectivity in primary and transformed CF airway
      cells.

PMID- 14681031
TI  - PKC-dependent phosphorylation may regulate the ability of connexin43 to inhibit
      DNA synthesis.
AB  - Phosphorylation affects several biological functions of connexin43 (Cx43),
      although its role on Cx43-mediated inhibition of DNA synthesis is not known.
      Previous studies showed increased Cx43 phosphorylation on serine in response to
      growth factor stimulation of cardiomyocytes, mediated by protein kinase C-epsilon
      (PKCepsilon). Here we report that activation of PKCepsilon is also necessary for
      stimulation of cardiomyocyte DNA synthesis and mitosis. We have investigated the
      participation of specific serine residues that are putative PKC targets in
      producing phosphorylated Cx43 species and also in regulating DNA synthesis in
      cardiomyocytes. Interference with the PKC signaling system and/or the
      phosphorylation of specific amino-acids of Cx43 may allow regulation of the
      mitogenic response.

PMID- 14681032
TI  - Maintaining connexin43 gap junctional communication in v-Src cells does not alter
      growth properties associated with the transformed phenotype.
AB  - Loss of connexin expression and/or gap junctional communication (GJC) has been
      correlated with increased rates of cell growth in tumor cells compared to their
      normal communication-competent counterparts. Conversely, reduced rates of cell
      growth have been observed in tumor cells that are induced to express exogenous
      connexins and re-establish GJC. It is not clear how this putative growth
      suppressive effect of the connexin proteins is mediated and some data has
      suggested that this function may be independent of GJC. In mammalian cells that
      express v-Src, connexin43 (Cx43) is phosphorylated on Tyr247 and Tyr265 and this
      results in a dramatic disruption of GJC. Cells that express a Cx43 mutant with
      phenylalanine mutations at these tyrosine sites form functional gap junctions
      that, unlike junctions formed by wild type Cx43, remain functional in cells that
      co-express v-Src. These cells still appear transformed; however, it is not known
      whether their ability to maintain GJC prevents the loss of growth restraints that
      confine "normal" cells, such as the inability to grow in an anchorage-independent
      manner or to form foci. In these studies, we have examined some of the growth
      properties of cells with Cx43 gap junctions that remain communication-competent
      in the presence of the co-expressed v-Src oncoprotein.

PMID- 14681033
TI  - Opposing effects of nitric oxide on different connexins expressed in the vascular
      system.
AB  - Gap junctions--clusters of intercellular channels built by connexins (Cx)--are
      thought to be important for vascular cell functions such as differentiation,
      control of tone, or growth. In the vascular system, gap junctions can be formed
      by four different connexins (Cx37, Cx40, Cx43 and Cx45). The permeability of
      these connexin-formed gap junctions determines the amount of intercellular
      coupling and can be modulated by several vasoactive substances such as
      prostacyclin or nitric oxide (NO). We demonstrate here that NO has specific
      effects on certain connexins. Using two different techniques--injection of a
      fluorescent dye in single cells as well as detection of the de novo formation of
      gap junctions by a flow cytometry based technique--we found that NO decreases the
      functional coupling in Cx37 containing gap junctions whereas it increases the de
      novo formation of gap junctions containing Cx40. We conclude that NO, in addition
      to its known vasomotor effects, has a novel role in controlling intercellular
      coupling resulting in opposing effects depending on the specific connexin
      expressed in the cells.

PMID- 14681034
TI  - Development of a cell model for functional and structural analysis of connexin co
      expression: achieving homogeneous and inducible expression of multiple connexins
      in stable transfectants.
AB  - We set out to develop an in vitro cell model in which connexins 43, 40 and 45 are
      co-expressed in the same combinations as found in different sub-types of
      cardiomyocyte in vivo, using inducible promoters of the Tet-Off and Ecdysone
      systems. In initial studies, a heterogeneous pattern of gene expression was
      observed. To achieve homogeneous expression, an Internal Ribosome Entry Site
      (IRES) sequence was employed, ensuring that a single mRNA coded for connexin and
      antibiotic resistance. We then constructed plasmids that combine the inducibility
      of the Tet-Off and Ecdysone systems with the homogeneous expression given by the
      IRES constructs. These were demonstrated to give inducible and homogeneous
      expression. By using the reporter gene, Enhanced Green Fluorescent Protein
      (EGFP), it was further shown in the Tet-Off system that expression of the
      transfected gene was modulated homogeneously in all cells when induction was
      repressed. The cell model is now at a suitable stage of development for
      investigation of the functional correlates of the distinctive connexin co
      expression found in different regions of the heart.

PMID- 14681035
TI  - Differential oligomerization of endoplasmic reticulum-retained
      connexin43/connexin32 chimeras.
AB  - To examine early events in connexin oligomerization, we made connexin constructs
      containing a C-terminal di-lysine based endoplasmic reticulum (ER)
      retention/retrieval signal (HKKSL). Previously, we found that both Cx32-HKKSL and
      Cx43-HKKSL were retained in the ER. However, Cx32-HKKSL oligomerized into
      hexameric hemichannels, but Cx43-HKKSL was retained as an apparent monomer. To
      define elements that prevent Cx43-HKKSL oligomerization in the ER, we made a
      series of HKKSL-tagged Cx43/Cx32 chimeras. When expressed by HeLa cells, some
      chimeras were retained in the ER as apparent monomers, whereas others
      oligomerized in the ER. To date, the second and third transmembrane domains and
      the cytoplasmic loop domain provide the minimal sufficient Cx43 element to
      inhibit ER oligomerization.

PMID- 14681036
TI  - A carboxyl terminal domain of connexin43 is critical for gap junction plaque
      formation but not for homo- or hetero-oligomerization.
AB  - We have initiated a series of experiments to analyze the biosynthesis and
      oligomerization of Cx43 in cells containing other connexins through the
      expression of site-directed mutants and chimeric connexin polypeptides. Here we
      report studies concerning a mutant of Cx43 (Cx43tr) that has been truncated after
      amino acid 251 to remove most of the Cx43 carboxy-terminal region. In stably
      transfected HeLa cells, full length Cx43 localized primarily to appositional
      membranes while much more Cx43tr was observed in the cytoplasm. Both Cx43 and
      Cx43tr showed similar oligomerization profiles based on centrifugation through
      sucrose gradients. HeLaCx43tr cells showed limited transfer of microinjected
      Lucifer Yellow but did show electrical coupling. Co-expression of Cx43tr with
      Cx43 or Cx45 led to Cx43tr localization at appositional membranes and co
      localization with the other connexins. Moreover, cells co-expressing Cx43tr with
      Cx43 or Cx45 showed extensive intercellular dye coupling. Thus, Cx43tr was able
      to oligomerize and form functional channels when expressed alone or with a
      compatible connexin, but it only formed plaques when co-expressed. These results
      suggest that the carboxyl tail of Cx43 is not important for oligomerization, but
      they implicate critical residues in the formation of gap junction plaques.

PMID- 14681037
TI  - Degradation of connexins from the plasma membrane is regulated by inhibitors of
      protein synthesis.
AB  - Little is known about the mechanism and regulation of connexin turnover from the
      plasma membrane. We have used a combination of cell surface biotinylation,
      immunofluorescence microscopy, and scrape-load dye transfer assays to investigate
      the effect of the protein synthesis inhibitor cycloheximide on connexin43 and
      connexin32 after their transport to the plasmalemma. The results obtained
      demonstrate that cycloheximide inhibits the turnover of connexins from the
      surface of both gap junction assembly-deficient and -efficient cells. Moreover,
      cell surface connexin saved from destruction by cycloheximide can assemble into
      long-lived, functional gap junctional plaques. These findings support the concept
      that downregulation of connexin degradation from the plasma membrane can serve as
      a mechanism to enhance gap junction-mediated intercellular communication.

PMID- 14681038
TI  - Following tracks of hemichannels.
AB  - It has been suggested that plasma membrane-bound hemichannels perform
      physiological and pathophysiological functions per se. Such functions require the
      presence of hemichannels on the cell surface and their accessibility to the
      extracellular environment for at least some limited period of time. We have
      previously shown that hemichannels can be labeled by means of antibodies directed
      to an external loop domain of connexin (Cx) 43. We now provide evidence that
      trafficking of hemichannel vesicles can be visualized upon binding of a labeled
      homophilic peptide corresponding to a region of the first extracellular loop
      (EL1) of Cx43. In vivo imaging was performed after labeling hemichannels from the
      extracellular site with a mimetic peptide tagged with a fluorochrome (Alexa-546).
      Using a Cx43-CFP transfected HeLa cell line for incubation with the mimetic
      peptide, a significant number of double-labeled vesicles were found inside the
      cells. This double labeling indicates that a portion of Cx43 within the cell had
      accessed the cell surface as hemichannels where it bound to the peptide and was
      subsequently endocytosed. Pulse labeling with the peptide showed a decrease in
      the number of dual-labeled vesicles over time, indicating degradation and/or
      concurrent recycling of hemichannel vesicles.

PMID- 14681039
TI  - The inner ear contains heteromeric channels composed of cx26 and cx30 and
      deafness-related mutations in cx26 have a dominant negative effect on cx30.
AB  - Cx26 and cx30 co-localize in tissues of the mammalian cochlea. Transfected HeLa
      cells were used to examine interactions between cx26 and cx30 and the effects on
      cx30 of four point mutations in cx26 that are associated with dominantly
      inherited hearing loss--W44S, G59A, D66H and R75W. When co-expressed, wtcx26 and
      wtcx30 trafficked to the same gap junction plaques. Cells transferred neurobiotin
      but not Lucifer Yellow, which passes freely through cx26 channels, suggesting
      cx30 affects the properties of cx26. G59A and D66H had a perinuclear localization
      when expressed alone but trafficked to the membrane when co-expressed with cx30.
      Co-expression of W44S, G59A or R75W with cx30, significantly reduced neurobiotin
      transfer in comparison with cells expressing cx30 only. These results indicate
      that cx26 and cx30 can oligomerize to form heteromeric connexons and demonstrate
      a dominant negative effect of some cx26 mutants on cx30. Immunogold labeling of
      thin sections of the cochlea showed both cx26 and cx30 distributed evenly on both
      sides of individual gap junction profiles. Immunoprecipitation of cochlear
      membrane proteins, isolated by procedures that preserve connexons, with either
      cx30 or cx26 antibodies precipitated both cx26 and cx30. Following co-injection
      of Lucifer Yellow and neurobiotin into individual supporting cells of the organ
      of Corti in cochlear slices, neurobiotin transferred to many cells, but Lucifer
      Yellow was retained in the injected cell. These observations are consistent with
      junctions composed of cx26/cx30 heteromeric connexons in the cochlea. The
      functional disruption caused by some cx26 mutations upon such heteromeric
      channels may underlie the non-syndromic nature of their effects on hearing.

PMID- 14681040
TI  - Cellular mechanisms of mutant connexins in skin disease and hearing loss.
AB  - It has been demonstrated that distinct germline mutations within four connexin
      (Cx) genes, Cx26, Cx30, Cx31, and Cx30.3, underlie hearing loss and/or epidermal
      disease. Here, we describe two Cx26 mutations associated with skin disease. With
      the goal of understanding the mechanism(s) of Cx-associated human disease and how
      different mutations within the same Cx protein can result in different disorders,
      we performed a number of functional analyses investigating the cellular effects
      of disease-associated Cx mutations in keratinocytes and other cell types.
      Epidermal disease-associated proteins studied were primarily cytoplasmic with
      limited trafficking ability. FACS analysis of WT and mutant EGFP-Cx31 transfected
      keratinocytes revealed a high percentage of cell death associated with the skin
      disease-associated mutant Cx31 proteins.

PMID- 14681041
TI  - Transport and function of cx26 mutants involved in skin and deafness disorders.
AB  - We examined the subcellular localization and function of several Cx26 mutants
      that exhibit both sensorineural deafness and various skin disease phenotypes. To
      facilitate these aims, all Cx26 mutants were tagged at the carboxyl-terminal with
      green fluorescent protein (GFP), which has previously been shown not to affect
      Cx26 transport, assembly or function. In this article we focus on two point
      mutations (R75W and DeltaE42) that occur in the first extracellular loop region
      of Cx26, a region hypothesized to be critical for correct hemichannel docking
      between contacting cells. In gap junctional intercellular communication (GJIC)
      deficient HeLa cells, both R75W-GFP and DeltaE42-GFP were transported to the cell
      surface and assembled into gap junction-like structures. Neither R75W-GFP nor
      DeltaE42-GFP formed gap junctions that were permeable to Lucifer Yellow
      suggesting they are loss-of-function mutations. We also examined the phenotype of
      these two mutations in a rat epidermal keratinocyte (REK) cell line that is
      capable of undergoing differentiation. Using antibodies against several members
      of the connexin family reportedly expressed by epidermal keratinocytes, we found
      these cells endogenously expressed Cx43 and Cx26 but not Cx30, Cx32, or Cx37.
      When expressed in REK cells, similar to in HeLa cells, R75W-GFP and DeltaE42-GFP
      were assembled at the cell surface into structures that resembled gap junctions.
      Future experiments will examine the effect of the Cx26 mutants on the function
      and differentiation of these epidermal keratinocytes.

PMID- 14681042
TI  - The effects of a mutant connexin 26 on epidermal differentiation.
AB  - To elucidate the mode of action of dominant mutant connexins in causing inherited
      skin diseases, transgenic mice were produced that express the true Vohwinkel
      syndrome-associated mutant Cx26 (D66H), from a keratin 10 promoter, specifically
      in the suprabasal epidermal keratinocytes. Following birth, the transgenic mice
      developed keratoderma similar to that of human carriers of Cx26 (D66H).
      Expression of the transgene resulted in a loss of Cx26 and Cx30 at intercellular
      junctions of epidermal keratinocytes and accumulation of these connexins in the
      cytoplasm. Injection of primary mouse keratinocytes with Lucifer Yellow showed no
      difference in terms of dye spreading between transgenic and non transgenic
      keratinocytes in vitro. Expression of the mutant Cx26 (D66H) did not interfere
      with the formation of the epidermal water barrier during late embryonic
      development. Attempts to produce transgenic mice expressing the wild type form of
      Cx26 from the K10 promoter failed to produce viable animals although transgenic
      embryos were recovered at days 9 and 12 of gestation, suggesting that the
      transgene might be embryonic lethal.

PMID- 14681043
TI  - Mice lacking connexin45 conditionally in cardiac myocytes display embryonic
      lethality similar to that of germline knockout mice without endocardial cushion
      defect.
AB  - The gap junction protein connexin45-deficient (Cx45-KO) mice die shortly after
      the hearts begin to beat. In addition to the heart defect, they also show
      defective vascular development which may be closely related with the cardiac
      phenotype. Therefore, we created mice whose floxed-Cx45 locus could be removed
      conditionally. We utilized cardiac alpha-actin-Cre transgenic mice to investigate
      the specific cardiac muscular function of Cx45 in vivo. The resultant conditional
      mutants were lethal, showing conduction block similar to that of the Cx45-KO
      mice. Unlike Cx45-KO, development of the endocardial cushion was not disrupted in
      the conditional mutants. X-gal staining was detected in the embryonic cardiac
      myocytes as a hallmark of Cre-loxP mediated floxed-Cx45 deletion. These results
      reconfirm the requirement of Cx45 for developing cardiac myocytes. These also
      indicate that establishing the first contractions is a crucial task for the early
      hearts.

PMID- 14681044
TI  - Effects of the new antiarrhythmic peptide ZP123 on epicardial activation and
      repolarization pattern.
AB  - Antiarrhythmic peptides such as AAP10 (Gly-Ala-Gly-4Hyp-Pro-Tyr-CONH(2)) have
      antiarrhythmic properties related to their stimulatory effect on gap junctional
      coupling. However, most of these peptides are not stable in enzymatic environment
      which limits studies with these compounds in vivo. ZP123 is a new antiarrhythmic
      peptide constructed using a retro-all-D-amino acid design of the AAP10 template
      (Ac-D-Tyr-D-Pro-D-4Hyp-Gly-D-Ala-Gly-NH(2)). The aim of this study was to compare
      the effects of AAP10 and ZP123 on epicardial activation and repolarization
      patterns in isolated perfused rabbit hearts. In addition, we tested the effect of
      these compounds on PKC activation in cultured HeLa-Cx43 cells. Rabbit hearts were
      perfused according to the Langendorff technique with Tyrode solution at constant
      pressure (70 cm H(2)O). After 45 min equilibration, either AAP10 (n = 7) or ZP123
      (n = 7) was infused intracoronarily in concentrations of 0.1, 1, 10, 100, and
      1000 nM (15 min for each concentration) in the presence of 0.05% bovine serum
      albumine. 256 AgCl electrodes were attached to the hearts surface and connected
      to the inputs of a 256 channel mapping system in a unipolar circuit (4
      kHz/channel, 0.04 mV vertical resolution, 1 mm spatial resolution). For each
      electrode the activation and repolarization timepoint were determined. We found
      that both peptides significantly reduced epicardial dispersion by a maximum of
      about 20% thereby enhancing the homogeneity of epicardial action potential
      duration, while the action potential duration itself was not affected. The beat
      to-beat variability of the epicardial activation pattern was stabilized by both
      peptides as compared to an untreated time-control series. Other parameters such
      as LVP, CF, heart rate, or total activation time were not effected by either of
      the peptides. In a second protocol, rectangular pulses were delivered to the back
      wall and the propagation velocity was determined longitudinal and transversal to
      the fiber axis. We found an increase in both longitudinal and transversal
      conduction velocity. Using a commercial PKC assay on HeLa-Cx43 cells we found
      that 50 nM AAP10 and 50 nM ZP123 increased activity by 99 +/- 6% and 146 +/- 54%,
      respectively. The PKC activation induced by either of these compounds was
      completely blocked using the selective PKCalpha inhibitor GCP54345. We conclude
      that AAP10 and ZP123 have similar effects in vitro, but the superior enzymatic
      stability of ZP123 makes this compound the preferred substance for in vivo
      studies of antiarrhythmic peptides.

PMID- 14681045
TI  - Role of connexin37 and connexin40 in vascular development.
AB  - Mice lacking both connexin37 (Cx37) and connexin40 (Cx40), gap junction proteins
      expressed in vascular endothelium, die perinatally with pronounced vascular
      abnormalities. Early vasculogenesis proceeds normally, but by E18.5 Cx37(-/
      )Cx40(-/-) animals display vessel dilatation and congestion as well as localized
      hemorrhages in skin, testis, intestines, and lungs. Abnormal vascular channels
      are present in the testis, often forming cavernous hemangioma-like defects.
      Unusually large, distended vessels are also present in the submucosa and lamina
      propria of the intestine. Ablation of Cx40 has a greater effect on endothelial
      dye-transfer than ablation of Cx37, and the effect of Cx40 ablation is age
      dependent. Only in embryonic aortas lacking both Cx37 and Cx40 is there a
      complete loss of endothelial coupling. Surprisingly, elimination of Cx40 results
      in a large drop in aortic endothelial Cx37 on western blots, and deletion of Cx37
      also reduces endothelial Cx40 levels. In contrast, in the medial layer, both Cx37
      and Cx43 increase when Cx40 is ablated. These studies indicate that Cx37 and Cx40
      are collectively critical for endothelial communication and provide evidence of
      an important role for gap junctions in vascular development. In addition, Cx37
      and Cx40 appear to be mutually dependent on each other for normal expression in
      vascular endothelium.

PMID- 14681046
TI  - Connexin26 regulates the expression of angiogenesis-related genes in human breast
      tumor cells by both GJIC-dependent and -independent mechanisms.
AB  - We previously reported that over-expression of connexins in mammary tumor cells
      retarded tumor growth in vivo in the absence of appreciable gap junction
      formation, highlighting a possible connexin-linked, but gap junctional
      intercellular communication (GJIC)-independent mechanism. In the current study,
      we engineered GJIC-deficient MDA-MB-435 human breast tumor cells to express a
      chimeric Cx26 where the green fluorescent protein was fused to the amino-terminal
      of Cx26 (GFP-Cx26). Characterization of this chimeric protein revealed that GFP
      Cx26 assembled into non-functional gap junction-like clusters that were
      impermeable to Lucifer Yellow. In contrast, expression of wild-type Cx26 or Cx26
      tagged at the carboxy terminal with yellow fluorescent protein, efficiently
      rescued GJIC in these tumor cells. Interestingly, by screening 96 tumor-related
      genes, we observed that the expression of Cx26 or GFP-Cx26 in the tumor cells up
      regulated both the transcription and the translation of thrombospondin-1 (TSP-1),
      an anti-angiogenic molecule. Affymetrix array analysis extended the list of Cx26
      or GFP-Cx26 regulated genes by ten candidates including connective tissue growth
      factor (CTGF), another angiogenesis-related gene. CTGF mRNA and protein levels
      were found to be down-regulated by both Cx26 and GFP-Cx26. Thus, our data
      indicates that Cx26 regulates angiogenesis-related molecules by mechanisms that
      are both GJIC-dependent and -independent.

PMID- 14681047
TI  - Dual benefit of reduced Cx43 on atherosclerosis in LDL receptor-deficient mice.
AB  - Paracrine cell-to-cell interactions are crucial events during atherogenesis,
      however, little is known on the role of gap junctional communication during this
      process. We recently demonstrated increased expression of Cx43 in intimal smooth
      muscle cells and in a subset of endothelial cells covering the shoulder of
      atherosclerotic plaques. The purpose of this study was to examine the role of
      Cx43 in the development of atherosclerosis in vivo. Atherosclerosis-susceptible
      LDL receptor-deficient (LDLR(-/-)) mice were intercrossed with mice heterozygous
      for Cx43 (Cx43(+/-) mice). Male mice with normal (Cx43(+/+)LDLR(-/-)) or reduced
      (Cx43(+/-)LDLR(-/-)) Cx43 level of 10 weeks old were fed a cholesterol-rich diet
      (1.25%) for 14 weeks. Both groups of mice showed similar increases in serum
      lipids and body weight. Interestingly, the progression of atherosclerosis was
      reduced by 50% (P < 0.01) in the thoraco-abdominal aorta and in the aortic roots
      of Cx43(+/-)LDLR(-/-) mice compared with Cx43(+/+)LDLR(-/-) littermate controls.
      In addition, atheroma in Cx43(+/-)LDLR(-/-) mice contained fewer inflammatory
      cells and exhibited thicker fibrous caps with more collagen and smooth muscle
      cells, important features associated, in human, with stable atherosclerotic
      lesions. Thus, reducing Cx43 expression in mice provides beneficial effects on
      both the progression and composition of the atherosclerotic lesions.

PMID- 14681048
TI  - Astrocyte and oligodendrocyte connexins of the glial syncytium in relation to
      astrocyte anatomical domains and spatial buffering.
AB  - Astroctyes express a set of three connexins (Cx26, Cx30, and Cx43) that are
      contained in astrocyte-to-astrocyte (A/A) gap junctions; oligodendrocytes express
      a different set of three connexins (Cx29, Cx32, and Cx47) that are contained in
      the oligodendrocyte side of necessarily heterotypic astrocyte-to-oligodendrocyte
      (A/O) gap junctions, and there is little ultrastructural evidence for gap
      junction formation between individual oligodendrocytes. In addition, primarily
      Cx29 and Cx32 are contained deeper in myelin sheaths, where they form autologous
      gap junctions at sites of uncompacted myelin. The presence of six connexins in
      macroglial cell populations has revealed unprecedented complexity of potential
      connexin coupling partners, and with restricted deployment of gap junctional
      intercellular communication (GJIC) within the "pan-glial" syncytium. New
      implications for the organization and regulation of spatial buffering mediated by
      glial GJIC are derived from recent observations of the existence of separate
      astrocyte anatomical domains, with only narrow regions of overlap between
      astrocyte processes at domain borders. Thus, widespread spatial buffering in the
      CNS may occur not successively through a multitude of processes arising from
      different astrocytes, but rather in a more orderly fashion from one astrocyte
      domain to another via intercellular coupling that occurs only at restricted
      regions of overlap between astrocyte domains, augmented by autocellular coupling
      that occurs within each domain.

PMID- 14681049
TI  - Neurons and brain macrophages regulate connexin expression in cultured
      astrocytes.
AB  - Neurons and brain macrophages (BM), respectively, increase and inhibit gap
      junctional communication (GJC) and connexin expression in cultured astrocytes.
      Thus, in brain diseases and injuries, neuronal death associated with the BM
      activation may decrease GJC in astrocytes and therefore have a physiopathological
      relevance.

PMID- 14681050
TI  - Neuroprotective role of astrocytic gap junctions in ischemic stroke.
AB  - The role of astrocytic gap junctions in ischemia remains controversial. Several
      studies support that astrocytic gap junctions play a role in the spread of
      hypoxic injury, while other reports have demonstrated that blocking astrocytic
      gap junctions increases neuronal death. Using a stroke model on animals in which
      the astrocytic gap junction protein connexin43 (Cx43) was compromised, we
      explored the neuroprotective role of astrocytic gap junctions. A focal brain
      stroke was performed on heterozygous Cx43 null [Cx43(+/-)] mice, wild type
      [Cx43(+/+)] mice, astrocyte-directed Cx43 deficient [Cx43(fl/ fl)/hGFAP-cre] mice
      (here designated as Cre(+) mice), and their corresponding controls [Cx43(fl/fl)]
      (here designated as Cre(-) mice). Four days following stroke, ischemic lesions
      were measured for size and analyzed immunohistochemically. Stroke volume was
      significantly larger in Cx43(+/-) and Cre(+) mice compared to Cx43(+/+) and Cre(
      ) mice, respectively. Apoptosis as detected by TUNEL labeling and caspase-3
      immunostaining was amplified in Cx43(+/-) and Cre(+) mice compared to their
      control groups. Furthermore, increased inflammation as characterized by the
      immunohistochemical staining of the microglial marker CD11b was observed in the
      Cre(+) mice penumbra. Astrocytic gap junctions may reduce apoptosis and
      inflammation in the penumbra following ischemic insult, suggesting that coupled
      astrocytes fulfill a neuroprotective role under ischemic stroke conditions.

PMID- 14681051
TI  - Short-range functional interaction between connexin35 and neighboring chemical
      synapses.
AB  - Auditory afferents terminating as mixed, electrical, and chemical, synapses on
      the goldfish Mauthner cells constitute an ideal experimental model to study the
      properties of gap junctions in the nervous system as well as to explore possible
      functional interactions with the other major form of interneuronal communication-
      chemically mediated synapses. By combining confocal microscopy and freeze
      fracture replica immunogold labeling (FRIL), we found that gap junctions at these
      synapses contain connexin35 (Cx35), the fish ortholog of the neuron-specific
      human and mouse connexin36 (Cx36). Conductance of gap junction channels at these
      endings is known to be dynamically modulated by the activity of their co
      localized chemically mediated glutamatergic synapses. By using simultaneous pre-
      and postsynaptic recordings at these single terminals, we demonstrate that such
      functional interaction takes place in the same ending, within a few micrometers.
      Accordingly, we also found evidence by confocal and FRIL double-immunogold
      labeling that the NR1 subunit of the NMDA glutamate receptor, proposed to be a
      key regulatory element, is present at postsynaptic densities closely associated
      with gap junction plaques containing Cx35. Given the widespread distribution of
      Cx35- and Cx36-mediated electrical synapses and glutamatergic synapses, our data
      suggest that the local functional interactions observed at these identifiable
      junctions may also apply to other electrical synapses, including those in
      mammalian brain.

PMID- 14681052
TI  - Multiple neuronal connexins in the mammalian retina.
AB  - Gap junctions are abundant in the mammalian retina and many neuronal types form
      neural networks. Several different neuronal connexins have now been identified in
      the mammalian retina. Cx36 supports coupling in the AII amacrine cell network and
      is essential for processing rod signals. Cx36 is probably also responsible for
      photoreceptor coupling. Horizontal cells appear to be extensively coupled by
      either Cx50 or Cx57. These results indicate that multiple neuronal connexins are
      expressed in the mammalian retina and that different cell types express different
      connexins.

PMID- 14681053
TI  - Cx36 involvement in insulin secretion: characteristics and mechanism.
AB  - Gap junctions connect the pancreatic beta-cells which produce insulin. To
      investigate their function, we have first determined that these junctions are
      made of Cx36. We have then tested the effect of changing the expression of Cx36,
      and other connexin isoforms, and have found that Cx36 modulates insulin
      secretion. In view of the prominent role of cytosolic Ca(2+) in this secretion,
      we have monitored this cation, and have found that its handling is altered in
      populations of insulin-producing cells lacking Cx36. The data identify a first
      molecular link between Cx36 and the stimulus-secretion pathway leading to insulin
      secretion.

PMID- 14681054
TI  - Role of the p38 MAP-kinase signaling pathway for Cx32 and claudin-1 in the rat
      liver.
AB  - Liver regeneration and cholestasis are associated with adaptive changes in
      expression of gap and tight junctions through signal transduction. The roles of
      stress responsitive MAP-kinase, p38 MAP-kinase, in the signaling pathway for gap
      junction protein, Cx32, and tight junction protein, claudin-1, were examined in
      rat liver in vivo and in vitro, including regeneration following partial
      hepatectomy and cholestasis after common bile duct ligation. Changes in the
      expression and function of Cx32 and claudin-1 in hepatocytes in vivo were studied
      using the p38 MAP-kinase inhibitor SB203580. Following partial hepatectomy and
      common bile duct ligation, down-regulation of Cx32 protein was inhibited by
      SB203580 treatment. Up-regulation of claudin-1 protein was enhanced by SB203580
      treatment after partial hepatectomy but not common bile duct ligation. However,
      no change of the Ki-67 labeling index (which is a marker for cell proliferation)
      in the livers treated with SB203580, was observed compared to that without
      SB203580 treatment. In primary cultures of rat hepatocytes, however, treatment
      with a p38 MAP-kinase activator, anisomycin, decreased Cx32 and claudin-1 protein
      levels. p38 MAP-kinase may be an important signaling pathway for regulation of
      gap and tight junctions in hepatocytes. Changes of gap and tight junctions during
      liver regeneration and cholestasis are shown to be in part controlled via the p38
      MAP-kinase signaling pathway and are independent of cell growth.

PMID- 14681055
TI  - Development of mice with osteoblast-specific connexin43 gene deletion.
AB  - Genetic deficiency of Cx43 in vivo causes skeletal developmental defects,
      osteoblast dysfunction and perinatal lethality. To determine the role of Cx43 in
      the adult skeleton, we developed two models of osteoblast-specific Cx43 gene
      deletion using Cre mediated replacement of a "floxed" Cx43 allele with a LacZ
      reporter gene. Cre recombinase expression in osteoblasts was driven by either the
      osteocalcin OG2 promoter or the 2.3 kb fragment of the Colalpha1(I) promoter.
      Homozygous Cx43(fl/fl) mice, in which the Cx43 coding region is flanked by two
      loxP sites, were crossed with Cre expressing mice in a heterozygous Cx43-null
      background [Cx43(+/-); Colalpha1(I)-Cre or Cx43(+/-); OG2-Cre]. Cx43 gene
      ablation was demonstrated in tissues by selective X-gal staining of cells lining
      the endosteal surface, and in cultured osteoblastic cells from calvaria using
      different approaches. Although no LacZ expression was observed in proliferating
      calvaria cells, before osteoblast differentiation begins, post-proliferative
      cells isolated from conditional knockout mice [Cx43(fl/-); Colalpha1(I)-Cre or
      Cx43(fl/-); OG2-Cre] developed strong LacZ expression as they differentiated, in
      parallel to a progressive disappearance of Cx43 mRNA and protein abundance
      relative to controls. Selective Cre mediated Cx43 gene inactivation in bone
      forming cells will be useful to determine the role of Cx43 in adult skeletal
      homeostasis and overcome the perinatal lethality of the conventional null model.

PMID- 14681056
TI  - Presence and importance of connexin43 during myogenesis.
AB  - We analyzed the expression of connexin(Cx)43 in proliferating and differentiating
      C(2)C(12) cells and in myoblasts obtained from newborn mice. Cx43 was present in
      both cell types and under both conditions. The functional role of gap junctional
      communication (GJC) during terminal differentiation was evaluated in C(2)C(12)
      myoblasts in the presence or absence of the gap junction blocker 18beta
      glycyrrhetinic acid (beta-GA). Differentiation was temporally analyzed through
      myogenin expression, activity of creatine kinase (CK), and yield of
      multinucleated cells. In cells treated with beta-GA, the CK activity and myotube
      formation were reversibly blocked. While in control cultures positive myogenin
      expression was seen in cell clusters, in beta-GA treated cultures the myogenin
      immunoreactivity was detected in few, preferentially sparse cells. The role of
      Cx43 during terminal differentiation was evaluated in cultures of myoblasts
      obtained from Cx43(Cre-ER(T)/fl) transgenic mice. Inducible deletion of Cx43 was
      obtained upon activation of Cre-ER(T) via 4-OH-tamoxifen applications. Cx43
      deletion led to a drastic decrease in myogenin expression at 24 h of
      differentiation as compared to myoblasts from control mice. Our results indicate
      that Cx43-containing gap junctions are required for normal skeletal muscle
      terminal differentiation. These channels might provide a pathway for the
      intercellular transfer of signals involved in myogenesis.

PMID- 14681057
TI  - Heparin modulates integrin-mediated cellular adhesion: specificity of
      interactions with alpha and beta integrin subunits.
AB  - Heparin is known to influence the growth, proliferation, and migration of
      vascular cells, but the precise mechanisms are unknown. We previously
      demonstrated that unfractionated heparin (UH) binds to the platelet integrin
      alpha(IIb)beta(3), and enhances ligand binding. To help define the specificity
      and site(s) of heparin-integrin interactions, we employed the erythroleukemic
      K562 cell line, transfected to express specific integrins (alpha(v)beta(3),
      alpha(v)beta(5), and alpha(IIb)beta(3)). By comparing K562 cells expressing a
      common alpha subunit (Kalpha(v)beta(3), Kalpha(v)beta(5)) with cells expressing a
      common beta subunit (Kalpha(v)beta(3), Kalpha(IIb)beta(3)), we observed that
      heparin differentially modulated integrin-mediated adhesion to vitronectin. UH at
      0.5-7.5 microg/ml consistently enhanced the adhesion of beta(3) expressing cells
      (Kalpha(v)beta(3),Kalpha(IIb)beta(3)). In contrast, UH at 0.5-7.5 microg/ml
      inhibited Kalpha(v)beta(5) adhesion. Experiments using integrin-blocking
      antibodies, appropriate control ligands, and nontransfected native K562 cells
      revealed that heparin's actions were mediated by the specific integrins under
      study. Preincubation of heparin with Kalpha(v)beta(3) cells enhanced adhesion,
      while preincubation of heparin with the adhesive substrate (vitronectin) had
      minimal effect. There was a structural specificity to heparin's effect, in that a
      low molecular weight heparin and chondroitin sulfate showed significantly less
      enhancement of adhesion. These findings suggest that heparin's modulation of
      integrin-ligand interactions occurs through its action on the integrin. The
      inhibitory or stimulatory effects of heparin depend on the beta subunit type, and
      the potency is dictated by structural characteristics of the glycosaminoglycan.

PMID- 14681058
TI  - Focal contact clustering in osteoblastic cells under mechanical stresses:
      microgravity and cyclic deformation.
AB  - We quantitatively compared vinculin-related adhesion parameters in osteoblastic
      cells submitted to two opposing mechanical stresses: low deformation and
      frequency strain regimens (stretch conditions) and microgravity exposure (relaxed
      conditions). In both ROS 17/2.8 cells and rat primary osteoblastic cells, 1%
      cyclic deformations at 0.05 Hz for 10 min per day for seven days stimulated cell
      growth compared to static culture conditions, while relaxed ROS cells
      proliferated in a similar way to static cultures (BC). We studied the short-term
      (up to 24 h) adaptation of focal contact reorganization under these two
      conditions. Cyclic deformation induced a biphasic response comprising the
      formation of new focal contacts followed by clustering of these focal contacts in
      both ROS cells and primary osteoblasts. Microgravity exposure induced a reduction
      in focal contact number and clustering in ROS cells. To evaluate whether the
      proliferation (stretch) or survival (relaxed) status of ROS cells influences
      focal contact organization, we inhibited the ERK proliferative-dependent pathway.
      Inhibition of proliferation by PD98059 was partially reversed, but not fully
      restored by stretch. Stretch-induced clustering of vinculin-positive contacts
      also persisted in the presence of PD98059, whereas the increase in focal contact
      number was abolished. In conclusion, we show that focal contacts are
      mechanoeffectors, and we suggest that their morphologic organization might serve
      as a discriminant functional parameter between survival and proliferation status
      in ROS 17/2.8 osteoblastic cells.

PMID- 14681059
TI  - Vitronectin's basic domain is a syndecan ligand which functions in trans to
      regulate vitronectin turnover.
AB  - During the process of tissue remodeling, vitronectin (Vn) is deposited in the
      extracellular matrix where it plays a key role in the regulation of pericellular
      proteolysis and cell motility. In previous studies we have shown that
      extracellular levels of vitronectin are controlled by receptor-mediated
      endocytosis and that this process is dependent upon vitronectin binding to
      sulfated proteoglycans. We have now identified vitronectin's 12 amino acid "basic
      domain" which is contained within the larger 40 amino acid heparin binding
      domain, as a syndecan binding site. Recombinant vitronectins representing wild
      type vitronectin (rVn) and vitronectin with the basic domain deleted (rVnDelta347
      358) were prepared in a baculoviral expression system. The rVn as well as a
      glutathione S-transferase (GST) fusion protein, consisting of vitronectin's 40
      amino acid heparin binding domain (GST-VnHBD), exhibited dose dependent binding
      to HT-1080 cell surfaces, which was attenuated following deletion of the basic
      domain. In addition, GST-VnHBD supported both HT-1080 and dermal fibroblast cell
      adhesion, which was also dependent upon the basic domain. Similarly, ARH-77 cells
      transfected with syndecans -1, -2, or -4, but not Glypican-1, adhered to GST
      VnHBD coated wells, while adhesion of these same cells was lost following
      deletion of the basic domain. HT-1080 cells were unable to degrade rVnDelta347
      358. Degradation of rVnDelta347-358 was completely recovered in the presence of
      GST-VnHBD but not in the presence of GST-VnHBDDelta347-358. These results
      indicate that turnover of soluble vitronectin requires ligation of vitronectin's
      basic domain and that this binding event can work in trans to regulate
      vitronectin degradation.

PMID- 14681061
TI  - Susceptibility of Clostridium perfringens strains from broiler chickens to
      antibiotics and anticoccidials.
AB  - Clostridium perfringens strains isolated in 2002 from the intestines of broiler
      chickens from 31 different farms located in Belgium were tested for
      susceptibility to 12 antibiotics used for therapy, growth promotion or prevention
      of coccidiosis. All strains were uniformly sensitive to the ionophore antibiotics
      monensin, lasalocid, salinomycin, maduramycin and narasin. All were sensitive to
      avilamycin, tylosin and amoxicillin, while flavomycin (bambermycin) showed low or
      no activity. Chlortetracycline and oxytetracycline were active at very low
      concentrations, but low-level acquired resistance was detected in 66% of the
      strains investigated. Fifty percent of these strains carried the tetP(B)
      resistance gene, while the tet(Q) gene was detected in only one strain. One
      strain with high-level resistance against tetracyclines carried the tet(M) gene.
      Sixty-three percent of the strains showed low-level resistance to lincomycin. The
      lnu(A) and lnu(B) genes were each only found in one strain. Compared with a
      similar investigation carried out in 1980, an increase was seen in resistance
      percentages with lincomycin (63% against 49%) and a slight decrease with
      tetracycline (66% against 74%).

PMID- 14681060
TI  - E-cadherin binding modulates EGF receptor activation.
AB  - We found that E-cadherin and epidermal growth factor receptor (EGFR) are
      associated in mammary epithelial cells and that E-cadherin engagement in these
      cells induces transient activation of EGFR, as previously seen in keratinocytes
      (37). In contrast, EGFR does not associate with and is not activated by N
      cadherin. Analysis of cells expressing chimeric cadherins revealed that the
      extracellular domain of E-cadherin is required for interaction with and
      activation of EGFR. This activation results in tyrosine phosphorylation of known
      EGFR substrates and reduction in focal adhesions. These interactions, however,
      are not necessary for suppression of cell motility by E-cadherin.

PMID- 14681062
TI  - Nutritional secondary hyperparathyroidism and osteodystrophia fibrosa in a
      Hodgson's hawk-eagle (Spizaetus nipalensis).
AB  - A Hodgson's hawk-eagle (Spizaetus nipalensis) reared by a falconer showed severe
      weakness with multiple fractures of bone. It had a history of being fed an all
      meat diet. Serological examination revealed a hypocalcaemia (72.0 microg/ml), and
      hypophosphataemia (29.0 microg/ml). Gross and microscopic examinations
      demonstrated severe osteodystrophia fibrosa (fibrous osteodystrophy)
      characterized by osteoclastic bone resorption and intertrabecular fibrosis with
      unmineralized trabecular bone containing a large amount of unmineralized osteoid.
      There was also hypertrophy and hyperplasia of the parathyroid glands, which is
      consistent with nutritional secondary hyperparathyroidism.

PMID- 14681063
TI  - Occurrence of avian leukosis virus subgroup J in commercial layer flocks in
      China.
AB  - Mortality from myeloid leukosis was observed in commercial layers from 12 farms
      in northern China. Affected chickens were extremely thin and dehydrated, bleeding
      occurred in feather follicles and claws, combs were pale and anaemic, phalanges
      were swollen, and many yellowish-white tumours were seen on the visceral surface
      of the sternum. Focal tumour cells, with spherical eosinophilic granules in the
      cytoplasm, were found in the liver, spleen, kidney, ovary, oviduct, lung, bone
      marrow, proventriculus and gut by histopathological examination.
      Immunohistochemical studies with a monoclonal antibody to gp85 of avian leukosis
      virus subgroup J (ALV-J) revealed antigen in all organs examined. Polymerase
      chain reaction tests using a pair of ALV-J-specific primers H5/H7 (Smith et al.,
      1998) produced a 545 basepair fragment. The sequence of the Polymerase chain
      reaction product was compared with that of the ALV-J HPRS-103 prototype strain.
      The identity of nucleotides and predicted amino acids was 97.4% and 96.1%,
      respectively. On this basis the disease in the egg-type chickens was diagnosed as
      an ALV-J infection. This is the first report of field cases of myeloid leukosis
      caused by ALV-J in commercial egg-type chickens.

PMID- 14681064
TI  - Fatal necrotic enteritis associated with Clostridium perfringens in wild crows
      (Corvus macrorhynchos).
AB  - Sporadic outbreaks of fatal enteritis occurred among free-living wild crows
      ('large billed' or 'wok' crow; Corvus macrorhynchos) in an open-air park in Japan
      in 2002. Eight crows were found dead during February, followed by two more in
      September, and five of the eight were examined histopathologically. At necropsy,
      all cases showed a markedly dilated small intestine, especially the jejunum and
      ileum, with large amounts of gas, and dark red to greenish-brown soft content.
      The necrotic intestinal wall was markedly thickened with multifocal haemorrhages.
      All cases had multifocal white foci in the liver, and four cases showed marked
      splenomegaly. Histologically, there was severe necrotic enteritis characterized
      by extensive mucosal necrosis and multifocal haemorrhages, as well as
      inflammatory cell infiltrations. A prominent pseudo-membrane formation was noted
      in the affected intestine. Severe adhesive peritonitis was also observed in three
      cases. Gram-positive bacilli were present in large numbers in the lumen, and in
      and around necrotic lesions in the affected intestine. The bacilli were positive
      for Clostridium perfringens enterotoxin type A by immunohistochemistry, and were
      also positive for C. perfringens type A using the immunofluorescence method. C.
      perfringens was isolated by anaerobic culture from the intestinal contents. The
      present enteritis was thought to be induced by proliferated C. perfringens in the
      intestine, and to be the cause of death.

PMID- 14681065
TI  - Temporal dynamics of the cellular, humoral and cytokine responses in chickens
      during primary and secondary infection with Salmonella enterica serovar
      Typhimurium.
AB  - Salmonella enterica serovar Typhimurium (S. Typhimurium) infections cause
      systemic disease in the young chick, whereas in the older chicken the infection
      is mainly restricted to the intestine. Chickens infected orally with S.
      Typhimurium (F98) at 6 weeks of age and re-infected 10 weeks later were monitored
      for antibody production, T-cell proliferation and production of selected
      cytokines (interferon-gamma, interleukin-1beta and transforming growth factor
      beta(4)). A strong coordinated antigen-specific humoral and cellular immune
      response was temporally linked to resolution of the primary infection. Enhanced
      levels of mRNA encoding the cytokines, interleukin-1beta, transforming growth
      factor-beta(4) and interferon-gamma were also evident during early phases of
      primary infection. Secondary infection was restricted to the intestine and of
      shorter duration than primary infection. Splenic immune responses were not
      further enhanced by secondary infection; indeed, antigen-specific proliferation
      was significantly reduced at 1 day after secondary infection, which may be
      interpreted as the trafficking of reactive T cells from the spleen to the gut.

PMID- 14681066
TI  - Avian metapneumovirus excretion in vaccinated and non-vaccinated specified
      pathogen free laying chickens.
AB  - Vaccinated and non-vaccinated specified pathogen-free White Leghorn laying
      chickens were challenged at peak of lay by the intravenous or oculonasal route
      with a virulent avian metapneumovirus (aMPV) subtype B chicken strain. Severe
      clinical signs and a drop in egg production were induced in the non-vaccinated
      intravenously challenged birds whereas the vaccinates were not affected. Live
      virus excretion was demonstrated in the faeces and respiratory tract of non
      vaccinated hens for up to 7 days post intravenous challenge. After oculonasal
      challenge, virus excretion could only be demonstrated in the respiratory tract
      for up to 5 days. No live virus excretion was found in either the faeces or the
      respiratory tract of vaccinated birds. Concurrent with live virus isolation, the
      presence of viral RNA was demonstrated by single reverse transcription-polymerase
      chain reaction (RT-PCR). Nested RT-PCR was more sensitive and viral RNA could be
      detected in non-vaccinated birds up to 28 days post either intravenous or
      oculonasal challenge, at which time the experiment was terminated. Viral RNA was
      detected for up to 12 days in vaccinated birds. This is the first study
      investigating excretion of aMPV and viral RNA in vaccinated and non-vaccinated
      laying hens challenged under experimental conditions. The results are of
      importance with regard to the persistence of aMPV and the appropriate diagnostic
      detection method in laying birds.

PMID- 14681067
TI  - Nucleotide sequence analysis of a C1 gene fragment of psittacine beak and feather
      disease virus amplified by real-time polymerase chain reaction indicates a
      possible existence of genotypes.
AB  - To investigate sequence diversity of psittacine beak and feather disease virus,
      samples collected from 31 psittacine species with or without clinical signs were
      tested for the presence of the viral genome. A real-time polymerase chain
      reaction was developed amplifying a 202 base pair fragment of the region encoding
      the capsid protein C1 and detecting 100 to 1000 genome equivalents. The
      nucleotide sequences of the polymerase chain reaction products showed 84.1 to
      100% identity with no consistent pattern with regard to the infected bird
      species. Amino acid exchanges were concentrated mainly in five of the 42 deduced
      positions. Sequences obtained from an outbreak of acute beak and feather disease
      in lories clustered in a separate branch of a phylogenetic tree. Sequences in
      samples from African grey parrots with feather disorders grouped together,
      whereas those from the same species with immunosuppression clustered in other
      branches. These results indicate the possible existence of beak and feather
      disease virus genotypes.

PMID- 14681068
TI  - Diagnosis of goose circovirus infection in Hungarian geese samples using
      polymerase chain reaction and dot blot hybridization tests.
AB  - A polymerase chain reaction (PCR) and dot blot hybridization (DBH) test have been
      developed for the diagnosis of infection by a novel circovirus of geese (GoCV).
      These tests were applied to samples of bursae of Fabricius from sick and dead
      birds from commercial goose farms in Hungary. In this second report of the
      occurrence of circovirus infection in diseased geese, 103 of 214 (48.1%) and 37
      of 150 (24.6%) birds, and 49 of 76 (64.5%) and 18 of 76 (23.7%) flocks were
      positive by PCR and DBH respectively. The sensitivity of the PCR test was such
      that 0.10 fg of virus DNA was detectable. The DBH test was less sensitive, only
      detecting larger amounts (40 pg) of DNA, but was used as a semi-quantitative
      method for detecting the presence of virus. The incidence of infection was
      affected by factors such as the age of the birds and rearing methods.

PMID- 14681069
TI  - Biocharacteristics shared by highly protective vaccines against Marek's disease.
AB  - Attenuated serotype 1 Marek's disease virus strains vary widely in their
      protection properties. This study was conducted to elucidate which
      biocharacteristics of serotype 1 MDV strains are related with protection. Three
      pairs of vaccines, each one including a higher protective (HP) vaccine and a
      lower protective (LP) vaccine originating from the same MDV strain, were studied.
      Two other highly protective vaccines (RM1 and CVI988/BP5) were also included in
      the study. Comparison within pairs of vaccines showed that marked differences
      existed between the HP and the LP vaccines. Compared with LP vaccines, HP
      vaccines replicated better in vivo. Also, they induced a significant expansion of
      total T cells and of the helper and cytotoxic T cell lineages (CD45(+)CD3(+),
      CD4(+)CD8(-), CD4(-)CD8(+)) as well as a marked increase in the expression of the
      antigens of MhcI and MhcII on T cells. Thus, our results show that in vivo
      replication and early stimulation of the T-cell lineage are two characteristics
      shared by HP vaccines. However, comparison among the four HP vaccines that
      provided protection equal to that of CVI988 (RM1, CVI988/BP5, CVI988 and 648A80)
      revealed variability, especially regarding in vivo replication. Strains RM1 and
      CVI988/BP5 showed much stronger replication in vivo than the other two vaccine
      strains (CVI988 and 648A80). Thus, no single set of characteristics could be used
      to identify the most protective Marek's disease vaccines, implying, perhaps, that
      multiple mechanisms may be involved.

PMID- 14681071
TI  - Proventricular adenocarcinoma in a Humboldt penguin (Spheniscus humboldti) and a
      great horned owl (Bubo virginianus); identification of origin by mucin
      histochemistry.
AB  - Cases of proventricular neoplasm in a Humboldt penguin (Spheniscus humboldti) and
      a great horned owl (Bubo virginianus) were observed. Microscopically, the
      neoplastic cells formed branching tubules or acini in both cases. Galactose
      oxidase-Schiff (GOS) staining revealed that the cytoplasm of the normal surface
      epithelium and surface mucosubstances of the proventriculus adjacent to the
      neoplasm were positive in both cases. The neoplastic cells in both cases were
      also classified as GOS-positive. Therefore, the two proventricular neoplasms in
      this report were diagnosed as proventricular adenocarcinoma that arose from the
      proventricular surface epithelium. This study suggests that the mucosubstances,
      which the neoplastic cells produced, were a useful index for identifying the
      origin of the neoplastic cells in the birds.

PMID- 14681070
TI  - Borrelia burgdorferi sensu lato infection in passerine birds from the Mazurian
      Lake region (Northeastern Poland).
AB  - The aim of the present study was to evaluate a potential role of different
      passerine birds species in Mazurian Lake region (northeast Poland) in the spread
      of Borrelia burgdorferi sensu lato, the spirochaete that causes Lyme disease. A
      total number of 1254 birds (representing 42 species) were captured during the 3
      year study period. Blood samples were collected from birds and analyzed with a
      nested polymerase chain reaction technique in order to detect fragments of the
      pathogen DNA. Positive results were obtained in 4.2% of all blood samples.
      Specifically, B. burgdorferi s.l. were detected in tree pipit (Anthus Erivialis;
      21.1% of 19 birds), dunnock (Prunella modularis; 15.8% of 19 birds), chaffinch
      (Fringilla coelebs; 12.7% of 166 birds), song thrush (Turdus philometos; 9.3% of
      54 birds), nuthatch (Sitta euopea; 7.7% of 26 birds), hawfinch (Coccothraustes
      coccothroustes; 6.7% of 15 birds), robin (Erithacus rebecula; 5.1% of 256 birds),
      blackbird (Turdus merula; 4.2% of 71 birds) and wren (Troglodytes troglodytes;
      3.7% of 27 birds). Additionally, the incidence of the infection was analyzed in
      relation to the habitat in which the birds resided (mixed coniferous forest or
      alder swamp forest), months of the study (from April to October), age and sex,
      but the differences were not statistically significant.

PMID- 14681072
TI  - Maternal vaccination against subclinical necrotic enteritis in broilers.
AB  - The inclusion of antibacterial feed additives has until now been the major
      strategy for controlling Clostridium perfringens-associated necrotic enteritis in
      broilers. In the present study, the effect of maternal immunization against the
      disease was examined. Broiler breeder hens were injected intramuscularly with
      candidate vaccines based on C. perfringens type A and type C toxoids adjuvanted
      with aluminium hydroxide. Vaccination resulted in a strong serum immunoglobulin G
      response to C. perfringens alpha-toxin in parent hens, and specific antibodies
      were transferred to their progeny. Subclinical necrotic enteritis in broilers was
      induced under field conditions or in a disease model, and the occurrence of
      specific enteric and hepatic lesions was evaluated in randomly selected birds. In
      three experiments, estimates of odds ratio for developing such lesions were 0.23,
      0.33 and 0.56 in maternally toxoid C-immunized broilers compared with non
      immunized controls. In toxoid A-immunized birds, odds ratios were estimated at
      0.41, 0.61 and 0.63. From these results, immunoprophylaxis seems to be an
      interesting alternative for the control of necrotic enteritis in broilers.

PMID- 14681073
TI  - Evaluation of an egg yolk enzyme-linked immunosorbent assay antibody test and its
      use to assess the prevalence of Mycoplasma synoviae in UK laying hens.
AB  - The frequency of Mycoplasma synoviae exposure in a convenience sample of
      commercial layers was established by the presence of antibody in eggs. Chloroform
      extracted egg yolks were found to be more suitable than saline-extracted yolks,
      and were used with a commercial enzyme-linked immunosorbent assay kit, having
      first established the sensitivity and specificity of the kit with eggs from known
      M. synoviae-positive and M. synoviae-negative flocks. For the prevalence study,
      pooled yolks from 12 eggs were obtained from each of 56 randomly selected laying
      farms in possession of a packing station number in the east of England. This
      number allowed 95% confidence of detection of antibody in one egg if present in
      50% of the flock. Eggs were taken from the oldest flock on each site and were
      returned with a completed questionnaire. The prevalence of egg antibody to M.
      synoviae was 78.6% (95% confidence interval, 65.6, 88.4). This study has
      confirmed that chloroform extraction of yolk antibody is a suitable approach for
      assessing the flock prevalence of M. synoviae infection in layer hens.

PMID- 14681075
TI  - Issues that must be addressed for risk assessment of mixed exposures: the U.S.
      EPA experience with air quality.
AB  - Humans are routinely exposed to a complex mixture of air pollutants in both their
      outdoor and indoor environments. The wide diversity of these exposure scenarios
      and potential for regional transport present the health scientist with a
      challenge of how to appropriately address complex air pollution mixtures.
      Similarly, regulators are faced with mixture issues ranging from exposures, to
      health outcomes, and to associated uncertainties that are in need of more
      definitive and strategic information to support informed decisions. This article
      provides a perspective of an empiricist on the background related to the issue of
      air pollution mixtures. Historic and current regulatory platforms for dealing
      with mixtures are described. Using the topic of particulate air pollution,
      general guidance through the nuances of potential interactions among PM
      constituents is provided, along with alterative approaches and examples, and how
      these support scientific and regulatory agendas. The impact of new cell and
      molecular technologies is inevitable, and we must be prepared to take advantage
      of these and other cross-cutting methods as they become available. Such
      innovative approaches hold the secret to high-throughput biologic dissection of
      component interactions and mixture profiles, which will aid in the assessment of
      risk.

PMID- 14681076
TI  - Metalworking fluid--the toxicity of a complex mixture.
AB  - Various chemicals are used in the manufacture of cooling and lubricating fluids
      and fall into the classes of straight, soluble, semisynthetic, and synthetic
      metalworking fluids. The diversity of chemicals and in-use contaminants makes the
      risk assessment of metalworking fluids quite difficult. Toxicologists have used a
      number of methods to evaluate the component(s) responsible for the adverse
      pulmonary effects of metal working fluid aerosols encountered in the workplace.
      Although investigators have studied the adverse effects of metalworking fluid
      chemicals alone and in combination, the majority of evidence strongly suggests
      that the microbial changes that occur in fluid composition, during use and
      storage in the workplace, are responsible for the pulmonary effects reported for
      workers exposed to metalworking fluid aerosols. This review discusses the
      methodologies used to examine the toxicity of the complex nature of modern
      metalworking fluids and the findings that point toward bacterial endotoxin as a
      major contributor to their adverse effects.

PMID- 14681077
TI  - Effect of diesel exhaust particulate (DEP) on immune responses: contributions of
      particulate versus organic soluble components.
AB  - The effect of diesel exhaust particulate (DEP) exposure on innate, cellular and
      humoral pulmonary immunity was studied using high-dose, acute-exposure rat,
      mouse, and cell culture models. DEP consists of a complex mixture of
      petrochemical-derived organics adsorbed onto elemental carbon particles. DEP is a
      major component of particulate urban air pollution and a health concern in both
      urban and occupational environments. The alveolar macrophage is considered a key
      cellular component in pulmonary innate immunity. DEP and DEP organic extracts
      have been found to suppress alveolar macrophage function as demonstrated by
      reduced production of cytokines (interleukin-1 [IL-1], tumor necrosis factor-
      alpha [TNF- alpha]) and reactive oxygen species (ROS) in response to a variety of
      agents, including lipopolysaccharide (LPS), interferon- gamma (IFN- gamma), and
      bacteria. Fractionation of DEP organic extract suggests that this activity was
      predominately in polyaromatic-containing and more polar (resin) fractions.
      Organic-stripped DEP did not alter these innate pulmonary immune responses. DEP
      also depressed pulmonary clearance of Listeria monocytogenes and Bacillus
      Calmette-Guerin (BCG). The contribution of the organic component of DEP is less
      well defined with respect to acquired and humoral immunity. Indeed, both DEP and
      carbon black enhanced humoral immune responses (specific immunoglobulin [Ig] E
      and IgG) in an ovalbumin-sensitized rat model. It is concluded that both the
      particulate and adsorbed organics may contribute to DEP-mediated immune
      alterations.

PMID- 14681078
TI  - Pulmonary responses to welding fumes: role of metal constituents.
AB  - It is estimated that more than 1 million workers worldwide perform some type of
      welding as part of their work duties. Epidemiology studies have shown that a
      large number of welders experience some type of respiratory illness. Respiratory
      effects seen in full-time welders have included bronchitis, siderosis, asthma,
      and a possible increase in the incidence of lung cancer. Pulmonary infections are
      increased in terms of severity, duration, and frequency among welders. Inhalation
      exposure to welding fumes may vary due to differences in the materials used and
      methods employed. The chemical properties of welding fumes can be quite complex.
      Most welding materials are alloy mixtures of metals characterized by different
      steels that may contain iron, manganese, chromium, and nickel. Animal studies
      have indicated that the presence and combination of different metal constituents
      is an important determinant in the potential pneumotoxic responses associated
      with welding fumes. Animal models have demonstrated that stainless steel (SS)
      welding fumes, which contain significant levels of nickel and chromium, induce
      more lung injury and inflammation, and are retained in the lungs longer than mild
      steel (MS) welding fumes, which contain mostly iron. In addition, SS fumes
      generated from welding processes using fluxes to protect the resulting weld
      contain elevated levels of soluble metals, which may affect respiratory health.
      Recent animal studies have indicated that the lung injury and inflammation
      induced by SS welding fumes that contain water-soluble metals are dependent on
      both the soluble and insoluble fractions of the fume. This article reviews the
      role that metals play in the pulmonary effects associated with welding fume
      exposure in workers and laboratory animals.

PMID- 14681079
TI  - Soluble metals associated with residual oil fly ash increase morbidity and lung
      injury after bacterial infection in rats.
AB  - Inhalation of residual oil fly ash (ROFA) has been shown to impair lung defense
      mechanisms in laboratory animals and susceptible populations. Bioavailability of
      soluble transition metals has been shown to play a key role in lung injury caused
      by ROFA exposure. The goal of this study was to evaluate the effect of soluble
      metals on lung defense and injury in animals preexposed to ROFA followed by
      pulmonary challenge with a bacterial pathogen. ROFA was suspended in saline (ROFA
      TOTAL), incubated overnight at 37 degrees C, and separated by centrifugation into
      soluble (ROFA-SOL) and insoluble (ROFA-INSOL) fractions. A portion of the soluble
      sample was treated with the metal-binding resin Chelex for 24 h at 37 degrees C.
      Sprague-Dawley rats were intratracheally dosed at d 0 with ROFA-TOTAL (1.0 mg/100
      g body weight), ROFA-INSOL, ROFA-SOL, saline, saline + Chelex, or ROFA-SOL +
      Chelex. At d 3, 5 x 10(5) Listeria monocytogenes were intratracheally instilled
      into rats from each treatment group. At d 6, 8, and 10, left lungs were removed,
      homogenized, and cultured to assess bacterial clearance. Histopathological
      analysis was performed on the right lungs. Pulmonary exposure of ROFA-TOTAL or
      ROFA-SOL before infection led to a marked increase in lung injury and
      inflammation at all three time points after inoculation, and an increase in
      morbidity in comparison to saline control rats. Treatment with ROFA-INSOL, saline
      + Chelex, or ROFA-SOL + Chelex caused no significant increases in lung damage and
      morbidity when compared to control. By d 10, the ROFA-SOL and ROFA-TOTAL groups
      had approximately 200-fold more bacteria in the lung than saline control,
      indicating the inability of these groups to effectively respond to the infection.
      None of the other treatment groups had significant impairments in bacterial
      clearance when compared to saline. In conclusion, exposure to ROFA-TOTAL and ROFA
      SOL significantly suppressed the lung response to infection. These results
      suggest that soluble metals present in ROFA may play a key role in increased
      susceptibility to pulmonary infection in exposed populations.

PMID- 14681080
TI  - Toxicological characteristics of endocrine-disrupting chemicals: developmental
      toxicity, carcinogenicity, and mutagenicity.
AB  - It is generally accepted that endocrine-disrupting chemicals (EDCs) play a role
      in a variety of adverse health effects in an intact organism or its progeny as a
      consequence of changes in the endocrine system. Primary toxic effects of EDCs
      were reported to be related to infertility, reduction in sperm count, and
      teratogenicity, but other important toxic effects of EDCs such as carcinogenicity
      and mutagenicity have also been demonstrated. The aim of the present study was to
      systematically analyze the toxicological characteristics of EDCs in pesticides,
      industrial chemicals, and metals. A comprehensive literature survey on the 48
      EDCs classified by the Centers for Disease Control and Prevention (CDC) was
      conducted using a number of databases which included Medline, Toxline, and
      Toxnet. The survey results revealed that toxicological characteristics of EDCs
      were shown to produce developmental toxicity (81%), carcinogenicity (79%, when
      positive in at least one animal species; 48%, when classified based on IARC
      evaluation), mutagenicity (79%), immunotoxicity (52%), and neurotoxicity (50%).
      Regarding the hormone-modulating effects of the 48 EDCs, estrogenic effects were
      the most predominant in pesticides, while effects on thyroid hormone were found
      for heavy metals. EDCs showing estrogen-modulating effects were closely related
      to carcinogenicity or mutagenicity with a high degree of sensitivity. Systematic
      information on the toxicological characteristics of the EDCs will be useful for
      future research directions on EDCs, the development of new screening methods,
      legal regulation, and for investigations of their mechanism of action.

PMID- 14681081
TI  - Environmental and occupational health hazards associated with the presence of
      asbestos in brake linings and pads (1900 to present): a "state-of-the-art"
      review.
AB  - Throughout the history of automobile development, chrysotile asbestos has been an
      essential component of vehicle brake linings and pads. Acceptable alternatives
      were not fully developed until the 1980s, and these were installed in vehicles
      produced over the past decade. This article presents a "state-of-the-art"
      analysis of what was known over time about the potential environmental and
      occupational health hazards associated with the presence of chrysotile asbestos
      in brake linings and pads. As part of this analysis, the evolution of automobile
      brakes and brake friction materials, beginning with the early 1900s, is
      described. Initial concerns regarding exposures to asbestos among workers
      involved in the manufacture of friction products were raised as early as 1930.
      Between 1930 and 1959, eight studies were conducted for which friction product
      manufacturing workers were part of the population assessed. These studies
      provided evidence of asbestosis among highly exposed workers, but provided little
      information on the magnitude of exposure. The U.S. Public Health Service proposed
      the first occupational guideline for asbestos exposure in 1938. The causal
      relationship between asbestos exposure and lung cancer was confirmed in 1955 in
      asbestos textile workers in the United Kingdom, and later, in 1960, in South
      Africa, mesothelioma was attributed to asbestos exposure to even relatively low
      airborne concentrations of crocidolite. Between 1960 and 1974, five epidemiology
      studies of friction product manufacturing workers were conducted. During this
      same time period, the initial studies of brake lining wear (dust or debris)
      emissions were conducted showing that automobile braking was not a substantial
      contributor of asbestos fibers greater than 5 microm in length to ambient air.
      The first exposure surveys, as well as preliminary health effects studies, for
      brake mechanics were also conducted during this period. In 1971, the Occupational
      Safety and Health Administration promulgated the first national standards for
      workplace exposure to asbestos. During the post-1974 time period, most of the
      information on exposure of brake mechanics to airborne asbestos during brake
      repair was gathered, primarily from a series of sampling surveys conducted by the
      National Institute of Occupational Safety and Health in the United States. These
      surveys indicated that the time-weighted average asbestos

PMID- 14681082
TI  - Equilibrium and balanced growth of a vegetative crop.
AB  - MODEL: A previously developed dynamic model, NICOLET, designed to predict growth
      and nitrate content of a lettuce crop, is subjected to (virtual) constant
      environmental conditions. For every combination of shoot and root environment,
      the cell sap, here assumed to reside in the "vacuole" compartment, equilibrates
      at a certain nitrate concentration level. This, in turn, defines the composition
      of the crop in terms of carbon and nitrogen content in each of the three
      compartments of the model. Growth under constant environmental conditions is
      defined as "equilibrium" growth (EG). If, in addition, the source strengths of
      carbon and nitrogen balance each other, as well as the sink strength of the
      growing crop, the growth is said to be "balanced" (BG). RESULTS: It is shown that
      the range of BG approximately coincides with the range of "mild" nitrogen stress,
      where reduction in nitrogen availability results in a mild reduction of relative
      growth rate (RGR). Beyond a certain low nitrate concentration in the cell sap,
      the N-stress becomes "severe" and the loss of growth increases considerably.
      CONCLUSIONS: The model is able to mimic the five central observations of many
      constant-environment growth-chamber experiments, namely (1) the initial
      exponential growth and later decline of the RGR, (2) the constant chemical
      composition, (3) the equality of the RGR and the relative nutrient supply rate
      (RNR), (4) the proportionality between the N : C ratio and the RNR, and (5) the
      proportionality between the water content and the reduced N content. Guidelines
      for the optimal combination of the shoot and root environments are suggested.

PMID- 14681083
TI  - Asian cardiovascular surgery: a new horizon.

PMID- 14681084
TI  - Fate of polytetrafluoroethylene monocusp pulmonary valves in an animal model.
AB  - Creation of a competent pulmonary monocusp valve facilitates transition from
      pressure to volume overload following right ventricular outflow tract
      reconstruction. To determine intermediate-term results and performance of the
      different types of polytetrafluoroethylene membrane used to construct monocusp
      valves and transannular patches, 12 infant lambs underwent excision of the native
      pulmonary valve and insertion of a monocusp valve and transannular patch made
      from one of 4 types of membrane. Echocardiography was performed after 3, 6, 9,
      and 12 months, and cardiac catheterization was carried out prior to animal
      sacrifice at 6 (n = 4) or 12 (n = 8) months. There was no postoperative morbidity
      or mortality. On echocardiography, 6 valves were mobile (50%), 4 had diminished
      mobility (33%), and 2 were fixed (17%) prior to sacrifice. At catheterization,
      mild, moderate, and severe pulmonary regurgitation was observed in 4 valves each
      (33%), with no stenosis. Right ventricular outflow tract reconstruction with
      polytetrafluoroethylene monocusp valves can be safely accomplished with good
      early competence, variable degrees of late insufficiency, and no stenosis.
      Compared to an open microstructure, the closed polytetrafluoroethylene
      microstructure showed a milder fibroinflammatory reaction and fewer foci of
      microcalcification, with sparing of the free edge of the monocusp; this
      correlated with better intermediate-term hemodynamic performance.

PMID- 14681085
TI  - Off-pump surgery: a choice in unstable angina.
AB  - The benefit and safety of off-pump coronary artery bypass surgery in patients
      with unstable angina was assessed retrospectively. From February 1996 to October
      2001, 5,306 patients underwent multivessel off-pump coronary artery bypass, of
      whom 920 (17%) had unstable angina. In these 920 patients, ejection fractions
      ranged from 15% to 70%, 203 (22%) had an ejection fraction of 20%-35%, and 11
      (1%) had an ejection fraction < 20%. Triple-vessel disease was present in 625
      patients. Preoperative intraaortic balloon pump support was used in 28 patients.
      Operative approaches included mid sternotomy (86%), lower partial sternotomy
      (9%), and left anterior thoracotomy (2%). The number of grafts ranged from 1 to 5
      with a mean of 2.43 +/- 0.86, and 92.3% of patients received a left internal
      mammary artery graft. Twenty-two patients need intraoperative intraaortic balloon
      pumping. Ten patients (1%) suffered perioperative myocardial infarction. The mean
      hospital stay was 7.8 +/- 4.3 days. Hospital mortality was 2/920 (0.22%).
      Intraaortic balloon pumping was helpful in these cases of unstable angina
      refractory to medical therapy. Off-pump coronary artery surgery was found to be
      safe and beneficial in these patients.

PMID- 14681086
TI  - Ultrasonography and lung mechanics can diagnose diaphragmatic paralysis quickly.
AB  - Diaphragmatic paralysis after cardiovascular surgery requires early diagnosis
      prior to extubation. The effectiveness of ultrasonography and a lung mechanics
      assessment was evaluated. Paralysis of the diaphragm was diagnosed when the
      diaphragm failed to move or moved in a cephalad direction during inspiration. It
      was diagnosed in 3 of 40 patients (7.5%) who underwent cardiovascular surgery
      from 1998 to 1999. Patients were extubated when all parameters met the extubation
      criteria, irrespective of the presence or absence of diaphragmatic paralysis. One
      patient required prolonged assisted ventilation and died from mediastinitis on
      the 35th postoperative day. The other 2 patients required assisted ventilation
      for an additional 1-3 days. Ultrasonography and a lung mechanics assessment are
      effective tools for the early diagnosis of diaphragmatic paralysis and assessment
      of respiratory function after cardiovascular surgery.

PMID- 14681087
TI  - Why are the results of coronary artery bypass grafting in women worse?
AB  - A study was conducted to assess the early results of isolated coronary artery
      bypass grafting in women and to determine the risk factors for early
      postoperative complications. Between January 1994 and July 2001, 1,730 patients
      (301 women and 1,429 men) underwent isolated myocardial revascularization.
      Conventional bypass procedure was performed on 1,554 patients (270 female and
      1,284 male) and off-pump procedure on 176 patients (31 female and 145 male).
      Hospital mortality was significantly higher in women than in men (5.6% versus
      2.9%). Low cardiac output syndrome developed in 8.6% of women and 8.5% of men.
      Postoperative myocardial infarction occurred in 5.3% of women and 4.3% of men (p
      < 0.05). The rate of infectious complications was significantly higher in women
      (7.0%) than in men (5.8%). The independent risk factors for early mortality in
      women were left ventricular ejection fraction below 40%, left main disease, and
      urgent operation. The need for urgent surgery in women was also found to be a
      significant independent predictor of low cardiac output syndrome and
      postoperative myocardial infarction. In conclusion, higher hospital mortality and
      morbidity in women undergoing coronary surgery are partially related to the
      severity of coronary atherosclerosis and comorbid conditions.

PMID- 14681088
TI  - Thymectomy for myasthenia gravis: 12-year experience.
AB  - Thymectomy has been shown to be effective in the treatment of myasthenia gravis.
      The logical goal of operation is the complete removal of the thymus, but there is
      no consensus on the selection criteria of patients for surgery and the choice of
      surgical approach. We retrospectively reviewed 56 patients with myasthenia gravis
      who had been treated surgically by transsternal radical thymectomy between
      January 1990 and March 2002. The patients were symptomatically grouped according
      to the modified Osserman clinical classification. There was 1 hospital death, and
      53 patients had been followed up for between 1 month and 12 years. Improvement
      after thymectomy was observed in 1 of 4 patients (25%) in Osserman group I, 25 of
      34 patients (74%) in Osserman group IIA, and 16 of 18 patients (89%) in combined
      Osserman groups IIB and IIC. Transsternal radical thymectomy is an effective
      therapy for myasthenia gravis. Sustained improvement is achievable in female
      patients with moderate to severe symptoms and in patients with thymic
      hyperplasia.

PMID- 14681089
TI  - Beneficial effect of aspirin on renal function post-cardiopulmonary bypass.
AB  - Urine thromboxane, plasma creatinine, and creatinine clearance were determined
      perioperatively in 20 patients undergoing coronary bypass surgery. Ten patients
      took aspirin until the day of surgery, and 10 discontinued aspirin at least one
      week before surgery. A significant increase in urine thromboxane following
      establishment of cardiopulmonary bypass was observed only in the control group.
      Plasma creatinine increased in the control group on the 1st postoperative day
      (from 81.9 +/- 13.2 to 97.6 +/- 13.2 micromol.L(-1), p = 0.02) and decreased next
      day to the preoperative level (82.7 +/- 9 micromol.L(-1), p = 0.03). In the
      aspirin group, creatinine remained unchanged on the 1st postoperative day (89.4
      +/- 14.2 vs. 87.2 +/- 7.7 micromol.L(-1), p = 0.6), and increased significantly
      on the 2nd day (101.4 +/- 8.5 micromol.L(-1), p = 0.01). The aspirin group had
      higher creatinine levels (p < 0.0001) and lower creatinine clearance (60.2 +/-
      16.5 vs. 82 +/- 25.7 mL.min(-1), p < 0.0001) than the control group on the 2nd
      postoperative day. A significant positive correlation was seen between urine
      thromboxane and creatinine on day 2 in both groups (r = 0.6). Aspirin
      administrated before coronary surgery may have a beneficial effect on renal
      function, probably mediated by its antiplatelet activity and thromboxane
      inhibition.

PMID- 14681090
TI  - Thrombectomy with disc rotation of medtronic valves.
AB  - Thrombotic obstruction of prosthetic valves is a serious problem. Early diagnosis
      and prompt treatment are life-saving in these cases. Three patients presented
      with subacute and chronic symptoms of prosthetic valve thrombosis of varying
      duration (7 days to 2 years). All 3 had a Medtronic Hall tilting disc valve
      implanted in a previous operation in the aortic or mitral position. Diagnosis was
      established by 2-dimensional echocardiography. Under cardiopulmonary or
      femorofemoral bypass, thrombectomy and rotation of the disc within the valve
      housing were performed through a median sternotomy. All the patients had an
      uncomplicated postoperative course. Pressure gradients fell markedly at discharge
      8 to 10 days after surgery. The patients were followed up for between 3 and 11
      months, during which they showed excellent prosthetic valve function and reduced
      gradients. The ability to rotate the valve within the housing allows adequate
      thrombectomy and pannus excision. Even several years after implantation (more
      than 10 years in 2 cases), the valve could still be rotated readily to obtain
      optimum flow and low pressure gradients.

PMID- 14681091
TI  - Polyurethane grafts: a viable alternative for dialysis arteriovenous access?
AB  - Polyurethane grafts, promoted for their self-sealing properties and low
      complication rates, were recently introduced for hemodialysis access. We review
      our experience with this graft material to determine its complication and patency
      rates. Between January 1995 and December 1999, 118 patients, 75 female and 43
      male, with a mean age of 51 years, had a total of 163 polyurethane arteriovenous
      grafts inserted. The grafts were mostly 6 mm in diameter (69.3%), placed in a
      loop configuration (91.4%) in the forearm (49.7%). The median follow-up period
      was 12 months. The grafts were first cannulated for hemodialysis at a median time
      of 19 days after implantation, with 12% used within 3 days. Thrombosis and
      infection were the most common complications at rates of 32.7% and 30.0%,
      respectively. Infection was the most common cause of graft loss (61.5%). These
      complications were amenable to salvage intervention. The 1-year primary and
      secondary patency rates were 73% and 86%, respectively; the 3-year secondary
      patency rate, 72%. The 1-year serviceability rate was 64%. With satisfactory
      patency rates and the advantage of its self-sealing properties permitting early
      cannulation, polyurethane grafts provide a viable alternative for hemodialysis
      access. Early recognition and appropriate management of complications can prolong
      graft survival.

PMID- 14681092
TI  - Combined aortic and mitral valve repair.
AB  - Six patients, median age 63.3 years (range, 54 to 68 years), underwent
      concomitant mitral and aortic valve repair from January 2000 to August 2001.
      Surgical reports and general clinical data were reviewed retrospectively. All
      patients had degenerative valvular disease, although one patient also had
      annuloaortic ectasia. There were no surgical complications. The 30 day survival
      rate was 100%, and the New York Heart Association classification score improved
      from 2.2 (range, 1 to 2) preoperative, to 1.0 (all patients) postoperatively (p =
      0.03) As measured by intraoperative transesophageal echocardiography, the left
      ventricular end-diastolic diameter decreased from 6.0 cm (range, 5.4 to 6.3 cm)
      to 4.7 cm (range, 4.0 to 5.2 cm) and the left ventricular end-systolic diameter
      decreased from 3.7 cm (range, 3.4 to 4.1cm) to 3.1 cm (range, 2.9 to 3.7 cm). No
      patient developed endocarditis, thromboembolism or hemorrhage. There was no valve
      related morbidity during a 1 year follow up. Double valve repair is an acceptable
      alternative to valve replacement in selected patients with some types of valvular
      disease. Longer term follow up with greater numbers of patients is needed.

PMID- 14681093
TI  - Predictors of outcome for myasthenia gravis after thymectomy.
AB  - The aim of this study was to assess the clinical outcome of patients with
      myasthenia gravis treated with maximal thymectomy and to identify prognostic
      variables that predict the outcome. Over 15 years, from 1986 to 2001, we
      collected data on 100 patients with myasthenia gravis who underwent maximal
      thymectomy and retrospectively reviewed their outcome. Women comprised 63% and
      the median age was 25 years (range, 4 to 61). The median duration of the disease
      was 26 months (range, 1 to 240). According to the Osserman classification, there
      were seven patients in class I, 31 in class II, 47 in class III, and 15 in class
      IV. In non thymomatous patients (93 patients), complete remission rate
      progressively increased from 37.4% to 58.2% and 75% at 3, 10 and 15 years of
      follow-up respectively. These findings suggest that the complete remission rate
      is prone to increase with time after maximal thymectomy. The total benefit rate
      achieved was estimated to be 86% while 14% did not improve at a mean follow-up
      period of 7.6 years (range, 8 to 180 months). Univariate analysis (p < 0.05)
      showed that age, thymic histology and ectopic thymic tissue are significant
      prognostic factors for outcome.

PMID- 14681094
TI  - Lung function after deep hypothermic cardiopulmonary bypass in infants.
AB  - There is increasing concern about neurologic injury due to deep hypothermia with
      low flow during repair of complex congenital heart defects in neonates and
      infants. Twenty infants with ventricular septal defect and pulmonary hypertension
      were randomly assigned to cardiac repair under deep hypothermia with circulatory
      arrest or deep hypothermia with low flow. Measurements of static pulmonary
      compliance, airway resistance, and respiratory index were performed before
      institution of cardiopulmonary bypass and at 5 minutes and 2 hours after
      cessation of cardiopulmonary bypass. Both groups had significant pulmonary
      dysfunction in terms of static pulmonary compliance, airway resistance, and
      respiratory index. There was greater impairment of pulmonary compliance and
      respiratory index after deep hypothermia with low flow, and this group required
      longer intensive care unit stay.

PMID- 14681095
TI  - Surgical repair of a distal arch aneurysm with a stent-graft.
AB  - This study evaluates the effectiveness and potential complications of stent
      grafting for the treatment of distal arch aneurysms using profound hypothermia
      and circulatory arrest with retrograde cerebral perfusion. Between December 1998
      and December 2001, 9 consecutive patients with a distal arch aneurysm (6 men and
      3 women, mean age 71 years) underwent surgical repair using a stent-graft.
      Profound hypothermic circulatory arrest and retrograde cerebral perfusion were
      performed in all patients. Endovascular leakage was screened postoperatively
      using three-dimensional computerized tomography. The mean follow-up period was
      27.4 months. Thirty day mortality was 0%. One patient died 3 months after stent
      grafting due to proximal leakage into her aneurysm. The mean postoperative
      extubation period was 2.1 days. No patients suffered cerebral infarction or
      paraplegia. Although preliminary outcomes using this technique were good,
      endovascular leakage is a concern. We suggest that, if major proximal leakage is
      recognized postoperatively, re-intervention should be performed as soon as
      possible. Endovascular stent-grafting appears to be a good alternative treatment
      for distal arch aneurysms, although longer follow-up is necessary to more
      comprehensively evaluate this procedure.

PMID- 14681096
TI  - Extensive aortic surgery in Marfan syndrome: 16-year experience.
AB  - The aim of this study was to evaluate the clinical outcome of surgical treatment
      in patients with Marfan syndrome. Between 1985 and November 2001, 33 patients
      with Marfan syndrome were operated for chronic aneurysm of the aortic root with
      involvement of the ascending aorta in 20 patients and type A dissection in 13
      patients. The patients comprised 24 males and 9 females with a mean age of 31.9
      +/- 9.7 years (range, 18 to 54 years). The mean diameter of the ascending aorta
      was 6.6 +/- 1.6 cm and that of the aortic root was 5.4 +/- 1.2 cm. Hemodynamic
      instability was observed in 11 patients. The aortic arch was replaced in 7
      patients. There was no hospital mortality. Late mortality was 6%, involving 2
      patients who had aortic valve replacement. Actuarial freedom from death was 92.3%
      +/- 7.4% at 12 years and from late aortic complications was 86.4% +/- 9.4% at 13
      years. Aortic aneurysm was a significant univariate adverse factor for late
      aortic complications. Aortic surgery can be performed in Marfan patients with low
      morbidity and mortality. Aggressive surgical intervention does not impair
      surgical outcome while it decreases reoperation risk.

PMID- 14681097
TI  - Total cavopulmonary connection in a bedridden patient with Sotos syndrome.
AB  - Sotos syndrome is an overgrowth disorder of unknown etiology associated with a
      high incidence of congenital heart defects. Of 60 patients with Sotos syndrome
      treated in our hospital, 6 had congenital heart defects. We describe a case of
      successful total cavopulmonary connection at 30 months of age in a patient having
      pulmonary atresia with intact ventricular septum and a patent ductus arteriosus
      who had walking disability. The postoperative course was uneventful.

PMID- 14681098
TI  - Esophagopleural fistula following spontaneous rupture of traction diverticulum.
AB  - A rare case of esophagopleural fistula following spontaneous rupture of a
      traction diverticulum of the esophagus in a 25-year-old man was successfully
      treated by diverticulectomy.

PMID- 14681099
TI  - Repair of tuberculous aneurysm of distal aortic arch.
AB  - A 65 year old female patient presented with one episode of massive haemoptysis
      requiring transfusion and subsequently cough with streaky haemoptysis.
      Computerized tomographic scan and angiogram revealed aneurysm of the distal
      aortic arch. She underwent elective repair of the pseudoaneurysm through median
      sternotomy and the bronchial communication was closed through left thoracotomy.
      Tubercle bacilli were identified in the contents and excised wall of aortic
      tissue.

PMID- 14681100
TI  - Cardiac anomalies in Turner Syndrome.
AB  - This is the case of a 30-year-old woman with Turner Syndrome, with Mosaicism,
      exhibiting a bicuspid aortic valve with aortic stenosis, ascending aortic
      dilatation, pseudocoarctation of the aorta, left superior vena cava and lusoria
      subclavian artery. The successful surgical procedure consisted of the replacement
      of the aortic root and ascending aorta with a composite valved graft.

PMID- 14681101
TI  - Repair of ascending aortic aneurysm in a patient with fibrosarcoma over sternum.
AB  - The combination of an ascending aortic aneurysm and suprasternal soft tissue
      tumor is rarely reported in the literature. This case involves a 62-year-old man
      diagnosed with an ascending aortic aneurysm and a fibrosarcoma over the sternum
      that was successfully treated by surgery. The patient underwent an aortic
      replacement operation with a Dacron graft and a muscle flap transposition
      procedure to cover the defect over the sternum.

PMID- 14681102
TI  - Chylothorax following coronary bypass grafting: treatment by talc pleurodesis.
AB  - Chylothorax after myocardial revascularization is a rare but serious
      complication. There is as yet no definitive treatment. We report a case in which
      chylothorax was diagnosed on the 3rd postoperative day. Conservative management
      with dietary restriction to medium-chain triglyceride led to reduction of chyle
      leakage from 300 to 400 mL/day to 50 to 60 mL/day 3 days later. However, the leak
      persisted until talc pleurodesis was performed.

PMID- 14681103
TI  - Ascending aorta-abdominal aorta bypass for Takayasu's arteritis.
AB  - Three patients with type III Takayasu's arteritis were referred to us because of
      the upper extremity hypertension and vascular claudication of the lower
      extremities. They underwent extra-anatomic ascending aorta-abdominal aorta bypass
      with vascular graft under a median sternotomy and a splitted midline laparotomy
      incision without cardiopulmonary bypass. The postoperative course was uneventful.
      Upper extremity hypertension and vascular claudication were completely resolved.

PMID- 14681104
TI  - Endoscopic-assisted atraumatic coronary artery bypass.
AB  - Minimally invasive operations designed to graft the left anterior descending
      coronary artery with the left internal mammary artery are either traumatic to the
      chest wall or technically difficult and expensive. This report describes a novel
      procedure that is less traumatic and simpler.

PMID- 14681105
TI  - Suprahepatic approach for peritoneal dialysis in neonatal cardiac surgery.
AB  - For peritoneal dialysis of neonates after cardiac surgery under cardiopulmonary
      bypass, a Tenckhoff catheter was inserted via the sternotomy wound and guided
      suprahepatically into the abdomen. The technique was used in 84 neonates and
      found to be safe, simple, and reproducible.

PMID- 14681106
TI  - Pharmacotherapy of atrial fibrillation.
AB  - Atrial fibrillation is the most common sustained arrhythmia of clinical
      significance. Its prevalence rises with age. It is a significant cause of
      thromboembolic phenomena. We describe briefly the etiology and classification of
      atrial fibrillation, the risk factors for thromboembolism and stroke associated
      with it, the indications for hospitalization, and the therapeutic goal. We
      discuss in depth the management strategies for such patients and compare the
      impact of rate versus rhythm control in reducing morbidity and mortality
      attributed to arrhythmia, in light of past and present trials. A brief overview
      of the drugs used in the management of atrial fibrillation, their pharmacology
      and dosage, their effects and use in rhythm versus rate control with important
      side effects are also included. Finally, the prevention and treatment of
      thromboembolism in patients with atrial fibrillation, an important aspect of
      therapy, is revisited in light of recent advances.

PMID- 14681107
TI  - Tension enterothorax.

PMID- 14681108
TI  - Dysphagia lusorum.

PMID- 14681109
TI  - Unicuspid aortic valve.

PMID- 14681110
TI  - Bilateral longitudinal reinforcement of median sternotomy closure.

PMID- 14681112
TI  - Part I: Cerebral organization of music-related functions. Introduction.

PMID- 14681113
TI  - Music and the brain.
AB  - The aim of this paper is to illustrate how studying music from a neuroscience
      perspective may be a valuable way to probe a variety of complex cognitive
      functions and their neural substrate. Three different sets of issues are
      described. First, studies dealing with the brain correlates of musical imagery
      are discussed. This topic is of interest in that it illustrates how subjective
      sensations may be studied via objective techniques, and gives insight into neural
      systems associated with internal phenomena. Second, some findings pertaining to
      absolute pitch are presented. Absolute pitch is a useful example of a highly
      specific cognitive skill that is unevenly distributed in the population.
      Examination of its neural basis helps to understand aspects of memory function
      and points to ways to explore individual differences in brain organization that
      underlie differential skills. The final topic, music and emotion, has not been
      the subject of much systematic research, but it is of great interest because it
      intersects with a large literature on the neuroscience of affective processing.
      Findings from some studies indicate that music may engage systems concerned with
      biological reward, raising interesting but so far unanswered questions about the
      broader role of music in human experience.

PMID- 14681115
TI  - The promises of change-related brain potentials in cognitive neuroscience of
      music.
AB  - Even when simultaneously performing a task unrelated to sounds, the human
      auditory cortex can precisely model the invariances of the acoustic environment.
      Data acquired in a mismatch negativity (MMN) paradigm have shown that temporally
      and spectrally complex sounds as well as their relations are automatically
      represented in the human auditory cortex. Furthermore, MMN data indicate that
      these neural sound representations are spatially distinct from phonetic and
      musical sounds within and between the cerebral hemispheres. Most MMN studies were
      conducted in pitch dimension, but temporal aspects of sound processing are also
      under increasing experimentation. To some extent, musical expertise is also
      reflected in sound representation accuracy as indexed by the MMN paradigm.

PMID- 14681114
TI  - Toward the neural basis of processing structure in music. Comparative results of
      different neurophysiological investigation methods.
AB  - In major-minor tonal music, chord functions are arranged according to certain
      regularities. The dominant-tonic progression, known as an authentic cadence, is
      often used as a marker of the end of a harmonic progression and has been
      considered a basic syntactic structure of major-minor tonal music by several
      music theorists and music psychologists. We review data from studies in which
      brain responses to an authentic cadence were compared to those elicited by music
      syntactically inappropriate endings. In event-related electric brain potentials
      (recorded with EEG), the inappropriate endings elicit early right anterior
      negativity (ERAN), which is maximal around 200 ms after the presentation of an
      inappropriate chord. The ERAN is reminiscent of early anterior negativities
      elicited by syntactic incongruities during the perception of language.
      Magnetoencephalographic (MEG) data suggest that the ERAN is generated in the
      inferior frontolateral cortex, an area known to be crucially involved in the
      processing of (linguistic) syntax. Interestingly, the ERAN can be recorded in
      nonmusicians and in children, indicating that the ability to acquire (implicit)
      knowledge about musical regularities and to process musical information according
      to this knowledge is a general ability of the human brain. This ability is
      probably of great importance for the acquisition of language in infants and
      children.

PMID- 14681116
TI  - Functional imaging of pitch analysis.
AB  - This work addresses the brain basis for the analysis of pitch and pitch patterns
      required for normal musical perception. Recent functional imaging experiments are
      consistent with a hierarchical scheme for the analysis of pitch. Mechanisms in
      the ascending auditory pathway to the primary auditory cortex allow the
      representation of the spectral and temporal features of individual notes required
      for the perception of their pitch. Converging experiments where pitch strength is
      manipulated in different ways suggest that there may be a "pitch center" in the
      lateral part of Heschl's gyrus, adjacent to the primary auditory area. The
      suggestion is that there is a representation in this area that correlates with
      the perception of pitch rather than a simple mapping of physical stimulus
      characteristics. The analysis of patterns of pitch such as melodies, as opposed
      to the pitch of individual notes, involves much more distributed processing in
      the superior temporal lobes and frontal lobes. Involvement of the frontal lobe in
      pitch pattern analysis may in part reflect whether subjects analyze the pitch
      patterns in order to carry out an output task.

PMID- 14681117
TI  - Music agnosia and auditory agnosia. Dissociations in stroke patients.
AB  - A review and an experimental study were carried out in search of dissociations
      between the recognition of music (music agnosia) and that of environmental sounds
      (auditory agnosia) in stroke patients. The review focused on 45 adequately
      studied cases published since 1883. The experimental study consisted of
      administering standard tests of music and environmental sound recognition to 40
      unselected patients with unilateral stroke. Among case reports, music was
      selectively impaired more frequently than environmental sounds, whereas the
      reverse occurred in the experimental study. In this, right hemisphere lesions
      tended either to disrupt the apperception of environmental sounds, sparing music
      entirely, or to disrupt both environmental sounds and melody, sparing rhythm,
      whereas left hemisphere lesions tended to spare melody and to disrupt rhythm,
      either selectively or in association with the semantic identification of
      environmental sounds.

PMID- 14681118
TI  - Varieties of musical disorders. The Montreal Battery of Evaluation of Amusia.
AB  - Multiple disorders of musical abilities can occur after brain damage. Conversely,
      early brain anomalies or vast brain injuries may sometimes spare ordinary musical
      skills in individuals who experience severe cognitive losses. To document these
      incidences, comprehensive behavioral testing is required. We propose to use the
      Montreal Battery of Evaluation of Amusia (MBEA) because it is arguably the best
      tool currently available. Over the last decade, this battery was developed and
      validated in populations with brain damage of various etiologies. Furthermore,
      the MBEA is theoretically motivated and satisfies important psychometric
      properties. It is sensitive, normally distributed, reliable on test-retest, and
      correlates with Gordon's Musical Aptitude Profile, another more widely used
      battery of tests. To promote its wide usage, the MBEA is now available upon
      request. In addition, individual MBEA data of 160 normal participants of variable
      age and education have been made available to all via the internet.

PMID- 14681119
TI  - Music and the brain. Lessons from brain diseases and some reflections on the
      "emotional" brain.
AB  - Studies are reviewed from the perspective of a neurologist and epileptologist
      interested in "music and the brain." At the neurocognitive level, deficits in
      pitch discrimination of patients with brain lesions and those during the
      intracarotid amobarbital test are outlined, because they show that the temporal
      lobe and, in particular, the right acoustic cortex are crucial. Hallucinations of
      music during epileptic seizures as well as the analysis of musicogenic epilepsy
      point to the same gross localization and lateralization. At the esthetic level,
      music theoretical concepts on the consonance-dissonance dichotomy and related EEG
      examinations are reported, which illustrate the importance of mesiolimbic
      temporal lobe structures for the pleasure that we might experience when listening
      to music. The complex interaction of many neuronal circuits and assemblies of
      both hemispheres in musical perception and performance is illustrated by musical
      analysis of a recording by an organ player who experienced a right temporal lobe
      seizure. This analysis revealed that the seizure-induced errors of the left hand
      were compensated with the right hand in a musically meaningful way.

PMID- 14681120
TI  - Musicogenic seizures.
AB  - Eighty-seven reports of patients with seizures induced by listening and/or
      playing music and one personal observation are reviewed. Music-induced (or
      musicogenic) seizures are currently classified among the reflex seizures
      precipitated by complex stimuli. According to the available information, they are
      defined as focal seizures due to a discharge involving lateral and mesial
      temporal and orbitofrontal areas. The specific musical component responsible for
      seizure precipitation is still undetermined. An important role is attributed to
      the emotional aspect of music. The existence of this rare disorder should be
      borne in mind by neurologists, who should also be aware of the existing musical
      test batteries that may help in understanding better the nature of triggering
      mechanisms responsible for this unique pathological condition. The
      implementations of the results of ongoing investigations on brain processing of
      musical information will advance our understanding of the mechanisms responsible
      for the transition from interictal to ictal phases of epilepsy.

PMID- 14681121
TI  - Roundtable I: Dissecting the perceptual components of music. Introduction.

PMID- 14681122
TI  - Music as a biocultural phenomenon.
AB  - There is a need to clarify the domain of music as an object of cognitive and
      neuroscientific research. This paper explores some ramifications of an inclusive
      delineation of the domain of music for such research.

PMID- 14681123
TI  - Exploring the influence of cultural familiarity and expertise on neurological
      responses to music.
AB  - Contemporary music education in many countries has begun to incorporate not only
      the dominant music of the culture, but also a variety of music from around the
      world. Although the desirability of such a broadened curriculum is virtually
      unquestioned, the specific function of these musical encounters and their
      potential role in children's cognitive development remain unclear. We do not know
      if studying a variety of world music traditions involves the acquisition of new
      skills or an extension and refinement of traditional skills long addressed by
      music teachers. Is a student's familiarity with a variety of musical traditions a
      manifestation of a single overarching "musicianship" or is knowledge of these
      various musical styles more similar to a collection of discrete skills much like
      learning a second language? Research on the comprehension of spoken language has
      disclosed a neurologically distinct response among subjects listening to their
      native language rather than an unfamiliar language. In a recent study comparing
      Western subjects' responses to music of their native culture and music of an
      unfamiliar culture, we found that subjects' activation did not differ on the
      basis of the cultural familiarity of the music, but on the basis of musical
      expertise. We discuss possible interpretations of these findings in relation to
      the concept of musical universals, cross-cultural stimulus characteristics, cross
      cultural judgment tasks, and the influence of musical expertise. We conclude with
      suggestions for future research.

PMID- 14681124
TI  - Analysis and modeling of expressive intentions in music performance.
AB  - A performer can convey different expressive intentions when playing a piece of
      music. Perceptual and acoustic analysis of expressive music performances attempts
      to understand the musicians' strategies. Moreover, models for rendering different
      expressive intentions were developed for both analysis and deeper multimedia
      products fruition.

PMID- 14681125
TI  - Musicians versus nonmusicians. A neurophysiological approach.
AB  - The ability to perceive sounds and correctly categorize them within a scale is
      the result of the interaction between inherited capabilities and acquired rules.
      If a subject listens to a melody, occasional and unexpected endings of the melody
      typically evoke characteristic auditory evoked responses in the latency range of
      300-400 ms (P300). Also, earlier stages of auditory information processing have
      been exhaustively investigated by means of mismatch negativity (MMN), a
      deflection that occurs in the auditory evoked response at a latency of about 200
      ms, whenever a deviance is randomly inserted in a series of otherwise equal
      stimuli. Conceivably, perceptual deviations could also be detected against
      expectancies that are based on abstract rules; introspective experience suggests
      that such deviations may also elicit fast intuitive responses that typically
      initiate processes of analytical reasoning for confirmation. In music, the
      physical features of the stimulus are, in fact, always changing, because the
      melodic contour consists of a series of notes with different pitch
      characteristics. In such a condition, a typical mismatch negativity would not be
      evoked on the basis of physical deviance, but rather of criteria involving the
      musical contour of the stimulus. In this study, 20 healthy subjects (10
      nonmusicians and 10 musicians) underwent auditory stimulation (tone, chord, chord
      sequence, Mozart and Bach melodies) and both electrical and magnetic recordings.
      Clear N1 was recorded for all paradigms, in all subjects; MMN and P300 were also
      recorded, and their amplitudes and latencies were significantly correlated with
      the musicality score and with the paradigm's difficulty.

PMID- 14681126
TI  - Specialization of the specialized: electrophysiological investigations in
      professional musicians.
AB  - Several event-related brain potential (ERP) studies examining the processing of
      auditory stimuli by professional musicians compared with non-musicians are
      reviewed. In the first study, musicians (string players) and non-musicians
      attended to one of two streams of auditory stimuli characterized by a specific
      pitch. Musicians showed a prolonged ERP attention effect, the late portion of
      which was more frontally distributed than was that of the non-musicians. In the
      second study, we investigated auditory spatial processing in conductors,
      pianists, and nonmusicians. Only the conductors showed behavioral selectivity of
      sound sources located in the peripheral auditory space. In addition, this group
      showed a negative/positive mismatch response for deviant stimuli occurring
      outside the focus of spatial attention. Finally, a group of drummers was compared
      to woodwind players and nonmusicians in a passive listening task. A real
      continuous drum sequence was manipulated so that some beats were anticipated by
      80 ms. The drummers showed a mismatch response not only for the anticipated beats
      but also for the subsequent beats, suggesting a more complex representation of
      the temporal aspects stimulus sequence in this subject group. Together, these
      studies suggest qualitative differences of the neural correlates of auditory
      processing between musicians and non-musicians. Moreover, these differences
      appear to be shaped by the specific training of a musician.

PMID- 14681127
TI  - Rhythm in language and music: parallels and differences.
AB  - Rhythm is widely acknowledged to be an important feature of both speech and
      music, yet there is little empirical work comparing rhythmic organization in the
      two domains. One approach to the empirical comparison of rhythm in language and
      music is to break rhythm down into subcomponents and compare each component
      across domains. This approach reveals empirical evidence that rhythmic grouping
      is an area of overlap between language and music, but no empirical support for
      the long-held notion that language has periodic structure comparable to that of
      music. Focusing on the statistical patterning of event duration, new evidence
      suggests that the linguistic rhythm of a culture leaves an imprint on its musical
      rhythm. The latter finding suggests that one effective strategy for comparing
      rhythm in language and music is to determine if differences in linguistic rhythm
      between cultures are reflected in differences in musical rhythm.

PMID- 14681128
TI  - Neuropsychological studies of musical timbre.
AB  - Musical timbre is a multidimensional property of sound that allows one to
      distinguish musical instruments. In this paper, studies that explore the cerebral
      substrate underlying the processing of musical timbre are discussed. Perceptual
      asymmetries measured in normal participants, deficits of musical timbre
      perception obtained in brain-damaged patients, as well as results obtained with
      various neuroimaging methods are reviewed. The findings obtained in all of these
      studies generally support the predominant involvement of right temporal lobe
      areas, and more specifically of its anterior part, in processing spectral and
      temporal envelopes of musical timbre. However, controversies still exist about
      the contribution of the left temporal lobe in timbre perception. The necessity of
      comparing data obtained with different perceptual paradigms (same-different
      discrimination and similarity judgment) and various types of stimuli (single
      tones and melodies) was emphasized by reporting lesion studies carried out in
      patients with unilateral temporal lobe lesions. The few neuroimaging studies
      published in this domain provided additional and complementary findings. Unlike
      lesion studies that allow us to infer the cerebral structures that are essential
      for timbre perception, the latter investigations implicate a more distributed
      neural network in timbre processing that extends along the superior temporal
      gyrus to include not only anterior but also posterior temporal regions and
      possibly frontal areas as well.

PMID- 14681129
TI  - Recognition of interleaved melodies. An fMRI study.
AB  - An fMRI study of interleaved melody recognition was conducted to examine the
      neural basis of the bottom-up and top-down mechanisms involved in auditory stream
      segregation. Hemodynamic activity generated by a mixed sequence was recorded in
      eight listeners who were asked to recognize a target melody interleaved with
      distractor tones when the target was presented either before or after the
      composite sequence. fMRI results suggest that similar cortical networks were
      involved in both conditions, including bilaterally the auditory cortices within
      the superior temporal gyrus as well as the thalamus and the inferior frontal
      gyrus. However, when listeners heard the melody before they had to extract it
      from the mixture, neural activation in the inferior frontal operculum was
      significantly enhanced bilaterally; no change in auditory cortical activity was
      detected.

PMID- 14681130
TI  - Electrical brain responses to descriptive versus evaluative judgments of music.
AB  - The present study was aimed at finding neural correlates of aesthetic versus
      descriptive listening of the same musical cadences. Results showed that aesthetic
      listening generated greater right frontocentral negativities than did descriptive
      listening, indicating distinct cortical mechanisms for aesthetic versus
      descriptive processing of music.

PMID- 14681132
TI  - Estimating internal drift and just noticeable difference in the perception of
      continuous tempo drift. A new method.
AB  - Is there such a thing as an internal representation of a "steady tempo" and is
      this representation itself free from tempo drift? To investigate this question,
      we propose a new method for studying detection of continuous tempo drift.

PMID- 14681131
TI  - Cortical correlates of acquired deafness to dissonance.
AB  - Patient I.R., who had bilateral lesions in the auditory cortex but intact
      hearing, did not distinguish dissonant from consonant musical excerpts in
      behavioral testing. We additionally found that the electrical brain responses did
      not differentiate musical intervals in terms of their dissonance/consonance,
      consistent with the idea that this phenomenon depends on the integrity of
      cortical functions.

PMID- 14681133
TI  - Congenital amusia interferes with the ability to synchronize with music.
AB  - Eight adults with a music-specific learning disability (i.e., tone deafness, but
      we prefer the term "congenital amusia") were asked to tap along with music (e.g.,
      Ravel's Bolero) and with nonmusical isochronous sequences (i.e., noise bursts).
      The amusic persons' tapping performance was poorly synchronized with music
      compared to that of nine matched control participants. By contrast,
      synchronization with the noise bursts was normal, suggesting that amusic persons'
      timing difficulty is limited to music.

PMID- 14681134
TI  - Exploration of roughness by means of the mismatch negativity paradigm.
AB  - A mismatch negativity study was set up to find the neural correlates of roughness
      perception. The results suggest that when the sounds are not attended to,
      roughness is reflected by the mismatch positivity as evidenced at the mastoid
      electrodes.

PMID- 14681135
TI  - "Out-of-pitch" but still "in-time". An auditory psychophysical study in
      congenital amusic adults.
AB  - Congenital amusia is a lifelong disability, commonly known as tone deafness, that
      prevents afflicted individuals from developing basic musical skills despite
      normal audiometry and above-average intellectual, memory, and language skills.
      Although it is estimated that 4% of the general population would be born with
      such a musical handicap, the underlying cause is presently unknown. Recently, we
      proposed that this disorder could be traced to a deficit in pitch perception on
      the basis of a single case. Here we provide psychophysical evidence for the
      existence of a generalized defect that is both fine grained and specific to pitch
      because time is unaffected.

PMID- 14681136
TI  - Evoked potentials of the human auditory cortex: sensitive to the harmonic series?
AB  - Cortically generated auditory evoked potentials (N1 and P2) were recorded to
      frequency changes of harmonic and inharmonic complex tones comprising four
      sinusoidal components. The responses obtained when the frequencies suddenly
      became stationary after a period of 16/s changes were significantly shorter in
      latency when the frequencies were harmonically related, possibly implying a
      process of periodicity detection.

PMID- 14681137
TI  - Evoked potentials to test rhythm perception theories.
AB  - The general aim of this study was to investigate how rhythmic information is
      processed by the brain and how a mental representation of a rhythm leads to
      expectancies about events in the near future. We investigate this by means of EEG
      recordings from which evoked potentials (EPs), resulting from sensory and
      cognitive neural activity, are extracted.

PMID- 14681138
TI  - Perceiving musical scale structures. A cross-cultural event-related brain
      potentials study.
AB  - In this study, event-related brain potentials (ERPs) are used to investigate the
      processing of musical scale structures from a cross-cultural perspective. ERP
      reactions reveal that universal listening strategies per se are modified by
      culture.

PMID- 14681139
TI  - Singing: a selective deficit in the retrieval of musical intervals.
AB  - A case of dissociation between discrimination and retrieval of musical
      information in a patient with a lesion of the right hemisphere is described. This
      patient has lost the ability to correctly retrieve a musical interval when
      required to sing. This occurs in the presence of unimpaired interval
      discrimination and correct retrieval of temporal patterns and melodic contour
      (direction).

PMID- 14681140
TI  - Audiovisual interactions in music reading. A reaction times and event-related
      potentials study.
AB  - The general aim of this experiment was to investigate the processes involved in
      reading musical notation and to study the relationship between written music and
      its auditory representation. Our main interest was to determine if musicians can
      develop expectancies for plausible or implausible auditory events on the sole
      basis of the visual score. Results showed that musicians can clearly expect
      auditory endings on the basis of visual information. These findings enliven the
      discussion on the question of whether music reading is actually music perception.

PMID- 14681141
TI  - Preattentive processing of lexical tone perception by the human brain as indexed
      by the mismatch negativity paradigm.
AB  - Mismatch negativity (MMN) was used to investigate the processing of the
      discrimination between native and non-native CV syllables in tonal languages. MMN
      elicited by the native word was greater than that elicited by the non-native
      word. Hearing a native-language deviant significantly altered the elicited MMN in
      both amplitude and scalp voltage field distribution, reflecting the presence of a
      long-term memory trace for spoken words in tonal languages.

PMID- 14681142
TI  - Becoming a pianist. An fMRI study of musical literacy acquisition.
AB  - Musically naive subjects were scanned using functional magnetic resonance imaging
      (fMRI) before and after they had been taught to read music and play keyboard.
      When subjects played melodies from musical notation after training, activation
      was seen in a cluster of voxels within the right superior parietal cortex
      consistent with the view that music reading involves spatial sensorimotor
      mapping.

PMID- 14681143
TI  - Activation of the inferior frontal cortex in musical priming.
AB  - Musical contexts influence the processing of target events. Our study
      investigated the neural correlates of processing related and unrelated musical
      events presented as the last chord of eight-chord sequences.

PMID- 14681144
TI  - Analyzing pitch chroma and pitch height in the human brain.
AB  - The perceptual pitch dimensions of chroma and height have distinct
      representations in the human brain: chroma is represented in cortical areas
      anterior to primary auditory cortex, whereas height is represented posterior to
      primary auditory cortex.

PMID- 14681145
TI  - Part II: Brain Sciences versus Music. Introduction.

PMID- 14681146
TI  - Chemically defined parallel pathways in the monkey auditory system.
AB  - The pathways ascending through the brain stem to the medial geniculate complex of
      the thalamus can be distinguished by immunostaining for the calcium binding
      proteins parvalbumin and calbindin and by the properties of the neurons in the
      subdivisions of the medial geniculate complex in which they terminate. The
      parvalbumin pathway, ascending from the central nucleus of the inferior
      colliculus, is the more direct and terminates in the ventral nucleus. The
      calbindin pathway is more diffuse in its origins and terminates in the dorsal and
      medial nuclei. Ventral nucleus neurons are sharply tuned, tonotopically organized
      and consistent in their responses. They project to core areas of the auditory
      cortex characterized by high parvalbumin immunoreactivity and by similar neuronal
      properties. Neurons in the dorsal and medial nuclei are not frequency specific or
      tonotopic and are labile in their responses. They project more diffusely to belt
      areas of the auditory cortex in which parvalbumin immunoreactivity is reduced and
      in which neuronal responses are less specific than in the core. The belt areas
      are the origins of streams of corticocortical connections leading into the
      temporal, parietal, and frontal lobes. These routes can be differentially engaged
      in functional imaging studies of monkeys responding to biologically significant
      sounds.

PMID- 14681147
TI  - Musical skills and neural functions. The legacy of the brains of musicians.
AB  - An overview of the history of debates on the correlation of musical skills with
      neurological functions in health and disease is presented. Selected biographical
      sketches of composers (Hildegard von Bingen, Mozart, Donizetti, Mussorgsky, and
      Ravel), whose neurological disease may have influenced musical creativity, are
      discussed. The search for information on the localization of skills in the brains
      of musicians is reviewed. The relation of mental ability to brain structure is a
      prominent theme in the history of neuroscience, and the effort to localize
      musical skills dates back to the excesses of phrenology in the early nineteenth
      century. The phrenological tables included an "organ of music" among the sites
      subserving intellectual capabilities, mapped on the basis of palpation of the
      head bumps. Since the second half of the nineteenth century, when the study of
      brain physiology, anatomy, and pathology had a remarkable development and impact
      on the neurosciences, structural features of the brain, particularly the cerebral
      cortex, of individuals with peculiar talents, including musical skills, have been
      examined to search for clues on the localization of mental phenomena. These
      studies, which continued in the twentieth century, are currently difficult to
      validate in view of the rigor imposed by current scientific standards. However,
      the issue of localization of functions in the musical brain is still debated and
      is now at the forefront of the neurosciences, exploiting especially functional
      neuroimaging. The historical overview of these problems is certainly exemplary of
      progress of knowledge, but also warns against excessive "localizationist"
      efforts.

PMID- 14681148
TI  - Brain processing of meter and rhythm in music. Electrophysiological evidence of a
      common network.
AB  - To determine cortical structures involved in "global" meter and "local" rhythm
      processing, slow brain potentials (DC potentials) were recorded from the scalp of
      18 musically trained subjects while listening to pairs of monophonic sequences
      with both metric structure and rhythmic variations. The second sequence could be
      either identical to or different from the first one. Differences were either of a
      metric or a rhythmic nature. The subjects' task was to judge whether the
      sequences were identical or not. During processing of the auditory tasks, brain
      activation patterns along with the subjects' performance were assessed using 32
      channel DC electroencephalography. Data were statistically analyzed using MANOVA.
      Processing of both meter and rhythm produced sustained cortical activation over
      bilateral frontal and temporal brain regions. A shift towards right hemispheric
      activation was pronounced during presentation of the second stimulus. Processing
      of rhythmic differences yielded a more centroparietal activation compared to
      metric processing. These results do not support Lerdhal and Jackendoff's two
      component model, predicting a dissociation of left hemispheric rhythm and right
      hemispheric meter processing. We suggest that the uniform right temporofrontal
      predominance reflects auditory working memory and a pattern recognition module,
      which participates in both rhythm and meter processing. More pronounced parietal
      activation during rhythm processing may be related to switching of task-solving
      strategies towards mental imagination of the score.

PMID- 14681149
TI  - Perceptual and structural implications of "Virtual" music on the web.
AB  - The development of Cathedral, one of the first interactive works of music and art
      on the World Wide Web; the development of new virtual instruments, such as the
      PitchWeb, that allow listeners to participate actively and creatively; and the
      possibility that a new form of music is emerging are discussed. This new music,
      Virtual Music, is a new art form, within a new medium, producing a new type of
      interactive artistic experience, with the ability to draw in and engage its
      listeners in the creative process.

PMID- 14681150
TI  - Propositional music from extended musical interface with the human nervous
      system.
AB  - Results obtained from projects in which self-organizing musical structures
      spontaneously arise through electrical interface between the brain and generative
      musical systems are surveyed. This provides a springboard for examining important
      paradigm shifts taking place in our thinking about what musical forms can be and
      how this might influence efforts to increase our understanding of the underlying
      neural dynamics. Implications of this work for the design of music curricula are
      considered, emphasizing the importance of active imaginative listening. A view of
      composing, termed "propositional music," is introduced in which the proposition
      of cognitive models of music is an ongoing part of creative musical activity.

PMID- 14681151
TI  - The perception of microsound and its musical implications.
AB  - Sound particles or microsounds last only a few milliseconds, near the threshold
      of auditory perception. We can easily analyze the physical properties of sound
      particles either individually or in masses. However, correlating these properties
      with human perception remains complicated. One cannot speak of a single time
      frame, or a "time constant" for the auditory system. The hearing mechanism
      involves many different agents, each of which operates on its own timescale. The
      signals being sent by diverse hearing agents are integrated by the brain into a
      coherent auditory picture. The pioneer of "sound quanta," Dennis Gabor (1900
      1979), suggested that at least two mechanisms are at work in microevent
      detection: one that isolates events, and another that ascertains their pitch.
      Human hearing imposes a certain minimum duration in order to establish a firm
      sense of pitch, amplitude, and timbre. This paper traces disparate strands of
      literature on the topic and summarizes their meaning. Specifically, we examine
      the perception of intensity and pitch of microsounds, the phenomena of tone
      fusion and fission, temporal auditory acuity, and preattentive perception. The
      final section examines the musical implications of microsonic analysis,
      synthesis, and transformation.

PMID- 14681152
TI  - Translation from neurobiological data to music parameters.
AB  - Composers have explored different ways to use biological information for the
      realization of music. Throughout the decades, biological findings have been
      repeatedly indicated as a source of inspiration or a reservoir of extramusical
      material for musical composition. More radical and fertile are attempts to
      produce music systematically using biological data in processes called data
      sonification or biofeedback techniques. Presented here is a novel strategy of
      translation where populations of neurobiological data are converted into
      relational structures from which sound objects are generated by flexible and
      homogeneous control of the sound parameters. All brain data originate from
      experiments performed with standard anatomical and physiological techniques, and
      results of studies based on these experimental materials have already been
      published. During the translation processes, the information for every sound
      parameter (such as pitch, duration, envelope, and dynamics) is never derived from
      fixed transcriptions of data properties. Rather, the space and/or the time
      interrelations of data populations are used to obtain indexes for sound
      construction. In this way, equivalent sets of information are exploited to model,
      or sculpt, the different parameters of sound objects. Three examples from the
      last decade's personal productions are given. The first refers to the microformal
      aspects of sound aggregation and is based on data from a microstimulation
      experiment in the motor cortex. The second describes the earliest translation
      process developed for live performance with conventional instruments and is based
      on experiments using a conventional tract tracing technique to compare selected
      spinal-projecting cell populations in two differently organized brains. The third
      outlines a recent music production for three pianos based on data from
      experiments using the multiple fluorescent tract-tracing technique to
      simultaneously label different populations of thalamocortical neurons. The
      approach here described can potentially contribute to a unitary view of the
      different sound parameters and of the micro- and macroformal aspects of the
      compositional process.

PMID- 14681153
TI  - Roundtable II: A common high-level ground for scientists and musicians.
      Introduction.

PMID- 14681154
TI  - More about the musical expertise of musically untrained listeners.
AB  - Several behavioral experiments that were designed to compare the abilities of
      musicians and nonmusicians to process subtle changes in musical structures are
      surveyed. These experiments deal with different aspects of music perception
      including the processing of melodic and harmonic structures, the processing of
      large-scale structures, and implicit learning. In all these experiments, the so
      called nonmusician listeners behaved in a very similar way as did highly trained
      students from music conservatories and music departments. This outcome suggests
      that when the experimental setting requires participants to process musical
      structures (in contrast to musical tones), the large audience of untrained
      listeners exhibits sophisticated musical abilities that are similar to those of
      musical experts. It has been suggested that musically untrained listeners are
      "experienced listeners" who use the same principles as musical experts in
      organizing their hearing of music.

PMID- 14681155
TI  - Neurobiology of rhythmic motor entrainment.
AB  - Timing is extremely important for movement, and understanding the neurobiological
      basis of rhythm perception and reproduction can be helpful in addressing motor
      recovery after brain lesions. In this quest, the science of music might provide
      interesting hints for better understanding the brain timing mechanism. The report
      focuses on the neurobiological substrate of sensorimotor transformation of time
      data, highlighting the power of auditory rhythmic stimuli in guiding motor acts.
      The cerebellar role of timing is addressed in subjects with cerebellar damage;
      subsequently, cerebellar timing processing is highlighted through an fMRI study
      of professional musicians. The two approaches converge to demonstrate that
      different levels of time processing exist, one conscious and one not, and to
      support the idea that timing is a distributed function. The hypothesis that
      unconscious motor responses to auditory rhythmic stimuli can be relevant in
      guiding motor recovery and modulating music perception is advanced and discussed.

PMID- 14681156
TI  - Brain and sound resonance. The world of self-generative functions as a basis of
      the spectral language of music.
AB  - The author discusses the "preferential phenomenology" of sound spectra. Most
      interesting have been the sound relations that result from special filtering
      according to "rings" of resonance. Mathematical operations are required to
      describe this filtering of frequency multiples-spectral components-producing sum
      and difference tones. With new harmonic formats, a new phenomenological
      vocabulary of music is achieved that evolves far beyond its historical language.

PMID- 14681157
TI  - Neural basis of rhythmic timing networks in the human brain.
AB  - The study of rhythmicity provides insights into the understanding of temporal
      coding of music and temporal information processing in the human brain. Auditory
      rhythms rapidly entrain motor responses into stable steady synchronization states
      below and above conscious perception thresholds. Studying the neural dynamics of
      entrainment by measuring brain wave responses (MEG) we found nonlinear scaling of
      M100 amplitudes generated in primary auditory cortex relative to changes in the
      period of the rhythmic interval during subliminal and supraliminal tempo
      modulations. In recent brain imaging studies we have described the neural
      networks involved in motor synchronization to auditory rhythm. Activated regions
      include primary sensorimotor and cingulate areas, bilateral opercular premotor
      areas, bilateral SII, ventral prefrontal cortex, and, subcortically, anterior
      insula, putamen, and thalamus. Within the cerebellum, vermal regions and anterior
      hemispheres ipsilateral to the movement became significantly activated. Tracking
      temporal modulations additionally activated predominantly right prefrontal,
      anterior cingulate, and intraparietal regions as well as posterior cerebellar
      hemispheres. Furthermore, strong evidence exists for the substantial benefits of
      rhythmic stimuli in rehabilitation training with motor disorders.

PMID- 14681158
TI  - Effects of relaxing music on salivary cortisol level after psychological stress.
AB  - The goal of the present study was to determine whether relaxing music (as
      compared to silence) might facilitate recovery from a psychologically stressful
      task. To this aim, changes in salivary cortisol levels were regularly monitored
      in 24 students before and after the Trier Social Stress Test. The data show that
      in the presence of music, the salivary cortisol level ceased to increase after
      the stressor, whereas in silence it continued to increase for 30 minutes.

PMID- 14681159
TI  - Effect of unilateral temporal lobe resection on short-term memory for auditory
      object and sound location.
AB  - To investigate auditory spatial and nonspatial short-term memory, a sound
      location discrimination task and an auditory object discrimination task were used
      in patients with medial temporal lobe resection. The results showed a double
      dissociation between the side of the medial temporal lobe lesion and the nature
      of the auditory discrimination deficits, suggesting that right and left temporal
      lobe structures are differently involved in auditory spatial and nonspatial short
      term memory.

PMID- 14681160
TI  - Implicit and explicit emotional memory for melodies in Alzheimer's disease and
      depression.
AB  - The present study investigates the impact of emotional deficits on implicit and
      explicit memory for musical stimuli in patients with Alzheimer's disease and
      elderly depressed patients. Results showed that unlike Alzheimer's patients,
      depressed patients were unable to develop a positive affective bias of judgment
      for previously heard melodies.

PMID- 14681161
TI  - Musicians differ from nonmusicians in brain activation despite performance
      matching.
AB  - Brain activation patterns in a group of musicians and a group of nonmusicians
      (matched in performance score to the musician group) were compared during a pitch
      memory task using a sparse-temporal sampling functional magnetic resonance
      imaging experiment. Both groups showed bilateral activaton (left more than right)
      of the superior temporal gyrus, supramarginal gyrus, posterior middle and
      inferior frontal gyrus, and superior parietal lobe. Musicians showed greater
      right posterior temporal and supramarginal activation, whereas nonmusicians had
      greater activation of the left secondary auditory cortex.

PMID- 14681162
TI  - Part III: Music and Development. Introduction.

PMID- 14681163
TI  - Introductory remarks on musical beginnings: ten years later.
AB  - Over the last 10 years, the neurosciences have witnessed an exponential increase
      of research in the neuropsychology of music. Consequently, old and new questions
      on the ontogeny of musical skills can be refined and reformulated with greater
      accuracy. Three interrelated issues are discussed.

PMID- 14681164
TI  - Musical learning and language development.
AB  - How do infant learners acquire structure, given complex environments? In this
      chapter, we consider the role played by statistical learning-tracking patterns in
      the environment-in the acquisition of language and music. The results from a
      series of experiments suggest that similar learning mechanisms may operate in
      both domains, but that these mechanisms are also influenced by domain-specific
      perceptual biases and input structure.

PMID- 14681165
TI  - Toward a developmental psychology of music.
AB  - Research on music perception has revealed numerous parallels between infants and
      adults, but these findings have had little influence on adult research. Studies
      of pitch memory in infants, children, and adults are presented to illustrate
      potential gains from a developmental approach. Although the prevailing wisdom is
      that absolute pitch processing dominates in early life until it is supplanted by
      relative pitch processing, recent research offers no support for that view. After
      a week of exposure to English folk melodies, infants remember the melodies, but
      they do not distinguish the original versions from transposed versions. Relative
      pitch processing dominates later on, but it does not occur at the expense of
      absolute pitch processing. For example, adults can identify the pitch level of
      familiar musical recordings in the context of foils that are pitch shifted by one
      or two semitones. Children 5-9 years of age can identify the pitch level of
      familiar recordings when the foils are pitch shifted by two semitones but not by
      one semitone. By contrast, Japanese children are successful in the context of one
      semitone shifts. In short, a developmental approach can provide insights of
      comparable importance on many issues in music cognition.

PMID- 14681166
TI  - Experimental strategies for understanding the role of experience in music
      cognition.
AB  - Research in music cognition has assessed the role of experience by investigating
      the effects of development, training, and cross-cultural differences. A fourth
      approach is to apply statistical techniques to identify patterns that are
      relatively frequent in the listeners' musical experience. As an example of this
      approach, a functional magnetic resonance imaging (fMRI) study was conducted on
      melodic expectancy. Two patterns that frequently began musical themes in
      classical and folk music were identified. A final continuation tone was added to
      these opening patterns. Some of the continuation tones were frequent in the
      musical styles; others were infrequent. Listeners judged how well the
      continuation tones fit with their expectations. A sparse-sampling (event-related)
      design was used in the fMRI study, with image acquisition at varying delays after
      the sequence. Early acquisitions showed activation in the auditory cortex, and
      late acquisitions showed effects of the motor response. These results suggest the
      timing of the image acquisitions was appropriate. Contrasting melodies and
      monotonic controls showed right inferior frontal activation, similar to that
      found in other studies. However, no differences were found as a function of
      whether or not the continuation tone was frequent or infrequent in the
      statistical style analysis. Methodological differences of this study from other
      recent fMRI studies on harmonic expectations are discussed.

PMID- 14681167
TI  - Synchronizing with music: intercultural differences.
AB  - The way in which listeners perceive music changes throughout childhood, but
      little is known about the factors responsible for these changes. One factor,
      explicit music training, has received considerable attention, with studies
      indicating that musicians demonstrate a more complex hierarchical mental
      representation for music and superior temporal organizational skills. But does
      acculturation-the passive exposure to a particular type of music since birth-also
      influence the acquisition of these skills? We compared the music synchronization
      performance of Tunisian and French subjects with music from these two contrasting
      musical cultures. Twelve musical excerpts were selected from the two popular
      music cultures, matched for perceived tempo, complexity, and familiarity, and
      subjects were asked to tap in time with the music. Tapping mode (rate and
      hierarchical level) varied with subjects' familiarity with the musical idiom, as
      evidenced by an interaction between musical culture and type of music:
      participants synchronized at higher hierarchical levels (and over a wider range)
      with music from their own culture than with an unfamiliar type of music. Thus,
      passive acculturation as well as explicit music tuition influence our perception
      and cognition of music.

PMID- 14681168
TI  - Music and learning-induced cortical plasticity.
AB  - Auditory stimuli are encoded by frequency-tuned neurons in the auditory cortex.
      There are a number of tonotopic maps, indicating that there are multiple
      representations, as in a mosaic. However, the cortical organization is not fixed
      due to the brain's capacity to adapt to current requirements of the environment.
      Several experiments on cerebral cortical organization in musicians demonstrate an
      astonishing plasticity. We used the MEG technique in a number of studies to
      investigate the changes that occur in the human auditory cortex when a skill is
      acquired, such as when learning to play a musical instrument. We found enlarged
      cortical representation of tones of the musical scale as compared to pure tones
      in skilled musicians. Enlargement was correlated with the age at which musicians
      began to practice. We also investigated cortical representations for notes of
      different timbre (violin and trumpet) and found that they are enhanced in
      violinists and trumpeters, preferentially for the timbre of the instrument on
      which the musician was trained. In recent studies we extended these findings in
      three ways. First, we show that we can use MEG to measure the effects of
      relatively short-term laboratory training involving learning to perceive virtual
      instead of spectral pitch and that the switch to perceiving virtual pitch is
      manifested in the gamma band frequency. Second, we show that there is cross-modal
      plasticity in that when the lips of trumpet players are stimulated (trumpet
      players assess their auditory performance by monitoring the position and pressure
      of their lips touching the mouthpiece of their instrument) at the same time as a
      trumpet tone, activation in the somatosensory cortex is increased more than it is
      during the sum of the separate lip and trumpet tone stimulation. Third, we show
      that musicians' automatic encoding and discrimination of pitch contour and
      interval information in melodies are specifically enhanced compared to those in
      nonmusicians in that musicians show larger functional mismatch negativity (MMNm)
      responses to occasional changes in melodic contour or interval, but that the two
      groups show similar MMNm responses to changes in the frequency of a pure tone.

PMID- 14681169
TI  - Biological and psychological correlates of exceptional performance in
      development.
AB  - The issue of exceptional performance is discussed from four perspectives: genetic
      distribution of high giftedness, gene-environment interaction, neurobiological
      findings, and the role of deliberate practice as well as environment in general.
      The genetic perspective is illustrated mainly by the emergenic and epigenetic
      model of Simonton, followed by the three types of gene-environment interaction
      (Scarr and McCartney). The neurological perspective focuses on the role of early
      practice for neurological representation and on hormonal changes during
      development. The perspective of deliberate practice summarizes the present state
      of affairs within this field of research. Finally, a distinction between
      different levels of excellent performance is proposed, arguing against the
      neglect of genius as a specific phenomenon among excellent performance.

PMID- 14681170
TI  - Prosodic and melodic processing in adults and children. Behavioral and
      electrophysiologic approaches.
AB  - The results of a series of experiments aimed at directly comparing the prosodic
      level of processing in language with the melodic level of processing in music are
      reported. The first series of experiments was conducted on adults, musicians and
      nonmusicians, and the second one on 7- to 9-year-old musician and nonmusician
      children. However, as this last study is still in progress, only preliminary
      results will be presented. The theoretic framework within which these experiments
      are taking place is described. The first problem concerns the specificity of the
      perceptive and cognitive computations necessary to perceive and understand
      language. We argue that comparing language with music can provide interesting
      insights into this complex issue. The second problem is linked to the
      relationship between different types of learning. Does early musical training
      influence the way in which musicians process some aspects of language as prosody?
      These two problems are considered and the results of the experiments are
      described.

PMID- 14681171
TI  - Young children's harmonic perception.
AB  - Harmony and tonality are two of the most difficult elements for young children to
      perceive and manipulate and are seldom taught in the schools until the end of
      early childhood. Children's gradual harmonic and tonal development has been
      attributed to their cumulative exposure to Western tonal music and their
      increasing experiential knowledge of its rules and principles. Two questions that
      are relevant to this problem are: (1) Can focused and systematic teaching
      accelerate the learning of the harmonic/tonal principles that seem to occur in an
      implicit way throughout childhood? (2) Are there cognitive constraints that make
      it difficult for young children to perceive and/or manipulate certain harmonic
      and tonal principles? A series of studies specifically addressed the first
      question and suggested some possible answers to the second one. Results showed
      that harmonic instruction has limited effects on children's perception of harmony
      and indicated that the drastic improvement in the perception of implied harmony
      noted approximately at age 9 is due to development rather than instruction. I
      propose that young children's difficulty in perceiving implied harmony stems from
      their attention behaviors. Older children have less memory constraints and more
      strategies to direct their attention to the relevant cues of the stimulus.
      Younger children focus their attention on the melody, if present in the stimulus,
      and specifically on its concrete elements such as rhythm, pitch, and contour
      rather than its abstract elements such as harmony and key. The inference of the
      abstract harmonic organization of a melody required in the perception of implied
      harmony is thus an elusive task for the young child.

PMID- 14681172
TI  - Do mental speed and musical abilities interact?
AB  - The relation between mental speed and musical ability was investigated. Seventeen
      subjects aged 3-7 years were divided into two subgroups: one (G1; n = 9)
      consisted of children who participated in an early childhood music program and
      who received informal musical guidance, but no special training; the other (G2; n
      = 8) consisted of highly talented young violin players who received intensive
      parental support and special training by daily deliberate practice. Mental and
      musical abilities of both groups were controlled by standardized tests (Kaufman's
      ABC and Gordon's PMMA) and compared with data taken from recordings of saccadic
      eye movement using online identification from an electrooculogram (EOG). Results
      of EOG measurement are referred to as "mental speed," which correlates highly
      with general mental abilities (intelligence). These results were compared with
      EOG scores taken from a larger sample of children of the same age range (n = 82)
      who received no music instruction. The grand average of their scores served as a
      reference line for mental speed, which is normally expected to be performed by an
      equivalent age group. Data in the two experimental groups did not differ
      statistically; however, all musically experienced children had a highly
      significant advantage in mental age (P <0.01) compared to the reference line of
      the normal population who did not exhibit any effect of training and practice.
      This indicates strong interaction between mental speed and music ability, which
      can be interpreted in terms of the expertise model and cognitive transfer
      effects.

PMID- 14681173
TI  - Dyslexia and music. From timing deficits to musical intervention.
AB  - The underlying causes of the language and literacy difficulties experienced by
      dyslexic children are not yet fully understood, but current theories suggest that
      timing deficits may be a key factor. Dyslexic children have been found to exhibit
      timing difficulties in the domains of language, music, perception and cognition,
      as well as motor control. The author has previously suggested that group music
      lessons, based on singing and rhythm games, might provide a valuable multisensory
      support tool for dyslexic children by encouraging the development of important
      auditory and motor timing skills and subsequently language skills. In order to
      examine this hypothesis, a research program was designed that involved the
      development of group music lessons and musical tests for dyslexic children in
      addition to three experimental studies. It was found that classroom music lessons
      had a positive effect on both phonologic and spelling skills, but not reading
      skills. Results also indicated that dyslexic children showed difficulties with
      musical timing skills while showing no difficulties with pitch skills. These
      apparent disassociations between spelling and reading ability and musical timing
      and pitch ability are discussed. The results of the research program are placed
      in the context of a more general model of the potential relationship between
      musical training and improved language and literacy skills.

PMID- 14681174
TI  - Effects of musical training on the auditory cortex in children.
AB  - Several studies of the effects of musical experience on sound representations in
      the auditory cortex are reviewed. Auditory evoked potentials are compared in
      response to pure tones, violin tones, and piano tones in adult musicians versus
      nonmusicians as well as in 4- to 5-year-old children who have either had or not
      had extensive musical experience. In addition, the effects of auditory frequency
      discrimination training in adult nonmusicians on auditory evoked potentials are
      examined. It was found that the P2-evoked response is larger in both adult and
      child musicians than in nonmusicians and that auditory training enhances this
      component in nonmusician adults. The results suggest that the P2 is particularly
      neuroplastic and that the effects of musical experience can be seen early in
      development. They also suggest that although the effects of musical training on
      cortical representations may be greater if training begins in childhood, the
      adult brain is also open to change. These results are discussed with respect to
      potential benefits of early musical training as well as potential benefits of
      musical experience in aging.

PMID- 14681175
TI  - Gray matter differences between musicians and nonmusicians.
AB  - Musicians learn complex motor and auditory skills at an early age and practice
      these specialized skills extensively from childhood through their entire careers.
      Using a voxel-by-voxel morphometric technique, we found gray matter volume
      differences in motor as well as auditory and visuospatial brain regions comparing
      professional musicians (keyboard players) with matched amateur musicians and
      nonmusicians. These multiregional differences might represent structural
      adaptations in response to long-term skill learning and repetitive rehearsal of
      these skills. This is supported by finding a strong association between
      structural differences, musician status, and practice intensity as well as by a
      wealth of supporting animal data showing structural changes in response to long
      term motor training.

PMID- 14681176
TI  - Toddlers' musical preferences: musical preference and musical memory in the early
      years.
AB  - The current paper reports a pilot study of the preferences of children aged 2-3.5
      years for different kinds of music. With the use of a novel interactive procedure
      to measure active preferences, preliminary results indicate general preferences
      for fast and loud music irrespective of style.

PMID- 14681177
TI  - Long-term memory for pitch in six-month-old infants.
AB  - We examined 6-month-old infants' long-term memory representations for the pitch
      of familiar melodies. Infants remembered the relative pitch of the melodies, but
      the absolute pitch was either not remembered or not a particularly salient
      attribute.

PMID- 14681178
TI  - Absolute pitch does not depend on early musical training.
AB  - The etiology and defining characteristics of absolute pitch (AP) have been
      controversial. To test the importance of musical training in the development of
      this skill, we developed a new paradigm for identifying AP that is independent of
      a subject's musical experience. We confirm the efficacy of the paradigm using
      classically defined AP and non-AP musicians. We then present data from a
      nonmusician who nevertheless appears to possess AP. We conclude that musical
      training is not necessary for the development of AP.

PMID- 14681179
TI  - Investigating the musical qualities of early infant sounds.
AB  - Early vocalizations in Italian and Moroccan infants are examined and the results
      presented.

PMID- 14681180
TI  - Perceiving prosody in speech. Effects of music lessons.
AB  - In two experiments, musically trained and untrained adults were tested on their
      ability to match spoken utterances with their tonal analogues (tone sequences
      that retained the pitch and temporal patterns of the utterances). In both cases,
      musical training was associated with superior performance, indicating an enhanced
      ability to extract prosodic information from spoken phrases.

PMID- 14681183
TI  - Lachesin is a component of a septate junction-based mechanism that controls tube
      size and epithelial integrity in the Drosophila tracheal system.
AB  - Organ morphogenesis requires the coordinated activity of many mechanisms involved
      in cell rearrangements, size control, cell proliferation and organ integrity.
      Here we report that Lachesin (Lac), a cell surface protein, is required for the
      proper morphogenesis of the Drosophila tracheal system. Homozygous embryos for
      Lac mutations, which we find fail to complement the previous identified bulbous
      (bulb) mutation, display convoluted tracheal tubes and tube breaks. At the
      cellular level, we can detect enlarged cells, suggesting that Lac regulates organ
      size by influencing cell length rather than cell number, and cell detachments,
      indicating a role for Lac in cell adhesion. Results from an in vitro assay
      further support that Lac behaves as a homophilic cell adhesion molecule. Lac co
      localizes with Septate Junction (SJ) proteins, and ultrastructural analysis
      confirms that it accumulates specifically at this type of cellular junction. In
      Lac mutant embryos, previously characterized components of the SJs are
      mislocalized, indicating that the proper organization of SJs requires Lac
      function. In addition, mutations in genes encoding other components of the SJs
      produce a similar tracheal phenotype. These results point out a new role of the
      SJs in morphogenesis regulating cell adhesion and cell size.

PMID- 14681184
TI  - Hyzic, the Hydra homolog of the zic/odd-paired gene, is involved in the early
      specification of the sensory nematocytes.
AB  - Cnidaria are the first class of organisms in animal evolution with a nervous
      system. The cnidarian Hydra has two types of neuronal cell, nerve cells and
      nematocytes. Both differentiate from the same pool of pluripotent stem cells.
      Yet, the molecular regulation of neural differentiation in Hydra is largely
      unknown. Here, we report the identification of Hyzic, a homolog of the Zn-finger
      transcription factor gene zic/odd-paired, which acts as an early neural effector
      gene in vertebrates. We show, that Hyzic is expressed in the early nematocyte
      differentiation pathway, starting at the level of interstitial stem cells.
      Expression of Hyzic is restricted to the proliferative stages of nematoblasts.
      Hyzic acts before and possibly directly upstream of Cnash, a homolog of the
      proneural bHLH transcription factor gene achaete-scute, and of Nowa, an early
      nematocyte differentiation marker gene. Hyzic may determine stem cells to
      differentiate into nematocytes. Our data are consistent with a role of Hyzic in
      inhibiting nematocyte differentiation, by keeping committed nematoblast cells in
      the cell cycle. A similar role has been demonstrated for Zic genes in
      vertebrates. Our results suggest, that genetic cascades of neural development may
      be conserved from Hydra to vertebrates, indicating that the molecular regulation
      of neural development evolved only once.

PMID- 14681185
TI  - 'Side Population' cells in adult mouse testis express Bcrp1 gene and are enriched
      in spermatogonia and germinal stem cells.
AB  - Stem cells in various somatic tissues (bone marrow, skeletal muscle) can be
      identified by the 'Side Population' marker based on Hoechst 33342 efflux. We show
      that mouse testicular cells also display a 'Side Population' that express Bcrp1
      mRNA, the ABC transporter responsible for Hoechst efflux in hematopoietic cells.
      Inhibition of Hoechst efflux by specific BCRP1 inhibitor Ko143 show that germinal
      'Side Population' phenotype is dependent on BCRP1 activity. Analysis of two well
      defined models of altered spermatogenesis (W/Wv mutants and cryptorchid male
      mice) and RNA expression studies of differentiation markers demonstrate that
      germinal 'Side Population' contains spermatogonial cells. In addition, alpha 6
      integrin and Stra8 germinal stem cell markers, are expressed in the 'Side
      Population'. In vivo repopulation assay clearly establishes that testis 'Side
      Population' in adult mice is highly enriched in male germ stem cells.

PMID- 14681186
TI  - DAF-5 is a Ski oncoprotein homolog that functions in a neuronal TGF beta pathway
      to regulate C. elegans dauer development.
AB  - An unconventional TGF beta superfamily pathway plays a crucial role in the
      decision between dauer diapause and reproductive growth. We have studied the daf
      5 gene, which, along with the daf-3 Smad gene, is antagonized by upstream
      receptors and receptor-regulated Smads. We show that DAF-5 is a novel member of
      the Sno/Ski superfamily that binds to DAF-3 Smad, suggesting that DAF-5, like
      Sno/Ski, is a regulator of transcription in a TGF beta superfamily signaling
      pathway. However, we present evidence that DAF-5 is an unconventional Sno/Ski
      protein, because DAF-5 acts as a co-factor, rather than an antagonist, of a Smad
      protein. We show that expressing DAF-5 in the nervous system rescues a daf-5
      mutant, whereas muscle or hypodermal expression does not. Previous work suggested
      that DAF-5 and DAF-3 function in pharyngeal muscle to regulate gene expression,
      but our analysis of regulation of a pharynx specific promoter suggests otherwise.
      We present a model in which DAF-5 and DAF-3 control the production or release of
      a hormone from the nervous system by either regulating the expression of
      biosynthetic genes or by altering the connectivity or the differentiated state of
      neurons.

PMID- 14681187
TI  - Partial loss-of-function alleles reveal a role for GNOM in auxin transport
      related, post-embryonic development of Arabidopsis.
AB  - The Arabidopsis GNOM gene encodes an ARF GDP/GTP exchange factor involved in
      embryonic axis formation and polar localisation of the auxin efflux regulator
      PIN1. To examine whether GNOM also plays a role in post-embryonic development and
      to clarify its involvement in auxin transport, we have characterised newly
      isolated weak gnom alleles as well as trans-heterozygotes of complementing strong
      alleles. These genotypes form a phenotypic series of GNOM activity in post
      embryonic development, with auxin-related defects, especially in the maintenance
      of primary root meristem activity and in the initiation and organisation of
      lateral root primordia. Our results suggest a model for GNOM action mediating
      auxin transport in both embryogenesis and post-embryonic organ development.

PMID- 14681188
TI  - Flow regulates arterial-venous differentiation in the chick embryo yolk sac.
AB  - Formation of the yolk sac vascular system and its connection to the embryonic
      circulation is crucial for embryo survival in both mammals and birds. Most mice
      with mutations in genes involved in vascular development die because of a failure
      to establish this circulatory loop. Surprisingly, formation of yolk sac arteries
      and veins has not been well described in the recent literature. Using time-lapse
      video-microscopy, we have studied arterial-venous differentiation in the yolk sac
      of chick embryos. Immediately after the onset of perfusion, the yolk sac exhibits
      a posterior arterial and an anterior venous pole, which are connected to each
      other by cis-cis endothelial interactions. To form the paired and interlaced
      arterial-venous pattern characteristic of mature yolk sac vessels, small caliber
      vessels of the arterial domain are selectively disconnected from the growing
      arterial tree and subsequently reconnected to the venous system, implying that
      endothelial plasticity is needed to fashion normal growth of veins. Arterial
      venous differentiation and patterning are controlled by hemodynamic forces, as
      shown by flow manipulation and in situ hybridization with arterial markers
      ephrinB2 and neuropilin 1, which show that expression of both mRNAs is not
      genetically determined but plastic and regulated by flow. In vivo application of
      ephrinB2 or EphB4 in the developing yolk sac failed to produce any morphological
      effects. By contrast, ephrinB2 and EphB4 application in the allantois of older
      embryos resulted in the rapid formation of arterial-venous shunts. In conclusion,
      we show that flow shapes the global patterning of the arterial tree and regulates
      the activation of the arterial markers ephrinB2 and neuropilin 1.

PMID- 14681189
TI  - Hedgehog-GLI signaling regulates the behavior of cells with stem cell properties
      in the developing neocortex.
AB  - Stem cells are crucial for normal development and homeostasis, and their
      misbehavior may be related to the origin of cancer. Progress in these areas has
      been difficult because the mechanisms regulating stem cell lineages are not well
      understood. Here, we have investigated the role of the SHH-GLI pathway in the
      developing mouse neocortex. The results show that SHH signaling endogenously
      regulates the number of embryonic and postnatal mouse neocortical cells with stem
      cell properties, and controls precursor proliferation in a concentration
      dependent manner in cooperation with EGF signaling. These findings identify a
      crucial mechanism for the regulation of the number of cells with stem cell
      properties that is unexpectedly conserved in different stem cell niches.

PMID- 14681190
TI  - The exocyst component Sec5 is required for membrane traffic and polarity in the
      Drosophila ovary.
AB  - The directed traffic of membrane proteins to the cell surface is crucial for many
      developmental events. We describe the role of Sec5, a member of the exocyst
      complex, in directed membrane traffic in the Drosophila oocyte. During oogenesis,
      we find that Sec5 localization undergoes dynamic changes, correlating with the
      sites at which it is required for the traffic of membrane proteins. Germline
      clones of sec5 possess defects in membrane addition and the posterior positioning
      of the oocyte. Additionally, the impaired membrane trafficking of Gurken, the
      secreted ligand for the EGF receptor, and Yolkless, the vitellogenin receptor,
      results in defects in dorsal patterning and egg size. However, we find the
      cytoskeleton to be correctly oriented. We conclude that Sec5 is required for
      directed membrane traffic, and consequently for the establishment of polarity
      within the developing oocyte.

PMID- 14681191
TI  - RABBIT EARS, encoding a SUPERMAN-like zinc finger protein, regulates petal
      development in Arabidopsis thaliana.
AB  - Floral organs usually initiate at fixed positions in concentric whorls within a
      flower. Although it is understood that floral homeotic genes determine the
      identity of floral organs, the mechanisms of position determination and the
      development of each organ have not been clearly explained. We isolated a novel
      mutant, rabbit ears (rbe), with defects in petal development. In rbe, under
      developed petals are formed at the correct position in a flower, and the
      initiation of petal primordia is altered. The rbe mutation affects the second
      whorl organ shapes independently of the organ identity. RBE encodes a SUPERMAN
      like protein and is located in the nucleus, and thus may be a transcription
      factor. RBE transcripts are expressed in petal primordia and their precursor
      cells, and disappeared at later stages. When cells that express RBE are ablated
      genetically, no petal primordia arise. RBE is not expressed in ap1-1 and ptl-1
      mutants, indicating that RBE acts downstream of AP1 and PTL genes. These
      characteristics suggest that RBE is required for the early development of the
      organ primordia of the second whorl.

PMID- 14681192
TI  - Both cyclin B levels and DNA-replication checkpoint control the early embryonic
      mitoses in Drosophila.
AB  - The earliest embryonic mitoses in Drosophila, as in other animals except mammals,
      are viewed as synchronous and of equal duration. However, we observed that total
      cell-cycle length steadily increases after cycle 7, solely owing to the extension
      of interphase. Between cycle 7 and cycle 10, this extension is DNA-replication
      checkpoint independent, but correlates with the onset of Cyclin B oscillation. In
      addition, nuclei in the middle of embryos have longer metaphase and shorter
      anaphase than nuclei at the two polar regions. Interestingly, sister chromatids
      move faster in anaphase in the middle than the posterior region. These regional
      differences correlate with local differences in Cyclin B concentration. After
      cycle 10, interphase and total cycle duration of nuclei in the middle of the
      embryo are longer than at the poles. Because interphase also extends in
      checkpoint mutant (grapes) embryo after cycle 10, although less dramatic than
      wild-type embryos, interphase extension after cycle 10 is probably controlled by
      both Cyclin B limitation and the DNA-replication checkpoint.

PMID- 14681194
TI  - Inactivation of mouse Twisted gastrulation reveals its role in promoting Bmp4
      activity during forebrain development.
AB  - Twisted gastrulation (Tsg) is a secreted protein that regulates Bmp signaling in
      the extracellular space through its direct interaction with Bmp/Dpp and Chordin
      (Chd)/Short gastrulation (Sog). The ternary complex of Tsg/Chd/Bmp is cleaved by
      the metalloprotease Tolloid (Tld)/Xolloid (Xld). Studies in Drosophila, Xenopus
      and zebrafish suggest that Tsg can act both as an anti-Bmp and as a pro-Bmp. We
      have analyzed Tsg loss-of-function in the mouse. Tsg homozygous mutants are
      viable but of smaller size and display mild vertebral abnormalities and
      osteoporosis. We provide evidence that Tsg interacts genetically with Bmp4. When
      only one copy of Bmp4 is present, a requirement of Tsg for embryonic development
      is revealed. Tsg-/-;Bmp4+/- compound mutants die at birth and display
      holoprosencephaly, first branchial arch and eye defects. The results show that
      Tsg functions to promote Bmp4 signaling during mouse head development.

PMID- 14681193
TI  - Interplay between Notch signaling and the homeoprotein Xiro1 is required for
      neural crest induction in Xenopus embryos.
AB  - The neural crest is a population of cells that originates at the interface
      between the neural plate and non-neural ectoderm. Here, we have analyzed the role
      that Notch and the homeoprotein Xiro1 play in the specification of the neural
      crest. We show that Xiro1, Notch and the Notch target gene Hairy2A are all
      expressed in the neural crest territory, whereas the Notch ligands Delta 1 and
      Serrate are expressed in the cells that surround the prospective crest cells. We
      have used inducible dominant-negative and activator constructs of both Notch
      signaling components and Xiro1 to analyze the role of these factors in neural
      crest specification without interfering with mesodermal or neural plate
      development. Activation of Xiro1 or Notch signaling led to an enlargement of the
      neural crest territory, whereas blocking their activity inhibited the expression
      of neural crest markers. It is known that BMPs are involved in the induction of
      the neural crest and, thus, we assessed whether these two elements might
      influence the expression of Bmp4. Activation of Xiro1 and of Notch signaling
      upregulated Hairy2A and inhibited Bmp4 transcription during neural crest
      specification. These results, in conjunction with data from rescue experiments,
      allow us to propose a model wherein Xiro1 lies upstream of the cascade regulating
      Delta 1 transcription. At the early gastrula stage, the coordinated action of
      Xiro1, as a positive regulator, and Snail, as a repressor, restricts the
      expression of Delta 1 at the border of the neural crest territory. At the late
      gastrula stage, Delta 1 interacts with Notch to activate Hairy2A in the region of
      the neural fold. Subsequently, Hairy2A acts as a repressor of Bmp4 transcription,
      ensuring that levels of Bmp4 optimal for the specification of the neural plate
      border are attained in this region. Finally, the activity of additional signals
      (WNTs, FGF and retinoic acid) in this newly defined domain induces the production
      of neural crest cells. These data also highlight the different roles played by
      BMP in neural crest specification in chick and Xenopus or zebrafish embryos.

PMID- 14681195
TI  - Expression of trophoblast cell-specific pregnancy-related genes in somatic cell
      cloned bovine pregnancies.
AB  - We compared the expression of bovine prolactin-related protein-1 (bPRP-1),
      placental lactogen (bPL), and pregnancy-associated glycoproteins-1 (bPAG-1) and 
      9 (bPAG-9) genes in artificially inseminated (AI) and nuclear transferred (NT)
      cows during the first trimester of gestation using real-time reverse
      transcription-polymerase chain reaction and in situ hybridization. Placentomal
      (cotyledonary, caruncular) and interplacentomal (intercotyledonary,
      intercaruncular) tissues of AI and NT cows carrying either motile (M) or immotile
      (IM) fetuses were examined. Transcripts for bPL and bPAG-9 were lower (P < 0.01)
      in the fetal membranes of NT (n = 4) cows at Day 30 of gestation, compared with
      AI (n = 4) cows. There was no difference in the mean (+/- SEM) levels of
      expressions of bPRP-1, bPL, and PAG-1 in the placentomal and interplacentomal
      tissues of AI (n = 5) and NT (M, n = 4) cows at Day 60 of gestation. The mRNAs
      for bPRP-1, bPL, bPAG-1, and bPAG-9 genes were higher (P < 0.01) in the
      caruncular tissue of AI cows, compared with NT (IM, n = 4) cows at Day 60 of
      gestation. Expression of bPRP-1, bPL, bPAG-1, and bPAG-9 in the placentomal and
      interplacentomal tissues of the NT (n = 3) group varied considerably more,
      compared with the AI (n = 4) group at Day 100 of gestation. These findings
      suggest defective binucleate cell-specific gene transcriptional commands in NT
      cows.

PMID- 14681197
TI  - Lineage, maturity, and phenotype of uterine murine dendritic cells throughout
      gestation indicate a protective role in maintaining pregnancy.
AB  - Dendritic cells (DCs) are known to play a major role in the induction,
      maintenance, and regulation of immune responses. Recently, DCs have been
      described to be present at the feto-maternal interface in human decidua. However,
      only limited information is available about DC presence, phenotype, and--more
      importantly--function throughout gestation. Thus, we analyzed local (uterine) and
      systemic (blood) DCs in a murine model. DBA/2J mated CBA/J females with vaginal
      plugs were separated and killed on Gestation Days (GDs) 1.5, 3.5, 5.5, 6.5, 7.5,
      8.5, 10.5, 13.5, 15.5, or 17.5. Frequency of uterine and blood CD11c+ DC,
      phenotype (coexpression of CD8alpha and major histocompatibility complex class II
      [MHC II] antigens), and presence of intracellular cytokines (interleukins 12 and
      10) were determined by flow cytometry. The morphology of DC in the pregnant
      uterus was evaluated by immunohistochemistry. In uterus, the relative number of
      CD11c+ cells increased from GD 5.5, reaching a plateau on GD 9.5 until GD 17.5,
      while a transient peak of systemic CD11c+ cells was found on GD 8.5 and 10.5. The
      vast majority of uterine DCs were CD8alpha- and thus, belonged to the myeloid
      lineage. Interestingly, a significant peak of lymphoid DC was present on GD 1.5
      and 5.5. Further, significantly more intracellular interleukin 10 than
      interleukin 12 was present in CD11c+ cells. Interestingly, mature DCs (MHC II+)
      were diminished from GD 5.5 to 8.5. Characterization of CD11c+ cell kinetics in
      uterus and blood reveals variation of phenotype during pregnancy, pointing toward
      an eminent immunoregulatory role of DCs throughout gestation at the feto-maternal
      interface.

PMID- 14681198
TI  - Developmental distribution of the polyadenylation protein CstF-64 and the variant
      tauCstF-64 in mouse and rat testis.
AB  - Messenger RNA polyadenylation is one of the processes that control gene
      expression in all eukaryotic cells and tissues. In mice, two forms of the
      regulatory polyadenylation protein CstF-64 are found. The gene Cstf2 on the X
      chromosome encodes this form, and it is expressed in all somatic tissues. The
      second form, tauCstF-64 (encoded by the autosomal gene Cstf2t), is expressed in a
      more limited set of tissues and cell types, largely in meiotic and postmeiotic
      male germ cells and, to a smaller extent, in brain. We report here that whereas
      CstF-64 and tauCstF-64 expression in rat tissues resembles their expression in
      mouse tissues, significant differences also are found. First, unlike in mice, in
      which CstF-64 was expressed in postmeiotic round and elongating spermatids, rat
      CstF-64 was absent in those cell types. Second, unlike in mice, tauCstF-64 was
      expressed at significant levels in rat liver. These differences in expression
      suggest interesting differences in X-chromosomal gene expression between these
      two rodent species.

PMID- 14681196
TI  - Glucocorticoid enhances transforming growth factor-beta effects on extracellular
      matrix protein expression in human placental mesenchymal cells.
AB  - Extracellular matrix (ECM) proteins synthesized by human placental mesenchymal
      cells (PMCs) provide structural support for the villus. Aberrant expression of
      ECM proteins by PMCs has been associated with intrauterine growth restriction
      (IUGR). To provide insight into the mechanisms of ECM protein regulation in the
      stroma of the placental villus, in the current study, we examined the interaction
      of glucocorticoid (GC) and transforming growth factor-beta (TGFbeta) in the
      modulation of ECM proteins in cultures of PMCs isolated from human term
      placentas. Initial results obtained by ELISA showed that combined treatment with
      dexamethasone (DEX) and TGFbeta enhanced oncofetal fibronectin (FFN) protein
      levels in serum-free culture medium severalfold in a dose-dependent manner.
      Northern blotting and real-time polymerase chain reaction (PCR) analyses revealed
      a similar enhancement in levels of FN mRNA in cells treated with TGFbeta and DEX.
      Real-time PCR results also revealed that DEX and TGFbeta enhanced collagen (Col)
      I and Col IV expression, but did not affect levels of Col III or laminin,
      indicative of selective stimulation of ECM proteins. Hypoxic treatment moderately
      enhanced FFN levels in control cells but not in those treated with DEX and
      TGFbeta. In contrast with the results obtained with PMCs, we noted that DEX
      treatment suppressed FFN levels in untreated and TGFbeta-treated
      cytotrophoblasts, suggesting that GC and TGFbeta modulate FFN expression in
      placenta in a cell-type-specific manner. We conclude that GC and TGFbeta are key
      regulators of ECM protein synthesis in PMCs, suggesting a role in modulating
      placental architecture in uncomplicated pregnancies and those associated with
      aberrant ECM protein expression.

PMID- 14681199
TI  - Nuclear-cytoplasmic interactions affect in utero developmental capacity,
      phenotype, and cellular metabolism of bovine nuclear transfer fetuses.
AB  - We generated a clone of bovine somatic cell nuclear transfer embryos using oocyte
      pools from defined maternal sources to study nuclear-cytoplasmic interactions.
      Nucleocytoplasmic hybrids were reconstructed with Bos taurus (Brown Swiss)
      granulosa cells and oocytes that contained B. taurus A (Simmental), B. taurus B
      (Simmental), or Bos indicus (Dwarf Zebu) cytoplasm. Another set of embryos was
      reconstructed with randomly selected Brown Swiss (B. taurus R) oocytes. Embryo
      transfer resulted in nine (12.5%), nine (13.8%), three (50%), and 11 (16.7%) Day
      80 fetuses, of which eight (11.1%), three (4.6%), three (50%), and 10 (15.2%)
      were viable, respectively. The proportion of viable fetuses was affected by
      cytoplasm (likelihood ratio test, P < 0.02) and was higher for embryos with B.
      indicus cytoplasm than for the B. taurus A (P < 0.05) and B (P < 0.01) groups.
      Furthermore, the proportion of surviving Day 80 fetuses was reduced for B. taurus
      B as compared with B. taurus A and B. taurus R cytoplasm (P < 0.05 and P < 0.02).
      Body weight of nucleocytoplasmic hybrid fetuses was not significantly different
      from Brown Swiss control fetuses produced by artificial insemination (AI), but
      fetuses reconstructed with random cytoplasts of the same breed as the nuclear
      donor exhibited overgrowth (P < 0.01) and a higher coefficient of variation in
      weight. Furthermore, body weight, crown rump length, thorax circumference (P <
      0.05), and femur length (P < 0.01) of fetuses with B. taurus A cytoplasm differed
      from fetuses with B. taurus R cytoplasms. Fetal skin, heart, and liver cells with
      B. indicus cytoplasm showed a greater increase in number per time period (P <
      0.001) and oxygen consumption rate per cell (skin and liver, P < 0.001; heart, P
      < 0.08) in comparison with their counterparts with B. taurus A cytoplasm. These
      data point to complex oocyte cytoplasm-dependent epigenetic modifications and/or
      nuclear DNA-mitochondrial DNA interactions with relevance to nuclear transfer and
      other reproductive technologies such as ooplasmic transfer in human assisted
      reproduction.

PMID- 14681200
TI  - Equol is a novel anti-androgen that inhibits prostate growth and hormone
      feedback.
AB  - Equol (7-hydroxy-3[4'hydroxyphenyl]-chroman) is the major metabolite of the
      phytoestrogen daidzein, one of the main isoflavones found abundantly in soybeans
      and soy foods. Equol may be an important biologically active molecule based on
      recent studies demonstrating that equol can modulate reproductive function. In
      this study, we examined the effects of equol on prostate growth and LH secretion
      and determined some of the mechanisms by which it might act. Administration of
      equol to intact male rats for 4-7 days reduced ventral prostate and epididymal
      weight and increased circulating LH levels. Using binding assays, we determined
      that equol specifically binds 5alpha-dihydrotestosterone (DHT), but not
      testosterone, dehydroepiandrosterone, or estrogen with high affinity. Equol does
      not bind the prostatic androgen receptor, and has a modest affinity for
      recombinant estrogen receptor (ER) beta, and no affinity for ERalpha. In
      castrated male rats treated with DHT, concomitant treatment with equol blocked
      DHT's trophic effects on the ventral prostate gland growth and inhibitory
      feedback effects on plasma LH levels without changes in circulating DHT.
      Therefore, equol can bind circulating DHT and sequester it from the androgen
      receptor, thus altering growth and physiological hormone responses that are
      regulated by androgens. These data suggest a novel model to explain equol's
      biological properties. The significance of equol's ability to specifically bind
      and sequester DHT from the androgen receptor have important ramifications in
      health and disease and may indicate a broad and important usage for equol in the
      treatment of androgen-mediated pathologies.

PMID- 14681201
TI  - Genetic variation in oocyte phenotype revealed through parthenogenesis and
      cloning: correlation with differences in pronuclear epigenetic modification.
AB  - Previous studies revealed that oocytes of different genetic strains (e.g, C57BL/6
      and DBA/2) modify maternal and paternal pronuclei differently, affecting early
      preimplantation development. To determine whether these strain-dependent effects
      would also apply to oocyte modifications of somatic cell nuclei introduced during
      cloning procedures, we compared the efficiency of development of parthenogenetic
      and cloned embryos made with DBA/2, C57BL/6, and (B6D2)F1 oocytes. Our results
      reveal significant differences in the ability of oocytes of different genetic
      backgrounds to support parthenogenetic development in different culture media.
      Additionally, our results reveal oocyte strain-dependent differences in the
      ability to support cloned embryo development beyond what can be accounted for on
      the basis of differences in parthenogenesis. Thus, the previously documented
      differences in oocyte-directed parental genome modification are accompanied in
      the same strains by differences in the ability of oocytes to modify somatic cell
      nuclei and support clonal development, raising the possibility that these oocyte
      functions may be mediated by related mechanisms. These results provide a genetic
      basis for further studies seeking to identify specific genes that determine
      oocyte phenotype, as well as genes that determine the success of nuclear
      reprogramming and clonal development.

PMID- 14681202
TI  - Protein kinase C and mitogen-activated protein kinase cascade in mouse cumulus
      cells: cross talk and effect on meiotic resumption of oocyte.
AB  - Protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) in cumulus
      cells are involved in FSH-induced meiotic resumption of cumulus-enclosed oocytes
      (CEOs), but their regulation and cross talk are unknown. The present experiments
      were designed to investigate 1) the possible involvement of MAPK cascade in PKC
      induced meiotic resumption; 2) the regulation of PKC on MAPK activity in FSH
      induced oocyte maturation; and 3) the pattern of PKC and MAPK function in induced
      meiotic resumption of mouse oocytes. PKC activators, phorbol 12-myristate 13
      acetate (PMA) and 1-oleoyl-2-acetyl-sn-glycerol (OAG), induced the meiotic
      resumption of CEOs and activation of MAPK in cumulus cells, whereas this effect
      could be abolished by PKC inhibitors, calphostin C and chelerythrine, or MEK
      inhibitor U0126. These results suggest that PKC might induce the meiotic
      reinitiation of CEOs by activating MAPK in cumulus cells. Both PKC inhibitors and
      U0126 inhibited the FSH-induced germinal vesicle breakdown (GVBD) of oocytes and
      MAPK activation in cumulus cells, suggesting that PKC and MAPK are involved in
      FSH-induced GVBD of mouse CEOs. Protein synthesis inhibitor cycloheximide (CHX)
      inhibited FSH- or PMA-induced oocyte meiotic resumption, but not the MAPK
      activation in cumulus cells. FSH and PKC activators induced the GVBD in denuded
      oocytes cocultured with cumulus cells in hypoxanthine (HX)-supplemented medium,
      and this effect could be reversed by U0126. Thus, when activated by FSH and PKC,
      MAPK may stimulate the synthesis of specific proteins in cumulus cells followed
      by secretion of an unknown positive factor that is capable of inducing GVBD in
      oocytes.

PMID- 14681203
TI  - Calcium homeostasis and contraction of the uterine artery: effect of pregnancy
      and chronic hypoxia.
AB  - The present study tested the hypothesis that chronic hypoxia alters pregnancy
      mediated adaptation of Ca2+ homeostasis and contractility in the uterine artery.
      Uterine arteries were isolated from nonpregnant and near-term pregnant ewes of
      normoxic control or high-altitude (3820 m) hypoxic (oxygen pressure in the blood
      [PaO2], 60 mm Hg) treatment for 110 days. Contractions and intracellular-free
      Ca2+ concentration ([Ca2+]i) were measured simultaneously in the same tissue. In
      normoxic animals, pregnancy increased norepinephrine (NE), but not 5-hydroxy
      thymide (5-HT) or KCl, contractile sensitivity in the uterine artery. Chronic
      hypoxia significantly attenuated NE-induced contractions in the pregnant, but not
      nonpregnant, uterine arteries. Similarly, 5-HT-mediated contractions of
      nonpregnant arteries were not changed. In the pregnant uterine artery, chronic
      hypoxia significantly increased NE-mediated Ca2+ mobilization, but decreased the
      Ca2+ sensitivity. In addition, hypoxia increased the calcium ionophore A23187
      induced relaxation in pregnant, but not nonpregnant, uterine arteries. However,
      the A23187-mediated reduction of [Ca2+]i was significantly impaired in hypoxic
      arteries. In contrast, hypoxia significantly increased the slope of the [Ca2+]i
      tension relationship of A23187-induced reductions in [Ca2+]i and tension in the
      pregnant uterine artery. The results suggest that the contractility of
      nonpregnant uterine artery is insensitive to moderate chronic hypoxia, but the
      adaptation of sympathetic tone that normally occurs in the uterine artery during
      pregnancy is inhibited by chronic hypoxia. In addition, changes in Ca2+
      sensitivity of myofilaments play a predominant role in the adaptation of uterine
      artery contractility to pregnancy and chronic hypoxia.

PMID- 14681204
TI  - Ataxia telangiectasia mutated expression and activation in the testis.
AB  - Ionizing radiation (IR) and consequent induction of DNA double-strand breaks
      (DSBs) causes activation of the protein ataxia telangiectasia mutated (ATM).
      Normally, ATM is present as inactive dimers; however, in response to DSBs, the
      ATM dimer partners cross-phosphorylate each other on serine 1981, and kinase
      active ATM monomers are subsequently released. We have studied the presence of
      both nonphosphorylated as well as active serine 1981 phosphorylated ATM (pS1981
      ATM) in the mouse testis. In the nonirradiated testis, ATM was present in
      spermatogonia and spermatocytes until stage VII of the cycle of the seminiferous
      epithelium, whereas pS1981-ATM was found only to be present in the sex body of
      pachytene spermatocytes. In response to IR, ATM became activated by pS1981 cross
      phosphorylation in spermatogonia and Sertoli cells. Despite the occurrence of
      endogenous programmed DSBs during the first meiotic prophase and the presence of
      ATM in both spermatogonia and spermatocytes, pS1981 phosphorylated ATM did not
      appear in spermatocytes after treatment with IR. These results show that
      spermatogonial ATM and ATM in the spermatocytes are differentially regulated. In
      the mitotically dividing spermatogonia, ATM is activated by cross
      phosphorylation, whereas during meiosis nonphosphorylated ATM or differently
      phosphorylated ATM is already active. ATM has been shown to be present at the
      synapsed axes of the meiotic chromosomes, and in the ATM knock-out mice
      spermatogenesis stops at pachytene stage IV of the seminiferous epithelium,
      indicating that indeed nonphosphorylated ATM is functional during meiosis.
      Additionally, ATM is constitutively phosphorylated in the sex body where its
      continued presence remains an enigma.

PMID- 14681205
TI  - The c-myc and PyMT oncogenes induce different tumor types in a somatic mouse
      model for pancreatic cancer.
AB  - We have generated a mouse model for pancreatic cancer through the somatic
      delivery of oncogene-bearing avian retroviruses to mice that express TVA, the
      receptor for avian leukosis sarcoma virus subgroup A (ALSV-A), under the control
      of the elastase promoter. Delivery of ALSV-A-based RCAS vectors encoding either
      mouse polyoma virus middle T antigen (PyMT) or c-Myc to elastase-tv-a transgenic,
      Ink4a/Arf null mice induced the formation of pancreatic tumors. RCAS-PyMT induced
      pancreatic tumors with the histologic features of acinar or ductal carcinomas.
      The induced pancreatic lesions express Pdx1, a marker for pancreas progenitor
      cells, and many tumors express markers for both exocrine and endocrine cell
      lineages, suggesting that the tumors may be derived from progenitor cells. In
      contrast, RCAS-c-myc induced endocrine tumors exclusively, as determined by
      histology and detection of differentiation markers. Thus, specific oncogenes can
      induce the formation of different pancreatic tumor types in a single transgenic
      line, most likely from one or more types of multipotential progenitor cells. Our
      model appears to be useful for elucidating the genetic alterations, target cells,
      and signaling pathways that are important in the genesis of different types of
      pancreatic cancer.

PMID- 14681206
TI  - SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein
      phosphatase.
AB  - Eukaryotic cells respond to DNA damage and stalled replication forks by
      activating protein kinase-mediated signaling pathways that promote cell cycle
      arrest and DNA repair. A central target of the cell cycle arrest program is the
      Cdc25A protein phosphatase. Cdc25A is required for S-phase entry and
      dephosphorylates tyrosine-15 phosphorylated Cdk1 (Cdc2) and Cdk2, positive
      regulators of cell division. Cdc25A is unstable during S-phase and is degraded
      through the ubiquitin-proteasome pathway, but its turnover is enhanced in
      response to DNA damage. Although basal and DNA-damage-induced turnover depends on
      the ATM-Chk2 and ATR-Chk1 pathways, how these kinases engage the ubiquitin ligase
      machinery is unknown. Here, we demonstrate a requirement for SCFbeta-TRCP in
      Cdc25A turnover during an unperturbed cell cycle and in response to DNA damage.
      Depletion of beta-TRCP stabilizes Cdc25A, leading to hyperactive Cdk2 activity.
      SCFbeta-TRCP promotes Chk1-dependent Cdc25A ubiquitination in vitro, and this
      involves serine 76, a known Chk1 phosphorylation site. However, recognition of
      Cdc25A by beta-TRCP occurs via a noncanonical phosphodegron in Cdc25A containing
      phosphoserine 79 and phosphoserine 82, sites that are not targeted by Chk1. These
      data indicate that Cdc25A turnover is more complex than previously appreciated
      and suggest roles for an additional kinase(s) in Chk1-dependent Cdc25A turnover.

PMID- 14681207
TI  - Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic
      pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma ranks among the most lethal of human
      malignancies. Here, we assess the cooperative interactions of two signature
      mutations in mice engineered to sustain pancreas-specific Cre-mediated activation
      of a mutant Kras allele (KrasG12D) and deletion of a conditional Ink4a/Arf tumor
      suppressor allele. The phenotypic impact of KrasG12D alone was limited primarily
      to the development of focal premalignant ductal lesions, termed pancreatic
      intraepithelial neoplasias (PanINs), whereas the sole inactivation of Ink4a/Arf
      failed to produce any neoplastic lesions in the pancreas. In combination,
      KrasG12D expression and Ink4a/Arf deficiency resulted in an earlier appearance of
      PanIN lesions and these neoplasms progressed rapidly to highly invasive and
      metastatic cancers, resulting in death in all cases by 11 weeks. The evolution of
      these tumors bears striking resemblance to the human disease, possessing a
      proliferative stromal component and ductal lesions with a propensity to advance
      to a poorly differentiated state. These findings in the mouse provide
      experimental support for the widely accepted model of human pancreatic
      adenocarcinoma in which activated KRAS serves to initiate PanIN lesions, and the
      INK4A/ARF tumor suppressors function to constrain the malignant conversion of
      these PanIN lesions into lethal ductal adenocarcinoma. This faithful mouse model
      may permit the systematic analysis of genetic lesions implicated in the human
      disease and serve as a platform for the identification of early disease markers
      and for the efficient testing of novel therapies.

PMID- 14681208
TI  - Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs.
AB  - MicroRNAs (miRNAs) are initially expressed as long transcripts that are processed
      in the nucleus to yield approximately 65-nucleotide (nt) RNA hairpin
      intermediates, termed pre-miRNAs, that are exported to the cytoplasm for
      additional processing to yield mature, approximately 22-nt miRNAs. Here, we
      demonstrate that human pre-miRNA nuclear export, and miRNA function, are
      dependent on Exportin-5. Exportin-5 can bind pre-miRNAs specifically in vitro,
      but only in the presence of the Ran-GTP cofactor. Short hairpin RNAs, artificial
      pre-miRNA analogs used to express small interfering RNAs, also depend on Exportin
      5 for nuclear export. Together, these findings define an additional cellular
      cofactor required for miRNA biogenesis and function.

PMID- 14681209
TI  - Nurr1-RXR heterodimers mediate RXR ligand-induced signaling in neuronal cells.
AB  - The retinoid X receptor (RXR) is essential as a common heterodimerization partner
      of several nuclear receptors (NRs). However, its function as a bona fide receptor
      for endogenous ligands has remained poorly understood. Such a role would depend
      on the existence of RXR activating ligands in vivo and on the ability of such
      ligands to influence relevant biological functions. Here we demonstrate the
      presence of endogenous RXR ligands in the embryonic central nervous system (CNS)
      and show that they can activate heterodimers formed between RXR and the orphan NR
      Nurr1 in vivo. Moreover, RXR ligands increase the number of surviving
      dopaminergic cells and other neurons in a process mediated by Nurr1-RXR
      heterodimers. These results provide evidence for a role of Nurr1 as a ligand
      independent partner of RXR in its function as a bona fide ligand-activated NR.
      Finally, our findings identify RXR-Nurr1 heterodimers as a potential target in
      the treatment of neurodegenerative disease.

PMID- 14681210
TI  - Stabilization of stalled DNA replication forks by the BRCA2 breast cancer
      susceptibility protein.
AB  - How dividing mammalian cells overcome blocks to DNA replication by DNA damage,
      depleted nucleotide pools, or template-bound proteins is unclear. Here, we show
      that the response to blocked replication requires BRCA2, a suppressor of human
      breast cancer. By using two-dimensional gel electrophoresis, we demonstrate that
      Y-shaped DNA junctions at stalled replication forks disappear during genome-wide
      replication arrest in BRCA2-deficient cells, accompanied by double-strand DNA
      breakage. But activation of the replication checkpoint kinase Chk2 is unaffected,
      defining an unexpected function for BRCA2 in stabilizing DNA structures at
      stalled forks. We propose that in BRCA2 deficiency and related chromosomal
      instability diseases, the breakdown of replication forks, which arrest or pause
      during normal cell growth, triggers spontaneous DNA breakage, leading to
      mutability and cancer predisposition.

PMID- 14681211
TI  - A physiological role for the posttranslational cleavage of the thyrotropin
      receptor?

PMID- 14681212
TI  - The skinny on body weight regulation: the role of retinoid signaling in
      photoperiod-mediated weight loss.

PMID- 14681214
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 14681216
TI  - WNK1 activates ERK5 by an MEKK2/3-dependent mechanism.
AB  - WNK1 belongs to a unique protein kinase family that lacks the catalytic lysine in
      its normal position. Mutations in human WNK1 and WNK4 have been implicated in
      causing a familial form of hypertension. Here we report that overexpression of
      WNK1 led to increased activity of cotransfected ERK5 in HEK293 cells. ERK5
      activation was blocked by the MEK5 inhibitor U0126 and expression of a dominant
      negative MEK5 mutant. Expression of dominant negative mutants of MEKK2 and MEKK3
      also blocked activation of ERK5 by WNK1. Moreover, both MEKK2 and MEKK3
      coimmunoprecipitated with endogenous WNK1 from cell lysates. WNK1 phosphorylated
      both MEKK2 and -3 in vitro, and MEKK3 was activated by WNK1 in 293 cells.
      Finally, ERK5 activation by epidermal growth factor was attenuated by suppression
      of WNK1 expression using small interfering RNA. Taken together, these results
      place WNK1 in the ERK5 MAP kinase pathway upstream of MEKK2/3.

PMID- 14681217
TI  - Involvement of transmembrane domain interactions in signal transduction by
      alpha/beta integrins.
AB  - The alpha and beta subunits of alpha/beta heterodimeric integrins function
      together to bind ligands in the extracellular region and transduce signals across
      cellular membranes. A possible function for the transmembrane regions in integrin
      signaling has been proposed from structural and computational data. We have
      analyzed the capacity of the integrin alpha(2), alpha(IIb), alpha(4), beta(1),
      beta(3), and beta(7) transmembrane domains to form homodimers and/or
      heterodimers. Our data suggest that the integrin transmembrane helices can help
      to stabilize heterodimeric integrins but that the interactions do not
      specifically associate particular pairs of alpha and beta subunits; rather, the
      alpha/beta subunit interaction constrains the extramembranous domains,
      facilitating signal transduction by a promiscuous transmembrane helix-helix
      association.

PMID- 14681218
TI  - Developmental cell death in dictyostelium does not require paracaspase.
AB  - Apoptotic cell death often requires caspases. Caspases are part of a family of
      related molecules including also paracaspases and metacaspases. Are molecules of
      this family generally involved in cell death? More specifically, do non-apoptotic
      caspase-independent types of cell death require paracaspases or metacaspases?
      Dictyostelium discoideum lends itself well to answering these questions because
      1) it undergoes non-apoptotic developmental cell death of a vacuolar autophagic
      type and 2) it bears neither caspase nor metacaspase genes and apparently only
      one paracaspase gene. This only paracaspase gene can be inactivated by homologous
      recombination. Paracaspase-null clones were thus obtained in each of four
      distinct Dictyostelium strains. These clones were tested in two systems,
      developmental stalk cell death in vivo and vacuolar autophagic cell death in a
      monolayer system mimicking developmental cell death. Compared with parent cells,
      all of the paracaspase-null cells showed unaltered cell death in both test
      systems. In addition, paracaspase inactivation led to no alteration in
      development or interaction with a range of bacteria. Thus, in Dictyostelium,
      vacuolar programmed cell death in development and in a monolayer model in vitro
      would seem not to require paracaspase. To our knowledge, this is the first
      instance of developmental programmed cell death shown to be independent of any
      caspase, paracaspase or metacaspase. These results have implications as to the
      relationship in evolution between cell death and the caspase family.

PMID- 14681219
TI  - Activation of type I phosphatidylinositol 4-phosphate 5-kinase isoforms by the
      Rho GTPases, RhoA, Rac1, and Cdc42.
AB  - Type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) catalyzes the formation
      of the phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP(2)), which is
      implicated in many cellular processes. The Rho GTPases, RhoA and Rac1, have been
      shown previously to activate PIP5K and to bind PIP5K. Three type I PIP5K isoforms
      (Ialpha,Ibeta, and Igamma) have been identified; however, it is unclear whether
      these isoforms are differentially or even sequentially regulated by Rho GTPases.
      Here we show that RhoA and Rac1, as well as Cdc42, but not the Ras-like GTPases,
      RalA and Rap1A, markedly stimulate PIP(2) synthesis by all three PIP5K isoforms
      expressed in human embryonic kidney 293 cells, both in vitro and in vivo. RhoA
      stimulated PIP(2) synthesis by the PIP5K isoforms was mediated by the RhoA
      effector, Rho-kinase. Stimulation of PIP5K isoforms by Rac1 and Cdc42 was
      apparently independent of and additive with RhoA- and Rho-kinase, as shown by
      studies with C3 transferase and Rho-kinase mutants. RhoA, and to a lesser extent
      Rac1, but not Cdc42, interacted in a nucleotide-independent form with all three
      PIP5K isoforms. Binding of PIP5K isoforms to GTP-bound, but not GDP-bound, RhoA
      could be displaced by Rho-kinase, suggesting a direct and constitutive PIP5K-Rho
      GTPase binding, which, however, does not trigger PIP5K activation. In summary,
      our findings indicate that synthesis of PIP(2) by the three PIP5K isoforms is
      controlled by RhoA, acting via Rho-kinase, as well as Rac1 and Cdc42, implicating
      that regulation of PIP(2) synthesis has a central position in signaling by these
      three Rho GTPases.

PMID- 14681220
TI  - Locking the beta3 integrin I-like domain into high and low affinity conformations
      with disulfides.
AB  - Although integrin alpha subunit I domains exist in multiple conformations, it is
      controversial whether integrin beta subunit I-like domains undergo structurally
      analogous movements of the alpha7-helix that are linked to affinity for ligand.
      Disulfide bonds were introduced into the beta(3) integrin I-like domain to lock
      its beta6-alpha7 loop and alpha7-helix in two distinct conformations. Soluble
      ligand binding, ligand mimetic mAb binding and cell adhesion studies showed that
      disulfide-bonded receptor alpha(IIb)beta(3)(T329C/A347C) was locked in a low
      affinity state, and dithiothreitol treatment restored the capability of being
      activated to high affinity binding; by contrast, disulfide-bonded
      alpha(IIb)beta(3)(V332C/M335C) was locked in a high affinity state. The results
      suggest that activation of the beta subunit I-like domain is analogous to that of
      the alpha subunit I domain, i.e. that axial movement in the C-terminal direction
      of the alpha7-helix is linked to rearrangement of the I-like domain metal ion
      dependent adhesion site into a high affinity conformation.

PMID- 14681221
TI  - p300 regulates the synergy of steroidogenic factor-1 and early growth response-1
      in activating luteinizing hormone-beta subunit gene.
AB  - Tight regulation of luteinizing hormone-beta subunit (LHbeta) expression is
      critical for differentiation and maturation of mammalian sexual organs and
      reproductive function. Two transcription factors, steroidogenic factor-1 (SF-1)
      and early growth response-1 (Egr-1), play a central role in activating LHbeta
      promoter, and the synergy between these two factors is essential in mediating
      gonadotropin-releasing hormone stimulation of LHbeta promoter. Here we
      demonstrate that the transcriptional co-activator p300 regulates this synergy.
      Overexpression of p300 results in strong stimulation of LHbeta promoter but only
      in the presence of both SF-1 and Egr-1, and not in the presence of other Egr
      proteins. Mutation of the binding sites for either SF-1 or Egr-1 completely
      abolishes the synergy between these two factors, as well as the influence of
      p300. Importantly, LHbeta promoter is precipitated using p300 antibodies in a
      chromatin immunoprecipitation assay with LbetaT2 gonadotropes, and this effect is
      enhanced by gonadotropin-releasing hormone. The influence of p300 on LHbeta
      promoter is potentiated by steroid receptor co-activator, as well as by E1A
      proteins, and attenuated by Smad nuclear interacting protein 1. Taken together,
      these results suggest that p300 is recruited to LHbeta promoter where it
      coordinates the functional synergy between SF-1 and Egr-1.

PMID- 14681222
TI  - Neuronal-specific synthesis and glycosylation of tenascin-R.
AB  - Tenascin-R (TN-R) is a member of the tenascin family of multidomain matrix
      glycoproteins that is expressed exclusively in the central nervous system by
      oligodendrocytes and small neurons during postnatal development and in the adult.
      TN-R contributes to the regulation of axon extension and regeneration, neurite
      formation and synaptogenesis, and neuronal growth and migration. TN-R can be
      modified with three distinct sulfated oligosaccharide structures: HNK-1 (SO(4)-3
      GlcUAbeta1,3Galbeta1,4GlcNAc), GalNAc-4-SO(4), and chondroitin sulfate. We have
      determined that TN-R expressed in dendrite-rich regions of the rat cerebellum,
      hippocampus, and cerebral cortex is one of the major matrix glycoproteins that
      bears N-linked carbohydrates terminating with beta1,4-linked GalNAc-4-SO(4). The
      syntheses of these unique sulfated structures on TN-R are differentially
      regulated. Levels of HNK-1 on TN-R rise and fall in parallel to the levels of TN
      R during postnatal development of the cerebellum. In contrast, levels of GalNAc-4
      SO(4) are regulated independently from those of TN-R, rising late in cerebellar
      development and continuing into adulthood. As a result, the pattern of TN-R
      modification with distinct sulfated carbohydrate structures changes dramatically
      over the course of postnatal cerebellar development in the rat. Because TN-R
      interacts with a number of different matrix components and, depending on the
      circumstances, can either activate or inhibit neurite outgrowth, the highly
      regulated addition of these unique sulfated structures may modulate the adhesive
      properties of TN-R over the course of development and during synapse maintenance.
      In addition, the 160-kDa form of TN-R is particularly enriched for terminal
      GalNAc-4-SO(4) later in development and in the adult, suggesting additional
      levels of regulation.

PMID- 14681223
TI  - Differential mode of regulation of the checkpoint kinases CHK1 and CHK2 by their
      regulatory domains.
AB  - CHK1 and CHK2 are key mediators that link the machineries that monitor DNA
      integrity to components of the cell cycle engine. Despite the similarity and
      potential redundancy in their functions, CHK1 and CHK2 are unrelated protein
      kinases, each having a distinctive regulatory domain. Here we compare how the
      regulatory domains of human CHK1 and CHK2 modulate the respective kinase
      activities. Recombinant CHK1 has only low basal activity when expressed in
      cultured cells. Surprisingly, disruption of the C-terminal regulatory domain
      activates CHK1 even in the absence of stress. Unlike the full-length protein, C
      terminally truncated CHK1 displays autophosphorylation, phosphorylates CDC25C on
      Ser(216), and delays cell cycle progression. Intriguingly, enzymatic activity
      decreases when the entire regulatory domain is removed, suggesting that the
      regulatory domain contains both inhibitory and stimulatory elements. Conversely,
      the kinase domain suppresses Ser(345) phosphorylation, a major ATM/ATR
      phosphorylation site in the regulatory domain. In marked contrast, CHK2 expressed
      in either mammalian cells or in bacteria is already active as a kinase against
      itself and CDC25C and can delay cell cycle progression. Unlike CHK1, disruption
      of the regulatory domain of CHK2 abolishes its kinase activity. Moreover, the
      regulatory domain of CHK2, but not that of CHK1, can oligomerize. Finally, CHK1
      but not CHK2 is phosphorylated during the spindle assembly checkpoint, which
      correlates with the inhibition of the kinase. The mitotic phosphorylation of CHK1
      requires the regulatory domain, does not involve Ser(345), and is independent on
      ATM. Collectively, these data reveal the very different mode of regulation
      between CHK1 and CHK2.

PMID- 14681224
TI  - The p18 truncated form of Bax behaves like a Bcl-2 homology domain 3-only
      protein.
AB  - p21(Bax) is a pro-apoptotic member of the Bcl-2 family and is converted by
      calpain into a truncated form called p18(Bax). This proteolysis enhanced the
      apoptogenic properties of Bax by a mechanism not yet elucidated. We have shown
      recently that the first alpha helix (Halpha1) of p21(Bax) contained a
      mitochondrial addressing sequence, which appeared to be necessary for p21(Bax)
      induced apoptosis (Cartron, P. F., Priault, M., Oliver, L., Meflah, K., Manon,
      S., and Vallette, F. M. (2003) J. Biol. Chem. 278, 11633-11641). This feature is
      in contradiction with the high apoptogenic profile of p18(Bax), because the
      Halpha1 is lost during the calpain cleavage of p21(Bax). We investigated the role
      of p18(Bax) in apoptosis and found that its activity required the presence of
      p21(Bax). In addition, p18(Bax) exhibited a higher affinity for Bcl-Xl than
      p21(Bax) did, a property that seems to be essential for the fulfillment of its
      pro-apoptotic role. In conclusion, calpain proteolysis converts the multi-domain
      p21(Bax) into a Bcl-2 homology 3-like protein capable of overcoming the
      inhibition of apoptosis due to Bcl-Xl.

PMID- 14681225
TI  - Extracellular signal-regulated kinases 1/2 are serum-stimulated "Bim(EL) kinases"
      that bind to the BH3-only protein Bim(EL) causing its phosphorylation and
      turnover.
AB  - Bim, a "BH3-only" protein, is expressed de novo following withdrawal of serum
      survival factors and promotes cell death. We have shown previously that
      activation of the ERK1/2 pathway promotes phosphorylation of Bim(EL), targeting
      it for degradation via the proteasome. However, the nature of the kinase
      responsible for Bim(EL) phosphorylation remained unclear. We now show that
      Bim(EL) is phosphorylated on at least three sites in response to activation of
      the ERK1/2 pathway. By using the peptidylprolyl isomerase, Pin1, as a probe for
      proline-directed phosphorylation, we show that ERK1/2-dependent phosphorylation
      of Bim(EL) occurs at (S/T)P motifs. ERK1/2 phosphorylates Bim(EL), but not Bim(S)
      or Bim(L), in vitro, and mutation of Ser(65) to alanine blocks the
      phosphorylation of Bim(EL) by ERK1/2 in vitro and in vivo and prevents the
      degradation of the protein following activation of the ERK1/2 pathway. We also
      find that ERK1/2, but not JNK, can physically associate with GST-Bim(EL), but not
      GST-Bim(L) or GST-Bim(S), in vitro. ERK1/2 also binds to full-length Bim(EL) in
      vivo, and we have localized a potential ERK1/2 "docking domain" lying within a 27
      amino acid stretch of the Bim(EL) protein. Our findings provide new insights into
      the post-translational regulation of Bim(EL) and the role of the ERK1/2 pathway
      in cell survival signaling.

PMID- 14681226
TI  - The effect of RNA interference Down-regulation of RNA editing 3'-terminal
      uridylyl transferase (TUTase) 1 on mitochondrial de novo protein synthesis and
      stability of respiratory complexes in Trypanosoma brucei.
AB  - Inhibition of RNA editing by down-regulation of expression of the mitochondrial
      RNA editing TUTase 1 by RNA interference had profound effects on kinetoplast
      biogenesis in Trypanosoma brucei procyclic cells. De novo synthesis of the
      apocytochrome b and cytochrome oxidase subunit I proteins was no longer
      detectable after 3 days of RNAi. The effect on protein synthesis correlated with
      a decline in the levels of the assembled mitochondrial respiratory complexes III
      and IV, and also cyanide-sensitive oxygen uptake. The steady-state levels of
      nuclear-encoded subunits of complexes III and IV were also significantly
      decreased. Because the levels of the corresponding mRNAs were not affected, the
      observed effect was likely due to an increased turnover of these imported
      mitochondrial proteins. This induced protein degradation was selective for
      components of complexes III and IV, because little effect was observed on
      components of the F(1).F(0)-ATPase complex and on several other mitochondrial
      proteins.

PMID- 14681227
TI  - Structure of the catalytic fragment of translation initiation factor 2B and
      identification of a critically important catalytic residue.
AB  - Eukaryotic initiation factor (eIF) 2B catalyzes the nucleotide activation of eIF2
      to its active GTP-bound state. The exchange activity has been mapped to the C
      terminus of the eIF2Bepsilon subunit. We have determined the crystal structure of
      residues 544-704 from yeast eIF2Bepsilon at 2.3-A resolution, and this fragment
      is an all-helical protein built around the conserved aromatic acidic (AA) boxes
      also found in eIF4G and eIF5. The eight helices are organized in a manner similar
      to HEAT repeats. The molecule is highly asymmetric with respect to surface charge
      and conservation. One area in the N terminus is proposed to be directly involved
      in catalysis. In agreement with this hypothesis, mutation of glutamate 569 is
      shown to be lethal. An acidic belt and a second area in the C terminus containing
      residues from the AA boxes are important for binding to eIF2. Two mutations
      causing the fatal human genetic disease leukoencephalopathy with vanishing white
      matter are buried and appear to disrupt the structural integrity of the catalytic
      domain rather than interfering directly with catalysis or binding of eIF2.

PMID- 14681228
TI  - Metformin-stimulated mannose transport in dermal fibroblasts.
AB  - The biguanide drug metformin stimulates AMP-activated protein kinase, a master
      regulator of cellular energy metabolism, and has antihyperglycemic activity due
      to attenuation of gluconeogenesis in hepatocytes and 2-fold stimulation of
      glucose transport by skeletal muscle. Here we identify a metformin-stimulated d
      mannose transport (MSMT) activity in dermal fibroblasts. MSMT increased mannose
      uptake 1.8-fold and had greater affinity for mannose than basal mannose transport
      activity. It was attributed to robust stimulation of a transporter expressed
      weakly in untreated cells. MSMT was not explained by greater glucose transporter
      activity because metformin unexpectedly decreased transport of 2-deoxy-d-glucose
      and 3-O-methyl-d-glucose by fibroblasts. Effective inhibitors of MSMT retained
      specificity for the 3-, 4-, and 6-OH groups of the mannose ring but not the 2-OH
      group. Thus, MSMT could be strongly inhibited by glucose and 2-deoxy-d-glucose
      even though the latter was not a good transport substrate. MSMT was significant
      because in the presence of 2.5 microm mannose, metformin corrected experimentally
      induced deficiencies in the synthesis of glucose(3)mannose(9)GlcNAc(2)-P-P
      dolichol and N-linked glycosylation. MSMT was also identified in congenital
      disorder of glycosylation types Ia and Ib fibroblasts, and metformin acted
      synergistically with 100 microm mannose to correct lipid-linked oligosaccharide
      synthesis and N-glycosylation in the Ia cells. In conclusion, metformin activates
      a novel fibroblast mannose-selective transport system. This suggests that AMP
      activated protein kinase may be a regulator of mannose metabolism and implies a
      therapy for congenital disorders of glycosylation-Ia.

PMID- 14681229
TI  - Role of iron (II)-2-oxoglutarate-dependent dioxygenases in the generation of
      hypoxia-induced phosphatidic acid through HIF-1/2 and von Hippel-Lindau
      independent mechanisms.
AB  - Hypoxia-inducible factors (HIF-1/HIF-2) govern the expression of critical genes
      for cellular adaptation to low oxygen tensions. We have previously reported that
      the intracellular level of phosphatidic acid (PA) rises in response to hypoxia
      (1% O(2)). In this report, we have explored whether components of the canonical
      HIF/von Hippel-Lindau (VHL) pathway are involved in the induction of PA. We found
      that hypoxia induces PA in a cell line constitutively expressing a stable version
      of HIF-1alpha. PA induction was also found in HIF-1alpha- and 2alpha-negative CHO
      Ka13 cells, as well as in HIF-beta-negative HepaC4 cells. These data indicate
      that HIF activity is neither sufficient nor necessary for oxygen-dependent PA
      accumulation. PA generation was also detected in cells deficient for the tumor
      suppressor VHL, indicating that the presence of VHL was not required for the
      induction of PA. Here we show that PA accumulation also occurs at moderate
      hypoxia (5% O(2)), although to a lesser extent to that seen at 1% O(2), revealing
      that PA is induced at the same hypoxia range required to activate HIF-1. Prolyl
      hydroxylases (PHD) and asparaginyl hydroxylase (FIH) belong to the iron (II) and
      2-oxoglutarate-dependent dioxygenase family and have been proposed as oxygen
      sensors involved in the regulation of HIFs. Chemical inhibition of these
      activities by treatment with iron chelators or 2-oxoglutarate analogs also
      results in a marked PA accumulation similar to that observed in hypoxia. Together
      these data show that PA accumulation in response to hypoxia is both HIF-1/2- and
      VHL-independent and indicate a role of iron (II)-2-oxoglutarate-dependent
      dioxygenases in the oxygen-sensing mechanisms involved in hypoxia-driven
      phospholipid regulation.

PMID- 14681230
TI  - Identification of caveolin-1-interacting sites in neuronal nitric-oxide synthase.
      Molecular mechanism for inhibition of NO formation.
AB  - Caveolin is known to down-regulate both neuronal (nNOS) and endothelial nitric
      oxide synthase (eNOS). In the present study, direct interactions of recombinant
      caveolin-1 with both the oxygenase and reductase domains of nNOS were
      demonstrated using in vitro binding assays. To elucidate the mechanism of nNOS
      regulation by caveolin, we examined the effects of a caveolin-1 scaffolding
      domain peptide (CaV1p1; residues (82-101)) on the catalytic activities of wild
      type and mutant nNOSs. CaV1p1 inhibited NO formation activity and NADPH oxidation
      of wild-type nNOS in a dose-dependent manner with an IC(50) value of 1.8 microM.
      Mutations of Phe(584) and Trp(587) within a caveolin binding consensus motif of
      the oxygenase domain did not result in the loss of CaV1p1 inhibition, indicating
      that an alternate region of nNOS mediates inhibition by caveolin. The addition of
      CaV1p1 also inhibited more than 90% of the cytochrome c reductase activity in the
      isolated reductase domain with or without the calmodulin (CaM) binding site,
      whereas CaV1p1 inhibited ferricyanide reductase activity by only 50%. These
      results suggest that there are significant differences in the mechanism of
      inhibition by caveolin for nNOS as compared with those previously reported for
      eNOS. Further analysis of the interaction through the use of several reductase
      domain deletion mutants revealed that the FMN domain was essential for successful
      interaction between caveolin-1 and nNOS reductase. We also examined the effects
      of CaV1p1 on an autoinhibitory domain deletion mutant (Delta40) and a C-terminal
      truncation mutant (DeltaC33), both of which are able to form NO in the absence of
      CaM, unlike the wild-type enzyme. Interestingly, CaV1p1 inhibited CaM-dependent,
      but not CaM-independent, NO formation activities of both Delta40 and DeltaC33,
      suggesting that CaV1p1 inhibits interdomain electron transfer induced by CaM from
      the reductase domain to the oxygenase domain.

PMID- 14681231
TI  - Tumor necrosis factor alpha inhibits cyclin A expression and retinoblastoma
      hyperphosphorylation triggered by insulin-like growth factor-I induction of new
      E2F-1 synthesis.
AB  - Cyclin A is required for cell cycle S phase entry, and its overexpression
      contributes to tumorigenesis. Release of pre-existing E2Fs from inactive
      complexes of E2F and hypophosphorylated retinoblastoma (RB) is the prevailing
      dogma for E2F transcriptional activation of target genes such as cyclin A. Here
      we explored the hypothesis that new synthesis of E2F-1 is required for insulin
      like growth factor-I (IGF-I) to induce cyclin A accumulation and RB
      hyperphosphorylation, events that are targeted by tumor necrosis factor alpha
      (TNFalpha) to arrest cell cycle progression. We first established that IGF-I
      increases expression of cyclin A, causes hyperphosphorylation of RB, and augments
      the mass of E2F-1 in a time-dependent manner. As expected, E2F-1 small
      interfering RNA blocks the ability of IGF-I to increase synthesis of E2F-1. Most
      important, this E2F-1 small interfering RNA also blocks the ability of IGF-I to
      increase cyclin A accumulation and to hyperphosphorylate RB. We next established
      that TNFalpha dose-dependently inhibits IGF-I-induced phosphorylation of both RB
      and histone H1 by cyclin A-dependent cyclin-dependent kinases. Cyclin-dependent
      kinase 2 (Cdk2) mediates this suppression because co-immunoprecipitation
      experiments revealed that TNFalpha reduces the amount of IGF-I-induced cyclin A
      that binds Cdk2, leading to a reduction in Cdk2 enzymatic activity. TNFalpha
      antagonizes the ability of IGF-I to increase mass of both E2F-1 and cyclin A but
      not cyclin E or D1. The cytostatic property of TNFalpha is also shown by its
      ability to block IGF-I-stimulated luciferase activity of a cyclin A promoter
      reporter. Deletion of an E2F recognition site from this reporter eliminates the
      regulatory effects of both IGF-I and TNFalpha on cyclin A transcription,
      indicating the essential role of E2F-1 in mediating their cross-talk.
      Collectively, these results establish that TNFalpha targets IGF-I-induced E2F-1
      synthesis, leading to inhibition of the subsequent accumulation in cyclin A,
      formation of cyclin A-Cdk2 complexes, hyperphosphorylation of RB, and cell cycle
      arrest.

PMID- 14681232
TI  - Feed-forward regulation of bile acid detoxification by CYP3A4: studies in
      humanized transgenic mice.
AB  - Bile acids are potentially toxic end products of cholesterol metabolism and their
      concentrations must be tightly regulated. Homeostasis is maintained by both feed
      forward regulation and feedback regulation. We used humanized transgenic mice
      incorporating 13 kb of the 5' regulatory flanking sequence of CYP3A4 linked to a
      lacZ reporter gene to explore the in vivo relationship between bile acids and
      physiological adaptive CYP3A gene regulation in acute cholestasis after bile duct
      ligation (BDL). Male transgenic mice were subjected to BDL or sham surgery prior
      to sacrifice on days 3, 6, and 10, and others were injected with intraperitoneal
      lithocholic acid (LCA) or vehicle alone. BDL resulted in marked hepatic
      activation of the CYP3A4/lacZ transgene in pericentral hepatocytes, with an 80
      fold increase in transgene activation by day 10. Individual bile acids were
      quantified by liquid chromatography/mass spectrometry. Serum 6beta-hydroxylated
      bile acids were increased following BDL, confirming the physiological relevance
      of endogenous Cyp3a induction to bile acid detoxification. Although
      concentrations of conjugated primary bile acids increased after BDL, there was no
      increase in LCA, a putative PXR ligand, indicating that this cannot be the only
      endogenous bile acid mediating this protective response. Moreover, in LCA-treated
      animals, 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside staining showed
      hepatic activation of the CYP3A4 transgene only on the liver capsular surface,
      and minimal parenchymal induction, despite significant liver injury. This study
      demonstrates that CYP3A up-regulation is a significant in vivo adaptive response
      to cholestasis. However, this up-regulation is not dependent on increases in
      circulating LCA and the role of other bile acids as regulatory molecules requires
      further exploration.

PMID- 14681233
TI  - Laminin alpha2 is essential for odontoblast differentiation regulating dentin
      sialoprotein expression.
AB  - Laminin alpha2 is subunit of laminin-2 (alpha2beta1gamma1), which is a major
      component of the muscle basement membrane. Although the laminin alpha2 chain is
      expressed in the early stage of dental mesenchyme development and localized in
      the tooth germ basement membrane, its expression pattern in the late stage of
      tooth germ development and molecular roles are not clearly understood. We
      analyzed the role of laminin alpha2 in tooth development by using targeted mice
      with a disrupted lama2 gene. Laminin alpha2 is expressed in dental mesenchymal
      cells, especially in odontoblasts and during the maturation stage of ameloblasts,
      but not in the pre-secretory or secretory stages of ameloblasts. Lama2 mutant
      mice have thin dentin and a widely opened dentinal tube, as compared with wild
      type and heterozygote mice, which is similar to the phenotype of dentinogenesis
      imperfecta. During dentin formation, the expression of dentin sialoprotein, a
      marker of odontoblast differentiation, was found to be decreased in odontoblasts
      from mutant mice. Furthermore, in primary cultures of dental mesenchymal cells,
      dentin matrix protein, and dentin sialophosphoprotein, mRNA expression was
      increased in laminin-2 coated dishes but not in those coated with other matrices,
      fibronectin, or type I collagen. Our results suggest that laminin alpha2 is
      essential for odontoblast differentiation and regulates the expression of dentin
      matrix proteins.

PMID- 14681234
TI  - Estrogen decreases zinc transporter 3 expression and synaptic vesicle zinc levels
      in mouse brain.
AB  - Previous studies suggest that female sex hormones modulate synaptic zinc levels,
      which may influence amyloid plaque formation and Alzheimer's disease progression.
      We examined the effects of ovariectomy and estrogen supplement on the levels of
      synaptic zinc and zinc transporter protein Znt3 in the brain. Ovariectomy was
      performed on 5-month-old mice, and 2 weeks later, pellets containing vehicle, low
      (0.18 mg/pellet), or high dose (0.72 mg) 17beta-estradiol were implanted. After 4
      weeks, animals were decapitated, and blood and brain were collected for analysis.
      Blood analysis indicated that estrogen implants altered plasma estrogen levels in
      a dose-dependent manner. Analysis of brain tissue showed that ovariectomy raised
      hippocampal synaptic vesicle zinc levels, whereas estrogen replacement lowered
      these zinc levels. Western blots revealed that Znt3 levels in the brain were
      modulated in parallel with synaptic zinc levels, whereas no change was detected
      in the levels of Znt3 mRNA, as determined by Northern blot and reverse
      transcriptase-PCR analysis. However, mRNA levels of the delta subunit of adaptor
      protein complex (AP)-3, which modulates the level of Znt3 levels, were altered by
      estrogen depletion or replacement. These data demonstrate that estrogen alters
      the levels of Znt3 and synaptic vesicle zinc in female mice, probably through
      changing AP-3 delta expression. Since synaptic zinc may play a key role in
      neuronal death in acute brain injury as well as in plaque formation in
      Alzheimer's disease, and since estrogen may be beneficial in both conditions, our
      results may provide new insights into the effects of estrogen on the brain.

PMID- 14681235
TI  - Induction of cytotoxic T-lymphocyte antigen-2beta, a cysteine protease inhibitor
      in decidua: a potential regulator of embryo implantation.
AB  - During early pregnancy, the steroid hormone progesterone induces differentiation
      of uterine stroma to decidual cells, which regulate embryo-uterine interactions.
      The progesterone-induced signaling molecules that participate in the formation
      and function of decidua remain poorly understood. We recently utilized high
      density oligonucleotide microarrays to identify several genes whose expression is
      markedly altered in pregnant uterus in response to RU486, a well characterized
      antagonist of the progesterone receptor (PR). Our study revealed that the gene
      encoding cytotoxic T-lymphocyte antigen-2beta (CTLA-2beta), a cysteine protease
      inhibitor, is expressed during PR-induced decidualization. The spatio-temporal
      expression of CTLA-2beta mRNA precisely overlapped with the decidual phase of
      pregnancy. Interestingly, administration of progesterone to estrogen-primed
      ovariectomized mice failed to induce CTLA-2beta expression. A concomitant
      artificial decidual stimulation was necessary to trigger this expression. Uteri
      of PR knockout mice failed to express this mRNA, even after a combined
      administration of steroid hormones and artificial stimulation. The uterine
      expression of CTLA-2beta was, therefore, dependent on PR as well as other unknown
      factor(s) associated with decidual response. To identify the molecular target(s)
      of CTLA-2beta,we analyzed its interaction with proteins present in soluble
      extracts prepared from day 7 pregnant uteri containing implanted embryos. A
      protein affinity strategy employing recombinant CTLA-2beta helped us to determine
      that cathepsin L, a cysteine protease, is one of its targets in the pregnant
      uterus. Consistent with this finding, expression of cathepsin L was detected in
      the giant trophoblast cells of the ectoplacental cone on day 7 of pregnancy.
      Collectively, our results support the hypothesis that expression of CTLA-2beta in
      the decidua may regulate implantation of the embryo by neutralizing the
      activities of one or more proteases generated by the proliferating trophoblast.

PMID- 14681236
TI  - Differential inhibition of membrane type 3 (MT3)-matrix metalloproteinase (MMP)
      and MT1-MMP by tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-3 rgulates
      pro-MMP-2 activation.
AB  - The membrane type (MT)-matrix metalloproteinases (MMPs) constitute a subgroup of
      membrane-anchored MMPs that are major mediators of pericellular proteolysis and
      physiological activators of pro-MMP-2. The MT-MMPs also exhibit differential
      inhibition by members of the tissue inhibitor of metalloproteinase (TIMP) family.
      Here we investigated the processing, catalytic activity, and TIMP inhibition of
      MT3-MMP (MMP-16). Inhibitor profile and mutant enzyme studies indicated that MT3
      MMP is regulated on the cell surface by autocatalytic processing and ectodomain
      shedding. Inhibition kinetic studies showed that TIMP-3 is a high affinity
      inhibitor of MT3-MMP when compared with MT1-MMP (K(i) = 0.008 nm for MT3-MMP
      versus K(i) = 0.16 nm for MT1-MMP). In contrast, TIMP-2 is a better inhibitor of
      MT1-MMP. MT3-MMP requires TIMP-2 to accomplish full pro-MMP-2 activation and this
      process is enhanced in marimastatpretreated cells, consistent with regulation of
      active enzyme turnover by synthetic MMP inhibitors. TIMP-3 also enhances the
      activation of pro-MMP-2 by MT3-MMP but not by MT1-MMP. TIMP-4, in contrast,
      cannot support pro-MMP-2 activation with either enzyme. Affinity chromatography
      experiments demonstrated that pro-MMP-2 can assemble trimolecular complexes with
      a catalytic domain of MT3-MMP and TIMP-2 or TIMP-3 suggesting that pro-MMP-2
      activation by MT3-MMP involves ternary complex formation on the cell surface.
      These results demonstrate that TIMP-3 is a major regulator of MT3-MMP activity
      and further underscores the unique interactions of TIMPs with MT-MMPs in the
      control of pericellular proteolysis.

PMID- 14681238
TI  - Pro-thrombotic state induced by post-translational modification of fibrinogen by
      reactive nitrogen species.
AB  - Formation of nitric oxide-derived oxidants has been linked to development of
      atherosclerosis and associated thrombotic complications. Although systemic levels
      of protein nitrotyrosine predict risk for coronary artery disease, neither
      specific proteins targeted for modification nor functional consequences that
      might contribute to disease pathogenesis have been defined. Here we report a
      selective increase in circulating levels of nitrated fibrinogen in patients with
      coronary artery disease. Exposure of fibrinogen to nitrating oxidants, including
      those produced by the myeloperoxidase-hydrogen peroxide-nitrite system,
      significantly accelerates clot formation and factor XIII cross-linking, whereas
      exposure of fibrinogen to non-nitrating oxidants decelerates clot formation.
      Clots formed with fibrinogen exposed to nitrating oxidants are composed of large
      bundles made from twisted thin fibrin fibers with increased permeation and a
      decrease in storage modulus G' value, suggesting that these clots could be easily
      deformed by mechanical stresses. In contrast, clots formed with fibrinogen
      exposed to non-nitrating oxidants showed decreased permeation with normal
      architecture. Fibrinogen modified by exposure to physiologic nitration systems
      demonstrated no difference in the rate of plasmin-induced clot lysis, platelet
      aggregation, or binding. Thus, increased levels of fibrinogen nitration may lead
      to a pro-thrombotic state via acceleration in formation of fibrin clots. The
      present results may account, in part, for the association between nitrative
      stress and risk for coronary artery disease.

PMID- 14681237
TI  - Ras induction of superoxide activates ERK-dependent angiogenic transcription
      factor HIF-1alpha and VEGF-A expression in shock wave-stimulated osteoblasts.
AB  - Vascular endothelial growth factor (VEGF) released by osteoblasts plays an
      important role in angiogenesis and endochondral ossification during bone
      formation. In animal studies, we have reported that shock waves (SW) can promote
      osteogenic differentiation of mesenchymal stem cells through superoxide-mediated
      signal transduction (Wang, F. S., Wang, C. J., Sheen-Chen, S. M., Kuo, Y. R.,
      Chen, R. F., and Yang, K. D. (2002) J. Biol. Chem. 277, 10931-10937) and
      vascularization of the bone-tendon junction. Here, we found that SW elevation of
      VEGF-A expression in human osteoblasts to be mediated by Ras-induced superoxide
      and ERK-dependent HIF-1alpha activation. SW treatment (0.16 mJ/mm(2), 1 Hz, 500
      impulses) rapidly activated Ras protein (15 min) and Rac1 protein (30 min) and
      increased superoxide production in 30 min and VEGF mRNA expression in 6 h. Early
      scavenging of superoxide, but not nitric oxide, peroxide hydrogen, or
      prostaglandin E(2), reduced SW-augmented VEGF-A levels. Inhibition of superoxide
      production by diphenyliodonium, an NADPH oxidase inhibitor, was found to suppress
      VEGF-A expression. Transfection of osteoblasts with a dominant negative (S17N)
      Ras mutant abrogated the SW enhancement of Rac1 activation, superoxide synthesis,
      and VEGF expression. Further studies demonstrated that SW significantly promoted
      ERK activation in 1 h and HIF-1alpha phosphorylation and HIF-1alpha binding to
      VEGF promoter in 3 h. In support of the observation that superoxide mediated the
      SW-induced ERK activation and HIF-1alpha transactivation, we further demonstrated
      that scavenging of superoxide by superoxide dismutase and inhibition of ERK
      activity by PD98059 decreased HIF-1alpha activation and VEGF-A levels. Moreover,
      culture medium harvested from SW-treated osteoblasts increased vessel number of
      chick chorioallantoic membrane. Superoxide dismutase pretreatment and anti-VEGF-A
      antibody neutralization reduced the promoting effect of conditioned medium on
      angiogenesis. Thus, modulation of redox reaction by SW may have some positive
      effect on angiogenesis during bone regeneration.

PMID- 14681239
TI  - Randomization, trials and tribulations.

PMID- 14681240
TI  - Suicide by intentional ingestion of pesticides: a continuing tragedy in
      developing countries.

PMID- 14681241
TI  - The Doctor's Dilemma.

PMID- 14681243
TI  - Commentary: A very Fabian dilemma.

PMID- 14681244
TI  - Commentary: Bernard Shaw's dilemma: marked by mortality.

PMID- 14681245
TI  - Commentary: Shaw's critique of health care is still valid.

PMID- 14681246
TI  - Fisher and Bradford Hill: theory and pragmatism?

PMID- 14681247
TI  - Fisher, Bradford Hill, and randomization.

PMID- 14681248
TI  - Fisher and Bradford Hill: their personal impact.

PMID- 14681249
TI  - Rigorous uncertainty: why RA Fisher is important.

PMID- 14681250
TI  - RA Fisher, statistician and geneticist extraordinary: a personal view.

PMID- 14681251
TI  - Spies, magicians, and Enid Blyton: how they can help improve clinical trials.

PMID- 14681253
TI  - Photoessay. Childhood.

PMID- 14681254
TI  - The associations of social class and social stratification with patterns of
      general and mental health in a Spanish population.
AB  - BACKGROUND: Social class, as a theoretical framework, represents a complementary
      approach to social stratification by introducing social relations of ownership
      and control over productive assets to the analysis of inequalities in economic,
      political, and cultural resources. In this study we examined whether measures of
      social class were able to explain and predict self-reported general and mental
      health over and above measures of social stratification. METHODS: We tested this
      using the Barcelona Health Interview Survey, a cross-sectional survey of 10 000
      residents of the city's non-institutionalized population in 2000. We used Erik
      Olin Wright's indicators of social class position, based on ownership and control
      over productive assets. As measures of social stratification we used the Spanish
      version of the British Registrar General (BRG) classification, and education.
      Health-related variables included self-perceived health and mental health as
      measured by Goldberg's questionnaire. RESULTS: Among men, high level managers and
      supervisors reported better health than all other classes, including small
      business owners. Low-level supervisors reported worse mental health than high
      level managers and non-managerial workers, giving support to Wright's
      contradictory class location hypothesis with regard to mental health. Social
      class indicators were less useful correlates of health and mental health among
      women. CONCLUSIONS: Our findings highlight the potential health consequences of
      social class positions defined by power relations within the labour process. They
      also confirm that social class taps into parts of the social variation in health
      that are not captured by conventional measures of social stratification and
      education.

PMID- 14681255
TI  - Commentary: Relating social structure and health.

PMID- 14681256
TI  - Antidepressant medication use and breast cancer risk: a case-control study.
AB  - BACKGROUND: Animal and human studies have reported an association between
      antidepressant (AD) medication use and breast cancer risk. A population-based
      case-control study was designed specifically to examine this association among
      women in Ontario, Canada. METHODS: The Ontario Cancer Registry (OCR) identified
      women diagnosed with primary breast cancer. Controls, randomly sampled from the
      female population of Ontario, were frequency matched by 5-year age groups. A
      mailed self-administered questionnaire included questions about lifetime use of
      AD and potential confounders. Multivariate logistic regression yielded odds ratio
      estimates. RESULTS: 'Ever' use of AD was reported by 14% (441/3077) cases versus
      12% (372/2994) controls. The age-adjusted odds ratio (AOR) for 'ever' use was
      1.17, (95% CI: 1.01, 1.36). An increased risk was also observed for selective
      serotonin reuptake inhibitors = 1.33 (95% CI: 1.07, 1.66), Sertraline = 1.58 (95%
      CI: 1.03, 2.41), and Paroxetine = 1.55 (95% CI: 1.00, 2.40). None of the 30
      variables assessed for confounding altered the risk estimate by more than 10%.
      Multivariate adjustment including all possible breast cancer risk factors yielded
      an unchanged, but not significant, point estimate (MVOR = 1.2, 95% CI: 0.96,
      1.51). No relationship was observed for duration or timing of AD use.
      CONCLUSIONS: A modest association between 'ever' use of AD and breast cancer was
      found using the most parsimonious multivariate model. OR estimates did not
      change, but CI were widened and statistical significance lost, after adjustment
      for factors associated with breast cancer risk.

PMID- 14681257
TI  - Commentary: Antidepressants and breast cancer risk.

PMID- 14681258
TI  - Contribution of adolescent and early adult personality to the inverse association
      between education and cardiovascular risk behaviours: prospective population
      based cohort study.
AB  - BACKGROUND: The role of early personality in socioeconomic inequalities in health
      is not well understood. We investigated the extent to which type A components in
      adolescence and early adulthood contributed to the inverse association between
      education and behavioural cardiovascular disease risk factors in adulthood.
      METHODS: Prospective cohort study with a population-based random sample of 477
      men and 648 women, aged 12-21 years at baseline. Baseline data included
      information on pathogenic and protective components of type A behaviours
      (impatience, aggression, hard-driving, and engagement-involvement) and parental
      education. The 9-year follow-up data included information on the participant's
      educational level and health behaviours (smoking, alcohol consumption, physical
      inactivity, butter use). RESULTS: After adjustment for parental education, high
      levels of impatience and low levels of hard-driving in adolescence and early
      adulthood predicted low educational level in adulthood (Ps < 0.01 for men, Ps <
      0.001 for women). Adulthood education was inversely associated with smoking in
      women and men (odds ratios [OR] = 8.5 and 7.9, 95% CI: 3.4-18.4 and 3.1-23.9,
      respectively), and with physical inactivity in women (OR = 5.4, 95% CI: 2.6
      11.4). In men, components of type A behaviour explained 28.5% of the inverse
      association between education and smoking, even after controlling for parental
      education. In women, the corresponding proportions were 20.5% and 17.7% for
      smoking and physical inactivity, respectively. CONCLUSIONS: The inverse
      associations of adulthood education with smoking in men and women and physical
      inactivity in women may be partly rooted in personality-related factors present
      earlier in life. Our evidence suggests that personality should be studied as a
      potential contributor to socioeconomic differences in health behaviours.

PMID- 14681259
TI  - Commentary: Personality and the socioeconomic-health gradient.

PMID- 14681260
TI  - Morbidity profile and its relationship with disability and psychological distress
      among elderly people in Northern India.
AB  - BACKGROUND: Morbidity among elderly people has an important influence on their
      physical functioning and psychological well-being. Evaluation of the morbidity
      profile and its determinants, which have implications for elderly people, are not
      available. The objective of this study is to assess morbidity, co-morbidity, and
      patterns of treatment seeking, and to determine relationship of morbidity with
      disability, psychological distress, and socio-demographic variables among the
      elderly population in northern India. METHODS: A cross-sectional survey of 200
      subjects over 60 years old (100 each from the urban population of Chandigarh City
      and the rural population of Haryana State of India) was carried out using a
      cluster sampling technique. The study period was July 1999-April 2000. Various
      socio-demographic characteristics were recorded at baseline. A clinical diagnosis
      was made by a physician based on reported illness, clinical examination, and
      cross-checking of medical records and medications held by the subjects.
      Psychological distress and disability was assessed using the PGI-Health
      Questionnaire-N-1 and the Rapid Disability Rating Scale-2, respectively. ANOVA,
      Kruskal-Wallis H test, correlation coefficient, and multivariate analysis were
      used to assess the relationship and association of morbidity with other
      variables. RESULTS: Of the total sample, 88.9% reported illness based on their
      perception, and of these 43.5% were seeking treatment and actually taking
      medicines, and 42.5% were diagnosed as having 4-6 morbidities. The mean number of
      morbidities among elderly people was 6.1 (SD 2.9). A total of 87.5% had minimal
      to severe disabilities and 66% of elderly people were distressed physically,
      psychologically, or both. The most prevalent morbidity was anaemia, followed by
      dental problems, hypertension, chronic obstructive airway disease (COAD),
      cataract, and osteoarthritis. Morbidities like asthma, COAD, hypertension,
      osteoarthritis, gastrointestinal disorders, anaemia, and eye and neurological
      problems were significantly associated with disability and distress. Higher
      number of morbidities was associated with greater disability and distress. In
      univariate analysis, socio-demographic variables like age, locality, caste,
      education, occupation, and income were important determinants of morbidity.
      Multivariate analysis was undertaken to find out the independent relationship of
      socio-demographic variables with morbidity. Morbidity was significantly
      associated with age (b value 0.06, 95% CI: 0.01, 0.12), sex (b value 1.03, 95%
      CI: 0.02, 2.05), and occupation (b value 0.20, 95% CI: 0.07, 0.33). CONCLUSIONS:
      A high mean number of morbidities (6.1, SD 2.9) was observed. Elderly subjects
      with higher morbidity had increasing disability and distress. Age, sex, and
      occupation were important determinants of morbidity. Assessment of the morbidity
      profile and its determinants will help in the application of interventions, both
      medical and social, to improve the health status and thus the quality of life of
      the elderly in Northern India.

PMID- 14681261
TI  - Commentary: Disability amongst elderly people world-wide: the need for multi
      dimensional health assessment.

PMID- 14681262
TI  - Vital exhaustion as a risk factor for ischaemic heart disease and all-cause
      mortality in a community sample. A prospective study of 4084 men and 5479 women
      in the Copenhagen City Heart Study.
AB  - BACKGROUND: Vital exhaustion, a psychological measure characterized by fatigue
      and depressive symptoms, has been suggested to be an independent risk factor for
      ischaemic heart disease (IHD) but the generality of the phenomenon remains in
      question. The aim of this study is to describe prevalence of these symptoms in a
      community sample and determine whether they prospectively predict increased risk
      of IHD and all-cause mortality in men and women. METHODS: The study base was 4084
      men and 5479 women aged 20-98 free of IHD examined in 1991-1993 in the Copenhagen
      City Heart Study. Events were ascertained through record linkage until 1998 for
      IHD and September 2000 for all-cause mortality. There were 483 first hospital
      admissions and deaths caused by IHD and 1559 deaths from all causes during follow
      up. RESULTS: The 17 items on the vital exhaustion questionnaire were frequently
      endorsed with prevalence ranging from 6 to 47 per cent, higher in women. All but
      4 of the 17 items were significantly associated with IHD with significant
      relative risks (RR) ranging between 1.36 (95% CI: 1.08, 1.72) and 2.10 (95% CI:
      1.63, 2.71). Associations with all-cause mortality were also observed, but were
      weaker. RR of both IHD and all-cause mortality increased with increasing item sum
      score and were similar in men and women. For IHD, RR reached a maximum of 2.57
      (95% CI: 1.65, 4.00) for subjects endorsing >9 items. The similar RR for all
      cause mortality was 2.50 (95% CI: 2.09, 2.99). Multivariate adjustment for
      biological, behavioural, and socioeconomic risk factors did not substantially
      affect the association for IHD but attenuated the association with all-cause
      mortality. CONCLUSIONS: Measures of fatigue and depression were common symptoms
      in this population sample and convey increased risk of IHD and of all-cause
      mortality. We propose this knowledge begin to be implemented in risk assessment
      in clinical practice.

PMID- 14681263
TI  - Commentary: What should we make of associations between vital exhaustion and
      heart disease?

PMID- 14681264
TI  - Smoking at age 18-20 and suicide during 26 years of follow-up-how can the
      association be explained?
AB  - OBJECTIVES: Several studies have shown a relation between smoking and suicide. It
      is not clear if this relation should be considered causal, or if other risk
      factors for suicide, left unmeasured in many studies, might explain the smoking
      suicide association. The aim of this cohort study was to analyse the role of
      smoking and other potential risk factors measured in adolescence on subsequent
      suicide. METHODS: Information on smoking, and other potential risk factors from
      childhood and adolescence was collected among 49 323 men, born 1949-1951, at
      conscription for compulsory military training in the years 1969-1970. Mortality
      data were obtained from the Swedish cause of death register for the years 1971
      1996. RESULTS: There was a clear trend of increasing suicide risk with increasing
      intensity of smoking reported at conscription. Those smoking >20 cigarettes/day
      had a strongly increased relative risk of suicide (OR = 3.03, 95% CI: 1.72, 5.34)
      during the first 13 years of follow-up. From 14 to 26 years after conscription,
      the risk was only slightly weaker (OR = 2.53, 95% CI: 1.36, 4.72). When we
      adjusted for other risk factors for suicide measured at the conscription
      examination (psychiatric diagnosis, parental divorce, low emotional control,
      medication for nervous problems, contact with police and childcare, heavy alcohol
      consumption, drug use, and education) in a multivariate analysis, the trend with
      smoking intensity disappeared, and there was no longer an increased relative risk
      for the heavy smokers (follow-up years 1-13: OR = 0.98, 95% CI: 0.53, 1.82; years
      14-26: OR = 1.31, 95% CI: 0.91, 1.87). CONCLUSION: The increased risk of suicide
      among smokers was almost entirely explained by an increased prevalence of heavy
      alcohol consumption and low mental well-being among smokers. That is, the
      association between smoking and suicide is probably due to confounding by these
      other factors. These results do not support the hypothesis that tobacco
      consumption itself is a risk factor for suicide.

PMID- 14681265
TI  - Commentary: Questionable premises, overadjustment, and a smoking/suicide
      association in younger adult men.

PMID- 14681266
TI  - Suicides after the 1999 Taiwan earthquake.
AB  - BACKGROUND: The impact of a disaster on extreme post-traumatic responses of the
      victims, such as suicide, remains unclear. We conducted this study to investigate
      the risk of committing suicide between victims and non-victims after the 1999
      Taiwan earthquake. METHODS: This population cohort study linked the National
      Health Insurance files, family registration, and death certificates. It consists
      of the 3 432 705 residents aged >/=15 years of central Taiwan, 1998-2000. They
      were stratified into victims (n = 301 327) and non-victims (n = 3 131 378).
      Victims refer to those who lost co-resident family members, were injured, or
      experienced property loss during the earthquake. Non-victims refers to all
      others. The suicide rate was calculated for the period 2-15 months after the
      earthquake. Adjusted odds ratios were estimated with logistic regression.
      RESULTS: After adjusting for residential location, age, gender, major disease
      status, and level of urbanization, we found that victims were 1.46 times more
      likely than non-victims to commit suicide following an earthquake (95% CI: 1.11,
      1.92). CONCLUSIONS: Given the large study population and individual information
      available to identify victim status, this study was able to detect a
      statistically significant earthquake effect on suicide rate. This effect on
      suicide might be diluted if only geographically based stratification were
      possible, as opposed to victim status stratifications. Mental health programmes
      or other preventive strategies might be more effective by specifically targeting
      victims rather than by simply targeting individuals living in earthquake-affected
      areas.

PMID- 14681267
TI  - Health inequalities in the workforce: the labour market core-periphery structure.
AB  - OBJECTIVES: To explore health inequalities between six labour market groups
      ranging from permanent employees to the long-term unemployed receiving minimum
      daily allowance. METHODS: A sample of 15 468 employees or job seekers from a
      population survey. Their perceived health, diseases, and depression were
      measured. RESULTS: Compared with permanent employees, the odds for poor health
      were highest among the unemployed with low incomes irrespective of adjustments,
      across all health indicators and in both men and women. High odds were also found
      among the less disadvantaged unemployed and the employed with atypical contracts,
      but not among fixed-term employees. CONCLUSIONS: Rather than between the employed
      and the unemployed, it seems that health inequalities prevail across different
      labour market groups within the employed and the unemployed. Future studies
      should employ a more detailed classification of employment situation.

PMID- 14681268
TI  - The association between state income inequality and worse health is not
      confounded by race.
AB  - BACKGROUND: The relationship between income inequality and health across US
      states has been challenged recently on grounds that this relationship may be
      confounded by the effect of racial composition, measured as the proportion of the
      state's population who are black. METHODS: Using multilevel statistical models,
      we examined the association between state income inequality and poor self-rated
      health. The analysis was based on the pooled 1995 and 1997 Current Population
      Surveys, comprising 201 221 adults nested within 50 US states. RESULTS:
      Controlling for the individual effects of age, sex, race, marital status,
      education, income, health insurance coverage, and employment status, we found a
      significant effect of state income inequality on poor self-rated health. For
      every 0.05-increase in the Gini coefficient, the odds ratio (OR) of reporting
      poor health increased by 1.39 (95% CI: 1.26, 1.51). Additionally controlling for
      the proportion of the state population who are black did not explain away the
      effect of income inequality (OR = 1.30; 95% CI: 1.15, 1.45). While being black at
      the individual level was associated with poorer self-rated health, no significant
      relationship was found between poor self-rated health and the proportion of black
      residents in a state. CONCLUSION: Our finding demonstrates that neither race, at
      the individual level, nor racial composition, as measured at the state level,
      explain away the previously reported association between income inequality and
      poorer health status in the US.

PMID- 14681269
TI  - Commentary: Plugging leaks and repelling boarders--where to next for the SS
      income inequality?

PMID- 14681271
TI  - Predicting the distribution of under-five deaths by cause in countries without
      adequate vital registration systems.
AB  - BACKGROUND: The absence of complete vital registration and atypical nature of the
      locations where epidemiological studies of cause of death in children are
      conducted make it difficult to know the true distribution of child deaths by
      cause in developing countries. A credible method is needed for generating valid
      estimates of this distribution for countries without adequate vital registration
      systems. METHODS: A systematic review was undertaken of all studies published
      since 1980 reporting under-5 mortality by cause. Causes of death were
      standardized across studies, and information was collected on the characteristics
      of each study and its population. A meta-regression model was used to relate
      these characteristics to the various proportional mortality outcomes, and predict
      the distribution in national populations of known characteristics. In all, 46
      studies met the inclusion criteria. RESULTS: Proportional mortality outcomes were
      significantly associated with region, mortality level, and exposure to malaria;
      coverage of measles vaccination, safe delivery care, and safe water; study year,
      age of children under surveillance, and method used to establish definitive cause
      of death. In sub-Saharan Africa and in South Asia, the predicted distribution of
      deaths by cause was: pneumonia (23% and 23%), malaria (24% and <1%), diarrhoea
      (22% and 23%), 'neonatal and other' (29% and 52%), measles (2% and 1%).
      CONCLUSIONS: For countries without adequate vital registration, it is possible to
      estimate the proportional distribution of child deaths by cause by exploiting
      systematic associations between this distribution and the characteristics of the
      populations in which it has been studied, controlling for design features of the
      studies themselves.

PMID- 14681272
TI  - Commentary: Estimating the causes of child deaths.

PMID- 14681273
TI  - A comparison of a food frequency questionnaire with a 24-hour recall for use in
      an epidemiological cohort study: results from the biomarker-based Observing
      Protein and Energy Nutrition (OPEN) study.
AB  - BACKGROUND: Most large cohort studies have used a food frequency questionnaire
      (FFQ) for assessing dietary intake. Several biomarker studies, however, have cast
      doubt on whether the FFQ has sufficient precision to allow detection of moderate
      but important diet-disease associations. We use data from the Observing Protein
      and Energy Nutrition (OPEN) study to compare the performance of a FFQ with that
      of a 24-hour recall (24HR). METHODS: The OPEN study included 484 healthy
      volunteer participants (261 men, 223 women) from Montgomery County, Maryland,
      aged 40-69. Each participant was asked to complete a FFQ and 24HR on two
      occasions 3 months apart, and a doubly labelled water (DLW) assessment and two 24
      hour urine collections during the 2 weeks after the first FFQ and 24HR
      assessment. For both the FFQ and 24HR and for both men and women, we calculated
      attenuation factors for absolute energy, absolute protein, and protein density.
      RESULTS: For absolute energy and protein, a single FFQ's attenuation factor is
      0.04-0.16. Repeat administrations lead to little improvement (0.08-0.19).
      Attenuation factors for a single 24HR are 0.10-0.20, but four repeats would yield
      attenuations of 0.20-0.37. For protein density a single FFQ has an attenuation of
      0.3-0.4; for a single 24HR the attenuation factor is 0.15-0.25 but would increase
      to 0.35-0.50 with four repeats. CONCLUSIONS: Because of severe attenuation, the
      FFQ cannot be recommended as an instrument for evaluating relations between
      absolute intake of energy or protein and disease. Although this attenuation is
      lessened in analyses of energy-adjusted protein, it remains substantial for both
      FFQ and multiple 24HR. The utility of either of these instruments for detecting
      important but moderate relative risks (between 1.5 and 2.0), even for energy
      adjusted dietary factors, is questionable.

PMID- 14681274
TI  - Commentary: An OPEN assessment of dietary measurement errors.

PMID- 14681275
TI  - Comparison of time series and case-crossover analyses of air pollution and
      hospital admission data.
AB  - BACKGROUND: Time series analysis is the most commonly used technique for
      assessing the association between counts of health events over time and exposure
      to ambient air pollution. Recently, case-crossover analysis has been proposed as
      an alternative analytical approach. While each technique has its own advantages
      and disadvantages, there remains considerable uncertainty as to which statistical
      methodology is preferable for evaluating data of this type. METHODS: The
      objective of this paper is to evaluate the performance of different variations of
      these two procedures using computer simulation. Hospital admission data were
      generated under realistic models with known parameters permitting estimates based
      on time series and case-crossover analyses to be compared with these known
      values. RESULTS: While accurate estimates can be achieved with both methods, both
      methods require some decisions to be made by the researcher during the course of
      the analysis. With time series analysis, it is necessary to choose the time span
      in the LOESS smoothing process, or degrees of freedom when using natural cubic
      splines. For case-crossover studies using either uni- or bi-directional control
      selection strategies, the choice of time intervals needs to be made. CONCLUSIONS:
      We prefer the times series approach because the best estimates of risk that can
      be obtained with time series analysis are more precise than the best estimates
      based on case-crossover analysis.

PMID- 14681276
TI  - Commentary: Comparison of time series and case-crossover analyses of air
      pollution and hospital admission data.

PMID- 14681277
TI  - Efficiency of two-phase designs for prevalence estimation.
AB  - BACKGROUND: Unbiased estimation of the prevalence of diseases and other
      conditions is important but can be expensive, especially for conditions which do
      not necessarily lead to contact with health services. A two-phase population
      survey may seem an attractive option when there is a relatively cheap, although
      fallible, test for disease status available: the test is used in the first phase
      of the survey but in the second, only a subsample are classified by the
      relatively expensive, gold standard. Previously the cost efficiency of such
      studies compared with simple, one-phase random sample designs was investigated
      empirically and some questions remain unclear. METHODS: A simple formula for the
      maximum reduction in cost or standard error that can be achieved by two-phase
      sampling compared with simple random sampling is derived mathematically. A
      formula for the minimum reduction is also given and the influence of prevalence
      on efficiency explained. RESULTS: The main result shows that the sensitivity and
      specificity of the first stage test set an absolute limit on the efficiency of
      two-phase designs; in particular, two-phase sampling can never be justified on
      efficiency grounds alone if the test is not accurate enough.

PMID- 14681278
TI  - Commentary: Two-phase surveys. A death is announced; no flowers please.

PMID- 14681279
TI  - Estonia 1989-2000: enormous increase in mortality differences by education.
AB  - BACKGROUND: Having regained its political autonomy in 1991, Estonia experienced
      major changes in political, economic, and social realities. We aimed to analyse
      mortality changes by education from 1989 to 2000 in order to assess the impact of
      recent changes in Estonia, as well as the delayed effects of pre-transitional
      developments. METHODS: Two census-based analyses were compared. Individual cause
      specific death data for those aged 20+ for 1987-1990 (72 003 deaths) and 1999
      2000 (35 477 deaths) came from the national mortality database. Population
      denominators came from the population censuses of 1989 and 2000. Mortality for
      all causes combined and for selected causes of death were analysed for high, mid,
      and low educational groups. The absolute differences in mortality were evaluated
      through life expectancy at age 25 and age-standardized mortality rates. To assess
      the relative differences between educational levels, mortality rate ratios with
      95% CI were calculated using Poisson regression. RESULTS: Educational differences
      in mortality increased tremendously from 1989 to 2000: over the 10-year period
      life expectancy improved considerably for graduates, and worsened for those with
      the lowest education. In 2000, male graduates aged 25 could expect to live 13.1
      years longer than corresponding men with the lowest education; among women the
      difference was 8.6 years. Large differences were observed in all selected causes
      of death in 1989 and in 2000 and the trends were invariably much more favourable
      for the higher educated. Educational differences in total mortality increased in
      all age groups. CONCLUSIONS: Social disruption and increasing inequalities in
      wealth can be considered main recent determinants; however, causal processes,
      shaped decades before recent reforms, also contribute to this widening gap.

PMID- 14681280
TI  - Commentary: Winners and losers.

PMID- 14681281
TI  - Education, income, and functional limitation transitions among American adults:
      contrasting onset and progression.
AB  - BACKGROUND: Although a robust association between socioeconomic status and health
      has been shown in past research, the processes that explain the connection are
      not well understood. This paper seeks to advance such understanding in two ways,
      first by attending to the distinction between onset of a functional health
      problem and its progression, and second by addressing whether and how education
      and income relate differently to the onset versus progression of functional
      health problems. METHODS: Data come from the Americans' Changing Lives survey (n
      = 3617). The baseline was conducted in 1986 and outcome status measured in 1994.
      Activity limitations are categorized into none, mild, moderate, severe. Onset is
      defined as having no limitation at origin and a limitation at outcome.
      Progression is defined as limitation of a particular severity at origin and
      improving, staying the same, or getting worse with respect to the severity.
      Multinomial regressions determine transition probabilities related to onset and
      progression. RESULTS: Those with higher income and education are less likely to
      experience an onset. Only income associates with progression. Those with the
      highest income are most likely to improve and least likely to get worse in
      comparison to those with the lowest income. CONCLUSIONS: Education, being
      determined early in life and influencing psychosocial mechanisms throughout life,
      may have a greater impact on prevention of activity and functional disorders.
      Income's role may be both as a prevention factor and as a mechanism for
      management of health problems.

PMID- 14681282
TI  - Effect of zinc supplementation on growth in West African children: a randomized
      double-blind placebo-controlled trial in rural Burkina Faso.
AB  - OBJECTIVE: To analyse the effects of zinc supplementation on growth parameters in
      a representative sample of young children in rural Burkina Faso. Design
      Randomized, double-blind, placebo-controlled efficacy trial. Setting Eighteen
      villages in rural northwestern Burkina Faso. Subjects In all, 709 children aged 6
      31 months were enrolled; 685 completed the trial. Intervention Supplementation
      with zinc (12.5 mg zinc sulphate) or placebo daily for 6 days a week for 6
      months. Outcomes Weight, length/height, mid-arm circumference, and serum zinc.
      RESULTS: In a representative subsample of study children, 72% were zinc-deficient
      at baseline. After supplementation, serum zinc increased in zinc-supplemented but
      not in control children of the subsample. No significant differences between
      groups were observed during follow-up regarding length/height, weight, mid-arm
      circumference, and z scores for height-for-age, weight-for-age, and weight-for
      height. CONCLUSIONS: We conclude that zinc supplementation does not have an
      effect of public health importance on growth in West African populations of young
      children with a high prevalence of malnutrition. Multinutrient interventions are
      likely to be more effective.

PMID- 14681283
TI  - Commentary: Zinc and child growth.

PMID- 14681284
TI  - Negative relationships between growth in height and levels of cholesterol in
      puberty: a 3-year follow-up study.
AB  - BACKGROUND: Previously, there were only a few reports on the negative
      relationship between pubertal growth in height and levels of serum lipid in boys.
      Detailed information on both genders is needed. METHODS: We investigated the
      relationship between pubertal growth in height and serum lipid. Subjects were
      1442 boys and 1350 girls followed up from age 10-11 years (the fifth grade level
      of elementary school) to age 13-14 years (the second year of junior high school).
      Anthropometric variables and serum lipids were measured by the same protocol at
      both ages. RESULTS: From cross-sectional analysis, at both ages negative
      relationships between total cholesterol levels and height were found in both
      genders. On longitudinal analysis, height at age 10-11 years was one of the
      factors predicting the level of total cholesterol at age 13-14 years. In
      addition, negative relationships between increase in height and change in serum
      lipids (total cholesterol and high density lipoprotein cholesterol) over the 3
      year period were obtained in both genders. Thus, pubertal children who experience
      a large increase in height tended to show a decrease in serum lipids, and
      children who experience a small increase in height tended to show an increase in
      serum lipids. CONCLUSION: In both genders, total cholesterol level in pubertal
      children is negatively associated with height. Height velocity is inversely
      associated with dynamic changes in serum lipids during puberty.

PMID- 14681285
TI  - Commentary: The association between height growth and cholesterol levels during
      puberty: implications for adult health.

PMID- 14681286
TI  - Case-control studies of screening should carry a health warning. Response.

PMID- 14681287
TI  - Epidemiology through the eyes of clinicians.

PMID- 14681288
TI  - Access to data from European registries for epidemiological research: results
      from a survey by the International Epidemiological Association European
      Federation.

PMID- 14681289
TI  - Is there a Mediterranean migrants mortality paradox in Europe?

PMID- 14681290
TI  - Food insecurity definitions and body mass index. Response.

PMID- 14681291
TI  - Detecting population stratification using a panel of single nucleotide
      polymorphisms.

PMID- 14681296
TI  - Developmentally regulated functions of the H19 differentially methylated domain.
AB  - Igf2 and H19 are physically linked imprinted genes. In embryonic liver, their
      reciprocal expression (paternal for Igf2 and maternal for H19) is controlled by a
      paternally methylated region (H19 DMD) located 5' of H19. This region contains a
      methylation-sensitive insulator that prevents the Igf2 promoters being activated
      by downstream enhancers on the maternal chromosome. In adult liver, Igf2 is
      normally not expressed but is reactivated upon tumour formation. By analysing
      three deletions of the H19 locus, we investigated the mechanism regulating the
      imprinted expression of the Igf2 gene in the course of liver tumourigenesis. We
      observed that the role of the H19 DMD in the control of Igf2 expression changes
      during tumourigenesis. The H19 DMD is required on the paternal chromosome for
      Igf2 activation in the early stages while its maternal allele is necessary for
      maintaining Igf2 imprinting only in the late stages. A positive regulatory
      function of the paternal H19 DMD is also evident in normal neonatal liver, but
      its relevance for Igf2 expression becomes higher in the second post-natal week.
      Our results support a model in which both methylated and non-methylated parental
      copies of the H19 DMD have active roles in the regulation of Igf2 expression in
      the liver and these activities are under developmental control.

PMID- 14681297
TI  - Limited capacity of the nuclear matrix to bind telomere repeat binding factor
      TRF1 may restrict the proliferation of mortal human fibroblasts.
AB  - The maintenance of telomere integrity is essential for prolonged cell
      proliferation, and failure in this mechanism is a most consistent manifestation
      of cellular senescence. In this study, we investigated the role of telomere
      repeat binding factor (TRF1) in the proliferation of human fibroblasts. TRF1
      expression is upregulated in a large variety of immortal human cells and supports
      de novo telomere formation in a dose-dependent manner. These observations suggest
      that the suppression of TRF1 might limit telomere maintenance and thus the life
      span of mortal cells. However, primary fibroblasts ectopically overexpressing
      TRF1 were unable to avoid senescence. On the other hand, exogenously expressed
      TRF1 in primary fibroblasts neither supported de novo telomere formation nor
      bound to the nuclear matrix as tightly as observed in immortal cells that show
      upregulated TRF1 expression. We present evidence suggesting that mortal human
      cells lack specific ligand(s) that anchor TRF1 to the nuclear matrix and that
      this contributes to their limited lifespan.

PMID- 14681298
TI  - Temporal gene expression profiling of dystrophin-deficient (mdx) mouse diaphragm
      identifies conserved and muscle group-specific mechanisms in the pathogenesis of
      muscular dystrophy.
AB  - Mutations in dystrophin are the proximate cause of Duchenne muscular dystrophy
      (DMD), but pathogenic mechanisms linking the absence of dystrophin from the
      sarcolemma to myofiber necrosis are not fully known. The muscular dystrophies
      also have properties not accounted for by current disease models, including the
      temporal delay to disease onset, broad species differences in severity, and
      diversity of skeletal muscle responses. To address the mechanisms underlying the
      differential targeting of muscular dystrophy, we characterized temporal
      expression profiles of the diaphragm in dystrophin-deficient (mdx) mice between
      postnatal days 7 and 112 using oligonucleotide microarrays and contrasted these
      data with published hindlimb muscle data. Although the diaphragm and hindlimb
      muscle groups differ in severity of response to dystrophin deficiency, and
      exhibited substantial divergence in some transcript categories including
      inflammation and muscle-specific genes, our data show that the general mechanisms
      operative in muscular dystrophy are highly conserved. The two muscle groups
      principally differed in expression levels of differentially regulated genes, as
      opposed to the non-conserved induced/repressed transcripts defining fundamentally
      distinct mechanisms. We also identified a postnatal divergence of the two wild
      type muscle group expression profiles that temporally correlated with the onset
      and progression of the dystrophic process. These findings support the hypothesis
      that conserved disease mechanisms interacting with baseline differences in muscle
      group-specific transcriptomes underlie their differential responses to DMD. We
      further suggest that muscle group-specific transcriptional profiles contribute
      toward the muscle targeting and sparing patterns observed for a variety of
      metabolic and neuromuscular diseases.

PMID- 14681299
TI  - Defective bone mineralization and osteopenia in young adult FGFR3-/- mice.
AB  - Mutations that cause constitutive activation of fibroblast growth factor receptor
      3 (FGFR3) result in skeletal disorders that are characterized by short-limbed
      dwarfism and premature closure of cranial sutures. In previous work, it was shown
      that congenital deficiency of FGFR3 led to skeletal overgrowth. Using a
      combination of imaging, classic histology and molecular cell biology we now show
      that young adult FGFR3(-/-) mice are osteopenic due to reduced cortical bone
      thickness and defective trabecular bone mineralization. The reduction in
      mineralized bone and lack of trabecular connectivity observed by micro-computed
      tomography were confirmed in histological and histomorphometric analyses, which
      revealed a significant decrease in calcein labelling of mineralizing surfaces and
      a significant increase in osteoid in the long bones of 4-month-old FGFR3(-/-)
      mice. These alterations were associated with increased staining for recognized
      markers of differentiated osteoblasts and increased numbers of tartrate-resistant
      acid phsophatase postitive osteoclasts. Primary cultures of adherent bone marrow
      derived cells from FGFR3(-/-) mice expressed markers of differentiated
      osteoblasts but developed fewer mineralized nodules than FGFR3(+/+) cultures of
      the same age. Our observations reveal a role for FGFR3 in post-natal bone growth
      and remodelling, which identifies it as a potential therapeutic target for
      osteopenic disorders and those associated with defective bone mineralization.

PMID- 14681300
TI  - Defining haplotype blocks and tag single-nucleotide polymorphisms in the human
      genome.
AB  - Recent studies suggest that the genome is organized into blocks of haplotypes,
      and efforts to create a genome-wide haplotype map of single-nucleotide
      polymorphisms (SNPs) are already underway. Haplotype blocks are defined
      algorithmically and to date several algorithms have been proposed. However,
      little is known about their relative performance in real data or about the impact
      of allele frequencies and parameter choices on the detection of haplotype blocks
      and the markers that tag them. Here we present a formal comparison of two major
      algorithms, a linkage disequilibrium (LD)-based method and a dynamic programming
      algorithm (DPA), in three chromosomal regions differing in gene content and
      recombination rate. The two methods produced strikingly different results. DPA
      identified fewer and larger haplotype blocks as well as a smaller set of tag SNPs
      than the LD method. For both methods, the results were strongly dependent on the
      allele frequency. Decreasing the minor allele frequency led to an up to 3.7-fold
      increase in the number of haplotype blocks and tag SNPs. Definition of haploytpe
      blocks and tag SNPs was also sensitive to parameter changes, but the results
      could not be reconciled simply by parameter adjustment. These results show that
      two major methods for detecting haplotype blocks and tag SNPs can produce
      different results in the same data and that these results are sensitive to marker
      allele frequencies and parameter choices. More information is needed to guide the
      choice of method, marker allele frequencies, and parameters in the development of
      a haplotype map.

PMID- 14681301
TI  - Association of tumor necrosis factor polymorphisms with asthma and serum total
      IgE.
AB  - Tumor necrosis factors (TNF; TNFA and TNFB) are major pro-inflammatory cytokines
      that are thought to be important in the pathogenesis of asthma. However, the
      functions of genetic polymorphisms in these cytokines have not been thoroughly
      examined in the context of asthma pathology. In an effort to discover
      polymorphism(s) in genes whose variant(s) have been implicated in asthma
      phenotypes, we examined the genetic effects of TNF (TNFA and TNFB) polymorphisms
      on asthma and total serum IgE level. Seven common single-nucleotide polymorphisms
      (SNP) in TNF genes were genotyped in a Korean asthma cohort (asthmatics n=550,
      normal controls n=171). Six common haplotypes could be constructed in the TNF
      gene cluster due to very strong LD between TNFA and TNFB, located 13 kb apart on
      chromosome 6p21. One SNP (TNFA-308G>A) showed a significant association with the
      risk of asthma (P=0.0004). The frequency of TNFA-308A allele-containing genotype
      in asthmatics (9.8%) was much lower than that in normal controls (22.9%). The
      protective effects of this polymorphism on asthma were also evident in separated
      subgroups by atopic status (P=0.05 in non-atopic subjects and P=0.003 in atopic
      subjects). The most common haplotype of the TNF gene (TNF-ht1[GGTCCGG]) was
      associated with total serum IgE (immunoglobulin E) levels in asthma patients,
      especially in non-atopic patients (P=0.004). Genetic variants of TNF might be
      involved in development of asthma and total serum IgE level in bronchial asthma
      patients. The results of this study could be helpful to understand the function
      of important TNF genes in asthma and IgE production.

PMID- 14681302
TI  - Stimulation of calcineurin signaling attenuates the dystrophic pathology in mdx
      mice.
AB  - Utrophin has been studied extensively in recent years in an effort to find a cure
      for Duchenne muscular dystrophy. In this context, we previously showed that mice
      expressing enhanced muscle calcineurin activity (CnA*) displayed elevated levels
      of utrophin around their sarcolemma. In the present study, we therefore crossed
      CnA* mice with mdx mice to determine the suitability of elevating calcineurin
      activity in preventing the dystrophic pathology. Muscles from mdx/CnA* displayed
      increased nuclear localization of NFATc1 and a fiber type shift towards a slower
      phenotype. Measurements of utrophin levels in mdx/CnA* muscles revealed an
      approximately 2-fold induction in utrophin expression. Consistent with this
      induction, we also observed that members of the dystrophin-associated protein
      (DAP) complex were present at the sarcolemma of mdx/CnA* mouse muscle. This
      restoration of the utrophin-DAP complex was accompanied by significant reductions
      in the extent of central nucleation and fiber size variability. Importantly,
      assessment of myofiber sarcolemmal damage, as monitored by the intracellular
      presence of IgM and albumin as well as by Evans blue uptake in vivo, revealed a
      net amelioration of membrane integrity. Finally, immunofluorescence experiments
      using Mac-1 antibodies showed a reduction in the number of infiltrating immune
      cells in muscles from mdx/CnA* mice. These results show that elevated calcineurin
      activity attenuates the dystrophic pathology and thus provides an effective
      target for pharmacological intervention.

PMID- 14681303
TI  - Genomic imprinting at the WT1 gene involves a novel coding transcript (AWT1) that
      shows deregulation in Wilms' tumours.
AB  - The Wilms' tumour suppressor gene, WT1, is mutated in 10-15% of Wilms' tumours
      and encodes zinc-finger proteins with diverse cellular functions critical for
      nephrogenesis, genitourinary development, haematopoiesis and sex determination.
      Here we report that a novel alternative WT1 transcript, AWT1, is co-expressed
      with WT1 in renal and haematopoietic cells. AWT1 maintains WT1 exonic structure
      between exons 2 and 10, but deploys a new 5'-exon located in intron 1 of WT1. The
      AWT1 gene predicts proteins of approximately 33 kDa, comprising all exon 5 and
      exon 9 splicing variants previously characterized for WT1. Although WT1 is not
      genomically imprinted in kidney, we have previously shown monoallelic expression
      of a WT1 antisense transcript (WT1-AS) that is consistent with genomic
      imprinting. Here we demonstrate that both WT1-AS and the novel AWT1 transcript
      are imprinted in normal kidney with expression confined to the paternal allele.
      Wilms' tumours display biallelic AWT1 expression, indicating relaxation of
      imprinting of AWT1 in a subset of WTs. Our findings define human chromosome 11p13
      as a new imprinted locus, and also suggest a possible molecular basis for the
      strong bias of paternal allele mutations and variable penetrance observed in
      syndromes with inherited WT1 mutations.

PMID- 14681304
TI  - Polymorphism in the P-selectin and interleukin-4 genes as determinants of stroke:
      a population-based, prospective genetic analysis.
AB  - Candidate gene polymorphisms related to inflammation, thrombosis and lipid
      metabolism have been implicated in the development of ischemic stroke. Using DNA
      samples collected at baseline in a prospective cohort of 14 916 initially healthy
      American men, we genotyped 92 polymorphisms from 56 candidate genes among 319
      individuals who subsequently developed ischemic stroke and among 2092 individuals
      who remained free of reported cardiovascular disease over a mean follow-up period
      of 13.2 years to prospectively determine whether candidate gene polymorphisms
      contribute to stroke risk. After adjustment for multiple comparisons and age,
      smoking, body mass index, hypertension, hyperlipidemia and diabetes, two related
      to inflammation [a val640leu polymorphism in the P-selectin gene (OR=1.63, 95% CI
      1.22-2.17, P=0.001) and a C582T polymorphism in the interleukin-4 gene (OR=1.40,
      95% CI 1.13-1.73, P=0.003)] were found to be independent predictors of thrombo
      embolic stroke. In bootstrap replications, the inclusion of genetic information
      from these two polymorphisms improved prediction models for stroke based upon
      traditional risk factors alone (ROC 0.67 versus 0.64). Two polymorphisms related
      to thrombosis (an arg353gln polymorphism in the factor VII gene and a T11053G
      polymorphism in the plasminogen activator inhibitor type-1 gene) and one related
      to lipid metabolism [a C(-482)T polymorphism in the apolipoprotein CIII gene]
      achieved nominal significance, but were not found to be independent predictors
      after multiple comparison adjustment. Two inflammatory candidate gene
      polymorphisms were identified which were independently associated with incident
      stroke. These population-based data demonstrate the ability of prospective,
      epidemiological studies to test candidate gene associations for athero-thrombotic
      disease.

PMID- 14681305
TI  - The Wilms' tumour protein (WT1) shuttles between nucleus and cytoplasm and is
      present in functional polysomes.
AB  - Mutations of the Wilms' tumour-1 (WT1) gene in humans can lead to childhood
      kidney cancer, life-threatening glomerular nephropathy and gonadal dysgenesis.
      The WT1 protein is normally expressed in the developing genitourinary tract,
      heart, spleen and adrenal glands and is crucial for their development, however
      it's function at the molecular level is yet to be fully understood. The protein
      is predominantly nuclear and there is evidence that the two different isoforms of
      WT1 (-KTS and +KTS) are involved in two different steps of gene expression
      control: transcription and RNA processing. In this study we report a novel
      property of WT1, namely that it shuttles between the nucleus and cytoplasm.
      Moreover, western blot analysis showed that between 10 and 50% of total cellular
      WT1 can be detected in the cytoplasm depending on the cell type. A significant
      proportion of cytoplasmic WT1 is in association with ribonucleoprotein particles
      (RNPs), which strengthens the idea of its involvement in RNA metabolism.
      Furthermore, we report that WT1 is associated with actively translating
      polysomes, extending even further the potential roles of WT1 and opening the
      possibility that it is involved in the regulation of translation. Interestingly,
      despite the functional differences between two of the WT1 isoforms (+/-KTS)
      within the nucleus, both isoforms share the shuttling property and are found in
      translating polysomes.

PMID- 14681307
TI  - The pros and cons of publishing genetic toxicology studies in which the
      identities of the compounds are withheld.

PMID- 14681308
TI  - The restriction site mutation (RSM) method: clinical applications.
AB  - The restriction site mutation (RSM) method has been developed over the past 13
      years as a sensitive mutation test which can detect mutations in restriction
      sites in any gene. Due to the fact that 5/8 of the main mutation hotspots in the
      TP53 gene fall within restriction sites, RSM can analyse them for the presence of
      rare mutations (1 mutation in 10000 non-mutated copies). After validating the
      usefulness of RSM in detecting mutagen-induced mutations, we recently turned our
      attention to looking for TP53 mutations in pre-malignant tissue. We show here
      that RSM can detect early TP53 mutations in pre-malignant tissue of the
      oesophagus, stomach, colon and bladder. We can also use these clinical mutation
      data to speculate as to the causative mutagens involved in these cancer
      conditions. We here use an example of mutations detected in gastric tissue and
      those induced in vitro by hydrogen peroxide.

PMID- 14681306
TI  - Aberrant interchromosomal exchanges are the predominant cause of the 22q11.2
      deletion.
AB  - Chromosome 22q11.2 deletions are found in almost 90% of patients with
      DiGeorge/velocardiofacial syndrome (DGS/VCFS). Large, chromosome-specific low
      copy repeats (LCRs), flanking and within the deletion interval, are presumed to
      lead to misalignment and aberrant recombination in meiosis resulting in this
      frequent microdeletion syndrome. We traced the grandparental origin of regions
      flanking de novo 3 Mb deletions in 20 informative three-generation families.
      Haplotype reconstruction showed an unexpectedly high number of proximal
      interchromosomal exchanges between homologs, occurring in 19/20 families.
      Instead, the normal chromosome 22 in these probands showed interchromosomal
      exchanges in 2/15 informative meioses, a rate consistent with the genetic
      distance. Meiotic exchanges, visualized as MLH1 foci, localize to the distal long
      arm of chromosome 22 in 75% of human spermatocytes tested, also reflecting the
      genetic map. Additionally, we found no effect of proband gender or parental age
      on the crossover frequency. Parental origin studies in 65 de novo 3 Mb deletions
      (including these 20 patients) demonstrated no bias. Unlike Williams syndrome, we
      found no chromosomal inversions flanked by LCRs in 22 sets of parents of 22q11
      deleted patients, or in eight non-deleted patients with a DGS/VCFS phenotype
      using FISH. Our data are consistent with significant aberrant interchromosomal
      exchange events during meiosis I in the proximal region of the affected
      chromosome 22 as the likely etiology for the deletion. This type of exchange
      occurs more often than is described for deletions of chromosomes 7q11, 15q11,
      17p11 and 17q11, implying a difference in the meiotic behavior of chromosome 22.

PMID- 14681309
TI  - Preantral follicle culture as a novel in vitro assay in reproductive toxicology
      testing in mammalian oocytes.
AB  - The most common genetic disorder in humans, trisomy, is caused predominantly by
      errors in chromosome segregation during oogenesis. Isolated mouse oocytes
      resuming meiosis and progressing to metaphase II in vitro have recently been used
      to assess targets, aneugenic potential and sensitivity of oocytes to chemical
      exposures. In order to extend in vitro maturation tests to earlier stages of
      oogenesis, an in vitro assay with mouse preantral follicle cultures has been
      established. It permits the identification of direct and also indirect effects of
      environmental chemicals on the somatic compartment, the follicle and theca cells,
      that may lead to disturbances of oocyte growth, maturation and chromosome
      segregation. Early preantral follicles from prepubertal female mice are cultured
      in microdroplets for 12 days under strictly controlled conditions. The follicle
      enclosed oocytes resume maturation, develop to metaphase II and become in vitro
      ovulated within 16 h after a physiological ovulatory stimulus with recombinant
      human gonadotrophins and epidermal growth factor. These oocytes grown and matured
      in vitro possess normal barrel-shaped spindles with well-aligned chromosomes.
      Their chromosomes segregate with high fidelity during anaphase I. The model
      aneugen colchicine induced a meiotic arrest and aneuploidy in these in vitro
      grown, follicle-enclosed oocytes in a dose-dependent manner, comparable to in
      vivo tests. Therefore, preantral follicle culture appears to provide an effective
      and reliable method to assess the influences of environmental mutagens,
      pharmaceutical agents and potentially endocrine disrupting chemicals on the
      fidelity of female meiosis.

PMID- 14681310
TI  - Cytogenetic detection of a trans-species bystander effect: induction of sister
      chromatid exchanges in murine 3T3 cells by ganciclovir metabolized in HSV
      thymidine kinase gene-transfected Chinese hamster ovary cells.
AB  - Due to the very limited transduction capacity of hitherto available vectors, the
      success of gene therapy of tumours by means of suicide genes has so far
      essentially depended on the transfer of toxic drug metabolites from transduced
      (metabolizing) cells to adjacent non-transduced cells via gap junctions
      (bystander effect). Most experimental systems for the detection of a bystander
      effect yield net data of cell losses and cannot differentiate between killed
      transduced versus killed bystander cells. Here we report on metabolic cooperation
      in vitro between CHO cells stably transfected with the thymidine kinase gene of
      herpes simplex virus type-1 (HSVtk) (metabolizing cells) and Swiss albino 3T3
      cells (bystander cells). Both cell lines are readily distinguishable by single
      cell and colony morphology and by their chromosomal constitution. While 3T3 cells
      cultured alone were refractory to the antiviral drug ganciclovir (GCV), co
      culture with CHO-HSVtk(+) cells led to a dramatic reduction in plating efficiency
      as well as to a 4-fold increase in sister chromatid exchange rates induced by
      very low GCV concentrations in the 3T3 bystander cells. The modulator of gap
      junctional cooperation, all-trans retinoic acid, caused a strong augmentation of
      the bystander effect, while 18alpha-glycyrrhetinic acid, an inhibitor of gap
      junctional communication, drastically diminished the toxicity of GCV in the
      bystander cells. Whereas CHO-HSVtk(+) cells showed a distinct immunoreactivity
      for connexin43 in the cell membranes, 3T3 cells were almost negative. The co
      culture system described here allows unequivocal distinction between metabolizing
      and bystander cells. In this way, mechanistic aspects of the transfer of
      genotoxic/cytotoxic metabolites to cells, which per se are unable to form them,
      become accessible to investigation.

PMID- 14681311
TI  - Genotoxic evaluation of welders occupationally exposed to chromium and nickel
      using the Comet and micronucleus assays.
AB  - Chromium (Cr) and nickel (Ni) are widely used industrial chemicals. Welders in
      India are inclined to possible occupational Cr and Ni exposure. The carcinogenic
      potential of metals is a major issue in defining human health risk from exposure.
      Hence, in the present investigation, 102 welders and an equal number of control
      subjects were monitored for DNA damage in blood leucocytes utilizing the Comet
      assay. The two groups had similar mean ages and smoking prevalences. A few
      subjects were randomly selected for estimation of Cr and Ni content in whole
      blood by inductively coupled plasma mass spectrometry. The Comet assay was
      carried out to quantify basal DNA damage. The mean comet tail length was used to
      measure DNA damage. Welders had higher Cr and Ni content when compared with
      controls (Cr, 151.65 versus 17.86 micro g/l; Ni 132.39 versus 16.91 micro g/l; P
      < 0.001). The results indicated that the welders had a larger mean comet tail
      length than that of the controls (mean +/- SD, 23.05 +/- 3.86 versus 8.94 +/-
      3.16; P < 0.001). In addition, the micronucleus test on buccal epithelial cells
      was carried out in a few randomly selected subjects. Welders showed a significant
      increase in micronucleated cells compared with controls (1.30 versus 0.32; P <
      0.001). Analysis of variance revealed that occupational exposure (P < 0.05) had a
      significant effect on DNA mean tail length, whereas smoking and age had no
      significant effect on DNA damage. The current study suggested that chronic
      occupational exposure to Cr and Ni during welding could lead to increased levels
      of DNA damage.

PMID- 14681312
TI  - Evaluation of cytogenetic and DNA damage in mitochondrial disease patients:
      effects of coenzyme Q10 therapy.
AB  - Endogenous oxidative stress is believed to play a key role in the pathogenesis of
      mitochondrial diseases (MD). In this group of heterogeneous disorders the
      increased production of radical species caused by compromised mitochondrial
      respiratory function could affect both mitochondrial and nuclear DNA integrity.
      The aim of the present study was to assess the basal level of nuclear DNA (nDNA)
      damage in terms of chromosome and DNA alterations in leukocytes of 13 patients
      (age range 29-74 years) presenting several forms of MD. A further objective of
      this work was the evaluation of possible changes in nDNA in a subgroup of
      patients (10 individuals) before and after a 2 week therapy with ubidecarenone, a
      coenzyme Q10 analogue. The extent of cytogenetic damage, expressed as chromosome
      breakage and chromosome loss, was assessed employing the cytokinesis block
      micronucleus method in cultured peripheral blood lymphocytes, coupled with
      fluorescence in situ hybridization analysis using a digoxigenin-labelled
      pancentromeric DNA probe. A modified version of the single cell gel
      electrophoresis assay was used to quantify primary and oxidative DNA damage in
      leukocytes. In MD patients an increased level of chromosome damage, expressed as
      frequency of micronucleated lymphocytes, was detected in comparison with healthy
      individuals of corresponding sex, age and lifestyle. The FISH analysis revealed a
      preferential occurrence of micronuclei arising from loss of whole chromosomes in
      patients, with no substantial difference in frequencies observed in matched
      controls. The Comet assay indicated a slightly higher level of primary DNA damage
      in patients compared with controls and also a difference in oxidative DNA damage,
      however, this was not statistically significant. Patients receiving ubidecarenone
      showed a statistically significant reduction in the frequency of micronucleated
      cells after therapy, while only a slight decrease was observed in the levels of
      both primary DNA damage and oxidized bases.

PMID- 14681313
TI  - Use of the alkaline in vivo Comet assay for mechanistic genotoxicity
      investigations.
AB  - The alkaline Comet assay was used to investigate the in vivo genotoxicity of 17
      compounds. Altogether 21 studies were conducted with these compounds. The
      investigations were triggered for various reasons. The main reason for performing
      the studies was to evaluate the in vivo relevance of in vitro genotoxicity
      findings with 10 compounds. Eight of these compounds showed no effects in the in
      vivo Comet assay while two compounds induced altered DNA migration patterns in
      specific organs. The remaining seven compounds were tested to follow up on
      neoplastic/preneoplastic or chronic toxicity changes as detected in specific
      target organs identified in rodent studies, to investigate the possibility of
      site-of-contact genotoxicity and to test the liver as a target organ for a
      suspected reactive metabolite. For the studies, various organs of rodents were
      analyzed, depending on the suspected properties of the compounds, including
      liver, jejunum, leukocytes, stomach mucosa, duodenum, lung and kidney. All
      tissues were amenable to investigation by gel electrophoresis after simple
      disaggregation of organs by means of mincing or, in the case of epithelial cells
      from the gastrointestinal tract, scraping off cells from the epithelium. In
      conclusion, the Comet assay was found to be a reliable and robust test to
      investigate in vivo genotoxicity in a variety of rodent organs. Therefore, it is
      concluded that in vivo Comet assay data are useful for elucidating positive in
      vitro genotoxicity findings and to evaluate genotoxicity in target organs of
      toxicity.

PMID- 14681314
TI  - A 4 year follow-up analysis of genotoxic damage in birds of the Donana area
      (south west Spain) in the wake of the 1998 mining waste spill.
AB  - A total of 330 white storks (Ciconia ciconia) and 138 black kites (Milvus
      migrans) were blood sampled during four consecutive years in an area heavily
      contaminated as a consequence of a massive spillage of toxic acid mining waste
      rich in heavy metals that impacted on the Donana National Park (south western
      Spain), in April 1998. The alkaline single cell gel electrophoresis (Comet) assay
      was performed as a genotoxicity test, in order to assess whether the high level
      of DNA damage first detected by us 1 year after the disaster was still present in
      birds in each of the successive 3 years. Our results clearly show that, when
      compared with control individuals from non-polluted areas, white storks and black
      kites born in the contaminated area for a period of up to 4 years after the toxic
      accident have suffered an increase of at least 2- to 10-fold in the level of
      their genetic damage through the study period. Taken as a whole, these
      observations seem to indicate that the toxic spill still appears to be affecting
      the wildlife 4 years after the mining disaster and that attempts at cleaning up
      the waste have proved ineffective based on DNA damage detection.

PMID- 14681315
TI  - Age, sex and co-exposure to N-ethyl-N-nitrosourea influence mutations in the Alu
      repeat sequences in diethylstilbestrol-induced kidney tumors in Syrian hamsters.
AB  - We report, for the first time, mutations in the Alu repeat regions in the genome
      of kidney tumors induced by diethylstilbestrol in Syrian hamsters. Among the 66
      loci amplified by 11 random primers, 28 loci exhibited insertions, deletions or
      losses or gains in intensity in the genome of kidney tumor tissues compared with
      normal kidney tissues from age-matched hamsters. Higher numbers of mutated Alu
      loci were observed in the tumors of old hamsters compared with young hamsters. In
      N-ethyl-N-nitrosourea- and diethylstilbestrol-treated hamsters deletion of a 0.59
      kb locus amplified with primer OPC03 was observed in most of the female hamsters,
      but not in male hamsters. An insertion mutation of a 0.498 kb locus amplified
      with primer OPC03 was observed in 12 of 36 diethylstilbestrol-induced kidney
      tumors. The cloning and sequencing of the 0.498 kb locus amplified with primer
      OPC03 revealed that it had significant sequence similarity to the mouse RIKEN
      cDNA clone. These findings indicate that age, sex and co-exposure to N-ethyl-N
      nitrosourea influence mutations in the Alu repeat sequences in the genome of
      diethylstilbestrol-induced kidney tumors in Syrian hamsters. Structural
      alterations in Alu repeats in critical target genes may be involved in
      diethylstilbestrol-induced carcinogenesis.

PMID- 14681316
TI  - In vitro genotoxicity testing of the furylethylene derivative UC-245 in human
      cells.
AB  - The possible genotoxic potential of the 2-furylethylene derivative UC-245 has
      been evaluated in vitro using human cells as a test system. This compound was
      synthesized at the Centro de Bioactivos Quimicos, Universidad Central de Las
      Villas (Cuba) and it appears to be effective against leishmaniosis. The induced
      genetic damage was determined by scoring the frequency of micronuclei (MN) and
      the frequency of sister chromatid exchanges (SCE) in primary lymphocyte cultures
      set up from two different donors. The DNA breakage level was also evaluated by
      the Comet assay, using an established human lymphoblastoid cell line (TK6). For
      the MN and SCE studies, to detect eventual metabolic modification in the
      genotoxicity of this compound, the cultures were treated with S9 microsomal
      fraction. The results obtained indicate that, under the experimental conditions
      used, the test agent does not induce significant increases in the frequency of
      micronucleated cells, irrespective of presence/absence of the metabolic fraction,
      which would indicate a lack of clastogenic and/or aneugenic potential.
      Nevertheless, a clear and significant increase in the SCE frequency was observed
      in the treatments without S9. This would support the 2-furylethylene derivative
      UC-245 inducing DNA primary damage. In addition, the results obtained in the
      Comet assay also show that UC-245 induces a significant increase in the level of
      DNA breakage, which would confirm its genotoxicity.

PMID- 14681317
TI  - Validation of tissue microarrays using p53 immunohistochemical studies of
      squamous cell carcinoma of the larynx.
AB  - Tissue microarrays are a powerful new tissue-conserving technology in the study
      of cancer, allowing simultaneous study of a large number of tumor specimens. We
      sought to ascertain the utility of tissue microarrays in head and neck cancer
      pathology using squamous cell carcinoma of the larynx as a model system. Whole
      specimen slides from 44 different laryngeal squamous cell carcinomas were stained
      for p53 expression. Microarrays were then generated by taking six 0.6-mm core
      biopsies from each of the 44 specimens. The whole sections and the microarrays
      were independently scored for p53 expression. Twenty-three (53%) of the 44 tumor
      specimens were positive for p53. Forty-four of the 264 core biopsies (17%) were
      not given a score because of the lack of tumor cells. Seventy-eight percent of
      the individual discs on the microarray had scores in agreement with those of the
      whole-section slides. Among biopsy discs with tumor cells present, 94.5% were in
      agreement with the whole-section slide. The average probability that four
      randomly chosen biopsy discs, considered together, would accurately identify the
      presence of p53 staining in a whole section was 0.97 (95% CI.93-1.0). We conclude
      that tissue microarrays for squamous cell carcinomas can accurately represent
      immunohistochemical results of whole-slide specimens when four or more samples
      are used. Tissue microarrays are an important technique that may be applied to
      immunohistochemical studies of head and neck cancer.

PMID- 14681318
TI  - Genetic alterations in goblet cell carcinoids of the vermiform appendix and
      comparison with gastrointestinal carcinoid tumors.
AB  - Goblet cell carcinoid is a relatively rare neuroendocrine tumor of the vermiform
      appendix with poorly understood molecular pathogenesis. We studied the
      clinicopathologic features and genetic alterations, including allelic loss of
      chromosomes 11q, 16q, and 18q; sequencing of the K-ras, beta-catenin, and DPC4
      (SMAD4) genes; and p53 overexpression and loss of DPC4 by immunohistochemistry;
      in 16 goblet cell carcinoids. We compared the allelic loss in goblet cell
      carcinoids to those in 18 gastrointestinal carcinoid tumors. For goblet cell
      carcinoids, appendiceal perforation was the most common (70%, 7/10) clinical
      presentation. The mean tumor size was 2.0 +/- 1.5 cm (range, 0.4 to 4.5 cm). The
      tumor invaded to appendiceal serosa in 50% (8/16) of patients, and two patients
      had metastasis in lymph nodes or adjoining viscera. With mean follow-up of 24 +/-
      14 months (median, 23 mo), 1 of 10 patients had died of disease, and 2 others had
      tumor recurrence. All four patients with metastases, recurrences, and/or death
      from disease had serosal involvement at presentation (P =.02). Loss of
      heterozygosity of chromosome 11q was present in 25% of goblet cell carcinoids,
      14% of ileal carcinoid tumors, and 9% of nonileal carcinoid tumors; of chromosome
      16q in 38%, 29%, and 0 (P =.02); and of chromosome 18q in 56%, 86%, and 9% (P
      =.002), respectively. No mutations of K-ras, beta-catenin, or DPC4 genes; p53
      overexpression; or loss of staining for DPC4 was present in any tumors. These
      findings suggest that allelic loss of chromosomes 11q, 16q, and 18q in goblet
      cell carcinoids and ileal carcinoids may have an important role in the
      pathogenesis of these tumors.

PMID- 14681320
TI  - Alpha-inhibin immunoreactivity in soft-tissue neoplasia.
AB  - Antibodies directed against alpha-inhibin have been previously reported as
      staining both sex cord-stromal neoplasms as well as adrenal cortical tumors. This
      relatively restricted immunoreactivity pattern is useful in the assessment of
      retroperitoneal masses, especially in a setting of limited tissue (e.g., needle
      biopsy). However, no study to date has evaluated alpha-inhibin immunoreactivity
      in soft-tissue neoplasms, which frequently enter the differential diagnosis of
      retroperitoneal masses. We investigate the incidence of alpha-inhibin staining in
      a variety of soft-tissue neoplasms by using formalin-fixed, paraffin-embedded
      tissue sections from 282 previously classified soft-tissue neoplasms with anti
      alpha-inhibin (Serotec, 1:75). A modified avidin-biotin complex method was used
      after heat-induced epitope retrieval. Cytoplasmic granular staining was
      considered positive. Of the 282 tumors studied, a total of 8 (2.8%) demonstrated
      positive staining with anti-alpha-inhibin antibody. These included 4 of 25
      liposarcomas (16%), 2 of 18 angiosarcomas (11%), 1 of 48 lipomas (2.1%), and 1 of
      1 rhabdomyoma (100%). Negative staining was noted among hemangiomas (0/28),
      schwannomas (0/32), leiomyomas (0/16), fibrosarcomas (0/2), fibromas (0/11),
      dermatofibromas (0/9), neurofibromas (0/6), synovial sarcomas (0/15),
      rhabdomyosarcomas (0/10), Triton tumors (0/2), and malignant fibrous
      histiocytomas (0/59). We conclude that rare soft-tissue tumors, especially those
      exhibiting either lipomatous or vascular differentiation, demonstrate alpha
      inhibin immunoreactivity. These findings re-emphasize the need for a well
      construed antibody panel when immunohistochemical methods are employed in the
      evaluation of retroperitoneal neoplasms. However, the rarity of alpha-inhibin
      expression by soft-tissue neoplasms provides further support for its overall
      specificity as a marker of adrenal cortical differentiation in the biopsy
      evaluation of a retroperitoneal mass.

PMID- 14681319
TI  - Overexpression of cyclooxygenase-2 is associated with breast carcinoma and its
      poor prognostic factors.
AB  - Cyclooxygenase is the rate-limiting enzyme that catalyzes the conversion of
      arachidonic acid to prostaglandins. The inducible form, cyclooxygenase-2, is
      known to be overexpressed in various human cancers including the colon, stomach,
      and urinary bladder. In this study, we evaluated the overexpression of
      cyclooxygenase-2 in 64 cases of breast cancer and correlated the results with
      clinicopathologic parameters. Immunohistochemical staining for cyclooxygenase-2
      demonstrated positivity of the tumor cells in 46 of 64 cases (72%).
      Cyclooxygenase-2 overexpression was significantly correlated with larger tumor
      size and advanced clinical stage. Cyclooxygenase-2 overexpression tended to be
      more frequently observed in cases with presence of lymph node metastasis and in
      cases without expression of estrogen and progesterone; however, there was no
      significant correlation statistically. Nuclear and histologic grade were not well
      correlated with cyclooxygenase-2 overexpression. When ductal carcinoma in situ
      was considered separately, 32 of 42 cases (76%) were positive for cyclooxygenase
      2. We conclude that cyclooxygenase-2 is up-regulated in a high proportion of
      breast cancers. The overexpression of cyclooxygenase-2 was associated with larger
      tumor size and advanced clinical stage, although lymph node status, estrogen and
      progesterone expression, and nuclear and histologic grade were not significantly
      correlated. Therefore, cyclooxygenase-2 overexpression may be a feature of the
      aggressive phenotype and may be useful as a prognostic indicator in breast
      cancer.

PMID- 14681321
TI  - Splenic marginal zone lymphomas presenting with splenomegaly and typical
      immunophenotype are characterized by allelic loss in 7q31-32.
AB  - Splenic marginal zone lymphoma (SMZL) is a rare non-Hodgkin's lymphoma that
      recently has been recognized as an entity. The first goal of this study was to
      identify potential chromosomal aberrations in this entity by cytogenetic analysis
      and comparative genomic hybridization (CGH). The second goal was to assess the
      frequency of 7q31-32 allelic imbalances in SMZL with primary involvement of the
      spleen and the typical immunophenotype (IgM+; IgD(dim); and CD5-, CD10-, and CD23
      ). We applied CGH and cytogenetics to 13 cases of SMZL with primary splenic
      involvement. By CGH, we found DNA copy number changes in 11 of 13 cases. Overall
      chromosomal gains were more frequent than chromosomal losses. Gains were most
      frequently detected for chromosome X, chromosome 3, and chromosome 18. Losses
      commonly involved chromosome 7 and chromosome 6.CGH and cytogenetic analysis
      showed a deletion in chromosome 7q31 in 4 cases. Loss of heterozygosity (LOH)
      analysis using three microsatellite markers located at 7q31 revealed LOH in 9
      cases. Remarkably, 2 of the 4 cases that lacked a 7q31 deletion had an atypical
      immunophenotype because they were partially CD23 positive. The other 2 cases were
      not informative. The findings indicate that SMZL with primary splenic
      presentation and the typical IgM+, IgDdim, CD5-, CD10-, CD23- immunophenotype is
      characterized by the presence of deletions in chromosome 7q31-32.

PMID- 14681322
TI  - Expression of peroxisome proliferator-activated receptor gamma in salivary duct
      carcinoma: immunohistochemical analysis of 15 cases.
AB  - Salivary duct carcinoma is a rare but highly aggressive tumor of the salivary
      glands that has poor prognosis. There is no effective cure for this tumor.
      Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the
      nuclear receptor family with diverse biological functions that include mediation
      of adipocyte differentiation, regulation of the monocyte-macrophage anti
      inflammatory activity, and inhibition of tumor cell proliferation. Natural
      (prostaglandin J2, PG-J2) and synthetic (thiazolinediones) PPARgamma ligands with
      anti-proliferative agonist activity have been identified. The expression of
      PPARgamma has been demonstrated in human colorectal, pancreas, breast, and
      prostate cancers but has never been explored in salivary duct carcinoma. The aim
      of our study was to investigate the expression patterns of PPARgamma in salivary
      duct carcinoma, a finding that may provide a mechanism for treating patients with
      this highly aggressive tumor. Archival formalin-fixed tissues from 15 salivary
      duct carcinoma cases were analyzed for PPARgamma expression by an
      immunohistochemical staining method using a monoclonal antibody against the
      PPARgamma. The tissue sections were subjected to antigen retrieval by a steam
      heat method. All the cases of salivary duct carcinoma originated from the parotid
      gland. Immunohistochemistry analyses showed positive expression of PPARgamma in
      12 (80%) cases, whereas 3 (20%) were negative. Of the positive cases, 9 (75%), 2
      (17%) and 1 (8%) showed strong, moderate, and weak staining, respectively. All
      staining was cytoplasmic. Nuclear staining was not observed. We conclude that
      PPARgamma is frequently (80%) expressed in salivary duct carcinoma, often at high
      levels, and is topographically located in the cytoplasm. The high-level
      expression of PPARgamma may provide a potential molecular target for the
      treatment of salivary duct carcinoma using agonist ligands.

PMID- 14681323
TI  - Expression of KIT (CD117) in neoplasms of the head and neck: an ancillary marker
      for adenoid cystic carcinoma.
AB  - Adenoid cystic carcinoma is an indolent salivary gland malignancy that is
      associated with a poor long-term prognosis. The distinction of adenoid cystic
      carcinoma from other head and neck neoplasms can occasionally be problematic,
      particularly in small biopsies. Recent studies suggest that KIT (CD117) might be
      useful as an ancillary marker for adenoid cystic carcinoma; however, the
      expression of KIT in other benign and malignant head and neck neoplasms,
      including those that might mimic adenoid cystic carcinoma, has not been well
      studied. Here we use two different antibodies against KIT to evaluate its
      expression in a series of 66 adenoid cystic carcinomas compared with its
      expression in 98 other neoplasms of the head and neck. Overall, 94% (n = 62) of
      adenoid cystic carcinomas from various anatomic sites and of various histologic
      subtypes were positive for at least one of the KIT antibodies, and 77% (n = 50)
      of adenoid cystic carcinoma cases were positive for both antibodies. This
      contrasted with only 8% (n = 8) of other head and neck neoplasms that were
      positive for both KIT antibodies (P <.001). It was of note that certain
      neoplasms, including pleomorphic adenoma, basal cell adenoma, polymorphous low
      grade adenocarcinoma, and basal cell carcinoma, that can show histologic overlap
      with adenoid cystic carcinoma had significantly less KIT immunoreactivity than
      did adenoid cystic carcinoma (P <.001). In contrast, KIT expression did not
      reliably distinguish adenoid cystic carcinoma from basal cell adenocarcinoma and
      basaloid squamous carcinoma (P >.05). The overall sensitivity of the two KIT
      antibodies for adenoid cystic carcinoma was 82-89%, and the specificity was 87
      88%. The findings in this study support the potential use of KIT immunoexpression
      for distinguishing adenoid cystic carcinoma from many other benign and malignant
      head and neck neoplasms.

PMID- 14681324
TI  - API2-MALT1 fusion gene in colorectal lymphoma.
AB  - The API2-MALT1 fusion gene was originally identified from a t(11;18)(q21;q21)
      translocation, a specific chromosomal abnormality that is found in mucosa
      associated lymphoid tissue (MALT) lymphoma. Gastric MALT lymphomas positive for
      the API2-MALT1 fusion gene do not respond to Helicobacter pylori-eradication
      therapy, but otherwise, the incidence and clinicopathological behavior of
      colorectal MALT lymphoma with this genetic abnormality are unclear. We examined
      the API2-MALT1 fusion by multiplex RT-PCR method in 47 cases of MALT lymphoma and
      13 cases of diffuse large B-cell lymphoma and evaluated the relevance of API2
      MALT1 positivity to the clinical and pathological features. The mean ages of MALT
      lymphoma and diffuse large B-cell lymphoma patients were 65 (range, 37-87 y) and
      58 (range, 14-85 y) years, respectively. API2-MALT1 fusion genes were detected in
      seven cases (15%) of MALT lymphoma and one case (8%) of diffuse large B-cell
      lymphoma. In MALT lymphomas, the tumor size in API2-MALT1-positive cases was 62
      +/- 39 mm (mean +/- SD), statistically larger than that in API2-MALT1-negative
      cases (25 +/- 19 mm; P <.01). The API2-MALT1-positive cases demonstrated more
      advanced clinical stages and a male predominance, compared with API2-MALT1
      negative cases. Thus, API2-MALT1-positive tumors should be cared for as a more
      aggressive subgroup and be followed for a longer time.

PMID- 14681325
TI  - Epstein-Barr virus infection is not associated with fibroadenomas of the breast
      in immunosuppressed patients after organ transplantation.
AB  - Epstein-Barr virus has been linked to an increasing number of nonhematolymphoid
      conditions. Epstein-Barr virus was recently described in association with
      fibroadenomas of the breast occurring in immunosuppressed patients. To further
      investigate the potential association of Epstein-Barr virus with fibroadenoma in
      the context of immune dysfunction, 11 cases of fibroadenoma of the breast in
      immunosuppressed organ transplant recipients were examined. Cases were evaluated
      for the presence of Epstein-Barr virus by polymerase chain reaction, in situ
      hybridization, and immunohistochemical methods. The presence of Epstein-Barr
      virus genomic DNA was studied by polymerase chain reaction amplification using
      primers flanking the BamHI-W fragment of the Epstein-Barr virus genome, as well
      as the Epstein-Barr virus nuclear antigen-4 and latent membrane protein-1 genes.
      Cases were also evaluated for the presence of defective heterogeneous Epstein
      Barr virus DNA. In addition, morphologic analysis by in situ hybridization for
      Epstein-Barr virus-encoded RNA-1 and immunohistochemistry for latent membrane
      protein-1 were performed. Epstein-Barr virus DNA was detected in 4 of 11 (36%)
      cases with BamHI-W polymerase chain reaction. Polymerase chain reaction studies
      for Epstein-Barr virus nuclear antigen-4 and latent membrane protein-1 genes were
      positive in two and four cases, respectively. No defective Epstein-Barr virus
      genomes were identified in any of the cases. Quantitative polymerase chain
      reaction demonstrated low levels of Epstein-Barr virus in the fibroadenomas
      studied. Despite the detection of Epstein-Barr virus genomes in a subset of the
      cases examined, the constituent epithelial and stromal components of all
      fibroadenomas demonstrated no evidence of Epstein-Barr virus-encoded RNA-1 by in
      situ hybridization or latent membrane protein-1 expression by
      immunohistochemistry. Rare Epstein-Barr virus-encoded RNA-1-positive lymphocytes
      were observed in some cases, which may account for the positive polymerase chain
      reaction results. The findings of the present study argue against a significant
      relationship between Epstein-Barr virus and fibroadenomas of the breast in the
      setting of transplant-associated immunosuppression.

PMID- 14681326
TI  - Detection of single-copy chromosome 17q gain in human neuroblastomas using real
      time quantitative polymerase chain reaction.
AB  - Regional genomic alterations resulting from single-copy allelic loss or gain have
      been well characterized in many human cancers and are often of prognostic
      relevance. Unbalanced gain of 17q material is common in malignant human
      neuroblastomas and typically results from unbalanced translocations. Unbalanced
      17q gain may be an independent predictor of disease outcome, but technical
      difficulties with quantifying such gain using fluorescent in situ hybridization
      gives this method limited clinical applicability. We now describe a duplex
      genomic DNA-based quantitative polymerase chain reaction assay to determine the
      presence or absence of unbalanced gain of chromosome 17q in primary neuroblastoma
      specimens. The technique was first refined and validated in a panel of nine human
      neuroblastoma-derived cell lines by direct comparison with dual-color fluorescent
      in situ hybridization. Prospective blinded comparison of quantitative polymerase
      chain reaction and fluorescence in situ hybridization in 40 human neuroblastoma
      primary tumor samples showed a sensitivity of 96% and 100% specificity for
      detecting unbalanced 17q gain when a relative 17q copy number ratio of 1.3 was
      used to define unbalanced gain. Tumors with ratios >1.3 were highly associated
      with malignant tumor phenotypic features such as metastatic disease (P <.0001)
      and tumor MYCN amplification (P =.008). These data suggest that quantitative
      polymerase chain reaction determination of 17q status is feasible and highly
      specific in primary tumor samples. Sensitivity may be limited because of the
      inherent complexity of both the chromosomal rearrangements and heterogeneity of
      some tumor samples. Taken together, quantitative polymerase chain reaction can be
      used as a high-throughput screening tool for 17q aberrations, but a subset of
      samples may also require fluorescence in situ hybridization analysis in an
      attempt to conclusively determine 17q allelic status.

PMID- 14681327
TI  - Gastrointestinal stromal tumors with internal tandem duplications in 3' end of
      KIT juxtamembrane domain occur predominantly in stomach and generally seem to
      have a favorable course.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. GISTs express KIT and have KIT mutations. Majority of
      these mutations cluster in the 5' end of the KIT juxtamembrane domain. Little is
      known about the clinicopathological profile of GIST carrying internal tandem
      duplications in the 3' end of KIT juxtamembrane domain (ITDs in the 3' KIT-JM).
      In this study, 500 immunohistochemically KIT-positive GISTs were screened for
      this type of mutation, and 18 cases were identified (3.6%). The majority of the
      ITDs consisted of 1 to 18 codon duplications, with Tyr(578), Asp(579), and
      Leu(576) being the most commonly duplicated codons. There were 14 gastric (78%),
      2 small intestinal (11%), and 2 anal (11%) primary tumors diagnosed in 12 females
      and 6 males with median age of 71 years. The frequency of IDTs in gastric GISTs
      was 6.5% and was only 0.5% in intestinal GISTs. There was a strong female
      predominance (79%) among the patients with gastric tumors. Histologically, 16
      GISTs were spindle cell, and 2 had epithelioid morphology. The sizes of primary
      tumors varied from 1 to >20 cm. Based on the combination of tumor size and
      mitotic activity, six tumors were classified as benign or probably benign, eight
      as having uncertain malignant potential, and only four as malignant. Follow-up
      data available in 17 patients confirmed the malignant course of disease in 3
      cases. Only one of the tumors classified as potentially malignant metastasized,
      although the follow-up was limited in some cases. In summary, the great majority
      of GISTs with ITDs in the 3' KIT-JM were mitotically inactive tumors occurring
      predominantly in the stomach and that seemed to have a favorable course. This
      suggests that presence of these IDTs may define a clinicopathologically favorable
      subset of GISTs. The consequence of these mutations to KIT signaling should be
      investigated.

PMID- 14681328
TI  - Dedifferentiated adenoid cystic carcinoma: a clinicopathologic study of 6 cases.
AB  - Dedifferentiated adenoid cystic carcinomas are a recently defined, rare variant
      of adenoid cystic carcinomas characterized histologically by two components:
      conventional low-grade adenoid cystic carcinoma and high-grade "dedifferentiated"
      carcinoma. We examined six cases and analyzed their clinicopathologic profiles,
      including immunohistochemical features and p53 gene alterations. The 6 patients
      (3 men and 3 women) had a mean age of 46.8 years (range, 34-70 y). The mean size
      of the tumors was 3.5 cm (range, 1.7-6 cm). The submandibular gland, maxillary
      sinus, and nasal cavity were involved in 2 cases each. Postoperatively, 5
      patients had local recurrence and 5 developed metastatic disease. Five patients
      died of disease at a mean of 33.7 months after diagnosis (range, 6-69 mo), and
      one other was alive with disease at 60 months. Histologically, the conventional
      low-grade adenoid cystic carcinoma component of the tumors consisted of a mixture
      of cribriform and tubular patterns with scant solid areas. The high-grade
      dedifferentiated carcinoma component was either a poorly differentiated
      adenocarcinoma (4 cases) or undifferentiated carcinoma (2 cases). Three tumors
      were studied immunohistochemically. Myoepithelial markers were expressed in low
      grade adenoid cystic carcinoma but not in the dedifferentiated component. In 2
      cases, diffusely positive p53 immunoreactivity together with HER-2/neu
      overexpression was restricted to the dedifferentiated component. Loss of pRb
      expression was demonstrated only in the dedifferentiated component of the 1 other
      case. The Ki-67-labeling index was higher in the dedifferentiated component than
      in the low-grade adenoid cystic carcinoma component. Furthermore, molecular
      analysis of 2 cases demonstrated the loss of heterozygosity at p53 microsatellite
      loci, accompanied by p53 gene point mutation, only in the dedifferentiated
      carcinoma component of 1 case, which was positive for p53 immunostaining. These
      results indicate that dedifferentiated adenoid cystic carcinoma is a highly
      aggressive tumor. Because of frequent recurrence and metastasis, the clinical
      course is short, similar to that of adenoid cystic carcinomas with a predominant
      solid growth pattern. Limited evidence suggests that p53 abnormalities in
      combination with HER-2/neu overexpression or loss of pRb expression may have a
      role in dedifferentiation of adenoid cystic carcinoma.

PMID- 14681329
TI  - Potential role of bcl-2 and bax mRNA and protein expression in chronic hepatitis
      type B and C: a clinicopathologic study.
AB  - Bcl-2 oncoprotein regulates programmed cell death by providing a survival
      advantage to rapidly proliferating cells, and bax protein promotes apoptosis by
      enchanting cell susceptibility to apoptotic stimuli. In this study, we assessed
      the expression of bcl-2 and bax in liver biopsies from patients with chronic
      hepatitis (CH) Type B (HBV) and C (HCV). The study comprised 65 liver biopsies
      from 65 patients with HBV (n = 37) and HCV (n = 28) and 10 normal liver biopsies
      as controls. The HAI score ranged from 3/18-13/18, and the fibrosis Stage, from 1
      6 (7 HBV/10 HCV). Pathologic examination included the following: (1)
      immunohistochemical stains in paraffin sections for bcl-2 and bax protein
      expression, (2) Western blot analysis (bcl-2 and bax protein levels evaluation),
      (3) ISH (detection of bcl-2 and bax mRNA), and (4) ISH (TUNEL-ABI [apoptotic body
      index]). In CH cases, both bcl-2 and bax protein and mRNA were detected in portal
      and intralobular lymphocytes and in cholangiolar epithelial cells in interface
      areas and fibrous bands. Bax protein and mRNA was expressed within hepatocytes
      and epithelial cells of interlobular ducts in portal tracts. Bcl-2 mRNA was
      present in periportal hepatocytes only in cases with Stage 5-6 fibrosis. Western
      blot analysis showed a decreased bcl-2 and an increased bax expression toward
      advanced fibrotic stages. In CH cases, ABI was reverse correlated with the
      percentage of bcl-2 expression and was correlated directly with the percentage of
      bax expression (P <.001). The results of this study suggest that in cases of
      chronic HBV or HCV infection, bax may be involved in the hepatocyte cycle
      regulation during infection, whereas its expression in intraportal bile duct
      epithelium implies that this protein enhances susceptibility of these particular
      cells to apoptosis. The increased bax expression and ABI in fibrosis Stages 1-5,
      imply that they are responsible for hepatocytes depletion through apoptosis,
      during progress of liver fibrosis and fibrous tissue accumulation, until
      cirrhosis is established. Bcl-2 mRNA expression in periportal hepatocytes only in
      Stages 5 and 6 suggests that this oncogene is involved in the late stages of
      progressive liver fibrosis and failure and furthermore that periportal
      hepatocytes are resistant to apoptosis. Bcl-2 expression, in cholangioles of
      interface area, suggests that this oncoprotein may be involved in growth
      regulation of these epithelial cells. Further research is warranted to specify
      the exact role of apoptosis and apoptotic genes involved in liver fibrosis
      process in cases of chronic HBV and HCV infection. This may lead to new
      strategies in the management of human liver disease to prevent the progression to
      chronic liver failure.

PMID- 14681330
TI  - Nested variant of urothelial carcinoma: a clinicopathologic and
      immunohistochemical study of 12 cases.
AB  - Nested variant of urothelial carcinoma is characterized by confluent small nests
      and abortive tubules of mildly atypical neoplastic cells infiltrating the lamina
      propria and/or muscularis propria of the bladder. Despite its deceptively bland
      histomorphologic appearance, the lesion is reported to have an aggressive
      behavior. The collective immunohistochemical expression of suppressor genes,
      growth factor, and proliferation activity marker has not been previously studied
      in this disease. Formalin-fixed, paraffin-embedded archival tissues from 12 cases
      of nested variant of urothelial carcinoma were stained with monoclonal antibodies
      to p21, p27, p53, EGF-R, and bcl-2, as well as the proliferation marker MIB-1.
      The area of predominant immunoreactivity was also evaluated. The pattern of
      immunostaining was compared with the clinical parameters. p21 was positive in 10
      of 12 cases and located at the deepest portion of the tumor in 5 of 10 positive
      cases. Immunoreactivity for p27 was seen in 11 of 12 cases and limited to the
      superficial portion of the tumor in 9 of 11 positive cases. Only 3 and 2 of 12
      cases were positive for p53 and bcl-2, respectively. MIB-1 immunoreactivity
      ranged from 2 to 35% of the neoplastic cells, with most tumors showing a
      proliferation index of >15%. Follow-up ranged from 3 to 30 months (mean, 17.6
      mo). All patients except one were alive, although three patients developed
      metastases. Nested variant of urothelial carcinoma is a deceptively benign
      appearing neoplasm with potential of deep invasion and metastases.
      Immunohistochemically, nested variant of urothelial carcinoma shares some
      features with high-risk conventional urothelial carcinomas, such as loss of p27
      expression and high proliferation index. Nevertheless, p53, bcl-2, or EGF-r
      immunoreactivity is not frequently seen.

PMID- 14681331
TI  - Correspondence re: Bryant-Greenwood P, Sorbara L, Filie AC, Little R, Yarchoan R,
      Wilson W, Raffeld M, Abati A. Infection of mesothelial cells with human herpes
      virus 8 in human immunodeficiency virus-infected patients with Kaposi's sarcoma,
      Castleman's disease, and recurrent pleural effusions. Mod pathol 2003;16:145-53.

PMID- 14681332
TI  - Equalization of synaptic efficacy by activity- and timing-dependent synaptic
      plasticity.
AB  - In many neurons, synapses increase in strength as a function of distance from the
      soma in a manner that appears to compensate for dendritic attenuation. This
      phenomenon requires a cooperative interaction between local factors that control
      synaptic strength, such as receptor density and vesicle release probability, and
      global factors that affect synaptic efficacy, such as attenuation and boosting by
      active membrane conductances. Anti-spike-timing-dependent plasticity, in
      combination with nonassociative synaptic potentiation, can accomplish this feat
      even though it acts locally and independently at individual synapses. Analytic
      computations and computer simulations show that this combination of synaptic
      plasticity mechanisms equalizes the efficacy of synapses over an extended
      dendritic cable by adjusting local synaptic strengths to compensate for global
      attenuation.

PMID- 14681333
TI  - Body scheme gates visual processing.
AB  - We used functional magnetic resonance imaging (fMRI) to explore how guidance of
      motor acts is influenced by the visually perceived body scheme. We found that
      when subjects view their hand as their opposite hand, i.e., the right hand is
      seen as the left hand and vice versa, activation in the visual cortex was
      lateralized opposite to the seen hand. This demonstrates for the first time that
      our body scheme to which vision relates our environment is already represented at
      the level of visual cortex.

PMID- 14681334
TI  - Responses of cerebellar interpositus neurons to predictable perturbations applied
      to an object held in a precision grip.
AB  - Two monkeys were trained to lift and hold an instrumented object at a fixed
      height for 2.5 s using a precision grip. The device was equipped with load cells
      to measure both the grip and lifting or load forces. On selected blocks of 20-30
      trials, a downward force-pulse perturbation was applied to the object after 1.5 s
      of stationary holding. The animals were required to resist the perturbation to
      obtain a fruit juice reward. The perturbations invariably elicited a reflex-like,
      time-locked increase in grip force at latencies between 50 and 100 ms. In this
      study, we searched for single cells in the interpositus and dentate nuclei with
      activity related to grasping and lifting, and we tested 127/150 task-related
      cells for their responses to the perturbation. Of the 127 cells, reflex-like
      increases or decreases in discharge frequency occurred in 75 cells (59%) at a
      mean latency of 36 ms. Preparatory increases in grip force preceding the
      perturbation appeared gradually and increased in strength with repetition in
      39/127 (31%) cells. These preparatory increases did not immediately disappear
      when the perturbations were withdrawn but decreased progressively over repeated
      trials. Although a few cells showed anticipatory activity without a reflex-like
      response (15/127 or 12%), the majority of these cells (24/39) displayed both
      anticipatory and reflex-like responses. From an examination of the histological
      sections, cells with both anticipatory and reflex-like responses appeared to be
      confined to the dorsal anterior interpositus, adjacent to, but not within, the
      dentate nucleus. These results confirm and extend the suggestion by Dugas and
      Smith that the cerebellum plays a major role in organizing anticipatory responses
      to predictable perturbations in a manner that medial and lateral premotor areas
      of the cerebral cortex do not.

PMID- 14681335
TI  - Effects of muscimol inactivation of the cerebellar nuclei on precision grip.
AB  - A single monkey was trained to perform a grasp, lift, and hold task in which a
      stationary hand- held object was sometimes subjected to brief, predictable force
      pulse perturbations. The displacement, grip, and lifting forces were measured as
      well the three-dimensional forces and torques to quantify specific motor deficits
      after reversible inactivation of the cerebellar nuclei. A prior single-cell
      recording study in the same monkey provided the stereotaxic coordinates used to
      guide intranuclear injections of muscimol. In total, 34 penetrations were
      performed at 28 different loci throughout the cerebellar nuclei. On each
      penetration, two 1.0-microl injections of 5 microg/microl muscimol, were made 1.0
      mm apart either within the nuclei or in the white matter just lateral or
      posterior to the dentate nucleus. Injections in the region corresponding to the
      anterior interpositus nucleus produced pronounced dynamic tremor and dysmetric
      movements of the ipsilateral arm when the animal performed unrestrained reaching
      and grasping movements. In contrast, no relatively short-latency (15-20 min.)
      deficits were observed after injection in the dentate nucleus, although some
      effects were observed after several hours. When tested in a primate chair with
      the forearm supported and restrained at the wrist and elbow, the monkey performed
      the lift and hold task without tremor or dysmetria. However, with the restraint
      removed, the forces and torques applied to the manipulandum were poorly
      controlled and erratic. The monkey's arm was ataxic and a 5-Hz intention tremor
      was clearly visible. In addition, the animal was generally unable to compensate
      for the predictable perturbations and the anticipatory grip force increases were
      absent. However, overall the results suggest that reversible cerebellar nuclear
      inactivation with muscimol has little effect on isolated distal movements of the
      wrist and fingers.

PMID- 14681336
TI  - Spontaneous waves in the ventricular zone of developing mammalian retina.
AB  - Spontaneous rhythmic waves in the developing mammalian retina are thought to
      propagate among differentiated neurons in the inner retina (IR) and play an
      important role in activity-dependent visual development. Here we report a new
      form of rhythmic Ca(2+) wave in the ventricular zone (VZ) of the developing
      rabbit retina. Ca(2+) imaging from two-photon optical sections near the
      ventricular surface of the whole-mount retina showed rhythmic Ca(2+) transients
      propagating laterally as waves. The VZ waves had a distinctively slow Ca(2+)
      dynamics (lasting approximately 20 s) but shared a similar frequency and
      propagation speed with the IR waves. Simultaneous Ca(2+) imaging in VZ and multi
      electrode array recording in the ganglion cell layer (GCL) revealed close
      spatiotemporal correlation between spontaneous VZ and IR waves, suggesting a
      common source of initiation and/or regulation of the two waves. Pharmacological
      studies further showed that all drugs that blocked IR waves also blocked VZ
      waves. However, the muscarinic antagonist atropine selectively blocked VZ but not
      IR waves at this developmental stage, indicating that IR waves were not dependent
      on VZ waves, but VZ waves likely relied on the initiation of IR waves. Eliciting
      IR waves with puffs of nicotinic or non-N-methyl-d-aspartate agonists in GCL
      produced atropine-sensitive waves in the VZ, demonstrating a unique, retrograde
      signaling pathway from IR to VZ. Thus differentiated neurons in the IR use
      spontaneous, rhythmic waves to send both forward signals to the central visual
      targets and retrograde messages to the developing cells in the VZ.

PMID- 14681337
TI  - Human liver aldehyde oxidase: inhibition by 239 drugs.
AB  - The authors tested 239 frequently used drugs and other compounds for their
      potential to inhibit the drug-metabolizing enzyme, aldehyde oxidase, in human
      liver cytosol. A sensitive, moderate throughput HPLC-MS assay was developed for 1
      phthalazinone, the aldehyde oxidase-catalyzed product of phthalazine oxidation.
      Inhibition of this activity was examined for the 239 drugs and other compounds of
      interest at a test concentration of 50 microM. Thirty-six compounds exhibited
      greater than 80% inhibition and were further examined for measurement of IC50.
      The most potent inhibitor observed was the selective estrogen receptor modulator,
      raloxifene (IC50=2.9 nM), and tamoxifen, estradiol, and ethinyl estradiol were
      also potent inhibitors. Other classes of drugs that demonstrated inhibition of
      aldehyde oxidase included phenothiazines, tricyclic antidepressants, tricyclic
      atypical antipsychotic agents, and dihydropyridine calcium channel blockers,
      along with some other drugs, including loratadine, cyclobenzaprine, amodiaquine,
      maprotiline, ondansetron, propafenone, domperidone, quinacrine, ketoconazole,
      verapamil, tacrine, and salmeterol. These findings are discussed in context to
      potential drug interactions that could be observed between these agents and drugs
      for which aldehyde oxidase is involved in metabolism and warrant investigation of
      the possibility of clinical drug interactions mediated by inhibition of this
      enzyme.

PMID- 14681338
TI  - Global burden of disease (GBD) for hepatitis C.
AB  - Hepatitis C virus (HCV) infection is now a global public health issue. However,
      the global burden of disease attributable to HCV infection is unknown. The
      objectives of this WHO informal consultation included the following: (1) defining
      a strategy to estimate the global burden of disease (GBD) associated with HCV
      infection in terms of morbidity and mortality, (2) describing the natural history
      of HCV infection in terms of morbidity and mortality, and (3) identifying areas
      for which more research is needed. The GBD project is an attempt to examine all
      causes of morbidity and mortality using an approach common to all conditions. The
      World Health Organization (WHO) already has estimated the burden of disease
      associated with hepatitis B virus (HBV) infection and is now about to conduct the
      same analysis for HCV infection. A review has been conducted to estimate the
      prevalence of HCV infection by age, gender, and region. These figures can be used
      to estimate incidence, although there are a number of areas of uncertainty.
      Combined with natural history parameters, incidence estimates could be used to
      estimate the future burden due to current infections. However, the present model
      is not validated and requires calibration before it can be used. A consensus was
      reached over the strategies to be used to (1) estimate the current burden due to
      past infections and (2) estimate the future burden due to current infections.
      Provisional expert consensus was reached over natural history parameters and
      cofactors that influence them. However, systematic literature reviews and meta
      analysis are preferable for obtaining estimates to be included in models. Areas
      deserving future research include (1) obtaining a better estimate of HCV
      infection prevalence by age groups, (2) characterizing the various morbidity
      states associated with HCV infection and their disability weights, (3)
      understanding the long-term natural history of HCV infection beyond 20 years
      after infection, and (4) estimating the prevalence (and numbers of) of HCV
      infection among the drug-using population worldwide. A working group was created
      to address unmet needs and to assist the WHO in estimating the GBD associated
      with HCV infection.

PMID- 14681339
TI  - Putting clinical pharmacology in context: the use of popular movies.
AB  - The usefulness of movies to illustrate the psychological and sociological
      conflicts of medical practice is widely recognized. However, the use of popular
      movies to teach less oriented medical sciences, such as pharmacology is not so
      common. In the present review, we report the use of three films (Awakenings,
      Lorenzo's Oil, and Miss Evers' Boys) as a teaching tool to allow students to
      better understand some conflicts which appear in the domain of clinical
      pharmacology. These movies may help to introduce some relevant topics such as the
      difficulties of planning and performing clinical research with new drugs, the
      need of considering bioethical principles when doing research with human beings,
      and the social and psychological aspects of drug therapy. The films may increase
      the motivation of students to understand clinical pharmacology principles and may
      become a driving force for an increased desire to learn.

PMID- 14681340
TI  - Risk-benefit value of inhaled glucocorticoids: a pharmacokinetic/pharmacodynamic
      perspective.
AB  - Inhaled glucocorticoids induce therapeutic and adverse systemic effects via the
      same types of receptors. Analysis of the pharmacokinetic/pharmacodynamic
      parameters of inhaled glucocorticoids generates a risk-benefit value (RBV).
      Targeted efficacy with minimal adverse effects helps to quantify an appropriate
      RBV. High lung deposition/targeting, high receptor binding, longer pulmonary
      retention, and high lipid conjugation are among the pharmacokinetic parameters to
      be considered for improved efficacy of the compound. Low or negligible oral
      bioavailability, small particle size and inactive drug at the oropharynx, high
      plasma protein binding, rapid metabolism, high clearance, and lower systemic
      concentrations are associated with low risks for adverse effects. Inhaled
      glucocorticoid potency is enhanced by solution inhalers, which result in higher
      pulmonary deposition and minimize local adverse effects. These properties, among
      others, determine the efficacy and safety of inhaled glucocorticoids. Currently
      available inhaled glucocorticoids do not provide the complete
      pharmacokinetic/pharmacodynamic parameters to optimize RBV, leaving room for
      improvement in the development of future agents.

PMID- 14681341
TI  - Pharmacokinetics of etoricoxib in patients with renal impairment.
AB  - The effect of renal insufficiency on the pharmacokinetics of etoricoxib, a
      selective inhibitor of cyclooxygenase-2, was examined in 23 patients with varying
      degrees of renal impairment (12 moderate [creatinine clearance between 30 and 50
      mL/min/1.73 m2], 5 severe [creatinine clearance below 30 mL/min/1.73 m2], and 6
      with end-stage renal disease requiring hemodialysis) following administration of
      single 120-mg oral doses of etoricoxib. Even the most severe renal impairment was
      found to have little effect on etoricoxib pharmacokinetics. The low recovery of
      etoricoxib in dialysate (less than 6% of the dose) supports that hemodialysis
      also has little effect on etoricoxib pharmacokinetics, and binding of etoricoxib
      to plasma proteins was generally unaffected by renal disease. Single doses of
      etoricoxib were generally well tolerated by patients with renal impairment. Based
      on pharmacokinetic considerations, dosing adjustments are not necessary for
      patients with any degree of renal impairment. However, because patients with
      advanced renal disease (creatinine clearance below 30 mL/min/1.73 m2) are likely
      to be very sensitive to any further compromise of renal function, and there is no
      long-term clinical experience in these patients, the use of etoricoxib is not
      recommended in patients with advanced renal disease.

PMID- 14681342
TI  - Pharmacokinetics and pharmacodynamics of the ETA-selective endothelin receptor
      antagonist SPP301 in healthy human subjects.
AB  - SPP301 is a competitive antagonist of ET-1 with a high selectivity for the ETA
      receptor. A double-blind, placebo-controlled study was performed to investigate
      the tolerability, pharmacokinetics, and pharmacodynamics of SPP301 after single
      oral doses in male healthy subjects; doses of 5, 20, 50, 100, and 200 mg were
      given to different groups of 4 or 8 subjects each. The effect of food on the
      pharmacokinetics of SPP301 was assessed for the 50-mg dose according to a
      sequential design in the same subjects. At regular intervals, blood pressure and
      pulse rate, plasma levels of ET-1 and of SPP301 and its hydroxymethyl metabolite,
      and urinary excretion of the parent drug and its metabolite were determined.
      SPP301 was generally well tolerated. At doses >20 mg, adverse events that are
      typical for vasodilating agents-namely, headache, nausea and vomiting, dizziness,
      and postural hypotension-were observed. Maximum plasma levels of SPP301 were
      reached within 4.5 hours. Cmax and AUC values increased linearly with doses up to
      100 mg. The apparent terminal half-life was quite constant over the whole dose
      range and ranged from 7.5 to 15.2 hours. Urinary excretion of SPP301 was below
      0.1% of any dose. Cmax and AUC of the metabolite amounted only to about 5% of the
      values for SPP301. Concomitant food intake had no effect on the overall exposure
      but increased average peak plasma concentrations of SPP301 by around 50%. Plasma
      ET-1 increased nearly twofold at the 5-mg SPP301 dose, with no further relevant
      increase at higher doses. In conclusion, SPP301 is an active ET-1 antagonist and
      is well tolerated. The pharmacokinetics of the drug and its metabolite are linear
      up to 100 mg. Food does not affect overall exposure of SPP301 but increases Cmax.
      Urinary excretion of SPP301 is below 0.1% of the dose administered.

PMID- 14681343
TI  - The pharmacokinetics of nebulized nanocrystal budesonide suspension in healthy
      volunteers.
AB  - Nanocrystal budesonide (nanobudesonide) is a suspension for nebulization in
      patients with steroid-responsive pulmonary diseases such as asthma. The
      pharmacokinetics and safety of the product were compared to those of Pulmicort
      Respules. Sixteen healthy volunteers were administered nanobudesonide 0.5 and 1.0
      mg, Pulmicort Respules 0.5 mg, and placebo in a four-way, randomized crossover
      design. All nebulized formulations were well tolerated, with no evidence of
      bronchospasm. Nebulization times were significantly shorter for nanobudesonide
      compared to Pulmicort Respules. Because of a low oral bioavailability, plasma
      concentration of budesonide is a good marker of lung-delivered dose. The
      pharmacokinetics of nanobudesonide 0.5 and 1.0 mg were approximately dose
      proportional with respect to Cmax, AUC(0-t), and AUC(0-infinity). Nanobudesonide
      0.5 mg and Pulmicort Respules 0.5 mg exhibited similar AUCs, suggesting a similar
      extent of pulmonary absorption. A higher Cmax was noted with nanobudesonide 0.5
      mg, and the tmax was significantly different, suggesting a more rapid rate of
      drug delivery of nanobudesonide 0.5 mg than Pulmicort Respules. In conclusion,
      nebulized nanobudesonide 0.5 mg was safe in healthy volunteers, with a similar
      extent of absorption as Pulmicort Respules.

PMID- 14681344
TI  - Pharmacokinetic and pharmacodynamic evaluation of a novel proton pump inhibitor,
      YH1885, in healthy volunteers.
AB  - To evaluate the pharmacokinetic and pharmacodynamic characteristics of YH1885, a
      novel proton pump inhibitor, a single-blind, randomized, placebo-controlled, dose
      rising, parallel-group study was conducted in 46 healthy volunteers. The
      volunteers were randomly allocated to single dose groups of 60 mg, 100 mg, 150
      mg, 200 mg, and 300 mg (6 subjects per dose, including 2 placebos) or to multiple
      dose groups of 150 mg and 300 mg (once-daily dosing for 7 days; 8 subjects per
      dose, including 2 placebos). The multiple-dose study was conducted separately
      after the single-dose study. YH1885 was administered orally after overnight
      fasting. Serial blood samples, urine samples, and pharmacodynamic measurements
      were taken. Drug concentrations in plasma and urine were determined by liquid
      chromatography/mass spectrometry (LC/MS). Pharmacodynamic changes were evaluated
      by ambulatory intragastric pH monitoring and by serial measurements of serum
      gastrin concentrations. Assessments of safety and tolerability also were made.
      Plasma concentrations of YH1885 reached peak levels 1.3 to 2.5 hours after single
      dose administration and then declined monoexponentially with a terminal half-life
      (t(1/2)) of 2.2 to 2.4 hours in dosage groups up to 200 mg in the single-dose
      study. YH1885 showed linear pharmacokinetic characteristics, and little
      accumulation occurred after multiple administrations. The parent drug was not
      detected in urine. Dose-related pharmacological effects were obvious for dose
      groups of 150 mg and higher in the single-dose study. The mean intragastric pH
      and the percentage of time at pH>4 were significantly increased. The onset of
      drug effect was rapid, and maximal effects were observed on the first day of
      administration during multiple dosing. Serum gastrin levels also showed rapid
      increases during dosing but with a weak dose-effect relationship. Neither serious
      nor dose-limiting adverse effects were observed. YH1885 was found to be safe and
      well tolerated and effectively inhibited acid secretion with dose-dependent
      increases in intragastric pH. The acid-suppressing efficacy of YH1885 needs to be
      further evaluated in patients with gastric acid-related diseases.

PMID- 14681345
TI  - Absolute bioavailability and pharmacokinetics of treprostinil sodium administered
      by acute subcutaneous infusion.
AB  - The objective of this study was to evaluate the absolute bioavailability and
      acute pharmacokinetics of treprostinil sodium administered by continuous, short
      term subcutaneous infusion in normal subjects. Fifteen healthy volunteers
      received treprostinil via an intravenous infusion at 15 ng/kg/min over 150
      minutes, followed by a 5- to 7-day washout and a subcutaneous infusion at the
      same rate administered over 150 minutes. Serial plasma samples were collected
      predosing, during dosing, and postdosing, and plasma treprostinil concentration
      levels were measured by a validated liquid chromatography atmospheric pressure
      ionization tandem mass spectrometry (LC/MS/MS) method with a lower limit of
      quantitation (LLOQ) of 25 pg/mL. Acute administration of treprostinil
      administered by subcutaneous infusion at a rate of 15 ng/kg/min for 150 minutes
      achieved a mean Cmax of 1.47 ng/mL. Mean AUC infinity values for intravenous and
      subcutaneous dosing were 3.52 and 3.97 ng.h/mL, respectively, resulting in a mean
      apparent absolute bioavailability of 113% for subcutaneous administration. It was
      possible that the area under of the curve for the intravenous administration was
      underestimated because most of the terminal elimination phase could not be
      documented due to the LLOQ of the assay. The mean apparent elimination half-life
      of treprostinil following subcutaneous administration was 1.38 hours, compared to
      0.87 hours following intravenous administration. It was concluded that
      treprostinil administered by subcutaneous administration is completely absorbed,
      with a slightly longer half-life compared to intravenously administered
      treprostinil.

PMID- 14681346
TI  - Effects of St. John's wort (Hypericum perforatum) on tacrolimus pharmacokinetics
      in healthy volunteers.
AB  - Tacrolimus is an immunosuppressant approved for the prevention of rejection
      following transplantation and is a substrate for CYP3A and P-glycoprotein. A
      pharmacokinetic interaction between St. John's wort (antidepressant herbal
      product and inducer of CYP3A and P-glycoprotein) and tacrolimus was evaluated in
      10 healthy volunteers. The pharmacokinetics of tacrolimus were obtained from
      serial blood samples collected following single oral doses (0.1 mg/kg) prior to
      and during an 18-day concomitant St. John's wort dosing phase (300 mg orally
      three times daily). Coadministration of St. John's wort significantly decreased
      tacrolimus AUC (306.9 microg.h/L +/- 175.8 microg.h/L vs. 198.7 microg.h/L +/-
      139.6 microg.h/L; p=0.004) and increased apparent oral clearance (349.0 mL/h/kg
      +/- 126.0 mL/h/kg vs. 586.4 mL/h/kg +/- 274.9 mL/h/kg; p=0.01) and apparent oral
      volume of distribution at steady state (11.5 L/kg +/- 4.3 L/kg vs. 17.6 L/kg +/-
      9.6 L/kg; p=0.04). St. John's wort appears to induce tacrolimus metabolism, most
      likely through induction of CYP3A and P-glycoprotein.

PMID- 14681347
TI  - Effect of St. John's wort on the pharmacokinetics of theophylline in healthy
      volunteers.
AB  - The objective of this study was to investigate the effect of St. John's wort
      (SJW, Hypericum perforatum) on the pharmacokinetics of theophylline in healthy
      volunteers. Twelve healthy Japanese male volunteers participated in this
      randomized, open-labeled, crossover study. The subjects took an SJW caplet (300
      mg) three times a day for 15 days. On day 14, they received a single oral dose of
      400 mg of theophylline. They took the same dose of theophylline without SJW
      treatment on another occasion. Plasma and urine samples were obtained during a 48
      hour period after theophylline administration. Theophylline concentrations in
      plasma and urine, as well as the major metabolites (13U, 1U, 3X) in urine, were
      measured. SJW caused no significant changes in the pharmacokinetics of
      theophylline in plasma. SJW administration tended to increase the ratio of 1U/the
      total amount excreted in urine. However, no changes in the ratio of unchanged
      theophylline, 13U, and 3X were observed. It is unlikely that the effect of 15
      days of treatment with SJW on CYPs is sufficient to cause a change in plasma
      theophylline concentrations.

PMID- 14681349
TI  - The Molecular Biology Database Collection: 2004 update.
AB  - The Molecular Biology Database Collection is a public resource listing key
      databases of value to the biologist, including those featured in this issue of
      Nucleic Acids Research, and other high-quality databases. All databases included
      in this Collection are freely available to the public. This listing aims to serve
      as a convenient starting point for searching the web for reliable information on
      various aspects of molecular biology, biochemistry and genetics. This year's
      update includes 548 databases, 162 more than the previous one. The databases are
      organized in a hierarchical classification that should simplify finding the right
      database for each given task. Each database in the list comes with a recently
      updated brief description. The database list and the database descriptions can be
      accessed online at the Nucleic Acids Research web site http://nar.
      oupjournals.org/.

PMID- 14681350
TI  - GenBank: update.
AB  - GenBank is a comprehensive database that contains publicly available DNA
      sequences for more than 140 000 named organisms, obtained primarily through
      submissions from individual laboratories and batch submissions from large-scale
      sequencing projects. Most submissions are made using the BankIt (web) or Sequin
      program and accession numbers are assigned by GenBank staff upon receipt. Daily
      data exchange with the EMBL Data Library in the UK and the DNA Data Bank of Japan
      helps ensure worldwide coverage. GenBank is accessible through NCBI's retrieval
      system, Entrez, which integrates data from the major DNA and protein sequence
      databases along with taxonomy, genome mapping, protein structure and domain
      information, and the biomedical journal literature via PubMed. BLAST provides
      sequence similarity searches of GenBank and other sequence databases. Complete
      bimonthly releases and daily updates of the GenBank database are available by
      FTP. To access GenBank and its related retrieval and analysis services, go to the
      NCBI home page at: http://www.ncbi.nlm.nih.gov.

PMID- 14681351
TI  - The EMBL Nucleotide Sequence Database.
AB  - The EMBL Nucleotide Sequence Database (http://www.ebi.ac.uk/embl/), maintained at
      the European Bioinformatics Institute (EBI), incorporates, organizes and
      distributes nucleotide sequences from public sources. The database is a part of
      an international collaboration with DDBJ (Japan) and GenBank (USA). Data are
      exchanged between the collaborating databases on a daily basis to achieve optimal
      synchrony. The web-based tool, Webin, is the preferred system for individual
      submission of nucleotide sequences, including Third Party Annotation (TPA) and
      alignment data. Automatic submission procedures are used for submission of data
      from large-scale genome sequencing centres and from the European Patent Office.
      Database releases are produced quarterly. The latest data collection can be
      accessed via FTP, email and WWW interfaces. The EBI's Sequence Retrieval System
      (SRS) integrates and links the main nucleotide and protein databases as well as
      many other specialist molecular biology databases. For sequence similarity
      searching, a variety of tools (e.g. FASTA and BLAST) are available that allow
      external users to compare their own sequences against the data in the EMBL
      Nucleotide Sequence Database, the complete genomic component subsection of the
      database, the WGS data sets and other databases. All available resources can be
      accessed via the EBI home page at http://www.ebi.ac.uk.

PMID- 14681352
TI  - DDBJ in the stream of various biological data.
AB  - In the past year we at DDBJ (http://www.ddbj.nig. ac.jp) have made a steady
      increase in the number of data submissions with a 50.6% increment in the number
      of bases or 46.5% increment in the number of entries. Among them the genome data
      of man, ascidian and rice hold the top three. Our activity has extended to
      providing a tool that enables sequence retrieval using regular expressions, and
      to launching our SOAP server and web services to facilitate the acquisition of
      proper data and tools from a huge number of biological data resources on websites
      worldwide. We have also opened our public gene expression database, CIBEX.

PMID- 14681353
TI  - Database resources of the National Center for Biotechnology Information: update.
AB  - In addition to maintaining the GenBank(R) nucleic acid sequence database, the
      National Center for Biotechnology Information (NCBI) provides data analysis and
      retrieval resources for the data in GenBank and other biological data made
      available through NCBI's website. NCBI resources include Entrez, PubMed, PubMed
      Central, LocusLink, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink),
      Electronic PCR, OrfFinder, Spidey, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC,
      dbSNP, Cancer Chromosome Aberration Project (CCAP), Entrez Genomes and related
      tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous
      Groups (COGs) database, Retroviral Genotyping Tools, SARS Coronavirus Resource,
      SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man
      (OMIM), the Molecular Modeling Database (MMDB), the Conserved Domain Database
      (CDD) and the Conserved Domain Architecture Retrieval Tool (CDART). Augmenting
      many of the web applications are custom implementations of the BLAST program
      optimized to search specialized data sets. All of the resources can be accessed
      through the NCBI home page at: http://www.ncbi.nlm.nih.gov.

PMID- 14681354
TI  - MIPS: analysis and annotation of proteins from whole genomes.
AB  - The Munich Information Center for Protein Sequences (MIPS-GSF), Neuherberg,
      Germany, provides protein sequence-related information based on whole-genome
      analysis. The main focus of the work is directed toward the systematic
      organization of sequence-related attributes as gathered by a variety of
      algorithms, primary information from experimental data together with information
      compiled from the scientific literature. MIPS maintains automatically generated
      and manually annotated genome-specific databases, develops systematic
      classification schemes for the functional annotation of protein sequences and
      provides tools for the comprehensive analysis of protein sequences. This report
      updates the information on the yeast genome (CYGD), the Neurospora crassa genome
      (MNCDB), the database of complete cDNAs (German Human Genome Project, NGFN), the
      database of mammalian protein-protein interactions (MPPI), the database of FASTA
      homologies (SIMAP), and the interface for the fast retrieval of protein
      associated information (QUIPOS). The Arabidopsis thaliana database, the rice
      database, the plant EST databases (MATDB, MOsDB, SPUTNIK), as well as the
      databases for the comprehensive set of genomes (PEDANT genomes) are described
      elsewhere in the 2003 and 2004 NAR database issues, respectively. All databases
      described, and the detailed descriptions of our projects can be accessed through
      the MIPS web server (http://mips.gsf.de).

PMID- 14681355
TI  - ACLAME: a CLAssification of Mobile genetic Elements.
AB  - The ACLAME database (http://aclame.ulb.ac.be) is a collection and classification
      of prokaryotic mobile genetic elements (MGEs) from various sources, comprising
      all known phage genomes, plasmids and transposons. In addition to providing
      information on the full genomes and genetic entities, it aims to build a
      comprehensive classification of the functional modules of MGEs at the protein,
      gene and higher levels. This first version contains a comprehensive
      classification of 5069 proteins from 119 DNA bacteriophages into over 400
      functional families. This classification was produced automatically using TRIBE
      MCL, a graph-theory-based Markov clustering algorithm that uses sequence measures
      as input, and then manually curated. Manual curation was aided by consulting
      annotations available in public databases retrieved through additional sequence
      similarity searches using Psi-Blast and Hidden Markov Models. The database is
      publicly accessible and open to expert volunteers willing to participate in its
      curation. Its web interface allows browsing as well as querying the
      classification. The main objectives are to collect and organize in a rational way
      the complexity inherent to MGEs, to extend and improve the inadequate annotation
      currently associated with MGEs and to screen known genomes for the validation and
      discovery of new MGEs.

PMID- 14681356
TI  - HERVd: the Human Endogenous RetroViruses Database: update.
AB  - An elaboration of HERVd (http://herv.img.cas.cz) is being carried out in two
      directions. One of them is the integration and better classification of families
      that diverge considerably from typical retroviral genomes. This leads to a more
      precise identification of members with individual families. The second
      improvement is better accessibility of the database and connection with human
      genome annotation.

PMID- 14681357
TI  - IMGT/GeneInfo: enhancing V(D)J recombination database accessibility.
AB  - IMGT/GeneInfo is a user-friendly online information system that provides
      information on data resulting from the complex mechanisms of immunoglobulin (IG)
      and T cell receptor (TR) V(D)J recombinations. For the first time, it is possible
      to visualize all the rearrangement parameters on a single page. IMGT/GeneInfo is
      part of the international ImMunoGeneTics information system (IMGT), a high
      quality integrated knowledge resource specializing in IG, TR, major
      histocompatibility complex (MHC), and related proteins of the immune system of
      human and other vertebrate species. The IMGT/GeneInfo system was developed by the
      TIMC and ICH laboratories (with the collaboration of LIGM), and is the first
      example of an external system being incorporated into IMGT. In this paper, we
      report the first part of this work. IMGT/GeneInfo_TR deals with the human and
      mouse TRA/TRD and TRB loci of the TR. Data handling and visualization are
      complementary to the current data and tools in IMGT, and will subsequently allow
      the modelling of V(D)J gene use, and thus, to predict non-standard recombination
      profiles which may eventually be found in conditions such as leukaemias or
      lymphomas. Access to IMGT/GeneInfo is free and can be found at
      http://imgt.cines.fr/GeneInfo.

PMID- 14681358
TI  - Islander: a database of integrative islands in prokaryotic genomes, the
      associated integrases and their DNA site specificities.
AB  - Prokaryotic chromosomes often contain islands, such as temperate phages or
      pathogenicity islands, delivered by site-specific integrases. Integration usually
      occurs within a tRNA or tmRNA gene, splitting the gene, yet sequences within the
      island restore the disrupted gene. The regenerated RNA gene and the displaced
      fragment of that gene thus mark the endpoints of the island. We applied this
      principle to search for islands in genomic DNA sequences. Our algorithm generates
      a list of tRNA and tmRNA genes, uses each as the query for a BLAST search of the
      starting DNA and removes unlikely hits through a series of filters. A search for
      islands in 106 whole bacterial genomes produced 143 candidates, with the search
      itself providing an estimate of three false candidates among these. Preliminary
      phylogenetic analysis of the associated integrases reduced this set to 89 cases
      of independently evolved site specificity, which showed strong bias for the tmRNA
      gene. The website Islander (http://www.indiana.edu/ approximately islander)
      presents the candidate islands in GenBank-style files and correlates integrase
      phylogeny with site specificity.

PMID- 14681359
TI  - Xpro: database of eukaryotic protein-encoding genes.
AB  - Xpro is a relational database that contains all the eukaryotic protein-encoding
      DNA sequences contained in GenBank with associated data required for the analysis
      of eukaryotic gene architecture. In addition to the information found in the
      GenBank records, which includes properties such as sequence, position, length and
      description about introns, exons and protein-coding regions, Xpro provides
      annotations on the splice sites and intron phases. Furthermore, Xpro validates
      intron positions using alignment information between the record's sequence and
      EST sequences found in dbEST. In the process of validation, alternative splicing
      information is also obtained and can be found in the database. The intron
      containing genes in the Xpro are also classified as experimental or predicted
      based on the intron position validation and specific keywords in the GenBank
      records that are present in predicted genes. An Entrez-like query system, which
      is familiar to most biologists, is provided for accessing the information present
      in the database system. A non-redundant set of Xpro database contents is also
      obtained by cross-referencing to the Swiss-Prot/TrEMBL and Pfam databases. The
      database currently contains information for 493,983 genes--351,918 intron-
      containing genes and 142,065 intron-less genes. Xpro is updated for each new
      GenBank release and is freely available via the internet at http://origin.bic.
      nus.edu.sg/xpro.

PMID- 14681360
TI  - ASD: the Alternative Splicing Database.
AB  - Alternative splicing is widespread in mammalian gene expression, and variant
      splice patterns are often specific to different stages of development, particular
      tissues or a disease state. There is a need to systematically collect data on
      alternatively spliced exons, introns and splice isoforms, and to annotate this
      data. The Alternative Splicing Database consortium has been addressing this need,
      and is committed to maintaining and developing a value-added database of
      alternative splice events, and of experimentally verified regulatory mechanisms
      that mediate splice variants. In this paper we present two of the products from
      this project: namely, a database of computationally delineated alternative splice
      events as seen in alignments of EST/cDNA sequences with genome sequences, and a
      database of alternatively spliced exons collected from literature. The reported
      splice events are from nine different organisms and are annotated for various
      biological features including expression states and cross-species conservation.
      The data are presented on our ASD web pages (http://www.ebi.ac.uk/asd).

PMID- 14681361
TI  - EASED: Extended Alternatively Spliced EST Database.
AB  - We established a database of alternative splice forms (ASforms) for nine
      eukaryotic organisms. ASforms are defined by comparing high-scoring ESTs with
      mRNA sequences using BLAST, taking known exon-intron information (from the
      Ensembl database). Filtering programs compare the ends of each aligned sequence
      pair for deletions or insertions in the EST sequence, which indicate the
      existence of alternative splice forms with respect to the exon-intron boundaries.
      Moreover, we defined the alternative splice profile of each human sequence. It
      indicates the number of alternatively spliced ESTs (NAE), the number of
      constitutively spliced ESTs (NCE) as well as the number of alternative splice
      sites (NSS) per mRNA. NAE and NCE correspond to the EST coverage and can be used
      as a quality indicator for the predicted alternative splice variants. The NSS
      value specifies the splice propensity of a gene. Additionally, the tissue type
      information of all ESTs was included. This allows (i) restriction of the search
      to certain tissues and (ii) calculation of the tissue-NAEs, tissue-NCEs and
      tissue-NSS. These scores are suitable for the estimation of tissue specificity of
      certain ASforms. Furthermore, the developmental stage and disease information of
      the ESTs is available. EASED is accessible at http://eased.bioinf.mdc-berlin.de/.

PMID- 14681362
TI  - DBTBS: database of transcriptional regulation in Bacillus subtilis and its
      contribution to comparative genomics.
AB  - DBTBS (http://dbtbs.hgc.jp) was originally released in 1999 as a reference
      database of published transcriptional regulation events in Bacillus subtilis, one
      of the best studied bacteria. It is essentially a compilation of transcription
      factors with their regulated genes as well as their recognition sequences, which
      were experimentally characterized and reported in the literature. Here we report
      its major update, which contains information on 114 transcription factors,
      including sigma factors, and 633 promoters of 525 genes. The number of references
      cited in the database has increased from 291 to 378. It also supports a function
      to find putative transcription factor binding sites within input sequences by
      using our collection of weight matrices and consensus patterns. Furthermore,
      though preliminarily, DBTBS now aims to contribute to comparative genomics by
      showing the presence or absence of potentially orthologous transcription factors
      and their corresponding cis-elements on the promoters of their potentially
      orthologously regulated genes in 50 eubacterial genomes.

PMID- 14681364
TI  - The Eukaryotic Promoter Database EPD: the impact of in silico primer extension.
AB  - The Eukaryotic Promoter Database (EPD) is an annotated non-redundant collection
      of eukaryotic POL II promoters, experimentally defined by a transcription start
      site (TSS). There may be multiple promoter entries for a single gene. The
      underlying experimental evidence comes from journal articles and, starting from
      release 73, from 5' ESTs of full-length cDNA clones used for so-called in silico
      primer extension. Access to promoter sequences is provided by pointers to TSS
      positions in nucleotide sequence entries. The annotation part of an EPD entry
      includes a description of the type and source of the initiation site mapping
      data, links to other biological databases and bibliographic references. EPD is
      structured in a way that facilitates dynamic extraction of biologically
      meaningful promoter subsets for comparative sequence analysis. Web-based
      interfaces have been developed that enable the user to view EPD entries in
      different formats, to select and extract promoter sequences according to a
      variety of criteria and to navigate to related databases exploiting different
      cross-references. Tools for analysing sequence motifs around TSSs defined in EPD
      are provided by the signal search analysis server. EPD can be accessed at
      http://www.epd. isb-sib.ch.

PMID- 14681365
TI  - HemoPDB: Hematopoiesis Promoter Database, an information resource of
      transcriptional regulation in blood cell development.
AB  - Hematopoiesis describes the process of the normal formation and development of
      blood cells, involving both proliferation and differentiation from stem cells.
      Abnormalities in this developmental program yield blood cell diseases, such as
      leukemia. Although, in recent years, extensive molecular research in normal
      hematopoietic development has characterized transcription factors and their
      binding sites in the target gene promoters, the information generated is highly
      fragmented. In order to integrate this important regulatory information with the
      corresponding genomic sequences, we have developed a new database called
      Hematopoiesis Promoter Database (HemoPDB). HemoPDB is a comprehensive resource
      focused on transcriptional regulation during hematopoietic development and
      associated aberrances that result in malignancy. HemoPDB (version 1.0) contains
      246 promoter sequences and 604 experimentally known cis-regulatory elements of
      187 different transcription factors, with links to published references.
      Orthologous promoters from different species are linked with each other and
      displayed in the same database record, accompanied by a visual image of the
      promoters and corresponding annotations of cis-regulatory elements. HemoPDB may
      be searched for the promoter of a specific gene, transcription factors and target
      genes, and genes that are expressed in a certain cell type or lineage, through a
      user-friendly web interface at http://bioinformatics.med.ohio-state.edu/HemoPDB.
      Links to the documentation and other technical details are provided on this
      website.

PMID- 14681366
TI  - JASPAR: an open-access database for eukaryotic transcription factor binding
      profiles.
AB  - The analysis of regulatory regions in genome sequences is strongly based on the
      detection of potential transcription factor binding sites. The preferred models
      for representation of transcription factor binding specificity have been termed
      position-specific scoring matrices. JASPAR is an open-access database of
      annotated, high-quality, matrix-based transcription factor binding site profiles
      for multicellular eukaryotes. The profiles were derived exclusively from sets of
      nucleotide sequences experimentally demonstrated to bind transcription factors.
      The database is complemented by a web interface for browsing, searching and
      subset selection, an online sequence analysis utility and a suite of programming
      tools for genome-wide and comparative genomic analysis of regulatory regions.
      JASPAR is available at http://jaspar. cgb.ki.se.

PMID- 14681363
TI  - DBTSS, DataBase of Transcriptional Start Sites: progress report 2004.
AB  - DBTSS (http://dbtss.hgc.jp) was originally constructed based on a collection of
      experimentally determined TSSs of human genes. Since its first release in 2002,
      it has been updated several times. First, the amount of stored data has increased
      significantly: e.g. the number of clones that match both the RefSeq mRNA set and
      the genome sequence has increased from 111,382 to 190,964, now covering 1,234
      genes. Second, the positions of SNPs in dbSNP were displayed on the upstream
      regions of contained human genes. Third, DBTSS now covers other species such as
      mouse and the human malaria parasite. It will become a central database
      containing data for many more species with oligo-capping and related methods.
      Lastly, the database now serves for comparative promoter analyses: in the current
      version, comparative views of potentially orthologous promoters from human and
      mouse are presented with an additional function of searching potential
      transcription-factor binding sites, which are either conserved or diverged
      between species.

PMID- 14681367
TI  - Aptamer database.
AB  - The aptamer database is designed to contain comprehensive sequence information on
      aptamers and unnatural ribozymes that have been generated by in vitro selection
      methods. Such data are not normally collected in 'natural' sequence databases,
      such as GenBank. Besides serving as a storehouse of sequences that may have
      diagnostic or therapeutic utility, the database serves as a valuable resource for
      theoretical biologists who describe and explore fitness landscapes. The database
      is updated monthly and is publicly available at http://aptamer. icmb.utexas.edu/.

PMID- 14681368
TI  - The European ribosomal RNA database.
AB  - The European ribosomal RNA database aims to compile all complete or nearly
      complete ribosomal RNA sequences from both the small (SSU) and large (LSU)
      ribosomal subunits. All sequences are available in aligned format. Sequence
      alignment is based on the secondary structure of the molecules, as determined by
      comparative sequence analysis. Additional information about the sequences, such
      as taxonomic classification of the organism from which they have been obtained,
      and literature references are also provided. In order to identify the closest
      relatives to newly determined sequences, BLAST searches can be performed, after
      which the best matching sequences are aligned and a phylogenetic tree is
      inferred. As of 2003, the European ribosomal RNA database is maintained at Ghent
      University (Belgium). The database can be consulted at
      http://www.psb.ugent.be/rRNA/.

PMID- 14681369
TI  - The tmRNA website: reductive evolution of tmRNA in plastids and other
      endosymbionts.
AB  - tmRNA combines tRNA- and mRNA-like properties and ameliorates problems arising
      from stalled ribosomes. Research on the mechanism, structure and biology of tmRNA
      is served by the tmRNA website (http://www.indiana.edu/~ tmrna), a collection of
      sequences, alignments, secondary structures and other information. Because many
      of these sequences are not in GenBank, a BLAST server has been added; another new
      feature is an abbreviated alignment for the tRNA-like domain only. Many tmRNA
      sequences from plastids have been added, five found in public sequence data and
      another 10 generated by direct sequencing; detection in early-branching members
      of the green plastid lineage brings coverage to all three primary plastid
      lineages. The new sequences include the shortest known tmRNA sequence. While
      bacterial tmRNAs usually have a lone pseudoknot upstream of the mRNA segment and
      a string of three or four pseudoknots downstream, plastid tmRNAs collectively
      show loss of pseudoknots at both postions. The pseudoknot-string region is also
      too short to contain the usual pseudoknot number in another new entry, the tmRNA
      sequence from a bacterial endosymbiont of insect cells, Tremblaya princeps.
      Pseudoknots may optimize tmRNA function in free-living bacteria, yet become
      dispensible when the endosymbiotic lifestyle relaxes selective pressure for fast
      growth.

PMID- 14681370
TI  - The microRNA Registry.
AB  - The miRNA Registry provides a service for the assignment of miRNA gene names
      prior to publication. A comprehensive and searchable database of published miRNA
      sequences is accessible via a web interface
      (http://www.sanger.ac.uk/Software/Rfam/mirna/), and all sequence and annotation
      data are freely available for download. Release 2.0 of the database contains 506
      miRNA entries from six organisms.

PMID- 14681371
TI  - PIRSF: family classification system at the Protein Information Resource.
AB  - The Protein Information Resource (PIR) is an integrated public resource of
      protein informatics. To facilitate the sensible propagation and standardization
      of protein annotation and the systematic detection of annotation errors, PIR has
      extended its superfamily concept and developed the SuperFamily (PIRSF)
      classification system. Based on the evolutionary relationships of whole proteins,
      this classification system allows annotation of both specific biological and
      generic biochemical functions. The system adopts a network structure for protein
      classification from superfamily to subfamily levels. Protein family members are
      homologous (sharing common ancestry) and homeomorphic (sharing full-length
      sequence similarity with common domain architecture). The PIRSF database consists
      of two data sets, preliminary clusters and curated families. The curated families
      include family name, protein membership, parent-child relationship, domain
      architecture, and optional description and bibliography. PIRSF is accessible from
      the website at http://pir.georgetown.edu/pirsf/ for report retrieval and sequence
      classification. The report presents family annotation, membership statistics,
      cross-references to other databases, graphical display of domain architecture,
      and links to multiple sequence alignments and phylogenetic trees for curated
      families. PIRSF can be utilized to analyze phylogenetic profiles, to reveal
      functional convergence and divergence, and to identify interesting relationships
      between homeomorphic families, domains and structural classes.

PMID- 14681372
TI  - UniProt: the Universal Protein knowledgebase.
AB  - To provide the scientific community with a single, centralized, authoritative
      resource for protein sequences and functional information, the Swiss-Prot, TrEMBL
      and PIR protein database activities have united to form the Universal Protein
      Knowledgebase (UniProt) consortium. Our mission is to provide a comprehensive,
      fully classified, richly and accurately annotated protein sequence knowledgebase,
      with extensive cross-references and query interfaces. The central database will
      have two sections, corresponding to the familiar Swiss-Prot (fully manually
      curated entries) and TrEMBL (enriched with automated classification, annotation
      and extensive cross-references). For convenient sequence searches, UniProt also
      provides several non-redundant sequence databases. The UniProt NREF (UniRef)
      databases provide representative subsets of the knowledgebase suitable for
      efficient searching. The comprehensive UniProt Archive (UniParc) is updated daily
      from many public source databases. The UniProt databases can be accessed online
      (http://www.uniprot.org) or downloaded in several formats
      (ftp://ftp.uniprot.org/pub). The scientific community is encouraged to submit
      data for inclusion in UniProt.

PMID- 14681373
TI  - ProTherm, version 4.0: thermodynamic database for proteins and mutants.
AB  - Release 4.0 of ProTherm, thermodynamic database for proteins and mutants,
      contains approximately 14,500 numerical data (approximately 450% of the first
      version) of several thermodynamic parameters along with experimental methods and
      conditions, and structural, functional and literature information. The sequence
      and structural information of proteins is connected with thermodynamic data
      through links between entries in Protein Data Bank, Protein Information Resource
      and SWISS-PROT and the data in ProTherm. We have separated the Gibbs free energy
      change obtained at extrapolated temperature from the data on denaturation
      temperature measured by the thermal denaturation method. We have added the
      statistics of amino acid replacements and links to homologous structures to each
      protein. Further, we have improved the search and display options to enhance
      search capability through the web interface. ProTherm is freely available at
      http://gibk26. bse.kyutech.ac.jp/jouhou/Protherm/protherm.html.

PMID- 14681374
TI  - DBSubLoc: database of protein subcellular localization.
AB  - We have built a protein subcellular localization annotation database, the
      DBSubLoc database, which is available at http://www.bioinfo.tsinghua.
      edu.cn/dbsubloc.html. Annotations were taken from primary protein databases,
      model organism genome projects and literature texts, and then were analyzed to
      dig out the subcellular localization features of the proteins. The proteins are
      also classified into different categories. Based on sequence alignment, non
      redundant subsets of the database have been built, which may provide useful
      information for subcellular localization prediction. The database now contains
      >60,000 protein sequences including approximately 30,000 protein sequences in the
      non-redundant data sets. Online download, search and Blast tools are also
      available.

PMID- 14681375
TI  - THGS: a web-based database of Transmembrane Helices in Genome Sequences.
AB  - Transmembrane Helices in Genome Sequences (THGS) is an interactive web-based
      database, developed to search the transmembrane helices in the user-interested
      gene sequences available in the Genome Database (GDB). The proposed database has
      provision to search sequence motifs in transmembrane and globular proteins. In
      addition, the motif can be searched in the other sequence databases (Swiss-Prot
      and PIR) or in the macromolecular structure database, Protein Data Bank (PDB).
      Further, the 3D structure of the corresponding queried motif, if it is available
      in the solved protein structures deposited in the Protein Data Bank, can also be
      visualized using the widely used graphics package RASMOL. All the sequence
      databases used in the present work are updated frequently and hence the results
      produced are up to date. The database THGS is freely available via the world wide
      web and can be accessed at http:// pranag.physics.iisc.ernet.in/thgs/ or
      http://144.16. 71.10/thgs/.

PMID- 14681376
TI  - The Catalytic Site Atlas: a resource of catalytic sites and residues identified
      in enzymes using structural data.
AB  - The Catalytic Site Atlas (CSA) provides catalytic residue annotation for enzymes
      in the Protein Data Bank. It is available online at http://www.ebi.ac.uk/thornton
      srv/databases/CSA. The database consists of two types of annotated site: an
      original hand-annotated set containing information extracted from the primary
      literature, using defined criteria to assign catalytic residues, and an
      additional homologous set, containing annotations inferred by PSI-BLAST and
      sequence alignment to one of the original set. The CSA can be queried via Swiss
      Prot identifier and EC number, as well as by PDB code. CSA Version 1.0 contains
      177 original hand- annotated entries and 2608 homologous entries, and covers
      approximately 30% of all EC numbers found in PDB. The CSA will be updated on a
      monthly basis to include homologous sites found in new PDBs, and new hand
      annotated enzymes as and when their annotation is completed.

PMID- 14681377
TI  - Recent improvements to the PROSITE database.
AB  - The PROSITE database consists of a large collection of biologically meaningful
      signatures that are described as patterns or profiles. Each signature is linked
      to documentation that provides useful biological information on the protein
      family, domain or functional site identified by the signature. The PROSITE web
      page has been redesigned and several tools have been implemented to help the user
      discover new conserved regions in their own proteins and to visualize domain
      arrangements. We also introduced the facility to search PDB with a PROSITE entry
      or a user's pattern and visualize matched positions on 3D structures. The latest
      version of PROSITE (release 18.17 of November 30, 2003) contains 1676 entries.
      The database is accessible at http://www.expasy.org/prosite/.

PMID- 14681378
TI  - The Pfam protein families database.
AB  - Pfam is a large collection of protein families and domains. Over the past 2 years
      the number of families in Pfam has doubled and now stands at 6190 (version 10.0).
      Methodology improvements for searching the Pfam collection locally as well as via
      the web are described. Other recent innovations include modelling of
      discontinuous domains allowing Pfam domain definitions to be closer to those
      found in structure databases. Pfam is available on the web in the UK
      (http://www.sanger.ac.uk/Software/Pfam/), the USA (http://pfam.wustl.edu/),
      France (http://pfam.jouy.inra.fr/) and Sweden (http://Pfam.cgb.ki.se/).

PMID- 14681379
TI  - SMART 4.0: towards genomic data integration.
AB  - SMART (Simple Modular Architecture Research Tool) is a web tool
      (http://smart.embl.de/) for the identification and annotation of protein domains,
      and provides a platform for the comparative study of complex domain architectures
      in genes and proteins. The January 2004 release of SMART contains 685 protein
      domains. New developments in SMART are centred on the integration of data from
      completed metazoan genomes. SMART now uses predicted proteins from complete
      genomes in its source sequence databases, and integrates these with predictions
      of orthology. New visualization tools have been developed to allow analysis of
      gene intron-exon structure within the context of protein domain structure, and to
      align these displays to provide schematic comparisons of orthologous genes, or
      multiple transcripts from the same gene. Other improvements include the ability
      to query SMART by Gene Ontology terms, improved structure database searching and
      batch retrieval of multiple entries.

PMID- 14681380
TI  - ESTHER, the database of the alpha/beta-hydrolase fold superfamily of proteins.
AB  - The alpha/beta-hydrolase fold is characterized by a beta-sheet core of five to
      eight strands connected by alpha-helices to form a alpha/beta/alpha sandwich. In
      most of the family members the beta-strands are parallels, but some show an
      inversion in the order of the first strands, resulting in antiparallel
      orientation. The members of the superfamily diverged from a common ancestor into
      a number of hydrolytic enzymes with a wide range of substrate specificities,
      together with other proteins with no recognized catalytic activity. In the
      enzymes the catalytic triad residues are presented on loops, of which one, the
      nucleophile elbow, is the most conserved feature of the fold. Of the other
      proteins, which all lack from one to all of the catalytic residues, some may
      simply be 'inactive' enzymes while others are known to be involved in surface
      recognition functions. The ESTHER database (http://bioweb.ensam.inra.fr/esther)
      gathers and annotates all the published information related to gene and protein
      sequences of this superfamily, as well as biochemical, pharmacological and
      structural data, and connects them so as to provide the bases for studying
      structure-function relationships within the family. The most recent developments
      of the database, which include a section on human diseases related to members of
      the family, are described.

PMID- 14681381
TI  - EyeSite: a semi-automated database of protein families in the eye.
AB  - The EyeSite is a web-based database of protein families for proteins that
      function in the eye and their homologous sequences. The resource clusters
      proteins at different levels of homology in order to facilitate functional
      annotation of sequences and modelling of proteins from structural homologues. Eye
      proteins are organized into the tissue types in which they function and are
      clustered into homologous families using a novel protocol employing the TribeMCL
      algorithm. Homologous families are further subdivided into sequence clusters for
      which multiple sequence alignments are generated. Structural annotations from the
      CATH domain database are provided for nearly 90% of the sequences, and protein
      family annotations from the Pfam database for approximately 86%. Homology models
      have also been generated where appropriate. The EyeSite is stored in a relational
      database and is extensively linked to other online bioinformatics resources to
      help relate allelic variants, annotations and clinical details to the derived
      data in the database. The EyeSite is available for online search, sequence
      information and model retrieval at http://eyesite.cryst.bbk.ac.uk/.

PMID- 14681382
TI  - KinG: a database of protein kinases in genomes.
AB  - The KinG database is a comprehensive collection of serine/threonine/tyrosine
      specific kinases and their homologues identified in various completed genomes
      using sequence and profile search methods. The database hosted at http://hodgkin.
      mbu.iisc.ernet.in/ approximately king provides the amino acid sequences,
      functional domain assignments and classification of gene products containing
      protein kinase domains. A search tool enabling the retrieval of protein kinases
      with specified subfamily and domain combinations is one of the key features of
      the resource. Identification of a kinase catalytic domain in the user's query
      sequence is possible using another search tool. The occurrence and location of
      critical catalytic residues if the query has a catalytic kinase domain,
      recognition of non-kinase domains in the sequence and subfamily classification of
      the kinase in the query will help in deciphering the biological role of the
      kinase. This online compilation can also be used to compare the protein kinases
      of a given subfamily and domain combinations across various genomes. Another
      exclusive feature of the database is the collection of the Ser/Thr/Tyr protein
      kinases and similar sequences encoded in the genomes of archaea and bacteria.

PMID- 14681383
TI  - The KNOTTIN website and database: a new information system dedicated to the
      knottin scaffold.
AB  - The KNOTTIN website and database organize information about knottins or inhibitor
      cystine knots, small disulfide-rich proteins with a knotted topology. Thanks to
      their small size and high stability, knottins provide appealing scaffolds for
      protein engineering and drug design. Static pages present the main historical and
      recent results about knottin discoveries, sequences, structures, folding,
      functions, applications and bibliography. Database searches provide dynamically
      generated tabular reports or sequence alignments for knottin three-dimensional
      structures or sequences. BLAST/HMM searches are also available. A simple
      nomenclature, based on loop lengths between cysteines, is proposed and is
      complemented by a uniform numbering scheme. This standardization is applied to
      all knottin structures in the database, facilitating comparisons. Renumbered and
      structurally fitted knottin PDB files are available for download. The
      standardized numbering is used for automatic drawing of two-dimensional Colliers
      de Perles. The KNOTTIN website and database are available at
      http://knottin.cbs.cnrs.fr and http://knottin.com.

PMID- 14681384
TI  - MEROPS: the peptidase database.
AB  - Peptidases (proteolytic enzymes) are of great relevance to biology, medicine and
      biotechnology. This practical importance creates a need for an integrated source
      of information about them, and also about their natural inhibitors. The MEROPS
      database (http://merops.sanger.ac.uk) aims to fill this need. The organizational
      principle of the database is a hierarchical classification in which homologous
      sets of the proteins of interest are grouped in families and the homologous
      families are grouped in clans. Each peptidase, family and clan has a unique
      identifier. The database has recently been expanded to include the protein
      inhibitors of peptidases, and these are classified in much the same way as the
      peptidases. Forms of information recently added include new links to other
      databases, summary alignments for peptidase clans, displays to show the
      distribution of peptidases and inhibitors among organisms, substrate cleavage
      sites and indexes for expressed sequence tag libraries containing peptidases. A
      new way of making hyperlinks to the database has been devised and a BlastP search
      of our library of peptidase and inhibitor sequences has been added.

PMID- 14681385
TI  - Update of NUREBASE: nuclear hormone receptor functional genomics.
AB  - Nuclear hormone receptors are an abundant class of ligand-activated
      transcriptional regulators, found in varying numbers in all animals. Based on our
      experience of managing the official nomenclature of nuclear receptors, we have
      developed NUREBASE, a database containing protein and DNA sequences, reviewed
      protein alignments and phylogenies, taxonomy and annotations for all nuclear
      receptors. New developments in NUREBASE include explicit declaration of
      alternative transcripts of each gene, and expression data for human and mouse
      nuclear receptors. The core of NUREBASE is reviewed, and it is completed by
      NUREBASE_DAILY, automatically updated every 24 h. All information on accessing
      and installing NUREBASE may be found at http://www. ens
      lyon.fr/LBMC/laudet/nurebase/nurebase.html.

PMID- 14681386
TI  - RPG: the Ribosomal Protein Gene database.
AB  - RPG (http://ribosome.miyazaki-med.ac.jp/) is a new database that provides
      detailed information about ribosomal protein (RP) genes. It contains data from
      humans and other organisms, including Drosophila melanogaster, Caenorhabditis
      elegans, Saccharo myces cerevisiae, Methanococcus jannaschii and Escherichia
      coli. Users can search the database by gene name and organism. Each record
      includes sequences (genomic, cDNA and amino acid sequences), intron/exon
      structures, genomic locations and information about orthologs. In addition, users
      can view and compare the gene structures of the above organisms and make multiple
      amino acid sequence alignments. RPG also provides information on small nucleolar
      RNAs (snoRNAs) that are encoded in the introns of RP genes.

PMID- 14681387
TI  - TrSDB: a proteome database of transcription factors.
AB  - TrSDB-TranScout Database-(http://ibb.uab.es/trsdb) is a proteome database of
      eukaryotic transcription factors based upon predicted motifs by TranScout and
      data sources such as InterPro and Gene Ontology Annotation. Nine eukaryotic
      proteomes are included in the current version. Extensive and diverse information
      for each database entry, different analyses considering TranScout classification
      and similarity relationships are offered for research on transcription factors or
      gene expression.

PMID- 14681388
TI  - AANT: the Amino Acid-Nucleotide Interaction Database.
AB  - We have created an Amino Acid-Nucleotide Interaction Database (AANT;
      http://aant.icmb.utexas. edu/) that categorizes all amino acid-nucleotide
      interactions from experimentally determined protein-nucleic acid structures, and
      provides users with a graphic interface for visualizing these interactions in
      aggregate. AANT accomplishes this by extracting individual amino acid-nucleotide
      interactions from structures in the Protein Data Bank, combining and
      superimposing these interactions into multiple structure files (e.g. 20 amino
      acids x 5 nucleotides) and grouping structurally similar interactions into more
      readily identifiable clusters. Using the Chime web browser plug-in, users can
      view 3D representations of the superimpositions and clusters. The unique
      collection and representation of data on amino acid-nucleotide interactions
      facilitates understanding the specificity of protein-nucleic acid interactions at
      a more fundamental level, and allows comparison of otherwise extremely disparate
      sets of structures. Moreover, by modularly representing the fundamental
      interactions that govern binding specificity it may prove possible to better
      engineer nucleic acid binding proteins.

PMID- 14681389
TI  - SCOR: Structural Classification of RNA, version 2.0.
AB  - SCOR, the Structural Classification of RNA (http://scor.lbl.gov), is a database
      designed to provide a comprehensive perspective and understanding of RNA motif
      three-dimensional structure, function, tertiary interactions and their
      relationships. SCOR 2.0 represents a major expansion and introduces a new
      classification organization. The new version represents the classification as a
      Directed Acyclic Graph (DAG), which allows a classification node to have multiple
      parents, in contrast to the strictly hierarchical classification used in SCOR
      1.2. SCOR 2.0 supports three types of query terms in the updated search engine:
      PDB or NDB identifier, nucleotide sequence and keyword. We also provide parseable
      XML files for all information. This new release contains 511 RNA entries from the
      PDB as of 15 May 2003. A total of 5880 secondary structural elements are
      classified: 2104 hairpin loops and 3776 internal loops. RNA motifs reported in
      the literature, such as 'Kink turn' and 'GNRA loops', are now incorporated into
      the structural classification along with definitions and descriptions.

PMID- 14681390
TI  - ArchDB: automated protein loop classification as a tool for structural genomics.
AB  - The annotation of protein function has become a crucial problem with the advent
      of sequence and structural genomics initiatives. A large body of evidence
      suggests that protein structural information is frequently encoded in local
      sequences, and that folds are mainly made up of a number of simple local units of
      super-secondary structural motifs, consisting of a few secondary structures and
      their connecting loops. Moreover, protein loops play an important role in protein
      function. Here we present ArchDB, a classification database of structural motifs,
      consisting of one loop plus its bracing secondary structures. ArchDB currently
      contains 12,665 super-secondary elements classified into 1496 motif subclasses.
      The database provides an easy way to retrieve functional information from protein
      structures sharing a common motif, to search motifs found in a given SCOP family,
      superfamily or fold, or to search by keywords on proteins with classified loops.
      The ArchDB database of loops is located at http://sbi.imim.es/archdb.

PMID- 14681391
TI  - The ASTRAL Compendium in 2004.
AB  - The ASTRAL Compendium provides several databases and tools to aid in the analysis
      of protein structures, particularly through the use of their sequences. Partially
      derived from the SCOP database of protein structure domains, it includes
      sequences for each domain and other resources useful for studying these sequences
      and domain structures. The current release of ASTRAL contains 54,745 domains,
      more than three times as many as the initial release 4 years ago. ASTRAL has
      undergone major transformations in the past 2 years. In addition to several
      complete updates each year, ASTRAL is now updated on a weekly basis with
      preliminary classifications of domains from newly released PDB structures. These
      classifications are available as a stand-alone database, as well as integrated
      into other ASTRAL databases such as representative subsets. To enhance the
      utility of ASTRAL to structural biologists, all SCOP domains are now made
      available as PDB-style coordinate files as well as sequences. In addition to
      sequences and representative subsets based on SCOP domains, sequences and subsets
      based on PDB chains are newly included in ASTRAL. Several search tools have been
      added to ASTRAL to facilitate retrieval of data by individual users and automated
      methods. ASTRAL may be accessed at http://astral.stanford. edu/.

PMID- 14681392
TI  - DomIns: a web resource for domain insertions in known protein structures.
AB  - Proteins can be formed by single or multiple domains. The process of
      recombination at the molecular level has generated a wide variety of multi-domain
      proteins with specific domain organization to cater to the functional
      requirements of an organism. The functional and structural costs of inserting a
      domain into another means that multi-domain proteins are usually formed by
      covalently linking the N-terminus of one domain to the C-terminus of the
      preceding domain. While this is true in a large proportion of multi-domain
      proteins, we find a significant fraction of proteins that are the result of
      domain insertion. The inserted domain breaks the sequence contiguity of the
      domain into which it is inserted leading to a novel domain organization. This web
      resource aims to document domain insertions in known protein structures that are
      classified in the SCOP database. The web server can be accessed from
      http://stash.mrc-lmb.cam. ac.uk/DomIns/.

PMID- 14681393
TI  - The Genomic Threading Database: a comprehensive resource for structural
      annotations of the genomes from key organisms.
AB  - Currently, the Genomic Threading Database (GTD) contains structural assignments
      for the proteins encoded within the genomes of nine eukaryotes and 101
      prokaryotes. Structural annotations are carried out using a modified version of
      GenTHREADER, a reliable fold recognition method. The Gen THREADER annotation jobs
      are distributed across multiple clusters of processors using grid technology and
      the predictions are deposited in a relational database accessible via a web
      interface at http://bioinf.cs.ucl.ac.uk/GTD. Using this system, up to 84% of
      proteins encoded within a genome can be confidently assigned to known folds with
      72% of the residues aligned. On average in the GTD, 64% of proteins encoded
      within a genome are confidently assigned to known folds and 58% of the residues
      are aligned to structures.

PMID- 14681394
TI  - DSDBASE: a consortium of native and modelled disulphide bonds in proteins.
AB  - DSDBASE is a database of disulphide bonds in proteins, which provides information
      on native disulphides and those that are stereochemically possible between pairs
      of residues for all known protein structural entries. The modelling of
      disulphides has been performed, using MODIP, by the identification of residue
      pairs that can strainlessly accommodate a covalent cross-link. We also assess the
      stereochemical quality of the covalent cross-link and grade them appropriately.
      One of the potential uses of the database is to design site-directed mutants in
      order to enhance the thermal stability of a protein. The proposed sites of
      mutations can be viewed specifically with respect to active sites of enzymes and
      across physiological dimers. The occurrence of native and modelled disulphides
      increases the dimensions of the database enormously. This database can also be
      employed for proposing three-dimensional models of disulphide-rich short
      polypeptides. The database can be accessed from http://www.ncbs.res.in/
      approximately faculty/mini/dsdbase/dsdbase.html. Supplementary information can be
      accessed from http://www.ncbs.res.in/ approximately
      faculty/mini/dsdbase/nar/suppl.htm.

PMID- 14681395
TI  - HOMSTRAD: recent developments of the Homologous Protein Structure Alignment
      Database.
AB  - HOMSTRAD (http://www-cryst.bioc.cam.ac.uk/ homstrad/) is a collection of protein
      families, clustered on the basis of sequence and structural similarity. The
      database is unique in that the protein family sequence alignments have been
      specially annotated using the program, JOY, to highlight a wide range of
      structural features. Such data are useful for identifying key structurally
      conserved residues within the families. Superpositions of the structures within
      each family are also available and a sensitive structure-aided search engine,
      FUGUE, can be used to search the database for matches to a query protein
      sequence. Historically, HOMSTRAD families were generated using several key pieces
      of software, including COMPARER and MNYFIT, and held in a number of flat files
      and indexes. A new relational database version of HOMSTRAD, HOMSTRAD BETA
      (http://www-cryst.bioc.cam. ac.uk/homstradbeta/) is being developed using MySQL.
      This relational data structure provides more flexibility for future developments,
      reduces update times and makes data more easily accessible. Consequently it has
      been possible to add a number of new web features including a custom alignment
      facility. Altogether, this makes HOMSTRAD and its new BETA version, an excellent
      resource both for comparative modelling and for identifying distant
      sequence/structure similarities between proteins.

PMID- 14681396
TI  - IMGT/3Dstructure-DB and IMGT/StructuralQuery, a database and a tool for
      immunoglobulin, T cell receptor and MHC structural data.
AB  - IMGT/3Dstructure-DB and IMGT/Structural-Query are a novel 3D structure database
      and a new tool for immunological proteins. They are part of IMGT, the
      international ImMunoGenetics information system, a high-quality integrated
      knowledge resource specializing in immunoglobulins (IG), T cell receptors (TR),
      major histocompatibility complex (MHC) and related proteins of the immune system
      (RPI) of human and other vertebrate species, which consists of databases, Web
      resources and interactive on-line tools. IMGT/3Dstructure-DB data are described
      according to the IMGT Scientific chart rules based on the IMGT-ONTOLOGY concepts.
      IMGT/3Dstructure-DB provides IMGT gene and allele identification of IG, TR and
      MHC proteins with known 3D structures, domain delimitations, amino acid positions
      according to the IMGT unique numbering and renumbered coordinate flat files.
      Moreover IMGT/3Dstructure-DB provides 2D graphical representations (or Collier de
      Perles) and results of contact analysis. The IMGT/StructuralQuery tool allows
      search of this database based on specific structural characteristics.
      IMGT/3Dstructure-DB and IMGT/StructuralQuery are freely available at http://imgt.
      cines.fr.

PMID- 14681397
TI  - E-MSD: an integrated data resource for bioinformatics.
AB  - The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/)
      continues to enhance the quality and consistency of macromolecular structure data
      in the Protein Data Bank (PDB) and to work towards the integration of various
      bioinformatics data resources. We have implemented a simple form-based interface
      that allows users to query the MSD directly. The MSD 'atlas pages' show all of
      the information in the MSD for a particular PDB entry. The group has designed new
      search interfaces aimed at specific areas of interest, such as the environment of
      ligands and the secondary structures of proteins. We have also implemented a
      novel search interface that begins to integrate separate MSD search services in a
      single graphical tool. We have worked closely with collaborators to build a new
      visualization tool that can present both structure and sequence data in a unified
      interface, and this data viewer is now used throughout the MSD services for the
      visualization and presentation of search results. Examples showcasing the
      functionality and power of these tools are available from tutorial webpages
      (http://www. ebi.ac.uk/msd-srv/docs/roadshow_tutorial/).

PMID- 14681398
TI  - MODBASE, a database of annotated comparative protein structure models, and
      associated resources.
AB  - MODBASE (http://salilab.org/modbase) is a relational database of annotated
      comparative protein structure models for all available protein sequences matched
      to at least one known protein structure. The models are calculated by MODPIPE, an
      automated modeling pipeline that relies on the MODELLER package for fold
      assignment, sequence-structure alignment, model building and model assessment
      (http:/salilab.org/modeller). MODBASE uses the MySQL relational database
      management system for flexible querying and CHIMERA for viewing the sequences and
      structures (http://www.cgl.ucsf.edu/chimera/). MODBASE is updated regularly to
      reflect the growth in protein sequence and structure databases, as well as
      improvements in the software for calculating the models. For ease of access,
      MODBASE is organized into different data sets. The largest data set contains
      1,26,629 models for domains in 659,495 out of 1,182,126 unique protein sequences
      in the complete Swiss-Prot/TrEMBL database (August 25, 2003); only models based
      on alignments with significant similarity scores and models assessed to have the
      correct fold despite insignificant alignments are included. Another model data
      set supports target selection and structure-based annotation by the New York
      Structural Genomics Research Consortium; e.g. the 53 new structures produced by
      the consortium allowed us to characterize structurally 24,113 sequences. MODBASE
      also contains binding site predictions for small ligands and a set of predicted
      interactions between pairs of modeled sequences from the same genome. Our other
      resources associated with MODBASE include a comprehensive database of multiple
      protein structure alignments (DBALI, http://salilab.org/dbali) as well as web
      servers for automated comparative modeling with MODPIPE (MODWEB, http://salilab.
      org/modweb), modeling of loops in protein structures (MODLOOP,
      http://salilab.org/modloop) and predicting functional consequences of single
      nucleotide polymorphisms (SNPWEB, http://salilab. org/snpweb).

PMID- 14681399
TI  - The distribution and query systems of the RCSB Protein Data Bank.
AB  - The Protein Data Bank (PDB; http://www.pdb.org) is the primary source of
      information on the 3D structure of biological macromolecules. The PDB's mandate
      is to disseminate this information in the most usable form and as widely as
      possible. The current query and distribution system is described and an alpha
      version of the future re-engineered system introduced.

PMID- 14681400
TI  - SCOP database in 2004: refinements integrate structure and sequence family data.
AB  - The Structural Classification of Proteins (SCOP) database is a comprehensive
      ordering of all proteins of known structure, according to their evolutionary and
      structural relationships. Protein domains in SCOP are hierarchically classified
      into families, superfamilies, folds and classes. The continual accumulation of
      sequence and structural data allows more rigorous analysis and provides important
      information for understanding the protein world and its evolutionary repertoire.
      SCOP participates in a project that aims to rationalize and integrate the data on
      proteins held in several sequence and structure databases. As part of this
      project, starting with release 1.63, we have initiated a refinement of the SCOP
      classification, which introduces a number of changes mostly at the levels below
      superfamily. The pending SCOP reclassification will be carried out gradually
      through a number of future releases. In addition to the expanded set of static
      links to external resources, available at the level of domain entries, we have
      started modernization of the interface capabilities of SCOP allowing more dynamic
      links with other databases. SCOP can be accessed at http://scop.mrc
      lmb.cam.ac.uk/scop.

PMID- 14681401
TI  - The SWISS-MODEL Repository of annotated three-dimensional protein structure
      homology models.
AB  - The SWISS-MODEL Repository is a database of annotated three-dimensional
      comparative protein structure models generated by the fully automated homology
      modelling pipeline SWISS-MODEL. The Repository currently contains about 300,000
      three-dimensional models for sequences from the Swiss-Prot and TrEMBL databases.
      The content of the Repository is updated on a regular basis incorporating new
      sequences, taking advantage of new template structures becoming available and
      reflecting improvements in the underlying modelling algorithms. Each entry
      consists of one or more three-dimensional protein models, the superposed template
      structures, the alignments on which the models are based, a summary of the
      modelling process and a force field based quality assessment. The SWISS-MODEL
      Repository can be queried via an interactive website at http://swissmodel.expasy.
      org/repository/. Annotation and cross-linking of the models with other databases,
      e.g. Swiss-Prot on the ExPASy server, allow for seamless navigation between
      protein sequence and structure information. The aim of the SWISS-MODEL Repository
      is to provide access to an up-to-date collection of annotated three-dimensional
      protein models generated by automated homology modelling, bridging the gap
      between sequence and structure databases.

PMID- 14681402
TI  - The SUPERFAMILY database in 2004: additions and improvements.
AB  - The SUPERFAMILY database provides structural assignments to protein sequences and
      a framework for analysis of the results. At the core of the database is a library
      of profile Hidden Markov Models that represent all proteins of known structure.
      The library is based on the SCOP classification of proteins: each model
      corresponds to a SCOP domain and aims to represent an entire superfamily. We have
      applied the library to predicted proteins from all completely sequenced genomes
      (currently 154), the Swiss-Prot and TrEMBL databases and other sequence
      collections. Close to 60% of all proteins have at least one match, and one half
      of all residues are covered by assignments. All models and full results are
      available for download and online browsing at http://supfam.org. Users can study
      the distribution of their superfamily of interest across all completely sequenced
      genomes, investigate with which other superfamilies it combines and retrieve
      proteins in which it occurs. Alternatively, concentrating on a particular genome
      as a whole, it is possible first, to find out its superfamily composition, and
      secondly, to compare it with that of other genomes to detect superfamilies that
      are over- or under-represented. In addition, the webserver provides the following
      standard services: sequence search; keyword search for genomes, superfamilies and
      sequence identifiers; and multiple alignment of genomic, PDB and custom
      sequences.

PMID- 14681403
TI  - SURFACE: a database of protein surface regions for functional annotation.
AB  - The SURFACE (SUrface Residues and Functions Annotated, Compared and Evaluated,
      URL http://cbm.bio.uniroma2.it/surface/) database is a repository of annotated
      and compared protein surface regions. SURFACE contains the results of a large
      scale protein annotation and local structural comparison project. A non-redundant
      set of protein chains is used to build a database of protein surface patches,
      defined as putative surface functional sites. Each patch is annotated with
      sequence and structure-derived information about function or interaction
      abilities. A new procedure for structure comparison is used to perform an all
      versus-all patches comparison. Selection of the results obtained with stringent
      parameters offers a similarity score that can be used to associate different
      patches and allows reliable annotation by similarity. Annotation exerted through
      the comparison of regions of protein surface allows the highlighting of
      similarities that cannot be recognized by other methods of sequence or structure
      comparison. A graphic representation of the surface patches, functional
      annotations and the structural superpositions is available through the web
      interface.

PMID- 14681404
TI  - 3D-GENOMICS: a database to compare structural and functional annotations of
      proteins between sequenced genomes.
AB  - The 3D-GENOMICS database (http://www.sbg.bio. ic.ac.uk/3dgenomics/) provides
      structural annotations for proteins from sequenced genomes. In August 2003 the
      database included data for 93 proteomes. The annotations stored in the database
      include homologous sequences from various sequence databases, domains from SCOP
      and Pfam, patterns from Prosite and other predicted sequence features such as
      transmembrane regions and coiled coils. In addition to annotations at the
      sequence level, several precomputed cross- proteome comparative analyses are
      available based on SCOP domain superfamily composition. Annotations are available
      to the user via a web interface to the database. Multiple points of entry are
      available so that a user is able to: (i) directly access annotations for a single
      protein sequence via keywords or accession codes, (ii) examine a sequence of
      interest chosen from a summary of annotations for a particular proteome, or (iii)
      access precomputed frequency-based cross-proteome comparative analyses.

PMID- 14681405
TI  - TOPS: an enhanced database of protein structural topology.
AB  - The TOPS database holds topological descriptions of protein structures. These
      compact and highly abstract descriptions reduce the protein fold to a sequence of
      Secondary Structure Elements (SSEs) and three sets of pairwise relationships
      between them, hydrogen bonds relating parallel and anti- parallel beta strands,
      spatial adjacencies relating neighbouring SSEs, and the chiralities of selected
      supersecondary structures, including connections in betaalphabeta units and
      between parallel alpha helices. The database is used as a resource for
      visualizing folding topologies, fast topological pattern searching and structure
      comparison. Here, significant enhancements to the TOPS database are described.
      The topological description has been enhanced to include packing relationships
      between helices, which significantly improves the description of protein folds
      with little beta strand content. Further, the topological description has been
      annotated with sequence information. The query interfaces to the database have
      been improved and the new version can be found at http://www.tops.leeds.ac.uk/.

PMID- 14681406
TI  - Genew: the Human Gene Nomenclature Database, 2004 updates.
AB  - Genew, the Human Gene Nomenclature Database http://www.gene.ucl.ac.uk/cgi
      bin/nomenclature/searchgenes.pl is the only resource that provides data for all
      human genes that have approved symbols. It is managed by the HUGO Gene
      Nomenclature Committee (HGNC) as a confidential database, containing over 22 000
      records, 75% of which are represented online by a publicly searchable text file.
      Since 2002, there have been significant improvements to the Genew search engine.
      Additionally we have increased our capacity to analyse confidential sequence
      data, which has enabled us to manage the large numbers of gene symbol requests
      that we receive from the chromosome sequencing consortia.

PMID- 14681407
TI  - The Gene Ontology (GO) database and informatics resource.
AB  - The Gene Ontology (GO) project (http://www. geneontology.org/) provides
      structured, controlled vocabularies and classifications that cover several
      domains of molecular and cellular biology and are freely available for community
      use in the annotation of genes, gene products and sequences. Many model organism
      databases and genome annotation groups use the GO and contribute their annotation
      sets to the GO resource. The GO database integrates the vocabularies and
      contributed annotations and provides full access to this information in several
      formats. Members of the GO Consortium continually work collectively, involving
      outside experts as needed, to expand and update the GO vocabularies. The GO Web
      resource also provides access to extensive documentation about the GO project and
      links to applications that use GO data for functional analyses.

PMID- 14681408
TI  - The Gene Ontology Annotation (GOA) Database: sharing knowledge in Uniprot with
      Gene Ontology.
AB  - The Gene Ontology Annotation (GOA) database (http://www.ebi.ac.uk/GOA) aims to
      provide high-quality electronic and manual annotations to the UniProt
      Knowledgebase (Swiss-Prot, TrEMBL and PIR-PSD) using the standardized vocabulary
      of the Gene Ontology (GO). As a supplementary archive of GO annotation, GOA
      promotes a high level of integration of the knowledge represented in UniProt with
      other databases. This is achieved by converting UniProt annotation into a
      recognized computational format. GOA provides annotated entries for nearly 60,000
      species (GOA-SPTr) and is the largest and most comprehensive open-source
      contributor of annotations to the GO Consortium annotation effort. By integrating
      GO annotations from other model organism groups, GOA consolidates specialized
      knowledge and expertise to ensure the data remain a key reference for up-to-date
      biological information. Furthermore, the GOA database fully endorses the Human
      Proteomics Initiative by prioritizing the annotation of proteins likely to
      benefit human health and disease. In addition to a non-redundant set of
      annotations to the human proteome (GOA-Human) and monthly releases of its GO
      annotation for all species (GOA-SPTr), a series of GO mapping files and specific
      cross-references in other databases are also regularly distributed. GOA can be
      queried through a simple user-friendly web interface or downloaded in a parsable
      format via the EBI and GO FTP websites. The GOA data set can be used to enhance
      the annotation of particular model organism or gene expression data sets,
      although increasingly it has been used to evaluate GO predictions generated from
      text mining or protein interaction experiments. In 2004, the GOA team will build
      on its success and will continue to supplement the functional annotation of
      UniProt and work towards enhancing the ability of scientists to access all
      available biological information. Researchers wishing to query or contribute to
      the GOA project are encouraged to email: goa@ebi.ac.uk.

PMID- 14681409
TI  - The Unified Medical Language System (UMLS): integrating biomedical terminology.
AB  - The Unified Medical Language System (http://umlsks.nlm.nih.gov) is a repository
      of biomedical vocabularies developed by the US National Library of Medicine. The
      UMLS integrates over 2 million names for some 900,000 concepts from more than 60
      families of biomedical vocabularies, as well as 12 million relations among these
      concepts. Vocabularies integrated in the UMLS Metathesaurus include the NCBI
      taxonomy, Gene Ontology, the Medical Subject Headings (MeSH), OMIM and the
      Digital Anatomist Symbolic Knowledge Base. UMLS concepts are not only inter
      related, but may also be linked to external resources such as GenBank. In
      addition to data, the UMLS includes tools for customizing the Metathesaurus
      (MetamorphoSys), for generating lexical variants of concept names (lvg) and for
      extracting UMLS concepts from text (MetaMap). The UMLS knowledge sources are
      updated quarterly. All vocabularies are available at no fee for research purposes
      within an institution, but UMLS users are required to sign a license agreement.
      The UMLS knowledge sources are distributed on CD-ROM and by FTP.

PMID- 14681410
TI  - DEG: a database of essential genes.
AB  - Essential genes are genes that are indispensable to support cellular life. These
      genes constitute a minimal gene set required for a living cell. We have
      constructed a Database of Essential Genes (DEG), which contains all the essential
      genes that are currently available. The functions encoded by essential genes are
      considered a foundation of life and therefore are likely to be common to all
      cells. Users can BLAST the query sequences against DEG. If homologous genes are
      found, it is possible that the queried genes are also essential. Users can search
      for essential genes by their function or name. Users can also browse and extract
      all the records in DEG. Essential gene products comprise excellent targets for
      antibacterial drugs. Analysis of essential genes could help to answer the
      question of what are the basic functions necessary to support cellular life. DEG
      is freely accessible from the website http://tubic.tju.edu.cn/deg/.

PMID- 14681411
TI  - FusionDB: a database for in-depth analysis of prokaryotic gene fusion events.
AB  - FusionDB (http://igs-server.cnrs-mrs.fr/FusionDB/) constitutes a resource
      dedicated to in-depth analysis of bacterial and archaeal gene fusion events. Such
      events can provide the 'Rosetta stone' in the search for potential protein
      protein interactions, as well as metabolic and regulatory networks. However, the
      false positive rate of this approach may be quite high, prompting a detailed
      scrutiny of putative gene fusion events. FusionDB readily provides much of the
      information required for that task. Moreover, FusionDB extends the notion of gene
      fusion from that of a single gene to that of a family of genes by assembling
      pairs of genes from different genomes that belong to the same Cluster of
      Orthogonal Groups (COG). Multiple sequence alignments and phylogenetic tree
      reconstruction for the N- and C-terminal parts of these 'COG fusion' events are
      provided to distinguish single and multiple fusion events from cases of gene
      fission, pseudogenes and other false positives. Finally, gene fusion events with
      matches to known structures of heterodimers in the Protein Data Bank (PDB) are
      identified and may be visualized. FusionDB is fully searchable with access to
      sequence and alignment data at all levels. A number of different scores are
      provided to easily differentiate 'real' from 'questionable' cases, especially
      when larger database searches are performed. FusionDB is cross-linked with the
      'Phylogenomic Display of Bacterial Genes' (PhydBac) online web server. Together,
      these servers provide the complete set of information required for in-depth
      analysis of non-homology-based gene function attribution.

PMID- 14681412
TI  - The KEGG resource for deciphering the genome.
AB  - A grand challenge in the post-genomic era is a complete computer representation
      of the cell and the organism, which will enable computational prediction of
      higher-level complexity of cellular processes and organism behavior from genomic
      information. Toward this end we have been developing a knowledge-based approach
      for network prediction, which is to predict, given a complete set of genes in the
      genome, the protein interaction networks that are responsible for various
      cellular processes. KEGG at http://www.genome.ad.jp/kegg/ is the reference
      knowledge base that integrates current knowledge on molecular interaction
      networks such as pathways and complexes (PATHWAY database), information about
      genes and proteins generated by genome projects (GENES/SSDB/KO databases) and
      information about biochemical compounds and reactions (COMPOUND/GLYCAN/REACTION
      databases). These three types of database actually represent three graph objects,
      called the protein network, the gene universe and the chemical universe. New
      efforts are being made to abstract knowledge, both computationally and manually,
      about ortholog clusters in the KO (KEGG Orthology) database, and to collect and
      analyze carbohydrate structures in the GLYCAN database.

PMID- 14681413
TI  - The ORFanage: an ORFan database.
AB  - As each newly sequenced genome contains a significant number of protein-coding
      ORFs that are species-, family- or lineage-specific, many interesting questions
      arise about the evolution and role of these ORFs and of the genomes they are part
      of. We refer to these poorly conserved ORFs as singleton or paralogous ORFans if
      they are unique to one genome, or as orthologous ORFans if they appear only in a
      family of closely related organisms and have no homolog in other genomes. In
      order to study and classify ORFans we have constructed the ORFanage, an ORFan
      database. This database consists of the predicted ORFs in fully sequenced
      microbial genomes, and enables searching for the three types of ORFans in any
      subset of the genomes chosen by the user. The ORFanage could help in choosing
      interesting targets for further genomic and evolutionary studies. The ORFanage is
      accessible via http://www.bioinformatics.buffalo. edu/ORFanage.

PMID- 14681414
TI  - TransportDB: a relational database of cellular membrane transport systems.
AB  - TransportDB (http://www.membranetransport.org) is a relational database designed
      for describing the predicted cellular membrane transport proteins in organisms
      whose complete genome sequences are available. For each organism, the complete
      set of membrane transport systems was identified and classified into different
      types and families according to putative membrane topology, protein family,
      bioenergetics and substrate specificities. Web pages were created to provide user
      friendly interfaces to easily access, query and download the data. Additional
      features, such as a BLAST search tool against known transporter protein
      sequences, comparison of transport systems from different organisms and
      phylogenetic trees of individual transporter families are also provided.
      TransportDB will be regularly updated with data obtained from newly sequenced
      genomes.

PMID- 14681415
TI  - VirGen: a comprehensive viral genome resource.
AB  - VirGen is a comprehensive viral genome resource that organizes the 'sequence
      space' of viral genomes in a structured fashion. It has been developed with the
      objective of serving as an annotated and curated database comprising complete
      genome sequences of viruses, value-added derived data and data mining tools. The
      current release (v1.1) contains 559 complete genomes in addition to 287 putative
      genomes of viruses belonging to eight viral families for which the host range
      includes animals and plants. Viral genomes in VirGen are annotated using sequence
      based Bioinformatics approaches. The genomic data is also curated to identify
      'alternate names' of viral proteins, where available. VirGen archives the results
      of comparisons of genomes, proteomes and individual proteins within and between
      viral species. It is the first resource to provide phylogenetic trees of viral
      species computed using whole-genome sequence data. The module of predicted B-cell
      antigenic determinants in VirGen is an attempt to link the genome to its
      vaccinome. Comparative genome analysis data facilitate the study of genome
      organization and evolution of viruses, which would have implications in applied
      research to identify candidates for the design of vaccines and antiviral drugs.
      VirGen is a relational database and is available at http://bioinfo.
      ernet.in/virgen/virgen.html.

PMID- 14681416
TI  - The CyberCell Database (CCDB): a comprehensive, self-updating, relational
      database to coordinate and facilitate in silico modeling of Escherichia coli.
AB  - The CyberCell Database (CCDB: http://redpoll. pharmacy.ualberta.ca/CCDB) is a
      comprehensive, web-accessible database designed to support and coordinate
      international efforts in modeling an Escherichia coli cell on a computer. The
      CCDB brings together both observed and derived quantitative data from numerous
      independent sources covering many aspects of the genomic, proteomic and
      metabolomic character of E.coli (strain K12). The database is self-updating but
      also supports 'community' annotation, and provides an extensive array of viewing,
      querying and search options including a powerful, easy-to-use relational data
      extraction system.

PMID- 14681417
TI  - coliBASE: an online database for Escherichia coli, Shigella and Salmonella
      comparative genomics.
AB  - We have constructed coliBASE, a database for Escherichia coli, Shigella and
      Salmonella comparative genomics available online at http://colibase. bham.ac.uk.
      Unlike other E.coli databases, which focus on the laboratory model strain K12,
      coliBASE is intended to reflect the full diversity of E.coli and its relatives.
      The database contains comparative data including whole genome alignments and
      lists of putative orthologous genes, together with numerous analytical tools and
      links to existing online resources. The data are stored in a relational database,
      accessible by a number of user-friendly search methods and graphical browsers.
      The database schema is generic and can easily be applied to other bacterial
      genomes. Two such databases, CampyDB (for the analysis of Campylobacter spp.) and
      ClostriDB (for Clostridium spp.) are also available at http://campy.bham.ac.uk
      and http://clostri. bham.ac.uk, respectively. An example of the power of E.coli
      comparative analyses such as those available through coliBASE is presented.

PMID- 14681418
TI  - GenProtEC: an updated and improved analysis of functions of Escherichia coli K-12
      proteins.
AB  - Using more than one approach to characterizing functions of unknown proteins, we
      now present in GenProtEC (http://genprotec.mbl.edu/) some level of function
      information for 87% of Escherichia coli K-12 proteins. A new approach that has
      yielded new information entails assigning content of structural domains and their
      functions to E.coli proteins. In addition, some earlier methods have been further
      refined to provide more meaningful data. The process of identifying and
      separating multimodular or fused proteins into component modules has been
      improved. As a result, groups of sequence-similar (paralogous) proteins have been
      refined. Experimental information from recent literature on previously unknown
      genes has been incorporated. We now use a rich system of characterizing cell
      roles which accents the fact that many proteins play more than one cellular role
      and therefore carry more than one designation from our detailed catalog of roles,
      MultiFun.

PMID- 14681419
TI  - RegulonDB (version 4.0): transcriptional regulation, operon organization and
      growth conditions in Escherichia coli K-12.
AB  - RegulonDB is the primary database of the major international maintained curation
      of original literature with experimental knowledge about the elements and
      interactions of the network of transcriptional regulation in Escherichia coli K
      12. This includes mechanistic information about operon organization and their
      decomposition into transcription units (TUs), promoters and their sigma type,
      binding sites of specific transcriptional regulators (TRs), their organization
      into 'regulatory phrases', active and inactive conformations of TRs, as well as
      terminators and ribosome binding sites. The database is complemented with clearly
      marked computational predictions of TUs, promoters and binding sites of TRs. The
      current version has been expanded to include information beyond specific
      mechanisms aimed at gathering different growth conditions and the associated
      induced and/or repressed genes. RegulonDB is now linked with Swiss-Prot, with
      microarray databases, and with a suite of programs to analyze and visualize
      microarray experiments. We provide a summary of the biological knowledge
      contained in RegulonDB and describe the major changes in the design of the
      database. RegulonDB can be accessed on the web at the URL:
      http://www.cifn.unam.mx/Computational_Biology/regulondb/.

PMID- 14681420
TI  - MolliGen, a database dedicated to the comparative genomics of Mollicutes.
AB  - Bacteria belonging to the class Mollicutes were among the first ones to be
      selected for complete genome sequencing because of the minimal size of their
      genomes and their pathogenicity for humans and a broad range of animals and
      plants. At this time six genome sequences have been publicly released (Mycoplasma
      genitalium, Mycoplasma pneumoniae, Ureaplasma urealyticum-parvum, Mycoplasma
      pulmonis, Mycoplasma penetrans and Mycoplasma gallisepticum) and as the number of
      available mollicute genomes increases, comparative genomics analysis within this
      model group of organisms becomes more and more instructive. However, such an
      analysis is difficult to carry out without a suitable platform gathering not only
      the original annotations but also relevant information available in public
      databases or obtained by applying common bioinformatics methods. With the aim of
      solving these difficulties, we have developed a web-accessible database named
      MolliGen (http://cbi.labri.fr/outils/molligen/). After selecting a set of genomes
      the user can launch various types of search based on annotation, position on the
      chromosomes or sequence similarity. In addition, relationships of putative
      orthology have been precomputed to allow differential genome queries. The results
      are presented in table format with multiple links to public databases and to
      bioinformatic analyses such as multiple alignments or BLAST search. Specific
      tools were also developed for the graphical visualization of the results,
      including a multi- genome browser for displaying dynamic pictures with clickable
      objects and for viewing relationships of precomputed similarity. MolliGen is
      designed to integrate all the complete genomes of mollicutes as they become
      available.

PMID- 14681421
TI  - Saccharomyces Genome Database (SGD) provides tools to identify and analyze
      sequences from Saccharomyces cerevisiae and related sequences from other
      organisms.
AB  - The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/), a
      scientific database of the molecular biology and genetics of the yeast
      Saccharomyces cerevisiae, has recently developed several new resources that allow
      the comparison and integration of information on a genome-wide scale, enabling
      the user not only to find detailed information about individual genes, but also
      to make connections across groups of genes with common features and across
      different species. The Fungal Alignment Viewer displays alignments of sequences
      from multiple fungal genomes, while the Sequence Similarity Query tool displays
      PSI-BLAST alignments of each S.cerevisiae protein with similar proteins from any
      species whose sequences are contained in the non-redundant (nr) protein data set
      at NCBI. The Yeast Biochemical Pathways tool integrates groups of genes by their
      common roles in metabolism and displays the metabolic pathways in a graphical
      form. Finally, the Find Chromosomal Features search interface provides a
      versatile tool for querying multiple types of information in SGD.

PMID- 14681422
TI  - Genolevures: comparative genomics and molecular evolution of hemiascomycetous
      yeasts.
AB  - The Genolevures online database (http://cbi.labri.fr/Genolevures/) provides data
      and tools to facilitate comparative genomic studies on hemiascomycetous yeasts.
      Now, four complete genome sequences recently determined (Candida glabrata,
      Kluyveromyces lactis, Debaryomyces hansenii, Yarrowia lipolytica) have been added
      to the partial sequences of 13 species previously analysed by a random approach.
      The database also includes the reference genome Saccharomyces cerevisiae. Data
      are presented with a focus on relations between genes and genomes: conservation
      of genes and gene families, speciation, chromosomal reorganization and synteny.
      The Genolevures site includes a community area for specific studies by members of
      the international community.

PMID- 14681423
TI  - SCMD: Saccharomyces cerevisiae Morphological Database.
AB  - To study the global regulation of cell morphology, a number of groups have
      recently reported genome-wide screening data for yeast mutants with abnormal
      morphology. Despite the relatively simple ellipsoidal shape of yeast cells, in
      the past, cell morphology researchers have processed information on cells
      manually. These time-consuming, entirely subjective tasks motivated us to develop
      image-processing software that automatically extracts yeast cells from
      micrographs and processes them to measure key morphological characteristics such
      as cell size, roundness, bud neck position angle, nuclear DNA localization and
      actin localization. To date, we have retrieved 960,609 cells from 52,988
      micrographs of 2531 mutants using our software, and we have published the results
      in the Saccharomyces cerevisiae Morphological Database (SCMD), which facilitates
      the analysis of abnormal cells. Our system provides quantitative data for shapes
      of the daughter and mother cells, localization of the nuclear DNA and morphology
      of the actin patches. To search for mutants with similar morphological traits,
      the system outputs a list of mutants ranked by similarity of average
      morphological parameters. The SCMD is available at http://yeast. gi.k.u
      tokyo.ac.jp/.

PMID- 14681424
TI  - yMGV: a cross-species expression data mining tool.
AB  - The yeast Microarray Global Viewer (yMGV @ http://transcriptome.ens.fr/ymgv) was
      created 3 years ago as a database that houses a collection of Saccharomyces
      cerevisiae and Schizosaccharo myces pombe microarray data sets published in 82
      different articles. yMGV couples data mining tools with a user-friendly web
      interface so that, with a few mouse clicks, one can identify the conditions that
      affect the expression of a gene or list of genes regulated in a set of
      experiments. One of the major new features we present here is a set of tools that
      allows for inter-organism comparisons. This should enable the fission yeast
      community to take advantage of the large amount of available information on
      budding yeast transcriptome. New tools and ongoing developments are also
      presented here.

PMID- 14681425
TI  - ApiEST-DB: analyzing clustered EST data of the apicomplexan parasites.
AB  - ApiEST-DB (http://www.cbil.upenn.edu/paradbs-servlet/) provides integrated access
      to publicly available EST data from protozoan parasites in the phylum
      Apicomplexa. The database currently incorporates a total of nearly 100,000 ESTs
      from several parasite species of clinical and/or veterinary interest, including
      Eimeria tenella, Neospora caninum, Plasmodium falciparum, Sarcocystis neurona and
      Toxoplasma gondii. To facilitate analysis of these data, EST sequences were
      clustered and assembled to form consensus sequences for each organism, and these
      assemblies were then subjected to automated annotation via similarity searches
      against protein and domain databases. The underlying relational database
      infrastructure, Genomics Unified Schema (GUS), enables complex biologically based
      queries, facilitating validation of gene models, identification of alternative
      splicing, detection of single nucleotide polymorphisms, identification of stage
      specific genes and recognition of phylogenetically conserved and phylogenetically
      restricted sequences.

PMID- 14681426
TI  - CryptoDB: the Cryptosporidium genome resource.
AB  - CryptoDB (http://CryptoDB.org) represents a collaborative effort to locate all
      genome data for the apicomplexan parasite Cryptosporidium parvum in a single user
      friendly database. CryptoDB currently houses the genomic sequence data for both
      the human type 1 H strain and the bovine type 2 IOWA strain in addition to all
      other available EST and GSS sequences obtained from public repositories. All data
      are available for data mining via BLAST, keyword searches of pre-computed BLASTX
      results and user-defined or PROSITE motif pattern searches. Release 1.0 of
      CryptoDB contains approximately 19 million bases of genome sequence for the H and
      IOWA strains and an additional approximately 24 million bases of GSS and EST
      sequence obtained from other sources. Open reading frames greater than 50 and 100
      amino acids have been generated for all sequences and all data are available for
      bulk download. This database, like other apicomplexan parasite databases, has
      been built utilizing the PlasmoDB model.

PMID- 14681427
TI  - dictyBase: a new Dictyostelium discoideum genome database.
AB  - Dictyostelium discoideum is a powerful and genetically tractable model system
      used for the study of numerous cellular molecular mechanisms including
      chemotaxis, phagocytosis and signal transduction. The past 2 years have seen a
      significant expansion in the scope and accessibility of online resources for
      Dictyostelium. Recent advances have focused on the development of a new
      comprehensive online resource called dictyBase (http://dictybase.org). This
      database not only provides access to genomic data including functional annotation
      of genes, gene products and chromosomal mapping, but also to extensive biological
      information such as mutant phenotypes and corresponding reference material. In
      conjunction with additional sites (http://genome. imb-jena.de/dictyostelium/,
      http://dictyensembl. bioch.bcm.tmc.edu and
      http://www.sanger.ac.uk/Projects/D_discoideum/) from the genome sequencing and
      assembly centers, these improvements have expanded the scope of the Dictyostelium
      databases making them accessible and useful to any researcher interested in
      comparative and functional genomics in metazoan organisms.

PMID- 14681428
TI  - Full-malaria 2004: an enlarged database for comparative studies of full-length
      cDNAs of malaria parasites, Plasmodium species.
AB  - Full-malaria (http://fullmal.ims.u-tokyo.ac.jp), a database for full-length cDNAs
      from the human malaria parasite, Plasmodium falciparum has been updated in at
      least three points. (i) We added 8934 sequences generated from the addition of
      new libraries, so that our collection of 11,424 full-length cDNAs covers 1375
      (25%) of the estimated number of the entire 5409 parasite genes. (ii) All of our
      full-length cDNAs and GenBank EST sequences were mapped to genomic sequences
      together with publicly available annotated genes and other predictions. This
      precisely determined the gene structures and positions of the transcriptional
      start sites, which are indispensable for the identification of the promoter
      regions. (iii) A total of 4257 cDNA sequences were newly generated from murine
      malaria parasites, Plasmodium yoelii yoelii. The genome/cDNA sequences were
      compared at both nucleotide and amino acid levels, with those of P.falciparum,
      and the sequence alignment for each gene is presented graphically. This part of
      the database serves as a versatile platform to elucidate the function(s) of
      malaria genes by a comparative genomic approach. It should also be noted that all
      of the cDNAs represented in this database are supported by physical cDNA clones,
      which are publicly and freely available, and should serve as indispensable
      resources to explore functional analyses of malaria genomes.

PMID- 14681429
TI  - GeneDB: a resource for prokaryotic and eukaryotic organisms.
AB  - GeneDB (http://www.genedb.org/) is a genome database for prokaryotic and
      eukaryotic organisms. The resource provides a portal through which data generated
      by the Pathogen Sequencing Unit at the Wellcome Trust Sanger Institute and other
      collaborating sequencing centres can be made publicly available. It combines data
      from finished and ongoing genome and expressed sequence tag (EST) projects with
      curated annotation, that can be searched, sorted and downloaded, using a single
      web based resource. The current release stores 11 datasets of which six are
      curated and maintained by biologists, who review and incorporate information from
      the scientific literature, public databases and the respective research
      communities.

PMID- 14681430
TI  - TcruziDB: an integrated Trypanosoma cruzi genome resource.
AB  - TcruziDB (http://TcruziDB.org) is an integrated genome database for the parasitic
      organism Trypanosoma cruzi, the causative agent of Chagas' disease. The database
      currently incorporates all available sequence data (Genomic, BAC, EST) in a
      single user-friendly location. The database contains a variety of tools
      specifically designed for searching unannotated draft sequence via BLAST, keyword
      searches of pre-computed BLAST results, and protein motif searches. Release 1.0
      of the database contains nearly 730 million bp of genome sequence from 1.1
      million sequence reads generated by the TIGR-Karolinska-SBRI Trypanosoma cruzi
      Genome Consortium and 15 million bp of clustered EST and genomic sequence
      obtained from other sources. As annotation, microarray and proteomic data become
      available, the database will incorporate and integrate these data using the GUS
      (http://www.gusdb. org) relational framework.

PMID- 14681431
TI  - FLAGdb++: a database for the functional analysis of the Arabidopsis genome.
AB  - FLAGdb++ is dedicated to the integration and visualization of data for high
      throughput functional analysis of a fully sequenced genome, as illustrated for
      Arabidopsis. FLAGdb++ displays the predicted or experimental data in a position
      dependent way and displays correlations and relationships between different
      features. FLAGdb++ provides for a given genome region, summarized characteristics
      of experimental materials like probe lengths, locations and specificities having
      an impact upon the confidence we will put in the experimental results. A selected
      subset of the available information is linked to a locus represented on an easy
      to-interpret and memorable graphical display. Data are curated, processed and
      formatted before their integration into FLAGdb++. FLAGdb++ contains different
      options for easy back and forth navigation through many loci selected at the
      start of a session. It includes an original two-component visualization of the
      data, a genome-wide and a local view, which are permanently linked and display
      complementary information. Density curves along the chromosomes may be displayed
      in parallel for suggesting correlations between different structural and
      functional data. FLAGdb++ is fully accessible at http://genoplante
      info.infobiogen.fr/FLAGdb/.

PMID- 14681432
TI  - PHYTOPROT: a database of clusters of plant proteins.
AB  - All the protein sequences from plants (including Arabidopsis thaliana) available
      from SwissProt/TrEMBL have been the subject of an all-by-all systematic
      comparison and grouped into clusters of related proteins. Within each cluster,
      the sequences have been submitted to pyramidal classification; in the case where
      two or several subfamilies have been grouped together, the pyramidal tree helps
      in finding which sequences make the links between subfamilies. In addition, the
      'domains' that are common to two or more sequences within a cluster were
      determined and displayed a la ProDom. The resulting graphical representations
      proved to be quite efficient in pinpointing those protein sequences suffering
      from a probable error in the annotation of their genes. The clusters can be
      searched through various criteria and their pyramidal classifications and their
      domain representations can be displayed by querying http://genoplante-info.
      infobiogen.fr/phytoprot. The user can also launch a BLAST search of a query
      sequence against all the clusters.

PMID- 14681433
TI  - PlantGDB, plant genome database and analysis tools.
AB  - PlantGDB (http://www.plantgdb.org/) is a database of molecular sequence data for
      all plant species with significant sequencing efforts. The database organizes EST
      sequences into contigs that represent tentative unique genes. Contigs are
      annotated and, whenever possible, linked to their respective genomic DNA. Genome
      sequence fragments are assembled similarly. The goal of the PlantGDB web site is
      to establish the basis for identifying sets of genes common to all plants or
      specific to particular species by integrating a number of bioinformatics tools
      that facilitate gene prediction and cross- species comparisons. For species with
      large-scale genome sequencing efforts, PlantGDB provides genome browsing
      capabilities that integrate all available EST and cDNA evidence for current gene
      models (for Arabidopsis thaliana, see the AtGDB site at
      http://www.plantgdb.org/AtGDB/).

PMID- 14681434
TI  - The TIGR Plant Repeat Databases: a collective resource for the identification of
      repetitive sequences in plants.
AB  - In a number of higher plants, a substantial portion of the genome is composed of
      repetitive sequences that can hinder genome annotation and sequencing efforts. To
      better understand the nature of repetitive sequences in plants and provide a
      resource for identifying such sequences, we constructed databases of repetitive
      sequences for 12 plant genera: Arabidopsis, Brassica, Glycine, Hordeum, Lotus,
      Lycopersicon, Medicago, Oryza, Solanum, Sorghum, Triticum and Zea
      (www.tigr.org/tdb/e2k1/plant. repeats/index.shtml). The repetitive sequences
      within each database have been coded into super-classes, classes and sub-classes
      based on sequence and structure similarity. These databases are available for
      sequence similarity searches as well as downloadable files either as entire
      databases or subsets of each database. To further the utility for comparative
      studies and to provide a resource for searching for repetitive sequences in other
      genera within these families, repetitive sequences have been combined into four
      databases to represent the Brassicaceae, Fabaceae, Gramineae and Solanaceae
      families. Collectively, these databases provide a resource for the
      identification, classification and analysis of repetitive sequences in plants.

PMID- 14681435
TI  - TropGENE-DB, a multi-tropical crop information system.
AB  - TropGENE-DB, is a crop information system created to store genetic, molecular and
      phenotypic data of the numerous yet poorly documented tropical crop species. The
      most common data stored in TropGENE-DB are information on genetic resources (agro
      morphological data, parentages, allelic diversity), molecular markers, genetic
      maps, results of quantitative trait loci analyses, data from physical mapping,
      sequences, genes, as well as the corresponding references. TropGENE-DB is
      organized on a crop basis with currently three running modules (sugarcane, cocoa
      and banana), with plans to create additional modules for rice, cotton, oil palm,
      coconut, rubber tree, pineapple, taro, yam and sorghum. The TropGENE-DB
      information system is accessible for consultation via the internet at
      http://tropgenedb.cirad.fr. Specific web consultation interfaces have been
      designed to allow quick consultations as well as complex queries.

PMID- 14681436
TI  - AthaMap: an online resource for in silico transcription factor binding sites in
      the Arabidopsis thaliana genome.
AB  - Gene expression is controlled mainly by the binding of transcription factors to
      regulatory sequences. To generate a genomic map for regulatory sequences, the
      Arabidopsis thaliana genome was screened for putative transcription factor
      binding sites. Using publicly available data from the TRANSFAC database and from
      publications, alignment matrices for 23 transcription factors of 13 different
      factor families were used with the pattern search program Patser to determine the
      genomic positions of more than 2.4 x 10(6) putative binding sites. Due to the
      dense clustering of genes and the observation that regulatory sequences are not
      restricted to upstream regions, the prediction of binding sites was performed for
      the whole genome. The genomic positions and the underlying data were imported
      into the newly developed AthaMap database. This data can be accessed by
      positional information or the Arabidopsis Genome Initiative identification
      number. Putative binding sites are displayed in the defined region. Data on the
      matrices used and on the thresholds applied in these screens are given in the
      database. Considering the high density of sites it will be a valuable resource
      for generating models on gene expression regulation. The data are available at
      http://www.athamap.de.

PMID- 14681437
TI  - MIPS Arabidopsis thaliana Database (MAtDB): an integrated biological knowledge
      resource for plant genomics.
AB  - Arabidopsis thaliana is the most widely studied model plant. Functional genomics
      is intensively underway in many laboratories worldwide. Beyond the basic
      annotation of the primary sequence data, the annotated genetic elements of
      Arabidopsis must be linked to diverse biological data and higher order
      information such as metabolic or regulatory pathways. The MIPS Arabidopsis
      thaliana database MAtDB aims to provide a comprehensive resource for Arabidopsis
      as a genome model that serves as a primary reference for research in plants and
      is suitable for transfer of knowledge to other plants, especially crops. The
      genome sequence as a common backbone serves as a scaffold for the integration of
      data, while, in a complementary effort, these data are enhanced through the
      application of state-of-the-art bioinformatics tools. This information is
      visualized on a genome-wide and a gene-by-gene basis with access both for web
      users and applications. This report updates the information given in a previous
      report and provides an outlook on further developments. The MAtDB web interface
      can be accessed at http://mips.gsf.de/proj/thal/db.

PMID- 14681438
TI  - BGI-RIS: an integrated information resource and comparative analysis workbench
      for rice genomics.
AB  - Rice is a major food staple for the world's population and serves as a model
      species in cereal genome research. The Beijing Genomics Institute (BGI) has long
      been devoting itself to sequencing, information analysis and biological research
      of the rice and other crop genomes. In order to facilitate the application of the
      rice genomic information and to provide a foundation for functional and
      evolutionary studies of other important cereal crops, we implemented our Rice
      Information System (BGI-RIS), the most up-to-date integrated information resource
      as well as a workbench for comparative genomic analysis. In addition to
      comprehensive data from Oryza sativa L. ssp. indica sequenced by BGI, BGI-RIS
      also hosts carefully curated genome information from Oryza sativa L. ssp.
      japonica and EST sequences available from other cereal crops. In this resource,
      sequence contigs of indica (93-11) have been further assembled into Mbp-sized
      scaffolds and anchored onto the rice chromosomes referenced to physical/genetic
      markers, cDNAs and BAC-end sequences. We have annotated the rice genomes for gene
      content, repetitive elements, gene duplications (tandem and segmental) and single
      nucleotide polymorphisms between rice subspecies. Designed as a basic platform,
      BGI-RIS presents the sequenced genomes and related information in systematic and
      graphical ways for the convenience of in-depth comparative studies
      (http://rise.genomics.org.cn/).

PMID- 14681439
TI  - The Rice PIPELINE: a unification tool for plant functional genomics.
AB  - The Rice Genome Research Project in Japan performs genome sequencing and
      comprehensive expression profiling, constructs genetic and physical maps,
      collects full-length cDNAs and generates mutant lines, all aimed at improving the
      breeding of the rice plant as a food source. The National Institute of
      Agrobiological Sciences in Tsukuba, Japan, has accumulated numerous rice
      biological resources and has already successfully produced a high-quality genome
      sequence, a high-density genetic map with 3000 markers, 30,000 full-length cDNAs,
      over 700 expression profiles with a 9000 cDNA microarray and 15,000 flanking
      sequences with Tos17 insertions in about 3765 mutant lines from about 50,000
      transposon insertion lines. These resources are available in the public domain. A
      new unification tool for functional genomics, called Rice PIPELINE, has also been
      developed for the dynamic collection and compilation of genomics data (genome
      sequences, full-length cDNAs, gene expression profiles, mutant lines, cis
      elements) from various databases. The mission of Rice PIPELINE is to provide a
      unique scientific resource that pools publicly available rice genomic data for
      search by clone sequence, clone name, GenBank accession number, or keyword. The
      web-based form of Rice PIPELINE is available at
      http://cdna01.dna.affrc.go.jp/PIPE/.

PMID- 14681440
TI  - Rice Proteome Database based on two-dimensional polyacrylamide gel
      electrophoresis: its status in 2003.
AB  - The Rice Proteome Database is the first detailed database to describe the
      proteome of rice. The current release contains 21 reference maps based on two
      dimensional polyacrylamide gel electrophoresis (2D-PAGE) of proteins from rice
      tissues and subcellular compartments. These reference maps comprise 11 941
      identified proteins showing tissue and subcellular localization, corresponding to
      4180 separate protein entries in the database. The Rice Proteome Database
      contains the calculated properties of each protein such as molecular weight,
      isoelectric point and expression; experimentally determined properties such as
      amino acid sequences obtained using protein sequencers and mass spectrometry; and
      the results of database searches such as sequence homologies. The database is
      searchable by keyword, accession number, protein name, isoelectric point,
      molecular weight and amino acid sequence, or by selection of a spot on one of the
      2D-PAGE reference maps. Cross-references are provided to tools for proteomics and
      to other 2D-PAGE databases, which in turn provide many links to other molecular
      databases. The information in the Rice Proteome Database is updated weekly, and
      is available on the World Wide Web at http://gene64.dna.affrc.go.jp/RPD/.

PMID- 14681441
TI  - MaizeGDB, the community database for maize genetics and genomics.
AB  - The Maize Genetics and Genomics Database (MaizeGDB) is a central repository for
      maize sequence, stock, phenotype, genotypic and karyotypic variation, and
      chromosomal mapping data. In addition, MaizeGDB provides contact information for
      over 2400 maize cooperative researchers, facilitating interactions between
      members of the rapidly expanding maize community. MaizeGDB represents the
      synthesis of all data available previously from ZmDB and from MaizeDB-databases
      that have been superseded by MaizeGDB. MaizeGDB provides web-based tools for
      ordering maize stocks from several organizations including the Maize Genetics
      Cooperation Stock Center and the North Central Regional Plant Introduction
      Station (NCRPIS). Sequence searches yield records displayed with embedded links
      to facilitate ordering cloned sequences from various groups including the Maize
      Gene Discovery Project and the Clemson University Genomics Institute. An
      intuitive web interface is implemented to facilitate navigation between related
      data, and analytical tools are embedded within data displays. Web-based curation
      tools for both designated experts and general researchers are currently under
      development. MaizeGDB can be accessed at http://www.maizegdb.org/.

PMID- 14681442
TI  - SGMD: the Soybean Genomics and Microarray Database.
AB  - The Soybean Genomics and Microarray Database (SGMD) attempts to provide an
      integrated view of the interaction of soybean with the soybean cyst nematode and
      contains genomic, EST and microarray data with embedded analytical tools allowing
      correlation of soybean ESTs with their gene expression profiles. SGMD provides
      analytical tools to mine the microarray data quickly by integrating many analysis
      methods within the database itself. The expression profiles of genes at time
      intervals during the first 8 days of nematode invasion is searchable by gene name
      or GenBank accession number. Recent developments include the addition of a
      searchable database for soybean cyst nematode ESTs and photographs of the
      invasion process at time points examined using microarrays. SGMD is completely
      accessible from the web at: http://psi081.ba.ars.usda.gov/SGMD/default.htm.

PMID- 14681443
TI  - CADRE: the Central Aspergillus Data REpository.
AB  - CADRE is a public resource for housing and analysing genomic data extracted from
      species of Aspergillus. It arose to enable maintenance of the complete annotated
      genomic sequence of Aspergillus fumigatus and to provide tools for searching,
      analysing and visualizing features of fungal genomes. By implementing CADRE using
      Ensembl, a framework is in place for storing and comparing several genomes: the
      resource will thus expand by including other Aspergillus genomes (such as
      Aspergillus nidulans) as they become available. CADRE is accessible at
      http://www.cadre. man.ac.uk.

PMID- 14681444
TI  - RNAiDB and PhenoBlast: web tools for genome-wide phenotypic mapping projects.
AB  - RNA interference (RNAi) is being used in large-scale genomic studies as a rapid
      way to obtain in vivo functional information associated with specific genes. How
      best to archive and mine the complex data derived from these studies provides a
      series of challenges associated with both the methods used to elicit the RNAi
      response and the functional data gathered. RNAiDB (RNAi Database; http://www.
      rnai.org) has been created for the archival, distribution and analysis of
      phenotypic data from large-scale RNAi analyses in Caenorhabditis elegans. The
      database contains a compendium of publicly available data and provides
      information on experimental methods and phenotypic results, including raw data in
      the form of images and streaming time-lapse movies. Phenotypic summaries together
      with graphical displays of RNAi to gene mappings allow quick intuitive comparison
      of results from different RNAi assays and visualization of the gene product(s)
      potentially inhibited by each RNAi experiment based on multiple sequence analysis
      methods. RNAiDB can be searched using combinatorial queries and using the novel
      tool PhenoBlast, which ranks genes according to their overall phenotypic
      similarity. RNAiDB could serve as a model database for distributing and
      navigating in vivo functional information from large-scale systematic phenotypic
      analyses in different organisms.

PMID- 14681445
TI  - WormBase: a multi-species resource for nematode biology and genomics.
AB  - WormBase (http://www.wormbase.org/) is the central data repository for
      information about Caenorhabditis elegans and related nematodes. As a model
      organism database, WormBase extends beyond the genomic sequence, integrating
      experimental results with extensively annotated views of the genome. The WormBase
      Consortium continues to expand the biological scope and utility of WormBase with
      the inclusion of large-scale genomic analyses, through active data and literature
      curation, through new analysis and visualization tools, and through refinement of
      the user interface. Over the past year, the nearly complete genomic sequence and
      comparative analyses of the closely related species Caenorhabditis briggsae have
      been integrated into WormBase, including gene predictions, ortholog assignments
      and a new synteny viewer to display the relationships between the two species.
      Extensive site-wide refinement of the user interface now provides quick access to
      the most frequently accessed resources and a consistent browsing experience
      across the site. Unified single-page views now provide complete summaries of
      commonly accessed entries like genes. These advances continue to increase the
      utility of WormBase for C.elegans researchers, as well as for those researchers
      exploring problems in functional and comparative genomics in the context of a
      powerful genetic system.

PMID- 14681446
TI  - Flytrap, a database documenting a GFP protein-trap insertion screen in Drosophila
      melanogaster.
AB  - Flytrap is a web-enabled relational database of transposable element insertions
      in Drosophila melanogaster. A green fluorescent protein (GFP) artificial exon
      carried by a transposable P-element is mobilized and inserted into a host gene
      intron creating a GFP fusion protein. The sequence of the tagged gene is
      determined by sequencing inverse-PCR products derived from genomic DNA. Flytrap
      contains two principle data types: micrographs of protein localization and a
      cellular component ontology, based on rules derived from the Gene Ontology
      consortium (http://www.geneontology.org), describing protein localization.
      Flytrap also has links to gene information contained in Flybase (http://
      flybase.bio.indiana.edu). The system is designed to accept submissions of
      micrographs and descriptions from any type of tissue (e.g. wing imaginal disk,
      ovary) and at any stage of development. Insertion lines can be searched using a
      number of queries, including Berkeley Drosophila Genome Project (BDGP) numbers
      and protein localization. In addition, Flytrap provides online order forms linked
      to each insertion line so that users may request any line generated from this
      project. Flytrap may be accessed from the homepage at http://flytrap.med.
      yale.edu.

PMID- 14681447
TI  - AppaDB: an AcedB database for the nematode satellite organism Pristionchus
      pacificus.
AB  - Pristionchus pacificus is a free-living nematode of the Diplogastridae family and
      was recently developed as a satellite system in evolutionary developmental
      biology. AppaDB, a P.pacificus database, was created (http://appadb.eb.tuebingen.
      mpg.de) to integrate the genomic data of P.pacificus, comprising the physical
      map, genetic linkage map, EST and BAC end sequence and hybridization data. This
      developing database serves as a repository to search and find any information
      regarding physical contigs or genetic markers required for mapping of mutants.
      Additionally, it provides a platform for the Caenorhabditis elegans community to
      compare nematode genetic data in an evolutionary perspective.

PMID- 14681448
TI  - Nematode.net: a tool for navigating sequences from parasitic and free-living
      nematodes.
AB  - Nematode.net (www.nematode.net) is a web- accessible resource for investigating
      gene sequences from nematode genomes. The database is an outgrowth of the
      parasitic nematode EST project at Washington University's Genome Sequencing
      Center (GSC), St Louis. A sister project at the University of Edinburgh and the
      Sanger Institute is also underway. More than 295,000 ESTs have been generated
      from >30 nematodes other than Caenorhabditis elegans including key parasites of
      humans, animals and plants. Nematode.net currently provides NemaGene EST cluster
      consensus sequence, enhanced online BLAST search tools, functional
      classifications of cluster sequences and comprehensive information concerning the
      ongoing generation of nematode genome data. The long-term goal of nematode.net is
      to provide the scientific community with the highest quality sequence information
      and tools for studying these diverse species.

PMID- 14681449
TI  - NEMBASE: a resource for parasitic nematode ESTs.
AB  - NEMBASE (available at http://www.nematodes.org) is a publicly available online
      database providing access to the sequence and associated meta-data currently
      being generated as part of the Edinburgh-Wellcome Trust Sanger Institute
      parasitic nematode EST project. NEMBASE currently holds approximately 100 000
      sequences from 10 different species of nematode. To facilitate ease of use,
      sequences have been processed to generate a non-redundant set of gene objects
      ('partial genome') for each species. Users may query the database on the basis of
      BLAST annotation, sequence similarity or expression profiles. NEMBASE also
      features an interactive Java-based tool (SimiTri) which allows the simultaneous
      display and analysis of the relative similarity relationships of groups of
      sequences to three different databases. NEMBASE is currently being expanded to
      include sequence data from other nematode species. Other developments include
      access to accurate peptide predictions, improved functional annotation and
      incorporation of automated processes allowing rapid analysis of nematode-specific
      gene families.

PMID- 14681450
TI  - BRENDA, the enzyme database: updates and major new developments.
AB  - BRENDA (BRaunschweig ENzyme DAtabase) represents a comprehensive collection of
      enzyme and metabolic information, based on primary literature. The database
      contains data from at least 83,000 different enzymes from 9800 different
      organisms, classified in approximately 4200 EC numbers. BRENDA includes
      biochemical and molecular information on classification and nomenclature,
      reaction and specificity, functional parameters, occurrence, enzyme structure,
      application, engineering, stability, disease, isolation and preparation, links
      and literature references. The data are extracted and evaluated from
      approximately 46,000 references, which are linked to PubMed as long as the
      reference is cited in PubMed. In the past year BRENDA has undergone major changes
      including a large increase in updating speed with >50% of all data updated in
      2002 or in the first half of 2003, the development of a new EC-tree browser, a
      taxonomy-tree browser, a chemical substructure search engine for ligand
      structure, the development of controlled vocabulary, an ontology for some
      information fields and a thesaurus for ligand names. The database is accessible
      free of charge to the academic community at http://www.brenda. uni-koeln.de.

PMID- 14681451
TI  - IntEnz, the integrated relational enzyme database.
AB  - IntEnz is the name for the Integrated relational Enzyme database and is the
      official version of the Enzyme Nomenclature. The Enzyme Nomenclature comprises
      recommendations of the Nomenclature Committee of the International Union of Bio
      chemistry and Molecular Biology (NC-IUBMB) on the nomenclature and classification
      of enzyme-catalysed reactions. IntEnz is supported by NC-IUBMB and contains
      enzyme data curated and approved by this committee. The database IntEnz is
      available at http://www.ebi.ac.uk/intenz.

PMID- 14681452
TI  - MetaCyc: a multiorganism database of metabolic pathways and enzymes.
AB  - The MetaCyc database (see URL http://MetaCyc.org) is a collection of metabolic
      pathways and enzymes from a wide variety of organisms, primarily microorganisms
      and plants. The goal of MetaCyc is to contain a representative sample of each
      experimentally elucidated pathway, and thereby to catalog the universe of
      metabolism. MetaCyc also describes reactions, chemical compounds and genes. Many
      of the pathways and enzymes in MetaCyc contain extensive information, including
      comments and literature citations. SRI's Pathway Tools software supports
      querying, visualization and curation of MetaCyc. With its wide breadth and depth
      of metabolic information, MetaCyc is a valuable resource for a variety of
      applications. MetaCyc is the reference database of pathways and enzymes that is
      used in conjunction with SRI's metabolic pathway prediction program to create
      Pathway/Genome Databases that can be augmented with curation from the scientific
      literature and published on the world wide web. MetaCyc also serves as a readily
      accessible comprehensive resource on microbial and plant pathways for genome
      analysis, basic research, education, metabolic engineering and systems biology.
      In the past 2 years the data content and the Pathway Tools software used to
      query, visualize and edit MetaCyc have been expanded significantly. These
      enhancements are described in this paper.

PMID- 14681453
TI  - The aMAZE LightBench: a web interface to a relational database of cellular
      processes.
AB  - The aMAZE LightBench (http://www.amaze.ulb. ac.be/) is a web interface to the
      aMAZE relational database, which contains information on gene expression,
      catalysed chemical reactions, regulatory interactions, protein assembly, as well
      as metabolic and signal transduction pathways. It allows the user to browse the
      information in an intuitive way, which also reflects the underlying data model.
      Moreover links are provided to literature references, and whenever appropriate,
      to external databases.

PMID- 14681454
TI  - The Database of Interacting Proteins: 2004 update.
AB  - The Database of Interacting Proteins (http://dip.doe-mbi.ucla.edu) aims to
      integrate the diverse body of experimental evidence on protein-protein
      interactions into a single, easily accessible online database. Because the
      reliability of experimental evidence varies widely, methods of quality assessment
      have been developed and utilized to identify the most reliable subset of the
      interactions. This CORE set can be used as a reference when evaluating the
      reliability of high-throughput protein-protein interaction data sets, for
      development of prediction methods, as well as in the studies of the properties of
      protein interaction networks.

PMID- 14681455
TI  - IntAct: an open source molecular interaction database.
AB  - IntAct provides an open source database and toolkit for the storage, presentation
      and analysis of protein interactions. The web interface provides both textual and
      graphical representations of protein interactions, and allows exploring
      interaction networks in the context of the GO annotations of the interacting
      proteins. A web service allows direct computational access to retrieve
      interaction networks in XML format. IntAct currently contains approximately 2200
      binary and complex interactions imported from the literature and curated in
      collaboration with the Swiss-Prot team, making intensive use of controlled
      vocabularies to ensure data consistency. All IntAct software, data and controlled
      vocabularies are available at http://www.ebi.ac.uk/intact.

PMID- 14681456
TI  - STCDB: Signal Transduction Classification Database.
AB  - The Signal Transduction Classification Database (STCDB) is a database of
      information relative to the classification of signal transduction. It is based
      primarily on a proposed classification of signal transduction and it describes
      each type of characterized signal transduction for which a unique ST number has
      been provided. This document presents, in its first version, the classification
      of signal transduction in eukaryotic cells. Approved classifications are
      available for web browsing at http://www.techfak.uni-bielefeld.de/~ mchen/STCDB.

PMID- 14681457
TI  - MitoP2, an integrated database on mitochondrial proteins in yeast and man.
AB  - The aim of the MitoP2 database (http://ihg.gsf.de/mitop2) is to provide a
      comprehensive list of mitochondrial proteins of yeast and man. Based on the
      current literature we created an annotated reference set of yeast and human
      proteins. In addition, data sets relevant to the study of the mitochondrial
      proteome are integrated and accessible via search tools and links. They include
      computational predictions of signalling sequences, and summarize results from
      proteome mapping, mutant screening, expression profiling, protein-protein
      interaction and cellular sublocalization studies. For each individual approach,
      specificity and sensitivity for allocating mitochondrial proteins was calculated.
      By providing the evidence for mitochondrial candidate proteins the MitoP2
      database lends itself to the genetic characterization of human
      mitochondriopathies.

PMID- 14681458
TI  - MitoProteome: mitochondrial protein sequence database and annotation system.
AB  - MitoProteome is an object-relational mitochondrial protein sequence database and
      annotation system. The initial release contains 847 human mitochondrial protein
      sequences, derived from public sequence databases and mass spectrometric analysis
      of highly purified human heart mitochondria. Each sequence is manually annotated
      with primary function, subfunction and subcellular location, and extensively
      annotated in an automated process with data extracted from external databases,
      including gene information from LocusLink and Ensembl; disease information from
      OMIM; protein-protein interaction data from MINT and DIP; functional domain
      information from Pfam; protein fingerprints from PRINTS; protein family and
      family-specific signatures from InterPro; structure data from PDB; mutation data
      from PMD; BLAST homology data from NCBI NR; and proteins found to be related
      based on LocusLink and SWISS-PROT references and sequence and taxonomy data. By
      highly automating the processes of maintaining the MitoProteome Protein List and
      extracting relevant data from external databases, we are able to present a
      dynamic database, updated frequently to reflect changes in public resources. The
      MitoProteome database is publicly available at http://www. mitoproteome.org/.
      Users may browse and search MitoProteome, and access a complete compilation of
      data relevant to each protein of interest, cross-linked to external databases.

PMID- 14681459
TI  - Ensembl 2004.
AB  - The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics
      framework to organize biology around the sequences of large genomes. It is a
      comprehensive and integrated source of annotation of large genome sequences,
      available via interactive website, web services or flat files. As well as being
      one of the leading sources of genome annotation, Ensembl is an open source
      software engineering project to develop a portable system able to handle very
      large genomes and associated requirements. The facilities of the system range
      from sequence analysis to data storage and visualization and installations exist
      around the world both in companies and at academic sites. With a total of nine
      genome sequences available from Ensembl and more genomes to follow, recent
      developments have focused mainly on closer integration between genomes and
      external data.

PMID- 14681460
TI  - FREP: a database of functional repeats in mouse cDNAs.
AB  - The FREP database (http://facts.gsc.riken.go.jp/FREP/) contains 31 396
      RepeatMasker-identified non-redundant variant repeat sequences derived from
      16,527 mouse cDNAs with protein-coding potential. The repeats were
      computationally associated with potential effects on transcriptional variation,
      translation, protein function or involvement in disease to identify Functional
      REPeats (FREPs). FREPs are defined by the (i) occurrence of exon-exon boundaries
      in repeats, (ii) presence of polyadenylation sites in 3'UTR-located repeats,
      (iii) effect on translation, (iv) position in the protein- coding region or
      protein domains or (v) conditional association with disease MeSH terms. Currently
      the database contains 9261 (29.5%) inferred FREPs derived from 6861 (41.5%) mouse
      cDNAs. Integrated evidence of the functional assignments and dynamically
      generated sequence similarity search results support the exploration and
      annotation of functional, ancestral or taxon-specific repeats. Keyword and pre
      selected feature searches (e.g. coding sequence-repeat or splice site-repeat
      relations) support intuitive database querying as well as the retrieval of repeat
      sequences. Integrated sequence search and alignment tools allow the analysis of
      known or identification of new functional repeat candidates. FREP is a unique
      resource for illuminating the role of transposons and repetitive sequences in
      shaping the coding part of the mouse transcriptome and for selecting the
      appropriate experimental model to study diseases with suspected repeat etiology
      contributions.

PMID- 14681461
TI  - The Mouse Genome Database (MGD): integrating biology with the genome.
AB  - The Mouse Genome Database (MGD) is one component of the Mouse Genome Informatics
      (MGI) system (http://www.informatics.jax.org), a community database resource for
      the laboratory mouse. MGD strives to provide a comprehensive knowledgebase about
      the mouse with experiments and data annotated from both literature and online
      sources. MGD curates and presents consensus and experimental data representations
      of genetic, genotype (sequence) and phenotype information including highly
      detailed reports about genes and gene products. Primary foci of integration are
      through representations of relationships between genes, sequences and phenotypes.
      MGD collaborates with other bioinformatics groups to curate a definitive set of
      information about the laboratory mouse and to build and implement the data and
      semantic standards that are essential for comparative genome analysis. Recent
      developments in MGD discussed here include an extensive integration of the mouse
      sequence data and substantial revisions in the presentation, query and
      visualization of sequence data.

PMID- 14681462
TI  - The Mouse SAGE Site: database of public mouse SAGE libraries.
AB  - The Mouse SAGE Site is a web-based database of all available public libraries
      generated by the Serial Analysis of Gene Expression (SAGE) from various mouse
      tissues and cell lines. The database contains mouse SAGE libraries organized in a
      uniform way and provides web-based tools for browsing, comparing and searching
      SAGE data with reliable tag-to-gene identification. A modified approach based on
      the SAGEmap database is used for reliable tag identification. The Mouse SAGE Site
      is maintained on an ongoing basis at the Institute of Molecular Genetics, Academy
      of Sciences of the Czech Republic and is accessible at the internet address
      http://mouse.biomed.cas.cz/sage/.

PMID- 14681464
TI  - AluGene: a database of Alu elements incorporated within protein-coding genes.
AB  - Alu elements are short interspersed elements (SINEs) approximately 300
      nucleotides in length. More than 1 million Alus are found in the human genome.
      Despite their being genetically functionless, recent findings suggest that Alu
      elements may have a broad evolutionary impact by affecting gene structures,
      protein sequences, splicing motifs and expression patterns. Because of these
      effects, compiling a genomic database of Alu sequences that reside within protein
      coding genes seemed a useful enterprise. Presently, such data are limited since
      the structural and positional information on genes and Alu sequences are
      scattered throughout incompatible and unconnected databases. AluGene
      (http://Alugene.tau.ac.il/) provides easy access to a complete Alu map of the
      human genome, as well as Alu-associated information. The Alu elements are
      annotated with respect to coding region and exon/intron location. This design
      facilitates queries on Alu sequences, locations, as well as motifs and
      compositional properties via a one-stop search page.

PMID- 14681465
TI  - The UCSC Table Browser data retrieval tool.
AB  - The University of California Santa Cruz (UCSC) Table Browser
      (http://genome.ucsc.edu/cgi-bin/hgText) provides text-based access to a large
      collection of genome assemblies and annotation data stored in the Genome Browser
      Database. A flexible alternative to the graphical-based Genome Browser, this tool
      offers an enhanced level of query support that includes restrictions based on
      field values, free-form SQL queries and combined queries on multiple tables.
      Output can be filtered to restrict the fields and lines returned, and may be
      organized into one of several formats, including a simple tab- delimited file
      that can be loaded into a spreadsheet or database as well as advanced formats
      that may be uploaded into the Genome Browser as custom annotation tracks. The
      Table Browser User's Guide located on the UCSC website provides instructions and
      detailed examples for constructing queries and configuring output.

PMID- 14681466
TI  - Human protein reference database as a discovery resource for proteomics.
AB  - The rapid pace at which genomic and proteomic data is being generated
      necessitates the development of tools and resources for managing data that allow
      integration of information from disparate sources. The Human Protein Reference
      Database (http://www.hprd.org) is a web-based resource based on open source
      technologies for protein information about several aspects of human proteins
      including protein-protein interactions, post-translational modifications, enzyme
      substrate relationships and disease associations. This information was derived
      manually by a critical reading of the published literature by expert biologists
      and through bioinformatics analyses of the protein sequence. This database will
      assist in biomedical discoveries by serving as a resource of genomic and
      proteomic information and providing an integrated view of sequence, structure,
      function and protein networks in health and disease.

PMID- 14681467
TI  - HUGE: a database for human KIAA proteins, a 2004 update integrating HUGEppi and
      ROUGE.
AB  - We have been developing a Human Unidentified Gene-Encoded (HUGE) protein database
      (http://www.kazusa.or.jp/huge) to summarize results from sequence analysis of
      human novel large (>4 kb) cDNAs identified in the Kazusa cDNA sequencing project.
      At present, HUGE contains 2031 cDNA entries (KIAA cDNAs), for each of which a
      gene/protein characteristic table has been prepared. Since we have been shifting
      our research attention from the identification and cloning of novel cDNAs to the
      functional analysis of the proteins encoded by these cDNAs (KIAA proteins), we
      have not substantially increased the number of cDNA entries in HUGE for some
      time. Instead, we have manually curated 451 KIAA cDNAs in order to prepare a set
      of genetic resources to facilitate the functional analysis of KIAA proteins. In
      addition, we have updated the contents of the corresponding gene/protein
      characteristic tables in HUGE and have constructed two subsidiary databases,
      HUGEppi (http://www. kazusa.or.jp/huge/ppi) and ROUGE (http://www.
      kazusa.or.jp/rouge), to make available the results from our study of KIAA protein
      function. HUGEppi shows detailed information on protein-protein interactions
      detected between 84 pairs of KIAA proteins by yeast two-hybrid screening. ROUGE
      summarizes the results of computer-assisted analyses of approximately 1000 mouse
      homologues of human large cDNAs that we identified.

PMID- 14681463
TI  - PEDE (Pig EST Data Explorer): construction of a database for ESTs derived from
      porcine full-length cDNA libraries.
AB  - We generated the PEDE (Pig EST Data Explorer; http://pede.dna.affrc.go.jp/)
      database using sequences assembled from porcine 5' ESTs from oligo-capped full
      length cDNA libraries. Thus far we have performed EST analysis of various organs
      (thymus, spleen, uterus, lung, liver, ovary and peripheral blood mononuclear
      cells) and assembled 68,076 high-quality sequences into 5546 contigs and 28,461
      singlets. PEDE provides a search interface for getting results of homology
      searches and enables users to obtain information on sequence data and cDNA clones
      of interest. Single-nucleotide polymorphisms detected through comparison of the
      EST sequences are classified by origin (western and oriental breeds) and are
      searchable in the database. This database system can accelerate analyses of
      livestock traits and yields information that can lead to new applications in pigs
      as model systems for medical research.

PMID- 14681468
TI  - LIFEdb: a database for functional genomics experiments integrating information
      from external sources, and serving as a sample tracking system.
AB  - We have implemented LIFEdb (http://www.dkfz.de/LIFEdb) to link information
      regarding novel human full-length cDNAs generated and sequenced by the German
      cDNA Consortium with functional information on the encoded proteins produced in
      functional genomics and proteomics approaches. The database also serves as a
      sample-tracking system to manage the process from cDNA to experimental read-out
      and data interpretation. A web interface enables the scientific community to
      explore and visualize features of the annotated cDNAs and ORFs combined with
      experimental results, and thus helps to unravel new features of proteins with as
      yet unknown functions.

PMID- 14681469
TI  - trome, trEST and trGEN: databases of predicted protein sequences.
AB  - We previously introduced two new protein databases (trEST and trGEN) of
      hypothetical protein sequences predicted from EST and HTG sequences,
      respectively. Here, we present the updates made on these two databases plus a new
      database (trome), which uses alignments of EST data to HTG or full genomes to
      generate virtual transcripts and coding sequences. This new database is of higher
      quality and since it contains the information in a much denser format it is of
      much smaller size. These new databases are in a Swiss-Prot-like format and are
      updated on a weekly basis (trEST and trGEN) or every 3 months (trome). They can
      be downloaded by anonymous ftp from ftp://ftp.isrec.isb-sib.ch/pub/databases.

PMID- 14681470
TI  - Pathbase: a database of mutant mouse pathology.
AB  - Pathbase is a database that stores images of the abnormal histology associated
      with spontaneous and induced mutations of both embryonic and adult mice including
      those produced by transgenesis, targeted mutagenesis and chemical mutagenesis.
      Images of normal mouse histology and strain-dependent background lesions are also
      available. The database and the images are publicly accessible
      (http://www.pathbase.net) and linked by anatomical site, gene and other
      identifiers to relevant databases; there are also facilities for public comment
      and record annotation. The database is structured around a novel ontology of
      mouse disorders (MPATH) and provides high-resolution downloadable images of
      normal and diseased tissues that are searchable through orthogonal ontologies for
      pathology, developmental stage, anatomy and gene attributes (GO terms), together
      with controlled vocabularies for type of genetic manipulation or mutation,
      genotype and free text annotation for mouse strain and additional attributes. The
      database is actively curated and data records assessed by pathologists in the
      Pathbase Consortium before publication. The database interface is designed to
      have optimal browser and platform compatibility and to interact directly with
      other web-based mouse genetic resources.

PMID- 14681471
TI  - HGVbase: a curated resource describing human DNA variation and phenotype
      relationships.
AB  - The Human Genome Variation Database (HGVbase; http://hgvbase.cgb.ki.se) has
      provided a curated summary of human DNA variation for more than 5 years, thus
      facilitating research into DNA sequence variation and human phenotypes. The
      database has undergone many changes and improvements to accommodate increasing
      volumes and new types of data. The focus of HGVbase has recently shifted towards
      information on haplotypes and phenotypes, relationships between phenotypes and
      DNA variation, and collaborative efforts to provide a global resource for genome
      phenome data. Open sharing and precise phenotype definitions are necessary to
      advance the current understanding of common diseases that are typified by complex
      aetiologies, small genetic effect sizes and multiple confounding factors that
      obscure positive study results. Association data will increasingly be collected
      as part of this new project thrust. This report describes the evolving features
      of HGVbase, and covers in detail the technological choices we have made to enable
      efficient storage and data mining of increasingly large and complex data sets.

PMID- 14681472
TI  - topoSNP: a topographic database of non-synonymous single nucleotide polymorphisms
      with and without known disease association.
AB  - The database of topographic mapping of Single Nucleotide Polymorphism (topoSNP)
      provides an online resource for analyzing non-synonymous SNPs (nsSNPs) that can
      be mapped onto known 3D structures of proteins. These include disease- associated
      nsSNPs derived from the Online Mendelian Inheritance in Man (OMIM) database and
      other nsSNPs derived from dbSNP, a resource at the National Center for
      Biotechnology Information that catalogs SNPs. TopoSNP further classifies each
      nsSNP site into three categories based on their geometric location: those located
      in a surface pocket or an interior void of the protein, those on a convex region
      or a shallow depressed region, and those that are completely buried in the
      interior of the protein structure. These unique geometric descriptions provide
      more detailed mapping of nsSNPs to protein structures. The current release also
      includes relative entropy of SNPs calculated from multiple sequence alignment as
      obtained from the Pfam database (a database of protein families and conserved
      protein motifs) as well as manually adjusted multiple alignments obtained from
      ClustalW. These structural and conservational data can be useful for studying
      whether nsSNPs in coding regions are likely to lead to phenotypic changes.
      TopoSNP includes an interactive structural visualization web interface, as well
      as downloadable batch data. The database will be updated at regular intervals and
      can be accessed at: http://gila.bioengr.uic.edu/snp/toposnp.

PMID- 14681473
TI  - RTCGD: retroviral tagged cancer gene database.
AB  - Retroviral insertional mutagenesis in mouse hematopoietic tumors provides a
      potent cancer gene discovery tool in the post-genome-sequence era. To manage
      multiple high-throughput insertional mutagenesis screening projects, we developed
      the Retroviral Tagged Cancer Gene Database (RTCGD; http://RTCGD.ncifcrf.gov). A
      sequence analysis pipeline determines the genomic position of each retroviral
      integration site cloned from a mouse tumor, the distance between it and the
      nearest candidate disease gene(s) and its orientation with respect to the
      candidate gene(s). The pipeline also identifies genomic regions that are targets
      of retroviral integration in more than one tumor (common integration sites, CISs)
      and are thus likely to encode a disease gene. Users can search the database using
      a specified gene symbol, chromosome number or tumor model to identify both CIS
      genes and unique viral integration sites or compare the integration sites cloned
      by different laboratories using different models. As a default setting, users
      first review the CIS Lists and then Clone Lists. CIS Lists describe CISs and
      their candidate disease genes along with links to other public databases and
      clone lists. Clone Lists describe the viral integration site clones along with
      the tumor model and tumor type from which they were cloned, candidate disease
      gene(s), genomic position and orientation of the integrated provirus with respect
      to the candidate gene(s). It also provides a pictorial view of the genomic
      location of each integration site relative to neighboring genes and markers.
      Researchers can identify integrations of interest and compare their results with
      those for multiple tumor models and tumor types using RTCGD.

PMID- 14681474
TI  - SNP500Cancer: a public resource for sequence validation and assay development for
      genetic variation in candidate genes.
AB  - The SNP500Cancer Database provides sequence and genotype assay information for
      candidate single nucleotide polymorphisms (SNPs) useful in mapping complex
      diseases, such as cancer. The database is an integral component of the NCI's
      Cancer Genome Anatomy Project. SNP500Cancer provides bi-directional sequencing
      information on a set of control DNA samples derived from anonymized subjects (102
      Coriell samples representing four self-described ethnic groups: African/African
      American, Caucasian, Hispanic and Pacific Rim). All SNPs are chosen from public
      databases and reports, and the choice of genes includes a bias towards non
      synonymous and promoter SNPs in genes that have been implicated in one or more
      cancers. The web site is searchable by gene, chromosome, gene ontology pathway
      and by known dbSNP ID. As of July 2003, the database contains over 3400 SNPs,
      2490 of which have been sequenced in the SNP500Cancer population. For each
      analyzed SNP, gene location and over 200 bp of surrounding annotated sequence
      (including nearby SNPs) are provided, with frequency information in total and per
      subpopulation, and calculation of Hardy-Weinberg Equilibrium (HWE) for each
      subpopulation. Sequence validated SNPs with minor allele frequency > 5% are
      entered into a high-throughput pipeline for genotyping analysis to determine
      concordance for the same 102 samples. The website provides the conditions for
      validated genotyping assays. SNP500Cancer provides an invaluable resource for
      investigators to select SNPs for analysis, design genotyping assays using
      validated sequence data, choose selected assays already validated on one or more
      genotyping platforms, and select reference standards for genotyping assays. The
      SNP500Cancer Database is freely accessible via the web page at
      http://snp500cancer.nci.nih.gov/.

PMID- 14681475
TI  - ERGDB: Estrogen Responsive Genes Database.
AB  - ERGDB is an integrated knowledge database dedicated to genes responsive to
      estrogen. Genes included in ERGDB are those whose expression levels are
      experimentally proven to be either up-regulated or down-regulated by estrogen.
      Genes included are identified based on publications from the PubMed database and
      each record has been manually examined, evaluated and selected for inclusion by
      biologists. ERGDB aims to be a unified gateway to store, search, retrieve and
      update information about estrogen responsive genes. Each record contains links to
      relevant databases, such as GenBank, LocusLink, Refseq, PubMed and ATCC. The
      unique feature of ERGDB is that it contains information on the dependence of gene
      reactions on experimental conditions. In addition to basic information about the
      genes, information for each record includes gene functional description,
      experimental methods used, tissue or cell type, gene reaction, estrogen exposure
      time and the summary of putative estrogen response elements if the gene's
      promoter sequence was available. Through a web interface at http://sdmc.i2r.a
      star.edu.sg/ergdb/ cgi-bin/explore.pl users can either browse or query ERGDB.
      Access is free for academic and non-profit users.

PMID- 14681476
TI  - Improvements in the HbVar database of human hemoglobin variants and thalassemia
      mutations for population and sequence variation studies.
AB  - HbVar (http://globin.cse.psu.edu/globin/hbvar/) is a relational database
      developed by a multi-center academic effort to provide up-to-date and high
      quality information on the genomic sequence changes leading to hemoglobin
      variants and all types of thalassemia and hemoglobinopathies. Extensive
      information is recorded for each variant and mutation, including sequence
      alterations, biochemical and hematological effects, associated pathology, ethnic
      occurrence and references. In addition to the regular updates to entries, we
      report two significant advances: (i) The frequencies for a large number of
      mutations causing beta-thalassemia in at-risk populations have been extracted
      from the published literature and made available for the user to query upon. (ii)
      HbVar has been linked with the GALA (Genome Alignment and Annotation database,
      available at http://globin.cse.psu.edu/gala/) so that users can combine
      information on hemoglobin variants and thalassemia mutations with a wide spectrum
      of genomic data. It also expands the capacity to view and analyze the data, using
      tools within GALA and the University of California at Santa Cruz (UCSC) Genome
      Browser.

PMID- 14681477
TI  - CleanEx: a database of heterogeneous gene expression data based on a consistent
      gene nomenclature.
AB  - The main goal of CleanEx is to provide access to public gene expression data via
      unique gene names. A second objective is to represent heterogeneous expression
      data produced by different technologies in a way that facilitates joint analysis
      and cross-data set comparisons. A consistent and up-to-date gene nomenclature is
      achieved by associating each single experiment with a permanent target identifier
      consisting of a physical description of the targeted RNA population or the
      hybridization reagent used. These targets are then mapped at regular intervals to
      the growing and evolving catalogues of human genes and genes from model
      organisms. The completely automatic mapping procedure relies partly on external
      genome information resources such as UniGene and RefSeq. The central part of
      CleanEx is a weekly built gene index containing cross-references to all public
      expression data already incorporated into the system. In addition, the expression
      target database of CleanEx provides gene mapping and quality control information
      for various types of experimental resource, such as cDNA clones or Affymetrix
      probe sets. The web-based query interfaces offer access to individual entries via
      text string searches or quantitative expression criteria. CleanEx is accessible
      at: http://www.cleanex.isb-sib.ch/.

PMID- 14681478
TI  - EICO (Expression-based Imprint Candidate Organizer): finding disease-related
      imprinted genes.
AB  - We have developed an integrated database that is specialized for the study of
      imprinted disease genes. The database contains novel candidate imprinted genes
      identified by the RIKEN full-length mouse cDNA microarray study, information on
      validated single nucleotide polymorphisms (SNPs) to confirm imprinting using
      reciprocal mouse crosses and the predicted physical position of imprinting
      related disease loci in the mouse and human genomes. It has two user-friendly
      search interfaces: the SNP-central view (MuSCAT: MoUse SNP CATalog) and the
      candidate gene-central view (CITE: Candidate Imprinted Transcripts by
      Expression). The database, EICO (Expression-based Imprint Candidate Organizer),
      can be accessed via the World Wide Web (http://fantom2.gsc.riken.jp/EICODB/) and
      the DAS client software. These data and interfaces facilitate understanding of
      the mechanism of imprinting in mammalian inherited traits.

PMID- 14681479
TI  - GenePaint.org: an atlas of gene expression patterns in the mouse embryo.
AB  - High-throughput instruments were recently developed to determine gene expression
      patterns on tissue sections by RNA in situ hybridization. The resulting images of
      gene expression patterns, chiefly of E14.5 mouse embryos, are accessible to the
      public at http://www.genepaint.org. This relational database is searchable for
      gene identifiers and RNA probe sequences. Moreover, patterns and intensity of
      expression in approximately 100 different embryonic tissues are annotated and can
      be searched using a standardized catalog of anatomical structures. A virtual
      microscope tool, the Zoom Image Server, was implemented in GenePaint.org and
      permits interactive zooming and panning across approximately 15,000 high
      resolution images.

PMID- 14681480
TI  - The Centre for Modeling Human Disease Gene Trap resource.
AB  - Gene trap mutagenesis of mouse embryonic stem cells generates random loss-of
      function mutations, which can be identified by a sequence tag and can often
      report the endogenous expression of the mutated gene. The Centre for Modeling
      Human Disease is performing expression- and sequence-based screens of gene trap
      insertions to generate new mouse mutations as a resource for the scientific
      community. The gene trap insertions are screened using multiplexed in vitro
      differentiation and induction assays, and sequence tags are generated to
      complement expression profiles. Researchers may search for insertions in genes
      expressed in target cell lineages, under specific in vitro conditions, or based
      upon sequence identity via an online searchable database
      (http://www.cmhd.ca/sub/genetrap.asp). The clones are available as a resource to
      researchers worldwide to help to functionally annotate the mammalian genome and
      will serve as a source to test candidate loci identified by phenotype-driven
      mutagenesis screens.

PMID- 14681481
TI  - GermOnline, a cross-species community knowledgebase on germ cell differentiation.
AB  - GermOnline provides information and microarray expression data for genes involved
      in mitosis and meiosis, gamete formation and germ line development across
      species. The database has been developed, and is being curated and updated, by
      life scientists in cooperation with bioinformaticists. Information is contributed
      through an online form using free text, images and the controlled vocabulary
      developed by the GeneOntology Consortium. Authors provide up to three references
      in support of their contribution. The database is governed by an international
      board of scientists to ensure a standardized data format and the highest quality
      of GermOnline's information content. Release 2.0 provides exclusive access to
      microarray expression data from Saccharomyces cerevisiae and Rattus norvegicus,
      as well as curated information on approximately 700 genes from various organisms.
      The locus report pages include links to external databases that contain relevant
      annotation, microarray expression and proteome data. Conversely, the
      Saccharomyces Genome Database (SGD), S.cerevisiae GeneDB and Swiss-Prot link to
      the budding yeast section of GermOnline from their respective locus pages.
      GermOnline, a fully operational prototype subject-oriented knowledgebase designed
      for community annotation and array data visualization, is accessible at
      http://www.germonline.org. The target audience includes researchers who work on
      mitotic cell division, meiosis, gametogenesis, germ line development, human
      reproductive health and comparative genomics.

PMID- 14681482
TI  - The mouse Gene Expression Database (GXD): updates and enhancements.
AB  - The Gene Expression Database (GXD) is a community resource for gene expression
      information in the laboratory mouse. By collecting and integrating different
      types of expression data, GXD provides information about expression profiles in
      different mouse strains and mutants. Participation in the Gene Ontology (GO)
      project classifies genes and gene products with regard to molecular functions,
      biological processes, and cellular components. Integration with other Mouse
      Genome Informatics (MGI) databases places the gene expression information in the
      context of mouse genetic, genomic and phenotypic information. The integration of
      these types of information enables valuable insights into the molecular biology
      that underlies development and disease. The utility of GXD has been improved by
      the daily addition of new data and through the implementation of new query and
      display features. These improvements make it easier for users to interrogate and
      visualize expression data in the context of their specific needs. GXD is
      accessible through the MGI website at http://www.informatics.jax.org/ or directly
      at http://www. informatics.jax.org/menus/expression_menu.shtml.

PMID- 14681483
TI  - Hembase: browser and genome portal for hematology and erythroid biology.
AB  - Hembase (http://hembase.niddk.nih.gov) is an integrated browser and genome portal
      designed for web-based examination of the human erythroid transcriptome. To date,
      Hembase contains 15,752 entries from erythroblast Expressed Sequenced Tags (ESTs)
      and 380 referenced genes relevant for erythropoiesis. The database is organized
      to provide a cytogenetic band position, a unique name as well as a concise
      annotation for each entry. Search queries may be performed by name, keyword or
      cytogenetic location. Search results are linked to primary sequence data and
      three major human genome browsers for access to information considered current at
      the time of each search. Hembase provides interested scientists and clinical
      hematologists with a genome-based approach toward the study of erythroid biology.

PMID- 14681484
TI  - NASCArrays: a repository for microarray data generated by NASC's transcriptomics
      service.
AB  - NASC operates an Affymetrix 'GeneChip' (microarray) service for the Arabidopsis
      thaliana community. All data produced by the service are publicly available
      through our microarray data base 'NASCArrays' published at http://affymetrix.
      arabidopsis.info. The data are accessible through text searching and a series of
      data mining tools. All data are annotated with sample preparation details, and
      the original Affymetrix data are available for download. The database aims to be
      MIAME supportive and provide a coordinated resource for re searchers interested
      in the transcriptome of Arabidopsis. Using this database, data produced will be
      shared with other databases worldwide.

PMID- 14681485
TI  - The PEPR GeneChip data warehouse, and implementation of a dynamic time series
      query tool (SGQT) with graphical interface.
AB  - Publicly accessible DNA databases (genome browsers) are rapidly accelerating post
      genomic research (see http://www.genome.ucsc.edu/), with integrated genomic DNA,
      gene structure, EST/ splicing and cross-species ortholog data. DNA databases have
      relatively low dimensionality; the genome is a linear code that anchors all
      associated data. In contrast, RNA expression and protein databases need to be
      able to handle very high dimensional data, with time, tissue, cell type and
      genes, as interrelated variables. The high dimensionality of microarray
      expression profile data, and the lack of a standard experimental platform have
      complicated the development of web-accessible databases and analytical tools. We
      have designed and implemented a public resource of expression profile data
      containing 1024 human, mouse and rat Affymetrix GeneChip expression profiles,
      generated in the same laboratory, and subject to the same quality and procedural
      controls (Public Expression Profiling Resource; PEPR). Our Oracle-based PEPR data
      warehouse includes a novel time series query analysis tool (SGQT), enabling
      dynamic generation of graphs and spreadsheets showing the action of any
      transcript of interest over time. In this report, we demonstrate the utility of
      this tool using a 27 time point, in vivo muscle regeneration series. This data
      warehouse and associated analysis tools provides access to multidimensional
      microarray data through web-based interfaces, both for download of all types of
      raw data for independent analysis, and also for straightforward gene-based
      queries. Planned implementations of PEPR will include web-based remote entry of
      projects adhering to quality control and standard operating procedure (QC/SOP)
      criteria, and automated output of alternative probe set algorithms for each
      project (see http://microarray.cnmcresearch.org/pgadatatable.asp).

PMID- 14681486
TI  - GELBANK: a database of annotated two-dimensional gel electrophoresis patterns of
      biological systems with completed genomes.
AB  - GELBANK is a publicly available database of two-dimensional gel electrophoresis
      (2DE) gel patterns of proteomes from organisms with known genome information
      (available at http://gelbank.anl.gov and ftp://bioinformatics.anl.gov/gelbank/).
      Currently it includes 131 completed, mostly microbial proteomes available from
      the National Center for Biotechnology Information. A web interface allows the
      upload of 2D gel patterns and their annotation for registered users. The images
      are organized by species, tissue type, separation method, sample type and
      staining method. The database can be queried based on protein or 2DE-pattern
      attributes. A web interface allows registered users to assign molecular weight
      and pH gradient profiles to their own 2D gel patterns as well as to link protein
      identifications to a given spot on the pattern. The website presents all of the
      submitted 2D gel patterns where the end-user can dynamically display the images
      or parts of images along with molecular weight, pH profile information and linked
      protein identification. A collection of images can be selected for the creation
      of animations from which the user can select sub-regions of interest and
      unlimited 2D gel patterns for visualization. The website currently presents 233
      identifications for 81 gel patterns for Homo sapiens, Methanococcus jannaschii,
      Pyro coccus furiosus, Shewanella oneidensis, Escherichia coli and Deinococcus
      radiodurans.

PMID- 14681487
TI  - ANTIMIC: a database of antimicrobial sequences.
AB  - Antimicrobial peptides (AMPs) are important components of the innate immune
      system of many species. These peptides are found in eukaryotes, including
      mammals, amphibians, insects and plants, as well as in prokaryotes. Other than
      having pathogen-lytic properties, these peptides have other activities like
      antitumor activity, mitogen activity, or they may act as signaling molecules.
      Their short length, fast and efficient action against microbes and low toxicity
      to mammals have made them potential candidates as peptide drugs. In many cases
      they are effective against pathogens that are resistant to conventional
      antibiotics. They can serve as natural templates for the design of novel
      antimicrobial drugs. Although there are vast amounts of data on natural AMPs,
      they are not available through one central resource. We have developed a
      comprehensive database (ANTIMIC, http://research.i2r. a
      star.edu.sg/Templar/DB/ANTIMIC/) of known and putative AMPs, which contains
      approximately 1700 of these peptides. The database is integrated with tools to
      facilitate efficient extraction of data and their analysis at molecular level, as
      well as search for new AMPs. These tools include BLAST, PDB structure viewer and
      the Antimic profile module.

PMID- 14681488
TI  - APD: the Antimicrobial Peptide Database.
AB  - An antimicrobial peptide database (APD) has been established based on an
      extensive literature search. It contains detailed information for 525 peptides
      (498 antibacterial, 155 antifungal, 28 antiviral and 18 antitumor). APD provides
      interactive interfaces for peptide query, prediction and design. It also provides
      statistical data for a select group of or all the peptides in the database.
      Peptide information can be searched using keywords such as peptide name, ID,
      length, net charge, hydrophobic percentage, key residue, unique sequence motif,
      structure and activity. APD is a useful tool for studying the structure-function
      relationship of antimicrobial peptides. The database can be accessed via a web
      based browser at the URL: http://aps.unmc.edu/AP/main.html.

PMID- 14681489
TI  - The Peptaibol Database: a database for sequences and structures of naturally
      occurring peptaibols.
AB  - The Peptaibol Database is a sequence and structure resource for the unusual class
      of peptides known as peptaibols. These peptides exhibit antibiotic and membrane
      channel-forming activities. The database includes sequence, biological source and
      bibliographical data for the naturally occurring peptaibols. Information is also
      collated for the growing number of peptaibol 3D structures determined by either
      crystallography or NMR spectroscopy. The database can be obtained as a whole or
      can be queried by name, group, sequence motif, biological origin and/or
      literature reference. The Peptaibol Database can be freely accessed at
      http://www.cryst.bbk.ac.uk/peptaibol.

PMID- 14681490
TI  - ORFDB: an information resource linking scientific content to a high-quality Open
      Reading Frame (ORF) collection.
AB  - The ORFDB (http://orf.invitrogen.com/) represents an ongoing effort at Invitrogen
      Corporation to integrate relevant scientific data with an evolving collection of
      human and mouse Open Reading Frame (ORF) clones (Ultimate ORF Clones). The ORFDB
      serves as a central data warehouse enabling researchers to search the ORF
      collection through its web portal ORFBrowser, allowing researchers to find the
      Ultimate ORF clones by blast, keyword, GenBank accession, gene symbol, clone ID,
      Unigene ID, LocusLink ID or through functional relationships by browsing the
      collection via the Gene Ontology (GO) Browser. As of October 2003, the ORFDB
      contains 6200 human and 2870 mouse Ultimate ORF clones. All Ultimate ORF clones
      have been fully sequenced with high quality, and are matched to public reference
      protein sequences. In addition, the cloned ORFs have been extensively annotated
      across six categories: Gene, ORF, Clone Format, Protein, SNP and Genomic links,
      with the information assembled in a format termed the ORFCard. The ORFCard
      represents an information repository that documents the sequence quality,
      alignment with respect to public protein sequences, and the latest publicly
      available information associated with each human and mouse gene represented in
      the collection.

PMID- 14681492
TI  - Repetitive hypoglycemia in young rats impairs hippocampal long-term potentiation.
AB  - Mechanisms underlying cognitive dysfunction in young diabetic children are poorly
      understood, and may include synaptic dysfunction from insulin-induced
      hypoglycemia. We developed a model of repetitive insulin-induced hypoglycemia in
      young rats and examined hippocampal long-term potentiation, an electrophysiologic
      assay of synaptic plasticity, 3-5 d after the last hypoglycemic event. Three
      hypoglycemic events between postnatal d 21-25 produced modest cortical (17 +/-
      2.9 dead neurons per section in parasagittal cortex), but not hippocampal, neuron
      death quantified by Fluoro-Jade B staining. There was no change in neurogenesis
      in the hippocampal dentate granule cell region by quantification of
      bromodeoxyuridine incorporation. Although normal baseline hippocampal synaptic
      responses were elicited from hippocampal slices from hypoglycemic animals, long
      term synaptic potentiation could not be induced in hippocampal slices from rats
      subjected to hypoglycemia. These results suggest that repetitive hypoglycemia in
      the developing brain can cause selective impairment of synaptic plasticity in the
      absence of cell death, and without complete disruption of basal synaptic
      transmission. We speculate that impaired synaptic plasticity in the hippocampus
      caused by repetitive hypoglycemia could underlie memory and cognitive deficits
      observed in young diabetic children, and that cortical neuron death caused by
      repetitive hypoglycemia in the developing brain may contribute to other
      neurologic, cognitive, and psychological problems sometimes encountered in
      diabetic children.

PMID- 14681491
TI  - Gastric function in children with cystic fibrosis: effect of diet on gastric
      lipase levels and fat digestion.
AB  - The effect of diet, usual (44 +/- 4% energy as fat), high-fat (49 +/- 4% energy
      as fat), and moderate-fat (33 +/- 2% energy as fat), on gastric function (lipase
      and pepsin activities, pH, emptying rate) and intragastric digestion of fat were
      assessed in six children with cystic fibrosis. Fasting and postprandial activity
      of digestive enzymes, gastric pH, and gastric volume measured before, during, and
      after 120 min of feeding did not differ significantly as a function of fat
      intake. Postprandial gastric lipase output (units per kilogram of body weight)
      during usual, moderate-fat, and high-fat diets was close to or higher than (38.8
      +/- 7.2, 44.9 +/- 8.6, and 54.8 +/- 5.5 U/kg per 20 min) gastric lipase output of
      premature infants (22.5 +/- 6.4 to 28.3 +/- 6.6 U/kg per 20 min) or of healthy
      adults (5.4 +/- 0.4 U/kg per 15 min) fed a high-fat diet. Postprandial pepsin
      output was higher (4749 +/- 797, 6117 +/- 925, and 5444 +/- 819 U/kg per 20 min)
      than in premature infants (597 +/- 77 to 743 +/- 97 U/kg per 20 min) or healthy
      adults (781 +/- 56 U/kg per 15 min). Eighty minutes after feeding gastric
      lipolysis reached 20 to 36%. This study shows that gastric lipase activity is
      high in cystic fibrosis patients maintained on diets providing 32% to 49% energy
      as fat, and that gastric lipase level did not increase over the ranges of dietary
      fat intake tested.

PMID- 14681493
TI  - Insulin-like growth factor-I governs submucosal growth and thickness in the
      newborn mouse ileum.
AB  - Spontaneous intestinal perforations in extremely premature infants are associated
      with glucocorticoid-induced thinning of the ileal bowel wall. We have previously
      demonstrated that insulin-like growth factor-1 (IGF-1) is abundant within the
      submucosa of the newborn mouse ileum but is diminished by glucocorticoid
      exposure, concomitant with bowel wall thinning. These findings prompted us to
      hypothesize that IGF-I governs submucosal growth during neonatal gut development
      and that diminished IGF-I abundance results in submucosal thinning. Heterozygous
      IGF-I knockout, wild type and homozygous IGF-I over-expresser newborn mice were
      euthanized at 3 d of life. Additionally, wild type newborn mice received daily
      dexamethasone (DEX) (1microg/gm/d) or vehicle control on days of life 1 and 2 and
      were also euthanized at 3 d of life. Their ileums were harvested, fixed and the
      resulting sections were processed in parallel for IGF-I immunohistochemistry and
      morphometric measurements of submucosal thickness and bowel diameter.
      Immunolocalization of IGF-I in each genotype was also compared with that seen in
      DEX-treated and control mice euthanized at the same time of life. IGF-I
      heterozygous knockouts had diminished submucosal IGF-I immunolocalization
      (similar to that seen in DEX-treated newborn mice) whereas homozygous IGF-I over
      expressers exceeded that seen within wild type mice. IGF-I genotype and
      submucosal abundance was positively correlated with ileal submucosal thickness.
      DEX treatment of newborn mice diminished IGF-I and caused significant thinning of
      the submucosa compared with controls. Submucosal growth and thickness in the
      neonatal mouse ileum is governed by IGF-I and is diminished by dexamethasone
      treatment.

PMID- 14681494
TI  - Regulation of muscle protein synthesis in neonatal pigs during prolonged
      endotoxemia.
AB  - In adults, protein synthesis in skeletal muscle is reduced by as much as 50%
      after a septic challenge, and is associated with repression of translation
      initiation. Neonates are highly anabolic and their muscle protein synthesis rates
      are elevated and uniquely sensitive to amino acid and insulin stimulation. In the
      present study, neonatal piglets were infused with Endotoxin (lipopolysaccharide,
      LPS) for 20 h at 0 (n = 6) and 13 microg/kg*h (n = 8). During the last 2 h,
      dextrose and an amino acid mixture were infused to attain fed plasma
      concentrations of amino acids, glucose, and insulin. Fractional protein synthesis
      rates and translational control mechanisms were examined. LPS reduced protein
      synthesis in glycolytic muscles by only 13% and had no significant effect in
      oxidative muscles. This depression was associated with reductions in the
      phosphorylation of 4E-BP1 (-31%) and S6 K1 (-78%), and a decrease in eIF4G
      binding to eIF4E (-62%), an event required for formation of the active mRNA
      binding complex. By comparison, LPS increased protein synthesis in the liver
      (+29%), spleen (+32%), and kidney (+27%), and in the liver, this increase was
      associated with augmented eIF4G to eIF4E binding (+88%). In muscle and liver, LPS
      did not alter eIF2B activity, an event that regulates initiator met-tRNA(i)
      binding to the 40S ribosomal complex. These findings suggest that during
      sustained endotoxemia, the high rate of neonatal muscle protein synthesis is
      largely maintained in the presence of substrate supply, despite profound changes
      in translation initiation factors that modulate the mRNA binding step in
      translation initiation.

PMID- 14681495
TI  - Glutathione S transferase theta 1 gene (GSTT1) null genotype is associated with
      an increased risk for acquired aplastic anemia in children.
AB  - Two main factors have been implicated in the mechanism underlying the
      pathogenesis of acquired aplastic anemia: environmental factors and genetic
      susceptibility. Individuals vary in their ability to metabolize several DNA
      damaging agents due to polymorphisms of biotransforming enzymes. Genetically
      determined differences in the expression of these enzymes could explain
      interindividual risks in developing acquired aplastic anemia. The aim of the
      study was to characterize the genetic polymorphism of biotransforming phase I
      (p450-cyp2E1) and phase II [microsomal epoxide hydrolase (mEh), glutathione S
      transferase (GST)] enzymes in pediatric patients with acquired aplastic anemia.
      The GSTT1 null genotype (absence of both alleles) was associated with a
      significantly increased risk for acquired aplastic anemia (odds ratio, 2.8; 95%
      confidence interval, 0.15-5.7). In contrast, the GSTM1 null genotype or
      polymorphisms within the p450-cyp2E1 and mEh genes was not significantly
      different in patients and controls. Multivariate analysis was performed to assess
      whether the enzymes together or with other variables as age, gender, or response
      to therapy may have any significant association with the tested genotypes. In no
      combinations of the mentioned parameters was an association found with acquired
      aplastic anemia. GST are mainly involved in metabolizing hematotoxic and
      mutagenic substrates such as benzene derivatives. The GSTT1 null genotype may
      modulate the metabolism of exogenous pollutants or toxic intermediates. The
      absence of the GSTT1 enzyme, leading to genetic susceptibility toward certain
      pollutants, might determine the individual risk for development of acquired
      aplastic anemia in children.

PMID- 14681496
TI  - Distribution of adipose tissue in the newborn.
AB  - Regional differences in adipose tissue distribution are associated with
      differences in adipocyte metabolism and obesity-related morbidities. Intrauterine
      growth restriction appears to place individuals at greater risk of obesity
      associated morbidities in later life. Despite this, little is known regarding the
      quantity and distribution of adipose tissue in infants during early development.
      The aim of this study was to compare total and regional adipose tissue content in
      appropriate-for-gestational-age (AGA) and growth-restricted (GR) newborn infants
      born at or near term. Whole body adipose tissue magnetic resonance imaging (MRI)
      was performed as soon as possible after birth. Total and regional adipose tissue
      depots were quantified. A total of 35 infants (10 GR; 25 AGA) were studied. Mean
      (SD) total percentage adipose tissue was lower in GR infants than AGA infants
      [GR: 17.70% (2.17); AGA: 23.40% (3.85); p = 0.003]. This difference arose from
      differences in subcutaneous adipose tissue mass [mean (SD) percentage
      subcutaneous adipose tissue mass, GR: 16.13% (2.20); AGA: 21.44% (3.81); p =
      0.004], but not intra-abdominal adipose tissue mass [mean (SD) percentage intra
      abdominal adipose tissue, GR: 0.42% (0.22); AGA: 0.61% (0.31); p = 0.45]. In
      contrast to subcutaneous adipose tissue, intra-abdominal adipose tissue is not
      reduced in infants with intrauterine growth restriction. This suggests that
      subcutaneous and intra-abdominal adipose tissue compartments may be under
      different regulatory control during intrauterine life.

PMID- 14681497
TI  - Transient hyperoxia and residual cerebrovascular effects in the newborn rat.
AB  - Unrestricted use of oxygen in the delivery room after preterm birth has been
      associated with reduced cerebral blood flow (CBF) 2 h later. To further
      investigate residual cerebrovascular effects of transient hyperoxia, we developed
      a newborn rat model in which laser-Doppler flowmetry (LDF) and near-infrared
      spectroscopy (NIRS) were used to monitor changes in cerebral perfusion. The
      hypothesis to be tested was that hyperoxic exposure limits cerebral vasodilation
      in response to increase in carbon dioxide tension (Pco(2)). Twenty-four 3- to 5-d
      old rats were kept on spontaneous breathing with doxapram under light isoflurane
      anesthesia, randomized into two groups, and exposed to either room air or 100%
      oxygen for 30 min. Then, after 15 min of stabilization in normoxia, 8% CO(2) was
      given for 5 min. No significant differences in CO(2) responses were observed
      between the two groups: mean CBF-CO(2) reactivity as measured by NIRS was 13.3 +/
      3.9 %/kPa in the normoxia-group versus 8.8 +/- 4.1 %/kPa in the hyperoxia group
      (NS). The oxygenation index [(HbO(2) - Hb)/2] increased by 0.67 +/- 0.17
      micromol/L/kPa in the normoxia group compared with 1.18 +/- 0.19 micromol/L/kPa
      in the hyperoxia group (NS). Cortical perfusion, monitored by LDF, increased by
      7.3 +/- 1.5 %/kPa versus 6.8 +/- 1.8 %/kPa in the normoxia and hyperoxia groups,
      respectively (NS). We conclude that in newborn rats the CBF-CO(2) reactivity
      remains intact after 30 min of oxygen exposure.

PMID- 14681498
TI  - Long-term treatment and diagnosis of tetrahydrobiopterin-responsive
      hyperphenylalaninemia with a mutant phenylalanine hydroxylase gene.
AB  - A novel therapeutic strategy for phenylketonuria (PKU) has been initiated in
      Japan. A total of 12 patients who met the criteria for tetrahydrobiopterin
      (BH(4))-responsive hyperphenylalaninemia (HPA) with a mutant phenylalanine
      hydroxylase (PAH) (EC 1.14.16.1) gene were recruited at 12 medical centers in
      Japan between June 1995 and July 2001. Therapeutic efficacy of BH(4) was
      evaluated in single-dose, four-dose, and 1-wk BH(4) loading tests followed by
      long-term BH(4) treatment, and also examined in relation to the PAH gene
      mutations. The endpoints were determined as the percentage decline in serum
      phenylalanine from initial values after single-dose (>20%), four-dose (>30%), and
      1-wk BH(4) (>50%) loading tests. Patients with mild PKU exhibiting decreases in
      blood phenylalanine concentrations of >20% in the single-dose test also
      demonstrated decreases of >30% in the four-dose test. The 1-wk test elicited
      BH(4) responsiveness even in patients with poor responses in the shorter tests.
      Patients with mild HPA, many of whom carry the R241C allele, responded to BH(4)
      administration. No clear correlation was noted between the degree of decrease in
      serum phenylalanine concentrations in the single- or four-dose tests and specific
      PAH mutations. The 1-wk test (20 mg/kg of BH(4) per day) is the most sensitive
      test for the diagnosis of BH(4)-responsive PAH deficiency. Responsiveness
      apparently depends on mutations in the PAH gene causing mild PKU, such as R241C.
      BH(4) proved to be an effective therapy that may be able to replace or liberalize
      the phenylalanine-restricted diets for a considerable number of patients with
      mild PKU.

PMID- 14681499
TI  - Cerebrovascular effects of rapid volume expansion in preterm fetal sheep.
AB  - Preterm human infants are often treated with volume expansion during their
      initial stabilization. There are limited data regarding the cerebral vascular
      effects of this therapeutic approach. The effects of blood volume expansion on
      cerebral vascular reactivity and oxygen metabolism in very immature animals have
      not been determined. We examined the effects of volume expansion, with and
      without hypoxia, on cerebral blood flow and metabolism in unanesthetized,
      chronically catheterized, preterm fetal sheep. Rapid volume expansion with i.v.
      dextran increased circulating blood volume. Arterial blood pressure did not
      increase, nor did cerebral blood flow. However, volume expansion resulted in
      lower arterial Hb concentration and, consequently, oxygen content without a
      compensatory increase in cerebral blood flow. Cerebral oxygen delivery fell
      significantly. Induction of severe hypoxia after volume expansion resulted in an
      increase in cerebral blood flow, as expected, but the increase in flow was not
      enough to maintain cerebral oxygen delivery. Rapid volume expansion in
      normovolemic preterm fetal sheep is associated with decreased cerebral oxygen
      delivery, and this is further compromised when oxygen content is decreased.

PMID- 14681500
TI  - Cerebral fractional oxygen extraction in very low birth weight infants is high
      when there is low left ventricular output and hypocarbia but is unaffected by
      hypotension.
AB  - This study examined the relationships between cerebral fractional oxygen
      extraction (FOE), mean arterial blood pressure (MABP), left ventricular output
      (LVO), blood gases, and other physiologic variables in 36 very-low-birth-weight
      preterm infants during the first 3 d after birth. There was a decrease in
      cerebral FOE (p = 0.008), and rises in LVO (p < 0.0001) and MABP (p = 0.02)
      during the 3 d. Between d 1 and 2, cerebral FOE decreased (p = 0.007) and LVO
      increased (p < 0.0001). There was no relationship between MABP and cerebral FOE.
      LVO correlated negatively with cerebral FOE on d 1 (p = 0.01), but not on d 2 (p
      = 0.07). On d 1, median pressure of arterial CO(2) was lower in infants with low
      LVO (<5(th) centile) and high cerebral FOE (>95(th) centile) than in infants with
      low LVO (<5(th) centile) but normal cerebral FOE (5(th)-95(th) centile) (p =
      0.03). These findings suggest that cerebral FOE was increased only when LVO was
      low and there was hypocarbia. MABP had no demonstrable effect. It is likely that
      increased cerebral FOE is a normal physiologic response to maintain an adequate
      oxygen supply to the cerebral tissues when LVO is low and hypocarbia has caused
      vasoconstriction. It is possible that the cerebral hemispheres are low-priority
      vascular beds in the preterm infant, and that the high cerebral FOE is a result
      of reduced hemispheric blood flow to maintain MABP in the presence of low LVO.

PMID- 14681501
TI  - Systemic lupus erythematosus and accelerated atherosclerosis.

PMID- 14681502
TI  - SARS--one year later.

PMID- 14681503
TI  - Dispatch from India.

PMID- 14681504
TI  - The long-term effect of doxazosin, finasteride, and combination therapy on the
      clinical progression of benign prostatic hyperplasia.
AB  - BACKGROUND: Benign prostatic hyperplasia is commonly treated with alpha
      adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors.
      The long-term effect of these drugs, singly or combined, on the risk of clinical
      progression is unknown. METHODS: We conducted a long-term, double-blind trial
      (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo,
      doxazosin, finasteride, and combination therapy on measures of the clinical
      progression of benign prostatic hyperplasia. RESULTS: The risk of overall
      clinical progression--defined as an increase above base line of at least 4 points
      in the American Urological Association symptom score, acute urinary retention,
      urinary incontinence, renal insufficiency, or recurrent urinary tract infection-
      was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and
      finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The
      reduction in risk associated with combination therapy (66 percent for the
      comparison with placebo, P<0.001) was significantly greater than that associated
      with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute
      urinary retention and the need for invasive therapy were significantly reduced by
      combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin.
      Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001)
      each resulted in significant improvement in symptom scores, with combination
      therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001)
      alone. CONCLUSIONS: Long-term combination therapy with doxazosin and finasteride
      was safe and reduced the risk of overall clinical progression of benign prostatic
      hyperplasia significantly more than did treatment with either drug alone.
      Combination therapy and finasteride alone reduced the long-term risk of acute
      urinary retention and the need for invasive therapy.

PMID- 14681505
TI  - Prevalence and correlates of accelerated atherosclerosis in systemic lupus
      erythematosus.
AB  - BACKGROUND: Although systemic lupus erythematosus is associated with premature
      myocardial infarction, the prevalence of underlying atherosclerosis and its
      relation to traditional risk factors for cardiovascular disease and lupus-related
      factors have not been examined in a case-control study. METHODS: In 197 patients
      with lupus and 197 matched controls, we performed carotid ultrasonography,
      echocardiography, and an assessment for risk factors for cardiovascular disease.
      The patients were also evaluated with respect to their clinical and serologic
      features, inflammatory mediators, and disease treatment. RESULTS: The risk
      factors for cardiovascular disease were similar among patients and controls.
      Atherosclerosis (carotid plaque) was more prevalent among patients than the
      controls (37.1 percent vs. 15.2 percent, P<0.001). In multivariate analysis, only
      older age, the presence of systemic lupus erythematosus (odds ratio, 4.8; 95
      percent confidence interval, 2.6 to 8.7), and a higher serum cholesterol level
      were independently related to the presence of plaque. As compared with patients
      without plaque, patients with plaque were older, had a longer duration of disease
      and more disease-related damage, and were less likely to have multiple
      autoantibodies or to have been treated with prednisone, cyclophosphamide, or
      hydroxychloroquine. In multivariate analyses including patients with lupus,
      independent predictors of plaque were a longer duration of disease, a higher
      damage-index score, a lower incidence of the use of cyclophosphamide, and the
      absence of anti-Smith antibodies. CONCLUSIONS: Atherosclerosis occurs prematurely
      in patients with systemic lupus erythematosus and is independent of traditional
      risk factors for cardiovascular disease. The clinical profile of patients with
      lupus and atherosclerosis suggests a role for disease-related factors in
      atherogenesis and underscores the need for trials of more focused and effective
      antiinflammatory therapy.

PMID- 14681506
TI  - Premature coronary-artery atherosclerosis in systemic lupus erythematosus.
AB  - BACKGROUND: Premature coronary artery disease is a major cause of illness and
      death in patients with systemic lupus erythematosus, but little is known about
      the prevalence, extent, and causes of coronary-artery atherosclerosis. METHODS:
      We used electron-beam computed tomography to screen for the presence of coronary
      artery calcification in 65 patients with systemic lupus erythematosus (mean [+/
      SD] age, 40.3+/-11.6 years) and 69 control subjects (mean age, 42.7+/-12.6 years)
      with no history of coronary artery disease. When calcification was detected, the
      extent was measured by means of the Agatston score. The frequency of risk factors
      for coronary artery disease was compared in patients and controls, and the
      relation between the patients' clinical characteristics and the presence or
      absence of coronary-artery calcification was examined. RESULTS: The two groups
      were similar with respect to age, race, and sex. Coronary-artery calcification
      was more frequent in patients with lupus (20 of 65 patients) than in control
      subjects (6 of 69 subjects) (P=0.002). The mean calcification score was 68.9+/
      244.2 in the patients and 8.8+/-41.8 (P<0.001) in controls. Levels of total, high
      density lipoprotein, and low-density lipoprotein cholesterol were not elevated in
      patients with lupus, but levels of triglycerides (P=0.02) and homocysteine
      (P<0.001) were. Among patients with lupus, measures of disease activity were
      similar in those with and those without coronary-artery calcification, but those
      with calcification were more likely to be older (P<0.001) and male (P=0.008).
      CONCLUSIONS: In patients with systemic lupus erythematosus, the prevalence of
      coronary-artery atherosclerosis is elevated and the age at onset is reduced.
      Early detection of atherosclerosis may provide an opportunity for therapeutic
      intervention.

PMID- 14681507
TI  - Transmission of the severe acute respiratory syndrome on aircraft.
AB  - BACKGROUND: The severe acute respiratory syndrome (SARS) spread rapidly around
      the world, largely because persons infected with the SARS-associated coronavirus
      (SARS-CoV) traveled on aircraft to distant cities. Although many infected persons
      traveled on commercial aircraft, the risk, if any, of in-flight transmission is
      unknown. METHODS: We attempted to interview passengers and crew members at least
      10 days after they had taken one of three flights that transported a patient or
      patients with SARS. All index patients met the criteria of the World Health
      Organization for a probable case of SARS, and index or secondary cases were
      confirmed to be positive for SARS-CoV on reverse-transcriptase polymerase chain
      reaction or serologic testing. RESULTS: After one flight carrying a symptomatic
      person and 119 other persons, laboratory-confirmed SARS developed in 16 persons,
      2 others were given diagnoses of probable SARS, and 4 were reported to have SARS
      but could not be interviewed. Among the 22 persons with illness, the mean time
      from the flight to the onset of symptoms was four days (range, two to eight), and
      there were no recognized exposures to patients with SARS before or after the
      flight. Illness in passengers was related to the physical proximity to the index
      patient, with illness reported in 8 of the 23 persons who were seated in the
      three rows in front of the index patient, as compared with 10 of the 88 persons
      who were seated elsewhere (relative risk, 3.1; 95 percent confidence interval,
      1.4 to 6.9). In contrast, another flight carrying four symptomatic persons
      resulted in transmission to at most one other person, and no illness was
      documented in passengers on the flight that carried a person who had
      presymptomatic SARS. CONCLUSIONS: Transmission of SARS may occur on an aircraft
      when infected persons fly during the symptomatic phase of illness. Measures to
      reduce the risk of transmission are warranted.

PMID- 14681508
TI  - Images in clinical medicine. Bleeding colonic diverticulum.

PMID- 14681509
TI  - Clinical practice. Genital chlamydial infections.

PMID- 14681510
TI  - The severe acute respiratory syndrome.

PMID- 14681511
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 39-2003. A 33-year-old woman with gross hematuria.

PMID- 14681512
TI  - Medical management of benign prostatic hyperplasia--are two drugs better than
      one?

PMID- 14681513
TI  - Academic-industrial relationships in the life sciences.

PMID- 14681514
TI  - Substitution for protease inhibitors in HIV therapy.

PMID- 14681515
TI  - Costs of health care administration in the United States and Canada.

PMID- 14681516
TI  - Sudden death in young athletes.

PMID- 14681517
TI  - Anatomy of a diagnosis.

PMID- 14681518
TI  - Myocardial bridging.

PMID- 14681519
TI  - Case 29-2003: a 60-year-old man with fever, rigors, and sweats.

PMID- 14681521
TI  - Estimated timing of the last common ancestor of the SARS coronavirus.

PMID- 14681520
TI  - Detection of SARS coronavirus in plasma by real-time RT-PCR.

PMID- 14681522
TI  - Images in clinical medicine. Giant Lambl's excrescences.

PMID- 14681523
TI  - Light signaling.

PMID- 14681524
TI  - Ultraviolet-B radiation-mediated responses in plants. Balancing damage and
      protection.

PMID- 14681525
TI  - Blue light signaling through the cryptochromes and phototropins. So that's what
      the blues is all about.

PMID- 14681526
TI  - The red side of photomorphogenesis.

PMID- 14681528
TI  - Internalizing the societal costs of agricultural production.

PMID- 14681527
TI  - Identification of promoter motifs involved in the network of phytochrome A
      regulated gene expression by combined analysis of genomic sequence and microarray
      data.
AB  - Several hundred Arabidopsis genes, transcriptionally regulated by phytochrome A
      (phyA), were previously identified using an oligonucleotide microarray. We have
      now identified, in silico, conserved sequence motifs in the promoters of these
      genes by comparing the promoter sequences to those of all the genes present on
      the microarray from which they were sampled. This was done using a Perl script
      (called Sift) that identifies over-represented motifs using an enumerative
      approach. The utility of Sift was verified by analysis of circadian-regulated
      promoters known to contain a biologically significant motif. Several elements
      were then identified in phyA-responsive promoters by their over-representation.
      Five previously undescribed motifs were detected in the promoters of phyA-induced
      genes. Four novel motifs were found in phyA-repressed promoters, plus a motif
      that strongly resembles the DE1 element. The G-box, CACGTG, was a prominent hit
      in both induced and repressed phyA-responsive promoters. Intriguingly, two
      distinct flanking consensus sequences were observed adjacent to the G-box core
      sequence: one predominating in phyA-induced promoters, the other in phyA
      repressed promoters. Such different conserved flanking nucleotides around the
      core motif in these two sets of promoters may indicate that different members of
      the same family of DNA-binding proteins mediate phyA induction and repression. An
      increased abundance of G-box sequences was observed in the most rapidly phyA
      responsive genes and in the promoters of phyA-regulated transcription factors,
      indicating that G-box-binding transcription factors are upstream components in a
      transcriptional cascade that mediates phyA-regulated development.

PMID- 14681529
TI  - Intellectual property resources for international development in agriculture.

PMID- 14681530
TI  - Tools to study plant organelle biogenesis. Point mutation lines with disrupted
      vacuoles and high-speed confocal screening of green fluorescent protein-tagged
      organelles.

PMID- 14681531
TI  - Plant gravitropism. Unraveling the ups and downs of a complex process.

PMID- 14681532
TI  - Glycosylphosphatidylinositol lipid anchoring of plant proteins. Sensitive
      prediction from sequence- and genome-wide studies for Arabidopsis and rice.
AB  - Posttranslational glycosylphosphatidylinositol (GPI) lipid anchoring is common
      not only for animal and fungal but also for plant proteins. The attachment of the
      GPI moiety to the carboxyl-terminus after proteolytic cleavage of a C-terminal
      propeptide is performed by the transamidase complex. Its four known subunits also
      have obvious full-length orthologs in the Arabidopsis and rice (Oryza sativa)
      genomes; thus, the mechanism of substrate protein processing appears similar for
      all eukaryotes. A learning set of plant proteins (substrates for the transamidase
      complex) has been collected both from the literature and plant sequence
      databases. We find that the plant GPI lipid anchor motif differs in minor aspects
      from the animal signal (e.g. the plant hydrophobic tail region can contain a
      higher fraction of aromatic residues). We have developed the "big-Pi plant"
      program for prediction of compatibility of query protein C-termini with the plant
      GPI lipid anchor motif requirements. Validation tests show that the sensitivity
      for transamidase targets is approximately 94%, and the rate of false positive
      prediction is about 0.1%. Thus, the big-Pi predictor can be applied as
      unsupervised genome annotation and target selection tool. The program is also
      suited for the design of modified protein constructs to test their GPI lipid
      anchoring capacity. The big-Pi plant predictor Web server and lists of potential
      plant precursor proteins in Swiss-Prot, SPTrEMBL, Arabidopsis, and rice proteomes
      are available at http://mendel.imp.univie.ac.at/gpi/plants/gpi_plants.html.
      Arabidopsis and rice protein hits have been functionally classified. Several GPI
      lipid-anchored arabinogalactan-related proteins have been identified in rice.

PMID- 14681533
TI  - Photosynthetic acclimation is reflected in specific patterns of gene expression
      in drought-stressed loblolly pine.
AB  - Because the product of a single gene can influence many aspects of plant growth
      and development, it is necessary to understand how gene products act in concert
      and upon each other to effect adaptive changes to stressful conditions. We
      conducted experiments to improve our understanding of the responses of loblolly
      pine (Pinus taeda) to drought stress. Water was withheld from rooted plantlets of
      to a measured water potential of -1 MPa for mild stress and -1.5 MPa for severe
      stress. Net photosynthesis was measured for each level of stress. RNA was
      isolated from needles and used in hybridizations against a microarray consisting
      of 2173 cDNA clones from five pine expressed sequence tag libraries. Gene
      expression was estimated using a two-stage mixed linear model. Subsequently, data
      mining via inductive logic programming identified rules (relationships) among
      gene expression, treatments, and functional categories. Changes in RNA transcript
      profiles of loblolly pine due to drought stress were correlated with
      physiological data reflecting photosynthetic acclimation to mild stress or
      photosynthetic failure during severe stress. Analysis of transcript profiles
      indicated that there are distinct patterns of expression related to the two
      levels of stress. Genes encoding heat shock proteins, late embryogenic-abundant
      proteins, enzymes from the aromatic acid and flavonoid biosynthetic pathways, and
      from carbon metabolism showed distinctive responses associated with acclimation.
      Five genes shown to have different transcript levels in response to either mild
      or severe stress were chosen for further analysis using real-time polymerase
      chain reaction. The real-time polymerase chain reaction results were in good
      agreement with those obtained on microarrays.

PMID- 14681534
TI  - Finding unexpected patterns in microarray data.
AB  - We describe the performance of a protocol based on the sequential application of
      unsupervised and supervised methods to analyze microarray samples defined by a
      combination of factors. Correspondence analysis is used to visualize the emerging
      patterns of three set of novel or previously published data: photoreceptor
      mutants of Arabidopsis grown under different light/dark conditions, Arabidopsis
      exposed to different types of biotic and abiotic stress, and human acute
      leukemia. We find, for instance, that light has a dramatic effect on plants
      despite the absence of the four major photoreceptors, that bacterial-, fungal-,
      and viral-induced responses converge at later stages of attack, and that sample
      preparation procedures used in different hospitals have large effects on
      transcriptome patterns. We use canonical discriminant analysis to identify the
      genes associated with these patters and hierarchical clustering to find groups of
      coregulated genes that are easily visualized in a second round of correspondence
      analysis and ordered tables. The unconventional combination of standard
      descriptive multivariate methods offers a previously unrecognized tool to uncover
      unexpected information.

PMID- 14681535
TI  - The Arabidopsis locus RCB mediates upstream regulation of mitotic gene
      expression.
AB  - Transcriptional regulation of cell cycle regulatory genes, such as B-type
      cyclins, is tightly linked with the mitotic activity in the meristems. To study
      the regulation of a B-type cyclin gene, a targeted genetic approach was
      undertaken. An Arabidopsis line containing a fusion construct between the CYCB1;1
      promoter and a bacterial beta-glucuronidase marker gene (uidA) was used in ethyl
      methanesulfonate mutagenesis. The mutants were screened for altered CYCB1;1::uidA
      expression patterns. In a reduced CYCB1;1 expression mutant (rcb), the
      CYCB1;1::uidA expression was severely affected, being excluded from the shoot and
      root apical meristems and leaf primordia and shifted to cells associated with
      root cap and stomata. In addition to the overall reduction of the endogenous
      CYCB1;1 transcript levels, other G2-to-M phase-specific genes were also down
      regulated by the mutation. In the mutant plants, the inflorescence stem growth
      was reduced, indicating low meristem activity. Based on the altered CYCB1;1::uidA
      expression patterns in rcb root meristem, a model is proposed for RCB that
      mediates the tissue specificity of CYCB1;1 promoter activity.

PMID- 14681536
TI  - Light control of nuclear gene mRNA abundance and translation in tobacco.
AB  - Photosynthetic signals modulate expression of nuclear genes at the levels of mRNA
      transcription, mRNA stability, and translation. In transgenic tobacco (Nicotiana
      tabacum), the pea (Pisum sativum) Ferredoxin 1 (Fed-1) mRNA dissociates from
      polyribosomes and becomes destabilized when photosynthesis is inhibited by
      photosynthetic electron transport inhibitor 3-(3,4-dichlorophenyl)-1,1
      dimethylurea. We used polymerase chain reaction suppressive-subtractive
      hybridization to identify similarly regulated endogenous tobacco genes. This
      screen identified 14 nuclear-encoded tobacco mRNAs whose light-induced increase
      in abundance is suppressed in the presence of 3-(3,4-dichlorophenyl)-1,1
      dimethylurea. Sequence analysis of the cognate cDNAs revealed that nine of the
      mRNAs encode putative chloroplast-targeted proteins. We asked whether the
      abundance of these mRNAs was regulated transcriptionally or
      posttranscriptionally. Of the five mRNAs with sufficient abundance to detect
      using nuclear run-on assays, we observed transcriptional regulation of alpha
      tubulin, thiazole biosynthetic enzyme, and pSKA10 (an unknown gene). Photosystem
      A subunit L and, to a lesser extent, alpha-tubulin and pSKA10 mRNAs, may also be
      stabilized in the light. In contrast, Rubisco small subunit mRNA abundance
      appears to be transcriptionally up-regulated but posttranscriptionally down
      regulated in the light. To determine whether, like Fed-1 mRNA, the mRNAs
      identified in this screen were translationally responsive to light, we
      characterized the polyribosome association of these mRNAs in the light and after
      a 15-min dark treatment. A subset of the mRNAs showed dramatic dark-induced
      polyribosome dissociation, similar to Fed-1 mRNA, and all of the mRNAs showed at
      least slight polyribosome dissociation. Thus, both posttranscriptional and
      translational regulation appear to be important mechanisms regulating the
      expression of many nuclear-encoded mRNAs encoding proteins involved in
      photosynthesis.

PMID- 14681539
TI  - Physician-scientists: preparation, opportunities, and national need.

PMID- 14681537
TI  - Phosphorylated non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase from
      heterotrophic cells of wheat interacts with 14-3-3 proteins.
AB  - Glyceraldehyde-3-phosphate dehydrogenases catalyze key steps in energy and
      reducing power partitioning in cells of higher plants. Phosphorylated non
      phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN) present in
      heterotrophic cells of wheat (Triticum aestivum) was activated up to 3-fold by
      MgCl2. The effect was not observed with the non-phosphorylated enzyme found in
      leaves. The divalent cation also affected the response of the enzyme from
      endosperm and shoots to adenine nucleotides and inorganic pyrophosphate. Gel
      filtration chromatography, co-immunoprecipitation followed by immunostaining, and
      the use of a phosphopeptide containing a canonical binding motif showed that
      MgCl2 actually disrupted the interaction between GAPN and a 14-3-3 regulatory
      protein. After interaction with 14-3-3, phosphorylated GAPN exhibits a 3-fold
      lower Vmax and higher sensitivity to inhibition by ATP and pyrophosphate. Results
      suggest that GAPN is a target for regulation by phosphorylation, levels of
      divalent cations, and 14-3-3 proteins. The regulatory mechanism could be critical
      to maintain levels of energy and reductants in the cytoplasm of heterotrophic
      plant cells.

PMID- 14681540
TI  - Career choices in the biosciences: what companies are looking for when they are
      filling a position.
AB  - Holding a Ph.D. or other doctoral degree in the biological sciences used to allow
      for only one main career path. Faculty positions at either research-intensive
      universities or at predominantly teaching institutions defined the career path
      very well. The situation is considerably more complex now. Many individuals
      decide to pursue careers in for-profit organizations, either by personal
      preference, geographic needs, or simply as an expedient way to continue in
      biology in a meaningful way. This article arises from the need to define a better
      understanding of the nature of corporate job seeking for potential job
      applicants. The author draws upon his experience over a thirty-year scientific
      career in industry and academics. The distinctions he makes are helpful for job
      seekers in this new environment.

PMID- 14681541
TI  - Two-career families: published data and personal reflections.

PMID- 14681542
TI  - Building and supporting effective academic clinical research programs in today's
      market-driven health care environment: is research valued and how much and by
      whom?

PMID- 14681544
TI  - The role of GATA in mammalian reproduction.
AB  - GATA transcription factors are emerging as critical players in mammalian
      reproductive development and function. GATA-4 contributes to fetal male gonadal
      development by regulating genes mediating Mullerian duct regression and the onset
      of testosterone production. GATA-2 expression appears to be sexually dimorphic
      being transiently expressed in the germ cell lineage of the fetal ovary but not
      the fetal testis. In the reproductive system, GATA-1 is exclusively expressed in
      Sertoli cells at specific seminiferous tubule stages. In addition, GATA-4 and
      GATA-6 are localized primary to ovarian and testicular somatic cells. The
      majority of cell transfection studies demonstrate that GATA-1 and GATA-4 can
      stimulate inhibin subunit gene promoter constructs. Other studies provide strong
      evidence that GATA-4 and GATA-6 can activate genes mediating gonadal cell
      steroidogenesis. GATA-2 and GATA-3 are found in pituitary and placental cells and
      can regulate alpha-glycoprotein subunit gene expression. Gonadal expression and
      activation of GATAs appear to be regulated in part by gonadotropin signaling via
      the cyclic AMP-protein kinase A pathway. This review will cover the current
      knowledge regarding GATA expression and function at all levels of the
      reproductive axis.

PMID- 14681545
TI  - Tetrahydrobiopterin and nitric oxide: mechanistic and pharmacological aspects.
AB  - In previous minireviews in this journal, we discussed work on induction of
      tetrahydrobiopterin biosynthesis by cytokines and its significance for nitric
      oxide (NO) production of intact cells as well as functions of H4-biopterin
      identified at this time for NO synthases (Proc Soc Exp Biol Med 203: 1-12, 1993;
      Proc Soc Exp Biol Med 219: 171-182, 1998). Meanwhile, the recognition of the
      importance of tetrahydrobiopterin for NO formation has led to new insights into
      complex biological processes and revealed possible novel pharmacological
      strategies to intervene in certain pathological conditions. Recent work could
      also establish that tetrahydrobiopterin, in addition to its allosteric effects,
      is redox-active in the NO synthase reaction. In this review, we summarize the
      current view of how tetrahydrobiopterin functions in the generation of NO and
      focus on pharmacological aspects of tetrahydrobiopterin availability with
      emphasis on endothelial function.

PMID- 14681546
TI  - Dietary dehydroepiandrosterone inhibits bone marrow and leukemia cell
      transplants: role of food restriction.
AB  - Dietary dehydroepiandrosterone (DHEA) inhibits the proliferation of syngeneic
      bone marrow cells (BMC) infused into lethally irradiated mice. Potential
      mechanisms for suppression of hematopoiesis were evaluated and the findings were
      as follows: (i) depletion of NK, T, B or macrophage cells failed to reverse
      suppression by DHEA; (ii) stem cell stimulation by erythropoietin, growth
      hormone, interleukin-2, Friend leukemia virus, or cyclophosphamide failed to
      reverse suppression; (iii) supplementation of fatty acids, mevalonate, or
      deoxyribonucleotides, which are dependent upon glucose-6-phosphate dehydrogenase
      function, did not enhance BMC growth in mice fed DHEA; (iv) DHEA downstream
      metabolites 4-androstenedione and 17beta-estradiol, as well as the synthetic
      steroid, 16alpha-chloroepiandrosterone (but not testosterone or 5-androstene
      3beta,17beta-diol), also inhibited BMC growth. Tamoxifen antagonized the effects
      of 17beta-estradiol but not DHEA; (v) dietary DHEA causes hypothermia, but
      housing of DHEA-fed mice at 34 degrees C to maintain normal body temperature did
      not reverse suppression; (vi) DHEA leads to a decrease in food intake in rodents.
      Pair-feeding control diet to mice fed DHEA mimicked the effects of dietary DHEA;
      (vii) adrenalectomy and orchiectomy decrease the levels of stress and sex
      hormones, respectively. Neither procedure affected the ability of food
      restriction or DHEA feeding to inhibit hematopoiesis; (viii) growth of GR-3 NM
      pre-B leukemia cells in unirradiated mice was also suppressed by DHEA or food
      restriction. We conclude that DHEA, by reducing food intake in mice, inhibits
      bone marrow and leukemia cell growth. The precise mechanism(s) by which reduced
      food intake per se inhibits hematopoiesis is not known, but may involve an
      increased rate of cellular apoptosis.

PMID- 14681543
TI  - Proteins of multiple classes may participate in nongenomic steroid actions.
AB  - Responses to steroids initiated from non-nuclear receptors impinge on a wide
      variety of cellular responses and utilize nearly all known signal transduction
      webs. While the mechanisms by which steroid receptors localize in the membrane
      are still unclear, it is apparent that this alternative localization allows
      steroid receptors to participate in a wide range of complex functions influencing
      cell proliferation, death, and differentiation. The central debate still remains
      the identity of the protein class or classes that mediate membrane-initiated
      (nongenomic) responses. The data thus far have supported several possibilities,
      including: nuclear steroid receptor-like forms in non-nuclear locations; other
      known (nonsteroid) membrane receptors or channels with additional steroid-binding
      sites; enzymes; transporters; receptors for serum steroid-binding proteins;
      unique and previously undescribed proteins; or chimeras of typical steroid
      receptor domains with other unique or known protein domains. Categorizing
      membrane steroid receptor proteins based exclusively on the actions of
      antagonists and agonists, without considering cell context and protein partnering
      issues, may mislead us into predicting more receptor subtypes than really exist.
      However, the plethora of signaling and functional outcomes may indicate the
      participation of more than one kind of steroid-binding protein. Resolving such
      unanswered questions will require future investigative focus on this alternative
      arm of steroid action, which is likely to yield as many therapeutic opportunities
      as have nuclear steroid mechanisms.

PMID- 14681547
TI  - Inhibitory mechanisms of metallothionein on platelet aggregation in in vitro and
      platelet plug formation in in vivo experiments.
AB  - Metallothionein (MT) is a low-molecular-weight, cysteine-rich protein that
      contains heavy metals such as cadmium and zinc. The biological function of MT in
      platelets is not yet understood. Therefore, the aim of this study was to
      systematically examine the inhibitory mechanisms of metallothionein in platelet
      aggregation. In this study, metallothionein concentration-dependently (1-8
      microM) inhibited platelet aggregation in human platelets stimulated by agonists.
      Metallothionein (4 and 8 microM) inhibited phosphoinositide breakdown in [3H]
      inositol-labeled platelets, intracellular Ca+2 mobilization in Fura-2 AM-loaded
      platelets, and thromboxane A2 formation stimulated by collagen. In addition,
      metallothionein (4 and 8 microM) significantly increased the formation of cyclic
      GMP but not cyclic AMP in human platelets. Rapid phosphorylation of a protein of
      Mr 47,000 (P47), a marker of protein kinase C activation, was triggered by PDBu
      (100 nM). This phosphorylation was markedly inhibited by metallothionein (4 and 8
      microM) in phosphorus-32-labeled platelets. In an in vivo thrombotic study,
      platelet thrombus formation was induced by irradiation of mesenteric venules in
      mice pretreated with fluorescein sodium. Metallothionein (6 microg/g)
      significantly prolonged the latency period for inducing platelet plug formation
      in mesenteric venules. These results indicate that the antiplatelet activity of
      metallothionein may involve the following pathways: (1) metallothionein may
      inhibit the activation of phospholipase C, followed by inhibition of
      phosphoinositide breakdown and thromboxane A2 formation, thereby leading to
      inhibition of intracellular Ca+2 mobilization; (ii) Metallothionein also
      activated the formation of cyclic GMP in human platelets, resulting in inhibition
      of platelet aggregation. The results strongly indicate that metallothionein
      provides protection against thromboembolism.

PMID- 14681548
TI  - Wound healing and angiogenic properties of supernatants from Lactobacillus
      cultures.
AB  - Extracts or supernatants from cultures of Lactobacilli are used for their
      medicinal effects, including wound healing and immune system stimulating
      activity. We have studied the in vivo and in vitro effects of supernatants from
      bacterial cultures of two strains of Lactobacillus (LS) on tissue repair and
      angiogenesis. Subcutaneous injection of LS into rodent ears led to proliferation
      of blood vessels that also exhibited strong immunostaining for Flk-1 receptor.
      Some inflammatory cells were scattered among the blood vessels. The continuous
      influx of polymorphonuclear leukocytes (PMNs) and macrophages into transcutaneous
      wounds in mice treated with LS resulted in prolonged inflammatory phase of wound
      healing and delayed wound closure, including reepithelialization. Subcutaneous
      injection of Matrigel impregnated with LS into the abdominal wall led to rapid
      and transient influx of PMNs in the vicinity of the gel. LS stimulated the
      proliferation of murine macrophage J774.A1 cell line and porcine lymphocytes but
      not that of murine fibroblast AKR-2B cells. LS also induced production of TNF
      alpha by J774.A1 cells and by porcine kidney epithelial LLC-PK1 cells. LS did not
      appear to have an effect on collagen production. In conclusion, our study
      demonstrates the potential of LS to function as a stimulator of the inflammatory
      stage of tissue repair, TNF-alpha production, and of angiogenesis.

PMID- 14681549
TI  - Anti-hyperglycemic activity of zinc plus cyclo (his-pro) in genetically diabetic
      Goto-Kakizaki and aged rats.
AB  - We previously reported that treatment of streptozotocin-induced diabetic rats
      with zinc plus cyclo (his-pro) (CHP) decreased fed blood glucose levels and water
      intake. The present study was conducted to examine the dose-dependent, acute, and
      chronic treatment effects of CHP on oral glucose tolerance (OGT), fed blood
      glucose levels, water intake, and plasma insulin levels in young and aged Sprague
      Dawley (S-D) rats, nondiabetic Wistar rats, and genetically diabetic Goto
      Kakizaki (G-K) rats. Acute gastric gavage of 10 mg zinc plus 1.0 mg CHP/kg body
      weight significantly improved OGT in 4- and 13-month-old nondiabetic S-D rats and
      in 2-month-old diabetic G-K rats. Young S-D and G-K rats returned to pretreatment
      OGT values 1 week after acute gavage of zinc plus CHP (ZC), but improved OGT
      values persisted for at least 1 week after gavage in aged S-D rats. OGT values
      and fed blood glucose decreased to the greatest extent among other treatments
      when G-K rats were given free access to drinking water containing 1.0 to 1.5 mg
      CHP/L plus 10 mg zinc/L for 2 weeks. Although food and water intake showed a
      tendency to decrease, no statistically significant differences were observed in
      young G-K rats. Plasma insulin levels and blood glucose levels in both normal and
      diabetic G-K rats decreased with 2-week treatment with ZC. To test the direct
      effects of ZC on muscle tissue, we observed the effect of various doses of ZC on
      normal and G-K rat muscle slices. The optimal level of CHP alone for maximal
      muscle glucose uptake in muscle slices from normal rats was 10 microg/mL and 5.0
      microg/mL in G-K rats, and ZC stimulated glucose uptake. However, no
      statistically significant difference was demonstrated between normal and G-K rat
      tissues in this study. These results indicate that oral intake of an optimal dose
      of ZC stimulates blood glucose metabolism, probably by stimulating muscle glucose
      utilization.

PMID- 14681550
TI  - Different sensitivity to apoptosis in cells of monocytic or lymphocytic origin
      chronically infected with human immunodeficiency virus type-1.
AB  - Apoptotic death of CD4+ T lymphocytes is a major cause of the immunodeficiency
      caused by human immunodeficiency virus (HIV), but it is still unclear how this
      process precisely occurs. To characterize a potentially useful cellular model, we
      have analyzed the tendency of chronically HIV-infected CD4+ human cell lines of
      different origin to undergo apoptosis. We studied ACH-2 and U1 lines, derived
      from the CD4+ T-cell A301 and the promonocytic U937 cell lines, respectively, and
      induced apoptosis via several stimuli that trigger different pathways. Their
      capacity to regulate plasma membrane CD95 expression and to produce soluble CD95
      was also analyzed. Using staurosporine, TNF-alpha plus cycloheximide, and gamma
      radiations, we observed that ACH-2 were more sensitive to programmed cell death
      than A301, while U1 were less sensitive than U937. Both infected cell types had a
      lower sensitivity to CD95-induced apoptosis; the analysis of changes in
      mitochondrial membrane potential corroborated these observations. Plasma membrane
      CD95 was similarly regulated in all cell types, which, however, presented a
      different capacity to produce soluble CD95 molecules. Our in vitro results may
      offer a new perspective for developing further studies on the pathogenesis of HIV
      infection. A chronically infected cell line of lymphocytic origin is more
      susceptible to apoptosis than its parental cell type, while infected monocytic
      cells are less sensitive than their uninfected counterpart. Thus, it is possible
      to hypothesize that one of the reasons by which circulating monocytes survive and
      represent a viral reservoir is the capacity of HIV to decrease the sensitivity to
      apoptosis of this cell type. However, further studies on ex-vivo collected fresh
      cells, as well as on other cell lines, are urgently needed to confirm such
      hypothesis.

PMID- 14681551
TI  - Clinical follow-up in the rat experimental model of African trypanosomiasis.
AB  - Animal models of Human African Trypanosomiasis (HAT) have been developed to
      understand the pathogenic mechanisms leading to the passage into the neurological
      phase, most of them referring to histological aspects but not clinical or
      behavioral data. Our study aimed at defining simple clinical and/or behavioral
      markers of the passage between the hemolymphatic phase and the meningo
      encephalitic stage of the disease. Sprague-Dawley rats (n=24) were infected with
      Trypanosoma brucei brucei AnTat 1.1E. Food intake and body weight were measured
      daily from the day of infection until death. Hematocrit was measured twice a
      week. Behavioral disturbances were evaluated through an Open-field test. A sudden
      weight loss occurred on the twelfth day after infection, due to a significant
      drop of food intake starting two days before. The rats developed an anemic state
      shown by the hematocrit measurements. The Open-field test showed them to be less
      active and reactive as soon as the second week after infestation. A complementary
      histological study observed trypanosomes and inflammatory cells in the choroid
      plexus at the same period. These results are in favor of central nervous system
      functional disturbances. The observed weight loss is discussed as being a
      parameter of the entry in the meningo-encephalitic phase. The rat model
      reproduces neurological symptoms observed in the human disease and may prove to
      be useful for further neurohistological and therapeutic studies.

PMID- 14681552
TI  - ATP-dependent interaction of the cytosolic domains of the inwardly rectifying K+
      channel Kir6.2 revealed by fluorescence resonance energy transfer.
AB  - ATP-sensitive K(+) (K(ATP)) channels play important roles in the regulation of
      membrane excitability in many cell types. ATP inhibits channel activity by
      binding to a specific site formed by the N and C termini of the pore-forming
      subunit, Kir6.2, but the structural changes associated with this interaction
      remain unclear. Here, we use fluorescence resonance energy transfer (FRET) to
      study the ATP-dependent interaction between the N and C termini of Kir6.2 using a
      construct bearing fused cyan and yellow fluorescent proteins (ECFP-Kir6.2-EYFP).
      When expressed in human embryonic kidney cells, ECFP-Kir6.2-EYFP/SUR1 channels
      displayed FRET that was augmented by agonist stimulation and diminished by
      metabolic poisoning. Addition of ATP to permeabilized cells or isolated plasma
      membrane sheets increased FRET. FRET changes were abolished by Kir6.2 mutations
      that altered ATP-dependent channel closure and channel gating. In the wild-type
      channel, the ATP concentrations, which increased FRET (EC(50) = 1.36 mM), were
      significantly higher than those causing channel inhibition (IC(50) = 0.29 mM).
      Demonstrating the existence of intermolecular interactions, a dimeric construct
      comprising two molecules of Kir6.2 linked head-to-tail (ECFP-Kir6.2-Kir6.2-EYFP)
      displayed less FRET than the monomer in the absence of nucleotide but still
      exhibited ATP-dependent FRET increases (EC(50) = 1.52 mM) and channel inhibition.
      We conclude that binding of ATP to Kir6.2, (i). alters the interaction between
      the N- and C-terminal domains, (ii). probably involves both intrasubunit and
      intersubunit interactions, (iii). reflects ligand binding not channel gating, and
      (iv). occurs in intact cells when subplasmalemmal [ATP] changes in the millimolar
      range.

PMID- 14681553
TI  - Selective abolition of pancreatic RNase binding to its inhibitor protein.
AB  - We have modified RNase inhibitor (RI) protein so that it no longer detectably
      binds pancreatic RNases but retains near-native affinity for human angiogenin
      (ANG). The K(i) value for RNase A is increased by a factor of >10(8), from 36 fM
      to >4 microM, and the selectivity factor for ANG is now >10(9). This dramatic
      change was achieved by remodeling the human RI loop segment Cys-408 -Leu-409 -Gly
      410, which makes minor interactions with pancreatic RNase but does not contact
      ANG. The modifications selected were designed to sterically hinder docking of the
      undesired ligand. Three of the variants tested (C408W, G410W, and C408W/G410W)
      bind RNase A with almost the same avidity as WT RI. However, combination of the
      408/410 double Trp replacement with deletion of the intervening residue, Leu-409,
      was sufficient to abolish inhibition of RNase A and human pancreatic RNase. The
      K(i) value for ANG with the deletion variant is 1.1 fM, only 2-fold higher than
      with WT RI. This variant may have potential utility both as an anticancer drug
      targeting ANG and as a tool for the investigation of the biological function of
      ANG. More generally, these findings demonstrate that a protein-protein
      interaction can be effectively and specifically disrupted by redesigning an
      interface region that makes no major energetic contribution to complex stability.
      This finding, in turn, may have implications for the development of small
      molecules that modulate protein-protein interactions.

PMID- 14681554
TI  - Alleviating spatial conflict between people and biodiversity.
AB  - Human settlements are expanding in species-rich regions and pose a serious threat
      to biodiversity conservation. We quantify the degree to which this threat
      manifests itself in two contrasting continents, Australia and North America, and
      suggest how it can be substantially alleviated. Human population density has a
      strong positive correlation with species richness in Australia for birds,
      mammals, amphibians, and butterflies (but not reptiles) and in North America for
      all five taxa. Nevertheless, conservation investments could secure locations that
      harbor almost all species while greatly reducing overlap with densely populated
      regions. We compared two conservation-planning scenarios that each aimed to
      represent all species at least once in a minimum set of sampling sites. The first
      scenario assigned equal cost to each site (ignoring differences in human
      population density); the second assigned a cost proportional to the site's human
      population density. Under the equal-cost scenario, 13-40% of selected sites
      occurred where population density values were highest (in the top decile).
      However, this overlap was reduced to as low as 0%, and in almost all cases to
      <10%, under the population-cost scenario, when sites of high population density
      were avoided where possible. Moreover, this reduction of overlap was achieved
      with only small increases in the total amount of area requiring protection. As
      densely populated regions continue to expand rapidly and drive up land values,
      the strategic conservation investments of the kind highlighted in our analysis
      are best made now.

PMID- 14681555
TI  - Anatomy of a chaotic attractor: subtle model-predicted patterns revealed in
      population data.
AB  - Mathematically, chaotic dynamics are not devoid of order but display episodes of
      near-cyclic temporal patterns. This is illustrated, in interesting ways, in the
      case of chaotic biological populations. Despite the individual nature of
      organisms and the noisy nature of biological time series, subtle temporal
      patterns have been detected. By using data drawn from chaotic insect populations,
      we show quantitatively that chaos manifests itself as a tapestry of identifiable
      and predictable patterns woven together by stochasticity. We show too that the
      mixture of patterns an experimentalist can expect to see depends on the scale of
      the system under study.

PMID- 14681557
TI  - Biomimetic ratcheting motion of a soft, slender, sessile gel.
AB  - Inspired by the locomotion of terrestrial limbless animals, we study the motion
      of a lubricated rod of a hydrogel on a soft substrate. We show that it is
      possible to mimic observed biological gaits by vibrating the substrate and by
      using a variety of mechanisms to break longitudinal and lateral symmetry. Our
      simple theory and experiments provide a unified view of the creeping, undulating,
      and inchworming gaits observed in limbless locomotion on land, all of which
      originate as symmetry-breaking bifurcations of a simple base state associated
      with periodic longitudinal oscillations of a slender gel. These ideas are
      therefore also applicable to technological situations that involve moving small,
      soft solids on substrates.

PMID- 14681556
TI  - T cell chemotaxis to lysophosphatidylcholine through the G2A receptor.
AB  - G2A is an immunoregulatory G protein-coupled receptor predominantly expressed in
      lymphocytes and macrophages. Ectopic overexpression studies have implicated G2A
      as a receptor for the bioactive lysophospholipid, lysophosphatidylcholine (LPC).
      However, the functional consequences of LPC-G2A interaction at physiological
      levels of receptor expression, and in a cellular context relevant to its
      immunological role, remain largely unknown. Here, we show impaired chemotaxis to
      LPC of a T lymphoid cell line in which G2A expression was chronically down
      regulated by RNA interference technology. Rescuing this phenotype by
      reconstitution of the physiological level of receptor expression further supports
      a functional connection between LPC-G2A interaction and cellular motility.
      Overexpression of G2A in the T lymphoid cell line significantly enhanced
      chemotaxis to LPC. It also modified migration toward the LPC-related molecule,
      lysophosphatidic acid, indicating the possibility of crosstalk between G2A and
      endogenous lysophosphatidic acid receptors. The role of G2A in LPC-mediated cell
      migration may be relevant to the autoimmune syndrome associated with genetic
      inactivation of this G protein-coupled receptor in mice. The experimental system
      described here can be useful for understanding the structural requirements for
      LPC recognition by G2A and the signaling pathways regulated by this ligand
      receptor pair.

PMID- 14681559
TI  - (Richard) Michael Mason, MA, DM, FRCP (1917-1977).

PMID- 14681560
TI  - Common NOD2 polymorphisms in Hong Kong Chinese patients with systemic lupus
      erythematosus.

PMID- 14681561
TI  - Safety monitoring for disease-modifying anti-rheumatic drugs in primary and
      secondary care: adherence to local and national guidelines and patients' views.

PMID- 14681563
TI  - Rheumatoid arthritis impairs driving ability even in patients with a low
      disability index.

PMID- 14681562
TI  - Polymorphism of the tumour necrosis factor-alpha gene at position -308 and renal
      manifestations of primary Sjogren's syndrome.

PMID- 14681564
TI  - Interstitial nephritis with infiltration of IgG-kappa positive plasma cells in a
      patient with Sjogren's syndrome.

PMID- 14681565
TI  - Pyrexia, pelvic pain and thrombocytopenia in an Asian man with Paget's disease of
      bone.

PMID- 14681566
TI  - Opportunistic infection due to unexplained CD4+ lymphocytopenia and associated
      Sjogren's syndrome.

PMID- 14681567
TI  - From the outside of Plato's cave.

PMID- 14681568
TI  - Ischaemic heart disease in rheumatoid arthritis patients.

PMID- 14681570
TI  - Symptom concealment--a new phenomenon in patients treated with biological
      therapies?

PMID- 14681572
TI  - Infections and anti-TNF therapy: strategies for screening based on clinical
      experience.

PMID- 14681575
TI  - Power to the people.

PMID- 14681576
TI  - Cyclin-dependent kinase 5--a neuronal killer?
AB  - In dividing cells, cyclin-dependent kinases (Cdks) are cell cycle-associated
      protein kinases that regulate proliferation, differentiation, senescence, and
      apoptosis. In neurons that no longer divide, deregulation of Cdks, especially
      Cdk5, occurs in many neurological disorders, including Alzheimer's disease (AD)
      and Parkinson's disease (PD). Cdk5 is a unique member of the Cdk family because
      it does not play a critical role in cell cycle progression, and it is not
      activated by a cyclin. Instead, Cdk5 normally is activated by the regulatory
      protein p35. This Cdk5/p35 activity has emerged as an important regulator of
      proper development of the mammalian central nervous system. In vitro studies
      suggest that aberrant activation of Cdk5 by an endogenous truncated version (p25)
      of p35 might be a key event in the process of neurodegeneration. One enzyme
      responsible for cleavage of p35 to form p25 is calpain, a calcium-activated
      protease that has been shown to be involved in neuronal cell death. Recent
      studies provided important in vivo evidence that hyperactivation and
      redistribution of Cdk5 by p25 plays an essential role in the phosphorylation of
      "pathological" substrates (such as tau) and the cell death of neurons in
      experimental models of AD and PD. Because amyloid beta peptide, the primary
      neurotoxic component of amyloid plaques in AD, has been shown to increase the
      conversion of p35 to p25, aberrant activation of Cdk5 by p25 might be a pathway
      connecting amyloid beta toxicity to tau hyperphosphorylation in AD.

PMID- 14681577
TI  - Regulation of splicing: the importance of being translatable.
AB  - RNA sequences that conform to the consensus sequence of 5' splice sites but are
      not used for splicing occur frequently in protein coding genes. Mutational
      analyses have shown that suppression of splicing at such latent sites may be
      dictated by the necessity to maintain an open reading frame in the mRNA. Here we
      show that stop codon frequency in introns having latent 5' splice sites is
      significantly greater than that of introns lacking such sites and significantly
      greater than the expected occurrence by chance alone. Both observations suggest
      the occurrence of a general mechanism that recognizes the mRNA reading frame in
      the context of pre-mRNA.

PMID- 14681578
TI  - Latent splice sites and stop codons revisited.
AB  - The accuracy of the data we reported in an RNA Letter to the Editor earlier this
      year on the possible relationship between stop codons and splicing is questioned
      by Miriami et al. (this issue). We reply here that we see no inaccuracy in our
      data presentation and offer a possible explanation for their interpretation.

PMID- 14681579
TI  - Aptamer redesigned tRNA is nonfunctional and degraded in cells.
AB  - An RNA aptamer derived from tRNA(Gln) isolated in vitro and a rationally
      redesigned tRNA(Gln) were used to address the relationship between structure and
      function of tRNA(Gln) aminoacylation in Escherichia coli. Two mutant tRNA(Gln)
      sequences were studied: an aptamer that binds 26-fold tighter to glutaminyl-tRNA
      synthetase than wild-type tRNA(Gln) in vitro, redesigned in the variable loop,
      and a mutant with near-normal aminoacylation kinetics for glutamine, redesigned
      to contain a long variable arm. Both mutants were tested in a tRNA(Gln) knockout
      strain of E. coli, but neither supported knockout cell growth. It was later found
      that both mutant tRNAs were present in very low amounts in the cell. These
      results reveal the difference between in vitro and in vivo studies, demonstrating
      the complexities of in vivo systems that have not been replicated in vitro.

PMID- 14681580
TI  - Nonspecific, concentration-dependent stimulation and repression of mammalian gene
      expression by small interfering RNAs (siRNAs).
AB  - RNA interference is an evolutionarily conserved process in which expression of a
      specific gene is post-transcriptionally inhibited by a small interfering RNA
      (siRNA), which recognizes a complementary mRNA and induces its degradation.
      Currently, RNA interference is being used extensively to inhibit expression of
      specific genes for experimental and therapeutic purposes. For applications in
      mammalian cells, siRNAs are designed to be <approximately 30 base pairs to avoid
      nonspecific effects that arise from inducing the cellular double-stranded RNA
      (dsRNA)-dependent protein kinase (PKR) response. Here we perform expression
      profiling in mammalian tissue-culture cells treated under standard conditions
      with conventional 21-bp siRNAs and find, unexpectedly, that >1000 genes involved
      in diverse cellular functions are nonspecifically stimulated or repressed. The
      effects on gene expression are dependent upon siRNA concentration and are stable
      throughout the course of siRNA treatment. Our results can be explained by
      previous studies showing that dsRNAs can affect multiple signaling and
      transcription pathways in addition to PKR. The potential for this widespread,
      nonspecific effect on mammalian gene expression must be carefully considered in
      the design of siRNA experiments and therapeutic applications.

PMID- 14681581
TI  - The RNA binding domain within the nucleoporin Nup153 associates preferentially
      with single-stranded RNA.
AB  - The nuclear pore protein Nup153 is important for the transport of protein and RNA
      between the nucleus and cytoplasm. Recently, a novel RNA binding domain (RBD) was
      mapped within the N-terminal region of Nup153; however, the determinants of RNA
      association were not characterized. Here we have tested a range of RNAs with
      different general features to better understand targets recognized by this
      domain. We have found that the RBD associates with single-stranded RNA with
      little sequence preference. These results provide new information about a novel
      RNA binding domain and suggest new models to consider for the contribution of
      Nup153 to nucleocytoplasmic transport.

PMID- 14681582
TI  - Genetic evidence against the 16S ribosomal RNA helix 27 conformational switch
      model.
AB  - A mechanistic understanding of ribosome function demands knowledge of the
      conformational changes that occur during protein synthesis. One current model
      proposes a conformational switch in Helix 27 (H27) of 16S rRNA involved in the
      decoding of mRNA. This model was based on the behavior of mutations in the 912
      region of H27 of Escherichia coli 16S rRNA, which were predicted to stabilize the
      helix in either of two alternative conformations. This interpretation was
      supported by evidence from both genetics and structural biochemistry. However,
      recently published X-ray crystallographic structures of the Thermus thermophilus
      30S subunit at different stages of tRNA selection have raised doubts regarding
      the validity of this model. We have therefore revisited the model genetically by
      constructing a H27 quadruple mutation (C912G, C910G, G885C, and G887C), which
      would create multiple mismatches in the proposed alternative conformation without
      perturbing the native H27 conformation seen in the crystal structures.
      Inconsistent with the H27 switch model, cells containing pure populations of
      quadruple mutant ribosomes grow at essentially wild-type rates. The mutants used
      to construct the H27 switch model all carried A2058G in 23S rRNA and C1192U in
      16S rRNA as selectable markers. The quadruple mutant carrying these additional
      marker mutations is deleterious, and we conclude that they have a synergistic
      effect when combined with other mutations and are not phenotypically silent.
      Their presence confounded the interpretation of the original mutant phenotypes
      and, in light of the viability of the quadruple mutant, we conclude that the
      genetic evidence no longer supports the model.

PMID- 14681583
TI  - Dynamics of the IRE RNA hairpin loop probed by 2-aminopurine fluorescence and
      stochastic dynamics simulations.
AB  - The iron responsive element (IRE) RNA hairpin loop contains six phylogenetically
      conserved nucleotides, which constitute part of the sequence-specific binding
      site of the IRE-binding protein. The NMR structure of the loop has been solved,
      showing that 3 of the 6 nt are poorly constrained. Here, two purine nucleotides
      in the IRE loop are individually replaced with the fluorescent purine analog 2
      aminopurine (2AP). Steady-state and time-resolved fluorescence methods are used
      to describe the structure and dynamics of 2AP in the IRE loop. The data indicate
      that 2AP at the position of the adenosine in the loop moves between stacked and
      unstacked positions, whereas 2AP at the adjacent guanosine is predominantly
      solvent exposed. Stochastic dynamics simulations are used to provide a physical
      description of how those nucleotides might move.

PMID- 14681584
TI  - Spatial determinants of the alfalfa mosaic virus coat protein binding site.
AB  - The biological functions of RNA-protein complexes are, for the most part, poorly
      defined. Here, we describe experiments that are aimed at understanding the
      functional significance of alfalfa mosaic virus RNA-coat protein binding, an
      interaction that parallels the initiation of viral RNA replication. Peptides
      representing the RNA-binding domain of the viral coat protein are biologically
      active in initiating replication and bind to a 39-nt 3'-terminal RNA with a
      stoichiometry of two peptides: 1 RNA. To begin to understand how RNA-peptide
      interactions induce RNA conformational changes and initiate replication, the AMV
      RNA fragment was experimentally manipulated by increasing the interhelical
      spacing, by interrupting the apparent nucleotide symmetry, and by extending the
      binding site. In general, both asymmetric and symmetric insertions between two
      proposed hairpins diminished binding, whereas 5' and 3' extensions had minimal
      effects. Exchanging the positions of the binding site hairpins resulted in only a
      moderate decrease in peptide binding affinity without changing the hydroxyl
      radical footprint protection pattern. To assess biological relevance in viral RNA
      replication, the nucleotide changes were transferred into infectious genomic RNA
      clones. RNA mutations that disrupted coat protein binding also prevented viral
      RNA replication without diminishing coat protein mRNA (RNA 4) translation. These
      results, coupled with the highly conserved nature of the AUGC865-868 sequence,
      suggest that the distance separating the two proposed hairpins is a critical
      binding determinant. The data may indicate that the 5' and 3' hairpins interact
      with one of the bound peptides to nucleate the observed RNA conformational
      changes.

PMID- 14681585
TI  - The 5'-3' exoribonuclease xrn-1 is essential for ventral epithelial enclosure
      during C. elegans embryogenesis.
AB  - Ribonucleases have been studied in yeast and bacteria, but their biological
      significance to multicellular organisms is virtually unknown. However, there is
      increasing evidence that specific, timed transcript degradation is critical for
      regulation of many cellular processes, including early development and RNA
      interference. In this report we have investigated the effects of the 5'-3'
      exoribonuclease xrn-1 on the development of the nematode worm Caenorhabditis
      elegans. Silencing of xrn-1 expression using RNA interference results in embryos
      that fail to complete ventral enclosure, where the outer layer of cells normally
      closes over the mesoderm in a purse-string movement. Our data suggest that xrn-1
      is involved in a critical aspect of epithelial movement and reveal an unexpected
      link between RNA stability and morphogenesis. Because xrn-1 is highly conserved
      in all eukaryotes, it is possible that it plays a role in similar morphological
      processes such as dorsal or thorax closure in Drosophila and wound healing in
      humans. In contrast to work in human tissue culture cells, where the 3'-5'
      pathway has been shown to be the most important for degradation of mRNAs, our
      work shows that the 5'-3' degradation pathway is crucially important at a
      critical stage of development in C. elegans. We have also investigated whether
      xrn-1 can influence the response of C. elegans to RNA interference. Our data
      indicate that xrn-1 plays a facilitating, but not crucial role in this process.

PMID- 14681586
TI  - Crystal structure of the BstDEAD N-terminal domain: a novel DEAD protein from
      Bacillus stearothermophilus.
AB  - Most cellular processes requiring RNA structure rearrangement necessitate the
      action of Asp-Glu-Ala-Asp (DEAD) proteins. Members of the family, named
      originally for the conserved DEAD amino acid sequence, are thought to disrupt RNA
      structure and facilitate its rearrangement by unwinding short stretches of duplex
      RNA. BstDEAD is a novel 436 amino acid representative of the DEAD protein family
      from Bacillus stearothermophilus that contains all eight conserved motifs found
      in DEAD proteins and is homologous with other members of the family. Here, we
      describe the 1.85 A resolution structure of the N-terminal domain (residues 1
      211) of BstDEAD (BstDEAD-NT). Similar to the corresponding domains of related
      helicases, BstDEAD-NT adopts a parallel alpha/beta structure with RecA-like
      topology. In general, the conserved motifs superimpose on closely related DEAD
      proteins and on more distantly related helicases such as RecA. This affirms the
      current belief that the core helicase domains, responsible for mechanistic
      activity, are structurally similar in DEAD proteins. In contrast, however, the so
      called Walker A P-loop, which binds the beta- and gamma-phosphates of ATP, adopts
      a rarely seen "closed" conformation that would sterically block ATP binding. The
      closed conformation may be indicative of a general regulatory feature among DEAD
      proteins (and RNA helicases) that differs from that used by DNA helicases.
      BstDEAD also contains a unique extension of approximately 60 residues at the C
      terminus that is highly basic, suggesting that it might bind nucleic acids and,
      in so doing, confer specificity to the helicase activity of the core region.

PMID- 14681587
TI  - Saccharomyces SRP RNA secondary structures: a conserved S-domain and extended Alu
      domain.
AB  - The contribution made by the RNA component of signal recognition particle (SRP)
      to its function in protein targeting is poorly understood. We have generated a
      complete secondary structure for Saccharomyces cerevisiae SRP RNA, scR1. The
      structure conforms to that of other eukaryotic SRP RNAs. It is rod-shaped with,
      at opposite ends, binding sites for proteins required for the SRP functions of
      signal sequence recognition (S-domain) and translational elongation arrest (Alu
      domain). Micrococcal nuclease digestion of purified S. cerevisiae SRP separated
      the S-domain of the RNA from the Alu-domain as a discrete fragment. The Alu
      domain resolved into several stable fragments indicating a compact structure.
      Comparison of scR1 with SRP RNAs of five yeast species related to S. cerevisiae
      revealed the S-domain to be the most conserved region of the RNA. Extending data
      from nuclease digestion with phylogenetic comparison, we built the secondary
      structure model for scR1. The Alu-domain contains large extensions, including a
      sequence with hallmarks of an expansion segment. Evolutionarily conserved bases
      are placed in the Alu- and S-domains as in other SRP RNAs, the exception being an
      unusual GU(4)A loop closing the helix onto which the signal sequence binding
      Srp54p assembles (domain IV). Surprisingly, several mutations within the
      predicted Srp54p binding site failed to disrupt SRP function in vivo. However,
      the strength of the Srp54p-scR1 and, to a lesser extent, Sec65p-scR1 interaction
      was decreased in these mutant particles. The availability of a secondary
      structure for scR1 will facilitate interpretation of data from genetic analysis
      of the RNA.

PMID- 14681588
TI  - Purine bases at position 37 of tRNA stabilize codon-anticodon interaction in the
      ribosomal A site by stacking and Mg2+-dependent interactions.
AB  - The anticodon loop of tRNA contains a number of conserved or semiconserved
      nucleotides. In most tRNAs, a highly modified purine is found at position 37
      immediately 3' to the anticodon. Here, we examined the role of the base at
      position 37 for tRNA(Phe) binding to the A site of Escherichia coli ribosomes.
      Affinities and rate constants of A-site binding of native yeast peptidyl
      tRNA(Phe) with hypermodified G (wybutine), or of unmodified peptidyl-tRNA(Phe)
      transcripts with G, A, C, or U, at position 37 were measured. The data indicate
      that purines stabilize binding due to stronger stacking and additional
      interactions with the ribosome mediated by Mg(2+) ions. Paromomycin, an
      antibiotic that binds to 16S rRNA in the decoding center, greatly stabilized
      tRNAs in the A site and abolished the Mg(2+)-dependence of binding. Comparison of
      binding enthalpies and entropies suggests that hypermodification of the base at
      position 37 does not affect stacking in the codon-anticodon complex, but rather
      decreases the entropic penalty for A-site binding. Substitution of purines with
      pyrimidines at position 37 increases the rates of tRNA binding to and
      dissociation from the A site. The data suggest that initial binding of tRNA to
      the A site is followed by a rate-limiting rearrangement of the anticodon loop or
      the ribosome decoding center that is favored by purines at position 37 and
      involves stronger stacking, additional Mg(2+) binding, and interactions with 16S
      rRNA.

PMID- 14681589
TI  - EF-G-independent reactivity of a pre-translocation-state ribosome complex with
      the aminoacyl tRNA substrate puromycin supports an intermediate (hybrid) state of
      tRNA binding.
AB  - Following peptide-bond formation, the mRNA:tRNA complex must be translocated
      within the ribosomal cavity before the next aminoacyl tRNA can be accommodated in
      the A site. Previous studies suggested that following peptide-bond formation and
      prior to EF-G recognition, the tRNAs occupy an intermediate (hybrid) state of
      binding where the acceptor ends of the tRNAs are shifted to their next sites of
      occupancy (the E and P sites) on the large ribosomal subunit, but where their
      anticodon ends (and associated mRNA) remain fixed in their prepeptidyl
      transferase binding states (the P and A sites) on the small subunit. Here we show
      that pre-translocation-state ribosomes carrying a dipeptidyl-tRNA substrate
      efficiently react with the minimal A-site substrate puromycin and that following
      this reaction, the pre-translocation-state bound deacylated tRNA:mRNA complex
      remains untranslocated. These data establish that pre-translocation-state
      ribosomes must sample or reside in an intermediate state of tRNA binding
      independent of the action of EF-G.

PMID- 14681590
TI  - In vitro selection of ribozymes dependent on peptides for activity.
AB  - A peptide-dependent ribozyme ligase (aptazyme ligase) has been selected from a
      random sequence population based on the small L1 ligase. The aptazyme ligase is
      activated > 18,000-fold by its cognate peptide effector, the HIV-1 Rev arginine
      rich motif (ARM), and specifically recognizes the Rev ARM relative to other
      peptides containing arginine-rich motifs. Moreover, the aptazyme ligase can
      preferentially recognize the Rev ARM in the context of the full-length HIV-1 Rev
      protein. The only cross-reactivity exhibited by the aptazyme is toward the Tat
      ARM. Reselection of peptide- and protein-dependent aptazymes from a partially
      randomized population yielded aptazymes that could readily discriminate against
      the Tat ARM. These results have important implications for the development of
      aptazymes that can be used in arrays for the detection and quantitation of
      multiple cellular proteins (proteome arrays).

PMID- 14681591
TI  - Sindbis virus nucleocapsid assembly: RNA folding promotes capsid protein
      dimerization.
AB  - In Sindbis virus, initiation of nucleocapsid core assembly begins with
      recognition of the encapsidation signal of the viral RNA genome by capsid
      protein. This nucleation event drives the recruitment of additional capsid
      proteins to fully encapsidate the genome, generating an icosahedral nucleocapsid
      core. The encapsidation signal of the Sindbis virus genomic RNA has previously
      been localized to a 132-nucleotide region of the genome within the coding region
      of the nsP1 protein, and the RNA-binding activity of the capsid was previously
      mapped to a central region of the capsid protein. It is unknown how capsid
      protein binding to encapsidation signal leads to ordered oligomerization of
      capsid protein and nucleocapsid core assembly. To address this question, we have
      developed a mobility shift assay to study this interaction. We have characterized
      a 32 amino acid peptide capable of recognizing the Sindbis virus encapsidation
      signal RNA. Using this peptide, we were able to observe a conformational change
      in the RNA induced by capsid protein binding. Binding is tight (K(d)(app) = 12
      nM), and results in dimerization of the capsid peptide. Mutational analysis
      reveals that although almost every predicted secondary structure within the
      encapsidation signal is required for efficient protein binding, the identities of
      the bases within the helices and hairpin turns of the RNA do not need to be
      maintained. In contrast, two purine-rich loops are essential for binding. From
      these data, we have developed a model in which the encapsidation signal RNA
      adopts a highly folded structure and this folding process directs early events in
      nucleocapsid assembly.

PMID- 14681593
TI  - Snowmobile fatalities--Maine, New Hampshire, and Vermont, 2002-2003.
AB  - During the 2002-2003 winter season in northern New England, 28 deaths in three
      states were associated with the use of snowmobiles, more than reported during any
      of the previous 12 winter seasons. The New Hampshire Department of Health and
      Human Services conducted a study to characterize these fatal injuries. This
      report describes the results of that study, which indicated that the leading
      contributors to snowmobile fatalities were excessive speed, inattentive or
      careless operation, and inexperience. Efforts to reduce snowmobile fatalities
      should focus on improving safety measures, including establishing speed limits,
      strengthening enforcement of snowmobile operating rules, and promoting safety
      education.

PMID- 14681592
TI  - Analysis of a long-range interaction between conserved domains of human
      telomerase RNA.
AB  - Telomerase is a ribonucleoprotein complex responsible for maintaining telomere
      length of eukaryotic chromosomes. Human telomerase has two main components, the
      human telomerase reverse transcriptase and the human telomerase RNA (hTR). Two
      domains of hTR essential for telomerase activity are the template domain,
      comprised of an 11-nt templating and alignment sequence, and the CR4/CR5 domain.
      Highly conserved residues in the CR4/CR5 domain form the stem-loop P6.1, which is
      important for assembly and activity of mammalian telomerase. Here, we have
      determined that stem-loop P6.1 can participate in a long-range RNA-RNA
      interaction with the template region of hTR. We characterized this interaction
      through mobility shift assays, mutation analysis, and UV cross-linking
      experiments. Mutation analysis revealed that the P6.1 loop nucleotides
      participate in the interaction with the template. The site of interaction at the
      template domain was determined via UV cross-linking experiments. These data show
      that an RNA-RNA interaction exists between two highly conserved regions of hTR
      that are critical for the higher order folding of telomerase RNA. This
      interaction argues for the proximity of the template and the CR4/CR5 domain, and
      provides the basis for a revised model of hTR, partitioning the RNA into a
      catalytic domain and a localization domain.

PMID- 14681594
TI  - Murine typhus--Hawaii, 2002.
AB  - Murine typhus, a zoonotic disease caused by Rickettsia typhi, is uncommon in the
      United States. Hawaii typically reports five or six cases annually; however, 47
      cases were reported in 2002. This report summarizes clinical data for three of
      these cases and describes murine typhus activity in Hawaii during 2002 and
      control efforts of the Hawaii Department of Health (HDH). The high number of
      reported cases in 2002 underscores the need for community education to prevent
      murine typhus and an assessment of environmental factors that might contribute to
      local disease transmission.

PMID- 14681595
TI  - Public health and aging: retention of natural teeth among older adults--United
      States, 2002.
AB  - During the past several decades, the percentage of older adults who have retained
      their natural teeth has increased steadily. This trend is expected to continue,
      resulting in improved oral function and quality of life. To estimate the
      prevalences of tooth retention and total tooth loss in 2002 among adults aged
      >/=65 years, CDC analyzed data from the Behavioral Risk Factor Surveillance
      System (BRFSS) survey. This report summarizes the results of that analysis, which
      indicated that in 26 (52%) states, more than half of older adults reported having
      most (i.e., losing five or fewer) of their natural teeth. However, rates varied
      substantially among states and by selected characteristics. With tooth retention,
      older adults remain at risk for dental caries (i.e., tooth decay) and periodontal
      disease. To help adults maintain healthy teeth for life, community-based
      strategies should promote healthy behaviors, optimal use of fluoride, timely
      examinations and clinical services, and increased research into preventing oral
      diseases and promoting oral health among adults.

PMID- 14681596
TI  - Internet use and early syphilis infection among men who have sex with men--San
      Francisco, California, 1999-2003.
AB  - During the summer of 1999, an outbreak of early syphilis among men who have sex
      with men (MSM) who met their sex partners on the Internet presaged a rapidly
      expanding syphilis epidemic in San Francisco. By 2002, San Francisco had the
      highest rates of primary and secondary syphilis of any metropolitan area in the
      United States. During 1998-2002, the number of early syphilis cases increased,
      from 41 cases in 1998 to 495 cases in 2002. Concomitant with the increase in
      early syphilis was an increase in the proportion of cases among MSM, from 22% in
      1998 to 88% in 2002. To assess the association between early syphilis infection
      and use of the Internet by MSM to meet sex partners, the San Francisco Department
      of Public Health (SFDPH) analyzed surveillance data and case reports. This report
      summarizes the results of that analysis, which suggest that public health
      officials might find the Internet to be an important tool for 1) promoting
      disease awareness, prevention, and control and 2) accessing sex partners of
      syphilis patients to conduct appropriate partner notification, evaluation, and
      management. The findings underscore the need for public health officials to
      understand the role of the Internet in facilitating the spread of sexually
      transmitted diseases (STDs), including the human immunodeficiency virus (HIV).
      With the assistance of community partners, other jurisdictions can examine the
      online social/sexual networks that are used commonly in their gay and bisexual
      communities and develop an effective means of communicating prevention and
      control messages online.

PMID- 14681597
TI  - Update: influenza activity--United States, December 7-13, 2003.
AB  - Influenza activity in the United States continued to increase during December 7
      13, 2003. The proportion of patient visits to sentinel providers for influenza
      like illness (ILI) overall was 7.4%, which is above the national baseline of
      2.5%. Thirty-six state health departments reported widespread influenza activity,
      12 states and New York City reported regional influenza activity, one state and
      the District of Columbia reported local influenza activity, and one state and
      Puerto Rico reported sporadic influenza activity

PMID- 14681598
TI  - Presidential address: Generations apart--bridging the generational divide in
      vascular surgery.

PMID- 14681599
TI  - Natural history of carotid artery stenosis contralateral to endarterectomy:
      results from two randomized prospective trials.
AB  - PURPOSE: A few nonrandomized studies have reported the natural history of carotid
      artery stenosis (CAS) contralateral to carotid endarterectomy (CEA). This study
      analyzed this condition with data from two randomized prospective trials.
      METHODS: The contralateral carotid arteries in 534 patients from two randomized
      trials that compared CEA with primary closure versus patching were followed up
      clinically and with duplex ultrasound scanning at 1 month and then every 6
      months. CAS was classified as less than 50%, 50% to 79%, 80% to 99%, and
      occlusion. Late contralateral CEA was performed to treat significant CAS.
      Progression was defined as progress to a higher category of stenosis. Kaplan
      Meier life table analysis was used to estimate freedom from progression of CAS.
      The correlation of risk factors and CAS progression was also analyzed. RESULTS:
      Of 534 patients, 61 had initial contralateral CEA and 53 had contralateral
      occlusion. Overall, CAS progressed in 109 of 420 patients (26%) at mean follow-up
      of 41 months. Progression of CAS was noted in 5 of 162 patients (3%) with
      baseline normal carotid arteries. CAS progressed in 56 of 157 patients (36%) with
      less than 50% stenosis versus 45 of 95 patients (47%) with 50% to 79% stenosis (P
      =.003). Median time to progression was 24 months for less than 50% CAS, and 12
      months for 50% to 79% CAS (P =.035). At 1, 2, 3, 4, and 5 years, freedom from
      disease progression in patients with baseline CAS <50% was 95%, 78%, 69%, 61%,
      48%, respectively, and in patients with 50% to 79% CAS was 75%, 61%, 51%, 43%,
      and 33%, respectively (P =.003). Freedom from progression in patients with
      baseline normal carotid arteries at 1 through 5 years was 99%, 98%, 96%, 96%, and
      94%, respectively. Late neurologic events referable to the CCA were infrequent
      (28 of 420 [6.7%] in the entire series; 28 of 258 [10.9%] patients with
      contralateral CAS), and included 10 strokes (2.4%) and 18 transient ischemic
      attacks (4.3%). However, late contralateral CEA was performed in 62 patients (62
      of 420 [15%] in the entire series; 62 of 258 [24%] patients with contralateral
      CAS). Survival rates were 96%, 92%, 90%, 87%, and 82%, respectively, at 1 through
      5 years. CONCLUSIONS: Progression of CCA stenosis was noted in a significant
      number of patients with baseline contralateral CAS. Serial clinical studies and
      duplex ultrasound scanning every 6 to 12 months in patients with 50% to 79% CAS,
      and every 12 to 24 months in patients with 50% or less CAS is adequate.

PMID- 14681601
TI  - In-stent recurrent stenosis after carotid artery stenting: life table analysis
      and clinical relevance.
AB  - OBJECTIVES: Carotid artery stenting has been proposed as an alternative to
      carotid endarterectomy in cerebral revascularization. Although early results from
      several centers have been encouraging, concerns remain regarding long-term
      durability of carotid artery stenting. We report the incidence, characteristics,
      and management of in-stent recurrent stenosis after long-term follow-up of
      carotid artery stenting. METHODS: Carotid artery stenting (n = 122) was performed
      in 118 patients between September 1996 and March 2003. Indications included
      recurrent stenosis after previous carotid endarterectomy (66%), primary lesions
      in patients at high-risk (29%), and previous ipsilateral cervical radiation
      therapy (5%). Fifty-five percent of patients had asymptomatic stenosis; 45% had
      symptomatic lesions. Each patient was followed up with serial duplex ultrasound
      scanning. Selective angiography and repeat intervention were performed when
      duplex ultrasound scans demonstrated 80% or greater in-stent recurrent stenosis.
      Data were prospectively recorded, and were statistically analyzed with the Kaplan
      Meier method and log-rank test. RESULTS: Carotid artery stenting was performed
      successfully in all cases, with the WallStent or Acculink carotid stent. Thirty
      day stroke and death rate was 3.3%, attributable to retinal infarction (n = 1),
      hemispheric stroke (n = 1), and death (n = 2). Over follow-up of 1 to 74 months
      (mean, 18.8 months), 22 patients had in-stent recurrent stenosis (40%-59%, n =
      11; 60%-79%, n = 6; > or =80%, n = 5), which occurred within 18 months of carotid
      artery stenting in 13 patients (60%). None of the patients with in-stent
      recurrent stenosis exhibited neurologic symptoms. Life table analysis and Kaplan
      Meier curves predicted cumulative in-stent recurrent stenosis 80% or greater in
      6.4% of patients at 60 months. Three of five in-stent recurrent stenoses occurred
      within 15 months of carotid artery stenting, and one each occurred at 20 and 47
      months, respectively. Repeat angioplasty was performed once in 3 patients and
      three times in 1 patient, and repeat stenting in 1 patient, without
      complications. One of these patients demonstrated asymptomatic internal carotid
      artery occlusion 1 year after repeat intervention. CONCLUSIONS: Carotid artery
      stenting can be performed with a low incidence of periprocedural complications.
      The cumulative incidence of clinically significant in-stent recurrent stenosis (>
      or =80%) over 5 years is low (6.4%). In-stent restenosis was not associated with
      neurologic symptoms in the 5 patients noted in this cohort. Most instances of in
      stent recurrent stenosis occur early after carotid artery stenting, and can be
      managed successfully with endovascular techniques.

PMID- 14681604
TI  - Acute arterial complications associated with total hip and knee arthroplasty.
AB  - OBJECTIVE: To our knowledge, ours is the largest single-center experience with
      diagnosis and management of acute arterial hemorrhagic and limb-threatening
      ischemic complications associated with total hip arthroplasty (THA) and total
      knee arthroplasty (TKA). METHODS: Between 1989 and 2002, 23,199 TKA procedures
      (13,618 total, 11,953 primary, 1665 revision) and THR procedures (9581 total,
      7812 primary, 1769 revision) were performed at the orthopedic service of
      Pennsylvania Hospital, Philadelphia. Arterial injuries were grouped according to
      type (ischemia, bleeding, pseudoaneurysm, ischemia plus bleeding) and time of
      recognition of injury (0-5 days after orthoplasty). RESULTS: Acute arterial
      complications developed in 32 patients (0.13%), associated with 24 TKA procedures
      (0.17%) and 8 THA procedures (0.08%; P =.0609). There were no deaths, and limb
      salvage was achieved in all patients. Arterial injury was detected by the
      orthopedic service on the same day (SD group) as performance of joint replacement
      in 18 patients (56%), but was not recognized until the first to fifth
      postoperative day (PO group) in 14 patients (44%). Arterial complications
      included acute lower-limb ischemia only in 18 patients SD group, 9; PO group, 9),
      bleeding only in 4 patients (SD group), arterial transection resulting in both
      ischemia and bleeding in 5 patients (SD group), and arterial pseudoaneurysm in 5
      patients (PO group). Of the 18 patients with acute ischemia only, preoperative
      arteriography was performed in 12 patients (67%), and 6 patients (33%) were
      brought directly to the operating room because of advanced ischemia.
      Revascularization procedures in these 18 patients included bypass to the
      infrapopliteal artery (n = 7), popliteal artery (n = 5), or common femoral artery
      (n = 1); in only 5 patients (28%) was thrombectomy alone successful. These 18
      patients tended to require fasciotomy (4 of 9 vs 2 of 9; P =.6199) and have foot
      drop (3 of 9 vs 1 of 9; P =.5765) more frequently when ischemia was recognized
      after the day of surgery. Bleeding was managed with arteriorrhaphy. Arterial
      transection was treated with end-to-end anastomosis (n = 3), interposition
      grafting (n = 1), and below-knee popliteal bypass (n = 1). Popliteal artery
      pseudoaneurysm was treated with percutaneous methods (n = 3) or surgery (n = 2).
      CONCLUSION: In this series, risk for arterial injury associated with THA and TKA
      was remarkably low. Nonetheless, even at a high-volume orthopedic hospital, acute
      arterial injury was not recognized on the day of surgery in about half of
      patients. Judicious use of preoperative arteriography and aggressive
      revascularization are critical to achieving limb salvage. Simple arterial
      thrombectomy to treat ischemic complications of THA and TKA is rarely sufficient.

PMID- 14681606
TI  - Efficacious use of nitinol stents in the femoral and popliteal arteries.
AB  - OBJECTIVE: To evaluate the performance and identify predictors of outcome after
      the use of self-expanding nitinol stents in the treatment of femoropopliteal
      arterial occlusive disease. METHODS: A retrospective analysis of a prospectively
      collected database was performed. Outcomes of patients who underwent placement of
      a nitinol stent in the femoral or above-knee popliteal arteries between 1999 and
      2002 were studied. Patency, limb salvage, and patient survival were determined by
      Kaplan-Meier estimation and intergroup comparisons by log-rank test and Cox
      proportional hazards model. To define individual factors associated with clinical
      outcomes, stepwise regression analysis was performed. RESULTS: A total of 41
      patients (mean age, 70 +/- 10 years; gender, 26 men and 15 women) underwent
      percutaneous placement of nitinol stents. Limb salvage was the indication for
      intervention in 68% of patients. Diabetes was present in 54%, and 36% had end
      stage renal disease. Nitinol stents were placed in the superficial femoral (35
      patients) or the above-knee popliteal (6 patients) arteries. The mean
      postprocedural increase in ankle-brachial index was 0.32 +/- 0.19. The 6-month, 1
      year, and 2-year primary patency and limb-salvage rates were 95%, 84%, and 84%,
      and 92%, 89%, and 89%, respectively. Major amputations occurred only in patients
      undergoing limb-salvage procedures presenting with major tissue loss. No
      statistically significant differences in patency were seen with regard to
      diabetes, end-stage renal disease, runoff score, length of vessel stented
      (median, 80 mm), hypertension, or smoking. CONCLUSIONS: Our initial experience
      with self-expanding nitinol stents for femoropopliteal occlusive disease appears
      to demonstrate acceptable patency and limb-salvage rates at these early time
      points. Further evaluation of clinical outcome with these devices in this and
      larger groups of patients is warranted.

PMID- 14681608
TI  - Thoracoabdominal aortic aneurysm repair after prior aortic surgery.
AB  - PURPOSE: The purpose of this study was to determine whether the morbidity and
      mortality of surgery for thoracoabdominal aortic aneurysm (TAAA) in patients with
      prior aortic surgery are increased. METHODS: The results for all patients
      undergoing operation for TAAA at a single institution were reviewed. RESULTS:
      Over a 10-year interval, 279 patients (136 women and 143 men) underwent aortic
      replacement for TAAA. The mean patient age was 68 years (range, 34-90). The
      extent of aortic replacement was relatively evenly distributed: type I (91), type
      II (54), type III (78), or type IV (56). Of these 279 patients, 76 (27%) had
      undergone prior aortic surgery. Prior infrarenal AAA was the most common prior
      procedure (56, 20%). Reoperation for prior failed TAAA repair was performed in 20
      (7%) patients. A history of Marfan syndrome was highly associated with the need
      for remedial TAAA procedures (P <.0001). Overall 30-day mortality was 11.4% (32).
      Mortality was independent of prior aortic surgery (P =.98), prior AAA (P =.84),
      prior TAAA (P =.61), and gender (P =.18). Postoperative complications were seen
      in 67 (24%) patients and were more likely in patients who had undergone prior AAA
      surgery (P =.008). TAAA repair in patients with recurrent TAAA was not associated
      with higher morbidity (P =.33). Paraplegia (10) occurred in type I (3), type II
      (2), and type III (5) aneurysms but not in type IV (0), and its development was
      associated with higher mortality (P =.01). Prior aortic surgery was not found to
      be predictive of paraplegia (P =.90), although 30% of patients who developed
      paraplegia had a history of prior AAA repair. CONCLUSIONS: Aortic reoperation for
      TAAA is required in a significant number of patients, particularly those with
      Marfan syndrome. Therefore, ongoing surveillance of the residual aorta is
      mandatory. Postoperative complications are more likely to occur in patients after
      prior infrarenal aortic replacement, but mortality is not significantly
      increased. Special technical considerations exist for remedial procedures after
      failed TAAA repair to provide protection for the spinal cord, kidneys, and
      viscera. Patients with failed TAAA procedures or progression of aneurysmal extent
      should be offered reoperation when indicated.

PMID- 14681610
TI  - Delayed open conversion following endovascular aortoiliac aneurysm repair:
      partial (or complete) endograft preservation as a useful adjunct.
AB  - OBJECTIVES: The purpose of this study was to review our experience with delayed
      open conversion (>30 days) following endovascular aortoiliac aneurysm repair
      (EVAR) and to introduce the concept and advantages of endograft retention in this
      setting. METHODS: From January 1992 to January 2003, a total of 386 EVARs using a
      variety of endografts were successfully deployed. Eleven (2.8%) patients required
      delayed conversion to open repair at an average of 30 months (range, 10-64). Data
      from all patients undergoing both EVAR and open conversion were prospectively
      collected. RESULTS: EVARs were performed using grafts made by Talent (4),
      Vanguard (2,) AneuRx (1), and Surgeon (4). Conversion to open repair (9
      transabdominal, 1 retroperitoneal, 1 transabdominal plus thoracotomy) was
      performed for aneurysm rupture in 7 patients (4 type 1 endoleak, 2 type 2
      endoleak, 1 aortoenteric fistula) and aneurysm enlargement in 4 patients (1 type
      1 endoleak, 1 type 2 endoleak, 1 type 3 endoleak, 1 endotension). Patients with
      aneurysm rupture were treated on an emergent basis. Complete removal of the
      endograft with supraceliac cross-clamping was performed in two cases. One patient
      (rupture) did not survive the operation, and one patient (aortoenteric fistula)
      died 2 weeks postoperatively. In the remaining nine cases, the endograft was
      either completely (1) or partially (6) removed, or left in situ (2). Supraceliac
      balloon control (2), supraceliac clamping (1), suprarenal clamping (1), or
      infrarenal clamping (5) was used in these cases. All nine of these patients
      survived the operation. In one procedure in which the endograft was left intact
      (endotension), repair was accomplished by exposing the endograft and by placing a
      standard tube graft over it as a sleeve. In the second procedure in which the
      graft was left in situ (rupture), the graft was well incorporated, and bleeding
      lumbar arteries were oversewn and the sac was closed tightly over the endograft.
      In the remaining 7 cases, the endograft was transected and the proximal portion
      only (6) or the proximal and distal portions (1) were excised. All surviving
      patients continue to do well and remain without complications associated with the
      endograft remnant at a mean follow-up of 22 months (range, 3-56) from the time of
      open conversion and 46 months (range, 10-73) from the time of original EVAR.
      CONCLUSIONS: Open repair in the setting of a long-standing endograft offers
      several unique technical challenges but can be successfully accomplished in most
      patients. Preservation of all or part of the endograft is possible in many
      patients. This technique simplifies the operative approach and is preferred over
      complete endograft removal if possible.

PMID- 14681612
TI  - Intra-abdominal aortic graft infection: complete or partial graft preservation in
      patients at very high risk.
AB  - BACKGROUND: Total graft excision with in situ or extra-anatomic revascularization
      is considered mandatory to treat infection involving the body of aortic grafts.
      We present a series of nine patients with this complication and such severe
      comorbid medical illnesses or markedly hostile abdomens that traditional
      treatments were precluded. In these patients selective complete or partial graft
      preservation was used. METHODS: Over the past 20 years we have treated nine
      infected infrarenal aortic prosthetic grafts with complete or partial graft
      preservation, because excision of the graft body was not feasible. In all nine
      patients infection of the main body of the aortic graft was documented at
      computed tomography or surgery. Essential adjuncts included percutaneous or
      operative drain placement into retroperitoneal abscess cavities and along the
      graft, with instillation of antibiotics three times daily, repeated debridement
      of infected groin wounds, and intravenous antibiotic therapy for at least 6
      weeks. RESULTS: One patient with purulent groin drainage treated with complete
      graft preservation died of sepsis. One patient with groin infection treated with
      complete graft preservation initially did well, but ultimately required total
      graft excision 5 months later, after clinical improvement. In four patients
      complete graft preservation was successful; two patients required excision of an
      occluded infected limb of the graft; and one patient underwent subtotal graft
      excision, leaving a graft remnant on the aorta, and axillopopliteal bypass. In
      summary, seven of nine patients survived hospitalization after complete or
      partial graft preservation; amputation was avoided in all but one patient; and no
      recurrent infection developed over mean follow-up of 7.6 years (range, 2-15
      years). CONCLUSIONS: Although contrary to conventional concepts, partial or
      complete graft preservation combined with aggressive drainage and groin wound
      debridement is an acceptable option for treatment of infection involving an
      entire aortic graft in selected patients with prohibitive risks for total graft
      excision. This treatment may be compatible with long-term survival and protracted
      absence of signs or symptoms of infection.

PMID- 14681616
TI  - Five-year results of a merger between vascular surgeons and interventional
      radiologists in a university medical center.
AB  - OBJECTIVES: We examined economic and practice trends after 5 years of a merger
      between vascular surgeons and interventional radiologists. METHODS: In 1998 a
      merger between the Division of Vascular Surgery and the Section of Interventional
      Radiology at the University of Rochester established the Center for Vascular
      Disease (CVD). Business activity was administered from the offices of the
      vascular surgeons. RESULTS: In 1998 the CVD included five vascular surgeons and
      three interventional radiologists, who generated a total income of $5,789,311 US
      dollars (34% from vascular surgeons, 24% from interventional radiologists, 42%
      from vascular laboratories). Vascular surgeon participation in endoluminal
      therapy was limited to repair of abdominal aortic aneurysms (AAAs). Income was
      derived from 1011 major vascular procedures, 10,510 catheter-based procedures in
      3286 patients, and 1 inpatient and 3 outpatient vascular laboratory tests. In
      2002 there were six vascular surgeons (five, full-time equivalent) and four
      interventional radiologists, and total income was $6,550,463 US dollars despite
      significant reductions in unit value reimbursement over the 5 years, a 4%
      reduction in the number of major vascular procedures, and a 13% reduction in
      income from vascular laboratories. In 2002 the number of endoluminal procedures
      increased to 16,026 in 7131 patients, and contributions to CVD income increased
      from 24% in 1998 to 31% in 2002. Three of the six vascular surgeons performed
      endoluminal procedures in 634 patients in 2002, compared with none in 1998.
      CONCLUSIONS: Gross revenues increased in a declining reimbursement and
      conventional practice environment, because of the increased number of endoluminal
      procedures, in part provided by vascular surgeons. The implications of these data
      should be considered by those responsible for training vascular surgeons.

PMID- 14681618
TI  - Carotid ultrasound findings as a predictor of long-term survival after abdominal
      aortic aneurysm repair: a 14-year prospective study.
AB  - PURPOSE: Several factors have been related to long-term survival after open
      abdominal aortic aneurysm (AAA) repair. The effect of carotid stenosis on outcome
      has not yet been examined. We performed an open prospective study to evaluate the
      prognostic significance of carotid stenosis on long-term survival of patients who
      had undergone elective operative repair of AAA. METHODS: Two hundred eight
      patients who underwent elective open AAA repair in our department between March
      1987 and December 2001 were included in the study. All patients were evaluated
      preoperatively with color duplex ultrasound (US) scanning of the carotid
      arteries, and were followed up with clinical examination and carotid duplex US
      scanning 1 month after the operation and every 6 months thereafter. Median
      duration of follow-up was 50 months (range, 5-181 months). Cardiovascular
      morbidity and mortality, as well as all causes of mortality, were recorded and
      analyzed with regard to traditional risk factors and carotid US findings.
      RESULTS: Twenty-seven fatal and 46 nonfatal cardiovascular events were recorded.
      Both univariate and multivariate analysis showed that carotid stenosis 50% or
      greater and echolucent plaque were significantly associated with cardiovascular
      mortality and morbidity. Carotid stenosis was a stronger predictor of
      cardiovascular death than was ankle/brachial index. Age, hypercholesterolemia,
      coronary artery disease, and diabetes mellitus were also associated with higher
      mortality and morbidity from cardiovascular causes. CONCLUSION: Patients
      electively operated on for AAA repair and with stenosis 50% or greater and
      echolucent plaque at duplex US scanning are at significantly increased risk for
      cardiovascular mortality and morbidity. Carotid US can therefore be used to
      select a subgroup of patients with AAA who might benefit from medical
      intervention, including antiplatelet and lipid-lowering agents.

PMID- 14681614
TI  - Durability and cumulative functional patency of transposed and nontransposed
      arteriovenous fistulas.
AB  - OBJECTIVES: Preoperative duplex scanning of arm and forearm veins has increased
      the creation of autogenous arteriovenous (AV) fistulas. However, the cumulative
      functional patency and durability of transposed AV fistulas (TAVF) compared with
      nontransposed AV fistulas (AVF) and prosthetic bridging grafts (AVG) remains ill
      defined. METHODS: From January 1998 to December 2002, 245 dialysis access
      procedures were performed at University Hospital and the Veteran Affairs Medical
      Center in New Jersey. Follow-up data were available for 125 procedures (TAVF, n =
      42; AVF, n = 30; AVG, n = 53) performed in 97 patients. All access procedures
      were planned on the basis of preoperative duplex scans of arm and forearm veins.
      Functional patency was defined as ability to cannulate and hemodialyze patients
      successfully. Primary and secondary cumulative functional patency of TAVFs, AVFs,
      and AVGs was determined with life table analysis, and differences were analyzed
      with the log-rank test. Differences in revision rates, including thrombolysis,
      thrombectomies, and operative revisions, were determined with the Fisher exact t
      test. RESULTS: Mean follow-up was 18 months (range, 4-24 months). For TAVFs,
      AVFs, and AVGs, primary functional patency rate at 1 year was 76.2%, 53.3%, and
      47.2%, respectively, and at 2 years was 67.7%, 34.4%, and 25.5%, respectively.
      Similarly, secondary functional patency rate at 1 year was 83.2%, 66.7%, and
      58.5%, respectively, and at 2 years was 74.6%, 56.2%, and 40.2%, respectively.
      Primary and secondary functional patency rates for TAVFs were superior to those
      for AVGs at 1 and 2 years (P <.001). AVFs had superior secondary functional
      patency rate at 2 years, compared with AVGs (P <.05), and TAVFs had superior
      primary and secondary patency rates at 2 years, compared with AVFs (P <.05). AVGs
      required significantly more revisions than did TAVFs (28.5% vs 54.7%; P <.001) or
      AVFs (36.7% vs 54.7%; P <.05). CONCLUSIONS: Preoperative duplex scanning of upper
      arm and forearm veins facilitated successful creation of all types of autogenous
      fistulas at our institution. TAVF cumulative functional patency rates were
      superior compared with AVGs and AVFs. Furthermore, TAVFs and AVFs were more
      durable and required fewer revisions than did AVGs. When preoperative duplex
      criteria indicate that TAVFs can be performed, they should be the initial access
      of choice, because of their superior long-term patency and durability.

PMID- 14681619
TI  - Patients' thromboembolic potential after carotid endarterectomy is related to the
      platelets' sensitivity to adenosine diphosphate.
AB  - Background and purpose Postoperative microemboli in patients undergoing carotid
      endarterectomy are a significant risk factor for stroke. These emboli can be
      detected by intraoperative transcranial Doppler monitoring. They are not linked
      to technical error and are variable between patients. As it is known that
      platelets play a key role in arterial thrombosis, it was hypothesized that a
      patient's risk of postoperative carotid thrombosis was linked to the individual's
      platelet response to physiologic agonists. METHODS: Blood samples from 120
      patients undergoing carotid endarterectomy were analyzed before surgery. Platelet
      aggregation was measured in response to adenosine diphosphate (ADP) (0.5 to 4
      micromol/L), collagen (10 to 50 mg/mL), and arachidonic acid (3 or 6 micromol/L),
      and fibrinogen binding to GPIIb-IIIa was measured by whole blood flow cytometry
      in response to ADP (0.1 to 10 micromol/L) and thrombin (0.02 to 0.16 micro/mL).
      Patients underwent intraoperative transcranial Doppler monitoring for 3 hours
      after surgery, and platelet functional data of those who had >25 emboli in this
      period (n = 22) were compared with the data of those with <25 emboli (n = 88).
      RESULTS: The platelet response to ADP was significantly higher in the patients
      with >25 emboli, as measured both by aggregometry (P =.0012) and by flow
      cytometry (P <.0001). Platelet aggregation with collagen was also significantly
      higher in this group (P =.0018), but the response to thrombin was not
      statistically different in the two groups. In addition, there was no difference
      in the response to arachidonic acid between the groups. CONCLUSION: The platelet
      response to ADP may be linked to clinical outcome, and thus, specific ADP
      receptor inhibitors may be appropriate for this group of patients.

PMID- 14681620
TI  - Prospective, randomized study of external jugular vein patch versus
      polytetrafluoroethylene patch during carotid endarterectomy: perioperative and
      long-term results.
AB  - OBJECTIVES: The purpose of this study was to evaluate the relative risks and
      advantages of using external jugular vein (EJV) patch, compared with
      polytetrafluoroethylene (PTFE) patch, during carotid endarterectomy. The primary
      end point was the relevant neurologic complication rate (RNCR; fatal or disabling
      stroke) at any time during follow-up. Secondary end points included stroke-free
      survival, 30-day and long-term mortality, recurrent stenosis rate (> or =50%),
      occlusion, patch infection, aneurysm formation, and other local complications.
      METHODS: The study, a prospective randomized clinical trial carried out at a
      single center, was divided into two 3-year phases: December 1996 to March 1999,
      when patients were enrolled, and March 1999 to March 2002, which was the follow
      up period. Inclusion criteria included an external jugular vein suitable for
      patching, defined as vein diameter 3 mm or larger and absence of collateral
      vessels noted on preoperative color duplex ultrasound scans. Patients were
      prospectively randomized 1:1 to receive either the EJV (n = 80; group A) or
      synthetic (n = 80; group B) patch. RESULTS: Carotid endarterectomy and patching
      was performed by one surgeon. At 30 months the RNCR-free rate, analyzed with the
      Kaplan-Meier method, was 98.7% for group A (1 ipsilateral lethal stroke) and
      94.6% for group B (4 ipsilateral disabling strokes), and remained stable to 60
      months. No statistical difference was observed with the log-rank test. Stroke
      free survival rate was 100% for group A and 98.7% for group B at 1 year, 98.7%
      for group A and 93.6% for group B (1 ipsilateral minor stroke) at 30 months, and
      was unchanged at 60 months. Life table analysis demonstrated freedom from
      significant recurrent stenosis (> or =50%) of 97.5% for both groups at 6 months,
      93.6% for group A and 92.2% for group B at 30 months, and 90.2% for group A and
      86.7% for group B at 60 months. No statistical difference was observed with the
      log-rank test. In no patients was recurrent stenosis greater than 70%. No
      aneurysm formation was noted during follow-up. CONCLUSIONS: We can conclude, with
      the power limitation of the study, that carotid endarterectomy can be safely
      performed with either the EJV or PTFE patch. Advantages of the EJV for carotid
      angioplasty include no cost for material, low risk for graft infection, and
      preservation of the saphenous vein.

PMID- 14681621
TI  - Atherosclerotic plaque rupture and intraplaque hemorrhage do not correlate with
      symptoms in carotid artery stenosis.
AB  - OBJECTIVE: Previously we failed to demonstrate a correlation between plaque type
      and symptoms in 165 carotid endarterectomy specimens. The purpose of this study
      was to analyze the relation between the anatomy of the carotid plaques and the
      presence of symptoms in 281 carotid endarterectomy specimens. METHODS: The
      patients were 213 men (mean age, 68 years) and 68 women (mean age, 68.7 years),
      with symptomatic disease (n = 133) or asymptomatic disease (n = 148). Specimens
      were processed for histologic analysis and immunohistochemistry. RESULTS: Plaques
      were categorized as complicated or noncomplicated, and ruptured or nonruptured.
      Risk factors could not be correlated with any pathologic or immunohistochemical
      findings or between plaque type and clinical symptoms. CONCLUSIONS: Almost 70% of
      plaque specimens demonstrated thrombus, intraplaque hemorrhage, or both.
      Thrombosis was observed in one fourth of specimens, and intraplaque hemorrhage in
      almost two thirds of specimens. Sixty four percent of plaques demonstrated
      neovascularization. It was not possible to demonstrate that complicated plaques
      (plaque rupture, thrombosis, intraplaque hemorrhage) are associated with
      symptoms, and it appears that such plaques may occur at any time, irrespective of
      symptoms.

PMID- 14681622
TI  - Cognitive performance in patients after carotid endarterectomy.
AB  - OBJECTIVE: Research investigating the benefits of carotid endarterectomy (CEA) on
      cognitive functioning remains inconclusive. This study sought to determine what
      patient characteristics affect cognitive functioning and whether changes in
      cognitive functioning occur following surgery after controlling for these
      characteristics. METHODS: In a prospective longitudinal study, 39 patients
      scheduled for CEA surgery underwent neuropsychological testing in the week prior
      to their surgery. Two patients had a stroke following surgery, leaving 37
      patients who were tested again at 7 days and 3 months following surgery. The
      surgery was performed under a locoregional anesthetic. RESULTS: Patient
      characteristics associated with cognitive functioning were age, education, and
      IQ. In addition, differences in cognitive performance on a number of tests were
      related to presenting symptoms. Stroke patients (n = 6) differed significantly
      from symptom-free patients (n = 18) and patients with symptoms (n = 13) on
      measures of verbal fluency, visual search and mental flexibility, and verbal
      learning. When differences in patient characteristics were controlled for, no
      significant changes in cognitive functioning were found that could be attributed
      to the effects of surgery. CONCLUSIONS: No changes in cognitive functioning were
      associated with CEA. Differences in cognitive functioning, however, were
      associated with patient characteristics, including differences in presenting
      symptoms.

PMID- 14681624
TI  - Volume regression of abdominal aortic aneurysms and its relation to successful
      endoluminal exclusion.
AB  - OBJECTIVES: Evaluating the success of endoluminal repair of abdominal aortic
      aneurysms (AAAs) is frequently based on diameter measurements and determining the
      presence of endoleaks. The use of three-dimensional volumetric data and
      observation of morphologic changes in the aneurysm and device have been proposed
      to be more appropriate for postdeployment surveillance. The purpose of this study
      was to analyze the long-term volumetric and morphologic data of 161 patients who
      underwent endovascular AAA exclusion and to assess the utility of volume
      measurements for determining successful AAA repair. METHODS: Patients with spiral
      computed tomography scans obtained preoperatively, within the first postoperative
      month, at 6 months, and annually thereafter, were included in this analysis.
      Computerized interactive three-dimensional reconstruction of each AAA scan was
      performed. Total aneurysm sac volume was measured at each time interval (mean
      preoperative volume 169.0 +/- 78.5 mL), and the significance of volume changes
      was determined by mixed linear modeling, a form of repeated measures analysis, to
      account for longitudinal data clustered at the individual level. Sixty-two
      patients (38%) developed endoleaks at some time during follow-up-15 type I leaks,
      45 type II leaks, and 2 type III leaks. The patients with type I and type III
      leaks were treated with cuffs, and the type II leaks were treated either with
      observation, side-branch embolization, or required open conversion. RESULTS:
      Aneurysm sac volume increased slightly at 1-month follow-up (+3.3%), and then
      decreased steadily to -12.9% at 5 years (P <.0001). This effect remained
      unchanged after controlling for the three device types used in our study
      population. Patients who did not exhibit an endoleak (n = 99) showed a
      significant decrease in aneurysm volume across the entire follow-up duration when
      compared with those who did exhibit an endoleak (n = 62) (P <.0001). The presence
      of a 10% or greater decrease in volume at 6 months demonstrated a sensitivity of
      64%, a specificity of 95%, a positive predictive value of 95%, a negative
      predictive value of 62%, and an accuracy of 75% for predicting primary clinical
      success defined by successful deployment of the device; freedom from aneurysm- or
      procedure-related death; freedom from endoleak, rupture, migration, or device
      malfunction; or conversion to open repair. CONCLUSIONS: Volumetric analysis may
      be used to predict successful endoluminal exclusion of AAAs. Volume regression
      appears to be device-independent and should be expected in most clinically
      successful cases. The presence of volume increases in the first 6 months is
      suspicious for an endoleak that is pressurizing the aneurysm sac and heralds the
      need for closer evaluation and possible intervention. A volume decrease of 10% or
      greater at 6 months and continuing regression over time is associated with
      successful endovascular repair.

PMID- 14681625
TI  - Stent graft migration after endovascular aneurysm repair: importance of proximal
      fixation.
AB  - OBJECTIVE: We reviewed the incidence of stent-graft migration after endovascular
      aneurysm repair in a prospective multicenter trial and identified factors that
      may predispose to such migration. METHODS: All patients who received treatment
      during the course of the multicenter AneuRx clinical trial were reviewed for
      evidence of stent-graft migration over 5 years, from 1996 to 2001. Post
      deployment distance from the renal arteries to the proximal end of the stent
      graft and the proximal fixation length (length of the infrarenal neck covered by
      the stent graft) were determined in patients for whom pre-procedure and post
      procedure computed tomography scans were measured in an independent core
      laboratory. RESULTS: Stent-graft migration was reported in 94 of 1119 patients,
      with mean time after device implantation of 30 +/- 11 months. Freedom from
      migration was 98.6% at 1 year, 93.4% at 2 years, and 81.2% at 3 years (Kaplan
      Meier method). Subset (n = 387) analysis revealed that initial device deployment
      was lower in 47 patients with migration, as evidenced by a greater renal artery
      to stent-graft distance (1.1 +/- 0.7 cm), compared with 340 patients without
      migration (0.8 +/- 0.6 cm; P =.006) on post-implantation computed tomography
      scan. Proximal fixation length was shorter in patients with migration (1.6 +/-
      1.4 cm) compared with patients without migration (2.3 +/- 1.4 cm; P =.005). There
      was significant variation in migration rate among clinical sites (P <.001),
      ranging from 0% to 30% (median, 8%), with a greater than twofold difference in
      migration rate between the lowest quartile (6%) and the highest quartile (15%)
      clinical sites. Univariate and multivariate analysis revealed that renal artery
      to stent-graft distance (P =.001) and proximal fixation length (P =.005) were
      significant predictors of migration, and that each millimeter increase in
      distance below the renal arteries increased risk for subsequent migration by 5.8%
      and each millimeter increase in proximal fixation length decreased risk for
      migration by 2.5%. Pre-implantation aortic neck length, neck diameter, degree of
      device oversizing, correct versus incorrect oversizing, device type (stiff vs
      flexible), placement of proximal extender cuffs at the original procedure, and
      post-procedure endoleak were not significant predictors of migration. Migration
      was treated with placement of extender modules in 23 patients and surgical
      conversion in 7 patients; 64 patients (68%) with migration have required no
      treatment. CONCLUSIONS: Stent-graft migration among patients treated in the
      AneuRx clinical trial appears to be largely related to low initial deployment of
      the device, below the renal arteries, and short proximal fixation length.
      Significant variation in migration rate among clinical sites highlights the
      importance of the technical aspects of stent-graft deployment. Advances in
      intraoperative imaging and deployment techniques that have been made since
      completion of the clinical trial facilitate precision of device placement below
      the renal arteries and should increase proximal fixation length. Whether this,
      together with increased iliac fixation length, will result in lower risk for
      migration remains to be determined in long-term follow-up studies.

PMID- 14681627
TI  - Use of abdominal aortic endovascular prostheses in France from 1999 to 2001.
AB  - BACKGROUND: Since the introduction of endovascular repair (EVR) for infrarenal
      abdominal aortic aneurysm (AAA), clinical evaluation has been under way in many
      countries throughout the world. The main purpose of this retrospective study was
      to determine outcome of EVR with aortic endovascular prostheses (AEPs) and to
      evaluate the extent to which French practitioners have complied with regulatory
      and clinical guidelines for the use of these trial devices. METHODS: This
      retrospective study was conducted by the French National Health Insurance Fund
      for Salaried Workers. Data were compiled on EVR procedures performed at health
      care institutions all over mainland France between June 1999 and May 2001.
      RESULTS: A total of 1012 AEPs were deployed for AAA repair in France during the
      study period. Only 151 (14.9%) of these EVR procedures were carried out within an
      approved investigational setting with informed patient consent. Only 149 of the
      861 patients (17.3%, 95% confidence interval [CI], 14.9 to 19.9%) who underwent
      endovascular repair in noninvestigational settings signed informed consent forms.
      In 452 cases (46.5%), the diameter of the AAA was 50 mm or less. Complete outcome
      data for the first year were available for 891 patients (88%). Complications
      occurred in 177 of these patients (19.9%, 95% CI, 17.3 to 22.6%). There were a
      total of 47 deaths (5.3%, 95% CI, 3.9 to 6.9%), including 27 during the first 30
      postoperative days. Other major events during the first year after AEP
      implantation were ruptured AAA in 5 patients, conversion to open operation in 15,
      and additional endovascular treatment in 52. Data on clinical surveillance were
      available for 987 patients (97.5%) with a mean follow-up of 345 days. Only 294
      patients (29.8%, 95% CI, 27.0 to 32.7%) underwent complete imaging within the
      first month after AEP implantation. A total of 184 patients (18.6%, 95% CI, 16.3
      to 21.2%) received no surveillance at all. CONCLUSION: This study shows the need
      for improvement in the clinical evaluation of new devices and medical
      technologies in France. Study findings also confirm the significant incidence of
      adverse outcomes and necessity for routine surveillance after EVR of AAA with
      AEP. However, risk/benefit analysis is difficult because most procedures were not
      carried out within a proper investigational context.

PMID- 14681629
TI  - Influence of intraluminal thrombus on structural and cellular composition of
      abdominal aortic aneurysm wall.
AB  - INTRODUCTION: It has been suggested that the intraluminal thrombus of abdominal
      aortic aneurysm (AAA) affects the underlying vessel wall. Aneurysm enlargement
      has been associated with growth of thrombus, and rupture has been proposed to
      occur after bleeding into the thrombus. To examine how thrombus affects the
      vessel wall, we compared the morphology of aneurysm wall covered with thrombus
      with wall segments exposed to flowing blood. Material and methods Sixteen
      patients (14 men, 2 women; age range, 56-79 years) undergoing elective repair of
      AAA, where computed tomography scans showed thrombus and segments of the aneurysm
      wall exposed to flowing blood, were included in the study. Specimens from the
      aneurysm were taken for light and electron microscopy. Masson trichrome staining
      was performed for wall thickness determination and demonstration of collagen, and
      Weigert-van Gieson staining for elastin. The cellular composition was analyzed by
      immunohistochemistry with antibodies against CD3 for T cells, CD4 for T helper
      cells, CD8 for T cytotoxic cells, CD20 for B cells, CD68 for macrophages, and
      smooth muscle alpha-actin for smooth muscle cells (SMCs). Caspase-3 staining and
      TUNEL analysis were performed to evaluate apoptosis. RESULTS: The aneurysm wall
      covered with thrombus was thinner and contained fewer elastin fibers, and the few
      that were found were often fragmented. This part of the wall also contained fewer
      SMCs and more apoptotic nuclei than the wall exposed to flowing blood. Clusters
      of inflammatory cells were detected in the media of the aneurysm wall and in
      higher numbers in the parts covered with thrombus. Electron microscopy showed
      that the aneurysm wall without thrombus contained a dense collagenous matrix with
      differentiated SMCs. In the segment covered with thrombus, SMCs were more
      dedifferentiated (synthetic) and apoptotic or necrotic. There were also an
      increased number of inflammatory cells located in close contact with SMCs in
      various stages of apoptosis. CONCLUSION: The aneurysm wall covered with thrombus
      is thinner and shows more frequent signs of inflammation, apoptosis of SMCs, and
      degraded extracellular matrix. These findings suggest that thrombus formation and
      accumulation of inflammatory cells may perturb the structural integrity and
      stability of the vessel wall and thereby increase the risk for aneurysm rupture.

PMID- 14681630
TI  - Transbrachial arterial insertion of aortic occlusion balloon catheter in patients
      with shock from ruptured abdominal aortic aneurysm.
AB  - OBJECTIVE: Of 125 surgical patients with abdominal aortic aneurysm (AAA) treated
      from 1999, 11 patients with deep shock from ruptured AAAs who underwent aortic
      occlusion balloon catheter (AOBC) insertion before laparotomy were studied.
      METHODS: With the patients under local anesthesia, the brachial artery was
      exposed and the balloon catheter was inserted into the thoracic aorta. The
      balloon was inflated halfway and pulled back gently to the orifice of the left
      subclavian artery, and was advanced with the aid of blood flow down to the
      abdominal aorta. After full inflation of the balloon, the catheter was pulled
      until the balloon was fixed at the proximal shoulder of the AAA. RESULTS: AOBC
      insertion was completed within 16.1 +/- 5.1 minutes. Systolic blood pressure at
      presentation was 84.1 +/- 31.7 mm Hg, deteriorated to 60.9 +/- 15.4 mm Hg on
      arrival in the operating room, and increased significantly (P <.0001) to 123.4 +/
      25.3 mm Hg after AOBC insertion. The balloon burst in three patients. Embolic
      complications were observed in two patients. There were three deaths, two
      associated with the balloon bursting. In nine patients whose shock was
      successfully controlled by AOBC, operative mortality was 11%. CONCLUSION:
      Transbrachial arterial insertion of an AOBC may be useful to ameliorate
      hemorrhagic shock in patients with ruptured AAAs.

PMID- 14681631
TI  - Remote iliac artery endarterectomy: seven-year results of a less invasive
      technique for iliac artery occlusive disease.
AB  - OBJECTIVE: Remote endarterectomy of external and common iliac artery occlusions
      through a single, groin incision under fluoroscopic guidance is a relative
      unknown surgical procedure. This prospective single center cohort study describes
      this less invasive endovascular technique with the ring strip cutter and its
      early complications. The results at midterm follow-up are presented. PATIENTS AND
      METHODS: From April 1994 to July 2001, 49 remote-endarterectomies of the external
      or common iliac artery were performed in a retrograde manner from a single, groin
      incision in 48 patients (30 men, 31 procedures). The median age was 66 years (39
      to 82 years). Indications for operation were as follows: severe claudication in
      28 (57%), rest pain in 13 (27%), and gangrene in 8 (16%) procedures. Follow-up
      included clinical evaluation, ankle-brachial index, and duplex scanning at 6
      weeks, 3 months, and yearly thereafter. RESULTS: Intraoperative technical success
      was achieved in 43 (88%) procedures. A retroperitoneal incision was necessary in
      three patients for an additional arteriotomy in the iliac artery and in three
      others for a bypass procedure. The mean follow-up was 20 months (2 to 77 months).
      Three-year cumulative primary patency rate by means of life table analysis was
      60.2% +/- 12.0 (SE). During follow-up, percutaneous transluminal balloon
      angioplasty with and without stenting was performed in six and two patients,
      respectively, resulting in a 3-year primary-assisted patency rate of 85.7% +/-
      9.56. Three-year secondary patency was 94.2% +/- 5.50. CONCLUSIONS: Remote
      endarterectomy in external and common iliac arterial occlusive disease is a
      feasible endovascular procedure with a low complication rate. The midterm primary
      assisted patency rate is good.

PMID- 14681632
TI  - Can the Perclose suture-mediated closure system be used safely in patients
      undergoing diagnostic and therapeutic angiography to treat chronic lower
      extremity ischemia?
AB  - PURPOSE: Mechanical closure devices for arterial hemostasis after angiography,
      such as the Perclose suture-mediated closure system, are designed to decrease
      time to ambulation and improve patient comfort. Although these devices are safe
      and efficacious, to date there has been little reported about use of the Perclose
      device in a cohort consisting exclusively of patients with lower extremity
      peripheral vascular disease. The purpose of this study was to determine the
      safety and efficacy of routine use of the Perclose system in patients with
      documented peripheral vascular disease undergoing angiography to treat chronic
      lower extremity ischemia. METHODS: The Perclose device was placed for arterial
      closure after femoral artery access in 500 consecutive patients with documented
      peripheral vascular disease (ankle-brachial index, <0.8) who underwent diagnostic
      angiography or percutaneous intervention because of chronic lower extremity
      ischemia. These 500 patients composed 91% of all patients who underwent
      angiography because of chronic lower extremity ischemia between January 1, 2001,
      and April 1, 2002. All complications associated with the Perclose device were
      identified and reviewed. RESULTS: Of the 500 arteries, 54% were accessed for
      diagnostic angiography and 46% for intervention. Perclose device placement was
      successful in 475 attempts (95%). Overall major complication rate was 1.4% (7 of
      500 arteries). Complications included one death from retroperitoneal hemorrhage;
      three episodes of limb ischemia, two requiring operation and one requiring lytic
      therapy; two pseudoaneurysms; and one hematoma, which prolonged hospitalization.
      The hematoma was the only complication in the 25 patients with failed Perclose
      device placement. There were no infections requiring admission or operation.
      CONCLUSION: The Perclose suture-mediated closure device is efficacious and can be
      used safely in selected patients with documented peripheral vascular disease.
      Complications associated with this device tend to be more severe than those
      historically reported for manual compression. Substantial experience with use of
      this device is required to achieve excellent results in patients with difficult
      anatomy.

PMID- 14681633
TI  - Noninvasive augmentation of microvessel number in patients with peripheral
      vascular disease.
AB  - OBJECTIVE: Therapeutic angiogenesis has great potential for the treatment of
      ischemic diseases. One possible route for noninvasive induction of microvessels
      has recently been suggested by the finding that subcontractile electrical
      stimulation induces increased vascularization in animals. The present study tests
      the ability of such stimulation to augment microvessel number in patients with
      peripheral vascular disease. DESIGN OF STUDY: Overall, 36 patients were randomly
      assigned to control (n = 12) and treatment (n = 24) groups. Patients in the
      treatment group received localized subcontractile electrical stimulation on the
      feet of their ischemic limbs for three 60-minute periods each day over a 6-week
      period. Microvessel density was determined by capillary microscopy before
      treatment, at 3 and 6 weeks during treatment, and 4 weeks after completion.
      Transcutaneous oxygen tension was also determined at this site. RESULTS:
      Microvessel density determined by capillary microscopy was significantly
      increased (1.25-fold, P <.005) during and after treatment in patients receiving
      electrical stimulation. Transcutaneous oxygen tension was similarly increased in
      the treated patients (1.24-fold, P <.05). No changes were observed in these
      parameters in untreated patients examined in parallel. CONCLUSION: Localized
      subcontractile electrical stimulation can increase microvessel density and tissue
      perfusion in patients with peripheral vascular disease.

PMID- 14681634
TI  - Upper extremity bypass grafting for limb salvage in end-stage renal failure.
AB  - OBJECTIVE: Patients with end-stage renal failure and upper-extremity arterial
      occlusive disease sometimes have painful digital ulceration. We evaluated the
      efficacy of distal bypass grafting from the brachial artery for limb salvage in
      this setting. METHODS: All patients with end-stage renal disease with painful
      digital ulceration or gangrene of the hand seen from 1992 to 2002 were evaluated
      with clinical examination and noninvasive studies. Those with evidence of
      occlusive disease underwent conventional angiography. Individuals with forearm
      occlusive disease underwent bypass grafting, from the brachial artery to either
      the distal radial artery or ulnar artery at the level of the wrist or proximal
      hand. Follow-up was scheduled at regular intervals, and included duplex scanning.
      Limb salvage and bypass graft patency were determined with life table analysis.
      RESULTS: Over 10 years, 18 forearm bypass procedures were performed in 15
      patients. The outflow artery was the radial artery in 15 procedures and the ulnar
      artery in 3 procedures. Bypass conduit was autogenous in all patients. No patient
      had a functioning arteriovenous fistula at bypass grafting; six limbs had
      previously occluded fistulas. Two bypass grafts (11%) occluded in the early
      postoperative period, with resultant progression of gangrene. In the remaining 16
      grafts patency was maintained (mean follow-up, 18 months), with pain control and
      tissue healing. CONCLUSION: Treatment in patients with renal failure with upper
      extremity occlusive disease may be facilitated with brachiodistal bypass
      grafting. Pain control and reversal of progression of hand necrosis can be
      achieved.

PMID- 14681635
TI  - Heparin-induced thrombocytopenia: twenty-nine years later.
AB  - OBJECTIVE: To determine the current frequency, types of patients, indications for
      testing, morbidity and mortality, and management of heparin-induced
      thrombocytopenia (HIT). METHODS: Between December 1998 and July 2001, the charts
      of 102 inpatients that tested positive for heparin-associated antiplatelet
      antibodies (HAAb) were reviewed. There were 33,941 inpatients, 10,348 of them
      having received unfractionated or low molecular weight heparins. HAAb were
      determined by platelet aggregometry. RESULTS: There were 58 males and 44 females
      with a mean age of 56 years. The majority (72%) of patients were admitted to a
      surgical service (23% were admitted to medicine, and 5% were admitted to
      obstetrics/pediatrics). Indications for testing included one or more low platelet
      counts (n = 51), unexplained arterial (n = 33) or venous (n = 6) thromboses,
      resistance to anticoagulation (n = 1), prior history of HAAb (n = 3), organ
      transplant (n = 17), or other indication (n = 4). The HAAb "patterns" were
      variable, with patients having antibodies only to bovine (n = 7) or porcine
      heparin (n = 5), bovine and porcine heparins (n = 17), enoxaparin (n = 3),
      fragmin (n = 7), or all 4 heparins (n = 43). The HIT-related mortality was 6.9%,
      and the morbidity was 30% with 19 arterial and 7 venous thromboses and 5 bleeding
      events. Management consisted of discontinuation of heparin in 95 patients. Twenty
      five patients did not require continued anticoagulation. When needed,
      anticoagulation was continued with a direct thrombin inhibitor (n = 32),
      enoxaparin (n = 16), warfarin (n = 15), or aspirin (n = 7). Seven patients
      continued to receive unfractionated heparin (n = 4) or low molecular weight
      heparin (n = 3). CONCLUSIONS: HIT occurs in 0.99% of inpatients receiving heparin
      and remains an important nondiscriminatory contributor to their morbidity and
      mortality. Patients receiving any form of heparin who develop a decreasing
      platelet count, unexplained thrombosis, or resistance to heparin anticoagulation
      should be tested for HAAb. If HAAb are detected, patients must not receive the
      sensitizing heparin(s).

PMID- 14681636
TI  - Changes in ankle brachial index in symptomatic and asymptomatic subjects in the
      general population.
AB  - OBJECTIVE: To determine changes over time in the ankle brachial index (ABI) among
      subjects with and without intermittent claudication in the general population.
      DESIGN OF STUDY: Population cohort study. SETTING: General population in
      Edinburgh, Scotland. SUBJECTS: A total of 1592 men and women aged 55 to 74 years
      selected at random from age-sex registers of 11 general practices and followed up
      over 12 years. Main outcome measures Changes in ABI for each leg recorded at
      baseline in 1988 and at subsequent 5-year and 12-year clinical examinations.
      RESULTS: Overall, 695 subjects (348 men and 347 women) had valid ABI measurements
      on both legs at all three examinations. At baseline, the ABI was on average.03
      higher in the right leg than the left (P < or =.001). Men had a mean ABI that
      was.07 higher than women (P < or =.001). Mean ABI in the worse leg showed little
      change over 12 years in both men and women. However, in the whole population, the
      ABI in the better leg showed a significant drop, 1.15 to 1.08 (P < or =.001). A
      total of 179 cases of intermittent claudication were identified during the 12
      year follow-up. At baseline, ABI in the worse leg of the claudicants was
      significantly lower than in healthy subjects (.99 vs 1.08; P < or =.01). In
      claudicants, mean ABI in the worse leg fell by.04 over 5 years (P < or =.05) and
      in the better leg showed a highly significant drop of.09 (P < or =.001) to levels
      similar to those of the worse leg. CONCLUSIONS: The mean ABI in the worse leg of
      study subjects showed little progression over 12 years. Individuals with
      intermittent claudication experienced a greater decline in both legs compared
      with those without claudication. Deterioration occurred more rapidly in the limb
      with a higher ABI at baseline, which possibly indicates a systemic tendency to
      atherosclerosis.

PMID- 14681637
TI  - Leg ulceration as a long-term complication of deep vein thrombosis.
AB  - OBJECTIVE: To evaluate the role of deep vein thrombosis as a cause of leg ulcers.
      PATIENTS AND METHODS: A population-based, case-control study was conducted in
      Central and North Auckland, New Zealand. Cases comprised 241 people aged 40 to 99
      years and on the electoral roll, with current leg ulcers (all types). Cases were
      identified by means of notification from health professionals and by self
      referral. Controls were 224 people in the same age group, without leg ulcers, who
      were selected from the electoral roll by using a stratified random sampling
      process. MAIN OUTCOME MEASURES: The occurrence of leg ulceration as a consequence
      of exposure to deep vein thrombosis or being at high risk of deep vein thrombosis
      (that is, people with a family history of deep vein thrombosis, and/or a history
      of leg fracture and/or hip, leg, or foot surgery). RESULTS: After adjustment for
      age, sex, and other potential confounding factors, people who had a diagnosed
      thromboembolism were at almost three times higher risk of having a leg ulcer
      (odds ratio, 2.92; 95% confidence interval (CI), 1.47 to 6.08). In addition,
      people who had been at high risk of a venous thrombosis but were not diagnosed
      with this condition (eg, people with a history of major leg surgery) were also at
      increased risk of ulceration (odds ratio, 2.25; 95% CI, 1.49-3.42). Overall, 56%
      (95% CI, 33% - 71%) of leg ulcers were attributed to being at high risk of deep
      vein thrombosis. CONCLUSIONS: Deep vein thrombosis and factors that place people
      at high risk of deep vein thrombosis are an important cause of leg ulcers in
      older people. This finding strengthens the rationale for the routine and long
      term use of thromboprophylaxis, particularly in high-risk patients.

PMID- 14681638
TI  - Deep axial reflux, an important contributor to skin changes or ulcer in chronic
      venous disease.
AB  - OBJECTIVE: We undertook this cross-sectional study to investigate the
      distribution of venous reflux and effect of axial reflux in superficial and deep
      veins and to determine the clinical value of quantifying peak reverse flow
      velocity and reflux time in limbs with chronic venous disease. PATIENTS AND
      METHODS: Four hundred one legs (127 with skin changes, 274 without skin changes)
      in 272 patients were examined with duplex ultrasound scanning, and peak reverse
      flow velocity and reflux time were measured. Both parameters were graded on a
      scale of 0 to 4. The sum of reverse flow scores was calculated from seven venous
      segments, three in superficial veins (great saphenous vein at saphenofemoral
      junction, great saphenous vein below knee, small saphenous vein) and four in deep
      veins (common femoral vein, femoral vein, deep femoral vein, popliteal vein).
      Axial reflux was defined as reflux in the great saphenous vein above and below
      the knee or in the femoral vein to the popliteal vein below the knee. Reflux
      parameters and presence or absence of axial reflux in superficial or deep veins
      were correlated with prevalence of skin changes or ulcer (CEAP class 4-6).
      RESULTS: The most common anatomic presentation was incompetence in all three
      systems (superficial, deep, perforator; 46%) or in superficial or perforator
      veins (28%). Isolated reflux in one system only was rare (15%; superficial, 28
      legs; deep, 14 legs; perforator, 18 legs). Deep venous incompetence was present
      in 244 legs (61%). If common femoral vein reflux was excluded, prevalence of deep
      venous incompetence was 52%. The cause, according to findings at duplex
      ultrasound scanning, was primary in 302 legs (75%) and secondary in 99 legs
      (25%). Presence of axial deep venous reflux increased significantly with
      prevalence of skin changes or ulcer (C4-C6; odds ratio [OR], 2.7; 95% confidence
      interval [CI], 1.56-4.67). Of 110 extremities with incompetent popliteal vein, 81
      legs had even femoral vein reflux, with significantly more skin changes or ulcer,
      compared with 29 legs with popliteal reflux alone (P =.025). Legs with skin
      changes or ulcer had significantly higher total peak reverse flow velocity (P
      =.006), but the difference for total reflux time did not reach significance (P
      =.084) compared with legs without skin changes. In contrast, presence of axial
      reflux in superficial veins did not increase prevalence of skin changes (OR,
      0.73; 95% CI, 0.44-1.2). Incompetent perforator veins were observed as often in
      patients with no skin changes (C0-C3, 215 of 274, 78%) as in patients with skin
      changes (C4-C6, 106 of 127, 83%; P =.25). CONCLUSION: Continuous axial deep
      venous reflux is a major contributor to increased prevalence of skin changes or
      ulcer in patients with chronic venous disease compared with segmental deep venous
      reflux above or below the knee only. The total peak reverse flow velocity score
      is significantly higher in patients with skin changes or ulcer. It is
      questionable whether peak reverse flow velocity and reflux time can be used to
      quantify venous reflux; however, if they are used, peak reverse flow velocity
      seems to reflect venous malfunction more appropriately.

PMID- 14681639
TI  - Randomized trial and local biological effect of autologous platelets used as
      adjuvant therapy for chronic venous leg ulcers.
AB  - OBJECTIVES: Platelet products have been proposed as adjuvant therapy for wound
      healing. We undertook this study to determine the healing effect of topically
      applied frozen autologous platelets (FAP) on chronic venous ulcers, compared with
      effect of placebo, and whether use of topical FAP modifies local expression of
      vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF),
      interleukin 8 (IL-8), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in
      wound fluid. METHODS: This randomized, placebo-controlled, double-blind trial was
      carried out in institutional practice, with ambulatory patients with proved
      chronic venous leg ulcers. In all patients, whole venous blood was drawn for
      preparation of FAP. FAP or normal saline solution was applied three times per
      week for up to 12 weeks, together with hydrocolloids and standardized compression
      bandages. Leg ulcer surface was assessed with numerical pictures. IL-8, VEGF,
      KGF, and TIMP-1 levels were determined (enzyme-linked immunosorbent assay) in
      wound fluid after each 4 weeks of treatment. RESULTS: Fifteen patients were
      randomized into two groups with comparable leg ulcer characteristics. Mean
      percent reduction in ulcer area was 26.2% in the FAP group versus 15.2% in the
      placebo group (P =.94). One ulcer in each group was completely healed at study
      end. Levels of TIMP-1 increased significantly during FAP treatment. IL-8
      concentration was significantly lower in wound fluid of healing ulcers than in
      the fluid of nonhealing ulcers, in both FAP and placebo groups. Growth factor
      levels were not modified with FAP treatment. CONCLUSION: Topical autologous
      platelets have no significant adjuvant effect on healing of chronic venous leg
      ulcers and increased wound fluid TIMP-1 concentration. Ulcer healing is
      associated with a decrease in wound fluid IL-8.

PMID- 14681640
TI  - Surgical anatomy for subfascial endoscopic perforating vein surgery of laterally
      located perforating veins.
AB  - OBJECTIVES: Endoscopic ligation of perforating veins is useful in treatment of
      perforating vein incompetence. Over the last few years the topic of interest has
      been the medial side of the lower leg; however, laterally located venous ulcers
      (10% of all) are of equal importance. Our poor results with lateral subfascial
      endoscopic perforating vein surgery (SEPS) procedures led us to study the anatomy
      of the perforating veins in the lateral leg. The presence of persistent
      insufficient perforating veins in our patients suggests that our procedure failed
      because of misinterpreted perforator anatomy. METHODS AND RESULTS: Anatomic
      dissection was performed in 16 cadavers in two stages, subcutaneously and
      subfascially. Perforating veins were classified relative to the short saphenous
      vein and intermuscular septa, with coordinates. Three hundred fifty-one
      perforating veins were found, for an average of 21.9 perforating veins per leg.
      The results showed that there is alignment of the perforating veins according to
      the septa between the anterior and peroneal compartment and between the peroneal
      compartment and the superficial dorsal compartment. Most of the perforating veins
      did not correlate with the short saphenous vein. CONCLUSION: Poor clinical
      results of lateral SEPS procedures might be improved after adjustment of the
      procedure for new anatomic information, which shows alignment of perforating
      veins along the intermuscular septa, obligating full septa dissection on the
      lateral side.

PMID- 14681641
TI  - Particle hemodynamics analysis of Miller cuff arterial anastomosis.
AB  - OBJECTIVE: Studies of animal and human below-knee anastomoses with Miller cuffs
      indicate that improved graft patency results from redistribution of intimal
      hyperplasia away from areas critical to flow delivery, such as the arterial toe.
      We hypothesize that particle hemodynamic conditions are a biophysical mechanism
      potentially responsible for the clinically observed shift in intimal hyperplasia
      localization associated with better patency of the Miller configuration. METHODS:
      Computational fluid dynamics analysis of vortical flow patterns, wall shear
      stress fields, and potential for platelet interaction with the vascular surface
      was performed for realistic three-dimensional conventional and Miller cuff distal
      end-to-side anastomoses. Sites of significant platelet-wall interaction,
      including elevated near-wall particle concentrations and stasis, were identified
      with a validated near-wall residence time model, which includes shear stress
      based factors for particle activation and surface reactivity. RESULTS: Particle
      hemodynamics largely coincide with the observed redistribution of intimal
      hyperplasia away from the critical arterial toe region. Detrimental changes in
      wall shear stress vector magnitude and direction are significantly reduced along
      the arterial suture line of the Miller cuff, largely as a result of increased
      anastomotic area available for flow redirection. However, because of strong
      particle-wall interaction, resulting high near-wall residence time contours
      indicate significant intimal hyperplasia along the graft-vein suture line and in
      the vicinity of the arterial heel. CONCLUSIONS: While a number of interacting
      mechanical, biophysical, and technical factors may be responsible for improved
      Miller cuff patency, our results imply that particle hemodynamics conditions
      engendered by Miller cuff geometry provide a mechanism that may account for
      redistribution of intimal hyperplasia. In particular, it appears that a focal
      region of significant particle-wall interaction at the arterial toe is
      substantially reduced with the Miller cuff configuration.

PMID- 14681642
TI  - Functional matrix metalloproteinase-9 polymorphism (C-1562T) associated with
      abdominal aortic aneurysm.
AB  - PURPOSE: Matrix metalloproteinase-9 (MMP-9) is a potent endopeptidase with
      activity against both collagens and elastin. Expression of MMP-9 is elevated in
      vascular disease, and in particular within aneurysm tissues. This study tested
      the hypothesis that the functionally more active T allele of the MMP9 C-1562T
      polymorphism may be overrepresented in patients with abdominal aortic aneurysm
      (AAA) compared with control subjects and patients with atherosclerotic peripheral
      vascular disease (PVD). METHODS: Seven hundred eighty-nine unrelated persons
      (AAA, n = 414; control subjects, n = 203; PVD, n = 172) were genotyped for the
      common C-1562T functional promoter polymorphism of the MMP9 gene. RESULTS:
      Genotypes containing the T allele of this polymorphism were significantly more
      common in patients with AAA compared with both control subjects and patients with
      PVD (adjusted odds ratio, 2.41 and 2.94, respectively). The greatest shift
      between groups was observed in male patients, with a difference of 20.6% in CT/TT
      genotypes. and 12.1% in T allele frequency between patients with AAA compared
      with patients with PVD. CONCLUSIONS: This study provides further evidence to
      support the role of MMP-9 in the pathogenesis of AAA, and indicates that the MMP9
      C-1562T functional polymorphism may represent a genetic component contributing to
      susceptibility to this vascular disease.

PMID- 14681643
TI  - Does large oversizing of self-expandable endoprostheses compensate for aortic
      growth?
AB  - PURPOSE: There is experimental evidence that self-expandable endoprostheses are
      appropriate for compensation of aortic growth. A potential future application
      includes their use in the treatment of aortic coarctation. Yet their behavior is
      poorly investigated. The present study evaluates the performance of largely
      oversized self-expandable endoprostheses (EPs) in the growing porcine aorta and
      the biologic response toward them. METHODS: Twenty oversized EPs (Talent,
      TalentLoPro, Stenway, and Wallstent; nominal lumen area 314 mm(2) [diameter 20
      mm]) were implanted in the descending thoracic aorta of juvenile pigs. Four
      nonoversized EPs (TalentLoPro; nominal lumen area 154 mm(2) [diameter 14 mm])
      served as controls. Cross sections of aorta and EPs were measured by
      intravascular ultrasound (IVUS) at implantation and 3 months follow-up. The
      histologic response was assessed by microscopy. RESULTS: At implantation, the EPs
      were 99 +/- 41% oversized relative to the aortic area [48 +/- 22% in diameter].
      At follow-up, the area of the aortic lumen increased 60 +/- 50%, P <.001 [29 +/-
      23% in diameter]. The Stenway EPs demonstrated the largest prosthetic lumen with
      80 +/- 10% of their nominal area (P =.001). However, the prosthetic lumen area
      was reduced by intimal hyperplasia in all devices. The largest perfused lumen was
      obtained by the TalentLoPro EPs due to their progressive expansion. Nonoversized
      EPs resulted in a significantly smaller perfused lumen (P =.012). The
      inflammatory response to polyester was moderate, whereas polyurethane evoked an
      extensive body-foreign reaction. CONCLUSION: Large oversizing of self-expandable
      EPs is essential in order to maintain a large perfused lumen during aortic
      growth, thereby minimizing the adverse effect of intimal hyperplasia. This was
      best achieved by the TalentLoPro EPs.

PMID- 14681644
TI  - Mechanism of inhibition of matrix metalloproteinase-2 expression by doxycycline
      in human aortic smooth muscle cells.
AB  - Degradation of the extracellular matrix components elastin and collagen has been
      implicated in vascular diseases, including abdominal aortic aneurysm (AAA) and
      atherosclerotic plaque rupture. Increased expression of matrix metalloproteinases
      (MMPs) is involved in these disease processes. Our previous studies have
      demonstrated that MMP-2 derived from mesenchymal cells is required for aneurysm
      development in a murine model. Doxycycline is a nonspecific inhibitor of MMPs. In
      the present study, the mechanisms of the inhibitory effects of doxycycline on MMP
      2 expression from cultured human aortic smooth muscle cells (SMCs) and human
      aortic aneurysm tissue explants were studied. Doxycycline inhibited MMP-2
      expression from cultured SMCs in a concentration-dependent manner (5-40
      microg/mL; inhibitory concentration of 50%, 6.5 microg/mL). At normal therapeutic
      serum concentration (5 microg/mL) doxycycline significantly reduced MMP-2
      production from SMCs (37%; P <.05), which were stimulated with conditioned media
      from macrophage or lymphocyte co-culture simulating the inflammatory milieu of
      AAA tissue. This correlated with a decrease in MMP-2 mRNA half-life, from 49
      hours to 28 hours, which suggests that doxycycline inhibits SMC MMP-2 production
      in part by reducing MMP-2 mRNA stability. When AAA tissue was cultured for 10
      days with doxycycline at concentrations of 2.5 to 40 microg/mL, the media
      exhibited a concentration-dependent decrease in both active and latent forms of
      MMP-2 and MMP-9. Doxycycline at a concentration of 5 microg/mL reduced active and
      latent MMP-2 secreted from cultured AAA tissue by 50% and 30%, respectively (P
      <.05). These study findings demonstrate that doxycycline at standard therapeutic
      serum concentrations inhibits MMP-2 expression from cultured human aortic SMCs
      and AAA tissue explants. Inasmuch as MMP activity contributes to extracellular
      matrix degradation in AAAs and atherosclerotic plaque, doxycycline may have
      potential value in treating these diseases.

PMID- 14681645
TI  - Multiple bacteria in aortic aneurysms.
AB  - OBJECTIVE: The purpose of the present study was to reexamine the possibility that
      bacteria, particularly anaerobes, are present in aortic aneurysms. METHODS: From
      December 2000 to November 2001, 53 samples from aneurysm walls were collected
      from 49 patients during reconstructive surgery. The tissue specimens were
      sectioned and cultured under anaerobic conditions. Twenty-eight specimens were
      also subjected to scanning or transmission electron microscopy. RESULTS:
      Anaerobic cultivation yielded bacteria in 14 of the 53 samples (26.4%). All
      bacteria were gram-positive cocci or rods from nine genera and 12 species. Five
      cultures (35%) were mixed, containing two bacterial species. Mixed aerobic and
      anaerobic species were found in four samples (28.5%). Anaerobic bacteria were
      recovered from 10 of 14 positive cultures (71%). Among anaerobes found were
      Propionibacterium acnes, Propionibacterium granulosum, Actinomyces viscosus,
      Actinomyces naeslundii, and Eggerthella lenta. Coaggregating bacteria of
      different sizes and structure were found on the aneurysm walls and inside the
      intravascular plaque at electron microscopy. Bacteria were found in 20 of the 28
      samples (71%) examined with scanning or transmission electron microscopy.
      CONCLUSION: Multiple bacteria, many of which did not belong to the indigenous
      skin microflora, colonize aortic aneurysms. It is not clear whether the bacteria
      contribute to weakening of the aortic wall by eliciting inflammation or whether
      they are secondary colonizers of aneurysms.

PMID- 14681646
TI  - In vivo noninvasive identification of cell composition of intimal lesions: a
      combined approach with ultrasonography and immunocytochemistry.
AB  - PURPOSE: We investigated whether differences in cellular composition of the
      shoulder region of carotid plaque, a cell-rich, debris-free area, can be revealed
      with computer-driven analysis of ultrasound scans. METHODS: In 26 patients
      referred for carotid endarterectomy, the shoulder region of plaque eligible for
      surgical removal was identified with ultrasound scanning. Digital images were
      obtained and evaluated with a specially developed computer-driven system (Medical
      Image Processing [MIP]). The gray level distribution of the region of interest
      (ROI), along with some statistical parameters exploring the spatial distribution
      of pixels, such as entropy and second angular moment, were analyzed. In the
      specimen retrieved at surgery, the area corresponding to the ROI was selected.
      Cryosections were tested at immunocytochemistry with monoclonal antibodies
      specific to smooth muscle cells (SMCs), macrophages), and lymphocytes.
      Computerized image analysis was performed to quantify each cellular component of
      the lesion. RESULTS: Mean gray levels were related positively to the content of
      SMCs (r = 0.576, P =.002) and negatively to the content of macrophages (r = 
      0.555, P =.003). Lymphocytes did not show any correlation. Prevalence of SMCs,
      expressed as the ratio SMC/(SMC + macrophages), was related positively with
      entropy (r = 0.517, P =.007) and negatively with the second angular moment (r = 
      0.422, P =.032). The quartiles of gray level were useful for detecting
      significant differences in terms of cellular composition. CONCLUSIONS: Some
      cellular features of the shoulder region of plaque are associated with specific
      videodensitometric patterns evaluated with MIP. This approach enables in vivo
      noninvasive prediction and monitoring of cell composition of the shoulder region,
      and could be extended to study of the thickened intima.

PMID- 14681647
TI  - L-arginine improves endothelial vasoreactivity and reduces thrombogenicity after
      thrombolysis in experimental deep venous thrombosis.
AB  - PURPOSE: Nitric oxide (NO) is important in regulation of platelet aggregation,
      endothelial function, and intravascular thrombosis. The purposes of this study
      were to assess the effect of thrombolysis on endothelial function in a porcine
      model of deep venous thrombosis (DVT) and to evaluate the effect of NO precursor
      l-arginine on endothelial function after thrombolytic therapy. METHODS: DVT was
      created in bilateral iliac veins by deploying a self-expanding stent-graft that
      incorporated an intraluminal stenosis, from a groin approach. Five pigs underwent
      sham operation. After 7 days of DVT, animals were randomized to three groups:
      saline pulse-spray (saline group, n = 5), thrombolytic pulse-spray with tissue
      plasminogen activator (alteplase, 8 mg; t-PA group, n = 5), and thrombolytic
      pulse-spray plus intravenous l-arginine (20 mmol/L; arginine group, n = 5). At 2
      weeks iliac vein patency was evaluated at venography and intravascular ultrasound
      scanning. NO level was determined with a chemiluminescent assay of the nitrite
      and nitrate metabolites (NO(x)). Thrombogenicity was evaluated with radiolabeled
      platelet and fibrin deposition. Veins were harvested and evaluated with light
      microscopy and scanning electron microscopy. Endothelial function was evaluated
      with organ chamber analysis. RESULTS: All iliac veins remained patent at 2 weeks.
      The luminal areas in the sham, saline, t-PA, and arginine groups were 53 +/- 23
      mm(2), 14 +/- 11 mm(2), 34 +/- 19 mm(2), and 42 +/- 21 mm(2), respectively. No
      difference in endothelial cell structure was observed between the three treatment
      groups at light microscopy or scanning electron microscopy. Although no
      difference in fibrin deposition was noted among the three treatment groups,
      decreased platelet deposition occurred in the arginine group compared with the
      saline or t-PA groups (P <.05). The arginine group showed greater endothelial
      dependent relaxation compared with the t-PA or saline groups (73% +/- 23% vs 49%
      +/- 18% and 32% +/- 21%; P <.05). Local NO(x) level in the arginine group was
      correspondingly higher compared with the saline or t-PA groups (1.8 +/- 0.3
      micromol/L vs 0.3 +/- 0.05 micromol/L and 0.2 +/- 0.04 micromol/L; P <.05).
      CONCLUSIONS: NO precursor l-arginine supplementation enhances NO production at
      sites of venous thrombosis. Moreover, l-arginine preserves endothelial
      vasoreactivity and reduces platelet deposition after thrombolysis in iliac DVT.
      These data suggest that l-arginine may preserve endothelial function after
      thrombolysis and may reduce the likelihood of postthrombotic syndrome.

PMID- 14681648
TI  - Use of fascia-peritoneum patch as a pledget for an infected aortic stump.
AB  - Treatment of aortic prosthetic graft infections remains a challenge. One
      frequently encountered technical difficulty when removing an infected prosthetic
      aortic graft is how to close a short, friable remnant aortic stump. We present
      three case reports in which we used a layer of posterior rectus fascia-peritoneum
      to bolster oversewing a short infected aortic stump after removal of an infected
      aortic graft. All three patients underwent staged extra-anatomic axillary-to
      femoral artery bypass procedures, with subsequent removal of the infected aortic
      graft as a second operation. Two of the three procedures were semi-elective, and
      one was done urgently because of a recurrent aortoenteric fistula. All three
      patients had less than 1 cm of remaining aortic neck below the renal arteries for
      closure. In each instance a segment of autogenous posterior rectus fascia
      peritoneum was harvested and used as a circumferential pledget to bolster the
      anastomosis. No patient had stump blowout, and in no case was there computed
      tomography evidence of aneurysmal enlargement of the stump with follow-up of 12
      and 24 months in two of the three survivors. Use of autogenous fascia-peritoneum
      is a durable and effective method to assist stump closure and prevent stump
      blowout after removal of infected aortic grafts.

PMID- 14681649
TI  - Endovascular repair of a penetrating thoracic aortic ulcer by way of the carotid
      artery.
AB  - INTRODUCTION: Endovascular repair of thoracic aortic lesions offers an attractive
      alternative to traditional open repair. Access to the thoracic aorta can
      occasionally be challenging because of large device size and vessel tortuosity.
      Traditional access by way of the femoroiliac vessels might not be possible in the
      setting of synchronous iliac occlusive disease. MATERIALS AND METHODS: A 63-year
      old woman presented with a 7.1-cm symptomatic, penetrating ulcer of the
      descending thoracic aorta. The patient's severe pulmonary disease prohibited an
      open repair. A Talent endoprosthesis was placed under compassionate use with
      approval of the institutional review board. The graft was placed by way of the
      left common carotid artery because of severe iliac occlusive disease. RESULTS:
      The thoracic endograft was successfully placed with exclusion of the
      pseudoaneurysm. The patient's chest pain resolved immediately. She developed mild
      left-sided weakness from a postoperative right anterior cerebral artery stroke
      that quickly resolved. The patient was discharged on postoperative day 5. No
      aortic endoleak was noted on follow-up computerized tomography scan at 1 month.
      CONCLUSIONS: Endovascular repair should be considered in patients with thoracic
      aortic aneurysms, particularly those with severe medical comorbidities. Placement
      by way of the common carotid artery is technically feasible in the setting of
      synchronous aortoiliac disease.

PMID- 14681650
TI  - Treatment of portal venous thrombosis with selective superior mesenteric artery
      infusion of recombinant tissue plasminogen activator.
AB  - Portal and mesenteric venous thrombosis is an uncommon condition that is usually
      treated with systemic anticoagulation. Catheter-directed thrombolysis via the
      superior mesenteric artery may be a viable adjunct to treatment of this
      potentially morbid condition. We present a case of portal and mesenteric venous
      thrombosis treated with systemic anticoagulation and catheter-directed infusion
      of tissue plasminogen activator via the superior mesenteric artery.

PMID- 14681651
TI  - Caval and ureteral obstruction secondary to an inflammatory abdominal aortic
      aneurysm.
AB  - Inflammatory abdominal aortic aneurysms (IAAA) represent 3% to 10% of all
      abdominal aortic aneurysms. Obstructive uropathy is a well-described feature of
      IAAAs, but venous complications are unusual secondary to IAAA. The authors report
      a patient presenting with acute renal failure and deep venous thrombosis
      secondary to an IAAA. We believe this represents the first case of an IAAA
      manifesting as combined inferior vena cava compression and associated obstructive
      uropathy. Successful operative repair was performed. With resolution of the
      retroperitoneal inflammation, long-term follow-up revealed spontaneous release of
      both ureteral and caval compression.

PMID- 14681652
TI  - Combined open and endovascular repair of a syphilitic aortic aneurysm.
AB  - The use of endovascular stent grafts in the repair of thoracic aortic aneurysms
      has provided an alternative means of treatment, particularly in the high-risk
      patient who may not tolerate conventional open repair. The combination of
      conventional surgery and endovascular repair may allow for successful treatment
      in patients with anatomy unsuitable for repair entirely by endovascular means
      alone. We present the case of a patient with a syphilitic thoracic aortic
      aneurysm involving the aortic arch and descending thoracic aorta. He underwent a
      staged repair with an elephant trunk reconstruction of the aortic arch followed
      by endovascular repair of the descending thoracic aorta. This is the first
      reported case of the repair of a syphilitic aneurysm by means of endovascular
      techniques.

PMID- 14681653
TI  - Endovascular abdominal aortic aneurysm repair to prevent rupture in a patient
      requiring lithotripsy.
AB  - Extracorporeal shock wave lithotripsy (ESWL) for urolithiasis may result in
      rupture of a coexistent abdominal aortic aneurysm (AAA). We report a patient who
      required ESWL and who had an AAA. Open surgery was precluded by morbid obesity
      and persisting incisional hernias after mesh repair. Endovascular AAA repair
      (EVAR) with bifurcated grafts was precluded by an 11-mm distal aorta. EVAR with
      stacked tubular AneuRx components was performed, followed by ESWL. The AAA was
      excluded, and the integrity and position of the endografts were not altered by
      ESWL.

PMID- 14681654
TI  - Primary malignant tumors of the aorta: clinical presentation, treatment, and
      course of different entities.
AB  - OBJECTIVE: The objective of this study was to analyze possible correlations
      between the clinical presentation and the course of patients with different types
      of primary malignant aortic tumors. METHODS: A single academic center's
      experience was reviewed retrospectively. RESULTS: Four patients with primary
      malignant tumors of the aorta were treated in an 11-year period. Three different
      histologic entities were found: malignant fibrous histiocytoma, epitheloid
      angiosarcoma, and unclassified sarcoma. Two female patients presenting with
      clinical symptoms of vasculitis proved to have epitheloid aortic sarcoma. Both
      developed diffuse metastasis to bone and skin with initial lymphatic disease in
      the groin. The other patients developed local recurrence and pulmonary
      metastasis. Survival of the 4 patients was 11, 20, and 51 months, 1 patient with
      metastatic disease is still alive 6 months after surgery. CONCLUSION: Different
      types of malignant aortic tumors seem to have different clinical presentation and
      course.

PMID- 14681655
TI  - Inferior mesenteric artery aneurysm in Behcet syndrome.
AB  - We present a case report of an aneurysm of the inferior mesenteric artery,
      associated with occlusion of the celiac, superior mesenteric, and left renal
      arteries and severe stenosis in the right renal artery, in a 48-year-old patient
      with Behcet syndrome. The meandering inferior mesenteric artery, with an aneurysm
      28 mm in greatest dimension, was the blood supply source for the intraperitoneal
      viscera. Aneurysm resection and reimplantation of the inferior mesenteric artery,
      and right renal artery bypass grafting with saphenous vein was performed. To our
      knowledge, this is the first reported case of inferior mesenteric artery aneurysm
      caused by Behcet syndrome.

PMID- 14681656
TI  - Inferior vena cava endograft to control surgically inaccessible hemorrhage.
AB  - Open surgical repair of retrohepatic inferior vena cava (IVC) injuries can be
      technically difficult, usually requiring extensive hepatic mobilization and
      associated with significant morbidity. We report a case of uncontrolled
      hemorrhage from the retrohepatic inferior vena cava (IVC), which occurred during
      attempted resection of a large retroperitoneal leiomyosarcoma, and was
      successfully managed using an endoluminal stent-graft. This case demonstrates
      that endoluminal grafts can be successfully applied to control life-threatening
      hemorrhage arising from lesions in the retrohepatic IVC that are otherwise
      extremely difficult or inaccessible to direct surgical repair.

PMID- 14681657
TI  - Multiple arterial aneurysms.

PMID- 14681659
TI  - Limits of confidentiality: Disclosure of HIV seropositivity.

PMID- 14681660
TI  - Regarding response to "Vein transposition in the forearm for autogenous
      hemodialysis access" and "Basilic vein transposition: an underused autologous
      alternative to prosthetic dialysis angioaccess".

PMID- 14681679
TI  - Photodamage to multiple Bcl-xL isoforms by photodynamic therapy with the
      phthalocyanine photosensitizer Pc 4.
AB  - The antiapoptotic oncoprotein Bcl-2 is now a recognized phototarget of
      photodynamic therapy (PDT) with the phthalocyanine Pc 4 and with other
      mitochondrion-targeting photosensitizers. Photodamage, observed on Western blots
      as the loss of the native 26-kDa Bcl-2 protein, is PDT dose dependent and occurs
      in multiple cell lines, in the cold, and immediately upon photoirradiation. In
      our initial study, no photochemical damage was observed to Bcl-xL, in spite of
      its similarity in size, sequence, location and function to Bcl-2. The original
      study used a commercial anti-Bcl-xS/L antibody. We have revisited this issue by
      examining Western blots developed using one of three epitope-specific anti-Bcl-xL
      antibodies from commercial sources, a polyclonal antibody generated to the entire
      protein, as well as the antibody used previously. All five Bcl-xL antibodies
      recognized bacterially expressed Bcl-xL, but not Bcl-2, whereas an anti-Bcl-2
      antibody recognized Bcl-2 and not Bcl-xL. All five Bcl-xL antibodies recognized
      at least one protein migrating at approximately 30 kDa; two of the antibodies
      recognized an additional band, migrating at approximately 33 or approximately 24
      kDa. We now observe Pc 4-PDT-induced photodamage to all Bcl-xL-related proteins,
      except the 33-kDa species, in several human cancer cell lines. The results
      indicate that, in addition to the expected quantitative differences that may
      reflect exposure of individual epitopes, the antibodies also detect proteins of
      different apparent molecular weights that may be distinct isoforms or post
      translationally modified forms of Bcl-xL. No evidence for PDT-induced
      phosphorylation or degradation was observed. Bcl-xL localized to mitochondria was
      considerably more sensitive to photodamage than was Bcl-xL in the cytosol,
      indicating that as previously found for Bcl-2, Bcl-xL must be membrane localized
      to be photosensitive.

PMID- 14681681
TI  - Activating BRAF and N-Ras mutations in sporadic primary melanomas: an inverse
      association with allelic loss on chromosome 9.
AB  - We searched and report mutations in the BRAF and N-ras genes in 22 out of 35 (63
      percent) primary sporadic melanomas. In three melanomas, mutations were
      concomitantly present in both genes. In all, 10 out of 12 mutations in the BRAF
      gene involved the 'hot spot' codon 600 (In all communications on mutations in the
      BRAF gene, the nucleotide and codon numbers have been based on the NCBI gene bank
      nucleotide sequence NM_004333. However, according to NCBI gene bank sequence with
      accession number NT_007914, there is a discrepancy of one codon (three
      nucleotides) in exon 1 in the sequence with accession number NM_004333. The
      sequence analysis of exon 1 of the BRAF gene in our laboratory has shown that the
      sequence derived from NT_007914 is correct (Kumar et al., 2003). Due to the
      correctness of the latter, sequence numbering of codons and nucleotides after
      exon 1 are changed by +1 and +3, respectively.), one tandem CT1789-90TC base
      change represented a novel mutation and another mutation caused a G466R amino
      acid change within the glycine-rich loop in the kinase domain. Mutations in the N
      ras gene in 11 melanomas were at codon 61 whereas two melanomas carried mutations
      in codon 12 including a tandem mutation GG>AA. We observed an inverse association
      between BRAF/N-ras mutations and the frequency of loss of heterozygosity (LOH) on
      chromosome 9 at 10 different loci. Melanomas with BRAF/N-ras mutations showed a
      statistically significant decreased frequency of LOH on chromosome 9 compared
      with cases without mutations (mean fractional allelic loss (FAL)=0.29+/-0.23 vs
      0.72+/-0.33; t-test, P=0.0001). Difference in the FAL value between tumours with
      and without BRAF/N-ras mutations on 33 loci on five other chromosomes was not
      statistically significant (mean FAL 0.17+/-0.19 vs 0.25+/-0.22; t-test, P=0.24).
      Melanoma cases with BRAF/N-ras mutations were also associated with lower age at
      diagnosis than cases without mutations (mean age 80.38+/-7.24 vs 65.77+/-19.79
      years; t-test, P=0.02). Our data suggest that the occurrence of BRAF/N-ras
      mutations compensate the requirement for the allelic loss at chromosome 9, which
      is one of the key events in melanoma.

PMID- 14681680
TI  - The MEK-1/ERKs signalling pathway is differentially involved in the self-renewal
      of early and late avian erythroid progenitor cells.
AB  - Making decisions between self-renewal and differentiation is a central ability of
      stem cells. Elucidation of molecular networks governing this decision is
      therefore of prime importance. A model of choice to explore this question is
      represented by chicken erythroid progenitors, in which self-renewal versus
      differentiation as well as progenitor maturation are regulated by external factor
      combinations. We used this system to study whether similar or different
      signalling pathways were involved in the self-renewal of early, immature or more
      mature erythroid progenitors. We show that a transforming growth factor (TGF)
      alpha-activated Ras/MEK-1/ERK1/2 pathway is strictly required for immature self
      renewing cells but becomes fully dispensable when those cells are induced to
      differentiate. Consequently, pharmacological inhibition of this pathway led to
      spontaneous differentiation, only dependent on the presence of survival signals.
      Conversely, ectopic expression of a constitutive form of MEK-1 stimulates renewal
      and arrests differentiation process. Finally, we demonstrate that the ERK/MAPK
      signalling pathway is required in early but not in late primary erythroid
      progenitors, which can be turned into each other by different growth factor
      combinations specifically driving their renewal. To the best of our knowledge,
      this is the first description of a central role of ERK/MAPK signalling in
      regulating progenitor plasticity in the same cell type under different
      environmental conditions.

PMID- 14681682
TI  - hScrib is a functional homologue of the Drosophila tumour suppressor Scribble.
AB  - Scribble (scrib), discs large (dlg) and lethal giant larvae (lgl) encode proteins
      that regulate cell polarity and have been identified as neoplastic tumour
      suppressor genes in Drosophila melanogaster. Here, we have used the Drosophila
      model system to provide the first functional evidence that human Scribble
      (hScrib) can act as a tumour suppressor. We show that hScrib protein displays
      highly polarized localization in mammalian epithelial cells and colocalizes with
      mammalian Dlg, similar to D. melanogaster Scribble (DmScrib) distribution in
      Drosophila epithelium. Furthermore, hScrib can rescue the polarity and tumorous
      overgrowth defects of scrib mutant Drosophila. hScrib therefore can act as an
      effective tumour suppressor in vivo, regulating both apical-basal polarity and
      cellular proliferation in a manner similar to that of DmScrib in Drosophila.
      These data demonstrate that hScrib is a functional homologue of DmScrib and
      therefore predict an important role for hScrib in the suppression of mammalian
      tumorigenesis.

PMID- 14681683
TI  - Mammary gland development requires syndecan-1 to create a beta-catenin/TCF
      responsive mammary epithelial subpopulation.
AB  - Mice with a null mutation in the cell surface heparan sulfate (HS) proteoglycan,
      syndecan-1 (Sdc1), develop almost normally, but resist mammary tumor development
      in response to Wnt-1. Here, we test the hypothesis that Sdc1 promotes Wnt-1
      induced tumor development by interacting with the Wnt cell surface signaling
      complex. Thus, the response of Sdc1-/- mammary epithelial cells (mecs) to the
      intracellular, activated Wnt signal transducer, DeltaNbeta-catenin, was assayed
      both in vitro and in vivo, to test whether beta-catenin/TCF transactivation was
      Sdc1-independent. Surprisingly, we found that the expression of a canonical Wnt
      pathway reporter, TOP-FLASH, was reduced by 50% in both unstimulated Sdc1-/- mecs
      and in stimulated cells responding to Wnt1 or DeltaNbeta-catenin. Tumor
      development in response to DeltaNbeta-catenin was also significantly delayed on a
      Sdc1-/- background. Furthermore, the average beta-catenin/TCF transactivation per
      cell was normal in Sdc1-/- mec cultures, but the number of responsive cells was
      reduced by 50%. Sdc1-/- mecs show compensatory changes that maintain the number
      of HS chains, hence these experiments cannot test the coreceptor activity of HS
      for Wnt signaling. We propose that TCF-dependent transactivational activity is
      suppressed in 50% of cells in Sdc1-/- glands, and conclude that the major effect
      of Sdc1 does not map to the activity of the Wnt signaling complex, but to another
      pathway to create or stabilize the beta-catenin/TCF-responsive tumor precursor
      cells in mouse mammary gland.

PMID- 14681684
TI  - Suppression of UVB-induced phosphorylation of mitogen-activated protein kinases
      and nuclear factor kappa B by green tea polyphenol in SKH-1 hairless mice.
AB  - Studies from our laboratory have shown that epigallocatechin-3-gallate, the major
      polyphenol present in green tea, inhibits ultraviolet (UV)B-exposure-mediated
      phosphorylation of mitogen-activated protein kinases (MAPKs) (Toxicol. Appl.
      Pharmacol. 176: 110-117, 2001) and activation of nuclear factor kappa B (NF
      kappaB) (Oncogene 22: 1035-1044, 2003) pathways in normal human epidermal
      keratinocytes. This study was designed to investigate the relevance of these
      findings to the in vivo situations in SKH-1 hairless mouse model, which is
      regarded to have relevance to human situations. SKH-1 hairless mice were
      topically treated with GTP (5 mg/0.2 ml acetone/mouse) and were exposed to UVB 30
      min later (180 mJ/cm2). These treatments were repeated every alternate day for 2
      weeks, for a total of seven treatments. The animals were killed 24 h after the
      last UVB exposure. Topical application of GTP resulted in significant decrease in
      UVB-induced bifold-skin thickness, skin edema and infiltration of leukocytes.
      Employing Western blot analysis and immunohistochemical studies, we found that
      GTP resulted in inhibition of UVB-induced: (i) phosphorylation of extracellular
      signal-regulated kinases (ERK1/2), (ii) c-Jun N-terminal kinases, and (iii) p38
      protein expression. Since NF-kappaB plays a major role in inflammation and cell
      proliferation, we assessed the effect of GTP on UVB-mediated modulations in the
      NF-kappaB pathway. Our data demonstrated that GTP inhibited UVB-induced: (i)
      activation of NF-kappaB, (ii) activation of IKKalpha, and (iii) phosphorylation
      and degradation of IkappaBalpha. Our data suggest that GTP protects against the
      adverse effects of UV radiation via modulations in MAPK and NF-kappaB signaling
      pathways, and provides molecular basis for the photochemopreventive effect of GTP
      in an in vivo animal model system.

PMID- 14681685
TI  - Hypermethylation of the Ink4b locus in murine myeloid leukemia and increased
      susceptibility to leukemia in p15(Ink4b)-deficient mice.
AB  - The Ink4b gene (Cdkn2b) encodes p15(Ink4b), a cyclin-dependent kinase inhibitor.
      It has been implicated in playing a role in the development of acute myeloid
      leukemia (AML) in man, since it is hypermethylated with high frequency. We
      provide evidence that the gene is a tumor suppressor for myeloid leukemia in
      mice. The evidence is twofold: (1) retrovirus-induced myeloid leukemias of the
      myelomonocytic phenotype were found to have hypermethylation of the 5' CpG island
      of the Ink4b gene, and this could be correlated with reduced mRNA expression, as
      demonstrated by TaqMan real-time PCR. p15(Ink4b) mRNA expression in a leukemia
      cell line, with hypermethylation at the locus, was induced following treatment
      with 5-aza-2'-deoxycytidine. (2) Targeted deletion of one allele in mice by
      removal of exon 2 increases their susceptibility to retrovirus-induced myeloid
      leukemia. Mice deficient in both alleles were not more susceptible to myeloid
      disease than those deficient in one allele, raising the possibility that there
      are opposing forces related to the development of myeloid leukemia in Ink4b null
      mice.

PMID- 14681686
TI  - Nrf2 regulates the sensitivity of death receptor signals by affecting
      intracellular glutathione levels.
AB  - Nrf2 is a basic leucine zipper transcriptional activator that is essential for
      the coordinate transcriptional induction of various antioxidant drug-metabolizing
      enzymes. Numerous studies have firmly established Nrf2's importance in protection
      from oxidative stress and certain chemical insults. Given the protective function
      of Nrf2, surprisingly few studies have focused on the relationship between Nrf2
      and apoptosis. Therefore, we analysed how Nrf2 influences Fas signaling using
      Nrf2-deficient T cells. At a concentration of 1 microg/ml, the anti-Fas antibody
      induced 60% of cell death in Nrf2-deficient cultured thymocytes while, using the
      same treatment, only 40% of Nrf2 wild-type thymocytes died (P<0.05). Nrf2
      deficiency enhances the sensitivity of Fas-mediated apoptosis in T cells. Next we
      examined the effect of Nrf2 deficiency during hepatocellular apoptosis in vivo.
      In comparison to wild-type mice, Nrf2-deficient mice displayed more severe
      hepatitis after induction with the anti-Fas antibody or tumor necrosis factor
      (TNF)-alpha. The enhanced sensitivity to anti-Fas or TNF-alpha stimulation was
      restored by preadministration of glutathione ethyl monoester, a compound capable
      of passing the cell membrane and upregulating the intracellular levels of
      glutathione. The results indicated that Nrf2 activity regulates the sensitivity
      of death signals by means of intracellular glutathione levels.

PMID- 14681687
TI  - Rapamycin induces the fusion-type independent downregulation of the EWS/FLI-1
      proteins and inhibits Ewing's sarcoma cell proliferation.
AB  - Ewing's sarcoma (ES) is the prototype of a family of tumors (ESFT) of
      neuroectodermal origin formed by small, round cells with limited neural
      differentiation, which arise most frequently within bones in children or
      adolescents. The proliferation of ESFT cells is highly dependent on the
      establishment of, and signaling through several growth factor-mediated autocrine
      loops. The mammalian target of rapamycin (mTOR) is a central regulator of
      translation and cell proliferation, involved in the cellular response to various
      nutritional, stress and mitogenic effectors. As mTOR has recently been associated
      with certain human cancers, we investigated the possibility that mTOR played a
      role in the regulation of ES cell proliferation. Results showed that ES cell
      lines carrying EWS/FLI-1 alleles of different types expressed different levels of
      total and phosphorylated mTOR protein. We demonstrate that rapamycin, an mTOR
      inhibitor, efficiently blocked the proliferation of all cell lines by promoting
      cell cycle arrest at the G1 phase. This was paralleled by the downregulation of
      the levels of the EWS/FLI-1 proteins, regardless of their fusion type, and the
      concomitant restoration of the expression of the TGF-beta type 2 receptor
      (TGFbeta RII), which is known to be repressed by several EWS-ETS fusion proteins.
      The expression of a rapamycin-resistant mTOR construct prevented both the
      proliferation blockade and the EWS/FLI-1 downregulation. These data demonstrate
      that mTOR signaling plays a central role in ES cell pathobiology and strongly
      suggest that the use of rapamycin as a cytostatic agent may be an efficient tool
      for the treatment of ES patients.

PMID- 14681688
TI  - Prevention of non-melanoma skin cancer by targeting ultraviolet-B-light
      signalling.

PMID- 14681689
TI  - Mucins in cancer: protection and control of the cell surface.

PMID- 14681690
TI  - Two mitotic kinesins cooperate to drive sister chromatid separation during
      anaphase.
AB  - During anaphase identical sister chromatids separate and move towards opposite
      poles of the mitotic spindle. In the spindle, kinetochore microtubules have their
      plus ends embedded in the kinetochore and their minus ends at the spindle pole.
      Two models have been proposed to account for the movement of chromatids during
      anaphase. In the 'Pac-Man' model, kinetochores induce the depolymerization of
      kinetochore microtubules at their plus ends, which allows chromatids to move
      towards the pole by 'chewing up' microtubule tracks. In the 'poleward flux'
      model, kinetochores anchor kinetochore microtubules and chromatids are pulled
      towards the poles through the depolymerization of kinetochore microtubules at the
      minus ends. Here, we show that two functionally distinct microtubule
      destabilizing KinI kinesin enzymes (so named because they possess a kinesin-like
      ATPase domain positioned internally within the polypeptide) are responsible for
      normal chromatid-to-pole motion in Drosophila. One of them, KLP59C, is required
      to depolymerize kinetochore microtubules at their kinetochore-associated plus
      ends, thereby contributing to chromatid motility through a Pac-Man-based
      mechanism. The other, KLP10A, is required to depolymerize microtubules at their
      pole-associated minus ends, thereby moving chromatids by means of poleward flux.

PMID- 14681691
TI  - Immunological needles in the gene therapy haystack: applying a genetic paradigm
      to gene therapy.

PMID- 14681692
TI  - Identification of multiple genetic loci that regulate adenovirus gene therapy.
AB  - A key aspect of the immune response to adenovirus (Ad) gene therapy is the
      generation of a cytotoxic T-cell (CTL) response. To better understand the genetic
      network underlying these events, 20 strains of C57BL/6 x DBA/2 (BXD) recombinant
      inbred (RI) mice were administered with AdLacZ and analyzed at days 7, 21, 30,
      and 50 for liver beta-galactosidase (LacZ) expression and CTL response. Sera
      levels of interferon gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha),
      and interleukin-6 (IL-6) were analyzed at different times after AdLacZ. There was
      a distinct strain-dependent expression of LacZ, which was strongly correlated
      with the CTL response. Among the five BXD RI strains that exhibited significantly
      prolonged LacZ expression, four also exhibited a marked defect in the production
      of Ad-specific CTL. There was a strong correlation between the sera levels of IFN
      gamma, TNF-alpha, and IL-6, but cytokine responses were not significantly
      correlated with LacZ expression or the CTL response. Quantitative trait loci
      regulating LacZ on day 30 were found on chromosome (Chr) 19 (33 cM) and Chr 15
      (42.8 cM). Cytotoxicity mapped to Chr 7 (41.0 and 57.4-65.2 cM), Chr 15 (61.7
      cM), and Chr X (27.8 cM). IFN-gamma production mapped to Chr 18 (22, 27, and 32
      cM) and Chr 11 (64.0 cM). TNF-alpha and IL-6 production mapped to Chr 6 (91.5 cM)
      Chr 9 (42.0 cM) and Chr 8 (52 and 73.0 cM). These results indicate that different
      strains of mice exhibit different pathways for effective clearance of AdLacZ
      depending on genetic polymorphisms and interactions at multiple genetic loci.

PMID- 14681693
TI  - Localized gene delivery using antibody tethered adenovirus from polyurethane
      heart valve cusps and intra-aortic implants.
AB  - The present study investigated a novel approach for gene therapy of heart valve
      disease and vascular disorders. We formulated and characterized implantable
      polyurethane films that could also function as gene delivery systems through the
      surface attachment of replication defective adenoviruses using an anti-adenovirus
      antibody tethering mechanism. Our hypothesis was that we could achieve site
      specific gene delivery to cells interacting with these polyurethane implants, and
      thereby demonstrate the potential for intravascular devices that could also
      function as gene delivery platforms for therapeutic vectors. Previous research by
      our group has demonstrated that polyurethane elastomers can be derivatized post
      polymerization through a series of chemical reactions activating the hard segment
      amide groups with alkyl bromine residues, which can enable a wide variety of
      subsequent chemical modifications. Furthermore, prior research by our group
      investigating gene delivery intravascular stents has shown that collagen-coated
      balloon expandable stents can be configured with anti-adenovirus antibodies via
      thiol-based chemistry, and can then tether adenoviral vectors at doses that lead
      to high levels of localized arterial neointima expression, but with virtually no
      distal spread of vector. Thus, we sought to create two-device configurations for
      our investigations building on this previous research. (1) Polyurethane films
      coated with Type I collagen were thiol activated to permit covalent attachment of
      anti-adenovirus antibodies to enable gene delivery via vector tethering. (2) We
      also formulated polyurethane films with direct covalent attachment of anti
      adenovirus antibodies to polyurethane hard segments derivatized with alkyl-thiol
      groups, thereby also enabling tethering of replication-defective adenoviruses.
      Both formulations demonstrated highly localized and efficient transduction in
      cell culture studies with rat arterial smooth muscle cells. In vivo experiments
      with collagen-coated polyurethane films investigated an abdominal aorta implant
      model in pigs using a button configuration that simulated the blood contacting
      environment of a vascular graft. One week explants of the collagen-coated
      polyurethane films demonstrated 14.3+/-2.5% of neointimal cells on the surface of
      the implant transduced with green fluorescent protein - adenovirus (AdGFP) vector
      loadings of 1 x 10(8) PFU. PCR studies demonstrated no detectable vector DNA in
      blood or distal organs. Similarly, polyurethane films with direct attachment of
      antivector antibodies to the surface were used in sheep pulmonary valve leaflet
      replacement studies, simulating the blood contacting environment of a prosthetic
      heart valve cusp. Polyurethane films with antibody tethered AdGFP vector (10(8)
      PFU) demonstrated 25.1+/-5.7% of attached cells transduced in these 1 week
      studies, with no detectable vector DNA in blood or distal organs. In vivo GFP
      expression was confirmed with immunohistochemistry. It is concluded that site
      specific intravascular delivery of adenoviral vectors for gene therapy can be
      achieved with polyurethane implants utilizing the antivector antibody tethering
      mechanism.

PMID- 14681694
TI  - Functional expression of ATM gene carried by HSV amplicon vector in vitro and in
      vivo.
AB  - Ataxia-telangiectasia (AT) is a human autosomal recessive disease with a
      pleiotropic phenotype characterized by cerebellar degeneration, immunodeficiency,
      premature aging, cancer predisposition, and radiation sensitivity. The gene
      mutated in AT, ATM (for AT-mutated), had been cloned and found to have ionizing
      radiation and oxidative stress-inducible kinase activity. No treatment can stop
      the progression of the disease. In this study, the complete open-reading frame of
      ATM cDNA was cloned into a Herpes simplex virus type-1 (HSV-1) amplicon vector
      (pTO-ATM), and the transduction of cultured AT cells was demonstrated by
      immunohistochemistry and Western blot analysis. Functional gene expression was
      evaluated by cell colony-forming assays following exposure to oxidative stress.
      The survival of AT cells with ATM gene transduction was about 100% higher
      compared to nontransduced cells after t-butyl hydroperoxide treatments. Next, the
      normal ATM gene expression in different regions of the rat brain was studied.
      Immunohistochemistry staining demonstrated weak endogenous ATM protein expression
      in neurons of the caudate-putamen, with significantly higher levels of expression
      detected in neurons in other brain regions. Exogenous ATM gene expression from
      pTO-ATM after viral transduction in the caudate-putamen of the adult rat was
      examined. At 3 days after injection of the pTO-ATM viral vector, abundant
      positive ATM staining of the neurons was found at the injection sites, in
      comparison to the controls. These data demonstrate that the relatively large ATM
      cDNA can be transduced and expressed in vitro and in vivo from an HSV amplicon
      viral vector. These data provide initial evidence that the replacement of the ATM
      gene into the cells of AT patients might be possible some day.

PMID- 14681695
TI  - Light-activated gene transduction of recombinant adeno-associated virus in human
      mesenchymal stem cells.
AB  - Deficiencies in skeletal tissue repair and regeneration lead to conditions like
      osteoarthritis, osteoporosis and degenerative disc disease. While no cure for
      these conditions is available, the use of human bone marrow derived-mesenchymal
      stem cells (HuMSCs) has been shown to have potential for cell-based therapy.
      Furthermore, recombinant adeno-associated viruses (rAAV) could be used together
      with HuMSCs for in vivo or ex vivo gene therapy. Unfortunately, the poor
      transduction efficiency of these cells remains a significant obstacle. Here, we
      describe the properties of ultraviolet (UV) light-activated gene transduction
      (LAGT) with rAAV in HuMSCs, an advance toward overcoming this limitation. Using
      direct fluorescent image analysis and real-time quantitative PCR to evaluate
      enhanced green fluorescent protein (eGFP) gene expression, we found that the
      optimal effects of LAGT with limited cytotoxicity occurred at a UV dose of 200
      J/m(2). Furthermore, this UV irradiation had no effect on either the chondrogenic
      or osteogenic potential of HuMSCs. Significant effects of LAGT in HuMSCs could be
      detected as early as 12 h after exposure and persisted over 21 days, in a time
      and energy-dependent manner. This LAGT effect was maintained for more than 8 h
      after irradiation and required only a 10-min exposure to rAAV after UV
      irradiation. Finally, we show that the production of secreted TGFbeta1 protein
      from rAAV-TGFbeta1-IRES-eGFP infected to HuMSCs is highly inducible by UV
      irradiation. These results demonstrate that LAGT combined with rAAV is a
      promising procedure to facilitate gene induction in HuMSCs for human gene
      therapy.

PMID- 14681696
TI  - Spontaneous transgenesis of human B lymphocytes.
AB  - DNA can cross the cell membrane by natural means, but the functional relevance of
      this phenomenon has not been fully elucidated. Here, we analyzed spontaneous
      transgenesis of human B cells using plasmid DNA coding for a functional
      immunoglobulin (Ig) heavy chain gene under the control of a B-cell-specific
      promoter. Using polymerase chain reaction (PCR), reverse transcriptase-PCR, and
      flow cytometry in combination, spontaneous transgenesis was documented in
      Burkitt's lymphoma cell lines, Epstein-Barr virus-transformed cell lines, and
      peripheral blood B lymphocytes of the mature naive phenotype (IgM(+)/IgD(+)/CD27(
      )). By immunoelectron microscopy, the internalized DNA was seen in the
      lysosomes/late endosomes and in the cytosol proximal to the nucleus. Importantly,
      spontaneously transgenic B cells processed and presented to major
      histocompatibility complex (MHC)-restricted T lymphocytes a peptide expressed in
      the transgenic product. This is the first demonstration that primary B
      lymphocytes possess a program for the spontaneous internalization of DNA, which
      in turn imparts the cell with new immunological functions. As spontaneous
      transgenesis is obtained using a nonviral vector, does not require prior cell
      activation, and is not associated with chromosomal integration, the findings
      reported here open new possibilities for genetic manipulations of mature naive B
      lymphocytes for therapy and vaccination.

PMID- 14681697
TI  - CMV enhancer/human PDGF-beta promoter for neuron-specific transgene expression.
AB  - Using cell-type-specific promoters to restrict expression of therapeutic genes to
      particular cells is an attractive approach for gene therapy, but often hindered
      by inefficient transcriptional activities of the promoters. Knowing the enhancer
      for the human cytomegalovirus (CMV) immediate-early gene improves activities of
      several cell-type- or tissue-type-specific promoters, we set out to investigate
      whether it improves neuronal transgene expression driven by a neuron-specific
      promoter, the platelet-derived growth factor B-chain (PDGF-beta) promoter. A
      hybrid promoter was constructed by appending a 380-bp fragment of the CMV
      enhancer 5' to the PDGF-beta promoter. The plasmid containing the promoter was
      complexed with polyethylenimine for in vitro and in vivo gene transfer. In
      cultured cells, the plasmid with the hybrid promoter significantly augmented
      expression of a luciferase reporter gene, providing expression levels 8- to 90
      fold and 7- to 178-fold higher than those from two baseline constructs containing
      the PDGF-beta promoter alone and the CMV enhancer alone, respectively. In
      particular, the activities of the hybrid promoter in two neural cell lines were
      close to or higher than that of the CMV immediate-early gene enhancer/promoter, a
      transcriptional control element that has been considered to be the most robust
      one identified thus far. After stereotaxic injection into the hippocampus and
      striatum in rats, the hybrid promoter displayed a neuronal specificity, driving
      gene expression almost exclusively in neurons. Transgene expression in the brain
      driven by the hybrid promoter was detectable 24 h after injection, being 10-fold
      higher than that driven by the PDGF-beta promoter alone. The expression peaked
      around 5 days at 1.5 x 10(5) relative light units per brain and lasted for at
      least 4 weeks. This differed strikingly from the expression driven by the PDGF
      beta promoter, which was no longer detectable on day 3. The new gene regulatory
      construct reported in this study will be useful to improve neuronal transgene
      expression required for gene therapy of neurological disorders and functional
      studies of the nervous system.

PMID- 14681698
TI  - SDF-1alpha/CXCL12 enhances retroviral-mediated gene transfer into immature
      subsets of human and murine hematopoietic progenitor cells.
AB  - Genetic modification of hematopoietic stem and progenitor cells has the potential
      to treat diseases affecting blood cells. Oncoretroviral vectors have been used
      for gene therapy; however, clinical success has been limited in part by low gene
      transfer efficiencies. We found that the presence of stromal-derived factor 1
      (SDF-1alpha)/CXCL12 during retroviral transduction significantly enhanced, in a
      dose-dependent fashion, gene transfer into immature subsets of high proliferative
      human and murine hematopoietic progenitor cells. Murine mononuclear bone marrow
      cells and purified c-Kit(+)Lin(-) bone marrow cells were prestimulated and
      transduced with the bicistronic retroviral vector MIEG3 on Retronectin-coated
      surfaces in the presence and absence of SDF-1. SDF-1 enhanced gene transduction
      of murine bone marrow and c-Kit(+)Lin(-) cells by 35 and 29%, respectively.
      Moreover, SDF-1 enhanced transduction of progenitors in these populations by 121
      and 107%, respectively. SDF-1 also enhanced transduction of human immature
      subsets of high proliferative progenitors present in either nonadherent
      mononuclear or CD34(+) umbilical cord blood cells. Transduction of hematopoietic
      progenitors was further increased by preloading Retronectin-coated plates with
      retrovirus using low-speed centrifugation followed by increasing cell-virus
      interactions through brief centrifugation during the transduction procedure.
      These results may be of clinical relevance.

PMID- 14681699
TI  - Widespread and efficient marker gene expression in the airway epithelia of fetal
      sheep after minimally invasive tracheal application of recombinant adenovirus in
      utero.
AB  - Cystic fibrosis is a common lethal genetic disease caused by functional absence
      of the cystic fibrosis transmembrane conductance regulator (CFTR). Although a
      candidate disease for in utero gene therapy, demonstration of potentially
      therapeutic levels of transgene expression in the fetal airways after minimally
      invasive gene delivery is a mandatory prerequisite before application of this
      approach in humans can be considered. We report here on the delivery of a beta
      galactosidase expressing adenovirus directly to the airways of fetal sheep in
      utero using ultrasound-guided percutaneous injection of the trachea in the fetal
      chest. Injection of adenoviral particles to the fetal airways was not associated
      with mortality and resulted in low-level expression in the peripheral airways.
      However, complexation of the virus with DEAE dextran, which confers a positive
      charge to the virus, and pretreatment of the airways with Na-caprate, which opens
      tight junctions, increased transgene expression, and a combination of these two
      enhancers resulted in widespread and efficient gene transfer of the fetal trachea
      and bronchial tree. Using a percutaneous ultrasound-guided injection technique,
      we have clearly demonstrated proof of principle for substantial transgene
      delivery to the fetal airways providing levels of gene expression that could be
      relevant for a therapeutic application of CFTR expressing vectors.

PMID- 14681700
TI  - Restoration of p53 tumor-suppressor activity in human tumor cells in vitro and in
      their xenografts in vivo by recombinant avian adenovirus CELO-p53.
AB  - Human adenovirus (Ad) vectors are extensively used as gene transfer vehicles.
      However, a serious obstacle for the use of these vectors in clinical applications
      is due to pre-existing immunity to human Ads affecting the efficacy of gene
      transfer. One of the approaches to circumvent host immune response could be the
      development of vectors based on non-human Ads that are able to transduce genes
      into human cells. In this study, we explored the possibility of using avian Ad
      CELO vectors as gene-transfer vehicles. For this purpose, we constructed a set of
      recombinant CELO viruses and demonstrated that they are able to deliver
      transgenes into various organs on the background of pre-existing immunity to
      human Ad5. The created CELO-p53 vector restored the function of the p53 tumor
      suppressor both in cultured human tumor cells in vitro and in their xenografts in
      nude mice in vivo. The latter effect was accompanied by inhibition of tumor
      growth. Noteworthily, the delivery of CELO-p53 led to activation of p53 target
      genes in cells showing inactivation of endogenous p53 by three different
      mechanisms, that is, in the human epidermoid carcinoma A431, lung adenocarcinoma
      H1299, and cervical carcinoma HeLa.

PMID- 14681701
TI  - Functional transfer of CD40L gene in human B-cell precursor ALL blasts by second
      generation SIN lentivectors.
AB  - Three different second-generation lentiviral self-inactivating vectors containing
      CMV, EF1alpha and PGK promoter, respectively, and all carrying the exogenous GFP
      gene, were compared for expression in human B-cell precursor ALL blasts. At a
      comparable percentage of transduction and vector DNA copy number, CMV clearly
      showed better efficiency of transcription. Human bone marrow stromal cells were
      favored compared to the MRC-5 cell line, as support for cell viability during
      infection. Cells were infected and analyzed after variable culture times ranging
      from 4 to 12 days, to reduce the possibility of pseudotransduction. In 10/14
      samples, we detected more than 20% GFP-positive cells after exposure to high
      titer viral supernatants. We then tested a similar vector carrying the human
      CD40L cDNA and, in similar infection conditions, obtained more than 20%
      transduction in 6/6 samples. The levels of transduction obtained were sufficient
      to induce the upregulation of CD83 molecule in cocultured immature dendritic
      cells.

PMID- 14681702
TI  - Engineering the splice acceptor for improved gene expression and viral titer in
      an MLV-based retroviral vector.
AB  - We have recently developed a retroviral vector that contains a splice acceptor
      from the human EF1-alpha gene and drives a significantly higher level of gene
      expression than other well known murine leukemia virus-based vectors. However,
      one downside of this vector is that viral titer significantly varies depending on
      the packaging lines used. Results from Northern blot analysis indicated that in
      certain cell lines the genomic transcript containing the packaging signal
      sequence was too efficiently spliced to the subgenomic RNA, resulting in low
      levels of genomic RNA and thus leading to a low viral titer. We tested the
      possibility of overcoming this problem by introducing mutations around the splice
      acceptor sequence in such a way that a delicate balance was maintained between
      the splicing efficiency (which determines the level of gene expression) and the
      amount of genomic transcript (which influences viral titer). After mutational
      analysis, one such mutant was found to meet this requirement. The newly
      constructed vector containing the engineered splice acceptor could indeed drive
      higher levels of expression in many therapeutic genes than other control vectors,
      without significantly compromising viral titer.

PMID- 14681703
TI  - Molecular strategies for improving cytokine transgene expression in normal and
      malignant tissues.
AB  - The augmentation and optimization of specific targeted transgene expression
      systems are important strategies for clinical research into gene therapy and DNA
      vaccination, due to safety considerations. In this study, we introduced 3'
      untranslated regions and transcriptional control modifications and direct tandem
      or combinational vector design strategies into a number of specific cytokine cDNA
      expression plasmids. The experiments were performed in parallel using both in
      vivo and in vitro transgene expression systems. In vivo studies were carried out
      using gene gun delivery of test vectors into mouse skin tissues. A combination of
      specific cell lines and fresh cell explants were used for in vitro and ex vivo
      transgene expression assay systems. The results from these comparative
      experiments demonstrated that a number of molecular biology manipulations can be
      readily adapted to define and significantly enhance the level or/and duration of
      transgene expression for a group of clinically relevant cytokine genes, with very
      similar effects for both in vivo and in vitro test systems. This cytokine
      transgene expression system may offer a favorable means for improving the
      efficiency of cytokine gene therapy and DNA vaccines in future clinical studies.

PMID- 14681704
TI  - CNS gene transfer mediated by a novel controlled release system based on DNA
      complexes of degradable polycation PPE-EA: a comparison with polyethylenimine/DNA
      complexes.
AB  - Nonviral gene delivery systems based upon polycation/plasmid DNA complexes are
      quickly gaining recognition as an alternative to viral gene vectors for their
      potential in avoiding immunogenicity and toxicity problems inherent in viral
      systems. We investigated in this study the feasibility of using a controlled
      release system based on DNA complexed with a recently developed polymeric gene
      carrier, polyaminoethyl propylene phosphate (PPE-EA), to achieve gene transfer in
      the brain. A unique feature of this gene delivery system is the biodegradability
      of PPE-EA, which can provide a sustained release of DNA at different rates
      depending on the charge ratio of the polymer to DNA. PPE-EA/DNA complexes, naked
      DNA, and DNA complexed with polyethylenimine (PEI), a nondegradable cationic
      polymer known to be an effective gene carrier, were injected intracisternally
      into the mouse cerebrospinal fluid. Transgene expression mediated by naked DNA
      was mainly detected in the brain stem, a region close to the injection site. With
      either PPE-EA or PEI as a carrier, higher levels of gene expression could be
      detected in the cerebral cortex, basal ganglia, and diencephalons. Transgene
      expression in the brain mediated by PPE-EA/DNA complexes at an N/P ratio of 2
      persisted for at least 4 weeks, with a significant higher level than that
      produced by either naked plasmid DNA or PEI/DNA at the 4-week time point.
      Furthermore, PPE-EA displayed much lower toxicity in cultured neural cells as
      compared to PEI and did not cause detectable pathological changes in the central
      nervous system (CNS). The results established the potential of PPE-EA as a new
      and biocompatible gene carrier to achieve sustained gene expression in the CNS.

PMID- 14681706
TI  - Effects of changes in water compartments on physiology and metabolism.
AB  - There is paramount evidence to suggest the importance of cell volume changes for
      the regulation of cell function, including protein metabolism. Among many other
      effects, cell swelling inhibits proteolysis and stimulates protein synthesis.
      However, most of the data pertinent to this theory relate to in vitro
      experiments. This paper reviews the evidence about the relevance of cell swelling
      and changes in water compartments to regulation of metabolism at the whole body
      level in animals and humans. Protein metabolism is most likely regulated by
      cellular hydration in health and disease. Cellular hydration appears to bear no
      effect on energy metabolism. The relationship between cellular hydration and
      lipolysis deserves to be verified. There appears to be a possible weak effect on
      glucose metabolism. Further studies are therefore necessary to challenge the cell
      swelling theory. If confirmed, strategies to modify cellular hydration could be
      used to improve metabolic orientations especially in the critically ill.

PMID- 14681707
TI  - Markers of hydration status.
AB  - Many indices have been investigated to establish their potential as markers of
      hydration status. Body mass changes, blood indices, urine indices and
      bioelectrical impedance analysis have been the most widely investigated. The
      current evidence and opinion tend to favour urine indices, and in particular
      urine osmolality, as the most promising marker available.

PMID- 14681708
TI  - 24-h hydration status: parameters, epidemiology and recommendations.
AB  - Hydration of individuals and groups is characterised by comparing actual urine
      osmolality (Uosm) with maximum Uosm. Data of actual, maximum and minimum Uosm in
      infants, children and adults and its major influencing factors are reviewed.
      There are remarkable ontogenetic, individual and cultural differences in Uosm. In
      the foetus and the breast-fed infant Uosm is much lower than plasma osmolality,
      whereas in children and adults it is usually much higher. Individuals and groups
      may show long-term differences in Uosm. In industrialised countries, the gender
      difference of Uosm is common. There are large intercultural differences of mean
      24-h Uosm ranging from 860 mosm/kg in Germany, 649 mosm/kg in USA to 392 mosm/kg
      in Poland. A new physiologically based concept called 'free-water reserve'
      quantifies differences in 24-h euhydration. In 189 boys of the DONALD Study aged
      4.0-6.9 y, median urine volume was 497 ml/24-h and median Uosm 809 mosm/kg.
      Considering mean-2 s.d. of actual maximum 24-h Uosm of 830 mosm/kg as upper level
      of euhydration and physiological criterion of adequate hydration in these boys,
      median free-water reserve was 11 ml/24-h. Based on median total water intake of
      1310 ml/24-h and the third percentile of free-water volume of -156 ml/24-h,
      adequate total water intake was 1466 ml/24-h or 1.01 ml/kcal. Data of Uosm in 24
      h urine samples and corresponding free-water reserve values of homogeneous groups
      of healthy subjects from all over the world might be useful parameters in
      epidemiology to investigate the health effects of different levels of 24-h
      euhydration.

PMID- 14681709
TI  - Impact of mild dehydration on wellness and on exercise performance.
AB  - Chronic mild dehydration is a common condition in some population groups,
      including especially the elderly and those who participate in physical activity
      in warm environments. Hypohydration is recognised as a precipitating factor in a
      number of acute medical conditions in the elderly, and there may be an
      association, although not necessarily a causal one, between a low habitual fluid
      intake and some cancers, cardiovascular disease and diabetes. There is some
      evidence of impairments of cognitive function at moderate levels of
      hypohydration, but even short periods of fluid restriction, leading to a loss of
      body mass of 1-2%, lead to reductions in the subjective perception of alertness
      and ability to concentrate and to increases in self-reported tiredness and
      headache. In exercise lasting more than a few minutes, hypohydration clearly
      impairs performance capacity, but muscle strength appears to be relatively
      unaffected.

PMID- 14681710
TI  - Impaired cognitive function and mental performance in mild dehydration.
AB  - Dehydration is a reliable predictor of impaired cognitive status. Objective data,
      using tests of cortical function, support the deterioration of mental performance
      in mildly dehydrated younger adults. Dehydration frequently results in delirium
      as a manifestation of cognitive dysfunction. Although, the occurrence of delirium
      suggests transient acute global cerebral dysfunction, cognitive impairment may
      not be completely reversible. Animal studies have identified neuronal
      mitochondrial damage and glutamate hypertransmission in dehydrated rats.
      Additional studies have identified an increase in cerebral nicotinamide adenine
      dinucleotide phosphate-diaphorase activity (nitric oxide synthase, NOS) with
      dehydration. Available evidence also implicates NOS as a neurotransmitter in long
      term potentiation, rendering this a critical enzyme in facilitating learning and
      memory. With ageing, a reduction of NOS activity has been identified in the
      cortex and striatum of rats. The reduction of NOs synthase activity that occurs
      with ageing may blunt the rise that occurs with dehydration, and possibly
      interfere with memory processing and cognitive function. Dehydration has been
      shown to be a reliable predictor of increasing frailty, deteriorating mental
      performance and poor quality of life. Intervention models directed toward
      improving outcomes in dehydration must incorporate strategies to enhance prompt
      recognition of cognitive dysfunction.

PMID- 14681711
TI  - Effects on health of fluid restriction during fasting in Ramadan.
AB  - During the 9th month (Ramadan) of the Islamic calendar (Hijra) many millions of
      adult Muslims all over the world fast during the daylight hours. Since Hijra is a
      lunar calendar, Ramadan occurs at different times in the seasonal year over a 33
      year cycle. Fasting during Ramadan is partial because the abstention from food,
      fluid, tobacco and caffeine is from sunrise to sunset. Several categories of
      people are exempt or can postpone the Ramadan fast. The effect on health and well
      being of the month-long intermittent fast and fluid restriction has been studied
      in various potentially vulnerable groups in addition to normal healthy
      individuals in many countries. The majority of the studies have found significant
      metabolic changes, but few health problems arising from the fast. A reduction in
      drug compliance was an inherent negative aspect of the fast. Common findings of
      the studies reviewed were increased irritability and incidences of headaches with
      sleep deprivation and lassitude prevalent. A small body mass loss is a frequent,
      but not universal, outcome of Ramadan. During the daylight hours of Ramadan
      fasting, practising Muslims are undoubtedly dehydrating, but it is not clear
      whether they are chronically hypohydrated during the month of Ramadan. No
      detrimental effects on health have as yet been directly attributed to negative
      water balance at the levels that may be produced during Ramadan.

PMID- 14681712
TI  - Mild dehydration, vasopressin and the kidney: animal and human studies.
AB  - Water balance depends essentially on fluid intake and urine excretion. Mild
      dehydration and the consequent hypertonicity of the extracellular fluid induce an
      increase in vasopressin secretion, thus stimulating urine concentrating processes
      and the feeling of thirst. The osmotic threshold for the release of vasopressin
      is lower than that for thirst and also shows appreciable individual variation.
      Sustained high levels of vasopressin and low hydration induce morphological and
      functional changes in the kidney. However, they could also be risk factors in
      several renal disorders, such as chronic renal failure, diabetic nephropathy and
      salt-sensitive hypertension.

PMID- 14681713
TI  - Fluid intake and epidemiology of urolithiasis.
AB  - A low urine volume is an important risk factor in urinary stone formation. The
      present article summarizes available data from epidemiological and clinical
      studies to elucidate the impact of fluid intake and urine volume on the risk of
      urinary stone formation and the prevention of stone recurrence. A review of the
      literature shows that an increased urine volume achieved by a high fluid intake
      exerts an efficacious preventive effect on the onset and recurrence of urinary
      stones. A high water intake and urine dilution results in a marked reduction in
      saturation of lithogenous salts. The type of fluids should be carefully selected
      to achieve the appropriate change of urine composition depending on stone
      composition. A sufficient intake of fluid is one of the most important preventive
      measures for stone recurrence.

PMID- 14681714
TI  - Mild dehydration: a risk factor of urinary tract infection?
AB  - Bacterial growth in the urinary tract is usually prevented by host factors
      including bacterial eradication by urinary and mucus flow, urothelial
      bactericidal activity, urinary secretory IgA, and blood group antigens in
      secretions which interfere with bacterial adherence. Bacterial eradication from
      the urinary tract is partially dependent on urine flow and voiding frequency.
      Therefore, it seems logical to postulate a connection between fluid intake and
      the risk of urinary tract infections (UTIs). However, experimental and clinical
      data on this subject are conflicting. Experimental studies concerning the effect
      of water intake on susceptibility and course of UTIs were predominantly performed
      in the 60s and 70s. Despite many open questions, there has been no continuous
      research in this field. Only few clinical studies producing contradictory results
      are available on the influence of fluid intake concerning the risk of UTI. One
      explanation for the inconsistency between the data might be the uncertainty about
      the exact amounts of fluid intake, which was mostly recorded in questionnaires.
      So far, there is no definitive evidence that the susceptibility for UTI is
      dependent on fluid intake. Nevertheless, adequate hydration is important and may
      improve the results of antimicrobial therapy in UTI. Results of experimental and
      clinical studies concerning urinary hydrodynamics are the basis for advice given
      by expert committees to patients with UTI to drink large volumes of fluid, void
      frequently, and completely empty the bladder. The combination of the
      behaviourally determined aspects of host defence and not simply increasing fluid
      intake is important in therapy and prophylaxis of UTI.

PMID- 14681715
TI  - Fluid intake and risk of bladder and other cancers.
AB  - There are appreciable differences in total fluid intake at the individual and
      population level, and substantial difficulties in obtaining valid measures of
      fluid intake. Epidemiological studies have examined the association between fluid
      intake and different types of cancer. For bladder cancer, fluid consumption has
      been associated with a moderate increase of risk in some studies, including a
      multicentric case-control study from the United States, based on about 3000
      cases, with a decrease in others, including the Health Professional Follow-up
      study, or with no material association. The evidence, therefore, is far from
      consistent. Sources and components of fluids were also different across different
      types studies. From a biological point of view, a decreased fluid intake could
      result in a greater concentration of carcinogens in the urine or in a prolonged
      time of contact with the bladder mucosa because of less frequent micturition.
      Carcinogenic or anticarcinogenic components of various beverages excreted in the
      urine may also play a role in the process. It has been suggested that fluid
      consumption has a favorable effect on colorectal cancer risk. Fluid intake may
      reduce colon cancer risk by decreasing bowel transit time and reducing mucosal
      contact with carcinogens. Low fluid intake may also compromise cellular
      concentration, affect enzyme activity in metabolic regulation, and inhibit
      carcinogen removal. However, epidemiological data are inadequate for evaluation.
      Data are sparse and inconsistent for other neoplasms, including breast cancer.
      The fluid constituent of foods, confounding, interactions and possible influences
      of specific types of beverages should be investigated further. In conclusion
      therefore the association between total fluid intake and cancer risk remains
      still open to debate.

PMID- 14681716
TI  - Effects of changes in hydration on protein, glucose and lipid metabolism in man:
      impact on health.
AB  - Alterations of cell volume induced by changes of extracellular osmolality have
      been reported to regulate intracellular metabolic pathways. Hypo-osmotic cell
      swelling counteracts proteolysis and glycogen breakdown in the liver, whereas
      hyperosmotic cell shrinkage promotes protein breakdown, glycolysis and
      glycogenolysis. To investigate the effect of acute changes of extracellular
      osmolality on whole-body protein, glucose and lipid metabolism in vivo, we
      studied 10 male subjects during three conditions: (i) hyperosmolality was induced
      by fluid restriction and intravenous infusion of hypertonic NaCl (2-5%, wt/vol)
      during 17 h; (ii) hypo-osmolality was produced by intravenous administration of
      desmopressin, liberal water drinking and infusion of hypotonic saline (0.4%); and
      (iii) the iso-osmolality study comprised oral water intake ad libitum. Plasma
      osmolality increased from 285+/-1 to 296+/-1 mosm/kg (P<0.001 during
      hyperosmolality, and decreased from 286+/-1 to 265+/-1 mosm/kg during hypo
      osmolality (P<0.001). Total body leucine flux ([1-(13)C]leucine infusion
      technique), reflecting whole-body protein breakdown, as well as whole-body
      leucine oxidation rate (irreversible loss of amino acids) decreased significantly
      during hypo-osmolality. The glucose metabolic clearance rate during
      hyperinsulinaemic-euglycemic clamping increased significantly less during hypo
      osmolality than iso-osmolality, indicating diminished peripheral insulin
      sensitivity. Glycerol turnover (2-[(13)C]glycerol infusion technique), reflecting
      whole-body lipolysis, increased significantly during hypo-osmolar conditions. The
      results demonstrate that the metabolic adaptation to acute hypo-osmolality
      resembles that of acute fasting, that is, it results in protein sparing
      associated with increased lipolysis, ketogenesis and lipid oxidation and impaired
      insulin sensitivity of glucose metabolism.

PMID- 14681717
TI  - Mild dehydration: a risk factor for dental disease?
AB  - A review of the published international literature was undertaken to investigate
      whether dehydration is a risk factor for dental disease. Published evidence of
      associations between saliva and dental disease and between saliva and dehydration
      was observed, but the precise nature of these associations is unclear and no
      evidence of a direct link between dehydration and dental disease was found. It is
      concluded that no direct link between dehydration and dental disease has been
      proven, although there is considerable circumstantial evidence to indicate that
      such a link exists.

PMID- 14681718
TI  - Mild dehydration: a risk factor of broncho-pulmonary disorders?
AB  - Several expert committees recommend a high fluid intake in patients with chronic
      bronchitis and asthma. Is there a relationship between fluid intake or hydration
      status and broncho-pulmonary disorders like bronchitis and asthma? First, basic
      physiologic mechanisms like regulation of lung fluid balance and water transport
      at pulmonary surfaces were analyzed, in order to characterize the role of local
      hydration status in lung and airways. Second, making use of the computer-based
      literature searches (PubMed), evidence for a role of hydration status in complex
      physiological and pathophysiological conditions of lungs and airways like
      perinatal lung adaptation (PLA) (in prematures), mucociliary clearance(MC) and
      asthma was categorized. The movement of fluid between the airspaces,
      interstitium, and vascular compartments in the lungs plays an important
      physiological role in the maintenance of hydration and protection of the lung
      epithelium and significantly contributes to a proper airway clearance. PLA is
      characterized by a rapid change from fluid secretion to fluid absorption in the
      distal respiratory tract, with the literature data confirming a critical role of
      the epithelial sodium channel. Only few studies have investigated the effect of
      different fluid input regimens on PLA in prematures. MC relies on the interaction
      between epithelial water fluxes, mucus secretions, and ciliary activity. Whereas
      animal data show that drying of the airway epithelium decreases MC, few clinical
      studies investigating the effect of local or systemic hydration on MC have led to
      ambiguous results. Asthma (A) is characterized by chronic airway inflammation and
      episodic airway obstruction. Data in animals and humans indicate an association
      between exercise-induced-A and conditioning (humidity and heat exchange) of
      inspired air. However, epidemiological studies (children and adults),
      investigating the role of fluid (and salt) input in the etiology of the disease
      as well as studies analyzing different markers of hydration status during
      asthmatic attacks have so far led to conflicting results. Some expert groups
      recommend sufficient hydration as a complementary A-therapy. Analysis of basic
      physiological mechanisms in lungs and airways clearly demonstrates a critical
      role for water transport and local hydration status. In broncho-pulmonary
      diseases, however, analysis of the complex pathophysiological mechanisms is
      difficult. Thus, we still need more studies to confirm or refute mild dehydration
      or hypohydration as a risk factor of broncho-pulmonary disorders.

PMID- 14681719
TI  - Mild dehydration: a risk factor of constipation?
AB  - Constipation defined as changes in the frequency, volume, weight, consistency and
      ease of passage of the stool occurs in any age group. The most important factors
      known to promote constipation are reduced physical activity and inadequate
      dietary intake of fibres, carbohydrates and fluids. Fluid losses induced by
      diarrhoea and febrile illness alter water balance and promote constipation. When
      children increase their water consumption above their usual intake, no change in
      stool frequency and consistency was observed. The improvement of constipation by
      increasing water intake, therefore, may be effective in children only when
      voluntary fluid consumption is lower-than-normal for the child's age and activity
      level. In the elderly, low fluid intake, which may be indicative of
      hypohydration, was a cause of constipation and a significant relationship between
      liquid deprivation from 2500 to 500 ml per day and constipation was reported.
      Dehydration is also observed when saline laxatives are used for the treatment of
      constipation if fluid replacement is not maintained and may affect the efficacy
      of the treatment. While sulphate in drinking water does not appear to have a
      significant laxative effect, fluid intake and magnesium sulphate-rich mineral
      waters were shown to improve constipation in healthy infants. In conclusion,
      fluid loss and fluid restriction and thus de-or hypohydration increase
      constipation. It is thus important to maintain euhydration as a prevention of
      constipation.

PMID- 14681720
TI  - Summary and outlook.

PMID- 14681721
TI  - hTERT-promoter-based tumor-specific expression of MCP-1 effectively sensitizes
      cervical cancer cells to a low dose of cisplatin.
AB  - Cervical cancers at advanced stages or with recurrent status are mainly treated
      by platinum-based chemotherapy, such as cisplatin. However, a novel strategy to
      reduce the minimally effective dose is required to prevent severe adverse effects
      that limit the effectiveness of the treatment. Monocyte chemoattractant protein-1
      (MCP-1) is a subtype of chemokines that can promote monocyte/macrophage
      infiltration and enhance their phagocytosis at not only sites of inflammatory
      lesions but also of tumors. The present study applies MCP-1-based gene therapy to
      treat cervical cancers. To achieve tumor-specific expression of MCP-1, retroviral
      expression vector was constructed using the human telomerase reverse
      transcriptase gene (hTERT) promoter. Retroviral expression of MCP-1 into cervical
      cancer ME180 cells did not affect their proliferation either in vitro or in vivo.
      However, when combined with a suboptimal low dose of cisplatin, tumor formation
      was obviously reduced in clones transduced with MCP-1, but not in control clones.
      Histological examination revealed that a substantial number of macrophages
      infiltrated the tumor sites of MCP-1-transduced cells, but not of controls. These
      findings suggest that MCP-1 expression sensitizes cervical cancer cells to an
      otherwise ineffective low dose of cisplatin, possibly by inducing the migration
      of macrophages to eradicate tumor cells. This system may be a novel strategy for
      chemotherapy combined with immunogene therapy against otherwise intractable
      cervical cancers.

PMID- 14681722
TI  - Adenovirus-mediated tumor-specific combined gene therapy using Herpes simplex
      virus thymidine/ganciclovir system and murine interleukin-12 induces effective
      antitumor activity against medullary thyroid carcinoma.
AB  - The present treatment of advanced and metastatic medullary thyroid carcinoma
      (MTC) is unsatisfactory. Tissue-specific cancer gene therapy is a novel
      alternative approach. We developed a recombinant adenovirus expressing Herpes
      simplex type 1 thymidine kinase (HSVtk) driven by a modified CALC-I promoter TCP
      (AdTCPtk). Infection with this virus showed efficient cytotoxic effect on MTC
      cell lines (rMTC and TT cells) after treatment with ganciclovir (GCV) in vitro.
      In a syngenic WAG/Rij rat model, the combination of AdTCPtk/GCV treatment with
      administration of murine interleukin-12 (mIL-12) expressing adenovirus under
      control of TCP (AdTCPmIL-12) resulted in effective growth suppression of tumor at
      the treated site and also at a distant untreated site, in comparison to treatment
      with AdTCPtk/GCV or AdTCPmIL-12 alone. Moreover, intravenous injection of
      AdTCPtk, or AdTCPtk+AdTCPmIL-12, followed by administration of GCV, did not cause
      evident toxicity after administration of GCV. These results indicate that this
      combined system can provide an effective therapy for metastatic MTC with minimal
      toxicity.

PMID- 14681723
TI  - Combined suicide gene therapy for pancreatic peritoneal carcinomatosis using BGTC
      liposomes.
AB  - Peritoneal dissemination is a common end-stage complication of pancreatic cancer
      for which novel therapeutic modalities are actively investigated, as there is no
      current effective therapy. Thus, we evaluated, in a mouse model of pancreatic
      peritoneal carcinomatosis, the therapeutic potential of a novel nonviral gene
      therapy approach consisting of bis-guanidinium-tren-cholesterol (BGTC)-mediated
      lipofection of a combined suicide gene system. Human BxPC-3 pancreatic cells
      secreting the carcinoembryonic antigen (CEA) tumor marker were injected into the
      peritoneal cavity of nude mice. After 8 days, intraperitoneal (i.p.) lipofection
      was performed using BGTC/DOPE cationic liposomes complexed with plasmids encoding
      the two prodrug-activating enzymes Herpes Simplex Virus thymidine kinase and
      Escherichia coli cytosine deaminase, the latter being expressed from a
      bicistronic cassette also encoding E. coli uracil phosphoribosyltransferase.
      Administration of the lipoplexes was followed by treatment with the corresponding
      prodrugs ganciclovir and 5-fluorocytosine. The results presented herein
      demonstrate that BGTC/DOPE liposomes can efficiently mediate gene transfection
      into peritoneal tumor nodules. Indeed, HSV-TK mRNA was detected in tumor nodule
      tissues by semiquantitative reverse transcription-polymerase chain reaction
      analysis. In addition, green fluorescent protein (GFP) fluorescence and X-gal
      staining were observed in the peritoneal tumor foci following lipofection of the
      corresponding EGFP and LacZ reporter genes. These expression analyses also showed
      that transgene expression lasted for about 2 weeks and was preferential for the
      tumor nodules, this tumor preference being in good agreement with the absence of
      obvious treatment-related toxicity. Most importantly, mice receiving the full
      treatment scheme (BGTC liposomes, suicide genes and prodrugs) had significantly
      lower serum CEA levels than those of the various control groups, a finding
      indicating that peritoneal carcinomatosis progression was strongly reduced in
      these mice. In conclusion, our results demonstrate the therapeutic efficiency of
      BGTC-mediated i.p. lipofection of a combined suicide gene system in a mouse
      peritoneal carcinomatosis model and suggest that BGTC-based prodrug-activating
      gene therapy approaches may constitute a potential treatment modality for
      patients with peritoneal carcinomatosis and minimal residual disease.

PMID- 14681724
TI  - Tumor-specific adenoviral gene therapy: transcriptional repression of gene
      expression by utilizing p53-signal transduction pathways.
AB  - Adenoviral gene expression that is repressed by p53 in nontransformed cells could
      provide a tumor-specific gene therapy approach for a large subset of tumors.
      Adenoviral infection in vivo induces stabilization of p53, which can be utilized
      for a strategy that includes p53-dependent expression of a transcriptional
      repressor and a target promoter,which is highly susceptible for transcriptional
      repression. Therefore, we constructed different versions of CMV-promoters
      (CMVgal) with binding sites for GAL4-DBD and investigated 11 GAL4-DBD fusion
      proteins to elucidate the most effective repressor domain to silence CMVgal
      activity. The transcriptional repressor GAL4-KRAB-A under control of a p53
      dependent promoter facilitates strong CMVgal-mediated gene expression
      specifically in p53 mutant cells by a double-recombinant adenoviral vector (Ad
      RGCdR). GAL4-KRAB-A mediates strong transcriptional repression of Ad-RGCdR in p53
      wild-type cells, which could be further enhanced by preactivation of p53
      signalling following low-dose chemotherapy prior to adenoviral infection. By
      utilizing p53 signalling involved in chemotherapy and adenoviral infection, more
      than 99% of Ad-RGCdR gene expression could be repressed in p53 wild-type cells.
      Controlled gene expression from CMVgal promoters by transcriptional repression
      utilizing functional p53 signalling thus provides a very effective tool for tumor
      specific adenoviral gene therapy.

PMID- 14681725
TI  - Tumor-specific gene expression using regulatory elements of the glucose
      transporter isoform 1 gene.
AB  - In order to achieve tumor-specific targeting of adeno-associated virus (AAV)
      mediated gene expression, the promoter of the glucose transporter isoform 1
      (GLUT1) gene was cloned upstream of the enhanced green fluorescence protein
      (EGFP) and the herpes simplex virus thymidine kinase (HSVtk) gene. FACS analysis
      performed at 48 h after transient infection with rAAV/cytomegalovirus (CMV)egfp
      viral particles revealed an increase of fluorescence in all the cell lines
      tested. However, EGFP expression under control of the GLUT1 promoter element
      (rAAV/GTI-1.3egfp) was limited to the tumor cells and oncogene-transformed cells.
      Evidence for phosphorylation of the HSVtk substrates ganciclovir (GCV) and 125I
      deoxycytidine was found in all transfected tumor cell lines compared to
      noninfected controls (HCT116: 111%; MH3924A: 130%; HaCaT-RT3: 257% increase), but
      not in HaCaT and HUVEC cells. Furthermore, tumor cells and the oncogene
      transformed (ras) cell line HaCaT-RT3 showed a GCV-induced reduction in cell
      number (HCT116: -71%; MH3924A: -43% and HaCaT-RT3: -31%). No statistically
      relevant cytotoxic effect was observed in HaCaT (6% decrease) and HUVEC cells (2%
      decrease). Furthermore, a reduction of 3H-thymidine incorporation into the DNA
      was seen after treatment with GCV (HCT116: 38%; MH3924A: 33% and HaCaT-RT3: 37%
      decrease). In a therapy study of HSVtk-expressing tumors with GCV, we achieved
      total tumor remission.

PMID- 14681726
TI  - Kinase-dead PKB gene therapy combined with hyperthermia for human breast cancer.
AB  - We have previously demonstrated that protein kinase B (PKB) is a mediator of heat
      induced apoptosis for human breast cancer cells. To investigate the therapeutic
      potential of abrogating the function of this important survival protein, a novel
      replication-deficient adenovirus was constructed, wherein a mutant, kinase
      inactive PKB gene (AAA) was inserted downstream of the CMV promoter. Two human
      breast cancer cell lines, MCF-7 and MDA-468, were treated, along with the MCF-10
      serving as a "normal" mammary epithelial comparator. Apoptosis was increased with
      adv.AAA (25 PFU/cell) infection alone, but was significantly enhanced with the
      addition of heat exposure. Differential survival was observed with the MDA-468
      cancer cells being more sensitive than the MCF-7 cells. The MCF-10 cells, in
      contrast, were most resistant to these treatments. Results from the clonogenic
      assay reflected the apoptosis data, with an apparent additive interaction between
      adv.AAA and hyperthermia treatments, again with greater differential sensitivity
      of the malignant, compared to the "normal" mammary epithelial cells. Heat or
      adv.beta-gal treatments led to phosphorylation of PKB and Forkhead, but this
      phosphorylation was reduced with adv.AAA therapy. In parallel, the combination of
      adv.AAA and heat treatment reduced PKB kinase activity more so than with either
      heat or adv.beta-gal alone. In conclusion, our results demonstrate that
      inhibition of the PKB-dependent survival pathway will promote apoptosis and
      thermosensitization in malignant breast cancer cells, with relative sparing of
      their normal counterpart, suggesting that a therapeutic gain could be achievable
      using this therapeutic strategy.

PMID- 14681727
TI  - Tumor irradiation followed by intratumoral cytokine gene therapy for murine renal
      adenocarcinoma.
AB  - To circumvent the toxicity caused by systemic injection of cytokines, cytokine
      cDNA genes encoding the human interleukin IL-2 cDNA (Ad-IL-2) and murine
      interferon IFN-gamma gene (Ad- IFN-gamma) were inserted into adenoviral vectors.
      These constructs were used for intratumoral gene therapy of murine renal
      adenocarcinoma Renca tumors. Treatment with three doses of Ad-IL-2 or Ad- IFN
      gamma, given a day apart, was more effective than single-dose gene therapy. We
      found that tumor irradiation enhanced the therapeutic efficacy of Ad-IL-2 and Ad
      IFN-gamma intratumoral gene therapy. Tumor irradiation, administered 1 day prior
      to three doses of Ad-IL-2 treatment, was more effective than radiation or Ad-IL-2
      alone, resulting in tumor growth arrest in all mice, increased survival and a
      consistent increase in complete tumor regression response rate. Complete
      responders rejected Renca tumor challenge and demonstrated specific cytotoxic T
      cell activity, indicative of specific tumor immunity. The effect of radiation
      combined with three doses of Ad-IFN-gamma was less pronounced and did not lead to
      tumor immunity. Histological observations showed that irradiation of the tumor
      prior to gene therapy increased tumor destruction and inflammatory infiltrates in
      the tumor nodules. These findings demonstrate that tumor irradiation improves the
      efficacy of Ad-IL-2 gene therapy for induction of antitumor immune response.

PMID- 14681728
TI  - AAV-mediated gene transfer of tissue inhibitor of metalloproteinases-1 inhibits
      vascular tumor growth and angiogenesis in vivo.
AB  - The activity of matrix metalloproteinases (MMPs) is a universal feature of
      cellular invasion, tumor angiogenesis and metastasis, which is counterbalanced
      and regulated by the natural tissue inhibitors of MMPs (Timps). Here we show that
      Timp1 gene transfer delivered by an adeno-associated virus (AAV) vector inhibits
      tumor growth in a murine xenotransplant model. A human Kaposi's sarcoma cell
      line, forming highly vascularized tumors in vivo and having a high natural
      permissivity to AAV gene transfer, was transduced to express the Timp1 cDNA. AAV
      Timp1-transduced cells secreted high levels of Timp1 that inhibited MMP2 and MMP9
      gelatinolytic activity. Following subcutaneous inoculation in nude mice, the AAV
      Timp1-transduced cells showed significantly reduced tumor growth when compared to
      control AAV-LacZ-transduced cells. In addition, direct intratumoral injection of
      AAV-Timp1 into pre-existing tumors significantly impaired the further expansion
      of the tumor mass. Histological analyses showed that the AAV-Timp1-transduced
      tumors had limited development of vascular structures and extensive areas of cell
      death, suggesting that Timp1 overexpression had an antiangiogenic effect. To
      further support this conclusion, we demonstrated that AAV-Timp1 transduction
      significantly reduced endothelial cell migration and the invasion of a Matrigel
      barrier and strongly inhibited angiogenesis in the chick chorioallantoic membrane
      assay. These results indicate that transfer and overexpression of the Timp1 gene
      is a promising therapeutic strategy to target tumor-associated angiogenesis in
      cancer gene therapy.

PMID- 14681736
TI  - Chironomid egg masses as a natural reservoir of Vibrio cholerae non-O1 and non
      O139 in freshwater habitats.
AB  - Cholera is a diarrheal disease caused by the gram-negative bacterium Vibrio
      cholerae, and an estimated 120,000 deaths from cholera occur globally every year.
      The natural reservoir of the bacterium is environmental. A recent report
      indicated an association between V. cholerae and chironomid egg masses.
      Chironomids, the "non-biting midges" (Diptera; Chironomidae), are the most widely
      distributed and frequently the most abundant insects in freshwater. Females
      attach egg masses, each containing hundreds of eggs encased in a layer of
      gelatin, to the water's edge where bacteria are abundant and may encounter the
      nutrient-rich substrate. Here we report the isolation of non-O1 and non-O139 V.
      cholerae from chironomid egg masses from different freshwater bodies in Israel,
      India, and Africa. In a yearly survey in Israel, chironomid populations were
      found to peak biannually, and it seemed that those peaks were followed by
      subsequent bacterial growth and disappearance during the winter in the
      Mediterranean region. The bacterial population rose as water temperature
      surpassed 25 degrees C. Thirty-five different serogroups of V. cholerae were
      identified among the bacteria isolated from chironomids, demonstrating population
      heterogeneity. Two strains of V. cholerae O37 and O201 that were isolated from
      chironomid egg masses in Zanzibar Island were NAG-ST positive. Our findings
      support the hypothesis that the association found between chironomids and the
      cholera bacteria is not a rare coincidence, indicating that chironomid egg masses
      may serve as yet another potential reservoir for V. cholerae.

PMID- 14681737
TI  - Associations of cyanobacterial toxin, nodularin, with environmental factors and
      zooplankton in the Baltic Sea.
AB  - Concentrations of a cyanobacterial toxin, nodularin, were measured in the Baltic
      Sea in 1998 and 1999. Statistical associations of nodularin concentrations with
      environmental factors were tested by multiple regression analysis. To reveal the
      toxin-producing organism, colonies of Aphanizomenon and filaments of Nodularia
      were picked and analyzed for peptide toxins. It was also investigated whether
      there was an association with zooplankton and Nodularia. All the measured seston
      samples contained nodularin, but other toxins were not detected by the HPLC
      analysis. In both years, the highest nodularin concentrations were found at the
      surface water layer. The nodularin concentrations were positively correlated with
      silicate concentrations in water. High concentrations of silica in surface water
      may indicate recent upwelling, which in turn renders surface water rich in
      nutrients. This upwelling is likely to intensify cyanobacterial growth and toxin
      production, which may explain this rather unexpected result. The picked
      Aphanizomenon colonies did not contain nodularin and the dissolved nodularin
      concentrations were below detection limit. Thus it was concluded that most of the
      nodularin was bound to Nodularia cells. The abundances of zooplankton (copepods,
      rotifers, and cladocerans) were unrelated to Nodularia, but were positively
      associated with Aphanizomenon.

PMID- 14681738
TI  - Biofilm structure and function and possible implications for riverine DOC
      dynamics.
AB  - Biofilms are major sites of carbon cycling in streams and rivers. Here we
      elucidate the relationship between biofilm structure and function and river DOC
      dynamics. Metabolism (extracellular enzymatic activity) and structure (algae,
      bacteria, C/N content) of light-grown (in an open channel) and dark-grown (in a
      dark pipe) biofilms were studied over a year, and variations in dissolved organic
      carbon (DOC) and biodegradable DOC (BDOC) were also recorded. A laboratory
      experiment on 14C-glucose uptake and DOC dynamics was also performed by
      incubating natural biofilms in microcosms. On the basis of our field (annual DOC
      budget) and laboratory results, we conclude that light-grown biofilm is, on
      annual average, a net DOC consumer. This biofilm showed a high monthly
      variability in DOC uptake/release rates, but, on average, the annual uptake rate
      was greater than that of the dark-grown biofilm. The higher algal biomass and
      greater structure of the light-grown biofilm may enhance the development of the
      bacterial community (bacterial biomass and activity) and microbial heterotrophic
      activity. In addition, the light-grown biofilm may promote abiotic adsorption
      because of the development of a polysaccharide matrix. In contrast, the dark
      grown biofilm is highly dependent on the amount and quality of organic matter
      that enters the system and is more efficient in the uptake of labile molecules
      (higher 14C-glucose uptake rate per mgC). The positive relationships between the
      extracellular enzymatic activity of biofilm and DOC and BDOC content in flowing
      water indicate that biofilm metabolism contributes to DOC dynamics in fluvial
      systems. Our results show that short-term fluvial DOC dynamics is mainly due to
      the use and recycling of the more labile molecules. At the river ecosystem level,
      the potential surface area for biofilm formation and the quantity and quality of
      available organic carbon might determine the effects of biofilm function on DOC
      dynamics.

PMID- 14681739
TI  - Biostimulation of natural microbial assemblages in oil-amended vegetated and
      desert sub-Antarctic soils.
AB  - A field study was initiated in December 2000 in two selected soils of The Grande
      Terre (Kerguelen Archipelago) with the objective of determining the long-term
      effects of fertilizer addition on the biodegradation rate and the toxicity of oil
      residues under severe sub-Antarctic conditions. Two soils were selected. The
      first site supports an abundant vegetal cover; the second one was desert soil,
      devoid of plant material. These two soils were located in the vicinity of the
      permanent station of Port-aux-Francais (69 degrees 42'E; 49 degrees 19'S). A
      series of five experimental plots (0.75 x 0.75 m) were settled firmly into each
      of the studied soils. Each plot received 500 mL of diesel or Arabian light crude
      oil, and some of them were treated with a bioremediation agent: slow-release
      fertilizer Inipol EAP-22 (Elf Atochem). All the plots were sampled on a regular
      basis over a 1 year period. Heterotrophic and hydrocarbon-degrading
      microorganisms increased by two orders of magnitude during the first month of the
      experimentation in all treated enclosures, but differences appeared between the
      different plots. The microbial response was improved by bioremediation
      treatments. However, fertilizer addition had a greater impact on the desert soil
      when compared to the vegetated one. All chemical indices show a reduction of
      alkanes and light aromatics. Toxicity results show a high variability between
      treatments and environmental conditions. As a conclusion, it is clear that the
      microbial response was rapid and efficient in spite of the severe weather
      conditions, and the rate of degradation was improved by bioremediation
      treatments. However, after 1 year of treatment, the signal of a relatively high
      toxicity of oiled residues remained present in the two studied soils.

PMID- 14681740
TI  - Neonatal intractable atrial flutter successfully treated with intravenous
      flecainide.
AB  - We present a neonatal case with intractable atrial flutter that did not respond
      to digitalization and electrical cardioversion. Intravenous flecainide
      administration completely resolved the atrial flutter. Proarrhythmic effects were
      not induced by flecainide administration. Although the efficacy of flecainide for
      atrial flutter during the infantile or childhood period is low, intravenous
      flecainide is worth consideration as a treatment for atrial flutter, even in
      intractable cases as described here, during the neonatal period.

PMID- 14681742
TI  - [Meeting of the Section for Pathophysiology and Aerosol Medicine of the German
      Society of Pneumology].

PMID- 14681741
TI  - Comparison between cardiac output measured by the pulmonary arterial
      thermodilution technique and that measured by the femoral arterial thermodilution
      technique in a pediatric animal model.
AB  - This study compares the correlation between two methods for the determination of
      cardiac output-the pulmonary arterial thermodilution technique using the Swan
      Ganz catheter and the femoral arterial thermodilution technique using a pulse
      contour analysis computer (PiCCO) catheter. We performed a prospective animal
      study using 16 immature Maryland pigs weighing 9 to 16 kg. A 5.5- or 7.5-Fr Swan
      Ganz catheter was introduced into the femoral or jugular vein, and a 4- or 5-Fr
      arterial PiCCO catheter was introduced into the femoral artery. In each animal,
      we made measurements of cardiac output at 30-minute intervals, simultaneously by
      pulmonary arterial thermodilution and femoral arterial thermodilution, before,
      during, and after hemodiafiltration carried out via different venous catheters,
      recording a total of 78 measurements. The mean Swan-Ganz cardiac output was 2.22
      +/- 0.94 L/min, and mean PiCCO cardiac output was 1.94 +/- 0.80 L/min (no
      significant difference). The mean difference (bias) of differences (limits of
      agreement) was 0.2812. The differences between the methods increased with higher
      cardiac output, but the percentage differences in relation to cardiac output
      remained stable. Good correlation was found between the two methods: single
      measure intraclass correlation was 0.8892 (95% confidence interval, 0.54-0.95).
      There were no differences between the 5.5- and 7.5-FR Swan-Ganz catheters or
      between the 4- and 5-Fr PiCCO catheters. Femoral arterial thermodilution cardiac
      output measurements correlated well with pulmonary arterial thermodilution
      cardiac output measurements in a pediatric animal model.

PMID- 14681743
TI  - [Two simulation programs to measure continuous attention in obstructive sleep
      apnea syndrome].
AB  - Patients with obstructive sleep apnea syndrome suffer from reduced continuous
      attention due to neuropsychological deficits. Among other means, driving
      simulator programs are employed for registration and objectification as well as
      observation of the course of therapy. While Steer Clear by Findley et al. and the
      driving simulator Carda (Randerath et al.) represent pure continuous attention
      tests, the new driving simulator test Carsim, measures attention interactively
      and continuously. This way, more complex functions are recorded. We therefore
      investigated Carda and the program Carsim to study the various features of both
      methods. For this purpose, 105 OSAS patients were tested on both driving
      simulators concerning the mistake rate in Carda and the time of tracking
      deviations in Carsim. We defined the normal range by using the mean value +/- 2
      standard deviations from our earlier publications in healthy persons without
      sleep disorders. With Carda the mistake rate exceeded in 10 of 105 patients
      (9.5%) the normal range and with Carsim the frequency of tracking deviations
      exceeded in 49 of 105 patients (46.7%) the normal range. The incidence of
      deviation from normal was significantly higher with Carsim testing. By
      additionally testing the number of pathological cases is with Carda increased
      from 46.7% to 51.4%. The tests characterize different components of
      neuropsychological deficits. Driving simulators with tracking tasks describe
      neuropsychological deficits in comparison with those measuring only components of
      reaction in a higher percentage.

PMID- 14681744
TI  - [Sleep-disordered breathing in neuromuscular diseases].
AB  - Sleep-disordered breathing is common in neuromuscular diseases but remains poorly
      defined in its relationship to daytime respiratory function. METHODS: We
      prospectively compared supine lung and respiratory muscle function with results
      of polysomnography/capnometry in 35 patients with progressive myopathies (age
      32.5 +/- 15 years). RESULTS: 32/35 patients had restrictive ventilatory defect,
      9/32 had hypercapnic respiratory failure by day (PaCO(2) 66.0 +/- 15.7 mm Hg).
      Supine inspiratory vital capacity (IVC(S)) correlated with maximal inspiratory
      muscle pressure (R = 0.75), respiratory muscle strain (P0.1/PImax, R = - 0.68),
      and daytime blood gases (p < 0.005 for all). SDB in the way of REM-sleep
      hypopneas, circumscribed hypoventilation episodes and sleep-stage independent
      continuous hypoventilation (PtcCO(2) > 50 mmHg > 50% of sleep time) was common at
      IVC(S)< 60% pred, and preceded daytime hypercapnia. IVC(S) correlated with
      nocturnal SaO(2) (R = 0.64), PtcCO(2) (R = - 0.87), percent light sleep (R =
      0.67) and deep sleep (R = - 0.76). IVC(S) correlated only marginally with
      respiratory disturbance index (total sleep, R = - 0.45; REM-sleep, R = - 0.44).
      IVC(S) < 60% was 96% sensitive, 78% specific for presence of SDB. IVC(S) < 20 %
      was 89% sensitive, 96% specific for daytime hypercapnia. CONCLUSIONS: IVC(S)
      correlates with respiratory muscle function, daytime and nocturnal blood gases,
      and is highly predictive of SDB and daytime hypercapnia.

PMID- 14681746
TI  - [Validation of microMESAM as screening device for sleep disordered breathing].
AB  - INTRODUCTION: Polysomnography (PSG) is considered the gold standard in the
      diagnosis of sleep disordered breathing (SDB). Because of costs and labor
      intensity it is, however, performed last in graded diagnostic protocols that
      often involve respiratory pressure measurements via nasal canula as an
      alternative sensitive method for SDB detection. MicroMESAM, a newly developed
      screening device based on this method, allows automated analysis of apnoeas,
      hypopnoeas and snoring. AIM AND METHODS: To validate the device, we first
      compared signal quality of MicroMESAM flow-time curves with those generated by a
      pneumotachograph. Then, in 50 patients suspected of having obstructive sleep
      apnoea, we compared MicroMESAM-generated automated analysis with manually scored
      results of simultaneously collected PSG data. RESULTS: MicroMESAM-generated flow
      time curves correspond with pneumotachograph-generated curves in 95% of
      respiratory events, resulting in less 4 +/- 2% difference in respective area
      under the curves. MicroMESAM and PSG generated numbers of apnoeas (r = 0.99) and
      hypopnoea (r = 0.81), as well as AHI (r = 0.98) correlated highly, displaying
      mean differences in AHI of 3.8, and in 1.96 sigma interval of + 11.1 to - 3.5/h.
      Sensitivities and specificities for SDB were 97.3%, respective 46% at SDB
      defining AHI of 5, and 100%, respective 87.5%, at SDB-defining AHI of 10.
      SUMMARY: MicroMESAM-generated flow-time curves correspond well with
      pneumotachograph generated curves, producing automated AHIs that are highly
      sensitive in detecting SDB. MicroMESAM, therefore, is suitable as a screening
      device for SDB.

PMID- 14681747
TI  - [Benign fibrous histiocytomas as a differential diagnosis in cavitary lung
      disease].
AB  - Benign fibrous histiocytomas (BFH) are uncommon pulmonary tumours. These lesions
      usually present as slow-growing, solid masses. We report the rare case of a young
      man with cavitary BFH. The 20-year-old patient, a non-invasive drug abuser, had
      suffered from hemoptysis for two months. The chest X-ray showed a solitary
      pulmonary nodule with a diameter of 2 cm in the left lower lobe with central
      cavitation. Fiberoptic bronchoscopy showed a normal bronchial system, biopsies
      were not diagnostic and no acid fast bacilli were found. Considering the
      patient's history and the cavitary process, a non-specific abscess was suspected
      and an antimicrobial treatment was started. Since no treatment effect was
      observed, biopsies from a second bronchoscopy were suspicious of a malignant
      mesenchymal tumour. Lower lobe resection with lymphadenectomy revealed a benign
      fibrous histiocytoma. This is--to our knowledge--the first reported case of a BFH
      presenting with cavitation.

PMID- 14681748
TI  - [One year of asthma treatment: a retrospective analysis of 57 patients in the
      year 1997].
AB  - A persisting stabilisation without symptoms or exacerbations is the aim of modern
      asthma treatment. The costs on this basis are lower than we expected. METHODS: We
      collected data from all asthma patients who were treated for asthma in our
      practice in all 4 quarters of 1997 regarding treatment and prescriptions.
      RESULTS: Data from 57 asthma patients (34 women, 23 men), 39 with low degree
      asthma, 16 with medium degree and 2 with severe asthma, were analysed. The
      duration of treatment ranged from 5 to 13 years. The frequency of contacts with
      the practice and lung function tests changed according to the degree of severity
      with an average of 9.3 respectively 2.1. Emergency or hospital treatment did not
      become necessary. Apart from one female patient all others received inhalative
      glucocorticoids. The use of beta 2 agonists varied. The main costs of treatment
      and prescription was 524.30 euros, rising with the degree of severity.
      CONCLUSIONS: A successful and affordable treatment of asthma is possible.
      Combined with clinical examinations, peak-flow measurements and lung function
      tests the prescriptions can help in the staging of severity of asthma. Emergency
      treatment can thus be avoided.

PMID- 14681749
TI  - [Cardiac sarcoidosis].
AB  - Sarcoidosis is a systemic disease, in which early inflammatory organic changes,
      which are often reversible under treatment, may take a subclinical course. In
      scarred residual tissue improvement id rare. Continuing functional loss or even
      organ failure is possible. The involvement of the heart is of essential
      prognostic value. Early onset of treatment with corticosteroids before
      irreversible functional loss of the heart occurs leads to an excellent prognosis.
      Technical progress in the imaging techniques have led to great improvement of the
      graphical presentation of cardiac structure and function, but not one of these
      techniques has yet been approved of for early diagnosis. Still, a combination of
      different diagnostical measures in addition to the evaluation of clinical
      symptoms often allows early diagnosis. A decisive factor is "to consider it" and
      a timely start of further diagnostics if certain symptoms are presented.
      Alternatives to the specific treatment with cortisone are still lacking.
      Symptomatic cardiac treatment is mainly oriented on the therapy of dilatory
      cardiomyopathies, since there are no reliable systematic studies available on
      questions concerning, for example, antiarrhythmic treatment or indications for
      the implantations of pacemakers in connection with cardiac sarcoidosis.

PMID- 14681750
TI  - [Strictly controlled chemotherapy of tuberculosis--executed for the first time on
      a larger scale in Germany 30 years ago].

PMID- 14681751
TI  - [Nikolaus Konietzko on the occasion of his 65th birthday].

PMID- 14681752
TI  - The development of cerebral perfusion in healthy preterm and term neonates.
AB  - Quantitative measurement of cerebral blood flow (CBF) volume was performed by
      sonographic flowmetry of both internal carotid (ICA) and vertebral arteries (VA)
      in 113 healthy preterm and term infants of 32 - 42 weeks postmenstrual age (PA)
      in order to delineate the physiological characteristics of brain perfusion in a
      time period very sensitive to brain injury. Mean CBF volume increased with PA,
      beginning with 33 +/- 9 ml/min in neonates of 32 - 34 weeks and rising to 45 +/-
      10, 58 +/- 13, 69 +/- 14, and 83 +/- 16 ml/min, respectively, in the PA groups of
      35 - 36, 37 - 38, 39 - 40 and 41 - 42 weeks. There was no difference in CBF
      volume between the sexes. The bilateral sum of flow volumes in both ICA and VA
      rose markedly with PA. The relative contribution of bilateral VA flow volume to
      total CBF volume was 26 +/- 8 % and remained constant with PA. In addition, we
      calculated the approximate CBF (ml/100 g brain weight/min) using the brain
      weights of each child as estimated by means of an equation based on head
      circumference measurements. Estimated CBF correlated significantly with PA (r =
      0.49; p </= 0.0001), reflecting the rising metabolic demand of the growing brain
      during the time period examined.

PMID- 14681753
TI  - Characterization of brain malformations in the Baraitser-Winter syndrome and
      review of the literature.
AB  - Baraitser-Winter syndrome is a rare autosomal recessive disorder characterized by
      developmental delay, dysmorphic features, and multiple malformations also
      involving the brain. We report a further case and provide updated information
      about an unrelated girl reported in the original paper by Baraitser and Winter.
      Both of them presented with pachygyria and the latter case was recently found to
      have subcortical band heterotopia on high resolution brain MRI imaging. These two
      patients and a review of the previously reported cases indicate that a specific
      pattern of brain anomalies falling in the agyria-pachygyria-band spectrum is
      associated with this dysmorphic syndrome, which may be considered another example
      of syndromic neuronal migration defect.

PMID- 14681754
TI  - Sagittal craniosynostosis: cognitive development, behaviour, and quality of life
      in unoperated children.
AB  - 30 patients (23 m/7 f) with untreated, isolated sagittal craniosynostosis (ISC)
      were re-evaluated at an average age of 9.25 years (2.5 - 25.5). Assessed were
      neurological status, head shape, school performance, behaviour (with Child
      Behavior Checklist CBCL), quality of life (TACQOL questionnaire), and a detailed
      neuropsychological testing (30 patients, 17 siblings as controls). Almost all
      patients/parents were pleased with the current situation. The aesthetic
      appearance seemed less obvious compared to photos in infancy. Psychological
      adjustment as measured by the CBCL was well within normal range. There was a
      slight tendency for increased internalizing symptoms. TACQOL revealed a lower
      score for positive emotions. Total score and subscores of test batteries
      assessing general intellectual performance were in the average range. 6 patients
      had below average scores in subtests for learning and memory. 12 children had
      below average scores in one or more subtests for attention. These "deficits" were
      obviously not of functional importance as all children attended regular school
      classes (1 exception, an immigrant child of low socio-economic status). These
      reassuring results regarding school performances, behaviour, and quality of life
      as well as aesthetic outcome may be helpful when discussing the indication for
      surgical correction of ISC.

PMID- 14681755
TI  - Niemann-Pick disease type A and B are clinically but also enzymatically
      heterogeneous: pitfall in the laboratory diagnosis of sphingomyelinase deficiency
      associated with the mutation Q292 K.
AB  - This study describes a diagnostic pitfall in the laboratory diagnosis of patients
      with sphingomyelinase deficiency (SMD; Niemann-Pick disease types A and B; NPA
      and NPB), in cases where sphingomyelinase activity was not determined with
      sphingomyelin as the natural enzymic substrate. Four of 24 SMD patients studied
      had falsely normal or enhanced activity, when a so-called artificial
      sphingomyelinase substrate, 2-N-(hexadecanoyl)-amino-4-nitrophenyl
      phosphorylcholine (HNP), was used, whereas SMD was clear with the sphingomyelin
      substrate. Those four patients had the Q292 K mutation of the acid
      sphingomyelinase gene (SMPD1) on at least one allele. Three of the four patients
      (no data available from one) experienced only late-infantile or juvenile, though
      distinct, neurological involvement, where learning disabilities, hypo- or
      areflexia or mild ataxia were initial signs. The laboratory pitfall with HNP
      substrate, which is used in many laboratories, raises the risk that some SMD
      patients are overlooked, and it prevents the consideration of a late-manifesting
      neurological course in some patients as well as the planning of enzyme
      substitution therapy in non-neurological SMD (NPB) patients. Since classical NPB
      is very rare, it is suggested that SMD patients with late- or mild-manifesting
      neurological symptoms should better be assigned to additional SMD subgroups than
      grouped with NPB.

PMID- 14681756
TI  - Vertebral artery dissection in an infant: ultrastructural aberrations in
      connective tissue components.
AB  - We report on a 14-month-old boy who had acute multiple infarcts in the posterior
      circulation due to an extremely early onset of spontaneous vertebral artery
      dissection. Despite the absence of clinical signs of connective tissue disorders,
      an ultrastructural change of collagen fibrils and elastic fibers indicated
      connective tissue abnormalities. Arterial dissection should be considered as a
      cause of stroke during infancy.

PMID- 14681757
TI  - Genotypes and clinical phenotypes in children with cytochrome-c oxidase
      deficiency.
AB  - Cytochrome c oxidase (COX) deficiency has been associated with a wide spectrum of
      clinical features and may be caused by mutations in different genes of both the
      mitochondrial and the nuclear DNA. In an attempt to correlate the clinical
      phenotype with the genotype in 16 childhood cases, mtDNA was analysed for
      deletion, depletion, and mutations in the three genes encoding COX subunits and
      the 22 tRNA genes. Furthermore, nuclear DNA was analysed for mutations in the
      SURF1, SCO2, COX10, and COX17 genes and cases with mtDNA depletion were analysed
      for mutations in the TK2 gene. SURF1-mutations were identified in three out of
      four cases with Leigh syndrome while a mutation in the mitochondrial tRNA (trp)
      gene was identified in the fourth. One case with mtDNA depletion had mutations in
      the TK2 gene. In two cases with leukoencephalopathy, one case with
      encephalopathy, five cases with fatal infantile myopathy and cardiomyopathy, two
      cases with benign infantile myopathy, and one case with mtDNA depletion, no
      mutations were identified. We conclude that COX deficiency in childhood should be
      suspected in a wide range of clinical settings and although an increasing number
      of genetic defects have been identified, the underlying mutations remain unclear
      in the majority of the cases.

PMID- 14681758
TI  - Moyamoya and extracranial vascular involvement: fibromuscular dysplasia? A report
      of two children.
AB  - We present two patients with moyamoya syndrome and the unusual involvement of
      extracranial vessels. The first case illustrates the rare association between
      moyamoya and primary pulmonary hypertension. In the second patient, moyamoya was
      complicated by stenoses of vertebral, renal, and mesenteric arteries. In both
      cases, a systemic intima-proliferative disease, such as fibromuscular dysplasia
      (FMD), was suspected to be the cause of both intracranial and extracranial
      arterial disease.

PMID- 14681759
TI  - Frameshift mutation of the zinc finger homeo box 1 B gene in syndromic corpus
      callosum agenesis (Mowat-Wilson syndrome).
AB  - We report a girl who had Hirschsprung disease in association with distinct facial
      appearance, microcephaly, agenesis of the corpus callosum and mental retardation
      (Mowat-Wilson syndrome). Mutation analysis of the zinc finger homeo box 1 B
      (ZFHX1 B) gene revealed a de novo 7 bp deletion (TGGCCCC) at nucleotide 1773
      (1773 delTGGCCCC) resulting in a frameshift and leading to a termination codon at
      amino acid residue 604 (604 X) in exon 8 C. The zinc finger homeo box 1 B (Smad
      interacting protein-1) is a transcription corepressor of Smad target genes with
      functions in the patterning of neural crest derived cells, CNS, and midline
      structures. Mutations in ZFHX1 B can lead to neurological disorders in addition
      to dysmorphic features, megacolon, and other malformations.

PMID- 14681760
TI  - Subacute sclerosing panencephalitis in two brothers.
AB  - We report the occurrence of subacute sclerosing panencephalitis (SSPE) in two
      brothers two years after measles infection. The diagnosis was confirmed by
      compatible data from medical history, occurrence of autochthonic measles virus
      (MV) IgG production in the central nervous system (CNS), and pathognomonic EEG
      changes. Pathogenetically, SSPE is caused by a genome mutation of intracellularly
      persisting MV, causing viral nucleocapsides to accumulate in the brain cells. A
      specific predisposing immune defect is not known. The occurrence of two cases in
      one family is suggestive of a genetic predisposing factor.

PMID- 14681761
TI  - Intracerebral inflammatory pseudotumour in a 16-month-old boy.
AB  - A 16-month-old boy presenting with a previous two-month history of absences, was
      admitted for partial seizures and vomiting. Magnetic resonance imaging revealed a
      left temporo-occipital intraparenchymatous, well circumscribed lesion. Complete
      macroscopic resection was performed. Morphological and immunohistochemical
      analyses were conclusive for an inflammatory pseudotumour. Only a few cases of
      intracranial locations of this entity have been reported. Our case is the first
      described in an infant younger than four years of age. This observation suggests
      that chronic evolution may start earlier than thought in adult cases, perhaps due
      to an autoimmune process.

PMID- 14681762
TI  - HHV-6 in CSF samples.

PMID- 14681763
TI  - Muscle ultrasound in Bethlem myopathy.

PMID- 14681764
TI  - [The treatment of flexor tendon injuries in children].
AB  - Full functional recovery must always be the aim of flexor tendon reconstruction.
      This not only applies to adults, but particularly to infants. As customary, also
      in a child a severed flexor tendon should be attended immediately or with only a
      short delay. However, we definitively reject a bandaged fist of a hand and rather
      recommend demobilization by a modified Kleinert plaster. At the University Clinic
      for Paediatric Surgery in Graz over ten years ago we established a therapeutic
      protocol dedicated to infants, which we evaluated recently. In this study
      questions addressed were whether this treatment regimen is applicable for all age
      groups, notably whether the dynamic post operative treatment with a modified
      Kleinert plaster is always advisable. A total of 211 severed flexor tendons in
      children from nine months to 18 years (median 7 years) were treated. 193 lesions
      were either reconstructed immediately or within 48 hours. As a rule we apply the
      Kirchmayr-Zechner suturing procedure. We believe that the desired full mobility
      can thus be obtained within three months. In 95% of the 173 cases followed-up we
      achieved this goal with good or even excellent results according to Buck
      Gramcko's criteria.

PMID- 14681765
TI  - [Treatment of flexor tendon injuries in children].
AB  - In contrast to the standard therapy of flexor tendon injuries in adults, the
      postoperative treatment program for children remains a controversial topic. Some
      prefer immobilization therapy in a variety of forms and for different periods of
      time. Others prefer early mobilization programs. We present results for twenty
      eight children with thirty-seven flexor tendon injuries. The average age was 5.8
      years. After primary tendon suture in children six years and younger (group A),
      our postoperative program consisted of immobilization for three weeks. The older
      children (group B) were treated with an early passive mobilization program.
      Follow-up examinations were carried out on twenty six of the children at three
      months and at 3.7 years. Three months after surgery, the children in group A
      showed only average results while those in group B presented good finger motion.
      After 3.7 years both groups showed good results.

PMID- 14681766
TI  - [Results after staged reconstruction of the flexor pollicis longus tendon].
AB  - The objective of this study was to evaluate results after staged reconstruction
      of the flexor pollicis longus tendon (FPL) and to compare the results with
      literature. The advantages and disadvantages of staged reconstruction with a
      total duration of therapy of four months are discussed and theoretically compared
      with the simple and fast alternative, the arthrodesis of the interphalangeal
      joint (IP) of the thumb. The results of 22 patients from 1993 until 2000, 16 of
      which could be re-examined, are presented. Clinical parameters (grip strength and
      motion) were evaluated as well as the DASH score. In all cases a long graft to
      the forearm was used. The second operation usually followed eight weeks after the
      first operation. The results show a sufficient function in 75 % of the cases
      (scoring system of Buck-Gramcko et al.), which is paralleled by a median of 11 in
      the DASH score. The study shows that staged reconstruction can produce
      satisfactory results even in thumbs. The results are influenced negatively by
      persistent flexion contractures, insufficiency of annular pulleys and ailments
      after algodystrophy, which can be seen as indicator of the severity of the
      initial injury.

PMID- 14681768
TI  - [Reconstruction of the extensor pollicis longus tendon by transposition of the
      extensor indicis tendon].
AB  - Rupture of the extensor pollicis longus-tendon (EPL) is a frequent complication
      after distal radius fractures. Other traumatic and non-traumatic reasons for this
      tendon lesion are known, including a theory about a disorder in the blood supply
      to the tendon itself. We examined 40 patients after reconstruction of the EPL
      tendon in a mean follow-up time of 30 months. All patients were clinically
      examined and a DASH questionnaire was answered by all patients. The method to
      reconstruct the EPL-tendon was the transposition of the extensor indicis-tendon.
      After the operations the thumb was put in a splint for four weeks in a "hitch
      hiker's-position". 31 ruptures of the tendon (77.5 %) were a result of trauma. In
      20 of them (50 %) a distal radius fracture had occurred. Clinical examination
      included measurements of the movement of the thumb- and index-finger joints, the
      grip strength and the maximal span of the hand. Significant differences were not
      found. The isolated extension of the index finger was possible in all patients.
      But it was reduced in ten cases which represent 25 %. Our results were evaluated
      by the Geldmacher score to evaluate the reconstruction of the EPL-tendon. 20 %
      excellent, 65 % good, 12.5 % fair and 2.5 % poor results were reached. The
      Geldmacher score was used critically. We suggest its modification for the
      evaluation of thumb abduction. The DASH score reached a functional value of ten
      points which represents a very good result. In conclusion the extensor indicis
      transposition is a safe method to reconstruct the EPL-tendon. Its substantial
      advantage is taking a healthy muscle as the motor, thereby avoiding the risk of
      using a degenerated muscle in late tendon reconstruction. A powerful extension of
      the index finger will be maintained by physical education. Generally, the loss of
      the extension of the index finger is negligible. It does not disturb the
      patients. But it has to be discussed with the patient before the operation.

PMID- 14681767
TI  - [The Mantero technique for flexor tendon repair - an alternative?].
AB  - PURPOSE: Regaining free tendon gliding after reconstruction of flexor tendons is
      essential to restore full function to the affected finger. Mantero et al.
      described a pull-out suture technique for the repair of flexor digitorum
      profundus (FDP) lesions in zone 1, allowing early postoperative active
      mobilisation and thus minimizing the risk of tendon adhesions. In a retrospective
      study we examined the results after Mantero tendon repair and compared these with
      the results after different reconstructive procedures in the literature. METHODS
      AND MATERIAL: Between 1995 and 2001, the FDP tendon in zone 1 and distal half of
      zone 2 distal to the chiasma respectively the flexor pollicis longus (FPL) tendon
      were reconstructed in 96 patients using the Mantero technique. 87 (90 %)
      patients, with a male to female ratio of 2 : 1, were re-examined an average of 43
      (4 to 84) months postoperatively. We evaluated the isolated function of the
      finger joints, the total range of motion of the affected finger and grip strength
      and compared all values to the contralateral healthy side and assessed the
      functional results according to the Buck-Gramcko score and the patients'
      satisfaction according to the DASH score. Special attention was directed to the
      influence of the patients' age, gender, art of trauma, accompanying injuries or
      level of the lesion on the postoperative results. Furthermore, we evaluated
      whether clinical results depended on which finger was injured. RESULTS: 71 % (n =
      62) of all injuries were found in the distal zone 2 or distal zone Th 2 in the
      thumb. While 81 % (n = 70) were caused by a clean cut, 10 % (n = 9) were due to a
      circular saw injury and 9 % (n = 8) due to a crush injury. The average DASH score
      value was 5.4 (0 to 37.5) with excellent and good results according to the Buck
      Gramcko score in 90.8 % (n = 79) of all patients. Only the patients' age (> 50
      years vs. < 20 years) and the digit involved (little finger vs. index, middle and
      ring fingers) had a significant influence on the postoperative results. Aside
      from superficial skin necrosis in 10 % of all cases, in which no further
      operative therapy was necessary, no other complications occurred. Interestingly,
      no ruptures of the sutured tendons were found, although active mobilisation was
      initiated immediately. Compared to the literature, the 90,8 % excellent and good
      results are equivalent to those of other studies concerning reconstruction after
      flexor tendon injuries using the Mantero technique and tend to be better than
      other reconstructive procedures. CONCLUSION: Based on our results, we consider
      the Mantero technique to be a good alternative to other forms of flexor tendon
      reconstruction in zone 1 and distal zone 2. Advantages include the possibility of
      immediate postoperative mobilisation and placing a secure tendon suture, even if
      the distal tendon stump is very short.

PMID- 14681769
TI  - [Secondary reconstruction of extensor pollicis longus tendon].
AB  - BACKGROUND: Secondary reconstruction of the extensor pollicis longus tendon (EPL)
      can be performed using an intercalated tendon graft (ITG) or a tendon
      transposition, preferably the extensor indicis transposition (EIT), since a
      secondary suture of the EPL tendon is not possible in most cases due to
      degenerative changes or defect injuries. A direct comparison of ITG and EIT in
      one single patient collective based on a standardized follow-up protocol has not
      been performed yet. PATIENTS AND METHOD: For the first time, these two operative
      procedures were directly compared in a retrospective analysis according to the
      follow-up protocol after Geldmacher et al. an average of 4.3 (2 to 11) years
      after reconstructive surgery. Out of 1469 extensor tendon lesions only 55
      patients were identified in the course of secondary reconstruction of the EPL
      tendon in whom additional injuries, especially osseous lesions or other
      conditions that affected the mobility of the thumb, could be ruled out reliably.
      45 (82 %) of these patients participated in a clinical follow-up examination. In
      28 (62 %) patients an EIT and in 17 (38 %) an ITG was performed. RESULTS: Neither
      the range of motion in the metacarpophalangeal and interphalangeal joint of the
      thumb, the abduction and the adduction of the thumb as well as the extension
      deficit and the remaining pulp-to-pulp distance during thumb opposition, compared
      to the contralateral hand, nor the overall evaluation showed a significant
      difference (Students-t-test; p < 0.05) between the results of both procedures.
      CONCLUSION: The EIT and the ITG for the secondary reconstruction of the EPL
      tendon should be regarded as equal alternatives.

PMID- 14681770
TI  - [Reconstruction of the ruptured extensor pollicis longus tendon using a tendon
      interposition graft].
AB  - To restore function of the ruptured extensor pollicis longus (EPL) tendon, two
      operative principles have been described: reconstruction of the original tendon
      using a tendon interposition graft or a tendon transposition operation, most
      commonly transposition of the extensor indicis. From 1992 to 1998, we
      reconstructed the extensor pollicis longus tendon using an interposition graft in
      58 patients. 48 patients were available for follow-up after a mean of 31 months.
      The mean age of the 25 women and 23 men was 49 years. The time between tendon
      rupture and reconstruction ranged from one to 40 weeks. The tendon rupture
      occurred in 19 patients following a radius fracture, in 22 patients without
      history of trauma and in seven patients it was due to a sharp injury. Using the
      clinical score of Geldmacher and Kockerling, five patients achieved a very good,
      35 patients a good and eight patients a satisfactory result. No patient had a
      poor result. According to the statistical analyses, these results were
      independent of the age of the patients, the origin of the rupture or the time
      interval between rupture and tendon reconstruction. The average DASH score
      measured 14. Considering our results, secondary reconstruction of the original
      EPL tendon appears to be a valuable alternative to the commonly performed tendon
      transpositions. It yields good clinical results with little remaining functional
      impairment and without the need to sacrifice another functional motor. We
      strongly recommend this technique in patients who require an independent and
      strong extension of the index finger in their profession (surgeons, musicians)
      and in patients with severe trauma that does not allow the sacrifice of another
      intact motor unit.

PMID- 14681771
TI  - [Operative procedure for repair of the dorsal aponeurosis promoting early active
      motion].
AB  - PURPOSE: To describe our method of treatment for extensor tendon laceration at
      the level of the distal and proximal interphangeal joint with early active motion
      following a special tendon suture and to evaluate the outcome. METHODS: In a
      retrospective study the results of 35 patients with 35 extensor tendon
      lacerations in zone 1 and 2, in whom the postoperative treatment consisted of
      immobilisation, were compared with the results of 24 patients, in whom 24
      extensor tendon lacerations in zone 1 and 2 were treated with early active motion
      following operative treatment. In addition, the outcome following immobilisation
      after operative treatment of 54 patients with 57 extensor tendon lacerations in
      zone 3 was compared to the outcome of 61 patients, who had undergone early active
      motion following operative treatment, with 65 extensor tendon lacerations in zone
      3. In patients, treated with early active motion, a special type of tendon suture
      was carried out. The outcome was ranked according to a scoring system developed
      by us. RESULTS: In extensor tendon laceration in zone 1 and 2 following active
      early motion there were 62.5 % excellent, 20.8 % good, 12.5 % satisfactory, and
      4.2 % unsatisfactory results. In patients with extensor tendon lacerations in
      zone 1 and 2, in whom the postoperative treatment consisted of immobilisation,
      45.7 % excellent, 22.9 % good, 20 % satisfactory, and 11.4 % unsatisfactory
      results were found. Following early active motion in patients with zone 3
      extensor tendon laceration, there were 70.8 % excellent, 15.4 % good, 9.2 %
      satisfactory, and 4.6 % unsatisfactory results. After postoperative
      immobilisation 59.7 % excellent, 14 % good, 12.3 % satisfactory, and 14 %
      unsatisfactory results were found. For extensor tendon laceration in zone 1 and
      2, there was a tendency to much better results in the early active motion group.
      However, the differences in the outcome of the two treatment groups were not
      statistically significant. There were significantly more good and excellent
      results and less unsatisfactory results in zone 3 extensor tendon lacerations
      following early active motion than following immobilisation. CONCLUSION: This
      data suggests that patients benefit by early active motion rehabilitation
      protocol following operative treatment for extensor tendon lacerations in zone 1
      to 3. Our special tendon suture proved in the practice well.

PMID- 14681772
TI  - [Infections of flexor tendon sheath - treatment and results].
AB  - Infections of the flexor tendon sheath are rare. We report on 49 patients who
      were treated in a five-year period from 1996 to 2000. The follow-up period was 45
      months on average. We used an extensive skin incision for revision and regularly
      placed gentamycin-PMMA-chains in the wound. All patients were treated as
      inpatients. We achieved good and excellent results in 85% of patients.

PMID- 14681773
TI  - [Downgrading of German DRG by additional operating procedures].
AB  - An error of German system of DRG grouping is represented and discussed which
      mainly concerns hand surgery.

PMID- 14681774
TI  - [Reply to the invited commentary of R. G. H. Baumeister to the article of G.
      Eder: Endoscopic carpal tunnel release without iatrogenic complication - a report
      about 1000 procedures].

PMID- 14681775
TI  - [Report on the travelling grant of the DAM 2001 - microsurgical research
      fellowship at the Cleveland Clinic Foundation].

PMID- 14681776
TI  - [Geese, carp, honey cakes, stollen. History, medicine and magic around the
      Christmas feast].

PMID- 14681777
TI  - [Religion and medicine: partners or opposites?].

PMID- 14681778
TI  - ["Transforming poetry into reality"--figures in the legends of antiquity in
      modern medicine].

PMID- 14681779
TI  - [From the heart to the brain].

PMID- 14681780
TI  - [Music as adjuvant therapy for coronary heart disease. Therapeutic music lowers
      anxiety, stress and beta-endorphin concentrations in patients from a coronary
      sport group].
AB  - BACKGROUND: In a study with coronary patients it was estimated that music is able
      to lower stress and fear and contributing to relaxation in spite of physical
      exercise. PATIENTS AND METHODS: 15 patients (13 male, two female, mean age 62,2
      +/- 7,6 years) of a coronary sport unit were listening to an especially composed
      relaxation music while training their common heart-frequency adapted exercises.
      Before the exercises and after listening to music blood pressures were measured
      and blood was collected for determination of beta-endorphin. Simultaneous to
      blood collection the participants had to perform two psychometric test: the
      perceived stress experience questionnaire (PSQ) of Levenstein to measure the
      graduation of subjective perceived stress and the state-anxiety inquiry (STAI) of
      Spielberger as an indicator of coping. To practice the trial ("test trial"), the
      whole protocol was performed one week prior to the mean trial, but without
      listening to music and without blood collections and blood pressure measurements.
      RESULTS: In the test trial without music there were no significant changes in PSQ
      data. In the mean trial, under the influence of music, values in the section
      "worries" decreased as a sign of lower worries (26.6 versus 27.6; p = 0.039).
      STAI-values were significantly lower as a sign of reduced fear after listening to
      music (31 versus 34; p = 0.045). beta-endorphin concentration (10.91 microg/l
      versus 15.96 microg/l, p = 0.044) and systolic blood pressure (130 mmHg versus
      140 mmHg; p = 0.007) decreased significantly after listening to music.
      CONCLUSIONS: Regarding worries and fear, patients seemed to benefit by the
      intervention of music. beta-endorphin was lowered significantly after music
      despite physical activity.

PMID- 14681781
TI  - [Typically German? Awareness of German publications within Germany itself].

PMID- 14681782
TI  - [Human medical experimentation as a literary topic].

PMID- 14681816
TI  - Brain reorganization after stroke.
AB  - After a stroke, recovery that continues beyond 3 or 4 weeks has been attributed
      to plasticity, a reorganization of the brain in which functions previously
      performed by the ischemic area are assumed by other ipsilateral or contralateral
      brain areas. Neuronal plasticity has been variously attributed to redundancy
      (parallel distributed pathways), changes in synaptic strength, axonal sprouting
      with formation of new synapses, assumption of function by contralateral
      homologous cortex, and substitution of uncrossed pathways. Transcranial magnetic
      stimulation, positron emission tomography (PET), functional magnetic resonance
      imaging (fMRI), and 128-electrode high-resolution electroencephalography have
      been successfully applied to demonstrate cortical reorganization after
      hemiplegia. Recording the motor potential is a promising noninvasive method for
      the localization of motor control after hemispheric lesions. Most patients with
      hemiparetic stroke show some improvement, usually during the first 3 to 6 months
      after the ictus. Improvement and prognosis depend on a number of variables
      including volume and location of the infarction, age of the patient, and the
      elimination of risk factors to avoid future episodes (i.e., dietary control of
      lipids, the elimination of tobacco, and the control of diabetes and
      hypertension). Currently, emphasis has been placed on fibrinolytic treatment in
      the first 3 hours to prevent or minimize neurological deficit. Aside from the
      above listed factors, improvement after stroke may be due to reorganization of
      the brain, particularly the cerebral cortex, and repair of damaged tissue and
      recanalization. It is also important to relate such changes to functional
      improvement and successful rehabilitation.

PMID- 14681817
TI  - Thrombophilia and stroke.
AB  - Thrombophilia is defined as an enhanced tendency to form intravascular thrombi,
      which may be arterial or venous. Of the inherited thrombophilias, factor V Leiden
      and the prothrombin 20210 mutation have been associated with stroke, but this
      association is statistically significant only in children and adults under age
      40. The risk of stroke in persons with these mutations is substantially increased
      by concomitant exposure to oral contraceptives. Hyperhomocystinemia is a major
      risk factor for stroke as well as Alzheimer's disease; persons with deficiencies
      of vitamin B12 or folic acid are especially vulnerable to these complications. Of
      the acquired thrombophilias, the antiphospholipid antibody syndrome is strongly
      associated with transient ischemic attacks, cerebral infarction, Sneddon
      syndrome, and dementia. The diagnosis of thrombophilia should be considered in
      stroke patients who are young, have a family history of thrombosis, suffer venous
      dural sinus thrombosis, or have recurrent strokes.

PMID- 14681818
TI  - Medical management of patients with an acute stroke: treatment and prevention.
AB  - Stroke is a common and serious disorder and will probably occur with increasing
      frequency due to an aging of the population. Acute therapies aimed at reversing
      the effects of acute ischemic stroke are limited to recombinant tissue
      plasminogen activator administered intravenously within 3 hours of stroke onset.
      Neuroprotective agents and acute anticoagulation with agents such as heparinoids
      and heparin are not effective in most cases. Poststroke medical complications
      such as infection and venous thromboembolism are common but are largely
      preventable. A variety of medical therapies such as antiplatelet agents,
      warfarin, statins, and ACE inhibitors can reduce the risk of a recurrent stroke.
      A key aspect of management for stroke is selection of the proper treatment
      regimen for each patient.

PMID- 14681819
TI  - Carotid artery revascularization.
AB  - Stroke is the third leading cause of death in the United States, and up to one
      third of patients have a stroke secondary to carotid occlusive disease. Surgical
      management has firmly established itself as an important modality in treating
      this disease. Several prospective randomized trials have defined the patients
      that would have the most benefit from carotid endarterectomy (CEA). These patient
      populations include asymptomatic patients with a >or= 60% stenosis and
      symptomatic patients with a >or= 50% stenosis. The timing of CEA after stroke
      remains controversial, but recent studies advocate early CEA in a select group of
      patients. During the CEA, the method of closing of the arteriotomy has an overall
      effect on the safety of the procedure as well as long-term outcome. As compared
      with primary repair of the arteriotomy, patch closure has been shown to decrease
      the frequency of restenosis. In addition, carotid eversion endarterectomy (CEE)
      is an alternative method to remove the plaque that has a similar efficacy to
      standard CEA. The role of carotid angioplasty and stenting (CAS) continues to
      evolve and offers the patient a less invasive method of treating the carotid
      plaque.

PMID- 14681820
TI  - Prevention of venous thromboembolism after stroke.
AB  - Venous thromboembolism (VTE) is a common complication following acute ischemic
      and hemorrhagic stroke. Pulmonary embolism (PE), the most serious consequence of
      deep vein thrombosis (DVT), can result in significant morbidity and death.
      Patients with stroke are at particular risk because of limb paralysis, prolonged
      bed rest, and increased prothrombotic activity. Preventive measures should be
      taken at all levels of care and can include mechanical calf compression,
      antiplatelet agents, and the use of anticoagulants such as heparin and low
      molecular weight heparin. Prevention of VTE should be incorporated into all
      stroke care pathways.

PMID- 14681821
TI  - The suitability of written education materials for stroke survivors and their
      carers.
AB  - This study evaluated the suitability of written materials for stroke survivors
      and their carers. Twenty stroke survivors and 14 carers were interviewed about
      the stroke information they had received and their perceptions of the content and
      presentation of materials of increasing reading difficulty. The mean readability
      level of materials (grade 9) was higher than participants' mean reading ability
      (grade 7-8). Satisfaction with materials decreased as the content became more
      difficult to read. Seventy-five percent reported that their information needs
      were not met in hospital. More stroke survivors with aphasia wanted support from
      health professionals to read and understand written information, and identified
      simple language, large font size, color, and diagrams to complement the text as
      being important features of written materials. Simple materials that meet
      clients' information needs and design preferences may optimally inform them about
      stroke.

PMID- 14681822
TI  - Taping life back together: a low-tech experience in recovering reading ability.
AB  - The effectiveness of assistive technology may not be proportional to its
      complexity and sophistication. This article describes the experience of a stroke
      victim and his sister who work together to transform a simple tape recorder into
      a powerful springboard to regaining reading and comprehension capability.

PMID- 14681825
TI  - Mutation of CERKL, a novel human ceramide kinase gene, causes autosomal recessive
      retinitis pigmentosa (RP26).
AB  - Retinitis pigmentosa (RP), the main cause of adult blindness, is a genetically
      heterogeneous disorder characterized by progressive loss of photoreceptors
      through apoptosis. Up to now, 39 genes and loci have been implicated in
      nonsyndromic RP, yet the genetic bases of >50% of the cases, particularly of the
      recessive forms, remain unknown. Previous linkage analysis in a Spanish
      consanguineous family allowed us to define a novel autosomal recessive RP (arRP)
      locus, RP26, within an 11-cM interval (17.4 Mb) on 2q31.2-q32.3. In the present
      study, we further refine the RP26 locus down to 2.5 Mb, by microsatellite and
      single-nucleotide polymorphism (SNP) homozygosity mapping. After unsuccessful
      mutational analysis of the nine genes initially reported in this region, a
      detailed gene search based on expressed-sequence-tag data was undertaken. We
      finally identified a novel gene encoding a ceramide kinase (CERKL), which
      encompassed 13 exons. All of the patients from the RP26 family bear a homozygous
      mutation in exon 5, which generates a premature termination codon. The same
      mutation was also characterized in another, unrelated, Spanish pedigree with
      arRP. Human CERKL is expressed in the retina, among other adult and fetal
      tissues. A more detailed analysis by in situ hybridization on adult murine retina
      sections shows expression of Cerkl in the ganglion cell layer. Ceramide kinases
      convert the sphingolipid metabolite ceramide into ceramide-1-phosphate, both key
      mediators of cellular apoptosis and survival. Ceramide metabolism plays an
      essential role in the viability of neuronal cells, the membranes of which are
      particularly rich in sphingolipids. Therefore, CERKL deficiency could shift the
      relative levels of the signaling sphingolipid metabolites and increase
      sensitivity of photoreceptor and other retinal cells to apoptotic stimuli. This
      is the first genetic report suggesting a direct link between retinal
      neurodegeneration in RP and sphingolipid-mediated apoptosis.

PMID- 14681826
TI  - Selecting a maximally informative set of single-nucleotide polymorphisms for
      association analyses using linkage disequilibrium.
AB  - Common genetic polymorphisms may explain a portion of the heritable risk for
      common diseases. Within candidate genes, the number of common polymorphisms is
      finite, but direct assay of all existing common polymorphism is inefficient,
      because genotypes at many of these sites are strongly correlated. Thus, it is not
      necessary to assay all common variants if the patterns of allelic association
      between common variants can be described. We have developed an algorithm to
      select the maximally informative set of common single-nucleotide polymorphisms
      (tagSNPs) to assay in candidate-gene association studies, such that all known
      common polymorphisms either are directly assayed or exceed a threshold level of
      association with a tagSNP. The algorithm is based on the r(2) linkage
      disequilibrium (LD) statistic, because r(2) is directly related to statistical
      power to detect disease associations with unassayed sites. We show that, at a
      relatively stringent r(2) threshold (r2>0.8), the LD-selected tagSNPs resolve
      >80% of all haplotypes across a set of 100 candidate genes, regardless of
      recombination, and tag specific haplotypes and clades of related haplotypes in
      nonrecombinant regions. Thus, if the patterns of common variation are described
      for a candidate gene, analysis of the tagSNP set can comprehensively interrogate
      for main effects from common functional variation. We demonstrate that, although
      common variation tends to be shared between populations, tagSNPs should be
      selected separately for populations with different ancestries.

PMID- 14681827
TI  - Population-genetic basis of haplotype blocks in the 5q31 region.
AB  - We investigated patterns of nucleotide variation in the 5q31 region identified by
      Daly et al. as containing haplotype blocks, to determine whether the blocklike
      pattern requires the assumption of hotspots in recombination. Using extensive
      simulations that generate data matched to the Daly et al. data set in (a) the
      method of ascertainment of single-nucleotide polymorphisms, (b) the
      heterozygosity of ascertained markers, (c) the number of block boundaries, and
      (d) the diversity of haplotypes within blocks, we show that the patterns found in
      the Daly et al. data are not consistent with the assumption of uniform
      recombination in a population of constant size but are consistent either with the
      presence of hotspots in a population of constant size or with the absence of
      hotspots if there was a period of rapid population growth. We further show that
      estimates of local recombination rate can distinguish between population growth
      and hotspots as the primary cause of a blocklike pattern. Estimates of local
      recombination rates for the Daly et al. data do not indicate the presence of
      recombination hotspots.

PMID- 14681828
TI  - Identification and functional analysis of ZIC3 mutations in heterotaxy and
      related congenital heart defects.
AB  - Mutations in the zinc finger transcription factor ZIC3 cause X-linked heterotaxy
      and have also been identified in patients with isolated congenital heart disease
      (CHD). To determine the relative contribution of ZIC3 mutations to both
      heterotaxy and isolated CHD, we screened the coding region of ZIC3 in 194
      unrelated patients, including 61 patients with classic heterotaxy, 93 patients
      with heart defects characteristic of heterotaxy, and 11 patients with situs
      inversus totalis. Five novel ZIC3 mutations in three classic heterotaxy kindreds
      and two sporadic CHD cases were identified. None of these alleles was found in 97
      ethnically matched control samples. On the basis of these analyses, we conclude
      that the phenotypic spectrum of ZIC3 mutations should be expanded to include
      affected females and CHD not typical for heterotaxy. This screening of a cohort
      of patients with sporadic heterotaxy indicates that ZIC3 mutations account for
      approximately 1% of affected individuals. Missense and nonsense mutations were
      found in the highly conserved zinc finger-binding domain and in the N-terminal
      protein domain. Functional analysis of all currently known ZIC3 point mutations
      indicates that mutations in the putative zinc finger DNA binding domain and in
      the N-terminal domain result in loss of reporter gene transactivation. It is
      surprising that transfection studies demonstrate aberrant cytoplasmic
      localization resulting from mutations between amino acids 253-323 of the ZIC3
      protein, indicating that the pathogenesis of a subset of ZIC3 mutations results
      at least in part from failure of appropriate nuclear localization. These results
      further expand the phenotypic and genotypic spectrum of ZIC3 mutations and
      provide initial mechanistic insight into their functional consequences.

PMID- 14681829
TI  - Antisense-induced multiexon skipping for Duchenne muscular dystrophy makes more
      sense.
AB  - Dystrophin deficiency, which leads to severe and progressive muscle degeneration
      in patients with Duchenne muscular dystrophy (DMD), is caused by frameshifting
      mutations in the dystrophin gene. A relatively new therapeutic strategy is based
      on antisense oligonucleotides (AONs) that induce the specific skipping of a
      single exon, such that the reading frame is restored. This allows the synthesis
      of a largely functional dystrophin, associated with a milder Becker muscular
      dystrophy phenotype. We have previously successfully targeted 20 different DMD
      exons that would, theoretically, be beneficial for >75% of all patients. To
      further enlarge this proportion, we here studied the feasibility of double and
      multiexon skipping. Using a combination of AONs, double skipping of exon 43 and
      44 was induced, and dystrophin synthesis was restored in myotubes from one
      patient affected by a nonsense mutation in exon 43. For another patient, with an
      exon 46-50 deletion, the therapeutic double skipping of exon 45 and 51 was
      achieved. Remarkably, in control myotubes, the latter combination of AONs caused
      the skipping of the entire stretch of exons from 45 through 51. This in-frame
      multiexon skipping would be therapeutic for a series of patients carrying
      different DMD-causing mutations. In fact, we here demonstrate its feasibility in
      myotubes from a patient with an exon 48-50 deletion. The application of multiexon
      skipping may provide a more uniform methodology for a larger group of patients
      with DMD.

PMID- 14681830
TI  - Maternally inherited aminoglycoside-induced and nonsyndromic deafness is
      associated with the novel C1494T mutation in the mitochondrial 12S rRNA gene in a
      large Chinese family.
AB  - We report here the characterization of a large Chinese family with maternally
      transmitted aminoglycoside-induced and nonsyndromic deafness. In the absence of
      aminoglycosides, some matrilineal relatives in this family exhibited late
      onset/progressive deafness, with a wide range of severity and age at onset.
      Notably, the average age at onset of deafness has changed from 55 years
      (generation II) to 10 years (generation IV). Clinical data reveal that the
      administration of aminoglycosides can induce or worsen deafness in matrilineal
      relatives. The age at the time of drug administration appears to be correlated
      with the severity of hearing loss experienced by affected individuals. Sequence
      analysis of mitochondrial DNA in this pedigree identified a homoplasmic C-to-T
      transition at position 1494 (C1494T) in the 12S rRNA gene. The C1494T mutation is
      expected to form a novel U1494-1555A base pair, which is in the same position as
      the C1494-1555G pair created by the deafness-associated A1555G mutation, at the
      highly conserved A site of 12S rRNA. Exposure to a high concentration of
      paromomycin or neomycin caused a variable but significant average increase in
      doubling time in lymphoblastoid cell lines derived from four symptomatic and two
      asymptomatic individuals in this family carrying the C1494T mutation when
      compared to four control cell lines. Furthermore, a significant decrease in the
      rate of total oxygen consumption was observed in the mutant cell lines. Thus, our
      data strongly support the idea that the A site of mitochondrial 12S rRNA is the
      primary target for aminoglycoside-induced deafness. These results also strongly
      suggest that the nuclear background plays a role in the aminoglycoside
      ototoxicity and in the development of the deafness phenotype associated with the
      C1494T mutation in the mitochondrial 12S rRNA gene.

PMID- 14681831
TI  - The burden of genetic disease on inpatient care in a children's hospital.
AB  - The important role of genetics in pediatric illness has been increasingly
      recognized, but the true impact has not been well delineated. An important study
      of pediatric inpatient admissions to a children's hospital in 1978 found a
      genetic basis for disease in just less than half of admitted patients. We sought
      to update this study in light of current hospitalization practices and new
      knowledge about genetics. We systematically reviewed the records of 5,747
      consecutive admissions (4,224 individuals), representing 98% of patients admitted
      in 1996 to Rainbow Babies and Children's Hospital (Cleveland, OH). Each patient
      was assigned to one of five groups on the basis of the presence or absence of an
      underlying chronic medical condition and whether that condition had a genetic
      basis or susceptibility. An underlying disorder with a significant genetic
      component was found in 71% of admitted children. The vast majority (96%) of
      underlying chronic disorders in children in this study were either clearly
      genetic or had a genetic susceptibility. Total charges for 1996 were >$62
      million, of which $50 million (81%) was accounted for by disorders with a genetic
      determinant. The 34% of admissions with clearly genetic underlying disorders
      accounted for 50% (>$31 million) of the total hospital charges. The mean length
      of stay was 40% longer for individuals with an underlying disease with a genetic
      basis than for those with no underlying disease. Charges and length of stay were
      similar for children with underlying chronic disorders, regardless of the cause.
      This study begins to quantify the enormous impact of genetic disease on inpatient
      pediatrics and the health care system. Additional study and frank public
      discourse are needed to understand the implications on the future health care
      workforce and on the utilization of health care resources.

PMID- 14681832
TI  - Evidence for extensive transmission distortion in the human genome.
AB  - It is a basic principle of genetics that each chromosome is transmitted from
      parent to offspring with a probability that is given by Mendel's laws. However,
      several known biological processes lead to skewed transmission probabilities
      among surviving offspring and, therefore, to excess genetic sharing among
      relatives. Examples include in utero selection against deleterious mutations,
      meiotic drive, and maternal-fetal incompatibility. Although these processes
      affect our basic understanding of inheritance, little is known about their
      overall impact in humans or other mammals. In this study, we examined genome
      screen data from 148 nuclear families, collected without reference to phenotype,
      to look for departures from Mendelian transmission proportions. Using single
      point and multipoint linkage analysis, we detected a modest but significant
      genomewide shift towards excess genetic sharing among siblings (average sharing
      of 50.43% for the autosomes; P=.009). Our calculations indicate that many loci
      with skewed transmission are required to produce a genomewide shift of this
      magnitude. Since transmission distortion loci are subject to strong selection,
      this raises interesting questions about the evolutionary forces that keep them
      polymorphic. Finally, our results also have implications for mapping disease
      genes and for the genetics of fertility.

PMID- 14681833
TI  - Ethnic differences in adiponectin levels.
AB  - Adiponectin levels were measured in African American and Caucasian women of
      varying body mass index (BMI). Plasma adiponectin levels were compared and the
      relationship between adiponectin and insulin sensitivity was assessed.
      Adiponectin levels were similar in the Caucasian obese (7.0 +/- 0.8 microg/mL),
      African American obese (7.3 +/- 3.5 microg/mL), and African American non-obese
      women (7.1 +/- 1.2 microg/mL), but were significantly higher in Caucasian non
      obese women (12.2 +/- 1.4 microg/mL). Correlational analyses demonstrated that
      BMI, insulin, and homeostasis model assessment (HOMA) correlated significantly
      with adiponectin levels in only the Caucasian women. These results provide
      support for the notion that what applies to other ethnic populations might not
      apply to the African American population, and that the association between
      adiponectin and insulin sensitivity needs to be clarified in the African American
      population.

PMID- 14681834
TI  - Short-term administration of isotretinoin elevates plasma triglyceride
      concentrations without affecting insulin sensitivity in healthy humans.
AB  - The mechanism underlying hypertriglyceridemia-associated insulin resistance in
      humans remains poorly understood. It has been proposed that hypertriglyceridemia
      only produces insulin resistance when associated with an increased lipid delivery
      to muscle. Accordingly, hypertriglyceridemia secondary to a decreased clearance
      of triglyceride-rich particles should not cause insulin resistance. To verify
      this hypothesis, we assessed whole body and adipose tissue insulin sensitivity in
      15 healthy male volunteers before and after a 5-day administration of
      isotretinoin (1 mg/kg/d), a vitamin A derivative that decreases the clearance of
      triglyceride-rich particles. Whole body insulin-mediated glucose disposal (6,6
      (2)H(2)glucose), glucose oxidation (indirect calorimetry), lipolysis ((2)H(5)
      glycerol), and subcutaneous adipose lipolysis (microdialysis) were evaluated
      during a 3-step hyperinsulinemic euglycemic clamp. Isotretinoin increased plasma
      triglyceride from 0.97 +/- 0.15 to 1.30 +/- 0.22 mmol/L (P <.02), but did not
      change whole body insulin-mediated glucose disposal and lipolysis. These
      observations are consistent with an isotretinoin-induced inhibition of very-low
      density lipoprotein (VLDL)-triglyceride clearance. The suppression of endogenous
      glucose production and the reduction in subcutaneous adipose glycerol
      concentrations by insulin remained equally unaffected after isotretinoin
      administration. We conclude that the impaired clearance of triglyceride-rich
      particles secondary to a 5-day isotretinoin administration does not impair
      insulin-mediated antilipolysis or glucose disposal. The data support the concept
      that hypertriglyceridemia-associated insulin resistance develops primarily when
      triglyceride production is increased.

PMID- 14681835
TI  - Does peroxisome proliferator-activated receptor gamma genotype (Pro12ala) modify
      the association of physical activity and dietary fat with fasting insulin level?
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) has a role in
      controlling adipogenesis and insulin sensitivity. Previous studies have suggested
      that a common polymorphism (Pro12Ala) in the PPARgamma-2 isoform of this gene may
      be associated with markers of insulin resistance. We have previously shown that
      in combination, the relationships with fasting insulin of dietary polyunsaturated
      to saturated fatty acid ratio (P:S ratio) and physical activity are additive. We
      have also demonstrated that the association between P:S ratio and fasting insulin
      level is modified by the Pro12Ala genotype. The purpose of the present study was
      to investigate whether the Pro12Ala genotype modified the combined relationships
      of P:S ratio and physical activity level (PAL) on fasting insulin concentration.
      A population-based cohort of 506 Caucasian men and women aged 31 to 71 years was
      genotyped for the Pro12Ala polymorphism. P:S ratio was assessed by food-frequency
      questionnaire (FFQ) and PAL was estimated from 4 days of free-living heart rate
      monitoring following individual calibration of heart rate against energy
      expenditure during an exercise stress test. The combined associations of PAL and
      P:S ratio on fasting insulin level were examined stratified by Pro12Ala genotypes
      in a dominant model for the Ala allele. Among Pro allele homozygotes, there was
      no interaction between PAL and P:S ratio on fasting insulin (P =.929). However,
      in carriers of the Ala allele the association of P:S ratio with fasting insulin
      was modified by activity level (interaction P = 0.038). In those who were
      inactive and carried the Ala allele, the age-, sex-, and body mass-adjusted
      relationship between P:S ratio and log insulin was not significant (beta = -0.03,
      P =.93). In contrast, in physically active Ala carriers, the association of P:S
      ratio with log fasting insulin was highly significant (beta = -0.93, P =.004). In
      conclusion, this study examined the modification by PPARgamma genotype of the
      association between energy expenditure, P:S ratio, and fasting insulin level, a
      measure of insulin resistance. These data show that in Pro allele homozygotes the
      combined associations of P:S ratio and PAL are additive. In contrast, in Ala
      allele carriers, PAL modifies the association between P:S ratio and fasting
      insulin level in a multiplicative manner.

PMID- 14681836
TI  - Leukocyte ABCA1 gene expression is associated with fasting glucose concentration
      in normoglycemic men.
AB  - Adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) mediates the
      efflux of cholesterol to apolipoprotein A1, a process necessary for high-density
      lipoprotein (HDL) formation and reverse cholesterol transport. In patients with
      Tangier disease, mutations in ABCA1 result in low circulating HDL-cholesterol and
      predisposition to coronary heart disease (CHD). ABCA1 gene expression is
      decreased in diabetic mice. In humans, glycated hemoglobin (HbA(1c)) predicted
      future CHD events, even within the normal range. We hypothesised that leukocyte
      ABCA1 gene expression would be inversely associated with indices of glycemia in
      normoglycemic men. Fasting blood samples were taken from 32 healthy, nonsmoking,
      normoglycemic men (age 23 to 46 years). ABCA1, peroxisome proliferator-activated
      receptor gamma (PPARgamma), and liver X receptor alpha (LXRalpha) gene
      expressions in circulating leukocytes were measured using TaqMan technology.
      Significant inverse associations between ABCA1 gene expression and both fasting
      glucose concentration (r = -0.49, P =.008) and age (r = -0.39, P =.043) were
      found. There was no association with HbA(1c) (r = -0.23, P =.238) or HDL
      cholesterol concentration (r = 0.02, P =.904). In a multiple regression model,
      fasting glucose remained a significant independent predictor (P =.037), whereas
      age did not (P =.226). Mechanisms underlying the association were explored; there
      were no significant associations between fasting glucose concentration and
      leukocyte PPARgamma gene expression, or between fasting glucose concentration and
      leukocyte LXRalpha gene expression. This is the first demonstration of an
      association between ABCA1 gene expression and fasting glucose concentration in
      vivo.

PMID- 14681837
TI  - The effect of nitric oxide synthase inhibitor on improved insulin action by
      pioglitazone in high-fructose-fed rats.
AB  - The present study was performed to investigate whether nitric oxide synthase
      (NOS) inhibition influences the increased whole-body insulin action by
      pioglitazone in high-fructose-fed rats. Male Wistar rats aged 6 weeks were
      randomly divided into 3 groups and each group was fed one of the following diets
      for 3 weeks: standard chow diet (control group), high-fructose diet (fructose-fed
      group), and high-fructose diet plus pioglitazone (pioglitazone-treated group).
      The control and pioglitazone-treated groups were further divided into 2 subgroups
      respectively, and some rats of each subgroup were infused the NOS inhibitor, N(G)
      monomethyl-l-arginine (L-NMMA), during the euglycemic clamp studies. In vivo
      insulin action was determined by the 2-step (3 and 30 mU/kg body weight [BW]/min
      low- and high-dose, respectively) hyperinsulinemic euglycemic clamp procedure in
      the awake condition. Glucose infusion rate (GIR) was considered as the index of
      insulin action. Endothelium-type NOS (eNOS) and inducible NOS (iNOS) in skeletal
      muscle were also measured. At the low-dose clamp, high-fructose feeding produced
      a marked decrease in GIR compared with the control group. Pioglitazone-treated
      animals showed a significant increase in GIR, reaching a similar level as the
      control group. However, the improved GIR was decreased to the level of the
      fructose-fed group by L-NMMA infusion. The GIR of the control group was not
      affected by L-NMMA infusion. The same tendency as the low-dose clamp was found at
      the high-dose clamp. In skeletal muscle, eNOS and iNOS protein content were not
      affected by high-fructose feeding and/or pioglitazone treatment. These results
      suggest that NOS inhibition can decrease the improved insulin resistance by
      pioglitazone in high-fructose-fed rats. Therefore, although NOS protein content
      is not changed by high-fructose feeding and/or pioglitazone treatment, it could
      be concluded that nitric oxide (NO) plays an important role in the improvement of
      insulin action by pioglitazone.

PMID- 14681838
TI  - Effects of food restriction on peroxisome proliferator-activated receptor-gamma
      and glucocorticoid receptor signaling in adipose tissues of normal rats.
AB  - In adipocytes, peroxisome proliferator-activated receptor (PPAR)-gamma activates
      adipocyte differentiation and glucocorticoid (GC) stimulates the expression of
      PPAR-gamma mRNA. The local tissue concentrations of GC, in turn, are modulated by
      11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). To clarify the change
      of energy metabolism in condition of reduced energy intake, we investigated
      whether food restriction alters the adipocyte size and levels of PPAR-gamma, GC
      receptor (GR), and 11beta-HSD1 mRNA expression in the white adipose tissues of
      normal rats. Male Wistar rats weighing 340 g were housed under free feeding or
      20% reduction of food intake for 2 or 14 days. We found that 2-day food
      restriction did not cause any change in the mean size or number of adipocytes in
      the omentum, while 14-day food restriction decreased the size and increased the
      number of adipocytes. In addition, the levels of PPAR-gamma2, GR, and 11beta-HSD1
      mRNA expression in the omentum were lower in the food-restricted rats after 2
      days, while they did not differ after 14 days. Also, after both 2 and 14 days,
      plasma concentrations of free fatty acid (FFA) were higher in the food-restricted
      rats than in control rats. Finally, plasma concentrations of adrenocorticotropin
      (ACTH) and corticosterone were the same in the both groups after 2 days, although
      they were higher in the food-restricted rats after 14 days. These results suggest
      that adipocyte differentiation in the omentum of food-restricted rats is
      attenuated after 2 days but recovers after 14 days, resulting in an increase in
      the number of small adipocytes. It is also likely that lipolysis induced during
      the 14-day period of food restriction decreased the size of adipocytes. Further,
      food restriction may affect the efficiency of local GC effects by altering GR and
      11beta-HSD1 mRNA expression. Also, higher levels of plasma GC and recovery of GR
      and 11beta-HSD1 mRNA expression may contribute to the recovery of the levels of
      PPAR-gamma2 mRNA expression in the omentum and result in the recovery of
      adipocyte differentiation.

PMID- 14681839
TI  - Copper enzyme activities in cystic fibrosis before and after copper
      supplementation plus or minus zinc.
AB  - One laboratory reports low activities for 2 blood copper enzymes in subjects with
      cystic fibrosis (CF), which suggests that moderate copper deficiency is common in
      this state. The present study attempted to confirm this proposition in 3 ways:
      repeat the measures for 1 of the 2 copper enzymes (superoxide dismutase) in a new
      group of CF patients (males and females, N = 38), add another copper enzyme
      measure (plasma diamine oxidase) that has high sensitivity to copper status, and
      test if copper enzyme activities in CF patients rise by copper supplementation.
      The last test was performed plus or minus zinc supplementation since poor zinc
      status may contribute to poor copper status. The results for the first 2 aims
      supported the idea of poor copper status, as low activities were found for CF
      subjects for 2 copper enzyme activities, erythrocyte superoxide dismutase and
      plasma diamine oxidase (although normal activities were obtained for another
      copper enzyme, plasma ceruloplasmin, both as U/mL plasma or U/mg ceruloplasmin
      immunoreactive protein). For the last aim, copper enzyme activities were not
      altered by copper supplementation (6 weeks, 3 mg copper/d as copper-glycinate),
      plus or minus concurrent zinc supplementation (30 mg zinc/d as zinc-glycinate).
      Therefore, CF may cause a tendency to moderate copper deficiency, which may be
      due to abnormal copper metabolism not easily corrected by increased copper and/or
      zinc intake.

PMID- 14681840
TI  - Significance of plasma 7alpha-hydroxy-4-cholesten-3-one and 27-hydroxycholesterol
      concentrations as markers for hepatic bile acid synthesis in cholesterol-fed
      rabbits.
AB  - Plasma 7alpha-hydroxy-4-cholesten-3-one has been used as an index of hepatic bile
      acid synthesis. The aim of the current study was to ascertain whether the level
      of this oxysterol reflects hepatic cholesterol 7alpha-hydroxylase activity when
      plasma cholesterol concentrations are markedly changed. In addition, the
      relationship of hepatic sterol 27-hydroxylase activity with plasma concentrations
      of 27-hydroxycholesterol and 3beta-hydroxy-5-cholestenoic acid was studied. We
      used New Zealand white rabbits fed 2% cholesterol for 5 or 10 days and/or
      constructed bile fistula. Feeding cholesterol markedly increased and bile
      drainage reduced plasma cholesterol concentrations. Initially, in these models
      there was no correlation between plasma 7alpha-hydroxy-4-cholesten-3-one
      concentrations and hepatic cholesterol 7alpha-hydroxylase activities (r = -0.24,
      n = 10). Cholesterol feeding was associated with downregulated 7alpha-hydroxylase
      activities, while plasma 7alpha-hydroxy-4-cholesten-3-one concentrations were
      elevated in the presence of increased plasma cholesterol levels. However, this
      discrepancy was overcome and significant correlation was observed (r = 0.73, P
      <.05, n = 10) by expressing 7alpha-hydroxy-4-cholesten-3-one levels relative to
      cholesterol. In contrast, hepatic sterol 27-hydroxylase activities were not
      significantly correlated with plasma absolute (r = 0.23, difference not
      significant [NS], n = 10) nor cholesterol-related levels of 27-hydroxycholesterol
      (r = -0.13, NS, n = 10), or 3beta-hydroxy-5-cholestenoic acid concentrations (r =
      0.30, NS, n = 10). In conclusion, plasma 7alpha-hydroxy-4-cholesten-3-one
      concentrations reflected hepatic cholesterol 7alpha-hydroxylase activities when
      the sterol levels were adjusted to plasma cholesterol concentrations in rabbits
      with hypercholesterolemia. The results suggest that plasma 7alpha-hydroxy-4
      cholesten-3-one relative to cholesterol is a better marker for hepatic
      cholesterol 7alpha-hydroxylase activity than the absolute concentration when
      hypercholesterolemia is present. In contrast, 27-hydroxycholesterol and 3beta
      hydroxy-5-cholestenoic acid levels in plasma did not reflect hepatic sterol 27
      hydroxylase activities even if the levels were adjusted to plasma cholesterol
      concentrations.

PMID- 14681841
TI  - Daytime triglyceridemia in normocholesterolemic patients with premature
      atherosclerosis and in their first-degree relatives.
AB  - Postprandial hypertriglyceridemia tested under metabolic ward conditions with
      unphysiological high fat loads has been reported in CAD patients and their
      relatives even in the presence of normal fasting lipids. It is unclear whether
      this also occurs in the daytime situation. Twenty-seven normocholesterolemic, non
      obese and nondiabetic patients with premature coronary artery disease (CAD) and
      56 first-degree relatives without CAD measured daytime capillary triglyceride
      profiles (TGc-AUC) as an estimate of postprandial lipemia. Fasting capillary
      triglycerides (TGc) were not significantly different between CAD index patients
      and their relatives (1.68 +/- 0.63 and 1.54 +/- 0.71 mmol/L, respectively). In
      contrast, daytime triglyceridemia was significantly higher in CAD patients (30.7
      +/- 13.6 mmol. h/L) compared to their relatives (24.4 +/- 9.4 mmol. h/L) and this
      was also the case after correction for fasting TGc (7.24 +/- 7.41 and 2.79 +/-
      6.89 mmol. h/L; P <.05). The best predictors of TGc-AUC by multiple regression
      analysis in CAD families were fasting TGc, systolic blood pressure, and high
      density lipoprotein cholesterol (HDL-C), which are all components of the
      metabolic syndrome, explaining 65% of the variation. Since there were no major
      differences in nutritional intake between index patients and their relatives,
      this could not explain the differences Daytime triglyceridemia, measured under
      physiological conditions, is increased in patients with premature atherosclerosis
      and normal fasting TG levels, when compared to their non-CAD relatives. This
      study confirms previous observations using standardized oral fat loading tests
      and underlines the importance of postprandial hyperlipidemia in CAD.

PMID- 14681842
TI  - Oral modified insulin (HIM2) in patients with type 1 diabetes mellitus: results
      from a phase I/II clinical trial.
AB  - An effective, orally administered insulin product would be of substantial benefit
      in the treatment of patients with diabetes mellitus. This phase I/II clinical
      trial was the first to investigate the safety and effectiveness of a single oral
      dose of a modified human insulin in controlling postprandial plasma glucose
      levels in patients with type 1 diabetes mellitus who were receiving basal
      continuous subcutaneous insulin infusion (CSII) therapy. Fourteen patients with
      type 1 diabetes mellitus were evaluated in an open-label, 2-center, dose
      escalation, nonrandomized study of oral hexyl-insulin monoconjugate 2 (HIM2).
      After an overnight fast and prior to receiving a standardized meal (50%
      carbohydrates, 30% fat, 20% proteins; 650 calories), the patients received either
      no additional insulin (day 1), or 0.5 to 1.0 mg/kg of HIM2 (day 2). All patients
      received a basal insulin regimen by CSII throughout the study. Blood samples were
      collected for determination of glucose and insulin levels for 240 minutes post
      dose. The postprandial glucose excursion versus time curves showed clear
      reductions in glucose values after both HIM2 doses (day 2) relative to no
      treatment (day 1), although the differences in the reductions were not
      statistically significant. When the data for both HIM2 doses were pooled, a
      statistically significant effect of HIM2 on glucose excursion (as measured by
      AUCex(30-240)) was observed. Mean +/- SD values for AUCex(30-240) were 501.35 +/-
      124.1 mg. h/dL after no treatment and 375.81 +/- 215.5 mg. h/dL after HIM2
      (Wilcoxon signed-rank test, P =.042). The results of this study suggest that oral
      HIM2, when added to a basal insulin regimen, was safe and may prove effective in
      controlling postprandial hyperglycemia in patients with type 1 diabetes mellitus.
      Further clinical investigation is necessary.

PMID- 14681843
TI  - Effects of different dietary oils on inflammatory mediator generation and fatty
      acid composition in rat neutrophils.
AB  - Virgin olive oil (VOO) compared with fish oil (FO) and evening primrose oil (PO)
      on the ability of stimulated leukocytes to produce inflammatory mediators was
      investigated in rats. Weaned Wistar rats were fed a basal diet (BD) (2% by weight
      of corn oil) or diets containing 15% by weight of VOO, PO, or FO. After 8 weeks,
      glycogen-elicited peritoneal polymorphonuclear leukocytes, mainly neutrophils,
      were isolated. The calcium-ionophore stimulated neutrophils (2.5 x 10(6)
      cells/mL) obtained from rats fed the different oils produced a higher release of
      lysosomal enzymes (beta-glucuronidase, lysozyme, and myeloperoxidase [MPO])
      compared with those fed BD. The production of reactive oxygen species (ROS) in
      response to the stimulant, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), by
      neutrophils from the VOO group (15.44 nmol of O(2)(-) and 6.56 nmol of H(2)O(2))
      was similar to the BD group (12.01 nmol O(2)(-) and 8.49 nmol H(2)O(2)) and
      significantly lower than the PO (20.90 nmol O(2)(-) and 10.84 nmol H(2)O(2)) and
      FO (20.93 nmol O(2)(-) and 12.79 nmol H(2)O(2)) groups. The cyclooxygenase
      derived eicosanoid production was reduced by the lipid enrichment of the diets.
      Whereas the generation of prostaglandin E(2) (PGE(2)) was significantly decreased
      in VOO (5.40 ng/mL), PO (4.95 ng/mL), and FO (1.44 ng/mL) groups compared with BD
      (8.19 ng/mL), thromboxane B(2) (TXB(2)) reduction was especially significant in
      neutrophils from the FO diet group (14.67 ng/mL compared with 26.69 ng/mL from
      BD). These experimental data suggest that FO and PO, as well as VOO, could be
      considered a valuable strategy in preventing the generation of some inflammatory
      mediators.

PMID- 14681844
TI  - The role of adenosine triphosphate citrate lyase in the metabolism of acetyl
      coenzyme a and function of blood platelets in diabetes mellitus.
AB  - Diabetes is known to increase blood platelet activity. Activities of pyruvate
      dehydrogenase (PDH), adenosine triphosphate (ATP)-citrate lyase (ATPCL), acetyl
      coenzyme A (acetyl-CoA) content, malonyl dialdehyde (MDA), synthesis, and
      platelet aggregation in resting conditions and after activation with thrombin
      were measured in diabetic subjects and in age- and sex-matched healthy subjects.
      Activities of ATPCL and PDH, acetyl-CoA content, and thrombin-evoked MDA
      synthesis as well as platelet aggregation in diabetes were 31%, 51%, 62%, 35%,
      and 21%, respectively, higher than in healthy subjects. In addition, activation
      of diabetic platelets caused 2 times greater release of acetyl-CoA from their
      mitochondria than in controls. Both 1.0 mmol/L (-)hydroxycitrate and 0.1 mmol/L
      SB-204490 decreased acetyl-CoA content in platelet cytoplasm along with
      suppression of MDA synthesis and platelet aggregation. These inhibitory effects
      were about 2 times greater in diabetic than in control platelets. The data
      presented indicate that the ATPCL pathway is operative in human platelets and may
      be responsible for provision of about 50% of acetyl units from their
      mitochondrial to cytoplasmic compartment. Increased acetyl-CoA synthesis in
      diabetic platelets may be the cause of their excessive activity in the course of
      the disease. ATPCL may be a target for its specific inhibitors as factors
      decreasing platelet activity.

PMID- 14681845
TI  - Antihyperglycemic effects of stevioside in type 2 diabetic subjects.
AB  - Stevioside is present in the plant Stevia rebaudiana Bertoni (SrB). Extracts of
      SrB have been used for the treatment of diabetes in, for example, Brazil,
      although a positive effect on glucose metabolism has not been unequivocally
      demonstrated. We studied the acute effects of stevioside in type 2 diabetic
      patients. We hypothesize that supplementation with stevioside to a test meal
      causes a reduction in postprandial blood glucose. Twelve type 2 diabetic patients
      were included in an acute, paired cross-over study. A standard test meal was
      supplemented with either 1 g of stevioside or 1 g of maize starch (control).
      Blood samples were drawn at 30 minutes before and for 240 minutes after ingestion
      of the test meal. Compared to control, stevioside reduced the incremental area
      under the glucose response curve by 18% (P =.013). The insulinogenic index
      (AUC(i,insulin)/AUC(i,glucose)) was increased by approximately 40% by stevioside
      compared to control (P <.001). Stevioside tended to decrease glucagon levels,
      while it did not significantly alter the area under the insulin, glucagon-like
      peptide 1, and glucose-dependent insulinotropic polypeptide curves. In
      conclusion, stevioside reduces postprandial blood glucose levels in type 2
      diabetic patients, indicating beneficial effects on the glucose metabolism.
      Stevioside may be advantageous in the treatment of type 2 diabetes.

PMID- 14681846
TI  - Ethanol with a mixed meal decreases the incretin levels early postprandially and
      increases postprandial lipemia in type 2 diabetic patients.
AB  - Increased postprandial lipemia is a risk marker of cardiovascular disease (CVD).
      While moderate alcohol drinking is associated with a reduced risk of CVD in
      nondiabetic and type 2 diabetic patients, it is also known that alcohol increases
      postprandial triacylglycerol levels. The incretins, glucose-dependent
      insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), are
      important hormones from the gut that enhance nutrient-stimulated insulin
      secretion. Their responses to a moderate alcohol dose in type 2 diabetes have not
      previously been studied. We sought to determine how alcohol influences
      postprandial lipid and incretin levels in patients with type 2 diabetes when
      taken in combination with a fat-rich mixed meal. Eleven patients with type 2
      diabetes ingested on 3 separate days in random order 3 different meals
      containing: 100 g butter alone or 100 g butter in combination with 40 g alcohol
      and 50 g carbohydrate, or 100 g butter and 120 g carbohydrate. The meal with
      alcohol and 50 g carbohydrate was isocaloric to that of 120 g carbohydrate.
      Triacylglycerol levels were measured after separation by ultracentrifugation into
      a chylomicron-rich fraction with Svedberg flotation unit values (Sf) > 1,000, and
      a chylomicron-poor fraction with Sf < 1,000. Supplementation of a fat-rich mixed
      meal with alcohol in type 2 diabetic subjects suppressed GLP-1 early in the
      postprandial phase and increased the late triacylglycerol responses compared with
      the 2 other meals. In the chylomicron-rich fraction, both triacylglycerol and
      cholesterol were increased by alcohol. No significant differences in high-density
      lipoprotein (HDL)-cholesterol levels were seen. Isocaloric amounts of
      carbohydrate and alcohol suppressed equally the postprandial free fatty acid
      levels, but carbohydrate increased the postprandial glucose, GIP, and insulin
      levels the most. Early in the postprandial phase, alcohol suppresses the incretin
      responses and increases the late postprandial triacylglycerol levels in type 2
      diabetic patients. Whether this reflects an alcohol-induced suppression of the
      incretin response, which adds to the alcohol-induced impairment of
      triacylglycerol clearance in type 2 diabetic patients, remains to be elucidated.

PMID- 14681847
TI  - Upregulation of ghrelin expression in cachectic nude mice bearing human melanoma
      cells.
AB  - Ghrelin is a gastrointestinal peptide that stimulates food intake and growth
      hormone (GH) secretion. We studied the biosynthesis and secretion of ghrelin in a
      cancer cachexia mouse model. G361, a human melanoma cell line, was inoculated
      into nude mice. The body weight was reduced and the plasma concentration of
      interleukin-1beta (IL-1beta) was markedly higher in tumor-inoculated mice
      compared with vehicle-treated mice. Furthermore, white adipose tissue (WAT)
      weight, blood sugar level, and plasma concentrations of leptin and nonesterified
      fatty acids (NEFA) were significantly lower in tumor-inoculated mice. The plasma
      concentration of ghrelin increased with the progression of cachexia. The levels
      of both ghrelin peptide and mRNA in the stomach were also upregulated in tumor
      inoculated mice. This study demonstrates that both ghrelin biosynthesis and
      secretion are stimulated in the long-term negative energy balance of tumor
      inoculated cachectic mice. These findings suggest the involvement of ghrelin in
      the regulation of energy homeostasis in cancer cachexia.

PMID- 14681848
TI  - Plasma cortisol and cortisone concentrations in normal subjects and patients with
      adrenocortical disorders.
AB  - Two isozymes of the 11beta-hydroxysteroid dehydrogenase (11-HSD) are responsible
      for the interconversion of cortisol (F) and cortisone (E). The type 1 isozyme, 11
      HSD1, acts mainly as a reductase in vivo, activating E to F, whereas the type 2,
      11-HSD2, acts as a dehydrogenase, inactivating F to E. 11-HSD1 is the most
      abundant in the liver and 11-HSD2 in the kidney. In this study, we attempted to
      determine which isozyme and organs primarily contribute to equilibrium of plasma
      F and E concentrations in the peripheral circulation and to clarify differences
      in 11-HSD activities among adrenocortical disorders. Upon selective
      catheterizations for adrenocortical and renovascular disorders, plasma F and E
      concentrations in the femoral vein were closer to those in the renal vein than
      those in the hepatic vein. Values for mean plasma F/E ratios in the peripheral
      vein were in-between those of the adrenal and renal veins. A double reciprocal
      plot between peripheral plasma F and E concentrations in patients with various
      adrenocortical tumors was almost identical to that in normal subjects. Mean
      plasma F/E ratio in peripheral blood was higher in patients with Cushing's
      syndrome and was lower in patients with primary aldosteronism and nonfunctioning
      adrenocortical adenoma than that in normal subjects. These results suggest that
      renal 11-HSD2 is a main factor controlling the equilibrium of plasma F and E
      concentrations in the periphery and that cortisol and aldosterone excess do not
      change the equilibrium of plasma F and E concentrations in the peripheral
      circulation, but may alter expression of 11-HSD2. Alternation of 11-HSD2
      activities as well as corticosteroid levels may be important in the
      pathophysiology of adrenocortical disorders.

PMID- 14681849
TI  - Circulating blood cells modulate the atherosclerotic process in apolipoprotein E
      deficient mice.
AB  - The interaction of blood with the arterial tree may play an important role in the
      development of atherosclerotic lesions. The aims of this study were (1) to
      determine how anemia or increased hematocrit affect the development of
      atherosclerosis and (2) to find relationships between hematologic and
      hemorrheologic variables in apolipoprotein (apo) E-deficient mice. Forty-two mice
      were randomly divided into 3 groups of 14 mice each. There was no further
      manipulation in the control group. To induce anemia, the mice from one of the
      groups were repeatedly bled, drawing approximately 250 microL blood from each
      mouse twice a week. To increase the hematocrit levels in another group of mice,
      we injected 20 U recombinant human erythropoietin every other day. The
      development of lesions and the main variables involved in atherogenesis were
      compared among groups. Our results show that atherosclerosis was attenuated in
      the mice that were bled, and this was not accounted for by changes in plasma
      lipid levels, the distribution of lipoprotein particles, the body iron
      distribution, or oxidation parameters. Moreover, atherosclerosis was enhanced in
      the mice treated with the continuous administration of erythropoietin. To
      ascertain the relationship between hematocrit and whole blood viscosity, we
      measured both variables in pooled blood from 24 additional mice, which were
      manipulated to ensure a wide range of values. We found a direct and significant
      correlation between hematocrit and blood viscosity and between hematocrit and
      lesion size. Our data support in vivo the idea that hemorrheology has an
      important role in atherogenesis in this particular animal model.

PMID- 14681850
TI  - Effects of stevioside on glucose transport activity in insulin-sensitive and
      insulin-resistant rat skeletal muscle.
AB  - Stevioside (SVS), a natural sweetener extracted from Stevia rebaudiana, has been
      used as an antihyperglycemic agent. However, little is known regarding its
      potential action on skeletal muscle, the major site of glucose disposal.
      Therefore, the purpose of the present study was to determine the effect of SVS
      treatment on skeletal muscle glucose transport activity in both insulin-sensitive
      lean (Fa/-) and insulin-resistant obese (fa/fa) Zucker rats. SVS was administered
      (500 mg/kg body weight by gavage) 2 hours before an oral glucose tolerance test
      (OGTT). Whereas the glucose incremental area under the curve (IAUC(glucose)) was
      not affected by SVS in lean Zucker rats, the insulin incremental area under the
      curve (IAUC(insulin)) and the glucose-insulin index (product of glucose and
      insulin IAUCs and inversely related to whole-body insulin sensitivity) were
      decreased (P<.05) by 42% and 45%, respectively. Interestingly, in the obese
      Zucker rat, SVS also reduced the IAUC(insulin) by 44%, and significantly
      decreased the IAUC(glucose) (30%) and the glucose-insulin index (57%). Muscle
      glucose transport was assessed following in vitro SVS treatment. In lean Zucker
      rats, basal glucose transport in type I soleus and type IIb epitrochlearis
      muscles was not altered by 0.01 to 0.1 mmol/L SVS. In contrast, 0.1 mmol/L SVS
      enhanced insulin-stimulated (2 mU/mL) glucose transport in both epitrochlearis
      (15%) and soleus (48%). At 0.5 mmol/L or higher, the SVS effect was reversed.
      Similarly, basal glucose transport in soleus and epitrochlearis muscles in obese
      Zucker rats was not changed by lower doses of SVS (0.01 to 0.1 mmol/L). However,
      these lower doses of SVS significantly increased insulin-stimulated glucose
      transport in both obese epitrochlearis and soleus (15% to 20%). In conclusion,
      acute oral SVS increased whole-body insulin sensitivity, and low concentrations
      of SVS (0.01 to 0.1 mmol/L) modestly improved in vitro insulin action on skeletal
      muscle glucose transport in both lean and obese Zucker rats. These results
      indicate that one potential site of action of SVS is the skeletal muscle glucose
      transport system.

PMID- 14681851
TI  - Association of apolipoprotein E polymorphism with blood lipids and maximal oxygen
      uptake in the sedentary state and after exercise training in the HERITAGE family
      study.
AB  - The relationship of apolipoprotein E (apo E) genotypes to plasma lipid and
      maximal oxygen uptake (Vo(2max)) was studied in the sedentary state and after a
      supervised exercise training program in black and white men and women. At
      baseline, the apo E 2/3 genotype was associated with the lowest, and apo E 3/4
      and E4/4 with the highest low-density liporpotein (LDL) cholesterol and apo B
      levels in men and women of both races, while female (not male) carriers of apo E3
      had higher high-density lipoprotein (HDL) cholesterol levels than carriers of
      other genotypes. Very-low-density lipoprotein (VLDL) cholesterol and triglyceride
      levels were significantly higher in carriers of both apo E2 and apo E4 in white
      men only. Racial and sex differences were noted in lipid responses to exercise
      training across genotypes with a significantly greater increase in HDL
      cholesterol observed only in white female carriers of apo E 2/3 and E3/3, as
      compared to apo E4/4. Apo E polymorphism was not found to be associated with
      Vo(2max) levels either in the sedentary state nor the Vo(2max) response to
      exercise training, contrary to previous reports.

PMID- 14681852
TI  - De novo emergence of growth factor receptors in activated human CD4+ and CD8+ T
      lymphocytes.
AB  - Using phytohemagglutinin (PHA)-activated human T lymphocytes, we have
      demonstrated de novo emergence of growth factor receptors (insulin, insulin-like
      growth factor-1 [IGF-1], and interleukin-2 [IL-2]) in the CD4(+) and CD8(+)
      subsets determined by flow cytometry. This activation was also associated with
      development of insulin-degrading activity (IDA) in a time-dependent fashion.
      These events, which are actinomycin- and cycloheximide-sensitive, occur only in
      activated, but not nonactivated, CD4(+) and CD8(+) lymphocytes. The emergence of
      these receptors, as well as IDA, which is preceded by CD69 emergence, reaches a
      plateau by 72 hours and is comparable in both subsets. The IDA is localized in
      the cytosol, and insulin binding is limited to the cell membrane. T-lymphocyte
      activation also initiates expression of the IL-2 gene with the transcription of
      IL-2 mRNA, the level of which is further enhanced by 38% with the addition of
      insulin. In these activated lymphocytes, insulin binding to its receptor also
      caused an 83% upregulation of phosphorylated insulin receptor substrate-1 (IRS
      1). In situ development of these growth factor receptors and signal transduction
      mechanisms in T lymphocytes upon activation, such as by proinflammatory cytokines
      or oxidative stress, could be an important defense mechanism in various disease
      states in man.

PMID- 14681853
TI  - Absence of correlation between glycated hemoglobin and lipid composition of
      erythrocyte membrane in type 2 diabetic patients.
AB  - Correlation of glycated hemoglobin (HbA(1c)) level with degrees of certain
      peroxidative changes in erythrocyte membrane lipids in diabetic patients have
      been reported. In the present study, peroxidation of erythrocyte lipids was
      assessed by changes in tocopherols (Toc), phospholipids (PL), and malondialdehyde
      (MDA). Membrane cholesterol, Toc, and PL were determined from the same lipid
      extract. Toc and cholesterol were measured simultaneously by high-performance
      liquid chromatography (HPLC), and each PL class was determined by a single HPLC
      elution with ultraviolet light (UV) detection. The detection of PL with UV
      depends primarily on double bonds in fatty acids and shows a decrease in fatty
      acids by peroxidation. Changes in Toc and each PL were calculated on the basis of
      cholesterol and SM, respectively, since cholesterol and sphingomyelin (SM) in the
      cell membrane are not prone to peroxidation. MDA was measured by an HPLC method
      with fluorescence detection. These methods for assessment for peroxidation of
      membrane lipids in intact erythrocytes were validated by experiments with 2, 2
      azobis(2-amidinopropane)dihydrochloride (AAPH) and tert-butylhydroperoxide
      (tBHP); nevertheless, significant differences in the levels of Toc, each PL
      class, and MDA between a high-HbA(1c) group and a low-HbA(1c) group were not
      detected.

PMID- 14681854
TI  - Quantification of DNA synthesis from different pathways in cultured human
      fibroblasts and myocytes.
AB  - We have quantified DNA synthetic rates from different pathways in cultured cells
      using a new stable isotope technique. Human fibroblasts and myocytes were grown
      in culture media supplemented with [U-(13)C(6)]glucose and [(15)N]glycine. The
      cells were sampled daily from day 1 to day 5. A portion of the cells harvested at
      day 5 was subcultured for an additional 3 passages to reach isotopic plateau. In
      both cell types total DNA fractional synthetic rate (FSR) was found to agree
      closely with the rate of cell proliferation determined by cell counting (FSR =
      0.94%. h(-1) v 0.92%. h(-1) for DNA synthesis and cell count, respectively, in
      myocytes and 0.85%. h(-1) v 0.91%. h(-1) for DNA synthesis and cell count,
      respectively, in fibroblasts). In fibroblasts the deoxyribonucleoside salvage
      pathway accounted for over 70% of total DNA synthesis. In myocytes the
      deoxyribonucleoside salvage pathway was minimal, whereas the de novo base
      synthesis pathway accounted for almost 80% of total DNA synthesis. We conclude
      that the contributions of various pathways to DNA synthesis are highly dependent
      on cell type. This new stable isotope technique can be modified for application
      in in vivo studies.

PMID- 14681857
TI  - Low water-soluble uremic toxins.
AB  - The uremic syndrome is the result of the retention of solutes, which under normal
      conditions are cleared by the healthy kidneys. Uremic retention products are
      arbitrarily subdivided according to their molecular weight. Low-molecular-weight
      molecules are characterized by a molecular weight below 500 D. The purpose of the
      present publication is to review the main water soluble, nonprotein bound uremic
      retention solutes, together with their main toxic effects. We will consecutively
      discuss creatinine, glomerulopressin, the guanidines, the methylamines, myo
      inositol, oxalate, phenylacetyl-glutamine, phosphate, the polyamines,
      pseudouridine, the purines, the trihalomethanes, and urea per se.

PMID- 14681858
TI  - Middle molecules and small-molecular-weight proteins in ESRD: properties and
      strategies for their removal.
AB  - Molecular weight has traditionally been the parameter most commonly used to
      classify uremic toxins, with a value of approximately 500 Da frequently used as a
      demarcation point below which the molecular weights of small nitrogenous waste
      products fall. This toxin group, the most extensively studied from a clinical
      perspective, is characterized by a high degree of water solubility and the
      absence of protein binding. However, uremia is mediated by the retention of a
      plethora of other compounds having characteristics that differ significantly from
      those of the previously mentioned group. As opposed to the relative homogeneity
      of the nitrogenous metabolite class, other uremic toxins collectively are a very
      heterogeneous group, not only with respect to molecular weight but also other
      characteristics, such as protein binding and hydrophobicity. A recently proposed
      classification scheme by the European Uraemic Toxin Work Group subdivides the
      remainder of molecules into 2 categories: protein-bound solutes and middle
      molecules. For the latter group, the Work Group proposes a molecular weight range
      (500-60,000 Da) that incorporates many toxins identified since the original
      middle molecule hypothesis, for which the upper molecular weight limit was
      approximately 2,000 Da. In fact, low-molecular-weight peptides and proteins
      (LMWPs) comprise nearly the entire middle molecule category in the new scheme.
      The purpose of this article is to provide an overview of the middle molecule
      class of uremic toxins, with the focus on LMWPs. A brief review of LMWP
      metabolism under conditions of normal (and in a few cases, abnormal) renal
      function will be presented. The physical characteristics of several LMWPs will
      also be presented, including molecular weight, conformation, and charge. Specific
      LMWPs to be covered will include beta 2-microglobulin, complement proteins (C3a
      and Factor D), leptin, and proinflammatory cytokines. The article will also
      include a discussion of the treatment-related factors influencing dialytic
      removal of middle molecules. Once these factors, which include membrane
      characteristics, protein-membrane interactions, and solute removal mechanisms,
      are discussed, an overview of the different therapeutic strategies used to
      enhance clearance of these compounds is provided.

PMID- 14681859
TI  - Beta-2 microglobulin in ESRD: an in-depth review.
AB  - Beta-2 microglobulin is the most widely studied low-molecular-weight protein in
      end-stage renal disease. It is known to cause dialysis-related amyloidosis (DRA),
      by virtue of its retention when renal function fails, its deposition in tissues,
      its aggregation into fibrils, and its ability to become glycosylated. The onset
      of DRA may be protracted by the use of noncellulosic membranes, especially when
      high-volume hemodiafiltration is used in the treatment of renal failure.
      Adsorptive methods have been developed to improve the removal of beta-2
      microglobulin. There seems to be a relative risk reduction in mortality when
      patients are treated with dialysis membranes that have a higher clearance of beta
      2 microglobulin.

PMID- 14681860
TI  - Protein-bound uremic retention solutes.
AB  - Protein-bound uremic retention solutes are molecules with low molecular weight
      (MW) but should be considered middle or high MW substances. This article
      describes the best known substances of this group, which include p-cresol,
      indoxyl sulfate, hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furan-propionic
      acid (CMPF), and homocysteine. At concentrations encountered during uremia, p
      cresol inhibits phagocyte function and decreases leukocyte adhesion to cytokine
      stimulated endothelial cells. CMPF has been implicated in anemia and neurologic
      abnormalities of uremia. CMPF could alter the metabolism of drugs of inhibiting
      their binding to albumin and their tubular excretion. Indoxyl sulfate
      administrated to uremic rats increases the rate of progression of renal failure.
      Hippuric acid inhibits glucose utilization in the muscle, and its serum
      concentration is correlated with neurologic symptoms of uremia. Homocysteine
      predisposes uremic patients to cardiovascular disease through impairment of
      endothelial and smooth muscle cell functions. The removal of protein-bound
      compounds by conventional hemodialysis is low. Other strategies to decrease their
      concentrations include increase in dialyze pore size, daily hemodialysis,
      peritoneal dialysis, reduction of production or acceleration of degradation, and
      preservation of residual renal function.

PMID- 14681861
TI  - Advanced glycation end products in uremia.
AB  - The term "advanced glycation end products" (AGEs) stands for a heterogeneous
      group of amino acid derivatives that are formed via glycation processes between
      peptide-bound lysine or arginine derivatives and carbonyl compounds, processes
      originally known from food systems as "Maillard reactions." AGEs accumulate in
      plasma and tissues with advancing age, diabetes, and particular renal failure. In
      vivo and in vitro studies indicate that AGEs represent an important class of
      uremic toxins. This review focuses on the chemistry behind the formation of AGEs,
      possible mechanisms underlying the accumulation of AGEs in uremia, clinical and
      therapeutic implications, and possible nutritional consequences.

PMID- 14681862
TI  - Leptin, ghrelin, and proinflammatory cytokines: compounds with nutritional impact
      in chronic kidney disease?
AB  - Metabolic and nutritional derangements are prominent features of the uremic
      syndrome. Recent evidence suggest that several large-molecular-weight molecules
      that often are elevated in uremia, such as leptin, ghrelin, and proinflammatory
      cytokines, may have nutritional impact in this patient group. On the basis of
      present knowledge, these compounds could be regarded as suspected but not
      established uremic toxins. The discovery of the ob gene, its product leptin, and
      cerebral leptin receptors has undoubtedly widened our understanding of obesity
      and the underlying molecular and physiologic mechanisms that regulate food intake
      and body weight. Moreover, the recent discovery of leptin receptor isoforms in
      several peripheral organs suggests that leptin besides having a central function
      also has several important peripheral biological functions. Because uremic
      patients in general have an inappropriate elevation of circulatory leptin,
      further research is necessary to determine the potential biological effects of
      elevated leptin levels in end-stage renal disease. Also, because many symptoms
      and findings prevalent in the uremic syndrome are known to be associated with
      elevated levels of proinflammatory cytokines, such as interleukin-6, future
      studies are needed to evaluate the role of specific anti-inflammatory treatment
      strategies in malnourished uremic patients.

PMID- 14681880
TI  - Febrile seizures impair memory and cAMP response-element binding protein
      activation.
AB  - The long-term effects of brief but repetitive febrile seizures (FS) on memory
      have not been as thoroughly investigated as the impact of single and prolonged
      seizure in the developing brain. Using a heated-air FS paradigm, we subjected
      male rat pups to one, three, or nine episodes of brief FS on days 10 to 12
      postpartum. Neither hippocampal neuronal damage nor apoptosis was noted within 72
      hours after FS, nor was there significant hippocampal neuronal loss, aberrant
      mossy fiber sprouting, or altered seizure threshold to pentylenetetrazol in any
      FS group at adulthood. The adult rats subjected to nine episodes of early-life
      FS, however, showed long-term memory deficits as assessed by the Morris water
      maze. They also exhibited impaired intermediate and long-term memory but spared
      short-term memory in the inhibitory avoidance task. Three hours after inhibitory
      avoidance training, phosphorylation of cAMP response-element binding (CREB)
      protein in the hippocampus was significantly lower in nine-FS-group rats than in
      controls. Furthermore, rolipram administration, which activated the cAMP-CREB
      signaling pathway by inhibiting phosphodiesterase type IV, reversed the long-term
      memory deficits in nine-FS-group rats by enhancing hippocampal CREB
      phosphorylation. These results raise concerns about the long-term cognitive
      consequences of even brief frequently repetitive FS during early brain
      development.

PMID- 14681879
TI  - Long-term neuroplasticity and functional consequences of single versus recurrent
      early-life seizures.

PMID- 14681881
TI  - Infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1).
AB  - Autosomal recessive spinal muscular atrophy with respiratory distress type 1
      (SMARD1) is the second anterior horn cell disease in infants in which the genetic
      defect has been defined. SMARD1 results from mutations in the gene encoding the
      immunoglobulin micro-binding protein 2 (IGHMBP2) on chromosome 11q13. Our aim was
      to review the clinical features of 29 infants affected with SMARD1 and report on
      26 novel IGHMBP2 mutations. Intrauterine growth retardation, weak cry, and foot
      deformities were the earliest symptoms of SMARD1. Most patients presented at the
      age of 1 to 6 months with respiratory distress due to diaphragmatic paralysis and
      progressive muscle weakness with predominantly distal lower limb muscle
      involvement. Sensory and autonomic nerves are also affected. Because of the poor
      prognosis, there is a demand for prenatal diagnosis, and clear diagnostic
      criteria for infantile SMARD1 are needed. The diagnosis of SMARD1 should be
      considered in infants with non-5q spinal muscular atrophy, neuropathy, and muscle
      weakness and/or respiratory distress of unclear cause. Furthermore,
      consanguineous parents of a child with sudden infant death syndrome should be
      examined for IGHMBP2 mutations.

PMID- 14681882
TI  - Novel CACNA1A mutation causes febrile episodic ataxia with interictal cerebellar
      deficits.
AB  - Episodic ataxia type 2 (EA2) is a dominantly inherited disorder, characterized by
      spells of ataxia, dysarthria, vertigo, and migraines, associated with mutations
      in the neuronal calcium-channel gene CACNA1A. Ataxic spells lasting minutes to
      hours are provoked by stress, exercise, or alcohol. Some patients exhibit
      nystagmus between spells and some develop progressive ataxia later in life. At
      least 21 distinct CACNA1A mutations have been identified in EA2. The clinical and
      genetic complexities of EA2 have offered few insights into the underlying
      pathogenic mechanisms for this disorder. We identified a novel EA2 kindred in
      which members had ataxic spells induced by fevers or high environmental
      temperature. We identified a novel CACNA1A mutation (nucleotides 1253+1 G-->A)
      that was present in all subjects with febrile spells or ataxia. Moreover, we
      found that, regardless of age or interictal clinical status, all affected
      subjects had objective evidence of abnormal saccades, ocular fixation, and
      postural stability. These findings suggest that early cerebellar dysfunction in
      EA2 results from the intrinsically abnormal properties of the CACNA1A channel
      rather than a degenerative process.

PMID- 14681883
TI  - Magnetic resonance imaging shows delayed ischemic striatal neurodegeneration.
AB  - Brief focal ischemia leading to temporary neurological deficits induces delayed
      hyperintensity on T1-weighted magnetic resonance imaging (MRI) in the striatum of
      humans and rats. The T1 hyperintensity may stem from biochemical alterations
      including manganese (Mn) accumulation after ischemia. To clarify the significance
      of this MRI modification, we investigated the changes in the dorsolateral
      striatum of rats from 4 hours through 16 weeks after a 15-minute period of middle
      cerebral artery occlusion (MCAO), for MRI changes, Mn concentration, neuronal
      number, reactivities of astrocytes and microglia/macrophages, mitochondrial Mn
      superoxide dismutase (Mn-SOD), glutamine synthetase (GS), and amyloid precursor
      protein. The cognitive and behavioral studies were performed in patients and rats
      and compared with striatal T1 hyperintensity to show whether alteration in brain
      function correlated with MRI and histological changes. The T1-weighted MRI signal
      intensity of the dorsolateral striatum increased from 5 days to 4 weeks after 15
      minute MCAO, and subsequently decreased until 16 weeks. The Mn concentration of
      the dorsolateral striatum increased after ischemia in concert with induction of
      Mn-SOD and GS in reactive astrocytes. The neuronal survival ratio in the
      dorsolateral striatum decreased significantly from 4 hours through 16 weeks,
      accompanied by extracellular amyloid precursor protein accumulation and chronic
      glial/inflammatory responses. The patients and rats with neuroradiological
      striatal degeneration had late-onset cognitive and/or behavioral declines after
      brief focal ischemia. This study suggests that (1) the hyperintensity on T1
      weighted MRI after mild ischemia may involve tissue Mn accumulation accompanied
      by Mn-SOD and GS induction in reactive astrocytes, (2) the MRI changes correspond
      to striatal neurodegeneration with a chronic inflammatory response and signs of
      oxidative stress, and (3) the subjects with these MRI changes are at risk for
      showing a late impairment of brain function even though the transient ischemia is
      followed by total neurological recovery.

PMID- 14681884
TI  - Hereditary spastic paraparesis: disrupted intracellular transport associated with
      spastin mutation.
AB  - The commonest cause of hereditary spastic paraplegia (HSP) is mutation in the
      spastin gene. Both the normal function of spastin in the central nervous system
      and the mechanism by which mutation in spastin causes axonal degeneration are
      unknown. One hypothesis is that mutant spastin disrupts microtubule dynamics,
      causing an impairment of organelle transport on the microtubule network, which
      leads to degeneration in the distal parts of long axons. To study this neuronal
      and non-neuronal cells were transfected with either wild type or mutant spastin
      proteins. We demonstrated evidence of a transient interaction of wild-type
      spastin with microtubules, with resulting disassembly of microtubules, supporting
      a role for wild-type spastin as a microtubule-severing protein. Mutant spastin
      demonstrated an abnormal interaction with microtubules, colocalizing with but no
      longer severing microtubules. The abnormal interaction of mutant spastin with
      microtubules was demonstrated to be associated with an abnormal perinuclear
      clustering of mitochondria and peroxisomes, suggestive of an impairment of
      kinesin-mediated intracellular transport. Our findings indicate that an abnormal
      interaction of mutant spastin with microtubules, which disrupts organelle
      transport on the microtubule cytoskeleton, is likely to be the primary disease
      mechanism in HSP caused by missense mutations in the spastin gene.

PMID- 14681885
TI  - Ribonuclear inclusions in skeletal muscle in myotonic dystrophy types 1 and 2.
AB  - Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are caused by genomic expansions
      of CTG or CCTG repeats. When transcribed, these mutations give rise to repeat
      expansion RNAs that form nuclear inclusions and compromise the function of
      myonuclei. Here, we have used in situ hybridization and immunofluorescence to
      compare DM1 and DM2 and search for proteins that associate with the RNA nuclear
      (ribonuclear) inclusions. Although muscle disease is generally more severe in
      DM1, the ribonuclear inclusions were 8- to 13-fold more intense in DM2, implying
      greater amounts of repeat expansion RNA. Expression of repeat expansion RNA in
      myoblasts has been implicated in the pathogenesis of congenital DM1. However, we
      found that repeat expansion RNA is also expressed in myoblasts in DM2, a disorder
      that has not been associated with a congenital phenotype. Of 10 putative CUG
      binding proteins tested for colocalization with mutant RNA, only proteins in the
      muscleblind family were recruited into ribonuclear inclusions. Previous studies
      have shown activation of the protein kinase, PKR, by expanded CUG repeats in
      vitro. However, breeding experiments utilizing PKR knockout mice indicate that
      this kinase is not required for disease pathogenesis in a transgenic mouse model
      of DM1. We conclude that ribonuclear inclusions are a key feature of the muscle
      pathology in DM and that sequestration of muscleblind proteins may have a direct
      role in the disease process.

PMID- 14681888
TI  - Diagnostic value of electromyography and muscle biopsy in arthrogryposis
      multiplex congenita.
AB  - Arthrogryposis multiplex congenita (AMC), a clinical syndrome characterized by
      multiple congenital joint contractures, frequently is caused by lesions in the
      peripheral nervous system. Two standard tests for the evaluation of the motor
      unit are nerve conduction studies/electromyography (NCS/EMG) and muscle biopsy.
      We reviewed the diagnostic value of these two studies in the evaluation of AMC
      over a 23-year period, analyzing 38 patients with AMC who had NCS/EMG, muscle
      biopsy, or both. Final diagnoses were classified as neurogenic (8 patients),
      myopathic (10 patients), "other" (12 patients), or unknown (8 patients). Neither
      test alone had consistently high sensitivities, positive predictive values, or
      specificities. However, when NCS/EMG and muscle biopsy were concordant for
      neurogenic or myopathic findings, they were more accurate than either test alone,
      especially for neurogenic diseases. Test results were most commonly discordant in
      patients with "other" or unknown diagnoses. These findings suggest that when the
      clinical evaluation indicates a specific syndromic, developmental, or exogenous
      cause, NCS/EMG and muscle biopsy are not helpful and may not need to be
      performed. When the history, examination, and genetic evaluation are unrevealing,
      NCS/EMG and muscle biopsy together provide valuable diagnostic information.

PMID- 14681887
TI  - Amyloid beta protein toxicity mediated by the formation of amyloid-beta protein
      precursor complexes.
AB  - The amyloid-beta protein precursor, a type 1 transmembrane protein, gives rise to
      the amyloid beta-protein, a neurotoxic peptide postulated to be involved in the
      pathogenesis of Alzheimer's disease. Here, we show that soluble amyloid beta
      protein accelerates amyloid precursor protein complex formation, a process that
      contributes to neuronal cell death. The mechanism of cell death involves the
      recruitment of caspase-8 to the complex, followed by intracytoplasmic caspase
      cleavage of amyloid precursor protein. In vivo, the levels of soluble amyloid
      beta protein correlated with caspase-cleaved fragments of the amyloid precursor
      protein in brains of Alzheimer's disease subjects. These findings suggest that
      soluble amyloid beta protein-induced multimerization of the amyloid precursor
      protein may be another mechanism by which amyloid beta protein contributes to
      synapse loss and neuronal cell death seen in Alzheimer's disease.

PMID- 14681886
TI  - Insertion of mutant proteolipid protein results in missorting of myelin proteins.
AB  - Two brothers with a leukodystrophy, progressive spastic diplegia, and peripheral
      neuropathy were found to have proteinaceous aggregates in the peripheral nerve
      myelin sheath. The patients' mother had only subclinical peripheral neuropathy,
      but the maternal grandmother had adult-onset leukodystrophy. Sequencing of the
      proteolipid protein (PLP) gene showed a point mutation IVS4 + 1 G-->A within the
      donor splice site of intron 4. We identified one transcript with a deletion of
      exon 4 (Deltaex4, 169bp) encoding for PLP and DM20 proteins and lacking two
      transmembrane domains, and a second transcript with exon 4 + 10bp encoding three
      transmembrane domains. Immunohistochemistry showed abnormal aggregation in the
      myelin sheath of MBP and P0. Myelin-associated glycoprotein was present in the
      Schmidt-Lanterman clefts but significantly reduced in the periaxonal region.
      Using immunogold electron microscopy, we demonstrated the presence of mutated
      PLP/DM20 and the absence of the intact protein in the patient peripheral myelin
      sheath. We conclude that insertion of mutant PLP/DM20 with resulting aberrant
      distribution of other myelin proteins in peripheral nerve may constitute an
      important mechanism of dysmyelination in disorders associated with PLP mutations.

PMID- 14681889
TI  - A locus for complicated hereditary spastic paraplegia maps to chromosome 1q24
      q32.
AB  - We updated the clinical features of a consanguineous Arab Israeli family, in
      which four of seven children were affected by spastic paraplegia complicated by
      skin pigmentary abnormalities. A genomewide linkage screen performed for the
      family identified a new locus (SPG23) for this form of hereditary spastic
      paraplegia, in an approximately 25cM region of chromosome 1q24-q32, with a peak
      logarithm of odds score of 3.05.

PMID- 14681890
TI  - Myofibrillar myopathy caused by novel dominant negative alpha B-crystallin
      mutations.
AB  - We here report the second and third mutations in alphaB-crystallin causing
      myofibrillar myopathy. Two patients had adult-onset muscle weakness. Patient 1
      had cervical, limb girdle, and respiratory muscle weakness and died of
      respiratory failure. Patient 2 had proximal and distal leg muscle weakness. Both
      had myopathic electromyogram with abnormal electrical irritability and muscle
      biopsy findings of myofibrillar myopathy and mild denervation. Myofibrillar
      disintegration begins at the Z-disk and results in abnormal local expression of
      desmin, alphaB-crystallin, dystrophin, neural cell adhesion molecule (NCAM), and
      CDC2 kinase. Seven to 8% of nuclei display early apoptotic changes. Both patients
      carry a truncating mutation in the C-terminal region of alphaB-crystallin
      (464delCT in Patient 1 and Q151X in Patient 2) which is crucial for the
      solubilization and chaperone functions of the molecule. cDNA analysis shows the
      same mutations and no alternatively spliced transcripts. Immunoblots of muscle
      demonstrate increased expression of wild-type and reduced expression of the
      mutant protein. Immunoblots under nondenaturing conditions show that the mutant
      protein forms lower than normal molecular weight multimeric complexes with wild
      type. We conclude that (1) despite its reduced expression, the mutant protein
      exerts a dominant negative effect; (2) mutations in alphaB-crystallin are an
      infrequent cause of myofibrillar myopathy; (3) alphaB-crystallin-related
      myopathies display phenotypic heterogeneity.

PMID- 14681891
TI  - The release of tumor necrosis factor-alpha is associated with ischemic tolerance
      in human stroke.
AB  - Tumor necrosis factor (TNF)-alpha overexpression has been related to experimental
      ischemic tolerance when transient ischemia precedes cerebral infarction. We
      investigated TNF-alpha and interleukin (IL)-6 plasma concentrations in 283
      patients with an acute stroke within 24 hours after symptom onset. An ipsilateral
      transient ischemic attack (TIA) within 72 hours before stroke was recorded in 38
      patients. The infarct volume measured on computed tomography on days 4 to 7 and
      the frequency of poor outcome (Barthel Index score < 85) at 3 months were
      significantly lower in patients with prior TIA. Plasma concentrations of TNF
      alpha were higher (42.5 +/- 9.9 vs 13.1 +/- 6.4pg/ml, p < 0.0001) and IL-6 levels
      were lower (10.1 +/- 6.2 vs 28.3 +/- 17.3pg/ml, p < 0.0001) in patients with
      prior TIA. A new variable termed TNF-alpha/IL-6 index was considered positive
      when TNF-alpha was greater than 30pg/ml and IL-6 was less than 30pg/ml. Positive
      TNF-alpha/IL-6 index was found in 92% of patients with prior TIA and in 1% of
      those without. TNF-alpha/IL-6 index (p = 0.0003) and TIA (p = 0.0001) were
      associated with good outcome in logistic regression analysis after adjusting for
      potential confounding factors. Ischemic tolerance in acute stroke is associated
      with increased plasma levels of TNF-alpha in the presence of reduced
      concentrations of IL-6.

PMID- 14681892
TI  - The expanding mutational spectrum of MERRF substitution G8361A in the
      mitochondrial tRNALys gene.
AB  - In a case of childhood-onset myoclonus epilepsy with "ragged-red fibers" (MERRF),
      a hitherto unreported mutation within the mitochondrial tRNA(Lys) gene was
      identified as the cause of the disease. Substitution G8361A was maternally
      inherited, heteroplasmic in all tissues tested, and correlated with mitochondrial
      dysfunction in individual muscle fibers. The growing number of MERRF-associated
      mutations within the tRNA(Lys) gene affirms the specific role of this
      mitochondrial tRNA in the pathogenesis of the disease.

PMID- 14681894
TI  - Chlamydia pneumoniae and the risk for exacerbation in multiple sclerosis
      patients.
AB  - In this prospective study of 73 relapsing remitting multiple sclerosis patients
      followed up for a mean of 1.7 years, the relation was tested between
      serologically defined Chlamydia pneumoniae (CP) infection periods and
      exacerbation rate. Episodes of serologically defined CP infections were observed
      in a subgroup, and these episodes were associated with increased risk for
      exacerbation. CP polymerase chain reaction was positive in most of the CP
      seropositive patients. No correlation was found between the anti-CP antibody
      increase and titers of control antibodies.

PMID- 14681893
TI  - Pathogenesis of clinical signs in recessive ataxia with saccadic intrusions.
AB  - We describe a family of Slovenian descent with progressive ataxia, corticospinal
      signs, axonal sensorimotor neuropathy, and disruption of visual fixation by
      saccadic intrusions. Chromosome mapping indicated a mutation on 1p36, and this
      recessive disorder has been designated spinocerebellar ataxia with saccadic
      intrusions. Affected patients showed overshooting horizontal saccades,
      macrosaccadic oscillations, and increased velocity of larger saccades; other eye
      movements were normal. Slowed conduction in axons that are selectively vulnerable
      to the molecular defect could explain both the sensorimotor neuropathy and the
      saccadic disorder, which would be caused by delayed feedback control because of
      slow conduction in cerebellar parallel fibers.

PMID- 14681895
TI  - Atypical dementia associated with a novel presenilin-2 mutation.
AB  - We describe an Italian pedigree with hereditary dementia associated with a novel
      T122R mutation in the presenilin-2 gene (PSEN2). The clinical history, symptom
      presentation, and structural neuroimaging were consistent with an atypical form
      of dementia. Disease expression varied within family members. One in a pair of
      mutated monozygotic twins had evident signs of disease, whereas the other did
      not, even if her functional neuroimaging investigations, cerebrospinal fluid
      levels of Abeta1-42, and Tau protein were able to provide markers for future
      disease development. These observations suggest the importance of still unknown
      biological and perhaps environmental factors in the disease determination.

PMID- 14681896
TI  - Vascular parkinsonism in moyamoya: microvascular biopsy and imaging correlates.
AB  - We highlight the first case to our knowledge of vascular parkinsonism with
      angiographic moyamoya and functional imaging correlates. In addition,
      transmission electron microscopy of the cutaneous vasculature revealed the mean
      smooth muscle cell layer of the terminal arterioles to be significantly higher
      compared with ischemic stroke patients classified by vascular risk factors.
      Smooth muscle cell thickness was also greater in those with small vessel and
      large vessel strokes compared with cardioembolic strokes. The marked cutaneous
      arteriolar smooth muscle cell hypertrophy may be a useful surrogate marker for
      those at risk of developing angiographic moyamoya.

PMID- 14681897
TI  - Minocycline is protective in a mouse model of Huntington's disease.

PMID- 14681898
TI  - Minocycline is not beneficial in a phenotypic mouse model of Huntington's
      disease.

PMID- 14681905
TI  - An indirect test of the new mutation hypothesis associating advanced paternal age
      with the etiology of schizophrenia.
AB  - Two studies by Malaspina et al. [2001: Arch Gen Psychiatr 58:361-367]; [2002: Am
      J Med Genet 114:299-303] have put forward the hypothesis that advanced paternal
      age with concomitant mutations in the male germ line is associated with sporadic
      schizophrenia in offspring. The hypothesis was supported by an observation of a
      monotonic increase in the risk for schizophrenia with increased paternal age, and
      a second observation in a separate sample of greater paternal mean age at birth
      among cases of apparent sporadic schizophrenia. The present study did not test
      the association of the risk of schizophrenia with advanced paternal age, but
      repeated the test of paternal age at birth among sporadic versus familial
      schizophrenic probands. We also examined the risk of schizophrenia, psychosis,
      and broad psychosis among paternal 1st and 2nd degree relatives of schizophrenic
      probands as a function of paternal age at birth of the proband, reasoning that if
      probands born to older fathers are more likely to be sporadic cases, the risk of
      schizophrenia (or psychosis) should be lower on the paternal side of the family.
      Results indicate a lack of support for the previous finding that sporadic
      probands tend to have older fathers at birth than familial probands. Results also
      failed to support the related hypothesis that increased paternal age is
      associated with the lower risk of schizophrenia (or psychosis) in the relatives
      of schizophrenic probands. The failure to support the paternal age hypothesis may
      be a function of heterogeneous samples, but calls for further research in the
      context of family studies.

PMID- 14681904
TI  - Role of dopamine D3 receptor (DRD3) and dopamine transporter (DAT) polymorphism
      in cognitive dysfunctions and therapeutic response to atypical antipsychotics in
      patients with schizophrenia.
AB  - Molecular components of the dopaminergic system may play an important role in the
      pathophysiology of schizophrenia. In this study, we investigated the relationship
      of the Ser9Gly (S/G) polymorphism of the dopamine D3 receptor (DRD3) and the
      variable number of tandem repeats (VNTR) polymorphism of the dopamine transporter
      (DAT) with therapeutic response to atypical antipsychotics (clozapine,
      olanzapine, quetiapine, risperidone) and cognitive functions. No associations
      were found between the DRD3 and DAT polymorphisms and schizophrenia. The S/S
      genotype and the S allele were more frequent in the non-responder patients (n =
      28) than in the group of responders (n = 47) (cut-off: >20-point improvement in
      Global Assessment of Functioning (GAF) scale). The patients with S/S genotype
      completed fewer categories and had more perseverative errors in the Wisconsin
      Card Sorting Test (WCST) compared with the S/G patients. The S/S and S/G patients
      did not differ in positive and negative symptoms, GAF scores, WCST failure to
      maintain set, and verbal learning. No differences in symptoms or WCST measures
      were observed in the patients with different DAT genotypes. These results suggest
      that the S/S genotype of the DRD3 is associated with worse therapeutic response
      and more severe executive dysfunctions in patients with schizophrenia.

PMID- 14681906
TI  - Interleukin-1beta (IL-1beta) gene and increased risk for the depressive symptom
      dimension in schizophrenia spectrum disorders.
AB  - Interleukin-1beta (IL-1beta), as well as other cytokines, has been classically
      implicated in the pathophysiology of major psychiatric disorders such as
      schizophrenia and major depression, and recent studies have implicated the IL
      1beta gene and schizophrenia. Nevertheless, new approaches to this complex
      phenotype are necessary to clarify the risk conferred by this gene, either to the
      disorder or to its clinical manifestations. The aim of the present study was to
      explore the effect of a genetic polymorphism of the promoter region of the IL
      1beta gene, in schizophrenia defined with: (i) a categorical diagnosis and (ii) a
      multidimensional symptom approach. We studied 356 individuals from 89 nuclear
      families consisting of one affected individual and the unaffected father, mother,
      and sib, in a family-based association study design. We find a trend for biased
      transmission of allele 2 from heterozygous parents to affected offspring,
      categorically defined (P = 0.07). This tendency was not observed in the healthy
      offspring. Using a multidimensional symptom approach to the diagnosis, the
      association was confirmed in psychotic patients showing the depressive symptom
      dimension (P = 0.02).

PMID- 14681907
TI  - Novel CAG/CTG repeat expansion mutations do not contribute to the genetic risk
      for most cases of bipolar disorder or schizophrenia.
AB  - The possible presence of anticipation in bipolar affective disorder and
      schizophrenia has led to the hypothesis that repeat expansion mutations could
      contribute to the genetic etiology of these diseases. Using the repeat expansion
      detection (RED) assay, we have systematically examined genomic DNA from 100
      unrelated probands with schizophrenia and 68 unrelated probands with bipolar
      affective disorder for the presence of CAG/CTG repeat expansions. Our results
      show that 28% of the probands with schizophrenia and 30% of probands with bipolar
      disorder have a CAG/CTG repeat in the expanded range, but that each expansion
      could be explained by one of three nonpathogenic repeat expansions known to exist
      in the general population. We conclude that novel CAG/CTG repeat expansions are
      not a common genetic risk factor for bipolar disorder or schizophrenia.

PMID- 14681908
TI  - Phenotypic characterization and genealogical tracing in an Afrikaner
      schizophrenia database.
AB  - Founder populations hold tremendous promise for mapping genes for complex traits,
      as they offer less genetic and environmental heterogeneity and greater potential
      for genealogical research. Not all founder populations are equally valuable,
      however. The Afrikaner population meets several criteria that make it an ideal
      population for mapping complex traits, including founding by a small number of
      initial founders that likely allowed for a relatively restricted set of mutations
      and a large current population size that allows identification of a sufficient
      number of cases. Here, we examine the potential to conduct genealogical research
      in this population and present initial results indicating that accurate
      genealogical tracing for up to 17 generations is feasible. We also examine the
      clinical similarities of schizophrenia cases diagnosed in South Africa and those
      diagnosed in other, heterogeneous populations, specifically the US. We find that,
      with regard to basic sample descriptors and cardinal symptoms of disease, the two
      populations are equivalent. It is, therefore, likely that results from our
      genetic study of schizophrenia will be applicable to other populations. Based on
      the results presented here, the history and current size of the population, as
      well as our previous analysis addressing the extent of background linkage
      disequilibrium (LD) in the Afrikaners, we conclude that the Afrikaner population
      is likely an appropriate founder population to map genes for schizophrenia using
      both linkage and LD approaches.

PMID- 14681909
TI  - Variation in the urokinase-plasminogen activator gene does not explain the
      chromosome 10 linkage signal for late onset AD.
AB  - Linkage studies indicate that the same region of chromosome 10 contains a risk
      locus for late onset Alzheimer disease (LOAD) and a QTL for plasma Abeta42 levels
      suggesting that a single locus may influence risk for AD by elevating plasma
      Abeta42 [Ertekin-Taner et al., 2000; Myers et al., 2000]. A strong positional and
      biological candidate is the urokinase-plasminogen activator (PLAU) gene. Eight
      polymorphisms spanning the entire gene were examined using case control (CC) and
      family-based association methods. No association was observed by any method
      making it unlikely that variation in PLAU explains our linkage data.

PMID- 14681910
TI  - No evidence of linkage or association between the norepinephrine transporter
      (NET) gene MnlI polymorphism and adult ADHD.
AB  - Attention deficit hyperactivity disorder (ADHD) is a prevalent psychiatric
      condition in children and follow-up studies have indicated that one to two thirds
      of patients continue to suffer from ADHD during late adolescence and adulthood.
      The mechanism of action of the new selective noradrenergic reuptake inhibitor,
      atomoxetine, efficacious in the treatment of ADHD symptoms, suggests that the
      norepinephrine transporter (NET) may be involved in ADHD. The aim of this study
      was to investigate for the presence of linkage disequilibrium between the MnlI
      RFLP in the NET gene and adult ADHD in a sample of nuclear families. The MnlI
      polymorphism was typed in 128 trios and analyzed using the transmission
      disequilibrium test (TDT). There was no preferential transmission of either
      allele (chi(2) = 0.209, df = 1, P = 0.647).

PMID- 14681911
TI  - Co-occurrence of ADHD and low IQ has genetic origins.
AB  - Previous studies show that the symptoms of attention deficit hyperactivity
      disorder (ADHD) and lower intelligence quotient (IQ) covary in children. We
      investigated the aetiology of this association in a large population-based sample
      of 5-year-old twins. The twins were individually assessed on an IQ test, and data
      on ADHD symptoms were obtained from mother interviews and teacher ratings.
      Confirming previous studies, the phenotypic correlation between ADHD symptom
      scores and IQ was -0.3 and, in a categorical analysis, children with a Diagnostic
      and Statistical Manual of Mental Disorders (DSM-IV) ADHD research diagnosis
      obtained IQ scores nine points lower, on average, than comparison children. We
      show here that the co-occurrence of ADHD and lower IQ has genetic origins: 86% of
      the association between ADHD symptom scores and IQ, and 100% of the association
      between ADHD diagnosis and IQ, was accounted for by genetic influences that are
      shared by ADHD and IQ. Some candidate genes for ADHD could also contribute to
      variation in IQ or vice versa.

PMID- 14681912
TI  - Dinucleotide repeat polymorphism in interferon-gamma gene is not associated with
      sporadic Alzheimer's disease.
AB  - Various factors have been suggested to participate in Alzheimer's disease (AD)
      pathology, and some inflammatory cytokines may play an important role in the
      development of AD. Interferon-gamma (IFNG), an important pro-inflammatory
      cytokine, is encoded by a single gene mapped to chromosome 12, one of the
      candidate locus of AD. The first intron in the IFNG gene represents a CA repeat
      polymorphism that is possible to affect the IFNG secretion dose. We speculate
      that the polymorphism may have some roles on the inflammatory process and the
      pathologic change in AD, so we analyzed the IFNG gene polymorphism in 199
      Japanese AD patients and 225 Japanese controls. There were no significant
      differences in allele frequency between the AD and control groups. We conclude
      that IFNG gene polymorphism is not associated with development of AD.

PMID- 14681913
TI  - Association between interleukin 1-beta promoter (-511) polymorphism and
      depressive symptoms in Alzheimer's disease.
AB  - Depressive symptoms have been associated with raised interleukin 1-beta (IL
      1beta) plasma levels. The presence of behavioral and psychological symptoms of
      dementia (BPSD) in Alzheimer's disease, including depressive symptoms, have been
      shown to be influenced by common genetic polymorphisms. A common polymorphism in
      the promoter region of IL-1beta has been linked to altered synthesis of IL-1beta.
      We hypothesize that this common genetic polymorphism is a risk factor for the
      appearance of depressive symptoms in AD. A total of 133 subjects, diagnosed as
      probable AD and 156 controls were genotyped for the -511 variant of IL-1beta.
      Neither genotype or allele frequencies differed between the AD and control group.
      However, an allelic association was found between the T variant and the symptoms
      of depression in AD subjects. Genotypic analysis showed that heterozygotes were
      three times more likely to develop depressive symptoms than CC homozygotes.

PMID- 14681914
TI  - The 1239G/C polymorphism in exon 5 of BACE1 gene may be associated with sporadic
      Alzheimer's disease in Chinese Hans.
AB  - Beta-site amyloid-precursor protein cleaving enzyme (BACE1) is a candidate risk
      factor for Alzheimer's disease (AD) because of involving in generating beta
      amyloid peptide, which is thought to play a central role in the pathogenesis of
      the disease. A single nucleotide polymorphism 1239G/C in exon 5 of BACE1 gene and
      a weak association between this polymorphism and AD in Caucasian APOEepsilon4
      allele carriers has been reported. To examine possible association of the
      polymorphism with sporadic AD, two Chinese Han cohorts including 257 patients and
      242 age-matched controls in Guangzhou and 112 patients and 113 controls in
      Chengdu were genotyped using PCR-RFLP techniques. The frequency of the C allele
      in controls of both cohorts was 0.65, which was higher than that in Caucasian
      populations [0.39 by Nowotny et al. 2001: Neuroport 12:1799-1802; 0.44 by
      Nicolaou et al. 2001: Neurogenetics 3:203-206]. There was a significant excess of
      C allele among the patients in both cohorts (Guangzhou, 0.71 vs. 0.65, chi(2) =
      5.20, P = 0.02; Chengdu, 0.74 vs. 0.65, chi(2) = 4.36, P = 0.04). The CC genotype
      was found to be associated with AD (Guangzhou cohort, OR = 1.56, 95% CI = 1.09
      2.23; Chengdu cohort, OR = 1.74, 95% CI = 1.03-2.95; combined sample: OR = 1.61,
      95% CI = 1.20-2.17). The association remained in non-APOE epsilon4 allele
      carriers when all subjects were divided on the basis of the APOEepsilon4 status.
      Our findings suggest that the 1239G/C polymorphism in exon 5 of BACE1 gene may be
      associated with sporadic AD in Chinese Hans.

PMID- 14681915
TI  - Personality traits in young female apolipoprotein E (apoE) epsilon4 and non
      epsilon4 carriers.
AB  - Apolipoprotein E (apoE) is the major brain apolipoprotein, and is related to the
      functional integrity of the central nervous system. It has been reported that the
      apoE genetic polymorphism is associated with several components of childhood and
      adolescent temperament. To study the effect of the presence of the apoE epsilon4
      allele on adult personality factors, tridimensional personality questionnaire
      (TPQ) scores were compared for epsilon4 and non-epsilon4 carriers in a sample
      population consisting of 135 young females. No significant differences were
      demonstrated comparing the scores for the two groups. Our findings suggest that
      the investigated apoE polymorphism does not play a major role in personality
      trait factors, as assessed by TPQ.

PMID- 14681916
TI  - Association between brain-derived neurotrophic factor 196 G/A polymorphism and
      personality traits in healthy subjects.
AB  - Several lines of evidence suggest that a certain type of personality or
      temperament is at risk for developing neuropsychiatric diseases, and that brain
      derived neurotrophic factor (BDNF) might be involved in pathophysiology of
      neuropsychiatric diseases such as mood disorders. Considering the role of BDNF
      and personality traits in the neuropsychiatric diseases, it is of interest to
      examine the association between BDNF gene polymorphism and personality test
      scores. In this study, we examined the association between 196 G/A the
      polymorphism in the coding region of the BDNF gene and personality traits scores
      (temperament and character inventory (TCI) and NEO personality inventory (NEO
      PI)) in Japanese healthy subjects. We found that female, but not male, subjects
      with BDNF genotype A/A have high scores in reward dependence on TCI and high
      scores in extraversion on NEO-PI as compared with other genotypes (G/A or G/G),
      suggesting an association between reward dependence (or extraversion) personality
      traits and BDNF genotype in female subjects. Our findings suggest that BDNF 196
      A/G polymorphism might be associated with personality traits in female, but not
      male, healthy subjects.

PMID- 14681917
TI  - No association between allelic variants of HOXA1/HOXB1 and autism.
AB  - Two recent studies have reported conflicting findings of association of a variant
      in the HOXA1 gene and autism. To try to resolve the conflict in findings, we
      conducted an association study in 78 Irish families of the reported DNA variants.
      We did not find statistically significant association between the variants and
      autism. Similarly there was no evidence of preferential transmission of variants
      from parent of either sex to affected offspring. We also report negative findings
      for HOXB1 variants. We conclude that the HOXA1/B1 are unlikely to be the
      susceptibility genes for autism in our sample.

PMID- 14681919
TI  - No association between a neuronal nitric oxide synthase (NOS1) gene polymorphism
      on chromosome 12q24 and bipolar disorder.

PMID- 14681918
TI  - Combined family trio and case-control analysis of the COMT Val158Met polymorphism
      in European patients with anorexia nervosa.
AB  - The high activity Val158 (H) allele of the dopamine-metabolizing enzyme catechol
      O-methyltransferase (COMT) was associated with anorexia nervosa (AN) in a recent
      family trio-based study of patients from Israel. In an attempt to replicate this
      finding, we performed a combined family trio and case-control study in an
      European population from seven centers in six different countries (Austria,
      Germany, Great Britain, Italy [Milan], Italy [Florence], Slovenia, and Spain),
      together contributing a total of 372 family trios, 684 controls and 266 cases.
      TDT analyses of high (H) and low (L) alleles in family trios showed that H allele
      and L allele were each transmitted 101 times (chi(2) = 0, ns). Allele-wise case
      control analysis using separate samples simply combined from the centers was also
      not significant, with the frequencies of the H allele 50% in cases and same in
      controls. Stratified analysis of data from all centers gave an odds ratio of 0.98
      (Cornfield 95% confidence limits 0.78-1.24). Analysis by genotype was likewise
      not significant (overall chi(2) = 0.42). Because we were not able to support the
      primary hypothesis that Val158Met is a risk factor for AN, we did not perform
      secondary analysis of minimum body mass index (mBMI), age at onset or illness
      subtype (restricting or binge purging anorexia). Overall we found no support for
      the hypothesis that the Val158 allele of COMT gene is associated with AN in our
      combined European sample.

PMID- 14681920
TI  - Linkage disequilibrium analysis of polymorphisms in the gene for myelin
      oligodendrocyte glycoprotein in Tourette's syndrome patients from a Chinese
      sample.
AB  - Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterised
      by multiple motor and phonic tics, which wax and wane. Recently, evidence has
      accumulated supporting the role of autoimmune mechanisms in the aetiology of GTS,
      suggesting that it is within the paediatric autoimmune neuropsychiatric disorders
      associated with streptococcal infection (PANDAS) spectrum of childhood
      neurobehavioural disorders. An immunopathogenic role of antibodies against myelin
      oligodendrocyte glycoprotein (MOG) has been suggested in this syndrome. In this
      study, we investigate the association of three microsatellite polymorphisms
      (MOGa, MOGb, MOGc) in the gene for MOG with GTS in 197 family trios collected
      from southwest China. Linkage disequilibrium between these three markers was
      observed with the strongest between MOGa and MOGc (D' = 0.541, P = 0.000). We did
      not find overall significant evidence for distorted transmission of any of these
      three markers of MOG gene in GTS, although we observed a weak preferential
      transmission of the 148 bp allele of MOGc (chi(2) = 4.000, P = 0.046) which did
      not survive correction for multiple testing. Our results suggest that there is no
      association between the MOG gene polymorphisms we tested and GTS.

PMID- 14681922
TI  - Association between the TPH gene A218C polymorphism and suicidal behavior: a meta
      analysis.
AB  - Genes encoding proteins involved in serotonergic metabolism are major candidates
      in association studies of suicidal behavior. The tryptophan hydroxylase (TPH)
      gene, which codes for the rate-limiting enzyme of serotonin biosynthesis, is a
      major candidate gene and has been extensively studied in association studies of
      suicidal behavior, providing conflicting results. It is difficult to interpret
      these conflicting results due to lack of power, ethnic heterogeneity, and
      variations in the sampling strategies (in particular for controls) and in the
      polymorphism of the TPH gene studied. Meta-analyses can improve the statistical
      power for the analysis of the effects of candidate vulnerability factors. The
      analysis of the sources of heterogeneity that contribute to these conflicting
      results is an important step in the interpretation of these conflicting
      association results and in the interpretation of the results of a meta-analysis.
      We selected all of the published association studies between the TPH gene
      polymorphism and suicidal behavior. Nine association studies between the A218C
      TPH polymorphism and suicidal behavior fulfilled the inclusion criteria. A
      significant association was observed between the A218C polymorphism and suicidal
      behavior using the fixed effect method (odds ratio (OR) = 1.62; 95% confidence
      interval (CI) = [1.26; 2.07]) and the random effect method (OR = 1.61; 95% CI =
      [1.11; 2.35]). The analysis of the sources of heterogeneity showed that two
      studies (one positive and one negative) significantly deviated from the
      calculated global effect. The meta-analysis performed after removing those two
      studies also revealed a significant association between the TPH A218C
      polymorphism and suicidal behavior. Both analyses suggested that the A allele has
      a dose-dependent effect on the risk of suicidal behavior.

PMID- 14681921
TI  - Mutation screen of the glutamate decarboxylase-67 gene and haplotype association
      to unipolar depression.
AB  - Abnormally low concentrations of brain gamma-aminobutyric acid (GABA) have been
      reported in unipolar depression. Almost all of the brain GABA is synthesized by
      glutamate decarboxylase (GAD) enzymes (GAD67 and GAD65). These enzymes,
      therefore, play a central role in brain GABA homeostasis. We screened all the 17
      exons of the GAD67 gene for mutations using single strand conformation
      polymorphism (SSCP) or denaturing high pressure liquid chromatography (dHPLC) in
      a sample of 43 individuals diagnosed with major unipolar depression or other
      disorders with putative GABAergic dysfunction. We identified eight novel variants
      (five synonymous base substitutions, two insertion/deletions and one tandem
      repeat). Three relatively common (minor allele frequency >20%) single nucleotide
      polymorphisms (SNPs), located in the 5' non-coding region (exon 0), intron 8, and
      the 3' non-coding region (exon 16) of the gene, were genotyped in 103 European
      American (EA) subjects with depression and 125 EA psychiatrically screened
      controls. Linkage disequilibrium (LD) and haplotype frequencies were estimated
      using the 3LOCUS program. Significant LD was observed between the intron 8 SNP
      and the exon 16 SNP and between the exon 0 SNP and the exon 16 SNP. Three common
      GAD67 haplotypes were observed in this population, which accounted for >90% of
      the possible GAD67 three-locus haplotypes. Comparison of SNP and haplotype
      frequencies between individuals with depression and controls revealed no
      differences. These results demonstrate a significant within-gene LD for GAD67 in
      the EA population and begin to establish a haplotype map for this gene.
      Furthermore, these results suggest that common genetic variation within the GAD67
      gene does not play a major role in the predisposition to unipolar depression.

PMID- 14681923
TI  - Re-screening serotonin receptors for genetic variants identifies population and
      molecular genetic complexity.
AB  - We have re-screened the genes for the 5-HT1A, 5-HT2A, 5-HT2C, and 5-HT7 serotonin
      receptors for genetic variants in a large African-American and Caucasian-American
      population sample. We have identified eight novel variants in these genes
      including four that are predicted to cause amino acid substitutions. These
      variants are additional candidates for association studies of behavioral
      disorders such as depression and schizophrenia as well as quantitative
      personality traits. We have also detected some, but not all, previously
      identified variants in these genes suggesting that many previously identified
      variants are unique to specific populations. The results of this study, and
      previous screens of serotonin receptors, demonstrate that the genes for serotonin
      receptors display marked population and molecular genetic complexity. These
      levels of complexity may have a substantial effect on genetic association studies
      of human behavioral variability related to these genes. We discuss the
      implications of these findings and propose methods to address complexity in
      genetic association studies.

PMID- 14681924
TI  - Ethnicity-independent genetic basis of functional psychoses: a genotype-to
      phenotype approach.
AB  - The functional psychoses schizophrenia, schizoaffective disorder, and bipolar
      illness represent complex clinical syndromes that are characterized by phenotypic
      heterogeneity. Yet evidence from numerous studies suggests that (1) the
      prevalence of schizophrenia and bipolar illness is with 1% very similar across
      ethnicities, and (2) a strong genetic component is involved in the disorders'
      pathogenesis. Using data from different US-American ethnicities (77 families with
      a total of 17 unaffected and 170 affected sib pairs; 276 marker loci), we
      searched for ethnicity-independent oligogenic susceptibility loci for which the
      between-sib genetic similarity in affected sib pairs deviated from the expected
      values. Specifically, we addressed the question of the extent to which genetic
      risk factors and their interactions constitute multigenic inheritance of
      functional psychoses across populations and might constitute universal targets
      for treatment. Our novel multivariate genotype-to-phenotype search strategy was
      based on a genetic similarity function that allowed us to quantify the inter
      individual genetic distances d(x(i), x(j)) between the allelic genotype patterns
      x(i), x(j) of any two subjects i, j with respect to n loci l(1), l(2), em leader
      l(n). Thus, we were able to assess the between-ethnicity, the within-ethnicity,
      and the within-family genetic similarities. The problem of ethnicity-independent
      vulnerability was addressed by treating the Afro-American families as "training"
      samples, while the non-Afro-American families served as independent "test"
      samples. We evaluated the between-sib similarities, which were expected to
      deviate from "0.5" in affected sib pairs if the region of interest contained
      markers close to vulnerability genes. The reference value "0.5" was derived from
      the parent-offspring similarities that are always 0.5, irrespective of the
      affection status of parents and offspring. We found 12 vulnerability loci on
      chromosomes 1, 4, 5, 6, 13, 14, 18, and 20, that were reproducible across the two
      samples under comparison and therefore, likely to constitute an ethnicity
      independent, oligogenic vulnerability model of functional psychoses. The elevated
      vulnerability appeared to be unspecific and to act in such a way that exogenous
      factors become more likely to trigger the onset of psychiatric illnesses.

PMID- 14681925
TI  - Effects of dopamine receptor D4 variation on alcohol and tobacco use and on
      novelty seeking: multivariate linkage and association analysis.
AB  - The dopamine D4 receptor gene contains a polymorphic sequence consisting of a
      variable number of 48-base-pair (bp) repeats, and there have been a number of
      reports that this polymorphism is associated with variation in novelty seeking or
      in substance abuse and addictive behaviors. In this study we have assessed the
      linkage and association of DRD4 genotype with novelty seeking, alcohol use, and
      smoking in a sample of 377 dizygotic twin pairs and 15 single twins recruited
      from the Australian Twin Registry (ATR). We found no evidence of linkage or
      association of the DRD4 locus with any of the phenotypes. We made use of repeated
      measures for some phenotypes to increase power by multivariate genetic analysis,
      but allelic effects were still non-significant. Specifically, it has been
      suggested that the DRD4 7-repeat allele is associated with increased novelty
      seeking in males but we found no evidence for this, despite considerable power to
      do so. We conclude that DRD4 variation does not have an effect on use of alcohol
      and the problems that arise from it, on smoking, or on novelty seeking behavior.

PMID- 14681926
TI  - Nature and nurture: interaction and coaction.
AB  - The sophistry of the "Nature versus Nurture" formulation is becoming ever more
      apparent as a consequence of the rapid advances in understanding of the basic
      mechanisms of heredity and in the application of this knowledge to a wide
      spectrum of issues of human health and welfare. It is clear that a more accurate
      formulation would emphasize the interaction and coaction of genetic and
      environmental factors in their influence on complex phenotypes. Furthermore, the
      potential dependence of the influence of a particular gene on other genes in the
      system is increasingly realized. This paper documents these perspectives by
      examples of gene-environment interaction and gene-gene interaction both from
      animal model and from human research that reveal both the potential power and
      subtlety of these interactive effects.

PMID- 14681927
TI  - Morphologic characterization of rat taste receptor cells that express components
      of the phospholipase C signaling pathway.
AB  - Rat taste buds contain three morphologically distinct cell types that are
      candidates for taste transduction. The physiologic roles of these cells are,
      however, not clear. Inositol 1,4,5-triphosphate (IP(3)) has been implicated as an
      important second messenger in bitter, sweet, and umami taste transductions.
      Previously, we identified the type III IP(3) receptor (IP(3)R3) as the dominant
      isoform in taste receptor cells. In addition, a recent study showed that
      phospholipase Cbeta(2) (PLCbeta(2)) is essential for the transduction of bitter,
      sweet, and umami stimuli. IP(3)R3 and PLCbeta(2) are expressed in the same subset
      of cells. To identify the taste cell types that express proteins involved in PLC
      signal transduction, we used 3,3'diaminobenzidine tetrahydrochloride
      immunoelectron microscopy and fluorescence microscopy to identify cells with
      IP(3)R3. Confocal microscopy was used to compare IP(3)R3 or PLCbeta(2)
      immunoreactivity with that of some known cell type markers such as serotonin,
      protein gene-regulated product 9.5, and neural cell adhesion molecule. Here we
      show that a large subset of type II cells and a small subset of type III cells
      display IP(3)R3 immunoreactivity within their cytoplasm. These data suggest that
      type II cells are the principal transducers of bitter, sweet, and umami taste
      transduction. However, we did not observe synapses between type II taste cells
      and nerve fibers. Interestingly, we observed subsurface cisternae of smooth
      endoplasmic reticulum at the close appositions between the plasma membrane of
      type II taste cells and nerve processes. We speculate that some type II cells may
      communicate to the nervous system via subsurface cisternae of smooth endoplasmic
      reticulum in lieu of conventional synapses.

PMID- 14681928
TI  - Neuronal and astrocyte expression of nicotinic receptor subunit beta4 in the
      adult mouse brain.
AB  - Neuronal nicotinic acetylcholine receptor (nAChR) expression and function are
      customized in different brain regions through assembling receptors from closely
      related but genetically distinct subunits. Immunohistochemical analysis of one of
      these subunits, nAChRbeta4, in the mouse brain suggests an extensive and
      potentially diverse role for this subunit in both excitatory and inhibitory
      neurotransmission. Prominent immunostaining included: 1) the medial habenula,
      efferents composing the fasciculus retroflexus, and the interpeduncular nucleus;
      2) nuclei and ascending tracts of the auditory system inclusive of the medial
      geniculate; 3) the sensory cortex barrel field and cell bodies of the ventral
      thalamic nucleus; 4) olfactory-associated structures and the piriform cortex; and
      5) sensory and motor trigeminal nuclei. In the hippocampus, nAChRbeta4 staining
      was limited to dendrites and soma of a subset of glutamic acid dehydrogenase
      positive neurons. In C57BL/6 mice, but to a lesser extent in C3H/J, CBA/J, or CF1
      mice, a subpopulation of astrocytes in the hippocampal CA1 region prominently
      expressed nAChRbeta4 (and nAChRalpha4). Collectively, these results suggest that
      the unique functional and pharmacological properties exerted by nAChRbeta4 on
      nAChR function could modify and specialize the development of strain-specific
      sensory and hippocampal-related characteristics of nicotine sensitivity including
      the development of tolerance.

PMID- 14681929
TI  - Mouse strain-specific nicotinic acetylcholine receptor expression by inhibitory
      interneurons and astrocytes in the dorsal hippocampus.
AB  - The response by individuals to nicotine is likely to reflect the interaction of
      this compound with target nAChRs. However, resolving how different genetic
      backgrounds contribute to unique mouse strain-specific responses to this compound
      remains an important and unresolved issue. To examine this question in detail,
      expression of the nicotine acetylcholine receptor (nAChR) subunits alpha3,
      alpha4, alpha5, alpha7, beta2, and beta4 was measured in the dorsal hippocampus
      using immunohistochemistry in mouse strains or lines BALB/c, C3H/J, C57BL/6,
      CBA/J, DBA/2, Long Sleep (LS), Short Sleep (SS), and CF1. The nAChRs in all mice
      colocalized with glutamic acid decarboxylase (GAD)-positive interneurons that
      were subclassified into at least four groups based on nAChR subunit
      heterogeneity. A notable difference between mouse strains was the expression of
      nAChRs by astrocyte subpopulations in CA1 subregions whose numbers vary inversely
      with nAChR-immunostained neurons. This novel relationship also correlated with
      published parameters of strain sensitivity to nicotine. Attempts to identify the
      origin of this significant difference in nAChR expression among strains included
      comparison of the entire nAChRalpha4 gene sequence. Although multiple
      polymorphisms were identified, including two that changed nAChRalpha4 amino acid
      coding, none of these clearly correlate with strain-related differences in cell
      type-specific nAChR expression. These findings suggest that mouse strain-specific
      behavioral and physiological responses to nicotine are likely to be a reflection
      of a complex interplay between genetic factors that shape differences in
      expression and cellular architecture of this modulatory neurotransmitter system
      in the mammalian nervous system.

PMID- 14681930
TI  - Anatomical evidence for transsynaptic influences of estrogen on brain-derived
      neurotrophic factor expression.
AB  - Several studies have demonstrated that estrogen modulates brain-derived
      neurotrophic factor (BDNF) mRNA and protein within the adult hippocampus and
      cortex. However, mechanisms underlying this regulation are unknown. Although an
      estrogen response element (ERE)-like sequence has been identified within the BDNF
      gene, such a classical mechanism of estrogen-induced transcriptional activation
      requires the colocalized expression of estrogen receptors within cells that
      produce BDNF. Developmental studies have demonstrated such a relationship, but to
      date no studies have examined colocalization of estrogen receptors and BDNF
      within the adult brain. By utilizing double-label immunohistochemistry for BDNF,
      estrogen receptor-alpha (ER-alpha), and estrogen receptor-beta (ER-beta), we
      found only sparse colocalization between ER-alpha and BDNF in the hypothalamus,
      amygdala, prelimbic cortex, and ventral hippocampus. Furthermore, ER-beta and
      BDNF do not colocalize in any brain region. Given the recent finding that
      cortical ER-beta is almost exclusively localized to parvalbumin-immunoreactive
      GABAergic neurons, we performed BDNF/parvalbumin double labeling and discovered
      that axons from cortical ER-beta-expressing inhibitory neurons terminate on BDNF
      immunoreactive pyramidal cells. Collectively, these findings support a potential
      transsynaptic relationship between estrogen state and cortical BDNF: By directly
      modulating GABAergic interneurons, estrogen may indirectly influence the activity
      and expression of BDNF-producing cortical neurons.

PMID- 14681932
TI  - Expression of vesicular glutamate transporters in rat lumbar spinal cord, with a
      note on dorsal root ganglia.
AB  - Three vesicular glutamate transporters (VGLUTs) have been recently identified and
      their distribution has been mapped in various brain areas. In the present study,
      we used morphological approaches to investigate their expression in the rat
      lumbar spinal cord and dorsal root ganglia. Our results show a complementary
      distribution of VGLUT-expressing fibers in the spinal cord, with no overlapping
      in nerve endings. In the dorsal horn, VGLUT1 is most abundant in
      mechanosensory/proprioceptive deep afferent fibers. VGLUT2 and VGLUT3 are
      expressed only at moderate levels in primary sensory afferent fibers and are not
      used by central projections of nociceptive neurons. VGLUT1 and VGLUT2 mRNAs are
      mainly segregated in superficial laminae but colocalized in deeper laminae. Weak
      expression of VGLUT3 mRNA is only detected in deep laminae. The colocalization of
      VGLUT1 and VGLUT2 transcripts in most sensory neurons of the dorsal root ganglia
      is not in agreement with the clear segregation between the proteins in their
      spinal projections. Such a discrepancy suggests targeting mechanisms specific for
      each transporter and/or a distinct regulation of their translation. In the
      ventral horn, the expression of VGLUT1 and VGLUT2 mRNAs in motoneuron perikarya
      suggests the possible unexpected role of glutamate in the vertebrate
      neuromuscular junction. These results demonstrate the existence of different
      subpopulations of glutamate nerve terminals in the rat lumbar spinal cord and
      suggest that functionally distinct subsets of excitatory glutamatergic neuronal
      networks are involved in sensory processing and motor control.

PMID- 14681931
TI  - Organization of suprachiasmatic nucleus projections in Syrian hamsters
      (Mesocricetus auratus): an anterograde and retrograde analysis.
AB  - Circadian rhythms in physiology and behavior are controlled by pacemaker cells
      located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The mammalian
      SCN can be classified into two subdivisions (core and shell) based on the
      organization of neuroactive substances, inputs, and outputs. Recent studies in
      our laboratory indicate that these subdivisions are associated with functional
      specialization in Syrian hamsters. The core region, marked by calbindin-D(28K)
      (CalB)-containing cells, expresses light-induced, but not rhythmic, clock genes.
      In the shell compartment, marked by vasopressinergic cells and fibers, clock gene
      expression is rhythmic. Given these findings, an important question is how photic
      and rhythmic information are integrated and communicated from each of these
      regions to effector areas. The present study used localized, intra-SCN
      iontophoretic injections of the anterograde tracer biotinylated dextran amine
      (BDA) to investigate intra-SCN connectivity and the neural pathways by which
      information is communicated from SCN subregions to targets. Intra-SCN connections
      project from the core to the shell compartment of the SCN, but not from the shell
      to the CalB region of the SCN. Retrograde tracing experiments were performed
      using cholera toxin-beta (CTB) to determine more specifically whether SCN
      efferents originated in the core or shell using neurochemical markers for the
      rhythmic (vasopressin) and light-induced (CalB) SCN subregions. The combined
      results from anterograde and retrograde experiments suggest that all SCN targets
      receive information from both the light-induced and rhythmic regions of the SCN
      (albeit to varying degrees) and indicate that light and rhythmic information may
      be integrated both within the SCN and at target effector areas.

PMID- 14681933
TI  - Regional and subcellular compartmentation of the dopamine transporter and
      tyrosine hydroxylase in the rat ventral pallidum.
AB  - The ventral pallidum (VP) is a major intermediary in the prefrontal cortical
      circuitry regulating sensorimotor gating and locomotor behavior, both of which
      are potently modulated by catecholamines. The VP catecholaminergic innervation is
      derived from midbrain dopaminergic neurons that differ in expression levels of
      the dopamine transporter (DAT) and from brainstem noradrenergic neurons without
      DAT. The preferentially low level of DAT in dopaminergic terminals in the
      prefrontal cortex and in striatal regions projecting more extensively to the VP
      medial (VPm) compared with VP lateral (VPl) compartment suggests possible region
      specific differences in VP axonal distribution of DAT. To test this hypothesis,
      we examined the electron microscopic localization of DAT and the catecholamine
      synthesizing enzyme, tyrosine hydroxylase (TH), in the VPm and VPl of rat brain.
      In both regions, DAT and TH were localized primarily in small unmyelinated axons
      and morphologically heterogeneous axon terminals. DAT-immunogold particles were
      few in number, but mostly located on the plasma membrane. In contrast, TH
      immunoreactivity was distributed in the cytoplasm of individual profiles, many of
      which were without detectable DAT. In comparison with TH, the mean area density
      of DAT-labeled axons was low throughout the VP. The mean area density of DAT
      immunogold axon terminals, however, was significantly higher in VPl than in VPm,
      whereas that of TH-labeled axons was higher in VPm than in VPl. This dissociation
      suggests that, compared to the VPl, the VPm receives the greatest input from
      catecholaminergic afferents that are either nondopaminergic or characterized by
      having low levels or less terminal distributions of DAT.

PMID- 14681934
TI  - Connection from the dorsal column nuclei to the superior colliculus in the rat:
      topographical organization and somatotopic specific plasticity in response to
      neonatal enucleation.
AB  - Somatosensory stimuli from the body to deep and intermediate strata of the
      superior colliculus (SC) are relayed from the dorsal column nuclei (DCN), gracile
      (GrN) and cuneate (CuN). Electrophysiological studies have shown that the
      somatosensory representation in SC is arranged into a map-like pattern. However,
      there is a lack of studies confirming a morphological correlate of such an
      organization. On the other hand, after neonatal enucleation in rodents,
      somatosensory inputs ascend from their normal termination territory in
      intermediate and deep collicular strata to invade the more dorsally located
      visual strata. However, the origin of these reactive afferents has not been
      specified. By using anterograde (biotinylated dextran amine 10,000; BDA) and
      retrograde (Fluoro-Gold; FG) tracers, we studied separately the connection from
      GrN and CuN to the intact and neonatally deafferented SC. GrN-collicular
      afferents were found to terminate mainly within the periphery of the caudomedial
      SC quadrant, whereas CuN-collicular fibers innervated primarily the lateral part
      of the rostrolateral and caudolateral collicular quadrants, in a way consistent
      with previously described functional data. Retrograde tracing experiments using
      FG injected in SC confirmed this topographical arrangement. Injections of BDA in
      GrN or CuN of neonatally enucleated rats showed that reactive fibers reaching
      superficial strata are only those CuN-collicular fibers innervating the
      caudolateral SC quadrant, where the forelimb is represented. The present results
      provide an anatomical substrate for the known somatotopic organization of tactile
      representation in SC and further reinforce the previous proposal that the plastic
      reorganization of DCN-collicular afferents following neonatal enucleation
      constitutes a functional compensatory response.

PMID- 14681935
TI  - Rostral agranular insular cortex and pain areas of the central nervous system: a
      tract-tracing study in the rat.
AB  - The rostral agranular insular cortex (RAIC) has recently been identified as a
      site where local changes in GABA and dopamine levels, or application of opioids,
      can alter nociceptive thresholds in awake animals. The connections of the cortex
      dorsal to the rhinal fissure that includes the RAIC have been examined
      previously, with emphasis on visceral and gustatory functions but not
      nociception. Here we examined the afferent and efferent connections of the RAIC
      with sites implicated in nociceptive processing. Sensory information from the
      thalamus reaches the RAIC via the submedius and central lateral nuclei and the
      parvicellular part of the ventral posterior nucleus. The RAIC has extensive
      reciprocal cortico-cortical connections with the orbital, infralimbic, and
      anterior cingulate cortices and with the contralateral RAIC. The amygdala,
      particularly the basal complex, and the nucleus accumbens are important targets
      of RAIC efferent fibers. Other connections include projections to lateral
      hypothalamus, dorsal raphe, periaqueductal gray matter, pericerulear region,
      rostroventral medulla, and parabrachial nuclei. The connectivity of the RAIC
      suggests it is involved in multiple aspects of pain behavior. Projections to the
      RAIC from medial thalamic nuclei are associated with motivational/affective
      components of pain. RAIC projections to mesolimbic/mesocortical ventral forebrain
      circuits are likely to participate in the sensorimotor integration of nociceptive
      processing, while its brainstem projections are most likely to contribute to
      descending pain inhibitory control.

PMID- 14681936
TI  - Radial glia produce and align the ligand fibronectin during neuronal migration in
      the developing chick brain.
AB  - We demonstrated previously that alpha8beta1 integrin regulates the migration and
      survival of immature neurons during development of the chicken optic tectum;
      however, the potential extracellular ligand was unknown. We used
      immunohistochemistry to determine if several potential ligands (fibronectin,
      tenascin, vitronectin, and osteopontin) were expressed during neuronal migration
      along radial glia (RG). Fibronectin was localized in a pattern relevant to radial
      migration and survival of neurons; it was present before and during neuronal
      migration and appeared oriented along RG fibers by conventional fluorescence
      microscopy. Confocal microscopy confirmed that fibronectin was localized along RG
      cells during radial migration. It was more concentrated in some superficial
      laminae, which might support directional movement. Fibronectin was present after
      formation of definitive tectal laminae, but was diffuse and not aligned along RG,
      which persist. Flow cytometry analysis of dissociated optic tectum cells revealed
      that almost all RG were positive for fibronectin. Short-term cell culture
      experiments using an exocytosis inhibitor revealed that fibronectin accumulated
      in most RG cells. Thus, fibronectin is produced by RG and is aligned along their
      surfaces before and during migration. Fibronectin, therefore, is a potential
      ligand for general radial neuronal migration in the chick optic tectum. Its
      predominant source appears to be RG, in contrast with developing mammalian
      cortex, where fibronectin was not found in a pattern that could guide widespread
      radial migration and where neurons are the predominant producers of fibronectin
      during migration.

PMID- 14681937
TI  - Definition and connections of the entopallium in the zebra finch (Taeniopygia
      guttata).
AB  - In birds the entopallium (formerly known as the core region of ectostriatum) is
      the major thalamorecipient zone, within the telencephalon, of the tectofugal
      visual system. Here we sought to redefine the entopallium in the zebra finch,
      particularly with respect to a laterally adjacent zone, known as the
      perientopallium (formerly known as the periectostriatal belt), and to determine
      its projections. We show that the entopallium can be defined by the almost
      complete overlap of dense terminations of thalamic rotundal afferents and intense
      cytochrome oxidase activity and parvalbumin immunoreactivity. The
      perientopallium, on the other hand, can be defined by relatively sparse
      projections from nucleus rotundus, a calretinin-positive plexus of nerve fibers,
      and weak cytochrome oxidase activity and parvalbumin immunoreactivity. Within the
      entopallium, medial and lateral parts can be distinguished on the basis of cell
      packing density, differential patterns of parvalbumin immunoreactivity and
      cytochrome oxidase activity, and different projections. We show that the
      entopallium projects laterally and diffusely to the perientopallium and
      nidopallium (formerly the neostriatum) and specifically and densely to a teardrop
      shaped nucleus in the ventrolateral mesopallium (formerly known as the
      hyperstriatum ventrale), here called MVL (abbreviation used as a proper name).
      This latter projection arises predominantly from medial parts of the entopallium,
      which also receives a reciprocal projection from MVL, and projects to the lateral
      striatum. These findings suggest that the entopallium can be divided into medial
      and lateral parts having different functions, one of which is to provide for an
      extratelencephalic outflow from the medial part, via the lateral striatum. The
      findings also challenge the idea that informational flow through the various
      stations of the telencephalic tectofugal visual system is largely sequential and,
      together with findings in the chicken (Alpar and Tombol), suggest instead that
      further substantial projections to telencephalic visual areas in birds can arise
      independently from both E (entopallium) and Ep (perientopallial belt).

PMID- 14681938
TI  - Glandular cell atypia on Papanicolaou smears: interobserver variability in the
      diagnosis and prediction of cell of origin.
AB  - BACKGROUND: The 2001 Bethesda System recommended qualification of atypical
      glandular cells (AGC) to indicate the site of origin and separated endocervical
      adenocarcinoma in situ (AIS) from "AGC favor neoplastic" as a specific diagnostic
      category. To the authors' knowledge, the literature evaluating the
      reproducibility of Papanicolaou (Pap) smear diagnosis of glandular cell
      abnormalities with emphasis on the cell of origin is limited. The aim of the
      current study was to investigate whether a variety of benign to neoplastic
      glandular lesions can be reliably classified on Pap smear with regard to
      diagnosis and cell of origin. METHODS: Twenty-three conventional Pap smears (CPS)
      with glandular cellular changes varying from benign to adenocarcinoma (ACA) were
      reviewed by six observers. They were asked to categorize each smear according to
      cell of origin (endocervical vs. endometrial) and diagnosis (benign, AGC, or
      ACA). Kappa statistics were used to evaluate interobserver agreement and
      correlation of interobserver agreement with experience. RESULTS: There was no
      consensus among observers for both the origin of the cells and the diagnosis.
      Interobserver agreement for site was poor (kappa < 0.4) especially in the AGC
      category. Unanimous agreement for site was reached for 7 of 23 smears (30%). Two
      of five endocervical AIS were classified as endometrial and another two were
      classified as benign by four observers. Interobserver agreement was poor in all
      diagnostic categories (kappa < 0.4) and showed slight correlation with level of
      experience. Unanimous agreement for diagnosis was reached for only 2 smears (9%).
      Three of 11 (27%) smears demonstrating preneoplastic/neoplastic processes were
      diagnosed as benign by 3 observers. Three (25%) benign CPS were diagnosed as ACA
      by 2 observers. Accurate prediction of the final histologic diagnosis by
      observers varied from 30% to 87% and did not correlate closely with experience.
      CONCLUSIONS: Cytologic diagnosis of glandular lesions by CPS was problematic and
      suffered from significant interobserver subjectivity.

PMID- 14681939
TI  - Liquid-based cytology and conventional cervical smears: a comparison study in an
      Asian screening population.
AB  - BACKGROUND: This study compared the findings of cervical cytology screening by
      ThinPrep Papanicolaou (Pap) tests (TP) with the findings of screening by
      conventional cervical smears (CS) in a screening population involving what to the
      authors' knowledge is the largest sample of ThinPrep Pap tests published to date.
      METHOD: Data from 191,581 CS that were screened in the period from March 1, 1998
      to February 28, 2000 were compared with data from 190,667 TP performed from March
      1, 2000 to February 28, 2002 and that were obtained from the same sources.
      RESULTS: With TP, the unsatisfactory rate was reduced from 0.48% to 0.32%. Fewer
      cases were considered to be suboptimal (19.12% vs. 12.97%). The detection rates
      of squamous cell carcinomas, adenocarcinomas, and high-grade squamous
      intraepithelial lesions (HSIL) were essentially unchanged in the TP group
      (0.005%, 0.003%, and 0.25%, respectively) compared with the rates for the CS
      group (0.01%, 0.006%, and 0.25%, respectively). There was an increase in the
      detection of atypical squamous cells of undetermined significance (ASCUS; 3.74%
      vs. 3.19%) and low-grade SIL (LSIL; 1.67% vs. 1.01%) with a decrease in the ASCUS
      to-LSIL ratio from 3.15 for CS to 2.33 for TP. The detection of atypical
      glandular cells of undetermined significance (AGUS) increased slightly from 0.07%
      to 0.09%. The proportion of cells reported to have reactive atypia dropped from
      2.71% to 1.48%. Limited biopsy correlation (range, 73.2-76.2%) confirmed the
      increased sensitivity of TP. More actinomyces (1.07% vs. 0.52%) were detected in
      TP samples despite of a similar portion of intrauterine-device users. The average
      primary screening and rapid rescreening time of each slide were reduced from 8
      minutes to 4 minutes and from 2 minutes to less than 1 minute, respectively.
      CONCLUSIONS: The preliminary experience of the authors of the current study
      appears to support the use of the ThinPrep Pap test to enhance the efficiency of
      cervical cytology screening.

PMID- 14681940
TI  - Improvement in protection against adenocarcinoma of the cervix resulting from
      participation in cervical screening.
AB  - BACKGROUND: The incidence of adenocarcinoma of the cervix did not decline in
      Western countries in the 1970s and 1980s despite the availability and use of
      cervical cytologic screening. The impact of improved endocervical sampling and
      better recognition of the cytologic precursors to adenocarcinoma during the 1990s
      in reducing the risk of adenocarcinoma is currently unknown. METHODS: Using
      records from a statewide registry, the authors compared the screening histories
      of 160 women with adenocarcinoma (33 microinvasive cases and 127 invasive cases)
      who were diagnosed between 1995 and 2001 with the screening histories of 640
      control women in a matched case-control study. RESULTS: A decreased risk of
      invasive adenocarcinoma was associated with a recent negative Papanicolaou (Pap)
      smear and at least one smear with an endocervical component since 1994. An
      increased risk of invasive adenocarcinoma was associated with a history of
      previous cervical abnormalities and greater than 5 years between Pap smears.
      There was no significant difference between cases and controls with regard to the
      number of negative Pap smears. There was little apparent difference in the
      screening histories of patients with microinvasive tumors and the controls, with
      the control women appearing to have no greater relative protection than the
      cases. With biennial screenings, the authors estimate that a 46% reduction in the
      cumulative incidence of invasive adenocarcinoma could be achieved, and with
      annual screening, a 65% reduction could be achieved. CONCLUSIONS: The incidence
      of cervical adenocarcinoma should begin to decline in the current decade among
      screened women.

PMID- 14681941
TI  - ThinPrep versus conventional Papanicolaou smear in the cytologic follow-up of
      women with equivocal cervical smears.
AB  - BACKGROUND: The purpose of the current study was to compare the efficacy of
      liquid-based cytology and conventional smears in the cytologic follow-up of cases
      with "atypical squamous cells, cannot exclude a high-grade lesion" (ASC-H) or
      "atypical glandular cells" (AGC). METHODS: Cytologic follow-up was performed on
      214 cases with ASC-H/AGC diagnosis an conventional smears using either ThinPrep
      (n = 100) or conventional Papanicoloau (Pap) tests (n = 114). Results were then
      compared with further histologic and/or cytologic follow-up. RESULTS: Repetition
      on conventional smears enabled a definite diagnosis (within normal limits [WNL],
      squamous intraepithelial lesion [SIL] or carcinoma) in 58 cases (50.9%). ASC/AGC
      was confirmed in 50 cases (43.9%), and 6 of the smears (5.3%) were inadequate.
      WNL, SIL, or carcinoma was diagnosed in 82 (82.0%) cases by following the
      patients with ThinPrep cytology, whereas ASC or AGC was confirmed in 18 cases
      (18.0%). No inadequate specimens were found. A diagnosis of SIL or greater (SIL
      +) was confirmed histologically in 11 of 11 (100.0%) conventional smears and in
      31 of 34 (91.2%) ThinPrep specimens. Of the 87 WNL specimens, 9 (8 conventional
      smears and 1 ThinPrep specimen) developed a histologically confirmed SIL during
      further follow-up. Specimen adequacy was significantly better in the ThinPrep
      specimens compared with conventional smears. CONCLUSIONS: Because of better
      specimen adequacy, ThinPrep cervical cytology appears to significantly reduce the
      occurrence of ASC/AGC compared with conventional Pap smears.

PMID- 14681942
TI  - Touch imprint cytology of axillary lymph nodes after neoadjuvant chemotherapy in
      patients with breast carcinoma.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NC) reportedly downstages axilla in
      approximately one-third of patients with locally advanced breast carcinoma
      (LABC). Postchemotherapy axillary lymph node status is an important prognostic
      factor. In the current study, the authors evaluated the reliability of touch
      imprint cytology (TIC) in detecting axillary lymph node metastasis after NC and
      identified chemotherapy-induced changes that may influence this assessment.
      METHODS: Thirty-three patients with LABC were studied. Seventeen patients had
      received chemotherapy before surgery (NC group) and 16 patients had not (non-NC
      group). Touch imprints were made from either the largest axillary lymph node (in
      13 patients from the NC group and 16 patients from the non-NC) or the sentinel
      lymph node (in 4 patients from the NC group). Imprints from the NC group were
      evaluated for metastasis and were correlated with histopathology. Touch imprints
      from both groups were compared for cellularity, tumor load,
      necrosis/degeneration, and histiocytes. RESULTS: Cytologic evaluation for
      metastasis was 100% concordant with histopathology in all 17 patients from the NC
      group (9 positive results [53%] and 8 negative results [47%]). The presence of
      few tumor cells in sparsely cellular imprints that exhibited necrosis (two
      patients) and the presence of only degenerating/necrotic tumor cells (two
      patients) were two cytologic patterns unique to post-NC imprints that may have
      influenced their accurate assessment. CONCLUSIONS: TIC was found to be reliable
      for the intraoperative evaluation of axillary lymph node metastasis after NC.
      However, a careful examination is warranted in sparsely cellular imprints,
      because there is the possibility of overlooking a small group of tumor cells. To
      the authors' knowledge, the significance of finding extensive necrosis in
      axillary lymph nodes after NC is not known and may be investigated.

PMID- 14681943
TI  - Urethral wash cytopathology for monitoring patients after cystoprostatectomy with
      urinary diversion.
AB  - BACKGROUND: Urethral wash cytopathology (UWC) has been recommended for monitoring
      patients after cystoprostatectomy with preservation of the penile urethra and
      urinary diversion. The rationale has been that early detection of urethral
      neoplasms (recurrences) would allow for urethrectomy to be performed before an
      invasive tumor developed and thus prevent or delay disease progression. Negative
      results of UWC would spare the patient a major surgical procedure. The authors
      analyzed the clinical and pathologic records of patients undergoing
      cystoprostatectomy with urinary diversion and preservation of the penile urethra
      to determine the cytohistologic correlations and to document the effect of UWC
      monitoring on the rate of disease progression. METHODS: All cases of men
      undergoing a cystoprostatectomy with urinary diversion and preservation of the
      penile urethra over a 12-year period at the study institution were included.
      Records were reviewed to determine the degree of risk associated with the
      pathologic findings at surgery and to document the presence or absence of disease
      progression for each individual. The pathologic specimens of all cases monitored
      with UWC were reviewed separately by both authors to establish cytohistologic
      correlations. Standard statistical methods were applied. RESULTS: Of 176
      patients, urethral recurrence and disease progression occurred in both high-risk
      and low-risk groups. Among the 48 individuals monitored with UWC, 13 had a
      positive diagnosis, and 10 of these 13 had been subsequently treated with
      urethrectomy. Among 128 patients not monitored with UWC, 16 underwent
      urethrectomy. Patients in both groups had recurrent urethral neoplasms. Most
      lesions were focal carcinomas in situ occupying the paraurethral glands. One
      individual in each group had no further disease progression, even though the
      urethral tumor was invasive. Urethrectomy was found to have no statistically
      significant association with the rate of disease progression, regardless of
      whether the procedure resulted from a positive UWC or was provoked by
      patient/clinician concern. When groups were compared on the basis of monitoring
      with UWC, there was no statistical difference in the rate of disease progression
      between those monitored with UWC and those who were not. Within the monitored
      group, however, the cytopathologic interpretations of UWC were statistically
      significant; patients with positive findings were found to have the highest rate
      of disease progression, and those with negative findings experienced the lowest
      (P < 0.04). CONCLUSIONS: Both monitoring with UWC and urethrectomy might benefit
      selected individuals, but neither method appeared to have a statistically
      significant effect on disease progression in a nonrandomized group of patients. A
      positive UWC was associated with a high likelihood of disease progression and
      could justify more intensive follow-up for progressive disease at other sites.

PMID- 14681944
TI  - The use of fine-needle aspiration cytology and core biopsy in the assessment of
      highly suspicious mammographic microcalcifications: analysis of outcome for 182
      lesions detected in the setting of a population-based breast cancer screening
      program.
AB  - BACKGROUND: Fine-needle aspiration biopsy (FNAB) is used as the first-line
      diagnostic test for lesions that require morphologic assessment in the authors'
      breast cancer screening program. A positive cytologic diagnosis is an indication
      to proceed to definitive surgery. Core biopsy is used if FNAB is not diagnostic.
      In the context of increased use of core biopsy at other centers, the authors
      reviewed their experience with the cytologic assessment of highly suspicious
      microcalcifications. METHODS: Between January 1996 and June 2000, the dominant
      radiologic abnormality was classified prospectively as high-grade
      microcalcifications in 182 lesions. Data were recorded on patient demographics,
      radiologic features, and the findings of FNAB and core biopsy, if performed. The
      results of the screening assessment were then compared with the final histologic
      findings. RESULTS: Overall, 15.6% of all radiologically high-grade lesions were
      microcalcifications. The mean patient age was 58.76 years. The lesions had a mean
      size of 38.49 mm (range, 5-200 mm), and 92.31% of high-grade microcalcifications
      proved to be malignant. Among the cases evaluated by FNAB, a positive cytologic
      diagnosis of malignancy was made in 70.93% of lesions, without any false-positive
      diagnoses and obviating the need for diagnostic core biopsy. FNAB had a
      sensitivity of 77.22% and a positive predictive value (PPV) of 100%. When core
      biopsy was performed due to the absence of a positive cytologic diagnosis, it
      averted the need for open biopsy in 76% of lesions. CONCLUSIONS: Where there is
      access to skilled cytopathologists, FNAB can provide a highly accurate, rapid,
      and cost-effective means of triage of patients who would benefit most from the
      more expensive core biopsy.

PMID- 14681945
TI  - MUC1 and MUC2 expression in pancreatic ductal carcinoma obtained by fine-needle
      aspiration.
AB  - BACKGROUND: Mucins are high molecular weight glycoproteins that are produced by
      various epithelial cells including those found in the pancreas. MUC1 and MUC2 are
      two well characterized mucin antigens. The objective of the current study was to
      examine the pattern of phenotypic expression of MUC1 and MUC2 in pancreatic
      lesions obtained by fine-needle aspiration biopsy (FNA) and to determine the
      utility of MUC1 and MUC2 as markers for pancreatic ductal carcinoma. METHODS:
      Thirty-nine cell blocks of pancreatic FNA obtained under endoscopic ultrasound
      guidance were retrieved from the archives and immunostained with a monoclonal
      antibody directed against MUC1 and MUC2. These cell blocks were taken from 39
      patients (16 females and 23 males) who had a median age of 64 years. Eleven FNAs
      were taken from patients with reactive/inflammatory conditions. The remaining 28
      FNAs included 24 ductal carcinomas, 2 neuroendocrine tumors, 1 lymphoma sample,
      and 1 sarcoma sample. The presence of immunoreactivity, irrespective of the level
      of intensity or the percentage of cells, was considered as positive for MUC1 and
      MUC2 expression. Follow-up included correlation with pathology materials obtained
      at surgery and review of medical records. RESULTS: Twenty-three of 24 pancreatic
      ductal carcinomas (96%) demonstrated positive staining with MUC1. Twenty-one
      positive cases demonstrated either apical or diffuse membranous staining with
      variable cytoplasmic staining. The remaining two positive cases showed only
      cytoplasmic staining. One of the 11 cases of chronic pancreatitis and benign
      conditions demonstrated weak apical membranous MUC1 staining in the acinic cells.
      The difference between the two groups was statistically significant (P < 0.001,
      using the Fisher exact test). Three pancreatic ductal carcinomas and one chronic
      pancreatitis specimen demonstrated cytoplasmic staining with MUC2; the difference
      between the two groups was not found to be statistically significant. None of the
      nonductal neoplasms demonstrated expression of either MUC1 or MUC2. The
      sensitivity and specificity of MUC1 as a marker for pancreatic ductal carcinomas
      were 96% and 94%, respectively. CONCLUSIONS: MUC1 is overexpressed in pancreatic
      ductal carcinoma with a predominantly membranous and variable cytoplasmic
      staining pattern. The results of the current study suggest that the phenotypic
      expression of MUC1 can be used as an ancillary marker for diagnosing pancreatic
      ductal carcinoma in cytologic preparations. Conversely, MUC2 does not appear to
      be a useful marker for recognizing pancreatic ductal carcinoma in FNA specimens.

PMID- 14681946
TI  - Adenosquamous carcinoma of the pancreas: cytologic features in 14 cases.
AB  - BACKGROUND: Adenosquamous carcinoma (ASCa) is a rare subtype of ductal
      adenocarcinoma of the pancreas with what to the authors' knowledge are limited
      cytologic descriptions. In the current study, the authors describe their
      experience with the fine-aspiration biopsy (FNAB) diagnosis of ASCa and
      characterize cytologic features in 14 cases. METHODS: Fourteen cases of ASCa were
      identified from pathology case files. Cytologic material was examined for
      cellularity, grade, tumor cell necrosis, and specific features of glandular and
      squamous differentiation. RESULTS: The 10 females and 4 males had an average age
      of 70 years. Nine patients (64%) were reported to have Stage IV disease at the
      time of presentation. All tumors were high grade, with moderate to high
      cellularity. Tumor cell necrosis was noted in 12. Nine of the 14 cases (64%)
      demonstrated predominantly squamous differentiation with keratinization. Seven of
      these nine contained at least focal intracellular mucin or honeycombed glandular
      sheets. Two of the nine had rare cytoplasmic vacuoles as the only evidence of
      glandular differentiation. Five cases (36%) were predominantly glandular. All but
      one of these five cases contained atypical to malignant keratinized cells. One of
      the five cases lacked keratinization but had tumor cells with dense cytoplasm;
      the diagnosis of ASCa was confirmed on histology. In 13 patients for whom
      followup was known, 12 had died of disease (mean, 5.6 months) and 1 was alive at
      13 months of follow-up. CONCLUSIONS: A specific diagnosis of ASCa is possible
      when aspirates show evidence of both squamous and glandular differentiation,
      although one component often predominates and features of dual differentiation
      may be focal. A purely squamous tumor should raise the suspicion of a metastasis,
      but also may represent undersampling of an ASCa.

PMID- 14681947
TI  - Comparative molecular analysis of loss of heterozygosity in adenocarcinoma in
      bile duct brushings and corresponding surgical pathology specimens.
AB  - BACKGROUND: Bile duct brushing is the procedure of choice for the assessment of
      neoplasia of the biliary and pancreatic ducts. Conventional cytopathologic
      evaluation has been reported to have high specificity but relatively low
      sensitivity. Although a number of molecular studies regarding biliary tract
      tissue specimens have been performed, to the authors' knowledge their precise
      applicability to cytopathology specimens has not been critically analyzed.
      METHODS: Bile duct brushing specimens with the cytopathologic diagnosis of
      "suspicious" or "positive for malignant cells" along with corresponding surgical
      pathology specimens demonstrating adenocarcinoma were searched for in the files
      of UPMC-Presbyterian Hospital for the years 1990-1996. Tumor cells from
      representative cytopathology and histology slides were microdissected and
      analyzed for loss of heterozygosity (LOH) in a panel of microsatellite markers.
      The results obtained from cytopathologic and surgical pathology specimens were
      compared. RESULTS: Eight paired surgical and cytopathology cases of
      adenocarcinoma involving the biliary tract were identified. The fractional
      allelic loss (FAL) for the surgical specimens (FAL-S) ranged from 12.5-71.4% and
      the FAL for the cytopathology specimens (FAL-C) ranged from 25-71.4%. However,
      when evaluating the actual loci of LOH, the concordance rate of the surgical and
      cytopathology specimens ranged from 71.4-100% (mean, 88.6%). Only 3 of the 8
      cases (37.5%) were found to have identical matching of the LOH loci. CONCLUSIONS:
      Although the overall concordance rate of LOH in biliary cytology and surgical
      specimens by molecular analysis is relatively high, the issue of molecular
      tumoral heterogeneity must be considered if clinical decisions are to be based
      exclusively on cytopathologic analysis.

PMID- 14681948
TI  - Evaluation of interphase fluorescence in situ hybridization for the
      t(14;18)(q32;q21) translocation in the diagnosis of follicular lymphoma on fine
      needle aspirates: a comparison with flow cytometry immunophenotyping.
AB  - BACKGROUND: Diagnosing lymphoproliferative disorders on fine-needle aspiration
      (FNA) can be challenging due to variable cellularity and lack of architecture.
      Ancillary studies often are required for diagnosis. Follicular lymphoma (FL) is
      characterized by a monoclonal B-cell proliferation with coexpression of CD19/CD10
      and a t(14;18)(q32;q21) reciprocal translocation, resulting in the immunoglobulin
      heavy chain/BCL-2 fusion gene. These features also can be found, with much lower
      frequency, in diffuse large B-cell lymphoma (DLBCL) of follicle center cell
      origin. The objective of the current study was to compare the accuracy in
      detecting FL and DLBCL of follicle center cell origin by interphase fluorescence
      in situ hybridization (I-FISH) versus flow cytometry immunophenotyping (FCM) on
      FNAs. METHODS: Concurrent testing by FISH for t(14;18)(q32;q21) and FCM was
      performed on 84 FNAs, including 40 FLs and 44 non-FLs (de novo DLBCLs, mantle
      cell lymphomas, small lymphocytic lymphomas/chronic lymphocytic leukemias
      [SLLs/CLLs], small B-cell lymphomas, and reactive lymphoid hyperplasias). The
      final diagnosis was rendered based on the combined information from
      cytomorphology, FCM, FISH, immunocytochemical staining for Ki-67, monoclonality
      for kappa and lambda light chains, and, if available, corresponding tissue
      biopsy, cytogenetic analysis, and polymerase chain reaction analysis. RESULTS:
      Among 40 FLs, FISH produced positive results for the t(14;18) translocation in
      85.0%, negative results in 7.5%, and insufficient results in 7.5%; whereas, with
      FCM, 75% of cases exhibited a CD19-positive (CD19+)/CD10+ population (28
      monoclonal, 2 nonclonal), 12.5% of cases exhibited a CD19+/CD10-negative
      population (3 monoclonal, 2 nonclonal), and 12.5% of cases were insufficient. All
      of nonclonal results from FCM and all of the insufficient results from FCM
      analysis exhibited unequivocal t(14;18) translocation by FISH. In contrast, the
      three negative results and the three insufficient results from FISH were
      monoclonal and CD19+/CD10+ on FCM. The results from FISH and FCM were concordant
      in 75% cases. Of 44 non-FLs, FISH produced positive results for the t(14;18)
      translocation in 5 DLBCLs and 2 SLLs/CLLs. The latter showed single fusion
      signals just above the cutoff level. All cases in the non-FL group that failed to
      show clonality or had insufficient results from FCM were DLBCLs. Among 17 DLBCLs,
      FISH detected a t(14;18) translocation in 29.4%, whereas FCM demonstrated a
      CD19+/CD10+ population in 23.5%. CONCLUSIONS: I-FISH for the t(14;18)(q32;q21)
      translocation provided high overall accuracy in detecting FLs on FNAs. This test
      can be used for diagnosing or monitoring FL on FNAs when cellularity is limited
      or when FCM results are noncontributory. For detecting a follicle center cell
      origin in DLBCLs, I-FISH for the t(14;18) translocation appeared to be slightly
      more sensitive than FCM for the CD19+/CD10+ immunophenotype.

PMID- 14681949
TI  - Can intensive three-day programmes improve nurses' communication skills in cancer
      care?
AB  - Effective communication is widely regarded as a crucial component of patient care
      that can determine patient satisfaction, compliance and recovery. The plethora of
      communication skills training programmes available to health professionals is
      also a testament to the importance of this element of care. However a review of
      studies evaluating the effectiveness of such training programmes concluded that
      little behavioural change in health professionals' communication skills was
      evident. This paper reports the findings of a programme offered to
      cancer/palliative care nurses (n=108) via eight condensed three-day workshops at
      various UK venues. Behavioural change was assessed through evaluation of
      audiotaped nursing assessments made pre- and six weeks post-course, scored along
      nine previously identified key communication areas. Mean overall scores rose by 6
      points ( p<0.001) to 20 (out of 27) with statistically significant improvements
      on eight of the nine individual areas. Improvements in subjective levels of
      confidence in the areas of communication found difficult pre-course were observed
      immediately post-course ( p<0.001) and were still evident six weeks later.
      Similar improvements immediately post-course for teaching communication skills to
      colleagues ( p<0.001) were further improved six weeks post-course for seven of
      the eight areas assessed. These results suggest that three-day training courses
      can lead to clinically relevant behavioural change and improvements in perceived
      confidence in communication and dissemination of skills.

PMID- 14681950
TI  - A three-year study of chaplains' professional activities at Memorial Sloan
      Kettering Cancer Center in New York city.
AB  - The pastoral-care interventions of chaplains at Memorial Sloan-Kettering Cancer
      Center were documented during two-week periods in each of three years. The study
      describes the pattern of referrals to and from chaplains and the kinds of
      interventions performed during the chaplains' contacts with patients and their
      families and friends. Nearly a fifth of all chaplain interventions were the
      result of referrals. The vast majority of staff referrals to chaplains came from
      nurses, with the frequency and proportion of referrals from nurses significantly
      increasing over time. More than a third of all chaplain contacts were with
      friends and family without the patient present, and over 40% of referrals to
      chaplains were for the friends and family of patients. Pastoral visits were
      significantly shorter when patients were not present. In particular, pastoral
      care interventions were found to differ according to the patient's religion and
      the circumstances of the chaplain's visit to the patient (i.e. patient status).
      Visit duration also varied by patient status, with pre-operative visits being
      significantly shorter than post-operative or treatment visits.

PMID- 14681951
TI  - Prostate cancer patients' support and psychological care needs: Survey from a non
      surgical oncology clinic.
AB  - While there are numerous uncertainties surrounding prostate cancer's detection
      and treatment, more research focusing on the psychological needs of prostate
      patients is required. This study investigated the support and psychological care
      needs of men with prostate cancer. Patients were approached during urological
      oncology clinics and asked to complete the: Support Care Needs Survey (SCNS),
      Support Care Preferences Questionnaire, EORTC QLQ-C30 (Version 3) Measure plus
      Prostate Module, and the Hospital Anxiety and Depression Scale (HADS). Of the 249
      patients meeting study entry criteria, there was an 89% response rate resulting
      in a cohort of 210 patients. The data showed that significant unmet need exists
      across a number of domains in the areas of psychological and health
      system/information. The more commonly reported needs were 'fears about cancer
      spreading (44%),' 'concerns about the worries of those close to you (43%),' and
      'changes in sexual feelings (41%).' Half of all patients reported some need in
      the domain of sexuality, especially men younger than 65 years. Needs were being
      well met in the domain of patient care and support. A significant number of
      patients reported having used or desiring support services, such as information
      about their illness, brochures about services and benefits for patients with
      cancer (55%), a series of talks by staff members about aspects of prostate cancer
      (44%), and one-on-one counselling (48%). Quality of life (QoL) was most
      negatively impacted in those who: were < or =65 years old, had been diagnosed
      within one year, or had metastatic disease. Men < or =65 had decreased social
      functioning, greater pain, increased sleep disturbance, and were more likely to
      be uncomfortable about being sexually intimate. Patients recently diagnosed had
      increased fatigue, more frequent urination, greater disturbance of sleep, and
      were more likely to have hot flushes. Those with advanced disease scored lower on
      12 out of 15 QoL categories. PSA level had no effect on QoL or anxiety/depression
      scores. Men with advanced disease had greater levels of depression and those < or
      =65 years old were more likely to be anxious. Although most men with prostate
      cancer seem to function quite well, a substantial minority report areas of unmet
      need that may be targets for improving care.

PMID- 14681952
TI  - Receiving a screen-detected diagnosis of cancer: the experience of participants
      in the UK flexible sigmoidoscopy trial.
AB  - The experience of receiving a screen-detected diagnosis of colorectal cancer was
      explored using open-ended interviews. Twenty four people who had been diagnosed
      with cancer at flexible sigmoidoscopy screening were interviewed at their homes
      over the telephone. Thematic analysis of the transcripts showed that the
      experience of gaining a diagnosis of cancer through screening was characterised
      by a lack of prior expectation that cancer would be detected and feelings of
      shock. This was largely because of the absence of symptoms and current feelings
      of well-being. Some interviewees expressed feelings of relief and gratitude at
      having cancer diagnosed at an early enough stage that 'something could be done
      about it'. The experience of receiving a screen-detected diagnosis could be
      summarised as one of 'moderated shock' whereby the shock of the unexpected
      diagnosis was often moderated by the news that the cancer had been caught early.
      Whilst these screen-detected cancers were diagnosed relatively rapidly, a
      significant number of interviewees had a period in which they were effectively
      'symptomatic' (e.g. knew they had an adenoma but did not know whether it was
      malignant or benign). However, they did not use this period to prepare themselves
      for a possible cancer diagnosis. Raising awareness of the adenoma-carcinoma
      sequence may help reduce the shock of a screen-detected diagnosis. However, any
      interventions aimed at reducing the distress of a screen-detected cancer would
      need to consider the overall benefit to screening attenders, most of whom will
      have benign polyps detected.

PMID- 14681953
TI  - The CARES-SF used for prospective assessment of health-related quality of life
      after stem cell transplantation.
AB  - OBJECTIVE: By employing the Cancer Rehabilitation and Evaluation System short
      form (CARES-SF) prospectively we wanted to focus on the rehabilitation needs
      after high-dose chemotherapy (HDC) and stem cell transplantation, in order to
      identify problems that should be addressed by health-care professionals during
      the course of disease and treatment. METHODS: The CARES-SF was administered
      before and at 2, 6 and 12 months post-transplant to 130 cancer patients treated
      with HDC and allogeneic (SCT) or autologous stem cell transplantation (ASCT).
      Physical function scale scores were compared with the corresponding scale of the
      EORTC QLQ-C30. RESULTS: The SCT group reported significantly better physical
      function than the ASCT group before transplant on both the CARES-SF (p<0.0001)
      and the EORTC QLQ-C30 (p<0.01). Almost identical mean CARES-SF scores across
      groups (SCT: 0.7-1.4, ASCT: 0.8-1.3) were found at the subsequent assessments,
      consistent with the QLQ-C30 data. Correlations between CARES-SF and QLQ-C30
      Physical Function Scales ranged from 0.45 to 0.65. The SCT group had better
      psychosocial subscale scores (mean 0.4 and 0.5 versus ASCT: 0.7 and 0.8, p <
      0.01) at the 6 and 12-month assessments, as well as better satisfaction on the
      marital subscale ( p=0.01) 6 months post-transplant. Few patients requested
      specific help: 19% at baseline with 'fear of the cancer progressing' and 9% with
      'reduction in physical energy' after 6 and 12 months. CONCLUSION: The CARES-SF
      detected differences across groups of patients as well as within-patient changes
      over time. The possibility for patients to express their need for professional
      assistance renders the CARES-SF appropriate after SCT/ASCT. The sexual, marital
      and medical interaction subscales in particular address specific issues of
      relevance for follow-up care, compared with more traditional questionnaires
      assessing health related quality of life (HRQOL).

PMID- 14681954
TI  - Course of distress and quality of life in testicular cancer patients before,
      during, and after chemotherapy: results of a pilot study.
AB  - Testicular cancer is the most common cancer in white males between the ages of 15
      and 45 years. Treatment may include the administration of chemotherapy which has
      been associated with changes in emotional distress, quality of life, and symptom
      distress in other cancers. The current study was designed to evaluate the course
      of these constructs in a sample of testicular cancer patients undergoing
      chemotherapy. Patients completed measures of emotional distress and quality of
      life prior to, during, and after chemotherapy, with symptom distress measured
      during chemotherapy. Thirty percent of patients reported moderate to high levels
      of distress at pre-treatment baseline that was associated with worse quality of
      life. Initial anxiety and distress decreased and stayed low through chemotherapy
      and post-treatment follow-up. There were no significant changes in fatigue,
      nausea or change in appearance during chemotherapy. The results suggest that some
      patients evidence pre-treatment anxiety and distress that appears to be primarily
      anticipatory, decreases over the course of chemotherapy, and occurs in the
      context of improved quality of life and reduced symptom severity. Deleterious
      changes in emotional distress, quality of life, and symptom distress seen in
      other cancer populations were not apparent in our sample of testicular cancer
      patients.

PMID- 14681955
TI  - Perception of breast cancer risk and surveillance behaviours of women with family
      history of breast cancer: a brief report on a Spanish cohort.
AB  - Women with a family history of breast cancer (FHBC) are at increased risk for
      developing this disease. In this study, we have investigated the differences
      between two groups of women; those with family history of breast cancer (N=42)
      and women at population risk (N=42) in a Spanish cohort. Questionnaires assessed
      distress, perception of breast cancer risk, screening behaviours, coping skills,
      personality and quality of life. Neither group received genetic counselling
      before or after this study. Women with FHBC overestimated their risk of
      developing breast cancer. They report a subjective risk of developing breast
      cancer of 50%, with their actual risk, using the risk tables elaborated by Claus
      et al., being only 15% (p<0.05). Discriminant function analysis revealed the
      patients' information about breast cancer, worries about breast cancer,
      perception of risk based on family history, perception of lifetime risk of breast
      cancer and quality of life were the five variables that distinguished between
      both groups. Only 34% of women in the FHBC group performed monthly breast self
      examination, 24% (10 subjects) had never attended previously for clinical breast
      examination and 45% (19 subjects) had never undergone a mammogram. This group of
      women had a significantly lower level of general satisfaction (p<0.05), an
      indicator of Quality of Life. The results support the need for developing
      psychological intervention for women with family history of breast cancer in
      order to increase adherence to surveillance behaviours, reduce distress, improve
      quality of life, and assure the earliest detection of breast cancer.

PMID- 14681957
TI  - Not all human cloning is alike.

PMID- 14681958
TI  - [Clinical and electromyographical analysis of peculiarities of parkinsonian
      syndrome in multiple system atrophy and Parkinson's disease].
AB  - Because differential diagnosis between Parkinson's disease (PD) and multiple
      system atrophy (MSA) may be difficult due to overlapping of clinical features,
      especially at the early stage of the diseases, a search for additional clinical
      and instrumental markers increasing reliability of etiological diagnosis appears
      actual. The article presents the results of comprehensive comparison of
      parkinsonian signs and spectral electromyography (sEMG) data in 18 patients with
      MSA, diagnosed clinically according to criteria of Gilman et al (1998), and in 21
      PD patients. Though no between-group differences in total expression of
      parkinsonian signs evaluated with The Unified Parkinson's Disease Rating Scale,
      part III, were found, MSA patients demonstrated progressive motor deficits,
      severer hypokinesia in the distal regions of the extremities, more pronounced
      impairment of axial movements, postural instability and gait disturbances but
      milder resting tremor, as compared to the PD patients (p < 0.05). Besides, the
      MSA patients were more frequently resistant to levodopa and had axial drug
      induced dyskinesia (p < 0.05). An analysis of sEMG data revealed that MSA
      patients had a more prominent peak in 10-17 Hz frequency band (for arm muscles)
      and in Hz 7-14 (for leg muscles) as well as higher amplitudes peak frequencies (p
      < 0.05) positively correlated to hypokinesia severity. The results may be useful
      for differential diagnosis between PD and MSA.

PMID- 14681959
TI  - [Cognitive disturbances in patients with tics and Tourette's syndrome and their
      correction with encephabol].
AB  - Ninety-four patients with tick hyperkinesis (57) and Tourette's syndrome (37)
      were studied. Neuropsychological examination revealed memory, attention and audio
      motor disturbances and symptoms of dysgraphia and dyslexia. Cognitive impairment
      may develop before ticks appearance and aggravate during hyperkinesis
      exacerbation. In the patients with Tourette's syndrome, cortical dysfunctions
      were mostly pronounced. These cognitive disturbances correlated with the indices
      of spectral analysis of bioelectrical brain activity in frontal and temporal
      areas. In 83 patients, an efficacy of encephabol treatment combined with basic
      therapy was studied. Encephabol given in dosage 200-300 mg daily to patients aged
      5-7 years and 600 mg--to those aged over 7 years during 6 weeks significantly
      improved memory, attention and praxis function.

PMID- 14681960
TI  - [Antihypertensive treatment with eprosartan mesilate of patients in acute and
      late periods of ischemic stroke].
AB  - Twenty patients with stroke of hemisphere localization developed as a result of
      arterial hypertension were treated with eprosartan mesilat. An estimation of the
      drug efficacy was conducted in comparison with other hypotensive medicines
      (control group). Eprosartan was used in dosage 600 mg daily. The study was
      carried out during 12 months, along with a monitoring of the most relevant
      hemodynamic indices, evaluation of somatic and neurological state of the patients
      as well as of some neuropsychological functions and quality of life, statistical
      significance of the results being determined. Pronounced hypotensive effect of
      the drug was found both in acute and late periods of stroke. Eprosartan mesilat
      monotherapy was effective in 75% of the patients. The most important feature
      proved to be a decrease of arterial pressure variability from the first days of
      the treatment, less frequency of secondary strokes being detected as well.

PMID- 14681961
TI  - [Use of pronoran (piribedil) in Parkinson's disease: the results of a multicenter
      study].
AB  - The study of 99 patients has been conducted in 5 Russian centers. Pronoran
      ("Servier", France) combined with levodopa was used in dosage 50-150 mg daily
      during 6 months. The treatment was placebo-controlled. Significant differences (p
      < 0.001) between the study and control groups in expression of all main symptoms
      of the disease were found.

PMID- 14681963
TI  - [Detoxification in withdrawal state in methadone maintenance patients].
AB  - A comparative study of withdrawal states of 7 methadone maintenance patients and
      21 heroin addicts was carried out. The protracted and low predictable course of
      methadone withdrawal states, along with relatively high resistance to clonidine
      and other medications, was demonstrated. Similarity of mental disorders,
      including addictive personality disorders, was found in both groups of patients.

PMID- 14681964
TI  - [Bioelectrical activity of the brain in paroxysmal and chronic forms of primary
      headache].
AB  - Eighty-three patients suffering from primary headache (HA) were studied. Migraine
      was diagnosed in 52 (migraine with aura--8, migraine without aura--30,
      transformed migraine--14) and headache of tension--in 31 patients. EEG was
      registered before treatment, using evaluation by methods of visual and spectral
      analyses. The EEGs of all the patients were characterized by diffuse
      bioelectrical activity changes. In patients with headache of tension (episodic
      and chronic), the reduction of alpha rhythm with simultaneous increase of other
      frequency bands were the main EEG features. In migraine with- and without aura,
      EEGs were characterized by synchronization of alpha rhythm, its spatial
      redistribution and increased presentation of bilaterally synchronous alpha- and
      theta-activity. Comparing to EEGs in migraine with episodic attacks (migraine
      with- and without aura), those in transformed migraine distinguished
      significantly by decrease of alpha rhythm. Spectral analysis revealed an increase
      of spectral power of frontal regions in all forms of primary HA, a total increase
      of theta-band power in all forms of migraine and an increase of theta-band power
      in frontal regions in headache of tension. Migraine with- and without aura was
      characterized by reduction of alpha band power in occipito-parietal hemisphere
      regions.

PMID- 14681962
TI  - [Psychotropic drugs used in a psychiatric hospital (pharmaco-epidemiologic
      aspects)].
AB  - The aim of the study was to optimize psychopharmacotherapy in a big psychiatric
      hospital. It was conducted in Moscow Alekseev psychiatric hospital No 1, using a
      method of comparison of standard psychotropic treatment and medication strategy
      suggested by the expert group. An analysis of the treatment of 966 patients with
      different mental disorders revealed that 78.3% were in need of neuroleptic
      assignment that was in line with routine practice. The expert's conclusions were
      postulated as follows: a need in phenothyazines is significantly lower than that
      observed in practice. Xantens and tyoxantens (chlorprothixene, flupentixol,
      zuclopenthixol, zuclopenthixol decanoate, zuclopenthixol acetate), benzamides
      (sulpiride) and such atypical antipsychotics as risperidone, olanzapine and
      quentiapine are underused in the treatment. Comparing to usual practice, more
      patients (35.8%) need antidepressants treatment. Thymoleptics should be assigned
      in greater daily doses. Selective inhibitors of serotonin reuptake (paroxetine,
      fluoxetine, citalopram, sertraline), reversible MAO A inhibitors (pyrazidolum),
      "double-action" drugs (mirtazapine, milnacipran) are recommended for wider usage.
      Less patients (33.4%) are in need of tranquilizers, though a number of
      medications used is consistent with a recommended one. Normothymics may be
      assigned to essentially less part of the patients and 18% of them need nootropics
      that is consistent with routine practice.

PMID- 14681965
TI  - [Bioelectrical activity of the brain in parents of schizophrenics].
AB  - The peculiarities of brain electric activity in mentally normal parents of
      schizophrenics (52 subjects) as compared to the control group of mentally normal
      subjects without family history of manifest psychosis (22 subjects). In both
      groups, EEG spectral densities and auditory evoked potentials (AEP)
      characteristics were compared. The parents of schizophrenics appeared to differ
      from controls by decrease of N1 amplitude and prolongation of N2, P3 which was
      similar to that observed in patients with schizophrenia. The findings are
      discussed as evidence of heritability of deviations in cognitive processes.

PMID- 14681966
TI  - [Peculiarities of sporadic motor neuron disease associated with D90A and G12R
      mutations in Russian population].
AB  - Fifty-one blood samples of Russian patients with sporadic motor neuron disease
      were examined for mutations in Cu/Zn superoxide dismutase (SOD-1) gene. One
      female patient with amyotrophic lateral sclerosis (ALS) was heterozygous for G12R
      mutation. This patient suffered from ALS with cervical cord onset, pyramidal
      variant and fast progression. Mutation was also detected in her healthy son.
      Earlier, such mutation was described in 5 Italian patients with slow progressive
      ALS. Also, D90A SOD-1 gene associated haplotypes of the female ALS patients
      previously examined by the authors have been analyzed. A homozygous female
      patient with ALS was characterized by typical lumbar onset and extremely slow
      progression, as well as a female patient with heterozygous mutation and moderate
      progression carried so-called "Scandinavian" haplotype. To our knowledge, it is
      the first report on the finding of the haplotype considered as a "protective" one
      in the subjects heterozygous for D90A mutation with clinical symptoms of ALS.
      Mechanisms of "protective" influence of this haplotype on ALS course are not yet
      elucidated. Our finding suggests that the presence of "Scandinavian" haplotype
      does not completely protect from the disease development in patients exposed to
      other more pathogenic causative factors. This assumption is in line with modern
      conceptions on motor neuron disease as a complicated multifactor disorder.

PMID- 14681967
TI  - [Polymorphism of serotonin receptor gene 5-HTR2A and schizotypic traits in
      mentally healthy subjects].
AB  - Serotonin receptor type 2 (5-HTR2A) polymorphism was consistently reported to be
      related to schizophrenia and some clinical presentations of the disease. The
      present study aimed at searching for association between 5-HTR2A polymorphism and
      schizotypic personality traits being considered as recognized phenotype
      predisposing to schizophrenia. Relationship between these features measured by
      SPQ-74 and two 5-HTR2A polymorphic loci has been studied in mentally healthy
      community sample (n = 64). Significant difference was found between AG and GG
      genotype carriers on No-close-friends scale (t = 2.3; p = 0.03), with GG scoring
      higher on this item. Also, a trend towards higher scores on this scale (p = 0.08)
      was observed in women, but not in men, with A2A2 genotype. To a certain extent,
      the results confirm a hypothesis articulated in the study of G-allele and A2
      allele relation to interpersonal relationship factor of SPQ-74.

PMID- 14681968
TI  - [Effectiveness of the use of local chondro-protector in the treatment of
      vertebrogenic muscular pain].

PMID- 14681969
TI  - [Effects of cerebrolysin on trace element homeostasis in the brain].

PMID- 14681970
TI  - [The appearance of metabolic syndrome in treatment with atypical antipsychotics].

PMID- 14681971
TI  - [Structure, function and the role of factor XIII in human pathology].
AB  - Modern views on the functioning of coagulation system are constantly replenished
      with the facts obtained using the newest methods of molecular biology and
      medicine. The purpose of many components of this system is non-uniform and covers
      the whole spectrum of biochemical reactions responsible for homeostasis. Current
      data on one of such components--the factor XIII (fibrin stabilizing factor) are
      stated. Except for the description of the enzyme structure and functions,
      information is presented about the methods of its detection, which development
      has resulted in accumulation of knowledge on the role of fibrin stabilizing
      factor in bleedings and thrombosis genesis. Data are given on hereditary and
      acquired deficiency of the factor XIII, as well as on conditions accompanied with
      the increase of its activity.

PMID- 14681972
TI  - [Metallothioneins: the structure and mechanisms of action].
AB  - Metallothioneins (MT)--4 groups (MT-I, II, III and IV) of low molecular mass
      (approximately 6.5 kDa, 61-62 amino acid residues) cytosol proteins. They are
      rich in sulphur--20 residues for cysteine, are found in cytosol and nuclei of
      eucaryotic cells. MT-I and MT-II are found in all animal tissues, MT-III and MT
      IV--in the brain. The functions of MT are regulation and control of redox
      homeostasis, thioldisulphide equilibrium in the cell in synergism with GSH. MT
      molecule involve two domains, alpha and beta. MT gene promoter have response
      elements to metals (MRE), to glucocorticoids (GRE) and to oxidative agents,
      electrophilic compounds and xenobiotics (ARE). Expression and synthesis of MT are
      induced for heavy metals (Zn, Cu, Cd and so Hg, Pb, As, Ni, Ag a.o.);
      glucocorticoids and other stress-hormones and cytokines; free radicals,
      peroxides, cancerogens and antitumor drugs, UV and ionizing radiation. Zn and
      partially Cu are physiological inductors of MT. Other inductors act more or less
      actively as stress-agents. Zinc stabilizes MT molecule, enhances some of their
      functional activities as a scavenger of metal ions, of free radicals, toxins and
      xenobiotics. MT are exceptional protection agents for embryo and adult from Cd
      and other heavy metals, from ionizing radiation, cancerogens, alkylating and DNA
      linked agents, from oxidative stress. MT realizes negative control of immune
      system functions, of transcription factor NF-kB activity. The use of genetic
      engineering achievements (transgenic mice with defective MTF-1-genes and MT
      overexpressing genes) enlarge the possibilities of MT study and application.

PMID- 14681973
TI  - [Structuring of recognizing elements of biosensors. Genetic constructs for the
      directed immobilization and combination of recognizing and signal generating
      structures].
AB  - Data about the genetic-engineering approaches for providing of directed
      immobilisation of biological molecules on the transducer surface and for indirect
      revealing the formed specific complexes are analysed in this review. Creation of
      nanostructures on the transducer surface and a possibility to do directed
      transfer of biological molecules from one surface on the other one are considered
      as well.

PMID- 14681974
TI  - [Effect of aminotriazole on the activity of catalase and glucose-6-phosphate
      dehydrogenase in tissues of two frog species--Rana ridibunda and Rana esculenta].
AB  - Changes of the activity of catalase and glucose-6-phosphate dehydrogenase (G6PDH)
      during 48 hrs after intraperitoneal injection of 1.0, 0.5 and 0.1 mg
      aminotriazole per gram of body weight of two frog species as well as catalase
      inhibition by aminotriazole in vitro were investigated. Both aminotriazole
      concentration and species affiliation affected the catalase inhibition. The
      sensitivity of catalase from different tissues was decreased in the order: liver-
      kidney--lung--muscle--brain. The constant of half inhibition of lung catalase was
      significantly lower than that of liver and kidney catalase. The activity of G6PDH
      of AMT-treated frogs R. esculenta was higher comparing to control group. Possible
      ways of compensation of antioxidant defense under catalase inhibition are
      discussed.

PMID- 14681975
TI  - [Effect of spermine on activity of purified Ca2+, Mg2+-ATPase from plasma
      membranes of myometrium cells].
AB  - Effect of endogenous polyamine spermine, a relaxant of smooth muscle, on the
      activity of myometrium cell plasma membrane Ca2+, Mg(2+)-ATPase was studied. It
      was observed a tendency to activation of enzyme at the spermine concentrations
      0.1-0.5 mM, the increase of the polyamine concentrations up to 10 mM inhibited.
      ATPase by 80% (I50 = 5.5 +/- 0.3 mM). Spermine inhibited enzyme decreasing its
      turnover rate and affinity for Ca2+. The ATPase affinity for Mg2+ increased in
      the presence of spermine. It was revealed, that the inhibitory effect of spermine
      is changed by the stimulatory effect under the increase of Ca2+ concentration (up
      to 2.6 microM), that correlates with the relaxing effect of this polyamine on the
      smooth muscle.

PMID- 14681976
TI  - [Effect of nitrite-anions on Ca2+ transport into the sarcolemma of myometrium].
AB  - The influence of nitrite-anions physiological concentration on Ca2+ input into
      vesicles was investigated when using the "outside-out" vesicles of myometrial
      plasmalemma and 45Ca2+. It was established that nitrite-anions increased Ca(2+)
      permeability of plasmalemma and increased the affinity of cation-transport
      system. The effects are probably connected with reversible modification of
      glutamate residues that bound and transported Ca2+ within the membrane. These
      findings showed that nitrite-anions are competitive activators of the passive
      calcium transport. On the other hand the decrease of Ca2+ affinity for the
      transport system under transmembrane proton scattering by the membrane, by rapid
      dissipation of transmembrane delta pH. It may be possible that the dissipation of
      transmembrane proton gradient changed the conformation of calcium transport
      system that calls the difference of kinetic mechanism of NO2- action in case of
      delta pH = 0 and delta pH = 1.5 on vesicle membranes.

PMID- 14681977
TI  - [Modelling of Mg2+, ATP-dependent mitochondrial Ca ions transport in smooth
      muscle cells using protonophore CCCP-sensitive fluorescent tetracycline].
AB  - Mg2+, ATP-dependent Ca2+ accumulation in the rat myometrial mitochondria was
      investigated in complex experiment using Ca2+ isotope (45Ca2+) and Ca(2+)
      sensitive label tetracycline. Monotonous increase of the fluorescence signal,
      insensitive to thapsigargin (100 nM) was observed with following establishing the
      stationary state of incubation at 2 min. which correlates with results obtained
      using isotope technique. Experiments with isotope label signify, that
      protonophore CCCP, ruthenium red and sodium azide, in concentration 1 microM, 10
      microM and 10 mM respectively, totally inhibits the accumulation of the Ca ions
      in mitochondria. At the same time, in conditions of Mg2+, ATP-dependent Ca2+
      accumulation modeling in these cellular structures, CCCP and sodium azide, used
      in the same concentration, diminished tetracycline fluorescence signal increase.
      In the same conditions, the introduction of the CCCP (1 mM) into the incubation
      medium at 75 sec. after initiation of the transport process induced reversible
      quenching of the tetracycline fluorescence signal to the level, observed in case
      of initial CCCP presence in the medium. According to data obtained in the
      experiment, using Ca2+ isotope, Ca(2+)-ionophore A-23187 induces both the
      reversible release of previously accumulated Ca ions, and cause reversible
      quenching of the tetracycline fluorescence signal to the level, observed in case
      of initial CCCP (1 mM) and sodium azide (10 mM) presence in the incubation
      medium. Conclusion was drawn that the thapsigargin-insensitive and CCCP, sodium
      azide and A-23187-sensitive tetracycline fluorescence increasing in case of
      modeling of Mg2+, ATP-dependent Ca2+ accumulation in myometrial mitochondria
      reflect the Ca2+ uniporter functioning in those subcellular structures.

PMID- 14681978
TI  - [Use of three-hybrid system to detect RNA-binding activity of alfalfa mosaic
      virus coat protein].
AB  - We used yeast three-hybrid system, for studying interaction of alfalfa mosaic
      virus coat protein AMVCP (AMVCP) with RNA4, which codes this protein. We have
      shown that AMVCP with high affinity is bound to plus-chain of RNA4 in vivo. The
      mutational analysis has shown, that the N-terminal part of AMVCP (aa 1 to 85)
      contains RNA-binding domain. C-terminal part of this protein (aa 86 to 221) does
      not participate in direct interaction with RNA4. However activity of the reporter
      gene LacZ, which codes beta-galactosidase, in case of interaction only N-terminal
      part of AMVCP is five times lower, in comparison with full-length hybrid protein,
      that confirms that the tertiary structure of full-length AMVCP is more favourable
      for interaction with RNA4.

PMID- 14681979
TI  - [Effect of N-stearoylethanolamine and ionizing radiation on lipid components of
      the liver and heart microsomes in rats].
AB  - The influence of irradiation and NSE on the microsomal lipid composition of the
      rat liver and heart was studied. It was shown, that radiation treatment in a dose
      of 2 Gy had not a significant affect on the heart phospholipid composition,
      whereas in the liver the amounts of the phosphatidylethnolamine and
      phosphatidylinositol were increased and the amounts of the phosphatidylcholine
      and sphyngomieline were decreased. NSE did not impact on these characteristics.
      The alterations of the plasmalogen/diacyl forms ratio of the PC and PE also took
      place only in the liver microsome. The analysis of the fatty acids esterified to
      phospholipids showed similar situation: the fatty acids of the heart microsome
      less were changed than those of the liver microsome undergo irradiation. The
      amount of arachidonic acid rise after the adding of NSE to rats. Investigation of
      the important component of biological membranes--cholesterol and its esters also
      showed that the liver tissue is more vulnerable to irradiation than the heart.
      NSE led to insignificant increase of the not esterified cholesterol in the liver.
      As a result of the present work we may conclude that the liver microsome is more
      vulnerable than the heart under X-ray radiation and NSE has protective effect in
      these conditions.

PMID- 14681980
TI  - [Ontogenic characteristics of lipid peroxidation and antioxidant system enzymes
      in the brain of geese].
AB  - Peculiarities of antioxidant homeostasis of geese brain tissue during
      embryogenesis and early postnatal period have been studied. It has been shown
      that the cerebrum and hindbrain tissues are characterized by a higher level of
      lipid peroxidation compared to liver. Main antioxidative enzymes' activity
      (superoxide dismutase, catalase, glutathione peroxidase) in the brain already
      reaches its maximum in the middle period of embryogenesis. We have found that
      brain tissues are characterized by a lower activity of intracellular enzymes
      (superoxide dismutase, catalase) but increased glutathione peroxidase activity as
      compared to liver. The rate of Fe2+ initialized lipid peroxidation and
      coefficient of antioxidative activity were used as a criterion for evaluation of
      antioxidative system's status. According to the dynamics of these factors the
      highest tension of antioxidative system in the brain appears in the period of the
      contour (28 days) and juvenile (49 days) feather formation.

PMID- 14681981
TI  - [Structural and functional state of microsomal membranes in the rat brain cortex
      during long-term ethanol consumption].
AB  - The range of the Na+, K(+)-ATPase functional stability in microsomal fraction of
      rat brain cortex under long-term chronic ethanol (15%, v/v) consumption was
      ascertained. The enzyme activity decreased only after 15 months of alcoholisation
      on the background of the stable structural membrane characteristics (on the basis
      of the intrinsic and 1-anilinonaphthalene-8-sulfonate fluorescence parameters)
      and SH-content in postmitochondrial supernatant. The cellular homeostatic
      mechanisms under ethanol effect are discussed.

PMID- 14681982
TI  - [Effect of the composition of branched chain amino acids, taurine, and tryptophan
      on the amino acid metabolism in experimental models of alcoholism].
AB  - Ethanol withdrawal after forced alcoholization of rats according to Majchrowicz
      led to the development of amino acid imbalance in the pool of free amino acids in
      the liver (increasing levels of alanine, aspartate, glutamate, glutamine and
      histidine, decreasing levels of glycine, lysine, threonine and taurine) and blood
      plasma (increasing levels of tyrosine and alanine, decreasing levels of most
      glycogen aminoacids, branched-chain aminoacids and Lys). Less profound changes
      were observed after prolonged alcohol intoxication (decreasing levels of alanine,
      ornitine, citrulline and increasing level of Glu in liver, increasing levels of
      sulfur-containing compounds, Asp and Lys in blood plasma). Amino acid mixture
      which contained branched-chain amino acids, taurine and tryptophan administered
      intragastrically was found to correct levels of sulfur-containing amino acids,
      threonine, lysine and isoleucine after ethanol withdrawal and to eliminate
      disorders in urea cycle, exchange of threonine, glycine and phenylalanine after
      prolonged alcohol intoxication.

PMID- 14681983
TI  - [Effect of caloric restricted diet on the liver microsomal monooxygenase system
      in rats of various ages].
AB  - Dietary restriction is the only known experimental method to extend lifespan in
      mammals, but the mechanisms of this phenomenon are still unknown. It is
      determined that the keeping of animals on the calorie restricted diet results in
      essential changes of a drug-metabolizing enzymes contents, that is also confirmed
      by the change of response of the enzyme system to thyroxine action. As a whole,
      the results obtained will be coordinated with the point of view, according to
      which the action mechanisms of the dietary restriction consist in considerable
      change of a wide spectrum of biochemical processes, including the change of the
      level of monooxygenase system functioning.

PMID- 14681985
TI  - [Phospholipid and cholesterol levels in the tumor cell plasma membranes with
      different sensitivity to doxorubicin].
AB  - The investigation is aimed to study qualitative and quantitative composition of
      phospholipids, cholesterol content and lipids unsaturation index in plasma
      membranes of Guerin's carcinoma cells sensitive or resistant to doxorubicin. The
      comparison of infrared spectra and phospholipids unsaturation index showed that
      the unsaturation level of fatty acids in plasma membrane from resistant cells was
      lower than that from sensitive carcinoma cells. 31P-NMR spectroscopy of plasma
      membranes phospholipids shows the increase of phosphatidylserine and
      sphingomyeline content in plasma membrane isolated from resistant tumor as
      compared with sensitive tumor. The levels of phosphatidylcholine and
      phosphatidylethanolamine were equal in drug-resistant and drug-sensitive
      carcinoma strains. Changes in plasma membrane from resistant cells result in
      elevation of plasma membrane microviscosity and phosphatidylserine level increase
      can suggest the activation of P-glycoprotein-mediated efflux of doxorubicin.

PMID- 14681984
TI  - [Effect of omega-3 polyunsaturated fatty acids on activity of glutathione
      dependent enzymes in the liver cytosol and blood erythrocytes in rats with
      experimental chronic bronchitis and in the norm].
AB  - The influence of omega-3 polyunsaturated fatty acids (omega-3 PUFA) on the
      activity of glutathione reductase, glutathione transferase and glutathione
      peroxidase in the liver cytosole and red blood cells of normal rats and animals
      with experimental chronic bronchitis. omega-3 PUFA ("Tekom" medication) activate
      glutathione reductase of liver cytosole and glutathionperoxidase in the red blood
      cells in rats. In the rats with chronic inflammatory process in bronchia omega-3
      PUFA corrects the glutathione-dependent systems of detoxication. Effects were
      more expressed in the liver cytosole in comparison with the red blood cells. The
      using of omega-3 PUFA as a means for treatment and prophylaxis was more effective
      than for treatment only.

PMID- 14681986
TI  - [Effect of cadmium chloride on polyphosphoinositides content in the rat liver and
      kidneys].
AB  - The influence of cadmium chloride on the content of some fractions of
      polyphosphoinositides in the liver and kidneys of rats has been investigated in
      the work. We have reported that a single administration of sublethal dose of
      cadmium chloride leads to the long-term elevation of the content of
      diacylglycerol, which is responsible for the activation of protein kinase C. The
      increase of triphosphoinositides fraction content may be connected with
      activation of phosphoinositid-3-kinase and with accumulation of
      phosphatidylinositol-3,4-diphosphate and phosphatidilinositol-3,4,5-triphosphate,
      which are known as activators of some protein kinase C isoforms and also play an
      important role in the mitogen-activated protein kinase signaling pathway. The
      lipids fractions content changes were similar in the liver and kidneys, but had
      different time of response.

PMID- 14681987
TI  - [Effect of nickel compounds on glutathione-dependent antioxidant system of pea
      and maize shoots].
AB  - Accumulation of Ni ions in vegetative bodies of 6- and 10-days shoots of peas and
      maize, as well as the influence of Ni compounds on accumulation of the
      glutathione reduced form and activity of glutathione-dependent antioxidant
      enzymes were investigated. It was established, that Ni accumulation by the root
      system of plants is carried more efficiently, than by leaves. The increase of
      concentration of these toxic cations in cultivation medium results in the
      decrease of the glutathione reduced form in vegetative bodies of plants. A
      general tendency to the increase of antioxidant enzymes activity is shown under
      the action of Ni compounds.

PMID- 14681988
TI  - [Analysis of dose-dependent antibody titration curves].
AB  - Several types of dose-response titration curves were considered. It was
      demonstrated that the use of the so-called coordinates of dilution suggested
      earlier by us allows one to analyze the titration curves, obtained either by
      ELISA, or by agglutination. Theoretical curves, obtained by the developed theory
      are very similar to those obtained in experiments. It was shown, that the
      analysis of the titration curves could give important information concerning
      antibody-blocking factors in titration sera or other samples of studied
      antibodies.

PMID- 14681989
TI  - [Role of the protein tyrosine phosphatase CD45 in signal transduction of
      hematopoietic cells].
AB  - This review deals with the analysis of modern literature about structure,
      catalytical activity, biological role and practical usage of protein tyrosine
      phosphatase CD45, which is widely distributed in the membranes of hematopoietic
      cells. The enzyme location makes it a highly sensitive test for estimation of
      development of such pathological states as immunological and neoplastic diseases,
      malignant tumors and transplantation responses of tissue tearing away. Unequal
      enzyme isoforms expressed in various leucocyte cell lines at different stages of
      development and differentiation are typical of those species. The existence of
      multiple isoforms is not used only to determine various cell lines, but also
      causes existence of variable adhesion requirements resulting in local restriction
      of activity and changes in the substrate binding. There is no doubt that
      definition of substrate molecules, influence of proteintyrosinephosphatase CD45
      translocation and regulation of its activity by other ligands are important
      questions. Solution of these problems will be useful for searching the
      correctional means of dysfunctions of the tissues, enriched with protein tyrosine
      phosphatase CD45.

PMID- 14681990
TI  - [Interrelation between thrombin structure and its stability].
AB  - Data concerning peculiarities of fermentative nature and structure of thrombin in
      water-salt solution have been generalized; regularities of stabilizing effect
      made on thrombin by various polyols and other substances have been analyzed. It
      has been shown that formation of thrombin optimum macrostructure is one of the
      methods of its stabilization. Presence of different dissolving additives changes
      this enzymes hydration and this affects its stability and activity. There exist
      some systems to stabilize thrombin solutions. The systems consist of various
      salts, low-molecular and high-molecular polyols, surfactants, protein chain,
      composition buffer, etc. It has been shown that optimal concentrations of
      polyols, buffer salts and surfactants, as well as protein interaction increase
      considerably thrombin stability, preserving secondary structure even under its
      low concentration in the solution.

PMID- 14681991
TI  - [Ca2+/H+ exchange through plasma membrane in the system of transport of calcium
      and hydrogen ions].
AB  - The survey is aimed to review the data from literature, concerning possible
      mechanisms of Ca2+ and H+ transport through the plasma membrane of a cells, and
      also possibility of existence of Ca2+/H(+)-exchange in the plasma membrane of the
      muscle cells. It is known that the modification of pHl (delta pH) also can
      influence the work of the contractile system of muscle cells, and the transition
      of Ca2+ through the plasma membrane of the cells. Thus, one can suppose a direct
      relation between Ca2+ and H+ transport, through Ca2+/H+ exchange, and indirect
      relation through connection with other systems of transport of both Ca2+ (Ca(2+)
      ATPase, Na+/Ca2+ exchange), and H+ (Na+/H(+)-exchange, H(+)-ATPase). For example
      it is shown, that the activator (inhibitor) of the Na+/H(+)-exchange through the
      plasma membrane of muscle cells, influence the work of the retractive system. And
      as is known, Ca2+ takes main part in involvement in the system excitation-
      contraction, and, thus, influencing the work of the Na+/H(+)-exchange, it is
      possible to regulate transport of Ca2+ through the plasma membrane of a muscle
      cell. The problem about a possibility of existence of Ca2+/H+ exchange, or
      functioning of Ca2+/H(+)-exchanger, is still far from the solution. Therefore, in
      the given review the attempt is made to analyze available information about
      possible connection between Ca2+ and H+ transport through the plasma cell
      membrane.

PMID- 14681992
TI  - [Biosynthesis of poppy isoquinoline alkaloids in nature and in vitro culture. 1.
      Opium poppy (Papaver somniferum L.)].
AB  - The analysis of literature data on production of isoquinoline alkaloids by
      Papaver somniferum L. plants and cell cultures has been made. The relationship of
      morphinane alkaloids biosynthesis with the processes of tissue and cell
      differentiation are discussed. The information on enzymes and pathways of
      regulation of morphine and sanguinarine biosynthesis are presented. The data on
      sanguinarine and morphine physiological role are analyzed.

PMID- 14681993
TI  - The influence of high ambient glucose level on the production of pericellular
      glycosaminoglycans by cultured endothelial cells.
AB  - The 14C-acetate metabolic labeling of glycosaminoglycans (GAGs) was used to
      investigate the effect of high glucose level on the production of hyaluronic acid
      (HA), heparan sulphate (HS), chondroitin sulphate (CS) and dermatan sulphate (DS)
      by human immortalized umbilical vein endothelial cells. It is demonstrated that
      30 mM glucose decreased the accumulation of HS and increased the accumulation of
      CS and DS in the cell layer, pericellular matrix and conditioned medium in 48 h
      of incubation. The modulation of the overall metabolism of sulphated GAGs by high
      glucose is in contrast to the observed redistribution of HA from the conditioned
      medium to the pericellular matrix of endothelial cells. The preincubation at 30
      mM glucose increased also the attachment of hyaluronidase-treated endothelial
      cells to HA-coated surface and had no effect on the cell attachment to poly-D
      lysine, indicating the alterations of CD44 binding to immobilized HA. The
      treatment of endothelial cells with p-nitrophenyl-beta-D-xylopyranoside, which
      inhibits the coupling of CS to the core protein, attenuated high glucose-induced
      pericellular HA accumulation and decreased cell attachment to HA-coated surface.
      It is supposed the implication of CD44-related CS in the accumulation of
      pericellular HA by endothelial cells exposed to high glucose level.

PMID- 14681994
TI  - [Thiamine triphosphatase activity in mammalian mitochondria].
AB  - Mitochondrial preparations isolated from bovine kidney and brain as well as the
      liver and the brain of rat show thiamine triphosphatase (ThTPase) activity. The
      activity was determined from the particles by freezing-thawing suggesting that a
      soluble enzyme is involved. The liberation patterns of ThTPase and marker enzyme
      activities from mitochondria under osmotic shock or treatment with increasing
      Triton X-100 concentrations indicate the presence of ThTPase both in the matrix
      and intermembrane space. It was found, basing on gel filtration behavior, that
      the mitochondrial ThTPase has the same molecular mass as specific cytosolic
      ThTPase (EC 3.6.1.28). The enzymes, however, were clearly distinguishable in Km
      values, the mitochondrial one showing a higher apparent affinity for substrate.
      These results imply the existence of ThTPase multiple forms in mammalian cells.

PMID- 14681995
TI  - [Role of ATP-sensitive potassium channel activators in liver mitochondrial
      function in rats with different resistance to hypoxia].
AB  - Effects of ATP-sensitive potassium (KATP) channels opener pinacidil (0.06 mg/kg)
      and inhibitor glibenclamide (1 mg/kg) in rats with different resistance to
      hypoxia on indices of ADP-stimulation of mitochondrial respiration by Chance,
      calcium capacity and processes of lipid peroxidation in liver has been
      investigated. We used next substrates of oxidation: 0.35 mM succinate, 1 mM alpha
      ketoglutarate. Additional analyses contain the next inhibitors: mitochondrial
      fermentative complex I-10 mkM rotenone, succinate dehydrogenase 2 mM malonic
      acid. It was shown that effects of pinacidil induced the increasing of oxidative
      phosporylation efficacy and ATP synthesis together with lowering of calcium
      capacity in rats with low resistance to hypoxia. Effects of pinacidil were
      leveled by glibenclamide. These changes are connected with the increasing of
      respiratory rate, calcium overload and intensification of lipid peroxidation
      processes. A conclusion was made about protective effect of pinacidil on
      mitochondrial functioning by economization of oxygen-dependent processes,
      adaptive potentialities of organisms with low resistance to hypoxia being
      increased.

PMID- 14681996
TI  - [Mechanisms of acetylcholine-dependent production of H2O2 and NO2- by stromal
      cells of endometrium].
AB  - The metabolism of NO(NO2-) and H2O2(O2-) by stroma cells of pig endometrium is
      NAD(P)H and glutathione-dependent process. The efficiency of biosynthesis and
      utilization of these metabolites appreciably depends on the state of SH-groups of
      the conforming ferment systems. And the reversible oxidation of SH-groups (maybe
      by the reaction products) results in the drop of biosynthesis rate. The NO and
      H2O2 metabolism is also defined by the state of oxidative metabolism of
      arachidonic acid (depending on salicylate), and also intensity of a course of
      redox-processes on plasmalemma (is regulated by cytochrome c). The NO2-
      biosynthesis by stroma cells is strongly inhibited by the agents, which super
      produce H2O2(O2-) (salicylate and cytochrome c). The NO(NO2-) and H2O2(O2-)
      metabolism at stimulation by acetylcholine is of cyclic character, and the
      infringement of any link during biosynthesis or utilization of these compositions
      results in losses of cyclicity. In contrast to this the formation of
      nitrosoglutathione with time achieves the saturation, which reflects its buffer
      and depositing with respect to NO function and permits to consider formation of
      the latter as one of mechanisms of effective utilization of NO(NO2-)--by the
      stroma cells.

PMID- 14681997
TI  - [Changes of nitric oxide level at different stages of primary open-angle
      glaucoma].
AB  - The contents of NO stable metabolites in tears, and blood serum of the patients
      with different stages of open-angle glaucoma have been studied. The increasing of
      NO stable metabolite contents was found in tears, aqueous humor and blood serum
      during glaucoma progression. The depletion of glaucoma pathogenesis oxidative
      link was found at the terminal stage of the disease. The results of our
      investigation are proposed to be used for glaucoma diagnostic.

PMID- 14681999
TI  - [Effect of fluoroaluminate on the ATP-hydrolysing and Ca2+-transporting activity
      of the purified Ca2+, Mg2+-ATPase of myometrium cell plasma membranes].
AB  - Fluoroaluminate, known modulator of G-proteins, inhibits ATP-hydrolase activity
      of purified solubilized Ca2+, Mg(2+)-ATPase from myometrium cell plasma membranes
      and Ca(2+)-transporting activity of this enzyme reconstituted into azolectin
      liposomes: 10 mM NaF plus 10 microM AlCl3 inhibited the primary activity by 95%
      and--by 81%. Inhibition of purified both solubilized and reconstituted Ca2+,
      Mg(2+)-ATPases by fluoroaluminate evidences for the possibility of direct
      interaction AlF4- with this enzyme without involvement of G-protein. The
      sensitivity to fluoroaluminate of sarcolemmal Ca2+, Mg(2+)-ATPase from myometrium
      is similar to that of Ca2+, Mg(2+)-ATPase from stomach smooth muscle.

PMID- 14681998
TI  - [Effect of exogenous factors on metabolism of phosphorous compounds in the
      chicken tissues].
AB  - The activity of plant and microbic phytases depending on the medium pH was
      studied. The factors have been investigated as follows: decomposition efficiency
      of seed ingredients and the releasing of phytate phosphorus; the efficiency of
      the adsorption of phosphorus under the in situation of microbic phytase; the
      influence of microbic phytase feeding in the ratios with low content of
      accessible phosphorus for assimilation of phytate phosphorus and poultry
      production indices. It has been stated that the microbic phytase has a wider
      optimum of action depending on pH value. The microbic phytase positive action on
      the metabolism of phosphorus in the chicken organism has been determined through
      the experimental investigations.

PMID- 14682000
TI  - [Activity of the basic carboxypeptidases in female rat tissues at different
      stages of estrus cycle].
AB  - It is revealed, that the activity of neuropeptide metabolism enzymes
      (carboxypeptidase H, phenylmethylsulfonilfluorid-inhibited carboxypeptidase) in
      the female rat tissues depends upon the stage of estrus cycle. The
      carboxypeptidase H activity in the pituitary gland is the highest in proestrus;
      it is almost 3 times higher in comparison with diestrus; it is a little bit
      higher in striatum on the stage of estrus, than in diestrus and proestrus, in
      adrenals on the stage of proestrus and estrus it is a little bit lower, than in
      diestrus; in the ovaries on the stage of proestrus it is much higher, than in
      estrus and diestrus. The activity of PMSF-inhibited carboxypeptidase in ovaries
      on the stage of proestrus and diestrus is 1.7-1.8 times higher, than at the stage
      of diestrus. The activity of carboxypeptidase M in adrenal tissue at the stage of
      proestrus is 35-40% of that at the stage of diestrus and estrus. The activity of
      carboxypeptidase M in the ovaries at the stage of diestrus is 45-50% of that at
      the stage of diestrus and estrus. The role of the investigated enzymes in cyclic
      changes of a level of biologically active peptides and in regulation of estrus
      cycle is discussed.

PMID- 14682001
TI  - [Fatty acid composition of lipids in erythrocytes and blood plasma in cadmium
      intoxication and its correction with unitiol].
AB  - The effect of cadmium chloride on the fatty acid composition of lipids of the
      erythrocytes and blood plasma has been studied. It has been established that in
      the process of cadmium intoxication the decrease of the level of unsaturated
      fatty acids takes place and the most considerable changes in the content of oleic
      and arachidonic acids. It makes possible to assume the disturbance of both the
      erythrocytes membrane structure and metabolism in the erythrocyte. Unitiol
      injection promotes the normalisation of the indices under investigation.

PMID- 14682002
TI  - [Differentiation between arylsulfatase A deficiency and pseudo-deficiency].
AB  - Metachromatic leukodystrophy (MLD)--lysosomal storage disease caused
      arylsulfatase A (ARSA) deficiency. Biochemical diagnostic of MLD is complicated
      by arylsulfatase A pseudodeficiency. There is possibility of mistake in MLD
      diagnoses in case of pseudodeficiency ARSA and non-MLD neurological disease
      combination. We suggest the new modification of arylsulfatase A activity
      detection method which allows to identify the arylsulfatase A pseudodeficiency
      without molecular genetic methods.

PMID- 14682004
TI  - [The contribution of the Nobel laureates to biochemistry and molecular biology].
AB  - The Nobel Prize winners works are considered and analyzed. Main attention is paid
      to the works devoted to biochemistry or problems related to biochemistry. The
      most prominent biochemical investigations are considered in detail. In some cases
      it is given the history and chronology of important biochemical discoveries. The
      survey is devoted due to the 170th anniversary of birth of Alfred Bernhard Nobel-
      a famous scientist and businessman, the founder of the Nobel Prizes.

PMID- 14682005
TI  - [Pathology of the endometrium in breast cancer patients treated with tamoxifen
      (nolvadex)].
AB  - The objectives of this study were to: 1) characterize histologically endometrial
      biopsy findings for genital bleeding in breast cancer patients receiving
      Tamoxifen; 2) analyze histologically endometrial carcinoma in the same patients.
      We analyzed biopsy specimens divided into three groups: 1) 112 biopsies
      (curettages and hysterectomy specimens) from 88 breast cancer patients receiving
      Tamoxifen (Nolvadex): T+; 2) 27 biopsies (curettages and hysterectomy specimens)
      from 22 breast cancer patients not receiving Tamoxifen but biopsied for genital
      bleeding: T-; 3) 139 curettages control samples received for analysis in the
      period January-March 2000 from women with peri- and postmenopausal genital
      bleeding: K. The analysis was performed on archival H&E sections. The most
      frequent finding in breast cancer patients receiving Tamoxifen was endometrial
      polyp. Compared with the other two groups (T- and K) the frequency of this
      finding was statistically significant. No difference was found in the prevalence
      of endometrial cancer between the three groups. The analyzed endometrial
      carcinomas in Tamoxifen-treated breast cancer patients show signs, characteristic
      of Bochman type I: predominantly endometrioid, of low grade and FIGO stage, with
      good prognosis.

PMID- 14682006
TI  - [Cyproterone acetate improves beta-cell function in postmenopausal women with
      diabetes mellitus type 2].
AB  - Menopause is associated with two main risk factors for the development of type 2
      diabetes mellitus--impaired beta-cell insulin secretion and insulin resistance.
      Physiologically estrogens improve carbohydrate metabolism, but this is not the
      case with different progestogens. The aim of the present study was to evaluate
      the effect of Cyproterone acetate (a progestogen with antiandrogenic activity) on
      insulin secretion, peripheral insulin sensitivity, lipid parameters and
      parameters of oxidative stress. Seven type 2 diabetic females, of mean age 55.4
      +/- 4.7 years and mean BMI 30.8 +/- 9.39 kg/m2, in menopause for average 5 years,
      in good borderline glycaemic control (mean HbAic 7.8%), with dyslipidaemia,
      normal parameters of calcium and phosphate metabolism and with osteopenia (T
      score < 88%) were enrolled in the study. They were treated with Estradiol
      valerate + Cyproterone acetate (Climen, Schering) for three months. Phases of
      insulin secretion--first phase (FPIS), second phase (SPIS) and AUC for FPIS and
      SPIS were assessed during IVGTT. Insulin sensitivity was determined with the
      manual method of euglycaemic hyperinsulinaemic clamp technique. The
      postmenopausal diabetic women in the present study were with overweight and
      obesity; they did not increase their body weight during HRT and even decreased it
      by mean 0.7%. Insulin secretion improved after Climen--FPIS increased by 16% and
      SPIS by 44%. Insulin sensitivity increased by 15%; triglycerides decreased by 16%
      and HDL-cholesterol increased by 27%. Total antioxidant capacity of the serum
      (TAOK) increased by 7%. The favourable effect on the pathophysiological
      mechanisms improved metabolic control--HbAic was reduced by mean 3% after 3
      months. In conclusion, our results suggest that HRT with the progestogen
      Cyproterone acetate (Climen) should be preferred in postmenopausal type 2
      diabetic females with predominant beta-cell insulin secretion defect.

PMID- 14682007
TI  - [Prognostic value of some hormonal and ultrasound ovarian reserve tests].
AB  - OBJECTIVE: To determine the predictive value of basal estradiol, FSH and inhibin
      B levels, antral follicle count and mean ovarian diameter of ovarian response in
      controlled ovarian hyperstimulation (COH), in outcome with normal FSH
      concentration in early follicular phase of menstrual cycle. MATERIALS AND
      METHODS: Twenty nine patients undergoing IVF treatment. Blood samples were
      collected and transvaginal ultrasound was performed on early follicular phase of
      unstimulated cycle. Controlled ovarian hyperstimulation (COH) was performed on
      the base of long protocol. RESULT(S): Mean women age and basal FSH levels were
      significantly higher in cancelled cycles than in the control group, whereas basal
      inhibin B, mean ovarian diameter and antral follicle count was significantly
      higher in the latter. Mean basal E2 concentration was similar in both groups.
      CONCLUSION(S): In women with normal basal FSH level the determination of E2 has
      no prognostic value of poor response outcome. However, inhibin B, antral
      follicles count and mean ovarian diameter tests when applied separately are with
      good prognostic values.

PMID- 14682008
TI  - [Laparoscopy with low abdominal pressure].
AB  - The authors present their experience from operative laparoscopies performed with
      lower than usually accepted intaabdominal pressure.

PMID- 14682009
TI  - [Metastatic cancer in transposed ovaries after radical Wertheim-Meigs
      hysterectomy for a stage I B and II A cervical cancer].
AB  - In this research work we show our and foreign experience in preserving the
      ovarian function in young women and cervical cancer stage I B and II A. 6 cases
      are quoted for the period of time from 1987 till 2003 (4 patients with ovarian
      metastases from our experience and 2 patients with ovarian metastases found from
      the greek colleagues). Histologically 3 patients were with adenosquamous
      metastatic cervical cancers and 3 patients with squamous metastatic cervical
      cancers in the region of the transposed ovaries. The metastases occurred mostly 2
      to 3 years after the radical hysterectomies a modo Wertheim-Meigs. Nevertheless
      our experience which is connected with radical hysterectomies a modeo W. Meigs
      including both ovaries, we have also experience in transposing ovaries /one or
      both of them/. In some of them we found metastases. In our research work we found
      4 cases with metastases in transposed ovaries. In these cases a chemotherapy was
      applied: mitomicin C, etoposide, and cysplatinum. The greek colleagues also have
      applied such schemes of chemotherapy. 3 from the patients had a very good effect
      from the chemotherapy, in 2 the recurrences have appeared 2 years after the
      chemotherapy, and in one case there was a very big progression of the disease,
      nevertheless the chemotherapy. IT is very important for the oncogynaecologist to
      clear up if the transposition of the ovaries is safe and effective, especially in
      young patients with early cervical cancer receiving postoperative radiotherapy.
      That is why we did this research work in order to give more light on this
      problem.

PMID- 14682010
TI  - [Novel aspects of maternal-fetal relationships in preeclampsia].

PMID- 14682011
TI  - [Immune properties of breast milk].

PMID- 14682012
TI  - [Submucosal isthmicocervical myoma--problems of diagnosis, labor and puerperium].
AB  - A case of submucosal isthmicocervical myoma, 85 mm in diameter, diagnosed for
      first time during CS. The neonate is with atrophy of left m.
      sternocleidomastoideus and facial asymmetry due to impression in the left
      temporoparietal region, without neurological impairment. Multiple ultrasound
      examinations were done but the fibroids vas not diagnosed. During one examination
      we presume that the fibroid was mistaken for the head because the BPD was in
      great discrepancy with other ultrasound parameters of the fetus. During the
      operation OICC was not found that is why the dilatation was made through the
      vagina. A myomectomy was not made during the operation. Because of the pressure
      and the deformation of the cervical canal from the myoma a drain was inserted
      through the canal to facilitate the evacuation of the lochia. The post operative
      period passed without any complications, the drainage was taken off on the 7th
      post operative day and the patient was discharged on the 8th day.

PMID- 14682013
TI  - [Ovarian fibroma--a case report].
AB  - The ovarian fibroma is a rare benign tumor growing from the connective tissue of
      the ovarian cortex. The authors introduce a case with primary sterility and
      fibroma ovarii dextra. They discuss the etiology and diagnostic methods for this
      kind of tumor formation as well as the predictivity of the ultrasound
      examination.

PMID- 14682014
TI  - [Cervical cancer and pregnancy--diagnostic and therapeutic problems. Report of
      four cases and review of the literature].
AB  - In this publication are presented four cases of pregnant women with a cervical
      cancer (with preoperative staging) as follow: the first pregnant 6-7 g.w., stage
      T1a1, No, Mo, the second 19-20 g.w., staged as T2a, Nx, Mo; the third--in 20-21
      g.w., stage T1b2, Nx, Mo and the fourth in 29-30 g.w., with premature rupture of
      membranes and stage T1b2, Nx, Mo. To all patients was performed radical
      hysterectomy with pelvic lymphnode dissection, and to three of them followed by
      radiotherapy. To the first operation was performed after induced abortion, to the
      second hysterectomy was with a fetus in uterus, the third and fourth were with
      Sectio parva and Sectio caesarea, followed at the same time by radical
      hysterectomy. The different diagnostic and therapeutic approaches to pregnant
      women with a cervical cancer, depending of the stage of the disease, the term of
      pregnancy and the patient and physician's desire are discussed.

PMID- 14682015
TI  - [Effect and control of oral contraceptive Minesse (15 mkg EE/60 mkg Gestoden) on
      menstrual cycle and body weight].

PMID- 14682016
TI  - Nanocrystalline metals: another opportunity for medical devices?
AB  - Nanotechnology is everywhere and receiving massive investment. Many believe that
      the medical sector is going to be one of the major benefactors. This article
      addresses the opportunities with nanocrystalline metals.

PMID- 14682017
TI  - Capillary chip based characterisation of small tissue samples.
AB  - There is a clear need for cell- and tissue-based test systems for in vitro
      diagnostics and therapy evaluation. The advantages of tissue-based test systems
      are that the complex cell response is taken into account and that proteins are in
      their natural environment. The capillary measurement cell enables impedance
      measurement of small tissue samples with negligible electrode impedances and a
      high constant shunt resistance so that biologically relevant tissue parameters
      are determinable.

PMID- 14682018
TI  - Better by design: the humanising technology project.
AB  - This reports on a design initiative that is helping to translate some of the
      latest developments into commercial reality. Biosensor technology represents an
      immense opportunity to revolutionise diagnostics. Under this initiative, one
      company has developed a portable hand-held platform for rapid measurment of
      multiple diagnostic parameters.

PMID- 14682019
TI  - Efficient converting in advanced wound care.
AB  - The converting processes used in advanced wound care are typified by high waste,
      low machine utilisation and poor overall operating efficiency. This article looks
      at how to reduce waste, increase efficiency and ensure quality.

PMID- 14682020
TI  - Maximising tubing functionality, Part II: Processing guidelines.
AB  - Maximising tubing functionality requires a systematic approach and a basic
      understanding of the idiosyncrasies of polymer characteristics and morphology.
      The right selection of polymers is 50% of the solution with the remaining 50%
      found in the processing and handling stages of manufacture. Batch-to-batch
      variations in polymer MI is a given; the wisdom is to accept and deal with it
      intelligently.

PMID- 14682022
TI  - The IVD directive: late-phase practicalities.

PMID- 14682021
TI  - FDA pilot programme in support of global harmonisation.
AB  - Imagine having one document that would demostrate the conformity of a medical
      device with regualtory requirements worldwide. Although it may be some time
      before this goal is reached, the United States Food and Drug Administration is
      launching a premarket review pilot programme in support of  global harmonisation.
      This article discusses the programme and why European manufacturers should
      consider participating.

PMID- 14682023
TI  - Demystifying the standards process.

PMID- 14682024
TI  - Effective electromagnetic interference shielding for electronic equipment.
AB  - With the development of tough, durable compounds, plastics are the preferred
      material for electronic equipment housings. The availability of economical,
      effective coating materials that can give plastics some of the desirable
      properties lost in the switch from metals are helping to allow the design of
      reliable medical equipment.

PMID- 14682025
TI  - Medical devices in Israel today.
AB  - With an innovative industry and an active market, Israel is at the forefront of
      medical technology. The country follows international standards wherever possible
      and is a favourable location for clinical trials.

PMID- 14682026
TI  - Gifts to self and others.

PMID- 14682027
TI  - Physical symptoms comorbid with depression and the new antidepressant duloxetine.
AB  - Most general descriptions of depression that date back to Hippocrates, including
      the DSM-IV, have listed gastrointestinal problems, sleep disturbances, headaches,
      appetite changes, and aches and pains of a diffuse nature as common features of
      the disorder. In addition, physical symptoms have a strong association with
      psychiatric disorders, and the presence of any physical symptom may increase the
      likelihood of a mood or anxiety disorder by two-fold or three-fold. A growing
      body of evidence suggests that serotonin and norepinephrine may share
      neurochemical mechanisms that tie depression and physical symptoms together. Both
      selective serotonin reuptake inhibitors alone and antidepressant agents that
      incorporate both serotonin and norepinephrine reuptake inhibition have shown
      evidence of relieving physical symptoms. Given the additional disease burden
      caused by physical symptoms in depression, it is vital that antidepressant agents
      that effectively treat the physical symptoms and chronic pain associated with
      depression be used.

PMID- 14682028
TI  - Current treatment of generalized anxiety disorder.
AB  - Generalized anxiety disorder is the most common anxiety disorder and is second
      only to depression as the most common disorder diagnosed in primary care. Because
      it is potentially disabling due to its high comorbidity with other psychiatric
      conditions, psychiatric nurses must accurately diagnose GAD and formulate
      individualized treatment plans that promote positive outcomes for clients with
      this disorder.

PMID- 14682029
TI  - Cognitive-behavioral therapy. Treating individuals with dual diagnoses.
AB  - Because deinstitutionalization of individuals with mental
      retardation/developmental disability and mental illness has become the standard
      of practice, many practitioners are now faced with the challenge of serving the
      needs of this specialized population. The existence of mental illness in
      individuals with mental retardation has been well established in the literature,
      but there are relatively few studies involving therapeutic interventions in this
      client population. However, there is a theoretical framework that guides practice
      and measures the effectiveness of interventions with this specialized population.
      This article presents a case study exploring the application of cognitive
      behavioral therapy to a client with mental retardation and mental illness. The
      theoretical framework, major concepts, and key assumptions of the theory will be
      reviewed, as well as treatment outcomes.

PMID- 14682031
TI  - EMTALA on-call coverage rule.

PMID- 14682030
TI  - The balancing act. Collaboration between frontline forensic staff and hospital
      administration.
AB  - 1. Flexibility, creativity, and consistency are critical characteristics for both
      frontline staff and administrators in the delivery of treatment and care for
      complex forensic patients who may be difficult to manage. 2. Through
      collaborative efforts and ongoing communication, plans can be identified and
      implemented that enhance patient and staff safety and facilitate positive
      behavioral and rehabilitation outcomes for patients. 3. Effective partnerships
      among frontline staff, administration, patients, their families, labor unions,
      and communities contribute significantly to the effective resolution of conflicts
      and dilemmas in the provision of holistic care to forensic patients.

PMID- 14682032
TI  - NECTAR for your health. Revamping U.S. medical research means unifying data.

PMID- 14682033
TI  - Uncertain threat. Does smallpox really spread that easily?

PMID- 14682035
TI  - Seeing single photons. A superconducting way to spot photons one by one.

PMID- 14682034
TI  - Aching atrophy. More than unpleasant, chronic pain shrinks the brain.

PMID- 14682037
TI  - Our growing, breathing galaxy.

PMID- 14682036
TI  - Supercharging protein manufacture. A career deviation leads to a dynamic approach
      to producing biotech drugs.

PMID- 14682038
TI  - Decoding schizophrenia.

PMID- 14682039
TI  - RFID. A key to automating everything.

PMID- 14682040
TI  - Atoms of space and time.

PMID- 14682041
TI  - Women and men at Catalhoyuk.

PMID- 14682043
TI  - The curious history of the first pocket calculator.

PMID- 14682042
TI  - Spring forward.

PMID- 14682045
TI  - Direct transformation of site-saturation libraries in Bacillus subtilis.

PMID- 14682044
TI  - Albumin depletion method for improved plasma glycoprotein analysis by two
      dimensional difference gel electrophoresis.

PMID- 14682046
TI  - Heparinase treatment of RNA before quantitative real-time RT-PCR.

PMID- 14682047
TI  - Unexpected sensitivity of synthetic Renilla luciferase control vectors to
      treatment with a cyclopentenone prostaglandin.

PMID- 14682049
TI  - It was twenty years ago today: a celebration of two decades of optical
      sectioning.

PMID- 14682048
TI  - Improved eukaryotic promoter-detection vector carrying two luciferase reporter
      genes.

PMID- 14682050
TI  - High-throughput generation of sequence indexes from T-DNA mutagenized Arabidopsis
      thaliana lines.
AB  - A pipeline has been created for the characterization of Arabidopsis thaliana
      mutants by generating flanking sequence tags (FSTs) and optimized for economic,
      high-throughput production. The GABI-Kat collection of T-DNA mutagenized A.
      thaliana plants was used as a source of independent transgenic lines. The
      pipeline included robotized extraction of genomic DNA in a 96-well format, an
      adapter-ligation PCR method for amplification of plant sequences adjacent to T
      DNA borders, automated purification and sequencing of PCR products, and
      computational trimming of the resulting sequence files. Data quality was
      significantly improved by (i) restriction digestion of the adaptor-ligation
      products to reduce trivial sequences caused by co-amplification of fragments
      derived from the free plasmid, and (ii) the design of the adaptor primers for the
      second amplification step to enhance selective generation of single PCR
      fragments, even from lines with multiple T-DNA insertions. Gel-purification was
      avoided by including these steps, the number of amplification reactions per line
      was reduced from four to three, and the percentage of lines that yielded at least
      one FST was increased from 66% to 86%. More than 58,000 FSTs have been submitted
      to GenBank and are available at http://www.mpiz-koeln.mpg.de/GABI-Kat/.

PMID- 14682051
TI  - Quantitative PCR genotyping assay for the Ts65Dn mouse model of Down syndrome.
AB  - The Ts65Dn mouse is a segmentally trisomic model for Down syndrome. Until now,
      Ts65Dn mice have been identified by the laborious methods of either chromosomal
      analysis of cultured peripheral lymphocytes or fluorescent in situ hybridization
      (FISH). We report here a quantitative PCR method for genotyping Ts65Dn mice, as
      well as a phenotypic description for visually preclassifying mice to be
      genotyped.

PMID- 14682052
TI  - Annealing control primer system for improving specificity of PCR amplification.
AB  - A novel primer designed to improve the specificity of PCR amplification, called
      the annealing control primer (ACP), comprises a tripartite structure with a
      polydeoxyinosine [poly(dI)] linker between the 3' end target core sequence and
      the 5' end nontarget universal sequence. We show that this ACP linker prevents
      annealing of the 5' end nontarget sequence to the template and facilitates primer
      hybridization at the 3' end to the target sequence at specific temperatures,
      resulting in a dramatic improvement of annealing specificity. The effect of this
      linker is demonstrated by the incorporation of ACP sequences as primers during
      the amplification of target nucleotide sequence and as hybridization probes in
      the genotyping of single nucleotide polymorphisms. This is the first report to
      show that a poly(dI) linker between two different sequences of ACP forms a bubble
      like structure and disrupts or destabilizes DNA duplex formation at certain
      annealing temperatures.

PMID- 14682053
TI  - Moderate degradation does not preclude microarray analysis of small amounts of
      RNA.
AB  - Gene expression analysis by microarrays using small amounts of RNA is becoming
      more and more popular against the background of advances and increasing
      importance of small-sample acquisition methods like laser microdissection
      techniques. The quality of RNA preparations from such samples constitutes a
      frequent issue in this context. The aim of this study was to assess the impact of
      different extents of RNA degradation on the expression profile of the samples. We
      induced RNA degradation in human tumor and healthy tissue samples by endogeneous
      ribonucleases. Next, we amplified 20 ng total RNA degraded to different extents
      by two rounds of in vitro transcription and analyzed them using Affymetrix
      oligonucleotide microarrays. Expression differences for some genes were
      independently confirmed by real-time quantitative PCR. Our results suggest that
      gene expression profiles obtained from partially degraded RNA samples with still
      visible ribosomal bands exhibit a high degree of similarity compared to intact
      samples and that RNA samples of suboptimal quality might therefore still lead to
      meaningful results if used carefully.

PMID- 14682054
TI  - Two-dimensional liquid chromatography protein expression mapping for differential
      proteomic analysis of normal and O157:H7 Escherichia coli.
AB  - A multidimensional chromatographic method has been applied for the differential
      analysis of proteins from different strains of Escherichia coli bacteria.
      Proteins are separated in the first dimension using chromatofocusing (CF) and
      further separated by nonporous reversed-phase high-performance liquid
      chromatography (NPS-RP-HPLC) in the second dimension. A 2-dimensional (2-D)
      expression map of bacterial protein content is created for virulent O157:H7 and
      nonvirulent E. coli strains depicting protein isoelectric point (pI) versus
      protein hydrophobicity. Differentially expressed proteins are further
      characterized using electrospray/ionization time-of-flight mass spectrometry (ESI
      TOF-MS) for intact protein molecular weight (MW) determination and matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) peptide mass fingerprinting for protein identification. Using this method, no
      significant differential protein expression is exhibited between the two O157:H7
      strains examined over a pH range of 4.0-7.0, and O157:H7 strains could be
      distinguished from nonvirulent E. coli. Several proteins differentially expressed
      between O157:H7 and nonvirulent E. coli are identified as potential markers for
      detection and treatment of O157:H7 infection.

PMID- 14682055
TI  - Software tool for automated processing of 13C labeling data from mass
      spectrometric spectra.

PMID- 14682056
TI  - Oligo Design: a computer program for development of probes for oligonucleotide
      microarrays.
AB  - Oligonucleotide microarrays have demonstrated potential for the analysis of gene
      expression, genotyping, and mutational analysis. Our work focuses primarily on
      the detection and identification of bacteria based on known short sequences of
      DNA. Oligo Design, the software described here, automates several design aspects
      that enable the improved selection of oligonucleotides for use with microarrays
      for these applications. Two major features of the program are: (i) a tiling
      algorithm for the design of short overlapping temperature-matched
      oligonucleotides of variable length, which are useful for the analysis of single
      nucleotide polymorphisms and (ii) a set of tools for the analysis of multiple
      alignments of gene families and related short DNA sequences, which allow for the
      identification of conserved DNA sequences for PCR primer selection and variable
      DNA sequences for the selection of unique probes for identification. Note that
      the program does not address the full genome perspective but, instead, is focused
      on the genetic analysis of short segments of DNA. The program is Internet-enabled
      and includes a built-in browser and the automated ability to download sequences
      from GenBank by specifying the GI number. The program also includes several
      utilities, including audio recital of a DNA sequence (useful for verifying
      sequences against a written document), a random sequence generator that provides
      insight into the relationship between melting temperature and GC content, and a
      PCR calculator.

PMID- 14682057
TI  - In silico study of breast cancer associated gene 3 using LION Target Engine and
      other tools.
AB  - Sequence analysis of individual targets is an important step in annotation and
      validation. As a test case, we investigated human breast cancer associated gene 3
      (BCA3) with LION Target Engine and with other bioinformatics tools. LION Target
      Engine confirmed that the BCA3 gene is located on 11p15.4 and that the two most
      likely splice variants (lacking exon 3 and exons 3 and 5, respectively) exist.
      Based on our manual curation of sequence data, it is proposed that an additional
      variant (missing only exon 5) published in a public sequence repository, is a
      prediction artifact. A significant number of new orthologs were also identified,
      and these were the basis for a high-quality protein secondary structure
      prediction. Moreover, our research confirmed several distinct functional domains
      as described in earlier reports. Sequence conservation from multiple sequence
      alignments, splice variant identification, secondary structure predictions, and
      predicted phosphorylation sites suggest that the removal of interaction sites
      through alternative splicing might play a modulatory role in BCA3. This in silico
      approach shows the depth and relevance of an analysis that can be accomplished by
      including a variety of publicly available tools with an integrated and
      customizable life science informatics platform.

PMID- 14682058
TI  - Unraveling the molecular components and genetic blueprints of stem cells.
AB  - Remarkable progress in stem cell biology research over the past few years has
      provoked a promise for the future of tissue regeneration and gene therapies; so
      much so, that the use of stem cells in clinical therapy seemed to be just around
      the corner. However, we now realize there is still a huge task before us to
      improve our understanding of the nature of stem cells before utilizing them to
      benefit human health. Stem cell behavior is determined by specific gene products;
      thus, unraveling the molecular components and genetic blueprints of stem cells
      will provide important insight into understanding stem cell properties. Here we
      summarize the research of various groups using microarray technology and other
      approaches to determine the gene expression profiles in stem cells, particularly
      in hematopoietic stem cells (HSCs). These works have, to a certain degree, helped
      to narrow down the candidate genes predominantly expressed in HSCs, revealed a
      list of stemness genes, and indirectly demonstrated the wide-open chromatin state
      of stem cells and, with it, the molecular basis of the multipotentiality of stem
      cells.

PMID- 14682059
TI  - The elements of stem cell self-renewal: a genetic perspective.
AB  - Every day, the body produces billions of new blood cells. Each of these is
      derived from a rare cell in the bone marrow called the hematopoietic stem cell
      (HSC). Because most mature blood cells have a limited lifespan, the ability of
      HSCs to self-renew and replenish the mature cell compartment is critical to
      sustaining life. While great progress has been made in isolating HSCs and
      defining their functional and phenotypic characteristics, the molecular
      mechanisms that regulate their self-renewal remain a mystery. Over the last few
      years, alterations in HSC frequency and self-renewal capacity in transgenic and
      knock-out mice have led to the identification of novel mediators of HSC
      homeostasis in vivo. These genetically modified mice have revealed that
      maintenance of survival, proliferation, quiescence, and normal telomere length
      all contribute to the self-renewal of HSCs. They also highlight the need to test
      in context of the normal microenvironment the role of signaling molecules such as
      Notch and Wnt, which have emerged recently as important regulators of HSC self
      renewal. The emerging picture these data provide of the regulation of self
      renewal in HSCs has provided a better understanding of the basic biology of stem
      cells and holds promise for designing strategies to improve bone marrow
      transplantation.

PMID- 14682060
TI  - Hematopoietic cells from mice that are deficient in both Bcrp1/Abcg2 and Mdr1a/1b
      develop normally but are sensitized to mitoxantrone.
AB  - Hematopoietic stem cells (HSCs) express Mdr1a/1b and Bcrp1/Abcg2, which are
      members of the ATP binding cassette transporter family. Mice lacking both Mdr1
      type genes (Mdr1a and Mdr1b) or Bcrp1 had normal hematopoietic development, but
      it has been unclear whether Mdr1a/1b and Bcrp1 play redundant roles in
      hematopoiesis. We generated a mouse model lacking both Mdr1a/1b and Bcrp1
      expression (M-/-B-/-). The M-/-B-/- mice had normal numbers of peripheral blood
      cells, bone marrow colony-forming cells (CFCs) and colony-forming units-spleen
      (CFU-S), and demonstrated normal hematopoietic development. There was a near
      total elimination of side population (SP) cells in the bone marrow of M-/-B-/-
      mice compared to M+/+B-/- mice, primarily in the subpopulation lacking other HSC
      markers, which indicated that Mdr1a/1b was responsible for a small portion of SP
      cells that were mainly mature cells. Hematopoietic progenitor cells from the bone
      marrow of M-/-B-/- mice were more sensitive to mitoxantrone in vitro compared to
      either M-/-B+/+ or M+/+B-/- mice, suggesting that Mdr1a/1b and Bcrp1 may provide
      additive protection to HSCs against genotoxic agents. These studies demonstrate
      the lack of functional redundancy between these transporters for HSC development
      and further clarify their contributing role to the SP phenotype in HSCs and to
      intrinsic drug resistance within hematopoietic progenitor cells.

PMID- 14682061
TI  - Mouse and human embryonic stem cell models of hematopoiesis: past, present, and
      future.
AB  - Human embryonic stem (ES) cells provide a unique model and an important resource
      to analyze early hematopoietic development. Other systems to study mammalian
      hematopoiesis include mouse ES cells, dissection of timed mouse embryos, or use
      of human postnatal hematopoietic tissue typically isolated from bone marrow or
      umbilical cord blood. All these models have particular strengths and weaknesses.
      The extensive studies on murine hematopoiesis provide a basis for work on the
      human developmental system. Since there are likely some important species
      differences, use of human ES cells now provides an optimal means to evaluate
      basic cellular and molecular mechanisms that regulate the beginning stages of
      human blood development, prior to derivation of hematopoietic stem cells (HSCs).
      Eventually, research on human ES cells may provide an alternative source of HSCs
      and other blood products for hematopoietic cell transplantation or other cellular
      therapies.

PMID- 14682062
TI  - Immune-deficient mouse models for analysis of human stem cells.
AB  - The field of murine models of xenotransplantation has grown immensely over the
      past two decades. The explosive growth in this field is in part due to the fact
      that good in vitro methods do not exist yet to allow examination of human stem
      cell homing into the bone marrow compartment versus other tissues, long-term
      survival of human stem cells, or differentiation into tissues outside of the
      hematopoietic system. Since these important aspects of human stem cell biology
      can be examined in vivo using immune-deficient mice, the number of different
      strains and models is constantly increasing. The current review discusses the
      merits and drawbacks of each immune-deficient mouse xenograft system as it stands
      to date and reviews how each immune-deficient mouse model has been used to
      further our knowledge of human hematopoietic stem cell biology.

PMID- 14682063
TI  - Future challenges for hematopoietic stem cell research.
AB  - This perspective summarizes several important advances in hematopoietic stem cell
      (HSC) biology in the past few years and places these advances in the context of
      future directions in stem cell research. The potential utility of stem cells for
      gene therapy, tissue engineering, and the treatment of neurological and other
      forms of disease is simply too significant to ignore, and yet our knowledge and
      ability to deliver these forms of therapy in a safe and efficacious manner will
      require additional advances in the understanding of the basic biology of stem
      cells.

PMID- 14682064
TI  - Layered expression scanning: multiplex analysis of RNA and protein gels.
AB  - Northern blots and immunoblots are utilized in laboratories worldwide and offer
      several important features for analyzing mRNA and protein expression, including
      accuracy, low cost, evaluation of probe specificity, and information on
      transcript and protein forms based on molecular size. However, standard blotting
      techniques are hampered by three factors. They require a significant amount of
      input material, are laborious, and are capable of measuring only one protein or
      transcript at a time. Here we describe a simple yet effective technique for the
      multiplex analysis of standard RNA and protein gels using the layered expression
      scanning platform. The method relies on a novel membrane with high-affinity low
      capacity binding characteristics. Using this approach, multiple blots from an RNA
      or protein electrophoresis gel can be simultaneously produced. We believe this
      method will be widely applicable to expression studies for a broad range of
      biological systems.

PMID- 14682067
TI  - The politics of invisibility: HIV-positive women who have sex with women and
      their struggle for support.
AB  - HIV-positive women who have sex with women (WSW) have been routinely overlooked
      by government researchers, health care providers, and the AIDS service community.
      In addition to stigmas against homosexuality and HIV in larger society, low
      income African American and Latina HIV-positive WSW in particular face culturally
      based stigmas and are disproportionately affected by poverty, drug addiction,
      homelessness, sex work, and abuse. By analyzing 16 intensive interviews with low
      income HIV-positive WSW of color, the author examined the physical, emotional,
      and psychological needs of this population and their methods of coping with HIV.
      Also examined were the participants' perceptions of available support networks,
      which were examined in order to raise awareness of the complex battle fought by
      these women against HIV and homophobia in the face of greater social, cultural,
      and economic strife.

PMID- 14682068
TI  - Perception of HIV and safer sexual behaviors among lesbians.
AB  - There is little data on female-to-female transmission of HIV. Some women who have
      sex with women (WSW) have other high-risk behaviors that could lead to HIV
      infection. The belief that WSW are at no risk may lead to unsafe sexual
      practices. In this study, a convenience sample of 78 women was surveyed in order
      to explore the perception of HIV risk among lesbians, their sexual behaviors, and
      their sources of information about safer sex. Fifty-three percent reported they
      were at low risk for contracting HIV. Women reported knowledge of barrier methods
      (89% to 99%) and no sex during menstruation (92%). However, 35% to 40% reported
      no knowledge of less common safer sex practices. Women reported their source of
      knowledge as media (36%), workshops (22%), and friends (12%). Eighty-five percent
      stated that their health care provider knew they were lesbian, but only 15%
      reported receiving safer sex education. Nurses and nurse practitioners are aptly
      poised to provide critical HIV education and health care for this population.

PMID- 14682066
TI  - Hard-to-reach providers: targeted HIV education by the national AIDS education
      and training centers.
AB  - A national system of AIDS Education and Training Centers (AETCs) has received
      federal funding since 1987 to provide education to health care personnel (HCP)
      about HIV infection. The purpose of this study is to describe how AETC program
      personnel define and recognize HCP who are hard to reach and educate about HIV
      and to clarify the issues that make providers hard to reach. Twenty-three
      semistructured telephone interviews were used to collect data from AETC faculty
      and staff. Respondents were asked to identify the types of HCP who are hard to
      reach and to discuss why they are hard to reach. Themes identified to establish
      which HCP are hard to reach include specific professional groups (especially
      physicians and dentists) as well as providers who treated less than 10 HIV
      infected clients and some HIV-expert clinicians. Themes identified to establish
      why they are hard to reach include convenience, isolation, and attitudes.
      Analysis posits that hard-to-reach HCP fall into identifiable categories:
      "already know the information," "don't know they don't know the information,"
      "don't think they need to know the information," or "don't want to know the
      information." Respondents also identified innovative ways to approach hard-to
      reach providers.

PMID- 14682069
TI  - The state of science: violence and HIV infection in women.
AB  - Violence and human immunodeficiency virus (HIV) are two critical public health
      problems affecting the lives of millions of women today. The purpose of this
      article is to review the state of science that exists in linking the phenomena of
      violence and HIV infection in women. The history and scope of violence and HIV
      infection is presented. Theoretical models for the phenomena of violence and
      abuse against women and HIV risk behavior reduction are explored. The literature
      review consists of 44 research articles that examine risk factors for violence
      and HIV, violence associated with HIV/AIDS disclosure, history of violence and
      HIV/AIDS, forced or coercive sex and HIV/AIDS, and violence associated with HIV
      self-protection conduct. Implications for nursing practice and nursing research
      are presented.

PMID- 14682070
TI  - Immune mechanisms in HIV infection.
AB  - Recent advances in immunobiology have led to a greater understanding of the
      healthy immune system and the complex pathogenesis of human immunodeficiency
      virus (HIV) infection. Knowledge of the mechanisms underlying the decrease in
      CD4+ T cells is rapidly evolving as a result of new assays, genetic advances, and
      recombinant DNA technologies. Studying the immune responses of long-term non
      progressors is also providing insight into the immunopathology of HIV. Trials
      using highly active antiretroviral therapy and immune modulators have shown that
      it may be possible to reverse damage to the immune system and increase CD4+ T
      cell numbers. Current and future findings might provide the knowledge necessary
      to identify effective HIV drugs and vaccines with acceptable toxicity profiles
      and to determine whether it will be possible to fully restore immune system
      function in patients with HIV disease.

PMID- 14682071
TI  - Immune restoration in patients with HIV infection: HAART and beyond.
AB  - Since the introduction of highly active antiretroviral therapy (HAART), there has
      been a dramatic decrease in HIV-related morbidity and mortality. Suppressing HIV
      replication by HAART can result in a restoration of the CD4+ T-cell count and,
      consequently, a diminished risk of opportunistic infections. However, the degree
      of immune restoration that can be achieved with HAART varies from patient to
      patient. It is often incomplete and can be poorest in those patients who, because
      of their very low CD4+ counts, need it the most. Additional approaches are needed
      to increase immune restoration still further. Structured treatment interruptions,
      therapeutic immunization, and recombinant interleukin-2 are three such options
      that are currently being investigated.

PMID- 14682072
TI  - Interleukin-2--where are we going?
AB  - We have seen many advances in treatment modalities for patients infected with
      HIV. Trying to improve the immune system of our patients is one of them. An
      interesting treatment being investigated for this purpose is the use of
      interleukin-2. Interleukin-2 has been used in many clinical trials and is being
      used in ongoing trials. The successes/limitations of these trials have given us
      much information. Is immune reconstitution aided by the use of interleukin-2?

PMID- 14682073
TI  - Management of adverse effects associated with the use of interleukin-2 in
      patients with HIV infection.
AB  - Therapy with interleukin-2 challenges both the patient and the clinic staff. Pre
      education and side effect management are crucial to the successful administration
      of each cycle of interleukin-2.

PMID- 14682074
TI  - To lie or not to lie: that is the question.

PMID- 14682075
TI  - Herpes research uncovers possible clue to AD.

PMID- 14682076
TI  - PET scan may offer tool for earlier diagnosis of AD.

PMID- 14682077
TI  - Genes that influence risk of AD may vary over a lifetime.

PMID- 14682079
TI  - Substance in blood may reflect progression of AD.

PMID- 14682078
TI  - FDA approves memantine drug for treating AD.

PMID- 14682080
TI  - Confused and disturbed behavior in the elderly following silent frontal lobe
      infarction.
AB  - It is unclear whether silent frontal lobe infarction is truly asymptomatic;
      frontal behavioral syndromes following strokes have rarely been reported. We
      studied 12 elderly patients with silent frontal lobe infarction who were
      exhibiting confused and disturbed behavior. Ten were male and two female; their
      ages ranged from 68 to 79 (mean 78). Three groups of symptom clusters emerged:
      changes in mood and emotional behavior, cognitive deterioration with minor
      psychiatric symptoms, and a confusional state. When related to the CT scan
      location, three regions were identified: predominantly orbitofrontal, deep white
      matter and caudate, and border-zones, respectively. These findings were related
      to what is known about the neuroanatomic location of the lesions and the role of
      the frontal subcortical circuitry in relation to behavior. The different
      manifestations could be explained by damage to the frontal lobe or interruption
      of the complex frontal subcortical circuits.

PMID- 14682081
TI  - Memory for emotional stimuli in patients with Alzheimer's disease.
AB  - Although a hallmark of Alzheimer's disease (AD) is memory impairment, there is
      speculation that recall may be enhanced when an emotional component is associated
      with an event. The current study aims to assess whether patients with AD would
      recall emotionally laden material better than neutral stimuli. DSM-IV-diagnosed
      AD patients with mild to moderate dementia, as well as groups of young and
      elderly healthy controls, participated in this study. All subjects were
      administered three word lists for three trials each. The words were positive,
      negative, or neutral in valence and matched for concreteness, emotionality, and
      pleasantness. As expected, the controls performed significantly better than the
      AD patients. Importantly, the pattern of recall for the emotions was different,
      such that both control groups recalled all emotions equally, whereas the AD
      patients recalled significantly more negative words than positive or neutral.
      These findings of improved immediate memory for emotional material in AD lends
      support to the notion that mnemonic functions are differentially affected in the
      disease.

PMID- 14682083
TI  - Effects on memory of verbal labeling for hand movements in persons with
      Alzheimer's disease.
AB  - This study examined 1) whether patients diagnosed with dementia of the Alzheimer
      type spontaneously form verbal labels to remember nonmeaningful sequences of hand
      movements, 2) whether an instruction for a verbal labeling (VL) strategy could
      enhance memory performance, and 3) whether a relationship exists between the
      memory span for hand movements and a score on the Mini-Mental State Examination
      (MMSE). Of 18 Alzheimer's patients, 16 did not use the VL strategy spontaneously.
      However, if instructed, 12 of these 16 were able to use the technique. Of these
      12, four were able to retain the strategy. There was a significant correlation
      only between the movement memory span and the MMSE. Meta-memory of VL seems
      independent of visuospatial memory and cognitive status.

PMID- 14682082
TI  - A look at deaths occurring in persons with dementia lost in the community.
AB  - The purpose of this study was to examine cause of death in persons with dementia
      (PWDs) who have become lost in the community. The study was a retrospective
      review of 93 US newspaper articles describing PWDs being found dead in the
      community after leaving their caregiving situations unattended. Of these PWDs, 87
      percent were found dead in natural, secluded, unpopulated areas, such as woods,
      fields, ditches, and bodies of water. They were generally found less than a mile
      from where they left, but often were not found for extended periods. Males and
      persons from community-based residential facilities appear to be at higher risk
      of dying after leaving unattended than females and those living at home.

PMID- 14682084
TI  - Effects of animal-assisted therapy on agitated behaviors and social interactions
      of older adults with dementia.
AB  - The effects of a therapeutic recreation intervention using animal-assisted
      therapy (AAT) on the agitated behaviors and social interactions of older adults
      with dementia were examined using the Cohen-Mansfield Agitation Inventory and the
      Animal-Assisted Therapy Flow Sheet. In a pilot study, 15 nursing home residents
      with dementia participated in a daily AAT intervention for three weeks. Results
      showed statistically significant decreases in agitated behaviors and a
      statistically significant increase in social interaction pretest to post-test.

PMID- 14682085
TI  - Exploring the meaning of everyday life, for those suffering from dementia.
AB  - Living with dementia means struggling to preserve a sense of self, to retain (and
      reevaluate) one's values in a new situation, and to search for a new way of life.
      This study explored the meaning of everyday life as expressed by 11 people
      suffering from dementia. Data were collected through interviews with people in
      the early stage of a diagnosed dementia disease. The findings indicate that many
      people with dementia feel shame, sorrow, and sadness when their life with the
      disease begins but also indicate prospects of a more manageable life. Since the
      reaction and adjustment to dementia differs from person to person, professional
      caregivers need to use a case-specific approach in the provision of care.

PMID- 14682086
TI  - Caregiver attribution and resentment in dementia care.
AB  - The caregivers of 37 patients with a dementing illness completed rating scales
      regarding the frequency and severity of their care recipient's general behavioral
      disturbance and manipulative behaviors, as well as their own resentment and
      depression. Caregivers were randomized to a four-week psychoeducational group
      intervention or control group to investigate the effect of dementia caregiving
      education on the caregiving experience. Findings indicated that, while care
      recipient behavioral disturbance was correlated with caregiver resentment and
      depression, the primary relationship was between behaviors perceived by the
      caregiver as manipulative or willful and caregiver resentment and depression. We
      found no significant differences in caregiver attribution, resentment, or
      depression between the caregivers who participated in the group session and those
      in the control group. The study supports the existence of resentment among
      dementia caregivers, and an important relationship between caregiving outcomes
      and attributions made by caregivers regarding their care recipients' actions.
      These results are discussed in relation to existing research on caregiver
      distress and intervention.

PMID- 14682087
TI  - Effect of respite care training on the knowledge, attitude, and self-esteem of
      volunteer providers.
AB  - This pilot study explored the effect that respite care training had on
      volunteers' knowledge about Alzheimer's disease (AD), their attitudes toward the
      cognitively impaired, and their self-esteem. Volunteer respite providers (n = 52)
      were recruited and participated in four different day (seven-hour) respite care
      training programs. The sample was predominantly female (85 percent) and white (90
      percent). Knowledge about AD increased significantly after respite training (p <
      .001), and attitudes toward someone who wanders were also significantly improved
      (p = .026). Overall, the findings support the immediate effectiveness of the
      respite training program.

PMID- 14682088
TI  - Data interpretation hinges on the rationale for benchmarking project.
AB  - The size of the gap between performance and benchmark is a key guidepost.
      Balancing cost, quality, and speed aspects are at the heart of benchmarking. Just
      because data are less than perfect doesn't mean they should be discarded.

PMID- 14682089
TI  - SSM slashes LOS almost 2 days in just 2 weeks.
AB  - Case management is promoted as a service to physicians. Inflated costs and poor
      patient flow stir management to action. Two internal teams meet daily to discuss
      length-of-stay triggers.

PMID- 14682090
TI  - Patient flow product taps hidden capacity.
AB  - Significant revenue opportunities and reduced cost per case are possible.
      Methodology focuses on creating new measures of effectiveness for key factors.
      People, process, and tools addressed to drive culture change.

PMID- 14682091
TI  - Fundraising software bolsters efficiency.
AB  - Donors can be selected by parameters, including areas of interest and history of
      giving. Appeals become more effective because the right people are approached.
      Database frees up staff time to ensure timely, consistent follow-up.

PMID- 14682092
TI  - Driving mister dement. A primary care toolbox to evaluate older drivers.

PMID- 14682093
TI  - Skin redness following minimal sun exposure. Immediate erythema and edema appear
      at sites unprotected by clothing.

PMID- 14682094
TI  - Assessment and counseling of older drivers. A guide for primary care physicians.
AB  - Despite the proliferation of motor vehicles and the increase in number of miles
      traveled in this country during the past century, motor vehicle safety has
      improved. The annual death rate has declined dramatically since it was first
      measured in 1925. However, motor vehicle accidents remain the leading cause of
      injury death in children and young and middle-aged adults and the third leading
      cause of years of potential life lost prior to age 65, behind cancer and heart
      disease. There are some regional and vehicular factors, with higher motor vehicle
      death rates in the southeast and in scattered western states. The highest rates
      of vehicular fatalities are in the youngest and oldest drivers, their passengers,
      and in all who drive under the influence of alcohol or as a passenger in a car
      driven by someone under the influence. Medical conditions may also compromise
      driving ability and/or increase fatality rate in adults of all ages. These
      conditions and situations, particularly as applied to older adults, are presented
      here.

PMID- 14682095
TI  - Patient handout. The heart truth for women. What women need to know about heart
      disease.

PMID- 14682096
TI  - Heart disease in older women. Gender differences affect diagnosis and treatment.
AB  - Cardiovascular disease continues to be the leading cause of death in women over
      age 50 in the United States. Significant differences exist between men and women
      in the prevalence, incidence, and treatment outcomes of cardiovascular disease,
      particularly coronary artery disease. The presenting features of coronary artery
      disease may very between men and women, and the diagnostic evaluations of such
      symptoms may differ based solely on gender. Outcomes of angioplasty and bypass
      surgery, although not as extensively studied in women as in men, may be less
      favorable. The impact of risk factor modification may also differ due to the
      effects of menopause on cardiovascular events. More studies of cardiovascular
      outcomes In women are required, particularly now that hormone replacement therapy
      has been shown to increase cardiovascular event rates in most of the recent
      trials. Until such studies are available, our focus should therefore remain on
      treatment of risk factors where such treatment has clearly been shown to impact
      favorably on cardiovascular morbidity and mortality.

PMID- 14682097
TI  - Integrating technology and psychiatric care. Coming attractions.

PMID- 14682099
TI  - She said, "some patient needs get dropped due to more pressing issues".
AB  - The engagement of the social sciences by pastoral care and education will not
      turn chaplains or supervisors into social scientists. Ministry is not a higher
      calling than science; nor will chaplains be co-oped into doing ministry by the
      numbers. Scientific research in pastoral care and teaching could focus on these
      broad areas, but administrators face multiple pressures and will not easily be
      convinced by rational argument. As religion and science dare to engage a
      meaningful dialogue; a deeper, transcendent reality will unfold.

PMID- 14682100
TI  - Respecting the dual sided identity of clinical pastoral education and
      professional chaplaincy: the phenomenological research model.
AB  - The question discussed in this volume opens a debate on what kind of scientific
      research model should be used by professional chaplaincy and Clinical Pastoral
      Education (CPE). The problem begins with the assumption that "becoming more
      scientific" means using the natural sciences approach employed by psychology; an
      approach unsuitable to account for factors relative to faith, spiritual and
      religious issues. I argue that CPE and professional chaplaincy need to be more
      scientific but not necessarily under the natural sciences model. Considering the
      predominance of that model in psychology, I believe pastors and chaplains should
      resist pressures to rely on the natural science model and adopt instead models
      that respect their dual sided identity. I conclude by suggesting that the
      phenomenological research model best allows investigation of patients' spiritual
      as well as psychological issues.

PMID- 14682101
TI  - The search for truth: the case for evidence based chaplaincy.
AB  - Chaplaincy and medical science are in search of truth. Should chaplaincy become
      more scientific in response to health care reform? Yes is the answer. Chaplaincy
      ought to become more based in evidence for the following reasons. First, the
      health care culture is evidence based and chaplaincy needs to speak that
      language. Second, chaplaincy and science are not opposed. Third, tradition-driven
      chaplaincy already utilizes medical evidence. Fourth, spirituality is the domain
      of chaplaincy and other health care disciplines have provided the research in our
      domain. However, if chaplaincy becomes more scientific, it does not mean that
      chaplaincy will maintain or grow in its position in health care reform. Health
      care reform in relation to chaplaincy is driven more by values than evidence.

PMID- 14682102
TI  - Health care reform: opportunities for professional chaplains to build intentional
      communities of learners by integrating faith, science, quality, and systems
      thinking.
AB  - Albert Einstein once said, "The significant problems we face cannot be solved at
      the same level of thinking we were at when we created them"
      (www.brainyquote.com). Health care reform has brought professional chaplains to a
      place of chaos-a place that raises many questions about the past, present and
      future. This chaos presents tremendous opportunities for professional chaplains
      to increase their capacities in building intentional communities of learners by
      integrating faith, science, quality and systems thinking. Pastoral care givers
      must truly understand the pressures from all sides and the new emerging paradigm
      of integrated health care delivery. Without this understanding, we will not see
      the opportunities and challenges of integrating pastoral and spiritual care in
      the emerging structures and systems. The future of chaplaincy largely will depend
      on the quality of the data, quality of our conversations and our ability to
      thinking together through dialogue.

PMID- 14682103
TI  - The chaplain as the complete philosopher.
AB  - This paper argues that professional chaplaincy must reflect an authentic
      understanding of the religion and science dialogue by drawing not simply on the
      popular culture's views but on the long traditions of serious scholarship and
      research that explores both these worlds. The author claims that what often
      passes as science is really scientism or technophilia and that such distortions
      should not be allowed to guide or define the chaplain's or the clinical
      educator's healthcare ministry. The chaplain, as a reflection of religion, is
      obligated to draw on all of humankind's projects of enquiry-science, art,
      humanities, theological and religious studies, ethics- and ought not become a
      captive of a Zeitgeist that invites idolatry either in the forms of scientism and
      technophilia or in the forms of provincial and superficial understandings of
      religion.

PMID- 14682104
TI  - Rediscovering mystery and wonder: toward a narrative-based perspective on
      chaplaincy.
AB  - Should chaplaincy be scientific? The answer is a resounding yes! Science is not
      the enemy of chaplaincy any more than it is the enemy of theology. It is
      necessary and therapeutically vital that chaplains strive to base their theory
      and practice on appropriate and well-researched evidence. The substantial
      question, however, is: What actually constitutes acceptable evidence, who decides
      and why?

PMID- 14682105
TI  - Attention to the scientific benefits of pastoral care is a blessing and a curse.
AB  - The art of pastoral care may be difficult to describe but we know that the
      ability to measure and describe the process of becoming a clinically trained,
      professional pastoral care provider is possible. Within the Association for
      Clinical Pastoral Education we have developed standards that spell out the
      competencies needed to complete the desired skill outcomes. Instead of diluting
      the meaning of pastoral care, this movement has strengthened the training, at
      least for many supervisors, students and seminaries. I argue that being able to
      understand with more precision what we do and how we do it could only enhance the
      practice of our art and the understanding by others of what that art might look
      like.

PMID- 14682106
TI  - Presentations from the Walter Reed Army Medical Center. Case 1: rectal carcinoma.

PMID- 14682107
TI  - An argument against routine use of radiotherapy for ductal carcinoma in situ.
AB  - Three prospective randomized trials have shown that postexcisional radiation
      therapy can reduce the relative risk of local recurrence by about 50% in
      conservatively treated patients with ductal carcinoma in situ (DCIS). In an era
      of evidence-based medicine, how then can one possibly take a stand against the
      routine use of radiation therapy after local excision? Surprisingly, the
      rationale is straightforward. In some low-risk DCIS patients, the costs may far
      outweigh the potential benefits. In spite of a relative 50% reduction in the
      probability of local recurrence, the absolute reduction may only be a few
      percentage points. In addition, the prospective trials focus on local recurrence
      as their primary end point because it is, by far, the most common untoward event
      following conservative treatment. Local recurrence is clearly important, but
      breast cancer-specific survival is, in fact, an even more important end point,
      and no trial in patients with DCIS has ever shown a survival benefit with the use
      of radiation. Moreover, radiation therapy is not without financial and physical
      cost. So, if there is no difference in breast cancer-specific survival regardless
      of the treatment and in some subgroups the absolute benefit from radiation
      therapy is extremely small, it seems reasonable to attempt to develop a system to
      select patients with DCIS who could be safely treated in the least aggressive
      way. The University of Southern California/Van Nuys Prognostic Index (USC/VNPI)
      uses five independent predictors of local recurrence to do exactly that. The
      combination of tumor size, margin width, nuclear grade, age, and the presence or
      absence of comedonecrosis can be used to identify subgroups of patients with an
      extremely low probability of developing a local recurrence after excision alone.
      When accurate measurements of tumor size cannot be made, margin width can be used
      as a surrogate parameter for the USC/VNPI. New oncoplastic techniques that allow
      more extensive excisions can be used to achieve both acceptable cosmesis and
      widely clear margins, helping to alleviate the need for radiation therapy in many
      cases.

PMID- 14682108
TI  - Ovarian tumors of low malignant potential.
AB  - Clinical and laboratory reports suggest that ovarian tumors of low malignant
      potential (LMP) represent a "grab bag" of tumors, with different etiologies,
      molecular biologies, and prognoses. As a result, data on incidence and prognosis
      may be quite unreliable. Diagnosis is best made on permanent section. Half of
      women under age 40 undergo conservative, fertility-sparing surgery when diagnosed
      with an ovarian tumor of LMP, but no adjuvant therapy has been shown to prolong
      survival in this population. In addition to the various controversies surrounding
      LMP tumors, this review will address prognostic markers, risk of malignant
      transformation, treatment of progressive disease, surveillance after conservative
      surgery, and future directions for research.

PMID- 14682109
TI  - Clinical trials referral resource. Current clinical trials of supportive
      care/palliative care.

PMID- 14682110
TI  - Hematopoietic management in oncology practice. Part 1. Myeloid growth factors.
AB  - Hematopoietic growth factors have transformed the practice of oncology. The two
      major factors in clinical use are recombinant human (rh) granulocyte colony
      stimulating factor (G-CSF, filgrastin [Neupogen]) and granulocyte-macrophage
      colony-stimulating factor (GM-CSF, sargramostim [Leukine]). These factors differ
      significantly in their role in hematopoiesis and the regulation of mature
      effector cell function. G-CSF regulates both basal and neutrophil production and
      increased production and release of neutrophils from the marrow in response to
      infection. GM-CSF mediates its effects on the neutrophil lineage through its
      effects on phagocytic accessory cells and its synergy with G-CSF, but it does not
      appear to have a role in basal hematopoiesis. Part 1 of this two-part series
      focuses on the use of the myeloid growth factors rhG-CSF and rhGM-CSF to shorten
      the duration of chemotherapy-induced neutropenia and thus prevent infection in
      cancer patients. In randomized trials, rhG-CSF has consistently decreased the
      duration of neutropenia during all cycles of chemotherapy and reduced the risk of
      infection by 50% or more. Trials of rhGM-CSF have not reported consistent
      results.

PMID- 14682111
TI  - Imatinib mesylate: a molecularly targeted therapy for gastrointestinal stromal
      tumors.
AB  - Although their overall incidence is uncommon, gastrointestinal stromal tumors
      (GIST) are the most frequently encountered mesenchymal tumors of the GI tract.
      Their pathology has been recently defined by the presence of KIT (transmembrane
      receptor tyrosine kinase). The majority of GISTs have c-kit gain-of-function
      mutations mainly in exon 11 (highly conserved juxtamembrane region) that
      eventuates in constitutive activation of KIT, promoting proliferation and
      antiapoptotic signaling. Imatinib mesylate (Gleevec) is a specific inhibitor of
      KIT kinase activation, and in phase II clinical trials has proven to be
      remarkably efficacious in heavily pretreated GIST patients with advanced disease.
      The molecular and genomic determinants of response/resistance patterns are the
      subject of ongoing studies, and adjuvant studies are also under way. The initial
      evaluations of imatinib provide proof of concept for the hypothesis-driven design
      of selective molecularly targeted therapies for solid tumor malignancies.

PMID- 14682112
TI  - Introduction. Neutropenia risk models in oncology.

PMID- 14682113
TI  - Risk assessment in oncology clinical practice. From risk factors to risk models.
AB  - Myelosuppression and neutropenia represent the major dose-limiting toxicity of
      cancer chemotherapy. Chemotherapy-induced neutropenia may be accompanied by
      fever, presumably due to life-threatening infection, which generally requires
      hospitalization for evaluation and treatment with empiric broad-spectrum
      antibiotics. The resulting febrile neutropenia is a major cause of the morbidity,
      mortality, and costs associated with the treatment of patients with cancer.
      Furthermore, the threat of febrile neutropenia often results in chemotherapy dose
      reductions and delays, which can compromise long-term clinical outcomes.
      Prophylactic colony-stimulating factor (CSF) has been shown to reduce the
      incidence, severity, and duration of neutropenia and its complications.
      Guidelines from the American Society of Clinical Oncology recommend the use of
      CSF on the basis of the myelosuppressive potential of the chemotherapy regimen.
      The challenge in ensuring the appropriate and cost-effective use of prophylactic
      CSF is to determine which patients would be most likely to benefit from it. A
      number of patient-, disease-, and treatment-related factors are associated with
      an increased risk of neutropenia and its complications. A number of clinical
      predictive models have been developed from retrospective datasets to identify
      patients at greater risk for neutropenia and its complications. Early studies
      have demonstrated the potential of such models to guide the targeted use of CSF
      to those patients who are most likely to benefit from the early use of these
      supportive agents. Additional prospective research is needed to develop more
      accurate and valid risk models and to evaluate the efficacy and cost
      effectiveness of model-targeted use of CSF in high-risk patients.

PMID- 14682114
TI  - Risk models for neutropenia in patients with breast cancer.
AB  - Breast cancer is the most common noncutaneous malignancy in women in
      industrialized countries. Chemotherapy prolongs survival in patients with early
      stage breast cancer, and maintaining the chemotherapy dose intensity is crucial
      for increasing overall survival. Many patients are, however, treated with less
      than the standard dose intensity because of neutropenia and its complications.
      Prophylactic colony-stimulating factor (CSF) reduces the incidence and duration
      of neutropenia, facilitating the delivery of the planned chemotherapy doses.
      Targeting CSF to only at-risk patients is cost-effective, and predictive models
      are being investigated and developed to make it possible for clinicians to
      identify patients who are at highest risk for neutropenic complications. Both
      conditional risk factors (e.g., the depth of the first-cycle absolute neutrophil
      count nadir) and unconditional risk factors (e.g., patient age, treatment
      regimen, and pretreatment blood cell counts) are predictors of neutropenic
      complications in early-stage breast cancer. Colony-stimulating factor targeted
      toward high-risk patients starting in the first cycle of chemotherapy may make it
      possible for full doses of chemotherapy to be administered, thereby maximizing
      patient benefit. Recent studies of dose-dense chemotherapy regimens with CSF
      support in early-stage breast cancer have shown improvements in disease-free and
      overall survival, with less hematologic toxicity than with conventional therapy.
      These findings could lead to changes in how early-stage breast cancer is managed.

PMID- 14682115
TI  - Risk models for chemotherapy-induced neutropenia in non-Hodgkin's lymphoma.
AB  - Non-Hodgkin's lymphoma is primarily a disease of the elderly, with 61% of the new
      cases reported in patients 60 years old or older. Aggressive combination
      chemotherapy can cure some patients, but there are frequently treatment failures
      and overall survival is low. Retrospective studies have found that treatment with
      less than standard chemotherapy doses is associated with lower survival, and
      surveys of practice patterns have found that many patients, especially elderly
      ones, are treated with substandard regimens and doses. Neutropenia is the major
      dose-limiting toxicity of chemotherapy in patients with non-Hodgkin's lymphoma.
      First-cycle use of colony-stimulating factor (CSF) can reduce the incidence of
      neutropenia and its complications and help maintain the chemotherapy doses.
      Researchers have investigated risk factors in patients with non-Hodgkin's
      lymphoma to determine which patients are at highest risk for neutropenia and
      would benefit from targeted first-cycle CSF support. It has been shown in several
      studies that advanced age, poor performance status, and high chemotherapy dose
      intensity are risk factors. Other trials suggest that low serum albumin levels,
      elevated lactate dehydrogenase levels, bone marrow involvement, and high levels
      of soluble tumor necrosis factor receptor are also risk factors. Dose intensity
      has also been shown in many studies to be an important predictor of survival in
      patients with non-Hodgkin's lymphoma. Managing the toxicity of chemotherapy with
      CSF has facilitated the delivery of planned dose on time, as well as dose
      intensified chemotherapy regimens. The promising results from recent clinical
      trials of dose-dense regimens with CSF support suggest that this could prove to
      be the best strategy for improving patient outcomes.

PMID- 14682116
TI  - Myelosuppression and its consequences in elderly patients with cancer.
AB  - Cancer is a disease of the elderly, and its incidence and mortality increase with
      age. The number of persons with cancer is expected to double between 2000 and
      2050, from 1.3 million to 2.6 million, with the elderly accounting for most of
      this increase. Studies have shown that otherwise-healthy older patients treated
      with chemotherapy of similar intensity obtain benefits comparable to those
      obtained by younger patients. However, chemotherapy-induced neutropenia and its
      complications are more likely in older patients; they are also more often
      hospitalized because of life-threatening infectious complications. Furthermore,
      most neutropenic episodes in elderly patients occur in the early cycles of
      chemotherapy. To minimize the occurrence of chemotherapy-induced neutropenia,
      older patients are often treated with less-aggressive chemotherapy and with dose
      reductions and delays, which may compromise treatment outcome. The proactive
      management of myelosuppression is therefore essential in elderly patients.
      Research to determine the predictors for neutropenia has found that age itself is
      a significant risk factor. The benefit of treating elderly patients with colony
      stimulating factors is well established, with their use beginning in the first
      cycle of chemotherapy being crucial for minimizing neutropenia and its
      complications and facilitating the delivery of full-dose chemotherapy. Such
      prophylaxis should be routinely considered in elderly patients with cancer
      treated with myelosuppressive chemotherapy.

PMID- 14682117
TI  - Targeting the HER1/EGFR receptor to improve outcomes in non-small-cell lung
      cancer.
AB  - Non-small-cell lung cancer represents a growing global burden and remains a
      therapeutic challenge. Only small improvements in survival have been made with
      standard chemotherapeutic approaches to advanced disease in recent history. Novel
      biologic targeted therapies offer the potential of improving patient management
      and treatment outcomes in non-small-cell lung cancer. Prominent among these novel
      agents are the HER1/epithelial growth factor receptor (EGFR) inhibitors. One of
      these agents, gefitinib (Iressa), is already approved for use in advanced,
      refractory non-small-cell lung cancer. Erlotinib (Tarceva) is a promising
      HER1/EGFR inhibitor in phase III evaluation as first-line therapy combined with
      chemotherapy and as second-/third-line monotherapy in advanced non-small-cell
      lung cancer. In addition, erlotinib is being evaluated in combination with the
      angiogenesis inhibitor bevacizumab (Avastin), a strategy combining two new
      modalities in cancer treatment. Results of these trials will provide important
      information on optimal use of these new targeted therapies and may offer the
      promise of improving the treatment of non-small-cell lung cancer.

PMID- 14682118
TI  - Erlotinib: preclinical investigations.
AB  - Erlotinib (Tarceva) is an orally available selective small-molecule inhibitor of
      HER1/EGFR tyrosine kinase with a 50% inhibitory concentration of 2 nM for
      purified tyrosine kinase. This agent has been shown to produce stasis or
      regression of tumor growth in human cancer xenograft models, including non-small
      cell lung cancer models. Ongoing preclinical investigations indicate that
      inhibition of the MAPK and Atk signaling pathways downstream of HER1/EGFR may be
      required for optimal antitumor effects. Erlotinib exhibits inhibition of MAPK and
      Atk kinases at concentrations higher than those required for HER1/EGFR tyrosine
      kinase inhibition; such findings suggest that maximal inhibition of HER1/EGFR,
      requiring high erlotinib doses, is necessary for optimum antitumor activity.
      These considerations are supported by tumor models, including non-small-cell lung
      cancer models, showing dose-related antitumor effects up to high doses of
      erlotinib. Erlotinib exhibits additive antitumor effects when combined with
      chemotherapeutic agents (cisplatin, doxorubicin, paclitaxel, gemcitabine
      [Gemzar], and capecitabine [Xeloda]), radiation therapy, and other targeted
      agents (e.g., bevacizumab [Avastin]). Recent studies indicate that erlotinib
      inhibits the EGFRvIII mutant at concentrations higher than those required for
      inhibition of wild-type receptor. Ongoing investigation will help to determine
      optimal dosing and dose frequency of erlotinib in various cancers in the clinical
      setting.

PMID- 14682119
TI  - Clinical experience with the HER1/EGFR tyrosine kinase inhibitor erlotinib.
AB  - In phase I trials in healthy volunteers and patients with refractory cancers,
      erlotinib (Tarceva) was well tolerated and showed activity against non-small-cell
      lung cancer and other tumors. The dose identified for further clinical
      development was 150 mg/d; at this dose, erlotinib achieves high exposure, with
      maximum concentrations greater than 2,000 ng/mL and 24-hour area under the
      concentration-time cure greater than 35,000 ng.h/L. In a phase II trial in 57
      patients with previously treated advanced non-small-cell lung cancer, erlotinib
      treatment produced an objective response rate of 12.3% and a stable disease rate
      of 38.6%, with median duration of response of 19.6 weeks; median overall survival
      was 8.4 months and 1-year survival was 40%, with 9 patients remaining alive over
      follow-up of greater than 18 months. No grade 4 toxicity was observed, and grade
      3 toxicity was minimal. In an ongoing phase II trial in bronchioloalveolar
      carcinoma, erlotinib treatment has produced objective response in 26% of 50
      evaluable patients, with median duration of response not yet having been reached.
      An ongoing phase II trial is examining the combination of erlotinib with the
      angiogenesis inhibitor bevacizumab (Avastin) in previously treated non-small-cell
      lung cancer; phase I evaluation revealed no dose-limiting toxicities at tested
      doses and provided evidence of antitumor activity. Two phase III trials are
      examining erlotinib in combination with carboplatin (Paraplatin)/paclitaxel (the
      TRIBUTE trial) or cisplatin/gemcitabine (Gemzar) (the TALENT trial) as first-line
      treatment in advanced non-small-cell lung cancer. The phase III BR.21 trial is
      assessing erlotinib monotherapy in advanced refractory non-small-cell lung
      cancer. Results of these phase II trials will soon be available.

PMID- 14682120
TI  - Can rash associated with HER1/EGFR inhibition be used as a marker of treatment
      outcome?
AB  - Rash is a class effect of HER1/epidermal growth factor receptor (EGFR)-targeted
      agents, and has occurred with high frequency and in a dose-dependent manner in
      clinical trials of these agents in cancer patients. Analysis of phase II trials
      of erlotinib (Tarceva) in non-small-cell lung cancer, head and neck cancer, and
      ovarian cancer shows a significant association between rash severity and
      objective tumor response. Rash severity was highly significantly associated with
      survival in patients with non-small-cell lung cancer receiving erlotinib; median
      survival in patients with no rash was 46.5 days, compared with 257 days in those
      with grade 1 rash (P < .0001) and 597 days in those with grade 2/3 rash (P <
      .0001). Similarly, for the combined non-small-cell lung cancer, head and neck
      cancer, and ovarian cancer studies, median survival in patients with no rash was
      103 days, compared with 191 days in those with grade 1 rash (P = .0001) and 266
      days in those with grade 2/3/4 rash (P = .0001). Similar findings have been made
      with cetuximab (Erbitux) and in some settings with gefitinib (Iressa). The strong
      association of rash severity with response/survival suggests that rash may serve
      as a marker of response to erlotinib treatment and may be used to guide treatment
      to obtain optimal response. Dosing erlotinib at the maximum tolerated dose, which
      is associated with more frequent and more severe rash, may improve response rates
      and survival durations. Further study of the potentially important association
      between rash and outcome of treatment with EGFR-targeted agents is needed.

PMID- 14682121
TI  - Identifying predictive and surrogate markers of erlotinib antitumor activity
      other than rash.
AB  - The identification of predictive or surrogate markers of response to
      HER1/epidermal growth factor receptor (EGFR) inhibitor treatment would permit
      selection of patients most likely to respond to such treatment. Markers could
      consist of tumor characteristics (e.g., characteristics of the receptor or
      downstream signaling molecules and determinants of resistance) or host
      characteristics (e.g., pharmacokinetic parameters and toxicities). The occurrence
      of rash may constitute a surrogate marker of response to erlotinib (Tarceva)
      treatment in patients with non-small-cell lung cancer and other cancers. The
      erlotinib marker identification program has been designed to identify and
      investigate other candidate markers by analysis of a large number of clinical
      samples from patients enrolled in erlotinib trials in non-small-cell lung cancer,
      including the phase III TALENT and TRIBUTE trials of erlotinib combined with
      chemotherapy and the phase III BR.21 trial of erlotinib monotherapy in advanced
      non-small-cell lung cancer. This program should both contribute to understanding
      of the molecular biology of HER1/EGFR inhibition and result in identification of
      potential markers that can be evaluated in the clinical setting.

PMID- 14682122
TI  - [The Central Research Institute of Roentgeno-Radiology is 85 years old: past,
      present and perspectives of future development].

PMID- 14682123
TI  - [Interventional radiology in oncologic practice: review of research at the
      Central Research Institute of Roentgeno-Radiology].

PMID- 14682124
TI  - [Radiologic diagnosis in oncologic practice].

PMID- 14682125
TI  - [Current bioanalytic techniques in the laboratory diagnosis and in the monitoring
      of treatment outcome in oncologic diseases].

PMID- 14682126
TI  - [The role of positron emission tomography with C18-Fluorodeoxyglucose in clinical
      oncology].
AB  - The study was concerned with evaluation of the diagnostic potential of positron
      emission tomography (PET) with 18-FDG in clinical oncology and elucidation of its
      role in assessing therapy effectiveness. The Ecat Exact 47 and Ecat Exat HR+
      (Siemens) insatllations were used to examine 674 patients, with Whole Body
      protocol used in 585. PET with 18-FDG proved highly effective in diagnosing
      malignancies of the breast, lung, liver, pancreas, testis, brain and lymphoma as
      well as evaluating the efficacy of therapy.

PMID- 14682127
TI  - [Role of current MRI technology in the diagnosis of pancreatic tumors].
AB  - The Magnetom Vision unit (Siemens) with 1.5 T magnetic field and a Body surface
      coil was used to examine 87 patients with pancreatic tumors, adenocarcinoma--56,
      cystadenoma--3, and chronic pancreatitis--28. Magnetic resonance
      cholangiopancreatography (87), dynamic contrast-enhanced MRI (56) and MR
      angiography of the abdominal cavity (21) were used in conjunction with the
      paramagnetic drugs Magnevist (Shearing) or Omniscan (Nikomed). All necessary data
      for diagnosis and planning of surgical treatment of pancreatic tumors were
      obtained during a single examination due to complex use of present-day MRI
      techniques.

PMID- 14682128
TI  - [Arterial oil chemoembolization: a new method of treatment for pancreatic
      cancer].
AB  - A novel method of intra-arterial oily chemoembolization of pancreatic tumor has
      been developed. It slowed down regional blood flow in tumor dramatically due to
      injection of gemcitabin-in-oil. As a result, a prolonged contact of tumor with
      the highly-concentrated chemotherapeutic drug along the microcirculatory bed was
      assured. Enhanced antitumor effect, unaccompanied by any increase in systemic
      toxicity, was obtained by intensifying gemcitabin perfusion in the tissue. Tumor
      vessels had to be contrast-enhanced during the selective angiography of great
      vessels feeding the pancreas. Diagnostic angiography was performed in 63 patients
      with locally advanced tumors (T4NxMo) in 1999-2002. A total of 98 intra-arterial
      oily chemoembolizations (1-11 per patient) were carried out in 32 (51%). One or
      two-year survival rates in these patients after hemzar were 50 and 15%,
      respectively. Arterial oily chemoembolization is a safe and potentially effective
      method for the treatment of pancreatic cancer.

PMID- 14682129
TI  - [Colorectal cancer with synchronous metastatic involvement of the liver: results
      of single- and two-stage operations].
AB  - The data on the treatment of colorectal carcinoma and synchronous metastatic
      involvement of the liver in 41 patients are presented. After extensive
      resections, complications were reported in 45.5%, partial--12%. Post-operative
      mortality was 4.9%. Relapse-free survival in group 1 was 8.9 +/- 2.7 months,
      group 2-9.7 +/- 3.1 months. Hepatic tumor progression within 3.5-39 months (9.1
      +/- 2.4 months) was registered in 73.2%. Average survival in patients who had
      single-stage surgery was 23.1 months, after metachronous operations--23.7 months.
      Five-year survival rate was 12.1%.

PMID- 14682130
TI  - [Long-term regional chemotherapy for colorectal liver metastasis: significance of
      hepatic arterial anatomy in the surgical placement of the implantable infusion
      device].
AB  - The range and frequency of aberrant hepatic arterial anatomies and their
      significance for placement of implantable hepatic arterial infusion devices have
      been studied. The angiographs of 1439 patients treated at the Institute's Clinic
      (1985-2002) were used. The following 6 types of aberrant hepatic arterial anatomy
      were identified (J. Hiatt et al). Normal anatomy (type 1) was the most frequent
      (67.6%). The abnormal variants included: the aberrant left hepatic artery (LHA)
      running from the left gastric artery (LGA) (type 2)--9.9%; the aberrant right
      hepatic artery (RHA)--from the superior mesenteric artery (SMA) (type 3)--9.2%;
      the aberrant LHA from LGA with the aberrant RHA from SMA (type 4)--3.8%); the
      common hepatic artery running from SMA (type 5)--1.5%: other variants (type 6)-
      8.0%. Aberrant hepatic arterial anatomy occurred in every third patient. It was
      responsible for failed perfusion, frequent thrombosis of both hepatic arteries
      and infusion devices, suspension of regional chemotherapy and affecting its
      effectiveness. Proper identification of aberrant hepatic artery anatomy is vital
      for placement of implantable infusion systems.

PMID- 14682131
TI  - [Ultrasound diagnosis of angiopathy in antitumor therapy].
AB  - The ultrasound characteristics of arterial walls were assessed in 78 young and
      middle-aged male (42) and female (36) cancer patients (mean age 36 +/- 0.9)
      receiving radiation and/or polychemotherapy. The study was specifically concerned
      with quantitative and qualitative changes in the "intima-media" complex and the
      vasoactive dysfunction of the endothelium. We established the ultrasound
      characteristics of arterial walls, in particular, the damage done to the complex
      in the arteries in exposed sites, and angiopathies as a systemic manifestation of
      vasoactive dysfunction (polychemotherapy) or the combined effect on the vascular
      wall radiopolychemotherapy, vis-a-vis each therapeutic modality, separately and
      in combination.

PMID- 14682132
TI  - [Prognostication of hematotoxicity for radio- and chemotherapy in patients with
      breast cancer].
AB  - The effectiveness of radiation and chemotherapy for breast cancer depends on
      individual response to drug-induced toxicity. The response can be evaluated by
      means of myelodepression. To this end, changes in leukocyte DNA level after ex
      vivo gamma radiation test were used as a criterion. Patients, aged 29-78, with
      tumors stage IIIB-IV received standard radiotherapy (50 Gy) or cyclophosphamide
      methotrexate-5-fluorouracil (CMF). Clodronate alone was given to 26 patients and
      prior to a CMF course. The method proved prognostically effective since it
      revealed a significant inverse relationship between S-index and leukocyte nadir
      for both modalities. However, chemotherapy resulted in more pronounced
      leukopenia. With clodronate administration, the correlation was not significant.
      When clodronate was supplemented with CMF chemotherapy involved a significant
      relationship was observed between the two factors.

PMID- 14682133
TI  - [Geomagnetic field variation in early ontogenesis as a risk factor for
      oncopathology].
AB  - The data on 534 cancer patients with tumors of 15 different sites were evaluated
      to elucidate the influence of geomagnetic field (GMF) in certain months of the
      pre- and early postnatal periods on future incidence of cancer. We identified
      neoplasms of the breast, lung, urinary bladder, hypophysis, ovary, prostate,
      liver, Hodgkin's disease, lymphoma and, possibly, gastric cancer as GMF
      dependent. This relationship appeared to be idiosyncratic with every cancer
      variety. It was negligible in cases of esophagus, thyroid, uterine cervix and
      colorectal cancer. GMF variations as a carcinogenic factor in early ontogenesis
      can be assessed quantitatively.

PMID- 14682134
TI  - [Assessment of effectiveness of preoperative chemoradiotherapy in patients with
      T1B-2ABN0-1M0 cervical cancer].
AB  - The potential of preoperative radiochemotherapy in combined treatment of cervical
      carcinoma T1B-2ABN0-1M0 has been investigated. The use of cisplatin raised the
      feasibility of radical surgery from 69 to 87%, as compared with radiation alone,
      and increased 2-year overall and relapse-free survival to 92.6% and 89.4% vis-a
      vis 80.8% and 77.8%, respectively. No increase in complication rates in the
      blood, rectum or bladder during or shortly after treatment was reported.

PMID- 14682135
TI  - [Carcinogenic effects of single total-body irradiation with accelerated charged
      particles and gamma rays].
AB  - The study deals with the frequency of tumorigenesis in the endocrine glands,
      skin, soft tissues and internal organs of sexually mature female rats, exposed to
      accelerated charged particles with low LPE, such components of cosmic radiation
      as 645 MeV and 9 GeV protons and 4 GeV/nuclon ions of helium. The experiment
      continued until the animals' natural death. We established a high frequency of
      endocrine and uterine tumors and a comparatively wide range of localizations in
      rats which had received sufficient doses of gamma radiation. There were no
      intestinal or renal tumors, while very few tumors of the skin and soft tissues
      were detected in unexposed animals.

PMID- 14682137
TI  - [Treatment of hepatic hemangiomas: surgical method depending on type of disease].

PMID- 14682136
TI  - [Comparison of risk of mammary tumors developing in rats exposed to high-energy
      accelerated particles and gamma-ray radiation].
AB  - The frequency of tumorigenesis was investigated in the mammary glands of
      noninbred female rats and Wistar rats, after total-body exposure to a single dose
      of 60CO gamma radiation, 645 MeV and 9 GeV protons and 4 GeV/nuclon ions of
      helium. It was found that the relative biological effects of accelerated charged
      particles was significantly higher. This finding was obtained from calculations
      of the frequency of mammary tumors.

PMID- 14682138
TI  - [Preliminary results of selective combined therapy for patients with urinary
      bladder cancer].
AB  - The paper discusses the methods of complex treatment for invasive bladder cancer
      which includes radiation therapy, regional intraarterial chemotherapy with
      cisplatin drugs, selective hyperglycemia and local SHF-hyperthermia. Complete
      local response was reported in 18 (56%) out of 32 patients with stage II-IV
      tumors, partial--8 (25%), no response--6 (19%). The method appeared effective and
      safe; it offers good perspectives in bladder cancer treatment.

PMID- 14682140
TI  - [Results of radiotherapy in patients with stage-II Hodgkin's lymphoma with
      mediastinal lymph node involvement].
AB  - Depending on size of intrathoracic lymph nodes, 65 patients with Hodgkin's
      disease (stage II) were divided into two groups using the mediastinal-thoracic
      index (MTI): MTI = 0.22-0.3 prior to irradiation and MTI (0.3. Mediastinal nodes
      showed complete regression immediately after therapy (34-49 Gy aimed at
      mediastinum) in 12.3% only. In 44 patients (67.6%), complete response was not
      observed until 3-6 months after treatment, sometimes 24 months. Tumor recurred
      outside area of exposure 2-4 years in 4 (10.8%) in group I and 2 (7%) in group II
      (p(3.841). No correlation between recurrence rates and intrathoracic lymph node
      size was established. 10-year survival in both groups was 89.1 and 92.8%,
      respectively.

PMID- 14682139
TI  - [Results of combined therapy for brain tumors of various origin].
AB  - Treatment and prognosis of neurooncolical patients are largely determined whether
      tumor is a primary brain neoplasm or metastasis. Out of 284 brain cancer patients
      treated at the Institute's Clinic, 262 had primary tumors and 22--metastases from
      various sites. Combined therapy was given to 273: surgery--241, radiotherapy--273
      and polychemotherapy--263. Three-year survival was reported in patients with
      anaplastic astrocytoma stage II (90%), stage III--(51%) and stage IV--(14%).
      Eighty percent of cases of brain metastases have been followed up for 9 months.

PMID- 14682141
TI  - [Accelerated fractionation regimens in radiotherapy of inoperable non-small-cell
      lung cancer].
AB  - The results of definitive radiation treatment (1988-2000) for 375 patients with
      inoperable non-small cell lung cancer were analyzed. Three regimens of
      fractionation were used: (1) accelerated fractionation (AF)--(133), 2.5 Gy, 3
      days a week, to a total of 47.5--55 Gy; (2) accelerated hyperfractionation (AHF)-
      (93), 1.25 Gy, daily, to a total of 60-72.5 Gy and standard fractionation (SF)-
      (149), 2 Gy, daily, to a total of 58-68 Gy. The advantages of AHF were
      established as regards complete regression rate (54.9% vs. 18.6%--SF and 18.1%-
      AF; p(0.001), median survival (30.5(2.4 months vs. 18.9 (1%--SF (p = 0.004) and
      20.4 (2.4--AF (p = 0.004)), and 3-year survival (36.6% vs. 16.7%--SF (p = 0.005)
      and 15.5%--AF (p = 0.005). 17.9%, 9.0% (p = 0.11) and 8.1% (p = 0.08) have
      survived, respectively. Overall survival in the AHF group was superior in stages
      IIB--III; in stage I, the results were identical. Immediate response to radical
      radiotherapy appeared the only statistically significant factor of survival (p =
      0.005-0.008) in all the groups.

PMID- 14682142
TI  - [Choice of fractionation regimen in radiotherapy of inoperable esophageal
      cancer].
AB  - The results of definitive radiation treatment for 303 patients with inoperable
      esophageal cancer were analyzed. Four regimens of fractionation were used: (1)
      accelerated hyperfractionation (AHF) (70)--1.3 Gy, twice a day, 5 weeks, to a
      total of 57.2-70 Gy; (2) AHF (49)--1.5-d = 1.5 Gy to a total of 54-63 Gy; (3) AHF
      (37)--1.7-d = 1.7 Gy to a total of 56.1-57.83 Gy and (4) standard fractionation
      (SF) (147) to a total of 58-70 Gy. The complete regression rate in the AHF groups
      (1.3-1.7, 69, 61 and 73%, respectively) was significantly higher than in that of
      SF (38%) (p(0.01); the median survival in the AHF groups and SF--21, 22, 12.3 and
      14.3 months, respectively, and the 5-year survival 14, 12, 4 and 0%,
      respectively; all the differences in the groups 1.3 and SF were significant. The
      common independent prognostic factors for all patients were age (p = 0.04),
      immediate effect of radiation therapy (p = 0.01) and the length of tumor (p =
      0.02).

PMID- 14682143
TI  - [Cervical, uterine and ovarian carcinoma: results and perspectives of research
      conducted at the RF Health Department's CRIRR (Central Research Institute of
      Roentgeno-Radiology)].
AB  - The results of the main investigations of diagnosis, radiation therapy and
      combined treatment of patients with cervical (5,000), uterine (1,900) and ovarian
      (1,000) carcinoma are presented.

PMID- 14682144
TI  - [Basic principles and implementation of intensive radiotherapy and
      chemoradiotherapy for cancer patients].

PMID- 14682146
TI  - [Use of the topometric system in preparation of patients for radiotherapy TCR
      100].

PMID- 14682145
TI  - [Characteristics of the national standard for quality assurance of radiotherapy
      in oncologic patients].

PMID- 14682147
TI  - [Current radiotherapy for primary and metastatic cancer of the vagina].

PMID- 14682148
TI  - [Fusion--a marriage of convenience].

PMID- 14682149
TI  - [Repolarization of ventricular myocardium--discoveries and questions].

PMID- 14682150
TI  - [The QT interval and its dispersion: what is its role in clinical practice?].

PMID- 14682151
TI  - [Identification of the genetic basis of an unusually rare disease--the long QT
      interval syndrome--brought an understanding of important arrhythmogenic
      mechanisms].

PMID- 14682152
TI  - [Comparison of various methods of correction of QT intervals during exercise in
      familial long QT interval syndrome].
AB  - BACKGROUND: Pathologic prolongation of QT interval is related to increased risk
      of arrhythmias. Changes of this parameter are influenced by many conditions, the
      most important is heart rate. Several formulas have been proposed for
      mathematical description of QT interval/heart rate relationship. The aim of this
      study was comparison of different QT interval correction formulas in families
      with congenital long QT syndrome (LQTS). METHODS: In 28 members of 6 families
      with LQTS occurrence bicycle ergometry testings were performed. QT and RR
      intervals were measured before exercise, at peak exercise and in the 1st and the
      6th minute of restitution. For QT interval correction single-parameter formulas
      by Bazett, Fridericia, Malik and Framingham study were used. In 3 families the
      results could be correlated with genetically proved diagnosis (KCNQ1 gene
      mutations in 2 families, HERG-KCNH2 gene mutation in the other). RESULTS: In the
      described group the genetically established diagnosis of LQTS correlated at best
      with values obtained with correction by Bazett. All the mutation carriers were
      correctly identified only by this method. The Fridericia, Malik and Framingham
      formulas failed to identify 2 patients--mutation carriers (both KCNQ1 and HERG
      KCNH2 mutations). DISCUSSION: Because of simplicity the Bazett formula remains
      the most common method of QT interval correction. Moreover, in our study this
      formula appeared to be the most sensitive for clinical diagnosis of LQTS.

PMID- 14682153
TI  - [QT interval dispersion in hypertensive diabetics and in patients with
      hypertension with chronic heart failure without diabetes].
AB  - AIM: Our aim was to: 1. compare QT dispersion from routine ECG in diabetic and no
      diabetic patients with congestive heart failure, 2. describe associations between
      QT dispersion and circadian blood (BP) pressure variation in type 2 diabetic
      patients with congestive heart failure (CHF). PATIENTS AND METHODS: 122 patients
      admitted to hospital due to CHF in the period between years 2000-2001 have been
      divided into 2 groups: group 1:70 patients (m: 40, f: 30, mean age 64.7 +/- 9
      years) with type II diabetes mellitus (DM), group 2:52 patients (m: 28, f:24,
      mean age 62.5 +/- 10.9 years) without DM. Diagnosis of CHF was made clinically
      and proved by ECG and ECHO (EF < 40%), DM was defined clinically or by using oral
      glucose tolerance test (75 g glucose, 2 h blood glucose > 11.1 mmol/l). The QT
      interval was measured from the beginning of the QRS complex to the end of the T
      wave from routine 12-lead ECG. QT intervals were corrected for heart rate using
      Bazett's formula. QT dispersion (QTd) and rate corrected QT dispersion (QTc) were
      defined as the difference between the maximum and minimum QT and QTc intervals,
      respectively. Ambulatory blood pressure (AMBP) was measured by an oscillometic
      technique. Diabetic patients with CHF were divided both according to below and
      above the median QTc dispersion (65 ms). STATISTICAL ANALYSIS: Chi-square and
      Student's t-test. Significant differences were assumed of p < 0.05. RESULTS: Both
      groups were matched by gender, age, duration and intensity of hypertension, the
      presence and intensity of obesity, hyperlipidemia (TC, TG, LDL-C, HDL-C) and
      smoking habits. Diabetic patients with CHF had significantly longer QTc interval
      (maximum and minimum), QT dispersion and QTc dispersion compared with non
      diabetic patients with CHF. Diabetic patients with CHF with QTc dispersion > 65
      ms had significantly higher night systolic (133 +/- 14 vs. 112 +/- 14) and
      diastolic (80 +/- 11 vs. 65 +/- 6) BP and significantly higher night/day ratio
      for both systolic (0.94 +/- 0.05 vs. 0.86 +/- 0.06) and diastolic (0.89 +/- 0.07
      vs. 0.80 +/- 0.05) compared with diabetic patients with CHF with QTc dispersion <
      65 ms. CONCLUSION: Diabetic patients with CHF are higher risk than non-diabetic.
      Our data describe both factors related to cardiovascular risk in diabetic
      patients with CHF-prolongation of the QT and QTc dispersion and reduced nocturnal
      blood pressure.

PMID- 14682154
TI  - [Antibiotic prophylaxis in patients with acute hemorrhage due to portal
      hypertension--personal experience].
AB  - Acute bleeding from upper part of gastrointestinal tract is a frequent and
      serious complication affecting 20 to 60% of patients with liver cirrhosis and
      portal hypertension. It is associated with a high death rate of 30 to 50% and a
      frequent relapse of bleeding occurs in up to 40% of these patients. The most
      recent meta-analyses have shown that bacterial infection is an independent factor
      in the failure of blood hemostasis and significantly influenced mortality in
      these patients. The authors investigated 25 patients with acute bleeding from the
      upper part of gastrointestinal tract due to portal hypertension in patients with
      liver cirrhosis. Irrespective of the proved bacterial infection the patients were
      given antibiotic prophylaxis. In 13 patients the authors administered norfloxacin
      orally and 12 patients were treated intravenously with ampicilin/sulbactam. The
      prophylaxis of the bleeding cirrhotic patients by norfloxacin (orally) resulted
      in a statistically significant prevention of early relapse as compared with the
      therapy by ampicilin/sulbactam (intravenously). The death rate reached 40% in
      spite of the antibiotic prophylaxis. There was no significant difference in the
      death rate between the two groups with different treatments.

PMID- 14682155
TI  - [The long QT interval syndrome].
AB  - The syndrome of long QT interval frequently follows to syncope or a sudden
      cardiac death on the basis of originated polymorphic ventricular tachycardia of
      the "torsade de pointes" type. The prolongation of the QT interval in the
      hereditary form is based on mutation of the genes responsible for the formation
      of sodium and potassium channels. The authors analyze the occurrence, clinical
      findings, therapy and genetic and electropathophysiological connections of the
      most frequently occurring genotype LQT1, LQT2 and LQT3 as well as the acquired
      forms of the syndrome of long QT interval.

PMID- 14682156
TI  - [Dr. Frantisek Hendrich, 27 October 1913--25 November 1985].

PMID- 14682157
TI  - [Did West Nile Fever (WNF) appear in Poland? Position of the Expect Committee
      appointed by the Chief Sanitary Inspector].
AB  - Position of the Expect Committee appointed by the Chief Sanitary Inspector
      regarding the possibility of occurrence of West Nile Fever in Poland.

PMID- 14682159
TI  - [Parainfluenza type 3 virus infection in neonates with cardiac arrhythmia].
AB  - The aim of the study was to assess the frequency of the occurrence of
      parainfluenza type 3 virus infection in neonates with cardiac arrhythmia. In 12
      (17%) out of 70 of neonates parainfluenza type 3 virus infection was recognized
      basing on serologic hemagglutinin inhibition test. Ten of them were diagnosed
      with mild course of myocarditis. Among 12 neonates infected with parainfluenza
      type 3 virus supraventricular and ventricular arrhythmia was observed in 5 and
      mild periodical bradycardia was diagnosed. None of the neonates were treated with
      antiarrhythmic medications. The authors would like to point out that
      interpretation of the serologic tests in neonates are difficult.

PMID- 14682158
TI  - [Prevalence of respiratory viruses in elderly people].
AB  - We analysed the presence of respiratory tract viruses in 206 elderly people (more
      than 65 years old). To identify viruses we used immunofluorescence method. The
      study revealed respiratory virus infection in about one third of examined
      patients. We found the most frequent infection with parainfluenza viruses. We
      found also more frequent prevalence of respiratory viruses in the oldest subgroup
      (more than 75 years old). No correlation between presence of respiratory viruses
      and smoking, diabetes or congestive heart failure was found.

PMID- 14682160
TI  - [Susceptibility to respiratory infections in school children after measles.
      Results of epidemiological study in Krakow].
AB  - Purpose of the study was answering the question whether measles experienced in
      young children may lead to an increased susceptibility to respiratory infections.
      In order to verify the hypothesis, the analysis of the prospective study on
      respiratory morbidity in children has been carried out in Krakow. In the course
      of the study a detailed epidemiologic interview on current and past respiratory
      diseases diagnosed by physician was collected in consecutive years of the survey
      (1995-1997). Susceptibility to respiratory infections has been defined as excess
      number of respiratory episodes over the third quartile of the distribution of
      number of episodes in upper and lower respiratory tract. The results of the study
      showed that susceptibility to upper respiratory infections was about twice so
      high (OR = 1.97; 95%CI: 1.27-3.05) among those children who experienced measles.
      Amongst other factors potentially responsible for an increased susceptibility to
      respiratory infections, only atopy and fungal exposure within home were
      associated with the higher risk The analysis performed for lower respiratory
      episodes confirmed the findings obtained for upper respiratory tract infections,
      however, the effect of atopy was much higher pronounced.

PMID- 14682161
TI  - Human cytomegalovirus serological status in patients with interstitial lung
      diseases.
AB  - Recent data, especially from immunocompromised patients, suggest that human
      cytomegalovirus (HCMV) plays an important role in lung pathology. In this study
      the serological status of HCMV infection and characteristic of the HCMV infected
      patients with interstitial lung diseases were determined. The subjects were
      enrolled prior to immunosuppression therapy introduction.

PMID- 14682162
TI  - [Assessment of etiological diagnostics in adults with aseptic encephalomeningitis
      -own material].
AB  - OBJECTIVE: Epidemiologic, etiologic and clinical assessment of patients with
      aseptic encephalomeningitis (AE); evaluation of efficacy of diagnostic process.
      METHODS: From January 1996 to August 2002, in seventy seven patients AE was
      diagnosed on the basis of lymphocytic predominance in cerebrospinal fluid (CSF)
      and negative culture of CSF. Analysis comprised: etiology, course of the disease
      and spectrum of used diagnostic tests. RESULTS: In 48/77 patients (62.3%)
      etiology was not identified. In 8/77 patients (10.3%) herpes simplex encephalitis
      was diagnosed, in 7/77 (9.1%) neuroborreliosis, in 6/77 (7.8%) tuberculosis
      encephalitis, in 3/77 (3.9%) listerial meningitis, in 3/77 (3.9%) mumps
      meningitis, and in remaining 2/77 (2.6%) tick-borne encephalitis. The incidence
      of AE was higher in summer (42.9%) than in any other season. In 14/77 patients
      (18.2%) the episode of unconsciousness occurred in the course of the disease. In
      6 of these 14 patient etiology was unknown, in 4 tuberculosis AE, in 2 herpes
      simplex encephalitis and in 2 neuroborreliosis was diagnosed. In 7 of 77 patients
      (9.0%) et least one episode of convulsions occurred. CONCLUSIONS: In 62.3% of
      patients etiology remained unknown due to clinical and economic reasons. Aseptic
      encephalomeningitis in adults not always mean the viral etiology and mild course
      of the disease.

PMID- 14682163
TI  - [Epidemiological, clinical, immunological and virological characteristics of HIV
      1 infected patients at the moment of initiation of antiretroviral therapy].
AB  - OBJECTIVE: The aim of the study was epidemiological, immunological and
      virological analysis of the cohort of the HIV-1 infected patients (pts) who had
      started highly active antiretroviral therapy (HAART). METHODS: Retrospective
      analysis of pts. data. RESULTS: 138 pts., mainly men, had started HAART since
      January 1996 till December 2000. Risk groups for HIV infection were as follows:
      IVDU: 63.8%, heterosexual: 23.9%, homosexual: 11.6%. 34% of pts. fulfilled
      criteria of initiating HAART already at the time of HIV-1 infection diagnosis. In
      30.4% pts. 63 AIDS defining illnesses were diagnosed before HAART. We observed a
      very advanced HIV infection in our pts. at the time of HAART initiation (61.2%
      pts, with CD4 T cells count < 200/mm3; 58% pts. with HIV RNA level > 100,000
      copies/mL). During HAART in 15.2% pts. 24 AIDS defining illnesses were recognized
      (in 7 cases it was reactivation of previous opportunistic infection, diagnosed
      before treatment). CONCLUSIONS: Our observations indicate that HIV infection in
      analysed group of pts. was diagnosed very late, in advanced stages of the
      disease. Most of our pts. were young IVDUs. Factors mentioned above had negative
      influence on the efficacy and tolerability of HAART.

PMID- 14682164
TI  - [HBV and HCV coinfections in children--own investigations].
AB  - Problem of HBV and HCV coinfection is controversial. HCV superinfection seems to
      be the co-factor of HBV infection, so as factor inhibiting HBV replication.
      According to some authors in HBV, HCV co-infection more advanced morphological
      liver changes and progression to hepatocellular carcinoma were observed. It
      concerns so patients with active as an "occult" hepatitis B. In this work the
      results of our own investigations were presented in which beneficial influence of
      HCV superinfection on chronic B hepatitis in children was revealed. Our study
      confirmed opinions of both viruses interference.

PMID- 14682165
TI  - [Risks associated with hepatitis infection in patients with hepatitis C and
      opportunities for prophylaxis].
AB  - Patients with chronic hepatitis C remain at risk of acquiring hepatitis A
      infection and additional liver injury. The estimated risk of HAV infection in HCV
      patients is similar to that in general population but may be higher in anti-HCV
      positive drug users. Despite some controversies available data indicate that
      hepatitis A infection is associated with much higher incidence of hepatitis
      fulminans and mortality rate in individuals with pre-existing liver disease. In
      Poland about 60% of all HCV-infected adults have natural immunity to HAV, however
      majority of those under 35 years majority remains unprotected. Currently
      available inactivated HAV vaccine proved to be highly immunogenic and safe in
      patients with hepatitis C. The vaccination should be administered in each
      unprotected patient upon diagnosis of HCV infection.

PMID- 14682167
TI  - [Some clinical aspects of hepatitis A during the epidemiologic increase of
      morbidity in Gdansk Providence in the years 1991-1993].
AB  - OBJECTIVE: Clinical analysis of hepatitis A cases among patients hospitalized
      during the last increase of morbidity, in years 1991-1993, in Gdansk province.
      MATERIAL AND METHODS: Retrospective examination of 3040 cases of hepatitis A from
      the departments of infectious diseases in Gdansk that was executed basing on
      medical documents. RESULTS: There were no significant differences in number of
      patients according to sex (51.8%--men), persons in age 11-20 yrs were in the
      majority (39.8%), 91% of patients were younger than 30 yrs. The time of treatment
      was not equal, it usually fluctuated from 2 to 4 weeks (92% of cases). Groups of
      men became more numerous in comparison to women parallel with prolongation of
      hospitalization time. Patients older than 20 yrs were more often observed and
      cured at the hospital than younger ones. Mild clinical course was observed in
      1464, moderate in 1548, severe in 26 and fulminant in 2 cases. In some cases
      there were noted symptoms of malfunction of other organs as skin, joints,
      respiratory, cardiovascular, digestive systems. 417 patients demonstrated
      serological markers of persistent or past HBV infection. CONCLUSIONS: 1. The
      course of initial disease was similar as in other papers. 2. More than 90% of
      patients were treated no longer than 6 weeks. Together with prolongation of
      hospitalization time groups of men and older patients became more numerous. 3.
      Mild and moderate cases dominated in clinical analysis, two deaths were noted. 4.
      Malfunction of other organs was observed in nearly of 30% of patients.

PMID- 14682166
TI  - [Epidemiological characteristics of hepatitis A in Gdansk Providence in years
      1991-1993].
AB  - AIM: Epidemiological analysis of hepatitis A morbidity increase observed in years
      1991-1993, in Gdansk province. MATERIAL AND METHODS: Retrospective analysis
      concerned medical documentation of 3040 hepatitis A cases from Gdansk Province.
      RESULTS: No significant sex distribution differences among the hepatitis A cases
      were observed, incidence among men and villagers was essentially higher. The
      hepatitis A incidence increase observed in Gdansk Province was multifocal and
      seasonal. In 1926 (63.4%) cases the probable route of infection was ascertained.
      The most often potential source of infection was an ill member of the close
      family. Analysis of employment pointed at the majority of the morbidity among
      people with a low level of education. The most numerous group consisted of
      patients in age 11-20 yrs. There were no significant differences in comparison of
      age groups according to the place of living (towns vs villages).

PMID- 14682168
TI  - [Cases of ineffective anti-hepatitis B vaccination--own observations].
AB  - Between 1999-2001 there were 6 patients with acute hepatitis B, previously
      vaccinated according to the recommended schedule of anti-hepatitis B immunization
      for adults, hospitalized in the Department of Infectious Diseases (Bytom,
      Silesian University Medical School). The study presents epidemiological and
      clinical analysis of these cases. Special attention is paid to possibility of
      immune response failure in spite of anti-hepatitis B vaccination. It is
      emphasized, that efficiency of active hepatitis B prophylaxis should be verified
      by estimation of serum anti-HBs antibodies, especially in patients with planned
      surgery.

PMID- 14682169
TI  - [Susceptibility to antimicrobial agents of enteroaggregative Escherichia coli
      strains isolated from children with diarrhea].
AB  - Enteroaggregative Escherichia coli (EAEC) are responsible for infant's persistent
      secretory diarrhea, traveler's diarrhea and outbreaks. Since isolated all over
      the world EAEC strains show a low to high level of resistance to antimicrobial
      agents, the aim of the study was to determine antimicrobial susceptibility and
      beta-lactamases extended spectrum (ESBL) production in vitro among 55
      enteroaggregative E. coli strains isolated from children with diarrhea. Among the
      17 antimicrobial agents tested, most of them showed good in vitro activity
      against EAEC isolates examined, apart from ampicylin and piperacylin (about 30%
      resistant EAEC strains). Three of 55 examined EAEC isolates were ESBL--producing
      strains. Because of the presence of ESBL--producing as well as resistant to
      antimicrobial agents EAEC isolates among enteroaggregative E. coli strains
      examined, treatment with antibiotics should be undertaken according to
      antibiogram.

PMID- 14682171
TI  - [Health promotion and health care system reform in Poland].
AB  - The development of health promotion is determined by the defined changes of
      health situation of population, which occur in time. Contemporary methods of
      health promotion were initiated in 1970's, when the problem of increase of
      civilization (behavioural) diseases strongly related to lifestyles, was noticed.
      Health promotion programmes in Poland in spite of many achievements in the
      conceptualization phase, encounter difficulties in implementation, because of
      lack of appropriate structural solutions and financial support for this important
      public health area.

PMID- 14682170
TI  - [Lalonde's paradigm, World Health Organization and new public health].
AB  - The authors present the origins and evolution of the New Public Health idea
      assuming the fundamental significance of Lalonde's health field concept in this
      process. The other crucial events which contributed to it was the formulation and
      implementation of WHO strategy HFA 2000, publication of Ottawa Charter, defining
      by WHO the essential public health functions and concepts of Gro Harlem Bruntland
      from 1998-1999 when she was the Director General of WHO. Authors present for
      discussion their working definition of New Public Health, which is based of the
      public health definition of J. Nosko et al. from 2001.

PMID- 14682173
TI  - [Physicians's attitude toward patient education].
AB  - In the article patient education is recognized as a process of changing
      knowledge, attitudes and skills and influencing behaviour to improve health. In
      2001 a questionnaire survey was carried out among 415 physicians to assess range
      of patient education, physicians' attitudes, social influences supporting and
      hindering this activity and barriers for performance. It was concluded that
      patient education was quite wide range activity among young physicians and
      attitudes were more or less positive. Despite of that social influences were not
      strongly supportive for patient education and there was a lot of barriers,
      especially lack of time, too many patients and administrative tasks.

PMID- 14682172
TI  - [Breast cancer prevention--awareness and health behavior changes in women in 1998
      2002].
AB  - AIM: To find changes in the proportion of women who declared they were aware of
      breast self examination (BSE) and performed it regularly in 1998 and in 2002, as
      well as in the proportion of those who declared health behaviour connected with
      secondary prevention of breast cancer. Also to define the groups of women who
      especially need health education and prophylactic intervention. METHODS: The
      results of two breast cancer prevention surveys on representative samples of
      Polish women aged over 18 + years were compared. The data were analysed in groups
      of women categorised according to selected demographic and social factors.
      RESULTS: The substantial increase in the proportion of women who declared that
      they performed mammography in 2002 in relation to 1998. The percent of women who
      declared other prophylactic behaviours in 2002 did not change or was even lower
      in some groups. The decrease of doctors' activity in the field of secondary
      prevention of cancer was also observed. CONCLUSIONS: 1. It is important to
      continue educational work and intervention measures concerning breast cancer
      prevention, with special attention to the most neglected groups of women. 2. It
      would be important to continue educating doctors in prophylactic breast
      examination and establish some obligatory rules in this area. 3. It would be
      beneficial to introduce breast cancer screening in Poland on the national scale.
      A model of such screening has already been implemented.

PMID- 14682174
TI  - [Assessment of usefulness of visual analogue scale (VAS) for measuring adolescent
      attitude toward unhealthy behaviors].
AB  - In the last two decades the visual analogue scale has been more frequently used
      for measuring the psychosocial determinants of health, its disorders and
      unhealthy behaviours. In 1999 in Health Promotion Department of the National
      Institute of Hygiene multidimensional investigations on self-assessment of health
      and life style of adolescents were undertaken and evaluation of visual analogue
      scale usefulness for health promotion research was one of the aims of these
      investigations. The data were obtained from randomly selected sample of 682
      schoolchildren aged 14-15 years attending to public and private schools of
      Warsaw. The questionnaire contained the questions about frequency of alcohol
      drinking, cigarette smoking, drug using and manifestation of aggression.
      Simultaneously, respondents were asked, how much these behaviours are usefully
      for coping with everyday events. The answers of usefulness of unhealthy
      behaviours were measured on tenth centimetre line from "not at all" to
      "completely". The study shows that adolescents who presented unhealthy behaviours
      more often are more likely to give higher value to these behaviours in coping
      with their problems. Moreover, adolescents' attitude toward unhealthy behaviours
      varies according to gender, kind of alcohol, frequency of being drunk, proposals
      to buy the drugs, carrying the weapon and frequency of injures from violence. The
      analyses confirm the usefulness of visual analogue scale for study on
      psychosocial and life style determinants of health.

PMID- 14682175
TI  - [Use of medical record linkage in epidemiologic studies].
AB  - The article presents two methods of records linkage, deterministic and
      probabilistic, applied in epidemiological studies and medical registers. Sources
      of selection bias linkage was considered. The modified deterministic linkage by
      random selection of one from non-unique records was elaborated. The quality of
      applied method of record linkage in survival analysis was empirically evaluated.
      Usefulness of record linkage in epidemiology was talked over.

PMID- 14682176
TI  - Global situation of the HIV/AIDS pandemic, end 2003.

PMID- 14682177
TI  - Influenza.

PMID- 14682178
TI  - [Intestinal transplant in patients with parenteral nutrition at home].
AB  - Failure of the intestine, whether due to functional or anatomical reasons,
      constrains Parenteral Nutrition Therapy in children or adults who, as a result of
      intestinal resections, alterations in motility, diseases of the microvilli or
      other reasons, present insufficient intestine to cover their needs in terms of
      nutrients and fluids. Nonetheless, the maintenance of support with parenteral
      nutrition at home in subjects with irreversible intestinal failure is not without
      life-threatening complications: liver disease, recurrent sepsis and loss of
      central routes recommend the assessment of the indication of intestinal
      transplant in this group of patients. The incidence of morbidity and mortality
      after intestinal transplant is greater than in other transplants (kidney, liver),
      but the long-term survival is around 50-60%. In Spain, 7 transplants (6 children
      and 1 adult) have been performed so far: 3 of intestine alone, 3 of liver plus
      intestine and 1 mutivisceral transplant. In 4 cases, the indication for
      transplant was due to terminal liver disease, with the remainder being due to the
      loss of venous access, intractable diarrhoea and intra-abdominal desmoid tumour,
      respectively. Except for one girl who presented severe rejection of the graft,
      the rest achieved digestive autonomy. One boy has presented lymphocyte neoplasia
      (PTLD) after 2 years and another died after the transplant as a result of a
      routine liver biopsy (with functioning grafts). Of the 38 patients assessed for
      transplant, 18 were considered as candidates and of these, three youthful
      candidates for hepato-intestinal transplant (with short intestine syndrome) have
      died while on the waiting list and a fourth in the operating theatre prior to an
      attempted multivisceral transplant. Intestinal transplants must not be considered
      as the last desperate therapeutic option in patients with permanent intestinal
      failure. The type of graft, clinical expertise and the use of new inducers
      (Sirulimos) all contribute to the results of this therapy, in which survivors
      remain free from parenteral support and can take up once more their day-to-day
      activities, can improve over time.

PMID- 14682180
TI  - [Are Doctors familiar with enteral nutrition at home? Opinion poll in the
      province of Tarragona].
AB  - At our hospital, there is an At-Home Enteral Nutrition programme (NED in its
      Spanish acronym) with participation of the Clinical Nutrition Unit and the
      Pharmacy Service. The products and all necessary material are dispensed directly
      to the patient's home and nutritional follow-up is carried out. As a lack of
      information on various aspects of NED was detected among prescribing doctors, we
      decided to carry out a survey to assess the level of awareness and the opinion of
      doctors in the province of Tarragona with regard to NED. They were asked if they
      knew the indications and characteristics of the different enteral nutrition
      preparations, as well as their opinion on who should do the follow-up of the
      patients and on how dispensation should be organized. With the results obtained,
      we conclude that doctors rarely prescribe NED and are not familiar with the
      indications nor with enteral nutrition preparations (77.5% and 89%,
      respectively), although they are interested in the subject. They feel that
      dispensation should be done directly at the patient's home (43%) and that follow
      up should be through a specialized team (57.6%).

PMID- 14682179
TI  - [Effect of low glycemic index diets in hyperlipidemia].
AB  - INTRODUCTION: After consuming a low-glycemic-index (GI) diet, patients with
      diabetes and hyperlipidemia showed reduced biochemical markers of dyslipidemia.
      Despite Mexican food habits include low-GI foods; there have not been published
      results on the effect of low-GI diet on hyperlipidemia. The aim of this study was
      to compare the effects of a low and high glycemic index (GI), using cultural
      based foods to Mexicans on LDL, HDL, total cholesterol, and triacylglycerol.
      METHODS: Eight volunter's individuals with hyperlipidemia participated in the
      study. Six diets were designed, three with low-GI and three with High-GI. The
      study design included 2 times 3-week treatment periods with a 4-week washout
      period between treatments. Biochemical data was obtained at the start and finish
      of each dietary period. Subjects completed 1-day dietary diaries during the first
      and third weeks of each of the treatment periods. Paired t-test was used to
      compare biochemical data at the baseline and after the dietary treatment periods.
      RESULTS: At the end of the study periods, total cholesterol (P < 0.05) and LDL (<
      0.02) were improved significantly by 10 and 13% respectively. A low GI diet
      containing Mexican foods during three week period may help to improve LDL and
      total cholesterol in individuals with hyperlipidemia.

PMID- 14682181
TI  - [Height, leg length, adiposity and metabolic-cardiovascular risk in women aged 35
      55 years].
AB  - OBJECTIVE: To determine the relative importance of the components of height in
      the evaluation of the adiposity and the cardiovascular and metabolic risk profile
      in women aged 35-55 years. METHODS: Cross-sectional study. 30 healthy women were
      recruited. Components of height (total height, trunk length, leg length) was
      compared with body mass index (BMI), body fat, and different measures of central
      adiposity: waist circumference, waist-to-hip ratio, and sagittal abdominal
      diameter. Metabolic-cardiovascular risk was assessed by serum levels of glucose,
      triglycerides, total cholesterol, HDL-cholesterol; and systolic (SBP) and
      diastolic (DBP) blood pressures. Biological factors and socio-economic status
      influences was evaluated. RESULTS: Glucose levels were inversely associated with
      height (r = -0.395; p < 0.05). When analyzing this association for components of
      height, glucose was negatively related to leg length (r = -0.447; p < 0.05) and
      showed no association with trunk length or the superior segment. The height or
      its components were not significantly related to BMI, percentage of body fat,
      estimators of body fat distribution, blood pressure or the rest of metabolic
      parameters. Education level was associated with leg length (r = 0.390; p = 0.037)
      and negatively related to glucose levels (r = -0.517; p = 0.004) and other risk
      factors. CONCLUSIONS: These data support the hypothesis that adiposity is
      conditioned by weight and that stature is inversely related to risk of metabolic
      and cardiovascular disorders in women aged 35-55 years, and suggest that legs
      length is the component of stature that conditions this result and that socio
      economic status influences in this association. Factors which might explain this
      association remain to be determined.

PMID- 14682182
TI  - [Age-related changes in the dietary intake of elderly individuals. The Euronut
      SENECA study].
AB  - There are few longitudinal studies linking eating habits, diets, nutritional
      content and their repercussions on health. For this reason, the European Union's
      Concerted Action on Nutrition and Health, Euronut, organized an international,
      multi-centric longitudinal cohort study in 1988 in an attempt to analyze these
      factors in various food cultures of Europe. This study was given the name SENECA
      (Survey in Europe on Nutrition and the Elderly: a Concerted Action). To this end,
      several types of tests were performed: a general questionnaire (collecting
      information on: personal details, social and demographic status, socio-economic
      situation, lifestyle and physical activity and dietary or other living habits), a
      dietary study, anthropometric and biochemical parameters. The present paper has
      attempted to assess the differences due to gender and age (in the same subjects),
      for which purpose data has been collated from a group of individuals between 71
      and 80 years of age on the quantitative and qualitative food consumption, energy
      and nutrient intake and their contribution to the recommended daily intake. The
      four groups of foods most consumed in both parts of the study were: fruit, milk
      and its derivatives, vegetables, and cereals and their derivatives, during the
      four years that have elapsed, a significant reduction was seen in the consumption
      of certain foods, both in the total of the sample and for the distribution by
      gender. As a result, with a four-year increase in age, i.e. in the second part of
      the study, a reduction in energy intake was observed to have a considerable
      impact on the intake of most micronutrients. The percentile distribution shows
      that there are individuals who consume very small amounts (or nothing at all) of
      certain foods. High percentages of individuals were seen not to cover the
      recommended intake.

PMID- 14682183
TI  - [Subjective global assessment in neoplastic patients].
AB  - As malnutrition is a common complication among patients with cancer, it seems
      necessary identifying it with simple tools. Subjective Global Assessment (SGA) is
      useful to evaluate nutritional status on a basis of clinical parameters and can
      be used by any clinician with a basic training. Our intention is to determine
      usefulness of SGA applied by staff not working at Clinical Nutrition to guess if
      they identify properly malnourished patients. We included in our study thirty
      male and female patients with several types of active neoplasm who were being
      treated with chemo or radiotherapy. Oncology and Clinical Nutrition staff used
      SGA separately after the patients answered the form; there were also taken
      biochemical and anthropometrical determinations. Sixty-three percent of patient
      were diagnosed as malnourished or suspected being so by Oncologists, 30% by
      Clinical Nutrition staff and 26% by anthropometrical means. Incidence of
      malnutrition was low because the most common neoplasm among patients in the study
      was colorectal cancer. Oncologists tended to diagnose more cases of malnutrition
      due to a deficient training; nevertheless, SGA was useful because none of the
      malnourished patients was misdiagnosed and half of the well nourished patients
      were correctly identified as ones with no need for nutritional support.

PMID- 14682184
TI  - [Haematologic parameters in opiate addicts].
AB  - Levels of haemoglobin, haematocrit, number of red cells and leukocytes,
      haematological index (MCV, MCH, MCHC, DEI, MPV), sedimentation rate, iron,
      parameter related to accumulation and transport of iron (transferrin, ferritin,
      iron binding capability, transferring saturation index) and platelets were
      determined in blood samples of opiate addicts and they were compared with these
      results obtained in a control group. For both sexes, the levels of haemoglobin,
      haematocrit, iron and platelets were similar in the control groups and opiate
      addicts. Opiate addicts females presented a number of red cells and platelets
      higher and lower respectively than the correspond values of the control group.
      The haematological index in opiate addicts were higher than the values in the
      control groups for overall and considering males and females independently. The
      levels of ferritin in opiate addicts males were higher than these levels found in
      control groups, occurring the contrary in the females. Opiate addicts males and
      females included in the methadone maintenance treatment program (MMTP) presented
      similar values of haemoglobin, haematocrit, number of red cells and leukocytes
      than the corresponding opiate addicts non-included in MMTP, except opiate addicts
      males, who showed lower haematocrit values.

PMID- 14682185
TI  - [Bone remodeling].
AB  - The physiological maintenance of bone mass is ensured by bone tissue renewal,
      allowing old bone tissue to be replaced by an equivalent mass of bone matrix.
      After mechanical or hormonal stress activation, a phase of resorption by
      osteoclasts occurs, followed by a phase of bone formation by osteoblasts. Among
      the multiple factors involved in osteoblastic differentiation are the following:
      Cbfa1 (transcription factor); low density lipoprotein receptor-related protein-5
      (LRP-5), a membrane lipoprotein receptor and protein Wnt co-receptor, which plays
      an important role during development. It is possible that osteoblastic
      proliferation and differentiation are regulated by distinct pathways.
      Osteoclastic differentiation is also regulated by numerous factors:
      osteoprotegerin (OPG); RANK-L (receptor activator of nuclear factor kappa B
      ligand, a transmembrane protein related to tumour necrosis factor [TNF], the
      binding of which to its RANK receptor induces osteoclastic differentiation); and
      soluble TNF receptors. Local regulation of the OPG/RANK-L ratio could explain
      postmenopausal loss of bone mass. OPG could play a major role in myeloma and
      Paget disease. Osteolysis together with bone metastasis could also be related to
      the local production of RANK-L. OPG decreases osteolysis and offers an
      interesting therapeutic perspective for the treatment of osteoporosis and other
      diseases associated with bone hyper-resorption.

PMID- 14682186
TI  - [Pharmacology of the extracellular calcium ion receptor].
AB  - The calcium sensing receptor (CaSR) belongs to family 3 of G-protein coupled
      receptors. The CaSR, expressed at the surface of the parathyroid cells, controls
      parathyroid hormone (PTH) secretion and is the main regulator of calcium
      homeostasis. Its activity is regulated by small changes in the physiological
      concentrations of calcium and magnesium ions present in the serum and
      extracellular fluids, leading to the stimulation of the phospholipases C and A2.
      Molecules that potentiate the effect of extracellular calcium are called
      calcimimetics. They reduce the PTH level in vivo and have been proposed to be of
      therapeutic benefit for the treatment of both primary and secondary
      hyperparathyroidism. The blocking of CaSR by a calcilytic molecule results in the
      increase in serum PTH and might be of interest in the treatment of osteoporosis.
      The CaSR is also expressed in the thyroid, kidney, bone and in neuronal and glial
      cell populations, where it should be involved in the complex responses associated
      with calcium and magnesium ions present in the extracellular fluids.

PMID- 14682187
TI  - [Determining factors of bone mechanical resistance].
AB  - Bone strength is determined by bone geometry, cortical thickness and porosity,
      trabecular bone morphology and the intrinsic properties of bony tissue. The major
      complication of osteoporosis, i.e. fracture, is due to a lower bone strength.
      Thus, any treatment of osteoporosis implies an improvement in bone strength. Bone
      strength is indirectly estimated by bone mineral density (BMD) using Dual-Energy
      X-ray Absorptiometry (DXA). Since, DXA-measured BMD accounts for part of the
      variance in bone strength, some important factors are not captured by DXA, in
      terms of the effects of anti-osteoporotic treatment and the progression of
      osteoporosis. Geometry and trabecular microarchitecture have also to be taken
      into account. Thus, the assessment of the intrinsic mechanical quality of bony
      tissue should provide a better understanding of the role of tissue quality in
      determining bone strength. The careful investigation of all the determinants of
      bone strength (bone tissue included) should be considered in the pathophysiology
      of osteoporosis and in the mechanisms of action of anti-osteoporotic drugs.

PMID- 14682188
TI  - [Bone mineralization and mineral status].
AB  - After initial calcification in matrix vesicles or collagen fibrils, bones are
      continually modified by modelling then remodelling. In bone tissue, the degree of
      mineralisation of bone structural units is heterogeneous, reflects the rate of
      bone remodelling, and can be measured using microradiography. Our model is based
      on the fact that bone remodelling activity and thus the duration of the secondary
      mineralisation of bone tissue would influence its mineral status (mainly its
      degree of mineralisation or bone density at tissue level). When the bone
      remodelling rate increases (menopause, parathyroid hormone), the degree of
      mineralisation of bone tissue decreases. Conversely, after a diminution of the
      remodelling rate induced by antiresorptive treatments, the degree of
      mineralisation of bone tissue increases. Strontium ranelate (PROTELOS) has been
      tested to date as a potential therapeutic agent in patients suffering from
      postmenopausal osteoporosis. Recent phase III studies (the Spinal Osteoporosis
      Therapeutic Intervention [SOTI] study and the TReatment Of Peripheral
      Osteoporosis Study [TROPOS]) show a decrease in the vertebral and extravertebral
      fracture risk and an increase in bone mineral density measured at lumbar spine
      and femoral levels. Strontium ranelate has a unique mechanism of action, since it
      decreases bone resorption and increases bone formation ('decoupling' agent). Our
      preliminary observations in animal and man reveal that, because of this dual
      mechanism of action, the degree of mineralisation of bone tissue and the crystal
      characteristics of bone mineral are maintained at normal levels. More generally,
      these data indicate that the mineral status of bone tissue should be
      systematically taken into account during histomorphometric studies of bone.

PMID- 14682190
TI  - [Guidelines for the development of anti-osteoporosis medications].
AB  - Osteoporosis is a general disorder of the skeleton characterised by a decrease in
      bone mass, with damage to the microarchitecture leading to an increase in bone
      fragility and fracture risk. The incidence of this illness will increase in the
      future because of the aging of the population and increasing risk factors. Many
      guidelines have been proposed by qualified authorities--those of the European
      Agency for the Evaluation of Medicinal Products (EMEA) being the latest
      published. The aim of treatment of the osteoporosis is to increase, maintain or
      improve bone mass as well as its strength, with a view to decreasing the
      incidence of bone fractures. With regard to preclinical studies, in vitro studies
      -such as those using osteoblast or osteoclast cultures--allow a better
      understanding of the mechanism of action of drug treatment. The evaluation of
      bone quality should be performed in two species, such as the ovariectomised
      female rat model and larger animals (ewe, sow, primate etc.). Phase I studies are
      designed to enable determinations of pharmacokinetic profiles and bone diffusion
      and to offer indications of the putative clinical relevance of the dosages. For
      phase II studies (double-blind controlled studies versus placebo, ideally with a
      duration of 24 or sometimes 12 months), tests of three dosages are recommended,
      and the bone mass is considered as a relevant substitution criterion. The aim of
      secondary osteoporosis prevention studies (randomised double-blind and
      comparative controlled design versus placebo) is to avoid the occurrence of new
      bone fractures, and the main evaluation criterion is the number of patients with
      new fractures. The study length should not be less than 3 years. For evaluation
      of primary osteoporosis prevention, efficacy in the prevention of bone fracture
      is the prerequisite--before the use of bone mass as the main evaluation
      criterion. This criterion can be evaluated by alterations in bone mineral density
      at the rachis level. Reference drugs such as estrogens can be an alternative to
      placebo comparison. The tolerability of drugs for the treatment of osteoporosis
      requires evaluation in long-term studies and the collection of postmarketing
      data. The International Conference on Harmonisation (ICH) could lead to uniform
      guidelines for the US, Europe and Japan.

PMID- 14682191
TI  - [Impacts of the new flunitrazepam regulations on the consumption of hypnotics].
AB  - The frequent misuse of flunitrazepam has led the French drug agency (AFSSAPS
      [Agence francaise de securite sanitaire des produits de sante]) to subject this
      agent to the regulatory regime for drugs known to produce dependency; this drug
      may now be prescribed for no more than 14 days, is available only on an
      "ordonnance securisee" (prescribing and dispensing subject to stupefacient
      regulations), and pharmacists must dispense no more than 7 days' supply. We
      identified, in a French medical-care database, 738 patients who had received at
      least one flunitrazepam prescription in January 2001, and monitored the hypnotics
      delivered to this cohort over a period of 8 months. Sixty-nine percent of the
      patients had replaced flunitrazepam by another hypnotic without any further
      change. The most surprising result of our survey was the discovery that nearly
      half of the selected patients stopped using hypnotics during the review period.
      Although many hypotheses can be offered to account for this phenomenon, it seems
      that many consumers halted their consumption of flunitrazepam as a result of the
      new regulatory regime.

PMID- 14682189
TI  - [Large clinical trials for osteoporosis].
AB  - The prevention and treatment of osteoporosis are now a necessary goal because of
      the aging of the population and the social and economic costs of fracture
      complications. The publication of guidelines by registration agencies during the
      last 10 years has provided precise rules for evaluating new drugs designed for
      the prevention and treatment of postmenopausal osteoporosis. The benefit of
      combination treatment with calcium and vitamin D in osteoporotic patients has
      clearly been proven, especially among the oldest patients, but results of
      prospective studies designed for the prevention of fracture risk are conflicting.
      In the Fracture Intervention Trial (FIT), treatment with alendronate 10 mg/day
      reduces the risk of vertebral fracture by 48% and increases bone mineral density
      (BMD) in patients with vertebral fractures. In the Vertebral Efficacy with
      Risedronate Therapy Multi-National (VERT-MN) and VERT-NA (North America) studies,
      treatment with risedronate 5 mg/day reduces the risk of vertebral fracture by 49%
      and 41%, respectively. Risedronate 5 mg daly for 3 years leads to an increase in
      BMD. The Prevent Recurrence Of Osteoporotic Fractures (PROOF) study has shown a
      significant decrease in the risk of vertebral fracture in patients treated with
      calcitonin 200 IU. However, numerous criticisms of the methodology of this study
      design have been identified. Selective estrogen receptor modulators could act as
      agonists or antagonists of estrogens, depending on the target tissue. In the
      Multiple Outcomes of Raloxifene Evaluation (MORE) study, treatment with
      raloxifene reduces the risk of vertebral fracture by 50% in patients without
      prevalent vertebral fracture and by 30% in patients with prevalent vertebral
      fracture. PTH treatment leads to an increase in BMD and reduces the risk of
      vertebral fracture by 65%. Strontium ranelate has a novel mechanism of action
      (stimulation of bone synthesis and decrease in bone resorption), and
      administration of 2 g daily has a proven positive effect, leading to an increase
      in bone mass among women with osteoporosis. This effect was especially evident in
      the Spinal Osteoporosis Therapeutic Intervention phase III (SOTI) study, in which
      a significant decrease in the incidence of vertebral fracture of 41% over 3 years
      has been shown. Thus, effective therapeutic strategies now enable improved
      treatment of postmenopausal osteoporosis. However, this condition is still poorly
      diagnosed and not all patients are correctly treated. Preventing the occurrence
      of the first fracture should remain the prime concern.

PMID- 14682192
TI  - [Outpatient use of heparin: data from the Midi-Pyrenes Health Fund].
AB  - The risk of haemorrhagic complications associated with heparin therapy can be
      reduced by good clinical practice. The aim of this study was to describe
      outpatient heparin therapy by using the database of the National Health Fund. The
      study population consisted of affiliates of the salaried employees insured by the
      health fund branch of the Midi-Pyrenees region, and corresponded to 62% of the
      residents of that region. Analysis of treatments and biological monitoring was
      carried out on a 1-year period. During this period, 16,462 patients started a
      treatment with heparin, 92% for a single treatment. The mean age of the patients
      was 55 years (SD = 19.8) and the majority were women (53%). Nine percent of these
      patients were switched to oral anticoagulant therapy. Of the other patients, 52%
      received heparin for less than 10 days, 36% for between 10 days and 5 weeks, and
      12% for more than 5 weeks; 33% of the last group where heparin was prescribed for
      more than 5 weeks corresponds to a prescription of more than 3 months. Seventy
      three percent of the heparin treatment durations complied with the authorities'
      (l'Agence francaise de securite sanitaire des produits de sante [AFSSAPS])
      recommendations. Biological monitoring comprised a platelet count, an APTT
      (activated partial thromboplastin time) or an anti-Xa check in 41.9%, 27.8% and
      3.1% of treated patients, respectively. Creatininaemia was measured in 27% of
      patients aged > 75 years (a group at increased risk of adverse drug reactions).
      Even considering some of the differences noted between the medical prescriptions
      and the reimbursement data of the health fund, results from this study allowed an
      evaluation of medical practices and suggests that monitoring of patients
      receiving heparin treatments remains insufficient, thus decreasing the
      benefit/risk ratio of such therapies.

PMID- 14682193
TI  - Protective effect of Sesbania grandiflora against erythromycin estolate-induced
      hepatotoxicity.
AB  - Sesbania grandiflora, commonly known as 'sesbania', is widely used in Indian folk
      medicine for the treatment of liver disorders. Oral administration of an
      ethanolic extract of S. grandiflora leaves (200 mg/kg/day) for 15 days produced
      significant hepatoprotection against erythromycin estolate (800 mg/kg/day)
      induced hepatotoxicity in rats. The increased level of serum enzymes (aspartate
      transaminase, alanine transaminase, alkaline phosphatase), bilirubin,
      cholesterol, triglycerides, phospholipids, free fatty acids, plasma
      thiobarbituric acid reactive substances and hydroperoxides observed in rats
      treated with erythromycin estolate were significantly decreased in rats treated
      concomitantly with sesbania extract and erythromycin estolate. The sesbania
      extract also restored the depressed levels of antioxidants to near normal. The
      results of the study reveal that sesbania could afford a significant protective
      effect against erythromycin estolate-induced hepatotoxicity. The effect of
      sesbania was compared with that of silymarin, a reference hepatoprotective drug.

PMID- 14682194
TI  - [Consumption of "performance-enhancing" products by general practitioners].
AB  - The aim of this work was to test the hypothesis that doctors consume products to
      help them in their professional practice. A telephone survey was conducted over a
      12-month period among 402 general practitioners in France (using a 'quota
      method'). The 202 respondents consisted of 49 women and 153 men, with a mean age
      of 45.6 +/- 5.6 years. Nineteen percent of these respondents said that they had
      taken products to help with stress (11% had used benzodiazepines), 24% had used
      products to help with fatigue, 33% had used tobacco, and 20% said that they had
      experimented with cannabis. Finally, 44% of the respondents said that they had
      used products to 'hold out' during their studies--especially those presently
      taking products to assist with stress. Two questions must therefore be raised:
      (i) what is the impact of this addiction on the types of products prescribed by
      these doctors? and (ii) what steps are taken to prevent doctors from using such
      products and becoming addicted in the first place?

PMID- 14682195
TI  - [Preventing dependency in elderly persons: randomized study in the community].
AB  - The number of elderly people aged > 85 years will double by the year 2020.
      Helping the elderly to live independently at home is a major challenge for
      society. Physical exercise and protein energy intake might both be effective in
      preventing dependency. This paper describes the organisation of an ongoing study
      aimed at evaluating the preventive effect of such measures, involving 102 elderly
      persons randomised into two groups, one receiving preventive measures but not the
      other. The study organisation was based on representatives and selected workers
      from associations involved in home assistance for elderly. Their role consisted
      in recruiting persons for participation in the trial, encouraging them to perform
      exercises and take dietary supplements, and notifying the research team of all
      health-related events. This organisation has reached its objectives, even though
      the supervision of the domestic workers needs to be improved. This network,
      comprising stable workers (14 years of work experience on average in this study)
      offers the potential for future research in the community to evaluate preventive
      measures.

PMID- 14682196
TI  - [Retrospective analysis of adverse effects of infliximab in a hospital
      rheumatology service].
AB  - Infliximab is a chimeric monoclonal antibody against human tumour necrosis factor
      alpha (TNF alpha), and has received marketing authorization for the treatment of
      both rheumatoid arthritis (RA) and Crohn's disease. The aim of the present survey
      was to assess retrospectively adverse drug reactions (ADRs) in patients treated
      with infliximab for RA in a rheumatology department of the Toulouse University
      Hospital (Rangueil Hospital). Among 32 patients included in 2000 and 2001, 43
      "expected" ADRs occurred in 21 patients (65.6%) [mean age 51.4 +/- 14.0 years].
      In four patients (12.5%), ADRs were classified as "serious". In five other
      patients, they required the discontinuation of infliximab. We identified mainly
      infectious (n = 21), allergic (n = 3) and cardiovascular (n = 3) ADRs. Infectious
      ADRs were as follows: seven urinary infections, with a positive rechallenge (R+)
      in five; nine respiratory infections, with R+ in five; and five cutaneous
      infections. An acute rise in blood pressure occurred in three patients who had
      already been treated with antihypertensive drugs. The incidence of ADRs was as
      follows: respiratory 28.0%; urinary 22.0%; cutaneous 15.6%; allergic 9.4%; and
      cardiovascular 9.4%. In conclusion, our data allowed a quantitative and
      qualitative assessment of infliximab-induced ADRs. Further studies are required
      in order to improve knowledge regarding ADRs induced by long-term treatment with
      infliximab.

PMID- 14682197
TI  - [The myo-tendinopathy caused by levofloxacin].

PMID- 14682198
TI  - [Generalized angioedema with capillary leak syndrome after piroxicam use: a
      case].

PMID- 14682199
TI  - [Myocardial infarction after paclitaxel use].

PMID- 14682200
TI  - [Peritonitis after high-dose buprenorphine (Subutex) use: apropos of a case].

PMID- 14682201
TI  - [Tramadol and oral anticoagulants: interaction or confounding factors?].

PMID- 14682202
TI  - [Contribution of selected factors of inflammatory creative process in the
      vascular endothelial damage in the diabetes patients].
AB  - Diabetes causes the development of atherosclerotic vascular changes. Leukocytes,
      thrombocytes and also cytokines are involved in this process via endothelial
      activation. Estimation of interleukin 1 beta (IL-1 beta) and fibrinogen serum
      level of patients suffering from diabetes in context of endothelial damage is
      presented. The stage of vascular endothelium damage is based on the measurement
      of blood endothelial cells (EC) count and concentration of the plasmatic von
      Willebrand factor (vWF). Endothelial destruction level was established on the
      base of selectin L, P and E serum concentration. Activation of inflammatory
      proliferative mechanisms was indicated by IL-1 beta serum level. Serum
      haemostasis disorders were indicated by fibrinogen concentration. Patients with
      diabetes t. 1 and t. 2 differentiated by age and diabetes duration time with
      normal blood pressure and hypertension were included into the research. We showed
      that in both types of diabetes endothelium damage goes with significant increase
      of circulated EC count and vWF concentration. Increased serum level of IL-1 beta
      and fibrinogen in those patients shoulds significant correlation with vascular
      wall destruction, visibly marked in patients with diabetes t. 2.
      Hiperfibrinogenaemia and increased IL-1 beta concentration associate with
      significant engagement of SL and SE in inflammatory proliferative process of
      endothelium in young people suffering from diabetes t. 1 over 6 years.
      Hypertension coexisting with essential disease in both types of diabetes remains
      important progression factor in atheromatic vascular changes.

PMID- 14682204
TI  - [Red cell zinc protoporphyrin and its ratio to serum ferritin (ZPP/logSF index)
      in the detection of iron deficiency in patients with end-stage renal failure on
      hemodialysis].
AB  - Monitoring of iron metabolism has become a major clinical issue in end-stage
      renal patients undergoing hemodialysis. It can be done at three levels: storage,
      transport and marrow availability. The objective of that study was to evaluate if
      a combination of an iron storage marker, serum ferritin (SF) with red cell zinc
      protoporphyrin (ZPP), a marker of iron availability for erythron, will improve
      diagnostic value of both tests. In a baseline survey in the population of 186
      haemodialysis patients (75% treated with rHuEpo), the following parameters were
      determined: complete blood count, serum transferrin saturation (TSAT),
      transferrin, SF, hypochromic red cells % (HRC) and ZPP; the ZPP/logSF ratio was
      calculated. Iron deficiency was defined as a fernitin saturation--TSAT < 20%. In
      the second part of the study, 24 pts with SF < 50 ng/ml were given 50 mg of i.v.
      iron weekly for three months, then the same tests were repeated. During that time
      the doses of rhuEpo were stable. An increase in hemoglobin of > 1.0 g/dl was
      considered as a positive response. In 186 studied patients mean SF was 274 +/-
      335 ng/ml, and mean ZPP was 68 +/- 44 mumol/mol heme. A ZPP/logSF ratio > or = 40
      had the best combination of diagnostic sensitivity and specificity in detecting
      iron deficiency (76% and 83% vs: 56% and 89% for ZPP > 90 mumol/mol heme, 84% and
      34% for HRC > 5%, 68% and 58% for HRC > 10%) and the strong correlations with all
      other examined parameters were found. The index showed also the highest
      correlation with the response to the i.v. iron (r = 59; p < 0.01) of the tests
      evaluated. After three months the values of ZPP/logSF ratio decreased from 80 +/-
      105 to 39 +/- 19 (p < 0.01). A significant difference between responders and
      nonresponders was found for basal ZPP/logSF (p < 0.05) but not for ZPP. Our data
      suggest that the ZPP/logSF index provides a new valuable parameter for the
      identification of hemodialysis patients with iron deficiency and the prediction
      an erythropoietic response to iron supplementation.

PMID- 14682203
TI  - [Evaluation of probability of bile duct stone presence by using of non-invasive
      procedures].
AB  - Precise evaluation of bile duct stones presence in particular moment, performed
      using the most non-invasive method, is important for the planning of optimal
      treatment. Not only simple imaging procedures (like conventional transabdominal
      ultrasound--US) but also more sophisticated imaging methods (CT or MRI) are
      frequently useless. The "gold standards" of bile duct stones diagnosis are still
      endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic
      sphincterotomy and surgical choledochotomy. However, the ERCP expose the patients
      to the risk of some serious complications. The aim of the study was to evaluate
      the diagnostic capabilities of patients case history data and non-invasive tests
      (such as biochemistry, ultrasound data) in order to establish a risk scale in
      cases suspected for common bile duct stones. The investigated group comprised of
      135 patients treated from January 1996 through March 1997 in the Department of
      Gastroenterology Silesian Medical Academy. In patients prospectively enrolled to
      the study case history and a set of blood biochemical examinations were
      completed. In following, US was performed. The verification of the biliary tree
      (done with ERCP with endoscopic sphincterotomy or surgical choledochotomy) was
      performed. Examiners (US, ERCP) were blind to the other results of a patient.
      Case history data, laboratory blood tests and US results were used to select
      parameters significantly differing between patients with and without bile duct
      stones. Thirteen parameters were tested using Mann-Whitney's and chi 2 tests and
      four parameters were finally selected. For every selected parameter cut off
      values (i.e. values best differentiating patients with and without stones) were
      chosen on the basis of the chi 2 value, 95% confidence interval of risk ratio and
      Youden's index (gamma-GTP, alanine transaminase, enlarged bile ducts on US, bile
      duct stones on US). In the next step a set of different combinations of selected
      parameters was tested to find out the best waged scale for bile duct stones risk
      diagnosis. Finally, diagnostic efficacy of the best constructed scales and US
      alone were compared. Constructed risk scales can not be employed in the primary
      selection of patients, as their positive predictive value is quite high, but
      negative predictive value is low. US is also not valuable in evaluation of
      patients suspected for common bile duct stones.

PMID- 14682205
TI  - [The role of diagnostic tests in the identification of Chlamydia trachomatis
      infection in reactive arthritis].
AB  - Reactive arthritis (ReA) is a sterile inflammation of the synovial membrane of
      one or more joints developing after urogenital or gastro-intestinal infection.
      The syndrome most frequently follows infection with Chlamydia trachomatis. Useful
      for the diagnosis can be the serological tests. At present there is the
      possibility to identify the specific antibodies (IgG, IgA, IgM) to Chlamydia
      trachomatis. The subject of the study was the group of 87 patients in age 19-78;
      58 women and 29 men from whom urogenital smear and serum were tested. The control
      group were 30 people age 25-70 without rheumatological disorders. Chlamydia
      trachomatis was found in urogenital smear in 42 (48%), in 56 (64%) patients
      immunoglobulin IgG were positive, and immunoglobulin IgA in 16 (18%). The
      laboratory tests and clinical symptoms allow to make a diagnosis of ReA in 38
      (43%) and possible ReA in 5 (5.7%) of patients. CONCLUSIONS: 1. There is no gold
      standard for the diagnosis of ReA. 2. None of the tests or the clinical symptoms
      alone are strong enough to make a definite diagnosis of ReA. 3. Tests to identify
      Chlamydia trachomatis, with respect of typical clinical symptoms are useful the
      diagnosis of ReA. 4. The diagnosis of ReA is most probable if we have typical
      clinical symptoms, clinical evidence of a preceding infection plus a positive
      result of serology or PCR plus positivity for HLA-B27.

PMID- 14682206
TI  - [Expression of serum vascular endothelial growth factor correlates with clinical
      outcome in multiple myeloma].
AB  - A total of 34 multiple myeloma (MM) patients (17 recently diagnosed and 17 in
      progression of the disease) treated at the Department of Haematology, Blood
      Neoplasms and Bone Marrow Transplantation Medical University in Wroclaw were
      studied. Among the 19 females and 15 males, aged 31-72 years, there were 17 IgG,
      9 IgA and 1 IgM, one with plasma cell leukaemia and 6 with light chain disease.
      Staging according to Durie and Salmon disclosed: 7--IIA stage, 15--IIIA and 12-
      IIIB. Blood hyperviscosity symptoms (HS) developed in 9 patients, and precomatic
      state or coma was observed in four of them. Control group was constituted of 14
      healthy subjects--10 women and 4 men aged 32-51 years. Vascular endothelial
      growth factor (VEGF) serum concentration in MM patients varied from 0 pg/ml to
      760 pg/ml, mean 148.75 pg/ml, SD = 204.4 and in controls 0 pg/ml--164 pg/ml, mean
      31.5, SD = 23.3; p < 0.05. The mean VEGF level in recently diagnosed patients was
      higher than in progression of the disease, mean 188.6 pg/ml, SD = 230.6 and mean
      110.9 pg/ml, SD = 177.9; respectively, but the difference was not statistically
      significant. The patients with stage III had significantly (p < 0.05) higher VEGF
      level than those in stage II (mean 303.1 pg/ml, SD = 302.2 and mean 89.0 pg/ml SD
      = 121.6) respectively. The group of MM patients with renal failure (creatinine
      level > 2 mg%) had higher VEGF level than those with normal renal function: mean
      199.9 pg/ml, SD = 235, and mean 46.9 SD = 47 respectively, p < 0.01. Elevated
      VEGF level was also present in comatic and precomatic patients when compared with
      hyperviscosity patients without these symptoms (p < 0.05). In multiple myeloma
      patients no correlation was found between the serum VEGF level and percentage of
      bone marrow plasma cells, serum beta-2-m and monoclonal Ig levels, levels of Hb,
      albumine and LDH. Median survival time (M-ST) of patients with VEGF higher than
      71, 0 pg/ml was 32 months, M-ST of patients with VEGF below 71 pg/ml was 52
      months. In summary: serum level of VEGF in advanced state of multiple myeloma was
      elevated and correlated with clinical state. An elevated serum level of VEGF is
      associated with a poor prognosis.

PMID- 14682208
TI  - [Reasons for hospitalization in patients with chronic obstructive pulmonary
      disease(COPD)].
AB  - Reasons for cohort of patients with COPD hospitalisation in a 90-bed internal
      diseases ward within the 1st January and 31st December 2001 are discussed. Four
      hundred ten medical histories of COPD patients were analysed. The number of
      hospitalizations and the number of patients were distinguished. The majority of
      findings have been related to the number of hospitalizations. Percentage of COPD
      patients, spirometries and history of smoking have been related to the number of
      patients. In 12 months, the total number of hospitalizations has been 3,352,
      including 452 hospitalizations of COPD patients--13.8%. 2,731 patients, including
      333 COPD (12.2%) patients, have been hospitalised once or more times. Analysed
      group included 1,975 female (58.9%) and 1,377 male patients (41.1%), and 225
      female (49.8%) and 227 male patients (50.2%) in the COPD group. Average age was
      64.8 +/- 16.3 years (men--61.7 +/- 16.4 and women--67.0 +/- 15.8), while average
      age of COPD patients was 68.8 +/- 10.4 years (men--68.6 +/- 10.2 and women--69.0
      +/- 10.7). Average hospitalisation duration was 9.0 +/- 5.7 days, while for COPD
      patients--10.5 +/- 6.0 days. In this cohort COPD has been the main diagnosis in
      the 195 hospitalizations. Severity of the disease has been graded according to
      GOLD and the Polish Phtisiopneumonological Society recommendations. A structure
      of deaths in COPD group, treatment and history of smoking were analysed.

PMID- 14682207
TI  - [Assessment of blood superoxide dismutase, glutathione peroxidase activity and
      malondialdehyde concentration as oxidation status parameters in obese women].
AB  - Obesity is accompanied by a high incidence of atherosclerosis, arterial
      hypertension and non-insulin dependent diabetes mellitus in the pathogenesis of
      which is associated with oxygen-derived free radicals. The aim of the study was
      to compare blood oxidation status in obese women without coexisting diseases and
      in healthy women with normal body mass index (BMI). Studies were performed in 29
      premenopausal obese (BMI 35.79 +/- 4.62 kg/m2) and 31 lean (BMI 22.29 +/- 1.05
      kg/m2) women. Plasma lipid profile, activities of antioxidant enzymes:
      copper/zinc (Cu/ZnSOD) and manganese-containing superoxide dismutase (MnSOD) and
      glutathione peroxidase (GSH-Px), as well as concentrations of malondialdehyde
      (MDA)--a product of lipid peroxidation, were examined. In obese women there were
      significantly higher concentrations of total cholesterol (5.02 +/- 0.83 vs. 4.15
      +/- 0.43 mmol/l; p < 0.05), LDL-cholesterol (3.12 +/- 0.90 vs. 2.35 +/- 0.42
      mmol/l; p < 0.05) and triglycerides (1.72 +/- 0.85 vs. 1.02 +/- 0.18 mmol/l; p <
      0.01), while HDL-cholesterol level was lower (1.01 +/- 0.16 vs. 1.25 +/- 0.2
      mmol/l; p < 0.05). Moreover, in comparison to the control group, obese women
      showed increased activities of plasma MnSOD (6.72 +/- 1.43 vs. 4.99 +/- 0.58
      NU/ml; p < 0.05) and erythrocyte GSH-Px (35.38 +/- 10.31 vs. 19.15 +/- 7.12 mumol
      NADPH2/g Hb/min; p < 0.001), and concentrations of plasma MDA (2.93 +/- 0.53 vs.
      2.16 +/- 0.31 mumol/l; p < 0.05) and erythrocyte MDA (2.24 +/- 0.30 vs. 1.59 +/-
      0.36 mumol/g Hb; p < < 0.001). There were no differences between the two groups
      in activities of plasma and erythrocyte Cu/ZnSOD. In conclusion, the results
      demonstrate disturbances in oxidation status in premenopausal obese women with
      abnormal lipid profile, which may indicate the association between oxygen-derived
      free radicals and the increase in the incidence of obesity-related diseases.

PMID- 14682209
TI  - [DHR brachytherapy as palliative treatment of advanced lung cancer in patients
      treated previously on another cancer].
AB  - PURPOSE: To analyze treatment results of palliative HDR brachytherapy in patients
      with advanced lung cancer treated previously on another cancer. From May 1999 to
      May 2001 24 patients with diagnosis of lung cancer were treated with HDR
      brachytherapy in Greatpoland Cancer Center. All patients were treated for another
      cancer in the past. All patients became disqualified from surgical treatment and
      radical radiotherapy due to advance stage of diseases. High dose brachytherapy of
      22.5 Gy counted in distances 1 cm from tube axis was used. Control group
      consisted of 56 lung cancer patients without past history of another malignancy
      treated with brachytherapy in the same period. Patients were observed during a
      period of 12 months in terms of local remission rates and survival time depends
      on chosen clinical factors. Median survival time in the first group of patients
      was 5.6 months and 8.9 months in the control group. Patients with the history of
      prior cancer lived shorter (log-rank test, p = 0.003). Significant correlation
      was observed between survival rate and remission rate achieved in 1th month after
      the end of treatment (log-rank test, p = 0.001). CONCLUSIONS: 1. Past history of
      cancer decreases survival of patients with advanced lung cancer treated
      palliatively with HDR brachytherapy. 2. HDR brachytherapy of advanced lung cancer
      provides improvement of dyspnoea in most of patients. 3. The most important
      prognostic factor for survival was remission achieved within 1th month after the
      end of brachytherapy.

PMID- 14682210
TI  - [Sarcoidosis recognized since early childhood in the 18-year-old patient. Case
      report].

PMID- 14682211
TI  - [Osteitis as a symptom of SAPHO syndrome].
AB  - SAPHO syndrome is an acronym given to a spectrum of diseases with the following
      features: synovitis, acne, pustulosis, hyperostosis and osteitis. The main
      problem of the differential diagnosis in 3 cases presented in our paper was the
      aseptic osteitis.

PMID- 14682212
TI  - [Paget's disease].

PMID- 14682213
TI  - [The role of adhesion molecules in the pathophysiology of diseases: therapeutic
      prospects].

PMID- 14682215
TI  - [Air pollution and lung function].

PMID- 14682214
TI  - [The involvement of coagulation in inflammatory lung diseases].

PMID- 14682216
TI  - [Amyloidosis in the course of rheumatic disease: pathogenesis, incidence,
      clinical aspects and diagnosis].

PMID- 14682217
TI  - [Treatment and prognosis of secondary amyloidosis in the course of rheumatic
      disease].

PMID- 14682218
TI  - [Subpopulation of lymphocytes Th1 and Th2 in hematologic system].

PMID- 14682219
TI  - [The influence of habitual cigarette smoking on level of endogenic histamine
      determined simultaneously in plasma, gastric juice and gastric mucosa in healthy
      individual].
AB  - The aim of this study was to examine the amount of endogenic histamine measured
      simultaneously in the plasma, gastric juice and gastric mucosa in habitual
      smokers and nonsmokers and to suggest possible implications of the obtained
      results. METHODS: 48 individuals were selected for this test. None of them
      suffered from any symptoms of ulcer disease. 28 were habitual cigarette smokers,
      20 were nonsmokers who had never smoked. The tests were carried out standard
      conditions. Each patient underwent endoscopy. Gastric juice was taken by catheter
      via endoscopes, and biopsy specimens were taken for microscopic examination and
      establish histamine levels, which were also measured in plasma. Blood samples
      were taken before endoscopy. RESULTS: The levels of endogenic histamine in plasma
      and gastric juice were significantly higher in habitual smokers than in
      nonsmokers, especially in plasma. In the tissue of both groups no statistically
      significant differences were observed, but the histamine level was slightly
      higher in nonsmokers. CONCLUSION: The amount of histamine in plasma, as well in
      gastric juice, is may be connected with habitual cigarette smoking, and its level
      in tissue may also depend on smoking.

PMID- 14682220
TI  - [Myoglobin and troponin I as markers of myocardial damage during cardioversion of
      atrial fibrillation].
AB  - We performed direct comparison of safety and efficacy of monophasic and biphasic
      shock cardioversion (CV) of atrial fibrillation (AF). Troponin I (cTnl) and
      myoglobin (My) were used as markers of potential myocardial and skeletal muscle
      damage during the procedure. METHODS: 63 patients (p.t.s.) with persistent,
      nonvalvular AF (F/M 18/45; mean age 61.6 +/- 11.4 years) were randomized to CV
      either with monophasic (F/M 10/24, Group I) or biphasic (F/M 8/21, Group II)
      shock. Plasma levels of cTnl and My were measured before CV, 6 hours and 24 hours
      after CV. RESULTS: The efficacy of CV was significantly higher in Group II (93%
      vs 85%, p < 0.04). Sinus rhythm restoration required lower total energy used
      during procedure with biphasic shock (379.8 +/- 301.5 vs 192.8 +/- 100.6 J; p
      0.001). There was no significant difference in mean values of cTnl before CV in
      both groups (0.3 +/- 0.2 vs 0.2 +/- 0.1 ng/mL, p > 0.15). In 14 pts (41%) from
      Group I and 3 pts (10%) from Group II plasma cTnl concentration above
      discriminatory level (0.9 ng/mL) were noted. There was a significant increase in
      mean plasma cTnl level (0.3 +/- 0.2 vs 1.9 +/- 0.9 ng/mL, p < 0.04) 24 hours
      after the procedure in Group I. We did not observed significant differences in
      cTnl plasma concentration 6 and 24 hours after CV in Group II (0.2 +/- 0.1 vs 0.4
      +/- 0.2 ng/mL, p > 0.15). Both study groups did not significantly differ in mean
      serum My level at baseline (39.1 +/- 14.2 vs 43.1 +/- 20.9 ng/mL). In Group I
      mean My serum concentration increased during the first 6 hours after CV (43.1 +/-
      20.9 vs 247.9 +/- 53.3 ng/mL, p < 0.02) and there was a significant decreasing in
      My serum level during the further observation (247.9 +/- 53.3 vs 104.5 +/- 46.1
      ng/mL, p < 0.03). Mean serum My concentration remained within normal ranges
      during the 24 hour follow-up after the biphasic shock CV (43.1 +/- 20.9 vs 43.6
      +/- 29.1 ng/mL). Increased of cTnl and My in Group I may be due to myocardial and
      skeletal muscle damage and correlate closely with cumulative energy delivered
      (Spearmann correlation index (r) = 0.55, p < 0.01 for My and r = 0.66, p < 0.01
      for cTnl). In Group I positive correlation between cumulative energy used during
      CV and increase of studied markers indexed with left ventricular mass (r = 0.6, p
      < 0.05 for My and r = 0.74, p < 0.04 for cTnl) was observed. There was no
      significant correlation between delivered energy and increase of heart markers in
      Group II noted. CONCLUSIONS: We observed the significant increase in mean serum
      cTnl and My level 24 hours after CV with monophasic shock and its positive
      correlation with total energy used during the procedure. There is a conclusion
      that biphasic shock used during CV of AF is more efficient and may cause less
      myocardial and skeletal muscle damage due to lower energy delivered.

PMID- 14682221
TI  - [The influence of hyperthyroidism on selected parameters of oxidant-antioxidant
      balance on animal model].
AB  - The aim of the experiment was to examine the influence of increased concentration
      of thyroid hormones on selected parameters of oxidant-antioxidant balance through
      the analysis of the antioxidant enzymes activity, the content of antioxidant
      vitamins, and the concentration of the unsaturated fatty acids peroxidation
      (TBARS). Administration of levothyroxine of the dose 100 micrograms/kg of body
      mass to rabbits for 21 days caused the increase of TBARS concentration, the
      decrease of concentration of vitamins C and E, and the increase of SOD activity.

PMID- 14682222
TI  - [Thrombin activatable fibrinolysis o inhibitor-TAFI- in dialyzed patients with
      diabetic nephropathy].
AB  - Patients with end-stage renal disease dialyzed due to diabetic nephropathy are at
      higher risk of death due to cardiovascular complications than dialyzed non
      diabetic patients. Disturbances in hemostasis may play a role in the vascular
      complications of diabetes mellitus. It has been postulated that TAFI-Thrombin
      Activatable Fibrinolysis Inhibitor, newly described glycoprotein, couples two
      opposite systems: coagulation and fibrinolysis. The aim of the work was to study
      TAFI concentration in hemodialyzed and peritoneally dialyzed diabetic and non
      diabetic patients. We assessed: TAFI concentration, markers of ongoing
      coagulation: thrombin-antithrombin complexes, prothrombin fragments 1 + 2
      (markers of TAFI activation), a marker of ongoing fibrinolysis: plasmin
      antiplasmin complexes, a marker of TAFI cataliser to TAFIa-thrombomodulin using
      commercially available kits. All four groups studied did not differ in regard to
      fibrinogen, thrombomodulin, plasmin-antiplasmin complexes, and TAFI
      concentration. Both groups of dialyzed diabetic patients have higher
      concentration of markers of ongoing coagulation when compared to dialyzed non
      diabetic patients. Hypercoagulable state observed in dialyzed diabetic patients
      may contribute to the higher cardiovascular mortality in these population.

PMID- 14682223
TI  - [Urinary leukotriene E4 concentration in patients with bronchial asthma and
      intolerance of non-steroids anti-inflammatory drugs before and after oral aspirin
      challenge].
AB  - BACKGROUND: Leukotrienes (LTC4, LTD4, LTE4) belong to eicosanoids and they play
      important role in allergic inflammation. Leukotrienes are 5-lipooxygenaze
      products of arachinoid acid. It is known that concentration of LTE4 increases in
      patients with bronchial asthma, after some allergy provocation and in patients
      with bronchial asthma and intolerance of on steroids anti-inflammatory drugs. The
      aim of the study was estimated the urinary concentration of LTE4 in patients with
      bronchial asthma and intolerance of no steroids anti-inflammatory drugs. MATERIAL
      AND METHODS: The study group consisted of 21 patients with asthma and intolerance
      of non steroids antiinflammatory drugs (F 19, M 2) in age from 21 to 72 years old
      (mean = 49 +/- 14), with middle time of asthma duration mean = 13.4 +/- 12.9
      years In study group 11 person had positive skin test, 7 nasal polyps, and 8
      person positive family history of bronchial asthma. After oral provocation
      aspirin challenge in 5 subjects' aspirin induced asthma was confirmed, 3 persons
      were not qualified to test. Urinary concentration of LTE4 before and 24 h after
      aspirin provocation was analyzed in all the patients. Leukotriene were detected
      by enzymatic Leukotriene E4, EIA Kit, Cayman Chemical test. RESULTS: In group of
      patients with aspirin asthma basic concentration of LTE4 was 416.6 +/- 374.4
      pg/mL, and after provocation 496.6 +/- 485.3 pg/mL, in the group without
      sensitivity to aspirin appropriate 262.9 +/- 404.0 vs 261.2 +/- 259.66 pg/mL, and
      in the group disqualified to test 181.6 +/- 55.75 pg/mL. CONCLUSION: 1 Patients
      with aspirin asthma have higher concentration of LTE4. 2. Excretion of LTE4 in
      patients with aspirin induced asthma raised after oral aspirin provocation and
      higher level was detected is til 24 hours after challenge. 3. This results
      confirmed the role of cysteinic leukotrienes in pathogenesis of aspirin induced
      asthma.

PMID- 14682224
TI  - [Renal tubular dysfunction in patients with rheumatoid arthritis starting with
      low dose of methotrexate].
AB  - BACKGROUND: The elevation of N-acetyl-beta-D-glucosaminidase (NAG) in urine has
      been shown to be associated with reversible renal tubular damage. OBJECTIVES: The
      aim of the study was to examine the effect of first oral low dose methotrexate
      (MTX) on urinary excretion of NAG comparing with MTX concentration in serum and
      urine in a cohort of patients with rheumatoid arthritis (RA). METHODS: Urinary
      NAG to urinary creatinine ratio (NAG index) determined in 43 patients (5 males,
      38 females) with RA who started taking the first oral dose of 10 mg of MTX.
      Urinary NAG index was observed at 24 h and 48 h after the first MTX dose. MTX
      concentration was measured in blood at 90 minutes and in blood and urine at 24 h
      after the drug administration. RESULTS: NAG-enzymuria was increased in 72.1% of
      the patients before administration of MTX therapy (10.8 UI/g creatinine). There
      was no change in NAG index at 24 and 48 h after first dose of MTX (9.1 and 10.7
      UI/g of creatinine). No differences of NAG-enzymuria in non-steroidal anti
      inflammatory drug (NSAID)-treated patients and NSAID-free patients before and
      after MTX administration were revealed. The patients with decreased creatinine
      clearance had before treatment higher NAG index than those with normal creatinine
      clearance but there was not any significant increase of NAG activity after first
      dose of MTX in the patients with decreased creatinine clearance. Continued
      treatment with MTX resulted in a decrease in NAG activity accompanied by serum C
      reactive protein concentration. CONCLUSION: The use of low dose MTX with or
      without NSAIDs does not influence the renal tubular function in patients with RA.

PMID- 14682225
TI  - [Autologous hematopoietic stem cell transplantation for the treatment of
      aggressive non-Hodgkin's lymphoma. The experience of Polish lymphoma research
      group].
AB  - We analysed the outcome of 200 patients, aged 38 (13-72) years, with aggressive
      non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy followed by
      autologous haematopoietic stem cell transplantation (autoHSCT) in ten
      oncohaematological centres belonging to Polish Lymphoma Research Group (PLRG).
      The source of stem cells for transplantation was peripheral blood (autoPBSCT, n =
      153), bone marrow (autoBMT, n = 40) or both blood and bone marrow (n = 7). The
      probability of overall survival (OS) and progression-free survival at 10 years
      was 51% (+/- 7%). The transplant-related mortality rate equalled 7%. In
      multivariate analysis, the only factor influencing independently the probability
      of OS was disease status at transplantation (p < 0.00001). The outcome of
      patients transplanted in first or subsequent complete remission or first partial
      remission (PR) was significantly better compared with subjects given autoHSCT in
      PR 2 or those with primary or secondary refractoriness. Regarding histological
      subtypes, the highest OS rate (87%) was observed for anaplastic large T cell
      lymphoma. The outcome after autoBMT was better compared with autoPBSCT (OS
      probability: 67% vs. 43%), although the difference did not reach statistical
      significance. We conclude that high-dose therapy followed by autoHSCT is an
      effective option for high-risk aggressive NHL. Remission status is a major factor
      determining long-term outcome. This should be taken into account when referring
      patients for autoHSCT.

PMID- 14682226
TI  - [Rate of liver fibrosis progression among patients with chronic hepatitis C in
      Poland].
AB  - AIM: To assess the rate of liver fibrosis (RLF) among previously untreated
      patients with chronic hepatitis C (CHC) and to identify predictors of rapid
      progression to cirrhosis in this group. PATIENTS AND METHODS: Medical records of
      337 consecutive patients with biopsy proven CHC (anti-HCV and HCVRNA positive;
      F/M: 153/184; mean age at biopsy: 43 +/- 14 years) and with known probable age at
      infection have been analysed. There were no intravenous drug users among the
      patients. HBsAg--and HIV-positive subjects as well as those with other
      concomitant liver disease were excluded from the analysis. The RLF was defined as
      the ratio between fibrosis stage (scored 0-6 units [U] according to Ishak's
      criteria, with 6 representing established cirrhosis) and the duration of HCV
      infection (in years). The RLF was analysed in relation to the age at infection,
      sex, route of transmission, alcohol abuse, past HBV infection, acute hepatitis
      history, HCV genotype and hepatic steatosis. Based on published data, a patient
      with RLF > or = 0.3 U/yr (cirrhosis up to 20 years after HCV infection) was
      arbitrarily defined as a rapid progressor. Both uni- and multivariate statistical
      analyses were performed. RESULTS: The mean RLF was 0.14 +/- 0.17 U/yr (range 0
      0.83) and the expected mean duration from infection to cirrhosis was 43 years. In
      multivariate analysis the only independent factors associated with an increase in
      RLF were the older age at infection and alcohol abuse (both with p < 0.0001). 58
      [17.2%] patients were rapid progressors and the same factors as mentioned above
      have been independent predictors of cirrhosis up to 20 years after infection.
      There were as much as 55.5% of rapid progressors among alcohol abusers infected
      in the age over 30 and only 1.9% among non-alcoholic patients infected in the age
      up to 30 years. CONCLUSIONS: Our study showed that natural course of CHC in
      Poland is similar to other regions of the world. HCV-related liver disease
      progression is accelerated among alcohol abusers and infected in older age. In
      contrast, risk of cirrhosis seems to be minimal among non-alcoholic patients
      infected before the age of 30.

PMID- 14682227
TI  - [Classic form of Bourneville-Pringle disease in a daughter and appearance of
      hypopigmented macules of her father's skin].
AB  - Tuberous sclerosis (Bourneville-Pringle disease) is an genetic autosomal dominant
      disease, but in over 50% cases there are new spontaneous mutations. During this
      disease visceral hamartomas do tend to develop in various tissues. Earlier it was
      considered that in order to set a diagnosis the knowledge of Vogt's triade was
      required (angiofibroma, epilepsia, mental retardation). But new not typical forms
      occur, that do not contain all the above mentioned three elements. The phenomenon
      is connected with the appearance of a new mutations of the gene or with a
      variable gene penetrance. In these study case we present a 21-year old patient
      who shows the fully blown symptoms of Vogt's triad and her father who only has
      hypopigmented macules on his back.

PMID- 14682228
TI  - [Acute painful neuropathy at the initial period of effective insulin therapy].
AB  - We report on three patients (two men with recently discovered type 1 diabetes and
      one woman with type 2 diabetes and secondary failure of oral antidiabetic drugs)
      who developed acute painful neuropathy after the institution of effective
      insulintherapy and rapid drop of glycemia. The EMG disclosed in them traits of
      mixed lesions of motor-sensory neurons at the level of nerve fibres, more evident
      in sensory nerves of low extremities. In one patient (A) observed for 5 years, in
      spite of progressive partial remission of clinical symptoms and signs, no
      improvement in successive EMG was found. The evident therapeutic effect of alpha
      lipoic acid in the presented cases needs to be confirmed in appropriate
      prospective studies.

PMID- 14682230
TI  - [Hyperhomocysteinaemia and its atherogenic effect in uremic patients].

PMID- 14682231
TI  - [Multidirectional effects of platelet-derived growth factor B on the kidney].

PMID- 14682229
TI  - [Immunosuppression followed by autologous hematopoietic stem cell transplantation
      for the treatment of severe systemic lupus erythematosus, systemic sclerosis and
      rheumatoid arthritis].

PMID- 14682233
TI  - [Unusual noninfectious complications of peritoneal dialysis].

PMID- 14682232
TI  - [Anti-citrulline antibodies in rheumatoid arthritis; diagnostic and prognostic
      values].

PMID- 14682234
TI  - [Nitric oxide in allergic diseases].

PMID- 14682235
TI  - [The response to the letter of Dr. Jerzy Durkalec regarding literature review by
      Przemyslaw Kotyla, Bogna Sliwinska-Kotyla and Eugeniusz J. Kucharz "The
      Significance of Chlamydia pneumoniae Infection in the Development of Sclerosis].

PMID- 14682236
TI  - Chromosomal location and expression of green fluorescent protein (gfp) gene in
      microspore derived transgenic barley (Hordeum vulgare L.).
AB  - Four doubled haploid barley lines (A, C, D, E) derived from gfp (green
      fluorescent protein) transformation and selection following particle bombardment
      of microspores were studied for gene expression pattern and the location of
      genome inserts. The integration sites were detected by fluorescence in situ
      hybridization (FISH) using the gfp plasmid DNA as a probe. Plants from events A,
      C, D and E all have a single insert site on chromosome 7L(5HL) at different
      locations while line E has a second insert site on chromosome 5S(7HS). All
      original transgenic plants were hemizygous for the transgenes and segregated in
      the T1 and T2 generations. Although line D had no GFP expression, FISH and PCR
      could detect gfp gene on its chromosome in transformed plants. Expression levels
      of GFP varied with lines and tissues examined. Plants from line C showed good
      expression in pollen and an intermediate level in root tips. Plants from A have
      intermediate expression of GFP in the pollen and light expression in the root
      tips. Line E showed strong expression in the root-tips and an intermediate level
      of GFP in the pollen. Lines A and C segregated as a single Mendelian locus while
      E segregated in a duplicate loci ratio (15:1) on seedling root tips but had low
      expression frequency in the pollen. PCR results were consistent with GFP
      expression on root tips in the three segregating lines. The expression of GFP for
      lines D and E was abnormal and may be related to the physical location of the
      transgene or the gene construct used.

PMID- 14682237
TI  - [Studies of genetic analysis and SSR linked marker location of gene resistance to
      southern rust in inbred line P25 of maize].
AB  - Using P25 (immune inbred line), F349 (susceptible inbred line) and the derived
      population F1, F2, B1 and B2 as materials, we investigated the heredity the of
      disease resistance gene to maize southern rust (Puccinia polysora Underw.)
      through the major-gene and polygene inheritance model. The results indicate that
      a major resistance gene exists in the inbred line P25 and expresses with additive
      effect. We didn't find any multi-genes. The inheritabilities of this major
      resistant gene among F2, B1 and B2 were 81.88%, 38.14% and 55.1%, respectively.
      We constructed a maize SSR linkage map using P25 x F349 F2:3 population, and
      located the resistant gene on chromosome 10. The genetic distance between this
      gene and phi059 marker was 5.8 cM.

PMID- 14682238
TI  - [Mapping quantitative trait loci associated with rice grain shape based on an
      indica/japonica backcross population].
AB  - Appearance of rice grain represents a major character of rice quality in many
      rice-producing areas of the world, especially in hybrid rice production in China.
      In this study, we conducted a molecular marker-based genetic analysis of the
      traits that are determinants of the appearance quality of rice grains, including
      grain length, grain width and grain shape (measured as grain length to grain
      width ratio). Two typical indica/japonica varieties Balilla and Nantehao(NTH)
      were selected to construct Balilla/NTH//Balilla backcross population containing
      142 individuals. In the population, grain length, grain width and grain shape all
      conform to the normal distribution with certain transgressive segregation. It can
      be deduced that all of three traits were controlled by some quantitative trait
      loci (QTLs). In order to explore the QTLs effect, number and location, a linkage
      map consisting of 108 SSR markers based on the backcross population was
      constructed, and QTLs mapping was carried out for grain length, grain width and
      grain shape. A QTL, qGL-12, was detected for grain length at the interval RM101
      RM270 on chromosome 12, its additive effect was 0.26 mm, and can explain 16.7%
      genetic variation. As for grain width trait, two QTLs were found, qGW-2 located
      at RM154-RM211 interval on chromosome 2, and qGW-3 at interval RM257-RM175 on
      chromosome 3, accounting for 11.5% and 16.6% genetic variation, respectively. The
      alleles at qGW-2 and qGW-3 from parent Balilla can increase grain width by 0.10
      mm and 0.12 mm. For grain shape, 3 QTLs, qLW-2, qLW-6 and qLW-7 were found,
      located on chromosome 2, 6, and 7, respectively. qLW-2 and qLW-7 had positive
      effect, and they can explain 12.7% and 18.3% genetic variation, while qLW-6 had
      negative effect and contributed 11.5% genetic variation to the backcross
      population. The prospects of application of linkage relationship between SSR
      marker and QTLs in marker based selection (MAS) in rice breeding, and the
      improvement of grain shape and rice appearance quality were discussed.

PMID- 14682239
TI  - [Construction of expression vector with BG2 gene and its transformation in
      wheat].
AB  - beta-1,3-glucanase(BG2) is one of the pathogensis-related-proteins(PR). Study of
      these proteins and their related genes is one of the hot points in plant genetic
      engineering of disease resistance for a long time. In this research, specific
      primers were designed with the enzyme cleavage site of Spe I in its forward one
      and Not I site in the backward according to the BG2 gene sequence. Using this
      pair of primers, BG2 gene, which was contained in the plasmid of pRTL2, was
      amplified and confirmed by sequencing the amplified fragment inserted into T-easy
      vector. The positive clone containing BG2 gene was digested with the enzymes of
      Spe I/Not I and then BG2 gene was inserted into the Xba I/Not I sites of super
      expression binary vector pATC940. The reconstructed expression vector named as
      pATCBG2 was introduced into the wheat of Longfumai10 and Longfumai3 (Triticum
      aestivum L. em. Thell) through the particle gun transformation method. The
      Kanamysin resistant (Km') transformants were obtained. PCR, Dot-blotting and PCR
      Southern hybridization analysis showed that the BG2 gene was integrated into the
      genome of wheat. Result of pathogen inoculation assay on the transgenic plants
      showed that the transgenic plants had a higher resistant disease score of 1-2
      grade than the control.

PMID- 14682240
TI  - [Cloning and identification of the priming glycosyltransferase gene involved in
      exopolysaccharide 139A biosynthesis in Streptomyces].
AB  - Recently in our laboratory, Streptomyces sp. 139 has been identified to produce a
      new exopolysaccharide designated EPS 139A that shows anti-rheumatic arthritis
      activity. The strategy of studying EPS 139A biosynthesis is to clone the key gene
      in the EPS biosynthesis pathway, i.e. the priming glycosyltransferase gene
      catalyzing the first step of nucleotide sugar transfer. Degenerate primers-based
      PCR approach was adopted to isolate the putative priming glycosyltransferase gene
      in Streptomyces sp. 139. According to the genes encoding the priming
      glycosyltransferases that have been identified in several microorganisms, a
      multiple alignment of the amino acid sequences of these genes was used to
      identify regions conserved between all genes. To clone the priming
      glycosyltransferase gene in Streptomyces sp. 139, degenerate primers were
      designed from these conserved regions taking into account information on
      Streptomyces codon usage to amplify an internal DNA fragment of this gene. A
      distinctive PCR product with the expected size of 0.3 kb was amplified from
      Streptomyces sp. 139 total genomic DNA. Sequence analysis showed that it is part
      of a putative priming glycosyltransferase gene and contains the predicted
      conserved domain B. To isolate the complete priming glycosyltransferase gene, a
      Streptomyces sp. 139 genomic library was constructed in the E. coli--Streptomyces
      shuttle vector pOJ446. Using the 0.3 kb PCR product of priming
      glycosyltransferase gene as a probe, 17 positive colonies were isolated by colony
      hybridization. A 4.0 kb BamHI fragment from all positive cosmids that hybridized
      to this probe was sequenced, which revealed the complete priming
      glycosyltransferase gene. The priming glycosyltransferase gene ste5 (GenBank
      under accession number AY131229) most likely begins with GTG, preceded by a
      probable ribosome binding site (RBS), GGGGA. It encodes a 492-amino-acid protein
      with molecular weight of 54 kDa and isoelectric point of 10.6. The G + C content
      of ste5 is 73%, close to the average of G + C content (74%) for Streptomyces.
      Moreover, the preference usage of G or C as third base of codons are found in the
      ste5, which is in accordance with the Streptomyces codon usage. A BlastP search
      showed that the C-terminal region of Ste5 shows highly homology with a number of
      priming glycosyltransferases from many different organisms. Ste5 contains two
      putative catalytic residues, Glu and Asp (residues 423 and 474) with a spacing of
      approximately 50 amino acids that conserved in various beta-glycosyltransferases.
      Moreover, the C-terminal one third of Ste5 contains three domains, A, B and C
      that is reported to be common to glycosyltransferases. By hydrophilicity plot
      prediction, the N-terminal two thirds of Ste5 exhibits 5 putative transmembrane
      domains. To investigate the involvement of the identified polysaccharide gene
      cluster in EPS 139A biosynthesis, the gene ste5 encoding priming
      glycosyltransferase was insertionally disrupted by a single-crossover homologous
      recombination event. A 0.85 kb internal fragment of ste5 was cloned into vector
      pKC1139 to yield pLY5015 that was transduced into Streptomyces sp. 139. Correct
      integration in Streptomyces LY1001 ste5- mutant strain was confirmed by Southern
      hybridization. After fermentation, no EPS 139A could be detected in the cultures
      of ste5- mutant strain Streptomyces LY1001. Therefore, the gene ste5 identified
      in this work is involved in the synthesis of the Streptomyces sp. 139 EPS.

PMID- 14682242
TI  - [Construction of insecticidal recombinant Bacillus thuringiensis using an
      integrative vector].
AB  - Insecticidal crystal protein gene cry1C which is highly toxic to Spodoptera
      exigua was cloned into an integrative vector pBMB-F7E, which was derived from
      Bacillus thuringiensis transposon Tn4430. The recombinant integrative plasmid
      pBMB-FLC harboring the cry1C gene was gained and transformed into a wild-type Bt
      strain YBT803-1. A transformant BMB803-A was obtained, and grown at 46 degrees C
      for about 120 generations, From which three recombinants with cry1C gene
      integrating into the chromosome were achieved at a frequency of approximately 3.4
      x 10(-5). Southern blotting revealed that the integration occurred in different
      sites of the chromosome. The integrated cry1C were expressed effectively. The
      results of bioassays showed that the toxicity of recombinants BMB803-X and BMB803
      Z against Plutella xylostella were similar to that of strain YBT803-1, and their
      toxicity to Spodoptera exigua were higher than that of strain YBT803-1.

PMID- 14682241
TI  - [Construction and verification of the effectiveness of pMBL: a cloning vector of
      exported proteins encoding genes].
AB  - The beta-lactamase was used as the reporter of expression and transmembrane
      secretion in this paper. A fragment of Amp resistance gene encoding the mature
      part of beta-lactamase (delta P delta SP Amp, i.e. without promoter and signal
      peptide coding sequences) was amplified from pUC18 vector. The upstream primer
      has BglII, BclI, BamHI in three reading frame respectively, in order to in frame
      fuse and express target genes together with the downstream reporter in finally
      constructed vector. Meanwhile, pET-28 was digested with the restriction enzymes
      BglII and Bst1107 I. The 2.8 kb fragment with replication origin, Kan resistance
      gene and MCS was recovered, filled, self-ligated and resulted in a plasmid pKan
      B. The Bgl II site on pKan-B was then filled and the plasmid pKan was obtained.
      The delta P delta SP Amp gene, which was first cloned into pGEM-T-EASY vector,
      was inserted into pKan between EcoR I and XbaI sites. A plasmid pMBL-E was
      selected, with which the bacteria host could grew on Kan plate but not on plate
      with both Amp and Kan. An EcoRI site beside HindIII on the plasmid pMBL-E was
      then filled, and the plasmid pMBL, a cloning vector of the exported proteins
      encoding genes was finally obtained. Both results of the restriction enzyme
      digestion and sequencing demonstrated the correctness of the construction. The
      Tet resistance gene, a transmemebrane protein encoding gene, was applied to
      verify the effectiveness of the reporter in the vector. Cut with EcoRI and BamHI,
      a 375 bp fragment including promoter and 96 animo acids coding sequence
      (including signal peptide) of Tet was obtained from pBR322 vector. The fragment
      was then ligated to the vector pMBL which had been cut with both enzymes of EcoRI
      and BglI, or EcoRI and BclI, or EcoRI and BamHI (as 0, +1, +2 respectively of the
      beta-lactamase gene reading frame). Kan and Amp double resistant colonies only
      grew with the EcoRI and BglII combination (0 position). Restriction enzyme
      digestion and sequencing results of the recombinant plasmid showed that Tet
      resistance gene, which promoted the expression and transmembrane secretion of
      downstream beta-lactamase, was inserted in a correct reading frame into the
      vector. Thus, the results verified the effectiveness of the constructed vector
      pMBL, which may be used effectively to clone genes encoding exported proteins
      with promoters and signal peptide sequences.

PMID- 14682243
TI  - Labeling of three different mouse ES cell lines with the green fluorescent
      protein.
AB  - The linearized plasmid pEGFP-N3 was electroporated into three different mouse ES
      cell lines MESPU-13, MESPU-35 and MESPU-62 derived from 129/ter, C57BL/6J and
      BALB/c mouse strains respectively. Resistant clones were selected in the presence
      of G418 and then were identified under the fluorescence microscope through blue
      exciting light. Positive green clones were primarily expanded and further sorted
      using FACS(fluorescence activated cell sorter). Finally five EGFP stable
      integrated cell strains were obtained and were expanded (2 strains from 129/ter,
      1 strain from C57BL/6J and 2 strains from BALB/c). Each of the five cell strains
      presents high proliferation growth rate and typical morphology characters of ES
      cells and their colonies. More than 85% cells of each cell strain contain normal
      diploid karyotype. Then some analysis such as the AP (alkaline phosphatase)
      staining, oct4 gene expression assay, embryonic body formation and differentiated
      test in vivo and in vitro were made. The results indicated that the stable
      labeled ES cell strains had the normal karyotypes and maintained the ES cell
      typical characteristics.

PMID- 14682244
TI  - Effects of marker-assisted selection under different initial frequency of QTL
      favorable allele.
AB  - A ten-generation continuous selection experiment on a single trait in a closed
      population was carried out by stochastic simulation. It assumed that the trait
      was controlled by polygenes and a single autosomal bi-allelic marked quantitative
      trait locus (QTL). Individual breeding values were estimated through animal model
      marker-assisted best linear unbiased prediction (MB-LUP), and breeding animals
      were selected according to their breeding values. The effects of three levels
      initial frequencies of QTL favorable allele on marker-assisted selection (MAS)
      were studied. The results showed that it would gain higher genetic response when
      implementing MAS on those traits with lower initial frequency of QTL favorable
      allele. When the initial frequency of QTL favorable allele was low, although the
      generation number required for fixing QTL favorable allele in the population
      would be lengthened, its frequency would be increased faster. However, the
      initial frequency of QTL favorable allele had little effects on the inbreeding
      rates.

PMID- 14682245
TI  - [Studies of BMPR-IB and BMP15 as candidate genes for fecundity in little tailed
      han sheep].
AB  - BMPR-IB gene which controls the fecundity of Booroola Merino and BMP15 gene which
      affects the ovulation of Invedale and Hanna were studied as candidate genes on
      the fecundity of Little Tailed Han Sheep, and their mutations and genetic effects
      were analyzed. The results showed that there was a same mutation in BMPR-IB gene
      (A746G) of Little Tailed Han Sheep as that of Booroola Merino. The BB mutation
      genotype was superior in prolific Little Tailed Han Sheep, and the ewes with
      genotype BB had 0.97(P < 0.05) and 1.5(P < 0.01) lambs more than those with
      genotype + + in the first parity and later parities, respectively. It could be
      inferred that BMPR-IB gene was related with the major gene that controls the high
      prolificacy of Little Tailed Han Sheep. While there was not mutation of V31D or
      Q23Ter in BMP15 gene of Little Tailed Han Sheep, it showed that the fecundity
      mechanism of Little Tailed Han Sheep was different from that of Romney sheep.
      Then it was ruled out the possibility that the ovulation of Little Tailed Han
      Sheep was affected by the mutation of BMP15 gene.

PMID- 14682246
TI  - [Polymorphisms of exon 2 of MHC-DRB3 gene in Mongolian and Kazakh Sheep].
AB  - MHC(major histocompatibility complex) is a chromosomal region consisting of a
      group of closely linked loci which are highly polymorphic, which plays a central
      role in the immune system of animals and is almost found in all vertebrates. Its
      expressional product is MHC antigen of which main function is antigen
      presentation. In this study, the exon 2 of MHC-DRB3 gene was amplified by PCR and
      a uniform fragment of 285 bp was obtained in Mongolian Sheep and Kazakh Sheep.
      The 285 bp PCR product was digested with restriction endomuclease HaeIII and
      genetic polymorphism was investigated by PCR-RFLP. Seven alleles were found:
      A(168 bp/117 bp), B(154 bp/117 bp/14 bp), C(154 bp/65 bp/52 bp/14 bp), D(168
      bp/65 bp/52 bp), E(154 bp/131 bp), F(154 bp/66 bp/65 bp), H(220 bp/65 bp). There
      are seventeen genotypes in the tested populations, BB(154 bp/117 bp/14 bp),
      CC(154 bp/65 bp/52 bp/14 bp), EE(154 bp/131 bp), HH(220 bp/65 bp), FF(154 bp/66
      bp/65 bp), AB(168 bp/154 bp/117 bp/14 bp), AC(168 bp/154 bp/117 bp/65 bp/52 bp/14
      bp), AE(168 bp/154 bp/131 bp/117 bp), AH(220 bp/168 bp/117 bp/65 bp), BC(154
      bp/117 bp/65 bp/52 bp/14 bp), CE(154 bp/131 bp/65 bp/52 bp/14 bp), CD(168 bp/154
      bp/65 bp/52 bp/14 bp), CF(154 bp/66 bp/65 bp/52 bp/14 bp), CH(220 bp/154 bp/65
      bp/52 bp/14 bp), DE(168 bp/154 bp/131 bp/65 bp/52 bp), EH(220 bp/154 bp/131 bp/65
      bp), FH(220 bp/154 bp/66 bp/65 bp). By analyzing restriction map, polymorphic
      sites were detected at base position 154, 168 and 220. Statistical results
      indicated that there are significant differences of some genotypic frequencies
      and allelic frequencies between Mongolian Sheep and Kazakh Sheep(P < 0.10, P <
      0.05 or P < 0.01). CC, FF, BC and B, C, F are favorable genotypes and favorable
      alleles respectively in Mongolian Sheep and Kazakh Sheep, In addition, HaeIII CE
      and HaeIII E is favorable genotype and favorable allele respectively in Kazakh
      Sheep. The results of chi 2 test showed that genotypes of MHC-DRB, gene in
      Mongolian Sheep and Kazakh Sheep did not fit with Hardy-Weinberg equilibrium(P <
      0.01).

PMID- 14682247
TI  - [Molecular phylogeny of some species of the acridoidea based on 16S rDNA].
AB  - Based on the 16S rDNA of 8 species (belonging to 8 families of Acridoidea) from
      China and keyed to 8 relative species of Orthoptera from GenBank, the homologus
      sequences were compared. The used frequency of nucleotide was calculated and the
      molecular phylogenetic tree constructed by MEGA microsoft. In the 480 bp fragment
      of mitochondial 16S rDNA, A + T was about 70.7% and G + C only 29.3%. The
      sequence data revealed considerable variation in 188 nucleotide sites among the
      analyzed individuals from 8 different families. The variation rate of
      transversion was larger than or approach to transition. The results showed that
      the ranges of the 16S rDNA nucleotide divergence within species, among species of
      a genus, among genera of a family, and among the same family and suborder were
      1.5%, 3.5%-3.6%, 4.8%-15.8% and 15.2%-25.6%, respectively. The members of the
      same genus and family were grouped together. The phylogenetic relationships of 8
      families were Pyrgomorphidae-->Chrotogonidae-->Pamphagidae-->Oedipodidae-
      >Acrididae--> Arcypteridae-->Gomphoceridae-->Catantopidae. Pyrgomorphidae had
      closer relationships with Chrotogonidae as well as being the most ancestral
      group. Arcypteridae and Gomphoceridae were the sister groups and had closer
      relationships with most evolutionary Catantopidae. Tridactylidae was divided
      firstly as a suborder, which differs from the recent taxonomy distinctly.
      Haglidae (Tettigonoidea) and Gryllidae were grouped into suborder Ensifera,
      Tetrigidae and 8 families of Acridoidea were grouped into suborder Caelifera, as
      same as recent taxonomy.

PMID- 14682248
TI  - [Gene prediction and function research of SARS-CoV(BJ01)].
AB  - Through reading the articles, this study points out the shortage of gene
      prediction and function research about SARS-CoV, and predict it again for
      developing effective drugs and future vaccines. Using twelve gene prediction
      methods to predict coronavirus known genes, we select four better methods
      including Heuristic models, Gene Identification, ZCURVE_CoV and ORF FINDER to
      predict SARS-CoV(BJ01), and use ATGpr for analyzing probability of initiation
      codon and Kozak rule, search transcription regulating sequence(TRS) in order to
      improve the accuracy of predicted genes. Twenty-one probable new genes with more
      than 50 amino acids have been obtained excluding 13 ORFs which are similar to the
      genes of NCBI and relative articles. For predicted proteins, we use ProtParam to
      analyse physical and chemical features; SignalP to analyse signal peptide; BLAST,
      FASTA to search similar sequences; TMPred, TMHMM, PFAM and HMMTOP to analyse
      domain and motif in order to improve reliability of gene function prediction. At
      the same time, we separate the 21 ORFs into four classes using codition of four
      gene prediction methods, match score, match expection and match length between
      predicted gene and Coronavirus known gene. In the end, we discuss the results and
      analyse the reasons.

PMID- 14682249
TI  - [Sequence variation of D12S391 and D11S554 loci in Guangzhou han population].
AB  - To study the core sequence of the hypervariable short tandom repeats, we
      sequenced the alleles of D12S391 and D11S554 loci which show high mutation rate
      in Guangzhou Han population. The D12S391 locus has the basic sequence structure
      (AGAT)8-17 (AGAC)6-10 (AGAT)0-1. The smaller alleles (15-18) at D12S391 locus
      have variation limited to the number of the first repeat (AGAT), whereas the
      larger alleles (19-27) have more complex variation in the number not only of the
      first repeat but also of the other two repeats (AGAC) and (AGAT). Four new
      alleles named 22", 23", 24"' and 27 respectively were found. The D11S554 locus
      has more complex core sequence classified into five sequence types. Three of them
      have the same basic sequence structure (AAAGG) (AAAG)4 (AAAGG)2-3 (AAAG)13-19. In
      the larger alleles (219-249), there are four and five nucleotide repeats. Some of
      the larger alleles(219-249) have one base variation, bases insert or deletion.
      The two loci all have sequence heterogeneity. Our results indicated that the two
      loci D12S391 and D11S554 belong to complex repeats and this adds difficulty to
      their correctly typing. It is essential to construct allelic ladder in each
      population.

PMID- 14682250
TI  - [Variation of insulin receptor substrate-2 gene 3'-untranslated region in
      patients with type 2 diabetes mellitus].
AB  - Insulin receptor substrate-2(IRS-2) belongs to a family of cytoplasmic adaptor
      proteins, which link insulin, insulin-like growth factor-1(IGF-1), and cytokine
      receptor tyrosine kinases to signaling pathways regulating metabolism, growth,
      differentiation, reproduction, and homestasis. Deficiency of IRS-2 in mice causes
      type 2 diabetes mellitus (T2DM), suggesting that abnormal structure and
      dysfunction of the IRS-2 gene may contribute to the pathogenesis of T2DM.
      Variations in the open reading frame (ORF) and promoter region of IRS-2 gene in
      patients with T2DM have been reported over the past few years. These genetic
      variations are from ethnically different patients, confounding any analysis of
      the contribution of IRS-2 gene variations to the development of T2DM. The 3'
      untranslated region(3'-UTR) of IRS-2 gene variation may be contribute to the
      T2DM. So far, the relationship between 3'-UTR of IRS-2 gene variations and T2DM
      have not been investigated. Based on the 3'-UTR of eukaryotic gene plays an
      important role in the eukaryotic gene regulation, we investigated abnormalities
      of IRS-2 gene 3'-UTR and their relation with T2DM in the Chinese population.
      Genomic DNA was extracted from leukocyte of 128 patients with T2DM and 125
      control subjects in Hunan, China. A segment of IRS-2 gene 3'-UTR was scanned by
      polymerase chain reaction (PCR)-denaturing high-performance liquid chromatography
      (DHPLC). All PCR products with abnormal DHPLC pattern were submitted to DNA
      sequence analysis. A T-->C mutation at 4064 bp of IRS-2 gene 3'-UTR was found in
      18 patients with T2DM, while it was only found in 5 control subjects. The
      incidence of the mutation in patients with T2DM were much higher than that in
      contol subjects (14.1% vs 4.0%, x2 = 7.748, P = 0.005). These results indicate
      that the T4064-->C in IRS-2 gene 3'-UTR may be related to Chinese patients with
      T2DM.

PMID- 14682251
TI  - [The structure and regulation of plant proteinase inhibitor genes and their
      strategy in pest control].
AB  - The diverse plant proteinase inhibitors (PIs) genes from different plant species
      have been isolated and their products with one or more genes are targeted at
      different biochemical and physiological process with the insect, and well played
      a potent defensive role against insects and pathogens. The use of recombinant PIs
      and synergistic activation to protect plants has been incorporated in integrated
      pest management program. Though they may not replace the use of chemical
      pesticides in the near future, but effectively complement it. Currently, the role
      and mechanism of action for most of these inhibitors are being studied in detail.
      This article describes the structure of PIs genes, their regulation and
      expression, and discusses the strategy to develop transgenic plants against
      phytophagous insects.

PMID- 14682252
TI  - Point of care can be anywhere.

PMID- 14682253
TI  - Cutting I.T. down to size.

PMID- 14682254
TI  - A tablet a day keeps the errors away.

PMID- 14682255
TI  - Point of care on a roll.

PMID- 14682256
TI  - Docs get PDAs--stat.

PMID- 14682257
TI  - Readers' perspectives. Claims management software vendor and claims
      clearinghouse.

PMID- 14682259
TI  - [Hypothesis: adaptive role of enzymes in the blood].

PMID- 14682258
TI  - [Highly stable regulatory oligopeptides: experience and applications].
AB  - The most stable regulatory peptides (RP) including the new family of RP
      (glyprolines) and derivatives of hybrid peptide MEHFPGP are characterized. High
      ability of glyprolines to penetrate into the blood-stream through the
      gastrointestinal tract is demonstrated. Antiulcer, antithrombotic and
      antidiabetic activities of glyprolines were discovered in experiments on white
      rats. The activity of oligopeptides PGP, PG and GP is compared. Mechanisms of
      glycoprolines activities and feasibility of their administration with connective
      tissue food proteins are discussed. Thus, glyprolines are perspective drugs for
      treatment of gastric ulcer, correction of hemostasis and thrombosis suppression
      prepared for preclinical trial.

PMID- 14682260
TI  - [Regulation of cardiac functions by the L-arginine--nitric oxide system].
AB  - It is shown that intracoronary infusion of L-arginine and sodium nitroprusside
      induces an increase in coronary flow (CF), myocardial contractility (MC) and
      heart rate (HR) in the isolated perfused heart of the rat. Three combinations of
      these effects have been observed in different experiments: generalized effect
      (increase of CF + MC + HR), a double effect in three variants (increase of CF +
      MC, CF + HR, MC + HR) and isolated effect (increase of CF or MC or HR). The data
      obtained suggest that an increase of CF is the main change induced by L-arginine
      in the isolated perfused heart, an increase of MC being secondary in relation to
      a CF increase, i.e. an increase of CF mediates an increase of MC (Gregg's
      phenomenon). A positive inotropic effect of sodium nitroprusside is the result
      mainly of its direct action on the myocardium and to a lesser extent due to a CF
      increase.

PMID- 14682261
TI  - [Formation of nitric oxide by peripheral blood leukocytes in the norm and in
      pathology].
AB  - The study was made of nitric oxide (NO) generation by leukocytes of peripheral
      blood from healthy subjects and patients with a compound trauma. How to isolate
      leukocytes from the whole blood is shown. Leukocyte isolation rate reached 98%.
      Generation of NO by leukocytes was made in the medium containing medium RPMI 1640
      (free of phenol red), calf embryonic serum (5%), L-glutamine (2 mM), gentamycin
      (80 mcg/ml), penicillin (100 U/ml), streptomycin (100 mcg/ml). Incubation lasted
      for 15 h at 37 degrees in tissue culture plates with 24 cells 16 mm in diameter
      (Costor, USA). NO generation was defined in supernatants of cultivated leukocytes
      (5 x 10(6)) with Griss reagent in reaction with stable metabolite nitrite. NO
      content among the leukocytes from healthy subjects was 0.63 +/- 0.08 nmol, in
      trauma 1.10 +/- 0.08 nmol, relative production of NO by healthy subjects was 1.27
      +/- 0.17 mumol/l, in trauma 2/21 +/- 0.18 mumol/l, absolute production was 0.99
      +/- 0.15 mumol/l and 1.98 +/- 0.19 mumol/l, respectively. The findings point to
      an important role of nitric oxide generation by leukocytes in reaction with
      superoxide radical in production of peroxynitrite responsible for severity of
      endotoxicity.

PMID- 14682262
TI  - [Quantitative assessment of eosinophil cationic protein in blood of patients with
      bronchial asthma to study individual variants of inflammation pathogenesis and as
      a monitoring parameter of specific immunotherapy effects in the early periods].

PMID- 14682264
TI  - [Asymmetry of power in the EEG rhythms as a parameter of the brain function].
AB  - Comparison of power asymmetry (PA) has shown that low PA values occurred in the
      posterior cortical parts in adult examinees free of focal brain pathology, in
      anterior and posterior cortical parts in children and in patients with affected
      left hemisphere. In view of immaturity of the brain and unbalanced subcortical
      cortical relationships in children there was enhanced functional activity of
      diencephalo-truncal structures. It is suggested that in patients with damaged
      left hemisphere functional activity of the right hemisphere dominates, therefore
      dominates functional activity of synchronizing diencephalo-truncal structures.
      High interhemispheric asymmetry was detected in anterior parts of the cortex in
      patients free of focal brain pathology as well as in anterior and posterior parts
      of the neocortex in patients with damaged right hemisphere. This can be explained
      by prevalence of activating stem structures in brain functioning. Damage to the
      right hemisphere affects more synchronizing truncal structures and intact left
      hemisphere becomes leading in CNS activity. This hemisphere has primarily
      functional relations with activating stem structures. Thus, the value of
      interhemispheric asymmetry of EEG biopotentials' powers may characterize brain
      function forming in participation of nonspecific stem system regulating
      functional condition of the brain.

PMID- 14682263
TI  - [Effect of perftoran on microcirculation and target organs in early
      atherogenesis].
AB  - Effects of perfluoran, a plasma substitute with a gas-transport function, were
      studied at the stage of dyslipidogenic microangiopathy in rabbits. Changes in
      microcirculation, hemorheology, morphology of the liver, phospholipid composition
      of hepatocytic membranes were examined histologically, histochemically, electron
      microscopically and biochemically. Perfluoran produced a positive effect on
      microcirculation, phospholipid composition of hepatocytic membranes. Individual
      features of these parameters' dynamics were determined for animals.

PMID- 14682265
TI  - [Dramatic character and triumph of ideas proposed ahead of time (to 115th
      anniversary of the birthday of A. D. Speranskii)].

PMID- 14682266
TI  - [Ideas of S. S. Khalatov about pathophysiology as an independent scientific field
      and subject for teaching].

PMID- 14682267
TI  - HIV drugs approved as of August 2003.
AB  - Here is a list of the 19 antiretrovirals currently approved in the U.S., listed
      alphabetically by generic name within each of the four drug classes. Brand names
      and other common names are also included.

PMID- 14682269
TI  - Nelson Mandela on treatment access.
AB  - "If we discard the people who are dying from AIDS, then we can no longer call
      ourselves decent people".

PMID- 14682268
TI  - Major HIV treatment conference in Paris--finding reports online.
AB  - Several Web sites have excellent coverage of the 2nd IAS (International AIDS
      Society) Conference on HIV Pathogenesis and Treatment, July 13-16 in Paris.
      Usually readers can look through a list of titles and click to read the reports
      important to them. We also comment on how software advances could greatly improve
      medical conferences over the next several years.

PMID- 14682270
TI  - Hip protectors to reduce hip fractures.

PMID- 14682271
TI  - Meeting notes from the 43rd Interscience Conference on Antimicrobial Agents and
      Chemotherapy (ICAAC). Abacavir as initial therapy and as a once-daily drug.

PMID- 14682272
TI  - Meeting notes from the 43rd Interscience Conference on Antimicrobial Agents and
      Chemotherapy (ICAAC). Suboptimal response to once-daily abacavir + 3TC +
      tenofovir.

PMID- 14682273
TI  - Meeting notes from the 43rd Interscience Conference on Antimicrobial Agents and
      Chemotherapy (ICAAC). New CCR5 antagonist shows antiretroviral effect.

PMID- 14682274
TI  - Meeting notes from the 43rd Interscience Conference on Antimicrobial Agents and
      Chemotherapy (ICAAC). Prognosis after triple-class failure.

PMID- 14682275
TI  - Meeting notes from the 43rd Interscience Conference on Antimicrobial Agents and
      Chemotherapy (ICAAC). T-1249 for T-20 salvage.

PMID- 14682277
TI  - Meeting notes from the 43rd Interscience Conference on Antimicrobial Agents and
      Chemotherapy (ICAAC). New NNRTI resistance mutations.

PMID- 14682276
TI  - Meeting notes from the 43rd Interscience Conference on Antimicrobial Agents and
      Chemotherapy (ICAAC). Single agent therapy for HIV infection?

PMID- 14682278
TI  - Meeting notes from the 43rd Interscience Conference on Antimicrobial Agents and
      Chemotherapy (ICAAC). Didanosine intensification in NRTI-experienced patients.

PMID- 14682279
TI  - The outs and ins of transposition: from mu to kangaroo.

PMID- 14682280
TI  - [Influence of progression and localization of larynx cancer on speech replacement
      in patients after laryngectomy].

PMID- 14682282
TI  - Rethinking diabetes prevention and control in racial and ethnic communities.
AB  - The growing and disproportionate burden of type 2 diabetes experienced by racial
      and ethnic minority groups in the United States demands a refocusing of public
      health research and interventions if health outcomes are to improve. Public
      health research and practice must address the social production of diabetes,
      broaden the boundaries of how diabetes risk and causation are understood and
      articulated, and establish community health models that reflect the changing
      complexion and sociopolitical dynamics of contemporary urban communities. Relying
      on the traditional one-on-one clinical relationship that has characterized
      diabetes care in the past will not eliminate the diabetes epidemic in racial and
      ethnic communities.

PMID- 14682281
TI  - [Correlation between chronic obstructive bronchial disease and colonic
      anastomosis dehiscence in the elderly].
AB  - BACKGROUND: Anastomotic leakage remains a major complication after large bowel
      surgery. Chronic obstructive pulmonary disease is frequent disease in the
      elderly. AIMS: The authors want to analyze the correlation between systemic
      tissue hypoxia, resulting from chronic obstructive pulmonary disease and
      anastomotic leakage in large bowel surgery in a group of patients over 65 years.
      PATIENTS AND METHODS: In the period 1979-2001 at our surgical Department, 590
      patients underwent colorectal surgery; 211 elderly patients (> 65 years) with
      large bowel anastomosis were selected. In 29/211 (13.7%) chronic obstructive
      pulmonary disease was diagnosed. The group of patients affected by chronic
      obstructive pulmonary disease was defined as group A; the other, as group B. The
      incidence of anastomotic leakage in patients with and without chronic obstructive
      pulmonary disease was evaluated. RESULTS: The overall incidence of anastomotic
      leakage was 5.6% (12/211); a difference in the incidence of anastomotic leakage
      was found in the group A vs. B: 7/29 (24.1 %) in the group A were affected by
      dehiscence vs. 5/182 (2.7%) of group B. This difference was statistically
      significant (p = 0.001). CONCLUSIONS: Chronic obstructive pulmonary disease can
      be a factor increasing the risk of anastomotic leakage. The elderly patient is
      often affected by chronic obstructive pulmonary disease and consequently show an
      higher risk of colonic anastomotic failure than younger patients.

PMID- 14682283
TI  - [Study of Salvia przewalskii and evaluation of its uses].

PMID- 14682284
TI  - National Hormone and Peptide Program, NIDDK: peptide hormones, subunits, antisera
      and other reagents available.

PMID- 14682285
TI  - Bibliography. Current World Literature. Neurology.

PMID- 14682286
TI  - Bibliography. Current World Literature. Allergy, immunology, and related
      disorders.

PMID- 14682287
TI  - Bibliography. Current World Literature. Genetics.

PMID- 14682288
TI  - [Effect of lisinopril on cardiac remodeling in patients with cardiosclerosis
      after myocardial infarction and signs of chronic heart failure].

PMID- 14682295
TI  - Court upholds murder verdict on doctor who ended woman's life.

PMID- 14682296
TI  - Readers want transparency in link between doctors and drug firms.

PMID- 14682297
TI  - [Effect of imidazoline receptor agonist moxonidine on the state of
      microcirculation and renal function in patients with hypertension and diabetes
      mellitus type 2].

PMID- 14682298
TI  - Reflections on the human embryonic stem cell debate.

PMID- 14682299
TI  - [Hemodynamics and right ventricular diastolic function in adolescents with
      various degree of scoliosis].

PMID- 14682300
TI  - [The treatment of arterial hypertension: new trials--new approaches].

PMID- 14682301
TI  - [Intravenous nitroglycerin in cardiology].

PMID- 14682302
TI  - Intravenous busulfan in pretransplant chemotherapy: bioavailability and patient
      benefit.

PMID- 14682303
TI  - Colonic explosion complicating colonoscopic electrotherapy.

PMID- 14682304
TI  - Validity of using standard error of mean in trials.

PMID- 14682305
TI  - Prophylactic clip application.

PMID- 14682306
TI  - Choose to be part of the solution--not part of the problem.

PMID- 14682307
TI  - Honoring the honoree.

PMID- 14682308
TI  - Double the dedication. Interview by Tammi Brunello.

PMID- 14682309
TI  - Neurological devices; classification of human dura mater. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying human dura mater intended
      to repair defects in human dura mater into class II (special controls). This
      action is being taken to establish sufficient regulatory control to provide
      reasonable assurance of the safety and effectiveness of the device. Elsewhere in
      this issue of the Federal Register, FDA is announcing the availability of a
      guidance document entitled "Class II Special Controls Guidance Document: Human
      Dura Mater" that will serve as the special control for this device.

PMID- 14682311
TI  - Brave new IVF.

PMID- 14682310
TI  - NMR studies of oxyleghemoglobin: assignment of distal histidine proton resonances
      and evidence for pH-dependent changes in conformation.
AB  - The resonance of the C-2 proton of the distal histidine has been assigned in the
      400 MHz 1H-NMR spectrum of soybean ozyleghemoglobin a. This resonance is subject
      to a very large ring current shift from the heme and occurs to high field of the
      residual HO2H peak. The pH dependence was measured from a series of nuclear
      Overhauser effect difference spectra over a range of pH values. The resonance
      moves to high field with decreasing pH and reflects titration of a one proton
      dissociable group with pK 5.5. Resonances of the heme substituents and distal
      amino acid side-chains are also sensitive to this titration. Changes in ring
      current shifts and nuclear Overhauser effects indicate that a conformational
      change occurs in the heme pocket upon titration of the pK 5.5 group. We propose
      that protonation of the distal histidine with pK 5.5 is accompanied by movement
      of the imidazole ring towards the heme normal. This movement would allow
      interaction between the ligated oxygen molecule and the protonated distal
      histidine at acid pH.

PMID- 14682312
TI  - The next IVF revolution?

PMID- 14682313
TI  - A healthy investment?

PMID- 14682314
TI  - Stunting growth harms fertility.

PMID- 14682315
TI  - Just following orders?

PMID- 14682316
TI  - Bioethics and anthropology: bridges and barriers to transdisciplinary research.

PMID- 14682317
TI  - The absolute ethical requirement of individual, informed consent: a commentary on
      Barrett and Parker.

PMID- 14682318
TI  - Amyotrophic lateral sclerosis in Olmsted County, Minnesota, 1925 to 1998.

PMID- 14682319
TI  - Culture, community and consent: a response to Barrett and Parker.

PMID- 14682321
TI  - Age discrimination in trials and treatment: old dogs and new tricks.
AB  - It is common for drug trials to exclude older people, usually over 65 or 70. Many
      of the drugs which are successfully tested are then registered and become
      available either on prescription or over the counter. Healthcare professionals
      are left in a bind: either they do not prescribe the medications to those in the
      excluded age groups because of the lack of age-relevant data, or they prescribe,
      off-label, despite the lack of systematic collection of age-relevant data.
      Alternatively, if the pharmaceutical is available without prescription, older
      people may be buying without any inkling or warning that the drug was never tried
      on people of their own age. Either way, our older fellow citizens are not getting
      the same ethical treatment as younger adults. Compounding the questionable ethics
      involved is the fact that as age increases, the ratio of women to men increases.
      Amplified by the fact that women consume more pharmaceuticals than do men, the
      discrimination takes on a distinctively sexist slant as well as an ageist one.
      Two other groups often excluded from trials are (a) minors and (b) pregnant or
      lactating women. But the rationale for their exclusion is different from that for
      the exclusion of seniors. A major reason for these two groups' exclusion is the
      legal incapacity of the young to consent and the concomitant flow-on liability
      for injuries and damages to the youngsters. The potential exposure to later legal
      claims may be a strong motivating force for pharmaceutical companies to exclude
      from their trials people without legal capacity to consent. But the third group
      of people, seniors, is excluded by reference to their seniority not their
      inability to give informed consent. While the other two exclusions can be
      explained in terms of moral, social and legal conventions, seniority alone is
      based on two practical concerns: firstly, whether seniors are likely to die
      before the end of the trial, and secondly, the compounding effects of the so
      called diseases of old age. Together, these concerns are thought to justify
      seniority exclusion in the interests of clean science. This paper examines some
      of the ethical issues, the implicit ageism and sexism in the exclusion of
      seniors. The discussion considers the ethical consequences of the exclusion,
      where seniors are either taking drugs in the absence of evidence-based trials on
      their age groups, or are denied drugs because they are untried on the age groups.

PMID- 14682320
TI  - Ethics of research involving humans: uniform processes for disparate categories?
AB  - The Australian Health Ethics Committee's National Statement on Ethical Conduct in
      Research Involving Humans (1999) expanded the health and medical focus of
      preceding statements by including all disciplines of research. The Statement
      purports to promote a uniformly high ethical standard for this expanded range of
      research, and is endorsed by, inter alia, the Australian Academy of the
      Humanities, the Australian Academy of Science, and the Academy of Social Sciences
      in Australia. High ethical standards should apply to all research involving
      humans. However, uniformity in the review processes of disparate research
      endeavors is not a necessary condition for uniformly high ethical standards.
      Bringing the ethical review of all research under a model which has developed
      within the context of health and medical research ethics for over thirty years
      may be inappropriate and at times incoherent. The language, methods, nature and
      products of research in areas such as the Humanities are often very different
      from those of health, medical and other sciences. The Behavioral and Social
      Sciences Ethics Review Committee at The University of Queensland (UQ) had, since
      the mid-1980s, considered that the guidelines of the time did, in fact, cover all
      aspects of human experimentation. We describe the ways in which this position was
      implemented, how issues raised by the new wording in the National Statement have
      been recently managed by UQ's research ethics committees, and point to
      outstanding questions.

PMID- 14682322
TI  - Violence in adolescence: a puzzle that demands holistic understanding and
      interdisciplinary collaboration.

PMID- 14682323
TI  - Are the courts excessively deferential to the medical profession?

PMID- 14682324
TI  - The right to refuse medical treatment under the European Convention on Human
      Rights.

PMID- 14682325
TI  - The principle of double effect and terminal sedation.

PMID- 14682326
TI  - Morphine vs. ABT-594: a reexamination by the principle of double effect.

PMID- 14682327
TI  - Paternalism and access to medical records.

PMID- 14682328
TI  - Toward justice in the organ trade.

PMID- 14682329
TI  - Organ transplants from living donors.

PMID- 14682330
TI  - Kidney donations from the legally incompetent in Jewish and comparative law.

PMID- 14682331
TI  - Artificial techniques of procreation: legal and moral aspects.

PMID- 14682332
TI  - Organs as assets.

PMID- 14682333
TI  - Ownership of organs taken from a living person.

PMID- 14682334
TI  - "Ownership" "assets" and transferability of "property rights".

PMID- 14682335
TI  - Gift of organs--a note.

PMID- 14682336
TI  - Assisted-suicide activism: patience and plastic bags.

PMID- 14682337
TI  - Research misconduct events increased yet again in 2002.

PMID- 14682338
TI  - Sailing SCHIP through troubled waters.
AB  - As the State Children's Health Insurance Program (SCHIP) enters its sixth year of
      operation, states have continued their commitment to children's coverage and to
      reaching out to the uninsured. This issue brief explores the current status of
      SCHIP in light of fiscal pressures that have been created by the state budget
      crisis. It highlights some of the key successes in the program thus far and notes
      several examples of state initiatives to serve particularly vulnerable
      populations and collect outcomes data and information about access to care.

PMID- 14682339
TI  - At home with Down syndrome and gender.
AB  - I argue that there is an important analogy between sex selection and selective
      abortion of fetuses diagnosed with Down syndrome. There are surprising parallels
      between the social construction of Down syndrome as a disability and the deeply
      entrenched institutionalization of sexual difference in many societies.
      Prevailing concepts of gender and mental retardation exert a powerful influence
      in constructing the sexual identities and life plans of people with Down
      syndrome, and also affect their families' lives.

PMID- 14682340
TI  - Bring back the acetyls - a novel anticancer movement.

PMID- 14682341
TI  - Nanoshell destruction of inoperable tumours.

PMID- 14682342
TI  - Genetic counseling and the disabled: feminism examines the stance of those who
      stand at the gate.
AB  - This essay examines the possible systematic bias against the disabled in the
      structure and practice of genetic counseling. Finding that the profession's
      "nondirective" imperative remains problematic, the authors recommend that
      methodology developed by feminist standpoint epistemology be used to incorporate
      the perspective of disabled individuals in genetic counselors' education and
      practice, thereby reforming society's view of the disabled and preventing
      possible negative effects of genetic counseling on the self-concept and material
      circumstance of disabled individuals.

PMID- 14682343
TI  - Tamoxifen-resistant cells sensitive to oestradiol.

PMID- 14682344
TI  - Vaccine hope for acute promyelocytic leukaemia.

PMID- 14682345
TI  - Love's labor in the health care system: working toward gender equity.
AB  - In this commentary on Eva Feder Kittay's Love's Labor: Essays on Women, Equality,
      and Dependency, I focus on Kittay's dependency theory. I apply this theory to an
      analysis of women's inadequate access to high-quality, cost-effective healthcare.
      I conclude that while quandaries remain unresolved, including getting men to do
      their share of dependency work, Kittay's book is an important and original
      contribution to feminist healthcare ethics and the development of a normative
      feminist ethic of care.

PMID- 14682346
TI  - Phase I melanoma trial puts Chile on the map.

PMID- 14682347
TI  - Vital gene linked to parathyroid carcinoma.

PMID- 14682348
TI  - Australia approves thalidomide.

PMID- 14682349
TI  - Cone-snail depletion threatens medical research.

PMID- 14682350
TI  - Formaldehyde link to cancer.

PMID- 14682351
TI  - Are life patents ethical? Conflict between Catholic social teaching and
      agricultural biotechnology's patent regime.
AB  - Patents for genetic material in the industrialized North have expanded
      significantly over the past twenty years, playing a crucial role in the current
      configuration of the agricultural biotechnology industries, and raising
      significant ethical issues. Patents have been claimed for genes, gene sequences,
      engineered crop species, and the technical processes to engineer them. Most
      critics have addressed the human and ecosystem health implications of genetically
      engineered crops, but these broad patents raise economic issues as well. The
      Catholic social teaching tradition offers guidelines for critiquing the economic
      implications of this new patent regime. The Catholic principle of the universal
      destination of goods implies that genes, gene sequences, and engineered crop
      varieties are ineligible for patent protection, although the processes to
      engineer these should be eligible. Religious leaders are likely to make a more
      substantive contribution to debates about agricultural biotechnology by
      addressing these life patents than by speculating that genetic engineering is
      "playing God."

PMID- 14682352
TI  - Chemoprevention: eat ginger, rub on pomegranate.

PMID- 14682353
TI  - Indian registry to study hereditary cancers.

PMID- 14682354
TI  - Psychosocial genetic counseling in the post-nondirective era: a point of view.
AB  - For three decades nondirectiveness has served as the central ethos for genetic
      counseling. It has evolved from narrow definitions defining what should not be
      done to broad definitions that promote active counseling skills in support of
      client autonomy and informed decision making. As broad definitions have been
      formulated, the term "nondirective" has become largely irrelevant to their
      content; it persists primarily as a historic relic. It has thus become an
      impediment to creative theory and clinical practice. I propose that
      nondirectiveness be replaced as the central ethos, while relevant components
      (providing balanced information, not imposing the counselor's values) are
      retained as elements of practice and ethics. This raises the question of what
      principle(s) should be adopted as a new guiding ethos. To promote a discussion of
      that issue I propose that the central ethos of genetic counseling should be to
      bring the psychosocial component into every aspect of the work.

PMID- 14682355
TI  - Employer commitment can help overcome obstacles to effective alcohol treatment.

PMID- 14682356
TI  - Nondirectiveness and its lay interpretations: the effect of counseling style,
      ethnicity and culture on attitudes towards genetic counseling among Jewish and
      Bedouin respondents in Israel.
AB  - To evaluate the effects of ethnicity, culture, and counseling style on the
      interpretation of nondirectiveness in genetic counseling, a questionnaire
      containing premarital and prenatal case vignettes in two versions
      (pessimistic/optimistic) was administered to 281 Jewish and 133 Bedouin
      respondents. The first study population was comprised of Jewish students enrolled
      in a university and a community college in the Negev (southern part of Israel).
      The second study population was comprised of Muslim-Bedouin college students from
      the same area. The majority of Jewish respondents interpreted the nondirective
      message as intended by counselors, while the majority of Bedouin respondents did
      not. Counseling style was found to have a statistically significant effect on the
      interpretation of the general role of counseling. Gender and susceptibility were
      not found to have a significant effect on interpretation. Group differences are
      analyzed through a cultural lens in which different interpretive norms can
      generate expectations for either nondirectiveness or directiveness.

PMID- 14682357
TI  - Attitudes of health care trainees about genetics and disability: issues of
      access, health care communication, and decision making.
AB  - Prior studies suggest that knowledge and attitudes of health care professionals
      influence patient communication and medical decision-making. To study this
      dynamic in the context of genetic disability, we developed a survey on health
      professionals' attitudes regarding disability and genetic screening and pilot
      tested it on a sample of medical students, residents, and genetic counseling
      students (N=85). Despite minimal experience with disability or genetics, most
      respondents reported feeling comfortable dealing with genetics (59%) and
      disability (75%). The majority felt that disability caused significant suffering
      for both the person (51%) and family (64%), and that research should be directed
      toward preventing genetic disability (62%). Similar to prior literature,
      perceived "Quality of Life" was most often based on degrees of physical and
      cognitive functioning, pain, and social support. However, differences were found
      between genetic counseling trainees and other medical trainees in their relative
      emphasis of social versus medical issues in questions of disability and genetic
      testing, and these response patterns were associated with differences in the
      groups' priorities for offering information about social resources. Respondents
      agreed that access to genetic testing and information is personal and that
      testing should be available upon request for oneself (68%) and to a lesser degree
      for one's fetus (55%) or child (41%). However, the same individuals frequently
      stated that society should regulate access to such technologies. Although most
      felt that the patient and professional should jointly make such decisions on a
      case-by-case basis, it was also seen as appropriate for the health care
      professional to occasionally decline genetic testing. It seems appropriate that
      training and experience influence knowledge and attitudes. Therefore, it is
      critical to document knowledge and attitudes of various health care providers and
      trainees, including differences between various specialties, to improve
      educational interventions geared to this area.

PMID- 14682358
TI  - Signalling mechanisms mediating neuronal responses to guidance cues.
AB  - Several families of extracellular guidance cues have been implicated in guiding
      neurons and axons to their appropriate destinations in the nervous system. Their
      receptors include single- and seven-transmembrane receptors, and their signal
      transduction pathways converge onto the Rho family of small GTPases, which
      control the cytoskeleton. A single guidance protein can use different mechanisms
      to regulate different kinds of motility or the motilities of different cell
      types. There is crosstalk between the signalling pathways initiated by distinct
      guidance cues. Studies of neuronal guidance mechanisms have shed light not only
      on neural development, but also on other processes that involve the extracellular
      regulation of the cytoskeleton.

PMID- 14682359
TI  - The local differentiation of myelinated axons at nodes of Ranvier.
AB  - Efficient and rapid propagation of action potentials in myelinated axons depends
      on the molecular specialization of the nodes of Ranvier. The nodal region is
      organized into several distinct domains, each of which contains a unique set of
      ion channels, cell-adhesion molecules and cytoplasmic adaptor proteins. Voltage
      gated Na+ channels - which are concentrated at the nodes - are separated from K+
      channels - which are clustered at the juxtaparanodal region - by a specialized
      axoglial contact that is formed between the axon and the myelinating cell at the
      paranodes. This local differentiation of myelinated axons is tightly regulated by
      oligodendrocytes and myelinating Schwann cells, and is achieved through complex
      mechanisms that are used by another specialized cell-cell contact - the synapse.

PMID- 14682360
TI  - Proteinase-activated receptors in the nervous system.
AB  - Recent data point to important roles for proteinases and their cognate proteinase
      activated receptors (PARs) in the ontogeny and pathophysiology of the nervous
      system. PARs are a family of G-protein-coupled receptors that can affect neural
      cell proliferation, morphology and physiology. PARs also have important roles in
      neuroinflammatory and degenerative diseases such as human immunodeficiency virus
      associated dementia, Alzheimer's disease and pain. These receptors might also
      influence the pathogenesis of stroke and multiple sclerosis, conditions in which
      the blood-brain barrier is disrupted. The diversity of effects of PARs on neural
      function and their widespread distribution in the nervous system make them
      attractive therapeutic targets for neurological disorders. Here, we review the
      roles of PARs in the central and peripheral nervous systems during health and
      disease, with a focus on neuroinflammatory and degenerative disorders.

PMID- 14682361
TI  - The molecular basis of water transport in the brain.
AB  - Brain function is inextricably coupled to water homeostasis. The fact that most
      of the volume between neurons is occupied by glial cells, leaving only a narrow
      extracellular space, represents an important challenge, as even small
      extracellular volume changes will affect ion concentrations and therefore
      neuronal excitability. Further, the ionic transmembrane shifts that are required
      to maintain ion homeostasis during neuronal activity must be accompanied by
      water. It follows that the mechanisms for water transport across plasma membranes
      must have a central part in brain physiology. These mechanisms are also likely to
      be of pathophysiological importance in brain oedema, which represents a net
      accumulation of water in brain tissue. Recent studies have shed light on the
      molecular basis for brain water transport and have identified a class of
      specialized water channels in the brain that might be crucial to the
      physiological and pathophysiological handling of water.

PMID- 14682362
TI  - The legacy of Donald O. Hebb: more than the Hebb synapse.
AB  - Neuroscientists associate the name of Donald O. Hebb with the Hebbian synapse and
      the Hebbian learning rule, which underlie connectionist theories and synaptic
      plasticity, but Hebb's work has also influenced developmental psychology,
      neuropsychology, perception and the study of emotions, as well as learning and
      memory. Here, we review the work of Hebb and its lasting influence on
      neuroscience in honour of the 2004 centenary of his birth.

PMID- 14682363
TI  - Tiered-provider networks: patients face cost-choice trade-offs.

PMID- 14682364
TI  - Proceedings of the 17th annual meeting of Japanese Society for Biological
      Sciences in Space.

PMID- 14682365
TI  - Individual researcher liability for clinical research on humans.
AB  - Despite international guidelines and federal regulations, a recent rash of
      problems in clinical trials have highlighted weaknesses in the oversight process.
      The federal regulatory system depends on self-policing by researchers and
      institutions. Because the existing system is overworked, applying common law
      forms of liability to clinical researchers may encourage improvements in this
      self-regulation. While research necessarily involves uncertainties, researchers
      have the greatest direct control over the implementation of the research protocol
      and the most extensive direct contact with subjects, and must bear corresponding
      responsibility for acts which fall below the standard of care. This paper argues
      that the existing FDA patient protections should be adopted as the standards of
      care for researchers. It examines the possible application of negligence,
      negligence per se, and fraud and misrepresentation claims against researchers.

PMID- 14682366
TI  - The high road to success: how investing in ethics enhances corporate objectives.
AB  - There is a growing gap between the tidal wave of information emerging from the
      Human Genome Project and other molecular biology initiatives, and the clinical
      research needed to transform these discoveries into new diagnostics and
      therapeutics. While genomics-based technologies are being rapidly integrated into
      pharmaceutical R&D, many steps in the experimental process are still reliant on
      traditional surrogate model systems whose predictive power about human disease is
      incomplete or inaccurate. There is a growing trend underway in the research
      community to introduce actual human disease understanding as early as possible
      into discovery, thereby improving accuracy of results throughout the R&D
      continuum. Such an approach (known as clinical genomics: the large scale study of
      genes in the context of actual human disease) requires the availability of large
      quantities of ethically and legally sourced, high-quality human tissues with
      associated clinical information.Heretofore, no source could meet all of these
      requirements. Ardais Corporation was the first to address this need by pioneering
      a systematized, standardized network for the collection, processing,
      dissemination and research application of human tissue and associated clinical
      information, all of which rest on the highest ethical standards. Based on a novel
      model of collaboration between industry and the academic/medical community,
      Ardais has created procedures, structures, technologies, and information tools
      that collectively compromise a new paradigm in the application of human disease
      to biomedical research. Ardais now serves as a clinical genomics resource to
      dozens of academic researchers and biopharmaceutical companies, providing
      products and services to accelerate and improve drug discovery and development.

PMID- 14682367
TI  - Bibliography. Current world literature. Pediatric otolaryngology.

PMID- 14682368
TI  - Bibliography. Current world literature. Laryngology and bronchoesophagology.

PMID- 14682369
TI  - Behavioral genetics: scientific and social acceptance.
AB  - Human behavioral genetics can be broadly defined as the attempt to characterize
      and define the genetic or hereditary basis for human behavior. Examination of the
      history of these scientific enterprises reveals episodes of controversy, and an
      apparent distinction between scientific and social acceptance of the genetic
      nature of such complex behaviors. This essay will review the history and
      methodology of behavioral genetics research, including a more detailed look at
      case histories involving behavioral genetic research for aggressive behavior and
      alcoholism. It includes a discussion of the scientific versus social qualities of
      the acceptance of behavioral genetics research, as well as the development of a
      general model for scientific acceptance involving the researchers, the scientific
      literature, the scientific peer group, the mainstream media, and the public at
      large. From this model follows a discussion of the means and complications by
      which behavioral genetics research may be accepted by society, and an analysis of
      how future studies might be conducted.

PMID- 14682370
TI  - Subgroups of working uninsured require different enrollment strategies.
AB  - Today, more than 41 million Americans are uninsured. Perhaps the most perplexing
      aspect of this problem is that many of them are employed. Barriers to obtaining
      employer-sponsored insurance (ESI) are not well understood, but new research has
      shed light on the characteristics of the working uninsured.

PMID- 14682371
TI  - Maintaining informed consent for doctor-patient confidentiality: more serious
      failings in the HHS medical regulations.
AB  - The Health and Human Services (HHS) regulations on medical records, approved by
      the Clinton administration in December 2000, and by the Bush administration in
      April 2001, improved confidentiality protection from the preliminary rule by
      incorporating fair information practices, consent and minimal necessary
      disclosures provisions. The Fall 2002 removal of the consent requirements
      seriously breaches these promises. The consent provisions need to be
      strengthened, not weakened.

PMID- 14682373
TI  - Clinical trials with retrovirus mediated gene therapy--what have we learned?
AB  - Retrovirus (RV) has been one of the earliest recombinant vectors to be
      investigated in the context of cancer gene therapy. Experiments in cell culture
      and in animal brain tumor models have demonstrated the feasibility of RV mediated
      gene transduction and killing of glioma cells by toxicity generating transgenes.
      Phase I and II clinical studies in patients with recurrent malignant glioma have
      shown a favorable safety profile and some efficacy of RV mediated gene therapy.
      On the other hand, a prospective randomized phase III clinical study of RV gene
      therapy in primary malignant glioma failed to demonstrate significant extension
      of the progression-free or overall survival times in RV treated patients. The
      failure of this RV gene therapy study may be due to the low tumor cell
      transduction rate observed in vivo. The biological effects of the treatment may
      also heavily depend on the choice of transgene/prodrug system and on the vector
      delivery methods. Retrovirus clinical trials in malignant glioma have
      nevertheless produced a substantial amount of data and have contributed toward
      the identification of serious shortcomings of the non-replicating virus vector
      gene therapy strategy. Novel types of therapeutic virus vector systems are
      currently being designed and new clinical protocols are being created based on
      the lessons learned from the RV gene therapy trials in patients with malignant
      brain tumors.

PMID- 14682372
TI  - Oncolytic viruses: clinical applications as vectors for the treatment of
      malignant gliomas.
AB  - Gene therapy using viral vectors for the treatment of primary brain tumors has
      proven to be a promising novel treatment modality. Much effort in the past has
      been placed in utilizing replication-defective viruses to this end but they have
      shown many disadvantages. Much recent attention has been focused on the potential
      of replication-competent viruses to discriminatingly target, replicate within,
      and destroy tumor cells via oncolysis, leaving adjacent post-mitotic neurons
      unharmed. The engineered tumor-selective herpes simplex-1 virus (HSV-1) mutants
      G207 and HSV1716 have completed Phase I investigations in the treatment of
      recurrent high-grade glioma. The results of these clinical trials are reviewed
      here. This review also aims to examine the manipulation and development of other
      viruses for the treatment of malignant glioma, including Newcastle disease virus,
      reovirus, poliovirus, vaccinia virus, and adenoviruses, in particular the
      adenovirus mutant ONYX-015.

PMID- 14682374
TI  - Clinical trials of adenoviruses in brain tumors: a review of Ad-p53 and oncolytic
      adenoviruses.
AB  - Adenoviruses have been critical in the development of the molecular approaches to
      brain tumors. They have been engineered to function as vectors for delivering
      therapeutic genes in gene therapy strategies, and as direct cytotoxic agents in
      oncolytic viral therapies. This review outlines the uses of adenoviruses in brain
      tumor therapy by examining clinical trials of adenovirus-mediated p53 gene
      therapy and by reviewing the application of two conditionally replicative
      adenoviruses (CRAds) ONYX-015 and Delta 24 in brain tumors. The potential
      clinical use of CRAds that deliver trangenes, particularly p53, is also
      discussed.

PMID- 14682375
TI  - Cytokine immuno-gene therapy for treatment of brain tumors.
AB  - The prognosis for patients with an intracerebral (i.c.) neoplasm is poor.
      Conventional treatments such as surgery, radiation therapy and chemotherapy have
      done little to affect long-term survival, and new methods of treatment are
      urgently needed. In this report approaches involving cytokine gene therapy in
      treatment of malignant brain tumors are reviewed and contrasted to a strategy
      developed in this laboratory involving the use of allogeneic cells genetically
      modified to secrete cytokines. In our studies, mice with an i.c. glioma, melanoma
      or breast carcinoma treated solely by intratumoral injections with allogeneic
      cells genetically modified to secrete interleukin-2 (IL-2) were found to survive
      significantly longer than mice in various control groups. The anti-tumor response
      was mediated predominantly by T-cell subsets (CD8+ and NK/LAK cells). The
      injections resulted in the killing of only the neoplastic cells; non-neoplastic
      cells were unaffected. Experiments involving treatment of animals with i.c. tumor
      using subcutaneous injections of cytokine-secreting allogeneic cells in the
      presence of tumor antigens demonstrated no effect in prolonging survival in spite
      of the development of a vigorous systemic anti-tumor immune response. Of special
      interest, mice injected intracerebrally with the cytokine-secreting allogeneic
      cells alone exhibited no neurologic defect and there were no adverse effects on
      survival. The injection of cytokine-secreting allogeneic cells into the
      microenvironment of an i.c. tumor is hypothesized to induce an anti-tumor immune
      response capable of prolonging survival. This pre-clinical animal data directly
      translates into clinical treatments for patients with a malignant i.c. tumor.

PMID- 14682376
TI  - Clinical gene therapy for brain tumors. Liposomal delivery of anticancer molecule
      to glioma.
AB  - Liposomes are one of the most promising delivery systems for genes, proteins, and
      other biological molecules and they are expected to become a new therapeutic tool
      for the treatment of brain tumors, especially malignant gliomas. Until now,
      transfer of anticancer molecules using liposomes has been studied by a lot of
      investigators and it has been found to induce regression of experimental gliomas,
      resulting in establishing some original and effective therapies. Gene therapy
      using cationic liposomes is also one of them. Here we introduce the advanced
      medicine for brain tumors using liposomes containing some anticancer molecules
      (for example, gene, antibody, antisense, or magnetite), based on our basic and
      clinical research.

PMID- 14682377
TI  - Treatment of progressive or recurrent glioblastoma multiforme in adults with
      herpes simplex virus thymidine kinase gene vector-producer cells followed by
      intravenous ganciclovir administration: a phase I/II multi-institutional trial.
AB  - To determine the safety and evaluate the efficacy of repeated administration of
      virus-producing cells (GLI 328) containing the herpes simplex virus thymidine
      kinase gene followed by ganciclovir treatment in adults with recurrent
      glioblastoma multiforme, we conducted a phase I/II multi-institutional trial.
      Eligible patients underwent surgical resection of tumor, followed by injections
      of vector producing cells (VPC) into the brain adjacent to the cavity. An Ommaya
      reservoir placed after surgery was used to inject a further dose of VPC seven
      days after surgery, followed seven days later by ganciclovir. Further gene
      therapy was given at 28-day intervals for up to a total of five cycles. Toxicity
      and anti-tumor effect were assessed. Of 30 patients who enrolled in the study, 16
      experienced serious adverse events possibly related to the experimental therapy.
      Laboratory testing, including polymerase chain reaction analysis to detect
      replication-competent retrovirus in peripheral blood lymphocytes and tissues, as
      well as co-cultivation bioassays, were negative. Before receiving ganciclovir,
      37% of the patients showed evidence of transduced peripheral blood leukocytes,
      but only 12% showed a persistence of transduced cells at the end of the first
      cycle of ganciclovir. Median survival was 8.4 months. Twenty percent of the
      patients (n = 6) survived more than 12 months from the date of study entry. This
      treatment modality is feasible and appears to have some evidence of efficacy.
      Toxicity may be related in part to the method of gene delivery.

PMID- 14682378
TI  - Adenovirus/herpes simplex-thymidine kinase/ganciclovir complex: preliminary
      results of a phase I trial in patients with recurrent malignant gliomas.
AB  - The management of patients with glioblastoma remains challenging with an average
      survival of 32-56 weeks. We report on a clinical trial of patients with recurrent
      glioblastoma treated with adenovirus/herpex simplex-thymidine kinase/ganciclovir
      (ADV/HSV-tk/GC). Entry criteria for this study included: recurrent malignant
      glioma after surgical resection and conventional radiation therapy. At the time
      of recurrence, computerized volumetric resection of the tumor was performed and
      the ADV/HSV-tk complex was injected in the tumor bed. GC was administered 24 h
      after surgery (10 mg/kg/day) for 7 days. Patients were divided into 3 ADV/HSV-tk
      dose-escalating cohorts. Adenoviral vector shedding, and local or systemic
      toxicity did not occur in this study. Magnetic resonance imaging showed lack of
      increased brain edema in the treated patients. Histological examination of the 5
      patients that had repeated surgery after gene therapy treatment showed lack of
      tissue toxicity. Additionally, PCR for HSV-tk was negative in the brain 3 months
      after injection. The patients' Karnofsky score was maintained > or = 70 in 8/10
      patients (80%) and 5/9 patients (55%) 3 and 6 months respectively, after gene
      therapy. Ten of 11 patients survived > or = 52 weeks from diagnosis with an
      average survival of 112.3 weeks. One patient is still alive 248 weeks from
      diagnosis. These data show that the ADV/HSV-tk/GC complex at the dose used in
      this study is safe. Additional dose escalation is currently in progress.

PMID- 14682380
TI  - Evolution of a gene therapy clinical trial. From bench to bedside and back.
AB  - Developing and conducting gene therapy clinical trials poses unique challenges
      which must be addressed to satisfy regulatory requirements and, most importantly,
      to protect human subjects. Experimental products used for gene transfer studies,
      such as viral vectors, are often complex and cannot be sterilized or completely
      characterized to the extent of a typical pharmaceutical. Thus, quality and
      characterization must be built into the production process. Extensive preclinical
      studies must be performed to determine the feasibility of the approach, the
      safety of the product, and the appropriate dose range to evaluate in humans. Once
      a clinical trial is initiated, subjects must be followed carefully for short- and
      long-term toxicity especially since preclinical studies may not adequately
      predict the toxicity profile of these novel, complicated products. Results of
      early phase studies in gene therapy have often sent the investigators back to the
      laboratory to improve the delivery vector or identify a more potent or less toxic
      gene. This circular developmental process is expected for the early stages of a
      new technology such as gene therapy. Although these hurdles appear extensive,
      they can be overcome, as evidenced by the initiation of more than 500 clinical
      gene therapy trials in the United States to date, and are imperative for the
      maintenance of high-quality studies and public trust. This article describes the
      step-by-step process for developing a gene therapy trial incorporating specific
      examples relevant to neuro-oncology.

PMID- 14682381
TI  - Greenwood memorial lecture: relaxin' Hawaii.

PMID- 14682379
TI  - Imaging in gene therapy of patients with glioma.
AB  - Over 10 years ago, the first successful gene therapy paradigms for experimental
      brain tumors models have been conducted, and they were thought to revolutionize
      the treatment of patients with gliomas. Application of gene therapy has been
      quickly forced into clinical trials, the first patients being enrolled in 1994,
      with overall results being disappointing. However, single patients seemed to
      benefit from gene therapy showing long-term treatment response, and most of these
      patients bearing small glioblastomas. Whereas the gene therapy itself has been
      performed with high sophistication, limited attention has been paid on
      technologies, which (i) allow an identification of viable target tissue in
      heterogenous glioma tissue and which (ii) enable an assessment of successful
      vector administration and vector-mediated gene expression in vivo. However, these
      measures are a prerequisite for the development of successful gene therapy in the
      clinical application. As biological treatment strategies such as gene and cell
      based therapies hold promise to selectively correct disease pathogenesis,
      successful clinical implementation of these treatment strategies rely on the
      establishment of molecular imaging technology allowing the non-invasive
      assessment of endogenous and exogenous gene expression in vivo. Imaging
      endogenous gene expression will allow the characterization and identification of
      target tissue for gene therapy. Imaging exogenously introduced cells and genes
      will allow the determination of the 'tissue dose' of transduced cell function and
      vector-mediated gene expression, which in turn can be correlated to the induced
      therapeutic effect. Only these combined strategies of non-invasive imaging of
      gene expression in vivo will enable the establishment of safe and efficient
      vector administration and gene therapy protocols for clinical application. Here,
      we review some aspects of imaging in gene therapy trials for glioblastoma, and we
      present a 'proof-of-principle' 2nd-generation gene therapy protocol integrating
      molecular imaging technology for the establishment of efficient gene therapy in
      clinical application.

PMID- 14682382
TI  - Activated eosinophils upregulate the metastasis suppressor molecule E-cadherin on
      prostate tumor cells.
AB  - Cell adhesion molecules (CAMs) play an important role in cancer metastasis by
      facilitating attachment to vascular endothelia, invasion and spread into
      secondary tissue sites. We have shown that activated eosinophils (EosA) inhibited
      the growth of prostate cancer (Pca) cells in vitro. In the present study, we
      examined the ability of EosA 24 hr conditioned supernatants (EosAcs) to modulate
      the expression of ICAM-1, VCAM-1, ELAM-1, E-cadherin and N-cadherin expression on
      human Pca cell lines, Du-145 and PC-3 by flow cytometry. TNF-alpha, IL-10 and IL
      12 were also evaluated. ICAM-1, expressed on PC-3 and DU 145 cells, was enhanced
      by TNF-alpha and IL-10. ELAM-1 was present on DU 145 cells but absent on PC-3.
      TNF-alpha and IL-10 enhanced ELAM-1 on DU 145, but EosA 24 hr supematants failed
      to do so. All three cytokines, namely IL-10, IL-12 and TNF-alpha-induced ELAM-1
      on PC-3 tumor cells. Although VCAM-1 was absent on DU 145 and PC-3 cells, it was
      expressed on DU-145 cells after exposure to EosA: tumor cell co-cultures, and was
      expressed on PC-3 following exposure to IL-10 and IL-12. N-cadherin and E
      cadherin were both expressed on DU-145. While N-cadherin was expressed on PC-3
      cells, E-cadherin was not. N-cadherin was enhanced on DU-145 and PC-3 cells
      following exposure to EosA co-culture and upregulated on PC-3 by IL-10 and EosA
      24 hr supernatants, but decreased by IL-12. E-cadherin was up-regulated on DU 145
      cells following co-culture with EosA and was induced on PC-3 by IL-10 and IL-12,
      but not by EosA co-culture and 24 hr supematants. In conclusion, inflammatory and
      non-inflammatory cytokines modulate CAM expression on Pca cells; EosA and EosA 24
      hr supernatants also exerted modulatory activity of CAM expression. Most
      significantly, the metastasis suppressor molecule, E-cadherin was enhanced on DU
      145 cells by EosA and induced on PC-3 by IL-10 and IL-12 both of which are
      produced by EosA. This suggests potential use of these cytokines in
      immunotherapeutic strategies for prostate cancer and its metastasis.

PMID- 14682383
TI  - Novel ceramide analogues display selective cytotoxicity in drug-resistant breast
      tumor cell lines compared to normal breast epithelial cells.
AB  - The sphingolipid ceramide is involved in diverse cell signaling pathways related
      to proliferation and differentiation. Elevated ceramide also triggers apoptosis.
      Synthetic ceramide derivatives have been shown to be cytotoxic to tumors, yet few
      studies have evaluated whether cytotoxicity of synthetic ceramides is selective
      for tumor cells. We have evaluated the cytotoxic potency of several novel
      ceramide analogues in the drug-resistant breast tumor cell lines, SKBr3 and MCF
      7/Adr, and compared their cytotoxicity in normal breast epithelial cells.
      Cytotoxicity was assessed using release of lactate dehydrogenase into the culture
      medium. (2S, 3S)-3-(6'-Dodecylpyridin-2'-yl)-2-butanoylamidopropane-1,3-diol
      (pyridine-C4-ceramide) produced non-selective cytotoxicity across the three cell
      types (EC50= 12.8-16.7 microM, at 24 hr). However, 2S,5R-2-(octanoylamido-(3E))
      octadecene-1,5-diol (5R-OH-3E-C8-ceramide), (2S,3R)-2-(N-adamantoyl)-(4E)
      octadecen-1,3-diol (adamantyl-ceramide), and (2S,3R)-3-(3'-dodecylphenyl)-2
      butanoylamidopropane-1,3-diol (benzene-C4-ceramide) exhibited increased
      cytotoxicity in the tumor cell lines compared to the normal breast epithelial
      cells. The EC50 values (microM) at 24 hr for these compounds in SKBr3 cells, MCF
      7/Adr cells, and normal breast epithelial cells, respectively, were as follows:
      5R-OH-3E-C8-ceramide, 18.3, 21.2 and 58.7; adamantyl-ceramide, 10.9, 24.9 and
      >100; benzene-C4-ceramide, 18.9, 45.5 and >100. At a concentration of 30 microM,
      the fold increase in cytotoxicity in breast tumor cell lines compared with normal
      breast epithelial cells was as follows: 5R-OH-3E-C8-ceramide, 23.7 and 19;
      adamantyl-ceramide, 11.2 and 10.3 and benzene-C4-ceramide, 79.3 and 77.2, for
      SKBr3 and MCF-7/Adr cells, respectively. Possible mechanisms accounting for
      selectivity are discussed. Ceramide analogues with relatively selective toxicity
      against tumor cells may have potential as therapeutic agents. Elucidating the
      mechanisms of selective cytotoxicity could identify novel targets that may lead
      to development of anti-neoplastic agents with a higher therapeutic index.

PMID- 14682384
TI  - Overexpression of genes involved in vesicular trafficking to the vacuole defends
      against lethal effects of oxidative damage.
AB  - Anticancer bleomycins and structurally-related analogs are oxidative agents that
      mimic ionizing radiation in many of their cellular effects. The current study was
      designed to better understand this class of radiomimetic and oxidative drugs, and
      how cells defend against them to become resistant. Based on some of the
      properties conferred by the blm5-1 mutation of Saccharomyces cerevisiae, a multi
      step cloning strategy was developed to search for genes that protect cells
      against oxidative damage and lethal effects of bleomycin treatments. The strategy
      employed blm5-1 mutant strains to search for genes that rescued the drug
      hypersensitivities conferred by the mutation, and utilized the inability of
      homozygous blm5-1 mutant diploid strains to grow at elevated temperatures. This
      approach identified the VPS3, VPS8 and PEP7 genes that function in vesicular
      trafficking between the endosome and the yeast vacuole via the carboxypeptidase Y
      (CpY) pathway. Mutant blm5-1 strains possess several phenotypic characteristics
      consistent with CpY mutants, including reduced mitotic growth rates and
      sporulative abilities. However, blm5-1 strains were not found to be defective in
      the transport of CpY into the vacuole. We suggest that the ability of the VPS3,
      VPS8 and PEP7 genes to rescue lethal effects of oxidative damage resulted from
      the overexpression of these genes.

PMID- 14682385
TI  - Coadministration of swainsonine and doxorubicin attenuates doxorubicin-induced
      lethality in mice.
AB  - This study in mice concerns the protective effectiveness and mechanisms of action
      by which a coadministered regimen of an immunomodulatory alkaloid swainsonine
      (8alphabeta-indolizidine-1alpha,2alpha,8beta-triol) protects against lethality
      induced by a single bolus intraperitoneal injection of LD50/14 doxorubicin. This
      swainsonine coadministration treatment regimen has been identified previously in
      our laboratory as the superior of the two optimal conditions for diminishing
      lethality in mice due to LD50/14 doxorubicin. The anthracycline, doxorubicin is a
      potent and widely used cancer chemotherapeutic agent whose clinical usefulness is
      limited by both a dose- and time-dependent cardiomyopathy. Specifically, mice
      were given simultaneous injections of swainsonine or its diluent buffer,
      phosphate buffered saline and LD50/14 doxorubicin on day 0, followed by twice
      daily injections of swainsonine or phosphate buffered saline up to day +9. The
      survival and well being of mice were monitored daily for 70 days, which may be
      considered equivalent to a period of 4 to 5 years in humans. This duration has a
      clinical implication with respect to the late manifestation of cardiotoxicity
      after doxorubicin treatment. We quantified the bone marrow cellularity of mice
      and performed in vitro progenitor cell assays to determine the effects of
      swainsonine coadministration treatment regimen on bone marrow competence after
      doxorubicin treatment. The effects of this regimen on doxorubicin-induced changes
      in heart morphology and on hematologic toxicities caused by doxorubicin were
      determined. This swainsonine coadministration treatment regimen significantly
      diminished doxorubicin-induced lethality and prolonged survival and well being of
      mice by preventing bone marrow pancytopenia from the start of therapy. It
      decreased bone marrow toxicity and facilitated its restoration. It accelerated
      restoration of blood hematocrit and total leukocyte levels. Also it facilitated
      the proliferation and differentiation of bone marrow pluripotent stem cells along
      the different paths to progenitor lineages, and significantly preserved the mouse
      heart morphology. These underlying mechanisms of action for the protection by
      swainsonine coadministration strongly suggest a potential role for swainsonine in
      high dose chemotherapy with doxorubicin.

PMID- 14682386
TI  - Pleiotrophic cellular deficiencies conferred by the blm5-1 mutation of
      Saccharomyces cerevisiae.
AB  - Mutational alteration of the BLM5 gene of the model eukaryote, Saccharomyces
      cerevisiae, confers extreme hypersensitivities to lethal effects of ionizing
      radiation, anticancer bleomycins and structurally-related phleomycins. Additional
      properties conferred by the blm5-1 mutation in haploid and diploid strains were
      investigated for the current report. Only one copy of blm5-1 together with the
      normal BLM5 allele was sufficient to produce mitotic and meiotic defects in
      diploids, and greatly increase killing by bleomycin beyond wild type levels.
      Mitotic growth rates of blm5-1/blm5-1 homozygous mutant strains were slower than
      wild type or BLM5/blm5-1 heterozygous strains at 30 degrees C, and growth was
      nearly completely inhibited at 37 degrees C. Meiosis was inhibited at 30 degrees
      C and 37 degrees C in mutant homozygotes, and at 37 degrees C in BLM5/blm5-1
      heterozygotes, while meiosis occurred at equivalent frequencies in wild type
      strains at both temperatures. Surprisingly, mutant strains were found to
      associate extremely low quantities of [S-methyl-3H]bleomycin A2, in contrast to
      normal strains that associated quite high amounts. However, the fractions of the
      total associated radioactivities that were released from normal and blm5-1 cells
      were equivalent. These results suggested that the extremely high killing suffered
      by blm5-1 mutant strains in response to bleomycin treatments results from
      something other than increased intracellular drug concentrations.

PMID- 14682387
TI  - Time and dose-dependent modulation of phase 1 and phase 2 gene expression in
      response to treatment of MCF-7 cells with a natural anti-cancer agent.
AB  - Several known anti-cancer agents have been shown to lead to increased expression
      of phase 2 metabolic enzymes without affecting phase 1 enzymes. Phase 1
      cytochrome P450 (CYP) enzymes are relevant in cancer studies in that they are
      involved in oxidative metabolism, biotransformation and detoxification, whereas
      phase 2 enzyme catalysis leads to clearance. In this study, we obtained semi
      quantitative measurements of cytochrome P450 (phase 1) and phase 2 microsomal
      epoxide hydrolase (mEH) gene expression levels in response to treatment of MCF-7
      breast cancer cells with water-soluble Vernonia amygdalina (V.A.) extract. V.A.,
      a vegetable grown in Nigeria, has potential as an anti-cancer agent. The results
      of Western blot and RT-PCR analyses show that V.A. extract acts as a
      monofunctional inducer within exposure times ranging from 2-16 hr and dose ranges
      from 3-100 microg/ml of V.A. Exposure of cells to low doses of V.A. did not
      affect expression levels of CYP1A1/1A2 mRNA, but lead to induction of mEH, thus
      supporting the chemotherapeutic potential of VA. However, in parallel studies,
      CYP3A4 gene expression was also induced, suggesting potential intermediates which
      influence drug-drug interactions. These data are useful toward further validating
      V.A. extract as a potential clinically useful natural anti-cancer agent and
      provide some support for the concept that modulation in CYP3A4 expression in
      response to treatment is relevant to prognosis.

PMID- 14682388
TI  - The interaction of the steroidal antagonist faslodex and methotrexate.
AB  - Faslodex (FAS, ICI 182, 780), a novel steroidal estrogen antagonist decreased
      high-dose methotrexate (MTX) cytotoxicity in MCF-7 breast cancer cells. When FAS
      is given at least 24 hr prior to MTX, the resultant interaction is antagonistic.
      However, when breast cancer cells are exposed to FAS 24 hr after MTX, the
      interaction between FAS and MTX is not antagonistic. The proliferation of cells
      exposed to 0.1 microM FAS and 10 microM MTX alone or in combination with FAS 24
      hr prior to MTX was in the following order: FAS>FAS 24 hr prior to MTX>MTX. MTX
      administration 24 hr prior to FAS had the following inhibitory effects on the
      growth of cells: MTX 24 hr prior to FAS >MTX>FAS 24 hr prior to MTX>FAS>control
      (no drug exposure). To determine if the antagonistic interaction between FAS and
      MTX was a function of sequence and time, cells were exposed to FAS 24 hr and 36
      hr prior to MTX exposure. The percentages of control rates were 42.70 +/- 4.60%
      and 57.89 +/- 0.55%, respectively, from a 24 hr and 36 hr exposure of FAS prior
      to MTX. The growth rates after 24 and 36 hr exposures to MTX alone were 30.30 +/-
      0.61% and 33.11 +/- 2.57% of control rates, respectively. These studies suggest
      that: a) the interactions between FAS and MTX are sequence-dependent; b) FAS
      antagonizes the effect of MTX when FAS administration precedes MTX, and c) FAS
      antagonism to MTX is a function of time.

PMID- 14682390
TI  - Eosinophils in a tri-cell multicellular tumor spheroid (MTS)/endothelium complex.
AB  - Eosinophils have been found in infiltrates of many different cancers. It is still
      unclear as to whether they are passive bystanders in the cellular milieu or
      active cellular agents in host responses. Thus their harmful or helpful nature
      remains equivocal. We have developed an in vitro tri-cell model of eosinophils,
      MCF-7 breast tumor cell spheroids and HUVEC endothelial cells to examine the
      binding and association of eosinophils with both the tumor and the endothelia and
      the ensuing action of the tumor. Eosinophils bound very rapidly to the tumor
      spheroid and remained tightly bound throughout the 24 hr culture period.
      Histological staining of the tri-cell complex revealed highly granulated
      eosinophils as well as large amounts of degranulated protein diffused throughout
      the spheroid. IL-5 treatment of eosinophil: MTS complexes resulted in destruction
      of the tumor cells, particularly those which had grown out from the spheroid onto
      the endothelial cells. Eosinophils, pretreated with IL-5 before interaction with
      the tumor or endothelial cells, bound aggressively to the endothelial cells,
      thereby preventing tumor attachment. This eosinophil tri-cell tumor model system
      mimics clinical observations with regards to binding to epithelial and
      endothelial cells, dispersal of granular proteins throughout the tumor and also
      tumor destruction. Because it closely mirrors in vivo cellular interactions, it
      allows one to study more closely the mechanism(s) of eosinophil killing, the
      modulation of eosinophil activity and the testing of therapeutic interventions.
      The accommodation of the model to tumor invasion, using metastatic tumor cells
      and extracellular matrices such as matrigel, will help to elucidate a role for
      eosinophils (and their mediators) in cancer invasion and metastasis.

PMID- 14682389
TI  - Arsenic trioxide-induced transcriptional activation of stress genes and
      expression of related proteins in human liver carcinoma cells (HepG2).
AB  - Arsenic is a naturally occurring element, but anthropogenic activities can lead
      to a substantial contamination of the environment. Exposure to arsenic has been
      associated with a significant number of adverse health effects in humans
      including: cardiovascular disease, diabetes, hearing loss, developmental
      abnormalities, anemia, neurologic and neurobehavioral disorder, leukopenia,
      eosinophilia, fibrosis of the liver and the kidney and various neoplasms.
      However, the cellular and molecular events associated with arsenic toxicity are
      poorly understood. Also, the precise mechanisms by which arsenic acts as a
      carcinogen in humans remain to be elucidated. In the present study, we used human
      liver carcinoma (HepG2) cells as a model to study the molecular mechanisms of
      arsenic-induced toxicity and carcinogenesis. We hypothesized that arsenic-induced
      expression of stress genes and related proteins may play a role in the cellular
      and molecular events leading to toxicity and tumorigenesis in liver cells. To
      test this hypothesis, we performed the MTT-assay for cell viability, the CAT-Tox
      (L) assay for gene induction, and the Western Blot analysis to assess the
      expression of cellular proteins including c-fos, HMTIIA, HSP70 and p53. Data
      obtained from the MTT assay indicated a strong dose-response relationship with
      respect to arsenic trioxide toxicity. Upon 48 hr of exposure, the chemical dose
      required to cause 50% reduction in cell viability (LD50) was computed to be 8.55
      +/- 0.58 microg/ml. The CAT-Tox (L) assay showed statistically significant
      inductions (p<0.05) of c-fos, HMTIIA, and HSP70. Western blot analysis also
      demonstrated a dose-response relationship with regard to expression of specific
      cellular proteins. The p53 protein was expressed in arsenic trioxide-treated
      cells, however, the densitometric analysis did not show any significant
      differences (p<0.05) between treated and control cells. The lack of a significant
      induction of p53 may be due to the potential mitogenic effect of arsenic at low
      levels of arsenic exposure.

PMID- 14682391
TI  - Mice primed with swainsonine are protected against doxorubicin-induced lethality.
AB  - The anthracycline, doxorubicin is a potent cancer chemotherapeutic agent whose
      therapeutic usefulness is limited by both a dose- and time-dependent
      cardiomyopathy. We tested the ability of an immunomodulatory alkaloid swainsonine
      (8alphabeta-indolizidine-1alpha,2alpha,8beta-triol) to protect C57BL/6 mice
      against lethality within 70 days following a single bolus intraperitoneal
      injection of LD50/14 doxorubicin. Also, we sought the potential mechanisms
      responsible for this protection. This extended 70-day study in mice, which may be
      considered equivalent to a period of 4 to 5 years in humans, has clinical
      implication for delayed cardiotoxic sequela of therapy with high dose
      doxorubicin. Mice were pretreated with swainsonine or its diluent buffer,
      phosphate buffered saline for ten consecutive days prior to a single bolus
      intraperitoneal injection of a LD50/14 doxorubicin. We have previously defined
      this swainsonine pretreatment regimen as one of the two optimal conditions for
      swainsonine rescue of mice from death induced by LD50/14 doxorubicin. The
      survival and well being of groups of mice pretreated with swainsonine and
      phosphate buffered saline prior to LD50/14 doxorubicin, sham-treated and
      untreated were monitored daily for up to 70 days. The bone marrow cellularity of
      the mice were quantified, and in vitro progenitor cell assays were used to
      determine the effects of these treatment regimens on bone marrow competence
      following doxorubicin treatment. The effects of these treatment regimens on heart
      morphology and hematologic toxicities were also determined. This swainsonine
      pretreatment regimen significantly abrogated doxorubicin-induced lethality and
      prolonged survival of mice by facilitating restoration of bone marrow
      cellularity, accelerating restoration of blood hematocrit and total leukocyte
      levels, enhancing the proliferation and differentiation of bone marrow
      pluripotent stem cells along the different paths to progenitor lineages, and
      preserving the heart morphology. This study strongly suggests a potential role
      for swainsonine with doxorubicin in cancer chemotherapy.

PMID- 14682392
TI  - Low level expression of the HIV-1 Nef protein in transiently transfected COS-1
      cells in culture.
AB  - Nef (negative factor) is a membrane-associated cytoplasmic accessory gene product
      of HIV-1 that induces increased viral load and pathogenesis in the host. In the
      present study, we have utilized a transient co-transfection assay with the HIV
      1lai nef gene and the gene for green fluorescent protein (GFP) in the monkey
      kidney cell line, COS-1, to analyze Nef expression. We have observed
      significantly lower level expression of the Nef protein relative to expression of
      the GFP reporter protein, even when identical vector constructs and similar
      plasmid DNA concentrations were used. Moreover, Northern blot analysis have
      indicated that comparable levels of both the Nef and GFP transcripts were
      transcribed from the co-transfected nef and gfp plasmid constructs, respectively.
      Western blot analysis have also indicated that the intracellular accumulation of
      the Nef protein was not visibly affected by proteolytic inhibitors of two major
      subcellular compartments, lysosomes and proteosomes. In addition, the Nef protein
      does not appear to be secreted into the culture medium up to 24 hr post
      transfection. Our results indicate the possible selective translational
      expression or post-translational down-regulation of the Nef protein in cultured
      COS-1 cells that were transiently co-transfected with the nef and gfp genes.
      However, the mechanism(s) underlying this phenomenon has not been determined.

PMID- 14682393
TI  - A base substitution in the interleukin-10 (IL-10) promoter between Sp1 and ets-1
      binding sites is not associated with variation of IL-10 levels.
AB  - Interleukin 10 (IL-10) may play an important anti-inflammatory and
      immunoregulatory role in asthma. In this study, we investigated the role of a C
      to A substitution at position -627 of the IL-10 promoter, located in a necessary
      transcriptional region, which contains a number of putative transcriptional
      binding sites. The -627 nucleotide position is itself flanked by Sp-1 and ets-1
      binding sites. We studied the allele frequency in 53 unrelated subjects from an
      admixed Caucasian, Asian and Pacific Islander group with personal or family
      histories of asthma. The frequency of homozygous C/C, heterozygous C/A, and
      homozygous A/A alleles at position -627 was 0.28, 0.44 and 0.28, respectively. In
      vitro assays indicated no differences between the C/C and A/A forms in binding
      transcriptional factors, especially Sp-1 factor, or in promoter activity.
      Moreover, in this selected population, there was no association between the C to
      A substitution and serum IL-10 levels. The mean level of IL-10 serum was
      determined to be 3.87 +/- 1.23 pg/ml in subjects carrying the A/A genotype, 3.47
      +/- 0.57 for C/C genotype and 3.13 +/- 0.41 for the heterozygous (C/A genotype).
      This requires confirmation by comparing to non-asthmatic subjects. We conclude
      that although the -627 A allele occurs frequently (50% of alleles) in this
      selected group, in vitro assays and serum IL-10 levels suggest that the -627C-->A
      substitution represents a silent or neutral variant in the IL-10 promoter.

PMID- 14682395
TI  - Characterization and function of the multifaceted peripheral blood basophil.
AB  - Basophils are derived from metachromatic hematopoietic precursor cells of myeloid
      origin. The basophilic granulocyte differentiates and matures in the bone marrow,
      circulates in the peripheral blood, and upon proper stimulation, migrates into
      the tissues. Peripheral blood basophils act as chief effector cells of the
      allergic response and as purveyors of various allergy-associated mediators. Under
      appropriate conditions, basophils can be induced to release their mediators into
      the extracellular space of tissues or blood of the host organism. The plasma
      membrane of basophils contains receptors for immunoglobulin E (IgE)
      homocytotropic antibody which exhibits high affinity for these granulocytes and
      their Fc epsilon receptors. IgE cytophilic antibody binds antigen at its Fab
      portion. When bound to the basophil plasma membrane, the antigen-antibody complex
      undergoes multivalent interactions, which create crosslinking of the Fc epsilon
      receptors on the basophil plasma membrane. This receptor cross-linking results in
      basophil degranulation and subsequent release of its pharmacologically active
      substances. The basophil exhibits considerable heterogeneity and is characterized
      as Type I, II, III, IV, V and VI based upon granule content and time of antigen
      stimulation. Evidence is presented showing the role of the basophil in
      hyperplasia, hypersensitivity, parasitic infections and other diseases.

PMID- 14682394
TI  - Exposure to the anti-TNF-alpha drug thalidomide induces apoptotic cell death in
      human T leukemic cells.
AB  - TNF-alpha is a pro-inflammatory cytokine that plays a key role in disorders due
      to HIV-1 infection and replication such as Kaposi sarcoma, wasting, aphthous
      ulcerations and progression to AIDS. The controversial drug thalidomide is anti
      inflammatory, anti-angiogenic and a selective inhibitor of TNF-alpha that is
      being studied as a treatment for HIV-1-related disorders, immune disorders and
      cancer. The cellular and molecular mechanism of thalidomide is unclear despite
      renewed clinical interest in the drug. Previous data from this laboratory
      indicate that thalidomide decreases cell growth and cell-cell interactions of
      human T leukemic cells. The specific aim of the present study is to determine
      whether thalidomide administration induces cell death via apoptosis. Low dose
      thalidomide treatment of human T leukemic cells exhibited rapid increases in
      caspase-3 activity, annexin V-FITC binding and DNA disintegration that is
      characteristic of apoptosis. These data indicate that low doses of thalidomide
      signal human T leukemic cells to die by apoptosis, which is a possible method of
      altering inflammatory cells and inflammatory activities.

PMID- 14682396
TI  - Partial involvement of c-jun protooncogene in growth enhancing and cytotoxic
      effects of lithium in vitro.
AB  - The AP-1 transcription factor is comprised of homo- and heterodimers of the Fos
      and Jun families of proteins. Literature reports indicate that AP-1 is activated
      in lithium treated mammalian cells suggesting a role in lithium induced growth
      stimulation and apoptosis. In these studies, an antisense c-jun plasmid blocked
      the stimulation of HL-60 cell growth by lithium. Furthermore, antisense c-jun
      caused a 60% reduction in cell viability at 48 hr post-transfection but did not
      influence DNA fragmentation in the presence of lithium. The levels of c-jun mRNA,
      as determined by RT-PCR, were not affected by lithium treatment. Nevertheless, 12
      O-tetradecanoyl-phorbol-13-acetate (TPA) blocked the induction of apoptosis by
      lithium suggesting the involvement of the protein kinase C (PKC) signaling
      pathway. In RAJI cells, antisense c-jun mimicked lithium by inhibiting cell
      proliferation with only a marginal loss in cell viability. This study therefore
      suggests that PKC is involved in the effects of lithium on cells in culture and
      provides evidence for differential effects of antisense c-jun on hemotopoietic
      lineages.

PMID- 14682397
TI  - Differences between patients with non-Hodgkin's lymphomas in a cohort of HIV/AIDS
      patients in Puerto Rico.
AB  - The close association between AIDS and non-Hodgkin's lymphoma (NHL) is well
      known. Few studies are available that evaluate the profile of NHL in a cohort of
      HIV-infected patients who reside in Puerto Rico. The present study was performed
      in a cohort of 2,843 HIV-infected patients followed in the Retrovirus Research
      Center at Bayamon, Puerto Rico, evaluated between January 1992 until December
      2000. NHL prevalence was determined and differences between AIDS defining and non
      AIDS defining NHL were evaluated with the Fisher and ANOVA test. NHL prevalence
      was 0.9%. Nine (33%) were AIDS-defining (AIDS-d) NHL and 18 (67%) were non-AIDS-d
      NHL. Both groups were similar in gender distribution and mean diagnosis age. The
      median CD4+ T cell count at diagnosis was below 150/mm3 in both groups. Injecting
      drug use was higher in AIDS-d NHL patients and Homo-Bisexual contact was higher
      in non-AIDS-d NHL patients. Death rate in the first year after the NHL was 67% in
      the AIDS-d group and 56% in the non-AIDS-d group. AIDS-d NHL incidence decreased
      after the implementation of combined antiretroviral therapy in the cohort, a
      finding not seen in the non-AIDS-d NHL. In summary the study detected low NHL
      prevalence, with high degree of immunological damage at the time of the lymphoma
      diagnosis. Conversely dissimilar response to the antiretroviral therapies was
      also perceived in the incidence of the two NHL groups.

PMID- 14682398
TI  - Efficient gene transfer into human monocyte-derived macrophages using defective
      lentiviral vectors.
AB  - Gene therapy is a promising approach for the treatment of neurological disorders.
      However, current approaches to gene transfer in the central nervous system (CNS)
      are limited by the lack of effective, but non-invasive methods to deliver
      transgenes across the blood-brain barrier (BBB). In an effort to begin to explore
      the use of migratory monocytes as vehicles for delivery of therapeutic and
      antiviral genes into the CNS, we have utilized three HIV-based transfer vectors
      encoding cis-acting elements but lacking either structural genes (gag/pol and
      env), most accessory genes (vif, vpr and nef) and/or rev. These defective
      lentiviral vectors (DLV) encode the green fluorescent protein (GFP), display
      potent antiviral activity in CD4+ lymphocytes and can be mobilized by wild-type
      HIV-1 DLV were generated by transient transfection of 293T cells. Vector titers
      ranged from 4.2-6.6 x 10(6) infectious units (IU)/ml prior to concentration (by
      ultracentrifugation) and were equal to or higher than 1 x 10(9) IU/ml after
      concentration. Primary human monocyte-derived macrophages (MDM) were exposed to
      DLV resulting in efficiencies of transduction ranging from 14 to 26%. GFP
      expression in transduced MDM remained stable for more than 8 weeks without
      apparent cytopathic effect. Given the previously reported antiviral activities of
      these DLV and their lack of cytopathic effects on primary MDM, it may be possible
      to use these vectors to inhibit HIV-1 replication within the CNS.

PMID- 14682399
TI  - Modulation of adhesion molecules and monocyte chemoattractant protein by tumor
      necrosis factor-alpha and salicylic acid in primary human coronary artery
      endothelial cells.
AB  - Kawasaki disease (KD) is an illness characterized by vascular inflammation of
      coronary arteries leading to coronary aneurysms and thromboses. Infiltration of
      immune cells into the intima and adventitia are observed in autopsy tissues of
      patients with KD. Using semi-quantitative RT-PCR and cell-based ELISA, we
      demonstrated that tumor necrosis factor-a induced the expression of intercellular
      adhesion molecules-1 and E-selectin, as well as monocyte chemoattractant protein
      1, in a time- and dose-dependent manner in primary human coronary artery
      endothelial cell cultures. This increase was inhibited by salicylic acid (NaSal),
      and involved the transcription factor NF-kappaB. Based on these data, we suggest
      a pathogenetic mechanism for KD, whereby immune cells are attracted to sites of
      inflammation, undergo extravasation, release enzymes that assist in vascular
      remodeling, thereby weakening the endothelium and hastening the process of
      aneurysm formation. NaSal, in addition to preventing thrombosis and lowering
      fever in KD, may also function in down-regulating adhesion molecules during the
      inflammatory stage of KD.

PMID- 14682400
TI  - Reaching impaired populations with HIV prevention programs: a clinical trial for
      homeless mentally ill African-American men.
AB  - This study tested an intervention to reduce sexual risk behaviors in a high risk
      impaired population: homeless African-American, Caucasian and Hispanic men with
      mental illness. In a comparison group clinical trial, men were assigned to an
      experimental cognitive-behavioral or a control intervention and followed up over
      16 months. Men were recruited from a psychiatric program in two shelters for
      homeless men in Nashville, Tennessee. An ethnically mixed cohort of subjects (54%
      African-American, 42% Caucasian and 4% Hispanic) were included in the study. Most
      had a chronic psychiatric disorder and a co-morbid substance abuse disorder. The
      257 participants who were sexually active (130 experimental, 127 control) prior
      to the trial were the main target of the intervention. An experimental
      intervention (SexG), adapted from Susser and Associates (51), comprised 6 group
      sessions. The control intervention was a 6-session HIV educational program.
      Sexual risk behavior was the primary outcome. The experimental and control groups
      were compared with respect to the mean score on a sexual risk index. Complete
      follow-up data were obtained on 257 men (100%) for the initial six-month follow
      up. These individuals have been followed for the remainder of the 16-month follow
      up. This intervention, (SexG), successfully reduced sexual risk behaviors of
      homeless mentally ill African-American, Caucasian and Hispanic men. Similar
      approaches may be effective in other impaired high-risk populations.

PMID- 14682401
TI  - Lack of enhancement of caprine arthritis encephalitis virus infection in monocyte
      derived macrophage cultures by sera from goats that developed severe arthritis
      after vaccination and virus challenge.
AB  - We examined sera from goats that developed more rapid and severe clinical disease
      after vaccination with inactivated caprine arthritis encephalitis virus (CAEV)
      and virus challenge for CAEV infection-enhancing antibodies. Sera from one
      control and two vaccinated goats were examined for neutralization or enhancement
      of virus infection in caprine macrophages. Macrophage cultures were incubated
      with virus-serum mixtures, then washed and fed with fresh media and incubated.
      Culture fluid was collected at days 2,4 and 8 post-infection and assayed for
      reverse transcriptase (RT) activity. Serum from one of the vaccinated goats
      neutralized virus at 10(-2) and 10(-3) dilutions (p = 0.045 and p = 0.020,
      respectively). The neutralizing effect was lost at higher dilutions (10(-4) and
      10(-5)) of the serum, but no enhancement of infection was seen. Serum from the
      other vaccinated goat did not show any significant neutralizing effect at either
      10(-2) or 10(-3) dilutions and increased infection (40% or greater) at higher
      dilutions, but the increases were not statistically significant. Therefore, there
      was no evidence of virus infection-enhancing activity in these sera that would
      suggest that the severe disease experienced by the vaccinated animals was due to
      serum enhancement of infection. Alternately, the severe arthritis observed could
      have resulted from the pro-inflammatory activities of cytokines and chemokines
      produced by macrophages upon phagocytosis, or receptor-mediated uptake of CAEV
      antibody complexes.

PMID- 14682402
TI  - The association of maternal but not paternal genetic variation in GSTP1 with
      asthma phenotypes in children.
AB  - Maternal factors including atopy and smoking during pregnancy are associated with
      asthma risk during childhood. Suggested mechanisms include transmission of
      specific maternal alleles and maternal influences on the intrauterine
      environment. We have previously shown that polymorphism in glutathione S
      transferase, GSTP1 is associated with airway hyperresponsiveness (AHR) and atopy
      in adults. We now hypothesise that GSTP1 genotypes in the mother and child, but
      not the father, mediate asthma phenotypes in the child. One hundred and forty
      five Caucasian families were recruited via an asthmatic proband aged 7-18 years.
      Atopy and asthma were assessed using a questionnaire, skin prick testing, serum
      IgE, spirometry and methacholine challenge (PC20, dose-response slope--DRS).
      GSTP1 genotyping was determined using PCR. GSTP1 Val105/Val105 genotype in the
      child was associated with a reduced risk of atopy (P = 0.038) and AHR (PC20, P =
      0.046; DRS, P = 0.032). In mothers (P = 0.014) but not fathers (P = 0.623),
      Val105/Val105 was associated with a reduced risk of AHR in the child. We have
      identified, for the first time, an association between maternal genotype and the
      child's asthma phenotype that appears not to be due to transmission of specific
      maternal alleles. This preliminary data supports the view of in utero effects of
      maternal genotype and adds new insights into the possible mechanisms by which
      maternal factors may influence development of childhood asthma.

PMID- 14682403
TI  - Tracheal and lung sounds repeatability in normal adults.
AB  - Tracheal and lung sounds measurements for clinical applications depends on their
      intrasubject repeatability. Our objectives were to characterize tracheal and lung
      sounds and to investigate the temporal variability in normal adults. Tracheal
      sounds were studied in 7 subjects and lung sounds in 10 adults. Acoustic
      measurements were done in five occasions over a month for tracheal sounds and on
      seven occasions over a year for lung sounds. Sounds were recorded using contact
      sensors on the suprasternal notch and on the posterior right lower lobe. Subjects
      breathed through a pneumotachograph at flows of 0.9-1.1 l/s. Signals were low
      pass filtered, amplified and Fourier analysis was applied to sounds within a
      target flow range. We measured the frequencies below which 25% (F25), 50% (F
      median), 75% (F75) and 99% (SEF99) of the spectral power between 100 and 2000 Hz.
      There were no differences between the measurements obtained at different days
      comparing each subject (P = ns, ANOVA). Our results show that the spectral
      pattern of tracheal and lung sounds are stable with low intrasubject variability.

PMID- 14682404
TI  - Endobronchial lesions involved in Mycobacterium avium infection.
AB  - Mycobacterium avium (M. avium) has been described traditionally as an
      opportunistic organism that causes disseminated disease in the human
      immunodeficiency virus (HIV)-positive population and that acts as a pulmonary
      pathogen in patients with underlying lung disease such as chronic obstructive
      pulmonary disease (COPD) or previously diagnosed tuberculosis. Pulmonary
      involvement of M. avium may range from asymptomatic colonization of the airway to
      invasive parenchymal or cavitary disease. However, endobronchial lesions involved
      in M. avium infection are rare in either immunocompetent or immunosuppressed
      hosts. We report here endobronchial mycobacterial infection in a HIV-negative
      patient.

PMID- 14682405
TI  - Effect of iatrogenic haemorrhage on biochemical parameters in pleural effusions.
AB  - AIM: Pleural fluid (PF) samples may become haemorrhagic due to trauma during
      diagnostic procedures. We aimed to evaluate the effect of increasing blood
      concentrations in pleural fluids on biochemical parameters which are used to
      discriminate transudates and exudates. METHODS: Sixty-seven pleural fluid samples
      were separated into five test tubes. Patient's own blood was added in the test
      tubes in different concentrations as follows: No blood in the first tube, 2% in
      the 2nd, 5% in the 3rd, 10% in the 4th, 20% in the 5th tube. RESULTS: After
      addition of blood, statistically significant changes in all biochemical
      parameters in transudate groups were detected. The characteristics changed from
      transudate to exudate 12.9%, 14%, 11.4%, 27% and 14.3% according to Light's
      criteria, serum-PF albumin gradient, cholesterol level, PF/serum cholesterol and
      PF/serum bilirubin, respectively. Results indicating an exudate according to
      Light's criteria were evident only in the 5th tube group, however, when other
      biochemical parameters were used, classification of samples could be altered with
      lower concentrations of blood. CONCLUSION: Contamination of blood, especially in
      borderline transudative pleural effusions, may result in misclassification as an
      exudate. Light's criteria appear to be the least effected and therefore the most
      reliable parameters in bloody effusions.

PMID- 14682406
TI  - Hydrofluoroalkane-134a beclomethasone as a dominant economic asthma therapy.
AB  - Inhaled corticosteroids for asthma treatment have become mainstay of therapy for
      patients with persistent asthma. Numerous inhaled corticosteroids are available
      but to date no prospective cost-effectiveness studies have been reported using
      exclusively US patients and costs. The purpose of this study was to examine the
      cost-effectiveness of HFA-bectomethasone (QVAR) compared to CFC-beclomethasone
      (Vanceril) using data from a year-long prospective randomized, open label,
      parallel multicenter trial. Eligibility criteria required patients to have been
      on a stable dose of CFC-BDP prior to enrollment. Patients were randomized to
      either HFA-BDP at approximately half their previous daily dose of CFC-BDP or to
      continue CFC-BDP Effectiveness data, in terms of symptom-free days (SFDs), were
      used in a cost-effectiveness analysis conducted from the viewpoint of managed
      care. Patients receiving HFA-BDP reported a greater increase (median = 22.1) in
      the number of SFDs than those receiving CFC-BDP (median = 14.3) (P = 0.03). Total
      costs of care were less for patients taking HFA-BDP (median = dollars 668)
      compared to CFC-BDP (median = dollars 977). The median incremental cost
      effectiveness ratio was dollars -5.77 (95% CI: dollars -68.08 to dollars -4.08).
      The results of this analysis indicate that HFA-BDP was a dominant therapy (more
      effective, less costly) compared to CFC-BDP.

PMID- 14682408
TI  - Gene polymorphisms of endothelial nitric oxide synthase enzyme associated with
      pulmonary hypertension in patients with COPD.
AB  - In this cross-sectional controlled study, we aimed to investigate the role of
      polymorphisms of the angiotensin-converting enzyme (ACE) and endothelial nitric
      oxide synthase (eNOS) genes on pulmonary hypertension (PH) in patients with
      chronic obstructive pulmonary disease (COPD). Forty-two (41 male, 1 female, mean
      age: 62 +/- 7 years) COPD patients and 40 (all male, mean age: 60 +/- 8 years)
      healthy controls were included. Respiratory function tests, arterial blood gases,
      and echocardiographic examinations were performed. ACE and eNOS genotypes were
      determined using PCR. The ACE and eNOS genotype distribution was not
      significantly different between COPD patients and controls. On comparing
      pulmonary artery pressures in different eNOS genotypes, the mean pulmonary artery
      pressure (Ppa) in patients with the BB genotype was significantly higher than in
      patients with the nonBB genotypes (41.3 +/- 17.7 mmHg vs. 27.3 +/- 11.2 mmHg, P =
      0.02). However, there was no difference in ACE genotype distributions between
      COPD patients with and without pulmonary hypertension. In stepwise linear
      regression analysis for predicting pulmonary artery pressure, PaO2 and
      polymorphism of eNOS gene were found to be independent variables. In conclusion,
      BB-type polymorphism of the eNOS gene has been associated with PH in addition to
      hypoxemia. However, ACE gene polymorphism was not found to be associated with PH.

PMID- 14682407
TI  - Cardiac or pulmonary dyspnea in patients admitted to the emergency department.
AB  - A simple and quick way of discrimination between cardiac and pulmonary causes of
      dyspnea is essential in patients admitted to the emergency department. We aimed
      to assess the utility of easily applicable diagnostic tools in the differential
      diagnosis of cardiac and pulmonary causes of dyspnea in patients presenting with
      shortness of breath. Clinical and radiologic evaluation, peak expiratory flow
      (PEF), PaO2, PaCO2 measurements were performed in 94 patients admitted to the
      emergency room with dyspnea. All the patients were hospitalized for accurate
      diagnosis and later were categorized into cardiac and pulmonary dyspnea groups.
      PEF, %PEF (percent of predicted PEF), dyspnea differentiation index (DDI = PEF x
      PaO2/1000), %DDI (%PEF x PaO2/1000), PaO2 and PaCO2 measurements were compared
      between the two groups. When cardiac and pulmonary dyspnea groups were compared,
      considering 1.6 as the cut-off value for DDI, measurements above this value imply
      cardiac pathology with 76.7% sensitivity and 67.2% specificity. The sensitivity
      and specificity for cardiac dyspnea calculated according to the cut-off values
      were 96.7% and 40.6% for %DDI; 86.7% and 60.9% for PEF; 86.7% and 54.7% for %PEF;
      66.7 and 68.7 for PaO2. Also for pulmonary dyspnea, sensitivity and specificity
      values for PaCO2 were 50% and 93%. We conclude that DDI, %DDI, PEF, %PEF, PaO2
      and PaCO2 are simple and easily applicable tools for differential diagnosis of
      cardiac and pulmonary dyspnea. Adjunctive utility of these tests in the emergency
      department with clinical and radiologic evaluation contributes to this
      discrimination.

PMID- 14682409
TI  - Assay of pleural fluid interleukin-6, tumour necrosis factor-alpha and interferon
      gamma in the diagnosis and outcome correlation of tuberculous effusion.
AB  - OBJECTIVE: To assess the usefulness of interleukin-6 (IL-6), tumour necrosis
      factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the diagnosis and
      prediction of outcome of pleural tuberculosis. PATIENTS AND METHODS: Pleural
      fluid from 32 TB and 34 non-TB patients was sent for assay of IL-6, TNF-alpha and
      IFN-gamma. Clinical parameters at presentation and residual pleural scarring at
      completion of treatment were assessed for pleural TB cases. RESULTS: The pleural
      fluid Levels of IL-6, TNF-alpha and IFN-gamma in TB patients were significantly
      higher than those with non-TB effusions (P values of <0.001, 0.018 and <0.001,
      respectively by independent t-test). Utility of these cytokines for diagnosis of
      pleural TB was evaluated using receiver operating characteristic (ROC) curve
      analysis. The cut-off values for IL-6, TNF-alpha and IFN-gamma determined in this
      analysis were 4000, 4 and 60 pg/ml respectively, and their sensitivity and
      specificity were 90.6% and 76.5%, 90.6% and 79.4%, 100% and 100%, respectively.
      The pretreatment pleural fluid IL-6 levels had a positive correlation with the
      number of febrile days after treatment (Pearson correlation test: r=0.60,
      P=0.009). A negative correlation was found between the percentage reduction in
      pleural fluid cytokines after 2 weeks treatment and the extent of residual
      pleural scarring (IL-6: r=-0.62, P=0.041; TNF-alpha: r=-0.65, P=0.030; IFN-gamma:
      r=0.83, P=0.002). CONCLUSION: Pleural fluid IL-6, TNF-alpha and IFN-gamma assays
      are useful in the diagnosis of pleural TB. The initial IL-6 level correlates with
      the number of febrile days. The percentage change of cytokines after 2 weeks of
      treatment also helps to predict residual pleural scarring.

PMID- 14682410
TI  - Exercise testing as a predictor of surgical risk after pneumonectomy for
      bronchogenic carcinoma.
AB  - The aim of the present investigation was to evaluate the predictive value of a
      symptom-limited exercise test in predicting postoperative morbidity and mortality
      in patients submitted to pneumonectomy. The study was conducted in 150 patients
      (mean age, 57.1). Forty-four patients (29.3%) had postoperative complications.
      Four patients (2.7%) died within one month of the pneumonectomy. Patients with
      complications had significantly lower VO2max. The incidence of complications in
      relation to the amount of oxygen consumption showed that with the progressive
      decrease of oxygen consumption there was a progressive increase in frequency of
      complications. In particular patients with VO2max < 50% of predicted should be
      considered at high risk of morbidity and mortality from cardiopulmonary causes.
      This predictive capacity of VO2max was more evident in patients with a
      preoperative FEV1 less than 70% of predicted. The present data support the
      suggestion that exercise testing could be a useful adjunt in the evaluation of
      postoperative risk for pneumonectomy, especially in patients with obstructive
      pulmonary disease.

PMID- 14682411
TI  - High levels of interleukin-6 in the exhaled breath condensate of patients with
      COPD.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by
      chronic inflammation of the respiratory tract. METHODS: We investigated the
      presence of interleukin-6 (IL-6: a cytokine secreted by monocytes/macrophages, T
      cells, B cells, fibroblasts, bone marrow stromal cells, keratinocytes and
      endothelial cells) in the exhaled breath condensate of 16 exsmokers with moderate
      COPD, 12 healthy non-smokers. IL-6 was measured by means of a specific enzyme
      immunoassay. RESULTS: IL-6 levels were detectable in all of the subjects, but
      were higher in the COPD patients (8.0 +/- 0.1 pg/ml; P < 0.0001) than in the
      healthy non-smokers (4.9 +/- 0.2 pg/ml) with a correlation in this group between
      age and IL-6 levels (r = 0.597; P < 0.05). CONCLUSIONS: The increased IL-6 levels
      in exhaled breath condensate may reflect airway inflammation in patients with
      COPD.

PMID- 14682412
TI  - Short- and long-term efficacy of fluticasone propionate in subjects with early
      signs and symptoms of chronic obstructive pulmonary disease. Results of the DIMCA
      study.
AB  - BACKGROUND: Early treatment with inhaled corticosteroids may prevent progression
      of irreversible obstruction in COPD, especially in patients with bronchial
      hyperresponsiveness. We investigated the clinical effects of early introduction
      of inhaled steroids in subjects showing early signs and symptoms of COPD without
      a prior clinical diagnosis. METHODS: Study subjects were detected in a general
      population screening and monitoring program. Those with a moderately accelerated
      annual FEV1 decline and persistent respiratory symptoms were invited to
      participate in a 2-year randomized controlled trial comparing fluticasone
      propionate DPI 250 microg b.i.d. with placebo. Pre- and post-bronchodilator (BD)
      FEV1, PC20 histamine, functional status (COOP/WONCA charts) and occurrence of
      exacerbations were periodically assessed. Subjects recorded respiratory symptoms.
      Post-BD FEV1 decline served as the main outcome. Multivariable repeated
      measurements analysis techniques were applied. RESULTS: 48 subjects were
      randomized (24 fluticasone, 24 placebo). After 3 months, the post-BD FEV1 had
      increased with 125 ml (SE = 68, P = 0.075) and the pre-BD FEV1 with 174 ml (SE
      90, P = 0.059) in the fluticasone relative to the placebo group. The subsequent
      post-BD and pre-BD FEV1 decline were not beneficially modified by fluticasone
      treatment. There were no statistically significant differences in respiratory
      symptoms, functional status, or exacerbations favoring fluticasone. Subgroup
      analysis indicated that the presence of bronchial hyperresponsiveness modified
      the initial FEV1 response on fluticasone, but not the subsequent annual FEV1
      decline. CONCLUSION: Early initiation of inhaled steroid treatment does not seem
      to affect the progressive deterioration of lung function or other respiratory
      health outcomes in subjects with early signs and symptoms of COPD. In subjects at
      risk for, or in an early stage of COPD, long-term inhaled steroid treatment
      should not be based on a single spirometric evaluation after 3 months.

PMID- 14682413
TI  - Comparative efficacy of once-daily therapy with inhaled corticosteroid,
      leukotriene antagonist or sustained-release theophylline in patients with mild
      persistent asthma.
AB  - The purpose of this study was to compare the efficacy and safety of the inhaled
      budesonide, sustained-release theophylline and montelukast, a leukotriene
      receptor antagonist, in patients with mild persistent asthma. In this single
      center, randomized, parallel-group study that not designed blindly and placebo
      controlled manner, 74 patients with mild persistent asthma were treated with
      either inhaled budesonide 400 microg once daily, oral montelukast 10 mg once
      daily, or sustained-release theophylline 400 mg once daily for 3 months. In all
      three treatment groups, improvements were attained in overall asthma control.
      Asthma symptom scores and supplemental beta2-agonist use were quite the same in
      all three treatment groups (P>0.05). Although inhaled budesonide group resulted
      in significantly greater improvements compared with the other two groups in the
      lung functions (P<0.05), the changes in FEV1 and PEF are within the baseline
      variability and there was no statistically significant difference among the
      groups when analyzed by treatment month (P>0.05). Exacerbations of asthma were
      experienced by 16% of the patients in the montekulast group, by 12.5% of the
      patients in the theophylline group, and by none of the patients in the budesonide
      group. The adverse event in each of the three groups was 12%, 16% and 16.7%,
      respectively. It is concluded that the most important clinical parameters do not
      point that one of the treatments is more effective than others. Treatment with
      inhaled corticosteroid is preferred, but sustained-release theophylline and
      leukotriene antagonists are alternative controller medications in mild persistent
      asthma.

PMID- 14682414
TI  - Home mechanical ventilation for restrictive thoracic diseases: effects on patient
      quality-of-life and hospitalizations.
AB  - Forty-five patients with restrictive respiratory diseases, including thoracic
      wall diseases (TWD, n = 27) and neuromuscular diseases (NMD, n = 18), underwent
      18 months of home mechanical ventilation (HMV) treatment. Treatment consisted of
      a two-level pressure system for 7h at night, with oxygen available if needed.
      Questionnaire-based assessments of health-related quality-of-life (HRQL) were
      evaluated before treatment and at 3, 6, 9, 12 and 18 months of follow-up.
      Hospitalization rates pre- and post-treatment were recorded, and the numbers need
      to treat (NNT) to avoid hospitalization and absolute risk reduction (ARR) rates
      were calculated. Several categories of HRQL, including physical function and
      vitality, improved significantly with treatment in both groups of patients; these
      improvements persisted over the entire 18 months. In contrast, other categories
      such as social function and mental health improved initially and declined
      subsequently. Hospitalizations decreased significantly with treatment. NNT
      calculations indicated that treatment would be needed for two TWD patients (ARR
      63%) and one NMD patient (ARR 78%) to prevent one hospitalization per year per
      disease group. We conclude that improved quality-of-life and decreased
      hospitalizations make home non-invasive mechanical ventilation an useful
      treatment for patients with restrictive respiratory disorders.

PMID- 14682415
TI  - History of the American Institute of Ultrasound in Medicine's efforts to keep
      ultrasound safe.

PMID- 14682416
TI  - Does low-energy ultrasound, known to enhance thrombolysis, affect the size of
      ischemic brain damage?
AB  - OBJECTIVE: In view of the potentially beneficial effects of ultrasound on
      fibrinolysis, we aimed to study possible drawbacks of low-energy ultrasound on
      nonperfused and perfused brain tissue. METHODS: A model of transient focal
      ischemia in anesthetized rats was used. Rats were randomly assigned to 1 of 3
      groups: the first exposed to ultrasound, the second a control of the ultrasound
      group, and the third a method control group. In each group, the right middle
      cerebral artery was occluded for 1.5 hours, during which time the rats in the
      ultrasound group were exposed to 1 hour of pulsed ultrasound (1 MHz; spatial
      average temporal-average intensity, 0.1 W/cm2 at a duty cycle of 10%). The
      occlusion period was followed by a 24-hour recirculation period, after which the
      brains were excised and evaluated. RESULTS: Ultrasound did not affect the volume
      of ischemic damage in nonperfused brain tissue or add ischemic damage to perfused
      brain tissue. CONCLUSIONS: Under these experimental conditions, ultrasound does
      not cause additional ischemic damage to the rat brain during middle cerebral
      artery occlusion.

PMID- 14682417
TI  - Value of power Doppler imaging and the hypoechoic halo in the sonographic
      detection of foreign bodies: correlation with histopathologic findings.
AB  - OBJECTIVE: To present the power Doppler findings and evaluate the hypoechoic rim
      in increasing the conspicuity of foreign bodies detected on sonography and to
      correlate the sonographic and histopathologic findings. METHODS: Between 1998 and
      2001, all sonographic examinations for evaluation of possible foreign bodies were
      reviewed retrospectively. Patients who had surgical exploration and pathologic
      evaluation were included in the study. Gray scale and power Doppler examinations
      were performed with high-frequency linear array transducers. Histologic
      evaluation was then correlated with the sonographic findings. RESULTS: Twenty
      five patients were referred for evaluation of possible foreign bodies. Twelve
      patients underwent surgery and had pathologic correlation. Sonography had
      sensitivity of 92% for the overall detection of foreign bodies. There were 2
      false-positive findings in which discrete foreign bodies were not seen at gross
      inspection, but inflammation and scar tissue were present at histologic
      examination. Pathologic findings were thought to represent chronic foreign body
      reactions. Hypervascularity immediately surrounding the foreign bodies was shown
      on power Doppler imaging in all cases, correlating with granulation tissue and
      neovascularity on pathologic examinations. The hypoechoic halo was shown in all
      but 2 cases and correlated with fibrinous exudate, granulation tissue, and
      collagenous capsule formation. CONCLUSIONS: Sonography is an effective and
      sensitive tool for the detection of soft tissue foreign bodies. The use of power
      Doppler imaging may aid in detection of possible foreign bodies by increasing the
      conspicuity of both the hypoechoic halo and the foreign body itself.

PMID- 14682418
TI  - Sonographic evaluation of primary peripheral nerve repair.
AB  - OBJECTIVE: This feasibility study was undertaken to define the potential of
      sonography for the follow-up evaluation of patients with surgical repair after
      nerve transection and persistent impairment of nerve function. METHODS: Nineteen
      patients with primary repair of a transected peripheral nerve because of direct
      trauma or complex fractures were evaluated with sonography. All patients had
      persistent clinical symptoms and neurologic signs of impaired nerve function. In
      11 patients who underwent second operations, the intraoperative findings were
      correlated with those of sonography. RESULTS: Reliable identification of repaired
      nerves with sonography was feasible in all patients. However, in some cases,
      sufficient visualization of the site of nerve coaptation was problematic because
      of extensive scarring. Sonographic findings included the appearance of partial
      discontinuity of nerve fascicles, detection of neuromas, and compression of
      nerves by overlying scars. Surgical correlation with sonographic findings was
      excellent for neuroma detection; however, definition of nerve continuity on
      sonography was sometimes impaired by scarring. CONCLUSIONS: Sonography has a high
      potential for follow-up examinations of peripheral nerves in relation to previous
      nerve repair in patients with persistent neurologic signs and symptoms of nerve
      impairment. Sonography may help in decisions for follow-up surgery by identifying
      lesions such as neuromas in continuity or discontinuous nerve elements--lesions
      that will possibly benefit from a second look.

PMID- 14682419
TI  - Sonography of partial-thickness quadriceps tendon tears with surgical
      correlation.
AB  - OBJECTIVE: With the use of surgical findings as the reference standard, the
      purpose of this study was to describe the sonographic findings of partial
      thickness and complete tears of the quadriceps tendon and to determine whether
      sonography can potentially aid diagnosis. METHODS: Three hundred eighty-nine
      consecutive sonographic reports (January 1996 to April 2001) of the
      knee/quadriceps tendon were reviewed retrospectively and assessed for subsequent
      surgery on the quadriceps tendon. Seven cases were thus identified. Findings at
      surgery (complete versus partial tears) were compared with the original
      sonography reports. RESULTS: All 4 partial tears and 1 of 2 complete tears were
      diagnosed correctly on the basis of sonography. One complete tear was described
      as a partial tear on the basis of sonography. In a seventh case, complete
      disruption of the extensor mechanism with osseous avulsion of the superior pole
      of the patella was identified correctly. Dynamic scanning was essential in
      diagnosing a partial quadriceps tendon tear in 1 case. CONCLUSIONS: Sonography,
      including the use of dynamic evaluation, was helpful in the diagnosis of partial
      thickness tears of the quadriceps tendon and may aid in differentiation of such
      cases from complete quadriceps tendon tears, particularly in the acute setting.
      The presence of scar tissue in the setting of chronic injury may represent a
      potential pit-fall in the assessment of partial versus complete quadriceps tears.
      Further study is needed to define the accuracy of sonography for detecting
      quadriceps tendon tears.

PMID- 14682420
TI  - Spectral Doppler sonography of musculoskeletal soft tissue masses.
AB  - OBJECTIVE: To determine whether resistive indices obtained from spectral Doppler
      waveforms can be used to distinguish benign from malignant musculoskeletal soft
      tissue masses. METHODS: A retrospective review of Doppler sonograms was performed
      for 52 patients with 53 soft tissue masses. All masses showed internal flow on
      color or power Doppler sonography, and spectral Doppler sonography yielded
      waveforms from which resistive indices were calculated. This information was
      analyzed along with the histologic diagnosis of each lesion with significance set
      at P > .05. RESULTS: There were 19 benign lesions and 34 malignancies. The
      resistive indices of the benign masses ranged from 0.44 to 1.0 (mean +/- SD, 0.72
      +/- 0.42), whereas the malignant masses had resistive indices ranging from 0.28
      to 1.0 (mean, 0.62 +/- 0.36). There was no statistically significant (P > .05)
      difference between the resistive indices of benign and malignant lesions.
      CONCLUSIONS: Resistive indices cannot be used to distinguish benign from
      malignant musculoskeletal soft tissue masses.

PMID- 14682421
TI  - Reproducibility of heel ultrasound measurement in prepubescent children: lack of
      influence of ethnicity, sex, or body size.
AB  - OBJECTIVE: There is a growing demand for assessment of bone status in children.
      Among the techniques currently available, quantitative ultrasound measurement is
      attractive because of its lower cost, portability, and safety. However, factors
      influencing its reproducibility in children remain an issue. This study was
      designed to evaluate the effects of ethnicity, sex, and body size on the short
      term reproducibility of heel ultrasound measurement in children. METHODS: We
      studied 59 prepubescent children, 36 white (23 girls and 13 boys) and 23 black (9
      girls and 14 boys), 5 to 12 years of age. On the same day, each child underwent
      triplicate measurement with an ultrasonometer and was repositioned after each
      measurement. RESULTS: The precision error of the stiffness index expressed as a
      percentage of the coefficient of variation was generally good. There was no
      difference between ethnicity or sex. Respectively, the average values were 3.81%
      and 3.86% in white girls and boys and 3.64% and 3.51% in black girls and boys.
      Height, weight, and body mass index were not found to affect this
      reproducibility. CONCLUSIONS: These data support the reliability and usefulness
      of ultrasound for assessment of pediatric bone status.

PMID- 14682422
TI  - Umbilical cord morphologic characteristics and umbilical artery Doppler
      parameters in intrauterine growth-restricted fetuses.
AB  - OBJECTIVE: To compare prenatal morphometric changes of umbilical cord components
      in intrauterine growth-restricted fetuses with and without abnormal umbilical
      artery Doppler parameters. METHODS: Consecutive singleton intrauterine growth
      restricted fetuses at a gestational age of older than 20 weeks were compared with
      matched appropriate-for-gestational-age fetuses. Intrauterine growth restriction
      was defined in the presence of a sonographic abdominal circumference below the
      5th percentile for gestational age at the time of sonography and a birth weight
      below the 10th percentile. The sonographic examination included pulsed Doppler
      measurements of the umbilical artery resistance index and measurements of the
      umbilical cord cross-sectional area and the umbilical cord vessel area. RESULTS:
      A total of 84 intrauterine growth-restricted fetuses and 168 appropriate-for
      gestational-age fetuses were included in the study. All umbilical cord components
      (umbilical cord cross-sectional area, vein area, artery area, and Wharton jelly
      area) were smaller in the intrauterine growth-restricted fetuses. The prevalence
      of lean umbilical cords (cross-sectional area < 10th percentile for gestational
      age) was significantly higher in intrauterine growth-restricted fetuses compared
      with appropriate-for-gestational-age fetuses (73.8% versus 11.3%; P < .0001). A
      significant and progressive reduction of the umbilical vein area corresponding to
      the degree of umbilical artery Doppler parameter abnormality was found. The
      umbilical artery area was not related to the hemodynamic changes of the blood
      flow in the umbilical arteries. CONCLUSIONS: The proportion of lean umbilical
      cords was higher in intrauterine growth-restricted fetuses than in appropriate
      for-gestational-age fetuses. Umbilical vein caliber decreases significantly with
      worsening of umbilical artery Doppler parameters.

PMID- 14682423
TI  - Transrectal ultrasonography for problem solving after transvaginal
      ultrasonography of the female internal reproductive tract.
AB  - OBJECTIVE: To report the value of transrectal ultrasonography of the female
      internal reproductive tract as a complementary problem-solving technique after
      transvaginal ultrasonography in selected patients. To date, transrectal
      ultrasonography of the female internal reproductive tract has been advocated in
      lieu of transvaginal ultrasonography for women in whom transvaginal
      ultrasonography cannot be performed for various reasons. METHODS: Ten
      illustrative cases are presented of women for whom transrectal ultrasonography
      performed after transvaginal ultrasonography provided additional clinically
      important information regarding the female internal reproductive tract. RESULTS:
      Transrectal ultrasonography was helpful in 2 scenarios: (1) women with a
      retroverted uterus in whom the endometrial stripe was virtually parallel to the
      ultrasound beam and thus could not be properly measured on transvaginal
      ultrasonography, and (2) women in whom normal or pathologic adnexal findings were
      distant from the vagina or obscured by intervening structures during transvaginal
      ultrasonography but were near the rectum or not obscured during transrectal
      ultrasonography. In 1 case, transrectal ultrasonography yielded a diagnosis of
      ectopic pregnancy that was missed prospectively on transvaginal ultrasonography
      because pain severely limited the examiner's ability to manipulate the
      transvaginal ultrasound transducer. CONCLUSIONS: Transrectal ultrasonography of
      the female internal reproductive tract can provide clinically useful information
      to complement transvaginal ultrasonography in selected patients.

PMID- 14682424
TI  - Perinatal three-dimensional color power Doppler ultrasonography of vein of Galen
      aneurysms.
AB  - OBJECTIVE: To present the prenatal and postnatal three-dimensional color power
      Doppler ultrasonographic features in cases of vein of Galen aneurysmal
      malformation. METHODS: Prenatal three-dimensional color power Doppler
      ultrasonography was used to image the neurovascular malformations in 3 fetuses
      with vein of Galen aneurysms and in unaffected control fetuses at the same
      gestational age. Postnatal transfontanel three-dimensional power Doppler
      ultrasonography was also performed in the third affected case and in an
      unaffected control neonate. The feeding and drainage vessels were analyzed in the
      three-dimensional rendering mode. RESULTS: The first case was complicated by
      porencephaly and fetal heart failure, and the pregnancy was terminated. The other
      2 cases were uncomplicated prenatally, but 1 of the infants died after aneurysmal
      embolization due to acute cerebral ischemia. The angioarchitecture of the
      arteriovenous fistula was characterized in greater detail by three-dimensional
      color power Doppler ultrasonography than by two-dimensional ultrasonography,
      especially regarding the anatomic features of the feeding and drainage vessels
      and their connections with the dilated vein of Galen. CONCLUSIONS: Three
      dimensional color power Doppler ultrasonography provided detailed images of the
      aneurysmal malformation and its vascular connections. Further studies are needed
      to correlate three-dimensional vascular imaging patterns with outcome.

PMID- 14682425
TI  - Prenatal diagnosis of aneurysms of the vein of Galen (vena magna cerebri) with
      conventional sonography, three-dimensional sonography, and magnetic resonance
      imaging: report of 2 cases.
AB  - OBJECTIVE: To describe the cases of 2 fetuses with aneurysms of the vein of Galen
      diagnosed prenatally. METHODS: The techniques used were conventional sonography,
      three-dimensional sonography, and ultrafast magnetic resonance imaging. On the
      basis of these imaging modalities, prognostic factors, such as drainage and
      secondary damage, were assessed. RESULTS: The first fetus had good prognostic
      indices, and embolization after birth was successful. According to the prognostic
      factors, a poor neonatal outcome was predicted for the second fetus. The neonate
      died soon after birth. CONCLUSIONS: Conventional sonography, color Doppler
      imaging, and magnetic resonance imaging appeared to be useful diagnostic tools.
      The prognostic factors can be useful in counseling patients and providing the
      best possible care after birth.

PMID- 14682426
TI  - Sonographic evaluation of lower extremity interosseous membrane injuries:
      retrospective review in 3 patients.
AB  - OBJECTIVE: To describe the sonographic findings of lower extremity interosseous
      membrane disruption with computed tomographic and surgical correlation. METHODS:
      Three patients with sonographic evaluation of the lower extremity interosseous
      membrane were identified through the clinical experience of 1 author over a 5
      year period. Sonographic images of the symptomatic and unaffected lower
      extremities were retrospectively characterized and correlated with computed
      tomographic and surgical findings by 2 fellowship-trained musculoskeletal
      radiologists. RESULTS: The normal interosseous membrane was identified in the
      asymptomatic lower extremities in all 3 patients, which appeared as a thin,
      hyperechoic (nearly equal to bone cortex) line, continuous from the tibia to the
      fibula. The abnormal interosseous membrane in all 3 cases appeared abnormally
      hypoechoic, poorly defined, and discontinuous at the tibia. A proximal fibular
      fracture was shown on sonography in 1 of 3 symptomatic lower extremities with
      radiographic evidence of a fracture. The sonographic findings correlated with the
      computed tomographic images. Distal tibiofibular syndesmosis injuries were
      confirmed and treated at surgery in 2 patients. CONCLUSIONS: Sonography can show
      both normal and injured interosseous membranes of the lower extremity, as well as
      associated proximal fibular fractures.

PMID- 14682427
TI  - Median arcuate ligament syndrome.
AB  - OBJECTIVE: To describe the importance of obtaining erect views when evaluating
      the celiac artery with sonography. METHODS: Two patients had duplex and color
      flow Doppler sonographic evaluations of the celiac artery, including inspiration,
      expiration, and erect views. RESULTS: Both patients had elevated celiac artery
      velocities with inspiration and expiration. These results alone would suggest
      celiac artery stenosis. With erect views, the celiac artery velocities returned
      to normal. The addition of erect views allowed the correct diagnosis of median
      arcuate ligament syndrome to be made. CONCLUSIONS: When evaluating the celiac
      artery, it is important to include erect views to prevent misdiagnosis of celiac
      artery stenosis.

PMID- 14682428
TI  - Clinically unsuspected foreign bodies: the importance of sonography.
AB  - OBJECTIVE: To show the value of sonography in the detection of clinically
      unsuspected foreign bodies appearing as soft tissue masses. METHODS: High
      resolution B-mode and color Doppler sonography was performed in 288 patients
      referred with superficial soft tissue masses over a period of 2 years. RESULTS:
      In 8 lesions in 6 patients, sonography showed small curved or linear echogenic
      structures surrounded by hypoechoic masses characteristic of foreign bodies with
      granulation tissue. One lesion had increased vascularity on color Doppler
      sonography. Patients were referred for other imaging studies, including magnetic
      resonance imaging, computed tomography, and bone and labeled red blood cell
      scintigraphy, which did not add relevant information. Three patients underwent
      surgery; foreign bodies were found in 2, and infected granulation tissue was
      found in 1. Spontaneous resolutions and no growth of the lesions were seen in the
      other 2 patients. CONCLUSIONS: The possibility of a foreign body should be
      considered when scanning soft tissue masses even in the absence of a relevant
      clinical history. Once a foreign body is diagnosed, no further workup is
      indicated.

PMID- 14682429
TI  - Subcutaneous fat necrosis: hypoechoic appearance on sonography.

PMID- 14682430
TI  - Spontaneous occlusion of a traumatic false aneurysm of the peroneal artery.

PMID- 14682431
TI  - Vein of galen malformation: prenatal evaluation with three-dimensional power
      Doppler angiography.

PMID- 14682432
TI  - Prenatal diagnosis of an intracranial arteriovenous fistula in the posterior
      fossa on the basis of color and three-dimensional power Doppler ultrasonography.

PMID- 14682433
TI  - Transvaginal sonographic findings in diagnosis and treatment of urethral
      stricture.

PMID- 14682434
TI  - Twinkling artifact related to intravesicular suture.

PMID- 14682435
TI  - Sonographic features of primary testicular granulocytic sarcoma.

PMID- 14682437
TI  - The sonographer practitioner and advanced practice sonographer.

PMID- 14682436
TI  - Orchiopexy: a cause of benign testicular lobulation.

PMID- 14682438
TI  - Smoking and cervical cancer: pooled analysis of the IARC multi-centric case-
      control study.
AB  - BACKGROUND: Smoking has long been suspected to be a risk factor for cervical
      cancer. However, not all previous studies have properly controlled for the effect
      of human papillomavirus (HPV) infection, which has now been established as a
      virtually necessary cause of cervical cancer. To evaluate the role of smoking as
      a cofactor of progression from HPV infection to cancer, we performed a pooled
      analysis of 10 previously published case-control studies. This analysis is part
      of a series of analyses of cofactors of HPV in the aetiology of cervical cancer.
      METHODS: Data were pooled from eight case-control studies of invasive cervical
      carcinoma (ICC) and two of carcinoma in situ (CIS) from four continents. All
      studies used a similar protocol and questionnaires and included a PCR-based
      evaluation of HPV DNA in cytological smears or biopsy specimens. Only subjects
      positive for HPV DNA were included in the analysis. A total of 1463 squamous cell
      ICC cases were analyzed, along with 211 CIS cases, 124 adeno- or adeno-squamous
      ICC cases and 254 control women. Pooled odds ratios (OR) and 95% confidence
      intervals (CI) were estimated using logistic regression models controlling for
      sexual and non-sexual confounding factors. RESULTS: There was an excess risk for
      ever smoking among HPV positive women (OR 2.17 95%CI 1.46-3.22). When results
      were analyzed by histological type, an excess risk was observed among cases of
      squamous cell carcinoma for current smokers (OR 2.30, 95%CI 1.31-4.04) and ex
      smokers (OR 1.80, 95%CI 0.95-3.44). No clear pattern of association with risk was
      detected for adenocarcinomas, although the number of cases with this histologic
      type was limited. CONCLUSIONS: Smoking increases the risk of cervical cancer
      among HPV positive women. The results of our study are consistent with the few
      previously conducted studies of smoking and cervical cancer that have adequately
      controlled for HPV infection. Recent increasing trends of smoking among young
      women could have a serious impact on cervical cancer incidence in the coming
      years.

PMID- 14682439
TI  - Parental and birth characteristics in relation to testicular cancer risk among
      males born between 1960 and 1995 in California (United States).
AB  - OBJECTIVE: We explored birth and parental risk factors for testicular cancer,
      examining risk factors for all testicular cancers and by histologic type.
      METHODS: We linked 1645 testicular cancer cases to live singleton birth
      certificates, selecting three random controls per case, matched by sex and date
      of birth. We used conditional multiple logistic regression to assess the mutually
      adjusted effects of parental and birth characteristics on testicular cancer risk.
      RESULTS: Sons of Black mothers had a lower risk than those of White mothers
      (adjusted odds ratio (AOR) = 0.38, 95% confidence interval (CI)=0.12, 1.22).
      Increasing maternal age was associated with an increased risk in offspring
      (AOR=1.03 for each year of maternal age, 95% CI=1.01, 1.05). Sons of primiparous
      and low-multiparous women had increased risks compared to sons of high
      multiparous women (AOR=1.22, 95% CI=1.04, 1.44; and AOR=1.31, 95% CI=1.12, 1.54,
      respectively). Among seminomas, term infants with birth weights of 1500-2499 g
      had a higher risk compared to term, normal birth weight infants (AOR=2.69, 95%
      CI=1.40, 5.17; p-value for homogeneity=0.008). CONCLUSIONS: Markers of higher
      estrogen exposure in the mother (age and parity) are associated with increased
      testicular cancer risk, and factors associated with fetal growth retardation may
      be associated with seminoma testicular cancer.

PMID- 14682440
TI  - Methyl-group dietary intake and risk of breast cancer among African-American
      women: a case-control study by methylation status of the estrogen receptor alpha
      genes.
AB  - OBJECTIVES: Recent molecular studies show that the absence of estrogen receptor
      (ER) alpha gene expression in breast cancer is associated with methylation of the
      CpG island located in the 5' region and the first exon of the ER alpha gene.
      Because CpG island methylation is an early event in carcinogenesis and because a
      methyl-deficient diet may lead to abnormal DNA methylation including CpG island
      methylation, we hypothesized that a methyl-deficient diet is more likely to be
      associated with breast cancer with methylated ER alpha gene CpG islands. This
      study aimed to test this hypothesis in African-American women using a case
      control design. METHODS: Cases were 304 African-American women pathologically
      diagnosed with breast cancer during 1995-1998 who lived in three Tennessee
      counties. Controls were 305 African-American women without breast cancer, who
      were selected through random-digit dialing and frequency matched to cases by 5
      year age range and county of residence. Information on dietary intake and other
      risk factors was collected through telephone interviews. Dietary methyl
      components were defined based on folate and methionine intakes and alcohol
      consumption. Tumor tissue samples were collected for measuring methylation status
      of the ER alpha gene. RESULTS: Our results showed that the odds ratio (OR)
      estimates for lower dietary folate intake were 2.0 (95% confidence interval, CI:
      0.8-4.8) for cases with a methylated ER alpha gene, 0.6 (95% CI: 0.3-1.5) for
      cases with an unmethylated ER alpha gene, and 1.6 (95% CI: 0.7-3.8) for cases
      with unknown methylation status (presumably including cases with both methylated
      and un-methylated genes). However, low methionine intake appeared more likely to
      be associated with tumors with unknown methylation status and high level of
      alcohol consumption seemed more likely to be related to tumors with un-methylated
      genes. CONCLUSIONS: These results did not show a pattern consistent with the
      study hypothesis that methyl-deficient diets are more likely related to breast
      cancer with a methylated ER gene.

PMID- 14682441
TI  - Risk factors for anal cancer: results of a population-based case--control study.
AB  - OBJECTIVE: Although the incidence of anal cancer is higher in women than in men,
      the reasons for this gender difference are not clear. The purpose of this study
      was to identify risk factors for anal cancer in both men and women. METHODS: We
      conducted in-person interviews with 102 males and 106 females with squamous or
      transitional cell carcinoma of the anus and 208 individually matched controls.
      RESULTS: Compared with persons who had never experienced receptive anal
      intercourse, those who had experienced it more than 130 times were 18 times as
      likely to develop anal cancer (adjusted odds ratio [OR] = 17.6 (95% confidence
      interval [CI] = 1.3-234). This elevated risk occurred primarily among males. The
      adjusted OR for males having more than 10% of their sexual experiences with other
      men was 5.6 (95% CI = 1.4-22.0). A history of other anogenital or endometrial
      cancers increased the risk in women but not men. A history of anal warts,
      syphilis, severe hemorrhoids, physical inactivity, multiple sexual partners who
      smoked, and current smoking were also associated with increased risk.
      CONCLUSIONS: The results of this study suggest that both sexual and non-sexual
      factors are important in the etiology of anal cancer.

PMID- 14682442
TI  - Risk of melanoma in relation to smoking, alcohol intake, and other factors in a
      large occupational cohort.
AB  - OBJECTIVE: To investigate whether smoking, alcohol intake, female hormonal or
      anthropometric factors affect melanoma risk. METHODS: Using Cox proportional
      hazards regression analyses, we analyzed 68,588 white subjects (79% female) from
      the US Radiologic Technologists (USRT) Study who were cancer-free (other than non
      melanoma skin cancer) as of the first of two self-administered questionnaires.
      Follow-up covered 698, 028 person-years, with 207 cases of melanoma. RESULTS: We
      found that melanoma risk was not associated with height, weight or BMI, nor with
      age at menarche, menopausal status, use of hormone replacement therapy, parity,
      age at first birth or oral contraceptive use. Melanoma risk was elevated with
      increasing alcohol use (RR: 2.1: 95% CI: 0.9-4.8, for > 14 drinks/week compared
      to never drinking; (p(trend) = 0.08)). Smoking for long durations compared to
      never smoking was inversely related to melanoma risk (RR: 0.6; 0.3-1.3; > or = 30
      years; p(trend) = 0.03), though risk was not associated with number of packs
      smoked per day. CONCLUSIONS: None of the anthropometric or female
      reproductive/hormonal factors evaluated were related to melanoma risk. It is
      unclear whether the positive association with alcohol intake and inverse
      association with smoking for long duration are causal. The alcohol and smoking
      findings warrant detailed assessment in studies with substantial statistical
      power where potential biases can be more fully evaluated.

PMID- 14682443
TI  - Diet and premalignant lesions of the cervix: evidence of a protective role for
      folate, riboflavin, thiamin, and vitamin B12.
AB  - OBJECTIVE: A case-control study was conducted among a population of multiethnic
      women identified from clinics on Oahu, Hawaii between 1992 and 1996 to explore
      the relationship between diet and cervical dysplasia. METHODS: Two-hundred and
      fourteen women with biopsy-confirmed high and low grade squamous intraepithelial
      lesions of the cervix (SIL) and 271 controls were identified. Exfoliated cervical
      cells were collected for HPV DNA testing. Surveys were administered to assess non
      dietary risk factors and intake of nutrients from over 250 specific food items as
      well as nutritional supplements. RESULTS: Riboflavin and thiamin from food
      sources, vitamin B12 supplements, and total (food and supplements) folate
      displayed inverse, dose-responsive associations with high-grade SIL (HSIL).
      Riboflavin from food sources and total folate also demonstrated inverse, dose
      responsive associations with low-grade SIL (LSIL). The odds ratios for LSIL and
      HSIL were reduced by 50-90% for the highest compared to the lowest levels of
      intake of these nutrients. A number of major food sources of these vitamins,
      including all types of breads, bran cereal, and fruit juice, also demonstrated
      inverse associations with HSIL. There was some evidence that the increased risk
      of HSIL associated with low nutrient intake was most pronounced among drinkers
      and smokers. CONCLUSIONS: This investigation provides evidence that thiamin,
      riboflavin, folate, and vitamin B12 may play a protective role in cervical
      carcinogenesis.

PMID- 14682444
TI  - A critical analysis of reasons for improved survival from invasive cutaneous
      melanoma.
AB  - OBJECTIVE: To determine the extent to which increases in survival from melanoma
      are explained by changes in thickness, level, histological type, site of lesion,
      and sociodemographic characteristics. METHODS: Analyses of changes in survival
      among 9519 South Australians with melanoma reported to the State's population
      based cancer registry during the 1980-2000 diagnostic period, using proportional
      hazards regression to adjust for thickness, level and other characteristics.
      RESULTS: Lower survivals applied for thicker lesions, deeper Clark levels,
      lesions on the trunk and scalp/neck, and for older cases and males. After
      adjusting for these characteristics, the relative risk (95% confidence limits) of
      case fatality for the 1994-2000 diagnostic period was 0.79 (0.63, 0.99), when
      compared with the 1980-1986 baseline. Prior to adjusting, the relative risk for
      these cases was 0.58 (0.47, 0.72). An unexpected finding was a secular change for
      deeper Clark levels within Breslow thickness categories. CONCLUSIONS:
      Approximately half the survival increase was not explained by changes in
      thickness, level, lesion site, and age and sex. Other possible contributors
      warranting further study include changes in ulceration, nodal or more distant
      site involvement, treatment gains and changes in tumour biology. The trend for
      deeper Clark levels within Breslow thickness categories requires independent
      confirmation.

PMID- 14682445
TI  - Family history and colorectal cancer: predictors of risk.
AB  - INTRODUCTION: While the association between family history of colorectal cancer
      in first-degree relatives and risk of developing colon cancer has been well
      defined, the association with rectal cancer is much less clear. The purpose of
      this study is to define rectal cancer risk associated with family history of
      colorectal cancer in first-degree relatives. We also evaluate diet and lifestyle
      factors associated with developing colorectal cancer among participants with a
      positive family history. METHODS: Data were available from two population-based
      case--control studies of colon and rectal cancer. Participants were members of
      the Kaiser Permanente Medical Care Program (KPMCP) or residents of the state of
      Utah. Cases were first primary colon cancer diagnosed between 1991 and 1994 (n =
      1308 cases and 1544 controls) or rectal cancer diagnosed between 1997 and 2001 (n
      = 952 cases and 1205 controls). RESULTS: A family history of colorectal cancer in
      any first-degree relatives slightly increased risk of rectal cancer (OR: 1.37 95%
      CI: 1.02-1.85). Family history of colorectal cancer was associated with the
      greatest risk among those diagnosed at age 50 or younger (OR: 2.09 95% CI: 0.94
      4.65 for rectal tumors; OR: 3.00 95% CI: 0.98-9.20 for distal colon tumors; and
      OR: 7.88 95% CI: 2.62-23.7 for proximal colon tumors). Factors significantly
      associated with cancer risk among those with a family history of colorectal
      cancer, included not having a sigmoidoscopy (OR: 2.81 95% CI: 1.86-4.24): a diet
      not Prudent, i.e. high in fruits, vegetables, whole grains, fish and poultry,
      (OR: 2.79 95% CI: 1.40-5.56); smoking cigarettes (OR: 1.68 95% CI: 1.12-2.53),
      and eating a Western diet, i.e. a diet high in meat, refined grains, high-fat
      foods, and fast foods, (OR: 2.15 95% CI: 1.06-4.35). Physical inactivity was not
      associated with increased cancer risk among those with a positive family history
      of colorectal cancer. SUMMARY: These results confirm observations reported by
      others that a family history of colorectal cancer increases risk of cancer among
      those diagnosed at a younger age. Associations with family history are weakest
      for rectal cancer and strongest for proximal colonic tumors. Since several diet
      and lifestyle factors influence development of cancer among those with a family
      history of the disease, there appears to be practical approaches for individuals
      with a family history of colorectal cancer to reduce their cancer risk.

PMID- 14682446
TI  - Human T-lymphotropic virus type-I infection, survival and cancer risk in
      southwestern Japan: a prospective cohort study.
AB  - OBJECTIVES: This study prospectively evaluated the associations of human T
      lymphotropic virus type-I (HTLV-I) infection with survival and cancer incidence.
      METHODS: The study base comprised 4297 adults (aged 40-69 years in 1993) who had
      either visited the outpatient clinic or who had received annual health check-ups
      at the A Hospital, Nagasaki, Japan, between 1985 and 1992 (HTLV-I seropositivity
      = 24.7%). During the follow-up period (1993-1999 or 2000), 290 deaths and 261
      cases of malignant neoplasms occurred, including ten deaths and six incident
      cases of adult T-cell leukemia/lymphoma (ATL). RESULTS: After adjustment for
      gender, age and other covariates, HTLV-I seropositivity was associated with an
      increased mortality from all-causes excluding ATL (rate ratio, RR = 1.3, 95%
      confidence interval, CI = 1.0-1.7), all non-neoplastic diseases (RR = 1.5, 95% CI
      = 1.0-2.3) and heart diseases. HTLV-I infection was not found to be associated
      with an increased risk of developing total cancers other than ATL (RR = 0.98, 95%
      CI = 0.74-1.3), colorectal cancers, liver cancer or lung cancer, but was
      associated with a reduced risk of gastric cancer (RR = 0.42, 95% CI = 0.17-0.99).
      CONCLUSIONS: HTLV-I infection is associated with increased mortality from all
      causes excluding ATL and all non-neoplastic diseases. HTLV-I carriers may not be
      at increased general cancer risk, but at reduced risk of gastric cancer.

PMID- 14682447
TI  - Effects of alcohol and tobacco on aerodigestive cancer risks: a meta-regression
      analysis.
AB  - OBJECTIVE: Meta-analysis was used to summarize the published evidence on the
      associations between alcohol and tobacco consumption and cancers of the
      oropharynx, pharynx, larynx, and esophagus. The objective was to produce summary
      risk estimates with uniform methods and on uniform exposure scales so that the
      magnitudes of the risks could be compared across tumor sites. METHODS:
      Epidemiologic studies that estimated the effects of alcohol and tobacco
      consumption on the risk of cancers of the upper aero-digestive tract were
      identified from the MEDLINE database, 1966-2001. Alcohol and tobacco data were
      converted into common units (grams/week). For all studies meeting eligibility
      criteria, effect parameters (slopes) were estimated for both exposures. The
      exposure-risk slopes for each study were combined, site by site, using random
      effects meta-regression methods. RESULTS: Fourteen studies met the final
      selection criteria. The carcinogenic effects of alcohol and tobacco were found to
      be multiplicative on the relative risk scale. Tobacco appeared to have a much
      stronger effect on the larynx than on any of the other aerodigestive sites, while
      alcohol's effect was strongest on the pharynx. The weakest association was that
      of alcohol and adenocarcinoma of the esophagus--an order of magnitude weaker than
      that for tobacco and laryngeal cancer. CONCLUSIONS: Meta-analysis was used to
      combine the results from all available studies, providing a comprehensive summary
      of the combined effects of alcohol and tobacco on the upper aerodigestive
      cancers.

PMID- 14682449
TI  - An imported case of Blastomyces dermatitidis infection in Mexico.
AB  - Blastomycosis is an acute or chronic primary infection of the respiratory system,
      endemic in North America (United States of America and Canada), Africa and Asia.
      We report a case in Mexico, in a three years old child who had been born in
      California and lived in Chicago, U.S.A. The patient presented pulmonary symptoms
      prior to development of a skin ulcer. Blastomyces dermatitidis was identified by
      mycological and molecular procedures. The patient was successfully treated with
      amphotericin B, oral ketoconazole and itraconazole.

PMID- 14682450
TI  - Evaluation of the adherence of Candida species to urinary catheters.
AB  - Catheter-associated urinary tract infections (CAUTIs) are the most common kind of
      nosocomial infection. Recent years have seen a significant increase in numbers of
      infections caused by yeasts of the genus Candida. The adherence of a
      microorganism to the host surface is a decisive factor in the success of
      colonization and the pathogenesis of infection. The objective of this work was to
      evaluate the adherence of species of the genus Candida to urinary catheters. In
      vitro adherence to the sections of latex and silicon catheters of Candida
      albicans and Candida parapsilosis were studied. Adherence was measured by
      counting the number of adhering viable cells and the results were expressed as
      Colonies Forming Units per mL. The results demonstrated that the latex catheter
      facilitated adherence more than the silicon catheter (p < 0.01). The adherence of
      the C. albicans was significantly greater than C. parapsilosis on latex, but it
      was similar on silicon.

PMID- 14682448
TI  - Measurement of cellular immunity in human coccidioidomycosis.
AB  - Measurement of cellular immune response in human coccidioidomycosis, a disease of
      the Western Hemisphere caused by the soil-dwelling fungus Coccidioides, began
      more than 75 years ago. Numerous studies have shown that measurement of
      coccidioidal cellular immunity is a useful epidemiologic and clinical tool. The
      first widely used coccidioidal skin-test reagent, coccidioidin, was derived from
      a filtrate of cultured mycelia of Coccidioides by Smith and colleagues in the
      1940's. It remained the standard until the 1970's, when spherulin, obtained from
      the spherule form of the fungus, was found to be more sensitive. Both reagents
      are specific indicators of coccidioidal cellular immunity. Since then, other
      coccidioidal antigens have been identified and in vitro tests of cellular
      immunity have been shown to yield comparable results to skin testing. In vitro
      assays have also begun to open a window on the specific immunologic events of
      coccidioidal cellular immunity. Persistent expression of coccidioidal cellular
      immune response appears to augur an improved clinical outcome. Despite this, a
      study of a coccidioidal vaccine failed to demonstrate efficacy. Current and
      future studies are focused on modulating the coccidioidal immune response in
      vitro and in vivo and on developing an improved vaccine.

PMID- 14682451
TI  - Isolation of Alternaria alternata from an emollient cream: implications for
      public health.
AB  - A specimen of emollient cream, which was observed to be contaminated peripherally
      with a filamentous fungus was examined for the presence of fungi and the
      resulting fungal colonies were examined phenotypically and genotypically.
      Subsequent DNA extraction and PCR amplification of the large internal transcribed
      spacer region [ITS1-5.8S-ITS2] yielded an amplicon of 512 bp. Sequence analysis
      identified this as Alternaria alternata at the 100% homology level with all
      512/512 bases called. This organism has been previously reported as a cause of
      opportunistic infections involving skin and immunocompromised patients. This is
      the first report of an emollient cream as a source of this organism. It
      highlights the need for proper management of such preparations in order to
      minimize the potential spread of fungi to susceptible patient populations.

PMID- 14682452
TI  - Epidemiology of dermatophytoses in an area south of Tehran, Iran.
AB  - Dermatophyte infections have been considered to be a major public health problem
      in many parts of the world. The aim of this study was to identify the etiological
      and epidemiological factors of dermatophyte infections in an area south of
      Tehran. A total of 1254 patients suspected to have dermatophytic lesions were
      examined over a period of three years (1999-2001). Material collected from skin,
      hair, and nails was submitted to direct microscopic examination using KOH,
      cultured in Sabouraud dextrose agar and microscopically examined for colony
      morphology, in order to the identify the 169 dermatophytes isolated. The
      prevalence of dermatophytoses was 13.5% (95% CI: 11.7-15.5%). Their incidence was
      10.6 per 100,000 person-years (95% CI: 8.5-13.2). Epiderophyton floccosum was the
      most frequent dermatophyte isolated (31.4%) followed by Trichophyton rubrum
      (18.3%), T. mentegrophytes (17.2%), T. violaceum (16.6%), Microsporum canis
      (6.5%), T. verrucosum (4.7%) and M. gypseum (4.1%). Epidermophytes floccosum was
      found to be the most common isolated dermatophyte in age groups 20-29 (30.2%).
      Tinea corporis (31.4%) was the most common type of infection, followed by tinea
      cruris (20.7%), tinea manuum (15.4%), tinea capitis (12.4%), tinea pedis (10.6%),
      tinea faciei (7.1%), and tinea unguium (2.4%). The frequency rate of all of the
      types of tinea was higher in males than in females. The anthrophilic species E.
      floccosum was the most common dermatophyte as a causative agent of tinea. The
      most prevalent fungal infection was tinea corporis caused by E. floccosum.

PMID- 14682453
TI  - Blastomyces dermatitidis lysate antigens: antibody detection in serial serum
      specimens from dogs with blastomycosis.
AB  - Yeast phase lysate antigens prepared from different isolates of Blastomyces
      dermatitidis (T-58, dog-Tennessee; T-27, polar bear-Tennessee; ERC-2, dog
      Wisconsin; ER-3, woodpile-Wisconsin) were compared with respect to the detection
      of antibodies (indirect enzyme-linked immunosorbent assay-ELISA, peroxidase
      system) in 126 serial serum specimens (pre-treatment, 30 and 60 days post
      treatment with itraconazole) from 42 dogs with diagnosed blastomycosis. Mean
      absorbance values observed with the four lysate antigens at the three treatment
      intervals ranged from the most reactive to the least reactive as follows: T-58
      (0.270, 0.210, 0.136); T-27 (0.209, 0.156, 0.096); ER-3 (0.189, 0.144, 0.089) and
      ERC-2 (0.158, 0.129, 0.080). Even though variations in reactivity were evidenced,
      the lysates prepared from isolates from various geographical regions and sources
      were all efficacious as antigens for the immunodiagnosis of canine blastomycosis.

PMID- 14682454
TI  - Occurrence of dermatomycoses and in-vitro therapeutic efficacy of three
      antifungal drugs on the growth of Epidermophyton floccosum.
AB  - The occurrence of dermatomycoses and the in-vitro therapeutic efficacy of some
      antifungal agents on dermatomycotic organisms were investigated. Of the 550
      primary school children screened, the incidence was one hundred (18%), 70 were
      males (representing 20% of the males screened) and 30 females (15% of the females
      sampled). The differences between male and female prevalence were insignificant.
      Three species of dermatophytes were isolated and identified. These were
      Microsporum canis, Trichophyton tonsurans and Epidermophyton floccosum. The
      antifungal agents tested on E. floccosum were griseofulvin, terbinafine and
      ketoconazole. They produced different sized zones of inhibition against the
      growth of E. floccosum. Griseofulvin exhibited a 50% inhibition of growth on E.
      floccosum at 63.00 mg/L. Terbinafine on the other hand exhibited varying levels
      of inhibition of growth at varying concentrations, at 0.07 mg/L, terbinafine
      achieved 46% inhibition of growth on E. floccosum. The drug achieved 100%
      inhibition of growth on the isolate at 61.81 mg/L. In the case of ketoconazole,
      50% inhibition of growth was achieved at 100 mg/L while 100% inhibition of growth
      was achieved at 200 mg/L. The antifungal effects of the three drugs were
      confirmed by broth dilution tests where terbinafine was found to be fungistatic
      on the growth of E. floccosum at concentrations ranging from 0.013-1.700 mg/L and
      was fungicidal at concentrations ranging from 0.027-1.700 mg/L. Ketoconazole was
      found to inhibit the growth of E. floccosum at 0.003-1.700 mg/L and was
      fungicidal at concentrations ranging from 0.027-1.700 mg/L. It however did not
      succeed in killing the isolate under the same range of concentrations.
      Griseofulvin exhibited fungistatic effects on the growth of E. floccusum at 0.013
      1.700 mg/L. In conclusion, ketoconazole and griseofulvin were found to be
      fungistatic and not fungicidal while terbinafine was both fungistatic and
      fungicidal on the pathogen. Terbinafine was found to be the most effective drug
      in inhibiting E. floccosum.

PMID- 14682455
TI  - High rate of Microsporum canis feline and canine dermatophytoses in Northeast
      Brazil: epidemiological and diagnostic features.
AB  - Over a one year period (November 2000-December 2001), clinical specimens from 189
      dogs and 38 cats, from the city of Fortaleza, Ceara, Brazil, were examined at the
      Specialized Medical Mycology Center at the Federal University of Ceara to detect
      animals with dermatophytoses. The mycological analyses were conducted by direct
      microscopy and by fungal culture on Sabouraud agar, Sabouraud chloramphenicol
      agar and Mycosel agar. Dermatophytes were isolated from 27 of the 189 (14.3%)
      canine specimens and 14 of the 38 (36.8%) feline specimens. The identified
      dermatophytes were Microsporum canis (95%), M. gypseum (2.5%) and Trichophyton
      mentagrophytes var. mentagrophytes (2.5%). Microsporum canis was the most common
      species isolated (92.6% and 100%, for dogs and cats respectively). The percentage
      of positive direct microscopic examinations of clinical specimens and positive
      cultures was 61%. There was a high proportion of positive cultures from cats less
      than 1 year of age, but in dogs no significant differences were detected. There
      were no significant differences between the sexes. Dermatophytes were more
      frequently isolated in March, April and May, but no significant differences were
      detected in the seasonal distribution of canine and feline dermatophytoses.

PMID- 14682456
TI  - Phaeohyphomycosis caused by Chaetomium globosum in an allogeneic bone marrow
      transplant recipient.
AB  - Bone marrow transplant recipients are highly susceptible to opportunistic fungal
      infections. This is the report, of the first case of a Chaetomium systemic
      infection described in Brazil. A 34 year-old patient with chronic myeloid
      leukemia underwent an allogeneic sibling matched bone marrow transplant. Seven
      months later, he developed systemic infection with enlargement of the axillary
      and cervical lymph nodes. Culture of the aspirates from both lymph nodes yielded
      Chaetomium globosum. The infection was successfully treated with amphotericin B.
      The increasing population of immunosupressed patients requires a careful
      microbiologic investigation for uncommon fungal infections.

PMID- 14682457
TI  - Etiological significance of Candida albicans in otitis externa.
AB  - A study covering 79 patients (42 males, 37 females) of different age groups
      clinically diagnosed as otomycosis were investigated mycologically to elucidate
      the role of Candia albicans, an opportunistic polymorphic yeast, in otitis
      externa. C. albicans was diagnosed as the sole pathogen in two patients (1 male
      and 1 female) aged 18 and 20 years, respectively. The organism was repeatedly
      demonstrated in the aural specimens both by direct microscopy as well as culture
      isolation. Both the patients had unilateral otomycosis and used antibiotic
      solution and removed wax with wooden stick. The topical application of one per
      cent clotrimazole lotion showed good response both clinically as well as
      mycologically. The growing significance of opportunistic fungi emphasizes on
      comprehensive studies to establish the etiologic role in various clinical
      disorders in human and animal medicine.

PMID- 14682458
TI  - Molecular relatedness within the "Ascochyta pinodes-complex".
AB  - The morphological, molecular and pathological characters of 34 isolates
      identified as Ascochyta pinodes, A. phaseolorum, and Phoma medicaginis var.
      pinodella were determined. Initial molecular findings, based on PCR fragment size
      and RFLPs of sections of the mitochondrial genome, the rRNA gene cluster and the
      beta-tubulin gene complex, were further investigated by sequencing of the total
      rRNA ITS regions. Isolates were homogenous for all characteristics determined,
      with the exception of conidial size and septation, and RFLPs of AT rich
      (presumptive mitochondrial) DNA. The results suggest that the isolates represent
      host preferential forms of a single taxon, and this finding is discussed in
      relation to the known teleomorphs and reference material of the species studied.

PMID- 14682459
TI  - Antifungal activity of some deoxyhypusine synthase inhibitors (short
      communication: plant mycology and crop protection).
AB  - Several inhibitors of deoxyhypusine synthase were examined for antifungal
      activity. All compounds, used at concentrations of 1.0 mM or less, reduced
      mycelial growth of the oat leaf stripe pathogen Pyrenophora avenae grown on solid
      media. Four of the compounds completely inhibited fungal growth, 4a doing so at a
      concentration of only 0.61 mM. Inhibition of fungal growth afforded by some of
      the compounds was more marked than was reflected by the radial growth
      measurements.

PMID- 14682460
TI  - Ecology of hymexazol-insensitive Pythium species in field soils.
AB  - Soils from 100 irrigated fields (95 under vegetables, 5 under citrus) in
      different geographical locations in the West Bank (Palestinian Autonomous
      Territory) were surveyed for hymexazol-insensitive (HIS) Pythium species using
      the surface soil dilution plate (SSDP) method with the VP3 medium amended with 50
      mg/L hymexazol (HMI) (VP3H50), over a period of 12 months. HIS Pythium species
      were isolated from 37% of the soils surveyed, with mean population levels ranging
      from 4.3-1422 CFU g(-1) dry weight. Eight HIS Pythium taxa were recovered on the
      VP3H50 medium, the most abundant of which was P. vexans (found in 29% of field
      soils surveyed). Seasonal variations in population levels of HIS Pythium species
      were studied in four fields over a period of 12 months. Significant seasonal
      variations in HIS population levels were detected in the four fields, with the
      highest population levels of HIS Pythium spp. encountered in spring and the
      lowest population levels in winter in three of the fields surveyed. Effects of
      HMI on linear growth and colony morphology of 149 Pythium ssp. isolates were
      examined on CMA amended with HMI at five concentrations. Pythium vexans isolates
      responded differently from those of the other Pythium species. Isolates of this
      important pathogen were more insensitive to HMI at high concentrations than the
      other main species tested. A large proportion of the P. ultimum isolates was
      either insensitive or weakly sensitive to HMI. Furthermore, a few isolates of
      other Pythium species were insensitive to the fungicide at various
      concentrations. The colony morphology of P. vexans isolates was not affected by
      HMI, whereas colonies of the other species showed sparse growth on the HMI
      amended medium relative to the control. The pathogenicity of P. vexans and P.
      ultimum isolates to cucumber seedlings was examined in growth chambers.
      Insensitive isolates of both species were found to be more virulent damping-off
      pathogens than the sensitive isolates. The present study demonstrates that HMI
      can not be used effectively in controlling Pythium spp. in soil inhabited with
      high densities of HIS Pythium spp. pathogens.

PMID- 14682461
TI  - A new species of Protoachlya Upadhyay & Khulbe.
AB  - Protoachlya nainitalensis isolated from mixed oak forest soil (Quercus
      leucotrichophora & Q. floribunda) is described herein. The species is
      characterised by elongated, cylindrical, smooth walled zoosporangia; spherical
      and smooth walled oogonia with androgynous and rarely diclinous branches of
      antheridia. A simplified key of the known Protoachlya species has also been
      established.

PMID- 14682462
TI  - Do trichothecenes reduce viability of circulating blood cells and modify
      haemostasis parameters?
AB  - This manuscript describes the results of experiments conducted using human blood
      cells to determine the ability of T-2 toxin and DON to cause changes in clotting
      time, platelet aggregation, red blood cell haemolysis, RBC glucose content,
      lactate release, glutathione depletion, as well as white blood cell viability. In
      vitro results showed that haemostasis parameters and erythrocytes were not
      affected at concentrations able to induce inhibition of haematopoietic progenitor
      proliferation. In the presence of 10(-8) M and 10(-6) M T-2, the leucocyte number
      decreased at 24 h by 30% and 50% respectively. A 50% decrease in leucocyte number
      was observed for 10(-5) M DON. Results were compared with haematopoietic
      progenitor sensitivities. Due to the differences in sensitivities between mature
      blood cells and haematopoietic progenitors, haematological problems associated
      with trichothecene intoxication could be attributed to haematopoiesis inhibition.

PMID- 14682464
TI  - Identification of virulent isolates of the entomopathogenic fungus Nomuraea
      rileyi (F) Samson for the management of Helicoverpa armigera and Spodoptera
      litura (identification of virulent isolates of N. rileyi).
AB  - Eleven geographical isolates of the entomopathogenic fungus Nomuraea rileyi
      (Farlow) Samson of Helicoverpa armigera (Hubner)/Spodoptera litura (Fabricius)
      origin were studied for efficacy against the two host insects. Laboratory
      bioassays at a concentration of 2 x 10(8) conidia ml(-1) indicated that N. rileyi
      isolates of S. litura origin were better in terms of time taken for mycosis and
      mortality in both the test larvae: S. litura (77-80% mortality in 7 days) and H.
      armigera (79-85% in 8 days). Among the isolates of S. litura origin, geographical
      isolates from Hyderabad and Karimnagar were superior in terms of high percent
      kill as well as 100% germination of conidia within 48 h. Fastest germination was
      observed with Karimnagar isolate followed by Hyderabad isolate. Conidial yield
      was highest on barley-carrot extract-yeast extract medium. However in terms of
      material cost, barley-yeast extract medium was the lowest. The Karimnagar isolate
      of S. litura origin gave the highest conidial yield on barley-yeast extract
      medium. Chitinolytic enzyme profiles of different isolates revealed polymorphism
      in all the isolates from S. litura origin. Overall among the parameters studied
      the best traits were found in the Karimnagar isolate of S. litura origin.

PMID- 14682463
TI  - Fumonisin and beauvericin induce apoptosis in turkey peripheral blood
      lymphocytes.
AB  - Fumonisins, a family of mycotoxins produced by Fusarium verticillioides (synonym
      Fusarium moniliforme Sheldon) and F. proliferatum, have been associated with
      various deleterious effects in different animal species. Serological,
      hematological and pathological effects and mortality have previously been
      observed in broiler chicks fed F. proliferatum culture material containing known
      concentrations of fumonisin, moniliformin and beauvericin. Turkey peripheral
      blood lymphocytes were exposed in vitro for 72 hours to fumonisin B1 (FB1),
      fumonisin B2 (FB2), hydrolyzed fumonisin B1 (HFB1), moniliformin and
      tricarballylic acid (TCA) (0.01-25 microg/ml). A decrease in cell proliferation,
      as determined by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide] bioassay, occurred in the order: FB2 > FB1 > HFB1, with IC50 = 0.6
      microM, 1 microM and 10 microM, respectively. Internucleosomal DNA fragmentation
      and morphological features characteristic of apoptosis were observed following
      exposure to fumonisin B1 and beauvericin; cytoplasmic condensation and membrane
      blebbing were seen by light microscopy. Tricarballylic acid and moniliformin did
      not interfere with cell proliferation. Results suggested that fumonisin B1 and
      beauvericin may affect immune functions by suppressing proliferation and inducing
      apoptosis of lymphocytes.

PMID- 14682465
TI  - Pathogenicity of Metarhizium anisopliae (Metsch.) Sorokin and Beauveria bassiana
      (Balsamo) Vuillemin, to three adult fruit fly species: Ceratitis capitata
      (Weidemann), C. rosa var. fasciventris Karsch and C. cosyra (Walker) (Diptera
      :Tephritidae).
AB  - The pathogenicity of two isolates of Beauveria bassiana and 12 of Metarhizium
      anisopliae towards adult fruit flies, Ceratitis capitata and Ceratitis rosa var.
      fasciventris was tested in the laboratory. Fruit flies were exposed to dry
      conidia evenly spread on velvet material covering the inner side of a cylindrical
      plastic tube. All isolates tested were pathogenic to both species of fruit flies.
      Mortality ranged from 7 to 100% in C. capitata and from 11.4 to 100% in C. rosa
      var. fasciventris at 4 days post-inoculation. Six isolates, M. anisopliae ICIPE
      18, 20, 32, 40, 41 and 62, were highly pathogenic to both C. capitata and C. rosa
      var. fasciventris. The LT90 values of the most pathogenic isolates ranged between
      3-4 days in both insects. Because of the difficulties in rearing C. cosyra, only
      the isolates that were highly pathogenic to both C. rosa var. fasciventris and C.
      capitata were tested against adult C. cosyra. They caused mortality of between 72
      78% at 4 days post-inoculation. The LT90 values in all the isolates did not
      exceed 4 days. One of the most pathogenic isolates, M. anisopliae ICIPE 20, was
      evaluated against C. capitata and C. rosa var. fasciventris in cage experiments
      using three autoinoculators (maize cob, cheesecloth and Petri dish) in an
      autoinoculative device consisting of plastic mineral bottle. Mortality of between
      70-93% was observed in flies of both species that were captured from the cages
      and held under laboratory conditions. These results indicate the possibility of
      fruit fly suppression with entomopathogenic fungi using an autoinoculative
      device.

PMID- 14682466
TI  - A novel nonsense mutation in the Cyp11B1 gene from a subject with the steroid
      11beta-hydroxylase form of congenital adrenal hyperplasia.
AB  - 11beta-Hydroxylase deficiency (11beta-OHD) inherited in an autosomal recessive
      manner accounts for about 5-8% of congenital adrenal hyperplasia (CAH). In order
      to clarify the underlying mechanism causing 11beta-OHD, we have done the
      molecular genetic analysis on the CYP11B1 gene in a patient diagnosed as 11beta
      OHD. The nucleotide sequence of the patient's CYP11B1 revealed a novel nonsense
      mutation that converts codon 265 CAG (glutamine) to TAG (stop) of exon 4.
      Restriction fragment length polymorphism (RFLP) data showed that the patient was
      homozygous for the mutation. The above results confirm that the patient suffers
      from complete loss of the final step in cortisol biosynthesis pathway because of
      the nonsense mutation.

PMID- 14682467
TI  - A comparative study on body figure and serum lipid profile between aboriginal and
      Chinese elementary schoolchildren in mid-Taiwan.
AB  - The aim of this study was to compare the body figure and serum lipid profiles of
      aboriginal students living in rural side in Nantou and Chinese students living in
      Taichung City. METHODS: Body figure and blood lipid profile was examined in
      elementary school fifth grade aboriginal students in Nantou and Chinese students
      in Taichung City, aged 10-year-10-month old to 11-year-6-month old. RESULTS: In
      girls, aboriginal students in Nantou have higher body mass index (BMI) (20.7 vs.
      17.83 kg/m2, p < 0.01) and percentage of overweight (46.43% vs. 21.28%, p < 0.05)
      than Chinese students in Taichung City. However, Chinese girls have higher levels
      of total cholesterol (175.17 vs. 150.36 mg/dL, p < 0.01), low-density lipoprotein
      cholesterol (104.31 vs. 92.78 mg/dL, p < 0.05), and high-density lipoprotein
      cholesterol (54.96 vs. 43.49 mg/dL, p < 0.01) than aboriginal girls. In boys,
      body height of Chinese students in Taichung city is significantly higher (144.37
      vs. 139.71 cm, p < 0.01) than aboriginal students but other body figure and blood
      lipid profile have no significant difference. CONCLUSIONS: Our results suggest
      that in Taiwan BMI and blood lipid profile differ in female children by race and
      geographical location but this is not so for male children.

PMID- 14682468
TI  - Relationships existing between the serum cytokine levels and bone mineral density
      in women in the premenopausal period affected by Graves' disease with subclinical
      hyperthyroidism.
AB  - We examined the relationships existing between serum cytokine levels and bone
      mineral density (BMD) in women of premenopausal age affected by Graves' disease
      with subclinical hyperthyroidism. The study population consisted of 21 women with
      untreated hyperthyroid Graves' disease (group H) (age, 36 +/- 2 years), eight
      women with untreated subclinical hyperthyroid status (group SH) (age, 33 +/- 5
      years) and 10 healthy women (group N) (age, 35 +/- 3 years). The following
      measurements were made in all patients: free T4 (fT4), free T3 (fT3), thyroid
      stimulating hormone (TSH), TSH receptor antibody (TRab), anti-thyroid peroxidase
      antibody (anti-TPO), anti-thyroglobulin antibody (anti-Tg), interleukin-2
      receptor (IL-2r), interleukin-4 (IL-4), interleukin-8 (IL-8) and interleukin-13
      (IL-13). IL-2r and IL-8 levels significantly increased in group H compared with
      group SH (p < 0.01 and p = 0.05, respectively) and group N (p < 0.001 and p =
      0.02, respectively). IL-4 and IL-13 levels tended to be lower in groups H and SH
      compared with group N, although this difference did not reach statistical
      significance. Bone mineral density was significantly reduced in only two areas of
      the femur in group H compared with group N. There was no difference in BMD
      between groups SH and N. There was no correlation between thyroid hormones, serum
      cytokine levels and BMD in either group. In conclusion, these results suggest
      that there were no relationships existing between the serum level of these
      cytokines and BMD in women of premenopausal age affected by Graves' disease with
      subclinical hyperthyroidism.

PMID- 14682469
TI  - In vitro modulation of steroidogenesis and gene expression by melatonin: a study
      with porcine antral follicles.
AB  - The effects of melatonin on steroidogenesis and gene expression of CYP 11A, CYP
      17, and CYP 19 were investigated using a porcine antral follicle culture model.
      Follicles were cultured with melatonin at doses of 10, 50, and 100 ng/mL in the
      presence and absence of an optimum dose of luteinizing hormone (LH) (100 ng/mL)
      for a period of 30 hours. It was found that melatonin stimulated progesterone
      production both in the presence and absence of LH. Androstenedione production was
      stimulated by melatonin at the highest dose of 100 ng/mL but melatonin had an
      inhibitory effect in the presence of LH. Estradiol production was not affected by
      melatonin alone, while in the presence of LH it showed a bimodal effect.
      Expression of genes for steroidogenic enzymes specific for the production of
      progesterone, androstenedione and estradiol (CYP 11A, CYP 17, and CYP 19,
      respectively) were also analyzed in the theca of follicles cultured with and
      without LH. Results showed an inhibition of CYP 11A and CYP 17 expression both in
      the presence and absence of LH. However, the expression of CYP 19 was not
      affected. Our results indicate that melatonin modulates ovarian theca cell
      steroidogenesis at the molecular level and this modulation may be mediated by its
      effects on the transcriptional activity of the steroidogenic enzymes.

PMID- 14682470
TI  - Cortisol metabolism and visceral obesity: role of 11beta-hydroxysteroid
      dehydrogenase type I enzyme and reduced co-factor NADPH.
AB  - Several factors including genetic and environmental play a role in the
      development of obesity and the metabolic syndrome. The transgenic mouse
      overexpressing 11beta-hydroxysteroid dehydrogenase (11beta-HSD) develops visceral
      obesity. However, it remains unclear how a ubiquitously expressed 11beta-HSD1
      enzyme affects adipose tissue so much that it would lead to obesity. In this
      commentary we explore the possibility that increased intracellular availability
      of reduced co-factor, NADPH, could exacerbate the enzymatic activity.

PMID- 14682471
TI  - Effects of alpha-tocopherol on diabetes-induced alterations of synaptic
      transmission and contractile features in murine dorsiflexor muscle.
AB  - Diabetes mellitus affects skeletal muscle and free radicals may be implicated in
      the manifestation of diabetes complications. The present study investigated
      effects of alpha-tocopherol on diabetic dorsiflexor muscle via recording resting
      membrane potentials (RMPs), endplate potentials (EPPs), miniature endplate
      potentials (MEPPs) and isometric twitch tensions. Forty mice were divided
      randomly into two groups (n = 20). One group served as control and the other was
      injected once with streptozotocin (STZ) solution (60 mg/kg, i.p) to induce
      diabetes. The animals were then divided further into two subgroups (n = 10).
      Alpha-tocopherol (100 mg/kg, i.p) was administered daily to one control and one
      diabetic group for 3 weeks prior to recording day. Experiments were conducted 4
      weeks following diabetes induction. Isometric twitch tension was measured in
      anaesthetized mice (2 mg/g urethane, i.p) via a transducer connected to a
      computer system. Resting membrane potentials and MEPPs were measured by utilizing
      the intracellular recording method. Compared to control, diabetic mice showed
      reduced twitch tension (4.4 +/- 0.4 g control vs. 2.5 +/- 0.3 g diabetic) and
      demonstrated delayed half time of decay. Diabetic flexor muscle also displayed
      significant reduction in MEPPs frequencies with no changes in RMPs. Alpha
      tocopherol reversed tension reduction in diabetic mice (from 2.5 +/- 0.3 to 3.8
      +/- 0.4 g), impacted delayed half time of decay and reversed reduction in MEPPs
      frequencies. Alpha-tocopherol exerts a protective role against diabetes-induced
      peripheral muscle dysfunction. This effect is probably mediated via a free
      radical scavenging mechanism or modification of Ca2+ homeostasis.

PMID- 14682472
TI  - The morpho-anatomy and histology of the pineal complex in a major Indian carp,
      Catla catla: identification of the pineal photoreceptor cells and their
      responsiveness to constant light and constant darkness during different phases of
      the annual reproductive cycle.
AB  - In contrast to mammals in which the pineal gland is a discrete structure situated
      dorsally in the brain, the "pineal gland" in teleost fishes is composed of a
      number of separate but connected constituent parts, collectively described as the
      "pineal complex." In this paper, we have described the pineal complex in a common
      Indian carp, Catla catla, which exhibits an annual reproductive cycle. Attempts
      have been made to (a) provide an in-depth description of the structure of the
      pineal complex; and (b) identify the photoreceptor cells of the pineal, by
      exposing the animals to constant light (LL) and constant darkness (DD).
      Furthermore, we examined any possible influence of the reproductive status of the
      fish on the responsiveness of the pineal photoreceptor cells in C. catla
      following exposure to LL and DD. To this end, a total of four experiments were
      carried out during the four different phases of the annual reproductive cycle
      that is characteristic of this species. Each of these four experiments was
      carried out for a period of 30 days after which the fishes were sacrificed,
      different parts of the pineal complex were dissected out, and processed for
      histological and karyometric studies. Our results showed that the pineal complex
      in this species is composed of three separate but connected parts, (a) an end
      vesicle (EV); (b) a dorsal sac (DS); and (c) a long and thin pineal stalk (PS)
      that attaches the EV to the DS. Detailed karyometric and histo-morphologic
      studies following exposure of the animals to DD and LL showed that constant
      darkness led to a stimulatory effect on the pineal photoreceptor cells of the EV
      as evident from a significant increase in the nuclear diameter. In contrast, the
      nuclear diameter of the photoreceptor cells in animals subjected to constant
      light showed a significant reduction. Furthermore, the observed cellular changes
      in the EV of fish exposed either to LL or DD were independent of the stage of the
      gonadal cycle. The apparent lack of any cellular responses either in the PS, or
      in the DS, following exposure to LL and DD, suggests that in C. catla the
      photoreceptor cells are located only within the epithelial lining of the EV and
      that these cells respond in a manner similar to mammalian pinealocytes when
      subjected to comparable photoperiod-induced experimental conditions.

PMID- 14682473
TI  - Effects of melatonin on skeletal muscle of rats with experimental
      hyperthyroidism.
AB  - The aim of this study was to investigate structural changes that occurred in the
      skeletal muscle of rats with experimental hyperthyroidism and the effect of
      melatonin on these changes. Groups of animals were designated as controls, 3,3',5
      triiodothyronine (T3) injected and T3 + melatonin injected group. At the end of
      the study the tissue specimens were harvested and their structure examined. In
      the skeletal muscle of T3 injected rats a decrease was observed in muscle fiber
      diameter, splitting of fiber, collections of adipose tissue in perimysium, and
      gathering of nuclei in central compared to the control. Electron microscopic
      examination showed that mitochondria were dilated and the I band was less clear.
      In the T3 + melatonin injected group, the structure of fibers was similar to
      control. In conclusion, this study showed that T3 injection caused structural
      changes in the skeletal muscle and that melatonin had a positive effect on these
      changes.

PMID- 14682474
TI  - Dominant negative protein kinase Cbeta improves 1alpha, 25-dihydroxy vitamin D3
      induced insulin resistance.
AB  - 1alpha,25-Dihydroxy vitamin D3 (1,25D3) activates conventional PKC and may
      subsequently lead to insulin resistance. Previous studies from our laboratory
      have shown that pretreatment with 10 nM-10 microM 1,25D3 dose-responsively
      suppressed insulin-induced glucose. To assess PKC(beta)-mediated inhibition of
      insulin-induced glucose uptake in rat adipocytes, we preincubated with Go6976 and
      LY379196, conventional PKC inhibitors, and found they abolished the 1,25D3
      mediated inhibitory effect on insulin-induced 2-deoxyglucose (DOG) uptake.
      Moreover, the inhibitory effect of 1,25D3 on insulin-induced DOG uptake was
      abrogated in adipocytes overexpressed with dominant negative PKC(beta), but not
      in those overexpressed with wild type PKC(beta). These results suggest that
      1,25D3 reduces insulin-induced glucose uptake via activation of PKC(beta) in rat
      adipocytes.

PMID- 14682475
TI  - Expression of c-erbB-2 oncoprotein in different types of thyroid tumors: an
      immunohistochemical study.
AB  - AIMS: c-erbB-2 expression has been found to be an important prognostic parameter
      in various types of tumors, but the role played by this oncoprotein in thyroid
      tumors is still controversial. This study is designed to investigate c-erbB-2
      expression in different types of thyroid tumors. METHODS: c-erbB-2 protein over
      expression was studied immunohistochemically (IHC) in 68 paraffin-embedded
      thyroid tumors (12 follicular adenomas, 20 papillary carcinomas, 20 follicular
      carcinomas, eight medullary carcinomas, eight anaplastic carcinomas), diagnosed
      at the Pathology Department of Cukurova University. RESULTS: No expression of c
      erbB-2 was found in anaplastic carcinomas, but 50% of the papillary carcinomas
      showed a cytoplasmic staining pattern and 45% had a mixed staining pattern
      (cytoplasmic and membranous patterns). Eight (40%) of the 20 follicular
      carcinomas showed a mixed cytoplasmic/membranous staining pattern and three (15%)
      showed only cytoplasmic reactivity. Cytoplasmic immunoreactivity was detectable
      for c-erbB-2 in six out of eight (75%) medullary carcinomas. Finally, seven cases
      of 12 (58%) follicular adenomas showed cytoplasmic staining. CONCLUSIONS:
      Investigation of the exact role of c-erbB-2 in thyroid tumors requires further
      studies, and the different patterns of immunostaining may be helpful for
      determination of prognosis as is the case in breast carcinoma.

PMID- 14682476
TI  - Pinealectomy and zinc deficiency have opposite effects on thyroid hormones in
      rats.
AB  - The present study was conducted to investigate how pinealectomy and zinc
      deficiency separately or in combination affected thyroid hormones in rats. The
      study was carried out on 40 Sprague-Dawley male rats. The rats were equally
      allocated to four groups: Group 1 (control group), Group 2 (zinc-deficient
      group), Group 3 (pinealectomized group) and Group 4 (pinealectomized and zinc
      deficient group). At the end of a 4-week study period, the rats were decapitated
      and blood samples were taken. The samples were examined in terms of plasma zinc,
      melatonin, free and total T3, T4, and TSH. It was found that free T3 and T4
      levels in the pinealectomized group (Group 3) were higher than all others (p <
      0.01) while free T3, T4, and TSH levels in the zinc-deficient group (Group 2)
      were lower than all others (p < 0.01). Free T3 and T4 levels in the
      pinealectomized zinc-deficient group (Group 4) were lower than those in Groups 1
      and 3 and higher than those in Group 2 (p < 0.01). The findings obtained at the
      end of the study period show that pinealectomy has a stimulating and zinc
      deficiency has a suppressing effect on thyroid hormones and that the suppressing
      effect caused by zinc deficiency is partially balanced by pinealectomy.

PMID- 14682478
TI  - Three types of skills for effective forensic psychological assessments.
AB  - This article examines three types of skills required for effective assessments in
      the forensic arena. Forensic psychology is the application of scientific
      psychology to the resolution of legal conflicts. The first skill is knowledge of
      the legal issues to be addressed. Examples of such issues are criminal
      responsibility, legal competencies, and linking mental states to legal issues in
      question. The second set of skills comprises those skills often required by the
      demands of the legal system--specifically, gathering complete information about
      the case at hand, striving for neutrality, reconstructing the past, and
      predicting the future. The last set of skills includes practical ones required
      during the process of litigation--that is, supporting the retaining attorney's
      overall strategy, addressing the testimony to the appropriate audience, and
      deferring to the prerogative of the fact finder.

PMID- 14682477
TI  - Effects of progesterone and 18-methyl levonorgestrel on osteoblastic cells.
AB  - OBJECTIVE: To study the effects of progesterone (P) and 18-methyl levonorgestrel
      (LNG) on the expression of P receptors (PRA and PRB), c-fos, c-jun, and
      osteocalcin in the human osteosarcoma cell line MG-63 and human normal
      osteoblasts in order to understand the mechanism of progestin action on the
      proliferation and differentiation of osteoblasts. METHODS: Cell proliferation was
      tested by MTT assay. The expression of PR, c-fos, c-jun, and osteocalcin was
      measured by semi-quantitative RT-PCR, Western immunoblot or immunocytochemistry.
      RESULTS: Progesterone and LNG (10(-10)-10(-6)M) stimulated cell proliferation in
      a dose-dependent manner. Progesterone and LNG did not affect the expression of
      PRA and PRB mRNA and protein, but c-fos and c-jun mRNA and protein were
      upregulated in a dose-dependent manner. The expression of osteocalcin mRNA was
      also increased in human osteoblasts in a dose and time-dependent manner with
      greater effects of LNG than P, while the expression of osteocalcin mRNA in MG-63
      cells was not changed by P or LNG. CONCLUSION: Progesterone and LNG promote
      osteocalcin gene transcription by stimulating the expression of c-fos and c-jun,
      and result in osteoblast proliferation and differentiation.

PMID- 14682479
TI  - Principles of forensic mental health assessment: implications for
      neuropsychological assessment in forensic contexts.
AB  - Forensic mental health assessment (FMHA) is a form of evaluation performed by a
      mental health professional to provide relevant clinical and scientific data to a
      legal decision maker or the litigants involved in civil or criminal proceedings.
      Such FMHA evaluations can be further specialized when the clinical and scientific
      data are primarily neuropsychological. This paper provides an adaptation of 29
      recently derived principles of FMHA (Heilbrun, 2001) that have been described in
      two forms: general guidelines for application in FMHA, and guidelines for
      application to neuropsychological assessment in forensic contexts. Each principle
      is described, and the general guideline is compared with the highly specialized
      neuropsychological guideline. In this way, the applicability of such FMHA
      principles to forensic neuropsychological assessment is described.

PMID- 14682480
TI  - Assessing dimensions of competency to stand trial: construct validation of the
      ECST-R.
AB  - Four decades of forensic research have left unanswered a fundamental issue
      regarding the best conceptualization of competency to stand trial vis-a-vis the
      Dusky standard. The current study investigated three competing models (discrete
      abilities, domains, and cognitive complexity) on combined data (N = 411) from six
      forensic and correctional samples. Using the Evaluation of Competency to Stand
      Trial-Revised (ECST-R), items representative of the Dusky prongs were used to
      test the three models via maximum-likelihood confirmatory factor analyses (CFA).
      Of the three, only the discrete abilities model evidenced a good fit, indicating
      that competency to stand trial should consider separately each defendant's
      factual understanding of the proceedings, rational understanding of the
      proceedings, and ability to consult with counsel. ECST-R competency scales, based
      on the current CFA, have excellent alphas (.83 to .89) and interrater
      reliabilities (.97 to .98).

PMID- 14682481
TI  - Legal and psychological implications in the assessment of sexual consent in the
      cognitively impaired population.
AB  - The question of competency to consent to sexual activity in the cognitively
      impaired population continues to be a difficult assessment issue. Problems center
      on inconsistent legal and clinical criteria, current inadequate methods of
      psychological assessment, and the need to promote basic human rights, while
      protecting people from harm. The purpose of this study was twofold. First, the
      problems inherent in the psychological assessment of competency to consent to
      sexual activity are discussed with an emphasis on problems defining consent
      competency. Second, the utility of a neuropsychological test battery in assisting
      with the assessment of the ability to consent to sexual activity was examined.
      Findings indicated that executive measures of neuropsychological assessment were
      primarily associated with competency to consent to sexual activity. It is
      important that these neuropsychological measures were more accurate in
      categorizing competent and noncompetent individuals than methods currently in
      use. This suggests that sexual consent assessments in the forensic arena should
      include neuropsychological testing and that current methods are insufficient.

PMID- 14682482
TI  - Juvenile offenders' Miranda rights comprehension and self-reported likelihood of
      offering false confessions.
AB  - This study examined whether age, IQ, and history of special education predicted
      Miranda rights comprehension and the self-reported tendency to falsely confess to
      a crime among 55 delinquent boys. The Miranda Rights Comprehension Instruments
      II, a revised version of Grisso's Instruments for Assessing Understanding and
      Appreciation of Miranda Rights, were developed for this study and are described
      in detail in this article. Results revealed that age, IQ, and special education
      were related to comprehension of Miranda rights. When Miranda comprehension, age,
      and IQ were simultaneously tested as predictor variables of the self-reported
      likelihood of false confessions, only age served as an independent predictor.
      Research and policy implications of this study are presented, and recommendations
      for use of the original and revised instruments are reviewed.

PMID- 14682483
TI  - Use of the TOMM in a criminal court forensic assessment setting.
AB  - Use of the Test of Memory Malingering (TOMM) in a criminal court forensic
      assessment setting was examined. Results indicated that those initially suspected
      of cognitive malingering and, thus, administered the TOMM, differed from others
      in this setting in ways that are consistent with descriptions of suspected
      cognitive malingerers in the existing literature. These defendants' TOMM scores
      were also consistent with those reported in samples characterized by relatively
      high base rates of cognitive malingering. Defendants whose TOMM scores met the
      recommended criteria for detecting malingering (n = 29) were more likely to
      report a previous head injury, to be viewed as only marginally cooperative or
      uncooperative during the course of the evaluation, and to be diagnosed with
      antisocial personality disorder than those who did not generate suspicious TOMM
      scores.

PMID- 14682484
TI  - An MMPI-2 scale to detect malingered depression (Md scale).
AB  - A specialized Minnesota Multiphasic Personality Inventory-2 (MMPI-2) validity
      scale was constructed to detect individuals who are knowledgeable about either
      depression or MMPI-2 detection strategies and who subsequently attempt to
      malinger depressive symptoms on the MMPI-2. The Malingered Depression (Md) scale
      consists of 32 items that discriminated college students who feigned depression
      from those who were genuinely depressed. Further information about the
      incremental validity and the utility of the Md scale was obtained in a cross
      validation study with additional college students who feigned depression and a
      sample of students with clinically significant depressive symptoms. The results
      indicate that the Md scale possesses promising value in detecting malingered
      symptoms of depression.

PMID- 14682485
TI  - Correlates of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2)
      Personality Psychopathology Five (PSY-5) scales in a forensic assessment setting.
AB  - Empirical correlates of the Minnesota Multiphasic Personality Inventory-2 (MMPI
      2) Personality Psychopathology Five (PSY-5) scales in a forensic assessment
      setting were identified. Archival extratest data, including demographics,
      psychosocial history, criminal behavior history, and current mental status and
      psychodiagnosis, were extracted from the case files of 593 men and women referred
      to a forensic assessment clinic for criminal court-ordered evaluations. Zero
      order and multiple correlations were calculated between the MMPI-2 PSY-5 scales
      and relevant criterion variables. Findings indicated that the PSY-5 scales'
      empirical correlates in a forensic setting are similar to and consistent with
      those found in general mental health settings. Linear combinations of MMPI-2 PSY
      5 Scale scores accounted for moderate proportions of variance in the collateral
      indicators.

PMID- 14682486
TI  - MMPI-A characteristics of male adolescents in juvenile justice and clinical
      treatment settings.
AB  - The current study investigates the extent to which the Minnesota Multiphasic
      Personality Inventory-Adolescent (MMPI-A) profiles of 196 male adolescents
      evaluated in a South Carolina detention center could be successfully
      discriminated from the protocols of 200 male adolescent psychiatric inpatients in
      three states and 151 dually diagnosed male adolescents. Results showed
      significant differences in mean T-score values among these three groups of
      adolescents across a variety of MMPI-A scales and subscales. Results from
      discriminant function analyses indicate that treatment setting can be predicted
      effectively from MMPI-A profiles. Beyond the MMPI-A profile differences
      established for adolescents in these groups, the similarities of adolescents were
      also noted, particularly in terms of the frequent occurrence of Within-Normal
      Limits profiles for adolescents in all groups. Potential directions for future
      research with the MMPI-A are presented.

PMID- 14682487
TI  - The utility of psychological testing in assessing emotional damages in personal
      injury litigation.
AB  - Psychological testing and assessment instruments frequently play a small but
      important role when psychologists assist the courts as emotional damage experts
      in personal injury matters. However, examiners frequently, if sometimes
      inadvertently, mislead the court with test interpretations that are based on
      clinical rather than forensic populations and that fail to appreciate the lack of
      robustness of clinical measures in this forensic context. Whereas published
      computerized interpretations repeatedly remind experts that personality test
      results should only be used as a method to generate hypotheses about the examinee
      that are to be subjected to further investigation and consideration, experts all
      too often inform the courts of test interpretations as if the test results were
      measures of clinical constructs rather than plaintiffs' self-reports of symptoms.

PMID- 14682488
TI  - Emotional risk factors and postconcussional disorder.
AB  - Emotional risk factors were examined in 129 litigant and nonlitigant patients
      diagnosed with Postconcussional Disorder (PCD) following Mild Traumatic Brain
      Injury (MTBI). According to Millon Clinical Multiaxial Inventory (MCMI) criteria,
      four subgroups emerged: (a) 14.7% met criteria for an Axis I disorder, (b) 24.8%
      for an Axis II disorder, (c) 24.0% for bout Axis I and II disorders, and (d)
      36.4% fell below threshold for psychopathology. Thus, 63.5% endorsed emotional
      pathology. Of the four groups, those with both Axis I and II psychopathology
      presented the greatest number of emotional complaints in a clinical interview and
      manifested the lowest neurocognitive test scores. Motor skills, verbal abilities,
      memory functioning, and IQ were primarily affected. With the exception of post
      morbid emotional complaints, no significant differences were identified between
      litigants and nonlitigants. Our analysis suggests that the combination of both
      Axis I and II psychopathology is associated with greater impairment following
      MTBI.

PMID- 14682489
TI  - Holistic thinking is not the whole story: alternative or adjunct approaches for
      increasing the accuracy of legal evaluations.
AB  - There are a number of very helpful, but often underutilized, principles and
      procedures that can augment decision making in clinical and legal settings.
      Psychologists often restrict their range of decision-making strategies and
      options--at the cost of maximizing diagnostic and predictive accuracy--in part as
      the result of "ontological-epistemological one-worldedness" (O-E O-W). However,
      no philosophical, logical, or scientific necessity demands strict consistency
      between views regarding the nature of psychological phenomena and views about how
      to best assess or learn about those phenomena. Relaxing this unnecessary and
      largely psychologically-based O-E O-W may promote greater comfort with and
      utilization of the methods that are discussed in this article for increasing
      judgmental accuracy.

PMID- 14682490
TI  - The quest for surrogate markers of angiogenesis: a paradigm for translational
      research in tumor angiogenesis and anti-angiogenesis trials.
AB  - Inhibition of tumor angiogenesis suppresses tumor growth and metastatic spreading
      in many experimental models, suggesting that anti-angiogenic drugs may be used to
      treat human cancer. During the past decade more than eighty molecules that showed
      anti-angiogenic activity in preclinical studies were tested in clinical cancer
      trials, but most of them failed to demonstrate any measurable anti-tumor activity
      and none have been approved for clinical use. Recent results stemming from trials
      with anti-VEGF antibodies, used alone or in combination with chemotherapy,
      suggest that systemic anti-angiogenic therapy may indeed have a measurable impact
      on cancer progression and patient survival. From the clinical studies it became
      nevertheless clear that the classical endpoints used in anti-cancer trials do not
      bring sufficient discriminative power to monitor the effects of anti-angiogenic
      drugs. It is therefore necessary to identify and validate molecular, cellular and
      functional surrogate markers of angiogenesis to monitor activity and efficacy of
      anti-angiogenic drugs in patients. Availability of such markers will be
      instrumental to re-evaluate the role of tumor angiogenesis in human cancer, to
      identify new molecular targets and drugs, and to improve planning, monitoring and
      interpretation of future studies. Future anti-angiogenesis trials integrating
      biological endpoints and surrogate markers or angiogenesis will require close
      collaboration between clinical investigators and laboratory-based researchers.

PMID- 14682491
TI  - Naturally arising CD25+CD4+ regulatory T cells in maintaining immunologic self
      tolerance and preventing autoimmune disease.
AB  - A large body of evidence indicates that T cell-mediated dominant suppression of
      self-reactive T cells is indispensable for maintaining immunologic
      unresponsiveness to self-constituents (i.e., self-tolerance) and preventing
      autoimmune disease. CD25+CD4+ regulatory T cells naturally present in normal
      animals, in particular, engage in this function, as their reduction or functional
      abnormality leads to the development of autoimmune disease in otherwise normal
      animals. They are at least in part produced by the normal thymus as a
      functionally mature and distinct subpopulation of T cells. Recent studies have
      demonstrated that CD25+CD4+ regulatory T cells control not only autoimmune
      reactions but also other immune responses, including tumor immunity,
      transplantation tolerance and microbial infection. Thus, this unique population
      of regulatory T cells can be exploited to control pathological as well as
      physiological immune responses.

PMID- 14682492
TI  - A conceptual view on glucocorticoid-lnduced apoptosis, cell cycle arrest and
      glucocorticoid resistance in lymphoblastic leukemia.
AB  - Glucocorticoids (GC) control cell cycle progression and induce apoptosis in cells
      of the lymphoid lineage. Physiologically, these phenomena have been implicated in
      regulating immune functions and repertoire generation. Clinically, they form the
      basis of inclusion of GC in essentially all chemotherapy protocols for lymphoid
      malignancies. In spite of their significance, the molecular mechanisms underlying
      the anti-leukemic GC effects and the clinically important phenomenon of GC
      resistance are still unknown. This review summarizes recent findings related to
      GC-induced apoptosis, cell cycle arrest, and GC resistance with particular
      emphasis on acute lymphoblastic leukemia (ALL). We hypothesize that under
      conditions of physiological Bcl-2 expression, GC might induce classical
      programmed cell death by directly perturbing the Bcl-2 rheostat. In the presence
      of anti-apoptotic Bcl-2 proteins, cell death might result from accumulating
      catabolic and/or other detrimental GC effects driven by, and critically dependent
      on, GC receptor (GR) autoinduction. Although still controversial, there is
      increasing evidence for release of apoptogenic factors through pores in the outer
      mitochondrial membrane, rather than deltapsiloss-dependent membrane rupture, with
      maintenance of mitochondrial function at least in the early phase of the death
      response. GC-induced cell cycle arrest in ALL cells appears to be independent of
      apoptosis induction and vice versa, and critically depends on repression of both
      cyclin-D3 and c-myc followed by increased expression of the cyclin-dependent
      kinase inhibitor, p27Kip1. Since development of GC-resistant clones requires both
      cell cycle progression and survival, GC resistance might frequently result from
      structural or regulatory defects in GR expression, perhaps the most efficient
      means to target both pathways concurrently.

PMID- 14682493
TI  - Bone marrow derived cells for brain repair: recent findings and current
      controversies.
AB  - Adult stem cells were once thought to produce only the cell lineages
      characteristic of the tissues in which they reside. Recent studies suggest that
      cells derived from one adult tissue can be reprogrammed to change into cellular
      phenotypes not normally found in that tissue. Bone marrow (BM) derived cells have
      been demonstrated to differentiate into multiple lineages, including glial cells
      and neurons, both in vivo and in vitro. This unexpected plasticity of BM cells
      occurs not only under experimental conditions, but also in humans following BM
      transplantation. As a result, BM transplantation has emerged as a novel approach
      to enhance neural regeneration and restore injured brain tissue. Several research
      teams have reported that transplanted BM cells can differentiate into neural
      derivatives; indeed, some of these cells were capable of integration into the
      host brain, where they promoted functional recovery after brain injury. Other
      researchers conducting similar studies were unable to find any evidence of neural
      differentiation, concluding that differentiation 'from marrow to brain' is not a
      common phenomenon. More recently, two papers in Nature also cast doubt on the
      plasticity of adult stem cells, suggesting that the acquisition of different
      identities by grafted BM cells may merely reflect their fusion with host cells.
      Reasons for the wide discrepancies among findings in current BM stem cell
      research are unclear, making it difficult to understand the mechanisms by which
      transplanted marrow stem cells provide therapeutic benefit. Here, we summarize
      recent findings on this subject, and address some of the major controversies that
      have marked the evolution of adult stem cell research.

PMID- 14682494
TI  - TRAIL: a potential agent for cancer therapy.
AB  - Induction of apoptosis in cancer cells with chemotherapy and radiation treatment
      is a major strategy in cancer therapy at present. Nevertheless, innate or
      acquired resistance has been an obstacle for conventional clinical therapy. TNF
      related apoptosis inducing ligand (TRAIL/Apo-2L) is a typical member of the TNF
      ligand family that induces apoptosis through activating the death receptors. In
      recent years, considerable attention has been focused on the potential benefits
      of TRAIL in cancer therapy, as the majority of cancer cells are sensitive to
      TRAIL-induced apoptosis, while most normal cells are TRAIL-resistant.
      Furthermore, the use of TRAIL in combination with chemotherapeutic agents or
      irradiation strengthens its apoptotic effects. In this review, we will discuss
      the regulation mechanism of TRAIL-induced apoptosis and the molecular basis of
      the synergies created by its use in combination with chemotherapeutic agents and
      irradiation. We also analyze in detail that TRAIL may be cytotoxic, as this is a
      potential obstacle to its development for being used in cancer therapy.

PMID- 14682495
TI  - Molecular and genetic mechanisms of osteoporosis: implication for treatment.
AB  - Osteoporosis is a leading public health problem in our rapidly growing, aging
      population. It is characterized by reduced bone mass and microarchitectural
      deterioration of bone tissue, with a consequent increase in bone fragility and
      susceptibility to fracture risk. Osteoporosis is a complex multifactorial
      disease, determined by genetic and environmental factors as well as their
      interactions. A large number of molecular, genetic and environmental factors
      underlying osteoporosis have been identified in past decades. In this article, we
      review 1) the molecular mechanisms of several principal systemic and local
      factors regulating bone metabolism; and 2) the current status of genetic studies
      searching for genes underlying osteoporosis. Further, we attempt to integrate
      knowledge from those two fields, and their potential implications for
      osteoporosis treatment.

PMID- 14682496
TI  - Regulation of dendritic cell function through toll-like receptors.
AB  - Higher animals establish host defense by orchestrating innate and adaptive
      immunity. This is mediated by professional antigen presenting cells, i.e.
      dendritic cells (DCs). DCs can incorporate pathogens, produce a variety of
      cytokines, maturate, and present pathogen-derived peptides to T cells, thereby
      inducing T cell activation and differentiation. These responses are triggered by
      microbial recognition through type I transmembrane proteins, Toll-like receptors
      (TLRs) on DCs. TLRs consist of ten members and each TLR is involved in
      recognizing a variety of microorganism-derived molecular structures. TLR ligands
      include cell wall components, proteins, nucleic acids, and synthetic chemical
      compounds, all of which can activate DCs as immune adjuvants.

PMID- 14682497
TI  - Vaccination against angiogenesis-associated antigens: a novel cancer
      immunotherapy strategy.
AB  - Therapeutic vaccines represent an attractive approach to cancer treatment.
      Traditionally, cancer immunotherapy targets antigens expressed by the tumor
      cells. Although numerous clinical trials studying different cancer vaccines have
      been conducted during the past twenty years, very limited clinical responses have
      been observed. The inefficient anti-tumor immunity is thought to be due, in major
      part, to the escape mechanisms exerted by the genetically unstable tumor cells,
      e.g., emergence of antigen-loss mutants, downregulation of MHC molecules and lack
      of expression of costimulatory molecules. Recently, a novel vaccine strategy has
      been developed to circumvent these obstacles. Taking advantage of the importance
      of angiogenesis in tumor growth and the genetic stability of endothelial cells,
      this immunotherapy strategy targets antigens (e.g., angiogenic growth factor
      receptors) overexpressed by the tumor neo-vasculature rather than the tumor cells
      per se. For example, active immunization against vascular endothelial growth
      factor receptor-2 (VEGFR-2) has been shown to generate strong cellular and
      humoral immune responses, which lead to the inhibition of angiogenesis and tumor
      growth and metastasis. This review provides an outline of this emerging field and
      discusses the advantages and potential pitfalls of such a vaccine strategy.

PMID- 14682498
TI  - Outreach, mental health, and case management services: can they help to retain
      HIV-positive and at-risk youth and young adults in care?
AB  - OBJECTIVES: To assess the impact of outreach, mental health, and case management
      services on retention in primary care of HIV+ and at-risk youth and young adult
      clients of the Boston HAPPENS program, a comprehensive adolescent HIV prevention
      and care network of agencies. METHODS: Providers at 8 urban sites used standard
      data forms at each visit to collect background and service receipt information on
      at-risk clients aged 12-24 years. Data were aggregated across all visits for each
      client to create summary variables for the number of times each client received
      each type of service. The retention measure was the number of days between a
      client's first and last visits during the 4-year data collection period. Kaplan
      Meier survival curve and Cox proportional hazards regression analyses were used
      to assess the association between receipt of the support services of interest and
      the retention measure. RESULTS: The median retention times were 21 days for male
      clients (range, 0-1406, N = 512), and 26 days for female clients (range, 0-1577,
      N = 914). Among males, 45% were retained beyond a month, 24% beyond a year, and
      10% beyond 2 years. Similar proportions of females were retained beyond a month
      and a year, but more females were retained beyond 2 years (15%). After adjusting
      for other covariates, both male and female clients had significantly longer
      retention times if they received > or = 2 outreach contacts, or case management
      at > or = 3 visits. Among males, receipt of mental health counseling at > or = 2
      visits also increased retention times. CONCLUSIONS: These findings suggest that
      provision of outreach, mental health, and case management services can improve
      retention in care of at-risk youth and young adults.

PMID- 14682499
TI  - Levels of excess infant deaths attributable to maternal smoking during pregnancy
      in the United States.
AB  - OBJECTIVES: The objectives of the study were: 1) To determine the risk of infant
      mortality associated with prenatal cigarette smoking; 2) To assess whether the
      relationship, if existent, was dose-dependent; 3) To explore the morbidity
      pathway that explains the effect of tobacco smoke on infant mortality, and 4) to
      compute excess infant deaths attributable to maternal smoking in the United
      States. METHODS: Retrospective cohort study on 3,004,616 singleton live births
      that occurred in 1997 in the United States using the US national linked
      birth/infant death data. Excess infant deaths due to maternal smoking were
      computed using the population-attributable risk (PAR). RESULTS: Overall, 13.2% of
      pregnant women who delivered live births in 1997 smoked during pregnancy. The
      rate of infant mortality was 40% higher in this group as compared to nonsmoking
      gravidas (P < 0.0001). This risk increased with the amount of cigarettes consumed
      prenatally in a dose-dependent fashion (p for trend < 0.0001). Small-for
      gestational age rather than preterm birth is the main mechanism through which
      smoking causes excess infant mortality. We estimated that about 5% of infant
      deaths in the United States were attributable to maternal smoking while pregnant,
      with variations by race/ethnicity. The proportion of infant deaths attributable
      to maternal smoking was highest among American Indians at 13%, almost three times
      the national average. If pregnant smokers were to halt tobacco use a total of 986
      infant deaths would be averted annually. CONCLUSIONS: Smoking during pregnancy
      accounts for a sizeable number of infant deaths in the United States. This
      highlights the need for infusion of more resources into existing smoking
      cessation campaigns in order to achieve higher quit rates, and substantially
      diminish current levels of smoking-associated infant deaths.

PMID- 14682500
TI  - Low birth weight across generations.
AB  - OBJECTIVES: This study sought to determine the relationship between maternal
      birth weight, prenatal care usage, and infant birth weight. METHODS: Stratified
      and logistic regression analyses were performed on a dataset of computerized
      Illinois vital records of White (N = 187, 074) and African-American (N = 58,856)
      infants born between 1989 and 1991 and their mothers born between 1956 and 1975.
      RESULTS: Among White mothers who received adequate prenatal care, the low birth
      weight (<2500 g) rate was 4% for infants of former low birth weight mothers (N =
      5230) compared to 2.1% for infants of former nonlow birth weight mothers (N =
      93,011), relative risk equaled 1.9(1.7-2.2); the population attributable risk of
      maternal low birth weight was 4.1%. Among African American mothers who received
      adequate prenatal care, the low birth weight rate was 15% for infants of former
      low birth weight mothers (N = 2196) compared to 7.2% for infants of former nonlow
      birth weight mothers (N = 14,607), relative risk equaled 2.1(1.9-2.4); the
      population attributable risk of maternal low birth weight was 10.9%. The maternal
      infant birth weight associations were consistent across all maternal age,
      education, marital status, and prenatal care categories. CONCLUSIONS: Maternal
      low birth weight is a risk factor for infant low birth weight independent of risk
      status during the current pregnancy. A greater percentage of low birth weight
      African American (compared to White) infants are attributable to maternal low
      birth weight.

PMID- 14682501
TI  - Selection bias in prenatal care use by Medicaid recipients.
AB  - OBJECTIVE: This study examines whether four types of selection bias in estimates
      of the effectiveness of prenatal care utilization for improving birthweight occur
      in a population of economically disadvantaged women. METHODS: We categorized
      adequacy of prenatal care use using the Adequacy of Prenatal Care Utilization
      Index (APNCU) and the Revised-GINDEX for 142,381 Medicaid recipients who gave
      birth to a live, singleton infant in Washington State (1994-1998). Multinomial
      logistic regression was used to model categories of adequacy of prenatal care use
      as functions of variables chosen to indicate high- or low-risk status. A series
      of linear regression models were estimated to quantify the magnitude and
      direction of any bias in the effects of prenatal care on birthweight that could
      be attributed to accounting for each risk covariate. Results were examined for
      patterns of risk, prenatal care use, and estimation bias equated with the four
      selection processes. RESULTS: We found modest evidence of adverse, favorable,
      confidence, and estrangement selection biases. The overriding effect, relative to
      low prenatal care use, was overestimation of the adequate care coefficient by
      8.68 g with the APNCU, and underestimation by 3.36 g with the R-GINDEX because of
      competing confidence and estrangement selection biases. Relative to intensive
      use, the effect of adequate care on birthweight was underestimated (17.58 g with
      the APNCU; 13.34 g with the R-GINDEX) because of adverse selection bias and a
      small countervailing favorable selection process. CONCLUSIONS: The
      underestimation of birthweight associated with prenatal care noted in prior
      studies appears to result from multiple selection processes working in different
      directions. Understanding selection processes can help the assessment of the
      contribution of prenatal care to birth outcomes and development of appropriate
      programs and policies.

PMID- 14682502
TI  - Interdisciplinary leadership training outcomes of Maternal and Child Health
      funded pediatric pulmonary centers.
AB  - OBJECTIVES: To describe career paths, leadership accomplishments, and extent of
      incorporation of Maternal and Child Health Bureau (MCHB) values into professional
      activities of all previous long-term trainees. METHOD: In 1998 the Pediatric
      Pulmonary Centers (PPCs) completed a Leadership Training Outcomes Survey of all
      previous long-term trainees. The survey included 1) characteristics, 2) career
      paths, 3) current professional activities, 4) leadership roles and activities,
      and 5) career incorporation of MCHB values. RESULTS: There was a 63% response
      rate (N = 274) from 431 mailed surveys. Most respondents provided clinical care
      in varied health-related settings. Of the respondents, 44% (N = 120) served
      mothers, 87% (N = 239) served children, and 78% (N = 214) served children with
      special health care needs. Forty-seven percent of the mothers and children served
      were from racial or ethnic minority groups. Ninety-two percent (N = 252) of
      respondents had conducted training since graduation and 56% (N = 153) had
      provided technical assistance. Many provided leadership in the acquisition and
      dissemination of new knowledge through research publication (33%), advocacy
      (37%), and program administration/oversight (87%). Thirty percent of the
      respondents (N = 83) had received special recognition awards for professional
      activities. CONCLUSIONS: Most PPC graduates serve families and children as a
      central aspect of their career, providing or enhancing family-centered, community
      based, culturally competent, comprehensive interdisciplinary care.

PMID- 14682503
TI  - The shifting sands for applicants to maternal and child health training programs.
AB  - OBJECTIVE: Anecdotal evidence suggests that fewer students today than in decades
      past are applying to maternal and child health (MCH) graduate training programs
      with previous clinical degrees. The purpose of this study was to determine the
      extent to which applicants accepted to an MCH training program demonstrated a
      shift away from the tradition of having a prior health professional degree and
      discuss options needed to provide responsive training. METHODS: Twenty years of
      demographic face sheet data (1983 through 2002) for admitted applicants to the
      MCH training program at the University of South Florida College of Public Health
      were examined. RESULTS: Quantitative analysis of admission records confirmed the
      anecdotal data. Today's applicants are more likely to possess undergraduate
      nonclinical backgrounds rather than clinical health professional training.
      Statistically significant differences were found between the students with
      clinical and without clinical degrees for ethnicity, GRE score, GPA, and the
      length of time needed to complete the MPH degree. CONCLUSION: Adjustments in MCH
      curricula may be necessary to be responsive to the "shifting sands" of clinical
      and public health work experience among program applicants. However, curriculum
      modifications need to be ones that maintain the zeal of the new generation of MCH
      students without diluting the rigor of traditional professional preparation. Some
      possible responses of training programs are suggested.

PMID- 14682504
TI  - The new MCH student: why can't they be like we were?

PMID- 14682505
TI  - Bioactivity, synthesis, and chirality of the sex pheromone of currant stem
      girdler, Janus integer.
AB  - It was previously reported that females of the currant stem girdler, Janus
      integer Norton (Hymenoptera: Cephidae), produce a compound, (Z)-9-octadecen-4
      olide (1), that is sensitively detected by the antennae of males only. These
      characteristics suggested a pheromonal function, and this has now been confirmed
      with behavioral tests. Field tests conducted during two seasons in a commercial
      red currant field in Washington State showed that synthetic racemic 1 is
      attractive to male J. integer under natural conditions. A clear dose-response was
      evident, with greatest numbers of girdlers caught in sticky traps baited with 10
      mg of the pheromone (in rubber septa) and least in traps baited with 1 mg or
      less. During May 2002, 10, 5, 3, and 1 mg baited traps caught means of 41.4,
      26.6, 6.7, and 2.7 males/trap/visit (3-5 day intervals), respectively, with a
      maximum of 229 males caught in a single trap baited with 5 mg. A new synthetic
      method for racemic 1 is presented. The absolute configuration of natural 1 from
      the male sawflies was determined to be (R). The potential for using the sex
      pheromone of J. integer to improve management of this currant and gooseberry pest
      is discussed.

PMID- 14682506
TI  - Enantiomers of (Z,Z)-6,9-heneicosadien-11-ol: sex pheromone components of Orgyia
      detrita.
AB  - (6Z,9Z,11S)-6,9-Heneicosadien-11-ol (Z6Z9-11S-ol-C21) and (6Z,9Z,11R)-6,9
      heneicosadien-11-ol (Z6Z9-11R-ol-C21) were identified as major sex pheromone
      components of female tussock moths, Orgyia detrita Guerin-Meneville (Lepidoptera:
      Lymantriidae), on the basis of (1) analyses of pheromone gland extracts of female
      O. detrita by coupled gas chromatographic-electroantennographic detection (GC
      EAD) and GC mass spectrometry, and (2) field trapping experiments with synthetic
      standards. Z6Z9-11S-ol-C21 and Z6Z9-11R-ol-C21 in combination, but not singly,
      attracted significant numbers of male moths. Racemic Z6Z9-11-ol-C21 was more
      attractive than the 1:3.5 (R:S) blend ratio found in pheromone gland extracts
      from female moths. Lower and higher homologues of Z6Z9-11-ol-C21 were also
      detected in GC-EAD recordings of pheromone extracts, and the racemic compounds
      enhanced attractiveness of Z6Z9-11-ol-C21 in field experiments. Because of trace
      amounts of these homologues in extracts, their enantiomeric composition could not
      be determined. This is the first report of secondary alcohols as pheromone
      components in the ditrysian (advanced) Lepidoptera.

PMID- 14682507
TI  - Identification of a sex pheromone component of Pseudococcus cryptus.
AB  - A sex pheromone component of Pseudococcus cryptus has been isolated and
      identified. The crude pheromone extract obtained by airborne collection was
      fractionated by liquid chromatography (LC) on Florisil, and further purified by
      high performance liquid chromatography and preparative Gas Chromatography (GC).
      The pheromone component was shown to be an ester, the alcohol part of which was
      identical to the known alcohol moiety of the pheromone of Planococcus citri. The
      chemical structure was determined to be 3-isopropenyl-2,2
      dimethylcyclobutylmethyl 3-methyl-3-butenoate by MS and 1H NMR analyses. The
      absolute configuration of the pheromone was assigned as (1R,3R) by comparison of
      the retention time of the alcohol derived from the P. cryptus pheromone with
      those of the alcohol derived from P. citri pheromone, and a synthetic sample of
      alcohol enriched in the (1R,3R)-enantiomer, using a chiral GC stationary phase.
      The structure of the pheromone was confirmed by synthesis, and by bioassays in a
      glasshouse.

PMID- 14682509
TI  - Mammalian exocrine secretions. XVIII: Chemical characterization of interdigital
      secretion of red hartebeest, Alcelaphus buselaphus caama.
AB  - Gas chromatography, coupled gas chromatography-mass spectrometry (electron impact
      mode and chemical ionization with methane as reactant gas), gas chromatography
      infrared spectroscopy, and derivatization techniques were used to identity 53
      compounds in the interdigital secretion of the red hartebeest, Alcelaphus
      buselaphus caama. These compounds included alkanes, isoalkanes, alcohols,
      ketones, carboxylic acids, oxiranes, furanoid linalool oxides, and a large number
      of branched and unbranched saturated and unsaturated aldehydes. The secretion
      probably plays a role in demarcation of territories by dominant bulls.

PMID- 14682508
TI  - Responses of the aphids Phorodon humuli and Rhopalosiphum padi to sex pheromone
      stereochemistry in the field.
AB  - Gynoparous female and male damson-hop aphids, Phorodon humuli (Schrank), were
      caught in the field by water traps that were releasing the sex pheromone of this
      species, (1RS,4aR,7S,7aS)-nepetalactol. No behavioral activity was elicited by
      (4aS,7S,7aR)-nepetalactone, the major sex pheromone component of other aphid
      species such as Megoura viciae Buckton, even though olfactory cells were found in
      the secondary rhinaria on the third antennal segment of P. humuli that responded
      strongly to this compound. Gynoparous female P. humuli in the field responded
      less strongly to (1R,4aS,7S,7aR)-nepetalactol, the sex pheromone of the bird
      cherry-oat aphid, Rhopalosiphum padi (L.), than they did to the (4aR,7S,7aS)
      nepetalactols, but males responded only to the latter. The (4aR,7S,7aS)
      nepetalactone showed no electrophysiological activity so was not used in field
      trials. Releasing either the (4aS,7S,7aR)-nepetalactone or the (1R,4aS,7S,7aR)
      nepetalactol with the (4aR,7S,7aS)-nepetalactols did not inhibit the response of
      P. humuli gynoparous females and males to the latter. Males of R. padi responded
      as strongly to the (4aR,7S,7aS)-nepetalactols as they did to (1R,4aS,7S,7aR)
      nepetalactol. Males of P. humuli and R. padi responded positively to an increased
      concentration of the (4aR,7S,7aS)-nepetalactols released from two vials compared
      with that from a single vial, as did P. humuli (in one of two experiments) and R.
      padi to the (1RS,4aR,7S,7aS)- and (1R,4aS,7S,7aR)-nepetalactols when released
      together.

PMID- 14682510
TI  - Synergism of polygodial and trans-cinnamic acid on inhibition of root elongation
      in lettuce seedling growth bioassays.
AB  - A bicyclic sesquiterpene dialdehyde, polygodial did not inhibit root elongation
      up to a concentration of 12.5 microg/ml in a lettuce seedling assay: trans
      Cinnamic acid inhibited the elongation by 50% at 1.2 microg/ml (8.1 microM). The
      inhibitory activity of trans-cinnamic acid was enhanced 17-fold when used in
      combination with 6.25 microg/ml (26.5 microM) of polygodial. A decrease in the pH
      of the medium was observed during normal seedling growth, indicating transport of
      protons from the cells by a plasma membrane H+-ATPase. The inhibitory effect of
      trans-cinnamic acid on the elongation was reduced to some extent in 2 mM
      phosphate buffer (pH 7.0) during seedling growth. Although polygodial did not
      inhibit the activity of H+-ATPase in the plasma membrane fraction of roots in
      normally growing seedlings, a decrease in activity was found in the fraction
      obtained from seedlings incubated with 20 microg/ml of polygodial. These results
      suggest that polygodial functions synergistically with trans-cinnamic acid in the
      inhibition of root elongation via restriction of proton transport from the
      cytoplasm of germinated cells.

PMID- 14682511
TI  - Correlation between phytotoxicity on annual ryegirass (Lolium rigidum) and
      production dynamics of allelochemicals within root exudates of an allelopathic
      wheat.
AB  - An improved allelopathic correlation between phytotoxicity measured in root
      growth bioassay upon annual ryegrass (Lolium rigidum Gaud.) and the
      concentrations of a selection of dynamically produced allelochemicals quantified
      in the root exudates of cv. Khapli wheat (Triticum turgidum ssp. durum (Desf.)
      Husn.) monitored during the first 15 days of wheat seedling growth in a sterile,
      agar-water medium, has been established. Changes over the 15-day growth period in
      the quantities of five exuded benzoxazinones and seven phenolic acids were
      measured simultaneously using GC/MS/MS. Substantiating pure compound dose
      response measurements were conducted over a range of concentrations for the
      putative allelochemicals within the wheat exudates. One synergism-based proposal
      using the monitored compounds to explain the observed low-exudate-concentration
      phytotoxicity was explored, but was found to be experimentally inadequate.

PMID- 14682512
TI  - Effects of monoterpenoids, acting alone or in pairs, on seed germination and
      subsequent seedling growth.
AB  - We compared the potential allelopathic activity of 47 monoterpenoids of different
      chemical groups, by estimating their effect on seed germination and subsequent
      growth of Lactuca sativa seedlings. Apart from individual compounds, eleven pairs
      at different proportions were also tested. As a group, the hydrocarbons, except
      for (+)-3-carene, were the least inhibitory. Of the oxygenated compounds, the
      least inhibitory were the acetates; whenever the free hydroxyl group of an
      alcohol turned into a carboxyl group, the activity of the resulting ester was
      markedly lower (against both germination and seedling growth). Twenty-four
      compounds were extremely active against seedling growth (inhibiting it by more
      than 85%), but only five against seed germination. The compounds that were most
      active against both processes belonged to the groups of ketones and alcohols;
      they were terpinen-4-ol, dihydrocarvone, and two carvone stereoisomers. We used a
      model to investigate whether compounds acted independently when applied in pairs.
      The combined effect varied. In half of the cases, it followed the pattern
      expected under the assumption of independence; in the rest, either synergistic or
      antagonistic interactions were found in both germination and elongation. However,
      even in cases of synergistic interactions, the level of inhibition was not
      comparable to that of a single extremely active compound, unless such a compound
      already participated in the combination. The specific structural factors that
      operate and determine the activity of monoterpenoids still remain rather obscure.
      The same holds true for the combined effect; its character cannot in general be
      predicted on the basis of individual compounds acting alone.

PMID- 14682513
TI  - Behavioral foraging responses by the butterfly Heliconius melpomene to Lantana
      camara floral scent.
AB  - Floral color has been shown to influence flower selection by butterflies, but few
      studies have investigated the role of floral scent. In this study, adults of
      Heliconius melpomene L. (Lepidoptera: Nymphalidae: Heliconiinae) were tested in
      two-choice bioassays to investigate their ability to distinguish floral scent of
      the butterfly pollinated plant Lantana camara L. (Verbenaceae) from other plant
      scents. The relative importance of floral scent vs. color was also studied.
      Butterfly foraging behavior was measured as probing with proboscis. This probing,
      on floral models varying in scent and color, was timed. When given a choice of
      floral and vegetative scents of L. camara, newly emerged butterflies preferred
      floral scent, indicating an innate response to floral scents. When butterflies
      were conditioned to L. camara floral scent by offering the scent with yellow
      color and sugar water, yellow color elicited stronger feeding responses than did
      the floral scent. However, the floral scent of L. camara was preferred to that of
      the novel species Philadelphus coronarius L. (Hydrangiaceae). The floral scent of
      L. camara was dominated by tepenoid compounds, while that of P. coronarius by
      fatty acid derivatives, thus demonstrating totally different compositions. It is
      concluded that, while H. melpomene butterflies often use visual floral traits
      when selecting which flowers to visit, floral scents elicit behavioral responses
      that initiate and maintain foraging on flowers.

PMID- 14682514
TI  - Antennal responses to floral scents in the butterfly Heliconius melpomene.
AB  - Floral scent, together with visual floral cues, are important signals to adult
      butterflies searching for food-rewarding plants. To identify which compounds in a
      floral scent are more attractive and, thus, of biological importance to foraging
      butterflies, we applied electrophysiological methods. Antennal responses of male
      and female adults of the tropical butterfly Heliconius melpomene L. (Lepidoptera:
      Nymphalidae: Heliconiinae) to individual compounds of natural floral scents and
      synthetic floral scent mixtures were investigated using gas chromatography
      electroantennographic detection (GC-EAD). The natural floral scents included
      those of two tropical plant species, Lantana camara L. (Verbenaceae) and
      Warszewiczia coccinea (Vahl) Kl. (Rubiaceae), and two temperate species, Buddleja
      davidii Franchet (Loganiaceae) and Cirsium arvense (L.) Scop. (Asteraceae). The
      two synthetic floral scent mixtures contained many of the compounds found in the
      natural scents, but all in equal quantities. Compounds both present in relatively
      high abundance in the floral scents and detected exclusively in the floral parts
      of the plant, such as linalool, linalool oxide (furanoid) I and II,
      oxoisophoroneoxide, and phenylacetaldehyde, elicited the strongest antennal
      responses, suggesting that they may reflect adaptations by the plant to attract
      butterfly pollinators. However, other compounds also present in high abundance in
      the floral scent, but detected in the vegetative as well as floral plant parts,
      either elicited strong antennal responses, such as trans-beta-ocimene and
      benzaldehyde, or failed to elicit antennal responses, such as the sesquiterpenes
      beta-caryophyllene and alpha-humulene from L. camara. The most volatile
      monoterpene alkenes in the synthetic scent mixtures elicited only low or no
      responses. Furthermore, the overall antennal responses were stronger in females
      than in males. The findings suggest that several floral scent volatiles,
      especially those of exclusively floral origin, are of high biological
      significance to H. melpomene butterflies. These include compounds of different
      biosynthetic origins belonging to the benzenoids, monoterpenoids, and irregular
      terpenoids.

PMID- 14682516
TI  - Identification of host fruit volatiles from flowering dogwood (Cornus florida)
      attractive to dogwood-origin Rhagoletis pomonella flies.
AB  - Solid-phase microextraction and gas chromatography coupled with
      electroantennographic detection were used to identify volatiles from fruit of
      flowering dogwood, Cornus florida, as key attractants for Rhagoletis pomonella
      flies originating from dogwood fruit. A six-component blend containing ethyl
      acetate (54.9%), 3-methylbutan-1-ol (27.5%), isoamyl acetate (0.9%), dimethyl
      trisulfide (1.9%), 1-octen-3-ol (9.1%), and beta-caryophyllene (5.8%) was
      identified from flowering dogwood fruit that gave consistent EAD activity. In a
      flight tunnel assay there was no significant difference in the response of
      individual dogwood flies exhibiting upwind anemotactic flight to volatile
      extracts from dogwood fruit and the six-component synthetic mixture. Dogwood
      flies also displayed significantly greater levels of upwind flight to sources
      with the dogwood volatile blend than with previously identified volatile blends
      from domestic apple or hawthorn fruit. Selected subtraction assays showed that
      the three-component mixture of 3-methylbutan-1-ol, 1-octen-3-ol, and beta
      caryophyllene elicited levels of upwind flight to the source equivalent to the
      six-component mixture. Our study adds to previous ones showing that populations
      of Rhagoletis pomonella flies infesting apple, hawthorn, and flowering dogwood
      fruit are attracted to unique mixtures of fruit volatiles, supporting the
      hypothesis that host fruit odors could be key traits in sympatric host shifts and
      establishing host fidelity within members of the Rhagoletis pomonella species
      complex.

PMID- 14682515
TI  - Responses of Glossina morsitans morsitans to blends of electroantennographically
      active compounds in the odors of its preferred (buffalo and ox) and nonpreferred
      (waterbuck) hosts.
AB  - In a previous study, comparison of the behavior of teneral Glossina morsitans
      morsitans on waterbuck, Kobus defassa (a refractory host), and on two preferred
      hosts, buffalo, Syncerus caffer, and ox, Bos indicus, suggested the presence of
      allomones in the waterbuck odor. Examination of the volatile odors by coupled gas
      chromatography-electroantennographic detection showed that the antennal receptors
      of the flies detected constituents common to the three bovids (phenols and
      aldehydes), as well as a series of compounds specific to waterbuck, including C8
      C13 methyl ketones, delta-octalactone, and phenols. In this study, behavioral
      respones of teneral G. m. morsitans to different blends of these compounds were
      evaluated in a choice wind tunnel. The flies' responses to known or putative
      attractant blends (the latter comprising EAG-active constituents common to all
      three animals and those common to buffalo and ox, excluding the known tseste
      attractants, 4-methylphenol and 3-n-propylphenol), and to putative repellent (the
      blend of EAG-active compounds specific to the waterbuck volatiles), were
      different. A major difference related to their initial and final behaviors. When
      a choice of attractant blends (known or putative) and clean air was presented,
      flies initially responded by flying upwind toward the odor source, but later
      moved downwind and rested on either side of the tunnel, with some preference for
      the side with the odor treatments. However, when presented with a choice of
      waterbuck-specific blend (putative repellent) and clean air, the flies' initial
      reaction appeared random; flies flew upwind on either side, but eventually
      settled down on the odorless side of the tunnel. Flies that flew up the odor
      plume showed an aversion behavior to the blend. The results lend further support
      to previous indications for the existence of a tsetse repellent blend in
      waterbuck body odor and additional attractive constituents in buffalo and ox body
      odors.

PMID- 14682517
TI  - Hostplant suitability and defensive chemistry of the Catalpa sphinx, Ceratomia
      catalpae.
AB  - The growth and survival of the Catalpa sphinx, Ceratomia catalpae (Sphingidae),
      were measured on five different species of Catalpa: C. bignonioides, C. bungeii,
      C. fargeseii, C. ovata, and C. speciosa. Larval growth varied significantly among
      these host plant species; however, survival did not differ. Quantification of the
      iridoid glycoside content of larvae, pupae, adults, larval frass, and leaves of
      the larval host plant, C. bignonioides, by gas chromatography showed that leaves
      contained both catalpol and catalposide; larvae, pupae, and frass contained only
      catalpol; and the adults contained no detectable iridoid glycosides. Amounts were
      highest in the larvae and declined in the pupal stage. Very small amounts of
      catalpol were detected in adults of the parasitoid, Cotesia congregata, and in
      the silken cocoons. The hemolymph in which the parasitoid larvae grew contained
      over 50% dry weight catalpol. Larvae of C. catalpae often regurgitate when
      disturbed. This may serve as a defense against predators. A comparison of the
      growth of larvae pinched with forceps to induce regurgitation with those that
      were not so treated showed that larvae that were pinched, and usually
      regurgitated, grew significantly more slowly than those that were not.

PMID- 14682518
TI  - Comparative benzene-induced fatty acid changes in a Rhodococcus species and its
      benzene-sensitive mutant: possible role of myristic and oleic acids in tolerance.
AB  - A Gram positive bacterium of the genus Rhodococcus was isolated from a
      contaminated site in Sydney, Australia, for its ability to tolerate and degrade
      high concentrations of benzene. To identify fatty acids that may impart this
      Rhodococcus sp. with tolerance to toxic solvents, a benzene-sensitive strain,
      labeled M2b, was isolated using EMS mutagenesis. A comparative analysis of fatty
      acid profiles showed that strain M2b was unable to increase its
      saturated:unsaturated ratio of fatty acids to the level achieved by the w-t
      strain when both strains were challenged with benzene. This was due to M2b's
      increased abundance of myristic acid, and decreased abundance of oleic acid. In
      addition, by measuring the generalized polarization of the fluorescent membrane
      probe laurdan using fluorescence spectroscopy, we have shown for the first time
      the effects of an aromatic hydrocarbon on the membrane fluidity of a Rhodococcus
      sp. The fluidity of the membranes increased after only 0.5 hr of exposure to
      benzene, thus suggesting the partitioning of benzene within the lipid bilayer.
      The response of this Rhodococcus sp. to benzene may suggest a mechanism for how
      other microorganisms survive when toxic solvents are released within the vicinity
      of their environment.

PMID- 14682519
TI  - Attraction of the fruit-eating bat Carollia perspicillata to Piper
      gaudichaudianum essential oil.
AB  - We performed field tests using mimetic Piper fruits with and without essential
      oil extracted through hydrodistillation from Piper gaudichaudianum ripe fruits in
      order to evaluate the role of odor in Carollia perspicillata attraction and
      capture in mist-nets. During the field tests, 26 C. perspicillata were captured,
      21 (80.7%) in nets with the essential oil of P. gaudichaudianum and five (19.3%)
      in nets without oil. Other bat species, Artibeus spp. (67), which is specialized
      on fruits of Moraceae, and Sturnira lilium (10), specialized on those of
      Solanaceae, were also captured, but they exhibited no significant preference for
      nets with or without oil. We conclude that odor is pre-eminent over visual cues
      in food location by C. perspicillata in a field situation. Based on the result,
      we propose the extraction and use of essential oils of chiropterochoric fruits as
      a useful approach to improve autoecological studies on fruit-eating bats and to
      promote tropical forest restoration through the attraction of frugivorous bats to
      degraded areas.

PMID- 14682520
TI  - Analysis of anal droplets of the western flower thrips Frankliniella
      occidentalis.
AB  - Larvae of the western flower thrips Frankliniella occidentalis are known to
      produce an anal droplet containing decyl acetate (10Ac) and dodecyl acetate
      (12Ac), which act as an alarm pheromone. Analysis by GC showed that the combined
      mass of 10Ac and 12Ac per droplet increased with age of second instars from 2 ng
      to 18 ng, while the mass ratio of 10Ac:12Ac increased from 0.4:1 to 1.1:1 (molar
      ratio 0.4:1 to 1.2:1). Droplet volume increased from 0.4 nl to 2.1 nl with age,
      but only about 1% of this was accounted for by 10Ac and 12Ac. The remainder
      contained water. Analysis by GC-MS using SPME revealed no other volatile
      components. Whole bodies contained about two to four times as much 10Ac and 12Ac
      as a droplet, but in a similar ratio.

PMID- 14682521
TI  - Sex pheromone of the leaf-miner Phyllonorycter platani: (Z10)-tetradecenyl
      acetate.
AB  - A female produced sex pheromone of the leaf-miner pest Phyllonorycter platani
      (Staudinger) (Lepidoptera: Gracillariidae) was identified as (Z10)-tetradecenyl
      acetate. Field trapping trials confirmed activity of this compound. The presence
      of the geometrical isomer (E10)-tetradecenyl acetate, a pheromone component of
      other Phyllonorycter species, reduced trap efficacy.

PMID- 14682522
TI  - Intraspecific and interspecific interactions mediated by a phytotoxin, (-)
      catechin, secreted by the roots of Centaurea maculosa (spotted knapweed).
AB  - Centarea maculosa Lam. (spotted knapweed) is one of the most destructive invasive
      weeds in the western United States, particularly in pastures and rangelands. One
      of the components that may contribute to its invasiveness is the naturally
      produced, root-secreted allelochemical (-)-catechin. This compound has been shown
      to have broad-spectrum phytotoxic activity, possibly assisting C. maculosa in
      displacing native plant communities. As a recently characterized phytochemical,
      little is known about the specific effect of (-)-catechin on either C. maculosa
      or other plant species. We have found that, in vitro, C. maculosa begins to
      secrete phytotoxic levels of (-)-catechin within 2-3 weeks of seedling emergence.
      Furthermore, (-)-catechin concentrations consistent with those naturally secreted
      by C. maculosa were sufficient to inhibit germination in all species tested,
      including C. maculosa. These concentrations were also often either phytotoxic or
      growth inhibitory to seedlings in a range of plant species, while having no
      negative effects on the growth of C. maculosa seedlings. However, our results
      also indicate that different levels of resistance and susceptibility to (-)
      catechin exist in plant populations, suggesting that the capability of C.
      maculosa to invade an area through allelochemistry may be dependent on the age
      and species composition of plants in that area.

PMID- 14682523
TI  - Physiological assessment and path coefficient analysis to improve evaluation of
      alfalfa autotoxicity.
AB  - Reseeding of alfalfa is affected until autotoxic chemicals break down or are
      dispersed, often requiring a year or more. Bioassays of seed germination and
      early seedling growth, on agar medium in petri dishes, were conducted to evaluate
      autotoxic responses of 20 alfalfa germplasms to water-soluble extracts of alfalfa
      leaf tissue. Root length, 120 hr after placing imbibed seed on agar, was more
      sensitive to the autotoxin(s) than was hypocotyl length, germination speed, and
      final germination percentage. Path coefficient analyses showed variation in root
      length had 7-17 times more effect than variation in hypocotyl length in
      determining autotoxic effects on total seedling length. Although variations in
      seed size and germination rate were negatively associated (P < 0.05) with final
      root length, the autotoxin had little effect on these factors relative to that on
      root length. Germplasms in the control differed (P < 0.05) in root length,
      requiring tolerance to be evaluated as percent of control. Germplasms, as percent
      of control, differed significantly (P < 0.05) at extract concentrations of 1.0
      and 4.0 g l(-1), but the range and LSD were more favorable for selection at 1.0 g
      l(-1). Root length is appropriate for genetic assessments of tolerance to the
      autotoxin when expressed as percent of control.

PMID- 14682524
TI  - Isolation and structural characterization of a water-soluble germination
      inhibitor from Scotch thistle (Onopordum acanthium) cypselas.
AB  - Cypsela dormancy in Scotch thistle (Onopordum acanthium) may be affected by the
      presence of chemical inhibitors. To investigate this phenomenon, a leachate from
      O. acanthium cypselas was tested for its ability to inhibit germination of the
      cypselas from which it was derived (i.e., autoinhibition). Leachates varied in
      their degree of autoinhibition, depending on the cypsela population from which
      they were prepared. Overall, removal of leachate from a group of O. acanthium
      cypselas increased their germinability. Using lettuce (Lactuca sativa) cypselas
      as an indicator species, bioactivity-guided fractionation was used to isolate a
      water-soluble, para-substituted benzamide from O. acanthium cypselas, which
      caused germination inhibition. Various chromatographic, spectroscopic, and
      spectrometric techniques were applied to the characterization of the bioactive
      compound.

PMID- 14682525
TI  - L-leucine methyl ester: the female-produced sex pheromone of the scarab beetle,
      Phyllophaga lanceolata.
AB  - The female-produced sex pheromone of the scarab beetle Phyllophaga lanceolata was
      identified as the methyl ester of an essential amino acid, L-leucine. During
      field testing, 239 male P. lanceolata were caught in traps baited with L-leucine
      methyl ester. L-Isoleucine and L-valine methyl esters, similar in structure to L
      leucine methyl ester and previously identified as female-produced sex pheromone
      compounds employed by other Phyllophaga species, were also tested. Addition of L
      valine or L-isoleucine methyl esters to the L-leucine methyl ester in 1:1 ratios
      completely inhibited attraction of P. lanceolata males. Males of P. squamipilosa
      were also captured using L-leucine methyl ester. This is the first record of P.
      squamipilosa from Kansas.

PMID- 14682526
TI  - Sex pheromone of the persimmon fruit moth, Stathmopoda masinissa: identification
      and laboratory bioassay of (4E, 6Z)-4,6-hexadecadien-1-ol derivatives.
AB  - Three electroantennogram (EAG)-active components were detected by gas
      chromatography coupled to an electroantennographic detector (GC-EAD) analysis of
      a hexane extract of the pheromone glands of the persimmon fruit moth, Stathmopoda
      masinissa. These compounds were identified as (4E,6Z)-4,6-hexadecadienal (E4,Z6
      16:Ald) and the corresponding acetate (E4,Z6-16:OAc) and alcohol (E4,Z6-16:OH) by
      mass spectral, GC retention time (RT), and microchemical test data. The
      characteristic base peak of the aldehyde at m/z 84 provided a crucial piece of
      information suggesting the possibility of a 4,6-diene structure. The (4E,6Z)
      isomer elicited the strongest EAG responses among the four geometrical isomers of
      each synthetic 4,6-hexadecadienyl compound. In a laboratory bioassay, only E4,Z6
      16:OAc elicited male moth behavioral activity significantly different from the
      control; the activity of the acetate was not affected by addition of the aldehyde
      and alcohol. A preliminary field trial confirmed that E4,Z6-16:OAc as a single
      component attracted male moths. The possible roles of E4,Z6-16:Ald and E4,Z6
      16:OH as components of lures for field use remain to be determined.

PMID- 14682527
TI  - Field trials with the synthetic sex pheromone of the oak processionary moth
      Thaumetopoea processionea.
AB  - The biological activity of synthetic (Z,Z)-11,13-hexadecadienyl acetate, the
      major pheromone component found in female gland extracts of the oak processionary
      moth Thaumetopoea processionea, was evaluated in field trials. Traps baited with
      10 mg of the chemical efficiently attracted a large number of males provided they
      were placed in the upper crown region of the oaks. Devices positioned 10-15 m
      high in the trees attracted significantly more males than those traps installed
      at 2 or 6-8 m above the ground. Pherocon traps were slightly more efficient than
      Delta traps, and lower or higher amounts of the attractant in the baits did not
      significantly influence the number of moths caught. The importance of the
      stereomeric purity of the lure and the easy isomerization of the (Z,Z)-acetate to
      other isomers, particularly to the E,E isomer, should be considered for the
      development of efficient formulations in the field.

PMID- 14682528
TI  - (S)-2,3-dihydrofarnesoic acid, a new component in cephalic glands of male
      European beewolves Philanthus triangulum.
AB  - The chemical composition and functional significance of pheromones of solitary
      Hymenoptera is much less well known compared to social species. Males of the
      genus Philanthus (Sphecidae) are territorial and scent mark their territories to
      attract females. Because of inconsistent results of earlier studies, we
      reanalyzed the content of the cephalic glands of male European beewolves,
      Philanthus triangulum F. Besides a variety of alkanes and alkenes, four major
      compounds were found. Two of these, (Z)-11-eicosen-1-ol and (Z)-10-nonadecen-2
      one, had been previously described as constituents of the cephalic glands. We
      identified 1-octadecanol as a new component of the cephalic gland, and a fourth
      compound, enantiopure (S)-2,3-dihydrofamesoic acid, was identified for the first
      time in nature. Structural elucidation and enantiomeric analysis were performed
      by HRGC-MS and HRGC-FTIR as well as enantioselective gas chromatography and by
      means of authentic reference compounds. Occurrence and function of the four
      compounds in insect chemistry are discussed.

PMID- 14682529
TI  - Olfactory sensitivity of the gilthead seabream (Sparus auratus L) to conspecific
      body fluids.
AB  - The potential for intraspecific chemical communication in the gilthead seabream
      (a marine perciform) was investigated by assessing the olfactory sensitivity to
      conspecific body-fluids (water occupied by conspecifics, intestinal fluid, urine,
      semen, egg fluid) by multiunit electrophysiological recording from the olfactory
      nerve. The olfactory system was responsive to water previously occupied by
      conspecifics, and the active compound(s) could be extracted by solid-phase
      extraction. The olfactory system was extremely sensitive to body fluids of
      sexually mature conspecifics: thresholds of detection were 1:10(7.4) (intestinal
      fluid), 1:10(6.1) (gametes), and 1:10(4.2) (urine). The olfactory system was also
      sensitive to amino acids with thresholds of detection from 10(-8.1) M (L-leucine)
      to 10(-6.1) M (L-phenylalanine). However, a range of other known fish odorants
      (steroids, bile acids, and prostaglandins) failed to evoke significant responses.
      Given the high olfactory sensitivity to intestinal fluid and the low urine
      release rates of marine compared with freshwater fish, we suggest that chemical
      communication is likely to be mediated via compounds present in the intestinal
      fluid rather than urine. Furthermore, the types of chemicals involved are likely
      to be different from those of freshwater fish. Their exact chemical identity and
      biological roles remain to be established.

PMID- 14682530
TI  - Synergistic effects of three Piper amides on generalist and specialist
      herbivores.
AB  - The tropical rainforest shrub Piper cenocladum, which is normally defended
      against herbivores by a mutualistic ant, contains three amides that have various
      defensive functions. While the ants are effective primarily against specialist
      herbivores, we hypothesized that these secondary compounds would be effective
      against a wider range of insects, thus providing a broad array of defenses
      against herbivores. We also tested whether a mixture of amides would be more
      effective against herbivores than individual amides. Diets spiked with amides
      were offered to five herbivores: a naive generalist caterpillar (Spodoptera
      frugiperda), two caterpillar species that are monophagous on P. cenocladum (Eois
      spp.), leaf-cutting ants (Atta cephalotes), and an omnivorous ant (Paraponera
      clavata). Amides had negative effects on all insects, whether they were naive,
      experienced, generalized, or specialized feeders. For Spodoptera, amide mixtures
      caused decreased pupal weights and survivorship and increased development times.
      Eois pupal weights, larval mass gain, and development times were affected by
      additions of individual amides, but increased parasitism and lower survivorship
      were caused only by the amide mixture. Amide mixtures also deterred feeding by
      the two ant species, and crude plant extracts were strongly deterrent to P.
      clavata. The mixture of all three amides had the most dramatic deterrent and
      toxic effects across experiments, with the effects usually surpassing expected
      additive responses, indicating that these compounds can act synergistically
      against a wide array of herbivores.

PMID- 14682531
TI  - Associative olfactory learning of honeybees to differential rewards in multiple
      contexts--effect of odor component and mixture similarity.
AB  - Discrimination among differentially rewarding flowers allows honeybees to
      maximize their foraging efficiency. We studied how honeybees are able to relate
      to differential positive rewards when the odor representations are either
      structurally dissimilar, structurally similar (or form a substrate-product duo in
      planta), or form a binary mixture sharing a common constituent. Bees were tested
      both in conditioning of the proboscis-extension response (PER) and in a free
      flying context. Our results point to honeybees using olfactory associative
      learning to differentiate between two positively rewarded odors. In PER, subjects
      discriminated best between dissimilar odors; they initially generalized between
      similar odors, but eventually learned to discriminate between them. The
      discrimination between mixtures sharing a common constituent remained poor.
      Likewise, the difference in visits to low- and high-rewarding flowers of free
      flying bees was greater for dissimilar odors than for binary mixtures sharing a
      common constituent. Consequences of the operant conditioning nature of the free
      flying context are discussed.

PMID- 14682532
TI  - Volatile emissions triggered by multiple herbivore damage: beet armyworm and
      whitefly feeding on cotton plants.
AB  - Plants are commonly attacked by more than one species of herbivore, potentially
      causing the induction of multiple, and possibly competing, plant defense systems.
      In the present paper, we determined the interaction between feeding by the phloem
      feeder silverleaf whitefly (SWF), Bemisia tabaci Gennadius (B-biotype = B.
      argentifolii Bellows and Perring), and the leaf-chewing beet armyworm (BAW),
      Spodoptera exigua Hubner, with regard to the induction of volatile compounds from
      cotton plants. Compared to undamaged control plants, infestation with SWF did not
      induce volatile emissions or affect the number and density of pigment glands that
      store volatile and nonvolatile terpenoid compounds, whereas infestation by BAW
      strongly induced plant volatile emission. When challenged by the two insect
      herbivores simultaneously, volatile emission was significantly less than for
      plants infested with only BAW. Our results suggest that tritrophic level
      interactions between cotton, BAW, and natural enemies of BAW, that are known to
      be mediated by plant volatile emissions, may be perturbed by simultaneous
      infestation by SWF. Possible mechanisms by which the presence of whiteflies may
      attenuate volatile emissions from caterpillar-damaged cotton plants are
      discussed.

PMID- 14682533
TI  - Phytochemical determination for leaf food choice by wild chimpanzees in Guinea,
      Bossou.
AB  - The feeding selection of leaves by chimpanzees was investigated from the
      perspective of phytochemistry and leaf availability. Field data were collected
      for 6 months from 1995 to 1996 and 8 months from 1997 to 1998 in Bossou, Guinea.
      Time budgets of leaf consumption by chimpanzees were analysed and the abundance
      of young leaves of each tree species for each month was estimated. Analyses of
      dried materials, stratified by leaf maturity and edibility, for the relative
      amounts of crude protein, crude fat, neutral detergent fiber, ash, and condensed
      tannin were determined. It was found that 1) leaves consumed by chimpanzees had
      higher levels of ash and lower levels of condensed tannin than leaves that were
      not eaten; 2) feeding selectivity was correlated with crude protein content; and
      3) the availability of young leaves was not correlated with the percentage of
      feeding time, neither by seasonal changes nor by tree species. Chimpanzees
      preferred leaves containing higher protein content, but did not consume leaves
      containing high condensed tannin regardless of protein content. It seems
      reasonable to consider that a different rule exists for "whether chimpanzees eat
      it or not" and "whether they prefer it or not" in phytochemical determinants of
      leaves. Some Moraceae species, which had low levels of condensed tannins, even in
      mature leaves, were an important food source for the Bossou chimpanzees.

PMID- 14682534
TI  - Effects of plant flavonoids on fecundity, survival, and feeding of the Formosan
      subterranean termite.
AB  - Fecundity, mortality, and food consumption of the Formosan subterranean termite,
      Coptotermes formosanus Shiraki, were evaluated in response to five plant
      flavonoids (genistein, biochanin A, apigenin, quercetin, and glyceollin).
      Apigenin fed at 50 microg/primary reproductive pair proved to be the most toxic
      flavonoid. Biochanin A was most effective in reducing fecundity. Subsequently,
      these two flavonoids were tested through oral feeding and topical application at
      100-microg dose. Significant reduction in the numbers of progeny was evident for
      biochanin A in both treatment methods. Choice feeding tests with termite workers
      showed that initially termites were attracted to filter paper treated with
      biochanin A, but over a period of 72 hr, consumed significantly less material
      when compared to controls. Biochanin A is a promising phytochemical with ability
      to reduce fecundity in primary reproductives of the Formosan subterranean
      termite, but it does not elicit phagostimulant activity.

PMID- 14682535
TI  - Leaf ontogeny influences leaf phenolics and the efficacy of genetically expressed
      Bacillus thuringiensis cry1A(a) d-endotoxin in hybrid poplar against gypsy moth.
AB  - We tested the hypothesis that ontogenetic variation in leaf chemistry could
      affect the efficacy of genetically expressed Bacillus thuringiensis cry1A(a) d
      endotoxin, and thus provide spatial variation in (1) foliage protection and (2)
      selective pressures that could delay the resistance of folivores. Our model
      consisted of clonal hybrid Populus plants (NC5339). Consumption of foliage and
      relative growth rates of gypsy moth, Lymantria dispar (L.) increased, and
      phenolic glycoside concentrations decreased, as leaves from transformed plants
      containing the cry1A(a) d-endotoxin and nontransformed plants matured from leaf
      plastochron index (LPI) 1-6. Feeding and growth rates were negatively correlated
      with phenolic glycosides in both transformed and nontransformed foliage. The
      presence of the B. thuringiensis d-endotoxin was at most, additive to the effect
      of the phenolic glycosides. Feeding and growth rates were positively correlated
      with condensed tannins in transformed foliage, but there was no relationship with
      condensed tannins in nontransformed foliage. The results indicate that the
      presence of foliar allelochemicals of poplar can enhance the effectiveness of
      genetically expressed B. thuringiensis d-endotoxin against gypsy moth larvae.
      However, the spatial variation in gypsy moth performance in response to the
      combination of foliar allelochemicals and d-endotoxin was not greater than the
      effect of ontogenetic variation in foliar allelochemicals alone. These results
      suggest that for this important pest, foliage protection may be obtained without
      genetically engineered defenses, and instead, by relying on ontogenetic and
      clonal variation in allelochemicals. The benefits of combining novel resistance
      mechanisms with natural ones will depend upon the specific folivore's adaptation
      to natural resistance mechanisms, such as allelochemicals. Moreover, some of the
      greatest benefits from transgenic resistance may arise from the need to protect
      trees from multiple pests, some of which may not be deterred by, or may even
      prefer, allelochemicals that confer protection from a few species.

PMID- 14682536
TI  - Are insect-synthesized retronecine esters (creatonotines) the precursors of the
      male courtship pheromone in the arctiid moth Estigmene acrea?
AB  - The pyrrolizidine alkaloid (PA) profiles were determined for adults of the
      polyphagous arctiid Estigmene acrea, which as larvae had fed on artificial diet
      supplemented with Crotalaria-pumila powder with known concentrations of PAs. The
      larvae always had a free choice between alkaloid-containing and plain diets. The
      alkaloid profiles of adults revealed a striking sexual dimorphism. Both sexes
      contained macrocyclic PAs of the monocrotaline type sequestered from the diet
      and, in addition, a substantial proportion of supinidine and retronecine esters
      synthesized by the insects from necine bases derived from the dietary alkaloids
      and necic acids of insect origin. These insect alkaloids accounted for 35% and
      55% of total PAs in males and females, respectively. The difference was that in
      females the retronecine esters (creatonotines) made up 58 microg (43% of total
      PAs), while males contained a fivefold lower proportion, 12 microg (13%). Four of
      the ten male individuals analyzed were found devoid of creatonotines. Based on
      the experimental data in combination with evidence from the literature, it is
      suggested that the creatonotines are direct pheromone precursors in E. acrea. It
      is hypothesized that this may represent a general mechanism of hydroxydanaidal
      formation from diverse macrocyclic PAs in arctiids.

PMID- 14682537
TI  - Spider mites assess predation risk by using the odor of injured conspecifics.
AB  - When a predatory mite, Amblyseius womersleyi is present, Tetranychus kanzawai
      takes refuge on its webs during a quiescent stage. To examine the factors
      responsible for the antipredator behavior of T. kanzawai, we exposed T. kanzawai
      to the odor of conspecifics, A. womersleyi, and both T. kanzawai and A.
      womersleyi. The proportion of T. kanzawai females that took refuge was
      significantly higher when they were exposed to the odor of 'both T. kanzawai and
      A. womersleyi.' Furthermore, the proportion of T. kanzawai females that took
      refuge was significantly higher when they were exposed to injured conspecifics
      than to intact conspecifics. These results suggest that T. kanzawai assesses
      predation risk, at least in part, by using the odor of injured conspecifics.

PMID- 14682538
TI  - Age and season affect chemical discrimination of Liolaemus bellii own space.
AB  - We explored chemical discrimination of own vs. novel space by different age
      classes (neonates, juveniles, and adults) of the lizard Liolaemus bellii, during
      pre- and post-hibernation seasons. We recorded the number of tongue flicks (TF)
      lizards produced during 10 min in their own or a novel enclosure. Age class and
      season affected chemical discrimination. Only adults and neonates discriminated
      their own space, albeit using different strategies: while adults made fewer TF in
      their own enclosure, neonates made more TF in their own enclosure. This
      difference was interpreted in terms of different requirements for discrimination
      of individuals during their lives. Increased chemical exploration by juveniles
      and adults at the onset of the post-hibernation season was associated with food
      searching and reproductive behaviors.

PMID- 14682539
TI  - Meeting the challenges of cattle practice in the 21st century.

PMID- 14682540
TI  - Effects of vaccination and other preventive methods for Salmonella enteritidis on
      commercial laying chicken farms.
AB  - The effect of introducing vaccinated commercial laying chickens on to farms,
      which previously had laying flocks that were infected with Salmonella
      Enteritidis, was investigated by sampling faeces and environmental samples, and
      in some cases spent hens. In 15 of 17 free-range flocks vaccination eliminated
      any evidence of infection. In 11 barn egg production flocks, vaccination produced
      similar results in four flocks on one farm but infection persisted in seven
      flocks on other farms. Vaccination of two consecutive cage layer flocks led to a
      gradual disappearance of the infection, but in 18 other flocks there was evidence
      of infection after vaccination. In one continuously occupied cage layer house,
      treatment by competitive exclusion was followed by a gradual disappearance of S
      Enteritidis in faeces and a substantial reduction in its levels in the
      environment. On four barn egg production sites disinfection with a formaldehyde,
      glutaraldehyde and quaternary ammonium compound disinfectant eliminated
      Salmonella species even though birds housed subsequently were not vaccinated. In
      three flocks that had been vaccinated for four years, S Enteritidis was still
      present. In most cases the poor performance of the vaccine was associated with
      severe rodent control problems and a poor standard of cleaning and disinfection.

PMID- 14682541
TI  - Serosurveillance of wild deer and wild boar after the epidemic of foot-and-mouth
      disease in The Netherlands in 2001.
AB  - Blood samples from 140 wild deer and 208 wild boar shot in the aftermath of the
      epidemic of foot-and-mouth disease in The Netherlands in 2001 were examined for
      antibodies to foot-and-mouth disease virus. They were all negative.

PMID- 14682542
TI  - Unusual manifestation of hepatic encephalopathy in two Irish wolfhound siblings.
AB  - In hepatic encephalopathy the brain lesions are usually characterised by
      polymicrocavitation, preferentially in the white matter, and the occurrence of
      Alzheimer type II cells. This paper describes an unusual manifestation of hepatic
      encephalopathy in two Irish wolfhound siblings in which the white matter was not
      involved predominantly. Both puppies had developed progressive neurological
      disturbances and signs of blindness. Histologically, there were widespread
      spongiform changes in the neuropil and fibre bundles interspersed within the grey
      matter, and there were some neuronal vacuoles. In both animals, the regions of
      the brain mainly affected were the nucleus caudatus, amygdala, cerebellar nuclei,
      mesencephalon, thalamus, hypothalamus and medulla oblongata. An astrogliosis
      characterised by Alzheimer type II-like cells was also observed. Electron
      microscopy revealed a splitting of the myelin sheath. No infectious agents such
      as rabies virus, canine distemper virus or prion proteins were detected. The main
      findings in the portal regions of the liver consisted of a dilatation of the
      lymphatic vessels and increased numbers of small arteries, indicating that a
      portosystemic shunt was the probable cause of the spongiform brain lesions.

PMID- 14682543
TI  - Detection of Mycoplasma ovipneumoniae in Pasteurella-vaccinated sheep flocks with
      respiratory disease in England.

PMID- 14682544
TI  - Strangulation of the small intestine in a cow by a persistent urachal remnant.

PMID- 14682545
TI  - RCVS guidance on laboratory animal medicine.

PMID- 14682546
TI  - Electric shock collars and dog training.

PMID- 14682547
TI  - Electric shock collars and dog training.

PMID- 14682548
TI  - Testing initiative for sheep ectoparasites.

PMID- 14682549
TI  - Antibiotic growth promoters.

PMID- 14682550
TI  - Shortage of radiation protection advisers.

PMID- 14682551
TI  - Is hand splinting effective for adults following stroke? A systematic review and
      methodologic critique of published research.
AB  - BACKGROUND: Upper limb hemiplegia after stroke is common and disabling. Hand
      splints are widely used to prevent contracture and reduce spasticity. OBJECTIVE:
      To assess the effectiveness of hand splinting on the hemiplegic upper extremity
      following stroke. SEARCH STRATEGY: A search was conducted of the Cochrane Central
      Register of Controlled Trials; the electronic databases MEDLINE, EMBASE, CINAHL,
      PEDro, SCI, SSCI; websites of professional associations; reference lists in trial
      reports and other relevant articles. SELECTION CRITERIA: Studies of the effect of
      upper extremity splinting on motor control, functional abilities, contracture,
      spasticity, or pain in the hand or wrist. DATA COLLECTION AND ANALYSIS: Validity
      of studies was assessed systematically and a content analysis was conducted of
      the methodologies used. Methodological quality of randomized trials was rated by
      two independent assessors using the PEDro scale. RESULTS: Nineteen studies were
      appraised for content. Of these, most (63%) were reports of case series. Four
      studies (21%) were randomized controlled trials. Methodological scores of trials
      ranged from 2 to 8 (maximum possible score 10). One trial of nominally 'medium'
      quality reported that inflatable arm splinting makes no difference to hand
      function (mean difference on Fugl-Meyer Assessment -0.12, 95% confidence interval
      (CI) -9.8 to 9.6). The remaining trials investigated effects of thermoplastic
      splints; one trial of 'high quality' reported no difference in contracture
      formation in the wrist and finger flexor muscles after wearing a hand splint
      which positioned the wrist in the traditional functional position for 12 hours
      each night for four weeks (mean difference in range of movement after four weeks
      was 1 degree, 95% CI -3.7 degrees to 6.1 degrees; power >80%). All remaining
      trials were of poor methodological quality. Limited research and lack of a no
      splint control group in all trials to date limit the usefulness of these results.
      REVIEWER'S CONCLUSION: There is insufficient evidence to either support or refute
      the effectiveness of hand splinting for adults following stroke.

PMID- 14682552
TI  - The effect of a slider shoe on hemiplegic gait.
AB  - OBJECTIVE: To assess the effect of a slider shoe on the gait speed and energy
      efficiency of hemiplegic gait. DESIGN: A-B-A single-case design to compare
      walking with and without the slider shoe. Results were assessed graphically using
      the 2SD method. SETTING: Stroke unit of an NHS general hospital in the UK.
      SUBJECTS: Four acute stroke patients undergoing gait rehabilitation.
      INTERVENTION: Walking practice with and without a slider shoe worn over the real
      shoe of the weak leg. MAIN OUTCOME MEASURES: Gait speed (10-m walk test) and
      energy efficiency (Physiological Cost Index). RESULTS: All subjects showed an
      improvement in speed and efficiency when wearing the slider shoe compared with
      the baseline phase (A1). Three subjects showed a sustained improvement in
      efficiency and two showed a sustained improvement in speed in the second baseline
      phase (A2). CONCLUSION: A slider shoe may improve the speed and efficiency of
      hemiplegic gait for people in the early stages of gait rehabilitation. Further
      investigation is warranted.

PMID- 14682553
TI  - Assessment of the perceptual threshold of touch (PTT) with high-frequency
      transcutaneous electric nerve stimulation (Hf/TENS) in elderly patients with
      stroke: a reliability study.
AB  - OBJECTIVE: To evaluate the inter-rater reliability and reliability between
      occasions of assessing the perceptual threshold of touch (PTT) with high
      frequency transcutaneous electric nerve stimulation (Hf/TENS) in elderly patients
      with stroke. DESIGN: A test-retest study of reliability using intraclass
      correlation coefficient (ICC) and limits of agreement. SETTING: Geriatric
      rehabilitation unit. SUBJECTS: Thirty-two consecutive patients with stroke > or =
      65 years of age. MAIN OUTCOME MEASURES: Two-channel current stimulator TENS CEFAR
      Tempo with four self-adhesive skin electrodes. The stimulator delivered a high
      frequency constant current of 40 Hz. The strength of the stimulation was
      quantifiable and assessed in milliampere (mA). INTERVENTIONS: The assessments
      were performed on the hands and feet by two raters. The PTT was identified as the
      level registered in milliampere (mA) at which the patients perceived a tingling
      sensation. RESULTS: The ICC values (0.94-0.99) were shown to be good for inter
      rater reliability, as well as reliability between occasions. However an
      additional analysis with limits of agreement showed a high level of agreement for
      assessment of the hand but a moderate to low agreement for assessment of the foot
      where some bias was also identified. Clinical acceptable reliability: > or = 1 mA
      for the hand and > or = 5 mA for the foot are so far recommended for establishing
      real differences in clinical measures. CONCLUSION: Hf/TENS shows an overall high
      reliability for assessing the PTT of the hand and moderate to low reliability for
      the foot. Additional research with exclusion of bias is needed to determine the
      reliability of assessing the foot.

PMID- 14682554
TI  - Reliability and validity of a postal version of the Reintegration to Normal
      Living Index, modified for use with stroke patients.
AB  - OBJECTIVE: To adapt the Reintegration to Normal Living Index (RNLI) for postal
      use with stroke patients. DESIGN: Reliability was examined using test-retest on
      26 stroke patients. Construct validity was tested on 76 patients by examining
      correlations between the modified RNLI and related scales. SUBJECTS: Patients at
      three months to one year post stroke. RESULTS: All items demonstrated better than
      chance agreement between test and retest and seven items substantial agreement
      (kappa = >0.61). The modified RNLI correlated positively with related scales.
      Patients with stronger reintegration to normal living had better outcomes in
      anxiety, depression, daily activity and quality of life. CONCLUSION: This postal
      instrument appears reliable and valid and may be a useful outcome measure in
      stroke studies.

PMID- 14682555
TI  - The validity of questionnaire measures for assessing depression after stroke.
AB  - OBJECTIVE: Depression has been reported to occur frequently after stroke. The aim
      of the study was to assess the validity of questionnaire measures for screening
      for depression after stroke. DESIGN: Cross-sectional correlational study between
      questionnaire measures of mood and psychiatric interview. SETTING: Hospital and
      community. PARTICIPANTS: Stroke patients were recruited from hospital wards and
      from a randomized controlled trial of cognitive behavioural therapy. MAIN
      MEASURES: Beck Depression Inventory, Wakefield Depression Inventory, General
      Health Questionnaire 28 and Schedules for Clinical Assessment in Neuropsychiatry.
      RESULTS: Poor agreement was found between psychiatric diagnosis and questionnaire
      measures of mood. The sensitivity of the questionnaire measures was high, but
      specificity was low. No cut-off points with satisfactory sensitivity and
      specificity could be identified from ROC curves. CONCLUSIONS: Although
      questionnaire assessments of depression provide a satisfactory screening method,
      specificity values are too low to provide a basis for the diagnosis of
      depression. Measures need to be developed with higher specificity to facilitate
      screening for depression after stroke.

PMID- 14682556
TI  - Assessing mood in patients with multiple sclerosis.
AB  - OBJECTIVE: To assess the validity and reliability of mood measures for use with
      people with multiple sclerosis (MS). DESIGN: Four mood measures designed for use
      with people with communication and cognitive problems were completed; two were
      completed with the patient at interview and two by hospital staff or carers of
      the patients. This procedure was repeated two weeks later to assess test-retest
      reliability. SUBJECTS: People with MS at a rehabilitation unit (n = 22) and
      living in the community (n = 27). MAIN OUTCOME MEASURES: The Stroke Aphasic
      Depression Questionnaire (SADQ) and Signs of Depression Scale (SODS) were
      completed by rehabilitation unit staff or by carers of the patients. An assistant
      psychologist completed the Visual Analogue Self-Esteem Scale (VASES) and the
      Visual Analogue Mood Scales (VAMS) with each patient. The Guy's Neurological
      Disability Scale (GNDS) was administered to assess physical disability.
      Nonprofessional carers were asked to complete the General Health Questionnaire 12
      (GHQ-12) about themselves. RESULTS: In both samples there were significant
      correlations between scores on the two self-report measures (VASES and VAMS)
      (r(s) = 0.51-0.79) and between scores on the two observational measures (SADQ and
      SODS) (r(s) = 0.62-0.81) but not between the observational and self-report
      measures. There was a significant correlation between the SODS and the carer GHQ
      (r(s) = 0.68, p < 0.01), indicating that carer mood influenced reporting of
      patients' mood. There was no significant influence of profession on the
      observational measures, indicating good inter-rater reliability. Test-retest
      reliability was high for patients in the community but not for patients in
      hospital. CONCLUSIONS: In both the inpatient and community samples, the self
      report and observational mood measures appeared to be measuring different aspects
      of patients' mood. Further investigation is needed to determine which of these is
      providing the most accurate information.

PMID- 14682557
TI  - A post-discharge quality of life outcome measure for lower limb amputees: test
      retest reliability and construct validity.
AB  - OBJECTIVE: To adapt the Patient Generated Index (PGI) quality of life measure for
      use with lower limb amputees and to conduct a test-retest reliability and
      construct validity study on the adapted measure. DESIGN: Repeat questionnaire
      interviews with a four-week interval administered by trained peers. SETTING:
      Participants' homes. SUBJECTS: Forty-two unilateral lower limb transfemoral
      amputees, 16 years of age or older and fluent in English, fitted with a
      prosthesis and discharged into the community for at least one year following
      postoperative rehabilitation therapy. MAIN RESULTS: An intraclass correlation
      coefficient of 0.48 (p < 0.001) was achieved for the index reliability analyses.
      Intraclass correlation (ICC) values for the seven most commonly mentioned areas
      of life affected by the amputation and its treatment ranged from 0.40 to 0.92.
      Comparing the PGI with the SF-12 Health Survey physical and mental component
      summaries gave Pearson's correlation coefficients of 0.12 (p < 0.5) and 0.56 (p <
      0.001) respectively. Multiple linear regression analysis showed the SF-12
      physical and mental component scores explained 31.5% of the variability in PGI
      scores, however, the mental component scores alone explained 31.2%. CONCLUSIONS:
      The PGI was adapted and found to be moderately reliable in terms of repeatability
      during successive follow-up interviews. Testing its construct validity supported
      a stronger relationship between mental health and quality of life than between
      physical health and quality of life.

PMID- 14682558
TI  - Defining and using quality of life: a survey of health care professionals.
AB  - OBJECTIVE: 'Quality of life' is an important but poorly defined outcome in health
      and health care research. We sought to identify stroke professionals' definitions
      of quality of life and views of the purpose of its assessment. DESIGN: Using
      issues identified during in-depth interviews with stroke care professionals, we
      designed a postal survey questionnaire. Participants were asked to define quality
      of life, identify the purposes of assessing it and report experiences of
      measuring patient quality of life. Comparisons between professional groups were
      analysed using chi-squared tests of significance. SUBJECTS: Care of the elderly
      physicians, physiotherapists and occupational therapists in the UK. RESULTS: Of
      2793 questionnaires distributed, 1572 were returned (56% response rate). Quality
      of life was defined in terms of 'happiness' by 72%; 25% included social well
      being; 25% included physical abilities. Most (91%) identified 'asking patients'
      as an effective way to assess quality of life; 40% using standardized measures.
      Half those who reported using quality of life measures experienced difficulties,
      including being unsure about which measure to use and concerns about validity.
      CONCLUSIONS: The idea of quality of life as happiness dominated responders'
      definitions. We argue that the term may be used in both a technical sense (an
      outcome) and in a broad colloquial sense, without necessarily distinguishing
      between the two. Clarification of the concept and its uses is required if recent
      calls to introduce quality of life assessment in clinical care are to be
      feasible.

PMID- 14682559
TI  - Effects of knee joint angle and tilt table incline on force distribution at the
      feet and supporting straps.
AB  - OBJECTIVE: To investigate the effects of tilt table incline and knee flexion
      angle on the degree of weight bearing and forces exerted across the supporting
      straps. DESIGN: A quantitative and exploratory study to investigate the effects
      of a mechanical procedure. SETTING: Physiotherapy gymnasium. SUBJECTS: Twelve
      healthy subjects (9 female, 3 male) aged 22-45 years. INTERVENTIONS: Subjects
      stood on a tilt table, on two occasions, with simulated contractures of 10
      degrees and 40 degrees knee flexion. Nine tilt angles, between 10 degrees and 90
      degrees, were maintained for 1 minute each in random order. MAIN OUTCOME
      MEASURES: Force was recorded from single-point load cells placed under the feet,
      and at knee and chest straps. RESULTS: The degree of simulated knee contracture
      (10 degrees or 40 degrees) influenced the distribution of forces at different
      recording sites. Weight bearing increased with table incline and was
      significantly less with the 40 degrees than the 10 degrees knee angle (p <
      0.001). Conversely, forces across the knee straps were systemically higher with
      the 40 degrees knee angle (p < 0.0001). The effects were accentuated by greater
      body weight. Forces across the chest strap also increased with tilt and were
      significantly larger with the 40 degrees knee angle (p < 0.05). CONCLUSIONS: The
      relationships between table incline, angle of knee flexion and distribution of
      forces generated during tilt table standing have been quantified and described.
      Standing with flexed knees involved less weight bearing under the feet and
      greater force exerted across the supporting straps. These effects were more
      pronounced at the higher knee angle and with greater body weight, and could be
      modified by reducing table incline.

PMID- 14682560
TI  - Prevalence of pressure sores in a community sample of spinal injury patients.
AB  - OBJECTIVES: To estimate the point prevalence of pressure sores in a community
      sample of spinal cord injured patients who were followed up by a spinal injuries
      unit and to evaluate whether self-management strategies were associated with
      decreased risk of pressure sores. SETTING: A regional spinal injuries unit, UK.
      DESIGN: Postal questionnaire survey. MAIN OUTCOME MEASURE: Presence of pressure
      sores. SUBJECTS: All patients who were being followed up on a regular basis by
      the unit. RESULTS: Out of 760, 520 replied to the questionnaire; 472 were
      eligible for analysis. Point prevalence of pressure sores was 23% (99). Failure
      to inspect the skin daily for pressure damage was associated with decreased
      prevalence of pressure sores (odds ratio (OR) 0.5; 95% confidence interval (CI)
      0.2-0.83). Those who inspected their skin daily, however, had a higher proportion
      of stage I pressure sores, but this was not statistically significant. Smoking
      (OR 1.8; 95% CI 1-3.3) and pre-existing medical problems (OR 1.8; 95% CI 1-3)
      were associated with increased prevalence of pressure sores. Regular lifting of
      weight at least once in an hour while seated, age, gender, neurological level,
      employment status, living alone and faecal and urinary incontinence were not
      significant predictors of pressure sores. CONCLUSIONS: Nearly one-quarter of
      participants had pressure sores at the time of the survey. Periodic weight lifts
      and daily inspection of skin for pressure damage were not associated with
      decreased prevalence of pressure sores in this sample. However, those who
      inspected skin daily tended to detect pressure damage early.

PMID- 14682561
TI  - Muscle strength in patients with chronic pain.
AB  - OBJECTIVE: To analyse the influence of chronic pain on muscle strength. DESIGN:
      Muscle strength of patients with unilateral nonspecific chronic pain, in an upper
      or lower limb, were measured according to a standardized protocol using a hand
      held dynamometer. Before and after muscle strength measurement, a visual analogue
      scale for pain intensity was assessed. RESULTS: Forty patients were measured and
      the muscle strength of the painful side was 20-30% less than that of the
      nonpainful side. Strength reduction was seen in the whole limb. A significant
      correlation between pain intensity and reduced muscle strength in the painful
      limb existed for hip flexion, knee flexion, knee extension and three-point grip.
      CONCLUSIONS: A strength reduction of 20-30% in a painful limb seems to be
      'normal' in chronic pain patients.

PMID- 14682562
TI  - Post-discharge nursing problems of spinal cord injured patients: on which fields
      can nurses contribute to rehabilitation?
AB  - OBJECTIVE: To identify nursing problems of spinal cord injured (SCI) patients
      after discharge from clinical rehabilitation and to identify gaps in the nursing
      care regarding the prevention of these problems. DESIGN: The study had an
      exploratory character and was divided into three phases. Phase 1 had a
      qualitative nature. Eight patients were interviewed to obtain insight into
      experienced problems after discharge. In phase 2, a panel of experts regarding
      nursing care for SCI patients selected nursing problems out of all problems
      mentioned. Phase 3 consisted of a mailed questionnaire including the nursing
      problem areas identified in phase 2, which was sent to all patients that were
      discharged during the last 18 months before the study. SETTING: Specialist
      rehabilitation centre, The Netherlands. SUBJECTS: Eight patients participated in
      phase 1 (100% response rate), 35 nurses participated in phase 2 (87.5% response
      rate) and 35 patients participated in phase 3 (62.5% response rate). RESULTS: The
      most important nursing problems in the response group appeared to be: limitations
      to activities of daily living, having difficulties in asking for help
      (assertiveness), pain, coping with the disability, dependency on personal help
      and problems with changed bladder regulation. The respondents made several
      suggestions for improving nursing care, involving both clinical care and care
      after discharge. CONCLUSIONS: SCI patients experience serious problems after
      discharge from clinical rehabilitation. Nurses can give input on a wide variety
      of these problems.

PMID- 14682563
TI  - Falls in community-dwelling older persons followinig hip fracture: impact on self
      efficacy, balance and handicap.
AB  - OBJECTIVE: To compare the four-month outcomes of fallers and nonfallers as well
      as those with slow gait speed in patients with hip fracture successfully
      discharged back to the community. DESIGN: Prospective study with four-month
      follow-up data. SETTING: Community sample of survivors of hip fracture who have
      completed their rehabilitation programme. SUBJECTS: A consecutive sample of 73
      community-dwelling, cognitively intact older adults admitted to hospital
      following a fall-related hip fracture and available to complete a follow-up
      assessment at four months. MAIN OUTCOME MEASURES: At baseline, data collection
      consisted of the Modified Barthel Index (MBI), Mini Mental State Examination
      (MMSE), sociodemographics and medical history. At four months follow-up, data
      collection consisted of the MBI, London Handicap Scale (LHS), Berg Balance Scale
      (BBS), a 10-metre timed walk test, Falls Efficacy Scale (FES) and the Activities
      Balance Confidence (ABC) scale. Participants were also asked to recall if they
      had fallen in the four months since their fracture. RESULTS: Seventy-three
      participants had complete data for evaluation. There was minimal disability with
      a mean MBI of 91.2 but there was some residual handicap with a mean LHS of 0.67.
      Those who had fallen had lower self-efficacy (FES) and greater handicap (LHS).
      Those with slower gait speed were more handicapped (LHS), had lower self-efficacy
      (FES and ABC) and lower balance scores (BBS). CONCLUSIONS: Measuring ADL
      disability alone loses valuable information in community-dwelling survivors of
      hip fracture. Falls after hip fracture should be a target for treatment and our
      data give some weight to the idea of a fall fracture cycle. Gait speed, which may
      reflect lower limb strength, is also a target for therapeutic interventions.
      These measures should be included in clinical practice.

PMID- 14682564
TI  - Nitrogen fixation in the activated sludge treatment of thermomechanical pulping
      wastewater: effect of dissolved oxygen.
AB  - N-ViroTech, a novel technology which selects for nitrogen-fixing bacteria as the
      bacteria primarily responsible for carbon removal, has been developed to treat
      nutrient limited wastewaters to a high quality without the addition of nitrogen,
      and only minimal addition of phosphorus. Selection of the operating dissolved
      oxygen level to maximise nitrogen fixation forms a key component of the
      technology. Pilot scale activated sludge treatment of a thermomechanical pulping
      wastewater was carried out in nitrogen-fixing mode over a 15 month period. The
      effect of dissolved oxygen was studied at three levels: 14% (Phase 1), 5% (Phase
      2) and 30% (Phase 3). The plant was operated at an organic loading of 0.7-1.1 kg
      BOD5/m3/d, a solids retention time of approximately 10 d, a hydraulic retention
      time of 1.4 d and a F:M ratio of 0.17-0.23 mg BOD5/mg VSS/d. Treatment
      performance was very stable over the three dissolved oxygen operating levels. The
      plant achieved 94-96% BOD removal, 82-87% total COD removal, 79-87% soluble COD
      removal, and >99% total extractives removal. The lowest organic carbon removals
      were observed during operation at 30% DO but were more likely to be due to
      phosphorus limitation than operation at high dissolved oxygen, as there was a
      significant decrease in phosphorus entering the plant during Phase 3. Discharge
      of dissolved nitrogen, ammonium and oxidised nitrogen were consistently low (1.1
      1.6 mg/L DKN, 0.1-0.2 mg/L NH4+-N and 0.0 mg/L oxidised nitrogen). Discharge of
      dissolved phosphorus was 2.8 mg/L, 0.1 mg/L and 0.6 mg/L DRP in Phases 1, 2 and 3
      respectively. It was postulated that a population of polyphosphate accumulating
      bacteria developed during Phase 1. Operation at low dissolved oxygen during Phase
      2 appeared to promote biological phosphorus uptake which may have been affected
      by raising the dissolved oxygen to 30% in Phase 3. Total nitrogen and phosphorus
      discharge was dependent on efficient secondary clarification, and improved over
      the course of the study as suspended solids discharge improved. Nitrogen fixation
      was demonstrated throughout the study using an acetylene reduction assay. Based
      on nitrogen balances around the plant, there was a 55, 354 and 98% increase in
      nitrogen during Phases 1, 2 and 3 respectively. There was a significant decrease
      in phosphorus between Phases 1 and 2, and Phase 3 of the study, as well as a
      significant increase in nitrogen between Phases 2 and 3 which masked the effect
      of changing the dissolved oxygen. Operation at low dissolved oxygen appeared to
      confer a competitive advantage to the nitrogen-fixing bacteria.

PMID- 14682565
TI  - Nitrogen removal from digester supernatant via nitrite--SBR or SHARON?
AB  - Separate biological elimination of nitrogen from the digester supernatant of a
      municipal wastewater treatment plant (WWTP) was investigated in pilot and full
      scale plants. Denitrification mainly via nitrite was achieved in a sequencing
      batch reactor (SBR) and a continuous flow reactor (CSTR or SHARON). Suppression
      of nitrite oxidation in the SBR was feasible at short aerobic/anaerobic intervals
      allowing for immediate denitrification of the produced nitrite. Nitrate
      production could also be stopped by exposing the biomass to anaerobic conditions
      for 11 days. Temporarily high concentrations (up to 80 gNH3-Nm(-3)) of free
      ammonia could not be considered as the major reason for inhibiting nitrite
      oxidation. In a full-scale SBR plant 90% of the nitrogen load was denitrified in
      a total hydraulic retention time (HRT) of 1.6 days and with a sludge age between
      15 and 20 days. Ethanol and methanol were used for denitrification. The specific
      average substrate consumption was 2.2 gCOD(dosed) g(-1)N(removed) with an
      effective biomass yield of 0.2 gCOD(biomass) g(-1)COD(dosed). No dosing with base
      was required. In the SHARON process full nitrogen elimination was achieved only
      with a total HRT greater than 4 days at 29 degrees C. The overall costs were
      estimated at 1.4 euros kg(-1)N(removed) for the SBR and 1.63 euros kg(
      1)N(removed) in SHARON mode, respectively. The SHARON process is simple in
      operation (CSTR) but the tank volume has to be significantly greater than in SBR.

PMID- 14682566
TI  - Advanced nitrogen elimination by encapsulated nitrifiers.
AB  - By introducing a mixed population of nitrifiers encapsulated in gel lens beads a
      more selective nitrification process was found in treatment of settled sewage in
      lab scale at a hydraulic retention time (HRT) of about 30 to 60 minutes. The
      reaction rates for oxidation of soluble chemical oxygen demand (SCOD) were found
      to vary between 25 to 150 mg/L x h while nitrification takes place around 50 mg
      nitrogen per hour and litre reaction volume. However, based on this SCOD removal
      in the nitrification step, a consequent post-denitrification process without
      nitrate recycle and dosage of external carbon sources has been proven to reach
      substantial nitrate elimination of up to 20 mg nitrogen per litre at COD/N-ratios
      of approx. 6 in settled sewage. At such COD/N-ratios, suitable nitrogen
      elimination seems to be possible, because the bioflocs of settled sewage,
      produced so far by SCOD oxidation and entrapment of particulate COD, are passing
      through the nitrification process having a substantial contribution to the
      denitrification rate additionally to the remaining SCOD.

PMID- 14682567
TI  - Biological nitrification and denitrification of opto-electronic industrial
      wastewater.
AB  - Development and application of biological nutrient removal processes accelerated
      significantly over the past decade due to more stringent nutrients (nitrogen and
      phosphorus) discharge limits being imposed on wastewater treatment plants. The
      opto-electronic industry has developed very fast over the past decade in the
      world. The wastewater often contains a significant quantity of organic nitrogen
      compounds and has a ratio of over 95% in organic nitrogen (Org-N) to total
      nitrogen (T-N). In this study, a 2-stage Anoxic/Aerobic pre-denitrification
      process was established and the efficiency of wastewater treatment was evaluated.
      Wastewater from an actual LCD-plant was obtained as the sample for looking into
      the feasibility of opto-electronic industrial wastewater treatment. Hydraulic
      retention time (HRT) and mixed liquor recycle rate (MLR) were controlled
      independently to distinguish between the effects of these two factors. Under
      suitable HRT and mixed liquor recycle ratio, effluents of NH4-N, NOx-N and COD
      can fall below 20 mg/l, 30 mg/l and 80 mg/l.

PMID- 14682568
TI  - Long term effects of temperature and substrate level on BNR with an external
      nitrification reactor.
AB  - This study was conducted with a BNR (biological nutrient removal) process with an
      external nitrification and switching arrangement of anoxic and oxic stages. It
      was observed that the SPRR (specific phosphorus release rate) and SDNR (specific
      denitrification rate) were greatly affected by the organic loads, and SDNR had a
      higher temperature effect than other kinetic rates including nitrification. It
      was further observed that the stoichiometric values like PHA (poly
      hydroxyalkanoate) stored for P release and PHA consumed for P uptake also varied.
      Variations of % Px (phosphorus content) and PHA as intracellular matter suggest
      the PAOs were more active at lower temperatures with this process configuration,
      where more than 70% of NH4-N and phosphorus were removed at temperatures below 10
      degrees.

PMID- 14682569
TI  - Biological phosphorus removal from a phosphorus-rich dairy processing wastewater.
AB  - Dairy industry processing wastewaters consist mainly of dilutions of milk, milk
      products and cleaning solutions and, depending on the processes used, may be rich
      in phosphorus. In New Zealand and internationally, chemical removal of phosphorus
      is typically the phosphorus removal method of choice from dairy processing
      wastewaters. The enhanced biological phosphorus removal (EBPR) process was
      investigated in this study as an alternative phosphorus removal option using a
      continuous activated sludge system. A synthetic dairy processing wastewater was
      firstly subjected to fermentation in an anaerobic reactor (HRT = 12 hrs, pH =
      6.5, temperature = 35 degrees C) resulting in a fermented wastewater with an
      average volatile fatty acid (VFA) concentration of 1055 mg COD/L. The activated
      sludge reactor was operated in an AO configuration with an HRT of 2.5 days and an
      SRT of 15 days. Stable EBPR was exhibited with 42 mg P/L removed, resulting in a
      final sludge phosphorus content of 4.9% mg P/mg TSS. In the anaerobic zone (HRT =
      2.85 hrs) the sludge had a phosphorus content of 3.16% mg P/mg TSS and a poly
      beta-hydroxyalkanoate (PHA) concentration of 86 mg COD/g TS.

PMID- 14682570
TI  - Characterisation of aerobic bio treatment of meat plant effluent.
AB  - Primary treated meat processing plant effluent was characterised for the
      calibration of the ASM 2 model. The total COD of the wastewater was 500-2,000 mg
      L(-1). The wastewater contained 15-18% of RBCOD. RBCOD of the meat processing
      wastewater was from short chain fatty acids (SCFA). Acetic and iso-valeric acids
      contributed 50% of the total SCFA COD. The inert soluble and particulate COD
      fractions were each 4%. The COD exerted by carbohydrate was 5% of the total COD.
      Fat and protein contributed 51% and 44% of the total COD of the wastewater
      respectively. The average concentrations of ammonia, total phosphorus, total
      suspended solids and alkalinity were 75 mg L(-1), 34 mg L(-1), 450 mg L(-1) and
      275 mg L(-1) CaCO3 respectively. Maximum specific growth rates of heterotrophs
      and autotrophs were between 1.2-2.5 day(-1) and 0.65-0.8 day(-1). The
      heterotrophs yield coefficient was 0.63 on a COD basis.

PMID- 14682571
TI  - Respirometric measurement of kinetic parameters: effect of activated sludge floc
      size.
AB  - The variation of activated sludge floc size with the mixing intensity of a
      mechanically stirred respirometer, expressed in terms of the mean energy
      dissipation rate, was characterized using a photometric dispersion analyzer. The
      floc size decreased rapidly when the energy dissipation rate was increased from
      1.33 x 10(-3) to 2.68 x 10(-3) W/kg. Experiments were performed to investigate
      the effect of floc size on the oxygen saturation coefficient measured under the
      condition of acetate oxidation. The respirometric data were interpreted by
      considering only the kinetics of biochemical reactions. The variation of the
      oxygen saturation coefficient with mixing intensity was found to correlate with
      the variation of floc size with mixing intensity. The oxygen saturation
      coefficient was found to decrease from 0.23 to 0.08 mg/L when the mean energy
      dissipation rate was increased from 1.33 x 10(-3) to 2.68 x 10(-3) W/kg. The
      dependence of the oxygen saturation coefficient on floc size or mixing intensity
      suggests the presence of mass transfer resistances in large flocs.

PMID- 14682572
TI  - Airlift-reactor design and test for aerobic environmental bioprocesses with
      extremely high solid contents at high temperatures.
AB  - Bioprocesses at high temperatures gained considerably in importance within the
      last years and several new applications for aerobic, extreme thermophilic
      environmental bioprocesses are emerging. However, this development is not yet
      matched by adequate bioreactor designs, especially if it comes to the treatment
      of solids. In this communication we propose the use of airlift reactors to bridge
      this gap. The design of an internal draught tube bioreactor
      (Area(Riser)/Area(Downcomer) . 1; Height/Diameter . 8) is described in detail.
      The influence of the temperature on gas hold-up, liquid velocity and mixing
      characteristics was investigated. It was shown that this reactor could hold up to
      1 t quartz sand per m3 in suspension at moderate aeration rates. Despite the
      decreasing oxygen solubility, the oxygen transfer rate increased with rising
      temperature due to the improved mass transfer parameters. With rising solid
      content, the oxygen transfer rate increased and reached a maximum at a solid
      content of about 140 kg m(-3) before it decreased again. However, it is only
      slightly reduced at the highest solid contents. The results demonstrate that
      aerobic bioprocesses at high temperatures are not only feasible, but can be very
      efficient if carried out in proper bioreactors.

PMID- 14682573
TI  - Microbial activity of biofilm during start-up period of anaerobic hybrid reactor
      at low and high upflow feeding velocity.
AB  - With an aim to shorten start-up time of an Anaerobic Hybrid Reactor (AHR),
      initial biofilm development was studied, particularly at different upflow feeding
      velocities. At a low (0.01 m x h(-1)) upflow velocity, initial biofilm was found
      to develop via the attachment of suspended biomass in the packed zone, while
      microbial growth on the film was insignificant. Contrarily, with higher (1.0 m x
      h(-1)) upflow velocity, initial biofilm development was from both microbial
      attachment and growth on supporting media. Biofilm thickness was determined using
      confocal laser scanning microscopy (CLSM), which indicated that the biofilm
      developed faster with the higher velocity, due to the contribution of the
      microbial growth on supporting media. When operated beyond the initial biofilm
      development with the lower velocity, both the activity of acetogens and the
      methanogens increased, although there was a lower amount of attached biomass on
      the supporting media. Whereas, both groups were found to decrease with higher
      upflow velocity, but acidogenic activity increased. It can be concluded that
      higher upflow velocity positively affected the initial stage of biofilm
      development and has the potential to accelerate attached biomass on supporting
      media during the initial phase. Subsequently, the upflow velocity should be
      reduced to the normal rate to enhance the methanogenic activity.

PMID- 14682574
TI  - Biomass accumulation patterns for removing volatile organic compounds in rotating
      drum biofilters.
AB  - A rotating drum biofilter (RDB) with multi-layered foam media was developed for
      the improvement of current biofiltration technology. The biofilter was used to
      investigate the effects of organic loadings and influent volatile organic
      compound (VOC) concentrations on VOC removal efficiency and biomass accumulation.
      These effects were evaluated using diethyl ether and toluene separately as model
      VOCs at an empty bed contact time (EBCT) of 30 s. When the toluene loading
      increased from 2.0 to 4.0 and 8.0 kgCOD m(-3) day(-1), toluene removal efficiency
      of the biofilter decreased from over 99% to 78% and 74%, respectively. The
      biomass distribution was found to be more even within the medium when removing
      toluene than when removing diethyl ether. Higher organic loading also resulted in
      the more even distribution of the biomass. The ratios of biomass accumulation
      rates in the medium of the outermost, middle and innermost layers ranged from
      1:0.11:0.02 when removing diethyl ether at 2.0 kgCOD m(-3) day(-1) to 1:0.69:0.51
      when removing toluene at 8.0 kgCOD m(-3) day(-1). Review of these ratios revealed
      three biomass accumulation patterns: surface pattern, in-depth pattern and
      shallow pattern. Different patterns represent different removal mechanisms in the
      biofiltration process. Improved biofilter design and operation should be based on
      the biomass accumulation pattern.

PMID- 14682575
TI  - Laboratory scale and pilot plant study on treatment of toxic wastewater from the
      petrochemical industry by UASB reactors.
AB  - This research concentrates on the development of an integrated approach to
      evaluate the possibility of treating very concentrated (COD = 15-20 g/l) and
      toxic wastewater (nitro-organic effluent) from the petrochemical industry in UASB
      reactors. A newly developed method utilising a modified Micro-Oxymax respirometer
      was used to (1) evaluate the inhibitory effects of varying concentrations of
      nitro-organic effluent on anaerobic granular sludge and (2) to make the proposal
      of operational parameters for the start up of the continuous process.
      Subsequently, the continuous tests were undertaken using laboratory scale upflow
      anaerobic sludge bed reactors to test gradual adaptation of anaerobic biomass to
      nitro-organic effluent. Practical application of the experimental results of the
      laboratory-scale continuous tests was evaluated by running the UASB pilot plant.
      Acceptable COD removal efficiencies were obtained when nitro-organic effluent was
      diluted with a readily biodegradable substrate up to 80 vol % of nitro-organic
      effluent in the inlet. The COD removal was 90% and the methane production rate
      was 4.5 l/d. Wastewater was detoxified and no acute toxicity of the treated
      wastewater to the anaerobic biomass was detected. This research indicates that
      anaerobic digestion of the undiluted nitro-organic effluent was not feasible.
      However, it is possible to blend the nitro-organic effluent with another effluent
      stream and co-treat these effluents.

PMID- 14682576
TI  - Membrane bioreactors for final treatment of wastewater.
AB  - The full-scale existing treatment plant in a paper mill in Hedera, Israel,
      includes equalization, solids separation by either straining or by dissolved air
      flotation and biological treatment by activated sludge. The operation of the
      existing biological process is often characterized by disturbances, mainly bad
      settling, voluminous bioflocs, followed by wash-out of the biosolids. This paper
      summarizes the results obtained in a study based on a pilot plant including a
      membrane biological reactor (MBR) compared to the "conventional" activated sludge
      process in the aerobic treatment of the effluent obtained from an anaerobic
      reactor. During the pilot operation period (about 90 days after achieving steady
      state) the MBR system provided steady operation performance, while the activated
      sludge produced effluent characterized by oscillatory values. The results are
      based on average values and indicate much lower levels of suspended solids in the
      MBR effluent, 2.5 mg/L, as compared to 37 mg/L in the activated sludge. As a
      result, the total organic mater content was also substantially lower in the MBR
      effluent, 129 vs 204 mg/L as COD, and 7.1 vs 83 mg/L as BOD. The MBR enabled
      better nitrification. The ability to develop and maintain a concentration of over
      11,000 mg/L of mixed liquor volatile suspended solids in the MBR bioreactor
      enabled an intensive bioprocess at relatively high cell residence time. As a
      result the biosolids which had to be removed as excess sludge were characterized
      by relatively low volatile/total suspended solids ratio, around 0.78. This could
      facilitate and lower the cost of biosolids treatment and handling. The results of
      this comparative study indicate that in the case of MBR there will be no need for
      further treatment, while after activated sludge additional filtration will be
      required. The study leads to the conclusion that MBR will be the best technology
      for aerobic treatment of the anaerobic effluent of the paper mill.

PMID- 14682577
TI  - Hazardous waste landfill leachate treatment using an activated sludge-membrane
      system.
AB  - This research was aimed to investigate the capability of a combined system of
      activated sludge and microfiltration processes with backflushing technique to
      reduce organic carbon and nitrogen compounds in hazardous landfill leachates. The
      experiments included acclimation, batch and continuous processes. The continuous
      process was conducted with a 24 hour HRT (Hydraulic Retention Time), and the SRT
      (Solid Retention Time) ranged from 16 to 36 days. The aeration basin volume was 5
      L and the membrane filter used was a hollow fiber module made from polypropylene
      with pore size of 0.2 microm. The batch process (without membrane separation)
      achieved its steady state condition over a period of 33 days. The removal of COD,
      BOD5 and ammonia-N were 52.5%, 94.3% and 75.5%, respectively. The kinetic
      parameters obtained are as followed: the maximum specific growth rate constant
      (microm): 0.96/day and the saturation substrate constant (Ks): 16,445.32 mg/L.
      The high value of Ks indicated that the leachate was not easily biodegraded. The
      continuous process revealed that the system with SRT of 32 days was more stable
      than that of 16 and 24 days. The reduction of COD, BOD5 and ammonia-N were 31.3%;
      66% and 98%, respectively. The stable flux was achieved around 5 L/m2 x hour.

PMID- 14682578
TI  - Molecular assessment of ammonia- and nitrite-oxidizing bacteria in full-scale
      activated sludge wastewater treatment plants.
AB  - Nitrification was assessed in two full-scale wastewater treatment plants (WWTPs)
      over time using molecular methods. Both WWTPs employed a complete-mix suspended
      growth, aerobic activated sludge process (with biomass recycle) for combined
      carbon and nitrogen treatment. However, one facility treated primarily municipal
      wastewater while the other only industrial wastewater. Real time PCR assays were
      developed to determine copy numbers for total 16S rDNA (a measure of biomass
      content), the amoA gene (a measure of ammonia-oxidizers), and the Nitrospira 16S
      rDNA gene (a measure of nitrite-oxidizers) in mixed liquor samples. In both the
      municipal and industrial WWTP samples, total 16S rDNA values were approximately 2
      9 x 10(13) copies/L and Nitrospira 16S rDNA values were 2-4 x 10(10) copies/L.
      amoA gene concentrations averaged 1.73 x 10(9) copies/L (municipal) and 1.06 x
      10(10) copies/L (industrial), however, assays for two distinct ammonia oxidizing
      bacteria were required.

PMID- 14682579
TI  - Evaluation of biomass production in unleaded gasoline and BTEX-fed batch
      reactors.
AB  - BTEX removal under aerobic conditions by unleaded gasoline acclimated biomass and
      BTEX acclimated biomass, and the effect of surfactant on BTEX biodegradation were
      evaluated. The effect of BTEX concentration as the sole source of carbon for
      biomass acclimation and the effect of yeast extract on cell growth in unleaded
      gasoline-fed reactors were also evaluated. For the unleaded gasoline acclimated
      biomass, benzene was shown the most recalcitrant among all BTEX, followed by o
      xylene and toluene with 16-23%, 35-41% and 57-69% biodegradation, respectively.
      Ethylbenzene was consistently the fastest BTEX chemical removed with 99%
      biodegradation for the four bioreactor acclimated biomasses tested. For the 1,200
      ppm BTEX acclimated biomass, benzene showed the highest removal efficiency (99%)
      among the four biomass environmental conditions tested, along with 99% toluene
      and 99% ethylbenzene biodegradation. O-xylene showed 92-94% removal. In all
      bioassays tested Tergitol NP-10 was fully removed, and did not have a substantial
      effect on BTEX biodegradation at the end of a 10-day evaluation.

PMID- 14682580
TI  - The microbial community analysis of a 5-stage BNR process with step feed system.
AB  - The microbial communities of 5-stage BNR activated sludge samples were analyzed
      using fluorescence in-situ hybridization (FISH) and 16S rDNA characterization.
      The total cell numbers of each reactor were from 2.36 x 10(9) cells/ml to 2.83 x
      10(9) cells/ml. From 56.5% to 62.0% of total DAPI cell counts were hybridized to
      the most bacterial specific probe EUB 338. Among them, beta-proteobacteria were
      most dominant in each tank. The number of phosphate accumulating organisms (PAOs)
      was almost 50% of the total cell number in anoxic-1 tank, and these results
      indicate that this process has a high content of denitrifying phosphorus
      accumulating organisms (dPAOs). In contrast with FISH, 16S rDNA analysis showed
      that dominant groups were the Cytophaga-Flavobacterium group and high G+C% gram
      positive bacteria, which were determined as PAOs in anoxic-1 tank. The beta
      subclass Proteobacteria did not accumulate a large amount of polyphosphate. The
      overall results indicate that high G+C% gram-positive bacteria and the Cytophaga
      Flavobacterium group might play a key role as dPAOs in this process.

PMID- 14682581
TI  - Enrichment of nitrifying microbial communities from shrimp farms and commercial
      inocula.
AB  - Nitrifying bacteria were selected from shrimp farm water and sediment ("natural"
      seed) in Thailand and from commercial seed cultures. The microbial consortia from
      each source giving the best ammonia removal during batch culture pre-enrichments
      were used as inocula for two sequencing batch reactors (SBRs). Nitrifiers were
      cultivated in the SBRs with 100 mg NH4-N/l and artificial wastewater containing
      25 ppt salinity. The two SBRs were operated at a 7 d hydraulic retention time
      (HRT) for 77 d after which the HRT was reduced to 3.5 d. The amounts of ammonia
      removed from the influent by microorganisms sourced from the natural seed were
      85% and 92% for the 7 d HRT and the 3.5 d HRT, respectively. The ammonia removals
      of microbial consortia from the commercial seed were 71% and 83% for these HRTs
      respectively. The quantity of ammonia-oxidizing bacteria (AOB) and nitrite
      oxidizing bacteria (NOB) was determined in the SBRs using the most probable
      number (MPN) technique. Both AOB and NOB increased in number over the long-term
      operation of both SBRs. According to quantitative fluorescence in situ
      hybridisation (FISH) probing, AOB from the natural seed and commercial seed
      comprised 21 +/- 2% and 30 +/- 2%, respectively of all bacteria. NOB could not be
      detected with currently-reported FISH probes, suggesting that novel NOB were
      enriched from both sources. Taken collectively, the results from this study
      provide an indication that the nitrifiers from shrimp farm sources are more
      effective at ammonia removal than those from commercial seed cultures.

PMID- 14682582
TI  - Effects of ferric ion on bioleaching of heavy metals from contaminated sediment.
AB  - Bioleaching is one of the promising procedures for removal of heavy metals from
      contaminated sediments. The advantages of this biotechnology are that it is easy,
      efficient, less costly and friendly to the environment. However, the principal
      disadvantage of this process is its slow kinetics in metal solubilization, which
      may limit practical application of the bioleaching process. In order to enhance
      the rate and efficiency of metal solubilization, the ferric ion was used as a
      catalytic agent in the bioleaching process. It was found that the sediment pH
      apparently decreased in the bioleaching after addition of ferric ion. The metal
      solubilization increased quickly after the addition of ferric ion. The rate of
      metal solubilization was enhanced by the addition of ferric ion, especially for
      Cr and Pb. An increase in the amount of ferric ion added increased the final
      efficiency of metal solubilization. The highest final efficiency of metal
      solubilization was obtained in the bioleaching with 1 g/L of ferric ion. Besides,
      the growth of sulfur-oxidizing bacteria was not affected by addition of ferric
      ion in the bioleaching. It was concluded that the kinetics of metal
      solubilization were enhanced by addition of ferric ion in the bioleaching
      process.

PMID- 14682583
TI  - The enzymology of sludge solubilisation utilising sulphate reducing systems: the
      role of lipases.
AB  - The first stage in the degradation and recycling of particulate organic matter is
      the solubilisation and enhanced hydrolysis of complex polymeric organic carbon
      structures associated with the sulphidogenic environment. An investigation into
      the enzymology of these processes has shown that lipase enzyme activities were
      found predominantly associated with the organic particulate matter of the sewage
      sludge. Sonication of the sludge gave an increase in enzyme activity as the
      enzymes were released into the supernatant. pH and temperature optimisation
      studies showed optima at between 6.5 and 8 and 50-60 degrees C, respectively. All
      the lipase enzymes from the methanogenic bioreactors indicated extensive
      stability for at least an hour at their respective optimum temperatures and pH;
      sulphidogenic lipases reflected limited stability at these temperatures and pH
      during this time period. Though sulphate showed inhibitory properties towards
      lipases both sulphide and sulphite appeared to enhance the activity of the
      enzymes. It is argued that these sulphur species, liberated at different times
      during the sulphate reduction process, disrupt the integrity of the organic
      particulate floc by neutralising acidic components on the surface. The release of
      further entrapped enzymes from the organic particulate matter results in a
      subsequent enhancement of hydrolysis of polymeric material.

PMID- 14682584
TI  - Bioleaching of metals from sludges and acid production under increased metal
      concentrations.
AB  - To remove heavy metals from sludge and slurries the heavy metals must first be
      solubilised. In this study, metal bioleaching using sulphuric acid producing
      microorganisms is investigated. The inhibitory effects of four metals (zinc,
      chromium, nickel and copper) on acid production were firstly assessed for
      concentrations of each metal up to 1,000 mg/l. Low concentrations of zinc and
      chromium (50 mg/L) appear to stimulate the production of sulphuric acid but
      concentrations of those metals at 500 mg/L and above inhibited acid production
      (20 to 30% of the control rate at a concentration of 1,000 mg/L). The average
      sulphuric acid production of the metal free control was 0.78 g/L/day over a 10
      day period. At all concentrations of nickel and copper, sulphuric acid production
      was suppressed and was less than 10% of the control at 250 mg/L or more after 10
      days. Activated sludge was also loaded with the four metals in individual
      bioleaching tests, in increments from zero up to 5,050 mg of metal/kg solids on a
      dry basis. In these bioleaching trials the sulphuric acid production averaged
      0.9/g/L/day and the pH after 7 days was less than 2.0. Sludge copper
      concentrations of 3,850 and 5,050 mg/kg partially inhibited acid production (pH
      after 7 days was 2.4 and 2.7). The solubilisation for each metal after 7 days was
      Zn: 82-97%, Ni: 12-70%, Cu: 28-55%, and Cr: <20%. Bioleaching of a sludge loaded
      with a mixture of the four metals gave peak solubilities of 99% for Zn after 3
      days, 68% for Ni after 6 days, 57% for Cu after 9 days and 33% for Cr after 9
      days.

PMID- 14682585
TI  - Biodegradation of polycyclic aromatic hydrocarbons (PAHs) by microbial consortia
      enriched from mangrove sediments.
AB  - Surface sediments from two mangrove swamps in Hong Kong were enriched to obtain
      PAH-degrading microbial consortia. The consortium from sediments enriched with
      phenanthrene (Phe) in Ma Wan, a mangrove swamp next to a boat anchorage, was
      effective in degrading PAH with 96.7% and 89.9% Phe degradation at 0 and 10 ppt
      salinities, respectively. The Phe-enriched microbial consortium could also use
      pyrene (Pyr) as the sole carbon source but the degradation was much less (around
      15%). On the other hand, the Phe-enriched consortium from sediments in Yi O, a
      mangrove swamp recently polluted by an oil spill, completely removed Phe and Pyr
      at both 0 and 10 ppt salinities. This suggests that different consortia were
      selected in two sediments using the same PAH substrate. Not only sediments, PAH
      substrate used for enrichment also selected different consortia. The Pyr- and Fla
      enriched Yi O consortia only achieved 10.5 and 4.5% Phe degradation, respectively
      and the corresponding pyrene degradation was 7 and 40%. Among the three PAH
      compounds, fluoranthene (Fla) was most difficult to degrade, and 21.1, 11.3, and
      36.8% Fla were degraded by Phe-, Fla- and Pyr-enriched cultures, respectively.

PMID- 14682586
TI  - Estimation of stoichiometric and kinetic coefficients of ASM3 under aerobic and
      anoxic conditions via respirometry.
AB  - Activated Sludge Model No. 1 (ASM 1) has been used extensively for the design and
      simulation of biological treatment systems. Batch respirometric experiments have
      been described in the model for the determination of model coefficients and
      respirometric studies have been proved to be useful in kinetic parameter
      estimation and wastewater characterisation for ASM 1. Activated Sludge Model No.
      3 (ASM3) has also introduced a number of kinetic and stoichiometric coefficients
      with the new processes defined in the model, also suggesting some default values.
      Recent studies on the application of ASM3 are limited to special cases in terms
      of parameter determination. Proper calibration of ASM3 parameters can be a
      difficult task without involving respirometric procedures as experimental tools.
      Respirometric batch tests were conveniently used in this study in order to
      estimate ASM3 parameters and the main kinetic and stoichiometric model
      coefficients were successfully and uniquely determined for aerobic and anoxic
      conditions for acetate.

PMID- 14682587
TI  - Application of a membrane bioreactor system for opto-electronic industrial
      wastewater treatment--a pilot study.
AB  - The membrane bioreactor (MBR) system has become more and more attractive in the
      field of wastewater treatment. It is particularly attractive in situations where
      long solids retention times are required, such as nitrifying bacteria, and
      physical retention is critical to achieving more efficiency for biological
      degradation of pollutants. Although it is a new technology, the MBR process has
      been applied to industrial wastewater treatment for only the past decade. The
      opto-electronic industry, developed very fast over the past decade in the world,
      is a high technological manufacturing industry. The treatment of the opto
      electronic industrial wastewater containing a significant quantity of organic
      nitrogen compounds, with a ratio over 95% in organic nitrogen (Org-N) to total
      nitrogen (T-N), is very difficult to meet the discharge limits. The purpose of
      this research is mainly to discuss the treatment capacity of high-strength
      organic nitrogen wastewater, and to investigate the capabilities of the MBR
      process. A 2 m3/day capacity MBR pilot plant consisting of anoxic and aerobic
      tanks and a membrane bioreactor was installed for evaluation. The operation was
      continued for 130 days. Over the whole experimental period, a satisfactory
      organic removal performance was achieved. The COD could be removed with an
      average of over 94.5%. For TOC and BOD5, the average removal efficiencies were
      96.3 and 97.6%, respectively. The nitrification and denitrification were also
      successfully achieved. The effluent did not contain any suspended solids. Only a
      small concentration of ammonia nitrogen was found in the effluent. The stable
      effluent quality and satisfactory removal performance mentioned above were
      ensured by the efficient interception performance of the membrane device
      incorporated within the biological reactor. The MBR system shows promise as a
      means of treating very high organic nitrogen wastewater without dilution. The
      effluent of TKN, NOx-N and COD can fall below 20 mg/L, 30 mg/L and 50 mg/L.

PMID- 14682588
TI  - A new method for the fast determination of kinetic parameters in anaerobic
      digestion processes and application to textile wet processing wastewater.
AB  - A new method for the fast and efficient determination of the anaerobic
      degradability and for the calculation of kinetic parameters is proposed. It is
      based on the idea that monitoring of the acidification step in the anaerobic
      degradation cascade is sufficient, as the subsequent steps (acetogenesis,
      methanogenesis) are well known processes dependent on the intermediate
      concentrations and not on the original substrate used. The investigation of the
      acidification is subdivided into two steps. In the first step, biomass is adapted
      to the new substrate in a continuously operated bioreactor. The second step, the
      only step monitored, is the acidification of the substrate (or wastewater) in a
      batch experiment. Three different methods to monitor the acidification were
      tested: gas chromatography (offline), on-line titration and monitoring of the
      base consumption (direct titration). The results of these methods were compared
      to "traditional" batch tests. It is shown that the simplest method (direct
      titration) revealed the most important information. The investigated substrates
      were selected pollutants of textile wet processing wastewater.

PMID- 14682589
TI  - Solubilization of waste activated sludge by alkaline pretreatment and biochemical
      methane potential (BMP) tests for anaerobic co-digestion of municipal organic
      waste.
AB  - Biochemical methane potential (BMP) tests have been carried out to determine the
      anaerobic digestibility of the waste activated sludge (WAS) and the sludge
      pretreated by NaOH (PWAS). The optimal NaOH dosage was determined to be 45 meq
      NaOH/L. The maximum SCOD solubilization was 27.7, 31.4 and 38.3% at the
      temperatures of 25, 35 and 55 degrees C respectively after 4 hours reaction. The
      final methane yield of simulated food waste (SFW) was 430 ml CH4/g VS(added), and
      those of PWAS (25 degrees C), PWAS (35 degrees C) and PWAS (55 degrees C) was
      274, 286 and 310 ml CH4/g VS(added) respectively after 20 days. The figures were
      66%, 73% and 88% higher than that of WAS. The methane production in anaerobic co
      digestion is considerably affected by the fraction of SFW and PWAS in the feed.
      The anaerobic digestibility of the feed mixture (SFW with PWAS) is higher than
      that of the feed mixture (SFW with WAS). Anaerobic co-digestion of food waste
      with the PWAS is found to be an attractive option to reduce the solid waste
      volume with improved methane recovery.

PMID- 14682590
TI  - Polyhydroxyalkanoate (PHA) production from waste.
AB  - PHA (polyhydroxyalkanoate) production was attempted with SBRs from food waste.
      Seed microbes were collected from a sewage treatment plant with a biological
      nutrient removal process, and acclimated with synthetic substrate prior to the
      application of the fermented food waste. Laboratory SBRs were used to produce PHA
      with limited oxygen and nutrients. The maximum content of 51% PHA was obtained
      with an anaerobic/aerobic cycle with P limitation, and the yield was estimated to
      be about 0.05 gPHA(produced)/gCOD(applied) or 25 kg PHA/dry ton of food waste,
      assuming more than 40% of the PHA contents were recoverable. PHB/PHA ratios were
      0.74 to 0.77 due to the higher acetate concentrations. Economical analysis seemed
      to suggest the PHA produced from the food waste could be an alternative material
      to produce the biodegradable plastic to be used for the collection bags for solid
      waste.

PMID- 14682591
TI  - Improved process control with a pHauxostat for application in biotechnology.
AB  - The pHauxostat is a unique control technique which was proposed nearly half a
      century ago but has found limited use up to date. This study highlights the
      results whereby the pHauxostat was analysed, categorized and a theory developed.
      pHauxostats can be categorised into Category A or B pHauxostats and further sub
      divided into A1 or A2 and B1 or B2. The pHauxostat is successfully modelled by
      using alkalinity as a parameter whereby an alkalinity yield coefficient is
      defined. This alkalinity yield coefficient can be determined by applying half
      reactions, and together with traditional biological growth models the process can
      be described theoretically. This enables the applications of the technique in a
      predictable and controlled way with the possibility of wider use. The technique
      can be described as a self-regulating control technique in biotechnology whereby
      the pH is used as the controlled output variable and the feed (rate and/or
      concentration) the manipulated input variable.

PMID- 14682592
TI  - Production of biopesticides using wastewater sludge as a raw material--effect of
      process parameters.
AB  - Production of Bacillus thuringiensis (Bt) based biopesticide was studied using
      hydrolysed or raw wastewater sludge as a raw material. The sludge hydrolysis was
      carried out at different pH (2, 4 and 6). The sludge after hydrolysis was
      sterilised at 121 degrees C for 30 minutes. The effect of temperature, pH and
      agitation speed on growth and toxin production was also investigated. The pH in
      the shake flask was controlled by adding 0.1 M TRIS buffer. The progress of the
      biopesticide production process was monitored by measuring viable cell count
      (VC), spore count (SC) and entomotoxicity (Tx). The entomotoxicity was measured
      against spruce budworm. Control of pH substantially increased the entomotoxicity
      of the final product. Increased agitation speed resulted in higher VC, SC and Tx
      values.

PMID- 14682593
TI  - Effect of oxygen on the stability and inducibility of the biodegradative
      capability of benzoate.
AB  - Anoxic zones in biological nitrogen removal systems are typically open to the
      atmosphere and receive oxygen from the atmosphere and the recirculation flow from
      the aerobic zone. This raises the question of how such oxygen input might
      influence the stability and inducibility of the enzyme systems involved in
      biodegradation of aromatic compounds. To investigate this, various amounts of
      oxygen were added to mixed culture denitrifying chemostats receiving benzoate at
      667 mg/h as chemical oxygen demand (COD), and the stability and inducibility of
      the culture's benzoate biodegradative capability (BBC) were tested in aerobic and
      anoxic fed-batch reactors (FBRs). Cultures from chemostats receiving oxygen at 0,
      33, 133, 266, and 466 mg O2/h lost almost all of their anoxic BBC within one hour
      after being transferred to an aerobic FBR and the first three cultures did not
      recover it upon being returned to anoxic conditions. The last two cultures
      recovered their anoxic BBC between 9 and 16 h during the 16 h aerobic exposure
      period that preceded their return to anoxic conditions and continued to increase
      their anoxic BBC as they were retained under anoxic conditions. In contrast, the
      culture from a chemostat receiving oxygen at 67 mg O2/h retained its anoxic BBC
      longer, recovered it within 3 h after its return to anoxic conditions, and
      increased it linearly thereafter. None of the cultures developed any aerobic BBC
      during the 16 h aerobic exposure period in FBRs. The results suggest that higher
      oxygen inputs into anoxic reactors helped the mixed microbial cultures recover
      and/or induced anoxic BBC more easily when they were exposed to alternating
      aerobic/anoxic environments. The exceptional behavior of the culture from the
      chemostat receiving oxygen at a rate of 67 mg O2/h may have been caused by the
      presence of a protective mechanism against the toxic forms of oxygen.

PMID- 14682594
TI  - Elucidation mechanism of organic acids production from organic matter (grass)
      using digested and partially digested cattle feed.
AB  - The process of anaerobic digestion is highly influenced by the environmental and
      operational factors like organic acids concentration and the reactor volume
      occupied by the feed material. The optimum level of organic acids is commonly
      assumed to be in the range between 2,500 and 3,500 mg/l for the anaerobic
      digestion process. It was observed that the production of total organic acids
      during hydrolysis of grass using cattle dung slurry (CDS) as the inoculum reached
      up to 4,850 mg/l in 6 days, while on the other hand it reached 5,700 mg/l within
      4 days when rumen content was used as inoculum. The organic acids production
      continued to the 30th day in the case of rumen content, while in the case of CDS
      it stopped within 10 days because of pH drop. As compared to CDS the anaerobic
      digestion of grass with rumen content showed better degradation and biogas
      production with nearly 80% of methane and up to 80 and 95% reduction in chemical
      oxygen demand and organic acids respectively.

PMID- 14682595
TI  - Substrata effects on bacterial biofilm development in a subsurface flow dairy
      waste treatment wetland.
AB  - Biofilm development on two distinct rock substrata was investigated both in vitro
      and in a subsurface flow wastewater treatment wetland in order to determine the
      effect of hydrophobicity on initial bacterial adsorption, tertiary biofilm
      development and microbial population structure. Two commonly used wetland rock
      types, slag (a hydrophobic by-product of the steel smelter industry) and
      greywacke (a more hydrophilic sedimentary rock) were evaluated. In vitro
      investigations of initial microbial adsorption trends showed that the more
      hydrophobic slag displayed rapid bacterial adsorption rates compared to
      greywacke. Mean microbial adsorption rates of a mixed wetland bacterial
      population over 5 hours, described using a first order kinetics model, were 1.3 x
      10(-12) m/sec for slag and consistently lower at 8.7 x 10(-13) m/sec for
      greywacke. Pristine rock studs of the two substrata were also exposed to wetland
      microbial communities during a six week field trial using confocal scanning laser
      microscopy to determine tertiary biofilm structure and fluorescent in situ
      hybridisation to investigate bacterial populations. During the first five weeks
      of growth CSLM analysis revealed that 75% of biofilms on slag were thicker and
      had greater coverage compared with those grown on greywacke. After six weeks of
      growth over 50% of the tertiary biofilms were structurally very similar on both
      rock types and only 25% of those grown on slag were larger than those on
      greywacke. In situ hybridisation analysis of bacterial populations revealed very
      little difference in population structure between biofilms grown on slag and
      those grown on greywacke. Eubacteria were present as a very high proportion of
      total bacteria throughout biofilm development (74.3%). The beta subgroup was the
      most populous of the Proteobacteria (31.4%) followed by the gamma subgroup
      (13.4%) and the alpha subgroup (1.3%). The results of this study suggest that
      slag, as a more hydrophobic substratum, promotes the initial adsorption of
      bacteria during early biofilm growth and better supports mature biofilm
      structures when used in wetlands. This study has implications for the design and
      construction of wastewater treatment wetlands.

PMID- 14682596
TI  - Historical perspectives.
AB  - The history of surgery for emphysema is filled with numerous surgical attempts to
      improve the disorder. Although many of these procedures have proved to be futile,
      lung volume reduction surgery has now arrived. This article outlines the
      progression of procedures and the logic for which they were thought to be of
      benefit.

PMID- 14682597
TI  - Pathophysiology and classification of emphysema.
AB  - Current research is providing new understanding in the pathophysiology of
      emphysema, and this knowledge will be translated in finding better modalities of
      therapy for patients currently affected by COPD. The single best effort that can
      alter the course of COPD is promoting policies to remove smoking as an available
      option to young people, before they become addicted and thus prey of tobacco
      producing companies. Landmark studies like NETT and the GOLD initiative are
      providing tool classify emphysema in the context of physiological criteria and
      possible therapeutic alternatives.

PMID- 14682598
TI  - Medical management of chronic obstructive pulmonary disease.
AB  - Recent advances in the treatment of patients who have COPD include the
      development of long-acting bronchodilators, recognition of the benefits of ICS,
      and development of effective initiation and maintenance pulmonary rehabilitation
      programs. The focus on outcome parameters other than expiratory flow rates, such
      as symptoms, quality of life, exercise tolerance, and exacerbation frequency,
      might also allow effective development of novel disease-modifying agents.

PMID- 14682599
TI  - Giant bullous lung disease: evaluation, selection, techniques, and outcomes.
AB  - Patient selection remains one of the most important aspects of successful surgery
      for bullous disease. Operation is indicated for patients who have incapacitating
      dyspnea with large bullae that fill more than 30% of the hemithorax and result in
      the compression of healthy adjacent lung tissue. Operation is also indicated for
      patients who have complications related to bullous disease such as infection or
      pneumothorax. Patients who have bullous disease in the presence of diffuse lung
      disease (emphysematous or nonemphysematous) should be evaluated on an individual
      basis and surgery should be performed on patients in whom even a small increase
      in pulmonary function might be of major benefit. Smoking cessation and outpatient
      pulmonary rehabilitation are required of all patients preoperatively. Patients
      should undergo PFTs including lung volumes by whole body plethysmography,
      spirometry, diffusion capacity, and arterial blood gas. CT remains the most
      important preoperative evaluation because it is useful assessing the extent of
      bullous disease and the quality of the surrounding lung tissue. The authors favor
      a minimally invasive technique through VATS whenever possible because it might
      allow for a quicker recovery and might be associated with less pain than is seen
      following thoracotomy. Modified Monaldi-type drainage procedures are also
      effective, especially in high-risk patients who cannot tolerate excisional
      procedures. Special care must be taken to avoid sacrifice of any potentially
      functional lung tissue. Lobectomies should be avoided whenever possible. The best
      results are seen in limited resections of large bullae that spare all surrounding
      functional pulmonary parenchyma. Postoperative complications are minimized
      through aggressive tracheobronchial toilet and vigorous chest physiotherapy.
      Adequate pain control in maintained throughout the postoperative period,
      initially by way of epidural infusion of morphine or fentanyl and later through
      oral opioids. Early ambulation and pulmonary rehabilitation also help minimize
      complications.

PMID- 14682600
TI  - Lung transplantation for emphysema.
AB  - Great strides have been made in lung transplantation in the past two decades.
      Changes in technique, immunosuppression regimens, and treatment of infectious
      complications have led to improvements in survival and functional results.
      Current areas of discussion concern the use of single lung transplantation versus
      bilateral sequential lung transplantation and the criteria for allocating donor
      lungs. This article reviews the current state of lung transplantation for
      emphysema and provides insight from more than one decade of experience with
      Washington University's lung transplant program.

PMID- 14682601
TI  - Patient selection for lung volume reduction surgery.
AB  - LVRS represents a valid surgical option for a limited number of patients who have
      symptomatic emphysema. The results of recent controlled studies have provided a
      realistic view of LVRS outcomes and yielded a validated algorithm for selection
      of optimal candidates for surgery. Furthermore, the NETT has provided
      simultaneously collected cost data that have provided a unique view of the costs
      and benefits of LVRS in patients who have advanced emphysema. Additional data
      collection will better define the long-term benefits of such surgical
      intervention in patients who have COPD.

PMID- 14682602
TI  - Operative techniques for lung volume reduction surgery.
AB  - Recently, LVRS has received renewed public interest. Various surgical approaches
      and techniques exist, and each has challenges, advantages, and disadvantages.
      Stapled techniques have been used more commonly than plication techniques or
      lasers. The choice of staple buttressing material has not been shown to affect
      outcome. For most patients who are suitable for LVRS, a bilateral procedure is
      appropriate. Minimally invasive techniques are gaining in popularity and have
      demonstrated good results. Of the approaches discussed above, bilateral
      thoracoscopy in the supine position is likely to be the most expeditious with the
      lowest incision-related morbidity and dysfunction.

PMID- 14682603
TI  - Complications after lung volume reduction surgery.
AB  - LVRS has greater morbidity than most general thoracic surgical procedures. Proper
      care of patients after LVRS is a labor-intensive activity, but it is worthwhile
      because LVRS can be performed with acceptable risk. Patient selection,
      postoperative care, and an understanding of the potential complications are the
      keys to successful LVRS.

PMID- 14682604
TI  - Results of lung volume reduction surgery for emphysema.
AB  - LVRS provides an exciting opportunity for palliation of symptoms and improvement
      in quality of life for patients who have severe end-stage emphysema. Because no
      medical therapy has been able to improve pulmonary function or reverse the
      inexorable decline of breathless patients who have emphysema, this opportunity to
      improve lung function and quality of life is one of the most innovative additions
      to thoracic surgery since the first successful lung transplant procedure 20 years
      ago. Although initial short-term, case-controlled surgeries were criticized
      because of incomplete and short follow-up care, substantial long-term data now
      exist to support the use of LVRS for select patients who have severe emphysema.
      Patients who have upper lobe predominant disease or low exercise capacity are
      more likely to have a benefit in exercise capacity and quality of life after
      LVRS. Selected patients who have upper lobe emphysema and poor exercise capacity
      are also more likely to have improved survival after LVRS. The individual
      contributions by the large number of investigators pioneering LVRS development,
      along with the collective contributions of the NETT investigators, have propelled
      the knowledge surrounding LVRS far beyond that of any similar new technology or
      procedure in its adolescence.

PMID- 14682605
TI  - Cost effectiveness of lung volume reduction surgery.
AB  - Lung volume reduction surgery (LVRS) is a costly new procedure that could
      influence quality of life and survival for persons who have severe emphysema.
      This article reviews the history of LVRS from an economic and policy perspective
      and provides estimates of the cost effectiveness of LVRS derived from the
      National Emphysema Treatment Trial, a recently completed multicenter evaluation
      of LVRS, compared with medical care. Estimates of the potential impact of LVRS on
      the national health care budget are provided. The high cost and uncertainty
      regarding the long-term cost effectiveness of LVRS warrant further evaluation
      after public and private health insurers make coverage decisions for this
      procedure, particularly if it is adopted as part of the standard of care.

PMID- 14682606
TI  - New treatment modalities for end-stage emphysema.
AB  - The concept of nonresectional LVRS appears to be highly promising. Several
      strategies and approaches are currently available; however, the investigations to
      date are still just studies, and there remain many unanswered questions. No doubt
      new modifications and improvements in design will occur and these devices will
      continue to evolve. Appropriate patient selection is, as always, the key to good
      outcome. The studies so far have included only patients who have heterogenous
      disease; whether or not the procedures can be helpful for patients who have
      homogenous distribution of emphysema remains to be seen. Radioactive isotope
      scans are currently being used in an attempt to identify patients who have
      significant collateral flow, and these scans might eventually be useful in
      selecting patients who are unlikely to benefit from this approach. The
      preliminary data remain encouraging and suggest that a larger study with long
      term follow-up care is warranted.

PMID- 14682607
TI  - Reversal of statin toxicity to human lymphocytes in tissue culture.
AB  - Hydroxymethylglutaryl-CoA reductase inhibitors (statins) are widely used to
      inhibit biosynthesis of cholesterol in individuals with elevated serum levels of
      this risk factor for cardiovascular disease. We find that statins are toxic to
      human lymphocytes in cell culture at concentrations less than 0.1 microg/ml.
      Addition of their own plasma reverses this toxicity in some, but not all,
      individuals. Addition of coenzyme Q10 (CoQ10) with plasma is more effective than
      plasma alone in reversing toxicity in some individuals. Apparently, two factors
      are required to reverse the cellular toxicity of statins: CoQ10 and a plasma
      factor found in a subset of individuals. These observations may provide the basis
      for a method to assess individual susceptibility to statin toxicity and to
      predict which individuals may benefit from supplements of CoQ10.

PMID- 14682608
TI  - Interaction between fibrates and statins--metabolic interactions with
      gemfibrozil.
AB  - An in vitro study was carried out in order to examine the metabolic basis of the
      interaction between fibrates and statins. Metabolic inhibition of statins was
      noted in the presence of gemfibrozil. However, increase in the unchanged form was
      fairly small for pitavastatin, compared with other statins. Several CYP enzymes
      were shown to be principally responsible for the metabolism of gemfibrozil in
      contrast to other fibrates. In the presence of gemfibrozil, a focal point was
      obtained in Dixon plots, demonstrating that there was inhibition of CYP2C8-,
      CYP2C9- and CYP3A4-mediated metabolism. We propose that the increase of plasma
      concentration caused by co-administration of gemfibrozil and statins is at least
      partially due to CYP-mediated inhibition.

PMID- 14682609
TI  - Possible interaction of herbal tea and carbamazepine.
AB  - A study was conducted using Wistar rats to determine the effect of concurrent
      administration of a herbal tea prepared from dried flowers of Cassia auriculata
      and carbamazepine on (a) blood levels of the prescription drug and (b) changes in
      toxicity (as assessed by changes in hematological parameters, liver and kidney
      function, and histology of major body organs) that may occur due to drug
      interaction. Results demonstrate that in rats receiving the herbal tea and
      carbamazepine, the blood levels of the prescription drug were significantly
      enhanced by 47.1% (p <0.04) when compared with the levels in animals receiving
      only carbamazepine, with no apparent changes in toxicity. Concurrent ingestion of
      the herbal tea prepared from Cassia auriculata flowers with carbamazepine may
      therefore influence the bioavailability of the prescribed drug and hence its
      therapeutic potential.

PMID- 14682610
TI  - A molecular model of CYP2D6 constructed by homology with the CYP2C5
      crystallographic template: investigation of enzyme-substrate interactions.
AB  - The results of homology modelling of CYP2D6 based on the mammalian P450 crystal
      structure of rabbit CYP2C5 are reported. It is found that many CYP2D6-selective
      substrates are able to fit closely within the putative active site of the enzyme
      where there are favourable contacts with complementary amino acid residues,
      including aspartate-301 which has been probed via site-directed mutagenesis. The
      homology model of CYP2D6 is consistent with available experimental evidence from
      selective substrate metabolism and site-specific mutation data. Quantitative
      structure-activity relationships (QSARs) with substrate binding affinity based on
      KD values and inhibition data (Ki values) demonstrate the importance of hydrogen
      bonding, pi-pi stacking and relative molecular mass in describing variations in
      avidity towards the CYP2D6 enzyme, although the compound lipophilicity (log
      D(7.4)) appears to be the most important single descriptor for CYP2D6 inhibition.
      Calculation of substrate binding affinity based on contributions from active site
      interactions and lipophilic character gives satisfactory agreement with
      experimentally determined KD values.

PMID- 14682611
TI  - Withania somnifera (Ashwagandha) attenuates antioxidant defense in aged spinal
      cord and inhibits copper induced lipid peroxidation and protein oxidative
      modifications.
AB  - Withania somnifera is classified in Ayurveda, the ancient Indian system of
      medicine, as a rasayana, a group of plant-derived drugs which promote physical
      and mental health, augment resistance of the body against disease and diverse
      adverse environmental factors, revitalize the body in debilitated conditions and
      increase longevity. We investigated the effects of Withania somnifera on copper
      induced lipid peroxidation and antioxidant enzymes in aging spinal cord of Wistar
      rats. The activity of glutathione peroxidase (GPx) decreased significantly in the
      spinal cord from adult to aged mice. Treatment with Withania somnifera
      successfully attenuated GPx activity and inhibited lipid peroxidation in a dose
      dependent manner. Withania somnifera inhibited both the lipid peroxidation and
      protein oxidative modification induced by copper. These effects were similar to
      those of superoxide dismutase and mannitol. The results indicate the therapeutic
      potential of Withania somnifera in aging and copper-induced pathophysiological
      conditions.

PMID- 14682612
TI  - Comparative analysis of expressed sequence tags from Sesamum indicum and
      Arabidopsis thaliana developing seeds.
AB  - Sesame (Sesamum indicum) is an important oilseed crop which produces seeds with
      50% oil that have a distinct flavor and contains antioxidant lignans. Because
      sesame lignans are known to have antioxidant and health-protecting properties,
      metabolic pathways for lignans have been of interest in developing sesame seeds.
      As an initial approach to identify genes involved in accumulation of storage
      products and in the biosynthesis of antioxidant lignans, 3328 expressed sequence
      tags (ESTs) were obtained from a cDNA library of immature seeds 5-25 days old.
      ESTs were clustered and analyzed by the BLASTX or FASTAX program against the
      GenBank NR and Arabidopsis proteome databases. To compare gene expression
      profiles during development of green and non-green seeds, a comparative analysis
      was carried out between developing sesame and Arabidopsis seed ESTs. Analyses of
      these two seed EST sets have helped to identify similar and different gene
      expression profiles during seed development, and to identify a large number of
      sesame seed-specific genes. In particular, we have identified EST candidates for
      genes possibly involved in biosynthesis of sesame lignans, sesamin and sesamolin,
      and also suggest a possible metabolic pathway for the generation of cofactors
      required for synthesis of storage lipid in non-green oilseeds. Seed-specific
      expression of several candidate genes has been confirmed by northern blot
      analysis.

PMID- 14682613
TI  - CHB2, a member of the SWI3 gene family, is a global regulator in Arabidopsis.
AB  - The SWI/SNF complex is an ATP-dependent chromatin remodeling complex that plays
      an important role in the regulation of eukaryotic gene expression. Very little is
      known about the function of SWI/SNF complex in plants compared with animals and
      yeast. SWI3 is one of the core components of the SWI/SNF chromatin remodeling
      complexes in yeast. We have identified a putative SWI3-like cDNA clone, CHB2
      (AtSWI3B), from Arabidopsis thaliana by screening the expressed sequence tag
      database. CHB2 encodes a putative protein of 469 amino acids and shares 23% amino
      acid sequence identity and 64% similarity with the yeast SWI3. The Arabidopsis
      genome contains four SWI3-like genes, namely CHB1 (AtSWI3A), CHB2 (AtSWI3B), CHB3
      (AtSWI3C) and CHB4 (AtSWI3D). The expression of CHB2, CHB3 and CHB4 mRNA was
      detected in all tissues analyzed by RT-PCR. The expression of CHB1 mRNA, however,
      could not be detected in the siliques, suggesting that there is differential
      expression among CHB genes in different Arabidopsis tissues. To investigate the
      role of CHB2 in plants, Arabidopsis plants were transformed with a gene construct
      comprising a CHB2 cDNA in the antisense orientation driven by the CaMV 35S
      promoter. Repression of CHB2 expression resulted in pleiotropic developmental
      abnormalities including abnormal seedling and leaf phenotypes, dwarfism, delayed
      flowering and no apical dominance, suggesting a global role for CHB2 in the
      regulation of gene expression. Our results indicate that CHB2 plays an essential
      role in plant growth and development.

PMID- 14682614
TI  - Multiple conserved 5' elements are required for high-level pollen expression of
      the Arabidopsis reproductive actin ACT1.
AB  - The Arabidopsis thaliana actin gene family comprises eight genes, which are
      divided into two ancient classes, vegetative and reproductive. We dissected
      various 5' elements and the conserved expression pattern of the reproductive
      actin gene ACT1, which is the most strongly expressed pollen actin gene. A basal
      construct containing only 310 bp of sequence upstream of the major
      transcriptional start site showed essentially full promoter activity in pollen
      and ovules. Further truncations of the 5'-flanking region and two different 10 bp
      replacements within a 55 bp conserved domain each caused a several-fold reduction
      in mature pollen expression. Intron L, located in the 5'-untranslated region (5'
      UTR) was also required for high-level expression of pollen and organ primordia,
      and it had the properties of an enhancer. Pollen expression was not preserved
      when intron L was precisely replaced by intron L2 from the vegetatively expressed
      actin gene ACT2. ACT1 reporter gene constructs were strongly expressed in both
      pollen and ovules of tobacco and in the pollen of rice. Promoter-reporter fusions
      of the most distantly related Arabidopsis reproductive actin gene ACT1 showed
      strong expression in tobacco pollen and ovules indistinguishable from that
      directed by ACT1. Thus, multiple conserved cis-sequence elements within the 5'
      flanking region and 5'-UTR of ACT1 direct high levels of reproductive tissue
      specific expression.

PMID- 14682617
TI  - Characterization of an Arabidopsis mutant deficient in gamma-tocopherol
      methyltransferase.
AB  - Alpha-tocopherol (vitamin E) is synthesized from gamma-tocopherol in chloroplasts
      by gamma-tocopherol methyltransferase (gamma-TMT; VTE4). Leaves of many plant
      species including Arabidopsis contain high levels of alpha-tocopherol, but are
      low in gamma-tocopherol. To unravel the function of different forms of tocopherol
      in plants, an Arabidopsis plant (vte4-1) carrying a functional null mutation in
      the gene gamma-TMT was isolated by screening a mutant population via thin-layer
      chromatography. A second mutant allele (vte4-2) carrying a T-DNA insertion in the
      coding sequence of gamma-TMT was identified in a T-DNA tagged mutant population.
      In vte4-1 and vte4-2 leaves, high levels of gamma-tocopherol accumulated, whereas
      alpha-tocopherol was absent indicating that, presumably, these two mutants
      represents null alleles. Over-expression of the gamma-TMT cDNA in vte4-1 restored
      wild-type tocopherol composition. Mutant plants were very similar to wild type.
      During oxidative stress (high light, high temperature, cold treatment) the
      amounts of alpha-tocopherol and gamma-tocopherol increased in wild type, and
      gamma-tocopherol in vte4-1. However, chlorophyll content and photosynthetic
      quantum yield were very similar in wild type and vte4-1, suggesting that alpha
      tocopherol can be replaced by gamma-tocopherol in vte4-1 to protect the
      photosynthetic apparatus against oxidative stress. Fatty acid and lipid
      composition were very similar in WT, vte4-1 and vte1, an Arabidopsis mutant
      previously isolated which is completely devoid of tocopherol. Therefore, a shift
      in tocopherol composition or the absence of tocopherol has no major impact on the
      amounts of specific fatty acids or on lipid hydrolysis.

PMID- 14682615
TI  - Repression of formate dehydrogenase in Solanum tuberosum increases steady-state
      levels of formate and accelerates the accumulation of proline in response to
      osmotic stress.
AB  - Formate dehydrogenase (FDH, EC 1.2.1.2.) is a soluble mitochondrial enzyme
      capable of oxidizing formate into CO2 in the presence of NAD+. It is abundant in
      non-green tissues and scarce in photosynthetic tissues. Under stress, FDH
      transcripts (and protein) accumulate in leaves, and leaf mitochondria acquire the
      ability to use formate as a respiratory substrate. In this paper, we describe the
      analysis of transgenic potato plants under-expressing FDH, obtained in order to
      understand the physiological function of FDH. Plants expressing low FDH
      activities were selected and the study was focused on a line (AS23) showing no
      detectable FDH activity. AS23 plants were morphologically indistinguishable from
      control plants, and grew normally under standard conditions. However,
      mitochondria isolated from AS23 tubers could not use formate as a respiratory
      substrate. Steady-state levels of formate were higher in AS23 leaves and tubers
      than in control plants. Tubers of untransformed plants oxidized 14C formate into
      14CO2 but AS23 tubers accumulated it. In order to reveal a possible phenotype
      under stress conditions, control and AS23 plants were submitted to drought and
      cold. These treatments dramatically induced FDH transcripts in control plants
      but, whatever the growth conditions, no 1.4 kb FDH transcripts were detected in
      leaves of AS23 plants. Amongst various biochemical and molecular differences
      between stressed AS23 and control plants, the most striking was a dramatically
      faster accumulation of proline in the leaves of drought-stressed plants under
      expressing FDH.

PMID- 14682616
TI  - Auxin distribution in Lotus japonicus during root nodule development.
AB  - For this work, Lotus japonicus transgenic plants were constructed expressing a
      fusion reporter gene consisting of the genes beta-glucuronidase (gus) and green
      fluorescent protein (gfp) under control of the soybean auxin-responsive promoter
      GH3. These plants expressed GUS and GFP in the vascular bundle of shoots, roots
      and leafs. Root sections showed that in mature parts of the roots GUS is mainly
      expressed in phloem and vascular parenchyma of the vascular cylinder. By
      detecting GUS activity, we describe the auxin distribution pattern in the root of
      the determinate nodulating legume L. japonicus during the development of
      nodulation and also after inoculation with purified Nod factors, N
      naphthylphthalamic acid (NPA) and indoleacetic acid (IAA). Differently than white
      clover, which forms indeterminate nodules, L. japonicus presented a strong GUS
      activity at the dividing outer cortical cells during the first nodule cell
      divisions. This suggests different auxin distribution pattern between the
      determinate and indeterminate nodulating legumes that may be responsible of the
      differences in nodule development between these groups. By measuring of the GFP
      fluorescence expressed 21 days after treatment with Nod factors or bacteria we
      were able to quantify the differences in GH3 expression levels in single living
      roots. In order to correlate these data with auxin transport capacity we measured
      the auxin transport levels by a previously described radioactive method. At 48 h
      after inoculation with Nod factors, auxin transport showed to be increased in the
      middle root segment. The results obtained indicate that L. japonicus transformed
      lines expressing the GFP and GUS reporters under the control of the GH3 promoter
      are suitable for the study of auxin distribution in this legume.

PMID- 14682618
TI  - Isolation and characterization of a novel rice Ca2+-regulated protein kinase gene
      involved in responses to diverse signals including cold, light, cytokinins,
      sugars and salts.
AB  - We have isolated a cold-inducible gene (designated OsCK1) from Oryza sativa by a
      differential cDNA screening technique. Sequence analysis indicated that the open
      reading frame of the OsCK1 gene consists of 1350 bp encoding 449 amino acid
      residues, which is very similar to a family of calcineurin B-like protein (CBL)
      interacting protein kinases (CIPKs) or salt overly sensitive 2 (SOS2)-like
      protein kinases (PKS) in Arabidopsis. CIPKs/PKS are a group of Ser/Thr protein
      kinases associated with the AtCBL/SOS3-like calcium-binding proteins (SCaBP).
      OsCK1 actually interacts with AtCBL3 through the C-terminal region in a yeast two
      hybrid system, suggesting that OsCK1 is probably a rice orthologue of one of the
      CIPK/PKS members. Expression of the OsCK1 gene was detected mainly in the shoots
      and highly inducible by diverse signals such as cold, light, salt, sugar and
      cytokinins. In addition, calcium increased the OsCK1 transcript level, whereas a
      calcium ionophore, A23187, partially abolished stimulus-induced expressions.
      OsCK1 phosphorylated itself and a generic substrate, myelin basic protein, in the
      preference of Mn2+. Deletion of the C-terminal region from OsCK1 significantly
      decreased autophosphorylation activity without affecting the ability for
      substrate phosphorylation. These findings suggest that the CBL/CIPK or SCaBP/PKS
      signaling pathways recently found in Arabidopsis may also exist in rice and
      function in cold response in which calcium signal serves as a second messenger.

PMID- 14682619
TI  - Dual positional specificity and expression of non-traditional lipoxygenase
      induced by wounding and methyl jasmonate in maize seedlings.
AB  - Lipoxygenases (LOXs) catalyze the formation of fatty acid hydroperoxides involved
      in responses to stresses. This study examines the expression of a non-traditional
      dual positional specific maize LOX in response to wounding or methyl jasmonate
      (MeJA). Full-length maize LOX cDNA was expressed in Escherichia coli, and
      recombinant LOX was purified and characterized enzymatically. RP-HPLC and GC-MS
      analysis showed that the purified LOX converts alpha-linolenic acid into 13
      hydroperoxylinolenic acid and 9-hydroperoxylinolenic acid in a 6:4 ratio. LOX
      mRNA accumulated rapidly and transiently in response to wounding reaching a peak
      of expression about 3 h after wounding. This increase followed an initial
      increase in endogenous jasmonic acid (JA) 1 h after wounding (JA burst). However,
      the expression of LOX induced by MeJA lasted longer than the expression induced
      by wounding, and the MeJA-induced expression seemed to be biphasic pattern
      composed of early and late phases. The expression of LOX in the presence of
      inhibitors of JA biosynthesis was not completely inhibited, but delayed in wound
      response and the expression period was shortened in MeJA response. These results
      suggest that wound-responsive JA burst may trigger the early phase of LOX
      expression which facilitates biosynthesis of endogenous JA through its 13-LOX
      activity, and subsequently leads to the activation of the late phase LOX
      expression in MeJA-treated maize seedlings. Implications of dual positional
      specificity of maize LOX in the observed expression kinetics are discussed.

PMID- 14682620
TI  - The SELF-PRUNING gene family in tomato.
AB  - The SELF PRUNING (SP) gene controls the regularity of the vegetative-reproductive
      switch along the compound shoot of tomato and thus conditions the 'determinate'
      (sp/sp) and 'indeterminate' (SP_) growth habits of the plant. SP is a
      developmental regulator which is homologous to CENTRORADIALIS (CEN) from
      Antirrhinum and TERMINAL FLOWER 1 (TFL1) and FLOWERING LOCUS T (FT) from
      Arabidopsis. Here we report that SP is a member of a gene family in tomato
      composed of at least six genes, none of which is represented in the tomato EST
      collection. Sequence analysis of the SP gene family revealed that its members
      share homology along their entire coding regions both among themselves and with
      the six members of the Arabidopsis family. Furthermore, members of the gene
      family in the two species display a common genomic organization (intron-exon
      pattern). In tomato, phylogenetically close homologues diverged considerably with
      respect to their organ expression patterns while SP2I and its closest homologue
      from Arabidopsis (MFT) exhibited constitutive expression. This research focusing
      on a plant of sympodial growth habit sets the stage for a functional analysis of
      this weakly expressed gene family which plays a key role in determining plant
      architecture.

PMID- 14682622
TI  - Unidirectional SAW transducer for gigahertz frequencies.
AB  - A single-phase unidirectional transducer (SPUDT) structure using lambda/4 and
      wider electrodes is introduced. The considerable difference between the
      reflectivity of short-circuited lambda/4 electrodes and that of floating lambda/2
      wide electrodes on 128 degree lithium niobate (LiNbO3) is exploited. The surface
      acoustic wave (SAW) device operating at 2.45 GHz has critical dimensions of about
      0.4 microm, accessible for standard optical lithography.

PMID- 14682621
TI  - Pleiotropic effects of suppressing deoxyhypusine synthase expression in
      Arabidopsis thaliana.
AB  - A full-length cDNA clone encoding deoxyhypusine synthase (DHS) was isolated from
      a cDNA expression library prepared from senescing leaves of Arabidopsis thaliana.
      Southern blot analysis indicated that DHS is encoded by a single-copy gene in
      Arabidopsis. During leaf development, the abundance of DHS mRNA in the third pair
      of rosette leaves peaked at days 14 and 35 after emergence coincident with the
      initiation of bolting and the later stages of leaf senescence, respectively.
      These changes in DHS expression were paralleled by corresponding changes in
      transcript abundance for eIF-5A1, one of three isoforms of eIF-5A in Arabidopsis.
      Levels of DHS transcript also increased in detached leaves coincident with post
      harvest senescence. DHS was suppressed in transgenic plants by introducing
      antisense full-length or 3'-untranslated Arabidopsis DHS cDNA under the
      regulation of the constitutive cauliflower mosaic virus (CaMV-35S) promoter.
      Plants expressing the antisense transgenes had reduced levels of leaf DHS protein
      and, depending on the level of DHS suppression, exhibited delayed natural leaf
      senescence, delayed bolting, increased rosette leaf and root biomass, and
      enhanced seed yield. Suppression of DHS also delayed premature leaf senescence
      induced by drought stress resulting in enhanced survival in comparison with wild
      type plants. In addition, detached leaves from DHS-suppressed plants exhibited
      delayed post-harvest senescence. These pleiotropic effects of DHS suppression
      indicate that the protein plays a central role in plant development and
      senescence.

PMID- 14682623
TI  - High-Q whispering modes in empty spherical cavity resonators.
AB  - This work presents the study of high-order modes in spherical cavity resonators.
      In general there are resonant mode families, degenerate in frequency, that
      "whisper" around the spherical surface. We call these whispering spherical (WS)
      mode sets. Each set includes the well-known whispering gallery (WG) mode, which
      propagates like a ray around the azimuth. Also, we identify a new mode, which we
      label the whispering longitudinal (WL) mode. This mode propagates as a wave front
      along the longitudinal direction. The rest of the degenerate set propagates like
      a combination of the WG and WL modes. We show that transverse electric WS modes
      have high geometric factors, greater than 2000, which increase linearly with
      frequency. This is an order of magnitude greater than that of a TM010 cylindrical
      resonator. Also, Q-factors as high as 65,000 at 13.3 GHz were measured at room
      temperature.

PMID- 14682624
TI  - Ultimate linewidth reduction of a semiconductor laser frequency-stabilized to a
      Fabry-Perot interferometer.
AB  - We report a theoretical dynamical analysis on effect of semiconductor laser phase
      noise on the achievable linewidth when locked to a Fabry-Perot cavity fringe
      using a modulation-demodulation frequency stabilization technique such as the
      commonly used Pound-Drever-Hall frequency locking scheme. We show that, in the
      optical domain, the modulation-demodulation operation produces, in the presence
      of semiconductor laser phase noise, two kinds of excess noise, which could be
      much above the shot noise limit, namely, conversion noise (PM-to-AM) and
      intermodulation noise. We show that, in typical stabilization conditions, the
      ultimate semiconductor laser linewidth reduction can be severely limited by the
      intermodulation excess noise. The modulation-demodulation operation produces the
      undesirable nonlinear intermodulation effect through which the phase noise
      spectral components of the semiconductor laser, in the vicinity of even multiples
      of the modulation frequency, are downconverted into the bandpass of the frequency
      control loop. This adds a spurious signal, at the modulation frequency, to the
      error signal and limits the performance of the locked semiconductor laser. This
      effect, reported initially in the microwave domain using the quasistatic
      approximation, can be considerably reduced by a convenient choice of the
      modulation frequency.

PMID- 14682625
TI  - New phase-noise model for crystal oscillators: application to the Clapp
      oscillator.
AB  - Leeson's is the basic model for predicting oscillator noise. A mathematical
      analysis of this "heuristic" model has been proposed. Both models do not detail
      the relative importance of the amplifier transfer function associated to its own
      noise with regard to that of the resonator. In this paper, an improved version of
      those previous models is presented. The phase noise generated by the amplifier
      and the one generated by the resonator are differentiated without considering
      their origins, such as the conversion of amplitude modulation noise into phase
      modulation noise. The power spectral densities of phase noise at various points
      of the oscillator loop are calculated from their respective correlation
      functions. As a consequence, the influence of the inner amplifier and resonator
      noises on the resulting oscillator noise is predictable. The model is especially
      attractive to the makers of widely used quartz oscillators. The resulting
      oscillator noise is easily obtained from the oscillator open-loop noise. An
      example of the phase-noise modeling of the Clapp quartz crystal oscillator is
      simulated and discussed.

PMID- 14682626
TI  - Novel modeling technique for the stator of traveling wave ultrasonic motors.
AB  - Traveling wave ultrasonic motors (TWUM) are a promising type of piezoelectric
      transducers, which are based on the friction transmission of mechanical
      propagating waves. These waves are excited on the stator by using high Q
      piezoelectric ceramics. This article presents a modeling strategy, which allows
      for a quick and precise modal and forced analysis of the stator of TWUM. First
      order shear deformation laminated plate theory is applied to annular subdomains
      (super-elements) of the stator. In addition to shear deformations, the model
      takes into account the effect of rotary inertia, the stiffness contribution of
      the teeth, and the linear varying thickness of the stator. Moreover, the
      formulation considers a more realistic function for the electric field inside the
      piezoelectric ceramic, i.e., a linear function, instead of the generally assumed
      constant electric field. The Ritz method is used to find an approximated solution
      for the dynamic equations. Finally, the modal response is obtained and compared
      against the results from classical simplified models and the finite element
      method. Thus, the high accuracy and short computation times of the novel strategy
      were demonstrated.

PMID- 14682627
TI  - A corrected modal representation of thickness vibrations in quartz plates and its
      influence on the transversely varying case.
AB  - A modal representation of the thickness vibrations of rotated Y-cut quartz
      plates, which was used in the treatment of driven transversely varying thickness
      modes, is shown to be defective in certain respects. The differential equations
      and edge conditions for transversely varying thickness modes have been used in
      the accurate treatment of trapped energy resonators, monolithic crystal filters,
      and contoured quartz resonators, even though those defects were present. In this
      work those defects in the thickness solution are corrected along with the
      influence on the differential equations and edge conditions in the transversely
      varying case. The corrected modal representation shows that, because in practical
      applications to the above mentioned devices, the driving frequency is always near
      a thickness resonant frequency, essentially the same results will be obtained
      with the corrected representation as were obtained with the defective one, which
      explains why the results obtained with the defective equations were so accurate.

PMID- 14682628
TI  - Eccentricity effects on acoustic radiation from a spherical source suspended
      within a thermoviscous fluid sphere.
AB  - Acoustic radiation from a spherical source undergoing angularly periodic
      axisymmetric harmonic surface vibrations while eccentrically suspended within a
      thermoviscous fluid sphere, which is immersed in a viscous thermally conducting
      unbounded fluid medium, is analyzed in an exact fashion. The formulation uses the
      appropriate wave-harmonic field expansions along with the translational addition
      theorem for spherical wave functions and the relevant boundary conditions to
      develop a closed-form solution in form of infinite series. The analytical results
      are illustrated with a numerical example in which the vibrating source is
      eccentrically positioned within a chemical fluid sphere submerged in water. The
      modal acoustic radiation impedance load on the source and the radiated far-field
      pressure are evaluated and discussed for representative values of the parameters
      characterizing the system. The proposed model can lead to a better understanding
      of dynamic response of an underwater acoustic lens. It is equally applicable in
      miniature transducer analysis and design with applications in medical
      ultrasonics.

PMID- 14682629
TI  - Unit-delay focusing architecture and integrated-circuit implementation for high
      frequency ultrasound.
AB  - High-frequency ultrasound (above 10 MHz) has been used successfully in many
      medical applications, including eye, skin, gastrointestinal, intravascular, and
      Doppler flow imaging. Most of these applications use single-element transducers,
      thereby imposing a tradeoff between resolution and depth of field. Fabrication
      difficulties and the need for high-speed electronic beamformers have prevented
      widespread use of arrays at high frequencies. In this paper, a unit-delay
      focusing architecture suitable for use with high-frequency ultrasound annular
      arrays is described. It uses a collection of identical, active delay cells that
      may be simultaneously varied to accomplish focusing. Results are presented for an
      analog integrated circuit intended for use with a five-element, 50-MHz planar
      annular array. Focusing is possible over an axial range for which the ratio of
      maximum to minimum f-number is 2.1. Unit-delay architectures also are described
      for curved annular arrays and linear arrays.

PMID- 14682630
TI  - Application of ultrasound-based velocity estimate statistics to strain-rate
      estimation.
AB  - Quantification of the relative myocardial deformation rate, or strain rate, is an
      emerging capability to aid a cardiologist in assessing myocardial function.
      Ultrasound Doppler techniques can be used to compute tissue motion relative to a
      transducer. The myocardial strain rate can be computed as the localized spatial
      derivative of the tissue velocity. Such a strain-rate estimate is typically
      numerically noisy. We present the relevant speckle statistics to faciliate the
      computation of the strain rate based on a weighted least squares regression, with
      statistically appropriate weights.

PMID- 14682631
TI  - Ultrasound characterization of coronary artery wall in vitro using temperature
      dependent wave speed.
AB  - Temperature dependence of the speed of sound, partial partial differential
      c/partial partial differential T, is examined as a parameter to characterize
      tissue-equivalent phantoms and coronary artery tissue in vitro. The experimental
      system comprises an ultrasound biomicroscope, operating at center frequency of 50
      MHz, and a temperature controlled micropositioning sample cell. Radio frequency
      (RF) backscattered signals were recorded, with a digital oscilloscope, from 64
      independent positions and at 5 temperatures starting at 31 degrees C (phantom)
      and 36 degrees C (tissue) in steps of one degree. Time shift per degree Celsius
      (delta t/delta T) was obtained with a correlation technique applied between gated
      sections of two RF-signals collected with one degree temperature difference from
      the same location in the sample. The average (delta t/delta T), calculated for
      every position of the gated sections along the propagation axis of the ultrasound
      beam, has the slope proportional to the difference between the linear coefficient
      of thermal expansion and the thermal sensitivity of the speed of sound.
      Calibration measurements of partial partial differential c/partial partial
      differential T, made with single- and three-layer tissue equivalent phantoms,
      correlated well (r > or = 0.91) with those measured by the time-of-flight
      substitution method. The partial partial differential c/partial partial
      differential T was estimated for the three layers on the wall of eight samples of
      human coronary arteries, obtained at autopsy from four individuals. The partial
      partial differential c/partial partial differential T for the intima layers
      decreases as the disease progresses from mild intimal thickening to a more
      advanced atherosclerosis.

PMID- 14682632
TI  - Modeling of anomalies due to hydrophones in continuous-wave ultrasound fields.
AB  - Needle and spot-poled membrane hydrophones using polyvinylidene fluoride (PVDF)
      sensors are widely used for characterization of biomedical ultrasound fields. It
      is known that, in measurements of continuous-wave (CW) fields, standing waves may
      be generated between the transducer and the hydrophone, distorting the field and
      possibly alternating the signal of the hydrophone. This study uses a three
      dimensional, full-wave method to computationally simulate the distortion in the
      CW field caused by needle and membrane hydrophones. The physical model used in
      simulations is based on the linear time-harmonic wave equation, which therefore
      neglects the effects of nonlinear wave propagation. The significance of the
      distortion is examined by comparing fields emitted by 0.5-5.0 MHz planar circular
      transducers in the absence and presence of the hydrophones. In addition, the
      effect of the field distortions on the signal of the hydrophones is studied with
      simulated measurements. The simulations showed an observable standing wave
      pattern between the source and the needle hydrophone if the diameter of the
      needle was larger than a half of the wavelength. However, the standing waves had
      no clear effect on the signal of the hydrophone. The presence of membrane
      hydrophone in the CW field generated notable standing waves. Furthermore, the
      standing waves caused a periodic distortion to the signal of the membrane
      hydrophone.

PMID- 14682633
TI  - A power transducer system for the ultrasonic lubrication of the continuous steel
      casting.
AB  - A critical point in the continuous steel casting process exists in the meniscus
      zone of the cooled mould, i.e., the region in which the steel stream flowing out
      of the tundish nozzle starts to solidify. This is a critical point because of the
      sticking that occurs between the solid shell of steel and the mould. In this
      work, a new system for the ultrasonic lubrication of the continuous steel casting
      is proposed and experimentally tested. The basic idea is to excite one of the
      mould's natural vibration modes by means of a distributed ultrasonic source. This
      source is composed of an array of power emitters, with each of them placed upon
      an antinode of the mould. An experimental characterization of the vibrational
      behavior of a square mould was first carried out. The most active resonance modes
      of the mould were detected with an experimental technique based on a simple
      impedance measurement. The modal shape of the selected mode, and hence the
      position of antinodes, was obtained by means of interferometer measurements.
      Additional experimental investigations were performed by exciting mould
      vibrations with up to four piezoceramic disks placed on different sets of
      antinodes. Some positioning criteria to maximize the superposition effect were
      derived. Measurements were obtained through excitation of the mould with up to
      four Langevin-type power emitters, designed and manufactured to work at the
      mould's selected resonance frequency. These measurements have shown that, by
      increasing the number of emitters, the ultrasonic power transmitted to the mould
      and, consequently, the maximum available displacement, increases. Other practical
      advantages of the proposed system are highlighted and discussed.

PMID- 14682634
TI  - Through-transmission imaging of solids in air using ultrasonic gas-jet
      waveguides.
AB  - An ultrasonic waveguide has been produced in air by using a gas jet. This uses
      the fact that a lower acoustic velocity can be produced within the jet, relative
      to the air surrounding it. The lower velocity is achieved by mixing carbon
      dioxide with air within the jet at a concentration that is a compromise between
      lower acoustic velocity and increasing attenuation. Using a capacitance
      transducer placed within the flowing gas, it is shown that improvements in the
      beam width can result when the gas jet is used. Air-coupled images of solid
      samples have been produced in through transmission, which demonstrate that an
      improved lateral resolution can result when a comparison is made to images from
      conventional air-coupled testing.

PMID- 14682635
TI  - High-resolution, air-coupled ultrasonic imaging of thin materials.
AB  - This paper describes the use of a focused air-coupled capacitance transducer
      combined with pulse compression techniques to form high-resolution images of thin
      materials in air. The focusing of the device is achieved by using an off-axis
      parabolic mirror. The lateral resolution of the focused transducer, operating
      over a bandwidth of 1.2 MHz, was found to be less than 0.5 mm. A combination of
      the focused transducer as a source and a planar receiver in through-transmission
      mode has been developed for the measurement of different features in paper
      products, with a lateral resolution in through-transmission imaging of
      approximately 0.4 mm. Images in air of thin samples such as bank notes, high
      quality writing paper, stamps, and sealed joints were obtained without contact to
      the sample.

PMID- 14682636
TI  - Modeling of received signals from annular array ultrasound transducers due to
      extended reflectors.
AB  - This paper describes a computationally efficient numerical technique for
      calculating the received signal from a broadband annular array transducer
      operating in pulse-echo mode, due to a specified reflector. The technique is
      referred to as the Diffraction Response from Extended Area Method (DREAM) and
      operates by tessellating the reflector into planar tiles with a dimension of
      several wavelengths (at the highest frequency of interest) and finding the
      contribution from a given tile by a temporal low-pass filtering rather than
      spatial integration. In particular, this paper formulates the theory for the
      DREAM for tessellation into triangular tiles and demonstrates the improved
      performance with triangular tiles relative to square tiles. This paper also
      analyzes the mean square error of the received signal as a function of the
      diameters of the transmitting and the receiving transducers and the radial
      position and orientation of the tile. Based on this, a set of rules for the
      optimal tile size is developed. The power of the modeling technique is
      demonstrated by calculating the received signal from an annular array transducer
      due to three given extended reflectors in which the effect of the focal point
      location on the received signal is readily demonstrated.

PMID- 14682637
TI  - SAW COM-parameter extraction in AlN/diamond layered structures.
AB  - Highly c-axis oriented aluminum nitride (AlN) thin piezoelectric films have been
      grown on polycrystalline diamond substrates by pulsed direct current (DC)
      magnetron reactive sputter-deposition. The films were deposited at a substrate
      temperature below 50 degrees C (room temperature) and had a typical full width
      half maximum (FWHM) value of the rocking curve of the AlN-002-peak of 2.1
      degrees. A variety of one-port surface acoustic wave (SAW) resonators have been
      designed and fabricated on top of the AlN films. The measurements indicate that
      various SAW modes are excited. The SAW phase velocities of up to 11.800 m/s have
      been measured. These results are in agreement with calculated dispersion curves
      of the AlN/diamond structure. Finally, the coupling of modes parameters have been
      extracted from S11 measurements using curve fitting for the first SAW mode, which
      indicate an effective coupling K2 of 0.91% and a Q factor of about 600 at a
      frequency of 1050 MHz.

PMID- 14682638
TI  - Design of efficient, broadband single-element (20-80 MHz) ultrasonic transducers
      for medical imaging applications.
AB  - This paper discusses the design, fabrication, and testing of sensitive broadband
      lithium niobate (LiNbO3) single-element ultrasonic transducers in the 20-80 MHz
      frequency range. Transducers of varying dimensions were built for an f# range of
      2.0-3.1. The desired focal depths were achieved by either casting an acoustic
      lens on the transducer face or press-focusing the piezoelectric into a spherical
      curvature. For designs that required electrical impedance matching, a low
      impedance transmission line coaxial cable was used. All transducers were tested
      in a pulse-echo arrangement, whereby the center frequency, bandwidth, insertion
      loss, and focal depth were measured. Several transducers were fabricated with
      center frequencies in the 20-80 MHz range with the measured -6 dB bandwidths and
      two-way insertion loss values ranging from 57 to 74% and 9.6 to 21.3 dB,
      respectively. Both transducer focusing techniques proved successful in producing
      highly sensitive, high-frequency, single-element, ultrasonic-imaging transducers.
      In vivo and in vitro ultrasonic backscatter microscope (UBM) images of human eyes
      were obtained with the 50 MHz transducers. The high sensitivity of these devices
      could possibly allow for an increase in depth of penetration, higher image signal
      to-noise ratio (SNR), and improved image contrast at high frequencies when
      compared to previously reported results.

PMID- 14682639
TI  - Broadband ultrasonic transducers using a LiNbO3 plate with a ferroelectric
      inversion layer.
AB  - Some heat treatment of a lithium niobate (LiNbO3) plate induces domain inversion,
      thereby yielding a ferroelectric inversion layer. In such a piezoelectric plate
      with an inversion layer, even-order thickness-extensional modes, as well as odd
      order modes, can be excited piezoelectrically. Therefore, the ultrasonic
      transducer using such a piezoelectric plate is expected to operate over a wide
      frequency range. In this paper, it is shown that broadband ultrasonic transducers
      can be obtained at a certain thickness ratio of inversion layer to plate, and
      that the transducer characteristics differ depending on whether the inversion
      layer is on the front side or on the backside. The broadband characteristics are
      experimentally demonstrated by fabricating transducers with 9 MHz or 75 MHz
      center frequency using 36 degrees rotated Y-cut LiNbO3 plates with a
      ferroelectric inversion layer.

PMID- 14682640
TI  - An asymptotic theory for vibrations of inhomogeneous/laminated piezoelectric
      plates.
AB  - An asymptotic theory for the vibration analysis of inhomogeneous monoclinic
      piezoelectric plates is developed by using small parameter expansion. The theory
      includes the important special case of a laminated plate in which each layer is
      homogeneous and orthotropic, but distinct from the other layers by having a
      different material or a different orientation. A hierarchy of two-dimensional
      equations of the same homogeneous operator for each order is reduced from the
      three-dimensional framework of linear piezoelectricity. The elasticity version of
      the leading-order equation is the same as that of the classical Kirchhoff
      inhomogeneous plate theory and, therefore, is easily solvable. By contrast, it is
      not straightforward to find solutions of the higher-order equations. The
      solvability condition is thus established for this purpose, by which higher-order
      frequency parameters are derived. The present theoretical formulation is examined
      by comparing the present asymptotic results with an exact three-dimensional
      solution for a piezoelectric bimorph strip, and excellent agreement is reached.
      Some new results are presented.

PMID- 14682641
TI  - Capacitive micromachined ultrasonic transducers with diffraction-based integrated
      optical displacement detection.
AB  - Capacitive detection limits the performance of capacitive micromachined
      ultrasonic transducers (CMUTs) by providing poor sensitivity below megahertz
      frequencies and limiting acoustic power output by imposing constraints on the
      membrane-substrate gap height. In this paper, an integrated optical
      interferometric detection method for CMUTs, which provides high displacement
      sensitivity independent of operation frequency and device capacitance, is
      reported. The method also enables optoelectronics integration in a small volume
      and provides optoelectronic isolation between transmit and receive electronics.
      Implementation of the method involves fabricating CMUTs on transparent substrates
      and shaping the electrode under each individual CMUT membrane in the form of an
      optical diffraction grating. Each CMUT membrane thus forms a phase-sensitive
      optical diffraction grating structure that is used to measure membrane
      displacements down to 2 x 10(-4) A/square root(Hz) level in the dc to 2-MHz
      range. Test devices are fabricated on quartz substrates, and ultrasonic array
      imaging in air is performed using a single 4-mm square CMUT consisting of 19 x 19
      array of membranes operating at 750 kHz.

PMID- 14682642
TI  - Volumetric ultrasound imaging using 2-D CMUT arrays.
AB  - Recently, capacitive micromachined ultrasonic transducers (CMUTs) have emerged as
      a candidate to overcome the difficulties in the realization of 2-D arrays for
      real-time 3-D imaging. In this paper, we present the first volumetric images
      obtained using a 2-D CMUT array. We have fabricated a 128 x 128-element 2-D CMUT
      array with through-wafer via interconnects and a 420-microm element pitch. As an
      experimental prototype, a 32 x 64-element portion of the 128 x 128-element array
      was diced and flip-chip bonded onto a glass fanout chip. This chip provides
      individual leads from a central 16 x 16-element portion of the array to
      surrounding bondpads. An 8 x 16-element portion of the array was used in the
      experiments along with a 128-channel data acquisition system. For imaging
      phantoms, we used a 2.37-mm diameter steel sphere located 10 mm from the array
      center and two 12-mm-thick Plexiglas plates located 20 mm and 60 mm from the
      array. A 4 x 4 group of elements in the middle of the 8 x 16-element array was
      used in transmit, and the remaining elements were used to receive the echo
      signals. The echo signal obtained from the spherical target presented a frequency
      spectrum centered at 4.37 MHz with a 100% fractional bandwidth, whereas the
      frequency spectrum for the echo signal from the parallel plate phantom was
      centered at 3.44 MHz with a 91% fractional bandwidth. The images were
      reconstructed by using RF beamforming and synthetic phased array approaches and
      visualized by surface rendering and multiplanar slicing techniques. The image of
      the spherical target has been used to approximate the point spread function of
      the system and is compared with theoretical expectations. This study
      experimentally demonstrates that 2-D CMUT arrays can be fabricated with high
      yield using silicon IC-fabrication processes, individual electrical connections
      can be provided using through-wafer vias, and flip-chip bonding can be used to
      integrate these dense 2-D arrays with electronic circuits for practical 3-D
      imaging applications.

PMID- 14682643
TI  - Compressibility of nano inclusions in complex fluids by ultrasound velocity
      measurements.
AB  - We present a high precision ultrasonic velocimeter for a small volume sample (1
      cm3) for a path length of 1 cm achieved. The method used is based on the time of
      flight measurement with an original signal processing technique: the barycenter
      method. With our system, we have measured the sound velocity with an accuracy of
      10(-5). The detection of a difference in velocity between two liquids of about 2
      cm/s is achieved. The compressibility of the reference liquid can then be deduced
      with an accuracy better than 0.2%. Using this custom-made system, we have studied
      and characterized complex fluids, systems biomimetic of biological membranes, as
      well as proteins included in nanometric water droplets. Under these experimental
      conditions, we have reached the value of protein compressibilities with an
      accuracy better than 10%.

PMID- 14682644
TI  - Patterns of fluoride intake from 36 to 72 months of age.
AB  - OBJECTIVES: This paper reports on estimated daily fluoride intake from water by
      itself, beverages, selected foods, dentifrice, and dietary supplements, both
      individually and combined (mg and mg F/kg bw), among 785 children in the Iowa
      Fluoride Study from 36 to 72 months of age. METHODS: Children were recruited in
      1992-95, with questionnaires sent at four- to six-month intervals. Dietary
      fluoride intake estimates used community and individual water fluoride levels and
      average fluoride levels of beverages and foods prepared with water. Descriptive
      statistics and generalized linear models (GLM) assessed levels and associations
      with demographic factors. RESULTS: There was substantial variation in fluoride
      intake, with some individuals' intakes greatly exceeding the means. Daily water
      fluoride intake estimates (in mg) increased with age, fluoride intake from other
      beverages and dentifrice both decreased slightly, and combined intake was quite
      consistent. For combined intake per unit body weight (mg F/kg bw), there was a
      steady decline with age. Therefore, the percentages with estimated intake
      exceeding possible thresholds for dental fluorosis also declined with age.
      CONCLUSIONS: Daily mean fluoride intakes from single and combined sources are
      relatively stable from 36-72 months of age among these children.

PMID- 14682645
TI  - Clinical evaluation of three restorative materials applied in a minimal
      intervention caries treatment approach.
AB  - OBJECTIVES: This paper reports on a longitudinal evaluation of three materials
      (glass ionomer, zinc oxide-eugenol cement, and composite) employed in a minimal
      restorative intervention approach of 81 high caries-active pregnant women
      selected for a preventive oral health program in Brazil. The aim of the study was
      to evaluate the clinical behavior of the glass ionomer cement, currently
      indicated in programs for control of carious lesions. METHODS: The patients were
      randomly divided into two groups. Both groups were engaged in an oral health
      promotion approach. In Group 1, 417 glass ionomer restorations were placed in 43
      individuals, involving all types and sizes of cavities. In the second group, 213
      posterior zinc oxide-eugenol (ZOE) restorations and 127 anterior composite
      restorations were placed in 38 patients. Minimal cavity preparations were made,
      in which only soft or infected dentin was removed, on the basis of clinical
      judgment. RESULTS: After two years, the restorations were clinically evaluated by
      two examiners for marginal integrity, amount of wear, presence of fracture,
      carious lesions, and lost restorations. Statistical analysis (chi-square test)
      identified statistically significant difference between glass ionomer and ZOE
      (90.6% vs 9.2%). Comparing glass ionomer and composite, similar survival rates
      were observed. The success rate observed for the glass ionomer cement ranged from
      77.1 percent to 92.5 percent, depending on the type and size of cavity in which
      it was applied. Four teeth restored with glass ionomer cement and one tooth
      restored with composite showed caries signs. Regarding the ZOE restorations,
      caries was always associated with other causes of failure such as excessive wear,
      restoration loss, or marginal defects, with no possibility of separate
      evaluation. Despite the preventive and therapeutic measurements employed, a mean
      increase of 2.15 new surfaces with cavities was observed in Group 1, as well as
      2.83 surfaces presenting the same status in Group 2. CONCLUSIONS: This study
      demonstrated that highly viscous glass ionomer cement applied in a minimal
      intervention approach provided high-quality preventive and restorative care after
      two years to a population at high risk for caries. The composite was employed in
      cavities exposed to lower stress, such as in the anterior teeth, and its behavior
      was comparable to that of the glass ionomer cement. The reinforced ZOE presented
      a high failure rate, thus contraindicating its use for such purpose.

PMID- 14682646
TI  - The dynamics of toothache pain and dental services utilization: 24-month
      incidence.
AB  - OBJECTIVES: The aims of this study were twofold: (1) to describe patterns of
      change in reported toothache pain, and (2) to examine the impact of toothache
      pain on dental care utilization and vice versa. METHODS: Data from the Florida
      Dental Care Study (FDCS), a longitudinal study of oral health and dental service
      utilization conducted in north Florida, were used to measure self-reported
      toothache pain among dentate adults at baseline and four subsequent times during
      a 24-month period. Only persons 45 years of age or older with at least one
      remaining natural tooth at baseline were eligible. A total of 873 subjects
      participated, 764 of whom participated through 24 months. The analysis is focused
      on modeling transitions in the reported experience of toothache pain during
      intervals of six months. RESULTS: At the time of the baseline interview, 11.5
      percent of subjects reported current toothache pain. During subsequent six
      monthly interviews, from 13.4 percent to 21.6 percent of subjects reported having
      experienced toothache pain during the prior six-month interval. Among those with
      no toothache pain at baseline (n = 772), 31.2 percent experienced toothache pain
      at some time during the 24-month study period. The six-month incidence
      probability reflects the likelihood of developing toothache pain by estimating
      the conditional probability of reporting a toothache in a later interval given
      that this problem was not reported in the earlier one (for consecutive pairs of
      intervals). Overall, the six-month incidence probability for toothache pain in
      this study was. 11. Significantly higher 24-month incidence was observed for
      African-American subjects, those with less formal education, those in poorer
      financial circumstances, and problem-oriented dental attenders. CONCLUSIONS: In
      this diverse sample of adults, toothache pain occurs frequently and is quite
      variable overtime. Toothache occurs in conjunction with various forms of self
      reported oral disease (e.g., abscess, cavities) or tissue damage (e.g., loose
      tooth, broken tooth, bleeding gums). Subjects who experience toothache are
      slightly more likely than others to utilize dental services in the time period
      proximate to the toothache pain.

PMID- 14682647
TI  - Oral health of Bangladeshi women tobacco-with-paan users and self-reported oral
      pain following tobacco cessation.
AB  - OBJECTIVES: The study objectives were to assess the oral health status of a
      sample of UK resident Bangladeshi women tobacco-in-paan users and its
      relationship to participant age and number of daily paan, to determine the
      prevalence of oral pain at baseline and at the one-week postcessation follow-up,
      and to explore the relationship between oral health status and changes in self
      reported oral pain at baseline and at the one-week postcessation follow-up.
      METHODS: Interviews were conducted in Sylheti using fully structured
      questionnaires and an oral examination was carried out. A quit date was set and
      nicotine replacement therapy patches (Nicorette 15 mg, Pfizer) were supplied.
      Age, number of daily paan, and oral pain characteristics, including intensity,
      frequency, any provoking factors, and associated symptoms were recorded. Oral
      mucosal lesions (OMLs) and numbers of teeth decayed, missing, filled, and those
      with recession, abrasion, loss of attachment (LOA), and tooth wear were charted.
      RESULTS: Fifty-two women took part. The mean age was 42.8 years and number of
      daily paan with tobacco was 13. Compared to those aged 18-39 years, those aged 40
      years and older had poorer oral health. Older adults were significantly more
      likely to have higher numbers of teeth with recession, abrasion, and LOA greater
      than 3.5 mm. They were significantly more likely to have an OML at baseline. The
      prevalence of self-reported oral pain was 26.9 percent at baseline and 51.9
      percent at one-week follow-up. Presence of an OML at baseline was a significant
      predictor of reports of oral pain at the one-week follow-up. Results of stepwise
      multiple regression analysis confirmed this finding (OR = 3.66; 95% CI = 1.06,
      12.621; P = .04). CONCLUSIONS: Reports of oral pain at follow-up during a tobacco
      cessation program correlate with the presence of OMLs at baseline. Further
      investigation of this relationship is needed. Access to appropriate dental care,
      as an aid to successful tobacco cessation, is indicated.

PMID- 14682648
TI  - Implementing a community-based oral health care program: lessons learned.
AB  - OBJECTIVES: The objective of this paper is to report key findings of a process
      evaluation that may be useful to other institutions seeking to implement a
      community-based oral health care program primarily targeting children in dentally
      underserved communities. By partnering with community-based organizations, public
      schools, and community health care providers, the Columbia University School of
      Oral and Dental Surgery (SDOS) established the Community DentCare Network
      (DentCare) in the Harlem and Washington Heights/Inwood neighborhoods of northern
      Manhattan. These low-income neighborhoods are characterized by poor oral health
      and have been designated by the federal government as health professions shortage
      areas. METHODS: The method used in the process evaluation was open-ended
      qualitative interviewing by a sociologist with extensive experience in this
      methodology aided by a participant-observer within the DentCare program. RESULTS:
      The heterogeneity of the two communities required different strategies and
      resources to gain trust and acceptance. Fundamental changes were required of SDOS
      over a 10-year period, beginning with prioritizing community service into a
      primary mission. Collaborating with medical clinics facilitated the
      implementation of the network when the partners shared the same philosophical
      goals. Faculty and staff with different skills were needed during the start-up
      and the sustained development phases of the program.

PMID- 14682649
TI  - Associations between occupational health behaviors and occupational dental
      erosion.
AB  - OBJECTIVES: The aim of this study was to evaluate the associations between
      occupational health behaviors and occupational dental erosion. METHODS: Using
      data for 943 workers among 34 factories, selected by three-stage stratified
      cluster sampling from 888 factories using acids, two sets of modified case
      control studies were performed. The cases were 242 workers with any dental
      erosion (G1-5) and 78 with severe dental erosion (G3-5); the controls were 701
      workers with no erosion (GO) and 864 workers with no or mild erosion grades, GO
      2, respectively. The main explanatory variables were behaviors such as wearing a
      respiratory mask and gargling at work. The results were adjusted for employment,
      age, sex, knowledge, and opinion about occupational health, attrition, and
      abrasion. Bivariate and multivariate logistic regression analyses were conducted.
      RESULTS: The odds of overall occupational dental erosion (G1-5) was 0.63 (95% CI
      = 0.42, 0.94) for respiratory mask wearers compared to nonwearers; the odds of
      severe occupational dental erosion (G3-5) was not significantly less in
      respiratory mask wearers (OR = 0.94; 95% CI = 0.53, 1.67). Gargling did not show
      a significant association with occupational dental erosion in this study.
      CONCLUSIONS: Among occupational health behaviors, wearing personal protective
      respiratory masks in work was significantly associated with less overall
      occupational dental erosion.

PMID- 14682650
TI  - Relationship between oral health behaviors and general health behaviors in a
      Japanese adult population.
AB  - OBJECTIVE: The aim of this study was to analyze the relationship between oral
      health behaviors and general health behaviors in adults. METHODS: A total of
      2,467 adults (1,208 men and 1,259 women aged 20-59 years) who consulted dentists
      in Chiba City were administered a questionnaire. RESULTS: Women, older
      participants, and those living with family had better health behaviors than the
      other subjects studied. Additive indices for oral and general health behaviors
      were significantly correlated. Toothbrushing frequency was significantly
      correlated with five items of general health behavior (smoking, drinking,
      exercise, eating breakfast, and having medical check-ups). Having dental check
      ups was significantly correlated with having medical check-ups. There was a
      negative correlation between dental flossing and drinking. CONCLUSIONS: Of all
      oral health behaviors examined, toothbrushing frequency was the most predictive
      indicator of general health behavior.

PMID- 14682651
TI  - Evaluation of a dental health education program for midwives.
AB  - OBJECTIVE: The aim of the present study was to evaluate the effect of a dental
      health program for the midwives in primary health care services in Izmir, Turkey.
      METHODS: One hundred sixty-four midwives participated in the pilot project. The
      program was evaluated by quantitative and qualitative methods. The quantitative
      method assessed the improvement of the dental knowledge level, whereas the
      qualitative method was conducted to determine the assessments of the
      participants. RESULTS: The percentages of correct responses given to knowledge
      items were higher after the program. The midwives defined their role as an
      important first step for dental services. Education atmosphere was the best
      characteristic of the program, whereas lack of a written document was an
      important limitation. CONCLUSION: Despite some limitations, the program was an
      effective way of improving the oral health knowledge of the midwives and their
      motivation for dental services.

PMID- 14682652
TI  - Report of recommendations from the National Dental Public Health Workshop,
      February 10-12, 2002, Bethesda, MD.
AB  - A two-and-a-half day workshop was held beginning February 10, 2002, to review the
      current state of dental public health training in the United States with the aim
      of creating recommendations that would address identified problems and lead to
      improvements in the quality of dental public health training. This workshop, held
      in Bethesda, Maryland, was sponsored by the Health Resources and Services
      Administration (HRSA) through a contract with the American Association of Public
      Health Dentistry (AAPHD). Workshop invitees included the program directors of all
      accredited dental public health residency programs in the United States and
      Canada, selected dental public health residents, and additional consultants
      invited based on their expertise in dental public health education. The
      recommendations have been placed into three categories: training, financing, and
      workforce development. Along with background and process summaries, these
      recommendations are reported here.

PMID- 14682653
TI  - Performance of double acid-etched surface external hex titanium implants in
      relation to one- and two-stage surgical procedures.
AB  - BACKGROUND: The use of external hex titanium implants is widely accepted;
      however, in the past few years, they have been placed by using not only the
      traditional two-stage surgical protocol, but also the one-stage surgical
      protocol. The aim of the present study was to compare the success rates that can
      be obtained from two-stage surgeries (conventional protocol) and one-stage
      surgeries when double acid-etched surface external hex titanium implants are
      used. METHODS: A total of 654 double acid-etched surface external hex titanium
      implants were studied in 195 patients (109 females and 86 males) aged 18 to 79
      (mean 49.20). These patients were followed-up both clinically and
      radiographically for 3 years. Among these implants, 338 were inserted by means of
      two-stage surgery and 316 were placed following the one-stage surgery protocol.
      RESULTS: The success rate of the whole sample of double acid-etched surface
      implants was 99.23%. The results showed a 99.05% success rate for one-stage
      surgeries and 99.40% rate for two-stage surgeries. Only three of the implants
      inserted by performing one-stage surgery and two of the implants placed using two
      stage surgery failed before they were loaded. No implants were lost after the
      loading was completed. The bone level at 12 months was 0.58 mm for one-stage
      placed implants and 0.54 mm for two-stage-placed implants. At 24 months the bone
      level was 0.77 mm and 0.68, respectively, and at 36 months 0.89 and 0.83.
      CONCLUSION: The similar and high success rates obtained in one- and two-stage
      surgeries using double acid-etched surface external hex titanium implants
      demonstrate that it is possible to choose the most convenient surgical procedure
      for each particular case without increasing the risk of failure.

PMID- 14682654
TI  - Clinical responses to mechanical periodontal treatment in Chinese chronic
      periodontitis patients with and without Actinobacillus actinomycetemcomitans.
AB  - BACKGROUND: The purpose of this study was to compare 12-month clinical responses
      to mechanical periodontal treatment in Chinese chronic periodontitis patients at
      sites with and without Actinobacillus actinomycetemcomitans at baseline, and to
      investigate the ability of mechanical periodontal treatment to eliminate A.
      actinomycetemcomitans. METHODS: Nineteen patients and a total of 76 selected
      sites with a mean probing depth (PD) of > or = 7 mm were studied. Whole mouth
      presence or absence of supragingival plaque (PI%), bleeding on probing (BOP%),
      probing depth (PD), and probing attachment level (PAL) were recorded at six sites
      per tooth at baseline and after 3, 9, and 12 months. Baseline subgingival plaque
      samples were taken from the deepest PD site in each quadrant using sterile paper
      points and were cultured on TSBV plates for 5 days in a 5% CO2-air incubator. All
      sites received mechanical periodontal treatment, which included oral hygiene
      instructions and supragingival and subgingival instrumentation with or without
      surgical access, with maintenance care being provided once every 3 months
      thereafter. RESULTS: At baseline, A. actinomycetemcomitans was isolated in 13 of
      the 19 subjects (68%) and in 29 out of the 76 sampled sites (38%). At the end of
      12 months, in three of the initially A. actinomycetemcomitans-positive subjects,
      A. actinomycetemcomitans was not detected in the sampled sites, while one
      subject, in whom A. actinomycetemcomitans was not initially found at the sampled
      sites was A. actinomycetemcomitans-positive at 12 months. Multi-level variance
      component models showed there was no statistically significant difference in all
      clinical parameters between A. actinomycetemcomitans-positive and -negative
      subjects (P > 0.05). In the sampled sites of the initially A.
      actinomycetemcomitans-positive subjects, the mean PD was reduced from 7.6 +/- 1.6
      mm to 3.2 +/- 1.8 mm, the mean PAL gain was 1.4 +/- 2.0 mm, and the mean
      recession was 3.0 +/- 2.3 mm. The corresponding figures in the sampled sites of
      the initially A. actinomycetemcomitans-negative subjects were 7.5 +/- 1.6 mm to
      2.7 +/- 1.0 mm, 2.3 +/- 2.6 mm and 2.4 +/- 2.2 mm for mean PD changes, PAL gain,
      and mean recession, respectively. CONCLUSIONS: Favorable clinical responses to
      mechanical periodontal therapy may occur in Chinese chronic periodontitis
      patients at sites infected with A. actinomycetemcomitans. The mere detection of
      subgignival A. actinomycetemcomitans does not necessarily imply poorer treatment
      outcomes in the control of chronic periodontitis.

PMID- 14682655
TI  - In vivo sensitivity of human root dentin to air blast and scratching.
AB  - BACKGROUND: The present study evaluated the prevalence of radicular sensitivity
      to scratching as well as the effects of a common oxalate desensitizing agent on
      sensitivity to air blast and scratching. METHODS: Eighty-seven patients self
      reporting dentin hypersensitivity, with at least two hypersensitive teeth, were
      included. Prior to any treatment, their sensitivity to air blast was recorded and
      rated as absent or present, and the force necessary to trigger pain when
      scratching was measured with a scratchometer in cN. For each patient one
      sensitive tooth was treated with an oxalate desensitizing agent and the other one
      with a placebo solution. The same measurements were carried out after treatment.
      RESULTS: Following treatment with a placebo solution, 70% of the teeth remained
      sensitive to air blast while only 38% of the desensitizing agent-treated teeth
      remained sensitive to air blast (P < 0.01). The mean force required to elicit
      pain prior to any treatment was 44 +/- 17 cN. This force statistically increased
      significantly after application of the placebo (53 +/- 17 cN) (P < 0.05). After
      using the desensitizing agent, the force was even higher (95 +/- 24 cN) (P <
      0.01). Only 8% of the teeth treated with the desensitizing agent did not respond
      to treatment compared to 37% of the teeth treated with the placebo solution.
      CONCLUSIONS: The placebo solution had a significant effect on sensitivity to air
      blast and to scratching (P < 0.05). The oxalate desensitizing agent was more
      effective than the placebo solution at decreasing the sensitivity both to air
      blast and to scratching (P < 0.01). The sensitivity to air blast seems to be
      overestimated because, after using the desensitizing agent, 38% of the teeth
      remained sensitive to air blast but only 8% remained sensitive to scratching.
      Pulpal inflammation may be involved in those teeth that did not respond to
      treatment.

PMID- 14682656
TI  - Formation and decontamination of biofilms in dental unit waterlines.
AB  - BACKGROUND: Biofilms are a natural occurrence in aquatic environments, including
      community drinking water systems. The interior of small-diameter tubings in
      dental unit waterlines (DUWL) are also sites of biofilm formation. In the lumen
      of the tubings, the flow is minimal, and the water becomes stagnant when the
      units are not in use. Molecules precipitate from the water onto the interior wall
      and promote the adherence of planktonic microorganisms from the water. Once they
      become sessile, the microorganisms change their phenotype. After adherence, there
      is a so-called surface-associated lag time, and the organisms then enter a growth
      phase and produce exopolysaccharides that coat the organisms in a slime layer.
      Within the biofilm, the microorganisms can signal one another, transfer
      nutrients, and exchange genetic material. The insoluble exopolysaccharides shield
      the microorganisms from displacement and from penetration by predator organisms,
      antibiotics, and disinfectants. The external surface layer of microorganisms is
      faster growing and may detach as "swarmer" cells. Detachment of microorganisms
      from dental unit biofilm flushed into the oral cavity could theoretically infect
      the patient. Splatter and aerosols from dental procedures may possibly infect
      health care personnel. METHODS: This study compared three DUWL cleaners (an
      alkaline peroxide product, a freshly mixed chlorine dioxide product, and a buffer
      stabilized chlorine dioxide product) in 16 dental units with self-contained water
      systems, 6 months after installation in a periodontal teaching clinic. One unit
      treated by flushing and drying served as a control. Units were sampled daily for
      10 days with heterotrophic plate count (HPC) sampler plates. The plates were
      incubated for 7 days at room temperature, and colonies were counted at 10.5x
      magnification. Samples of internal water tubing before and after the use of
      waterline cleaners were processed and examined by scanning electron microscopy.
      RESULTS: The estimated mean HPC was derived from original and replicate
      independent counts of two investigators of undiluted and diluted samples,
      reported as colony forming units (CFU)/ml. Shock treatments with the alkaline
      peroxide product (n = 5) reduced the HPC from baseline, but in the ratio of daily
      counts to control, there was a large variance and a trend to return of high
      counts as days passed. The mean daily HPC was significantly better than the
      control for only 3 of the 9 days of treatment and exceeded the goal of 200 on 3
      days. Freshly mixed chlorine dioxide (n = 4) and the buffer-stabilized chlorine
      dioxide (n = 5) both reduced HPC to near 0 on all days. Their ratios of daily
      estimated means to that of the control were significantly (P < 0.001) better at
      all times. In comparing treatments, the freshly mixed chlorine dioxide was better
      (P < 0.001) than the alkaline peroxide on 8 of 9 days. The buffered chlorine
      dioxide treatment was better than the alkaline peroxide at all times. The two
      chlorine dioxide treatments each had so many HPC counts of 0 that a meaningful
      statistical difference between them was not calculated. Scanning electron
      microscopy of plastic waterline tubing samples taken before and after treatments
      showed reductions in biofilm coverage, but the differences were not statistically
      significant. CONCLUSIONS: Chlorine dioxide waterline cleaners are effective in
      decontaminating DUWL biofilm. Chlorine dioxide has advantages over other chlorine
      products. Controlling DUWL biofilm may have beneficial effects on nosocomial
      infections.

PMID- 14682657
TI  - Factors associated with periodontal diseases in a dental teaching clinic
      population in northern Jordan.
AB  - BACKGROUND: A cross-sectional study of 603 subjects between 15 and 65 years of
      age (270 males and 333 females) from a dental teaching center serving a local
      population in northern Jordan was performed to identify the factors associated
      with probing depth (PD), clinical attachment level (CAL), gingival recession
      (GR), and number of missing teeth (MT). METHODS: All patients were interviewed
      orally and examined, using a structured questionnaire, by a single examiner. For
      each patient, the oral hygiene of six selected teeth and periodontal status of
      all teeth, excluding third molars, were assessed using plaque index (PI), PD,
      CAL, GR, and MT. Whole-mouth averages of PD, CAL, and GR were calculated and used
      as the outcome variables. RESULTS: Increased age, plaque index, having diabetes,
      and smoking more than 15 pack-years were significantly associated with increased
      PD, CAL, and GR. Brushing was significantly associated with decreased PD and MT,
      while brushing more than once per day was associated with increased GR. Use of
      dental floss and having hypertension were significantly associated with increased
      CAL and GR. Having peptic ulcers and having allergies were significantly
      associated with increased CAL only. CONCLUSIONS: The findings suggest that
      increased age, high plaque index, having diabetes, and smoking more than 15 pack
      years are risk indicators of periodontal diseases as assessed by PD, CAL, and GR.
      Longitudinal, intervention, and etiology-focused studies will establish whether
      these indicators are true risk factors.

PMID- 14682658
TI  - Effect of estrogen and calcitonin therapies on bone density in a lateral area
      adjacent to implants placed in the tibiae of ovariectomized rats.
AB  - BACKGROUND: This study evaluated the influence of estrogen and calcitonin
      administration on tibial bone density in a lateral area adjacent to implants
      placed in ovariectomized rats (OVX). METHODS: One screw-type titanium implant was
      placed bilaterally in the ovariectomized rats, and the animals assigned to one of
      the following groups: group 1 (n = 15): sham surgeries; group 2 (n = 15): OVX;
      group 3 (n = 14): OVX subcutaneously administered with calcitonin (CT) 4
      days/week (16 IU/kg); group 4 (n = 14): OVX administered daily with 17beta
      estradiol (20 microg/kg). After 60 days, the animals were sacrificed and
      undecalcified sections obtained. Blood samples were collected to measure serum
      levels of alkaline phosphatase and calcium at the time of sacrifice. Bone density
      was measured in a 500 microm wide mineralized zone lateral to the implant.
      RESULTS: Alkaline phosphatase levels in groups 2 and 3 (P > 0.05) were
      statistically higher than groups 1 and 4 (P < 0.05), and calcium serum levels
      were higher in group 2 than the other groups (P < 0.05). Regarding bone density,
      the data were grouped separately for cortical (zone A) and cancellous (zone B)
      bone. In zone A, intergroup analysis revealed no significant difference among
      groups (P > 0.05). However, in zone B, the animals that received estrogen
      administration (group 4) presented a higher bone density than groups 2 and 3 (P <
      0.05). CONCLUSION: It appears that estrogen therapy may prevent the negative
      influence of endogenous estrogen deficiency on bone density around titanium
      implants placed in ovariectomized rats.

PMID- 14682659
TI  - Cyclosporin A induces proliferation in human gingival fibroblasts via induction
      of transforming growth factor-beta1.
AB  - BACKGROUND: Cyclosporin A (CsA) is a widely used immunosuppressant that causes
      significant side effects including gingival overgrowth. The pathogenesis of this
      condition is not fully understood; however, recent studies show that CsA
      regulates the transcription of several cytokines including transforming growth
      factor-beta 1 (TGF-beta1). In this study, we evaluated the effects of CsA and TGF
      beta1 on human normal gingival (NG) fibroblast proliferation, and explored a
      possible autocrine stimulation of TGF-beta1 as a cellular regulator of
      proliferation induced by CsA in NG fibroblasts. METHODS: NG fibroblast cell lines
      were incubated with increasing concentrations of CsA or TGF-beta1 and the
      proliferation index determined by automatic cell counting, BrdU incorporation,
      PCNA expression, and mitotic potential. To determine the effect of TGF-beta1 on
      the proliferation rate of NG fibroblasts under CsA treatment, NG fibroblast
      cultures were simultaneously treated with CsA and antisense oligonucleotides
      against the translation-start site of the TGF-beta1 mRNA. RESULTS: Treatment of
      NG fibroblasts with CsA or TGF-beta1 significantly stimulated the cell
      proliferation in a dose-dependent manner. Furthermore, neutralization of TGF
      beta1 production in CsA-treated NG fibroblasts inhibited CsA's effect on NG
      fibroblast proliferation, demonstrating an autocrine stimulatory effect of TGF
      beta1 in CsA-treated NG fibroblast proliferation. CONCLUSION: The results
      presented here suggest that CsA stimulatory induction of NG fibroblast
      proliferation is mediated via TGF-beta1 in an autocrine fashion.

PMID- 14682660
TI  - Prevalence of human herpesviruses in patients with aggressive periodontitis.
AB  - BACKGROUND: Recent studies have demonstrated that various human viruses,
      especially cytomegalovirus (HCMV) and Epstein-Barr virus type-1 (EBV-1), seem to
      play a part in the pathogenesis of human periodontitis. The aim of this
      investigation was to evaluate the subgingival presence of HCMV and EBV in
      patients with aggressive periodontitis (AgP) and healthy subjects and to examine
      the effect of treatment on the incidence of these viruses 3 months following
      surgery. METHODS: A polymerase chain reaction (PCR) method determined the
      presence of HCMV and EBV-1. Subgingival plaque samples from 17 consecutive AgP
      patients and 16 healthy controls were collected. The following indices were
      measured: plaque index (PI), gingival index (GI), probing depths (PD), and
      clinical attachment loss (CAL). Clinical parameters were assessed pretherapy and
      at 3 months following surgical and antimicrobial therapy. RESULTS: HCMV was
      detected in 64.7% of AgP patients but not detected in healthy subjects (P <
      0.001) and EBV-1 in 70.6% of AgP patients and 6.3% of the healthy controls (P <
      0.001). HCMV and EBV-1 coinfection was detected in 41.7% of AgP patients. A
      statistically significant decrease was found in all clinical parameters 3 months
      after treatment. There was a statistically significant decrease in HCMV and EBV-1
      following therapy (P < 0.001; no HCMV; 1 patient with EBV-1). CONCLUSIONS: These
      findings indicate that subgingival presence of EBV-1 HCMV is strongly associated
      with aggressive periodontitis, and coinfection with HCMV and EBV-1 appears to be
      particularly deleterious to periodontal health.

PMID- 14682661
TI  - In vivo effectiveness of a glycerol-compounded demineralized freeze-dried bone
      xenograft in the rat calvarium.
AB  - BACKGROUND: Demineralized freeze-dried bone (DFDB) is commonly hydrated with
      sterile water into a paste-like consistency for improved clinical handling or
      reconstituted with biodegradable barriers, such as glycerol, to promote handling
      and wound stability following human periodontal surgery. The purpose of this
      study was to evaluate the in vivo effects of glycerol-compounded human DFDB on
      bone formation in the rat calvarial critical-sized defect (CSD) model. METHODS:
      Forty-eight adult male Harland Sprague-Dawley rats were assigned to one of four
      treatment groups: glycerol, DFDB, DFDB plus glycerol, or a non-grafted control,
      and placed into 8 mm calvarial CSDs. DFDB (particle size 0.106 to 0.5 mm),
      glycerol, and their combination were from identical sources. Calvaria were
      harvested at 8 weeks postsurgery and evaluated histomorphometrically. RESULTS: A
      statistically significant increased percentage of total bone fill was detected in
      the glycerol plus DFDB group and DFDB group as compared to glycerol group or the
      control. However, no significant difference was noted between the DFDB plus
      glycerol group and the DFDB group. CONCLUSION: The addition of glycerol to DFDB
      results in comparable osseous regeneration in the rat calvarium defect model
      versus DFDB alone; however, based upon clinical judgment, handling
      characteristics of DFDB were greatly improved.

PMID- 14682662
TI  - Effects of chlorhexidine, minocycline, and metronidazole on Porphyromonas
      gingivalis strain 381 in biofilms.
AB  - BACKGROUND: Porphyromonas gingivalis is found in subgingival biofilm and is
      associated with periodontal disease. Bacteria in biofilms are able to resist
      higher antimicrobial concentrations than in suspension. Little is known about the
      susceptibility of P. gingivalis in biofilms to antimicrobial agents. The effects
      of chlorhexidine gluconate, minocycline hydrochloride, and metronidazole on P.
      gingivalis biofilms were examined in vitro. METHODS: P. gingivalis strain 381
      biofilms were prepared on 32 hydroxyapatite disks. At 0, 24, 72, and 144 hours
      after perfusion of the three antimicrobial agents, two disks from each device
      were used to assess the antimicrobial effects by adenosine triphosphate (ATP)
      bioluminescence, and for morphological investigation by scanning electron
      microscopy (SEM). RESULTS: Close relationships were found between the results of
      the ATP analyses and the SEM observations in all groups examined. A significant
      decrease (P < 0.001) in ATP content was found between the chlorhexidine-treated
      and control groups. The extracellular matrix structure and P. gingivalis cells
      were altered in the presence of chlorhexidine. Minocycline hydrochloride also
      caused a decrease (P < 0.05) in the ATP content and morphological change on P.
      gingivalis biofilms. Metronidazole showed no significant efficacy against P.
      gingivalis biofilms. CONCLUSION: Chlorhexidine gluconate was effective at
      reducing the viability of P. gingivalis 381 cells in biofilms, while minocycline
      hydrochloride and metronidazole exhibited weaker effects.

PMID- 14682663
TI  - Attachment of periodontal ligament cells to chlorhexidine-loaded guided tissue
      regeneration membranes.
AB  - BACKGROUND: Early exposure of a guided tissue regeneration (GTR) membrane in the
      oral cavity results in bacterial contamination, which may lead to failure or
      incomplete regeneration. Incorporation of antimicrobial agents in GTR membranes
      may be valuable to control membrane-associated infection during GTR therapy. The
      purpose of this study was to evaluate whether the incorporation of chlorhexidine
      into various GTR membranes improves the attachment of periodontal ligament cells
      in the presence of Actinobacillus actinomycetemcomitans. METHODS: The possible
      effects of chlorhexidine on the viability of primary human periodontal ligament
      (PDL) cells were determined using 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT), which measures cellular metabolic activity. An
      expanded polytetrafluoroethylene (ePTFE) membrane, glycolide fiber membrane, and
      collagen membrane were loaded with chlorhexidine and characterized. Attachment of
      PDL cells to the chlorhexidine-loaded membranes with or without A.
      actinomycetemcomitans was examined using scanning electron microscopy (SEM)
      analysis. RESULTS: Relative cellular viability of PDL cells was reduced to
      approximately 50% when 15 microg/ml (0.0015%) of chlorhexidine was used.
      Chlorhexidine released from the coated GTR membranes inhibited the growth of A.
      actinomycetemcomitans. At the concentration used in this study, chlorhexidine
      incorporated into the GTR membranes did not interfere with the attachment of PDL
      cells. The inhibitory effects of A. actinomycetemcomitans on cellular attachment
      were reduced using chlorhexidine-loaded membranes, including ePTFE, glycolide
      fiber, and collagen membranes. CONCLUSIONS: These results suggest that
      incorporation of chlorhexidine into GTR membranes is beneficial in reducing
      bacterial effects on cellular attachment. The future application of chlorhexidine
      loaded membranes during GTR therapy may be of value.

PMID- 14682664
TI  - Gingival depigmentation by erbium:YAG laser: clinical observations and patient
      responses.
AB  - BACKGROUND: Melanin, carotene and hemoglobin are the most common natural pigments
      contributing to the normal color of the gums. Although physiologic and ethnic
      melanin pigmentation is not a medical problem, complaints about "black gums" are
      common. Gingival depigmentation has been carried out using non-surgical and
      surgical procedures. Recently, laser ablation has been recognized as a most
      effective, pleasant and reliable technique. METHODS: The study included 10
      patients who requested cosmetic therapy for melanin pigmented gums. Treatment was
      carried out using an erbium:YAG laser. The laser beam was set at 500 mJ/10
      pulses/second. The beam was defocused to produce a 3 mm diameter circle, thus
      reducing the beam penetration to 2 to 4 microm/pulse while increasing the treated
      surface. The "brush" technique was applied until the gingival surface appeared
      clinically free of pigmentation. Patients were observed for 6 months. Each
      patient filled out a personal evaluation questionnaire for clinical analysis.
      RESULTS: Between 500 to 1,100 pulses/cm2 were recorded and a total of 800 to
      2,200 pulses were required per patient, depending on the epithelium thickness and
      pigmentation. Treatment required only topical anesthesia. Healing was uneventful
      and required no supportive therapy. None of the patients experienced severe pain
      during or post-operatively. Mild pain or itching was common during the first
      week. Treatment was reported as generally pleasant. Follow-up during the 6 months
      showed no recurrences. CONCLUSIONS: Depigmentation of gingival melanin
      pigmentation by erbium:YAG laser radiation in a defocused mode was a safe and
      effective procedure. The esthetic results were pleasing and healing was
      uneventful. Since the erbium:YAG laser is available in the dental office, it
      seems to be the laser of choice for this procedure.

PMID- 14682665
TI  - Oral Kaposi sarcoma associated with severe alveolar bone loss: case report and
      review of the literature.
AB  - BACKGROUND: In AIDS patients who present with an oral neoplasm, Kaposi sarcoma is
      the tumor most frequently encountered, comprising 50% to 80% of all tumor
      occurrences. However, oral Kaposi sarcoma associated with erosion of underlying
      bone is a relatively rare finding. This report and review of the literature
      documents a case of AIDS-related oral Kaposi sarcoma exhibiting severe bilateral
      erosion of the maxillary alveolar ridges. METHODS: An HIV-seropositive male with
      extensive maxillary Kaposi sarcoma and associated bilateral alveolar bone erosion
      presented for dental evaluation subsequent to radiation therapy. Clinical and
      radiographic examinations were performed. Medical and dental histories were
      procured and supplemented with consultations from the patient's primary physician
      and radiation oncologist. Maxillary edentulation with surgical revision for
      primary closure was the treatment of choice for management of the dentoalveolar
      pathology. A maxillary immediate treatment denture was designed to obturate
      anticipated antral communications with the maxillary sinus. RESULTS: Surgical and
      prosthetic treatments were completed, but complicated by an oral-antral
      perforation that subsequently healed without complication. Soft tissue biopsies
      obtained during surgery revealed no evidence of residual Kaposi sarcoma.
      CONCLUSIONS: Although AIDS-related oral Kaposi sarcoma is a relatively common
      finding, erosion of subjacent alveolar bone is uncommon. Treatment of the tumor
      with subsequent dental reconstruction can be complicated by the severe lack of
      bone, surgical perforation of the maxillary sinus, and lack of stable teeth to
      serve as abutments. Significant advances in understanding the pathogenesis of
      AIDS-related Kaposi sarcoma have occurred in the last decade. HHV-8 and various
      inflammatory cytokines have been implicated in the pathogenesis and are likely to
      become the primary targets for therapeutic intervention.

PMID- 14682666
TI  - Gingival/soft tissue abscess following subepithelial connective tissue graft for
      root coverage: report of three cases.
AB  - BACKGROUND: The subepithelial connective tissue graft (SCTG) is a predictable
      technique for root coverage. The small number of potential postoperative problems
      make SCTG the current treatment of choice for reversing gingival recession.
      METHODS: The purpose of this article is to report three cases of complications
      after the use of an SCTG where an abscess occurred following the initial healing
      phase. The surgical technique that was used and the treatment that was provided
      for the abscesses are reported, and the possible causes of these complications
      are discussed. RESULTS: The abscesses were treated conservatively, and no
      recurrence has been observed after treatment. CONCLUSIONS: Possible causes of the
      abscesses include "stitch abscess" or reaction to the suture material used for
      the submerged sutures, or a possible role of epithelium implanted during the
      procedure. The clinical outcome of the root coverage procedure was not affected.

PMID- 14682667
TI  - Augmentation of the posterior maxilla: a proposed hierarchy of treatment
      selection.
AB  - Literature is reviewed that discusses treatment results following Cauldwel Luc
      approach sinus augmentation therapy or osteotome sinus augmentation therapy, with
      and without simultaneous implant placement. A hierarchy of treatment selection
      for the augmentation of the posterior maxilla, based upon quantity and position
      of residual alveolar bone crestal to the floor of the sinus, is proposed.

PMID- 14682668
TI  - Consideration of systemic hormone status when treating patients with osteopenia.

PMID- 14682669
TI  - Re: The influence of gingival margin recession on loss of clinical attachment in
      alcohol-dependent patients without medical disorders. Khocht A, Janal M,
      Schleifer S, Keller S (2003;74:485-493).

PMID- 14682670
TI  - Position paper: periodontal diseases of children and adolescents.
AB  - Children and adolescents are subject to several periodontal diseases. Although
      there is a much lower prevalence of destructive periodontal diseases in children
      than in adults, children can develop severe forms of periodontitis. In some
      cases, this destructive disease is a manifestation of a known underlying systemic
      disease. In other young patients, the underlying cause for increased
      susceptibility and early onset of disease is unknown. These diseases are often
      familial, suggesting a genetic predisposition for aggressive disease. Current
      modalities for managing periodontal diseases of children and adolescents may
      include antibiotic therapy in combination with non-surgical and/or surgical
      therapy. Since early diagnosis ensures the greatest chance for successful
      treatment, it is important that children receive a periodontal examination as
      part of their routine dental visits.

PMID- 14682671
TI  - A structure-technology contingency analysis of caregiving in nursing facilities.
AB  - The purpose of this paper is to describe how the work associated with
      psychosocial and physical caregiving is structured within nursing facilities.
      Arguing from a contingency perspective, our central hypothesis is that because
      the technology underlying physical care is less variable and more interpretable
      and the process-outcome relationships underlying care processes are better
      understood than for psychosocial care, work in the physical care domain will be
      comparatively more mechanistically structured even though work in both domains is
      performed by the same paraprofessional nurse aide staff. Data for this analysis
      derive from a survey of unit charge nurses (n = 739) in 308 nursing homes in
      eight states undertaken as part of a large NIA-funded study of the relationship
      between nursing home organization and resident outcomes. With the exception of
      centralization, contingency theory correctly predicts how the work associated
      with physical and psychosocial care is differentiated.

PMID- 14682672
TI  - The effects of relative resource configuration, organizational legitimacy, and
      integration on divestiture decisions among health systems.
AB  - This study examines the determinants of divestiture in health systems. Financial
      performance is a common indicator of a hospital's value. However, health systems
      may consider other factors that influence a hospital's value to the system. To
      enhance our understanding of hospital divestiture, we identify factors that
      enhance a hospital's value to the system and thus its likelihood of being
      retained. Our findings support previous studies that financial performance
      influences divestiture decisions. At the same time, our results identify three
      other factors influencing divestiture decisions: relative resource configuration,
      legitimacy, and integration.

PMID- 14682673
TI  - Agenda Setting for Health Care Management Research: report of a conference.

PMID- 14682675
TI  - Generating management research on improving quality.
AB  - This article identifies areas of management research that should be pursued to
      develop a better understanding of barriers and facilitators to improve quality in
      health care organizations. Five major structural barriers to improvement of
      quality are discussed. Research priorities are presented with suggestions on how
      to encourage more meaningful research that will accelerate quality improvement in
      health care.

PMID- 14682674
TI  - Management matters: strengthening the research base to help improve performance
      of safety net providers.
AB  - It is becoming increasingly apparent that some disparities in health outcomes for
      vulnerable populations relate to performance of providers. Based on analysis of
      Medicaid claims records, large differences in performance among primary care
      providers are documented for New York City patients, suggesting the need for
      better evidence in making management decisions.

PMID- 14682676
TI  - The case for the use of evidence-based management research for the control of
      hospital costs.
AB  - This article explores the current state of the creation and use of evidence by
      managers for cost containment in hospitals. We assert that hospitals do not know
      enough about what things cost, and until they get evidence on costs, it is not
      likely that much can be done to narrow the chasm between common practice and best
      practice. Part of the problem is that managers do not seek out available evidence
      that exists, and part of the problem is a lack of sufficient research efforts to
      generate evidence for managers to use. The article strives to help direct future
      efforts by researchers and managers in the area of evidence-based cost
      containment research by presenting a framework for priorities that managers and
      researchers can use to increase the amount of research done to generate evidence
      and to increase the use of evidence by health care managers.

PMID- 14682677
TI  - Improving the generation, dissemination, and use of management research.

PMID- 14682678
TI  - Unusual reactions of the model carcinogen N-acetoxy-N-acetyl-2-amino-alpha
      carboline.
AB  - The aqueous solution reactions of the title compound, 1, were examined for
      comparison to those previously reported for another model carcinogen N
      pivaloyloxy-2-amino-alpha-carboline, 2. Both of these are models for the ultimate
      carcinogenic metabolites of 2-amino-alpha-carboline (AalphaC), a food-derived
      heterocyclic amine mutagen and carcinogen. The present study was undertaken to
      determine the effect of the N-acetyl group on the chemistry of such compounds.
      The N-acetyl group slows down N-O bond cleavage by a factor of (5.5 x 10(3))
      fold. This allows other reactions not observed in 2, or in other model
      carcinogens, to be observed. Among these are acyl-transfer reactions to the
      aqueous solvent, both uncatalyzed and catalyzed by N3-. In addition, the
      conjugate acid of 1, 1H+, is subject to a spontaneous decomposition not
      previously observed in other esters of heterocyclic hydroxylamines or hydroxamic
      acids. This reaction yields the hydroxylamine, 5, and does so without the
      intermediacy of the hydroxamic acid, 3, and with 18O exchange from the solvent
      into the hydroxylamine O. This unique reaction may be caused by an intramolecular
      proton donation by the pyridyl N-H to the amide carboxyl that catalyzes an
      intramolecular nucleophilic attack by the carboxyl O of 1H+. A nitrenium ion
      pathway can still be detected for 1, but, unlike 2 and related esters, this
      reaction is in competition with other processes throughout the pH range of the
      study.

PMID- 14682680
TI  - Anodic oxidation of methyl alpha-dimethylsilyldihydrocinnamate. A novel silicon
      gamma-aryl effect.
AB  - The anodic oxidation of methyl 3-phenyl-2-dimethylsilylpropionate occurs at a
      potential almost 1 V positive of that required to oxidize other alpha-silyl
      esters. Semiempirical and ab initio calculations on the model compound 1-phenyl-2
      trimethylsilylethane indicate that electron removal from these two compounds is
      highly stereoelectronically dependent. Both molecules exist almost exclusively in
      a conformation in which the phenyl group and silicon atom are anti and the side
      chain is perpendicular to the aromatic ring. This conformation has a higher
      energy HOMO orbital and lower computed ionization potential than the only other
      significantly populated conformation of 1-phenyl-2-trimethylsilylethane. Finally,
      the ab initio calculations show that in the cation radical of this model compound
      the ipso carbon of the aromatic ring and the side chain carbon bound to silicon
      draw significantly closer together than in the neutral species; an electrostatic
      potential map of the cation radical shows that the ipso carbon bears the highest
      degree of positive charge of any of the benzenoid carbons. We interpret these
      data, taken together, as an indication that this cation radical is stabilized by
      overlap of the rear lobe of the carbon-silicon bond with the p-orbital of the
      ipso carbon.

PMID- 14682679
TI  - 5-cyanoimino-4-oxomethylene-4,5-dihydroimidazole and nitrosative guanine
      deamination. A theoretical study of geometries, electronic structures, and N
      protonation.
AB  - The 5-cyanoimino-4-oxomethylene-4,5-dihydroimidazole 1 (R = H), its N1
      derivatives 2 (R = Me) and 3 (R = MOM) and their cyano-N (4, 6, 8) and imino-N
      protonated (5, 7, 9) derivatives were studied with RHF, B3LYP, and MP2 theory.
      Solvation effects were estimated with the isodensity polarized continuum model
      (IPCM) at the MP2 level using the dielectric constant of water. Carbodiimide 10,
      cyanamide 12, N-cyanomethyleneimine 13, and its protonated derivatives 14 and 15
      were considered for comparison as well. Adequate theoretical treatment requires
      the inclusion of dispersion because of the presence of intramolecular van der
      Waals, charge-dipole, and dipole-dipole (including H-bonding) interactions. All
      conformers were considered for the MOM-substituted systems, and direct
      consequences on the preferred site of protonation were found. The vicinal push
      (oxomethylene)-pull (cyanoimino) pattern of the 5-cyanoimino-4-oxomethylene-4,5
      dihydroimidazoles results in the electronic structure of aromatic imidazoles with
      4-acylium and 5-cyanoamido groups. The gas-phase proton affinities of 1-3 are
      over 30 kcal/mol higher than that for N-cyanomethyleneimine 13, and this result
      provides compelling evidence in support of the zwitterionic character of 1-3.
      Protonation enhances the push-pull interaction; the OC charge is increased from
      about one-half in 1-3 to about two-thirds in the protonated systems. In the gas
      phase, cyano-N protonation is generally preferred but imino-N protonation can
      compete if the R-group contains a suitable heteroatom (hydrogen-bond acceptor,
      Lewis base). In polar solution, however, imino-N protonation is generally
      preferred. Solvation has a marked consequence on the propensity for protonation.
      Whereas protonation is fast and exergonic in the gas phase, it is endergonic in
      the polar condensed phase. It is an immediate consequence of this result that the
      direct observation of the cations 8 and 9 should be possible in the gas phase
      only.

PMID- 14682682
TI  - Study on the heteroatom influence in pyridine-based nitronyl nitroxide biradicals
      with phenylethynyl spacers on the molecular ground state.
AB  - Novel pyridine-based nitronyl nitroxide (NIT) biradicals, 3,5-bis[4-(1-oxyl-3-oxo
      4,4,5,5-tetramethylimidazolin-2-yl)phenylethynyl)]pyridine (1) and 2,6-bis[4-(1
      oxyl-3-oxo-4,4,5,5-tetramethylimidazolin-2-yl)phenylethynyl)]pyridine (2), and
      monoradicals, 4-(5-bromopyridine-3-ylethynyl)-1-(1-oxyl-3-oxo-4,4,5,5
      tetramethylimidazolin-2-yl)benzene (3), 4-trimethylsilylethynyl-1-(1-oxyl-3-oxo
      4,4,5,5-tetramethylimidazolin-2-yl)benzene (4), and 4-trimethylsilylethynyl-1-(1
      oxyl-3-oxo-4,4,5,5-tetramethylimidazolin-2-yl)pyridine (5), were synthesized and
      investigated by ESR and UV-vis spectroscopy. The solution EPR measurements of the
      biradicals gave well-resolved, nine-line spectra with exact half line spacing as
      compared to monoradicals (giso = 2.0067) with isotropic line spacing /aN/= 7.36
      G. This indicates strong, intramolecular exchange coupling (J >> 7 x 10(-4) cm(
      1); J/aN >> 1) of the biradicals with in the limit of EPR. The temperature
      dependence on the Deltams = +/-2 signal intensity of biradicals follow Curie
      behavior down to 4 K ascertaining the triplet ground state or its near-degeneracy
      with the singlet state. UV-vis studies of 1-5 show characteristic differences in
      the extinctions of n-pi transitions around 600 nm. Both biradicals 1 and 2 were
      crystallized in monoclinic space groups C2/c and P2(1)/a with the intraradical
      distances 1.54 and 1.47 nm, respectively. Computational studies of the biradicals
      1, 2, and 1,3-bis[4-(1-oxyl-3-oxo-4,4,5,5-tetramethylimidazolin-2
      yl)phenylethynyl)]benzene (T) were performed by the AM1/CAS(8,8) method to
      calculate the singlet-triplet (DeltaEST) energy difference and the spin density
      distribution. Results show that the position of the pyridyl nitrogen in 1 and 2
      in comparison with T does not alter the triplet ground-state spin multiplicities
      supporting the obtained experimental results.

PMID- 14682681
TI  - Synthesis of erythro-alpha-amino beta-hydroxy carboxylic acid esters by
      diastereoselective photocycloaddition of 5-methoxyoxazoles with aldehydes.
AB  - A new photoaldol route to alpha-amino-beta-hydroxy carboxylic acid esters is
      initiated by the photocycloaddition of aromatic or aliphatic aldehydes to 5
      methoxyoxazoles. The 4-unsubstituted 5-methyloxazole 1 gave the cycloadducts 8a-f
      in high yields and excellent exo-diastereoselectivities. Hydrolysis of 8a-f gives
      the N-acetyl alpha-amino-beta-hydroxy esters 9a-f, which could be subsequently
      converted into the corresponding Z-didehydro alpha-amino acids 10a-f. Quartenary
      alpha-amino-beta-hydroxy esters 12, 14, 16, 18, and 20, which are stable against
      dehydration, were obtained from the 4-alkylated 5-methoxyoxazoles 2-6, in most
      cases highly erythro-selective due to the high degree of stereocontrol (exo) at
      the photocycloaddition (to give 11, 13, 15, 17, and 19) level. The relative
      configurations of the N-acetyl alpha-amino-beta-hydroxy esters were determined by
      NMR spectroscopy and comparison with chiral pool-derived compounds as well as by
      X-ray structure determination of the ester 23, formed by hydrolysis of the
      cycloadduct 22, derived from photocycloaddition of propionaldehyde to the
      isoleucine-derived oxazole 21.

PMID- 14682683
TI  - Phosphonyl, phosphonothioyl, phosphonodithioyl, and phosphonotrithioyl radicals:
      generation and study of their addition onto alkenes.
AB  - The treatment of benzyl dialkyl phosphites and dithiophosphites with
      benzeneselanyl chloride generates an Arbuzov-type transformation leading to the
      dialkyl selenophosphates 19a and 19b and to selenophosphorodithioates 21a and
      21b. Interaction of these substrates with Lawesson's reagent yields the
      corresponding selenophosphorothioates 20a and 20b and the
      selenophosphorotrithioates 22a and 22b. When treated with a radical initiator in
      the presence of a hydrogen donor and an alkene, all eight phosphorus(V)
      precursors undergo homolytic cleavage of the P-Se bond to generate the
      phosphonyl, phosphonothioyl, phosphonodithioyl, or phosphonotrithioyl radicals.
      Most of these are shown to add onto electron-rich and electron-poor alkenes to
      deliver the expected adducts in fair to excellent yields. Cyclic precursor 19b
      displays peculiar behavior and, under the reaction conditions, produces only the
      corresponding cyclic phosphite. Application of this radical chain process is
      carried out on furanosyl 3-exo-methylene derivative 37 to diastereoselectively
      furnish five new 3-phosphonomethyl-, 3-phosphonothiomethyl-, and 3
      phosphonodithiomethyl-3-deoxofuranoses 38a-c and 38f,g. The possibility of
      conducting tandem processes is also discussed through experiments involving (1R)
      (+)-alpha-pinene (39) and diallylamine 41.

PMID- 14682684
TI  - Synthesis of cyclopropene analogues of ceramide and their effect on
      dihydroceramide desaturase.
AB  - The synthesis of several analogues of the N-[(1R,2S)-2-hydroxy-1-hydroxymethyl-2
      (2-tridecyl-1-cyclopropenyl)ethyl]octanamide (GT11), the first reported inhibitor
      of dihydroceramide desaturase, as well as their effects on this enzyme, are
      described. Modifications of the parent structure include variations on the
      cyclopropene ring, the N-acyl chain length, the configuration of the
      stereocenters, and the hydroxyl group at C1. The key intermediates for the
      synthesis are the products resulting from the addition of suitable organolithium
      compounds to either Garner's aldehyde or its enantiomer. The final products are
      obtained by TMSTf-induced cleavage of the protecting groups and N-acylation, both
      under specific conditions. An alternative method for N-Boc deprotection is also
      reported that allows us to obtain the cyclopropene analogue of sphingosine 12a,
      which can be transformed into GT11 upon acylation. The procedure consists of the
      conversion of the Garner aldehyde addition products into the bicyclic
      dihydrooxazolo[3,4,0]oxazol-3-ones 19 by transesterification in basic medium of
      the tert-butyl group with the hydroxyl function at C3. Mild cleavage of the N,O
      isopropylidene cyclic acetal present in 19 affords the oxazolidin-2-one 20, which
      gives 12a upon saponification. Furthermore, compound 20 is also the key
      intermediate in the synthesis of the terminal deoxy, methoxy, and fluoro
      derivatives 9, 10, and 11, respectively. Determination of dihydroceramide
      desaturase activity in vitro showed that GT11 was a competitive inhibitor (Ki = 6
      microM) and that its analogues with N-hexanoyl (6) and N-decanoyl (7) moieties
      inhibited the enzyme with similar potencies (IC50 = 13 and 31 microM,
      respectively). No decrease in dihydroceramide desaturase activity was observed
      with any of the other compounds tested.

PMID- 14682685
TI  - Kinetics of the grignard reaction with silanes in diethyl ether and ether-toluene
      mixtures.
AB  - Kinetics of the reactions of butylmagnesium chloride and phenylmagnesium bromide
      with tetraethoxysilane and methyltrichlorosilane was investigated in diethyl
      ether and diethyl ether-toluene mixtures. Replacement of ether by toluene
      significantly accelerates the reaction with alkoxysilanes, while no effect was
      found for the reaction with chlorosilanes. We established that the reaction with
      alkoxysilanes consists of replacement of a donor molecule at the magnesium center
      by the silane followed by subsequent rearrangement of the complex to products
      through a four-center transition state. Chlorosilanes react differently without
      solvent molecule replacement but also via a four-center transition state. Large
      negative activation entropies are consistent with formation of cyclic transition
      states. Small activation enthalpy values together with remarkable exothermicity
      point to early transition states of the reactions.

PMID- 14682686
TI  - A new and efficient synthesis of pyrrolo[2,3-d]pyrimidine anticancer agents:
      Alimta (LY231514, MTA), homo-Alimta, TNP-351, and some aryl 5-substituted
      pyrrolo[2,3-d]pyrimidines.
AB  - Alimta, as well as homo-Alimta, a nonbridged analogue of Alimta, and TNP-351 have
      been prepared by a new method that involves Michael addition of the appropriate 1
      nitroalkene with 2,6-diamino-3H-pyrimidin-4-one or 2,4,6-triaminopyrimidine,
      followed by a Nef reaction of the resulting primary nitro Michael adduct.
      Spontaneous intramolecular cyclization of the resulting aldehyde with the
      pyrimidine 6-amino group yields the corresponding pyrrolo[2,3-d]pyrimidine. A
      series of previously unknown 5-arylpyrrolo[2,3-d]pyrimidines was prepared by the
      same methodology from the above pyrimidines and nitrostyrenes. It has been found
      that the intermediate primary nitro Michael adduct can be prepared in a single
      step by sonication of a mixture of an arylaldehyde, nitromethane, and the 6
      aminopyrimidine in acetic acid containing ammonium acetate.

PMID- 14682687
TI  - Stereoselective synthesis of 1,2-disubstituted beta-amino alcohols by
      nucleophilic addition to N-tert-butanesulfinyl alpha-alkoxyaldimines.
AB  - N-tert-Butanesulfinyl alpha-alkoxyaldimines are readily prepared from protected
      (S)-lactals without epimerization at the alpha-stereocenter. Addition of ethyl
      and phenyl Grignard reagents, as well as the titanium enolate of methyl acetate,
      to the N-tert-butanesulfinyl aldimines provides 1,2-disubstituted beta-amino
      alcohols in good yields (73-98%) and with high diastereoselectivities. Either syn
      or anti-amino alcohol products can be obtained by the appropriate choice of
      alcohol protecting groups and/or reaction conditions. Finally, deprotection of
      the addition products provides straightforward access to either syn- or anti-1,2
      amino alcohols.

PMID- 14682688
TI  - Investigation of Lewis acid-catalyzed asymmetric aza-Diels-Alder reactions of 2H
      azirines.
AB  - Asymmetric Diels-Alder reactions with 2H-azirines as dienophiles have been
      studied. Diastereoselective reactions with an enantiopure azirine 1b, bearing a
      chiral auxiliary, gave substituted bi- and tricyclic tetrahydropyridines in high
      yield and stereoselectivity, under the influence of a Lewis acid. The novel
      enantioselective [4+2] cycloaddition reaction of 3-benzyl-2H-azirine carboxylate
      with cyclopentadiene was investigated with various chiral Lewis acid complexes
      and provided the corresponding tetrahydropyridines in moderate to low yield and
      enantioselectivity.

PMID- 14682689
TI  - Unexpected migration and oxidative cyclization of substituted 2-acetophenone
      triflates under basic conditions: synthetic and mechanistic insights.
AB  - Oxidative ring closure of alkyl-substituted 2-hydroxyacetophenone
      trifluoromethanesulfonate esters (triflates) occurs upon exposure to base in
      anaerobic DMF at 20-90 degrees C. Alkyl substitution is required for ring
      closure. A migrated enol triflate product forms at lower temperature in high
      yield via migration of the trifluoromethanesulfonate in the unsubstituted and
      monoalkyl-substituted cases. The alkyl-substituted enol triflates also enter into
      the benzofuran-3-one ring-forming process under thermal cyclization conditions.
      Potential mechanistic pathways are evaluated.

PMID- 14682690
TI  - A new route to 2'-O-alkyl-2-thiouridine derivatives via 4-O-protection of the
      uracil base and hybridization properties of oligonucleotides incorporating these
      modified nucleoside derivatives.
AB  - Oligonucleotides containing 2-thiouridine (s2U) in place of uridine form stable
      RNA duplexes with complementary RNAs. Particularly, this modified nucleoside has
      proved to recognize highly selectively adenosine, the genuine partner, without
      formation of a mismatched base pair with the guanosine counterpart. In this
      paper, we describe new methods for the synthesis of 2-thiouridine and various 2'
      O-alkyl-2-thiouridine derivatives. Oligoribonucleotides having these modified
      nucleoside derivatives were synthesized, and their hybridization and structural
      properties were studied in detail by the 1H NMR analysis of these modified
      nucleosides and Tm experiments of RNA duplexes with their complementary RNA
      strands.

PMID- 14682691
TI  - Pyranophane transannular diels-alder approach to (+)-chatancin: a biomimetic
      asymmetric total synthesis.
AB  - An asymmetric total synthesis of (+)-chatancin was achieved via a transannular
      Diels-Alder (TADA) reaction of an in situ generated macrocyclic pyranophane
      pseudobase. The presented route constitutes the second of two proposed
      biosynthetic pathways that involves a TADA reaction. It links this diterpene
      biogenetically to the cembranoids. A set of TADA selection rules that rationalize
      the formation of (+)-chatancin from a dynamic equilibrium of four 2-hydroxy-2H
      pyrane bicycles and their 16 potential TADA transition states are also outlined.
      Beyond the TADA reaction, highlights of the synthetic work include the assembly
      of a chiral acyclic macrocyclization substrate from (S)-citronellol and an
      efficient macrocyclization via a beta-ketosulfoxyde/enone Michael addition.

PMID- 14682692
TI  - Acid-base equilibria in nonpolar media. 4. Extension of the self-consistent
      basicity scale in THF medium. Gas-phase basicities of phosphazenes.
AB  - Eleven new phenyl-substituted phosphazenes (P1-, P3-, and P4-bases) have been
      synthesized by the Staudinger or the Kirsanov reactions. The UV-vis
      spectrophotometric titration method was used to establish the relative basicity
      of them, and to extend the ion-pair basicity scale for THF medium. These
      measurements together with our previous work give a continuous basicity scale in
      THF ranging from 2.6 (2-MeO-pyridine) to 26.6 (2-Cl-C6H4P4(pyrr) phosphazene) in
      pKalpha units: that is for 24 orders of magnitude and containing 58 compounds
      (pyridines, anilines, amines, guanidines, amidines, phosphazenes). Ion-pair
      formation was taken into account by using the Fuoss equation. DeltapKip values of
      some phosphazene indicators estimated earlier by the 13C NMR method were revised.
      For some of the phosphazenes gas-phase basicities were measured.

PMID- 14682693
TI  - Synthesis of the c14-c25 subunit of bafilomycin A1.
AB  - The enantioselective synthesis of the C14-C25 subunit of bafilomycin A1 was
      realized in a convergent route. The sequence involves two dynamic kinetic
      resolution steps of 2-alkyl 1,3-diketones that use optically active ruthenium
      complexes, an anti-selective reduction of a beta-hydroxyketone to control the C23
      stereogenic center, and an aldol-type reaction under Evans' conditions, which
      sets the C17 and C18 stereogenic centers.

PMID- 14682694
TI  - Thermolytic carbonates for potential 5'-hydroxyl protection of
      deoxyribonucleosides.
AB  - Thermolytic groups structurally related to well-studied heat-sensitive
      phosphate/thiophosphate protecting groups have been evaluated for 5'-hydroxyl
      protection of deoxyribonucleosides as carbonates and for potential use in solid
      phase oligonucleotide synthesis. The spatial arrangement of selected functional
      groups forming an asymmetric nucleosidic 5'-O-carbonic acid ester has been
      designed to enable heat-induced cyclodecarbonation reactions, which would result
      in the release of carbon dioxide and the generation of a nucleosidic 5'-hydroxyl
      group. The nucleosidic 5'-O-carbonates 3-8, 10-15, and 19-21 were prepared and
      were isolated in yields ranging from 45 to 83%. Thermolytic deprotection of these
      carbonates is preferably performed in aqueous organic solvent at 90 degrees C
      under near neutral conditions. The rates of carbonate deprotection are dependent
      on the nucleophilicity of the functional group involved in the postulated
      cyclodecarbonation reaction and on solvent polarity. Deprotection kinetics
      increase according to the following order: 4 < 5 < 10 < 6 < 12 < 7 < 13 < 8 < 14
      congruent with 19-21 and CCl4 < dioxane < MeCN < t-BuOH < MeCN:phosphate buffer
      (3:1 v/v, pH 7.0) < EtOH:phosphate buffer (1:1 v/v, pH 7.0). Complete thermolytic
      deprotection of carbonates 7, 8, 13, and 14 is achieved within 20 min to 2 h
      under optimal conditions in phosphate buffer-MeCN. The 2-(2-pyridyl)amino-1
      phenylethyl and 2-[N-methyl-N-(2-pyridyl)]aminoethyl groups are particularly
      promising for 5'-hydroxyl protection of deoxyribonucleosides as thermolytic
      carbonates.

PMID- 14682695
TI  - Formal asymmetric 1,3-dipolar cycloaddition of azomethine ylides to (S)-2-p
      tolylsulfinyl-2-cyclopentenone.
AB  - Azomethine ylides, derived from iminoesters 1 and DBU in the presence of silver
      salts, react with (S)-2-p-tolylsulfinyl-2-cyclopentenone 2 in a completely regio-
      and endoselective manner but with a low facial selectivity, affording a mixture
      of two cycloadducts 3 and 4. When the ylides were prepared with LHMDS, only one
      diastereoisomer 3 was obtained in an almost quantitative yield. A nucleophilic
      addition/ring closure process easily accounts for the stereochemical results.
      Compounds 3 were transformed into optically pure 4
      oxocyclopenta[c]dihydropyrroles and tetrahydropyrroles by elimination of the
      sulfinyl group.

PMID- 14682696
TI  - Total syntheses of variolin B and deoxyvariolin B.
AB  - Two alternative synthetic routes have been developed for the preparation of
      variolin B and deoxyvariolin B. The strategy is based on the preparation of the
      core tricyclic ring common to all variolins, pyrido[3',2':4,5]pyrrolo[1,2
      c]pyrimidine, followed by a palladium-catalyzed cross-coupling reaction to give
      the tetracyclic system.

PMID- 14682697
TI  - Formal total synthesis of (+)-salicylihalamides A and B: a combined chiral pool
      and RCM strategy.
AB  - The formal total synthesis of the (+)-salicylihalamides A and B is detailed,
      utilizing a chiral pool approach to generate the three stereogenic centers and a
      ring-closing metathesis (RCM) for the formation of the macrocyclic ring
      structure. Starting from a known glucose-derived alcohol, the formal total
      synthesis was achieved in an efficient 13-step protocol in 26% overall yield. It
      was found that substitution at the remote phenolic group significantly influenced
      the ratio of the E- and Z-double bond products in the RCM step. The introduction
      of phenol protecting groups provided E-isomers preferentially and also enhanced
      the rates of the RCM reactions.

PMID- 14682698
TI  - Carbon-carbon bond formation reaction of ethereal oxonium ylides via metal
      enolate intermediates.
AB  - First, the carbon-carbon (C-C) bond-forming reaction of aldehydes with
      bicyclo[m.n.0]-1-oxonium ylides was studied as the ylide was transiently formed
      in the Rh(II)-catalyzed reaction of a nonenolizable diazoketone, namely, 2-(3
      diazo-1,1-dimethyl-2-oxopropyl)-2-methyldioxolane (1). The reaction of 1 with
      benzaldehyde in the presence of ClTi(Oi-Pr)3 gave the three-carbon, ring
      enlarged, and C-C-bonded product 2a (53%). Second, enolizable diazoketone 5
      bearing no methyl substituents at the alpha-position was studied under similar
      catalytic conditions, and the ring-enlarged and C-C-bonded products 19a and 20a
      were also formed (87%) when titanium compound ClTi(Oi-Pr)3 or Ti(Oi-Pr)4 was
      used. Similar reactions of diazoketones 27, 29, and 31 bearing a cyclic acetal
      ring and a longer tethering chain than 5 gave C-C-bonded products 28 (74%), 30
      (8%), and 32 and 33 (overall 48%), respectively, albeit 28 and 30 possessed a
      spiro bisacetal structure. Thus, the hitherto unclarified C-C bond formation of
      ethereal oxonium ylides with carbonyl electrophiles was realized with the use of
      an appropriate Lewis acid, for example, ClTi(Oi-Pr)3.

PMID- 14682700
TI  - Donor-sigma-acceptor molecules incorporating a nonadecyl-swallowtailed
      perylenediimide acceptor.
AB  - Donor-sigma-acceptor-lipid molecules were prepared by using
      perylenetetracarboxylic diimide as the acceptor, starting from
      perylenetetracarboxylic dianhydride. One imide nitrogen was attached to a
      "swallowtail" lipid (a long alkyl tail connected at midchain), which imparts
      enough solubility to make the system tractable and provides a lipophilic region
      suitable for promoting Langmuir-Blodgett monolayer formation. The other imide
      link was to a donor group (pyrene, ferrocene, tetramethylphenylenediamine,
      phenyl) through a short alkyl sigma bridge. Features of the 1H and 13C NMR
      spectra of swallowtailed perylenediimides are interpreted as resulting from
      restricted rotation about the imide C-N bond; the 13C NMR spectra and
      stereochemistry of these molecules are contrasted with the case of the related
      bis-(2,5-di-tert-butylphenyl)perylenetetracarboxylic diimide.

PMID- 14682699
TI  - Enantioselective Lewis acid-catalyzed Mukaiyama-Michael reactions of acyclic
      enones. Catalysis by allo-threonine-derived oxazaborolidinones.
AB  - allo-Threonine-derived O-aroyl-B-phenyl-N-tosyl-1,3,2-oxazaborolidin-5-ones 1g,n
      catalyze the asymmetric Mukaiyama-Michael reaction of acyclic enones with a
      trimethylsilyl ketene S,O-acetal in high enantioselectivity. A range of alkenyl
      methyl ketones is successfully employed as Michael acceptors affording ee values
      of 85-90% by using 10 mol % of the catalyst. The use of 2,6-diisopropylphenol and
      tert-butyl methyl ether as additives is found to be essential to achieve high
      enantioselectivity in these reactions. The effects of the additives are discussed
      in terms of the retardation of an Si(+)-catalyzed racemic pathway, which
      seriously deteriorates the enantioselectivity of asymmetric Mukaiyama-Michael
      reactions. A working model for asymmetric induction is proposed based on
      correlation between catalyst structures and enantioselectivities.

PMID- 14682701
TI  - Competitive intermolecular pericyclic reactions of free and complexed
      cyclopentyne.
AB  - Intermolecular competition for cyclopentyne by different alkenes supports the
      hypothesis that organolithium-promoted decomposition of precursors to
      cyclopentyne affords one or more lithium-ion-complexed species. Competition
      reactions with mixtures of 2,3-dihydropyran do not clearly differentiate between
      complexed and unencumbered (free) forms of cyclopentyne, but those involving
      spirodiene 2 and cyclohexene do. Remarkably, the cycloaddition reactions of free
      cyclopentyne are not diffusion-controlled despite its high reactivity.

PMID- 14682702
TI  - Synthesis and supramolecular properties of conformationally restricted and
      flexible phospholipids.
AB  - Short synthetic routes are described to produce structurally related
      phospholipids that are either conformationally restricted or flexible. The
      conformationally restricted structures have a cyclopropyl ring in the interfacial
      region of the phospholipid. The key synthetic step is a cyclopropanation reaction
      between 2(5H)-furanone and a stabilized chloroallylic phosphonate anion. The
      synthetic routes enable the incorporation of different polar headgroups as well
      as nonpolar tails at late stages in the sequence. The phosphoethanolamine
      derivatives 1b and 2b readily form encapsulating vesicles, however, dye leakage
      from vesicles composed of the restricted phospholipid 1b is significantly slower
      than from vesicles composed of flexible analogue 2b. Physicochemical analyses
      using 31P NMR, differential scanning calorimetry, fluorescence anisotropy, and
      Langmuir-Blodgett films suggest that the decreased permeability of membranes
      composed of conformationally restricted 1b is due to its ability to pack more
      closely in a bilayer assembly.

PMID- 14682703
TI  - Mechanistic studies of the biomimetic epoxy ester-orthoester and orthoester
      cyclic ether rearrangements.
AB  - The relative rates of acid-catalyzed rearrangements of epoxy esters to
      [3.2.1]bicyclic orthoesters, the subsequent rearrangements of these ortho esters
      to substituted tetrahydrofurans, and the rates of orthoester hydrolysis at pH
      4.75 were measured in NMR kinetics experiments. The ease of formation and
      stabilities of these orthoesters compared favorably with the OBO-type
      [2.2.2]bicyclic orthoesters typically used as protecting groups of carboxylic
      acids. Studies with 13C NMR-detected 18O-labeling show that epoxy ester
      rearrangement takes place preferentially via 6-exo cyclization, although the 7
      endo process competes when the distal center of the epoxide is disubstituted. The
      ortho ester-cyclic ether rearrangement was shown by 18O-labeling to occur
      exclusively via intermediacy of a five-membered dioxonium ion. The structures of
      the hydrolysis products also indicate the intermediacy of a dioxolanium ion
      during hydrolysis. The implications for a hypothetical biosynthesis of marine
      polyether toxins are discussed.

PMID- 14682704
TI  - Stereoselective synthesis of stannyl enones via palladium-catalyzed and free
      radical hydrostannation of alkynyl ketones with trineophyltin hydride.
AB  - A study on the addition of trineophyltin hydride (1) to alkynones under free
      radical (AIBN and Et3B) and palladium-catalyzed [(PPh3)2PdCl2] conditions is
      reported. The results obtained indicate that the addition of 1 to eight ynones
      catalyzed by bis(triphenylphosphine)palladium(II) chloride led in all cases to
      addition products in very high yields (80-96%). These additions take place with
      excellent regio- and stereochemistry, leading to the alpha adducts as major
      products in seven out of the eight cases studied. Also the E adducts, resulting
      from a syn attack, were the only (seven cases) or the predominant (one case)
      products. The radical hydrostannations initiated by AIBN of ynones 2-5 with 1 led
      to addition products in good yields (60-88%); with the more hindered ketones 6
      and 7-9 the yields obtained were lower. The radical additions initiated by
      triethylboron to ynones 2-6 follow a similar pattern but with lower yields; no
      addition products in the hydrostannation of ynones 7-9 were detected. The new
      acyl-substituted vinylstannanes, owing to their greater stability compared with
      that of their tributyl- and trimethylstannyl analogues, can be purified by column
      chromatography using neutral alumina (in all cases) or silica gel 60 (in most
      cases) as adsorbents. Full 1H, 13C, and 119Sn NMR data are given.

PMID- 14682705
TI  - Synthesis of 2-amino-4-pyrimidinones from resin-bound guanidines prepared using
      bis(allyloxycarbonyl)-protected triflylguanidine.
AB  - We have synthesized novel heterocyclic compounds from resin-bound guanidines. For
      this purpose, an amine immobilized on a solid support was acylated with protected
      amino acids. Following the deprotection, the liberated amines were guanidinylated
      utilizing a new member of the family of diurethane-protected triflyl guanidine
      reagents, N,N'-bis(allyloxycarbonyl)-N' '-triflylguanidine. The deprotected
      guanidines were subsequently regioselectively cyclized with beta-keto esters
      yielding novel compounds containing heterocyclic structures in high purities.

PMID- 14682706
TI  - Michael addition of amines and thiols to dehydroalanine amides: a remarkable rate
      acceleration in water.
AB  - In water, the rate of Michael addition of amines and thiols to dehydroalanine
      amides was greatly accelerated, leading to shorter reaction times and higher
      yields. The scope of the new conditions was tested with a range of amines,
      thiols, and dehydroalanine amides. The ease and efficiency of this method
      provides an attractive route to the synthesis of natural and unnatural amino acid
      derivatives.

PMID- 14682707
TI  - Reductive PET cycloreversion of oxetanes: singlet multiplicity, regioselectivity,
      and detection of olefin radical anion.
AB  - Cycloreversion of 2-(p-cyanophenyl)-4-methyl-3-phenyloxetane (1) is achieved
      using 1-methoxynaphthalene (2) as electron-transfer photosensitizer. The
      experimental results are consistent with the reaction taking place from the
      singlet excited state of the sensitizer. Ring splitting of the radical anion 1*-
      occurs with cleavage of O-C2 and C3-C4 bonds, leading to products (acetaldehyde
      and p-cyanostilbene) different from the reagents used in the Paterno-Buchi
      synthesis of 1. The olefin radical anion involved in the electron-transfer
      process has been detected by means of laser flash photolysis.

PMID- 14682708
TI  - Organometallic synthesis, molecular structure, and coloration of 2,7
      disubstituted 1,8-bis(dimethylamino)naphthalenes. How significant is the
      influence of "buttressing effect" on their basicity?
AB  - On treatment of 2,7-dilithio- (6a) and 2,7-bis(bromomagnesio)- (6b) naphthalenes
      with a number of electrophiles, new "proton sponge" derivatives 7a-e,g,
      containing iodo, methylthio, trimethylsilyl, methyl, n-butyl, and ethoxycarbonyl
      groups in ortho-positions to dimethylamino groups, have been synthesized. The
      investigation of their molecular structure, spectral characteristics, and
      basicity reveals that the latter is mainly determined by two groups of factors:
      (1) the polar effect of ortho-substituents and (2) the so-called "buttressing
      effect" representing the complex combination of various sterical interactions of
      ortho-substituents with dimethylamino groups in corresponding bases and cations.
      A contradictory directionality of these interactions strongly reduces the
      importance of the buttressing effect in the case of compounds with bulky ortho
      substituents, which is most clearly displayed in the absence of any relationship
      between the size of ortho-substituents and the basicity. On the contrary, for
      proton sponges having in ortho-positions the electron-donating groups with lesser
      steric demands, both the buttressing and the polar effects act in the same
      direction. This is the reason for the exceptionally high basicity of 2,7
      dimethoxy- (2) and tetrakis(dimethylamino)- (3a) naphthalenes. It has been found
      that bis(trimethylsilyl)-bis(dimethylamino)naphthalene 7d has an in-out
      configuration of the NMe2 groups in the solid that is the first example of its
      kind in the series of naphthalene proton sponges. The origin of a yellow coloring
      of 2,7-disubstituted proton sponges is also discussed.

PMID- 14682709
TI  - Thermolytic properties of 3-(2-pyridyl)-1-propyl and 2-[N-methyl-N-(2
      pyridyl)]aminoethyl phosphate/thiophosphate protecting groups in solid-phase
      synthesis of oligodeoxyribonucleotides.
AB  - Thermolytic groups may serve as alternatives to the conventional 2-cyanoethyl
      group for phosphate/thiophosphate protection in solid-phase oligonucleotide
      synthesis to prevent DNA alkylation by acrylonitrile generated under the basic
      conditions used for oligonucleotide deprotection. Additionally, thermolytic
      groups are attractive in the context of engineering a "heat-driven" process for
      the synthesis of oligonucleotides on diagnostic microarrays. In these regards,
      the potential application of pyridine derivatives as thermolytic
      phosphate/thiophosphate protecting groups has been investigated. Specifically, 2
      pyridinepropanol and 2-[N-methyl-N-(2-pyridyl)]aminoethanol were incorporated
      into deoxyribonucleoside phosphoramidites 7a-d and 9, which were found as
      efficient as 2-cyanoethyl deoxyribonucleoside phosphoramidites in solid-phase
      oligonucleotide synthesis. Whereas the removal of 3-(2-pyridyl)-1-propyl
      phosphate/thiophosphate protecting groups from oligonucleotides is effected
      within 30 min upon heating at 55 degrees C in concentrated NH4OH or in an aqueous
      buffer at pH 7.0, cleavage of 2-[N-methyl-N-(2-pyridyl)]aminoethyl groups occurs
      spontaneously when their phosphate or phosphorothioate esters are formed during
      oligonucleotide synthesis. The deprotection of these groups follows a
      cyclodeesterification process generating the bicyclic salts 13 and 14 as side
      products. These salts do not alkylate or otherwise modify any DNA nucleobases and
      do not desulfurize a phosphorothioate diester model under conditions mimicking
      large-scale oligonucleotide deprotection.

PMID- 14682710
TI  - Role of copper species in the oxidative dimerization of arylboronic acids:
      synthesis of symmetrical biaryls.
AB  - Certain Cu(I) and Cu(II) salts are able to mediate the dimerization of
      arylboronic acids in DMF. They provide the corresponding symmetrical biaryls in
      moderate to very good yields. It is possible to run the reaction catalytically
      under an oxygen atmosphere without a significant loss of yields.

PMID- 14682711
TI  - Synthesis of optically pure arylsilylcarbinols and their use as chiral
      auxiliaries in oxacarbenium ion reactions.
AB  - A family of arylsilylcarbinols was synthesized and investigated as chiral
      auxiliaries for oxacarbenium ion reactions. The optically pure arylsilylcarbinols
      were prepared using Noyori's transfer hydrogenation catalyst 11. The transfer
      hydrogenation shows very good enantioselectivities and turnover efficiency for
      the aryl silyl ketones and is the method of choice for preparing these optically
      pure alcohols. The diastereoselective addition of allyltrimethylsilane to an in
      situ generated oxacarbenium ion was explored using Marko's conditions. The
      selectivity for a representative aliphatic aldehyde was very good, but the
      selectivity was significantly reduced with unsaturated and aromatic aldehydes.
      The range of selectivities with different auxiliaries was narrow, and the most
      practical auxiliary is the phenylsilylcarbinol 2.

PMID- 14682712
TI  - Effect of temperature on the enantioselectivity in the oxazaborolidine-catalyzed
      asymmetric reduction of ketones. Noncatalytic borane reduction, a nonneglectable
      factor in the reduction system.
AB  - The effect of temperature on the enantioselectivity of the oxazaborolidine
      catalyzed asymmetric borane reduction of ketones has been investigated carefully
      using alkyl aryl ketones with a variety of functional groups and a B
      methoxyoxazaborolidine derived from trimethyl borate and (S)-alpha,alpha
      diphenylprolinol as a catalyst. The reductions were carried out over a range of
      temperatures in THF and toluene with or without the catalyst. The reductive rates
      increase along with increasing reaction temperature with or without the catalyst
      by determining the conversion of the ketones to alcohols by GC analysis. However,
      the rates of the catalytic reductions increase faster than those without the
      catalyst. The results indicate that the noncatalytic borane reduction is an
      important factor to the enantioselectivity in the reduction. The highest
      enantioselectivities were usually obtained between 20 and 30 degrees C in the
      asymmetric reduction.

PMID- 14682713
TI  - Addition of lithiated C-nucleophiles to 2,3-O-isopropylidene-D-erythronolactone:
      stereoselective formation of a furanose C-disaccharide.
AB  - Addition of PhLi and lithiated dithianes to 2,3-O-isopropylidene-D
      erythronolactone affords lactols, which are reduced with Et3SiH to the
      corresponding C-glycosides, the structures of two of which have been solved by X
      ray diffraction. The use of a d-ribose-derived lithiated dithiane nucleophile in
      this chemistry allows for the convenient construction of a furanose C
      disaccharide.

PMID- 14682714
TI  - Triton X-100 enhances ion-pair-driven molecular recognition in aqueous media.
      Further work on a chemosensor for inositol trisphosphate.
AB  - Molecular recognition in water based on ion-pairing is hampered by competition
      from the solvent. We have reported that synthetic receptor 1 recognizes inositol
      trisphosphate (IP3) with a binding constant of 10(8) M(-1) in methanol. In this
      paper, instead of working in methanol, we report that the surfactant Triton-X 100
      also yields a large absorbance or fluorescence change and a binding constant on
      the order of 10(6) M(-1).

PMID- 14682715
TI  - Isolation and magnetic properties of heterocycle-carrying N-alkoxyarylaminyl
      radicals.
AB  - Two N-tert-butoxy-2,6-diaryl-4-(4-pyridyl)phenylaminyls (1) and three N-tert
      butoxy-2,6-diaryl-4-(1H-imidazol-1-yl)phenylaminyls (2) were prepared by the
      reaction of the lithium salts of the corresponding anilines with tert-butyl
      peroxybenzoate. Although 1 could not be isolated as radical crystals, 2 was
      successfully obtained as red crystals. The X-ray crystallographic analysis and
      magnetic susceptibility measurements were performed for one isolated radical.

PMID- 14682717
TI  - Improved synthesis of aza-bis(oxazoline) ligands.
AB  - A straightforward synthesis of chiral aza-bis(oxazoline) (Azabox) ligands from
      commercially available amino alcohols is described. The new protocol allows
      access to previously reported Azabox ligands in considerably improved yields but
      also to new derivatives, including non-C2-symmetrical ones.

PMID- 14682716
TI  - Synthesis of novel lysophosphatidylcholine analogues using serine as chiral
      template.
AB  - Four novel lysophosphatidylcholine (lysoPC) analogues, (S)-N-stearoyl-O
      phosphocholineserine methyl ester [(S)-1a], (R)-1-lyso-2-stearoylamino-2-deoxy-sn
      glycero-3-phosphatidylcholine [(R)-2a], (R)-N-stearoyl-O-phosphocholineserine
      methyl ester [(R)-1b], and (S)-1-lyso-2-stearoylamino-2-deoxy-sn-glycero-3
      phosphatidylcholine [(S)-2b], were synthesized starting from serine as a chiral
      template. These synthetic compounds exhibited greatly enhanced hyphal transition
      inhibitory activity in Candida as compared to the natural lysoPC.

PMID- 14682718
TI  - New efficient procedure for the use of diethoxyphosphoryl as a protecting group
      in the synthesis of polyazamacrocycles. Preparation of polyazacyclophanes derived
      from resorcinol.
AB  - The synthesis of polyazamacrocycles containing an electron-rich aromatic subunit
      derived from resorcinol is described. The reported synthetic procedure is based
      on the use of diethoxyphosphoryl (Dep) as an amine protecting group. The new
      conditions employed for the cyclization reaction allow for a generalized use of
      Dep in the synthesis of polyazamacrocycles.

PMID- 14682719
TI  - Novel synthesis of 2-oxo-3-butynoates by copper-catalyzed cross-coupling reaction
      of terminal alkynes and monooxalyl chloride.
AB  - A general and efficient Cu(I)-catalyzed cross-coupling reaction of terminal
      alkynes and monooxalyl chloride for the synthesis of 2-oxo-3-butynoates and 2-oxo
      3-butynoamides was developed. Readily available starting materials, the mild
      reaction conditions, wide functional group tolerance, and the obviation of
      stoichiometric organolithium or magnesium reagents combine to highlight this
      reaction.

PMID- 14682720
TI  - Reaction of alkynes with iodine monochloride revisited.
AB  - 6-Exo-dig and/or 7-endo-dig iodocyclization reactions of functionalized
      acetylenic derivatives with ICl are disfavored in comparison with the
      corresponding electrophilic addition reactions providing regioselectively (E)-1
      chloro-2-iodoethene derivatives. On the contrary, 6-endo-digand 5-exo-dig
      iodocyclizations of methyl ynoates with ICl seem to be favored in comparison with
      the corresponding electrophilic addition reactions.

PMID- 14682721
TI  - An efficient two-step total synthesis of the quaterpyridine nemertelline.
AB  - Regioselective and univocal Suzuki cross-coupling reactions performed on
      halopyridinyl boronic acids provide a flexible and versatile route to a multigram
      scale synthesis of 2,2'-dichloro-3,4'-bipyridine 14, which allows couplings with
      excess pyridin-3-yl boronic acid to give a new and efficient two-step rapid
      synthesis of nemertelline, the quaterpyridine neurotoxin isolated from a
      Hoplonemertine sea worm.

PMID- 14682722
TI  - Nucleophilic aromatic substitution of methacrylamide anion and its application to
      the synthesis of the anticancer drug bicalutamide.
AB  - The anticancer drug (R,S)-biscaltamide was prepared in three steps in >90%
      overall yield. A key step in the new synthesis involved a new nucleophilic
      aromatic substitution reaction of methacrylamide anion.

PMID- 14682723
TI  - Stereoselective construction of a beta-isopropenyl alcohol moiety at the C(2) and
      (3) of kallolide A and pinnatin a using a [2,3] Wittig rearrangement of cyclic
      furfuryl ethers.
AB  - A stereocontrolled synthesis of anti- and syn-beta-isopropenyl alcohol moieties
      at the C(2)-C(3) positions of kallolide A and pinnatin A was accomplished
      employing the [2,3] Wittig rearrangement of (E)-and (Z)-cyclic furfuryl ethers 8.
      Enantioselective Wittig rearrangement of (E)- and (Z)-furfuryl ethers 8 using
      butyllithium and a chiral bis(oxazoline) was also examined to provide (2R,3R)
      homoallylic alcohol anti-9 in up to 61% ee and (2R,3S)-syn-9 in up to 93% ee,
      respectively.

PMID- 14682724
TI  - Synthesis of enantiomerically enriched oxazolinyl[1,2]oxazetidines.
AB  - The first stereoselective synthesis of oxazolinyl[1,2]oxazetidines based on the
      reaction of lithiated 2-(1-chloroethyl)-2-oxazolines with nitrones is described.
      Highly enantioenriched oxazolinyl[1,2]oxazetidines have also been prepared
      starting from a 1:1 diastereomeric mixture of optically active 2-(1-chloroethyl)
      2-oxazolines.

PMID- 14682725
TI  - Tandem or sequential coupling-IMDA cycloaddition approach to highly fused
      polycarbocycles.
AB  - The Diels-Alder cycloadduct made from 3,5-dibromo-2-pyrone and 2-bromo-styrene
      was successfully transformed stereoselectively into a series of novel
      benzotetracycles via a tandem or sequential Pd-catalyzed coupling-intramolecular
      Diels-Alder (IMDA) cycloaddition. The resulting polycarbocycles can be readily
      converted into a bicyclo[3.3.1]nonane system upon ozonolysis of the internal
      double bond.

PMID- 14682726
TI  - A convenient synthesis of 7-halo-1-indanones and 8-halo-1-tetralones.
AB  - A regioselective oxidation of N-indan-4-yl-acetamide or N-(5,6,7,8
      tetrahydronaphthalen-1-yl)acetamide with potassium permanganate followed by
      acidic hydrolysis gave 7-aminoindan-1-one or 8-aminotetral-1-one in good yield.
      The amino ketones were converted to the corresponding 7-haloindanone or the 8
      halotetralone. Another method to prepare 7-haloindan-1-ones was completed by a
      cyclization of 3-chloro-1-(2-halophenyl)propan-1-one under Friedel-Crafts
      conditions to produce the product in gram quantity.

PMID- 14682729
TI  - Carbomethoxyfluorocarbene.
AB  - Carbomethoxyfluorocarbene was studied in solution by laser flash photolysis with
      UV-vis and infrared detection. In contrast to expectations,
      carbomethoxyfluorocarbene is more reactive than carbomethoxychlorocarbene.
      [structure: see text]

PMID- 14682730
TI  - Rotaxane-stabilized thiophosphonium salt from disulfide and phosphine.
AB  - The reaction of a rotaxanated disulfide with hexamethylphosphorustriamide
      afforded a stable thiophosphonium salt in rotaxanated form. The structure of the
      thioposphonium salt was confirmed by spectroscopic and X-ray crystal structure
      analyses. The successful isolation of this salt was attributed to the special
      stabilization capability of the rotaxane structure. [reaction: see text]

PMID- 14682731
TI  - The palladium(II)-catalyzed Nazarov reaction.
AB  - The PdCl(2)-catalyzed cyclization of alpha-alkoxy dienones leads to 2
      hydroxycyclopentenones, whereas the Pd(OAc)(2)-catalyzed reaction leads to cross
      conjugated cyclopentenones through an oxidative process. [reaction: see text]

PMID- 14682732
TI  - Efficient Nazarov cyclizations of 2-alkoxy-1,4-pentadien-3-ones.
AB  - Expeditious and high-yielding Nazarov cyclizations of 2-alkoxy-1,4-pentadien-3
      ones are described. An example of a catalytic asymmetric Nazarov cyclization is
      presented. [reaction: see text]

PMID- 14682733
TI  - Proofs of macrocyclization of gable porphyrins as mimics of photosynthetic light
      harvesting complexes.
AB  - Porphyrin macrocycles composed of five and six units of m-gable
      imidazolylporphyrinatozinc (1-Zn) were synthesized by self-assembled cyclization
      followed by ring-closing metathesis linkings. Each porphyrin macrocycle was
      isolated by GPC chromatography, and their molecular weights were determined by
      MALDI-TOF mass spectroscopy. These structures represent mimics of light
      harvesting complexes in photosynthetic bacteria. [structure: see text]

PMID- 14682734
TI  - Base-induced photocyclization of 1,2-diaryl-1-tosylethenes. A mechanistically
      novel approach to phenanthrenes and phenanthrenoids.
AB  - The irradiation with UV light of a number of 1,2-diaryl-1-tosylstilbenes, in the
      presence of base, leads to the corresponding phenanthrenes and heterocyclic
      analogues. These results are consistent with a mechanism involving the base
      induced elimination of p-toluenesulfinic acid from an intermediate 9-tosyl-4a,4b
      dihydrophenanthrene, formed by photochemical cyclization of the starting 1,2
      diaryl-1-tosylstilbenes. [reaction: see text]

PMID- 14682735
TI  - Alkoxyamine-mediated radical synthesis of indolinones and indolines.
AB  - Thermolysis of alpha-alkoxyamino propionanilides produces indolinones, whereas
      thermal reaction of N-allylaniline derivatives with various Tordo-type
      alkoxyamines results in formation of indolines in the radical regime. [reaction:
      see text]

PMID- 14682736
TI  - Direct carbamoylation of alkenyl halides.
AB  - Alkenyl chlorides and bromides are converted into tertiary enamides by treatment
      with a carbamoylsilane in toluene at 110 degrees C in the presence of phosphine
      palladium(0) catalysts. [reaction: see text]

PMID- 14682737
TI  - Stereochemical features of the physical and chemical interactions of singlet
      oxygen with enecarbamates.
AB  - Oxazolidinone-substituted enecarbamates represent a mechanistically rich system
      for the study of stereoelectronic, steric, and conformational effects on
      stereoselectivity and mode selectivity in (1)O(2) [2 + 2] and ene reactions.
      Photooxygenation of these enecarbamates with (1)O(2) leads to diastereomerically
      pure dioxetanes that decompose to yield an oxazolidinone carbaldehyde and one of
      the two enantiomers of methyldesoxybenzoin in enantiomeric excess.
      Stereoselectivity originates at the allylic stereocenter, a result supported by
      quenching studies, computational analysis, and deuterium solvent isotope effects.
      [reaction: see text]

PMID- 14682738
TI  - cis- and trans-stereoselective epoxidation of N-protected 2-cyclohexen-1
      ylamines.
AB  - The first systematic study of the cis and trans stereoselectivity in the m-CPBA
      epoxidation of N-protected cyclic allylic amines has been completed. Mono-N
      protected systems gave epoxides with cis stereochemistry (amides are better cis
      directors than sulfonamides or carbamates) whereas di-N-protected systems gave
      trans-epoxides (TsNBoc protection gave complete trans stereoselectivity).
      [structure: see text]

PMID- 14682739
TI  - Toward a total synthesis of peloruside A: enantioselective preparation of the C8
      C19 region.
AB  - An efficient synthetic sequence toward the C8-C19 region of peloruside A has been
      developed. The route is highlighted by a selective electrophilic cyclization
      reaction, a single-step epoxide ring-opening/methylation sequence, and a
      stereoselective Mukaiyama aldol reaction. [reaction: see text]

PMID- 14682740
TI  - Tetraorganoindates as nucleophilic coupling partners in Pd-catalyzed cross
      coupling reactions.
AB  - In situ-generated tetraorganoindate complexes from the reaction of 1 equiv of
      indium trichloride with 4 equiv of appropriate organometallics are efficient
      nucleophiles in Pd-catalyzed cross-coupling reactions. In this novel reaction
      tetraorganoindates containing methyl, 1 degree- and 2 degree-alkyl, vinyl,
      alkynyl, and aryl groups transfer the four organic groups to a variety of
      electrophiles with high atom efficiency. [reaction: see text]

PMID- 14682741
TI  - Immobilized cobalt/rhodium heterobimetallic nanoparticle-catalyzed
      silylcarbocylization and carbonylative silylcarbocyclization of 1,6-enynes.
AB  - Reaction of 1,6-enynes with a hydrosilane in the presence of immobilized
      cobalt/rhodium bimetallic nanoparticles gives 2-methyl-1-silylmethylidene-2
      cyclopentanes in the absence of carbon monoxide and 2-formylmethyl-1
      silylmethylidene-2-cyclopentanes under 1 atm of carbon monoxide, respectively.
      [reaction: see text]

PMID- 14682742
TI  - A novel ditopic receptor and reversal of anion binding selectivity in the
      presence and absence of bound cation.
AB  - A calix[4]arene-derived ditopic receptor 1 has been synthesized. In the absence
      of Na+, the receptor binds acetate in preference to diphenyl phosphate (as the
      tetrabutylammonium salts), but in the presence of Na+, the selectivity is
      reversed and the receptor, instead, binds diphenyl phosphate, and not acetate,
      which preferentially forms a salt ion-pair in free solution. [structure: see
      text]

PMID- 14682743
TI  - New set of orthogonal protecting groups for the modular synthesis of heparan
      sulfate fragments.
AB  - Six strategically chosen monosaccharide building blocks, which are protected by a
      novel set of four orthogonal protecting groups (Lev, Fmoc, TBDPS, and All), can
      be employed for the efficient synthesis of the 20 disaccharide moieties found in
      heparan sulfate. The properly protected disaccharide building blocks can be
      converted into glycosyl donors and acceptors, which can be used for the modular
      synthesis of a wide range of well-defined oligosaccharides that differ in
      sulfation pattern. [structure: see text]

PMID- 14682744
TI  - Zeolite-promoted oxidations of 1,1-diarylethylenes.
AB  - The intrazeolite photooxygenations of four diarylethylenes have been examined.
      Several intermediates, including an epoxide, have been identified by comparison
      to independently synthesized samples. Aldehyde intermediates were shown to
      undergo intrazeolite Norrish type I cleavages in competition with a novel new
      photooxygenation/autoxidation reaction. [reaction: see text]

PMID- 14682745
TI  - Studies on the synthesis of gymnodimine. construction of the spiroimine portion
      via Diels-Alder cycloaddition.
AB  - An azaspiro[5.5]undecadiene corresponding to a subunit of the shellfish toxin
      gymnodimine was synthesized by Diels-Alder cycloaddition. One member of the pair
      of stereoisomeric adducts was transformed to a spiroimine, which will serve as
      the core around which the macrocyclic portion of the toxin will be assembled.
      [structure: see text]

PMID- 14682746
TI  - Synthesis of secondary arylamines through copper-mediated intermolecular aryl
      amination.
AB  - A mild intermolecular copper-mediated amination of aryl iodides has been
      developed. The reaction takes place at room temperature or heating at 90 degrees
      C and tolerates halogens attached to the aromatic ring. Its synthetic
      applications include a synthetic protocol for unsymmetrical N,N'-dialkylated
      phenylenediamines and both a stepwise and a general synthetic method for N-aryl
      secondary amines via Ns-anilides (readily obtained by reaction of the Ns-amide).
      [reaction: see text]

PMID- 14682747
TI  - Gallium(III) chloride-catalyzed double insertion of isocyanides into epoxides.
AB  - Gallium(III) chloride-catalyzed double insertion of aryl isocyanides into
      terminal and disubstituted epoxides leads to alpha,beta-unsaturated alpha-amino
      iminolactones (3-amino-2-iminio-2,5-dihydrofurans). [reaction: see text]

PMID- 14682748
TI  - Trichloro-oxazolines as activated donors for aminosugar coupling.
AB  - Starting from tri-O-acetyl-D-glucal, a combination of the Overman rearrangement
      and subsequent dihydroxylation produces a range of aminosugars. These can be
      activated by formation of the corresponding trichloro-oxazolines, which are
      excellent glycosyl donors as they form disaccharides with good (trans)
      stereoselectivity under mild conditions. Propagation of these trichloro
      oxazolines gave trisaccharides that can then be dehalogenated under a variety of
      conditions. [reaction: see text]

PMID- 14682749
TI  - Ring expansive routes to quinolizidine alkaloids: formal synthesis of (-)
      lasubine II.
AB  - The application of two nitrogen ring expansion reactions to lasubine alkaloid
      synthesis is reported. The approach involves a conjugate reduction/alkylation
      sequence carried out on triisopropylsilyl-protected (S)-4-(-)
      hydroxycyclopentenone, the formation of the quinolizidone ring system through
      nitrogen ring expansion, and the addition of an arylmetallic species to the
      resulting lactam. This work resulted in the preparation of 2-epi-lasubine II and
      a formal synthesis of lasubine II. [reaction: see text]

PMID- 14682750
TI  - Exploration of ionic liquids as soluble supports for organic synthesis.
      Demonstration with a Suzuki coupling reaction.
AB  - The efficiency of ionic liquid supported synthesis was demonstrated by the Suzuki
      reaction of ionic liquid supported iodobenzoate compounds with arylboronic acids
      in aqueous media to give, after cleavage with ammonia/methanol, biaryl products
      in good yields and high purities, without the need for chromatographic
      purification. [reaction: see text]

PMID- 14682751
TI  - Postcolumn HPLC detection of mono- and oligosaccharides with a chemosensor.
AB  - Novel chromophoric compound 1 promotes the HPLC postcolumn detection of mono- and
      oligosaccharides. The detection of chromatographic peaks in the visible region
      for glucose, fructose, maltodextrins, sialic acid, and a ganglioside can be
      accomplished with a standard UV-vis detector. The use of selective, reversible
      binding agents in automated HPLC assays should allow for improved monitoring of
      specific analytes as well as material recovery. [structure: see text]

PMID- 14682752
TI  - Direct asymmetric synthesis of beta-amino ketones from sulfinimines (N
      sulfinylimines). Synthesis of (-)-indolizidine 209B.
AB  - N-Sulfinyl beta-amino ketones, prepared directly from the potassium enolates of
      methyl ketones and enantiopure sulfinimines, are transformed in one pot to
      protected amino ketones, which are valuable chiral building blocks for the
      assembly of piperidines. The utility of this methodology is illustrated in a
      concise asymmetric synthesis of (-)-indolizidine 209B. [reaction: see text]

PMID- 14682753
TI  - Further utilization of mucohalic acids: palladium-free, regioselective
      etherification and amination of alpha,beta-dihalo gamma-methoxycarbonyloxy and
      gamma-acetoxy butenolides.
AB  - Palladium-free etherification and amination of mucohalic acid methyl carbonates
      1e (3,4-dichloro-5-methoxycarbonyloxy-5H-furan-2-one) and 1f (3,4-dibromo-5
      methoxycarbonyloxy-5H-furan-2-one) and mucochloric acid acetate 1h (3,4-dichloro
      5-acetoxy-5H-furan-2-one) was achieved to afford gamma-functionalized alpha,beta
      unsaturated gamma-butyrolactones in good to excellent yield. [reaction: see text]

PMID- 14682754
TI  - Studies toward the synthesis of oximidines I and II.
AB  - The synthesis of compound 1, a precursor for the synthesis of the oximidine II
      core structure 2, is described. An undesired C8-C9 isomerization occurred during
      the intramolecular Castro-Stephens reaction leading to macrocyle 3. The
      thermodynamic driving force for this unexpected isomerization was established by
      DFT and MP2 calculations. [reaction: see text]

PMID- 14682755
TI  - Concise and efficient synthesis of 4-fluoro-1H-pyrrolo[2,3-b]pyridine.
AB  - Two routes describing the preparation of 4-fluoro-1H-pyrrolo[2,3-b]pyridine (4a)
      from 1H-pyrrolo[2,3-b]pyridine N-oxide (1) are presented. Regioselective
      fluorination was achieved using either the Balz-Schiemann reaction or lithium
      halogen exchange. [reaction: see text]

PMID- 14682756
TI  - Aryloxy radicals from diaryloxydiazirines: alpha-cleavage of diaryloxycarbenes or
      excited diazirines?
AB  - The synthesis of diaryloxydiazirines, precursors to diaryloxycarbenes, is
      described. Thermolyses of the diazirines afford anticipated carbene products, but
      photolyses afford both carbenes and aryloxy radicals by alpha-scission. UV
      spectra of the carbenes and radicals are observed. [reaction: see text]

PMID- 14682757
TI  - Deletion of the oxetane ring in docetaxel analogues: synthesis and biological
      evaluation.
AB  - Two new docetaxel analogues have been prepared starting from 10-deacetylbaccatin
      III. Both derivatives lack the oxetane D-ring but possess the 4alpha-acetoxy
      group, which is important for biological activity. The influence of a more or
      less constrained C-ring was evaluated by adding, or not adding, a double bond in
      this ring. Both compounds were found to be equally less active than docetaxel in
      biological assays. [reaction: see text]

PMID- 14682758
TI  - Leucascandrolide A: a second generation formal synthesis.
AB  - A convergent, second generation formal synthesis of (+)-Leucascandrolide A (1)
      has been efficiently achieved by providing a flexible, enantiocontrolled strategy
      toward the bioactive macrolactone component. Advancements for stereocontrol in
      asymmetric allylation methodology are discussed. Efforts feature novel results
      for reductions using the Terashima hydride reagent. [structure: see text]

PMID- 14682759
TI  - Highly enantioselective hydrogenation of aromatic-heteroaromatic ketones.
AB  - Asymmetric hydrogenation of ketone 1 using trans-RuCl(2)[(R)-xylbinap][(R)
      daipen] (3) as a catalyst afforded secondary alcohol 2 quantitatively and in
      99.4% ee. Further exploration of the effect of the thiazole ring substitution
      revealed that the catalyst was highly effective for the enantioselective
      hydrogenation of 5-benzoyl thiazoles, which afforded corresponding alcohols in 92
      99% ee. The same protocol was applicable to a variety of aromatic-heteroaromatic
      ketones to generate secondary alcohols in excellent enantioselectivities.
      [reaction: see text]

PMID- 14682760
TI  - exo- and enantioselective cycloaddition of azomethine ylides generated from N
      alkylidene glycine esters using chiral phosphine-copper complexes.
AB  - High diastereo- and enantioselectivities were obtained for the asymmetric 1,3
      dipolar cycloaddition of azomethine ylides generated from N-alkylideneglycine
      esters with dipolarophiles using chiral phosphine-copper complexes as catalysts.
      Whereas the cycloaddition of azomethine ylides catalyzed by metal salts generally
      afforded endo-adducts as the predominant product, the present method is the first
      example of an exo-selective cycloaddition. [reaction: see text]

PMID- 14682761
TI  - Synthesis of the chlorofusin cyclic peptide: assignment of the asparagine
      stereochemistry.
AB  - An efficient synthesis of two diastereomers of the chlorofusin cyclic peptide
      bearing either the l-Asn3/d-Asn-4 or d-Asn3/l-Asn4 stereochemistry is detailed.
      Four key subunits were prepared, sequentially coupled, and cyclized to provide
      the two diastereomeric macrocycles. The absolute stereochemistry at the
      asparagine residues 3 and 4 was assigned as l and d, respectively, by correlating
      the NMR data of the two diastereomers with that reported for the natural product.
      [structure: see text]

PMID- 14682762
TI  - Solid-phase synthesis of the cyclic peptide portion of chlorofusin, an inhibitor
      of p53-MDM2 interactions.
AB  - The first solid-phase synthesis of the chlorofusin peptide is described. The
      synthesis involved side-chain immobilization of N(alpha)-Fmoc-Asp-ODmab.
      Synthesis of the linear peptide, initially incorporating racemic Ade8 and
      unsubstituted ornithine in place of the chromophore-bearing residue, was followed
      by cyclization on resin and peptide release to give a mixture of diastereomers.
      Resynthesis identified (by HPLC) the second isomer as analogous to the natural
      product. Initial biological assays, using an immunofluorescence method, suggest
      that the compounds are not cytotoxic but do not inhibit the p53/mdm2 interaction.
      [structure: see text]

PMID- 14682763
TI  - Direct detection of ion pair formation and collapse in a migration reaction of a
      beta-phosphate radical.
AB  - In solutions of trifluorotoluene or toluene containing 2,2,2-trifluoroethanol,
      the beta-phosphate radical heterolyzed to give a detectable ion pair, identified
      as a solvent-separated species. Rate constants for the radical fragmentation
      reaction forming the ion pair, for ion pair collapse, and for diffusive escape to
      free ions were measured. The kinetics and entropy of activation for fragmentation
      indicate that the rearrangement reaction occurs by a heterolysis pathway in all
      solvents. [reaction: see text]

PMID- 14682764
TI  - Phenylenebis(ethynyl)-tethered bis-BINOL ligands for enantioselective catalyst
      based on dimeric TiIV aggregate.
AB  - Bis-BINOLs 7a-c in which two BINOL units are tethered by phenylenebis(ethynyl)
      groups react with titanium tetraisopropoxide (2 equiv) to form intramolecular
      dimeric titanium(IV) aggregates 2a-c. Of these, 2a,b with an o
      phenylenebis(ethynyl) tether are stable in the presence of excess titanium
      tetraisopropoxide. Complex 2a exhibits a relatively high enantioselectivity in
      asymmetric addition of diethylzinc to an aldehyde. [structure: see text]

PMID- 14682765
TI  - Preparation of syn-delta-hydroxy-beta-amino esters via an intramolecular hydrogen
      bond directed diastereoselective hydrogenation. Total synthesis of (3S,4aS,6R,8S)
      hyperaspine.
AB  - Hydrogenation of delta-hydroxy-beta-ketoester-derived enamines 8 produces syn
      delta-hydroxy-beta-amino esters 9 diastereoselectively, which may be directed by
      the formation of an intramolecular hydrogen bond between the delta-hydroxyl and
      beta-amino groups. By using this method and a Dieckmann reaction as the key
      steps, (3S,4aS,6R,8S)-hyperaspine, a new type of ladybird alkaloid, is
      synthesized. [reaction: see text]

PMID- 14682766
TI  - Efficient synthesis of (+/-)-erysotramidine using an NBS-promoted cyclization
      reaction of a hexahydroindolinone derivative.
AB  - An NBS-promoted intramolecular electrophilic aromatic substitution reaction of a
      hexahydroindolinone derivative was used to assemble the tetracyclic core of the
      erythrinane skeleton. The resulting cyclized product was transformed into (+/-)
      erysotramidine in three additional steps. The cyclization reaction is also
      successful using variously substituted aryl and furanyl bicyclic lactams under
      acidic conditions. [reaction: see text]

PMID- 14682767
TI  - Supramolecular structures formed by calix[8]arene derivatives.
AB  - Octamethoxy calix[8]arenes substituted in the para position by amide, urea, and
      imide functions were synthesized from the octamethyl ether of tert
      butylcalix[8]arene by ipso nitration, reduction, and acylation. Scanning force
      microscopy of spin coated samples on graphite suggests that these derivatives
      self-organize into tubular nanorods via hydrogen bonds between p-amide functions.
      A single-crystal X-ray structure reveals a centrosymmetric conformation for the
      octanitro derivative. [structure: see text]

PMID- 14682768
TI  - Catalytic asymmetric Nazarov reactions promoted by chiral Lewis acid complexes.
AB  - Divinyl ketones bearing alpha-ester or alpha-amide groups undergo Nazarov
      cyclizations to give cylopentenones using copper-bisoxazoline Lewis acid
      complexes with moderate to good ees. [reaction: see text]

PMID- 14682769
TI  - Cyclic tetrapeptides bearing a sulfhydryl group potently inhibit histone
      deacetylases.
AB  - New inhibitors of histone deacetylase (HDAC) containing a sulfhydryl group were
      designed on the basis of the corresponding hydroxamic acid (CHAP31) and FK228.
      Their disulfide dimers and hybrids exhibited potent HDAC inhibitory activity in
      vivo with potential as anticancer prodrugs. [structure: see text]

PMID- 14682770
TI  - 4,6,8,10,16-penta- and 4,6,8,10,16,18-hexamethyldocosanes from the cane beetle
      antitrogusparvulus--cuticular hydrocarbons with unprecedented structure and
      stereochemistry.
AB  - The major cuticular hydrocarbons from the cane beetle species Antitrogus parvulus
      were deduced to be 4,6,8,10,16,18-hexa- and 4,6,8,10,16-pentamethyldocosanes 2
      and 3, respectively. Isomers of 2,4,6,8-tetramethylundecanal 27, 36, and 37,
      derived from 2,4,6-trimethylphenol, were coupled with the phosphoranes 28 and 29
      to furnish alkenes and, by reduction, diastereomers of 2 and 3. Chromatographic
      and spectroscopic comparisons confirmed 2 as either 6a or 6b and 3 as either 34a
      or 34b. [structure: see text]

PMID- 14682771
TI  - Regio- and stereoselective synthesis of novel (E)-1-alkenyl carbamate via
      carbocupration reaction.
AB  - The stereoselective carbocupration and copper-catalyzed carbomagnesiation
      reactions of alkynyl carbamates are described as a new and straightforward method
      for the preparation of (E)-alkenyl enol carbamates. [reaction: see text]

PMID- 14682772
TI  - Intracellular compartmentation in the biosynthesis of caulerpenyne: study on
      intact macroalgae using stable-isotope-labeled precursors.
AB  - The biosynthesis of caulerpenyne 1 was studied in the invasive green alga
      Caulerpa taxifolia. The investigation was performed on intact algae with stable
      isotope-labeled precursors administered under mixotrophic growth conditions.
      According to the labeling pattern, after incorporation of 1-(13)C-acetate and
      (13)CO(2), respectively, the biosynthesis of the sesquiterpene backbone occurs in
      the chloroplast and follows the methyl-erythritol-4-phosphate (MEP) pathway. In
      contrast, the acetyl residues of caulerpenyne 1 are derived from a cytosolic
      resource. [structure: see text]

PMID- 14682773
TI  - Radical cyclization cascade involving ynamides: an original access to nitrogen
      containing heterocycles.
AB  - A radical cascade involving a 5-exo-dig cyclization followed by a 6-endo-trig
      radical trapping transforms ynamides into heterogeneous polycyclic compounds in
      good yields. This leads interestingly to the formation of isoindols,
      isoindolinones, and pyridoisoindolones. [reaction: see text]

PMID- 14682774
TI  - A powerful new strategy for diversity-oriented synthesis of pyrroles from donor
      acceptor cyclopropanes and nitriles.
AB  - Lewis acid activated donor-acceptor cyclopropanes react with aliphatic, aromatic,
      and alpha,beta-unsaturated nitriles in a novel cascade [3 + 2] dipolar
      cycloaddition, dehydration, and tautomerization sequence to afford pyrroles in
      moderate to excellent overall yield. This cost-effective and regiospecific method
      is ideally suited for the preparation of combinatorial libraries. [reaction: see
      text]

PMID- 14682777
TI  - Persistence of a particle in the Matheron-de Marsily velocity field.
AB  - We show that the longitudinal position x(t) of a particle in a (d+1)-dimensional
      layered random velocity field (the Matheron-de Marsily model) can be identified
      as a fractional Brownian motion (fBm) characterized by a variable Hurst exponent
      H(d)=1-d/4 for d<2 and H(d)=1/2 for d>2. The fBm becomes marginal at d=2.
      Moreover, using the known first-passage properties of fBm we prove analytically
      that the disorder averaged persistence [the probability of no zero crossing of
      the process x(t) up to time t], has a power-law decay for large t with an
      exponent theta=d/4 for d<2 and theta=1/2 for d>/=2 (with logarithmic correction
      at d=2), results that were earlier derived by Redner based on heuristic arguments
      and supported by numerical simulations.

PMID- 14682778
TI  - Dynamics and scaling of two-dimensional polymers in a dilute solution.
AB  - The breakdown of dynamical scaling for a dilute polymer solution in two
      dimensions has been suggested by Shannon and Choy [Phys. Rev. Lett. 79, 1455
      (1997)]. However, we show here through extensive computer simulations that
      dynamical scaling holds when the relevant dynamical quantities are properly
      extracted from finite systems. To verify dynamical scaling, we present results
      based on mesoscopic simulations in two dimensions for a polymer chain in a good
      solvent with full hydrodynamic interactions. We also present analytical arguments
      for the size dependence of the diffusion coefficient and find excellent agreement
      with the present large-scale simulations.

PMID- 14682779
TI  - Self-similarity in random collision processes.
AB  - Kinetics of collision processes with linear mixing rules are investigated
      analytically. The velocity distribution becomes self-similar in the long-time
      limit and the similarity functions have algebraic or stretched exponential tails.
      The characteristic exponents are roots of transcendental equations and vary
      continuously with the mixing parameters. In the presence of conservation laws,
      the velocity distributions become universal.

PMID- 14682780
TI  - Numerical simulations of air-driven granular separation.
AB  - Recently it has been shown that binary mixtures of equal-sized fine granular
      materials exhibit spontaneous separation under vertical vibration in the presence
      of air [Science 295, 1877 (2002)]. Here we describe a model of this behavior
      based on soft-sphere molecular dynamics coupled to the motion of the surrounding
      air. It exhibits many of the features observed experimentally including almost
      complete separation of the components into well defined regions with extremely
      sharp boundaries. The basic separation mechanism is robust and insensitive to
      many of the model parameters. Our results show that the forced flow of air
      through the bed, induced by vibration of the container, is responsible for this
      form of separation.

PMID- 14682781
TI  - Long-range interaction and heterogeneity yield a different kind of critical
      phenomenon.
AB  - DNA denaturation, wetting in two dimensions, depinning of a flux line, and other
      problems are known to map onto a phase transition with effective long-range
      interaction. In a disordered system the latter yields a giant, nonuniversal,
      temperature-dependent critical index, and macroscopic fluctuations at a finite
      distance from the critical temperature. In the vicinity of the critical region
      the Gibbs distribution is invalid, and thermodynamics must be calculated from
      first principles. There are no fluctuations above the critical temperature.

PMID- 14682782
TI  - Stimulated diffusion of an adsorbed dimer.
AB  - The mobility and the diffusivity of a dimer (two atoms coupled by an elastic
      spring) in a periodic substrate potential under the action of the dc and ac
      external forces are studied. It is shown that the dimer diffusivity may be
      strongly enhanced due to driving.

PMID- 14682783
TI  - Effects of cross correlation on the relaxation time of a bistable system driven
      by cross-correlated noise.
AB  - We study the effects of correlations between additive and multiplicative noise on
      relaxation time in a bistable system driven by cross-correlated noise. Using the
      projection-operator method, we derived an analytic expression for the relaxation
      time T(c) of the system, which is the function of additive (alpha) and
      multiplicative (D) noise intensities, correlation intensity lambda of noise, and
      correlation time tau of noise. After introducing a noise intensity ratio and a
      dimensionless parameter R=D/alpha, and then performing numerical computations, we
      find the following: (i) For the case of R<1, the relaxation time T(c) increases
      as R increases. (ii) For the cases of R>/=1, there is a one-peak structure on the
      T(c)-R plot and the effects of cross-correlated noise on the relaxation time are
      very notable. (iii) For the case of R<1, T(c) almost does not change with both
      lambda and tau, and for the cases of R>/=1, T(c) decreases as lambda increases,
      however T(c) increases as tau increases. lambda and tau play opposite roles in
      T(c), i.e., lambda enhances the fluctuation decay of dynamical variable and tau
      slows down the fluctuation decay of dynamical variable.

PMID- 14682785
TI  - Weak nonlinear surface-charging effects in electrolytic films.
AB  - A simple model of soap films with nonionic surfactants stabilized by added
      electrolyte is studied. The model exhibits charge regularization due to the
      incorporation of a physical mechanism responsible for the formation of a surface
      charge. We use a Gaussian field theory in the film but the full nonlinear surface
      terms which are then treated at a one-loop level by calculating the mean-field
      Poisson-Boltzmann solution and then the fluctuations about this solution. We
      carefully analyze the renormalization of the theory and apply it to a triple
      layer model for a thin film with Stern layer of thickness h. For this model we
      give expressions for the surface charge sigma(L) and the disjoining pressure
      P(d)(L) and show their dependence on the parameters. The influence of image
      charges naturally arises in the formalism, and we show that predictions depend
      strongly on h because of their effects. In particular, we show that the surface
      charge vanishes as the film thickness L-->0. The fluctuation terms in this class
      of theories contribute a Casimir-like attraction across the film. Although this
      attraction is well known to be negligible compared with the mean-field component
      for model electrolytic films with no surface-charge regulation, in the model
      studied here these fluctuations also affect the surface-charge regulation leading
      to a fluctuation component in the disjoining pressure which has the same behavior
      as the mean-field component even for large film thickness.

PMID- 14682784
TI  - Effect of a columnar defect on the shape of slow-combustion fronts.
AB  - We report experimental results for the behavior of slow-combustion fronts in the
      presence of a columnar defect with enhanced or reduced driving, and compare them
      with those of mean-field theory. We also compare them with simulation results for
      an analogous problem of driven flow of particles with hard-core repulsion (ASEP)
      and a single defect bond with a different hopping probability. The difference in
      the shape of the front profiles for enhanced vs reduced driving in the defect
      clearly demonstrates the existence of a Kardar-Parisi-Zhang-type nonlinear term
      in the effective evolution equation for the slow-combustion fronts. We also find
      that slow-combustion fronts display a faceted form for large enough enhanced
      driving, and that there is a corresponding increase then in the average front
      speed. This increase in the average front speed disappears at a nonzero enhanced
      driving in agreement with the simulated behavior of the ASEP model.

PMID- 14682786
TI  - Damped finite-time singularity driven by noise.
AB  - We consider the combined influence of linear damping and noise on a dynamical
      finite-time singularity model for a single degree of freedom. We find that the
      noise effectively resolves the finite-time singularity and replaces it by a first
      passage-time distribution or absorbing state distribution with a peak at the
      singularity and a long time tail. The damping introduces a characteristic cross
      over time. In the early time regime the probability distribution and first
      passage-time distribution show a power law behavior with scaling exponent
      depending on the ratio of the nonlinear coupling strength to the noise strength.
      In the late time regime the behavior is controlled by the damping. The study
      might be of relevance in the context of hydrodynamics on a nanometer scale, in
      material physics, and in biophysics.

PMID- 14682787
TI  - Dynamics of randomly branched polymers: configuration averages and solvable
      models.
AB  - Treating the relaxation dynamics of an ensemble of random hyperbranched
      macromolecules in dilute solution represents a challenge even in the framework of
      Rouse-type approaches, which focus on generalized Gaussian structures (GGSs). The
      problem is that one has to average over a large class of realizations of
      molecular structures, and that each molecule undergoes its own dynamics. We show
      that a replica formalism allows to develop analytically, based on an integral
      equation, a systematic way to determine the ensemble averaged eigenvalue
      spectrum. Interestingly, for a specific probability distribution of the spring
      strengths of the GGSs, the integral equation takes a particularly simple form.
      Given that several dynamical observables, such as the mechanical moduli G'(omega)
      and G"(omega), as well as the averaged monomer displacement <Y(t)> are relatively
      simple functions of the eigenvalues, we can use the obtained spectra to compute
      the corresponding averaged dynamical forms. Comparing the results obtained from
      this approach and from extensive diagonalizations of hyperbranched GGSs we find a
      very good agreement.

PMID- 14682788
TI  - Diffusion time-scale invariance, randomization processes, and memory effects in
      Lennard-Jones liquids.
AB  - We report the results of calculation of diffusion coefficients for Lennard-Jones
      liquids, based on the idea of time-scale invariance of relaxation processes in
      liquids. The results were compared with the molecular dynamics data for the
      Lennard-Jones system and a good agreement of our theory with these data over a
      wide range of densities and temperatures was obtained. By calculations of the non
      Markovity parameter we have numerically estimated statistical memory effects of
      diffusion in detail.

PMID- 14682789
TI  - Structural transitions and nonmonotonic relaxation processes in liquid metals.
AB  - Structural transitions in melts as well as their dynamics are considered. It is
      supposed that liquid represents the solution of relatively stable solidlike
      locally favored structures in the surrounding of disordered normal-liquid
      structures. Within the framework of this approach the step changes of liquid Co
      viscosity are considered as liquid-liquid transitions. It is supposed that this
      sort of transition represents the cooperative medium-range bond ordering, and
      corresponds to the transition of the "Newtonian fluid" to the "structured fluid."
      It is shown that relaxation processes with oscillatinglike time behavior (omega
      approximately 10(-2) s(-1)) of viscosity are possibly close to this point.

PMID- 14682790
TI  - Effect of external electric field on the bulk and interfacial properties of
      weakly dipolar fluid in slab-shaped and sphere-shaped systems.
AB  - The effect of a uniform electric field on the bulk and interfacial properties of
      a model dipolar fluid is investigated by using a modified mean-field density
      functional theory. Particular attention is given to the dependence of the vapor
      liquid phase coexistence in a slab-shaped system on the direction of the electric
      field with respect to the slab surfaces, as well as in the sphere-shaped system
      on the surrounding dielectric permittivity. For planar vapor-liquid interfaces,
      the interfacial profiles of the orientation order parameters and components of
      the dielectric-permittivity tensor are calculated. Analytical expressions for
      these interfacial profiles and their dependence on the electric field are
      obtained. When the electric field is normal to the interface we find that the
      thermodynamic surface tension is lowered compared to that in zero field, and that
      when the electric field is parallel to the interface the surface tension is
      enhanced. In contrast, the mechanical surface tension at the equimolar dividing
      surface is always enhanced by the field regardless of the field direction, and it
      assumes its highest value when the field is parallel to the interface.

PMID- 14682791
TI  - Theory of the viscosity of supercooled liquids and the glass transition: fragile
      liquids.
AB  - A statistical mechanical theory is presented for viscosity of relatively low
      molecular weight organic liquids which are supercooled down to the glass
      transition temperature. In this theory a relation resembling the Stokes-Einstein
      relation between the viscosity and self-diffusion coefficient of supercooled
      liquids and an expression for the self-diffusion coefficient are augmented by a
      suitably constructed semiempirical generic van der Waals equation of state that
      makes it possible to calculate the free volume. The theory accounts in excellent
      accuracy for viscosities and self-diffusion coefficients of fragile liquids over
      the entire range of temperature experimentally investigated. According to the
      theory, vitrification occurs when the free volume available for translational
      molecular motion falls below a critical value.

PMID- 14682792
TI  - Compaction force in a confined granular column.
AB  - Experiments to determine the force required to push a granular column confined
      within a cylinder were performed. The experimental apparatus was mounted on a
      material testing system machine in order to obtain force and displacement
      measurements simultaneously. Experiments were performed for two different sphere
      diameters, two different cylinder diameters and for a range of piston
      displacement velocities. The force necessary to displace the column increases
      rapidly with the column height, in accordance with Janssen's theory. More
      importantly, we found that this force also increases with the displacement
      velocity. This unexpected behavior is an indication of the transition to rate
      dependent behavior in dense granular flows.

PMID- 14682793
TI  - Closed model for granular compaction under weak tapping.
AB  - A one-dimensional lattice model is formulated to study tapping dynamics and the
      long time steady distribution in granular media. The dynamics conserves the
      number of particles in the system, and density changes are associated with the
      creation and destruction of empty sites. The model is shown to be consistent with
      Edwards' thermodynamics theory of powders. The relationship with lattice models
      in which the number of particles is not conserved is discussed.

PMID- 14682794
TI  - Two-dimensional inclined chute flows: transverse motion and segregation.
AB  - We present an experimental study of two-dimensional dense inclined chute flows
      consisting of both monodisperse and bidisperse disks. We analyzed the
      trajectories of the particles within the flow in a steady regime. (i) In
      monodisperse flows, particles are arranged in layers that are in motion relative
      to one another, and it is found that the particles have a nonzero probability of
      being transferred to adjacent layers. We measured the mean time spent by a
      particle in a given layer. This residence time is found to decrease with
      increasing layer height. The particle transfer between layers can be interpreted
      as transverse motion of a diffusive nature. The diffusion coefficient associated
      with each layer increases linearly with the layer height. (ii) In polydisperse
      flows consisting of a small percentage (less than 1%) of small disks among large
      ones, the small particles have a net downward motion on which a fluctuating
      behavior is superimposed. At short times, the small particle motion can be
      described as a biased Brownian motion. The ratio of the characteristic time of
      diffusion to that of convection is found to increase with the layer height,
      indicating that the segregation process is more efficient in the upper layers of
      the flow. At longer times, the transverse motion of the small particles seems to
      differ greatly from a classical biased Brownian motion.

PMID- 14682795
TI  - Dynamics of colloidal glass-forming mixtures.
AB  - Recent experimental results from dynamic light scattering on two-component
      colloidal mixtures close to the glass transition are compared to theory. In the
      framework of the mode-coupling theory of the glass transition, close agreement is
      found in general. Discrepancies are identified for the minority-particle
      correlation function, and possible reasons for them are discussed.

PMID- 14682796
TI  - Mesoscopic stability and sedimentation waves in settling periodic arrays.
AB  - The stability of a periodic array of particles settling in a viscous
      incompressible fluid under the influence of gravity is investigated in the
      framework of the point sedimentation model. The simple cubic array is unstable,
      but the body-centered and face-centered cubic arrays with gravity directed along
      one of the crystal axes are mesoscopically stable, i.e., they are stable except
      for very long wavelength in a certain domain of directions of the wave vector. In
      such mesoscopically stable arrays the instability is suppressed in periodic
      boundary conditions for systems smaller than a maximum size. In a stable finite
      system the particles perform small motions about the positions of the regular
      array, and sedimentation waves propagate through the system.

PMID- 14682797
TI  - Crystallization and chain formation in liquid drops.
AB  - Colloidal crystals are easily formed in liquid drops and thin films upon
      evaporation. In this study we use spherical paramagnetic beads, which make it
      possible to manipulate them by an external magnetic field. We show that the
      hydrophilic beads position themselves at a distance from the contact line so that
      they barely touch the water-air interface. Upon applying a magnetic field, the
      magnetic beads can either arrange themselves in a two-dimensional repulsive
      lattice or form attractive vertical chains, depending on the contact angle of the
      drop. We also demonstrate that the vertical chains' position from the contact
      line is quantized and depends on the number of beads in the chain.

PMID- 14682798
TI  - Periodic oscillation of a colloidal disk near a wall in an optical trap.
AB  - Colloidal disks can be stably trapped using optical tweezers. However, when the
      tweezers press the disk against an opposing wall, we observe an instability
      leading to periodic motion which we model using coupled nonlinear equations. The
      resulting "switchback" oscillation involves combined orientational and
      translational motion of the disk. This observation reveals a new degree of
      freedom in colloidal architectures, that is, the ability to drive translational
      motion from a static light field energy source.

PMID- 14682799
TI  - Noise of microstructural environments in late-stage phase coarsening.
AB  - Multiparticle diffusion equations were modeled to simulate the dynamics of late
      stage phase coarsening in the region of lower volume fractions. Local
      environmental information and particle interactions within each coarsening
      "locale" are included in our simulations. These studies reveal that locale
      fluctuations occur in the growth rates of particles due to their differing
      environments. Multiplicative noise provides a sound basis to describe locale
      fluctuation in late-stage coarsening. A Fokker-Planck equation for the particle
      size distribution and its asymptotic solution are obtained.

PMID- 14682800
TI  - Nonlinear voltage profiles and violation of local electroneutrality in ordinary
      surface reactions.
AB  - It is normally assumed that ordinary surface reactions, which involve no charge
      transfer between the surface and electrolyte, have no effect on voltage. The
      present work shows, on the contrary, that nontrivial voltage profiles can be
      produced by ordinary surface reactions. Poisson's equation then implies a nonzero
      bulk charge density, so that local electroneutrality is violated. The specific
      system considered is a planar lead-acid cell, but the results apply more
      generally, so long as the electrolyte charge-carrier diffusivities are not all
      the same. For slow steady reactions the carrier fluxes vary linearly across the
      cell, which produce linearly varying electric field and density gradients. As a
      consequence the voltage profile varies quadratically, and the volume charge
      density is nonzero and uniform. This result has broad implications (e.g., to
      steady-state oxygen loading of high T(c) materials) and may provide a
      contributing mechanism for the origin of the electric fields observed during
      biological growth.

PMID- 14682801
TI  - Shear banding in a lyotropic lamellar phase. I. Time-averaged velocity profiles.
AB  - Using velocity profile measurements based on dynamic light scattering and coupled
      to structural and rheological measurements in a Couette cell, we present
      evidences for a shear banding scenario in the shear flow of the onion texture of
      a lyotropic lamellar phase. Time-averaged measurements clearly show the presence
      of structural shear banding in the vicinity of a shear-induced transition,
      associated with the nucleation and growth of a highly sheared band in the flow.
      Our experiments also reveal the presence of slip at the walls of the Couette
      cell. Using a simple mechanical approach, we demonstrate that our data confirm
      the classical assumption of the shear banding picture, in which the interface
      between bands lies at a given stress sigma(*). We also outline the presence of
      large temporal fluctuations of the flow field, which are the subject of the
      second part of this paper [Salmon et al., Phys. Rev. E 68, 051504 (2003)].

PMID- 14682802
TI  - Shear banding in a lyotropic lamellar phase. II. Temporal fluctuations.
AB  - We analyze the temporal fluctuations of the flow field associated with a shear
      induced transition in a lyotropic lamellar phase: the layering transition of the
      onion texture. In the first part of this work [Salmon et al., Phys. Rev. E 68,
      051503 (2003)], we have evidenced banded flows at the onset of this shear-induced
      transition which are well accounted for by the classical picture of shear
      banding. In the present paper, we focus on the temporal fluctuations of the flow
      field recorded in the coexistence domain. These striking dynamics are very slow
      (100-1000 s) and cannot be due to external mechanical noise. Using velocimetry
      coupled to structural measurements, we show that these fluctuations are due to a
      motion of the interface separating the two differently sheared bands. Such a
      motion seems to be governed by the fluctuations of sigma(*), the local stress at
      the interface between the two bands. Our results thus provide more evidence for
      the relevance of the classical mechanical approach of shear banding even if the
      mechanism leading to the fluctuations of sigma(*) remains unclear.

PMID- 14682803
TI  - Diffusive intertwining of two fluid phases in chemically patterned microchannels.
AB  - Via a coarse-grained model, we simulate the flow of a pressure driven binary AB
      fluid through a three-dimensional microchannel, which is decorated on both top
      and bottom with distinct A- and B-like patches. The advection is "frustrated"
      because A-like patches are placed in the path of the B stream and similarly, B
      like patches are placed in the path of the A fluid. A competition between two
      factors, the advection caused by the imposed flow and the interactions between
      the confined fluids and the patterned substrates, introduces nonlinearity into
      the system. This nonlinear behavior gives rise to a temporally periodic state,
      where the A and B fluids are intertwined. In effect, the simple pattern of
      chemically distinct patches introduces positive feedback, which is responsible
      for the instability of the interface separating the injected fluids.

PMID- 14682804
TI  - Symbiosis of different-sized drops.
AB  - We demonstrate that the usual situation of coarsening in crystal growth or
      Ostwald ripening in evaporating liquid drops is not universal, and when the drops
      coexist with a microscopically thin continuous surface film, a different behavior
      is observed. The predicted behavior was investigated experimentally and supported
      by numerical simulations.

PMID- 14682805
TI  - Growth of the transient planar state in cholesteric liquid crystals.
AB  - Growth and propagation of the transient planar state in the transition of
      cholesteric liquid crystals from the homeotropic to the planar state was
      investigated by both experiments and numerical simulations for planar boundary
      conditions. Interference fringes observed in the measured reflection spectra
      during the evolution of the transient planar state have not been reported in the
      previous study. These interference fringes caused by a Fabry-Perot
      interferometric structure formed in the cell show that the transient planar state
      grows from the surfaces and propagates toward the bulk region in the planar
      sample. Our experimental results for the growth of transient planar state in
      planar boundary conditions are consistent with the previously reported simulation
      studies.

PMID- 14682806
TI  - Forces between elongated particles in a nematic colloid.
AB  - Using molecular dynamics simulations we study the interactions between elongated
      colloidal particles (length to breath ratio >>1) in a nematic host. The
      simulation results are compared to the results of a Landau-de Gennes elastic free
      energy. We find that depletion forces dominate for the sizes of the colloidal
      particles studied. The tangential component of the force, however, allows us to
      resolve the elastic contribution to the total interaction. We find that this
      contribution differs from the quadrupolar interaction predicted at large
      separations. The difference is due to the presence of nonlinear effects, namely,
      the change in the positions and structure of the defects and their annihilation
      at small separations.

PMID- 14682807
TI  - Theoretical model for the discrete flexoelectric effect and a description for the
      sequence of intermediate smectic phases with increasing periodicity.
AB  - A general phenomenological description and a simple molecular model is proposed
      for the "discrete" flexoelectric effect in tilted smectic liquid crystal phases.
      This effect defines a polarization in a smectic layer induced by a difference of
      director orientations in the two smectic layers adjacent to it. It is shown that
      the "discrete" flexoelectric effect is determined by electrostatic dipole
      quadrupole interaction between positionally correlated molecules located in
      adjacent smectic layers, while the corresponding dipole-dipole interaction is
      responsible for a coupling between polarization vectors in neighboring layers. It
      is shown that a simple phenomenological model of a ferrielectric smectic liquid
      crystal, which has recently been proposed in the literature, can be used to
      describe the whole sequence of intermediate chiral smectic C* phases with
      increasing periods, and to determine the nonplanar structure of each phase
      without additional assumptions. In this sequence the phases with three- and four
      layer periodicities have the same structure, as observed in the experiment. The
      theory predicts also the structure of intermediate phases with longer periods
      that have not been studied experimentally so far. The structures of intermediate
      phases with periodicities of up to nine layers are presented together with the
      phase diagrams, and a relationship between molecular chirality and the three
      dimensional structure of intermediate phases is discussed. It is considered also
      how the coupling between the spontaneous polarization determined by molecular
      chirality and the induced polarization determined by the discrete flexoelectric
      effect stabilizes the nonplanar structure of intermediate phases.

PMID- 14682808
TI  - Theory of layer structure in ferroelectric liquid crystal devices in applied
      electric fields.
AB  - We propose a model for the free energy of a ferroelectric liquid crystal formed
      by cooling a sample from the smectic-A phase between parallel substrates. Under
      these circumstances the smectic layers may deform into V-shaped structures known
      as chevrons. Application of a strong electric field causes the layers to return
      to a flat shape, but this can occur in a number of ways. In the model presented
      here, it is a parameter related to the layer compression modulus that is the
      principal factor in determining the nature of the field-induced transition from
      chevrons to flat layers. When this parameter is large, the transition is sudden,
      but when it is small the chevron first takes on a rounded form before flattening.
      At intermediate values the tip of the chevron first flattens, and then this flat
      region gradually grows to encompass the entire layer.

PMID- 14682809
TI  - Critical behavior of thermal parameters at the smectic-A-hexatic-B and smectic-A
      smectic-C phase transitions in liquid crystals.
AB  - High temperature resolution measurements of thermal conductivity, thermal
      diffusivity, and specific heat, with simultaneous polarized light visual
      inspection of the sample, have been performed at two different liquid crystal
      phase transitions: the SmA-SmC (Smectic-A-Smectic-C) and the SmA-HexB (Smectic-A
      hexatic-B) in racemic A7 [4-(3-methyl-2-chlorobutanoyloxy)-4(')
      heptyloxybiphenyl] and 65OBC (n-hexyl-4(')-n-pentyloxybiphenyl-4-carboxylate)
      compounds, respectively. In the past, anomalies in the thermal conductivity at
      the transitions have been reported. Our results indicate a nonsingular behavior
      of the thermal conductivity at both transitions, similarly to what has been
      previously reported for the smectic-A-nematic phase transition. It is also shown
      how, in several cases, the nature of the transition can be affected by the sample
      thermal history due to the presence of strain annealing phenomena.

PMID- 14682810
TI  - Proposal for the temperature-electric-field phase diagram of a ferroelectric
      smectic-C* liquid crystal.
AB  - We report on the results of extensive optical measurements on the ferroelectric
      smectic-C* phase of the chiral liquid crystal 4-(2(') methyl butyl) phenyl 4(')-n
      octylbiphenyl-4-carboxylate. We have explored the entire temperature-electric
      field phase space searching for all possible phase transitions in the C* region
      and have characterized them both as to their character, including whether they
      are first or second order, and also whether they are of instability or nucleation
      type. Our results lead us to conclude that the experimental phase diagram is
      incompatible with all existing theoretical models for the C* phase transitions.
      We propose instead a phase diagram where two second-order lines and one first
      order line meet at a triple point that we tentatively identify as a Lifshitz
      point.

PMID- 14682811
TI  - Self-avoiding linear and star polymers anchored to membranes.
AB  - The effect of anchored linear and star polymers in the mushroom regime on the
      curvature elasticity of membranes is investigated by Monte Carlo simulations and
      scaling arguments. We describe a simulation method to calculate the free energy
      of anchored polymers as a function of membrane curvature, which is accurate
      enough to extract reliable values for the polymer-induced spontaneous curvature
      Deltac(0), bending rigidity Deltakappa, and saddle-splay modulus Deltakappa;. For
      self-avoiding linear and star polymers, the universal amplitudes of the curvature
      moduli as well as the effects of finite chain lengths are determined, to our
      knowledge, for the first time. We find that star polymers have the unique
      property of strongly affecting c(0) and kappa, but leaving kappa; essentially
      unchanged. Furthermore, star polymers are shown to have a much stronger effect on
      membrane properties than an equivalent number of linear polymers.

PMID- 14682812
TI  - Quenched and annealed disorder in randomly grafted copolymer melts.
AB  - A model of randomly grafted AB copolymer melts is constructed in which flexible B
      polymer grafts are statistically attached at three possible sites along flexible
      A polymer backbones. An incompressible melt of such molecules is examined
      theoretically at equilibrium for two situations: (1) the grafting is irreversible
      so that the chemical disorder associated with the statistical placement of the
      grafts is quenched, and (2) the grafting is reversible so that the disorder is
      annealed. Because of the simplicity of the model, we are able to exactly carry
      out the two types of disorder averages, yielding effective field theories for the
      quenched and annealed cases. These field theories are investigated in the mean
      field approximation, but without further invoking the usual weak-amplitude random
      phase approximation. Our results clarify the conditions for which quenched and
      annealed averages can be interchanged.

PMID- 14682813
TI  - Power laws in polymer solution dynamics.
AB  - The dynamical screening length xi(h) in semidilute to highly concentrated polymer
      solutions of poly(methyl methacrylate) in propylene carbonate has been examined
      using photon correlation spectroscopy and pulsed field gradient nuclear magnetic
      resonance. A crossover between different concentration dependent regimes, xi(h)
      approximately phi(-alpha), where alpha is found to be approximately 0.5,
      approximately 1, and approximately 2, is observed when the local viscosity is
      taken into account. Here phi is the volume fraction of polymer in the solution.
      Well-defined crossovers between alpha=0.5 and alpha=1 corresponding to a
      transition from a marginal solvent to a theta solvent behavior have been
      predicted to occur due to the reduction of excluded-volume effects between the
      spatially correlated polymer segments with increasing polymer volume fraction.
      However, a clear experimental validation of the crossover has never been
      presented before. The third regime (alpha approximately 2) is observed in the
      highly concentrated region where the static screening length is comparable to the
      persistence length of the polymer. The observation indicates that the rigid rod
      model previously used to describe concentrated solutions is an oversimplification
      valid only in the very high concentration limit. The obtained results at high
      concentrations are discussed in the frame of a simple physical model where
      segments at the persistence length scale are treated as flexible rodlike
      segments.

PMID- 14682814
TI  - Kinetics of the coil-to-helix transition on a rough energy landscape.
AB  - The kinetics of folding of a fully atomic seven-residue polyalanine peptide in an
      implicit solvent are studied using molecular dynamics simulations. The use of an
      implicit solvent is found to dramatically increase the frustration of the energy
      landscape relative to simulations performed in an explicit solvent [Phys. Rev.
      Lett. 85, 2637 (2000)]. While the native state in both implicit and explicit
      solvent simulations is an alpha-helix, the kinetics of the coil-to-helix
      transition differ significantly. In contrast to the explicit solvent simulations,
      the native state in the implicit solvent simulations is not kinetically
      accessible at temperatures where it is thermodynamically stable and could not be
      brought into equilibrium with other conformational states. At temperatures where
      statistical equilibrium was achieved, the conformational diffusion folding
      mechanism, found earlier to be adequate for this peptide in an explicit solvent
      [Phys. Rev. Lett. 85, 2637 (2000)], is met with only limited success. Issues
      relating to the evaluation of the quality of implicit solvent models on the basis
      of thermodynamic criteria only are reexamined.

PMID- 14682815
TI  - Cohesive energy, stability, and structural transitions in polyelectrolyte
      bundles.
AB  - A lattice of uniformly charged, infinitesimally thin rods decorated with an
      ordered array of counterions exhibits anomalous behavior as the spacing between
      the rods is varied. In particular, the counterion lattice undergoes a sequence of
      structural shearing or "tilting," phase transformations as the spacing between
      the rods decreases. The potential implications of this behavior with respect to
      the packaging of biologically relevant polyelectrolytic molecules are commented
      upon.

PMID- 14682816
TI  - Stability and bifurcation in an integral-delay model of cardiac reentry including
      spatial coupling in repolarization.
AB  - We present the bifurcation analysis of a revised version of the integral-delay
      model [Courtemanche et al., Siam J. Appl. Math. 56, 119 (1996)] of reentry in a
      one-dimensional ring that includes a spatial coupling in the calculation of the
      action potential duration. This coupling is meant to reproduce the modulation of
      repolarization by the diffusive current flowing through the intercellular
      resistance. We show that coupling modifies the criterion for the stability of the
      period-1 solution, which is no longer uniquely related to the action potential
      restitution curve, but depends also on the degree of coupling between cells and
      on the dispersion relation of the velocity. Coupling also changes the scenario
      from an infinite-dimension Hopf bifurcation to a finite sequence of Hopf
      bifurcations that take place at different ring lengths.

PMID- 14682817
TI  - Statistical mechanics of RNA folding: a lattice approach.
AB  - We propose a lattice model for the secondary structure of RNA based on a self
      interacting two-tolerant trail. Self-avoidance and pseudoknots are taken into
      account. We investigate a simple version of the model in which the native state
      of RNA consists of just one hairpin. Using exact arguments and Monte Carlo
      simulations we determine the phase diagram for this case. We show that the
      denaturation transition is first order and can either occur directly or through
      an intermediate molten phase.

PMID- 14682818
TI  - Theoretical ellipsoidal model of gastric electrical control activity propagation.
AB  - A theoretical model of electric current propagation in the human stomach is
      developed using an approach in which the shape of the organ is assumed to be a
      truncated ellipsoid whose dimensions can be determined from anatomic
      measurements. The gastric electrical activity is simulated using a ring of
      isopotential electric current dipoles that are generated by a pacemaker situated
      in the gastric corpus. The dipoles propagate in the direction of the pylorus at a
      frequency of three cycles per minute. The advantages of employing ellipsoids in
      the analytical formulation of this gastric model are discussed in addition to the
      realism and usefulness of the approach.

PMID- 14682819
TI  - Drug-induced modification of the system properties associated with spontaneous
      human electroencephalographic activity.
AB  - The benzodiazepine (BZ) class of minor tranquilizers are important modulators of
      the gamma-amino butyric acid (GABA(A))/BZ receptor complex that are well known to
      affect the spectral properties of spontaneous electroencephalographic activity.
      While it is experimentally well established that the BZs reduce total alpha band
      (8-13 Hz) power and increase total beta band (13-30 Hz) power, it is unclear what
      the physiological basis for this effect is. Based on a detailed theory of
      cortical electrorhythmogenesis it is conjectured that such an effect is
      explicable in terms of the modulation of GABAergic neurotransmission within
      locally connected populations of excitatory and inhibitory cortical neurons.
      Motivated by this theory, fixed order autoregressive moving average (ARMA) models
      were fitted to spontaneous eyes-closed electroencephalograms recorded from
      subjects before and approximately 2 h after the oral administration of a single 1
      mg dose of the BZ alprazolam. Subsequent pole-zero analysis revealed that BZs
      significantly transform the dominant system pole such that its frequency and
      damping increase. Comparisons of ARMA derived power spectra with fast Fourier
      transform derived spectra indicate an enhanced ability to identify benzodiazepine
      induced electroencephalographic changes. This experimental result is in accord
      with the theoretical predictions implying that alprazolam enhances inhibition
      acting on inhibitory neurons more than inhibition acting on excitatory neurons.
      Further such a result is consistent with reported cortical neuronal distributions
      of the various GABA(A) receptor pharmacological subtypes. Therefore
      physiologically specified fixed order ARMA modeling is expected to become an
      important tool for the systematic investigation and modeling of a wide range of
      cortically acting compounds.

PMID- 14682820
TI  - Particle transport in asymmetric scanning-line optical tweezers.
AB  - We describe a scanning-line optical tweezing technique with an asymmetric beam
      profile in the back focal plane of the microscope objective. The motion of a
      trapped particle along the scan line is studied as a function of beam asymmetry,
      and it is shown that this technique can be used to exert a constant lateral force
      on the particle, realizing purely optical constant-force tweezing. The observed
      effect is attributed in a geometric optics model to a non-zero lateral component
      of the scattering force.

PMID- 14682821
TI  - Electronic structures of Ascaris trypsin inhibitor in solution.
AB  - The electronic structures of Ascaris trypsin inhibitor in solution are obtained
      by the first-principles, all-electron, ab initio calculation using the self
      consistent cluster-embedding (SCCE) method. The inhibitor, made up of 62 amino
      acid residues with 912 atoms, has two three-dimensional solution structures: 1ata
      and 1atb. The calculated ground-state energy of structure 1atb is lower than that
      of structure 1ata by 6.12 eV. The active sites are determined and explained: only
      structure 1atb has a N terminal at residue ARG+31. This shows that the structure
      1atb is the stable and active form of the inhibitor, which is in agreement with
      the experimental results. The calculation reveals that some parts of the
      inhibitor can be easily changed while the inhibitor's biological activity may be
      kept. This kind of information may be helpful in fighting viruses such as AIDS,
      SARS, and flu, since these viruses have higher variability. The calculation
      offers an independent theoretical estimate of the precision of structure
      determination.

PMID- 14682822
TI  - Global stability of neural networks with distributed delays.
AB  - In this paper, a model describing the dynamics of recurrent neural networks with
      distributed delays is considered. Some sufficient criteria are derived ensuring
      the global asymptotic stability of distributed-delay recurrent neural networks
      with more general signal propagation functions by introducing real parameters
      p>1, q(ij)>0, and r(jj)>0, i,j=1, em leader,n, and applying the properties of the
      M matrix and inequality techniques. We do not assume that the signal propagation
      functions satisfy the Lipschitz condition and do not require them to be bounded,
      differentiable, or strictly increasing. Moreover, the symmetry of the connection
      matrix is also not necessary. These criteria are independent of the delays and
      possess infinitely adjustable real parameters, which is important in signal
      processing, especially in moving image treatment and the design of networks.

PMID- 14682824
TI  - Characterization of the order-disorder transition of a charged hard-sphere model.
AB  - Monte Carlo simulations at constant pressure are used to characterize the
      structure of the restricted primitive model in the tetragonal-ordered solid
      phase. A method to estimate the location of the order-disorder transition and the
      densities of the coexistence phases is discussed. The results support the weakly
      first-order character of the transition.

PMID- 14682823
TI  - Virus shapes and buckling transitions in spherical shells.
AB  - We show that the icosahedral packings of protein capsomeres proposed by Caspar
      and Klug for spherical viruses become unstable to faceting for sufficiently large
      virus size, in analogy with the buckling instability of disclinations in two
      dimensional crystals. Our model, based on the nonlinear physics of thin elastic
      shells, produces excellent one-parameter fits in real space to the full three
      dimensional shape of large spherical viruses. The faceted shape depends only on
      the dimensionless Foppl-von Karman number gamma=YR(2)/kappa, where Y is the two
      dimensional Young's modulus of the protein shell, kappa is its bending rigidity,
      and R is the mean virus radius. The shape can be parametrized more quantitatively
      in terms of a spherical harmonic expansion. We also investigate elastic shell
      theory for extremely large gamma, 10(3)<gamma<10(8), and find results applicable
      to icosahedral shapes of large vesicles studied with freeze fracture and electron
      microscopy.

PMID- 14682825
TI  - How closely can a solid approach an air-water surface without becoming wet?
AB  - Through a study of the van der Waals interaction between a solid and an air-water
      interface, we investigate the practical and fundamental problem of the limiting
      height at which an object can approach a free surface. A numerical study of the
      interface shape reveals dependencies governed by two disparate length scales
      associated with the relative strengths of the van der Waals and bouyancy forces,
      to surface tension. A study of the limits of solvability of the governing
      equation has led to the principal result: a closed-form expression for the
      absolute limiting height to which an object can be lowered to the air-water
      interface. The formula depends explicitly and only on the Hamaker constant of the
      van der Waals force and the geometry of the solid.

PMID- 14682826
TI  - Stable and unstable surface evolution during the drying of a polymer solution
      drop.
AB  - Drying of a sessile drop of a complex liquid can lead to intriguing complex
      shapes. We report here a study dealing with a model system, made of a
      hydrosoluble polymer that is glassy when pure. Under solvent evaporation,
      polymers accumulate near the vapor/drop interface and may form a glassy skin,
      which bends as the volume of liquid it encloses decreases. The conditions for the
      occurrence of this buckling instability have been investigated; the experimental
      results are well explained by a model that compares the characteristic times for
      drying and for the formation of a glassy skin. Depending on the experimental
      conditions, different types of shape distortion take place; secondary
      instabilities that break the axisymmetry are also observed.

PMID- 14682827
TI  - Stability of a neural network model with small-world connections.
AB  - Small-world networks are highly clustered networks with small distances among the
      nodes. There are many biological neural networks that present this kind of
      connection. There are no special weightings in the connections of most existing
      small-world network models. However, this kind of simply connected model cannot
      characterize biological neural networks, in which there are different weights in
      synaptic connections. In this paper, we present a neural network model with
      weighted small-world connections and further investigate the stability of this
      model.

PMID- 14682828
TI  - Comment on "Restricted curvature model with suppression of extremal height".
AB  - Recently Jeong and Kim [Phys. Rev. E 66, 051605 (2002)] investigated the scaling
      properties of equilibrium self-flattening surfaces subject to a restricted
      curvature constraint. In one dimension (1D), they found numerically that the
      stationary roughness exponent alpha approximately 0.561 and the window exponent
      delta approximately 0.423. We present an analytic argument for general self
      flattening surfaces in D dimensions, leading to alpha=Dalpha(0)/(D+alpha(0)) and
      delta=D/(D+alpha(0)), where alpha(0) is the roughness exponent for equilibrium
      surfaces without the self-flattening mechanism. In case of surfaces subject to a
      restricted curvature constraint, it is known exactly that alpha(0)=3/2 in 1D,
      which leads to alpha=3/5 and delta=2/5. Small discrepancies between our analytic
      values and their numerical values may be attributed to finite size effects.

PMID- 14682830
TI  - Elasticity of randomly diluted central force networks under tension.
AB  - We study the rigidity of two-dimensional site-diluted central force triangular
      networks under tension. We calculate the shear modulus micro directly and fit it
      with a power law of the form mu approximately (p-p*)(f), where p is the
      concentration of sites, p* its critical value, and f the critical exponent. We
      find that the critical behavior of mu is quite sensitive to tension. As the
      tension is increased there is at first a sharp drop in the values of both p* and
      f, followed by a slower decrease towards the values of the diluted Gaussian
      spring network (or random resistor network). We find that the size of the
      critical region is also sensitive to tension. The tension-free system has a
      narrower critical regime with the power law failing for p>0.8. In contrast, a
      small tension is sufficient to extend the power law to near p=1. The physical
      basis for these behaviors is discussed.

PMID- 14682831
TI  - Effective dimensions and percolation in hierarchically structured scale-free
      networks.
AB  - We introduce appropriate definitions of dimensions in order to characterize the
      fractal properties of complex networks. We compute these dimensions in a
      hierarchically structured network of particular interest. In spite of the
      nontrivial character of this network that displays scale-free connectivity among
      other features, it turns out to be approximately one dimensional. The dimensional
      characterization is in agreement with the results on statistics of site
      percolation and other dynamical processes implemented on such a network.

PMID- 14682832
TI  - Oscillator death on small-world networks.
AB  - We have investigated the oscillator death behavior on small-world networks. On
      one hand, we find that small-world connectivity can eliminate the oscillator
      death present in the regular lattice. On the other hand, the small-world
      connectivity can also lead to global oscillator death which is absent in the
      regular lattice or the completely random network.

PMID- 14682833
TI  - Stable equilibrium based on Levy statistics: Stochastic collision models
      approach.
AB  - We investigate equilibrium properties of two very different stochastic collision
      models: (i) the Rayleigh particle and (ii) the driven Maxwell gas. For both
      models the equilibrium velocity distribution is a Levy distribution, the Maxwell
      distribution being a special case. We show how these models are related to
      fractional kinetic equations. Our work demonstrates that a stable power-law
      equilibrium, which is independent of details of the underlying models, is a
      natural generalization of Maxwell's velocity distribution.

PMID- 14682834
TI  - Explicit analytical solution for scaling quantum graphs.
AB  - We show that scaling quantum graphs with arbitrary topology are explicitly
      analytically solvable. This is surprising since quantum graphs are excellent
      models of quantum chaos and quantum chaotic systems are not usually explicitly
      analytically solvable.

PMID- 14682835
TI  - Density fingering of an exothermic autocatalytic reaction.
AB  - Density fingering of exothermic autocatalytic fronts in vertically oriented
      porous media and Hele-Shaw cells is studied theoretically for chemical reactions
      where the solutal and thermal contribution to density changes have opposite
      signs. The competition between these two effects leads to thermal plumes for
      ascending fronts. The descending fronts behave strikingly differently as they can
      feature, for some values of the parameters, fingers of constant amplitude and
      wavelength. The differences between up and down going fronts are discussed in
      terms of dispersion curves and nonlinear dynamics. The theoretically predicted
      dispersion curves are experimentally evidenced with the chlorite-tetrathionate
      reaction.

PMID- 14682836
TI  - Improved epsilon expansion for three-dimensional turbulence: summation of nearest
      dimensional singularities.
AB  - An improved epsilon expansion in the d-dimensional (d>2) stochastic theory of
      turbulence is constructed by taking into account pole singularities at d-->2 in
      coefficients of the epsilon expansion of universal quantities. Effectiveness of
      the method is illustrated by a two-loop calculation of the Kolmogorov constant in
      three dimensions.

PMID- 14682837
TI  - Solitonic lattices in photorefractive crystals.
AB  - Two-dimensional spatial solitonic lattices are generated and investigated
      experimentally and numerically in a Sr(x)Ba(1-x)Nb(2)O(6):Ce crystal. An enhanced
      stability of these lattices is achieved by exploiting the anisotropy of coherent
      soliton interaction, in particular the relative phase between soliton rows. The
      manipulation of individual soliton channels is achieved by the use of
      supplementary control beams.

PMID- 14682838
TI  - Efficient mixed-force first-principles molecular dynamics.
AB  - We present an efficient method to mix well converged ab initio forces with
      simpler and faster ones in molecular dynamics. While the cheap forces are
      evaluated every time step, the converged ones correct the trajectory only every n
      time steps. For convenience, both types of forces are calculated with the same
      basic scheme, using density functional theory, norm-conserving pseudopotentials,
      and a basis set of numerical atomic orbitals. The cheap forces are evaluated with
      a short-range minimal basis set and the non-self-consistent Harris functional.
      Since these evaluations are hundreds of times faster than those of the converged
      forces, they add a negligible cost, and the boost in computational efficiency is
      approximately a factor n. Our results indicate that one can use values of n of up
      to 10, without affecting significantly the calculated structural and dynamical
      magnitudes.

PMID- 14682839
TI  - Strouhal-Reynolds number relationship for bluff-body flows numerically simulated
      by an artificial boundary method.
AB  - The incidence of the numerical resolution and the blockage effect are
      investigated in an embedding method for solving bidimensional bluff body flows.
      This method consists of using an artificial boundary instead of imposing exact
      conditions on the body surface. It requires us to define a blur frontier ratio
      and a blockage effect ratio. The blockage effect ratio is found using the mean
      flow of a circular cylinder directly. The blur frontier ratio is obtained by
      comparison of the present method with another numerical method where explicit
      boundary conditions on the body are imposed. For this ratio, the investigations
      are based on the flow past a square cylinder which discard the uncertainty on the
      surface of the body for the embedding method. Hence, the two factors allow the
      transformations of the Strouhal and the Reynolds numbers for the flow past a
      circular cylinder. The universal Strouhal-Reynolds number relationship of the
      circular cylinder is finally recovered.

PMID- 14682840
TI  - Winding angle variance of Fortuin-Kasteleyn contours.
AB  - The variance in the winding number of various random fractal curves, including
      the self-avoiding walk, the loop-erased random walk, contours of Fortuin-Kastelyn
      clusters, and stochastic Loewner evolution, has been studied by numerous
      researchers. Usually the focus has been on the winding at the end points. We
      measure the variance in winding number at typical points along the curve. More
      generally, we study the winding at points where k strands come together, and some
      adjacent strands may be conditioned not to hit each other. The measured values
      are consistent with an interesting conjecture.

PMID- 14682841
TI  - Universal finite-size scaling behavior and universal dynamical scaling behavior
      of absorbing phase transitions with a conserved field.
AB  - We analyze numerically three different models exhibiting an absorbing phase
      transition. We focus on the finite-size scaling as well as the dynamical scaling
      behavior. An accurate determination of several critical exponents allows one to
      validate certain hyperscaling relations. Using these hyperscaling relations it is
      possible to express the avalanche exponents of a self-organized critical system
      in terms of the ordinary exponents of a continuous absorbing phase transition.

PMID- 14682842
TI  - Simple dynamical models for hierarchical bunching.
AB  - Simple one-dimensional models for hierarchical bunching are proposed. A uniform
      state with equal spacing is linearly unstable and bunching clusters are created.
      The bunching clusters are further merged into even larger clusters. The
      coarsening process towards the larger clusters obeys a power law for the long
      range forces. The exponent of the power law depends on the long-range forces. A
      continuum version of the lattice model with linear repulsive force is studied
      more in detail. The model has a form of a kind of spinodal decomposition. The
      coarsening dynamics is similar to a one-dimensional version of the Ostwald
      ripening.

PMID- 14682843
TI  - Rigidity percolation in a field.
AB  - Rigidity percolation with g degrees of freedom per site is analyzed on randomly
      diluted Erdos-Renyi graphs, with average connectivity gamma, in the presence of a
      field h. In the (gamma,h) plane, the rigid and flexible phases are separated by a
      line of first-order transitions whose location is determined exactly. This line
      ends at a critical point with classical critical exponents. Analytic expressions
      are given for the densities n(F) of uncanceled degrees of freedom and gamma(r) of
      redundant bonds. Upon crossing the coexistence line, gamma(r) and n(F) are
      continuous, although their first derivatives are discontinuous. We extend, for
      the case of nonzero field, a recently proposed hypothesis, namely, that the
      density of uncanceled degrees of freedom is a "free energy" for rigidity
      percolation. Analytic expressions are obtained for the energy, entropy, and
      specific heat. Some analogies with a liquid-vapor transition are discussed.
      Particularizing to zero field, we find that the existence of a (g+1) core is a
      necessary condition for rigidity percolation with g degrees of freedom. At the
      transition point gamma(c), Maxwell counting of degrees of freedom is exact on the
      rigid cluster and on the (g+1) rigid core, i.e., the average coordination of
      these subgraphs is exactly 2g, although gamma(c), the average coordination of the
      whole system, is smaller than 2g. gamma(c) is found to converge to 2g for large
      g, i.e., in this limit Maxwell counting is exact globally as well.

PMID- 14682844
TI  - Scaling properties of random walks on small-world networks.
AB  - Using both numerical simulations and scaling arguments, we study the behavior of
      a random walker on a one-dimensional small-world network. For the properties we
      study, we find that the random walk obeys a characteristic scaling form. These
      properties include the average number of distinct sites visited by the random
      walker, the mean-square displacement of the walker, and the distribution of first
      return times. The scaling form has three characteristic time regimes. At short
      times, the walker does not see the small-world shortcuts and effectively probes
      an ordinary Euclidean network in d dimensions. At intermediate times, the
      properties of the walker shows scaling behavior characteristic of an infinite
      small-world network. Finally, at long times, the finite size of the network
      becomes important, and many of the properties of the walker saturate. We propose
      general analytical forms for the scaling properties in all three regimes, and
      show that these analytical forms are consistent with our numerical simulations.

PMID- 14682845
TI  - Multispecies annihilating random walk transition at zero branching rate: cluster
      scaling behavior in a spin model.
AB  - Numerical and theoretical studies of a one-dimensional spin model with locally
      broken spin symmetry are presented. The multispecies annihilating random walk
      transition found at zero branching rate previously is investigated now concerning
      the cluster behavior of the underlying spins. Generic power-law behaviors are
      found, besides the phase transition point, also in the active phase with
      fulfillment of the hyperscaling law. On the other hand scaling laws connecting
      bulk and cluster exponents are broken--a possibility in no contradiction with
      basic scaling assumptions because of the missing absorbing phase.

PMID- 14682846
TI  - Network bipartivity.
AB  - Systems with two types of agents with a preference for heterophilous interaction
      produce networks that are more or less close to bipartite. We propose two
      measures quantifying the notion of bipartivity. The two measures-one well known
      and natural, but computationally intractable, and the other computationally less
      complex, but also less intuitive-are examined on model networks that continuously
      interpolate between bipartite graphs and graphs with many odd circuits. We find
      that the bipartivity measures increase as we tune the control parameters of the
      test networks to intuitively increase the bipartivity, and thus conclude that the
      measures are quite relevant. We also measure and discuss the values of our
      bipartivity measures for empirical social networks (constructed from professional
      collaborations, Internet communities, and field surveys). Here we find, as
      expected, that networks arising from romantic online interaction have high, and
      professional collaboration networks have low, bipartivity values. In some other
      cases, probably due to low average degree of the network, the bipartivity
      measures cannot distinguish between romantic and friendship oriented interaction.

PMID- 14682847
TI  - Nonuniversality and scaling breakdown in a nonconservative earthquake model.
AB  - We use extensive numerical simulations to test recent claims of universality in
      the nonconservative regime of the Olami-Feder-Christensen model. By studying
      larger systems and a wider range of dissipation levels than previously considered
      we conclude that there is no evidence of universality in the model with only
      limited regions of the event size distributions displaying power-law behavior. We
      further analyze the dimension of the largest events in the model, D(max), using a
      multiscaling method. This reveals that although D(max) initially increases with
      system size, for larger systems the dimension ultimately decreases with system
      size casting further doubt on the criticality of the model.

PMID- 14682848
TI  - Rational-driver approximation in car-following theory.
AB  - The problem of a car following a lead car driven with constant velocity is
      considered. To derive the governing equations for the following car dynamics a
      cost functional is constructed. This functional ranks the outcomes of different
      driving strategies, which applies to fairly general properties of the driver
      behavior. Assuming rational-driver behavior, the existence of the Nash
      equilibrium is proved. Rational driving is defined by supposing that a driver
      corrects continuously the car motion to follow the optimal path minimizing the
      cost functional. The corresponding car-following dynamics is described quite
      generally by a boundary value problem based on the obtained extremal equations.
      Linearization of these equations around the stationary state results in a
      generalization of the widely used optimal velocity model. Under certain
      conditions (the "dense traffic" limit) the rational car dynamics comprises two
      stages, fast and slow. During the fast stage a driver eliminates the velocity
      difference between the cars, the subsequent slow stage optimizes the headway. In
      the dense traffic limit an effective Hamiltonian description is constructed. This
      allows a more detailed nonlinear analysis. Finally, the differences between
      rational and bounded rational driver behavior are discussed. The latter, in
      particular, justifies some basic assumptions used recently by the authors to
      construct a car-following model lying beyond the frameworks of rationality.

PMID- 14682849
TI  - Dynamics of market correlations: taxonomy and portfolio analysis.
AB  - The time dependence of the recently introduced minimum spanning tree description
      of correlations between stocks, called the "asset tree" has been studied in order
      to reflect the financial market taxonomy. The nodes of the tree are identified
      with stocks and the distance between them is a unique function of the
      corresponding element of the correlation matrix. By using the concept of a
      central vertex, chosen as the most strongly connected node of the tree, an
      important characteristic is defined by the mean occupation layer. During crashes,
      due to the strong global correlation in the market, the tree shrinks
      topologically, and this is shown by a low value of the mean occupation layer. The
      tree seems to have a scale-free structure where the scaling exponent of the
      degree distribution is different for "business as usual" and "crash" periods. The
      basic structure of the tree topology is very robust with respect to time. We also
      point out that the diversification aspect of portfolio optimization results in
      the fact that the assets of the classic Markowitz portfolio are always located on
      the outer leaves of the tree. Technical aspects such as the window size
      dependence of the investigated quantities are also discussed.

PMID- 14682850
TI  - Critical adsorption in a well-defined geometry.
AB  - A fluid's density profile near a wall is predicted to assume a universal shape
      near the liquid-vapor critical point, a phenomenon termed critical adsorption.
      This universal shape is predicted to depend on the boundary conditions of the
      fluid at the walls and is predicted to be a function of the ratio z/xi, where z
      is the distance from the wall and xi is the bulk correlation length. A body of
      evidence confirms the analogous phenomenon of critical adsorption in binary
      fluids near the critical demixing point, but in the simple liquid-vapor system
      the experimental situation is not as clear. For example, critical adsorption of
      SF6 was observed in porous glass for reduced temperature t=T/T(c)-1>10(-3).
      However, for t<10(-3) a desorption behavior is seen. This desorption has so far
      resisted rigorous theoretical explanation. We report measurements of the critical
      adsorption of nitrogen inside a capacitor gap with a simple parallel plate
      geometry and open gap of 3 microm. Unlike the previous experiments with SF6, the
      data show a monotonic increase in the adsorption between t=5 x 10(-4) and t=10(
      6), consistent with theoretical prediction and without any indication of
      desorption.

PMID- 14682851
TI  - Equation of state for a partially ionized gas. II.
AB  - The derivation of equations of state for fluid phases of a partially ionized gas
      or plasma is addressed from a fundamental point of view. A spherical cellular
      model is deduced for the hot curve limit (or ideal Fermi gas). Next the Coulomb
      interactions are added to the spherical cellular model for general ionic charge
      Z. Then an independent electron model within a Z electron cell plus several many
      body effects are employed. Numerical examples of the theory for several elements
      (H, Li, N, Na, K, Ni, Rb, Pd, Cs, and Er) are reported. These results reduce in
      various limits of temperature and density to the expected behavior. They display
      electron, localization-delocalization phase transitions of liquid-gas character.
      In the higher Z elements, a second possible critical point has been found. The
      critical pressure, electron density and temperature for the lower-density
      critical points seem to obey power laws as a function of Z.

PMID- 14682852
TI  - Statistical mechanics in the extended Gaussian ensemble.
AB  - The extended Gaussian ensemble (EGE) is introduced as a generalization of the
      canonical ensemble. This ensemble is a further extension of the Gaussian ensemble
      introduced by Hetherington [J. Low Temp. Phys. 66, 145 (1987)]. The statistical
      mechanical formalism is derived both from the analysis of the system attached to
      a finite reservoir and from the maximum statistical entropy principle. The
      probability of each microstate depends on two parameters beta and gamma which
      allow one to fix, independently, the mean energy of the system and the energy
      fluctuations, respectively. We establish the Legendre transform structure for the
      generalized thermodynamic potential and propose a stability criterion. We also
      compare the EGE probability distribution with the q-exponential distribution. As
      an example, an application to a system with few independent spins is presented.

PMID- 14682853
TI  - Structure and transport properties of liquid clusters in a drying porous medium.
AB  - The structure and transport properties of drying water clusters in porous media
      have been studied with a site-bond invasion percolation (IP) model. In this model
      an invader (air) enters a lattice (porous network) filled with defender (water)
      via a sequence of invasion steps. The decision to invade a site (pore) is made on
      the basis of the resistance of the bonds (throats). It is found that the backbone
      of the defender network and its transport properties are the same as in ordinary
      percolation (OP). In particular the strength exponent of the backbone
      beta(B)=0.99+/-0.03, the correlation length exponent nu=0.88, and the
      conductivity exponent mu=1.99+/-0.04 are the same as in OP. The total network
      deviates from networks generated with OP: on short length scales the formation of
      branches is suppressed because pores with many empty neighbors are preferentially
      invaded. The differences between our IP results and the outcomes of OP are a
      consequence of the invasion mechanism. This makes clear that the details of the
      invasion process are important for understanding the transport properties in a
      drying network.

PMID- 14682854
TI  - Universal energy distribution for interfaces in a random-field environment.
AB  - We study the energy distribution function rho(E) for interfaces in a random-field
      environment at zero temperature by summing the leading terms in the perturbation
      expansion of rho(E) in powers of the disorder strength, and by taking into
      account the nonperturbational effects of the disorder using the functional
      renormalization group. We have found that the average and the variance of the
      energy for one-dimensional interface of length L behave as, <E>(R) proportional
      to L ln L, DeltaE(R) proportional to L, while the distribution function of the
      energy tends for large L to the Gumbel distribution of the extreme value
      statistics.

PMID- 14682855
TI  - Statistics of extremal intensities for Gaussian interfaces.
AB  - The extremal Fourier intensities are studied for stationary Edwards-Wilkinson
      type, Gaussian, interfaces with power-law dispersion. We calculate the
      probability distribution of the maximal intensity and find that, generically, it
      does not coincide with the distribution of the integrated power spectrum (i.e.,
      roughness of the surface), nor does it obey any of the known extreme statistics
      limit distributions. The Fisher-Tippett-Gumbel limit distribution is, however,
      recovered in three cases: (i) in the nondispersive (white noise) limit, (ii) for
      high dimensions, and (iii) when only short-wavelength modes are kept. In the last
      two cases the limit distribution emerges in nonconventional scenarios.

PMID- 14682856
TI  - Optimal analysis on the performance of an irreversible harmonic quantum Brayton
      refrigeration cycle.
AB  - An irreversible model of a quantum refrigeration cycle working with many
      noninteracting harmonic oscillators is established. The refrigeration cycle
      consists of two adiabatic and two constant-frequency processes. The general
      performance characteristics of the cycle are investigated, based on the quantum
      master equation and the semigroup approach. The expressions for several important
      performance parameters such as the coefficient of performance, cooling rate,
      power input, and rate of entropy production are derived. By using numerical
      solutions, the cooling rate of the refrigeration cycle subject to finite cycle
      duration is optimized. The maximum cooling rate and the corresponding parameters
      are calculated numerically. The optimal region of the coefficient of performance
      and the optimal ranges of temperatures of the working substance and times spent
      on the two constant-frequency processes are determined. Moreover, the optimal
      performance of the cycle in the high-temperature limit is compared with that of a
      classical Brayton refrigerator working with an ideal gas. The results obtained
      here show that in the high-temperature limit a harmonic quantum Brayton cycle may
      be equivalent to a classical Brayton cycle.

PMID- 14682857
TI  - Bose-Einstein condensation in random directed networks.
AB  - We consider the phenomenon of Bose-Einstein condensation in a random growing
      directed network. The network grows by the addition of vertices and edges. At
      each time step the network gains a vertex with probability p and an edge with
      probability 1-p. The new vertex has a fitness (a,b) a,b>0, with probability
      f(a,b). A vertex with fitness (a,b), with in-degree i and out-degree j, gains a
      new incoming edge with rate a(i+1) and an outgoing edge with rate b(j+1). The
      Bose-Einstein condensation occurs as a function of fitness distribution f(a,b).

PMID- 14682858
TI  - Synchronization in coupled map lattices as an interface depinning.
AB  - We study a solid-on-solid (SOS) model whose dynamics is inspired by recent
      studies of the synchronization transition in coupled map lattices (CML). The
      synchronization of CML is thus related with a depinning of interface from a
      binding wall. Critical behavior of our SOS model depends on a specific form of
      binding (i.e., transition rates of the dynamics). For an exponentially decaying
      binding the depinning belongs to the directed percolation universality class.
      Other types of depinning, including the one with a line of critical points, are
      observed for a power-law binding.

PMID- 14682859
TI  - Incomplete relaxation in a two-mass one-dimensional self-gravitating system.
AB  - Due to the apparent ease with which they can be numerically simulated, one
      dimensional gravitational systems were first introduced by astronomers to explore
      different modes of gravitational evolution. These include violent relaxation and
      the approach to thermal equilibrium. Careful work by dynamicists and statistical
      physicists has shown that several claims made by astronomers regarding these
      models were incorrect. Unusual features of the evolution include the development
      of long lasting structures on large scales, which can be thought of as one
      dimensional analogs of Jupiter's red spot or a galactic spiral density wave or
      bar. The existence of these structures demonstrates that in gravitational systems
      evolution is not entirely dominated by the second law of thermodynamics and also
      appears to contradict the Arnold diffusion ansatz. Thus it is correct to assert
      that the one-dimensional planar sheet gravitational system is the nonextensive
      analog of the Fermi-Pasta-Ulam model of dynamical systems. This paper is an
      extension of a preliminary study where we conclusively showed mass segregation
      and equipartition of kinetic energy in a two-mass planar sheet system for the
      first time. Here we employ both mean-field theory and dynamical simulation to
      more thoroughly probe the statistical and ergodic properties of these systems.
      Valuable information is obtained from local and global time averaging, and
      temporal and spatial correlation functions. Using these tools we show that the
      system appears to approach the equilibrium distribution on very long time scales,
      but the relaxation is incomplete.

PMID- 14682860
TI  - Effect of aging on network structure.
AB  - In network evolution, the effect of aging is universal: in scientific
      collaboration network, scientists have a finite time span of being active; in
      movie actors network, once popular stars are retiring from stage; devices on the
      Internet may become outmoded with techniques developing so rapidly. Here we find
      in citation networks that this effect can be represented by an exponential decay
      factor, e(-betatau), where tau is the node age, while other evolving networks
      (the Internet, for instance) may have different types of aging, for example, a
      power-law decay factor, which is also studied and compared. It has been found
      that as soon as such a factor is introduced to the Barabasi-Albert scale-free
      model, the network will be significantly transformed. The network will be
      clustered even with infinitely large size, and the clustering coefficient varies
      greatly with the intensity of the aging effect, i.e., it increases linearly with
      beta for small values of beta and decays exponentially for large values of beta.
      At the same time, the aging effect may also result in a hierarchical structure
      and a disassortative degree-degree correlation. Generally the aging effect will
      increase the average distance between nodes, but the result depends on the type
      of the decay factor. The network appears like a one-dimensional chain when
      exponential decay is chosen, but with power-law decay, a transformation process
      is observed, i.e., from a small-world network to a hypercubic lattice, and to a
      one-dimensional chain finally. The disparities observed for different choices of
      the decay factor, in clustering, average node distance, and probably other
      aspects not yet identified, are believed to bear significant meaning on empirical
      data acquisition.

PMID- 14682861
TI  - Queuing transitions in the asymmetric simple exclusion process.
AB  - Stochastic driven flow along a channel can be modeled by the asymmetric simple
      exclusion process. We confirm numerically the presence of a dynamic queuing phase
      transition at a nonzero obstruction strength, and establish its scaling
      properties. Below the transition, the traffic jam is macroscopic in the sense
      that the length of the queue scales linearly with system size. Above the
      transition, only a power-law shaped queue remains. Its density profile scales as
      deltarho approximately x(-nu) with nu=1/3, and x is the distance from the
      obstacle. We construct a heuristic argument, indicating that the exponent nu=1/3
      is universal and independent of the dynamic exponent of the underlying dynamic
      process. Fast bonds create only power-law shaped depletion queues, and with an
      exponent that could be equal to nu=2/3, but the numerical results yield
      consistently somewhat smaller values nu approximately 0.63(3). The implications
      of these results to faceting of growing interfaces and localization of directed
      polymers in random media, both in the presence of a columnar defect are pointed
      out as well.

PMID- 14682862
TI  - Generalized master equation via aging continuous-time random walks.
AB  - We discuss the problem of the equivalence between continuous-time random walk
      (CTRW) and generalized master equation (GME). The walker, making instantaneous
      jumps from one site of the lattice to another, resides in each site for extended
      times. The sojourn times have a distribution density psi(t) that is assumed to be
      an inverse power law with the power index micro. We assume that the Onsager
      principle is fulfilled, and we use this assumption to establish a complete
      equivalence between GME and the Montroll-Weiss CTRW. We prove that this
      equivalence is confined to the case where psi(t) is an exponential. We argue that
      is so because the Montroll-Weiss CTRW, as recently proved by Barkai [E. Barkai,
      Phys. Rev. Lett. 90, 104101 (2003)], is nonstationary, thereby implying aging,
      while the Onsager principle is valid only in the case of fully aged systems. The
      case of a Poisson distribution of sojourn times is the only one with no aging
      associated to it, and consequently with no need to establish special initial
      conditions to fulfill the Onsager principle. We consider the case of a
      dichotomous fluctuation, and we prove that the Onsager principle is fulfilled for
      any form of regression to equilibrium provided that the stationary condition
      holds true. We set the stationary condition on both the CTRW and the GME, thereby
      creating a condition of total equivalence, regardless of the nature of the
      waiting-time distribution. As a consequence of this procedure we create a GME
      that is a bona fide master equation, in spite of being non-Markov. We note that
      the memory kernel of the GME affords information on the interaction between
      system of interest and its bath. The Poisson case yields a bath with infinitely
      fast fluctuations. We argue that departing from the Poisson form has the effect
      of creating a condition of infinite memory and that these results might be useful
      to shed light on the problem of how to unravel non-Markov quantum master
      equations.

PMID- 14682863
TI  - Fermi-Pasta-Ulam beta lattice: Peierls equation and anomalous heat conductivity.
AB  - The Peierls equation is considered for the Fermi-Pasta-Ulam beta lattice.
      Explicit form of the linearized collision operator is obtained. Using this form
      the decay rate of the normal-mode energy as a function of wave vector k is
      estimated to be proportional to k(5/3). This leads to the t(-3/5) long-time
      behavior of the current correlation function, and, therefore, to the divergent
      coefficient of heat conductivity. These results are in good agreement with the
      results of recent computer simulations. Compared to the results obtained through
      the mode coupling theory our estimations give the same k dependence of the decay
      rate but a different temperature dependence. Using our estimations we argue that
      adding a harmonic on-site potential to the Fermi-Pasta-Ulam beta lattice may lead
      to finite heat conductivity in this model.

PMID- 14682864
TI  - Analysis of common attacks in public-key cryptosystems based on low-density
      parity-check codes.
AB  - We analyze the security and reliability of a recently proposed class of public
      key cryptosystems against attacks by unauthorized parties who have acquired
      partial knowledge of one or more of the private key components and/or of the
      plaintext. Phase diagrams are presented, showing critical partial knowledge
      levels required for unauthorized decryption.

PMID- 14682865
TI  - Quantization of classical maps with tunable Ruelle-Pollicott resonances.
AB  - We investigate the correspondence between the decay of correlation in classical
      systems, governed by Ruelle-Pollicott resonances, and the properties of the
      corresponding quantum systems. For this purpose we construct classical dynamics
      with controllable resonances together with their quantum counterparts. As an
      application of such tunable resonances we reveal the role of Ruelle-Pollicott
      resonances for the localization properties of quantum energy eigenstates.

PMID- 14682866
TI  - Control of dynamical localization.
AB  - Control over the quantum dynamics of chaotic kicked rotor systems is
      demonstrated. Specifically, control over a number of quantum coherent phenomena
      is achieved by a simple modification of the kicking field. These include the
      enhancement of the dynamical localization length, the introduction of classical
      anomalous diffusion assisted control for systems far from the semiclassical
      regime, and the observation of a variety of strongly nonexponential line shapes
      for dynamical localization. The results provide excellent examples of controlled
      quantum dynamics in a system that is classically chaotic and offer opportunities
      to explore quantum fluctuations and correlations in quantum chaos.

PMID- 14682867
TI  - Self-organization of quantum dots in epitaxially strained solid films.
AB  - A nonlinear evolution equation for surface-diffusion-driven Asaro-Tiller-Grinfeld
      instability of an epitaxially strained thin solid film on a solid substrate is
      derived in the case where the film wets the substrate. It is found that the
      presence of a weak wetting interaction between the film and the substrate can
      substantially retard the instability and modify its spectrum in such a way that
      the formation of spatially regular arrays of islands or pits on the film surface
      becomes possible. It is shown that the self-organization dynamics is
      significantly affected by the presence of the Goldstone mode associated with the
      conservation of mass.

PMID- 14682868
TI  - Lyapunov exponents and the extensivity of dimensional loss for systems in thermal
      gradients.
AB  - An explicit relation between the dimensional loss (DeltaD), entropy production,
      and transport is established under thermal gradients, relating the microscopic
      and macroscopic behaviors of the system. The extensivity of DeltaD in systems
      with bulk behavior follows from the relation. The maximum Lyapunov exponents in
      thermal equilibrium and DeltaD in nonequilibrium depend on the choice of heat
      baths, while their product is unique and macroscopic. Finite-size corrections are
      also computed and all results are verified numerically.

PMID- 14682869
TI  - Exploring classical phase space structures of nearly integrable and mixed quantum
      systems via parametric variation.
AB  - The correlation between overlap intensities and level velocities has been
      introduced as a sensitive measure capable of revealing phase space localization.
      Previously applied to chaotic quantum systems, here we extend the theory to near
      integrable and mixed quantum systems. This measure is useful in the latter cases
      because it has the ability to highlight certain phase space structures depending
      upon the perturbation used to parametrically vary the Hamiltonian. A detailed
      semiclassical theory is presented relating the correlation coefficient to the
      phase space weighted derivatives of the classical action. In the process, we
      confront the question of whether the Hannay-Ozorio de Almeida sum rules are
      simply extendable to mixed phase space systems. In addition, the variant Planck's
      over 2pi scalings of the correlation coefficient and relevant quantities are
      derived for nearly integrable systems. Excellent agreement is found between the
      theory and the results for integrable billiards as well as for the standard map.

PMID- 14682870
TI  - Transverse instabilities in chemical Turing patterns of stripes.
AB  - We present a theoretical and experimental study of the sideband instabilities in
      Turing patterns of stripes. We compare numerical computations of the Brusselator
      model with experiments in a chlorine dioxide-iodine-malonic acid (CDIMA) reaction
      in a thin gel layer reactor in contact with a continuously refreshed reservoir of
      reagents. Spontaneously evolving Turing structures in both systems typically
      exhibit many defects that break the symmetry of the pattern. Therefore, the study
      of sideband instabilities requires a method of forcing perfect, spatially
      periodic Turing patterns with the desired wave number. This is easily achieved in
      numerical simulations. In experiments, the photosensitivity of the CDIMA reaction
      permits control and modulation of Turing structures by periodic spatial
      illumination with a wave number outside the stability region. When a too big wave
      number is imposed on the pattern, the Eckhaus instability may arise, while for
      too small wave numbers an instability sets in forming zigzags. By means of the
      amplitude equation formalism we show that, close to the hexagon-stripe
      transitions, these sideband instabilities may be preceded by an amplitude
      instability that grows transient spots locally before reconnecting with stripes.
      This prediction is tested in both the reaction-diffusion model and the
      experiment.

PMID- 14682871
TI  - Dual synchronization of chaos in Colpitts electronic oscillators and its
      applications for communications.
AB  - We demonstrate the dual synchronization of chaos in two pairs of one-way coupled
      Colpitts electronic oscillators by both experiment and numerical simulation. We
      use the cross coupling method, where the difference in voltage between the sum of
      two master oscillators and one slave oscillator is injected into the other slave
      oscillator as an electrical current, for dual synchronization of chaos. We have
      investigated the regions for achieving dual synchronization of chaos when one of
      the internal parameters is mismatched between the master and slave oscillators.
      We numerically obtain a similar curve for the accuracy of synchronization to that
      obtained from our experiments. A communication scheme using dual synchronization
      of chaos is also proposed and demonstrated.

PMID- 14682872
TI  - Semiclassical evaluation of quantum fidelity.
AB  - We present a numerically feasible semiclassical (SC) method to evaluate quantum
      fidelity decay (Loschmidt echo) in a classically chaotic system. It was thought
      that such evaluation would be intractable, but instead we show that a uniform SC
      expression not only is tractable but it also gives remarkably accurate numerical
      results for the standard map in both the Fermi-golden-rule and Lyapunov regimes.
      Because it allows Monte Carlo evaluation, the uniform expression is accurate at
      times when there are 10(70) semiclassical contributions. Remarkably, it also
      explicitly contains the "building blocks" of analytical theories of recent
      literature, and thus permits a direct test of the approximations made by other
      authors in these regimes, rather than an a posteriori comparison with numerical
      results. We explain in more detail the extended validity of the classical
      perturbation approximation and show that within this approximation, the so-called
      "diagonal approximation" is automatic and does not require ensemble averaging.

PMID- 14682873
TI  - Lyapunov exponent of ion motion in microplasmas.
AB  - Dynamical chaos is studied in the Hamiltonian motion of ions confined in a
      Penning trap and forming so-called microplasmas. The dynamical chaos of the ion
      motion is characterized by the maximum Lyapunov exponent. Results are reported on
      the dependence of this exponent on the energy of the system, on the number of
      ions, as well as on the geometry of the trap. Different dynamical regimes are
      characterized from the crystalline state to a strongly chaotic regime, and to
      quasiharmonic motion in the external potential of the trap. Across these regimes,
      the Lyapunov exponent increases, reaches a maximum value, and decreases as a
      function of energy. Besides, the maximum value of the Lyapunov exponent increases
      as a function of the number of ions.

PMID- 14682874
TI  - Constructing constrained invariant sets in multiscale continuum systems.
AB  - We present a method that we name the constrained invariant manifold method, a
      visualization tool to construct stable and unstable invariant sets of a map or
      flow, where the invariant sets are constrained to lie on a slow invariant
      manifold. The construction of stable and unstable sets constrained to an unstable
      slow manifold is exemplified in a singularly perturbed model arising from a
      structural-mechanical system consisting of a pendulum coupled to a viscoelastic
      rod. Additionally, we extend the step and stagger method [D. Sweet, H. Nusse, and
      J. Yorke, Phys. Rev. Lett. 86, 2261 (2001)] to calculate a delta pseudoorbit on a
      chaotic saddle constrained to the slow manifold in order to be able to compute
      the Lyapunov exponents of the saddle.

PMID- 14682875
TI  - Semiclassical study on tunneling processes via complex-domain chaos.
AB  - We investigate the semiclassical mechanism of tunneling processes in
      nonintegrable systems. The significant role of complex-phase-space chaos in the
      description of the tunneling processes is elucidated by studying a kicked
      scattering model. Behaviors of tunneling orbits are encoded into symbolic
      sequences based on the structure of a complex homoclinic tangle. By means of the
      symbolic coding, the phase space itineraries of tunneling orbits are related with
      the amounts of imaginary parts of actions gained by the orbits, so that the
      systematic search of dominant tunneling orbits becomes possible.

PMID- 14682876
TI  - Perturbation of period-2 oscillations in catalytic reactions accompanied by
      surface restructuring.
AB  - We present Monte Carlo simulations illustrating the effect of periodic forcing on
      period-2 oscillations related to the interplay of catalytic reaction and surface
      restructuring. The oscillations are found to be fairly stable if the external
      frequency equals the main internal frequency. In contrast, perturbations with
      other frequencies may easily change the type of oscillation. In particular,
      perturbations with double frequency convert period-2 oscillations into period-1
      oscillations with the imposed frequency.

PMID- 14682877
TI  - Floquet-Bloch operator for the Bose-Hubbard model with static field.
AB  - This paper deals with the spectral properties of the one-dimensional Bose-Hubbard
      Hamiltonian amended by an external static field-a model for cold spinless atoms
      loaded in a quasi-one-dimensional optical lattice and subject to an additional
      static (for example, gravitational) force. The analysis is performed in terms of
      the Floquet-Bloch operator, defined as the evolution operator of the system over
      one Bloch period. Depending on the particular choice of parameters, the spectrum
      is found to be either regular or chaotic. Moreover, in the chaotic case, the
      matrix of the Floquet-Bloch operator is well characterized as a random matrix of
      the circular orthogonal ensemble.

PMID- 14682878
TI  - Toroidal bubbles with circulation in ideal hydrodynamics: a variational approach.
AB  - Incompressible, inviscid, irrotational, unsteady flows with circulation Gamma
      around a distorted toroidal bubble are considered. A general variational
      principle that determines the evolution of the bubble shape is formulated. For a
      two-dimensional (2D) cavity with a constant area A, exact pseudodifferential
      equations of motion are derived, based on variables that determine a conformal
      mapping of the unit circle exterior into the region occupied by the fluid. A
      closed expression for the Hamiltonian of the 2D system in terms of canonical
      variables is obtained. Stability of a stationary drifting 2D hollow vortex is
      demonstrated, when the gravity is small, gA(3/2)/Gamma(2)<<1. For a circulation
      dominated regime of three-dimensional flows a simplified Lagrangian is suggested,
      inasmuch as the bubble shape is well described by the center line R(xi,t) and by
      an approximately circular cross section with relatively small area,
      A(xi,t)<<(contour integral operator |R'|dxi)(2). In particular, a finite
      dimensional dynamical system is derived and approximately solved for a vertically
      moving axisymmetric vortex ring bubble with a compressed gas inside.

PMID- 14682879
TI  - Lattice-Boltzmann model based on field mediators for immiscible fluids.
AB  - In this paper, a lattice BGK (Bhatnagar-Gross-Krook) model is proposed for
      immiscible fluids. Collision operator is decoupled considering mutual and cross
      collisions between lattice particles, with three independent parameters related
      to the species diffusivity and to the viscosity of each fluid. Field mediator's
      concept, described by Santos and Philippi [Phys. Rev. E 65, 046305 (2002)], is
      extended to the framework of the lattice-Boltzmann equation and interference
      between mediators and particles is modeled by considering that there is a
      deviation in particles velocity, proportional to the mediators' distribution at
      the site. A Chapman-Enskog analysis is performed leading to theoretical
      predictions of the macroscopic equations inside the transition layer and to the
      transition-layer thickness. Chapman-Enskog analysis is restricted to near
      equilibrium states and was unable to predict the correct second-order interfacial
      tension dependence on the modeled long-range fields intensity. Interfacial
      tension was, only, correctly retrieved using a nonequilibrium solution.
      Theoretical predictions are compared with simulation results and the model is
      tested considering its ability in describing the dynamical behavior of the
      interface and Galilean invariance.

PMID- 14682880
TI  - Interaction of trailing vortices in the wake of a wall-mounted rectangular
      cylinder.
AB  - Numerical simulations are performed to investigate three-dimensional unsteady
      vortex-vortex and vortex-surface interactions in the near field of a wall-mounted
      rectangular cylinder placed inside a channel. The generation mechanism of the
      upstream and the trailing vortices from the topologically important critical
      points and their near-wall evolution pattern have been examined in detail. In the
      upstream region, a laminar necklace vortex system formed around the junction
      between the rectangular block (cylinder) and the flat channel floor. A sequence
      of streamwise vortical rollers dominated the downstream interaction region, and
      they exhibited strong unsteady vortex-surface interaction. Streamwise vortices
      which formed upstream of the obstacle exhibited quadrupole structure with the
      dominant pair being central downwash, whereas those lifting the flow behind the
      obstacle were of predominantly central upwash. Notably, at some downstream
      location, the near-wall wake structure was observed to locally disappear due to
      mutual interaction and annihilation by opposite strength vortices on either side
      of the wake centerline. During the entire course of unsteady flow evolution, such
      a disappearance of the wake remained closely associated with local contraction of
      the limiting streamlines on the channel floor, the development of a pair of
      topologically important floor critical points (saddles), and the presence of a
      near-wall node on the vertical symmetry plane. The dominance of inward transverse
      flow toward these saddles together with flow evolution from the downstream node
      on the vertical symmetry plane were found to be particularly responsible for
      facilitating the local interaction of various vortices of opposite strength,
      leading to significant vorticity cancellation in the region. Moreover, the basic
      source of the wake vortices and their nature of evolution behind the cylinder
      were also investigated here, and they were found to be fundamentally different
      from what one usually observes in the near-wake of a transverse jet. However, the
      growth of a pair of vertically lifting vortices from the spiraling shear layer
      nodes just behind the downstream edge of the cylinder base was detected in this
      flow configuration also.

PMID- 14682881
TI  - Stretching, alignment, and shear in slowly varying velocity fields.
AB  - We derive criteria that locate intense material stretching and shear in two
      dimensional flows with slow time dependence. Our derivation makes use of the near
      integrability of the equation of variations along trajectories of the slowly
      varying flow. The criteria yield two diagnostic scalar fields for use in real
      time Lagrangian predictions in geophysical flows.

PMID- 14682882
TI  - Inertially driven buckling and overturning of jets in a Hele-Shaw cell.
AB  - We study a fluid jet descending through stratified surroundings at low Reynolds
      number in Hele-Shaw flow. The jet buckles and overturns inside a conduit of
      entrained fluid which supports smooth or unstable traveling waves. A model of the
      recirculating flow within the conduit shows that buckling and waves arise from
      Kelvin-Helmholtz instabilities and quantitatively accounts for the main
      experimental observations. Beyond the onset of the instability, a damped, forced
      Burgers' equation obtained from corrections to Darcy's law for small Reynolds
      number governs the interface dynamics and supports singularities corresponding to
      the observed jet overturning and unstable waves.

PMID- 14682883
TI  - Nonequilibrium kinetics of a radiative CO flow behind a shock wave.
AB  - An investigation is presented of a highly nonequilibrium CO flow with
      consistently coupled vibrational energy exchanges, chemical reactions, and
      radiation. A detailed state-to-state model taking into account vibration
      vibration, vibration-translation, and vibration-electronic transitions,
      dissociation-recombination reactions, and radiative transitions between
      vibrational and electronic states is developed on the basis of kinetic theory
      methods. A closed set of master equations for vibration-electronic level
      populations, number densities of atomic species, radiation intensity,
      temperature, and velocity is derived, and a one-dimensional inviscid carbon
      monoxide flow behind a plane shock wave is studied numerically. Several models of
      vibrational transition and dissociation rates in high temperature carbon monoxide
      are tested, and a model satisfying both accuracy and feasibility requirements is
      recommended. The role of various energy transfers and chemical reactions in the
      formation of nonequilibrium vibrational distributions in a shock heated CO flow
      is studied, and the influence of state-to-state distributions on macroscopic flow
      parameters and radiation intensity is discussed.

PMID- 14682884
TI  - Reactive dynamics of inertial particles in nonhyperbolic chaotic flows.
AB  - Anomalous kinetics of infective (e.g., autocatalytic) reactions in open,
      nonhyperbolic chaotic flows are important for many applications in biological,
      chemical, and environmental sciences. We present a scaling theory for the
      singular enhancement of the production caused by the universal, underlying
      fractal patterns. The key dynamical invariant quantities are the effective
      fractal dimension and effective escape rate, which are primarily determined by
      the hyperbolic components of the underlying dynamical invariant sets. The theory
      is general as it includes all previously studied hyperbolic reactive dynamics as
      a special case. We introduce a class of dissipative embedding maps for numerical
      verification.

PMID- 14682885
TI  - Standing waves in flow between finite counterrotating cylinders.
AB  - Experimental evidence for standing waves resulting from a supercritical Hopf
      bifurcation that appears as the first pattern-forming instability in
      counterrotating Taylor-Couette flow is presented. Depending on the aspect ratio
      two different types of standing waves, denoted as SW0 and SW(pi), could be
      observed. Both modes have an azimuthal wave number m=1 but differ in symmetry.
      While for SW(pi), a spatiotemporal glide-reflection symmetry could be found, SW0
      is purely spatial reflection symmetric. The transition between the two modes is
      found to be organized in a cusp bifurcation unfolded by variations of the aspect
      ratio. The "classical" spiral vortex flow appears in this control parameter
      regime only as a result of a secondary steady bifurcation from SW0. This
      transition is found to be either subcritical or supercritical. The experimentally
      observed bifurcation structure has been predicted by theory of Hopf bifurcation
      to spiral vortex flow in finite counterrotating Taylor-Couette systems.

PMID- 14682886
TI  - Convection in a very compressible fluid: comparison of simulations with
      experiments.
AB  - The time profile DeltaT(t) of the temperature difference, measured across a very
      compressible fluid layer of supercritical 3He after the start of a heat flow,
      shows a damped oscillatory behavior before steady-state convection is reached.
      The results for DeltaT(t) obtained from numerical simulations and from laboratory
      experiments are compared over a temperature range where the compressibility
      varies by a factor of approximately 40. First the steady-state convective heat
      current j(conv) as a function of the Rayleigh number Ra is presented, and the
      agreement is found to be good. Second, the shape of the time profile and two
      characteristic times in the transient part of DeltaT(t) from simulations and
      experiments are compared, namely (1) t(osc), the oscillatory period, and (2)
      t(p), the time of the first peak after starting the heat flow. These times,
      scaled by the diffusive time tau(D) versus Ra, are presented. The agreement is
      good for t(osc)/tau(D), where the results collapse on a single curve showing a
      power-law behavior. The simulation hence confirms the universal scaling behavior
      found experimentally. However for t(p)/tau(D), where the experimental data also
      collapse on a single curve, the simulation results show systematic departures
      from such a behavior. A possible reason for some of the disagreements, both in
      the time profile and in t(p), is discussed.

PMID- 14682887
TI  - Anisotropy in homogeneous rotating turbulence.
AB  - The effective stress tensor of a homogeneous turbulent rotating fluid is
      anisotropic. This leads us to consider the most general axisymmetric four-rank
      "viscosity tensor" for a Newtonian fluid and the new terms in the turbulent
      effective force on large scales that arise from it, in addition to the
      microscopic viscous force. Some of these terms involve couplings to vorticity and
      others are angular momentum nonconserving (in the rotating frame). Furthermore,
      we explore the constraints on the response function and the two-point velocity
      correlation due to axisymmetry. Finally, we compare our viscosity tensor with
      other four-rank tensors defined in current approaches to nonrotating anisotropic
      turbulence.

PMID- 14682888
TI  - Molecular-dynamic calculation of the relaxation of the electron energy
      distribution function in a plasma.
AB  - A molecular-dynamic (MD) code is used to calculate the temporal evolution of
      nonequilibrium electron distribution functions in plasmas. To the authors'
      knowledge, this is the first time that a molecular-dynamic code has been used to
      treat this problem using a macroscopic number of particles. The code belongs to
      the class of P3M (particle-particle-particle-mesh) codes. Since the equations
      solved by the MD code are fundamental, this approach avoids several assumptions
      that are inherent to alternative methods. For example, the initial energy
      distribution can be arbitrary, and there is no need to assume a value for the
      Coulomb logarithm. The advantages of the MD code are illustrated by comparing its
      results with those of Monte Carlo and Fokker-Planck codes with a set of plasma
      parameters for which the Fokker-Planck calculation is shown to give incorrect
      results. As an example, we calculate the relaxation of the electron energy
      distribution produced by optical field ionization of a mixed plasma containing
      argon and hydrogen.

PMID- 14682889
TI  - Relativistic electron acceleration in focused laser fields after above-threshold
      ionization.
AB  - Electrons produced as a result of above-threshold ionization of high-Z atoms can
      be accelerated by currently producible laser pulses up to GeV energies, as shown
      recently by Hu and Starace [Phys. Rev. Lett. 88, 245003 (2002)]. To describe
      electron acceleration by general focused laser fields, we employ an analytical
      model based on a Hamiltonian, fully relativistic, ponderomotive approach. Though
      the above-threshold ionization represents an abrupt process compared to laser
      oscillations, the ponderomotive approach can still adequately predict the
      resulting energy gain if the proper initial conditions are introduced for the
      particle drift following the ionization event. Analytical expressions for
      electron energy gain are derived and the applicability conditions of the
      ponderomotive formulation are studied both analytically and numerically. The
      theoretical predictions are supported by numerical computations.

PMID- 14682890
TI  - Time-resolved pinhole camera imaging and extreme ultraviolet spectrometry on a
      hollow cathode discharge in xenon.
AB  - A pinhole camera, an extreme ultraviolet (EUV) spectrometer, a fast gatable
      multichannel plate EUV detector, and a digital camera have been installed on the
      ASML EUV laboratory setup to perform time-resolved pinhole imaging and EUV
      spectroscopy on a copy of the Philips EUV hollow cathode discharge plasma source.
      The main properties of the setup have been characterized. Time-resolved
      measurements within the plasma pulse in the EUV have been performed on this
      source. Specific features of the plasma, such as a ring shape in the initiation
      phase and a propagating sphere during the pinch phase, have either been
      discovered or confirmed experimentally. Relative populations of various
      ionization stages in the pinch plasma have been estimated on the basis of line
      intensities and calculated transition probabilities. The changes in relative line
      intensities of a single ionization stage can be explained by a combination of
      temperature and excitation/deexcitation balance effects. Experiments with argon
      dilution on a newer version of the source show considerable effect on the shape
      of the xenon EUV spectrum.

PMID- 14682891
TI  - Electric and magnetic field generation and target heating by laser-generated fast
      electrons.
AB  - The electric and magnetic fields generated by a beam of fast electrons in a
      conductor are calculated analytically, including the change in resistivity due to
      Ohmic heating. It is assumed that the resistivity has an arbitrary power law
      dependence on temperature, the fast electron current density is fixed (rigid
      beam), charge neutralization is instantaneous, and that magnetic diffusion is
      negligible. The implications for high-intensity laser-solid interactions are
      discussed. The minimum fast electron density for fast ignition by Ohmic heating
      is given, and found to be unrealistically high.

PMID- 14682892
TI  - Observation of ion acoustic waves associated with plasma-induced incoherence of
      laser beams using Thomson scattering.
AB  - We have carried out experiments to investigate the physical processes responsible
      for the recently discovered phenomenon of plasma-induced incoherence (PII) of a
      laser beam. Using a Thomson scattering diagnostic, we have observed ion acoustic
      waves (IAW) having wave vectors transverse to the interaction beam spectral and
      temporal characteristics of which show a clear correlation with other signatures
      of PII for various conditions of plasma density and laser intensity. These
      results support the recent theoretical interpretation for which the IAW result
      from the coupling between forward stimulated Brillouin scattering and self
      focusing of the laser light in PII mechanisms.

PMID- 14682893
TI  - Dynamic confinement of targets heated quasi-isochorically with heavy ion beams.
AB  - Isochoric heating of matter by intense heavy ion beams promises to become a
      fruitful approach to warm dense matter studies. For heating times that are long
      on the hydrodynamic time scale of the target response a tamped target is
      essential. The proposed dynamic confinement provides homogeneous target heating
      by a low-Z tamper, which allows one to apply powerful x-ray scattering
      diagnostics. To demonstrate the potential of the method, heating of a hydrogen
      sample with the SIS-18 beam at GSI Darmstadt is investigated numerically. The
      intense x-ray bursts for diagnostics can be provided by the PHELIX laser
      currently installed at GSI. In the optimized heating regime, density variations
      can be reduced to a level of 15% from the initial density value.

PMID- 14682894
TI  - Bifurcation points in the theory of axially symmetric arc cathodes.
AB  - Steady-state current transfer from arc plasmas to axially symmetric cathodes is
      treated in the framework of the model of nonlinear surface heating. An approach
      is developed to calculate the bifurcation points at which three-dimensional spot
      mode solutions branch off from solutions describing the diffuse mode and axially
      symmetric spot modes. In particular, the first bifurcation point positioned on
      the diffuse-mode solution has been calculated, and thus its stability limit,
      i.e., the current below which the diffuse mode becomes unstable. Calculation
      results are given for the case of a tungsten cathode in the form of a circular
      cylinder in high-pressure plasmas. The effect produced on the stability limit by
      variations of control parameters (cathode dimensions, work function of the
      cathode material, plasma-producing gas, and its pressure) is studied and found to
      conform to trends observed experimentally. The stability limit is found to be
      much more sensitive to variations of control parameters than characteristics of
      the diffuse mode are, the strongest effect being produced by variations of
      cathode dimensions and of the work function of the cathode material. This finding
      conforms to the fact that the diffuse-spot transition is difficult to reproduce
      in the experiment.

PMID- 14682895
TI  - Spatial characteristics of Kalpha x-ray emission from relativistic femtosecond
      laser plasmas.
AB  - The spatial structure of the Kalpha emission from Ti targets irradiated with a
      high intensity femtosecond laser has been studied using a two-dimensional
      monochromatic imaging technique. For laser intensities I<5 x 10(17) W/cm(2), the
      observed spatial structure of the Kalpha emission can be explained by the
      scattering of the hot electrons inside the solid with the help of a hybrid
      particle-in-cell/Monte Carlo model. By contrast, at the maximum laser intensity
      I=7 x 10(18) W/cm(2) the half-width of the Kalpha emission was 70 microm compared
      to a laser-focus half-width of 3 microm. Moreover, the main Kalpha peak was
      surrounded by a halo of weak Kalpha emission with a diameter of 400 microm and
      the Kalpha intensity at the source center did not increase with increasing laser
      intensity. These three features point to the existence of strong self-induced
      fields, which redirect the hot electrons over the target surface.

PMID- 14682896
TI  - Compressional and shear wakes in a two-dimensional dusty plasma crystal.
AB  - Wakes composed of compressional and shear waves were studied experimentally in a
      two-dimensional screened-Coulomb crystal. Highly charged microspheres suspended
      in a plasma settled in a horizontal monolayer and arranged in a triangular
      lattice with a repulsive interparticle potential. Wakes were excited by a moving
      spot of Ar+ laser light. Depending on the laser spot speed, compressional waves
      formed a Mach cone and multiple lateral or transverse wakes, similar to ship
      wakes on the water surface, due to a combination of acoustic and dispersive
      properties. Shear waves, however, formed only a Mach cone, due to their nearly
      acoustic, i.e., dispersionless character. The experimental results show agreement
      with a recently developed theory and with molecular dynamics simulations, which
      assume a binary Yukawa interparticle potential. A generally useful method is
      presented for calculating the real part of the dispersion relation of the
      compressional waves based on the analysis of the spatial structure of a phonon
      wake. Fitting the resulting dispersion relation provides an independent measure
      of the interparticle potential, parametrized by the screening parameter kappa and
      particle charge Q.

PMID- 14682897
TI  - Calculation of ionization balance and electrical conductivity in nonideal
      aluminum plasma.
AB  - A practical approach has been implemented to calculate the ionization balance and
      electrical conductivity of warm dense aluminum plasma with the Coulomb coupling
      effect taken into account. The correction term for ionization potential is
      formulated with a number of basic dimensionless parameters that characterize
      nonideal plasma and incorporated with the fitted formulas of excess free energy
      given by Tanaka, Mitake, and Ichimaru [Phys. Rev. A 32, 1896 (1985)] and Chabrier
      and Potekhin [Phys. Rev. E 58, 4941 (1998)] to determine the ionization balance
      in an equilibrium state. The calculated degree of ionization of aluminum plasma
      exhibits a sudden increase near the solid density approximately 1 g/cm(3) at
      temperatures of a few eV, which effectively demonstrates the pressure-induced
      ionization. The electrical conductivity is evaluated in a partially ionized
      plasma regime based on a linear mixture rule that takes into account both the
      electron-ion and electron-neutral collisions and then the computed results are
      compared with available data from recent experiments. It is shown that the
      calculation well reproduces the overall trend of measured electrical conductivity
      of nonideal aluminum plasma accounting for the metal-insulator transition.

PMID- 14682898
TI  - Phase dependence of relativistic electron dynamics and emission spectra in the
      superposition of an ultraintense laser field and a strong uniform magnetic field.
AB  - The phase dependence of the dynamics and emission spectra of a fully relativistic
      electron in the superposition of an ultraintense plane wave laser field and a
      strong uniform magnetic field has been investigated. It is found that the effect
      of changing the initial laser phase is quite different for circularly and
      linearly polarized laser fields. For circular polarization only the axis of the
      helical trajectory is changed with variation of the initial laser field phase.
      However, for linear polarization, the effect of changing the initial phase is
      opposite in the two parameter regions divided by the resonance condition r=1 (r
      stands for the ratio between the reduced cyclotron frequency and laser
      frequency). When r<1, with increase in the initial laser field phase eta(0) from
      0 to pi/2, both the radius of the electron's helical trajectory and the height of
      the peak related to the uniform magnetic field are decreased, and these two
      physical values are increased with an increase in the laser initial phase when
      r>1. The phase dependence of the electron's energy and velocity components was
      also studied. Some beat structure is found when eta(0)=0 and this structure is
      absent when eta(0)=pi/2.

PMID- 14682899
TI  - Stimulated Raman scattering of intense laser pulses in air.
AB  - Stimulated rotational Raman scattering (SRRS) is known to be one of the processes
      limiting the propagation of high-power laser beams in the atmosphere. In this
      paper, SRRS, Kerr nonlinearity effects, and group velocity dispersion of short
      laser pulses and pulse trains are analyzed and simulated. Fully time-dependent,
      three-dimensional, nonlinear propagation equations describing the Raman
      interaction, optical Kerr nonlinearity due to bound electrons, and group velocity
      dispersion are presented and discussed. The effective time-dependent nonlinear
      refractive index containing both Kerr and Raman processes is derived. Linear
      stability analysis is used to obtain growth rates and phase matching conditions
      for the SRRS, modulational, and filamentation instabilities. Numerical solutions
      of the propagation equations in three dimensions show the detailed evolution of
      the Raman scattering instability for various pulse formats. The dependence of the
      growth rate of SRRS on pulse duration is examined and under certain conditions it
      is shown that short (approximately psec) laser pulses are stable to the SRRS
      instability. The interaction of pulses in a train through the Raman polarization
      field is also illustrated.

PMID- 14682900
TI  - Correlation decay and partial coherence in nonlinear wave interactions.
AB  - In the present analysis we study the broad-band triplet interaction in regimes of
      large amplitudes. Linear response theories associated with nonlinear arguments
      are used to show that even though coherence of high-frequency modes is lost as
      one first encounters chaotic regimes, it can be restored as field amplitudes grow
      further. We discuss implications of the feature for fixed-phase interactions.

PMID- 14682901
TI  - Diffractive properties of volume phase gratings in photorefractive sillenite
      crystals of arbitrary cut under the influence of an external electric field.
AB  - We study the influence of bias dc electric field on the optical properties of
      volume phase gratings formed in optically active photorefractive sillenite
      crystals. By considering a general case where the external electric bias
      direction, the grating vector orientation, the light propagation direction
      (crystal cut), and state of polarization are arbitrary, we deduce analytical
      expressions for the diffraction efficiency and the polarization state of the
      diffracted beam. The influence of the inverse piezoelectric effect is taken into
      account both in the uniform and the spatially varying part of the impermeability
      tensor, as well as into the calculation of the effective static permittivity. A
      theoretical comparative study of the dynamic behavior of the diffraction
      efficiency as a function of the physical parameters that affect the diffraction
      process (crystal cut, electric bias, input polarization, and grating orientation)
      along with experimental verification is provided. The general analytical solution
      provides means of exploitation of the capabilities of sillenite crystals in
      several applications.

PMID- 14682902
TI  - Two-soliton collisions in a near-integrable lattice system.
AB  - We examine collisions between identical solitons in a weakly perturbed Ablowitz
      Ladik (AL) model, augmented by either onsite cubic nonlinearity (which
      corresponds to the Salerno model, and may be realized as an array of strongly
      overlapping nonlinear optical waveguides) or a quintic perturbation, or both.
      Complex dependences of the outcomes of the collisions on the initial phase
      difference between the solitons and location of the collision point are observed.
      Large changes of amplitudes and velocities of the colliding solitons are
      generated by weak perturbations, showing that the elasticity of soliton
      collisions in the AL model is fragile (for instance, the Salerno's perturbation
      with the relative strength of 0.08 can give rise to a change of the solitons'
      amplitudes by a factor exceeding 2). Exact and approximate conservation laws in
      the perturbed system are examined, with a conclusion that the small perturbations
      very weakly affect the norm and energy conservation, but completely destroy the
      conservation of the lattice momentum, which is explained by the absence of the
      translational symmetry in generic nonintegrable lattice models. Data collected
      for a very large number of collisions correlate with this conclusion. Asymmetry
      of the collisions (which is explained by the dependence on the location of the
      central point of the collision relative to the lattice, and on the phase
      difference between the solitons) is investigated too, showing that the
      nonintegrability-induced effects grow almost linearly with the perturbation
      strength. Different perturbations (cubic and quintic ones) produce virtually
      identical collision-induced effects, which makes it possible to compensate them,
      thus finding a special perturbed system with almost elastic soliton collisions.

PMID- 14682903
TI  - Polarization switching in a planar optical waveguide.
AB  - The multiscale expansion formalism is applied to the study of nonlinear planar
      optical waveguides. It allows us to describe the linear and nonlinear propagation
      for both transverse electric and transverse magnetic modes, and the interaction
      between them. An accurate computation of the nonlinear self- and cross-phase
      modulation coefficients allows one to give account of the polarization switching
      which has been observed experimentally.

PMID- 14682904
TI  - Multistable pulselike solutions in a parametrically driven Ginzburg-Landau
      equation.
AB  - It is well known that pulselike solutions of the cubic complex Ginzburg-Landau
      equation are unstable but can be stabilized by the addition of quintic terms. In
      this paper we explore an alternative mechanism where the role of the stabilizing
      agent is played by the parametric driver. Our analysis is based on the numerical
      continuation of solutions in one of the parameters of the Ginzburg-Landau
      equation (the diffusion coefficient c), starting from the nonlinear Schrodinger
      limit (for which c=0). The continuation generates, recursively, a sequence of
      coexisting stable solutions with increasing number of humps. The sequence
      "converges" to a long pulse which can be interpreted as a bound state of two
      fronts with opposite polarities.

PMID- 14682905
TI  - Stochastic series expansion method for quantum Ising models with arbitrary
      interactions.
AB  - A quantum Monte Carlo algorithm for the transverse Ising model with arbitrary
      short- or long-range interactions is presented. The algorithm is based on
      sampling the diagonal matrix elements of the power-series expansion of the
      density matrix (stochastic series expansion), and avoids the interaction
      summations necessary in conventional methods. In the case of long-range
      interactions, the scaling of the computation time with the system size N is
      therefore reduced from N2 to N ln(N). The method is tested on a one-dimensional
      ferromagnet in a transverse field, with interactions decaying as 1/r(2).

PMID- 14682906
TI  - Microcanonical optimization algorithm for the Euclidean Steiner problem in Rn
      with application to phylogenetic inference.
AB  - The Euclidean Steiner tree problem in R(n) (ESTP) is that of finding the shortest
      interconnecting network spanning p given nodes in the Euclidean R(n), with the
      possible use of extra nodes. Combinatorial explosion precludes the use of exact
      methods for large high-dimensional ESTP instances, but very few heuristic
      approaches have so far been proposed for them. Here we introduce a microcanonical
      optimization algorithm that works over a topology-describing data structure
      associated to the ESTP solutions, and which is proven able to find close-to
      minimum Steiner trees in reasonable computational time, even for configurations
      of up to p=50 points in n=50 dimensions. Moreover, its performance is shown to
      increase with n, which makes it especially suited for high-dimensional clustering
      problems such as those of phylogenetic inference, an instance of which is
      considered here.

PMID- 14682907
TI  - Direct simulation Monte Carlo method for the Uehling-Uhlenbeck-Boltzmann
      equation.
AB  - In this paper we describe a direct simulation Monte Carlo algorithm for the
      Uehling-Uhlenbeck-Boltzmann equation in terms of Markov processes. This provides
      a unifying framework for both the classical Boltzmann case as well as the Fermi
      Dirac and Bose-Einstein cases. We establish the foundation of the algorithm by
      demonstrating its link to the kinetic equation. By numerical experiments we study
      its sensitivity to the number of simulation particles and to the discretization
      of the velocity space, when approximating the steady-state distribution.

PMID- 14682908
TI  - Characterizing width uniformity by wave propagation.
AB  - This work describes a different image analysis approach to characterize the
      uniformity of objects in agglomerates by using the propagation of normal wave
      fronts. The problem of width uniformity is discussed and its importance for the
      characterization of composite structures normally found in physics and biology
      highlighted. The methodology involves identifying each cluster (i.e., connected
      component) of interest, which can correspond to objects or voids, and estimating
      the respective medial axes by using a recently proposed wave front propagation
      approach, which is briefly reviewed. The distance values along such axes are
      identified and their mean and standard deviation values obtained. As illustrated
      with respect to synthetic and real objects (in vitro cultures of neuronal cells),
      the combined use of these two features provides a powerful description of the
      uniformity of the separation between the objects, presenting potential for
      several applications in material sciences and biology.

PMID- 14682909
TI  - Determination of effective conductivities of imperfect contact composites with
      first-passage simulation.
AB  - A first-passage simulation scheme is developed to determine the effective
      conductivities of composites with matrix-inclusion interfaces of imperfect
      contact. The necessary mean hitting probabilities and mean scaled traveling times
      of the probing walkers in the close vicinity of the imperfect contact interface
      are derived by solving proposed boundary value problems. The developed scheme is
      first validated through application in the effective conductivity problem of
      composites containing periodically arranged spherical inclusions for which
      accurate results are available for comparison, and is then further applied to the
      effective conductivity problem of composites containing randomly distributed
      spherical inclusions. The present development treats the more general imperfect
      contact problem, with the perfect contact problem as one special case.

PMID- 14682910
TI  - Modified conjugate gradient method for diagonalizing large matrices.
AB  - We present an iterative method to diagonalize large matrices. The basic idea is
      the same as the conjugate gradient (CG) method, i.e, minimizing the Rayleigh
      quotient via its gradient and avoiding reintroducing errors to the directions of
      previous gradients. Each iteration step is to find lowest eigenvector of the
      matrix in a subspace spanned by the current trial vector and the corresponding
      gradient of the Rayleigh quotient, as well as some previous trial vectors. The
      gradient, together with the previous trial vectors, play a similar role as the
      conjugate gradient of the original CG algorithm. Our numeric tests indicate that
      this method converges significantly faster than the original CG method. And the
      computational cost of one iteration step is about the same as the original CG
      method. It is suitable for first principle calculations.

PMID- 14682911
TI  - Potential landscapes and induced charges near metallic islands in three
      dimensions.
AB  - We calculate electrostatic potential landscapes for an external probe charge in
      the presence of a set of metallic islands. Our numerical calculation in three
      dimensions (3D) uses an efficient grid relaxation technique. The well-known
      relaxation algorithm for solving the Poisson equation in two dimensions is
      generalized to 3D. In addition, all charges on the system, free as well as
      induced charges, are determined accurately and self-consistently to satisfy the
      desired boundary conditions. This allows the straightforward calculation of the
      potential on the outer boundary using the free space electrostatic Green's
      function, as well as the calculation of the entire capacitance matrix of the
      system. Physically interesting examples of nanoscale systems are presented and
      analyzed.

PMID- 14682912
TI  - Temporal solitons in quadratic nonlinear media with opposite group-velocity
      dispersions at the fundamental and second harmonics.
AB  - Temporal solitons in quadratic nonlinear media with normal second-harmonic
      dispersion are studied theoretically. The variational approximation and direct
      simulations reveal the existence of soliton solutions, and their stability region
      is identified. Stable solutions are found for large and normal values of the
      second-harmonic dispersion, and in the presence of large group-velocity mismatch
      between the fundamental- and second-harmonic fields. The solitons (or solitonlike
      pulses) are found to have tiny nonlocalized tails in the second-harmonic field,
      for which an analytic exponential estimate is obtained. The estimate and
      numerical calculations show that, in the parameter region of experimental
      relevance, the tails are completely negligible. The results open a way to the
      experimental observation of quadratic solitons with normal second-harmonic
      dispersion, and have strong implication to the experimental search for
      multidimensional "light bullets."

PMID- 14682913
TI  - Comment on "Control of hyperchaos".
AB  - In this Comment we show that the adaptive adjustment mechanism proposed by
      Shouliang, Shaoqing, and Hengqiang [Phys. Rev. E 64, 056212 (2001)] does not
      ensure that the feedback system will converge to the desired orbit as the real
      system is, in general, not known.

PMID- 14682914
TI  - Path coalescence transition and its applications.
AB  - We analyze the motion of a system of particles subjected to a random force
      fluctuating in both space and time, and experiencing viscous damping. When the
      damping exceeds a certain threshold, the system undergoes a phase transition; the
      particle trajectories coalesce. We analyze this transition by mapping it to a
      Kramers problem which we solve exactly. In the limit of weak random force we
      characterize the dynamics by computing the rate at which caustics are crossed,
      and the statistics of the particle density in the coalescing phase. Last but not
      least we describe possible realizations of the effect, ranging from trajectories
      of raindrops on perspex surfaces to animal migration patterns.

PMID- 14682915
TI  - Velocity statistics in two-dimensional granular turbulence.
AB  - We studied the macroscopic statistical properties on the freely evolving
      quasielastic hard disk (granular) system by performing a large-scale (up to a few
      million particles) event-driven molecular dynamics systematically and found it to
      be remarkably analogous to an enstrophy cascade process in the decaying two
      dimensional fluid turbulence. There are four typical stages in the freely
      evolving inelastic hard disk system, which are homogeneous, shearing (vortex),
      clustering, and final state. In the shearing stage, the self-organized
      macroscopic coherent vortices become dominant. In the clustering stage, the
      energy spectra are close to the expectation of Kraichnan-Batchelor theory and the
      squared two-particle separation strictly obeys Richardson law.

PMID- 14682916
TI  - Contribution of the ionic adsorption phenomenon to the effective anchoring energy
      of a nematic liquid-crystal sample.
AB  - The effective anchoring energy resulting from the ionic adsorption phenomenon in
      a nematic liquid-crystal sample in the shape of a slab of thickness d is
      investigated. The electric field distribution is determined in the framework of a
      general nonlinear Poisson-Boltzmann approach. The analysis is particularized for
      the case in which d>>lambdaD, where lambdaD is the Debye screening length. In
      this limit, the spatially dependent electric field distribution across the sample
      as well as the contribution, of dielectric and flexoelectric origins, to the
      effective anchoring energy is obtained in an exact manner.

PMID- 14682917
TI  - Fluctuations of the winding number of a directed polymer in a random medium.
AB  - For a directed polymer in a random medium lying on an infinite cylinder that is
      in 1+1 dimensions with finite width and periodic boundary conditions on the
      transverse direction, the winding number is simply the algebraic number of turns
      the polymer does around the cylinder. This paper presents exact expressions of
      the fluctuations of this winding number due to, first, the thermal noise of the
      system and, second, the different realizations of the disorder in the medium.

PMID- 14682918
TI  - Two-dimensional array of magnetic particles: the role of an interaction cutoff.
AB  - Based on theoretical results and simulations, in two-dimensional arrangements of
      a dense dipolar particle system, there are two relevant local dipole
      arrangements: (1) a ferromagnetic state with dipoles organized in a triangular
      lattice and (2) an antiferromagnetic state with dipoles organized in a square
      lattice. In order to accelerate simulation algorithms, we search for the
      possibility of cutting off the interaction potential. Simulations on a dipolar
      two-line system lead to the observation that the ferromagnetic state is much more
      sensitive to the interaction cutoff R than the corresponding antiferromagnetic
      state. For R approximately > 8 (measured in particle diameters) there is no
      substantial change in the energetical balance of the ferromagnetic and
      antiferromagnetic state and the ferromagnetic state slightly dominates over the
      antiferromagnetic state, while the situation is changed rapidly for lower
      interaction cutoff values, leading to the disappearance of the ferromagnetic
      ground state. We studied the effect of bending ferromagnetic and
      antiferromagnetic two-line systems and observed that the cutoff has a major
      impact on the energetical balance of the ferromagnetic and the antiferromagnetic
      state for R approximately < 4. Based on our results we argue that R approximately
      5 is a reasonable choice for dipole-dipole interaction cutoff in two-dimensional
      dipolar hard sphere systems, if one is interested in local ordering.

PMID- 14682919
TI  - Long range hops and the pair annihilation reaction A+A-->0: renormalization group
      and simulation.
AB  - A simple example of a nonequilibrium system for which fluctuations are important
      is a system of particles which diffuse and may annihilate in pairs on contact.
      The renormalization group can be used to calculate the time dependence of the
      density of particles, and provides both an exact value for the exponent governing
      the decay of particles and an epsilon expansion for the amplitude of this power
      law. When the diffusion is anomalous, as when the particles perform Levy flights,
      the critical dimension depends continuously on the control parameter for the Levy
      distribution. The epsilon expansion can then become an expansion in a small
      parameter. We present the renormalization group calculation and compare these
      results with those of a simulation.

PMID- 14682920
TI  - Fluctuation analysis of stellar x-ray binary systems.
AB  - We study time series of x-ray sources of 129 stellar binary systems present in
      the public data collected by the instrument All Sky Monitor on board of the
      satellite Rossi X-Ray Timing Explorer. The light time series was analyzed by
      applying detrended fluctuation analysis to estimate the long-range power-law
      correlation exponents alpha. The scaling exponent was calculated for all systems
      and its value indicated a signature of each kind of system, i.e., whether flare
      takes place (with alpha=1.22) or not (with alpha=0.64). As a consequence, our
      results may identify the stability of the systems from the scaling exponent alpha
      value, for instance, if alpha approximately 0.5 (white noise) the system is
      stable and unstable when alpha not equal to 0.5 (long-range power-law
      correlation).

PMID- 14682922
TI  - Fluctuations of jamming coverage upon random sequential adsorption on homogeneous
      and heterogeneous media.
AB  - The fluctuations of the jamming coverage upon random sequential adsorption (RSA)
      are studied using both analytical and numerical techniques. Our main result shows
      that these fluctuations (characterized by sigma(thetaJ)) decay with the lattice
      size according to the power law sigma(thetaJ) proportional, variant L(-1/nu). The
      exponent nu depends on the dimensionality D of the substrate and the fractal
      dimension of the set where the RSA process actually takes place (df) according to
      nu=2/(2D-df). This theoretical result is confirmed by means of extensive
      numerical simulations applied to the RSA of dimers on homogeneous and stochastic
      fractal substrates. Furthermore, our predictions are in excellent agreement with
      different previous numerical results. It is also shown that, studying correlated
      stochastic processes, one can define various fluctuating quantities designed to
      capture either the underlying physics of individual processes or that of the
      whole system. So, subtle differences in the definitions may lead to dramatically
      different physical interpretations of the results. Here, this statement is
      demonstrated for the case of RSA of dimers on binary alloys.

PMID- 14682921
TI  - Speed of reaction-diffusion fronts in spatially heterogeneous media.
AB  - The front speed problem for nonuniform reaction rate and diffusion coefficient is
      studied by using singular perturbation analysis, the geometric approach of
      Hamilton-Jacobi dynamics, and the local speed approach. Exact and perturbed
      expressions for the front speed are obtained in the limit of large times. For
      linear and fractal heterogeneities, the analytic results have been compared with
      numerical results exhibiting a good agreement. Finally we reach a general
      expression for the speed of the front in the case of smooth and weak
      heterogeneities.

PMID- 14682923
TI  - Langevin equation for the Rayleigh model with finite-range interactions.
AB  - Both linear and nonlinear Langevin equations are derived directly from the
      Liouville equation for an exactly solvable model consisting of a Brownian
      particle of mass M interacting with ideal gas molecules of mass m via a quadratic
      repulsive potential. Explicit microscopic expressions for all kinetic
      coefficients appearing in these equations are presented. It is shown that the
      range of applicability of the Langevin equation, as well as statistical
      properties of random force, may depend not only on the mass ratio m/M but also on
      the parameter Nm/M, involving the average number N of molecules in the
      interaction zone around the particle. For the case of a short-ranged potential,
      when N<<1, analysis of the Langevin equations yields previously obtained results
      for a hard-wall potential in which only binary collisions are considered. For the
      finite-ranged potential, when multiple collisions are important (N>>1), the model
      describes nontrivial dynamics on time scales that are on the order of the
      collision time, a regime that is usually beyond the scope of more
      phenomenological models.

PMID- 14682924
TI  - Generalizations of the Bruggeman equation and a concept of shape-distributed
      particle composites.
AB  - We consider generalizations of the classical symmetrical Bruggeman equation based
      on the concept of shape-distributed particle systems. The use of the Beta
      distribution for the particle shape is shown to result in some known as well as
      unknown equations of the effective medium theory. However, these equations yield
      no percolation threshold. On the other hand, the use of one- and two-dimensional
      steplike distributions of spheroidal (ellipsoidal) shapes yields a percolation
      threshold depending on the distribution parameters. The problem of finding the
      percolation threshold to fit the systems under consideration, as well as the
      applicability area of the generalized Bruggeman equation and its relation to the
      Bergman representation, are discussed.

PMID- 14682926
TI  - Relationship between dynamical heterogeneities and stretched exponential
      relaxation.
AB  - We identify dynamical heterogeneities as an essential prerequisite for stretched
      exponential relaxation in dynamically frustrated systems. This heterogeneity
      takes the form of ordered domains of finite but diverging lifetime for particles
      in atomic or molecular systems, or spin states in magnetic materials. At the
      onset of the dynamical heterogeneity, the distribution of time intervals spent in
      such domains or traps becomes stretched exponential at long times. We rigorously
      show that once this is the case the autocorrelation function of the renewal
      process formed by these time intervals is also a stretched exponential at long
      times.

PMID- 14682927
TI  - Drift by dichotomous Markov noise.
AB  - We derive explicit results for the asymptotic probability density and drift
      velocity in systems driven by dichotomous Markov noise, including the situation
      in which the asymptotic dynamics crosses unstable fixed points. The results are
      illustrated on the problem of the rocking ratchet.

PMID- 14682925
TI  - Magnetic properties and structure of polydisperse ferrofluid models.
AB  - The influence of polydispersity on the equilibrium properties of dipolar systems
      with short range repulsive interactions (modeled by a shifted and truncated
      Lennard-Jones pair potential) is studied by means of canonical Monte Carlo
      simulation and a high field approximation perturbation theory. The particle
      concentrations and the average magnetic moments of the investigated systems are
      typical of real ferrofluids. The magnetization curves are calculated and the
      microstructures are analyzed as a function of density, and the obtained results
      are compared with the data determined in the monodisperse equivalents of the
      systems. At weak and moderate magnetic fields the magnetization is found to be
      generally higher in the polydisperse system than in the corresponding
      monodisperse one. Our findings for the magnetic properties can partly be
      explained by the structural characteristics obtained from the simulations.

PMID- 14682928
TI  - Quantumlike short-time behavior of a classical crystal.
AB  - We have performed a molecular-dynamics simulation of a face-centered-cubic
      Lennard-Jones crystal, and studied its relaxation toward equilibrium and its
      microcanonical equilibrium dynamics through the computation of the normal modes.
      At low temperature, the weak interaction among normal modes yields a very slow
      relaxation of the fluctuation of the kinetic energy; this requires a new
      formulation of the measure of the microcanonical specific heat at constant
      volume. This specific heat turns out to depend on the time of observation; for
      times of the order of 20 ps, its values are much nearer to the quantum ones than
      to the value 3R predicted by the classical Dulong and Petit law. For longer
      observation times, the classical specific heat progressively approaches 3R over
      most of the temperature range of the solid crystal, with the exception of the
      lowest temperature range, where it still drops to values close to zero. The time
      dependence of the specific heat of the crystal is similar to the behavior found
      in a supercooled liquid near the glass transition.

PMID- 14682929
TI  - Local density fluctuations, hyperuniformity, and order metrics.
AB  - Questions concerning the properties and quantification of density fluctuations in
      point patterns continue to provide many theoretical challenges. The purpose of
      this paper is to characterize certain fundamental aspects of local density
      fluctuations associated with general point patterns in any space dimension d. Our
      specific objectives are to study the variance in the number of points contained
      within a regularly shaped window Omega of arbitrary size, and to further
      illuminate our understanding of hyperuniform systems, i.e., point patterns that
      do not possess infinite-wavelength fluctuations. For large windows, hyperuniform
      systems are characterized by a local variance that grows only as the surface area
      (rather than the volume) of the window. We derive two formulations for the number
      variance: (i) an ensemble-average formulation, which is valid for statistically
      homogeneous systems, and (ii) a volume-average formulation, applicable to a
      single realization of a general point pattern in the large-system limit. The
      ensemble-average formulation (which includes both real-space and Fourier
      representations) enables us to show that a homogeneous point pattern in a
      hyperuniform state is at a "critical point" of a type with appropriate scaling
      laws and critical exponents, but one in which the direct correlation function
      (rather than the pair correlation function) is long ranged. We also prove that
      the non-negativity of the local number variance does not add a new realizability
      condition on the pair correlation. The volume-average formulation is superior for
      certain computational purposes, including optimization studies in which it is
      desired to find the particular point pattern with an extremal or targeted value
      of the variance. We prove that the simple periodic linear array yields the global
      minimum value of the average variance among all infinite one-dimensional
      hyperuniform patterns. We also evaluate the variance for common infinite periodic
      lattices as well as certain nonperiodic point patterns in one, two, and three
      dimensions for spherical windows, enabling us to rank-order the spatial patterns.
      Our results suggest that the local variance may serve as a useful order metric
      for general point patterns. Contrary to the conjecture that the lattices
      associated with the densest packing of congruent spheres have the smallest
      variance regardless of the space dimension, we show that for d=3, the body
      centered cubic lattice has a smaller variance than the face-centered cubic
      lattice. Finally, for certain hyperuniform disordered point patterns, we evaluate
      the direct correlation function, structure factor, and associated critical
      exponents exactly.

PMID- 14682930
TI  - Real space origin of temperature crossovers in supercooled liquids.
AB  - We show that the various crossovers between dynamical regimes observed in
      experiments and simulations of supercooled liquids can be explained in simple
      terms from the existence and statistical properties of dynamical heterogeneities.
      We confirm that dynamic heterogeneity is responsible for the slowing down of
      glass formers at temperatures well above the dynamic singularity Tc predicted by
      mode-coupling theory. Our results imply that activated processes govern the long
      time dynamics even in the temperature regime where they are neglected by mode
      coupling theory. We show that alternative interpretations based on topographic
      properties of the potential energy landscape are inefficient ways of describing
      simple physical features which are naturally accounted for within our approach.
      We show in particular that the reported links between mode coupling and landscape
      singularities do not exist.

PMID- 14682931
TI  - Vortex breakdown control by adding near-axis swirl and temperature gradients.
AB  - Vortex breakdown (VB) is an intriguing effect of practical and fundamental
      interest, occurring, e.g., in tornadoes, above delta-wing aircraft, and in vortex
      devices. Depending on application, VB is either beneficiary or harmful and
      therefore requires a proper control. This study shows that VB can be efficiently
      controlled by a combination of additional near-axis swirl and heat. To explore
      the underlying mechanism, we address a flow in a cylindrical container driven by
      a rotating bottom disk. This model flow has been extensively studied being well
      suited for understanding both the VB mechanism and its control. Our numerical
      analysis explains experimentally observed effects of control corotation and
      counter-rotation (with no temperature gradient) and reveals some flaws of dye
      visualization. An important feature found is that a moderate negative (positive)
      axial gradient of temperature can significantly enforce (diminish) the VB
      enhancement by the counter-rotation. A strong positive temperature gradient
      stimulates the centrifugal instability and time oscillations in the flow with
      counter-rotation. An efficient time-evolution code for axisymmetric compressible
      flows has facilitated the numerical study.

PMID- 14682932
TI  - Correlations and scaling in one-dimensional heat conduction.
AB  - We examine numerically the full spatiotemporal correlation functions for all
      hydrodynamic quantities for the random collision model introduced recently. The
      autocorrelation function of the heat current, through the Kubo formula, gives a
      thermal conductivity exponent of 1/3 in agreement with the analytical prediction
      and previous numerical work. Remarkably, this result depends crucially on the
      choice of boundary conditions: for periodic boundary conditions (as opposed to
      open boundary conditions with heat baths) the exponent is approximately 1/2. All
      primitive hydrodynamic quantities scale with the dynamic critical exponent
      predicted analytically.

PMID- 14682933
TI  - Viscosity in molecular dynamics with periodic boundary conditions.
AB  - We report a study of viscosity by the method of Helfand moment in systems with
      periodic boundary conditions. We propose a new definition of Helfand moment which
      takes into account the minimum image convention used in molecular dynamics with
      periodic boundary conditions. Our Helfand-moment method is equivalent to the
      method based on the Green-Kubo formula and is not affected by ambiguities due to
      the periodic boundary conditions. Moreover, in hard-ball systems, our method is
      equivalent to that developed by Alder, Gass, and Wainwright [J. Chem. Phys. 53,
      3813 (1970)]. We apply and verify our method in a fluid composed of N> or =2 hard
      disks in elastic collisions. We show that the viscosity coefficients already take
      values in good agreement with Enskog's theory for N=2 hard disks in a hexagonal
      geometry.

PMID- 14682934
TI  - Viscosity in the escape-rate formalism.
AB  - We apply the escape-rate formalism to compute the shear viscosity in terms of the
      chaotic properties of the underlying microscopic dynamics. A first-passage
      problem is set up for the escape of the Helfand moment associated with viscosity
      out of an interval delimited by absorbing boundaries. At the microscopic level of
      description, the absorbing boundaries generate a fractal repeller. The fractal
      dimensions of this repeller are directly related to the shear viscosity and the
      Lyapunov exponent, which allows us to compute its values. We apply this method to
      the Bunimovich-Spohn minimal model of viscosity which is composed of two hard
      disks in elastic collision on a torus. These values are in excellent agreement
      with the values obtained by other methods such as the Green-Kubo and Einstein
      Helfand formulas.

PMID- 14682935
TI  - Inertia in the Brazil nut problem.
AB  - The rise dynamics of a large particle, in a granular bed under vertical
      vibrations, is experimentally studied with an inductive device designed to track
      the particle while it climbs through the granulate under different conditions. A
      model based on energy considerations is presented to explain our experimental
      data, drawing the important conclusion that it is the inertia of the particle,
      assisted by Reynolds dilatancy, the driven force behind its ascension mechanism.
      The ascension reveals a friction profile within the column which remains
      unchanged for different accelerations.

PMID- 14682936
TI  - Shear viscosity for a moderately dense granular binary mixture.
AB  - The shear viscosity for a moderately dense granular binary mixture of smooth hard
      spheres undergoing uniform shear flow is determined. The basis for the analysis
      is the Enskog kinetic equation, solved first analytically by the Chapman-Enskog
      method up to first order in the shear rate for unforced systems as well as for
      systems driven by a Gaussian thermostat. As in the elastic case, practical
      evaluation requires a Sonine polynomial approximation. In the leading order, we
      determine the shear viscosity in terms of the control parameters of the problem:
      solid fraction, composition, mass ratio, size ratio, and restitution
      coefficients. Both kinetic and collisional transfer contributions to the shear
      viscosity are considered. To probe the accuracy of the Chapman-Enskog results,
      the Enskog equation is then numerically solved for systems driven by a Gaussian
      thermostat by means of an extension to dense gases of the well-known direct
      simulation Monte Carlo method for dilute gases. The comparison between theory and
      simulation shows, in general, an excellent agreement over a wide region of the
      parameter space.

PMID- 14682937
TI  - Reversible polydisperse parking lot model.
AB  - We use an improved reversible parking lot model to study the compaction of
      vibrated polydisperse media. The particle sizes are distributed according to a
      truncated power law. We introduce a self-consistent desorption mechanism with a
      hierarchical initialization of the system. In this way, we approach densities
      close to unity. The final density depends on the polydispersity of the system as
      well as on the initialization and will reach a maximum value for a certain
      exponent in the power law.

PMID- 14682938
TI  - Pulse dynamics in a chain of granules with friction.
AB  - We study the dynamics of a pulse in a chain of granules with friction. We present
      theories for chains of cylindrical granules (Hertz potential with exponent n=2)
      and of granules with other geometries (n>2). Our results are supported via
      numerical simulations for cylindrical and for spherical granules (n=5/2).

PMID- 14682939
TI  - Structure and magnetic properties of polydisperse ferrofluids: a molecular
      dynamics study.
AB  - We study by Langevin molecular dynamics simulations systematically the influence
      of polydispersity in the particle size, and subsequently in the dipole moment, on
      the physical properties of ferrofluids. The polydispersity is in a first
      approximation modeled by a bidisperse system that consists of small and large
      particles at different ratios of their volume fractions. In the first part of our
      investigations the total volume fraction of the system is fixed, and the volume
      fraction phiL of the large particles is varied. The initial susceptibility chi
      and magnetization curve of the systems show a strong dependence on the value of
      phiL. With the increase of phiL, the magnetization M of the system has a much
      faster increment at weak fields, and thus leads to a larger chi. We performed a
      cluster analysis that indicates that this is due to the aggregation of the large
      particles in the systems. The average size of these clusters increases with
      increasing phiL. In the second part of our investigations, we fixed the volume
      fraction of the large particles, and increased the volume fraction phiS of the
      small particles in order to study their influence on the chain formation of the
      large ones. We found that the average aggregate size formed by large particles
      decreases when phiS is increased, demonstrating a significant effect of the small
      particles on the structural properties of the system. A topological analysis of
      the structure reveals that the majority of the small particles remain
      nonaggregated. Only a small number of them are attracted to the ends of the
      chains formed by large particles.

PMID- 14682940
TI  - Neutron- and light-scattering studies of the liquid-to-glass and glass-to-glass
      transitions in dense copolymer micellar solutions.
AB  - Recent mode coupling theory (MCT) calculations show that if a short-range
      attractive interaction is added to the pure hard sphere system, one may observe a
      new type of glass originating from the clustering effect (the attractive glass)
      as a result of the attractive interaction. This is in addition to the known glass
      forming mechanism due to the cage effect in the hard sphere system (the repulsive
      glass). The calculations also indicate that if the range of attraction is
      sufficiently short compared to the diameter of the particle, within a certain
      interval of volume fractions where the two glass-forming mechanisms nearly
      balance each other, varying the external control parameter, the effective
      temperature, makes the glass-to-liquid-to-glass reentrance and the glass-to-glass
      transitions possible. Here we present experimental evidence of both transitions,
      obtained from small-angle neutron-scattering and photon correlation measurements
      taken from dense L64 copolymer micellar solutions in heavy water. Varying the
      temperature in certain predicted volume fraction range triggers a sharp
      transition between these two different types of glass. In particular, according
      to MCT, there is an end point (called A3 singularity) of this glass-to-glass
      transition line, beyond which the long-time dynamics of the two glasses become
      identical. Our findings confirm this theoretical prediction. Surprisingly,
      although the Debye-Waller factors, the long-time limit of the coherent
      intermediate scattering functions, of these two glasses obtained from photon
      correlation measurements indeed become identical at the predicted volume
      fraction, they exhibit distinctly different intermediate time relaxation.
      Furthermore, our experimental results obtained from volume fractions beyond the
      end point are characterized by the same features as the repulsive glass obtained
      before the end point. A complete phase diagram giving the boundaries of the
      structural arrest transitions for L64 micellar system is given.

PMID- 14682941
TI  - Limit of overheating and the threshold behavior in laser ablation.
AB  - Constant temperature and pressure molecular-dynamics simulations in conjunction
      with constant pressure and enthalpy simulations, designed to examine the
      threshold behavior in laser ablation, demonstrate that the rate of homogeneous
      nucleation (explosive boiling) increases sharply in a very narrow temperature
      range at approximately 90% of the critical temperature. Moreover, the homogeneous
      nucleation is sufficiently rapid to prevent the superheated liquid from entering
      the spinodal region at densities greater than the critical density.

PMID- 14682942
TI  - Very slow relaxation observed in the surface tension of surfactant solutions.
AB  - A light scattering study was made on ripplons generated over the surface of CnTAB
      (n-cetyltrimethyl ammonium bromide) solutions (in the present case n=14 and 16).
      After preparing the sample solution we measured its surface tension for 3 h and
      confirmed that the tension did decrease with time exponentially but very slowly.
      The relaxation time depended on the surfactant concentration of solutions and
      increased sensitively with the progress of dilution, e.g., 3 min at 10(-2) mol/l
      to 80 min at 10(-4) mol/l for C16TAB. The results obtained were correlated with
      surface adsorption densities estimated from the observed surface pressure vs
      concentration curves using Langmuir's adsorption equation. Two mechanisms were
      proposed to interpret such a slow relaxation process: One is a model in which
      reorientation or redistribution of the surfactant molecules adsorbed on the
      solution is considered, while the other is a two-state model that assumes the
      existence of a high energy barrier for surfactant molecules between those on the
      surface and those in the subsurface. A question still remains as to which of the
      two is more probable.

PMID- 14682943
TI  - Microstructure evolution in magnetorheological suspensions governed by Mason
      number.
AB  - The spatiotemporal evolution of field-induced structures in very dilute
      polarizable colloidal suspensions subject to rotating magnetic fields has been
      experimentally studied using video microscopy. We found that there is a crossover
      Mason number (ratio of viscous to magnetic forces) above which the rotation of
      the field prevents the particle aggregation to form chains. Therefore, at these
      high Mason numbers, more isotropic clusters and isolated particles appear. The
      same behavior was also found in recent scattering dichroism experiments developed
      in more concentrated suspensions, which seems to indicate that the dynamics does
      not depend on the volume fraction. Scattering dichroism experiments have been
      used to study the role played by the volume fraction in suspensions with low
      concentration. As expected, we found that the crossover Mason number does not
      depend on the volume fraction. Brownian particle dynamics simulations are also
      reported, showing good agreement with the experiments.

PMID- 14682944
TI  - Thermodynamically consistent fluid particle model for viscoelastic flows.
AB  - A recently proposed viscoelastic dissipative particle dynamics model is put into
      a thermodynamically consistent form that allows for nonisothermal situations.
      This model consists of fluid particles that have an additional elastic vector
      characterizing the state of elongation of the molecules within the fluid
      particle. Very simple physical mechanisms are proposed for the dynamics of the
      elastic vector that, with the help of the GENERIC formalism, allows us to derive
      the full set of dynamic equations for the model. The model is further generalized
      to include polymer diffusion. The connection of the present model with the
      CONNFFESSIT approach and the Brownian configuration field approach is discussed.

PMID- 14682945
TI  - Free energy of liquid water on the basis of quasichemical theory and ab initio
      molecular dynamics.
AB  - We use ab initio molecular dynamics as a basis for quasichemical theory
      evaluation of the free energy of water near conventional liquid thermodynamic
      states. The Perdew-Wang-91 (PW91), Perdew-Burke-Ernzerhof (PBE), and revised PBE
      (rPBE) functionals are employed. The oxygen radial density distribution using the
      rPBE functional is in reasonable agreement with current experiments, whereas the
      PW91 and PBE functionals predict a more structured oxygen radial density
      distribution. The diffusion coefficient with the rPBE functional is in reasonable
      accord with experiments. Using a maximum entropy procedure, we obtain x0 from the
      coordination number distribution xn for oxygen atoms having n neighbors.
      Likewise, we obtain p0 from pn, the probability of observing cavities of
      specified radius containing n water molecules. The probability x0 is a measure of
      the local chemical interactions and is central to the quasichemical theory of
      solutions. The probability p0, central to the theory of liquids, is a measure of
      the free energy required to open cavities of defined sizes in the solvent. Using
      these values and a reasonable model for electrostatic and dispersion effects, the
      hydration free energy of water in water at 314 K is calculated to be -5.1
      kcal/mole with the rPBE functional, in encouraging agreement with the
      experimental value of -6.1 kcal/mole.

PMID- 14682946
TI  - Asymmetric fluid criticality. II. Finite-size scaling for simulations.
AB  - The vapor-liquid critical behavior of intrinsically asymmetric fluids is studied
      in finite systems of linear dimensions L focusing on periodic boundary
      conditions, as appropriate for simulations. The recently propounded "complete"
      thermodynamic (L--> infinity) scaling theory incorporating pressure mixing in the
      scaling fields as well as corrections to scaling [Phys. Rev. E 67, 061506 (2003)]
      is extended to finite L, initially in a grand canonical representation. The
      theory allows for a Yang-Yang anomaly in which, when L--> infinity, the second
      temperature derivative (d2musigma/dT2) of the chemical potential along the phase
      boundary musigmaT diverges when T-->Tc-. The finite-size behavior of various
      special critical loci in the temperature-density or (T,rho) plane, in particular,
      the k-inflection susceptibility loci and the Q-maximal loci--derived from
      QL(T,<rho>L) is identical with <m2>2L/<m4>L where m is identical with rho-<rho>L-
      is carefully elucidated and shown to be of value in estimating Tc and rhoc.
      Concrete illustrations are presented for the hard-core square-well fluid and for
      the restricted primitive model electrolyte including an estimate of the
      correlation exponent nu that confirms Ising-type character. The treatment is
      extended to the canonical representation where further complications appear.

PMID- 14682947
TI  - Interfacial nonequilibrium and Benard-Marangoni instability of a liquid-vapor
      system.
AB  - We study Benard-Marangoni instability in a system formed by a horizontal liquid
      layer and its overlying vapor. The liquid is lying on a hot rigid plate and the
      vapor is bounded by a cold parallel plate. A pump maintains a reduced pressure in
      the vapor layer and evacuates the vapor. This investigation is undertaken within
      the classical quasisteady approximation for both the vapor and the liquid phases.
      The two layers are separated by a deformable interface. Temporarily frozen
      temperature and velocity distributions are employed at each instant for the
      stability analysis, limited to infinitesimal disturbances (linear regime). We use
      irreversible thermodynamics to model the phase change under interfacial
      nonequilibrium. Within this description, the interface appears as a barrier for
      transport of both heat and mass. Hence, in contrast with previous studies, we
      consider the possibility of a temperature jump across the interface, as recently
      measured experimentally. The stability analysis shows that the interfacial
      resistances to heat and mass transfer have a destabilizing influence compared to
      an interface that is in thermodynamic equilibrium. The role of the fluctuations
      in the vapor phase on the onset of instability is discussed. The conditions to
      reduce the system to a one phase model are also established. Finally, the
      influence of the evaporation parameters and of the presence of an inert gas on
      the marginal stability curves is discussed.

PMID- 14682948
TI  - Dynamic transition in etching with poisoning.
AB  - We study a lattice model for etching of a crystalline solid including the
      deposition of a poisoning species. The model considers normal and lateral erosion
      of the columns of the solid by a flux of etching particles and the blocking
      effects of impurities formed at the surface. As the probability p of formation of
      this poisoning species increases, the etching rate decreases and a continuous
      transition to a pinned phase is observed. The transition is in the directed
      percolation (DP) class, with the fraction of the exposed columns as the order
      parameter. This interpretation is consistent with a mapping of the interface
      problem in d+1 dimensions onto a d-dimensional contact process, and is confirmed
      by numerical results in d=1 and d=2. In the etching phase, the interface width
      scales with Kardar-Parisi-Zhang (KPZ) exponents, and shows a crossover from the
      critical DP behavior (W approximately t) to KPZ near the critical point, at
      etching times of the order of (pc-p)(-nu(||)). Anomalous roughening is observed
      at criticality, with the roughness exponent related to DP exponents as
      alphac=nu(||)/nu(perpendicular)>1. The main differences from previously studied
      DP transitions in growth models and isotropic percolation transitions in etching
      models are discussed. Investigations in real systems are suggested.

PMID- 14682949
TI  - Interfaces with a single growth inhomogeneity and anchored boundaries.
AB  - The dynamics of a one-dimensional growth model involving attachment and
      detachment of particles is studied in the presence of a localized growth
      inhomogeneity along with anchored boundary conditions. At large times, the latter
      enforce an equilibrium stationary regime which allows for an exact calculation of
      roughening exponents. The stochastic evolution is related to a spin Hamiltonian
      whose spectrum gap embodies the dynamic scaling exponent of late stages. For
      vanishing gaps the interface can exhibit a slow morphological transition followed
      by a change of scaling regimes which are studied numerically. Instead, a faceting
      dynamics arises for gapful situations.

PMID- 14682950
TI  - Phase-field approach for faceted solidification.
AB  - We extend the phase-field approach to model the solidification of faceted
      materials. Our approach consists of using an approximate gamma plot with rounded
      cusps that can approach arbitrarily closely the true gamma plot with sharp cusps
      that correspond to faceted orientations. The phase-field equations are solved in
      the thin-interface limit with local equilibrium at the solid-liquid interface [A.
      Karma and W.-J. Rappel, Phys. Rev. E 53, R3017 (1996)]. The convergence of our
      approach is first demonstrated for equilibrium shapes. The growth of faceted
      needle crystals in an undercooled melt is then studied as a function of
      undercooling and the cusp amplitude delta for a gamma plot of the form
      gamma=gamma0[1+delta(/sin theta/+/cos theta/)]. The phase-field results are
      consistent with the scaling law Lambda approximately V(-1/2) observed
      experimentally, where Lambda is the facet length and V is the growth rate. In
      addition, the variation of V and Lambda with delta is found to be reasonably well
      predicted by an approximate sharp-interface analytical theory that includes
      capillary effects and assumes circular and parabolic forms for the front and
      trailing rough parts of the needle crystal, respectively.

PMID- 14682951
TI  - Systematic model behavior of adsorption on flat surfaces.
AB  - A low density film on a flat surface is described by an expansion involving the
      first four virial coefficients. The first coefficient (alone) yields the Henry's
      law regime, while the next three terms in the expansion correct for the effects
      of adsorbate-adsorbate interactions, computed within the two-dimensional
      approximation (a film confined nearly to a plane). The results permit exploration
      of the idea of universal adsorption behavior, which is compared with experimental
      data for a number of systems. The idea works well, in general, justifying a
      general model of adsorption at low to moderate coverage.

PMID- 14682952
TI  - Wetting under nonequilibrium conditions.
AB  - We report a detailed account of the phase diagram of a recently introduced model
      for nonequilibrium wetting in (1+1) dimensions [H. Hinrichsen, R. Livi, D.
      Mukamel, and A. Politi, Phys. Rev. Lett. 79, 2710 (1997)]. A mean-field
      approximation is shown to reproduce the main features of the phase diagram, while
      providing indications for the behavior of the wetting transition in higher
      dimensions. The mean-field phase diagram is found to exhibit an extra transition
      line which does not exist in (1+1) dimensions. The line separates a phase in
      which the interface height distribution decays exponentially at large heights
      from a superexponentially decaying phase. Implications to wetting in dimensions
      higher than (1+1) are discussed.

PMID- 14682953
TI  - Convective instabilities in two superposed horizontal liquid layers heated
      laterally.
AB  - This work is devoted to the theoretical study of the stability of two superposed
      horizontal liquid layers bounded by two solid planes and subjected to a
      horizontal temperature gradient. The liquids are supposed to be immiscible with a
      nondeformable interface. The forces acting on the system are buoyancy and
      interfacial tension. Four different flow patterns and temperature profiles are
      found for the basic state. A linear perturbative analysis with respect to two-
      and three-dimensional perturbations reveals the existence of three kinds of
      patterns. Depending on the relative height of both liquids several situations are
      predicted: either wave propagation from cold to the hot regions, or waves
      propagating in the opposite direction or still stationary longitudinal rolls. The
      behavior of three different pairs of liquids which have been used in experiments
      on bilayers under vertical gradient by other authors have been examined. The
      instability mechanisms are discussed and a qualitative interpretation of the
      different behaviors exhibited by the system is provided. In some configurations
      it is possible to find a codimension-two point created by the interaction of two
      Hopf modes with different frequencies and wave numbers. These results suggest to
      consider two liquid layers as an interesting prototype for the study of
      propagation and interaction of waves in the context of the Benard-Marangoni
      problem.

PMID- 14682954
TI  - Transition from Knudsen to molecular diffusion in activity of absorbing irregular
      interfaces.
AB  - We investigate through molecular dynamics the transition from Knudsen to
      molecular diffusion transport towards two-dimensional absorbing interfaces with
      irregular geometry. Our results indicate that the length of the active zone
      decreases continuously with density from the Knudsen to the molecular diffusion
      regime. In the limit where molecular diffusion dominates, we find that this
      length approaches a constant value of the order of the system size, in agreement
      with theoretical predictions for Laplacian transport in irregular geometries.
      Finally, we show that all these features can be qualitatively described in terms
      of a simple random-walk model of the diffusion process.

PMID- 14682955
TI  - Hexatic-herringbone coupling at the hexatic transition in smectic liquid
      crystals: 4-epsilon renormalization group calculations revisited.
AB  - Simple symmetry considerations would suggest that the transition from the smectic
      A phase to the long-range bond-orientationally ordered hexatic smectic-B phase
      should belong to the XY universality class. However, a number of experimental
      studies have reported over the past twenty years "novel" critical behavior with
      non-XY critical exponents for this transition. Bruinsma and Aeppli argued [Phys.
      Rev. Lett. 48, 1625 (1982)], using a 4-epsilon renormalization-group calculation,
      that short-range molecular herringbone correlations coupled to the hexatic
      ordering drive this transition first order via thermal fluctuations, and that the
      critical behavior observed in real systems is controlled by a "nearby"
      tricritical point. We have revisited the model of Bruinsma and Aeppli and present
      here the results of our study. We have found two nontrivial strongly coupled
      herringbone-hexatic fixed points apparently missed by these authors. Yet, these
      two nontrivial fixed points are unstable, and we obtain the same final conclusion
      as the one reached by Bruinsma and Aeppli, namely that of a fluctuation-driven
      first-order transition. We also discuss the effect of local twofold distortion of
      the bond order as a possible "extra" order parameter in the Hamiltonian.

PMID- 14682956
TI  - Simulations of helix unwinding in ferroelectric liquid crystals.
AB  - In bulk ferroelectric liquid crystals, the molecular director twists in a helix.
      In narrow cells, this helix can be unwound by an applied electric field or by
      boundary effects. To describe helix unwinding as a function of both electric
      field and boundary effects, we develop a mesoscale simulation model based on a
      continuum free energy discretized on a two-dimensional lattice. In these
      simulations, we determine both the director profile across the cell and the net
      electrostatic polarization. By varying the cell size, we show how boundary
      effects shift the critical field for helix unwinding and lower the saturation
      polarization. Our results are consistent with experimental data.

PMID- 14682957
TI  - Smectic blue phases: layered systems with high intrinsic curvature.
AB  - We report on a construction for smectic blue phases, which have quasi-long-range
      smectic translational order as well as three-dimensional crystalline order. Our
      proposed structures fill space by adding layers on top of a minimal surface,
      introducing either curvature or edge defects as necessary. We find that for the
      right range of material parameters, the favorable saddle-splay energy of these
      structures can stabilize them against uniform layered structures. We also
      consider the nature of curvature frustration between mean curvature and saddle
      splay.

PMID- 14682958
TI  - Optical studies of the nematic phase of an oxazole-derived bent-core liquid
      crystal.
AB  - Various optical and dynamic light scattering studies have been conducted on the
      nematic phase of an oxazole-derived bent-core liquid crystal. At optical length
      scales and in the absence of applied fields, homogeneously aligned samples of
      this material, which has an oxazole heterocyclic ring in the central core, are
      found to behave more like a conventional straight-core nematic than a previously
      investigated ester-based class of bent-core molecules that have a benzene ring as
      the core linkage between the two arms of the bow-shaped molecule. In particular,
      the nematic refractive indices of the oxazole compound combine in the standard
      way [i.e., square root of ((2no2+ne2)/3)] to match the isotropic value throughout
      the nematic range, and the observed director fluctuation modes have relaxation
      rates comparable to those of the usual thermotropics. However, polarized light
      scattering data reveal evidence of weak biaxial fluctuations, and indications of
      electric-field-induced biaxiality are observed in the refractive index
      measurements.

PMID- 14682959
TI  - NMR proton spin dynamics in thermotropic liquid crystals subject to multipulse
      excitation.
AB  - Previous experiments of NMR spin-lattice relaxation times as a function of the
      Larmor frequency, as measured with the field-cycling technique (FC), were shown
      to be very useful to disentangle the various molecular motions, both local and
      collective, that dominate the relaxation in different time scales in liquid
      crystals. However, there are many examples where the known theoretical models
      that represent the molecular relaxation mechanisms cannot be fitted to the
      experimental trend in the region of low fields, making it difficult to obtain
      reliable values for the spectral densities involved, especially for the
      cooperative motions which dominate at low frequencies. In some cases, these
      anomalies are loosely ascribed to "local-field" effects but, to our knowledge,
      there is not a detailed explanation about the origin of these problems nor the
      range of frequencies where they should be expected. With the aim of isolating the
      dipolar effects from the influence of molecular dynamics, and taking into account
      the previous results in solids, in this work we investigate the response of the
      proton spin system of thermotropic liquid crystals 4-pentyl-4'-cyanobiphenyl
      (5CB) and 4-octyl-4'-cyanobiphenyl (8CB) in nematic and smectic A phases, due to
      the NMR multipulse sequence 90( composite function )y-(tau-thetax-tau)N. The
      nuclear magnetization presents an early transient period characterized by strong
      oscillations, after which a quasistationary state is attained. Subsequently, this
      state relaxes towards internal equilibrium over a time much longer than the
      transverse relaxation time T2. As occurs in solids, the decay time of the
      quasistationary state T2e presents a minimum when the pulse width thetax and the
      offset of the radiofrequency are set to satisfy resonance conditions (spin-lock).
      When measured as a function of the pulse spacing tau in "on-resonance"
      experiments, T2e shows the behavior expected for cross relaxation between the
      effective Zeeman and dipolar reservoirs, in accordance with the thermodynamic
      theory previously developed for solids. Particularly, for values of tau
      comparable with T2, the relaxation rate follows a power law T2e proportional to
      tau(-2), in all the observed cases, for the resonance conditions thetax=pi/3 and
      equivalent frequency omegae=pi/3tau. When tau is similar to or greater than
      typical dipolar periods, the relaxation rate becomes constant and for tau much
      shorter than T2, the thermodynamic reservoirs get decoupled. These experiments
      confirm that the thermodynamic picture is valid also in liquid crystals and the
      cross relaxation between the reservoirs can be detected without interference with
      spin-lattice relaxation effects. Accordingly, this technique can be used to
      estimate the frequency range, where cross-relaxation effects can be expected when
      Zeeman and dipolar reservoirs are put in thermal contact with each other and with
      the lattice, as in FC experiments. In particular, the present results allow us to
      associate the anomalies observed in low-field spin-lattice relaxation with
      nonadiabatic energy exchange between the reservoirs.

PMID- 14682960
TI  - Hydrodynamics of isotropic ferrogels.
AB  - We derive the complete set of macroscopic dynamic equations for ferrogels under
      an external magnetic field, including the magnetization as an independent dynamic
      degree of freedom. The magnetoelasticity comes in the form of magnetostriction
      and through the magnetic part of the Maxwell stress. Various dynamic couplings of
      the elastic degree of freedom with the magnetization and the magnetic field are
      found. We discuss static elongation, shear deformations, and the modified sound
      spectrum in the presence of an external magnetic field.

PMID- 14682961
TI  - Absorption effects in liquid crystal waveguides.
AB  - An analytical and numerical study of the propagation of optical fields through a
      nematic hybrid slab is developed. We take into account explicitly the absorption
      of radiation by the liquid crystal by introducing a complex dielectric tensor.
      For a low intensity beam we first derive the eikonal equation and from it we
      calculate the ray trajectories in the optical limit. We show that in the presence
      of absorption, there are no caustics within the slab. Then we consider the WKB
      limit and calculate the field transverse magnetic modes, their number and their
      cutoff frequencies. We show that for both limits the agreement between our
      analytical and numerical results for the propagation constants is excellent,
      while there are larger differences in the analytically and numerically calculated
      field amplitudes. These differences show that absorption effects are important
      for this quantity and have their origin in the fact that the chosen parameter
      values in our exact numerical calculations, strictly speaking, do not lie within
      the limits of validity of the WKB approximation. Although a more precise
      comparison between these approaches requires the use of different sets of values
      of the relevant parameters, our analysis shows the effects and complications
      arising from the inclusion of absorption. Finally, we discuss the scope and
      limitations of our approach.

PMID- 14682962
TI  - Thermal and optical study of the kinetics of the nematic-isotropic transition in
      octylcyanobiphenyl.
AB  - It is shown in this paper that the kinetics of the nematic-isotropic (NI)
      transition in 30-microm-thick octylcyanobiphenyl liquid crystal films is strongly
      affected by the cell walls. We have found that this is due to the modification of
      the wetting properties of the liquid crystal depending on the surface treatment.
      The results have been obtained with an experimental setup which allows the
      simultaneous high resolution study of the sample thermal properties and texture
      evolution with temperature. An accurate determination of the width of the two
      phase coexistence region associated with the NI transition has been possible and
      it is shown that it is affected by the presence of a surfactant. The results have
      been interpreted with a simple model which is based on the possible presence of a
      well-defined interface between the nematic and the isotropic phases in the
      coexistence region, which depends not only on the thermal gradients in the sample
      but also on the surface treatments.

PMID- 14682963
TI  - External and intrinsic anchoring in nematic liquid crystals: a Monte Carlo study.
AB  - We present a Monte Carlo study of external surface anchoring in nematic cells
      with partially disordered solid substrates, as well as of intrinsic anchoring at
      free nematic interfaces. The simulations are based on the simple hexagonal
      lattice model with a spatially anisotropic intermolecular potential. We estimate
      the corresponding extrapolation length b by imposing an elastic deformation in a
      hybrid cell-like nematic sample. Our estimates for b increase with increasing
      surface disorder and are essentially temperature independent. Experimental values
      of b are approached only when both the coupling of nematic molecules with the
      substrate and the anisotropy of nematic-nematic interactions are weak.

PMID- 14682964
TI  - Blue phases induced by doping chiral nematic liquid crystals with nonchiral
      molecules.
AB  - The emergence of the blue phases I and II that are thought to exist in highly
      chiral systems has been found in chiral nematic liquid crystals (N* LCs) when
      they are doped with achiral bent-core liquid crystals (banana mesogens). The same
      effect was also observed by adding racemic 4-(1-methylheptyl oxycarbonyl)phenyl
      4'-octyloxybiphenyl-4-carboxylate (MHPOBC), while achiral terephthal-bis(p
      butylaniline) (TBBA) was not effective. The difference was attributed to the
      different conformations, i.e., MHPOBC is known to have a bent shape, but not
      TBBA. The doping effect is more remarkable in N* LCs with higher chiral content
      for both banana mesogens and MHPOBC. This unusual doping effect was attributed to
      selective chiral interaction between the chiral conformers of guest molecules and
      chiral host molecules and/or the decrease of the surface elastic constant on
      adding bent-shaped guest molecules.

PMID- 14682965
TI  - Dynamics of polymer chain collapse into compact states.
AB  - Molecular dynamics simulation methods are used to study the folding of polymer
      chains into packed cubic states. The polymer model, based on a chain of linked
      sites moving in the continuum, includes both excluded volume and torsional
      interactions. Different native-state packing arrangements and chain lengths are
      explored; the organization of the native state is found to affect both the
      ability of the chain to fold successfully and the nature of the folding pathway
      as the system is gradually cooled. An order parameter based on contact counts is
      used to provide information about the folding process, with contacts additionally
      classified according to criteria such as core and surface sites or local and
      distant site pairs. Fully detailed contact maps and their evolution are also
      examined.

PMID- 14682966
TI  - Validity of the scaling functional approach for polymer interfaces as a
      variational theory.
AB  - We discuss the soundness of the scaling functional (SF) approach proposed by
      Aubouy Guiselin and Raphael [Macromolecules 29, 7261 (1996)] to describe
      polymeric interfaces. In particular, we demonstrate that this approach is a
      variational theory. We emphasize the role of SF theory as an important link
      between ground-state theories suitable to describe adsorbed layers, and
      "classical" theories for polymer brushes.

PMID- 14682967
TI  - Food-web based unified model of macro- and microevolution.
AB  - We incorporate the generic hierarchical architecture of foodwebs into a "unified"
      model that describes both micro- and macroevolutions within a single theoretical
      framework. This model describes the microevolution in detail by accounting for
      the birth, ageing, and natural death of individual organisms as well as prey
      predator interactions on a hierarchical dynamic food web. It also provides a
      natural description of random mutations and speciation (origination) of species
      as well as their extinctions. The distribution of lifetimes of species follows an
      approximate power law only over a limited regime.

PMID- 14682968
TI  - Hofmeister effects in membrane biology: the role of ionic dispersion potentials.
AB  - Membrane biology is notorious for its remarkable, and often strong dependence on
      the supposedly irrelevant choice of ion pair of background salt solution. While
      experimentally well known, there has been no progress towards any real
      theoretical understanding until very recently. We have demonstrated that an
      important source behind these Hofmeister effects is the ionic excess
      polarizabilities of ions in solution. Near an interface an ion experiences not
      only an electrostatic potential, but also a highly specific ionic dispersion
      potential. At biological concentrations (around 0.1 M and higher) when the
      electrostatic contribution is highly screened this ionic dispersion potential has
      a dominating influence. We present the result of model calculations for the
      interfacial tension and surface potential that demonstrates that inclusion of
      ionic dispersion potentials is an essential step towards predictive theories. Our
      results are compared with experimental surface and zeta potential measurements on
      phospholipid bilayers, zirconia, and cationic micelles.

PMID- 14682969
TI  - Speciation in multidimensional evolutionary space.
AB  - Adaptive dynamics in two-dimensional phenotype space is investigated by computer
      simulation. The model assumes Lotka-Voltera-type competition and a stochastic
      mutation process. The carrying capacity has a single maximum in the origin of the
      strategy space and the competition coefficient decreases with strategy
      difference. Evolutionary branching, an asexual analog of adaptive speciation, is
      observed with suitable parameters. The branching at the singular point, which is
      a fixed point of the directional evolution, may occur into two or three, but not
      more, directions. Further branchings may occur after the initial separation. The
      probability of three-branching is studied as a function of several parameters. We
      conclude that the two-way branching is the predominant mode of adaptive
      speciation.

PMID- 14682970
TI  - Statistical mechanics of RNA folding: importance of alphabet size.
AB  - We construct a base-stacking model of RNA secondary-structure formation and use
      it to study the mapping from sequence to structure. There are strong, qualitative
      differences between two-letter and four- or six-letter alphabets. With only two
      kinds of bases, most sequences have many alternative folding configurations and
      are consequently thermally unstable. Stable ground states are found only for a
      small set of structures of high designability, i.e., total number of associated
      sequences. In contrast, sequences made from four bases, as found in nature, or
      six bases have far fewer competing folding configurations, resulting in a much
      greater average stability of the ground state.

PMID- 14682971
TI  - Existence of high-order correlations in cortical activity.
AB  - Neurons collect signals originating from a large number of other cells. The
      variability of this integrated population activity at the millisecond time scale
      is a critical constraint on the degree of signal integration and processing
      performed by single neurons. Optical imaging, EEG, and fMRI studies have
      indicated that cortical activity shows a high degree of variability at a time
      scale of hundreds of ms. However, currently no experimental methods are available
      to directly assess the variability in the activity of populations of neurons at a
      time scale closer to that of the characteristic time constants of neurons, i.e.,
      around 10 ms. Here we integrate pertinent experimental data in one rigorous
      mathematical framework to demonstrate that (1) the high temporal variability in
      the spiking activity of individual neurons, (2) the second-order correlation
      properties of the spiking activity of cortical neurons, and (3) the correlations
      of the subthreshold dynamics, all impose high amplitude, fast variability in the
      population activity of cortical neurons. This implies that higher order
      correlations, a necessary condition for temporal coding models, must be a central
      feature of cortical dynamics.

PMID- 14682972
TI  - Measurements and modeling of water transport and osmoregulation in a single
      kidney cell using optical tweezers and videomicroscopy.
AB  - With an optical tweezer installed in our optical microscope we grab a single
      Madin Darby Canine kidney cell and keep it suspended in the medium without
      touching the glass substrate or other cells. Since the optically trapped cell
      remains with a closely round shape, we can directly measure its volume by using
      videomicroscopy with digital image analysis. We submit this cell to a
      hyperosmotic shock (up-shock) and video record the process: the cell initially
      shrinks due to osmotic efflux of water and after a while, due to regulatory
      volume increase (RVI), an osmoregulation response, it inflates again (water
      influx) until it reaches a new volume (the regulatory volume VR). In addition to
      considering standard osmotic water transport, we model RVI using a simple
      phenomenological model. We obtain an expression for cell volume variation as a
      function of time that fits very well with our experimental data, where two
      characteristic times appear naturally: one related to water transport and the
      other related to RVI. From the fit we obtain water permeability, osmolyte influx
      rate for RVI, and regulatory volume. With the addition of the hormone
      vasopressin, water permeability increases while the regulatory volume decreases
      until inhibition of RVI. In summary, we present a technique to measure directly
      volume changes of a single isolated kidney cell under osmotic shock and a
      phenomenological analysis of water transport that takes into account
      osmoregulation.

PMID- 14682973
TI  - Finite-size thermomechanical effects in smectic liquid crystals: The vapor
      pressure paradox as an anharmonic phenomenon.
AB  - We pursue a systematic statistical mechanics study of finite smectic stacks of
      semiflexible manifolds bounded by interfaces under tension. We address, by
      analytic calculations and Monte Carlo simulations, the effects of the surface
      tension on smectic interlayer distances. We use our theoretical results to
      elucidate the so called vapor pressure paradox (VPP) in multilamellar membrane
      phases and explain the experiments of Katsaras [Biophys. J. 73, 2924 (1997); 75,
      2157 (1998)]. We show that the effects of the interfacial tension are
      substantially weaker than suggested by the previous theoretical discussion of the
      VPP effects [R. Podgornik and V. A. Parsegian, Biophys. J. 72, 942 (1997)]. By
      consistently taking into account the discrete, layered character of smectic
      liquid crystals, and anharmonic phonon effects, we show that the essence of VPP
      effects is in spatially nonuniform thermal expansion of smectic interlayer
      separations. We find that the average period of the whole finite stack can be
      both smaller (ordinary VPP effect at high enough interfacial tensions) or bigger
      (a reverse VPP effect at low interfacial tensions, overlooked in previous
      studies), relative to the average period of the corresponding infinite smectic
      stack. Looking at stacks from outside, these two effects show up as if there is
      an attractive (for the ordinary VPP effect), or repulsive (for the reverse VPP
      effect) pseudo-Casimir force acting between the two stack interfaces. We show
      however that the physics of VPP effects is obscured by schematically invoking
      Casimir-like forces. Rather, the ordinary and the reverse VPP effects are to be
      both characterized as thermomechanical anharmonic effects caused by a spatially
      nonuniform thermal expansion of smectic interlayer distances. Interlayer
      distances close to stack surfaces expand less (more) for the ordinary (reverse)
      VPP effect than those deep in the stack. The reverse VPP prevails at low
      interfacial tensions, simply because the membrane at the top of the stack is more
      free to fluctuate than membranes in the bulk. By increasing interfacial tension
      above a threshold value, fluctuations of the membrane at the stack top become
      suppressed, and the ordinary VPP effect prevails. In this study, we demonstrate
      that finite-size VPP effects in a strongly entropic system, such as the
      sterically stabilized lamellar phases, can be described quantitatively well by a
      simple analytic approach.

PMID- 14682974
TI  - Experimental support for a model of birdsong production.
AB  - In this work we present an experimental validation of a recently proposed model
      for the production of birdsongs. We have previously observed that driving the
      model with simple functions of time, which represent tensions in vocal muscles,
      produces a wide variety of sounds resembling birdsongs. In this work we drive the
      model with functions whose time dependence comes from recordings of muscle
      activities and air sac pressure. We simultaneously recorded the birds' songs and
      compared them with the synthetic songs. The model produces recognizable songs.
      Beyond finding a qualitative agreement, we also test some predictions of the
      model concerning the relative levels of activity in the gating muscles at the
      beginning and end of a syllable.

PMID- 14682975
TI  - Dynamical mean-field theory of noisy spiking neuron ensembles: application to the
      Hodgkin-Huxley model.
AB  - A dynamical mean-field approximation (DMA) previously proposed by the present
      author [H. Hasegawa, Phys. Rev E 67, 041903 (2003)] has been extended to
      ensembles described by a general noisy spiking neuron model. Ensembles of N-unit
      neurons, each of which is expressed by coupled K-dimensional differential
      equations (DEs), are assumed to be subject to spatially correlated white noises.
      The original KN-dimensional stochastic DEs have been replaced by K(K+2)
      dimensional deterministic DEs expressed in terms of means and the second-order
      moments of local and global variables: the fourth-order contributions are taken
      into account by the Gaussian decoupling approximation. Our DMA has been applied
      to an ensemble of Hodgkin-Huxley (HH) neurons (K=4), for which effects of the
      noise, the coupling strength, and the ensemble size on the response to a single
      spike input have been investigated. Numerical results calculated by the DMA
      theory are in good agreement with those obtained by direct simulations, although
      the former computation is about a thousand times faster than the latter for a
      typical HH neuron ensemble with N=100.

PMID- 14682976
TI  - Single stranded DNA translocation through a nanopore: a master equation approach.
AB  - We study voltage driven translocation of a single stranded DNA through a membrane
      channel. Our model, based on a master equation approach, investigates the
      probability density function of the translocation times, and shows that it can be
      either double peaked or mono peaked, depending on the system parameters. We show
      that the most probable translocation time is proportional to the polymer length,
      and inversely proportional to the first or second power of the voltage, depending
      on the initial conditions. The model recovers experimental observations on
      hetropolymers when using their properties inside the pore, such as stiffness and
      polymer-pore interaction.

PMID- 14682977
TI  - Helix versus sheet formation in a small peptide.
AB  - Segments with the amino acid sequence EKAYLRT (glutamine-lysine-alanine-tyrosine
      leucine-arginine-threonine) appear in naturally occurring proteins both in alpha
      helices and beta-sheets. For this reason, we have used this peptide to study how
      secondary structure formation in proteins depends on the local environment. Our
      data rely on multicanonical Monte Carlo simulations where the interactions among
      all atoms are taken into account. Results in gas phase are compared with that in
      an implicit solvent. We find that both the solvated molecule and EKAYLRT in gas
      phase form an alpha-helix when not interacting with other molecules. However, in
      the vicinity of a beta-strand, the peptide forms a beta-strand. Because of this
      change in secondary structure our peptide may provide a simple model for the
      alpha-->beta transition that is supposedly related to the outbreak of prion
      diseases and similar illnesses.

PMID- 14682978
TI  - Generating neural circuits that implement probabilistic reasoning.
AB  - We extend the hypothesis that neuronal populations represent and process analog
      variables in terms of probability density functions (PDFs). Aided by an
      intermediate representation of the probability density based on orthogonal
      functions spanning an underlying low-dimensional function space, it is shown how
      neural circuits may be generated from Bayesian belief networks. The ideas and the
      formalism of this PDF approach are illustrated and tested with several elementary
      examples, and in particular through a problem in which model-driven top-down
      information flow influences the processing of bottom-up sensory input.

PMID- 14682979
TI  - Synchronization between main rhythmic processes in the human cardiovascular
      system.
AB  - For the cases of spontaneous respiration and paced respiration with a fixed
      frequency and linearly increasing frequency, we investigate synchronization
      between three main rhythmic processes governing the cardiovascular dynamics in
      humans, namely, the main heart rhythm, respiration, and the process whose
      fundamental frequency is close to 0.1 Hz. The analysis of the experimental
      records reveals synchronous regimes of different orders n:m between all the three
      main rhythms. The influence of the regime of breathing and the magnitude of heart
      rate variability on the degree of synchronization is considered.

PMID- 14682980
TI  - Time scale and other invariants of integrative mechanical behavior in living
      cells.
AB  - In dealing with systems as complex as the cytoskeleton, we need organizing
      principles or, short of that, an empirical framework into which these systems
      fit. We report here unexpected invariants of cytoskeletal behavior that comprise
      such an empirical framework. We measured elastic and frictional moduli of a
      variety of cell types over a wide range of time scales and using a variety of
      biological interventions. In all instances elastic stresses dominated at
      frequencies below 300 Hz, increased only weakly with frequency, and followed a
      power law; no characteristic time scale was evident. Frictional stresses
      paralleled the elastic behavior at frequencies below 10 Hz but approached a
      Newtonian viscous behavior at higher frequencies. Surprisingly, all data could be
      collapsed onto master curves, the existence of which implies that elastic and
      frictional stresses share a common underlying mechanism. Taken together, these
      findings define an unanticipated integrative framework for studying protein
      interactions within the complex microenvironment of the cell body, and appear to
      set limits on what can be predicted about integrated mechanical behavior of the
      matrix based solely on cytoskeletal constituents considered in isolation.
      Moreover, these observations are consistent with the hypothesis that the
      cytoskeleton of the living cell behaves as a soft glassy material, wherein
      cytoskeletal proteins modulate cell mechanical properties mainly by changing an
      effective temperature of the cytoskeletal matrix. If so, then the effective
      temperature becomes an easily quantified determinant of the ability of the
      cytoskeleton to deform, flow, and reorganize.

PMID- 14682981
TI  - Evaluation of entrainment of a nonlinear neural oscillator to white noise.
AB  - The Lyapunov exponent for a one-dimensional neural oscillator model, the theta
      neuron, is computed for white noise forcing, using the steady-state solution to
      the associated Fokker-Planck equation. The latter is mildly singular, due to the
      nature of the multiplicative input. In agreement with previous results with
      similar models, the exponent is negative for all forcing amplitudes, but here it
      is shown to be small, relative to that for periodic drive, in a range of forcing
      strengths. Thus the synchronization of an ensemble of independent neurons
      receiving common but random input can be slow. Moreover, this implies that
      aperiodic input may be suboptimal, in some contexts, for preserving the
      reliability of fine spike timing, a potentially important component of the neural
      "code."

PMID- 14682982
TI  - Adiabatic heating and convection caused by a fixed-heat-flux source in a near
      critical fluid.
AB  - Dynamics and heat transfer in a near-critical fluid in a square cavity with a
      finite heat source located at the bottom are studied numerically. A thermally
      insulated enclosure and a fixed-heat-flux source are considered. The two
      dimensional simulation is based on the full Navier-Stokes equations with two
      scale splitting of the pressure and the van der Waals equation of state. It is
      shown that the piston effect is independent of convection. Near the critical
      point, this effect becomes independent of criticality and convective motions are
      damped.

PMID- 14682983
TI  - Microdisplacements induced by a local perturbation inside a granular packing.
AB  - The microdisplacements generated by a small localized overload at the free
      surface are visualized experimentally inside a packing of steel beads. For a
      triangular packing, beads rearrangements remain confined in two inverted
      triangles on both sides of the applied overload. This pattern disappears for
      stronger disorder. A simple model allows us to account for these observations and
      to relate them to the stress function response measured via photoelastic
      visualizations. This provides a different tool to probe the mechanical Green's
      function in weakly confined packings of rigid grains the description of which is
      the most challenged.

PMID- 14682984
TI  - Particle interactions near the contact line in liquid drops.
AB  - Micrometer-sized particles distributed in a drop of water are drawn toward the
      contact line upon evaporation, where they arrange themselves into a crystal
      structure. Here we report experiments with paramagnetic particles, which make it
      possible to measure the particle interactions by tuning an external magnetic
      field. By aligning the magnetic dipoles, we are also able to redistribute the
      particles back into the bulk of the droplet. This method allows us to assemble
      and disassemble colloidal crystals simply by applying a magnetic field.

PMID- 14682985
TI  - Nonlinear dynamics in laser polarization conversion by stimulated scattering in
      nematic liquid crystal films.
AB  - We present a study of the nonlinear dynamics of a coherent polarization
      conversion process in nematic liquid crystal films. This effect is mediated by
      two-beam coupling between the incident polarized laser and its orthogonally
      polarized (lower-frequency) noise component scattered by the director axis
      fluctuations. A complete model for the director dynamics derived from the basic
      equations is presented. The existence of complex, time-, and intensity-dependent
      dynamics of the director motion such as oscillations and various bifurcations
      including period doubling is revealed.

PMID- 14682986
TI  - Electroconvection in nematic liquid crystals in Hele-Shaw cells.
AB  - We report electrohydrodynamic instability in nematic liquid crystals found in
      Hele-Shaw cells. Due to the present cell geometry, the convective structures
      could be directly visualized as surface or bulk flows. An unexpected structure is
      observed, which is completely different from the well-known patterns in the
      standard cells. By using the voltage-frequency jump method, the stability of a
      convective structure in Hele-Shaw cells is discussed in terms of the Busse
      diagram.

PMID- 14682987
TI  - Survival probability of a ballistic tracer particle in the presence of diffusing
      traps.
AB  - We calculate the survival probability P(S)(t) up to time t of a tracer particle
      moving along a deterministic trajectory in a continuous d-dimensional space in
      the presence of diffusing but mutually noninteracting traps. In particular, for a
      tracer particle moving ballistically with a constant velocity c, we obtain an
      exact expression for P(S)(t), valid for all t, for d<2. For d> or =2, we obtain
      the leading asymptotic behavior of P(S)(t) for large t. In all cases, P(S)(t)
      decays exponentially for large t, P(S)(t) approximately exp(-theta t). We provide
      an explicit exact expression for the exponent theta in dimensions d< or =2 and
      for the physically relevant case, d=3, as a function of the system parameters.

PMID- 14682989
TI  - Dynamic force spectroscopy: optimized data analysis.
AB  - The forced rupture of single chemical bonds in biomolecular compounds (e.g.,
      ligand-receptor systems) as observed in dynamic force spectroscopy experiments is
      addressed. An optimized method of data analysis is proposed. This method
      significantly outperforms the current standard one when applied to data from an
      idealized numerical computer simulation of an experiment with realistic parameter
      values. In particular, the force-free dissociation rate can be inferred with a
      considerably smaller statistical uncertainty and without the systematic
      overestimation of about 30%, which is shown to be inherent in the standard
      method.

PMID- 14682988
TI  - Coupling-induced oscillations in overdamped bistable systems.
AB  - It is well known that overdamped and unforced dynamical systems do not oscillate.
      However, well-designed coupling schemes, together with the appropriate choice of
      initial conditions, can induce oscillations when a control parameter exceeds a
      threshold value. We demonstrate this effect in a specific system, a soft
      potential mean-field description of the dynamics in a (hysteretic) single-domain
      ferromagnetic sample. Using a specific (unidirectional, with cyclic boundary
      conditions) coupling scheme, together with nonidentical initial conditions, one
      can cause the coupled system of N elements (N odd) to oscillate when the coupling
      coefficient is swept through a critical value. The ensuing oscillations could
      find utility in the detection of very weak "target" signals, via their effect on
      the oscillation characteristics.

PMID- 14682990
TI  - Characterization of topological structure on complex networks.
AB  - Characterizing the topological structure of complex networks is a significant
      problem especially from the viewpoint of data mining on the World Wide Web. "Page
      rank" used in the commercial search engine Google is such a measure of authority
      to rank all the nodes matching a given query. We have investigated the page-rank
      distribution of the real Web and a growing network model, both of which have
      directed links and exhibit a power law distributions of in-degree (the number of
      incoming links to the node) and out-degree (the number of outgoing links from the
      node), respectively. We find a concentration of page rank on a small number of
      nodes and low page rank on high degree regimes in the real Web, which can be
      explained by topological properties of the network, e.g., network motifs, and
      connectivities of nearest neighbors.

PMID- 14682991
TI  - Wigner-Dyson statistics for a class of integrable models.
AB  - We construct an ensemble of second-quantized Hamiltonians with two bosonic
      degrees of freedom, whose members display with probability one Gaussian
      orthogonal ensemble (GOE) or Gaussian unitary ensemble (GUE) statistics.
      Nevertheless, these Hamiltonians have a second integral of motion, namely, the
      boson number, and thus are integrable. To construct this ensemble we use some
      "reverse engineering" starting from the fact that n bosons in a two-level system
      with random interactions have an integrable classical limit by the old Heisenberg
      association of boson operators to actions and angles. By choosing an n-body
      random interaction and degenerate levels we end up with GOE or GUE Hamiltonians.
      Ergodicity of these ensembles completes the example.

PMID- 14682992
TI  - Analytical results for coupled-map lattices with long-range interactions.
AB  - We obtain exact analytical results for lattices of maps with couplings that decay
      with distance as r(-alpha). We analyze the effect of the coupling range on the
      system dynamics through the Lyapunov spectrum. For lattices whose elements are
      piecewise linear maps, we get an algebraic expression for the Lyapunov spectrum.
      When the local dynamics is given by a nonlinear map, the Lyapunov spectrum for a
      completely synchronized state is analytically obtained. The critical line
      characterizing the synchronization transition is determined from the expression
      for the largest transversal Lyapunov exponent. In particular, it is shown that in
      the thermodynamical limit, such transition is only possible for sufficiently long
      range interactions, namely, for alpha<alpha(c)=d, where d is the lattice
      dimension.

PMID- 14682993
TI  - Role of inertia in two-dimensional deformation and breakdown of a droplet.
AB  - We investigate by lattice Boltzmann methods the effect of inertia on the
      deformation and breakdown of stability of a two-dimensional fluid droplet
      surrounded by fluid of equal viscosity (in a confined geometry) whose shear rate
      is increased very slowly. We give evidence that in two dimensions inertia is
      necessary for the loss of stability, so that at zero Reynolds number there is
      always a stable stationary droplet shape. We identify two different routes to
      breakdown, via two-lobed and three-lobed structures and give evidence for a sharp
      transition between these routes as parameters are varied.

PMID- 14682994
TI  - Vortices in dust clouds under microgravity: A simple explanation.
AB  - Clouds of dust particles in radio frequency discharges often show a periodic
      vortexlike motion, especially near the edges of the electrodes or near the tip of
      an electrostatic probe. These vortices often last as long as the discharge is
      powered. In a previous paper we have followed a small number of individual dust
      particles in a discharge under microgravity conditions, moving under the
      influence of forces computed by means of a self-consistent two-dimensional
      hydrodynamic model, and interacting via a screened Coulomb potential. The
      resulting motion showed the vortexlike rotation. In this paper we discuss this
      phenomenon in more detail, using a simplified model with harmonic forces, but
      extending the simulations to three dimensions. Stable vortices are observed,
      which show a more chaotic behavior than in the two-dimensional situation.
      Particles frequently jump up and down between two counterrotating vortices. The
      generation of the vortices can be ascribed to a nonzero rotation of the net
      global force vector field, which is the sum of the ion drag force, the electric
      force, and the thermophoretic force in case of the experiments. Comparison of
      experimental data with simulations using a model potential may open a way to
      unravel the forces inside a cloud of dust particles.

PMID- 14682995
TI  - Instabilities in the two-dimensional cubic nonlinear Schrodinger equation.
AB  - The two-dimensional cubic nonlinear Schrodinger equation (NLS) can be used as a
      model of phenomena in physical systems ranging from waves on deep water to pulses
      in optical fibers. In this paper, we establish that every one-dimensional
      traveling wave solution of NLS with linear phase is unstable with respect to some
      infinitesimal perturbation with two-dimensional structure. If the coefficients of
      the linear dispersion terms have the same sign (elliptic case), then the only
      unstable perturbations have transverse wavelength longer than a well-defined
      cutoff. If the coefficients of the linear dispersion terms have opposite signs
      (hyperbolic case), then there is no such cutoff and as the wavelength decreases,
      the maximum growth rate approaches a well-defined limit.

PMID- 14682996
TI  - Exact multilocal renormalization of the effective action: application to the
      random sine Gordon model statics and nonequilibrium dynamics.
AB  - We extend the exact multilocal renormalization group (RG) method to study the
      flow of the effective action functional. This important physical quantity
      satisfies an exact RG equation which is then expanded in multilocal components.
      Integrating the nonlocal parts yields a closed exact RG equation for the local
      part, to a given order in the local part. The method is illustrated on the O(N)
      model by straightforwardly recovering the eta exponent and scaling functions.
      Then it is applied to study the glass phase of the Cardy-Ostlund, random phase
      sine Gordon model near the glass transition temperature. The static correlations
      and equilibrium dynamical exponent z are recovered and several results are
      obtained, such as the equilibrium two-point scaling functions. The
      nonequilibrium, finite momentum, two-time t,t' response and correlations are
      computed. They are shown to exhibit scaling forms, characterized by exponents
      lambda(R) not equal lambda(C), as well as universal scaling functions that we
      compute. The fluctuation dissipation ratio is found to be nontrivial and of the
      form X[q(z)(t-t'),t/t']. Analogies and differences with pure critical models are
      discussed.

PMID- 14682997
TI  - Absolute transverse mobility and ratchet effect on periodic two-dimensional
      symmetric substrates.
AB  - We present a simple model of an overdamped particle moving on a two-dimensional
      symmetric periodic substrate with a dc drive in the longitudinal direction and
      additional ac drives in both the longitudinal and transverse directions. For
      certain regimes we find that a finite longitudinal dc force produces a net dc
      response only in the transverse direction, which we term absolute transverse
      mobility. Additionally, we find regimes exhibiting a ratchet effect in the
      absence of an applied dc drive.

PMID- 14682998
TI  - Persistence properties of a system of coagulating and annihilating random
      walkers.
AB  - We study a d-dimensional system of diffusing particles that on contact either
      annihilate with probability 1/(q-1) or coagulate with probability (q-2)/(q-1). In
      one dimension, the system models the zero-temperature Glauber dynamics of domain
      walls in the q-state Potts model. We calculate P(m,t), the probability that a
      randomly chosen lattice site contains a particle whose ancestors have undergone
      exactly (m-1) coagulations. Using perturbative renormalization group analysis for
      d<2, we show that, if the number of coagulations m is much less than the typical
      number M(t), then P(m,t) approximately m(zeta/d)t(-theta), with theta=dQ+Q(Q
      1/2)epsilon+O(epsilon(2)), zeta=(2Q-1)epsilon+(2Q-1)(Q
      1)(1/2+AQ)epsilon(2)+O(epsilon(3)), where Q=(q-1)/q, epsilon=2-d and A=
      0.006....M(t) is shown to scale as M(t) approximately t(d/2-delta), where
      delta=d(1-Q)+(Q-1)(Q-1/2)epsilon+O(epsilon(2)). In two dimensions, we show that
      P(m,t) approximately ln(t)(Q(3-2Q))ln(m)((2Q-1)(2))t(-2Q) for m<<t(2Q-1). We also
      derive an exact nonperturbative relation between the exponents: namely
      delta(Q)=theta(1-Q). The one-dimensional results corresponding to epsilon=1 are
      compared with results from Monte Carlo simulations.

PMID- 14682999
TI  - Stability of the iterative solutions of integral equations as one phase freezing
      criterion.
AB  - A recently proposed connection between the threshold for the stability of the
      iterative solution of integral equations for the pair correlation functions of a
      classical fluid and the structural instability of the corresponding real fluid is
      carefully analyzed. Direct calculation of the Lyapunov exponent of the standard
      iterative solution of hypernetted chain and Percus-Yevick integral equations for
      the one-dimensional (1D) hard rods fluid shows the same behavior observed in 3D
      systems. Since no phase transition is allowed in such 1D system, our analysis
      shows that the proposed one phase criterion, at least in this case, fails. We
      argue that the observed proximity between the numerical and the structural
      instability in 3D originates from the enhanced structure present in the fluid
      but, in view of the arbitrary dependence on the iteration scheme, it seems uneasy
      to relate the numerical stability analysis to a robust one-phase criterion for
      predicting a thermodynamic phase transition.

PMID- 14683000
TI  - Scaling of impact fragmentation near the critical point.
AB  - We investigated two-dimensional brittle fragmentation with a flat impact
      experimentally, focusing on the low-impact-energy region near the fragmentation
      critical point. We found that the universality class of fragmentation transition
      disagreed with that of percolation. However, the weighted mean mass of the
      fragments could be scaled using the pseudo-control-parameter multiplicity. The
      data for highly fragmented samples included a cumulative fragment mass
      distribution that clearly obeyed a power law. The exponent of this power law was
      0.5 and it was independent of sample size. The fragment mass distributions in
      this regime seemed to collapse into a unified scaling function using weighted
      mean fragment mass scaling. We also examined the behavior of higher-order moments
      of the fragment mass distributions, and obtained multiscaling exponents that
      agreed with those of the simple biased cascade model.

PMID- 14683001
TI  - Majority versus minority dynamics: phase transition in an interacting two-state
      spin system.
AB  - We introduce a simple model of opinion dynamics in which binary-state agents
      evolve due to the influence of agents in a local neighborhood. In a single update
      step, a fixed-size group is defined and all agents in the group adopt the state
      of the local majority with probability p or that of the local minority with
      probability 1-p. For group size G=3, there is a phase transition at p(c)=2/3 in
      all spatial dimensions. For p>p(c), the global majority quickly predominates,
      while for p<p(c), the system is driven to a mixed state in which the densities of
      agents in each state are equal. For p=p(c), the average magnetization (the
      difference in the density of agents in the two states) is conserved and the
      system obeys classical voter model dynamics. In one dimension and within a
      Kirkwood decoupling scheme, the final magnetization in a finite-length system has
      a nontrivial dependence on the initial magnetization for all p not equal p(c), in
      agreement with numerical results. At p(c), the exact two-spin correlation
      functions decay algebraically toward the value 1 and the system coarsens as in
      the classical voter model.

PMID- 14683002
TI  - Criticality versus q in the (2+1)-dimensional Zq clock model.
AB  - Using Monte Carlo simulations we have studied the d=3 Z(q) clock model in two
      different representations, the phase representation and the loop-gas/dumbbell-gas
      representation. We find that for q> or =5 the critical exponents alpha and nu for
      the specific heat and the correlation length, respectively, take on values
      corresponding to the case q--> infinity, the XY model. Hence in terms of critical
      properties the limiting behavior is reached already at q=5.

PMID- 14683003
TI  - Nonlinear stochastic equations with calculable steady states.
AB  - We consider generalizations of the Kardar-Parisi-Zhang equation that accommodate
      spatial anisotropies and the coupled evolution of several fields, and focus on
      their symmetries and nonperturbative properties. In particular, we derive
      generalized fluctuation-dissipation conditions on the form of the (nonlinear)
      equations for the realization of a Gaussian probability density of the fields in
      the steady state. For the amorphous growth of a single height field in one
      dimension we give a general class of equations with exactly calculable (Gaussian
      and more complicated) steady states. In two dimensions, we show that any
      anisotropic system evolves in long time and length scales either to the usual
      isotropic strong coupling regime or to a linearlike fixed point associated with a
      hidden symmetry. Similar results are derived for textural growth equations that
      couple the height field with additional order parameters which fluctuate on the
      growing surface. In this context, we propose phenomenological equations for the
      growth of a crystalline material, where the height field interacts with lattice
      distortions, and identify two special cases that obtain Gaussian steady states.
      In the first case compression modes influence growth and are advected by height
      fluctuations, while in the second case it is the density of dislocations that
      couples with the height.

PMID- 14683004
TI  - Spectra of complex networks.
AB  - We propose a general approach to the description of spectra of complex networks.
      For the spectra of networks with uncorrelated vertices (and a local treelike
      structure), exact equations are derived. These equations are generalized to the
      case of networks with correlations between neighboring vertices. The tail of the
      density of eigenvalues rho(lambda) at large /lambda/ is related to the behavior
      of the vertex degree distribution P(k) at large k. In particular, as P(k)
      approximately k(-gamma), rho(lambda) approximately /lambda/(1-2 gamma). We
      propose a simple approximation, which enables us to calculate spectra of various
      graphs analytically. We analyze spectra of various complex networks and discuss
      the role of vertices of low degree. We show that spectra of locally treelike
      random graphs may serve as a starting point in the analysis of spectral
      properties of real-world networks, e.g., of the Internet.

PMID- 14683005
TI  - Quantum iterated function systems.
AB  - An iterated function system (IFS) is defined by specifying a set of functions in
      a classical phase space, which act randomly on an initial point. In an analogous
      way, we define a quantum IFS (QIFS), where functions act randomly with prescribed
      probabilities in the Hilbert space. In a more general setting, a QIFS consists of
      completely positive maps acting in the space of density operators. This formalism
      is designed to describe certain problems of nonunitary quantum dynamics. We
      present exemplary classical IFSs, the invariant measure of which exhibits fractal
      structure, and study properties of the corresponding QIFSs and their invariant
      states.

PMID- 14683006
TI  - Phase transition in a swarm algorithm for self-organized construction.
AB  - This paper reports on a system where very simple, noncommunicating mobile agents
      in a cellular (lattice) environment use purely local rules to construct connected
      structures from initially randomly distributed building blocks. We study the
      effect of block density on the final structure, demonstrating a percolationlike
      phase transition: Low block densities lead to the formation of small,
      disconnected structures but a single connected structure emerges abruptly beyond
      a critical density. The empirical study of the structure at the transition point
      shows scaling behavior, providing strong evidence for criticality. We also
      demonstrate that a simple change of rules can completely change the phase
      transition effect. The results have implications for the self-organized
      construction of complex structures by swarms.

PMID- 14683007
TI  - Analytical results for a three-phase traffic model.
AB  - We study analytically a cellular automaton model, which is able to present three
      different traffic phases on a homogeneous highway. The characteristics displayed
      in the fundamental diagram can be well discerned by analyzing the evolution of
      density configurations. Analytical expressions for the traffic flow and shock
      speed are obtained. The synchronized flow in the intermediate-density region is
      the result of aggressive driving scheme and determined mainly by the stochastic
      noise.

PMID- 14683008
TI  - Self-consistent expansion results for the nonlocal Kardar-Parisi-Zhang equation.
AB  - In this paper various predictions for the scaling exponents of the nonlocal
      Kardar-Parisi-Zhang (NKPZ) equation are discussed. I use the self-consistent
      expansion (SCE), and obtain results that are quite different from the result
      obtained in the past, using dynamic renormalization-group analysis, a scaling
      approach, and a self-consistent mode-coupling approach. It is shown that the
      results obtained using SCE recover an exact result for a subfamily of the NKPZ
      models in one dimension, while all the other methods fail to do so. It is also
      shown that the SCE result is the only one that is compatible with simple
      observations on the dependence of the dynamic exponent z in the NKPZ model on the
      exponent rho characterizing the decay of the nonlinear interaction. The reasons
      for the failure of other methods to deal with NKPZ are also discussed.

PMID- 14683009
TI  - Self-organization from structural refrigeration.
AB  - The self-organization of a classical current is studied, in an exactly solvable
      model where both the quantum statistics over microhistories of particles, and the
      macroscopic phenomenology, can be computed in closed form. It is shown that for
      thermodynamically reversible systems, the Jaynes formulation of statistical
      mechanics naturally extends to include explicit macroscopic dynamics and
      heterogeneities in temperature, while preserving the structure of partition
      functions, effective potentials, and ground states of the equilibrium theory.
      Self-organization in such reversible systems is constrained by entropy transport
      through engine and refrigeration cycles, rather than by diffusion in gradients.
      Limitations in the ability to decompose such systems sensibly into components
      with additive entropies, and in the extrapolation of entropy functions from
      equilibrium forms, are discussed with examples.

PMID- 14683010
TI  - Exchange anisotropy and the dynamic phase transition in thin ferromagnetic
      Heisenberg films.
AB  - Monte Carlo simulations have been performed to investigate the dependence of the
      dynamic phase behavior on the bilinear exchange anisotropy of a classical
      Heisenberg spin system. The system under consideration is a planar thin
      ferromagnetic film with competing surface fields subject to a pulsed oscillatory
      external field. The results show that the films exhibit a single discontinuous
      dynamic phase transition (DPT) as a function of the anisotropy of the bilinear
      exchange interaction in the Hamiltonian. Furthermore, there is no evidence of
      stochastic resonance associated with the DPT. These results are in marked
      contrast to the continuous DPT observed in the same system as a function of
      temperature and applied field strength for a fixed bilinear exchange anisotropy.

PMID- 14683011
TI  - Software systems as complex networks: structure, function, and evolvability of
      software collaboration graphs.
AB  - Software systems emerge from mere keystrokes to form intricate functional
      networks connecting many collaborating modules, objects, classes, methods, and
      subroutines. Building on recent advances in the study of complex networks, I have
      examined software collaboration graphs contained within several open-source
      software systems, and have found them to reveal scale-free, small-world networks
      similar to those identified in other technological, sociological, and biological
      systems. I present several measures of these network topologies, and discuss
      their relationship to software engineering practices. I also present a simple
      model of software system evolution based on refactoring processes which captures
      some of the salient features of the observed systems. Some implications of object
      oriented design for questions about network robustness, evolvability, degeneracy,
      and organization are discussed in the wake of these findings.

PMID- 14683012
TI  - Martingale integrals over Poissonian processes and the Ito-type equations with
      white shot noise.
AB  - The construction of the Ito-type stochastic integrals and differential equations
      for compound Poisson processes is provided. The general martingale and
      nonanticipating properties of the ordinary (Gaussian) Ito theory are conserved.
      These properties appear particularly important if the stochastic description has
      to be proposed according to game theory or the linear relaxation (or the
      exponential growth) requirements. In contrast to the ordinary Ito theory the
      (uncorrelated) parametric fluctuation of a definite sign can be still modeled by
      asymmetric white shot noise, so the general scope of applications is not
      restricted by the positivity requirements. The possible use of the developed
      formalism in econophysics is addressed.

PMID- 14683013
TI  - Higher correlations, universal distributions, and finite size scaling in the
      field theory of depinning.
AB  - Recently we constructed a renormalizable field theory up to two loops for the
      quasistatic depinning of elastic manifolds in a disordered environment. Here we
      explore further properties of the theory. We show how higher correlation
      functions of the displacement field can be computed. Drastic simplifications
      occur, unveiling much simpler diagrammatic rules than anticipated. This is
      applied to the universal scaled width distribution. The expansion in d=4-epsilon
      predicts that the scaled distribution coincides to the lowest orders with the one
      for a Gaussian theory with propagator G(q)=1/q(d+2 zeta), zeta being the
      roughness exponent. The deviations from this Gaussian result are small and
      involve higher correlation functions, which are computed here for different
      boundary conditions. Other universal quantities are defined and evaluated: We
      perform a general analysis of the stability of the fixed point. We find that the
      correction-to-scaling exponent is omega=-epsilon and not -epsilon/3 as used in
      the analysis of some simulations. A more detailed study of the upper critical
      dimension is given, where the roughness of interfaces grows as a power of a
      logarithm instead of a pure power.

PMID- 14683014
TI  - Memory effects in microscopic traffic models and wide scattering in flow-density
      data.
AB  - By means of microscopic simulations we show that noninstantaneous adaptation of
      the driving behavior to the traffic situation together with the conventional
      method to measure flow-density data provides a possible explanation for the
      observed inverse-lambda shape and the wide scattering of flow-density data in
      "synchronized" congested traffic. We model a memory effect in the response of
      drivers to the traffic situation for a wide class of car-following models by
      introducing an additional dynamical variable (the "subjective level of service")
      describing the adaptation of drivers to the surrounding traffic situation during
      the past few minutes and couple this internal state to parameters of the
      underlying model that are related to the driving style. For illustration, we use
      the intelligent-driver model (IDM) as the underlying model, characterize the
      level of service solely by the velocity, and couple the internal variable to the
      IDM parameter "time gap" to model an increase of the time gap in congested
      traffic ("frustration effect"), which is supported by single-vehicle data. We
      simulate open systems with a bottleneck and obtain flow-density data by
      implementing "virtual detectors." The shape, relative size, and apparent
      "stochasticity" of the region of the scattered data points agree nearly
      quantitatively with empirical data. Wide scattering is even observed for
      identical vehicles, although the proposed model is a time-continuous,
      deterministic, single-lane car-following model with a unique fundamental diagram.

PMID- 14683015
TI  - Corrections to scaling in two-dimensional dynamic XY and fully frustrated XY
      models.
AB  - With large-scale Monte Carlo simulations, we investigate the two-dimensional
      dynamic XY and fully frustrated XY models. Dynamic relaxation starting from a
      disordered or an ordered state is carefully analyzed. It is confirmed that there
      is a logarithmic correction to scaling for a disordered start, but a power-law
      correction for an ordered start. Rather accurate values of the static exponent
      eta and the dynamic exponent z are estimated.

PMID- 14683016
TI  - Reaction-controlled diffusion: Monte Carlo simulations.
AB  - We study the coupled two-species nonequilibrium reaction-controlled diffusion
      model introduced by Trimper et al. [Phys. Rev. E 62, 6071 (2000)] by means of
      detailed Monte Carlo simulations in one and two dimensions. Particles of type A
      may independently hop to an adjacent lattice site, provided it is occupied by at
      least one B particle. The B particle species undergoes diffusion-limited
      reactions. In an active state with nonzero, essentially homogeneous B particle
      saturation density, the A species displays normal diffusion. In an inactive,
      absorbing phase with exponentially decaying B density, the A particles become
      localized. In situations with algebraic decay rho(B)(t) approximately t(
      alpha(B)), as occurring either at a nonequilibrium continuous phase transition
      separating active and absorbing states, or in a power-law inactive phase, the A
      particles propagate subdiffusively with mean-square displacement <x-->(t)(2)(A)>
      approximately t(1-alpha(A)). We find that within the accuracy of our simulation
      data, alpha(A) approximately alpha(B) as predicted by a simple mean-field
      approach. This remains true even in the presence of strong spatiotemporal
      fluctuations of the B density. However, in contrast with the mean-field results,
      our data yield a distinctly non-Gaussian A particle displacement distribution
      n(A)(x-->,t) that obeys dynamic scaling and looks remarkably similar for the
      different processes investigated here. Fluctuations of effective diffusion rates
      cause a marked enhancement of n(A)(x-->,t) at low displacements /x-->/,
      indicating a considerable fraction of practically localized A particles, as well
      as at large traversed distances.

PMID- 14683017
TI  - Dynamical model and nonextensive statistical mechanics of a market index on large
      time windows.
AB  - The shape and tails of partial distribution functions (PDF) for a financial
      signal, i.e., the S&P500 and the turbulent nature of the markets are linked
      through a model encompassing Tsallis nonextensive statistics and leading to
      evolution equations of the Langevin and Fokker-Planck type. A model originally
      proposed to describe the intermittent behavior of turbulent flows describes the
      behavior of normalized log returns for such a financial market index, for small
      and large time windows, and both for small and large log returns. These turbulent
      market volatility (of normalized log returns) distributions can be sufficiently
      well fitted with a chi(2) distribution. The transition between the small time
      scale model of nonextensive, intermittent process, and the large scale Gaussian
      extensive homogeneous fluctuation picture is found to be at ca. a 200 day time
      lag. The intermittency exponent kappa in the framework of the Kolmogorov log
      normal model is found to be related to the scaling exponent of the PDF moments,
      thereby giving weight to the model. The large value of kappa points to a large
      number of cascades in the turbulent process. The first Kramers-Moyal coefficient
      in the Fokker-Planck equation is almost equal to zero, indicating "no restoring
      force." A comparison is made between normalized log returns and mere price
      increments.

PMID- 14683018
TI  - Multicanonical Monte Carlo study and analysis of tails for the order-parameter
      distribution of the two-dimensional Ising model.
AB  - The tails of the critical order-parameter distribution of the two-dimensional
      Ising model are investigated through extensive multicanonical Monte Carlo
      simulations. Results for fixed boundary conditions are reported here, and
      compared with known results for periodic boundary conditions. Clear numerical
      evidence for "fat" stretched exponential tails exists below the critical
      temperature, indicating the possible presence of fat tails at the critical
      temperature. Our work suggests that the true order-parameter distribution at the
      critical temperature must be considered to be unknown at present.

PMID- 14683019
TI  - Level curvature distribution in a model of two uncoupled chaotic subsystems.
AB  - We study distributions of eigenvalue curvatures for a block-diagonal random
      matrix perturbed by a full random matrix. The most natural physical realization
      of this model is a quantum chaotic system with some inherent symmetry, such that
      its energy levels form two independent subsequences, subject to a generic
      perturbation which does not respect the symmetry. We describe analytically a
      crossover in the form of a curvature distribution with a tunable parameter,
      namely, the ratio of intersubsystem/intrasubsystem coupling strengths. We find
      that the peak value of the curvature distribution is much more sensitive to the
      changes in this parameter than the power-law tail behavior. This observation may
      help to clarify some qualitative features of the curvature distributions observed
      experimentally in acoustic resonances of quartz blocks.

PMID- 14683020
TI  - Adiabatic rocking ratchets: Optimum-performance regimes.
AB  - We analyze work and efficiency for an adiabatic rocking ratchet working under
      three operating regimes: maximum efficiency, maximum work, and a third one which
      represents a compromise between them. For all of these regimes the application of
      very concrete loads and external amplitudes is found necessary in order to obtain
      the maximum possible values of both efficiency and work. The reported results
      could be valuable to design efficient Brownian motors and compare their operation
      under different working regimes.

PMID- 14683021
TI  - Mean-field theory for clustering coefficients in Barabasi-Albert networks.
AB  - We applied a mean-field approach to study clustering coefficients in Barabasi
      Albert (BA) networks. We found that the local clustering in BA networks depends
      on the node degree. Analytic results have been compared to extensive numerical
      simulations finding a very good agreement for nodes with low degrees. Clustering
      coefficient of a whole network calculated from our approach perfectly fits
      numerical data.

PMID- 14683022
TI  - Diffusion in channeled structures: xenon in a crystalline sodalite.
AB  - The theory of Ronis and Vertenstein [J. Chem. Phys. 85, 1628 (1986)] is used to
      calculate the permeability of xenon in Theta-1, a crystalline sodalite containing
      one-dimensional channels. The required time-correlation functions are obtained
      from numerical simulations performed using a small number of target crystal
      atoms. The dynamics of the target atoms reproduce those of the full crystal by
      the means of a generalized Langevin equation of motion. An approximate expression
      for the potential of mean force inside the crystal is derived. The plane average
      space-dependent diffusion coefficient D(z) obeys the Smoluchowski prediction at
      infinite dilution. The permeability is reported and compared in detail with that
      obtained from transition state theory.

PMID- 14683023
TI  - Edge distribution method for solving elliptic boundary value problems with
      boundary singularities.
AB  - Elliptic boundary value problems are difficult to treat in the vicinity of
      singularities, i.e., edges and corners, of the boundary. The concentration of
      electrical charge on the edges and corners of a conductor is perhaps the simplest
      example of such problems. Here we provide a rapid method for accurate treatment
      of these problems. It utilizes a Green's-function-based implementation of last
      passage Monte Carlo diffusion methods. This is combined with a diffusion
      algorithm for the scaling of solutions to the Laplace equation near a corner
      singularity to yield the solution of a benchmark problem: the charge distribution
      near the edge and corner of a conducting cube.

PMID- 14683024
TI  - Minimal model for tag-based cooperation.
AB  - Recently, Riolo et al. [Nature (London) 414, 441 (2001)] showed by computer
      simulations that cooperation can arise without reciprocity when agents donate
      only to partners who are sufficiently similar to themselves. One striking outcome
      of their simulations was the observation that the number of tolerant agents that
      support a wide range of players was not constant in time, but showed
      characteristic fluctuations. The cause and robustness of these tides of tolerance
      remained to be explored. Here we clarify the situation by solving a minimal
      version of the model of Riolo et al. It allows us to identify a net surplus of
      random changes from intolerant to tolerant agents as a necessary mechanism that
      produces these oscillations of tolerance, which segregate different agents in
      time. This provides a new mechanism for maintaining different agents, i.e., for
      creating biodiversity. In our model the transition to the oscillating state is
      caused by a saddle node bifurcation. The frequency of the oscillations increases
      linearly with the transition rate from tolerant to intolerant agents.

PMID- 14683025
TI  - Topology of correlation-based minimal spanning trees in real and model markets.
AB  - We compare the topological properties of the minimal spanning tree obtained from
      a large group of stocks traded at the New York Stock Exchange during a 12-year
      trading period with the one obtained from surrogated data simulated by using
      simple market models. We find that the empirical tree has features of a complex
      network that cannot be reproduced, even as a first approximation, by a random
      market model and by the widespread one-factor model.

PMID- 14683026
TI  - Scaling of the linear response function from zero-field-cooled and thermoremanent
      magnetization in phase-ordering kinetics.
AB  - In this paper we investigate the relation between the scaling properties of the
      linear response function R(t,s), of the thermoremanent magnetization (TRM) and of
      the zero-field-cooled (ZFC) magnetization in the context of phase-ordering
      kinetics. We explain why the retrieval of the scaling properties of R(t,s) from
      those of TRM and ZFC magnetization is not trivial. Preasymptotic contributions
      generate a long crossover in TRM, while ZFC magnetization is affected by a
      dangerous irrelevant variable. Lack of understanding of both these points has
      generated some confusion in the literature. The full picture relating the
      exponents of all the quantities involved is explicitly illustrated in the
      framework of the large-N model. Following this scheme, an assessment of the
      present status of numerical simulations for the Ising model can be made. We reach
      the conclusion that on the basis of the data available up to now, statements on
      the scaling properties of R(t,s) can be made from ZFC magnetization but not from
      TRM. From ZFC data for the Ising model with d=2,3,4 we confirm the previously
      found linear dependence on dimensionality of the exponent a entering R(t,s)
      approximately s(-(1+a))f(t/s). We also find evidence that a recently derived form
      of the scaling function f(x), using local scale invariance arguments [M. Henkel,
      M. Pleimling, C. Godreche, and J. M. Luck, Phys. Rev. Lett. 87, 265701 (2001)],
      does not hold for the Ising model.

PMID- 14683027
TI  - Nonequilibrium transitions induced by the cross-correlation of white noises.
AB  - We study the role that the cross-correlation of noises plays in the statistical
      behavior of systems driven by two multiplicative Gaussian white noises. The
      temporal evolution of the system is described by a Langevin equation, for which
      we adopt a general interpretation that includes the Ito as well as the
      Stratonovich interpretation. We derive the stochastically equivalent Fokker
      Planck equation by means of the two-stage averaging of a state-dependent
      function. Analyzing the stationary solution of the Fokker-Planck equation for
      specific examples, we show explicitly that the cross-correlation of white noises
      can induce nonequilibrium transitions.

PMID- 14683028
TI  - Power-law persistence and trends in the atmosphere: a detailed study of long
      temperature records.
AB  - We use several variants of the detrended fluctuation analysis to study the
      appearance of long-term persistence in temperature records, obtained at 95
      stations all over the globe. Our results basically confirm earlier studies. We
      find that the persistence, characterized by the correlation C(s) of temperature
      variations separated by s days, decays for large s as a power law, C(s)
      approximately s(-gamma). For continental stations, including stations along the
      coastlines, we find that gamma is always close to 0.7. For stations on islands,
      we find that gamma ranges between 0.3 and 0.7, with a maximum at gamma=0.4. This
      is consistent with earlier studies of the persistence in sea surface temperature
      records where gamma is close to 0.4. In all cases, the exponent gamma does not
      depend on the distance of the stations to the continental coastlines. By varying
      the degree of detrending in the fluctuation analysis we obtain also information
      about trends in the temperature records.

PMID- 14683029
TI  - Chaos and its quantization in dynamical Jahn-Teller systems.
AB  - We investigate the E(g) x in circle e(g) Jahn-Teller system for the purpose of
      revealing the nature of quantum chaos in crystals. This system simulates the
      interaction between the nuclear vibrational modes and the electronic motion in
      non-Kramers doublets for multiplets of transition-metal ions. Inclusion of the
      anharmonic potential due to the trigonal symmetry in crystals makes the system
      nonintegrable and chaotic. Besides the quantal analysis of the transition from
      Poisson to Wigner level statistics with increasing the strength of anharmonicity,
      we study the effect of chaos on the electronic orbital angular momentum and
      explore the magnetic g-factor as a function of the system's energy. The regular
      oscillation of this factor changes to a rapidly decaying irregular oscillation by
      increasing the anharmonicity (chaoticity).

PMID- 14683030
TI  - Quantum diffusion in a biased kicked Harper system.
AB  - Quantum diffusion in a biased kicked Harper system, modeling field-induced
      transport in superlattices, is studied for fully chaotic dynamics of the
      underlying classical system. Under these conditions, the classical transport is
      diffusive whereas the quantum diffusion can be either enhanced or suppressed for
      commensurable or incommensurable ratio of the Bloch period to the driving period,
      respectively. The quantum transport properties are related to the statistical
      properties of the quasienergy spectra as described by random matrix theory.

PMID- 14683031
TI  - Localized behavior in the Lyapunov vectors for quasi-one-dimensional many-hard
      disk systems.
AB  - We introduce a definition of a "localization width" whose logarithm is given by
      the entropy of the distribution of particle component amplitudes in the Lyapunov
      vector. Different types of localization widths are observed, for example, a
      minimum localization width where the components of only two particles are
      dominant. We can distinguish a delocalization associated with a random
      distribution of particle contributions, a delocalization associated with a
      uniform distribution, and a delocalization associated with a wavelike structure
      in the Lyapunov vector. Using the localization width we show that in quasi-one
      dimensional systems of many hard disks there are two kinds of dependence of the
      localization width on the Lyapunov exponent index for the larger exponents: one
      is exponential and the other is linear. Differences due to these kinds of
      localizations also appear in the shapes of the localized peaks of the Lyapunov
      vectors, the Lyapunov spectra, and the angle between the spatial and momentum
      parts of the Lyapunov vectors. We show that the Krylov relation for the largest
      Lyapunov exponent lambda approximately -rho ln rho as a function of the density
      rho is satisfied (apart from a factor) in the same density region as the linear
      dependence of the localization widths is observed. It is also shown that there
      are asymmetries in the spatial and momentum parts of the Lyapunov vectors, as
      well as in their x and y components.

PMID- 14683032
TI  - Weyl formulas for annular ray-splitting billiards.
AB  - We consider the distribution of eigenvalues for the wave equation in annular
      (electromagnetic or acoustic) ray-splitting billiards. These systems are
      interesting in that the derivation of the associated smoothed spectral counting
      function can be considered as a canonical problem. This is achieved by extending
      a formalism developed by Berry and Howls for ordinary (without ray-splitting)
      billiards [Berry and Howls, Proc. R. Soc. London, Ser. A 447, 527 (1994)]. Our
      results are confirmed by numerical computations and permit us to infer a set of
      rules useful in order to obtain Weyl formulas for more general ray-splitting
      billiards.

PMID- 14683033
TI  - Wave function statistics in open chaotic billiards.
AB  - We study the statistical properties of wave functions in a chaotic billiard that
      is opened up to the outside world. Upon increasing the openings, the billiard
      wave functions cross over from real to complex. Each wave function is
      characterized by a phase rigidity, which is itself a fluctuating quantity. We
      calculate the probability distribution of the phase rigidity and discuss how
      phase rigidity fluctuations cause long-range correlations of intensity and
      current density. We also find that phase rigidities for wave functions with
      different incoming wave boundary conditions are statistically correlated.

PMID- 14683034
TI  - Unstable periodic orbits and discretization cycles.
AB  - Limit cycles that arise from discretizing the variable(s) of a nonlinear map are
      generally found to shadow individual unstable periodic orbits (UPOs) of the
      corresponding continuous map. In a few cases the discretization cycles can only
      be explained with other mechanisms, such as the near-occurrence of an UPO, or
      crossover between two or more UPOs.

PMID- 14683035
TI  - Classical scattering for a driven inverted Gaussian potential in terms of the
      chaotic invariant set.
AB  - We study the classical electron scattering from a driven inverted Gaussian
      potential, an open system, in terms of its chaotic invariant set. This chaotic
      invariant set is described by a ternary horseshoe construction on an appropriate
      Poincare surface of section. We find the development parameters that describe the
      hyperbolic component of the chaotic invariant set. In addition, we show that the
      hierarchical structure of the fractal set of singularities of the scattering
      functions is the same as the structure of the chaotic invariant set. Finally, we
      construct a symbolic encoding of the hierarchical structure of the set of
      singularities of the scattering functions and use concepts from the
      thermodynamical formalism to obtain one of the measures of chaos of the fractal
      set of singularities, the topological entropy.

PMID- 14683036
TI  - Ray chaos in optical cavities based upon standard laser mirrors.
AB  - We present a composite optical cavity made of standard laser mirrors; the cavity
      consists of a suitable combination of stable and unstable cavities. In spite of
      its very open nature the composite cavity shows ray chaos, which may be either
      soft or hard, depending on the cavity configuration. This opens a convenient
      route for experimental studies of the quantum aspects of a chaotic wave field.

PMID- 14683037
TI  - Estimation of interaction strength and direction from short and noisy time
      series.
AB  - A technique for determination of character and intensity of interaction between
      the elements of complex systems based on reconstruction of model equations for
      phase dynamics is extended to the case of short and noisy time series.
      Corrections, which eliminate systematic errors of the estimates, and expressions
      for confidence intervals are derived. Analytic results are presented for a
      particular case of linear uncoupled systems, and their validity for a much wider
      range of situations is demonstrated with numerical examples. The technique should
      be useful for the analysis of nonstationary processes in real time, including the
      situations of significant noise and restrictions on the observation time.

PMID- 14683038
TI  - Experimental observation of dramatic differences in the dynamic response of
      Newtonian and Maxwellian fluids.
AB  - An experimental study of the dynamic response of a Newtonian fluid and a
      Maxwellian fluid under an oscillating pressure gradient is presented. Laser
      Doppler anemometry is used in order to determine the velocity of the fluid inside
      a cylindrical tube. In the case of the Newtonian fluid, the dissipative nature is
      observed. In the dynamic response of the Maxwellian fluid an enhancement at the
      frequencies predicted by theory is observed.

PMID- 14683039
TI  - Dynamo effect in a driven helical flow.
AB  - The Roberts flow, a helical flow in the form of convectionlike rolls, is known to
      be capable of both kinematic and nonlinear dynamo action. We study the Roberts
      dynamo with particular attention being paid to the spatial structure of the
      generated magnetic field and its back-reaction on the flow. The dynamo
      bifurcation is decisively determined by the symmetry group of the problem, which
      is given by a subgroup of discrete transformations and a continuous translational
      invariance of the flow. In the bifurcation the continuous symmetry is broken
      while the discrete subgroup symmetry completely survives. Its actions help in
      understanding the spatial structures of the magnetic field and of the modified
      flow. In accordance with experimental observations, the magnetic field component
      perpendicular to the originally invariant direction is much stronger than the
      component in this direction. Furthermore, the magnetic field is largely
      concentrated in layers separating the convectionlike rolls of the flow and
      containing, in particular, its stagnation points, which are isolated for the
      modified flow while they are line filling for the original Roberts flow. The
      magnetic field is strongest near beta-type stagnation points, with a two
      dimensional unstable and a one-dimensional stable manifold, and is weak near
      alpha-type stagnation points, with a two-dimensional stable and a one-dimensional
      unstable manifold. This contrasts with the usual picture that dynamo action is
      promoted at the alpha points and impeded at the beta points. Both the creation of
      isolated stagnation points and the concentration of strong fields at the beta
      points may be understood as a result of the way in which the Roberts dynamo
      saturates. It is also found that, while the original Roberts flow is regular, the
      modified flow is chaotic in the layers between the convectionlike rolls where the
      magnetic field is concentrated. This chaoticity, which results from the back
      reaction of the magnetic field on the flow, appears to merely enhance magnetic
      diffusion rather than to strengthen the dynamo effect.

PMID- 14683040
TI  - Turbulence anisotropy and the SO3 description.
AB  - We study strongly turbulent windtunnel flows with controlled anisotropy. Using a
      recent formalism based on angular momentum and the irreducible representations of
      the SO(3) rotation group, we attempt to extract this anisotropy from the angular
      dependence of second-order structure functions. Our instrumentation allows a
      measurement of both the separation and the angle dependence of the structure
      function. In axisymmetric turbulence which has a weak anisotropy, this more
      extended information produces ambiguous results. In more strongly anisotropic
      shear turbulence, the SO(3) description enables one to find the anisotropy
      scaling exponent. The key quality of the SO(3) description is that structure
      functions are a mixture of algebraic functions of the scale with exponents
      ordered such that the contribution of anisotropies diminishes at small scales.
      However, we find that in third-order structure functions of homogeneous shear
      turbulence the anisotropic contribution is always large and of the same order of
      magnitude as the isotropic part. Our results concern the minimum instrumentation
      needed to determine the parameters of the SO(3) description, and raise several
      questions about its ability to describe the angle dependence of high-order
      structure functions.

PMID- 14683041
TI  - Intermittency in turbulence: computing the scaling exponents in shell models.
AB  - We discuss a stochastic closure for the equation of motion satisfied by
      multiscale correlation functions in the framework of shell models of turbulence.
      We present a plausible closure scheme to calculate the anomalous scaling
      exponents of structure functions by using the exact constraints imposed by the
      equation of motion. We present an explicit calculation for fifth-order scaling
      exponent by varying the free parameter entering in the nonlinear term of the
      model. The same method applied to the case of shell models for Kraichnan passive
      scalar provides a connection between the concept of zero-modes and time-dependent
      cascade processes.

PMID- 14683042
TI  - Stability of acoustic streaming flows in plane channels.
AB  - We study the stability of acoustic streaming flows of normal fluids induced by a
      small-amplitude surface acoustic wave propagating along the walls of a confined
      parallel-plane channel or slab in the incompressible flow regime. The secondary
      flows derived are of negligible effect to the stability characteristic after
      comparing with the primary flow. The governing equation which was derived by
      considering the weakly nonlinear coupling between the wavy wall and viscous fluid
      is obtained and then the eigenvalue problem is solved by a numerical code
      together with the associated dynamic and kinematic conditions. The value of the
      critical Reynolds number was found to be near 4873 which is smaller than the case
      5772 for conventional pressure-driven flows.

PMID- 14683043
TI  - Turbulence with pressure: anomalous scaling of a passive vector field.
AB  - The field theoretic renormalization group (RG) and the operator-product expansion
      are applied to the model of a transverse (divergence-free) vector quantity,
      passively advected by the "synthetic" turbulent flow with a finite (and not
      small) correlation time. The vector field is described by the stochastic
      advection-diffusion equation with the most general form of the inertial
      nonlinearity; it contains as special cases the kinematic dynamo model, linearized
      Navier-Stokes (NS) equation, the special model without the stretching term that
      possesses additional symmetries and has a close formal resemblance with the
      stochastic NS equation. The statistics of the advecting velocity field is
      Gaussian, with the energy spectrum E(k) proportional to k(1-epsilon) and the
      dispersion law omega proportional to k(-2+eta), k being the momentum (wave
      number). The inertial-range behavior of the model is described by seven regimes
      (or universality classes) that correspond to nontrivial fixed points of the RG
      equations and exhibit anomalous scaling. The corresponding anomalous exponents
      are associated with the critical dimensions of tensor composite operators built
      solely of the passive vector field, which allows one to construct a regular
      perturbation expansion in epsilon and eta; the actual calculation is performed to
      the first order (one-loop approximation), including the anisotropic sectors.
      Universality of the exponents, their (in)dependence on the forcing, effects of
      the large-scale anisotropy, compressibility, and pressure are discussed. In
      particular, for all the scaling regimes the exponents obey a hierarchy related to
      the degree of anisotropy: the more anisotropic is the contribution of a composite
      operator to a correlation function, the faster it decays in the inertial range.
      The relevance of these results for the real developed turbulence described by the
      stochastic NS equation is discussed.

PMID- 14683044
TI  - Parametric dependence of single-bubble sonoluminescence spectra.
AB  - We present experimental spectra of single sonoluminescing bubble in water at
      different dissolved argon concentrations and excitation levels. All the relevant
      experimental conditions are either measured directly or derived from measured
      quantities for each spectrum, thus the parametric dependence of the spectra can
      be analyzed. To characterize the data in a given wavelength interval we fitted
      the shape of the spectra with the Planck function. The effective temperatures
      obtained from these fits lie in the range 12,000-18,000 K, practically
      independent of the expansion ratio, while the intensity normalized by the volume
      of the bubble increases with the expansion ratio as a power law. The effective
      temperatures decrease with the pressure amplitude for each argon concentration,
      while the light intensity, measured with a photomultiplier tube, increases. These
      observations suggest that the increased energy input due to the higher pressure
      amplitudes results in an increased number of less energetic photons as compared
      to the case of a lower excitation level.

PMID- 14683045
TI  - Multizone shell model for turbulent wall bounded flows.
AB  - We suggested a multizone shell (MZS) model for wall-bounded flows accounting for
      the space inhomogeneity in a piecewise approximation, in which the cross
      sectional area of the flow, S, is subdivided into j zones. The area of the first
      zone, responsible for the core of the flow, S1 approximately S/2, and the areas
      of the next j zones, S(j), decrease toward the wall like S(j) proportional,
      variant 2(-j). In each j zone the statistics of turbulence is assumed to be space
      homogeneous and is described by the set of shell velocities u(nj)(t) for
      turbulent fluctuations of the scale proportional to 2(-n). The MZS model includes
      a set of complex variables V(j)(t), j=1,2, em leader, infinity, describing the
      amplitudes of the near-wall coherent structures of the scale s(j) approximately
      2(-j) and responsible for the mean velocity profile. The suggested MZS equations
      of motion for u(nj)(t) and V(j)(t) preserve the actual conservation laws (energy,
      mechanical, and angular momenta), respect the existing symmetries (including
      Galilean and scale invariance), and account for the type of nonlinearity in the
      Navier-Stokes equation, dimensional reasoning, etc. The MZS model qualitatively
      describes important characteristics of the wall-bounded turbulence, e.g.,
      evolution of the mean velocity profile with increasing Reynolds number Re from
      the laminar profile toward the universal logarithmic profile near the flat-plane
      boundary layer as Re--> infinity.

PMID- 14683046
TI  - Inertial particle segregation by turbulence.
AB  - We study collections of heavy and light small spherical particles initially well
      mixed with each other, subjected to linear (Stokes) drag force and gravity, and
      falling through a fluid turbulence. We introduce the segregation power spectrum,
      which we use to define the segregation length scale. Kinematic simulation
      predicts that the turbulence can segregate heavy and light falling particles and
      leads to a well-defined segregation length scale. The properties of this length
      scale and of the segregation power spectrum used to define it are discussed and,
      where possible, explained.

PMID- 14683047
TI  - Phase-field model of Hele-Shaw flows in the high-viscosity contrast regime.
AB  - A one-sided phase-field model is proposed to study the dynamics of unstable
      interfaces of Hele-Shaw flows in the high viscosity contrast regime. The
      corresponding macroscopic equations are obtained by means of an asymptotic
      expansion from the phase-field model. Numerical integrations of the phase-field
      model in a rectangular Hele-Shaw cell reproduce finger competition with the final
      evolution to a steady-state finger.

PMID- 14683048
TI  - Measurement of attractive interactions produced by the ion wakefield in dusty
      plasmas using a constrained collision geometry.
AB  - Plasma dust particle interactions, charges, and screening lengths are derived
      from measurements of time-dependent particle positions in a simplified geometry.
      The magnitude and structure of the ion wakefield potential below a negatively
      charged dust particle levitated in the plasma sheath region were measured as
      functions of the pressure and interparticle spacing. Attractive and repulsive
      components of the interaction force were extracted from a trajectory analysis of
      low-energy dust collisions between different mass particles in a well-defined
      electrostatic potential that constrained the dynamics of the collisions to be one
      dimensional. Typical peak attractions varied between 60 and 230 fN while the peak
      particle-particle repulsion was on the order of 60 fN. Random thermal motion of
      the particles contributed to observable rates for transitions between different
      equilibrium configurations of vertically separated particles. The influence of
      nearest- and non-nearest-neighbor interactions on calculated particle parameters
      is examined using several methods.

PMID- 14683049
TI  - Nonlinear compressional waves in a two-dimensional Yukawa lattice.
AB  - A modified Korteweg-de Vries (KdV) equation is obtained for studying the
      propagation of nonlinear compressional waves and pulses in a chain of particles
      including the effect of damping. Suitably altering the linear phase velocity
      makes this equation useful also for the problem of phonon propagation in a two
      dimensional (2D) lattice. Assuming a Yukawa potential, we use this method to
      model compressional wave propagation in a 2D plasma crystal, as in a recent
      experiment. By integrating the modified KdV equation the pulse is allowed to
      evolve, and good agreement with the experiment is found. It is shown that the
      speed of a compressional pulse increases with its amplitude, while the speed of a
      rarefactive pulse decreases. It is further discussed how the drag due to the
      background gas has a crucial role in weakening nonlinear effects and preventing
      the emergence of a soliton.

PMID- 14683051
TI  - Optical activity in an isotropic gas of electrons with a preferred helicity.
AB  - An isotropic gas of electrons with a preferred spin helicity is shown to be
      optically active. Simultaneous eigenfunctions of the Dirac Hamiltonian and the
      helicity operator are constructed and used to derive explicit expressions for
      vertex functions for helicity states. The (covariant) response tensor is
      calculated for an electron gas described in terms of a spin-dependent occupation
      number. The possibility of detecting optical activity in an electron gas is
      discussed briefly.

PMID- 14683050
TI  - Dispersion properties of the out-of-plane transverse wave in a two-dimensional
      Coulomb crystal.
AB  - The formation of a two-dimensional (2D) Coulomb crystal in a typical experimental
      environment was simulated with a computer code called BOX_TREE. The dispersion
      properties of a novel dust lattice wave (DLW) mode, the out-of-plane transverse
      wave, were obtained. The dispersion relation was determined to be an opticlike
      inverse dispersion when wave number k is lower than a critical value k(critical),
      and a positive dispersion when k>k(critical). The negative group velocity of the
      wave for k<k(critical) depends on the kappa value (with kappa=a/lambda(D), where
      a is the interparticle spacing and lambda(D) is the Debye length) and the
      positive group velocity for k>k(critical) depends on the propagation direction.
      The value of k(critical) depends on both kappa and propagation direction, but
      changes very little for all propagation directions and the range of kappa
      investigated. An analytical method has also been used to derive the dispersion
      relations assuming a hexagonal 2D lattice and Yukawa interparticle potential.
      These dispersion relations compare favorably with the simulation results. The
      dispersion relation for a 1D string was also obtained via BOX_TREE simulation and
      shown to agree with the analytical result given by Vladimirov [Physica A 315, 222
      (2002)]. Comparison shows that the out-of-plane transverse DLW in a 2D lattice
      when k<k(critical) has a negative group velocity much larger than that of the 1D
      string, given the same particle parameters and operating environment. Again
      k(critical) for 1D string and 2D lattice are in the same range.

PMID- 14683052
TI  - Solutions of complete jump relations at discontinuities in a two-and-half
      dimensional reconnection model.
AB  - We present an analytic solution of the complete set of jump relations at the
      rotational discontinuity and the slow-mode shock in a two-and-half-dimensional (2
      1/2D) symmetric reconnection model. The solution is used for analyzing the
      outflow jet characteristics in dependence on the speed and the incidence angle of
      the inflowing plasma, for a given shear of the inflow magnetic field. It is found
      that the magnetosonic Mach number of the outflow depends significantly on the
      incidence angle, the effect being more prominent at larger reconnection rates.
      The compression increases weakly with increasing reconnection rate. Dynamical
      changes in the flow/field geometry are found in the transition to the 2D regime:
      In the region between the rotational discontinuity and the slow-mode shock the
      direction of flow and the magnetic field become extremely sensitive to the degree
      of the magnetic field shear in the inflow. Implications for evolutionary systems
      such as solar flares are discussed.

PMID- 14683053
TI  - Negative ion motion in the mixtures of SF6 with CF4 and CH4-Ar.
AB  - This paper deals with the measurement of the mobility of negative ions in the
      mixtures of SF6 with CF4 and the CH4-Ar (50:50) binary mixture with SF6 contents
      up to 50%. The pulsed Townsend technique was used to observe the integrated ionic
      avalanches over a range of the density-reduced electric field E/N for which
      ionization is either negligible or absent, and attachment processes are
      significant, leading to the formation of mostly SF-6. The E/N range of
      measurement was from 1 to 70 Td (1 Td=10(-17) V cm(2)), over which the measured
      mobilities were found to be almost constant. The mobility of the negative ions
      was also measured for trace amounts of SF6 in CH4 and Ar and 1% CF4, thereby
      providing a good value of the mobility of SF-6 in these pure gases, in order to
      test the measured mobilities with Blanc's law. We have found good agreement,
      within quoted experimental uncertainties, between calculated and measured values.

PMID- 14683054
TI  - Ponderomotive acceleration of electrons by a tightly focused intense laser beam.
AB  - Ponderomotive force driven acceleration of an electron at the focus of a high
      intensity short-pulse laser is considered. Accounting for the asymmetry of
      acceleration and deceleration due to the evolution of the Gaussian laser beam
      waist, the energized electron is extracted from the laser pulse by the
      longitudinal ponderomotive force. It is shown that an electron's energy gain in
      the range of MeV can be realized for laser intensities above 10(19) W
      microm(2)/cm(2). Final energy gain as a function of the scattering angle and the
      electron's initial position has also been discussed.

PMID- 14683055
TI  - Ion mobilities in Xe/Ne and other rare-gas mixtures.
AB  - The ion mobility or drift velocity data important for modeling glow discharges in
      rare gas mixtures are not generally available, nor are the ion-neutral scattering
      cross sections needed to calculate these data. In this paper we propose a set of
      cross sections for Xe+ and Ne+ collisions with Xe and Ne atoms. Ion mobilities at
      300 K calculated using this cross section set in a Monte Carlo simulation are
      reported for reduced field strengths, E/N, up to 1500 x 10(-21) V m(2), in pure
      gases and in Xe/Ne mixtures containing 5% and 20% Xe/Ne, which are mixtures of
      interest for plasma display panels (PDPs). The calculated Xe+ mobilities depend
      strongly on the mixture composition, but the Ne+ mobility varies only slightly
      with increasing Xe in the mixture over the range studied here. The mobilities in
      pure gases compare well with available experimental values, and mobilities in gas
      mixtures at low E/N compare well with our recent measurements which will be
      published separately. Results from these calculations of ion mobilities are used
      to evaluate the predictions of Blanc's law and of the mixture rule proposed by
      Mason and Hahn [Phys. Rev. A 5, 438 (1972)] for determining the ion mobilities in
      mixtures from a knowledge of the mobilities in each of the pure gases. The
      mixture rule of Mason and Hahn is accurate to better than 10% at high field
      strengths over a wide range of conditions of interest for modeling PDPs. We
      conclude that a good estimate of ion mobilities at high E/N in Xe/Ne and other
      binary rare gas mixtures can be obtained using this mixture rule combined with
      known values of mobilities in parent gases and with the Langevin form for
      mobility of rare gas ions ion in other gases. This conclusion is supported by
      results in Ar/Ne mixtures which are also presented here.

PMID- 14683056
TI  - Drift-wave turbulence and zonal flow generation.
AB  - Drift-wave turbulence in a plasma is analyzed on the basis of the wave Liouville
      equation, describing the evolution of the distribution function of wave packets
      (quasiparticles) characterized by position x and wave vector k. A closed kinetic
      equation is derived for the ensemble-averaged part of this function by the
      methods of nonequilibrium statistical mechanics. It has the form of a non
      Markovian advection-diffusion equation describing coupled diffusion processes in
      x and k spaces. General forms of the diffusion coefficients are obtained in terms
      of Lagrangian velocity correlations. The latter are calculated in the
      decorrelation trajectory approximation, a method recently developed for an
      accurate measure of the important trapping phenomena of particles in the rugged
      electrostatic potential. The analysis of individual decorrelation trajectories
      provides an illustration of the fragmentation of drift-wave structures in the
      radial direction and the generation of long-wavelength structures in the poloidal
      direction that are identified as zonal flows.

PMID- 14683057
TI  - Vector and tensor polarization lifetimes for a stored deuteron beam.
AB  - The time dependence of the vector and tensor polarization of a 270 MeV stored
      deuteron beam was measured near a depolarizing resonance, which was induced by an
      oscillating, longitudinal magnetic field. The distance to the resonance was
      varied by changing the oscillation frequency. The measured ratio of the
      polarization lifetimes is tau(vector)/tau(tensor)=1.9+/-0.2. Assuming that the
      effect of the resonance is to induce transitions between magnetic substates m(I),
      we find that the transition rate between neighboring states (+1 and 0 or -1 and
      0) is four times higher than between the states with m(I)=+1 and -1.

PMID- 14683058
TI  - Explicit symplectic integrator for s-dependent static magnetic field.
AB  - This paper reports our recent work on explicit symplectic integration techniques
      for the charged particle motion in an s-dependent static magnetic field. Using
      the extended phase space, symplectic integrators can be developed for
      Hamiltonians with or without the paraxial approximation using either the space or
      time as an independent variable. This work extends the successful element-by
      element tracking method for studying single-particle nonlinear dynamics to a set
      of s-dependent magnetic elements. Important applications of this work include the
      studies of the charged particle dynamics in a storage ring with various insertion
      devices, superconducting magnets, large aperture magnets with significant fringe
      fields, and solenoid magnets in the interaction region. Consequently, this work
      is expected to make an impact on design and optimal operation of existing and
      future light source rings and high energy physics accelerators.

PMID- 14683059
TI  - Construction of one-dimensional photonic crystals based on the incident angle
      domain.
AB  - An effective method used to extend the band gap of hybrid one-dimensional
      photonic crystals is proposed. This method does not require one-dimensional
      photonic crystals used in the construction of hybrid photonic crystals to have
      omnidirectional photonic band gaps. This property gives the designers more
      freedom to select materials used in the design. Another advantage of this method
      is the ability to obtain very large omnidirectional photonic band gaps of hybrid
      structures without using too many one-dimensional photonic crystals. Some
      structures are constructed by this method to prove it. By using TiO2 and SiO2,
      the structure composed of four one-dimensional photonic crystals based on this
      method has been calculated and fabricated. The theoretical relative bandwidth of
      an omnidirectional photonic band gap is 41.33%, and the experimental result is up
      to 37%, which is very large in the visible region. By comparison, the theoretical
      relative bandwidth of the conventional method based on the frequency domain is
      only 14.26%.

PMID- 14683060
TI  - Coupling of the TE and TM modes of electromagnetic waves in two-dimensional
      photonic crystals with surface defects of liquid crystals.
AB  - We theoretically demonstrate the coupling of the TE and TM modes of
      electromagnetic waves in two-dimensional photonic crystals with surface defects
      of liquid crystals. Due to anisotropies of liquid crystals, the TE and TM modes
      cannot be classified generally in the surface defects, which causes the coupling
      of the TE and TM modes. The coupling of the TE and TM modes occurs strongly at
      frequencies at which group velocities of electromagnetic waves become zero,
      especially at surface defect modes. Possibility of the sharp tunability and the
      switching of the transmittance in this system has been demonstrated theoretically
      by the control of directors of liquid crystals by applied electric field due to
      their anisotropy.

PMID- 14683061
TI  - Four-wave mixing instabilities in photonic-crystal and tapered fibers.
AB  - Four-wave mixing instabilities are theoretically studied for continuous wave
      propagation in ultrasmall core photonic-crystal and tapered fibers. The
      waveguide, or geometrical, contribution to the overall dispersion of these
      structures is much stronger than in conventional fibers. This leads to the
      appearance of unstable frequency bands that are qualitatively and quantitatively
      different from those seen in conventional fibers. The four-wave mixing theory
      developed here is based on the full wave equation, which allows rigorous study of
      the unstable bands even when the detunings are of the order of the pump frequency
      itself. Solutions obtained using the generalized nonlinear Schrodinger equation,
      which is an approximate version of the full wave equation, reveal that it suffers
      from several deficiencies when used to describe four-wave mixing processes.

PMID- 14683062
TI  - Soliton collisions in the discrete nonlinear Schrodinger equation.
AB  - We report analytical and numerical results for on-site and intersite collisions
      between solitons in the discrete nonlinear Schrodinger model. A semianalytical
      variational approximation correctly predicts gross features of the collision,
      viz., merger or bounce. We systematically examine the dependence of the collision
      outcome on initial velocity and amplitude of the solitons, as well as on the
      phase shift between them, and location of the collision point relative to the
      lattice; in some cases, the dependences are very intricate. In particular, merger
      of the solitons into a single one, and bounce after multiple collisions are
      found. Situations with a complicated system of alternating transmission and
      merger windows are identified too. The merger is often followed by symmetry
      breaking (SB), when the single soliton moves to the left or to the right, which
      implies momentum nonconservation. Two different types of the SB are identified,
      deterministic and spontaneous. The former one is accounted for by the location of
      the collision point relative to the lattice, and/or the phase shift between the
      solitons; the momentum generated during the collision due to the phase shift is
      calculated in an analytical approximation, its dependence on the solitons'
      velocities comparing well with numerical results. The spontaneous SB is explained
      by the modulational instability of a quasiflat plateau temporarily formed in the
      course of the collision.

PMID- 14683063
TI  - Exact soliton solutions for the core of dispersion-managed solitons.
AB  - We consider the averaged dispersion-managed (DM) fiber system equation, which
      governs the dynamics of the core of the DM solitons. For a special case of such a
      system equation, we derive the exact soliton solutions using the Darboux
      transformation. Further, we discuss the interaction scenario between two
      neighboring solitons. Finally, we derive a dark soliton solution for such a
      system by assuming an ansatz, and the interaction between neighboring dark
      solitons is discussed.

PMID- 14683064
TI  - Optical bistability involving photonic crystal microcavities and Fano line
      shapes.
AB  - The reflectivity of a single-channel waveguide mode upon resonantly coupling to a
      Kerr-active nonlinear resonant cavity is calculated analytically, including the
      effects of two-photon absorption. The resonant reflectivity takes the form of a
      Fano resonance because the solution includes linear reflections from
      perturbations downstream of the localized cavity. Instead of using a Hamiltonian
      formulation of the scattering problem, an intuitive set of basis states is used
      to expand the Green's function of the electric field wave equation. All resulting
      overlap functions describing the linear coupling between guided and localized
      states, and the nonlinear renormalization of the material's refractive index, are
      in terms of well-defined physical quantities. Although derived in the context of
      photonic crystal-based waveguides and cavities, the treatment is valid for any
      low-loss waveguide-resonator geometry that satisfies specific weak coupling
      criteria. For a cavity consisting of Al0.18Ga0.82As, hosting a localized mode at
      1.55 microm with a Q of 4000 and a mode volume of 0.055 microm(3), we predict the
      onset of bistable reflection at incident powers of approximately 40 mW. The
      downstream reflections lead to hysteresis loops in the reflectivity that are
      topologically distinct from conventional Lorentzian-derived loops characteristic
      of isolated Fabry-Perot cavities. We provide a stability argument that reveals
      the unstable branches of these unique hysteresis loops, and we illustrate some of
      the rich bistable behaviors that can be engineered with such downstream sources.

PMID- 14683065
TI  - Blueprint for wafer-scale three-dimensional photonic band-gap synthesis by
      photoelectrochemical etching.
AB  - We present an architecture for three-dimensional photonic band-gap (PBG) material
      synthesis by oblique angle photoelectrochemical pore etching. This technique
      provides high aspect ratio pores, in which the pore diameter can be modulated by
      changing light intensity during the etch process. The naturally occurring
      "Kielovite" structure is a stretched version of the face-centered-cubic lattice
      of crisscrossing pores and exhibits a PBG to center frequency ratio of 8% in a
      background dielectric constant of 11.9 (silicon). We demonstrate that by
      modulating the pore radius in between pore intersections, the PBG can be doubled
      in size to nearly 16%. The enlarged PBG is robust against a number of structural
      perturbations.

PMID- 14683066
TI  - Diffusive and localization behavior of electromagnetic waves in a two-dimensional
      random medium.
AB  - In this paper, we discuss the transport phenomena of electromagnetic waves in a
      two-dimensional random system which is composed of arrays of electrical dipoles,
      following the model presented earlier by Erdogan et al. [J. Opt. Soc. Am. B 10,
      391 (1993)]. A set of self-consistent equations is presented, accounting for the
      multiple scattering in the system, and is then solved numerically. A strong
      localization regime is discovered in the frequency domain. The transport
      properties within, near the edge of, and nearly outside the localization regime
      are investigated for different parameters such as filling factor and system size.
      The results show that within the localization regime, waves are trapped near the
      transmitting source. Meanwhile, the diffusive waves follow an intuitive but
      expected picture. That is, they increase with traveling path as more and more
      random scattering incurs, followed by a saturation, then start to decay
      exponentially when the travelling path is large enough, signifying the
      localization effect. For the cases where the frequencies are near the boundary of
      or outside the localization regime, the results of diffusive waves are compared
      with the diffusion approximation, showing less encouraging agreement as in other
      systems [Asatryan et al., Phys. Rev. E 67, 036605 (2003)].

PMID- 14683067
TI  - Metastability of dark snoidal-type waves in quadratic nonlinear media.
AB  - We report the existence and basic properties of dark snoidal-type waves self
      sustained in quadratic nonlinear media. Using a stability analysis technique, we
      reveal that they are almost completely stable, or metastable, in suitable ranges
      of input energy flows and material parameters. This opens the way to the
      experimental observation of dark-type multicolor periodic wave patterns supported
      by quadratic nonlinearities.

PMID- 14683068
TI  - Averaged dynamics of optical pulses described by a nonlinear Schrodinger equation
      with periodic coefficients.
AB  - A nonlinear Schrodinger equation with periodic coefficients, as it appears, e.g.,
      in nonlinear optics, is considered. The high-frequency, variable part of the
      dispersion may be even much larger than the mean value. The ratio of the length
      of the dispersion map to the period of a solution is assumed as one small
      parameter. The second one corresponds to the integral over the variable part of
      the dispersion. For the averaged dynamics, we propose a procedure based on the
      Bogolyubov method. As a result, we obtain the asymptotic equation in the
      dominating order, as well as with the next corrections. The equation is valid for
      all combinations of the small parameters. The explicit forms of the coefficients
      are presented for a two-step dispersion map with an exponential loss function.
      The forms of the bright and black soliton solutions are discussed. The results
      are compared to those from other averaging methods, namely, the multiple-scale
      method and the method based on Lie transformations.

PMID- 14683069
TI  - Electric potential for a resistive toroidal conductor carrying a steady azimuthal
      current.
AB  - In this work we treat a resistive toroidal conductor carrying a steady azimuthal
      current. We calculate the electric potential everywhere in space. We also present
      the electric field inside and outside the toroid and the surface charge
      distribution along the conductor. We compare our theoretical result with
      Jefimenko's experiment.

PMID- 14683070
TI  - Robust soliton clusters in media with competing cubic and quintic nonlinearities.
AB  - Systematic results are reported for dynamics of circular patterns ("necklaces"),
      composed of fundamental solitons and carrying orbital angular momentum, in the
      two-dimensional model, which describes the propagation of light beams in bulk
      media combining self-focusing cubic and self-defocusing quintic nonlinearities.
      Semianalytical predictions for the existence of quasistable necklace structures
      are obtained on the basis of an effective interaction potential. Then, direct
      simulations are run. In the case when the initial pattern is far from an
      equilibrium size predicted by the potential, it cannot maintain its shape.
      However, a necklace with the initial shape close to the predicted equilibrium
      survives very long evolution, featuring persistent oscillations. The quasistable
      evolution is not essentially disturbed by a large noise component added to the
      initial configuration. Basic conclusions concerning the necklace dynamics in this
      model are qualitatively the same as in a recently studied one which combines
      quadratic and self-defocusing cubic nonlinearities. Thus, we infer that a
      combination of competing self-focusing and self-defocusing nonlinearities
      enhances the robustness not only of vortex solitons but also of vorticity
      carrying necklace patterns.

PMID- 14683071
TI  - Slowing light in chi2 photonic crystals.
AB  - A study of parametric nonlinear frequency down-conversion in photonic crystals
      reveals that under suitable conditions the probe field can be slowed down to
      approximately 11 m/s. The effect arises as a result of the simultaneous
      availability of global phase-matching conditions, field localization, and gain
      experienced by the probe beam. Together, these effects conspire to yield
      tunneling velocities previously reported only for coherently resonant
      interactions, i.e., electromagnetic induced transparency, in Bose-Einstein
      condensates, hot atomic gases, and doped crystals.

PMID- 14683072
TI  - Bridging the microscopic and macroscopic theories for light reflected from
      disordered plane-parallel dielectric slabs.
AB  - For a system of randomly arranged plane-parallel dielectric layers with randomly
      varying index of refraction and width, we compare the reflection coefficient
      derived from the Maxwell equations with that of the Boltzmann theory. For a
      strictly monochromatic field this coefficient is an oscillatory function of the
      laser frequency. We show how suitable frequency or ensemble averaging permits a
      comparison of the two theories. The calculation of the usual Boltzmann scattering
      coefficient from microscopic parameters can be improved to permit a better
      agreement with the exact Maxwell data.

PMID- 14683073
TI  - Nonequilibrium molecular dynamics simulation of gas-mixtures transport in carbon
      nanopore membranes.
AB  - The numerical simulation of nonequilibrium cotransport of H2 and alkane gas
      mixtures with very different molecular sizes through a porous carbon membrane
      structure was implemented. Simulated permeabilities and selectivities in binary
      diffusive systems (and in one ternary system), at pressure about tens of
      atmospheres and at operating condition of room temperature or higher, can be
      predicted from single-gas permeabilities. This suggests that the effect is
      geometrical and an approximate model of the transport is proposed. It can be used
      for an estimation of the separation factor of a membrane. Simulations are
      compared with experimental results of two- and three-component codiffusion and
      counterdiffusion in a carbon membrane. It is shown that diffusion in a porous
      molecular network and in a carbon nanotube are completely different. The
      uniqueness of this work lies in the comparison of simulated, approximate, and
      experimental results, which enables us to identify the important parameters.

PMID- 14683074
TI  - Dissipative particle dynamics: a useful thermostat for equilibrium and
      nonequilibrium molecular dynamics simulations.
AB  - We discuss dissipative particle dynamics as a thermostat to molecular dynamics,
      and highlight some of its virtues: (i) universal applicability irrespective of
      the interatomic potential; (ii) correct and unscreened reproduction of
      hydrodynamic correlations; (iii) stabilization of the numerical integration of
      the equations of motion; and (iv) the avoidance of a profile bias in boundary
      driven nonequilibrium simulations of shear flow. Numerical results on a repulsive
      Lennard-Jones fluid illustrate our arguments.

PMID- 14683075
TI  - Designing refoldable model molecules.
AB  - We report a numerical study of the design of lattice heteropolymers that can
      refold when the properties of only a few monomers are changed. If we assume that
      the effect of an external agent on a heteropolymer is to alter the interactions
      between its constituent monomers, our simulations provide a description of a
      simple allosteric transition. We characterize the free energy surfaces of the
      initial and the modified chain molecule. We find that there is a region of
      conformation space where molecules can be made to refold with minimal free energy
      cost. This region is accessible by thermal fluctuations. The efficiency of a
      motor based on such an allosteric transition would be enhanced by "borrowing"
      heat from the environment in the initial stages of the refolding, and "paying
      back" later. In fact, the power cycle of many real molecular motors does involve
      such a borrowing activation step.

PMID- 14683076
TI  - Nonideal gas flow and heat transfer in micro- and nanochannels using the direct
      simulation Monte Carlo method.
AB  - Subsonic nonideal gas flow and heat transfer in micro- and nanochannels for
      different Knudsen numbers are investigated numerically using the direct
      simulation Monte Carlo method modified with a consistent Boltzmann algorithm. The
      van der Waals equation is used as the equation of state. The collision rate is
      also modified based on the Enskog theory for dense gas. It is shown that the
      nonideal gas effect becomes significant when the gas becomes so dense that the
      ideal gas assumption breaks down. The results also show that the nonideal gas
      effect is dependent not only on the gas density, but also on the channel size. A
      higher gas density and a smaller channel size lead to a more significant nonideal
      gas effect. The nonideal gas effect also causes lower skin friction coefficients
      and different heat transfer flux distributions at the wall surface. The
      simulations presented in this work are helpful for a better understanding of
      micro- and nanoscale gas flows.

PMID- 14683077
TI  - Update statistics in conservative parallel-discrete-event simulations of
      asynchronous systems.
AB  - We model the performance of an ideal closed chain of L processing elements that
      work in parallel in an asynchronous manner. Their state updates follow a generic
      conservative algorithm. The conservative update rule determines the growth of a
      virtual time surface. The physics of this growth is reflected in the utilization
      (the fraction of working processors) and in the interface width. We show that it
      is possible to make an explicit connection between the utilization and the
      microscopic structure of the virtual time interface. We exploit this connection
      to derive the theoretical probability distribution of updates in the system
      within an approximate model. It follows that the theoretical lower bound for the
      computational speedup is s=(L+1)/4 for L> or =4. Our approach uses simple
      statistics to count distinct surface-configuration classes consistent with the
      model growth rule. It enables one to compute analytically microscopic properties
      of an interface, which are unavailable by continuum methods.

PMID- 14683078
TI  - Near-optimal configurations in mean-field disordered systems.
AB  - We present a general technique to compute how the energy of a configuration
      varies as a function of its overlap with the ground state in the case of
      optimization problems. Our approach is based on a generalization of the cavity
      method to a system interacting with its ground state. With this technique we
      study the random matching problem as well as the mean-field diluted spin glass.
      As a by-product of this approach we calculate the de Almeida-Thouless transition
      line of the spin glass on a fixed connectivity random graph.

PMID- 14683079
TI  - Backflow correlations for the electron gas and metallic hydrogen.
AB  - We justify and evaluate backflow three-body wave functions for a two-component
      system of electrons and protons. Based on the generalized Feynman-Kacs formula,
      many-body perturbation theory, and band structure calculations, we analyze the
      use and the analytical form of the backflow function from different points of
      view. The resulting wave functions are used in variational and diffusion Monte
      Carlo calculations of the electron gas and of solid and liquid metallic hydrogen.
      For the electron gas, the purely analytic backflow and three-body form gives
      lower energies than those of previous calculations. For bcc hydrogen, analytical
      and optimized backflow-three-body wave functions lead to energies nearly as low
      as those from using local density approximation orbitals in the trial wave
      function. However, compared to wave functions constructed from density functional
      solutions, backflow wave functions have the advantage of only few parameters to
      estimate, the ability to include easily and accurately electron-electron
      correlations, and that they can be directly generalized from the crystal to a
      disordered liquid of protons.

PMID- 14683080
TI  - Quantum Monte Carlo algorithm for softcore boson systems.
AB  - An efficient quantum Monte Carlo algorithm for the simulation of bosonic systems
      on a lattice in a grand canonical ensemble is proposed. It is based on the
      mapping of bosonic models to the spin models in the limit of the infinite total
      spin quantum number. It is demonstrated how this limit may be taken explicitly in
      the algorithm, eliminating the systematic errors. The efficiency of the algorithm
      is examined for the noninteracting lattice boson model and compared with the
      stochastic series expansion method with the heat-bath-type scattering probability
      of the random walker.

PMID- 14683081
TI  - Numerical viscosity and resolution of high-order weighted essentially
      nonoscillatory schemes for compressible flows with high Reynolds numbers.
AB  - A quantitative study is carried out in this paper to investigate the size of
      numerical viscosities and the resolution power of high-order weighted essentially
      nonoscillatory (WENO) schemes for solving one- and two-dimensional Navier-Stokes
      equations for compressible gas dynamics with high Reynolds numbers. A one
      dimensional shock tube problem, a one-dimensional example with parameters
      motivated by supernova and laser experiments, and a two-dimensional Rayleigh
      Taylor instability problem are used as numerical test problems. For the two
      dimensional Rayleigh-Taylor instability problem, or similar problems with small
      scale structures, the details of the small structures are determined by the
      physical viscosity (therefore, the Reynolds number) in the Navier-Stokes
      equations. Thus, to obtain faithful resolution to these small-scale structures,
      the numerical viscosity inherent in the scheme must be small enough so that the
      physical viscosity dominates. A careful mesh refinement study is performed to
      capture the threshold mesh for full resolution, for specific Reynolds numbers,
      when WENO schemes of different orders of accuracy are used. It is demonstrated
      that high-order WENO schemes are more CPU time efficient to reach the same
      resolution, both for the one-dimensional and two-dimensional test problems.

PMID- 14683082
TI  - Quantitative description and modeling of real networks.
AB  - We present data analysis and modeling of two particular cases of study in the
      field of growing networks. We analyze World Wide Web data set and authorship
      collaboration networks in order to check the presence of correlation in the data.
      The results are reproduced with good agreement through a suitable modification of
      the standard Albert-Barabasi model of network growth. In particular, intrinsic
      relevance of sites plays a role in determining the future degree of the vertex.

PMID- 14683083
TI  - Topology and computational performance of attractor neural networks.
AB  - To explore the relation between network structure and function, we studied the
      computational performance of Hopfield-type attractor neural nets with regular
      lattice, random, small-world, and scale-free topologies. The random configuration
      is the most efficient for storage and retrieval of patterns by the network as a
      whole. However, in the scale-free case retrieval errors are not distributed
      uniformly among the nodes. The portion of a pattern encoded by the subset of
      highly connected nodes is more robust and efficiently recognized than the rest of
      the pattern. The scale-free network thus achieves a very strong partial
      recognition. The implications of these findings for brain function and social
      dynamics are suggestive.

PMID- 14683084
TI  - Scale-free networks from a Hamiltonian dynamics.
AB  - Contrary to many recent models of growing networks, we present a model with fixed
      number of nodes and links, where a dynamics favoring the formation of links
      between nodes with degree of connectivity as different as possible is introduced.
      By applying a local rewiring move, the network reaches equilibrium states
      assuming broad degree distributions, which have a power-law form in an
      intermediate range of the parameters used. Interestingly, in the same range we
      find nontrivial hierarchical clustering.

PMID- 14683085
TI  - Growth behavior of helical cellular automata.
AB  - A helical cellular automata (HCA) model constructed on a two-dimensional grid of
      cells with a helical structure is presented and the pattern formation of this
      model studied by numerous computer simulations. It is found that the evolutions
      of the HCA are sensitive to the circumference of the helix p. With various p, the
      initial growth of the model generates various patterns ranging from Sierpinski
      triangle gasket, complex textured pattern, to lateral quasiperiodic structure. A
      sudden transition from regular fractal to compact pattern occurs near the point
      where p is equal to a positive integer power of 2. With increasing height of the
      patterns (increasing growth time), the model also exhibits different growth
      behaviors in the vertical direction for various p, including the formation of
      regular periodic patterns and the evolution from initial regular patterns to
      eventual random structures. Fractal dimension analysis is used to characterize
      these different evolution processes quantitatively.

PMID- 14683086
TI  - Phase synchronization of chaotic attractors with prescribed periodic signals.
AB  - Given a chaotic attractor in a dynamical system with dense periodic windows
      (i.e., structurally unstable), is it possible to find a periodic driver that will
      phase synchronize the chaotic attractor? We conjecture that the answer is
      typically yes, and we give an example for a funneling chaotic attractor in the
      Roessler system.

PMID- 14683087
TI  - Bursting and large-scale intermittency in turbulent convection with differential
      rotation.
AB  - The tilting mechanism, which generates differential rotation in two-dimensional
      turbulent convection, is shown to produce relaxation oscillations in the mean
      flow energy integral and bursts in the global fluctuation level, akin to Lotka
      Volterra oscillations. The basic reason for such behavior is the unidirectional
      and conservative transfer of kinetic energy from the fluctuating motions to the
      mean component of the flows, and its dissipation at large scales. Results from
      numerical simulations further demonstrate the intimate relation between these low
      frequency modulations and the large-scale intermittency of convective turbulence,
      as manifested by exponential tails in single-point probability distribution
      functions. Moreover, the spatio-temporal evolution of convective structures
      illustrates the mechanism triggering avalanche events in the transport process.
      The latter involves the overlap of delocalized mixing regions when the barrier to
      transport, produced by the mean component of the flow, transiently disappears.

PMID- 14683088
TI  - Variational principle for frozen-in vorticity interacting with sound waves.
AB  - General properties of conservative hydrodynamic-type models are treated from
      positions of the canonical formalism adopted for liquid continuous media. A
      variational formulation is found for motion and interaction of frozen-in
      localized vortex structures and acoustic waves in a special description where
      dynamical variables are, besides the Eulerian fields of the fluid density and the
      potential component of the canonical momentum, also the shapes of frozen-in lines
      of the generalized vorticity. This variational principle can serve as a basis for
      approximate dynamical models with reduced number of degrees of freedom.

PMID- 14683089
TI  - Plasma wakefield acceleration in self-ionized gas or plasmas.
AB  - Tunnel ionizing neutral gas with the self-field of a charged particle beam is
      explored as a possible way of creating plasma sources for a plasma wakefield
      accelerator [Bruhwiler et al., Phys. Plasmas (to be published)]. The optimal gas
      density for maximizing the plasma wakefield without preionized plasma is studied
      using the PIC simulation code OSIRIS [R. Hemker et al., in Proceeding of the
      Fifth IEEE Particle Accelerator Conference (IEEE, 1999), pp. 3672-3674]. To
      obtain wakefields comparable to the optimal preionized case, the gas density
      needs to be seven times higher than the plasma density in a typical preionized
      case. A physical explanation is given.

PMID- 14683090
TI  - Breather lattice and its stabilization for the modified Korteweg-de Vries
      equation.
AB  - We obtain an exact solution for the breather lattice solution of the modified
      Korteweg-de Vries equation. Numerical simulation of the breather lattice
      demonstrates its instability due to the breather-breather interaction. However,
      such multibreather structures can be stabilized through the concurrent
      application of ac driving and viscous damping terms.

PMID- 14683091
TI  - Comment on "Wealth condensation in Pareto macroeconomies".
AB  - In a recent study of the Pareto macroeconomy [Phys. Rev. E 65, 026102 (2002)], a
      surprising deviation to the power law distribution of the large wealths is
      reported. We comment that such a "corruption" phenomenon can be reproduced in a
      much simplified framework. The corruption disappears when the small wealths are
      further included in a mean-field treatment. The constraint of the total-wealth
      conservation leads to a cutoff in the power-law tail, in contrast to the
      prominent enhancement reported previously.

PMID- 14683092
TI  - Averaging for solitons with nonlinearity management.
AB  - We develop an averaging method for solitons of the nonlinear Schrodinger equation
      with a periodically varying nonlinearity coefficient, which is used to
      effectively describe solitons in Bose-Einstein condensates, in the context of the
      recently proposed technique of Feshbach resonance management. Using the derived
      local averaged equation, we study matter-wave bright and dark solitons and
      demonstrate a very good agreement between solutions of the averaged and full
      equations.

PMID- 14683093
TI  - Production of long-lived ultracold Li2 molecules from a Fermi gas.
AB  - We create weakly bound Li2 molecules from a degenerate two component Fermi gas by
      sweeping a magnetic field across a Feshbach resonance. The atom-molecule transfer
      efficiency can reach 85% and is studied as a function of magnetic field and
      initial temperature. The bosonic molecules remain trapped for 0.5 s and their
      temperature is within a factor of 2 from the Bose-Einstein condensation
      temperature. A thermodynamical model reproduces qualitatively the experimental
      findings.

PMID- 14683094
TI  - Pure gas of optically trapped molecules created from fermionic atoms.
AB  - We report on the production of a pure sample of up to 3 x 10(5) optically trapped
      molecules from a Fermi gas of 6Li atoms. The dimers are formed by three-body
      recombination near a Feshbach resonance. For purification, a Stern-Gerlach
      selection technique is used that efficiently removes all trapped atoms from the
      atom-molecule mixture. The behavior of the purified molecular sample shows a
      striking dependence on the applied magnetic field. For very weakly bound
      molecules near the Feshbach resonance, the gas exhibits a remarkable stability
      with respect to collisional decay.

PMID- 14683095
TI  - Quantum fluctuations of a vortex in an optical lattice.
AB  - Using a variational ansatz for the wave function of the Bose-Einstein condensate,
      we develop a quantum theory of vortices and quadrupole modes in a one-dimensional
      optical lattice. We study the coupling between the quadrupole modes and Kelvin
      modes, which turns out to be formally analogous to the theory of parametric
      processes in quantum optics. This leads to the possibility of squeezing vortices.
      We solve the quantum multimode problem for the Kelvin modes and quadrupole modes
      numerically and find properties that cannot be explained with a simple linear
      response theory.

PMID- 14683096
TI  - Decoherence-driven cooling of a degenerate spinor Bose gas.
AB  - We investigate the relationship between the coherence of a partially Bose
      condensed spinor gas and its temperature. We observe cooling of the normal
      component driven by decoherence as well as the effect of temperature on
      decoherence rates.

PMID- 14683097
TI  - Optically induced lensing effect on a Bose-Einstein condensate expanding in a
      moving lattice.
AB  - We report the experimental observation of a lensing effect on a Bose-Einstein
      condensate expanding in a moving 1D optical lattice. The effect of the periodic
      potential can be described by an effective mass dependent on the condensate
      quasimomentum. By changing the velocity of the atoms in the frame of the optical
      lattice, we induce a focusing of the condensate along the lattice direction. The
      experimental results are compared with the numerical predictions of an effective
      1D theoretical model. In addition, a precise band spectroscopy of the system is
      carried out by looking at the real-space propagation of the atomic wave packet in
      the optical lattice.

PMID- 14683098
TI  - Interference of atomic levels and superfluid-Mott insulator phase transitions in
      a two-component Bose-Einstein condensate.
AB  - The superfluid-Mott insulator phase transition in a Bose-Einstein condensate of
      neutral atoms with doubly degenerate internal ground states in an optical lattice
      is theoretically investigated. The optical lattice is created by two
      counterpropagating linearly polarized laser beams with the angle theta between
      the polarization vectors (lin-angle-lin configuration). The phase diagram of the
      system and the critical values of the parameters are worked out. It is shown that
      the sign of the detuning plays an important role and that there is a strong
      suppression of the Mott transition in the case of blue detuning. Varying the
      laser intensity and/or the angle theta one can manipulate the Mott insulator to
      superfluid quantum phase transition as well as prepare the condensate in
      physically distinguishable "ferromagnetic" and "antiferromagnetic" superfluid
      states.

PMID- 14683099
TI  - Gibbons-Hawking effect in the sonic de Sitter space-time of an expanding Bose
      Einstein-condensed gas.
AB  - We propose an experimental scheme to observe the Gibbons-Hawking effect in the
      acoustic analog of a (1+1)-dimensional de Sitter universe, produced in an
      expanding, cigar-shaped Bose-Einstein condensate. It is shown that a two-level
      system created at the center of the trap, an atomic quantum dot interacting with
      phonons, observes a thermal Bose distribution at the de Sitter temperature.

PMID- 14683100
TI  - All-optical realization of an atom laser.
AB  - We demonstrate an atom laser using all-optical techniques. A Bose-Einstein
      condensate of rubidium atoms is created by direct evaporative cooling in a
      quasistatic dipole trap realized with a single, tightly focused CO2-laser beam.
      An applied magnetic field gradient allows the formation of the condensate in a
      field-insensitive m(F)=0 spin projection only, which suppresses fluctuations of
      the chemical potential from stray magnetic fields. A collimated and monoenergetic
      beam of atoms is extracted from the Bose-Einstein condensate by continuously
      lowering the dipole trapping potential in a controlled way to form a novel type
      of atom laser.

PMID- 14683101
TI  - Dynamical robustness of Levy search strategies.
AB  - We study the role of dynamical constraints in the general problem of finding the
      best statistical strategy for random searching when the targets can be detected
      only in the limited vicinity of the searcher. We find that the optimal search
      strategy depends strongly on the delay time tau during which a previously visited
      site becomes unavailable. We also find that the optimal search strategy is always
      described for large step lengths l by a power-law distribution P(l) approximately
      l(-mu), with 1<mu(tau)</=2. Our findings appear to remain valid even if arbitrary
      energy costs of locomotion are considered.

PMID- 14683102
TI  - Low-energy X-ray standards from hydrogenlike pionic atoms.
AB  - We demonstrate the first step of a complete program, which consists in
      establishing an x-ray energy standard scale with the use of few-body atoms, in
      the few keV range. Light pionic and muonic atoms as well as one and two-electron
      ions from electron-cyclotron ion sources are used. The transition energies are
      calculable from quantum-electrodynamics, meaning that only a very limited subset
      need be measured and compared with theory, while providing a large number of
      standard lines. Here we show that circular transitions in pionic neon atoms,
      completely stripped from their electrons, reveal spectral lines which are narrow,
      symmetric, and well reproducible. We use these lines for the energy determination
      of transition energies in complex electronic systems, like the Kalpha(1,2)
      transitions in metallic Ti, which may serve as secondary standard.

PMID- 14683103
TI  - Determining neutrino mass from the cosmic microwave background alone.
AB  - Distortions of cosmic microwave background temperature and polarization maps
      caused by gravitational lensing, observable with high angular resolution and high
      sensitivity, can be used to measure the neutrino mass. Assuming two massless
      species and one with mass m(nu), we forecast sigma(m(nu))=0.15 eV from the Planck
      satellite and sigma(m(nu))=0.04 eV from observations with twice the angular
      resolution and approximately 20 times the sensitivity. A detection is likely at
      this higher sensitivity since the observation of atmospheric neutrino
      oscillations requires Deltam(2)(nu) greater, similar (0.04 eV)(2).

PMID- 14683104
TI  - Constraining the variation of fundamental constants using 18 cm OH lines.
AB  - We describe a new technique to estimate variations in the fundamental constants
      using 18 cm OH absorption lines, with the advantage that all lines arise in the
      same species, allowing a clean comparison between the measured redshifts. In
      conjunction with one additional transition, it is possible to simultaneously
      measure changes in alpha, g(p), and y identical with m(e)/m(p). We use the 1665
      and 1667 MHz line redshifts in conjunction with those of HI 21 cm and mm-wave
      molecular absorption in a gravitational lens at z approximately 0.68 to constrain
      changes in the three parameters over the redshift range 0<z less, similar 0.68.
      While the constraints are relatively weak ( less, similar 1 part in 10(3)), this
      is the first simultaneous constraint on the variation of all three parameters.
      Either one (or more) of alpha, g(p), and y must vary with cosmological time or
      there must be systematic velocity offsets between the OH, HCO+, and HI absorbing
      clouds.

PMID- 14683105
TI  - New global defect structures.
AB  - We investigate the presence of defects in systems described by real scalar field
      in (D,1) spacetime dimensions. We show that when the potential assumes specific
      form, there are models which support stable global defects for D arbitrary. We
      also show how to find first-order differential equations that solve the equations
      of motion, and how to solve models in D dimensions via soluble problems in D=1.
      We illustrate the procedure examining specific models and finding explicit
      solutions.

PMID- 14683106
TI  - Possible supersymmetric solution to the discrepancy between B-->phiK(S) and B-
      >eta'K(S) CP asymmetries.
AB  - We present a possible supersymmetric solution to the discrepancy between the
      observed mixing CP asymmetries in B-->phiK(S) and B-->eta(')K(S). We show that,
      due to the different parity in the final states of these processes, their
      supersymmetric contributions from the R sector have opposite signs, which
      naturally leads to S(phiK(S)) not equal Seta(')(K(S)). We also consider the
      proposed mechanisms to solve the puzzle of the observed large branching ratio of
      B-->eta'K and their impact on Seta(')(K(S)).

PMID- 14683108
TI  - Evidence for B-->phiphiK.
AB  - We report evidence for the decay mode B-->phiphiK based on an analysis of 78 fb(
      1) of data collected with the Belle detector at KEKB. This is the first example
      of a b-->sssss transition. The branching fraction for this decay is measured to
      be B(B+/--->phiphiK+/-)=(2.6(+1.1)(-0.9)+/-0.3)x10(-6) for a phiphi invariant
      mass below 2.85 GeV/c(2). Results for other related charmonium decay modes are
      also reported.

PMID- 14683111
TI  - Electromagnetic Meissner effect in spin-one color superconductors.
AB  - It is shown that color-superconducting quark matter, where quarks of the same
      flavor form Cooper pairs with spin one, exhibits an electromagnetic Meissner
      effect. This is in contrast to spin-zero color superconductors where Cooper pairs
      consist of quarks with different flavors.

PMID- 14683112
TI  - Phase space manipulation of cold free radical OH molecules.
AB  - We report bunching, slowing, and acceleration of a supersonically cooled beam of
      diatomic hydroxyl radicals (OH). In situ observation of laser-induced
      fluorescence along the beam propagation path allows for detailed characterization
      of longitudinal phase-space manipulation of OH molecules through the Stark effect
      by precisely sequenced inhomogeneous electric fields.

PMID- 14683113
TI  - Precision frequency measurement of visible intercombination lines of strontium.
AB  - We report the direct frequency measurement of the visible 5s(2) 1S0-5s5p 3P1
      intercombination line of strontium that is considered a possible candidate for a
      future optical-frequency standard. The frequency of a cavity-stabilized laser is
      locked to the saturated fluorescence in a thermal Sr atomic beam and is measured
      with an optical-frequency comb generator referenced to the SI second through a
      global positioning system signal. The 88Sr transition is measured to be at 434
      829 121 311 (10) kHz. We measure also the 88Sr-86Sr isotope shift to be 163 817.4
      (0.2) kHz.

PMID- 14683114
TI  - High-precision molecular wave-packet interferometry with HgAr dimers.
AB  - Molecular wave-packet (WP) interferometry has been demonstrated in the A
      electronic state of the HgAr van der Waals complex with two time-delayed UV fs
      pulses at 254 nm. The interferograms of three vibrational levels in the WP's
      display almost 100% fringe contrast as a function of the interpulse delay tau,
      which is tuned with sub-10 as stability and resolution. It is clearly observed
      that the three interferograms show their dephasing and rephasing within a single
      vibrational period, allowing us to prepare arbitrary relative populations of the
      three levels by adjusting a single parameter tau.

PMID- 14683115
TI  - Enhancing acceleration radiation from ground-state atoms via cavity quantum
      electrodynamics.
AB  - When ground-state atoms are accelerated through a high Q microwave cavity,
      radiation is produced with an intensity which can exceed the intensity of Unruh
      acceleration radiation in free space by many orders of magnitude. The reason is a
      strong nonadiabatic effect at cavity boundaries and its interplay with the
      standard Unruh effect. The cavity field at steady state is still described by a
      thermal density matrix under most conditions. However, under some conditions gain
      is possible, and when the atoms are injected in a regular fashion, squeezed
      radiation can be produced.

PMID- 14683109
TI  - Midrapidity neutral-pion production in proton-proton collisions at square root s
      = 200 GeV.
AB  - The invariant differential cross section for inclusive neutral-pion production in
      p+p collisions at sqrt[s]=200 GeV has been measured at midrapidity (|eta|<0.35)
      over the range 1<p(T) less, similar 14 GeV/c by the PHENIX experiment at the
      Relativistic Heavy Ion Collider. Predictions of next-to-leading order
      perturbative QCD calculations are consistent with these measurements. The
      precision of our result is sufficient to differentiate between prevailing gluon
      to-pion fragmentation functions.

PMID- 14683116
TI  - State selective charge transfer cross sections for Na+ with excited rubidium: a
      unique diagnostic of the population dynamics of a magneto-optical trap.
AB  - It is shown how the newly developed technique of magneto-optical-trap recoil-ion
      momentum spectroscopy can be used to measure the temporal evolution of excited
      state fraction in such a trap. In this case, the fraction of atoms in a 5p state
      is measured. The technique can be generalized to allow the measurement of more
      complicated systems, e.g., a Rb sample having a mixture of 5s, 5p, 4d, and
      Rydberg states.

PMID- 14683117
TI  - Oxygen and silver clusters: transition from chemisorption to oxidation.
AB  - We use the adsorption probabilities of molecular nitrogen and oxygen to study the
      physi- and chemisorption on small silver particles. The physisorption of nitrogen
      is governed by the structure of the particle surface. The sticking of oxygen
      additionally involves the electronic configuration of the metal cluster. At 77 K
      molecular oxygen sticks chemisorbed to the particles with a transfer of one
      electron. At temperatures above 105 K the chemisorption transforms into
      oxidation, invoking the dissociation of the oxygen molecule and the loss of a
      single oxygen atom.

PMID- 14683118
TI  - Optical control of the rotational angular momentum of a molecular Rydberg wave
      packet.
AB  - An intuitive scheme for controlling the rotational quantum state of a Rydberg
      molecule is demonstrated experimentally. We determine the accumulated phase
      difference between the various components of a molecular electron wave packet,
      and then employ a sequence of phase-locked optical pulses to selectively enhance
      or depopulate specific rotational states. The angular momentum composition of the
      resulting wave packet, and the efficiency of the control scheme, is determined by
      calculating the multipulse response of the time-dependent Rydberg populations.

PMID- 14683119
TI  - Characterization of a chaotic optical field using a high-gain, self-amplified
      free-electron laser.
AB  - We report on a characterization of the chaotic optical field from a high-gain,
      self-amplified spontaneous-emission (SASE) free-electron laser. The temporal
      structure of the amplitude and phase are measured in a single-shot mode, with a
      resolution well below the coherence length, and the statistics over multiple
      pulses is determined. The measurement is in excellent quantitative agreement with
      the prediction based on analysis of random noise, and further verifies the
      chaotic nature of the SASE optical field.

PMID- 14683120
TI  - Ultrahigh harmonics from laser-assisted ion-atom collisions.
AB  - We present a theoretical analysis of high-order harmonic generation from ion-atom
      collisions in the presence of linearly polarized intense laser pulses. Photons
      with frequencies significantly higher than in standard atomic high-harmonic
      generation are emitted. These harmonics are due to two different mechanisms: (i)
      collisional electron capture and subsequent laser-driven transfer of an electron
      between projectile and target atom; (ii) reflection of a laser-driven electron
      from the projectile leading to recombination at the parent atom.

PMID- 14683121
TI  - Inhibiting the onset of the three-photon destructive interference in ultraslow
      propagation-enhanced four-wave mixing with dual induced transparency.
AB  - We propose a dual electromagnetically induced transparency (EIT) based multiwave
      mixing scheme that retains the significantly enhanced conversion efficiency
      enabled by ultraslow propagation of pump waves, yet is also capable of inhibiting
      and delaying the onset of the detrimental three-photon destructive interference
      that limits the further growth of the four-wave mixing (FWM) field. We show that
      the new scheme exhibits a wave-matching condition that is fundamentally different
      from the conventional FWM without EIT, and the efficient generation of the mixing
      wave is not critically dependent upon the FWM detuning to achieve constructive
      interference as required in the conventional FWM. These are significant steps
      forward in enabling applications of ultraslow wave nonlinear optics.

PMID- 14683122
TI  - New parametric scattering in photorefractive Sr0.61Ba0.39Nb2O6:Cr.
AB  - A new class of light-induced parametric scattering, not included in the
      conventional model, has been discovered in photorefractive
      Sr(0.61)Ba(0.39)Nb(2)O(6):Cr illuminated by two coherent beams. A novel model of
      multiwave mixing of coherent noise and transmitted light is developed to explain
      the new scattering phenomena. The model includes all known types and predicts a
      multitude of new types of parametric scattering. Generalized phase-matching
      conditions for parametric scattering in photorefractive crystals are proposed.

PMID- 14683123
TI  - Green function retrieval and time reversal in a disordered world.
AB  - We apply the theory of multiple wave scattering to two contemporary, related
      topics: imaging with diffuse correlations and stability of the time reversal of
      diffuse waves, using equipartition, coherent backscattering, and frequency
      speckles as fundamental concepts.

PMID- 14683124
TI  - Experimental observation of multifrequency patterns in arrays of coupled
      nonlinear oscillators.
AB  - Frequency-related oscillations in coupled oscillator systems, in which one or
      more oscillators oscillate at different frequencies than the other oscillators,
      have been studied using group theoretical methods by Armbruster and Chossat
      [Phys. Lett. A 254, 269 (1999)] and more recently by Golubitsky and Stewart [in
      Geometry, Mechanics, and Dynamics, edited by P. Newton, P. Holmes, and A.
      Weinstein (Springer, New York, 2002), p. 243]. We demonstrate, experimentally,
      via electronic circuits, the existence of frequency-related oscillations in a
      network of two arrays of N oscillators, per array, coupled to one another. Under
      certain conditions, one of the arrays can be induced to oscillate at N times the
      frequency of the other array. This type of behavior is different from the one
      observed in a driven system because it is dictated mainly by the symmetry of the
      coupled system.

PMID- 14683125
TI  - Dynamics of axial segregation and coarsening of dry granular materials and
      slurries in circular and square tubes.
AB  - We study segregation and coarsening dynamics of dry granular materials and
      slurries in tubes with circular and square cross sections. Space-time plots show
      key differences between the four cases, including band splitting and wave
      formation, depending upon the rotational speed. However, the fraction of the
      surface occupied by bands of small-rich particles is nearly constant in all
      experiments, leading to quasi-1D behavior, and the rate of coarsening, when it
      occurs, is logarithmic in all cases. Coarsening rates are very similar except in
      the case with the longest development time.

PMID- 14683126
TI  - Pseudo angular momentum and topological charge conservation for nonlinear
      acoustical vortices.
AB  - We study acoustical vortices (AVs) and their connection with optical vortices
      (OVs). We show that AVs and OVs have the same properties if the concept of
      pseudomomentum is used. Radiation stress and conservation of topological charge
      are obtained with the pseudomomentum rule. In a weak nonlinear regime, the
      conservation of pseudo angular momentum imposes a linear increase of the
      topological charge with the harmonic order. This last result is experimentally
      verified.

PMID- 14683107
TI  - Observation of a significant excess of pi0pi0 events in B meson decays.
AB  - We present a study of the decay B0-->pi(0)pi(0) based on a sample of 124 x 10(6)
      BB pairs recorded by the BABAR detector at the PEP-II asymmetric-energy B Factory
      at SLAC. We observe 46+/-13+/-3 events, where the first error is statistical and
      the second is systematic, corresponding to a significance of 4.2 standard
      deviations including systematic uncertainties. We measure the branching fraction
      B(B0-->pi(0)pi(0))=(2.1+/-0.6+/-0.3)x10(-6), averaged over B0 and B(0) decays.

PMID- 14683127
TI  - Anisotropy and universality: the Oslo model, the rice pile experiment, and the
      quenched Edwards-Wilkinson equation.
AB  - We show that any amount of anisotropy moves the Oslo model to another known
      universality class, the exponents of which can be derived exactly. This amounts
      to an exact solution of the quenched Edwards-Wilkinson equation with a drift
      term. We argue that anisotropy is likely to be experimentally relevant and may
      explain why consistent exponents have not been extracted in the rice pile
      experiments.

PMID- 14683110
TI  - Measurement of prompt charm meson production cross sections in pp collisions at
      square root s = 1.96 TeV.
AB  - We report on measurements of differential cross sections dsigma/dp(T) for prompt
      charm meson production in ppmacr; collisions at sqrt[s]=1.96 TeV using 5.8+/-0.3
      pb(-1) of data from the CDF II detector at the Fermilab Tevatron. The data are
      collected with a new trigger that is sensitive to the long lifetime of hadrons
      containing heavy flavor. The charm meson cross sections are measured in the
      central rapidity region |y|</=1 in four fully reconstructed decay modes: D0-->K
      pi(+), D(*+)-->D0pi(+), D+-->K-pi(+)pi(+), D(+)(s)-->phipi(+), and their charge
      conjugates. The measured cross sections are compared to theoretical calculations.

PMID- 14683128
TI  - Drifting convection cells in rotating fluid layers heated from below.
AB  - It is shown that hexagonal convection cells in a rotating horizontal fluid layer
      heated from below will in general exhibit a drift in contrast to convection rolls
      except in the case of a vertical axis of rotation. The direction of the drift is
      prograde (retrograde) for cells with rising (descending) motion in the center of
      the convection cell. In addition a mean flow generated by convection is derived.
      An application to solar convection is discussed.

PMID- 14683129
TI  - Scaling of the turbulence transition threshold in a pipe.
AB  - We report the results of an experimental investigation of the transition to
      turbulence in a pipe over approximately an order of magnitude range in the
      Reynolds number Re. A novel scaling law is uncovered using a systematic
      experimental procedure which permits contact to be made with modern theoretical
      thinking. The principal result we uncover is a scaling law which indicates that
      the amplitude of perturbation required to cause transition scales as O(Re-1).

PMID- 14683130
TI  - Observation of helicity-induced Alfven eigenmodes in large-helical-device plasmas
      heated by neutral-beam injection.
AB  - The helicity-induced Alfven eigenmodes (HAEs) with the toroidal mode number n=2
      and 3 are observed for the first time in the Large Helical Device plasmas heated
      by neutral beam injection. The observed mode frequency is about 8 times higher
      than that of the observed toroidicity-induced Alfven eigenmodes, and is
      proportional to the Alfven velocity. The modes are excited when the ratio of the
      beam velocity to the Alfven velocity exceeds about unity. The frequency lies just
      above the lower bound of the HAE gap in the plasma edge region of rho>0.7 (rho:
      normalized minor radius).

PMID- 14683131
TI  - Observations of electron diffusion regions at the subsolar magnetopause.
AB  - Electric and magnetic field observations on the Polar satellite at the subsolar
      magnetopause show that the magnetopause current is often striated. The largest of
      the resulting current channels are interpreted as electron diffusion regions
      because their widths are several electron skin depths and the electron flow U(e)
      within them does not satisfy E-->+U-->(e)xB-->=0. The data suggest that the
      magnetopause contains many such electron diffusion regions and that they are
      required because E-->xB-->/B(2) drifting electrons cannot carry the large
      filamentary currents imposed on the local plasma. The most probable
      interpretation of E-->+U-->(e)xB--> not equal 0 is that the pressure term on the
      right side of the generalized Ohm's law balances this inequality.

PMID- 14683132
TI  - Unusual thermal diffusion in polymer solutions.
AB  - Thermal diffusion forced Rayleigh scattering results on thermal diffusion of
      poly(ethylene oxide) (PEO) in ethanol/water mixtures are presented. In water-rich
      solvent mixtures, PEO is found to migrate towards regions of lower temperature.
      This is typical for polymer solutions and corresponds to a positive Soret
      coefficient of PEO. In solvent mixtures with low water content, however, the
      polymer is found to migrate towards higher temperatures, corresponding to a
      negative Soret coefficient of PEO in ethanol-rich solutions. To our knowledge,
      this is the first observed sign change of the Soret coefficient of a polymer in
      solution. We also present a simple lattice model for the polymer solvent system
      and calculate Soret coefficients with statistical mechanics methods. The
      calculated values agree qualitatively with the experimental results.

PMID- 14683133
TI  - Radiation enhanced silicon self-diffusion and the silicon vacancy at high
      temperatures.
AB  - We report proton radiation enhanced self-diffusion (RESD) studies on Si-isotope
      heterostructures. Self-diffusion experiments under irradiation were performed at
      temperatures between 780 degrees C and 872 degrees C for various times and proton
      fluxes. Detailed modeling of RESD provides direct evidence that vacancies at high
      temperatures diffuse with a migration enthalpy of H(m)(V)=(1.8+/-0.5) eV
      significantly more slowly than expected from their diffusion at low temperatures,
      which is described by H(m)(V)<0.5 eV. We conclude that this diffusion behavior is
      a consequence of the microscopic configuration of the vacancy whose entropy and
      enthalpy of migration increase with increasing temperature.

PMID- 14683134
TI  - Instabilities in complex mixtures with a large number of components.
AB  - Inside living cells are complex mixtures of thousands of components. It is
      hopeless to try to characterize all the individual interactions in these
      mixtures. Thus, we develop a statistical approach to approximating them, and
      examine the conditions under which the mixtures phase separate. The approach
      approximates the matrix of second-virial coefficients of the mixture by a random
      matrix, and determines the stability of the mixture from the spectrum of such
      random matrices.

PMID- 14683135
TI  - Excitonic absorption above the Mott transition in Si.
AB  - We present experimental evidence for the existence of excitonic states above the
      excitonic Mott transition in both highly doped and highly excited silicon.
      Previous limitations to resolve the fundamental absorption edge of Si at dense
      carrier plasmas are overcome employing a novel spatially and time-resolved
      spectroscopy. We show that the obtained density dependent excess absorption at 75
      K represents an excitonic enhancement effect, which is attributed to persisting
      many-body interactions.

PMID- 14683136
TI  - Nontrivial fixed point in a twofold orbitally degenerate Anderson impurity model.
AB  - We study a twofold orbitally degenerate Anderson impurity model which shows a
      nontrivial fixed point similar to that of the two-impurity Kondo model, but
      remarkably more robust, as it can only be destabilized by orbital- or gauge
      symmetry breaking. The impurity model is interesting per se, but here our
      interest is rather in the possibility that it might be representative of a
      strongly correlated lattice model close to a Mott transition. We argue that this
      lattice model should unavoidably encounter the nontrivial fixed point just before
      the Mott transition and react to its instability by spontaneous generation of an
      orbital, spin-orbital or superconducting order parameter.

PMID- 14683137
TI  - Diluted II-VI oxide semiconductors with multiple band gaps.
AB  - We report the realization of a new mult-band-gap semiconductor. Zn(1-y)Mn(y)OxTe1
      x alloys have been synthesized using the combination of oxygen ion implantation
      and pulsed laser melting. Incorporation of small quantities of isovalent oxygen
      leads to the formation of a narrow, oxygen-derived band of extended states
      located within the band gap of the Zn(1-y)Mn(y)Te host. When only 1.3% of Te
      atoms are replaced with oxygen in a Zn0.88Mn0.12Te crystal the resulting band
      structure consists of two direct band gaps with interband transitions at
      approximately 1.77 and 2.7 eV. This remarkable modification of the band structure
      is well described by the band anticrossing model. With multiple band gaps that
      fall within the solar energy spectrum, Zn(1-y)Mn(y)OxTe1-x is a material
      perfectly satisfying the conditions for single-junction photovoltaics with the
      potential for power conversion efficiencies surpassing 50%.

PMID- 14683138
TI  - Indium square root 7 x square root 3 on Si(111): a nearly free electron metal in
      two dimensions.
AB  - We present measurements of the Fermi surface and underlying band structure of a
      single layer of indium on Si(111) with square root 7 x square root 3 periodicity.
      Electrons from both indium valence electrons and silicon dangling bonds
      contribute to a nearly free, two-dimensional metal on a pseudo-4-fold lattice,
      which is almost completely decoupled at the Fermi level from the underlying
      hexagonal silicon lattice. The mean free path inferred from our data is quite
      long, suggesting the system might be a suitable model for studying the ground
      state of two-dimensional metals.

PMID- 14683139
TI  - Field-induced quantum critical point in CeCoIn5.
AB  - The resistivity of the heavy-fermion superconductor CeCoIn5 was measured as a
      function of temperature, down to 25 mK and in magnetic fields of up to 16 T
      applied perpendicular to the basal plane. With increasing field, we observe a
      suppression of the non-Fermi liquid behavior, rho approximately T, and the
      development of a Fermi liquid state, with its characteristic rho=rho(0)+AT2
      dependence. The field dependence of the T2 coefficient shows critical behavior
      with an exponent of 1.37. This is evidence for a field-induced quantum critical
      point (QCP), occurring at a critical field which coincides, within experimental
      accuracy, with the superconducting critical field H(c2). We discuss the relation
      of this field-tuned QCP to a change in the magnetic state, seen as a change in
      magnetoresistance from positive to negative, at a crossover line that has a
      common border with the superconducting region below approximately 1 K.

PMID- 14683140
TI  - High temperature gate control of quantum well spin memory.
AB  - Time-resolved optical measurements in (110)-oriented GaAs/AlGaAs quantum wells
      show a tenfold increase of the spin-relaxation rate as a function of applied
      electric field from 20 to 80 kV cm(-1) at 170 K and indicate a similar variation
      at 300 K, in agreement with calculations based on the Rashba effect. Spin
      relaxation is almost field independent below 20 kV cm(-1) reflecting quantum well
      interface asymmetry. The results indicate the achievability of a voltage-gateable
      spin-memory time longer than 3 ns simultaneously with a high electron mobility.

PMID- 14683141
TI  - Inhomogeneous ferromagnetism and unconventional charge dynamics in disordered
      double exchange magnets.
AB  - We solve the double exchange model in the presence of arbitrary substitutional
      disorder by using a self-consistently generated effective Hamiltonian for the
      spin degrees of freedom. The magnetic properties are studied through classical
      Monte Carlo while the effective exchange, D(ij), is calculated by solving the
      disordered fermion problem, and renormalized self-consistently with increasing
      temperature. We present results on the conductivity, magnetoresistance, optical
      response, and "real space" structure of the inhomogeneous ferromagnetic state,
      and compare our results with charge dynamics in disordered La1-xSrxMnO3. The
      large sizes, O(10(3)), accessible within our method allows a complete, controlled
      calculation on the disordered strongly interacting problem.

PMID- 14683142
TI  - Electrical detection of spin coherence in silicon.
AB  - Experimental evidence is presented showing that photocurrents in silicon can be
      used as highly sensitive readout probes for coherent spin states of localized
      electrons, the prime candidates for quantum bits in various semiconductor based
      quantum computer concepts. Conduction electrons are subjected to fast Rabi
      oscillation induced by means of pulsed electron spin resonance. The collective
      spin motion of the charge carrier ensemble is reflected by a spin-dependent
      recombination rate and therefore by the sample conductivity. Because of
      inhomogeneities, the Rabi oscillation dephases rapidly. However, a microwave
      induced rephasing is possible causing an echo effect whose intensity contains
      information about the charge carrier spin state and the coherence decay.

PMID- 14683143
TI  - Transport properties of granular metals at low temperatures.
AB  - We investigate transport in a granular metallic system at large tunneling
      conductance between the grains, g(T)>>1. We show that at low temperatures,
      T</=g(T)delta, where delta is the mean energy level spacing in a single grain,
      the coherent electron motion at large distances dominates the physics, contrary
      to the high-temperature (T>g(T)delta) behavior where conductivity is controlled
      by the scales of the order of the grain size. In three dimensions we predict the
      metal-insulator transition at the bare tunneling conductance
      g(C)(T)=(1/6pi)ln((E(C)/delta), where E(C) is the charging energy of a single
      grain. Corrections to the density of states of granular metals due to the
      electron-electron interaction are calculated. Our results compare favorably with
      the logarithmic dependence of resistivity in the high-T(c) cuprate
      superconductors indicating that these materials may have a granular structure.

PMID- 14683144
TI  - Controlling a mesoscopic spin environment by quantum bit manipulation.
AB  - We present a unified description of cooling and manipulation of a mesoscopic bath
      of nuclear spins via coupling to a single quantum system of electronic spin
      (quantum bit). We show that a bath cooled by the quantum bit rapidly saturates.
      Although the resulting saturated states of the spin bath ("dark states")
      generally have low degrees of polarization and purity, their symmetry properties
      make them a valuable resource for the coherent manipulation of quantum bits.
      Specifically, we demonstrate that the dark states of nuclear ensembles can be
      used to coherently control the system-bath interaction and to provide a robust,
      long-lived quantum memory for qubit states.

PMID- 14683145
TI  - Imaging fractal conductance fluctuations and scarred wave functions in a quantum
      billiard.
AB  - We present scanning-probe images and magnetic-field plots which reveal fractal
      conductance fluctuations in a quantum billiard. The quantum billiard is drawn and
      tuned using erasable electrostatic lithography, where the scanning probe draws
      patterns of surface charge in the same environment used for measurements. A
      periodicity in magnetic field, which is observed in both the images and plots,
      suggests the presence of classical orbits. Subsequent high-pass filtered high
      resolution images resemble the predicted probability density of scarred wave
      functions, which describe the classical orbits.

PMID- 14683146
TI  - Photocurrent, rectification, and magnetic field symmetry of induced current
      through quantum dots.
AB  - We report mesoscopic dc current generation in an open chaotic quantum dot with ac
      excitation applied to one of the shape-defining gates. For excitation frequencies
      large compared to the inverse dwell time of electrons in the dot (i.e., GHz), we
      find mesoscopic fluctuations of induced current that are fully asymmetric in the
      applied perpendicular magnetic field, as predicted by recent theory. Conductance,
      measured simultaneously, is found to be symmetric in field. In the adiabatic
      (i.e., MHz) regime, in contrast, the induced current is always symmetric in
      field, suggesting its origin is mesoscopic rectification.

PMID- 14683147
TI  - Superconductivity in doped sp3 semiconductors: the case of the clathrates.
AB  - We present a joint experimental and theoretical study of the superconductivity in
      doped silicon clathrates. The critical temperature in Ba(8)@Si-46 is shown to
      strongly decrease with applied pressure. These results are corroborated by ab
      initio calculations using MacMillan's formulation of the BCS theory with the
      electron-phonon coupling constant lambda calculated from perturbative density
      functional theory. Further, the study of I(8)@Si-46 and of gedanken pure silicon
      diamond and clathrate phases doped within a rigid-band approach show that the
      superconductivity is an intrinsic property of the sp(3) silicon network. As a
      consequence, carbon clathrates are predicted to yield large critical temperatures
      with an effective electron-phonon interaction much larger than in C60.

PMID- 14683148
TI  - Phase separation in asymmetrical fermion superfluids.
AB  - Motivated by recent developments on cold atom traps and high density QCD we
      consider fermionic systems composed of two particle species with different
      densities. We argue that a mixed phase composed of normal and superfluid
      components is the energetically favored ground state. We suggest how this phase
      separation can be used as a probe of fermion superfluidity in atomic traps.

PMID- 14683149
TI  - Probing the superconducting gap symmetry of PrOs4Sb12: a penetration depth study.
AB  - We report measurements of the magnetic penetration depth lambda in single
      crystals of PrOs4Sb12 down to 0.1 K, with the ac field applied along the a, b,
      and c directions. In all three field orientations, lambda approximately T2 and
      superfluid density rho(s) approximately T2 for T<0.3T(c). Data are best fit by
      the 3He A-phase-like gap with multidomains, each having two point nodes along a
      cube axis, and parameter Delta(0)(0)/k(B)T(c)=2.6, suggesting that PrOs4Sb12 is a
      strong-coupling superconductor with two point nodes on the Fermi surface. We also
      confirm the double transitions at 1.75 and 1.85 K seen in other measurements.

PMID- 14683150
TI  - Reentrant behavior of the phase stiffness in Josephson junction arrays.
AB  - The phase diagram of a 2D Josephson junction array with large substrate
      resistance, described by a quantum XY model, is studied by means of Fourier path
      integral Monte Carlo. A genuine Berezinskii-Kosterlitz-Thouless transition is
      found up to a threshold value g( small star, filled ) of the quantum coupling,
      beyond which no phase coherence is established. Slightly below g( small star,
      filled ) the phase stiffness shows a reentrant behavior with temperature, in
      connection with a low-temperature disappearance of the superconducting phase,
      driven by strong nonlinear quantum fluctuations.

PMID- 14683151
TI  - Tunable magnetic relaxation mechanism in magnetic nanoparticles.
AB  - We investigate theoretically the magnetization dynamics of a conducting magnetic
      nanoparticle weakly coupled to source and drain electrodes, under the assumption
      that all relaxation comes from exchange of electrons with the electrodes. In the
      regime of sequential tunneling, the magnetization dynamics is characterized by a
      relaxation time t(1), which strongly depends on temperature, bias voltage, and
      gate voltage. While a direct measure of a nanoparticle magnetization might be
      difficult, we find that t(1) can be determined through a time resolved transport
      measurement. For a suitable choice of gate voltage and bias voltage, the
      magnetization performs a bias-driven Brownian motion regardless of the presence
      of anisotropy.

PMID- 14683152
TI  - Kondo effect in the presence of itinerant-electron ferromagnetism studied with
      the numerical renormalization group method.
AB  - The Kondo effect in quantum dots (QDs)-artificial magnetic impurities-attached to
      ferromagnetic leads is studied with the numerical renormalization group method.
      It is shown that the QD level is spin split due to the presence of ferromagnetic
      electrodes, leading to a suppression of the Kondo effect. We find that the Kondo
      effect can be restored by compensating this splitting with a magnetic field.
      Although the resulting Kondo resonance then has an unusual spin asymmetry with a
      reduced Kondo temperature, the ground state is still a locally screened state,
      describable by Fermi liquid theory and a generalized Friedel sum rule, and
      transport at zero temperature is spin independent.

PMID- 14683153
TI  - Superradiance in molecular H aggregates.
AB  - Direct evidence of superradiance from an organic semiconductor (quaterthiophene)
      whose molecules are arranged in a H aggregate fashion, is reported. Time resolved
      photoluminescence measurements show a linear correlation between the radiative
      lifetime (tau(rad)) of the purely electronic exciton recombination and the
      inverse of the number (N(C)) of the coherently emitting dipoles, i.e., tau(rad)
      proportional, variant 1/N(C). These data support the recently developed
      theoretical models describing the optical properties of H aggregates of rodlike
      molecules with a nonvanishing component of the perpendicular molecular transition
      dipole moment.

PMID- 14683154
TI  - Real-time capturing of the nuclear wave-packet shape in self-trapped excitons.
AB  - We measured the time evolutions of the luminescence spectra in a quasi-1D halogen
      bridged platinum complex [Pt(en)(2)][Pt(en)(2)Br(2)](ClO4)(4) with a 50 fs
      resolution up-conversion spectroscopy and succeeded in real-time visualization of
      the shape of the wave packet (WP) propagating on the adiabatic potential surface
      of a self-trapped exciton. The behavior of the WP is in excellent agreement with
      a calculation based on a harmonic oscillator. We have found that the damping of
      the WP oscillation is highly nonexponential.

PMID- 14683155
TI  - Solid state solvation in amorphous organic thin films.
AB  - The photoluminescence (PL) of the red laser dye DCM2, doped into blended thin
      films of polystyrene (PS) and the polar small molecule camphoric anhydride (CA),
      redshifts as the CA concentration increases. The DCM2 PL peaks at 2.20 eV
      (lambda=563 nm) for pure PS films and shifts to 2.05 eV (lambda=605 nm) for films
      with 24.5% CA (by mass). The capacitively measured electronic permittivity also
      increases from epsilon=2.4 to epsilon=5.6 with CA concentration. These results
      are consistent with the theory of solvatochromism developed for organic molecules
      in liquid solvents. To our knowledge, this work is the first application of a
      quantitative theory of solvation to organic molecules in amorphous thin films
      with continuously controllable permittivity, and demonstrates that "solid state
      solvation" can be used to predictably tune exciton energies in organic thin film
      structures.

PMID- 14683156
TI  - Broken time reversal of light interaction with planar chiral nanostructures.
AB  - We report unambiguous experimental evidence of broken time-reversal symmetry for
      the interaction of light with an artificial nonmagnetic material. Polarized color
      images of planar chiral gold-on-silicon nanostructures consisting of arrays of
      gammadions show intriguing and unusual symmetry: structures, which are
      geometrically mirror images, lose their mirror symmetry in polarized light. The
      symmetry of images can be described only in terms of antisymmetry (black-and
      white symmetry) appropriate to a time-odd process. The effect results from a
      transverse chiral nonlocal electromagnetic response of the structure and has some
      striking resemblance with the expected features of light scattering on anyon
      matter.

PMID- 14683157
TI  - Self-organized nanogratings in glass irradiated by ultrashort light pulses.
AB  - Periodic nanostructures are observed inside silica glass after irradiation by a
      focused beam of a femtosecond Ti:sapphire laser. Backscattering electron images
      of the irradiated spot reveal a periodic structure of stripelike regions of
      approximately 20 nm width with a low oxygen concentration, which are aligned
      perpendicular to the laser polarization direction. These are the smallest
      embedded structures ever created by light. The period of self-organized grating
      structures can be controlled from approximately 140 to 320 nm by the pulse energy
      and the number of irradiated pulses. The phenomenon is interpreted in terms of
      interference between the incident light field and the electric field of the bulk
      electron plasma wave, resulting in the periodic modulation of electron plasma
      concentration and the structural changes in glass.

PMID- 14683158
TI  - Field cooled and zero field cooled 207Pb NMR and the local structure of relaxor
      PbMg1/3Nb2/3O3.
AB  - An isotropic 207Pb NMR spectrum corresponding to the glassy matrix with spherical
      shell type Pb shifts from the cubic sites, as well as an anisotropic spectral
      component corresponding to polar nanoclusters with a Pb shift parallel to the
      [111] direction, have been observed in a PbMg(1/3)Nb(2/3)O3 (PMN) single crystal.
      This represents a microscopic confirmation of the model of relaxors first
      proposed by Burns and Dacol. A sudden increase in the intensity of the
      anisotropic cluster line is seen for electric fields larger than the critical
      field around 210 K. This demonstrates the occurrence of an orientational
      percolation type transition to the field-induced ferroelectric phase with about
      50% of the Pb nuclei still remaining in the spherical glass matrix. A similar
      though smaller increase of the intensity of this line is also seen in the zero
      field cooled data, demonstrating that relaxor PMN is an incipient ferroelectric.

PMID- 14683159
TI  - Efficient immunization strategies for computer networks and populations.
AB  - We present an effective immunization strategy for computer networks and
      populations with broad and, in particular, scale-free degree distributions. The
      proposed strategy, acquaintance immunization, calls for the immunization of
      random acquaintances of random nodes (individuals). The strategy requires no
      knowledge of the node degrees or any other global knowledge, as do targeted
      immunization strategies. We study analytically the critical threshold for
      complete immunization. We also study the strategy with respect to the susceptible
      infected-removed epidemiological model. We show that the immunization threshold
      is dramatically reduced with the suggested strategy, for all studied cases.

PMID- 14683160
TI  - Depletion forces in nonequilibrium.
AB  - The concept of effective depletion forces between two fixed big colloidal
      particles in a bath of small particles is generalized to a nonequilibrium
      situation where the bath of small Brownian particles is flowing around the big
      particles with a prescribed velocity. In striking contrast to the equilibrium
      case, the nonequilibrium forces violate Newton's third law; they are
      nonconservative and strongly anisotropic, featuring both strong attractive and
      repulsive domains.

PMID- 14683161
TI  - Comment on "Left-handed-media simulation and transmission of EM waves in
      subwavelength split-ring-resonator-loaded metallic waveguides".

PMID- 14683163
TI  - Long-range nature of feshbach molecules in bose-einstein condensates.
AB  - We discuss the long-range nature of the molecules produced in recent experiments
      on molecular Bose-Einstein condensation. The properties of these molecules depend
      on the full two-body Hamiltonian and not just on the states of the system in the
      absence of interchannel couplings. The very long-range nature of the state is
      crucial to the efficiency of production in the experiments. Our many-body
      treatment of the gas accounts for the full binary physics and describes properly
      how these molecular condensates can be directly probed.

PMID- 14683164
TI  - Bohr-Sommerfeld quantization condition for the Gross-Pitaevskii equation.
AB  - The discrete spectrum of the nonlinear eigenvalue problem associated to the one
      dimensional Gross-Pitaevskii equation with a smooth potential is studied in the
      quasiclassical limit. We particularly focus on the corrections to the Bohr
      Sommerfeld quantization rule for the excited energy levels due to the
      nonlinearity. Explicit predictions are obtained analytically for these
      corrections and are supported by numerical computations.

PMID- 14683165
TI  - Bell's theorem without inequalities and without alignments.
AB  - A proof of Bell's theorem without inequalities is presented which exhibits three
      remarkable properties: (a). reduced local states are immune to collective
      decoherence; (b). distant local setups do not need to be aligned, since the
      required perfect correlations are achieved for any local rotation of the local
      setups; (c). local measurements require only individual measurements on the
      qubits. Indeed, it is shown that this proof is essentially the only one which
      fulfills (a). (b). and (c).

PMID- 14683166
TI  - Quantum Zeno subspace and entangled Bose-Einstein condensates.
AB  - We discuss a proposal for the efficient generation of the maximally entangled
      atomic N-GHZ state in a spinor-1 condensate by driving internal state atomic
      Raman transitions using (classical) laser fields. We illustrate the dynamics in
      terms of a quantum Zeno subspace and identify the resultant atomic elastic
      collision in facilitating the deterministic entanglement creation. Our proposal
      can be readily implemented in several laboratories where ferromagnetic spinor
      condensates (of 87Rb atoms) are investigated.

PMID- 14683167
TI  - Entanglement of a mesoscopic field with an atom induced by photon graininess in a
      cavity.
AB  - We observe that a mesoscopic field made of several tens of microwave photons
      exhibits quantum features when interacting with a single Rydberg atom in a high-Q
      cavity. The field is split into two components whose phases differ by an angle
      inversely proportional to the square root of the average photon number. The field
      and the atomic dipole are phase entangled. These manifestations of photon
      graininess vanish at the classical limit. This experiment opens the way to
      studies of large quantum state superpositions at the quantum-classical boundary.

PMID- 14683168
TI  - Asymmetric Landau-Zener tunneling in a periodic potential.
AB  - Using a simple model for nonlinear Landau-Zener tunneling between two energy
      bands of a Bose-Einstein condensate in a periodic potential, we find that the
      tunneling rates for the two directions of tunneling are not the same. Tunneling
      from the ground state to the excited state is enhanced by the nonlinearity,
      whereas in the opposite direction it is suppressed. These findings are confirmed
      by numerical simulations of the condensate dynamics. Measuring the tunneling
      rates for a condensate of rubidium atoms in an optical lattice, we have found
      experimental evidence for this asymmetry.

PMID- 14683169
TI  - Stochastic resonance in a non-markovian discrete state model for excitable
      systems.
AB  - We study a non-Markovian three state model, subjected to an external periodic
      signal. This model is intended to describe an excitable system with periodical
      driving. In the limit of a small amplitude of the external signal we derive
      expressions for the spectral power amplification and the signal to noise ratio as
      well as for the interspike interval distribution.

PMID- 14683170
TI  - Relativistic chaos is coordinate invariant.
AB  - The noninvariance of Lyapunov exponents in general relativity has led to the
      conclusion that chaos depends on the choice of the space-time coordinates.
      Strikingly, we uncover the transformation laws of Lyapunov exponents under
      general space-time transformations and we find that chaos, as characterized by
      positive Lyapunov exponents, is coordinate invariant. As a result, the previous
      conclusion regarding the noninvariance of chaos in cosmology, a major claim about
      chaos in general relativity, necessarily involves the violation of hypotheses
      required for a proper definition of the Lyapunov exponents.

PMID- 14683171
TI  - New contribution to scattering of weakly interacting massive particles on nuclei.
AB  - A weakly interacting massive particle (WIMP) is perhaps the most promising
      candidate for the dark matter in the Galactic halo. The WIMP detection rate in
      laboratory searches is fixed by the cross section for elastic WIMP-nucleus
      scattering. Here we calculate the contribution to this cross section from two
      nucleon currents from pion exchange in the nucleus and show that it may, in some
      cases, be comparable to the one-nucleon current that has been considered in prior
      work and perhaps help resolve the discrepancies between the various direct dark
      matter search experiments. We provide simple expressions that allow these new
      contributions to be included in current calculations.

PMID- 14683172
TI  - Godel's universe in a Supertube shroud.
AB  - We demonstrate that certain supersymmetric Godel-like universe solutions of
      supergravity are not solutions of string theory. This is achieved by realizing
      that supertubes are Bogomol'nyi-Prasad-Sommerfeld states in these spaces, and
      under certain conditions, when wrapping closed timelike curves, some world-volume
      modes develop negative kinetic terms. Since these universes are homogeneous, this
      instability takes place everywhere in space-time. We also construct a family of
      supergravity solutions which locally look like the Godel universe inside a domain
      wall made out of supertubes, but have very different asymptotic structure. One
      can adjust the volume inside the domain wall so there will be no closed timelike
      curves, and then those spaces seem like perfectly good string backgrounds.

PMID- 14683173
TI  - Geometric scaling as traveling waves.
AB  - We show the relevance of the nonlinear Fisher and Kolmogorov-Petrovsky-Piscounov
      (KPP) equation to the problem of high energy evolution of the QCD amplitudes. We
      explain how the traveling wave solutions of this equation are related to
      geometric scaling, a phenomenon observed in deep-inelastic scattering
      experiments. Geometric scaling is for the first time shown to result from an
      exact solution of nonlinear QCD evolution equations. Using general results on the
      KPP equation, we compute the velocity of the wave front, which gives the full
      high energy dependence of the saturation scale.

PMID- 14683174
TI  - Understanding pentaquark States in QCD.
AB  - We estimate the mass of the pentaquark state with QCD sum rules and find that
      pentaquark states with isospin I=0,1,2 lie close to each other around (1.55+/
      0.15) GeV. The experimentally observed baryon resonance Theta(+)(1540) with S=+1
      can be consistently identified as a pentaquark state if its J(P)=1 / 2(-). Such a
      state is expected in QCD. If its parity is positive, this pentaquark state is
      really exotic. The outstanding issue now is to determine its quantum numbers
      experimentally.

PMID- 14683175
TI  - Diquarks and exotic spectroscopy.
AB  - We propose that the recently discovered Theta(+) baryon is a bound state of four
      quarks and an antiquark, containing two highly correlated ud pairs. If so, the
      theta(+) has positive parity, and it lies in an near-ideally mixed SU(3)(f)
      10;(f) plus sign in circle 8(f). The Roper resonance and the P11(1710) fit
      naturally into this classification. We predict an isospin 3/2 multiplet of Xi's
      (S=-2) with J(Pi)=1 / 2(+) around 1750 MeV. A search for manifestly exotic Xi(+)
      and Xi(--) in this mass range could provide a sharp test of our proposal. We
      predict that charm and bottom analogs of the Theta(+) may be stable against
      strong decays.

PMID- 14683176
TI  - Relation between proton and neutron asymptotic normalization coefficients for
      light mirror nuclei and its relevance to nuclear astrophysics.
AB  - We show how the charge symmetry of strong interactions can be used to relate the
      proton and neutron asymptotic normalization coefficients (ANCs) of the one
      nucleon overlap integrals for light mirror nuclei. This relation extends to the
      case of real proton decay where the mirror analog is a virtual neutron decay of a
      loosely bound state. In this case, a link is obtained between the proton width
      and the squared ANC of the mirror neutron state. The relation between mirror
      overlaps can be used to study astrophysically relevant proton capture reactions
      based on information obtained from transfer reactions with stable beams.

PMID- 14683177
TI  - Doorway states in the gamma decay-out of the yrast superdeformed band in 59Cu.
AB  - The decay-out process of the yrast superdeformed band in 59Cu has been
      investigated. The firm determination of spin, parity, excitation energy, and
      configuration of the states involved in this process constitutes a unique
      situation for a detailed understanding of the decay-out mechanism. A theoretical
      model is introduced that includes a residual interaction and tunneling matrix
      element between bands, calculated in the configuration-dependent cranked Nilsson
      Strutinsky model. This interaction causes the decay to occur via a small number
      of observed doorway states.

PMID- 14683178
TI  - Rovibrational-state-selected photoionization of acetylene by the two-color IR+VUV
      scheme: observation of rotationally resolved Rydberg transitions.
AB  - We have demonstrated a rovibrational-state-selected photoionization experiment
      using an IR laser and high-resolution VUV-synchrotron radiation. The VUV
      photoionization of acetylene [C2H2(Xtilde; (1)Sigma(+)(g);nu(3)=1,J(')=8 or 10)]
      prepared by IR excitation reveals three strong autoionizing Rydberg series
      converging to C2H+2(Xtilde; (2)Pi(u);nu(+)(3)=1) with little ion background
      interference. Rotational transitions resolved for the Rydberg states provide an
      estimate of approximately 1.8 ps for their lifetimes. This experiment opens the
      way for state-selective photoionization studies of polyatomic molecules using VUV
      synchrotron radiation.

PMID- 14683179
TI  - Trapping and manipulating neutral atoms with electrostatic fields.
AB  - We report on experiments with cold thermal (7)Li atoms confined in combined
      magnetic and electric potentials. A novel type of three-dimensional trap was
      formed by modulating a magnetic guide using electrostatic fields. We observed
      atoms trapped in a string of up to six individual such traps, a controlled
      transport of an atomic cloud over a distance of 400 microm, and a dynamic
      splitting of a single trap into a double well potential. Applications for quantum
      information processing are discussed.

PMID- 14683180
TI  - Resonant enhancement and dissipation in nonequilibrium van der Waals forces.
AB  - Dispersion forces between molecules that are in relative motion, coupled to baths
      at different temperatures, or in excited states, are calculated using a Green
      function Liouville space expansion that extends the celebrated McLachlan response
      theory to the nonlinear regime. Our dynamical theory is applicable to systems
      that may be in any initial nonequilibrium state and that are subject to an
      arbitrary time-dependent coupling. In contrast to equilibrium forces which are
      attractive, nonequilibrium forces may be attractive or repulsive, exhibit
      chemically specific resonances, are far stronger, and may be nonconservative
      (with either positive or negative dissipation).

PMID- 14683182
TI  - Xenon clusters in intense VUV laser fields.
AB  - A simple model is developed that quantitatively describes intense interactions of
      a vacuum ultraviolet (VUV) laser pulse with a xenon cluster. We find good
      agreement with a recent experiment [Nature (London) 420, 482 (2002)]]. In
      particular, the large number of VUV photons absorbed per atom, at intensities
      significantly below 10(16) W/cm(2), is now understood.

PMID- 14683181
TI  - Probing molecular dynamics at attosecond resolution with femtosecond laser
      pulses.
AB  - The kinetic energy distribution of D+ ions resulting from the interaction of a
      femtosecond laser pulse with D2 molecules is calculated based on the rescattering
      model. From analyzing the molecular dynamics, it is shown that the recollision
      time between the ionized electron and the D+2 ion can be read from the D+ kinetic
      energy peaks to attosecond accuracy. We further suggest that a more precise
      reading of the clock can be achieved by using shorter fs laser pulses (about 15
      fs).

PMID- 14683183
TI  - Phase control of collective quantum dynamics.
AB  - The manipulation of the steady-state behavior of a collection of dipole
      interacting three-level atoms in a V or Lambda configuration is investigated as a
      function of the relative phase of two strong coherent driving fields. For larger
      samples, the phase is shown to be a convenient parameter to rapidly populate or
      depopulate completely a trapping state of the ensemble. As applications, we
      present the appropriately prepared atomic sample as an optical switching device
      and show its virtues in controlling the collective steady-state resonance
      fluorescence intensity.

PMID- 14683184
TI  - Quasiperiodic Raman technique for ultrashort pulse generation.
AB  - We report the experimental demonstration of a new Raman technique that produces
      200 sidebands, ranging in wavelength from 3 microm to 195 nm. By studying
      multiphoton ionization of nitric oxide (NO) molecules, we show mutual phase
      coherence among 15 visible sidebands covering 0.63 octaves of bandwidth.

PMID- 14683185
TI  - Sharper focus for a radially polarized light beam.
AB  - We experimentally demonstrate for the first time that a radially polarized field
      can be focused to a spot size significantly smaller [0.16(1)lambda(2)] than for
      linear polarization (0.26lambda(2)). The effect of the vector properties of light
      is shown by a comparison of the focal intensity distribution for radially and
      azimuthally polarized input fields. For strong focusing, a radially polarized
      field leads to a longitudinal electric field component at the focus which is
      sharp and centered at the optical axis. The relative contribution of this
      component is enhanced by using an annular aperture.

PMID- 14683186
TI  - Propensity criterion for networking in an array of coupled chaotic systems.
AB  - We examine the mutual synchronization of a one-dimensional chain of chaotic
      identical objects in the presence of a stimulus applied to the first site. We
      first describe the characteristics of the local elements, and then the process
      whereby a global nontrivial behavior emerges. A propensity criterion for
      networking is introduced, consisting in the coexistence within the attractor of a
      localized chaotic region, which displays high sensitivity to external stimuli,
      and an island of stability, which provides a reliable coupling signal to the
      neighbors in the chain. Based on this criterion, we compare homoclinic chaos,
      recently explored in lasers and conjectured to be typical of a single neuron,
      with Lorenz chaos.

PMID- 14683187
TI  - Internal mode mechanism for collective energy transport in extended systems.
AB  - We study directed energy transport in homogeneous nonlinear extended systems in
      the presence of homogeneous ac forces and dissipation. We show that the mechanism
      responsible for unidirectional motion of topological excitations is the coupling
      of their internal and translation degrees of freedom. Our results lead to a
      selection rule for the existence of such motion based on resonances that explain
      earlier symmetry analysis of this phenomenon. The direction of motion is found to
      depend both on the initial and the relative phases of the two harmonic drivings,
      even in the presence of noise.

PMID- 14683188
TI  - Secondary instabilities and vortex formation in collisionless-fluid magnetic
      reconnection.
AB  - It is shown that the pattern of current layers formed within a magnetic island in
      the nonlinear phase of magnetic field line reconnection in a collisionless two
      dimensional fluid plasma is subject to the onset of a secondary instability, the
      effect of which increases with decreasing electron temperature. In the cold
      electron limit the saturation of the island growth is accompanied by a turbulent
      redistribution of the current layers and by the development of long lived fluid
      vortices while, in the opposite limit, the current layer structure remains
      regular.

PMID- 14683189
TI  - Preheat effects on shock propagation in indirect-drive inertial confinement
      fusion ablator materials.
AB  - The velocities and temperatures of shock waves generated by laser-driven hohlraum
      radiation fields have been measured for several indirect-drive inertial
      confinement fusion capsule ablator materials. For the first time, a time-resolved
      measurement of the preheat temperature ahead of the shock front has been
      performed and included in the analysis. It is found that preheat ahead of the
      shock front can cause significant shock propagation variations in the ignition
      capsule ablator materials being considered for the National Ignition Facility
      (NIF). If unaccounted for, these preheat effects could potentially preclude
      ignition at the NIF.

PMID- 14683190
TI  - Substrate-tuned boson localization in superfluid (4)He films.
AB  - We have studied the influence of the substrate on superfluidity in thin 4He
      films. The inert coverage, the amount of nonsuperfluid 4He localized by the
      substrate, is found to scale with the well depth of the 4He-substrate interaction
      potential for six different substrates. Although the inert coverages for these
      substrates differ by more than a factor of 4, the phase boundary in the
      temperature-coverage plane is found to have a universal shape.

PMID- 14683191
TI  - Interactions between sheets of phonons in liquid (4)He.
AB  - We have created two sheets of approximately 1 K phonons in liquid (4)He at
      approximately 55 mK such that they intersect each other as they move towards a
      common point. If the two sheets have a small angle between them, they interact
      strongly and create a hot line in the liquid helium. This line is continuously
      fed with energy from the two sheets and loses energy by creating high-energy
      phonons. If the angle between the sheets is larger than approximately 30 degrees
      they do not interact but pass through each other. These results give direct
      evidence for the composition of the sheets: they comprise strongly interacting
      low-energy phonons which occupy a narrow cone in momentum space.

PMID- 14683192
TI  - What does the potential energy landscape tell us about the dynamics of
      supercooled liquids and glasses?
AB  - For a model glass former we demonstrate via computer simulations how macroscopic
      dynamic quantities can be inferred from a potential energy landscape (PEL)
      analysis. The essential step is to consider whole superstructures of many PEL
      minima, called metabasins, rather than single minima. We show that two types of
      metabasins exist: some allowing for quasifree motion on the PEL (liquidlike), and
      the others acting as traps (solidlike). The activated, multistep escapes from the
      latter metabasins are found to dictate the slowing down of dynamics upon cooling
      over a much broader temperature range than is currently assumed.

PMID- 14683193
TI  - Interaction of shear waves and propagating cracks.
AB  - Shear waves generated from an ultrasonic transducer are used to twist dynamically
      growing crack fronts; the response of crack front to such external perturbations
      is examined in order to investigate the primary cause of surface roughening in
      brittle materials. The response of the crack front is found to be linear in
      amplitude and frequency of the perturbing wave and without persistence. The
      response to random perturbations, e.g., by localized material inhomogeneities at
      the free surface, is also discussed.

PMID- 14683194
TI  - Charge state dependent Jahn-Teller distortions of the e-center defect in
      crystalline Si.
AB  - The atomic and electronic structures of a lattice vacancy trapped next to an As
      impurity (the E-center defect) in crystalline Si are investigated using ab initio
      pseudopotential total energy calculations. Jahn-Teller distortions and energies,
      reorientation barriers, defect wave function characters, and hyperfine coupling
      parameters associated with (-) and (0) charge states of the E center are
      calculated using a combination of real-space cluster and plane wave supercell
      methods. For the first time in the theoretical study of this defect, the senses
      of the Jahn-Teller distortions in the two charge states are found to be opposite,
      changing from a large pairing type in (0) to a large resonant-bond type
      distortion in the (-) charge state, in agreement with experimental data.

PMID- 14683195
TI  - Microscopic origin of the nonexponential dynamics in a glassy crystal.
AB  - The origin of the slow relaxation and of the dynamic heterogeneity is studied for
      an orientation-ally disordered crystal, orthocarborane, composed of quasi
      icosahedrally shaped molecules. Multidimensional deuteron magnetic resonance
      reveals that large jump angles dominate their complex, anisotropic
      reorientational motion. It involves a sequence of small-angle tilts about locally
      preferred axes as well as symmetry adapted threefold jumps. The intrinsic
      dynamics of this glassy crystal is nonexponential and can be fully accounted for
      in terms of the tilt and jump motion.

PMID- 14683196
TI  - Driven alloys in the athermal limit.
AB  - Static molecular simulations of binary alloys under extrinsic forcing show that
      complex ordered or segregated structures may evolve even in the absence of
      thermally activated diffusion. This result is in opposition to the standard
      theoretical framework for so-called "driven alloys," which assumes that extrinsic
      driving is an ideally randomizing process, and therefore predicts only random
      atomic configurations in the athermal limit. We propose a qualitative
      modification to the theory that introduces a new control parameter and use
      additional Monte Carlo simulations to demonstrate the physical plausibility of
      this modification. New research directions in nonequilibrium dynamic systems are
      also suggested by this analysis.

PMID- 14683197
TI  - Force-extension curve of a polymer in a high-frequency electric field.
AB  - We study theoretically the conformation and force-extension curve of a
      semiflexible polymer in a spatially uniform ac electric field. The polymer
      backbone minimizes its energy by aligning along one of two orientations parallel
      to the field. In a strong ac field, hairpin kinks develop between regions of
      opposite alignment. These kinks are mathematically described as sine-Gordon
      solitons. We calculate the equation of state of the one-dimensional kink gas,
      which yields the force-extension curve of the polymer. A sufficiently strong ac
      field causes the polymer to extend spontaneously to almost its full contour
      length. The theory is applied to recent experiments on dielectrophoretic
      stretching of DNA.

PMID- 14683198
TI  - Defect structure around two colloids in a liquid crystal.
AB  - This Letter investigates the defect structures that arise between two colloidal
      spheres immersed in a nematic liquid crystal. Molecular simulations and a dynamic
      field theory are employed to arrive at molecular-level and mesoscopic
      descriptions of the systems of interest. At large separations, each sphere is
      surrounded by a Saturn ring defect. However, at short separations both theory and
      simulation predict that a third disclination ring appears in between the spheres,
      in a plane normal to the Saturn rings. This feature gives rise to an effective
      binding of the particles. The structures predicted by field theory and molecular
      simulations are consistent with each other.

PMID- 14683199
TI  - Free surfaces cause reductions in the glass transition temperature of thin
      polystyrene films.
AB  - The effect of free surfaces on the glass transition temperature (T(g)) of thin
      polystyrene films was studied. Measurements were performed on films (8 nm<h<290
      nm) with one free surface and on films capped with a 5 nm thick metal layer (no
      free surfaces). Potential problems with evaporative deposition were eliminated by
      studying samples made of two supported films placed with their free surfaces in
      contact and annealed. Uncapped films displayed reduced T(g) values for h less,
      similar 40 nm while all "properly" capped films exhibited a T(g) value the same
      as that of the bulk polymer (370+/-1 K). When the free surface was restored, the
      measured T(g) values the same as those of uncapped films of the same thickness.
      These results show that free surfaces are crucial for observing T(g) reductions
      in thin polymer films and address the role of the sample preparation history.

PMID- 14683200
TI  - Theory of transport of long polymer molecules through carbon nanotube channels.
AB  - A theory of transport of long chain polymer molecules through carbon nanotube
      (CNT) channels is developed using the Fokker-Planck equation and direct molecular
      dynamics simulations. The mean transport or translocation time tau is found to
      depend on the chemical potential energy, the entropy, and the diffusion
      coefficient. A power law dependence tau approximately N2 is found, where N is the
      number of monomers in a molecule. For 10(5)-unit long polyethylene molecules, tau
      is estimated to be approximately 1 micros. The diffusion coefficient of long
      polymer molecules inside CNTs, like that of short ones, is found to be a few
      orders of magnitude larger than in ordinary silicate based zeolite systems.

PMID- 14683201
TI  - Kinetic wetting of a moving planar defect by a new phase.
AB  - Close to a bulk phase transition, a moving planar defect can be covered by a
      layer of the ordered phase. This, in fact, happens above the transition point in
      some finite region of the temperature-velocity diagram. In the case of a first
      order transition this region is furnished with a net of nonequilibrium phase
      transition lines. The topology of this net resembles that of the phase diagram of
      a first-order wetting transition in thermal equilibrium. In particular, there
      appears a kinetic complete-wetting line where a significant change of the drag
      coefficient of the defect is predicted.

PMID- 14683202
TI  - Precursor film controlled wetting of Pb on Cu.
AB  - Wetting in a system where the kinetics of drop spreading are controlled by the
      rate of formation of a precursor film is modeled for the first time at the
      atomistic scale. Molecular dynamics simulations of Pb(l) wetting Cu(111) and
      Cu(100) show that a precursor film of atomic thickness evolves and spreads
      diffusively. This precursor film spreads significantly faster on Cu(111) than on
      Cu(100). For Cu(100), the kinetics of drop spreading are dramatically decreased
      by slow advancement of the precursor film. Slow precursor film kinetics on
      Cu(100) are partly due to the formation of a surface alloy at the solid-liquid
      interface which does not occur on Cu(111).

PMID- 14683204
TI  - Electron field emission properties of closed carbon nanotubes.
AB  - Recent experiments have shown that carbon nanotubes exhibit excellent electron
      field emisson properties with high current densities at low electric fields. Here
      we present theoretical investigations that incorporate geometrical effects and
      the electronic structure of nanotubes. The electric field is dramatically
      enhanced near the cap of a nanotube with a large variation of local field
      distribution. It is found that deviation from linear Fowler-Nordheim behavior
      occurs due to the variation of the local field in the electron tunneling region.
      The maximum current per tube is of the order of 10 microA. Local and microscopic
      aspects of field emission from nanotubes are also presented.

PMID- 14683203
TI  - Optical conductivity of the Frohlich polaron.
AB  - We present accurate results for optical conductivity of the three dimensional
      Frohlich polaron in all coupling regimes. The systematic-error free diagrammatic
      quantum Monte Carlo method is employed where the Feynman graphs for the momentum
      momentum correlation function in imaginary time are summed up. The real-frequency
      optical conductivity is obtained by the analytic continuation with stochastic
      optimization. We compare numerical data with available perturbative and
      nonperturbative approaches to the optical conductivity and show that the picture
      of sharp resonances due to relaxed excited states in the strong-coupling regime
      is "washed out" by large broadening of these states. As a result, the spectrum
      contains only a single-maximum broad peak with peculiar shape and a shoulder.

PMID- 14683205
TI  - Near-perfect correlation of the resistance components of mesoscopic samples at
      the quantum Hall regime.
AB  - We study the four-terminal resistance fluctuations of mesoscopic samples near the
      transition between the nu=2 and the nu=1 quantum Hall states. We observe near
      perfect correlations between the fluctuations of the longitudinal and Hall
      components of the resistance. These correlated fluctuations appear in a magnetic
      field range for which the two-terminal resistance of the samples is quantized. We
      discuss these findings in light of edge-state transport models of the quantum
      Hall effect. We also show that our results lead to an ambiguity in the
      determination of the width of quantum Hall transitions.

PMID- 14683206
TI  - Eight-dimensional quantum Hall effect and "Octonions".
AB  - We construct a generalization of the quantum Hall effect where particles move in
      an eight-dimensional space under an SO(8) gauge field. The underlying mathematics
      of this particle liquid is that of the last normed division algebra, the
      octonions. Two fundamentally different liquids with distinct configuration spaces
      can be constructed, depending on whether the particles carry spinor or vector
      SO(8) quantum numbers. One of the liquids lives on a 20-dimensional manifold with
      an internal component of SO(7) holonomy, whereas the second liquid lives on a 14
      dimensional manifold with an internal component of G2 holonomy.

PMID- 14683207
TI  - Quantum criticality of D-wave quasiparticles and superconducting phase
      fluctuations.
AB  - We present finite temperature (T) extension of the (2+1)-dimensional QED (QED3)
      theory of under-doped cuprates. The theory describes nodal quasiparticles whose
      interactions with quantum proliferated hc/2e vortex-antivortex pairs are
      represented by an emergent U(1) gauge field. Finite T introduces a scale beyond
      which the spatial fluctuations of vorticity are suppressed. As a result, the spin
      susceptibility of the pseudogap state is bounded by T2 at low T and crosses over
      to approximately T at higher T, while the low-T specific heat scales as T2,
      reflecting the thermodynamics of QED3. The Wilson ratio vanishes as T-->0; the
      pseudogap state is a "thermal (semi)metal" but a "spin-charge dielectric." This
      non-Fermi liquid behavior originates from two general principles: spin
      correlations induced by "gauge" interactions of quasiparticles and fluctuating
      vortices and the "relativistic" scaling of the T=0 fixed point.

PMID- 14683208
TI  - Two resonant magnetic modes in an overdoped high T(c) superconductor.
AB  - A detailed inelastic neutron scattering study of the overdoped high temperature
      copper oxide superconductor Y(0.9)Ca(0.1)Ba(2)Cu(3)O(7) reveals two-distinct
      magnetic resonant modes in the superconducting state. The modes differ in their
      symmetry with respect to exchange between adjacent copper oxide layers.
      Counterparts of the mode with odd symmetry, but not the one with even symmetry,
      had been observed before at lower doping levels. The observation of the even mode
      resolves a long-standing puzzle, and the spectral weight ratio of both modes
      yields an estimate of the onset of particle-hole spin-flip excitations.

PMID- 14683209
TI  - Hysteretic spin-density-wave ordering in confined geometries.
AB  - We have measured the antiferromagnetic spin-density-wave (SDW) order in
      Cr/Cr(97.5)Mn2.5(001) superlattices. The Mn doping creates a high Neel
      temperature layer that confines the incommensurate SDW order within the Cr
      layers. With temperature cycling we observe a transition from commensurate to
      incommensurate SDW order and discrete changes in the SDW period. We find that
      these transitions show significant hysteresis (up to 75 K) when the number of SDW
      nodes within the Cr layer changes by an odd number, while there is no hysteresis
      for changes of an even number of nodes. This results from the competition between
      maintaining the spin structure at the interfaces and introducing a spin slip at
      the nodes of the Cr SDW.

PMID- 14683210
TI  - Elementary excitations in the cyclic molecular nanomagnet Cr8.
AB  - Combining recent and new inelastic neutron scattering data for the molecular
      cyclic cluster Cr8 produces a deep understanding of the low lying excitations in
      bipartite antiferromagnetic Heisenberg rings. The existence of the L band, the
      lowest rotational band, and the E band, essentially spin wave excitations, is
      confirmed spectroscopically. The different significance of these excitations and
      their physical nature is clearly established by high-energy and Q-dependence
      data.

PMID- 14683211
TI  - Ferromagnetism in fcc twinned 2.4 nm size Pd nanoparticles.
AB  - The onset of ferromagnetism has been experimentally observed in small Pd
      particles of average diameter 2.4 nm. High-resolution studies reveal that a high
      percentage of the fcc particle exhibits single and multiple twinning boundaries.
      The spontaneous magnetization close to 0.02 emu/g seems to indicate that only a
      small fraction of atoms holds a permanent magnetic moment and contributes to
      ferromagnetism. The possible origin of ferromagnetism is briefly discussed
      according to different models recently reported.

PMID- 14683212
TI  - Magnetism in all-carbon nanostructures with negative Gaussian curvature.
AB  - We apply the ab initio spin density functional theory to study magnetism in all
      carbon nanostructures. We find that particular systems, which are related to
      schwarzite and contain no undercoordinated carbon atoms, carry a net magnetic
      moment in the ground state. We postulate that, in this and other nonalternant
      aromatic systems with negative Gaussian curvature, unpaired spins can be
      introduced by sterically protected carbon radicals.

PMID- 14683213
TI  - Magnetostrictive domain walls in antiferromagnetic NiO.
AB  - We report high-resolution observations of antiferromagnetic (AF) domain walls at
      the surface of NiO and determine the typical width of AF walls in this material
      to be of the order of 150 nm. We observe a number of different types of domain
      walls, including double walls caused by long-range interaction between walls. We
      describe the observed wall profiles by a model containing the exchange
      interaction and magnetostriction as basic ingredients. The good agreement of this
      model with experiment shows that the formation of walls between antiferromagnetic
      domains in NiO and their properties are dominated by magnetoelastic interactions.

PMID- 14683214
TI  - Interband impact ionization and nonlinear absorption of terahertz radiation in
      semiconductor heterostructures.
AB  - We have theoretically investigated nonlinear free-carrier absorption of terahertz
      (THz) radiation in InAs/AlSb heterojunctions. By considering multiple photon
      process and conduction-valence interband impact ionization (II), we have
      determined the field and frequency dependent absorption rate. It is shown that
      (i). electron-disorder scatterings are important at low to intermediate field,
      and (ii). most importantly, the high field absorption is dominated by II
      processes. Our theory can satisfactorily explain a long-standing experimental
      result on the nonlinear absorption in the THz regime.

PMID- 14683215
TI  - Hydrogen bond dynamics probed with ultrafast infrared heterodyne-detected
      multidimensional vibrational stimulated echoes.
AB  - Hydrogen bond dynamics are explicated with exceptional detail using
      multidimensional infrared vibrational echo correlation spectroscopy with full
      phase information. Probing the hydroxyl stretch of methanol-OD oligomers in CCl4,
      the dynamics of the evolving hydrogen bonded network are measured with ultrashort
      (<50 fs) pulses. The data along with detailed model calculations demonstrate that
      vibrational relaxation leads to selective hydrogen bond breaking on the red side
      of the spectrum (strongest hydrogen bonds) and the production of singly hydrogen
      bonded photoproducts.

PMID- 14683216
TI  - Quantum logic approach to wave packet control.
AB  - We study control of wave packets with a finite accuracy, approaching it as
      quantum information processing. For a given control resolution, we define the
      analogs of several quantum bits within the shape of a single wave packet. These
      bits are based on wave packet symmetries. Analogs of one- and two-bit gates can
      be implemented using only free wave packet evolution and coordinate-dependent ac
      Stark shifts applied at the moments of fractional revivals. As in quantum
      computation, the gates form a logarithmically small set of basis operations which
      can be used to approximate any unitary transformation desired for quantum control
      of the wave packet dynamics. Numerical examples show the application of this
      approach to control vibrational wave packet revivals.

PMID- 14683217
TI  - Noise-controlled self-replicating patterns.
AB  - We present novel numerical evidence of spot self-replication controlled by noise
      in a simple autocatalytic reaction-diffusion system. The system dynamics exhibits
      a noise controlled transition from stripe growth to spot replication. The growth
      kinetics is also controlled by noise, and there is an optimal noise intensity for
      which the multiplication rate of spots is maximal. For larger noise intensities,
      the spots become unstable and the system is attracted by the trivial steady
      state. Some of the effects are reminiscent of both polymer chain and cell colony
      formation in random environments.

PMID- 14683218
TI  - Hysteresis in one-dimensional reaction-diffusion systems.
AB  - We introduce a simple nonequilibrium model for a driven diffusive system with
      nonconservative reaction kinetics in one dimension. The steady state exhibits a
      phase with broken ergodicity and hysteresis which has no analog in systems
      investigated previously. We identify the main dynamical mode, viz., the random
      motion of a shock in an effective potential, which provides a unified framework
      for understanding phase coexistence as well as ergodicity breaking. This picture
      also leads to the exact phase diagram of the system.

PMID- 14683219
TI  - Ergodic dynamics in a natural threshold system.
AB  - Numerical simulations suggest that certain driven, dissipative mean-field
      threshold systems, including earthquake models, can be characterized by
      statistical properties often associated with ergodic dynamics, in the same sense
      as stochastic Brownian motion. We applied a fluctuation metric proposed by
      Thirumalai and Mountain [Phys. Rev. E 47, 479 (1993)]] for statistically
      stationary systems and find that the natural earthquake fault system in
      California demonstrates similar ergodic dynamics.

PMID- 14683221
TI  - Comment on "probable Langevin-like director reorientation in an interface-induced
      disordered SmC(*)-like state of liquid crystals characterized by frustration
      between ferro- and antiferroelectricity".

PMID- 14683220
TI  - Network information and connected correlations.
AB  - Entropy and information provide natural measures of correlation among elements in
      a network. We construct here the information theoretic analog of connected
      correlation functions: irreducible N-point correlation is measured by a decrease
      in entropy for the joint distribution of N variables relative to the maximum
      entropy allowed by all the observed N-1 variable distributions. We calculate the
      "connected information" terms for several examples and show that it also enables
      the decomposition of the information that is carried by a population of elements
      about an outside source.

PMID- 14683223
TI  - Minimal Brownian ratchet: an exactly solvable model.
AB  - We develop an analytically solvable three-state discrete-time minimal Brownian
      ratchet (MBR), where the transition probabilities between states are asymmetric.
      By solving the master equations, we obtain the steady-state probabilities.
      Generally, the steady-state solution does not display detailed balance, giving
      rise to an induced directional motion in the MBR. For a reduced two-dimensional
      parameter space, we find the null curve on which the net current vanishes and
      detailed balance holds. A system on this curve is said to be balanced. On the
      null curve, an additional source of external random noise is introduced to show
      that a directional motion can be induced under the zero overall driving force.

PMID- 14683224
TI  - Experimental evidence of "vibrational resonance" in an optical system.
AB  - The experimental evidence and characterization of "vibrational resonance" in a
      bistable vertical cavity laser are reported. The system is driven by two periodic
      forcings, with frequencies differing by several orders and studied in the case of
      both symmetrical and asymmetrical quasipotentials. The phenomenon shows up in the
      dynamics of the polarized laser emission as a resonance in the low-frequency
      response and signal-to-noise ratio, depending on the amplitude of an applied high
      frequency modulation. The possibility to use the phenomenon for low-level
      detection is experimentally demonstrated.

PMID- 14683225
TI  - Universal thermal radiation drag on neutral objects.
AB  - We compute the force on a small neutral polarizable object moving at velocity v-
      > relative to a photon gas equilibrated at a temperature T. We find a drag force
      linear in v-->. Its physical basis is related to that in recent formulations of
      the dissipative component of the Casimir force, i.e., the change in photon
      momentum in emission and absorption between the moving body and the stationary
      thermal bath. We estimate the strength of this universal drag force for different
      dielectric response functions and comment on its relevance in various contexts,
      especially to radiation-matter coupling in the cosmos.

PMID- 14683226
TI  - Cosmic microwave background radiation anisotropies in brane worlds.
AB  - We propose a new formulation to calculate the cosmic microwave background (CMB)
      spectrum in the Randall-Sundrum two-brane model based on recent progress in
      solving the bulk geometry using a low energy approximation. The evolution of the
      anisotropic stress imprinted on the brane by the 5D Weyl tensor is calculated. An
      impact of the dark radiation perturbation on the CMB spectrum is investigated in
      a simple model assuming an initially scale-invariant adiabatic perturbation. The
      dark radiation perturbation induces isocurvature perturbations, but the resultant
      spectrum can be quite different from the prediction of simple mixtures of
      adiabatic and isocurvature perturbations due to Weyl anisotropic stress.

PMID- 14683227
TI  - Can cosmic shear shed light on low cosmic microwave background multipoles?
AB  - The lowest multipole moments of the cosmic microwave background (CMB) are smaller
      than expected for a scale-invariant power spectrum. One possible explanation is a
      cutoff in the primordial power spectrum below a comoving scale of k(c)
      approximately equal to 5.0 x 10(-4) Mpc(-1). Such a cutoff would increase
      significantly the cross correlation between the large-angle CMB and cosmic-shear
      patterns. The cross correlation may be detectable at >2sigma which, combined with
      the low CMB moments, may tilt the balance between a 2sigma result and a firm
      detection of a large-scale power-spectrum cutoff. The cutoff also increases the
      large-angle cross correlation between the CMB and the low-redshift tracers of the
      mass distribution.

PMID- 14683230
TI  - Functional integrals for QCD at nonzero chemical potential and zero density.
AB  - In a Euclidean space functional integral treatment of the free energy of QCD, a
      chemical potential enters only through the functional determinant of the Dirac
      operator which for any flavor is /D+m-mu(f)gamma(0) (where mu(f) is the chemical
      potential for the given flavor). Any nonzero mu alters all of the eigenvalues of
      the Dirac operator relative to the mu=0 value, leading to a naive expectation
      that the determinant is altered and which thereby alters the free energy.
      Phenomenologically, this does not occur at T=0 for sufficiently small mu, in
      contradiction to this naive expectation. The problem of how to understand this
      phenomenological behavior in terms of functional integrals is solved for the case
      of an isospin chemical through the study of the spectrum of the operator
      gamma(0)(/D+m). The case of the baryon chemical potential is briefly discussed.

PMID- 14683232
TI  - Differential cross sections for Higgs boson production at tevatron collider
      energies.
AB  - The transverse momentum Q(T) distribution is computed for inclusive Higgs boson
      production at sqrt[S]=1.96 TeV. We include all-orders resummation of large
      logarithms associated with emission of soft gluons at small Q(T). We provide
      results for Higgs boson and Z* masses from M(Z) to 200 GeV. The relatively hard
      transverse momentum distribution for Higgs boson production suggests
      possibilities for improvement of the signal to background ratio.

PMID- 14683233
TI  - Spectroscopy of the 1S0-3P0 clock transition of 87Sr in an optical lattice.
AB  - We report on the spectroscopy of the 5s(2) 1S0(F=9/2)-->5s5p 3P0(F=9/2) clock
      transition of 87Sr atoms (natural linewidth of 1 mHz) trapped in a one
      dimensional optical lattice. Recoilless transitions with a linewidth of 0.7 kHz
      as well as the vibrational structure of the lattice potential were observed. By
      investigating the wavelength dependence of the carrier linewidth, we determined
      the magic wavelength, where the light shift in the clock transition vanishes, to
      be 813.5+/-0.9 nm.

PMID- 14683228
TI  - Observation of B-/+-->rho-/+rho0 decays.
AB  - We report the first observation of the charmless vector-vector decay process B-/+
      ->rho(-/+)rho(0). The measurement uses a 78 fb(-1) data sample collected with the
      Belle detector at the KEKB asymmetric e(+)e(-) collider operating at the
      Upsilon(4S) resonance. We obtain a branching fraction of B(B-/+-->rho(
      /+)rho(0))=[31.7+/-7.1(stat)+3.8-6.7(syst)]x10(-6). An analysis of the rho
      helicity-angle distributions gives a longitudinal polarization fraction of
      Gamma(L)/Gamma=0.95+/-0.11(stat)+/-0.02(syst). We also measure the direct-CP
      violating asymmetry A(CP)(B-/+-->rho(-/+)rho(0))=0.00+/-0.22(stat)+/-0.03(syst).

PMID- 14683234
TI  - Direct measurement of the thermal rate coefficient for electron attachment to
      ozone in the gas phase, 300-550 K: implications for the ionosphere.
AB  - Attachment of thermal electrons to O3 was studied in 133 Pa He between 300-550 K;
      the process is extremely inefficient. The rate coefficient increases sharply with
      temperature from 0.9 to 5 x 10(-11) cm(3) s(-1) (+/-30%) and comparison to
      kinetic energy measurements suggests internal energy can drive the reaction.
      These determinations account for competing processes of diffusion, recombination,
      and electron detachment reactions, and imply that no significant zero-energy
      resonance cross section exists, contradicting recent electron-beam results that
      call for substantial revision of ionospheric models.

PMID- 14683235
TI  - Ionization of Clusters in Intense Laser Pulses through Collective Electron
      Dynamics.
AB  - The motion of electrons and ions in medium-sized rare gas clusters (
      approximately 1000 atoms) exposed to intense laser pulses is studied
      microscopically by means of classical molecular dynamics using a hierarchical
      tree code. Pulse parameters for optimum ionization are found to be wavelength
      dependent. This resonant behavior is traced back to a collective electron
      oscillation inside the charged cluster. It is shown that this dynamics can be
      well described by a driven and damped harmonic oscillator allowing for a clear
      discrimination against other energy absorption mechanisms.

PMID- 14683236
TI  - Nonlinear bound-free pair creation in the strong electromagnetic fields of a
      heavy nucleus and an intense x-ray laser.
AB  - We study e(-)e(+) pair creation in the collision of a heavy nucleus with an
      intense x-ray laser, where the produced e(-) is simultaneously captured into the
      K shell of the projectile nucleus. The parameters of the colliding system are
      chosen such that the absorption of at least two photons from the laser wave is
      required in order to surmount the energy threshold of the reaction. Considering
      this fundamental nonlinear strong-field process for the first time, we estimate
      the total production rate as well as the angular and energetic distributions of
      the emitted positrons. According to our results, the process of nonlinear bound
      free pair creation could become observable by the aid of the upcoming x-ray laser
      facilities.

PMID- 14683231
TI  - Measurement of the proton spin structure function g1(x,Q2) for Q2 from 0.15 to
      1.6 GeV2 with CLAS.
AB  - Double-polarization asymmetries for inclusive ep scattering were measured at
      Jefferson Lab using 2.6 and 4.3 GeV longitudinally polarized electrons incident
      on a longitudinally polarized NH3 target in the CLAS detector. The polarized
      structure function g(1)(x,Q2) was extracted throughout the nucleon resonance
      region and into the deep inelastic regime, for Q(2)=0.15-1.64 GeV2. The
      contributions to the first moment Gamma(1)(Q2)= integral g(1)(x,Q2) dx were
      determined up to Q(2)=1.2 GeV2. Using a parametrization for g(1) in the
      unmeasured low x regions, the complete first moment was estimated over this Q2
      region. A rapid change in Gamma(1) is observed for Q2<1 GeV2, with a sign change
      near Q(2)=0.3 GeV2, indicating dominant contributions from the resonance region.
      At Q(2)=1.2 GeV2 our data are below the perturbative QCD evolved scaling value.

PMID- 14683237
TI  - Strong spatiotemporal localization in a silica nonlinear waveguide array.
AB  - We investigate the propagation of short, intense laser pulses in arrays of
      coupled silica waveguides, in the anomalous dispersion regime. The nonlinearity
      induces trapping of the pulse in a single waveguide, over a wide range of input
      parameters. A sharp transition is observed for single waveguide excitation, from
      strong diffraction at low powers to strong localization at high powers.

PMID- 14683238
TI  - Attosecond angle-resolved photoelectron spectroscopy.
AB  - We report experiments on the characterization of a train of attosecond pulses
      obtained by high-harmonic generation, using mixed-color (XUV+IR) atomic two
      photon ionization and electron detection on a velocity map imaging detector. We
      demonstrate that the relative phase of the harmonics is encoded both in the
      photoelectron yield and the angular distribution as a function of XUV-IR time
      delay, thus making the technique suitable for the detection of single attosecond
      pulses. The timing of the attosecond pulse with respect to the field oscillation
      of the driving laser critically depends on the target gas used to generate the
      harmonics.

PMID- 14683239
TI  - Supermodes of chiral photonic filters with combined twist and layer defects.
AB  - We consider the circularly polarized localized modes of chiral photonic
      structures with combined central twist and isotropic layer defects. The general
      filter is shown to suffer from anomalous remittance and saturation of linewidth
      as the thickness of the structure is increased. However, by choosing parameters
      that phase match the elements of the round-trip matrix of the isotropic layer
      defect, we demonstrate the existence of supermodes that maintain exceptional
      purity of polarization state and exponential decrease in linewidth as the
      thickness is increased.

PMID- 14683240
TI  - Slow diffusion of light in a cold atomic cloud.
AB  - We study the diffusive propagation of multiply scattered light in an optically
      thick cloud of cold rubidium atoms illuminated by a quasiresonant laser beam. In
      the vicinity of a sharp atomic resonance, the energy transport velocity of the
      scattered light is almost 5 orders of magnitude smaller than the vacuum speed of
      light, reducing strongly the diffusion constant. We verify the theoretical
      prediction of a frequency-independent transport time around the resonance. We
      also observe the effect of the residual velocity of the atoms at long times.

PMID- 14683241
TI  - Superpersistent chaotic transients in physical space: advective dynamics of
      inertial particles in open chaotic flows under noise.
AB  - Superpersistent chaotic transients are characterized by an exponential-like
      scaling law for their lifetimes where the exponent in the exponential dependence
      diverges as a parameter approaches a critical value. So far this type of
      transient chaos has been illustrated exclusively in the phase space of dynamical
      systems. Here we report the phenomenon of noise-induced superpersistent
      transients in physical space and explain the associated scaling law based on the
      solutions to a class of stochastic differential equations. The context of our
      study is advective dynamics of inertial particles in open chaotic flows. Our
      finding makes direct experimental observation of superpersistent chaotic
      transients feasible. It also has implications to problems of current concern such
      as the transport and trapping of chemically or biologically active particles in
      large-scale flows.

PMID- 14683242
TI  - Flow and fracture in drying nanoparticle suspensions.
AB  - Drying aqueous suspensions of monodisperse silica nanoparticles can fracture in
      remarkable patterns. As the material solidifies, evenly spaced cracks invade from
      the drying surface, with individual cracks undergoing intermittent motion. We
      show that the growth of cracks is limited by the advancement of the compaction
      front, which is governed by a balance of evaporation and flow of fluid at the
      drying surface. Surprisingly, the macroscopic dynamics of drying show signatures
      of molecular-scale fluid effects.

PMID- 14683243
TI  - Traveling waves in pipe flow.
AB  - A family of three-dimensional traveling waves for flow through a pipe of circular
      cross section is identified. The traveling waves are dominated by pairs of
      downstream vortices and streaks. They originate in saddle-node bifurcations at
      Reynolds numbers as low as 1250. All states are immediately unstable. Their
      dynamical significance is that they provide a skeleton for the formation of a
      chaotic saddle that can explain the intermittent transition to turbulence and the
      sensitive dependence on initial conditions in this shear flow.

PMID- 14683244
TI  - Vortex-pair dynamics in anisotropic bistable media: a kinematic approach.
AB  - In isotropic bistable media, a vortex pair typically evolves into rotating spiral
      waves. In an anisotropic system, instead of spiral waves, the vortices can form
      wave fragments that propagate with a constant speed in a given direction
      determined by the system's anisotropy. The fragments may propagate invariably,
      shrink, or expand. We develop a kinematic approach for the study of vortex-pair
      dynamics in anisotropic bistable media and use it to capture the wave fragment
      dynamics.

PMID- 14683245
TI  - Laser-energy transfer and enhancement of plasma waves and electron beams by
      interfering high-intensity laser pulses.
AB  - The effects of interference due to crossed laser beams were studied
      experimentally in the high-intensity regime. Two ultrashort (400 fs), high
      intensity (4 x 10(17) and 1.6 x 10(18) W/cm(2)) and 1 microm wavelength laser
      pulses were crossed in a plasma of density 4 x 10(19) cm(3). Energy was observed
      to be transferred from the higher-power to the lower-power pulse, increasing the
      amplitude of the plasma wave propagating in the direction of the latter. This
      results in increased electron self-trapping and plasma-wave acceleration
      gradient, which led to an increased number of hot electrons (by 300%) and hot
      electron temperature (by 70%) and a decreased electron-beam divergence angle (by
      45%), as compared with single-pulse illumination. Simulations reveal that
      increased stochastic heating of electrons may have also contributed to the
      electron-beam enhancement.

PMID- 14683246
TI  - Critical velocity of continuous vortex nucleation in a slab of superfluid 3He-A.
AB  - A flow-induced Freedericksz transition is observed in a 0.26 mm thick disk-shaped
      slab of superfluid 3He-A using a rotating cryostat and a torsional oscillator,
      and it is used to detect vortices in zero magnetic field. The phenomena are
      studied as a function of magnetic field normal to the slab. In defect-free l
      texture the critical velocity for vortex nucleation is 0.5 mm/s, but in the
      presence of a domain wall it is reduced to approximately Planck's over 2pi
      /2ma(c), where a(c)(H) is the field-dependent radius of the vortex soft core. The
      vortices nucleate at a distance at least 0.3 mm from the outer edge of the disk.

PMID- 14683229
TI  - Evidence for the rare decay B-->K*l+l- and measurement of the B-->Kl+l- branching
      fraction.
AB  - We present evidence for the flavor-changing neutral current decay B-->K*l+l- and
      a measurement of the branching fraction for the related process B-->K l+l-, where
      l+l- is either an epsilon+epsilon- or a mu+mu- pair. These decays are highly
      suppressed in the standard model, and they are sensitive to contributions from
      new particles in the intermediate state. The data sample comprises 123 x 10(6)
      Upsilon(4S)-->B(-)B decays collected with the BABAR detector at the SLAC PEP-II
      epsilon+epsilon- storage ring. Averaging over K(*) isospin and lepton flavor, we
      obtain the branching fractions B(B-->Kl+l-)=(0.65(+0.14)(-0.13)+/-0.04)x10(-6)
      and B(B-->K*l+l-)=(0.88(+0.33)(-0.29)+/-0.10)x10(-6), where the uncertainties are
      statistical and systematic, respectively. The significance of the B-->Kl+l-
      signal is over 8sigma, while for B-->K*l+l- it is 3.3sigma.

PMID- 14683247
TI  - Layer- and bulk-roton excitations of 4He in porous media.
AB  - We examine the energetics of bulk- and layer-roton excitations of 4He in various
      porous medial such as aerogel, Geltech, or Vycor, in order to find out what
      conclusions can be drawn from experiments on the energetics about the
      physisorption mechanism. The energy of the layer-roton minimum depends
      sensitively on the substrate strength, thus providing a mechanism for a direct
      measurement of this quantity. On the other hand, bulklike roton excitations are
      largely independent of the interaction between the medium and the helium atoms,
      but the dependence of their energy on the degree of filling reflects the internal
      structure of the matrix and can reveal features of 4He at negative pressures.
      While bulklike rotons are very similar to their true bulk counterparts, the layer
      modes are not in close relation to two-dimensional rotons and should be regarded
      as a third, completely independent kind of excitation.

PMID- 14683248
TI  - Dynamics of phason fluctuations in the i-AlPdMn quasicrystal.
AB  - We report on the study of the dynamics of long wavelength phason fluctuations in
      the i-AlPdMn icosahedral phase using coherent x-ray scattering. When measured
      with a coherent x-ray beam, the diffuse intensity due to phasons presents strong
      fluctuations or speckles pattern. From room temperature to 500 degrees C the
      speckle pattern is time independent. At 650 degrees C the time correlation of the
      speckle pattern exhibits an exponential time decay, from which a characteristic
      time tau is extracted. We find that tau is proportional to the square of the
      phason wavelength, which demonstrates that phasons are collective diffusive modes
      in quasicrystals, in agreement with theoretical predictions.

PMID- 14683249
TI  - Short-pulse laser ablation of solids: from phase explosion to fragmentation.
AB  - The mechanisms of laser ablation in silicon are investigated close to the
      threshold energy for pulse durations of 500 fs and 50 ps. This is achieved using
      a unique model coupling carrier and atom dynamics within a unified Monte Carlo
      and molecular-dynamics scheme. Under femtosecond laser irradiation, isochoric
      heating and rapid adiabatic expansion of the material provide a natural pathway
      to phase explosion. This is not observed under slower, nonadiabatic cooling with
      picosecond pulses where fragmentation of the hot metallic fluid is the only
      relevant ablation mechanism.

PMID- 14683250
TI  - Stochastic analysis and regeneration of rough surfaces.
AB  - We investigate the Markov property of rough surfaces. Using stochastic analysis,
      we characterize the complexity of the surface roughness by means of a Fokker
      Planck or Langevin equation. The obtained Langevin equation enables us to
      regenerate surfaces with similar statistical properties compared with the
      observed morphology by atomic force microscopy.

PMID- 14683251
TI  - Electronic excitation and dynamic promotion of a surface reaction.
AB  - The mechanism of recombinative desorption of hydrogen from a Ru(0001) surface
      induced by femtosecond-laser excitation has been investigated and compared to
      thermally initiated desorption. For the laser-driven process, it is shown that
      hot substrate electrons mediate the reaction within a few hundred femtoseconds
      resulting in a huge isotope effect between H2 and D2 in the desorption yield. In
      mixed saturation coverages, this ratio crucially depends on the proportions of H
      and D. Deviations from second order desorption kinetics demonstrate that the
      recombination is dynamically promoted by excitation of neighboring, but
      nonreacting adatoms. A concentration dependent rate constant which accounts for
      the faster excitation of H versus D is proposed.

PMID- 14683252
TI  - From meandering to faceting, is step flow growth ever stable?
AB  - Based on helium atom beam diffraction and scanning tunneling microscopy data, the
      coexistence of a meandering and a bunching instability during homoepitaxial step
      flow growth is established in a class of nonreconstructed, metallic vicinal
      surfaces, Cu (1,1,n), n=5,9,17. Specifically, the meandering instability is shown
      to act as a precursor to the bunching instability, indicating that a one
      dimensional treatment of bunching in step flow growth is not sufficient. Our
      findings might be generic to step flow growth in kinetically restricted systems.

PMID- 14683253
TI  - Dynamic roughening of tetrahedral amorphous carbon.
AB  - The roughness of tetrahedral amorphous carbon (ta-C) films grown at room
      temperature is measured as a function of film thickness by atomic force
      microscopy, to extract roughness and growth exponents of alpha approximately 0.39
      and beta approximately 0-0.1, respectively. This extremely small growth exponent
      shows that some form of surface diffusion and relaxation operates at a homologous
      temperature of 0.07, much lower than in any other material. This is accounted for
      by a Monte Carlo simulation, which assumes a smoothening during a thermal spike,
      following energetic ion deposition. The low roughness allows ta-C to be used as
      an ultrathin protective coating on magnetic disk storage systems with
      approximately 1 Tbit/in.(2) storage density.

PMID- 14683254
TI  - Anomalous threshold laws in quantum sticking.
AB  - It has been stated that for a short-ranged surface interaction, the probability
      of a low-energy particle sticking to a surface always vanishes as s approximately
      k with k-->0 where k=sqrt[E]. Deviations from this so-called universal threshold
      law are derived using a linear model of particle-surface scattering. The Fredholm
      theory of integral equations is used to find the global conditions necessary for
      a convergent solution. The exceptional case of a zero-energy resonance is
      considered in detail. Anomalous threshold laws, where s approximately
      k(1+alpha),alpha>0 as k-->0, are shown to arise from a soft gap in the weighted
      density of states of excitations; alpha is determined by the behavior of the
      weighted density of states near the binding energy.

PMID- 14683255
TI  - Electronic stability of magnetic Fe/Co superlattices with monatomic layer
      alternation.
AB  - We report a surprising observation that the growth of the [Fe(1 ML)/Co(1 ML)](n)
      superlattice of L1(0) structure on Cu(100) is stable only up to six atomic layers
      (n=3), which cannot be rationalized by stress arguments. Instead, first
      principles calculations reveal a transition from the L1(0) to the B2 structure
      due to the effect of dimensionality on the stability of the electronic structure
      of the superlattice. Whereas the majority-spin electrons are energetically
      insensitive to the layer thickness, the minority-spin electrons induce the
      transition at n=3.

PMID- 14683256
TI  - Self-ordering of nanofacets on vicinal SiC surfaces.
AB  - Vicinal 4H and 6H-SiC(0001) surfaces have been investigated using atomic force
      microscopy and cross-sectional high-resolution transmission electron microscopy.
      We observed the characteristic self-ordering of nanofacets on any surface,
      regardless of polytypes and vicinal angles, after gas etching at high
      temperature. Two facet planes are typically revealed: (0001) and high index
      (112;n) that are induced by equilibrium surface phase separation. A (112;n) plane
      may have a free energy minimum due to attractive step-step interactions. The
      differing ordering distances in 4H and 6H polytypes imply the existence of SiC
      polytypic dependence on nanofaceting. Thus, it should be possible to control SiC
      surface nanostructures by selecting a polytype, a vicinal angle, and an etching
      temperature.

PMID- 14683257
TI  - Mott transitions in multiorbital systems.
AB  - Using the dynamical mean field theory it is shown that interorbital Coulomb
      interactions in nonisotropic multiorbital materials give rise to a single Mott
      transition. Nevertheless, narrow and wide subbands exhibit different excitation
      spectra in the metallic and insulating phases. The close analogy between
      "multigap" insulating behavior and multigap superconductivity is pointed out.

PMID- 14683258
TI  - Role of electronic versus atomic relaxations in Stokes shifts at defects in
      solids.
AB  - Redshifts of luminescence relative to optical absorption bands (Stokes shifts) of
      molecules and of defects in solids are universally attributed to slow atomic
      relaxations on the grounds that electronic transitions are fast (Franck-Condon
      principle). Here we report a novel phenomenon that can occur only in the solid
      state: Stokes shifts caused by slow electronic relaxations. We demonstrate that
      the phenomenon occurs in the nonbridging oxygen defect in amorphous SiO2. We
      predict that another defect (OH group), which can exist in either crystalline or
      amorphous SiO2, has a similar Stokes shift, but it arises from a mix of lattice
      and electronic relaxations with manifest differences in the two phases.

PMID- 14683259
TI  - Noninteracting electrons and the metal-insulator transition in two dimensions
      with correlated impurities.
AB  - While standard scaling arguments show that a system of noninteracting electrons
      in two dimensions and in the presence of uncorrelated disorder is insulating, in
      this paper we discuss the case where interimpurity correlations are included. We
      find that for pointlike impurities and an infinite interimpurity correlation
      length, a mobility edge exists in 2D even if the individual impurity potentials
      are random. In the uncorrelated system we recover the scaling results, while in
      the intermediate regime for length scales comparable to the correlation length,
      the system behaves like a metal but with increasing fluctuations, before strong
      localization eventually takes over for length scales much larger than the
      correlation length. In the intermediate regime, the relevant length scale is
      given by the interimpurity correlation length, with important consequences for
      high mobility systems.

PMID- 14683260
TI  - Fine structure of effective mass acceptors in gallium nitride.
AB  - Magnetoluminescence of the exciton bound to a neutral acceptor was measured to
      investigate the electronic structure of a shallow acceptor center in GaN. The
      application of magnetic fields along different directions with respect to the
      crystal c axis allowed us to determine the symmetry of the ground (Gamma(9)) and
      the first excited state (Gamma(7)) of the acceptor. The observed Zeeman splitting
      pattern has axial symmetry but can be explained well only by assuming a
      significant reduction of the spin-orbit interaction for this acceptor state.
      Because of this reduction, the energy structure of the neutral acceptor is found
      to be very sensitive to any local, axial perturbation.

PMID- 14683261
TI  - Quantum oscillations in the layer structure of thin metal films.
AB  - Understanding the underlying physical principles that determine the internal
      structure of objects at the atomic scale is critical for the advancement of
      nanoscale science. We have performed synchrotron x-ray diffraction studies to
      determine the structural properties of smooth Pb films with varying thicknesses
      of 6 to 18 monolayers deposited on a Si(111) substrate at 110 K. We observe
      quasibilayer variations in the atomic interlayer spacings of the films consistent
      with charge density oscillations due to quantum confinement of conduction
      electrons and surface-interface interference effects. Quantum oscillations in
      atomic step height are also deduced.

PMID- 14683262
TI  - Cyclotron-resonance harmonics in the ac response of a 2D electron gas with smooth
      disorder.
AB  - The frequency-dependent conductivity sigma(xx)(omega) of 2D electrons subjected
      to a transverse magnetic field and smooth disorder is calculated. The interplay
      of Landau quantization and disorder scattering gives rise to an oscillatory
      structure that survives in the high-temperature limit. The relation to recent
      experiments on photoconductivity by Zudov et al. and Mani et al. is discussed.

PMID- 14683263
TI  - One-dimensional gapless magnons in a single anisotropic ferromagnetic nanolayer.
AB  - Gapless magnons in a plane ferromagnet with normal axis anisotropy are shown to
      exist besides the usual gapped modes that affect spin dependent transport
      properties only above a finite temperature. These magnons are one-dimensional
      objects, in the sense that they are localized inside the domain walls that form
      in the film. They may play an essential role in the spin dependent scattering
      processes even down to very low temperatures.

PMID- 14683264
TI  - Coherent manipulation of electronic States in a double quantum dot.
AB  - We investigate coherent time evolution of charge states (pseudospin qubit) in a
      semiconductor double quantum dot. This fully tunable qubit is manipulated with a
      high-speed voltage pulse that controls the energy and decoherence of the system.
      Coherent oscillations of the qubit are observed for several combinations of many
      body ground and excited states of the quantum dots. Possible decoherence
      mechanisms in the present device are also discussed.

PMID- 14683265
TI  - Radiation-induced magnetoresistance oscillation in a two-dimensional electron gas
      in Faraday geometry.
AB  - Microwave-radiation induced giant magnetoresistance oscillations recently
      discovered in high-mobility two-dimensional electron systems are analyzed
      theoretically. Multiphoton-assisted impurity scatterings are shown to be the
      primary origin of the oscillation. Based on a theory which considers the
      interaction of electrons with electromagnetic fields and the effect of the
      cyclotron resonance in Faraday geometry, we are able not only to reproduce the
      correct period, phase, and the negative resistivity of the main oscillation, but
      also to predict the secondary peaks and additional maxima and minima observed in
      the experiments. These peak-valley structures are identified to relate,
      respectively, to single-, double-, and triple-photon processes.

PMID- 14683266
TI  - Critical disorder and phase transitions in random diode arrays.
AB  - Random diode arrays represent a new class of nonlinear disordered systems related
      to the physics of thin-film semiconductor structures and some others. When a
      disorder strength grows through a certain critical value, they undergo a phase
      transition from almost uniform to strongly nonuniform random electric potential.
      A piecewise continuous topography of random potential is predicted.

PMID- 14683267
TI  - Induced magnetic ordering by proton irradiation in graphite.
AB  - We provide evidence that proton irradiation of energy 2.25 MeV on highly oriented
      pyrolytic graphite samples triggers ferro- or ferrimagnetism. Measurements
      performed with a superconducting quantum interferometer device and magnetic force
      microscopy reveal that the magnetic ordering is stable at room temperature.

PMID- 14683268
TI  - Oxygen stripes in La0.5Ca0.5MnO3 from ab initio calculations.
AB  - We investigate the electronic, magnetic, and orbital properties of La0.5Ca0.5MnO3
      perovskite by means of an ab initio electronic structure calculation within the
      Hartree-Fock approximation. Using the experimental crystal structure reported by
      Radaelli et al. [Phys. Rev. B 55, 3015 (1997)]], we find a charge-ordering
      stripelike ground state. The periodicity of the stripes, and the insulating
      magnetic structure, consisting of antiferromagnetically coupled zigzag chains,
      are in agreement with neutron x-ray and electron diffraction experiments.
      However, the detailed structure is more complex than that envisaged by simple
      models of charge and orbital order on Mn d levels alone, and is better described
      as a charge-density wave of oxygen holes, coupled to the Mn spin/orbital order.

PMID- 14683269
TI  - Spin quantum tunneling via entangled states in a dimer of exchange-coupled single
      molecule magnets.
AB  - A new family of supramolecular, antiferromagnetically exchange-coupled dimers of
      single-molecule magnets (SMMs) has recently been reported. Each SMM acts as a
      bias on its neighbor, shifting the quantum tunneling resonances of the individual
      SMMs. Hysteresis loop measurements on a single crystal of SMM dimers have now
      established quantum tunneling of the magnetization via entangled states of the
      dimer. This shows that the dimer really does behave as a quantum mechanically
      coupled dimer, and also allows the measurement of the longitudinal and transverse
      superexchange coupling constants.

PMID- 14683270
TI  - Effect of zero- to one-dimensional transformation on multiparticle Auger
      recombination in semiconductor quantum rods.
AB  - We study the effect of the zero- to one-dimensional (1D) transformation on
      multiparticle Auger recombination using a series of elongated semiconductor
      nanocrystals (quantum rods). We observe a transition from the three- to two
      particle recombination process as the nanocrystal aspect ratio is increased. This
      transition indicates that in the 1D confinement limit, Auger decay is dominated
      by Coulomb interactions between 1D excitons that recombine in a bimolecular
      fashion. One consequence of this effect is strongly reduced decay rates of higher
      multiparticle states that lead to increased optical-gain lifetimes and efficient
      light amplification due to involvement of excited electronic states.

PMID- 14683271
TI  - Self-similar chain of metal nanospheres as an efficient nanolens.
AB  - As an efficient nanolens, we propose a self-similar linear chain of several metal
      nanospheres with progressively decreasing sizes and separations. To describe such
      systems, we develop the multipole spectral expansion method. Optically excited,
      such a nanolens develops the nanofocus ("hottest spot") in the gap between the
      smallest nanospheres, where the local fields are enhanced by orders of magnitude
      due to the multiplicative, cascade effect of its geometry and high Q factor of
      the surface plasmon resonance. The spectral maximum of the enhancement is in the
      near-ultraviolet region, shifting toward the red region as the separation between
      the spheres decreases. The proposed system can be used for nanooptical detection,
      Raman characterization, nonlinear spectroscopy, nanomanipulation of single
      molecules or nanoparticles, and other applications.

PMID- 14683272
TI  - Coherent optical phonons and parametrically coupled magnons induced by
      femtosecond laser excitation of the Gd(0001) surface.
AB  - Coherent spin dynamics in the THz domain coupled to a coherent phonon is observed
      in the time-resolved second harmonic response of the Gd(0001) ferromagnetic metal
      surface. An LO phonon of 2.9 THz is excited by a transient charge displacement at
      the surface caused by resonant absorption of a fs laser pulse in the exchange
      split surface state. This lattice vibration modulates the interlayer distance
      inducing a coherent variation of the exchange interaction between spins in
      adjacent layers. The resulting magnetization dynamics is considered as optical
      magnon wave packets coupled to the phonon.

PMID- 14683273
TI  - Detection of entanglement with polarized photons: experimental realization of an
      entanglement witness.
AB  - We report on the first experimental realization of an entanglement witness, a
      method to detect entanglement with few local measurements. The present
      demonstration has been performed with polarized photons in Werner states, a well
      known family of mixed states that can be either separable or nonseparable. The
      Werner states are generated by a novel high brilliance source of bipartite
      entangled states by which the state mixedness can be easily adjusted.

PMID- 14683274
TI  - Concentration of higher dimensional entanglement: qutrits of photon orbital
      angular momentum.
AB  - Enhancement of entanglement is necessary for most quantum communication protocols
      many of which are defined in Hilbert spaces larger than 2. In this work we
      present the experimental realization of entanglement concentration of orbital
      angular momentum entangled photons. We investigate the specific case of three
      dimensions and the possibility of generating different entangled states out of an
      initial state. The results presented here are of importance for pure states as
      well as for mixed states.

PMID- 14683275
TI  - Long range correlations in DNA: scaling properties and charge transfer
      efficiency.
AB  - We address the relation between long-range correlations and charge transfer
      efficiency in aperiodic artificial or genomic DNA sequences. Coherent charge
      transfer through the highest occupied molecular orbital states of the guanine
      nucleotide is studied using the transmission approach, and the focus is on how
      the sequence-dependent backscattering profile can be inferred from correlations
      between base pairs.

PMID- 14683276
TI  - Comment on "Unexpected behavior of heavy-ion fusion cross sections at extreme sub
      barrier energies".

PMID- 14683278
TI  - Comment on "Universal scaling laws of diffusion in a binary fluid mixture".

PMID- 14683280
TI  - Comment on "Disorder induced quantum phase transition in random-exchange spin-1/2
      chains".

PMID- 14683281
TI  - Quantum states far from the energy eigenstates of any local Hamiltonian.
AB  - What quantum states are possible energy eigenstates of a many-body Hamiltonian?
      Suppose the Hamiltonian is nontrivial, i.e., not a multiple of the identity, and
      L local, in the sense of containing interaction terms involving at most L bodies,
      for some fixed L. We construct quantum states psi which are "far away" from all
      the eigenstates E of any nontrivial L-local Hamiltonian, in the sense that ||psi
      E|| is greater than some constant lower bound, independent of the form of the
      Hamiltonian.

PMID- 14683282
TI  - Formation of quantum-degenerate sodium molecules.
AB  - Ultracold sodium molecules were produced from an atomic Bose-Einstein condensate
      by ramping an applied magnetic field across a Feshbach resonance. More than 10(5)
      molecules were generated with a conversion efficiency of approximately 4%. Using
      laser light resonant with an atomic transition, the remaining atoms could be
      selectively removed, preventing fast collisional relaxation of the molecules.
      Time-of-flight analysis of the pure molecular sample yielded an instantaneous
      phase-space density greater than 20.

PMID- 14683283
TI  - Decoherence and the Loschmidt echo.
AB  - Decoherence causes entropy increase that can be quantified using, e.g., the
      purity sigma=Trrho(2). When the Hamiltonian of a quantum system is perturbed, its
      sensitivity to such perturbation can be measured by the Loschmidt echo M(t). It
      is given by the squared overlap between the perturbed and unperturbed state. We
      describe the relation between the temporal behavior of sigma(t) and the average
      Mmacr;(t). In this way we show that the decay of the Loschmidt echo can be
      analyzed using tools developed in the study of decoherence. In particular, for
      systems with a classically chaotic Hamiltonian the decay of sigma and Mmacr; has
      a regime where it is dominated by the Lyapunov exponents.

PMID- 14683284
TI  - Shortcut to a Fermi-degenerate gas of molecules via cooperative association.
AB  - We theoretically examine the creation of a Fermi-degenerate gas of molecules by
      considering a photoassociation or Feshbach resonance applied to a degenerate Bose
      Fermi mixture of atoms. This problem raises interest because, unlike bosons,
      fermions in general do not behave cooperatively, so that the collective
      conversion of a degenerate gas atoms into a macroscopic number of diatomic
      molecules is not to be expected. Nevertheless, we find that the coupled Fermi
      system displays collective Rabi-like oscillations and a rapid adiabatic passage
      between atoms and molecules, thereby mimicking Bose-Einstein statistics.
      Cooperative association of a degenerate mixture of Bose and Fermi gases could
      therefore serve as a shortcut to a degenerate gas of Fermi molecules.

PMID- 14683285
TI  - Classical chaos with Bose-Einstein condensates in tilted optical lattices.
AB  - A widely accepted definition of "quantum chaos" is "the behavior of a quantum
      system whose classical limit is chaotic." The dynamics of quantum-chaotic systems
      is nevertheless very different from that of their classical counterparts. A
      fundamental reason for that is the linearity of Schrodinger equation. In this
      paper, we study the quantum dynamics of an ultracold quantum degenerate gas in a
      tilted optical lattice and show that it displays features very close to classical
      chaos. We show that its phase space is organized according to the Kolmogorov
      Arnold-Moser theorem.

PMID- 14683287
TI  - Millennium-scale sunspot number reconstruction: evidence for an unusually active
      sun since the 1940s.
AB  - The extension of the sunspot number series backward in time is of considerable
      interest for dynamo theory, solar, stellar, and climate research. We have used
      records of the (10)Be concentration in polar ice to reconstruct the average
      sunspot activity level for the period between the year 850 to the present. Our
      method uses physical models for processes connecting the (10)Be concentration
      with the sunspot number. The reconstruction shows reliably that the period of
      high solar activity during the last 60 years is unique throughout the past 1150
      years. This nearly triples the time interval for which such a statement could be
      made previously.

PMID- 14683286
TI  - Two-state theory of nonlinear stochastic resonance.
AB  - An amenable, analytical two-state description of the nonlinear population
      dynamics of a noisy bistable system driven by a rectangular subthreshold signal
      is put forward. Explicit expressions for the driven population dynamics, the
      correlation function (its coherent and incoherent parts), the signal-to-noise
      ratio (SNR), and the stochastic resonance (SR) gain are obtained. Within a
      suitably chosen range of parameter values this reduced description yields
      anomalous SR gains exceeding unity and, simultaneously, gives rise to a
      nonmonotonic behavior of the SNR vs the noise strength. The analytical results
      agree well with those obtained from numerical solutions of the Langevin equation.

PMID- 14683288
TI  - Constructing phantom cosmologies from standard scalar field universes.
AB  - We illustrate how form-invariance transformations can be used for constructing
      phantom cosmologies from standard scalar field universes. First we discuss how to
      relate two flat Friedmann-Robertson-Walker cosmologies with different barotropic
      indexes gamma and gamma;. Then we consider the particular case gamma;=-gamma, and
      we show that, if the matter content is interpreted in terms of self-interacting
      scalar fields, then the corresponding transformation provides the link between a
      standard and a phantom cosmology. After that, we illustrate the method by
      considering models with exponential potentials. Finally, we also show that the
      mentioned duality persists even if the typical brane-world modifications to the
      Friedmann equation are considered.

PMID- 14683289
TI  - J/psi polarization in 800-GeV p-Cu interactions.
AB  - We present measurements of the polarization of the J/psi produced in 800-GeV
      proton interactions with a copper target. Polarization of the J/psi is sensitive
      to the ccmacr; production and hadronization processes. A longitudinal
      polarization is observed at large x(F), while at small x(F) the state is produced
      essentially unpolarized or slightly transversely polarized. No significant
      variation of the polarization is observed versus p(T).

PMID- 14683291
TI  - Chiral solitons in nuclei: saturation, EMC effect, and Drell-Yan experiments.
AB  - The chiral quark-soliton model of the nucleon contains a mechanism for an
      attractive interaction between nucleons. This, along with the exchange of vector
      mesons between nucleons, is used to compute the saturation properties of infinite
      nuclear matter. This provides a new way to assess the effects of the nuclear
      medium on a nucleon that includes valence and sea quarks. We show that the model
      simultaneously describes the nuclear EMC effect and the related Drell-Yan
      experiments.

PMID- 14683290
TI  - B(0)-B(0) mixing in unquenched lattice QCD.
AB  - We present an unquenched lattice calculation for the B(0)-B(0) transition
      amplitude. The calculation, carried out at an inverse lattice spacing 1/a=2.22(4)
      GeV, incorporates two flavors of dynamical quarks described by the O(a)-improved
      Wilson fermion action and heavy quarks described by nonrelativistic QCD.
      Particular attention is paid to the uncertainty that arises from the chiral
      extrapolation, especially the effect of pion loops, for light quarks, which we
      find could be sizable for the leptonic decay constant, whereas it is small for
      the B parameters. We obtain f(B(d))=191(10)(+12-22) MeV,
      f(B(s))/f(B(d))=1.13(3)(+13-2), B(B(d))(m(b))=0.836(27)(+56-62),
      B(B(s))/B(B(d))=1.017(16)(+56-17), and xi=1.14(3)(+13-2), where the first error
      is statistical, and the second is systematic, including uncertainties due to
      chiral extrapolation, finite lattice spacing, heavy quark expansion, and
      perturbative operator matching.

PMID- 14683292
TI  - Charge symmetry breaking in np-->dpi(0).
AB  - The forward-backward asymmetry in np-->dpi(0), which must be zero in the center
      of-mass system if charge symmetry is respected, has been measured to be [17.2+/
      8.0(stat)+/-5.5(syst)]x10(-4), at an incident neutron energy of 279.5 MeV. This
      observable is compared to recent chiral effective field theory calculations, with
      implications regarding the du quark mass difference.

PMID- 14683293
TI  - Schiff moment of the mercury nucleus and the proton dipole moment.
AB  - We calculated the contribution of internal nucleon electric dipole moments to the
      Schiff moment of (199) Hg. The contribution of the proton electric dipole moment
      was obtained via core polarization effects that were treated in the framework of
      random phase approximation with effective residual forces. We derived a new upper
      bound |d(p)|<5.4 x 10(-24)e cm of the proton electric dipole moment.

PMID- 14683294
TI  - Creation and measurement of a coherent superposition of quantum states.
AB  - We demonstrate experimental techniques for creating and measuring a coherent
      superposition of two degenerate atomic states with equal amplitudes in metastable
      neon. Starting from state (3)P(0), we create adiabatically a coherent
      superposition of the magnetic sublevels M=+/-1 of the state (3)P(2) using a
      tripod stimulated Raman adiabatic passage scheme. The measurement is based on the
      coupling of the levels (3)P(2)<-->(3)P(1) by a linearly polarized laser, followed
      by the detection of the population in the (3)P(2)(M=+/-2) states as a function of
      the polarization angle of that laser.

PMID- 14683295
TI  - Coherence properties and quantum state transportation in an optical conveyor
      belt.
AB  - We have prepared and detected quantum coherences of trapped cesium atoms with
      long dephasing times. Controlled transport by an "optical conveyor belt" over
      macroscopic distances preserves the atomic coherence with slight reduction of
      coherence time. The limiting dephasing effects are experimentally identified, and
      we present an analytical model of the reversible and irreversible dephasing
      mechanisms. Our experimental methods are applicable at the single-atom level.
      Coherent quantum bit operations along with quantum state transport open the route
      towards a "quantum shift register" of individual neutral atoms.

PMID- 14683296
TI  - Doppler effect in resonant photoemission from SF6: correlation between Doppler
      profile and Auger emission anisotropy.
AB  - Fragmentation of the SF6 molecule upon F 1s excitation has been studied by
      resonant photoemission. The F atomiclike Auger line exhibits the characteristic
      Doppler profile that depends on the direction of the photoelectron momentum
      relative to the polarization vector of the radiation as well as on the photon
      energy. The measured Doppler profiles are analyzed by the model simulation that
      takes account of the anisotropy of the Auger emission in the molecular frame. The
      Auger anisotropy extracted from the data decreases with an increase in the F-SF5
      internuclear distance.

PMID- 14683297
TI  - Forbidden transitions in a magneto-optical trap.
AB  - We report the first observation of a nondipole transition in an ultracold atomic
      vapor. We excite the 3P-4P electric quadrupole (E2) transition in 23Na confined
      in a magneto-optical trap, and we demonstrate its application to high-resolution
      spectroscopy by making the first measurement of the hyperfine structure of the
      4P(1/2) level and extracting the magnetic dipole constant A=30.6+/-0.1 MHz. We
      use cw optical-optical double resonance accompanied by photoionization to probe
      the transition.

PMID- 14683298
TI  - Complete chemical transformation of a molecular film by subexcitation electrons
      (<3 eV).
AB  - The potential of slow electrons to act as a soft tool to control a chemical
      reaction in the condensed phase is demonstrated. By setting the energy of a well
      defined electron beam to values below 3 eV, the surface of a thin film of 1,2
      C(2)F(4)C(l2) molecules can completely be transformed into molecular chlorine
      (and by-products, possibly perfluorinated polymers). At higher energies (>6 eV)
      some equilibrium state between product and educt composition can be achieved,
      however, accompanied by a gradual overall degradation of the film. The effect of
      complete transformation is based on both the selectivity and particular energy
      dependence of the initial step of the reaction which is dissociative electron
      attachment to C(2)F(4)C(l2), but also the fact that the initial molecule is
      efficiently decomposed by subexcitation electrons while the product C(l2) is
      virtually unaffected.

PMID- 14683299
TI  - Conditional preparation of a quantum state in the continuous variable regime:
      generation of a sub-Poissonian state from twin beams.
AB  - We report the first experimental demonstration of conditional preparation of a
      nonclassical state of light in the continuous variable regime. Starting from a
      nondegenerate optical parametric oscillator which generates above threshold
      quantum intensity correlated signal and idler "twin beams," we keep the recorded
      values of the signal intensity only when the idler intensity falls inside a band
      narrower than its standard deviation. By this very simple technique, we generate
      a sub-Poissonian state 4.4 dB (64%) below shot noise from twin beams exhibiting
      7.5 dB (82%) of noise reduction in the intensity difference.

PMID- 14683300
TI  - Vacuum-field level shifts in a single trapped ion mediated by a single distant
      mirror.
AB  - A distant mirror leads to a vacuum-induced level shift in a laser-excited atom.
      This effect has been measured with a single mirror 25 cm away from a single,
      trapped barium ion. This dispersive action is the counterpart to the mirror's
      dissipative effect, which has been shown earlier to effect a change in the ion's
      spontaneous decay [Nature (London) 413, 495 (2001)]]. The experimental data are
      well described by eight-level optical Bloch equations which are amended to take
      into account the presence of the mirror according to the model in Phys. Rev. A
      66, 023816 (2002)]. Observed deviations from simple dispersive behavior are
      attributed to multilevel effects.

PMID- 14683301
TI  - Multichannel optical add-drop processes in symmetrical waveguide-resonator
      systems.
AB  - Multichannel optical add-drop processes are studied in a class of symmetric
      waveguide-resonator systems. With insight gained from group theory, we analyze
      these systems and show that they can add or drop multiple wavelengths
      simultaneously, with 100% efficiency. A new mechanism is presented to reduce the
      remnant light at the dropped wavelengths in the pass-through port. High-order
      Butterworth filters can also be achieved in these systems. Built upon
      conventional or photonic-crystal based structures, these systems can be used in
      optical communication applications.

PMID- 14683302
TI  - Light exiting from real photonic band gap crystals is diffuse and strongly
      directional.
AB  - Any photonic crystal is in practice periodic with some inevitable fabricational
      imperfections. We have measured angle-resolved transmission of photons that are
      multiply scattered by this disorder in strongly photonic crystals. Peculiar non
      Lambertian distributions occur as a function of frequency: due to internal
      diffraction, wide angular ranges of strongly reduced diffuse transmission
      coincide with photonic stop bands, while enhancements occur for directions
      outside stop gaps. We quantitatively explain the experiment with a model
      incorporating diffusion and band structure on equal footing. We predict that in
      the event of a photonic band gap, diffuse light at frequencies near band gap
      edges can exit only along isolated directions. Angle-resolved diffuse
      transmission appears to be the photonic equivalent of angle-resolved
      photoelectron spectroscopy.

PMID- 14683303
TI  - Ultrafast optical switching in three-dimensional photonic crystals.
AB  - We present the first experimental investigation of ultrafast optical switching in
      a three-dimensional photonic crystal made of a Si-opal composite. Ultrafast (30
      fs) changes in reflectivity around the photonic stop band up to 1% were measured
      for moderate pump power (70 microJ/cm(2)). Short-lived photoexcited carriers in
      silicon induce changes in the dielectric constant of Si and diminish the
      constructive interference inside the photonic crystal. The results are analyzed
      within a model based on a two-band mixing formalism.

PMID- 14683304
TI  - Multifrequency gap solitons in nonlinear photonic crystals.
AB  - We predict the existence of multifrequency gap solitons (MFGSs) in both one- and
      two-dimensional nonlinear photonic crystals. A MFGS is a single intrinsic mode
      possessing multiple frequencies inside the gap. Its existence is a result of
      synergic nonlinear coupling among solitons or soliton trains at different
      frequencies. Its formation can either lower the threshold fields of the
      respective frequency components or stabilize their excitations. These MFGSs form
      a new class of stable gap solitons.

PMID- 14683305
TI  - Effects of carrier-envelope phase differences of few-optical-cycle light pulses
      in single-shot high-order-harmonic spectra.
AB  - For the first time single-shot harmonic spectra generated by few-optical-cycle
      pulses have been measured. Clear carrier-envelope phase effects have been
      observed in the cutoff harmonic spectral structure. Results have been interpreted
      in terms of the nonadiabatic single-atom response of the nonlinear medium excited
      by few-optical-cycle pulses.

PMID- 14683306
TI  - Two-dimensional optical lattice solitons.
AB  - We study various families of two-dimensional discrete or lattice solitons, and
      show that they are possible only when their power level exceeds a critical
      threshold. In addition, we show that gap-lattice solitons exist only when the
      lattice possesses a complete 2D band gap. Our results suggest that these
      conditions are universally valid, irrespective of the nature of the nonlinearity
      or the specific structure of the index lattice. The analysis explains fundamental
      aspects of behavior of two-dimensional discrete solitons that have been very
      recently observed in photosensitive optical crystals.

PMID- 14683307
TI  - Doubly resonant IR-UV sum-frequency vibrational spectroscopy on molecular
      chirality.
AB  - We show theoretically and experimentally that for sum-frequency vibrational
      spectroscopy near electronic transitions, resonant enhancement of the chiral
      response can be much stronger than that of the achiral response. The doubly
      resonant spectrum selectively enhances the vibrational modes through their
      different electron-vibration couplings. The unusually strong resonant enhancement
      significantly improves sensitivity of chiral spectroscopy and allows detection of
      the chiral vibrational spectrum of a molecular monolayer for the first time.

PMID- 14683308
TI  - Physical mechanism of the two-dimensional enstrophy cascade.
AB  - In two-dimensional turbulence, irreversible forward transfer of enstrophy
      requires anticorrelation of the turbulent vorticity transport vector and the
      inertial-range vorticity gradient. We investigate the basic mechanism by
      numerical simulation of the forced Navier-Stokes equation. In particular, we
      obtain the probability distributions of the local enstrophy flux and of the
      alignment angle between vorticity gradient and transport vector. These are
      surprisingly symmetric and cannot be explained by a local eddy-viscosity
      approximation. The vorticity transport tends to be directed along streamlines of
      the flow and only weakly aligned down the fluctuating vorticity gradient. All
      these features are well explained by a local nonlinear model. The physical origin
      of the cascade lies in steepening of inertial-range vorticity gradients due to
      compression of vorticity level sets by the large-scale strain field.

PMID- 14683309
TI  - Lagrangian velocity statistics in turbulent flows: effects of dissipation.
AB  - We use the multifractal formalism to describe the effects of dissipation on
      Lagrangian velocity statistics in turbulent flows. We analyze high Reynolds
      number experiments and direct numerical simulation data. We show that this
      approach reproduces the shape evolution of velocity increment probability density
      functions from Gaussian to stretched exponentials as the time lag decreases from
      integral to dissipative time scales. A quantitative understanding of the
      departure from scaling exhibited by the magnitude cumulants, early in the
      inertial range, is obtained with a free parameter function D(h) which plays the
      role of the singularity spectrum in the asymptotic limit of infinite Reynolds
      number. We observe that numerical and experimental data are accurately described
      by a unique quadratic D(h) spectrum which is found to extend from h(min)
      approximately 0.18 to h(max) approximately 1.

PMID- 14683310
TI  - First spin flipping of a stored spin-1 polarized beam.
AB  - We recently studied spin flipping of a 270 MeV vertically polarized deuteron beam
      stored in the Indiana University Cyclotron Facility Cooler Ring. We adiabatically
      swept an rf solenoid's frequency through an rf-induced spin resonance and
      observed its effect on the deuterons' vector and tensor polarizations. After
      optimizing the resonance crossing rate and maximizing the solenoid's voltage, we
      measured a vector spin-flip efficiency of 94.2%+/-0.3%. We also found striking
      behavior of the spin-1 tensor polarization.

PMID- 14683311
TI  - Energetic protons from a few-micron metallic foil evaporated by an intense laser
      pulse.
AB  - With detailed experimental studies and hydrodynamics and particle-in-cell
      simulations we investigate the role of the prepulse in laser proton acceleration.
      The prepulse or pedestal (amplified spontaneous emission) can completely
      evaporate the irradiated region of a sufficiently thin foil; therefore, the main
      part of the laser pulse interacts with an underdense plasma. The multiparametric
      particle-in-cell simulations demonstrate that the main pulse generates the
      quasistatic magnetic field, which in its turn produces the long-lived charge
      separation electrostatic field, accelerating the ions.

PMID- 14683312
TI  - Liquid crystal orientation transition on microtextured substrates.
AB  - A uniform alignment of liquid crystal (LC) with finite pretilt was observed on
      microtextured substrates that were lithographically fabricated with alternating
      horizontal and vertical corrugations. As the period of alternation was decreased
      toward 0.8 microm, the nematic LC alignment on these substrates changed from
      inhomogeneous in plane, copying the substrate corrugations, to a uniform
      configuration with a large pretilt of approximately 40 degrees. This transition
      is pertinent to a frustrated boundary wherein a lowering in the LC elastic energy
      due to spatial variation in the LC orientation compromises an increase in the
      surface anchoring energy. A model based on this idea demonstrates good agreement
      with the experiment. This result may open up a new arena for tailoring substrate
      characteristics for LC alignment.

PMID- 14683313
TI  - Large structural modulations in incommensurate Te-III and Se-IV.
AB  - The high-pressure phase of tellurium, Te-III, is found to have an incommensurate
      monoclinic structure, superspace group I(')2/m(0q0)s0, of a type previously
      unknown in the elements. Te-III is stable from 4.5(2) to 29.2(7) GPa; the
      previously reported transition to a distinct Te-IV phase at 10.6 GPa is not
      observed. The incommensurate wave vector of Te-III is strongly pressure dependent
      and varies in a strongly nonlinear way. Se-IV is found to be isostructural with
      Te-III.

PMID- 14683314
TI  - Hydrogen bonding in water.
AB  - Computer simulations using density functional theory based ab initio path
      integral molecular dynamics have been carried out to investigate hydrogen bonding
      in water under ambient conditions. Structural predictions for both H2O and D2O,
      which include the effects of zero-point energy, thermal motion, and many body
      polarization effects, are contrasted with classical simulations that ignore
      nuclear quantum effects. The calculated effect of H/D isotope substitution on the
      water structure is much smaller than the difference between the classical and
      quantum path integral results, and is in excellent agreement with the measured
      H/D difference data from both neutron and x-ray scattering.

PMID- 14683315
TI  - Highly charged clusters of fullerenes: charge mobility and appearance sizes.
AB  - Clusters of fullerenes (C60,C70)(n) are produced in a gas aggregation source and
      are multiply ionized in collisions with highly charged Xe(20+,30+) ions. Their
      stabilities and decay processes are analyzed with high-resolution time-of-flight
      mass spectrometry. Fullerene clusters in charge states up to q=5 have been
      observed and appearance sizes are found to be as small as n(app)=5, 10, 21, and
      33 for q=2, 3, 4, and 5, respectively. The analysis of the multicoincident
      fragmentation spectra indicates a high charge mobility. This is in contrast to
      charge localization effects which have been reported for Ar(q+)(n) rare gas
      clusters. Clusters of fullerenes are found to be conducting when multiply
      charged.

PMID- 14683316
TI  - Nonlinear mechanical response and rippling of thick multiwalled carbon nanotubes.
AB  - The measured drop of the effective bending stiffness of multiwalled carbon
      nanotubes (MWCNTs) with increasing diameter is investigated by a generalized
      local quasicontinuum method. The previous hypothesis that this reduction is due
      to a rippling mode is confirmed by the calculations. The observed ripples result
      from a complex three-dimensional deformation similar to the Yoshimura buckling
      pattern. It is found that thick MWCNTs exhibit a well-defined nonlinear moment
      curvature relation, even for small deformations, governed by the interplay of
      strain energy relaxation and intertube interactions. Rippling deformations are
      also predicted for MWCNTs subject to torsion, resulting in an effective torsional
      modulus much smaller than that predicted by linear elasticity.

PMID- 14683317
TI  - Reconstructing complex materials via effective grain shapes.
AB  - We introduce a powerful method based on integral geometry and the Kac theorem for
      the spectrum of the Laplace operator to define the effective shape of an
      inclusion in a system made up of a distribution of arbitrarily shaped
      constituents. Reconstructing the microstructure using the effective inclusion
      shape leads to an excellent match to the percolation thresholds and to the
      mechanical and transport properties across all phase fractions. Use of the
      equivalent shape in effective medium formulations leads to good predictions. The
      method is verified for a sedimentary rock sample.

PMID- 14683318
TI  - Crack street: the cycloidal wake of a cylinder tearing through a thin sheet.
AB  - When a cylindrical tool cuts through a thin sheet of a relatively brittle
      material, it leaves behind a visually arresting crack street in its wake,
      reminiscent of a vortex street in the wake of a cylinder moving through a fluid.
      We show that simple geometrical arguments based on the interplay of in-plane
      stretching and out-of-plane bending suffice to explain the cycloidal morphology
      of the curved crack. The coupling between geometry and dynamics also allows us to
      explain the "stick-slip"-like behavior of tearing and suggests that these
      oscillations should occur generically in the brittle fracture of thin solid
      films.

PMID- 14683319
TI  - Hot and solid gallium clusters: too small to melt.
AB  - A novel multicollision induced dissociation scheme is employed to determine the
      energy content for mass-selected gallium cluster ions as a function of their
      temperature. Measurements were performed for Ga(+)(n) (n=17 39, and 40) over a 90
      720 K temperature range. For Ga+39 and Ga+40 a broad maximum in the heat capacity
      a signature of a melting transition for a small cluster-occurs at around 550 K.
      Thus small gallium clusters melt at substantially above the 302.9 K melting point
      of bulk gallium, in conflict with expectations that they will remain liquid to
      below 150 K. No melting transition is observed for Ga+17.

PMID- 14683320
TI  - Dewetting near the glass transition: transition from a capillary force dominated
      to a dissipation dominated regime.
AB  - Dynamics and corresponding morphology of dewetting of thin polystyrene films at
      temperatures close to the glass transition were investigated by measuring
      simultaneously dewetted distance and width of the rim. Comparing the opening of
      cylindrical holes with the retraction of a straight contact line revealed (i). a
      drastic influence of the geometry (planar or radial symmetry) on the dynamics at
      early stages, (ii). a new logarithmic dewetting regime, and (iii). transitions
      between four dewetting regimes clearly indicated by changes in the shape of the
      rim. The complete dewetting scenario can be understood as an initial dominance of
      capillary driving forces, which is progressively overtaken by dissipation related
      to the increasing size of the rim.

PMID- 14683321
TI  - Covalent and reversible short-range electrostatic imaging in noncontact atomic
      force microscopy.
AB  - We present a computational study of atomic-scale image formation in noncontact
      atomic force microscopy on metallic surfaces. We find two imaging scenarios: (1).
      atomic resolution arising due to very strong covalent tip-sample interaction
      exhibiting striking similarity with the imaging mechanism found on semiconductor
      surfaces, and (2). a completely new mechanism, reversible short-range
      electrostatic imaging, arising due to subtle charge-transfer interactions.
      Contrary to the strong covalent-bond imaging, the newly identified mechanism
      causes only negligible surface perturbation and can account for results recently
      observed experimentally.

PMID- 14683322
TI  - Angle-resolved mapping of the fermi velocity in a quasi-two-dimensional organic
      conductor.
AB  - We demonstrate a new method for determining the Fermi velocity in quasi-two
      dimensional (Q2D) conductors. Application of a magnetic field parallel to the
      conducting layers results in periodic open orbit quasiparticle trajectories along
      the Q2D Fermi surface. Averaging of this motion over the Fermi surface leads to a
      resonance in the interlayer microwave conductivity. The resonance frequency is
      simply related to the extremal value of the Fermi velocity perpendicular to the
      applied field. Thus, angle dependent microwave studies enable a complete mapping
      of the in-plane Fermi velocity. We illustrate the applicability of this method
      for the highly 2D organic conductor kappa-(BEDT-TTF)2I3.

PMID- 14683323
TI  - Unification of the hole transport in polymeric field-effect transistors and light
      emitting diodes.
AB  - A systematic study of the hole mobility in hole-only diodes and field-effect
      transistors based on poly(2-methoxy-5-(3('),7(')-dimethyloctyloxy)-p-phenylene
      vinylene) and on amorphous poly(3-hexyl thiophene) has been performed as a
      function of temperature and applied bias. The experimental hole mobilities
      extracted from both types of devices, although based on a single polymeric
      semiconductor, can differ by 3 orders of magnitude. We demonstrate that this
      apparent discrepancy originates from the strong dependence of the hole mobility
      on the charge carrier density in disordered semiconducting polymers.

PMID- 14683324
TI  - Very large magnetoresistance in lateral ferromagnetic (Ga,Mn)as wires with
      nanoconstrictions.
AB  - We have fabricated (Ga,Mn)As nanostructures in which domain walls can be pinned
      by sub-10 nm constrictions. Controlled by shape anisotropy, we can switch the
      regions on either side of the constriction to either parallel or antiparallel
      magnetization. All samples exhibit a positive magnetoresistance, consistent with
      domain-wall trapping. For metallic samples, we find a magnetoresistance up to 8%,
      which can be understood from spin accumulation. In samples where, due to
      depletion at the constriction, a tunnel barrier is formed, we observe a
      magnetoresistance of up to 2000%.

PMID- 14683325
TI  - Observation of non-Gaussian conductance fluctuations at low temperatures in
      Si:P(b) at the metal-insulator transition.
AB  - We report investigations of conductance fluctuations (with 1/f(alpha) power
      spectra) in doped silicon at low temperatures (T<20 K) as it is tuned through the
      metal-insulator transition (MIT) by changing the carrier concentration n. The
      scaled magnitude of noise, gamma(H), increases with decreasing T following an
      approximate power law gamma(H) approximately T-beta. At low T, gamma(H) diverges
      as n decreases through the critical concentration n(c), accompanied by a growth
      of low-frequency spectral weight. The second spectrum and probability density of
      the fluctuations show strong non-Gaussian behavior below 20 K as n/n(c) decreases
      through 1. This is interpreted as the onset of a glassy freezing of the
      electronic system across the MIT.

PMID- 14683326
TI  - Curvature-induced metallization of double-walled semiconducting zigzag carbon
      nanotubes.
AB  - We report total-energy electronic-structure calculations that provide energetics
      and electronic structures of double-walled carbon nanotubes consisting of
      semiconducting (n,0) nanotubes. We find that optimum spacing between the walls of
      the nanotubes is slightly larger than the interlayer spacing of the graphite. We
      also find that the electronic structures of the double-walled nanotubes with the
      inner (7,0) nanotube are metallic with multicarrier characters in which electrons
      and holes exist on inner and outer nanotubes, respectively. Interwall spacing and
      curvature difference are found to be essential for the electron states around the
      Fermi level.

PMID- 14683327
TI  - Critical resistance in the AlAs quantum Hall ferromagnet.
AB  - Magnetic transitions in AlAs two-dimensional electrons give rise to sharp
      resistance spikes within the quantum Hall effect. Such spikes are likely caused
      by carrier scattering at magnetic domain walls below the Curie temperature. We
      report a critical behavior in the temperature dependence of the spike width and
      amplitude, from which we deduce the Curie temperature of the quantum Hall
      ferromagnet. Our data also reveal that the Curie temperature increases
      monotonically with carrier density.

PMID- 14683328
TI  - Young's double-slit interference observation of hot electrons in semiconductors.
AB  - We have carried out Young's double-slit experiment for the hot-electron wave in
      man-made semiconductor structures with a 25-nm-space double slit in an InP layer
      buried within GaInAs, a 190-nm-thick GaInAsP hot-electron wave propagation layer,
      and a collector array of 80 nm pitch. At 4.2 K, dependences of the collector
      current on the magnetic field were measured and found to agree clearly with the
      double-slit interference theory. The present results show evidence for the wave
      front spread of hot electrons using the three-dimensional state in materials, for
      the first time, and the possibility of using top-down fabrication techniques to
      achieve quantum wave front control in materials.

PMID- 14683329
TI  - Scattering of bunched fractionally charged quasiparticles.
AB  - We report the unexpected bunching of Laughlin's quasiparticles, induced by an
      extremely weak backscattering potential at exceptionally low electron
      temperatures (T<10 mK), deduced from shot noise measurements. Backscattered
      charges q=nue, specifically, q=e/3, q=2e/5, and q<3e/7, in the respective filling
      factors, were measured. For the same settings but at a slightly higher electron
      temperature, the measured backscattered charges were q=e/3, q=e/5, and q=e/7, as
      expected. Moreover, the backscattered current exhibited distinct temperature
      dependence that was correlated to the backscattered charge and the filling
      factor. This observation suggests the existence of "low" and "high" temperature
      backscattering states, each with its characteristic charge and energy.

PMID- 14683330
TI  - Observation of bulk superconductivity in NaxCoO2.yH(2)O and NaxCoO2.yD(2)O powder
      and single crystals.
AB  - Poly- and single-crystalline NaxCoO2 has been successfully intercalated with H2O
      and D2O as confirmed by x-ray diffraction and thermogravimetric analysis.
      Resistivity, magnetic susceptibility, and specific heat measurements show bulk
      superconductivity with T(c) close to 5 K in both cases. The substitution of
      deuterium for hydrogen has an effect on T(c) of less than 0.2 K. Investigation of
      the resistivity anisotropy of NaxCoO2.yH(2)O single crystals shows (a). almost
      zero resistivity below T(c), and (b). an abrupt upturn at T(*) approximately 52 K
      in both the ab plane and the c direction. The implications of our results on the
      possible superconducting mechanism will be discussed.

PMID- 14683331
TI  - Incommensurate spin density waves in iron aluminides.
AB  - Neutron diffraction in Fe(Al) reveals incommensurate spin density waves (SDWs) in
      alloys known to be spin glasses. The wave vectors for crystals of Fe(34Al),
      Fe(40Al), and Fe(43Al) show n varying from 11 to 6 for q-->=2pi(h+/-1/n,k+/
      1/n,l+/-1/n)/a(0), where (h,k,l) and a(0) characterize the parent bcc lattice of
      the CsCl structure. The magnetic reflections are present far above the spin-glass
      freezing temperatures. These SDWs keep the spins on nearest-neighbor Fe atoms
      close to parallel, in contrast with SDWs in Cr, which keep nearest-neighbor spins
      close to antiparallel.

PMID- 14683332
TI  - Exact results for the thermal and magnetic properties of strong coupling ladder
      compounds.
AB  - We investigate the thermal and magnetic properties of the integrable su(4) ladder
      model by means of the quantum transfer matrix method. The magnetic
      susceptibility, specific heat, magnetic entropy, and high field magnetization are
      evaluated from the free energy derived via the recently proposed method of high
      temperature expansion for exactly solved models. We show that the integrable
      model can be used to describe the physics of the strong coupling ladder
      compounds. Excellent agreement is seen between the theoretical results and the
      experimental data for the known ladder compounds (5IAP)2CuBr4.2H(2)O,
      Cu2(C5H12N2)2Cl4, etc.

PMID- 14683333
TI  - Temperature dependent fluorescence in disordered Frenkel chains: interplay of
      equilibration and local band-edge level structure.
AB  - We model the optical dynamics in linear Frenkel exciton systems governed by
      scattering on static disorder and lattice vibrations and calculate the
      temperature dependent fluorescence spectrum and lifetime. The fluorescence Stokes
      shift shows a nonmonotonic behavior with temperature, which derives from the
      interplay of the local band-edge level structure and thermal equilibration. The
      model yields excellent fits to experiments performed on linear dye aggregates.

PMID- 14683334
TI  - Lattice-scale domain wall dynamics in ferroelectrics.
AB  - Ferroelectric domain walls are atomically thin, and consequently their dynamics
      are sensitive to the periodic potential of the underlying lattice. Despite their
      central role in domain dynamics, lattice-scale effects have never been directly
      observed. We investigate local domain dynamics in thin film ferroelectrics using
      atomic-force microscopy. Upon combined dc and ac electric driving, fluctuations
      in the local piezoresponse are observed. Fourier analysis of the fluctuations
      reveals the presence of narrow band and broad band noise, and Barkhausen jumps.
      The narrow band noise is attributed to dynamics associated with lattice-scale
      pinning and is reproduced by a simple physical model.

PMID- 14683335
TI  - All linear optical quantum memory based on quantum error correction.
AB  - When photons are sent through a fiber as part of a quantum communication
      protocol, the error that is most difficult to correct is photon loss. Here we
      propose and analyze a two-to-four qubit encoding scheme, which can recover the
      loss of one qubit in the transmission. This device acts as a repeater, when it is
      placed in series to cover a distance larger than the attenuation length of the
      fiber, and it acts as an optical quantum memory, when it is inserted in a fiber
      loop. We call this dual-purpose device a "quantum transponder."

PMID- 14683336
TI  - Experimental demonstration of quantum source coding.
AB  - We report an experimental demonstration of Schumacher's quantum noiseless coding
      theorem. Our experiment employs a sequence of single photons, each of which
      represents three qubits in terms of eight spatial and polarization modes. We
      initially prepare each photon in one of a set of eight nonorthogonal code word
      states corresponding to the value of a block of three binary letters. We use
      quantum coding to compress this quantum data into a two-qubit quantum channel and
      then uncompress the two-qubit channel to restore the original data with a
      fidelity approaching the theoretical limit.

PMID- 14683337
TI  - Comprehensive test of entanglement for two-level systems via the indeterminacy
      relationship.
AB  - A 3-setting Bell-type inequality enforced by the indeterminacy relation of
      complementary local observables is proposed as an experimental test of 2-qubit
      entanglement. The proposed inequality has the advantage of being a sufficient and
      necessary criterion of separability. Therefore any entangled 2-qubit state cannot
      escape the detection by this kind of test. It turns out that the orientation of
      the local testing observables plays a crucial role in our perfect detection of
      entanglement.

PMID- 14683338
TI  - Magnetic resonance realization of decoherence-free quantum computation.
AB  - We report the realization, using nuclear magnetic resonance techniques, of the
      first quantum computer that reliably executes a complete algorithm in the
      presence of strong decoherence. The computer is based on a quantum error
      avoidance code that protects against a class of multiple-qubit errors. The code
      stores two decoherence-free logical qubits in four noisy physical qubits. The
      computer successfully executes Grover's search algorithm in the presence of
      arbitrarily strong engineered decoherence. A control computer with no decoherence
      protection consistently fails under the same conditions.

PMID- 14683339
TI  - Quantum communication complexity of establishing a shared reference frame.
AB  - We discuss the aligning of spatial reference frames from a quantum communication
      complexity perspective. This enables us to analyze multiple rounds of
      communication and give several simple examples demonstrating tradeoffs between
      the number of rounds and the type of communication. Using a distributed variant
      of a quantum computational algorithm, we give an explicit protocol for aligning
      spatial axes via the exchange of spin-1/2 particles which makes no use of either
      exchanged entangled states, or of joint measurements. This protocol achieves a
      worst-case fidelity for the problem of "direction finding" that is asymptotically
      equivalent to the optimal average case fidelity achievable via a single forward
      communication of entangled states.

PMID- 14683340
TI  - Mutation accumulation in growing asexual lineages.
AB  - The stochastic loss of entire classes of individuals bearing the fewest number of
      mutations-a process known as Muller's ratchet-is studied in asexual populations
      growing unconstrained from a single founder. In the neutral regime, where
      mutations have zero effect on fitness, we derive a recursion equation for the
      probability distribution of the minimum number of mutations carried by
      individuals in the least-loaded class, and obtain an explicit condition for the
      halting of the ratchet. Next, we consider the case of deleterious mutations, and
      show that weak selection can actually accelerate the ratchet beyond that achieved
      for the neutral regime. This effect is transitory, however, as our results
      suggest that even weak purifying selection will eventually lead to the complete
      cessation of the ratchet. These results may have important implications for
      problems in biology and the medical sciences.

PMID- 14683341
TI  - Quasisoliton interaction of pursuit-evasion waves in a predator-prey system.
AB  - We consider a system of partial differential equations describing two spatially
      distributed populations in a "predator-prey" interaction with each other. The
      spatial evolution is governed by three processes: positive taxis of predators up
      the gradient of prey (pursuit), negative taxis of prey down the gradient of
      predators (evasion), and diffusion resulting from random motion of both species.
      We demonstrate a new type of propagating wave in this system. The mechanism of
      propagation of these waves essentially depends on the taxis and is entirely
      different from waves in a reaction-diffusion system. Unlike typical reaction
      diffusion waves, which annihilate on collision, these "taxis" waves can often
      penetrate through each other and reflect from impermeable boundaries.

PMID- 14683342
TI  - Charge transfer from ammonia physisorbed on nanotubes.
AB  - We report the use of nanotube field-effect transistor devices for chemical
      sensing in a conducting liquid environment. Detection of ammonia occurs through
      the shift of the gate voltage dependence of the source-drain current. We
      attribute this shift to charge transfer from adsorbed ammonia molecules, with the
      amount of charge estimated to be as small as 40 electrons for the smallest shift
      detected. Using the concentration dependence of the response as an adsorption
      isotherm, we are able to measure the amount of charge transfer to be 0.04
      electron per ammonia molecule.

PMID- 14683343
TI  - Correlations in ballistic processes.
AB  - We investigate a class of reaction processes in which particles move
      ballistically and react upon colliding. We show that correlations between
      velocities of colliding particles play a crucial role in the long time behavior.
      In the reaction-controlled limit when particles undergo mostly elastic collisions
      and therefore are always near equilibrium, the correlations are accounted
      analytically. For ballistic aggregation, for instance, the density decays as n
      approximately t(-xi) with xi=2d/(d+3) in the reaction-controlled limit in d
      dimensions, in contrast with the well-known mean-field prediction xi=2d/(d+2).

PMID- 14683344
TI  - Comment on "triplet-to-singlet exciton formation in poly(p-phenylene-vinylene)
      light-emitting diodes".

PMID- 14683345
TI  - Comment on "triplet-to-singlet exciton formation in poly(p-phenylene-vinylene)
      light-emitting diodes".

PMID- 14683347
TI  - Subharmonics and aperiodicity in hysteresis loops.
AB  - We show that it is possible to have hysteretic behavior for magnets that does not
      form simple closed loops in steady state, but cycles multiple times before
      returning to its initial state. We show this by studying the low temperature
      dynamics of the 3D Edwards-Anderson spin glass. The specific multiple varies from
      system to system and is often quite large and increases with system size. The
      last result suggests that the magnetization could be aperiodic in the large
      system limit for some realizations of randomness. It should be possible to
      observe this phenomenon experimentally.

PMID- 14683348
TI  - New measurements of G using the measurement standards laboratory torsion balance.
AB  - This Letter presents the results of a series of measurements of the Newtonian
      gravitational constant G using the compensated torsion balance developed at the
      Measurement Standards Laboratory. Since our last published result using the
      torsion balance in the compensated mode of operation [Meas. Sci. Technol. 10, 439
      (1999)]], several improvements have been made to reduce the uncertainty in the
      final result. The new measurements have used both stainless steel and copper
      large masses. The values of G for the two sets of masses are in good agreement.
      After combining all of the measurements we get a value of G=6.673 87(0.000 27) x
      10(-11) m3 kg(-1) s(-2). This new value is 5 parts in 10(5) smaller than our
      previous published values.

PMID- 14683349
TI  - Consequences of nuclear electron capture in core collapse supernovae.
AB  - The most important weak nuclear interaction to the dynamics of stellar core
      collapse is electron capture, primarily on nuclei with masses larger than 60. In
      prior simulations of core collapse, electron capture on these nuclei has been
      treated in a highly parametrized fashion, if not ignored. With realistic
      treatment of electron capture on heavy nuclei come significant changes in the
      hydrodynamics of core collapse and bounce. We discuss these as well as the
      ramifications for the postbounce evolution in core collapse supernovae.

PMID- 14683350
TI  - Millisecond pulsars with r-modes as steady gravitational radiators.
AB  - Millisecond pulsars (MSPs) probably achieve their fast rotation by mass transfer
      from their companion stars in low-mass x-ray binaries (LMXBs). The lack of MSPs
      and LMXBs rotating near breakup has been attributed to the accretion torque being
      balanced, at fast rotation, by gravitational radiation, perhaps caused by an
      unstable oscillation mode. It has been argued that internal dissipation involving
      hyperons may cause LMXBs to evolve into a quasisteady state, with nearly constant
      rotation rate, temperature, and mode amplitude. We show that MSPs descending from
      these LMXBs spend a long time in a similar state, as extremely steady sources of
      gravitational waves and thermal x rays, while they spin down due to gravitational
      radiation and the standard magnetic torque. Observed MSP braking torques already
      place meaningful constraints on this scenario.

PMID- 14683351
TI  - N=1/2 Wess-Zumino model is renormalizable.
AB  - The Wess-Zumino model on N=1/2 nonanticommutative superspace, which contains the
      dimension-6 term F3, is shown to be renormalizable to all orders in perturbation
      theory, upon adding F and F2 terms to the original Lagrangian. The
      renormalizability is possible, even with this higher-dimension operator, because
      the Lagrangian is not Hermitian. Such deformed field theories arise naturally in
      string theory with a graviphoton background.

PMID- 14683354
TI  - Nuclear shadowing and extraction of Fp2-Fn2 at small x from deuteron collider
      data.
AB  - We demonstrate that leading twist nuclear shadowing leads to large corrections
      for the extraction of the neutron structure function Fn2 from the future deuteron
      collider data both in the inclusive and in the tagged structure function modes.
      We suggest several strategies to address the extraction of Fn2 and to measure at
      the same time the effect of nuclear shadowing via the measurement of the
      distortion of the proton spectator spectrum in the semi-inclusive eD-->e'pX
      process.

PMID- 14683355
TI  - Geometric scaling in inclusive charm production.
AB  - We show that the cross section for inclusive charm production exhibits geometric
      scaling in a large range of photon virtualities. In the DESY ep collider HERA
      kinematic domain the saturation momentum Q(2)(sat)(x) stays below the hard scale
      micro(2)(c)=4m(2)(c), implying charm production probing mostly the color
      transparency regime and unitarization effects being almost negligible. We derive
      our results considering two saturation models which are able to describe the HERA
      data for the proton structure function at small values of the Bjorken variable x.
      A striking feature is the scaling on tau identical with Q(2)/Q(2)(sat)(x) above
      te saturation limit, corroborating recent theoretical studies.

PMID- 14683352
TI  - Measurement of branching fractions and polarization in B-->phiK(*) decays.
AB  - We present the first measurement of decay amplitudes in B-->phiK* and
      measurements of branching fractions in B-->phiK(*) decays based on 78.1 fb(-1) of
      data recorded at the Upsilon(4S) resonance with the Belle detector at the KEKB
      e+e- storage ring. The decay amplitudes for the different phiK*0 helicity states
      are measured from the angular distributions of final state particles in the
      transversity basis. The longitudinal and transverse complex amplitudes are
      |A0|2=0.43+/-0.09+/-0.04, |A(perpendicular)|2=0.41+/-0.10+/-0.04,
      arg((A(parallel))=-2.57+/-0.39+/-0.09, and arg((A(perpendicular))=0.48+/-0.32+/
      0.06. The direct CP-violating asymmetries are found to be consistent with zero.

PMID- 14683357
TI  - Influence of the coulomb interaction on the liquid-gas phase transition and
      nuclear multifragmentation.
AB  - The liquid-gas phase transition is analyzed from the topologic properties of the
      event distribution in the observables space. A multicanonical formalism allows
      one to directly relate the standard phase transition with neutral particles to
      the case where the nonsaturating Coulomb interaction is present, and to interpret
      the Coulomb effect as a deformation of the probability distributions and a
      rotation of the order parameter. This formalism is applied to a statistical
      multifragmentation model and consequences for the nuclear multifragmentation
      phase transitions are drawn.

PMID- 14683358
TI  - Observation of collective friction forces due to spatial self-organization of
      atoms: from Rayleigh to Bragg scattering.
AB  - We demonstrate that emission-induced self-organization of two-level atoms can
      effect strong damping of the sample's center-of-mass motion. When illuminated by
      far-detuned light, cold cesium atoms assemble into a density grating that
      efficiently diffracts the incident light into an optical resonator. We observe
      random phase jumps of pi in the emitted light, confirming spontaneous symmetry
      breaking in the atomic self-organization. The Bragg diffraction results in a
      collective friction force with center-of-mass deceleration up to 1000 m/s(2) that
      is effective even for an open atomic transition.

PMID- 14683356
TI  - Near-threshold production of the multistrange Xi- hyperon.
AB  - The yield for the multistrange Xi(-) hyperon has been measured in 6A GeV Au+Au
      collisions via reconstruction of its decay products pi(-) and Lambda, the latter
      also being reconstructed from its daughter tracks of pi(-) and p. The measurement
      is rather close to the threshold for Xi(-) production and therefore provides an
      important test of model predictions. The measured yield for Xi(-) and Lambda are
      compared for several centralities. In central collisions the Xi(-) yield is found
      to be in excellent agreement with statistical and transport model predictions,
      suggesting that multistrange hadron production approaches chemical equilibrium in
      high baryon density nuclear matter.

PMID- 14683359
TI  - Time-domain investigation of electron recapture via post-collision interaction in
      a double photoionization continuum.
AB  - Picosecond laser pulses have been used to sequentially photoionize both valence
      electrons from neutral Ba atoms, producing two radially localized continuum wave
      packets. The Coulomb interaction between the two outgoing electrons can result in
      the recapture of one of the electrons by the parent ion. The energy distribution
      of Rydberg ions formed via this "post-collision" interaction is measured as a
      function of the delay between the ionizing laser pulses. The experimental data
      are in agreement with the results of both a quantum sudden approximation and a
      classical simulation.

PMID- 14683360
TI  - Fingerprint IR spectroscopy to probe amino acid conformations in the gas phase.
AB  - We report the infrared (IR) absorption spectra of different conformational
      isomers of gas phase amino acid molecules in the molecular fingerprint region of
      330-1500 cm(-1). The IR absorption spectra for three conformers of the amino acid
      tryptophan show absorption bands that uniquely identify the conformational
      structure of the molecule and that are well matched by density functional theory
      calculations. The present observations hold great promise for future
      identification of conformational folding of larger molecules by means of their IR
      absorption characteristics.

PMID- 14683361
TI  - Internal laser-induced dipole force at work in C60 molecule.
AB  - We show how the many electron response of a complex molecule to an intense laser
      field can be incorporated with the single active electron picture. This enables
      us to introduce an "over-the-barrier" model for Cz+60 ionization, valid for long
      wavelength light. Using infrared radiation, we confirm the model and also produce
      stable, highly charged C60 reaching C12+60, the highest charge state ever
      observed. At high intensities and high charge states the internal laser-induced
      dipole force and rapid charging lead to stress on the molecule. The interplay
      between the forces provides control and suggest strategies for reaching even
      higher charge states.

PMID- 14683362
TI  - Information capacity of optical fiber channels with zero average dispersion.
AB  - We study the statistics of optical data transmission in a noisy nonlinear fiber
      channel with a weak dispersion management and zero average dispersion. Applying
      analytical expressions for the output probability density functions both for a
      nonlinear channel and for a linear channel with additive and multiplicative noise
      we calculate in a closed form a lower bound estimate on the Shannon capacity for
      an arbitrary signal-to-noise ratio.

PMID- 14683363
TI  - Unique phase recovery for nonperiodic objects.
AB  - It is well known that the loss of phase information at detection means that a
      diffraction pattern may be consistent with a multitude of physically different
      structures. This Letter shows that it is possible to perform unique structural
      determination in the absence of a priori information using x-ray fields with
      phase curvature. We argue that significant phase curvature is already available
      using modern x-ray optics and we demonstrate an algorithm that allows the phase
      to be recovered uniquely and reliably.

PMID- 14683364
TI  - Measurement of local field effects of the host on the lifetimes of embedded
      emitters.
AB  - We report experimental results on the variation of the radiative lifetime of Eu3+
      ion embedded in a dielectric with the refractive index n. We dope 1 mol % of Eu3+
      into the binary glass system xPbO-(1-x)B2O3. By varying x we have achieved a
      fairly large variation of the refractive index from 1.7 to 2.2. This enables us
      to study the local field effects for the first time for ions doped in a solid
      glassy material. Our measurements are in agreement with the so-called real cavity
      model. The present measurements are free from the complications arising from
      reorganizational effects in solvents.

PMID- 14683365
TI  - Global nature of dilute-to-dense transition of granular flows in a 2D channel.
AB  - The dilute-to-dense transition of granular flow of particle size d(0) is studied
      experimentally in a two-dimensional channel (width D) with confined exit (width
      d). Our results show that with fixed d and D there is a maximum inflow rate Q(c)
      above which the flow changes from dilute to dense and the outflow rate <Q(t)>
      drops abruptly from Q(c) to a dense rate Q(d). A rescaled critical rate q(c) is
      found to be a function of a scaling variable lambda only: q(c) approximately
      F(lambda), where lambda identical with d/d(0) d/D-d. This form of lambda suggests
      that the dilute-to-dense transition is a global property of the flow, unlike the
      jamming transition which depends only on d/d(0). Furthermore, the transition is
      found to occur when the area fraction of particles near the exit exceeds a
      critical value which is close to 0.65+/-0.03.

PMID- 14683366
TI  - Focusing x-ray beams to nanometer dimensions.
AB  - We address the question: what is the smallest spot size to which an x-ray beam
      can be focused? We show that confinement of the beam within a narrowly tapered
      waveguide leads to a theoretical minimum beam size of the order of 10 nm (FWHM),
      the exact value depending only on the electron density of the confining material.
      This limit appears to apply to all x-ray focusing devices. Mode mixing and
      interference can help to achieve this spot size without the need for ultrasmall
      apertures.

PMID- 14683367
TI  - Demonstration of a collisionally excited optical-field-ionization XUV laser
      driven in a plasma waveguide.
AB  - We describe the first demonstration of a collisionally excited optical-field
      ionization laser driven within a waveguide. Lasing on the 4d(9)5d-4d(9)5p
      transition at 41.8 nm in Xe8+ was observed to be closely correlated to conditions
      under which the pump laser pulses were guided well by a gas-filled capillary
      discharge waveguide. Simulations of the propagation of the pump laser radiation
      show that gain was achieved over essentially the whole 30 mm length of the
      waveguide.

PMID- 14683368
TI  - Investigation of current-density modification during magnetic reconnection by
      analysis of hydrogen-pellet deflection.
AB  - A pellet penetrating the inner region of a tokamak discharge, where the safety
      factor drops below unity, triggers an instability analogous to a sawtooth crash.
      Because of the simultaneity of the crash and pellet crossing, the latter is an
      appropriate probe for investigating the current distribution during reconnection.
      In this Letter, pellet deflection is used to characterize the associated electron
      distribution function. The perturbation compatible with the observed trajectory
      requires a negative current layer on the q=1 magnetic surface between 3 and 12
      times the equilibrium current density and an expulsion of high energy electrons
      from the plasma core.

PMID- 14683369
TI  - Observation of anomalous momentum transport in tokamak plasmas with no momentum
      input.
AB  - Anomalous momentum transport has been observed in Alcator C-Mod tokamak plasmas
      through analysis of the time evolution of core impurity toroidal rotation
      velocity profiles. Following the L-mode to EDA (enhanced D(alpha)) H-mode
      transition, the ensuing cocurrent toroidal rotation velocity, which is generated
      in the absence of any external momentum source, is observed to propagate in from
      the edge plasma to the core. The steady state toroidal rotation velocity profiles
      are relatively flat and the momentum transport can be simulated with a simple
      diffusion model. Velocity profiles during edge localized mode free (ELM-free) H
      modes are centrally peaked, which suggests the addition of inward momentum
      convection. In all operating regimes the observed momentum diffusivities are much
      larger than the neoclassical values.

PMID- 14683371
TI  - Pair-ion plasma generation using fullerenes.
AB  - We have developed a novel method for generating pure pair plasma which consists
      of positive- and negative-charged particles with an equal mass. The pair-ion
      plasma without electrons is generated using fullerene as an ion source through
      the processes of hollow-electron-beam impact ionization, electron attachment,
      preferential radial diffusion of ions, and resultant electron separation in an
      axial magnetic field. Basic characteristics of this plasma are discussed in terms
      of the differences from ordinary electron-ion plasmas, such as a phenomenon in
      the absence of sheath and potential structure formation.

PMID- 14683370
TI  - Current drive in a ponderomotive potential with sign reversal.
AB  - Noninductive current drive can be accomplished through ponderomotive forces with
      high efficiency when the potential changes sign over the interaction region. The
      effect, which operates somewhat like a Maxwell demon, can be practiced upon both
      ions and electrons. The current-drive efficiencies, in principle, might be higher
      than those possible with conventional rf current-drive techniques. It remains,
      however, for us to identify how the effect might be implemented in a magnetic
      fusion device in a practical manner.

PMID- 14683372
TI  - Transformations in the medium-range order of fused silica under high pressure.
AB  - Molecular dynamics simulations of fused silica at shock pressures reproduce the
      experimental equation of state of this material and explain its characteristic
      shape. We demonstrate that shock waves modify the medium-range order of this
      amorphous system, producing changes that are only clearly revealed by its ring
      size distribution. The ring size distribution remains practically unchanged
      during elastic compression but varies continuously after the transition to the
      plastic regime.

PMID- 14683373
TI  - Evidence of the Zn vacancy acting as the dominant acceptor in n-type ZnO.
AB  - We have used positron annihilation spectroscopy to determine the nature and the
      concentrations of the open volume defects in as-grown and electron irradiated
      (E(el)=2 MeV, fluence 6 x 10(17) cm(-2)) ZnO samples. The Zn vacancies are
      identified at concentrations of [V(Zn)] approximately 2 x 10(15) cm(-3) in the as
      grown material and [V(Zn)] approximately 2 x 10(16) cm(-3) in the irradiated ZnO.
      These concentrations are in very good agreement with the total acceptor density
      determined by temperature dependent Hall experiments. Thus, the Zn vacancies are
      dominant acceptors in both as-grown and irradiated ZnO.

PMID- 14683353
TI  - Measurements of branching fractions and CP-violating asymmetries in B0-->rho(+/
      )h(-/+) decays.
AB  - We present measurements of branching fractions and CP-violating asymmetries in B0
      ->rho(+/-)pi(-/+) and B0-->rho-K+ decays. The results are obtained from a data
      sample of 88.9 x 10(6) Upsilon(4S)-->BB decays collected with the BABAR detector
      at the SLAC PEP-II asymmetric-energy B Factory. From a time-dependent maximum
      likelihood fit we measure the branching fractions B(B0-->rho(+/-)pi(-/+))=[22.6+/
      1.8 (stat)+/-2.2 (syst)]x10(-6) and B(B0-->rho-K+)=(7.3 -1.2( +1.3)+/-1.3)x10(
      6), and the CP-violating charge asymmetries A(rhopi)(CP)=-0.18+/-0.08+/-0.03 and
      A(rhoK)(CP)=0.28+/-0.17+/-0.08, the direct CP violation parameter C(rhopi)=0.36+/
      0.18+/-0.04 and the mixing-induced CP violation parameter S(rhopi)=0.19+/-0.24+/
      0.03, and the dilution parameters DeltaC(rhopi)=0.28 -0.19( +0.18)+/-0.04 and
      DeltaS(rhopi)=0.15+/-0.25+/-0.03.

PMID- 14683374
TI  - Helical gold nanotube synthesized at 150 K.
AB  - Gold nanowires were synthesized at 150 K by electron beam thinning of a gold thin
      foil in an UHV electron microscope. The gold nanowires were found to have a
      helical multishell structure (HMS). One particular nanowire, which was thinner
      than the 7-1 HMS nanowire, was found to have a tubular structure. The gold single
      wall nanotube is composed of five atomic rows that coil about the tube axis. The
      diameter was 0.4 nm and the pitch was 11 nm. The stability of the (5,3) nanotube
      was discussed in terms of the shear deformation of the triangular network of gold
      atoms.

PMID- 14683375
TI  - Coarsening of fractal viscous fingering patterns.
AB  - We have measured the coarsening due to surface tension of radially grown fractal
      viscous fingering patterns. The patterns at late times depend on the structural
      form at the onset of coarsening, providing information on the age of the fractal.
      The coarsening process is not dynamically scale invariant, exhibiting two dynamic
      length scales that grow as L1(t) approximately t(0.22+/-0.02) and L2(t)
      approximately t(0.31+/-0.02). The measured exponents are in agreement with the
      results of recent numerical studies of diffusion-controlled coarsening of a
      diffusion-limited aggregation fractal [Phys. Rev. E 65, 050501 (2002)]].

PMID- 14683376
TI  - Experimental electronic heat capacities of alpha- and delta-plutonium: heavy
      fermion physics in an element.
AB  - We have measured the heat capacities of delta-Pu0.95Al0.05 and alpha-Pu over the
      temperature range 2-303 K. The availability of data below 10 K plus an estimate
      of the phonon contribution to the heat capacity based on recent neutron
      scattering experiments on the same sample enable us to make a reliable deduc-tion
      of the electronic contribution to the heat capacity of delta-Pu0.95Al0.05; we
      find gamma=64+/-3 mJ K(-2) mol(-1) as T-->0. This is larger than that of any
      element and large enough for delta-Pu0.95Al0.05 to be classed as a heavy-fermion
      system. By contrast, gamma=17+/-1 mJ K(-2) mol(-1) in alpha-Pu. Two distinct
      anomalies are seen in the electronic contribution to the heat capacity of delta
      Pu0.95Al0.05, one or both of which may be associated with the formation of the
      alpha(')-martensitic phase. We suggest that the large gamma value of delta
      Pu0.95Al0.05 may be caused by proximity to a quantum-critical point.

PMID- 14683377
TI  - Self-doping of gold chains on silicon: a new structural model for Si(111)-(5 x 2)
      Au.
AB  - A new structural model for the Si(111)-(5 x 2)-Au reconstruction is proposed and
      analyzed using first-principles calculations. The basic model consists of a
      "double honeycomb chain" decorated by Si adatoms. The 5 x 1 periodicity of the
      honeycomb chains is doubled by the presence of a half-occupied row of Si atoms
      that partially rebonds the chains. Additional adatoms supply electrons that dope
      the parent band structure and stabilize the period doubling; the optimal doping
      corresponds to one adatom per four 5 x 2 cells, in agreement with experiment. All
      the main features observed in scanning tunneling microscopy and photoemission are
      well reproduced.

PMID- 14683378
TI  - Site determination and thermally assisted tunneling in homogenous nucleation.
AB  - A combined low-temperature scanning tunneling microscopy and density functional
      theory study on the binding and diffusion of copper monomers, dimers, and trimers
      adsorbed on Cu(111) is presented. Whereas atoms in trimers are found in fcc sites
      only, monomers as well as atoms in dimers can occupy the fcc as well as the
      metastable hcp site. In fact the dimer fcc-hcp configuration is only 1.3 meV less
      favorable with respect to the fcc-fcc configuration. This enables a confined
      intracell dimer motion, which at temperatures below 5 K is dominated by thermally
      assisted tunneling.

PMID- 14683379
TI  - Effects of strain on the dissociation dynamics of O2 on Si(001).
AB  - There are two distinctive channels in the dissociation reaction of O2 on Si(001)
      (2 x 1): a trapping-mediated channel and a direct-activated channel. Externally
      applied tensile strain along the <110> direction on the (001) surface is found to
      suppress the dissociation via a direct-activated channel and to enhance that via
      a trapping-mediated channel in the temperature range between 200 and 300 K. It
      has been demonstrated that the dissociation dynamics involving elementary
      processes such as inelastic scattering and trapping, desorption and/or
      dissociation from a trapping precursor, and direct dissociation are sensitively
      influenced by the strain to change the branching ratio of the dissociation
      reaction.

PMID- 14683380
TI  - Changing the diffusion mechanism of Ge-Si dimers on Si(001) using an electric
      field.
AB  - We change the diffusion mechanism of adsorbed Ge-Si dimers on Si(001) using the
      electric field of a scanning tunneling microscope tip. By comparing the measured
      field dependence with first-principles calculations we conclude that, in negative
      field, i.e., when electrons are attracted towards the vacuum, the dimer diffuses
      as a unit, rotating as it translates, whereas, in positive field the dimer bond
      is substantially stretched at the transition state as it slides along the
      substrate. Furthermore, the active mechanism in positive fields facilitates
      intermixing of Ge in the Si lattice, whereas intermixing is suppressed in
      negative fields.

PMID- 14683381
TI  - E' centers in alpha quartz in the absence of oxygen vacancies: a first-principles
      molecular-dynamics study.
AB  - The displacement of an oxygen atom in pure alpha quartz is studied via first
      principles molecular dynamics. The simulations show that when an O atom in a Si-O
      Si bridge is moved away from its original equilibrium position, a new stable
      energy minimum can be reached. Depending on the spin state and charge Q of the
      system, this minimum can give rise to either a threefold oxygen (singlet ground
      state and Q=+1) or to an unsaturated Si atom carrying a dangling bond (triplet
      state). In the latter case, the hyperfine parameters associated with the 29Si
      dangling bond are in rather good agreement with electron paramagnetic
      resonance/electron nuclear double resonance experiments.

PMID- 14683382
TI  - Variational cluster approach to correlated electron systems in low dimensions.
AB  - A self-energy-functional approach is applied to construct cluster approximations
      for correlated lattice models. It turns out that the cluster-perturbation theory
      [Phys. Rev. Lett. 84, 522 (2000)]] and the cellular dynamical mean-field theory
      [Phys. Rev. Lett. 87, 186401 (2001)]] are limiting cases of a more general
      cluster method. The results for the one-dimensional Hubbard model are discussed
      with regard to boundary conditions, bath degrees of freedom, and cluster size.

PMID- 14683383
TI  - Junctions of three quantum wires and the dissipative Hofstadter model.
AB  - We study a junction of three quantum wires enclosing a magnetic flux. This is the
      simplest problem of a quantum junction between Tomonaga-Luttinger liquids in
      which Fermi statistics enter in a nontrivial way. We present a direct connection
      between this problem and the dissipative Hofstadter problem, or quantum Brownian
      motion in two dimensions in a periodic potential and an external magnetic field,
      which in turn is connected to open string theory in a background electromagnetic
      field. We find nontrivial fixed points corresponding to a chiral conductance
      tensor leading to an asymmetric flow of the current.

PMID- 14683384
TI  - Hopping between localized Floquet states in periodically driven quantum dots.
AB  - The dynamic localization in energy space, suppression of the absorption of energy
      from an external microwave field due to quantum interference, was analyzed
      recently for a closed quantum dot in the absence of electron-electron
      interactions. Here a weak interaction is shown to lead to a finite absorption and
      heating, which may be viewed as hopping between localized Floquet states. The
      heating rate grows together with the electronic temperature, eventually
      destroying the localization.

PMID- 14683385
TI  - Singlet-triplet transition tuned by asymmetric gate voltages in a quantum ring.
AB  - Wave-function and interaction effects in the addition spectrum of a Coulomb
      blockaded many-electron quantum ring are investigated as a function of
      asymmetrically applied gate voltages and magnetic field. Hartree and exchange
      contributions to the interaction are quantitatively evaluated at a crossing
      between states extended around the ring and states which are more localized in
      one arm of the ring. A gate tunable singlet-triplet transition of the two
      uppermost levels of this many-electron ring is identified at zero magnetic field.

PMID- 14683386
TI  - Magnetic-field-induced finite-size effect in the nigh-temperature superconductor
      YBa2Cu3O(7-delta): a comparison with rotating superfluid 4He.
AB  - The effect of strong magnetic fields (11 T) on superconductivity in YBa2Cu3O(7
      delta) is investigated using high-resolution thermal expansion. We show that the
      field-induced broadening of the superconducting transition is due to a finite
      size effect resulting from the field-induced vortex-vortex length scale. The
      physics of this broadening has recently been elucidated for the closely related
      case of rotating superfluid 4He [Phys. Rev. B 60, 12 373 (1999)]]. Our results
      imply that the primary effect of magnetic fields of the order of 10 T is to
      destroy the phase coherence; the pairing, on the other hand, appears to be quite
      insensitive to these fields.

PMID- 14683387
TI  - Magnetic excitations in the ferromagnetic superconductor UGe2.
AB  - We report that the uniform magnetization is not conserved in the magnetic
      excitation spectrum of UGe2. The measured spectrum is therefore different from
      that in d-electron ferromagnetic metals in a way that would facilitate
      magnetically mediated superconductivity.

PMID- 14683388
TI  - Pressure-induced three-dimensional ferromagnetic correlations in the giant
      magnetocaloric compound Gd5Ge4.
AB  - The giant magnetocaloric compound Gd5Ge4 is the only member of the Gd5(SixGe1-x)4
      family where three-dimensional exchange interactions between two-dimensional
      correlated layers of the crystallographic structure are so weak that spontaneous
      ferromagnetism does not set in at any temperature. In this Letter we explore the
      possibility to reach the ferromagnetic state by application of hydrostatic
      pressure. Linear thermal expansion and magnetic measurements under pressure
      reveal that the reduction of the unit cell volume induces a spatially phase
      segregated ground state below 10 kbar.

PMID- 14683389
TI  - Spin dynamics from majorana fermions.
AB  - Using the Majorana fermion representation of spin-1/2 local moments, we show how
      the dynamic spin correlation and susceptibility are obtained directly from the
      one-particle Majorana propagator. We illustrate our method by applying it to the
      spin dynamics of a nonequilibrium quantum dot, computing the voltage-dependent
      spin relaxation rate and showing that, at weak coupling, the fluctuation
      dissipation relation for the spin of a quantum dot is voltage dependent. We
      confirm the voltage-dependent Curie susceptibility recently found by Parcollet
      and Hooley [Phys. Rev. B 66, 085315 (2002)]].

PMID- 14683390
TI  - Spin-spin correlators in the majorana representation.
AB  - In the Majorana representation of a spin 1/2 we find an identity which relates
      spin-spin correlators to one-particle fermionic correlators. This should be
      contrasted with the straightforward approach in which two-particle (four-fermion)
      correlators need to be calculated. We discuss applications to the analysis of the
      dynamics of a spin coupled to a dissipative environment and of a quantum detector
      performing a continuous measurement of a qubit's state.

PMID- 14683391
TI  - Decoupling of the magnetic and structural transformations in Er5Si4.
AB  - Er5Si4 is a member of the R5(Si(4-x)Gex) family of alloys, where R=rare earth
      metal. Many of these compounds display a strong coupling between the magnetic and
      crystal lattices. In the naturally layered R5(Si(4-x)Gex) materials, inter- and
      intralayer interactions can be controlled by chemical and physical means; thus
      their physical properties can be tailored within wide limits. The Er5Si4 is
      unique in that the temperature dependent structural sequence is opposite that of
      other representatives of this family. The magnetism of Er5Si4 is reflective of
      its exceptional place within the series.

PMID- 14683392
TI  - Subwavelength resolution in a two-dimensional photonic-crystal-based superlens.
AB  - We experimentally and theoretically demonstrate single-beam negative refraction
      and superlensing in the valence band of a two-dimensional photonic crystal
      operating in the microwave regime. By measuring the refracted electromagnetic
      waves from a slab shaped photonic crystal, we find a refractive index of -1.94
      that is very close to the theoretical value of -2.06. A scanning transmission
      measurement technique is used to measure the spatial power distribution of the
      focused electromagnetic waves that radiate from a point source. The full width at
      half maximum of the focused beam is measured to be 0.21 lambda, which is in good
      agreement with the finite difference time domain method simulations. We also
      report a subwavelength resolution for the image of two incoherent point sources,
      which are separated by a distance of lambda/3.

PMID- 14683393
TI  - One-way optoelectronic switching of photochromic molecules on gold.
AB  - We investigate photochromic molecular switches that are self-assembled on gold.
      We use two experimental techniques; namely, the mechanically controllable break
      junction technique to measure electronic transport, and UV/Vis spectroscopy to
      measure absorption. We observe switching of the molecules from the conducting to
      the insulating state when illuminated with visible light (lambda=546 nm), in
      spite of the gold surface plasmon absorption present around this wavelength.
      However, we fail to observe the reverse process which should occur upon
      illumination with UV light (lambda=313 nm). We attribute this to quenching of the
      excited state of the molecule in the open form by the presence of gold.

PMID- 14683394
TI  - Response of disordered matter to electromagnetic fields.
AB  - We have studied a variety of different disordered materials, including molecular
      and ionic liquids, supercooled liquids, glasses, ionic conductors, and doped
      semiconductors, in ac electromagnetic fields over an exceptional broad dynamic
      range, including the rarely investigated GHz to THz region. All classes of
      disordered matter exhibit an astonishingly similar response: In addition to
      Jonscher's time-honored "universal dielectric response," a superlinear power-law
      increase of the frequency-dependent conductivity shows up bridging the gap
      between the classical dielectric and the infrared region. Thus the universal
      dielectric behavior of disordered matter extends up to much higher frequencies
      than thought until now.

PMID- 14683395
TI  - Local manipulation of nuclear spin in a semiconductor quantum well.
AB  - The shaping of nuclear spin polarization profiles and the induction of nuclear
      resonances are demonstrated within a parabolic quantum well using an externally
      applied gate voltage. Voltage control of the electron and hole wave functions
      results in nanometer-scale sheets of polarized nuclei positioned along the growth
      direction of the well. Applying rf voltages across the gates induces resonant
      spin transitions of selected isotopes. This depolarizing effect depends strongly
      on the separation of electrons and holes, suggesting that a highly localized
      mechanism accounts for the observed behavior.

PMID- 14683396
TI  - Muon spin relaxation and susceptibility studies of the pure and diluted spin 1/2
      kagome-like lattice system (CuxZn(1-x))3V2O7(OH2) 2H2O.
AB  - Muon spin relaxation and magnetic susceptibility measurements have been performed
      on the pure and diluted spin 1/2 kagome system (CuxZn(1-x))3V2O7(OH)2 2H2O. In
      the pure x=1 system we found a slowing down of Cu spin fluctuations with
      decreasing temperature towards T approximately 1 K, followed by slow and nearly
      temperature-independent spin fluctuations persisting down to T=50 mK, indicative
      of quantum fluctuations. No indication of static spin freezing was detected in
      either of the pure (x=1.0) or diluted samples. The observed magnitude of
      fluctuating fields indicates that the slow spin fluctuations represent an
      intrinsic property of kagome network rather than impurity spins.

PMID- 14683397
TI  - Detection and manipulation of statistical polarization in small spin ensembles.
AB  - We report the detection of the square root of N statistical polarization in a
      small ensemble of electron spin centers in SiO2 by magnetic resonance force
      microscopy. A novel detection technique was employed that captures the
      statistical polarization and cycles it between states that are either locked or
      antilocked to the effective field in the rotating frame. Using field gradients as
      high as 5 G/nm, we achieved a detection sensitivity equivalent to roughly two
      electron spins, and observed ultralong spin-lock lifetimes, as long as 20 s.
      Given a sufficient signal-to-noise ratio, this scheme should be extendable to
      single electron spin detection.

PMID- 14683398
TI  - Quantum communication through an unmodulated spin chain.
AB  - We propose a scheme for using an unmodulated and unmeasured spin chain as a
      channel for short distance quantum communications. The state to be transmitted is
      placed on one spin of the chain and received later on a distant spin with some
      fidelity. We first obtain simple expressions for the fidelity of quantum state
      transfer and the amount of entanglement sharable between any two sites of an
      arbitrary Heisenberg ferromagnet using our scheme. We then apply this to the
      realizable case of an open ended chain with nearest neighbor interactions. The
      fidelity of quantum state transfer is obtained as an inverse discrete cosine
      transform and as a Bessel function series. We find that in a reasonable time, a
      qubit can be directly transmitted with better than classical fidelity across the
      full length of chains of up to 80 spins. Moreover, our channel allows distillable
      entanglement to be shared over arbitrary distances.

PMID- 14683399
TI  - Effective membrane model of the immunological synapse.
AB  - The immunological synapse is a patterned collection of different types of
      receptors and ligands that forms in the intercellular junction between T cells
      and antigen presenting cells during recognition. The synapse is implicated in
      information transfer between cells, and is characterized by different spatial
      patterns of receptors at different stages in the life cycle of T cells. We obtain
      a minimalist model that captures this experimentally observed phenomenology. A
      functional renormalization group analysis provides further insights.

PMID- 14683400
TI  - Transient activation in a network of coupled map neurons.
AB  - The focus of this Letter is on the activity of a network of neurons pairwise
      coupled by inhibitory connections. Each neuron is represented by a two
      dimensional map capable, when isolated, of a rich variety of complex dynamical
      regimes. It is shown that the network exhibits a stimulus-dependent sequential
      activation and inactivation of subgroups of neurons. This complex behavior is
      rather similar to some spatiotemporal features observed in the first stages of
      the olfaction process in some insects and suggests the possibility of large scale
      simulation of these processes by using reasonable computational capabilities.

PMID- 14683401
TI  - Stochastic resonance driven by time-modulated neurotransmitter random point
      trains.
AB  - Information transmitting by temporally modulated random point trains, such as
      neurotransmitter quanta and spikes, which are neither additive signal and noise
      nor diffusion approximated additive signal and noise, is studied. We demonstrate
      that tuning the input train's average rate can optimize the response of an
      integrate-and-fire model neuron to a signal modulated point train. The
      characteristics of this phenomenon and its biological significance are discussed.

PMID- 14683402
TI  - Spatiotemporal dynamics of damped propagation in excitable cardiac tissue.
AB  - Compared to steadily propagating waves (SPW), damped waves (DW), another solution
      to the nonlinear wave equation, are seldom studied. In cardiac tissue after
      electrical stimulation in an SPW wake, we observe DW with diminished amplitude
      and velocity that either gradually decrease as the DW dies, or exhibit a sharp
      amplitude increase after a delay to become an SPW. The cardiac DW-SPW transition
      is a key link in understanding defibrillation and stimulation close to the
      refractory period, and is ideal for a general study of DW dynamics.

PMID- 14683403
TI  - Multicanonical chain-growth algorithm.
AB  - We present a temperature-independent Monte Carlo method for the determination of
      the density of states of lattice proteins that combines the fast ground-state
      search strategy of the new pruned-enriched Rosenbluth chain-growth method and
      multicanonical reweighting for sampling the complete energy space. Since the
      density of states contains all energetic information of a statistical system, we
      can directly calculate the mean energy, specific heat, Helmholtz free energy, and
      entropy for all temperatures. We apply this method to lattice proteins consisting
      of hydrophobic and polar monomers, and for the examples of sequences considered,
      we identify the transitions between native, globule, and random coil states.
      Since no special properties of heteropolymers are involved in this algorithm, the
      method applies to polymer models as well.

PMID- 14683404
TI  - Principal components of the protein dynamical transition.
AB  - Proteins exhibit a solvent-driven dynamical transition at 180-220 K, manifested
      by nonlinearity in the temperature dependence of the average mean-square
      displacement. Here, molecular dynamics simulations of hydrated myoglobin show
      that the onset of the transition at approximately 180 K is characterized by the
      appearance of a single double-well principal component mode involving a global
      motion of two groups of helices. As the temperature is raised a few more
      quasiharmonic and multiminimum components successively appear. The results
      indicate an underlying simplicity in the protein dynamical transition.

PMID- 14683405
TI  - Manipulation of self-aggregation patterns and waves in a reaction-diffusion
      system by optimal boundary control strategies.
AB  - Reaction-diffusion systems are of considerable importance in many areas of
      physical sciences. For many reasons, an external manipulation of the dynamics of
      these processes is desirable. Here we show numerically how spatiotemporal
      behavior like pattern formation and wave propagation in a two component nonlinear
      reaction-diffusion model of bacterial chemotaxis can be externally controlled. We
      formulate the control goal as an objective functional and apply numerical
      optimization for the solution of the resulting control problem.

PMID- 14683406
TI  - Domain wall tip for manipulation of magnetic particles.
AB  - We demonstrate a method for manipulation of single magnetic microparticles based
      on a domain wall tip displaced in a controlled manner. By applying an external
      magnetic field, the tip can either drag or push magnetic particles. This kind of
      tweezers has potential applications in probing and manipulating colloidal
      systems.

PMID- 14683407
TI  - New scaling of child-langmuir law in the quantum regime.
AB  - This paper presents a consistent quantum mechanical model of Child-Langmuir (CL)
      law, including electron exchange-correlation interaction, electrode's surface
      curvature, and finite emitter area. The classical value of the CL law is
      increased by a larger factor due to the electron tunneling through the space
      charge potential, and the electron exchange-correlation interaction becomes
      important when the applied gap voltage Vg and the gap spacing D are,
      respectively, on the order of Hartree energy level, and nanometer scale. It is
      found that the classical scaling of Vg(3/2) and D(-2) is no longer valid in the
      quantum regime, and a new scaling of Vg(1/2) and D(-4) is established. The smooth
      transition from the classical regime to the quantum regime is also demonstrated.

PMID- 14683408
TI  - Molecular dynamics simulations of a silver atom in water: evidence for a dipolar
      excitonic state.
AB  - The properties of a silver atom in bulk water were studied for the first time by
      molecular dynamics simulations using two complementary mixed quantum-classical
      approaches. The first one consists of treating by quantum mechanics one electron
      only, which interacts with a classical silver cation and solvent through one
      electron pseudopotentials. The second one is Car-Parrinello molecular dynamics
      that treats all the valence electrons quantum-mechanically. Very good agreement
      is obtained between these two methods, and the calculated absorption spectrum of
      the solvated silver atom agrees very well with experimental data. Both
      simulations reveal that the silver atom is in the critical region for the
      appearance of a dipolar excitonic state and exhibits a dipole moment of
      approximately 2 D with large fluctuations of +/-1 D. The structure of the
      solvation shell is also analyzed.

PMID- 14683409
TI  - Comment on "Unusual nature of ferromagnetism coexisting with superconductivity in
      UGe2".

PMID- 14683411
TI  - Comment on "Probabilistic quantum memories".

PMID- 14683413
TI  - Welcome to Pharmacogenomics 2004 - pharmacogenomics comes of age.

PMID- 14683414
TI  - Prospective medicine: the role for genomics in personalized health planning.

PMID- 14683415
TI  - How to understand a complex reality: statistical issues in microarray
      experiments. Interview by Nadine Lemmens.
AB  - Dr Mansmann is Deputy Director of the biostatistic unit of the Institute of
      Medical Biometry and Informatics at the University of Heidelberg Medical School,
      Germany. He is head of the working group in quantitative methods in molecular
      medicine. His research interests are prognostic models for cancer patients and
      establishing methodological standards for reproducible research in molecular
      medicine. As a statistician, he is involved in research on the use of Bayesian
      methodology for complex stochastic systems.

PMID- 14683417
TI  - RNA Interference Technology in Drug Validation and Development: RNomics Approach.

PMID- 14683418
TI  - Pharmacogenomics in Drug Development and Regulatory Decision-making: the Genomic
      Data Submission (GDS) Proposal.

PMID- 14683419
TI  - Pharmacogenomics and breast cancer.
AB  - Germline variants can be used to study breast cancer susceptibility as well as
      the variable response to both drug and radiation therapy used in the treatment of
      breast cancer. In addition to germline high-penetrance mutations important in
      familial and hereditary breast cancer, a substantial component of breast cancer
      risk can be attributed to the combined effect of many low-risk germline
      polymorphisms involved in relevant pathways like those of DNA repair, adhesion,
      carcinogen and estrogen metabolism. Additionally, the identification of sequence
      variants in genes involved in response to chemotherapy and radiation treatment,
      has created the opportunity to apply genomics to individualized treatment. The
      continued insight into the molecular pathways involved in drug and radiation
      response has enabled progress in tailoring therapies in such a way as to both
      maximize efficacy and minimize toxicity. Polymorphisms in genes encoding drug
      metabolizing enzymes, drug transporters and drug targets can be used to predict
      toxicity and response to pharmacologic agents used in breast cancer treatment.
      Similarly, germline variants in genes involved in DNA repair, radiation-induced
      fibrosis and reactive oxygen species may be used to predict response to radiation
      therapy. As a result, pharmacogenomics is rapidly evolving to affect the entire
      spectrum of breast cancer management, influencing both prevention and treatment
      choices.

PMID- 14683420
TI  - Applications of polymorphisms and pharmacogenomics in obstetrics and gynecology.
AB  - The number of reports investigating disease susceptibility based on the carriage
      of low-penetrance, high-frequency polymorphisms has steadily increased over the
      last years. Evidence based on meta-analyses of individual case-control studies is
      accumulating, defining specific individual variations in disease susceptibility.
      For example, genetic variations of the estradiol metabolism have been described
      as significant contributors to disease susceptibility with variations depending
      on ethnic background. In the field of obstetrics and gynecology, the genetic
      contribution of polymorphic markers to a series of disorders has been
      characterized. These disorders include recurrent pregnancy loss, pre-eclampsia,
      endometriosis, breast cancer, and hormone replacement therapy (HRT)-related
      complications such as thrombosis. Among other genetic markers, thrombophilic
      genetic variants, such as the Factor V Leiden and prothrombin G20210A
      polymorphisms, as well as genetic variants of cytochrome P450 (CYP) enzymes, for
      example, CYP19 and CYP1B1, have been established as genetic risk markers and
      disease modifiers of recurrent and sporadic pregnancy loss and HRT-independent
      and -dependent breast cancer, respectively. In addition, meta-analyses of data in
      the literature established the TGFBR1*6A, GSTP I105V, and TP53 R72P
      polymorphisms, as well as the GSTM1 gene deletion as low-penetrance genetic risk
      factors of sporadic breast cancer. With respect to genetic modulation of
      therapeutic effects, beneficial effects of estrogen replacement therapy and HRT
      are modulated by the carriage of single nucleotide polymorphisms, for example,
      osteoprotection and blood lipid changes by the estrogen receptor-alpha (ER-a)
      PvuII polymorphism. Polymorphisms of the catechol-O-methyltransferase (COMT), ER
      alpha, IL-1 receptor antagonist, and Factor V genes have been demonstrated to
      modulate the timing of natural menopause. Lastly, a strong genetic contribution
      of polymorphisms to the development and the clinical course of endometriosis has
      been established with data pointing to polymorphisms of the COMT, GST, NAT-2, and
      ER-alpha genes as susceptibility markers. In summary, the available evidence
      points to a number of polymorphisms of a wide variety of genes as strong
      hereditary determinants of the susceptibility to benign and malignant gynecologic
      and obstetric conditions.

PMID- 14683421
TI  - The genetic polymorphism of drug transporters: functional analysis approaches.
AB  - Evidence is accumulating to strongly suggest that drug transporters are one of
      the determining factors governing the pharmacokinetic profile of drugs. To date,
      a variety of drug transporters have been cloned and classified as solute carriers
      and ATP-binding cassette transporters. Such drug transporters are expressed in
      various tissues such as the intestine, brain, liver, and kidney, and play
      critical roles in the absorption, distribution and excretion of drugs. However,
      at the present time, information is limited regarding the genetic polymorphism of
      drug transporters and its impact on their function. In this context, we have
      undertaken the functional analyses of the polymorphisms identified in drug
      transporter genes. This article aims to provide an overview on the functional
      aspects of the non-synonymous polymorphisms of drug transporters and to present
      standard methods for the evaluation of the effect of polymorphisms on their
      function.

PMID- 14683422
TI  - Identification of antimicrobial targets using a comprehensive genomic approach.
AB  - Regulated antisense RNA enables the construction of a defined set of conditional
      growth-defective/lethal strains. In this study, we expanded the regulated
      antisense RNA interference technology and developed a high-throughput screening
      strategy to identify the potential drug targets of novel antimicrobials. To prove
      this concept, the specific antisense sublibrary of different essential open
      reading frames were pooled in the presence of an inducer, and treated with or
      without sublethal levels of mupirocin, triclosan, or gentamicin. Antisense RNA
      expressing strains that were sensitized for increased susceptibility to the
      antibiotics were selectively detected via DNA subtractive hybridization,
      microarray, and whole-cell analyses. No strain was identified as supersensitive
      to gentamicin because there was no target-specific antisense strain in this
      sublibrary. In contrast, strains expressing antisense to isoleucine tRNA
      synthetase (ileS) and enoyl-[acyl-carrier-protein] reductase (fabI) were
      specifically identified as having increased susceptibility to mupirocin and
      triclosan, respectively. These results demonstrated that ileS and fabI antisense
      strains showed significant increases of susceptibility only to their specific
      inhibitors. This data demonstrates that a regulated antisense RNA expression
      library provides an effective tool to assist in the identification of potential
      targets for novel antibacterial agents.

PMID- 14683423
TI  - Genetic variability and evolution of two pharmacologically important classes of
      genes.
AB  - We have studied the human genetic variability of single nucleotide polymorphisms
      (SNPs) and haplotypes in two pharmaceutically important classes of genes that
      might be expected to experience different evolutionary pressures: antigen
      presentation and processing (APP) and nuclear hormone receptor (NHR) genes. We
      compared the variation pattern in these two classes of genes with 5119 reference
      (REF) genes. We assessed this variability by sequencing and discovering SNPs in
      5'-upstream, 5'-untranslated region (5'UTR), exon, intron, 3'UTR and 3'
      downstream regions of all these genes in 79 unrelated humans from diverse ethnic
      backgrounds, one chimpanzee (Pan troglodytes) and a gorilla (Gorilla gorilla).
      SNP density and nucleotide diversity were higher in the APP genes than the REF
      genes. Relative to the REF genes, APP SNP density was significantly higher in the
      coding and 3'UTR regions. Higher variation in the coding region of the APP genes
      was due specifically to having more non-synonymous changes, which suggests that
      natural selection may be acting to promote change or diversity in these proteins.
      In contrast, the NHR genes showed lower SNP density and diversity relative to REF
      genes. The NHR genes consistently showed lower nucleotide diversity in all the
      genomic regions except in the 3'downstream region. SNP frequency data on the non
      synonymous SNPs also suggested that the coding region in the NHR genes is
      conserved to a higher degree than the coding region in the REF genes.
      Significantly lower SNP density was observed in the 5'-upstream and 5'UTR regions
      of the NHR genes, perhaps reflecting selective conservation of these regions.
      Heterozygosity in the APP genes was significantly higher than in the NHR genes in
      each of the three species tested. Moreover, between species there were more fixed
      differences in the APP genes than in the NHR genes. Substantial variability
      exists in these two classes of genes. It is important to consider this
      interindividual variability pattern while developing drugs that act on such
      targets.

PMID- 14683424
TI  - Digene Corporation.
AB  - Digene Corporation is a molecular diagnostics company that develops, manufactures
      and markets proprietary gene-based testing systems for the screening, monitoring
      and diagnosis of human diseases. The company's primary focus is in women's
      cancers and infectious diseases. Our proprietary, patented Hybrid Capture((R))
      technology has been successfully applied to the development of diagnostic tests
      for human papillomavirus (HPV), Chlamydia, Gonorrhea, hepatitis B virus and
      cytomegalovirus. Digene's Hybrid Capture 2 (hc2) trade mark HPV DNA test has now
      been established as part of the standard of care for cervical cancer screening in
      the US. We are focusing our research and development activities on support and
      improvement of existing product lines as well as the development of several new
      products. We have several ongoing basic research programs with the goal of
      developing improved molecular diagnostic assay systems for the detection of HPV
      and other targets of interest in the area of women's cancers and infectious
      diseases. Digene's goal is to establish primary screening by the Hybrid Capture
      HPV DNA Test as the worldwide standard of care for cervical cancer screening.

PMID- 14683425
TI  - Molecular genetics of Porphyromonas gingivalis: gingipains and other virulence
      factors.
AB  - Porphyromonas gingivalis is a black-pigmented anaerobic gram-negative bacterium
      that is a major pathogen of chronic adult periodontitis, an inflammatory disease
      of tooth-supporting tissues. P. gingivalis possesses a number of potential
      virulence factors. Among them, cell-surface-associated and secreted proteinases
      such as Arg-gingipain and Lys-gingipain have received much attention because they
      can degrade various host proteins and cause inflammation. Molecular genetic
      analysis is extremely powerful to evaluate the significance of each virulence
      factor in a pathogenic microorganism. This review will describe the introduction
      of molecular genetics to analysis of pathogenesis of P. gingivalis and the
      findings that have been obtained using knockout mutants of various potential
      virulence factors, especially proteinases.

PMID- 14683426
TI  - Gingipains, the major cysteine proteinases and virulence factors of Porphyromonas
      gingivalis: structure, function and assembly of multidomain protein complexes.
AB  - Gingipains, extracellular cysteine proteinases of Porphyromonas gingivalis,
      constitute the major virulence factor of this periodontopathogenic bacterium.
      They are the product of three genes, two coding for an Arg-specific (RgpA and
      RgpB) and one for a Lys-specific proteinase (Kgp). Proteinase domains of RgpA and
      RgpB are virtually identical; however, the gene encoding the former enzyme is
      missing a large segment coding for hemaglutinin / adhesin (HA) domains. The
      latter domains are present also in Kgp. The tertiary structure of RgpB revealed
      that the proteinase domain of gingipains has a protein fold referred to as the
      caspase-hemoglobinase fold. On this basis, they are also evolutionary related to
      other highly specific proteinases including clostripain, caspases, legumains and
      separase (clan CD of cysteine peptidases). Gingipains are produced as large
      preproproteins and are subject to elaborate, not yet fully understood, secretion,
      glycosylation, activation, and maturation processes. How they traverse the outer
      membrane is unknown, although it can be hypothesized that they use an
      autotransporter pathway. Apparently during transport through the periplasm the
      LPS-like glycan moiety is added at the conserved C-terminal portion of
      progingipains. At the cell surface pro-gingipains fold into partially active,
      single-chain zymogens and undergo autocatalytic, intermolecular processing. Two
      sequential cleavages within the profragment domain enhance zymogen activity and
      in the case of RgpA and Kgp are followed by excision of the individual HA
      domains. These domains are further truncated at the C-terminus by concerted
      action of Kgp and carboxypeptidase and form a non-covalent multidomain,
      multifunctional complex anchored into the outer membrane by the glycated, C
      terminal HA domain. This hypothetical scenario is a reasonable explanation for
      the occurrence of many forms of gingipains.

PMID- 14683427
TI  - Porphyromonas gingivalis gingipains: the molecular teeth of a microbial vampire.
AB  - The gingipains are cell surface Arg- and Lys-specific proteinases of the
      bacterium Porphyromons gingivalis, which has been associated with periodontitis,
      a disease that results in the destruction of the teeth-s supporting tissues. The
      proteinases are encoded by three genes designated rgpA, rgpB and kgp. Arg
      specific proteolytic activity is encoded by rgpA/B and the Lys-specific activity
      by kgp. RgpA and Kgp are polyproteins comprising proteinases with C-terminal
      adhesin domains that are proteolytically processed. After processing, the domains
      remain non-covalently associated as complexes on the cell surface. RgpB is also a
      cell surface proteinase but does not associate with adhesin domains. Using gene
      knockout P. gingivalis mutants, the proteolytic processing of the gingipain
      domains has been shown to involve the gingipains themselves as well as C-terminal
      processing by a carboxypeptidase. A motif in the C-terminal domain of each
      protein/polyprotein has been identified that is suggested to be involved in
      attachment to LPS on the cell surface. RgpB lacks a C-terminal adhesin binding
      motif found in the catalytic domains of RgpA and Kgp. This adhesin binding motif
      is proposed to be responsible for the non-covalent association of the RgpA and
      Kgp catalytic domains into the cell surface complexes with the processed adhesin
      domains. The RgpA-Kgp proteinase-adhesin complexes, through the adhesin domains
      A1 and A3, have been implicated in colonization of P. gingivalis by binding to
      other bacteria in subgingival plaque and also binding to crevicular epithelial
      cells. The RgpA-Kgp complexes also bind to fibrinogen, laminin, collagen type V,
      fibronectin and hemoglobin. Amino acid sequences likely to be involved in binding
      to these host proteins have been identified in adhesin domains A1 and A3. It is
      proposed that these adhesins target the proteolytic activity to host cell surface
      matrix proteins and receptors. The continual cycle of binding and degradation of
      the surface proteins/receptors on epithelial, fibroblast and endothelial cells by
      the RgpA-Kgp complexes in the gingival tissue leading to cell death would
      contribute to inflammation, tissue destruction and vascular disruption
      (bleeding). P. gingivalis has an obligate growth requirement for iron and
      protoporphyrin IX, which it preferentially utilizes in the form of hemoglobin.
      Kgp proteolytic activity is essential for rapid hydrolysis of hemoglobin and it
      is suggested therefore that a major role of the RgpA-Kgp complexes is in vascular
      disruption and the binding and rapid degradation of hemoglobin for heme
      assimilation by P. gingivalis. The RgpA-Kgp complexes also have a major role in
      the evasion and dysregulation of the host-s immune response. It is proposed that
      host pro-inflammatory cytokines and cellular receptors close to the infection
      site may be rapidly and efficiently degraded by the gingipains while the
      proteinases at lower concentrations distally could result in the promotion of an
      inflammatory response through activation of proteinase-activated receptors and
      cytokine release. The culmination of this dysregulation would be tissue
      destruction and bone resorption. In animal models of disease the RgpA-Kgp complex
      when used as a vaccine to produce a high titre antibody response protects against
      challenge with P. gingivalis. Using recombinant domains of RgpA and Kgp as
      vaccines, it has been demonstrated that the A1 and A3 domains confer protection.

PMID- 14683428
TI  - Glycosylation of the Arg-gingipains of Porphyromonas gingivalis and comparison
      with glycoconjugate structure and synthesis in other bacteria.
AB  - Post-translational modification of proteins by covalent attachment of sugars to
      the protein backbone (protein glycosylation) is the most common post
      translational modification in the eucaryotic cell. However, the addition of
      carbohydrates to proteins of Eubacteria and Archaea has been demonstrated and
      accepted only recently. There is now a rapidly expanding list of bacterial
      glycoproteins that have been characterised from a variety of different organisms
      including many important pathogens. The Arg-gingipains of Porphyromonas
      gingivalis are recent additions to this list. In this review we present a summary
      of our investigations on the structure of the glycan additions to these
      proteolytic enzymes, the genetics of the glycosylation process and some of the
      effects on enzyme function and recognition. These findings are placed in the
      context of the current status of understanding of glycoconjugate structure and
      synthesis in other bacteria. Given the importance of glycosylation of eucaryotic
      proteins to their stability, structure, resistance to proteolysis and
      recognition, the modifications to the proteases described in the present report
      are likely to have a functional role in the properties of these enzymes in
      periodontal disease.

PMID- 14683429
TI  - The biphasic virulence activities of gingipains: activation and inactivation of
      host proteins.
AB  - Gingipains are trypsin-like cysteine proteinases produced by Porphyromonas
      gingivalis, a major causative bacterium of adult periodontitis. Rgps (HRgpA and
      RgpB) and Kgp are specific for -Arg-Xaa- and -Lys-Xaa- peptide bonds,
      respectively. HRgpA and Kgp are non-covalent complexes containing separate
      catalytic and adhesion/hemagglutinin domains, while RgpB has only a catalytic
      domain with a primary structure essentially identical to that of the cata-lytic
      subunit of HRgpA. The multiple virulence activities of gingipains are reviewed in
      view of the biphasic mechanisms: activation and inactivation of host proteins.
      Rgps enhanced vascular permeability through prekallikrein activation or direct
      bradykinin release in combination with Kgp. This Rgp action is potentially
      associated with gingival edema and crevicular fluid production. Rgps activate the
      blood coagulation system, leading to progression of inflammation and consequent
      alveolar bone loss in the periodontitis site. Rgps also activate protease
      activated receptors and induce platelet aggregation, which, together with the
      coagulation-inducing activity, may explain an emerging link between periodontitis
      and cardiovascular disease. Kgp is the most potent fibrinogen/fibrin degrading
      enzyme of the three gingipains in human plasma, being involved in the bleeding
      tendency at the diseased gingiva. Gingipains stimulate expression of matrix
      metalloproteinases (MMPs) in fibroblasts and activate secreted latent MMPs that
      can destroy periodontal tissues. Gingipains degrade cytokines, components of the
      complement system and several receptors, including macrophage CD14, T cell CD4
      and CD8, thus perturbing the host-defense systems and thereby facilitating
      sustained colonization of P. gingivalis. Gingipains are potent virulence factors
      of P. gingivalis, and in many regards their pathogenic activities constitute new
      mechanisms of bacterial virulence.

PMID- 14683430
TI  - Suppression of virulence of Porphyromonas gingivalis by potent inhibitors
      specific for gingipains.
AB  - Porphyromonas gingivalis is a Gram-negative anaerobic bacterium that is
      implicated as a major etiologic agent of adult periodontal disease. This
      bacterium is asaccharolytic and possesses strong potency for proteolysis. It
      produces a novel class of cysteine proteinases, termed gingipains, in the cell
      associated and secretory forms. Gingipains consist of arginine-X-specific
      cysteine proteinases (Arg-gingipains, Rgps) and lysine-X-specific cysteine
      proteinase (Lys-gingipain, Kgp). Previous studies using various P. gingivalis
      mutants deficient in Rgp- and/or Kgp-encoding genes have revealed that both
      enzymes are important for the bacterium both to exhibit its virulence and to
      survive in periodontal pockets. Mammalian internal proteinase inhibitors such as
      cystatins, a1-antichymotrypsin, and tissue inhibitor of metalloproteinases
      (TIMPs) have little or no effects on the proteolytic activities of these enzymes,
      suggesting the evasion of the bacterium from host defense mechanisms. Recent
      epidemiological reports have shown a significant relation between periodontal
      diseases and systemic diseases such as cardiovascular diseases and diabetes.
      Thus, the development of potent inhibitors specific for gingipains provides new
      therapeutic approaches to treat periodontal diseases and the related systemic
      diseases. More recently, we have developed novel synthetic inhibitors specific
      for Rgp and Kgp, based on the specificity and efficacy of cleavage of histatins
      by each enzyme. We have also isolated a novel and potent inhibitor of Rgp from
      the culture supernatant of Streptomyces species strain FA-70, now designated as
      FA-70C1. Here we summarized the usefulness of these new inhibitors in providing a
      broader application in studies of this important class of enzymes.

PMID- 14683431
TI  - Human inter-individual DNA sequence variation in candidate genes, drug targets,
      the importance of haplotypes and pharmacogenomics.
AB  - The identification of genes predisposing to human diseases is of paramount
      importance for understanding the molecular basis of the disease and individually
      different drug response, and will establish new routes to diagnosis and
      therapeutic advances of immense medical benefit. A key step common to all
      strategies for disease gene identification is the systematic analysis of
      candidate gene sequences to identify specific sequence variations associated with
      disease or any other phenotype of pharmaceutical relevance. In this article,
      current concepts and approaches to haplotype-based candidate gene analysis are
      reviewed. Moreover, a comprehensive summary of recent studies and data on the
      amount, nature, pattern and structure of genetic variation in candidate genes is
      given. These data demonstrate altogether remarkable gene sequence and haplotype
      diversity. Numerous individually different forms of a gene may exist. This
      presents challenges to the traditional views of the concept of "a" gene with far
      reaching implications on the functional analysis of candidate gene variation, on
      the establishment of "sequence"-"structure"-"function" and complex
      haplotype/genotype-phenotype relationships, on the identification, evaluation and
      prioritization of drug targets and the concept of a "personalized medicine" in
      general. Moreover, present and future approaches to the identification of
      candidate and disease genes will be addressed. These include whole genome-based
      approaches such as integrative genomics as well as functional genomics-based
      approaches to analyze and model complex biological and medical processes. The
      analysis of whole complex systems in particular will provide the basis to make
      "maximally informed" guesses on candidate genes and address complex variability
      patterns in genes as well as complex genotype-phenotype relationships
      comprehensively at an advanced level.

PMID- 14683432
TI  - Arrays of immobilized oligonucleotides--contributions to nucleic acids
      technology.
AB  - The interactions of nucleic acids technology and the technology of arrayed
      nucleic acids are described, showing the interdependence of nucleic acids
      chemistry, surface chemistry, (micro-) technology and the requirements of bio
      medical applications. The methods and problems of the production of large numbers
      of oligonucleotides as well as the methods of arraying oligonucleotides are
      highlighted. The basic approaches, in-situ synthesis and postsynthetic
      immobilization, are described with a special emphasis on the postsynthetic
      immobilization of ready-made oligonucleotides on support materials. Techniques
      for the detection of nucleic acids interactions on arrays are outlined in brief.

PMID- 14683433
TI  - The making of a portrait--bringing it into focus.
AB  - The data generated by DNA arrays are often described as the molecular "portrait"
      of a particular physiological/pathological sample. Although the emotional
      reactions could range from revulsion to adoration when viewing those portraits,
      as it might be when viewing some contemporary art, array technology has
      fundamentally changed the way researchers approach many biomedical questions.
      With its ability to monitor the expression level of tens of thousands genes
      simultaneously, microarray technology has been able to identify "markers" for
      complex diseases such as cancer. While massive amounts of work lie ahead to
      validate those marker genes, many researchers are turning their attentions to the
      low-density, focused arrays. When incorporated with current knowledge on specific
      biological pathways, these specially tailored macroarrays may be better fitted
      for purposes such as diagnosis, drug discovery and validation, and prognostic
      assessment of clinical treatments.

PMID- 14683434
TI  - Virus diagnostics on microarrays.
AB  - Whereas the majority of microarray applications still deal with expression
      analysis for gathering information about levels of gene products at certain cell
      states, other approaches simply ask the question whether particular genes, which
      are usually indicative for particular microorganisms and pathogens, are present
      in a sample or not. Investigations that are more detailed try to evaluate the
      presence of particular subtypes of a given pathogen. The combination of
      microarray technology and virus diagnostics promises to generate an ideal
      platform for fast, sensitive, specific, and parallelized virus diagnostics.
      Performing virus diagnostics on microarrays, however, requires other basic
      techniques to be optimized. This is necessary in order to obtain unambiguous and
      reproducible results, which are compatible with the needs for clinical routine.
      Parameters that have to be considered include supports, coupling chemistry,
      chemical oligonucleotide synthesis, signal enhancement strategies, and optimal
      coordination of PCR reactions, hybridizations, and signal detection, as well as
      interpretation strategies. Finally, considerations should be given to economic
      aspects, one chip-one patient strategies and low integrated arrays as a custom
      tailored way to fast and accurate diagnostic tools.

PMID- 14683435
TI  - Software packages for quantitative microarray-based gene expression analysis.
AB  - Microarray technology enables researchers to investigate the expression of
      several thousand genes simultaneously. The whole transcriptional response of
      these genes in normal cells or tissue, in disease condition, as an response to
      biological, genetical or chemical stimuli or during normal biological processes
      such as cell cycle or embryonic development can be investigated. This leads to a
      huge amount of data, from which the relevant information has to be extracted by
      statistical and computational methods. Several software packages for the analysis
      of gene expression data are available, both commercially and freely. They differ
      particularly with regard to the implemented analytical methods, the graphical
      display and the manageability. In this paper the commercial software packages
      arraySCOUT, GeneSpring and Spotfire DecisionSite for Functional Genomics are
      compared and their applicability for analysis of gene expression data is studied.
      Small artificial and application test datasets are used to compare the
      computational results of the software packages. As far as possible results are
      verified with standard statistical software package SAS.

PMID- 14683436
TI  - Advances in encoding of colloids for combinatorial libraries: applications in
      genomics, proteomics and drug discovery.
AB  - The creation of enormous libraries of chemicals and their subsequent screening
      for bioactivity has been accelerated through recent developments in encoding
      solid supports. The ability to accurately identify the structure of a biomolecule
      that has exhibited activity is invaluable and is closer to realisation in the
      advent of smart nanoscience. In this review the evolution of encoding solid
      supports as platforms for combinatorial synthesis is traced. Current approaches
      to encoding solid supports are reviewed and their potential for use as supports
      for the high-throughput screening of split and mix libraries explored. Finally, a
      brief consideration of the status of the application of encoded libraries is
      provided including creative chemical and colloidal encoding.

PMID- 14683437
TI  - Data reduction methods for application of fluorescence correlation spectroscopy
      to pharmaceutical drug discovery.
AB  - Fluorescence methods are commonly used in pharmaceutical drug discovery to assay
      the binding of drug-like compounds to signaling proteins and other bio-particles.
      For binding studies of non-fluorescent compounds, a competitive format may be
      used in which the binding of the compound results in displacement of another
      fluorescently labeled ligand. Highly-sensitive measurements within nano-liter
      sized open probe volumes can be accomplished using a confocal epi-illumination
      geometry and thus key tools for such drug-binding studies include fluorescence
      correlation spectroscopy (FCS) and its related techniques. This paper reviews the
      general protocol for application of FCS to biomolecular compound-binding assays
      and it focuses on methods for the reduction of experimental photon count data to
      obtain the normalized autocorrelation function (ACF), on theoretical models of
      the ACF, and on statistical and systematic errors in the experimental ACF.
      Results from a detailed Monte Carlo simulation of FCS, which are useful for
      testing theoretical models and validating short-duration assay capabilities, are
      discussed. An illustrative example is presented on the use of FCS to assay
      binding of Alexa-488-labeled Bak peptide with Bcl-x(L), which is an intracellular
      protein that acts to protect against programmed cell death.

PMID- 14683438
TI  - New fluorescence techniques for high-throughput drug discovery.
AB  - The rapid increase of compound libraries as well as new targets emerging from the
      Human Genome Project require constant progress in pharmaceutical research. An
      important tool is High-Throughput Screening (HTS), which has evolved as an
      indispensable instrument in the pre-clinical target-to-IND (Investigational New
      Drug) discovery process. HTS requires machinery, which is able to test more than
      100,000 potential drug candidates per day with respect to a specific biological
      activity. This calls for certain experimental demands especially with respect to
      sensitivity, speed, and statistical accuracy, which are fulfilled by using
      fluorescence technology instrumentation. In particular the recently developed
      family of fluorescence techniques, FIDA (Fluorescence Intensity Distribution
      Analysis), which is based on confocal single-molecule detection, has opened up a
      new field of HTS applications. This report describes the application of these new
      techniques as well as of common fluorescence techniques--such as confocal
      fluorescence lifetime and anisotropy--to HTS. It gives experimental examples and
      presents advantages and disadvantages of each method. In addition the most common
      artifacts (auto-fluorescence or quenching by the drug candidates) emerging from
      the fluorescence detection techniques are highlighted and correction methods for
      confocal fluorescence read-outs are presented, which are able to circumvent this
      deficiency.

PMID- 14683439
TI  - High fidelity SNP genotyping using sequence-specific primer elongation and
      fluorescence correlation spectroscopy.
AB  - Reliable, efficient and cost-effective modalities are urgently needed for mass
      screening of gene mutations. Previous reports have shown that SSCP or genechip
      methods require substantial time and monetary costs, thus limiting their appeal.
      Sequence Specific Primer Polymerase Chain Reaction (SSP-PCR) is a reliable and
      cost-effective method that utilizes the 3'-end discrimination properties of
      polymerase. However, the applicability of conventional SSP-PCR is limited due to
      the difficulties associated with determining optimal conditions and because mis
      matched primers are amplified, resulting in signal noise during end-point assay.
      To overcome this problem, we eliminated the reverse primers from SSP-PCR, thus
      preventing amplification of mis-matched primers. We designated this method
      Sequence-Specific Primer Cycle Elongation (SSPCE). However, the detection of
      elongated sequence specific primers was difficult using conventional
      electrophoresis due to the small amounts of amplification product present. We
      therefore combined SSPCE and Fluorescence Correlation Spectroscopy, which is a
      novel technique used to determine the number and size of fluorophores at nano
      molar concentrations, and designated the method SSPCE-FCS. We compared
      conventional SSP-PCR and SSPCE-FCS with regard to determining optimal conditions
      using two Mitochondrial SNPs (G --> A at position 1598, G --> A at position
      12192). We were able to determine the optimal conditions for the SNP at position
      1598 using either method. However, optimal conditions could only be determined
      for SSPCE-FCS with the 12192 mutation because non-specific amplification was
      observed at a wide range of annealing temperatures in SSP-PCR. We then applied
      this method to three other SNPs and the results were consistent with the results
      of sequencing data.

PMID- 14683447
TI  - A short course on virology / vectorology / gene therapy.
AB  - For people starting off in the field of gene therapy, the encountered terminology
      is often quite confusing. Moreover, the background on basic virology may be
      modest. The following introduction provides a head start to any novice willing to
      gain more in-depth knowledge on the subject. The development of gene therapy is
      also addressed from a historical perspective.

PMID- 14683448
TI  - Biosafety of lentiviral vectors.
AB  - The characteristics of lentiviral vectors (stable integration in non-dividing and
      dividing cells, long-term expression of the transgene, absence of immune
      response) make them ideal gene transfer vehicula for future gene therapy.
      However, the most potent lentiviral vectors are derived from highly pathogenic
      human viruses, such as HIV. We describe how the field has engineered lentivectors
      with increasing biosafety both for the lab worker and for the patient. The risk
      associated with state-of-the-art lentivectors is therefore minimal, although a
      psychological barrier to use these vectors in the clinic may still have to be
      overcome. Due to their increased performance, care should be taken to avoid
      accidental transduction of the lab worker with potential hazardous genes. The
      precautions which have to be taken are described in detail.

PMID- 14683449
TI  - Biosafety of onco-retroviral vectors.
AB  - Extensive gene therapy studies in preclinical models and in clinical trials
      underscore the relative safety of onco-retroviral vectors. Up until recently, no
      adverse effects have been reported in nearly 2000 patients that were enrolled in
      gene therapy clinical trials involving onco-retroviral vectors. However, the main
      safety concern of using onco-retroviral vectors is related to the risk of
      malignant transformation following oncogene activation due to random onco
      retroviral genomic integration. Based on primate studies, there is an apparent
      low risk of malignancy that is predominately associated with the occurrence of
      chronic retroviremia resulting from replication-competent retroviruses (RCR),
      particularly in immunosuppressed recipient hosts. However, in the latest
      packaging cell lines and vectors, the risk of RCR-generation has been drastically
      reduced, primarily by minimizing the homologous overlap between vector and helper
      sequences. Nevertheless, results from a recent preclinical study in mice and a
      clinical trial in patients suffering from SCID-X1 strongly suggest that onco
      retroviral vectors devoid of RCR can contribute to lymphomagenesis by insertional
      activation of cellular oncogenes. The risk of inadvertent germline transmission
      of onco-retroviral vectors appears to be low, especially relative to the
      endogenous rate of germline insertion, which is known to occur naturally in the
      human population via transmission of endogenous retro-transposons. The strict
      dependency of onco-retroviral gene transfer on cell division is an important
      safety advantage that significantly limits the risks of horizontal transmission.
      Since improved onco-retroviral vectors or transduction protocols may result in an
      increased number of retroviral integrations per cell, this may concomitantly
      increase the risk of malignant transformation. The use of suicide genes, self
      inactivating vectors and/or chromosomal insulators is, therefore, warranted to
      further enhance the safety features of onco-retroviral vectors. Detailed analyses
      of insertion sites combined with long-term clinical follow-up may contribute to a
      more accurate risk assessment.

PMID- 14683450
TI  - Biosafety of adenoviral vectors.
AB  - Adenoviral vectors can efficiently transduce a broad variety of different cell
      types and have been used extensively in preclinical and clinical studies.
      However, early generation of adenoviral vectors retained residual adenoviral
      genes that contribute to inflammatory immune responses and toxicity. In addition,
      these vectors often result in transient expression of the potentially therapeutic
      transgene. Some clinical trials based on early generation adenoviral vectors have
      been discontinued because of acute inflammatory responses and toxicity and even
      one patient has died as a direct consequence of adenoviral toxicity. The latest
      generation of high-capacity adenoviral vectors is devoid of viral genes, and is
      having a significantly improved safety profile and yielding more prolonged
      transgene expression compared to early generation vectors. Nevertheless,
      transgene expression gradually declines even when high-capacity adenoviral
      vectors are used, possibly due to the gradual loss of vector genomes. Despite
      their improved safety, high-capacity adenoviral vectors can still trigger
      transient toxic effects in animals and patients. Restricting the tropism of
      adenoviral vectors by immunologic or genetic re-targeting may further improve
      their therapeutic window. The safety of adenoviral vectors has been improved
      further through the development of safer packaging systems that eliminate the
      homologous overlap between vector and helper sequences and therefore prevent
      formation of replication-competent adenoviruses (RCA). RCA could exacerbate
      inflammatory responses and act as a helper to rescue adenoviral vectors,
      potentially increasing the effective vector dose. Conditionally replicating
      adenoviruses (CRAds) have been developed for cancer gene therapy, which replicate
      selectively in some cancer cells. The use of CRAds in combination with
      chemotherapy yielded therapeutic effects in patients suffering from cancer but
      dose-limiting toxicity was apparent. Although there appears to be a very low
      theoretical risk of malignancy that is predominantly associated with the
      occurrence of E1-positive recombinants, no malignancies have been reported that
      were associated with adenoviral vectors. Nevertheless, integrating adenoviral
      vectors carry a greater malignancy risk due to their ability to integrate
      randomly into the target genomes.

PMID- 14683451
TI  - Evaluation of risks related to the use of adeno-associated virus-based vectors.
AB  - Recombinant AAV efficacy has been demonstrated in numerous gene therapy
      preclinical studies. As this vector is increasingly applied to human clinical
      trials, it is a priority to evaluate the risks of its use for workers involved in
      research and clinical trials as well as for the patients and their descendants.
      At high multiplicity of infection, wild-type AAV integrates into human chromosome
      19 in approximately 60% of latently infected cell lines. However, it has been
      recently demonstrated that only approximately 1 out of 1000 infectious units can
      integrate. The mechanism of this site-specific integration involves AAV Rep
      proteins which are absent in vectors. Accordingly, recombinant AAV (rAAV) do not
      integrate site-specifically. Random integration of vector sequences has been
      demonstrated in established cell lines but only in some cases and at low
      frequency in primary cultures and in vivo. In contrast, episomal concatemers
      predominate.Therefore, the risks of insertional mutagenesis and activation of
      oncogenes are considered low. Biodistribution studies in non-human primates after
      intramuscular, intrabronchial, hepatic artery and subretinal administration
      showed low and transient levels of vector DNA in body fluids and distal organs.
      Analysis of patients body fluids revealed rAAV sequences in urine, saliva and
      serum at short-term. Transient shedding into the semen has been observed after
      delivery to the hepatic artery. However, motile germ cells seemed refractory to
      rAAV infection even when directly exposed to the viral particles, suggesting that
      the risk of insertion of new genetic material into the germ line is absent or
      extremely low. Risks related to viral capsid-induced inflammation also seem to be
      absent since immune response is restricted to generation of antibodies. In
      contrast, transgene products can elicit both cellular and humoral immune
      responses, depending on the nature of the expressed protein and of the route of
      vector administration. Finally, a correlation between early abortion as well as
      male infertility and the presence of wt AAV DNA in the genital tract has been
      suggested. Although no causal relationship has been established, this issue
      stresses the importance of using rAAV stocks devoid of contaminating replication
      competent AAV. This review comprehensively examines virus integration,
      biodistribution, immune interactions, and other safety concerns regarding the
      wild-type AAV and recombinant AAV vectors.

PMID- 14683452
TI  - Risk assessment of the use of autonomous parvovirus-based vectors.
AB  - Autonomous parvoviruses are small, non-enveloped, lytic DNA viruses replicating
      in the nucleus of actively dividing mammalian cells of appropriate species and
      tissue origins. In contrast to AAV, the other main subgroup of parvoviruses,
      autonomous parvoviruses do not require the assistance of an auxiliary virus for
      productive infection and do not stably integrate in the cellular DNA. Therefore,
      autonomous parvoviruses are suitable vectors for mediating transient gene
      transduction in dividing target cells. Interestingly, some of these viruses
      possess a striking inherent oncotropism, which may render them particularly
      suitable as selective vehicles in the clinical context of cancer gene therapy. In
      this chapter, we will present a brief overview of the biology of autonomous
      parvoviruses. This topic will be followed by a description of the design and
      recent developments in the production and use of parvoviral vectors, with a
      particular emphasis on biosafety aspects. Finally, the risk assessment related to
      the production and use of parvoviral vectors will be discussed in last part of
      the chapter.

PMID- 14683453
TI  - The uses of poxviruses as vectors.
AB  - Poxviruses have played an amazing role in the development of virology, immunology
      and vaccinology. In 1796, deliberate inoculation of cowpox virus to humans was
      proved by Dr. Edward Jenner to protect against the antigenically related smallpox
      virus (variola). This discovery founded the science of immunology and eventually
      led to smallpox eradication from the earth in 1980 after a world wide vaccination
      campaign with vaccinia virus (another poxvirus). Paradoxically, despite the
      eradication of smallpox, there has been an explosion of interest in vaccinia
      virus in the eighties. This interest has stemmed in part from the application of
      molecular genetics to clone and express foreign genes from recombinant vaccinia
      virus. The use of these recombinant vaccinia viruses as efficacious in vitro
      expression system and live vaccine has raised concerns about their safety. The
      work of the scientific community of the last 20 years has contributed to improve
      drastically the safety of poxvirus derived vectors. Firstly, the safety of
      vaccinia virus has been enhanced by production of genetically attenuated strains.
      Secondly, alternative poxvirus vectors, such as avipoxviruses, were proved to be
      extremely safe and efficacious non-replicating vectors when used in non avian
      species. In the present chapter, the basic concepts of poxvirus biology required
      to assess the safety of a poxvirus derived vector are provided. The principal
      poxvirus vectors available to date are described in regards to their biosafety.

PMID- 14683454
TI  - Biosafety of herpesvirus vectors.
AB  - Herpesviruses are large DNA viruses, which possess a number of advantages as gene
      delivery vectors. These relate to an ability to package large DNA insertions and
      establish lifelong latent infections in which the viral genome exists as a stable
      episome in the nucleus. For gene therapy to become a potential future treatment
      option, biosafe therapeutically efficient gene transfer is a central, but more
      and more stringent requirement. This review highlights the progress in
      development of herpesvirus based vectors, describes their properties as wall as
      discusses the biosafety concerns that are associated with their use in gene
      therapy. Thought was also given to biosafety issues pertaining to design and
      production of herpesvirus vector systems in therapeutic gene delivery.

PMID- 14683455
TI  - Dual roles of adiponectin/Acrp30 in vivo as an anti-diabetic and anti-atherogenic
      adipokine.
AB  - Genome-wide scanning is a powerful tool to identify susceptible chromosome loci,
      however, individual chromosomal regions still have many candidate genes. Although
      cDNA microarray analysis provides valuable information for identifying genes
      involved in pathogenesis, expression levels of many genes are changed. A novel
      approach for identification of therapeutic targets is the combination of genome
      wide scanning and the use of DNA chips, as shown in Fig. (1). Using DNA chips, we
      screened for secreted molecules, the expressions of which were changed in adipose
      tissues from mice rendered insulin resistance. Decreased expression of one of
      these molecules, adiponectin/Acrp30, correlates strongly with insulin resistance.
      Interestingly, recent genome-wide scans have mapped a susceptibility locus for
      type 2 diabetes and metabolic syndrome to chromosome 3q27, where adiponectin gene
      is located. Decreasing serum adiponectin levels are associated with increased
      risk for type 2 diabetes. Interestingly, adiponectin was decreased in insulin
      resistant rodent models both of obesity and lipoatrophy, and replenishment of
      adiponectin ameliorated their insulin resistance. Moreover, adiponectin
      transgenic mice ameliorated insulin resistance and diabetes Adiponectin knockout
      mice showed insulin resistance and glucose intolerance. In muscle and liver,
      adiponectin activated AMP kinase and PPARalpha pathways thereby increasing beta
      oxidation of lipids, leading to decreased TG content, which ameliorated insulin
      resistance under a high-fat diet. Despite similar plasma glucose and lipid levels
      on an apoE deficient background, adiponectin transgenic apoE deficient mice
      showed amelioration of atherosclerosis, which was associated with decreased
      expressions of class A scavenger receptor and tumor necrosis factor alpha.
      Finally, cDNA encoding adiponectin receptors (AdipoR1 and R2) have been
      identified by expression cloning, which facilitates the understanding of
      molecular mechanisms of adiponectin actions and obesity-linked diseases such as
      diabetes and atherosclerosis and the designing of novel antidiabetic and anti
      atherogenic drugs with AdipoR1 and R2 as molecular targets.

PMID- 14683456
TI  - Tissue-specific glucocorticoid reactivating enzyme, 11 beta-hydroxysteroid
      dehydrogenase type 1 (11 beta-HSD1)--a promising drug target for the treatment of
      metabolic syndrome.
AB  - Obesity is closely associated with the Metabolic Syndrome, which includes insulin
      resistance, glucose intolerance, dyslipidemia and hypertension. The best
      predictor of these morbidities is not the total body fat mass but the quantity of
      visceral (e.g. omental, mesenteric) fat. Glucocorticoids play a pivotal role in
      regulating fat metabolism, function and distribution. Indeed, patients with
      Cushing-s syndrome (a rare disease characterized by systemic glucocorticoid
      excess originating from the adrenal or pituitary tumors) or receiving
      glucocorticoid therapy develop reversible visceral fat obesity. The role of
      glucocorticoids in prevalent forms of human obesity, however, has remained
      obscure, because circulating glucocorticoid concentrations are not elevated in
      the majority of obese subjects. Glucocorticoid action on target tissue depends
      not only on circulating levels but also on intracellular concentration. Locally
      enhanced action of gluccorticoids in adipose tissue and skeletal muscle has been
      demonstrated in the Metabolic Syndrome. Evidence has accumulated that enzyme
      activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which
      regenerates active glucocorticoids from inactive forms and plays a central role
      in regulating intracellular glucocorticoid concentration, is commonly elevated in
      fat depots from obese individuals. This suggests a role for local glucocorticoid
      reactivation in obesity and the Metabolic Syndrome. 11beta-HSD1 knockout mice
      resist visceral fat accumulation and insulin resistance even on a high-fat diet.
      Furthermore, fat-specific 11beta-HSD1 transgenic mice, those have increased
      enzyme activity to a similar extent seen in obese humans, develop visceral
      obesity with insulin and leptin resistance, dyslipidemia and hypertension. In
      adipocytes, both antidiabetic PPARgamma agonists and LXRalpha agonists
      significantly reduce 11beta-HSD1 mRNA and enzyme activity, suggesting that
      suppression of 11beta-HSD1 in adipose tissue may be one of the mechanisms by
      which these drugs exert beneficial metabolic effects. Recently reported selective
      inhibitors of 11beta-HSD1 can ameliorate severe hyperglycemia in the genetically
      diabetic obese mice. In summary, 11beta-HSD1 is a promising pharmaceutical target
      for the treatment of the Metabolic Syndrome.

PMID- 14683457
TI  - DGAT: novel therapeutic target for obesity and type 2 diabetes mellitus.
AB  - Obesity is currently an exceptionally common problem in humans. The last several
      years have produced a significant number of breakthroughs in obesity related
      areas of investigation. Triglycerides are considered the main form of storage of
      excess calories in fat. A key enzyme in the synthesis of triglycerides is
      acylCoA: diacylglycerol acyltransferase (DGAT). Recent studies have shown that
      mice deficient in this enzyme are resistant to diet induced obesity and have
      increased insulin and leptin sensitivity. These effects suggest that inhibition
      of DGAT in vivo may be a novel therapeutic target not only for obesity but also
      for diabetes.

PMID- 14683458
TI  - Stearoyl-CoA desaturase-1 and the metabolic syndrome.
AB  - The incidence of obesity has increased dramatically in recent years, making it
      one of the most pressing public health concerns worldwide. Obesity is commonly
      associated with comorbid conditions, most notably diabetes, coronary artery
      disease, and hypertension, and the coexistence of these diseases has been termed
      the Metabolic Syndrome. The identification of the hormone leptin provided a
      molecular link to obesity. Leptin is recognized as the central mediator in an
      endocrine circuit regulating energy homeostasis. Leptin administration leads to
      hypophagia, increased energy expenditure, and weight loss, while leptin
      deficiency enacts an adaptive response to starvation manifested by hyperphagia,
      decreased energy expenditure, and suppression of the neuroendocrine axis. While
      elucidation of leptin's role has permitted a more detailed view of the biology
      underlying energy homeostasis, most obese individuals are leptin resistant. A
      more complete understanding of the molecular components of the leptin pathway is
      necessary to develop effective treatment for obesity and the Metabolic Syndrome.
      The identification and role of one such component, stearoyl-CoA desaturase-1 (SCD
      1), is reviewed here. Leptin's actions are not due to its anorectic effects
      alone. Leptin also mediates specific metabolic effects, including the potent
      depletion of triglyceride from liver and other peripheral tissues. To explore the
      molecular basis by which leptin depletes hepatic lipid, we used oligonucleotide
      arrays to identify genes in liver whose expression was modulated by leptin
      treatment. An algorithm was created that identified and ranked genes specifically
      repressed by leptin. The gene ranking at the top of this list was SCD-1, the rate
      limiting enzyme in the biosynthesis of monounsaturated fats. SCD-1 was
      specifically repressed during leptin-mediated weight loss, and mice lacking SCD-1
      showed markedly reduced adiposity on both a lean and ob/ob background
      (ab(J)/ab(J); ob/ob), despite higher food intake. ab(J)/ab(J); ob/ob mice also
      showed a complete correction of the hypometabolic phenotype and hepatic steatosis
      of ob/ob mice, suggesting that fatty acid oxidation is enhanced in the absence of
      SCD-1. These findings indicate that pharmacologic manipulation of SCD-1 may be of
      benefit in the treatment of obesity, diabetes, hepatic steatosis, and other
      components of the Metabolic Syndrome.

PMID- 14683460
TI  - SHIP2: an emerging target for the treatment of type 2 diabetes mellitus.
AB  - With the rapid increase in the number of patients developing type 2 diabetes
      mellitus and the lack of optimal therapies, much focus has been placed on the
      insulin-signaling pathway in the discovery of novel drug targets. Phosphatidyl
      Inositol 3-Kinase (PI3K) is central to mediating insulin-s metabolic effects.
      PI3K catalyzes the generation of phosphatidyl inositol (3,4,5) triphosphate
      (PIP(3)). Inhibition of PI3K activity results in a blockade of insulin signaling
      including glucose uptake and glyocogen synthesis. Thus, PIP(3) is a critical
      mediator of insulin action. A family of phosphatidyl inositol phosphatases have
      been identified that counter-regulate PI3K activity by hydrolyzing PIP(3) to
      phosphatidyl inositol bisphosphate at either the 3' or 5' position of the
      inositol ring. Mice lacking one of these enzymes, Src-Homology Inositol
      Phosphatase-2 (SHIP2), demonstrate increased insulin sensitivity, suggesting that
      pharmacological inhibition of SHIP2 could alleviate insulin resistance. Recent
      studies demonstrate elevated SHIP2 expression is associated with insulin
      resistance in human patients. Comparing the studies on SHIP2 and other
      phosphatases suggests how inhibition of SHIP2 leads to increased insulin
      sensitivity without deleterious effects. This review focuses on the emergence of
      SHIP2 as a target in the insulin-signaling pathway for the treatment of type 2
      diabetes.

PMID- 14683461
TI  - Protein-tyrosine phosphatase 1B as a potential drug target for obesity.
AB  - Obesity is increasing at an alarming rate and is considered by the World Health
      Organization as one of the top 10 epidemics worldwide. Resistance to leptin and
      insulin are likely to play a central role in obesity; thus, blocking inhibitors
      of these signaling pathways could prove useful in treating this disorder. Several
      lines of evidence have converged on protein tyrosine-phosphatase 1B (PTP1B) as
      one of the most important negative regulators of leptin as well as insulin
      signaling. Therefore, PTP1B appears to be a promising therapeutic candidate for
      the treatment of obesity. In this review, we discuss the role of PTP1B in leptin
      and insulin signaling, as well as its potential as a drug target in the treatment
      of obesity.

PMID- 14683459
TI  - Physiological roles of glycogen synthase kinase-3: potential as a therapeutic
      target for diabetes and other disorders.
AB  - Glycogen synthase kinase-3 (GSK-3) has perplexed signal transduction researchers
      since its detection in skeletal muscle 25 years ago. The enzyme confounds most of
      the rules normally associated with protein kinases in that it exhibits
      significant activity, even in resting, unstimulated cells. However, the protein
      is highly regulated and potently inactivated in response to signals such as
      insulin and polypeptide growth factors. The enzyme also displays a distinct and
      unusual preference for substrates that have been previously phosphorylated by
      other protein kinases which provides obvious opportunities for cross-talk. Its
      substrates are diverse and are predominantly regulatory molecules. The molecular
      cloning of the kinase revealed it to be encoded by two related but distinct
      genes. Moreover, the mammalian proteins showed remarkable similarity to a
      fruitfly protein isolated on the basis of its role in cell fate determination.
      From these humble beginnings, study of the enzyme has accrued further surprises
      such as its inhibition by lithium, its regulation by serine and tyrosine
      phosphorylation and its implication in several human disorders including
      Alzheimers disease, bipolar disorder, cancer and diabetes. Most recently, small
      molecule inhibitors of GSK-3 have been developed and assessed for therapeutic
      potential in several of models of pathophysiology. The question is whether
      modulation of such an "involved" enzyme could lead to selective restoration of
      defects without multiple unwanted side effects. This review summarizes current
      knowledge of GSK-3 with respect to its known functions, together with an
      assessment of its real-life potential as a drug target for chronic conditions
      such as type 2 diabetes.

PMID- 14683462
TI  - Therapeutic implications for immunophilin ligands in the treatment of
      neurodegenerative diseases.
AB  - There is a significant unmet need for therapeutic agents in the treatment of
      neurodegenerative diseases. Given their clinical importance, prototypical
      molecules that clearly exhibit both neuroprotective and neuroregenerative
      activities have been highly sought after. The journey led to the exploitation of
      neurotrophins, a family of proteins that had extraordinary therapeutic properties
      in pre-clinical models of neurodegeneration. Although experimentally promising,
      clinical development of neurotrophins for various neurological indications, such
      as Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and Parkinson's Disease
      was met with severe obstacles and setbacks, such as the inability to deliver
      these large proteins to target population of neurons, instability of the
      proteins, and non-specific activity. Immunophilins are proteins that act as
      receptors for immunosuppresant drugs, i.e. FK506 (tacrolimus), cyclosporin A, and
      rapamycin (sirolimus, Rapamune). Studies indicate immunophilins are expressed 10
      100 fold higher in CNS and PNS tissue than in immune tissue. Subsequent studies
      revealed potent neuroprotective and neuroregenerative properties of immunophilin
      ligands in both culture and animal models. In contrast to neurotrophins, most
      immunophilin ligands are highly stable, small molecules that can readily cross
      the blood-brain barrier and are orally bioavailable. Taken together, these data
      prompted the development of nonimmunosuppressive immunophilin ligands with potent
      therapeutic activities, although the potency of select compounds has come into
      question in more recent studies. This review will examine the experimental
      evidence supporting the use of immunophilin ligands for the treatment of
      neurodegenerative diseases and the current progression of these molecules in
      clinical trials.

PMID- 14683463
TI  - Exploring genetic influences on cognition: emerging strategies for target
      validation and treatment optimization.
AB  - Genomic research has produced an abundance of new candidate targets that remain
      to be validated as potential treatments for neuropsychiatric disorders.
      Functional neuroimaging, meanwhile, has provided detailed new insights into the
      neural circuits involved in emotional and cognitive control. At the growing
      interface between these independent lines of progress, new efforts are underway
      to unify our understanding of regional brain function with that of genetic and
      biochemical influences on behavior. Such a unified understanding of the
      mechanisms involved in cognitive and emotional control may open up new avenues
      for therapeutic intervention at the pharmacological and behavioral levels. In
      line with this, a new initiative sponsored by the National Institutes of Mental
      Health (NIMH) aims to bridge gaps between clinical diagnostics and the molecular
      processes that influence susceptibility to psychiatric disorders. A major goal of
      this initiative is to identify the neural and neurochemical substrates of basic
      cognitive processes that are disrupted in psychiatric disorders and to examine
      the influence of genetic factors at the cognitive level. This review describes
      some well-known findings that are at the forefront of this interface. The
      progress already made indicates that the goals of the new initiative are well
      founded and achievable.

PMID- 14683464
TI  - GABAergic functions and depression: from classical therapies to herbal medicine.
AB  - Classical medications employed to treat depression comprise mostly tricyclic
      antidepressants (TCAs), specific serotonin reuptake inhibitors (SSRIs) and
      monoamine oxidase inhibitors (MAOIs), in accord with the recognized involvement
      of serotonergic and adrenergic systems in depression. Other therapies such as
      electro-convulsive shock, lithium intake and psychotherapy work via as yet
      unknown mechanisms. Although GABAergic neurotransmitter systems have not been
      central to etiological hypotheses for depression, observations are accumulating
      to suggest that these systems might play an important role in the induction of
      the disease. Lines of evidence in this regard include interactions between
      GABAergic and other neurotransmitter systems in depression, GABA levels in
      patients before and after antidepressant treatments, GABA levels and up/down
      regulations of GABA receptors in animal models of induced depression, and
      clinical effects of GABA receptor ligands. Phytomedicines that have a long
      history of useful applications are drawing increasing attention in pharmaceutical
      research. Moreover, while drug development is usually focused on single
      constituent drugs on account of their more accurately predictable physiological
      responses, complex herbal formulae represent an increasingly important source of
      drug discovery given the advent of high-throughput screening and specific
      receptor binding assays. Their active constituents acting on different
      neurotransmitter systems could be identified, and their therapeutic efficacies
      tested rigorously. Along with new insights into the underlying mechanisms of
      depression, the rich abundance of chemical entities from herbs is becoming an
      inviting resource in the search for effective treatment. This review addresses
      recent research on the possible role of GABAergic receptors with regard to
      depression, and potentially antidepressant phytomedicines acting on this class of
      receptors.

PMID- 14683465
TI  - Cdk5 in the adult non-demented brain.
AB  - Cyclin-dependent kinase 5 (Cdk5), a Ser/Thr kinase, regulates the phosphorylation
      of neuronal proteins and thereby influences neuronal morphology, migration and
      axon growth. Tightly coordinated interactions between Cdk5 and its activator
      proteins p35 and p39 are critical for the developmental processes of post-mitotic
      neurons as well as functioning of the adult CNS. Excessive up-regulation of Cdk5
      activity leading to hyperphosphorylation of cytoskeletal proteins has been linked
      to neurodegenerative disorders, such as Alzheimer's disease (AD). On this basis
      it was proposed that Cdk5 might be a promising drug target. The physiologic role
      of Cdk5 in the adult CNS has been addressed recently. It was demonstrated that
      Cdk5 is involved in striatal and hippocampal neuronal plasticity and long-term
      behavioral changes associated with these processes. On the basis of the newly
      identified role of Cdk5 in synaptic plasticity, learning and memory the view that
      Cdk5 represents a good drug target in AD accompanied by cognitive dysfunctions
      may have to be revisited. Alternatively, targeting the mechanisms up-stream of
      Cdk5 leading to deregulation of Cdk5 activity, such as proteolytic cleavage of
      its activating subunits may prove to be more beneficial as a therapeutical
      approach.

PMID- 14683466
TI  - Therapeutic potential of 5-HT2C receptor antagonists in the treatment of anxiety
      disorders.
AB  - Anxiety disorders are the most common psychiatric illness affecting both adults
      and children. Following the observation that m-chlorophenylpiperazine(mCPP)
      induced anxiety-like states in patients and in animal models, it was shown that
      in man, mCPP behaves as a functionally selective agonist at the 5
      hydroxytryptamine (5-HT)2C receptor. This caused much interest in the development
      of antagonists at the 5-HT2C receptor for the treatment of anxiety disorders.
      This review examines the pre-clinical and clinical evidence for a role of the 5
      HT2C receptor in anxiety and evaluates the progress of compounds that target this
      therapeutic approach.

PMID- 14683467
TI  - Cannabinoids and memory: animal studies.
AB  - This review will consider studies concerning the effects of cannabinoid receptor
      agonists and antagonists on memory in laboratory animals. Two subtypes of
      cannabinoid receptors have been identified to date: the central CB1 subtype and
      the peripheral CB2 subtype. The receptor which specifically binds Delta9
      tetrahydrocannabinol (Delta9-THC) and related compounds in rat and human brain
      has been discovered and cloned by a number of researchers. This cannabinoid
      receptor is localized with high concentrations in different brain areas,
      including hippocampus and amygdala, which play an important role in the
      modulation of memory. In recent years evidence has been obtained that
      cannabinoids influence memory processes. It has been shown, for example, that
      Delta9-THC impairs memory in rats, mice and monkeys tested in a variety of
      experimental conditions (radial maze, instrumental discrimination tasks, Morris
      water maze, etc.). In some of these researches the effect of Delta9-THC was
      antagonized by the CB1 receptor antagonist SR 141716A, showing the involvement of
      this subtype of cannabinoid receptor in its effect. Anandamide,
      arachidonylethanolamide, was recently discovered as the first endogenous ligand
      for the cannabinoid receptor. It has been reported to stimulate CB1 receptors and
      to mimic the pharmacological effects of cannabinoids. Experiments carried out by
      our group have shown that anandamide impairs memory consolidation in random bred
      mice (CD1), exerts genotype-dependent influences on memory in inbred strain of
      mice (C57 BL/6 and DBA/2), and that opioid and dopaminergic systems might be
      involved in its effects.

PMID- 14683468
TI  - Extracellular ATP and neurodegeneration.
AB  - ATP is a potent signaling molecule abundantly present in the CNS. It elicits a
      wide array of physiological effects and is regarded as the phylogenetically most
      ancient epigenetic factor playing crucial biological roles in several different
      tissues. These can range from neurotransmission, smooth muscle contraction,
      chemosensory signaling, secretion and vasodilatation, to more complex phenomena
      such as immune responses, pain, male reproduction, fertilization and embryonic
      development. ATP is released into the extracellular space either exocytotically
      or from damaged and dying cells. It is often co-released with other
      neurotransmitters and it can interact with growth factors at both receptor-
      and/or signal transduction-level. Once in the extracellular environment, ATP
      binds to specific receptors termed P2. Based on pharmacological profiles, on
      selectivity of coupling to second-messenger pathways and on molecular cloning,
      two main subclasses with multiple subtypes have been distinguished. They are P2X,
      i.e. fast cation-selective receptor channels (Na+, K+, Ca2+), possessing low
      affinity for ATP and responsible for fast excitatory neurotransmission, and P2Y,
      i.e. slow G protein-coupled metabotropic receptors, possessing higher affinity
      for the ligand. In the nervous system, they are broadly expressed in both neurons
      and glial cells and can mediate dual effects: short-term such as
      neurotransmission, and long-term such as trophic actions. Since massive
      extracellular release of ATP often occurs after metabolic stress, brain ischemia
      and trauma, purinergic mechanisms are also correlated to and involved in the
      etiopathology of many neurodegenerative conditions. Furthermore, extracellular
      ATP per se is toxic for primary neuronal dissociated and organotypic CNS cultures
      from cortex, striatum and cerebellum and P2 receptors can mediate and aggravate
      hypoxic signaling in many CNS neurons. Conversely, several P2 receptor
      antagonists abolish the cell death fate of primary neuronal cultures exposed to
      excessive glutamate, serum/potassium deprivation, hypoglycemia and chemical
      hypoxia. In parallel with these detrimental effects, also trophic functions have
      been extensively described for extracellular purines (both for neuronal and non
      neuronal cells), but these might either aggravate or ameliorate the normal
      cellular conditions. In summary, extracellular ATP plays a very complex role not
      only in the repair, remodeling and survival occurring in the nervous system, but
      even in cell death and this can occur either after normal developmental
      conditions, after injury, or acute and chronic diseases.

PMID- 14683469
TI  - Stress and angiotensin II: novel therapeutic opportunities.
AB  - Angiotensin II was initially described as a hormone of peripheral origin, the
      active end product of the Renin-Angiotensin System. The subsequent discovery that
      Angiotensin II was locally formed and selectively regulated in most organs
      indicated that tissue Angiotensin II systems might play additional important
      roles. After initial controversy, the presence of an Angiotensin II system in the
      brain is now universally accepted. Brain Angiotensin II is probably involved in
      the regulation of many brain functions. Angiotensin II AT1 receptors are
      localized not only in areas related to the regulation of autonomic and endocrine
      control, but also in many other areas of the brain involved in emotional, sensory
      and motor functions. Angiotensin II AT2 receptors are more abundant in brain
      areas related to sensory and motor control. The roles of brain Angiotensin II
      appear to be multiple and complex. In addition to a regulatory role in the
      control of the autonomic and hormone systems, the peptide participates in brain
      development, sensory processes, cognition and in the regulation of
      cerebrovascular flow. Recent developments indicate that blockade of the brain
      Angiotensin II AT1 receptors not only contributes to a significant blood pressure
      decrease in hypertension, but that simultaneous antagonism of peripheral and
      brain AT1 receptors reduces the sympathoadrenal and hormonal responses to stress
      and prevents stress-induced gastric injury. A novel role emerges for the use of
      peripheral and centrally acting AT1 receptor antagonists as therapeutically
      advantageous for the treatment of stress-related disorders.

PMID- 14683470
TI  - Re-establishment of a normal apoptotic process as a therapeutic approach in B
      CLL.
AB  - Even though the capacity of B-CLL leukemic cells to proliferate has been
      underestimated until recently, the accumulation of tumor cells in patients mostly
      results from a defect in the apoptotic program. Several mechanisms can account
      for this deficient cell death pathway. These include overexpression of anti
      apoptotic molecules such as members of the Bcl-2 family, which control the
      opening of the mitochondrial transition permeability pore, and of the IAP
      (inhibitors of apoptosis) family, which inhibit the activity of caspases. The
      latter is also suppressed by nitric oxide (NO) released through an inducible NO
      synthase present in the leukemic cells. The activity of the receptors with a
      death domain (Fas, TRAIL) is impaired, thus contributing to the resistance to
      spontaneous and/or drug-induced apoptosis. Interferons as well as several
      cytokines and angiogenic factors are also involved in the failure of programmed
      cell death, either by providing efficient signals for survival (BAFF) or by
      counteracting the apoptotic process. A better knowledge of the mechanisms of
      survival and escape from apoptosis of B-CLL cells has led to the proposal of new
      drugs that selectively interfere at the different steps of these cascades. Their
      study is complicated by the lack of suitable cell lines and pre-clinical models.
      Nevertheless, some of these chemotherapeutic agents appear to be promising,
      provided they are correctly targeted to the leukemic cells.

PMID- 14683471
TI  - An update on new anticoagulants.
AB  - A variety of new anticoagulants for the prevention and treatment of venous and
      arterial thromboembolism are under development. Designed to overcome the
      limitations of heparin and vitamin K antagonists, these new agents are at various
      stages of clinical testing. This paper reviews venous and arterial
      thrombogenesis, discusses the regulation of coagulation, identifies the molecular
      targets for new anticoagulants, describes new anticoagulants in more advanced
      stages of clinical testing, and provides perspective on how these agents will
      impact on practice.

PMID- 14683472
TI  - Selective protein kinase C inhibitors and their applications.
AB  - Protein kinase C (PKC) represents a family of phospholipid-dependent
      serine/threonine kinase. PKC was detected in almost all types of cells and
      tissues in the body. The activation of PKC is involved in the signal regulation
      of many physiological and pathological processes. PKC has multiple isoforms
      (alpha, betaI, betaII, gamma delta, epsilon, eta, theta, xi, iota and micro). PKC
      mediated cellular processes are tissue- and isoform-specific. Investigations on
      selective or isoform-specific PKC inhibitors have attracted great attention
      during last two decades. Recent studies demonstrated that LY333531, a PKC-beta
      specific inhibitor, reduced the development of diabetic vascular complications in
      animal models and prevented hyperglycemia-induced impairment of endothelial
      dependent vasodilation in healthy subjects. Results from phase I clinical trial
      suggested low risk of the inhibitor. Phase III clinical trials on the safety and
      the preventive effects of the PKC-beta-specific inhibitor on diabetic
      complications are under progress. The efficacy of ISSI-3521, a PKC-alpha
      antisense inhibitor, on slowing the growth and metastasis of solid tumors is
      currently being examined in clinical trials. Partial responses in the prevention
      of the progress of malignancies were found in early phases of clinical trials for
      UCN-01 and CGP41251, two partially isoform-specific PKC inhibitors. Recent
      findings suggest that isoform-specific PKC inhibitors are potentially beneficial
      to the prevention or treatment of some common diseases, including cancers and
      diabetic vascular complications. Safety and efficacy studies of the PKC
      inhibitors will be required through large-scale long-term clinical trials.

PMID- 14683473
TI  - Leukocyte recruitment to atherosclerotic lesions, a complex web of dynamic
      cellular and molecular interactions.
AB  - The accumulation of leukocytes in atherosclerotic lesions is of fundamental
      importance in the development of atherosclerosis. Consequently, the adhesive and
      signaling mechanisms responsible for leukocyte invasion in the arterial wall have
      been intensively studied as potential targets for therapeutic intervention.
      During recent years, it has become increasingly clear that leukocyte recruitment
      in atherosclerosis is mediated by a complex series of cellular and molecular
      interactions that in many ways resemble those that take place in tissue
      inflammation. However, certain aspects of leukocyte recruitment in
      atherosclerosis are specific for this disease and present themselves as
      interesting drug targets. This review summarizes the current knowledge about the
      mechanisms that guide the extravasation of leukocytes to inflamed tissues, with
      special focus on atherosclerotic lesions. Moreover, novel experimental techniques
      are described, techniques that allow for the study of dynamic events taking place
      in atherosclerosis and that have provided interesting insights into lesion
      pathology. The data reviewed contribute to the understanding of atherosclerosis,
      and may help in the development of treatment strategies for a disease that is a
      major contributor to morbidity and mortality in the western world today.

PMID- 14683474
TI  - Drug induced QT prolongation: lessons from congenital and acquired long QT
      syndromes.
AB  - Recent developments regarding the underlying genetic and intracardiac ion channel
      causes of congenital long QT syndrome have shed new light in the area of
      repolarization disorders and their resultant cardiac arrhythmias. Drug induced or
      acquired QT prolongation often represents a latent form of congenital long QT
      syndrome, though the genetic basis of this has not been elucidated in the
      majority of cases. Understanding this has lead to a new concept of repolarization
      reserve, a measure of inherent susceptibility to repolarization-mediated
      arrhythmias. The majority of pharmacologic agents that cause significant QT
      prolongation have potassium channel blocking characteristics, predominantly
      affecting the rapidly activating current I(Kr). The list of agents known to
      affect I(Kr)continues to grow, best monitored through several websites that
      collate reports of drug-induced QT prolongation and arrhythmias. Discontinuation
      of the offending agent and supportive care are often all that is necessary when
      clinical arrhythmias arise.

PMID- 14683475
TI  - Design of ester prodrugs to enhance oral absorption of poorly permeable
      compounds: challenges to the discovery scientist.
AB  - Many drugs are administered at sites that are remote from their site of action.
      The most common route of drug delivery is the oral route. The optimal
      physicochemical properties to allow high transcellular absorption following oral
      administration are well established and include a limit on molecular size,
      hydrogen bonding potential and adequate lipophilicity. For many drug targets,
      synthetic strategies can be devised to balance the physicochemical properties
      required for high transcellular absorption and the SAR for the drug target.
      However, there are drug targets where the SAR requires properties at odds with
      good membrane permeability. These include a requirement for significant polarity
      and groups that exhibit high hydrogen bonding potential such as carboxylic acids
      and alcohols. In such cases, prodrug strategies have been employed. The rationale
      behind the prodrug strategy is to introduce lipophilicity and mask hydrogen
      bonding groups of an active compound by the addition of another moiety, most
      commonly an ester. An ideal ester prodrug should exhibit the following
      properties: 1). Weak (or no) activity against any pharmacological target, 2).
      Chemical stability across a pH range, 3). High aqueous solubility, 4). Good
      transcellular absorption, 5). Resistance to hydrolysis during the absorption
      phase, 6). Rapid and quantitative breakdown to yield high circulating
      concentrations of the active component post absorption. This paper will review
      the literature around marketed prodrugs and determine the most appropriate
      prodrug characteristics. In addition, it will examine potential Discovery
      approaches to optimising prodrug delivery and recommend a strategy for
      prosecuting an oral prodrug approach.

PMID- 14683476
TI  - Akt in prostate cancer: possible role in androgen-independence.
AB  - Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), has often
      been implicated in prostate cancer. Studies in prostate tumor cell lines revealed
      that Akt activation is probably important for the progression of prostate cancer
      to an androgen-independent state. Investigations of human prostate cancer tissues
      show that although there is neither Akt gene amplification nor enhanced protein
      expression in prostate cancer compared to normal tissue, poorly differentiated
      tumors exhibit increased expression of a phosphorylated (activated) form of Akt
      compared to normal tissue, prostatic intraepithelial neoplasia (PIN) or well
      differentiated prostate cancer. Akt phosphorylation is accompanied by the
      inactivation of ERK, a member of the mitogen activated protein kinase (MAPK)
      family. In this article, we postulate that Akt promotes androgen-independent
      survival of prostate tumor cells by modulating the expression and activation of
      the androgen receptor (AR).

PMID- 14683477
TI  - The role of estrogen and estrogen-related drugs in cardiovascular diseases.
AB  - The cardiovascular effects of estrogen have recently become a focus of basic and
      clinical cardiovascular medicine because of the multiplicity of its beneficial
      effects. Various basic and clinical studies have revealed that estrogen has
      potent cardiovascular effects against ischemic or non-ischemic injury of the
      heart and vessels, leading to the concept that administration of estrogen may
      reduce cardiovascular disease in postmenopausal women. Indeed, among the groups
      of the postmenopausal women who have a higher risk of cardiovascular diseases,
      the hormone therapy has been associated with improved outcomes for cardiovascular
      events. Estrogen binds to the estrogen receptor, which is a member of the steroid
      hormone family of nuclear receptors and is the estrogen response element in
      target genes, leading to the transcriptional regulation of many genes. In
      addition to these genomic effects of estrogen, it has been recently reported that
      estrogen can have rapid "nongenomic" effects. In contrast to such data, recent
      clinical prevention trials in postmenopausal women treated with a combination of
      estrogen and progestins have not revealed any beneficial effects on
      cardiovascular morbidity or mortality, and estrogen itself increases the risk of
      endometrial and breast cancer. Under these circumstances, a selective estrogen
      receptor modulator (SERM), which exerts estrogenic agonistic or antagonistic
      actions on various tissues, has been recently introduced for new hormone therapy
      because it reduces the adverse effects of estrogen. Here, we summarize the
      effects of estrogen and SERM on the cardiovascular system and discuss cellular
      mechanisms that may be involved.

PMID- 14683478
TI  - Pharmacogenetics of estrogen metabolism and transport in relation to cancer.
AB  - Exposure to estrogens has been long associated with the genesis of human
      malignancies, including breast, ovarian, and endometrial cancer. A variety of
      phase I and II enzymes are involved in the metabolic activation and de-activation
      of estrogens, including cytochrome p450 isoforms, estrone sulfatase,
      sulfotransferases, catechol-o-methyltransferase, and uridine-5'-diphosphate
      glucuronosyltransferase. In addition, at least one ATP-binding cassette gene
      (i.e., ABCG2) is involved in estrogen transport. Variability in the expression
      levels of these proteins may have important consequences for an individual-s
      susceptibility to certain malignancies. Naturally occurring variants in the genes
      involved in estrogen exposure levels have been identified that might affect
      protein function and expression. This review focuses on recent advances in the
      pharmacogenetics of these proteins, and discusses potential clinical
      ramifications of these genetic variants.

PMID- 14683479
TI  - Transcriptional regulation of cytochrome p450 2B genes by nuclear receptors.
AB  - Cytochrome p450 2B genes have been used extensively as prototypical models to
      study phenobarbital induction of p450 enzymes. Although its basal hepatic
      abundance is relatively low, CYP2B is highly inducible by various chemicals.
      Cross regulation and shared substrate specificity of CYP2B with CYP3A and other
      drug metabolizing enzymes lend support to the pharmacological and toxicological
      significance of CYP2B induction. The constitutive androstane receptor (CAR)
      appears to be one of the main regulators involved in transcriptional activation
      of CYP2B genes, although pregnane X receptor (PXR), glucocorticoids receptor
      (GR), and other nuclear receptors may be required for their optimal activation.
      In this article, we review current advances in the mechanisms of species-specific
      activation of CYP2B genes by CAR, with the human CYP2B6 gene being a main focus.
      Several recent findings, including discovery of a human CAR specific activator 6
      (4-chlorophenyl:imidazo[2,1-b]thiazole-5carbaldehyde O-(3,4-dichlorobenzyl)oxime
      (CITCO), identification of a far-distal xenobiotic-responsive enhancer module
      (XREM) in the CYP2B6 gene promoter, and generation of CAR-null mice as a model of
      characterizing CAR target gene expression, will also be discussed. These findings
      should provide greater insight into the mechanisms and species-specific
      differences of CAR regulation of CYP2B and other target genes.

PMID- 14683480
TI  - Reaction phenotyping in drug discovery: moving forward with confidence?
AB  - For the pharmaceutical industry, one of the challenges in evaluating the risk of
      future compound attrition at the discovery stage is the successful prediction of
      the major routes of clearance in humans. For compounds cleared by metabolism,
      such information will help to avoid the development of compounds that will
      exhibit large interpatient differences in pharmacokinetics via 1). routes of
      metabolism catalyzed by functionally polymorphic enzymes and/or 2). clinically
      significant metabolic drug-drug interactions, in the later stages of development.
      The degree of intersubject variability that is acceptable for a drug candidate is
      uncertain in the discovery stage where knowledge of other important factors is
      limited or unavailable (i.e. therapeutic index, pharmacodynamic variability,
      etc). Reaction phenotyping is the semi-quantitative in vitro estimation of the
      relative contributions of specific drug-metabolizing enzymes to the metabolism of
      a test compound. However, reaction phenotyping in the discovery stage of drug
      development is complicated by the absence of radiolabelled parent compound or
      metabolite bioanalytical standards relative to later stages of development. In
      this commentary, some of the approaches, based on published data, which can be
      taken to overcome these challenges are discussed. In addition, knowledge of the
      molecular structure (i.e. specific chemical substituents), physicochemical
      properties, and routes of clearance in animals can all help in making a
      successful prediction for the routes of clearance in humans. In combination, the
      objective of these studies should be to reduce to a minimum the risk of finding
      significant inter-patient differences in pharmacokinetics at a later stage in
      development due to significant metabolism by polymorphic enzymes or drug-drug
      interactions. Consequently, this data should be used to avoid costly late stage
      attrition.

PMID- 14683481
TI  - Increasing the throughput and productivity of Caco-2 cell permeability assays
      using liquid chromatography-mass spectrometry: application to resveratrol
      absorption and metabolism.
AB  - The Caco-2 cell monolayer permeability assay has become a standard model of human
      intestinal absorption and transport. This paper reviews recent progress in
      increasing the throughput of Caco-2 cell monolayer assays and in expanding the
      scope of this assay to include modeling intestinal drug metabolism. The state-of
      the-art in Caco-2 cell monolayer permeability assays combines multi-well plates
      fitted with semi-permeable inserts on which Caco-2 cells have been cultured with
      liquid chromatography-mass spectrometry (LC-MS) or LC-tandem mass spectrometry
      (LC-MS-MS) for the quantitative analysis of test compounds and the identification
      of their intestinal metabolites. After reviewing the progress in increasing the
      throughput of Caco-2 cell monolayer assays for both modeling human intestinal
      permeability or transport and the metabolism of xenobiotic compounds, we
      demonstrate the application of LC-MS and LC-MS-MS to the measurement of
      resveratrol permeability and metabolism in the Caco-2 model. trans-Resveratrol
      (trans-3,5,4'-trihydroxystilbene) is a polyphenolic compound occurring in grapes,
      peanuts and other food sources, that is under investigation as a cancer
      chemoprevention agent. The apparent permeability coefficient for apical (AP) to
      basolateral (BL) movement of resveratrol was 2.0 x 10(-5)cm/sec. Resveratrol was
      not a substrate for P-glycoprotein or the multi-drug resistance associated
      proteins (MRP). No phase I metabolites were observed, but the phase II conjugates
      resveratrol-3-glucuronide and resveratrol-3-sulfate was identified based on LC-MS
      and LC-MS-MS analysis and comparison with synthetic standards. Although these
      data indicate that resveratrol diffuses rapidly across the intestinal epithelium,
      extensive phase II metabolism during absorption might reduce resveratrol
      bioavailability.

PMID- 14683482
TI  - Cytokine antibody arrays: a promising tool to identify molecular targets for drug
      discovery.
AB  - Cytokines play important roles in normal cell functions and changes in cytokines
      have been implicated in many diseases. Recent efforts have focused on developing
      cytokine antibody arrays. These arrays allow investigators to simultaneously
      detect multiple cytokines in qualitative and quantitative ways. Cytokine antibody
      array systems feature high sensitivity, specificity and throughput. This novel
      technology opens up an expanding spectrum of applications in drug discovery,
      including target discovery, target validation, screening for lead compounds,
      compound optimization and clinical trials.

PMID- 14683483
TI  - Advances in high-throughput screening: biomolecular interaction monitoring in
      real-time with colloidal metal nanoparticles.
AB  - The post-genomic era is revolutionizing the drug discovery process. The new
      challenges in the identification of therapeutic targets require efficient
      technological tools in order to be properly addressed. Label-free detection
      systems use proteins or ligands coupled to materials of which the physical
      properties are measurably modified upon specific interactions. Among the label
      free systems currently available, the use of metal nanocolloids offers enhanced
      throughput and flexibility for real-time biomolecular recognition monitoring at a
      reasonable cost.

PMID- 14683484
TI  - Homogeneous time resolved fluorescence assay to measure histamine release.
AB  - Histamine is a biogenic amine synthesized by the enzymatic decarboxylation of
      histidine. Implication of histamine in allergy is well described but histamine is
      also found in some specific neurones, functions as a neurotransmitter and
      regulates sleep/wake cycles, hormonal secretion, cardiovascular control and
      thermo-regulation. We have developed a TR-FRET histamine assay, based on the
      competition between sample histamine and allophycocyanine (XL665) labelled
      histamine for binding to a Europium cryptate (EuK) labelled antibody. As
      histamine is a small monoamine molecule, high affinity antibodies have been
      raised against carrier protein conjugated histamine. Therefore, sample histamine
      needs to be derivatized in the same way as the conjugated histamine, so that the
      antibody will have a similar affinity for both molecules. This acylation step is
      performed directly in wells and does not need to be done in separate vials,
      making handling easier for large numbers of samples. The incubation takes place
      at room temperature for 3 hours. The assay covers a measurement range of 1.56 to
      400 nM and shows an analytical sensitivity of 1.3nM. We have shown that
      miniaturization of sample and reagents volumes down to 20 micro l does not alter
      these performances. This histamine release assay provides a particularly well
      adapted procedure for HTS and secondary screening compared to current
      heterogeneous methods.

PMID- 14683485
TI  - Numerical characterization and similarity analysis of DNA sequences based on 2-D
      graphical representation of the characteristic sequences.
AB  - Based on the classifications of the four nucleic acid bases, He and Wang reduced
      a DNA sequence to three binary sequences, which are called the characteristic
      sequences (J. Chem. Inf. Comput. Sci. 42 (2002) 1080). In this paper, we
      associate each characteristic sequence with a (b)L / (b)L matrix by giving a 2-D
      'two horizontal lines' graphical representation, and thus obtain a 3-component
      vector with entries being the sums of the maximal and minimal eigenvalues of the
      (b)L / (b)L matrices. The introduced vector results in more simple
      characterizations and comparisons among the coding sequences of exon 1 of beta
      globin gene of eleven different species.

PMID- 14683486
TI  - Structural, chemical topological, electrotopological and electronic structure
      hypotheses.
AB  - The first important hypothesis in the prediction of properties of synthesized
      molecules is the structural hypothesis. In the study of drug-receptor
      interactions, the case where the three-dimensional structure of the receptor is
      known allows the application of molecular simulation and energy calculations to
      estimate the binding affinity for a proposed series of compounds. The chemical
      topological hypothesis permits the description of molecular structures without
      using concepts such as force or energy. These notions would not be as dominant as
      supposed since they should be able to be deduced from topology. Although
      topological descriptors are able to describe specific physicochemical properties,
      there is no any mechanistic interpretation for topological descriptors, but they
      can be considered as essential magnitudes, able to describe molecular structure
      as an alternative and independent approach, since they allow an algebraic
      description of the structure itself. The hypothesis is based on the ability of
      topological descriptors for the prediction of virtually any kind of structure
      related macroscopic property, and to design directly new compounds showing
      predetermined properties. It is possible to design new lead drugs ignoring the
      explicit mechanism of action, but only by topological similarity with other
      active compounds. This is a basic difference with all the conventional methods
      based on the use of physical variables, which need to know the specific drug
      receptor interaction. The electrotopological hypothesis may be considered a
      synthesis of both previous hypotheses. Finally, the electronic structure
      hypothesis is formulated.

PMID- 14683487
TI  - The application of artificial neural networks for the selection of key
      thermoanalytical parameters in medicinal plants analysis.
AB  - In the present study three thermoanalytical methods: differential thermal
      analysis (DTA), thermogravimetric analysis (TGA), and derivative
      thermogravimetric analysis (DTG) were used to investigate the thermal behavior of
      medicinal plant raw materials. In order to describe DTA curve, designation of the
      onset T(i), and peak T(p), temperatures was required. In TGA the mass losses
      Delta(m), and in DTG the temperature range of peak DeltaT, peak temperature T(p),
      and peak height h, were recorded. All parameters were read for three stages of
      the thermal decomposition of plant samples which resulted in obtaining eighteen
      thermal variables for each sample. Some similarities in the course of thermal
      decomposition of the same plant organs were recognized, but complexity of the
      obtained data made it very difficult to determine if they could differentiate
      between medicinal plant materials and which of them encode the most valuable
      information about the studied herbals. In order to confirm the existence of any
      relations between the chemical composition of medicinal plants and their thermal
      decomposition and to find out which thermoanalytical variables or decomposition
      stages can be considered as the most significant in terms of their evaluation, it
      was decided to apply fully connected feed-forward artificial neural networks
      (ANN). Two different training algorithms were used to address the problem: back
      propagation of error and conjugate gradient descent. To verify the results two
      dimensional (2-D) Kohonen self-organizing feature maps (SOFMs) were employed. Two
      alternative datasets of thirteen key variables discriminating plant samples have
      been proposed.

PMID- 14683488
TI  - Parallel and multiplexed bead-based assays and encoding strategies.
AB  - Advances in high throughput screening (HTS), together with the rapid progress in
      combinatorial chemistry, genomic and proteomic sciences have dramatically
      stimulated the development of a variety tools to enable the drug discovery
      process to become more efficient. Major future challenges in HTS include
      obtaining high density and good quality data based on assays that are rapid,
      reliable, inexpensive, sensitive, simple and miniaturised. This paper reviews the
      development and role of bead-based assays for HTS including DNA and single
      nucleotide polymorphism (SNP) assays, particularly from a multiplex perspective
      and evaluating the recent advances in bead-based arrays. The encoding strategies
      that are commonly used in bead-based assays are highlighted, while the importance
      of magnetic beads in genomic and proteomic purifications is discussed. In
      conclusion, bead-based assays offer a powerful promising approach for many
      aspects of drug discovery.

PMID- 14683489
TI  - PEG based resins for protease drug discovery synthesis, screening and analysis of
      combinatorial on-bead libraries.
AB  - This review will cover the entire hit identification process performed with
      biocompatible, aqueous solvated, poly[ethylene glycol] (PEG) based resins - from
      synthesis, through screening, to analysis. The different types of resins
      (including their preparation) will be discussed and compared individually.
      Examples of one-bead-one-compound substrate libraries will be presented, as will
      one-bead-two-compounds libraries used for the discovery of enzyme inhibitors. The
      review includes a section covering organic and bio-organic reactions performed on
      all-PEG resins and discusses on-bead screening of the libraries with
      biomolecules. Finally, analysis of compounds on single beads, either via
      investigation by on-bead NMR or by ladder-coding of the combinatorial compound is
      covered. In general, the review will focus on chemistry, libraries, synthesis,
      screening, and analysis, using all-PEG based resins.

PMID- 14683490
TI  - Chemogenomics with peptide secondary structure mimetics.
AB  - There is increasing evidence that redox regulation of transcription, particularly
      activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappaB), is important
      in inflammatory diseases. Human thioredoxin (TRX), a member of the oxidoreductase
      superfamily, was initially identified, as a factor which augments the production
      of interleukin-2 receptor alpha (IL-2R alpha) in human T-cell lymphotropic virus
      type 1 (HTLV-1) infected patient T-cells. Substrates for the redox activity of
      TRX bind the active site cleft in extended strand structure. The rapid generation
      of high numbers of peptide secondary structure mimetics through solid-phase
      synthesis is a key technology for the identification of pharmaceutical leads
      based on such protein-peptide interactions. In this manuscript, we describe a
      chemogenomic approach utilizing an extended strand templated library to develop
      small molecule inhibitors to validate oxidoreductase molecular targets in a
      murine asthma model.

PMID- 14683491
TI  - Forward & reverse chemical genetics using SPOS-based combinatorial chemistry.
AB  - Combinatorial chemistry is being applied to diverse problems in the biological
      and pharmaceutical sciences. This review will describe an emerging application
      called "chemical genetics" or "chemical genomics" - genetics and genomics are
      often used interchangeably in this context. In forward chemical genomics,
      chemical libraries are tested in living systems to discover compounds that cause
      a desirable effect. Subsequently, the protein target is identified using various
      biochemical and molecular biological tools. By this method, we gain insights into
      the inner workings of life, and indeed, in some forms this has been the path by
      which most of the pharmacopoeia was discovered. In reverse chemical genetics,
      proteins of interest are used to probe compound collections, and those compounds
      that bind the proteins of interest are used to treat living systems and observed
      for interesting biological responses. Plausible biological roles of these
      proteins are inferred from the effects of the compounds because they are assumed
      to generally inhibit, or more rarely, stimulate, the protein's functions.
      Interestingly, the reverse genetic approach is emerging as the leading model for
      drug discovery today. Different methods and cases will be described to illustrate
      forward and reverse paradigms, including those developed in the author's
      laboratory.

PMID- 14683492
TI  - Library design practices for success in lead generation with small molecule
      libraries.
AB  - The generation of novel structures amenable to rapid and efficient lead
      optimization comprises an emerging strategy for success in modern drug discovery.
      Small molecule libraries of sufficient size and diversity to increase the chances
      of discovery of novel structures make the high throughput synthesis approach the
      method of choice for lead generation. Despite an industry trend for smaller, more
      focused libraries, the need to generate novel lead structures makes larger
      libraries a necessary strategy. For libraries of a several thousand or more
      members, solid phase synthesis approaches are the most suitable. While the
      technology and chemistry necessary for small molecule library synthesis continue
      to advance, success in lead generation requires rigorous consideration in the
      library design process to ensure the synthesis of molecules possessing the proper
      characteristics for subsequent lead optimization. Without proper selection of
      library templates and building blocks, solid phase synthesis methods often
      generate molecules which are too heavy, too lipophilic and too complex to be
      useful for lead optimization. The appropriate filtering of virtual library
      designs with multiple computational tools allows the generation of information
      rich libraries within a drug-like molecular property space. An understanding of
      the hit-to-lead process provides a practical guide to molecular design
      characteristics. Examples of leads generated from library approaches also provide
      a benchmarking of successes as well as aspects for continued development of
      library design practices.

PMID- 14683493
TI  - Chemical libraries towards protein kinase inhibitors.
AB  - Over 500 human protein kinases identified to date are susceptible to play crucial
      roles in the regulation of many signal transduction pathways, making them
      significant drug discovery targets. However, their active sites share a high
      level of similarity, which constitutes a major challenge in the finding of
      selective and safe inhibitors. In order to meet this challenge, whether via
      traditional or alternative approaches, the use of chemical libraries to find
      either unknown natural ligands or specific inhibitors of particular kinases is
      more important than ever. This review briefly summarizes the recent literature on
      such libraries of peptides, natural product analogues, and small molecules.
      Significant chemical scaffolds, some synthetic routes particularly on solid-phase
      support, and computational tools employed for the efficient design of both
      selective and bioavailable inhibitors are highlighted.

PMID- 14683494
TI  - Natural product-like and other biologically active heterocyclic libraries using
      solid-phase techniques in the post-genomic era.
AB  - High-throughput technologies allow the selection of new biological targets for
      drug discovery in the post-genomic era. These tools increase the need of new
      methods to rapidly obtain potent small molecules and natural products to discover
      new lead structures. In particular, the solid-phase synthesis offers a great
      potential to obtain large compound sets.

PMID- 14683495
TI  - Use of multicomponent, domino, and other one-pot syntheses on solid phase:
      powerful tools for the generation of libraries of diverse and complex compounds.
AB  - The availability of small organic molecules covering as much chemical space as
      possible is seen as the only means that guarantees potential modulation of the
      many biological targets that are ultimately being unveiled by genomics. Therefore
      diversity oriented organic synthesis is rapidly becoming one of the paradigms in
      the process of modern drug discovery. This has spurred research in those fields
      of chemical investigation that lead to the rapid assembly of not only molecular
      diversity, but also molecular complexity. As a consequence multi-component as
      well as domino or related reactions are witnessing a new spring. Coupling these
      one-pot processes with solid-phase synthesis offers new perspectives for the
      preparation of both primary and thematic libraries. The progresses recently made
      in this field that perfectly suits the needs of modern drug discovery are the
      subject of the present review.

PMID- 14683496
TI  - Application of non-covalently solid-phase bound catalysts.
AB  - Supported catalysts have become valuable tools for simplified product isolation
      and catalyst recycling. The common method is covalent attachment to a solid
      support. An alternative strategy is to immobilize catalysts by non-covalent
      bonding through hydrogen bridges, ionic, hydrophobic or fluorous interactions.
      Compared to covalent attachment, such non-covalent approaches increase the
      flexibility in the choice of the support-material, reaction conditions and work
      up strategies. Numerous catalytic reactions employing one of these non-covalent
      fixation strategies have meanwhile appeared in the literature.

PMID- 14683497
TI  - High resolution magic angle spinning NMR for analyzing small molecules attached
      to solid support.
AB  - Solid phase synthesis has become a routine technique in combinatorial chemistry.
      The need in analytical methods to characterize nondestructively resin bound
      molecules has been fulfilled by the introduction of High Resolution Magic Angle
      Spinning (HR MAS) NMR of solvent swollen beads. HR MAS NMR can give solution like
      proton NMR spectra and one- and two-dimensional NMR techniques are amenable,
      allowing detailed structure analysis. Recent developments are the application of
      a diffusion filter to suppress solvent signals and dipolar recoupling techniques
      to gain spatial information. HR MAS NMR has been applied to monitor reactions and
      elucidate reaction products.

PMID- 14683498
TI  - Hypoxia inducible factor as a cancer drug target.
AB  - Solid tumors with areas of hypoxia are the most aggressive and difficult tumors
      to treat and are a major reason for treatment failure. Previous attempts to treat
      hypoxic tumors have been largely unsuccessful and new agents are needed. The
      cellular response to hypoxia is controlled by the hypoxia inducible factor-1 (HIF
      1) transcription factor. HIF-1 consists of an oxygen regulated alpha subunit and
      a constitutively expressed beta subunit, which bind and translocate to the
      nucleus to activate transcription of a range of genes involved in increasing
      glycolysis, inhibition of apoptosis and promotion of angiogenesis and metastasis.
      The activity of the HIF-1 complex is primarily controlled by levels of the alpha
      subunit and a series of mechanisms exist to control activation of the HIF-1
      pathway. HIF-1alpha is over-expressed in a large number of human tumors and its
      over-expression correlates with poor prognosis and treatment failure. HIF-1 is
      therefore an important target for cancer chemotherapy. This review summarizes the
      literature surrounding the control of HIF-1, its role in cancer and potential
      drugs to target the pathway for cancer therapy.

PMID- 14683499
TI  - Nitric oxide-releasing non steroidal anti-inflammatory drugs: a new generation of
      anti-tumoral molecules.
AB  - Colorectal cancer is the second most common cause of cancer-related mortality in
      the west. The high incidence and mortality make effective prevention an important
      public-health and economic issue. The regular intake of aspirin and other non
      steroidal anti-inflammatory drugs (NSAIDs) has been associated with decreased
      incidence of certain types of cancer particularly those with an inflammatory
      component, and then are among the few agents known to be chemopreventive. Nitric
      oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are new
      chemical entities obtained by adding a nitric oxide-releasing moiety to classical
      molecules. This new class of molecules has been demonstrated to be much more safe
      than NSAIDs due to their ability to reduce gastric toxicity. They could therefore
      represent an alternative to classical NSAIDs treatment. In this review, we
      sumarise the recent findings in the mechanisms and pathways involved in the
      antitumoral effects of both NSAIDs and NO-NSAIDs as well as the clinical trials
      performed with these compounds.

PMID- 14683500
TI  - Emerging role of endoglin (CD105) as a marker of angiogenesis with clinical
      potential in human malignancies.
AB  - Angiogenesis is crucial for tumor development and progression, and
      antiangiogenetic therapy represents a promising approach for cancer treatment.
      Thus, the in-depth understanding of the molecular mechanism(s) regulating
      angiogenesis, together with the characterization of molecules expressed by
      endothelial cells and involved in distinct steps of the angiogenetic process,
      will greatly improve the design of new and more effective therapeutic strategies
      in human malignancies. Endoglin (CD105), a cell membrane glycoprotein
      predominantly expressed on cellular lineages within the vascular system, and over
      expressed on proliferating endothelial cells, is involved in blood vessels
      development and represents a powerful marker of neovascularization. CD105 binds
      several factors of the Transforming Growth Factor (TGF)-beta superfamily, a
      pleiotropic cytokine that regulates different cellular functions including
      proliferation, differentiation and migration. In human malignancies of different
      histotype, CD105 is highly expressed on endothelial cells of both peri- and intra
      tumoral blood vessels, while it is weakly expressed or absent on neoplastic
      cells. This unique tissue distribution strongly suggests for a prognostic,
      diagnostic and therapeutic potential of CD105 in neoplastic diseases. In this
      review we will summarize the structural and functional features of CD105, as well
      as its tissue distribution in normal and neoplastic tissues. Furthermore, the
      practical implications of CD105 in human malignancies will also be discussed.

PMID- 14683501
TI  - Thomsen-friedenreich disaccharide immunogenicity.
AB  - Mucin-type O-glycans are upregulated and aberrantly glycosylated in many
      carcinomas. O-glycan Core 1 (Galbeta1-3GalNAcalpha-O-), also called Thomsen
      Friedenreich disaccharide, is a cryptic structure overexpressed in cancer cells
      through modification of its glycosyltransferase profile. This molecule is a
      useful model for study of carbohydrate immunogenicity as well as a candidate for
      active specific immunotherapy of cancer patients. Several strategies are
      discussed for enhancing immune response to a particular region of carbohydrate:
      carbohydrate-protein conjugation, linkers, synthetic clustered sugars, chemical
      modifications, peptide/protein mimetics, and molecular rotation.

PMID- 14683502
TI  - Metabolic biomarker and kinase drug target discovery in cancer using stable
      isotope-based dynamic metabolic profiling (SIDMAP).
AB  - Tumor cells respond to growth signals by the activation of protein kinases,
      altered gene expression and significant modifications in substrate flow and re
      distribution among biosynthetic pathways. This results in a proliferating
      phenotype with altered cellular function. These transformed cells exhibit unique
      anabolic characteristics, which includes increased and preferential utilization
      of glucose through the non-oxidative steps of the pentose cycle for nucleic acid
      synthesis but limited de novo fatty acid synthesis and TCA cycle glucose
      oxidation. This primarily non-oxidative anabolic profile reflects an
      undifferentiated highly proliferative aneuploid cell phenotype and serves as a
      reliable metabolic biomarker to determine cell proliferation rate and the level
      of cell transformation/differentiation in response to drug treatment. Novel drugs
      effective in particular cancers exert their anti-proliferative effects by
      inducing significant reversions of a few specific non-oxidative anabolic
      pathways. Here we present evidence that cell transformation of various mechanisms
      is sustained by a unique disproportional substrate distribution between the two
      branches of the pentose cycle for nucleic acid synthesis, glycolysis and the TCA
      cycle for fatty acid synthesis and glucose oxidation. This can be demonstrated by
      the broad labeling and unique specificity of [1,2-(13)C(2)]glucose to trace a
      large number of metabolites in the metabolome. Stable isotope-based dynamic
      metabolic profiles (SIDMAP) serve the drug discovery process by providing a
      powerful new tool that integrates the metabolome into a functional genomics
      approach to developing new drugs. It can be used in screening kinases and their
      metabolic targets, which can therefore be more efficiently characterized,
      speeding up and improving drug testing, approval and labeling processes by saving
      trial and error type study costs in drug testing.

PMID- 14683503
TI  - Cyclooxygenase inhibition and mechanisms of colorectal cancer prevention.
AB  - Colorectal cancer is a leading cause of cancer death throughout the world. The
      high prevalence and mortality associated with colon cancer make effective
      prevention and treatment an important public health and economic concern. Among
      the few agents known to inhibit colorectal tumorigenesis are the nonsteroidal
      anti-inflammatory drugs or NSAIDs, as well as newer agents such as celecoxib and
      rofecoxib. Both epidemiologic studies and investigations with animals show that
      these compounds possess marked anti-colorectal cancer properties. NSAIDS are
      widely known to be inhibitors of the cyclooxygenase (COX) enzymes, and it is
      thought that the chemopreventive effects of NSAIDs are at least in part due to
      this ability to inhibit COX. More recent studies, however, have suggested that
      NSAIDs may also exert anti-cancer effects through mechanisms independent of COX
      inhibition. COX-dependent and COX-independent mechanisms are not mutually
      exclusive and it is likely that both are involved in the biological activity of
      NSAIDs.

PMID- 14683504
TI  - Solid-phase synthesis of structurally diverse scaffolded peptides for the mimicry
      of discontinuous protein binding sites.
AB  - Scaffolded peptides, in which fragments of the sequence are presented through a
      molecular scaffold in a discontinuous and nonlinear fashion, are promising
      candidates for the mimicry of discontinuous protein binding sites. Twelve
      scaffold molecules based on cyclic peptides with ring sizes ranging from 13 to 30
      were generated. Up to three different peptide fragments were attached to the
      scaffolds in a site-selective manner, yielding scaffolded peptides in excellent
      purities, as documented by MS, HPLC, and 2D (1)H NMR spectroscopy data.

PMID- 14683505
TI  - Structural investigation of proapoptotic peptide by CD and NMR spectroscopy.
AB  - We have performed a systematic investigation of the structural features of the
      peptides Int (a sequence able to cross cell membranes) and Int-H1(S6A,F8A) (which
      shows interesting antitumoral properties). After screening in aqueous solution at
      different ionic strength and pH values, we analyzed the structures of the
      peptides in different water/trifluoroethanol mixtures by Circular Dichroism and
      Nuclear Magnetic Resonance techniques.

PMID- 14683506
TI  - Crystal structure of hemoglobin from the maned wolf (Chrysocyon brachyurus) using
      synchrotron radiation.
AB  - Crystal structure of hemoglobin isolated from the Brazilian maned wolf
      (Chrysocyon brachyurus) was determined using standard molecular replacement
      technique and refined using maximum-likelihood and simulated annealing protocols
      to 1.87A resolution. Structural and functional comparisons between hemoglobins
      from the Chrysocyon brachyurus and Homo sapiens are discussed, in order to
      provide further insights in the comparative biochemistry of vertebrate
      hemoglobins.

PMID- 14683507
TI  - Kinetics and thermodynamics of the native and mutated extracellular endo
      glucanases from Cellulomonas biazotea.
AB  - The mutation had dramatic effect on the kinetic and thermodynamic parameters
      inferring thermostability of endo-glucanase from Cellulomonas biazotea mutant 51
      SM(r). The denaturation activation energies of native and mutated enzymes were
      73.3 and 68.8 kJ/mol respectively. They showed compensation effect at 55 degrees
      C. Both enthalpy and entropy values of irreversible thermal inactivation for
      mutated enzyme were decreased suggesting that the mutation partly stabilized the
      enzyme.

PMID- 14683508
TI  - Analysis of fibril formation of amyloid-beta-protein by stretched exponential
      function.
AB  - Kinetic behavior of aggregation of amyloid-beta-protein (Abeta) is represented by
      a stretched exponential function, F=A[1-exp(-Bt(n))]. Differences in temperature
      dependence of A, B and n are studied for Abeta 1-40 and Abeta 1-42. As the
      temperature is lowered, parameter A is increased, parameter B is decreased and
      parameter n is increased in Abeta 1-40, while these parameters are less sensitive
      to temperature in a more hydrophobic protein Abeta 1-42. ln B is a linear
      function of n, which is shown by ln B = -6.34n + 3.69.

PMID- 14683509
TI  - Salting-in effects offset MgCL(2)-induced refolding of nucleoside diphosphate
      kinase.
AB  - Previously we reported that halobacterial nucleoside diphosphate kinase can be
      refolded in the presence of concentrated trimethylamine N-oxide (TMAO) as well as
      NaCl, indicating that enhancement of compact structure formation by TMAO is
      sufficient for folding. Here we showed that the refolding effect of MgCl(2) is
      maximal at 1 M and declines to zero at 2 M, indicating that charge shielding
      effect of MgCl(2) is offset by its salting-in effect.

PMID- 14683510
TI  - Cloning and expression of a new rat procarboxypeptidase B gene in Escherichia
      coli and purification of recombination carboxypeptidase B.
AB  - A new coding sequence of the procarboxypeptidase B gene was obtained from SD rat
      fresh pancreas by RT-PCR and highly expressed in Escherichia coli in inclusion
      bodies. The folded procarboxypeptidase B was subjected to trypsin enzymatic
      cleavage to produce active carboxypeptidase B, subsequently, carboxypeptidase B
      was effectively purified with anion exchange chromatography DEAE-FF and
      hydrophobic interaction chromatography Octyl FF, as a result, 40 mg
      carboxypeptidase B per litre cell culture with specific activity 7.42 u/mg was
      achieved. Further research showed that the obtained recombinant carboxypeptidase
      B could substitute carboxypeptidase B isolated from pancreas.

PMID- 14683511
TI  - A non-intuitive design of a cyclic decapeptide library with unique backbone
      structural features.
AB  - An analysis of hydrogen bonding patterns of cyclic decapeptide (CDP) beta-sheet
      structures has resulted in a 'non-intuitive' design of cyclic decapeptides
      wherein their beta-turns and residue positions can be fixed by choosing 2 of the
      10 residues, i.e. positions i and i+4, to be Prolines or N-substituted residues.
      This sequence relationship between the two Pro or N-substituted residues is shown
      to uniquely define the conformation of the CDP. Furthermore, this design of the 2
      beta-turn, beta-sheet CDP structure is expected to be characterised by residues
      disposed in an exclusive fashion in which four residues are on one side of the
      ring, two on the other and the four corner residues in the beta-turn are in the
      plane of the ring. This opens up the possibility of fine-tuning the four residues
      facing one way and /or the two residues facing the other way such that a library
      containing a myriad of chemically diverse systems could be obtained. The design
      process along with the molecular modelling of specific CDP-s and the building of
      a CDP library are discussed in detail.

PMID- 14683512
TI  - The site-directed mutagenesis of gastrodia anti-fungal protein mannose-binding
      sites and its expression in Escherichia coli.
AB  - Gastrodia anti-fungal protein (GAFP) displays strong inhibitory activity against
      certain fungal pathogens. Five GAFP analogues with different mutations at mannose
      binding sites and the wild-type one were expressed and purified in Escherichia
      coli. The inhibitory analysis of the purified various GAFPs against the growth of
      Trichoderma viride indicates that single amino acid mutated-type GAFPs have
      inhibitory activity, but its activity is much less than the wild-type one. The
      double and triplicate amino acids mutated GAFPs have very low inhibitory
      activity. For the first time it was proved that GAFP mannose-binding sites play
      key role in anti-fungi process.

PMID- 14683513
TI  - Seed lectin from pisum arvense: isolation, biochemical characterization and amino
      acid sequence.
AB  - A glucose/mannose lectin was purified by affinity chromatography from Pisum
      arvense seeds (PAL) and the 50 kDa molecular mass in solution determined by size
      exclusion chromatography. SDS-PAGE and electrospray ionization mass spectrometry
      showed two distinct polypeptide chains: alpha (Mr. 5591 Da) and beta (19986 Da).
      The lectin was extensively characterized in terms of its biochemical and
      biological aspects. The amino acid sequence was established by Edman degradation
      of overlapping peptides. PAL in solution behaves as a dimer and has its monomeric
      structure formed by two distinct polypeptide chains named alpha (Mr. 5591 Da) and
      beta (19986 Da) by Electrospray ionization (ESI) mass spectrometry. PAL possesses
      identical amino acid sequences to that of pea seed lectin but undoubtedly does
      not exhibit sequence heterogeneity. It is discussed that P. arvense should be
      considered as a synonym of P. sativum. Furthermore, like pea lectin, PAL
      discriminates biantennary fucosylated glycan, determined by surface plasmon
      resonance.

PMID- 14683514
TI  - Immobilization of lipases and assay in continuous fixed bed reactor.
AB  - Lipases are versatile enzymes regarding the range of reactions they catalyse and
      substrates on which they act. They are as well important as catalyst in organic
      synthesis. Their immobilization on appropriate supports confer them greater
      stability besides the possibility of operating in continuous reactors. In order
      to explore these abilities, the reactions involving hydrolysis of p-nitrophenyl
      acetate (PNPA) and transesterification of PNPA with n-butanol were chosen.
      Lipases from two different sources were assayed, namely: microbial (Candida
      rugosa, CRL, Sigma Type VII) and pancreatic (PPL, Sigma, Type II). Two
      immobilization methods were also used, namely: 1). adsorption, using as support
      the following silica derivatives (150-300 microm e 450micro): phenyl, epoxy,
      amino and without derivation, and 2). covalent binding, using glutaraldehyde as
      binding agent and silica amino as support. This later method led to better
      results. Hydrolytic activity was 6.1 U/g(support) for CRL and 0.97 U/g(support)
      for PPL, and of transesterification, 2,8 U/g(support) for CRL and 1,9
      U/g(support) for PPL. Stability of the immobilized enzyme as a function of
      temperature was evaluated for CRL at 40 degrees C and 50 degrees C and for PPL at
      32 degrees C and 40 degrees C. The assays were initially carried out batchwise,
      both for soluble and immobilized enzymes, aiming to the obtention of parameters
      for the continuous reactor. Lipases immobilized by covalent binding were used in
      the assays of operational stability in continuous reactors. For PPL in aqueous
      medium, at 32 degrees C, and CRL in organic medium at 40 degrees C, both
      operating continuously, no significant loss of activity was detected along the
      analysis period of 17 days. In the case of CRL in aqueous medium at 40 degrees C
      there was a loss of activity around 40% after 18 days. For PPL in organic medium
      at 40 degrees C the loss was 33% after 20 days. Comparing both sources with each
      other, very different results were obtained. Higher activity was found for CRL,
      both for hydrolysis and for transesterification reactions, with higher stability
      in organic medium. PPL showed lower activity as well as higher stability in
      aqueous medium. The immobilization method by covalent binding showed to be the
      most appropriate. Immobilized lipases are therefore relatively stable both in
      aqueous and organic medium.

PMID- 14683515
TI  - Vitamin D analogs as modulators of vitamin D receptor action.
AB  - The natural calcium-regulating hormone 1alpha,25-dihydroxyvitamin D(3) (1,25D(3))
      is a secosteroid that offers organic chemists many sites for modifying structural
      and/or functional groups. Such modifications alter the chemistry,
      stereochemistry, and biological properties of the natural hormone. The resulting
      deltanoids (vitamin D analogs) have been used in the past two decades as
      molecular probes to investigate structure-function relationships based on their
      interactions with proteins that regulate deltanoid biostability (catabolic
      enzymes of the vitamin D endocrine system and vitamin D binding protein) and
      deltanoid transduction of biological activities (nuclear and membrane receptors).
      In this review we will focus on structural modifications of 1,25D(3) that
      selectively modulate the nuclear vitamin D receptor (VDR). We will discuss the
      structural requirements and modifications that create analogs with greater
      potency and efficacy than the natural hormone (superagonists). We will also
      identify the structural features of an emerging group of noncalcemic selective
      agonists and describe the pharmacokinetic properties and VDR-mediated actions
      that promote their tissue- and gene-selective responses. In addition, we will
      speculate on the possible structural requirements for vitamin D antagonists. We
      will also examine the evidence from studies in cell-free systems, in culture and
      in vivo that explain the mechanisms for the distinct actions of each group of
      analogs, with special emphasis on the relationship between their mode of
      interaction with the VDR and the molecular and cellular outcome of these
      interactions. Finally, we will describe the current and potential use of these
      selective modulators of the VDR for treatment of human diseases such as
      osteoporosis, cancer, and secondary hyperparathyroidism.

PMID- 14683516
TI  - Structure-activity relationship of nuclear receptor-ligand interactions.
AB  - Small molecules such as retinoids, steroid hormones, fatty acids, cholesterol
      metabolites, or xenobiotics are involved in the regulation of numerous
      physiological and patho-physiological processes by binding to and controlling the
      activity of members of the nuclear receptor (NR) superfamily of transcription
      factors. In addition to natural ligands, synthetic agonists or antagonists have
      been identified that in some cases specifically target NR isotypes, or elicit
      tissue-, signaling pathway-, or promoter-selective transcriptional responses. For
      these ligands the term "selective NR modulators" (SNRMs) has been introduced.
      Structure determination of apo- and holo-NR ligand-binding domains (LBDs)--some
      of them complexed to small coactivator or corepressor fragments--revealed the
      major principles of ligand-dependent NR action and determinants of (isotype-)
      selective ligand binding. These studies also stimulated the interpretation of
      tissue-specific effects of SNRMs on wild-type or mutant receptors. In contrast to
      the increasing knowledge on the structure-activity relationship of NRs with known
      SNRMs, rather basic questions remain about the regulation of orphan NRs (for
      which no ligands are known) or "adopted" orphan NRs (for which only recently
      ligands were identified). Several crystal structures of orphan NR LBDs uncovered
      unexpected properties, contributed to the understanding of orphan NR function,
      and may in the future permit the identification or design of ligands. This review
      will (i) focus on the current understanding of the structure-activity
      relationship of NR-ligand interactions, (ii) discuss recent advances in the field
      of "orphan" NR crystallography, and (iii) outline future challenges in NR
      structural biology.

PMID- 14683517
TI  - Selective thyroid hormone receptor modulators.
AB  - Thyroid hormone regulates many important processes in vertebrates. Analysis of
      the symptoms that accompany hypo- and hyperthyroidism, the most common disorders
      of the thyroid, suggests that there are certain desirable biological effects
      brought about by an excess or deficiency of thyroid hormone, and that selective
      thyroid hormone receptor modulators (STRMs) would be potentially useful
      therapeutic agents. This review will provide an introduction to thyroid hormone
      biology, and will discuss the chemistry and pharmacology of the first generation
      STRMs.

PMID- 14683518
TI  - The pursuit of differentiated ligands for the glucocorticoid receptor.
AB  - Glucocorticoids have a pervasive role in human health and physiology. The
      endogenous members of this family are involved in a breadth of endocrine
      functions including metabolism of lipids, carbohydrates and proteins, stress
      response, fluid and electrolyte balance, as well as maintenance of immunological,
      renal and skeletal homeostasis. The predominant mode of action of glucocorticoids
      involves regulation of gene expression via the glucocorticoid receptor (GR).
      Synthetic glucocorticoids have long been the standard for the treatment of
      inflammatory and immune disorders, yet the benefits of classic steroids such as
      dexamethasone and prednisolone are accompanied by well-characterized potentiation
      of homeostatic endocrine functions, leading to the side effects associated with
      prolonged treatment. In recent campaigns for safer analogs, compounds have been
      sought which differentiate functional repression of existing transcription
      factors such as AP-1 and NFkappaB from GR-mediated transcriptional activation
      arising from binding at glucocorticoid-receptor response elements (GREs). Such
      differentiated ligands would provide the desired immunoregulatory actions without
      the endogenous changes in gene expression associated with undifferentiated
      steroids. We detail the methods for the evaluation of selective GR modulators and
      describe the evolution of new compounds where varying degrees of selectivity have
      been reported.

PMID- 14683519
TI  - Orphan nuclear receptor modulators.
AB  - Nuclear hormone receptors are ligand-activated transcription factors that
      regulate gene expression and play a critical role in endocrine signaling. Orphan
      nuclear receptors belong to this gene super-family but their target genes and
      physiological function have not been completely elucidated. In recent years, the
      identification of natural ligands for these orphan receptors, their expression
      pattern in different tissues and studies with knock-out animals has delineated
      distinct regulatory functions for these proteins. The orphans belonging to the
      PPAR, LXR and FXR family function as lipid and bile-acid sensors while PXR and
      CAR function as xenobiotic sensors. This review will describe the discovery of
      natural and synthetic ligands for a number of these orphan receptors (excluding
      the PPARs) and the identification and characterization of novel signaling
      pathways and new hormone response systems linked to these targets. Small-molecule
      modulators of LXR and FXR control key genes involved in cholesterol and lipid
      metabolism. PXR is a highly promiscuous xenosensor that responds to xenobiotic
      ligands (antibiotics, statins, glucocorticoids) and induces the Cyp3A gene,
      thereby playing a role in hepatoprotection and bile acid metabolism. A related
      receptor from the gene subfamily, CAR, displays high ligand selectivity and
      modulation of its activity in humans may significantly alter metabolism of drugs
      and other xenobiotics. The role of the ER relatives, the ERRs will become more
      apparent as ligands are identified and linked to target genes and physiological
      function. These targets offer multiple opportunities for therapeutic intervention
      with small-molecule drugs, in diseases related to neuronal function,
      inflammation, lipid homeostasis, metabolic function and cancer.

PMID- 14683520
TI  - PPAR ligands for metabolic disorders.
AB  - As master regulators of lipid metabolism the peroxisome proliferator activated
      receptor (PPAR) family controls a wide variety of cellular processes, and thus it
      is not surprising that a large effort has focussed on discovering agents to
      pharmacologically modulate activity of these receptors. Early generation PPAR
      ligands, such as the fibrates and the thiazolidinediones (TZDs), were discovered
      empirically through an in vivo structure activity relationship exercise, whereas
      currently PPAR ligands are more often identified through target based structural
      design using cloned and expressed receptors. Regardless of how they were
      discovered, the development and clinical use of PPAR ligands throughout the last
      decade has greatly advanced understanding of the physiological function and
      therapeutic value of modulating these receptors. This review will briefly examine
      the PPAR family and then outline in greater detail select PPAR ligands indicated
      for the treatment of metabolic disorders.

PMID- 14683521
TI  - Estrogen receptor modulators: relationships of ligand structure, receptor
      affinity and functional activity.
AB  - The estrogen receptor is a regulator of a wide range of physiological functions,
      including the female reproductive system, in addition to bone, cardiovascular and
      CNS function. ER ligands have been approved for the treatment of menopausal
      symptoms, breast cancer and osteoporosis, however the search continues for new
      modulators of ER function with improved properties. Progress in medicinal
      chemistry programs has resulted in the identification of structurally diverse
      molecules with unique biological properties. Recent advances in the design and
      synthesis of these non-steroidal and steroidal estrogen receptor ligands is
      reviewed. The relationship between the structural features of the ligand and
      receptor function is also discussed.

PMID- 14683522
TI  - Effects of a Mediterranean-inspired diet on blood lipids, vascular function and
      oxidative stress in healthy subjects.
AB  - Mediterranean-inspired diets have been shown to decrease cholesterol levels in
      patients with hypercholesterolaemia, who frequently exhibit endothelial
      dysfunction. The aims of the present study are to improve endothelial function by
      dietary intervention in healthy subjects with lipid levels representative of a
      Western population. Twenty-two healthy subjects (mean total cholesterol, 5.6
      mmol/l) were given a Mediterranean-inspired diet rich in omega-3 fatty acids and
      sterol esters, but low in saturated fat, or an ordinary Swedish diet, for 4 weeks
      in a randomized cross-over study. The composition of the diets were: in the
      Swedish diet, 2090 kcal (where 1 kcal=4.184 kJ; 48% of energy from carbohydrate,
      15% from protein and 36% from fat) and 19 g of fibre; in the Mediterranean
      inspired diet, 1869 kcal (48% of energy from carbohydrate, 16% from protein, 34%
      from fat) and 40 g of fibre. After each dietary period, fasting blood lipids,
      insulin and glucose levels, as well as apo B (apolipoprotein B) and LDL (low
      density lipoprotein) particle size, were analysed. Endothelial-dependent and 
      independent vasodilation was measured invasively by venous occlusion
      plethysmography, and arterial distensibility was assessed by echocardiography
      tracking. Fibrinolytic capacity across the forearm, as well as oxidative stress
      measured through urinary F(2)-isoprostane, were evaluated. Total, LDL- and apo B
      cholesterol and triacylglycerol (triglyceride) concentrations were decreased by
      17%, 22%, 16% and 17% respectively, after the Mediterranean-inspired diet
      compared with the Swedish diet ( P <0.05 for all). However, no differences in
      plasma concentrations of insulin and glucose and LDL particle size, endothelial
      function, arterial distensibility, fibrinolytic capacity or oxidative stress were
      detected. Treatment for 4 weeks with a Mediterranean-inspired diet decreased
      blood lipids in healthy individuals with a low-risk profile for cardiovascular
      disease. This beneficial effect was not mirrored in vascular function or
      oxidative stress evaluation.

PMID- 14683523
TI  - Thrombospondin-1 mediates distal tubule hypertrophy induced by glycated albumin.
AB  - Diabetic nephropathy is characterized by early hypertrophy in both glomerular and
      tubuloepithelial elements. However, no studies to date have established a direct
      causal link between hyperglycaemia and renal hypertrophy. Our previous studies
      have found that high glucose does not induce cellular hypertrophy or expression
      of TGF-beta1 (transforming growth factor-beta1) in distal renal tubule cells
      [Yang, Guh, Yang, Lai, Tsai, Hung, Chang and Chuang (1998) J. Am. Soc. Nephrol.
      9, 182-193]. In the present study, we used AGEs (advanced glycation end-products)
      to mimic long-term hyperglycaemia. Similar to glucose, AGEs did not induce TGF
      beta1 mRNA in distal renal tubule cells [MDCK (Madin-Darby canine kidney) cells];
      however, TGF-beta1 bioactivity was increased significantly. This result indicated
      post-translational regulation. Since TSP-1 (thrombospondin-1) has been
      demonstrated to activate latent TGF-beta1 in a variety of systems, the following
      experiments were performed. We found that AGEs dose-dependently increased both
      intracellular and extracellular levels of TSP-1. Purified TSP-1, like AGEs,
      increased the cellular protein content. Furthermore, anti-TSP-1 neutralizing
      antibodies attenuated the AGE-induced increase in TGF-beta1 bioactivity and
      hypertrophy. Thus TSP-1 might mediate AGE-induced distal renal tubule
      hypertrophy. In addition, we observed several putative transcription factor
      binding sites in the TSP-1 promoter, including those for AP-1 (activator protein
      1), CREB (cAMP response element binding protein), NF-kappaB (nuclear factor
      kappaB), SRF (serum response factor) and HSF (heat-shock factor), by sequence
      mapping. We used an enhancer assay to screen possible transcription factors
      involved. We showed that AP-1 and CREB were specifically induced by AGEs;
      furthermore, TFD (transcription factor decoy) for AP-1 could attenuate the AGE
      induced increases in TSP-1 levels and cellular hypertrophy. Thus regulation of
      TSP-1 might be critical for hyperglycaemic distal tubule hypertrophy.
      Furthermore, TSP-1 TFD might be a potential approach to ameliorate diabetic renal
      hypertrophy.

PMID- 14683524
TI  - Alteration of the bioenergetic phenotype of mitochondria is a hallmark of breast,
      gastric, lung and oesophageal cancer.
AB  - Recent findings indicate that the expression of the beta-catalytic subunit of the
      mitochondrial H+-ATP synthase (beta-F1-ATPase) is depressed in liver, kidney and
      colon carcinomas, providing further a bioenergetic signature of cancer that is
      associated with patient survival. In the present study, we performed an analysis
      of mitochondrial and glycolytic protein markers in breast, gastric and prostate
      adenocarcinomas, and in squamous oesophageal and lung carcinomas. The expression
      of mitochondrial and glycolytic markers varied significantly in these carcinomas,
      when compared with paired normal tissues, with the exception of prostate cancer.
      Overall, the relative expression of beta-F1-ATPase was significantly reduced in
      breast and gastric adenocarcinomas, as well as in squamous oesophageal and lung
      carcinomas, strongly suggesting that alteration of the bioenergetic function of
      mitochondria is a hallmark of these types of cancer.

PMID- 14683525
TI  - Immobilization of Aspergillus niger tannase by microencapsulation and its kinetic
      characteristics.
AB  - Tannase from Aspergillus niger was microcapsulated with a coacervate calcium
      alginate membrane surrounding a liquid core. The activity yield was 36.8% under
      the optimum conditions of immobilization, namely 6 g/litre sodium alginate and
      0.18 M CaCl(2). The optimum pH and temperature for free and immobilized tannase
      were 5.0 and 30 degrees C, and 6.0 and 40 degrees C, respectively. The pH
      stability, as well as thermal stability, was improved significantly after
      microencapsulation. K(m) values for the free and immobilized enzyme were 0.011
      and 0.041 microM respectively. V(max) values changed from 416 to 131 micromol x
      min(-1) x mg(-1) upon immobilization. The kinetic parameters for free and
      immobilized tannase were also determined. The immobilized tannase was stable
      enough to be used for up to 15 runs. These kinetic characteristics of the
      immobilized tannase show more promise for industrial application than those of
      the free enzyme.

PMID- 14683526
TI  - Ill or just old? Towards a conceptual framework of the relation between ageing
      and disease.
AB  - BACKGROUND: Is this person ill or just old? This question reflects the pondering
      mind of a doctor while interpreting the complaints of an elderly person who seeks
      his help. Many doctors think that ageing is a non-disease. Accordingly, various
      attempts have been undertaken to separate pathological ageing from normal ageing.
      However, the existence of a normal ageing process distinct from the pathological
      processes causing disease later in life can be questioned. DISCUSSION: Ageing is
      the accumulation of damage to somatic cells, leading to cellular dysfunction, and
      culminates in organ dysfunction and an increased vulnerability to death.
      Analogously, chronic diseases initiate early in life and their development is
      slow before they become clinically apparent and culminate in disability or death.
      The definition of disease is also subject to current opinions and scientific
      understanding and usually, it is an act of individual creativity when physical
      changes are recognised as symptoms of a new disease. New diseases, however, are
      only rarely really new. Most new diseases have gone undiagnosed because their
      signs and symptoms escaped recognition or were interpreted otherwise. Many
      physical changes in the elderly that are not yet recognised as a disease are thus
      ascribed to normal ageing. Therefore, the distinction between normal ageing and
      disease late in life seems in large part arbitrary. SUMMARY: We think that normal
      ageing cannot be separated from pathological processes causing disease later in
      life, and we propose that the distinction is avoided.

PMID- 14683527
TI  - Construction of two genetic linkage maps in cultivated tetraploid alfalfa
      (Medicago sativa) using microsatellite and AFLP markers.
AB  - BACKGROUND: Alfalfa (Medicago sativa) is a major forage crop. The genetic
      progress is slow in this legume species because of its autotetraploidy and
      allogamy. The genetic structure of this species makes the construction of genetic
      maps difficult. To reach this objective, and to be able to detect QTLs in
      segregating populations, we used the available codominant microsatellite markers
      (SSRs), most of them identified in the model legume Medicago truncatula from EST
      database. A genetic map was constructed with AFLP and SSR markers using specific
      mapping procedures for autotetraploids. The tetrasomic inheritance was analysed
      in an alfalfa mapping population. RESULTS: We have demonstrated that 80% of
      primer pairs defined on each side of SSR motifs in M. truncatula EST database
      amplify with the alfalfa DNA. Using a F1 mapping population of 168 individuals
      produced from the cross of 2 heterozygous parental plants from Magali and
      Mercedes cultivars, we obtained 599 AFLP markers and 107 SSR loci. All but 3 SSR
      loci showed a clear tetrasomic inheritance. For most of the SSR loci, the double
      reduction was not significant. For the other loci no specific genotypes were
      produced, so the significant double-reduction could arise from segregation
      distortion. For each parent, the genetic map contained 8 groups of four
      homologous chromosomes. The lengths of the maps were 2649 and 3045 cM, with an
      average distance of 7.6 and 9.0 cM between markers, for Magali and Mercedes
      parents, respectively. Using only the SSR markers, we built a composite map
      covering 709 cM. CONCLUSIONS: Compared to diploid alfalfa genetic maps, our maps
      cover about 88-100% of the genome and are close to saturation. The inheritance of
      the codominant markers (SSR) and the pattern of linkage repulsions between
      markers within each homology group are consistent with the hypothesis of a
      tetrasomic meiosis in alfalfa. Except for 2 out of 107 SSR markers, we found a
      similar order of markers on the chromosomes between the tetraploid alfalfa and M.
      truncatula genomes indicating a high level of colinearity between these two
      species. These maps will be a valuable tool for alfalfa breeding and are being
      used to locate QTLs.

PMID- 14683528
TI  - Different cDNA microarray patterns of gene expression reflecting changes during
      metastatic progression in adenoid cystic carcinoma.
AB  - BACKGROUND: The metastatic ability of tumor cells is determined by level of
      expression of specific genes that may be identified with the aid of cDNA
      microarray containing thousands of genes and can be used to establish the
      expression profile of disease related genes in complex biological system.
      MATERIALS AND METHODS: Salivary adenoid cystic carcinoma cell line and its high
      metastases adenoid cystic carcinoma clone were used as model systems to reveal
      the gene expression alteration related to metastasis mechanism by cDNA microarray
      analysis. The correlation of metastatic phenotypic changes and expression levels
      of 4 selected genes (encoding CD98, L6, RPL29, and TSH) were further validated by
      using RT-PCR analysis of human tumor specimens from primary adenoid cystic
      carcinoma and corresponding metastasis lymph nodes. RESULTS: Of the 7,675 clones
      of known genes and expressed sequence tags (ESTs) that were analyzed, 30 showed
      significantly different (minimum 3 fold) expression levels in two cell lines. Out
      of 30 genes found differentially expressed, 18 were up regulated (with ratio more
      than 3) and 12 down regulated (with ratio less than 1/3). CONCLUSION: Some of
      these genes are known to be involved in human tumor antigen, immune surveillance,
      adhesion, cell signaling pathway and growth control. It is suggested that the
      microarray in combination with a relevant analysis facilitates rapid and
      simultaneous identification of multiple genes of interests and in this study it
      provided a profound clue to screen candidate targets for early diagnosis and
      intervention.

PMID- 14683529
TI  - Vascular endothelial growth factor (VEGF) fails to improve blood flow and to
      promote collateralization in a diabetic mouse ischemic hindlimb model.
AB  - BACKGROUND: Angiogenic therapy with vascular endothelial growth factor (VEGF) has
      been proposed as a treatment paradigm for patients suffering from an
      insufficiency of collateral vessels. Diabetes is associated with increase in the
      production of VEGF and therefore additional VEGF may not be beneficial.
      Accordingly, we sought to determine the efficacy of VEGF therapy to augment
      collateral formation and tissue perfusion in a diabetic mouse ischemic hindlimb
      model. METHODS: Diabetic and non-diabetic mice were studied in parallel for the
      efficacy of VEGF administration. Diabetes was induced with streptozotocin.
      Hindlimb ischemia was produced by severing the left iliac artery. An outlet tube
      from an osmotic infusion pump with placebo/500 micrograms of plasmid-DNA encoding
      VEGF was fenestrated and tunneled into the left quadriceps muscle. RESULTS: VEGF
      induced more rapid and complete restoration of blood flow in normal mice.
      However, in the setting of diabetes there was no difference between VEGF vs.
      placebo in the rate or adequacy of flow restoration. There was a significant
      increase in smooth muscle actin and Factor-VIII antigen densities in diabetic
      animals and in animals which received VEGF. CONCLUSIONS: Angiogenic therapy with
      VEGF in the setting of diabetes does not appear to have the beneficial effects
      seen in the absence of diabetes.

PMID- 14683530
TI  - PRIME--PRocess modelling in ImpleMEntation research: selecting a theoretical
      basis for interventions to change clinical practice.
AB  - BACKGROUND: Biomedical research constantly produces new findings but these are
      not routinely translated into health care practice. One way to address this
      problem is to develop effective interventions to translate research findings into
      practice. Currently a range of empirical interventions are available and
      systematic reviews of these have demonstrated that there is no single best
      intervention. This evidence base is difficult to use in routine settings because
      it cannot identify which intervention is most likely to be effective (or cost
      effective) in a particular situation. We need to establish a scientific rationale
      for interventions. As clinical practice is a form of human behaviour, theories of
      human behaviour that have proved useful in other similar settings may provide a
      basis for developing a scientific rationale for the choice of interventions to
      translate research findings into clinical practice. The objectives of the study
      are: to amplify and populate scientifically validated theories of behaviour with
      evidence from the experience of health professionals; to use this as a basis for
      developing predictive questionnaires using replicable methods; to identify which
      elements of the questionnaire (i.e., which theoretical constructs) predict
      clinical practice and distinguish between evidence compliant and non-compliant
      practice; and on the basis of these results, to identify variables (based on
      theoretical constructs) that might be prime targets for behaviour change
      interventions. METHODS: We will develop postal questionnaires measuring two
      motivational, three action and one stage theory to explore five behaviours with
      800 general medical and 600 general dental practitioners. We will collect data on
      performance for each of the behaviours. The relationships between predictor
      variables (theoretical constructs) and outcome measures (data on performance) in
      each survey will be assessed using multiple regression analysis and structural
      equation modelling. In the final phase of the project, the findings from all
      surveys will be analysed simultaneously adopting a random effects approach to
      investigate whether the relationships between predictor variables and outcome
      measures are modified by behaviour, professional group or geographical location.

PMID- 14683535
TI  - The Neuroform stent, the first microcatheter-delivered stent for use in the
      intracranial circulation.

PMID- 14683536
TI  - Preliminary experience using the Neuroform stent for the treatment of cerebral
      aneurysms.
AB  - INTRODUCTION: The Neuroform microstent-a flexible, self-expandable, microcatheter
      delivered, nitinol stent designed for the treatment of cerebral aneurysms-was
      recently approved for use in patients. We present the results of our initial
      experience in using the Neuroform stent to treat patients with cerebral
      aneurysms, with an emphasis on potential applications, technical aspects of
      deployment, and associated intra- and periprocedural complications. METHODS: The
      records of all patients treated with the Neuroform stent were entered
      prospectively into a database. We assessed the clinical history, indications for
      stent use, aneurysm dimensions, and technical details of the procedures,
      including any difficulties with stent placement and/or deployment, degree of
      aneurysm occlusion, and complications. RESULTS: During a 5-month period, 19
      patients with 22 aneurysms were treated with the Neuroform stent. Twenty-five
      stents were deployed. Five patients had multiple stents placed. Five patients had
      ruptured aneurysms at the time of treatment. The indications for use were broad
      necked aneurysms (n = 13; average neck length, 5.1 mm; average aneurysm size, 9
      mm), fusiform or dissecting aneurysms (n = 3), salvage and/or bailout (n = 1),
      and giant aneurysms (n = 2). Technical problems included difficulty in deploying
      the stent (n = 6), inability to deploy the stent (n = 1), stent displacement (n =
      2), inadvertent stent deployment (n = 1), and coil stretching (n = 1). Twenty-one
      of the 22 aneurysms were treated. Four aneurysms were stented without additional
      treatment, and 17 aneurysms were stented and coiled. Of the coiled aneurysms,
      complete or nearly complete (more than 95%) occlusion was achieved in 6
      aneurysms, and partial occlusion was achieved in 11. Two clinically significant
      adverse events occurred, both of which were sequelae of periprocedural
      thromboembolic complications. One patient died after thrombolysis was attempted.
      The other patient made an excellent functional recovery after undergoing
      successful thrombolysis of a thrombosed basilar artery stent. CONCLUSION: The
      Neuroform stent is a useful device for the treatment of patients with aneurysms
      that may not otherwise be amenable to endovascular therapy. In the majority of
      cases, the stent can be deployed accurately, even within the most tortuous
      segments of the cerebral vasculature. Although delivery and deployment may be
      technically challenging, clinically significant complications are uncommon.

PMID- 14683537
TI  - Age-dependent differences in short-term outcome after surgical or endovascular
      treatment of unruptured intracranial aneurysms in the United States, 1996-2000.
AB  - INTRODUCTION: Unruptured intracranial aneurysm patients are frequently eligible
      for both open surgery ("clipping") and endovascular repair ("coiling"). We
      compared short-term end points (mortality, discharge disposition, complications,
      length of stay, and charges) for clipping and coiling in a nationally
      representative discharge database. METHODS: We conducted a retrospective cohort
      study using Nationwide Inpatient Sample data from 1996 to 2000. Multivariate
      logistic regression analyses adjusted for age, sex, race, payer status,
      geographic region, presenting signs and symptoms, admission type and source,
      procedure timing, hospital caseload, and possible clustering of outcomes within
      hospitals. The results were confirmed by performing propensity score analysis.
      RESULTS: A total of 3498 patients had clipping, and 421 underwent coiling.
      Clipped patients were slightly younger (P < 0.001). Medical comorbidity was
      similar between the groups. More clipped patients had urgent or emergency
      admissions (P = 0.02). More coiling procedures were performed on hospital Day 1
      (P = 0.007). When only death and discharge to long-term care were counted as
      adverse outcomes, there was no significant difference between clipping and
      coiling. On the basis of a four-level discharge status outcome scale (dead, long
      term care, short-term rehabilitation, or discharge to home), coiled patients had
      a significantly better discharge disposition (odds ratio, 2.1; P < 0.001). With
      regard to patient age, most of the difference in discharge disposition was in
      patients older than 65 years of age. The degree of difference between treatments
      increased from 1996 to 2000. Neurological complications were coded twice as
      frequently in clipped patients as in coiled patients (P = 0.002). Length of stay
      was longer (5 d versus 2 d, P < 0.001) and charges were higher ($21,800 versus
      $13,200, P = 0.007) for clipped patients than for coiled patients. CONCLUSION:
      There was no significant difference in mortality rates or discharge to long-term
      facilities after clipping or coiling of unruptured aneurysms. When discharge to
      short-term rehabilitation was counted as an adverse event, coiled patients had
      significantly better outcomes than clipped patients at the time of hospital
      discharge, but most of the coiling advantage was concentrated in patients older
      than 65 years of age. Even in older patients, long-term end points-including long
      term functional status in patients discharged to rehabilitation and efficacy in
      preventing hemorrhage-will be critical in determining the best treatment option
      for patients with unruptured aneurysms.

PMID- 14683538
TI  - Incidence and early prognosis of aneurysmal subarachnoid hemorrhage in Kumamoto
      Prefecture, Japan.
AB  - OBJECTIVE: We analyzed the community incidence and early prognosis of first-ever
      aneurysmal subarachnoid hemorrhages (SAHs) to obtain the same prognostic
      information used by physicians and families in a defined geographic area in
      Japan. METHODS: During the 5-year period from January 1, 1996, to December 31,
      2000, 2115 patients were registered in the Data Bank for Cerebral Aneurysms of
      Kumamoto Prefecture, a defined area in Japan with a population of 1.86 million.
      Registration was based on a comprehensive referral system for SAH patients;
      computed tomographic scans were available for all patients, including those who
      were moribund or dead on arrival. We compared the treatment outcomes at 3 months
      after the first-ever SAH in surgically and conservatively treated patients.
      RESULTS: The age-adjusted annual incidence of SAH for men, women, and both sexes
      was 15.9, 26.6, and 21.6 per 100,000 person-years, respectively. In men, the
      incidence reached a plateau after age 40 years. In women, conversely, it rose
      after age 40 and peaked in the 9th decade of life. Of the 1634 surgically treated
      patients, 1153 (70.6%) had a favorable outcome; this was true for only 27 of 477
      (5.7%) conservatively treated patients. Four patients were lost to follow-up. The
      clinical outcome did not differ between patients treated by open surgery and
      those treated endovascularly. Approximately 30% of our patients were older than
      70 years at the time they experienced their first SAH. CONCLUSION: The incidence
      of SAH obtained in this study was similar to earlier Japanese reports and Finnish
      studies. The importance of managing elderly patients with cerebral aneurysms will
      continue to increase.

PMID- 14683539
TI  - Intraarterial thrombolytic therapy within 3 hours of the onset of stroke.
AB  - OBJECTIVE: The National Institute of Neurological Disorders and Stroke (NINDS)
      Recombinant Tissue Plasminogen Activator Stroke Study Group showed that
      recombinant tissue plasminogen activator (rt-PA) administered intravenously
      within 3 hours of the onset of ischemic stroke can improve clinical outcome.
      Intraarterial (IA) thrombolysis has been shown to offer advantages over
      intravenous (IV) thrombolysis, but experience with this type of therapy within 3
      hours of the onset of symptoms has not been reported previously. This study is
      the first retrospective analysis of a two-institution experience with IA
      thrombolysis within 3 hours of stroke onset. METHODS: A total of 36 patients with
      angiographically demonstrated occlusions were treated with urokinase or rt-PA
      within 3 hours of stroke onset. Outcome measures included the percentage of
      patients with no or minimal neurological disability at 30 to 90 days as measured
      by the modified Rankin Scale, percentage recanalization, incidence of symptomatic
      intracranial hemorrhage, and mortality rate. The results were compared with those
      of the NINDS rt-PA study. RESULTS: The median admission National Institutes of
      Health Stroke Scale score was 14. Fifty percent of treated patients had a
      modified Rankin Scale score of 0 or 1 indicating no or little disability at 1 to
      3 months compared with 39% of treated patients in the NINDS trial. Recanalization
      was 75%, symptomatic intracranial hemorrhage was 11% (versus 6.4% with IV rt-PA
      in the NINDS trial), and the mortality rate was 22% (versus 17% with IV rt-PA in
      the NINDS trial). CONCLUSION: The results suggest that IA thrombolysis
      administered within 3 hours of stroke onset is a feasible and viable alternative
      to IV rt-PA on the basis of improved clinical outcomes, high recanalization
      percentage, and comparable mortality rate and despite increased symptomatic
      intracranial hemorrhage. Whether IA thrombolysis is superior to IV therapy awaits
      further study.

PMID- 14683540
TI  - Anxiety and depression after spontaneous subarachnoid hemorrhage.
AB  - OBJECTIVE: Relatively little attention has been paid to emotional outcome after
      subarachnoid hemorrhage (SAH). This study assessed levels of anxiety and
      depression among SAH survivors and related these to clinical indices. METHODS:
      Seventy SAH patients from a consecutive series of neurosurgical admissions
      participated in semistructured assessments of functional outcome; 52 of the
      patients also returned standardized measures of emotional outcome. These data
      were compared with clinical indices collected during the initial hospital
      admission. RESULTS: Moderate to severe levels of anxiety were present in
      approximately 40% of patients 16 months after hemorrhage, with approximately 20%
      experiencing moderate to severe levels of depression. Although anxiety was more
      likely to be reported at interview by those with an SAH of Fisher Grade 4, the
      standardized measures of anxiety and depression were not associated with severity
      of hemorrhage or any other clinical variables. Both anxiety and depression were
      significantly associated with outcome indices such as return to work and
      engagement in social activities. CONCLUSION: Anxiety is a significant and lasting
      problem for approximately 40% of survivors of SAH. It is suggested that measures
      taken to prevent or treat such anxiety among survivors of SAH may serve to
      significantly improve functional outcome.

PMID- 14683541
TI  - Surgical resection and permanent brachytherapy for recurrent atypical and
      malignant meningioma.
AB  - OBJECTIVE: Recurrent atypical and malignant meningiomas are difficult to treat
      successfully. Chemotherapy to date has been unsuccessful, and radiosurgery is
      limited to smaller tumors. Reoperation alone provides limited tumor control and
      limited prolonged survival. The addition of brachytherapy at the time of
      operation is an option. Here, we report the results of our series of patients
      with recurrent malignant meningioma treated with resection and brachytherapy with
      permanent low-dose (125)I. METHODS: The charts of patients in our database with
      recurrent atypical and malignant meningiomas treated by surgical resection and
      permanent (125)I brachytherapy at the University of California, San Francisco,
      between 1988 and 2002 were selected for this study. Calculations of disease-free
      survival and overall survival curves were made by the Kaplan-Meier actuarial
      method. Univariate analysis between Kaplan-Meier curves was based on the log-rank
      statistic, with a significance level set at a value of P </= 0.05. RESULTS:
      Seventeen patients had recurrent malignant meningioma, and four had recurrent
      atypical meningioma. The median number of sources implanted after surgical
      resection was 30 (range, 4-112 sources), with a median total activity of 20 mCi
      (range, 3.3-85.9 mCi). The median time to progression after brachytherapy was
      11.6 months for patients with malignant meningioma and 10.4 months for the
      combined group. There was a trend toward longer disease-free survival time in
      patients after gross total resection versus subtotal resection and in patients
      with tumors located at the convexity and parasagittally versus at the cranial
      base. These differences did not reach statistical significance. The median
      overall survival after diagnosis was 9.4 years for patients with atypical
      meningioma, 6.6 years for those with malignant meningioma, and 8.0 years for all
      patients combined. Survival from the time of resection and implantation of (125)I
      was 1.6 years for patients with atypical meningioma, 2.4 years for patients with
      malignant meningioma, and 2.4 years for the combined group. Thirty-three percent
      of patients had complications requiring surgical intervention. Radiation necrosis
      occurred in 27% of patients; 13% underwent surgery for radiation necrosis. In
      addition, 27% had a wound breakdown and required surgical intervention.
      CONCLUSION: The options for patients with recurrent atypical or malignant
      meningiomas are limited. Our results suggest that for tumors not suitable for
      radiosurgery, resection followed by permanent brachytherapy should be considered
      as a potential salvage treatment. However, this approach results in a relatively
      high complication rate in these heavily treated patients and requires meticulous
      surgical technique and medical therapies to assist with wound healing after
      surgery.

PMID- 14683542
TI  - Connective tissue disorders with spontaneous spinal cerebrospinal fluid leaks and
      intracranial hypotension: a prospective study.
AB  - OBJECTIVE: Intracranial hypotension attributable to a spontaneous spinal
      cerebrospinal fluid (CSF) leak is an increasingly recognized cause of postural
      headaches. The cause of these leaks is poorly understood, but it is likely
      multifactorial and may involve a primary connective tissue disorder. We undertook
      a study to estimate the contribution of systemic connective tissue disorders to
      the development of spontaneous spinal CSF leaks. METHODS: We examined a group of
      18 consecutive patients with spontaneous spinal CSF leaks for features of a
      connective tissue disorder. RESULTS: The mean age of the 15 female patients and 3
      male patients was 38 years (range, 22-55 yr). Seven patients (38%) demonstrated
      stigmata of a systemic connective tissue disorder, and three distinct types of
      disorders could be identified, as follows. 1) The association of spontaneous
      spinal CSF leaks and minor skeletal features of Marfan syndrome was noted for
      three patients. 2) Ehlers-Danlos syndrome Type II was noted for two patients. 3)
      Joint hypermobility associated with marked attenuation of the dorsal muscular
      fascia, precluding proper wound closure, was noted for two patients. In addition,
      isolated small-joint hypermobility was observed for five patients (28%). Slit
      lamp ocular examinations, echocardiographic evaluations, histopathological
      examinations of skin biopsy specimens, and renal scanning did not reveal any
      other features of a systemic connective tissue disorder. CONCLUSION: Findings
      suggesting connective tissue disorders are common among patients with spontaneous
      spinal CSF leaks, and manifestations may be subtle. A variety of disorders can be
      identified, probably reflecting genetic heterogeneity. Problems with wound
      healing may occur as a result of the systemic nature of the underlying connective
      tissue disorder.

PMID- 14683543
TI  - Pilocytic and pilomyxoid hypothalamic/chiasmatic astrocytomas.
AB  - OBJECTIVE: Pilocytic astrocytoma (PA) is a common type of pediatric brain tumor
      that can arise within the hypothalamic/chiasmatic region and typically has an
      excellent outcome. We identified a group of tumors, previously classified as PAs,
      with unique histological features and aggressive behavior. This article describes
      the clinicopathological features of these unusual neoplasms, which are currently
      known as pilomyxoid astrocytomas (PMAs), to better differentiate them from
      typical PAs. METHODS: Medical information and surgical specimens were obtained
      for 42 PA cases and 21 PMA cases. Patient demographic features, treatment
      modalities, progression-free survival (PFS) times, overall survival (OS) times,
      and outcomes were compared between the groups with nonparametric tests. RESULTS:
      The PMA group included 12 male and 9 female patients. The PA group included 27
      male and 15 female patients. The mean ages at diagnosis for the PMA and PA groups
      were 18 months (range, 2-84 mo) and 58 months (range, 4-189 mo), respectively (P
      < 0.01). The mean PFS times for the PMA and PA groups were 26 and 147 months,
      respectively (P < 0.001). The mean OS times for the PMA and PA groups were 63 and
      213 months, respectively (P < 0.001). Sixteen patients with PMAs (76%)
      experienced local recurrence, and three of those patients demonstrated evidence
      of cerebrospinal fluid dissemination. Twenty-one patients with PAs (50%)
      experienced local recurrence, none with evidence of cerebrospinal fluid
      dissemination. Within the follow-up period, seven patients with PMAs (33%) and
      seven patients with PAs (17%) died as a result of their disease. In an age
      matched set, the mean PFS times for the PMA and PA groups were 25 and 163 months,
      respectively (P < 0.01), and the mean OS times for the PMA and PA groups were 60
      and 233 months, respectively (P < 0.001). CONCLUSION: Hypothalamic/chiasmatic
      PMAs occurred in a significantly younger population and were associated with
      substantially shorter PFS and OS times than were typical PAs. Increased
      recognition of these lesions could affect the prognosis and treatment of
      pediatric astrocytomas.

PMID- 14683544
TI  - Concussion in professional football: epidemiological features of game injuries
      and review of the literature--part 3.
AB  - OBJECTIVE: A 6-year study was performed to determine the circumstances, causes,
      and outcomes of concussions in the National Football League. METHODS: Between
      1996 and 2001, the epidemiological features of concussions were recorded by
      National Football League teams with a standardized reporting form. Symptoms were
      reported and grouped as general symptoms, cranial nerve symptoms, memory or
      cognitive problems, somatic complaints, and loss of consciousness. The medical
      actions taken were recorded. In total, 787 game-related cases were reported, with
      information on the players involved, type of helmet impact, symptoms, medical
      actions, and days lost. Concussion risks were calculated according to player game
      positions. RESULTS: There were 0.41 concussions per National Football League
      game. The relative risk was highest for quarterbacks (1.62 concussions/100 game
      positions), followed by wide receivers (1.23 concussions/100 game-positions),
      tight ends (0.94 concussion/100 game-positions), and defensive secondaries (0.93
      concussion/100 game-positions). The majority of concussions (67.7%) involved
      impact by another player's helmet. The remainder involved impact by other body
      regions of the striking player (20.9%) or ground contact (11.4%). The three most
      common symptoms of mild traumatic brain injury were headaches (55.0%), dizziness
      (41.8%), and blurred vision (16.3%). The most common signs noted in physical
      examinations were problems with immediate recall (25.5%), retrograde amnesia
      (18.0%), and information-processing problems (17.5%). In 58 of the reported cases
      (9.3%), the players lost consciousness; 19 players (2.4%) were hospitalized. A
      total of 92% of concussed players returned to practice in less than 7 days, but
      that value decreased to 69% with unconsciousness. CONCLUSION: The professional
      football players most vulnerable to concussions are quarterbacks, wide receivers,
      and defensive secondaries. Concussions involved 2.74 symptoms/injury, and players
      were generally removed from the game. More than one-half of the players returned
      to play within 1 day, and symptoms resolved in a short time in the vast majority
      of cases.

PMID- 14683545
TI  - Brainstem auditory evoked potential monitoring during microvascular decompression
      for hemifacial spasm: intraoperative brainstem auditory evoked potential changes
      and warning values to prevent hearing loss--prospective study in a consecutive
      series of 84 patients.
AB  - OBJECTIVE: The nerve function of Cranial Nerve VIII is at risk during
      microvascular decompression for hemifacial spasm. Intraoperative monitoring of
      brainstem auditory evoked potentials (BAEPs) can be a useful tool to decrease the
      danger of hearing loss. The aim of this study was 1) to assess the side effects
      of surgery on hearing and describe the main intraoperative BAEP changes observed
      in the authors' series, and 2) to define warning values beyond which the
      probability of hearing impairment rises significantly. These values were
      calculated by correlating the (possible) postoperative hearing disturbances
      evaluated in terms of pure tone average with intraoperative BAEP changes
      (especially delay in Wave V latency). METHODS: This series included 84
      consecutive patients affected with hemifacial spasm who underwent microvascular
      decompression during which BAEPs were monitored. During surgery, Wave I, I to V
      interpeak interval, latency, and amplitude of Wave V were recorded and measured.
      Auditory function was studied before and after surgery and expressed as a pure
      tone average in all patients. Then, correlations were made between hearing
      impairment after surgery and intraoperative BAEP changes in an attempt to define
      warning values. RESULTS: Seventy-four patients (88%) had no hearing loss after
      surgery (Group 1). Eight patients (9.5%) had hearing impairment with a decrease
      in pure tone average of more than 20 dB (Group 2). Two patients (2.3%)
      experienced a definitive and complete hearing loss on the side operated on (Group
      3). Among intraoperative BAEP changes, latency of Peak V was the most frequently
      observed and the most significant phenomenon, especially during cerebellar
      retraction and the decompression step of the microvascular decompression
      procedure. In the group of patients without hearing loss (Group 1), the mean
      delay in latency of Peak V was 0.61 millisecond (standard deviation, +/-0.36 ms);
      in the group with hearing decrease (Group 2), the mean delay was 1.05
      milliseconds (standard deviation, +/-0.64 ms); and in the group with deafness
      (Group 3), Wave V was abolished. CONCLUSION: From a practical standpoint, three
      warning values, based on delay in latency of Peak V, were established for use
      during surgery: an initial one at 0.4 millisecond ("watching" signal) at the
      safety limit; a second one at 0.6 millisecond (risk "warning" signal), which is
      the mean value corresponding to the group of patients without postoperative
      hearing loss; and an ultimate one at 1 millisecond ("critical" warning), before
      irreversibility. These warnings should help the surgeon to avoid or correct
      maneuvers that are dangerous for hearing function, which is mandatory in
      functional surgery.

PMID- 14683546
TI  - Minimally invasive surgical treatment of lumbar synovial cysts.
AB  - OBJECTIVE: Synovial cysts are a rare cause of lumbar radiculopathy and back pain.
      Surgical treatment is directed at complete excision of the cyst. We used
      minimally invasive surgical techniques for a series of patients, to assess the
      effectiveness of this approach for resection of synovial cysts. METHODS:
      Seventeen patients (10 female and 7 male patients) with presumed synovial cysts,
      as indicated on magnetic resonance imaging scans, underwent surgical resection
      with the 18-mm METRx tubular retractor system (Medtronic Sofamor Danek, Memphis,
      TN). A unilateral approach was used, with either an operating microscope (13
      cases) or a magnifying endoscope (4 cases), depending on the preference of the
      surgeon. Outcomes were reported by using modified MacNab criteria. RESULTS: The
      average patient age was 64 years (range, 46-82 yr). The L4-L5 level was most
      commonly affected (82% of cases). Grade 1 spondylolisthesis at the level
      harboring the synovial cyst was observed for 47% of the patients; all cases of
      spondylolisthesis involved the L4-L5 level. The mean operative time was 97
      minutes, and the average blood loss was 35 ml. Excellent or good results were
      achieved for 94% of the patients. A dural tear that did not violate the arachnoid
      membrane occurred during surgery for one patient but did not require further
      treatment. CONCLUSION: Synovial cysts can be effectively treated with a tubular
      retractor system in conjunction with an endoscope or microscope. Use of the
      tubular retractor minimizes soft-tissue trauma, incision length, blood loss, and
      disruption of ligamentous and bony structures. This may be particularly
      significant when synovial cysts are associated with spondylolisthesis, minimizing
      the risk of progressive instability and the need for fusion.

PMID- 14683547
TI  - Intraoperative speech mapping in 17 bilingual patients undergoing resection of a
      mass lesion.
AB  - OBJECTIVE: Language mapping has been reported previously for bilingual patients
      undergoing cortical resection of an epileptic focus that may have developed early
      in life. In this setting, the cortical organization of language may have been
      affected by the effects of having a seizure focus established early in life.
      Adults presenting with a primary brain tumor offer a different opportunity to
      study bilingual cortical representation of language sites, because presumably the
      brain has been unaffected by epilepsy during the first decade of life or beyond.
      In this analysis, we present the results for 17 bilingual patients who underwent
      speech mapping as part of the surgical procedure to remove a mass lesion.
      METHODS: The localization of cortical sites essential for language was assessed
      in 17 patients undergoing resection of a mass lesion. Stimulation mapping was
      performed in each language by use of an object-naming task. A site thought to be
      essential for naming was any site, in either language, in which interruption of
      naming (anomia) occurred in at least two-thirds of the stimulations at that site.
      RESULTS: A site essential for naming was identified in the exposed cortex for 5
      of 17 patients, whereas no essential site was found for 12 patients, presumably
      because of a limited surgical exposure. For the patients in whom a site essential
      for naming was identified, two patients displayed anomia in both languages, two
      others had anomia in only one language, and one showed anomia in one language but
      only hesitation of naming in the other language. CONCLUSION: Although no site was
      identified in the majority of the patients, those individuals in whom a site was
      identified demonstrate that bilingual patients undergoing tumor resection should
      be mapped for all languages regardless of patient age before it is decided which
      cortical and subcortical areas are safe to remove.

PMID- 14683548
TI  - Open-door cervical expansile laminoplasty.
AB  - Cervical laminoplasty is becoming a popular technique for the treatment of
      cervical myelopathy that is the result of multilevel canal stenosis. Many
      variations in this technique, which was originally created in Japan, have been
      developed, all with the goal of increasing canal space and reconstructing the
      posterior bony arch. We describe our extensive experience with this procedure for
      the treatment of cervical spondylotic myelopathy.

PMID- 14683549
TI  - Endoscopic transoral-transclival approach to the brainstem and surrounding
      cisternal space: anatomic study.
AB  - OBJECTIVE: The purpose of this study was to review the endoscopic anatomic
      features of the anterior brainstem and surrounding cisternal spaces via a
      transoral-transclival approach. METHODS: Fifteen adult human cadaveric heads,
      obtained from 10 fresh cadavers and 5 formalin-fixed cadavers, were used to
      demonstrate both the feasibility of an endoscopic transoral-transclival
      intradural approach and its exposure potential. To analyze the exact extension of
      a safe entry zone through the clivus, 20 skull bases were used to obtain anatomic
      measurements. RESULTS: The transoral approach was performed without maxillotomy
      or mandibulotomy and with a clival opening of 20 by 15 mm. Such a limited clival
      and dural opening allowed the insertion of the endoscope and instruments, full
      visualization of the anterolateral brainstem and cisternal spaces around it, and
      reconstruction of all anatomic layers by means of a paraendoscopic technique.
      CONCLUSION: The endoscopic transoral-transclival approach enables full access to
      the anterolateral brainstem and to the cisternal space around it. The use of the
      endoscope has the potential to reduce the need for a wider cranial base opening
      and the danger of postoperative complications.

PMID- 14683550
TI  - Mechanisms of disease: the blood-brain barrier.
AB  - OBJECTIVE: The blood-brain barrier (BBB) is often perceived as a passive
      membrane. However, evidence has demonstrated that the BBB plays an active role in
      normal homeostasis and in certain disease processes. METHODS: Approximately 300
      peer-reviewed publications that discussed normal or abnormal BBB function were
      reviewed. RESULTS: The role of the BBB and how it contributes to disorders of the
      central nervous system vary, depending on the specific disease process.
      CONCLUSION: In health and disease and extending to old age, endothelial cells,
      neurons, and glia constitute a neurovascular unit that regulates the BBB.
      Advances toward penetrating the BBB must account for both normal and abnormal
      functions of the neurovascular unit.

PMID- 14683551
TI  - Head injury and pulmonary embolism: a retrospective report based on the
      Pennsylvania Trauma Outcomes study.
AB  - OBJECTIVE: We retrospectively examined the database of the Pennsylvania Trauma
      Systems Foundation to determine the risk of pulmonary embolism in adult patients
      sustaining isolated head trauma or multiple injuries, including head trauma, to
      answer two questions: What is the incidence of symptomatic pulmonary embolism
      during hospitalization in a trauma center in patients who have sustained a head
      injury? Are patients with head injuries more at risk for pulmonary embolism than
      trauma patients without head injuries? METHODS: We determined the total number of
      adult submissions per year to the Pennsylvania Trauma Outcomes Study from 1992 to
      1996. Age, sex, Glasgow Coma Scale score, Abbreviated Injury Score for head
      injury, Injury Severity Score, intensive care unit days, hospital days, and the
      presence or absence of head injury, spinal injury, pelvic fractures, and/or femur
      fractures were recorded. Statistical techniques to evaluate their correlation
      with the incidence of pulmonary embolism included chi(2) testing, linear
      regression analysis, Kendall analysis, and logistic regression analysis. RESULTS:
      The average incidence of symptomatic pulmonary embolism in head-injured patients
      occurring during their acute hospital stay was 0.38%. This rate was not
      significantly greater than the 0.27% incidence of pulmonary embolism in patients
      without head injury. Factors that significantly increased this incidence were age
      greater than 45 years, Injury Severity Score greater than 15, male sex, and the
      presence of pelvic or femur fractures or of spinal cord injury. CONCLUSION: We
      found no evidence that head injury is a significant independent risk factor for
      development of symptomatic pulmonary embolism during the acute hospitalization of
      the trauma patient.

PMID- 14683552
TI  - De novo neurogenesis and acute stroke: are exogenous stem cells really necessary?
AB  - Recent studies documenting the phenomenon of de novo neurogenesis within the
      adult brain have propelled this area of research to the forefront of neuroscience
      investigations and stroke pathogenesis and treatment. Traditional theories have
      suggested that the central nervous system is incapable of neural regeneration;
      hence the emergence of the field of stem cell biology as a discipline devoted to
      uncovering novel forms of neural repair. However, several recent experimental
      observations have shown that the adult brain is capable of ongoing neurogenesis
      in discrete regions of the uninjured brain and additional forms of endogenous
      neural regeneration in the presence of an inciting event (induction
      neurogenesis). Induction neurogenesis has the potential for providing new
      insights into the cause and treatment of acute stroke syndromes.

PMID- 14683553
TI  - Measurements of the relative output factors for CyberKnife collimators.
AB  - OBJECTIVE: To determine accurately the relative output factors, defined as the
      ratio of the nominal dose rate for a given collimator to that of the 60-mm
      collimator. This is particularly important for radiosurgical treatment of
      functional disorders, such as trigeminal neuralgia, in which a single large
      radiation dose is delivered to the target with a small collimator, such as the 5
      mm collimator for CyberKnife radiosurgery. Numerous studies on the output factors
      have been reported for the Leksell gamma knife unit but none for the CyberKnife
      system. METHODS: Measurements of the relative output factors for all 12
      collimators were performed by three different methods: silicon diode,
      radiographic film, and thermoluminescent dosimetry microcubes. The silicon diode
      is designed for measurements in small (1-50 MV) photon beams performed in water
      or air. Film and thermoluminescent dosimetry measurements were performed in a
      plastic phantom. RESULTS: The measured relative output factors for the three
      methods were very similar except for the three smallest collimators (5, 7.5, and
      10 mm). The measured difference between the above methods was approximately 2%.
      The mean value of the output factor for the 5-mm collimator was 0.686 +/- 0.024.
      The uncertainties of the output factors are expected to increase with the
      decrease of collimator diameter. They range from approximately 1 to 4% of the
      relative output factor. CONCLUSION: The relative output factor can be measured
      with an acceptable accuracy even for the smallest (5-mm) CyberKnife collimators.
      This requires the selection of appropriate dosimetric detectors and measuring
      procedures. The results obtained with the diode are considered more accurate than
      with the other two methods.

PMID- 14683554
TI  - Perinidal dilated capillary networks in cerebral arteriovenous malformations.
AB  - OBJECTIVE: The perinidal vascular structures of cerebral arteriovenous
      malformations were examined, to clarify their pathomorphological features.
      METHODS: Twenty-two resected specimens of human brain structures adjacent to the
      nidus were examined. The vessels surrounding the nidus were three-dimensionally
      reconstructed with a computer graphics system. RESULTS: In all cases, the
      analysis of serial sections revealed that perinidal dilated capillaries were
      located in brain tissue 1 to 7 mm from the nidal border. The vessels surrounding
      the nidus demonstrated markedly dilated capillary networks (perinidal dilated
      capillary network [PDCN]). The diameters of the vessels forming the PDCN were 10
      to 25 times those of normal capillaries. The PDCN connected not only to the
      nidus, feeding arteries, and draining veins, via arterioles and venules, but also
      to the normal capillary network, arterioles, and venules. CONCLUSION: Without
      exception, each nidus was accompanied by a PDCN, which connected not only to the
      nidus, feeding arteries, and draining veins, via arterioles and venules, but also
      to normal capillaries, arterioles, and venules. The PDCN should be considered in
      studies aimed at gaining an understanding of the mechanisms underlying the
      intraoperative and postoperative bleeding, growth, and recurrence of surgically
      treated cerebral arteriovenous malformations.

PMID- 14683556
TI  - Vaccine therapy for murine glioma using tumor cells genetically modified to
      express B7.1.
AB  - OBJECTIVE: In a syngeneic mouse brain tumor model, we tested the hypothesis that
      vaccination with tumor cells genetically modified to express B7.1 molecules
      induces tumor-specific T cells and immunological antitumor effects. METHODS:
      Malignant glioma cells (RSV-MG) derived from a C3H/He mouse induced by Schmidt
      Ruppin Rous sarcoma virus (RSV) were infected with an adenovirus encoding the
      B7.1 gene (AdB7). To investigate the effects of B7.1 expression on the
      tumorigenicity of RSV-MG cells, infected cells were implanted subcutaneously into
      C3H/He mice. The C3H/He mice were vaccinated with AdB7 transfectants injected
      subcutaneously and 2 weeks later were challenged intracerebrally with wild-type
      RSV-MG cells to determine whether or not the expression of B7.1 would enhance the
      immunogenicity of RSV-MG cells. RESULTS: Immunocytochemistry confirmed the
      expression of B7.1 and major histocompatibility complex Class I antigen on the
      infected cells. The growth of subcutaneous tumors was markedly retarded in the
      AdB7 group, whereas tumors had formed and progressively increased in size in the
      other control groups. In the vaccine experiments, the mice immunized with AdB7
      transfectants survived longer than did the mice of the other groups, and a
      significant difference in survival times was noted. Immunocytochemistry revealed
      that brain tumors in mice previously vaccinated with AdB7 infectants had been
      infiltrated by a larger number of CD3(+) lymphocytes and that these CD3(+)
      lymphocytes contained not only CD4(+) and CD8(+) T cells but also CD25(+)
      activated T cells. In addition, a cytotoxicity assay confirmed that vaccination
      with the AdB7 transfectants induced tumor-specific cytotoxicity. CONCLUSION:
      These results demonstrate the therapeutic potential of vaccination with tumor
      cells expressing B7.1 for the treatment of malignant glioma.

PMID- 14683555
TI  - Endoscopic instrumented posterolateral lumbar fusion with Healos and recombinant
      human growth/differentiation factor-5.
AB  - OBJECTIVE: The goal of this study was to use a minimally invasive endoscopic
      surgical technique in a sheep model to evaluate the efficacy of an osteoinductive
      growth factor, recombinant human growth/differentiation factor-5 (also designated
      MP52), and an osteoconductive matrix formulation (Healos; DePuy AcroMed, Inc.,
      Mountain View, CA) for inducing and facilitating bone formation. METHODS: Twelve
      mature sheep underwent bilateral posterolateral lumbar fusion and pedicle screw
      fixation via a posterior endoscopic approach. Each sheep received two different
      types of graft material, autogenous iliac crest bone, or a bone graft substitute
      (MP52 with Healos), inserted into the right and left sides of the spine in an
      alternating fashion. Groups of four sheep were killed at 2, 4, and 6 months
      postoperatively for manual, radiographic, and histological evaluation. RESULTS:
      No neurological impairments, infections, or other complications were observed.
      After 2 months, partial fusion on both sides was observed, but radiographic
      evaluation showed greater bone growth on the side that received the bone graft
      substitute. Solid posterolateral fusion was observed in both autograft and bone
      graft substitute sites at 4 and 6 months, and autograft and Healos MP52 fusion
      sites were essentially the same at histological examination. There was no
      abnormal overgrowth of new bone from either of these two materials. CONCLUSION:
      Endoscopic posterolateral lumbar arthrodesis and instrumentation is feasible,
      safe, and effective in a sheep model. Healos is a useful bonding agent that
      mimics natural bone in posterolateral intertransverse fusion sites. Combined with
      MP52, it produced fusion comparable to that of autogenous bone graft. Minimally
      invasive techniques and bone graft substitutes could eliminate morbidity and
      increase the likelihood of successful fusion.

PMID- 14683557
TI  - Bilateral anterior thalamic nucleus lesions and high-frequency stimulation are
      protective against pilocarpine-induced seizures and status epilepticus.
AB  - OBJECTIVE: The thalamus is thought to play an important role in secondary
      generalization of seizures. The aim of the present study was to investigate the
      influence of anterior thalamic nucleus lesions and high-frequency stimulation in
      the pilocarpine model of secondarily generalized seizures in rats. METHODS: Adult
      Wistar rats underwent unilateral (n = 7) or bilateral anterior nucleus
      thalamotomies (n = 10), or unilateral (n = 4) or bilateral (n = 9) anterior
      thalamic nucleus stimulation through implanted electrodes. Control animals (n =
      9) received bilateral implants but no stimulation. Seven days after these
      procedures, animals were provided pilocarpine (320 mg/kg intraperitoneally) to
      induce seizures and status epilepticus (SE). Electrographic recordings from
      hippocampal and cortical electrodes were evaluated, and ictal behavior was
      assessed. RESULTS: In the control group, 67% of the animals developed SE 15.3 +/-
      8.8 minutes after pilocarpine administration. Neither unilateral anterior nucleus
      lesions nor stimulation significantly reduced the propensity or latency for
      developing seizures and SE. Bilateral thalamic stimulation did not prevent SE
      (observed in 56% of the animals), but it significantly prolonged the latency to
      its development (48.4 +/- 17.7 min, P = 0.02). Strikingly, no animal with
      bilateral anterior nucleus thalamotomies developed seizures or SE with
      pilocarpine. CONCLUSION: Bilateral anterior thalamic nuclear complex stimulation
      and thalamotomies were protective against SE induced by pilocarpine.

PMID- 14683558
TI  - The birth of stereotactic surgery: a personal retrospective.
AB  - The field of human stereotactic surgery was born at Temple Medical School in
      Philadelphia in 1947, with Ernst A. Spiegel and Henry T. Wycis its parents. I had
      the great fortune of walking into Dr. Spiegel's laboratory as a freshman medical
      student looking for a summer research project in 1956, when the field was just
      emerging from its infancy, and worked with Spiegel and Wycis for most of the next
      13 years and Rolf Hassler the following year. The perspective of the early growth
      of the field of stereotactic surgery from this unique position and my wanderings
      through the field as it grew, contracted, and then blossomed are presented.

PMID- 14683559
TI  - Thymic carcinoma presenting as cranial metastasis with intradural and
      extracranial extension: case report.
AB  - OBJECTIVE AND IMPORTANCE: Thymic carcinoma is an uncommon malignant tumor that is
      different from thymoma. Cranial and brain metastases from this tumor are
      extremely rare. We report a thymic carcinoma with cranial metastasis and discuss
      the behavior of this tumor. CLINICAL PRESENTATION: A 50-year-old man presented
      with headache and a palpable scalp tumor. Computed tomographic scans and magnetic
      resonance images revealed an osteolytic tumor with intradural and extracranial
      extension in the right occipital bone. INTERVENTION: After gross total resection
      and histological diagnosis, further investigation revealed a primary thymic tumor
      in the anterior upper mediastinum and liver metastases. The patient received
      multiple-cycle chemotherapy (cisplatin and gemcitabine) for primary and
      metastatic lesions. CONCLUSION: Thymic carcinoma has a poor prognosis because of
      a high degree of malignancy, early metastasis, and delayed diagnosis. Thus,
      treatment of a patient with this tumor calls for prompt diagnosis, surgical
      treatment, and optimal adjuvant therapy.

PMID- 14683560
TI  - Intraventricular solitary fibrous tumor: an unusual tumor with radiological,
      ultrastructural, and immunohistochemical evaluation: case report.
AB  - OBJECTIVE AND IMPORTANCE: Intracranial solitary fibrous tumors have been
      described previously, but intraventricular solitary fibrous tumors are extremely
      rare. We present what is, to our knowledge, the first reported case of solitary
      fibrous tumor in the third ventricle. CLINICAL PRESENTATION: A 63-year-old man
      presented with weakness of his lower extremities and headaches. Computed
      tomography and magnetic resonance imaging of the brain revealed an enhancing mass
      in the posterior part of the third ventricle. INTERVENTION: The tumor originated
      from the wall of the left internal cerebral vein and extended to the posterior
      part of the third ventricle. Nearly total excision was performed via an
      infratentorial-supracerebellar approach. CONCLUSION: The differential diagnosis
      of intracranial solitary fibrous tumors includes fibroblastic meningioma,
      meningeal hemangiopericytoma, neurofibroma, and schwannoma. The differential
      diagnosis in the present case was greatly helped by the immunohistochemical and
      ultrastructural findings, along with a disease-free 3.5-year follow-up. These
      findings are presented with reference to previous reports.

PMID- 14683561
TI  - Bivalirudin for endovascular intervention in acute ischemic stroke: case report.
AB  - OBJECTIVE AND IMPORTANCE: Intra-arterial thrombolysis has been demonstrated to
      improve recanalization and outcomes among patients with acute ischemic stroke.
      However, thrombolytic agents have limited effectiveness and are associated with a
      significant risk of bleeding. Bivalirudin is a direct thrombin inhibitor that has
      been demonstrated in the cardiology literature to have a more favorable efficacy
      and bleeding profile than other antithrombotic medications. We report the use of
      bivalirudin during endovascular treatment of acute stroke, when hemorrhagic
      complications are not uncommon. CLINICAL PRESENTATION: A 71-year-old woman with
      atrial fibrillation presented with right hemiparesis and aphasia and was found to
      have a National Institutes of Health Stroke Scale score of 10. Computed
      tomographic scans revealed no evidence of intracranial hemorrhage, aneurysm, or
      ischemic stroke. Cerebral angiography revealed thromboembolic occlusion of the
      superior division of the left middle cerebral artery. INTERVENTION: For
      anticoagulation, a loading dose of bivalirudin was intravenously administered
      before the interventional procedure, followed by continuous infusion. Attempts to
      remove the clot with an endovascular snare failed to induce recanalization of the
      vessel. Bivalirudin was then administered intra-arterially. Immediate
      postprocedural angiography demonstrated restoration of flow in the left middle
      cerebral artery. Repeat computed tomographic scans demonstrated no intracranial
      hemorrhage. The patient's hemiparesis and aphasia were nearly resolved and her
      National Institutes of Health Stroke Scale score was 2 at the time of her
      discharge 5 days later. CONCLUSION: To our knowledge, this is the first report of
      the use of bivalirudin for treatment of acute ischemic stroke. Bivalirudin may be
      a useful agent for intravenous anticoagulation and intra-arterial thrombolysis in
      this setting.

PMID- 14683562
TI  - Hiccups attributable to syringobulbia and/or syringomyelia associated with a
      Chiari I malformation: case report.
AB  - OBJECTIVE AND IMPORTANCE: Approximately 20 to 50% of patients with syringomyelia
      associated with Chiari malformations exhibit cranial nerve or cerebellar
      symptoms. However, hiccups represent a rare clinical manifestation of this
      disorder. We report a case of intractable hiccups resulting from syringobulbia
      associated with a Chiari I malformation, which was successfully treated with
      foramen magnum decompression. CLINICAL PRESENTATION: We report the case of a
      patient who presented with syringomyelia and syringobulbia associated with a
      Chiari I malformation, manifested as intractable hiccups and neurological
      deficits. Magnetic resonance imaging scans demonstrated syringobulbia in the
      dorsal medullary region and a large cervical syrinx from C2 to C6-C7, associated
      with a Chiari I malformation. INTERVENTION: Foramen magnum decompression and a C1
      laminectomy were performed. One month later, the intractable hiccups disappeared
      and the neurological symptoms demonstrated improvement. CONCLUSION: Postoperative
      magnetic resonance imaging scans demonstrated enlargement of the subarachnoid
      space in the posterior fossa and disappearance of the syringobulbia. There has
      been no recurrence of intractable hiccups and syringobulbia in 6 months after
      surgery. Magnetic resonance imaging of the brainstem is an important diagnostic
      procedure for intractable hiccups, because syringobulbia associated with a Chiari
      malformation represents a surgically treatable disorder, although the incidence
      is low.

PMID- 14683563
TI  - Supernumerary phantom limbs associated with left hemispheric stroke: case report
      and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Supernumerary phantom limb (SPL) is extremely rare.
      Literature reports noted 17 cases that occurred after right cerebral hemispheric
      stroke and 2 cases that occurred after left cerebral hemispheric stroke, but
      without imaging diagnoses. CLINICAL PRESENTATION: A 45-year-old male patient
      complained of SPLs on the right side after recurrent left thalamic hemorrhage.
      Computed tomography and magnetic resonance imaging demonstrated the lesion
      causing the left hemispheric stroke. INTERVENTION: The patient was treated
      conservatively. Computed tomographic scans demonstrated that the lesion had
      disappeared by 15 days after admission. The sensation of SPLs disappeared after
      28 days. CONCLUSION: SPL may occur among patients with left hemispheric stroke,
      especially those with lesions in the thalamus, spastic paresis on the right side
      immediately after stroke, and psychiatric disorders such as alcohol and tobacco
      intoxication.

PMID- 14683564
TI  - Continuous laryngoscopic vocal cord monitoring for vascular malformation surgery
      in the medulla oblongata: technical note.
AB  - OBJECTIVE: Resection of lesions located in the medulla oblongata may result in
      significant morbidity. The most lethal complications are swallowing disturbances,
      which can lead to aspiration pneumonia. To prevent this problem, the lower
      cranial nerves can be mapped with recording needles placed in the posterior
      pharyngeal wall and the tongue. However, mapping alone is not sufficient to
      preserve the lower cranial nerves and swallowing functions. To overcome this
      problem, we attempted to devise a method to intraoperatively monitor vocal cord
      movements with a laryngoscope. We used this method, in addition to other types of
      brainstem mapping, in three cases. METHODS: Recording needles were inserted into
      the posterior pharyngeal wall and the tongue, to record the responses of Cranial
      Nerves IX and XII. A laryngoscope was inserted orally, for direct observation of
      vocal cord movements, and was maintained until the end of the operation. The
      floor of the fourth ventricle was stimulated with a monopolar stimulator.
      Somatosensory evoked potentials, auditory evoked potentials, and motor evoked
      potentials were simultaneously monitored. RESULTS: We were able to confirm
      synchronized vocal cord adduction with stimulation of the expected vagal trigonum
      location and to monitor rhythmic vocal cord movements during spontaneous
      respiration. In all three cases, we removed the lesions without postoperative
      complications. CONCLUSION: In addition to intraoperative vocal cord monitoring
      with a laryngoscope, we could safely determine the optimal location for the first
      incision in the floor of the fourth ventricle. Potentially lethal postoperative
      complications can be avoided with brainstem mapping and vocal cord monitoring.

PMID- 14683565
TI  - Editorial: Health psychology and public health--bridging the gap.

PMID- 14683566
TI  - Health psychology and public health: theoretical possibilities.
AB  - Public health has either implicitly or explicitly drawn upon a range of
      psychological theories. This paper identifies four areas where the application of
      such theory could be developed, health communication, environmental initiatives,
      the negotiation of behaviour and participation and empowerment. Recommendations
      are made regarding content, sources and recipient characteristics that can be
      used to develop targeted health communication campaigns. Psychology also has a
      role to play in informing structural approaches to prevention. To facilitate
      this, a framework which focuses on cues, reinforcer and barriers and an
      understanding of how behaviour is achieved through negotiation and interaction is
      outlined. Finally we highlight a role for psychology in approaches that focus on
      participation and empowerment in relation to health.

PMID- 14683567
TI  - Diagnostic and treatment decisions in US healthcare.
AB  - The practice of medicine links diagnosis to treatment. However, for many
      diagnosed conditions diagnosis and treatment may not affect health outcome.
      Examples include low-grade cancers that do not influence life expectancy or
      quality of life. Further, there is considerable uncertainty about the point along
      a biologic continuum where treatment should begin. Changes in diagnostic
      thresholds often increase healthcare costs even though the benefit of the
      treatment is uncertain. Although this uncertainty is understood by the healthcare
      providers, it often is not shared with patients. We advocate a new paradigm
      called shared medical decision making that makes uncertainty about diagnosis and
      treatment transparent to patients and engages them in the treatment decision
      process.

PMID- 14683568
TI  - Public health psychology: a conceptual and practical framework.
AB  - Increasingly, the development of public health infrastructures requires
      psychology to reevaluate its contribution to public health at local, national and
      global levels. Already familiar to some psychologists, particularly those in
      community psychology and health promotion, the expansion of public health has
      implications for psychology in terms of knowledge/practice and working
      differently in multidisciplinary settings. In this article, I provide a critical
      overview of the implications of the historical and international development of
      health psychology and the changing nature of public health to strengthen the
      establishment of public health psychology. A conceptual and practical framework
      is proposed in which public health psychology theory, methods and practice are
      considered as well as its relevance to the health social sciences more generally.

PMID- 14683569
TI  - Discursive practices and democratic participation: negotiating language use in
      mental health services.
AB  - Collective health refers to a field of knowledge that was developed in Latin
      America in the 1970s. In Brazil, it has been intrinsically related to the
      creation of the Unified Health System. One of the key notions in this new health
      system is integrality of care: the development of responses that are sensitive to
      the health needs of the population. This study takes integrality as its context
      and explores the meaning of mental suffering for users of mental health services.
      Three aspects are discussed: the population's lack of knowledge about what is
      offered; the difficulty in translating 'mental suffering' into a language
      understood by health care professionals; and the tendency to deny this suffering
      because of the fear of stigmatization.

PMID- 14683570
TI  - Health psychological theory in promoting population health in Paijat-Hame,
      Finland: first steps toward a type 2 diabetes prevention study.
AB  - In public health promotion, behavioural science theories and theory-based methods
      should be translated into practical strategies that fit environmental conditions
      and are feasible for implementation. In this article, an effort to meet this
      challenge is presented. As a starting point we describe the conditions for
      development and success of the previous generation of public health promotion
      programmes in Finland. However, changes both in the population structure and in
      the population health bring new demands for programme development. We consider
      possibilities offered by health psychology and give a practical example of how
      theories and theory-based methods are applied in a community programme for type 2
      diabetes prevention implemented in the Finnish primary health care.

PMID- 14683571
TI  - Intervention mapping: protocol for applying health psychology theory to
      prevention programmes.
AB  - Evidence-based health promotion programmes are based on empirical data and
      theory. While a broad range of social and behavioural science theories are
      available, the actual application of these theories in programme design remains a
      real challenge for health promotion planners. Intervention Mapping describes a
      protocol for the development of theory- and evidence-based health promotion
      programmes. It provides guidelines and tools for the selection of theoretical
      foundations and underpinnings of health promotion programmes, for the application
      of theory, and for the translation of theory in actual programme materials and
      activities. This article presents the protocol and elaborates on the application
      of theory, using examples from successful intervention programmes.

PMID- 14683572
TI  - Psychosocial determinants of premature health deterioration in a changing
      society: the case of Hungary.
AB  - The drastic increase of morbidity and mortality rates in the transforming Central
      Eastern European countries, characterizing the last decades, offers a unique
      opportunity to analyse the relationship of those social, psychological and
      biological processes that contribute to rapid health modifications. In 1988 and
      1995, two national representative surveys of the Hungarian population aged 16 or
      older (N = 20,902 and 12,640 respectively) were conducted. The results show that
      depressive symptom severity mediates between relative socio-economic deprivation
      and higher self-rated morbidity rates. The worsening of traditional risk factors
      such as alcohol consumption and smoking, are also the consequences of social and
      psychological problems. A vicious circle might be hypothesized between social
      deprivation and depressive symptomatology, which substantially contributes to
      higher morbidity and mortality rates.

PMID- 14683573
TI  - Interplay between self and community: a role for health psychology in Eastern
      Europe's public health.
AB  - It is a well-known phenomenon that since the 1970s, there has been a growing
      difference in health status between populations in Eastern Europe and those in
      western countries. This phenomenon has been found to relate to unhealthy
      lifestyles. Individuals' health behavior, as a part of their lifestyle, stems
      from an interplay between self and community; between individual traits and
      states, and community orientations. Theories of health psychology should play an
      important role in Eastern Europe's public health. One of the biggest challenges
      in this process is the lack of people's motivation rooted in the harmful
      psychological effects of the past socialist dictatorship in this region. There is
      a need for converting learned helplessness, often found in people because of the
      nature and collapse of the old regime, into learned optimism.

PMID- 14683574
TI  - Psychology and the workers' health movement in the state of Sao Paulo (Brazil).
AB  - This article discusses the ways in which psychology has contributed to a new
      range of public health services concerned with the health of working people in
      the State of Sao Paulo, Brazil. It begins by discussing the political,
      institutional and theoretical bases from which the Workers' Health Movement
      emerged in the early 1980s as a replacement for previous approaches to
      occupational health. It provides examples of some of the different actions and
      practices that were developed and which had a key role in the battle for better
      working conditions and for an enhanced role for workpeople in organizational
      change. Finally it shows how the dialogue between the field of Workers' Health
      and psychology was crucial for the construction of psychology's social agenda.

PMID- 14683575
TI  - Discourses in the European Commission's 1996-2000 Health Promotion Programme.
AB  - This article is a discourse analysis of 'The Community Action Programme on Health
      Promotion, Information, Education and Training 1996-2000'. The analysis uses six
      stages to discourse analysis. A religious discourse is used to construct the
      Programme and a military discourse is used to construct its implementation. These
      discourses are embedded in a scientific discourse. This analysis reveals that
      despite rhetorical endorsement of the concept of empowerment in health promotion,
      this Programme disempowers through vagueness, clear hierarchies of power and an
      emphasis on scientific methods of evaluation. The analysis also reveals that
      there has been a shift in blame in recent health promotion policy, the reflection
      is now on the collective as opposed to individual behaviour.

PMID- 14683576
TI  - Meat consumption and commitments on meat policy: combining individual and public
      health.
AB  - Although meat consumption plays a significant role for individual and public
      health, there is only little empirical research on the motives of meat
      consumption informed by health psychology and hardly any on socio-political
      commitments concerning general meat production taking on a public health
      perspective. To fill this gap, a questionnaire study was conducted to examine the
      links between both disciplines. Correlational and multiple regression analyses
      reveal that individual meat consumption is primarily based on self-centred
      judgments of control beliefs protecting ones health and of taste, whereas socio
      political commitments are based on a mixture of self-centred judgments and animal
      ethics. Based on these results, it is concluded, that models on health behaviour
      should integrate the social perspective, and that in intervention programs issues
      of individual as well as public health should be given equal importance.

PMID- 14683577
TI  - Health policy perception and health behaviours: a multilevel analysis and
      implications for public health psychology.
AB  - Associations of health policy perception with health behaviours are analysed.
      Policy perception is differentiated in information about programmes and appraisal
      of health policy's contribution to policy goals, and conceptualized on the level
      of: (1) individuals; and (2) populations (as a social climate indicator). Survey
      data from the Biomed2-Project MAREPS gathered in Belgium, Finland, Germany, The
      Netherlands, Spain and Switzerland (N= 3343) show that at the individual level,
      only policy information is associated with utilizing mammography, quitting
      smoking, physical activity and political participation in creating healthy
      environments. In contrast, multilevel regression analyses show that policy
      appraisal is related to physical activity and political participation as a social
      climate factor. Implications for integrating health psychology and public health
      within public health psychology are discussed.

PMID- 14683585
TI  - Electroporation as a method for the efficient in vivo delivery of therapeutic
      genes.

PMID- 14683586
TI  - IL-12 gene therapy using an electrically mediated nonviral approach reduces
      metastatic growth of melanoma.
AB  - Interleukin-12 (IL-12) has been evaluated in both preclinical and clinical
      immunotherapy protocols as a potential therapy for melanoma. However, delivery of
      IL-12 in the form of recombinant protein can result in severe toxicity, and gene
      therapy has had limited success against B16.F10 murine melanoma. This study
      investigated the therapeutic effect of delivering a plasmid encoding IL-12
      followed by electroporation on primary and secondary tumors. Three treatments of
      intratumoral (i.t.) plasmid injection and electroporation resulted in 80% of mice
      with B16.F10 melanoma tumors being tumor free for >100 days (cure). The "cured
      animals" were resistant to challenge with B16 cells. In a separate experiment,
      B16 cells were injected on the opposite flank of the treated tumor on the day of
      treatment. Eighty-seven percent of control mice developed a distant tumor while
      only 43.8% of mice receiving two or three i.t. electroporation treatments
      developed a distant tumor. For examination of tumor development in the lungs,
      mice were injected intravenously with B16.F10 cells then treated with i.m.
      injections of plasmid with or without electroporation. Only 37.5% of mice
      receiving i.m. injections and electroporation developed nodules in the lungs
      compared to 87.5% of mice in the no-treatment group. The results show that
      administration of a plasmid encoding IL-12 with electroporation has a therapeutic
      effect on primary tumors as well as distant tumors and metastases.

PMID- 14683587
TI  - Effects of electrogenetherapy with p53wt combined with cisplatin on curvival of
      human tumor cell lines with different p53 status.
AB  - The aim of our study was to evaluate electrogenetherapy with p53wt alone or
      combined with cisplatin on two colorectal (HT-29 and LoVo) and two prostatic (PC
      3 and Du145) carcinoma cell lines with different p53 status. In addition, the
      feasibility of electrogenetherapy with p53wt was tested also in vivo on PC-3
      prostatic cancer xenografts. Electrogenetherapy with p53wt was dependent on the
      p53 status of the cell lines used. Electrogenetherapy was the most effective on
      the PC-3 (p53 null) and Du145 (p53mt) cells, and to the much lesser extent in
      LoVo cells (p53wt). The exception was the HT-29 cell line with overexpressed
      mutated p53, where electrogenetherapy with p53wt was the least effective.
      Sensitivity of the cell lines to cisplatin was independent of the p53 status.
      Furthermore, the presence of exogenous p53 due to electrogenetherapy did not
      enhance cisplatin cytotoxicity, since the combination of these therapies resulted
      in additive cytotoxic effect. The effectiveness of electrogenetherapy with p53wt
      was also demonstrated in vivo by successful treatment of subcutaneous PC-3 tumors
      in mice. In conclusion, our study shows that electrogenetherapy with p53wt is
      feasible, and resulted in comparable cytotoxic and antitumor effectiveness to
      viral-mediated p53wt gene therapy. This therapy was effective and dependent on
      the p53 status of the tumor cell lines. Combination of electrogenetherapy and
      cisplatin resulted in additional cell kill by cisplatin, and was not dependent on
      the p53 status.

PMID- 14683588
TI  - Cell and animal imaging of electrically mediated gene transfer.
AB  - Electropermeabilization is a nonviral method successfully used to transfer genes
      into cells in vitro as in vivo. Although it shows promise in field of gene
      therapy, very little is known on the basic processes supporting the DNA transfer.
      The aim of the present investigation is to visualize gene electrotransfer and
      expression both in vitro and in vivo. In vitro studies have been performed by
      using digitized fluorescence microscopy. Membrane permeabilization occurs at the
      sides of the cell membrane facing the two electrodes. A free diffusion of
      propidium iodide across the membrane to the cytoplasm is observed in the seconds
      following electric pulses. Fluorescently labeled plasmids only interact with the
      electropermeabilized side of the cell facing the cathode. The plasmid interaction
      with the electropermeabilized cell surface is stable over a few minutes. Changing
      the polarity and the orientation of the pulses lead to an increase in gene
      expression. In vivo experiments have been performed in Tibialis Cranialis mice
      muscle. Electric field application lead to the in vivo expression of plasmid DNA.
      We directly visualize gene expression of the Green Fluorescent Protein (GFP) on
      live animals. GFP expression is shown to be increased by applying electric field
      pulses with different polarities and orientations.

PMID- 14683589
TI  - Diverse effects of nanosecond pulsed electric fields on cells and tissues.
AB  - The application of pulsed electric fields to cells is extended to include
      nonthermal pulses with shorter durations (10-300 ns), higher electric fields (<
      or =350 kV/cm), higher power (gigawatts), and distinct effects (nsPEF) compared
      to classical electroporation. Here we define effects and explore potential
      application for nsPEF in biology and medicine. As the pulse duration is decreased
      below the plasma membrane charging time constant, plasma membrane effects
      decrease and intracellular effects predominate. NsPEFs induced apoptosis and
      caspase activation that was calcium-dependent (Jurkat cells) and calcium
      independent (HL-60 and Jurkat cells). In mouse B10-2 fibrosarcoma tumors, nsPEFs
      induced caspase activation and DNA fragmentation ex vivo, and reduced tumor size
      in vivo. With conditions below thresholds for classical electroporation and
      apoptosis, nsPEF induced calcium release from intracellular stores and subsequent
      calcium influx through store-operated channels in the plasma membrane that
      mimicked purinergic receptor-mediated calcium mobilization. When nsPEF were
      applied after classical electroporation pulses, GFP reporter gene expression was
      enhanced above that observed for classical electroporation. These findings
      indicate that nsPEF extend classical electroporation to include events that
      primarily affect intracellular structures and functions. Potential applications
      for nsPEF include inducing apoptosis in cells and tumors, probing signal
      transduction mechanisms that determine cell fate, and enhancing gene expression.

PMID- 14683591
TI  - Optimization of electroporation parameters for the intramuscular delivery of
      plasmids in pigs.
AB  - Increased transgene expression after plasmid transfer to the skeletal muscle is
      obtained with electroporation in many species, but optimum conditions are not
      well defined. Using a plasmid with a muscle-specific secreted embryonic alkaline
      phosphatase (SEAP) gene, we have optimized the electroporation conditions in a
      large mammal (pig). Parameters tested included electric field intensity, number
      of pulses, lag time between plasmid injection and electroporation, and plasmid
      delivery volume. Electric pulses, between 0.4 and 0.6 Amp constant current,
      applied 80 sec after the injection of 0.5 mg SEAP-expressing plasmid in a total
      volume of 2 mL produced the highest levels of expression. Further testing
      demonstrated that electroporation of a nondelineated injection site reduces the
      levels of SEAP expression. These results demonstrate that electroporation
      parameters such as amperage, lag time, and the number of pulses are able to
      regulate the levels of reporter gene expression in pigs.

PMID- 14683592
TI  - Accelerated immune response to DNA vaccines.
AB  - DNA vaccines offer considerable promise for improvement over conventional
      vaccines. For the crucial step of delivering DNA vaccines intracellularly,
      electroporation (EP) has proven to be highly effective. This method has yielded
      powerful humoral and cellular responses in various species, including nonhuman
      primates. In an attempt to further improve DNA vaccination we used micron-size
      gold particles (which do not bind or adsorb DNA) as a particulate adjuvant which
      was coinjected with DNA intramuscularly into mice, followed by EP of the target
      site. The presence of gold particles accelerated the antibody response
      significantly. Maximum titers against hepatitis B surface antigen (HBsAg) were
      reached after one boost in 6 weeks, whereas 8 weeks were required without
      particles. These immunizations were effective in protecting mice against tumor
      challenge with cancer cells expressing HBsAg as a surrogate cancer antigen.
      Computer modeling of electric fields and gene expression studies indicate that
      gold particles do not stimulate EP and subsequent antigen expression. The
      particles may act as an attractant for immune cells, especially antigen
      presenting cells. We conclude that particulate adjuvants combined with DNA
      vaccine delivery by EP reduces the immune response time and may increase vaccine
      efficacy. This method may become valuable for developing prophylactic as well as
      therapeutic vaccines. The rapid response may be of particular interest in
      countering bio-terrorism.

PMID- 14683590
TI  - Electroporation of the vasculature and the lung.
AB  - Electroporation has proven to be a highly effective technique for the in vivo
      delivery of genes to a number of solid tissues. In most of the reported methods,
      DNA is injected into the target tissue and electrodes are placed directly on or
      in the tissue for application of the electric field. While this works well for
      solid tissues, there are many tissues and organs that are not amenable to such an
      approach. In this review I will focus on the development of electroporation
      protocols for two such tissues: the vasculature and the lung. Several methods for
      in vivo electroporation of the vasculature have been developed in recent years
      that deliver DNA to vessel segments from either the inside or outside of the
      vessel. The advantages and disadvantages of each are discussed, as are the
      applications for which they have been used. In more recent work, our laboratory
      has developed a novel method to deliver genes to the rodent lung that results in
      high level, uniform, gene expression throughout all cell types of the lung. Most
      importantly, this technique is safe, and causes no inflammatory response or
      alterations in normal physiology of the organs. Taken together, these studies
      demonstrate the utility of electroporation for gene transfer to non injectible
      tissues.

PMID- 14683593
TI  - Modeling the electromobility of ions in a target tissue.
AB  - Electroporation is a clinical and laboratory technique for the delivery of
      molecules to cells. This method imposes electric fields onto cells or tissues
      through the use of electrodes and a set of electrical parameters to ultimately
      incorporate molecules into the cells. Clinical applications may include using
      directional fields to bring therapeutics to the target tissues before triggering
      an electroporation event. The choice of applicator may also have a significant
      influence on this molecular flow. Modeling ionic flow in tissues will yield
      insight into selecting the appropriate parameters or electroporation signature
      for a desired target application. In this paper, the motion of tissue injected
      ions was modeled for two common electroporation applicator configurations-the
      parallel plate, and the four needle electrodes. This electric field induced fluid
      flow model predicts that the parallel plate applicator ultimately directs the
      movement of an ionic therapeutic in a forward manner with side motion due only to
      obstruction, while the four-needle applicator directs anisotropic flow within the
      field ultimately forcing the therapeutic into a mound at the fringes of the
      induced electric field.

PMID- 14683594
TI  - Effect of imidazole on the solubility of a his-tagged antibody fragment.
AB  - A number of studies have demonstrated the limited solubility of single-chain Fv
      antibody fragments and its improvement by genetic engineering. This limits the
      stability of recombinant protein upon storage and the efficiency of chemical
      modification. The RAFT3 scFv used in the present work is specific for melanoma
      associated proteoglycan and an attractive candidate for clinical radioimaging
      studies because of its unusual radiolabelling properties. However, when expressed
      with a c-terminal his(6) IMAC purification tag, the recombinant protein starts to
      precipitate after column elution and dialysis against PBS and reaches a
      concentration of soluble protein of approximately 150 microg/mL within a few days
      upon storage at 4 degrees C. We tested several commonly used buffer modifications
      (addition of detergents, high salt, amino acids) to improve the solubility and
      stability of the protein but without any major improvement. However, we found
      that, when the final dialysis step was omitted and the protein left in IMAC
      column elution buffer (PBS containing imidazole), it remained soluble.
      Furthermore, several months old and precipitated protein could be redissolved in
      this buffer without loss of antigen binding. This observation and the largely pH
      independent nature of protein solubility suggest that neither salt bridges formed
      by the his(6) tail nor cross-linking of his(6) tails mediated by metal ions
      leached from the column during elution are responsible for the limited solubility
      of the protein in the absence of imidazole. The presence of imidazole did not
      interfere with radiolabelling and in vivo tumor targeting in a mouse model. The
      solubilizing and stabilizing effect of imidazole could be of use for his(6)
      tagged and poorly soluble recombinant proteins other than scFvs.

PMID- 14683595
TI  - Characterization of monoclonal antibody HTA125 with specificity for human TLR4.
AB  - Binding of monoclonal antibody HTA125 to human toll-like receptor 4 (TLR4) was
      characterized by flow cytometry using MonoMac6 human monocytic cells. Data were
      obtained using direct binding to cell surface TLR4 by labeled HTA125, as well as
      inhibition of direct binding using purified reagents, and by two-step binding.
      HTA125 bound weakly to human TLR4, and could be inhibited by mouse Ig, mouse IgG
      Fc, and mouse IgG2a. In addition, purified human IgG Fc and purified human
      immunoglobulin of isotypes IgG1 and IgG4 could block binding of HTA125 to
      MonoMac6 cells. Furthermore, a mouse IgG1 monoclonal antibody possessing
      specificity for human CD64, which is a high affinity IgG Fc receptor, partially
      inhibited binding of HTA125 to MonoMac6 cells. Finally, co-stimulation via TLR4
      and Fc receptor, resulted in cytokine production by MonoMac6 cells different than
      that induced via TLR4 alone. Therefore, the utility of HTA125 remains as a weak
      detector of human TLR4, and as an agent to block TLR4 ligands with an
      understanding that Fc receptor may be engaged also.

PMID- 14683596
TI  - A monoclonal antibody to a carbohydrate epitope expressed on glycolipid and on
      alpha3beta1 integrin on human esophageal carcinoma.
AB  - A mouse monoclonal antibody (MAb-9) produced by immunization with a human
      esophageal carcinoma cell line, TE-2 (derived from undifferentiated squamous cell
      carcinoma) reacted specifically with about 30% of esophageal carcinoma cell lines
      and tissue sections from clinical samples. MAb-9 showed minimal reactivity with
      normal esophageal tissue. (125)I, fluorescent or gold particle labeled MAb-9
      bound to TE-2 cell surfaces. (125)I-radiolabeled MAb-9 was used to detect
      reactive material from cell extracts in Western blot. Treatment of TE-2 membrane
      proteins with neuraminidase, N-glycanase or O-glycanase reduced antigen
      detection. Treatment of cells with periodic acid destroyed antibody binding in
      ELISA. Lipid extracts from cell membranes, containing glycolipids, also reacted
      with MAb-9. MAb-9 was used to purify target antigen from detergent solubilized
      membrane proteins and the prominent bands from subsequent gel electrophoresis
      were trypsin digested and analyzed by mass spectrometry. Peptides from alpha(3)
      and beta(1) integrin chains were identified. These data indicate that
      alpha3beta1integrin is prominently expressed on certain esophageal carcinomas and
      that a specific carbohydrate unit is selectively displayed on the alpha(3)
      integrin subunit as well as on glycolipid on the cell surface. The alpha3beta1
      integrin expressed on A-431 carcinoma cells does not display this carbohydrate
      epitope and is not detected by MAb-9. Thus, expression of the carbohydrate
      epitope is the basis for the tumor selective reaction of MAb-9 with a subset of
      esophageal carcinomas.

PMID- 14683597
TI  - Production and characterization of monoclonal antibodies against the
      vasoconstrictive peptide human urotensin-II.
AB  - We report the production and characterization of four monoclonal antibodies
      (MAbs) against human urotensin-II (hU-II). The antibodies were raised against
      human hU-II, which contains the C-terminus cyclic ring (CFWKYC) that is conserved
      across species. Multiple selection assays were applied to ensure antibody potency
      and reactivity against the ring structure. The MAbs reacted via ELISA with hU-II
      bound to plastic, immunoprecipitated [(125)I-Y(9)] hU-II, bound to biotinylated
      hU-II in BIAcore analysis and, by Western analysis, recognized the full-length
      human preprourotensin-II expressed in transfected HEK293 cells. All four MAbs
      cross-reacted with porcine A, porcine B, rat, mouse, and goby U-II in ELISA. By
      competitive RIA, hU-II(5-11) (identical to the C-terminus of goby U-II) reacted
      equivalently to hU-II and goby U-II. The IC(50)s were 0.8 nM for one MAb and 1.6
      nM for the others. All four MAbs reacted 15-fold less potently with hU-II(5-10)
      and 50-fold less potently with hU-II(5-10) amide. Thus, the ring structure and
      terminal Val/Ile comprise the binding site for this group of MAbs. This panel of
      antibodies could be useful tools to help delineate the biology and pharmacology
      of U-II. They may also be of diagnostic value in monitoring hU-II in body fluids.

PMID- 14683598
TI  - Development of a monoclonal antibody capable of detecting prolamine in wheat and
      oats.
AB  - A monoclonal antibody (MAb) capable of detecting the gliadin in wheat flour has
      been developed. By immunoblot, the monoclonal antibody recognized three bands in
      the membranes after electrophoresis in an SDS PAGE of the alcohol-soluble
      proteins of wheat, and only one band in the alcohol extract of the oat flour.
      ELISA technique can be applied using this monoclonal antibody in the detection of
      gliadin and avenin in samples from wheat or triticale. The characterization of
      the antibody shows that it is an IgM class. Sensitivity by ELISA to the gliadin
      was 80 ng/ml.

PMID- 14683599
TI  - Impact of the introduction of high-affinity specific monoclonal antibodies in the
      improvement of sensitivity and specificity parameters of UMELISA HBsAg PLUS and
      UMELISA TSH immunoenzymatic techniques.
AB  - Improvement in the sensitivity and specificity of UMELISA techniques as a result
      of the introduction of monoclonal antibodies superseding the use of polyclonal
      antibodies was studied. For this purpose, we performed a comparison of the
      results in the functioning of the screening programs before and after the
      introduction of monoclonal antibodies. We analyzed some parameters such as
      sensitivity, specificity and detection limit in the UMELISA HBsAg PLUS and
      UMELISA TSH techniques. The sensitivity and specificity parameters were evaluated
      by means of comparison with the commercial assays. The detection limit was
      calculated as the fluorescence of the calibrator 0 + 2 standard deviations. Since
      the introduction of MAb obtained for us an increase in the sensitivity,
      specificity, and positive predictive value was evidenced. On the other hand, the
      use of the MAb guarantees better stability in the diagnostic kit production
      process.

PMID- 14683600
TI  - Monoclonal antibodies to the recombinant protein TmpA of the Treponema pallidum.
AB  - Spleen cells from BALB/c mice immunized with recombinant TmpA were fused with
      mouse myeloma cells (P3/X63-Ag8), and five hybridomas secreting monoclonal
      antibodies were obtained. These hybridomas specifically recognize TmpA and do not
      cross-react with other molecules such as recombinant HBsAg of HBV and synthetic
      HCV core peptides. The monoclonal antibodies were IgG1 subclass and ascitic fluid
      from these hybridomas was purified by affinity chromatography on Protein A
      Sepharose CL-4B column to isolate the IgG1 active fraction. The affinity constant
      of these monoclonal antibodies ranged from 6.4 x 10(8) and 1.73 x 10(10) M(-1).

PMID- 14683601
TI  - Generation of a rat monoclonal antibody specific for importin alpha3/Qip1.
AB  - Importin alpha, which mediates the nuclear import of nuclear localization signal
      (NLS)-containing proteins, is a member of nuclear transport factors. Importin
      alpha binds directly NLS and functions as an adapter for accessing the importin
      beta-dependent import pathway. To date, several isoforms of importin alpha have
      been identified and classified into three subfamilies in higher eukaryotes. In
      this study, we report on the production of a rat monoclonal antibody (MAb)
      against importin alpha3/Qip1, a member of the importin alpha family, using a rat
      medial iliac lymph node method. The MAb 3D10 produced, reacted with both
      recombinant and endogenous importin alpha 3/Qip1. Immunoblotting analysis
      revealed that MAb 3D10 exclusively recognizes importin alpha3/Qip1 among members
      of the importin alpha family, in various mammalian cells.

PMID- 14683602
TI  - A novel competitive ELISA for both free and protein-bound nitrotyrosine.
AB  - 3-Nitro-L-tyrosine (nitrotyrosine) has recently been considered to be useful as a
      biomarker of endogenous production of several reactive nitrogen species including
      peroxynitrite. In the present study, nitrotyrosine was coupled to human serum
      albumin (HSA) using a two-step glutaraldehyde method and immunized mouse with
      multifocal intradermal injections. Using a conventional immunization protocol, 12
      stable monoclonal antibodies (MAbs) producing cell lines recognizing
      nitrotyrosine were obtained. Six MAbs were selected for further characterization.
      A study of cross-reactions with nitrotyrosine-like compounds showed that the
      antibodies had a high specificity for nitrotyrosine, but no detectable reactivity
      with L-tyrosine, p-nitro-L-phenylalanine, o-phospho-L-tyrosine or 3-amino-L
      tyrosine. Using these high titer and affinity antibodies, a competitive
      inhibition ELISA was developed with a lower detection limit of approximately 20
      nmol/L to detect both free and protein-bound nitrotyrosine in biological systems.

PMID- 14683608
TI  - Reduced models of the circadian oscillators in Neurospora crassa and Drosophila
      melanogaster illustrate mechanistic similarities.
AB  - We have developed a reduced model representing feedback loops of transcriptional
      regulation underlying circadian rhythms in Neurospora crassa. The model contains
      two delay differential equations that describe the dynamics of two core gene
      products, FRQ and WCC. In a negative feedback loop, FRQ protein represses frq
      transcription by binding the white-collar complex (WCC), which consists of the WC
      1 and WC-2 proteins. In a positive feedback loop, WCC indirectly enhances its own
      formation. The model simulates circadian oscillations, light entrainment, and a
      phase-response curve (PRC) similar to experimental PRCs. The Neurospora model is
      virtually identical to a model describing Drosophila circadian rhythm generation,
      illustrating that rhythm generation in these divergent organisms shares important
      mechanistic elements. Significant dynamic differences were found when the
      parameter spaces of both models were explored to analyze changes in oscillations
      and bifurcations to steady states. Stochastic fluctuations in molecule numbers
      were simulated with the Gillespie algorithm. Circadian oscillations and
      entrainment to light were simulated with <80 molecules of FRQ and WCC present on
      average. Simulations suggest that in both Neurospora and Drosophila, only the
      negative feedback loop is essential for circadian oscillations. Similar models
      may aid understanding of circadian mechanisms in mammals and other organisms.

PMID- 14683609
TI  - Next generation simulation tools: the Systems Biology Workbench and BioSPICE
      integration.
AB  - Researchers in quantitative systems biology make use of a large number of
      different software packages for modelling, analysis, visualization, and general
      data manipulation. In this paper, we describe the Systems Biology Workbench
      (SBW), a software framework that allows heterogeneous application components-
      written in diverse programming languages and running on different platforms--to
      communicate and use each others' capabilities via a fast binary encoded-message
      system. Our goal was to create a simple, high performance, opensource software
      infrastructure which is easy to implement and understand. SBW enables
      applications (potentially running on separate, distributed computers) to
      communicate via a simple network protocol. The interfaces to the system are
      encapsulated in client-side libraries that we provide for different programming
      languages. We describe in this paper the SBW architecture, a selection of current
      modules, including Jarnac, JDesigner, and SBWMeta-tool, and the close integration
      of SBW into BioSPICE, which enables both frameworks to share tools and compliment
      and strengthen each others capabilities.

PMID- 14683610
TI  - Continuous-time identification of gene expression models.
AB  - One objective of systems biology is to create predictive, quantitative models of
      the transcriptional regulation networks that govern numerous cellular processes.
      Gene expression measurements, as provided by microarrays, are commonly used in
      studies that attempt to infer the regulation underlying these processes. At
      present, most gene expression models that have been derived from microarray data
      are based in discrete-time, which have limited applicability to common biological
      data sets, and may impede the integration of gene expression models with other
      models of biological processes that are formulated as ordinary differential
      equations (ODEs). To overcome these difficulties, a continuous-time approach for
      process identification to identify gene expression models based in ODEs was
      developed. The approach utilizes the modulating functions method of parameter
      identification. The method was applied to three simulated systems: (1) a linear
      gene expression model, (2) an autoregulatory gene expression model, and (3)
      simulated microarray data from a nonlinear transcriptional network. In general,
      the approach was well suited for identifying models of gene expression dynamics,
      capable of accurately identifying parameters for small numbers of data samples in
      the presence of modest experimental noise. Additionally, numerous insights about
      gene expression modeling were revealed by the case studies.

PMID- 14683611
TI  - Development and validation of computational models for mammalian circadian
      oscillators.
AB  - Circadian rhythms are endogenous rhythms with a cycle length of approximately 24
      h. Rhythmic production of specific proteins within pacemaker structures is the
      basis for these physiological and behavioral rhythms. Prior work on mathematical
      modeling of molecular circadian oscillators has focused on the fruit fly,
      Drosophila melanogaster. Recently, great advances have been made in our
      understanding of the molecular basis of circadian rhythms in mammals.
      Mathematical models of the mammalian circadian oscillator are needed to piece
      together diverse data, predict experimental results, and help us understand the
      clock as a whole. Our objectives are to develop mathematical models of the
      mammalian circadian oscillator, generate and test predictions from these models,
      gather information on the parameters needed for model development, integrate the
      molecular model with an existing model of the influence of light and rhythmicity
      on human performance, and make models available in BioSpice so that they can be
      easily used by the general community. Two new mammalian models have been
      developed, and experimental data are summarized. These studies have the potential
      to lead to new strategies for resetting the circadian clock. Manipulations of the
      circadian clock can be used to optimize performance by promoting alertness and
      physiological synchronization.

PMID- 14683613
TI  - BioSPICE: access to the most current computational tools for biologists.
AB  - The goal of the BioSPICE program is to create a framework that provides
      biologists access to the most current computational tools. At the program
      midpoint, the BioSPICE member community has produced a software system that
      comprises contributions from approximately 20 participating laboratories
      integrated under the BioSPICE Dashboard and a methodology for continued software
      integration. These contributed software modules are the BioSPICE Dashboard, a
      graphical environment that combines Open Agent Architecture and NetBeans software
      technologies in a coherent, biologist-friendly user interface. The current
      Dashboard permits data sources, models, simulation engines, and output displays
      provided by different investigators and running on different machines to work
      together across a distributed, heterogeneous network. Among several other
      features, the Dashboard enables users to create graphical workflows by
      configuring and connecting available BioSPICE components. Anticipated future
      enhancements to BioSPICE include a notebook capability that will permit
      researchers to browse and compile data to support model building, a biological
      model repository, and tools to support the development, control, and data
      reduction of wet-lab experiments. In addition to the BioSPICE software products,
      a project website supports information exchange and community building.

PMID- 14683612
TI  - Genetic variations in peripheral blood mononuclear cells in piglets used as an
      animal model for staphylococcal enterotoxin exposures.
AB  - We have used piglets as an animal model for studying the toxic effects of
      staphylococcal enterotoxins (SEs). Piglets are easy to handle, easy to carry out
      vital measurements, inexpensive, and more importantly, express remarkably similar
      pathological symptoms and responses to SE intoxication as humans at comparable
      doses. Microarray analyses are used to study the effect of many infections on
      gene expression profile in peripheral blood mononuclear cells. This high
      throughput application offers detailed depiction of alteration at the molecular
      levels. When using high throughput gene expression analysis, there is a high
      possibility of finding genes that vary normally in the tissues under study. It is
      necessary to verify genes that are normally differentially expressed between
      piglets. To evaluate the normal physiological variation in gene expression in
      vivo in piglets, we used cDNA microarray to measure gene expression levels in
      peripheral blood mononuclear cells from 10 normal Yorkshire piglets. We used
      analysis of variance to determine genes that showed statistically significant
      variations across piglets. Out of 1185 genes, 19 (1.6%) genes revealed
      statistically significant variance between RNA samples. Some of these varying
      genes are involved in stress response, immune response, and transcription. This
      study facilitates the characterization of gene expression base line needed for
      meaningful interpretation of microarray data.

PMID- 14683614
TI  - The digital human: towards a unified ontology.

PMID- 14683616
TI  - The problematisation of existence: towards a philosophy of complexity.
AB  - By assuming that the Universe is best described as a cellular automaton, and by
      making use of results from the field of computational mechanics, this paper
      discusses an extension of the notion of existence from a simple binary opposition
      to that of a continuum. It is argued that none of the traditional objects of
      science, or any objects from any discipline, formal or not, can be said to be
      real in any absolute sense though a substantial realism may be associated with
      them. By problematising existence it is proposed that an evolutionary philosophy
      referred to as critical pluralism is more sensitive to the demands of complexity
      than contemporary scientific approaches. Though many of the conclusions reported
      herein are not original, the fact that they can be 'proved' in a scientific
      sense, and explored scientifically, is certainly of interest and is an
      interpretation of complexity theory that has received little attention.

PMID- 14683617
TI  - Transitions between two pictorial attractors.
AB  - Two experiments exploring similarity judgments on pairs and triplets of stimuli
      drawn from pictorial series are described. The stimuli are the Man-Woman and
      Gypsy-Girl pictures that slowly change from one prototype to the other as one
      progresses along the series. These have been used previously to demonstrate
      hysteresis of category judgments on ambiguous figures; the Man Woman series has
      been both modelled as a problem in neural network theory and mapped onto part of
      a cusp catastrophe surface. It. is shown that the transition process is
      complicated with a zone of uncertainty and prevalence of bimodality in many of
      the pairwise similarity judgments. The dynamics are interpreted in terms of
      transitions between two saddle-node attractors that are themselves not a discrete
      pair but have some overlap in their composition.

PMID- 14683618
TI  - Situated learning theory: adding rate and complexity effects via Kauffman's NK
      model.
AB  - For many firms, producing information, knowledge, and enhancing learning
      capability have become the primary basis of competitive advantage. A review of
      organizational learning theory identifies two approaches: (1) those that treat
      symbolic information processing as fundamental to learning, and (2) those that
      view the situated nature of cognition as fundamental. After noting that the
      former is inadequate because it focuses primarily on behavioral and cognitive
      aspects of individual learning, this paper argues the importance of studying
      learning as interactions among people in the context of their environment. It
      contributes to organizational learning in three ways. First, it argues that
      situated learning theory is to be preferred over traditional behavioral and
      cognitive learning theories, because it treats organizations as complex adaptive
      systems rather than mere information processors. Second, it adds rate and
      nonlinear learning effects. Third, following model-centered epistemology, it uses
      an agent-based computational model, in particular a "humanized" version of
      Kauffman's NK model, to study the situated nature of learning. Using simulation
      results, we test eight hypotheses extending situated learning theory in new
      directions. The paper ends with a discussion of possible extensions of the
      current study to better address key issues in situated learning.

PMID- 14683619
TI  - Can a monkey with a computer create art?
AB  - A computer can be programmed to search through the solution of millions of
      equations to find a few hundred whose graphical display is aesthetically pleasing
      to humans. This paper describes some methods for performing such an exhaustive
      search, criteria for automatically judging aesthetic appeal, and examples of the
      results.

PMID- 14683620
TI  - Gene therapy: novel treatments for polyneuropathy and chronic pain.

PMID- 14683622
TI  - Organization of regional and local stroke resources: methods to expedite acute
      management of stroke.
AB  - Proving the efficacy of thrombolysis in improving outcome from stroke has put
      time to assessment of patients at the forefront for healthcare providers when
      organizing stroke care. The chain of recovery begins with the patient. Efforts
      are being made to improve the general public's understanding of stroke. However,
      it appears at the moment that a greater effect in reducing the delay to initial
      medical assessment and treatment decision is to be gained through streamlining
      care as soon as 911 has been called. Emergency medical services dispatchers and
      technicians play a key role in recognizing that a patient is having a stroke and
      prioritizing the transport of the patient to an appropriate facility. Emergency
      departments need to have clear protocols in place to ensure that physicians can
      make prompt treatment decisions after having fully assessed and investigated the
      patient. Only with all these pieces in place is the initial phase of the chain of
      recovery complete, with the end result that more patients have the chance to have
      an improved outcome from stroke.

PMID- 14683623
TI  - Management of patients with stroke and a patent foramen ovale.
AB  - Observational studies have established a strong association between the presence
      of patent foramen ovale (PFO) and increased risk of ischemic stroke. The
      mechanism involved is presumed to be a paradoxical embolism from a venous
      thrombus that travels via the PFO to the systemic circulation. The best treatment
      modality to prevent recurrent stroke in patients with PFO remains undefined.
      There are four major choices: 1) medical therapy with anticoagulants, 2) medical
      therapy with antiplatelet agents, 3) surgical closure, and 4) percutaneous device
      closure. The Patent Foramen Ovale in Cryptogenic Stroke Study has demonstrated
      that antiplatelet and anticoagulant therapies are of equal benefit in preventing
      recurrent neurologic events in stroke patients with a PFO. Medical therapy should
      remain as the initial choice of secondary prophylactic therapy. PFO closure,
      either surgical or percutaneous, may further reduce event rates; however, this
      remains to be demonstrated because no randomized trial to date has compared PFO
      closure with medical therapy.

PMID- 14683624
TI  - Extracranial-intracranial arterial bypass for treatment of occlusion of the
      internal carotid artery.
AB  - Extracranial-intracranial arterial bypass was frequently utilized in the 1970s
      and early 1980s to treat patients with atherosclerotic occlusive carotid arterial
      lesions not amenable to extracranial arterial revascularization procedures. After
      a large randomized trial reported in 1985 that there was no benefit of surgery in
      these patients, the procedure was generally abandoned as a treatment for
      symptomatic atherosclerotic cerebrovascular disease. In the past two decades,
      multiple studies have shown that patients with impaired cerebral hemodynamics
      distal to an occlusive cerebrovascular lesion have a significantly increased risk
      of subsequent stroke. Two new randomized, controlled clinical trials of
      extracranial-intracranial arterial bypass in patients with symptomatic
      atherosclerotic occlusive cerebrovascular disease that are using cerebral
      hemodynamic criteria for patient selection are currently in progress. At the
      present time, extracranial-intracranial arterial bypass should not be performed
      on these patients outside of a clinical trial.

PMID- 14683625
TI  - Understanding stroke recovery and rehabilitation: current and emerging
      approaches.
AB  - Although stroke is the third leading cause of death in the United States, it is
      the significant disability among survivors that has the greatest impact on
      healthcare and society. It is currently accepted that comprehensive
      rehabilitation programs improve outcome following stroke. We are now trying to
      discern which specific therapeutic approaches work and which do not. Years of
      animal research have resulted in a better understanding of what occurs in the
      brain following stroke and how the brain may reorganize in response to treatment.
      Repetitive use of the involved extremities appears key to optimal behavioral
      recovery and optimal brain reorganization. The advent of technology such as
      functional magnetic resonance imaging and transcortical magnetic stimulation has
      allowed the study of brain reorganization following stroke and rehabilitation in
      humans. Certain drugs also appear to influence neuroplasticity after stroke.
      Timing of therapy and drug delivery appears crucial; the optimal "critical
      period" has not yet been clearly identified. New approaches are slow to reach
      widespread adoption. Neural transplantation combined with repetitive training
      approaches produces behavioral recovery in animals and offers hope for the
      future.

PMID- 14683626
TI  - Treatment or prevention of complications of acute ischemic stroke.
AB  - Both neurologic and medical complications influence outcome after stroke. Space
      occupying supratentorial infarcts can cause transtentorial or uncal herniation,
      which leads to death. Treatments aimed at reducing intracranial pressure in
      patients with such infarcts are of unproven value. Mass-producing cerebellar
      infarction may lead to brainstem compression and obstructive hydrocephalus. These
      lesions often are treated surgically. Although anticonvulsants are not indicated
      for prophylaxis, the occurrence of epileptic seizures mandates treatment to
      prevent recurrences. Depression is common in the acute stage of stroke, but is
      probably not more prevalent after stroke than after myocardial infarction.
      Although dysphagia is common, it usually is a transient problem. Patients with a
      decrease of consciousness or brainstem dysfunction usually need tube feeding for
      a certain period of time. Medical complications, such as fever, infections,
      hyperglycemia, cardiac disorders, pressure sores, and deep venous thrombosis, are
      associated with a poor prognosis and should be treated as early as possible.
      Measures to prevent these complications are part of general care. Hypertension is
      very common during the week after stroke and should be treated only in case of
      extremely high values or malignant hypertension. A multidisciplinary approach in
      the stroke unit is necessary to prevent and manage complications in the acute
      phase of stroke.

PMID- 14683627
TI  - Functional imaging of motor recovery after stroke: remaining challenges.
AB  - Stroke is a leading cause of disability in the United States and is likely to
      have an increasing impact on disability worldwide. In order to develop more
      effective rehabilitation techniques, it is critical to understand the mechanisms
      underlying the mature brain's capacity to reorganize and restore neurologic
      function. Over the past decade, functional brain imaging has been a principal
      investigational tool in elucidating mechanisms of stroke recovery. Functional
      imaging studies of motor performance in patients with stroke consistently
      demonstrate areas of brain activation not present in healthy subjects. The role
      of these additional areas in recovery after stroke remains uncertain. This review
      discusses methodologic and theoretical issues that impact on interpreting
      functional imaging studies of motor recovery after stroke.

PMID- 14683629
TI  - Facioscapulohumeral muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is a dominantly inherited muscular
      dystrophy with a distinctive clinical presentation. Despite the identification of
      a causal deletion on chromosome 4q35 over a decade ago, the molecular
      pathophysiology of FSHD remains unclear. The deleted repeats, though clearly
      associated with FSHD, do not contain expressed genes. The FSHD-associated
      deletions must, therefore, influence the expression of one or more genes at a
      distance from the site of the deletion. Recent studies have suggested potential
      mechanisms through which such a distant effect could be mediated.

PMID- 14683630
TI  - Diabetic neuropathy: clinical features, etiology, and therapy.
AB  - Diabetes mellitus is a common cause of peripheral nervous system disorders that
      manifest in a variety of clinical forms, many of which are often misdiagnosed.
      Over the past two decades, our understanding of the pathophysiology of diabetic
      nerve injury has improved remarkably through the elucidation of the important
      roles of the polyol pathway of glucose metabolism, oxidative injury, advanced
      glycosylation end-products, vascular insufficiency, and other mechanisms. A large
      number of clinical treatment trials based upon this abundant scientific data have
      met with limited success, but ongoing and future trials offer promise for more
      dramatic success in treating this common cause of morbidity and mortality in the
      diabetic population.

PMID- 14683631
TI  - Neuromuscular complications in HIV.
AB  - HIV affects many organs of the body, including the nervous system. As a result, a
      series of neurologic complications have created challenges for scientists and
      clinicians alike. Among these, HIV-associated neuropathy and myopathy may occur
      at all stages of the disease process. Of the neuropathies, distal symmetrical
      polyneuropathy is the most common form. The pathogenesis of primary HIV
      neuropathy is unknown. Other types of neuropathy seen in HIV-infected subjects
      include toxic neuropathy, inflammatory demyelinating polyneuropathy, progressive
      polyradiculopathy, and mononeuritis multiplex. In this review, we present the
      clinical manifestations, pathogenesis, diagnosis, and management of different
      types of neuropathy in HIV infection. Myopathy, another complication of HIV, is
      not associated with any particular stage of immunosuppression. Symptoms include
      symmetrical weakness of the proximal muscles in the extremities. Serum creatine
      kinase levels are often moderately elevated. Electromyography and muscle biopsy
      are helpful tests for diagnosis. Treatment of HIV myopathy includes
      corticosteroids, nonsteroidal anti-inflammatory agents, and intravenous
      immunoglobulin.

PMID- 14683632
TI  - Congenital myopathies.
AB  - The congenital myopathies encompass a group of neuromuscular disorders with
      characteristic morphologic abnormalities in skeletal muscle, including nemaline
      myopathy, central core disease, multi-minicore disease, and myotubular myopathy.
      Giant steps have been made in our understanding of the molecular bases of these
      disorders, all of which show remarkable genetic heterogeneity. This review of
      congenital myopathies examines progress in defining clinical diagnostic criteria
      and novel genetic advances that have provided important clues regarding their
      pathogeneses.

PMID- 14683634
TI  - The utility of muscle biopsy.
AB  - Despite major advances in molecular genetics, histopathologic evaluation of
      muscle biopsy specimens continues to provide important diagnostic information in
      patients with suspected muscle diseases and in patients with vasculitic
      neuropathies. Muscle biopsy specimens are used in diagnosing many inherited as
      well as inflammatory and toxic myopathies. Furthermore, the study of muscle
      histopathology can also enhance our understanding of disease pathogenesis.

PMID- 14683635
TI  - Carbon and gold electrodes as electrochemical transducers for DNA hybridisation
      sensors.
AB  - Genosensor technology relying on the use of carbon and gold electrodes is
      reviewed. The key steps of each analytical procedure, namely DNA-probe
      immobilisation, hybridisation, labelling and electrochemical investigation of the
      surface, are discussed in detail with separate sections devoted to label-free and
      newly emerging magnetic assays. Special emphasis has been given to protocols that
      have been used with real DNA samples.

PMID- 14683633
TI  - Spinal muscular atrophy.
AB  - Spinal muscular atrophy is a common genetic disease of the motor neuron
      (frequency of eight cases per 100,000 live births) with a high mortality during
      infancy and no known treatment. Death is caused by severe and progressive
      restrictive lung disease. New information regarding the nature and function of
      the SMN protein and the availability of new pharmacologic agents now make it
      possible to consider clinical trials in this disease. Rehabilitation and proper
      management of medical complications have improved both the quality and duration
      of life for children with spinal muscular atrophy.

PMID- 14683636
TI  - Electrical behavior of polymer hydrogel composed of poly(vinyl alcohol)
      hyaluronic acid in solution.
AB  - Interpenetrating polymer networks (IPN), as polymer hydrogels composed of
      poly(vinyl alcohol) (PVA) and hyaluronic acid (HA), which exhibited electrical
      sensitive behavior were prepared. The swelling behavior of the IPN/HA IPN was
      studied by immersing the gel in various concentrations of aqueous NaCl solutions
      and various pH buffer solutions. The response of the PVA/HA IPN to electric
      fields stimuli was also investigated. When swollen IPN was placed between a pair
      of electrodes, and an electric field applied, it exhibited bending behavior. The
      PVA/HA IPN also displayed stepwise bending behavior, depending on the magnitude
      of the electric stimulus. Also, for use in biosensors application, their bending
      behavior was studied in Hank's solution at pH 7.4.

PMID- 14683637
TI  - Electric chips for rapid detection and quantification of nucleic acids.
AB  - A silicon chip-based electric detector coupled to bead-based sandwich
      hybridization (BBSH) is presented as an approach to perform rapid analysis of
      specific nucleic acids. A microfluidic platform incorporating paramagnetic beads
      with immobilized capture probes is used for the bio-recognition steps. The
      protocol involves simultaneous sandwich hybridization of a single-stranded
      nucleic acid target with the capture probe on the beads and with a detection
      probe in the reaction solution, followed by enzyme labeling of the detection
      probe, enzymatic reaction, and finally, potentiometric measurement of the enzyme
      product at the chip surface. Anti-DIG-alkaline phosphatase conjugate was used for
      the enzyme labeling of the DIG-labeled detection probe. p-Aminophenol phosphate
      (pAPP) was used as a substrate. The enzyme reaction product, p-aminophenol (pAP),
      is oxidized at the anode of the chip to quinoneimine that is reduced back to pAP
      at the cathode. The cycling oxidation and reduction of these compounds result in
      a current producing a characteristic signal that can be related to the
      concentration of the analyte. The performance of the different steps in the assay
      was characterized using in vitro synthesized RNA oligonucleotides and then the
      instrument was used for analysis of 16S rRNA in Escherichia coli extract. The
      assay time depends on the sensitivity required. Artificial RNA target and 16S
      rRNA, in amounts ranging from 10(11) to 10(10) molecules, were assayed within 25
      min and 4 h, respectively.

PMID- 14683638
TI  - Novel biosensor chip for simultaneous detection of DNA-carcinogen adducts with
      low-temperature fluorescence.
AB  - A monoclonal antibody (MAb)-gold biosensor chip with low-temperature laser
      induced fluorescence detection for analysis of DNA-carcinogen adducts is
      described. Optimization of the detection limit, dynamic range, and biosensing
      applicability of the MAb-gold biosensor chip was achieved by: (1) using
      dithiobis(succinimidyl propionate (DSP)) as a protein linker and (2) employing
      recombinant protein A to provide oriented immobilization of the MAbs. The use of
      DSP, which has a short methylene chain length, led to faster protein binding
      kinetics and higher protein surface density than a longer dithiobis(succinimidyl
      undecanoate) (DSU) linker. The incorporation of recombinant protein A increased
      the distance between the oriented MAb-bound analytes and the gold surface. The
      increased distance minimized fluorescence quenching, resulting in about a 10-fold
      increase in the fluorescence signal in comparison with a chip without protein A.
      The improved chip architecture was used to demonstrate that biosensing of two
      structurally similar benzo[a]pyrene (BP)-derived DNA adducts, BP-6-N7Gua and BP
      diolepoxide-10-N2dG, bound to two specific MAbs immobilized from a mixture at the
      same address on the chip, is feasible. These mutagenic adducts are formed by one
      electron oxidation and monooxygenation pathways, and are depurinating and stable
      DNA adducts, respectively. It is shown that the DNA adducts can be easily
      identified at the same address using time-resolved, low-temperature laser-based
      fluorescence spectroscopy. The current limit of detection is in the low femtomole
      range. These results indicate that a single biosensor chip consisting of a
      Au/DSP/protein A/MAb nano-assembly, with analyte-specific MAbs and low
      temperature fluorescence detection should be suitable for simultaneous detection
      and quantitation of the above adducts, as well as the luminescent antigens for
      which selective MAbs exist.

PMID- 14683640
TI  - A self-assembled monolayer-based piezoelectric immunosensor for rapid detection
      of Escherichia coli O157:H7.
AB  - A piezoelectric immunosensor was developed for rapid detection of Escherichia
      coli O157:H7. It was based on the immobilization of affinity-purified antibodies
      onto a monolayer of 16-mercaptohexadecanoic acid (MHDA), a long-chain carboxylic
      acid-terminating alkanethiol, self-assembled on an AT-cut quartz crystal's Au
      electrode surface with N-hydroxysuccinimide (NHS) ester as a reactive
      intermediate. The binding of target bacteria onto the immobilized antibodies
      decreased the sensor's resonant frequency, and the frequency shift was correlated
      to the bacterial concentration. The stepwise assembly of the immunosensor was
      characterized by means of both quartz crystal microbalance (QCM) and cyclic
      voltammetry techniques. Three analytical procedures, namely immersion, dip-and
      dry and flow-through methods, were investigated. The immunosensor could detect
      the target bacteria in a range of 10(3)-10(8)CFU/ml within 30-50 min, and the
      sensor-to-sensor reproducibility obtained at 10(3) and 10(5) colony-forming units
      (CFU)/ml was 18 and 11% R.S.D., respectively. The proposed sensor was comparable
      to Protein A-based piezoelectric immunosensor in terms of the amount of
      immobilized antibodies and detection sensitivity.

PMID- 14683639
TI  - Amperometric determination of laminarin using immobilized beta-1,3-glucanase.
AB  - A novel sensor system equipped with a reactor packed with beads containing
      immobilized beta-1,3-glucanase and glucose oxidase was developed for the
      amperometric determination of laminarin concentration. The proposed sensor system
      consisted of a reactor, an oxygen electrode, a flow cell, a pump, a buffer tank,
      and a recorder. The measurement was performed with a flow injection system. The
      optimum conditions for the sensor system were as follows: transfer solution, pH
      7.0; 0.1 M phosphate buffer solution; flow rate, 0.15 ml/min; and sample volume,
      50 microl. The response was correlated to the laminarin concentration. The
      calibration curve was obtained between 50 and 0.5 mg/ml laminarin (R2 = 0.994).
      The detection limit was 50 microg/ml laminarin (the ratio of signal/noise = 3).
      The relative standard deviations were 2.0% (n = 15) and 2.5% (n = 15) for 0.4 and
      1.0 mg/ml laminarin solutions, respectively. One assay was completed within 5
      min. Results suggest that the sensor can be used not only for the analysis of
      seaweed and health-enhancing foods but also for monitoring the initial pollution
      of the marine environment.

PMID- 14683641
TI  - Application of impedance spectroscopy for monitoring colloid Au-enhanced antibody
      immobilization and antibody-antigen reactions.
AB  - We used colloidal Au to enhance the amount of antibody immobilized on a gold
      electrode and ultimately monitored the interaction of antigen-antibody by
      impedance measurement. Self-assembly of 6 nm (diameter) colloidal Au onto the
      self-assembled monolayers (SAMs) of 4-aminothiophenol modified gold electrode
      resulted in an easier attachment of antibody. The redox reactions of [Fe(CN)6](4
      )/[Fe(CN)6](3-) on the gold surface were blocked due to the procedures of self
      assembly of 4-aminothiophenol and antibody immobilization, which were
      investigated by cyclic voltammetry and impedance spectroscopy. The interaction of
      antigen with grafted antibody recognition layers was carried out by soaking the
      modified electrode into a phosphate buffer at pH 7.4 with various concentrations
      of antigen at 37 degrees C for 30 min. The antibody recognition layers and their
      interactions with various concentrations of antigen could be detected by
      measurements of the impedance change. The results show that this method has good
      correlation for detection of Hepatitis B virus surface antigen in the range of
      0.5-200 microg/l and a detection limit of about 50 ng/l.

PMID- 14683642
TI  - Bioelectrical impedance assay to monitor changes in cell shape during apoptosis.
AB  - Apoptosis is a strictly regulated and genetically encoded cell 'suicide' that may
      be triggered by cytokines, depletion of growth factors or certain chemicals. It
      is morphologically characterized by severe alterations in cell shape like cell
      shrinkage and disintegration of cell-cell contacts. We applied a non-invasive
      electrochemical technique referred to as electric cell-substrate impedance
      sensing (ECIS) in order to monitor the apoptosis-induced changes in cell shape in
      an integral and quantitative fashion with a time resolution in the order of
      minutes. In ECIS the cells are grown directly on the surface of small gold-film
      electrodes (d = 2 mm). From readings of the electrical impedance of the cell
      covered electrode, performed with non-invasive, low amplitude sensing voltages,
      it is possible to deduce alterations in cell-cell and cell-substrate contacts. To
      improve the sensitivity of this impedance assay we used endothelial cells derived
      from cerebral micro-vessels as cellular model systems since these are well known
      to express electrically tight intercellular junctions. Apoptosis was induced by
      cycloheximide (CHX) and verified by biochemical and cytological assays. The time
      course of cell shape changes was followed with unprecedented time resolution by
      impedance readings at 1 kHz and correlated with biochemical parameters. From
      impedance readings along a broad frequency range of 1-10(6) Hz we could assign
      the observed impedance changes to alterations on the subcellular level. We
      observed that disassembly of barrier-forming tight junctions precedes changes in
      cell-substrate contacts and correlates strongly with the time course of protease
      activation.

PMID- 14683643
TI  - Miniaturized pH biosensors based on electrochemically modified electrodes with
      biocompatible polymers.
AB  - Potentiometric pH sensors based on linear polyethylenimine (L-PEI) and linear
      polypropylenimine(L-PPI), two synthetic enzymes and biocompatible polymers, films
      were prepared by electropolymerization of three different monomers:
      ethylenediamine (EDA), 1,3-diaminopropane (1,3-DAP) and diethylenetriamine (DETA)
      in order to be used in clinical, dermatological and biological applications, such
      as in vivo analysis. In a first step a biosensor was tested which consisted in a
      platinum wire protruded from glass sheath. The polymer film coated on these
      platinum electrodes showed good linear potentiometric responses to pH changes
      from pH 3 to 10. Resulting electrodes present both good reversibility and good
      stability versus time. The effect of the different polymer film thicknesses to
      potentiometric responses was also studied. This study allowed us to develop a
      miniaturized pH biosensor in the second step. This sensor was fabricated using
      photo-lithography, followed by sputtering and lift-off processes, and it included
      an electronic detection system. We have also successfully studied the
      potentiometric responses to pH changes of this device over a period of 1 month,
      and so we propose this new pH micro-biosensor as an alternative to classical pH
      sensors currently used in dermatology.

PMID- 14683644
TI  - Continuous determination of biochemical oxygen demand using microbial fuel cell
      type biosensor.
AB  - A mediator-less microbial fuel cell (MFC) was used as a biochemical oxygen demand
      (BOD) sensor in an amperometric mode for real-time wastewater monitoring. At a
      hydraulic retention time of 1.05 h, BOD values of up to 100 mg/l were measured
      based on a linear relationship, while higher BOD values were measured using a
      lower feeding rate. About 60 min was required to reach a new steady-state current
      after the MFCs had been fed with different strength artificial wastewaters (Aws).
      The current generated from the MFCs fed with AW with a BOD of 100 mg/l was
      compared to determine the repeatability, and the difference was less than 10%.
      When the MFC was starved, the original current value was regained with a varying
      recovery time depending on the length of the starvation. During starvation, the
      MFC generated a background level current, probably due to an endogenous
      metabolism.

PMID- 14683645
TI  - First results on label-free detection of DNA and protein molecules using a novel
      integrated sensor technology based on gravimetric detection principles.
AB  - A novel integrated bio-sensor technology based on thin-film bulk acoustic wave
      resonators on silicon is presented and the feasibility of detecting DNA and
      protein molecules proofed. The detection principle of these sensors is label-free
      and relies on a resonance frequency shift caused by mass loading of an acoustic
      resonator, a principle very well known from quartz crystal micro balances.
      Integrated ZnO bulk acoustic wave resonators with resonance frequencies around 2
      GHz have been fabricated, employing an acoustic mirror for isolation from the
      silicon substrate. DNA oligos have been thiol-coupled to the gold electrode by on
      wafer dispensing. In a further step, samples have either been hybridised or
      alternatively a protein has been coupled to the receptor. The measurement results
      show the new bio-sensor being capable of both, detecting proteins as well as the
      DNA hybridisation without using a label. Due to the substantially higher
      oscillation frequency, these sensors already show much higher sensitivity and
      resolution comparable to quartz crystal micro balances. The potential for these
      sensors and sensors arrays as well as technological challenges will be discussed
      in detail.

PMID- 14683646
TI  - Enhancement of stability of immobilized glucose oxidase by modification of free
      thiols generated by reducing disulfide bonds and using additives.
AB  - Stability of glucose oxidase (GOD) immobilized with lysozyme has been
      considerably enhanced by modification of free thiols generated by reducing
      disulfide bonds using beta-mercaptoethanol and N-ethylmaleimide in conjunction
      with additives like antibiotics and salts. Thermal stability of immobilized GOD
      was quantified by means of the transition temperature, Tm and the operational
      stability by half-life t1/2 at 70 degrees C. Modification of the free thiols in
      the enzyme coupled with the presence of kanamycin, NaCl, and K2SO4, led to
      increase in Tm, to 80, 82 and 84 degrees C (compared to 75 degrees C in control)
      and t1/2 by 7.7-, 11- and 22-fold, respectively, indicating that this method can
      be effectively used for enhancing the stability of enzymes.

PMID- 14683647
TI  - Pulse mode shear horizontal-surface acoustic wave (SH-SAW) system for liquid
      based sensing applications.
AB  - In this work, we describe a novel pulse mode shear horizontal-surface acoustic
      wave (SH-SAW) polymer coated biosensor that monitors rapid changes in both
      amplitude and phase. The SH-SAW sensors were fabricated on 36 degrees rotated Y
      cut X propagating lithium tantalate (36 YX.LT). The sensitivity of the device to
      both mass loading and visco-elastic effects may be increased by using a thin
      guiding layer of cross-linked polymer. Two acoustic modes are excited by the
      electrodes in this crystalline direction. Metallisation of the propagation path
      of the 36 YX.LT devices allows the two modes to be discriminated. Successive
      polymer coatings resulted in the observation of resonant conditions in both modes
      as the layer thickness was increased. Using the 36 YX.LT devices, we have
      investigated the application of a novel pulse mode system by sensing a sequence
      of deposition and removal of a biological layer consisting of vesicles of the
      phospholipid POPC. A continuous wave system was used to verify the accuracy of
      the pulse mode system by sensing a series of poly(ethylene glycol) (PEG)
      solutions. The data clearly demonstrates the ability of the 36 YX.LT pulse mode
      system to provide rapid measurements of both amplitude and phase for biosensing
      applications.

PMID- 14683648
TI  - Wanted: help through the jungle of hospital care.

PMID- 14683649
TI  - Paediatric acute heart failure--from deck chairs to lifeboats.

PMID- 14683650
TI  - Atherosclerosis: infection-induced involvement of mitochondrial chaperonins.

PMID- 14683651
TI  - Hypothermia for traumatic brain injury: how soon, how cold, and how long?

PMID- 14683652
TI  - What can we learn from developmental studies of psychiatric disorders?

PMID- 14683653
TI  - Treatment of Ebola virus infection with a recombinant inhibitor of factor
      VIIa/tissue factor: a study in rhesus monkeys.
AB  - BACKGROUND: Infection with the Ebola virus induces overexpression of the
      procoagulant tissue factor in primate monocytes and macrophages, suggesting that
      inhibition of the tissue-factor pathway could ameliorate the effects of Ebola
      haemorrhagic fever. Here, we tested the notion that blockade of fVIIa/tissue
      factor is beneficial after infection with Ebola virus. METHODS: We used a rhesus
      macaque model of Ebola haemorrhagic fever, which produces near 100% mortality. We
      administered recombinant nematode anticoagulant protein c2 (rNAPc2), a potent
      inhibitor of tissue factor-initiated blood coagulation, to the macaques either 10
      min (n=6) or 24 h (n=3) after a high-dose lethal injection of Ebola virus. Three
      animals served as untreated Ebola virus-positive controls. Historical controls
      were also used in some analyses. FINDINGS: Both treatment regimens prolonged
      survival time, with a 33% survival rate in each treatment group. Survivors are
      still alive and healthy after 9 months. All but one of the 17 controls died. The
      mean survival for the six rNAPc2-treated macaques that died was 11.7 days
      compared with 8.3 days for untreated controls (p=0.0184). rNAPc2 attenuated the
      coagulation response as evidenced by modulation of various important coagulation
      factors, including plasma D dimers, which were reduced in nearly all treated
      animals; less prominent fibrin deposits and intravascular thromboemboli were
      observed in tissues of some animals that succumbed to Ebola virus. Furthermore,
      rNAPc2 attenuated the proinflammatory response with lower plasma concentrations
      of interleukin 6 and monocyte chemoattractant protein-1 (MCP-1) noted in the
      treated than in the untreated macaques. INTERPRETATION: Post-exposure protection
      with rNAPc2 against Ebola virus in primates provides a new foundation for
      therapeutic regimens that target the disease process rather than viral
      replication.

PMID- 14683654
TI  - Cavernous sinus thrombosis.

PMID- 14683655
TI  - Safety and antigenicity of whole virus and subunit influenza A/Hong Kong/1073/99
      (H9N2) vaccine in healthy adults: phase I randomised trial.
AB  - BACKGROUND: In 1999, avian influenza A/Hong Kong/1073/99 (H9N2) virus emerged as
      a pandemic threat to human beings. We aimed to assess safety, tolerability, and
      antigenicity of whole virus and subunit H9N2 vaccines in healthy volunteers.
      METHODS: In a phase I randomised trial we randomly assigned 60 participants to
      whole virus or subunit H9N2 vaccine. Two doses of 7.5 microg, 15 microg, or 30
      microg haemagglutinin influenza A H9N2 vaccine, were given 3 weeks apart. We
      measured antibody responses by haemagglutination-inhibition and
      microneutralisation. The primary outcome was geometric mean antibody titre 21
      days after vaccination. Analysis was per protocol. FINDINGS: Both vaccines were
      safe and well tolerated. The antibody titres after vaccination did not differ
      significantly between subunit and whole virus vaccine. 24 of 60 prevaccination
      serum samples had unexpected reactivity to H9N2, but only in participants older
      than 32 years, in whom one dose of either vaccine evoked antibody responses
      associated with protection. In participants aged 32 years or younger, antibody
      responses to one dose of whole virus or subunit vaccine were poor, fulfilling
      none of the criteria used for yearly relicensing of interpandemic vaccines. Whole
      virus vaccine produced a significantly higher probability of seroconversion
      compared with subunit virus for this age-group. INTERPRETATION: In
      immunologically naive patients whole-virus vaccine produced better responses than
      subunit vaccine. Two doses of subunit or whole virus vaccine would leave a large
      proportion of the naive population (< or =32 years) unprotected against A/Hong
      Kong/1073/99 (H9N2). Primed patients should be protected with a single dose of
      either vaccine.

PMID- 14683656
TI  - The waiting game: bridging to paediatric heart transplantation.
AB  - BACKGROUND: Although mechanical circulatory support might not increase the number
      of adults surviving to transplantation, because of the shortage of donor organs,
      the situation might be different for children. Our aim was to assess the effect
      of mechanical assist devices to bridge children with end-stage cardiomyopathy to
      heart transplantation. METHODS: A 5-year retrospective review was undertaken with
      data from the UK paediatric transplant programme and from bridging to transplant
      done at two paediatric transplant centres in the UK. FINDINGS: Between Jan 1,
      1998 and Dec 31, 2002, 22 children with end-stage cardiomyopathy, median age 5.7
      years (range 1.2-17), were supported by a mechanical assist device as a bridge to
      first heart transplantation, with a 77% survival rate to hospital discharge. Nine
      were supported by a paracorporeal ventricular assist device, six received
      transplantation, five survived to discharge (55%), with one late death. 13 were
      supported by extra-corporeal membrane oxygenation, and 12 were transplanted and
      survived to discharge (92%) with one late death. With urgent listing, the median
      waiting time for a heart was 7.5 days (range 1.5-22 days). The correlation
      between the proportion of patients bridged to transplantation and the proportion
      of patients dying while on the transplant waiting list was r=-0.93, p=0.02.
      INTERPRETATION: Our findings lend support to the hypothesis that a national
      mechanical assist programme to bridge children to transplantation can minimise
      the number dying while on the heart transplant waiting list. In the context of
      urgent listing and a short waiting time, extra-corporeal membrane oxygenation
      seems to provide the safest form of support.

PMID- 14683657
TI  - Interaction of antibodies against cytomegalovirus with heat-shock protein 60 in
      pathogenesis of atherosclerosis.
AB  - BACKGROUND: Infections and autoimmunity have been implicated in the pathogenesis
      of atherosclerosis. Cytomegalovirus has been shown to contribute to the disease.
      Autoantibodies against human heat-shock protein (HSP) 60 are present in most
      atherosclerotic patients, and their titre correlates with disease severity,
      suggesting that anti-HSP60 might be implicated in disease pathogenesis. We
      postulated that cytomegalovirus infection might induce antibodies able to bind
      human HSP60 and to cause endothelial-cell damage. METHODS: We studied 180
      patients with coronary-artery disease, raised high sensitivity C-reactive protein
      concentrations, and presence or absence of traditional risk factors; 90 patients
      with coronary-artery disease, normal values for high sensitivity C-reactive
      protein, and no traditional risk factors; and 98 controls. Individual sera were
      used to define the relevant epitope of HSP60 by ELISA. Affinity purified IgGs
      were used to identify endothelial cell-surface ligands by western blot and to
      induce apoptotic cell death. FINDINGS: We identified an 11 aminoacid sequence of
      HSP60 that was recognised by most patients with coronary-artery disease. This
      peptide shares homology with cytomegalovirus-derived proteins UL122 and US28. The
      same patients' sera recognised UL122-derived and US28-derived peptides. Purified
      IgGs against HSP60 and the viral peptides bound non-stressed human endothelial
      cells and induced endothelial-cell apoptosis by interaction with cell-surface
      molecules. INTERPRETATION: During cytomegalovirus infection, antibodies against
      the virus can arise that are able to crossreact with human HSP60 and cause
      apoptosis of non-stressed endothelial cells, which is judged a primary event in
      the pathogenesis of atherosclerosis.

PMID- 14683658
TI  - A blurred view from Everest.

PMID- 14683659
TI  - Change to abacavir-lamivudine-tenofovir combination treatment in patients with
      HIV-1 who had complete virological suppression.
AB  - Patients who have not received previous antiretroviral treatment (ART) have a
      high failure rate on the combination treatment of abacavir, lamivudine, and
      tenovir. We assessed the virological failure rate in eight patients with HIV-1
      who switched to this combination after having complete virological suppression
      from their previous long-term ART (median 8.0 months, range 7.5-18.0). Five of
      the eight patients showed virological failure. Four of these five patients had
      either the K65R mutation, the M184V/I mutation, or both. This combination of
      drugs cannot therefore be recommended as alternative treatment in patients with
      HIV-1 who are fully virologically suppressed.

PMID- 14683660
TI  - HIV-1 seroprevalence rates in women and relinquishment of infants to the state in
      St Petersburg, Russia, 2002.
AB  - The effectiveness of rapid HIV-1 testing and nevirapine prophylaxis for HIV
      infected mothers without prenatal care has been shown. We found that from 1998 to
      2002, HIV-1 seroprevalence in women giving birth in St Petersburg, Russia
      increased 100-fold: from 0.013% to 1.3% (p<0.0001). HIV-1 seroprevalence was 8%
      (114 of 1466) in women without prenatal care and 1% (376 of 37645) in those with
      prenatal care (p<0.0001). All 376 HIV-1-infected women with, and 41% (47 of 114)
      of HIV-1-infected women without prenatal care received intrapartum antiretroviral
      therapy (p<0.0001). In women who were HIV-1 positive, 26% (30 of 114) of those
      without prenatal care and 4% (13 of 371) of those with prenatal care relinquished
      their infants to the custody of the state, compared with 1% (354 of 37 621) of
      HIV-1-negative women (p<0.0001).

PMID- 14683661
TI  - Community-acquired pneumonia.
AB  - This seminar reviews important features and management issues of community
      acquired pneumonia (CAP) that are especially relevant to immunocompetent adults
      in light of new information about cause, clinical course, diagnostic testing,
      treatment, and prevention. Streptococcus pneumoniae remains the most important
      pathogen; however, emerging resistance of this organism to antimicrobial agents
      has affected empirical treatment of CAP. Atypical pathogens have been quite
      commonly identified in several prospective studies. The clinical significance of
      these pathogens (with the exception of Legionella spp) is not clear, partly
      because of the lack of rapid, standardised tests. Diagnostic evaluation of CAP is
      important for appropriate assessment of severity of illness and for establishment
      of the causative agent in the disease. Until better rapid diagnostic methods are
      developed, most patients will be treated empirically. Antimicrobials continue to
      be the mainstay of treatment, and decisions about specific agents are guided by
      several considerations that include spectrum of activity, and pharmacokinetic and
      pharmacodynamic principles. Several factors have been shown to be associated with
      a beneficial clinical outcome in patients with CAP. These factors include
      administration of antimicrobials in a timely manner, choice of antibiotic
      therapy, and the use of a critical pneumonia pathway. The appropriate use of
      vaccines against pneumococcal disease and influenza should be encouraged. Several
      guidelines for management of CAP have recently been published, the
      recommendations of which are reviewed.

PMID- 14683662
TI  - Treatment of antiretroviral-drug-resistant HIV-1 infection.
AB  - Drug-resistant HIV-1 is a cause of growing clinical and public-health concern. In
      many patients, combination antiretroviral therapy fails to achieve complete viral
      suppression (virological failure). Continuing viral replication during therapy
      leads to the accumulation of drug-resistance mutations, resulting in increased
      viral load and a greater risk of disease progression. Patients with drug
      resistant HIV-1 infection have three therapeutic options: a change to a salvage
      regimen with the aim of fully suppressing viral replication; interruption of
      therapy; or continuation of a partially effective regimen. The first strategy is
      preferred for most patients failing their first or perhaps their second regimen.
      However, the best approach remains unclear for patients who have failed multiple
      treatment regimens and who have limited options for complete viral suppression.
      The management of such patients requires a careful understanding of the
      pathogenesis of drug-resistant HIV-1, the clinical consequences of virological
      failure, the potential benefits and limitations of diagnostic assays, and the
      likelihood that agents in development will be effective.

PMID- 14683663
TI  - Medical consensus and informed consent: the patient needs more time.

PMID- 14683664
TI  - Crohn's disease: the cold chain hypothesis.
AB  - Crohn's disease is the result of an abnormal immune response of the gut mucosa
      triggered by one or more environmental risk factors in people with predisposing
      gene variations, including CARD15 mutations. Epidemiological data allow
      assessment of familial environmental risk factors related to western lifestyle,
      diet, bacteria, and domestic hygiene. All findings point to refrigeration as a
      potential risk factor for Crohn's disease. Furthermore, cold-chain development
      paralleled the outbreak of Crohn's disease during the 20th century. The cold
      chain hypothesis suggests that psychrotrophic bacteria such as Yersinia spp and
      Listeria spp contribute to the disease. These bacteria have been identified in
      Crohn's disease lesions and we discuss their pathogenic properties with respect
      to our knowledge of the disease. From a molecular perspective, we postulate that
      the disease is a result of a defect in host recognition by pathogenic bacterial
      components that usually escape the immune response (eg, Yop molecules), which
      results in an excessive host response to these bacteria.

PMID- 14683665
TI  - Does informed consent to research require comprehension?

PMID- 14683666
TI  - Physical examination.

PMID- 14683667
TI  - The lonely world of the inpatient family.

PMID- 14683668
TI  - Physical examination.

PMID- 14683669
TI  - Physical examination.

PMID- 14683670
TI  - Physical examination.

PMID- 14683672
TI  - Influenza vaccine and FDG-PET.

PMID- 14683674
TI  - Treatment of severe acute respiratory syndrome in health-care workers.

PMID- 14683675
TI  - Culture and medical terms: help or headache?

PMID- 14683676
TI  - Cardiovascular protection in haemophilia.

PMID- 14683677
TI  - Availability of SARS information in Japan.

PMID- 14683683
TI  - Hippatitis rex.

PMID- 14683686
TI  - Phospholipase A2 isozymes in pregnancy and parturition.
AB  - Mammalian cells contain several structurally different phospholipase (PLA2)
      enzymes that exhibit distinct localisation, function and mechanisms of
      regulation. PLA2 isozymes have been postulated to play significant roles in the
      parturition process. Both secretory and cytosolic PLA2 isozymes have been
      identified in human gestational tissues, and there is differential expression of
      these PLA2 isozymes in human fetal membranes and placenta obtained at preterm and
      term. The aims of this commentary are: (1) to review recent data concerning the
      expression, role and regulation of PLA2 isozymes in human gestational tissues;
      and (2) to present novel data demonstrating the regulation of PLA2 isozymes in
      human gestational tissues by nuclear factor-kappa B (NF-kappaB) and peroxisome
      proliferator-activated receptor (PPAR)-g.

PMID- 14683687
TI  - Prostaglandin synthases: recent developments and a novel hypothesis.
AB  - Cells are continuously exposed to cues, which signal cell survival or death. Fine
      tuning of these conflicting signals is essential for tissue development and
      homeostasis, and defective pathways are linked to many disease processes,
      especially cancer. It is well established that prostaglandins (PGs), as
      signalling molecules, are important regulators of cell proliferation,
      differentiation and apoptosis. PG production has been a focus of many researchers
      interested in the mechanisms of parturition. Previously, investigators have
      focussed on the committed step of PG biosynthesis, the conversion by
      prostaglandin H synthase (PGHS; also termed cyclo-oxygenase, COX) of arachidonic
      acid (AA) (substrate) to PGH2, the common precursor for biosynthesis of the
      various prostanoids. However, recently the genes encoding the terminal synthase
      enzymes involved in converting PGH2 to each of the bioactive PGs, including the
      major uterotonic PGs, PGE2 (PGE synthase) and PGF2alpha (PGF synthase), have been
      cloned and characterized. This review highlights how the regulation of the
      expression and balance of key enzymes can produce, from a single precursor,
      prostanoids with varied and often opposing effects.

PMID- 14683689
TI  - Expression, localization and function of prostaglandin receptors in myometrium.
AB  - Prostaglandins (PGs) play a role in the initiation and maintenance of labor,
      acting via specific relaxatory or contractile receptors on myometrium. Myometrial
      response to addition of PGs may be determined by the type and concentration of
      receptor expressed. Autoradiographic and ligand binding studies suggest a
      topographic distribution of receptors between fundus, lower segment, and cervix,
      and that hormonally regulated changes in expression occur with advancing
      gestation and labor. These receptors have now been cloned and sequenced allowing
      molecular studies. Current dogma suggests functional regionalization of the
      pregnant human uterus occurs with the lower segment displaying a contractile
      phenotype throughout gestation changing to a relaxatory phenotype at labor to
      allow passage of the fetal head whereas the upper segment has a relaxatory
      phenotype throughout most of gestation to accommodate the growing fetus and
      adopts a contractile phenotype for expulsion at labor. Studies to determine the
      role of PG receptors in this phenomenon are currently underway.

PMID- 14683688
TI  - Transcriptional regulation of genes for enzymes of the prostaglandin biosynthetic
      pathway.
AB  - Numerous studies over the years have demonstrated changes in prostaglandin (PG)
      levels in intrauterine tissues in association with labour, and PG administration
      has long been used to induce delivery. While it is now widely accepted that PGs
      play a major role in human parturition, the complex regulation of their levels is
      still being elucidated, with the focus on the transcriptional control of the
      enzymes responsible for the various steps in PG biosynthesis and catabolism.

PMID- 14683690
TI  - Nuclear prostaglandin receptors: role in pregnancy and parturition?
AB  - The key regulatory role of prostanoids [prostaglandins (PGs) and thromboxanes
      (TXs)] in the maintenance of pregnancy and initiation of parturition has been
      established. However, our understanding of how these events are fine-tuned by the
      recruitment of specific signaling pathways remains unclear. Whereas, initial
      thoughts were that PGs were lipophilic and would easily cross cell membranes
      without specific receptors or transport processes, it has since been realized
      that PG signaling occurs via specific cell surface G-protein coupled receptors
      (GPCRs) coupled to classical adenylate cyclase or inositol phosphate signaling
      pathways. Furthermore, specific PG transporters have been identified and cloned
      adding a further level of complexity to the regulation of paracrine action of
      these potent bioactive molecules. It is now apparent that PGs also activate
      nuclear receptors, opening the possibility of novel intracrine signaling
      mechanisms. The existence of intracrine signaling pathways is further supported
      by accumulating evidence linking the perinuclear localization of PG synthesizing
      enzymes with intracellular PG synthesis. This review will focus on the evidence
      for a role of nuclear actions of PGs in the regulation of pregnancy and
      parturition.

PMID- 14683691
TI  - Prostaglandin endoperoxide H synthase inhibitors and other tocolytics in preterm
      labour.
AB  - Preterm delivery (<37 weeks of gestation) is the major obstetrical complication
      in developed countries, yet attempts to delay labour and prolong pregnancy have
      largely been unsuccessful. One of the many reasons it is so difficult to prevent
      preterm birth is that the nature of preterm labour changes as a function of
      gestational age, maternal lifestyle factors or infection, to list a few of the
      reasons. The inhibitors of prostaglandin endoperoxide H synthase (PGHS), known as
      the Non-steroidal Antiinflammatory Drugs, have been viewed with interest as
      tocolytics with promising effectiveness under most conditions of preterm labour.
      Three isoforms of PGHS exist; the first two, PGHS-1 and -2, have been studied for
      their catalytic activity, X-ray crystallographic structure, and physiological
      roles in the adult and the foetus. Mixed inhibitors and isoform-specific
      inhibitors of PGHS have been developed, and their roles in delaying preterm
      labour are examined and compared to other tocolytics.

PMID- 14683692
TI  - Cannabis, cannabinoids and reproduction.
AB  - In most countries Cannabis is the most widely used illegal drug. Its use during
      pregnancy in developed nations is estimated to be approximately 10%. Recent
      evidence suggests that the endogenous cannabinoid system, now consisting of two
      receptors and multiple endocannabinoid ligands, may also play an important role
      in the maintenance and regulation of early pregnancy and fertility. The purpose
      of this review is therefore twofold, to examine the impact that cannabis use may
      have on fertility and reproduction, and to review the potential role of the
      endocannabinoid system in hormonal regulation, embryo implantation and
      maintenance of pregnancy.

PMID- 14683693
TI  - Topographical specialization of prostaglandin function in late pregnancy and at
      parturition in the baboon.
AB  - Prostaglandins play key central roles in both the maintenance of pregnancy and
      parturition. Extensive data exist from studies in human pregnancy but the needs
      of clinical management and the inability to conduct carefully controlled
      perturbation studies in human pregnancy make it necessary to obtain information
      from nonhuman primate models. We have used the pregnant baboon to evaluate
      production, metabolism and receptor mediated actions of prostaglandins in late
      gestation to demonstrate that expression of key genes is tightly controlled in
      enzyme-specific, gestation age-specific, tissue-specific and uterine region
      specific fashion.

PMID- 14683694
TI  - Prostaglandins and the myometrium and cervix.
AB  - Prostaglandins have long been thought to play important roles in the mechanism of
      parturition. Here we review the involvement of prostaglandins in myometrial and
      cervical functions with emphasis on human labor and birth. In addition, the
      cellular sources of prostaglandins as well as their interactions with various
      other endocrine, paracrine and physical factors, such as oxytocin, corticotropin
      releasing hormone, nitric oxide, platelet activating factor, cytokines,
      endothelin and stretch are also addressed together with their potential role in
      the molecular reorganization of cervical structure associated with labor and
      delivery. Finally, the premier role of progesterone in pregnancy maintenance and
      parturition is juxtaposed with the proposed "fine-tuning", modulatory role of
      prostaglandins and the above listed factors in the regulation of parturition.

PMID- 14683695
TI  - Eicosanoids in preeclampsia.
AB  - Preeclampsia is characterized by an imbalance between two cyclooxygenase
      metabolites of arachidonic acid, thromboxane and prostacyclin, that favors
      thromboxane. Because of the biologic actions of these two eicosanoids, this
      imbalance might explain major clinical symptoms of preeclampsia, such as
      hypertension, platelet aggregation and reduced uteroplacental blood flow. In the
      maternal circulation, this imbalance is primarily manifested by decreased
      production of prostacyclin by endothelial cells. Platelet thromboxane synthesis
      is only increased in severe preeclampsia. In the placenta and in leukocytes, the
      imbalance is exacerbated by increased production of thromboxane coupled with
      decreased production of prostacyclin in both mild and severe preeclampsia.
      Longitudinal measurements of urinary metabolites of thromboxane and prostacyclin
      reveal that the thromboxane/prostacyclin imbalance predates the onset of clinical
      symptoms of preeclampsia. The imbalance between thromboxane and prostacyclin is
      most likely caused by oxidative stress, which is manifest in preeclampsia by
      increased lipid peroxidation and decreased antioxidant protection. Oxidative
      stress may drive this imbalance because lipid peroxides activate the
      cyclooxygenase enzyme to increase thromboxane synthesis, but at the same time
      they inhibit prostacyclin synthase to decrease prostacyclin synthesis. Low-dose
      aspirin therapy (50-150 mg/day) has been considered for the prevention of
      preeclampsia because it selectively inhibits thromboxane synthesis. Several
      studies reported dramatic decreases in the incidence of preeclampsia with low
      dose aspirin therapy. However, two large multicenter studies reported only modest
      decreases, which dampened enthusiasm. The two large studies were "intent to
      treat" studies which included patients who were noncompliant and who discontinued
      the use of aspirin. In one of the studies for which compliance statistics were
      available only 53% of the aspirin group had a compliance rate greater than 75%,
      which raises a question as to whether the effectiveness of aspirin was being
      tested. Low-dose aspirin therapy should not yet be dismissed for the prevention
      of preeclampsia, but be reconsidered with emphasis on compliance using doses of
      aspirin in the range of 100-150 mg/day combined with antioxidants.

PMID- 14683696
TI  - The role of dominant premotor cortex in language: a study using intraoperative
      functional mapping in awake patients.
AB  - Although the role of the premotor cortex (PMC) was widely studied in motor
      function, very few data are currently available about the participation of this
      structure in language. We report a series of 25 right-handed patients harboring a
      low-grade glioma near or within the left dominant PMC, operated on under local
      anesthesia with intraoperative real-time sensorimotor and language mappings using
      electrical stimulations all along the resection. Language tasks consisted of
      counting and picture naming (preceded by the reading of a short sentence).
      Stimulations of the left PMC induced transient speech disturbances in all
      patients, with disruption of both counting and reading/naming during stimulation
      of the ventral PMC--due to elicitation of an anarthria--while generating an
      anomia during stimulation of the dorsal PMC. Moreover, corresponding subcortical
      pathways generated the same language disorders as at the cortical level when
      stimulated. Eloquent structures were systematically preserved, allowing the
      avoidance of definitive postoperative deficit. These findings suggest first that
      the left dominant PMC seems to play a major role in language and second that this
      structure could have a well-ordered functional organization, namely with the
      ventral PMC, which might be involved in planification of articulation, and the
      dorsal PMC, which might be involved in the naming network.

PMID- 14683697
TI  - fMRI "deactivation" of the posterior cingulate during generalized spike and wave.
AB  - Using spike-triggered fMRI, we sought to document regional changes in blood
      oxygen level-dependent (BOLD) activity associated with spontaneous generalised
      spike and slow-wave discharges (S&W). Five adult patients were studied who had
      idiopathic generalised epilepsy (IGE) and frequent S&W. EEG was recorded inside a
      3T MRI, allowing acquisition of single, whole-brain fMRI images following S&W, as
      well as baseline images. Between 4 and 25 spike and wave complexes were captured
      in individuals. Four of the five individuals showed significant S&W-related BOLD
      signal reductions ("deactivation") in the posterior cingulate (P<0.001
      uncorrected). Significant changes were absent only in the individual with fewest
      spikes. Group analysis including all five subjects confirmed fMRI deactivation in
      the posterior cingulate. Some S&W-related BOLD signal increases were seen in the
      depths of the precentral sulci in individuals and on group analysis. No
      significant S&W-related changes in thalamic BOLD activity were observed. The
      posterior cingulate may have a role in the electroclinical phenomenon of S&W and
      "absence." Possibilities include a causative role, with reduced activity in the
      cingulate facilitating the onset of S&W, a secondary role, explaining the
      cognitive changes observed during prolonged S&W, or an epiphenomenon.

PMID- 14683698
TI  - An fMRI study of semantic processing in men with schizophrenia.
AB  - As a means toward understanding the neural bases of schizophrenic thought
      disturbance, we examined brain activation patterns in response to semantically
      and superficially encoded words in patients with schizophrenia. Nine male
      schizophrenic and 9 male control subjects were tested in a visual levels of
      processing (LOP) task first outside the magnet and then during the fMRI scanning
      procedures (using a different set of words). During the experiments visual words
      were presented under two conditions. Under the deep, semantic encoding condition,
      subjects made semantic judgments as to whether the words were abstract or
      concrete. Under the shallow, nonsemantic encoding condition, subjects made
      perceptual judgments of the font size (uppercase/lowercase) of the presented
      words. After performance of the behavioral task, a recognition test was used to
      assess the depth of processing effect, defined as better performance for
      semantically encoded words than for perceptually encoded words. For the scanned
      version only, the words for both conditions were repeated in order to assess
      repetition-priming effects. Reaction times were assessed in both testing
      scenarios. Both groups showed the expected depth of processing effect for
      recognition, and control subjects showed the expected increased activation of the
      left inferior prefrontal cortex (LIPC) under semantic encoding relative to
      perceptual encoding conditions as well as repetition priming for semantic
      conditions only. In contrast, schizophrenics showed similar patterns of fMRI
      activation regardless of condition. Most striking in relation to controls,
      patients showed decreased LIFC activation concurrent with increased left superior
      temporal gyrus activation for semantic encoding versus shallow encoding.
      Furthermore, schizophrenia subjects did not show the repetition priming effect,
      either behaviorally or as a decrease in LIPC activity. In patients with
      schizophrenia, LIFC underactivation and left superior temporal gyrus
      overactivation for semantically encoded words may reflect a disease-related
      disruption of a distributed frontal temporal network that is engaged in the
      representation and processing of meaning of words, text, and discourse and which
      may underlie schizophrenic thought disturbance.

PMID- 14683699
TI  - Isolating the retrieval of imagined pictures during episodic memory: activation
      of the left precuneus and left prefrontal cortex.
AB  - The posterior medial parietal cortex and the left prefrontal cortex have both
      been implicated in the recollection of past episodes. In order to clarify their
      functional significance, we performed this functional magnetic resonance imaging
      study, which employed event-related source memory and item recognition retrieval
      of words paired with corresponding imagined or viewed pictures. Our results
      suggest that episodic source memory is related to a functional network including
      the posterior precuneus and the left lateral prefrontal cortex. This network is
      activated during explicit retrieval of imagined pictures and results from the
      retrieval of item-context associations. This suggests that previously imagined
      pictures provide a context with which encoded words can be more strongly
      associated.

PMID- 14683700
TI  - Functional segregation of the temporal lobes into highly differentiated
      subsystems for auditory perception: an auditory rapid event-related fMRI-task.
AB  - With this study, we explored the blood oxygen level-dependent responses within
      the temporal lobe to short auditory stimuli of different classes. To address this
      issue, we performed an attentive listening event-related fMRI study, where
      subjects were required to concentrate during the presentation of different types
      of stimuli. Because the order of stimuli was randomized and not predictable for
      the subject, the observed differences between the stimuli types were interpreted
      as an automatic effect and were not affected by attention. We used three types of
      stimuli: tones, sounds of animals and instruments, and words. We found in all
      cases bilateral activations of the primary and secondary auditory cortex. The
      strength and lateralization depended on the type of stimulus. The tone trials led
      to the weakest and smallest activations. The perception of sounds increased the
      activated network bilaterally into the superior temporal sulcus mainly on the
      right and the perception of words led to the highest activation within the left
      superior temporal sulcus as well as in left inferior frontal gyrus. Within the
      left temporal sulcus, we were able to distinguish between different subsystems,
      showing an extending activation from posterior to anterior for speech and
      speechlike information. Whereas posterior parts were involved in analyzing the
      complex auditory structure of sounds and speech, the middle and anterior parts
      responded strongest only in the perception of speech. In summary, a functional
      segregation of the temporal lobes into several subsystems responsible for
      auditory processing was visible. A lateralization for verbal stimuli to the left
      and sounds to the right was already detectable when short stimuli were used.

PMID- 14683701
TI  - Contributions of stimulus valence and arousal to visual activation during
      emotional perception.
AB  - Neuroimaging experiments have revealed that the visual cortex is involved in the
      processing of affective stimuli: seeing emotional pictures leads to greater
      activation than seeing neutral ones. It is unclear, however, whether such
      differential activation is due to stimulus valence or whether the results are
      confounded by arousal level. In order to investigate the contributions of valence
      and arousal to visual activation, we created a new category of "interesting"
      stimuli designed to have high arousal, but neutral valence, and employed standard
      neutral, unpleasant, and pleasant picture categories. Arousal ratings for
      pleasant and neutral pictures were equivalent, as were valence ratings for
      interesting and neutral pictures. Differential activation for conditions matched
      for arousal (pleasant vs neutral) as well as matched for valence (interesting vs
      neutral) indicated that both stimulus valence and arousal contributed to visual
      activation.

PMID- 14683702
TI  - Functional connectivity analysis of the neural circuits of opiate craving: "more"
      rather than "different"?
AB  - We investigated the functional connectivity of brain regions activated during
      opiate craving. Previously we used recorded autobiographical scripts to induce
      opiate craving in 12 abstinent opiate-dependent subjects while they were
      undergoing positron emission tomography (PET) scanning using the regional
      cerebral blood flow (rCBF) tracer H2 15O. SPM99 was used to examine the
      connectivity patterns associated with the primary brain regions activated in
      response to drug-craving memories (anterior cingulate, AC) and correlated with
      opiate craving (orbitofrontal cortex, OFC). Two separate connectivity patterns
      were identified associated with the OFC and AC regions. The AC region was
      associated with activity in the left temporal region. The left OFC region
      activity correlated with activity in the right OFC, and left parietal and
      posterior insular regions. There was also a positive association with the
      hippocampus and brainstem. Both the AC and OFC regions showed a negative
      association with posterior visual areas. We suggest that the patterns of
      functional connectivity reflect the ability of drug-related stimuli to activate
      attentional and memory circuits to a greater degree than non-drug-related
      stimuli. This argues that neural circuits of dependence and craving are not
      specific "craving" or "addiction" brain regions but are "normal" circuits
      activated to a greater degree.

PMID- 14683703
TI  - Increase in peripheral benzodiazepine receptors and loss of glutamate NMDA
      receptors in a mouse model of closed head injury: a quantitative autoradiographic
      study.
AB  - Increases in peripheral type benzodiazepine receptors (PTBR) have been utilized
      for the detection of neuroinflammation and neurotoxicity in the brain. We have
      investigated the relationship between PTBR and NMDA receptor binding density in
      mice with closed head injury (CHI) using quantitative autoradiography. CHI was
      induced by a weight drop in nine mice, four of which received a single injection
      of the rat sarcoma (Ras) inhibitor famesyl thiosalicylate (FTS) 1 h after the
      insult. Sham controls received anesthesia but no contusion. The neurological
      status of the mice was evaluated at 1 h, and hence up to 7 days using a
      neurological severity score (NSS). Animals were killed 7 days after CHI and
      consecutive brain sections were incubated with [3H]PK11195, a PTBR antagonist, or
      [3H]MK801, an n-methyl-d-aspartate receptor (NMDAR) use-dependent antagonist. CHI
      produced large (two- to threefold), widespread increases in PK11195 binding in
      the traumatized hemisphere and a significant decrease (20%-40%) in NMDAR binding
      limited to regions at close proximity to the lesion. Histologically, these
      regions were characterized by glial proliferation and neuronal loss. Significant
      increases in PTBR binding, but no concomitant decrease in NMDAR, were identified
      in several regions remote from the lesion, including the contralateral
      ventrolateral striatum and the ipsilateral ventral thalamus. Drug treatment
      significantly improved the neurological deficits but had only a marginal effect
      on PTBR. These results support a complex role for glial activation and PTBR
      increases in the context of CHI.

PMID- 14683704
TI  - Systemic sulpiride modulates striatal blood flow: relationships to spatial
      working memory and planning.
AB  - The dopamine D2 receptor antagonist sulpiride can produce a range of cognitive
      deficits in normal volunteers, consistent with those seen in Parkinson's disease
      (PD). This, together with studies in experimental animals, implies sulpiride
      might be acting in the striatum. However, subtle changes in prefrontal cortex
      (PFC) activity are seen following L-Dopa withdrawal in PD during working memory
      tasks, suggesting that this may be a further site of action for dopamine D2
      receptor antagonists. We have investigated the effects of sulpiride within the
      PFC and striatum in normal male volunteers. In two separate experiments, using
      identical PET regional cerebral blood flow (rCBF) methods, a combined drug and
      psychological challenge was performed, utilising working memory and planning
      tasks, and oral sulpiride 400 mg and placebo. Data were analysed using SPM99.
      Sulpiride increased striatal rCBF bilaterally and the working memory and planning
      tasks activated discrete frontoparietal networks in keeping with previous
      studies. However, for the working memory tasks, no changes in performance or task
      induced rCBF were observed after sulpiride. For the planning task, improved
      performance was seen on sulpiride. Also, sulpiride attenuated striatal activity
      during planning (as assessed using a small volume correction, P<0.05 corrected),
      and this attenuation was related to performance changes. These findings suggest
      that (1) sulpiride produces clear increases in striatal rCBF, (2) in contrast to
      previous studies no effects of sulpiride on performance of the working memory
      tasks or the associated neural networks were observed, and (3) sulpiride may
      modulate performance of more complex cognitive tasks via alterations in striatal
      neural activity.

PMID- 14683706
TI  - ICA-based spatiotemporal approach for single-trial analysis of postmovement MEG
      beta synchronization.
AB  - The extraction of event-related oscillatory neuromagnetic activities from single
      trial measurement is challenging due to the non-phase-locked nature and
      variability from trial to trial. The present study presents a method based on
      independent component analysis (ICA) and the use of a template-based correlation
      approach to extract Rolandic beta rhythm from magnetoencephalographic (MEG)
      measurements of right finger lifting. A single trial recording was decomposed
      into a set of coupled temporal independent components and corresponding spatial
      maps using ICA and the reactive beta frequency band for each trial identified
      using a two-spectrum comparison between the postmovement interval and a reference
      period. Task-related components survived dual criteria of high correlation with
      both the temporal and the spatial templates with an acceptance rate of about 80%.
      Phase and amplitude information for noise-free MEG beta activities were preserved
      not only for optimal calculation of beta rebound (event-related synchronization)
      but also for profound penetration into subtle dynamics across trials. Given the
      high signal-to-noise ratio (SNR) of this method, various methods of source
      estimation were used on reconstructed single-trial data and the source loci
      coherently anchored in the vicinity of the primary motor area. This method
      promises the possibility of a window into the intricate brain dynamics of motor
      control mechanisms and the cortical pathophysiology of movement disorder on a
      trial-by-trial basis.

PMID- 14683705
TI  - Spatial normalization of diffusion tensor MRI using multiple channels.
AB  - Diffusion Tensor MRI (DT-MRI) can provide important in vivo information for the
      detection of brain abnormalities in diseases characterized by compromised neural
      connectivity. To quantify diffusion tensor abnormalities based on voxel-based
      statistical analysis, spatial normalization is required to minimize the
      anatomical variability between studied brain structures. In this article, we used
      a multiple input channel registration algorithm based on a demons algorithm and
      evaluated the spatial normalization of diffusion tensor image in terms of the
      input information used for registration. Registration was performed on 16 DT-MRI
      data sets using different combinations of the channels, including a channel of T2
      weighted intensity, a channel of the fractional anisotropy, a channel of the
      difference of the first and second eigenvalues, two channels of the fractional
      anisotropy and the trace of tensor, three channels of the eigenvalues of the
      tensor, and the six channel tensor components. To evaluate the registration of
      tensor data, we defined two similarity measures, i.e., the endpoint divergence
      and the mean square error, which we applied to the fiber bundles of target images
      and registered images at the same seed points in white matter segmentation. We
      also evaluated the tensor registration by examining the voxel-by-voxel alignment
      of tensors in a sample of 15 normalized DT-MRIs. In all evaluations, nonlinear
      warping using six independent tensor components as input channels showed the best
      performance in effectively normalizing the tract morphology and tensor
      orientation. We also present a nonlinear method for creating a group diffusion
      tensor atlas using the average tensor field and the average deformation field,
      which we believe is a better approach than a strict linear one for representing
      both tensor distribution and morphological distribution of the population.

PMID- 14683707
TI  - Personality influences limbic-cortical interactions during sad mood induction.
AB  - The current study examined limbic-cortical activation under transient emotional
      stress as a function of personality style. A ventral cingulate (Cg25)-centred
      limbic-cortical network was identified using positron emission tomography (PET)
      measures of regional cerebral blood flow (rCBF) during a sad mood challenge that
      demonstrated differences for individuals selected for specific patterns of
      Negative and Positive emotional traits, indexed by the NEO Personality Inventory
      Revised. Healthy subjects scoring both low on the dispositional Depression facet
      of Neuroticism (N3) and high on the Positive Emotions facet of Extraversion (E6)
      were compared to those scoring high on the Depression facet (N3) and low on
      Positive Emotions (E6), a combination of traits previously linked to normal
      variations in mood reactivity. Scan analyses were designed to further
      characterize known variations in Cg25 activity previously reported in studies of
      negative mood in both healthy subjects and depressed patients. A multivariate
      technique, partial least squares (PLS) demonstrated a divergent Cg25-mediated
      network that differentiated temperamentally negative (NAS) from temperamentally
      positive (PAS) subjects providing a potential neural link between these specific
      combinations of trait affective styles and vulnerability to depression.

PMID- 14683708
TI  - Assessment of microPET performance in analyzing the rat brain under different
      types of anesthesia: comparison between quantitative data obtained with microPET
      and ex vivo autoradiography.
AB  - MicroPET (positron emission tomography) has been implemented for use in
      experiments with small animals. However, the quantification and optimal
      conditions for scanning are not established yet. The aim of this study was to
      compare the results obtained by microPET with those by ex vivo autoradiography of
      rat brain slices, based on the 2-[18F]fluoro-2-deoxy-D-glucose (FDG) method, and
      to establish the optimal conditions for scanning. As an example, we examined
      glucose metabolism in the rat brain under 6 types of anesthesia and in the
      conscious state. The scanning conditions for the rat brain were (1) use of a 4-mm
      thick leaden jacket, (2) an energy window of 350-650 keV, and (3) a coincidence
      time window of 6 ns. Under these conditions, the quantitative ROI data from
      microPET showed a good correlation with the corresponding ROI data from FDG
      autoradiography in the animal study (r2=0.81). With our protocol, when anesthesia
      was started 40 min after the FDG injection, the glucose metabolism was almost the
      same as that in the conscious rat brain.

PMID- 14683709
TI  - MEG localization of rolandic spikes with respect to SI and SII cortices in benign
      rolandic epilepsy.
AB  - The purpose of this study was to study the relationship between interictal spike
      sources and somatosensory cortices in benign rolandic epilepsy of childhood
      (BREC) using a whole-scalp neuromagnetometer. We recorded spontaneous
      magnetoencephalography (MEG) and EEG signals and cortical somatosensory-evoked
      magnetic fields (SEFs) to electric stimulation of the median nerve in 9 children
      with BREC. Interictal rolandic discharges (RDs) and SEFs were analyzed by
      equivalent current dipole (ECD) modeling. Based on the orientation and locations
      of corresponding ECDs, we compared generators of RDs with primary (SI) and second
      somatosensory cortices (SII). Our results showed that RDs and SII responses had
      similar ECD orientation on the magnetic field maps. The ECDs of RDs were
      localized 15.3 +/- 1.9 and 12.2 +/- 2.8 mm anterior to SI and SII, respectively.
      The spatial distance on average from the location of RDs to SII (21.9 +/- 1.6 mm)
      cortex was significantly shorter than to SI cortex (29.7 +/- 1.7 mm) (P<0.01,
      Wilcoxon signed-rank test). In conclusion, the cortical generators for RDs in
      patients with BREC are localized in the precentral motor cortex, closer to hand
      SII than to SI cortex.

PMID- 14683710
TI  - Functional MRI with variable echo time acquisition.
AB  - A new functional MRI protocol that integrates variable echo time (TE) acquisition
      and a block-design paradigm is proposed and evaluated with finger-tapping motor
      task. Simulations and experimental data show that the blood oxygenation level
      dependent (BOLD) sensitivity achieved with this approach is comparable to that
      achieved using a conventional constant-TE protocol. The proposed variable-TE fMRI
      protocol provides valuable information that cannot be obtained with the constant
      TE protocol. First, a field inhomogeneity map can be derived from the multi-TE
      data and used to correct EPI geometric distortions. Second, changes of T2* values
      due to the BOLD effect can be quantified. Third, for brain regions with
      pronounced susceptibility field gradients, the reduced BOLD sensitivity may be
      compensated for when the acquired multi-TE data are processed appropriately
      (e.g., with weighted summation). Fourth, large venules and veins may possibly be
      identified (depending on the vessel orientation and volume fraction) by
      evaluating the phase values of the multi-TE data. Finally, magnetic field drift
      over time can be measured from dynamic field maps available with this protocol.

PMID- 14683711
TI  - Quantitative mapping of cerebral deoxyhemoglobin content using MR imaging.
AB  - In this study, we present a magnetic resonance imaging (MRI) method for
      quantifying cerebral deoxyhemoglobin content that is based on a measurement of
      the reversible contribution (R'2) of the transverse relaxation rate under the
      assumption of a quantitative relationship between R'2 and deoxyhemoglobin
      content. A numerical simulation was performed assuming a specific pulse sequence
      conventionally employed for R'2 measurement. The results showed a near linear
      relationship between R'2 and deoxyhemoglobin content in the physiological range
      of oxygen extraction for almost all sized vessels, although a large diffusion
      effect for capillary sized vessels compromised the relationship. Concerning the
      methodology for R'2 measurement, a theoretical analysis showed that
      multiexponential transverse signal decay of brain parenchyma may result in a
      considerable underestimation or overestimation of R'2, if a conventional method
      is employed for R'2 quantification. A modified method for correcting the effect
      of multiexponential signal decay was employed for R'2 measurement of the brain in
      normal volunteers. The results showed a high level of agreement between the R'2
      values measured in our study and those estimated from physiological parameters
      obtained using other modalities such as PET. In the context of BOLD contrast
      based functional MRI, the method proposed provides a quantitative mapping of
      baseline cerebral deoxyhemoglobin content, which is the essential physiological
      parameter for calibrating the stimulation-induced BOLD signal change and mapping
      neuronal activity in a quantitative manner by functional MRI.

PMID- 14683712
TI  - The neural correlates of perceiving one's own movements.
AB  - Feedforward mechanisms are important for movement control. They may also
      contribute to the identification of self-produced actions by attenuating the
      sensory consequences of self-produced movements. In our study, subjects opened
      and closed their hand slowly and continuously (0.5 Hz). This movement was filmed
      with an MRI compatible video camera and projected online onto a screen, viewed by
      the subject while BOLD contrast was measured with fMRI. The temporal delay
      between movement and feedback was parametrically varied (0-200 ms). In each
      trial, subjects judged whether there was a delay or not. There was a positive
      correlation between the extent of the temporal delay and activation in the right
      posterior superior temporal cortex (pSTS) and a negative correlation in the left
      putamen. A second analysis addressed the neural correlates of subjective
      judgement under conditions of uncertainty. This contrast showed a differential
      activation in the cerebellum. These results support the assumption of a forward
      model implying that predictions generated in motor areas attenuate sensory areas.
      They also suggest that efference copy mechanisms are not located within specific
      brain areas but are implemented as a specific form of interaction between
      perceptual and motor areas depending on the modalities and the type of actions
      involved. Further, conscious detection of small temporal deviations might be
      based on signals generated in the cerebellum which provide fine-grained temporal
      information. These results might be useful to refine theories about the role of
      forward mechanisms in the emergence of disorders of the self, such as in
      schizophrenia.

PMID- 14683713
TI  - Amygdala modulation of parahippocampal and frontal regions during emotionally
      influenced memory storage.
AB  - Considerable evidence from both animal and human subject research supports the
      hypothesis that the amygdala, when activated by emotional arousal, modulates
      memory storage processes in other brain regions. By this hypothesis, changes in
      the functional interactions of the amygdala with other brain regions during
      emotional conditions should underlie, at least in part, enhanced memory for
      emotional material. Here we examined the influence of the human amygdala on other
      brain regions under emotional and nonemotional learning conditions using
      structural equation modeling (SEqM). Eleven male subjects received two PET scans
      for regional cerebral glucose metabolism-one scan while viewing a series of
      emotionally provocative (negative) film clips and a second scan while viewing a
      series of more emotionally neutral film clips. Enhanced activity in the right
      amygdala was related to enhanced memory for the emotional films. To identify
      potential candidate voxels for SEqM, the functional connectivity of the maximally
      activated voxel within the right amygdala was investigated using partial least
      squares. A subset of regions identified by this analysis showing differences
      functional connectivity with the amygdala between the emotional versus neutral
      film conditions were then submitted to SEqM, which revealed significantly
      increased amygdala influences on the ipsilateral parahippocampal gyrus and
      ventrolateral prefrontal cortex during the emotional relative to the neutral film
      viewing condition. These findings support the view that increased influences from
      the amygdala, presumably reflecting its memory-modulation function, occur during
      emotionally arousing learning situations.

PMID- 14683714
TI  - Development and evaluation of an automated atlas-based image analysis method for
      microPET studies of the rat brain.
AB  - An automated method for placement of 3D rat brain atlas-derived volumes of
      interest (VOIs) onto PET studies has been designed and evaluated. VOIs
      representing major structures of the rat brain were defined on a set of digitized
      cryosectioned images of the rat brain. For VOI placement, each PET study was
      registered with a synthetic PET target constructed from the VOI template.
      Registration was accomplished with an automated algorithm that maximized the
      mutual information content of the image volumes. The accuracy and precision of
      this method for VOI placement was determined using datasets from PET studies of
      the striatal dopamine and hippocampal serotonin systems. Each evaluated PET study
      could be registered to at least one synthetic PET target without obvious failure.
      Registration was critically dependent upon the initial position of the PET study
      relative to the synthetic PET target, but not dependent on the amount of
      synthetic PET target smoothing. An evaluation algorithm showed that resultant
      radioactivity concentration measurements of selected brain structures had
      errors=2% due to misalignment with the corresponding VOI. Further, radioligand
      binding values calculated from these measurements were found to be more precise
      than those calculated from measurements obtained with manually drawn regions of
      interest (ROIs). Overall, evaluation results demonstrated that this atlas-derived
      VOI method can be used to obtain unbiased measurements of radioactivity
      concentration from PET studies. Its automated features, and applicability to
      different radioligands and brain regions, will facilitate quantitative rat brain
      PET assessment procedures.

PMID- 14683715
TI  - One brain, two selves.
AB  - Having a sense of self is an explicit and high-level functional specialization of
      the human brain. The anatomical localization of self-awareness and the brain
      mechanisms involved in consciousness were investigated by functional neuroimaging
      different emotional mental states of core consciousness in patients with Multiple
      Personality Disorder (i.e., Dissociative Identity Disorder (DID)). We demonstrate
      specific changes in localized brain activity consistent with their ability to
      generate at least two distinct mental states of self-awareness, each with its own
      access to autobiographical trauma-related memory. Our findings reveal the
      existence of different regional cerebral blood flow patterns for different senses
      of self. We present evidence for the medial prefrontal cortex (MPFC) and the
      posterior associative cortices to have an integral role in conscious experience.

PMID- 14683716
TI  - Postnatal changes in intrinsic optical responses to peripheral nerve stimulation
      in the in vivo rat spinal cord.
AB  - We previously applied an intrinsic optical imaging technique to the in vivo rat
      spinal cord, and showed its feasibility for analyzing neural functions. Three- to
      7-week-old postnatal and adult (>10-week-old) rats were anesthetized and
      laminectomy was performed between C5 and Th1 to expose the dorsal surface of the
      cervical spinal cord. Optical reflectance changes in response to simultaneous
      stimulation of the median and ulnar nerves were recorded from the spinal cord at
      a depth corresponding to the dorsal horn (substantia gelatinosa), using a
      differential video acquisition system. The shape and extent of the area of the
      evoked optical signals varied during postnatal development. In 3- to 4-week-old
      rats, the response area was small and ellipsoidal, and constrictions between
      spinal segments were not clear. As postnatal ages proceeded, the area expanded in
      a rostrocaudal direction, and the constrictions became clear. In adult rats, the
      response area exhibited a segmental pattern. At all ages, the optical responses
      showed trial-to-trial variations. A semiquantitative analysis of the variations
      in one spinal segment showed that the variations in a mediolateral direction
      appeared to decrease slightly with development, although statistical differences
      were insignificant between ages. The dynamical changes in optical response
      patterns were discussed in relation to postnatal maturation of neural functions
      in the spinal cord.

PMID- 14683717
TI  - Parametric manipulation of conflict and response competition using rapid mixed
      trial event-related fMRI.
AB  - In the current study we examined the influence of preceding context on
      attentional conflict and response competition using a flanker paradigm. Nine
      healthy right-handed adults participated in a rapid mixed trial event-related
      functional magnetic resonance imaging (fMRI) study, in which increasing numbers
      of either compatible or incompatible trials preceded an incompatible trial.
      Behaviorally, reaction times on incompatible trials increased as a function of
      the number of preceding compatible trials. Several brain regions showed monotonic
      changes to the preceding context manipulation. The most common pattern was
      observed in anterior cingulate, dorsolateral prefrontal, and superior parietal
      regions. These areas showed an increase in activity for incompatible trials as
      the number of preceding compatible trials increased and a decrease in activity
      for incompatible trials as the number of preceding incompatible trials increased.
      Post hoc analysis showed that while the MR signal in the anterior cingulate and
      dorsolateral prefrontal regions peaked before the superior parietal region, the
      dorsolateral prefrontal MR signal peaked early and remained at this level. These
      findings are consistent with the conflict monitoring theory that postulates that
      the anterior cingulate cortex detects or monitors conflict, while PFC is involved
      in control adjustments that may then lead to modulation of superior parietal
      cortex in top-down biasing of attention.

PMID- 14683718
TI  - Musical structure is processed in "language" areas of the brain: a possible role
      for Brodmann Area 47 in temporal coherence.
AB  - The neuroanatomical correlates of musical structure were investigated using
      functional magnetic neuroimaging (fMRI) and a unique stimulus manipulation
      involving scrambled music. The experiment compared brain responses while
      participants listened to classical music and scrambled versions of that same
      music. Specifically, the scrambled versions disrupted musical structure while
      holding low-level musical attributes constant, including the psychoacoustic
      features of the music such as pitch, loudness, and timbre. Comparing music to its
      scrambled counterpart, we found focal activation in the pars orbitalis region
      (Brodmann Area 47) of the left inferior frontal cortex, a region that has been
      previously closely associated with the processing of linguistic structure in
      spoken and signed language, and its right hemisphere homologue. We speculate that
      this particular region of inferior frontal cortex may be more generally
      responsible for processing fine-structured stimuli that evolve over time, not
      merely those that are linguistic.

PMID- 14683719
TI  - A rapid algorithm for robust and automatic extraction of the midsagittal plane of
      the human cerebrum from neuroimages based on local symmetry and outlier removal.
AB  - A rapid algorithm for robust, accurate, and automatic extraction of the
      midsagittal plane (MSP) of the human cerebrum from normal and pathological
      neuroimages is proposed. The MSP is defined as a plane formed from the
      interhemispheric fissure line segments having the dominant orientation. The
      algorithm extracts the MSP in four steps: (1) determine suitable axial slices for
      processing, (2) localize the fissure line segments on them, (3) select inliers
      from the extracted fissure line segments through histogram-based outlier removal,
      and (4) calculate the equation of the MSP from the selected inliers. The fissure
      line segments are localized by minimizing the local symmetry index characterizing
      anatomical properties of images in the vicinity of the interhemispheric fissure.
      A two-stage angular and distance outlier removal is introduced to handle
      abnormalities. The algorithm has been validated quantitatively with 125
      structural MRI and CT cases from 10 centers on three continents by studying its
      accuracy; tolerance to rotation, noise, asymmetry, and bias field; sensitivity to
      parameters; and performance. A statistical relationship between algorithm
      accuracy and the data's adherence to planarity is also determined. The algorithm
      extracts the MSP below 6 s on Pentium 4 (2.4 GHz) with the average angular and
      distance errors of (0.40 degrees; 0.63 mm) for normal and (0.59 degrees; 0.73 mm)
      for pathological cases. The robustness to noise, asymmetry, rotation, and bias
      field is achieved by extracting the MSP based on the dominant orientation and
      local symmetry index. A low computational cost results from applying simple
      operations capturing intrinsic anatomic features, constraining the searching
      space to the local vicinity of the interhemispheric fissure, and formulating a
      noniterative algorithm with a coarse and fine fixed-step searching. In comparison
      to the existing methods, our algorithm is much faster, performs accurately and
      robustly for a wide range of diversified data, and is fully automatic and
      thoroughly validated, which make it suitable for clinical applications.

PMID- 14683720
TI  - Correlation between cerebral reorganization and motor recovery after subcortical
      infarcts.
AB  - Our objective was to investigate correlations between clinical motor scores and
      cerebral sensorimotor activation to demonstrate that this reorganization is the
      neural substratum of motor recovery. Correlation analyses identified
      reorganization processes shared by all patients. Nine patients with first-time
      corticospinal tract lacuna were clinically evaluated using the NIH stroke scale,
      the motricity index, and the Barthel index. Patients were strictly selected for
      pure motor deficits. They underwent a first fMRI session (E1) 11 days after
      stroke, and then a second (E2) 4 weeks later. The task used was a calibrated
      repetitive passive flexion/extension of the paretic wrist. The control task was
      rest. Six healthy subjects followed the same protocol. Patients were also
      clinically evaluated 4 and 12 months after stroke. All patients improved
      significantly between E1 and E2. For E1 and E2, the ipsilesional primary
      sensorimotor and premotor cortex, supplementary motor area (SMA), and bilateral
      Broadmann area (BA) 40 were activated. Activation intensity was greater at the
      second examination except in the ipsilesional superior BA 40. Magnitude of
      activation was lower than that of controls except for well-recovered patients. E1
      clinical hand motor score and E1 cerebral activation correlated in the SMA proper
      and inferior ipsilesional BA 40. Thus, we demonstrated early functionality of the
      sensorimotor system. The whole sensorimotor network activation correlated with
      motor status at E2, indicating a recovery of its function when activated.
      Moreover, the activation pattern in the acute phase (E1) had a predictive value:
      early recruitment and high activation of the SMA and inferior BA 40 were
      correlated with a faster or better motor recovery. On the contrary, activation of
      the contralesional hemisphere (prefrontal cortex and BA 39-40) and of the
      posterior cingulate/precuneus (BA 7-31) predicted a slower recovery.

PMID- 14683721
TI  - Multilingualism: an fMRI study.
AB  - To investigate the hypothesis that in multilingual speakers different languages
      are represented in distinct brain regions, 12 multilingual right-handed men
      performed a word fluency task, a picture naming task, a comprehension reading
      task, and their respective control tasks in three languages (Dutch, French, and
      English) while whole-head functional magnetic resonance imaging (fMRI) was
      applied. In general, all language tasks revealed predominantly overlapping
      regions of activation for the different languages. Cerebral activation during use
      of the foreign languages showed a tendency toward a more extensive recruitment of
      the areas activated in the native language and the activation of a greater number
      of regions. Word generation in the foreign languages elicited additional
      bilateral inferior frontal activation, including Broca's area and left middle
      temporal gyrus activation; in the native language, additional postcentral
      activation was found. Picture naming in the foreign languages recruited
      additional inferior-lateral and medial frontal regions predominantly on the left,
      and more posterior right hemispheric activation in the mother tongue. During
      comprehension reading there was more activation in medial posterior regions in
      the native language. Our results suggest that the performance of language tasks
      in different languages engages largely the same cerebral areas but that the
      brain, to perform at a comparable proficiency level, engages more neural
      substrates for later acquired languages. Our findings do not support the view
      that languages learned later in life entail more right hemispheric involvement.
      Finally, a consequent effect of language exposure was found for reading, where
      increased familiarity engages more occipital activation whereas decreased
      familiarity appears to be associated with increased left hemispheric inferior
      frontal activation.

PMID- 14683722
TI  - Group analysis in functional neuroimaging: selecting subjects using similarity
      measures.
AB  - Standard group analyses of fMRI data rely on spatial and temporal averaging of
      individuals. This averaging operation is only sensible when the mean is a good
      representation of the group. This is not the case if subjects are not
      homogeneous, and it is therefore a major concern in fMRI studies to assess this
      group homogeneity. We present a method that provides relevant distances or
      similarity measures between temporal series of brain functional images belonging
      to different subjects. The method allows a multivariate comparison between data
      sets of several subjects in the time or in the space domain. These analyses
      assess the global intersubject variability before averaging subjects and drawing
      conclusions across subjects, at the population level. We adapt the RV coefficient
      to measure meaningful spatial or temporal similarities and use multidimensional
      scaling to give a visual representation of each subject's position with respect
      to other subjects in the group. We also provide a measure for detecting subjects
      that may be outliers. Results show that the method is a powerful tool to detect
      subjects with specific temporal or spatial patterns, and that, despite the
      apparent loss of information, restricting the analysis to a homogeneous subgroup
      of subjects does not reduce the statistical sensitivity of standard group fMRI
      analyses.

PMID- 14683723
TI  - Real-time independent component analysis of fMRI time-series.
AB  - Real-time functional magnetic resonance imaging (fMRI) enables one to monitor a
      subject's brain activity during an ongoing session. The availability of online
      information about brain activity is essential for developing and refining
      interactive fMRI paradigms in research and clinical trials and for neurofeedback
      applications. Data analysis for real-time fMRI has traditionally been based on
      hypothesis-driven processing methods. Off-line data analysis, conversely, may be
      usefully complemented by data-driven approaches, such as independent component
      analysis (ICA), which can identify brain activity without a priori temporal
      assumptions on brain activity. However, ICA is commonly considered a time
      consuming procedure and thus unsuitable to process the high flux of fMRI data
      while they are acquired. Here, by specific choices regarding the implementation,
      we exported the ICA framework and implemented it into real-time fMRI data
      analysis. We show that, reducing the ICA input to a few points within a time
      series in a sliding-window approach, computational times become compatible with
      real-time settings. Our technique produced accurate dynamic readouts of brain
      activity as well as a precise spatiotemporal history of quasistationary patterns
      in the form of cumulative activation maps and time courses. Results from real and
      simulated motor activation data show comparable performances for the proposed ICA
      implementation and standard linear regression analysis applied either in a
      sliding-window or in a cumulative mode. Furthermore, we demonstrate the
      possibility of monitoring transient or unexpected neural activities and suggest
      that real-time ICA may provide the fMRI researcher with a better understanding
      and control of subjects' behaviors and performances.

PMID- 14683724
TI  - Preserved functional competence of perilesional areas in drug-resistant epilepsy
      with lesion in supplementary motor cortex: fMRI and neuropsychological
      observations.
AB  - We report a presurgical fMRI study and a longitudinal behavioral and structural
      MRI study in a 26-year-old right-handed woman with drug-resistant epilepsy of the
      supplementary motor region with cytoarchitectural dysplasia and minimal cortico
      subcortical gliotic damage. fMRI scans were acquired during a silent phonemic
      verbal fluency task (VF), an automatic counting task (CT), and a finger-tapping
      motor task (MT). These were all compared with rest. Presurgical
      neuropsychological assessment was substantially normal with only a minor deficit
      in the domain of visuo-constructive and complex motor-planning skills.
      Noticeably, performance on phonemic verbal fluency was normal. Presurgical fMRI
      results revealed a normal specialization of left SMA and pre-SMA, including a
      fine-grained somatotopy for mouth and hand representations despite epilepsy.
      Immediately after surgical removal of the epileptogenic zone (the posterior third
      of the superior and middle frontal gyri including pre-SMA and part of SMA, and
      part of the anterior cingulate region--all of which were active presurgically at
      the fMRI tests), the patient suffered from transcortical motor aphasia
      temporarily. One year after surgery, she still showed impaired performance in the
      verbal fluency tasks while naming and comprehension were recovered. The patient
      was now free from seizures. This fMRI study supports the case that repeated
      seizures per se may not be sufficient to alter the distribution of neural
      representations of cognitive function. Selective behavioral impairment after
      surgical removal of brain areas that were activated during presurgical fMRI
      permits us to establish a causal link between these activations and task
      performance. This link could not have been made on the basis of activation
      patterns or lesion data taken on their own. These findings support the case that
      some epileptic patients may represent a unique opportunity for cognitive
      neuroscience studies.

PMID- 14683725
TI  - Magnetoencephalographic--features related to mild cognitive impairment.
AB  - We recorded changes of brain activity from 10 MCI patients and 10 controls
      related to shallow (nonsemantic) and deep (semantic) word encoding using a whole
      head MEG. During the following recognition tasks, all participants had to
      recognize the previously encoded words, which were presented again together with
      new words. In both groups recognition performance significantly varied as a
      function of depth of processing. No significant differences were found between
      the groups. Reaction times related to correctly classified new words (correct
      rejections) and incorrectly classified repetitions (misses) of MCI patients
      showed a strong tendency toward prolongation compared to controls, although no
      statistically significant differences occurred. Strikingly, in patients the
      neurophysiological data associated with nonsemantic and semantic word encoding
      differed significantly between 250 and 450 ms after stimulus onset mainly over
      left frontal and left temporal sensors. They showed higher electrophysiological
      activation during shallow encoding as compared to deep encoding. No such
      significant differences were found in controls. The present results might reflect
      a dysfunction with respect to shallow encoding of visually presented verbal
      information. It is interpreted that additional neural activation is needed to
      compensate for neurodegeneration. This finding is suggested to be an additional
      tool for MCI diagnosis.

PMID- 14683726
TI  - Processing abstract auditory features in the human auditory cortex.
AB  - Using electric and magnetic brain responses we tested whether violations of an
      abstract auditory regularity are processed in auditory cortex and whether
      abstract auditory regularities are retained for at least 10 s. The mismatch
      negativity (MMN) event-related potential and its magnetic counterpart (MMNm) were
      recorded to infrequent tone pairs of descending pitch (the second tone having a
      lower frequency than the first one) embedded in a sequence of tone pairs of
      ascending pitch, whereas the absolute frequency of both ascending and descending
      tone pairs varied on seven levels. Results showed that the dominant generators of
      the electromagnetic activity elicited by violations of the pitch-ascension rule
      lie within auditory cortex. We also found that the memory representation of pitch
      ascension is retained for at least 10 s. When short trains of ascending-pitched
      tone pairs were followed by a silent period of 8-12 s, descending-pitched probe
      tone pairs elicited the MMN component when a single reminding pair with ascending
      pitch was presented before the probe. The reactivating effect of the reminder was
      similar to what has been previously shown for concrete auditory regularities,
      such as the constancy of tone pitch. The present results support the view that
      auditory cortical functions can process sensory and categorical information in a
      similar manner.

PMID- 14683727
TI  - Ipsilateral motor cortex activation on functional magnetic resonance imaging
      during unilateral hand movements is related to interhemispheric interactions.
AB  - Distal, unilateral hand movements can be associated with activation of both
      sensorimotor cortices on functional MRI. The neurophysiological significance of
      the ipsilateral activation remains unclear. We examined 10 healthy right-handed
      subjects with and without activation of the ipsilateral sensorimotor area during
      unilateral index-finger movements, to examine ipsilateral, uncrossed-descending
      pathways and interhemispheric interaction between bilateral motor areas, using
      transcranial magnetic stimulation (TMS). No subject showed ipsilateral activation
      during right hand movement. Five subjects showed ipsilateral sensorimotor
      cortical activation during left hand movement (IpsiLM1). In these subjects,
      paired-pulse TMS revealed a significant interhemispheric inhibition of the left
      motor cortex by the right hemisphere that was not present in the 5 subjects
      without IpsiLM1. Neither ipsilateral MEPs nor ipsilateral silent periods were
      evoked by TMS in any subjects. Our observation suggests that IpsiLM1 is not
      associated with the presence of ipsilateral uncrossed-descending projections.
      Instead, IpsiLM1 may reveal an enhanced interhemispheric inhibition from the
      right hemisphere upon the left to suppress superfluous, excessive activation.

PMID- 14683728
TI  - Spatial working memory deficits in obsessive compulsive disorder are associated
      with excessive engagement of the medial frontal cortex.
AB  - Recent studies have shown that obsessive compulsive disorder (OCD) is associated
      with a specific deficit in spatial working memory, especially when task
      difficulty (i.e., working memory load) is high. It is not clear whether this
      deficit is associated with dysfunction of the brain system that subserves spatial
      working memory, or whether it is associated with a more generalized effect on
      executive functions. In contrast to studies in healthy volunteers and
      schizophrenia, spatial working memory in OCD has not been investigated before
      using functional neuroimaging techniques. We conducted a functional MRI study in
      11 treatment-free female patients with OCD and 11 for sex-, age-, education-, and
      handedness pairwise-matched healthy controls in order to assess performance on a
      parametric spatial n-back task as well as the underlying neuronal substrate and
      its dynamics. Patients with OCD performed poorly at the highest level of task
      difficulty and engaged the same set of brain regions as the matched healthy
      controls. In this set, the effect of difficulty on magnitude of brain activity
      was the same in patients and in controls except for a region covering the
      anterior cingulate cortex. In this region activity was significantly elevated in
      patients with OCD at all levels of the parametric task. These findings do not
      provide evidence for a deficit of the spatial working memory system proper, but
      suggest that the abnormal performance pattern may be secondary to another aspect
      of executive dysfunctioning in OCD.

PMID- 14683729
TI  - Quantitative MR image analysis in subjects with defects in the PAX6 gene.
AB  - Cerebral development is governed by genetic and environmental factors. Animal
      models provide much of our knowledge about genetic influences in the brain but it
      is not clear how similar or relevant these are to the human brain. The
      investigation of human subjects with mutations in genes known to be expressed in
      the developing brain is an alternative approach to improving our understanding of
      the role of genetic factors in brain development. We investigated 24 subjects
      with known mutations in the PAX6 gene (including representatives of all the known
      mutations of the gene) which are associated with characteristic ocular
      abnormalities in humans and animals. We have quantified MRI data using several
      techniques to assess qualities of cerebral structure which are difficult to
      interpret visually. Abnormalities were identified using voxel-based morphometry,
      statistical morphometrics, and measurement of corpus callosum cross-sectional
      area when comparing data from subjects with PAX6 abnormality and 72 age-and sex
      matched control subjects. These abnormalities include grey matter changes in the
      cerebellum and occipital poles and white matter loss in the corpus callosum,
      alteration of sulcal orientation in the occipital lobe, and alteration to overall
      neuronal connectivity. These abnormalities complement and exceed the changes seen
      in the mouse models, and those seen on visual inspection alone of the human MRI
      data. Structural differences were also identified between the two largest
      genotype mutation subgroups.

PMID- 14683730
TI  - The influence of brain tumor treatment on pathological delta activity in MEG.
AB  - The goal of the MEG study was to investigate the influence of tumor treatment on
      pathological delta activity (1-4 Hz). The treatment consisted of neurosurgery,
      and in some of the patients, additional radiotherapy. MEG and MR recordings were
      made both before and after the treatment in 17 patients. The signal power in the
      delta frequency band was determined for each recording. The malignant tumors were
      associated with large tumor volumes. Furthermore, both malignant tumors and tumor
      volume were associated with high signal powers in the delta band, indicating a
      correlation of delta power with the severity of the lesions. In all patients with
      high grade tumors, the delta power was lower after the treatment. The sources
      underlying the delta signals were estimated with an automatic single dipole
      analysis method. Estimated sources were projected onto MR scans. Preoperatively
      14 clusters of equivalent sources describing focal activity were found in 12 out
      of 17 patients. Thirteen of these clusters were located near the tumor, and one
      cluster near an edema border. The locations near tumors are plausible and suggest
      that in general the source estimation was reliable. After the operation, 13 such
      clusters were found in 12 patients. Eleven clusters were located near the lesion
      border and one cluster near the edema border. Furthermore a cluster contralateral
      to the lesion in the other hemisphere indicated that brain lesions can affect the
      functioning of more distant brain areas than just the peritumoral brain tissue.
      Of the 12 patients who had preoperatively peritumoral clusters, 11 patients had
      postoperatively perilesional sources. In these cases the shift in source
      locations was in general considerably smaller than the dimension of the
      preoperative tumors. This finding indicates that similar areas generate the pre-
      and postoperative delta activity. Furthermore, focal delta sources were found in
      a case without tumor recurrence, and also in cases that most tumor tissue was
      removed. These findings suggest that the pathology underlying the slow waves is
      not the presence of the tumor bulk but the structural damage done by the tumors
      on the surrounding white/gray matter.

PMID- 14683731
TI  - The use of anatomical constraints with MEG beamformers.
AB  - Synthetic Aperture Magnetometry (SAM) is a beamformer approach for the
      localisation of neuronal activity from EEG/MEG data. SAM estimates the optimum
      orientation of each source in a predefined source space by a nonlinear search for
      the orientation that maximises the beamformer output. However, MEG is most
      sensitive to cortical sources and these sources are generally oriented
      perpendicular to the surface. The reconstructed neuronal activity can therefore
      reasonably be constrained to the cortical surface, orientated perpendicular to
      it, therefore removing the search for the optimum orientation for the computation
      of the beamformer weights. This paper sets out to compare the performance of a
      constrained and unconstrained beamformer (SAM), with respect to the localisation
      accuracy of the source reconstructions and the spatial resolution. Fifty sources
      were randomly placed on a cortical surface estimated from an MRI, and we
      simulated data over a range of different signal-to-noise ratios (SNRs) for each
      source. These datasets were analysed using both an unconstrained beamformer (SAM)
      and a constrained beamformer (with the sources orientated perpendicular to the
      cortical surface). The influence of errors in the estimation of the surface
      location and surface normals on the performance of the constrained beamformer,
      representing MEG/MRI coregistration and segmentation errors, were also examined.
      The spatial resolution of the beamformer improves, typically by a factor of four
      by applying anatomical constraints, and the localisation accuracy improves
      marginally. However, the advantage in spatial resolution disappears when errors
      are introduced into the orientation and location constraints, and, moreover, the
      localisation accuracy of the inaccurately constrained beamformer degrades
      rapidly. We conclude that the use of anatomical constraints is only advantageous
      if the MEG/MRI coregistration error is smaller than 2 mm and the error in the
      estimation of the cortical surface orientation is smaller than 10 degrees.

PMID- 14683732
TI  - Reciprocal neural response within lateral and ventral medial prefrontal cortex
      during hot and cold reasoning.
AB  - Logic is widely considered the basis of rationality. Logical choices, however,
      are often influenced by emotional responses, sometimes to our detriment,
      sometimes to our advantage. To understand the neural basis of emotionally neutral
      ("cold") and emotionally salient ("hot") reasoning we studied 19 volunteers using
      event-related fMRI, as they made logical judgments about arguments that varied in
      emotional saliency. Despite identical logical form and content categories across
      "hot" and "cold" reasoning conditions, lateral and ventral medial prefrontal
      cortex showed reciprocal response patterns as a function of emotional saliency of
      content. "Cold" reasoning trials resulted in enhanced activity in lateral/dorsal
      lateral prefrontal cortex (L/DLPFC) and suppression of activity in ventral medial
      prefrontal cortex (VMPFC). By contrast, "hot" reasoning trials resulted in
      enhanced activation in VMPFC and suppression of activation in L/DLPFC. This
      reciprocal engagement of L/DLPFC and VMPFC provides evidence for a dynamic neural
      system for reasoning, the configuration of which is strongly influenced by
      emotional saliency.

PMID- 14683733
TI  - Task switching: a high-density electrical mapping study.
AB  - Flexibly switching between tasks is one of the paradigmatic functions of so
      called "executive control" processes. Neuroimaging studies have implicated both
      prefrontal and parietal cortical regions in the processing necessary to
      effectively switch task. Beyond their general involvement in this critical
      function, however, little is known about the dynamics of processing across
      frontal and parietal regions. For instance, it remains to be determined to what
      extent these areas play a role in preparing to switch task before arrival of the
      stimulus to be acted upon and to what extent they play a role in any switching
      processes that occur after the stimulus is presented. Here, we used the excellent
      temporal resolution afforded by high-density mapping of brain potentials to
      explore the time course of the processes underlying (1) the performance of and
      (2) the preparation for a switch of task. We detail the contributions of both
      frontal and parietal processes to these two aspects of the task-switching
      process. Our data revealed a complex pattern of effects. Most striking was a
      period of sustained activity over bilateral parietal regions preceding the switch
      trial. Over frontal regions, activity actually decreased during this same period.
      Strongest sustained frontal activity was in fact seen for trials on which no
      switch was required. Further, we find that the first differential activity
      associated with switching task was over posterior parietal areas (220 ms),
      whereas over frontal scalp, the first differential activity is found more than
      200 ms later. These and other effects are interpreted in terms of a "competition"
      model in which preparing to switch task is understood as the beginning of a
      competition between the potentially relevant tasks that is resolved during the
      switch trial. Our findings are difficult to account for with models that posit a
      strong role for frontal cortical regions in "reconfiguring" the system during
      switches of task.

PMID- 14683734
TI  - Validating cluster size inference: random field and permutation methods.
AB  - Cluster size tests used in analyses of brain images can have more sensitivity
      compared to intensity based tests. The random field (RF) theory has been widely
      used in implementation of such tests, however the behavior of such tests is not
      well understood, especially when the RF assumptions are in doubt. In this paper,
      we carried out a simulation study of cluster size tests under varying smoothness,
      thresholds, and degrees of freedom, comparing RF performance to that of the
      permutation test, which is known to be exact. For Gaussian images, we find that
      the RF methods are generally conservative, especially for low smoothness and low
      threshold. For t images, the RF tests are found to be conservative at lower
      thresholds and do not perform well unless the threshold is high and images are
      sufficiently smooth. The permutation test performs well for any settings though
      the discreteness in cluster size must be accounted for. We make specific
      recommendations on when permutation tests are to be preferred to RF tests.

PMID- 14683735
TI  - HOPE brings hope for the use of the ankle-brachial index as cardiovascular risk
      marker.

PMID- 14683736
TI  - Coronary artery disease and depression.
AB  - Coronary artery disease (CAD) as well as depression are both highly prevalent
      diseases. Both cause a significant decrease in quality of life for the patient
      and impose a significant economic burden on society. There are several factors
      that seem to link depression with the development of CAD and with a worse outcome
      in patients with established CAD: worse adherence to prescribed medication and
      life style modifications in depressive patients, as well as higher rates in
      abnormal platelet function, endothelial dysfunction and lowered heart rate
      variability. The evidence is growing that depression per se is an independent
      risk factor for cardiac events in a patient population without known CAD and also
      in patients with established diagnosis of CAD, particularly after myocardial
      infarction. Treatment of depression has been shown to improve patients' quality
      of life. However, it did not improve cardiovascular prognosis in depressed
      patients even though there is open discussion about the trend to better outcome
      in treated patients. Large scale clinical trials are needed to answer this
      question. Selective serotonin reuptake inhibitors seem to be preferable to
      tricyclic antidepressants for treatment of depressive patients with comorbid CAD
      because of their good tolerability and absence of significant cardiovascular side
      effects. Hypericum perforatum (St. John's wort), an increasingly used herbal
      antidepressant drug should be used with caution due to severe and possibly
      dangerous interaction with cardioactive drugs.

PMID- 14683737
TI  - Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients:
      meta-analysis of seven long-term studies.
AB  - AIMS: To assess if treatment with the alpha-glucosidase inhibitor acarbose can
      reduce cardiovascular events in type 2 diabetic patients. METHODS AND RESULTS:
      This meta-analysis included seven randomized, double-blind, placebo-controlled
      acarbose studies with a minimum treatment duration of 52 weeks. Type 2 diabetic
      patients valid for safety were randomized to either acarbose (n=1248) or placebo
      (n=932). The primary outcome measure was the time to develop a cardiovascular
      event. Primary analysis was conducted using Cox regression analysis. The effect
      of acarbose on metabolic parameters was also investigated. Acarbose therapy
      showed favourable trends towards risk reduction for all selected cardiovascular
      event categories. The treatment significantly reduced the risk for "myocardial
      infarction" (hazards ratio=0.36 [95% Cl 0.16-0.80], P=0.0120) and "any
      cardiovascular event" (0.65 [95% Cl 0.48-0.88], P=0.0061). Glycaemic control,
      triglyceride levels, body weight and systolic blood pressure also improved
      significantly during acarbose treatment. CONCLUSION: Intervention with acarbose
      can prevent myocardial infarction and cardiovascular disease in type 2 diabetic
      patients while most of them are already on intensive concomitant cardiovascular
      medication.

PMID- 14683738
TI  - Impact of ramipril in patients with evidence of clinical or subclinical
      peripheral arterial disease.
AB  - AIMS: The aim of this study was to assess the prognostic importance of peripheral
      arterial disease (PAD) as evaluated by ankle blood pressure index (ABI), and the
      impact of ramipril on the prevention of major cardiovascular events in PAD
      patients included in the Heart Outcomes Prevention Evaluation (HOPE) study.
      METHODS AND RESULTS: Patients were randomized to treatment with ramipril or
      placebo and followed for 4.5 years. Ankle brachial blood pressure index was
      measured, mainly by digital palpation of the foot pulse, at baseline in 8986
      patients. The ABI was subnormal (< or =0.9) in 3099 patients and normal in 5887
      patients. A low ABI was a strong predictor of morbidity and mortality during the
      follow-up even in patients with no clinical symptoms of PAD (n=6769). This was so
      for the primary outcome of the study; ABI>0.9:13.1%, 0.6-0.9: 18.2% and <0.6:
      18.0% (P<0.0001) and for mortality from all causes: in those with a normal ABI it
      was 8.5%, in those with ABI >0.6-0.9, 12.4% and 14.2% in those with an ABI lower
      than 0.6 (P<0.0001). Ramipril reduced the risk of clinical outcomes in those with
      a clinical history of PAD as well as in the patients with subclinical PAD.
      CONCLUSIONS: The ABI even if measured simply by palpation of the foot arteries is
      a strong predictor for future cardiovascular events and for all-cause mortality.
      Ramipril prevented major cardiovascular events in patients with clinical as well
      as subclinical PAD.

PMID- 14683739
TI  - Flu vaccination in acute coronary syndromes and planned percutaneous coronary
      interventions (FLUVACS) Study.
AB  - AIMS: We have previously reported a significant benefit of vaccination against
      flu on the incidence of a single and composite end-point of death, myocardial
      infarction or recurrent ischaemia in patients with myocardial necrosis and
      planned percutaneous coronary interventions. To determine whether the observed
      benefits of vaccination against flu were maintained beyond the winter season a 1
      year follow-up was conducted. METHODS AND RESULTS: During the winter season, we
      enrolled prospectively 200 myocardial infarction patients admitted in the first
      72 h, and 101 planned angioplasty/stent patients (PCI) without unstable coronary
      artery disease, prior by-pass surgery, angioplasty or tissue necrosis. Only four
      patients failed to meet the inclusion criteria. Participants were randomly
      allocated to receive flu vaccination or remain unvaccinated on top of standard
      medication (control group). The study was conducted in hospitalized patients with
      the aim to test the potential beneficial effect of flu vaccination in a secondary
      prevention scenario. Under intention to treat analysis the incidence of the
      primary end-point cardiovascular death at 1 year was significantly lower among
      patients receiving vaccination, 6% as compared with controls, 17% (relative risk
      with vaccine as compared with controls, 0.34; 95% confidence interval (CI), 0.17
      to 0.71; P=0.002). The triple composite end-point occurred in 22% of the patients
      in the vaccine group vs 37% in controls, hazard ratio 0.59, 95% CI 0.4 to 0.86)
      P=0.004. The beneficial effect was mainly detected in acute myocardial infarction
      patients (four events in the active arm vs 21 in the control group, P=0.0002 [95%
      CI 0.19, 0.07-0.53]), and Cox regression analyses revealed that there was a
      greater benefit with flu vaccination in patients at high risk according with the
      TIMI score, and those with non-ST-segment deviation myocardial infarction (95%
      CI: 0.13 [0.03-0.52]) CONCLUSIONS: Influenza vaccination may reduce the risk of
      death and ischaemic events in patients suffering from infarction and post
      angioplasty during flu season. This effect was significantly evident at 1-year
      follow-up. Larger confirmatory studies are needed to evaluate the real impact on
      flu vaccination on outcome after acute coronary syndromes.

PMID- 14683740
TI  - Intravascular ultrasound evaluation after sirolimus eluting stent implantation
      for de novo and in-stent restenosis lesions.
AB  - AIMS: The aim of this study is to compare the efficacy of sirolimus-eluting
      stents (SES) on neointimal growth and vessel remodelling for in-stent restenosis
      versus de novo coronary artery lesions using serial intravascular ultrasound
      (IVUS). METHODS AND RESULTS: The study population consisted of 86 patients with
      in-stent restenosis (ISR) (n=41) or de novo lesions (n=45) treated with SES and
      evaluated by IVUS post-procedure and at follow-up. One 18-mm SES was used for de
      novo lesions while 16 patients with ISR received >1SES (total stented length 17.9
      mm vs 22.0 mm respectively; P=0.004). At follow-up, no differences were observed
      between the ISR and de novo groups with respect to changes in the mean external
      elastic membrane (1.7% vs 1.3%; P=0.53), plaque behind the stent (1.2% vs 3.4%;
      P=0.49), and lumen areas (0.7% vs 1.9%; P=0.58). No positive remodelling or edge
      effect was observed. A gap between stents was observed in two patients with ISR,
      where more prominent, though non-obstructive, neointimal proliferation was noted.
      CONCLUSION: Sirolimus-eluting stenting is equally effective at inhibiting
      neointimal proliferation in de novo and ISR lesions without inducing edge
      restenosis or positive vascular remodelling.

PMID- 14683741
TI  - Heme oxygenase-1 gene promotor microsatellite polymorphism is associated with
      angiographic restenosis after coronary stenting.
AB  - AIMS: Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme degradation,
      leading to the generation of free iron, biliverdin, and carbon monoxide (CO). CO
      exerts potent antiproliferative and anti-inflammatory effects in the vascular
      walls, thereby influencing neointimal formation after vascular injury. A
      dinucleotide GT repeat in the promotor region of human HO-1 gene shows a length
      polymorphism that modulates the level of gene transcription. This study aimed to
      assess the association of the length of (GT)(n)repeats in HO-1 gene promotor with
      restenosis and adverse cardiac events after coronary stenting. METHODS AND
      RESULTS: Quantitative coronary angiography was evaluated before, immediately
      after and 6 months after stent implantation in 323 consecutive patients with
      successful coronary stenting. In each patient, the allele frequency of
      (GT)(n)repeats in HO-1 gene promotor was examined. Compared with those with
      shorter (S, <26) GT repeats, patients with longer (L, > or =26) GT repeats on
      either allele had more frequent angiographic restenosis with an adjusted odds
      ratio (OR) of 3.74 (95% confidence interval, 1.61 to 8.70, P=0.002). Such
      association was even more prominent in patients with small coronary arteries or
      complex lesions before stenting. Besides, carriers of L/L genotype had an
      increased risk (adjusted OR, 3.26; 95% confidence interval, 1.58 to 6.72,
      P=0.001) for adverse cardiac events during follow-up. CONCLUSIONS: The length
      polymorphism of GT repeat in HO-1 gene promoter is an independent risk factor for
      angiographic restenosis as well as adverse cardiac events after coronary
      stenting. These findings suggest the genetic contribution to stent restenosis and
      support the notion that the long dinucleotide GT repeat in promotor region may
      interfere with HO-1 gene transcription, leading to decreased vascular protection
      upon injury.

PMID- 14683742
TI  - Risk factors for coronary calcification in older subjects. The Rotterdam Coronary
      Calcification Study.
AB  - AIMS: We examined associations between cardiovascular risk factors and coronary
      calcification assessed by electron-beam tomography (EBT) in an unselected
      population of older subjects. METHODS AND RESULTS: The Rotterdam Coronary
      Calcification Study is a population-based study in subjects > =55 years.
      Participants underwent EBT scanning. Coronary calcification was quantified
      according to the Agatston score. Cardiovascular risk factors were assessed 7
      years before and concurrently to scanning. We used the first 2013 participants
      for the present analyses. Risk factors assessed 7 years before scanning were
      strongly associated with calcium score. Associations with blood pressure and
      cholesterol attenuated when measured concurrently to scanning. Although the
      number of risk factors was strongly associated with a high calcium score in
      asymptomatic subjects, 29% of the men and 15% of the women without risk factors
      had a high calcium score. CONCLUSIONS: This population-based study in older
      subjects shows that cardiovascular risk factors are associated with coronary
      calcification. Associations were stronger for risk factors measured at earlier
      age. Almost 30% of the men and 15% of the women without risk factors had
      extensive coronary calcification.

PMID- 14683743
TI  - Coronary disease in relation to social support and social class in Swedish men. A
      15 year follow-up in the study of men born in 1933.
AB  - AIMS: Low socio-economic status is a well-known risk factor for coronary heart
      disease (CHD), but the evidence concerning social network has been less
      consistent. In this prospective cohort study of men we sought to estimate the
      impact of social network factors on the risk of incident coronary heart disease
      and mortality from all causes. METHODS AND RESULTS: In a population of 741 men
      aged 50 at baseline 92 new cases of coronary disease were identified over a
      follow-up period of 15 years. Social factors included occupational class, two
      measures of social support-- "emotional attachment" and "social integration"--
      and a measure of global mental stress. Among the men in the lowest quartile of
      social integration, there were 13.6 cases (per 1000 observation years), compared
      to 8.9 in the intermediate two quartiles and 6.0 in the highest quartile (P for
      trend 0.003). After adjustment for all relevant risk factors the hazard ratio
      (HR) for the highest, compared with the lowest, quartile was 0.45 (0.24-0.84);P
      for trend 0.013. Emotional attachment was also associated with significantly
      reduced risk. The adjusted HR for the lowest quartile was 0.58 (0.37-0.91);
      P=0.019. No relation between mental stress and risk of CHD, or between low
      occupational class and risk of CHD was found. CONCLUSION: In this prospective
      study of men, we found two dimensions of low social support-low social
      integration and low emotional attachment-to be predictive of coronary morbidity,
      independently of other risk factors.

PMID- 14683744
TI  - CagA-positive cytotoxic H. pylori strains as a link between plaque instability
      and atherosclerotic stroke.
AB  - AIMS: Previous studies suggested an association between infection by cytotoxic
      CagA-positive Helicobacter pylori strains and atherosclerotic stroke. It has been
      hypothesized that CagA strains could increase the risk for stroke by affecting
      carotid plaque irregularity. Our aims were: (1) to confirm the association
      between CagA strains and atherosclerotic stroke, and (2) to assess the
      association between CagA strains and carotid plaque irregularity. METHODS AND
      RESULTS: We enrolled 105 consecutive patients affected by atherosclerotic stroke
      and 130 sex, age, social background-matched controls without relevant vascular
      diseases. Risk factors for atherosclerotic stroke, H. pylori infection and CagA
      status were evaluated in all subjects. The presence of plaque instability was
      evaluated by colour Doppler ultrasound. The prevalence of CagA-positive strains
      was significantly higher in patients than in controls (adjusted OR 2.99, 95% CI
      1.52-5.88, P=0.002). The CagA seropositivity was the only factor independently
      associated with carotid plaque irregularity (adjusted OR 8.42, 95% CI 1.58-44.64,
      P=0.004). CONCLUSION: The evidence of significant associations between CagA
      positive H. pylori strains and the presence of carotid plaque instability support
      their possible involvement in the pathophysiology of atherosclerotic stroke.

PMID- 14683745
TI  - Clinical outcomes of stents versus balloon angioplasty in non-acute coronary
      artery disease. A meta-analysis of randomized controlled trials.
AB  - AIMS: To evaluate whether stents as compared to balloon angioplasty reduce
      mortality in patients with non-acute coronary artery disease. METHODS AND
      RESULTS: We identified randomized controlled trials comparing stents to balloon
      angioplasty for the treatment of non-acute coronary artery disease by searching
      major medical databases from 1979 to March 2002. Two independent reviewers
      selected and extracted data from trials that had to report data on death and
      myocardial infarction. Nineteen trials, with a total of 8004 patients, fulfilled
      our inclusion criteria. For 1000 patients treated with stents rather than balloon
      angioplasty, 3 (95% CI 0-6), 5 (95% CI 0-9), and 6 (95% CI -1-12) additional
      lives were saved at 30 days, 6 and 12 months. At 12 months, for 1000 patients
      treated with stents rather than balloon angioplasty 46 (95% CI 25-66) additional
      target vessel revascularizations were avoided, but 25 (95% CI 15-34) additional
      bleeding complications with need for blood transfusion or surgical intervention
      occurred. In sensitivity analysis 11 (95% CI 2-20) and 2 (95% CI -4-7) deaths
      were avoided per 1000 patients treated with stents rather than PTCA in trials
      that routinely used compared to trials that did not use glycoprotein IIb/IIIa
      inhibitors. CONCLUSION: In non-acute coronary disease stents may reduce overall
      mortality, but this benefit seems to be limited to stents used in conjunction
      with glycoprotein IIb/IIIa inhibitors. Stents compared to PTCA reduce target
      vessel revascularizations, but increase the risk of bleeding complications.

PMID- 14683746
TI  - Prognostic value of clinical and morphologic findings in short-term evolution of
      aortic intramural haematoma. Therapeutic implications.
AB  - AIMS: Intramural haematoma (IMH) forms part of the acute aortic syndrome
      presenting physiopathologic and evolutive patterns different from those of aortic
      dissection. The aim of this study was to determine the mortality and predictive
      factors of IMH in the first 3 months of evolution. METHODS AND RESULTS: Sixty
      eight consecutive patients diagnosed of IMH (12 type A, 56 type B) were
      prospectively studied. Ten patients (eight type A, two type B) were surgically
      treated for clinical or haemodynamic evolution. Mortality rate was 19% (six type
      A and seven type B): five surgically treated (three type A, two type B) and eight
      medically treated (three type A, five type B). No relationship was observed
      between clinical variables and evolution. Maximum aortic diameter was greater in
      the group of patients who died (65.5+/-14.4 mm vs 46.0+/-7.6 mm; P<0.0001).
      Mortality rate in patients with aortic diameter >50 mm was 50% (P<0.0001).
      Significant periaortic bleeding was mortality-related (47%; P<0.005).
      Multivariate analysis showed only a significant relationship between mortality
      and maximum aortic diameter >50 mm (OR=11.33; P<0.005) and ascending aorta
      involvement (OR=11.18; P<0.05). CONCLUSION: Intramural haematoma mortality in the
      first 3 months of evolution is high (19%). Maximum aortic diameter >50 mm and
      ascending aorta involvement are predictive of early mortality.

PMID- 14683747
TI  - Long-term survival after pacemaker implantation. Prognostic importance of gender
      and baseline patient characteristics.
AB  - Permanent cardiac pacing is the treatment of choice in severe and symptomatic
      bradycardia. To determine factors associated with longer survival we analysed the
      survival times and baseline characteristics of 6505 patients after pacemaker
      implantation. This longitudinal study with 30 years of follow-up was performed in
      a single centre university hospital with all-cause mortality as the end-point. In
      6505 patients we analysed a total of 30948 years of patient follow-up, median
      survival was 101.9 months ( approximately 8.5 years), with 44.8% of patients
      alive after 10 years and 21.4% alive after 20 years. In all subgroups women had a
      significantly longer survival than men (118 vs 91.7 months, P<0.0001), despite a
      markedly higher age at implantation (73.2 years vs 71 years, P<0.0001). Survival
      of patients with sick-sinus-syndrome was significantly better than in patients
      with high degree AV-block, which in turn, was better than survival of patients
      with atrial fibrillation (132.9 months vs 94.2 months vs 85.1 months, P<0.0001).
      Multivariate analysis revealed several independent factors: age, gender, decade
      of implantation, type of pacemaker, index arrhythmia and initial symptoms.
      Interestingly, if only the patients of the last decade were analysed
      multivariately, neither pacing mode nor index arrhythmia were independently
      associated with survival. In conclusion, survival of patients with pacemakers is
      independently influenced by several baseline characteristics which can identify
      patients with very long survival.

PMID- 14683748
TI  - Short-term effects of atorvastatin on haemorheologic parameters, platelet
      aggregation and endothelium dysfunction in patients with hypercholesterolaemia.

PMID- 14683749
TI  - Is an additional post-myocardial infarction beta-blocker trial required in the
      era of early revascularization?

PMID- 14683750
TI  - Mortality in congestive heart failure complicated by atrial fibrillation.

PMID- 14684146
TI  - Activation of factor VIII and mechanisms of cofactor action.
AB  - The factor VIII procofactor circulates as a metal ion-dependent heterodimer of a
      heavy chain and light chain. Activation of factor VIII results from limited
      proteolysis catalyzed by thrombin or factor Xa, which binds the factor VIII
      substrate over extended interactive surfaces. The proteases efficiently cleave
      factor VIII at three sites, two within the heavy and one within the light chain
      resulting in alteration of its covalent structure and conformation and yielding
      the active cofactor, factor VIIIa. The role of factor VIIIa is to markedly
      increase the catalytic efficiency of factor IXa in the activation of factor X.
      This effect is manifested in a dramatic increase in the catalytic rate constant,
      k(cat), by mechanisms that remain poorly understood.

PMID- 14684147
TI  - Therapy for immunoglobulin light chain amyloidosis: the new and the old.
AB  - An accurate diagnosis of amyloidosis and its subtype classification are essential
      for disease prognostication and treatment. In primary amyloidosis, overall median
      survival is approximately 2 years and may be less in patients with
      cardiomyopathy. Current therapy for primary amyloidosis is suboptimal. Controlled
      studies suggest that treatment with melphalan and prednisone may provide marginal
      survival benefit. A more aggressive approach such as autologous hematopoietic
      stem cell transplantation may offer potential for long-term benefit. Although
      patients undergoing autologous hematopoietic stem cell transplantation are highly
      selected, response rates can approach 60%, and patients with amyloidosis who
      respond to treatment have potential for long-term survival. New treatment
      modalities that were shown to have antitumor activity in multiple myeloma (high
      dose dexamethasone and thalidomide) may also be of therapeutic value in primary
      amyloidosis. Systemic chemotherapy would not be expected to have any beneficial
      effect on other forms of amyloid and carries significant risk.

PMID- 14684148
TI  - The therapy of relapsed acute leukaemia in adults.
AB  - Although the cure of acute leukaemia has improved significantly, many patients
      will still relapse and die. The unraveling of the molecular pathogenesis of acute
      leukaemia has lead to the identification of new prognostic factors and improved
      the detection of minimal residual disease. The treatment of relapsed acute
      leukaemia with chemotherapy remains unsatisfactory. Allogeneic or autologous
      blood and marrow transplant (BMT) can cure a subset of patients with relapsed
      acute leukaemia. The identification of the graft-vs-leukaemia (GVL) effect has
      lead to the development of donor lymphocyte infusions to re-induce remission in
      patients with relapsed leukaemia after allogeneic BMT and also stimulated the
      development of the less toxic nonmyeloablative allogeneic transplant approach.
      The identification of molecular targets of therapy and the development of
      monoclonal antibody-directed therapy has generated optimism. It is possible that
      combinations of chemotherapy, molecularly directed therapy, and immunotherapy may
      be combined to cure an increasing proportion of patients with acute leukaemia.

PMID- 14684149
TI  - The intriguing contribution of white blood cells to sickle cell disease - a red
      cell disorder.
AB  - Sickle cell disease (SCD) is characterized by a point mutation that replaces
      adenine with thymidine in the sixth codon of the beta-globin gene, a unique
      morphological abnormality of red blood cells, vaso-occlusion with ischaemic
      tissue injury, and susceptibility to infections. Vascular lumen obstruction in
      SCD results from interaction of erythrocytes, leukocytes, platelets, plasma
      proteins, and the vessel wall. The disease phenotype is a product of various
      genes and environmental factors acting in concert with the protein lesion
      underlying the red cell anomaly. The severity of SCD increases with leukocyte
      count. The biological basis and therapeutic implications of this relationship are
      discussed. Leukocytes contribute to SCD by adhering to blood vessel walls and
      obstructing the lumen, aggregating with other blood cells with more effective
      blockage of the lumen, stimulating the vascular endothelium to increase its
      expression of ligands for adhesion molecules on blood cells, and causing tissue
      damage and inflammatory reaction which predispose to vaso-occlusion. Patients
      with impaired ability of leukocytes to kill microbes are more prone to
      infections; which precipitate sickle cell crisis. Reduction of leukocyte count
      ameliorates SCD. Similarly, targeted blockade or reduced synthesis of specific
      leukocyte adhesion molecules and their ligands might confer clinical benefit in
      SCD.

PMID- 14684150
TI  - 3D structure of the CD26-ADA complex obtained by cryo-EM and single particle
      analysis.
AB  - The specific binding of adenosine deaminase to the multifunctional membrane
      glycoprotein dipeptidyl peptidase IV is thought to be immunologically relevant
      for certain regulatory and co-stimulatory processes. In this study we present the
      3D structure of the complete CD26-ADA complex obtained by single particle cryo-EM
      at 22A resolution. ADA binding occurs at the outer edges of the beta-propeller of
      CD26. Docking calculations of available CD26 and ADA crystal data into the
      obtained EM density map revealed that the ADA-binding site is stretched across
      CD26 beta-propeller blades 4 and 5 involving the outermost distal hydrophobic
      amino acids L294 and V341 but not T440 and K441 as suggested by antibody binding.
      Though the docking of the ADA orientation appears less significant due to the
      lack of distinct surface features, non-ambiguous conclusions can be drawn in the
      combination with earlier indirect non-imaging methods affirming the crucial role
      of the ADA alpha2-helix for binding.

PMID- 14684151
TI  - Evolutionarily conserved expression pattern and trans-regulating activity of
      Xenopus p51/p63.
AB  - p51/p63, a member of the p53 gene family, is structurally conserved among a wide
      range of organisms, although the transactivator (TA) and N-terminally truncated
      (deltaN) isotype producing property seems to vary. Since p51/p63 is thought to
      play important roles in skin, limb, and craniofacial development in mammals, we
      examined Xenopus laevis larval and adult tissues for expression of p51/p63.
      Temporal analyses indicated enhanced transcription of the deltaN form of p51/p63
      in premetamorphosis phase (at stage 44-48). p51/p63-positive cells in the inner
      layer of larval skin expanded to the suprabasal layers during the stratification.
      The epithelium of limb buds and the maxillofacial ectodermal tissues in tadpoles
      had a high level expression of p51/p63. The cloned deltaN-A/gamma type Xenopus
      p51/p63 exhibited a dominant-negative activity against the human TA-A/gamma
      isotype in a reporter assay. These results suggest that tissue-specific p51/p63
      inducing mechanism and isotype-specific transcriptional regulator activities of
      p51/p63 are conserved between mammals and frogs.

PMID- 14684152
TI  - S100A16, a ubiquitously expressed EF-hand protein which is up-regulated in
      tumors.
AB  - Calcium binding proteins of the S100 family play a central role in many intra-
      and extracellular processes and abnormal expression was observed in various
      tumors and human diseases. We have identified a unique new member of this gene
      family: S100A16 which is the S100 protein widest distributed in human and which
      is highly conserved in mammals. Up-regulation of S100A16 was found in many tumors
      implying a central cellular function related to malignant transformation. The
      gene was composed of four exons, two of which alternatively initiated
      transcription. Three different transcripts suggested a complex regulation of the
      S100A16 gene. Moreover, CAG repeats were identified in the transcribed region
      which might be associated with diseases of the nervous system. All human
      transcripts encoded the same, typically small S100 protein of 103 amino acids
      containing the S100-specific motif of two distinct EF-hands. S100A16 was mapped
      within the S100 gene cluster on human chromosome 1q21, a region that is
      frequently rearranged in tumors.

PMID- 14684153
TI  - Expression of L-ornithine Ndelta-oxygenase (PvdA) in fluorescent Pseudomonas
      species: an immunochemical and in silico study.
AB  - Omega-amino acid monooxygenases (EC 1.14.13.-), catalysing the formation of
      hydroxamate precursors of microbial siderophores (e.g., pyoverdine), have so far
      eluded structural and biochemical characterisation. Here, the expression of
      recombinant L-ornithine-Ndelta-oxygenase (PvdA) from Pseudomonas aeruginosa PAO1
      is reported. A library of eight monoclonal antibodies (MAbs) directed against
      PvdA has been generated. Two MAb families recognising the N- and C-terminal
      regions of PvdA were identified. The MAbs made it possible to demonstrate that 45
      48 kDa PvdA homologues are expressed in response to iron limitation by different
      species and strains of fluorescent pseudomonads. Despite the different degrees in
      sequence similarity between P. aeruginosa PvdA and putative homologues from
      Pseudomonas fluorescens, Pseudomonas putida, Pseudomonas syringae, Burkholderia
      cepacia, and Ralstonia solanacearum, in silico domain scanning predicts an
      impressive conservation of putative cofactor and substrate binding domains. The
      MAb library was also used to monitor PvdA expression during the transition of P.
      aeruginosa from iron-sufficient to iron-deficient growth.

PMID- 14684154
TI  - Establishment of a new model of human multiple myeloma using
      NOD/SCID/gammac(null) (NOG) mice.
AB  - We developed a new experimental animal model of human multiple myeloma using
      immunodeficient NOD/SCID/gammac(null) (NOG) mice. A human myeloma cell line,
      U266, was intravenously inoculated into 20 NOG mice, all of which developed hind
      leg paralysis and distress around 6 weeks after transplantation. Pathological
      studies showed that only the bone marrow was infiltrated with U266 cells, and no
      cells were present in other organs. Osteolytic lesions in cortical bones and loss
      of trabecular bones were prominent in U266-transplanted NOG mice. In contrast,
      U266 cells were not detected in CB17scid or NOD/SCID mice 6 weeks after
      intravenous inoculation. Human IgE, produced by U266 cells, was detected in the
      serum of U266-transplanted NOG mice by ELISA. The results indicated that this hu
      myeloma NOG model might be useful for studying the pathogenesis of myeloma and
      related osteolytic lesions, and are suggestive of its applicability to the future
      development of new drugs.

PMID- 14684155
TI  - Expression of a novel secretory form (Crb1s) of mouse Crumbs homologue Crb1 in
      skin development.
AB  - Drosophila Crumbs and the mammalian homologues encoded by the Crb genes are
      transmembrane proteins required for determination of retinal cell polarity. We
      cloned a novel variant of mouse Crb1 and termed it Crb1s. Since the 3'-end of
      exon 6 remained unspliced, Crb1s coded for a short secretory protein lacking the
      transmembrane and cytoplasmic domains required for the function of Crb1. The Crb1
      expression was confined to brain and eye, whereas Crb1s was detectable in various
      tissues including skin, lung, and kidney in adult mice. Active expression of
      Crb1s, but not Crb1, was observed during the skin development, in which
      localization of the Crb1s protein was altered from the basal layer to the upper
      layers. Cultured mouse keratinocytes synthesized the Crb1s protein and secreted a
      80 kDa processed form to the supernatant. After Ca(2+)-induced differentiation,
      Crb1s became associated with focal adhesions and cell-cell contacts. Crb1s may
      play a role distinct from that of Crb1 in epidermal tissue morphogenesis.

PMID- 14684156
TI  - Esterified lipid hydroperoxide-derived modification of protein: formation of a
      carboxyalkylamide-type lysine adduct in human atherosclerotic lesions.
AB  - We have recently identified Nepsilon-azelayllysine (AZL) as a carboxyalkylamide
      type novel lysine adduct in the reaction of linoleic acid hydroperoxides with the
      lysine derivative. To examine the formation of AZL in vivo, a novel monoclonal
      antibody (mAb19D5) specific to AZL moiety was prepared. The mAb19D5 scarcely
      recognized oxidized low-density lipoprotein (oxLDL), whereas the treatment of
      oxLDL with alkali or phospholipase A2 significantly increased the
      immunoreactivity. Similarly, the immunopositive materials were detected in alkali
      or phospholipase A2-treated sections from human atherosclerotic aorta but not in
      untreated sections. These results suggest that esterified lipid hydroperoxide
      derived modification of protein may serve as one mechanism for the oxidative
      modification of LDL and subsequent formation of atherosclerotic lesions in vivo.

PMID- 14684157
TI  - Peroxisome proliferator-activated receptor delta activates fatty acid oxidation
      in cultured neonatal and adult cardiomyocytes.
AB  - Peroxisome proliferator-activated receptors (PPARalpha, -gamma and -delta) are
      nuclear receptors involved in transcriptional regulations of lipid metabolism.
      The effect of PPARalpha in regulation of cardiac fatty acid oxidation has been
      well characterized. Whether PPARdelta also independently regulates fatty acid
      oxidation in the heart remains unclear. In this study, we tested the hypothesis
      that PPARdelta activates fatty acids oxidation in cardiomyocytes through
      transcriptional activation that are independent of PPARalpha. Our results first
      indicate that PPARdelta abundantly expresses in nucleus of cardiomyocytes.
      Palmitate oxidation rates were significantly increased in both neonatal and adult
      cardiomyocytes after treatment of a PPARdelta-selective ligand (GW0742). Further
      increases of fatty acid oxidation were evident when the treatment was applied to
      cardiomyocytes overexpressing a wild type PPARdelta, but not a mutant PPARdelta
      that lacks the intact carboxyl ligand-binding domain. Furthermore, genes of fatty
      acid oxidation enzymes were significantly upregulated in cultured rat neonatal
      cardiomyocytes when exposed to GW0742. GW0742 can restore partly the expression
      of certain key genes of fatty acid oxidation in mouse adult cardiomyocytes
      isolated from PPARalpha knockout mice. Therefore, while active crosstalk between
      PPARdelta and -alpha may exist, PPARdelta regulates cardiac fatty acid oxidation
      in the heart at least partly independent of PPARalpha. We conclude that PPARdelta
      may play a key role in cardiac energy balance and may serve as a "sensor" of
      fatty acid of other endogenous ligands in controlling fatty acids oxidation
      levels in the hearts under normal and pathological conditions.

PMID- 14684158
TI  - A balanced expression of two chains of heterodimer protein, the human interleukin
      12, improves high-level expression of the protein in CHO cells.
AB  - Interleukin-12 (IL-12) comprises of p40 and p35 subunits that are encoded by
      genes on separate chromosomes and form p70 heterodimer, a bioactive protein, and
      free p40, an antagonist of IL-12. Balance expression of two subunits within cells
      would be the key for high-level of production of bioactive IL-12. Thinking about
      different expression efficiencies of two genes (p40 gene with higher efficiency),
      we selected two expression vectors with different efficiencies and inserted genes
      of p40 and p35 into them separately and co-transfected them into Chinese hamster
      ovary (CHO) cells. The high-level expression of IL-12 was obtained when p40 cDNA
      was inserted into pcDNA3 (lower expression vector) and p35 cDNA was inserted into
      pEE14 (higher expression vector), but using pEE14 for p40 cDNA and pcDNA3 for p35
      cDNA, which was opposite to the optimal design, or pEE14 or pcDNA3 for both p35
      cDNA and p40 cDNA did not obtain high-level of production of p70 heterodimer, the
      bioactive IL-12. We also observed that using two chemical reagents in
      combination, as a pressure selection method or amplification for the two vectors,
      markedly enhanced the IL-12 production, when compared with any one selection
      chemical. Our results indicated that the balance expressions of two chains of
      hetrodimer protein, such as p40 and p35 of IL-12, would be a better choice to
      obtain high-level of production of the proteins.

PMID- 14684159
TI  - Escherichia coli rpoS gene has an internal secondary translation initiation
      region.
AB  - Sigma S (sigma(s)) encoded by rpoS in Escherichia coli is a stationary phase
      specific sigma subunit of the RNA polymerase holoenzyme. Widespread among the E.
      coli K12 strains is an amber mutation that prematurely terminates sigma(s). These
      rpoSAm mutants would be expected to show no sigma(s) activity. However,
      suppressor free rpoSAm mutants retain an intermediate catalase activity, a sigma
      S controlled function. By analyzing the sequence of the rpoS gene we hypothesize
      that a 277 amino acids long delta1-53 sigma(s) of about 30 kDa can be translated
      from an internal secondary translation initiation region (STIR, AGGGAGN11GUG)
      that is located downstream of the amber codon. By cloning this rpoSAm gene,
      following the expression, function, and N-terminal sequence of this mutant
      protein, we report the presence of a functional internal STIR in E. coli rpoS,
      from where a truncated but nevertheless functional form of sigma(s) can be
      synthesized.

PMID- 14684160
TI  - Phorbol ester regulation of the human gamma-glutamyltransferase gene promoter.
AB  - In the present study the molecular mechanisms underlying tetradecanoylphorbol-13
      acetate (TPA) mediated regulation of the human gamma-glutamyltransferase (GGT)
      gene were examined. TPA challenge of HeLa cells resulted in an increase of GGT
      mRNA and enzyme activity. Deletion analysis of the promoter revealed that the 
      348 to +60 fragment was able to mediate TPA induced expression. Gel shift and
      supershift analyses showed that TPA treatment increased nuclear protein binding
      to a putative AP-1 site (-225 to -214) and that c-Jun was part of the complex.
      This AP-1 element, when cloned either in its native arrangement or as tandem
      repeat 5' of the minimal thymidine kinase promoter, mediated a significant
      increase of luciferase activity after TPA treatment of transfected HeLa cells,
      while its mutated counterpart abolished the induction. The same AP-1 element was
      able to mediate TPA induced expression in HepG2 cells. Collectively these results
      indicate that like other GSH metabolising enzymes, GGT too is a target for AP-1
      mediated regulation.

PMID- 14684162
TI  - Trehalose 6-phosphate synthase from Selaginella lepidophylla: purification and
      properties.
AB  - A protein of 440 kDa with trehalose 6-phosphate synthase activity was purified
      with only one purification step by immobilized metal affinity chromatography,
      from fully hydrated Selaginella lepidophylla plants. The enzyme was purified 50
      fold with a yield of 89% and a specific activity of 7.05 U/mg protein. This
      complex showed two additional aggregation states of 660 and 230 kDa. The three
      complexes contained 50, 67, and 115 kDa polypeptides with pI of 4.83, 4.69, and
      4.55. The reaction was highly specific for glucose 6-phosphate and UDP-glucose.
      The optimum pH was 7.0 and the enzyme was stable from pH 5.0 to 10. The enzyme
      was activated by low concentrations of Ca2+, Mg2+, K+, and Na+ and by fructose 6
      phosphate, fructose, and glucose. Proline had an inhibitory effect, while sucrose
      and trehalose up to 0.4M did not have any effect on the activity. Neither the
      substrates nor final product had an inhibitory effect.

PMID- 14684161
TI  - Selective production of rat mutant selenoprotein W with and without bound
      glutathione.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) and
      electrospray ionization mass spectrometry (ESI MS) analysis of a 6x His-tagged
      recombinant form of rat mutant selenoprotein W (RMSW) reveals that aerobic growth
      conditions primarily produce a form of RMSW without bound glutathione (10,305 Da)
      whereas anaerobic conditions produce a glutathione-bound (305 Da) form (10,610
      Da). Purification of RMSW was achieved with a procedure employing acetone
      precipitation and DEAE-cellulose chromatography, in addition to Ni-NTA agarose
      chromatography. Additional steps, including polyvalent metal ion binding (PMIB)
      resin chromatography and CM-cellulose chromatography, were necessary after
      elution from the Ni-NTA agarose column, in order to maintain solubility of the
      purified protein.

PMID- 14684163
TI  - A novel MET-interacting protein shares high sequence similarity with RanBPM, but
      fails to stimulate MET-induced Ras/Erk signaling.
AB  - MET is a receptor protein tyrosine kinase for hepatocyte growth factor, a
      multifunctional cytokine controlling cell growth, morphogenesis, and motility. In
      our previous study, RanBPM/RanBP9, whose name originated from its ability to
      interact with Ran, was identified as a MET-interacting protein. RanBPM/RanBP9
      activates the Ras/Erk signaling pathway by serving as an adaptor protein of MET
      to recruit Sos. In this study, we identify a protein sharing a high amino acid
      sequence identity with RanBPM/RanBP9, especially in its SPRY domain, the region
      responsible for MET binding. This protein lacks the N-terminal poly-proline and
      poly-glutamine (Poly-PQ) stretch present in RanBPM/RanBP9 and has less homology
      with RanBPM/RanBP9 in its mid-region. We subsequently named this protein RanBP10
      after demonstrating its interaction with Ran. We show that, like RanBPM/RanBP9,
      RanBP10 interacts with the tyrosine kinase domain of MET via its SPRY domain and
      these two proteins can compete with each other to bind to MET. Interestingly,
      unlike RanBPM/RanBP9, overexpression of RanBP10 cannot induce Erk1/2
      phosphorylation and serum response element-luciferase (SRE-LUC) reporter gene
      expression. More importantly, co-transfection of RanBPM/RanBP9 and RanBP10
      significantly represses SRE-LUC reporter gene expression induced by
      overexpression of RanBPM/RanBP9. Additional binding assays demonstrate that
      RanBP10 fails to interact with Sos, which explains its inability to activate the
      Ras/Erk pathway. Furthermore, we show that the N-terminus of RanBPM/RanBP9 with
      the Poly-PQ stretch is required for recruiting Sos and a truncated RanBPM/RanBP9
      lacking this region fails to recruit Sos, indicating that the functional
      difference between RanBP10 and RanBPM/RanBP9 lies in their sequence difference in
      their N-termini.

PMID- 14684164
TI  - The functional mapping of long-range transcription control elements of the HOX11
      proto-oncogene.
AB  - Mapping of transcriptional control elements normally depends on the generation of
      a series of deletion mutants. The consequences of particular deletions are then
      functionally assessed by their ability to alter gene expression. The information
      derived from such investigations provides a general regulatory profile of the
      gene of interest, as well as generating a focus for future experiments. Due to
      the limitations of conventional DNA cloning methods, it has previously not been
      possible to use such an approach to rapidly assess the role of long-range
      regulatory elements that frequently lie further than 20 kb away from the coding
      region. In order to identify regulatory elements of the proto-oncogene HOX11 that
      may be mutated in a subset of childhood T-cell acute lymphoblastic leukaemia
      specimens, we generated nested deletions from a P1 artificial chromosome (PAC).
      This clone contained 95 kilobases (kb) of the HOX11 locus at 10q24; including 63
      kb of 5' regulatory DNA. The deletion series was produced by the use of a
      recombination based cloning system and clones were subsequently transfected into
      mammalian cells. We have identified several long-range regulatory elements that
      mediate transcriptional control of HOX11. This approach is simple, rapid, and
      inexpensive. Furthermore, it generates multiple deletion clones in a single
      experiment. This novel approach opens up a new avenue for investigating long
      range transcription control. Additionally, by allowing analysis of these elements
      in the natural context of large integrants the approach does not require the use
      of artificial extrachromosomal elements. This methodology can be applied to any
      gene cloned into a PAC or BAC vector and could also be useful in identifying
      appropriately sized deletion mutants for functional testing in transgenic models.

PMID- 14684165
TI  - Nucleic acid sequence-based amplification methods to detect avian influenza
      virus.
AB  - Infection of poultry with highly pathogenic avian influenza virus (AIV) can be
      devastating in terms of flock morbidity and mortality, economic loss, and social
      disruption. The causative agent is confined to certain isolates of influenza A
      virus subtypes H5 and H7. Due to the potential of direct transfer of avian
      influenza to humans, continued research into rapid diagnostic tests for influenza
      is therefore necessary. A nucleic acid sequence-based amplification (NASBA)
      method was developed to detect a portion of the haemagglutinin gene of avian
      influenza A virus subtypes H5 and H7 irrespective of lineage. A further NASBA
      assay, based on the matrix gene, was able to detect examples of all known
      subtypes (H1-H15) of avian influenza virus. The entire nucleic acid isolation,
      amplification, and detection procedure was completed within 6h. The dynamic range
      of the three AIV assays was five to seven orders of magnitude. The assays were
      sensitive and highly specific, with no cross-reactivity to phylogenetically or
      clinically relevant viruses. The results of the three AIV NASBA assays correlated
      with those obtained by viral culture in embryonated fowl's eggs.

PMID- 14684166
TI  - Mapping cooperative activity of the hepatitis C virus RNA-dependent RNA
      polymerase using genotype 1a-1b chimeras.
AB  - The nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) encodes an RNA
      dependent RNA polymerase (RdRp) which is essential for viral replication. NS5B
      expression in bacteria generated 20- to 50-fold lower yield and 100-fold less
      product per mol of enzyme for gentoype 1a RdRp than type 1b. Further, unlike type
      1b RdRp, type 1a enzyme failed to exhibit cooperative properties in the assays
      described herein. Differences in thermal stability may partially account for the
      inability to efficiently oligomerize. Superose gel filtration analyses confirm
      differences between these RdRp preparations, although affinity for the column
      rather than size may account for the differences in migration. To further address
      this complexity, a panel of RdRp type 1a-type 1b chimeras were evaluated and
      implicate a role for the thumb subdomain of genotype 1b RdRp as critical for
      cooperative function.

PMID- 14684167
TI  - Nuclear export of signal recognition particle RNA in mammalian cells.
AB  - In mammalian cells the signal recognition particle (SRP) consists of a
      approximately 300 nucleotide RNA and six proteins. Although the molecular
      structure and functional cycle of the SRP are both very well understood, far less
      is known about how the SRP is first assembled in the cell. Recent work has
      suggested that SRP assembly begins in the nucleoli. When NRK (rat fibroblast)
      cells were treated with leptomycin B (LMB), a specific inhibitor of the CRM1
      nuclear export receptor, the level of SRP RNA increased in the nucleoli, as did
      the level of nucleolar 28S ribosomal RNA. Moreover, when a hamster cell line
      carrying a temperature-sensitive mutation in the guanine nucleotide exchange
      factor of the GTPase Ran (Ran-GEF) was shifted to the non-permissive temperature,
      the nucleolar level of SRP RNA increased. These results indicate that the steady
      state concentration of SRP RNA in the nucleolus is sensitive to perturbations in
      nuclear import/export pathways.

PMID- 14684168
TI  - Interaction of fusogenic peptides with an antisense oligonucleotide in solution
      and in the presence of micelles: conformational studies.
AB  - The conformational effect of the interaction between various fusogenic peptides
      and an 18mer single stranded antisense oligonucleotide (ODN), targeted towards
      the green fluorescent protein mRNA, has been studied by circular dichroism
      spectroscopy in water and in the presence of anionic lysolipid micelles. The
      peptides used were the third helix of Antennapedia homeodomain pAntp-(43-58), the
      flock house virus FHV-gamma-(364-407) peptide, and its N-terminal gamma1-(364
      384) and C-terminal gamma2-(390-407) fragments. The most significant
      conformational changes were observed in ODN-pAntp-(43-58) and ODN-FHV-gamma2
      complexes. The pAntp-(43-58) forms a complex with ODN through electrostatic
      interaction resulting in profound changes in the conformation of both the peptide
      and the ODN. In the case of FHV-gamma2 peptide the complex formation takes place
      without altering the structure of ODN, and the decreased ratio of
      deltaepsilon208/deltaepsilon222 reflects the insertion of the complexed peptide
      into the micelle.

PMID- 14684169
TI  - H2S generated by heart in rat and its effects on cardiac function.
AB  - Hydrogen sulfide (H2S), which was considered as a novel gasotransmitter, is
      produced endogenously from L-cysteine in mammalian brain and vessels, and might
      be a physiological function regulator to these organs. Here, we showed that mRNA
      for H2S producing enzyme, cystathionine gamma-lyase, was expressed in myocardial
      tissues and H2S could endogenously be produced in myocardial tissues. Negative
      inotropic effect of H2S was proved in present study in vitro and in vivo
      experiments, and the effect could partly be blocked by glibenclamide, a KATP
      channel blocker. An intravenous bolus injection of NaHS provoked a decrease in
      central venous pressure. The present findings suggested that H2S could be
      endogenously produced by heart tissues, as a physiological cardiac function
      regulator, mediated by KATP channel pathway.

PMID- 14684170
TI  - Arabidopsis stress-inducible gene for arginine decarboxylase AtADC2 is required
      for accumulation of putrescine in salt tolerance.
AB  - Arginine decarboxylase (ADC) catalyzes the first step of polyamine (PA)
      biosynthesis to produce putrescine (Put) from arginine (Arg). One of the 2
      Arabidopsis ADC genes, AtADC2, is induced in response to salt stress causing the
      accumulation of free Put. To analyze the roles of stress-inducible AtADC2 gene
      and endogenous Put in stress tolerance, we isolated a Ds insertion mutant of
      AtADC2 gene (adc2-1) and characterized its phenotypes under salt stress. In the
      adc2-1 mutant, free Put content was reduced to about 25% of that in the control
      plants and did not increase under salt stress. Furthermore, the adc2-1 mutant was
      more sensitive to salt stress than the control plants. The stress sensitivity of
      adc2-1 was recovered by the addition of exogenous Put. These results indicate
      that endogenous Put plays an important role in salt tolerance in Arabidopsis.
      AtADC2 is a key gene for the production of Put under not only salinity
      conditions, but also normal conditions.

PMID- 14684172
TI  - Effects of liver failure on the enzymes in the branched-chain amino acid
      catabolic pathway.
AB  - Branched-chain alpha-keto acid dehydrogenase (BCKDH) complex catalyzes the
      committed step of the catabolism of branched-chain amino acids (BCAA). The liver
      cirrhosis chemically induced in rats raised the activity of hepatic BCKDH complex
      and decreased plasma BCAA and branched-chain alpha-keto acid concentrations,
      suggesting that the BCAA requirement is increased in liver cirrhosis. Since the
      effects of liver cirrhosis on the BCKDH complex in human liver are different from
      those in rat liver, further studies are needed to clarify the differences between
      rats and humans. In the valine catabolic pathway, crotonase and beta
      hydroxyisobutyryl-CoA hydrolase are very important to regulate the toxic
      concentration of mitochondrial methacrylyl-CoA, which occurs in the middle part
      of valine pathway and highly reacts with free thiol compounds. Both enzyme
      activities in human and rat livers are very high compared to that of BCKDH
      complex. It has been found that both enzyme activities in human livers were
      significantly reduced by liver cirrhosis and hepatocellular carcinoma, suggesting
      a decrease in the capability to dispose methacrylyl-CoA. The findings described
      here suggest that alterations in hepatic enzyme activities in the BCAA catabolism
      are associated with liver failure.

PMID- 14684173
TI  - Pharmacological activities of branched-chain amino acids: specificity of tissue
      and signal transduction.
AB  - Branched-chain amino acid (BCAA: Leu, Ile, and Val) mixture has been used for
      treatment of hypoalbuminemia in patients with decompensated liver cirrhosis in
      Japan. It has been known that BCAA, especially leucine, activates mTOR signals
      and inhibition of protein degradation results in promoting protein synthesis in
      vitro. Furthermore, leucine activates glycogen synthase via mTOR signals in L6
      cell, but not hepatocyte, and it has been shown that leucine improved glucose
      metabolism in normal and cirrhosis model rats. In this review, it will be
      proposed about the pharmacological activity of branched-chain amino acids, mainly
      leucine, on tissue specificity of cirrhotic disease.

PMID- 14684174
TI  - Mechanisms responsible for regulation of branched-chain amino acid catabolism.
AB  - The branched-chain amino acids (BCAAs) are essential amino acids and therefore
      must be continuously available for protein synthesis. However, BCAAs are toxic at
      high concentrations as evidenced by maple syrup urine disease (MSUD), which
      explains why animals have such an efficient oxidative mechanism for their
      disposal. Nevertheless, it is clear that leucine is special among the BCAAs.
      Leucine promotes global protein synthesis by signaling an increase in
      translation, promotes insulin release, and inhibits autophagic protein
      degradation. However, leucine's effects are self-limiting because leucine
      promotes its own disposal by an oxidative pathway, thereby terminating its
      positive effects on body protein accretion. A strong case can therefore be made
      that the proper leucine concentration in the various compartments of the body is
      critically important for maintaining body protein levels beyond simply the need
      of this essential amino acid for protein synthesis. The goal of the work of this
      laboratory is to establish the importance of regulation of the branched chain
      alpha-ketoacid dehydrogenase complex (BCKDC) to growth and maintenance of body
      protein. We hypothesize that proper regulation of the activity state of BCKDC by
      way of its kinase (BDK) and its phosphatase (BDP) is critically important for
      body growth, tissue repair, and maintenance of body protein. We believe that
      growth and protection of body protein during illness and stress will be improved
      by therapeutic control of BCKDC activity. We also believe that it is possible
      that the negative effects of some drugs (PPAR alpha ligands) and dietary
      supplements (medium chain fatty acids) on growth and body protein maintenance can
      be countered by therapeutic control of BCDKC activity.

PMID- 14684175
TI  - Amino acid signalling and the integration of metabolism.
AB  - It has become clear in recent years that amino acids are not only important as
      substrates for various metabolic pathways but that they can also activate a
      nutrient-sensitive, mTOR-mediated, signalling pathway in synergy with insulin.
      Leucine is the most effective amino acid in this regard. The signalling pathway
      is antagonised by AMP-activated protein kinase. Amino acid signalling stimulates
      protein synthesis and inhibits (autophagic) proteolysis. In addition, many amino
      acids cause an increase in cell volume. Cell swelling per se stimulates synthesis
      of protein, glycogen, and lipid, in part by further stimulating signalling and in
      part by unrelated mechanisms. Amino acids also stimulate signalling in beta-cells
      and stimulate beta-cell growth and proliferation. This results in increased
      production of insulin, which enhances the anabolic (and anti-catabolic)
      properties of amino acids. Finally, amino acid-dependent signalling controls the
      production of leptin by adipocytes, and thus contributes to the regulation of
      appetite.

PMID- 14684176
TI  - Branched-chain amino acids as a protein- and energy-source in liver cirrhosis.
AB  - Protein-energy malnutrition (PEM) is a common manifestation in cirrhotic patients
      with reported incidences as high as 65-90%. PEM affects largely the patients'
      quality of life and survival. Thus, diagnosis of and intervention for PEM is
      important in the clinical management of liver cirrhosis. Supplementation with
      branched-chain amino acids (BCAA) is indicated to improve protein malnutrition.
      As an intervention for energy malnutrition, frequent meal or late evening snack
      has been recently recommended. Plasma amino acid analysis characterizes the
      patients with liver cirrhosis to have decreased BCAA. Such reduction of BCAA is
      explained by enhanced consumption of BCAA for ammonia detoxication and for energy
      generation. Supplementation with BCAA raises in vitro the synthesis and secretion
      of albumin by cultured rat hepatocytes without affecting albumin mRNA expression.
      BCAA recover the impaired turnover kinetics of albumin both in rat cirrhotic
      model and in cirrhotic patients. Longer-term supplementation with BCAA raises
      plasma albumin, benefits quality of life issues, and finally improves survival in
      liver cirrhosis. Recent interests focused on the timing of administration of
      BCAA, since daytime BCAA are usually consumed by energy generation for physical
      exercise of skeletal muscles. Nocturnal BCAA seem to be more favorable as a
      source of protein synthesis by giving higher nitrogen balance. This minireview
      focuses on the basic and clinical aspects of BCAA as a pharmaco-nutritional
      source to control PEM in liver cirrhosis.

PMID- 14684177
TI  - Significance of branched chain amino acids as possible stimulators of hepatocyte
      growth factor.
AB  - Amino acids can serve as regulatory molecules that modulate numerous cellular
      functions. Branched chain amino acids (BCAAs) are known to exert influences on
      cellular metabolism, amino acid transport, protein turn over, and gene
      expression. However, the mechanisms involved in the specific effect of BCAAs have
      not been clarified. BCAA supplementation therapy is a current treatment for
      patients with liver cirrhosis, therefore, specific BCAA activities should be
      examined. Hepatocyte growth factor (HGF) is considered to be a pleiotropic
      factor, and is reported to modulate gene expression and to stimulate the
      proliferation and functions of many cell types, including hepatocytes. A
      potential application of HGF for several types of diseases has been postulated.
      Here, we describe the potential of BCAAs as a therapeutic agent that acts through
      the induction of HGF production in the liver.

PMID- 14684178
TI  - Regulation of protein synthesis by branched-chain amino acids in vivo.
AB  - Recent advances in the understanding of mRNA translation have facilitated
      molecular studies on the regulation of protein synthesis by nutrients and the
      interplay between nutrients and hormonal signals. Numerous reports have
      established that, in skeletal muscle, the branched-chain amino acids (BCAAs) have
      the unique ability to initiate signal transduction pathways that modulate
      translation initiation. Of the BCAAs, leucine is the most potent. Oral
      administration of leucine to food-deprived rats enhances muscle protein
      synthesis, in part, through activation of the mRNA binding step of translation
      initiation. Interestingly, leucine signaling in skeletal muscle differs from that
      in liver, suggesting that the responses may be tissue specific. The purpose of
      this paper was to briefly review the current knowledge of how BCAAs act as
      regulators of protein synthesis in physiologically important tissues, with
      particular focus on the mechanisms by which BCAAs regulate translation
      initiation.

PMID- 14684179
TI  - Regulation of global and specific mRNA translation by oral administration of
      branched-chain amino acids.
AB  - The importance of branched-chain amino acids as nutrient regulators of protein
      synthesis in skeletal muscle was recognized more than 20 years ago. Of the
      branched-chain amino acids, leucine in particular was shown to play a central
      role in promoting muscle protein synthesis. However, it was only recently that
      the mechanism(s) involved in the stimulation of protein synthesis by leucine has
      begun to be defined. Studies performed in our laboratory during the past few
      years have revealed that oral administration of leucine to fasted rats enhances
      protein synthesis in association with increased phosphorylation of two proteins
      downstream of the protein kinase referred to as the mammalian target of rapamycin
      (mTOR). These proteins, eukaryotic initiation factor eIF4E binding protein (4E
      BP)1 and ribosomal protein S6 kinase S6K1, control in part the step in
      translation initiation involving the binding of mRNA to the 40S ribosomal
      subunit. In theory the translation of all mRNAs can be regulated through such
      mechanisms, however, some mRNAs are more sensitive to the changes than others,
      resulting in modulation of gene expression through altered patterns of
      translation of specific mRNAs. Moreover, although a basal amount of plasma
      insulin is required for leucine to enhance signaling downstream of mTOR, the
      concentration observed in plasma of fasted rats is sufficient to observe maximal
      changes in phosphorylation of 4E-BP1 and S6K1.

PMID- 14684180
TI  - mTOR-mediated regulation of translation factors by amino acids.
AB  - The mammalian-target-of-rapamycin (mTOR) is a multidomain protein that is
      important in regulating several components of the translational machinery. mTOR
      signalling is stimulated by hormones (e.g., insulin) and by amino acids. Our
      recent data suggest that TOR signalling responds to intracellular amino acids
      rather than to external amino acid levels. The translational repressor eukaryotic
      initiation factor 4E-binding protein 1 (4E-BP1) is regulated through mTOR and
      undergoes phosphorylation at multiple sites, which affects its function. It
      contains two regulatory motifs: the C-terminal TOS motif interacts with the mTOR
      binding partner, raptor, and mediates phosphorylation of specific sites in 4E
      BP1. However, the N-terminal RAIP motif affects a larger range of mTOR-regulated
      sites. Since this motif does not bind raptor, mTOR must signal to 4E-BP1 via
      additional mechanisms that are independent of raptor. The kinase that
      phosphorylates and inhibits elongation factor 2 (eEF2 kinase) is inactivated by
      insulin via mTOR. Insulin decreases the ability of eEF2 kinase to bind
      calmodulin, its essential activator, and this effect requires mTOR signalling and
      a novel phosphorylation site in eEF2 kinase, Ser78. Ser78 is not phosphorylated
      by known components of the mTOR pathway implying the existence of novel mTOR
      regulated kinases that control eEF2 kinase.

PMID- 14684181
TI  - Raptor, a binding partner of target of rapamycin.
AB  - The mammalian target of rapamycin (mTOR) controls cell growth in response to
      amino acids and growth factors, in part by regulating p70 S6 kinase alpha (p70
      alpha) and eukaryotic initiation factor 4E binding protein 1 (4EBP1). Raptor
      (regulatory associated protein of mTOR) is a 150 kDa mTOR binding protein that is
      essential for TOR signaling in vivo and also binds 4EBP1 and p70alpha through
      their respective TOS (TOR signaling) motifs, a short conserved segment previously
      shown to be required for amino acid- and mTOR-dependent regulation of these
      substrates in vivo. Raptor appears to serve as an mTOR scaffold protein, the
      binding of which to the TOS motif of mTOR substrates is necessary for effective
      mTOR-catalyzed phosphorylation. Further understanding of regulation of the mTOR
      raptor complex in response to the nutritional environment would require
      identification of the interplay between the mTOR-raptor complex and its upstream
      effectors such as the protein products of tumor suppressor gene tuberous
      sclerosis complexes 1 and 2, and the Ras-related small G protein Rheb.

PMID- 14684182
TI  - mTOR integrates amino acid- and energy-sensing pathways.
AB  - The AMP-activated protein kinase (AMPK) exists as a heterotrimetric complex
      comprising a catalytic alpha subunit and non-catalytic beta and gamma subunits.
      Under conditions of hypoxia, exercise, ischemia, heat shock, and low glucose,
      AMPK is activated allosterically by rising cellular AMP and by phosphorylation of
      the catalytic alpha subunit. The mammalian target of rapamycin (mTOR) controls
      cellular functions in response to amino acids and growth factors. Recent reports
      including our study have demonstrated the possible interplay between mTOR and
      AMPK signaling pathways, supporting a model in which mitochondrial dysfunction
      caused by the mitochondrial inhibitors or ATP depletion inhibits activation of
      p70 S6 kinase alpha (p70alpha), a downstream effector of mTOR, by activating
      AMPK. Leucine may stimulate p70alpha phosphorylation via mTOR pathway, in part,
      by serving both as a mitochondrial fuel through oxidative carboxylation and an
      allosteric activation of glutamate dehydrogenase. This hypothesis may support an
      idea in which leucine modulates mTOR function, in part by regulating
      mitochondrial function and AMPK. Further understanding of the role of mTOR in
      coordinating amino acid- and energy-sensing pathways would provide new insights
      into relationship between nutrients and cellular functions.

PMID- 14684183
TI  - Amino acids as regulators of gene expression: molecular mechanisms.
AB  - Regulation of gene expression by nutrients in mammals is an important mechanism
      allowing them to adapt their physiological functions according to the supply of
      nutrient in the diet. It has been shown recently that amino acids are able to
      regulate by themselves the expression of numerous genes. CHOP, asparagine
      synthetase, and IGFBP-1 regulation following AA starvation will be described in
      this review with special interest in the molecular mechanisms involved.

PMID- 14684184
TI  - Autophagy: a regulated bulk degradation process inside cells.
AB  - Autophagy is a major intracellular degradation/recycling system ubiquitous in
      eukaryotic cells. It contributes to the turnover of cellular components by
      delivering portions of the cytoplasm and organelles to lysosomes, where they are
      digested. Autophagy is mediated by membrane trafficking of unique double-membrane
      structures, the so-called autophagosomes, which are formed transiently. Moreover,
      autophagy is dramatically induced under starvation conditions to maintain an
      amino acid pool so that essential proteins may be synthesized. Recent studies
      have revealed insights into the molecular basis of membrane dynamics and the
      regulation of autophagy, which had remained cryptic for a long time.

PMID- 14684185
TI  - External respiratory motion for abdominal radiotherapy patients: implications for
      patient alignment.
AB  - Conformal external beam radiotherapy relies on accurate spatial positioning of
      the tumor and normal tissues during treatment. For abdominal patients, this is
      complicated by the motion of internal organs and the external patient contour due
      to respiration. As external motion influences the degree of accuracy achievable
      in patient setup, this motion was studied to provide indication of motions
      occurring during treatment, as well as to assess the technique of breath-holding
      at exhale (B-HEX). The motion of external abdominal points (anterior and right
      lateral) of a series of volunteers was tracked in real-time using an infrared
      tracking system, with the volunteers in treatment position. The resulting motion
      data was assessed to evaluate (1) the change in position of each point per
      breath/breath-hold, (2) the change in position between breaths/breath-holds, and
      (3) the change in position across the whole recording time. Analysis shows that,
      for the anterior abdominal point, there is little difference in the variation of
      position with time for free-breathing as opposed to the B-HEX technique. For the
      lateral point however, the B-HEX technique reduces the motion during each
      treatment cycle (i.e., during the breath-hold) and over an extended period (i.e.,
      during a series of breath-holds). The B-HEX technique thus provides greater
      accuracy for setup to lateral markers and provides the opportunity to reduce
      systematic and random localization errors.

PMID- 14684186
TI  - Exploring the effect of marked normal structure volume on normal tissue
      complication probability.
AB  - Radiation therapy dosimetry software now frequently incorporates biological
      predictions of the probability of normal tissue complications. This study
      investigates whether the length of normal structure outlined affects a normal
      tissue complication probability (NTCP) for that structure. It also researches the
      effect of any change in the dose parameter used to produce a 50% probability of a
      complication (the TD50) on the calculated NTCP, as this is related to the
      clinical observations. An NTCP was calculated for rectum and bladder on a sample
      of prostate cases receiving external beam radiation therapy. The length of the
      organs at risk was varied and the NTCP recalculated for each different length
      using the same treatment plan. Large variations of up to 80% in NTCP for
      different delineated lengths of organ for a given TD50 were observed. Changing
      the TD50 dose altered the calculated NTCP and the relative size of the variation
      in the values. This parameter will need further investigation; a standardized
      delineated length of 2 cm beyond the beam edge for normal structures is
      recommended. Interpatient and interinstitution plan comparison using dose volume
      histograms and/or normal tissue complication probabilities will be compromised
      until such standardization occurs.

PMID- 14684187
TI  - Monte Carlo dose calculations in the treatment of a pelvis with implant and
      comparison with pencil-beam calculations.
AB  - In the present paper, dose distribution calculated with the Monte Carlo code EGS4
      and with a pencil-beam algorithm are compared for the treatment of a pelvis with
      an implant. Overestimations of dose values inside the target volume by the pencil
      beam algorithm of up to 10% were found, which are attributed to the
      underestimation of the absorption of photons by the implant. The differences in
      dose distributions are also expressed by comparing the tumor control probability
      (TCP) of the Monte Carlo dose calculations with the TCP of the pencil-beam
      calculations. A TCP reduction of order of 30% was found.

PMID- 14684188
TI  - A systematic benchmark method for analysis and comparison of IMRT treatment
      planning algorithms.
AB  - Tools and procedures for evaluating and comparing different intensity-modulated
      radiation therapy (IMRT) systems are presented. IMRT is increasingly in demand
      and there are numerous systems available commercially. These programs introduce
      significantly different software to dosimetrists and physicists than conventional
      planning systems, and the options often seem initially overwhelmingly complex to
      the user. By creating geometric target volumes and critical normal tissues, the
      characteristics of the algorithms may be investigated, and the influence of the
      different parameters explored. Overall optimization strategies of the algorithm
      may be characterized by treating a square target volume (TV) with 2 perpendicular
      beams, with and without heterogeneities. A half-donut (hemi-annulus) TV with a
      "donut hole" (central cylinder) critical normal tissue (CNT) on a CT of a
      simulated quality assurance phantom is suggested as a good geometry to explore
      the IMRT algorithm parameters. Using this geometry, the order of varying
      parameters is suggested. First is to determine the effects of the number of
      stratifications of optimized intensity fluence on the resulting dose
      distribution, and selecting a fixed number of stratifications for further
      studies. To characterize the dose distributions, a dose-homogeneity index (DHI)
      is defined as the ratio of the dose received by 90% of the volume to the minimum
      dose received by the "hottest" 10% of the volume. The next step is to explore the
      effects of priority and penalty on both the TV and the CNT. Then, choosing and
      fixing these parameters, the effects of varying the number of beams can be looked
      at. As well as evaluating the dose distributions (and DHI), the number of
      subfields and the number of monitor units required for different numbers of
      stratifications and beams can be evaluated.

PMID- 14684189
TI  - An innovative dosimetric model for formulating a semi-analytical solution for the
      activity-volume relationship in prostate implants.
AB  - An innovative (and yet simple) dosimetric model is proposed that provides a semi
      analytical solution to the total activity-volume relationship in ultrasound
      guided transperineal prostate implant. This dosimetric model is based on 4 simple
      assumptions. First, the prostate target volume is approximated as a sphere.
      Second, the urethra is presumed to transverse through the center of the prostate
      target volume. Third, peripheral loading is applied as the seed-loading
      technique. Fourth, as the major innovation of the proposed model, the radial dose
      function of the Iodine-125 125I seed is forced to fit a simple power function of
      the distance r. Pursuant to the third assumption, the peripherally-loaded seeds
      also define a spherical volume defined as the loading volume w. Also pursuant to
      the fourth assumption, the radial dose function is expressed as 1.139*r(-0.474)
      for r = 1.5 to 2.5 cm. Thereafter, a simple analytical power-law equation, A =
      1.630* w(0.825), for the relationship between the total activity A in mCi and the
      loading volume w in cc is derived for 125I monotherapy. Isodose plans for loading
      volumes corresponding to r = 1.5, 1.8, 2.2, and 2.5 cm were performed. The
      maximal isodose coverage volume maxV100 was calculated for each case and was
      found to be on the average 65% larger than the loading volume w. Matching
      prostate target volume V to the loading volume w therefore yields a generous
      implant (with a margin of approximately 3.3 mm). Conversely, matching the
      prostate target volume V to the maxV100 yields a tight implant (with 0.0 mm or no
      margin). Matching the prostate target volume V to a midpoint between the loading
      volume w and maxV100 yields a moderate implant (with approximately 1- to 2-mm
      margin). Three individual equations are derived for each type of implants: A =
      1.630* V(0.825), A = 1.288* V(0.825), or A = 1.078 V(0.825) for generous, tight,
      or moderate implants, respectively. Patient data at the Chicago Prostate Cancer
      Center are found to support the above dosimetric model and the 3 semi
      analytically derived equations. The above equations are also compared favorably
      with some of the previously published equations from other authors. These results
      support the efficacy of the proposed dosimetric model.

PMID- 14684190
TI  - Dosimetric quality endpoints for low-dose-rate prostate brachytherapy using
      biological effective dose (BED) vs. conventional dose.
AB  - The purpose of this study was to compare conventional low-dose-rate prostate
      brachytherapy dosimetric quality parameters with their biological effective dose
      (BED) counterparts. To validate a model for transformation from conventional dose
      to BED, the postimplant plans of 31 prostate brachytherapy patients were
      evaluated using conventional dose-volume histogram (DVH) quality endpoints and
      analogous BED-DVH endpoints. Based on CT scans obtained 4 weeks after
      implantation, DVHs were computed and standard dosimetric endpoints V100 (volume
      receiving 100% of the prescribed dose), V150, V200, HI (1-[V150/V100]), and D90
      (dose that 90% of the target volume received) were obtained for quality analysis.
      Using known and reported transformations, dose grids were transformed to BED
      early (alpha/beta = 10 Gy) and BED-late (alpha/beta = 3 Gy) grids, and the same
      dosimetric endpoints were analyzed. For conventional, BED-early and BED-late
      DVHs, no differences in V100 were seen (0.896, 0.893, and 0.894, respectively).
      However, V150 and V200 were significantly higher for both BED-early (0.582 and
      0.316) and BED-late (0.595 and 0.337), compared with the conventional (0.539 and
      0.255) DVHs. D90 was significantly lower for the BED-early (103.1 Gy) and BED
      late transformations (106.9 Gy) as compared with the conventional (119.5 Gy)
      DVHs. The conventional prescription parameter V100 is the same for the
      corresponding BED-early and BED-late transformed DVHs. The toxicity parameters
      V150 and V200 are slightly higher using the BED transformations, suggesting that
      the BED doses are somewhat higher than predicted using conventional DVHs. The
      prescription/quality parameter D90 is slightly lower, implying that target
      coverage is lower than predicted using conventional DVHs. This methodology can be
      applied to analyze BED dosimetric endpoints to improve clinical outcome and
      reduce complications of prostate brachytherapy.

PMID- 14684191
TI  - Comparison of intensity-modulated radiotherapy with three-dimensional conformal
      radiation therapy planning for glioblastoma multiforme.
AB  - This study was designed to assess the feasibility and potential benefit of using
      intensity-modulated radiotherapy (IMRT) planning for patients newly diagnosed
      with glioblastoma multiforme (GBM). Five consecutive patients with confirmed
      histopathologically GBM were entered into the study. These patients were planned
      and treated with 3-dimensional conformal radiation therapy (3DCRT) using our
      standard plan of 3 noncoplanar wedged fields. They were then replanned with the
      IMRT method that included a simultaneous boost to the gross tumor volume (GTV).
      The dose distributions and dose-volume histograms (DHVs) for the planning
      treatment volume (PTV), GTV, and the relevant critical structures, as obtained
      with 3DCRT and IMRT, respectively, were compared. In both the 3DCRT and IMRT
      plans, 59.4 Gy was delivered to the GTV plus a margin of 2.5 cm, with doses to
      critical structures below the tolerance threshold. However, with the simultaneous
      boost in IMRT, a higher tumor dose of approximately 70 Gy could be delivered to
      the GTV, while still maintaining the uninvolved brain at dose levels of the 3DCRT
      technique. In addition, our experience indicated that IMRT planning is less labor
      intensive and time consuming than 3DCRT planning. Our study shows that IMRT
      planning is feasible and efficient for radiotherapy of GBM. In particular, IMRT
      can deliver a simultaneous boost to the GTV while better sparing the normal brain
      and other critical structures.

PMID- 14684192
TI  - Evaluation of two water-equivalent phantom materials for output calibration of
      photon and electron beams.
AB  - Two commercially available water-equivalent solid phantom materials were
      evaluated for output calibration in both photon (6-15 MV) and electron (6-20 MeV)
      beams. The solid water 457 and virtual water materials have the same chemical
      composition but differ in manufacturing process and density. A Farmer-type
      ionization chamber was used for measuring the output of the photon beams at 5-
      and 10-cm depth and electron beams at maximum buildup depth in the solid phantoms
      and in natural water. The water-equivalency correction factor for the solid
      materials is defined as the ratio of the chamber reading in natural water to that
      in the solid at the same linear depth. For photon beams, the correction factor
      was found to be independent of depth and was 0.987 and 0.993 for 6- and 15-MV
      beams, respectively, for solid water. For virtual water, the corresponding
      correction factors were 0.993 and 0.998 for 6- and 15-MV beams, respectively. For
      electron beams, the correction factors ranged from 1.013 to 1.007 for energies of
      6 to 20 MeV for both solid materials. This indicated that the water-equivalency
      of these materials is within +/- 1.3%, making them suitable substitutes for
      natural water in both photon and electron beam output measurements over a wide
      energy range. These correction factors are slightly larger than the
      manufacturers' advertised values (+/- 1.0% for solid water and +/- 0.5% for
      virtual water). We suggest that these corrections are large enough in most cases
      and should be applied in the calculation of beam outputs.

PMID- 14684193
TI  - The dosimetry of brachytherapy-induced erectile dysfunction.
AB  - There is emerging evidence that brachytherapy-induced erectile dysfunction (ED)
      is technique-related and may be minimized by careful attention to source
      placement. Herein, we review the relationship between radiation doses to the
      prostate gland/surrounding structures and the development of brachytherapy
      induced ED. The permanent prostate brachytherapy literature was reviewed using
      MEDLINE searches to ensure completeness. Although the site-specific structure
      associated with brachytherapy-induced ED remains unknown, there is an increasing
      body of data implicating the proximal penis. With day 0 CT-based dosimetry, the
      dose to 50% (D50) and 25% (D25) of the bulb of the penis should be maintained
      below 40% and 60% mPD, respectively, while the crura D50 should be maintained
      below 28% mPD to maximize post-brachytherapy potency. To date, there is no data
      to suggest that either radiation doses to the neurovascular bundles or choice of
      isotope is associated with brachytherapy-induced ED, while conflicting data has
      been reported regarding radiation dose to the prostate and the use of
      supplemental external beam radiation therapy. Although the etiology of
      brachytherapy-induced ED is likely multifactorial, the available data supports
      the proximal penis as an important site-specific structure. Refinements in
      implant technique, including preplanning and intraoperative seed placement, will
      result in lower radiation doses to the proximal penis with potential improvement
      in potency preservation.

PMID- 14684194
TI  - The effect of task block arrangement on the detectability of activation in fMRI.
AB  - The effect of task block arrangements on the detection of brain activation was
      investigated. Sessions of functional magnetic resonance imaging (fMRI) including
      the same number of two different task conditions but with different arrangements
      were compared. The two task conditions were, A) Ellipse-shaped black and white
      checkerboard flicker stimulation at 4.2 Hz covering the bilateral visual field,
      and B) the same flicker stimuli covering only the left visual field. In the rest
      blocks (0), the subjects looked at a fixation point. Four different task block
      arrangements were compared, 1) A0 (0A0A0A0) and B0 (0B0B0B0), 2) A0B0
      (0A0B0A0B0A0B0), 3) AB0 (0AB0AB0AB0) and 4) AB (0ABABAB). Bilateral V1, V2, V3
      and the left V5 were activated by condition A, and the right V1 and V2 by B. The
      activation in the left visual field by A0 was larger than in the other three
      conditions. In a differential analysis between conditions A and B, activation in
      the left V3 and V5 was declined by AB0 or AB. When rest blocks were located in
      the post-stimulus undershoot phase, the % signal change of the BOLD signal was
      emphasized, which caused augmented significance in the detection of the activity.
      It was indicated that the outcome of the activation map was influenced by the
      arrangement of task blocks, even though the same number of task blocks were
      repeated within the sessions. In fMRI studies, task conditions should be
      carefully compared within or across sessions considering the characteristics of
      hemodynamic response functions.

PMID- 14684195
TI  - Correlation between nucleus zone migration within scoliotic intervertebral discs
      and mechanical properties distribution within scoliotic vertebrae.
AB  - Correlations between intervertebral disc degeneration and bone mass were
      investigated previously, but never on scoliotic patients. Using MRI measurements
      of intervertebral discs behavior and vertebral bone tomodensitometry,
      correlations between nucleus zone displacement within intervertebral discs and
      mechanical center migration within vertebral bodies were investigated in vivo on
      scoliotic patients. The protocol, performed on eleven scoliotic girls, was
      composed of a CT scan acquisition of apical and adjacent vertebrae followed by a
      MRI acquisition of the thoracolumbar spine. The displacement between the
      vertebral body centroid and inertia center was computed from the CT images and
      called the mechanical migration. The displacement between nucleus zones and
      vertebral body centroids was quantified from MRI and called the nucleus zone
      migration. For apical vertebrae, a significant correlation was found in the
      coronal plane (r = 0.766, p < 0.01), but not in the sagittal plane (r = -0.349, p
      > 0.05). For adjacent vertebrae, significant correlations were found in both
      coronal (r = -0.633, p < 0.05) and sagittal (r = -0.797, p < 0.01) planes. The
      nucleus zone migration occurred in the convexity of the curvature whereas the
      mechanical migration occurred in the concavity.Known secondary mechanical
      phenomenon of scoliosis was quantified using new parameters describing
      intervertebral discs and vertebral bodies. Further investigations should be
      performed to explain the mechanical evolution of scoliosis and to use these
      parameters in predictive criteria of scoliosis.

PMID- 14684196
TI  - Quantification of patellofemoral joint contact area using magnetic resonance
      imaging.
AB  - To describe a method for quantifying patellofemoral joint contact area using
      magnetic resonance imaging (MRI), we used a repeated measures design using
      cadaver specimens. The use of contact area obtained from cadaveric specimens for
      biomechanical modeling does not permit investigators to assess the inter-subject
      variability in contact area as a result of patellofemoral pathology or
      malalignment. Therefore, a method for measuring patellofemoral joint contact area
      in-vivo is necessary. Six fresh frozen unmatched human cadaver knees were thawed
      at room temperature and minimally dissected to permit insertion of a pressure
      sensitive film packet into the suprapatellar pouch. A custom loading apparatus
      was designed to apply a compressive load to the patellofemoral joint at 30
      degrees of flexion. Simultaneous measurement of contact area was made using both
      the pressure sensitive film technique and MRI. The intraclass correlation
      coefficient (ICC) and coefficient of variation were used to compare the agreement
      between the two methods and to assess the repeatability of the MRI method. Good
      agreement was found between the MRI and pressure sensitive film techniques (ICC
      0.91; CV 13%). The MRI technique also was found to be highly reproducible (ICC
      0.98; CV 2.3%). MRI assessment of patellofemoral joint contact area was found to
      be comparable to the established pressure sensitive film technique. These results
      suggest that this method may be a valuable tool in quantifying patellofemoral
      joint contact area in-vivo. Quantification of the patellofemoral joint stress has
      been dependent on patellofemoral joint contact area obtained from cadaver
      specimens, thereby negating the potential influence of subject specific
      variability. Developing a non-invasive technique to evaluate contact area will
      assist researchers and/or clinicians in obtaining patient-specific contact area
      data to be used in biomechanical analyses and clinical decision making.

PMID- 14684197
TI  - A four-element phased array coil for high resolution and parallel MR imaging of
      the knee.
AB  - A four-element phased array coil for MR imaging of the knee was designed, built
      and tested for clinical use at 1.5 Tesla. In routine imaging, it provides over
      twofold increase in signal-to-noise (SNR) compared to two commercially available
      knee coils, and supports higher spatial image resolution. The phased array knee
      coil was also tested for its compatibility with parallel MR imaging that reduces
      imaging time by several folds over conventional MR technique. Results obtained
      using SiMultaneous Acquisition of Spatial Harmonics (SMASH) technique shows that
      our phased array knee coil can be used with parallel MR imaging. These
      improvements may enhance knee diagnosis with higher image quality and reduced
      scan time.

PMID- 14684198
TI  - Simultaneous multiple volume (SMV) acquisition algorithm for real-time navigator
      gating.
AB  - Navigator gating techniques can effectively reduce motion effects in MRI by
      accepting data only when the object is in a small range of positions at the cost
      of significantly prolonging scan time. A simultaneous multiple volume (SMV)
      algorithm is reported here that can substantially increase the scan efficiency
      while maintaining the effectiveness of motion suppression. This is achieved by
      acquiring different image volumes at different motion states. Initial experiments
      demonstrate that SMV can significantly increase the scan efficiency of navigator
      MRI.

PMID- 14684199
TI  - Prediction of total cerebral tissue volumes in normal appearing brain from sub
      sampled segmentation volumes.
AB  - The need for anatomical coverage and multi-spectral information must be balanced
      against examination and processing time to ensure high-quality, feasible imaging
      protocols for clinical research of cerebral development in normal-appearing
      brains. The focus of this study was to create and assess models to estimate total
      cerebral volumes of gray matter, white matter, and cerebrospinal fluid (CSF) from
      anatomically defined sub-samples of full clinical examinations. Pediatric
      patients (18F, 11M; aged 1.7 to 18.7, median 5.2 years) underwent a clinical
      imaging protocol consisting of 3 mm contiguous T1-, T2-, PD-, and FLAIR-weighted
      images after obtaining informed consent. Magnetic resonance imaging (MRI) sets
      were registered, RF-corrected, and then analyzed with a hybrid neural network
      segmentation and classification algorithm to identify normal brain parenchyma.
      The correlation between the image subsets and the total cerebral volumes of gray
      matter, white matter and CSF were examined through linear regression analyses.
      Five sub-sampled sets were defined and assessed in each patient to produce
      estimation models which were all significantly correlated (p < 0.001) with the
      total cerebral volumes of gray matter, white matter, and CSF. Volumes were
      estimated from as little as a single representative slice requiring minimal
      processing time, 27 min, but with an average estimation error of approximately
      6%. Larger sub-samples of approximately three-quarters of the full cerebral
      volume required much more processing time, 2 h and 4 min, but produced estimates
      with an average error less than 2%. This study demonstrated that investigators
      can choose the amount of cerebrum sampled to optimize the acquisition and
      processing time against the degree of accuracy needed in the total cerebral
      volume estimates.

PMID- 14684200
TI  - Three dimensional texture analysis in MRI: a preliminary evaluation in gliomas.
AB  - The discrimination of tumor boundaries from normal tissue, as well as the
      evaluation of tissue heterogeneity and tumor grading often continue to pose a
      challenge in MRI. Although yielding promising results in various fields of
      medical imaging, two- dimensional (2D) texture analysis in MRI has, until now,
      demonstrated a lack of specificity in brain tumor classification. A new three
      dimensional (3D) approach using Cooccurrence Matrix analysis is proposed to
      increase the sensitivity and specificity of brain tumor characterization. A
      preliminary comparative evaluation of 2D and 3D texture analysis was performed on
      T(1)-weighted MRI of seven gliomas for characterization of solid tumor, necrosis,
      edema and surrounding white matter. With 3D compared to 2D method, a better
      discrimination is obtained between necrosis and solid tumor as well as between
      edema and solid tumor. Using both methods, peritumoral white matter overlaps with
      edema, but is completely separated from far homo-lateral matter. This latter
      shows a complete overlapping with contra-lateral matter. The 3D texture analysis
      approach could provide a new tool for tumor grading and treatment follow-up, as
      well as for surgery or radiation therapy planning.

PMID- 14684201
TI  - MRI texture analysis on texture test objects, normal brain and intracranial
      tumors.
AB  - Texture analysis was performed in three different MRI units on T1 and T2-weighted
      MR images from 10 healthy volunteers and 63 patients with histologically
      confirmed intracranial tumors. The goal of this study was a multicenter
      evaluation of the usefulness of this quantitative approach for the
      characterization of healthy and pathologic human brain tissues (white matter,
      gray matter, cerebrospinal fluid, tumors and edema). Each selected brain region
      of interest was characterized with both its mean gray level values and several
      texture parameters. Multivariate statistical analyses were then applied in order
      to discriminate each brain tissue type represented by its own set of texture
      parameters. Texture analysis was previously performed on test objects to evaluate
      the method dependence on acquisition parameters and consequently the interest of
      a multicenter evaluation. Even obtained on different sites with their own
      acquisition routine protocol, MR brain images contain textural features that can
      reveal discriminant factors for tissue classification and image segmentation. It
      can also offer additional information in case of undetermined diagnosis or to
      develop a more accurate tumor grading.

PMID- 14684202
TI  - Changes in MRI signal intensity during hypercapnic challenge under conscious and
      anesthetized conditions.
AB  - Most functional magnetic resonance imaging (fMRI) studies in animals are
      conducted under anesthesia to minimize motion artifacts. However, methods and
      techniques have been developed recently for imaging fully conscious rats.
      Functional MRI studies on conscious animals report enhanced BOLD signal changes
      as compared to the anesthetized condition. In this study, rats were exposed to
      different concentrations of carbon dioxide (CO(2)) while conscious and
      anesthetized to test whether cerebrovascular reactivity may be contributing to
      these enhanced BOLD signal changes. Hypercapnia produced significantly greater
      increases in MRI signal intensity in fully conscious animals (6.7-13.3% changes)
      as when anesthetized with 1% isoflurane (3.2-4.9% changes). In addition, the
      response to hypercapnia was more immediate in the conscious condition (< 30s)
      with signal risetimes twice as fast as in the anesthetized state (60s). Both
      cortical and subcortical brain regions showed a robust, dose- dependent increase
      in MRI signal intensity with hypercapnic challenge while the animals were
      conscious but little or no change when anesthetized. Baseline variations in MRI
      signal were higher while animals were conscious but this was off set by greater
      signal intensity changes leading to a greater contrast-to-noise ratio, 13.1 in
      conscious animals, as compared to 8.0 in the anesthetized condition. In summary,
      cerebral vasculature appears to be more sensitive to hypercapnic challenge in the
      conscious condition resulting in enhanced T2* MRI signal intensity and the
      potential for better BOLD signal changes during functional imaging.

PMID- 14684203
TI  - Gliomatosis cerebri: clinical, neurochemical and neuroradiological response to
      temozolomide administration.
AB  - Gliomatosis cerebri is a rare form of diffusely infiltrating glioma that is
      typically resistant to conventional chemotherapy and radiation therapy and
      carries a poor prognosis. Temozolomide has shown antineoplastic activity against
      malignant gliomas and more recently was beneficial in one patient with
      gliomatosis cerebri. To make an objective assessment of the effect of long-term
      temozolomide administration in a patient with gliomatosis cerebri we used brain
      proton magnetic resonance spectroscopy and structural MRI. A 46-year-old man with
      gliomatosis cerebri was treated with temozolomide (200 mg/m(2) per day for 5 days
      every 28 days). Twenty cycles of temozolomide resulted in a marked reduction in
      choline and scyllo-inositol content, as detected using brain proton MR
      spectroscopy, indicating reduced tumor cellularity and/or growth rate.
      Neurochemical improvements were associated with normalization of the signal
      intensity in most of the previously affected cerebral regions and regression of
      mass effect on MRI. A left pyramidal syndrome, present at the start of the
      treatment, disappeared. Our observation lends support to larger clinical trials
      evaluating the use of temozolomide to treat this brain tumor.

PMID- 14684204
TI  - Water self-diffusion in Chlorella sp. studied by pulse field gradient NMR.
AB  - The water self-diffusion behavior in chlorella water suspension was investigated
      by pulsed field gradient NMR technique. Three types of water was determined,
      which differs according to the self-diffusion coefficients; bulk water,
      extracellular and intracellular water. Intracellular and extracellular water self
      diffusion were restricted, and the sizes of restriction regions were 3.4 microm
      and 17 microm, respectively. The water molecular exchange process between these
      three diffusion regions was investigated. The residence time and exchange rate
      constant for chlorella cells were obtained. The cell wall permeability determined
      from the rate constant as 3 x 10(-6) m/s agreed with the permeability 10(-6) m/s
      obtained from time dependence of intracellular water self-diffusion coefficient.
      The structural cluster model of chlorella cell is estimated to describe the
      extracellular water self-diffusion in chlorella water suspension.

PMID- 14684205
TI  - Magnetic resonance histology: in situ single cell imaging of receptor cells in an
      invertebrate (Lolliguncula brevis, Cephalopoda) sense organ.
AB  - Utilizing contrast-enhanced MR histology, individual cell bodies were identified
      in situ and compared one-to-one with conventional histology. The squid
      Lolliguncula brevis served as a model where the receptor cells of the
      proprioceptive neck receptor organ were labeled with paramagnetic cobalt(II) ions
      by conventional cobalt iontophoresis. Stimulated echo images were obtained using
      a 9.4 T magnet and followed by conventional histologic treatment and light
      microscopy. Images obtained from both these techniques match well and validate MR
      histology.

PMID- 14684206
TI  - A single current density component imaging by MRCDI without subject rotations.
AB  - Magnetic resonance current density imaging (MRCDI) is a useful method for
      measuring electrical current density distribution inside a subject. Due to the
      requirement of subject rotations in MRCDI, MRCDI has not been widely applied to
      in vivo studies. In this paper, we propose a new current density image (CDI)
      reconstruction method by which a single component of the current density can be
      imaged by MRCDI without subject rotations. After measuring one of the two
      magnetic field components, produced by the current density component passing
      through the measurement plane, we have reconstructed the current density
      component images in the spatial frequency domain. Even though the proposed method
      has a limitation that the area of magnetic field measurement should be much
      larger than that of the current density, the proposed method is expected to
      expedite MRCDI applications to in vivo studies.

PMID- 14684207
TI  - Imaging of (13)C-labeled glucose and sorbitol in bovine lens by (1)H-detected
      (13)C nuclear magnetic resonance spectroscopy.
AB  - Bovine lenses were incubated in a solution containing [1-(13)C]glucose (50 mM)
      for 1, 2 and 4 days. Spectroscopic images of [1-(13)C]glucose and [1
      (13)C]sorbitol were constructed using (1)H-detected gradient-enhanced
      heteronuclear multiple-quantum coherence (GE-HMQC) in a 2.0-tesla magnetic field.
      Accumulations of [1-(13)C]glucose and [1-(13)C]sorbitol were mainly observed at
      the periphery of the lens. Their distributions corresponded to the cortex. (1)H
      detected (13)C nuclear magnetic resonance (NMR) spectroscopic imaging by GE-HMQC
      successfully demonstrated the distribution of [1-(13)C]glucose and [1
      (13)C]sorbitol at the periphery of bovine lenses.

PMID- 14684208
TI  - In vivo proton magnetic resonance spectroscopy (MRS) and single photon emission
      computerized tomography (SPECT) in systemic lupus erythematosus (SLE).
AB  - Neuropsychiatric involvement in SLE (NP-SLE) may not be picked up by routine
      neuroimaging procedures like computerized tomography (CT) or magnetic resonance
      imaging (MRI). We prospectively studied the role of single photon emission
      computerized tomography (SPECT) and magnetic resonance spectroscopy (MRS) in
      detection of NP-SLE in 20 patients with lupus (10 with clinical NP involvement
      and 10 without) and 9 healthy controls. MRI abnormalities were seen in 5/10
      patients with NP-SLE while the MRI was normal in all the lupus patients without
      clinical NP involvement. Perfusion defects on SPECT were seen in as many as 8/10
      patients with NP-SLE while only 1/10 lupus patients without clinical NP
      involvement and none of the healthy controls demonstrated perfusion defects. MRS
      revealed abnormal metabolite ratios in all patients with NP-SLE and as many as 8
      lupus patients without clinical NP features. Normal metabolite ratios were
      observed in healthy controls. SPECT and MRS can help detect changes not evident
      on MRI and may serve as useful supplements to existing neuroimaging techniques in
      the diagnosis of NP-SLE. The precise significance of alterations in regional
      cerebral blood flow on SPECT and neurometabolite ratios on MRS needs larger,
      longitudinal studies.

PMID- 14684209
TI  - Another approach to protons with constricted mobility in white matter: pilot
      studies using wideline and high-resolution NMR spectroscopy.
AB  - We report a new approach for the identification of an independent method of
      studying the semi-solid pool of protons, i.e., protons with constrained motion as
      a result of being bound to lipid and protein matrices. These protons cannot be
      observed using conventional imaging techniques since their transverse relaxation
      times are much shorter than the minimum echo times that are currently available
      on clinical scanners. In this pilot study, in vitro multicomponent transverse
      relaxation experiments were made on human white matter slices, fixed in formalin
      (7 normal and 5 with multiple sclerosis). The transverse relaxation decay curves
      were multiexponential and were decomposed to yield three primary components. The
      shortest T(2) component that we obtained (a component too short to be seen by in
      vivo methods) was of the order of microseconds. We hypothesize that this might
      correspond to the macromolecular pool of lipid protons trapped within the myelin
      sheaths. To our knowledge, this is the first attempt at extracting this ultra
      short T(2) component from human white matter. Subsequently, an attempt was made
      to directly detect the lipid protons in a proton NMR spectrum and, if possible,
      measure their concentration in some of the tissues, using the technique of magic
      angle spinning.

PMID- 14684210
TI  - Equivalent cross relaxation rate image for decreasing a false negative case of
      sentinel lymph node biopsy.
AB  - In the breast carcinamas, sentinel lymph node biopsy (SLNB) attracts attention as
      technique to be settled by axillary lymph node metastasis, but existence of a
      false negative case is a problem. Equivalent cross relaxation rate image (ECRI)
      is the measurement method that we can evaluate a change of organization structure
      quantitatively by magnetic resonance imaging. We executed axillary ECRI as a
      purpose with decreasing a false negative case of SLNB. ECRI related to a
      macroscopic image, and it was possible to evaluate yes or no of axillary lymph
      node metastasis. ECRI is the useful method to evaluate adaptability of SLNB.

PMID- 14684211
TI  - Proton MR spectroscopy features of normal appearing white matter in
      neurofibromatosis type 1.
AB  - To determine whether differences exist between neurofibromatosis type 1 (NF1)
      patients with or without focal lesions and healthy normal volunteers in the
      metabolite ratios of normal appearing white matter, 27 patients with NF1 (with
      parenchymal lesion, MR positive, n: 17; without parenchymal lesions, MR negative,
      n: 10) and 20 healthy volunteers underwent MRI and short TE (31 ms) proton MR
      spectroscopy (MRS). In 17 patients with parenchymal lesions, 61 focal lesions
      were detected by MRI. MRS was performed from normal appearing frontal and
      posterior parietal white matter (FWM and PWM) in NF1 and from control groups.
      NAA/Cr, Cho/Cr and MI/Cr ratios were calculated. Significant increase in Cho/Cr
      and MI/Cr ratios were found in FWM and PWM in MR negative and positive groups
      when compared to control group. NAA/Cr ratio in MR positive group was
      significantly decreased in FWM compared to control group. There were no
      significant differences between FWM and PWM in all metabolite ratios of MR
      negative group. MI/Cr ratio in MR positive group was significantly elevated in
      PWM compared to FWM. Metabolite changes detected by MRS could indicate
      demyelination and gliosis in normal appearing white matter in all NF1 patients,
      and additionally neuroaxonal damage in the FWM of NF1 patients with focal
      lesions. For that reason, in the clinical evaluation and follow-up of these
      patients MRS features of normal appearing white matter should be considered in
      addition to focal lesions.

PMID- 14684212
TI  - Straightforward relative quantitation and age-related human standards of N
      acetylaspartate at the centrum semiovale level by CSI (1)H-MRS.
AB  - 1H-MRS was aimed to monitor metabolite concentrations in homogeneous interaxial
      slices of cerebral matter at the centrum semiovale level in healthy volunteers.
      NAA (N-acetylaspartate + N-acetylglutamate), Cr (creatine + phosphocreatine), and
      Cho (choline + acetylcholine) were evaluated by resonance integrations. Using Cr
      as an internal standard, NAA/Cr ratio was considered as a relative measure of
      concentration. CSI sequence explored volunteer's interaxial slices of white and
      gray matter by means of 8 x 8 matrices of (1)H-NMR spectra. NAA/Cr integral
      ratios were averaged over the whole spectral matrix to obtain the Index of NAA at
      Centrum Semiovale (INACS) of each individual. Indexes of the sixty-eight healthy
      volunteers, divided into three groups by age, showed good intraindividual
      reproducibility, and were virtually unaffected by small shifts or bendings of the
      interaxial slice analyzed. The INACSs were used to estimate Age-Sectorial INACS
      Ranges (ASIR), the intervals that, on the basis of a normal statistical
      distribution, should comprise 95% of the age-matched healthy population.
      Individual INACSs, compared to accurately defined ASIRs taken as standards, could
      early detect subtle, diffuse neuronal or axonal damage within centrum semiovale
      interaxial slices. Periodic inspection of INACS could also allow monitoring of
      progressive neuronal or axonal degeneration.

PMID- 14684213
TI  - Monitoring hydrate formation and dissociation in sandstone and bulk with magnetic
      resonance imaging.
AB  - Magnetic resonance imaging (MRI) has been shown to be a very effective tool for
      monitoring the formation and dissociation of hydrates because of the large
      intensity contrast between the images of the liquid components and the solid
      hydrate. Tetrahydrofuran/water hydrate was used because the two liquid components
      are miscible and form hydrate at ambient pressure. These properties made this
      feasibility study proceed much faster than using methane/water, which requires
      high pressure to form the hydrate. The formation and dissociation was monitored
      first in a THF/water-saturated Berea sandstone plug and second in the bulk. In
      both cases it appeared that nucleation was needed to begin the formation process,
      i.e., the presence of surfaces in the sandstone and shaking of the bulk solution.
      Dissociation appeared to be dominated by the rate of thermal energy transfer. The
      dissociation temperature of hydrate formed in the sandstone plug was not
      significantly different from the dissociation temperature in bulk.

PMID- 14684214
TI  - Assessment by MRI of local porosity in dough during proving. theoretical
      considerations and experimental validation using a spin-echo sequence.
AB  - Proving is a key stage in the development of the final structure of bread, as
      invasive measurements may provoke dough collapse. Therefore, better understanding
      and better control of the nucleation and the growth of bubbles require the
      development of non-invasive methods of measurement. In the present work, a non
      invasive method is presented for the measurement of local dough porosity from MR
      image analysis. For this, a direct relation between the gray level of a voxel and
      its gas fraction was established in the absence of heat and mass transfer. At
      whole dough scale for a one-dimensional expansion, the porosity estimated from
      the gray level was compared with the porosity estimated from total dough volume
      measurements in a range of [0.10, 0.74 m(3) of gas/m(3) of dough]. For short
      proving times (<30 min), MR image analysis underestimated porosity by a maximum
      of 0.03 m(3) of gas/m(3) of dough, but otherwise the difference between the two
      means of measurement was within the standard error of total dough measurements
      (+/-0.01 m(3) of gas/m(3) of dough). Maps of local porosity in dough during
      proving are also presented and discussed.

PMID- 14684215
TI  - Venous cavernoma at 8 Tesla MRI.
AB  - Cavernous angiomas or cavernomas are vascular malformations, which may be
      associated with risk of bleeding episodes. We present a case report comparing
      high resolution 8 Tesla gradient echo (GE) imaging with routine fast spin echo
      (FSE) at 1.5 Tesla in a patient with venous cavernoma. A 55-year-old male with a
      history of hemorrhagic stroke was studied using high-resolution 8 Tesla magnetic
      resonance imaging (MRI) system, which revealed venous cavernoma (9 x 8.6 mm) in
      the left parietal region and visualized adjacent microvascular supply. Signal
      loss was prominent in the cavernoma region compared to surrounding brain tissue,
      and signal intensity declined by factor 7.3 +/- 2.4 (679 +/- 62%) on GE images at
      8 Tesla. Cavernoma was not apparent on routine T(2)-weighted FSE images at 1.5
      Tesla MRI. This case report indicates that GE images at 8 Tesla can be useful for
      evaluation of vascular pathologies and microvasculature.

PMID- 14684216
TI  - Primary malignant mesothelioma of the liver: MR imaging findings.
AB  - We report the MR imaging findings of a primary malignant mesothelioma of the
      liver arising from Glisson's capsule. A 54-year-old woman, presenting with acute
      abdominal pain and a large liver mass previously shown on CT, underwent MR
      imaging to characterize the lesion. The tumor was a greater than 12 cm tumor
      located in the right lobe of the liver, which was sharply marginated, with
      heterogeneous internal signal, septations and central necrosis. The tumor was
      considered a hepatocellular carcinoma. The diagnosis of malignant mesothelioma
      was established by immunohistochemical staining and electron microscopy of the
      resected tumor.

PMID- 14684217
TI  - Erroneous and inappropriate use of gamma fits to tracer-dilution curves in
      magnetic resonance imaging and nuclear medicine.

PMID- 14684218
TI  - A delayed class of BOLD waveforms associated with spreading depression in the
      feline cerebral cortex can be detected and characterised using independent
      component analysis (ICA).
AB  - An application of independent component analysis to blood oxygenation level-
      dependent MRI (BOLD-MRI) results was used to detect cerebrovascular changes that
      followed the initiation of cortical spreading depression (CSD) in feline brain.
      The cortical images were obtained from a horizontal plane at 28 s intervals
      before, and for 1.4-1.75 h after, KCl dissolved in agar (KCl/agar) had been
      directly applied to the left suprasylvian gyrus of 13 anesthetized cats for 10
      min. It successfully resolved, for the first time, a novel class of prolonged,
      and delayed, biphasic BOLD waveforms. These were larger in amplitude (
      approximately 20%), longer lasting and more delayed in onset (13-33 min) than the
      brief propagating (90 s) BOLD increase ( approximately 4%) already known to be
      associated with CSD on earlier occasions. Furthermore, such changes occurred in
      localized regions on the hemisphere ipsilateral to the site of stimulus
      application in 4 out of 5 control subjects rather than themselves generating
      propagating waves. Finally, the biphasic waveforms were consistently abolished in
      the 4 experimental animals studied following the i.v. administration of
      sumatriptan (0.3 mg kg(-1)), an antimigraine 5-HT(1B/1D) agonist, 15 min before
      the application of the transient stimulus. They were abolished in 2 out of 4
      animals following the intraperitoneal (i.p.) administration of SB-220453
      (tonabersat: 10 mg kg(-1), 90 min before stimulus application), a novel
      anticonvulsant that has recently been reported to inhibit CSD. ICA has thus been
      successful in detecting a novel localized, as opposed to propagating, signal of
      potential physiological significance hidden in complex BOLD- MRI data, whose
      sensitivity to sumatriptan may relate it to the cerebrovascular changes reported
      in the headache phase of migraine.

PMID- 14684219
TI  - Infections in the surgical patient: an update on trends and treatment.
      Introduction.

PMID- 14684220
TI  - Hospital-acquired and ventilator-associated pneumonia: what's new in diagnosis
      and treatment?

PMID- 14684221
TI  - The continuing challenge of intra-abdominal infection.
AB  - Intra-abdominal infection is common and frequently seen by the surgeon. Mortality
      is related to disease acuity and organ failure. This report, based on medical
      literature and personal experience, is a brief review of this subject,
      highlighting important historical milestones and recent advances in surgical and
      antibiotic therapy. Peritonitis remains a clinical challenge. Aggressive
      resuscitation, diagnostic imaging, and surgical treatment are the mainstays of
      appropriate therapy. Percutaneous drainage of intra-abdominal collections has
      increased over time and is particularly helpful in certain postoperative
      patients. Adjunctive antibiotic therapy against gram-negative aerobes and
      anaerobes should be limited to a 7- to 10-day course, except in selected
      patients, such as those with inadequate source controls.

PMID- 14684222
TI  - State-of-the-art therapy for severe sepsis and multisystem organ dysfunction.
AB  - Despite spectacular advances in life-support technology, the management of
      patients with severe sepsis continues to be a significant health care challenge
      because of the associated major morbidity, high mortality, and health economic
      implications. Severe sepsis with associated multisystem organ dysfunction (MOD)
      is the leading cause of death in the intensive care unit. Recent understanding of
      the pathophysiology now demonstrates that the syndrome of severe sepsis after a
      major physiologic insult is characterized by the activation of multiple
      overlapping and interacting cascades leading to systemic inflammation, a
      procoagulant state, and decreased fibrinolysis, which if unchecked leads to the
      progressive functional deterioration of multiple interdependent organs. This
      review will highlight the epidemiology, current understanding of the
      pathophysiology, management, and prevention of the syndrome of severe sepsis with
      MOD.

PMID- 14684224
TI  - Skin and soft-tissue infections: impact of resistant gram-positive bacteria.
AB  - Surgical site infections remain significant causes of postoperative morbidity and
      mortality despite an improved understanding of risk factors and an increasing
      armamentarium of antimicrobial agents. The overall rates of surgical site
      infections have been slowly decreasing, but the proportion of infections with
      gram-positive bacteria continues to increase, and drug-resistant species continue
      to become more prevalent. Although new antibiotic classes have efficacy against
      such organisms, these agents are only short-term solutions to the problem of
      multiple-drug resistance. Surgeons must focus on prevention of infections by
      appropriately using antibiotics, emphasizing principles of infection control, and
      understanding nontraditional measures that may decrease infection risk.

PMID- 14684226
TI  - An evidence-based approach to diabetic foot infections.
AB  - Foot infections are a major complication of diabetes mellitus and contribute to
      the development of gangrene and lower extremity amputation. Recent evidence
      indicates that persons with diabetes are at greater risk for infection because of
      underlying neuropathy, peripheral vascular disease, and impaired responses to
      infecting organisms. This article reviews the underlying pathophysiology, causes,
      microbiology, and current management concepts for this potentially limb
      threatening complication. Multidisciplinary management consisting of teams of
      specialists with a focus on limb preservation can make significant improvements
      in outcomes, including a reduction in rates of lower extremity amputation.

PMID- 14684227
TI  - The driving force in hospital formularies: economics versus efficacy.
AB  - The rising cost of pharmaceuticals has created a focus on hospital cost
      containment. From 1990 to 2000, spending on prescription drugs increased 200%.
      Through a variety of mechanisms and contracting, hospital formularies have become
      increasingly more restrictive. Physician choice with regard to antibiotics
      specifically is becoming more limited. The field of pharmacoeconomics looks at
      the cost effectiveness of the drugs we use. The pressures on the pharmaceutical
      industry and hospitals are reviewed here with a discussion of antibiotic
      prophylaxis, new expensive therapies, and physician responsibility. The driving
      force behind hospital formulary design is often economic, whereas the physician
      desires variety and efficacy. This review discusses some of the key issues
      related to drug costs and expenditures.

PMID- 14684230
TI  - The supportive academic environment: ingredients for success.
AB  - Despite the many dire pronouncements of the moribund status of the academic
      triple threat, this species is far from extinct. Maintenance and, indeed,
      expansion of this pool of individuals requires their identification and support
      early in their careers, and nurturing and mentoring throughout their careers.
      Increasing demands for clinical service and revenue generation make it all the
      more critical that institutions and their faculty and administrative personnel in
      leadership positions support these increasingly rare academicians and that the
      individuals themselves develop and maintain diligence, superlative organizational
      skills, the ability to prioritize and the flexibility to reprioritize,
      perseverance, and above all, a sense of humor. Early in career development,
      perhaps the most important element in this equation is the mentor. The present
      article is in large measure a tribute to the mentoring role played by Dr. Michael
      J. Painter in the careers of his residents, fellows, and faculty throughout more
      than two decades as Chief of the Division of Child Neurology at the University of
      Pittsburgh School of Medicine and Children's Hospital of Pittsburgh.

PMID- 14684231
TI  - Contribution of child neurology to the investigation and care of children with
      developmental disorders.

PMID- 14684232
TI  - Phenytoin and phenobarbital stable isotope studies in neonates.
AB  - A pharmacokinetic study of phenytoin and phenobarbital with nonradioactive
      isotopes was performed in nine neonates in an intensive care unit setting. A
      single-pulse dose of either labeled phenobarbital (1,3-(15)N, 2-(13)C) or labeled
      phenytoin (2-(13)C, 1, 3-(15)N) was administered to neonates who manifested
      gestation between 25 and 40 weeks and were receiving maintenance medication.
      Blood samples were collected at fixed intervals, and with a computerized gas
      chromatography mass spectrometry system, plasma concentrations of the labeled and
      unlabeled drug in relation to time administered were obtained. According to the
      calculations obtained from labeled analogue, several kinetic characteristics
      related to drug absorption, clearance, and elimination were determined. The use
      of a nonradioactive labeled isotope overcomes the limitations of conventional
      pharmacokinetic methodology and can be specifically useful in neonates and
      infants in whom volumes of distribution are rapidly changing and steady state is
      not achieved.

PMID- 14684233
TI  - Neonatal seizures and brain damage.
AB  - There are four unresolved clinical issues at bedside with respect to the
      recognition, differential diagnosis, prognosis, and treatment of infants who
      present with seizures. There is also an overriding fifth question which bridges
      these four clinical issues, based on a laboratory researcher's perspective at the
      "bench". Given the increasing understanding of the neurobiologic and
      pathophysiologic explanations for seizures in animal models, one must consider
      the question of whether neonatal seizures cause brain injury or are a surrogate
      of injury resulting from other etiologies.

PMID- 14684234
TI  - The status of hematopoietic stem cell transplantation in lysosomal storage
      disease.
AB  - Lysosomal storage diseases are a group of disorders which have in common an
      inherited defect in lysosomal function-in most cases, a missing intralysosomal
      enzyme. Research into potential treatment options for this group of disorders has
      focused on enzyme replacement. Over the past two decades, hematopoietic stem cell
      transplantation has been used with increasing frequency to treat patients with
      lysosomal storage disease by providing a population of cells with the capacity to
      produce the missing enzyme. The success of marrow transplantation depends on the
      specific enzyme deficiency and the stage of the disease. Generally, visceral
      symptoms can be improved, whereas skeletal lesions remain relatively unaffected.
      The effect on neurologic symptoms varies. Hematopoietic stem cell transplantation
      remains a viable treatment option in those lysosomal storage diseases where data
      supportive of disease stabilization or amelioration are known. Early
      transplantation is the goal so that enzyme replacement may occur before extensive
      central nervous system injury becomes evident. When inadequate clinical data are
      available, the decision to perform transplantation requires experimental data
      demonstrating that the enzyme in question is both excreted from normal cells and
      taken up by affected cells as evidenced by elimination of storage material in
      vitro.

PMID- 14684235
TI  - Tuberous sclerosis complex: genetics to pathogenesis.
AB  - Desiree-Magloire Bourneville first reported tuberous sclerosis complex as
      "tuberous sclerosis of the cerebral convolutions" in 1880. This disorder is
      characterized by multiple hamartomas in several organs, particularly the brain.
      Commonly recognized clinical features include hypomelanotic skin macules, facial
      angiofibromas, periungual fibromas, delayed development, and seizures.
      Abnormalities on brain imaging include subependymal nodules, cortical tubers, and
      radial white matter lines. The kidney, heart, and retina are among other commonly
      affected organs. Although the majority of cases (65%) are sporadic, genetic
      linkage studies of familial cases led to the discovery of two separate genes
      linked to tuberous sclerosis complex: TSC1, located at chromosome 9q34, encoding
      a protein called hamartin; and TSC2, located at chromosome 16p13.3, encoding a
      protein called tuberin. Tuberin has a region of homology to rap1GAP, a guanosine
      triphosphatase-activating protein. This observation is consistent with the idea
      of tuberin functioning in a cellular signaling pathway. Hamartin contains a
      single potential transmembrane domain; orthologues in yeast, drosophila, and rat
      have been cloned. Hamartin also binds to ezrin and other ezrin-radixin-moesin
      proteins, which link the cell membrane to the cytoskeleton. Tuberin and hamartin
      interact directly with each other, and the complex may function together to
      regulate specific cellular processes. This study reviews current ideas regarding
      the function of tuberin and hamartin, and the pathogenesis of tuberous sclerosis
      complex.

PMID- 14684236
TI  - Bilirubin toxicity in the developing nervous system.
AB  - Bilirubin toxicity remains a significant problem despite recent advances in the
      care of jaundiced (hyperbilirubinemic) neonates. A recent surge in reported cases
      of classical kernicterus, due in part to earlier hospital discharge and
      relaxation of treatment criteria for hyperbilirubinemia, and new reports of
      hyperbilirubinemia-induced auditory dysfunction using evoked potential based
      infant testing and hearing screening, underscore the need to better understand
      how hyperbilirubinemia causes brain damage in some infants, especially because
      the damage is preventable. Recent progress in understanding bilirubin binding and
      neurotoxicity resulting from unbound or "free" unconjugated bilirubin, how
      bilirubin affects the central nervous system in vivo and in vitro, and the use of
      new clinical tools in neonates, for example magnetic resonance imaging revealing
      bilateral lesions in globus pallidus and subthalamus, and abnormal brainstem
      auditory evoked potentials with normal inner ear function, may lead to improved
      detection and prevention of neurologic dysfunction and damage from bilirubin.
      Finally, the concern is raised that partial or isolated neurologic sequelae, for
      example auditory neuropathy and other central auditory processing disorders, may
      result from excessive amount and duration of exposure to free, unconjugated
      bilirubin at different stages of neurodevelopment.

PMID- 14684237
TI  - Relapsing-remitting, corticosteroid-sensitive, varicella zoster virus optic
      neuritis.
AB  - We report a 13-year-old male who presented with bilateral disc edema after a
      febrile illness. Rapid loss of vision prompted corticosteroids treatment, which
      reversed the visual loss and optic disc findings. Both his visual function and
      disc edema proved exceedingly sensitive to steroids, and he required increasingly
      slow and prolonged corticosteroids taper to avoid relapse over a period of 1
      year. Ultimately, profound visual loss was reversed three times and only after
      exceptionally slow steroid weaning. Comprehensive systemic investigations and
      neuroimaging were initially unrevealing. Late in the course of disease, evidence
      of seroconversion was identified in his serum and cerebrospinal fluid with
      positive varicella zoster virus antibodies titers. Varicella zoster virus-related
      optic nerve pathology may present clinically with profound visual loss and disc
      edema and may reverse only with high-dose corticosteroids treatment. Physicians
      should carefully consider retesting with late varicella zoster virus titer in
      patients with relapsing-remitting, steroid-sensitive optic neuritides.

PMID- 14684238
TI  - Triptans for treatment of acute pediatric migraine: a systematic literature
      review.
AB  - The purpose of this article is to evaluate the effectiveness and safety of
      triptans for the treatment of acute migraine in children and adolescents.
      Randomized and open label trials of triptans in acute pediatric patients (ages 6
      18 years) were identified by Medline (1966-2002) and PubMed (1991-2002).
      Additional reports were identified from the reference list of the retrieved
      studies. To study effectiveness, only randomized controlled trials were included,
      but open label studies were also included to study adverse effects.
      Pharmacokinetic studies of triptans in pediatric patients were also searched.
      Four randomized controlled trials were identified. One study reported oral
      sumatriptan, another oral rizatriptan, and two studies reported nasal spray
      sumatriptan. Rizatriptan is well tolerated but not clearly beneficial when used
      in adolescents. Effectiveness of nasal spray sumatriptan in acute pediatric
      migraine where other medications had failed was supported. Effectiveness of oral
      sumatriptan was not established. Adverse effects were minor for oral sumatriptan
      and rizatriptan and nasal sumatriptan. Pharmacokinetics of sumatriptan in
      pediatric patients has not been established. In conclusion, nasal spray
      sumatriptan should be considered in acute pediatric migraine in patients not
      experiencing adequate relief with other interventions.

PMID- 14684239
TI  - Supratentorial primitive neuroectodermal tumors of infancy: clinical and
      radiologic findings.
AB  - One hundred ninety-eight children were entered on POG 8633, "Prolonged
      Postoperative Chemotherapy and Delayed Radiation for Children <3 years of age
      with Malignant Brain Tumors" (1986-1990). Thirteen manifested supratentorial
      nonpineoblastoma primitive neuroectodermal tumors, making this the second most
      common supratentorial tumor in the study. Symptoms and signs included seizures,
      nausea, vomiting, lethargy, irritability, headache, focal motor weakness, and
      increased head circumference. Twelve of 13 had symptoms for less than 1 month
      before diagnosis. The average tumor size was 5.96 cm (+/- 0.37) x 5 cm (+/- 0.28)
      x 5.15 cm (+/- 0.31). Eight tumors were predominantly hemispheral, and five were
      midline. Computed tomographic scans on nine patients revealed tumor hyperdensity
      (nine), midline shift (eight), hydrocephalus (seven), cysts (six), well-defined
      borders (five), and calcification (four). No patients exhibited peritumoral
      edema. Contrast enhancement, primarily heterogeneous, was present in all
      patients. Magnetic resonance imaging appearance of the tumor (six patients)
      demonstrated midline shift (four), well-defined margins (four), necrosis (two),
      cysts (three), and hemorrhage (two). No peritumoral edema was present. Most
      enhanced heterogeneously. The diagnosis of supratentorial nonpineoblastoma
      primitive neuroectodermal tumors should be suspected when a large, sharply
      marginated, hyperdense supratentorial mass is observed in a young child,
      particularly when no peritumoral edema is present.

PMID- 14684240
TI  - Quantitative follow-up analysis by computed tomographic imaging in neonatal
      hydrocephalus.
AB  - We sought a simple and accurate method to monitor neonatal hydrocephalic infants
      using standard computed tomographic scans. Volume measurements were made by means
      of pixel counting using a personal computer and a drawing device, as a graphic
      tablet system, over computed tomographic scans of six infants with neonatal
      hydrocephalus and four age-matched control infants. The mean value (763.9 +/-
      83.3 cm(3)) of the volume of the cranium in the hydrocephalic group was two times
      higher than that in the age-matched control infants (360.4 +/- 41.4 cm(3)), P <
      0.00001. Sequential changes of the ventricular/intracranial volume ratio steadily
      decreased after cerebrospinal fluid diversion by means of a "two-step procedure"
      as early in postnatal life as feasible. The mean value (0.67 +/- 0.12) of the
      lateral ventricle/intracranial volume ratio at birth improved to 12 months of age
      (0.26 +/- 0.14), P < 0.05. This study has documented, by means of quantitative
      analysis of serial scans, a statistically significant increase in the neonatal
      hydrocephalic brain volume after cerebrospinal fluid shunting.

PMID- 14684241
TI  - Hypoalbuminemia with valproic acid administration.
AB  - Valproic acid and its derivatives are commonly administered antiepileptic drugs
      for children and adults. Five residents at a children's long-term care facility
      manifested hypoalbuminemia while being administered divalproex, although serum
      liver function test results and urinalysis results were normal. When the patients
      were free from valproic acid, the serum albumin levels increased into the normal
      range (17-30% higher than the serum albumin levels while patients were receiving
      valproic acid) despite the absence of any dietary changes. Comparing the serum
      albumin levels for eight residents who received divalproex (3.1 gm/dL +/- 0.4
      gm/dL) with the serum albumin levels for 13 residents who were not receiving
      valproic acid or its derivatives (3.8 gm/dL +/- 0.2 gm/dL), the difference was
      significant (P < 0.001). This difference could not be accounted for by
      nutritional, environmental, laboratory, or urinary causes. In this study,
      divalproex administration was a contributing factor in the development of
      reversible hypoalbuminemia in this population of severely disabled,
      neurologically injured children and young adults. Further studies are required to
      determine the exact etiology and clinical significance of valproate-mediated
      hypoalbuminemia.

PMID- 14684242
TI  - Alpha-lactalbumin-enriched diets enhance serotonin release and induce anxiolytic
      and rewarding effects in the rat.
AB  - Among food proteins, alpha-lactalbumin (LAC) has the highest ratio of tryptophan
      (Trp) over its competitor amino acids. Consequently, contrary to casein (CAS),
      LAC ingestion increases Trp access to the brain leading to enhanced serotonin (5
      HT) synthesis. As an index of serotonergic activity, we assessed extracellular 5
      HT in response to LAC ingestion, using microdialysis, and performed behavioural
      tests in rats in order to characterise the suggested improvements of mood
      observed in humans after ingestion of this protein. Rats were fed with diets
      enriched either in LAC or CAS as control, acutely (30 min meals) or chronically
      (3 and 6 days). A 30 min LAC meal significantly increased 5-HT release in the
      medial hypothalamus. This effect disappeared after 3 and 6 days of diet. The
      basal premeal 5-HT levels were increasingly enhanced by the LAC diet. Compared to
      a CAS meal, LAC increased the percentage of time spent on the open arms of the
      elevated plus maze and the number of visits to the centre of the open field,
      suggesting an anxiolytic-like effect. A single LAC meal decreased sucrose
      consumption, while 3 or 6 days diets enhanced it, reflecting an appetitive and/or
      rewarding action. In conclusion, LAC ingestion induces anxiolytic-like and
      rewarding effects possibly related to serotonergic activation. Shifting
      transiently, the commonly consumed CAS-enriched to LAC-enriched diets may induce
      beneficial effects on mood.

PMID- 14684243
TI  - Comparing immune activation (lipopolysaccharide) and toxin (lithium chloride)
      induced gustatory conditioning: lipopolysaccharide produces conditioned taste
      avoidance but not aversion.
AB  - Feeding and drinking typically involve both appetitive and consummatory
      behaviors. Appetitive behaviors include those behaviors produced by an animal
      prior to the actual consumption, such as approach movements, whereas consummatory
      behaviors (such as licking and chewing) are involved in the actual consumption of
      food. The present research compared the gustatory conditioning effects of
      bacterial lipopolysaccharide (LPS) and lithium chloride (LiCl) in two different
      paradigms, conditioned taste avoidance and conditioned taste aversion which
      differentially affect the appetitive and consummatory components of feeding. Male
      rats were implanted with intraoral cannulae and habituated to a water deprivation
      schedule and afterwards received two conditioning days (Days 1 and 4). Each
      conditioning day consisted of 1 h access to a novel sucrose solution (0.3 M)
      immediately followed by a systemic injection of LPS (200 microg/kg), LiCl (0.15
      M, 3 meq) or NaCl vehicle. Conditioned taste aversion was assessed using the
      taste reactivity test on Day 7, where orofacial and somatic responses were
      videotaped and analyzed during 3 brief (1 min) exposures to the sucrose solution.
      Conditioned taste avoidance was assessed on Days 8 and 9 using a two-bottle
      preference test (sucrose versus water). Animals conditioned with LiCl displayed
      typical aversive-like responses in the taste reactivity paradigm evidenced by
      significant reductions in positive ingestive responses (P<0.05) and an increase
      in active aversive responses (P<0.05) relative to controls. Furthermore, LiCl
      treatment resulted in conditioned avoidance of sucrose in the two-bottle
      preference test characterized by a decreased sucrose preference (P<0.05).
      Conditioning with LPS produced a reduced sucrose preference (P<0.05) relative to
      controls, comparable to the avoidance seen in LiCl-treated rats. In contrast,
      conditioning with LPS resulted in similar positive ingestive responses to
      intraorally infused sucrose as seen in controls. The present results demonstrate
      that LPS treatment produces conditioned avoidance but not aversion and suggest
      that LPS can selectively condition the appetitive aspects of feeding whereas the
      consummatory behaviors remain unaffected.

PMID- 14684244
TI  - Effects of hippocampal lesions in a food location task in pigeons.
AB  - This study investigated the role of the hippocampus in pigeons learning of a food
      related choice task. The effects of lesions induced by ibotenic acid were
      analyzed in two experiments. Experiment 1 investigated the effects of hippocampal
      damage on postoperative memory retrieval and in reversal learning. Experiment 2
      investigated the effects of hippocampal lesions on the acquisition and reversal
      of learning. In both experiments probe tests were used to assess the behavioral
      strategies underlying the choice. In Experiment 1 hippocampal lesions impaired
      the preoperative learned performance in terms of choice latency but not choice
      accuracy. Experiment 2 data showed that, in postoperative learning sessions,
      latency as well as choice accuracy were impaired by hippocampal damage. The probe
      tests, in which a curtain was placed around the chamber, revealed behavioral
      patterns of a non-mapping strategy. This was true in both experiments and groups
      (experimental and controls). Immediately after training, during the probe tests
      of both experiments, in which food cups were omitted, the three groups spent more
      time in the target quadrant. However, immediately after the reversal condition,
      neither hippocampal damaged nor control pigeons showed a preference for the
      target quadrant. This may be interpreted as evidence for a hippocampal role in
      stimulus location learning involving non-mapping strategies.

PMID- 14684245
TI  - Some characteristics of tactile channels.
AB  - The four information-processing channels of glabrous skin have distinct tuning
      characteristics which appear to be determined in the periphery at the level of
      sensory receptors and their afferent nerve fibers. The four-channel model [J
      Acoust Soc Am 84 (1988) 1680] has been updated to include measurement over a
      wider frequency range of tuning of the P and NP I channels, psychophysically
      determined by forward-masking and adaptation tuning curve methods. In addition to
      differences in their tuning, the P and NP channels differ in the following ways:
      (1) the P channel, but not NP channels, has been found to be capable of temporal
      summation, which operates by neural integration; (2) the capacity for spatial
      summation is also an exclusive property of the P channel; (3) sensitivity
      declines with age at a greater rate in the P channel than in the NP channels; (4)
      the masking or adaptation of a channel has no effect on the sensitivity of the
      other channels, although the channels interact in the summation of the perceived
      magnitudes of stimuli presented to separate channels.

PMID- 14684246
TI  - Passive, active and intra-active (self) touch.
AB  - A series of experiments are described in which magnitude estimates of the
      perceived size of steel balls were made when the balls were actively rolled
      between the fingertip and several other body sites (thumb, thenar eminence,
      forearm). This movement, called scripting, involves actively moving an object by
      a touching surface over another surface of the body which is passively being
      touched. We define this active/passive activity as "intra-active touch" and the
      results show that the perceptual size of the balls is dependent upon the body
      part passively being activated. An additional series of experiments decoupled the
      actively generated and passively received tactile information by having subjects
      either perform the scripting on another individual's body site or by having the
      other individual roll the balls on the subject's various sites. The latter
      experiments showed that the passive body can contribute to the overall impression
      of the size of the balls, but only when the intra-active touching involved the
      glabrous skin of the hands. Intra-active touch between the active finger and the
      passively touched hairy skin of the forearm showed no effect of the touched
      surface on the perceived size of the balls. The results suggest that the
      mechanisms of intra-active touch are different when glabrous skin activates
      glabrous skin than when glabrous skin activates hairy skin.

PMID- 14684247
TI  - The adenosine A2A antagonist KF17837 reverses the locomotor suppression and
      tremulous jaw movements induced by haloperidol in rats: possible relevance to
      parkinsonism.
AB  - Recent evidence indicates that adenosine A2A receptors modulate the activity of
      striatal neurons, and that antagonists of this receptor may have actions in
      various animal models related to motor function. Four experiments were conducted
      to study the effects of systemic injections of the adenosine A2A antagonist
      KF17837 on the behavioral effects produced by repeated administration of the
      dopamine (DA) antagonist haloperidol. In the first two experiments, it was shown
      that repeated 0.5 mg/kg haloperidol severely suppressed open-field locomotor
      activity, and that KF17837 (0.0-20.0 mg/kg) did not significantly increase open
      field locomotor activity. The third experiment demonstrated that injections of
      KF17837 (0.0-20.0 mg/kg) completely reversed the suppression of locomotion
      induced by haloperidol, and also increased rearing behavior in haloperidol
      treated rats. Previous research has reported that haloperidol induces tremulous
      jaw movements that have many of the characteristics of parkinsonian tremor. The
      fourth experiment demonstrated that i.p. injections of KF17837 (0.0-20.0 mg/kg)
      also suppressed haloperidol-induced tremulous jaw movements. Taken together, the
      results of these experiments indicate that adenosine A2A antagonism can reverse
      the locomotor suppression and tremulous movements induced by DA antagonism. This
      profile of activity is consistent with the hypothesis that antagonism of
      adenosine A2A receptors can result in an antiparkinsonian effect in animal
      models.

PMID- 14684248
TI  - Pretraining or previous non-spatial experience improves spatial learning in the
      Morris water maze of nucleus basalis lesioned rats.
AB  - Previous experiments have shown that infusions of ibotenic acid in the nucleus
      basalis magnocellularis (NBM) induce a strong impairment in spatial navigation
      for a hidden platform in the Morris water maze. This effect was initially
      attributed to a cholinergic deficit, but later studies showed that performance
      level did not correlate with the degree of cholinergic denervation. Therefore,
      this impairment is due to a combined cholinergic and non-cholinergic deficit.
      However, it is not clear in which particular processes the NBM is involved. In
      this study we have evaluated the origin of behavioural impairment in spatial
      navigation in the water maze after an ibotenic acid-induced lesion of NBM. In the
      first experiment, Wistar rats were trained preoperatively in an allocentric
      navigation task. Postoperatively, they were tested in the same task. All lesioned
      animals showed a performance level similar to controls. Lesions did not impede
      the acquisition of new positions in the water maze, nor did affect the ability of
      animals to remember new platform positions after an intertrial interval of 20s,
      even if animals had received only allocentric experience with the platform
      position, or allocentric and path integration information concurrently. Lesions
      also failed to affect the ability to locate a hidden platform in a new
      environment. However, hippocampal infusions of scopolamine (5 microg) produced a
      severe impairment in NBM-damaged animals, without impairing performance of
      controls. In the second experiment Wistar rats with the same lesion were first
      trained in a visual-guided task in the water maze, and subsequently evaluated in
      the spatial task. In both tasks lesioned animals were not different from
      controls. These results suggest that the NBM played an important role during
      acquisition phases but not in the execution of spatial navigation. Moreover, the
      excessive emotional response displayed by lesioned animals is postulated as a
      relevant cause for the impairment observed in spatial navigation after NBM
      damage.

PMID- 14684249
TI  - The role of dopamine in learning, memory, and performance of a water escape task.
AB  - Dopamine-deficient (DD) mice have selective inactivation of the tyrosine
      hydroxylase gene in dopaminergic neurons, and they die of starvation and
      dehydration at 3-4 weeks of age. Daily injections of L-DOPA (50 mg/kg, i.p.)
      starting approximately 2 weeks after birth allow these animals to eat and drink
      enough for survival and growth. They are hyperactive for 6-9 h after receiving L
      DOPA and become hypoactive thereafter. Because these animals can be tested in the
      presence or absence of DA, they were used to determine whether DA is necessary
      for learning to occur. DD mice were tested for learning to swim to an escape
      platform in a straight alley in the presence (30 min after an L-DOPA injection)
      or absence (22-24 h after an L-DOPA injection) of dopamine. The groups were split
      24 h later and retested 30 min or 22-24 h after their last L-DOPA injection. In
      the initial test, DD mice without dopamine showed no evidence of learning,
      whereas those with dopamine had a learning curve similar in slope to controls but
      significantly slower. A retest after 24 h showed that DD mice can learn and
      remember in the absence of dopamine, leading to the inference that the lack of
      dopamine results in a performance/motivational decrement that masks their
      learning competence for this relatively simple task.

PMID- 14684250
TI  - Impaired object recognition with increasing levels of feature ambiguity in rats
      with perirhinal cortex lesions.
AB  - It has been proposed that the perirhinal cortex is involved in the representation
      of the characteristics of objects. In particular it has been proposed that it is
      critical for discriminating between stimuli which have some features in common
      and thus it has been described as being involved in resolving feature ambiguity.
      The present experiments demonstrate that lesions of perirhinal cortex in the rat
      cause impairments in object recognition which increase with the level of feature
      ambiguity present in the discrimination. Although increasing feature ambiguity
      increases the overall difficulty of discriminations, lesions of the perirhinal
      cortex resulted in a disproportionate impairment when feature ambiguity was
      increased and not when the difficulty of the discrimination was increased through
      enlargement of the stimulus set. The present experiments therefore support the
      view that perirhinal cortex in the rat is critical to resolution of feature
      ambiguity in stimulus specification.

PMID- 14684251
TI  - Age-related vulnerability to diencephalic amnesia produced by thiamine
      deficiency: the role of time of insult.
AB  - Age is a risk factor for the development of many neurological disorders,
      including alcohol-related neurological disorders. A rodent model of Wernicke
      Korsakoff Syndrome (WKS), acute pyrithiamine-induced thiamine deficiency (PTD),
      produces diencephalic damage and impairments of memory similar to what is seen in
      WKS patients. Advanced age increases the vulnerability to the cascade of acute
      and some chronic neurological events caused by PTD treatment. Interactions
      between PTD treatment and age at the time of treatment (3, 10, or 21 months), in
      addition to the effects of an increased recovery period, were examined relative
      to spatial memory impairment and neuropathology in Fischer 344 rats. Although
      acute neurological disturbances and medial thalamic brain lesions were more
      prevalent in middle-aged and senescent rats exposed to PTD treatment, relative to
      young rats, behavioral data did not support the view that PTD and aging have
      synergistic effects. In addition, both advanced age and PTD treatment result in a
      loss of basal forebrain cholinergic neurons, though there was no interaction.
      Despite the fact that no convincing evidence was found for an effect of extended
      recovery time on neuropathology measures, young rats given an extensive recovery
      period displayed less working memory impairment. In summary, these data provide
      evidence for an increased susceptibility of the aged rat to the acute
      neurological consequences and diencephalic pathology associated with PTD
      treatment and indicated a similar vulnerability of the middle-aged rat. However,
      the synergistic interaction between aging and PTD treatment in thalamic tissue
      loss did not express behaviorally.

PMID- 14684252
TI  - Environmental enrichment enhances sensitization to GBR 12935-induced activity and
      decreases dopamine transporter function in the medial prefrontal cortex.
AB  - Rats raised in an enriched condition (EC) during development display increased
      hyperactivity to the effect of acute amphetamine compared to rats raised in an
      impoverished condition (IC). The present study determined whether environmental
      enrichment differentially alters the effects of GBR 12935 administration, a
      selective dopamine transporter (DAT) inhibitor. Acutely, EC rats showed a
      greater, dose-dependent GBR 12935-induced increase in activity compared to IC
      rats; however, basal activity for EC rats was lower than for IC rats. After
      repeated GBR 12935, only EC rats exhibited behavioral sensitization. Kinetic
      analysis of DAT function in medial prefrontal cortex (mPFC) revealed that the
      maximal velocity of [3H]dopamine ([3H]DA) uptake in EC rats was less than in IC
      rats (4.9 +/- 0.6 and 7.7 +/- 0.6 pmol/min/mg, respectively), but not in striatum
      or nucleus accumbens. Furthermore, GBR 12935-induced inhibition of DAT function,
      [3H]GBR 12935 binding density and DA content in mPFC, striatum and nucleus
      accumbens were not different between EC and IC rats. However,
      dihydroxyphenylacetic acid content in mPFC was lower in EC than IC rats, whereas
      no differences were found in striatum and nucleus accumbens. These results
      suggest that EC-induced changes in activity may be due to decreased DAT function
      and decreased DA metabolism in the mPFC.

PMID- 14684253
TI  - Use of the elevated T-maze to study anxiety in mice.
AB  - We have recently suggested that the elevated T-maze (ETM) is not a useful test to
      study different types of anxiety in mice if a procedure similar to that
      originally validated for rats is employed. The present study investigated whether
      procedural (five exposures in the enclosed arm instead of three as originally
      described for rats) and structural (transparent walls instead of opaque walls)
      changes to the ETM leads to consistent inhibitory avoidance acquisition (IAA) and
      low escape latencies in mice. Results showed that five exposures to the ETM
      provoked consistent IAA, an effect that was independent of the ETM used. However,
      the ETM with transparent walls (ETMt) seemed to be more suitable for the study of
      conditioned anxiety (i.e. IAA) and unconditioned fear (escape) in mice, since IAA
      (low baseline latency with a gradual increase over subsequent exposures) and
      escape (low latency) profiles rendered it sensitive to the effects of anxiolytic
      and anxiogenic drugs. In addition to evaluation of drug effects on IAA and
      escape, the number of line crossings in the apparatus were used to control for
      locomotor changes. Results showed that whereas diazepam (1.0-2.0 mg/kg) and
      flumazenil (10-30 mg/kg) impaired IAA, FG 7142 (10-30 mg/kg) did not provoke any
      behavioral change. Significantly, none of these benzodiazepine (BDZ) receptor
      ligands modified escape latencies. The 5-HT1A partial receptor agonist buspirone
      (1.0-2.0 mg/kg) and the 5-HT releaser fenfluramine (0.15-0.30 mg/kg) impaired IAA
      and facilitated escape, while the full 5-HT1A receptor agonist, 8-OH-DPAT (0.05
      0.1 mg/kg) and the 5-HT(2B/2C) receptor antagonist, SER 082 (0.5-2.0 mg/kg)
      failed to modify either response. mCPP (0.5-2.0 mg/kg), a 5-HT(2B/2C) receptor
      agonist, facilitated IAA but did not alter escape latency. Neither antidepressant
      utilized in the current study, imipramine (1.0-5.0 mg/kg) and moclobemide (3.0-10
      mg/kg) affected IAA or escape performance in mice. The well-known anxiogenic
      drugs yohimbine (2.0-8.0 mg/kg) and caffeine (10-30 mg/kg) did not selectively
      affect IAA, although caffeine did impair escape latencies. Present results
      suggest the ETMt is useful for the study of conditioned anxiety in mice. However,
      upon proximal threats (e.g. open arm exposure), mice do not exhibit escape
      behavior as an immediate defensive strategy, suggesting that latency to leave
      open arm is not a useful parameter to evaluate unconditioned fear in this
      species.

PMID- 14684254
TI  - The brain stem but not forebrain independently supports morphine tolerance and
      withdrawal effects in cats.
AB  - We employed polygraphic recordings and behavioral measures to study the effects
      of chronic morphine use upon the isolated forebrain and the decerebrate animal in
      cats with a midbrain transection. Cats received morphine for 12 days, and 24 h
      recording sessions were conducted on days 1 and 11. For the decerebrate cat, the
      percent time of rapid eye movement (REM) sleep was reduced during the 24 h period
      on both days 1 and 11. However, the values on day 11 were consistently higher
      than the values on day 1. Other tolerance indicators were decreases in the number
      of early behavioral signs and in the onset delay for REM sleep, together with an
      increase in onset time for motor activation. After naloxone (day 12) all cats
      displayed "wet shakes," tachypnea and eye squinting, as well as either
      pyloerection, elevated tail, salivation, licking, micturition, and yawning. In
      the isolated forebrain, the percent time for waking increased through the first
      18 h post-morphine on both days 1 and 11. Conversely, the duration of non-REM
      (NREM) sleep and of drowsiness decreased. But importantly, the duration of sleep
      waking states did not vary between days 11 and 1, indicating absence of
      tolerance. Additionally, after naloxone, the isolated forebrain entered NREM
      sleep, contrasting with opposite findings in intact cats. Therefore, while we
      could not demonstrate chronic use effects in the isolated forebrain, the
      decerebrate cat still displayed typical tolerance/withdrawal manifestations. This
      suggests that the effects of chronic opiate use are deeply seated in the brain
      stem, which might help understanding the ingrained nature of physical dependence.

PMID- 14684255
TI  - Sexual imprinting leads to lateralized and non-lateralized expression of the
      immediate early gene zenk in the zebra finch brain.
AB  - Sexual imprinting is an early learning process by which young birds acquire the
      features of a potential sexual partner. The physiological basis of this learning
      process is an irreversible reduction of spine densities in two forebrain areas,
      the lateral neo- and hyperstriatum (LNH) and the medial neo- and hyperstriatum
      (MNH). The aim of the present study was to investigate whether the immediate
      early gene zenk, which has been shown frequently to play a role in plastic
      processes in the song system of zebra finches, may also be involved in the
      structural changes observed in these areas. The first exposure to a female after
      an isolation period enhances zenk expression in a variety of brain areas
      including LNH, MNH, and optic tectum. In contrast to earlier results, it was only
      the neostriatal part of LNH which showed an enhancement on first courtship, while
      exposure to a nestbox enhanced the label within the entire LNH area.
      Unexpectedly, the IEG expression was clearly lateralized in some layers of the
      optic tectum. Because lateralization occurred independent of the experimental
      condition, our study adds to recent results which also support the idea of a
      lateralized organization of the avian visual system.

PMID- 14684256
TI  - Color classification by chimpanzees (Pan troglodytes) in a matching-to-sample
      task.
AB  - We investigated chimpanzees' color classification using a matching-to-sample
      procedure. One of the two subjects had learned symbolic color names through long
      term training, while the other had received less training and had a limited
      understanding of color names. The results showed similar distributions of
      classified colors in a color space, irrespective of the subjects' differential
      color-naming experience. However, the chimpanzee with little color-naming
      experience showed less stable classifications. These results suggest common
      features of color classification in chimpanzees, as well as the influence of
      color experience and/or the learning of color names on the stability of
      classification of colors.

PMID- 14684257
TI  - Increased corticosterone secretion and early-onset of cognitive decline in female
      apolipoprotein E-knockout mice.
AB  - In the present study, the interaction of age and apolipoprotein E (apoE)-genetic
      background on cognitive abilities was investigated in young (5-6 months) and aged
      (14-16 months) female apolipoprotein E-knockout (apoE0/0) and wild-type mice.
      Cognitive abilities are known to be affected by the steroid hormones
      corticosterone and estrogen. Therefore, we measured the activity and reactivity
      of the hypothalamic-pituitary-adrenal (HPA) axis expressed by circadian
      corticosterone concentrations and responses to novelty and controlled the
      regularity of the estrous cycle. Young female apoE0/0 mice acquired the water
      maze task and showed a similar latency and search strategy to locate the platform
      as young female wild-type mice. Similar corticosterone responses to novelty were
      observed in both genotypes. Regularity of the estrous cycle was disturbed in a
      small percentage of the young apoE0/0 female mice. However, in aged female
      apoE0/0 mice water maze performance was impaired with search strategies less
      persistent than in aged wild-type mice. In parallel, increased corticosterone
      concentrations were measured in apoE0/0 mice in response to novelty and during
      the circadian cycle. The percentage of mice with an irregular estrous cycle
      increased with age, but was comparable for apoE0/0 and wild-type mice. Thus,
      although disruption of the apoE gene affects the regularity of the estrous cycle
      in young mice, it is the enhanced corticosterone secretion, which parallels the
      cognitive decline in the aging female apoE0/0 mice.

PMID- 14684258
TI  - 8-OH-DPAT facilitated memory consolidation and increased hippocampal and cortical
      cAMP production.
AB  - Animals were submitted to an associative learning task named
      Pavlovian/instrumental autoshaping (P/I-A) and treated with selective 5-HT1A and
      5-HT7 receptor agonists and antagonists. Next, they were sacrificed, their brains
      removed, dissected and changes on cortical and hippocampal cyclic adenosine
      monophosphate (cAMP) production were determined. Results revealed that, the 8-OH
      DPAT treatment facilitated memory consolidation of autoshaping and that effect
      was blocked completely by WAY100635 and partially by DR4004. WAY100635 or DR4004
      alone had no effect on autoshaping. The cAMP results were complex and yielded no
      clear relationship to the memory results. Thus, cortical and hippocampal
      increased on cAMP production was observed following administration of the 5
      HT(1A/7) agonist 8-OH-DPAT. The memory effect was, completely or partially,
      reversed by the selective antagonists WAY100635 (5-HT1A) or DR4004 (5-HT7),
      respectively.

PMID- 14684259
TI  - Aberrant responses in social interaction of dopamine transporter knockout mice.
AB  - The dopamine (DA) transporter (DAT) controls the temporal and spatial resolution
      of dopaminergic neurotransmission. Disruption of the Dat1 gene in mice leads to
      increased extracellular DA concentrations and reduced expression of D1- and D2
      like receptors in striatum. The mutants are hyperactive in the open field and
      they display deficits in learning and memory. In humans, dopaminergic dysfunction
      has been associated with a number of different psychiatric disorders and some of
      these conditions are accompanied by abnormal social responses. To determine
      whether social responses were also impaired in DAT knockout (KO) mice, behaviors
      of group- and isolation-housed animals were compared. All group-housed animals
      readily established hierarchies. However, the social organizations of the mutants
      were changed over time. Under both group- and isolation-housed conditions,
      mutants exhibited increased rates of reactivity and aggression following mild
      social contact. In isolation, exposure to a novel environment exacerbated these
      abnormal responses. Regardless of housing context, stereotyped and perseverative
      patterns of social responses were a common feature of the KO repertoire. In fact,
      many abnormal behaviors were due to the emergence and predominance of these
      inflexible behaviors. These data suggest that KO mice may serve as a useful
      animal model for understanding not only how DA dysfunction contributes to social
      abnormalities, but also how behavioral inflexibility distorts their social
      responses.

PMID- 14684260
TI  - Involvement of the brain serotonergic system in the locomotor stimulant effects
      of chlorpheniramine in Wistar rats: implication of postsynaptic 5-HT1A receptors.
AB  - Antihistamines, such as chlorpheniramine (CPA), are lipophilic agents which
      readily cross the blood-brain barrier, producing sedation in 10-25% of users.
      However, with excessive doses instead of sedation a stimulating action has been
      reported. The aim of the present study was to investigate the influence of CPA on
      the locomotor activity of the rat in relation to its effects on brain biogenic
      monoamines. Wistar rats were given CPA (40 mg/kg, i.p.) and locomotor activity
      was measured in a photocell cage. Body temperature was also monitored. In
      addition, in three brain subregions (striatum, hypothalamus, and midbrain), the
      levels of 5-HT, NA, DA, as well as their metabolites, were determined by HPLC.
      Soon after injection, CPA produced a significant increase in locomotor activity,
      while a hypothermic response was also induced. In striatum and hypothalamus,
      which are known to be rich in postsynaptic 5-HT1A receptors, we found a
      significant time-dependent increase of 5-HT, correlated with the clearly enhanced
      locomotor activity of the animals. On the contrary, in midbrain, where
      presynaptic 5-HT1A receptors are dominating, no changes could be detected in 5
      HT. In all three brain regions measured, 5-HIAA levels were decreased. The levels
      of the other brain monoamines were only marginally affected. In support of a role
      in receptor specificity, pretreatment with the 5-HT1A receptor agonist 8-OH-DPAT
      (1.25 mg/kg, i.p., two times) or with the 5-HT(1A/B) receptor antagonist pindolol
      (30 mg/kg, i.p., two times), enhanced or blocked, respectively, the
      hyperlocomotion induced by CPA. These findings suggest that the central
      serotonergic system may play a key role in the locomotor stimulant effects of CPA
      in the rat. Moreover, this behavioral component of CPA seems to be primarily
      mediated via the postsynaptic 5-HT1A receptors.

PMID- 14684261
TI  - Artificially-reared female rats show reduced prepulse inhibition and deficits in
      the attentional set shifting task--reversal of effects with maternal-like licking
      stimulation.
AB  - Mammalian nervous system is plastic, particularly during early stages of
      development. Rat neonates that are reared without mothers, grow up to show
      deficient maternal behavior towards their own offspring. The purpose of this
      study was to assess whether maternal behavior deficits, seen in artificially
      reared (AR) female rats, are associated with attentional deficits. Female rat
      pups were reared with or without their mothers, through artificial rearing. In
      adulthood, rats' maternal behavior and performance on attentional tasks (prepulse
      inhibition (PPI) of the startle response and attentional set shifting task) were
      assessed. We found that AR rats showed: decreased maternal pup licking and time
      crouching over pups, less PPI, and more trials to criterion in several stages of
      the attentional set shifting task. Artificially-reared rats that were provided
      with 'maternal-like licking' stimulation, during artificial rearing, were not
      significantly different from mother-reared rats. In addition, there was a
      significant correlation between maternal behaviors and both PPI and the
      performance in the attentional set shifting task.

PMID- 14684262
TI  - Knowledge acquisition in the fuzzy knowledge representation framework of a
      medical consultation system.
AB  - This paper describes the fuzzy knowledge representation framework of the medical
      computer consultation system MedFrame/CADIAG-IV as well as the specific knowledge
      acquisition techniques that have been developed to support the definition of
      knowledge concepts and inference rules. As in its predecessor system CADIAG-II,
      fuzzy medical knowledge bases are used to model the uncertainty and the vagueness
      of medical concepts and fuzzy logic reasoning mechanisms provide the basic
      inference processes. The elicitation and acquisition of medical knowledge from
      domain experts has often been described as the most difficult and time-consuming
      task in knowledge-based system development in medicine. It comes as no surprise
      that this is even more so when unfamiliar representations like fuzzy membership
      functions are to be acquired. From previous projects we have learned that a user
      centered approach is mandatory in complex and ill-defined knowledge domains such
      as internal medicine. This paper describes the knowledge acquisition framework
      that has been developed in order to make easier and more accessible the three
      main tasks of: (a) defining medical concepts; (b) providing appropriate
      interpretations for patient data; and (c) constructing inferential knowledge in a
      fuzzy knowledge representation framework. Special emphasis is laid on the
      motivations for some system design and data modeling decisions. The theoretical
      framework has been implemented in a software package, the Knowledge Base Builder
      Toolkit. The conception and the design of this system reflect the need for a user
      centered, intuitive, and easy-to-handle tool. First results gained from pilot
      studies have shown that our approach can be successfully implemented in the
      context of a complex fuzzy theoretical framework. As a result, this critical
      aspect of knowledge-based system development can be accomplished more easily.

PMID- 14684263
TI  - A constrained-syntax genetic programming system for discovering classification
      rules: application to medical data sets.
AB  - This paper proposes a new constrained-syntax genetic programming (GP) algorithm
      for discovering classification rules in medical data sets. The proposed GP
      contains several syntactic constraints to be enforced by the system using a
      disjunctive normal form representation, so that individuals represent valid rule
      sets that are easy to interpret. The GP is compared with C4.5, a well-known
      decision-tree-building algorithm, and with another GP that uses Boolean inputs
      (BGP), in five medical data sets: chest pain, Ljubljana breast cancer,
      dermatology, Wisconsin breast cancer, and pediatric adrenocortical tumor. For
      this last data set a new preprocessing step was devised for survival prediction.
      Computational experiments show that, overall, the GP algorithm obtained good
      results with respect to predictive accuracy and rule comprehensibility, by
      comparison with C4.5 and BGP.

PMID- 14684264
TI  - WeAidU-a decision support system for myocardial perfusion images using artificial
      neural networks.
AB  - This paper presents a computer-based decision support system for automated
      interpretation of diagnostic heart images (called WeAidU), which is made
      available via the Internet. The system is based on image processing techniques,
      artificial neural networks (ANNs) and large well-validated medical databases. We
      present results using artificial neural networks, and compare with two other
      classification methods, on a retrospective data set containing 1320 images from
      the clinical routine. The performance of the artificial neural networks detecting
      infarction and ischemia in different parts of the heart, measured as areas under
      the receiver operating characteristic curves, is in the range 0.83-0.96. These
      results indicate a high potential for the tool as a clinical decision support
      system.

PMID- 14684265
TI  - Prediction of postoperative morbidity after lung resection using an artificial
      neural network ensemble.
AB  - OBJECTIVE: To propose an ensemble model of artificial neural networks (ANNs) to
      predict cardio-respiratory morbidity after pulmonary resection for non-small cell
      lung cancer (NSCLC). METHODS: Prospective clinical study was based on 489 NSCLC
      operated cases. An artificial neural network ensemble was developed using a
      training set of 348 patients undergoing lung resection between 1994 and 1999.
      Predictive variables used were: sex of the patient, age, body mass index,
      ischemic heart disease, cardiac arrhythmia, diabetes mellitus, induction
      chemotherapy, extent of resection, chest wall resection, perioperative blood
      transfusion, tumour staging, forced expiratory volume in 1s percent (FEV(1)%),
      and predicted postoperative FEV(1)% (ppoFEV(1)%). The analysed outcome was the
      occurrence of postoperative cardio-respiratory complications prospectively
      recorded and codified. The artificial neural network ensemble consists of 100
      backpropagation networks combined via a simple averaging method. The
      probabilities of complication calculated by ensemble model were obtained to the
      actual occurrence of complications in 141 cases operated on between January 2000
      and December 2001 and a receiver operating characteristic (ROC) curve for this
      method was constructed. RESULTS: The prevalence of cardio-respiratory morbidity
      was 0.25 in the training and 0.30 in the validation series. The accuracy for
      morbidity prediction (area under the ROC curve) was 0.98 by the ensemble model.
      CONCLUSION: In this series an artificial neural network ensemble offered a high
      performance to predict postoperative cardio-respiratory morbidity.

PMID- 14684266
TI  - Use of genetic algorithms for neural networks to predict community-acquired
      pneumonia.
AB  - BACKGROUND: Genetic algorithms have been used to solve optimization problems for
      artificial neural networks (ANN) in several domains. We used genetic algorithms
      to search for optimal hidden-layer architectures, connectivity, and training
      parameters for ANN for predicting community-acquired pneumonia among patients
      with respiratory complaints. METHODS: Feed-forward back-propagation ANN were
      trained on sociodemographic, symptom, sign, comorbidity, and radiographic outcome
      data among 1044 patients from the University of Illinois (the training cohort),
      and were applied to 116 patients from the University of Nebraska (the testing
      cohort). Binary chromosomes with genes representing network attributes, including
      the number of nodes in the hidden layers, learning rate and momentum parameters,
      and the presence or absence of implicit within-layer connectivity using a
      competition algorithm, were operated on by various combinations of crossover,
      mutation, and probabilistic selection based on network mean-square error (MSE),
      and separately on average cross entropy (ENT). Predictive accuracy was measured
      as the area under a receiver-operating characteristic (ROC) curve. RESULTS: Over
      50 generations, the baseline genetic algorithm evolved an optimized ANN with nine
      nodes in the first hidden layer, zero nodes in the second hidden layer, learning
      rate and momentum parameters of 0.5, and no within-layer competition
      connectivity. This ANN had an ROC area in the training cohort of 0.872 and in the
      testing cohort of 0.934 (P-value for difference, 0.181). Algorithms based on
      cross-generational selection, Gray coding of genes prior to mutation, and
      crossover recombination at different genetic levels, evolved optimized ANN
      identical to the baseline genetic strategy. Algorithms based on other strategies,
      including elite selection within generations (training ROC area 0.819), and
      inversions of genetic material during recombination (training ROC area 0.812),
      evolved less accurate ANN. CONCLUSION: ANN optimized by genetic algorithms
      accurately discriminated pneumonia within a training cohort, and within a testing
      cohort consisting of cases on which the networks had not been trained. Genetic
      algorithms can be used to implement efficient search strategies for optimal ANN
      to predict pneumonia.

PMID- 14684267
TI  - An overview of current delivery systems in cancer gene therapy.
AB  - The main objective in gene therapy is the development of efficient, non-toxic
      gene carriers that can encapsulate and deliver foreign genetic materials into
      specific cell types such as cancerous cells. During the past two decades,
      enormous research in the area of gene delivery has been conducted worldwide, in
      particular for cancer gene therapy application. Viral vectors are biological
      systems derived from naturally evolved viruses capable of transferring their
      genetic materials into the host cells. Many viruses including retrovirus,
      adenovirus, herpes simplex virus (HSV), adeno-associated virus (AAV) and pox
      virus have been modified to eliminate their toxicity and maintain their high gene
      transfer capability. The limitations associated with viral vectors, however, in
      terms of their safety, particularly immunogenicity, and in terms of their limited
      capacity of transgenic materials, have encouraged researchers to increasingly
      focus on non-viral vectors as an alternative to viral vectors. Non-viral vectors
      are generally cationic in nature. They include cationic polymers such as
      poly(ethylenimine) (PEI) and poly(L-lysine) (PLL), cationic peptides and cationic
      liposomes. The newly described liposomal preparation LPD
      (liposomes/protamine/DNA), for example, has shown superiority over conventional
      liposomes/DNA complexes (lipoplexes). Although non-viral vectors are less
      efficient than viral ones, they have the advantages of safety, simplicity of
      preparation and high gene encapsulation capability. This article reviews the most
      recent studies highlighting the advantages and the limitations of various types
      of gene delivery systems used in cancer gene therapy.

PMID- 14684268
TI  - Absorption enhancers in pulmonary protein delivery.
AB  - Extensive research efforts have been directed towards the systemic administration
      of therapeutic proteins and poorly absorbed macromolecules via various
      nontraditional, injection-free administration sites such as the lung. As a portal
      for noninvasive delivery, pulmonary administration possesses several attractive
      features including a large surface area for drug absorption. Nevertheless,
      achieving substantial bioavailability of proteins and macromolecules by this
      route has remained a challenge, chiefly due to poor absorption across the
      epithelium. The lungs are relatively impermeable to most drugs when formulated
      without an absorption enhancer/promoter. In an attempt to circumvent this
      problem, many novel absorption promoters have been tested for enhancing the
      systemic availability of drugs from the lungs. Various protease inhibitors,
      surfactants, lipids, polymers and agents from other classes have been tested for
      their efficacy in improving the systemic availability of protein and
      macromolecular drugs after pulmonary administration. The purpose of this article
      is to provide the reader with a summary of recent advances made in the field of
      pulmonary protein delivery utilizing absorption enhancers. This report reviews
      the various agents used to increase the bioavailability of these drugs from the
      lungs, their mechanisms of action and effectiveness, and their potential for
      toxicity.

PMID- 14684269
TI  - In vitro and in vivo correlation of buserelin release from biodegradable implants
      using statistical moment analysis.
AB  - Here we investigated the possibility to develop different levels of correlation
      between in vitro drug release profiles and in vivo pharmacokinetic parameters for
      three Buserelin implant formulations. The in vitro and in vivo data were analyzed
      using model-independent and model-dependent methods. Since diffusion, dissolution
      and erosion effects influence drug release in most cases a simple kinetic model
      is unlikely to explain the overall in vivo release behavior. Thus the in vitro
      drug release curves were analyzed according to the theoretical models of Higuchi
      and Korsmeyer-Peppas. For the formulation with predominant diffusion controlled
      release level A IVIVC could be established (R2=0.986). Independent on drug
      release mechanism, a level B correlation between the mean in vitro dissolution
      time (MDT) and mean in vivo residence time (MRT) was obtained with a correlation
      coefficient of 0.983. Finally, level C correlation were observed when single in
      vitro parameters, e.g. T50% (time required to release 50% of drug in vitro) where
      compared with single in vivo parameters like AUC. This study suggests that a
      level B correlation could be achieved even when drug release occurs by a
      combination of diffusion and erosion processes. More sophisticated in vitro
      models mimicking drug release under in vivo conditions are clearly desirable for
      parenteral depot formulations.

PMID- 14684270
TI  - Synthesis and characterization of branched poly(L-glutamic acid) as a
      biodegradable drug carrier.
AB  - Polymeric drug delivery systems are used not only to improve aqueous solubility
      of drug molecules but also to achieve desirable pharmacokinetics and an enhanced
      therapeutic index. New biodegradable polymers are needed to improve the
      biodistribution and targeting-ability of polymeric carriers. In this study, the
      synthesis and characterization of branched poly(L-glutamic acid) (PG) containing
      multiple PG chains centered on a poly(amidoamine) (PAMAM) dendrimer or
      polyethyleneimine (PEI) cores were described. The branched PG polymers were
      obtained by ring-opening polymerization of benzyl ester of L-glutamic acid N
      carboxyanhydride using PAMAM or PEI as the initiator. These polymers were
      degradable in the presence of the lysosomal enzyme cathepsin B, albeit more
      slowly than linear PG. Unlike conventional linear PG, each branched PG possessed
      multiple terminal amino groups. This made it possible to attach multiple
      targeting moieties selectively to the termini of branched PG. Conjugation of
      monofunctional or heterodifunctional polyethylene glycol to the chain ends of
      branched PG was demonstrated in the presence of side chain carboxyl groups.
      Furthermore, folic acid, a model targeting moiety, and the near-infrared dye
      indocyanine green, a model diagnostic agent, were successfully conjugated to the
      terminal amino groups and the side chain carboxyl groups of branched PG,
      respectively. The resulting conjugate had reduced nonspecific interaction and
      bound selectively to tumor cells expressing folate receptors. Thus, branched PG
      may be useful as a polymeric carrier for targeted drug delivery.

PMID- 14684271
TI  - Hydrolysis of the oil phase of a W/O/W emulsion by pancreatic lipase.
AB  - W/O/W emulsions are expected to protect bioactive substances from degradation by
      pancreatic enzymes. We investigated the enzymatic hydrolysis of the oil phase and
      release of a marker substance from the inner-aqueous phase to the outer-aqueous
      phase using an artificial digestive fluid. Octanoic acid triacylglycerol (C8TG)
      was used as the oil phase. W/O/W emulsions were prepared by two-step
      homogenization and succeeding membrane filtration. When the artificial digestive
      fluid containing lipase and gall was added to the emulsion, release of the marker
      substance from the inner-phase solution, oil-phase hydrolysis, and emulsion
      coalescence occurred in that order. When a coarse emulsion and 0.2- and 0.8
      microm membrane-filtered fine emulsions were treated with the fluid for 1 h, the
      degrees of C8TG hydrolysis were 3.8%, 55% and 57%, the fractions of the marker
      substance released from the inner-water phase were 2.7%, 89% and 72%, and the
      median diameters of the oil droplets were changed from 32 to 23 microm, 0.71 to
      27 microm, and from 2.2 to 26 microm, respectively. These results suggested that
      the diameter of the oil droplets in the W/O/W emulsion significantly affected the
      release profile of the marker loaded in the inner-water phase of the emulsion.

PMID- 14684272
TI  - Bacterial ghosts as novel advanced drug delivery systems: antiproliferative
      activity of loaded doxorubicin in human Caco-2 cells.
AB  - Systemic application of anticancer drugs often causes severe toxic side effects.
      To reduce the undesired effects, advanced drug delivery systems are needed which
      are based on specific cell targeting vehicles. In this study, bacterial ghosts
      from Mannheimia haemolytica were used for site-specific delivery of doxorubicin
      (DOX) to human colorectal adenocarcinoma cells (Caco-2). Bacterial ghosts are non
      denatured envelopes of Gram-negative bacteria with fully intact surface
      structures for specific attachment to mammalian cells. The in vitro release
      profile of DOX-ghosts demonstrated that the loaded drug was non-covalently
      associated with the bacterial ghosts and that the drug delivery vehicles
      themselves represent a slow release system. Adherence studies showed that the M.
      haemolytica ghosts more efficiently than E. coli ghosts targeted the Caco-2 cells
      and released the loaded DOX within the cells. Cytotoxicity assays revealed that
      the DOX-ghosts exhibited potent antiproliferative activities on Caco-2 cells as
      the DOX associated with ghosts was two magnitude of orders more cytotoxic than
      free DOX provided in the medium at the same concentrations. Notably, a
      significant reduction in the cell viability was measured with DOX-ghosts at low
      DOX concentrations, which had no inhibitory effect when applied as free DOX after
      incubation for 16 h or when applied at higher concentrations for only 10 min to
      the cells. As the higher antiproliferative effects of DOX on Caco-2 cells were
      mediated by the specific drug targeting properties of the bacterial ghosts, the
      bacterial ghost system represents a novel platform for advanced drug delivery.

PMID- 14684273
TI  - Osmotic drug delivery using swellable-core technology.
AB  - Swellable-core technology (SCT) formulations that used osmotic pressure and
      polymer swelling to deliver drugs to the GI tract in a reliable and reproducible
      manner were studied. The SCT formulations consisted of a core tablet containing
      the drug and a water-swellable component, and one or more delivery ports. The in
      vitro and in vivo performance of two model drugs, tenidap and sildenafil,
      formulated in four different SCT core configurations: homogeneous-core (single
      layer), tablet-in-tablet (TNT), bilayer, and trilayer core, were evaluated. In
      vitro dissolution studies showed that the drug-release rate was relatively
      independent of the core configuration but the extent of release was somewhat
      lower for the homogeneous-core formulation, particularly under non-sink
      conditions. The drug-release rate was slower with increasing coating thickness
      and decreasing coating permeability, and was relatively independent of the drug
      loading and the number and size of the delivery ports. The drug-release rates
      were similar for the two model drugs despite significant differences in their
      physicochemical properties. Tablet-recovery and pharmacokinetic studies conducted
      in beagle dogs showed that the in vivo release of drug from SCT formulations was
      comparable to the in vitro drug release.

PMID- 14684274
TI  - Polyvinylpyrrolidone-drug conjugate: synthesis and release mechanism.
AB  - Covalent conjugates of polyvinylpyrrolidone (PVP) with para-nitroaniline (PNA)
      were synthesized as a model PVP-drug conjugate, and PNA release was evaluated in
      vitro. Pyrrolidone ring opening with subsequent t-BOC protection of the
      pyrrolidone nitrogen and reaction with PNA in methylene chloride (CH2Cl2)
      produced a PVP-PNA conjugate with 3% of the pyrrolidone groups modified. Rates of
      PNA release from N-deprotected conjugates were twofold greater than those that
      were N-protected, indicating participation of the pyrrolidone N in release.
      Additional studies with monomeric analogs supported intramolecular base catalysis
      rather than lactam formation as the mechanism of this involvement. The approach
      serves as a prototype for the conjugation of other drugs with primary and
      secondary amine functional groups with PVP, including peptides and proteins.

PMID- 14684275
TI  - Transforming growth factor-beta 1 release from oligo(poly(ethylene glycol)
      fumarate) hydrogels in conditions that model the cartilage wound healing
      environment.
AB  - This research demonstrates that controlled material degradation and transforming
      growth factor-beta1 (TGF-beta1) release can be achieved by encapsulation of TGF
      beta1-loaded gelatin microparticles within the biodegradable polymer
      oligo(poly(ethylene glycol) fumarate) (OPF), so that these microparticles
      function as both a digestible porogen and a delivery vehicle. Release studies
      performed with non-encapsulated microparticles confirmed that at normal
      physiological pH, TGF-beta1 complexes with acidic gelatin, resulting in slow
      release rates. At pH 4.0, this complexation no longer persists, and TGF-beta1
      release is enhanced. However, by encapsulating TGF-beta1-loaded microparticles in
      a network of OPF, release at either pH can be diffusionally controlled. For
      instance, after 28 days of incubation at pH 4.0, final cumulative release from
      non-encapsulated microparticles crosslinked in 10 and 40 mM glutaraldehyde (GA)
      was 75.4+/-1.6% and 76.6+/-1.1%, respectively. However, when either microparticle
      formulation was encapsulated in an OPF hydrogel (noted as OPF-10 mM and OPF-40
      mM, respectively), these values were reduced to 44.7+/-14.6% and 47.4+/-4.7%.
      More interestingly, release studies, in conditions that model the expected
      collagenase concentration of injured cartilage, demonstrated that by altering the
      microparticle crosslinking extent and loading within OPF hydrogels, TGF-beta1
      release, composite swelling, and polymer loss could be systematically altered.
      Composites encapsulating less crosslinked microparticles (OPF-10 mM) exhibited
      100% release after only 18 days and were completely degraded by day 24 in
      collagenase-containing phosphate-buffered saline (PBS). Hydrogels encapsulating
      40 mM GA microparticles did not exhibit 100% release or polymer loss until day
      28. Hydrogels with no microparticle component demonstrated only 79.3+/-9.2%
      release and 89.2+/-3.4% polymer loss after 28 days in enzyme-containing PBS.
      Accordingly, these studies confirm that the rate of TGF-beta1 release and
      material degradation can be controlled by altering key parameters of these novel,
      in situ crosslinkable biomaterials, so that TGF-beta1 release and scaffold
      degradation may be tailored to optimize cartilage repair.

PMID- 14684276
TI  - Targetable water-soluble polymer-drug conjugates for the treatment of visceral
      leishmaniasis.
AB  - The present work describes the synthesis, characterization, and biological
      evaluation of targetable N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-anti
      leishmanial drug conjugates for the treatment of visceral leishmaniasis (VL).
      Conjugates of HPMA copolymer with NPC1161, an 8-aminoquinoline analog with anti
      leishmanial activity, containing N-acetylmannosamine (ManN) in the side chains
      were synthesized and characterized. In vitro anti-leishmanial efficacy of the
      conjugates was determined in mouse peritoneal macrophages infected with
      Leishmania donovani amastigotes. The conjugates were tested against mammalian KB
      cells for cytotoxicity. The effect of ManN content on uptake was evaluated in RAW
      264 murine macrophages. In vivo anti-leishmanial efficacy was evaluated at 1
      mg/kg intravenous dose in BALB/c mice. HPMA copolymer-NPC1161 conjugates with 5
      mole% or higher ManN content were significantly (p<0.0001) more active (ED50<15
      microg/ml) than nontargeted conjugates (ED50>30 microg/ml). All conjugates were
      relatively nontoxic towards the mammalian cells. Significantly (p<0.003) higher
      uptake was observed for targeted conjugates compared to nontargeted conjugates.
      The targeted conjugates were significantly more effective in vivo (67-80%
      inhibition, p<0.0001) than nontargeted conjugate (47% inhibition). HPMA
      copolymers containing ManN in the side chains can potentially reduce the toxicity
      and increase efficacy of anti-leishmanial drugs for the treatment of VL.

PMID- 14684277
TI  - Microsphere size, precipitation kinetics and drug distribution control drug
      release from biodegradable polyanhydride microspheres.
AB  - A thorough understanding of the factors affecting drug release mechanisms from
      surface-erodible polymer devices is critical to the design of optimal delivery
      systems. Poly(sebacic anhydride) (PSA) microspheres were loaded with three model
      drug compounds (rhodamine B, p-nitroaniline and piroxicam) with a range of
      polarities (water solubilities). The drug release profiles from monodisperse
      particles of three different sizes were compared to release from polydisperse
      microspheres. Each of the model drugs exhibited different release mechanisms.
      Drug distribution within the polymer was investigated by laser scanning confocal
      microscopy and scanning electron microscopy. Rhodamine, the most hydrophilic
      compound investigated, was localized strongly toward the microsphere surface,
      while the much more hydrophobic compound, piroxicam, distributed more evenly.
      Furthermore, all three compounds were most uniformly distributed in the smallest
      microspheres, most likely due to the competing effects of drug diffusion out of
      the nascent polymer droplets and the precipitation of polymer upon solvent
      extraction, which effectively "traps" the drug in the polymer matrix. The
      differing drug distributions were manifested in the drug release profiles.
      Rhodamine was released very quickly independent of microsphere size. Thus,
      extended release profiles may not be obtainable if the drug strongly
      redistributes in the microspheres. The release of p-nitroaniline was more
      prolonged, but still showed little dependence on microsphere size. Hence, when
      water-soluble drugs are encapsulated with hydrophobic polymers, it may be
      difficult to tailor release profiles by controlling microsphere size. The
      piroxicam-loaded microspheres exhibit the most interesting release profiles,
      showing that release duration can be increased by decreasing microsphere size,
      resulting in a more uniform drug distribution.

PMID- 14684278
TI  - Gastrointestinal transit time of nondisintegrating radio-opaque pellets in
      suckling and recently weaned piglets.
AB  - The objective was to determine the gastrointestinal (GI) transit times of pellets
      in piglets at different time points around weaning, as transit times are
      essential criteria to develop oral drug delivery systems. Nondisintegrating radio
      opaque pellets were given orally in order to define the transit times by
      radiography. The radiographs were analysed with a software programme to calculate
      the number of pellets present in the different parts of the GI tract. In suckling
      piglets, the gastric emptying was faster (75% in 1.5 to 3.5 h), and the colonic
      accumulation (to 73%) was greater than in weaned piglets (3 days, 2 and 3 weeks
      postweaning, 65% gastric emptying in 18 h, 75% in 17 h, and 75% in 7 h,
      respectively; maximal colonic accumulations of 48%). Immediately after weaning,
      the transit was markedly prolonged but shortened with increased postweaning time
      (3 days, 2 and 3 weeks postweaning, 85% excretion in 175.5, 77, and 50.5 h,
      respectively). Three weeks postweaning, the transit was no longer affected by
      weaning as transit times were similar to values reported in growing and adult
      pigs, and retention appeared to be restricted to the stomach and the colon. These
      data are of crucial importance in the design of enteric-coated formulations for
      oral administration of vaccines and therapeutics to young piglets and for human
      research using the pig model.

PMID- 14684279
TI  - Cellular association and cytotoxicity of anti-CD74-targeted lipid drug-carriers
      in B lymphoma cells.
AB  - The ability to selectively target anti-cancer drugs via specific ligands against
      antigens expressed on malignant cells could greatly improve the therapeutic
      indices of the drugs. In this paper an anti-CD74 antibody (Ab), LL1, was
      covalently attached to the surface of sterically stabilized lipid drug-carriers
      (emulsions and liposomes) by use of a PEG-based heterobifunctional coupling
      agent. Target cells internalize LL1 very fast and that was found to be true for
      the LL1-lipid drug-carrier complexes as well. During a 24 h in vitro incubation
      with the target Raji B-lymphoma cells about 30% of the added complexes were
      associated with the cells. The corresponding value for drug-carrier without
      targeting ligand was near 0.6%. Displacement experiments showed that free LL1
      competed well with LL1-complexes indicating preserved immunoreactivity. Non
      target cells showed only unspecific association of LL1-complexes. A dioleoylated
      derivative of the anti-cancer drug 3',5'-O-dioleoyl-FUdR (FUdR) (FUdR-dO) loaded
      into LL1-lipid drug-carriers showed good cytotoxic activity. In vitro 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity tests
      against neoplastic B-cells gave IC30 values of 0.45, 1.25, 5.30 and 7.30 microM
      for the prodrug FUdR-dO in LL1-emulsions, LL1-liposomes, emulsions and liposomes,
      respectively. The value for the parent drug FUdR was calculated to 4.35 microM.
      In the light of the extensive and specific delivery of LL1-lipid drug-carriers to
      B-cells and the selective cytotoxicity of the incorporated drug, we infer that
      the complexes may be useful in the selective elimination of circulating malignant
      B-cells in vivo.

PMID- 14684280
TI  - Localization of bovine serum albumin in double-walled microspheres.
AB  - Phase separation of binary blends of various combinations of poly (L-lactide)
      (PLA), and poly (D,L-lactide-co-glycolide) (PLGA), was investigated using
      differential scanning calorimetry (DSC). Based on this phase separation
      phenomenon, double-walled microspheres were fabricated. A model agent, bovine
      serum albumin (BSA) labeled with fluorescein isothiocyanate (FITC-BSA) was
      localized in each layer. Scanning electron microscopy (SEM) and fluorescence
      microscopy (FM) were used to assess the formation of double-walled microspheres
      and the localization of the drug, respectively. When a 1:1 polymer ratio was
      used, the FITC-BSA was localized in the outer layer. When the relative ratio of
      PLGA to PLA was increased to 3:1 using the same overall polymer concentration,
      the FITC-BSA was localized in the inner core. Release studies were carried out to
      evaluate the advantage of double-walled microspheres compared to single walled
      microspheres. Microspheres made with FITC-BSA localized in the inner core
      exhibited a significantly lower initial release rate compared to microspheres
      where the drug was located in the outer layer, or compared to microspheres made
      from PLA only. Hence microspheres with a double-walled morphology have the
      potential for therapeutic use where a high burst might be detrimental.

PMID- 14684281
TI  - Thiolated chitosans: development and in vitro evaluation of a mucoadhesive,
      permeation enhancing oral drug delivery system.
AB  - It was the aim of this study to develop a mucoadhesive, permeation enhancing
      delivery system for orally administered poorly absorbed drugs. Chitosan was
      modified by the immobilisation of thiol groups utilising 2-iminothiolane (Traut's
      reagent). The permeation enhancing effect of the resulting chitosan-4-thio
      butylamidine conjugate (chitosan-TBA conjugate) in combination with the
      permeation mediator glutathione (GSH) was evaluated in Ussing chambers on freshly
      excised small intestinal mucosa from guinea pigs using rhodamine 123 as marker
      for passive drug uptake. The mucoadhesive properties of the chitosan-TBA
      conjugate adjusted to pH 3, 5 and 7 were evaluated via the rotating cylinder
      method and via tensile studies. Release studies were performed with tablets
      comprising 10% cefadroxil used as model drug, 10% GSH and 80% chitosan-TBA
      conjugate pH 3 in 100 mM phosphate buffer pH 6.8 at 37 degrees C. Results showed
      a 3-fold higher permeation enhancing effect of the chitosan-TBA conjugate/GSH
      system in comparison to unmodified chitosan. Mucoadhesion studies revealed that
      the lower the pH of the thiolated chitosan is, the higher are its mucoadhesive
      properties. Release studies showed a sustained release of both cefadroxil and GSH
      over several hours. This delivery system might represent a promising novel tool
      in order to improve the therapeutic efficacy of various drugs which are poorly
      absorbed from the gastrointestinal tract.

PMID- 14684282
TI  - Increased accumulation of PEG-PE micelles in the area of experimental myocardial
      infarction in rabbits.
AB  - Micelles prepared from polyethyleneglycol/phosphatidyl-ethanolamine conjugates
      (PEG-PE) with a size of 7-20 nm and zeta-potential of approximately -18 mV were
      administered i.v. to rabbits with experimental myocardial infarctions. Micelles
      demonstrated a prolonged circulation in the blood (half-life of 2 h) and
      accumulated in the infarction zone with efficiency more than 8-fold higher as
      compared to a non-damaged part of the heart muscle. Obtained results suggest that
      the enhanced permeability and retention (EPR) effect is the primary mechanism of
      accumulation of microparticles in the infarct areas, and that drug carriers such
      as PEG-PE micelles can be used for the delivery of therapeutic or diagnostic
      agents to an area of myocardial infarction.

PMID- 14684283
TI  - Effective protein release from PEG/PLA nano-particles produced by compressed gas
      anti-solvent precipitation techniques.
AB  - Homogeneous PLA/insulin solutions containing different amounts of 350, 750 or
      1900 Da PEG (0-75 wt.% PEG) were processed by semi-continuous compressed CO2 anti
      solvent precipitation to fabricate protein-loaded polymeric nano-particles.
      Proper operative conditions (temperature, pressure, CO2 flow rate and washing
      time) yielded more than 70% product recovery. Scanning electron microscopy,
      transmission electron microscopy and light scattering demonstrated that
      spherical, smooth surfaced particles with size below 1 microm could be obtained.
      X-ray diffraction analysis showed that the gas anti-solvent process modifies the
      polylactide crystalline state. PEG concentration and molecular weight were found
      to affect both optimal operative conditions and morphological and
      biopharmaceutical properties of the final product. Insulin loading yield dropped
      from 95% to 65% by increasing the 1900 Da PEG content from 0 to 75 wt.% or the
      PEG molecular weight from 350 to 1900 Da. The release rate increased
      significantly as the PEG content in the formulation increases. After 3-month
      incubation the drug released raised from 10% to 100% by increasing the 1900 Da
      PEG content from 23 to 7 wt.%. Formulations containing the same 350, 750 or 1900
      Da PEG amount (67 wt.% PEG) displayed similar release profiles. Insulin release
      was found to take place by diffusion mechanism, despite the observation of matrix
      degradation.

PMID- 14684284
TI  - Role of solvent in interactions between fatty acids-based formulations and lipids
      in porcine stratum corneum.
AB  - Fatty acids are commonly used as permeation enhancers to increase skin permeation
      of drug molecules by interacting with the intercellular lipids in the skin. The
      influences of the chain length of the fatty acid in different solvents on the
      stratum corneum (SC) lipids were investigated to further understand the mechanism
      of permeation enhancement of fatty acids. Gravimetric studies showed that SC
      absorbed propylene glycol (PG)-based formulations to a greater extent than
      mineral oil (MO)-based formulations and there was no correlation between the
      nature of fatty acid and the formulation uptake for PG-based formulations. High
      formulation uptake was only observed for MO-based formulation when more
      hydrophilic acids like acetic acid and propionic acid were added. Spectroscopic
      studies revealed that the vibrations of alkyl chains in the stratum corneum
      lipids were dependent on the solvent used. Fatty acids with short chains were
      able to perturb the SC lipids in lipophilic MO but not in PG based on symmetric
      peak shifts. For the PG-based formulations, skin perturbation was attained when
      long chain fatty acid such as oleic acid was present. The results showed that the
      nature of solvent played an important role in the interactions between the fatty
      acids and the intercellular lipids in the SC. These findings would make an
      important contribution to the choice of solvent in transdermal drug delivery
      systems.

PMID- 14684285
TI  - Albumin nanoparticles improved the stability, nuclear accumulation and
      anticytomegaloviral activity of a phosphodiester oligonucleotide.
AB  - The goal of this study was to evaluate the potential of albumin nanoparticles as
      a delivery system for antisense oligonucleotides. Nanoparticles were prepared by
      a coacervation process and cross-linkage with glutaraldehyde. Phosphodiester (PO)
      and phosphorotioate (PS) oligonucleotides were either adsorbed on the surface of
      nanoparticles (PO-NPA and PS-NPA) or incorporated in the nanoparticle matrix (PO
      NPB and PS-NPB). When PO-loaded nanoparticles were incubated with
      phosphodiesterase, only NPB was able to keep the oligonucleotide hybridization
      capability for at least 60 min. The antiviral activity was evaluated in MRC-5
      fibroblasts infected with human cytomegalovirus at a MOI of 0.0035. Both PO
      nanoparticle formulations significantly increased the antiviral activity of free
      PO (P<0.001) and NPB showed slightly higher efficacies than NPA (P<0.05). On the
      other hand, PS exhibited significant higher activity than free PO (P<0.001),
      however, no significant differences were found between PS-nanoparticle and PO
      nanoparticle formulations. These findings were well correlated with the
      intracellular distribution observed for fluorescent oligonucleotide-loaded
      albumin nanoparticles. Even these carriers delayed and decreased the uptake of PO
      by MRC-5 cells, they finally induced a diffused cytoplasmic distribution and
      major nuclear accumulation. In summary, albumin nanoparticles partially protected
      a PO against enzymatic degradation and improved their presence in the nucleus and
      thus, increased its efficiency.

PMID- 14684286
TI  - In vivo sustained release of adenoviral vectors from poly(D,L-lactic-co-glycolic)
      acid microparticles prepared by TROMS.
AB  - We have prepared and characterised injectable adenovirus-loaded polymeric
      microparticles to be used for in vitro and in vivo gene transfer studies.
      Microparticles were prepared by the water-in-oil-in-water solvent evaporation
      method using a novel system where the emulsification process is carried out by
      the turbulent injection of the phases in the total recirculation one-machine
      system (TROMS) apparatus. In vitro studies were performed to assess the amount of
      infectious adenovirus released from the microparticles, showing that these
      microparticles release higher amounts of infectious adenovirus than
      microparticles prepared by standard emulsification techniques. We also tested
      whether sustained release in vivo could overcome the short-lived gene expression
      profile which is typical of adenovirus delivery into muscle. Intramuscular
      injection of adenovirus-loaded microparticles in immunocompetent mice showed
      transgene (beta-galactosidase) expression for at least 7 weeks in two out of four
      muscles injected with adenovirus-loaded microparticles prepared by TROMS, but not
      in control muscles injected with purified adenovirus stocks.

PMID- 14684287
TI  - Controlled plasmid gene transfer to murine renal carcinoma by
      hexadecylphosphocholine.
AB  - We report here that the anticancer drug hexadecylphosphocholine (HPC) can control
      plasmid DNA-mediated gene transfer to renal carcinoma following intratumoral
      administration. Significant improvement of gene expression levels could be
      achieved depending on HPC dose administered. Optimal concentration of HPC co
      injected with plasmid DNA was found to be 0.2% (w/v) showing up to a 10-fold
      increase in reporter gene expression levels when compared to DNA administered
      alone. In vivo gene transfer activity of HPC was not affected by the nature of
      the diluent used, i.e. glucose-based or saline-based isotonic solutions. Although
      in vitro transfection activity of HPC formulations could not be evidenced, a
      liposome leakage assay revealed that HPC could significantly destabilize stable
      lipid membranes suggesting that a possible membrane permeation enhancer activity
      of HPC combined to the physical stress induced by the intratumor injection may
      facilitate plasmid DNA entry inside the cells resulting in increased gene
      expression. HPC/plasmid formulations represent new and attractive non-viral gene
      delivery systems with potential in cancer gene therapy and vaccination.

PMID- 14684288
TI  - The effects of plasmid copy number and sequence context upon transfection
      efficiency.
AB  - It is known that large P1 artificial chromosome (PAC) vectors exhibit reduced
      transfection efficiency in comparison to small plasmid vectors. We investigated
      the dynamics of this effect, by comparing expression from a small plasmid (4.7
      kb) and a PAC vector (111 kb) containing the Enhanced Green Fluorescent Protein
      (EGFP) reporter gene under the control of a P(CMV) promoter. EGFP expression was
      detected by fluorescence activated cell sorting (FACS). We found that the lower
      transfection efficiency of PAC vectors represents both a smaller percentage of
      cells expressing the transgene, and a lower level of expression per cell. We have
      shown that the lower number of plasmid molecules administered per cell in a PAC
      transfection does not explain this effect, and that this effect does not act in
      trans. Surprisingly, dilution of a reporter construct with an irrelevant plasmid
      did not appear to compromise transfection efficiency; in fact, a dilution of 1/10
      slightly enhanced transfection. Therefore, it seems that the plasmid content of a
      liposome-DNA complex need not be 100% reporter construct for optimum transfection
      efficiency. This discovery has potential practical utility in a number of
      applications.

PMID- 14684289
TI  - Design and SAR of thienopyrimidine and thienopyridine inhibitors of VEGFR-2
      kinase activity.
AB  - Novel classes of thienopyrimidines and thienopyridines have been identified as
      potent inhibitors of VEGFR-2 kinase. The synthesis and SAR of these compounds is
      presented, along with successful efforts to diminish EGFR activity present in the
      lead series.

PMID- 14684290
TI  - 3-Methoxycarbonyl-5-nitrophenyl boronic acid: high affinity diol recognition at
      neutral pH.
AB  - Several boronic acids were screened for their ability to bind to diols. 3
      methoxycarbonyl-5-nitrophenyl boronic acid bound to both a catechol dye as well
      as fructose with a comparable affinity to that of an ortho-methylamino
      substituted boronic acid. This work suggests a greater role for appropriately
      functionalized electron deficient boronic acids in diol and carbohydrate
      recognition.

PMID- 14684291
TI  - New orally active PDE4 inhibitors with therapeutic potential.
AB  - Structural optimization of pyrazolopyridine derivative 2, which is one of the
      newly discovered chemical leads for PDE4 inhibitors from our in-house library,
      was carried out successfully. The process of discovery of new orally active PDE4
      inhibitors, which are expected to possess therapeutic potential, is presented and
      their structure-activity relationships are discussed.

PMID- 14684292
TI  - Mechanism-based active site modification of the soybean sterol methyltransferase
      by 26,27-dehydrocycloartenol.
AB  - 26,27-dehydrocycloartenol (26,27-DHC) was shown to be a substrate for the soybean
      sterol methyltransferase (SMT) as well as a mechanism-based inhibitor of enzyme
      action. The K(m) and k(cat) for 26,27-DHC was 10 microM and 0.018 min(-1),
      respectively. SMT catalyzed 26,27-DHC to two products tentatively identified as
      26-homocholesta-9,19-cyclo-23(24)E,26(26')-dienol and 26-homocholesta-9,19-cyclo
      26(26')-en-3beta,24beta-diol by GC-MS. Inhibitor treatment was concentration- and
      time-dependent (pseudo-first-order kinetics). A replot of the half-lives for
      inactivation versus the inverse of the inactivator concentrations gave an
      apparent K(i) of 42 microM and a maximum rate of inactivation of 0.29 min(-1). A
      partition ratio (k(cat)/k(inact)) was calculated to be 0.06.

PMID- 14684293
TI  - Anthranilate 4H-oxazol-5-ones: novel small molecule antibacterial acyl carrier
      protein synthase (AcpS) inhibitors.
AB  - D-optimal design and Projection to Latent Structures (PLS) analysis were used to
      optimize screening hit 5 (B. subtilis AcpS IC(50): 15 microM, B. subtilis MIC:
      >200 microM) into a series of 4H-oxazol-5-one, small molecule, antibacterial,
      AcpS inhibitors. Specifically, 15, 16 and 18 show microM or sub-microM AcpS
      inhibition (IC(50)s: 15: 1.1 microM, 16: 1.5 microM, 18: 0.27 microM) and
      moderate antibacterial activity (MICs: 12.5-50 microM) against B. subtilis, E.
      faecalis ATCC, E. faecalis VRE and S. pneumo+.

PMID- 14684294
TI  - 4-Amino cyclohexylglycine analogues as potent dipeptidyl peptidase IV inhibitors.
AB  - Substituted 4-amino cyclohexylglycine analogues were evaluated for DP-IV
      inhibitory properties. Bis-sulfonamide 15e was an extremely potent 2.6 nM
      inhibitor of the enzyme with excellent selectivity over all counterscreens. 2,4
      difluorobenzenesulfonamide 15b and 1-naphthyl amide 16b, however, combined an
      acceptable in vitro profile with good pharmacokinetic properties in the rat, and
      15b was orally efficacious at 3 mpk in an OGTT in lean mice.

PMID- 14684295
TI  - Tetrahydroisoquinoline based sulfonamide hydroxamates as potent matrix
      metalloproteinase inhibitors.
AB  - The synthesis and MMP inhibitory activity of a series of tetrahydroisoquinoline
      based sulfonamide hydroxamates are described. In nine MMPs tested, most of the
      compounds display potent inhibition activity except for MMP-7. Some subtle
      isozyme selectivity is observed by varying the substituents at the 6- and 7
      positions and aromatic ring of arylsulfonyl groups.

PMID- 14684296
TI  - In vitro gene delivery by a novel human calcitonin (hCT)-derived carrier peptide.
AB  - Gene therapy still awaits a broader application, since safe and efficient gene
      delivery is a major problem. Also for the investigation of signal transduction
      and intracellular trafficking, delivery systems for hydrophilic macromolecules
      that are easy to use are needed. Several peptide-based delivery systems have been
      developed during the last years. We present here a novel carrier peptide derived
      from human calcitonin that is capable of transfecting human neuroblastoma cells
      by complex formation with a plasmid. Because of the peptide's physiological
      origin, cytotoxic effects are not expected.

PMID- 14684297
TI  - Discovery of a novel series of DHODH inhibitors by a docking procedure and QSAR
      refinement.
AB  - A novel series of DHODH inhibitors was developed based on a lead which was
      obtained by a docking procedure and a medicinal chemistry exploration. The
      activity of the initial lead was improved by a QSAR method to yield low nanomolar
      inhibitors.

PMID- 14684298
TI  - Peptide deformylase inhibitors with activity against respiratory tract pathogens.
AB  - A series of analogues of the peptide deformylase (PDF) inhibitor BB-3497 where
      the P3' amide bond was replaced with a ketone functionality is described. The in
      vitro antibacterial profiling of these compounds revealed that they demonstrate
      activity against pathogens associated with respiratory tract infections.

PMID- 14684299
TI  - A facile synthesis of 1-ethoxy-4-cyano-5-ethoxycarbonyl-3H-azuleno[1,2-c]pyran-3
      one, a selective 15-lipoxygenase inhibitor.
AB  - A facile method to synthesize 1-ethoxy-4-cyano-5-ethoxycarbonyl-3H-azuleno[1,2
      c]pyran-3-one, in yield of 92%, which showed selective inhibition effect on 15
      lipoxygenase(soybean source) at IC(50)=24.2+/-2.7 microM while no inhibition
      effect was observed at greater than 300 microM on 5-lipoxygenase, lipid
      peroxidase, phospholipase A(2), protein kinase C, and cyclooxygenase.

PMID- 14684300
TI  - Synthesis and biological evaluation of [4-(2-phenylethenesulfonylmethyl)phenyl]
      quinazolin-4-yl-amines as orally active anti-cancer agents.
AB  - A new series of [4-(2-phenylethenesulfonylmethyl)phenyl]quinazolin-4-yl-amines
      was prepared and tested for its in vitro cytotoxic activity against a panel of 12
      human cancer cell lines. Compounds 9, 15, 24 and 31 showed good in vitro activity
      and were further tested for their in vivo efficacy in the HT-29 human colon adeno
      carcinoma xenograft model. Compound 9 exhibited promising activity in this model.
      Dose-response studies for this compound against HT-29 human colon adeno carcinoma
      xenografts at 100, 200 and 400mg/kg doses were performed.

PMID- 14684301
TI  - Novel O-glycosyl amino acid mimetics as building blocks for O-glycopeptides act
      as inhibitors of galactosidases.
AB  - As potential lead structures for a new class of glycosidase inhibitors the novel
      O-glycosyl amino acid mimetics 3'-O-[2,6-anhydro-D-glycero-L-gluco-heptitol-1-yl]
      L-serine 3 and-L-threonine 4 were synthesized, employing regio- and
      stereoselective aziridine ring opening methodology. They proved to be stable in
      the presence of glycosidases and showed competitive inhibition of alpha
      galactosidase from Aspergillus niger.

PMID- 14684302
TI  - Peptidyl hydroxamic acids as methionine aminopeptidase inhibitors.
AB  - A new class of methionine aminopeptidase (MetAP) inhibitors, which contain an
      internal hydroxamate (N-acyl-N-alkylhydroxylamine) core as the metal-chelating
      group, has been designed, synthesized, and tested. The compounds exhibited
      reversible, competitive inhibition against Escherichia coli MetAP as well as
      human MetAP-1 and MetAP-2. The most potent inhibitor had a K(i) value of 2.5
      microM and >20-fold selectivity toward E. coli MAP.

PMID- 14684303
TI  - The discovery and synthesis of novel adenosine substituted 2,3-dihydro-1H
      isoindol-1-ones: potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1).
AB  - A series of novel 4-(N-acyl)-2,3-dihydro-1H-isoindol-1-ones have been prepared
      from methyl-3-nitro-2-methylbenzoate and linked through various spacers to the
      adenosine derivatives 11 and 12. We found that potent inhibition of poly(ADP
      ribose)polymerase-1 (PARP-1) was achieved when isoindolinone was linked to
      adenosine by a spacer group of a specific length. Introduction of piperazine and
      succinyl linkers between the isoindolinone and adenosine core structures resulted
      in highly potent compounds 8a and 10b, which showed IC(50) values of 45 and 100
      nM, respectively.

PMID- 14684304
TI  - (4-Piperidinylphenyl)aminoethyl amides as a novel class of non-covalent cathepsin
      K inhibitors.
AB  - A series of (4-piperidinylphenyl)aminoethyl amides based on dipeptide anilines
      were synthesized and tested against cathepsin K, cathepsin L and cathepsin B.
      These new non-covalent inhibitors exhibited single-digit nM inhibition of the
      cysteine proteases. Compounds 3 and 7 demonstrated potency in both mouse and
      human osteoclast resorption assays.

PMID- 14684305
TI  - Investigation of novel fumagillin analogues as angiogenesis inhibitors.
AB  - Modification of fumagillin was conducted to develop MetAP-2 inhibitors with
      desirable pharmacological properties. Replacement of the C4 side chain by
      benzyloxime preserves the inhibitory activity against MetAP-2 enzyme. Fumagillin
      analogues containing the C4 benzyloxime moiety were found to be very sensitive to
      the nature of the C6 substituent on the inhibition activity of HUVEC
      proliferation. This lack of correlation between MetAP-2 and HUVEC activities
      might be due to the cellular metabolism of the compounds by epoxide hydrolase,
      which is present in the cell. Compound (E)-3d, containing ethylpiperazinyl
      carbamate at C6 position, exhibited antiangiogenic effects similar to TNP-470 on
      matrigel plug assay and rat corneal micropocket assay.

PMID- 14684306
TI  - Discovery of a potent, selective and orally active canine COX-2 inhibitor, 2-(3
      difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine.
AB  - Structure-activity relationship (SAR) studies of 2-[3-di(and tri)fluoromethyl-5
      arylpyrazol-1-yl]-5-methanesulfonylpyridine derivatives for canine COX enzymes
      are described. This led to the identification of 12a as a lead candidate for
      further progression. The in vitro and in vivo activity of 12a for the canine COX
      2 enzyme as well as its in vivo efficacy and pharmacokinetic properties in dog
      are highlighted.

PMID- 14684307
TI  - Tetrahydronaphthalene-derived amino alcohols and amino ketones as potent and
      selective inhibitors of the delayed rectifier potassium current IKs.
AB  - Class III anti-arrhythmic drugs (e.g., dofetilide) prolong cardiac action
      potential duration (APD) by blocking the fast component of the delayed rectifier
      potassium current (I(Kr)). The block of I(Kr) can result in life threatening
      ventricular arrhythmias (i.e., torsades de pointes). Unlike I(Kr), the role of
      the slow component of the delayed rectifier potassium current (I(Ks)) becomes
      significant only at faster heart rate. Therefore selective blockers of I(Ks)
      could prolong APD with a reduced propensity to cause pro-arrhythmic side effects.
      This report describes structure-activity relationships (SARs) of a series of
      I(Ks) inhibitors derived from 6-alkoxytetralones with good in vitro activity
      (IC(50) > or =30 nM) and up to 40-fold I(Ks)/I(Kr) selectivity.

PMID- 14684308
TI  - 3-D-QSAR of N-substituted 4-amino-3,3-dialkyl-2(3H)-furanone GABA receptor
      modulators using molecular field analysis and receptor surface modelling study.
AB  - We report the theoretical validation of the experimentally observed structure
      activity relationships (SAR) of a set of N-substituted 4-amino-3,3-dialkyl-2(3H)
      furanone GABA receptor modulators showing positive allosteric modulatory activity
      of the GABA(A) receptor similar to that shown by Loreclazole. Efforts were made
      to explain some of the conclusions drawn during this study based on a solitary
      instance of occurrence of the observation within the dataset. Some of the
      conclusions selected for study included (i) the enhanced activity for the R
      enantiomer of a compound, (ii) enhanced activity for a compound with an amide
      type functionality vis-a-vis an amine type functionality at C-4, (iii) enhanced
      activity for a compound with a carboxamide or carbamate type functionality
      linking the end group at C-4 over a compound with only the end group attached,
      provided the alkyl groups attached at C-3 are identical in both cases. The 3-D
      QSAR method of molecular field analysis along with receptor-ligand complex
      stability studies were found to be the most suitable for explaining these
      activities. While the first conclusion was comprehensively proven, significant
      support was obtained in case of the latter two. Further comprehensive study is
      underway and we hope to report them shortly.

PMID- 14684309
TI  - Synthesis and SAR of potent EGFR/erbB2 dual inhibitors.
AB  - A series of 6-alkoxy-4-anilinoquinazoline compounds was prepared and evaluated
      for in vitro inhibition of the erbB2 and EGFR kinase activity. The IC(50) values
      of the best compounds were below 0.10 uM. Further, several of these compounds
      inhibit the growth of erbB2 and EGFR over-expressing tumor cell lines at
      concentrations below 1 uM.

PMID- 14684310
TI  - Differential modulation of the antifungal activity of amphotericin B by natural
      and ent-cholesterol.
AB  - The addition of exogenous ent-cholesterol suppressed the antifungal activity of
      the amphotericin B when added to cultures of Candida albicans, but to a lesser
      extent than natural cholesterol. There were no detectable differences between
      added 2a or 2b on the antifungal activities of jaspamide or bengazole A, two
      unrelated antifungal natural products.

PMID- 14684311
TI  - Non-nucleoside inhibitors of the hepatitis C virus NS5B polymerase: discovery and
      preliminary SAR of benzimidazole derivatives.
AB  - Benzimidazole 5-carboxamide derivatives from a combinatorial screening library
      were discovered as specific inhibitors of the NS5B polymerase of the hepatitis C
      virus (HCV). Initial hit-to-lead activities taking advantage of high-throughput
      parallel synthetic techniques, identified a 1,2-disubstituted benzimidazole 5
      carboxylic acid scaffold as the minimum core for biological activity. Potent
      analogues in this series inhibit the polymerase at low micromolar concentrations
      and provide an attractive "drug-like" lead structure for further optimization and
      the development of potential HCV therapeutics.

PMID- 14684312
TI  - Synthesis of heterotrimeric collagen models containing Arg residues in Y
      positions and analysis of their conformational stability.
AB  - An Arg residue incorporated into the Y-position of collagenous host-guest peptide
      Ac-(Gly-Pro-Hyp)(3)-Gly-Pro-Y-(Gly-Pro-Hyp)(4)-Gly-Gly-NH(2) is reported to
      stabilize the triple helical structure as well as a 4(R)-hydroxyproline (Hyp)
      residue. Here, we synthesized heterotrimeric collagen models containing Arg in Y
      positions utilizing the cystine knot strategy. Analysis of their thermal
      transition temperatures using circular dichroism spectrometry demonstrated
      unexpected decrease in the triple helical stability as the number of Arg
      increased. The obtained results indicated that an Arg residue in a Y-position is
      not always an equivalent of a Hyp residue, and that it possesses a potential
      helix destabilizing effect.

PMID- 14684313
TI  - An efficient synthesis of N3,4-diphenyl-5-(4-fluorophenyl)-2-isopropyl-1H-3
      pyrrolecarboxamide, a key intermediate for atorvastatin synthesis.
AB  - An efficient synthesis of N3,4-diphenyl-5-(4-fluorophenyl)-2-isopropyl-1H-3
      pyrrolecarboxamide, a key intermediate for the synthesis of an effective HMG-CoA
      reductase inhibitor atorvastatin, is described. The synthesis is based on the 1,3
      dipolar cycloaddition reaction of mesoionic munchnone (1,3-oxazolium-5-olate)
      with N1,3-diphenyl-2-propynamide leading to N-benzyl pyrrole, and N-debenzylation
      using sodium in liquid ammonia as key steps.

PMID- 14684314
TI  - Antiproliferative activity of various flavonoids and related compounds: additive
      effect of interferon-alpha2b.
AB  - The antiproliferative activity of several natural and synthetic flavonoids and
      some related compounds was evaluated in vitro against a cell line derived from a
      human cervical carcinoma (WISH cells). According to their activities, the most
      potent derivatives were 2'-nitroflavone (14), 2',6-dinitroflavone (15) and the n
      buthyl ester of caffeic acid (29). When these compounds were tested in the
      presence of recombinant human interferon-alpha2b (rhIFN-alpha2b), a cytokine
      exhibiting an antimitogenic action on WISH cells, an additive effect on cell
      growth inhibition was observed. Time course studies of the antiproliferative
      action exerted by the active derivatives or the rhIFN-alpha2b suggested that
      these compounds induced cell death.

PMID- 14684315
TI  - An electrochemical device for the assay of the interaction between a dioxin
      receptor and its various ligands.
AB  - Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that
      mediates the toxic and biological effects of a variety of chemicals. Although a
      significant amount of information is available with respect to the planar
      aromatic hydrocarbon AhR ligands, information on the actual spectrum of chemical
      structures that can bind to and activate the AhR is insufficient. In order to
      determine the binding affinities of chemicals to the human AhR (hAhR), we
      constructed an electrochemical system which carries the hAhR ligand-binding
      domain on the electrode surface. The recombinant hAhR ligand-binding domain that
      was expressed in Escherichia coli using a T7 expression system was immobilized on
      a gold electrode. The specificity of this biosensor based on a ligand-receptor
      interaction was comparable to other in vitro screening methods. The receptor
      modified electrode can rapidly detect the binding of ligands to hAhR. The
      electrochemical measurement can be carried out within just 5 min. This
      electrochemical screening system is rapid, low in cost, and adaptable to high
      throughput applications without sacrificing either sensitivity or selectivity.

PMID- 14684316
TI  - Novel galbonolide derivatives as IPC synthase inhibitors: design, synthesis and
      in vitro antifungal activities.
AB  - A series of novel galbonolide derivatives having a modified methyl enol ether
      moiety were prepared in total synthetic procedures and evaluated for their in
      vitro antifungal activities. The antifungal activity was labile to modification
      of the enol ether functionality and almost all of the modified compounds lacked
      the activity except for the analogue with an introduction of a methylthio group
      at the C-6 position, which retained a modest antifungal potency against
      Cryptococcus neoformans.

PMID- 14684317
TI  - Synthesis of antitumor 6-alkylidenepenicillanate sulfones and related 3
      alkylidene-2-azetidinones.
AB  - 6-alkylidenepenicillanate sulfoxides and sulfones were synthesized on the base of
      6-oxopenicillanate esters. The targeted splitting of their thiazolidine ring led
      to the formation of 3-alkylidene substituted 4-heteryldithio and 4-methylsulfonyl
      azetidin-2-ones. Some of mono and bicyclic beta-lactams revealed potent cytotoxic
      properties towards monolayer tumor cells in <10-microM concentrations.

PMID- 14684318
TI  - The difluoromethylene group as a replacement for the labile oxygen in steroid
      sulfates: a new approach to steroid sulfatase inhibitors.
AB  - Several estrone sulfate and estradiol sulfate analogues, in which the sulfate
      group was replaced with an alpha,alpha-difluoromethylenesulfonate group or an
      alpha,alpha-difluoromethylenetetrazole group, were examined as inhibitors of
      steroid sulfatase (STS). These compounds were 4.5-10.5 times more potent than
      their non-fluorinated analogues. Moreover, the presence of the fluorines changed
      the mode of inhibition from mixed to competitive. The inhibitor bearing the
      alpha,alpha-difluoromethylenetetrazole group exhibited an affinity for STS
      approaching that of the natural STS substrate, estrone sulfate. Possible reasons
      for the enhanced affinity of the fluorinated compounds compared to their non
      fluorinated counterparts are discussed.

PMID- 14684319
TI  - Phenolic thiazoles as novel orally-active neuroprotective agents.
AB  - Novel phenolic thiazoles compounds were prepared which demonstrated potent
      antioxidant activity and potent in vivo neuroprotection in mitochondrial toxin
      models and also possess good oral bioavailability.

PMID- 14684320
TI  - Synthesis of hydrophilic and flexible linkers for peptide derivatization in solid
      phase.
AB  - Four N-Fmoc protected polyoxyethylene-based amino acid type linkers were designed
      and synthesized for peptide derivatization in solid phase. Three of them were
      obtained in a crystalline form. The crystallized linkers can be stored at 4
      degrees C for 2 years without significant decomposition. Protocols for
      biotinylation and fluorescent labeling of peptides in solid phase were developed.
      The linkers also provide good ionization ability for single-bead mass
      spectrometry analysis of peptides.

PMID- 14684321
TI  - Substituted furo[3,2-b]pyridines: novel bioisosteres of 5-HT 1F receptor
      agonists.
AB  - Synthesis and evaluation of a series of 2,3,5- and 3,5-substituted furo[3,2
      b]pyridines were undertaken in order to investigate their utility as bioisosteres
      of 5-HT(1F) receptor agonist indole analogues, 1-3. The replacement proved to be
      effective, providing compounds with similar 5-HT(1F) receptor affinity and
      improved selectivity when compared with the indole analogues. Through these
      studies we identified 4-fluoro-N-[3-(1-methyl-piperidin-4-yl)-furo[3,2-b]pyridin
      5-yl]-benzamide (5), a potent and selective 5-HT(1F) receptor agonist with the
      potential to treat acute migraine.

PMID- 14684322
TI  - Novel semi-synthetic nocathiacin antibiotics: synthesis and antibacterial
      activity of bis- and mono-O-alkylated derivatives.
AB  - Several semi-synthetic bis- and mono-O-alkyl nocathiacin derivatives were
      synthesized and evaluated for antibacterial activity. Mono-O-alkyl N
      hydroxyindole analogues 3a-l were prepared by regioselective alkylation. Bis-O
      alkyl nocathiacins 4a-f were obtained by treatment with base and excess
      electrophile. A one-pot protection-alkylation-deprotection strategy was developed
      for the preparation of mono-O-alkyl hydroxypyridine analogues 5a,b. Most of the
      bis- and mono-O-alkyl nocathiacins maintained good in vitro activity but showed
      reduced in vivo efficacy when compared with the natural product. The excellent in
      vivo activity and improved water solubility of phosphate analogues 3m and 4g
      suggest their use as potential pro-drugs.

PMID- 14684323
TI  - Aminoimidazoles as bioisosteres of acylguanidines: novel, potent, selective and
      orally bioavailable inhibitors of the sodium hydrogen exchanger isoform-1.
AB  - Inhibition of the sodium hydrogen exchanger isoform-1 (NHE-1) has been shown to
      limit damage to the myocardium under ischemic conditions in animals. While most
      known NHE-1 inhibitors are acylguanidines, this report describes the design and
      synthesis of a series of heterocyclic inhibitors of NHE-1 including
      aminoimidazoles with undiminished in vitro activity and oral bioavailability.

PMID- 14684325
TI  - Design and synthesis of aminopropyl tetrahydroindole-based indolin-2-ones as
      selective and potent inhibitors of Src and Yes tyrosine kinase.
AB  - A novel series of substituted 3-[3-(aminopropyl)-4,5,6,7-tetrahydro-1H-indol-2
      ylmethylene]-1,3-dihydro-indole-2-ones was discovered as potent inhibitors of the
      non-receptor tyrosine kinase Src and Yes. A structure-activity relationship was
      developed in order to optimize their potency and selectivity. Syntheses of these
      compounds are also described herein.

PMID- 14684324
TI  - The design and synthesis of a novel quinolizidine template for potent opioid and
      opioid receptor-like (ORL1, NOP) receptor ligands.
AB  - A new class of high affinity opioid and opioid receptor-like receptor (ORL1
      receptor, NOP receptor) ligands has been designed by conformational restriction
      of piperidine-based NOP receptor ligands, resulting in a novel quinolizidine
      scaffold. Different modifications of the pendant functional groups on the
      scaffold provide differential activities at the opioid and NOP receptors. While
      the conformational rigidity will provide an improved understanding of the NOP and
      opioid receptor binding pockets, these compounds also provide a new template for
      the design of novel opiate and NOP ligands.

PMID- 14684326
TI  - Synthesis and cardiovascular activity of metoprolol analogues.
AB  - The synthesis of four novel analogues of metoprolol, a well-known beta1-blocker
      used to reduce arterial blood pressure, is described. The preparation of (2S,2'S)
      7, (2R,2'S)-7, (2R,2'R)-8, and (2S,2'R)-8 was based on the reaction of racemic 2
      [4-(2'-methoxyethyl)-phenoxymethyl]-oxirane (4) with (R)- or (S)-2-amino-1
      butanol. Salient characteristics of analogues 7 and 8 relative to metoprolol are
      the incorporation of an additional stereogenic center, as well as a methyl group
      and a hydroxyl function on the nitrogen-containing chain. These novel derivatives
      present significant hypotensive and bradycardiac activity, although no blocking
      action toward beta1 and beta2 adrenergic receptor.

PMID- 14684327
TI  - Conformationally-flexible benzamide analogues as dopamine D3 and sigma 2 receptor
      ligands.
AB  - A series of conformationally-flexible analogues was prepared and their affinities
      for D2-like dopamine (D2, D3 and D4) were determined using in vitro radioligand
      binding assays. The results of this structure-activity relationship study
      identified one compound, 15, that bound with high affinity (K(i) value=2nM) and
      moderate selectivity (30-fold) for D3 compared to D2 receptors. In addition, this
      series of compounds were also tested for affinity at sigma1 and sigma2 receptors.
      We evaluated the affinity of these dopaminergic compounds at sigma receptors
      because (a) several antipsychotic drugs, which are high affinity antagonists at
      dopamine D2-like receptors, also bind to sigma receptors and (b) sigma receptors
      are expressed ubiquitously and at high levels (picomoles per mg proteins). It was
      observed that a number of analogues displayed high affinity and excellent
      selectivity for sigma2 versus sigma1 receptors. Consequently, these novel
      compounds may be useful for characterizing the functional role of sigma2
      receptors and for imaging the sigma2 receptor status of tumors in vivo with PET.

PMID- 14684328
TI  - Inactivation of gamma-aminobutyric acid aminotransferase by (S)-4-amino-4,5
      dihydro-2-furancarboxylic acid does not proceed by the expected aromatization
      mechanism.
AB  - Inactivation of pyridoxal 5'-phosphate (PLP)-dependent gamma-aminobutryic acid
      aminotransferase by (S)-4-amino-4,5-dihydro-2-furancarboxylic acid (SADFA) gives
      pyridoxamine 5'-phosphate, not the expected SADFA-PLP aromatization product.
      Inactivation appears to proceed by a Michael addition/hydrolysis mechanism
      instead.

PMID- 14684329
TI  - Highly potent PDE4 inhibitors with therapeutic potential.
AB  - Based on the hypothesis that the dose-limiting side effects of PDE4 inhibitors
      could be mediated via the central nervous system (CNS), design and synthesis of a
      hydrophilic analogue is considered to be one approach to improving the side
      effect profile of Ariflo 1. Water-soluble piperidine derivatives were found to
      possess therapeutic potential.

PMID- 14684330
TI  - Novel targeting strategy based on multimeric ligands for drug delivery and
      molecular imaging: homooligomers of alpha-MSH.
AB  - Homooligomers constructed with 4- and 6-amino acid fragments of melanocortin
      (alpha-MSH) bind with higher affinity and with apparent cooperativity to
      melanocortin receptor, compared to their constituent monomers. Individual ligands
      were tethered with various spacers of different length and rigidity and the
      influence of spacers on binding was studied. Binding assays were performed on
      cells transfected with the melanocortin receptor, hMC4R. There is a 5-7-fold
      decrease in the EC(50) with the addition of each subunit, going from monomer to
      trimer. The Hill coefficient increases from 0.76 for the monomer to 1.12 for the
      dimer and 1.35 for the trimer. These data show a general trend of increasing
      avidity with increasing number of ligands in oligomers.

PMID- 14684331
TI  - Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently
      inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme
      IX.
AB  - E7070 [N-(3-chloro-7-indolyl)-1,4-benzenedisulfonamide] is an anticancer drug
      candidate under clinical development for the treatment of several types of
      cancers. We prove here that this compound also acts as a potent carbonic
      anhydrase (CA) inhibitor. Similarly to the clinically used drugs acetazolamide,
      methazolamide and topiramate, E7070 showed inhibition constants in the range of
      15-31nM against isozymes I, II and IX, being slightly less effective as a CA IV
      inhibitor (K(i) of 65nM). The X-ray crystal structure of the adduct of hCA II
      with E7070 revealed unprecedented interactions between the inhibitor and the
      active site, with three different conformations of the chloroindole fragment of
      the inhibitor interacting with different amino acid residues/water molecules of
      the enzyme. A superimposition of these conformations with those of other
      sulfonamide/sulfamate CA inhibitors indicated that similar regions of the hCA II
      active site could be involved in the interaction with inhibitors.

PMID- 14684332
TI  - Carbonic anhydrase inhibitors: N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines
      as topically acting antiglaucoma agents in hypertensive rabbits.
AB  - A series of N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines was prepared by
      reaction of sulfanilamide with different monosaccharides in the presence of
      ammonium chloride. The new compounds were investigated for inhibition of the
      metallo-enzyme carbonic anhydrase (CA, EC 4.2.1.1), involved in aqueous humor
      secretion within the mammalian eye. Isozymes CA I and CA II were strongly
      inhibited by some of these compounds, which showed inhibition constants in the
      range of 510-1200 nM against CA I and 10-25 nM against CA II, similarly to
      clinically used sulfonamides, such as acetazolamide, methazolamide,
      dichlorophenamide, dorzolamide and brinzolamide. The presence of sugar moieties
      in these molecules induced an enhanced water solubility as compared to other
      sulfonamides. In hypertensive rabbits (a widely used animal model of glaucoma),
      two of the new compounds showed strong and long-lasting intraocular pressure
      (IOP) lowering, being more effective than dorzolamide and brinzolamide, the two
      clinically used, topically acting antiglaucoma sulfonamides with CA inhibitory
      properties.

PMID- 14684333
TI  - Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of
      human isozyme II with EMATE, a dual inhibitor of carbonic anhydrases and steroid
      sulfatase.
AB  - The X-ray crystal structure for the adduct of human carbonic anhydrase II (hCA
      II) with estrone-3-O-sulfamate (EMATE), an antiendocrine agent showing both CA
      and estrone sulfatase inhibitory properties, has been resolved at a resolution of
      1.5A. Its binding to the enzyme is similar to that of other
      sulfamates/sulfonamides, considering the interactions of the zinc anchoring
      group, but differs considerably when the steroidal scaffold of the inhibitor is
      analyzed. This part of the inhibitor interacts only within the hydrophobic half
      of the CA active site, interacting with residues Val 121, Phe 131, Val 135 and
      Pro 202, and leaving the hydrophilic half able to accommodate several water
      molecules not present in the uncomplexed enzyme. In addition, a very short bond
      of 1.78A between the zinc ion and the coordinated nitrogen atom of the sulfamate
      moiety is observed, which may explain the high affinity of this inhibitor for hCA
      II (K(i) of 10nM).

PMID- 14684334
TI  - Phenyl thiazolyl urea and carbamate derivatives as new inhibitors of bacterial
      cell-wall biosynthesis.
AB  - Over 50 phenyl thiazolyl urea and carbamate derivatives were synthesized for
      evaluation as new inhibitors of bacterial cell-wall biosynthesis. Many of them
      demonstrated good activity against MurA and MurB and gram-positive bacteria
      including MRSA, VRE and PRSP. 3,4-Difluorophenyl 5-cyanothiazolylurea (3p) with
      clog P of 2.64 demonstrated antibacterial activity against both gram-positive and
      gram-negative bacteria.

PMID- 14684335
TI  - Phe*-Ala-based pentapeptide mimetics are BACE inhibitors: P2 and P3 SAR.
AB  - We describe herein the syntheses and evaluation of a series of C-termini pyridyl
      containing Phe*-Ala-based BACE inhibitors (5-19). In conjunction with four fixed
      residues at the P1 (Phe), P1' (Ala), P2' (Val), and P2' cap (Pyr.), rather
      detailed SAR modifications at P2 and P3 positions were pursued. The promising
      inhibitors emerging from this SAR investigation, 12 and 17 demonstrated very good
      enzyme potency (IC(50)=45 nM) and cellular activity (IC(50)=0.4 microM).

PMID- 14684336
TI  - P3 cap modified Phe*-Ala series BACE inhibitors.
AB  - With the aim of reducing molecular weight and adjusting log D value of BACE
      inhibitors to more favorable range for BBB penetration and better
      bioavailability, we synthesized and evaluated several series of P3 cap modified
      BACE inhibitors obtained via replacement of the P3NHBoc moiety as seen in 3 with
      other polar functional groups such as amino, hydroxyl and fluorine. Several
      promising inhibitors emerging from this P3 cap SAR study (e.g., 15 and 19)
      demonstrated good enzyme inhibitory potencies (BACE-1 IC(50) <50 nM) and whole
      cell activities (IC(50) approximately 1 microM).

PMID- 14684337
TI  - Discovery of a novel bicycloproline P2 bearing peptidyl alpha-ketoamide LY514962
      as HCV protease inhibitor.
AB  - We describe herein the design, syntheses and evaluation of a number of
      bicycloproline P2 bearing HCV protease inhibitors endowed with impressive enzyme
      potency, enzyme selectivity, cellular activity and favorable ADME profiles.

PMID- 14684338
TI  - P1 and P3 optimization of novel bicycloproline P2 bearing tetrapeptidyl alpha
      ketoamide based HCV protease inhibitors.
AB  - With the aim of discovering potent and selective HCV protease inhibitors, we
      synthesized and evaluated a series of 1a based tetrapeptidyl ketoamides with
      additional modification(s) at P1', P1, and P3 positions. As a result of this
      effort, we found that replacement of the P3 valine with tert-leucine resulted in
      the discovery of a series of inhibitors (e.g., 3a, 3c, and 4c) endowed with
      improved enzyme and/or cellular activity relative to 1a. When dosed to F-344 rats
      orally at 50mg/kg, 3a achieved 2.5x higher liver and plasma exposure in
      comparison to that detected with 1a.

PMID- 14684339
TI  - Novel P4 truncated tripeptidyl alpha-ketoamides as HCV protease inhibitors.
AB  - We describe herein the synthesis and evaluation of two series of P-4 truncated
      tripeptidyl alpha-ketoamides as HCV serine protease inhibitors. The most
      promising compound disclosed in this communication 7b demonstrated enzyme binding
      affinity (K(i)) at 0.27 uM.

PMID- 14684340
TI  - Structure-activity relationships of novel potent MurF inhibitors.
AB  - A novel class of MurF inhibitors was discovered and structure-activity
      relationship studies have led to several potent compounds with IC(50)=22
      approximately 70 nM. Unfortunately, none of these potent MurF inhibitors
      exhibited significant antibacterial activity even in the presence of bacterial
      cell permeabilizers.

PMID- 14684341
TI  - Synthesis and nicotinic receptor activity of a hydroxylated tropane.
AB  - (+/-)-3alpha-hydroxy homoepibatidine 4 has been synthesized from the alkaloid
      scopolamine 5 and its properties as a nicotinic agonist assessed. While still
      binding strongly, the compound showed reduced agonist potency for the
      alpha(4)beta(2) nAChR compared with the parent compound epibatidine 1. Compound 4
      also displayed generally similar binding and selectivity profiles at
      alpha(4)beta(2), alpha(2)beta(4), alpha(3)beta(4), and alpha(4)beta(4) nAChR
      subtypes to those for nicotine.

PMID- 14684342
TI  - Exploration of the P1 SAR of aldehyde cathepsin K inhibitors.
AB  - The synthesis and biological activity of a series of aldehyde inhibitors of
      cathepsin K are reported. Exploration of the properties of the S(1) subsite with
      a series of alpha-amino aldehyde derivatives substituted at the P(1) position
      afforded compounds with cathepsin K IC(50)s between 52 microM and 15 nM.

PMID- 14684343
TI  - Mannopeptimycin esters and carbonates, potent antibiotic agents against drug
      resistant bacteria.
AB  - A series of ester and carbonate derivatives of the glycopeptide mannopeptimycin
      alpha (1) with potent activity against G+ bacteria, including the methicillin
      resistant staphylococci and vancomycin-resistant enterococci, was synthesized.
      The SAR data obtained from natural and semisynthetic compounds demonstrated the
      importance of a hydrophobic group in the terminal mannosyl moiety for
      antibacterial activity.

PMID- 14684344
TI  - (2-amino-phenyl)-amides of omega-substituted alkanoic acids as new histone
      deacetylase inhibitors.
AB  - A variety of omega-substituted alkanoic acid (2-amino-phenyl)-amides were
      designed and synthesized. These compounds were shown to inhibit recombinant human
      histone deacetylases (HDACs) with IC(50) values in the low micromolar range and
      induce hyperacetylation of histones in whole cells. They induced expression of
      p21WAF1/Cip1 and caused cell-cycle arrest in human cancer cells. Compounds in
      this class showed efficacy in human tumor xenograft models.

PMID- 14684345
TI  - Resistance towards exonucleases of dinucleotides with stereochemically altered
      internucleotide phosphate bonds.
AB  - Kinetic constants for the hydrolytic susceptibility of the internucleotide
      phosphate bond in normal dinucleotides [e.g., 2'-deoxycytidylyl-(3'>5')-2'
      deoxyuridine (dCpdU) and 2'-deoxyadenylyl-(3'-->5')-2'-deoxycytidine (dApdC)] and
      isomeric dinucleotides [e.g., 2'-deoxycytidylyl-(3'-->5')-1'-deoxy-2'-isouridine
      (dCpisodU) and 1'-deoxy-2'-isoadenylyl-(3'-->5')-2'-deoxycytidine (isodApdC)],
      toward 5'- and 3'-exonucleases, phosphodiesterase I (PDE I) and phosphodiesterase
      II (PDE II) were experimentally determined and remarkable differences emerged.
      The study is of importance in the discovery of nuclease-stable inhibitors of HIV
      integrase, but may also have ramifications in the area of anti-sense
      oligonucleotides of therapeutic interest.

PMID- 14684346
TI  - Rational conversion from antiepileptic polytherapy to monotherapy.
AB  - For patients with epilepsy, the goal of treatment is to achieve seizure freedom
      with minimal or no adverse events. Around 60%-70% of newly diagnosed patients
      will achieve this goal with single antiepileptic drug (AED) therapy, and there is
      universal agreement that prescription of a single agent constitutes best practice
      for such patients. For the 30%-40% of patients with poorly controlled epilepsy,
      treatment options are less clear and many receive add-on therapy with one or more
      AEDs in an attempt to improve seizure control. Because the therapeutic gain from
      adjunctive therapy is often marginal and may be complicated by increased drug
      toxicity, converting individual patients from polytherapy to monotherapy is a
      common clinical problem facing physicians managing patients with epilepsy today.
      Evidence from studies with both standard and new AEDs shows that selected
      patients, including those with previously resistant epilepsy, can be converted
      successfully from polytherapy to monotherapy without loss of seizure control and
      in some cases with improved seizure control. Adverse effects can be minimised
      during the conversion process by slow withdrawal of the first prescribed drug,
      while increasing the daily dose of the add-on AED to achieve optimal therapeutic
      doses/levels for continued monotherapy. Deciding which drug(s) to withdraw and
      which to continue as monotherapy requires adequate consideration of individual
      patient needs with reference to clinical profiles (seizure type and severity),
      previous response to individual AEDs and the pharmacokinetic and pharmacodynamic
      implications of withdrawal.

PMID- 14684347
TI  - Ictal SPECT in a case of pure musicogenic epilepsy.
AB  - A 39-year-old, right-handed woman had seizures for two years which were always
      triggered by exposure to various types of music: the first occurred while she
      listened to a tune she particularly liked, Con Te Partiro, by Andrea Boccelli.
      Other triggering factors were various types of music such as supermarket
      background music and polyphonic singing or instrumental music played by family
      members. The seizures had a stereotyped course: she felt anxious, tearful, then
      occurred slight obtundation, during which she smacked her lips and moved
      restlessly. There was no complete loss of consciousness, but some degree of
      amnesia. She never experienced a generalized tonic-clonic seizure, but reported
      rare spontaneous feelings of deja-vu that had begun at the same time as the
      induced seizures. There were no other spontaneous attacks; only one seizure was
      apparently provoked, not by music but by a loud background noise in her office.
      She was a music lover and a singer. Interictal EEG showed independent slow waves
      over the temporal regions. Several seizures with EEG localisation over the right
      temporal region were elicited after several minutes of exposure to music.
      Monoauricular stimulation with the same music produced a seizure when applied to
      the left ear but was ineffective when applied to the right ear. Ictal SPECT
      demonstrated right temporal hyperperfusion. MRI was normal. On high dose of
      carbamazepine, seizure frequency decreased. The addition of topiramate resulted
      in full seizure control. Musicogenic epilepsy is a rare form of reflex epilepsy.
      Pure cases, when patients do not experience unprovoked seizures, are exceptional.
      Our report confirms the implication of the right temporal lobe in this epilepsy.

PMID- 14684348
TI  - Children with Rolandic spikes and ictal vomiting: Rolandic epilepsy or
      Panayiotopoulos syndrome?
AB  - Centrotemporal spikes are the EEG marker of Rolandic epilepsy, while ictus
      emeticus is one of the main seizure manifestations of Panayiotopoulos syndrome.
      Ictus emeticus has not been reported in Rolandic epilepsy. Out of a population of
      1340 children with focal afebrile seizures we studied 24 children who had emetic
      manifestations in at least one seizure and centrotemporal spikes in at least one
      EEG. They were of normal neurological status and had a follow-up of at least two
      years after the last seizure. All children had sleep EEG following sleep
      deprivation. Two groups of patients were identified. Group A (12 patients) with
      EEG centrotemporal spikes only and group B (12 patients) with centrotemporal
      spikes and spikes in other locations. In 21 patients, ictal emetic manifestations
      culminated in vomiting and in three only nausea or retching occurred. The
      commonest presentation was ictus emeticus at onset followed by deviation of the
      eyes or staring, loss of contact and floppiness. In 79%, seizures occurred during
      sleep. Autonomic status epilepticus occurred in 37.5%. The mean age at onset was
      5.3 years. Overall analysis of the clinical and EEG data points out that the vast
      majority of these patients primarily suffer from Panayiotopoulos syndrome. Twenty
      patients (83%) had ictal semiology typical of Panayiotopoulos syndrome, but five
      also had concurrent Rolandic symptoms and four later developed pure Rolandic
      seizures. The other four patients (17%) had typical Rolandic seizures with
      concurrent ictus emeticus. These findings suggest a link between Rolandic
      epilepsy and Panayiotopoulos syndrome, the two most important phenotypes of the
      benign childhood seizure susceptibility syndrome.

PMID- 14684349
TI  - EEG characteristics in juvenile Huntington's disease: a case report and review of
      the literature.
AB  - The clinical features of Juvenile Huntington's Disease (J-HD) differ from those
      of the more common adult-onset form, and include cognitive decline, parkinsonism,
      myoclonus and seizures. A paucity of literature is available describing the
      electroencephalographic (EEG) findings. We describe the clinical and EEG
      characteristics of a patient with genetically confirmed J-HD. A review of
      previously published cases yielded EEG descriptions in only 23 patients whose
      disease onset was prior to the age of 32, and only 14 of these were prior to the
      age of 20. Epileptiform abnormalities were noted in 17 (74%), which was
      considerably more common than in the adult form. Generalized discharges were
      noted in nine, with six having polyspike and wave. The remainder had focal or
      multifocal epileptiform discharges. With genetic testing now available,
      refinement of the EEG data will be possible.

PMID- 14684350
TI  - Video-EEG evidence of lateralized clinical features in primary generalized
      epilepsy with tonic-clonic seizures.
AB  - BACKGROUND: Whether cortical or subcortical structures, specifically the
      thalamus, play the dominant role in generating primary generalized seizures has
      been the subject of long debate. Most experimental data implicate a
      hyperexcitable cortical generator of spike-and-wave activity, with the thalamus
      quickly recruited to sustain the generalized oscillations through a reverberating
      thalamocortical network. However, there is little clinical evidence to support
      the cortical generator hypothesis. We present video-EEG recordings of generalized
      tonic-clonic seizures in three patients with proven primary generalized epilepsy
      (PGE), all of whom showed a consistent pattern of lateralized seizure onset
      compatible with a focal frontal lobe generator. METHODS: Among 300 patients
      referred for video-EEG monitoring for intractable epilepsy, three were found to
      have PGE with tonic-clonic convulsions. All had a positive family history for
      epilepsy and no other epilepsy risk factors. Epilepsy onset was during
      adolescence (2/3) or childhood (1/3). Patients were taking 1-4 antiepileptic
      drugs (AEDs) at admission, none of which was valproic acid. RESULTS: Interictal
      EEG showed very active, bilaterally synchronous generalized spike-and-wave or
      polyspike-and-wave discharges between 2.5-4.5 Hz, maximal over the midfrontal
      structures symmetrically in all patients. Ictal EEG showed generalized rhythmic
      activity without lateralization at seizure onset. Surprisingly, in all 6 recorded
      tonic-clonic seizures there was a sustained (10-15 seconds), stereotyped,
      clinical lateralization at onset, which took the form of a tonic "fencing
      posture" in one patient (two seizures) and forced head/eye/torso version in two
      patients (four seizures). Two patients became seizure-free shortly after
      switching to valproate monotherapy. One patient refused valproate but has
      improved more than 90% with a change in AEDs to lamotrigine and phenobarbital
      (follow-up in all patients>18 months). CONCLUSIONS: Tonic-clonic seizures are
      presumed to be generalized from onset in patients with PGE. However, video-EEG
      monitoring in these patients is rarely performed and the actual clinical features
      of the seizures maybe underappreciated. The demonstration of sustained
      lateralization at onset in our patients, with features clinically
      indistinguishable from focal onset frontal lobe seizures, is compatible with the
      hypothesis of a focal region of cortical hyperexcitability situated in the
      frontal lobes of some patients with PGE. Whether this cortical generator is
      autonomous or "triggered" by ascending, possibly normal, thalamocortical volleys
      is unresolved.

PMID- 14684351
TI  - Adding topiramate to valproate therapy may cause reversible hepatic failure.
AB  - The authors report a 51-year-old women with pharmacoresistant partial epilepsy
      who tolerated well valproate monotherapy and in combination with several other
      antiepileptic drugs, but developed symptoms and signs of reversible hepatic
      failure under a combination of valproate and topiramate. Symptoms resolved after
      discontinuation of VPA. This case provides further anecdotal evidence that
      topiramate may increase the risk of liver failure when given in combination with
      other potentially hepatotoxic antiepileptic drugs.

PMID- 14684352
TI  - MRI evidence for the involvement of basal ganglia in epileptic seizures: an
      hypothesis.
AB  - Recent clinical and experimental studies have suggested that the basal ganglia
      are involved in epileptic seizures as a propagation pathway or as a remote
      inhibitory control circuit. The present case report may provide additional
      evidence from post-ictal magnetic resonance imaging (MRI) supporting this
      hypothesis. A healthy 13 year-old boy was admitted for a complex partial status
      epilepticus. MRI, performed one week later, revealed bilateral T2 hyperintense
      signals in the striata and a left temporal arachnoid cyst. Left temporal slow
      waves were noted on EEG recording. No obvious metabolic alterations were
      identified. During the next six years of follow-up, no seizure occurred and
      striatal alterations progressively disappeared. The clinical characteristics of
      the seizures, EEG slow waves, and probably the presence of an arachnoid cyst
      suggest that seizures originated from the left temporal lobe. The long-lasting
      MRI changes suggest that bilateral striatal alterations may have been secondary
      to an inflammatory process, which in turn could have disrupted a striatal
      inhibitory control over seizures. On the basis of these arguments, we speculate
      involvement of basal ganglia in epileptic seizures, as a part of a modulatory
      control system over seizures rather than a propagation pathway. Future reports
      will support or invalidate our hypothesis.

PMID- 14684353
TI  - Reflex epilepsy and non-ketotic hyperglycemia.
AB  - Epileptic seizures are paroxysmal events, and it is likely that many, if not
      most, of them are precipitated by known or unknown factors acting on a central
      nervous system that is predisposed to the production of epileptic discharges by
      the presence of an organic lesion, a genetically determined neuronal
      hyperexcitability, or both. Known precipitating influences are quite varied. We
      report the case of a 58 years-old patient, followed for non-ketotic
      hyperglycemia, who presented with focal seizures exclusively induced by specific,
      active or passive, postures and movements of the right arm or hand. MRI was
      normal. Following regulation of glucose blood levels the position-induced
      seizures stopped and antiepileptics were not prescribed. The seizures are kept
      under control by regulating blood glucose.

PMID- 14684355
TI  - Extracellular protease activation and unraveling of the myocardial interstitium:
      critical steps toward clinical applications.

PMID- 14684356
TI  - Function and regulation of mitochondrially produced nitric oxide in
      cardiomyocytes.

PMID- 14684357
TI  - Differing roles of mitochondrial nitric oxide synthase in cardiomyocytes and
      urothelial cells.
AB  - The existence of mitochondrial nitric oxide (NO) synthase (mtNOS) has been
      controversial since it was first reported in 1995. We have addressed this issue
      by making direct microsensor measurements of NO production in the mitochondria
      isolated from mouse hearts. Mitochondrial NO production was stimulated by Ca2+
      and inhibited by blocking electrogenic Ca2+ uptake or by using NOS antagonists.
      Cardiac mtNOS was identified as the neuronal isoform by the absence of NO
      production in the mitochondria of mice lacking the neuronal but not the
      endothelial or inducible isoforms. In cardiomyocytes from dystrophin-deficient
      (mdx) mice, elevated intracellular Ca2+, increased mitochondrial NO production,
      slower oxidative phosphorylation, and decreased ATP production were detected.
      Inhibition of mtNOS increased contractility in mdx but not in wild-type
      cardiomyocytes, indicating that mtNOS may protect the cells from overcontracting.
      mtNOS was also implicated in radiation-induced cell damage. In irradiated
      rat/mouse urinary bladders, we have evidence that mitochondrially produced NO
      damages the urothelial "umbrella" cells that line the bladder lumen. This damage
      disrupts the permeability barrier thereby creating the potential to develop
      radiation cystitis. RT-PCR and Southern blot analyses indicate that mtNOS is
      restricted to the umbrella cells, which scanning electron micrographs show are
      selectively damaged by radiation. Simultaneous microsensor measurements
      demonstrate that radiation increases NO and peroxynitrite (ONOO-) production in
      these cells, which can be prevented by transfection with manganese superoxide
      dismutase (MnSOD) or instillation of NOS antagonists during irradiation or
      irradiation of bladders devoid of mtNOS. These studies demonstrate that mtNOS is
      in the cardiomyocytes and urothelial cells, that it is derived from the neuronal
      isoform, and that it can be either protective or detrimental.

PMID- 14684358
TI  - Dynamics of protein nitration in cells and mitochondria.
AB  - Nitric oxide is a precursor of reactive nitrating species such as peroxynitrite
      and nitrogen dioxide that modify proteins to generate 3-nitrotyrosine. Many
      diseases are associated with increased levels of protein-bound nitrotyrosine, and
      this is used as a marker for oxidative damage. However, the regulation of protein
      nitration and its role in cell function are unclear. We demonstrate that
      biological protein nitration can be a specific and dynamic process. Proteins were
      nitrated in distinct temporal patterns in cells undergoing inflammatory
      activation, and protein denitration and renitration occurred rapidly in respiring
      mitochondria. The targets of protein nitration varied over time, which may
      reflect their sensitivity to nitration, expression pattern, or turnover. The
      dynamic nature of the nitration process was revealed by denitration and
      renitration of proteins occurring within minutes in mitochondria that were
      subject to hypoxiaanoxia and reoxygenation. Our results have implications that
      are particularly important for ischemia-reperfusion injury.

PMID- 14684359
TI  - A mitochondrial role for catabolism of nitric oxide in cardiomyocytes not
      involving oxymyoglobin.
AB  - The maximal concentration of nitric oxide (NO) developing in cultured cells
      following stimulation of endogenous NO synthases was shown to be submicromolar by
      NO-selective microelectrode measurements. In electron paramagnetic resonance
      experiments with isolated and finely divided pericardium, NO was found to react
      with oxymyoglobin to form metmyoglobin provided that NO was supplied at
      concentrations in excess of a few micromolar. However, at NO concentrations
      achievable by endogenous sources, this reaction did not take place to any
      measurable extent. Oxidative conversion of NO to nitrite ion by cytochrome c
      oxidase appears to be the most plausible route for cellular catabolism of NO.

PMID- 14684360
TI  - Cardioprotective effects of carvedilol on acute autoimmune myocarditis: anti
      inflammatory effects associated with antioxidant property.
AB  - Carvedilol, a new beta-blocker with antioxidant properties, has been shown to be
      cardioprotective in experimental models of myocardial damage. We investigated
      whether carvedilol protects against experimental autoimmune myocarditis (EAM)
      because of its suppression of inflammatory cytokines and its antioxidant
      properties. We orally administered a vehicle, various doses of carvedilol,
      racemic carvedilol [R(+)-carvedilol, an enantiomer of carvedilol without beta
      blocking activity], metoprolol, or propranolol to rats with EAM induced by
      porcine myosin for 3 wk. Echocardiographic study showed that the three beta
      blockers, except R(+)-carvedilol, suppressed left ventricular fractional
      shortening and decreased heart rates to the same extent. Carvedilol and R(+)
      carvedilol, but not metoprolol or propranolol, markedly reduced the severity of
      myocarditis at the two different doses and suppressed thickening of the left
      ventricular posterior wall in rats with EAM. Only carvedilol suppressed
      myocardial mRNA expression of inflammatory cytokines and IL-1beta protein
      expression in myocarditis. In addition, carvedilol and R(+)-carvedilol decreased
      myocardial protein carbonyl contents and myocardial thiobarbituric acid-reactive
      substance products in rats with EAM. The in vitro study showed that carvedilol
      and R(+)-carvedilol suppressed IL-1beta production in LPS-stimulated U937 cells
      and that carvedilol and R(+)-carvedilol, but not metoprolol or propranolol,
      suppressed thiobarbituric acid-reactive substance products in myocardial membrane
      challenged by oxidative stress. It was also confirmed that probucol, an
      antioxidant, ameliorated EAM in vivo. Carvedilol protects against acute EAM in
      rats, and the superior cardioprotective effect of carvedilol compared with
      metoprolol and propranolol may be due to suppression of inflammatory cytokines
      associated with the antioxidant properties in addition to the hemodynamic
      modifications.

PMID- 14684361
TI  - Involvement of calcitonin gene-related peptide in control of human fetoplacental
      vascular tone.
AB  - Calcitonin gene-related peptide (CGRP), one of the most potent endogenous
      vasodilators known, has been implicated in vascular adaptations and placental
      functions during pregnancy. The present study was designed to examine the
      existence of CGRP-A receptor components, the calcitonin receptor-like receptor
      (CRLR) and receptor activity-modifying protein 1 (RAMP1), in the human placenta
      and the vasoactivity of CGRP in the fetoplacental circulation. Immunofluorescent
      staining of the human placenta in term labor using polyclonal anti-CRLR and RAMP1
      antibodies revealed that labeling specifically concentrated in the vascular
      endothelium and the underlying smooth muscle cells in the umbilical artery/vein,
      chorionic artery/vein, and stem villous vessels as well as in the trophoblast
      layer of the placental villi. In vitro isometric force measurement showed that
      CGRP dose dependently relaxes the umbilical artery/vein, chorionic artery/vein,
      and stem villous vessels. Furthermore, CGRP-induced relaxation of placental
      vessels are inhibited by a CGRP receptor antagonist (CGRP8-37), ATP-sensitive
      potassium (KATP) channel blocker (glybenclamide), and cAMP-dependent protein
      kinase A inhibitor (Rp-cAMPS) and partially inhibited by a nitric oxide inhibitor
      (Nomega-nitro-l-arginine methyl ester). We propose that CGRP may play a role in
      the control of human fetoplacental vascular tone, and the vascular dilations in
      response to CGRP may involve activation of KATP channels, cAMP, and a nitric
      oxide pathway.

PMID- 14684362
TI  - Nitric oxide decreases the biological activity of norepinephrine resulting in
      altered vascular tone in the rat mesenteric arterial bed.
AB  - Nitric oxide (NO) reacts with catecholamines resulting in their deactivation. In
      this study, we demonstrated that coincubation of NO donors with sympathetic
      neurotransmitters decreased the amount of norepinephrine detected but not ATP or
      neuropeptide Y (NPY). Furthermore, we found that the ability of norepinephrine to
      increase perfusion pressure in the isolated perfused mesenteric arterial bed of
      the rat was attenuated by the incubation of norepinephrine with the NO donor
      diethylamine NONOate. Conversely, the vasoconstrictive ability of NPY and ATP was
      unaffected by incubation with NONOate. Periarterial nerve stimulation in the
      presence of the NO synthase (NOS) inhibitor Nomega-nitro-l-arginine methyl ester
      (l-NAME) resulted in an increase in both perfusion pressure response and
      norepinephrine levels. This was prevented by l-arginine, demonstrating that the
      effects of l-NAME were indeed specific to the inhibition of NOS. To confirm that
      NO was not altering the release of norepinephrine from the sympathetic nerve via
      presynaptic activation of guanylate cyclase, we repeated the experiments in the
      presence of the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]
      quinoxaloine-one (ODQ). Unlike l-NAME, ODQ infusion did not increase
      norepinephrine overflow, demonstrating that modulation of norepinephrine by NO at
      the vascular neuroeffector junction of the rat mesenteric vascular bed is not the
      result of presynaptic guanylate cyclase activation. These results demonstrate
      that, in addition to being a direct vasodilatator, NO can also alter vascular
      reactivity at the sympathetic neuroeffector junction in the rat mesenteric bed by
      deactivating the vasoconstrictor norepinephrine.

PMID- 14684363
TI  - Role of cGMP in carbon monoxide-induced cerebral vasodilation in piglets.
AB  - The hypothesis was addressed that CO-induced cerebral vasodilation requires a
      permissive cGMP signal that can be produced by nitric oxide (NO). Anesthetized
      piglets were implanted with cranial windows for measurement of pial arteriolar
      responses to stimuli. Pial arterioles dilated in response to isoproterenol (Iso),
      sodium nitroprusside (SNP), and CO or the CO-releasing molecule Mn2(CO)10
      [dimanganese decacarbonyl (DMDC)]. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one
      (ODQ), a soluble guanylyl cyclase inhibitor, decreased cerebrospinal fluid (CSF)
      cGMP and selectively inhibited dilations to SNP and DMDC without affecting the
      dilation to Iso. However, DMDC did not cause an increase in cortical
      periarachnoid CSF cGMP concentration. cGMP clamp with a threshold dilator level
      of 8-bromo-cGMP (10(-4) M) and ODQ restored the dilation to DMDC that had been
      blocked by ODQ alone. Under these conditions, cGMP was present but could not
      increase. Inhibition of the pial arteriolar dilation to glutamate by N-nitro-l
      arginine, which blocks NO synthase, was similar to that by heme oxygenase
      inhibitors, which block endogenous CO production. The dilation to glutamate,
      similar to dilation to DMDC, was partially restored by 8-bromo-cGMP and
      completely restored by SNP (5 x 10(-7) M). These data suggest that the permissive
      role of NO in CO- and glutamate-induced vasodilation involves maintaining the
      minimum necessary cellular level of cGMP to allow CO to cause dilation
      independently of increasing cGMP.

PMID- 14684364
TI  - Role of AIF in human coronary artery endothelial cell apoptosis.
AB  - Apoptosis-inducing factor (AIF), which exerts its effect via a caspase
      independent pathway, has been suggested to be a mediator of cell injury. We have
      recently identified the expression of AIF in human coronary artery endothelial
      cells (HCAECs). The present study was designed to determine the
      pathophysiological role of AIF in oxidized low-density lipoprotein (ox-LDL)
      induced apoptosis of HCAECs. The cells were cultured and treated with ox-LDL (40
      microg/ml) for 24 h. Ox-LDL increased AIF expression, caused apoptosis of HCAECs
      (determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling staining and large-scale DNA fragmentation), and induced translocation
      of AIF from the cytoplasm to the nucleus (fluorescence immunocytochemistry).
      Pretreatment of HCAECs with a caspase inhibitor (ZVAD-fmk) did not influence AIF
      mediated apoptosis in response to ox-LDL. We developed a specific antisense
      oligonucleotide targeted to the 5'-TCG CCG AAA TGT TCC GGT GTG GA-3' portion of
      the human AIF mRNA sequence (AIF-AS) to bind a complementary sequence overlapping
      the translational start site. Pretreatment of cells with the AIF-AS for 24 h
      resulted in suppression of ox-LDL-upregulated AIF protein, as measured by
      immunoblot analysis. AIF-AS also reduced apoptosis and AIF translocation (P <
      0.01 vs. ox-LDL alone). Next, we constructed a recombinant AIF plasmid by
      inserting whole-length AIF cDNA into the expression vector pcDNA3.1 with a
      cytomegalovirus promoter. HCAECs transfected with plasmid showed a two- to
      fourfold increase in AIF expression, extensive apoptosis, and translocation of
      AIF from the cytoplasm to the nucleus. These results from two approaches indicate
      that AIF plays an important role in ox-LDL-induced endothelial injury.

PMID- 14684365
TI  - Attenuation of I(K,slow1) and I(K,slow2) in Kv1/Kv2DN mice prolongs APD and QT
      intervals but does not suppress spontaneous or inducible arrhythmias.
AB  - Overexpression of a truncated Kv1.1 or Kv2.1 channel polypeptide in the heart
      (Kv1DN or Kv2DN) resulted in mice with a prolonged action potential duration
      (APD) due to marked attenuation of rapidly activating, slowly inactivating K+
      current (I(K,slow1)) or slowly inactivating outward K(+) current (I(K,slow2)) in
      ventricular myocytes. ECG monitoring, optical mapping, and programmed electrical
      stimulation of Kv1DN mice revealed spontaneous and inducible reentrant
      ventricular tachycardia due to spatial dispersion of repolarization and
      refractoriness. Recently, we demonstrated upregulation of I(K,slow2) in apical
      cardiomyocytes derived from Kv1DN mice. We therefore hypothesized that the
      selective upregulation of Kv2.1-encoded currents underlies the apex-to-base
      dispersion of repolarization and the reentrant arrhythmias. To test this
      hypothesis, the Kv1DN line was crossbred with the Kv2DN line to produce Kv1/Kv2DN
      lines. Whole cell voltage-clamp recordings from left ventricular cells of
      Kv1/Kv2DN confirmed that the 4-aminopyridine- and tetraethylammonium-sensitive
      components of IK,slow were eliminated, resulting in marked APD prolongation
      compared with wild-type, Kv1DN, and Kv2DN cells. Telemetric ECG recordings
      revealed prolongation of the corrected QT in Kv1/Kv2DN compared with Kv1DN and
      Kv2DN mice. However, attenuation of Kv2.1-encoded currents in Kv1DN mice did not
      suppress the arrhythmias. Thus, the elimination of I(K,slow2) prolongs APD and
      the QT intervals, but does not have an antiarrhythmic effect.

PMID- 14684366
TI  - Inhibition and reversal of myocardial infarction-induced hypertrophy and heart
      failure by NHE-1 inhibition.
AB  - Sodium/hydrogen exchange (NHE) inhibitors show promise as potential therapeutic
      agents for the treatment of heart failure, but it is not known whether they can
      reverse the maladaptive remodeling that results in heart failure. We sought to
      determine the effect of the NHE-1-specific inhibitor EMD-87580 (EMD) on heart
      failure produced by myocardial infarction in the rat and to assess whether up to
      4 wk of treatment delay results in beneficial effects. Male Sprague-Dawley rats
      were subjected to coronary artery ligation (or a sham procedure) and followed for
      up to 3 mo, at which time hypertrophy and hemodynamics were determined. EMD was
      provided in the diet, and treatment commenced immediately or 2-4 wk after
      ligation. EMD significantly reduced hemodynamic abnormalities, including the
      elevation in left ventricular end-diastolic pressure, and diminished the loss of
      systolic function with all treatment protocols. Left ventricular dilatation and
      hypertrophy, as assessed by heart weight, cell size, and atrial natriuretic
      peptide (ANP) expression, were similarly reversed to sham or near-sham levels. In
      addition, the increased plasma ANP and pro-ANP values were reversed to levels not
      significantly different from sham. Surprisingly, virtually all beneficial effects
      were identical with all treatment protocols. These effects were observed in the
      absence of infarct size reduction or blood pressure-lowering effects. Our results
      suggest that NHE-1 inhibition attenuates and reverses postinfarction remodeling
      and heart failure with a treatment delay of up to 4 wk after infarction. The
      effect is independent of infarct size or afterload reduction, indicating a direct
      effect on the myocardium.

PMID- 14684367
TI  - Estrogen suppresses IL-1beta-mediated induction of COX-2 pathway in rat cerebral
      blood vessels.
AB  - Interleukin (IL)-1beta is a potent inducer of inflammatory prostaglandins, which
      are important mediators of vascular response to cerebral injury, whereas estrogen
      reduces brain injury in models of ischemic stroke. Thus we examined the effects
      of in vivo IL-1beta exposure on cerebrovascular cyclooxygenase (COX)-2 expression
      and function in an animal model of chronic estrogen replacement. Estrogen-treated
      and nontreated ovariectomized female rats received IL-1beta injections (10
      microg/kg i.p.), and then cerebral vessels were isolated for biochemical and
      contractile measurements. In estrogen-deficient rats, IL-1beta induced
      cerebrovascular COX-2 protein expression; a peak response occurred 3 h after
      injection. COX-2 was localized to arterial endothelium using confocal microscopy.
      IL-1beta increased PGE2 but not PGI2 production and decreased vascular tone as
      measured in isolated cerebral arteries; the latter effect was partially reversed
      by treatment with the selective COX-2 inhibitor NS-398 (10 micromol/l). In
      contrast, in animals treated with estrogen, IL-1beta had no significant effect on
      COX-2 protein levels, PGE2 production, or vascular tone. Combined treatment with
      17beta-estradiol and medroxyprogesterone acetate also prevented increases in PGE2
      production after IL-1beta treatment, but treatment with 17alpha-estradiol had no
      effect. IL-1beta induction of COX-2 protein was prevented by treatment with the
      nuclear factor-kappaB inhibitor caffeic acid phenethyl ester (20 mg/kg i.p.), and
      estrogen treatment reduced cerebrovascular nuclear factor-kappaB activity.
      Estrogen thus has potent anti-inflammatory effects with respect to cerebral
      vascular responses to IL-1beta. These effects may have important implications for
      the incidence and severity of cerebrovascular disease.

PMID- 14684368
TI  - Right ventricular adaptation to pulmonary hypertension: an interspecies
      comparison.
AB  - Right ventricular (RV) adaptation is an important prognostic factor in acute and
      chronic pulmonary hypertension. Pulmonary vascular basal tone and hypoxic
      reactivity are known to vary widely between species. We investigated how RV
      adaptation to acute pulmonary hypertension is preserved in species with low,
      intermediate, and high pulmonary vascular resistance and reactivity. Acute
      pulmonary hypertension was induced by hypoxia, distal embolism, and proximal
      constriction in anesthetized dogs (n = 10), goats (n = 8), and pigs (n = 8).
      Pulmonary vessels were assessed by flow-pressure curves and by impedance to
      quantify distal resistance, proximal elastance, and wave reflections. RV function
      was assessed by pressure-volume curves to quantify afterload, contractility, and
      ventricular-arterial coupling efficiency. First, hypoxia was associated with a
      progressive increase of resistance, elastance, and wave reflection from dogs to
      goats and from goats to pigs. RV contractility increased proportionally to RV
      afterload, and optimal coupling was preserved in all species. Second, embolism
      increased resistance and wave reflection but not elastance. The increase in RV
      contractility matched the increase in RV afterload and optimal coupling was
      preserved. Finally, proximal pulmonary artery constriction increased resistance,
      increased and accelerated wave reflection, and markedly increased elastance. RV
      contractility increased markedly and coupling showed a nonsignificant trend to
      decrease. We conclude that optimal or near-optimal ventricular-arterial coupling
      is maintained in acute pulmonary hypertension, whether in absence or presence of
      chronic species-induced pulmonary hypertension.

PMID- 14684369
TI  - Central angiotensin II-induced pressor responses and neural activity in utero and
      hypothalamic angiotensin receptors in preterm ovine fetus.
AB  - The central renin-angiotensin system is important in the control of blood
      pressure in the adult. However, few data exist about the in utero development of
      central angiotensin-mediated pressor responses. Our recent studies have shown
      that the application of ANG II into the fetal brain can increase blood pressure
      at near term. The present study determined fetal blood pressure and heart rate in
      response to a central application of ANG II in the chronically prepared preterm
      ovine fetus, determined the action sites marked by c-Fos expression in the fetal
      central pathways after intracerebroventricular injection of ANG II in utero, and
      determined angiotensin subtype 1 receptors in the fetal hypothalamus. Central
      injection of ANG II significantly increased fetal mean arterial pressure (MAP).
      Adjusted fetal MAP against amniotic pressure was also increased by ANG II. Fetal
      heart rate was subsequently decreased after the central administration of ANG II
      and/or the increase of blood pressure. ANG II induced c-Fos expression in the
      central putative cardiovascular area, the paraventricular nuclei in the brain
      sympathetic pathway. Application of ANG II also caused intense Fos
      immunoreactivity in the tractus solitarius nuclei in the hindbrain. In addition,
      intense angiotensin subtype 1 receptors were expressed in the hypothalamus at
      preterm. These data demonstrate that central ANG II-related pressor centers start
      to function as early as at preterm and suggest that the central angiotensin
      related sympathetic pathway is likely intact in the control of blood pressure in
      utero.

PMID- 14684370
TI  - Myocardial ischemia induces the release of substance P from cardiac afferent
      neurons in rat thoracic spinal cord.
AB  - Antibody-coated microprobes were inserted into the thoracic (T3-4) spinal cord in
      urethane-anesthetized Sprague-Dawley rats to detect the differences in the
      release of immunoreactive substance P-like (irSP) substances in response to
      differential activation of cardiac nociceptive sensory neurons (CNAN). CNAN were
      stimulated either by intrapericardial infusion of an inflammatory ischemic
      exudate solution (IES) containing algogenic substances (i.e., 10 mM each of
      adenosine, bradykinin, prostaglandin E2, and 5-hydroxytryptamine), or by
      transient occlusion of the left anterior descending coronary artery (CoAO). There
      was widespread basal release of irSP from the thoracic spinal cord. Stimulation
      of the CNAN by IES did not alter the pattern of release of irSP. Conversely, CoAO
      augmented the release of irSP from T3-4 spinal segments from laminae I-VII. This
      CoAO-induced irSP release was eliminated after thoracic dorsal rhizotomy. These
      results indicate that heterogeneous activation of cardiac afferents, as with
      focal coronary artery occlusion, represents an optimum input for activation of
      the cardiac neuronal hierarchy and for the resultant perception of angina.
      Excessive stimulation of cardiac nociceptive afferent neurons elicited during
      regional coronary artery occlusion involves the release of SP in the thoracic
      spinal cord and suggests that local spinal cord release of SP may be involved in
      the neural signaling of angina.

PMID- 14684371
TI  - Effects of phospholemman downregulation on contractility and [Ca(2+)]i transients
      in adult rat cardiac myocytes.
AB  - Phospholemman (PLM) expression was increased in rat hearts after myocardial
      infarction (MI). Overexpression of PLM in normal adult rat cardiac myocytes
      altered contractile function and cytosolic Ca(2+) concentration ([Ca(2+)](i))
      homeostasis in a manner similar to that observed in post-MI myocytes. In this
      study, we tested whether PLM downregulation in normal adult rat myocytes resulted
      in contractility and [Ca(2+)](i) transient changes opposite to those observed in
      post-MI myocytes. Compared with control myocytes infected with adenovirus (Adv)
      expressing green fluorescent protein (GFP) alone, myocytes infected with Adv
      expressing both GFP and rat antisense PLM (rASPLM) had 23% less PLM protein (P <
      0.012) at 3 days, but no differences were found in sarcoplasmic reticulum (SR)
      Ca(2+)-ATPase, Na(+)/Ca(2+) exchanger (NCX1), Na(+)-K(+)-ATPase, and
      calsequestrin levels. SR Ca(2+) uptake and whole cell capacitance were not
      affected by rASPLM treatment. Relaxation from caffeine-induced contracture was
      faster, and NCX1 current amplitudes were higher in rASPLM myocytes, indicating
      that PLM downregulation enhanced NCX1 activity. In native rat cardiac myocytes,
      coimmunoprecipitation experiments indicated an association of PLM with NCX1. At
      0.6 mM [Ca(2+)](o), rASPLM myocytes had significantly (P < 0.003) lower
      contraction and [Ca(2+)](i) transient amplitudes than control GFP myocytes. At 5
      mM [Ca(2+)](o), both contraction and [Ca(2+)](i) transient amplitudes were higher
      in rASPLM myocytes. This pattern of contractile and [Ca(2+)](i) transient
      behavior in rASPLM myocytes was opposite to that observed in post-MI rat
      myocytes. We conclude that downregulation of PLM in normal rat cardiac myocytes
      enhanced NCX1 function and affected [Ca(2+)](i) transient and contraction
      amplitudes. We suggest that PLM downregulation offers a potential therapeutic
      strategy for ameliorating contractile abnormalities in MI myocytes.

PMID- 14684372
TI  - Effect of fitness on arm vascular and metabolic responses to upper body exercise.
AB  - We investigated arm perfusion and metabolism during upper body exercise. Eight
      average, fit subjects and seven rowers, mean +/- SE maximal oxygen uptake (VO2
      max) 157 +/- 7 and 223 +/- 14 ml O2. kg(-0.73).min(-1), respectively, performed
      incremental arm cranking to exhaustion. Arm blood flow (ABF) was measured with
      thermodilution and arm muscle mass was estimated by dual-energy X-ray
      absorptiometry. During maximal arm cranking, pulmonary VO2 was approximately 45%
      higher in the rowers compared with the untrained subjects and peak ABF was 6.44
      +/- 0.40 and 4.55 +/- 0.26 l/min, respectively (P < 0.05). The arm muscle mass
      for the rowers and the untrained subjects was 3.5 +/- 0.4 and 3.3 +/- 0.1 kg,
      i.e., arm perfusion was 1.9 +/- 0.2 and 1.4 +/- 0.1 l blood.kg(-1).min(-1),
      respectively (P < 0.05). The arteriovenous O2 difference was 156 +/- 7 and 120 +/
      8 ml/l, respectively, and arm VO2 was 0.98 +/- 0.08 and 0.60 +/- 0.04 l/min
      corresponding with 281 +/- 22 and 181 +/- 12 ml/kg, while arm O(2) diffusional
      conductance was 49.9 +/- 4.3 and 18.6 +/- 3.2 ml.min(-1).mmHg(-1), respectively
      (P < 0.05). Also, lactate release in the rowers was almost three times higher
      than in the untrained subjects (26.4 +/- 1.1 vs. 9.5 +/- 0.4 mmol/min, P < 0.05).
      The energy requirement of an approximately 50% larger arm work capacity after
      long-term arm endurance training is covered by an approximately 60% increase in
      aerobic metabolism and an almost tripling of the anaerobic capacity.

PMID- 14684373
TI  - Nicorandil induces late preconditioning against myocardial infarction in
      conscious rabbits.
AB  - Nicorandil has been shown to induce an infarct-limiting effect similar to that
      induced by the early phase of ischemic preconditioning (PC). The goals of this
      study were to determine whether nicorandil induces a delayed cardioprotection
      that is analogous to the late phase of ischemic PC and, if so, whether nicorandil
      induced late PC is associated with upregulation of cardioprotective proteins.
      Chronically instrumented, conscious rabbits received vehicle (intravenous normal
      saline; control group, n = 10), nicorandil (100 microg/kg bolus + 30 microg x kg(
      1) x min(-1) i.v. for 60 min; nicorandil group, n = 10), or ischemic PC (6 cycles
      of 4-min coronary occlusion/4-min reperfusion; PC group, n = 8). Twenty-four
      hours later, rabbits underwent a 30-min coronary occlusion, followed by 3 days of
      reperfusion. Myocardial infarct size was significantly reduced in rabbits
      pretreated with nicorandil (27.5 +/- 5.3% of the risk region) or with ischemia
      (30.3 +/- 4.2%) versus controls (59.1 +/- 4.7%, P < 0.05 vs. both). Furthermore,
      the expression of cyclooxygenase-2 (COX-2) and Bcl-2 was significantly elevated
      (+38% and +126%, respectively; P < 0.05) in myocardium of rabbits given
      nicorandil 24 h earlier versus controls. We conclude that nicorandil induces
      delayed cardioprotection against myocardial infarction similar to that afforded
      by the late phase of ischemic PC, possibly by upregulating COX-2 and Bcl-2.

PMID- 14684374
TI  - Coupling of angiotensin II AT1 receptors to neuronal NHE activity and carrier
      mediated norepinephrine release in myocardial ischemia.
AB  - In ischemia, cardiac sympathetic nerve endings (cSNE) release excessive amounts
      of norepinephrine (NE) via the nonexocytotic Na(+)-dependent NE transporter
      (NET). NET, normally responsible for NE reuptake into cSNE, reverses in
      myocardial ischemia, releasing pathological amounts of NE. This carrier-mediated
      NE release can be triggered by elevated intracellular Na(+) levels in the
      axoplasm. The fact that ischemia activates the intracellular pH regulatory
      Na(+)/H(+) exchanger (NHE) in cSNE is pivotal in increasing intraneuronal Na(+)
      and thus activating carrier-mediated NE release. Angiotensin (ANG) II levels are
      also significantly elevated in the ischemic heart. However, the effects of ANG II
      on cSNE, which express the ANG II receptor, AT(1)R, are poorly understood. We
      hypothesized that ANG II-induced AT(1)R activation in cSNE may be positively
      coupled to NHE activity and thereby facilitate the pathological release of NE
      associated with myocardial ischemia. We tested this hypothesis in a cSNE model,
      human neuroblastoma cells stably transfected with rat recombinant AT(1A) receptor
      (SH-SY5Y-AT(1A)). SH-SY5Y-AT(1A) constitutively expresses amiloride-sensitive NHE
      and the NET. NHE activity was assayed in BCECF-loaded SH-SY5Y-AT(1A) as the rate
      of the Na(+)-dependent alkalinization in response to an acute acidosis. ANG II
      activation of AT(1)R markedly increased NHE activity in SH-SY5Y-AT(1A) via a
      Ca(2+)-dependent pathway and promoted carrier-mediated NE release. In addition,
      in guinea pig cSNE expressing native AT(1)R, ANG II elicited carrier-mediated NE
      release. In SH-SY5Y-AT(1A) and cSNE, amiloride inhibited the ANG II-mediated
      release of NE. Our results provide a link between AT(1)R and NHE in cSNE, which
      can exacerbate carrier-mediated NE release during protracted myocardial ischemia.

PMID- 14684375
TI  - Aging attenuates vascular and metabolic plasticity but does not limit improvement
      in muscle VO(2) max.
AB  - The interactions between exercise, vascular and metabolic plasticity, and aging
      have provided insight into the prevention and restoration of declining whole body
      and small muscle mass exercise performance known to occur with age. Metabolic and
      vascular adaptations to normoxic knee-extensor exercise training (1 h 3 times a
      week for 8 wk) were compared between six sedentary young (20 +/- 1 yr) and six
      sedentary old (67 +/- 2 yr) subjects. Arterial and venous blood samples, in
      conjunction with a thermodilution technique facilitated the measurement of
      quadriceps muscle blood flow and hematologic variables during incremental knee
      extensor exercise. Pretraining, young and old subjects attained a similar maximal
      work rate (WR(max)) (young = 27 +/- 3, old = 24 +/- 4 W) and similar maximal
      quadriceps O(2) consumption (muscle Vo(2 max)) (young = 0.52 +/- 0.03, old = 0.42
      +/- 0.05 l/min), which increased equally in both groups posttraining (WR(max),
      young = 38 +/- 1, old = 36 +/- 4 W, Muscle Vo(2 max), young = 0.71 +/- 0.1, old =
      0.63 +/- 0.1 l/min). Before training, muscle blood flow was approximately 500 ml
      lower in the old compared with the young throughout incremental knee-extensor
      exercise. After 8 wk of knee-extensor exercise training, the young reduced muscle
      blood flow approximately 700 ml/min, elevated arteriovenous O(2) difference
      approximately 1.3 ml/dl, and increased leg vascular resistance approximately 17
      mmHg x ml(-1) x min(-1), whereas the old subjects revealed no training-induced
      changes in these variables. Together, these findings indicate that after 8 wk of
      small muscle mass exercise training, young and old subjects of equal initial
      metabolic capacity have a similar ability to increase quadriceps muscle WR(max)
      and muscle Vo(2 max), despite an attenuated vascular and/or metabolic adaptation
      to submaximal exercise in the old.

PMID- 14684376
TI  - Effects of left ventricular contractility and coronary vascular resistance on
      coronary dynamics.
AB  - Wave-intensity analysis, which separates upstream from downstream events and
      defines their interaction, has been used to study the effects of changes in left
      ventricular (LV) contractility (E(max)) and left circumflex coronary artery
      resistance (R(LCx)) on the coronary systolic flow impediment (CSFI). In 10
      anesthetized, open-chest dogs, we measured coronary, aortic, and LV pressures,
      coronary velocity (Flowire), and flow. E(max) was increased by paired pacing and
      R(LCx) was modulated by intracoronary infusions of vasodilators (adenosine and
      nitroglycerin) and a vasoconstrictor (phenylephrine). When both E(max) and R(LCx)
      were varied, CSFI and the energy of the backward-going compression wave (I(W-))
      were greatest at the highest levels of E(max) and the lowest levels of R(LCx).
      I(W-) was proportional to the CSFI. We conclude that contractility and coronary
      resistance change CSFI by modulating the backward-going compression wave.

PMID- 14684377
TI  - SDF-1/CXCL12 regulates cAMP production and ion transport in intestinal epithelial
      cells via CXCR4.
AB  - Human colonic epithelial cells express CXCR4, the sole cognate receptor for the
      chemokine stromal cell-derived factor (SDF)-1/CXC chemokine ligand (CXCL) 12. The
      aim of this study was to define the mechanism and functional consequences of
      signaling intestinal epithelial cells through the CXCR4 chemokine receptor.
      CXCR4, but not SDF-1/CXCL12, was constitutively expressed by T84, HT-29, HT-29/
      18C1, and Caco-2 human colon epithelial cell lines. Studies using T84 cells
      showed that CXCR4 was G protein-coupled in intestinal epithelial cells. Moreover,
      stimulation of T84 cells with SDF-1/CXCL12 inhibited cAMP production in response
      to the adenylyl cyclase activator forskolin, and this inhibition was abrogated by
      either anti-CXCR4 antibody or receptor desensitization. Studies with pertussis
      toxin suggested that SDF-1/CXCL12 activated negative regulation of cAMP
      production through G(i)alpha subunits coupled to CXCR4. Consistent with the
      inhibition of forskolin-stimulated cAMP production, SDF-1/CXCL12 also inhibited
      forskolin-induced ion transport in voltage-clamped polarized T84 cells. Taken
      together, these data indicate that epithelial CXCR4 can transduce functional
      signals in human intestinal epithelial cells that modulate important cAMP
      mediated cellular functions.

PMID- 14684378
TI  - Mitochondrial autophagy and injury in the liver in alpha 1-antitrypsin
      deficiency.
AB  - Homozygous, PIZZ alpha(1)-antitrypsin (alpha(1)-AT) deficiency is associated with
      chronic liver disease and hepatocellular carcinoma resulting from the toxic
      effects of mutant alpha(1)-anti-trypsin Z (alpha(1)-ATZ) protein retained in the
      endoplasmic reticulum (ER) of hepatocytes. However, the exact mechanism(s) by
      which retention of this aggregated mutant protein leads to cellular injury are
      still unknown. Previous studies have shown that retention of mutant alpha(1)-ATZ
      in the ER induces an intense autophagic response in hepatocytes. In this study,
      we present evidence that the autophagic response induced by ER retention of
      alpha(1)-ATZ also involves the mitochondria, with specific patterns of both
      mitochondrial autophagy and mitochondrial injury seen in cell culture models of
      alpha(1)-AT deficiency, in PiZ transgenic mouse liver, and in liver from alpha(1)
      AT-deficient patients. Evidence for a unique pattern of caspase activation was
      also detected. Administration of cyclosporin A, an inhibitor of mitochondrial
      permeability transition, to PiZ mice was associated with a reduction in
      mitochondrial autophagy and injury and reduced mortality during experimental
      stress. These results provide evidence for the novel concept that mitochondrial
      damage and caspase activation play a role in the mechanism of liver cell injury
      in alpha(1)-AT deficiency and suggest the possibility of mechanism-based
      therapeutic interventions.

PMID- 14684379
TI  - Gastric distension-induced release of 5-HT stimulates c-fos expression in
      specific brain nuclei via 5-HT3 receptors in conscious rats.
AB  - We examined c-fos expression in specific brain nuclei in response to gastric
      distension and investigated whether 5-HT released from enterochromaffin (EC)
      cells was involved in this response. The role of 5-HT3 receptors in this
      mechanism was also addressed. Release of 5-HT was examined in an ex vivo-perfused
      stomach model, whereas c-fos expression in brain nuclei induced by gastric
      distension was examined in a freely moving conscious rat model. Physiological
      levels of gastric distension stimulated the vascular release of 5-HT more than
      luminal release of 5-HT, and induced c-fos expression in the nucleus of the
      solitary tract (NTS), area postrema (AP), paraventricular nucleus (PVN), and
      supraoptic nucleus (SON). The c-fos expression in all these brain nuclei was
      blocked by truncal vagotomy as well as by perivagal capsaicin treatment,
      suggesting that vagal afferent pathways may mediate this response. Intravenous
      injection of 5-HT3 receptor antagonist granisetron blocked c-fos expression in
      all brain nuclei examined, although intracerebroventricular injection of
      granisetron had no effect, suggesting that 5-HT released from the stomach may
      activate 5-HT3 receptors located in the peripheral vagal afferent nerve terminals
      and then induce brain c-fos expression. c-fos Positive cells in the NTS were
      labeled with retrograde tracer fluorogold injected in the PVN, suggesting that
      neurons in the NTS activated by gastric distension project axons to the PVN. The
      present results suggest that gastric distension stimulates 5-HT release from the
      EC cells and the released 5-HT may activate 5-HT3 receptors located on the vagal
      afferent nerve terminals in the gastric wall leading to neuron activation in the
      NTS and AP and subsequent activation of neurons in the PVN and SON.

PMID- 14684380
TI  - Dietary cholesterol stimulates CYP7A1 in rats because farnesoid X receptor is not
      activated.
AB  - Cholesterol feeding upregulates CYP7A1 in rats but downregulates CYP7A1 in
      rabbits. To clarify the mechanism responsible for the upregulation of CYP7A1 in
      cholesterol-fed rats, the effects of dietary cholesterol (Ch) and cholic acid
      (CA) on the activation of the nuclear receptors, liver X-receptor (LXR-alpha) and
      farsenoid X-receptor (FXR), which positively and negatively regulate CYP7A1, were
      investigated in rats. Studies were carried out in four groups (n = 12/group) of
      male Sprague-Dawley rats fed regular chow (control), 2% Ch, 2% Ch + 1% CA, and 1%
      CA alone for 1 wk. Changes in mRNA expression of short heterodimer partner (SHP)
      and bile salt export pump (BSEP), target genes for FXR, were determined to
      indicate FXR activation, whereas the expression of ABCA1 and lipoprotein lipase
      (LPL), target genes for LXR-alpha, reflected activation. CYP7A1 mRNA and activity
      increased twofold and 70%, respectively, in rats fed Ch alone when the bile acid
      pool size was stable but decreased 43 and 49%, respectively, after CA was added
      to the Ch diet, which expanded the bile acid pool 3.4-fold. SHP and BSEP mRNA
      levels did not change after feeding Ch but increased 88 and 37% in rats fed Ch +
      CA. This indicated that FXR was activated by the expanded bile acid pool. When Ch
      or Ch + CA were fed, hepatic concentrations of oxysterols, ligands for LXR-alpha
      increased to activate LXR-alpha, as evidenced by increased mRNA levels of ABCA1
      and LPL. Feeding CA alone enlarged the bile acid pool threefold and increased the
      expression of both SHP and BSEP. These results suggest that LXR-alpha was
      activated in rats fed both Ch or Ch + CA, whereas CYP7A1 mRNA and activity were
      induced only in Ch-fed rats where the bile acid pool was not enlarged such that
      FXR was not activated. In rats fed Ch + CA, the bile acid pool expanded, which
      activated FXR to offset the stimulatory effects of LXR-alpha on CYP7A1.

PMID- 14684381
TI  - Calcineurin mediates pancreatic growth in protease inhibitor-treated mice.
AB  - CCK acts on pancreatic acinar cells to increase intracellular Ca(2+) leading to
      secretion of digestive enzymes and, in the long term, pancreatic growth.
      Calcineurin (CN) is a serine/threonine-specific protein phosphatase activated by
      Ca(2+) and calmodulin that recently has been shown to participate in the growth
      regulation of cardiac and skeletal myocytes. We therefore tested the effect of
      two different CN inhibitors, cyclosporine A (CsA) and FK506, on mouse pancreatic
      growth induced by oral administration of the synthetic protease inhibitor
      camostat, a known stimulator of endogenous CCK release. Mice were fed a powdered
      diet with or without 0.1% camostat. Pancreatic wet weight, protein, and DNA were
      increased in response to camostat in a time-dependent manner over 10 days in ICR
      mice but not in CCK-deficient mice. Both CsA (15 mg/kg) and FK506 (3 mg/kg) given
      twice daily blocked the increase in pancreatic wet weight and protein and DNA
      content induced by camostat. The increase in plasma CCK induced by camostat was
      not blocked by CsA or FK506. Camostat feeding also increased the relative amount
      of CN protein, whereas levels of MAPKs, ERKs, and p38 were not altered. In
      summary, 1) CCK released by chronic camostat feeding induces pancreatic growth in
      mice; 2) this growth is blocked by treatment with both CsA and FK506, indicating
      a role for CN; 3) CCK stimulation also increases CN protein. In conclusion,
      activation and possibly upregulation of CN may participate in regulation of
      pancreatic growth by CCK in mice.

PMID- 14684382
TI  - A voltage-gated K(+) current in renal inner medullary collecting duct cells.
AB  - We studied the K(+)-selective conductances in primary cultures of rat renal inner
      medullary collecting duct (IMCD) using perforated-patch and conventional whole
      cell techniques. Depolarizations above -20 mV induced a time-dependent outward
      K(+) current (I(vto)) similar to a delayed rectifier. I(vto) showed a half
      maximal activation around 5.6 mV with a slope factor of 6.8 mV. Its K(+)/Na(+)
      selectivity ratio was 11.7. It was inhibited by tetraethylammonium, quinidine, 4
      aminopyridine, and Ba(2+) and was not Ca(2+) dependent. The delayed rectifying
      characteristics of I(vto) prompted us to screen the expression of Kv1 and Kv3
      families by RT-PCR. Analysis of RNA isolated from cell cultures revealed the
      presence of three Kv alpha-subunits (Kv1.1, Kv1.3, and Kv1.6). Western blot
      analysis with Kv alpha-subunit antibodies for Kv1.1 and Kv1.3 showed labeling of
      approximately 70-kDa proteins from inner medulla plasmatic and microsome
      membranes. Immunocytochemical analysis of cell culture and kidney inner medulla
      showed that Kv1.3 is colocalized with the Na(+)-K(+)-ATPase at the basolateral
      membrane, although it is also in the cytoplasm. This is the first evidence of
      recording, protein expression, and localization of a voltage-gated Kv1 in the
      kidney IMCD cells.

PMID- 14684384
TI  - Differential expression and targeting of endogenous Arf1 and Arf6 small GTPases
      in kidney epithelial cells in situ.
AB  - ADP-ribosylation factors (Arfs) are small GTPases that regulate vesicular
      trafficking in exo- and endocytotic pathways. As a first step in understanding
      the role of Arfs in renal physiology, immunocytochemistry and Western blotting
      were performed to characterize the expression and targeting of Arf1 and Arf6 in
      epithelial cells in situ. Arf1 and Arf6 were associated with apical membranes and
      subapical vesicles in proximal tubules, where they colocalized with megalin. Arf1
      was also apically expressed in the distal tubule, connecting segment, and
      collecting duct (CD). Arf1 was abundant in intercalated cells (IC) and
      colocalized with V-ATPase in A-IC (apical) and B-IC (apical and/or basolateral).
      In contrast, Arf6 was associated exclusively with basolateral membranes and
      vesicles in the CD. In the medulla, basolateral Arf6 was detectable mainly in A
      IC. Expression in principal cells became weaker throughout the outer medulla, and
      Arf6 was not detectable in principal cells in the inner medulla. In some kidney
      epithelial cells Arf1 but not Arf6 was also targeted to a perinuclear patch,
      where it colocalized with TGN38, a marker of the trans-Golgi network.
      Quantitative Western blotting showed that expression of endogenous Arf1 was 26
      180 times higher than Arf6. These data indicate that Arf GTPases are expressed
      and targeted in a cell- and membrane-specific pattern in kidney epithelial cells
      in situ. The results provide a framework on which to base and interpret future
      studies on the role of Arf GTPases in the multitude of cellular trafficking
      events that occur in renal tubular epithelial cells.

PMID- 14684387
TI  - Evidence for nucleotide receptor modulation of cross talk between MAP kinase and
      NF-kappa B signaling pathways in murine RAW 264.7 macrophages.
AB  - Extracellular nucleotides such as ATP are present in abundance at sites of
      inflammation and tissue damage, and these agents exert a potent modulatory effect
      on macrophage/monocyte function via the nucleotide receptor P2X(7). In this
      regard, after exposure to bacterial LPS, P2X(7) activation augments expression of
      the inducible nitric oxide (NO) synthase and production of NO in macrophages.
      Because P2X(7) has been reported to stimulate certain members of the MAP kinase
      family (ERK1/2) and can enhance the DNA-binding activity of NF-kappa B, we tested
      the hypothesis that LPS and nucleotides regulate NF-kappa B-dependent
      inflammatory events via cross talk with MAPK-associated pathways. In this regard,
      the present studies revealed that cotreatment of macrophages with LPS and the
      P2X(7)-selective ligand 2'-3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate
      (BzATP) results in the cooperative activation of NF-kappa B DNA-binding activity
      and a sustained attenuation of levels of the NF-kappa B inhibitory protein I
      kappa B alpha. Interestingly, a persistent reduction in I kappa B alpha levels is
      also observed when the MEK1/2 inhibitor U0126 is coadministered with LPS,
      suggesting that components of the MEK/ERK pathway are involved in regulating I
      kappa B alpha protein expression and/or turnover. The observation that U0126 and
      BzATP exhibit overlapping actions with respect to LPS-induced changes in I kappa
      B alpha levels is supported by the finding that Ras activation, which is upstream
      of MEK/ERK activation, is reduced upon macrophage cotreatment with BzATP and LPS
      compared with the effects of BzATP treatment alone. These data are consistent
      with the concept that the Ras/MEK/ERK pathways are involved in regulating NF
      kappa B/I kappa B-dependent inflammatory mediator production and suggest a
      previously unidentified mechanism by which nucleotides can modulate LPS-induced
      action via cross talk between NF-kappa B and Ras/MEK/MAPK-associated pathways.

PMID- 14684389
TI  - Intramuscular administration of iron dextran is inappropriate for treatment of
      moderate pregnancy anemia, both in intervention research on underprivileged women
      and in routine prenatal care provided by public health services.

PMID- 14684390
TI  - Diet for the heart or the bone: a biological tradeoff.

PMID- 14684391
TI  - Poverty and obesity: the role of energy density and energy costs.
AB  - Many health disparities in the United States are linked to inequalities in
      education and income. This review focuses on the relation between obesity and
      diet quality, dietary energy density, and energy costs. Evidence is provided to
      support the following points. First, the highest rates of obesity occur among
      population groups with the highest poverty rates and the least education. Second,
      there is an inverse relation between energy density (MJ/kg) and energy cost (US
      dollars/MJ), such that energy-dense foods composed of refined grains, added
      sugars, or fats may represent the lowest-cost option to the consumer. Third, the
      high energy density and palatability of sweets and fats are associated with
      higher energy intakes, at least in clinical and laboratory studies. Fourth,
      poverty and food insecurity are associated with lower food expenditures, low
      fruit and vegetable consumption, and lower-quality diets. A reduction in diet
      costs in linear programming models leads to high-fat, energy-dense diets that are
      similar in composition to those consumed by low-income groups. Such diets are
      more affordable than are prudent diets based on lean meats, fish, fresh
      vegetables, and fruit. The association between poverty and obesity may be
      mediated, in part, by the low cost of energy-dense foods and may be reinforced by
      the high palatability of sugar and fat. This economic framework provides an
      explanation for the observed links between socioeconomic variables and obesity
      when taste, dietary energy density, and diet costs are used as intervening
      variables. More and more Americans are becoming overweight and obese while
      consuming more added sugars and fats and spending a lower percentage of their
      disposable income on food.

PMID- 14684392
TI  - Nutrition and low birth weight: from research to practice.
AB  - Low birth weight (LBW) remains a significant public health problem in many
      developing countries, and poor nutrition both before and during pregnancy is
      recognized as an important cause. Emerging evidence on the role of
      intergenerational effects in determining maternal preconceptual nutritional
      status indicates the need for continued investment in strategies that improve
      women's nutrition and health throughout the life cycle, especially during the
      early years. Controlled trials have shown that improving food intakes during
      pregnancy effectively reduces LBW, but programs have been less successful because
      these interventions are expensive and difficult to manage. Multivitamin-mineral
      supplements have been viewed as a simpler solution, but 2 of 3 controlled trials
      conducted to date failed to show that multivitamin-mineral supplements are more
      effective than are iron-folate supplements, which are already the standard of
      care during pregnancy. Emerging evidence indicating the benefits of iron
      supplements in improving birth weight illustrate the need for increased efforts
      to reduce iron deficiency by improving coverage of antenatal programs and
      promoting fortification. Other causes of LBW include environmental factors, such
      as smoking; indoor air pollution; and infections, such as malaria. However,
      little is known about the interactions between nutrition and infection.
      Underlying social factors, such as poverty and women's status, are also
      important, especially in South Asia, where more than one-half of the world's LBW
      infants are born. In summary, strategies that combine nutrition-based
      interventions, such as improving food intakes and micronutrient status,
      especially iron status, with approaches that improve women's status and
      reproductive health are needed to reduce LBW.

PMID- 14684393
TI  - Effects of equal weight loss with orlistat and placebo on body fat and serum
      fatty acid composition and insulin resistance in obese women.
AB  - BACKGROUND: Dietary fat has been reported to influence insulin sensitivity.
      OBJECTIVE: The objective of the study was to determine how identical weight loss
      (target: loss of 8% of body weight over 3-6 mo) in women taking orlistat or
      placebo combined with a hypocaloric diet influences body composition and insulin
      sensitivity. DESIGN: Forty-seven obese women [body mass index (in kg/m(2)): 32.1
      +/- 0.4] were randomly assigned to receive either orlistat (120 mg 3 times daily;
      n = 23) or placebo (n = 24) with a hypocaloric diet. Whole-body insulin
      sensitivity (insulin clamp technique), serum fatty acids, and body composition
      (magnetic resonance imaging) were measured before and after weight loss. RESULTS:
      The groups did not differ significantly at baseline with respect to age, body
      weight, intraabdominal and subcutaneous fat volumes, or insulin sensitivity.
      Weight loss did not differ significantly between the orlistat (7.3 +/- 0.2 kg, or
      8.3 +/- 0.1%) and placebo (7.4 +/- 0.2 kg, or 8.2 +/- 0.1%) groups. Insulin
      sensitivity improved significantly (P < 0.001) and similarly after weight loss in
      the orlistat (from 4.0 +/- 0.3 to 5.1 +/- 0.3 mg x kg fat-free mass(-1) x min(
      1)) and placebo (from 4.4 +/- 0.4 to 5.4 +/- 0.4 mg x kg fat-free mass(-1) x min(
      1)) groups. Intraabdominal fat and subcutaneous fat decreased significantly in
      both groups, but the ratio of the 2 decreased significantly only in the orlistat
      group. The proportion of dihomo-gamma-linolenic acid (20:3n-6) in serum
      phospholipids was inversely related to insulin sensitivity both before (r = 
      0.48, P < 0.001) and after (r = -0.46, P < 0.001) weight loss, but it did not
      change significantly in either group. CONCLUSIONS: Weight loss rather than
      inhibition of fat absorption enhances insulin sensitivity. A decrease in fat
      absorption by orlistat appears to favorably influence the ratio between
      intraabdominal and subcutaneous fat, which suggests that exogenous fat or its
      composition influences fat distribution.

PMID- 14684394
TI  - Body mass index and obesity-related metabolic disorders in Taiwanese and US
      whites and blacks: implications for definitions of overweight and obesity for
      Asians.
AB  - BACKGROUND: Recommendations based on scanty data have been made to lower the body
      mass index (BMI; in kg/m(2)) cutoff for obesity in Asians. OBJECTIVE: The goal
      was to compare relations between BMI and metabolic comorbidity among Asians and
      US whites and blacks. METHODS: We compared the prevalence rate, sensitivity,
      specificity, predictive values, and impact fraction of comorbidities at each BMI
      level and the BMI-comorbidity relations across ethnic groups by using data from
      the third National Health and Nutrition Examination Survey and the Nutrition and
      Health Survey in Taiwan (1993-1996). RESULTS: For most BMI values, the
      prevalences of hypertension, diabetes, and hyperuricemia were higher for
      Taiwanese than for US whites. In addition, increments of BMI corresponded to
      higher odds ratios in Taiwanese than in US whites for hypertriglyceridemia (P =
      0.01) and hypertension (P = 0.075). BMI-comorbidity relations were stronger in
      Taiwanese than in US blacks for all comorbidities studied. BMIs of 22.5, 26, and
      27.5 were the cutoffs with the highest sum of positive and negative predictive
      value for Taiwanese, US white, and US black men, respectively. The same order was
      observed for women. For BMIs >27, >85% of Taiwanese, 66% of whites, and 55% of
      blacks had at least one of the studied comorbidities. However, a cutoff close to
      the median of the studied population was often found by maximizing sensitivity
      and specificity. Reducing BMI from >25 to <25 in persons in the United States
      could eliminate 13% of the obesity comorbidity studied. The corresponding cutoff
      in Taiwan is slightly <24. CONCLUSION: These data suggest a possible need to set
      lower BMI cutoffs for Asians, but where to draw the line is a complex issue.

PMID- 14684395
TI  - Metabolic effects of caffeine in humans: lipid oxidation or futile cycling?
AB  - BACKGROUND: Caffeine ingestion stimulates both lipolysis and energy expenditure.
      OBJECTIVES: Our objectives were to determine whether the lipolytic effect of
      caffeine is associated with increased lipid oxidation or futile cycling between
      triacylglycerol and free fatty acids (FFAs) and whether the effects of caffeine
      are mediated via the sympathetic nervous system. DESIGN: Respiratory exchange and
      [1-(13)C]palmitate were used to trace lipid oxidation and FFA turnover in 8
      healthy, young men for 90 min before and 240 min after ingestion of placebo,
      caffeine (10 mg/kg), or caffeine during beta-adrenoceptor blockade. RESULTS:
      During fasting conditions, there were few differences in measured variables
      between the 3 tests. During steady state conditions (last hour of the test) after
      ingestion of caffeine, lipid turnover increased 2-fold (P < 0.005), and the mean
      (+/-SEM) thermic effect was 13.3 +/- 2.2% (P < 0.001), both of which were greater
      than after ingestion of placebo or caffeine during beta-adrenoceptor blockade.
      After ingestion of caffeine, oxidative FFA disposal increased 44% (236 +/- 21 to
      340 +/- 16 micro mol/min), whereas nonoxidative FFA disposal increased 2.3-fold
      (455 +/- 66 to 1054 +/- 242 micro mol/min; P < 0.01). In postabsorptive
      conditions, 34% of lipids were oxidized and 66% were recycled. Caffeine ingestion
      increased energy expenditure 13% and doubled the turnover of lipids, of which 24%
      were oxidized and 76% were recycled. beta-Adrenoceptor blockade decreased, but
      did not inhibit, these variables. CONCLUSIONS: Many, but not all, of the effects
      of caffeine are mediated via the sympathetic nervous system. The effect of
      caffeine on lipid mobilization in resting conditions can be interpreted in 2
      ways: lipid mobilization alone is insufficient to drive lipid oxidation, or large
      increments in lipid turnover result in small increments in lipid oxidation.

PMID- 14684396
TI  - Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular
      disease in women.
AB  - BACKGROUND: Growing evidence suggests that lycopene has significant in vitro
      antioxidant potential. Lycopene has rarely been tested in prospective studies for
      its role in cardiovascular disease (CVD) prevention. OBJECTIVE: We examined the
      association between plasma lycopene and the risk of CVD in middle-aged and
      elderly women. DESIGN: A prospective, nested, case-control study was conducted in
      39 876 women initially free of CVD and cancer in the Women's Health Study.
      Baseline blood samples were collected from 28 345 (71%) of the women. During a
      mean of 4.8 y of follow-up, we identified 483 CVD cases and 483 control subjects
      matched by age, smoking status, and follow-up time. Plasma lycopene, other
      carotenoids, retinol, and total cholesterol were measured. RESULTS: In analyses
      matched for age and smoking, with adjustment for plasma cholesterol, the relative
      risks (RRs) and 95% CIs of CVD in increasing quartiles of plasma lycopene were
      1.00 (referent), 0.78 (95% CI: 0.55, 1.11), 0.56 (0.39, 0.82), and 0.62 (0.43,
      0.90). In multivariate models, the RRs were 1.00 (referent), 0.94 (0.60, 1.49),
      0.62 (0.39, 1.00), and 0.67 (0.41, 1.11); those in the upper compared with the
      lower half of plasma lycopene had an RR of 0.66 (0.47, 0.95). For CVD, exclusive
      of angina, women in the upper 3 quartiles had a significant multivariate 50% risk
      reduction compared with those in the lowest quartile. The stepwise addition of
      individual plasma carotenoids did not affect the RRs. CONCLUSIONS: Higher plasma
      lycopene concentrations are associated with a lower risk of CVD in women. These
      findings require confirmation in other cohorts, and the determinants of plasma
      lycopene concentrations need to be better understood.

PMID- 14684397
TI  - Red wine polyphenolic compounds inhibit atherosclerosis in apolipoprotein E
      deficient mice independently of effects on lipid peroxidation.
AB  - BACKGROUND: Lipid peroxidation is thought to play an important role in the
      pathogenesis of atherosclerosis. Fatty acid peroxidation products such as
      hydroxyeicosatetraenoic acids and F(2)-isoprostanes have been found in advanced
      human atherosclerotic plaques. However, little is known about the formation of
      these products during lesion development. OBJECTIVE: This study examined stable
      biomarkers of lipid oxidative damage in relation to atherosclerotic disease
      progression in apolipoprotein E-deficient (Apoe(-/-)) mice and retardation of the
      disease by red wine polyphenols. DESIGN: One hundred male Apoe(-/-) mice and 50
      male control (C57BL/6J) mice were given a high-fat, high-cholesterol diet for 20
      wk. To examine the effect of the polyphenolic compounds on lesion development, 50
      of the Apoe(-/-) mice were also given dealcoholized red wine for the duration of
      the study. RESULTS: Aortic lipid deposition was significantly greater in the
      Apoe(-/-) mice than in the control mice (P < 0.01). Plasma and aortic F(2)
      isoprostanes did not differ between the treatment groups. Plasma concentrations
      of monocyte chemoattractant protein 1, which has been implicated in the
      development of atherosclerosis, were significantly higher in the Apoe(-/-) mice
      than in the control mice up to 16 wk (P < 0.05). Hydroxyeicosatetraenoic acid
      concentrations increased significantly over time in all groups (P < 0.05). Red
      wine polyphenols had no effect on markers of lipid peroxidation or monocyte
      chemoattractant protein 1 concentrations, but lipid deposition in the aorta at
      age 26 wk was significantly less in the mice given red wine than in those not
      given red wine. CONCLUSION: These results suggest that lipid deposition is
      independent of lipid oxidation and that the protective action of red wine
      polyphenols is independent of any antioxidant action of these compounds.

PMID- 14684398
TI  - A decrease in physical activity affects appetite, energy, and nutrient balance in
      lean men feeding ad libitum.
AB  - BACKGROUND: It is not clear how decreased activity quantitatively affects energy
      balance (EB) in subjects feeding ad libitum. OBJECTIVE: We assessed the effect of
      an imposed sedentary routine on appetite, energy intake (EI), EB, and nutrient
      balance in lean men for 7 d. DESIGN: Six men with a mean (+/-SD) age of 23.0 +/-
      2.3 y, weight of 69.2 +/- 11.4 kg, and height of 1.76 +/- 0.07 m were each
      studied twice during a sedentary [1.4 x resting metabolic rate (RMR)] and a
      moderately active (1.8 x RMR) regimen. During each treatment, they resided in the
      whole-body indirect calorimeter for the 7 d and had ad libitum access to a medium
      fat diet of constant, measurable composition. Meal size, frequency, and
      composition were continually monitored. Motivation to eat was recorded during
      waking hours. Subjects were weighed in light clothing each morning, and their
      weight was corrected to nude. RESULTS: Energy expenditure was 9.7 and 12.8 MJ/d
      [P < 0.01; SE of the difference between means (SED) = 0.41] during the sedentary
      and active regimens, respectively. EI was 13.5 and 14.4 MJ/d (P = 0.463, SED =
      1.06), respectively. There was no regimen effect on hunger, appetite, or body
      weight. By day 7, cumulative EB was 26.3 and 11.1 MJ, respectively. CONCLUSIONS:
      Reducing a level of physical activity from 1.8 to 1.4 x RMR can markedly affect
      EB. A sedentary routine does not induce a compensatory reduction of EI and leads
      to a significantly positive EB, most of which is stored as fat.

PMID- 14684399
TI  - Dietary iron intake and blood donations in relation to risk of type 2 diabetes in
      men: a prospective cohort study.
AB  - BACKGROUND: Excessive iron stores may promote insulin resistance and lead to the
      development of type 2 diabetes. However, prospective data relating iron intake
      and blood donations (determinants of body iron stores) to diabetes incidence are
      limited. OBJECTIVE: We examined iron intake and blood donations in relation to
      the incidence of type 2 diabetes. DESIGN: We followed men aged 40-75 y who
      participated in the Health Professionals' Follow-up Study; were free of diabetes,
      cardiovascular disease, and cancer in 1986; and provided dietary data (n = 38
      394). Of those participants, 33 541 also provided a history of blood donation
      during the past 30 y in 1992. RESULTS: During 12 y of follow-up, we ascertained
      1168 new cases of type 2 diabetes. After adjustment for age, body mass index, and
      other diabetes risk factors, total iron intake was not associated with the risk
      of type 2 diabetes. Intakes of total heme iron [multivariate relative risk (RR)
      for extreme quintiles: 1.28; 95% CI: 1.02, 1.61; P for trend = 0.045] and of heme
      iron from red meat (RR: 1.63; 1.26, 2.10; P for trend < 0.001) were associated
      with an increased risk. However, heme-iron intake from sources other than red
      meat was not associated with diabetes risk (RR: 0.99; 0.81, 1.22). No significant
      associations were found between blood donation and the risk of type 2 diabetes.
      CONCLUSIONS: Heme-iron intake from red meat sources is positively associated with
      the risk of type 2 diabetes. Total iron intake, heme-iron intake from non-red
      meat sources, and blood donations are not related to the risk of type 2 diabetes.

PMID- 14684400
TI  - Variation in plasma cystathionine and its relation to changes in plasma
      concentrations of homocysteine and methionine in healthy subjects during a 24-h
      observation period.
AB  - BACKGROUND: Plasma cystathionine measurement may be a useful complement to total
      homocysteine measurement in the assessment of B vitamin status. Information on
      the within-person variation in cystathionine is currently sparse. OBJECTIVE: The
      goal was to study the daily variation in plasma cystathionine concentrations in
      healthy subjects. DESIGN: Twelve subjects (aged 22-29 y) were followed for 24 h.
      During the observation period, the subjects received a breakfast (containing 15
      18 g protein) at 0900 and a beef dinner (containing approximately 50 g protein)
      at 1500. Multiple blood samples for metabolite analyses were collected during the
      day, and a final sample was obtained the next morning. The results are expressed
      as medians and interquartile ranges. RESULTS: All subjects had normal fasting
      cystathionine concentrations [0.120 (0.100-0.160) micro mol/L]. Cystathionine
      concentrations increased significantly after breakfast, reached a maximum after 4
      h of 142.4% (100.0-170.3%) of the fasting concentration, and then declined to
      fasting concentrations before dinner. After dinner, plasma cystathionine started
      to increase within 0.5 h and reached a maximum after 6 h [281.3% (194.1-351.4%)
      of the concentration measured before dinner]. The changes in plasma methionine
      and total homocysteine concentrations during the day were less pronounced.
      CONCLUSION: Food intake, even of foods with low protein content, causes an
      increase in plasma cystathionine concentrations that is more pronounced than the
      concomitant changes in total homocysteine and methionine. In studies including
      plasma cystathionine measurement, blood sampling in the fasting state should be
      considered.

PMID- 14684401
TI  - Prospective study of serum selenium concentrations and esophageal and gastric
      cardia cancer, heart disease, stroke, and total death.
AB  - BACKGROUND: We previously reported an inverse association between prediagnostic
      serum selenium concentrations and the risk of esophageal squamous cell carcinoma
      (ESCC) and gastric cardia cancer (GCC) but not gastric noncardia cancer (GNCC) in
      a nested study from the Nutrition Intervention Trial in Linxian, China.
      OBJECTIVE: We examined the relation between baseline serum selenium and the
      subsequent risk of death from ESCC, GCC, GNCC, heart disease (HD), stroke, and
      total death over 15 y of follow-up (1986-2001). DESIGN: We measured baseline
      serum selenium concentrations in 1103 subjects randomly selected from a larger
      trial cohort. We identified 516 deaths during the 15-y follow up, including 75
      from ESCC, 36 from GCC, 116 from HD, and 167 from stroke. Relative risks (RRs)
      and 95% CIs were estimated by using Cox proportional hazards regression models.
      Reported RRs estimated the change in risk conferred by a 25% increase in serum
      selenium relative to the population distribution. All estimates were adjusted for
      sex, age, smoking, drinking, and serum cholesterol. RESULTS: We found significant
      inverse associations between baseline serum selenium and death from ESCC (RR:
      0.83; 95% CI: 0.71, 0.98) and GCC (0.75; 0.59, 0.95). Trends toward inverse
      associations were noted for death from HD (0.89; 0.78, 1.01; P = 0.07), but no
      association was noted for total death (0.96; 0.90, 1.02) or stroke (0.99; 0.88,
      1.11). CONCLUSION: Population-wide selenium supplementation in the region of
      China with low serum selenium and high incidences of ESCC and GCC merits serious
      consideration.

PMID- 14684402
TI  - Vitamin E bioavailability from fortified breakfast cereal is greater than that
      from encapsulated supplements.
AB  - BACKGROUND: Conflicting results from vitamin E intervention studies suggest
      supplemental vitamin E malabsorption. OBJECTIVE: We compared vitamin E
      bioavailability from a supplement with that from a fortified breakfast cereal.
      DESIGN: Vitamin E bioavailability was evaluated by using deuterium-labeled all
      rac-alpha-tocopherol in three 4-d trials (2 wk apart). Five fasting subjects
      sequentially consumed the following (with 236 mL fat-free milk): 400 IU d(9)
      alpha-tocopheryl acetate (400-IU capsule), 41 g ready-to-eat wheat cereal
      containing 30 IU d(9)-alpha-tocopheryl acetate (30-IU cereal), and 45 g cereal
      containing 400 IU d(9)-alpha-tocopheryl acetate (400-IU cereal). Five months
      later (trial 4), they consumed a 400-IU capsule with 41 g vitamin E-free cereal.
      Blood was obtained up to 72 h after the start of each trial. RESULTS: The mean
      (+/-SD) vitamin E bioavailabilities of the 30-IU cereal and the 400-IU cereal
      were 6 +/- 2 and 26 +/- 8 times, respectively, the vitamin E bioavailability of
      the 400-IU capsule. The areas under the 0-72-h d(9)-alpha-tocopherol curves for
      the 400-IU capsule, the 30-IU cereal, and the 400-IU cereal were 30 +/- 7, 153 +/
      43, and 765 +/- 164 micro mol. h/L (all trial comparisons, P < 0.0001). In trial
      4, 3 subjects barely responded and 2 subjects had areas under the curve that were
      similar to their 400-IU cereal responses. CONCLUSION: The low bioavailability of
      vitamin E from the 400-IU capsule and the variability observed when the capsule
      was consumed with cereal suggest that encapsulated vitamin E is poorly absorbed
      when consumed with a low-fat meal and that bioavailability can be enhanced by
      food fortification with vitamin E.

PMID- 14684403
TI  - Development of a rapid enzyme immunoassay for the detection of retinol-binding
      protein.
AB  - BACKGROUND: Retinol-binding protein (RBP) was chosen as a surrogate marker for
      retinol because of the close correspondence between retinol and RBP. OBJECTIVE:
      To meet the need for rapid, cost-effective determination of vitamin A status in
      populations, a quantitative enzyme immunoassay (EIA) for detection of RBP was
      developed. DESIGN: The resulting RBP EIA, a competitive assay, uses RBP adsorbed
      to microtest strip wells to compete with RBP in serum. The assay takes
      approximately 40 min. RESULTS: With a reference panel of sera, test accuracy was
      found to be within 4% of expected values through the calibrated range of 0.48
      1.92 micro mol RBP/L (10-40 micro g RBP/mL). Intraassay and interassay
      variability averaged 6.7% and 8.9%, respectively. Specificity testing showed no
      interference from other serum proteins, prealbumin, rheumatoid factor, bilirubin,
      estrogen, or C-reactive protein. The RBP EIA provided linear results between 0.43
      and 1.80 micro mol RBP/L (9 and 38 micro g RBP/mL). Preliminary laboratory
      evaluations indicated that the RBP EIA correlates well with radial
      immunodiffusion for RBP and with HPLC for retinol, the current reference
      standard. A field evaluation in a population at risk for vitamin A deficiency
      (VAD) resulted in close correlation between RBP EIA measures and retinol measures
      by HPLC (R(2) = 0.82). CONCLUSIONS: The RBP EIA is as reliable in estimating VAD
      as is HPLC retinol. After successful validations, the test should enable public
      health authorities to rapidly monitor VAD and track vitamin A status in
      populations.

PMID- 14684404
TI  - Erythorbic acid is a potent enhancer of nonheme-iron absorption.
AB  - BACKGROUND: Erythorbic acid, a stereoisomer of ascorbic acid with similar
      physicochemical properties, is widely used as an antioxidant in processed foods.
      OBJECTIVES: The aims of the present study were to evaluate the effect of
      erythorbic acid on iron absorption from ferrous sulfate at molar ratios of 2:1
      and 4:1 (relative to iron) and to compare the effect of erythorbic acid directly
      with that of ascorbic acid at a molar ratio of 4:1. DESIGN: Iron absorption from
      iron-fortified cereal was measured in 10 women on the basis of erythrocyte
      incorporation of stable iron isotopes ((57)Fe or (58)Fe) 14 d after
      administration. Each woman consumed 4 ferrous-sulfate-fortified test meals
      (containing 5 mg Fe/meal) with or without added erythorbic or ascorbic acid. The
      data were evaluated by use of paired t tests, and the results are presented as
      geometric means. RESULTS: Iron absorption from the test meal without any added
      enhancer was 4.1%. The addition of erythorbic acid (at molar ratios of 2:1 and
      4:1 relative to iron) increased iron absorption 2.6-fold (10.8%; P < 0.0001) and
      4.6-fold (18.8%; P < 0.0001), respectively. The addition of ascorbic acid (molar
      ratio of 4:1) increased iron absorption 2.9-fold (11.7%; P = 0.0004). At a molar
      ratio of 4:1, erythorbic acid was 1.6-fold (P = 0.0002) as potent an enhancer of
      iron absorption as was ascorbic acid. CONCLUSION: Although erythorbic acid is a
      potent enhancer of iron absorption, its lack of antiscorbutic activity limits its
      usefulness in iron-fortification programs. However, it may play a major role in
      enhancing iron bioavailability from mixed diets that include foods preserved with
      erythorbic acid.

PMID- 14684405
TI  - Maternal circulating nutrient concentrations in pregnancy: implications for birth
      and placental weights of term infants.
AB  - BACKGROUND: Compromised fetal growth may program chronic diseases of adulthood,
      and it has been suggested that maternal nutrition is a major determinant of fetal
      growth. We previously found no clinically significant associations between
      maternal diet and the size of the infant and placenta at birth in a large cohort
      of white women living in the United Kingdom. OBJECTIVE: The objective was to
      examine the relations between indexes of maternal nutritional status in pregnancy
      and the birth and placental weights of infants born at term. DESIGN: We conducted
      a prospective cohort study of 798 white nulliparous women with singleton
      pregnancies. Blood samples were obtained at approximately 16 and 28 wk of
      gestation. RESULTS: The concentration of most nutrients was not associated with
      pregnancy outcome. High retinol and hemoglobin concentrations in late, but not in
      early, pregnancy were strongly and independently associated with lower birth
      weight and smaller placental size at birth. Each 0.1- micro mol increase in
      retinol predicted a 20.8-g (95% CI: 9.2, 32.5 g) decrease in birth weight (P <
      0.001), and each 0.1-g/L increase in hemoglobin predicted a 61.5-g (95% CI: 28.5,
      94.4 g) decrease in birth weight (P < 0.001). CONCLUSIONS: We found negative
      associations between birth and placental weights and maternal retinol and
      hemoglobin concentrations. These relations may be causal or may reflect an
      underlying metabolic dysfunction, such as failure of plasma volume expansion. Our
      results provide no evidence that having high circulating nutrient concentrations,
      for example, through the use of supplements, would improve infant and placental
      growth.

PMID- 14684406
TI  - Iron, zinc, and copper concentrations in breast milk are independent of maternal
      mineral status.
AB  - BACKGROUND: Little is known about the regulation of iron, zinc, and copper in
      breast milk and the transport of these minerals across the mammary gland
      epithelium. OBJECTIVE: The objective was to study associations between breast
      milk concentrations of iron, zinc, and copper and maternal mineral status.
      DESIGN: Milk samples from 191 Swedish and Honduran mothers were collected at 9 mo
      postpartum. Iron, zinc, and copper concentrations were measured by atomic
      absorption spectrometry. Blood samples from mothers were analyzed for plasma zinc
      and copper and 4 indexes of iron status: hemoglobin, plasma ferritin, soluble
      transferrin receptors, and zinc protoporphyrin. Complementary food energy (CFE)
      intake was used as an inverse proxy for breast-milk intake. RESULTS: Mean (+/-SD)
      breast-milk concentrations of iron were lower in the Honduran than in the Swedish
      mothers (0.21 +/- 0.25 compared with 0.29 +/- 0.21 mg/L; P < 0.001), and mean
      breast-milk concentrations of zinc and copper were higher in the Honduran than in
      the Swedish mothers [0.70 +/- 0.18 compared with 0.46 +/- 0.26 mg/L (P < 0.001)
      and 0.16 +/- 0.21 compared with 0.12 +/- 0.22 mg/L (P = 0.001), respectively].
      Milk iron was positively correlated with CFE intake (r = 0.24, P = 0.001) but was
      not significantly correlated with any iron-status variable. Milk zinc was
      negatively correlated with CFE intake (r = -0.24, P = 0.001) but was not
      significantly correlated with maternal plasma zinc. Milk copper was not
      significantly correlated with CFE intake or maternal plasma copper. CONCLUSIONS:
      Milk iron, zinc, and copper concentrations at 9 mo postpartum are not associated
      with maternal mineral status, which suggests active transport mechanisms in the
      mammary gland for all 3 minerals. Milk iron concentrations increase and milk zinc
      concentrations decrease during weaning [corrected]

PMID- 14684407
TI  - A prospective, partially randomized study of pregnancy outcomes and hematologic
      responses to oral and intramuscular iron treatment in moderately anemic pregnant
      women.
AB  - BACKGROUND: Daily oral iron supplementation during pregnancy fails to reduce the
      prevalence of anemia. However, 2 or 3 intramuscular doses of iron given at
      monthly intervals were recently found to be effective. OBJECTIVE: We compared the
      safety and efficacy in treating pregnancy anemia of 3 intramuscular doses of iron
      given at monthly intervals with those of daily oral iron supplementation. DESIGN:
      In a prospective, partially randomized study, 148 pregnant women received daily
      oral doses of 100 mg elemental Fe and 500 micro g folic acid, and 106 pregnant
      women received 3 intramuscular doses of 250 mg elemental Fe as iron dextran at 1
      mo intervals and oral doses of 5 mg folic acid twice weekly. One hundred women in
      each group completed the study. Changes in hemoglobin, iron indicators, pregnancy
      outcomes, and birth weight were compared between the 2 groups. RESULTS:
      Hemoglobin and iron indicators improved significantly with both treatments. The
      increase in serum ferritin concentration after parenteral iron treatment was
      significantly higher than that after oral iron treatment. No significant
      differences between the 2 groups in pregnancy outcomes and birth weight were
      observed. Systemic side effects were more common in the parenteral iron group,
      whereas gastrointestinal side effects were more common in the oral iron group.
      CONCLUSIONS: The intramuscular administration of 3 doses of 250 mg Fe at monthly
      intervals appears to have good compliance and efficacy and may be used in women
      who cannot tolerate oral administration of iron. However, intramuscular
      administration of iron is appropriate only in hospital settings well equipped to
      treat anaphylactic crises.

PMID- 14684408
TI  - Dealcoholized red wine decreases atherosclerosis in apolipoprotein E gene
      deficient mice independently of inhibition of lipid peroxidation in the artery
      wall.
AB  - BACKGROUND: Oxidation of LDL is thought to be important in the development of
      atherosclerosis. Effective protection against lipoprotein oxidation is achieved
      by the use of alpha-tocopherol plus coantioxidants, ie. compounds that prevent
      the prooxidant activity of the vitamin. Wines contain a large number of
      polyphenols, micronutrients that may act as coantioxidants and may enhance the in
      vivo antioxidant activity of vitamin E. OBJECTIVE: We examined whether wines and
      wine-derived fractions are able to act synergistically with vitamin E in vitro
      and whether dealcoholized red wine (DRW) retards the development of
      atherosclerosis. DESIGN: Synergy with vitamin E was assessed in vitro by the
      ability of red and white wines to both attenuate alpha-tocopheroxyl radicals and
      inhibit in vitro oxidation of LDL in the presence of vitamin E. Female, 6-8-wk
      old apolipoprotein E gene-deficient mice were fed a normal nonpurified stock diet
      for 24 wk to assess the effect on atherosclerosis of DRW at a dose equivalent to
      200 mL x 80 kg body wt(-1) x d(-1). RESULTS: DRW synergized with vitamin E as
      effectively as did red and white wine, and phenolic acids accounted for most of
      this activity. Administration of DRW increased plasma and aortic antioxidants
      concentrations and the resistance of plasma lipoproteins to ex vivo oxidation.
      Whereas lipoprotein oxidation in the artery wall was not affected, DRW
      significantly decreased atherosclerosis in the aortic arch, but not in the root,
      as assessed by morphometry. CONCLUSIONS: DRW contains polyphenolic compounds
      capable of synergizing with vitamin E, and long-term moderate consumption of DRW
      can decrease atherosclerosis in apolipoprotein E gene-deficient mice.

PMID- 14684409
TI  - Lower estimates of net endogenous non-carbonic acid production are positively
      associated with indexes of bone health in premenopausal and perimenopausal women.
AB  - BACKGROUND: The link between acid-base homeostasis and skeletal integrity has
      gained increasing prominence in the literature. Estimation of the net rate of
      endogenous non-carbonic acid production (NEAP) from dietary protein and potassium
      content enables exploration of the effects of dietary acidity or alkalinity on
      bone. OBJECTIVE: The study aimed to ascertain whether lower dietary acidity
      (lower dietary protein intake but higher potassium intake-ie, low estimate of
      NEAP) was associated with greater axial and peripheral bone mass and less bone
      turnover, independent of key confounding factors. DESIGN: Baseline (cross
      sectional) results of a population-based study were examined further. The
      database includes spine and hip bone mineral density (BMD) in 1056 premenopausal
      or perimenopausal women aged 45-54 y and forearm bone mass and the urinary
      markers of bone resorption in 62 women. A validated food-frequency questionnaire
      was used to measure dietary intakes. RESULTS: Lower estimates of energy-adjusted
      NEAP were correlated with greater spine and hip BMD and greater forearm bone mass
      (P < 0.02 to P < 0.05). Hip and forearm bone mass decreased significantly across
      increasing quartiles of energy-adjusted NEAP (P < 0.02 to P < 0.03), and trends
      at the spine were similar (P < 0.09). Differences remained significant after
      adjustment for age, weight, height, and menstrual status. Lower estimates of
      energy-adjusted NEAP were also correlated with lower excretion of
      deoxypyridinoline and were significant predictors of spine and forearm bone mass.
      CONCLUSIONS: These novel findings provide evidence of a positive link between a
      ratio of lower protein to higher potassium dietary intake (ie, less dietary acid)
      and skeletal integrity.

PMID- 14684410
TI  - Dose response of bone mass to dietary arachidonic acid in piglets fed cow milk
      based formula.
AB  - BACKGROUND: The addition of arachidonic acid (AA) and docosahexaenoic acid (DHA)
      to infant formula was recently approved in North America. In piglets, dietary AA
      is linked to elevations in bone mass. OBJECTIVE: The objective was to investigate
      the effects of varied amounts of dietary AA on bone modeling and bone mass with
      the use of the piglet model for infant nutrition. DESIGN: Male piglets (n = 32)
      were randomly assigned to receive 1 of 4 formulas supplemented with AA (0.30%,
      0.45%, 0.60%, or 0.75% of fat) plus DHA (0.1% of fat) from days 5 to 20 of life.
      Measurements included biomarkers of bone modeling, fatty acid status, and whole
      body and femur bone mineral content; bone area was measured by dual-energy X-ray
      absorptiometry. Differences among groups were detected with two-factor analysis
      of variance. Regression analyses were used to determine factors responsible for
      bone mineral content after dietary AA was accounted for. RESULTS: Proportions of
      AA in plasma, liver, and adipose were modified by the dietary treatments, but
      bone modeling was not affected. Liver AA was positively related to plasma insulin
      like growth factor 1 and calcitriol and urinary N-telopeptide. Whole-body bone
      mineral content was elevated in the piglets fed 0.60% and 0.75% AA and was best
      predicted by dietary AA and bone resorption. CONCLUSIONS: This study confirms
      that dietary AA alters bone mass and clarifies the best amount of AA to add to
      the diet of pigs born at term. Because the amount of dietary DHA was held
      constant, whether other amounts of DHA are related to bone mass requires
      investigation.

PMID- 14684411
TI  - Longitudinal changes in bone metabolism and bone mineral content in children with
      celiac disease during consumption of a gluten-free diet.
AB  - BACKGROUND: A gluten-free diet (GFD) rapidly corrects the bone mineral deficit of
      children with untreated celiac disease. The mechanisms underlying such changes
      are still poorly understood. OBJECTIVE: In a longitudinal study, we monitored
      changes in bone metabolism during consumption of a GFD. DESIGN: We studied 22
      white patients with celiac disease (11 girls) aged 10.5 +/- 1.0 y at the time of
      diagnosis. We compared bone metabolism and bone mass values in these patients
      with those in 428 healthy white children aged 11.3 +/- 0.2 y. Bone-specific
      alkaline phosphatase (a bone formation index) and N-terminal telopeptide of type
      I collagen (NTx; a bone resorption marker) were measured at the time of diagnosis
      and after 2, 6, and 12 mo of the GFD. Bone mineral content was measured at the
      lumbar spine and for the whole skeleton. RESULTS: The bone mineral content of
      patients was significantly lower than that of control subjects at the time of
      diagnosis but not after 1 y of the GFD. Serum bone-specific alkaline phosphatase
      concentrations of patients were significantly lower than those of control
      subjects at the time of diagnosis (P = 0.0064) and increased gradually and
      significantly during the GFD (ANOVA F = 4.71; P = 0.024). Conversely, patients
      with untreated disease had significantly higher urinary concentrations of NTx
      than did healthy control subjects (P < 0.0001). Urinary concentrations of NTx
      were not significantly affected by treatment (P = 0.37). CONCLUSIONS: The rate of
      bone metabolism is altered in children with untreated celiac disease, and these
      alterations may be the cause of osteopathy. Remarkable changes occur after the
      initiation of a GFD, and they result in a more balanced equilibrium.

PMID- 14684412
TI  - Nutritional associations with bone loss during the menopausal transition:
      evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable
      nutrients and of a detrimental effect of fatty acids.
AB  - BACKGROUND: The menopausal transition is characterized by rapid bone loss. Few
      data exist on the role of nutrition. OBJECTIVE: The objective of the study was to
      ascertain which dietary factors influence perimenopausal skeletal loss. DESIGN: A
      longitudinal study was conducted of 891 women aged 45-55 y at baseline and 50-59
      y at follow-up 5-7 y later. Bone mineral density (BMD) was measured by using dual
      energy X-ray absorptiometry at the lumbar spine and femoral neck (FN). Nutrient
      intakes were assessed after the baseline visit and 5 y later, by using the same
      food-frequency questionnaire. RESULTS: After adjustment for energy intake and
      other confounders, higher intakes of calcium were correlated with change in FN
      BMD (ie, reduced loss) (r = 0.073, P < 0.05), and the intake of modest amounts of
      alcohol was associated with less lumbar spine bone loss (P < 0.01 for quartile of
      alcohol intake). Greater FN BMD loss was associated with increased intake of
      polyunsaturated fatty acids (r = -0.110, P < 0.01), monounsaturated fatty acids
      (r = -0.069, P < 0.05), retinol (r = -0.067; P < 0.05), and vitamin E (r = 
      0.110; P < 0.01). The latter 2 nutrients were highly correlated with
      polyunsaturated fatty acids. For premenopausal women, calcium and nutrients found
      in fruit and vegetables (vitamin C, magnesium, and potassium) were associated
      with FN BMD, and calcium, vitamin C, and magnesium were associated with change in
      FN BMD. CONCLUSIONS: Although menopausal status and hormone replacement therapy
      use dominate women's bone health, diet may influence early postmenopausal bone
      loss. Fruit and vegetable intake may protect against premenopausal bone loss.

PMID- 14684413
TI  - n-3 Fatty acids and cardiovascular disease.

PMID- 14684414
TI  - Mature dendritic cells can enhance CD8+ cell noncytotoxic anti-HIV responses: the
      role of IL-15.
AB  - The CD8+ cell noncytotoxic anti-HIV response (CNAR) is associated with a long
      term healthy clinical state in HIV-infected individuals. Over time CNAR is
      reduced concomitant with progression to disease. In studies to evaluate whether
      the interaction between CD8+ cells and dendritic cells (DCs) could increase CNAR,
      CD8+ cells from individuals who showed a decrease in this antiviral activity were
      cocultured with monocyte-derived dendritic cells matured with CD40 ligand. After
      coculture with these mature DCs, the CD8+ cells showed an increase in CNAR
      greater than that observed with CD8+ cells costimulated with CD3/CD28 antibodies.
      This antiviral response appeared to be mediated primarily by production of
      interleukin-15 (IL-15) by the mature DCs. Purified IL-15 also enhanced CNAR,
      whereas IL-12 showed no substantial effect. These studies provide another
      potential approach by which the immune system in HIV infection could be restored
      by cytokine therapy, particularly IL-15 administration.

PMID- 14684415
TI  - Magnetic resonance angiography in children with sickle cell disease and abnormal
      transcranial Doppler ultrasonography findings enrolled in the STOP study.
AB  - The stroke prevention study in sickle cell disease (STOP) demonstrated a 90%
      reduction in stroke risk with transfusion among patients with time-averaged mean
      cerebral blood velocity (TAMV) of 200 cm/s or more as measured by transcranial
      Doppler (TCD). In STOP, 232 brain magnetic resonance angiograms (MRAs) were
      performed on 100 patients, 47 in the transfusion arm and 53 in the standard care
      arm. Baseline MRA findings were interpreted as normal in 75 patients and as
      indicating mild stenosis in 4 patients and severe stenosis in 21 patients. Among
      35 patients who underwent magnetic resonance angiography within 30 days of random
      assignment, the TAMV was significantly higher in 7 patients with severe stenosis
      compared with 28 patients with normal MRA findings or mild stenosis (276.7 +/- 34
      vs 215 +/- 15.6 cm/s; P<.001). In the standard care arm, 4 of 13 patients with
      abnormal MRA findings had strokes compared with 5 of 40 patients with normal MRA
      findings (P=.03). In this arm, TAMV became normal (less than 170 cm/s) or
      conditional (170-199 cm/s) in 26 of 38 patients with normal or mildly abnormal
      baseline MRA but remained abnormal in 8 of 10 patients with severely abnormal
      baseline MRA. These results suggest that TCD often detects flow abnormalities
      indicative of stroke risk before MRA lesions become evident. Furthermore,
      patients with abnormal MRA findings and higher TCD velocities are at higher risk
      for stroke, and their cerebral TAMVs are unlikely to decrease without
      transfusion.

PMID- 14684416
TI  - The WHO classification of MDS does make a difference.
AB  - The purpose of this study was to determine the facility and reliability of the
      World Health Organization (WHO) classification of myelodysplastic syndromes
      (MDSs) with several observers reviewing the same diagnostic specimens. We also
      wanted to determine if the WHO classification provided additional information
      about predictability of clinical response outcome. To accomplish these goals we
      reviewed 103 previously diagnosed cases of low-risk MDS. We found 92%
      interobserver agreement (P <.001). Sixty-four of these patients had been entered
      into clinical trials using growth factors by the Nordic MDS Study Group. The WHO
      classification reliably predicted therapeutic response to the combination of
      granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Epo). The
      response rate differed significantly between refractory anemia with ringed
      sideroblasts (RARS) and refractory anemia with multilineage dysplasia and ringed
      sideroblasts (RCMD/RS) with regard to therapeutic response (75% versus 9%; P
      =.003). Also, in the group of patients with less than 5% marrow blasts, there was
      a difference in median survival between patients with unilineage dysplasia (51%
      surviving at 67 months) and those with multilineage dysplasia (median survival,
      28.5 months; P =.03).

PMID- 14684419
TI  - The epidemiology of chronic hepatitis C infection in survivors of childhood
      cancer: an update of the St Jude Children's Research Hospital hepatitis C
      seropositive cohort.
AB  - Childhood cancer survivors transfused before 1992 are at risk for chronic
      hepatitis C (HCV) infection. In 1995, St Jude Children's Research Hospital
      initiated an epidemiologic study of childhood cancer survivors with transfusion
      acquired HCV. Of the 148 survivors with HCV confirmed by second-generation enzyme
      immunoassay, 122 consented to participate in the study. Their current median age
      is 29 years (range, 9 to 47 years). At enrollment, polymerase chain reaction
      (PCR) testing indicated chronic infection in 81.1%; genotype 1 was the most
      common viral genotype. Liver biopsy in 60 patients at a median of 12.4 years from
      the diagnosis of malignancy showed mild (28.8%) or moderate (35.6%) fibrosis;
      13.6% had cirrhosis. Elevated body mass index was associated with histologic
      findings of increased steatosis (P=.008). Antimetabolite chemotherapy exposure
      was associated with early progression of fibrosis. Significant quality-of-life
      deficits were observed in noncirrhotic adult survivors. Antiviral therapy
      resulted in clearance of infection in 17 (44%) of 38 patients to date. Six
      patients have died; 1 patient with decompensated cirrhosis died of variceal
      bleeding. Despite a young age at HCV infection, the progression of liver disease
      in childhood cancer survivors is comparable to that seen in adults.

PMID- 14684420
TI  - CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed
      cryoglobulinemia vasculitis.
AB  - Patients who are chronically infected with hepatitis C virus (HCV) often develop
      mixed cryoglobulinemia (MC), a B-cell proliferative disorder with polyclonal
      activation and autoantibody production. We investigated if MC is associated with
      a deficit of CD4(+)CD25(+) immunoregulatory T (Treg) cells, which have been shown
      to control autoimmunity. Because Treg cells express higher amounts of CD25 than
      activated CD4(+) T cells, we analyzed blood CD4(+)CD25(high) Treg cells in 69
      untreated patients chronically infected with HCV. Treg cell frequency in patients
      without MC (8.8% +/- 2.3%) or with asymptomatic MC (7.4% +/- 2.1%) was comparable
      to that of healthy controls (7.9% +/- 1.3%). In contrast, it was significantly
      reduced in symptomatic MC patients (2.6% +/- 1.2%, P <.001) even when compared to
      a panel of untreated HCV(-) patients with different inflammatory disorders (6.2%
      +/- 0.8%, P <.0001). In symptomatic MC patients, the purified remaining
      CD4(+)CD25(+) T cells retained suppressive activity in vitro. These results,
      together with experimental data showing that depletion of Treg cells induces
      autoimmunity, suggest a major role of Treg cell deficiency in HCV-MC vasculitis
      and this is the first report of a quantitative Treg cell deficiency in virus
      associated autoimmunity.

PMID- 14684422
TI  - Gene expression profile of adult T-cell acute lymphocytic leukemia identifies
      distinct subsets of patients with different response to therapy and survival.
AB  - Gene expression profiles were examined in 33 adult patients with T-cell acute
      lymphocytic leukemia (T-ALL). Nonspecific filtering criteria identified 313 genes
      differentially expressed in the leukemic cells. Hierarchical clustering of
      samples identified 2 groups that reflected the degree of T-cell differentiation
      but was not associated with clinical outcome. Comparison between refractory
      patients and those who responded to induction chemotherapy identified a single
      gene, interleukin 8 (IL-8), that was highly expressed in refractory T-ALL cells
      and a set of 30 genes that was highly expressed in leukemic cells from patients
      who achieved complete remission. We next identified 19 genes that were
      differentially expressed in T-ALL cells from patients who either had a relapse or
      remained in continuous complete remission. A model based on the expression of 3
      of these genes was predictive of duration of remission. The 3-gene model was
      validated on a further set of T-ALL samples from 18 additional patients treated
      on the same clinical protocol. This study demonstrates that gene expression
      profiling can identify a limited number of genes that are predictive of response
      to induction therapy and remission duration in adult patients with T-ALL.

PMID- 14684423
TI  - GPIb-dependent platelet activation is dependent on Src kinases but not MAP kinase
      or cGMP-dependent kinase.
AB  - Glycoprotein Ib-IX-V (GPIb-IX-V) mediates platelet tethering to von Willebrand
      factor (VWF), recruiting platelets into the thrombus, and activates integrin
      alphaIIbbeta3 through a pathway that is dependent on Src kinases. In addition,
      recent reports indicate that activation of alphaIIbbeta3 by VWF is dependent on
      protein kinase G (PKG) and mitogen-activated protein (MAP) kinases. The present
      study compares the importance of these signaling pathways in the activation of
      alphaIIbbeta3 by GPIb-IX-V. In contrast to a recent report, VWF did not promote
      an increase in cyclic guanosine monophosphate (cGMP), while agents that elevate
      cGMP, such as the nitrous oxide (NO) donor glyco-SNAP-1 (N-(beta-D
      glucopyranosyl)-N2-acetyl-S-nitroso-D,L-penicillaminamide) or the type 5
      phosphosdiesterase inhibitor, sildenafil, inhibited rather than promoted
      activation of alphaIIbbeta3 by GPIb-IX-V and blocked aggregate formation on
      collagen at an intermediate rate of shear (800 s(-1)). Additionally, sildenafil
      increased blood flow in a rabbit model of thrombus formation in vivo. A novel
      inhibitor of the MAP kinase pathway, which is active in plasma, PD184161, had no
      effect on aggregate formation on collagen under flow conditions, whereas a novel
      inhibitor of Src kinases, which is also active in plasma, PD173952, blocked this
      response. These results demonstrate a critical role for Src kinases but not MAP
      kinases in VWF-dependent platelet activation and demonstrate an inhibitory role
      for cGMP-elevating agents in regulating this process.

PMID- 14684425
TI  - Involvement of apoptosis signal-regulating kinase-1 on angiotensin II-induced
      monocyte chemoattractant protein-1 expression.
AB  - OBJECTIVE: Monocyte chemoattractant protein 1 (MCP-1) could contribute to
      enhanced leukocyte recruitment and activation resulting in chronic tissue damage.
      However, little is known about the molecular mechanisms of cardiac MCP-1
      expression. To elucidate these molecular mechanisms, angiotensin II-induced
      expression of MCP-1 was examined in cultured rat neonatal ventricular
      cardiomyocytes and fibroblasts by adenovirus gene transfer. METHODS AND RESULTS:
      MCP-1 mRNA increased 3.6-fold in cardiac fibroblasts at 3 hours after 100 nmol/L
      angiotensin-II stimulation (P<0.01), whereas MCP-1 mRNA in cardiomyocytes was
      unchanged. Angiotensin II significantly enhanced JNK, p38MAPK, and nuclear factor
      kappaB (NF-kappaB) activities of cardiac fibroblasts. Wild-type ASK-1 increased
      MCP-1 expression of cardiac fibroblasts, whereas dominant negative mutant of ASK
      1 (DN-ASK), dominant negative mutant of p38MAPK (DN-p38MAPK), and pyrrolidine
      dithiocarbamate significantly inhibited such expression. The increased MCP-1 mRNA
      expression in wild-type ASK-1 transfected fibroblasts was inhibited by
      cotransfection with adenovirus expressing DN-p38MAPK. On the contrary, the
      decreased MCP-1 mRNA expression in DN-ASK transfected cells was increased by
      cotransfection with adenovirus expressing constitutively active MKK6.
      CONCLUSIONS: Angiotensin II induced MCP-1 gene expression in cardiac fibroblasts.
      The angiotensin II-induced activation of ASK-1 followed by p38MAPK and NF-kappaB
      signaling in cardiac fibroblasts is partially involved in myocardial MCP-1
      expression.

PMID- 14684426
TI  - Association of the human Y chromosome with cholesterol levels in the general
      population.
AB  - OBJECTIVE: Males are at higher risk of cardiovascular diseases than females. The
      aim of the study was to test whether the potential of the Y chromosome to affect
      cardiovascular risk could be attributed to its influence on lipids. METHODS AND
      RESULTS: 1288 Polish men (1157 subjects from young healthy cohort and 131
      individuals from middle-aged hypertensive population) were phenotyped for
      determinants of cardiovascular risk including BMI, blood pressures, lipids, and
      testosterone. Each subject was genotyped for the HindIII(+/-) polymorphism within
      the nonrecombining region of the Y chromosome. Men with the HindIII(-) variant
      exhibited significantly higher total cholesterol (TC) and low-density lipoprotein
      cholesterol (LDL) levels than subjects with the HindIII(+) genotype in both
      populations. The differences between the genotypes were 0.15 mmol/L (P=0.0107)
      and 0.45 mmol/L (P=0.0377) in TC and 0.15 mmol/L (P=0.0059) and 0.41 mmol/L
      (P=0.0432) in LDL among young apparently healthy men and middle-aged hypertensive
      men, respectively. The HindIII(+) was associated with a significant increase in
      blood pressure of the middle-aged men. Testosterone serum concentrations
      correlated positively with HDL-cholesterol levels, and this association was
      independent of the Y chromosome. CONCLUSIONS: The results indicate that a
      locus/loci on the Y chromosome may influence LDL levels, independent of
      testosterone levels.

PMID- 14684427
TI  - Incidence of fatal or repaired abdominal aortic aneurysm in relation to
      inflammation-sensitive plasma proteins.
AB  - Background- Inflammation is an important pathophysiological feature of abdominal
      aortic aneurysms (AAA). Whether elevated levels of inflammation-sensitive plasma
      proteins (ISPs) predict the long-term risk of fatal or repaired AAA is largely
      unknown. METHODS AND RESULTS: Five ISPs (fibrinogen, orosomucoid, alpha1
      antitrypsin, haptoglobin, and ceruloplasmin) were measured in 6075 healthy men,
      mean age 46.8+/-3.7 years. After a mean time of 19 years, 63 men had a fatal or
      surgically/endovascularly repaired AAA. Risk of treatment or death from future
      AAA was studied in relation to the ISPs. The risk of future AAA increased
      significantly with the number of elevated ISPs (ie, in the top quartile). The
      proportions with future AAA were 0.4%, 1.0%, 1.3%, and 2.3% for men with none,
      one, two, and > or =3 ISPs, respectively, in the top quartile (trend: P<0.0001).
      The corresponding odds ratios were 1.00 (reference), 1.9 (95% CI: 0.8 to 4.5),
      2.2 (0.9 to 5.5), and 3.2 (1.4 to 7.2), respectively, adjusted for age, screening
      year, smoking, cholesterol, triglycerides, systolic blood pressure and physical
      inactivity (trend: P=0.004). CONCLUSIONS: The incidence of fatal or repaired AAA
      is associated with the ISP levels. In this population-based study, elevated ISPs
      could be observed many years before the clinical manifestation of disease.

PMID- 14684428
TI  - 3.5 years of insulin therapy with insulin glargine improves in vivo endothelial
      function in type 2 diabetes.
AB  - OBJECTIVE: To determine long-term effects of insulin glargine on vascular
      function in patients with type 2 diabetes. METHODS AND RESULTS: A total of 49 in
      vivo endothelial function tests, intrabrachial artery infusions of endothelium
      dependent (acetylcholine [ACh]) and endothelium-independent (sodium nitroprusside
      [SNP]) vasoactive agents, were performed in 11 patients with type 2 diabetes
      (age: 59+/-2 years; BMI: 29.7+/-0.9 kg/m2; fasting plasma glucose: 226+/-14
      mg/dL) and 16 matched normal subjects. The tests in the type 2 diabetic patients
      were performed before and after 6 months and 3.5 years of combination therapy
      with insulin glargine and metformin. A control group of type 2 diabetic patients
      not treated with insulin was studied twice at 6-month intervals. Before
      treatment, blood flow during infusions of low and high doses of ACh were
      significantly lower in the type 2 diabetic patients than in the normal subjects
      (P=0.021 for ANOVA). In the patients with type 2 diabetes, blood flow during
      infusion of the low dose of ACh averaged 7.1+/-0.8 mL/dL per minute at baseline,
      8.8+/-1.0 mL/dL per minute at 6 months (NS), and then increased compared with
      baseline by 87+/-29% to 11.6+/-1.4 mL/dL per minute at 3.5 years (P<0.02 versus
      baseline). Blood flow during infusion of the high dose of ACh increased from
      8.8+/-0.9 at baseline to 13.0+/-1.9 mL/dL per minute at 6 months (P<0.05) and by
      86+/-25% to 14.7+/-1.6 mL/dL per minute at 3.5 years (P<0.01 versus baseline),
      which was not different from normal subjects. Blood flow during infusion of low
      (blood flow at 0 months: 7.7+/-0.5; at 6 months: 9.9+/-0.6; P<0.01 for 6 versus 0
      months; and 3.5 years: 11.6+/-1.1 mL/dL per minute; P<0.02 for 3.5 years versus 0
      months) and high (blood flow at 0 months: 10.7+/-0.9; 6 months: 13.4+/-1.0;
      P<0.05 for 6 versus 0 months; and 3.5 years: 16.6+/-1.5 mL/dL per minute; P<0.05
      for 3.5 years versus 0 months) doses of SNP also increased significantly during
      insulin therapy. CONCLUSIONS: We conclude that insulin glargine therapy improves
      endothelium-dependent and endothelium-independent vasodilatation. These data
      support the idea that long-term insulin therapy has beneficial rather than
      harmful effects on vascular function in type 2 diabetes.

PMID- 14684431
TI  - Synaptic plasticity and AMPA receptor trafficking.
AB  - Alterations in neuronal activity can elicit long-lasting changes in the strength
      of synaptic transmission at excitatory synapses and, as a consequence, may
      underlie many forms of experience-dependent plasticity, including learning and
      memory. The best-characterized forms of such synaptic plasticity are the long
      term depression (LTD) and long-term potentiation (LTP) observed at excitatory
      synapses in the CA1 region of the hippocampus. It is now well accepted that the
      trafficking of AMPA receptors to and away from the synaptic plasma membrane plays
      an essential role in both LTP and LTD, respectively. Here we review current
      models of AMPA receptor trafficking and how this trafficking may be regulated at
      the molecular level in order to produce the observed changes in synaptic
      strength. We also review recent work from our lab suggesting that synaptic
      plasticity in the mesolimbic dopamine system may contribute importantly to the
      neural adaptations elicited by drugs of abuse.

PMID- 14684432
TI  - Physiological roles and therapeutic potential of metabotropic glutamate
      receptors.
AB  - Discovery of mGlu receptors has dramatically influenced our understanding of
      glutamatergic neurotransmission in the central nervous system. This receptor
      family provides a mechanism by which activation by glutamate can regulate a
      number of important neuronal and glial functions that are not typically modulated
      by ligand-gated ion channels. This includes modulation of neuronal excitability,
      synaptic transmission, and various metabolic functions. Because of the ubiquitous
      distribution of glutamatergic synapses, discovery of the mGlu receptors
      immediately raised the likelihood that mGlu receptors would participate in most,
      if not all, major functions of the CNS. In addition, the wide diversity and
      heterogeneous distribution of mGlu receptor subtypes could provide an opportunity
      for development of pharmacological agents that selectively target specific CNS
      systems to achieve a therapeutic effect. Over the past decade, an increasing
      number of agonists and antagonists selective for specific mGlu receptor subtypes
      have been developed. Use of these pharmacological tools along with genetic
      approaches has led to major advances in our understanding of the roles of mGlu
      receptors in regulating CNS systems and animal behavior. These studies suggest
      that drugs active at mGlu receptors may be useful in treatment of a wide variety
      of neurological and psychiatric disorders.

PMID- 14684433
TI  - Genomics and variation of ionotropic glutamate receptors.
AB  - Sequencing of the human, mouse, and rat genomes has enabled a comprehensive
      informatics approach to gene families. This approach is informative for
      identification of new members of gene families, for cross-species sequence
      conservation related to functional conservation, for within-species diversity
      related to functional variation, and for historical effects of selection. This
      genome informatics approach also focuses our attention on genes whose genomic
      locations coincide with linkages to phenotypes. We are identifying ionotropic
      glutamate receptor (IGR) sequence variation by resequencing technologies,
      including denaturing high-performance liquid chromoatography (dHPLC), for
      screening and direct sequencing, and by information mining of public (e.g., dbSNP
      and ENSEMBL) and private (i.e., Celera Discovery System) sequence databases. Each
      of the 16 known IGRs is represented in these databases, their positions on a
      canonical physical map (for example, the Celera map) are established, and
      comparison to mouse and rat sequences has been performed, revealing substantial
      conservation of these genes, which are located on different chromosomes but found
      within syntenic groups of genes. A collection of 38 missense variants were
      identified by the informatics and resequencing approaches in several of these
      receptor genes, including GRIN2B, GRIN3B, GRIA2, GRIA3, and GRIK1. This
      represents only a fraction of the sequence variation across these genes, but, in
      fact, these may constitute a large fraction of the common polymorphisms at these
      genes, and these polymorphisms are a starting point for understanding the role of
      these receptors in neurogenetic variation. Genetically influenced human
      neurobehavioral phenotypes that are likely to be linked to IGR genetic variants
      include addictions, anxiety/dysphoria disorders, post-brain injury behavioral
      disorders, schizophrenia, epilepsy, pain perception, learning, and cognition.
      Thus, the effects of glutamate receptor variation may be protean, and the task of
      relating variation to behavior difficult. However, functional variants of (1)
      catechol-O-methyltransferase, (2) serotonin transporter, and (3) brain-derived
      neurotrophic factor have recently been linked both to behavioral differences and
      to intermediate phenotypes, suggesting a pathway by which functional variation at
      IGRs can be tied to an etiologically complex phenotype.

PMID- 14684434
TI  - Anatomical substrates for glutamate-dopamine interactions: evidence for
      specificity of connections and extrasynaptic actions.
AB  - For normal regulation of motor, affective, and cognitive functions, dopamine
      provides an essential modulation of glutamate transmission within multiple brain
      regions. This paper will review three principal anatomical substrates for such
      interactions. First, dopamine modulates the activity of glutamate neurons within
      the cerebral cortex. Evidence will be reviewed for dopamine regulation of
      pyramidal neurons in the prefrontal cortex via synaptic and extrasynaptic
      mechanisms and through indirect effects mediated by GABA cells. Second, glutamate
      neurons innervate dopamine cells within the ventral tegmental area. Evidence will
      be described for selective glutamate input from the prefrontal cortex or the
      brain stem tegmentum to different populations of dopamine cells. The third level
      of interaction occurs within target regions via convergent synaptic or
      extrasynaptic regulation of common neurons. Such convergence will be reviewed for
      the basal ganglia, prefrontal cortex, and amygdala. Together, these substrates
      for glutamate-dopamine interactions provide several mechanisms for normal
      regulation of brain function. Sites of modulatory interaction between dopamine
      and glutamate also suggest circuit alterations that might contribute to the
      pathophysiology of mental health disorders and provide potential sites for
      therapeutic intervention in these conditions.

PMID- 14684435
TI  - Electrophysiological interactions between striatal glutamatergic and dopaminergic
      systems.
AB  - Glutamatergic and dopaminergic systems play a primary role in frontal-subcortical
      circuits involved in motor and cognitive functions. Considerable evidence has
      emerged indicating that the complex interaction between these neurotransmitter
      systems within the dorsal striatum and nucleus accumbens is critically involved
      in the gating of information flow in these highly integrative brain regions. As a
      result, disruptions of the interaction between glutamate and dopamine has been
      proposed as a pathological basis for a number of disorders, including the
      pathophysiology of schizophrenia. In this chapter, we discuss recent studies that
      have significantly advanced our understanding of the reciprocal interactions
      between glutamatergic and dopaminergic systems within the striatal complex in the
      normal brain and in pathological states.

PMID- 14684436
TI  - Molecular abnormalities of the glutamate synapse in the thalamus in
      schizophrenia.
AB  - Schizophrenia has been associated with dysfunction of glutamatergic
      neurotransmission. Synaptic glutamate activates pre- and postsynaptic ionotropic
      NMDA, AMPA, and kainate and metabotropic receptors, is removed from the synapse
      via five cell surface-expressed transporters, and is packaged for release by
      three vesicular transporters. In addition, there is a family of intracellular
      molecules enriched in the postsynaptic density (PSD) that target glutamate
      receptors to the synaptic membrane, modulate receptor activity, and coordinate
      glutamate receptor-related signal transduction. Each family of PSD proteins is
      selective for a given glutamate receptor subtype, the most well characterized
      being the NMDA receptor binding proteins PSD93, PSD95, NF-L, and SAP102. Besides
      binding glutamate receptors, many of these proteins also interact with cell
      surface proteins like cell adhesion molecules, ion channels, cytoskeletal
      elements, and signal transduction molecules. Given the complexity of the
      glutamate neurotransmitter system, there are many locations where disruption of
      normal signaling could occur and give rise to abnormal glutamatergic
      neurotransmission in schizophrenia. Using multiple cohorts of postmortem tissue,
      we have examined these synaptic molecules in schizophrenic thalamus. The
      expression of NR1 and NR2C subunit transcripts is decreased in the thalamus in
      schizophrenia. Interestingly, three intracellular PSD molecules that link the
      NMDA receptor to signal transduction pathways are also abnormally expressed.
      Additionally, several of the cell surface and vesicular transporters are abnormal
      in the schizophrenic thalamus. While occasional findings of abnormal receptor
      expression are made, the most dramatic and consistent alterations that we have
      found in the thalamus in schizophrenia involve the family of intracellular
      signaling/scaffolding molecules. We propose that schizophrenia has a
      glutamatergic component that involves alterations in the intracellular machinery
      that is coupled to glutamate receptors, in addition to abnormalities of the
      receptors themselves. Our data suggest that schizophrenia is associated with
      abnormal glutamate receptor-related intracellular signaling in the thalamus, and
      point to novel targets for innovative drug discovery.

PMID- 14684437
TI  - Glutamate receptors and transporters in the hippocampus in schizophrenia.
AB  - Postmortem studies, using various methods and directed at several molecular
      targets, have provided increasing evidence that glutamatergic neurotransmission
      is affected in schizophrenia. The bulk of the data are in the hippocampus,
      wherein there is reduced expression of one or more subunits for all three
      ionotropic receptors (NMDA, AMPA, and kainate). Presynaptic glutamatergic
      markers, notably the vesicular glutamate transporter VGLUT1, may also be
      decreased in schizophrenia, especially in older subjects. CA1 appears less
      affected than other subfields, and the decrements may be greater in the left than
      in the right hippocampus. The recently described susceptibility genes for
      schizophrenia all act upon glutamatergic synaptic transmission, which may,
      therefore, be part of the core pathophysiology of the disorder.

PMID- 14684438
TI  - Altered cortical glutamate neurotransmission in schizophrenia: evidence from
      morphological studies of pyramidal neurons.
AB  - Multiple lines of evidence from pharmacological, neuroimaging, and postmortem
      studies implicate disturbances in cortical glutamate neurotransmission in the
      pathophysiology of schizophrenia. Given that pyramidal neurons are the principal
      source of cortical glutamate neurotransmission, as well as the targets of the
      majority of cortical glutamate-containing axon terminals, understanding the
      nature of altered glutamate neurotransmission in schizophrenia requires an
      appreciation of both the types of pyramidal cell abnormalities and the specific
      class(es) of pyramidal cells that are affected in the illness. In this chapter,
      we review evidence indicating that a subpopulation of pyramidal neurons in the
      dorsolateral prefrontal cortex exhibits reductions in dendritic spine density, a
      marker of the number of excitatory inputs, and in somal volume, a measure
      correlated with a neuron's dendritic and axonal architecture. Specifically,
      pyramidal neurons located in deep layer 3 of the dorsolateral prefrontal cortex
      and that lack immunoreactivity for nonphosphorylated neurofilament protein may be
      particularly involved in the pathophysiology of schizophrenia. The presence of
      similar changes in pyramidal neurons located in deep layer 3 of auditory
      association cortex suggests that a shared property, which remains to be
      determined, confers cell type-specific vulnerability to a subpopulation of
      cortical glutamatergic neurons in schizophrenia.

PMID- 14684439
TI  - Evaluating glutamatergic transmission in schizophrenia.
AB  - Our findings with schizophrenia and the glutamate system have relied on the
      characterization of the clinical response of patients to ketamine and their
      functional brain imaging response (rCBF) to the drug. Prior to the human studies
      reported here, we had evaluated the region activation characteristics and
      pharmacology of PCP and its congener MK 801 in animals. What I will report in
      this paper has been individually reported elsewhere but brought together here in
      a new synthesis.

PMID- 14684440
TI  - The NMDA receptor hypofunction model of psychosis.
AB  - Antagonists of the NMDA glutamate receptor, including phencyclidine (PCP),
      ketamine, and CGS-19755, produce cognitive and behavioral changes in humans. In
      rodents these agents produce a myriad of histopathological and neurochemical
      changes. Several lines of evidence suggest that a large number of these drug
      induced effects are dose-dependent manifestations of the same general
      disinhibition process in which NMDA antagonists abolish GABAergic inhibition,
      resulting in the simultaneous excessive release of acetylcholine and glutamate.
      Progressive increases in the severity of NMDA receptor hypofunction (NRHypo)
      within the brain produce an increasing range of effects on brain function.
      Underexcitation of NMDA receptors, induced by even relatively low doses of NMDA
      antagonist drugs, can produce specific forms of memory dysfunction without
      clinically evident psychosis. More severe NRHypo can produce a clinical syndrome
      very similar to a psychotic schizophrenic exacerbation. Finally, sustained and
      severe NRHypo in the adult brain is associated with a form of neurotoxicity with
      well-characterized neuropathological features. In this paper several of these
      effects of NMDA antagonists and a likely mechanism responsible for producing them
      will be reviewed. In addition the possible role of NRHypo in the pathophysiology
      of idiopathic psychotic disorders will be considered.

PMID- 14684441
TI  - Glutamatergic animal models of schizophrenia.
AB  - Several lines of evidence, including recent genetic linkage studies implicating
      susceptibility genes for schizophrenia, make a strong case that abnormal NMDA
      receptor-mediated neurotransmission is a major locus for the pathophysiology of
      schizophrenia. Animal models that are relevant to putative NMDA dysfunction in
      schizophrenia have excellent face validity for several symptoms of schizophrenia
      and are important tools for the design of novel pharmacological intervention in
      schizophrenia. The present chapter includes a brief review of the utility of
      these models and the search for new medications that have the potential of
      normalizing glutamate neurotransmission in schizophrenia.

PMID- 14684442
TI  - Glutamate, dopamine, and schizophrenia: from pathophysiology to treatment.
AB  - The fundamental pathological process(es) associated with schizophrenia remain(s)
      uncertain, but multiple lines of evidence suggest that this condition is
      associated with (1) excessive stimulation of striatal dopamine (DA) D2 receptors,
      (2) deficient stimulation of prefrontal DA D1 receptors and, (3) alterations in
      prefrontal connectivity involving glutamate (GLU) transmission at N-methyl-d
      aspartate (NMDA) receptors. This chapter first briefly discusses the current
      knowledge status for these abnormalities, with emphasis on results derived from
      clinical molecular imaging studies. The evidence for hyperstimulation of striatal
      D2 receptors rests on strong pharmacological evidence and has recently received
      support from brain imaging studies. The hypothesis of deficient prefrontal cortex
      (PFC) D1 receptor stimulation is almost entirely derived from preclinical
      studies. Preliminary imaging data compatible with this hypothesis have recently
      emerged. The NMDA hypofunction hypothesis originates mainly from indirect
      pharmacological data. The interactions between DA and GLU systems relevant to
      schizophrenia are then reviewed. Animal and imaging data supporting the general
      model that the putative DA imbalance in schizophrenia (striatal excess and
      cortical deficiency) might be secondary to NMDA hypofunction in the PFC and its
      connections are presented. Equally important are the potential consequences of
      this DA imbalance for NMDA function in the striatum and the cortex, which are
      subsequently discussed. In conclusion, it is proposed that schizophrenia is
      associated with strongly interconnected abnormalities of GLU and DA transmission:
      NMDA hypofunction in the PFC and its connections might generate a pattern of
      dysregulation of DA systems that, in turn, further weakens NMDA-mediated
      connectivity and plasticity.

PMID- 14684443
TI  - Glutamate-mediated plasticity in corticostriatal networks: role in adaptive motor
      learning.
AB  - Little is known about how memories of new voluntary motor actions, also known as
      procedural memory, are formed at the molecular level. Our work examining
      acquisition of lever-pressing for food in rats has shown that activation of
      glutamate NMDA receptors, within broadly distributed but interconnected regions
      (e.g., nucleus accumbens core, prefrontal cortex, basolateral amygdala), is
      critical for such learning to occur. This receptor stimulation triggers
      intracellular cascades that involve protein phosphorylation and new protein
      synthesis. In support of this idea, we have found that posttrial inhibition of
      protein synthesis in the ventral striatum impairs learning, whereas posttrial
      NMDA receptor blockade does not. More recent data show extension of this network
      to the central amygdala, where infusions of NMDA antagonists also impair
      learning. We hypothesize that activity in this distributed network (including
      dopaminergic activity and perhaps muscarinic cholinergic activity) computes
      coincident events and thus enhances the probability that temporally related
      actions and events (e.g., lever pressing and delivery of reward) become
      associated. Such basic mechanisms of plasticity within this reinforcement
      learning network also appear to be profoundly affected in addiction.

PMID- 14684444
TI  - Glutamate transmission and addiction to cocaine.
AB  - A variety of data point to the possibility that neuroadaptations in glutamate
      transmission are produced by repeated exposure to cocaine that result in the
      expression of behaviors characteristic of addiction, such as craving and relapse.
      Using the reinstatement model of relapse in rats, glutamate release in the
      projection from the prefrontal cortex to the nucleus accumbens has been shown to
      underlie cocaine- and stress-primed reinstatement. In this report, four
      adaptations produced by withdrawal from repeated cocaine are described that may
      regulate the release of glutamate underlying reinstatement of drug-seeking
      resulted. (1) Neurons in the prefrontal cortex have increased levels of activator
      of G protein signaling 3 (AGS3) that causes reduced signaling through Gi coupled
      receptors, and normalization of AGS3 blocked cocaine-primed reinstatement. (2)
      The activity of the cystine-glutamate exchanger is reduced resulting in decreased
      extracellular glutamate in the nucleus accumbens, and normalization of exchanger
      activity prevented cocaine-primed reinstatement. (3) Metobotropic glutamate
      receptor function is diminished after repeated cocaine administration that
      results in reduced regulation of glutamate release. (4) Homer1 protein is reduced
      in the nucleus accumbens, and Homer2 knockout mice show enhanced responsiveness
      to cocaine. Taken together, there appears to be both pre- and postsynaptic
      changes in glutamate transmission that dysregulates the glutamatergic projection
      from the prefrontal cortex to the nucleus accumbens. These adaptations are
      hypothesized to facilitate glutamate release in response to a cocaine injection
      or acute stress and lead to the reinstatement of drug-seeking behavior.

PMID- 14684445
TI  - NMDA receptor antagonism and the ethanol intoxication signal: from alcoholism
      risk to pharmacotherapy.
AB  - This paper reviews clinical evidence suggesting that antagonism of the N-methyl-D
      aspartate subtype of glutamate receptors by ethanol may convey an important
      component of the ethanol intoxication signal, that is, subjective and objective
      responses associated with the consumption of a large amount of ethanol. It will
      then review recent evidence that two phenotypes associated with increased risk
      for heavy alcohol consumption, recovering ethanol-dependent patients, and healthy
      individuals with a family history of alcohol dependence, exhibit reduced
      sensitivity to the dysphoric consequences of administration of the NMDA receptor
      antagonist, ketamine. Each of these groups displays reduced sensitivity to a
      potentially important response that might normally trigger the cessation of
      ethanol consumption. These data raise the possibility that alterations in NMDA
      receptor function that reduce the response to the NMDA antagonist component of
      ethanol may increase the risk for heavy drinking. This hypothesis is consistent
      with growing evidence that NMDA receptor antagonists may play a role in the
      treatment of alcoholism by suppressing alcohol withdrawal, reducing the
      development or expression of alcohol tolerance, or preventing or reversing the
      sensitiziation to ethanol effects.

PMID- 14684446
TI  - Short- and long-term modulation of synaptic inputs to brain reward areas by
      nicotine.
AB  - Dopamine signaling in brain reward areas is a key element in the development of
      drug abuse and dependence. Recent anatomical and electrophysiological research
      has begun to elucidate both complexity and specificity in synaptic connections
      between ventral tegmental neurons and their inputs. Specifically, the activity of
      dopamine neurons in the ventral tegmental area relies on the combination of both
      excitatory and inhibitory inputs. Controlling endogenous neurotransmission to
      dopamine neurons is one mechanism by which drugs of abuse affect both transient
      and long-term changes in synaptic activity. Here, we review recent findings
      concerning glutamatergic, GABAergic, and cholinergic inputs to dopamine neurons,
      and their roles in the reinforcement associated with drug abuse. Importantly,
      several studies support that a single drug exposure can lead to changes in
      synaptic strength that are associated with learning and memory. Ultimately, these
      cellular changes could underlie the long-lasting effects of drugs. Furthermore,
      nicotinic acetylcholine receptors in the ventral tegmental area emerge as a
      possible common target for the behavioral and cellular actions not only of
      nicotine, but also of several other drugs of abuse. Finally, we explore age
      related differences in nicotine sensitivity in order to understand both human
      epidemiological data, and laboratory animal behavioral findings that suggest
      adolescents are more susceptible to developing nicotine dependence.

PMID- 14684447
TI  - Glutamatergic transmission in opiate and alcohol dependence.
AB  - Both the nucleus accumbens (NAcc) and central amygdala (CeA) are thought to play
      roles in tolerance to, and dependence on, abused drugs. Although our past studies
      in rat brain slices suggested a role for NMDA receptors (NMDARs) in NAcc neurons
      in the effects of acute and chronic opiate treatment, the cellular and molecular
      mechanisms remained unclear. Therefore, we examined the effects of morphine
      dependence on electrophysiological properties of NMDARs in freshly isolated NAcc
      neurons and on expression of mRNA coding for NR2A-C subunits using single-cell RT
      PCR. Chronic morphine did not alter the affinity for NMDAR agonists glutamate,
      homoquinolinate, or NMDA, but decreased the affinity of the coagonist glycine.
      Chronic morphine altered the NMDAR inhibition by two NMDAR antagonists, 7-Cl
      kynurenate and ifenprodil, but not that by d-APV or Mg2+. Chronic morphine
      accelerated the NMDA current desensitization rate in NAcc neurons. In single-cell
      RT-PCR, chronic morphine predominantly reduced the number of neurons expressing
      multiple NR2 subunits. Ethanol also alters NMDARs. We found that low ethanol
      concentrations (IC50 = 13 mM) inhibited NMDA currents and NMDA-EPSPs in most NAcc
      neurons in a slice preparation. NAcc neurons from ethanol-dependent rats showed
      enhanced NMDA sensitivity. In CeA neurons, acute ethanol decreased (by 10-25%)
      non-NMDA- and NMDA-EPSPs in most neurons. In CeA neurons from ethanol-dependent
      rats, acute ethanol decreased the non-NMDA-EPSPs to the same extent as in naive
      rats, but inhibited (by 30-40%) NMDA-EPSPs significantly more than in controls,
      suggesting sensitization to ethanol. Preliminary studies with microdialysis and
      real-time PCR analysis support this idea: local ethanol administration in vivo
      had no effect on glutamate release, but chronic ethanol nearly tripled the
      expression of NR2B subunits (the most ethanol sensitive) in CeA. These combined
      findings suggest that changes in glutamatergic transmission in NAcc and CeA may
      underlie the neuroadaptions that lead to opiate and ethanol dependence.

PMID- 14684449
TI  - Plastic control of striatal glutamatergic transmission by ensemble actions of
      several neurotransmitters and targets for drugs of abuse.
AB  - Long-lasting alterations in the efficacy of glutamatergic synapses, such as long
      term potentiation (LTP) and long-term depression (LTD), are prominent models for
      mechanisms of information storage in the brain. It has been suggested that
      exposure to drugs of abuse produces synaptic plasticity at glutamatergic synapses
      that shares many features with LTP and LTD, and that these synaptic changes may
      play roles in addiction. We have examined the involvement of particular
      neurotransmitters in synaptic plasticity at glutamatergic synapses within the
      striatum, a brain region with prominent roles in initiation and sequencing of
      actions, as well as habit formation. Our studies indicate that multiple
      neurotransmitters interact to produce striatal synaptic plasticity, and that the
      relative strength and patterning of the afferent inputs that release the various
      neurotransmitters determines whether LTP or LTD is activated. Drugs of abuse
      interact with glutamatergic synaptic plasticity in multiple ways, including
      alterations in dopamine release and more direct effects on glutamate release and
      glutamate receptors. We hypothesize that these effects contribute to addiction by
      facilitating the formation of new, drug-centered habits, and by disruption of
      more adaptive behaviors.

PMID- 14684448
TI  - Exogenous and endogenous cannabinoids control synaptic transmission in mice
      nucleus accumbens.
AB  - Addictive drugs are thought to alter normal brain function and cause the
      remodeling of synaptic functions in areas important to memory and reward.
      Excitatory transmission to the nucleus accumbens (NAc) is involved in the actions
      of most drugs of abuse, including cannabis. We have explored the functions of the
      endocannabinoid system at the prefrontal cortex-NAc synapses. Immunocytochemistry
      showed cannabinoid receptor (CB1) expression on axonal terminals making contacts
      with NAc neurons. In NAc slices, synthetic cannabinoids inhibit spontaneous and
      evoked glutamate-mediated transmission through presynaptic activation of
      presynaptic K+ channels and GABA-mediated transmission most likely via a direct
      presynaptic action on the vesicular release machinery. How does synaptic activity
      lead to the production of endogenous cannabinoids (eCBs) in the NAc? More
      generally, do eCBs participate in long-term synaptic plasticity in the brain? We
      found that tetanic stimulation (mimicking naturally occurring frequencies) of
      prelimbic glutamatergic afferents induced a presynaptic LTD dependent on eCB and
      CB1 receptors (eCB-LTD). Induction of eCB-LTD required postsynaptic activation of
      mGlu5 receptors and a rise in postsynaptic Ca2+ from ryanodine-sensitive
      intracellular Ca2+ stores. This retrograde signaling cascade involved
      postsynaptic eCB release and activation of presynaptic CB1 receptors. In the NAc,
      eCB-LTD might be part of a negative feedback loop, reducing glutamatergic
      synaptic strength during sustained cortical activity. The fact that this new form
      of LTD was occluded by an exogenous cannabinoid suggested that cannabis
      derivatives, such as marijuana, may alter normal eCB-mediated synaptic
      plasticity. These data suggest a major role of the eCB system in long-term
      synaptic plasticity and give insights into how cannabis derivatives, such as
      marijuana, alter normal eCB functions in the brain reward system.

PMID- 14684450
TI  - Mechanisms by which dopamine receptors may influence synaptic plasticity.
AB  - While dopamine (DA) receptors mediate acute effects of amphetamine and cocaine,
      chronic drug administration produces many glutamate-dependent adaptations,
      including LTP in reward-related neuronal circuits. An important question presents
      itself: How do DA receptors influence glutamate-dependent synaptic plasticity?
      Alterations in AMPA receptor phosphorylation and trafficking are critical for
      LTP. We hypothesize that D1 DA receptors modulate these processes, that chronic
      drug-induced adaptations in D1 receptor signaling, therefore, trigger
      compensatory changes in AMPA receptor function, and that this ultimately
      contributes to inappropriate plasticity in addiction-related neuronal circuits.
      Postnatal rat nucleus accumbens (NAc) cultures were used to study D1 receptor
      regulation of the AMPA receptor subunit GluR1. We found that D1 receptor
      stimulation enhances phosphorylation of GluR1 at the protein kinase A (PKA) site.
      Furthermore, D1 receptor stimulation increases GluR1 surface expression by
      increasing the rate of GluR1 externalization. The latter effect is prevented by
      the PKA inhibitors KT5720 and RpcAMPS, whereas the PKA activator SpcAMPS
      increases the rate of GluR1 externalization. These findings indicate that PKA
      phosphorylation is important in determining AMPA receptor surface expression and
      suggest a mechanism by which DA-releasing drugs of abuse may directly tap into
      fundamental mechanisms that enable synaptic plasticity. A limitation of our
      current model is that there are no intrinsic glutamate neurons in the NAc and
      thus no glutamate synapses in NAc cultures. To address this problem, we have
      restored excitatory synaptic inputs to NAc neurons by co-culturing them with
      prefrontal cortex (PFC) neurons. We are also studying GluR1 trafficking in PFC
      cultures. In both systems, synaptic AMPA receptors can be defined based on
      colocalization of GluR1 and the synaptic marker synaptobrevin. Preliminary
      results suggest that D1 receptor stimulation or PKA activation leads to increased
      surface GluR1 expression in PFC neurons but not to insertion into synaptic sites.

PMID- 14684451
TI  - Glutamate and depression: clinical and preclinical studies.
AB  - The past decade has seen a steady accumulation of evidence supporting a role for
      the excitatory amino acid (EAA) neurotransmitter, glutamate, and its receptors in
      depression and antidepressant activity. To date, evidence has emerged indicating
      that N-methyl-d-aspartate (NMDA) receptor antagonists, group I metabotropic
      glutamate receptor (mGluR1 and mGluR5) antagonists, as well as positive
      modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      receptors have antidepressant-like activity in a variety of preclinical models.
      Moreover, antidepressant-like activity can be produced not only by drugs
      modulating the glutamatergic synapse, but also by agents that affect subcellular
      signaling systems linked to EAA receptors (e.g., nitric oxide synthase). In view
      of the extensive colocalization of EAA and monoamine markers in nuclei such as
      the locus coeruleus and dorsal raphe, it is likely that an intimate relationship
      exists between regulation of monoaminergic and EAA neurotransmission and
      antidepressant effects. Further, there is also evidence implicating disturbances
      in glutamate metabolism, NMDA, and mGluR1,5 receptors in depression and
      suicidality. Finally, recent data indicate that a single intravenous dose of an
      NMDA receptor antagonist is sufficient to produce sustained relief from
      depressive symptoms. Taken together with the proposed role of neurotrophic
      factors in the neuroplastic responses to stressors and antidepressant treatments,
      these findings represent exciting and novel avenues to both understand depressive
      symptomatology and develop more effective antidepressants.

PMID- 14684452
TI  - Regulation of cellular plasticity cascades in the pathophysiology and treatment
      of mood disorders: role of the glutamatergic system.
AB  - There is increasing evidence from a variety of sources that mood disorders are
      associated with regional reductions in brain volume, as well as reductions in the
      number, size, and density of glia and neurons in discrete brain areas. Although
      the precise pathophysiology underlying these morphometric changes remains to be
      fully elucidated, the data suggest that severe mood disorders are associated with
      impairments of structural plasticity and cellular resilience. In this context, it
      is noteworthy that a growing body of data suggests that the glutamatergic system-
      which is known to play a major role in neuronal plasticity and cellular
      resilience--may be involved in the pathophysiology and treatment of mood
      disorders. Preclinical studies have shown that the glutamatergic system
      represents targets (often indirect) for the actions of antidepressants and mood
      stabilizers. There are a number of glutamatergic "plasticity enhancing"
      strategies that may be of considerable utility in the treatment of mood
      disorders. Among the most immediate ones are NMDA antagonists, inhibitors of
      glutamate-release agents, and AMPA potentiators; this research progress holds
      much promise for the development of novel therapeutics for the treatment of
      severe, refractory mood disorders.

PMID- 14684453
TI  - Clinical studies implementing glutamate neurotransmission in mood disorders.
AB  - Emerging evidence suggests that the amino acid neurotransmitter systems are
      associated with the pathophysiology and treatment of mood disorders. Recent
      advances in the areas of molecular neurobiology, pharmacology, and magnetic
      resonance spectroscopy (MRS) now provide better tools to probe the function of
      the amino acid neurotransmitter systems and are affording us the opportunity to
      better investigate the relationship of these systems to mood disorders. Here we
      review the available literature in the field and suggest a possible
      pathophysiological model that may account for the many of the findings.

PMID- 14684454
TI  - A role for noradrenergic transmission in the actions of phencyclidine and the
      antipsychotic and antistress effects of mGlu2/3 receptor agonists.
AB  - Evidence suggests that glutamatergic neuronal transmission is involved in
      psychiatric and neurological disorders and that drugs that target glutamate
      systems may serve as novel therapeutics in humans. For example, agonists for
      group II mGlu receptors (mGlu2 and mGlu3) have been shown to be anxiolytic in
      certain animal models and have shown promise in early human trials. mGlu2/3
      receptor agonists also block the neurochemical and behavioral actions of
      psychotogens, such as phencyclidine and amphetamine in rodents, suggesting that
      they may be useful to treat psychosis in humans. Recently, we have used in vivo
      microdialysis and behavioral methods to further explore the potential
      antipsychotic and antistress actions of mGlu2/3 receptor agonists in rats. In
      subjects undergoing brain microdialysis of the nucleus accumbens shell, we have
      shown that LY379268 (3 mg/kg s.c.) (a systemically active mGlu2/3 receptor
      agonist) blocks PCP-induced locomotor activations for approximately 3 hours. In
      these animals, PCP-induced dopamine release was reduced, but only in a transient
      fashion (15-75 min). PCP-induced norepinephrine release was also reduced, but
      unlike dopamine, in a manner that was temporally correlated with the reduction of
      PCP-induced behaviors. In separate experiments in rats not undergoing
      microdialysis, the alpha2-adrenergic receptor agonist, clonidine, was shown to
      block PCP behaviors, and the norepinephrine reuptake inhibitor reboxetine was
      shown to exacerbate PCP-induced ambulations. In the latter study, LY379268
      pretreatment effectively reversed the PCP behaviors in both control and
      reboxetine-treated animals. These data support a role for noradrenergic
      neurotransmission in the actions of drugs such as phencyclidine and suggest that
      stress pathways associated with these drugs can be normalized by mGlu2/3 receptor
      activation.

PMID- 14684455
TI  - Converging evidence of NMDA receptor hypofunction in the pathophysiology of
      schizophrenia.
AB  - Numerous clinical studies demonstrate that subanesthetic doses of dissociative
      anesthetics, which are noncompetitive antagonists at the NMDA receptor, replicate
      in normal subjects the cognitive impairments, negative symptoms, and brain
      functional abnormalities of schizophrenia. Postmortem and genetic studies have
      identified several abnormalities associated with schizophrenia that would
      interfere with the activation of the glycine modulatory site on the NMDA
      receptor. Placebo-controlled clinical trials with agents that directly or
      indirectly activate the glycine modulatory site consistently reduce negative
      symptoms and frequently improve cognition in patients with chronic schizophrenia
      who are receiving concurrent typical antipsychotics. Thus, there is convincing
      evidence that hypofunction of a subset of NMDA receptors may contribute to the
      symptomatic features of schizophrenia.

PMID- 14684456
TI  - Glutamatergic agents for cocaine dependence.
AB  - Effective medications for cocaine dependence are needed to improve outcome in
      this chronic, relapsing disorder. Medications affecting glutamate function are
      reasonable candidates for investigation, given the involvement of glutamate
      circuits in reward-related brain regions and evidence of cocaine-induced
      glutamatergic dysregulation. In addition, it is increasingly apparent that
      glutamatergic mechanisms underlie several clinical aspects of cocaine dependence,
      including euphoria, withdrawal, craving, and hedonic dysfunction. Even denial,
      traditionally viewed as purely psychological, may result, in part, from
      dysfunctional glutamate-rich cortical regions. We review the involvement of
      glutamate in reward-related circuits, the acute and chronic effects of cocaine on
      these pathways, and glutamatergic mechanisms that contribute to the neurobiology
      of cocaine dependence. We also present preliminary data from our research of
      modafinil, a glutamate-enhancing agent with promise in the treatment of cocaine
      addicted individuals.

PMID- 14684457
TI  - Dopamine-acetylcholine interactions in the modulation of glutamate release.

PMID- 14684459
TI  - AMPA- and NMDA-associated postsynaptic protein expression in the human
      dorsolateral prefrontal cortex.

PMID- 14684458
TI  - N-acetyl cysteine-induced blockade of cocaine-induced reinstatement.

PMID- 14684460
TI  - AGS3: a G-Protein regulator of addiction-associated behaviors.

PMID- 14684461
TI  - Changes in electrophysiological properties of nucleus accumbens neurons depend on
      the extent of behavioral sensitization to chronic methamphetamine.

PMID- 14684462
TI  - Evaluation of NMDA receptors in vivo in schizophrenic patients with [123I]CNS
      1261 and SPET: preliminary findings.

PMID- 14684463
TI  - Effects of naloxone-precipitated morphine withdrawal on glutamate-mediated
      signaling in striatal neurons in vitro.

PMID- 14684465
TI  - Expression of ARHGEF11 mRNA in schizophrenic thalamus.

PMID- 14684466
TI  - Structurally dissimilar antimanic agents modulate synaptic plasticity by
      regulating AMPA glutamate receptor subunit GluR1 synaptic expression.
AB  - A growing body of data from clinical and preclinical studies suggests that the
      glutamatergic system may represent a novel therapeutic target for severe
      recurrent mood disorders. Since synapse-specific glutamate receptor
      expression/localization is known to play critical roles in synaptic plasticity,
      we investigated the effects of mood stabilizers on AMPA receptor expression. Rats
      were treated chronically with lithium or valproate, hippocampal synaptosomes were
      isolated, and GluR1 levels were determined. Additionally, hippocampal neurons
      were prepared from E18 rat embryos and treated with lithium or valproate. Surface
      expression of GluR1 was determined using a biotinylation assay, and double
      immunostaining with anti-GluR1 and anti-synaptotagmin antibodies was used to
      determine synaptic GluR1 levels. The AMPA receptor subunit GluR1 expression in
      hippocampal synaptosomes was significantly reduced by both chronic lithium and
      valproate. Overall, these studies show that AMPA receptor subunit GluR1 is a
      common target for two structurally highly dissimilar, but highly efficacious,
      mood stabilizers, lithium and valproate. These studies suggest that regulation of
      glutamatergically mediated synaptic plasticity may play a role in the treatment
      of mood disorders, and raise the possibility that agents more directly affecting
      synaptic GluR1 may represent novel therapies for this devastating illness.

PMID- 14684464
TI  - Opposite effects of GluR1 and PKA-resistant GluR1 overexpression in the ventral
      tegmental area on cocaine reinforcement.

PMID- 14684467
TI  - Cocaine-induced expression differences in glutamate receptor subunits and
      transporters in amygdalae of taste aversion-prone and taste aversion-resistant
      rats.

PMID- 14684469
TI  - Rapid AMPAR/NMDAR response to amphetamine: a detectable increase in AMPAR/NMDAR
      ratios in the ventral tegmental area is detectable after amphetamine injection.

PMID- 14684471
TI  - Altered prefrontal cortex-nucleus accumbens information processing in a
      developmental animal model of schizophrenia.

PMID- 14684470
TI  - Nucleus accumbens Homer proteins regulate behavioral sensitization to cocaine.

PMID- 14684472
TI  - Lithium regulates total and synaptic expression of the AMPA glutamate receptor
      GluR2 in vitro and in vivo.

PMID- 14684468
TI  - Cocaine-induced expression differences in PSD-95/SAP-90-associated protein 4 and
      in Ca2+/calmodulin-dependent protein kinase subunits in amygdalae of taste
      aversion-prone and taste aversion-resistant rats.

PMID- 14684473
TI  - Prefrontal group II metabotropic glutamate receptor activation decreases
      performance on a working memory task.

PMID- 14684474
TI  - The effects of selective orbitofrontal cortex lesions on the acquisition and
      performance of cue-controlled cocaine seeking in rats.

PMID- 14684475
TI  - In vivo characterization of changes in glycine levels induced by GlyT1
      inhibitors.

PMID- 14684478
TI  - Glutamate/monoamine interactions in the limbic thalamus.

PMID- 14684477
TI  - Elucidation of Homer 1a function in the nucleus accumbens using adenovirus gene
      transfer technology.

PMID- 14684476
TI  - Metabotropic glutamate 5 receptor antagonist MPEP decreased nicotine and cocaine
      self-administration but not nicotine and cocaine-induced facilitation of brain
      reward function in rats.

PMID- 14684479
TI  - Changes in NMDA receptor subunit mRNAs and cyclophilin mRNA during development of
      the human hippocampus.

PMID- 14684480
TI  - Blockade of the GlyT1 glycine transporter prolongs response to VTA stimulation in
      nucleus accumbens neurons.

PMID- 14684481
TI  - Modulation of inhibitory transmission in the rat globus pallidus by activation of
      mGluR4.

PMID- 14684482
TI  - Expression of transcripts for the vesicular glutamate transporters in the human
      medial temporal lobe.

PMID- 14684483
TI  - Metabotropic glutamate receptor regulation of extracellular glutamate levels in
      the prefrontal cortex.

PMID- 14684484
TI  - Cystine/glutamate antiporter regulation of vesicular glutamate release.

PMID- 14684485
TI  - Expression of the NR3A subunit of the NMDA receptor in human fetal brain.

PMID- 14684486
TI  - Coupling of glutamatergic neurotransmission and neuronal glucose oxidation over
      the entire range of cerebral cortex activity.

PMID- 14684487
TI  - Real time in vivo measures of L-glutamate in the rat central nervous system using
      ceramic-based multisite microelectrode arrays.

PMID- 14684488
TI  - TRH and related peptides: homeostatic regulators of glutamate transmission?

PMID- 14684489
TI  - L-homocysteine sulfinic acid and L-homocysteic acid stimulate phosphoinositide
      hydrolysis in rat cortical neurons.

PMID- 14684490
TI  - Distinct contributions of glutamate receptor subtypes to cognitive set-shifting
      abilities in the rat.

PMID- 14684491
TI  - Evidence for a relationship between Group 1 mGluR hypofunction and increased
      cocaine and ethanol sensitivity in Homer2 null mutant mice.

PMID- 14684492
TI  - Bidirectional modulation of cystine/glutamate exchanger activity in cultured
      cortical astrocytes.

PMID- 14684494
TI  - Modulation of excitatory transmission onto midbrain dopaminergic neurons of the
      rat by activation of group III metabotropic glutamate receptors.

PMID- 14684493
TI  - Dopamine-glutamate interactions in the control of cell excitability in medial
      prefrontal cortical pyramidal neurons from adult rats.

PMID- 14684495
TI  - Difference in mGluR5 interaction between positive allosteric modulators from two
      structural classes.

PMID- 14684497
TI  - The EUROCARE Study: strengths, limitations and perspectives of population-based,
      comparative survival studies.

PMID- 14684498
TI  - The EUROCARE-3 database: methodology of data collection, standardisation, quality
      control and statistical analysis.
AB  - The EUROCARE database contains data on 6.5 million cancer patients diagnosed from
      1978 to 1994 in populations covered by 67 cancer registries in 22 European
      countries. The quality-checked entries specify age, sex, diagnosis date, cancer
      site, morphology, microscopic confirmation and vital status, as well as
      containing broad indicators of stage. For EUROCARE-3, which refers to diagnoses
      from 1990 to 1994, 3389 cases with major data problems and 142,525 second or
      subsequent cancers were removed, leaving more than 2 million cases for analysis.
      From these data, observed and relative survival for each cancer site and country
      were calculated at 1, 3 and 5 years from diagnosis. Overall European survival for
      each cancer site and for all cancers combined were calculated combining country
      specific survival figures. Overall, 1.1% of cases were lost to follow-up, 4.2%
      were known from death certificates only and 1.2% were known at autopsy only. The
      percentage of microscopically confirmed cases varied with cancer site and
      country, and was always higher in northern European countries. Comparison of
      quality indicators for the EUROCARE-3 database with earlier EUROCARE databases
      indicates that data quality and standardisation have improved.

PMID- 14684499
TI  - Life expectancy and cancer survival in the EUROCARE-3 cancer registry areas.
AB  - BACKGROUND: Mortality information is essential for estimating relative cancer
      survival (that excludes deaths from other causes). However, sufficiently detailed
      mortality data are not available for all areas covered by the cancer registries
      (CRs) participating in the EUROCARE-3 study. MATERIALS AND METHODS: Mathematical
      methods were used to construct complete local mortality data (life tables) for
      each year of age (0-99), for each year (1978-2000) and by sex, from the
      incomplete life tables provided by CRs, presenting the results as life expectancy
      at birth (LE). Socio-economic data were obtained from the United Nations (UN) and
      Organisation for Economic Co-operation and Development (OECD). RESULTS: The time
      and regional trends in LE provided by our estimates are closely similar to those
      published by the UN at the country level. According to UN data, LE (men plus
      women) varied from 70 years in Estonia to almost 79 years in Sweden in the period
      1995-1999. LE increased markedly over the 20-year study period in most countries
      except Estonia and Denmark. LE correlated directly with GDP, national expenditure
      on health and relative survival for all cancers combined. We found that within
      country LE variation was large in some countries (particularly the UK). Sweden,
      Iceland, Switzerland, and parts of Spain and Italy had high LE; eastern European
      countries had low LE. CONCLUSIONS: Detailed area-specific life tables are
      essential for reliable estimation of relative cancer survival and its comparison
      across populations, since LE varies markedly across Europe. Where not available,
      life tables can be constructed to the required level of detail using mathematical
      approaches.

PMID- 14684500
TI  - European health systems and cancer care.
AB  - INTRODUCTION: Data on the survival of all incident cases collected by population
      based cancer registries make it possible to evaluate the overall performance of
      diagnostic and therapeutic actions on cancer in those populations. EUROCARE-3 is
      the third round of the EUROCARE project, the largest cancer registry population
      based collaborative study on survival in European cancer patients. The EUROCARE-3
      study analysed the survival of cancer patients diagnosed from 1990 to 1994 and
      followed-up to 1999. Sixty-seven cancer registries of 22 European countries
      characterised by differing health systems participated in the study. This paper
      includes essays providing brief overviews of the state and evolution of the
      health systems of the considered countries and comments on the relation between
      cancer survival in Europe and some European macro-economic and health system
      indicators, in the 1990s. OVERVIEW OF THE EUROPEAN HEALTH SYSTEMS: The European
      health systems underwent a great deal of reorganisation in the last decade; a
      general tendency being to facilitate expanding involvement of the private sector
      in health care, a process which occurred mainly in the eastern countries (i.e.
      the Czech Republic, Estonia, Poland, Slovakia and Slovenia). In contrast,
      organisational changes in the northern European countries (i.e. Denmark, Iceland,
      Finland and Sweden) tended to confirm the established public sector systems.
      Other countries, including the UK and some southern European countries (i.e.
      England, Scotland, Wales, Malta and Italy) have reduced the public role while the
      systems remain basically public, at least at present. Our findings clearly
      suggest that cancer survival (all cancer combined) is related to macro-economic
      variables such as the gross domestic product (GDP), the total national (public
      and private) expenditure on health (TNEH) and the total public expenditure on
      health (TPEH). We found, however, that survival is related to wealth (GDP), but
      only up to a certain level, after which survival continues to be related to the
      level of health investment (both TNEH and TPEH). According to the Organisation
      for Economic Co-operation and Development (OECD), the TNEH increased during the
      1990s in all EUROCARE-3 countries, while the ratio of TPEH to TNEH reduced in all
      countries except Portugal. CONCLUSIONS: Cancer survival depends on the widespread
      application of effective diagnosis and treatment modalities, but our enquiry
      suggests that the availability of these depends on macro-economic determinants,
      including health and public health investment. Analysis of the relationship
      between health system organisation and cancer outcome is complicated and requires
      more information than is at present available. To describe cancer and cancer
      management in Europe, the European Cancer Health Indicator Project (EUROCHIP) has
      proposed a list of indicators that have to be adopted to evaluate the effects on
      outcome of proposed health system modifications.

PMID- 14684501
TI  - EUROCARE-3: survival of cancer patients diagnosed 1990-94--results and
      commentary.
AB  - EUROCARE-3 analysed the survival of 1815584 adult cancer patients diagnosed from
      1990 to 1994 in 22 European countries. The results are reported in tables, one
      per cancer site, coded according to the International Classification of Diseases
      (ICD)-9 classification. The main findings of the tables are summarised and
      commented on in this article. For most solid cancers, wide differences in
      survival between different European populations were found, as also reported by
      EUROCARE-1 and EUROCARE-2, despite a remarkable (10%) overall increase in cancer
      survival from 1985 to 1994. Survival was highest in northern Europe (Sweden,
      Norway, Finland and Iceland), and fairly good in central-southern Europe (France,
      Switzerland, Austria and Spain). Survival was particularly low in eastern Europe,
      low in Denmark and the UK, and fairly low in Portugal and Malta. The mix of
      tumour stage at diagnosis explains much of the survival differences for cancers
      of the digestive tract, female reproductive system, breast, thyroid, and also
      skin melanoma. For tumours of the urinary tract and prostate, the differences
      were explained mainly by differences in diagnostic criteria and procedures. The
      case mix by anatomic subsite largely explains differences in survival for head
      and neck cancers. For oesophagus, pancreas, liver and brain cancer, with poor
      prognoses, survival differences were limited. Tumours, for which highly effective
      treatments are available, such as testicular cancer, Hodgkin's lymphoma and some
      haematological malignancies, had fairly uniform survival across Europe. Survival
      for all tumours combined (an indicator of the overall cancer care performance of
      a nation's health system) was better in young than old patients, and better in
      women than men. The affluence of countries influenced overall cancer survival
      through the availability of adequate diagnostic and treatment procedures, and
      screening programmes.

PMID- 14684502
TI  - Childhood cancer survival in Europe.
AB  - BACKGROUND: EUROCARE-3 collected data from 45 population-based cancer registries
      in 20 countries on 24 620 European children aged from 0 to 14 years diagnosed
      with malignancy in the period 1990-1994. METHODS: Five-year survival between
      countries was compared for all malignancies and for the major diagnostic
      categories, adjusting for age, and estimated average European survival weighting
      for differences in childhood populations. RESULTS: For all cancers combined,
      survival variation was large (45% in Estonia to 90% in Iceland), and was
      generally low (60-70%) in eastern Europe and high (> or =75%) in Switzerland,
      Germany and the Nordic countries (except Denmark). The Nordic countries had the
      highest survival for four of the seven major tumour types: nephroblastoma (92%),
      acute lymphoid leukaemia (85%), CNS tumours (73%) and acute non-lymphocytic
      leukaemia (62%). The eastern countries had lowest survival: 89% for Hodgkin's
      disease, 71% for nephroblastoma, 68% for acute lymphoid leukaemia, 61% for non
      Hodgkin's lymphoma, 57% for central nervous system (CNS) tumours and 29% for
      acute non-lymphocytic leukaemia. CONCLUSIONS: The Nordic countries represent a
      survival gold standard to which other countries can aspire. Since most childhood
      cancers respond well to treatment, survival differences are attributable to
      differences in access (including referral and timely diagnosis) and use of modern
      treatments; however, the obstacles to access and application of standard
      treatments probably vary markedly with country.

PMID- 14684503
TI  - EUROCARE-3 summary: cancer survival in Europe at the end of the 20th century.

PMID- 14684504
TI  - Electronic availability of EUROCARE-3 data: a tool for further analysis.
AB  - The EUROCARE-3 CD-ROM has been developed to provide more detailed data with
      respect to those published in the monograph. The CD-ROM provides estimates of age
      specific and age-standardised survival figures, cumulative and interval-specific
      survival, observed and relative survival for 47 cancer sites or combinations of
      sites, based on >4 million adult cancer patients diagnosed from 1983 to 1994 and
      reported from 56 European cancer registries. In addition, the CD-ROM provides
      observed survival proportions for 25 childhood cancer entities based on 23,000
      young patients diagnosed from 1990 to 1994. Survival indicators, corresponding
      standard errors and confidence intervals can be selected according to cancer
      site, registry or country, sex, age class and disease duration. Basic graphical
      display and export facilities have also been provided. As an example of how to
      use this CD-ROM, this paper will report a descriptive analysis of relative
      survival patterns for all cancers combined, by age, sex and country. The EUROCARE
      3 CD-ROM can be ordered free of charge or directly downloaded at
      http://www.eurocare.it.

PMID- 14684505
TI  - Lee Rogers, AJR Editor in Chief, 1995-2003: a golden age for the yellow journal.

PMID- 14684506
TI  - Alzheimer's disease: neuropathologic findings and recent advances in imaging.

PMID- 14684507
TI  - Imaging manifestations of abdominal sarcoidosis.

PMID- 14684508
TI  - The relationship of managed care to business, professional, and organizational
      aspects of radiology practices.
AB  - OBJECTIVE: We sought to determine the extent of managed care involvement among
      radiology practices of different types, locations, and sizes; the factors
      associated with differences in involvement; and the impact of managed care on
      professional, organizational, financial, and hospital-relations aspects of
      radiology practices. MATERIALS AND METHODS: A survey was mailed in 1999 to a
      sample of 970 radiology practices; completed, usable surveys were returned by 66%
      of the practices. Three indicators of managed care were used: a practice's
      percentage of managed care (HMOs plus preferred provider organizations), local
      area HMO penetration rate, and self-reported perceived effect of managed care.
      RESULTS: Percentage of managed care averaged 30% but was 40% for multispecialty
      groups. It was relatively high in large metropolitan areas, for practices with no
      hospital activity, and for practices with any owners who were not practice
      members. The three measures of managed care were only moderately correlated
      (correlation coefficient, 0.25-0.33). None of the managed care variables had a
      statistically significant effect on days provided for vacation and continuing
      medical education, promptness of payment, years required for practice ownership
      (partnership), and percentage of practice members who were owners. Higher
      percentage of managed care was associated with higher collection rates, whereas
      greater perceived impact of managed care had the opposite association. Two thirds
      of practices belonged to at least one managed care-related organization such as
      an independent practice association. Most radiology practices reported no
      involvement in the managed care negotiations of hospitals, which was true even
      when the hospital's negotiations included the radiologists' fees or when the
      practice determined its level of involvement. CONCLUSION: Many negative outcomes
      most feared by radiologists regarding the effect of managed care have not
      materialized. Perceptions of practices as to the effect of managed care seem to
      reflect negative aspects of their general situation, not only realities of
      managed care.

PMID- 14684509
TI  - High-resolution CT findings of severe acute respiratory syndrome at presentation
      and after admission.
AB  - OBJECTIVE: The aim of this study was to assess the high-resolution CT (HRCT)
      findings at presentation and after hospital admission in patients with severe
      acute respiratory syndrome (SARS). MATERIALS AND METHODS: We reviewed the HRCT
      findings at presentation (n = 12) and after hospital admission (n = 25) of 29
      patients with SARS and compared the HRCT findings with the radiographic findings.
      HRCT scans were obtained using 1-mm (n = 28) or 2-mm (n = 1) collimation. The
      radiographs and HRCT scans were reviewed independently by two observers who
      reached a decision by consensus. RESULTS: All patients had abnormal findings on
      HRCT at presentation. Eight of these 12 patients had normal findings on
      radiographs. The predominant HRCT findings at presentation consisted of
      unilateral (n = 6) or bilateral (n = 2) ground-glass opacities or focal
      unilateral (n = 2) or bilateral (n = 2) areas of consolidation. All patients
      showed progression of disease on follow-up. The predominant HRCT findings on
      follow-up CT scans consisted of unilateral (n = 2) or bilateral ground-glass
      opacities (n = 13), unilateral (n = 2) or bilateral consolidation (n = 5), or a
      mixed bilateral pattern of ground-glass attenuation, consolidation, and
      reticulation (n = 3). Reticulation with associated architectural distortion and
      mild traction bronchiectasis was present in eight patients. CONCLUSION: HRCT can
      show parenchymal abnormalities in patients with SARS who have normal findings on
      radiographs at presentation. Follow-up CT scans obtained in hospitalized patients
      show findings consistent with fibrosis in a small percentage of patients.

PMID- 14684510
TI  - Chest radiographic manifestations of severe acute respiratory syndrome in health
      care workers: the Toronto experience.
AB  - OBJECTIVE: The purpose of this article is to describe the chest radiographic
      manifestations of severe acute respiratory syndrome (SARS) in previously
      uninfected health care workers during the early stages of an outbreak in Toronto,
      Canada. CONCLUSION: The study group was composed of 13 patients from a single
      institution. Three distinct chest radiographic patterns were observed: focal
      peripheral air-space disease at presentation with gradual resolution (most common
      pattern, 10/13 patients), normal findings on chest radiography at presentation
      followed by focal air-space disease (2/13 patients), and normal findings on chest
      radiography at presentation followed by a "round" pneumonia pattern (1/13
      patients). There was no evidence of pleural reaction, lymphadenopathy, or
      interstitial changes.

PMID- 14684511
TI  - High-resolution CT findings in patients with severe acute respiratory syndrome: a
      pattern-based approach.
AB  - OBJECTIVE: We retrospectively reviewed high-resolution CT (HRCT) examinations of
      the lungs performed in 27 confirmed cases of severe acute respiratory syndrome
      (SARS). The HRCT findings at different phases of the illness were analyzed.
      CONCLUSION: A defined pattern of HRCT findings is observed in different phases of
      SARS, which is characterized by focal ground-glass and crazy paving patterns in a
      scattered distribution at presentation, followed by development of interstitial
      thickening, consolidation, pleural reaction, and scarring. Spontaneous
      pneumomediastinum is a distinct complication during the course of the illness.

PMID- 14684512
TI  - Providing optimal radiology service in the severe acute respiratory syndrome
      outbreak: use of mobile CT.
AB  - OBJECTIVE: Severe acute respiratory syndrome (SARS) is a serious atypical
      pneumonia caused by a novel pathogen. We describe our experience using a mobile
      CT scanner in an improvised isolation ward with life-support systems, portable
      lead shielding, and strict barrier nursing. This scanner was used exclusively for
      patients with SARS and patients with other illnesses who were also thought to
      have SARS. This arrangement freed the other CT scanners in the main department
      for non-SARS patients. In 5 weeks, 90 studies were performed; no cases of cross
      infection of health care workers were reported. CONCLUSION: Mobile CT may be used
      to provide dedicated radiology services to seriously ill patients requiring
      strict isolation during an infectious disease outbreak.

PMID- 14684513
TI  - Comparison of interpretations of CT angiograms in the evaluation of suspected
      pulmonary embolism by on-call radiology fellows and subsequently by radiology
      faculty.
AB  - OBJECTIVE: Our objective was to evaluate interobserver variability in
      interpretations performed by on-call radiology fellows and subsequently by
      attending radiologists of CT angiograms obtained for clinically suspected
      pulmonary embolism and to evaluate factors contributing to discrepancies.
      MATERIALS AND METHODS: Written interpretations made by on-call fellows were
      compared with reports approved by attending radiologists for all CT angiograms
      obtained for suspected pulmonary embolism after work hours and on weekends in a
      recent 19-month period. Interpretations were stratified as positive, negative, or
      equivocal for pulmonary embolism. In cases of discordant interpretations, those
      CT angiograms were rereviewed by two thoracic radiologists; then patient medical
      records were reviewed for evidence of clinical effect. Technical and patient
      related reasons for discordant interpretations of CT angiograms were recorded.
      RESULTS: Six hundred fifty-eight oncology patients were examined on CT
      angiography; five were examined twice. The fellows reported 137 CT angiograms
      (21%) as positive, 498 (75%) as negative, and 28 (4%) as equivocal for pulmonary
      embolism. Interpretations of the fellows and attending radiologists agreed in 93%
      (615/663) of CT angiograms (kappa = 0.80). The concordance rates for CT
      angiograms interpreted by fellows as positive (89%, 122/137), negative (96%,
      479/498), and equivocal (50%, 14/28) were significantly different from each other
      (p < 0.001 for each). A significantly greater proportion of CT angiograms with
      discordant interpretations was reported to be technically limited (p < 0.01). No
      clear adverse clinical events were attributed to discordant interpretations of CT
      angiograms, although the death of one patient in that subgroup was of
      indeterminate cause. CONCLUSION: In the evaluation of CT angiograms obtained for
      suspected pulmonary embolism, on-call fellows showed good agreement with
      attending radiologists. CT angiograms with discordant interpretations often were
      limited by technical or patient-related factors.

PMID- 14684514
TI  - Bronchial artery dilatation on MDCT scans of patients with acute pulmonary
      embolism: comparison with chronic or recurrent pulmonary embolism.
AB  - OBJECTIVE: The purpose of our study was to compare the bronchial arteries of
      patients with acute pulmonary embolism with those of patients with chronic or
      recurrent pulmonary embolism. MATERIALS AND METHODS: Twenty-seven patients with
      acute pulmonary embolism and 14 patients with chronic or recurrent pulmonary
      embolism were retrospectively identified from 700 consecutive patients with
      suspected pulmonary embolism. The case data for the patients were assessed by two
      thoracic radiologists whose final judgments were reached by consensus. On the
      MDCT pulmonary angiograms obtained in these patients, the bronchial arteries were
      assessed by finding enhancing, small, round or curvilinear structures within the
      mediastinum and tracing their paths along the bilateral main bronchi. Bronchial
      arteries with a diameter greater than 1.5 mm were considered to be dilated.
      RESULTS: The diameters of the bronchial arteries in the group with chronic or
      recurrent pulmonary embolism were significantly larger than diameters of the
      bronchial arteries in the group with acute pulmonary embolism (p = 0.0002).
      Dilatation of bronchial arteries was observed in two of the 27 patients with
      acute pulmonary embolism and in seven of 14 patients with chronic or recurrent
      pulmonary embolism. This difference was statistically significant (p = 0.004). No
      dilated bronchial arteries were seen in patients who had acute pulmonary embolism
      but had no a history of deep venous thrombosis. CONCLUSION: Acute pulmonary
      embolism did not appear to cause dilatation of bronchial arteries, whereas
      chronic or recurrent pulmonary embolism was frequently associated with dilated
      bronchial arteries. In patients in whom the distinction between acute and chronic
      or recurrent pulmonary embolism on MDCT pulmonary angiography is clinically
      unclear and in whom the bronchial arteries are dilated, a diagnosis of chronic or
      recurrent pulmonary embolism should be favored.

PMID- 14684516
TI  - Squamous cell carcinoma coexisting in rounded atelectasis: diagnostic pitfalls.

PMID- 14684515
TI  - Dynamic perfusion MRI versus perfusion scintigraphy: prediction of postoperative
      lung function in patients with lung cancer.
AB  - OBJECTIVE: The purpose of this study was to determine the capability of dynamic
      perfusion MRI as an alternative to pulmonary perfusion scintigraphy for
      prediction of postoperative lung function in patients with lung cancer. SUBJECTS
      AND METHODS. Sixty patients with lung cancer (35 men, 25 women) underwent dynamic
      perfusion MRI, perfusion scintigraphy, and preoperative and postoperative
      pulmonary function tests (forced expiratory volume in 1 sec [FEV(1)]). Perfusion
      MRIs were obtained with a 3D turbo field-echo sequence (TR/TE, 2.7/0.6; flip
      angle, 40 degrees; matrix, 128 x 96) using a 1.5-T scanner. Regional blood flow
      was calculated from the signal intensity-time curves after bolus injection of
      contrast medium on MRI (Q(MRI)) and uptake ratios of radioisotope on perfusion
      scintigraphy (Q(PS)). Postoperative lung functions predicted by MRI (FEV(1,MRI))
      and perfusion scintigraphy (FEV(1,PS)) were calculated from preoperative FEV(1)
      and regional Qs. To determine the capability of MRI as an alternative to
      scintigraphy, we evaluated correlations and the limits of agreement between
      predicted FEV(1,MRI) and postoperative FEV(1) and between predicted FEV(1,PS) and
      postoperative FEV(1). RESULTS: The correlation coefficient of postoperative
      FEV(1) with FEV(1,MRI) (r = 0.93, p < 0.0001) was better than that with FEV(1,PS)
      (r = 0.89, p < 0.0001). The limits of agreement between postoperative FEV(1) and
      predicted FEV(1,MRI) (0.9% +/- 10.4%) were smaller than those between
      postoperative FEV(1) and predicted FEV(1,PS) (2.1% +/- 13.2%). CONCLUSION:
      Dynamic perfusion MRI is a feasible alternative to pulmonary perfusion
      scintigraphy for predicting postoperative lung function in patients with lung
      cancer.

PMID- 14684517
TI  - Frequency and severity of air trapping at dynamic expiratory CT in patients with
      tracheobronchomalacia.
AB  - OBJECTIVE: The purpose of this study was to compare the frequency and severity of
      air trapping in patients with and without tracheobronchomalacia using dynamic
      expiratory volumetric CT. MATERIALS AND METHODS: The study group consisted of 20
      subjects, including 10 patients with bronchoscopically proven
      tracheobronchomalacia and 10 control subjects of similar ages without
      tracheobronchomalacia. All 20 subjects underwent MDCT performed at the end of
      deep inspiration and during dynamic expiration. The images were analyzed at three
      lung levels, and the extent of air trapping was assessed visually using a 5-point
      scale. For each subject, a total air-trapping score was derived by summing the
      values for the three lung levels (possible range, 0-12). Statistical analysis was
      performed using the Mann-Whitney U test. RESULTS: In the tracheobronchomalacia
      group, 10 (100%) of 10 patients showed air trapping, with a median score of 5
      (range, 2-12). In the control group, six (60%) of 10 subjects showed air
      trapping, with a median score of 2 (range, 0-3). The median total air-trapping
      score was significantly higher (p < 0.001) for the tracheobronchomalacia group
      compared with the control group. Excessive central airway collapse (expiratory
      reduction in cross-sectional area of > 50%) was seen on CT scans in all
      tracheobronchomalacia patients but in none of the control subjects. CONCLUSION:
      Air trapping was observed with a higher frequency and greater severity in
      patients with tracheobronchomalacia than in a control group of patients of
      similar ages without tracheobronchomalacia.

PMID- 14684518
TI  - CT findings of surgically resected large cell neuroendocrine carcinoma of the
      lung in 38 patients.
AB  - OBJECTIVE: We sought to assess the CT features of surgically resected large cell
      neuroendocrine carcinoma of the lung. MATERIALS AND METHODS: The cases of all
      patients who underwent surgical resection for primary lung cancer in a single
      institution from 1993 to 2000 and who received an initial diagnosis of poorly
      differentiated non-small cell lung carcinoma, small cell carcinoma, carcinoid
      tumor, and large cell neuroendocrine carcinoma were histologically reviewed. The
      findings for 43 patients were histologically reclassified and confirmed as large
      cell neuroendocrine carcinoma. The CT scans available for 38 patients were
      evaluated by two observers. RESULTS: In the 38 patients, six central tumors and
      32 peripheral tumors, with diameters ranging from 12 to 92 mm (mean +/- SD, 32 +/
      19 mm), were identified. None of the tumors had air bronchograms or
      calcification in the mass or nodule. Of the 19 patients with thin-section CT
      scans, 14 (74%) showed the tumor-lung interface as well defined and five (26%)
      showed the interface to be ill defined. Lobulation was identified on 15 scans
      (79%) and spiculation was evident on six scans (32%). On contrast-enhanced CT
      scans, inhomogeneously enhanced tumors appeared to be larger (51 +/- 18 mm) than
      homogeneously enhanced tumors (25 +/- 10 mm; p < 0.001). At histopathologic
      examination, gross necrosis was noted in 20 of 28 patients who had undergone
      contrast-enhanced CT, and the cause of inhomogeneous enhancement on CT scans was
      determined to be intratumoral necrosis. Multiple microscopic necroses were
      present in all 28 patients. CONCLUSION: Large cell neuroendocrine carcinoma
      usually appears as a well-defined and lobulated tumor with no air bronchograms or
      calcification. The inhomogeneous enhancement (caused by necrosis) seen in large
      cell neuroendocrine carcinomas with large diameters is not necessarily apparent
      in small-diameter (< 33 mm) large cell neuroendocrine carcinomas, even if the
      tumor contains necrosis.

PMID- 14684519
TI  - CT with histopathologic correlation of FDG uptake in a patient with pulmonary
      granuloma and pleural plaque caused by remote talc pleurodesis.

PMID- 14684520
TI  - Ischemic cardiomyopathy: value of different MRI techniques for prediction of
      functional recovery after revascularization.
AB  - OBJECTIVE: The purpose of this study was to compare the value of different MRI
      techniques for the assessment of myocardial viability. SUBJECTS AND METHODS.
      Eighteen infarct patients (mean age +/- SD, 62 +/- 8 years) with myocardial
      ischemia were examined using MRI before and after revascularization. The MRI
      study before treatment consisted of an evaluation of first-pass perfusion,
      contractile function at rest and during dobutamine stress, and delayed
      hyperenhancement. Findings were correlated with segmental and global cardiac
      function after revascularization. RESULTS: In initially dysfunctional segments,
      the likelihood of functional recovery after revascularization was 91% for
      segments without delayed hyperenhancement, 43% for segments with delayed
      hyperenhancement with transmural extent of 75% or less, and 8% for segments with
      delayed hyperenhancement with transmural extent of more than 75% (p < 0.05).
      Improved function at dobutamine stress MRI indicated functional recovery in 87%,
      whereas functional recovery was observed in only 30% of segments not responding
      at dobutamine stress MRI (p < 0.05). No significant correlation was found between
      the results of first-pass perfusion MRI and functional recovery. The ejection
      fraction after revascularization was best predicted by the MRI-derived infarct
      volume (p < 0.001, R(2) = 0.63). CONCLUSION: A simple protocol consisting of
      baseline contractility and delayed enhancement MRI studies is adequate to
      differentiate dysfunctional but viable from nonviable myocardium. Dobutamine
      stress and perfusion MRI studies offer little or no additional information.

PMID- 14684521
TI  - Sonographic, mammographic, and histopathologic correlation of symptomatic ductal
      carcinoma in situ.
AB  - OBJECTIVE: The purpose of this study was to describe the features of symptomatic
      ductal carcinoma in situ (DCIS) of the breast shown on high-resolution sonography
      and to correlate them with findings from mammography and histopathology to
      evaluate the prognostic ability of sonographic findings. MATERIALS AND METHODS:
      We retrospectively reviewed mammographic and sonographic images of 60 DCIS
      lesions from 55 symptomatic women. Images were reviewed by a radiologist who knew
      that the patients had DCIS but had no other information regarding pathology.
      Lesions were evaluated pathologically and classified using the Van Nuys
      classification system. Statistical comparisons were made using Fisher's exact
      test. RESULTS: Of the 60 lesions, 33 were classified as Van Nuys group 1, 19 as
      Van Nuys group 2, and eight as Van Nuys group 3. Six (10%) of the 60 lesions were
      not visible on sonography, and 12 lesions (20%) were not visible on mammography.
      Sonography revealed a mass in 43 cases (72%), ductal changes in 14 cases (23%),
      and architectural distortion in four cases (7%). Eight lesions had more than one
      of these features. A sonographically visualized, irregularly shaped mass with
      indistinct or angular margins and no posterior acoustic shadowing or enhancement
      was associated with a high Van Nuys classification (p < 0.05).
      Microcalcifications were visible on sonography in 13 (22%) of the 60 lesions or
      on mammography in 25 lesions (42%). Both findings were associated with a high Van
      Nuys classification (p < 0.05). CONCLUSION: Although sonography can reveal
      microcalcifications within masses, it is unreliable in depicting and
      characterizing the morphology and extent of microcalcifications, particularly
      when they are in isolation. Therefore, sonography should not be used to replace
      mammography but instead as an adjunctive tool to increase the sensitivity of
      mammography in breast diagnosis.

PMID- 14684522
TI  - Acute injury of the articular cartilage and subchondral bone: a common but
      unrecognized lesion in the immature knee.
AB  - OBJECTIVE: We studied the prevalence of injuries of the articular cartilage and
      subchondral bone after acute trauma in skeletally immature knees using high
      resolution MRI. MATERIALS AND METHODS: We reviewed knee MRIs of 126 young
      children and adolescents suspected to have internal knee derangement, including
      82 with open physes and a control group of 44 who were skeletally mature. High
      resolution proton density and T2-weighted pulse sequences were used in all
      patients. The prevalence of common injuries in the two groups was compared using
      chi-square analysis. Levels of interobserver agreement for evaluation of chondral
      lesions in the skeletally immature group were determined using the kappa
      statistic. RESULTS: In the skeletally immature group, chondral lesions were the
      most prevalent injuries (prevalence = 0.34, p = 0.009) followed by meniscal and
      anterior cruciate ligament injuries (prevalence = 0.23 and 0.24, respectively).
      No significant difference in the prevalence of chondral injury before and after
      physeal closure was seen (p = 0.45). There was no significant difference in the
      prevalence of anterior cruciate ligament injuries between the two groups, but
      meniscal injuries were more prevalent in the skeletally mature patients
      (prevalence = 0.41, p = 0.037). Interobserver agreement for chondral injuries in
      the group with open physes was good (weighted kappa = 0.45-0.51). CONCLUSION: The
      most common injuries occurring as a result of acute trauma to the immature knee
      were chondral. In patients with open physes, chondral injuries were significantly
      more prevalent than anterior cruciate ligament and meniscal injuries.

PMID- 14684523
TI  - MRI findings of septic arthritis and associated osteomyelitis in adults.
AB  - OBJECTIVE: The purpose of this study was to describe the soft-tissue, synovial,
      and osseous MRI findings of septic arthritis. MATERIALS AND METHODS: At 1.5 T (T1
      weighted, T2-weighted or STIR, and contrast-enhanced images), 50 consecutive
      cases of septic arthritis were evaluated by two observers for synovial
      enhancement, perisynovial edema, joint effusion, fluid outpouching, fluid
      enhancement, and synovial thickening. The marrow was assessed for abnormal signal
      on T1- and T2-weighted images or after contrast enhancement. We noted whether the
      marrow signal was diffuse or abnormal in bare areas. MRI findings were compared
      with microbiologic, clinical, and surgical data and diagnoses. RESULTS: The
      frequency of MRI findings in septic joints was as follows: synovial enhancement
      (98%), perisynovial edema (84%), joint effusions (70%), fluid outpouching (53%),
      fluid enhancement (30%), and synovial thickening (22%). The marrow showed bare
      area changes (86%), abnormal T2 signal (84%), abnormal gadolinium enhancement
      (81%), and abnormal T1 signal (66%). Associated osteomyelitis more often showed
      T1 signal abnormalities and was diffuse. CONCLUSION: Synovial enhancement,
      perisynovial edema, and joint effusion had the highest correlation with the
      clinical diagnosis of a septic joint. However, almost a third of patients with
      septic arthritis lacked an effusion. Abnormal marrow signal-particularly if it
      was diffuse and seen on T1-weighted images-had the highest association with
      concomitant osteomyelitis.

PMID- 14684524
TI  - Sonography of peripheral nerve pathology.

PMID- 14684525
TI  - Calcaneal chondroblastoma with secondary aneurysmal bone cyst.

PMID- 14684526
TI  - MRI findings associated with distal tibiofibular syndesmosis injury.
AB  - OBJECTIVE: Our objective was to describe the MRI findings associated with acute
      and chronic distal tibiofibular syndesmosis injury. MATERIALS AND METHODS: Ninety
      four 1.5-T MRIs of ankles of 90 individuals with histories of severe sprain were
      assessed by two musculoskeletal radiologists for syndesmosis injury (acute, edema
      of the syndesmosis; chronic, disruption or thickening of the syndesmosis without
      edema). We examined associated MRI findings, including anterior talofibular
      ligament injury (scar, chronic injury; edema, acute injury), bone bruise,
      osteochondral lesion, tibiofibular joint congruity, tibiofibular recess height,
      and osteoarthritis. The Fisher's exact test and analysis of variance test were
      used to evaluate the significance of the associations. RESULTS: In 94 ankles,
      syndesmosis injury was seen in 63% (n = 59; 23 acute; 36 chronic). Anterior
      talofibular ligament injury (acute or chronic) was seen on MRIs in 74% (n = 70;
      49 with syndesmosis injury; 21 without; p = 0.03). Bone bruises were present in
      24% (n = 23; 18/23 acute; 4/36 chronic; 4/35 no injury; p < 0.0001). Of these,
      talar dome osteochondral lesions were present in 28% (n = 26; 11/23 acute; 14/36
      chronic; 1/35 no injury; p = 0.0001; 13 medial; 13 lateral). The tibiofibular
      joint was incongruent in 33% (n = 31; 6/23 acute; 21/36 chronic; 4/35 no injury;
      p < 0.0001). The tibiofibular recess (mean +/- SD) was 1.2 +/- 0.92 cm in acute
      cases, 1.4 +/- 0.57 cm in chronic cases, and 0.54 +/- 0.68 cm in cases with no
      syndesmosis injury (p < 0.0001). Osteoarthritis was present in 10% (n = 9; 1/23
      acute; 7/36 chronic; 1/35 no injury; p = 0.06). CONCLUSION: Injury to the distal
      tibiofibular syndesmosis has a significant association with a number of secondary
      findings on MRI, including anterior talofibular ligament injury, bone bruises,
      osteochondral lesions, tibiofibular joint congruity, and height of the
      tibiofibular recess.

PMID- 14684527
TI  - MRI diagnosis of tears of the hip abductor tendons (gluteus medius and gluteus
      minimus).
AB  - OBJECTIVE: The purpose of our study was to determine the accuracy of MRI for
      diagnosing tears of the hip abductor tendons (gluteus medius and gluteus minimus)
      and to evaluate various signs of tendon disruption. MATERIALS AND METHODS: We
      retrospectively evaluated MRIs of 74 hips (in 45 patients) that were obtained
      using 35- to 42-cm fields of view and interpreted using primary and secondary
      signs of tendon disruption. Fifteen hips had surgically proven abductor tendon
      tears, and 59 hips were either asymptomatic or had surgically confirmed intact
      tendons. MRI findings were scored by two radiologists through consensus and then
      again independently by a third radiologist to determine interobserver agreement.
      RESULTS: The accuracy of MRI for the diagnosis of tears of the abductor tendons
      was 91%. Statistically significant associations were found between tears of the
      abductor tendons and areas of high signal intensity superior to the greater
      trochanter on T2-weighted images (p < 0.0001), tendon elongation in the gluteus
      medius (p = 0.0028), tendon discontinuity (p = 0.016), and areas of high signal
      intensity lateral to the greater trochanter on T2-weighted images (p = 0.0213).
      Interobserver agreement was good to fair. CONCLUSION: MRI showed good accuracy
      for the diagnosis of tears of the gluteus medius and gluteus minimus tendons. The
      identification of an area of T2 hyperintensity superior to the greater trochanter
      had the highest sensitivity and specificity for tears at 73% and 95%,
      respectively.

PMID- 14684528
TI  - MRI diagnosis of subpubic cartilaginous cyst.

PMID- 14684529
TI  - Anatomy of and abnormalities associated with Kager's fat Pad.

PMID- 14684530
TI  - Panoramic versus conventional radiography of scaphoid fractures.
AB  - OBJECTIVE: The objective of this study was to compare the diagnostic value of
      panoramic and conventional radiography in the detection of fractures of the
      carpal scaphoid bone. MATERIALS AND METHODS: Panoramic (orthopantomographic) and
      conventional radiographs of 90 patients with acute or chronic wrist trauma were
      reviewed retrospectively. Images were analyzed and reviewed independently by four
      observers: two radiologists and two traumatologists. The kappa statistic was used
      to calculate intraand interobserver agreement and the correlation between the two
      imaging techniques. RESULTS: Panoramic radiography of the wrist was superior to
      conventional radiography in ruling out scaphoid fractures (74%, 20/27) in
      patients with suspicious findings on conventional radiography; revealed more
      cases of scaphoid fractures (21.4%, 12/56); and revealed more cases of delayed
      union (n = 2), nonunion (n = 3), and union (n = 3). Agreement values were higher,
      with better inter- and intraobserver agreement, for the panoramic examinations
      than for the conventional radiographic examinations. CONCLUSION: The panoramic
      examination of the wrist is a useful technique for the diagnosis and follow-up of
      scaphoid fractures. Its use is recommended as a complement to conventional
      radiography in cases with inconclusive findings.

PMID- 14684532
TI  - MDCT of tendon abnormalities using volume-rendered images.
AB  - OBJECTIVE: Our objectives were to report tendon abnormalities diagnosed on 3D
      volume-rendered images from MDCT data and to validate the clinical usefulness of
      this technique. CONCLUSION: We present 18 tendon abnormalities from 16 patients
      that were diagnosed on 3D volume-rendered MDCT images generated by commercially
      available software. Certain abnormalities such as avulsions, partial tears, and
      dislocations of tendons are clearly shown by this technique. This technique may
      prove useful in the evaluation of tendon abnormalities when MRI or sonography
      cannot be used.

PMID- 14684534
TI  - Glycosaminoglycan distribution in cartilage as determined by delayed gadolinium
      enhanced MRI of cartilage (dGEMRIC): potential clinical applications.
AB  - OBJECTIVE: We sought to describe a range of in vivo observations of
      glycosaminoglycan distribution in knee cartilage using the delayed gadolinium
      enhanced MRI of cartilage technique. CONCLUSION: The index of glycosaminoglycan
      distribution, T1(Gd), can exceed 500 msec (denoting high glycosaminoglycan) or
      can be less than 300 msec, with focal areas as low as 240 msec. Compartmental
      differences, as well as focal defects within the knee, were observed in patients
      who had sustained injuries to the ligaments and menisci of the knee or who had
      chronic osteoarthritis. Overall, these results suggest the need for further
      research into the biochemical changes seen during disease progression and the
      effects of therapeutic interventions.

PMID- 14684535
TI  - Helical CT of Rib Lesions: A Pattern-Based Approach.

PMID- 14684536
TI  - Optimized assessment of hand vascularization on contrast-enhanced MR angiography
      with a subsystolic continuous compression technique.

PMID- 14684537
TI  - Intracranial dural arteriovenous fistulas: evaluation with combined 3D time-of
      flight MR angiography and MR digital subtraction angiography.
AB  - OBJECTIVE: The purpose of this study was to compare the diagnostic utility of 3D
      time-of-flight (TOF) MR angiography and MR digital subtraction angiography in
      patients with angiographically proven moderate- to high-flow intracranial dural
      arteriovenous fistula. MATERIALS AND METHODS: Two neuroradiologists, unaware of
      patients' histories and angiographic findings, retrospectively reviewed 17 MR
      angiograms with 3D TOF MR angiography and MR digital subtraction angiography in
      15 patients with dural arteriovenous fistula and also reviewed 35 MR angiograms
      in control patients without findings of dural arteriovenous fistula on
      angiography. Disagreements were resolved by consensus. RESULTS: In patients with
      dural arteriovenous fistula, source images of 3D TOF MR angiography showed two
      abnormal findings: multiple high-intensity curvilinear or nodular structures
      adjacent to the sinus wall and high-intensity areas in the venous sinus. Findings
      of multiple high-intensity structures adjacent to the sinus wall were observed in
      all cases of dural arteriovenous fistula. Findings of high-intensity areas in the
      venous sinus were observed in 13 of 17 cases of dural arteriovenous fistula.
      Findings of multiple high-intensity structures adjacent to the sinus wall were
      not observed in any control subjects. Findings of high-intensity areas within the
      venous sinus were observed in five of 35 control subjects. Findings of MR digital
      subtraction angiography showed early filling of the venous sinus, suggestive of
      dural arteriovenous fistula, in 13 of 15 patients with dural arteriovenous
      fistula. Sensitivity and specificity of multiple high-intensity structures
      adjacent to the sinus wall, high-intensity areas in the venous sinus, and early
      filling of the venous sinus were 100% and 100%, 76% and 86%, and 87% and 100%,
      respectively. Although 3D TOF MR angiography failed to show the findings of
      retrograde cortical venous drainage and venous sinus occlusion, MR digital
      subtraction angiography clearly showed both findings in all five subjects.
      CONCLUSION: A protocol including both 3D TOF MR angiography (source images) and
      MR digital subtraction angiography allowed the diagnosis of moderate- to high
      flow dural arteriovenous fistula. In addition, cortical venous drainage was
      reliably noted in a small subset of patients.

PMID- 14684538
TI  - Intraspinal posterior epidural cysts associated with Baastrup's disease: report
      of 10 patients.
AB  - OBJECTIVE: This study was performed to describe the association of posterocentral
      epidural cysts with interspinous bursal fluid in Baastrup's disease using MRI and
      interspinous bursography. CONCLUSION: Interspinous bursal fluid in Baastrup's
      disease can extend into the posterocentral epidural space and cause various
      degrees of central canal stenosis. Bursography alone or combined with CT allows
      documentation of abnormal communicating channels between the interspinous bursa
      and epidural cyst.

PMID- 14684539
TI  - The MRI appearance of tumefactive demyelinating lesions.

PMID- 14684540
TI  - MDCT compared with digital subtraction angiography for assessment of lower
      extremity arterial occlusive disease: importance of reviewing cross-sectional
      images.
AB  - OBJECTIVE: The aim of our study was to evaluate the efficacy of MDCT angiography
      in the assessment of lower limb peripheral arterial occlusive disease. MATERIALS
      AND METHODS: Twenty-four patients (representing 27 cases) with symptomatic lower
      extremity peripheral arterial occlusive disease underwent both MDCT angiography
      and digital subtraction angiography of the aortoiliac and lower extremity
      arteries. For data analysis, the arterial system was divided into 10 segments.
      Each segment was classified as normal, mildly stenotic, moderately stenotic,
      severely stenotic, or occluded. In evaluating MDCT angiographic findings, cross
      sectional images were mainly observed by scrolling. The diagnostic accuracy of
      MDCT angiography was determined, using digital subtraction angiography as the
      standard reference. The extent of calcification in each segment was also assessed
      on MDCT angiography and was classified as absent, mildly calcified, or severely
      calcified. RESULTS: Of the 480 segments studied, 470 were assessable on both
      digital subtraction angiography and MDCT angiography. On digital subtraction
      angiography, 142 stenoocclusive segments (20 mildly stenotic, 14 moderately
      stenotic, 25 severely stenotic, and 83 occluded) were detected. With regard to
      the detection of segments that had more than mild stenosis, the sensitivity,
      specificity, and accuracy of MDCT angiography were 99.2%, 99.1%, and 99.1%,
      respectively. In the 421 noncalcified and mildly calcified segments, the
      sensitivity, specificity, and accuracy of MDCT angiography for the detection of
      more-than-mild stenosis were 100%, 100%, and 100%, respectively. CONCLUSION: MDCT
      angiography is a reliable method for evaluating the aortoiliac and lower
      extremity arteries.

PMID- 14684541
TI  - Radiofrequency ablation of a symptomatic hepatic cavernous hemangioma.

PMID- 14684542
TI  - N-butyl 2-cyanoacrylate injection via pancreatic collaterals to occlude splenic
      artery distal to large splenic aneurysm after proximal coil embolization.

PMID- 14684543
TI  - MRI for preoperative staging of renal cell carcinoma using the 1997 TNM
      classification: comparison with surgical and pathologic staging.
AB  - OBJECTIVE: The purpose of our study was to determine the accuracy of MRI for
      preoperative staging of renal cell carcinoma using the 1997 TNM classification.
      MATERIALS AND METHODS: We conducted a retrospective review of MRI performed in 40
      consecutive patients with 42 renal cell carcinomas before radical (n = 35) or
      partial (n = 4) nephrectomy or exploratory laparotomy (n = 3). The interval
      between imaging and surgery ranged from 1 to 59 days (mean, 17.9 days). Imaging
      was performed with T1- and T2-weighted, dynamic gadolinium-enhanced, and time-of
      flight sequences. MRI and surgical-pathologic staging was performed using the
      1997 TNM staging system. MRI staging was compared with surgical-pathologic
      staging as the gold standard. Agreement between the two staging methods was
      assessed using the kappa statistic. RESULTS: Agreement between MRI and surgical
      pathologic staging was good for T staging (kappa = 0.72 and 0.78 for reviewers 1
      and 2 respectively), poor for N staging (kappa = 0.13, both reviewers), good for
      M staging (kappa = 0.66, both reviewers), and excellent for the assessment of
      venous involvement (kappa = 0.93, both reviewers). MRI overestimated the T stage
      in five patients and the N stage in five and underestimated the T stage in three,
      the N stage in four, the M stage in one, and the extent of venous thrombosis in
      two patients. CONCLUSION: MRI is a reliable method for preoperative staging of
      renal cell carcinoma using the 1997 TNM classification, in particular for
      assessing venous involvement.

PMID- 14684544
TI  - Incremental benefits of FDG positron emission tomography over CT alone for the
      preoperative staging of ovarian cancer.
AB  - OBJECTIVE: The purpose of this study was to determine whether the addition of
      positron emission tomography (PET) with the radiotracer FDG to cross-sectional
      imaging, such as CT, increases accuracy in the detection of tumor spread.
      SUBJECTS AND METHODS. Fifteen patients who were thought to have ovarian cancer on
      the basis of the results of physical examination, sonography findings, and level
      of serum cancer antigen 125 were enrolled over an 11-month period. After
      screening, patients underwent two imaging examinations-abdominopelvic CT and
      whole-body FDG PET- within 2 weeks before surgery. Also before surgery, staging
      accuracy was assessed separately using CT with or without FDG PET (which was
      based on modifications of the International Federation of Gynecology and
      Obstetrics [FIGO] criteria). The results of the histology and surgery findings
      were used to assess the accuracy of the scanning findings. RESULTS: Staging
      revealed stage III disease in seven patients (IIIC, n = 6; IIIB, n = 1), stage II
      in three (IIC, n = 2; IIB, n = 1), and stage I in five (IC, n = 3; IA, n = 2),
      according to the FIGO criteria. Although CT staging correlated with postoperative
      staging in eight (53%) of 15 patients, consensus evaluation of CT with FDG PET
      staging improved correlation with postoperative staging in 13 (87%) of 15
      patients. CONCLUSION: The addition of FDG PET to CT increases accuracy in staging
      of ovarian cancer.

PMID- 14684546
TI  - Fetal MRI: a developing technique for the developing patient.

PMID- 14684545
TI  - Detection of malignant hepatic tumors with ferumoxides-enhanced MRI: comparison
      of five gradient-recalled echo sequences with different TEs.
AB  - OBJECTIVE: The purpose of our study was to compare the detectability of malignant
      hepatic tumors on ferumoxides-enhanced MRI using five gradient-recalled echo
      sequences at different TEs. MATERIALS AND METHODS: Ferumoxides-enhanced MRIs
      obtained in 31 patients with 50 malignant hepatic tumors (33 hepatocellular
      carcinomas, 17 metastases) were reviewed retrospectively by three independent
      offsite radiologists. T1-weighted gradient-recalled echo images with TEs of 1.4
      and 4.2 msec; T2*-weighted gradient-recalled echo images with TEs of 6, 8, and 10
      msec; and T2-weighted fast spin-echo images of livers were randomly reviewed on a
      segment-by-segment basis. Observer performance was tested using the McNemar test
      and receiver operating characteristic analysis for the clustered data. Lesion-to
      liver contrast-to-noise ratio was also assessed. RESULTS: Mean lesion-to-liver
      contrast-to-noise ratios were negative and lower with gradient-recalled echo at
      1.4 msec than with the other sequences. Sensitivity was higher (p < 0.05) with
      gradient-recalled echo at 6, 8, and 10 msec and fast spin-echo sequences (75-83%)
      than with gradient-recalled echo sequences at 1.4 and 4.2 msec (46-48%), and was
      higher (p < 0.05) with gradient-recalled echo sequence at 8 msec (83%) than with
      gradient-recalled echo at 6 msec and fast spin-echo sequences (75-78%).
      Specificity was comparably high with all sequences (95-98%). The area under the
      receiver operating characteristic curve (A(z)) was greater (p < 0.05) with
      gradient-recalled echo at 6, 8, and 10 msec and fast spin-echo sequences (A(z) =
      0.91-0.93) than with gradient-recalled echo sequences at 1.4 and 4.2 msec (A(z) =
      0.82-0.85). CONCLUSION: In the detection of malignant hepatic tumors, gradient
      recalled echo sequences at 8 msec showed the highest sensitivity and had an A(z)
      value and lesion-to-liver contrast-to-noise ratio comparable with values from
      gradient-recalled echo sequences at 6 and 10 msec and fast spin-echo sequences.

PMID- 14684547
TI  - Congenital tuberculosis in two infants.

PMID- 14684548
TI  - Videofluoroscopic studies of swallowing: need for outcomes research.

PMID- 14684549
TI  - PowerPoint pen.

PMID- 14684550
TI  - Cysts in solid variant of aneurysmal bone cyst.

PMID- 14684551
TI  - Time-resolved 3D MRI of gastric emptying.

PMID- 14684552
TI  - Statistical comparison of proportions.

PMID- 14684553
TI  - Incidental finding of a lipomatous lesion involving the myocardium of the left
      ventricular wall.

PMID- 14684554
TI  - Cisterna chyli: an incidental finding on MR cholangiopancreatography.

PMID- 14684555
TI  - Ectopic cervical thymoma: MRI findings.

PMID- 14684556
TI  - Subungual glomus tumor: emphasis on MR angiography.

PMID- 14684557
TI  - Enhanced pulmonary and systemic response to endotoxin in transgenic sickle mice.
AB  - Some suggest that sickle cell disease (SCD) is associated with a "proinflammatory
      state" that predisposes patients to acute chest syndrome in the setting of
      triggering factors. Conflicting data emerged when inflammation markers in SCD
      were compared with healthy individuals. Therefore, we examined transgenic sickle
      and control mice at baseline and with endotoxin (LPS) intraperitoneal injection
      to determine whether a proinflammatory state truly exists. At baseline, sickle
      mice had elevated levels of circulating leukocytes and soluble vascular cell
      adhesion molecule 1 (sVCAM-1). No other differences were observed at baseline or
      in response to saline. However, LPS challenge was associated with significant
      increases in mortality (p<0.05), airway tone (p<0.03), serum and bronchoalveolar
      lavage levels of cytokines tumor necrosis factor-alpha (p<0.03), interleukin
      1beta (p<0.02), and sVCAM-1 (p<0.01) in sickle mice compared with control
      subjects. Furthermore, 4 hours after LPS, microarray analysis identified 413
      genes differentially expressed in the sickle mice (n=5) compared with only 7 in
      the control subjects (n=5). No difference in lung parenchyma was observed by
      light microscopy. This enhanced response to LPS suggests that the sickle red
      blood cell confers a subclinical "proinflammatory state." This enhanced response
      to inflammatory insult, particularly by adhesion molecules such as sVCAM-1, could
      play a role in the increased susceptibility to pulmonary dysfunction that has
      been observed clinically in SCD.

PMID- 14684558
TI  - The effect of maternal smoking on respiratory and arousal patterns in preterm
      infants during sleep.
AB  - Prenatal exposure to cigarette smoke is associated with an increased risk of
      sudden infant death syndrome. The effect of maternal smoking on apnea and arousal
      patterns in preterm infants is currently unknown. Multichannel polysomnographic
      studies were performed in preterm infants. Thirty infants were enrolled into the
      study: 16 exposed prenatally to cigarette smoke (S) and 14 control infants (C).
      There was no difference in the gestational and postconceptional ages at the time
      of study. Maternal smoking was associated with a significant increase in the
      apneic index in these infants (28.6 +/- 6.4/hour [S] vs. 13.2 +/- 3.9 [C];
      p<0.05), and the difference was noted for obstructive events and only during
      active sleep. The arousal index was significantly decreased in the maternal
      smoking group (34.5 +/- 2.3/hour [S] vs. 46.3 +/- 5.6/hour [C]; p<0.05), with a
      specific decrease in percentage of arousal after respiratory events (10.7 +/-
      2.1% [S] vs. 29.4 +/- 5.4% [C]; p<0.05). In conclusion, preterm infants exposed
      prenatally to cigarette smoke have increased respiratory events during active
      sleep, predominantly due to obstructive apnea, and possibly a higher arousal
      threshold during apneic events. These alterations in respiratory and arousal
      patterns in preterm infants born to smoking mothers may lead to significant
      vulnerability in this population.

PMID- 14684559
TI  - Clustered tuberculosis cases: do they represent recent transmission and can they
      be detected earlier?
AB  - Clustered tuberculosis cases with Mycobacterium tuberculosis isolates showing
      identical restriction fragment length polymorphism patterns are assumed to be the
      result of disease transmission. In a prospective, population-based study in the
      province of North Holland, The Netherlands, we combined molecular methods with
      highly detailed epidemiologic information to determine why many clustered cases
      are not detected at an early stage. Of 481 patients, 138 (29%) fell into 43
      clusters, suggesting recent transmission in 20%. Of 155 patients in clusters
      occurring within 2 years before or after the diagnosis of the disease, 21 (14%)
      had no epidemiologic links with other patients. Independent predictors of the
      absence of such links were female sex and Turkish, Moroccan, or other African
      ethnicity. Of 47 patients with a clear epidemiologic link, 37 (24% of 155) were
      identified early, e.g., by contact tracing, and 10 (6%) were missed. In 85 (55%)
      patients, an epidemiologic link was likely but undetected when using conventional
      contact tracing. Compared with clearly linked patients, only male sex was
      independently associated with presence in this last group. Our results indicate
      that 86% of clustered study patients had epidemiologic links and that
      opportunities for earlier identification using conventional tuberculosis control
      strategies are limited.

PMID- 14684560
TI  - Role of arousals in the pathogenesis of obstructive sleep apnea.
AB  - Arousal is believed to be needed for upper airway opening in obstructive
      hypopneas-apneas, without compelling evidence to support this notion. The
      association may be incidental. I studied the temporal relation between arousal
      and opening and impact of arousal on flow response at opening in 82 patients
      (apnea-hypopnea index, 46 +/- 35/hour). Obstructive apneas-hypopneas were induced
      by dial-down of continuous positive airway pressure. Obstructions and hypopneas
      occurred in 44 and 56% of dial-downs, respectively. When arousal occurred (83% of
      dial-downs), the temporal relation between arousal and opening was inconsistent
      between and within patients. Frequency of opening without or before arousal
      increased with milder obstructions (p < 10(-9)) and with delta power of EEG (p <
      10(-6)). Time of opening was unaffected by whether arousal occurred before or
      after opening (18.0 +/- 9.8 vs. 18.1 +/- 10.5 seconds). Flow response was already
      excessive when opening occurred without or before arousal (180 +/- 148% of
      initial flow decline) and was considerably higher when arousal occurred (267 +/-
      154%, p < 10(-10)). Flow undershoot after first ventilatory response was greater
      if arousal occurred (p < 0.01). It is concluded that arousals are incidental
      events that occur when thresholds for arousal and for arousal-independent opening
      are close. They are not needed to initiate opening or to obtain adequate flow and
      they likely increase the severity of the disorder by promoting greater
      ventilatory instability.

PMID- 14684561
TI  - Effect of treatment with dornase alpha on airway inflammation in patients with
      cystic fibrosis.
AB  - Recombinant human deoxyribonuclease (rhDNase) has been shown to improve lung
      function and reduce the number of pulmonary exacerbations in patients with cystic
      fibrosis (CF), but its long-term effect on airway inflammation remains unknown.
      In this study, we used bronchoalveolar lavage (BAL) to investigate the long-term
      effect of rhDNase on inflammation in patients with CF having mild lung disease. A
      total of 105 patients with CF (> or =5 years of age) having normal lung function
      were randomized to receive rhDNase (2.5 mg/day) or no rhDNase. Patients with a
      normal percentage of neutrophils in BAL fluid at baseline were not randomized and
      served as the control group. The percentage of neutrophils in the pooled BAL
      sample was similar in both randomized groups at baseline. A significant increase
      in neutrophils was observed over the 3-year study period in both untreated
      patients and control subjects, whereas neutrophils remained unchanged in patients
      treated with rhDNase. Elastase activities and interleukin-8 concentrations also
      increased in untreated patients and remained stable in patients on rhDNase. We
      conclude that in patients with CF, an increase in neutrophilic airway
      inflammation is found that is positively influenced by rhDNase treatment.

PMID- 14684562
TI  - Spinal control of erection by glutamate in rats.
AB  - The lumbosacral spinal network controlling penile erection is activated by
      information from peripheral and supraspinal origins. We tested the hypothesis
      that glutamate, released by sensory afferents from the genitals, activates this
      proerectile network. In anesthetized intact and T8 spinalized (i.e., freed from
      supraspinal inhibition) male rats, the parameters of electrical stimulation of
      the dorsal penile nerve (DPN) that elicited intracavernous pressure (ICP) rises
      were determined. In T8 spinalized rats, DPN stimulations were applied in the
      presence of d(-)-2-amino-5-phosphonopentanoic acid (d-AP5), a competitive NMDA
      receptor antagonist, or of 2,3-dioxo-6-nitro-1,2,3,4
      tetrahydrobenzo[f]quinoxaline-7-sulphonamide (NBQX), an AMPA-kainate receptor
      antagonist, injected intrathecally at the lumbosacral level. Both antagonists,
      alone or in combination, dose dependently decreased the ICP rise and increased
      its latency. In conscious rats, reflexive erections were depressed by d-AP5 and
      NBQX, as revealed by an increased latency of the first erection and by decreases
      of the number of rats displaying erections, of the number of erection clusters
      and of the number of erections per cluster. In anesthetized ats, the combined
      administration of the glutamatergic agonists NMDA and AMPA elicited ICP rises in
      the absence of DPN stimulation. In contrast, both agonists moderately decreased
      the ICP rise elicited by DPN stimulation but did not affect its latency. These
      results support our hypothesis that glutamate, released on stimulation of the
      genitals and acting at AMPA and NMDA receptors, is a potent reactivator of the
      spinal proerectile network.

PMID- 14684563
TI  - No effect of dietary calcium on body weight of lean and obese mice and rats.
AB  - Recent epidemiological and animal studies have led to the hypothesis that low
      dietary calcium intakes contribute to obesity. Here, we evaluated whether calcium
      influenced the body weight of normal-weight and obese rodents. All experiments
      involved female C57BL/6J mice or Sprague-Dawley rats fed normal- or high-energy
      density diets (3.8 o 4.7 kcal/g). Calcium intake was manipulated by allowing mice
      to drink sweetened 30 mM CaCl(2) solution or feeding mice and rats diets
      differing in calcium content (0.2%, 0.6%, o 1.8% Ca(2+)). Blood samples were
      taken from rats to confirm that the diets had their intended effects on
      metabolism. There were no effects of the calcium manipulations on energy intake,
      body weight, or carcass fat content and no simple elation between calciotropic
      hormones and body weight. One experiment found a significant decrease in body
      weight gain of lean and obese rats fed the 1.8% Ca(2+) diet, but we suspect that
      this was due to forced consumption of the unpalatable diet, reducing growth.
      These studies provide little support for the hypothesis that dietary calcium
      contributes to the etiology or maintenance of obesity.

PMID- 14684564
TI  - Dysbiosis in inflammatory bowel disease.
AB  - Abundant data have incriminated intestinal bacteria in the initiation and
      amplification stages of inflammatory bowel diseases. However, the precise role of
      intestinal bacteria remains elusive. One theory has suggested a breakdown in the
      balance between putative species of "protective" versus "harmful" intestinal
      bacteria--this concept has been termed "dysbiosis". Arguments in support of this
      concept are discussed.

PMID- 14684565
TI  - Self inflicted rectal ulcer: hearing is believing.

PMID- 14684566
TI  - Helicobacter pylori infection and long term proton pump inhibitor therapy.

PMID- 14684567
TI  - Helminths and harmony.

PMID- 14684568
TI  - Do steroids ameliorate bile acid malabsorption in Crohn's disease?

PMID- 14684569
TI  - Cure of Helicobacter pylori infection in patients with reflux oesophagitis
      treated with long term omeprazole reverses gastritis without exacerbation of
      reflux disease: results of a randomised controlled trial.
AB  - BACKGROUND: Helicobacter pylori gastritis may progress to glandular atrophy and
      intestinal metaplasia, conditions that predispose to gastric cancer. Profound
      suppression of gastric acid is associated with increased severity of H pylori
      gastritis. This prospective randomised study aimed to investigate whether H
      pylori eradication can influence gastritis and its sequelae during long term
      omeprazole therapy for gastro-oesophageal reflux disease (GORD). METHODS: A total
      of 231 H pylori positive GORD patients who had been treated for > or =12 months
      with omeprazole maintenance therapy (OM) were randomised to either continuation
      of OM (OM only; n = 120) or OM plus a one week course of omeprazole, amoxycillin,
      and clarithromycin (OM triple; n = 111). Endoscopy with standardised biopsy
      sampling as well as symptom evaluation were performed at baseline and after one
      and two years. Gastritis was assessed according to the Sydney classification
      system for activity, inflammation, atrophy, intestinal metaplasia, and H pylori
      density. RESULTS: Corpus gastritis activity at entry was moderate or severe in
      50% and 55% of the OM only and OM triple groups, respectively. In the OM triple
      group, H pylori was eradicated in 90 (88%) patients, and activity and
      inflammation decreased substantially in both the antrum and corpus (p<0.001,
      baseline v two years). Atrophic gastritis also improved in the corpus (p<0.001)
      but not in the antrum. In the 83 OM only patients with continuing infection,
      there was no change in antral and corpus gastritis activity or atrophy, but
      inflammation increased (p<0.01). H pylori eradication did not alter the dose of
      omeprazole required, or reflux symptoms. CONCLUSIONS: Most H pylori positive GORD
      patients have a corpus predominant pangastritis during omeprazole maintenance
      therapy. Eradication of H pylori eliminates gastric mucosal inflammation and
      induces regression of corpus glandular atrophy. H pylori eradication did not
      worsen reflux disease or lead to a need for increased omeprazole maintenance
      dose. We therefore recommend eradication of H pylori in GORD patients receiving
      long term acid suppression.

PMID- 14684571
TI  - Oesophageal clearance of acid and bile: a combined radionuclide, pH, and Bilitec
      study.
AB  - BACKGROUND: Studies combining pH and Bilitec monitoring found a high prevalence
      of both acid and duodeno-gastro-oesophageal reflux in severe reflux disease.
      Clearance of refluxed material is a major defence mechanism against reflux.
      Several studies have been devoted to oesophageal acid clearance but oesophageal
      clearance of refluxed duodenal contents (DC) has rarely been addressed. AIM: To
      compare oesophageal acid and DC clearance. METHODS: Ten healthy volunteers (five
      women, mean age 23 (1) years) were studied. Firstly, a balloon tip catheter,
      positioned in the duodenum under fluoroscopy, was used to aspirate DC after
      stimulation by a high caloric liquid meal (200 ml, 300 kcal). During the second
      session, pH and Bilitec probes were positioned 5 cm above the lower oesophageal
      sphincter and a small infusion catheter was introduced into the proximal
      oesophagus. The subject was placed supine under a gamma camera. One of two
      different solutions (DC mixed with 0.2 mCi Tc99m pertechnetate or citric acid (pH
      2) mixed with 0.2 mCi Tc99m pertechnetate) was infused into the proximal
      oesophagus and the subject was instructed to swallow at 20 second intervals.
      Clearance was assessed using scintigraphy (dynamic acquisition, one frame per
      second in the anterior view; calculation of time to clear peak counts to
      background level), pH (time to pH<4) or Bilitec (time absorbance >0.14)
      monitoring, with or without continuous saliva aspiration. Each condition was
      studied twice in a randomised design; measurement time was four minutes,
      interrupted by water flushing, with a two minute rest period. Results are given
      as mean (SEM) and were compared by Student's t test and Pearson correlation.
      RESULTS: Scintigraphic evaluation showed a volume clearance time of 29 (3)
      seconds for acid and 28 (9) seconds for DC (NS). Saliva aspiration had no
      significant influence on volume clearance of acid or DC (28 (4) and 30 (13)
      seconds, respectively; NS). pH monitoring showed an acid clearance time of 217
      (15) seconds, which was significantly prolonged to 324 (30) seconds during saliva
      aspiration (p<0.05). Bilitec monitoring showed a DC clearance time of 131 (27)
      seconds, which was not significantly prolonged by saliva aspiration (176 (36)
      seconds; p = 0.08). DC clearance was faster than acid clearance, either without
      or with saliva aspiration (p<0.055 and p<0.05, respectively). CONCLUSIONS: Under
      experimental conditions, liquid acid and DC solutions have comparable volume
      clearances. Chemical clearance occurs slightly faster for DC than for acid, and
      saliva plays a major role in the clearance of acid only.

PMID- 14684572
TI  - Expression of cyclooxygenase 2, microsomal prostaglandin E synthase 1, and EP
      receptors is increased in rat oesophageal squamous cell dysplasia and Barrett's
      metaplasia induced by duodenal contents reflux.
AB  - BACKGROUND AND AIM: It is known that bile acids can induce mucosal injury,
      stimulate cell proliferation, and promote tumorigenesis. A large body of genetic
      and biochemical evidence indicate that the biosynthetic pathway of prostaglandin
      E2 (PGE2) may play an important role in human and rodent tumours. Therefore, we
      examined the expression pattern of cyclooxygenase 1 (COX-1), COX-2, and
      microsomal prostaglandin E synthase 1 (mPGES-1), as well as EP receptor subtypes
      in rat oesophageal lesions induced by duodenal contents reflux. METHODS:
      Oesophagoduodenal anastomosis was performed in rats to induce duodenal contents
      reflux. We examined histological changes and expression of COX-1, COX-2, mPGES-1,
      and EP receptor subtypes in the oesophagus by immunohistochemistry and reverse
      transcription-polymerase chain reaction. RESULTS: Normal control oesophageal
      tissues showed COX-1 expression in subepithelial stromal cells, including
      endothelial cells and muscular cells, and did not reveal expression of COX-2 or
      mPGES-1. In the case of squamous cell lesions, immunoreactivity of COX-1 was
      similar to that of normal lesions, and COX-2 was maximally expressed around the
      vascular papillae of tissues showing dysplasia and surrounding epithelial layer
      and basal layer. mPGES-1 was highly expressed in stromal cells with COX-2
      expression. In the case of Barrett's oesophagus, COX-2 and mPGES-1 were
      predominantly in subepithelial stromal cells. mRNA levels of COX-2, mPGES-1, EP2,
      EP3, and EP4 were higher in the experimental groups than in controls.
      CONCLUSIONS: We suggest that the biosynthetic pathway of PGE2 may play an
      important role in oesophageal squamous cell dysplasia and glandular metaplasia
      induced by duodenal contents reflux.

PMID- 14684574
TI  - Lysine kinetics in preterm infants: the importance of enteral feeding.
AB  - INTRODUCTION: Lysine is the first limiting essential amino acid in the diet of
      newborns. First pass metabolism by the intestine of dietary lysine has a direct
      effect on systemic availability. We investigated whether first pass lysine
      metabolism in the intestine is high in preterm infants, particularly at a low
      enteral intake. PATIENTS AND METHODS: Six preterm infants (birth weight 0.9 (0.1)
      kg) were studied during two different periods: period A (n = 6): 40% of intake
      administered enterally, 60% parenterally; lysine intake 92 (6) micromol/(kg x h);
      and period B (n = 4): 100% enteral feeding; lysine intake 100 (3) micromol/(kg x
      h). Dual stable isotope tracer techniques were used to assess splanchnic and
      whole body lysine kinetics. RESULTS: Fractional first pass lysine uptake by the
      intestine was significantly higher during partial enteral feeding (period A 32
      (10)% v period B 18 (7)%; p<0.05). Absolute uptake was not significantly
      different. Whole body lysine oxidation was significantly decreased during full
      enteral feeding (period A 44 (9) v period B 17 (3) micromol/(kg x h); p<0.05) so
      that whole body lysine balance was significantly higher during full enteral
      feeding (period A 52 (25) v period B 83 (3) micromol/(kg x h); p<0.05).
      CONCLUSIONS: Fractional first pass lysine uptake was much higher during partial
      enteral feeding. Preterm infants receiving full enteral feeding have lower whole
      body lysine oxidation, resulting in a higher net lysine balance, compared with
      preterm infants receiving partial enteral feeding. Hence parenterally
      administered lysine is not as effective as dietary lysine in promoting protein
      deposition in preterm infants.

PMID- 14684573
TI  - Long term outcome of patients with gastric marginal zone B cell lymphoma of
      mucosa associated lymphoid tissue (MALT) following exclusive Helicobacter pylori
      eradication therapy: experience from a large prospective series.
AB  - BACKGROUND: Helicobacter pylori plays a decisive role in the pathogenesis of
      gastric marginal zone B cell lymphoma of mucosa associated lymphoid tissue
      (MALT), and eradication therapy has become a widely accepted initial treatment of
      stage I disease. OBJECTIVE: To determine the long term outcome of patients
      undergoing exclusive H pylori eradication therapy. DESIGN: A prospective series
      of patients with newly diagnosed marginal zone B cell lymphoma of MALT. SETTING:
      Multicentre study in Germany and Austria. PATIENTS: Ninety five patients; 90 of
      these (five lost to follow up) with a mean age of 54.3 (27-85) years were
      followed up for at least 12 months. INTERVENTION: Complete staging work up
      revealing stage I disease and H pylori infection. Patients received triple
      therapy (OMC: omeprazole 20 mg twice daily, metronidazole 400 mg twice daily, and
      clarithromycin 250 mg twice daily; or OAC: omeprazole 20 mg twice daily,
      amoxycillin 1000 mg twice daily, and clarithromycin 500 twice daily) for one
      week. RESULTS: Median follow up was 44.6 (12-89) months. H pylori was
      successfully eradicated in 88 patients (98%); in two patients eradication therapy
      failed. Long term outcome was characterised by complete regression of lymphoma in
      56 patients (62%), minimal residual disease in 17 patients (18%), partial
      remission in 11 patients (12%), no change in four patients (4%), and progressive
      disease in two patients (2%). Four patients with complete remission relapsed
      after 6, 8, 8, and 15 months, one revealing reinfection by H pylori. Regression
      rate was higher in stage I1 disease compared with stage I2, as diagnosed by
      endoscopic ultrasound. CONCLUSION: The majority of patients with low grade
      gastric MALT lymphoma treated by exclusive H pylori eradication have a favourable
      long term outcome, offering a real chance of cure.

PMID- 14684575
TI  - Ferroportin/IREG-1/MTP-1/SLC40A1 modulates the uptake of iron at the apical
      membrane of enterocytes.
AB  - BACKGROUND: Absorption of non-haeme iron occurs mainly in the duodenum. It
      involves the divalent metal transporter 1 (DMT1) in the uptake of ferrous Fe(II)
      iron and the basolateral transporter ferroportin/IREG-1/MTP-1/SLC40A1 in its
      release. Whether ferroportin functions in this process at other sites in the
      enterocyte is unknown. In this study the effect of a blocking antibody to
      ferroportin on the uptake and release of iron was evaluated in enterocyte-like
      cells (IEC-6 and Caco-2) and in freshly isolated duodenal enterocytes from rats.
      METHODS: Uptake of 1 microM Fe(II) and its release by cells was studied in the
      presence of the antibody. Ferroportin expression was determined by western blot
      analysis of duodenal mucosa enriched microvillus membranes, Caco-2 cells, IEC-6
      cells, and freshly isolated enterocytes. Immunofluorescent detection of
      ferroporitn was performed on frozen sections of duodenum from rats with
      variations in body iron stores. RESULTS: Ferroportin was expressed in all cell
      types. In these cells, the antibody significantly reduced (p<0.05) uptake of
      Fe(II) by 40-50% but had no effect on the release of iron. In Caco-2 cells,
      Fe(II) uptake was reduced only when the antibody was in contact with the apical
      membrane. Ferroportin protein was enriched in microvillus membrane preparations.
      In enterocytes from iron deficient rats, ferroportin was expressed along the
      brush border where it colocalised with lactase. Ferroportin was seen in the basal
      cytoplasm and along the basolateral membranes. Iron loading markedly reduced
      intracellular expression of ferroportin. In Caco-2 cells, ferroportin also
      localised to the microvillus and lateral and basal membranes. CONCLUSIONS: In
      addition to release, ferroportin functions in the uptake of iron at the apical
      membrane, possibly by modulating the activity of DMT1.

PMID- 14684576
TI  - Intracellular potentiation between two second messenger systems may contribute to
      cholera toxin induced intestinal secretion in humans.
AB  - BACKGROUND: Cholera toxin (CT) acts on intestinal epithelial cells both directly
      and indirectly via activation of a secretory neural reflex. The reflex may
      release acetylcholine as one of its final neurotransmitters. This opens up the
      possibility of a third mechanism of action for CT, namely a synergistic
      interaction between two secretagogues acting on different second messenger
      systems within the epithelial cell. AIMS: To establish evidence for cholinergic
      innervation to human ileal epithelial cells and to investigate whether CT
      potentiates the action of acetylcholine on human intestinal epithelial cells.
      METHODS: Transverse sections of human ileum were examined for mucosal cholinergic
      nerves and M3 muscarinic receptors using antibodies raised to choline
      acetyltransferase and M3 receptors. Short circuit current (Isc) responses and ion
      flux movements were elicited from T84 epithelial cell monolayers set up in Ussing
      chambers. RESULTS: Immunohistochemistry of native human ileal mucosa revealed the
      presence of both cholinergic nerves and muscarinic M3 receptors located to the
      basolateral domain of epithelial cells. Secretory responses of T84 cell
      monolayers to acetylcholine were greatly potentiated in the presence of CT. This
      effect, substituting forskolin for CT, was mirrored by increases in basolateral
      86Rb and apical 125I efflux. Charybdotoxin plus apamin reduced both Isc and 86Rb
      efflux evoked by acetylcholine, in the presence of forskolin. CONCLUSIONS: Human
      ileal mucosa receives a direct cholinergic innervation to its epithelial cells.
      Secretory effects of acetylcholine on epithelial cells are augmented in the
      presence of CT. Such a synergistic response is dependent on optimum opening of
      basolateral potassium channels by acetylcholine and apical chloride channels by
      CT. The interaction may contribute to the mechanism of action of cholera toxin
      induced secretory diarrhoea.

PMID- 14684577
TI  - A novel method for rapidly diagnosing the causes of diarrhoea.
AB  - BACKGROUND: The microbiological diagnosis of infectious diarrhoea may take
      several days using conventional techniques. In order to determine whether flatus
      can be used to make a rapid diagnosis, the volatile organic compounds associated
      with diarrhoea were analysed. METHODS: Stool samples were collected from 35
      patients with infectious diarrhoea and from six healthy controls. Gaseous
      compounds were extracted from a headspace using solid phase microextraction and
      analysed using gas chromatography and mass spectroscopy. RESULTS: Characteristic
      patterns of volatile gases were found for the main causes of infectious diarrhoea
      in hospitals. Furan species without indoles indicated Clostridium difficile,
      ethyl dodecanoate indicated rotavirus, ammonia without ethyl dodecanoate
      suggested other enteric viruses, and the absence of hydrocarbons and terpenes
      indicated Campylobacter infection. CONCLUSION: These results could be the basis
      of rapid near patient diagnosis of infectious diarrhoea.

PMID- 14684578
TI  - Acute dehydrating disease caused by Vibrio cholerae serogroups O1 and O139 induce
      increases in innate cells and inflammatory mediators at the mucosal surface of
      the gut.
AB  - BACKGROUND AND AIMS: The general concept is that as Vibrio cholerae is not
      invasive, it mediates a non-inflammatory type of infection. This is being re
      evaluated based on available data that natural cholera infection or cholera toxin
      induces a Th2-type of immune profile and stimulates the humoral immune response,
      innate cells, and mediators in the host. METHODS: To perform a comprehensive
      analyses of the inflammatory components, we studied mucosal biopsies from
      patients, both adults and children with acute watery diarrhoea caused by V
      cholerae O1 and O139. Patients with cholera, adults (n = 30) and children (n =
      18), as well as healthy controls (n = 24) were studied. Histochemical,
      immunohistochemical, and ultrastructural studies were carried out to elucidate
      the contribution of the different factors using paraffin and frozen duodenal
      and/or rectal sections as appropriate. Samples were collected during the acute
      stage and during early and/or late convalescence. RESULTS: Following natural
      cholera infection, patients responded with increases in neutrophil polymorphs
      during the acute stage (p<0.001) compared with healthy controls whereas mucosal
      mast cells (MMC) (p = 0.008) and eosinophils (p = 0.034) increased in the gut
      during convalescence. Electron microscopic analyses of duodenal biopsies from
      adult patients showed increased piecemeal degranulation in both MMC and
      eosinophils and accumulation of lipid bodies in MMC. Duodenal biopsies from V
      cholerae O1 infected patients showed upregulation of myeloperoxidase,
      lactoferrin, PGHS-1, SCF, tryptase, tumour necrosis factor alpha, alpha-defensin,
      and eotaxin during the acute stage and chymase, interleukin 3 and major basic
      protein during convalescence. CONCLUSION: We have shown that innate cells and
      their mediators are upregulated in acute watery diarrhoea. These cells and
      factors of the innate arm may be important in the host's defence against cholera.
      Such effects may need to be simulated in a vaccine to achieve long lasting
      protection from cholera.

PMID- 14684579
TI  - Defective mucosal T cell death is sustainably reverted by infliximab in a caspase
      dependent pathway in Crohn's disease.
AB  - BACKGROUND AND AIMS: To verify whether targeting defective mucosal T cell death
      underlies the sustained therapeutic benefit of infliximab in Crohn's disease, we
      explored its in vivo proapoptotic effect after 10 weeks of treatment, and its in
      vitro killing activity on lamina propria T cells (LPT) and peripheral blood T
      cells (PBT), both isolated from Crohn's disease patients. METHODS: Endoscopic
      intestinal biopsies were collected from 10 Crohn's disease patients (six steroid
      refractory and four fistulising) before and after three consecutive infusions of
      infliximab, administered at week 0, 2, and 6 in a single intravenous dose (5
      mg/kg), and from 10 subjects who proved to have functional diarrhoea. Apoptosis
      was determined in vivo by TUNEL assay, and in vitro by fluorescein isothiocyanate
      annexin V/propidium iodide staining on LPT and PBT from Crohn's disease patients
      cultured with infliximab. The effect of the broad caspase inhibitor Z-VAD-FMK and
      the neutralising anti-Fas antibody ZB4 was tested in vitro on LPT and PBT treated
      with infliximab. Caspase-3 activity was determined by immunoblotting. RESULTS: In
      Crohn's disease patients, infliximab treatment induced a sustained LPT apoptosis,
      still evident four weeks after the last infusion. In vitro infliximab induced
      death of LPT from Crohn's disease patients occurred via apoptosis rather than
      necrosis. LPT showed a higher susceptibility to infliximab induced apoptosis than
      PBT in Crohn's disease patients. The signalling pathway underlying the
      restoration of infliximab induced LPT apoptosis occurred via the caspase pathway
      but not Fas-Fas ligand interaction in Crohn's disease. CONCLUSIONS: These
      findings demonstrate that apoptosis is the major mechanism by which infliximab
      exerts its killing activity on LPT in Crohn's disease. The sustained LPT
      proapoptotic action of infliximab, which extends far beyond its circulating half
      life, may be responsible for the sustained remission induced in Crohn's disease
      patients by infliximab retreatment.

PMID- 14684580
TI  - Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the
      glucocorticoid receptor.
AB  - BACKGROUND: Patients with Crohn's disease suffer from intestinal bile acid
      malabsorption. Intestinal bile acid absorption is mediated by the apical sodium
      dependent bile acid transporter ASBT/IBAT (SLC10A2). In rats, ASBT is induced by
      glucocorticoids. AIMS: To study whether human ASBT is activated by
      glucocorticoids and to elucidate the mechanism of regulation. PATIENTS AND
      METHODS: ASBT expression in ileal biopsies from patients with Crohn's disease and
      from healthy subjects was quantified by western blot. ASBT promoter function was
      studied in luciferase assays and by electrophoretic mobility shift assay.
      RESULTS: In 16 patients with Crohn's disease, ASBT expression was reduced to 69
      (7.5)% compared with healthy controls (mean (SEM); p = 0.01). In 10 healthy male
      volunteers, ASBT protein expression was increased 1.34 (0.11)-fold (mean (SEM);
      p<0.05) after 21 days' intake of budesonide (9 mg/day) whereas expression of the
      peptide transporter 1 was unaffected. Reporter constructs of the human ASBT
      promoter were activated 15-20-fold by coexpression of the glucocorticoid receptor
      (GR) and exposure to the GR ligands dexamethasone or budesonide. Two
      glucocorticoid response elements in the ASBT promoter, arranged as inverted
      hexanucleotide repeats (IR3 elements), conferred inducibility by GR and
      dexamethasone in a heterologous promoter context and were shown to bind GR in
      mobility shift assays. CONCLUSIONS: Human ASBT is induced by glucocorticoids in
      vitro and in vivo. Induction of ASBT by glucocorticoids could be beneficial in
      patients with Crohn's disease who exhibit reduced ASBT expression. This study
      identifies ASBT as a novel target of glucocorticoid controlled gene regulation in
      the human intestine.

PMID- 14684581
TI  - Reversal of abnormal collagen production in Crohn's disease intestinal biopsies
      treated with regenerating agents.
AB  - BACKGROUND: Crohn's disease (CD) is characterised by inflammation, muscle layer
      overgrowth, and collagenous fibrosis of the intestinal tract, with no effective
      therapy against collagen accumulation. AIMS: We quantified production of collagen
      in resection specimens from normal and CD patients and investigated the effect of
      regenerating agents (RGTAs) on collagen production. RGTAs are chemically
      substituted dextrans engineered to mimic the growth factor protecting effects of
      heparan sulphates. RGTAs have been shown to enhance tissue repair in various in
      vivo models and to modulate in vitro collagen phenotype differentially according
      to their structure. PATIENTS: We studied intestinal biopsies from two groups of
      CD patients: treated with glucocorticoids (CD-GC group: 10 patients) or not
      treated (CD group: seven patients), and from seven control patients. METHODS:
      After 24 hours of ex vivo incubation with (3H) proline, collagen I, III, and V
      were extracted by pepsin and quantitatively separated by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis. Biosynthesis of each collagen type was
      quantified on radiolabelled isolated collagen. RESULTS: Total intestinal collagen
      production in CD patients compared with controls was increased up to 3.5-fold
      overall (p<0.001). In particular, collagen III biosynthesis was enhanced by 6.2
      fold (p<0.001) in CD patients. In the CD-GC group, collagen production
      abnormalities were less marked. RGTAs added to the incubation medium in the CD
      group decreased total collagen production by 50% and decreased collagen III
      synthesis by 76%. CONCLUSION: This finding offers a rationale for using RGTAs in
      the treatment of intestinal fibrosis in CD, thus opening up a potential new
      therapeutic field for this family of drugs.

PMID- 14684582
TI  - Systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn's
      disease differentially activate the innate immune response.
AB  - BACKGROUND AND AIMS: The mucosa in ulcerative colitis (UC) is replete with
      antibody producing plasma B cells and polymorphonuclear leucocytes (PMN). This
      combination of effector cells requires a crosslinking antigen to evoke an
      antibody driven PMN inflammatory response via their Fc receptors. The stimulus
      for activation is thought to be commensal bacteria colonising the gut mucosa. The
      aim of this investigation was to compare the principal culturable bacterial
      populations on the rectal mucosa of UC patients, and to determine whether
      specific antibodies towards these bacteria can activate infiltrating PMN through
      opsonisation. This would provide an explanation for this chronic inflammatory
      condition. METHODS: Bacteria colonising rectal tissue were characterised using
      chemotaxonomic techniques. Systemic antibody responses were measured against
      total antigens and surface antigens of these organisms in UC and Crohn's disease
      (CD) patients, together with healthy controls. Antibody enhancement of the
      respiratory burst in PMN was also investigated, against a range of mucosal
      isolates. RESULTS: Distinct differences were observed in some bacterial
      populations in UC biopsies, which were generally reflected in antibody responses
      towards these organisms. UC patients had higher IgG responses to surface
      antigens, primarily IgG1, whereas the response in CD was mainly IgG2. Antibodies
      from UC patients greatly enhanced the respiratory burst in PMN, in response to
      individual bacterial species. CONCLUSIONS: Changes in mucosal bacteria, and a
      switch from internal to surface antigen/antibody reactivity of a predominantly
      IgG1 type, leads to greater opsonisation of the respiratory burst in PMN,
      providing a mechanism for maintaining the inflammatory state in UC.

PMID- 14684583
TI  - Concurrent infection with Schistosoma mansoni attenuates inflammation induced
      changes in colonic morphology, cytokine levels, and smooth muscle contractility
      of trinitrobenzene sulphonic acid induced colitis in rats.
AB  - BACKGROUND AND AIMS: Crohn's disease, characterised by chronic T helper 1 (Th1)
      inflammation and dysmotility of the gut, is most prevalent in developed
      countries. Parasitic infections are most prevalent in developing countries and
      induce a T helper 2 (Th2) immune response. We hypothesised that this Th2 immune
      response protects against Th1 gut inflammation. METHODS: The parasite Schistosoma
      mansoni induces a transient Th2 immune response in the semipermissive rat host.
      2,4,6-Trinitrobenzene sulphonic acid (TNBS) induced colitis is an experimental
      model of Th1-like gut inflammation. The effect of concurrent infection with S
      mansoni on the course of TNBS induced colitis was assessed using macroscopic and
      microscopic damage scores, histology, myeloperoxidase (MPO) activity assay,
      cytokine production assay, and by studying in vitro contractility of longitudinal
      and circular colonic muscle strips. RESULTS: TNBS induced colitis that
      spontaneously healed after four weeks. Concurrent infection with S mansoni
      significantly reduced the duration of TNBS induced colitis to two weeks, as shown
      by macroscopic and microscopic damage scores and by a faster decrease in colonic
      MPO activity. TNBS increased colonic interleukin 2 (IL-2) production whereas S
      mansoni increased splenic IL-4 and IL-2 levels. Contractility of longitudinal and
      circular muscle strips was maximally inhibited one week after TNBS and normalised
      after three weeks. After four weeks, longitudinal muscle strip contractility was
      significantly increased. Concurrent infection with S mansoni normalised
      longitudinal muscle contractility after one week whereas circular muscle
      contractility remained inhibited. CONCLUSIONS: Concurrent infection with S
      mansoni significantly attenuates TNBS induced colitis in the rat. Inflammation
      induced disturbances in contractility of longitudinal and circular colonic muscle
      strips may outlast the inflammatory reaction.

PMID- 14684584
TI  - Once daily high dose probiotic therapy (VSL#3) for maintaining remission in
      recurrent or refractory pouchitis.
AB  - BACKGROUND: Ten to 15% of patients with pouchitis experience refractory or
      recurrent disease. The aim of this study was to evaluate the effectiveness of a
      single daily high dose probiotic preparation (VSL#3) in maintaining antibiotic
      induced remission, and quality of life (QOL), for one year in such patients.
      METHODS: Patients with pouchitis at least twice in the previous year or requiring
      continuous antibiotics, associated with a pouchitis disease activity index (PDAI)
      > or =7 (0 = perfect; 18 = worst), in whom remission was induced by four weeks of
      combined metronidazole and ciprofloxacin, were randomised to receive VSL#3 6 g or
      placebo once daily for one year or until relapse. Symptomatic, endoscopic, and
      histological evaluations were made before, and two and 12 months after
      randomisation or at the time of relapse. Remission was defined as a clinical PDAI
      < or =2 and endoscopic PDAI < or =1. Relapse was defined as an increased clinical
      PDAI score > or =2 and increased endoscopic PDAI score > or =3. QOL was assessed
      using the inflammatory bowel disease questionnaire (IBDQ). RESULTS: Thirty six
      patients were randomised: 20 to VSL#3 and 16 to placebo. Remission was maintained
      at one year in 17 patients (85%) on VSL#3 and in one patient (6%) on placebo
      (p<0.0001). The IBDQ score remained high in the VSL#3 group (p = 0.3) but
      deteriorated in the placebo group (p = 0.0005). CONCLUSION: The once daily high
      dose probiotic VSL#3 is effective in maintaining antibiotic introduced remission
      for at least a year in patients with recurrent or refractory pouchitis. This is
      associated with a high level of quality of life.

PMID- 14684585
TI  - Aetiology of colorectal cancer and relevance of monogenic inheritance.
AB  - BACKGROUND AND AIMS: Although diet and lifestyle are associated with the
      development of colorectal malignancies, the only clearly identified aetiological
      factors in colorectal cancer are inheritance (hereditary non-polyposis colorectal
      cancer (HNPCC) and familial polyposis), inflammatory bowel diseases,
      papillomavirus, and acquired immunodeficiency syndrome (AIDS). Our aim was to
      determine what proportion of colorectal neoplasms could be attributed to these
      specific factors. PATIENTS AND METHODS: Data from a colorectal cancer registry
      were analysed over a 15 year period, during which nearly 2500 cases were
      recorded. In patients with suspected HNPCC, microsatellite instability and
      immunohistochemical expression of proteins encoded by the main DNA mismatch
      repair genes were assessed. In families with unstable neoplasms, constitutional
      mutations of the mismatch repair genes hMSH2, hMLH1, and hMSH6 were evaluated by
      single strand conformation polymorphism analysis and sequencing. RESULTS:
      Inflammatory bowel diseases, familial polyposis, and AIDS were rare causes of
      colorectal cancer (three, three, and one case, respectively). Anal squamous
      carcinoma developed in 27 patients (1.0%) and could be attributed to
      papillomavirus infection. In 58 patients (from 34 families) a clinical diagnosis
      of HNPCC was established (2.4%). In total, cases with a known aetiology were 92
      (3.7% of all patients). Microsatellite instability was detected in 15 cancers
      from HNPCC families, and germline mutations in six families (12 patients, 0.5% of
      the total). Families with unstable tumours, with or without mutations, were
      clinically similar, suggesting the involvement of the mismatch repair system even
      when mutations were not detected. CONCLUSIONS: The study suggests that the
      aetiology of colorectal malignancies remains elusive in the large majority of
      cases. Among specific causes, HNPCC represents the most frequent. However, with a
      population based approach, constitutional mutations of the main genes involved in
      HNPCC can be detected in only 20% of cases.

PMID- 14684586
TI  - Regulation of epidermal growth factor receptor in human colon cancer cell lines
      by interferon alpha.
AB  - BACKGROUND AND AIM: The biology of growth factor receptor expression has
      implications for receptor specific cancer therapy. In this study, we examined:
      (a) regulation of epidermal growth factor receptor (EGFR) expression in a panel
      of 10 human colon cancer cell lines using interferon alpha (IFN-alpha); (b)
      ability of IFN-alpha to inhibit cell proliferation; and (c) sensitivity of IFN
      alpha pretreated cells to EGF. METHODS: Cell proliferation was measured both by
      crystal violet colorimetric and clonogenic assays. Cell surface, intracellular,
      and/or total cell protein expression of EGFR was assessed by indirect
      immunofluorescence flow cytometry and/or fluorescein isothiocyanate (FITC)-EGF
      binding and internalisation flow cytometric assay. RESULTS: IFN-alpha treatment
      upregulated expression of cell surface EGFR in seven of 10 colon cancer cell
      lines within 16 hours, reaching a peak within 48-96 hours; this was accompanied
      by transient elevation of intracellular EGFR and marked growth inhibition. IFN
      alpha treated cancer cells were still sensitive to EGF proliferative stimulation.
      CONCLUSIONS: Our results indicate that cytostatic concentrations of IFN-alpha can
      enhance cell surface and intracellular EGFR expression in a proportion of human
      colon cancer cells. The antiproliferative action of IFN-alpha could not block the
      signal transduction of the EGF-EGFR pathway. This may have clinical implications
      for improving treatment based on targeting of EGFR.

PMID- 14684587
TI  - Randomised, double blind, placebo controlled trial of interferon, ribavirin, and
      amantadine versus interferon, ribavirin, and placebo in treatment naive patients
      with chronic hepatitis C.
AB  - BACKGROUND AND AIM: In this study, we compared the efficacy of triple therapy
      (interferon alfa, ribavirin, and amantadine) with standard therapy (interferon
      alfa and ribavirin) in treatment naive patients with chronic hepatitis C virus
      (HCV). METHODS: In this prospective, randomised, double blind, placebo
      controlled, multicentre study, 85 patients (amantadine group) received a three
      drug regimen of interferon alfa-2b 3 million units three times per week,
      ribavirin 1000-1200 mg daily in divided doses, and amantadine 100 mg twice daily,
      and 86 patients (placebo group) received interferon alfa-2b, ribavirin, and
      identical placebo. Treatment was discontinued at 24 weeks if patients had
      detectable HCV RNA by polymerase chain reaction (PCR). All patients were followed
      for 24 weeks after completion of treatment. The primary end point was
      undetectable HCV-RNA by PCR at 24 weeks (sustained viral clearance) after
      completion of treatment. RESULTS: At the end of treatment, HCV RNA clearance was
      seen in 32.9% of the amantadine group and 38.4% of the placebo group (p=0.3).
      Sustained virological response was seen in 24.7% of the amantadine group and in
      27.9% of the placebo group by intention to treat analysis; response rate was
      30.4% and 34.8%, respectively, in those who completed 24 weeks of treatment. Poor
      response was seen in both groups among cirrhotics, African-Americans, genotype 1,
      and those with a higher viral load. By multivariate analysis, genotype 1, high
      viral load, and low serum albumin were the only predictors of poor response.
      Addition of amantadine to the standard regimen did not result in any unexpected
      side effects. CONCLUSION: Response to triple therapy of interferon alfa,
      ribavirin, and amantadine was similar to standard therapy of interferon alfa and
      ribavirin. Our results suggest that amantadine has no role in the management of
      HCV.

PMID- 14684588
TI  - Cholesterol synthesis inhibition distal to squalene upregulates biliary
      phospholipid secretion and counteracts cholelithiasis in the genetically prone
      C57L/J mouse.
AB  - BACKGROUND AND AIMS: Newly synthesised cholesterol contributes poorly to biliary
      lipid secretion but may assume greater importance when the rate limiting enzyme 3
      hydroxy-3-methylglutaryl-CoA reductase (HMGR) is upregulated. As this occurs in
      the gall stone susceptible C57L/J inbred mouse, we employed two cholesterol
      biosynthesis inhibitors, Tu 2208 and Ro 48-8071, potent inhibitors of squalene
      epoxidase and oxidosqualene-lanosterol cyclase, respectively, to assess their
      potential in preventing cholesterol cholelithiasis in the C57L/J mouse strain.
      Mice were fed a lithogenic diet comprising a balanced nutrient intake with 15%
      dairy fat, 1% cholesterol, and 0.5% cholic acid added. METHODS: We determined
      gall stone phenotype, HMGR activity, biliary lipid secretion rates, and
      counterregulatory events in male C57L/J mice and gall stone resistant AKR treated
      with Tu 2208 (30-60 mg/kg/day) or Ro 48-8071 (30-100 mg/kg/day), while ingesting
      chow or the lithogenic diet. RESULTS: Both agents reduced the gall stone
      prevalence rate from 73% to 17% in C57L/J mice, inhibited HMGR activity, and
      decreased hepatic cholesterol concentrations without appreciably influencing
      biliary cholesterol secretion. In C57L as well as AKR mice, both agents increased
      biliary phospholipid (which is mostly phosphatidylcholine) secretion rates and at
      the highest doses effectively reduced the biliary cholesterol saturation index.
      CONCLUSIONS: Cholesterol biosynthesis inhibitors acting distally to squalene do
      not reduce biliary cholesterol secretion rates despite reductions in cholesterol
      biosynthesis and hepatocellular levels. However, they effectively prevent gall
      stone formation through stimulation of pathways that lead to enhanced biliary
      phospholipid secretion.

PMID- 14684589
TI  - Monitoring target reduction in hepatic venous pressure gradient during
      pharmacological therapy of portal hypertension: a close look at the evidence.
AB  - Recurrent variceal bleeding is very frequent after variceal haemorrhage and
      pharmacological therapy is the first choice treatment. Recently, baseline and
      repeat measurements of hepatic venous pressure gradient (HVPG) have been
      considered necessary to optimally manage patients receiving pharmacological
      therapy so as to reduce the frequency of rebleeding. However, the clinical
      validity and applicability of monitoring for target HVPG reductions is not
      sufficiently proven and needs to be specifically evaluated in a prospective
      trial.

PMID- 14684590
TI  - Undiagnosed coeliac disease does not appear to be associated with unfavourable
      outcome of pregnancy.
AB  - BACKGROUND: In a previous hospital based study, we suggested that undiagnosed
      coeliac disease has a prevalence, among pregnant women, of 1:80, and is a cause
      of unfavourable outcome of pregnancy. AIMS: In order to confirm or dismiss this
      hypothesis, which has significant public health implications, we carried out a
      large population based study on a stratified sample from the whole Campania
      region. PATIENTS: During the period of the study, 5345 women were admitted to the
      OBS-GYN wards regional network: 5055 (95%) were enrolled in the study. METHODS:
      Antihuman IgA class antitissue transglutaminase (TGASE) antibodies were tested by
      an ELISA method. Endomysial antibodies (EMA) were investigated on thin sections
      of human cord blood by an immunofluorescence test. The HLA class II
      DQA1*0501/DQB1*02 and DQA1*0301/DQB1*0302 haplotypes were assessed using the
      Eurospital Eu-DQ kit. Duodenal biopsy was not considered feasible by the ethics
      committee for pregnant women near delivery. RESULTS: Fifty one of 5055 patients
      had confirmed positive results. We added to these 12 women with known coeliac
      disease, giving a prevalence rate for coeliac disease of 1:80 (exactly the value
      observed during the first study). Comparing the 51 TGASE positive with 4997
      negative women, we did not observe an excess risk of abortion, premature
      delivery, small birth weight, or intrauterine growth retardation. Anaemia was
      more frequent in cases than controls. CONCLUSIONS: Undiagnosed coeliac disease is
      frequent among pregnant women (>1%) but is not associated with an unfavourable
      outcome of pregnancy.

PMID- 14684591
TI  - Westernisation of gastrointestinal diseases in Asia.
AB  - Report on the Asia Pacific Congress of Gastroenterology Digestive Week,
      Singapore, 2003

PMID- 14684593
TI  - Should we screen adults with osteoporotic fractures for coeliac disease?

PMID- 14684594
TI  - Cyclooxygenase 2 selective inhibitor induced bowel stricture: a case report.

PMID- 14684595
TI  - Diet and colorectal cancer: fibre back on the menu?

PMID- 14684596
TI  - Mesalazine is safe for the treatment of IBD.

PMID- 14684597
TI  - Obesity as a risk factor for colorectal polyps in Japanese patients.

PMID- 14684598
TI  - Insulin-like growth factor-induced transcriptional activity of the skeletal alpha
      actin gene is regulated by signaling mechanisms linked to voltage-gated calcium
      channels during myoblast differentiation.
AB  - IGF-I activates signaling pathways that increase the expression of muscle
      specific genes in differentiating myoblasts. Induction of skeletal alpha-actin
      expression occurs during differentiation through unknown mechanisms. The purpose
      of this investigation was to examine the mechanisms that IGF-I uses to induce
      skeletal alpha-actin gene expression in C2C12 myoblasts. IGF-I increased skeletal
      alpha-actin promoter activity by 107% compared with the control condition. Ni(+)
      [T-type voltage-gated Ca(2+) channel (VGCC) inhibitor] reduced basal-induced
      activation of the skeletal alpha-actin promoter by approximately 84%, and
      nifedipine (L-type VGCC inhibitor) inhibited IGF-I-induced activation of the
      skeletal alpha-actin promoter by 29-48%. IGF-I failed to increase skeletal alpha
      actin promoter activity in differentiating dysgenic (lack functional L-type VGCC)
      myoblasts; 30 mm K(+) and 30 mm K(+)+IGF-I increased skeletal alpha-actin
      promoter activity by 162% and 76% compared with non-IGF-I or IGF-I-only
      conditions, respectively. IGF-I increased calcineurin activity, which was
      inhibited by cyclosporine A. Further, cyclosporine A inhibited K(+)+IGF-I-induced
      activation of the skeletal alpha-actin promoter. Constitutively active
      calcineurin increased skeletal alpha-actin promoter activity by 154% and rescued
      the nifedipine-induced inhibition of L-type VGCC but failed to rescue the Ni(+)
      inhibition of T-type VGCC. IGF-I-induced nuclear factor of activated T-cells
      transcriptional activity was not inhibited by nifedipine or Ni(+). IGF-I failed
      to increase serum response factor transcriptional activity; however, serum
      response factor activity was reduced in the presence of Ni(+). These data suggest
      that IGF-I-induced activation of the skeletal alpha-actin promoter is regulated
      by the L-type VGCC and calcineurin but independent of nuclear factor of activated
      T-cell transcriptional activity as C2C12 myoblasts differentiate into myotubes.

PMID- 14684599
TI  - Furin and prohormone convertase 1/3 are major convertases in the processing of
      mouse pro-growth hormone-releasing hormone.
AB  - We investigated the proteolytic processing of mouse pro-GHRH [84 amino acids
      (aa)] by furin, PC1/3, PC2, and PC5/6A. We created six point mutations in the N-
      and C-terminal cleavage sites, RXXR decreased and RXRXXR decreased, respectively.
      The following results were obtained after transient transfection/cotransfection
      and metabolic pulse-chase labeling studies in several neuroendocrine cells. 1)
      Furin was the most efficient convertase in cleaving the N-terminal RXXR/RXRR site
      to generate intermediate I, 12-84aa, whereas PC1/3 was the most potent in
      processing the C-terminal RXRXXR site to yield mature GHRH, 12-53aa. 2) Both
      PC1/3 and PC5/6A also processed the N-terminal site but less efficiently than
      furin. 3) PC2 was much weaker in cleaving the C-terminal site relative to PC1/3
      to generate mature GHRH. 4) The Q10R mutant was significantly more susceptible to
      furin cleavage at the N-terminal site than the wild-type pro-GHRH. And 5) the N-
      and C-terminal P1 Arg residues, R11 and R54, respectively, were essential for
      mature GHRH production. We also showed localization of the GHRH immunoreactive
      peptides in Golgi and secretory granules in neuroendocrine cells by an
      immunofluorescence assay. We conclude that the efficient production of mature
      GHRH from pro-GHRH is a stepwise process mediated predominantly by furin at the N
      terminal cleavage site followed by PC1/3 at the C terminus.

PMID- 14684600
TI  - A hypothalamic-testicular neural pathway is influenced by brain catecholamines,
      but not testicular blood flow.
AB  - We previously reported the existence of a descending multisynaptic, pituitary
      independent, neural pathway between the hypothalamus and the testes in the male
      rat. Stimulation of this pathway by the intracerebroventricular (icv) injection
      of IL-1beta or corticotropin-releasing factor blunts the testosterone (T)
      response to human chorionic gonadotropin (hCG). This response is mediated at
      least in part by catecholamine beta-adrenergic receptor activation. The present
      work was performed to further investigate the role of brain catecholamines and
      testicular blood flow in this pathway. The icv injection of 5 microl of 200 proof
      ethanol (EtOH; 86 micromol) did not result in detectable levels of the drug in
      the general circulation and did not induce neuronal damage, but rapidly blunted
      hCG-induced T release while not decreasing LH levels or altering testicular blood
      flow. EtOH significantly up-regulated transcripts of the immediate-early gene c
      fos in the paraventricular nucleus (PVN) of the hypothalamus. Lesions of the PVN
      blocked the inhibitory effect of IL-1beta on T, but only partially interfered
      with the influence of EtOH. PVN catecholamine turnover significantly increased
      after icv injection of IL-1beta, but not EtOH. Brain catecholamine depletion due
      to the neurotoxin 6-hydroxydopamine did not alter the ability of hCG to induce T
      release, but significantly reversed the inhibitory effect of icv EtOH or IL-1beta
      on this response. Collectively, these results indicate that icv-injected IL-1beta
      or EtOH blunts hCG-induced T secretion through a catecholamine-mediated mechanism
      that does not depend on either peripherally mediated effects or pituitary LH, and
      that the PVN plays a role in these effects.

PMID- 14684601
TI  - Lipopolysaccharide induces type 2 iodothyronine deiodinase in the mediobasal
      hypothalamus: implications for the nonthyroidal illness syndrome.
AB  - To determine whether the type 2 iodothyronine deiodinase (D2), the principal
      central nervous system enzyme converting T(4) to biologically active T(3), is
      regulated in tanycytes by immune activation, D2 activity was measured in the
      mediobasal hypothalamus (MBH) 4, 12, and 24 h after administration of bacterial
      lipopolysaccharide (LPS) and compared with D2 levels in the cortex and anterior
      pituitary of rats. In contrast to D2 activity in the cortex and anterior
      pituitary that showed a steady linear increase over 24 h, which was coincident
      with a decline in thyroid hormone and TSH levels, D2 activity peaked in the MBH
      12 h after LPS administration. By in situ hybridization, the increased D2 mRNA
      synthesis induced by LPS was specifically localized to tanycytes lining the third
      ventricle. In vitro assays in HC11 and HEK-293 cells demonstrated that the p65
      subunit of nuclear factor-kappaB markedly increased both rat and human D2 genes
      (dio2) as analyzed by promoter assays. No activation of human dio2 was observed
      when an 83-bp minimal promoter was used. We propose that LPS or LPS-induced
      cytokines directly induce D2 mRNA in tanycytes. The ensuing MBH-specific D2
      mediated local thyrotoxicosis may suppress the hypothalamus-pituitary-thyroid
      axis by local feedback inhibition of hypophysiotropic TRH and/or TSH and
      contribute to the mechanism of central hypothyroidism associated with infection.

PMID- 14684602
TI  - Estrogen replacement reverses the hepatic steatosis phenotype in the male
      aromatase knockout mouse.
AB  - The aromatase knockout (ArKO) mouse cannot synthesize endogenous estrogens due to
      a disruption to the Cyp19 gene. Previously we have shown both male and female
      ArKO mice have an age progressive obese phenotype and a sexually dimorphic
      disruption to hepatic cholesterol and triglyceride homeostasis. Only ArKO males
      have elevated hepatic triglyceride levels leading to hepatic steatosis partly due
      to an increase in expression of enzymes involved in de novo lipogenesis and
      transporters involved in fatty acid uptake. In this study ArKO males were treated
      with 17beta-estradiol (3 microg/ kg x d) at 18 wk old for 6 wk. Wild-type
      controls were not treated, and ArKO controls received vehicle oil injections.
      Estrogen replacement reverses the previously reported obese and fatty liver
      phenotypes; this was achieved by reductions in gonadal, visceral, and brown
      adipose tissue weights and significantly decreased hepatic triglyceride levels.
      Estrogen deficiency led to a significant up-regulation of hepatic fatty acid
      synthase expression, which was reduced with 17beta-estradiol replacement,
      although not quite reaching significance. Acetyl Coenzyme A carboxylase alpha
      mRNA expression showed no significant changes. Expression of transcripts encoding
      adipocyte differentiated regulatory protein, a fatty acid transporter, was
      significantly elevated in estrogen-deficient males, and 17beta-estradiol
      replacement significantly reduced these levels. Scavenger receptor class b type 1
      showed no significantly changes. This study reveals that the previously reported
      disruption to triglyceride homeostasis in estrogen-deficient males can be
      reversed with 17beta-estradiol treatment, indicating an important role for
      estrogen in maintaining triglyceride and fatty acid homeostasis in males.

PMID- 14684603
TI  - Photoinducible phase-specific light induction of Cry1 gene in the pars tuberalis
      of Japanese quail.
AB  - Prolactin (PRL) secretion is regulated by photoperiod in mammals and birds. In
      mammals, the pars tuberalis (PT) in the pituitary is involved in the regulation
      of photoperiodic regulation of PRL secretion. In birds, however, hypothalamic
      vasoactive intestinal peptide is implicated in PRL secretion, and physiological
      roles of the avian PT remain unknown. In the present study, we show that PRL
      secretion increases under long days and short days with a night interruptive
      schedule, both of which also cause gonadal growth in Japanese quail. We have also
      found Cry1 gene expression in the PT of Japanese quail. Cry1 expression was
      rhythmic under long and short photoperiods in the PT, and the peak was phase
      delayed under a lengthened photoperiod. Moreover, expression of Cry1 gene was
      induced by a light pulse but only when given during the photoinducible phase. In
      our previous study, we have shown rhythmic Per2 gene expression with a peak in
      the PT during the early day under various photoperiods. When taken together with
      the results from the present study, different phase relationships between Per2
      and Cry1 in the Japanese quail PT under different photoperiods may decode
      photoperiodic information and regulate photoperiodic PRL secretion in a manner
      similar to that of mammals.

PMID- 14684604
TI  - Trophoblast differentiation in embryoid bodies derived from human embryonic stem
      cells.
AB  - Trophoblast differentiation and early placental development are essential for the
      establishment of pregnancy, yet these critical events are not readily
      investigated in human pregnancy. We used embryoid bodies (EBs) prepared from
      human embryonic stem (hES) cells as an in vitro model of early human development.
      The levels of human chorionic gonadotropin (hCG), progesterone, and estradiol
      17beta in medium from hES cell-derived EBs grown in suspension culture for 1 wk
      were higher than unconditioned culture medium or medium from undifferentiated hES
      cells or spontaneously differentiated hES cell colonies. EBs were explanted into
      Matrigel (MG) "rafts" and cultured for up to 53 d. During the first 7-10 d of
      three-dimensional growth in MG, small protrusions appeared on the outer surface
      of EBs, some of which subsequently extended into multicellular outgrowths. The
      secretion of hCG, progesterone, and estradiol-17beta began to increase on
      approximately d 20 of MG culture and remained dramatically elevated over the next
      30 d. EBs maintained in suspension culture failed to demonstrate this elevation
      in hormone secretion. Suspension-cultured and MG-embedded EBs exhibited
      widespread expression of cytokeratins 7/8, demonstrating extensive epithelial
      differentiation as well as consistent hCG expression. We propose that hES cell
      derived EBs may be a useful model for investigation of human trophoblast
      differentiation and placental morphogenesis.

PMID- 14684605
TI  - Evidence of a role for follicle-stimulating hormone in controlling the rate of
      preantral follicle development in sheep.
AB  - Autografting ovarian cortex results in the loss of growing follicles and elevated
      gonadotropins. This paradigm was employed to examine the effect of gonadotropins
      on preantral follicle development in sheep. Ovarian tissue was recovered at 1, 2,
      3, and 4 months after grafting from ewes that were either hyper- (n = 12;
      untreated) or hypogonadotropic (n = 12; GnRH-agonist and estradiol implants).
      Compared with the Hypo group, Hyper ewes had higher (P < 0.001) gonadotropins,
      had greatly enlarged grafts, had reestablished a normal follicular hierarchy 2
      months earlier (P < 0.05), had higher (P < 0.05) levels of proliferating cell
      nuclear antigen expression in tertiary, preantral, and antral follicles, and had
      higher (P < 0.01) concentrations of inhibin A and estradiol. Compared with time
      zero controls, increases in the number of primary follicles and the rate of
      proliferation in primary and secondary follicles in both groups of autografts (P
      < 0.05) were also observed. In conclusion, the results of this experiment provide
      the first evidence that gonadotropins can affect the rate of development of
      preantral follicles in vivo in a large monovulatory species. Furthermore data are
      presented to support the existence of a gonadotropin-independent intraovarian
      feedback loop regulating both the rate of primordial follicle initiation and
      primary and secondary follicle development.

PMID- 14684606
TI  - Luteinizing hormone-induced connexin 43 down-regulation: inhibition of
      translation.
AB  - The coordinated function of the different compartments of the follicle, the
      oocyte and the somatic cumulus/granulosa cells, is enabled by the presence of a
      network of cell-to-cell communication generated by gap junctions. Connexin 43
      (Cx43) is the most abundant gap junction protein expressed by the ovarian
      follicle. The expression of Cx43 is subjected to the control of gonadotropins as
      follows: FSH up-regulates, whereas LH down-regulates its levels. The aim of this
      study was to explore the mechanism by which LH reduces the levels of Cx43 and to
      identify the signal transduction pathway involved in this process. The effect of
      LH was studied in vitro using isolated intact ovarian follicles. The possible
      mediators of LH-induced Cx43 down-regulation were examined by incubating the
      follicles with LH in the presence or absence of inhibitors of protein kinase A
      (PKA) and of MAPK signaling pathways. Our experiments revealed a 3-h half-life of
      Cx43 in both control and LH-treated follicles, suggesting that LH did not affect
      the rate of Cx43 degradation. We further demonstrated that the level of Cx43 mRNA
      was not significantly influenced by this gonadotropin. However, upon LH
      administration, [(35)S]methionine incorporation into Cx43 protein was remarkably
      reduced. The LH-induced arrest of Cx43 synthesis was counteracted by inhibitors
      of both the PKA and the MAPK cascades. We show herein that LH inhibits Cx43
      expression by reducing its rate of translation and that this effect is mediated
      by both PKA and MAPK.

PMID- 14684607
TI  - Thyroid hormone resistance in the heart: role of the thyroid hormone receptor
      beta isoform.
AB  - Several cardiac genes possess thyroid hormone (TH) response elements regulated by
      TH receptors. Mutation in TR-beta gene causes the human syndrome of resistance to
      TH, which is characterized by elevated serum concentration of T(4) and T(3) and
      variable degrees of insensitivity to TH. It is unclear, however, whether a mutant
      TR-beta could function as a dominant negative in the heart when expressed from
      the endogenous locus. A well-described resistance to TH (Delta337T) was either
      introduced into germline of mice (KI-mut) or expressed as a transgene in the
      heart using a cardiac-specific promoter (KS-mut). Mice were studied at baseline,
      after 5-propyl-2-thiouracil (PTU) or after PTU and T(3) treatment (PTU + T(3)).
      PTU + T(3) treatment significantly increased left ventricular mass in all groups
      compared with baseline measurements, although the increase in left ventricular
      mass was significantly less in KI-mut animals. Baseline heart rates (HRs) were
      similar in wild-type (WT) and KI-mut but were lower in KS-mut animals. After TH
      deprivation (PTU), HR decreased in WT and KI-mut animals; similarly, HR increased
      in WT and KI-mut after PTU + T(3). In contrast, HR in KS-mut animals did not
      change after either treatment. Except for cardiac hypertrophy, the presence of a
      germline TR-beta mutation had surprisingly little effect on cardiac function.

PMID- 14684608
TI  - Identification and characterization of two parathyroid hormone-like molecules in
      zebrafish.
AB  - Zebrafish (Danio rerio) have receptors homologous to the human PTH (hPTH)/PTHrP
      receptor (PTH1R) and PTH-2 receptor (PTH2R) and an additional receptor (PTH3R)
      with high homology to the PTH1R. To find natural ligands for zPTH1R and zPTH3R,
      we searched the zebrafish genomic database and discovered two distinct regions
      that, when translated (zPTH1 and zPTH2), showed high homology to hPTH. Isolation
      of cDNAs and determination of the intron/exon boundaries revealed genomic
      structures which were similar to known PTHs. Peptides consisting of the first 34
      amino acids after the pre- and prosequences of the zebrafish PTHs (zPTHs) were
      synthesized and were shown to be fully active at the hPTH1R. zPTH2(1-34) was,
      however, approximately 30-fold less potent at the zPTH1R than hPTH(1-34),
      hPTHrP(1-36), and zPTH1(1-34). When tested with zPTH3R, zPTH1(1-34) and hPTHrP(1
      36) showed similar potencies, whereas the potency of zPTH2(1-34) was moderately
      (3-fold) reduced. To determine whether other fishes have multiple PTHs, we
      searched the genomic database of the Japanese pufferfish (Takifugu rubripes) and
      identified zPTH1 and zPTH2 homologs. Phylogenetic analysis showed that PTHs from
      zebrafish and pufferfish are more closely related to each other than to known
      mammalian PTH homologs or to PTHrP and tuberoinfundibular peptide of 39 residues.
      This is consistent with evolution of two teleost PTH-like peptides occurring
      after the evolutionary divergence between fishes and mammals. Overall, the PTH
      system appears more complex in fishes than in mammals, providing evidence of
      continued evolution in nontetrapod species. The availability of multiple forms of
      fish PTH and their receptors provide additional tools for PTH ligand/receptor
      structure-function studies.

PMID- 14684609
TI  - Aromatase-knockout mouse carrying an estrogen-inducible enhanced green
      fluorescent protein gene facilitates detection of estrogen actions in vivo.
AB  - Aromatase is an enzyme that converts androgen to estrogen in the gonads and also
      at extragonadal sites, including the brain. In this study we developed a
      transgenic mouse that carries an enhanced green fluorescent protein (EGFP) gene
      inducible by estrogen through an estrogen response element to facilitate
      detection of estrogen actions in vivo. The expression of EGFP in aromatase
      deficient (Ar(-/-)) female mice was significantly suppressed at the pituitary
      gland, ovary, uterus, and gonadal fat pad and was induced by dietary 17beta
      estradiol to wild-type (Ar(+/+)) levels or higher. These results demonstrate that
      the expression of the EGFP gene is tissue selective and estrogen dependent in
      vivo. Employing this transgenic mouse, we examined whether estrogen synthesis in
      the extragonadal sites is necessary for reproduction in female mice. When ovaries
      of Ar(-/-) mice were replaced with Ar(+/+) ovaries, a significant induction of
      EGFP expression in the pituitary gland and uterus was observed. Histological
      examinations showed the presence of antral follicles in the replaced ovaries,
      indicating that the transplants are functional in Ar(-/-) mice. After crossing
      with males, three of 10 Ar(-/-)females with Ar(+/+) ovaries became pregnant and
      fed their pups. Collectively, these observations indicate that estrogen synthesis
      in the ovary is sufficient for supporting female reproduction, and that
      infertility of Ar(-/-) females is primarily due to a defect in estrogen synthesis
      in the ovary.

PMID- 14684610
TI  - Identification and characterization of an androgen-responsive gene encoding an
      aci-reductone dioxygenase-like protein in the rat prostate.
AB  - The ALP1 [aci-reductone dioxygenase (ARD)-like protein 1] gene was identified in
      a comprehensive cDNA subtraction aimed at identifying genes regulated by
      androgens in the rat ventral prostate. ALP1 is homologous to the ARD/ARD' that
      were discovered in Klebsiella pneumoniae as enzymes that have the same
      polypeptide sequence and differ only in their metal content. This family of
      proteins is evolutionarily conserved from bacteria to humans and is involved in
      the methionine salvage pathway. Northern and Western blot confirmed the
      regulation of ALP1 by androgens in the rat ventral prostate. ALP1 mRNA is
      expressed in a variety of tissues; however, its regulation by androgens was
      specific to the prostate. ALP1 is expressed by the glandular epithelial cells of
      the rat prostate, with little or no expression in the stromal cells. ALP1 is down
      regulated in the different rat Dunning tumor cell lines compared with the normal
      or castrated rat prostate. Expression studies showed that ALP1 overexpression is
      not tolerated by AT6.1 cells. Further studies demonstrated that ALP1 is also down
      regulated in the human prostate cancer cell lines LNCaP, PC3, and DU145, and
      overexpression induces cell death in these cells. Taken together, our
      observations suggest that ALP1 may have an important role in androgen regulated
      prostate homeostasis as well as in prostate cancer progression by regulating cell
      death of prostate cancer cells.

PMID- 14684611
TI  - Regulation of cyclooxygenase expression by vasopressin in rat renal medulla.
AB  - The antagonism between prostaglandin and vasopressin represents a classic
      negative feedback loop. It is not clear whether cyclooxygenase (COX)-2 and/or COX
      1 expression is involved in elevated prostaglandin production stimulated by
      vasopressin in vivo. In the present study, we explored vasopressin regulation of
      medullary COX-2 and COX-1 expression acutely and chronically in rats. Medullary
      COX-1 expression was moderately lower and COX-2 expression was significantly
      lower in adult male Brattleboro rats than age-matched Long-Evans controls.
      Chronic treatment of Brattleboro rats with vasopressin for 1 wk led to a decrease
      in urine volume and a moderate increase in medullary COX-1; in contrast,
      medullary COX-2 expression was almost undetectable in untreated rats but was
      dramatically up-regulated with vasopressin treatment and was accompanied by
      increased urinary prostaglandin E(2) excretion. Further investigation revealed
      that both V1 and V2 receptors were involved in chronic medullary COX-1 and COX-2
      up-regulation. Acute treatment with specific V1 or V2 receptor agonists resulted
      in specific increases in medullary COX-2, which was prevented by furosemide.
      Vasopressin did not affect COX-2 expression in cultured renomedullary
      interstitial cells. These data demonstrate that vasopressin stimulates medullary
      COX-2 expression through activation of both V1 and V2 receptors, and this
      stimulation is indirect and probably involves increased medullary electrolyte
      tonicity.

PMID- 14684612
TI  - Cellular and molecular mechanisms of adipose tissue plasticity in muscle insulin
      receptor knockout mice.
AB  - White adipose tissue (WAT) plays a critical role in the development of insulin
      resistance via secretion of free fatty acids (FFA) and adipocytokines. Muscle
      specific insulin receptor knockout (MIRKO) mice do not develop insulin resistance
      or diabetes under physiological conditions despite a marked increase in adiposity
      and plasma FFA. On the contrary, WAT of MIRKO is sensitized to insulin action
      during a euglycemic clamp, and WAT glucose utilization is dramatically increased.
      To get insight into the potential antidiabetic role of MIRKO adiposity, we have
      studied insulin action in WAT during a euglycemic, hyperinsulinemic clamp, and we
      have characterized the morphology and biology of WAT. During the clamp, there is
      no alteration in the expression or activation in the insulin signaling molecules
      involved in glucose transport through the phosphoinositide 3-kinase/Akt and
      CAP/Cbl pathways in WAT from MIRKO. The 53% increase in WAT mass results from a
      48% increase in adipocyte number (P < 0.05) without alteration in cell size and
      contemporary to a 300% increase in mRNA levels of the adipogenic transcription
      factor CCAAT enhancer binding protein-alpha (C/EBP-alpha) (P < 0.05). There is a
      39.5% increase in serum adiponectin (P < 0.01) without modification in serum
      leptin, resistin, and TNF-alpha. In conclusion, the MIRKO mouse displays muscle
      insulin resistance, visceral obesity, and dyslipidemia but does not develop
      hyperinsulinemia or diabetes. There is an accelerated differentiation of small
      insulin sensitive adipocytes, an increased secretion of the insulin sensitizer
      adiponectin, and maintenance of leptin sensitivity. The MIRKO mouse confirms the
      importance of WAT plasticity in the maintenance of whole body insulin sensitivity
      and represents an interesting model to search for new secreted molecules that
      positively alter adipose tissue biology.

PMID- 14684613
TI  - Female-predominant expression of fatty acid translocase/CD36 in rat and human
      liver.
AB  - The aim of this study was to identify genes for hepatic fuel metabolism with a
      gender-differentiated expression and to determine which of these that might be
      regulated by the female-specific secretion of GH. Effects of gender and
      continuous infusion of GH to male rats were studied in the liver using cDNA
      microarrays representing 3200 genes. Sixty-nine transcripts displayed higher
      expression levels in females, and 177 displayed higher expression in males. The
      portion of GH-regulated genes was the same (30%) within the two groups of gender
      specific genes. The male liver had a higher expression of genes involved in fuel
      metabolism, indicating that male rats might have a greater capacity for high
      metabolic turnover, compared with females. Most notable among the female
      predominant transcripts was fatty acid translocase/CD36, with 18-fold higher mRNA
      levels in the female liver and 4-fold higher mRNA levels in males treated with
      GH, compared with untreated males. This gender-differentiated expression was
      confirmed at mRNA and protein levels in the rat and at the mRNA level in human
      livers. Although purely speculative, it is possible that higher levels of fatty
      acid translocase/CD36 in human female liver might contribute to the sexually
      dimorphic development of diseases resulting from or characterized by disturbances
      in lipid metabolism, such as arteriosclerosis, hyperlipidemia, and insulin
      resistance.

PMID- 14684614
TI  - CCAAT/enhancer binding protein homologous protein (DDIT3) induces osteoblastic
      cell differentiation.
AB  - CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP/DDIT3), a member
      of the C/EBP family of transcription factors, plays a role in cell survival and
      differentiation. CHOP/DDIT3 binds to C/EBPs to form heterodimers that do not bind
      to consensus Cebp sequences, acting as a dominant-negative inhibitor. CHOP/DDIT3
      blocks adipogenesis, and we postulated it could induce osteoblastogenesis. We
      investigated the effects of constitutive CHOP/DDIT3 overexpression in murine ST-2
      stromal cells transduced with retroviral vectors. ST-2 cells differentiated
      toward osteoblasts, and CHOP/DDIT3 accelerated and enhanced the appearance of
      mineralized nodules, and the expression of osteocalcin and alkaline phosphatase
      mRNAs, particularly in the presence of bone morphogenetic protein-2. CHOP/DDIT3
      overexpression opposed adipogenesis, and did not cause substantial changes in
      cell number. CHOP/DDIT3 overexpression did not modify C/EBPalpha or -beta mRNA
      levels but decreased C/EBPdelta after 24 d of culture. Electrophoretic mobility
      shift and supershift assays demonstrated that overexpression of CHOP/DDIT3
      decreased the binding of C/EBPs to their consensus sequence by interacting with
      C/EBPalpha and -beta, confirming its dominant-negative role. In addition,
      CHOP/DDIT3 enhanced bone morphogenetic protein-2/Smad signaling. In conclusion,
      CHOP/DDIT3 enhances osteoblastic differentiation of stromal cells, in part by
      interacting with C/EBPalpha and -beta and also by enhancing Smad signaling.

PMID- 14684615
TI  - Activation of the hexosamine signaling pathway in adipose tissue results in
      decreased serum adiponectin and skeletal muscle insulin resistance.
AB  - Overexpression of the rate-limiting enzyme for hexosamine synthesis
      (glutamine:fructose-6-phosphate amidotransferase) in muscle and adipose tissue of
      transgenic mice was previously shown to result in insulin resistance and
      hyperleptinemia. Explanted muscle from transgenic mice was not insulin resistant
      in vitro, suggesting that muscle insulin resistance could be mediated by soluble
      factors from fat tissue. To dissect the relative contributions of muscle and fat
      to hexosamine-induced insulin resistance, we overexpressed glutamine:fructose-6
      phosphate amidotransferase 2.5-fold, specifically in fat under control of the aP2
      promoter. Fasting glucose, insulin, and triglycerides were unchanged in the
      transgenic mice; leptin and beta-hydroxybutyrate levels were 91% and 29% higher,
      respectively. Fasted transgenic mice have mild glucose intolerance and skeletal
      muscle insulin resistance in vivo. In fasting transgenic mice, glucose disposal
      rates with hyperinsulinemia were decreased 27% in females and 10% in males.
      Uptake of 2-deoxy-D-glucose into muscle was diminished by 45% in female and 21%
      in male transgenics. Serum adiponectin was also lower in the fasted transgenics,
      by 37% in females and 22% in males. TNF alpha and resistin mRNA levels in adipose
      tissue were not altered in the fasted transgenics; levels of mRNA for leptin were
      increased and peroxisome proliferator-activated receptor gamma decreased. To
      further explore the relationship between adiponectin and insulin sensitivity, we
      examined mice that have been refed for 6 h after a 24-h fast. Refeeding wild-type
      mice resulted in decreased serum adiponectin and increased leptin. In transgenic
      mice, however, the regulation of these hormones by refeeding was lost for
      adiponectin and diminished for leptin. Refed transgenic female and male mice no
      longer exhibited decreased serum adiponectin in the refed state, and they were no
      longer insulin resistant as by lower or unchanged insulin and glucose levels. We
      conclude that increased hexosamine levels in fat, mimicking excess nutrient
      delivery, are sufficient to cause insulin resistance in skeletal muscle. Changes
      in serum adiponectin correlate with the insulin resistance of the transgenic
      animals.

PMID- 14684616
TI  - Dihydrotestosterone promotes vascular cell adhesion molecule-1 expression in male
      human endothelial cells via a nuclear factor-kappaB-dependent pathway.
AB  - There exists a striking gender difference in atherosclerotic vascular disease.
      For decades, estrogen was considered atheroprotective; however, an alternative is
      that androgen exposure in early life may predispose men to earlier
      atherosclerosis. We recently demonstrated that the potent androgen,
      dihydrotestosterone (DHT), enhanced the binding of monocytes to the endothelium,
      a key early event in atherosclerosis, via increased expression of vascular cell
      adhesion molecule-1 (VCAM-1). We now show that DHT mediates its effects on VCAM-1
      expression at the promoter level through a novel androgen receptor (AR)/nuclear
      factor-kappaB (NF-kappaB) mechanism. Human umbilical vein endothelial cells were
      exposed to 4-400 nm DHT. DHT increased VCAM-1 mRNA in a dose- and time-dependent
      manner. The DHT effect could be blocked by the AR antagonist, hydroxyflutamide.
      DHT increased VCAM-1 promoter activity via NF-kappaB activation without affecting
      VCAM-1 mRNA stability. Using 5' deletion analysis, it was determined that the NF
      kappaB sites within the VCAM-1 promoter region were responsible for the DHT
      mediated increase in VCAM-1 expression; however, coimmunoprecipitation studies
      suggested there is no direct interaction between AR and NF-kappaB. Instead, DHT
      treatment decreased the level of the NF-kappaB inhibitory protein. DHT did not
      affect VCAM-1 protein expression and monocyte adhesion when female endothelial
      cells were tested. AR expression was higher in male, relative to female,
      endothelial cells, associated with increased VCAM-1 levels. These findings
      highlight a novel AR/NF-kappaB mediated mechanism for VCAM-1 expression and
      monocyte adhesion operating in male endothelial cells that may represent an
      important unrecognized mechanism for the male predisposition to atherosclerosis.

PMID- 14684617
TI  - Estradiol represses prolactin-induced expression of Na+/taurocholate
      cotransporting polypeptide in liver cells through estrogen receptor-alpha and
      signal transducers and activators of transcription 5a.
AB  - Na(+)/taurocholate cotransporting polypeptide (ntcp) mediates the uptake of bile
      salts from plasma across the basolateral domain of the hepatocyte. We have
      demonstrated that ntcp expression can be induced by prolactin (PRL) and placental
      lactogen via the PRL receptor and signal transducers and activators of
      transcription (Stat)5a pathway. However, elevated levels of placental lactogen do
      not increase the expression of ntcp in pregnant rats. Because plasma estradiol
      (E(2)) levels are also elevated in pregnancy, we investigated the inhibitory
      effects of E(2) on PRL-induced ntcp activation. E(2) treatment inhibited the PRL
      induced increase in liver ntcp mRNA to the same levels as in rats treated with
      E(2) alone. Estrogen receptor-alpha (ERalpha) mRNA and protein expression in
      liver were increased 2.6-fold and 2.2-fold, respectively, in pregnancy relative
      to controls. In HepG2 cells, E(2) repressed PRL-induced ntcp reporter gene
      expression in a dose-dependent manner in the presence of cotransfected ERalpha.
      The ERalpha antagonist ICI 182,780 reversed E(2)-induced repression, indicating
      specificity of inhibition by E(2). Overexpression of coactivator p300 did not
      reverse the inhibitory effects of E(2) and ERalpha. Western and gel shift
      analysis revealed that E(2)-bound ERalpha decreased the tyrosine phosphorylation
      and DNA-binding activity of Stat5a, indicating that the inhibitory effect of E(2)
      was mediated, at least in part, by interfering with PRL-mediated signal
      transduction. The present studies demonstrate the physiological significance of
      cross-talk between ERalpha and Stat5a in liver, in which both proteins are
      expressed. These data also establish a novel mechanism by which expression of
      ntcp, an important hepatic bile acid transporter, can be regulated by multiple
      hormones.

PMID- 14684618
TI  - Improved accuracy of detection of nasopharyngeal carcinoma by combined
      application of circulating Epstein-Barr virus DNA and anti-Epstein-Barr viral
      capsid antigen IgA antibody.
AB  - BACKGROUND: Circulating Epstein-Barr viral (EBV) DNA and anti-EBV capsid antigen
      IgA (IgA VCA) represent two of the most sensitive peripheral blood markers of
      nasopharyngeal carcinoma (NPC), but direct comparative studies of these two
      markers are lacking. METHODS: The sensitivities and specificities of IgA-VCA and
      EBV DNA for diagnosis of NPC were determined in 139 new cases of NPC and 178
      healthy individuals, respectively. EBV DNA was also assessed in 36 healthy family
      members identified as having false-positive IgA-VCA results at a screening
      clinic. EBV DNA was measured by a real-time quantitative PCR assay with a
      detection limit of 60 copies/mL. IgA-VCA was measured by semiquantitative
      indirect immunofluorescent method; a titer > or =1/10 was taken as positive.
      RESULTS: The sensitivities of EBV DNA and IgA-VCA for diagnosis of NPC were 95%
      (95% confidence interval, 91-98%) and 81% (73-87%), respectively. The combined
      marker panel had an overall sensitivity (positive result by either marker) of
      99%. The concentrations of both markers showed dependence on cancer stage. The
      specificities of EBV DNA and IgA-VCA were 98% (96-99%) and 96% (91-98%),
      respectively. Among 36 healthy family members with false-positive IgA-VCA
      results, three-fourths had undetectable EBV DNA, whereas the others had increased
      EBV DNA concentrations that were significantly lower than in NPC patients.
      CONCLUSIONS: For diagnosis of NPC, EBV DNA identifies almost all false-negative
      IgA-VCA cases and gives a 99% diagnostic sensitivity when combined with IgA-VCA.
      In the screening setting, EBV DNA identifies three-fourths of false-positive IgA
      VCA cases. The selective application of EBV DNA in an IgA-VCA-based screening
      protocol could improve screening accuracy with only moderate increases in cost.

PMID- 14684619
TI  - High-throughput mutation detection method to scan BRCA1 and BRCA2 based on
      heteroduplex analysis by capillary array electrophoresis.
AB  - BACKGROUND: Scanning for mutations in BRCA1 and BRCA2 in a large number of
      samples is hampered by the large sizes of these genes and the scattering of
      mutations throughout their coding sequences. Automated capillary electrophoresis
      has been shown to be a powerful system to detect mutations by either single
      strand conformation polymorphism or heteroduplex analysis (HA). METHODS: We
      investigated the adaptation of gel-based HA of BRCA1 and BRCA2 to a fluorescent
      multicapillary platform to increase the throughput of this technique. We combined
      multiplex PCR, three different fluorescent labels, and HA in a 16-capillary DNA
      sequencer and tested 57 DNA sequence variants (11 insertions/deletions and 46
      single-nucleotide changes) of BRCA1 and BRCA2. RESULTS: We detected all 57 DNA
      changes in a blinded assay, and 2 additional single-nucleotide substitutions
      (1186 A>G of BRCA1 and 3624 A>G of BRCA2), previously unresolved by conformation
      sensitive gel electrophoresis. Furthermore, different DNA changes in the same PCR
      fragment could be distinguished by their peak patterns. CONCLUSIONS: Capillary
      based HA is a fast, efficient, and sensitive method that considerably reduces the
      amount of "hands-on" time for each sample. By this approach, the entire coding
      regions of BRCA1 and BRCA2 from two breast cancer patients can be scanned in a
      single run of 90 min.

PMID- 14684620
TI  - Factors behind the increase in cardiovascular mortality in Russia: apolipoprotein
      AI and B distribution in the Arkhangelsk study 2000.
AB  - BACKGROUND: Cardiovascular mortality is markedly higher in Russia than in Western
      Europe and the US. Little is known about indicators of atherosclerotic risk in
      the Russian population. To our knowledge, this is the first study of
      apolipoprotein (apo) AI and B in Russia based on the WHO-IFCC standard. METHODS:
      We measured apo AI and B by immunoturbidimetric assay in 3694 men and women from
      Arkhangelsk, Russia, in 1999-2000. RESULTS: The age-related distribution of apo B
      was similar to that in other countries, whereas the apo AI profile was different.
      For men > or = 20 years, apo AI was considerably higher than in studies from
      other countries. Women had also relatively high apo AI concentrations, although
      the difference was not as pronounced as in men. The apo AI concentration was
      positively associated with age and lifestyle variables such as alcohol
      consumption and physical activity, and negatively associated with body mass index
      and self-reported myocardial infarction. gamma-Glutamyltransferase was positively
      associated with apo AI in both sexes. CONCLUSIONS: The apparently favorable
      apolipoprotein profiles contrast with official death statistics indicating high
      cardiovascular mortality in Russia. High apo AI might indicate excessive alcohol
      consumption.

PMID- 14684621
TI  - Detection of human polyomaviruses in urine from bone marrow transplant patients:
      comparison of electron microscopy with PCR.
AB  - BACKGROUND: We studied electron microscopy (EM) as an appropriate test system for
      the detection of polyomavirus in urine samples from bone marrow transplant
      patients. METHODS: We evaluated direct EM, ultracentrifugation (UC) before EM,
      and solid-phase immuno-EM (SPIEM). The diagnostic accuracy of EM was studied by
      comparison with a real-time PCR assay on 531 clinical samples. RESULTS: The
      detection rate of EM was increased by UC and SPIEM. On 531 clinical urine
      samples, the diagnostic sensitivity of EM was 47% (70 of 149) with a specificity
      of 100%. We observed a linear relationship between viral genome concentration and
      the proportion of urine samples positive by EM, with a 50% probability for a
      positive EM result for urine samples with a polyomavirus concentration of 10(6)
      genome-equivalents (GE)/mL; the probability of a positive EM result was 0% for
      urine samples with <10(3) GE/mL and 100% for urine samples containing 10(9)
      GE/mL. CONCLUSIONS: UC/EM is rapid and highly specific for polyomavirus in urine.
      Unlike real-time PCR, EM has low sensitivity and cannot quantify the viral load.

PMID- 14684622
TI  - Effect of a controlled feedback intervention on laboratory test ordering by
      community physicians.
AB  - BACKGROUND: Most studies of interventions to reduce laboratory test utilization
      have occurred in academic hospital settings, used historical controls, or have
      had short post intervention follow-up. Interventions with the greatest impact use
      multiple approaches, are repeated regularly, include comparisons with physician
      peers, and have a personal approach. We determined whether laboratory test
      utilization by community physicians could be reduced by a multifaceted program of
      education and feedback. METHODS: We identified 200 physicians who ordered the
      largest number of common laboratory tests during 1 year in a nonhospital,
      commercial community (reference) laboratory. They were assigned to intervention
      and control groups (100 each). Intervention physicians were visited individually
      up to three times by laboratory representatives over a 2-year period. At each
      visit, educational material and the physician's personal laboratory test
      utilization data were presented and discussed briefly in general terms, with the
      latter compared with utilization data for the physician's peers. Overall test
      utilization rates 1 year before, during, and 2 years after the intervention were
      measured using population-based databases. Time-series analysis was used to
      determine the effect of the intervention on laboratory test utilization. RESULTS:
      The two groups began with similar test utilization: control group, 4.06 x 10(6)
      tests in 1.48 x 10(6) visits (2.73 tests/visit); intervention group, 3.90 x 10(6)
      tests in 1.41 x 10(6) visits (2.77 tests/visit). During the 2-year intervention,
      intention-to-treat analysis showed that utilization decreased significantly in
      the intervention group compared with the controls [relative reduction of 7.9% (P
      <0.0001); absolute reduction of 0.22 tests/visit (95% confidence interval, 0.20
      0.24)]. This difference persisted until the end of study observation, or more
      than 2 years after the intervention ended. CONCLUSION: A multifaceted education
      and feedback strategy can significantly and persistently decrease laboratory
      utilization by practicing community physicians.

PMID- 14684623
TI  - Technical and clinical characterization of the Bio-PTH (1-84)
      immunochemiluminometric assay and comparison with a second-generation assay for
      parathyroid hormone.
AB  - BACKGROUND: The Bio-Intact parathyroid hormone (1-84) assay (Bio-PTH), a newly
      developed two-site immunochemiluminometric assay, measures exclusively PTH (1-84)
      in contrast to second-generation "intact PTH" (I-PTH) assays. We investigated the
      technical performance and clinical significance of this new assay. METHODS: PTH
      was measured simultaneously by the Bio-PTH assay and Allegro intact PTH IRMA in
      sera from Japanese patients with calcium disorders. RESULTS: Measured Bio-PTH in
      serum was unaffected by six freeze-thaw cycles and was stable at 4 degrees C for
      7 days and during storage at -20 or -80 degrees C over 28 days. The calibration
      curve was linear to 1800 ng/L. The detection limit was 3.9 ng/L. The intra- and
      interassay imprecision was <2.8% and 3.5%, respectively, for analyte
      concentrations spanning the range of the calibration curve. Bio-PTH was
      unaffected by a 1000-fold excess of PTH (7-84), although I-PTH reacted equally
      with PTH (7-84) and PTH (1-84). Bio-PTH was correlated with I-PTH in healthy
      individuals (r = 0.953; P <0.0001; n = 26) and in the full population without
      renal dysfunction (r = 0.994; P <0.0001; n = 62). In 72 volunteers, mean (SD) Bio
      PTH was 22.2 (7.1) ng/L, or 62% of the mean I-PTH [36.1 (22.3) ng/L]. This ratio
      was 51% in hemodialysis patients (n = 177). Mean Bio-PTH was high in patients
      with primary hyperparathyroidism [121 (85) ng/L; n = 18] and hemodialysis
      patients [102 (104) ng/L; n = 177], low in idiopathic hypoparathyroidism [5.5
      (2.8) ng/L; n = 4], and within 2 SD of the mean for healthy controls in Paget
      disease of the bone [34 (15) ng/L; n = 9] and bone metastasis [24 (12) ng/L; n =
      8]. CONCLUSION: The Bio-PTH assay is sensitive and precise and produces expected
      results for patients with the studied disorders of calcium metabolism.

PMID- 14684624
TI  - Quantification of free sialic acid in urine by HPLC-electrospray tandem mass
      spectrometry: a tool for the diagnosis of sialic acid storage disease.
AB  - BACKGROUND: Sialic acid storage diseases (SSDs) are severe autosomal recessive
      neurodegenerative disorders caused by a transport defect across the lysosomal
      membrane, which leads to accumulation of sialic acid in tissues, fibroblasts, and
      urine. Defective free sialic acid transport can be established by quantification
      of free sialic acid in urine. METHODS: Urine sample size was adjusted to the
      equivalent of 100 nmol of creatinine. After addition of 2-keto-3-deoxy-d-glycero
      d-galactonononic acid as internal standard, samples were diluted with water to an
      end volume of 250 microL. We used 10 microL for HPLC-tandem mass spectrometric
      analysis in the negative electrospray ionization mode, monitoring transitions m/z
      308.3-->m/z 86.9 (sialic acid) and m/z 267.2-->m/z 86.9 (internal standard). The
      overall method was validated and studied for ion suppression, interfering
      compounds, and pH effects. Samples from controls (n = 72) and SSD patients (n =
      3) were analyzed. RESULTS: The limit of detection was 3 micromol/L. Intraassay
      imprecision (CV; n = 10) was 6%, 3%, and 2% at 30, 130, and 1000 mmol/mol
      creatinine, respectively; corresponding interassay CV (n = 10) were 5%, 5%, and
      2%. Recovery was 109% (100-1000 mmol/mol creatinine). The mean (SD) [range]
      excretion rates (mmol/mol creatinine) were 31.3 (16.6) [0.7-56.9] at 0-1 year (n
      = 20), 21.2 (9.8) [6.3-38.3] at 1-3 years (n = 15), 14.4 (8.2) [1.7-32.9] at 3-10
      years (n = 25), and 4.6 (2.6) [0-9.8] above age 10 years (n = 12). SSD patients
      1.2, 3.9, and 12 years of age had concentrations of 111.5, 54.2, and 36.1
      mmol/mol creatinine, respectively. CONCLUSIONS: The HPLC-tandem MS method for
      free sialic acid in urine is more rapid, accurate, sensitive, selective, and
      robust than earlier methods and may serve as a candidate reference method for
      free sialic acid in diagnosis of SSD.

PMID- 14684625
TI  - Development of proximal coronary arteries in quail embryonic heart: multiple
      capillaries penetrating the aortic sinus fuse to form main coronary trunk.
AB  - Studies have shown that the proximal coronary artery (PCA) develops via
      endothelial ingrowth from the peritruncal ring (PR) of the coronary vasculature.
      However, the details of PCA formation remain unclear. We examined the development
      of PCAs in quail embryonic hearts from 5 to 9 days of incubation (embryonic day
      [ED]) using double-immunostaining for QH1 (quail endothelial marker) and smooth
      muscle alpha-actin. At 6 to 7 ED, several QH1-positive endothelial strands from
      the PR penetrated the facing sinuses, and in some embryos, several endothelial
      strands penetrated the posterior (noncoronary) sinus. At 7 to 8 ED, the
      endothelial strands penetrating the facing sinuses seemed to fuse, forming a
      proximal coronary stem that was demarcated from the aortic wall by the nascent
      smooth muscle layer of the coronary artery. By 9 ED, two coronary stems were
      completely formed, and the endothelial strands previously penetrating the
      noncoronary sinus had disappeared. Confocal microscopy at 6 ED revealed
      discontinuous QH1-positive endothelial progenitors in the aortic wall at sites
      where the endothelial strands would later develop. Observations demonstrate that
      during the formation of the PCA, endothelial strands from the PR penetrate the
      facing sinuses and then fuse, whereas those strands penetrating the noncoronary
      sinus disappear. Thereafter, the coronary artery tunica media demarcates the
      definitive PCA from the aortic media.

PMID- 14684626
TI  - Superoxide is involved in the central nervous system activation and
      sympathoexcitation of myocardial infarction-induced heart failure.
AB  - Increased angiotensin II signaling in the brain has been shown to play a critical
      role in the excessive sympathoexcitation and development of heart failure (HF)
      after myocardial infarction (MI). We have recently demonstrated that reactive
      oxygen species mediate the actions of angiotensin II in the brain. In this study,
      we tested the hypothesis that increased redox signaling in central cardiovascular
      control regions is a key mechanism in the neurocardiovascular dysregulation that
      follows MI. Ligation of the left coronary artery induced a large MI and
      subsequent HF in adult C57BL/6 mice, as demonstrated by cardiac hypertrophy,
      hydrothorax, and ascites. Immunohistochemical analysis of Fos, a marker of
      neuronal activation, revealed a significant increase in the number of Fos
      positive neurons in the paraventricular nucleus and supraoptic nucleus at 2 and 4
      weeks after MI compared with sham mice. Intracerebroventricular injection of an
      adenoviral vector encoding superoxide dismutase (Ad-Cu/ZnSOD) caused a
      significant decrease in the number of Fos-positive neurons in the paraventricular
      nucleus and supraoptic nucleus at 2 weeks after MI compared with mice receiving
      either saline or a control vector (Ad-LacZ). There was also a diminished role of
      sympathetic drive in post-MI mice treated centrally with Ad-Cu/ZnSOD, as
      demonstrated by significantly attenuated falls in heart rate and mean arterial
      pressure to the ganglionic blocker hexamethonium and decreased urinary
      norepinephrine levels in these mice compared with Ad-LacZ-treated MI mice. These
      results suggest that superoxide plays a key role in the central activation and
      sympathetic hyperactivity after MI in mice and that oxygen radicals in the brain
      may be important new targets for therapeutic treatment of heart failure.

PMID- 14684627
TI  - Heparan sulfate proteoglycans function as receptors for fibroblast growth factor
      2 activation of extracellular signal-regulated kinases 1 and 2.
AB  - Fibroblast growth factor-2 (FGF2) activates the extracellular signal-regulated
      kinases 1 and 2 (ERK1/2) through its specific receptors. Interaction of FGF2 with
      cell-surface heparan sulfate proteoglycans has also been suggested to induce
      intracellular signals. Thus, we investigated whether FGF2 can stimulate ERK1/2
      activation through heparan sulfate proteoglycans using mechanisms that do not
      depend on receptor activation in vascular smooth muscle cells. The activation of
      FGF receptors was inhibited by treating cells with 5'-deoxy-5'methyl
      thioadenosine and by expressing truncated dominant-negative FGF receptors. In
      both cases, FGF2 was able to stimulate the phosphorylation of ERK1/2 despite the
      absence of detectable FGF receptor tyrosine kinase activity. The FGF2 activation
      of ERK1/2 in the absence of receptor activity was completely dependent on heparan
      sulfate, because this activity was abolished by heparinase III digestion of the
      cells. In contrast, heparinase III treatment of control cells, with functional
      FGF receptors, showed only slight changes in FGF2-mediated ERK1/2 activation
      kinetics. Thus, in addition to serving as coreceptors for FGF receptor
      activation, heparan sulfate proteoglycans might also function directly as
      receptors for FGF2-induced ERK1/2 activation. Activation of ERK1/2 via cell
      surface proteoglycans could have significant biological consequences, potentially
      directing cell response toward growth, migration, or differentiation.

PMID- 14684628
TI  - PPARalpha activators inhibit vascular endothelial growth factor receptor-2
      expression by repressing Sp1-dependent DNA binding and transactivation.
AB  - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated
      transcription factors, originally implicated in the regulation of lipid and
      glucose homeostasis. In addition, natural and synthetic PPAR activators may
      control inflammatory processes by inhibition of distinct proinflammatory genes.
      As signaling via the vascular endothelial growth factor receptor-2 (VEGFR2)
      pathway is critical for angiogenic responses during chronic inflammation, we
      explored whether known antiinflammatory effects of PPAR ligands are mediated in
      part through diminished VEGFR2 expression. In this study, PPARalpha agonists are
      found to inhibit endothelial VEGFR2 expression, whereas predominant PPARgamma
      ligands remained without discernible effects. Time- and concentration-dependent
      inhibition is demonstrated both at the level of protein and mRNA VEGFR2
      expression. Inhibitory effects of PPARalpha agonists on transcriptional activity
      of the VEGFR2 promoter are conveyed by an element located between base pairs -60
      and -37 that contains two adjacent consensus Sp1 transcription factor binding
      sites. Constitutive Sp1-containing complex formation to this sequence is
      decreased by PPARalpha treatment, indicating that VEGFR2 gene expression is
      inhibited by repressing Sp1 site-dependent DNA binding and transactivation. Our
      coimmunoprecipitation experiments revealed enhanced protein interactions between
      PPARalpha and Sp1 on PPARalpha activation, thus constituting a probable mechanism
      by which PPARalpha activators decrease Sp-dependent binding activity to the
      VEGFR2 promoter. Hence, molecular mechanisms by which PPARs modulate the rate of
      gene transcription may include direct interactions between specific transcription
      factors and PPARs that ultimately result in reduced DNA binding to their
      respective response elements.

PMID- 14684630
TI  - A New Year's resolution after a lost decade.

PMID- 14684629
TI  - Role of caspases in Ox-LDL-induced apoptotic cascade in human coronary artery
      endothelial cells.
AB  - Oxidized low-density lipoprotein (ox-LDL) induces apoptosis in endothelial cells.
      However, steps leading to ox-LDL-induced apoptosis remain unclear. We examined
      the role of ox-LDL and its newly described receptor LOX-1 in the expression of
      intracellular pro- and antiapoptotic proteins and caspase pathways in human
      coronary artery endothelial cells (HCAECs). Cells were cultured and treated with
      different concentrations (10 to 80 microg/mL) of ox-LDL for different times (2 to
      24 hours). Ox-LDL induced apoptosis in HCAECs in a concentration- and time
      dependent manner. Ox-LDL also activated caspase-9 and caspase-3, but not caspase
      8. After ox-LDL treatment, there was a significant release of activators of
      caspase-9, including cytochrome c and Smac from mitochondria to cytoplasmic
      compartment, and their release was not affected by treatment of cells with
      inhibitors of either caspase-8 or caspase-9. Ox-LDL also decreased expression of
      antiapoptotic proteins Bcl-2 and c-IAP (inhibitory apoptotic protein)-1, which
      are involved in the release of cytochrome c and Smac and activation of caspase-9,
      in a concentration- and time-dependent manner. On the other hand, ox-LDL did not
      change the expression of Fas-associated death domain-like interleukin-1beta
      converting enzyme-inhibitory protein (FLIP) and proapoptotic protein Fas, which
      are required for the activation of caspase-8. Further, ox-LDL did not cause the
      truncation of Bid, which implies the activation of caspase-8. In other
      experiments, pretreatment of HCAECs with the caspase-9 inhibitor z-LEHD-fmk, but
      not the caspase-8 inhibitor z-IETD-fmk, blocked ox-LDL-induced activation of
      caspase-3 and apoptosis. As expected, pretreatment with the caspase-3 inhibitor
      DEVD-CHO inhibited ox-LDL-induced activation of caspase-3 and resultant
      apoptosis. The proapoptotic effects of ox-LDL were mediated by its receptor LOX
      1, because pretreatment of HCAECs with antisense-LOX-1, but not sense-LOX-1,
      blocked these effects of ox-LDL. These findings suggest that ox-LDL through its
      receptor LOX-1 decreases the expression of antiapoptotic proteins Bcl-2 and c-IAP
      1. This is followed by activation of apoptotic signaling pathway, involving
      release of cytochrome c and Smac and activation of caspase-9 and then caspase-3.

PMID- 14684631
TI  - Providing the world with clean water.

PMID- 14684632
TI  - Clinical arithmetic.

PMID- 14684633
TI  - Dignity is a useless concept.

PMID- 14684634
TI  - Would the NHS benefit from a single, identifiable leader? An email conversation.

PMID- 14684635
TI  - The power of stories over statistics.

PMID- 14684636
TI  - The midwife, the coincidence, and the hypothesis.

PMID- 14684637
TI  - Thoughts for new medical students at a new medical school.

PMID- 14684638
TI  - How to make a silk purse from a sow's ear--a comprehensive review of strategies
      to optimise data for corrupt managers and incompetent clinicians.

PMID- 14684639
TI  - Get peered!

PMID- 14684640
TI  - HARLOT plc: an amalgamation of the world's two oldest professions.

PMID- 14684641
TI  - How to make a compelling submission to NICE: tips for sponsoring organisations.

PMID- 14684642
TI  - The psychiatric protection order for the "battered mental patient".

PMID- 14684643
TI  - Of Struldbruggs, sugar, and gatekeepers: a tale of our times.

PMID- 14684644
TI  - Audit of soap usage by a primary care team.

PMID- 14684645
TI  - Possible interaction between warfarin and cranberry juice.

PMID- 14684646
TI  - Car colour and risk of car crash injury: population based case control study.

PMID- 14684647
TI  - Depiction of elderly and disabled people on road traffic signs: international
      comparison.

PMID- 14684648
TI  - How long did their hearts go on? A Titanic study.

PMID- 14684649
TI  - Parachute use to prevent death and major trauma related to gravitational
      challenge: systematic review of randomised controlled trials.
AB  - OBJECTIVES: To determine whether parachutes are effective in preventing major
      trauma related to gravitational challenge. DESIGN: Systematic review of
      randomised controlled trials. DATA SOURCES: Medline, Web of Science, Embase, and
      the Cochrane Library databases; appropriate internet sites and citation lists.
      STUDY SELECTION: Studies showing the effects of using a parachute during free
      fall. MAIN OUTCOME MEASURE: Death or major trauma, defined as an injury severity
      score > 15. RESULTS: We were unable to identify any randomised controlled trials
      of parachute intervention. CONCLUSIONS: As with many interventions intended to
      prevent ill health, the effectiveness of parachutes has not been subjected to
      rigorous evaluation by using randomised controlled trials. Advocates of evidence
      based medicine have criticised the adoption of interventions evaluated by using
      only observational data. We think that everyone might benefit if the most radical
      protagonists of evidence based medicine organised and participated in a double
      blind, randomised, placebo controlled, crossover trial of the parachute.

PMID- 14684650
TI  - Medicine in Egypt at the time of Napoleon Bonaparte.

PMID- 14684651
TI  - Retroactive prayer: a preposterous hypothesis?

PMID- 14684652
TI  - Love and death in Wagner's Tristan und Isolde--an epic anticholinergic crisis.

PMID- 14684653
TI  - Signs of love, not a love potion.

PMID- 14684654
TI  - Football position and atopy--both subject to the birth order effect?

PMID- 14684656
TI  - Referee's half-time analysis.

PMID- 14684657
TI  - Australia versus New Zealand: an emotional meta-analysis of rugby.

PMID- 14684658
TI  - Why running is not for people.

PMID- 14684659
TI  - Alcohol screening in primary care.

PMID- 14684661
TI  - Misleading BMJ USA editorial.

PMID- 14684663
TI  - Relationship between blood glucose control, pathogenesis and progression of
      diabetic nephropathy.
AB  - The present review briefly discusses evidence that the risk of a rapid decline of
      glomerular function abruptly increases when glycated hemoglobin is steadily
      higher than 7.5% and postprandial blood glucose is >200 mg/dl. The capacity to
      accomplish and to maintain steadily tightly controlled blood glucose levels is
      scanty using the currently implemented hypoglycemic drugs. Moreover, it must be
      highlighted that most patients with type 2 diabetes, particularly when renal
      damage does occur, have arterial hypertension. Several studies suggested that the
      development of ESRD is prevented significantly better by drugs that modulate the
      renin angiotensin system than by other compounds in patients with type 1 and 2
      diabetes with overt diabetic nephropathy. However, a recent trial, the study
      Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial
      (ALLHAT), which compared lisinopril, chlorthalidone, and amlodipine in a large
      population of patients with arterial hypertension, either associated or not with
      diabetes, demonstrated that the development of both coronary heart diseases and
      renal complications was equally prevented by the three drugs. One word of caveat,
      however, needs to be raised concerning one of the results of the ALLHAT study:
      the higher risk of developing new-onset diabetes among hypertensive patients who
      are not treated with lisinopril. Even if it is true that this latter side effect
      was not accompanied by a worse outcome of macrovascular and renal complications
      during the 5-yr follow-up period, one cannot rule out the possibility that this
      might be the case during more prolonged periods of follow-up in the future. Thus,
      the advantage of a lower cost in the treatment of hypertension with diuretics as
      compared with other drugs, with similar degree of success in the prevention of
      vascular complications, should be weighed also taking into consideration the
      burden of a higher rate of occurrence of new-onset diabetes.

PMID- 14684662
TI  - Fetal origin of the GATA1 mutation in identical twins with transient
      myeloproliferative disorder and acute megakaryoblastic leukemia accompanying Down
      syndrome.

PMID- 14684664
TI  - Optimizing therapy in the diabetic patient with renal disease: antihypertensive
      treatment.
AB  - Hypertension, impaired renal function, and proteinuria are commonly associated to
      the presence of diabetes. They play a major role in the development of
      cardiovascular and renal damage. Effective antihypertensive treatment reduces the
      progression of diabetic nephropathy and improves cardiovascular prognosis.
      Accordingly, tight BP control (<130/80 mmHg) is currently recommended in diabetic
      patients. Achieving BP targets represents the most important determinant of
      cardiovascular and renal protection. However, it has been suggested that specific
      classes of antihypertensive drugs may exert additional organ protection beyond
      their BP control. The pharmacologic blockade of the renin-angiotensin-aldosterone
      system has been shown to convey greater renal and cardiovascular protection
      compared with other classes of drugs. In particular, studies focusing on renal
      end point suggest that angiotensin-converting enzyme inhibitors (ACEI) are the
      first-choice drugs in type 1 diabetes. Both ACEI and angiotensin II receptor
      blockers prevent the progression from microalbuminuria to clinical proteinuria in
      type 2 diabetes, but angiotensin blockers provide better renoprotection in
      patients with overt nephropathy. Regarding cardiovascular protection, several
      studies (but not all) have shown that ACEI exert a protective effect on diabetic
      patients. Recently, interesting results in favor of angiotensin receptor blockers
      have been reported in the IDNT, RENAAL, and LIFE studies. It should be noted that
      to achieve maximal renal and cardiovascular protection, most diabetic patients
      require integrated therapeutic intervention, including not only several
      antihypertensive drugs, but statins and antiplatelet therapy as well.

PMID- 14684665
TI  - Optimization of hypolipidemic and antiplatelet treatment in the diabetic patient
      with renal disease.
AB  - Because diabetes confers a very high risk of cardiovascular morbility and
      mortality, an aggressive hypolipidemic and antiplatelet treatment has been
      strongly recommended in the whole diabetic population. In particular, patients
      who have diabetes should be considered in "secondary prevention" even before
      presenting cardiovascular events, because diabetes is a "coronary heart disease
      equivalent." Furthermore, because renal failure is a cardiovascular risk factor
      per se, patients with diabetes and renal disease present an even greater risk for
      atherosclerotic vascular events and should be treated even more intensively with
      hypolipidemic and antiaggregating drugs: the presence of renal impairment does
      not justify a nihilist therapeutical approach, even if appropriate cautions are
      mandatory. Finally, dyslipidemia contributes to the deterioration of renal
      function, a phenomenon potentially prevented by hypolipidemic therapy.

PMID- 14684666
TI  - Hyperparathyroidism and anemia in uremic subjects: a combined therapeutic
      approach.
AB  - Several factors are involved in conditioning renal anemia, and a critical role is
      attributed to parathyroid hormone (PTH) oversecretion, which has some direct
      effects on endogenous erythropoietin (EPO) synthesis, bone marrow erythroid
      progenitors, and red cell survival. Indirect effects are mainly based on the
      induction of bone marrow fibrosis. Indirect evidence of the role of PTH is based
      on the observation that parathyroidectomy, when performed in uremic patients, is
      often followed by restoration of the hematocrit. The interpretations of such
      positive results are based on the observation of the restored bone marrow space
      after operation and also in a rise of immunoreactive EPO serum concentrations
      observed in the first weeks after gland removal. Another field of clinical
      interest is the possible beneficial effects of vitamin D therapy in controlling
      PTH secretion, which in turn determines an improvement of anemia of uremic
      subjects. Several uncontrolled studies confirmed this possibility, indicating
      that patients who respond to calcitriol or its analogs also show an increase of
      their hemoglobin levels. Thus, a combined therapeutic approach to PTH
      oversecretion and anemia is possible by intravenous calcitriol or
      parathyroidectomy pointing to the possible reversibility of bone marrow fibrosis,
      which is a common feature of secondary hyperparathyroidism. The increased
      sensitivity to EPO therapy can also induce a successful reduction of its dosage,
      thus allowing an interesting reduction of costs.

PMID- 14684667
TI  - Renal replacement therapy in patients with diabetes and end-stage renal disease.
AB  - The number of patients who have diabetes and ESRD and are being admitted to renal
      replacement treatment (RRT) is increasing dramatically worldwide, and in many
      countries, diabetes has become the single most frequent cause of ESRD. Although
      the prognosis of patients who have diabetes and are receiving RRT has greatly
      improved, survival and medical rehabilitation rates continue to be significantly
      worse than those of nondiabetic patients, mainly because of preexisting severely
      compromised cardiovascular conditions. The most common RRT modality in patients
      with diabetes is still hemodialysis, but it gives rise to a number of clinical
      problems, in particular difficulties in the management of the vascular access and
      high frequency of intradialytic hypotension. However, patients who have diabetes
      and are on peritoneal dialysis have to face a progressive increase in peritoneal
      permeability, loss of ultrafiltration, and peritoneal fibrosis, all phenomena
      being accelerated in patients with diabetes and ultimately leading to an
      increased technique failure. The results of observational studies and national
      registries, although conflicting, suggest that these two dialytic modalities are
      somehow comparable in terms of outcomes, whereas accumulating evidence shows that
      both survival and medical rehabilitation of patients with diabetes are
      significantly better after renal transplantation, which should be the first
      choice option for patients who have diabetes and reach ESRD but unfortunately
      still accounts for only a limited proportion of RRT treatments in these patients.

PMID- 14684668
TI  - Clinical usefulness of ambulatory blood pressure monitoring.
AB  - During the past decade, several prospective studies showed that ambulatory BP
      (ABP) measurements provide a better prediction of major cardiovascular events
      when compared with clinic BP measurements. This review summarizes the available
      evidence supporting the use of ABP monitoring to refine prognostic stratification
      in hypertension. On the basis of available evidence, an operational flowchart is
      suggested to interpret results of ABP for better treatment of patients with
      elevated BP.

PMID- 14684669
TI  - Cardiovascular and renal risk assessment as a guide for treatment in primary
      hypertension.
AB  - BP levels per se may be an unreliable indicator of risk in the individual
      patient. In fact, the global cardiovascular profile, including the presence and
      degree of target organ damage, is a better predictor of future events and,
      therefore, should be used to choose both treatment and BP goals. However, the
      prevalence of target organ damage and therefore the percentage of patients who
      are at risk very much depends on the diagnostic techniques used. However, as a
      result of the high prevalence of hypertension and its financial impact on public
      health systems, limiting unnecessary and extensive diagnostic tests also should
      be a priority. The routine search for microalbuminuria may lead to the detection
      of a significantly greater percentage of patients who are at high risk while
      contributing the optimization of the cost-effectiveness of diagnostic workup in
      hypertensive patients.

PMID- 14684670
TI  - Hypertensive renal damage in metabolic syndrome is associated with glucose
      metabolism disturbances.
AB  - Recent evidence highlights the relationship between metabolic syndrome (MS) and
      increased risk of cardiovascular (CV) diseases. Mild renal function abnormalities
      are associated with an enhanced CV risk, considered to be due to the presence of
      associated risk factors. Hence, MS and renal abnormalities could be linked and
      contribute to augment CV risk. For estimating the prevalence of diminished
      creatinine clearance (CC; <60 ml/min per 1.73 m(2)) in hypertensive patients with
      or without MS and for investigating the factors accompanying this abnormality,
      1625 hypertensive patients, aged 18 yr or older, were included. The presence of
      MS was defined according to the Adult Treatment Panel III criteria. The overall
      prevalence of MS was 49.4% (n = 802). No significant difference was found for CC
      between those with and without MS, albeit the presence of MS was accompanied by
      greater urinary albumin excretion (P = 0.01). The prevalence of a diminished CC
      was also similar in the two groups. MS-positive patients presented a progressive
      decay in CC when classified as normoglycemic (n = 319), impaired fasting glucose
      (n = 237), and diabetic patients (n = 246; 85.9 +/- 30.2, 81.8 +/- 26.8, and 75.2
      +/- 25.7 ml/min per 1.73 m(2), respectively; P = 0.0007 linearity test) and the
      opposite for microalbuminuria (29.5 +/- 45.5, 45.0 +/- 96.6, and 74.1 +/- 146.3
      mg/24 h, respectively; P = 0.001 linearity test). In multiple regression
      analysis, factors related to the finding of a diminished CC in MS and non-MS
      patients were similar. Hypertensive patients at a relatively young age present
      with an elevated prevalence of minor abnormalities of renal function that is
      mostly related to the presence of metabolic alteration of glucose together with
      age and BP.

PMID- 14684671
TI  - Low-salt diet and diuretic effect on blood pressure and organ damage.
AB  - This review focuses on some aspects of the complex relationship among dietary
      salt intake, BP, organ complication, and genetic factors. First, the reason
      regarding the debate in the effect of a low-salt diet on BP and organ damage is
      discussed. Certainly, the lack of controlled long-term studies, taken together
      with the opposite effect of a low-salt diet on cardiovascular risk factors,
      justifies the contrasting opinions about the opportunity to reduce the sodium
      (Na) content in the diet of the general population. Second, the contribution that
      the genetic polymorphisms may furnish to explain the BP response in studies that
      apply either a moderate or a brisk reduction of salt intake is considered.
      Finally, the long-term effects of diuretics that produce a decrease in body Na
      similar to that achieved by moderate long-term dietary salt reduction are
      examined. Diuretics are able to reduce organ complications in the general
      population. However, these beneficial effects may be the net results of opposite
      effects in a subset of patients. Recently, the results of an observational study
      on hypertensive patients who were treated with a variety of antihypertensive
      drugs have been published. These results show that in carriers of the 460Trp ADD1
      allele (38% of the population), the administration of diuretics halves the
      incidence of myocardial infarction and stroke when compared with other
      antihypertensive treatments that produce similar reduction of BP. These data
      support the notion that matching of the genetic mechanism with the drug
      mechanisms of action produces a clear therapeutic benefit.

PMID- 14684672
TI  - Dietary sodium and cardiovascular health in hypertensive patients: the case
      against universal sodium restriction.
AB  - Salt and BP have been linked for more than a century. Recent data indicate that,
      given free access to sodium, in most populations, intake is between 100 and 200
      mmol/d, although individual variation is wide. There is good evidence that
      individual differences are influenced by genetics, environment, and behavior.
      There is also solid clinical trial data suggesting that substantial reduction in
      sodium intake (75 to 100 mmol/d) will, on average, lower diastolic pressure by
      approximately 1 mmHg and systolic by approximately 3 to 5 mmHg. In addition,
      there is good evidence that sodium restriction is accompanied by other
      hemodynamic and nonhemodynamic effects. The health effect of sodium restriction
      can be assessed only by outcome study in humans. The best available evidence in
      this regard derives from observational study. The several available studies in
      the general population are inconsistent and demonstrate heterogeneity across
      subgroups in the relation of sodium intake to cardiovascular morbidity and
      mortality. Only a single study has been reported in hypertensive patients that
      links baseline sodium, measured by 24-h urinary excretion, and subsequent
      cardiovascular outcomes. In that study, controlling for other risk factors, there
      was a significant, independent, inverse association of urinary sodium excretion
      and coronary morbidity and mortality. Indeed, an increase of 66 mmol/24 h was
      associated with a 36% reduction in events. Taken together, these data provide no
      support for the notion that either normotensive or hypertensive individuals
      should routinely decrease (or increase) dietary sodium intake.

PMID- 14684673
TI  - Guidelines for antihypertensive treatment: an update after the ALLHAT study.
AB  - The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
      (ALLHAT) Study, the largest double-blind, randomized trial in hypertensive
      patients, confirmed and strengthened the clinical relevance of thiazide diuretics
      in the treatment of hypertension but did not prove the superiority of these
      drugs. Its claim of the superiority of chlorthalidone was based on some secondary
      outcomes, principally represented by (1) an increased incidence of stroke in the
      doxazosin and lisinopril arms, an effect that might be explained by differences
      in systolic BP; (2) greater morbidity but not mortality for congestive heart
      failure (CHF) in the doxazosin, amlodipine, and lisinopril arms, a finding that
      might reflect poor accuracy in the diagnosis and/or especially the switching from
      diuretic treatment in 90% of patients. Moreover, the ALLHAT study has other
      limitations, and its conclusions are in contrast with data from overall
      controlled clinical trials indicating that given the same BP reduction, the
      benefit of different drug classes is similar. As to whether the ALLHAT study will
      influence ongoing guidelines concerning the choice of antihypertensive drugs, the
      answer is "yes" if interpretation of its data in favor of diuretics and cost of
      drugs become the preponderant considerations, as it was in recent JNC VII
      guidelines. However, the more liberal approach based on the choice of all
      available drug classes seems still to be valid, as is in the ESH-ESC guidelines,
      if the preponderant consideration is that the real benefit of antihypertensive
      therapy is due to efficient BP control and not to a particular benefit of a
      single drug class.

PMID- 14684674
TI  - Mediators of diabetic renal disease: the case for tgf-Beta as the major mediator.
AB  - The critical role of hyperglycemia in the genesis of diabetic nephropathy has
      been established by cell culture studies, experimental animal models, and
      clinical trials. Certain cytokines and growth factors have been identified as
      likely mediators of the effects of high ambient glucose on the kidney, but
      prominent among these is TGF-beta, a prototypical hypertrophic and fibrogenic
      cytokine. Overexpression of TGF-beta has been demonstrated in the glomerular and
      tubulointerstitial compartments of experimental diabetic animals. The TGF-beta
      receptor signaling system is also triggered, as evidenced by upregulation of the
      TGF-beta type II receptor and activation of the downstream Smad signaling
      pathway. Treatment of diabetic mice with neutralizing anti-TGF-beta antibodies
      prevents the development of renal hypertrophy, mesangial matrix expansion, and
      the decline in renal function. Antibody therapy also reverses the established
      lesions of diabetic glomerulopathy. These studies argue strongly in support of
      the hypothesis that overactivity of the TGF-beta system in the kidney is a
      crucial mediator of diabetic renal hypertrophy and mesangial matrix expansion.

PMID- 14684675
TI  - Effects of smoking on systemic and intrarenal hemodynamics: influence on renal
      function.
AB  - In recent years, it has become apparent that smoking has a negative impact on
      renal function, being one of the most important remediable renal risk factors. It
      has been shown clearly that the risk for high-normal urinary albumin excretion
      and microalbuminuria is increased in smoking compared with nonsmoking subjects of
      the general population. Data from the Multiple Risk Factor Intervention Trial
      indicate that at least in men, smoking increases the risk to reach end-stage
      renal failure. Smoking is particularly "nephrotoxic" in older subjects, subjects
      with essential hypertension, and patients with preexisting renal disease. Of
      interest, the magnitude of the adverse renal effect of smoking seems to be
      independent of the underlying renal disease. Death-censored renal graft survival
      is decreased in smokers, indicating that smoking also damages the renal
      transplant. Cessation of smoking has been shown to reduce the rate of progression
      of renal failure both in patients with renal disease and in patients with a renal
      transplant. The mechanisms of smoking-induced renal damage are only partly
      understood and comprise acute hemodynamic (e.g., increase in BP and presumably
      intraglomerular pressure) and chronic effects (e.g., endothelial cell
      dysfunction). Renal failure per se leads to an increased cardiovascular risk. The
      latter is further aggravated by smoking. Particularly, survival of smokers with
      diabetes on hemodialysis is abysmal.

PMID- 14684676
TI  - ACE inhibition versus angiotensin receptor blockade: which is better for renal
      and cardiovascular protection?
AB  - Chronic renal disease is characterized by a gradual loss of renal function and an
      increased cardiovascular risk. Renin-angiotensin system blockade by angiotensin
      converting enzyme inhibition or angiotensin receptor blockade has distinct
      renoprotective and cardiovascular protective effects, but which of the two drug
      classes confers more protection is still a matter of debate. This review
      highlights and compares the effects of the two drug-classes in nondiabetic renal
      disease and in overt or incipient nephropathy of type 1 and type 2 diabetes. Both
      renal and cardiovascular outcomes are considered. Regardless of their relative
      efficacy, both drug classes have a dose-response relationship for intermediate
      renal and cardiovascular parameters. Moreover, combined treatment with
      angiotensin-converting enzyme inhibition and angiotensin receptor blockade seems
      to provide better long-term renoprotection than monotherapy. Actually, in most
      patients, achieving maximal renal and cardiovascular protection requires a
      multidrug regimen, usually including several antihypertensives. Within this
      approach, full dose titration of either RAS blocker followed by add-on with the
      second drug is more important than the choice of the initial drug.

PMID- 14684677
TI  - Angiotensin-converting enzyme inhibitors versus AT1 receptor antagonist in
      cardiovascular and renal protection: the case for AT1 receptor antagonist.
AB  - The development of pharmacologic agents that directly inhibit the angiotensin II
      receptor (angiotensin receptor blocker [ARB]) has provided clinicians with an
      alternative to the previously available angiotensin-converting enzyme inhibitors
      (ACEI) to downregulate the renin-angiotensin system. This review focuses on the
      available data that can guide the clinician to the use of these two classes of
      agents vis a vis their ability to provide cardiovascular (CV) and renal
      protection. Although the CV protective effect of ACEI in high-risk populations is
      widely appreciated, whether such an effect is entirely BP independent can be
      questioned. Most head-to-head comparisons between ACEI and ARB have yielded
      comparable CV protective effects, with ARB being associated with fewer adverse
      effects. Likewise, several-but not all-studies have demonstrated a CV protective
      effect of ACEI when compared with other active agents in patients with type 2
      diabetes. One study demonstrated a similar protection with ARB when compared with
      a beta blocker. In terms of renal protection, there are ample data to support a
      role for both ACEI and ARB to prevent the progression from microalbuminuria to
      overt albuminuria in both type 1 and type 2 diabetes. However, when progression
      of renal disease is used as an end point, protection has been demonstrated with
      ACEI only for type 1 but not type 2 diabetes. In this latter group, only ARB have
      been shown to slow progression to ESRD.

PMID- 14684678
TI  - Novel cardiovascular risk factors in end-stage renal disease.
AB  - Traditional risk factors only in part explain the risk differential between the
      general population and the population of patients with chronic nephropathies.
      Uncontrolled hyperphosphatemia and high calcium phosphate product constitute risk
      factors for cardiovascular calcifications, cardiac ischemia, and adverse
      cardiovascular outcomes, yet inflammation may be an even more important trigger
      of vascular calcification than these metabolic derangements. Homocysteine
      predicts cardiovascular events in ESRD, but evidence that this sulfur amino acid
      is directly implicated in the high cardiovascular mortality of uremic patients is
      still lacking. It seems unlikely that Chlamydia pneumoniae is a major risk factor
      in dialysis patients because the association between anti-Chlamydia antibodies
      and incident cardiovascular events seems to depend largely on the confounding
      effect of some traditional risk factors. Oxidative stress and raised plasma
      concentration of asymmetric dimethylarginine (ADMA) are pervasive in ESRD, and
      high ADMA in these patients may be at least in part the expression of the high
      rate of generation of oxidants. ADMA per se seems responsible for a 52% increase
      in the risk of death and for a 34% increase in the risk of cardiovascular events
      in dialysis patients.

PMID- 14684679
TI  - Increased sodium-lithium countertransport activity: a cellular dysfunction common
      to essential hypertension and diabetic nephropathy.
AB  - An increased activity of sodium-lithium countertransport (SLC) is a common
      finding in patients who have essential hypertension. The evidence that a similar
      dysfunction is shared also by patients with type 1 diabetes and nephropathy has
      suggested the hypothesis that a predisposition to essential hypertension may be
      the factor that, along with hyperglycemia, underlies the development of diabetic
      nephropathy. Despite the initial enthusiasm surrounding the potential use of SLC
      activity as a marker for the early detection and treatment of individuals who are
      predisposed to hypertension and diabetic nephropathy, its use has been so far
      restricted to epidemiologic studies, as specificity and sensitivity of the test
      are still too low to justify any clinical use. The recent finding, however, that
      the measurement of kinetic parameters of SLC can significantly increase the power
      to discriminate among individuals with and without hypertension or diabetic
      nephropathy could be of help toward a future clinical use of the measurement of
      this membrane transport. A second major point relates to the possibility that SLC
      per se might be directly involved in the pathogenesis of essential hypertension
      and diabetic nephropathy. This case has never been fully tested, as the gene
      responsible for this membrane transport has been, until recently, unknown. The
      recent identification of an alternative splicing of the first isoform of Na-H
      exchange that mediates SLC activity should allow for a rapid comprehension of the
      role of this transport in the pathophysiology of essential hypertension and
      diabetic nephropathy.

PMID- 14684680
TI  - Oxidative stress mediates apoptotic changes induced by hyperglycemia in human
      tubular kidney cells.
AB  - Reactive oxygen species (ROS) are important mediators for several biologic
      responses, including apoptosis. The present study evaluated the time course of
      changes in intracellular ROS production and apoptosis-related proteins, as well
      as apoptotic changes in human tubular proximal cells (HK-2 cells) exposed to
      hyperglycemia. Apoptosis (annexin V binding), ROS formation (fluorescence probe
      dichlorofluorescin diacetate and FACScan flow cytometry), and X chromosome-linked
      protein (XIAP; Western blot) were studied in HK-2 cells grown in a medium
      containing normal (NG) or high glucose (HG) concentrations (5.5 or 30 mM,
      respectively) for 18 to 48 h. HG promoted an increase (65% at 18 h and 73% at 24
      h; P < 0.05 versus NG) in intracellular ROS generation. At 18 h, the NF-kB
      binding activity (evaluated by electrophoretic mobility-shift assay) was
      suppressed by HG. At the same time, the expression of NF-kB-induced antiapoptotic
      XIAP was reduced in HG-treated cells. Apoptotic changes were observed at 48 h (34
      +/- 7% in HG versus 10 +/- 3% in NG; P < 0.001). Changes in ROS production at 24
      h predicted changes in the apoptotic index at 48 h (r = 0.96, P < 0.0001). These
      results suggest that hyperglycemia induces apoptotic changes in human tubular
      cells via an increase in oxidative stress and that a downregulation of
      antiapoptotic protein XIAP is a component of this response.

PMID- 14684681
TI  - Mild renal dysfunction and cardiovascular risk in hypertensive patients.
AB  - Mild renal dysfunction, defined as GFR <60 to 70 ml/min and/or the presence of
      increased urinary albumin excretion, is associated with higher cardiovascular
      morbidity and mortality in primary hypertension. The aim of the present study was
      to investigate the relationship between renal dysfunction and target organ damage
      (TOD), namely left ventricular hypertrophy (LVH), retinal vascular changes, and
      carotid atherosclerosis, in a large cohort of unselected middle-aged hypertensive
      patients with normal serum creatinine. A group of 934 untreated patients with
      primary hypertension (543 men, 391 women; mean age 50 +/- 11 yr) was studied.
      Renal function was estimated by the creatinine clearance using the Cockcroft
      Gault formula and by the presence of albuminuria, measured as the albumin to
      creatinine ratio (A/C) in first morning urine samples. LVH was determined
      according to electrocardiographic criteria, and retinal vascular changes were
      evaluated by direct ophthalmoscopy in all patients. In a subgroup of patients (n
      = 340; 208 men, 132 women; mean age 47 +/- 9), the presence and extent of cardiac
      and vascular organ damage was also assessed by ultrasound techniques. Creatinine
      clearance was on the average 82 +/- 20 ml/min. The overall prevalence of ECG
      detected LVH and retinopathy was 12 and 49%, respectively. Creatinine clearance
      was inversely related to duration of disease, systolic BP, serum glucose, total
      cholesterol, LDL cholesterol, and early signs of TOD, namely retinal vascular
      changes and LVH. Patients in the bottom quintile of creatinine clearance showed
      higher prevalence of both ECG-determined LVH (P = 0.04) and retinal vascular
      changes (P = 0.02). In the subgroup of patients who underwent ultrasound
      evaluation of cardiovascular structures, the prevalence of mild renal dysfunction
      was 18%, whereas the prevalence of LVH and carotid plaque was 49 and 26%,
      respectively. Patients with mild renal dysfunction showed higher left ventricular
      mass and increased intima-media thickness (P < 0.0001), as well as higher
      prevalence of LVH and carotid plaque as compared with those with normal renal
      function. Controlling for duration of hypertension and mean BP, the risk of TOD
      in our cohort increased by 20% for each 10 ml/min decrease in creatinine
      clearance and by 30% for each 0.2 mg/mmol increase in Log A/C. In conclusion,
      mild renal dysfunction is associated with preclinical end-organ damage in
      patients with primary hypertension. These data may help to explain the observed
      increase in cardiovascular mortality reported in these patients. The evaluation
      of creatinine clearance and urinary albumin excretion could be useful for
      identifying patients who are at higher cardiovascular risk.

PMID- 14684682
TI  - Molecular and functional analysis identifies ALK-1 as the predominant cause of
      pulmonary hypertension related to hereditary haemorrhagic telangiectasia.
AB  - BACKGROUND: Mutations of the transforming growth factor beta (TGFbeta) receptor
      components ENDOGLIN and ALK-1 cause the autosomal dominant vascular disorder
      hereditary haemorrhagic telangiectasia (HHT). Heterozygous mutations of the type
      II receptor BMPR2 underlie familial primary pulmonary hypertension. OBJECTIVE: To
      investigate kindreds presenting with both pulmonary hypertension and HHT.
      METHODS: Probands and families were identified by specialist pulmonary
      hypertension centres in five countries. DNA sequence analysis of ALK-1, ENDOGLIN,
      and BMPR2 was undertaken. Cellular localisation was investigated by heterologous
      overexpression of mutant constructs in both BAEC and HeLa cells. The impact of a
      novel sequence variant was assessed through comparative analysis and computer
      modelling. RESULTS: Molecular analysis of 11 probands identified eight missense
      mutations of ALK-1, one of which was observed in two families. Mutations were
      located within exons 5 to 10 of the ALK-1 gene. The majority of ALK-1 mutant
      constructs appeared to be retained within the cell cytoplasm, in the endoplasmic
      reticulum. A novel GS domain mutation, when overexpressed, reached the cell
      surface but is predicted to disrupt conformational changes owing to loss of a
      critical hydrogen bond. Two novel missense mutations were identified in ENDOGLIN.
      CONCLUSIONS: The association of pulmonary arterial hypertension and HHT
      identifies an important disease complication and appears most common among
      subjects with defects in ALK-1 receptor signalling. Future studies should focus
      on detailed molecular analysis of the common cellular pathways disrupted by
      mutations of ALK-1 and BMPR2 that cause inherited pulmonary vascular disease.

PMID- 14684683
TI  - Identification of a locus for type I punctate palmoplantar keratoderma on
      chromosome 15q22-q24.
AB  - BACKGROUND: The identification of the molecular basis of disorders of
      keratinisation has significantly advanced our understanding of skin biology,
      revealing new information on key structures in the skin, such as the intermediate
      filaments, desmosomes, and gap junctions. Among these disorders, there is an
      extraordinarily heterogeneous group known as palmoplantar keratodermas (PPK), for
      which only a few molecular defects have been described. A particular form of PPK,
      known as punctate PPK, has been described in a few large autosomal dominant
      pedigrees, but its genetic basis has yet to be identified. AIM: Identification of
      the gene for punctate PPK. METHODS: Clinical examination and linkage analysis in
      three families with punctate PPK. RESULTS: A genomewide scan was performed on an
      extended autosomal dominant pedigree, and linkage to chromosome 15q22-q24 was
      identified. With the addition of two new families with the same phenotype, we
      confirmed the mapping of the locus for punctate PPK to a 9.98 cM interval,
      flanked by markers D15S534 and D15S818 (maximum two point lod score of 4.93 at
      theta = 0 for marker D15S988). CONCLUSIONS: We report the clinical and genetic
      findings in three pedigrees with the punctate form of PPK. We have mapped a
      genetic locus for this phenotype to chromosome 15q22-q24, which indicates the
      identification of a new gene involved in skin integrity.

PMID- 14684684
TI  - A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing
      loss (DFNA20/26).
AB  - Linkage analysis in a multigenerational family with autosomal dominant hearing
      loss yielded a chromosomal localisation of the underlying genetic defect in the
      DFNA20/26 locus at 17q25-qter. The 6-cM critical region harboured the gamma-1
      actin (ACTG1) gene, which was considered an attractive candidate gene because
      actins are important structural elements of the inner ear hair cells. In this
      study, a Thr278Ile mutation was identified in helix 9 of the modelled protein
      structure. The alteration of residue Thr278 is predicted to have a small but
      significant effect on the gamma 1 actin structure owing to its close proximity to
      a methionine residue at position 313 in helix 11. Met313 has no space in the
      structure to move away. Moreover, the Thr278 residue is highly conserved
      throughout eukaryotic evolution. Using a known actin structure the mutation could
      be predicted to impair actin polymerisation. These findings strongly suggest that
      the Thr278Ile mutation in ACTG1 represents the first disease causing germline
      mutation in a cytoplasmic actin isoform.

PMID- 14684685
TI  - Somatic instability of the DNA sequences encoding the polymorphic polyglutamine
      tract of the AIB1 gene.
AB  - BACKGROUND: AIB1 contains a polymorphic polyglutamine tract (poly Q) that is
      encoded by a trinucleotide CAG repeat. Previously there have been conflicting
      results regarding the effect of the poly Q tract length on breast cancer. Since
      poly Q is not encoded by a perfect CAG repeat, the heterozygous polymorphic
      alleles need to be resolved, to understand the exact DNA sequences encoding poly
      Q. METHODS: Poly Q encoding sequences of AIB1 from 107 DNA samples, including
      breast cancer cell lines, sporadic primary breast tumours, and blood samples from
      BRCA1/BRCA2 mutation carriers and the general population, were resolved by
      PCR/cloning followed by sequencing of each individual clone. RESULTS: 25 distinct
      poly Q encoding sequence patterns were found. More than two distinct sequence
      patterns were found in a significantly higher proportion of tumours and cell
      lines than that of the general population, suggesting somatic instability. A
      significantly higher proportion of cancer cell lines or primary breast tumours
      than that of the general population contained rare sequence patterns. The
      proportion of sporadic breast tumours having at least one allele < or =27 repeats
      is significantly higher than that in the blood of BRCA1/BRCA2 mutation carrier
      breast cancer patients or the general population. CONCLUSION: The poly Q encoding
      DNA sequences are somatically unstable in tumour tissues and cell lines. A
      missense mutation and a very short glutamine repeat in primary tumours suggests
      that AIB1 activity may be modulated through poly Q, which in turn plays a role in
      the cotransactivation of gene expressions in breast cancers.

PMID- 14684686
TI  - Consequences of JAG1 mutations.
AB  - BACKGROUND: Alagille syndrome (AGS) is a multi-system, autosomal dominant
      disorder with highly variable expressivity, caused by mutations within the
      Jagged1 (JAG1) gene. METHODS: We studied 53 mutation positive relatives of 34 AGS
      probands to ascertain the frequency of clinical findings in JAG1 mutation
      carriers. RESULTS: Eleven of 53 (21%) mutation positive relatives had clinical
      features that would have led to a diagnosis of AGS. Seventeen of the 53 (32%)
      relatives had mild features of AGS, revealed only after targeted evaluation
      following the diagnosis of a proband in their family. Twenty five of the 53 (47%)
      mutation positive relatives did not meet clinical criteria, and two of these
      individuals had no features consistent with AGS at all. The frequency of cardiac
      and liver disease was notably lower in the relatives than in the probands,
      characterising the milder end of the phenotypic spectrum. The characteristic
      facies of AGS was the feature with the highest penetrance, occurring almost
      universally in mutation positive probands and relatives. CONCLUSIONS: This study
      has implications for genetic counselling of families with AGS and JAG1 mutations.

PMID- 14684687
TI  - Recurrent de novo mitochondrial DNA mutations in respiratory chain deficiency.
AB  - Starting from a cohort of 50 NADH-oxidoreductase (complex I) deficient patients,
      we carried out the systematic sequence analysis of all mitochondrially encoded
      complex I subunits (ND1 to ND6 and ND4L) in affected tissues. This approach
      yielded the unexpectedly high rate of 20% mutation identification in our series.
      Recurrent heteroplasmic mutations included two hitherto unreported (T10158C and
      T14487C) and three previously reported mutations (T10191C, T12706C and A13514G)
      in children with Leigh or Leigh-like encephalopathy. The recurrent mutations
      consistently involved T-->C transitions (p<10(-4)). This study supports the view
      that an efficient molecular screening should be based on an accurate
      identification of respiratory chain enzyme deficiency.

PMID- 14684688
TI  - Novel ENAM mutation responsible for autosomal recessive amelogenesis imperfecta
      and localised enamel defects.
AB  - The genetic basis of non-syndromic autosomal recessive forms of amelogenesis
      imperfecta (AI) is unknown. To evaluate five candidate genes for an aetiological
      role in AI. In this study 20 consanguineous families with AI were identified in
      whom probands suggested autosomal recessive transmission. Family members were
      genotyped for genetic markers spanning five candidate genes: AMBN and ENAM
      (4q13.3), TUFT1 (1q21), MMP20 (11q22.3-q23), and KLK4 (19q13). Genotype data were
      evaluated to identify homozygosity in affected individuals. Mutational analysis
      was by genomic sequencing. Homozygosity linkage studies were consistent for
      localisation of an AI locus in three families to the chromosome 4q region
      containing the ENAM gene. ENAM sequence analysis in families identified a 2 bp
      insertion mutation that introduced a premature stop codon in exon 10. All three
      probands were homozygous for the same g.13185_13186insAG mutation. These probands
      presented with a generalised hypoplastic AI phenotype and a class II openbite
      malocclusion. All heterozygous carriers of the g.13185_13186insAG mutation had
      localised hypoplastic enamel pitting defects, but none had AI or openbite. The
      phenotype associated with the g.13185_13186insAG ENAM mutation is dose dependent
      such that ARAI with openbite malocclusion segregates as a recessive trait, and
      enamel pitting as a dominant trait.

PMID- 14684689
TI  - Rapid, high throughput prenatal detection of aneuploidy using a novel
      quantitative method (MLPA).

PMID- 14684690
TI  - A novel mutation in a patient with insulin-like growth factor 1 (IGF1)
      deficiency.

PMID- 14684691
TI  - APOE and TGF-beta1 genes are associated with obesity phenotypes.

PMID- 14684692
TI  - Inbreeding and risk of late onset complex disease.

PMID- 14684693
TI  - Association of single nucleotide polymorphisms in the oxidised LDL receptor 1
      (OLR1) gene in patients with acute myocardial infarction.

PMID- 14684694
TI  - Congenital abnormalities reported in Pelger-Huet homozygosity as compared to
      Greenberg/HEM dysplasia: highly variable expression of allelic phenotypes.

PMID- 14684695
TI  - A recurrent R718W mutation in COMP results in multiple epiphyseal dysplasia with
      mild myopathy: clinical and pathogenetic overlap with collagen IX mutations.

PMID- 14684696
TI  - Patient with bilateral periventricular nodular heterotopia and polymicrogyria
      with apparently balanced reciprocal translocation t(1;6)(p12;p12.2) that
      interrupts the mannosidase alpha, class 1A, and glutathione S-transferase A2
      genes.

PMID- 14684697
TI  - Greenberg dysplasia (HEM) and lethal X linked dominant Conradi-Hunermann
      chondrodysplasia punctata (CDPX2): presentation of two cases with overlapping
      phenotype.

PMID- 14684698
TI  - Renoprotective efficacy of renin-angiotensin inhibitors in IgA nephropathy is
      influenced by ACE A2350G polymorphism.

PMID- 14684699
TI  - Mutation screening of Mre11 complex genes: indication of RAD50 involvement in
      breast and ovarian cancer susceptibility.

PMID- 14684700
TI  - Mutation analysis of the lamin A/C gene (LMNA) among patients with different
      cardiomuscular phenotypes.

PMID- 14684701
TI  - Rapp-Hodgkin and AEC syndromes due to a new frameshift mutation in the TP63 gene.

PMID- 14684702
TI  - Antigen-independent expansion of CD28hi CD8 cells from aged mice: cytokine
      requirements and signal transduction pathways.
AB  - Memory CD8+ T cells from old mice can proliferate in nonirradiated recipients.
      Transfer of labeled cells from aged donors into young recipients showed that
      proliferation of aged donor CD8 cells requires host cells that can both respond
      to interferon-gamma and produce interleukin-15. Reisolation of transferred CD8
      cells from host mice showed that LAT (linker for activated T cells) translocation
      to the immunological synapse, and translocation of NF (nuclear factor)-kappaB to
      the nucleus were diminished in recovered CD8 T cells from old donors, whether
      they had divided in vivo or not. Cells able to proliferate in vivo could be
      isolated based on their unusually high levels of CD28 expression, but were found
      not to differ from other aged CD8 cells in their low levels of LAT and protein
      kinase C-theta (PKC-theta) translocation to the immunological synapse. Thus in
      vivo proliferation of CD28hi CD8 cells from aged mice cannot be attributed to
      retention of T-cell receptor signaling.

PMID- 14684703
TI  - Age-dependent decline of in vitro migration (basal and stimulated by IGF-1 or
      insulin) of human vascular smooth muscle cells.
AB  - Since biological aging causes a decrease in functions such as cell proliferation,
      we have studied the possible effect of age on the migration capacity of human
      vascular smooth muscle cells (SMCs). To this aim, the migration activity of
      cultured SMCs from arteries of male human donors ranging in age from 43-77 years
      was determined in a Boyden chamber, under basal conditions and after insulin-like
      growth factor-1 (IGF-1) or insulin stimulation. Migration activity decreased with
      donor age (r2 = 87%, 85%, and 78%, respectively). IGF-1 and insulin significantly
      reduced the age-dependent relationship observed in basal conditions, so that,
      comparing young with old, both IGF-1 and insulin stimulated SMC migration
      similarly, although the effect of age remained in absolute terms. In this
      article, we conclude that the age-dependent decline of migration activity-
      similar to what has already been shown for SMC proliferation--may be part of the
      biological ageing phenotype, which is not overcome by hormone stimulation.

PMID- 14684704
TI  - Exceptional longevity in pet dogs is accompanied by cancer resistance and delayed
      onset of major diseases.
AB  - To characterize extreme aged pet dogs as a first step in developing an animal
      model of exceptional longevity, we constructed lifetime medical histories for 345
      Rottweiler dogs using information collected from owners and veterinarians.
      Extreme aged dogs (alive at the 95th percentile age at death for the study
      population, > or =13.3 years) were compared with a usual longevity group (9-10
      years). Exceptional longevity in Rottweiler dogs was accompanied by a significant
      delay in the onset of major life-threatening diseases; 76% of extreme aged dogs
      remained free of all major diseases during the first 9 years of life. Only 19% of
      extreme aged dogs died of cancer versus 82% of dogs with usual longevity (p
      <.0001). The reduction in cancer mortality in oldest-old pet dogs mimics that
      seen in human centenarians and provides strong rationale for using this animal
      model to study comparative mechanisms of cancer resistance in the extreme aged.

PMID- 14684705
TI  - Interleukin-6 (IL6) genotype is associated with fat-free mass in men but not
      women.
AB  - We studied the association of the G-174C promoter polymorphism in the interleukin
      6 gene (IL6) with total body fat and fat-free mass (FFM) in 242 men and women
      (IL6 genotypes: G/G, n = 87; G/C, n = 100; C/C, n = 55) across the adult age span
      (21-92 years). In men, but not women (significant genotype by sex interactions; p
      =.023-.048), the C/C group exhibited significantly lower total FFM than the G/G
      group (54.7 +/- 0.8 kg vs 57.2 +/- 0.7 kg, respectively, p =.020), as well as
      significantly lower FFM of the lower limbs compared with the G/G group (18.4 +/-
      0.3 kg vs 19.8 +/- 0.3 kg, respectively, p =.004). No significant genotype
      differences were observed in total body fat mass in either men or women. The
      results indicate that the IL6 G-174C polymorphism is significantly associated
      with FFM in men but not women.

PMID- 14684707
TI  - The mechanisms of androgen effects on body composition: mesenchymal pluripotent
      cell as the target of androgen action.
AB  - Testosterone supplementation increases muscle mass primarily by inducing muscle
      fiber hypertrophy; however, the mechanisms by which testosterone exerts its
      anabolic effects on the muscle are poorly understood. The prevalent view is that
      testosterone improves net muscle protein balance by stimulating muscle protein
      synthesis, decreasing muscle protein degradation, and improving the reutilization
      of amino acids. However, the muscle protein synthesis hypothesis does not
      adequately explain testosterone-induced changes in fat mass, myonuclear number,
      and satellite cell number. We postulate that testosterone promotes the commitment
      of pluripotent stem cells into the myogenic lineage and inhibits their
      differentiation into the adipogenic lineage. The hypothesis that the primary site
      of androgen action is the pluripotent stem cell provides a unifying explanation
      for the observed reciprocal effects of testosterone on muscle and fat mass.

PMID- 14684708
TI  - Gene transfer to the nervous system: prospects for novel treatments directed at
      diseases of the aging nervous system.
AB  - In the past 3 decades, gene therapy has moved from a theoretical construct to an
      active field of basic research, animal studies, and clinical trials. In this
      article, we describe the conceptual basis underlying the use of gene therapy for
      diseases of the aging nervous system, the principal techniques used for gene
      delivery, and review preclinical animal studies in 4 different classes of
      neurologic dysfunction: 1) focal neuronal degeneration in the central nervous
      system; 2) global neuronal dysfunction in the central nervous system; 3)
      degenerative disease affecting components of the peripheral nervous system; and
      4) intractable focal pain. The full potential of this approach will not be
      established until the human trials are completed.

PMID- 14684709
TI  - Function in elderly cancer survivors depends on comorbidities.
AB  - BACKGROUND: Factors associated with functional status in elderly cancer
      survivors, in particular, comorbidity, have been inadequately studied. METHODS:
      Of 4162 participants aged 65 and older enrolled in the Duke Established
      Populations for Epidemiologic Studies of the Elderly study in 1986, 376 of the
      participants self-reported a diagnosis of cancer. Participants were divided into
      2 comorbidity groups and 4 cancer groups. Cancer groups included 132 participants
      diagnosed 0-4 years ago, 117 diagnosed 5-15 years ago, 127 diagnosed >15 years
      ago, and 3784 participants who had never been diagnosed with cancer. Comorbidity
      (self-reported stroke, diabetes, hypertension, and myocardial infarction) was
      classified as presence of 1 or no comorbidities (n = 3089) or 2 or more
      comorbidities (n = 1073). Function was assessed by Katz Activities of Daily
      Living, Rosow-Breslau, Nagi, and Instrumental Activities of Daily Living scales
      at the time of interview. RESULTS: In a two-way analysis of covariance model of
      comorbidity and cancer group controlling for age, race, sex, education, marital
      status, depression, and cognitive status, duration of cancer survivorship does
      not influence most measures of function. In the subset of 376 cancer survivors,
      comorbidity significantly correlates with the functional status of these older
      cancer survivors (<0.02, for all 4 measures of function). CONCLUSIONS: In the
      older cancer survivor, regardless of duration following diagnosis, the presence
      of comorbidity rather than the history of cancer per se correlates with impaired
      functional status.

PMID- 14684710
TI  - Trajectories of leg strength and gait speed among sedentary older adults:
      longitudinal pattern of dose response.
AB  - BACKGROUND: Current theory about how an older adult's leg strength influences
      walking speed is based primarily on nonlinear patterns of association observed in
      cross-sectional data. Compared with adults with normal or high levels of leg
      muscle strength, weak older adults are thought to have a greater capacity for
      functional change in response to changes in lower extremity strength.
      Longitudinal data, however, have not been applied to study this putative pattern
      of dose response. METHODS: Three repeated measures of leg strength, gait speed,
      and covariates were evaluated in a cohort of 134 sedentary, community-dwelling
      male and female participants (aged >64 years) of a randomized exercise
      intervention. Empirical Bayes methods were used to evaluate the association
      between trajectories of strength and gait speed during the course of the study.
      RESULTS: We observed a potentially clinically important, positive linear
      association between strength change and gait speed change. Each additional unit
      increase in the monthly rate of strength change increased the rate of gait speed
      change by 0.29 meters/minute/month (95% CI [confidence interval] = 0.03, 0.55
      m/min/mo). Absolute change in walking velocity due to strength changes in the
      cohort ranged from a gain of approximately 15 m/min to a loss of approximately 13
      m/min over the 9-month period (changes of -18% to +20% relative to a normal
      walking speed of 72 m/min). CONCLUSIONS: In this cohort, change in functional
      walking speed depended more on the rate of strength change observed than on the
      amount of muscle weakness present at baseline. These results have important
      implications for screening and intervention programs designed to change
      functional walking ability among sedentary older adults.

PMID- 14684711
TI  - Association of plasma homocysteine in elderly persons with atherosclerotic
      vascular disease and dementia, atherosclerotic vascular disease without dementia,
      dementia without atherosclerotic vascular disease, and no dementia or
      atherosclerotic vascular disease.
AB  - BACKGROUND: Increased plasma homocysteine has been associated with
      atherosclerotic vascular disease in elderly persons. The Framingham Study found
      that plasma homocysteine was a risk factor for dementia and Alzheimer's disease.
      METHODS: We investigated in an academic nursing home the association of plasma
      homocysteine with atherosclerotic vascular disease plus dementia (group 1),
      atherosclerotic vascular disease without dementia (group 2), dementia without
      atherosclerotic vascular disease (group 3), and no dementia or atherosclerotic
      vascular disease (group 4). RESULTS: The mean plasma homocysteine level was 15.3
      +/- 3.0 micromol/L in 50 group 1 patients, 15.1 +/- 2.7 micromol/L in 50 group 2
      patients, 14.4 +/- 2.7 micromol/L in 50 group 3 patients, and 10.6 +/- 3.2
      micromol/L in 50 group 4 patients (p <.0001 for group 1 vs group 4, for group 2
      vs group 4, and for group 3 vs group 4). CONCLUSIONS: The mean plasma
      homocysteine level was significantly higher in elderly patients with
      atherosclerotic vascular disease plus dementia, atherosclerotic vascular disease
      without dementia, and dementia without atherosclerotic vascular disease than in
      patients with no dementia or atherosclerotic vascular disease.

PMID- 14684712
TI  - Does antidepressant therapy improve cognition in elderly depressed patients?
AB  - OBJECTIVES: To analyze the effects of antidepressants on cognitive functioning in
      elderly depression. METHODS: Data were pooled for elderly participants with major
      depression from two double-blind 12-week studies (n = 444) comparing sertraline
      to fluoxetine and to nortriptyline. A cognitive battery was performed pre
      treatment and post-treatment that included the Shopping List Task (SLT), which
      quantifies short-term and long-term memory storage and retrieval, and the Digit
      Symbol Substitution Test (DSST), which measures visual tracking, motor
      performance, and coding. RESULTS: Older age, male gender, higher systolic blood
      pressure, and higher illness severity were associated with lower performance on
      specific cognitive measures at baseline. For the entire group, improved
      depression and a lower anticholinergic side effect (dry mouth and constipation)
      severity were associated with statistically significant improvement in the SLT
      and DSST. The correlations between improvements in depression and improvement in
      tested cognitive function were highest for sertraline followed by nortriptyline
      and then fluoxetine. CONCLUSIONS: Acute improvement in depression is associated
      with cognitive improvement as measured by the SLT and DSST. Prospective studies
      are warranted to study the effects of potential differences among antidepressant
      therapies on long-term cognitive outcomes in geriatric depression.

PMID- 14684713
TI  - Cognitive impairment modulates the effect of depressive symptoms on mortality in
      elderly people.

PMID- 14684714
TI  - Commentary on Goodwin's "Embracing complexity: a consideration of hypertension in
      the very old".

PMID- 14684716
TI  - Air pollution and poverty: does the sword cut both ways?

PMID- 14684717
TI  - Urban air pollution, health, and equity.

PMID- 14684719
TI  - Places and health.
AB  - This glossary aims to provide readers with some key conceptual tools with which
      to address the issue of place and health; it is hoped that it will provoke
      thought and debate on the range of ways that places are connected to health.

PMID- 14684720
TI  - Association between ambient air pollution and birth weight in Sao Paulo, Brazil.
AB  - OBJECTIVES: Previous studies have implicated air pollution in increased mortality
      and morbidity, especially in the elderly population and children. More recently,
      associations with mortality in infants and with some reproductive outcomes have
      also been reported. The aim of this study is to explore the association between
      exposure to outdoor air pollution during pregnancy and birth weight. DESIGN:
      Cross sectional study using data on all singleton full term live births during a
      one year period. For each individual birth, information on gestational age, type
      of delivery, birth weight, sex, maternal education, maternal age, place of
      residence, and parity was available. Daily mean levels of PM(10), sulphur
      dioxide, nitrogen dioxide, carbon monoxide, and ozone were also gathered. The
      association between birth weight and air pollution was assessed in regression
      models with exposure averaged over each trimester of pregnancy. SETTING: Sao
      Paulo city, Brazil. RESULTS: Birth weight was shown to be associated with length
      of gestation, maternal age and instruction, infant gender, number of antenatal
      care visits, parity, and type of delivery. On adjusting for these variables
      negative effects of exposure to PM(10) and carbon monoxide during the first
      trimester were observed. This effect seemed to be more robust for carbon
      monoxide. For a 1 ppm increase in mean exposure to carbon monoxide during the
      first trimester a reduction of 23 g in birth weight was estimated. CONCLUSIONS:
      The results are consistent in revealing that exposure to air pollution during
      pregnancy may interfere with weight gain in the fetus. Given the poorer outlook
      for low birthweight babies on a number of health outcomes, this finding is
      important from the public health perspective.

PMID- 14684722
TI  - Traffic related air pollution and incidence of childhood asthma: results of the
      Vesta case-control study.
AB  - STUDY OBJECTIVE: The Vesta project aims to assess the role of traffic related air
      pollution in the occurrence of childhood asthma. DESIGN AND SETTING: Case-control
      study conducted in five French metropolitan areas between 1998 and 2000. A set of
      217 pairs of matched 4 to 14 years old cases and controls were investigated. An
      index of lifelong exposure to traffic exhausts was constructed, using
      retrospective information on traffic density close to all home and school
      addresses since birth; this index was also calculated for the 0-3 years age
      period to investigate the effect of early exposures. MAIN RESULTS: Adjusted on
      environmental tobacco smoke, personal and parental allergy, and several
      confounders, lifelong exposure was not associated with asthma. In contrast,
      associations before age of 3 were significant: odds ratios for tertiles 2 and 3
      of the exposure index, relative to tertile 1, exhibited a positive trend (1.48
      (95%CI = 0.7 to 3.0) and 2.28 (1.1 to 4.6)), with greater odds ratios among
      subjects with positive skin prick tests. CONCLUSIONS: These results suggest that
      traffic related pollutants might have contributed to the asthma epidemic that has
      taken place during the past decades among children.

PMID- 14684723
TI  - Environmental justice: frequency and severity of US chemical industry accidents
      and the socioeconomic status of surrounding communities.
AB  - STUDY OBJECTIVES: The Clean Air Act Amendments of 1990 requires that chemical
      facilities in the US with specified quantities of certain toxic or flammable
      chemicals file a five year history of accidents. This study considers the
      relation between the reported accidents and surrounding community
      characteristics. DESIGN: This study is a retrospective analysis of the
      association between the demographics of counties in which facilities are located
      and the risk of accidental chemical release and resulting injuries at those
      facilities. The "location risk" (the risk that a facility having large volumes of
      hazardous chemicals is located in a community) and "operations risk" (the risk of
      an accident itself) are investigated. SETTING: 1994-2000 accident history data
      from 15 083 US industrial facilities using one or more of 140 flammable or toxic
      substances above a threshold level. Demographic makeup of 2333 counties
      surrounding these facilities was determined from the 1990 US census. MAIN
      RESULTS: Larger and more chemical intensive facilities tend to be located in
      counties with larger African-American populations and in counties with both
      higher median incomes and high levels of income inequality. Even after adjusting
      for location risk there is greater risk of accidents for facilities in heavily
      African-American counties (OR of accident = 1.9, 95% CI = 1.5 to 2.4).
      CONCLUSIONS: Further research and policy interventions are required to reduce the
      probability of locating facilities in an inequitable fashion, as well as health
      surveillance, and regulatory monitoring and enforcement activities to ensure that
      hazardous facilities in minority communities prepare and prevent accidental
      chemical releases to the same standards as elsewhere.

PMID- 14684724
TI  - Do socioeconomic characteristics modify the short term association between air
      pollution and mortality? Evidence from a zonal time series in Hamilton, Canada.
AB  - STUDY OBJECTIVE: To assess the short term association between air pollution and
      mortality in different zones of an industrial city. An intra-urban study design
      is used to test the hypothesis that socioeconomic characteristics modify the
      acute health effects of ambient air pollution exposure. DESIGN: The City of
      Hamilton, Canada, was divided into five zones based on proximity to fixed site
      air pollution monitors. Within each zone, daily counts of non-trauma mortality
      and air pollution estimates were combined. Generalised linear models (GLMs) were
      used to test mortality associations with sulphur dioxide (SO(2)) and with
      particulate air pollution measured by the coefficient of haze (CoH). MAIN
      RESULTS: Increased mortality was associated with air pollution exposure in a
      citywide model and in intra-urban zones with lower socioeconomic characteristics.
      Low educational attainment and high manufacturing employment in the zones
      significantly and positively modified the acute mortality effects of air
      pollution exposure. DISCUSSION: Three possible explanations are proposed for the
      observed effect modification by education and manufacturing: (1) those in
      manufacturing receive higher workplace exposures that combine with ambient
      exposures to produce larger health effects; (2) persons with lower education are
      less mobile and experience less exposure measurement error, which reduces bias
      toward the null; or (3) manufacturing and education proxy for many social
      variables representing material deprivation, and poor material conditions
      increase susceptibility to health risks from air pollution.

PMID- 14684725
TI  - Influence of socioeconomic conditions on air pollution adverse health effects in
      elderly people: an analysis of six regions in Sao Paulo, Brazil.
AB  - STUDY OBJECTIVE: To evaluate if the effects of particulate matter (PM(10)) on
      respiratory mortality of elderly people are affected by socioeconomic status.
      DESIGN: Time series studies. The daily number of elderly respiratory deaths were
      modelled in generalised linear Poisson regression models controlling for long
      term trend, weather, and day of the week, from January 1997 to December 1999, in
      six different regions of Sao Paulo City, Brazil. The regions were defined
      according to the proximity of air pollution monitoring stations. Three
      socioeconomic indicators were used: college education, monthly income, and
      housing. MAIN RESULTS: For a 10 micro g/m(3) increase in PM(10), the percentage
      increase in respiratory mortality varied from 1.4% (95% CI 5.9 to 8.7) to 14.2%
      (95% CI 0.4 to 28.0). The overall percentage increase in the six regions was 5.4%
      (95% CI 2.3 to 8.6). The effect of PM(10) was negatively correlated with both
      percentage of people with college education and high family income, and it was
      positively associated with the percentage of people living in slums. CONCLUSIONS:
      These results suggest that socioeconomic deprivation represents an effect
      modifier of the association between air pollution and respiratory deaths.

PMID- 14684726
TI  - Educational level and risk profile of cardiac patients in the EUROASPIRE II
      substudy.
AB  - STUDY OBJECTIVE: To ascertain, whether, conventional risk factors and readiness
      of coronary patients to modify their behaviour and to comply with recommended
      medication were associated with education in patients with established coronary
      heart disease. DESIGN AND METHODS: EUROASPIRE II was a cross sectional survey
      undertaken in 1999-2000 in 15 European countries to ascertain how effectively
      recommendations on coronary preventions are being followed in clinical practice.
      Consecutive patients, men and women </=71 years who had been hospitalised for
      acute coronary syndrome or revascularisation procedures, were identified
      retrospectively. Data were collected through a review of medical records,
      interview, and examination at least six months after hospitalisation. The
      education reached was ascertained at the interview. MAIN RESULTS: A total of 5556
      patients (1319 women) were evaluated. Significantly more patients with ischaemia
      had only primary education, in contrast with the remaining diagnostic groups.
      Body mass index and glucose were negatively associated with educational level,
      while HDL-cholesterol was positively associated. Men with highest education had
      significantly lower systolic blood pressure and total cholesterol. The prevalence
      of current smoking decreased significantly from primary to secondary and high
      education only in men. Both men and women with primary educational level were
      more often treated with antidiabetics, and antihypertensives, but less often with
      lipid lowering drugs. The effectiveness of treatment was virtually the same in
      all education groups. CONCLUSIONS: Patients with higher education had lower
      global coronary risk, than those with lower education. This should be considered
      in clinical practice. Particular strategies for risk communication and
      counselling are needed for those with lower education status.

PMID- 14684727
TI  - Partnership history and mental health over time.
AB  - STUDY OBJECTIVE: To describe the mental health of men and women with differing
      histories of partnership transitions. DESIGN: Data from nine waves of the British
      Household Panel Survey, a stratified general population sample, were used to
      calculate age standardised ratios and 95% confidence intervals for mean General
      Health Questionnaire scores for groups with different partnership transition
      histories. PARTICIPANTS: 2127 men and 2303 women aged under 65 who provided full
      interviews at every survey wave. MAIN RESULTS: Enduring first partnerships were
      associated with good mental health. Partnership splits were associated with
      poorer mental health, although the reformation of partnerships partially reversed
      this. Cohabiting was more beneficial to men's mental health, whereas marriage was
      more beneficial to women's mental health. The more recently a partnership split
      had occurred the greater the negative outcome for mental health. Women seemed
      more adversely affected by multiple partnership transitions and to take longer to
      recover from partnership splits than men. Single women had good mental health
      relative to other women but the same was not true for single men relative to
      other male partnership groups. CONCLUSIONS: Partnership was protective of mental
      health. Mental health was worse immediately after partnership splits, and the
      negative outcomes for health were longer lasting in women. Future work should
      consider other factors that may mediate, confound, or jointly determine the
      relation between partnership change and health.

PMID- 14684728
TI  - Neighbourhood social participation and women's use of anxiolytic-hypnotic drugs:
      a multilevel analysis.
AB  - STUDY OBJECTIVES: To identify and quantify a hypothesised collective effect of
      the neighbourhood on individual use of anxiolytic-hypnotic drugs (AHD). To
      analyse the general impact of neighbourhood social participation on use of AHD,
      adjusting for individual characteristics. DESIGN: Cross sectional analysis
      performed by multilevel logistic regression with women at the first level and
      neighbourhoods at the second level. SETTING: Malmo (250 000 inhabitants), Sweden.
      PARTICIPANTS: 15 456 women aged 45 to 73, residing in 95 neighbourhoods in Malmo,
      who took part in the Malmo diet and cancer study (1991-1996). MAIN RESULTS: The
      prevalence of AHD use was 5.5% in the study sample. Overall, 1.7% of the total
      individual differences in the propensity for using AHD were explained by the
      neighbourhood level. This percentage, however, differed between different
      individuals. Low level of social participation in the neighbourhood was
      associated with higher probability of AHD use (OR = 3.10 (95% CI 1.51 to 6.41)),
      independently of individual age, low social participation, low educational level,
      and living alone. This association was reduced (OR = 2.01 (95% CI 0.97 to 4.14))
      after the additional accounting for individual disability pension, low self rated
      health, stress, and medication for somatic disorders. CONCLUSIONS: The
      neighbourhood level of social participation seems to affect individual use of
      AHD, possibly through individual characteristics. However, neighbourhood
      boundaries play a minor part in understanding individual AHD use in the city of
      Malmo.

PMID- 14684729
TI  - Physical violence, self rated health, and morbidity: is gender significant for
      victimisation?
AB  - STUDY OBJECTIVE: To analyse gender differences in associations between physical
      violence and self rated health and self reported morbidity among a random sample
      of adults in Denmark. DESIGN AND SETTING: Two questions on self rated health and
      self reported morbidity respectively, were obtained from a cross sectional
      national health interview survey conducted among 12 028 adults (16 years +) in
      Denmark in 2000. A question on six different forms of physical violence was
      obtained from a supplementary self administered questionnaire given to the same
      sample. The reporting period for experienced physical violence was the past 12
      months and for morbidity symptoms, the past 14 days. MAIN RESULTS: Men aged 16-24
      years were significantly more likely to have experienced violence than women (OR
      = 3.2, 95% CI = 2.3 to 4.2). Female victims of physical violence were
      significantly more likely to rate their health as poor (OR = 2.02, 95% CI = 1.41
      to 2.89) and to report anxiety (OR = 2.14, 95% CI = 1.35 to 3.37), depression (OR
      = 2.36, 95% CI = 1.55 to 3.60), and stomach ache (OR = 1.58, 95% CI = 1.01 to
      2.47) than female non-victims. Male victims of physical violence were only
      significantly more likely to report stomach ache (OR = 1.73, 95% CI = 1.03 to
      2.89) than male non-victims. CONCLUSIONS: Associations between physical violence
      and poor self rated health and self reported morbidity were found to be
      significant for women, but not for men. It is probable that gender differences in
      experiences of violence, as well as gender differences in health related self
      perception, contribute to a gender specific process of victimisation. Improved
      knowledge about the relation between gender specific violence and victimisation
      as a gender specific consequence is essential for targeting violence prevention.

PMID- 14684731
TI  - Adverse pregnancy outcomes around incinerators and crematoriums.

PMID- 14684730
TI  - Neighbourhood deprivation and incidence of coronary heart disease: a multilevel
      study of 2.6 million women and men in Sweden.
AB  - STUDY OBJECTIVE: To examine whether neighbourhood deprivation predicts incidence
      rates of coronary heart disease, beyond age and individual income. DESIGN: Follow
      up study from 31 December 1995 to 31 December 1999. Women and men were analysed
      separately with respect to incidence rates of coronary heart disease. Multilevel
      logistic regression was used in the analysis with individual level
      characteristics (age, individual income) at the first level and level of
      neighbourhood deprivation at the second level. Neighbourhood deprivation was
      measured at small area market statistics level by the use of Care Need Index.
      SETTING: Sweden. PARTICIPANTS: All women and men aged 40-64 in the Swedish
      population, in total 2.6 million people. MAIN RESULTS: There was a strong
      relation between level of neighbourhood deprivation and incidence rates of
      coronary heart disease for both women and men. In the full model, which took
      account of individual income, the risk of developing coronary heart disease was
      87% higher for women and 42% higher for men in the most deprived neighbourhoods
      than in the most affluent neighbourhoods. For both women and men the variance at
      neighbourhood level was over twice the standard error, indicating significant
      differences in coronary heart disease risk between neighbourhoods. CONCLUSIONS:
      High levels of neighbourhood deprivation independently predict coronary heart
      disease for both women and men. Both individual and neighbourhood level
      approaches are important in health care policies.

PMID- 14684732
TI  - Characterization of a gene encoding two isoforms of a mitochondrial protein up
      regulated by cyclosporin A in activated T cells.
AB  - Cyclosporin A (CSA) is an immunosuppressor used in organ transplantation. A
      recent proteomic analysis has revealed that activation of T cells in the presence
      of CSA induces the synthesis of hundreds of new proteins. Here we used
      representational difference analysis to characterize some of the corresponding
      induced genes. After cDNA bank screening we focused on one of these genes, which
      we named CSA-conditional, T cell activation-dependent (CSTAD) gene. This gene
      produces two mRNAs resulting from alternative splicing events. They encode two
      proteins of 104 and 141 amino acids, CSTADp-S and CSTADp-L, for the short and
      long forms, respectively. FK506 had the same effect as CSA, whereas rapamycin did
      not affect the level of CSTAD gene expression, demonstrating that inhibition of
      the calcineurin activation pathway is involved in CSTAD gene up-regulation. CSA
      also led to overexpression of CSTAD in mice immunized in the presence of CSA,
      confirming the in vitro analysis. Microscopic and cytofluorimetric analysis of
      cells expressing green fluorescent protein-tagged CSTADp-L and CSTADp-S showed
      that both proteins colocalize with mitochondrial markers and depolarize the
      mitochondrial transmembrane potential without causing release of cytochrome c,
      apoptosis, or necrosis. Both CSTADp isoforms are sensitive to proteinase K,
      implying that they are located in the mitochondrial outer membrane. These data
      reveal a new mechanism of action for CSA, which involves up-regulation of a gene
      whose products are sorted to mitochondria and depolarize the mitochondrial
      membrane.

PMID- 14684733
TI  - High incidence of thymic epithelial tumors in E2F2 transgenic mice.
AB  - In virtually all human tumors, genetic and epigenetic alterations have been found
      which affect the INK4/-CYCLIN D/RB pathway, which regulates cell cycle entry and
      exit in normal cells. E2F transcription factors are important downstream
      components of this pathway, which act by controlling the expression of genes
      involved in DNA replication and cell cycle progression. To determine whether E2F2
      deregulation promotes proliferation and tumorigenesis in vivo, we generated E2F2
      transgenic mice, in which the Emu and murine pim1 promoter (pp) direct high
      expression of E2F2 in thymic epithelial cells. Emu-pp-E2F2 mice start to develop
      cytokeratin- and ER-TR4-positive cortical thymomas from the age of 20 weeks, and
      within 1 year, nearly all mice succumb to gross thymic epithelial tumors. General
      thymic morphology is largely maintained, but T cell development is perturbed in
      thymomas, with proportionately less CD4(+)CD8(+) double-positive thymocytes. In
      the first 3 months, E2F2 transgenic thymi exhibit only mild epithelial
      hyperplasia, and thereafter thymomas arise stochastically, probably following
      additional mutations. Interestingly, Emu-pp-E2F1 mice do not display cortical
      thymomas. These data argue that E2F2 promotes unscheduled cell division and
      oncogenic transformation of thymic epithelial cells.

PMID- 14684734
TI  - The crystal structure of placental growth factor in complex with domain 2 of
      vascular endothelial growth factor receptor-1.
AB  - Placental growth factor (PlGF) is a member of the vascular endothelial growth
      factor (VEGF) family and plays an important role in pathological angiogenic
      events. PlGF exerts its biological activities through binding to VEGFR1, a
      receptor tyrosine kinase that consists of seven immunoglobulin-like domains in
      its extracellular portion. Here we report the crystal structure of PlGF bound to
      the second immunoglobulin-like domain of VEGFR1 at 2.5 A resolution and compare
      the complex to the closely related structure of VEGF bound to the same receptor
      domain. The two growth factors, PlGF and VEGF, share a sequence identity of
      approximately 50%. Despite this moderate sequence conservation, they bind to the
      same binding interface of VEGFR1 in a very similar fashion, suggesting that both
      growth factors could induce very similar if not identical signaling events.

PMID- 14684735
TI  - Connective tissue growth factor (CCN2) induces adhesion of rat activated hepatic
      stellate cells by binding of its C-terminal domain to integrin alpha(v)beta(3)
      and heparan sulfate proteoglycan.
AB  - Connective tissue growth factor (CCN2, also known as CTGF) is a matricellular
      protein that appears to play an important role in hepatic stellate cell (HSC)
      mediated fibrogenesis. After signal peptide cleavage, the full-length CCN2
      molecule comprises four structural modules (CCN2(1-4)) and is susceptible to
      proteolysis by HSC yielding isoforms comprising essentially modules 3 and 4
      (CCN2(3-4)) or module 4 alone (CCN2(4)). In this study we show that rat activated
      HSC are capable of adhesion to all three CCN2 isoforms via the binding of module
      4 to integrin alpha(v)beta(3), a process that is dependent on interactions
      between module 4 and cell surface heparan sulfate proteoglycans (HSPGs). These
      findings are based on several lines of evidence. First, integrin alpha(v)beta(3)
      was detected in HSC lysates by immunoprecipitation and Western blot, and CCN2(4)
      mediated HSC adhesion was blocked by anti-integrin alpha(v)beta(3) antibody.
      Second, as assessed by immunoprecipitation and solid phase binding assay, CCN2(4)
      bound directly to integrin alpha(v)beta(3) in cell-free systems. Third,
      destruction or inhibition of synthesis of cell surface HSPGs with, respectively,
      heparinase or sodium chlorate abrogated HSC adhesion to CCN2(4). Fourth, prior
      occupancy of heparin-binding sites on CCN2(4) with soluble heparin completely
      blocked HSC adhesion. These findings indicate that integrin alpha(v)beta(3)
      functions as a co-receptor with HSPGs for CCN2(4)-mediated HSC adhesion.
      Furthermore, by peptide mapping and site-directed mutagenesis we demonstrated
      that the sequence IRTPKISKPIKFELSG within CCN2(4) is a unique binding domain for
      integrin alpha(v)beta(3) that is sufficient to mediate integrin alpha(v)beta(3)-
      and HSPG-dependent HSC adhesion. These findings offer the possibility of
      developing novel antifibrotic therapies that target the integrin-binding domain.

PMID- 14684736
TI  - Cyclin L2, a novel RNA polymerase II-associated cyclin, is involved in pre-mRNA
      splicing and induces apoptosis of human hepatocellular carcinoma cells.
AB  - We report the cloning and functional characterization of human cyclin L2, a novel
      member of the cyclin family. Human cyclin L2 shares significant homology to
      cyclin L1, K, T1, T2, and C, which are involved in transcriptional regulation via
      phosphorylation of the C-terminal domain of RNA polymerase II. The cyclin L2
      protein contains an N-terminal "cyclin box" and C-terminal dipeptide repeats of
      alternating arginines and serines, a hallmark of the SR family of splicing
      factors. A new isoform and the mouse homologue of human cyclin L2 have also been
      cloned in this study. Human cyclin L2 is expressed ubiquitously in normal human
      tissues and tumor cells. We show here that cyclin L2 co-localizes with splicing
      factors SC-35 and 9G8 within nuclear speckles and that it associates with
      hyperphosphorylated, but not hypophosphorylated, RNA polymerase II and CDK p110
      PITSLRE kinase via its N-terminal cyclin domains. It can also associate with the
      SC-35 and 9G8 through its RS repeat region. Recombinant cyclin L2 protein can
      stimulate in vitro mRNA splicing. Overexpression of human cyclin L2 suppresses
      the growth of human hepatocellular carcinoma SMMC 7721 cells both in vitro and in
      vivo, inducing cellular apoptosis. This process involves up-regulation of p53 and
      Bax and decreased expression of Bcl-2. The data suggest that cyclin L2 represents
      a new member of the cyclin family, which might regulate the transcription and RNA
      processing of certain apoptosis-related factors, resulting in tumor cell growth
      inhibition and apoptosis.

PMID- 14684737
TI  - Up-regulation of Bcl-2 homology 3 (BH3)-only proteins by E2F1 mediates apoptosis.
AB  - The E2F1 transcription factor is a critical downstream target of the tumor
      suppressor pRB. The retinoblastoma (RB) pathway is often inactivated in human
      tumors, resulting in deregulated E2F activity that can induce both proliferation
      and apoptosis. Bcl-2 homology 3 (BH3)-only proteins are pro-apoptotic members of
      the Bcl-2 protein family that trigger apoptosis in response to diverse stimuli.
      We show here that E2F1 up-regulates the expression of the pro-apoptotic BH3-only
      proteins PUMA, Noxa, Bim, and Hrk/DP5 through a direct transcriptional mechanism.
      Expression of the E7 protein of HPV16, which disrupts RB/E2F complexes, also up
      regulates the expression of these four BH3-only proteins, implicating endogenous
      E2F in this phenomenon. Indeed, endogenous E2F1 binds the promoters of these four
      genes. Furthermore, inhibition of E2F1-induced expression of either Noxa or PUMA
      results in a significant reduction in E2F1-induced apoptosis, indicating that
      increased Noxa and PUMA levels mediate this E2F1-induced apoptosis. Importantly,
      inhibition of E2F activity abolishes DNA damage-induced elevation of PUMA levels,
      implicating E2F in the physiological regulation of PUMA expression. These data
      provide a novel direct link between E2F and the apoptotic machinery and may
      explain the increased sensitivity of cells with a defective RB/E2F pathway to
      chemotherapy.

PMID- 14684738
TI  - Lecithin-retinol acyltransferase is essential for accumulation of all-trans
      retinyl esters in the eye and in the liver.
AB  - Lecithin-retinol acyltransferase (LRAT), an enzyme present mainly in the retinal
      pigmented epithelial cells and liver, converts all-trans-retinol into all-trans
      retinyl esters. In the retinal pigmented epithelium, LRAT plays a key role in the
      retinoid cycle, a two-cell recycling system that replenishes the 11-cis-retinal
      chromophore of rhodopsin and cone pigments. We disrupted mouse Lrat gene
      expression by targeted recombination and generated a homozygous Lrat knock-out
      (Lrat-/-) mouse. Despite the expression of LRAT in multiple tissues, the Lrat-/-
      mouse develops normally. The histological analysis and electron microscopy of the
      retina for 6-8-week-old Lrat-/- mice revealed that the rod outer segments are
      approximately 35% shorter than those of Lrat+/+ mice, whereas other neuronal
      layers appear normal. Lrat-/- mice have trace levels of all-trans-retinyl esters
      in the liver, lung, eye, and blood, whereas the circulating all-trans-retinol is
      reduced only slightly. Scotopic and photopic electroretinograms as well as
      pupillary constriction analyses revealed that rod and cone visual functions are
      severely attenuated at an early age. We conclude that Lrat-/- mice may serve as
      an animal model with early onset severe retinal dystrophy and severe retinyl
      ester deprivation.

PMID- 14684739
TI  - NEDL1, a novel ubiquitin-protein isopeptide ligase for dishevelled-1, targets
      mutant superoxide dismutase-1.
AB  - Approximately 20% of familial amyotrophic lateral sclerosis (FALS) arises from
      germ-line mutations in the superoxide dismutase-1 (SOD1) gene. However, the
      molecular mechanisms underlying the process have been elusive. Here, we show that
      a neuronal homologous to E6AP carboxyl terminus (HECT)-type ubiquitin-protein
      isopeptide ligase (NEDL1) physically binds translocon-associated protein-delta
      and also binds and ubiquitinates mutant (but not wild-type) SOD1 proportionately
      to the disease severity caused by that particular mutant. Immunohistochemically,
      NEDL1 is present in the central region of the Lewy body-like hyaline inclusions
      in the spinal cord ventral horn motor neurons of both FALS patients and mutant
      SOD1 transgenic mice. Two-hybrid screening for the physiological targets of NEDL1
      has identified Dishevelled-1, one of the key transducers in the Wnt signaling
      pathway. Mutant SOD1 also interacted with Dishevelled-1 in the presence of NEDL1
      and caused its dysfunction. Thus, our results suggest that an adverse interaction
      among misfolded SOD1, NEDL1, translocon-associated protein-delta, and Dishevelled
      1 forms a ubiquitinated protein complex that is included in potentially cytotoxic
      protein aggregates and that mutually affects their functions, leading to motor
      neuron death in FALS.

PMID- 14684740
TI  - Molecular characterization of the principal substrate binding site of the
      ubiquitous folding catalyst protein disulfide isomerase.
AB  - Disulfide bond formation in the endoplasmic reticulum of eukaryotes is catalyzed
      by the ubiquitously expressed enzyme protein disulfide isomerase (PDI). The
      effectiveness of PDI as a catalyst of native disulfide bond formation in folding
      polypeptides depends on the ability to catalyze disulfide-dithiol exchange, to
      bind non-native proteins, and to trigger conformational changes in the bound
      substrate, allowing access to buried cysteine residues. It is known that the b'
      domain of PDI provides the principal peptide binding site of PDI and that this
      domain is critical for catalysis of isomerization but not oxidation reactions in
      protein substrates. Here we use homology modeling to define more precisely the
      boundaries of the b' domain and show the existence of an intradomain linker
      between the b' and a' domains. We have expressed the recombinant b' domain thus
      defined; the stability and conformational properties of the recombinant product
      confirm the validity of the domain boundaries. We have modeled the tertiary
      structure of the b' domain and identified the primary substrate binding site
      within it. Mutations within this site, expressed both in the isolated domain and
      in full-length PDI, greatly reduce the binding affinity for small peptide
      substrates, with the greatest effect being I272W, a mutation that appears to have
      no structural effect.

PMID- 14684741
TI  - LIM kinase 1 activates cAMP-responsive element-binding protein during the
      neuronal differentiation of immortalized hippocampal progenitor cells.
AB  - LIM kinase 1 (LIMK1), a novel member of a subclass of the protein
      serine/threonine kinases, is known to play a role in the development and
      maintenance of neuronal circuits that mediate cognitive function. Genetic studies
      have implicated a mutation of LIMK1 as a causative factor in the impairment of
      visuospatial cognition in a neurodevelopmental disorder, Williams syndrome. A
      transcriptional factor, cAMP-responsive element-binding protein (CREB), is
      thought to be involved in the formation of many types of synaptic plasticity
      involving learning and memory. In the present study we show that the LIMK1
      activity is markedly induced during the differentiation of immortalized
      hippocampal progenitor (H19-7) cells. We found that the addition of neurogenic
      growth factor to H19-7 cells induces specific binding between LIMK1 and active
      CREB, that LIMK1 directly phosphorylates CREB, and that this leads to the
      stimulation of subsequent cAMP-responsive element-mediated gene transcription
      during H19-7 cell neuronal differentiation. In addition, we also found that LIMK1
      activation occurs through Rac/Cdc42- and p21-activated kinase-mediated signaling
      pathways. Moreover, when the plasmid encoding kinase-inactive LIMK1 was
      transfected to block the activation of endogenous LIMK1, the neuronal
      differentiation of H19-7 cells was significantly suppressed. These findings
      suggest that LIMK1 activation and subsequent CREB phosphorylation are important
      in the neuronal differentiation of central nervous system hippocampal progenitor
      cells.

PMID- 14684742
TI  - Formation of HLA-B27 homodimers and their relationship to assembly kinetics.
AB  - The human HLA-B27 class I molecule exhibits a strong association with the
      inflammatory arthritic disorder ankylosing spondylitis and other related
      arthropathies. Major histocompatibility complex class I heavy chains normally
      associate with beta(2)-microglobulin and peptide in the endoplasmic reticulum
      before transit to the cell surface. However, an unusual characteristic of HLA-B27
      is its ability to form heavy chain homodimers through an unpaired cysteine at
      position 67 in the peptide groove. Homodimers have previously been detected
      within the ER and at the cell surface, but their mechanism of formation and role
      in disease remain undefined. Here we demonstrate, in the rat C58 thymoma cell
      line and in human HeLa cells transfected with HLA-B27, that homodimer formation
      involves not only cysteine at position 67 but also the conserved structural
      cysteine at position 164. We also show that homodimer formation can be induced in
      the non-disease-associated HLA class I allele HLA-A2 by slowing its assembly rate
      by incubation of cells at 26 degrees C, suggesting that homodimer formation in
      the endoplasmic reticulum may occur as a result of the slower folding kinetics of
      HLA-B27. Finally, we report an association between unfolded HLA-B27 molecules and
      immunoglobulin-binding protein at the cell surface.

PMID- 14684743
TI  - The type 1 phosphatase Reg1p-Glc7p is required for the glucose-induced
      degradation of fructose-1,6-bisphosphatase in the vacuole.
AB  - Protein phosphatases play an important role in vesicular trafficking and membrane
      fusion processes. The type 1 phosphatase Glc7p and its regulatory subunit Reg1p
      were identified as required components in the glucose-induced targeting of the
      key gluconeogenic enzyme fructose-1,6-bisphosphatase (FBPase) to the vacuole for
      degradation. The interaction of Reg1p with Glc7p was important for the transport
      of FBPase from intermediate vacuole import and degradation (Vid) vesicles to
      vacuoles. The glc7-T152K mutant strain exhibited a reduced Reg1p binding along
      with defects in FBPase degradation and Vid vesicle trafficking to the vacuole. In
      this mutant, Vid vesicles were the most defective components, whereas the vacuole
      was also defective. Shp1p and Glc8p regulate Glc7p phosphatase activity and are
      required for FBPase degradation. In the Deltashp1 and Deltaglc8 strains, Reg1p
      Glc7p interaction was not affected, suggesting that phosphatase activity is also
      necessary for FBPase degradation. Similar to those seen in the glc7-T152K mutant,
      the Deltashp1 and Deltaglc8 mutants exhibited severely defective Vid vesicles,
      but partially defective vacuoles. Taken together, our results suggest that Reg1p
      Glc7p interaction and Glc7p phosphatase activity play a required role in the Vid
      vesicle to vacuole-trafficking step along the FBPase degradation pathway.

PMID- 14684744
TI  - Dioxin increases C/EBPbeta transcription by activating cAMP/protein kinase A.
AB  - The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD = dioxin)
      has been shown to increase the expression of C/EBPbeta. The modulated expression
      of C/EBPbeta has been suggested to be associated with toxic responses of TCDD
      such as wasting syndrome, diabetes, and inhibition of adipocyte differentiation.
      This study focused on the regulatory mechanism of TCDD-mediated transcriptional
      activation of C/EBPbeta. Elevated C/EBPbeta mRNA and protein levels in mouse
      embryonic fibroblasts (C3H10T(1/2)) and in mouse hepatoma cells (Hepa1c1c7) were
      correlated with increased binding affinity of the C/EBPbeta protein. Transfection
      studies with different deletion constructs of the CCAAT/enhancer-binding protein
      promoter indicated that a small region located 60-120 bp upstream of the start
      site of transcription is required for activation of the C/EBPbeta gene by TCDD in
      both cell lines tested. Further analysis using mutation constructs of the
      C/EBPbeta promoter demonstrated that activation of the C/EBPbeta promoter is
      mediated through incomplete cAMP-response element-binding protein (CREB) sites
      located close to the TATA box of the C/EBPbeta gene. The protein kinase A (PKA)
      inhibitor H89 completely blocks the TCDD-dependent effect on C/EBPbeta promoter
      activity, indicating that TCDD activates CREB binding via a cAMP/PKA pathway,
      which is supported by the increased cAMP level and PKA activity observed after
      TCDD treatment. Gel shift analyses demonstrated that CREB itself binds to the
      putative CREB motif that mediates the TCDD-dependent effect on C/EBPbeta gene
      transcription. Cotransfection experiments with CREB and PKA expression plasmids
      further supported our conclusions that the TCDD-dependent effect on C/EBPbeta
      transcription is mediated via PKA-dependent CREB activation.

PMID- 14684745
TI  - The HECT domain ligase itch ubiquitinates endophilin and localizes to the trans
      Golgi network and endosomal system.
AB  - Endophilin A1 is an SH3 domain-containing protein functioning in membrane
      trafficking on the endocytic pathway. We have identified the E3 ubiquitin ligase
      itch/AIP4 as an endophilin A1-binding partner. Itch belongs to the Nedd4/Rsp5p
      family of proteins and contains an N-terminal C2 domain, four WW domains and a
      catalytic HECT domain. Unlike other Nedd4/Rsp5p family members, itch possesses a
      short proline-rich domain that mediates its binding to the SH3 domain of
      endophilin A1. Itch ubiquitinates endophilin A1 and the SH3/proline-rich domain
      interaction facilitates this activity. Interestingly, itch co-localizes with
      markers of the endosomal system in a C2 domain-dependent manner and upon EGF
      stimulation, endophilin A1 translocates to an EGF-positive endosomal compartment
      where it colocalizes with itch. Moreover, EGF treatment of cells stimulates
      endophilin A1 ubiquitination. We have thus identified endophilin A1 as a
      substrate for the endosome-localized ubiquitin ligase itch. This interaction may
      be involved in ubiquitin-mediated sorting mechanisms operating at the level of
      endosomes.

PMID- 14684746
TI  - Identification of phosphorylation sites on the yeast ribonucleotide reductase
      inhibitor Sml1.
AB  - Sml1 is a small protein in Saccharomyces cerevisiae which inhibits the activity
      of ribonucleotide reductase (RNR). RNR catalyzes the rate-limiting step of de
      novo dNTP synthesis. Sml1 is a downstream effector of the Mec1/Rad53 cell cycle
      checkpoint pathway. The phosphorylation by Dun1 kinase during S phase or in
      response to DNA damage leads to diminished levels of Sml1. Removal of Sml1
      increases the population of active RNR, which raises cellular dNTP levels. In
      this study using mass spectrometry and site-directed mutagenesis, we have
      identified the region of Sml1 phosphorylation to be between residues 52 and 64
      containing the sequence GSSASASASSLEM. This is the first identification of a
      phosphorylation sequence of a Dun1 biological substrate. This sequence is quite
      different from the consensus Dun1 phosphorylation sequence reported previously
      from peptide library studies. The specific phosphoserines were identified to be
      Ser(56), Ser(58), and Ser(60) by chemical modification of these residues to S
      ethylcysteines followed by collision activated dissociation. To investigate
      further Sml1 phosphorylation, we constructed the single mutants S56A, S58A, S60A,
      and the triple mutant S56A/S58A/S60A and compared their degrees of
      phosphorylation with that of wild type Sml1. We observed a 90% decrease in the
      relative phosphorylation of S60A compared with that of wild type, a 25% decrease
      in S58A, and little or no decrease in the S56A mutant. There was no observed
      phosphate incorporation in the triple mutant, suggesting that Ser(56), Ser(58),
      and Ser(60) in Sml1 are the sites of phosphorylation. Further mutagenesis studies
      reveal that Dun1 kinase requires an acidic residue at the +3 position, and there
      is cooperativity between the phosphorylation sites. These results show that Dun1
      has a unique phosphorylation motif.

PMID- 14684747
TI  - The structure of the 1L-myo-inositol-1-phosphate synthase-NAD+-2-deoxy-D-glucitol
      6-(E)-vinylhomophosphonate complex demands a revision of the enzyme mechanism.
AB  - 1l-myo-inositol 1-phosphate (MIP) synthase catalyzes the conversion of d-glucose
      6-phosphate to 1l-myo-inositol 1-phosphate, the first and rate-limiting step in
      the biosynthesis of all inositol-containing compounds. It involves an oxidation,
      enolization, intramolecular aldol cyclization, and reduction. Here we present the
      structure of MIP synthase in complex with NAD(+) and a high-affinity inhibitor, 2
      deoxy-d-glucitol 6-(E)-vinylhomophosphonate. This structure reveals interactions
      between the enzyme active site residues and the inhibitor that are significantly
      different from that proposed for 2-deoxy-d-glucitol 6-phosphate in the previously
      published structure of MIP synthase-NAD(+)-2-deoxy-d-glucitol 6-phosphate. There
      are several other conformational changes in NAD(+) and the enzyme active site as
      well. Based on the new structural data, we propose a new and completely different
      mechanism for MIP synthase.

PMID- 14684748
TI  - Identification of novel nuclear export and nuclear localization-related signals
      in human heat shock cognate protein 70.
AB  - Heat shock cognate protein 70 (Hsc70) serves nuclear transport of several
      proteins as a molecular chaperone. We have recently identified a novel variant of
      human Hsc70, heat shock cognate protein 54 (Hsc54), that lacks amino acid
      residues 464-616 in the protein binding and variable domains of Hsc70. In the
      present study, we examined nucleocytoplasmic localization of Hsc70 and Hsc54 by
      using green fluorescent protein (GFP) fusions. GFP-Hsc70 is localized in both the
      cytoplasm and the nucleus at 37 degrees C and accumulated into the
      nucleolus/nucleus after heat shock, whereas GFP-Hsc54 always remained exclusively
      in the cytoplasm under these conditions. Mutation studies indicated that 20 amino
      acid residues of nuclear localization-related signals, which are missing in Hsc54
      but are retained in Hsc70, are required for proper nuclear localization of Hsc70.
      We further found that Hsc54 contains a functional leucine-rich nuclear export
      signal (NES, (394)LDVTPLSL(401)) which is differently situated from the
      previously proposed NES in Saccharomyces cerevisiae Ssb1p. The cytoplasmic
      localization of Hsc54 was impaired by a mutation in NES as well as by a nuclear
      export inhibitor, leptomycin B, suggesting that Hsc54 is actively exported from
      the nucleus to the cytoplasm through a CRM1-dependent mechanism. In contrast, the
      nucleocytoplasmic localization of Hsc70 was not affected by the same mutation of
      NES or leptomycin B. These results suggest that the nuclear localization-related
      signal could functionally mask NES leading to prolonged retention of Hsc70 in the
      nucleus. An additional mechanism for unmasking the NES may regulate
      nucleocytoplasmic trafficking of Hsc70.

PMID- 14684749
TI  - Increased myeloproliferation in glutathione S-transferase pi-deficient mice is
      associated with a deregulation of JNK and Janus kinase/STAT pathways.
AB  - It has been shown that glutathione S-transferase pi (GSTpi) interacts with and
      suppresses the activity of c-Jun NH(2)-terminal kinase (JNK). GST-deficient mice
      (GSTpi(-/-)) have higher levels of circulating white blood cells, with similar
      proportions of lymphocytes, monocytes, and granulocytes. Interestingly, a
      selective expansion of splenic B lymphocytes was observed in GSTpi(-/-) animals
      but no change in T lymphocytes or natural killer cells. A peptidomimetic
      inhibitor of GSTpi that disrupts the interaction between GSTpi and JNK mimics in
      wild type mice the increased myeloproliferation observed in GSTpi(-/-) animals.
      Until now, the molecular basis for this effect has not been defined. In an in
      vitro hematopoiesis assay, interleukin-3, granulocyte colony-stimulating factor,
      and granulocyte/macrophage colony-stimulating factor were more effective at
      stimulating proliferation of hematopoietic cells in GSTpi(-/-) mice than in wild
      type. The JNK inhibitor SP600125 which caused little inhibition of cytokine
      induced myeloproliferation in wild type mice, decreased the number of colonies in
      GSTpi(-/-) animals. A more sustained phosphorylation of the STAT family of
      proteins was also observed in GSTpi(-/-) bone marrow-derived mast cells exposed
      to interleukin-3. This was associated with an increased proliferation and a down
      regulation of expression of negative regulators of the Janus kinase-STAT pathway
      SHP, Src homology 2 domain-containing tyrosine phosphatase-1 and -2. The
      increased activation of JNK and STATs in GSTpi-deficient mice provides a viable
      mechanism for the increased myeloproliferation in these animals. These data also
      confirm the important role that GSTpi plays in the regulation of cell signaling
      pathways in a myeloproliferative setting.

PMID- 14684750
TI  - Trihydrophobin 1 is a new negative regulator of A-Raf kinase.
AB  - Our previous work indicated that instead of binding to B-Raf or C-Raf,
      trihydrophobin 1 (TH1) specifically binds to A-Raf kinase both in vitro and in
      vivo. In this work, we investigated its function further. Using confocal
      microscopy, we found that TH1 colocalizes with A-Raf, which confirms our former
      results. The region of TH1 responsible for the interaction with A-Raf is mapped
      to amino acids 1-372. Coimmunoprecipitation experiments demonstrate that TH1 is
      associated with A-Raf in both quiescent and serum-stimulated cells. Wild type A
      Raf binds increasingly to TH1 when it is activated by serum and/or upstream
      oncogenic Ras/Src compared with that of "kinase-dead" A-Raf. The latter can still
      bind to TH1 under the same experimental condition. The binding pattern of A-Raf
      implies that this interaction is mediated in part by the A-Raf kinase activity.
      As indicated by Raf protein kinase assays, TH1 inhibits A-Raf kinase, whereas
      neither B-Raf nor C-Raf kinase activity is influenced. Furthermore, we observed
      that TH1 inhibited cell cycle progression in TH1 stably transfected 7721 cells
      compared with mock cells, and flow cell cytometry analysis suggested that the TH1
      stably transfected 7721 cells were G(0)/G(1) phase-arrested. Taken together, our
      data provide a clue to understanding the cellular function of TH1 on Raf isoform
      specific regulation.

PMID- 14684751
TI  - The farnesoid X receptor controls gene expression in a ligand- and promoter
      selective fashion.
AB  - Farnesoid X receptor (FXR) is a nuclear receptor for bile acids. Ligand activated
      FXR regulates transcription of genes to allow feedback control of bile acid
      synthesis and secretion. There are five major bile acids in humans. We have
      previously demonstrated that lithocholate acts as an FXR antagonist, and here we
      show that the other four bile acids, chenodeoxycholate (CDCA), deoxycholate
      (DCA), cholate (CA), and ursodeoxycholate (UDCA), act as selective FXR agonists
      in a gene-specific fashion. In an in vitro coactivator association assay, CDCA
      fully activated FXR, whereas CA partially activated FXR and DCA and UDCA had
      negligible activities. Similar results were also obtained from a glutathione S
      transferase pull-down assay in which only CDCA and the synthetic FXR agonist
      GW4064 significantly increased the interaction of SRC-1 with FXR. In FXR
      transactivation assays with a bile salt export pump (BSEP) promoter-driven
      luciferase construct, bile acids showed distinct abilities to activate the BSEP
      promoter: CDCA, DCA, CA, and UDCA increased luciferase activity by 25-, 20-, 18-,
      and 8-fold, respectively. Consistently, CDCA increased BSEP mRNA by 750-fold in
      HepG2 cells, whereas DCA, CA, and UDCA induced BSEP mRNA by 250-, 75-, and 15
      fold, respectively. Despite the partial induction of BSEP mRNA, CA, DCA, and UDCA
      effectively repressed expression of cholesterol 7alpha-hydroxylase, another FXR
      target. We further showed that all four bile acids significantly increased FXR
      protein, suggesting the existence of an auto-regulatory loop in FXR signaling
      pathways. In conclusion, these results suggest that the binding of each bile acid
      results in a different FXR conformations, which in turn differentially regulates
      expression of individual FXR targets.

PMID- 14684752
TI  - Regulation of interleukin receptor-associated kinase (IRAK) phosphorylation and
      signaling by iota protein kinase C.
AB  - We have previously shown that the activity of the interleukin-1 (IL-1) receptor
      associated kinase (IRAK) is required for nerve growth factor (NGF)-induced
      activation of NF-kappaB and cell survival ((2002) J. Biol. Chem. 277, 28010
      28018). Herein we demonstrate that NGF induces co-association of IRAK with
      atypical protein kinase C iota (PKC) and that the iota PKC.IRAK complex is
      recruited to the p75 neurotrophin receptor. Recruitment of IRAK to the receptor
      was dependent upon the activity of the iota PKC. Moreover, transfection of kinase
      dead iota PKC blocked both NGF- and IL-1-induced IRAK activation and the activity
      of NF-kappaB. Hence, iota PKC lies upstream of IRAK in the kappaB pathway.
      Examining the primary structure of IRAK, we identified three putative PKC
      phosphorylation sites; iota PKC selectively phosphorylated peptide 1 (RTAS)
      within the death domain domain at Thr66, which is highly conserved among all IRAK
      family members. Mutation of Thr66 to Ala impaired the autokinase activity of IRAK
      and reduced its association with iota PKC but not TRAF6, resulting in impaired
      NGF- as well as IL-1-induced NF-kappaB activation. These findings provide insight
      into the underlying mechanism whereby IRAK regulates the kappaB pathway and
      reveal that IRAK is a substrate of iota PKC.

PMID- 14684753
TI  - Insulin clearance in obesity.
AB  - Insulin uptake and degradation is a complex and not yet completely understood
      process involving not only insulin sensitive tissues. The most important
      degradative system is insulin degrading enzyme which is a highly conserved
      metalloendopeptidase requiring Zn(++) for its proteolytic action, although
      protein disulfide isomerase and cathepsin D are also involved in insulin
      metabolism. The liver and the kidney are the principal sites for insulin
      clearance. In obese subjects with hyperinsulinemia and high levels of free fatty
      acids, insulin hepatic clearance is impaired, while the glomerular filtration
      rate, renal plasma flow and albumin excretion are increased, suggesting a state
      of renal vasodilatation leading to an abnormally transmitted arterial pressure to
      the glomerular capillaries through a dilated afferent arteriole. Insulin can be
      cleared also by muscle, adipocytes, gastrointestinal cells, fibroblasts,
      monocytes and lymphocytes which contain insulin receptors and internalization and
      regulation mechanism for insulin metabolism.

PMID- 14684754
TI  - The effect of flax seed cultivars with differing content of alpha-linolenic acid
      and lignans on responses to mental stress.
AB  - BACKGROUND: Phytoestrogens offer a possible alternative to hormone replacement
      therapy. Flax seed contains large quantities of a phytoestrogen precursor,
      secoisolariciresinol diglucoside (SDG), as well as large quantities of alpha
      linolenic acid; these factors may be protective against vascular disease. We have
      previously shown that the rise in blood pressure during mental stress is a strong
      predictor of atherosclerosis progression. METHODS: 35 postmenopausal women with
      vascular disease, 62 +/- 8 years of age, were treated in a random-sequence double
      blind Latin square crossover study comparing three strains of flax seed: Flanders
      (low in lignan and high in alpha-linolenic acid), Linola 989 (high in lignan and
      low in alpha-linolenic acid) and AC Linora (intermediate in both lignan and alpha
      linolenic acid). RESULTS: Compared to the pre-treatment baseline diet, all three
      strains of flax significantly reduced blood pressure during mental stress induced
      by a frustrating cognitive task (Stroop color-word interference task) (p =
      0.004). Linola 989, the strain highest in lignan and lowest in alpha-linolenic
      acid, was associated with the least increase in peripheral resistance during
      stress, the greatest reduction in plasma cortisol during stress and the smallest
      increase in plasma fibrinogen during mental stress. CONCLUSION: Flax
      phytoestrogens ameliorate certain responses to stress and thus may afford
      protection against atherosclerosis; this hypothesis should be tested in clinical
      trials.

PMID- 14684755
TI  - Involvement of CYP 2C9 in mediating the proinflammatory effects of linoleic acid
      in vascular endothelial cells.
AB  - OBJECTIVE: Polyunsaturated fatty acids such as linoleic acid are well known
      dietary lipids that may be atherogenic by activating vascular endothelial cells.
      In the liver, fatty acids can be metabolized by cytochrome P450 (CYP) enzymes,
      but little is known about the role of these enzymes in the vascular endothelium.
      CYP 2C9 is involved in linoleic acid epoxygenation, and the major product of this
      reaction is leukotoxin (LTX). We investigated the role of CYP-mediated mechanisms
      of linoleic acid metabolism in endothelial cell activation by examining the
      effects of linoleic acid or its oxidized metabolites such as LTX and leukotoxin
      diol (LTD). METHODS: The effect of linoleic acid on CYP 2C9 gene expression was
      studied by RT-PCR. Oxidative stress was monitored by measuring DCF fluorescence
      and intracellular glutathione levels, and electrophoretic mobility shift assay
      was carried out to study the activation of oxidative stress sensitive
      transcription factors. Analysis of oxidized lipids was carried out by liquid
      chromatography/mass spectrometry. RESULTS: Linoleic acid treatment for six hours
      increased the expression of CYP 2C9 in endothelial cells. Linoleic acid-mediated
      increase in oxidative stress and activation of AP-1 were blocked by
      sulfaphenazole, a specific inhibitor of CYP 2C9. The linoleic acid metabolites
      LTX and LTD increased oxidative stress and activation of transcription factors
      only at high concentrations. CONCLUSION: Our data show that CYP 2C9 plays a key
      role in linoleic acid-induced oxidative stress and subsequent proinflammatory
      events in vascular endothelial cells by possibly causing superoxide generation
      through uncoupling processes.

PMID- 14684756
TI  - Effect of triglyceride structure on fecal excretion of 13C-labeled triglycerides.
AB  - OBJECTIVE: The aim of this work was to determine the effects of specific changes
      in the structure of (13)C-labeled triglyceride (TG*) on its fecal excretion
      relative to total stool fat excretion determined simultaneously in patients with
      reduced exocrine pancreatic function. METHODS: A series of 47 studies were
      conducted in 26 young cystic fibrosis (CF) patients and 11 adult patients with
      chronic pancreatitis over a five year period. Each test consisted of ingesting a
      single high fat test meal containing both (13)C-labeled triglyceride (TG*) and
      dysprosium chloride (DyCl(3)) a nonabsorbable marker of intestinal transit; in
      most studies the food colorant brilliant blue (FD&C blue #1) was administered
      along with the DyCl(3). The TG*s tested were: P*P*P* = TRIPALMITIN-1,1,1
      (13)C(3); SO*S = 2-OCTANOYL-1,3-DISTEARIN-2-octanoyl-1,2-(13)C(2); and P*LP* = 2
      LAURYL-1,3-DIPALMITIN-dipalmitoyl-1,1,2,2-(13)C(4). Ingestion of the test meal
      was followed by collection of individual stools for at least 72 hours. Stools
      were analyzed for (13)C-Excess ((13)C*), total fat, and Dy. RESULTS: Excretion of
      P*LP* showed a high degree of linear correlation with stool fat (r(2) = 0.924)
      over a wide-range of fecal fat values. Excretion of SO*S was also significantly
      correlated with stool fat, but its excretion was less than 10% at all levels of
      steatorrhea and the slope of the regression line relating TG* excretion to stool
      fat was some four to five times smaller than observed for P*LP*. Fecal excretion
      of P*P*P* was highly correlated with stool fat (r(2) = 0.941) in patients with
      moderate steatorrhea (<25 g fat/24 hours) and the slope of the regression line
      (3.20) was considerably greater than for P*LP*. Only results from those studies
      in which stool collections were complete (Dy excretion >90%) were utilized in the
      statistical comparisons (36 of 47 studies). CONCLUSIONS: The observed highly
      significant linear correlation between P*LP* and stool fat over the entire range
      of steatorrhea suggests that P*LP* excretion may be a suitable surrogate for
      fecal fat in patients with reduced exocrine pancreatic function. Because fecal
      excretion of TG* administered as described can be accurately determined by
      sampling only two visually marked stools, development of a noninvasive test to
      replace the current 72-hour stool fat test using this approach is possible. Use
      of other engineered TG*s and/or labeled fatty acids, may provide a method for non
      invasive in vivo assessment of the specific defect(s) leading to steatorrhea in
      other patient groups.

PMID- 14684757
TI  - Orange juice ingestion and supplemental vitamin C are equally effective at
      reducing plasma lipid peroxidation in healthy adult women.
AB  - OBJECTIVE: To directly examine the contribution of vitamin C to the antioxidant
      potential of fruits and vegetables, the antioxidant effect of orange juice
      consumption (8 and 16 fl. oz.) was compared to the antioxidant effect of
      supplemental vitamin C (dosage equivalent to that supplied by 8 fl. oz. of orange
      juice). METHODS: Subjects (n = 11; 28.6 +/- 2.1 years) received each treatment in
      a 3 x 3 randomized crossover design, and each two-week treatment was preceded by
      a two-week washout. During the entire trial, subjects restricted fruit and
      vegetable consumption to < or =3 servings per day except the vitamin C-rich foods
      (items containing >20 mg/serving), which were restricted to < or =3 servings per
      week. A fasting blood sample was collected at the end of each washout and each
      treatment period. RESULTS: Following washouts, plasma vitamin C and lipid
      peroxidation (plasma TBARS) were similar by treatment group and averaged 25.4 +/-
      3.6 micromol/L and 3.82 +/- 0.10 nmol/mL respectively. Plasma vitamin C
      concentrations were similar following each treatment period, 37.9 +/- 8.1, 45.8
      +/- 9.4, and 38.3 +/- 12.4 micromol/L for the 8 and 16 fl. oz. orange juice
      treatments and the supplement treatment, respectively. All intervention
      treatments reduced plasma TBARS as compared to pretreatment values: -47% (p =
      0.013), -40% (p = 0.083), and -46% (p = 0.015) for the 8 and 16 fl. oz. orange
      juice treatments and supplement treatment respectively. CONCLUSIONS: These data
      indicate that the regular consumption of 8 fl. oz. orange juice or supplemental
      vitamin C ( approximately 70 mg/day) effectively reduced a marker of lipid
      peroxidation in plasma.

PMID- 14684758
TI  - Null and opposing effects of Asian ginseng (Panax ginseng C.A. Meyer) on acute
      glycemia: results of two acute dose escalation studies.
AB  - OBJECTIVE: We have repeatedly reported that a batch of American ginseng with a
      specific ginsenoside (glycosidal saponin) profile decreases acute postprandial
      glycemia. We investigated whether Asian ginseng is able to replicate this
      glycemia-lowering efficacy in two separate acute dose escalation studies.
      METHODS: Each study was conducted in a separate sample of 11 healthy subjects
      (gender: 8M:3F and 6M:5F, age: 29 +/- 2y and 27 +/- 3y, BMI: 28.5 +/- 2.1 kg/m(2)
      and 26.9 +/- 1.4 kg/m(2)) using a randomized, single-blind, placebo-controlled,
      multiple-crossover design. Treatments consisted of 0 (placebo), 1, 2, and 3 g of
      Asian ginseng for the first study and 0 (placebo), 3, 6, and 9 g Asian ginseng
      for the second study administered 40 minutes before a 75g-OGTT protocol with
      blood drawn at -40, 0, 15, 30, 45, 60, 90, and 120 minutes. Ginsenosides were
      analyzed by HPLC-UV. RESULTS: Neither the main effect of pooled-treatment, nor
      dose, nor either factors interaction with time was significant for incremental
      plasma glucose and insulin. But the diagnostically and therapeutically relevant
      two-hour plasma glucose (2h-PG) value was significantly higher for pooled Asian
      ginseng treatment than placebo (5.46 +/- 0.31 versus 4.99 +/- 0.30 mmol/L, p =
      0.050). Ginsenoside analyses showed that the Asian ginseng contained up to 96%
      lower and sevenfold higher quantities of various ginsenosides and their ratios
      than our previous efficacious batch of American ginseng. CONCLUSIONS: Asian
      ginseng showed both null and opposing effects on indices of acute postprandial
      plasma glucose and insulin. This is in contrast to our findings with American
      ginseng. One explanation may be the marked ginsenoside differences. Practitioners
      and consumers should be aware of ginseng's variable effects.

PMID- 14684759
TI  - The association between magnesium intake and fasting insulin concentration in
      healthy middle-aged women.
AB  - OBJECTIVE: We assessed the association between magnesium intake and fasting
      insulin levels in a large cohort of women. METHODS: Female nurses free of
      diabetes, cardiovascular diseases and cancer from the Nurses Health Study
      provided blood samples between 1989-1990. We selected a sub-sample of 219 women
      for this analysis. Magnesium intake was assessed by a food frequency
      questionnaire in 1990 and categorized into quartiles. Cross-sectional geometric
      means of fasting insulin concentrations by quartiles of magnesium intake were
      obtained with Generalized Linear Model and adjusted for several risk factors and
      lifestyle characteristics. RESULTS: After adjustment for age, body mass index
      (BMI), total energy, physical activity, hours per week spent sitting outside
      work, alcohol intake, smoking, and family history of diabetes, magnesium intake
      was inversely associated with fasting insulin concentration. The multivariate
      adjusted geometric mean for women in the lowest quartile of magnesium intake was
      11.0 microU/mL and 9.3 microU/mL among those in the highest quartile of magnesium
      intake (p for trend = 0.04). The inverse association remained when we considered
      magnesium from only food sources. CONCLUSION: Higher magnesium intake is
      associated with lower fasting insulin concentrations among women without
      diabetes. Because lower fasting insulin concentrations generally reflect greater
      insulin sensitivity, these findings provide a mechanism through which higher
      dietary magnesium intake may reduce the risk of developing type 2 diabetes
      mellitus.

PMID- 14684760
TI  - Food away from home, sugar-sweetened drink consumption and juvenile obesity.
AB  - OBJECTIVE: To identify if particular foods or food groups may be associated with
      obesity in children and adolescents and to determine if consuming food away from
      home (FAFH) has an effect on the nutritional quality of their diets. DESIGN: One
      year cross-sectional study. SETTING/SUBJECTS: The obese subjects (n = 91) were on
      the waiting list for a hospital-based weight control treatment program. The non
      obese subjects (n = 90) were recruited from community advertisements. MEASURES OF
      OUTCOME: Information on food intake was obtained using the dietary history method
      by a Registered Dietitian. Body fat was determined by bioelectrical impedance
      analysis. RESULTS: Obese children and adolescents consumed significantly more
      servings of meat and alternatives, grain products, FAFH, sugar-sweetened drinks
      and potato chips which contributed to a higher calorie, fat and sugar intake
      compared to non-obese children and adolescents. Sugar-sweetened drinks were only
      significantly greater in boys. The consumption of meat servings, sugar-sweetened
      drinks and FAFH was positively correlated with percent body fat. The frequency of
      food consumed outside of the Canada's Food Guide To Healthy Eating was not
      different between the two groups. CONCLUSIONS: Obese children and adolescents
      need to limit their access to food consumed away from home and sugar-sweetened
      drinks as there is a relationship between these foods and body fatness.

PMID- 14684761
TI  - Body cell mass measured by total body potassium in normal-weight and obese men
      and women.
AB  - OBJECTIVE: Total body potassium (TBK) concentration is linearly correlated with
      the size of the body cell mass (BCM). The aim of this study was to compare BCM in
      normal-weight and obese individuals. METHODS: 271 individuals (207 males, 64
      females), 20 to 67 years of age, participated in this study. Subjects were
      separated by body mass index (BMI): BMI < 25 kg/m(2) (BMI-L) and BMI > 25 kg/m(2)
      (BMI-H). (40)K was assessed using a whole-body counter and BCM was calculated.
      RESULTS: BCM and TBK were significantly greater in men, with a trend to be
      greater in women in BMI-H compared to men in BMI-L. TBK/body weight was
      significantly lower, while TBK/height was significantly greater for men and women
      in BMI-H compared to men and women in BMI-L. Fat-free mass (FFM) was
      significantly greater for men in BMI-H, with no significant differences in FFM
      between the two groups of women. CONCLUSIONS: The healthy obese subjects in the
      present study had a greater BCM than the non-obese subjects. These results
      indicate that it is important to assess BCM in obese individuals because it could
      influence the type of weight loss regimen that will be used in order to preserve
      BCM.

PMID- 14684762
TI  - Effect of flaxseed and wheat bran on serum hormones and lignan excretion in
      premenopausal women.
AB  - OBJECTIVE: To examine the effects of flaxseed consumption (a lignan-rich plant
      food) alone and in combination with wheat bran on serum hormones and urinary
      lignan excretion in premenopausal women. METHODS: Sixteen subjects were studied
      for four feeding treatments lasting two menstrual cycles each in a randomized,
      crossover design. During each treatment, subjects consumed their habitual diets
      supplemented with baked goods containing no flaxseed or wheat bran, 10 g of
      flaxseed, 28 g of wheat bran, or 10 g of flaxseed plus 28 g of wheat bran/day.
      Serum samples collected during the mid-luteal phase of the second menstrual cycle
      of each diet treatment were analyzed for serum hormones and sex hormone binding
      globulin. Urine samples collected during the same time period were analyzed for
      urinary lignan excretion. RESULTS: There were no changes in serum hormone
      concentrations or sex hormone binding globulin on any of the treatments. Urinary
      lignan excretion significantly increased on diet treatments that included
      flaxseed, but inclusion of wheat bran did not significantly alter lignan
      excretion. CONCLUSIONS: Urinary lignan excretion increased with flaxseed
      consumption, but serum hormones did not change in this group of premenopausal
      women. Consumption of wheat bran with flaxseed did not alter urinary lignan
      excretion associated with flaxseed consumption.

PMID- 14684763
TI  - Dietary treatment of hypercholesterolemia: can we predict long-term success?
AB  - OBJECTIVE: To look for associations between changes in LDL cholesterol and
      baseline characteristics of patients receiving dietary therapy for
      hypercholesterolemia. METHODS: Ninety-six hypercholesterolemic individuals aged
      30-65 from three primary care clinics and a worksite clinic received counseling
      by a physician and/or a dietitian for lifestyle and dietary modifications.
      Baseline nutritional intake was evaluated using three-day food diaries.
      Lipoprotein levels were evaluated at six weeks and thereafter every three months
      for one year. Partial (adjusted) correlations (beta) were calculated between
      baseline parameters (demographic, anthropometric, nutritional and laboratory) and
      changes of LDL cholesterol for the short and long term (three and 12 months).
      RESULTS: The average LDL cholesterol level decreased by 6 +/- 10% (p < 0.001) at
      the end of 12 months. This reduction was positively correlated with baseline LDL
      cholesterol level (beta = +0.4, p = 0.001), and negatively correlated with the
      baseline BMI (beta = -0.2, p < 0.05) and saturated fat intake (beta = -0.3, p <
      0.05). The differences between low and high subgroups of baseline LDL
      cholesterol, BMI and saturated fat intake became apparent only after six to
      twelve months of therapy and probably result from varying levels of adherence to
      the dietary regimen. A significant correlation was found between the change in
      LDL cholesterol after six weeks and the change in LDL cholesterol after 12 months
      (beta = 0.4, p < 0.001). CONCLUSIONS: The probability of successfully reducing
      LDL cholesterol with dietary therapy can be predicted by baseline LDL cholesterol
      level, BMI and saturated fat intake, as well as by the response to dietary
      changes within six weeks of therapy.

PMID- 14684765
TI  - Editorial comment--with or without protection? The second important question in
      carotid artery stenting.

PMID- 14684767
TI  - Preventive antibacterial treatment improves the general medical and neurological
      outcome in a mouse model of stroke.
AB  - BACKGROUND AND PURPOSE: Epidemiological studies have demonstrated a high
      incidence of infections after severe stroke and their prominent role in morbidity
      and mortality in stroke patients. In a mouse model, it has been shown recently
      that stroke is coupled with severe and long-lasting immunosuppression, which is
      responsible for the development of spontaneous systemic infections. Here, we
      investigated in the same model the effects of preventive antibiotic treatment on
      survival and functional outcome of experimental stroke. METHODS: Mice were
      subjected to experimental stroke by occlusion of the middle cerebral artery
      (MCAO) for 60 minutes. A group of mice received moxifloxacin (6x100 mg/kg body
      weight every 2 hours over 12 hours) either immediately or 12 hours after MCAO.
      Control animals received the vector only. Behavior, neurological deficit, fever,
      survival, and body weight were monitored over 14 days. In a subgroup, infarct
      volume was measured 4 days after MCAO. Microbiological assessment was based on
      cultures of lung tissue, blood, and feces of animals 3 days after stroke. For a
      dose-response study, moxifloxacin was given immediately after MCAO in different
      doses and at different time points. RESULTS: Microbiological analyses of blood
      and lung tissue demonstrated high bacterial burden, mainly Escherichia coli, 3
      days after stroke. Accordingly, we observed clinical and histological signs of
      septicemia and pneumonia. Moxifloxacin prevented the development of infections
      and fever, significantly reduced mortality, and improved neurological outcome.
      CONCLUSIONS: Preventive antibiotic treatment may be an important new
      therapeutical approach to improve outcome in patients with severe stroke.

PMID- 14684768
TI  - Editorial comment--stroke cost-effectiveness research: are acceptability curves
      acceptable?

PMID- 14684769
TI  - Early ischemic signs should not be used as exclusion criteria in thrombolysis
      trials.

PMID- 14684770
TI  - Predicting functional outcome after intra-arterial thrombolysis: aspects of
      ASPECTS.

PMID- 14684771
TI  - Defining the natural history of unruptured aneurysms.

PMID- 14684772
TI  - "Conception origin" versus "fetal origins" hypothesis and stroke.

PMID- 14684773
TI  - Systematic review of methods and results of studies of the genetic epidemiology
      of ischemic stroke.
AB  - BACKGROUND AND PURPOSE: To design appropriate molecular genetic studies, we first
      need to understand the genetic epidemiology of stroke. We therefore performed a
      systematic review of the literature to assess the heritability of stroke
      according to methodological quality of studies and to determine any heterogeneity
      in findings between studies and possible publication bias. METHODS: We searched
      for twin studies and studies of family history of stroke using bibliographic
      databases and by hand-searching reference lists and journals. Odds ratios (ORs)
      for family history as a risk factor for stroke were calculated within studies and
      combined by meta-analysis. Heterogeneity between studies, methodological quality
      of studies, and the influence of the age at which stroke occurred in both
      probands and relatives were assessed. RESULTS: We identified 53 independent
      studies (3 twin, 33 case-control, and 17 cohort). Monozygotic twins were more
      likely to be concordant than dizygotic twins (OR, 1.65; 95% CI, 1.2 to 2.3;
      P=0.003). A positive family history was a risk factor for stroke in both case
      control (OR, 1.76; 95% CI, 1.7 to 1.9; P<0.00001) and cohort (OR, 1.30; 95% CI,
      1.2 to 1.5; P<0.00001) studies. However, there was major heterogeneity between
      studies (cohort P=0.0001; case-control P<0.00001), with much stronger
      associations in small studies and methodologically less rigorous studies.
      Moreover, studies that reported insufficient data to allow meta-analysis tended
      to have found weaker associations. Family history of stroke was more frequent in
      studies that were confined to probands or relatives aged <70 years. However, few
      studies considered the number of affected and unaffected relatives, only 2
      studies considered stroke phenotypes in detail, and only 19 studies (38%)
      adjusted associations for intermediate phenotypes. No twin study, only 5 cohort
      studies (26%), and 20 case-control studies (61%) differentiated between ischemic
      and hemorrhagic stroke in the proband. Family history of stroke was more frequent
      in large- and small-vessel stroke than in cardioembolic stroke. There were very
      few data on the influence of family history on stroke severity and no data on
      stroke recovery. CONCLUSIONS: Twin studies suggest a small genetic contribution
      to stroke, but reliable interpretation of published family history studies is
      undermined by major heterogeneity, insufficient detail, and potential publication
      and reporting bias. More detailed large-scale genetic epidemiology is required.

PMID- 14684774
TI  - Long-term ambulatory monitoring for cerebral emboli using transcranial Doppler
      ultrasound.
AB  - BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) monitoring for asymptomatic
      cerebral emboli is currently limited to short recordings by equipment size,
      restricting its clinical usefulness. We have developed a first ambulatory TCD
      system, evaluated it in at-risk patient groups, and used it to study the pattern
      of embolization in patients with symptomatic carotid stenosis. METHODS: The
      system comprises an 18x11.5x3.2 cm battery-powered Doppler unit (425 g) and a 13
      mm servo-controlled 2 MHz transducer probe. The quadrature raw Doppler signal is
      stored on flash-disk. An autosearch algorithm restores vessel insonation should
      signal quality fall. Initial evaluation was in 20 ambulatory stroke patients.
      Subsequently, 12 recently symptomatic carotid patients had recordings for > or =5
      hours. RESULTS: Recordings were well tolerated and a median of 96% of Doppler
      signal was suitable for analysis. Embolic signals were detected in 11 of the 12
      symptomatic carotid patients. There was marked temporal variability in
      embolization and prolonging the recording increased the yield of embolic signal
      positive patients from 58% at 30 minutes to 92% at 150 minutes. In 3 subjects
      with frequent embolic signals, significant temporal clustering of embolic signals
      was observed. CONCLUSIONS: We have developed the first ambulatory TCD system.
      Good-quality recordings of > or =5 hours can be obtained. In view of the
      demonstrated temporal variability in embolization, this technique is likely to
      improve the predictive value of recording for asymptomatic embolic signals and
      may be particularly useful in patients in whom embolic signals are relatively
      infrequent, such as those with asymptomatic carotid stenosis and atrial
      fibrillation.

PMID- 14684775
TI  - Improved detection of microbubble signals using power M-mode Doppler.
AB  - Background- Power motion-mode transcranial Doppler (TCD) (PMD) is a new,
      multigated technique that may simplify and enhance detection of embolus. We
      developed criteria for emboli detection using PMD. Then, we performed a blinded
      comparison of transcranial PMD with single-gate spectral TCD in TCD bubble study
      patients. METHODS: Patients with right-to-left shunt as detected with standard
      TCD were selected for this study. The international emboli criteria for spectral
      TCD were used. We defined novel PMD criteria for detecting emboli signature on
      PMD as follows: (1) signature at least 3 dB higher than the highest spontaneous
      PMD display of background blood flow; (2) embolic signature reflects motion in
      one direction at a minimum spatial extent of 7.5 mm and temporal extent of 30 ms;
      (3) embolus must traverse a prespecified depth. Each study was blindly assessed
      for microbubble signals (MBS) count on either modality. RESULTS: Thirty-six
      patients were included in the study. Mean age was 44.4 (SD 14.4), 50% were male,
      and median time from stroke onset to TCD bubble test was 12 days. Median MBS
      count in middle cerebral arteries (MCA) was 4 on both modalities. Spectral TCD
      MBS counts were highly correlated (rho=0.97) with PMD MBS counts in MCA and
      similarly in anterior cerebral arteries (ACA) (rho=0.79). When PMD microbubble
      counts in the ACA and MCA were summed, a clear 2-fold difference emerged between
      2 modalities (P<0.001). CONCLUSIONS: When compared with spectral TCD, PMD detects
      more MBS with higher counts by identifying ACA as well as MCA emboli. Pitfalls of
      overcounting emboli with PMD can be avoided by following such criteria.

PMID- 14684776
TI  - Age and National Institutes of Health Stroke Scale Score within 6 hours after
      onset are accurate predictors of outcome after cerebral ischemia: development and
      external validation of prognostic models.
AB  - BACKGROUND AND PURPOSE: To date, no validated, comprehensive, and practicable
      model exists to predict functional recovery within the first hours of cerebral
      ischemic symptoms. The purpose of this study was to externally validate 2
      prognostic models predicting functional outcome and survival at 100 days within
      the first 6 hours after onset of acute cerebral ischemia. METHODS: On admission
      to a participating hospital, patients were registered prospectively and included
      according to defined criteria. Follow-up was performed 100 days after the event.
      With the use of prospectively collected data, 2 prognostic models were developed
      and internally calibrated in 1079 patients and externally validated in 1307
      patients. By means of age and National Institutes of Health Stroke Scale (NIHSS)
      score as independent variables, model I predicts incomplete functional recovery
      (Barthel Index <95) versus complete functional recovery, and model II predicts
      mortality versus survival. RESULTS: In the validation data set, model I correctly
      predicted 62.9% of the patients who were incompletely restituted or had died and
      83.2% of the completely restituted patients, and model II correctly predicted
      57.9% of the patients who had died and 91.5% of the surviving patients. Both
      models performed better than the treating physicians' predictions made within 6
      hours after admission. CONCLUSIONS: The resulting prognostic models are useful to
      correctly stratify treatment groups in clinical trials and should guide inclusion
      criteria in clinical trials, which in turn increases the power to detect
      clinically relevant differences.

PMID- 14684777
TI  - Transcranial Doppler and near-infrared spectroscopy can evaluate the hemodynamic
      effect of carotid artery occlusion.
AB  - BACKGROUND AND PURPOSE: Cerebral hemodynamic and metabolic changes can compensate
      for the decrease in cerebral blood flow occurring in patients with carotid
      occlusive disease. At present, a complete assessment of the cerebral adaptive
      status is only possible with positron-emission tomography. Near-infrared
      spectroscopy (NIRS) is a noninvasive technique that, providing a real time
      assessment of fluctuations in cerebral hemoglobin, has been used to estimate the
      cerebral blood volume and to measure cerebral vasomotor reactivity (VMR).
      Moreover, NIRS technology, by allowing the absolute measurement of absorption and
      scattering coefficients of brain, can determine the oxyhemoglobin and
      deoxyhemoglobin concentrations in situ in the blood stream. METHODS: In order to
      evaluate different aspects of the cerebral hemodynamic status, 27 subjects with
      symptomatic and asymptomatic carotid artery occlusion and 30 healthy subjects
      underwent a simultaneous examination by means of transcranial Doppler (TCD), able
      to reliably detect collateral circulation and VMR, and NIRS at rest condition and
      during CO2 reactivity test. RESULTS: The main finding of this study was the
      demonstration of a difference between asymptomatic and symptomatic patients in
      terms of mean flow velocity increase (52.4% versus 21.0%; P<0.001) estimated by
      TCD and of hemoglobin saturation increase measured by NIRS (6.8% versus 3.8%;
      P=0.015). CONCLUSIONS: The opportunity to perform NIRS and TCD simultaneously
      provides useful information about both hemodynamic and metabolic cerebral
      adaptive status in patients with occlusive disease in a simple, noninvasive, and
      reliable way.

PMID- 14684778
TI  - Multi-Slice CT angiography in diagnosing total versus near occlusions of the
      internal carotid artery: comparison with catheter angiography.
AB  - BACKGROUND AND PURPOSE: To determine the accuracy of multislice computed
      tomographic (CT) angiography in diagnosing total versus near occlusions of the
      internal carotid artery (ICA). METHODS: Fifty-seven ICA total or near occlusions
      identified by catheter angiography were studied with multislice CT angiography 1
      to 3 days after catheter angiography. CT angiography in diagnosing total versus
      near occlusions was analyzed by 2 radiologists independently. The results were
      compared with those of catheter angiography. RESULTS: Catheter angiography
      depicted 31 total occlusions, including 10 without a stump, 19 with a stump <2
      cm, and 2 with a stump >2 cm. Among them, 22 had a downward extent of the
      retrograde ICA flow at or above the carotid siphon, 8 at the carotid canal, and 1
      at the distal cervical ICA. Catheter angiography depicted 26 near occlusions,
      including 21 with a tight stenosis at the proximal third cervical ICA, 1 at the
      middle third, and 4 at the carotid canal or siphon. CT angiography correctly
      depicted all total and near occlusions. In total occlusions, the length of the
      stump and the retrograde flow were all accurately described by CT angiography. In
      near occlusions, the sites of tight stenoses were also correctly identified by CT
      angiography. CONCLUSIONS: Multislice CT angiography had an excellent correlation
      with catheter angiography in diagnosing total versus near occlusion of the ICA.
      It may be considered as a substitute of catheter angiography in confirming the
      ultrasonographic results in diagnosing total versus near occlusions of the ICA.

PMID- 14684779
TI  - Steroids for stroke: another potential therapy discarded prematurely?

PMID- 14684780
TI  - Steroids have no role in stroke therapy.

PMID- 14684781
TI  - Steroids may have a role in stroke therapy.

PMID- 14684782
TI  - Acquired immunodeficiency syndrome and the risk of stroke.
AB  - BACKGROUND AND PURPOSE: Although acquired immunodeficiency syndrome (AIDS) is
      thought to increase the risk of stroke, few data exist to quantify this risk.
      This is the first population-based study to quantify the AIDS-associated risk of
      stroke. METHODS: We identified all incident ischemic stroke (IS) and
      intracerebral hemorrhage (ICH) cases among young adults 15 to 44 years of age in
      central Maryland and Washington, DC, who were discharged from any of the 46
      hospitals in the study area in 1988 and 1991. Using data from the medical
      records, 2 neurologists reviewed each case to confirm the diagnosis. Cases of
      AIDS among these patients with stroke were defined using Centers for Disease
      Control and Prevention criteria (1987). The number of cases of AIDS in the
      central Maryland and Washington population during 1988 and 1991 was determined
      from regional health departments working with the Centers for Disease Control and
      Prevention. Poisson regression was used to estimate the age-, race-, and sex
      adjusted relative risk of stroke associated with AIDS. RESULTS: There were 385 IS
      cases (6 with AIDS) and 171 ICH cases (6 with AIDS). The incidences of IS and ICH
      among persons with AIDS were both 0.2% per year. AIDS conferred an adjusted
      relative risk of 13.7 (95% confidence interval [CI], 6.1 to 30.8) for IS and 25.5
      (95% CI, 11.2 to 58.0) for ICH. After exclusion of 5 cases of stroke in AIDS
      patients in whom other potential causes were identified, AIDS patients continued
      to have an increased risk of stroke with an adjusted relative risk of 9.1 (95%
      CI, 3.4 to 24.6) for IS and 12.7 (95% CI, 4.0 to 40.0) for ICH. CONCLUSIONS: This
      population-based study found that AIDS is strongly associated with both IS and
      ICH.

PMID- 14684783
TI  - Alternative strategies for stroke care: cost-effectiveness and cost-utility
      analyses from a prospective randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: Although stroke units reduce mortality and
      institutionalization, their comparative cost-effectiveness is unknown. METHODS:
      Healthcare, social services, and informal care costs were compared for 447 acute
      stroke patients randomly assigned to stroke unit, stroke team, or domiciliary
      stroke care. Prospective and retrospective methods were used to identify resource
      use over 12 months after stroke onset. Cost-effectiveness and cost-utility
      analyses were undertaken. RESULTS: Mean healthcare and social care costs over 12
      months were 11 450 pounds sterling for stroke unit, 9527 pounds sterling for
      stroke team, and 6840 pounds sterling for domiciliary care. More than half the
      costs were for the initial episode of care. Institutionalization was a large
      proportion of follow-up costs. Inclusion of informal care increased costs
      considerably. When informal care was excluded, the incremental cost-effectiveness
      ratio per percentage point in deaths or institutionalizations avoided in the
      first year was 496 pounds sterling for the stroke unit over domiciliary care;
      incremental cost per quality-adjusted life year quality-adjusted life year gained
      was 64 097 pounds sterling between these 2 groups. The stroke team was dominated
      by domiciliary care. CONCLUSIONS: Cost perspectives, especially those related to
      long-term and informal care, are important when stroke services are evaluated.
      Improved health outcomes in the stroke unit come at a higher cost.

PMID- 14684784
TI  - Editorial comment--spasticity after stroke: what's the catch?

PMID- 14684785
TI  - Spasticity after stroke: its occurrence and association with motor impairments
      and activity limitations.
AB  - BACKGROUND AND PURPOSE: There is no consensus concerning the number of patients
      developing spasticity or the relationship between spasticity and disabilities
      after acute stroke. The aim of the present study was to describe the extent to
      which spasticity occurs and is associated with disabilities (motor impairments
      and activity limitations). METHODS: Ninety-five patients with first-ever stroke
      were examined initially (mean, 5.4 days) and 3 months after stroke with the
      Modified Ashworth Scale for spasticity; self-reported muscle stiffness; tendon
      reflexes; Birgitta Lindmark motor performance; Nine Hole Peg Test for manual
      dexterity; Rivermead Mobility Index; Get-Up and Go test; and Barthel Index.
      RESULTS: Of the 95 patients studied, 64 were hemiparetic, 18 were spastic, 6
      reported muscle stiffness, and 18 had increased tendon reflexes 3 months after
      stroke. Patients who were nonspastic (n=77) had statistically significantly
      better motor and activity scores than spastic patients (n=18). However, the
      correlations between muscle tone and disability scores were low, and severe
      disabilities were seen in almost the same number of nonspastic as spastic
      patients. CONCLUSIONS: Although spasticity seems to contribute to disabilities
      after stroke, spasticity was present in only 19% of the patients investigated 3
      months after stroke. Severe disabilities were seen in almost the same number of
      nonspastic as spastic patients. These findings indicate that the focus on
      spasticity in stroke rehabilitation is out of step with its clinical importance.
      Careful and continual evaluation to establish the cause of the patient's
      disabilities is essential before a decision is made on the most proper
      rehabilitation approach.

PMID- 14684787
TI  - Breakthrough of the year. Illuminating the dark universe.

PMID- 14684786
TI  - Breakthrough of the year.

PMID- 14684788
TI  - Breakthrough of the year. Areas to watch in 2004.

PMID- 14684789
TI  - Breakthrough of the year. Scorecard 2002.

PMID- 14684790
TI  - Breakthrough of the year. Breakdown of the year: Space Shuttle Columbia.

PMID- 14684791
TI  - Breakthrough of the year. SARS: a pandemic prevented.

PMID- 14684793
TI  - Astronomy. Spitzer Space Telescope (ne IRTF) sparkles in debut.

PMID- 14684792
TI  - Conflict of interest. Zerhouni pledges review of NIH consulting in wake of
      allegations.

PMID- 14684794
TI  - Ecology. Too much crunching on rainforest nuts?

PMID- 14684795
TI  - Cell biology. In sex reversal, protein deterred by nuclear barrier.

PMID- 14684796
TI  - Genome sequencing. Cow ambles to the sequencing house.

PMID- 14684797
TI  - Astrophysics. Gamma ray satellite sees out first year with a bang.

PMID- 14684798
TI  - Ecology. Bye, bye Biosphere 2.

PMID- 14684799
TI  - Scientific community. The trials of Thomas Butler.

PMID- 14684800
TI  - Scientific community. African study raises ethical issues.

PMID- 14684801
TI  - Scientific community. Butler's samples spelled trouble for U.S. agencies.

PMID- 14684802
TI  - Scientific community. The final score: 47 to 22.

PMID- 14684803
TI  - Revisiting Amazonia circa 1492.

PMID- 14684804
TI  - A gross indignity to humans.

PMID- 14684805
TI  - An unseemly display of mortality?

PMID- 14684806
TI  - Science and government. Disclosure in regulatory science.

PMID- 14684807
TI  - Evolution. Climb every mountain?

PMID- 14684808
TI  - Geology. How to concentrate copper.

PMID- 14684809
TI  - Computer science. Randomness in quantum computation.

PMID- 14684810
TI  - Developmental biology. Tubulogenesis CLICs into place.

PMID- 14684811
TI  - Neuroscience. ORs rule the roost in the olfactory system.

PMID- 14684812
TI  - Long-term ecosystem response to the Exxon Valdez oil spill.
AB  - The ecosystem response to the 1989 spill of oil from the Exxon Valdez into Prince
      William Sound, Alaska, shows that current practices for assessing ecological
      risks of oil in the oceans and, by extension, other toxic sources should be
      changed. Previously, it was assumed that impacts to populations derive almost
      exclusively from acute mortality. However, in the Alaskan coastal ecosystem,
      unexpected persistence of toxic subsurface oil and chronic exposures, even at
      sublethal levels, have continued to affect wildlife. Delayed population
      reductions and cascades of indirect effects postponed recovery. Development of
      ecosystem-based toxicology is required to understand and ultimately predict
      chronic, delayed, and indirect long-term risks and impacts.

PMID- 14684813
TI  - Generation of viable cholesterol-free mice.

PMID- 14684815
TI  - Pseudo-random unitary operators for quantum information processing.
AB  - In close analogy to the fundamental role of random numbers in classical
      information theory, random operators are a basic component of quantum information
      theory. Unfortunately, the implementation of random unitary operators on a
      quantum processor is exponentially hard. Here we introduce a method for
      generating pseudo-random unitary operators that can reproduce those statistical
      properties of random unitary operators most relevant to quantum information
      tasks. This method requires exponentially fewer resources, and hence enables the
      practical application of random unitary operators in quantum communication and
      information processing protocols. Using a nuclear magnetic resonance quantum
      processor, we were able to realize pseudorandom unitary operators that reproduce
      the expected random distribution of matrix elements.

PMID- 14684814
TI  - Biomolecular interactions at phospholipid-decorated surfaces of liquid crystals.
AB  - The spontaneous assembly of phospholipids at planar interfaces between
      thermotropic liquid crystals and aqueous phases gives rise to patterned
      orientations of the liquid crystals that reflect the spatial and temporal
      organization of the phospholipids. Strong and weak specific-binding events
      involving proteins at these interfaces drive the reorganization of the
      phospholipids and trigger orientational transitions in the liquid crystals.
      Because these interfaces are fluid, processes involving the lateral organization
      of proteins (such as the formation of protein- and phospholipid-rich domains) are
      also readily imaged by the orientational response of the liquid crystal, as are
      stereospecific enzymatic events. These results provide principles for label-free
      monitoring of aqueous streams for molecular and biomolecular species without the
      need for complex instrumentation.

PMID- 14684816
TI  - Observation of two distinct superconducting phases in CeCu2Si2.
AB  - We report the presence of two disconnected superconducting domes in the pressure
      temperature phase diagram of partially germanium-substituted CeCu2Si2. The lower
      density superconducting dome lies on the threshold of antiferromagnetic order,
      indicating magnetically mediated pairing, whereas the higher density
      superconducting regime straddles a weakly first-order volume collapse, suggesting
      a pairing interaction based on spatially extended density fluctuations. Two
      distinct pairing mechanisms thus appear to operate in the single, wide,
      superconducting range of stoichiometric CeCu2Si2, both of which might apply more
      generally to other classes of correlated electron systems.

PMID- 14684817
TI  - Adaptation limits diversification of experimental bacterial populations.
AB  - Adaptation to a specific niche theoretically constrains a population's ability to
      subsequently diversify into other niches. We tested this theory using the
      bacterium Pseudomonas fluorescens, which diversifies into niche specialists when
      propagated in laboratory microcosms. Numerically dominant genotypes were allowed
      to diversify in isolation. As predicted, populations increased in fitness through
      time but showed a greatly decreased ability to diversify. Subsequent experiments
      demonstrated that niche generalists and reductions in intrinsic evolvability were
      not responsible for our data. These results show that niche specialization may
      come with a cost of reduced potential to diversify.

PMID- 14684818
TI  - Melt inclusions in veins: linking magmas and porphyry Cu deposits.
AB  - At a porphyry copper-gold deposit in Bajo de la Alumbrera, Argentina, silicate
      melt inclusions coexist with hypersaline liquid- and vapor-rich inclusions in the
      earliest magmatic-hydrothermal quartz veins. Copper concentrations of the
      hypersaline liquid and vapor inclusions reached maxima of 10.0 weight % (wt %)
      and 4.5 wt %, respectively. These unusually copper-rich inclusions are considered
      to be the most primitive ore fluid found thus far. Their preservation with
      coexisting melt allows for the direct quantification of important oreforming
      processes, including determination of bulk partition coefficients of metals from
      magma into ore-forming magmatic volatile phases.

PMID- 14684819
TI  - Demographic threats to the sustainability of Brazil nut exploitation.
AB  - A comparative analysis of 23 populations of the Brazil nut tree (Bertholletia
      excelsa) across the Brazilian, Peruvian, and Bolivian Amazon shows that the
      history and intensity of Brazil nut exploitation are major determinants of
      population size structure. Populations subjected to persistent levels of harvest
      lack juvenile trees less than 60 centimeters in diameter at breast height; only
      populations with a history of either light or recent exploitation contain large
      numbers of juvenile trees. A harvesting model confirms that intensive
      exploitation levels over the past century are such that juvenile recruitment is
      insufficient to maintain populations over the long term. Without management,
      intensively harvested populations will succumb to a process of senescence and
      demographic collapse, threatening this cornerstone of the Amazonian extractive
      economy.

PMID- 14684820
TI  - Maize genome sequencing by methylation filtration.
AB  - Gene enrichment strategies offer an alternative to sequencing large and
      repetitive genomes such as that of maize. We report the generation and analysis
      of nearly 100,000 undermethylated (or methylation filtration) maize sequences.
      Comparison with the rice genome reveals that methylation filtration results in a
      more comprehensive representation of maize genes than those that result from
      expressed sequence tags or transposon insertion sites sequences. About 7% of the
      repetitive DNA is unmethylated and thus selected in our libraries, but
      potentially active transposons and unmethylated organelle genomes can be
      identified. Reverse transcription polymerase chain reaction can be used to finish
      the maize transcriptome.

PMID- 14684821
TI  - Enrichment of gene-coding sequences in maize by genome filtration.
AB  - Approximately 80% of the maize genome comprises highly repetitive sequences
      interspersed with single-copy, gene-rich sequences, and standard genome
      sequencing strategies are not readily adaptable to this type of genome.
      Methodologies that enrich for genic sequences might more rapidly generate useful
      results from complex genomes. Equivalent numbers of clones from maize selected by
      techniques called methylation filtering and High C0t selection were sequenced to
      generate approximately 200,000 reads (approximately 132 megabases), which were
      assembled into contigs. Combination of the two techniques resulted in a sixfold
      reduction in the effective genome size and a fourfold increase in the gene
      identification rate in comparison to a nonenriched library.

PMID- 14684822
TI  - Dual activation of the Drosophila toll pathway by two pattern recognition
      receptors.
AB  - The Toll-dependent defense against Gram-positive bacterial infections in
      Drosophila is mediated through the peptidoglycan recognition protein SA (PGRP
      SA). A mutation termed osiris disrupts the Gram-negative binding protein 1
      (GNBP1) gene and leads to compromised survival of mutant flies after Gram
      positive infections, but not after fungal or Gram-negative bacterial challenge.
      Our results demonstrate that GNBP1 and PGRP-SA can jointly activate the Toll
      pathway. The potential for a combination of distinct proteins to mediate
      detection of infectious nonself in the fly will refine the concept of pattern
      recognition in insects.

PMID- 14684823
TI  - A C. elegans CLIC-like protein required for intracellular tube formation and
      maintenance.
AB  - The Caenorhabditis elegans excretory canal is composed of a single elongated and
      branched cell that is tunneled by an inner lumen of apical character. Loss of the
      exc-4 gene causes a cystic enlargement of this intracellular tube. exc-4 encodes
      a member of the chloride intracellular channel (CLIC) family of proteins. EXC-4
      protein localizes to various tubular membranes in distinct cell types, including
      the lumenal membrane of the excretory tubes. A conserved 55-amino acid domain
      enables EXC-4 translocation from the cytosol to the lumenal membrane. The tubular
      architecture of this membrane requires EXC-4 for both its formation and
      maintenance.

PMID- 14684824
TI  - Transcription-coupled events associating with immunoglobulin switch region
      chromatin.
AB  - Class switch recombination (CSR) at the antibody immunoglobulin locus is
      regulated by germline transcription (GLT)-coupled modifications in the
      accessibility of the switch region, where CSR takes place. Here we show that
      histone acetylation of switch regions is linked to CSR but that histone
      acetylation cannot alone promote CSR or GLT. Activation-induced cytidine
      deaminase (AID) specifically associates with the CSR target chromatin in a GLT
      coupled manner, which may occur potentially by means of physical interaction
      between AID and the transcription machinery. These data indicate an important
      role of GLT in the regulation of chromatin accessibility, strongly suggesting
      that the target of AID is chromatin DNA. Our results give insights on the role of
      AID and the regulatory mechanism of CSR.

PMID- 14684825
TI  - Genome-wide survey of human alternative pre-mRNA splicing with exon junction
      microarrays.
AB  - Alternative pre-messenger RNA (pre-mRNA) splicing plays important roles in
      development, physiology, and disease, and more than half of human genes are
      alternatively spliced. To understand the biological roles and regulation of
      alternative splicing across different tissues and stages of development,
      systematic methods are needed. Here, we demonstrate the use of microarrays to
      monitor splicing at every exon-exon junction in more than 10,000 multi-exon human
      genes in 52 tissues and cell lines. These genome-wide data provide experimental
      evidence and tissue distributions for thousands of known and novel alternative
      splicing events. Adding to previous studies, the results indicate that at least
      74% of human multi-exon genes are alternatively spliced.

PMID- 14684826
TI  - Transformation of olfactory representations in the Drosophila antennal lobe.
AB  - Molecular genetics has revealed a precise stereotypy in the projection of primary
      olfactory sensory neurons onto secondary neurons. A major challenge is to
      understand how this mapping translates into odor responses in these second-order
      neurons. We investigated this question in Drosophila using whole-cell recordings
      in vivo. We observe that monomolecular odors generally elicit responses in large
      ensembles of antennal lobe neurons. Comparison of odor-evoked activity from
      afferents and postsynaptic neurons in the same glomerulus revealed that second
      order neurons display broader tuning and more complex responses than their
      primary afferents. This indicates a major transformation of odor representations,
      implicating lateral interactions within the antennal lobe.

PMID- 14684827
TI  - Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins.
AB  - It is now established that CD1 molecules present lipid antigens to T cells,
      although it is not clear how the exchange of lipids between membrane compartments
      and the CD1 binding groove is assisted. We report that mice deficient in
      prosaposin, the precursor to a family of endosomal lipid transfer proteins (LTP),
      exhibit specific defects in CD1d-mediated antigen presentation and lack Valpha14
      NKT cells. In vitro, saposins extracted monomeric lipids from membranes and from
      CD1, thereby promoting the loading as well as the editing of lipids on CD1.
      Transient complexes between CD1, lipid, and LTP suggested a "tug-of-war" model in
      which lipid exchange between CD1 and LTP is on the basis of their respective
      affinities for lipids. LTPs constitute a previously unknown link between lipid
      metabolism and immunity and are likely to exert a profound influence on the
      repertoire of self, tumor, and microbial lipid antigens.

PMID- 14684828
TI  - Kinesin walks hand-over-hand.
AB  - Kinesin is a processive motor that takes 8.3-nm center-of-mass steps along
      microtubules for each adenosine triphosphate hydrolyzed. Whether kinesin moves by
      a "hand-over-hand" or an "inchworm" model has been controversial. We have labeled
      a single head of the kinesin dimer with a Cy3 fluorophore and localized the
      position of the dye to within 2 nm before and after a step. We observed that
      single kinesin heads take steps of 17.3 +/- 3.3 nm. A kinetic analysis of the
      dwell times between steps shows that the 17-nm steps alternate with 0-nm steps.
      These results strongly support a hand-over-hand mechanism, and not an inchworm
      mechanism. In addition, our results suggest that kinesin is bound by both heads
      to the microtubule while it waits for adenosine triphosphate in between steps.

PMID- 14684829
TI  - Neurotoxic effects of polymorphonuclear granulocytes on hippocampal primary
      cultures.
AB  - Many neurological insults and neurodegenerative disorders are accompanied by an
      acute inflammatory reaction that can contribute to neuronal damage. This
      inflammation involves infiltration of bloodborne polymorphonuclear leukocytes
      (PMNs) into the injured brain area. The role of inflammation in brain injury,
      however, is controversial, because recent studies suggest that inflammation may
      actually be beneficial in the recovery from brain damage. Therefore, we
      investigated the effects of pathophysiologically relevant concentrations of PMNs
      in vitro on mixed hippocampal primary cultures. Rat PMNs and peripheral blood
      lymphocytes were isolated by density centrifugation and cocultured with
      hippocampal cells for 24-72 h plus or minus an excitotoxic insult (50 microM
      kainic acid) or 6-h oxygen glucose deprivation. Cell death was analyzed by
      immunocytochemistry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide assay, and neuron-specific [2,2'-azino-bis(ethylbenzothiazoline-6
      sulfonic acid)] assay. After 3 days of coculture in the absence of insult, PMNs
      caused massive neuron loss and dramatic morphological changes in glial cells
      (astrocyte detachment, aggregation). Furthermore PMNs exacerbated kainic acid-
      and oxygen glucose deprivation-induced neuron death by 20-30%. The cytotoxic
      effect of PMNs required heterocellular contact and were ameliorated by protease
      inhibitors. Lymphocytes, on the other hand, were not neurotoxic, but, instead,
      increased astrocyte proliferation. These findings suggest that PMN might
      represent a harmful part of inflammation after brain injury that can contribute
      to secondary damage.

PMID- 14684830
TI  - Guanylyl cyclase is an ATP sensor coupling nitric oxide signaling to cell
      metabolism.
AB  - Defending cellular integrity against disturbances in intracellular concentrations
      of ATP ([ATP](i)) is predicated on coordinating the selection of substrates and
      their flux through metabolic pathways (metabolic signaling), ATP transfer from
      sites of production to utilization (energetic signaling), and the regulation of
      processes consuming energy (cell signaling). Whereas NO and its receptor, soluble
      guanylyl cyclase (sGC), are emerging as key mediators coordinating ATP supply and
      demand, mechanisms coupling this pathway with metabolic and energetic signaling
      remain undefined. Here, we demonstrate that sGC is a nucleotide sensor whose
      responsiveness to NO is regulated by [ATP](i). Indeed, ATP inhibits purified sGC
      with a K(i) predicting >60% inhibition of NO signaling in cells maintaining
      physiological [nucleotide](i). ATP inhibits sGC by interacting with a regulatory
      site that prefers ATP > GTP. Moreover, alterations in [ATP](i), by
      permeabilization and nucleotide clamping or inhibition of mitochondrial ATP
      synthase, regulate NO signaling by sGC. Thus, [ATP](i) serves as a "gain control"
      for NO signaling by sGC. At homeostatic [ATP](i), NO activation of sGC is
      repressed, whereas insults that reduce [ATP](i,) derepress sGC and amplify
      responses to NO. Hence, sGC forms a key synapse integrating metabolic, energetic,
      and cell signaling, wherein ATP is the transmitter, allosteric inhibition the
      coupling mechanism, and regulated accumulation of cGMP the response.

PMID- 14684832
TI  - Pharmacogenetic rescue in time and space of the rutabaga memory impairment by
      using Gene-Switch.
AB  - The GAL4-based Gene-Switch system has been engineered to regulate transgene
      expression in Drosophila in both time and space. We constructed a Gene-Switch
      transgene in which Gene-Switch expression is restricted spatially by a defined
      mushroom body enhancer. This system allows Gene-Switch to be active only in the
      mushroom bodies and only on administration of the pharmacological Gene-Switch
      ligand RU486. This line was used to drive the expression of a rutabaga cDNA in
      otherwise rutabaga mutant flies. Induction of the rutabaga cDNA in the mushroom
      bodies only during adulthood, or during adulthood along with the larval and pupal
      developmental stages, corrects the olfactory memory impairment found in rutabaga
      mutants. Induction of the cDNA only during the larval and pupal stages was
      inconsequential to performance in olfactory memory tasks. These data indicate
      that normal rutabaga function must be expressed in adulthood for normal memory
      and conclusively delimit the time and space expression requirements for
      correcting the rutabaga memory impairment. Such combined pharmacogenetic
      regulation of transgene expression now allows this time and space dissection to
      be made for other behavioral mutants.

PMID- 14684831
TI  - Crystal structure of a central stalk subunit C and reversible
      association/dissociation of vacuole-type ATPase.
AB  - The vacuole-type ATPases (V-ATPases) exist in various intracellular compartments
      of eukaryotic cells to regulate physiological processes by controlling the acidic
      environment. The crystal structure of the subunit C of Thermus thermophilus V
      ATPase, homologous to eukaryotic subunit d of V-ATPases, has been determined at
      1.95-A resolution and located into the holoenzyme complex structure obtained by
      single particle analysis as suggested by the results of subunit cross-linking
      experiments. The result shows that V-ATPase is substantially longer than the
      related F-type ATPase, due to the insertion of subunit C between the V(1)
      (soluble) and the V(o) (membrane bound) domains. Subunit C, attached to the V(o)
      domain, seems to have a socket like function in attaching the central-stalk
      subunits of the V(1) domain. This architecture seems essential for the reversible
      association/dissociation of the V(1) and the V(o) domains, unique for V-ATPase
      activity regulation.

PMID- 14684833
TI  - A functional genomic screen for cardiogenic genes using RNA interference in
      developing Drosophila embryos.
AB  - Identifying genetic components is an essential step toward understanding complex
      developmental processes. The primitive heart of the fruit fly, the dorsal vessel,
      which is a hemolymph-pumping organ, has provided a unique model system to
      identify cardiogenic genes and to further our understanding of the molecular
      mechanisms of cardiogenesis. Using RNA interference in developing Drosophila
      embryos, we performed a genomewide search for cardiogenic genes. Through analyses
      of the >5800 genes that cover approximately 40% of all predicted Drosophila
      genes, we identified a variety of genes encoding transcription factors and cell
      signaling proteins required for different steps during heart development.
      Analysis of mutant heart phenotypes and identified genes suggests that the
      Drosophila heart tube is segmentally patterned, like axial patterning, but
      assembled with regional modules. One of the identified genes, simjang, was
      further characterized. In the simjang mutant embryo, we found that within each
      segment a subset of cardial cells is missing. Interestingly, the simjang gene
      encodes a protein that is a component of the chromatin remodeling complex
      recruited by methyl-CpG-DNA binding proteins, suggesting that epigenetic
      information is crucial for specifying cardiac precursors. Together, these studies
      not only identify key regulators but also reveal mechanisms underlying heart
      development.

PMID- 14684834
TI  - Local complexity of amino acid interactions in a protein core.
AB  - Atomic resolution structures of proteins indicate that the core is typically well
      packed, suggesting a densely connected network of interactions between amino acid
      residues. The combinatorial complexity of energetic interactions in such a
      network could be enormous, a problem that limits our ability to relate structure
      and function. Here, we report a case study of the complexity of amino acid
      interactions in a localized region within the core of the GFP, a particularly
      stable and tightly packed molecule. Mutations at three sites within the
      chromophore-binding pocket display an overlapping pattern of conformational
      change and are thermodynamically coupled, seemingly consistent with the dense
      network model. However, crystallographic and energetic analyses of coupling
      between mutations paint a different picture; pairs of mutations couple through
      independent "hotspots" in the region of structural overlap. The data indicate
      that, even in highly stable proteins, the core contains sufficient plasticity in
      packing to uncouple high-order energetic interactions of residues, a property
      that is likely general in proteins.

PMID- 14684835
TI  - Random walks in the history of life.
AB  - The simplest null hypothesis for evolutionary time series is that the observed
      data follow a random walk. We examined whether aspects of Sepkoski's compilation
      of marine generic diversity depart from a random walk by using statistical tests
      from econometrics. Throughout most of the Phanerozoic, the random-walk null
      hypothesis is not rejected for marine diversity, accumulated origination or
      accumulated extinction, suggesting that either these variables were correlated
      with environmental variables that follow a random walk or so many mechanisms were
      affecting these variables, in different ways, that the resultant trends appear
      random. The only deviation from this pattern involves rejection of the null
      hypothesis for roughly the last 75 million years for the diversity and
      accumulated origination time series.

PMID- 14684836
TI  - DNA-methyltransferase 1 mRNA is selectively overexpressed in telencephalic
      GABAergic interneurons of schizophrenia brains.
AB  - A down-regulation of reelin and glutamic acid decarboxylase (GAD) 67 mRNAs was
      detected in gamma-aminobutyric acid (GABA)ergic cortical interneurons of
      schizophrenia (SZ) postmortem brains (10), suggesting that the availability of
      GABA and reelin may be decreased in SZ cortex. In situ hybridization of the mRNA
      encoding for DNA-methyltransferase 1, which catalyzes the methylation of promoter
      CpG islands, shows that the expression of this mRNA is increased in cortical
      GABAergic interneurons but not in pyramidal neurons of SZ brains. Counts of
      reelin mRNA-positive neurons in Brodmann's area 10 of either nonpsychiatric
      subjects or SZ patients show that the expression of reelin mRNA is decreased in
      layer-I, -II, and -IV GABAergic interneurons of SZ patients. These findings are
      consistent with the hypothesis that the increase of DNA-methyltransferase 1
      expression in telencephalic GABAergic interneurons of SZ patients causes a
      promoter hypermethylation of reelin and GAD(67) and perhaps of other genes
      expressed in these interneurons. It is difficult to decide whether this
      dysfunction of GABAergic neurons detected in SZ is responsible for this disease
      or is a consequence of this disorder. Although at present we cannot differentiate
      between these two alternatives, it is important to consider that so far a
      molecular pathology of cortical GABAergic neurons appears to be the most
      consistent finding associated with SZ morbidity.

PMID- 14684837
TI  - Binding of sulfonylurea by AtMRP5, an Arabidopsis multidrug resistance-related
      protein that functions in salt tolerance.
AB  - Recently, a new member of the ABC transporter superfamily of Arabidopsis, AtMRP5,
      was identified and characterized. In the present work, we found that AtMRP5 can
      bind specifically to sulfonurea when it is expressed in HEK293 cells. We also
      present evidence for a new role of AtMRP5 in the salt stress response of
      Arabidopsis. We used reverse genetics to identify an Arabidopsis mutant (atmrp5
      2) in which the AtMRP5 gene was disrupted by transferred DNA insertion. In root
      bending assays using Murashige and Skoog medium supplemented with 100 mm NaCl,
      root growth of atmrp5-2 was substantially inhibited in contrast to the almost
      normal growth of wild-type seedlings. This hypersensitive response of the atmrp5
      2 mutant was not observed during mannitol treatment. The root growth of the wild
      type plant grown in Murashige and Skoog medium supplemented with the MRP
      inhibitor glibenclamide and NaCl was inhibited to a very similar extent as the
      root growth of atmrp5-2 grown in NaCl alone. The Na(+)-dependent reduction of
      root growth of the wild-type plant in the presence of glibenclamide was partially
      restored by diazoxide, a known K+ channel opener that reverses the inhibitory
      effects of sulfonylureas in animal cells. Moreover, the atmrp5-2 mutant was
      defective in 86Rb+ uptake. When seedlings were treated with 100 mm NaCl, atmrp5-2
      seedlings accumulated less K+ and more Na+ than those of the wild type. These
      observations suggest that AtMRP5 is a putative sulfonylurea receptor that is
      involved in K+ homeostasis and, thus, also participates in the NaCl stress
      response.

PMID- 14684838
TI  - Biocontrol of Bacillus subtilis against infection of Arabidopsis roots by
      Pseudomonas syringae is facilitated by biofilm formation and surfactin
      production.
AB  - Relatively little is known about the exact mechanisms used by Bacillus subtilis
      in its behavior as a biocontrol agent on plants. Here, we report the development
      of a sensitive plant infection model demonstrating that the bacterial pathogen
      Pseudomonas syringae pv tomato DC3000 is capable of infecting Arabidopsis roots
      both in vitro and in soil. Using this infection model, we demonstrated the
      biocontrol ability of a wild-type B. subtilis strain 6051 against P. syringae.
      Arabidopsis root surfaces treated with B. subtilis were analyzed with confocal
      scanning laser microscopy to reveal a three-dimensional B. subtilis biofilm. It
      is known that formation of biofilms by B. subtilis is a complex process that
      includes secretion of surfactin, a lipopeptide antimicrobial agent. To determine
      the role of surfactin in biocontrol by B. subtilis, we tested a mutant strain,
      M1, with a deletion in a surfactin synthase gene and, thus, deficient in
      surfactin production. B. subtilis M1 was ineffective as a biocontrol agent
      against P. syringae infectivity in Arabidopsis and also failed to form robust
      biofilms on either roots or inert surfaces. The antibacterial activity of
      surfactin against P. syringae was determined in both broth and agar cultures and
      also by live-dead staining methods. Although the minimum inhibitory
      concentrations determined were relatively high (25 microg mL(-1)), the levels of
      the lipopeptide in roots colonized by B. subtilis are likely to be sufficient to
      kill P. syringae. Our results collectively indicate that upon root colonization,
      B. subtilis 6051 forms a stable, extensive biofilm and secretes surfactin, which
      act together to protect plants against attack by pathogenic bacteria.

PMID- 14684839
TI  - Regulation of K+ transport in tomato roots by the TSS1 locus. Implications in
      salt tolerance.
AB  - The tss1 tomato (Lycopersicon esculentum) mutant exhibited reduced growth in low
      K+ and hypersensitivity to Na+ and Li+. Increased Ca2+ in the culture medium
      suppressed the Na+ hypersensitivity and the growth defect on low K+ medium of
      tss1 seedlings. Interestingly, removing NH4+ from the growth medium suppressed
      all growth defects of tss1, suggesting a defective NH4(+)-insensitive component
      of K+ transport. We performed electrophysiological studies to understand the
      contribution of the NH4(+)-sensitive and -insensitive components of K+ transport
      in wild-type and tss1 roots. Although at 1 mm Ca2+ we found no differences in
      affinity for K+ uptake between wild type and tss1 in the absence of NH4+, the
      maximum depolarization value was about one-half in tss1, suggesting that a set of
      K+ transporters is inactive in the mutant. However, these transporters became
      active by raising the external Ca2+ concentration. In the presence of NH4+, a
      reduced affinity for K+ was observed in both types of seedlings, but tss1 at 1 mm
      Ca2+ exhibited a 2-fold higher Km than wild type did. This defect was again
      corrected by raising the external concentration of Ca2+. Therefore, membrane
      potential measurements in root cells indicated that tss1 is affected in both
      NH4(+)-sensitive and -insensitive components of K+ transport at low Ca2+
      concentrations and that this defective transport is rescued by increasing the
      concentration of Ca2+. Our results suggest that the TSS1 gene product is part of
      a crucial pathway mediating the beneficial effects of Ca2+ involved in K+
      nutrition and salt tolerance.

PMID- 14684841
TI  - Characterization of mutants in Arabidopsis showing increased sugar-specific gene
      expression, growth, and developmental responses.
AB  - Sugars such as sucrose serve dual functions as transported carbohydrates in
      vascular plants and as signal molecules that regulate gene expression and plant
      development. Sugar-mediated signals indicate carbohydrate availability and
      regulate metabolism by co-coordinating sugar production and mobilization with
      sugar usage and storage. Analysis of mutants with altered responses to sucrose
      and glucose has shown that signaling pathways mediated by sugars and abscisic
      acid interact to regulate seedling development and gene expression. Using a novel
      screen for sugar-response mutants based on the activity of a luciferase reporter
      gene under the control of the sugar-inducible promoter of the ApL3 gene, we have
      isolated high sugar-response (hsr) mutants that exhibit elevated luciferase
      activity and ApL3 expression in response to low sugar concentrations. Our
      characterization of these hsr mutants suggests that they affect the regulation of
      sugar-induced and sugar-repressed processes controlling gene expression, growth,
      and development in Arabidopsis. In contrast to some other sugar-response mutants,
      they do not exhibit altered responses to ethylene or abscisic acid, suggesting
      that the hsr mutants may have a specifically increased sensitivity to sugars.
      Further characterization of the hsr mutants will lead to greater understanding of
      regulatory pathways involved in metabolite signaling.

PMID- 14684840
TI  - Salicylic acid is an uncoupler and inhibitor of mitochondrial electron transport.
AB  - The effect of salicylic acid (SA) on respiration and mitochondrial function was
      examined in tobacco (Nicotiana tabacum) suspension cell cultures in the range of
      0.01 to 5 mm. Cells rapidly accumulated SA up to 10-fold of the externally
      applied concentrations. At the lower concentrations, SA accumulation was
      transitory. When applied at 0.1 mm or less, SA stimulated respiration of whole
      cells and isolated mitochondria in the absence of added ADP, indicating
      uncoupling of respiration. However, at higher concentrations, respiration was
      severely inhibited. Measurements of ubiquinone redox poise in isolated
      mitochondria suggested that SA blocked electron flow from the substrate
      dehydrogenases to the ubiquinone pool. This inhibition could be at least
      partially reversed by re-isolating the mitochondria. Two active analogs of SA,
      benzoic acid and acetyl-SA, had the same effect as SA on isolated tobacco
      mitochondria, whereas the inactive p-hydroxybenzoic acid was without effect at
      the same concentration. SA induced an increase in Aox protein levels in cell
      suspensions, and this was correlated with an increase in Aox1 transcript
      abundance. However, when applied at 0.1 mM, this induction was transient and
      disappeared as SA levels in the cells declined. SA at 0.1 mM also increased the
      expression of other SA-responsive genes, and this induction was dependent on
      active mitochondria. The results indicate that SA is both an uncoupler and an
      inhibitor of mitochondrial electron transport and suggest that this underlies the
      induction of some genes by SA. The possible implications of this for the
      interpretation of SA action in plants are discussed.

PMID- 14684842
TI  - Engineering plant shikimate pathway for production of tocotrienol and improving
      herbicide resistance.
AB  - Tocochromanols (tocopherols and tocotrienols), collectively known as vitamin E,
      are essential antioxidant components of both human and animal diets. Because of
      their potential health benefits, there is a considerable interest in plants with
      increased or customized vitamin E content. Here, we have explored a new strategy
      to reach this goal. In plants, phenylalanine is the precursor of a myriad of
      secondary compounds termed phenylpropanoids. In contrast, much less carbon is
      incorporated into tyrosine that provides p-hydroxyphenylpyruvate and
      homogentisate, the aromatic precursors of vitamin E. Therefore, we intended to
      increase the flux of these two compounds by deriving their synthesis directly at
      the level of prephenate. This was achieved by the expression of the yeast
      (Saccharomyces cerevisiae) prephenate dehydrogenase gene in tobacco (Nicotiana
      tabacum) plants that already overexpress the Arabidopsis p-hydroxyphenylpyruvate
      dioxygenase coding sequence. A massive accumulation of tocotrienols was observed
      in leaves. These molecules, which were undetectable in wild-type leaves, became
      the major forms of vitamin E in the leaves of the transgenic lines. An increased
      resistance of the transgenic plants toward the herbicidal p-hydroxyphenylpyruvate
      dioxygenase inhibitor diketonitril was also observed. This work demonstrates that
      the synthesis of p-hydroxyphenylpyruvate is a limiting step for the accumulation
      of vitamin E in plants.

PMID- 14684843
TI  - A post genomic characterization of Arabidopsis ferredoxins.
AB  - In higher plant plastids, ferredoxin (Fd) is the unique soluble electron carrier
      protein located in the stroma. Consequently, a wide variety of essential
      metabolic and signaling processes depend upon reduction by Fd. The currently
      available plant genomes of Arabidopsis and rice (Oryza sativa) contain several
      genes encoding putative Fds, although little is known about the proteins
      themselves. To establish whether this variety represents redundancy or
      specialized function, we have recombinantly expressed and purified the four
      conventional [2Fe-2S] Fd proteins encoded in the Arabidopsis genome and analyzed
      their physical and functional properties. Two proteins are leaf type Fds, having
      relatively low redox potentials and supporting a higher photosynthetic activity.
      One protein is a root type Fd, being more efficiently reduced under
      nonphotosynthetic conditions and supporting a higher activity of sulfite
      reduction. A further Fd has a remarkably positive redox potential and so,
      although redox active, is limited in redox partners to which it can donate
      electrons. Immunological analysis indicates that all four proteins are expressed
      in mature leaves. This holistic view demonstrates how varied and essential
      soluble electron transfer functions in higher plants are fulfilled through a
      diversity of Fd proteins.

PMID- 14684844
TI  - Regulation of inhibitory protein-kappaB and monocyte chemoattractant protein-1 by
      angiotensin II type 2 receptor-activated Src homology protein tyrosine
      phosphatase-1 in fetal vascular smooth muscle cells.
AB  - In the present study we examined the effects of angiotensin II (Ang II) type 2
      (AT(2)) receptor stimulation on AT(1) receptor-mediated monocyte chemoattractant
      protein-1 (MCP-1) expression and the possible mechanisms of AT(2) receptor
      mediated signaling in cultured rat fetal vascular smooth muscle cells, which
      express both AT(1) and AT(2) receptors. Ang II stimulation induced MCP-1 mRNA
      expression as well as an increase in nuclear factor-kappaB (NF-kappaB) binding to
      the corresponding cis DNA element of the MCP-1 promoter region and a decrease in
      the cytosolic inhibitory protein-kappaB (IkappaB) protein level via AT(1)
      receptor stimulation, whereas stimulation of the AT(2) receptor decreased Ang II
      induced MCP-1 expression, NF-kappaB DNA binding, and IkappaB degradation,
      suggesting that activation of the AT(2) receptor attenuated AT(1) receptor
      mediated MCP-1 expression via a decrease in NF-kappaB DNA binding and an increase
      in IkappaB stability. Moreover, we demonstrated that AT(2) receptor stimulation
      attenuated TNFalpha-mediated NF-kappaB activation and MCP-1 expression. A
      tyrosine phosphatase inhibitor, orthovanadate, attenuated the AT(2) receptor
      mediated increase in IkappaB protein. Moreover, we observed that two IkappaB
      subunits (IkappaBalpha and IkappaBbeta) were tyrosine-phosphorylated after Ang II
      stimulation. Transfection of a dominant-negative Src homology protein tyrosine
      phosphatase-1 mutant into vascular smooth muscle cells inhibited the AT(2)
      receptor-mediated increase in IkappaB, leading to a significant increase in AT(1)
      receptor-induced NF-kappaB activation and MCP-1 expression. Taken together, our
      results demonstrated that AT(2) receptor stimulation attenuated MCP-1 expression
      via IkappaB stabilization, and Src homology protein tyrosine phosphatase-1 might
      play a critical role in the transcriptional regulation of MCP-1 expression
      through the control of IkappaB protein stability.

PMID- 14684845
TI  - Distinct regulation of internalization and mitogen-activated protein kinase
      activation by two isoforms of the dopamine D2 receptor.
AB  - Two isoforms of the dopamine D2 receptor, D2L (long) and D2S (short), differ by
      the insertion of a 29-amino acid specific to D2L within the putative third
      intracellular loop of the receptor. Here, we examined D2 receptor-mediated MAPK
      activation in association with receptor internalization. Overexpression of beta
      arrestin 1 and 2 increased the D2S-mediated activation of MAPK, whereas it did
      not affect the activation of MAPK by D2L. Expression of a dominant negative beta
      arrestin 2 (319-418) mutant and of a dominant negative dynamin I (K44A) mutant
      inhibited the activation of MAPK by D2S, but not the activation of MAPK by D2L.
      Treatment with inhibitors of internalization, i.e. concanavalin A and
      monodansylcadaverin, blocked D2S-mediated MAPK activation but not D2L-mediated
      activation. By confocal microscopy, we observed beta-arrestin 1 and 2,
      translocated to the plasma membrane and colocalized with D2L and D2S receptors
      upon stimulation with dopamine, and this was followed by the translocation of
      receptors into endocytic vesicles. Moreover, the expression of the beta-arrestin
      2 (319-418) mutant blocked the internalization of both D2L and D2S. In addition,
      although K44A dynamin mutant expression did not alter D2L internalization, it
      completely blocked the internalization of D2S. The stimulation of D2L induces
      activation of MAPK via transactivation of the platelet-derived growth factor
      receptor, whereas D2S does not. Taken together, these data suggest that D2L
      activates MAPK signaling by mobilizing the growth factor receptor, platelet
      derived growth factor receptor, whereas D2S appears to activate MAPK signaling by
      mobilizing clathrin-mediated endocytosis in a beta-arrestin/dynamin-dependent
      manner.

PMID- 14684846
TI  - Increased cytochrome P450 17alpha-hydroxylase promoter function in theca cells
      isolated from patients with polycystic ovary syndrome involves nuclear factor-1.
AB  - Cytochrome P450 17alpha-hydroxylase (CYP17) gene expression and androgen
      biosynthesis are persistently elevated in theca cells isolated from ovaries of
      women with polycystic ovary syndrome (PCOS). We previously reported that -235 to 
      109 bp of the CYP17 promoter confers increased CYP17 promoter function in PCOS
      theca cells. In this report, additional deletion and mutational analyses of the
      CYP17 promoter were performed to identify the sequences that contribute to
      increased CYP17 promoter function in PCOS theca cells. Results of these analyses
      established that augmented promoter function in PCOS theca cells results from
      preferentially increased basal regulation conferred by sequences between -188 and
      -147 bp of the CYP17 promoter. Scanning mutant analysis demonstrated that
      mutations within a 16-bp sequence, spanning -174 to -158 bp of the promoter,
      ablated increased basal CYP17 promoter function in PCOS theca cells. EMSA
      analysis demonstrated that the NF-1 family member, NF-1C, bound this sequence.
      Cotransfection of several NF-1C isoforms expressed in normal and PCOS cells
      repressed CYP17 promoter function. NF-1C protein and DNA binding were reduced in
      PCOS theca cell nuclear extracts, as compared with normal. Another NF-1C site
      between -102 and -90 bp of the promoter was also identified. However, mutation of
      this site had no effect on differential promoter function in PCOS theca cells.
      These studies demonstrate that 1) augmented CYP17 promoter function in PCOS theca
      cells results from increased basal regulation, and 2) diminished NF-1C-dependent
      repression may be one mechanism underlying increased basal CYP17 promoter
      activity and altered gene expression in PCOS theca cells.

PMID- 14684847
TI  - Fos and Jun inhibit estrogen-induced transcription of the human progesterone
      receptor gene through an activator protein-1 site.
AB  - The progesterone receptor (PR) gene is activated by estrogen in normal
      reproductive tissues and in MCF-7 human breast cancer cells. Although it is
      typically thought that estrogen responsiveness is mediated through estrogen
      response elements (EREs), the human PR gene lacks a palindromic ERE sequence. We
      have identified an activating protein-1 (AP-1) site at +745 in the human PR gene
      that bound purified Fos and Jun and formed a complex with Fos/Jun heterodimers
      present in MCF-7 nuclear extracts. Surprisingly, mutating the +745 AP-1 site in
      the context of a 1.5-kb region of the PR gene significantly enhanced estrogen
      receptor (ER) alpha-mediated transactivation, suggesting that the wild-type +745
      AP-1 site plays a role in inhibiting PR gene expression in the presence of
      hormone. In support of this idea, transient transfection assays demonstrated that
      increasing levels of Fos and Jun repressed transcription of a reporter plasmid
      containing the +745 AP-1 site. Fos levels were transiently increased, ERalpha
      levels were decreased, and Jun was dephosphorylated after MCF-7 cells were
      treated with estrogen. Chromatin immunoprecipitation assays demonstrated that Jun
      was associated with the +745 AP-1 site in the endogenous PR gene in the presence
      and in the absence of estrogen, but that ERalpha and Fos were only associated
      with the +745 AP-1 site after estrogen treatment of MCF-7 cells. Our studies
      suggest that the human PR gene is regulated by multiple transcription factors and
      that the differential binding of these dynamically regulated trans-acting factors
      influences gene expression.

PMID- 14684848
TI  - Sexual dimorphism of rat liver gene expression: regulatory role of growth hormone
      revealed by deoxyribonucleic Acid microarray analysis.
AB  - GH has diverse physiological actions and regulates the tissue-specific expression
      of numerous genes involved in growth, metabolism, and differentiation. Several of
      the effects of GH on somatic growth and gene expression are sex dependent and are
      regulated by pituitary GH secretory patterns, which are sexually differentiated.
      The resultant sex differences in plasma GH profiles are particularly striking in
      rodents and are the major determinant of sex differences in pubertal body growth
      rates and the expression in liver of several cytochrome P450 (CYP) enzymes that
      metabolize steroids, drugs, and environmental chemicals of importance to
      endocrinology, pharmacology, and toxicology. DNA microarray analysis was used to
      identify rat liver-expressed genes that show sexual dimorphism, and to ascertain
      the role of GH as a regulator of their sexually dimorphic expression. Adult male
      and female rats were untreated or were treated with GH by 7-d continuous infusion
      using an Alzet osmotic minipump. Poly(A) RNA was purified from individual livers
      and Cy3- and Cy5-labeled cDNA probes cohybridized to Pan Rat Liver and 5K Rat
      Oligonucleotide microarrays representing 5889 unique rat genes. Analysis of
      differential gene expression profiles identified 37 liver-expressed, female
      predominant genes; of these, 27 (73%) were induced by continuous GH treatment of
      male rats. Moreover, only three of 30 genes up-regulated in male rat liver by
      continuous GH treatment did not display female-dominant expression. Further
      analysis revealed that 44 of 49 male-predominant genes (90%) were down-regulated
      in the livers of continuous GH-treated male rats compared with untreated male
      rats, whereas only five of 49 genes that were down-regulated in male rats by
      continuous GH treatment were not male dominant in their expression. Real-time PCR
      analysis applied to a sampling of 10 of the sexually dimorphic genes identified
      in the microarray analysis verified their sex- and GH-dependent patterns of
      regulation. Taken together, these studies establish that GH-regulated gene
      expression is the major mechanistic determinant of sexually dimorphic gene
      expression in the rat liver model.

PMID- 14684849
TI  - Transient, ligand-dependent arrest of the androgen receptor in subnuclear foci
      alters phosphorylation and coactivator interactions.
AB  - Here we report that mutations within the DNA-binding domain of AR, shown
      previously to inhibit nuclear export to the cytoplasm, cause an androgen
      dependent defect in intranuclear trafficking of AR. Mutation of two conserved
      phenylalanines within the DNA recognition helix (F582, 583A) results in androgen
      dependent arrest of AR in multiple subnuclear foci. A point mutation in one of
      the conserved phenylalanines (DeltaF582, F582Y) is known to cause androgen
      insensitivity syndrome (AIS). Both AIS mutants (DeltaF582, F582Y) and the export
      mutant (F582, 583A) displayed androgen-dependent arrest in foci, and all three
      mutants promoted androgen-dependent accumulation of the histone acetyl
      transferase CREB binding protein (CBP) in the foci. The foci correspond to a
      subnuclear compartment that is highly enriched for the steroid receptor
      coactivator glucocorticoid receptor-interacting protein (GRIP)-1. Agonist-bound
      wild-type AR induces the redistribution of GRIP-1 from foci to the nucleoplasm.
      This likely reflects a direct interaction between these proteins because mutation
      of a conserved residue within the major coactivator binding site on AR (K720A)
      inhibits AR-dependent dissociation of GRIP-1 from foci. GRIP-1 also remains foci
      associated in the presence of agonist-bound F582, 583A, DeltaF582, or F582Y forms
      of AR. Two-dimensional phospho-peptide mapping and analysis with a phospho
      specific antibody revealed that mutant forms of AR that arrest in the subnuclear
      foci are hypophosphorylated at Ser81, a site that normally undergoes androgen
      dependent phosphorylation. Our working model is that the subnuclear foci are
      sites where AR undergoes ligand-dependent engagement with GRIP-1 and CBP, a
      recruitment step that occurs before Ser81 phosphorylation and association with
      promoters of target genes.

PMID- 14684850
TI  - The EZC-prostate model: noninvasive prostate imaging in living mice.
AB  - Recently, progress in the development of prostate-specific promoters and high
      resolution imaging techniques has made real-time monitoring of transgenic
      expression possible, opening a vista of potentially important in vivo models of
      prostate disease. Herein, we describe a novel prostate reporter model, called the
      EZC-prostate model that permits both ex vivo and in vivo imaging of the prostate
      using a sensitive charge-coupled device. Firefly luciferase and enhanced green
      fluorescent protein were targeted to the prostate epithelium using the composite
      human kallikrein 2 (hK2)-based promoter, hK2-E3/P. In EZC-prostate mice, the
      ventral and dorsal/lateral prostate lobes were brilliant green under fluorescence
      microscopy, with expression localized to the secretory epithelium. In contrast,
      enhanced green fluorescent protein was undetectable in the anterior lobes of
      prostate, seminal vesicles, testes, liver, lung, and brain. The kinetics of
      luciferase activity in intact and castrated living mice monitored with the IVIS
      charge-coupled device-based imaging system confirmed that firefly luciferase
      expression was largely prostate restricted, increased with age up to 24 wk, and
      was androgen dependent. Decreases in reporter expression after 24 wk may reflect
      well known, age-related decreases in androgen signaling with age in humans. Ex
      vivo imaging of microdissected animals further confirmed that the luminescence
      detected in living mice emanated predominately from the prostate, with minor
      signals originating from the testes and cecum. These data demonstrate that the
      hK2-E3/P promoter directs strong prostate-specific expression in a transgenic
      mouse model. Multigenic models, generated by crosses with various hyperplastic
      and neoplastic prostate disease models, could potentially provide powerful new
      tools in longitudinal monitoring of changes in prostate size, androgen signaling,
      metastases, or response to novel therapies without sacrificing large cohorts of
      animals.

PMID- 14684851
TI  - Mutually antagonistic effects of androgen and activin in the regulation of
      prostate cancer cell growth.
AB  - Activin, a member of the TGFbeta superfamily, is expressed in the prostate and
      inhibits growth. We demonstrate that the effects of activin and androgen on
      regulation of prostate cancer cell growth are mutually antagonistic. In the
      absence of androgen, activin induced apoptosis in the androgen-dependent human
      prostate cancer cell line LNCaP, an effect suppressed by androgen administration.
      Although activin by itself did not alter the cell cycle distribution, it potently
      suppressed androgen- induced progression of cells into S-phase of the cell cycle
      and thus inhibited androgen-stimulated growth of LNCaP cells. Expression changes
      in cell cycle regulatory proteins such as Rb, E2F-1, and p27 demonstrated a
      strong correlation with the mutually antagonistic growth regulatory effects of
      activin and androgen. The inhibitory effect of activin on growth was independent
      of serine, serine, valine, serine motif phosphorylation of Smad3. Despite their
      antagonistic effect on growth, activin and androgen costimulated the expression
      of prostate-specific antigen through a Smad3-mediated mechanism. These
      observations indicate the existence of a complex cross talk between activin and
      androgen signaling in regulation of gene expression and growth of the prostate.

PMID- 14684852
TI  - Growth differentiation factor-9 signaling is mediated by the type I receptor,
      activin receptor-like kinase 5.
AB  - Growth differentiation factor-9 (GDF-9) is an oocyte-derived growth factor and a
      member of the TGF-beta superfamily that includes TGF-beta, activin, and bone
      morphogenetic proteins (BMPs). GDF-9 is indispensable for the development of
      ovarian follicles from the primary stage, and treatment with GDF-9 enhances the
      progression of early follicles into small preantral follicles. Similar to other
      TGF-beta family ligands, GDF-9 likely initiates signaling mediated by type I and
      type II receptors with serine/threonine kinase activity, followed by the
      phosphorylation of intracellular transcription factors named Smads. We have shown
      previously that GDF-9 interacts with the BMP type II receptor (BMPRII) in
      granulosa cells, but the type I receptor involved is unknown. Using P19 cells, we
      now report that GDF-9 treatment stimulated the CAGA-luciferase reporter known to
      be responsive to TGF-beta mediated by the type I receptor, activin receptor-like
      kinase (ALK)5. In contrast, GDF-9 did not stimulate BMP-responsive reporters. In
      addition, treatment with GDF-9 induced the phosphorylation of Smad2 and Smad3 in
      P19 cells, and the stimulatory effect of GDF-9 on the CAGA-luciferase reporter
      was blocked by the inhibitory Smad7, but not Smad6. We further reconstructed the
      GDF-9 signaling pathway using Cos7 cells that are not responsive to GDF-9. After
      overexpression of ALK5, with or without exogenous Smad3, the Cos7 cells gained
      GDF-9 responsiveness based on the CAGA-luciferase reporter assay. The roles of
      ALK5 and downstream pathway genes in mediating GDF-9 actions were further tested
      in ovarian cells. In cultured rat granulosa cells from early antral follicles,
      treatment with GDF-9 stimulated the CAGA-luciferase reporter activity and induced
      the phosphorylation of Smad3. Furthermore, transfection with small interfering
      RNA for ALK5 or overexpression of the inhibitory Smad7 resulted in dose-dependent
      suppression of GDF-9 actions. In conclusion, although GDF-9 binds to the BMP
      activated type II receptor, its downstream actions are mediated by the type I
      receptor, ALK5, and the Smad2 and Smad3 proteins. Because ALK5 is a known
      receptor for TGF-beta, diverse members of the TGF-beta family of ligands appear
      to interact with a limited number of receptors in a combinatorial manner to
      activate two downstream Smad pathways.

PMID- 14684853
TI  - Naturalistic auditory contrast improves spectrotemporal coding in the cat
      inferior colliculus.
AB  - Statistical analysis of natural sounds and speech reveals logarithmically
      distributed spectrotemporal modulations that can cover several orders of
      magnitude. By contrast, most artificial stimuli used to probe auditory function,
      including pure tones and white noise, have linearly distributed amplitude
      fluctuations with a limited average dynamic range. Here we explore whether the
      operating range of the auditory system is physically matched to the statistical
      structure of natural sounds. We recorded single-unit and multi-unit neuronal
      activity from the central nucleus of the cat inferior colliculus (ICC) in
      response to dynamic spectrotemporal sound sequences to determine whether ICC
      neurons respond preferentially to linear or logarithmic spectrotemporal
      amplitudes. We varied the intensity, dynamic range, and contrast statistics of
      these sounds to mimic those of natural and artificial stimuli. ICC neurons
      exhibited monotonic and nonmonotonic contrast dependencies with increasing
      dynamic range that were independent of the stimulus intensity. Midbrain neurons
      had higher firing rates and higher receptive field energies and showed a net
      improvement in spectrotemporal encoding ability for logarithmic stimuli, with an
      increase in the mutual information rate of approximately 50% over linear
      amplitude sounds. This efficient use of logarithmic spectrotemporal modulations
      by auditory midbrain neurons reflects a neural adaptation to structural
      regularities in natural sounds and likely underlies human perceptual abilities.

PMID- 14684854
TI  - Seizure-induced changes in place cell physiology: relationship to spatial memory.
AB  - Status epilepticus (SE) is a frequent neurological emergency associated with a
      significant risk of morbidity in survivors. Impairment of hippocampal-specific
      memory is a common and serious deficit occurring in many of the survivors.
      However, the pathophysiological basis of cognitive deficits after SE is not
      clear. To directly address the cellular concomitants of spatial memory
      impairment, we recorded the activity of place cells from CA1 in freely moving
      rats subjected to SE during early development and compared this activity to that
      in control rats. Place cells discharge rapidly only when the rat's head is in a
      cell-specific part of the environment called the "firing field." This firing
      field remains stable over time. Normal place cell function seems to be essential
      for stable spatial memory for the environment. We, therefore, compared place cell
      firing patterns with visual-spatial memory in the water maze in SE and control
      rats. Compared with controls, place cells from the SE rats were less precise and
      less stable. Concordantly, the water maze performance was also impaired. There
      was a close relationship between precision and stability of place cells and water
      maze performance. In contrast, a single, acute, chemically induced seizure
      produced cessation of place cell activity and spatial memory impairment in water
      maze performance that reversed within 24 hr. These results strongly bolster the
      idea that there is a relationship between abnormal place cells and spatial
      memory. Our findings also suggest that the defects in place cell and spatial
      memory after SE and acute chemically induced seizures result from different
      processes.

PMID- 14684855
TI  - Functional asymmetry for auditory processing in human primary auditory cortex.
AB  - Structural asymmetries in the supratemporal plane of the human brain are often
      cited as the anatomical basis for the lateralization of language predominantly to
      the left hemisphere. However, similar asymmetries are found for structures
      mediating earlier events in the auditory processing stream, suggesting that
      functional lateralization may occur even at the level of primary auditory cortex.
      We tested this hypothesis using functional magnetic resonance imaging to evaluate
      human auditory cortex responses to monaurally presented tones. Relative to
      silence, tones presented separately to either ear produced greater activation in
      left than right Heschl's gyrus, the location of primary auditory cortex. This
      functional lateralization for primary auditory cortex is distinct from the
      contralateral dominance reported for other mammals, including nonhuman primates,
      and may have contributed to the evolution of a unique role for the left
      hemisphere in language processing.

PMID- 14684856
TI  - Interaxonal Eph-ephrin signaling may mediate sorting of olfactory sensory axons
      in Manduca sexta.
AB  - We have investigated possible roles of the Eph family receptor tyrosine kinases
      and their ligand ephrins in the developing primary olfactory nerve pathway in the
      moth Manduca sexta. The Manduca homologs of the Eph receptor (MsEph) and ephrin
      ligand (MsEphrin) are most closely related to Drosophila Eph and ephrin,
      respectively. In situ labeling with Fc-fusion probes, in which IgG Fc was linked
      to the extracellular domain of MsEph (Eph-Fc) or MsEphrin (ephrin-Fc), reveals
      that both Eph receptors and ephrins are expressed on axons of olfactory receptor
      cells (ORCs) during their ingrowth to the primary center, the antennal lobe (AL).
      Interestingly, Eph receptors and ephrins are differentially distributed among
      identifiable glomeruli such that glomeruli with high receptor staining show
      little or no ligand staining, and vice versa, suggesting a complementary Eph
      ephrin expression by subsets of ORC axons innervating a particular set of
      glomeruli. In contrast, neither Eph receptors nor ephrins are detectable in
      intrinsic components of the AL. In vitro, ephrin-Fc and Eph-Fc, when present
      homogeneously in the substratum, inhibit neurite outgrowth from olfactory
      epithelial explants. Moreover, in patterned substratum, neurites growing on the
      standard substratum turn or stop after encountering the test substratum
      containing ephrin-Fc. These in vitro observations indicate that MsEphrin can act
      as an inhibitor/repulsive cue for ORC axons. Based on results from in situ and in
      vitro experiments, we hypothesize that Eph receptors and ephrins mediate axon
      sorting and fasciculation through repulsive axon-axon interactions.

PMID- 14684857
TI  - Synergy, redundancy, and independence in population codes.
AB  - A key issue in understanding the neural code for an ensemble of neurons is the
      nature and strength of correlations between neurons and how these correlations
      are related to the stimulus. The issue is complicated by the fact that there is
      not a single notion of independence or lack of correlation. We distinguish three
      kinds: (1) activity independence; (2) conditional independence; and (3)
      information independence. Each notion is related to an information measure: the
      information between cells, the information between cells given the stimulus, and
      the synergy of cells about the stimulus, respectively. We show that these
      measures form an interrelated framework for evaluating contributions of signal
      and noise correlations to the joint information conveyed about the stimulus and
      that at least two of the three measures must be calculated to characterize a
      population code. This framework is compared with others recently proposed in the
      literature. In addition, we distinguish questions about how information is
      encoded by a population of neurons from how that information can be decoded.
      Although information theory is natural and powerful for questions of encoding, it
      is not sufficient for characterizing the process of decoding. Decoding
      fundamentally requires an error measure that quantifies the importance of the
      deviations of estimated stimuli from actual stimuli. Because there is no a priori
      choice of error measure, questions about decoding cannot be put on the same level
      of generality as for encoding.

PMID- 14684858
TI  - Assembly of alpha4beta2 nicotinic acetylcholine receptors assessed with
      functional fluorescently labeled subunits: effects of localization, trafficking,
      and nicotine-induced upregulation in clonal mammalian cells and in cultured
      midbrain neurons.
AB  - Fura-2 recording of Ca2+ influx was used to show that incubation in 1 microm
      nicotine (2-6 d) upregulates several pharmacological components of acetylcholine
      (ACh) responses in ventral midbrain cultures, including a MLA-resistant, DHbetaE
      sensitive component that presumably corresponds to alpha4beta2 receptors. To
      study changes in alpha4beta2 receptor levels and assembly during this
      upregulation, we incorporated yellow and cyan fluorescent proteins (YFPs and
      CFPs) into the alpha4 or beta2 M3-M4 intracellular loops, and these subunits were
      coexpressed in human embryonic kidney (HEK) 293T cells and cultured ventral
      midbrain neurons. The fluorescent receptors resembled wild-type receptors in
      maximal responses to ACh, dose-response relations, ACh-induced Ca2+ influx, and
      somatic and dendritic distribution. Transfected midbrain neurons that were
      exposed to nicotine (1 d) displayed greater levels of fluorescent alpha4 and
      beta2 nicotinic ACh receptor (nAChR) subunits. As expected from the hetero
      multimeric nature of alpha4beta2 receptors, coexpression of the alpha4-YFP and
      beta2-CFP subunits resulted in robust fluorescence resonance energy transfer
      (FRET), with a FRET efficiency of 22%. In midbrain neurons, dendritic alpha4beta2
      nAChRs displayed greater FRET than receptors inside the soma, and in HEK293T
      cells, a similar increase was noted for receptors that were translocated to the
      surface during PKC stimulation. When cultured transfected midbrain neurons were
      incubated in 1 microm nicotine, there was increased FRET in the cell body,
      denoting increased assembly of alpha4beta2 receptors. Thus, changes in
      alpha4beta2 receptor assembly play a role in the regulation of alpha4beta2 levels
      and responses in both clonal cell lines and midbrain neurons, and the regulation
      may result from Ca2+-stimulated pathways.

PMID- 14684859
TI  - Functional specialization of male and female vocal motoneurons.
AB  - Vocal behaviors of African clawed frogs (Xenopus laevis) are produced by a single
      pair of muscles. This simplification, relative to other vertebrates, allows us to
      more easily determine how CNS motor pathways function to produce sex-specific
      songs. We describe here certain sexually differentiated properties of vocal
      motoneurons that are matched to male and female vocal demands. Both active and
      passive membrane properties differ between the sexes. Male motoneurons have lower
      input resistances and larger membrane capacitances than female motoneurons. Two
      distinct firing patterns are found, in different proportions, in males and
      females. The strongly adapting neurons that predominate in males initiate spikes
      at short, reliable latencies, whereas the weakly adapting motoneurons
      characteristic of females translate graded levels of depolarization into
      different firing rates. Low-threshold potassium currents (IKL) predominate in
      males. Hyperpolarization-activated cationic currents (IH) are found almost
      exclusively in males. Modeling results indicate that sex-typical active and
      passive properties can account for the occurrence of strongly and weakly adapting
      spike trains in the sexes. In particular, IKL seem to play an important role in
      determining the firing patterns of neurons. We suggest that these physiological
      differences facilitate transformation of synaptic inputs into male- and female
      specific outputs that generate sexually distinct songs in vivo.

PMID- 14684860
TI  - Cortical representation of bimanual movements.
AB  - It is well established that the discharge of neurons in primate motor cortex is
      tuned to the movement direction of the contralateral arm. Interestingly, it has
      been found that these neurons exhibit a directional tuning to the ipsilateral arm
      as well and that the preferred directions to both arms tend to be similar. A
      recent study showed that motor cortex cells are also directionally selective to
      bimanual movements, but the relationship between the bimanual and unimanual
      representations remains unclear. To address this issue, we analyzed the responses
      of motor cortical neurons recorded from two macaque monkeys during unimanual and
      bimanual reaching movements. We decomposed the bimanual movement representation
      into contralateral and ipsilateral directionally tuned components. Our major
      finding is that the movement of the contralateral arm modifies the tuning of the
      cells to the ipsilateral arm such that: (1) the offset and modulation depth of
      the tuning are suppressed; and (2) the preferred directions are randomly shifted.
      Both these effects eliminate the correlation between the contralateral and
      ipsilateral representations during bimanual movements. We suggest that the
      modification of the ipsilateral arm representation is caused by the recruitment
      of local inhibition that conveys callosal inputs during bimanual movements. This
      hypothesis is supported by the analysis of a model of two motor cortical
      networks, coupled with sparse random interhemispheric projections that reproduce
      the main features observed in the data. Finally, we show that the modification of
      the ipsilateral arm representation reduces the interference between the movements
      of both arms.

PMID- 14684861
TI  - Generation of functional radial glial cells by embryonic and adult forebrain
      neural stem cells.
AB  - Radial glial cells (RGCs), a transient cell population present only in the
      developing CNS, function both as precursor cells and as scaffolds to support
      neuron migration. Their cellular origin, however, is not understood. In the
      present study, we tested the hypothesis that functional RGCs can be generated by
      multipotent neural stem cells. Embryonic forebrain neural stem cells were studied
      in vitro to identify putative signals that promote the generation and
      differentiation of functional RGCs, determined by their ability to support
      neuronal migration. Epidermal growth factor receptor signaling was sufficient to
      regulate both the generation and differentiation of morphologically,
      antigenically, and functionally defined RGCs. In contrast, fibroblast growth
      factor-2 promoted the generation of RGCs but was unable to support their
      differentiation. Although RGCs are not normally present in the adult brain,
      epidermal growth factor stimulated adult forebrain neural stem cells to generate
      RGCs in vitro and functional RGCs within the adult forebrain subependyma in vivo.
      Surprisingly, epidermal growth factor receptor signaling also promoted adult
      forebrain ependymal cells to dedifferentiate and adopt a radial morphology in
      vivo. These results suggest that neural stem cells can give rise to RGCs and that
      RGC-guided neuronal migration can be recapitulated in the adult CNS.

PMID- 14684862
TI  - Delayed secondary phase of peri-infarct depolarizations after focal cerebral
      ischemia: relation to infarct growth and neuroprotection.
AB  - In focal cerebral ischemia, peri-infarct depolarizations (PIDs) cause an
      expansion of core-infarcted tissue into adjacent penumbral regions of reversible
      injury and have been shown to occur through 6 hr after injury. However, infarct
      maturation proceeds through 24 hr. Therefore, we studied PID occurrence through
      72 hr after both transient and permanent middle cerebral artery occlusion (MCAo)
      via continuous DC recordings in nonanesthetized rats. PIDs occurred an average 13
      times before reperfusion at 2 hr and then ceased for an average approximately 8
      hr. After this quiescent period, PID activity re-emerged in a secondary phase,
      which reached peak incidence at 13 hr and consisted of a mean 52 PIDs over 2-24
      hr. This phase corresponded to the period of infarct maturation; rates of infarct
      growth through 24 hr coincided with changes in PID frequency and peaked at 13 hr.
      In permanent MCAo, PIDs also occurred in a biphasic pattern with a mean of 78
      events over 2-24 hr. Parameters of secondary phase PID incidence correlated with
      infarct volumes in transient and permanent ischemia models. The role of secondary
      phase PIDs in infarct development was further investigated in transient MCAo by
      treating rats with a high-affinity NMDA receptor antagonist at 8 hr after injury,
      which reduced post-treatment PID incidence by 57% and provided 37%
      neuroprotection. Topographic mapping with multielectrode recordings revealed
      multiple sources of PID initiation and patterns of propagation. These results
      suggest that PIDs contribute to the recruitment of penumbral tissue into the
      infarct core even after the restoration of blood flow and throughout the period
      of infarct maturation.

PMID- 14684863
TI  - Synaptic augmentation contributes to environment-driven regulation of the aplysia
      siphon-withdrawal reflex.
AB  - This research shows that short-term synaptic plasticity can play a critical role
      in shaping the behavioral response to environmental change. In Aplysia, exposure
      to turbulent environments produces a stable reduction in the duration of the
      siphon-withdrawal reflex (SWR) and the responsiveness of siphon motor neurons.
      Recovery takes >1 min after a brief (10 sec-5 min) exposure but <1 min after a
      long (10 min) exposure. Here we demonstrate that (1) in-turbulence and post
      turbulence phases of regulation depend on different cellular processes and (2)
      the post-turbulence phase of regulation is mediated by augmentation (AUG), an
      activity-dependent form of short-term synaptic plasticity. In reduced
      preparations (tail, siphon, and CNS), we show that treatment with 100 microm d
      tubocurarine has no effect on in-turbulence regulation but blocks up to 90% of
      post-turbulence regulation, indicating that these phases of regulation are
      mediated by distinct cellular process. We then show that (1) turbulence induces
      activity in L30 inhibitory interneurons, (2) this activation produces AUG that
      lasts 1 min after a brief exposure to turbulence, and (3) manipulations that
      attenuate L30 AUG also attenuate regulation after brief turbulence. We also found
      that long (10 min) exposures to turbulence do not produce a post-turbulence phase
      of regulation because L30 activity declines over the course of a long turbulence
      exposure, leading to the decay of AUG before turbulence offset. Our results
      demonstrate a specific behavioral function of AUG and show how interactions
      between cellular processes can confer temporal sensitivity in the network
      regulation of behavior.

PMID- 14684864
TI  - Human cerebral activation during steady-state visual-evoked responses.
AB  - Flicker stimuli of variable frequency (2-90 Hz) elicit a steady-state visual
      evoked response (SSVER) in the electroencephalogram (EEG) with the same frequency
      as the stimulus. In humans, the amplitude of this response peaks at approximately
      15 Hz, decreasing at higher stimulation frequencies. It was not known whether
      this peak response corresponds to increased synaptic activity in the visual
      cortex or to other mechanisms [for instance, the temporal coherence (phase
      summation) of evoked responses]. We studied the SSVER in 16 normal volunteers by
      means of visual stimulation at 14 different frequencies (from 5 to 60 Hz) while
      recording the EEG. In nine subjects of the group, we measured regional cerebral
      blood flow (rCBF) with positron emission tomography (PET)-H2(15)O at rest and
      during visual stimulation at five different frequencies: 5, 10, 15, 25, and 40
      Hz. We confirmed that the amplitude of the SSVER in occipital regions peaks at 15
      Hz stimulation. Applying to the PET rCBF data a contrast weighted by the
      amplitude of the SSVER, we determined that the primary visual cortex rCBF follows
      an activation pattern similar to the SSVER. This finding suggests that the
      amplitude of the SSVER corresponds to increased synaptic activity, specifically
      in Brodmann's area 17. Additionally, this study showed that visual stimulation at
      40 Hz causes selective activation of the macular region of the visual cortex, and
      that a region in the dorsal aspect of the Crus I lobule of the left cerebellar
      hemisphere is activated during repetitive visual stimulation.

PMID- 14684865
TI  - How spike generation mechanisms determine the neuronal response to fluctuating
      inputs.
AB  - This study examines the ability of neurons to track temporally varying inputs,
      namely by investigating how the instantaneous firing rate of a neuron is
      modulated by a noisy input with a small sinusoidal component with frequency (f).
      Using numerical simulations of conductance-based neurons and analytical
      calculations of one-variable nonlinear integrate-and-fire neurons, we
      characterized the dependence of this modulation on f. For sufficiently high
      noise, the neuron acts as a low-pass filter. The modulation amplitude is
      approximately constant for frequencies up to a cutoff frequency, fc, after which
      it decays. The cutoff frequency increases almost linearly with the firing rate.
      For higher frequencies, the modulation amplitude decays as C/falpha, where the
      power alpha depends on the spike initiation mechanism. For conductance-based
      models, alpha = 1, and the prefactor C depends solely on the average firing rate
      and a spike "slope factor," which determines the sharpness of the spike
      initiation. These results are attributable to the fact that near threshold, the
      sodium activation variable can be approximated by an exponential function. Using
      this feature, we propose a simplified one-variable model, the "exponential
      integrate-and-fire neuron," as an approximation of a conductance-based model. We
      show that this model reproduces the dynamics of a simple conductance-based model
      extremely well. Our study shows how an intrinsic neuronal property (the
      characteristics of fast sodium channels) determines the speed with which neurons
      can track changes in input.

PMID- 14684866
TI  - Hippocampal excitability increases during the estrous cycle in the rat: a
      potential role for brain-derived neurotrophic factor.
AB  - To test the hypothesis that induction of BDNF may contribute to changes in
      hippocampal excitability occurring during the female reproductive cycle, we
      examined the distribution of BDNF immunoreactivity and changes in CA1 and CA3
      electrophysiology across the estrous cycle in rats. Hippocampal BDNF
      immunoreactivity increased on the day of proestrus as well as on the following
      morning (estrus), relative to metestrus or ovariectomized animals. Changes in
      immunoreactivity were clearest in mossy fiber axons of dentate gyrus granule
      cells, which contain the highest concentration of BDNF. Increased
      immunoreactivity was also apparent in the neuropil-containing dendrites of CA1
      and CA3 neurons. Electrophysiological recordings in hippocampal slices showed
      robust cycle-dependent differences. Evoked responses of CA1 neurons to Schaffer
      collateral stimulation changed over the cycle, with larger maximum responses at
      both proestrus and estrus relative to metestrus. In area CA3, repetitive hilar
      stimuli frequently evoked multiple population spikes at proestrus and estrus but
      only rarely at other cycle stages, and never in slices of ovariectomized rats.
      Hyperexcitability in area CA3 at proestrus was blocked by exposure to the high
      affinity neurotrophin receptor antagonist K252a, or an antagonist of the alpha7
      nicotinic cholinergic receptor, whereas it was induced at metestrus by the
      addition of BDNF to hippocampal slices. These studies suggest that hippocampal
      BDNF levels change across the estrous cycle, accompanied by neurophysiological
      responses that resemble the effects of BDNF treatment. An estrogen-induced
      interaction of BDNF and alpha7 nicotinic receptors on mossy fibers seems
      responsible for estrous cycle changes in area CA3. Periovulatory changes in
      hippocampal function may, thus, involve estrogen-induced increases in BDNF
      expression.

PMID- 14684867
TI  - Neuronal induction of the immunoproteasome in Huntington's disease.
AB  - Huntington's disease (HD) inclusions are stained with anti-ubiquitin and anti
      proteasome antibodies. This, together with proteasome activity studies on
      transfected cells, suggest that an impairment of the ubiquitin-proteasome system
      (UPS) may be key in HD pathogenesis. To test whether proteasome activity is
      impaired in vivo, we performed enzymatic assays for the three peptidase
      activities of the proteasome in brain extracts from the HD94 conditional mouse
      model of HD. We found no inhibition of any of the activities, suggesting that if
      UPS impairment happens in vivo, it is not at the level of the proteasome
      catalytic core. Intriguingly, the chymotrypsin- and trypsin-like activities
      increased selectively in the affected and aggregate-containing regions: cortex
      and striatum. Western blot analysis revealed no difference in total proteasome
      content whereas an increase in the interferon-inducible subunits of the
      immunoproteasome, LMP2 and LMP7, was observed. These subunits confer to the
      proteasome catalytic properties that are optimal for MHC-I peptide presentation.
      Immunohistochemistry in control mouse brain revealed LMP2 and LMP7 mainly in
      neurons. Accordingly, their increase in HD94 mice predominantly took place in
      neurons, and 5% of the ubiquitin-positive cortical aggregates were also LMP2
      positive. Ultrastructural analysis of neurons with high level of immunoproteasome
      subunits revealed signs of neurodegeneration like nuclear indentation or
      fragmentation and dark cell appearance. The neuronal induction of LMP2 and LMP7
      and the associated signs of neurodegeneration were also found in HD postmortem
      brains. Our results indicate that LMP2 and LMP7 participate in normal neuronal
      physiology and suggest a role in HD neurodegeneration.

PMID- 14684868
TI  - Dopamine D4 receptor-induced postsynaptic inhibition of GABAergic currents in
      mouse globus pallidus neurons.
AB  - Dopamine D4 receptors (D4R) are localized in the globus pallidus (GP), but their
      function remains unknown. In contrast, dopamine D2 receptor activation
      hyperpolarizes medium spiny neurons projecting from the striatum to the GP and
      inhibits GABA release. However, using slice preparations from D2R-deficient [D2
      knock-out (D2KO)] mice, we found that dopamine inhibited GABA(A)-receptor
      mediated currents in GP neurons. The paired-pulse ratio was statistically
      unchanged after dopamine application but was significantly elevated in D2KO wild
      type littermates (WT). Furthermore, in D2KO mice, outward currents elicited by
      iontophoretically applied GABA were suppressed by dopamine. Dopamine (30 microm)
      decreased the amplitude of miniature IPSCs in both WT and D2KO mice, but the
      decrease in the frequency was observed only in the former but not significantly
      in the latter. Dopamine-induced suppression of IPSCs was blocked by selective D4R
      antagonists (clozapine or 3-[4-(4-iodophenyl)piperazin-1-yl]methyl-1H-pyrrolo[2,3
      b]pyridine trihydrochloride), and a D4R-selective agonist N-[[4-(2-cyanophenyl)-1
      piperazinyl]methyl]-3-methyl-benzamide reversibly and dose-dependently suppressed
      IPSCs, whereas agonists [SKF38,393 ((+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3
      benzazepine-7,8-diol hydrochloride) or (+)-(4aR,10bR)-3,4,4a,10b-tetrahydro-4
      propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol] or antagonists [SCH23,390
      (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
      hydrochloride) or sulpiride] of other receptor subtypes had little effect. In GP
      neurons from D4R-deficient mice, dopamine-induced inhibition of GABAergic outward
      currents was undetectable. D4R activation suppressed the activity of protein
      kinase A in GP neurons, resulting in a decrease in the amplitude of GABAergic
      IPSCs. These findings showed that postsynaptic activation of D4R on the GP
      neurons reduces GABAergic currents through the suppression of PKA activity.

PMID- 14684869
TI  - Distribution of K+-dependent Na+/Ca2+ exchangers in the rat supraoptic
      magnocellular neuron is polarized to axon terminals.
AB  - Neurons are polarized into compartments such as the soma, dendrites, and axon
      terminals, each of which has highly specialized functions. To test whether Ca2+
      is differently handled in different compartments of a neuron, we investigated
      Ca2+ clearance mechanisms in somata of supraoptic magnocellular neurosecretory
      cells (MNCs) and in their axon terminals located in neurohypophyses. Using patch
      clamp and microfluorometry techniques, Ca2+ transients were evoked by
      depolarizing pulses. Endogenous Ca2+ binding ratios (kappaS) and Ca2+ clearance
      rates were calculated from the decay phases of Ca2+ transients according to the
      single compartment model. Mean values of kappaS were 79 +/- 2.6 in somata of MNCs
      and 187 +/- 19 in axon terminals. Ca2+ clearance rate in axon terminals, which
      were calculated from time derivative of Ca2+ decay and the kappaS values, were
      approximately threefold higher than in somata. In response to external Na+
      reduction, Ca2+ clearance rates were reduced by 65% in axon terminals, but did
      not change in somata. Immunohistochemical assays confirmed that K+-dependent
      Na+/Ca2+ exchanger (NCKX2) was specifically localized to neurohypophysial axon
      terminals and was not found in somata. In somata, inhibition of sarcoendoplasmic
      reticulum Ca2+-ATPase (SERCA) pumps, mitochondrial Ca2+-uniporter, and plasma
      membrane Ca2+-ATPase (PMCA) pumps decreased Ca2+ clearance rate by 48, 27, and
      21%, respectively. These results suggest that neurohypophysial axon terminals
      have greater Ca2+ clearance power than somata because of the specific
      localization of NCKX2, and that Ca2+ clearance in somata of MNCs is mediated by
      SERCA pumps, mitochondrial uniporter, and PMCA pumps.

PMID- 14684870
TI  - Slick (Slo2.1), a rapidly-gating sodium-activated potassium channel inhibited by
      ATP.
AB  - Neuronal stressors such as hypoxia and firing of action potentials at very high
      frequencies cause intracellular Na+ to rise and ATP to be consumed faster than it
      can be regenerated. We report the cloning of a gene encoding a K+ channel, Slick,
      and demonstrate that functionally it is a hybrid between two classes of K+
      channels, Na+-activated (KNa) and ATP-sensitive (KATP) K+ channels. The Slick
      channel is activated by intracellular Na+ and Cl- and is inhibited by
      intracellular ATP. Slick is widely expressed in the CNS and is detected in heart.
      We identify a consensus ATP binding site near the C terminus of the channel that
      is required for ATP and its nonhydrolyzable analogs to reduce open probability.
      The convergence of Na+, Cl-, and ATP sensitivity in one channel may endow Slick
      with the ability to integrate multiple indicators of the metabolic state of a
      cell and to adjust electrical activity appropriately.

PMID- 14684871
TI  - Tyrosinase expression during neuroblast divisions affects later pathfinding by
      retinal ganglion cells.
AB  - Occulocutaneous albinism is caused by mutations in the gene encoding the enzyme
      tyrosinase. Individuals with this disorder are predisposed to visual system
      deficits. We determined the critical period during development when tyrosinase
      expression is essential for the appropriate pathfinding of ganglion cell axons
      from the retina to the dorsal lateral geniculate nucleus. We used a line of mice
      with a Tyrosinase transgene, the expression of which is regulatable with the lac
      operator-repressor system, to restrict tyrosinase activity to discrete periods of
      embryogenesis. When tyrosinase was expressed throughout the period of neuroblast
      divisions that produce the ipsilaterally projecting ganglion cells, axonal
      projections innervated the same volume of the ipsilateral dorsal lateral
      geniculate nucleus of the thalamus as in normal mice. If tyrosinase expression
      ceased before the end of neuroblast divisions, or was not initiated until after
      they had begun, the degree of ipsilateral innervation was smaller, as in albino
      mice. Tyrosinase expression was not required during the entire period of
      pathfinding itself or during final maturation of the retinogeniculate pathway.
      Thus, tyrosinase appears to set up a signal early in visual system development
      that determines the pathway taken later by ganglion cell axons.

PMID- 14684872
TI  - Beta subunit phosphorylation selectively increases fast desensitization and
      prolongs deactivation of alpha1beta1gamma2L and alpha1beta3gamma2L GABA(A)
      receptor currents.
AB  - We studied the effects of phosphorylation by protein kinase A (PKA) on GABA(A)
      receptors (alpha1beta1gamma2L andalpha1beta3gamma2L) transiently expressed in HEK
      293T cells. Under conditions favorable for PKA activation, currents obtained
      using whole-cell patch clamp of lifted cells displayed increased rate and extent
      of the fast phases of desensitization, decreased rate of current deactivation
      after GABA removal, and prolongation of brief IPSC-like currents. Mutation of
      serine residues (beta1 S409, beta3 S407, beta3 S408) revealed that only beta1
      S409 and beta3 S408 were critical for the modulatory effect of PKA on GABA(A)
      receptor currents. Additionally, repeated pulse inhibition was increased in
      receptors after mutation of the critical serine to glutamate and decreased when
      the serine was mutated to alanine. These data demonstrate that PKA
      phosphorylation modulated GABA(A) receptor currents by increasing fast phases of
      macroscopic desensitization and suggest a role for PKA in regulating GABAergic
      IPSC duration.

PMID- 14684874
TI  - Stimulation in hippocampal region CA1 in behaving rats yields long-term
      potentiation when delivered to the peak of theta and long-term depression when
      delivered to the trough.
AB  - Experimental evidence suggests that the hippocampal theta rhythm plays a critical
      role in learning. Previous studies have shown long-term potentiation (LTP) to be
      preferentially induced with stimulation on the peak of local theta rhythm in
      region CA1 in anesthetized rats and with stimulation of the perforant path at the
      peak of theta in both anesthetized and behaving animals. We set out to determine
      the effects of tetanic burst stimulation in stratum radiatum of region CA1 in
      awake behaving animals, delivered during either the peak or the trough of the
      theta rhythm in the EEG. Bursts delivered to the peak resulted in an increase of
      17.9 +/- 0.94% in potential slope. When identical stimulation bursts were
      delivered to the trough of local theta waves, the potential slope decreased 12.9
      +/- 1.03%. This is the first report of LTP being preferentially induced at the
      peak of local theta rhythm in behaving animals in region CA1 and that LTD was
      found in response to tetanic stimulation at the trough of the local theta wave.
      The results are discussed within the framework of a recent theory that proposes
      that the theta rhythm sets the dynamics for alternating phases of encoding and
      retrieval (Hasselmo et al., 20021).

PMID- 14684873
TI  - Changes in GABA(A) receptor gene expression associated with selective alterations
      in receptor function and pharmacology after ethanol withdrawal.
AB  - Changes in the expression of subunits of the GABA type A (GABA(A)) receptor are
      implicated in the development of ethanol tolerance and dependence as well as in
      the central hyperexcitability associated with ethanol withdrawal. The impact of
      such changes on GABA(A) receptor function and pharmacological sensitivity was
      investigated with cultured rat hippocampal neurons exposed to ethanol for 5 d and
      then subjected to ethanol withdrawal. Both ethanol treatment and withdrawal were
      associated with a marked decrease in the maximal density of GABA-evoked Cl-
      currents, whereas the potency of GABA was unaffected. Ethanol exposure also
      reduced the modulatory efficacy of the benzodiazepine receptor agonists
      lorazepam, zolpidem, and zaleplon as well as that of the inverse agonists Ro 15
      4513 and FG 7142, effects that were associated with a reduced abundance of mRNAs
      encoding the receptor subunits alpha1, alpha3, gamma2L, and gamma2S. Ethanol
      withdrawal restored the efficacy of lorazepam, but not that of low concentrations
      of zolpidem or zaleplon, to control values. Flumazenil, which was ineffective in
      control neurons, and Ro 15-4513 each potentiated the GABA response after ethanol
      withdrawal. These effects of withdrawal were accompanied by upregulation of the
      alpha2, alpha3, and alpha4 subunit mRNAs as well as of the alpha4 protein.
      Diazepam or gamma-hydroxybutyrate, but not baclofen, prevented the changes in
      both GABA(A) receptor pharmacology and subunit mRNA levels induced by ethanol
      withdrawal. Changes in GABA(A) receptor gene expression induced by prolonged
      exposure to and withdrawal of ethanol are thus associated with altered GABA(A)
      receptor function and pharmacological sensitivity.

PMID- 14684876
TI  - Synchronous, focally modulated beta-band oscillations characterize local field
      potential activity in the striatum of awake behaving monkeys.
AB  - Synchronous oscillatory activity has been observed in a range of neural networks
      from invertebrate nervous systems to the human frontal cortex. In humans and
      other primates, sensorimotor regions of the neocortex exhibit synchronous
      oscillations in the beta-frequency band (approximately 15-30 Hz), and these are
      also prominent in the cerebellum, a brainstem sensorimotor region. However,
      recordings in the basal ganglia have suggested that such beta-band oscillations
      are not normally a primary feature of these structures. Instead, they become a
      dominant feature of neural activity in the basal ganglia in Parkinson's disease
      and in parkinsonian states induced by dopamine depletion in experimental animals.
      Here we demonstrate that when multiple electrodes are used to record local field
      potentials, 10-25 Hz oscillations can be readily detected in the striatum of
      normal macaque monkeys. These normally occurring oscillations are highly
      synchronous across large regions of the striatum. Furthermore, they are subject
      to dynamic modulation when monkeys perform a simple motor task to earn rewards.
      In the striatal region representing oculomotor activity, we found that small
      focal zones could pop in and out of synchrony as the monkeys made saccadic eye
      movements, suggesting that the broadly synchronous oscillatory activity
      interfaces with modular spatiotemporal patterns of task-related activity. We
      suggest that the background beta-band oscillations in the striatum could help to
      focus action-selection network functions of cortico-basal ganglia circuits.

PMID- 14684875
TI  - A novel secretory factor, Neurogenesin-1, provides neurogenic environmental cues
      for neural stem cells in the adult hippocampus.
AB  - Neurogenesis occurs in restricted regions in the adult mammalian brain, among
      which the neurogenesis in the hippocampal dentate gyrus plays the crucial role in
      learning and memory. To date, little is known about neurogenic cues, which result
      in the neuronal fate adoption of neural stem cells residing in neurogenic
      regions, especially neurogenic cues in adult hippocampal neurogenesis. In the
      present study, we show that hippocampal astrocytes and also dentate granule cells
      adjacent to neural stem cells secrete a newly cloned novel secretory factor,
      Neurogenesin-1. This protein contains three cysteine-rich domains and a unique
      sequence and contributes to neuronal differentiation of neural stem cells in the
      adult brain by preventing the adoption of a glial fate. Furthermore, the
      neurogenic activity detected in the hippocampal culture medium was markedly
      suppressed by the administration of an anti-Neurogenesin-1 antibody. These
      findings suggest endogenous mechanisms that induce adult hippocampal neurogenesis
      and propose an innovative treatment for the neurodegenerative diseases that cause
      loss of hippocampal neurons.

PMID- 14684877
TI  - fMRI of the conscious rabbit during unilateral classical eyeblink conditioning
      reveals bilateral cerebellar activation.
AB  - The relative contributions of the ipsilateral and contralateral cerebellar cortex
      and deep nuclei to delay eyeblink conditioning have been debated and are
      difficult to survey entirely using typical electrophysiological and lesion
      techniques. To address these issues, we used single-event functional magnetic
      resonance imaging (fMRI) in the conscious rabbit to visualize the entire
      cerebellum simultaneously during eyeblink conditioning sessions. Examination of
      the blood oxygenation level-dependent (BOLD) response to a visual conditioning
      stimulus early in training revealed significant bilateral learning-related
      increases in the BOLD response in the anterior interpositus nucleus (IPA) and
      significant bilateral deactivation in hemispheric lobule VI (HVI) of the
      cerebellar cortex. Later in training, the BOLD response remained bilateral in the
      cortex and predominantly ipsilateral in the IPA. Conditioning stimulus-alone
      trials after conditioning revealed that both sides of HVI were affected similarly
      but that only the ipsilateral interpositus nucleus was activated. These results
      suggest that both sides of HVI normally influence the side of the IPA being
      conditioned and illustrate how fMRI can be used to examine multiple brain regions
      simultaneously in an awake, behaving animal to discover more rapidly the neural
      substrates of learning and memory.

PMID- 14684878
TI  - Activity-dependent redistribution and essential role of cortactin in dendritic
      spine morphogenesis.
AB  - The number and shape of dendritic spines are influenced by activity and regulated
      by molecules that organize the actin cytoskeleton of spines. Cortactin is an F
      actin binding protein and activator of the Arp2/3 actin nucleation machinery that
      also interacts with the postsynaptic density (PSD) protein Shank. Cortactin is
      concentrated in dendritic spines of cultured hippocampal neurons, and the N
      terminal half of the protein containing the Arp2/3 and F-actin binding domains is
      necessary and sufficient for spine targeting. Knockdown of cortactin protein by
      short-interfering RNA (siRNA) results in depletion of dendritic spines in
      hippocampal neurons, whereas overexpression of cortactin causes elongation of
      spines. In response to synaptic stimulation and NMDA receptor activation,
      cortactin redistributes rapidly from spines to dendritic shaft, correlating with
      remodeling of the actin cytoskeleton, implicating cortactin in the activity
      dependent regulation of spine morphogenesis.

PMID- 14684879
TI  - Neurotrophins elevate cAMP to reach a threshold required to overcome inhibition
      by MAG through extracellular signal-regulated kinase-dependent inhibition of
      phosphodiesterase.
AB  - Inhibitors of regeneration in myelin, such as myelin-associated glycoprotein
      (MAG), play an important role in preventing regeneration after CNS injury.
      Elevation of cAMP, either with dibutyryl-cAMP (db-cAMP) or by priming with a
      variety of neurotrophins, overcomes inhibition by MAG and myelin. However,
      activation of cAMP is not generally regarded as a signaling pathway for
      neurotrophins. Here we show that the NGF-like neurotrophins overcome inhibition
      by MAG by activating tyrosine kinase receptors. We also show that activation of
      extracellular signal-regulated kinase (Erk) by BDNF is required to overcome
      inhibition by MAG, and that activated Erk transiently inhibits phosphodiesterase
      4 (PDE4), the enzyme that hydrolyzes cAMP. Inhibition of PDE4 then allows cAMP to
      increase and so initiates the pathway to overcome inhibition. Furthermore, we
      also show that basal levels of Erk activation and basal cAMP levels contribute to
      the effects of db-cAMP by pushing the combined levels of cAMP above a threshold
      required to overcome inhibition. Together, these results not only show how NGF
      like neurotrophins can elevate cAMP and overcome inhibition but also point to a
      novel mechanism of cross talk in neurons from the Erk to the cAMP signaling
      pathways.

PMID- 14684880
TI  - European survey on Campylobacter surveillance and diagnosis 2001.
AB  - Two surveys have been conducted on behalf of the Campylobacter Working Group with
      the aim of assessing the feasibility of a European network on human Campylobacter
      infections. The first survey, conducted in 18 countries, collected information
      about diagnostic methods used for surveillance purpose while the second one,
      conducted among 10 European countries, gathered data on diagnostic methods and
      procedures in primary laboratories. Seventeen of the 18 countries had a
      surveillance system for Campylobacter infections and 13 a national reference
      laboratory. The case definition used for the surveillance in all these countries
      included laboratory confirmation. No commonly applicable subtyping methods were
      applied. Concerning primary laboratories dealing with Campylobacter infections,
      only a few of them reported directly to the national level, and antimicrobial
      susceptibility testing was performed by about half of the laboratories. These
      surveys indicated that a basic infrastructure for a wide European Campylobacter
      surveillance exists.

PMID- 14684881
TI  - Surveillance of human Campylobacter infections in France--part 1--which data? A
      study of microbiological laboratories, 2000.
AB  - The frequency of Campylobacter infections in humans, their potential severity,
      and the existence of preventive measures justify the implementation of a
      surveillance system for these infections. Before the implementation of the
      surveillance system, a survey of the Campylobacter diagnostic practices in the
      laboratories was performed. In the laboratories that responded, most investigated
      for Campylobacter at least once in 1999. Identification of the Campylobacter
      species was carried out by 86% of hospital laboratories and 37% of private
      laboratories. Antibiotic sensitivity tests were carried out by 75% and 32% of
      them respectively. Many laboratories test for Campylobacter in stool samples
      using comparable methods showing the feasibility of a surveillance system.

PMID- 14684882
TI  - Surveillance of human Campylobacter infections in France--part 2--implementation
      of national surveillance.
AB  - In 2001, one year after the study of microbiological laboratories that showed the
      feasibility of a surveillance of Campylobacter infections, 1389 private
      laboratories were asked whether they would be willing to participate. The high
      proportion of positive responses (48%, 661) allowed the implementation on 1 April
      2002 of surveillance of human Campylobacter infections.

PMID- 14684883
TI  - The 11th international workshop on Campylobacter, Helicobacter and related
      Organisms (CHRO), 2001.
AB  - Over 700 participants from 54 countries attended the eleventh Campylobacter,
      Helicobacter and Related Organisms (CHRO) meeting in September 2001. This meeting
      was an opportunity to update and better understand the microbiological and
      epidemiological complexities of Campylobacter. The mechanism of pathogenesis of
      this bacteria is not yet fully understood and important progress was made in the
      microbiological characterisation. The availability of over 100 different strain
      characteristics from various locations all over Europe, brought together by
      Campynet, is an invaluable tool for achieving this aim. There is increasing
      evidence to suggest that different risk factors exist for different species of
      Campylobacter. The link between antibiotic use in farm animals and increased
      resistance to some antimicrobials for humans still needs to be proved and some
      contradictory results reported on this issue.

PMID- 14684885
TI  - First look at RNA in L-configuration.
AB  - Nucleic acid molecules in the mirror image or L-configuration are unknown in
      nature and are extraordinarily resistant to biological degradation. The
      identification of functional L-oligonucleotides called Spiegelmers offers a novel
      approach for drug discovery based on RNA. The sequence r(CUGGGCGG).r(CCGCCUGG)
      was chosen as a model system for structural analysis of helices in the L
      configuration as the structure of the D-form of this sequence has previously been
      determined in structural studies of 5S RNA domains, in particular domain E of the
      Thermus flavus 5S rRNA [Perbandt et al. (2001), Acta Cryst. D57, 219-224].
      Unexpectedly, the results of crystallization trials showed little similarity
      between the D- and the L-forms of the duplex in either the crystallization hits
      or the diffraction performance. The crystal structure of this L-RNA duplex has
      been determined at 1.9 A resolution with R(work) and R(free) of 23.8 and 28.6%,
      respectively. The crystals belong to space group R32, with unit-cell parameters a
      = 45.7, c = 264.6 A. Although there are two molecules in the asymmetric unit
      rather than one, the structure of the L-form arranges helical pairs in a head-to
      tail fashion to form pseudo-continuous infinite helices in the crystal as in the
      D-form. On the other hand, the wobble-like G.C(+) base pair seen in the D-RNA
      analogue does not appear in the L-RNA duplex, which forms a regular double
      helical structure with typical Watson-Crick base pairing.

PMID- 14684884
TI  - Clonal circulation of Salmonella enterica serotype Heidelberg in Italy?
AB  - Phenotypic and genetic characteristics of 21 strains of Salmonella serotype
      Heidelberg isolated in the years 1999-2003 from different sources in Italy were
      studied. Susceptibility patterns, plasmid analysis, and PFGE were used as
      epidemiological markers. Although non-homogeneous drug resistance patterns and
      plasmid profiles had been detected, PFGE patterns suggest the hypothesis of a
      nationwide clonal spread of this serotype associated with poultry.

PMID- 14684886
TI  - Structure of the dodecamer r(GAUCACUUCGGU) with four 5'-overhang nucleotides.
AB  - The crystal structure of an RNA dodecamer, r(GAUCACUUCGGU), was solved at 2.6 A
      resolution by the molecular-replacement method and refined to an R(work) of 18.8%
      (R(free) = 22.8%) using 2494 reflections. The dodecamer crystallized in the
      monoclinic space group C2, with unit-cell parameters a = 71.34, b = 39.98, c =
      32.47 A, beta = 104.7 degrees and two independent strands in the asymmetric unit.
      The dodecamer adopts an octamer duplex structure with four 5'-overhang residues
      (G1A2U3C4), which form Watson-Crick base pairs with another four 5'-overhang
      residues of a symmetry-related duplex. The octamer duplex (ACUUCGGU) contains at
      its center four mismatched base pairs flanked by two Watson-Crick base pairs. The
      mismatched bases form two G.U wobble base pairs at the ends and two U.C base
      pairs at the center, with one base-base hydrogen bond N4(C).O4(U) and a water
      bridge connecting the N(3) of the cytosine and uridine. The present study
      reinforces the concept of the stability of the conformation of UUCG in RNA double
      helical structures.

PMID- 14684887
TI  - Substrate recognition and selectivity of plant glycerol-3-phosphate
      acyltransferases (GPATs) from Cucurbita moscata and Spinacea oleracea.
AB  - Stromal glycerol-3-phosphate acyltransferases (GPAT) are responsible for the
      selective incorporation of saturated and unsaturated fatty-acyl chains into
      chloroplast membranes, which is an important determinant of a plant's ability to
      tolerate chilling temperatures. The molecular mechanisms of plant chilling
      tolerance were elucidated by creating chimeric GPATs between squash (Cucurbita
      moscata, chilling-sensitive) and spinach (Spinacea oleracea, chilling-tolerant)
      and the results were interpreted using structural information on squash GPAT
      determined by X-ray crystallography at 1.55 A resolution. Enzymatic analysis of
      the chimeric GPATs showed that the chimeric GPATs containing the spinach region
      from residues 128 to 187 prefer the 18:1 unsaturated fatty acid rather than 16:0
      saturated fatty acid. Structure analysis suggests that the size and character of
      the cavity that is formed from this region determines the specific recognition of
      acyl chains.

PMID- 14684888
TI  - The application of multivariate statistical techniques improves single-wavelength
      anomalous diffraction phasing.
AB  - Recently, there has been a resurgence in phasing using the single-wavelength
      anomalous diffraction (SAD) experiment; data from a single wavelength in
      combination with techniques such as density modification have been used to solve
      macromolecular structures, even with a very small anomalous signal. Here, a
      formulation for SAD phasing and refinement employing multivariate statistical
      techniques is presented. The equation developed accounts explicitly for the
      correlations among the observed and calculated Friedel mates in a SAD experiment.
      The correlated SAD equation has been implemented and test cases performed on real
      diffraction data have revealed better results compared with currently used
      programs in terms of correlation with the final map and obtaining more reliable
      phase probability statistics.

PMID- 14684889
TI  - On the routine use of soft X-rays in macromolecular crystallography. Part II.
      Data-collection wavelength and scaling models.
AB  - Complete and highly redundant data sets were collected at nine different
      wavelengths between 0.80 and 2.65 A on a xenon derivative of porcine pancreatic
      elastase in both air and helium atmospheres. The magnitude of the anomalous
      signal, as assessed by the xenon-peak height in the anomalous difference
      Patterson synthesis, is affected by the wavelength of data collection as well as
      by the scaling model used. For data collected at wavelengths longer than 1.7 A,
      the use of a three-dimensional scaling protocol is essential in order to obtain
      the highest possible anomalous signal. Based on the scaling protocols currently
      available, the optimal wavelength range for data collection appears to be between
      2.1 and 2.4 A. Beyond that, any further increase in signal will be compensated
      for or even superseded by a concomitant increase in noise, which cannot be fully
      corrected for. Data collection in a helium atmosphere yields higher I/sigma(I)
      values, but not significantly better anomalous differences, than data collection
      in air.

PMID- 14684890
TI  - Flash-cooling of macromolecular crystals in a capillary to overcome increased
      mosaicity.
AB  - This paper describes the usefulness of flash-cooling in a capillary (FCC) for X
      ray diffraction data collection from macromolecular crystals. FCC may be applied
      when conventional cooling using a cryoloop fails. This technique cools crystals
      in a capillary instead of in a cryoloop and thus cools crystals more slowly than
      conventional cooling. Measurements of cooling rates have shown that the time
      taken to reach the final temperature is two to eight times longer using FCC than
      using a cryoloop, depending on the volume of cryoprotectant solution around the
      crystal. Using this cooling technique, the crystal structures of isocitrate
      dehydrogenase and protein L-isoaspartate O-methyltransferase have been solved at
      1.95 and at 2.50 A resolution, respectively. Both crystals could not be cooled by
      the conventional method using a cryoloop. Moreover, diffraction data from
      crystals of the hypothetical proteins PH-A and PH-B were also collected
      successfully using the FCC method. These results show that some crystals,
      especially larger ones, need to be cooled slowly.

PMID- 14684891
TI  - Structure of the snake-venom toxin convulxin.
AB  - Snake venoms contain a number of proteins that interact with components of the
      haemostatic system that promote or inhibit events leading to blood-clot
      formation. The snake-venom protein convulxin (Cvx) binds glycoprotein (GP) VI,
      the platelet receptor for collagen, and triggers signal transduction. Here, the
      2.7 A resolution crystal structure of Cvx is presented. In common with other
      members of this snake-venom protein family, Cvx is an alphabeta-heterodimer and
      conforms to the C-type lectin-fold topology. Comparison with other family members
      allows a set of Cvx residues that form a concave surface to be putatively
      implicated in GPVI binding. Unlike other family members, with the exception of
      flavocetin-A (FL-A), Cvx forms an (alphabeta)(4) tetramer. This oligomeric
      structure is consistent with Cvx clustering GPVI molecules on the surface of
      platelets and as a result promoting signal transduction activity. The Cvx
      structure and the location of the putative binding sites suggest a model for this
      multimeric signalling assembly.

PMID- 14684892
TI  - Refinement of the structure of human Rab5a GTPase domain at 1.05 A resolution.
AB  - Rab5 is a GTPase that regulates early endosome fusion. Its GTPase domain crystal
      structure is reported here at 1.05 A resolution in complex with a GTP-analog
      molecule. It provides the highest resolution three-dimensional model so far
      obtained for proteins from the Ras-like GTPase family. This study allows
      extension of structural examination of the GTPase machinery as well as of high
      resolution protein structures in general. For example, a buried water-molecule
      network was observed underneath the switch regions, which is consistent with the
      functional roles of these regions in the molecular-switching process.
      Furthermore, residues of multiple conformation and clustered distribution of
      anisotropic thermal motions of the protein molecule may have general implications
      for the function of Ras-like GTPases.

PMID- 14684893
TI  - Structures of d(Gm5)CGm5CGCGC) and d(GCGCGm5CGm5C): effects of methylation on
      alternating DNA octamers.
AB  - The crystal structures of two alternating octamers d(Gm(5)CGm(5)CGCGC) and
      d(GCGCGm(5)CGm(5)C) have been determined at 1.7 and 1.9 A resolution with
      R(work)/R(free) of 16.9/19.6% and 17.9/19.8%, respectively. The two octamers
      crystallized in the same tetragonal space group P4(3)2(1)2, with unit-cell
      parameters a = b = 43.0, c = 24.9 A and a = b = 43.1, c = 24.7 A, respectively.
      Both structures adopt the A-type double helix and the abutting crystal packing.
      Despite the different positions of the methylated cytosine in the sequence, the
      two octamers display essentially the same conformation. The close similarity of
      the two structures indicates that methylation at different positions in a DNA
      sequence does not affect the helical conformation of the alternating DNA octamer.
      Investigation of other related crystal structures implies that methylation of
      cytosine stabilizes the A-type conformation for alternating DNA sequences
      beginning with a 5'-purine but is beneficial to the Z-type conformation for
      alternating DNA sequences beginning with a 5'-pyrimidine.

PMID- 14684894
TI  - Structure of an acidic phospholipase A2 from Indian saw-scaled viper (Echis
      carinatus) at 2.6 A resolution reveals a novel intermolecular interaction.
AB  - The crystal structure of an acidic phospholipase A(2) from the venom of Echis
      carinatus (saw-scaled viper; scPLA(2)) has been determined at 2.6 A resolution
      and refined to a crystallographic R factor of 0.192. Although the overall
      structure of scPLA(2) is essentially similar to those of other group II acidic
      PLA(2)s from different species, it shows unique features in several parts.
      Particularly noteworthy is the C-terminal part, which folds differently to those
      of other group II PLA(2)s. This part is considered to be responsible for
      inhibition of the platelet-aggregation activity. The calcium-binding loop is
      tightly organized with sevenfold coordination. Another striking feature of
      scPLA(2) is the involvement of Asn79 O(delta1) of a symmetry-related molecule in
      a coordination linkage with Ca(2+) of the calcium-binding loop. This is the first
      observation of an internal metal ion participating in an intermolecular
      interaction. The beta-wing of a molecule is deeply inserted into the hydrophobic
      channel of another molecule and forms several intermolecular interactions. This
      results in the formation of an infinite chain of molecules. These chains are
      stacked in an antiparallel arrangement in the crystals.

PMID- 14684895
TI  - Phasing via SAD/MAD data: the method of the joint probability distribution
      functions.
AB  - The method of the joint probability distribution functions is applied to derive a
      probabilistic formula which is able to phase reflections in the MAD case
      accurately, under the condition that the anomalous-scatterer substructure has
      been defined previously. The mathematical approach takes into account both
      measurement and model errors, which are treated as primitive random variables, as
      well as the atomic positions defining the unknown part of the crystal structure.
      The probabilistic formula has the classical tangent expression. All the
      parameters influencing the phase estimation are immediately interpretable in
      terms of experimental quantities: i.e. anomalous and dispersive differences,
      magnitude of the errors and normalized structure-factor moduli. The formula has
      been applied to several practical cases: a procedure has also been designed which
      is able to refine the phases and lead to easily interpretable electron-density
      maps.

PMID- 14684896
TI  - Structure of thaumatin in a hexagonal space group: comparison of packing contacts
      in four crystal lattices.
AB  - The intensely sweet protein thaumatin has been crystallized in a hexagonal
      lattice after a temperature shift from 293 to 277 K. The structure of the protein
      in the new crystal was solved at 1.6 A resolution. The protein fold is identical
      to that found in three other crystal forms grown in the presence of crystallizing
      agents of differing chemical natures. The proportions of lattice interactions
      involving hydrogen bonds, hydrophobic or ionic groups differ greatly from one
      form to another. Moreover, the distribution of acidic and basic residues taking
      part in contacts also varies. The hexagonal packing is characterized by the
      presence of channels parallel to the c axis that are so wide that protein
      molecules can diffuse through them.

PMID- 14684897
TI  - Structure of d(GCGAAAGC) (hexagonal form): a base-intercalated duplex as a stable
      structure.
AB  - A DNA fragment d(GCGAAAGC), postulated to adopt a stable mini-hairpin structure
      on the basis of its extraordinary properties, has been X-ray analyzed. Two
      octamers related by a crystallographic twofold symmetry are aligned in an
      antiparallel fashion and associate to form a duplex, which is maintained by two
      Watson-Crick G.C base pairs and a subsequent sheared G.A pair at both ends. The
      central two A residues are free from base-pair formation. The corresponding base
      moieties of the two strands are intercalated and stacked on each other, forming a
      long column of G(1)-C(2)-G(3)-A(4)-A(5)(*)-A(5)-A(4)(*)-G(3)(*)-C(2)(*)-G(1)(*)
      (asterisks indicate the counter-strand). The Watson-Crick and major-groove sites
      of the four stacked adenine bases are exposed to the solvent region, suggesting a
      functional role. Since this structural motif is similar to those found in the
      nonamers d(G(Br)CGAAAGCT) and d(G(I)CGAAAGCT), the base-intercalated duplex may
      be a stable form of the specific sequence. Electrophoresis results suggest that
      the octamer has two states, monomeric and dimeric, in solution depending on the
      Mg(2+) concentration. The present duplex is preferred under the crystallization
      conditions, which correspond to physiologically allowed conditions.

PMID- 14684898
TI  - Structure and implications for the thermal stability of phosphopantetheine
      adenylyltransferase from Thermus thermophilus.
AB  - Phosphopantetheine adenylyltransferase (PPAT) is an essential enzyme in bacteria
      that catalyzes the rate-limiting step in coenzyme A (CoA) biosynthesis by
      transferring an adenylyl group from ATP to 4'-phosphopantetheine (Ppant),
      yielding 3'-dephospho-CoA (dPCoA). The crystal structure of PPAT from Thermus
      thermophilus HB8 (Tt PPAT) complexed with Ppant has been determined by the
      molecular-replacement method at 1.5 A resolution. The overall fold of the enzyme
      is almost the same as that of Escherichia coli PPAT, a hexamer having point group
      32. The asymmetric unit of Tt PPAT contains a monomer and the crystallographic
      triad and dyad coincide with the threefold and twofold axes of the hexamer,
      respectively. Most of the important atoms surrounding the active site in E. coli
      PPAT are conserved in Tt PPAT, indicating similarities in their substrate binding
      and enzymatic reaction. The notable difference between E. coli PPAT and Tt PPAT
      is the simultaneous substrate recognition by all six subunits of Tt PPAT compared
      with substrate recognition by only three subunits in E. coli PPAT. Comparative
      analysis also revealed that the higher stability of Tt PPAT arises from
      stabilization of each subunit by hydrophobic effects, hydrogen bonds and entropic
      effects.

PMID- 14684899
TI  - Crystallization of the effector-binding domains of BenM and CatM, LysR-type
      transcriptional regulators from Acinetobacter sp. ADP1.
AB  - BenM, a member of the LysR-type family of transcriptional regulators, controls
      genes for benzoate degradation in the Gram-negative bacterium Acinetobacter sp.
      strain ADP1. Recent studies show that BenM activates benABCDE expression
      synergistically in response to two effector ligands: cis,cis-muconate (CCM) and
      benzoate. As an initial step in investigating the structural basis of dual
      effector response, the effector-binding domain of BenM (BenM-EBD) was
      crystallized by the microbatch-under-oil technique with conditions optimized from
      high-throughput screens performed by the Hauptman-Woodward Institute. Data
      collection quality crystals of BenM-EBD belonged to space group P2(1)2(1)2(1),
      diffracted to 2.3 A and had unit-cell parameters a = 65.64, b = 66.34, c = 117.46
      A. The influence of effector ligands on crystal formation was also evaluated. The
      presence of benzoate or CCM impaired the formation of crystals. The presence of
      both effectors together resulted in a dramatic decrease in the production of
      crystals. The effector-binding domain of CatM, a homolog of BenM, was also
      crystallized.

PMID- 14684900
TI  - Cloning, expression, purification, crystallization and preliminary diffraction
      analysis of the C-terminal catalytic domain of human poly(ADP-ribose) polymerase.
AB  - Two fragments of the C-terminal catalytic domain of human poly(ADP-ribose)
      polymerase (catPARP), Met-catPARP and Gly-Ser-catPARP, were purified and
      crystallized. Both catPARP crystals belong to space group C2, with almost the
      same unit-cell parameters. However, the shapes and harvest periods of both
      crystals were quite different owing to the slight mutation at the N-terminal
      position. Gly-Ser-catPARP was found to be more suitable for X-ray crystallography
      and crystals showed diffraction to at least 3.5 A resolution.

PMID- 14684901
TI  - Preliminary crystallographic analysis of the NAC domain of ANAC, a member of the
      plant-specific NAC transcription factor family.
AB  - The NAC domain (residues 1-168) of ANAC, encoded by the abscisic acid-responsive
      NAC gene from Arabidopsis thaliana, was recombinantly produced in Escherichia
      coli and crystallized in hanging drops. Three morphologically different crystal
      forms were obtained within a relatively narrow range of conditions: 10-15% PEG
      4000 and 0.1 M imidazole/malic acid buffer pH 7.0 in the reservoir, 3.2-7.7 mg
      ml(-1) protein stock and a 1:1 ratio of reservoir to protein solution in the
      hanging drop. One of the crystal forms, designated crystal form III, was found to
      be suitable for further X-ray analysis. Form III crystals belong to space group
      P2(1)2(1)2(1), with unit-cell parameters a = 62.0, b = 75.2, c = 80.8 A at 100 K.
      The unit-cell volume is consistent with two molecules in the asymmetric unit and
      a peak in the native Patterson map suggests the presence of a non
      crystallographic twofold axis parallel to a crystallographic axis. Size-exclusion
      chromatography of the NAC domain showed that the dimeric state is also the
      preferred state in solution and probably represents the biologically active form.
      Data sets were collected from four potential heavy-atom derivatives of the form
      III crystals. The derivatized crystals are reasonably isomorphous with the non
      derivatized crystals and the four data sets are being evaluated for use in
      structure determination by multiple isomorphous replacement.

PMID- 14684902
TI  - Crystallization and preliminary X-ray analysis of 5'-methylthioribose kinase from
      Bacillus subtilis and Arabidopsis thaliana.
AB  - Recombinant Bacillus subtilis 5'-methylthioribose (MTR) kinase has been
      expressed, purified and subsequently crystallized using the hanging-drop vapor
      diffusion technique. With PEG 2000MME as the precipitant, two different crystal
      forms have been grown in the absence and presence of the detergent CHAPS. These
      crystals belong to space groups P2(1)2(1)2(1) (unit-cell parameters a = 193.7, b
      = 83.2, c = 51.6 A) and P2(1)2(1)2 (unit-cell parameters a = 213.8, b = 83.2, c =
      51.5 A), respectively. The crystals grown in the presence of CHAPS diffract to
      2.2 A resolution at Station X8C, National Synchrotron Light Source (NSLS). For
      both crystal forms, the presence of two monomers per asymmetric unit is predicted
      (Matthews coefficient V(M) = 2.29 and 2.52 A(3) Da(-1), respectively).
      Recombinant C-terminally histidine-tagged Arabidopsis thaliana MTR kinase has
      also been expressed, purified and refolded into its active form. Rod-shaped
      crystals of this protein were grown from PEG 8000 using the hanging-drop vapor
      diffusion technique. These crystals exhibit the symmetry of space group C2 (unit
      cell parameters a = 162.3, b = 83.3, c = 91.0 A, beta = 117.8 degrees ) and
      diffract to 1.9 A resolution at Station X8C, NSLS. Two monomers are estimated to
      be present in the asymmetric unit (V(M) = 2.82 A(3) Da(-1)).

PMID- 14684903
TI  - Crystallization and preliminary crystallographic analysis of beta-hydroxyacyl ACP
      dehydratase (FabZ) from Plasmodium falciparum.
AB  - The malarial parasite Plasmodium falciparum synthesizes fatty acids by the type
      II mechanism. In this cycle, the dehydration of the beta-hydroxyacyl acyl carrier
      protein is catalyzed by FabZ. Purified FabZ has been crystallized using the
      hanging-drop vapour-diffusion and microbatch techniques. The crystals are
      orthorhombic, with space group I222 or I2(1)2(1)2(1) and unit-cell parameters a =
      71.78, b = 81.99, c = 97.49 A. A complete data set to a resolution of 2.5 A has
      been collected under cryoconditions (100 K) using a MAR imaging-plate detector
      system mounted on a rotating-anode X-ray generator.

PMID- 14684904
TI  - Purification, crystallization and preliminary X-ray diffraction data of L7Ae sRNP
      core protein from Pyrococcus abyssii.
AB  - The L7Ae sRNP core protein from Pyrococcus abyssii was crystallized using the
      sitting-drop vapour-diffusion method. Crystals were obtained in the presence of
      MgCl(2), PEG 2000 MME and acetate buffer at pH 4.0. A native data set has been
      collected at 2.9 A resolution using a rotating-anode generator at room
      temperature. Crystals belong to the orthorhombic space group P2(1)2(1)2, with
      unit-cell parameters a = 70.7, b = 112.9, c = 34.8 A. There are two monomers of
      MW 14 200 Da per asymmetric unit and the packing density V(M) is 2.45 A(3) Da(
      1). A molecular-replacement analysis gave solutions for the rotation and
      translation functions.

PMID- 14684905
TI  - Crystallization and preliminary X-ray diffraction study of the class A beta
      lactamase SED-1 and its mutant SED-G238C from Citrobacter sedlakii.
AB  - SED-1, a class A beta-lactamase from Citrobacter sedlakii, is a CTX-M-type
      extended-spectrum beta-lactamase that has the ability to hydrolyze expanded
      spectrum cephalosporins such as cefotaxime. SED-1 and a SED mutant in which
      Gly238 has been replaced by a cysteine, forming a disulfide bridge with the other
      Cys residue located at position 69 (SED-G238C), have been crystallized. The
      crystals belong to the monoclinic space group C2, with unit-cell parameters a =
      188.09, b = 73.65, c = 105.41 A, beta = 121.67 degrees for SED-1 and a = 187.64,
      b = 73.2, c = 103.89 A, beta = 121.89 degrees for the SED-G238C mutant. X-ray
      diffraction data were collected to maximum resolutions of 2.4 A for SED-1 and 2.0
      A for SED-G238C.

PMID- 14684906
TI  - Crystallization and preliminary X-ray crystallographic analysis of the N-terminal
      domain of XpsE protein from Xanthomonas campestris, an essential component of the
      type II protein-secretion machinery.
AB  - Secretion of pre-folded extracellular proteins across the outer membrane of Gram
      negative bacteria is mainly assisted by the type II secretion machinery composed
      of 12-15 proteins. Here, the crystallization and preliminary analysis of one of
      the essential components of Xanthomonas campestris secretion machinery, the 21
      kDa N-terminal domain of XpsE protein (XpsE(N)), are reported. XpsE(N) has been
      crystallized at 277 K using PEG 400 as precipitant. These crystals belong to the
      tetragonal space group P4(1)2(1)2 (or P4(3)2(1)2), with unit-cell parameters a =
      b = 56.1, c = 102.7 A. A 98.5% complete native data set from a frozen crystal has
      been collected to 2.0 A resolution at 100 K with an overall R(merge) of 5.0%. The
      presence of one subunit of XpsE(N) per asymmetric unit gives a crystal volume per
      protein weight (V(M)) of 1.92 A(3) Da(-1) and a solvent content of 36.1%.

PMID- 14684907
TI  - Crystallization and preliminary X-ray analysis of tryptophan synthase alpha
      subunits from Escherichia coli.
AB  - Tryptophan synthase alpha-subunit (alphaTS) catalyzes the cleavage of indole-3
      glycerolphosphate to glyceraldehyde-3-phosphate and indole, which is channelled
      to the active site of the associated beta-subunit (betaTS), where it reacts with
      serine to yield the amino acid tryptophan in tryptophan biosynthesis. The alphaTS
      from Escherichia coli is a 268 amino-acid protein with no disulfide bonds or
      prosthetic groups. Although the crystallization of the subunits from E. coli has
      been attempted over many years, there have been no reports of an X-ray structure.
      To explore the molecular origin of the conformational stabilization mechanism of
      alphaTS, the alpha-subunit protein was overexpressed in E. coli and crystallized
      using the hanging-drop vapour-diffusion method at 298 K. A native data set to 2.8
      A resolution was obtained from a flash-cooled crystal upon exposure to Cu Kalpha
      X-rays. The crystal belongs to the monoclinic space group C2, with unit-cell
      parameters a = 162.27, b = 44.48, c = 71.52 A, beta = 106.56 degrees. The
      asymmetric unit contains two molecules of alphaTS, giving a crystal volume per
      protein mass (V(M)) of 2.16 A(3) Da(-1) and a solvent content of 43.18%.

PMID- 14684908
TI  - Expression, purification, crystallization and preliminary crystallographic
      analysis of the diarrhoea-causing and virulence-determining region of rotaviral
      nonstructural protein NSP4.
AB  - The region spanning the tetrameric coiled-coil domain and the interspecies
      variable virulence-determining region of the cytoplasmic tail of rotaviral
      nonstructural protein NSP4 has been crystallized. The crystals belong to space
      group I222, with unit-cell parameters a = 30.70, b = 38.07, c = 181.62 A, and
      contain two molecules in the asymmetric unit. Diffraction data have been
      collected utilizing a MAR imaging plate to a resolution of 2.2 A. The tetramer is
      generated by the crystallographic dyad along the c axis.

PMID- 14684909
TI  - Co-crystallization of Leptospira interrogans peptide deformylase with a potent
      inhibitor and molecular-replacement schemes with eight subunits in an asymmetric
      unit.
AB  - Translation initiation in eubacteria involves a formylmethionine at the N
      terminus of newly synthesized polypeptides. This N-formyl group is removed by
      peptide deformylase (PDF) during the post-translation process. Such a
      formylation/deformylation cycle is essential for the cell survival of eubacteria,
      but is not utilized in eukaryotic cytosolic protein biosynthesis. In view of the
      absence of deformylase activity in mammalian cells, this is an attractive target
      for the design of novel antibiotic drugs. Co-crystallization of peptide
      deformylase from Leptospira interrogans (LiPDF) with its natural inhibitor
      actinonin produced diffraction-quality crystals that belong to space group P2(1),
      with unit-cell parameters a = 87.5, b = 119.1, c = 95.8 A, beta = 111.6 degrees.
      The 3.1 A resolution data set collected in-house was used to obtain phases by
      molecular replacement. Three schemes for the correction of the preliminary
      solutions were proposed and proved successful in determining the structure of
      LiPDF with eight subunits in the asymmetric unit.

PMID- 14684910
TI  - Crystallization of the crenarchaeal SRP core.
AB  - Protein translocation across or targeting to membranes mediated by the signal
      recognition particle (SRP) is a universal mechanism conserved in all domains of
      life. SRP54 from the crenarchaeon Sulfolobus solfataricus has been recombinantly
      expressed and crystallized with and without SRP RNA helix 8. The RNA has been
      transcribed in vitro using ribozyme technology. Both crystal forms are perfect
      merohedral twins. While SRP54 alone is hemihedrally twinned, the crystals of the
      SRP54-helix 8 complex indicate tetartohedral twinning, which has not previously
      been observed in protein crystals. The tetartohedral twinning is enabled by a
      special diamond-like packing in a trigonal crystal.

PMID- 14684911
TI  - Crystallization and preliminary X-ray diffraction studies of DNA decamer
      d(CCAGGCCTGG) complexed with cobalt(III)-pepleomycin.
AB  - Crystals of the self-complementary oligonucleotide d(CCAGGCCTGG) [Heinemann &
      Alings (1989), J. Mol. Biol. 210, 369-381] complexed with the hydroperoxide of
      cobalt-pepleomycin (CoPEP) were obtained by the hanging-drop vapour-diffusion
      method at 298 K. An X-ray diffraction data set was collected to 2.8 A at 100 K.
      The crystal belonged to space group P2(1)2(1)2(1), with unit-cell parameters a =
      34.52, b = 59.88, c = 72.93 A.

PMID- 14684912
TI  - Crystallization and preliminary X-ray diffraction studies of the quorum-sensing
      regulator TraM from Agrobacterium tumefaciens.
AB  - TraM is a 11.4 kDa protein involved in the control of the conjugal transfer of
      Agrobacterium tumefaciens Ti plasmids by quorum-sensing. TraM was overexpressed
      and purified from Escherichia coli. This protein binds to the transcriptional
      regulator TraR, abolishing its function. Size-exclusion chromatography and
      dynamic light scattering show that the recombinant protein has an apparent
      molecular weight of 30 kDa in solution. Crystals have been obtained of both
      native and selenomethionine-substituted TraM by the vapour-diffusion method.
      Crystals diffract to 1.67 A and belong to the space group P2(1)2(1)2, with unit
      cell parameters a = 76.43, b = 47.09, c = 47.46 A and two molecules in the
      asymmetric unit. A two-wavelength MAD data set for the selenomethionine
      substituted form has been collected to a resolution of 2.0 A. The selenium
      substructure (five out of six possible sites) has been solved using direct
      methods.

PMID- 14684913
TI  - A unique dye-decolorizing peroxidase, DyP, from Thanatephorus cucumeris Dec 1:
      heterologous expression, crystallization and preliminary X-ray analysis.
AB  - The dye-decolorizing peroxidase DyP is a key enzyme in the decolorizing fungus
      Thanatephorus cucumeris Dec 1 that degrades azo and antraquinone dyes. The gene
      dyp from T. cucumeris Dec 1, which has low homology to other peroxidase genes,
      was cloned and transformed into Aspergillus oryzae and glycosylated DyP was
      expressed at high levels. Purified DyP was deglycosylated using GST Endo F1 and
      then crystallized in a strong magnetic field (10 T) at 283 K using ammonium
      sulfate as precipitant. X-ray diffraction data to 2.96 A resolution collected
      from a native crystal at the Photon Factory (Tsukuba, Japan) showed that the
      crystal belonged to the hexagonal space group P6(5)22, with unit-cell parameters
      a = b = 136.15, c = 363.46 A. The asymmetric unit of the crystal contained four
      DyP molecules, with a corresponding Matthews coefficient (V(M)) of 2.50 A(3) Da(
      1) and a solvent content of 51%. Heavy-atom derivatives of DyP have been obtained
      and electron-density maps have been calculated. The haem is visible and
      continuous electron density between the haem and protein clearly indicates the
      location of the proximal histidine ligand.

PMID- 14684914
TI  - Crystallization of Arabidopsis thaliana acetohydroxyacid synthase in complex with
      the sulfonylurea herbicide chlorimuron ethyl.
AB  - Acetohydroxyacid synthase (AHAS; EC 2.2.1.6) catalyses the formation of 2
      acetolactate and 2-aceto-2-hydroxybutyrate as the first step in the biosynthesis
      of the branched-chain amino acids valine, leucine and isoleucine. The enzyme is
      inhibited by a wide range of substituted sulfonylureas and imidazolinones and
      many of these compounds are used as commercial herbicides. Here, the
      crystallization and preliminary X-ray diffraction analysis of the catalytic
      subunit of Arabidopsis thaliana AHAS in complex with the sulfonylurea herbicide
      chlorimuron ethyl are reported. This is the first report of the structure of any
      plant protein in complex with a commercial herbicide. Crystals diffract to 3.0 A
      resolution, have unit-cell parameters a = b = 179.92, c = 185.82 A and belong to
      space group P6(4)22. Preliminary analysis indicates that there is one monomer in
      the asymmetric unit and that these are arranged as pairs of dimers in the
      crystal. The dimers form a very open hexagonal lattice, with a high solvent
      content of 81%.

PMID- 14684915
TI  - Crystallization and X-ray analysis of the N-terminal core domain of a tumour
      associated human DEAD-box RNA helicase, rck/p54.
AB  - The RCK gene was cloned on the basis of the t(11;14)(q23;q32) chromosome
      translocation observed in human B-cell lymphoma cell line RC-K8. This gene was
      found to be overexpressed in various kinds of tumours. The gene product, rck/p54,
      consisting of 472 amino-acid residues with molecular weight 53.2 kDa, belongs to
      the family of DEAD-box RNA helicases. Its ATP-dependent RNA-unwinding activity
      toward c-myc RNA molecules in vitro has recently been demonstrated. In the
      present study, limited proteolysis experiments of rck/p54 were used to truncate
      the N-terminal domain (residues 1-288; 31.8 kDa) of rck/p54, leading to
      successful crystallization of Nc-rck/p54, i.e. the N-terminal core domain
      (residues 70-288; 24.5 kDa) of rck/p54. Crystals of Nc-rck/p54 were grown to a
      size suitable for X-ray structure analysis using polyethylene glycol 3350 as the
      precipitant. The crystal belongs to the orthorhombic space group P2(1)2(1)2(1),
      with unit-cell parameters a = 65.5, b = 73.1, c = 84.8 A, and diffracts X-rays to
      beyond 2.0 A resolution.

PMID- 14684916
TI  - Crystallization and preliminary X-ray crystallographic investigations on several
      thermostable forms of a Bacillus subtilis lipase.
AB  - Bacillus subtilis lipase loses activity above pH 10.5 and below pH 6.0. However,
      at low pH, i.e. below pH 5.0, the lipase acquires remarkable thermostability.
      Activity was unaltered for 2 h at 323 K at pH 4.0-5.0, although at pH values
      above 7.0 the activity was lost rapidly within minutes. Circular-dichroism
      studies indicate significant changes in the tertiary structure of the lipase,
      whereas the secondary-structural content remained unaltered. To elucidate the
      structural basis of the enhanced thermostability, three different forms have been
      crystallized at low pH along with three crystal forms of two thermostable mutants
      obtained using a directed-evolution approach.

PMID- 14684917
TI  - Crystallization and preliminary X-ray characterization of Trichoderma reesei
      hydrophobin HFBII.
AB  - Hydrophobins are small proteins found in filamentous fungi and characterized by
      their ability to change the character of a surface by spontaneous self-assembly
      on a hydrophobic-hydrophilic interface. Hydrophobin HFBII from Trichoderma reesei
      was crystallized by the hanging-drop vapour-diffusion method at 293 K. Two
      crystal forms were obtained: a native form and a form crystallized in the
      presence of manganese chloride. The native crystals were of high symmetry, cubic
      I23, but only diffracted to 3.25 A. The crystals grown in the presence of
      manganese were monoclinic and diffracted to 1.0 A with a synchrotron-radiation
      source. The anomalous difference Patterson map calculated from the home
      laboratory data showed a strong single peak, possibly caused by manganese present
      in the crystallization solution.

PMID- 14684918
TI  - Expression, purification, crystallization and preliminary crystallographic
      analysis of a putative GTP-binding protein, YsxC, from Bacillus subtilis.
AB  - Bacillus subtilis YsxC has been putatively identified as a member of the GTP
      binding protein family. Gene-knockout/deletion analysis has suggested that this
      protein is essential for survival of the microorganism and hence may represent a
      target for the development of a novel anti-infective agent. The B. subtilis ysxC
      gene was cloned and the protein was overexpressed in Escherichia coli and
      subsequently purified. Using hanging-drop vapour-diffusion crystallization
      techniques, two different crystal forms of YsxC were obtained in the presence and
      absence of GDP and which have one and two copies of YsxC in the asymmetric unit,
      respectively. Both crystal forms diffract to beyond 2.0 A resolution and are
      suitable for structure determination.

PMID- 14684919
TI  - Crystallization and preliminary X-ray diffraction analysis of the catalytic
      domain of recombinant human phosphodiesterase 3B.
AB  - The catalytic domain of human phosphodiesterase 3B has been cloned, expressed in
      Escherichia coli and purified in the presence of the PDE3 inhibitors IBMX (3
      isobutylmethylxanthine) or MERCK1 by affinity chromatography. Initial screening
      of crystallization conditions for these complexes in the hanging-drop vapor
      diffusion mode resulted in three different crystal forms, all characterized by
      quite large unit-cell parameters, elevated solvent content and poor diffraction
      quality. Subsequent optimization of these conditions led to crystals that
      diffract to 2.4 A and belong to space group C2, with unit-cell parameters a =
      146.7, b = 121.5, c = 126.3 A, beta = 100.6 degrees. Rotation-function analysis
      indicates that the asymmetric unit contains four copies of the monomeric enzyme,
      corresponding to a solvent content of 64%. To solve the structure of the PDE3B
      catalytic domain, molecular replacement as well as multiple isomorphous
      replacement methods are currently being utilized.

PMID- 14684920
TI  - Crystallization of a carbamatase catalytic antibody Fab fragment and its complex
      with a transition-state analogue.
AB  - Catalytic antibodies showing carbamatase activity have significant potential in
      antibody-directed prodrug therapy against tumours. The Fab fragment of an IgG1
      mouse monoclonal carbamatase catalytic antibody JC1 raised against a transition
      state analogue, ethyl N-(3,5-dicarboxyphenyl)-P-[N-[5'-(2",5"-dioxo-1"
      pyrrolidinyl)oxy-1',5'-dioxopentyl]-4-aminophenylmethyl]phosphonamidate, was
      obtained by digestion of the whole antibody with papain and was purified by two
      step ion-exchange chromatography. Using hanging-drop vapour-diffusion
      crystallization techniques, three different crystal forms of the Fab fragment
      were obtained in the presence and absence of the transition-state analogue. All
      crystals diffract X-rays to between 3.5 and 3.2 A resolution. The two crystal
      forms grown in the presence of the transition-state analogue contain up to four
      or eight copies of the Fab in the asymmetric unit and diffract to 3.5 and 3.2 A,
      respectively. The crystal of the Fab alone is most likely to contain only two
      copies of the Fab in the asymmetric unit and diffracts to beyond 3.5 A.
      Determination of the structure will provide insights into the active-site
      arrangement of this antibody and will help to increase our understanding of the
      molecular mechanisms by which the immune system can evolve catalytic function.

PMID- 14684921
TI  - Crystallization of the oligopeptide-binding protein AppA from Bacillus subtilis.
AB  - AppA is the membrane-anchored extracellular receptor component of an ABC
      transporter responsible for the uptake of oligopeptides into Bacillus subtilis.
      AppA has been overexpressed as a cleavable maltose-binding protein fusion in
      Escherichia coli. Following removal of the fusion portion, AppA has been
      crystallized from morpholinoethanesulfonic acid-buffered solutions at pH 6.5
      containing polyethylene glycol and zinc acetate. A complete X-ray diffraction
      data set extending to 2.3 A spacing has been collected.

PMID- 14684922
TI  - Expression, purification, crystallization and preliminary X-ray studies of
      geranylgeranyl diphosphate synthase from Thermus thermophilus HB8.
AB  - Geranylgeranyl diphosphate (GGPP) synthase from Thermus thermophilus HB8 was
      expressed in Escherichia coli, purified to homogeneity and crystallized both as
      the recombinant native protein and its selenomethionine (SeMet) derivative. Well
      diffracting crystals of these proteins were obtained belonging to the tetragonal
      space group P4(1) or P4(3), with unit-cell parameters a = b = 139.88, c = 73.37
      A. There were two homodimers in the asymmetric unit. A native data set was
      collected to 1.55 A resolution and a data set suitable for MAD phasing was
      collected to 2.40 A resolution on beamline BL40B2 at SPring-8.

PMID- 14684923
TI  - Crystallization and preliminary X-ray diffraction analysis of levansucrase (LsdA)
      from Gluconacetobacter diazotrophicus SRT4.
AB  - The endophytic bacterium Gluconacetobacter diazotrophicus SRT4 secretes a
      constitutively expressed levansucrase (LsdA; EC 2.4.1.10), which converts sucrose
      to fructo-oligosaccharides and levan. Fully active LsdA was purified to high
      homogeneity by non-denaturing reversed-phase HPLC and was crystallized at room
      temperature by the hanging-drop vapour-diffusion method using ammonium sulfate
      and ethanol as precipitants. The crystals are extremely sensitive, but native
      data have been collected to 2.5 A under cryogenic conditions using synchrotron
      radiation. LsdA crystals belong to the orthorhombic space group P22(1)2(1) or
      P2(1)2(1)2, with unit-cell parameters a = 53.80, b = 119.39, c = 215.10 A.

PMID- 14684924
TI  - The purification, crystallization and preliminary structural characterization of
      PhzF, a key enzyme in the phenazine-biosynthesis pathway from Pseudomonas
      fluorescens 2-79.
AB  - Phenazines produced by members of several bacterial genera are biologically
      active metabolites that function in microbial competitiveness, the suppression of
      soil-borne plant diseases and virulence in infectious disease. Despite recent
      progress towards understanding the biochemistry of phenazine synthesis, the key
      reactions leading to the formation of the heterocyclic scaffold common to all
      phenazine compounds remain obscure. Pseudomonas fluorescens 2-79 contains seven
      phenazine (phz) genes that encode components of the pathway for biosynthesis of
      phenazine-1-carboxylic acid. A central step in this pathway involves the
      condensation of two identical precursor molecules derived from chorismic acid and
      is catalysed by the product of the phzF gene. In this study, recombinant PhzF was
      purified and crystallized from PEG 4000/ammonium sulfate/sodium citrate pH 5.6.
      The crystals belong to space group P3(1)21 or P3(2)21, with unit-cell parameters
      a = b = 56.3, c = 156.4 A. They contain one monomer in the asymmetric unit and
      diffract to better than 1.7 A on synchrotron beamlines. Crystals of seleno-L
      methionine-labelled PhzF have been obtained and SAD data are reported.

PMID- 14684925
TI  - Purification, characterization and preliminary crystallographic studies of a
      cysteine protease from Pachyrrhizus erosus seeds.
AB  - The proteins Spe31 and Spe32, named after their respective molecular weights of
      about 31 and 32 kDa, were purified simultaneously from the seeds of Pachyrrhizus
      erosus. They cannot be separated from each other by column chromatography. N
      terminal sequence analysis indicated that they belonged to the papain family of
      cysteine proteases. An in-gel activity assay revealed that Spe31 possesses
      proteolytic activity while Spe32 only displays very weak activity for protein
      degradation. Both of them are glycoproteins as detected by the periodic acid and
      Schiff's reagent method. Crystals were obtained from the protein mixture by the
      hanging-drop vapour-diffusion method; they diffracted to a resolution of 2.61 A
      on an in-house X-ray source. The crystals belong to space group P4(1(3))2(1)2,
      with unit-cell parameters a = b = 61.96, c = 145.61 A. Gel electrophoresis under
      non-denaturing conditions showed that the protein crystallized was Spe31.

PMID- 14684926
TI  - Crystallization of the pectate lyase PelI from Erwinia chrysanthemi and SAD
      phasing of a gold derivative.
AB  - The pectate lyase PelI is involved in the degradation of plant tissues by the
      phytopathogenic bacterium Erwinia chrysanthemi. It has been crystallized from a
      solution containing PEG 550 in the space group P2(1), with unit-cell parameters a
      = 61.6, b = 70.7, c = 73.4 A, beta = 112.8 degrees. Crystals diffract to 1.45 A
      using synchrotron radiation. SAD phases have been computed from a gold-derivative
      crystal at the wavelength of maximum absorption (L(III) edge).

PMID- 14684927
TI  - Purification, crystallization and preliminary X-ray diffraction studies on
      pyruvate phosphate dikinase from maize.
AB  - Pyruvate phosphate dikinase (PPDK) from maize catalyzes the reversible conversion
      of ATP, orthophosphate and pyruvate to AMP, pyrophosphate and PEP. In higher
      plants, this enzyme is believed to be involved in the C(4) dicarboxylic acid
      pathway. PPDK was crystallized by the vapour-diffusion method using polyethylene
      glycol as a precipitant. The crystals belong to the orthorhombic space group C2,
      with unit-cell parameters a = 108.2, b = 100.2, c = 108.4 A, beta = 96.5 degrees,
      and diffract to 2.3 A using SPring-8 synchrotron radiation.

PMID- 14684928
TI  - Rhombohedral crystals of Mycobacterium tuberculosis phosphopantetheine
      adenylyltransferase.
AB  - The penultimate step of prokaryotic coenzyme A (CoA) biosynthesis is directed by
      the essential enzyme phosphopantetheine adenylyltransferase (PPAT; EC 2.7.7.3),
      an attractive target for antibiotics. The reaction catalyzed by PPAT is rate
      limiting and involves the transfer of an adenylyl group from ATP to 4'
      phosphopantetheine to form 3'-dephospho-CoA. Rhombohedral crystals of PPAT from
      Mycobacterium tuberculosis (Rv2965c) were obtained. The crystals belong to space
      group R32, with unit-cell parameters a = 68.69 A, alpha = 91.81 degrees. The
      crystals diffract to better than 2 A resolution on a Cu Kalpha rotating-anode
      generator. The packing density for one polypeptide chain in the asymmetric unit
      is 2.89 A(3) Da(-1), with a solvent content of 0.57.

PMID- 14684929
TI  - Crystallization and preliminary X-ray diffraction analysis of pyranose 2-oxidase
      from the white-rot fungus Trametes multicolor.
AB  - Pyranose 2-oxidase (P2Ox) is a 270 kDa homotetrameric flavoenzyme that catalyzes
      the oxidation of D-glucose to 2-keto-D-glucose. P2Ox participates in lignin
      degradation by white-rot fungi and a tentative role of the enzyme is the
      production of H(2)O(2) for lignin peroxidases. Crystals of Trametes multicolor
      P2Ox were grown from monomethylether PEG 2000, sodium acetate, MgCl(2) and
      Ta(6)Br(12). They belong to space group P2(1), with unit-cell parameters a =
      99.9, b = 101.7, c = 135.6 A, beta = 90.85 degrees. X-ray diffraction data to 2.0
      A resolution were collected using synchrotron radiation. Self-rotation function
      calculations suggest that the asymmetric unit contains one homotetramer with 222
      point-group symmetry.

PMID- 14684930
TI  - W3Y single mutant of rubredoxin from Pyrococcus furiosus: a preliminary time-of
      flight neutron study.
AB  - Rubredoxin from the hyperthermophilic archaeon Pyrococcus furiosus maintains its
      native structure at high temperatures (373 K). In order to investigate the role
      of hydrogen bonding, hydration and chain dynamics in this thermostability,
      wavelength-resolved Laue neutron diffraction data have been collected from the
      W3Y single mutant (Trp3-->Tyr3) on the spallation neutron protein crystallography
      station (PCS) at Los Alamos Neutron Science Center. Data were measured at room
      temperature from nine crystal settings, each of approximately 12 h duration. The
      total data-measurement period was less than 5 d from a single crystal that had
      undergone H(2)O/D(2)O exchange. The nominal resolution of the data is 2.1 A.

PMID- 14684931
TI  - An improved protocol for rapid freezing of protein samples for long-term storage.
AB  - Freezing of purified protein drops directly in liquid nitrogen is a convenient
      technique for the long-term storage of protein samples. Although this enhances
      reproducibility in follow-up crystallization experiments, some protein samples
      are not amenable to this technique. It has been discovered that plunging PCR
      tubes containing protein samples into liquid nitrogen results in more rapid
      freezing of the samples and can safely preserve some proteins that are damaged by
      drop-freezing. The PCR-tube method can also be adapted to a PCR-plate freezing
      method with applications for high-throughput and structural genomics projects.

PMID- 14684933
TI  - Tissue parasites in patients with chronic urticaria.
AB  - Chronic urticaria is an important diagnostic and therapeutic problem. We aimed to
      investigate the sero-prevalence of tissue parasites causing toxocariasis and
      fasciolosis in patients with chronic urticaria. All cases were analyzed for
      antibodies against Toxocara canis and Fasciola hepatica by modified (homemade)
      ELISA. The excretory/secretory products of Toxocara and Fasciola were used as
      antigens (ES-ELISA) in the test. In this study, the highest toxocariasis
      seropositivity (29.0%) rate and the highest fasciolosis seropositivity (14.5%)
      rate were found in patients with chronic urticaria. Fasciolosis seropositivity
      and total seropositivity of toxocariasis and fasciolosis in patients with chronic
      urticaria was significantly higher than in healthy controls (p<0.05).
      Toxocariasis seropositivity in patients with chronic urticaria was not
      significantly higher than that in healthy controls (p>0.05). We suggest that
      parasitic infections should be considered as an important cause of chronic
      urticaria. Serological methods should be used to expose the diagnosis of tissue
      parasites in such cases.

PMID- 14684934
TI  - Pemphigus in Korea: clinical manifestations and treatment protocol.
AB  - Pemphigus, a rare, chronic blistering disease of the skin and mucous membranes
      with severe morbidity and occasional mortality, is the most common autoimmune
      bullous disease in Korea. The purpose of this study was to evaluate the clinical
      features and propose a treatment strategy for patients with pemphigus. A
      retrospective analysis was conducted of 51 pemphigus patients seen between 1993
      and 2001. Pemphigus vulgaris (PV) was the most common type with 32 cases,
      followed by 19 cases of pemphigus foliaceus (PF). The male to female ratio was
      1:1.3, with females predominating, particularly among PV patients (PV, 1:1.5; PF,
      1:1.1). The average ages at onset of PV and PF were 44.3 and 51.0 years old,
      respectively. Mucosal involvement was noted in 27 cases (84.4%) of PV but in only
      3 cases (15.8%) of PF. Most patients initially received relatively low to
      intermediate doses (0.3-1.0 mg/kg/day) of prednisolone, and 23 (71.9%) PV
      patients and 10 (52.6%) PF patients also received immunosuppressive agents. Oral
      prednisolone and azathioprine (100 mg/day) formed the mainstay of treatment for
      our patients (47.1%). At the time of writing, 25.5% (13/51) of patients are in
      complete remission, and 72.5% (37/51) are undergoing maintenance therapy. One
      patient died due to sepsis during the treatment. For the treatment of pemphigus,
      a course of the lowest possible corticosteroid dosage in combination with
      immunosuppressive agents appears to be effective and less toxic than a high
      corticosteroid dosage.

PMID- 14684935
TI  - Ultraviolet-B phototherapy is successful in Japanese patients with early-stage
      mycosis fungoides.
AB  - UVB phototherapy is widely used for the treatment of psoriasis and atopic
      dermatitis, however, only limited reports evaluate its usefulness in the
      treatment of mycosis fungoides. We introduced UVB phototherapy to five patients
      with early-stage mycosis fungoides. All of them were classified as stage IB
      (erythematous stage), and none had obtained a satisfactory response to other
      therapies. After initial treatment with UVB phototherapy, all the patients
      obtained significant improvement in their skin lesions leaving pigmentary
      changes. After this satisfactory response was achieved, the same dose of UVB was
      administrated as a maintenance therapy with longer intervals between exposures.
      Histopathological examination of three patients revealed decreased numbers of
      inflammatory cells in both the epidermis and the dermis after the treatment.
      Immunohistochemical study showed that CD1a+/HLA-DR+ dendritic cells were present
      throughout the lesional epidermis before the treatment. In contrast, after the
      treatment, the dendritic cells in the epidermis were CD1a+/HLA-DR-. Although it
      remains unclear why only the expression of HLA-DR antigen was eliminated after
      treatment, we presume that this loss of HLA-DR antigen expression by epidermal
      Langerhans cells was, in part, responsible for the improvement of skin lesions.
      This preliminary study suggests that UVB phototherapy is an effective treatment
      for patients with early-stage mycosis fungoides.

PMID- 14684936
TI  - Acute allergic contact dermatitis due to para-phenylenediamine after temporary
      henna painting.
AB  - The use of temporary natural henna painting for body adornment and hair dyeing is
      very common in several countries of the Indian subcontinent, Middle East, and
      North Africa, and the fad is spreading in other parts of the world. Several cases
      of para-phenylenediamine (PPD) contaminated, temporary traditional/natural henna
      induced sensitization and acute allergic reaction have been reported, along with
      occasional serious long term and rare fatal consequences. We report here a 17
      year-old girl with blisters over her hands of five-days duration that appeared
      within 72 hours of applying a temporary henna paint to her hands during a social
      occasion. Similar lesions were noted on her face. She had previously applied
      black henna only once, a year earlier without developing any lesions. Clinical
      diagnosis of acute allergic contact dermatitis (ACD) was made. After a short
      course of oral corticosteroids, topical mometasone furaote 1.0% cream, and oral
      antihistamines, the lesions healed completely over the next four weeks leaving
      post-inflammatory hypopigmentation. Patch testing done with standard European
      battery, PPD 1% in petrolatum, and commercially available natural henna powder
      revealed a 3+ reaction to PPD at 48 hours. No reaction was seen at the natural
      henna site. Awareness of the condition among physicians and the public and
      regulation regarding warnings of the risks of using such products is urgently
      warranted.

PMID- 14684937
TI  - Iatrogenic hypercalcemia due to vitamin D3 ointment (1,24(OH)2D3) combined with
      thiazide diuretics in a case of psoriasis.
AB  - Tacalcitol is a synthetic vitamin D3 analogue developed for topical treatment of
      inflammatory skin diseases such as psoriasis. Hypercalcemia has not been
      previously reported during treatment with topical tacalcitol. We experienced a
      male patient with psoriasis and hypertension whose conditions were treated with
      tacalcitol ointment and thiazide, respectively, resulting in hypercalciuria and
      hypercalcemia. After initiation of topical vitamin D3 ointment (20 micro g/g of
      tacalcitol) 10 g/day for the skin lesions, both the serum level of calcium and
      urinary excretion of calcium increased gradually. On day 28 of the treatment, his
      serum calcium levels had reached 3.55 mmol/l, and his urinary calcium excretion
      had also increased from 0.008 g/day to 0.475 g/day. The tacalcitol treatment was
      terminated, seven days later, the serum calcium level had returned to the
      reference range without any specific treatment. The present case is the first
      report of hypercalcemia induced by vitamin D3 ointment and thiazide
      simultaneously.

PMID- 14684938
TI  - The successful use of topical tacrolimus treatment for a chronic actinic
      dermatitis patient with complications of idiopathic leukopenia.
AB  - Chronic actinic dermatitis (CAD) is a photosensitivity disorder marked by severe
      eczematous lesions on exposed areas. Although associations with contact
      dermatitis, atopic dermatitis, and human immunodeficiency virus (HIV) have been
      suggested, its pathogenesis remains unknown. CAD is often refractory, and
      systemic administration of cyclosporin A has been the treatment of choice.
      Recently, topical tacrolimus therapy has been reported to be effective. We report
      the efficacy of topical tacrolimus treatment in a CAD patient who also had the
      complication of idiopathic leukopenia. A phototest showed marked suppression of
      erythema formation in the skin pre-treated with tacrolimus before UVB radiation
      but not in the skin treated after the irradiation. Therefore, it is suggested
      that tacrolimus may prevent UV-B induced erythema by suppressing a very early
      phase of the inflammatory process in CAD.

PMID- 14684939
TI  - Churg-Strauss syndrome (CSS) manifested as necrosis of fingers and toes and liver
      infarction.
AB  - We report a case of Churg-Strauss syndrome (CSS) with necrosis of the fingers and
      toes and liver infarction. A 59-year-old man with asthma suddenly noticed that
      his fingers and toes felt unusually cold. This condition worsened progressively,
      and some digits became necrotic within several weeks. Laboratory studies revealed
      hypereosinophilia and an extremely elevated serum level of IgE. Digital
      subtraction angiography of the extremities revealed extensive irregular narrowing
      of small and medium-sized arteries in the extremities. Abdominal computed
      tomography (CT) revealed an area of low density at the periphery of the right
      lobe of the liver. Angiography revealed irregular narrowing of small arteries
      that corresponded to the ischemic area. A nerve conduction study suggested
      sensory nerve neuropathy. The preceding asthma, acute onset of digital necrosis,
      liver infarction, neuropathy, and hypereosinophilia strongly suggested a
      diagnosis of CSS. The patient was treated with 40 mg of prednisolone and 120
      micro g of intravenous prostaglandin E1 daily, and all the digits that had turned
      black and necrotic were amputated. After the amputation, the dose of prednisolone
      was gradually reduced, and no new lesions appeared on the skin or in the liver.
      The rare possible complications of CSS, including necrosis of digits and liver
      infarction, should not be ignored.

PMID- 14684940
TI  - X-linked dominant inheritance in palmoplantar keratoderma with leukokeratosis: a
      study of the pedigree of two cases.
AB  - Keratoderma of the palms and soles is not of rare occurrence. Its association
      with leukokeratosis of the mouth is well recognized. We describe two siblings
      having callosities like keratoderma over the weight bearing areas of soles,
      pressure areas of palms and palmar creases with leukokeratosis of cheeks. On
      study of the pedigree of these probands we could trace the trait transmission by
      a rare X-linked dominant mechanism.

PMID- 14684941
TI  - Basal cell carcinomas of the areola-nipple complex: case reports and review of
      the literature.
AB  - Two white men 57 and 39 years old, and a 47-year-old white woman were seen with
      slowly developing papulo-nodular lesions of the areola-nipple complex. None of
      the patients presented with regional lymphadenopathy, history of trauma, or
      relevant sun-exposure. After excison of the mass, the histologic diagnosis of
      basal cell carcinoma was made. At two years of follow-up, no recurrence was
      evident. The low incidence of basal cell carcinoma in this particular site allows
      us to consider the areola-nipple complex location as unusual. Moreover,
      literature reports do not suggest that these BCCs have an increased potential for
      malignancy. The treatment options depend on the extension of the tumor and on the
      possible involvement of the areola-nipple complex and mammary tissue.

PMID- 14684942
TI  - Glomangiosarcoma of the hand: a case report and review of the literature.
AB  - Glomangiosarcomas, or malignant glomus tumors, are very rare, cutaneous, soft
      tissue tumors. Despite having histologic features of malignancy, these tumors
      usually do not metastasize. We describe a 74-year-old woman with a
      glomangiosarcoma on her hand and review the literature. The woman presented with
      a five month history of a painful mass on the right palm. An excisional biopsy of
      the mass was undertaken. Histologically, the tumor was composed of uniform, round
      cells and numerous vascular components. The tumor cells were pleomorphic and had
      large nucleoli. Frequent mitotic figures were identified. Immunohistochemical
      stains showed strong positivity for vimentin and weak, focal positivity for
      smooth muscle actin. Ultrastructurally, the tumor cells were characterized by
      pinocytic vesicles, well formed basal lamina, and scattered junctional complex of
      the plasma membrane.

PMID- 14684943
TI  - Lipoma of the index finger.
AB  - Lipomas are common, benign tumors originating from adipose tissues. They can
      occur anywhere on the body but are rarely found on the finger. We report two
      lipomas of the right index finger in a 46-year-old man; this is the first report
      of a lipoma occurring on the fingers in Korea.

PMID- 14684944
TI  - Response to article "Depression circumstantially related to the administration of
      finasteride for androgenetic alopecia" (J Dermatol, 29, 665-669, 2002).

PMID- 14684946
TI  - Exfoliative dermatitis induced by leflunomide therapy.

PMID- 14684947
TI  - Mite-antigen induced immediate reactions in atopic dermatitis are inhibited by
      daily administration of fexofenadine.

PMID- 14684948
TI  - Autologous punch grafting for repigmentation in piebaldism.

PMID- 14684949
TI  - Multiple piloleiomyomas: do they follow dermatomes or blaschko lines?

PMID- 14684950
TI  - Solitary eccrine syringofibroadenoma.

PMID- 14684951
TI  - Residual washing detergent in cotton clothes: a factor of winter deterioration of
      dry skin in atopic dermatitis.
AB  - Although it is well known that the skin in patients with atopic dermatitis
      becomes drier in winter, the mechanisms of winter deterioration of dry skin are
      not fully understood. Our purpose was to determine whether residual washing
      detergent in cotton clothes plays a role in the winter deterioration of atopic
      dry skin. We studied 148 Japanese patients with atopic dermatitis who visited our
      dermatology clinic during winter months. They wore cotton underwear, which they
      had washed in cold tap water. We examined the distribution of dry skin on their
      trunks. We then asked them to stop washing their clothes with common anionic,
      additive-enriched detergents, and to use a nonionic, additive-reduced detergent
      for a period of two weeks. Photographs of 2 or 3 representative dry skin sites on
      the trunk were taken before and after the trial. By comparing the before-after
      trial photographs, the severity of dry skin at the end of the trial was assessed
      on a 5-point scale ranging from markedly improved to worsened. Of the 148
      patients examined, 115 (78%) had widespread or localized dry skin on the trunk.
      The dryness of the skin was prominent around the shoulders. Of these 115
      patients, 87 (76%) showed marked or moderate improvement of dry skin after the
      two-weeks of use of the nonionic, additive-reduced washing detergent. No patient
      showed worsening of the dry skin. These results suggest that residues of common
      washing detergents in cotton underclothes play an important role in the winter
      deterioration of dry skin in patients with atopic dermatitis who use cold tap
      water for washing their clothes.

PMID- 14684952
TI  - Immediate and delayed complications of dexamethasone cyclophosphamide pulse (DCP)
      therapy.
AB  - Dexamethasone-cyclophosphamide pulse (DCP) is the prefered mode of therapy in
      pemphigus in India because it is relatively free from the side effects seen with
      heavy doses of daily oral steroids. One hundred forty-six pemphigus patients
      treated with DCP were observed for side effects of this regimen. One hundred
      forty mg of dexamethasone was administered IV in 200 ml of 5% dextrose over a
      period of 60-90 minutes on 3 consecutive days. Five hundred mg of
      cyclophosphamide was added on first day of the pulse and 50 mg given orally daily
      in the intervening period. DCP was repeated every 4 weeks and continued for 6
      months after subsidence of the disease (no new lesions). Flushing over the face
      was the most common event recorded during the adiministration in 78 subjects
      followed by palpitations in 11, hiccups in 9, and numbness of feet in 6. Fourteen
      patients had polyurea, and 3 developed skin rash. Shivering, shooting pains along
      thighs, breathlessness, seizure and unilateral limb edema were observed in one
      patient each. Generalized weakness/malaise was the most troublesome delayed side
      effect in 81 (55.4%) patients; it lasted for 8-15 days after the pulse. Thirty
      six (24.6%) had inadequate sleep syndrome, 23 (15.7%) had headache, 21 (14.3%)
      complained of arthralgias, 19 (13%) experienced alteration in taste, and 13 (9%)
      had diffuse hair loss. 28 females developed menstrual disturbances, and 14 (9.5%)
      had blurring of vision (glaucoma in 3 and posterior subcapsular cataract in 1).
      Thirteen of eighteen diabetics had an increase in blood sugar requiring higher
      doses of insulin. Five NIDDM patients needed insulin. Four (2.7%) developed
      hypertension. Pulse therapy is not absolutely free from side effects.
      Hypertension and diabetes occur less frequently as compared to conventional
      steroid therapy. Generalized weakness, flushing, headache and taste alteration
      occur exclusively with pulse therapy.

PMID- 14684953
TI  - Estrogen dermatitis that appeared twice in each menstrual period.
AB  - A 23-year-old woman presented with millet-sized red papules that were scattered
      over her chest and abdomen. She stated that since the age of 20, she had
      recurrently suffered from pruritic eruptions that coincided with ovulation and
      the time prior to menstruation, and that they persisted for a few days before
      vanishing spontaneously leaving some pigmentation. A skin biopsy specimen
      revealed spongiotic bullae in the epidermis and marked infiltration of
      lymphocytes accompanied by some histiocytes and eosinophils in the upper dermis.
      An intradermal test for conjugated estrogen showed an urticarial reaction that
      faded in about four hours. Although the test did not strictly meet the criterion
      (erythema to remain for more than 24 hours for papulovesicular eruptions), it was
      concluded that the timing of the episodes along with the result of the test
      suggested that a diagnosis of estrogen dermatitis was highly probable. There have
      been several reports of this condition since it was first reported as a distinct
      entity in 1995; but whatever the reasons, the flares were observed only before
      menstruation in these cases, despite the fact that the serum estrogen levels
      showed a double-peaked pattern during each menstrual period. This is considered
      to be a rare case of estrogen dermatitis that flared twice in each menstrual
      period. Limited improvement was noted in the symptoms even without treatment.

PMID- 14684954
TI  - A case of acute generalized exanthematous pustulosis (AGEP) possibly induced by
      iohexol.
AB  - Acute generalized exanthematous pustulosis (AGEP) is an uncommon disease
      manifested as an erythematous pustular eruption. It is usually caused by systemic
      medication. We describe a patient with acute generalized pustular eruption
      induced by iohexol. A 52-year-old woman developed fever and a generalized
      pustular eruption on the neck, trunk and extremities three days after taking
      iohexol. The culture from pustules was sterile. Other systemic and laboratory
      examinations were normal. A skin biopsy from a lesion on the trunk showed the
      features of a drug-induced pustular eruption as a subcorneal blister including
      neutrophils and eosinophils, mild spongiosis, and a sparse infiltrate at
      neutrophils and eosinophils in the papillary dermis. The patient had no history
      of psoriasis. The lesions resolved with systemic corticosteroid therapy within
      one week and did not relapse. According to our investigation, iohexol-induced
      AGEP has not been previously reported. We present an interesting case.

PMID- 14684955
TI  - Localized cutis marmorata telangiectatica congenita on the back of a young man.
AB  - We report the clinical and light microscopic features of a case of cutis
      marmorata telangiectatica congenita with a painful refractory ulcer that was
      found on the back of a young Japanese man. The ulcer was positioned on the upper
      back over the spinal bone. In addition to the anatomical location of the ulcer,
      the vascular ectases may have played a part in the refractory ulceration.

PMID- 14684956
TI  - Successful treatment of multiple premalignant and malignant lesions in arsenical
      keratosis with a combination of acitretin and intralesional 5-fluorouracil.
AB  - A case of arsenical keratosis with multiple lesions of Bowen's disease and
      squamous cell carcinoma is described. The patient was successfully treated with a
      combination of acitretin and intralesional 5-fluorouracil. All the lesions
      resolved after three months of therapy with no side effects and no recurrence
      during four months of follow-up.

PMID- 14684957
TI  - Nasal natural killer/T cell lymphoma with cutaneous involvement: case report and
      Chinese literature review reported in China mainland.
AB  - Nasal natural killer (NK)/T cell lymphoma is an Epstein-Barr virus (EBV)
      associated lymphoma that arises in the nasal area and aggressively invades
      surrounding tissues. Our patient was a 48-year-old male who had had nasal
      obstruction and nasal discharge for 2 years and infiltrating plaques and necrosis
      on his nasal dorsum for three months. He developed fever and fatigue two weeks
      before admission. Biopsy from both skin and nasal mucosa revealed atypical medium
      sized tumor cells infiltrating into the dermis. Immunohistochemical studies
      revealed that the tumor cells were UCHL-1, cytoplasmic CD3, CD56, TIA-1, and
      granzyme B positive, and CD8 and CD20 negative. In situ hybridization for EBV-DNA
      was positive. Clonal TCRb and TCRg gene rearrangement were negative. The patient
      was treated with cyclophosphamide, vincristine, and prednisone (COP) and with
      local radiotherapy, but he died 20 days later. We reviewed the cases of nasal
      NK/T cell lymphoma reported in mainland China in the Chinese literature during
      the last 5 years.

PMID- 14684958
TI  - Pulse therapy with amikacin and dapsone for the treatment of actinomycotic foot:
      a case report.
AB  - Actinomycetoma is a chronic disease caused by aerobic actinomycetes and affecting
      the skin, subcutaneous tissue, and bones. It causes significant morbidity and
      clinically manifests as abscesses and sinus/fistulae with or without granules.
      Early diagnosis is based on the color, size, histopathology of the granules;
      culture and metabolic studies are used for further species differentiation.
      Although sulfamethoxazole-trimethoprim alone or in combination with dapsone for a
      variable period of time are used as first line agents for treatment, slow
      response to the therapy and high relapse rates have led to increasing usage of
      alternative agents like gentamycin, amikacin and cefotaxime. We report a case of
      actinomycetoma foot who had complete treatment failure with a sulfamethoxazole
      trimethoprim-dapsone combination and was successfully treated with combination
      therapy of amikacin and dapsone without any side effects.

PMID- 14684959
TI  - Reticulate acropigmentation of dohi: first case reports from Nepal.
AB  - Acropigmentation of Dohi is a rare acropigmentary disorder. We report two cases
      of reticulate acropigmentation of Dohi from Nepal. To the best of our knowledge,
      these two cases represent the first case reports from Nepal.

PMID- 14684960
TI  - A case of solitary indeterminate cell histiocytosis.

PMID- 14684961
TI  - A unique case of palmoplantar keratoderma.

PMID- 14684962
TI  - Evaluation of graded strength glycolic acid (GA) facial peel: an Indian
      experience.

PMID- 14684963
TI  - A case of prurigo-type drug eruptions due to UFT.

PMID- 14684964
TI  - Recurrent herpes simplex-2 infection on the palm.

PMID- 14684965
TI  - Perinatal development of the rat kidney: apoptosis and epidermal growth factor.
AB  - Localization of apoptotic cells in the kidney of perinatal rats was examined by
      the terminal deoxynucleotidyl transferase-mediated d-UTP-biotin nick end labeling
      (TUNEL) method and electron microscopy. Perinatal changes in the percentage of
      kidney cells with DNA fragmentation were determined by flow cytometric analysis.
      Through observation of two successive sections, the relationship between the
      localization of the epidermal growth factor receptor (EGFR) positive cells and
      TUNEL positive cells in the kidney was determined. From fetal day 18 to neonatal
      day 5, TUNEL positive cells were noted in immature glomeruli, collecting ducts
      and interstitium. Electron microscopically, chromatin condensed nuclei and
      apoptotic bodies were seen in the same tissue component as the TUNEL positive
      cells. The percentage of DNA fragmented cells significantly increased from fetal
      days 18 to 20 and significantly decreased from fetal days 20 to 22, while they
      still remained low in the neonatal period. The TUNEL positive cells in immature
      glomeruli and collecting ducts were not reactive to the EGFR antibody. The TUNEL
      positive cells were not observed in the proximal tubular cells, which were
      positive to EGFR antibody. These results indicate that apoptotic cells are
      present in the kidney throughout the perinatal period in the rat and that EGF
      plays an important role in perinatal development of the rat kidney.

PMID- 14684966
TI  - Infertility observed in female rats treated with N-acetyl-L-cysteine:
      Histopathological examination of ovarian follicles and recovery of fertility.
AB  - We previously reported infertility in female rats that received N-acetyl-L
      cysteine (NAC) intravenously at a dosage of 1000 mg/kg/day. Unfertilized oocytes
      and gestation day 1 and 2 embryos were assessed morphologically, and the results
      suggested that absence or thinning of the zona pellucida (ZP) is related to
      infertility. However, the morphological characteristics of oocytes before
      ovulation and recovery from the effects of NAC were not clarified. In the present
      study, the ovarian follicles were histopathologically examined and the recovery
      of reproductive function was evaluated to investigate the effects of NAC. Female
      Sprague-Dawley rats at 10 weeks of age received NAC intravenously at 1000
      mg/kg/day for more than 1 week. Thinning of the ZP was observed in the ovarian
      follicles in all stages of growth by light microscopy. Outflow of the components
      of the ZP between the corona radiata and disarrangement of the corona radiata
      were more pronounced in growing follicles than in large secondary follicles.
      Similar findings were observed by electron microscopy, and the effects of NAC
      were limited to the ZP. Infertility and thinning of the ZP were observed in the
      no-recovery NAC group, but not in the recovery NAC group, in which animals
      recovered within four estrous cycles after NAC administration. It has been
      reported that the ZP is expressed by oocytes or by both oocytes and granulosa
      cells, but no changes were noted in these cells. The present findings suggest
      that NAC affects the ZP directly and that reproductive function may recover from
      the effects of NAC.

PMID- 14684967
TI  - An improved technique for repeated gavage administration to rat neonates.
AB  - The technique for gavage administration to rat nurslings was improved to allow
      determination of the direct effects of chemical substances in the nurslings. Rat
      neonates were treated with distilled water from postnatal day 1 through 20 using
      this technique. The viability of neonates during the administration period was
      comparable to that of untreated neonates. No adverse effects of this technique on
      the development of neonates were found, and no histological alterations of the
      esophagus or pharynx. Therefore, we conclude that use of our improved gavage
      administration method will contribute to ensuring successful neonatal development
      and thus allowing accurate assessment of the toxicological effects of test
      compounds on rat nurslings.

PMID- 14684968
TI  - VACTERL association with a cleft hand.
AB  - Regarding radial ray deficiency, several reports suggest that preaxial limb
      anomalies occur frequently, while postaxial limb anomalies and cleft hand (split
      hands) are rarely associated with VACTERL. We describe a rare clinical case of
      VACTERL with cleft hand and a number of visceral anomalies.

PMID- 14684970
TI  - Antibacterial activity of polyphenol components in oolong tea extract against
      Streptococcus mutans.
AB  - The purpose of the present study was to determine the antibacterial activity of
      oolong tea extract on oral streptococci, including Streptococcus mutans and
      Streptococcus sobrinus, and to identify the response to its components.
      Antibacterial activity was found when the extract was added to S. mutans cells in
      chemically defined medium but not in complex broth media. Further, pretreatment
      with bovine serum albumin reduced the antibacterial activity. The extract showed
      antibacterial activity against all of the oral streptococci examined, with the
      highest activity against S. mutans MT8148R. This activity was found to originate
      from a monomeric polyphenol-rich fraction, and it was stronger than that of pure
      polyphenols. Moreover, some combinations of monomeric polyphenols showed the
      highest level of antibacterial activity. These results suggest that the
      antibacterial activity of oolong tea extract is caused by a synergistic effect of
      monomeric polyphenols, which can easily bind to proteins.

PMID- 14684971
TI  - The effects of egg-derived antibodies to glucosyltransferases on dental caries in
      rats.
AB  - The role of Streptococcus mutans in the development of dental caries is well
      recognized. Important virulence factors include the glucosyltransferases (gtf),
      essential for production of glucans. We evaluated the anticariogenic effects of
      orally administered chicken anti-cell-associated (CA) Gtf antibodies in
      desalivated rats. The animals were infected with S. mutans MT8148R and treated
      with chicken anti-CA-Gtf egg yolk antibodies (IgY) or nonimmune egg yolk powder.
      Smooth surface lesions were significantly lower in the anti-CA-Gtf-treated group
      in comparison to the control groups. Sulcal surface caries was also decreased and
      of less severity. Our study suggests that chicken anti-CA-Gtf antibodies may have
      promise as a prophylaxis for high caries risk patients.

PMID- 14684972
TI  - Oral fluoride retention in saliva following toothbrushing with child and adult
      dentifrices with and without water rinsing.
AB  - Ten healthy adult volunteers were recruited to participate in this double-blind
      randomised 18-leg crossover designed study. The subjects either rinsed their
      mouth with 10 ml de-ionised distilled water for 10 s or just spat out once after
      1-min brushing with one of nine different toothpastes: NaF (500, 1,000 and 1,450
      ppm F), SMFP (525, 1,000, 1,450 ppm F), AmF (250, 1,400 ppm F) or fluoride-free
      dentifrice. Samples of whole mixed unstimulated saliva were collected at
      different time intervals. The results showed that the use of the AmF toothpaste
      (1,400 ppm F) resulted in the highest fluoride content of saliva without water
      rinsing after 120 min (0.52 ppm F, CI 0.23, 0.81). Two hours after brushing with
      fluoride toothpaste containing AmF and NaF, the salivary fluoride levels were
      still higher than baseline levels.

PMID- 14684973
TI  - Prevalence and determinants of enamel fluorosis in Flemish schoolchildren.
AB  - As part of an epidemiological study on the oral health of Flemish schoolchildren,
      fluoride use was studied together with risk factors (medical history, tap water
      fluoride concentration, use of fluoride supplements, toothpaste and brushing
      habits). Fluorosis was scored according to the Thylstrup-Fejerskov index (TFI) in
      children aged 11 years (4,128 children examined). Explanatory variables were
      recorded yearly, starting at the age of 7. Earliest toothpaste use was reported
      at the age of 1. By age 7, 99.7% of the children reported the use of toothpaste
      (90% fluoride-containing), but only 13.9% reported using a pea-sized amount. At
      age 7, 66% of the children had received systemic fluoride supplements during at
      least part of their childhood. At 11 years, 92% of the children used a fluoride
      containing toothpaste and 6% still received systemic fluoride supplements.
      Fluorosis was present in about 10% of all the children examined, mainly TFI score
      1 (7.3% in upper central incisors). Logistic regression established tooth
      brushing frequency and fluoride supplement use, in addition to tap water fluoride
      concentrations above 0.7 mg/l, as significant risk factors when the presence of
      fluorosis on at least one tooth was used as outcome variable. Children having
      fluorosis had a lower risk of caries, both in the primary (median dmft 1, range 0
      10 vs. 2, range 0-12) and permanent dentition (median DMFT 0, range 0-5 vs. 0,
      range 0-11).

PMID- 14684974
TI  - Is attention-deficit hyperactivity disorder a risk factor for dental caries? A
      case-control study.
AB  - Experience in practice has suggested that children with attention-deficit
      hyperactivity disorder (ADHD) tend to have higher numbers of diseased, missing
      and filled teeth (DMFT score) than children without the condition. To date,
      however, this impression has not been systematically investigated. A case-control
      study of children in Otago, New Zealand (case DMFT > or = 5; control DMFT <5;
      case status determined from School Dental Service dental records) was conducted
      by postal survey and reference to the School Dental Service records. Cases and
      controls were matched on age, sex, ethnicity, and school socio-economic status.
      The purpose of the study was to assess whether having ADHD was associated with
      higher odds of having high caries experience. Questionnaires were returned for a
      total of 128 case-control pairs. Conditional logistical regression analysis
      showed that, after controlling for fluoride history, medical problems, diet, and
      self-reported oral hygiene, children with ADHD had nearly 12 times the odds of
      having a high DMFT score than children who did not have ADHD (OR = 11.98; 95% CI
      1.13, 91.81). No other factors were significant predictors. Dental practitioners
      and parents should consider ADHD to be a condition that may affect children's
      dental caries experience.

PMID- 14684975
TI  - Relationship between histological and radiographic caries lesion depth measured
      in images from four digital radiography systems.
AB  - The aim of this study was to compare the accuracy of approximal caries lesion
      depth measurements in radiographs from four digital systems. Two CCD-based
      sensors, Dixi (Planmeca) and Sidexis (Sirona), and two phosphor plate systems,
      Digora (Soredex) and DenOptix (Gendex), were used to record radiographs of 177
      extracted human teeth. Sixty-four radiographically visible lesions were selected
      and measured by 4 observers in the digital radiographs and in digital photographs
      of histological sections of the teeth. The gold standard (true measure) was
      defined as the mean of the 4 observers' measurements on the histological
      sections. Two untrained observers underestimated general lesion depth in all the
      radiographic systems while each of 2 trained observers underestimated the depth
      in one of the systems. Analysis of variance revealed that Digora images resulted
      overall in the smallest underestimation, followed by Dixi, DenOptix and Sidexis.
      The differences between Digora and Sidexis and between Dixi and Sidexis were
      statistically significant (p < 0.05). Analysis of variance using the regression
      coefficient as the test variable demonstrated that the coefficients differed
      between DenOptix and the remaining systems (p < 0.05) while there were no
      significant differences between these (p > 0.05). It can be concluded that
      radiographs obtained with the Dixi and Digora systems were more accurate than
      Sidexis and DenOptix images for measurement of caries lesion depth. Still, a high
      probability exists that the individual lesion measurement is either overestimated
      or underestimated compared to the true lesion depth.

PMID- 14684976
TI  - Effect of imaging geometry on evaluating natural white-spot lesions using
      quantitative light-induced fluorescence.
AB  - The objective of this study was to determine the effect of imaging geometry on
      evaluating natural white-spot lesions with quantitative light-induced
      fluorescence (QLF). A total of 34 specimens were prepared from extracted human
      premolars and permanent molars with white spots on the interproximal surface. The
      specimens were each adjusted to a final thickness of 3.0 mm. Images were acquired
      with the QLF system perpendicular to the white spots and at 5 degrees intervals
      up to 30 degrees above and below the perpendicular. The specimens were rotated
      around the buccolingual axis of the tooth (pitch angle) and around the long axis
      of the tooth (roll angle). The averages of fluorescence loss (DeltaF, %) and
      lesion size (mm2) were determined with QLF. Another variable, DeltaQ, which was
      defined as the fluorescence loss integrated over the lesion size (% x mm2), was
      also calculated. DeltaF was smaller when lesions were viewed from the cervical
      direction (angles less than 90 degrees ), and became bigger when viewed from the
      coronal direction. Roll angle did not significantly affect DeltaF. Apparent
      lesion size diminished with deviations from 90 degrees in both directions for
      pitch and roll angles. DeltaQ was affected by pitch and roll angles with the
      largest value at 90 degrees and values decreasing in both directions from 90
      degrees. In general, there were significant differences for angles larger than 20
      degrees from the perpendicular for all three QLF variables. This study suggests
      that angle is an important factor to control when performing QLF studies;
      however, small changes (deviations within 20 degrees ) have a minimal effect on
      QLF variables.

PMID- 14684977
TI  - In vitro assessment of methods of applying the electrical caries monitor for the
      detection of occlusal caries.
AB  - The aim of this in vitro study was to assess the diagnostic performance of five
      methods of using the Electrical Caries Monitor (ECM) to detect caries lesions at
      enamel and dentine thresholds in occlusal molar surfaces with and without stain.
      Histological validation was performed in 152 occlusal sites in permanent molar
      teeth. For the sites without stain the areas under the ROC curve (AUC) for the
      five methods ranged from 0.69 to 0.93 (enamel) and 0.74 to 0.92 (dentine). For
      stained sites the AUC ranged from 0.59 to 0.65 (enamel) and 0.66 to 0.77
      (dentine). The performance of the ECM was reduced in the presence of stain. The
      measurements using toothpaste as a conducting medium were generally worse than
      when direct measurements were taken. The profiles of the resistance curves
      generated as the tooth was dried for 5 s were used to derive additional summary
      variables. The AUC for all sites using an outcome variable generated from these
      data were 0.89 (enamel) and 0.91 (dentine), respectively, for all teeth. It is
      concluded that the performance of the ECM might be improved by either considering
      a combination of variables or using different resistance cut-offs in the presence
      or absence of stain.

PMID- 14684978
TI  - Demineralization of dentin by Streptococcus mutans biofilms grown in the constant
      depth film fermentor.
AB  - To develop a bacterial demineralization model, we grew Streptococcus mutans
      biofilms in a constant depth film fermentor (CDFF) and studied the effects of
      sucrose pulsing frequency (SPF) in time on dentin demineralization. S. mutans
      biofilms were grown in dentin specimens with grooves and on dentin surface
      specimens for 20 days. During the experiments, 2% sucrose was pulsed either 4 or
      8 times per day for periods of 30 min. Diluted brain-heart infusion medium
      containing 25 mM PIPES buffer and 1.5 mM CaCl2 was pulsed as the alternative
      growth medium. Specimens with intact biofilms were taken out on days 5, 12 and
      20. The model was assessed by viable counts of the biofilm, mineral loss and
      lesion depth in the dentin specimens (by transversal microradiography) and pH
      measurements in the groove (by pH microelectrode). The results showed that
      biofilms formed on the dentin surface specimens were constant in viable counts
      for the low SPF, while this parameter tended to increase with time under the high
      SPF. Lesions with intact surfaces were formed and the lesion size increased
      significantly over time and increased significantly with increasing SPF. Typical
      Stephan curves were found after sucrose pulsing. The pH inside the groove
      returned to neutral under low SPF, but remained below 6.5 under high SPF. With
      the CDFF S. mutans biofilm model, lesions can be created in dentin within
      reasonable experimental time periods, as a result of the presence of a biofilm
      and in response to carbohydrate challenges.

PMID- 14684979
TI  - Brushing abrasion of softened and remineralised dentin: an in situ study.
AB  - The aim of the present in situ study was to evaluate the effect of different
      periods of intra-oral remineralisation on the susceptibility of softened dentin
      to toothbrushing abrasion. Groups of 6 human dentin specimens (A-F) were recessed
      in the buccal aspects of intra-oral appliances which were worn for 21 days by 11
      volunteers. The samples were demineralised twice a day extra-orally in the acidic
      beverage Sprite Light (pH 2.9) for 90 s. Subsequently, the dentin specimens were
      brushed at different times. Specimen A was brushed immediately after
      demineralisation. Specimens B-E were brushed after the intra-oral appliances had
      been worn for various periods in the mouth: specimen B for 10 min, C for 20 min,
      D for 30 min and E for 60 min. Specimen F was not brushed (control). After 21
      days, dentin wear was measured with a profilometer. The following values (means
      +/- standard deviation) were recorded (microm): A, 23.6 +/- 16.7; B, 37.9 +/-
      29.7; C, 31.8 +/- 26.5; D, 18.5 +/- 10.5; E, 15.3 +/- 11.6; F, 12.6 +/- 6.7.
      There was a statistically significantly increased dentin loss for groups A, B and
      C as compared to the controls (U test: p < 0.05). However, after intra-oral
      periods of 30 and 60 min, wear was not significantly higher than in unbrushed
      controls. It is concluded that for protection of dentin surfaces at least 30 min
      should elapse before toothbrushing after an erosive attack.

PMID- 14684980
TI  - Scanning electron microscopy of softened enamel.
AB  - After exposing enamel specimens to 0.3% citric acid at pH 3.2 for various times,
      the acid was titrated to pH 7 before rinsing the specimens in water. After freeze
      drying the specimens were examined by scanning electron microscopy. This
      procedure eliminates artefacts due to drying and mineral precipitation. The
      results showed that the outer region of softened enamel is much more delicate
      than previously thought, even after short (5- to 20-min) etching times. Mineral
      was lost from both prism boundaries and the prism bodies, resulting in a surface
      presenting thin, separate crystal bundles. In further studies, replicas of
      subsurface pores, created by resin impregnation, showed the softening depth to be
      several times greater than is suggested by techniques based on removing the
      softened enamel by physical forces. The results point to a need for improved
      methods of measuring softening depth. More importantly, it appears that the outer
      region of the softened layer remaining after an erosive challenge might be too
      fragile to resist frictional forces in vivo.

PMID- 14684981
TI  - Microcomputed tomographic assessment of chemomechanical caries removal.

PMID- 14684982
TI  - Turning on the male--SRY, SOX9 and sex determination in mammals.
AB  - The decision of the bi-potential gonad to develop into either a testis or ovary
      is determined by the presence or absence of the Sex-determining Region gene on
      the Y chromosome (SRY). Since its discovery, almost 13 years ago, the molecular
      role that SRY plays in initiating the male sexual development cascade has proven
      difficult to ascertain. While biochemical studies of clinical mutants and mouse
      genetic models have helped in our understanding of SRY function, no direct
      downstream targets of SRY have yet been identified. There are, however, a number
      of other genes of equal importance in determining sexual phenotype, expressed
      before and after expression of SRY. Of these, one has proven of central
      importance to mammals and vertebrates, SOX9. This review describes our current
      knowledge of SRY and SOX9 structure and function in the light of recent key
      developments.

PMID- 14684983
TI  - Expression studies of the PIS-regulated genes suggest different mechanisms of sex
      determination within mammals.
AB  - In mammals, the Y-located SRY gene is known to induce testis formation from the
      indifferent gonad. A related gene, SOX9, also plays a critical role in testis
      differentiation in mammals, in birds and reptiles. It is now assumed that SRY
      acts upstream of SOX9 in the sex determination cascade, but the regulatory link
      which should exist between these two genes remains unknown. Studies on XX sex
      reversal in polled goats (PIS mutation: Polled Intersex Syndrome) have led to the
      discovery of a female-specific locus crucial for ovarian differentiation. This
      genomic region is composed of at least two genes, FOXL2 and PISRT1, which share a
      common transcriptional regulatory region, PIS. In this review, we present the
      expression pattern of these PIS-regulated genes in mice. The FOXL2 expression
      profile of mice is similar to that described in goats in accordance with a
      conserved role of this ovarian differentiating gene in mammals. On the contrary,
      the PISRT1 expression profile is different between mice and goats, suggesting
      different mechanisms of the primary switch in the testis determination process
      within mammals. A model based on two different modes of SOX9 regulation in mice
      and other mammals is proposed in order to integrate our results into the current
      scheme of gonad differentiation.

PMID- 14684984
TI  - Structure, evolution and expression of the FOXL2 transcription unit.
AB  - FOXL2 is a putative transcription factor involved in ovarian development and
      function. Its mutations in humans are responsible for the blepharophimosis
      syndrome, characterized by eyelid malformations and premature ovarian failure
      (POF). Here we have performed a comparative sequence analysis of FOXL2 sequences
      of ten vertebrate species. We demonstrate that the entire open reading frame
      (ORF) is under purifying selection leading to strong protein conservation. We
      also review recent data on FOXL2 transcript and protein expression. FOXL2 has
      been shown 1) to be the earliest known sex dimorphic marker of ovarian
      determination/differentiation in vertebrates, 2) to have, at least in mammals, an
      ovarian expression persisting until adulthood. The conservation of its sequence
      and pattern of expression suggests that FOXL2 might be a key factor in the early
      development of the vertebrate female gonad and involved later in adult ovarian
      function. Finally, we provide arguments for the existence of an alternative
      transcript in rodents, that may arise from a differential polyadenylation.
      Although it has only been demonstrated in rodents, its presence/absence in other
      species deserves further investigation.

PMID- 14684985
TI  - Origin and possible roles of the SOX8 transcription factor gene during sexual
      development.
AB  - SOX8 is a member of the SOX family of developmental transcription factor genes
      and is closely related to SOX9, a critical gene involved in mammalian sex
      determination and differentiation. Both genes encode proteins with the ability to
      bind similar DNA target sequences, and to activate transcription in in vitro
      assays. Expression studies indicate that the two genes have largely overlapping
      patterns of activity during mammalian embryonic development. A knockout of SOX8
      in mice has no obvious developmental phenotype, suggesting that the two genes are
      able to act redundantly in a variety of developmental contexts. In particular,
      both genes are expressed in the developing Sertoli cell lineage of the developing
      testes in mice, and both proteins are able to activate transcription of the gene
      encoding anti-Mullerian hormone (AMH), through synergistic action with
      steroidogenic factor 1 (SF1). We have hypothesized that SOX8 may substitute for
      SOX9 in species where SOX9 is expressed too late to be involved in sex
      determination or regulation of AMH expression. However, our studies involving the
      red-eared slider turtle indicate that SOX8 is expressed at similar levels in
      males and females throughout the sex-determining period, suggesting that SOX8 is
      neither a transcriptional regulator for AMH, nor responsible for sex
      determination or gonad differentiation in that species. Similarly, SOX8 is not
      expressed in a sexually dimorphic pattern during gonadogenesis in the chicken.
      Since a functional role(s) for SOX8 is implied by its conservation during
      evolution, the significance of SOX8 for sexual and other aspects of development
      will need to be uncovered through more directed lines of experimentation.
      Copyright 2003 S. Karger AG, Basel

PMID- 14684986
TI  - Cell aggregation precedes the onset of Sox9-expressing preSertoli cells in the
      genital ridge of mouse.
AB  - SOX9 is expressed at the onset of the genital ridge formation in both sexes. It
      is assumed that SRY, the testis determining gene, turns SOX9 on in male embryos
      because it is turned off in female embryos. Spatial expression of SRY follows a
      cranio-caudal pattern. Here, we asked if SOX9 is expressed in the same cell
      lineage and with a similar pattern as SRY. A correlative study between the
      structural changes in the genital ridge and the immunocytochemical localization
      of SOX9-positive cells was undertaken. We used a transgenic strain expressing the
      green fluorescent protein (GFP) that considerably enhanced the cell context where
      the first SOX9-positive cells appear. Although SOX9-positive cells are located
      among loose mesenchymal cells by stages of 8-14 tail somites (ts) in both sexes,
      they are absent in the thickening coelomic epithelium of females. At 15 ts the
      first SOX9-positive cells appear within the core of the condensed cells only in
      male genital ridges. At 17 ts, a gradient of SOX9-positive cells in males is
      apparent, closely following the cranio-caudal pattern of cell aggregation seen in
      genital ridges of both sexes. Hence, our results suggest that SOX9 is expressed
      only in loose mesenchymal cells in both sexes and that expression of SOX9 in
      males requires the prior aggregation of cells in the genital ridges. The
      correspondence of SOX9 and SRY pattern of expression supports that both genes are
      expressed in the preSertoli cell lineage in the core of the genital ridges.

PMID- 14684987
TI  - Isolation of chromosomal regions controlling intersex development in a marsupial.
AB  - A marsupial (Sminthopsis douglasi) with bilateral intersexuality had a
      hemiscrotum on the right side and a hemi-pouch with nipples on the left. A normal
      female karyotype (2n = 14, XX) was present in cells from the right (male) side,
      while cells from the left (female) side initially had a female karyotype plus two
      dot-like chromosomes (2n = 14, XX + 2B). It is proposed that the dots represented
      a region deleted from the X chromosome that contains the "pouch-mammary/scrotum"
      (PMS) switch gene whose dosage determines development of a pouch and teats (two
      doses) or a scrotum (one dose). Mis-segregation early in embryonic development
      produced a lineage with one normal X and one deleted X (male side), and a lineage
      with a normal and deleted X, plus two copies of the deleted region (female side).
      The origin of the supernumerary elements was therefore investigated in the
      expectation that they may contain the long-sought pouch-mammary/scrotum switch
      gene. Several elements were microdissected, and amplified DNA was used for in
      situ hybridization, producing signals in five different chromosome regions
      including the X. This could represent a region of the X that contains, as well as
      PMS, repetitive DNA that is present also at other chromosomal sites.

PMID- 14684988
TI  - Expression of DMRT1 in the mammalian ovary and testis--from marsupials to mice.
AB  - Doublesex and mab3 related transcript (DMRT1) was identified as a candidate gene
      for human 9p24.3 associated sex reversal. DMRT1 orthologues have highly conserved
      roles in sexual differentiation from flies and worms to humans. A DMRT1
      orthologue was isolated from a marsupial, the tammar wallaby Macropus eugenii.
      The wallaby gene is highly conserved with other vertebrate DMRT1 genes,
      especially within the P/S and DM domains. It is expressed in the differentiating
      testis from the late fetus, during pouch life and in the adult. As in eutherian
      mammals, DMRT1 protein was localized in the germ cells and the Sertoli cells of
      the testis, but in addition it was detected in the Leydig cells, peri-tubular
      myoid cells and within the acrosome of the sperm heads. DMRT1 protein was also
      detected in the fetal and adult ovary pre-granulosa, granulosa and germ cells.
      Similarly, we also detected DMRT1 in the granulosa cells of all developing
      follicles in the adult mouse ovary. This is the first report of DMRT1 expression
      in the adult mammalian ovary, and suggests a wider role for this gene in mammals,
      in both the testis and ovarian function.

PMID- 14684989
TI  - Protein transduction as a strategy for evaluating important factors in mammalian
      sex determination and differentiation.
AB  - Protein transduction is a powerful tool to deliver biologically active protein
      into mammalian cells and whole animals. Transduced proteins are folded properly
      and can mediate their respective functions in their hosts. To examine the
      feasibility of applying this strategy to study the molecular events of
      gonadogenesis, we have studied the kinetics of protein transduction and stability
      of transduced protein in in vitro mouse gonad culture systems using two reporter
      proteins, TAT-beta-gal and beta-gal fusion proteins with and without the TAT
      protein transduction domain (PTD) respectively. Our results indicate that the TAT
      PTD was critical and essential for protein transduction to cultured fetal gonads.
      The TAT-beta-gal reporter entered the cells of the gonads and mesonephros
      efficiently for both sexes at E11.5 to E15.5 stages examined. The delivered
      protein persisted in the gonads for an extended period after an initial one-hour
      transduction. The distribution of the reporter was relatively even in gonads and
      mesonephros at E11.5 stage for both sexes and at later stages in female. The
      transduced protein was distributed heterogeneously in male gonads after
      seminiferous tubule differentiation in which the amount of reporter protein was
      higher outside than inside the tubules. Nevertheless, we surmise that such
      protein delivery technique should be useful in studies designed to evaluate the
      sex determining or differentiating functions of various new protein factors
      identified by advanced differential screening strategies.

PMID- 14684990
TI  - Molecular characterization of three gonad cell lines.
AB  - To facilitate the study of the regulation and downstream interactions of genes
      involved in gonad development it is important to have a suitable cell culture
      model. We therefore aimed to characterize molecularly three different mouse gonad
      cell lines. TM3 and TM4 cells were originally isolated from prepubertal mouse
      gonads and were tentatively identified as being of Leydig cell and Sertoli cell
      origin, respectively, based upon their morphology and hormonal responses. The
      third line is a conditionally immortalized cell line, derived from 10.5-11.5 days
      post-coitum (dpc) male gonads of transgenic embryos carrying a temperature
      sensitive SV40 large T-antigen. We studied by reverse transcription-polymerase
      chain reaction (RT-PCR) the expression profiles of a number of genes known to be
      important for early gonad development. Moreover, we assessed these cell lines for
      their capacity to induce SOX9 transcription upon expression of SRY, a key
      molecular event occurring during sex determination. We found that all three cell
      lines were unable to upregulate SOX9 expression upon transfection of SRY
      expression constructs, even though these cells express many of the studied
      embryonic gonad genes. These observations point to a requirement for SRY
      cofactors for direct or indirect upregulation of SOX9 expression during testis
      determination.

PMID- 14684991
TI  - Expression pattern of a gonadoblastoma candidate gene suggests a role of the Y
      chromosome in prostate cancer.
AB  - The contribution of specific genes on the Y chromosome in the etiology of
      prostate cancer has been undefined. Genetic mapping studies have identified a
      gonadoblastoma locus on the human Y chromosome (GBY) that predisposes the
      dysgenetic gonads of XY sex-reversed patients to tumorigenesis. Recently a
      candidate gene, the testis-specific protein Y-encoded (TSPY) that resides on the
      GBY critical region, has been demonstrated to express preferentially in tumor
      cells in gonadoblastoma and testicular germ cell tumors. TSPY shares high
      homology to a family of cyclin B binding proteins and has been considered to
      possibly play a role in cell cycle regulation or cell division. To address the
      possible involvement of the TSPY gene in prostate cancer, both in situ mRNA
      hybridization and immunohistochemistry techniques were used to study the
      expression of this putative GBY gene in prostate specimens. Our results
      demonstrated that TSPY was expressed at low levels in normal epithelial cells and
      benign prostatic hyperplasia (BPH), but at elevated levels in tumor cells of
      prostate cancers at various degrees of malignancy. Sequence analysis of RT-PCR
      products obtained from both prostatic and testicular tissues using specific
      primers flanking the open reading frame of the TSPY mRNA revealed a complex
      pattern of RNA processing of the TSPY transcripts involving cryptic intron
      splicing and/or intron skipping. The variant transcripts encode a variety of
      polymorphic isoforms or shortened versions of the TSPY protein, some of which
      might possess different biochemical and/or functional properties. The abbreviated
      transcripts were more abundant in prostatic cancer tissues than the testicular
      ones. Although the exact nature of such variant TSPY transcripts and proteins is
      still unclear, their differential expression suggests that the TSPY gene may also
      be involved in the multi-step prostatic oncogenesis besides its putative role in
      gonadoblastoma and testicular seminoma.

PMID- 14684992
TI  - Dppa3 is a marker of pluripotency and has a human homologue that is expressed in
      germ cell tumours.
AB  - We identified a transcript named 11M2 on the basis of its strong male-specific
      expression pattern in the developing mouse gonad. 11M2 was found to be expressed
      by gonad primordial germ cells (PGCs) of both sexes and down-regulated in female
      PGCs as they enter prophase I of the first meiotic division, similar to the
      expression of OCT4. Mouse EST analysis revealed expression only in early-stage
      embryos, embryonic stem cells and pre-meiotic germ cells. 11M2 corresponds to a
      recently reported gene variously known as PGC7, STELLA or DPPA3. We have
      identified the human orthologue of DPPA3 and find by human EST analysis that it
      is expressed in human testicular germ cell tumours but not in normal human
      somatic tissues. The expression patterns of mouse and human DPPA3, in
      undifferentiated embryonic cells, embryonic germ cells and adult germ cell
      tumours, together suggest a role for this gene in maintaining cell
      pluripotentiality.

PMID- 14684993
TI  - Sex chromosomes, sex determination, and sex-linked sequences in Microtidae.
AB  - The Arvicolidae is a widely distributed rodent group with several interesting
      characteristics in their sex chromosomes. Here, we summarize the actual knowledge
      of some of these characteristics. This mammalian group has species with abnormal
      sex determination systems. In fact, some species present the same karyotype in
      both males and females, with total absence of a Y chromosome, and hence of SRY
      and ZFY genes. Other species present fertile, sex-reversed XY females, generally
      due to mutations affecting X chromosomes. Furthermore, in Microtus oregoni males
      and females are gonosomic mosaic (the females are XO in the soma and XX in the
      germ cells, while the males are XY in the soma and OY in the germ cells).
      Regarding sex chromosomes, some species present enlarged (giant) sex chromosomes
      because of the presence of large blocks of constitutive heterochromatin, which
      have been demonstrated to be highly heterogeneous. Furthermore, we also consider
      the alterations affecting composition and localization of sex-linked genes or
      repeated sequences. Finally, this rodent group includes species with synaptic and
      asynaptic sex chromosomes. In fact, several species with asynaptic sex
      chromosomes have been described. It is interesting to note that within the genus
      Microtus both types of sex chromosomes are present.

PMID- 14684994
TI  - The rice field eel as a model system for vertebrate sexual development.
AB  - Complex developmental mechanisms of vertebrates are unraveled using comparative
      genomic approaches. Several teleosts, such as zebrafish, medaka and pufferfish,
      are used as genetic model systems because they are amenable to studies of gene
      function. The rice field eel, a freshwater fish, is emerging as a specific model
      system for studies of vertebrate sexual development because of its small genome
      size and naturally occurring sex reversal. Data presented here support the use of
      the rice field eel as another important fish model for comparative genome
      studies, especially in vertebrate sexual development. This model system is
      complementary rather than redundant.

PMID- 14684995
TI  - Sex and death in birds: a model of dosage compensation that predicts lethality of
      sex chromosome aneuploids.
AB  - Birds show female heterogamety, with ZZ males and ZW females. It is still not
      clear whether the W is female-determining, or whether two doses of the Z
      chromosomes are male-determining, or both. This question could easily be settled
      by the sexual phenotypes of ZZW and ZO birds, in the same way that the sexual
      phenotypes of XXY and XO showed that the Y is male determining in humans, but
      that the dosage of an X-borne gene determines sex in Drosophila. However, despite
      extensive searches, no ZZW or ZO diploid birds have been satisfactorily
      documented, so we must assume that these genotypes are embryonic lethals. Given
      that ZW and ZZ are viable and the W contains few genes it is not clear why this
      should be so. Here I propose that sex chromosome aneuploids are lethal in chicken
      because, to achieve dosage compensation, a locus on the W chromosome controls the
      upregulation of genes on the Z in ZW females. ZO birds would therefore have only
      half the normal dose of Z-linked gene product and ZZW would have twice the
      amount, both of which would undoubtedly be incompatible with life. Reports of
      other aneuploids and triploids are also consistent with this hypothesis.

PMID- 14684996
TI  - Steroids, aromatase and sex differentiation of the newt Pleurodeles waltl.
AB  - In the newt Pleurodeles waltl, genetic sex determination obeys female
      heterogamety (female ZW, male ZZ). In this species as in most of non-mammalian
      vertebrates, steroid hormones play a key role in sexual differentiation of
      gonads. In that context, male to female sex reversal can be obtained by treatment
      of ZZ larvae with estradiol. Male to female sex reversal has also been observed
      following treatment of ZZ larvae with testosterone, a phenomenon that was called
      the "paradoxical effect". Female to male sex reversal occurs when ZW larvae are
      reared at 32 degrees C during a thermosensitive period (TSP) that takes place
      from stage 42 to stage 54 of development. Since steroids play an important part
      in sex differentiation, we focussed our studies on the estrogen-producing enzyme
      aromatase during normal sex differentiation as well as in experimentally induced
      sex reversal situations. Our results based on treatment with non-aromatizable
      androgens, aromatase activity measurements and aromatase expression studies
      demonstrate that aromatase (i) is differentially active in ZZ and ZW larvae, (ii)
      is involved in the paradoxical effect and (iii) might be a target of temperature.
      Thus, the gene encoding aromatase might be one of the master genes in the process
      leading to the differentiation of the gonad in Pleurodeles waltl.

PMID- 14684997
TI  - Induction of XY sex reversal by estrogen involves altered gene expression in a
      teleost, tilapia.
AB  - To clarify the importance of endogenous estrogens during sex differentiation in a
      teleost fish, the Nile tilapia, we examined the target events for endogenous
      estrogens and their role during gonadal sex differentiation. The expression of
      CYP19a (P450arom) precedes any morphological gonadal sex differentiation. Further
      to these findings, the treatment of XX fry with non-steroidal aromatase inhibitor
      (AI), Fadrozole, from seven to 14 days after hatching caused complete sex
      reversal to functional males. The XX sex reversal induced by AI was rescued
      completely with simultaneous estrogen treatment. We also found that XY fry
      treated with estrogen, before the appearance of morphological sex differences,
      caused complete sex reversal from males to females. Taken together, these results
      suggest that endogenous estrogens are required for ovarian differentiation. To
      identify the down-stream gene products of estrogen during ovarian
      differentiation, we performed subtractive hybridization using mRNA derived from
      normal and estrogen treated XY gonads. Two out of ten gene products were
      expressed in germ cells, whereas the others were expressed in somatic cells.

PMID- 14684998
TI  - Expression of Dmrt1 protein in developing and in sex-reversed gonads of
      amphibians.
AB  - Many genes are known to be involved in gonadal differentiation in vertebrates.
      Dmrt1, a gene that encodes a transcription factor with a DM-domain, is considered
      to be one of the essential genes controlling testicular differentiation in
      mammals, birds, reptiles, amphibians and fish. However, it still remains unknown
      which testicular cells of animals other than mice and chicks express Dmrt1
      protein. For an explanation of its role(s) in testicular differentiation in
      vertebrates, the expression of the Dmrt1 protein needs to be studied. For this
      purpose, we conducted an immunohistochemical study of this protein in an
      amphibian by using an antibody specific for Dmrt1. No positive signal was found
      in the indifferent gonad of tadpoles of Rana rugosa at early stages. However, in
      the testis of tadpoles at later stages (XV-XXV) and in frogs one month after
      metamorphosis, this protein was expressed in interstitial cells and Sertoli
      cells. In the testis of adult frogs, germ cells also expressed Dmrt1 protein. RT
      PCR analysis revealed that the gene for this protein was not transcribed at any
      time during ovarian development, but was expressed in the female to male sex
      reversed gonad. This was true when immunohistological studies were performed. In
      addition, Southern blot analysis showed DMRT1 to be an autosomal gene. Taken
      together, our findings indicate that Dmrt1 protein is expressed by interstitial
      cells, Seroli cells and germ cells in the testis of R. rugosa. Dmrt1 may thus be
      very involved in the testicular differentiation of amphibians.

PMID- 14684999
TI  - Expression of Dmrt1 in a turtle with temperature-dependent sex determination.
AB  - There is a variety of sex determining mechanisms among vertebrates. Many reptiles
      possess temperature-dependent sex determination (TSD), in which the incubation
      temperature of the egg determines the sex of the hatchling. The red-eared slider
      turtle, Trachemys scripta has often been used as a model system for examining the
      physiology of TSD. In the current study, the expression of Dmrt1 was examined
      during TSD in this turtle. Dmrt1 is a putative regulator of sex
      determination/differentiation and has been identified in a variety of
      vertebrates, including fishes, amphibians, reptiles, birds, and mammals.
      Specifically, Dmrt1 has been shown to be up-regulated in a male-specific pattern
      during embryonic development in many vertebrates. In the current study, the
      expression patterns of Dmrt1 were examined in the developing adrenal-kidney-gonad
      complexes of T. scripta during embryonic development. Using a quantitative
      competitive RT-PCR, Dmrt1 was shown to be up-regulated during the thermosensitive
      period of sex determination in males. In contrast, levels of Dmrt1 remained low
      in females throughout the thermosensitive period. These data suggest that the up
      regulation of Dmrt1 may play a role in male sex determination/sex differentiation
      during TSD in T. scripta.

PMID- 14685000
TI  - Differential Dmrt1 transcripts in gonads of the protandrous black porgy,
      Acanthopagrus schlegeli.
AB  - Black porgy, Acanthopagrus schlegeli Bleeker, is a marine protandrous
      hermaphrodite fish. A Dmrt1 cDNA was cloned and characterized and in order to
      study the process of sex change in this species, mRNA transcripts of Dmrt1 were
      monitored. Dmrt1 was specifically transcribed in testis and seminal vesicle in 2
      year-old black porgy according to RT-PCR and Southern analysis. A real-time
      quantification PCR analysis was further developed for the measurement of Dmrt1
      transcripts. Dmrt1 transcripts were at significantly higher levels in bisexual
      testis than bisexual ovary in 1+ and 2+ year-old fish. Dmrt1 transcripts
      decreased in the functional and bisexual testis of 3-year-old fish. Much higher
      levels of Dmrt1 transcripts in the bisexual ovary were detected in 1+ year-old
      fish than in 2+ and 3-year-old fish. No differences in Dmrt1 transcripts were
      found in bisexual ovaries of 2+ and 3-year-old fish and female ovaries of 3-year
      old fish. The data suggest there is relationship of Dmrt1 to the sex change of
      protandrous black porgy.

PMID- 14685001
TI  - Analysis of repetitive DNA sequences in the sex chromosomes of Oreochromis
      niloticus.
AB  - In the Nile tilapia, Oreochromis niloticus, sex determination is primarily
      genetic, with XX females and XY males. While the X and Y chromosomes (the largest
      pair) cannot be distinguished in mitotic chromosome spreads, analysis of
      comparative hybridization of X and Y chromosome derived probes (produced, by
      microdissection and DOP-PCR, from XX and YY genotypes, respectively) to different
      genotypes (XX, XY and YY) has demonstrated that sequence differences exist
      between the sex chromosomes. Here we report the characterization of these probes,
      showing that a significant proportion of the amplified sequences represent
      various transposable elements. We further demonstrate that concentrations of a
      number of these individual elements are found on the sex chromosomes and that the
      distribution of two such elements differs between the X and Y chromosomes. These
      findings are discussed in relation to sex chromosome differentiation in O.
      niloticus and to the changes expected during the early stages of sex chromosome
      evolution.

PMID- 14685002
TI  - Cortical orofacial motor representation in Old World monkeys, great apes, and
      humans. I. Quantitative analysis of cytoarchitecture.
AB  - Social life in anthropoid primates is mediated by interindividual communication,
      involving movements of the orofacial muscles for the production of vocalization
      and gestural expression. Although phylogenetic diversity has been reported in the
      auditory and visual communication systems of primates, little is known about the
      comparative neuroanatomy that subserves orofacial movement. The current study
      reports results from quantitative image analysis of the region corresponding to
      orofacial representation of primary motor cortex (Brodmann's area 4) in several
      catarrhine primate species (Macaca fascicularis, Papio anubis, Pongo pygmaeus,
      Gorilla gorilla, Pan troglodytes, and Homo sapiens) using the Grey Level Index
      method. This cortical region has been implicated in the execution of skilled
      motor activities such as voluntary facial expression and human speech. Density
      profiles of the laminar distribution of Nissl-stained neuronal somata were
      acquired from high-resolution images to quantify cytoarchitectural patterns.
      Despite general similarity in these profiles across catarrhines, multivariate
      analysis showed that cytoarchitectural patterns of individuals were more similar
      within-species versus between-species. Compared to Old World monkeys, the
      orofacial representation of area 4 in great apes and humans was characterized by
      an increased relative thickness of layer III and overall lower cell volume
      densities, providing more neuropil space for interconnections. These phylogenetic
      differences in microstructure might provide an anatomical substrate for the
      evolution of greater volitional fine motor control of facial expressions in great
      apes and humans.

PMID- 14685003
TI  - Cortical orofacial motor representation in Old World monkeys, great apes, and
      humans. II. Stereologic analysis of chemoarchitecture.
AB  - This study presents a comparative stereologic investigation of neurofilament
      protein- and calcium-binding protein-immunoreactive neurons within the region of
      orofacial representation of primary motor cortex (Brodmann's area 4) in several
      catarrhine primate species (Macaca fascicularis, Papio anubis, Pongo pygmaeus,
      Gorilla gorilla, Pan troglodytes, and Homo sapiens). Results showed that the
      density of interneurons involved in vertical interlaminar processing (i.e.,
      calbindin- and calretinin-immunoreactive neurons) as well pyramidal neurons that
      supply heavily-myelinated projections (i.e., neurofilament protein-immunoreactive
      neurons) are correlated with overall neuronal density, whereas interneurons
      making transcolumnar connections (i.e., parvalbumin-immunoreactive neurons) do
      not exhibit such a relationship. These results suggest that differential scaling
      rules apply to different neuronal subtypes depending on their functional role in
      cortical circuitry. For example, cortical columns across catarrhine species
      appear to involve a similar conserved network of intracolumnar inhibitory
      interconnections, as represented by the distribution of calbindin- and calretinin
      immunoreactive neurons. The subpopulation of horizontally-oriented wide-arbor
      interneurons, on the other hand, increases in density relative to other
      interneuron subpopulations in large brains. Due to these scaling trends, the
      region of orofacial representation of primary motor cortex in great apes and
      humans is characterized by a greater proportion of neurons enriched in
      neurofilament protein and parvalbumin compared to the Old World monkeys examined.
      These modifications might contribute to the voluntary dexterous control of
      orofacial muscles in great ape and human communication.

PMID- 14685004
TI  - Brain architecture and social complexity in modern and ancient birds.
AB  - Vertebrate brains vary tremendously in size, but differences in form are more
      subtle. To bring out functional contrasts that are independent of absolute size,
      we have normalized brain component sizes to whole brain volume. The set of such
      volume fractions is the cerebrotype of a species. Using this approach in mammals
      we previously identified specific associations between cerebrotype and behavioral
      specializations. Among primates, cerebrotypes are linked principally to
      enlargement of the cerebral cortex and are associated with increases in the
      complexity of social structure. Here we extend this analysis to include a second
      major vertebrate group, the birds. In birds the telencephalic volume fraction is
      strongly correlated with social complexity. This correlation accounts for almost
      half of the observed variation in telencephalic size, more than any other
      behavioral specialization examined, including the ability to learn song. A
      prominent exception to this pattern is owls, which are not social but still have
      very large forebrains. Interpolating the overall correlation for Archaeopteryx,
      an ancient bird, suggests that its social complexity was likely to have been on a
      par with modern domesticated chickens. Telencephalic volume fraction outperforms
      residuals-based measures of brain size at separating birds by social structure.
      Telencephalic volume fraction may be an anatomical substrate for social
      complexity, and perhaps cognitive ability, that can be generalized across a range
      of vertebrate brains, including dinosaurs.

PMID- 14685007
TI  - Valproic-acid-induced thrombocytopenia and hepatotoxicity: discontinuation of
      treatment?
AB  - We report the case of a 4-year-old boy with long-term sodium valproate (valproic
      acid; VPA) therapy who suddenly developed clinically relevant thrombocytopenia
      and signs of hepatotoxicity. Reduction of the VPA dosage led to clinical and
      laboratory parameter improvement, while discontinuation of therapy was not
      necessary. The current practice of the management of VPA-induced side effects is
      discussed in view of the current recommendations from the literature.

PMID- 14685006
TI  - Isotopic renal function studies in severe hypothyroidism and after thyroid
      hormone replacement therapy.
AB  - AIM: To investigate the possible changes in the renal tubular function in severe
      short-term hypothyroidism using (99m)Tc-MAG(3) renography. METHODS: 27
      consecutive thyroidectomized patients (7 males and 20 females) aged 19-79 (mean
      53) years were included in the present study. (99m)Tc-MAG(3) renography was
      performed in all patients before and after thyroid hormone replacement therapy.
      In addition, (51)Cr-EDTA clearance and serum creatinine concentrations were
      determined. RESULTS: The serum creatinine concentrations were significantly
      increased in hypothyroidism as compared with the concentrations after thyroxine
      substitution (1.30 +/- 0.44 vs. 1.04 +/- 0.32 mg/dl, p < 0.05). According to the
      (51)Cr-EDTA clearance, the glomerular filtration rate was significantly lower in
      hypothyroidism than after treatment (61 +/- 18 vs. 75 +/- 23 ml/min). In
      contrast, we did not find any significant change in the renographic parameters
      for (99m)Tc-MAG(3) before and after treatment (total excreted activity 20 min
      after administration 51 +/- 12 vs. 54 +/- 14%; T(max) left:right 4.2 +/- 1.77 :
      3.91 +/- 1.06 min vs. 4.1 +/- 1.66 : 4.4 +/- 1.96 min). CONCLUSIONS: We did not
      find any influence of thyroid hormones on the outcome of (99m )Tc-MAG(3)
      renography. As (99m)Tc-MAG(3) reflects the tubular function, it seems that the
      renal hemodynamic changes in severe hypothyroidism mainly affect the glomerular
      function. In general, the glomerular filtration rate reduction seems to be
      reversible after hormone substitution therapy; however, care has to be taken in
      patients with renal insufficiency.

PMID- 14685005
TI  - Randomized trial of an inhibitor of formation of advanced glycation end products
      in diabetic nephropathy.
AB  - BACKGROUND/AIMS: Pimagedine inhibits the formation of advanced glycation end
      products and slows the progression of diabetic complications in experimental
      models. This study was undertaken to determine if pimagedine ameliorates
      nephropathy in type 1 (insulin-dependent) diabetes mellitus. METHODS: This was a
      randomized, double-masked, placebo-controlled study performed in 690 patients
      with type 1 diabetes mellitus, nephropathy, and retinopathy. The patients
      received twice daily dosing with placebo, pimagedine 150 mg, or pimagedine 300 mg
      for 2-4 years. The primary end point was the time to doubling of serum
      creatinine; the secondary end points included evaluations of proteinuria, kidney
      function, and retinopathy. RESULTS: Serum creatinine doubled in 26% (61/236) of
      the placebo-treated patients and in 20% (91/454) of those who received pimagedine
      (p = 0.099). The estimated glomerular filtration rate decreased more slowly in
      the pimagedine-treated patients with a 36-month decrease from baseline of 6.26
      ml/min/1.73 m(2) as compared with 9.80 ml/min/1.73 m(2) in the placebo-treated
      patients (p = 0.05), and pimagedine reduced the 24-hour total urinary
      proteinuria. (The mean reduction from baseline at month 36 was 732 mg/24 h at the
      low dose and 329 mg/24 h at the high dose as compared with 35 mg/24 h in the
      placebo group; p </= 0.001.) Fewer pimagedine-treated patients with baseline and
      end point evaluations (31/324; 10%) as compared with those receiving placebo
      (16%; 28/179) experienced a three-step or greater progression of the retinopathy
      (Early Treatment of Diabetic Retinopathy Study) score (p = 0.030). Three patients
      receiving high-dose pimagedine but none receiving low-dose treatment developed
      glomerulonephritis. CONCLUSIONS: While this study did not demonstrate a
      statistically significant beneficial effect of pimagedine on the progression of
      overt nephropathy resulting from type 1 diabetes, it is noteworthy in providing
      the first clinical proof of the concept that inhibiting advanced glycation end
      product formation can result in a clinically important attenuation of the serious
      complications of type 1 diabetes mellitus.

PMID- 14685008
TI  - Reversal of reserpine-induced orofacial dyskinesia and cognitive dysfunction by
      quercetin.
AB  - Tardive dyskinesia (TD) is a serious neurological syndrome associated with long
      term administration of neuroleptics to humans and experimental animals. The
      pathophysiology of this disabling and commonly irreversible movement disorder is
      still obscure. It may be caused by a loss of dopaminergic cells or may be due to
      free radicals as a product of high synaptic dopamine levels. Quercetin is a
      bioflavonoid with strong antioxidant properties. Repeated treatment with
      reserpine (1.0 mg/kg) on each other day for a period of 5 days (days 1, 3 and 5)
      significantly induced vacuous chewing movements (VCMs) and tongue protrusions
      (TPs) in rats. Chronic treatment with quercetin for a period of 4 weeks to
      reserpine-treated animals significantly and dose dependently (50 and 100 mg/kg)
      reduced the reserpine-induced VCMs and TPs. Reserpine-treated animals also showed
      poor retention of memory in elevated plus-maze task paradigm. Chronic quercetin
      administration significantly reversed reserpine-induced retention deficits.
      Biochemical analysis revealed that chronic reserpine treatment significantly
      induced lipid peroxidation and decreased the glutathione (GSH) levels in the
      brains of rats. Chronic reserpine-treated rats showed decreased levels of
      antioxidant defense enzymes, superoxide dismutase (SOD) and catalase. Chronic
      administration of quercetin dose dependently (50-100 mg/kg) and significantly
      reduced the lipid peroxidation and restored the decreased GSH levels by chronic
      reserpine treatment. It also significantly reversed the reserpine-induced
      decrease in brain SOD and catalase levels in rats. The results of the present
      study clearly indicated that quercetin has a protective role against reserpine
      induced orofacial dyskinesia and memory impairment. Consequently, the use of
      quercetin as a therapeutic agent for the treatment of TD should be considered.

PMID- 14685009
TI  - Effects of cariporide (HOE642) on myocardial infarct size and ventricular
      arrhythmias in a rat ischemia/reperfusion model: comparison with other drugs.
AB  - The effects of pretreatment with cariporide on myocardial infarction and
      ventricular arrhythmias in a rat model of ischemia/reperfusion were compared with
      those of nicorandil, propranolol, and nifedipine. Each drug was administered
      intravenously before coronary occlusion. Cariporide at 0.1, 0.3, and 1 mg/kg
      significantly reduced the infarct size (infarct mass/risk mass) from 28 +/- 4%
      (vehicle control value) to 9 +/- 3, 9 +/- 3, and 5 +/- 2%, respectively.
      Propranolol at 2.5 mg/kg also significantly reduced the infarct size to 11 +/-
      1%. Neither nicorandil nor nifedipine was effective when given at 0.1 mg/kg.
      Cariporide dose dependently decreased the number of ischemia-induced ventricular
      premature beats (VPB), incidence and duration of ventricular tachycardia, and the
      number of reperfusion-induced VPB. Nicorandil was effective against only VPB
      after reperfusion, and propranolol reduced only postischemic arrhythmias, but
      nifedipine had no effect on either type of arrhythmia. In summary, cariporide
      reduced the infarct size and dose dependently suppressed arrhythmias induced by
      ischemia/reperfusion in rats. In contrast, in the present rat model, the doses of
      the other three drugs used in this study did not show comparable effects.

PMID- 14685010
TI  - Cardioprotective effects of (2S,3R,4S)-N'-benzyl-N"-cyano-N-(3,4-dihydro-2
      dimethoxymethyl-3-hydroxy-2-methyl-6-nitro-2H-benzopyran-4-yl)-guanidine (KR
      31372) in rats and dogs.
AB  - The cardioprotective effects of (2S,3R,4S)-N'-benzyl- N"-cyano-N-(3,4-dihydro-2
      dimethoxymethyl-3-hydro- xy-2-methyl-6-nitro-2H-benzopyran-4-yl)-guanidine (KR
      31372) were evaluated against ischemic/reperfusion injury in isolated rat hearts
      in vitro and in anesthetized rats and dogs in vivo. In isolated perfused rat
      hearts subjected to a 30-min global ischemia/30-min reperfusion, KR-31372 (1-10
      microM) significantly improved severe contracture (end-diastolic pressure and
      time to contracture), markedly reduced reperfusion lactate dehydrogenase release,
      and enhanced the recovery of reperfusion contractile function (left ventricular
      developed pressure and double product) in a concentration-dependent manner
      compared with the vehicle-treated group. In anesthetized rats subjected to a 45
      min coronary occlusion and a 90-min reperfusion, intravenous KR-31372 dose
      dependently reduced infarct size from 58.6% to 48.5, 48.1 and 39.6% at 0.3, 1.0
      and 3.0 mg/kg, respectively (p < 0.05). In anesthetized beagle dogs that
      underwent a 1.5-hour occlusion followed by a 5-hour reperfusion, KR-31372 (2
      mg/kg, i.v.) markedly reduced infarct size from 57.0% in controls to 28.0% (p <
      0.05). The cardioprotective effects of KR-31372 on contractile function in
      globally ischemic rat hearts and on reperfusion injury in anesthetized rats were
      significantly reversed by pretreatment with selective adenosine triphosphate
      sensitive potassium (K(ATP)) channel blockers, sodium 5-hydroxydecanoate and
      glibenclamide. Taken together, these results indicate that KR-31372 possesses
      potent cardioprotective effects in rats and dogs and its effects may be mediated
      by activation of mitochondrial K(ATP) channels.

PMID- 14685011
TI  - Activities of Pt(II) and Ru(III) triazole-pyrimidine complexes against
      Trypanosoma cruzi and T. brucei brucei.
AB  - We studied the biological activity of three newly synthesized metal complexes of
      triazole-pyrimidine derivatives that were previously observed to inhibit in vitro
      growth of epimastigotes of Trypanosoma cruzi and procyclic forms of Trypanosoma
      brucei brucei. We analyzed the possible inhibitory effect of these compounds on
      the synthesis of DNA, RNA and protein, ultrastructure and excretion of
      metabolites by these parasites. RNA synthesis was inhibited by all three
      complexes assayed. These complexes also led to anomalies of the main organelles
      (e.g. nucleus, kinetoplast and mitochondria). In addition, these complexes may be
      capable of altering the excretion of metabolites by the parasites.

PMID- 14685012
TI  - Chronic methionine load-induced hyperhomocysteinemia enhances rat carotid
      responsiveness for angiotensin II.
AB  - The purpose of the present study was to investigate the effects of chronic
      methionine treatment on vascular smooth muscle contractility for angiotensin II
      (Ang II). Methionine at 0.1, 1 and 2 g/kg body weight was administered daily in
      the drinking water for 2, 4, 8 and 16 weeks. Rat carotid rings from control and
      treated animals were placed in an organ chamber containing Krebs solution.
      Concentration-response curves for Ang II and potassium chloride (KCl) were
      determined. Methionine-rich diet enhanced the plasmatic homocysteine
      concentration, and the magnitude of the contractile response to Ang II was
      increased in carotid rings from treated animals after 8 and 16 weeks. However,
      the treatment did not alter KCl-induced contraction. In another set of
      experiments, the rings were incubated with indomethacin and curves for Ang II
      were obtained. Exposure of the rings to indomethacin inhibited the enhancement in
      the contractile response to Ang II. The present findings show that chronic
      methionine treatment enhances homocysteine plasmatic concentration leading to an
      enhanced Ang-II-induced contraction, which appears to be related to the release
      of vasoconstrictor prostanoid(s).

PMID- 14685013
TI  - Assessment of bleeding propensity in non-human primates by combination of
      selective tissue factor/VIIa inhibition and aspirin compared to warfarin and
      aspirin treatment.
AB  - This study in non-human primates was designed to evaluate the bleeding propensity
      of a selective, small molecule inhibitor of tissue factor (TF)/VIIa in
      combination with acetylsalicylic acid (ASA) in comparison to the combination of
      ASA and warfarin. Bleeding time was increased by ASA but was not prolonged
      further by the addition of the TF/VIIa inhibitor, PHA-927, at doses that elevated
      the prothrombin time to 8-fold. In contrast, bleeding time was prolonged by
      warfarin alone and further exacerbated by the presence of ASA. Acute blood loss
      at the bleeding site, while not significantly increased by either warfarin or PHA
      927, was increased substantially in several individuals treated with a
      combination of warfarin and ASA but not by the combination of TF/VIIa inhibitor
      and ASA. These data predict that TF/VIIa inhibition, in the presence of chronic
      aspirin therapy in patients with cardiovascular risk factors, will be a safe
      therapy for thrombotic disorders.

PMID- 14685014
TI  - Gender-related differences in the pharmacodynamics of furosemide in rats.
AB  - The possibility of gender differences in the relationship between dose and
      efficacy of drugs has historically been limited. The aim of the present study was
      to evaluate the influence of sex on the pharmacodynamics of furosemide (FUR) in
      adult Wistar rats. Conventional renal clearance studies were performed in the
      absence and in the presence of a FUR dose necessary to produce identical urine
      excretion rates of FUR in both sexes. Fractional excretions of sodium, potassium,
      and water were similar in male and female rats in the absence of FUR.
      Natriuretic, kaliuretic, and diuretic responses to FUR, when expressed in
      fractional terms, were significantly increased in female rats. Diuretic,
      natriuretic, and kaliuretic efficiencies of FUR were also higher in female rats
      as compared with males. This might be explained by the lower abundance of the Na
      K-2Cl cotransporter observed in homogenates from the medullae of female kidneys
      as compared with male ones.

PMID- 14685015
TI  - Plasma levels of coenzyme Q10 in children with hyperthyroidism.
AB  - OBJECTIVES: In hyperthyroidism, increased oxygen consumption and free radical
      production in the stimulated respiratory chain leads to oxidative stress. Apart
      from its antioxidative function, coenzyme Q10 (CoQ10) is involved in electron
      transport in the respiratory chain. The aim of this study was to determine
      whether there is a correlation between an increased respiratory chain activity
      and the state of CoQ10 in children with hyperthyroidism. METHODS: The CoQ10
      plasma concentration was measured by high-performance liquid chromatography in 12
      children with hyperthyroidism before and after treatment. RESULTS: In the
      hyperthyroid state, the plasma level of CoQ10 was significantly decreased in
      comparison with the level in the euthyroid state. The correction of the
      hyperthyroid state resulted in a normalization of the CoQ10 level. CONCLUSION:
      Plasma CoQ10 deficiency appears to be related to the stimulated respiratory chain
      activity in children with hyperthyroidism.

PMID- 14685016
TI  - Serum total prostate-specific antigen assay in women with Cushing's disease or
      alcohol-dependent pseudo-Cushing's State.
AB  - BACKGROUND: The distinction between Cushing's disease (Cushing's syndrome
      dependent on adrenocorticotropic hormone (ACTH)-secreting tumors of pituitary
      origin) and pseudo-Cushing's states (Cushingoid features and hypercortisolism
      sometimes present in alcoholic, depressed or obese subjects) can present a
      diagnostic challenge in clinical endocrinology. Recently, the availability of a
      highly sensitive immunofluorometric assay for the measurement of total prostate
      specific antigen (PSA) provided the possibility to measure serum PSA levels in
      women. Interestingly, PSA gene expression and protein production has been found
      to be upregulated by steroid hormones, such as androgens, glucocorticoids,
      mineral corticoids and progestins. In fact, serum total PSA concentrations appear
      to be higher in female patients with Cushing's disease than in normal women. We
      wondered whether a similar phenomenon also occurs in pseudo-Cushing's state.
      METHODS: In order to answer this question, we compared the serum total PSA levels
      measured in 10 female subjects with alcohol-dependent pseudo-Cushing's state with
      those observed in 8 female patients with Cushing's disease and in 15 age-matched
      healthy women. Serum testosterone, ACTH and cortisol, and 24-hour urinary
      cortisol levels were measured; cortisol suppression after dexamethasone was also
      tested in all subjects. RESULTS: The basal serum levels of ACTH and cortisol were
      significantly lower in normal subjects than in patients with Cushing's disease or
      pseudo-Cushing's state; these latter groups showed similar basal hormonal values.
      Dexamethasone administration was unable to suppress serum cortisol levels in 5
      subjects with Cushing's disease and 6 subjects with pseudo-Cushing's state. Serum
      testosterone values in the group with Cushing's disease were higher than in the
      other groups. No differences were observed between pseudo-Cushing's and normal
      subjects. Serum total PSA levels were significantly higher in women with
      Cushing's disease than in subjects with pseudo-Cushing's state and normal
      controls; these latter groups showed similar PSA values. When serum total PSA and
      testosterone levels were considered together, a significant positive correlation
      was observed in the group with Cushing's disease, but not in the other groups.
      CONCLUSIONS: These data indicate that the steroid milieu responsible for the
      elevation in serum PSA in women with Cushing's disease is not present in subjects
      with alcohol-dependent pseudo-Cushing's state, suggesting the possible use of PSA
      as a marker of differentiation between these pathological conditions in women.

PMID- 14685017
TI  - Factors influencing the pre- and in-hospital management of acute stroke--data
      from a Greek tertiary care hospital.
AB  - In a prospective observational study, data on pre- and in-hospital management of
      acute stroke patients were collected from 100 consecutive patients admitted to
      the emergency room (ER) of Papageorgiou Hospital, a tertiary health care facility
      in Thessaloniki, Greece. Public emergency services were used by 58% of the
      patients, and 42% were brought by their relatives. 27% of the patients arrived
      within 1.5 h, 45% within 3 h, and 71% within 6 h from symptom onset. The median
      interval from ER arrival to examination by a board-certified neurologist was 20
      min (range 5-40 min). Time from ER arrival until brain CT scan ranged from 17 min
      to 28 h, with a median of 1.7 h. The majority (57%) of acute stroke patients
      reached hospital and received adequate diagnostic and treatment within 6 h, and
      approximately 30% even within 3 h from symptom onset. Thus, and in contrast to
      widespread perception, there is a time window for hyper-acute stroke treatment in
      Greek public hospitals. However, the fraction of patients eligible for acute
      treatment may be increased by shortening both the interval from symptom onset to
      hospital arrival, and also the door-to-CT interval.

PMID- 14685018
TI  - Diet and general health: dietary counselling.
AB  - Dietary guidelines are designed to maintain an adequate intake of nutrients and
      to protect against diet-related disease, particularly cardiovascular disease and
      obesity. Current population dietary guidelines advocate a reduction in total fat
      intake, particularly saturated fat intake, to 25-35% of the energy intake and an
      increased intake of carbohydrate to more than 55% of the dietary energy intake,
      which should mainly be derived from starch. There is a positive relationship
      between total sugar intake and the incidence of dental caries where dental
      hygiene is poor and exposure to fluoride is low. However, this relationship is
      stronger for frequency of consumption of sugary foods. The frequent consumption
      of acidic food and beverages should be also avoided as this can result in erosion
      of the tooth enamel. Risk of caries can be minimised by good oral hygiene,
      appropriate exposure to fluoride and by restricting the intake sugar containing
      snacks between meals to no more than four occasions per day. A need for
      randomized controlled trials to assess the effectiveness of dietary modification
      on oral health in adults is identified.

PMID- 14685019
TI  - Dental plaque as a biofilm: a pilot study of the effects of nutrients on plaque
      pH and dentin demineralization.
AB  - Direct or in situ methods (e.g., confocal microscopy, microsensors) are used to
      study non-oral biofilms for almost two decades, and they have recently been
      introduced in the research of dental plaque. We combined a pH microsensor
      technique and transversal microradiography (TMR) in a pilot study where the
      effects of nutrient availability on plaque acidogenicity and on the development
      of caries-like lesions were assessed. One volunteer accumulated dental plaque for
      7 days in 0.2-mm-wide and 0.8-mm-deep dentin grooves at four conditions: (1)
      saliva only, (2) 8 x 5 min/day dipping in 10% sucrose solution, (3) 7 x 5 min/day
      consumption of sweet cookies plus one meal/day, and (4) subject's regular diet.
      Plaque pH versus time and depth profiles in the grooves were recorded ex vivo
      before and after sugar challenge. 'Saliva' plaque responded to sugar with slow pH
      decrease--minimum pH 5.6-5.8 was reached after 30 min, while sugar dipping
      resulted in metabolically active plaque (minimum pH 5.3-5.5 within 4-8 min). TMR
      analysis revealed no demineralization after these two periods. Metabolically
      active plaque leading to distinct lesions resulted from frequent plaque exposure
      to diets rich in starch and carbohydrates (groups 3 and 4). These findings
      strengthen the view that the plaque acidogenicity does not necessarily reflect
      cariogenicity, and that retention of food components may account for increased
      cariogenicity at plaque retention sites in the mouth.

PMID- 14685020
TI  - Experts' opinions on the role of diet in caries prevention.
AB  - A questionnaire was sent to 54 experts in preventive dentistry in 23 European
      countries in order to make an inventory of existing national dietary guidelines
      for the prevention of dental caries. In addition, the experts were asked to give
      their personal opinion on several issues concerning the relationship between diet
      and dental caries. Forty-five experts from 20 countries returned the
      questionnaire. In 13 European countries dietary guidelines for caries prevention
      were available issued by a National (Dental) Association or a Government Body.
      All guidelines emphasised a reduction of the frequency of intakes of cariogenic
      foods. Two of them included a threshold level for the amount of sugar. When asked
      for their personal opinions, almost all experts mentioned reduction of frequency
      of 'cariogenic' intakes as the principal dietary messages for caries prevention.
      Four experts, however, explicitly mentioned that proper oral hygiene with
      fluoride toothpaste is more important. There was no agreement among the experts
      about a daily number of cariogenic intakes in between meals that can be regarded
      as safe, nor whether the message: 'Use products with sugar substitutes' should be
      part of the dietary guidelines for the prevention of dental caries. There was no
      agreement amongst experts on preventive dentistry in Europe on the contemporary
      validity of the paradigm: 'Sucrose is the arch criminal of dental caries.' Taking
      the variation in opinions into account and the fact that a balanced diet may lead
      to a moderate eating and snacking frequency, the authors propose that the
      emphasis on good versus bad foods for caries prevention should be replaced by an
      emphasis on good versus bad diets.

PMID- 14685021
TI  - Risk groups: nursing bottle caries/caries in the elderly.

PMID- 14685022
TI  - The role of diet in the aetiology of dental erosion.
AB  - Acids of intrinsic and extrinsic origin are thought to be the main etiologic
      factors for dental erosion. There is evidence that acidic foodstuffs and
      beverages play a role in the development of erosion. However, the pH of a dietary
      substance alone is not predictive of its potential to cause erosion as other
      factors modify the erosive process. These factors are chemical (pKa values,
      adhesion and chelating properties, calcium, phosphate and fluoride content),
      behavioural (eating and drinking habits, life style, excessive consumption of
      acids) and biological (flow rate, buffering capacity, composition of saliva,
      pellicle formation, tooth composition, dental and soft tissue anatomy). The
      interplay between erosion and abrasion (specially oral hygiene practices) may be
      the main driver leading to the clinical manifestation of this disorder.
      Recommendations for patients at risk for dental erosion such as reducing acid
      exposure by reducing the frequency and contact of acids will be discussed.

PMID- 14685023
TI  - Left costocervical vein malformation with anomalous ramification of aortic arch
      in a dog.
AB  - This report describes coexistence of anomalous branches of the aortic arch and
      the costocervical vein malformation in a German shepherd dog. The first branch of
      the aortic arch was a bicarotid trunk that divided into the left and right common
      carotid arteries. The next branch to leave the aortic arch was a common trunk for
      the right and left subclavian arteries, a bisubclavian trunk, which was
      immediately bifurcated. The right subclavian artery passed over the esophagus
      forming a deep groove, so-called incomplete vascular ring on the dorsal wall of
      the esophagus. Although the esophagus was constricted by the right subclavian
      artery dorsally and by the trachea ventrally, no clinical symptoms of esophageal
      obstruction and dysphagia were observed. The left costocervical vein coursed
      caudoventrally, passed over the aortic arch, and entered the left ventricle. This
      vessel was much smaller than the right costocervical vein and was partially
      occluded at its origin.

PMID- 14685024
TI  - Glutamate and GABA concentrations in the cerebellum of novel ataxic mutant Pogo
      mice.
AB  - The Pogo mouse is an autosomal recessive ataxic mutant that arose spontaneously
      in the inbred KJR/MsKist strain derived originally from Korean wild mice. The
      ataxic phenotype is characterized by difficulty in maintaining posture and side
      to side stability, faulty coordination between limbs and trunk, and the
      consequent inability to walk straight. In the present study, the cerebellar
      concentrations of glutamate and GABA were analyzed, since glutamate is a most
      prevalent excitatory neurotransmitter whereas gamma-aminobutyric acid (GABA) is
      one of the most abundant inhibitory neurotransmitters, which may be the main
      neurotransmitters related with the ataxia and epilepsy. The concentration of
      glutamate of cerebellum decreased significantly in ataxic mutant Pogo mouse
      compared to those of control mouse. However, GABA concentration was not decrease.
      These results suggested that the decrease in glutamate concentration may
      contribute to ataxia in mutant Pogo mouse.

PMID- 14685025
TI  - Identification and epidemiological characterization of Streptococcus uberis
      isolated from bovine mastitis using conventional and molecular methods.
AB  - In the present study 130 S. uberis strains and one S. parauberis strain isolated
      from bovine milk samples of 58 different farms of various locations in Hesse,
      Germany, as well as two reference strains of each species were comparatively
      investigated for cultural, biochemical, serological and molecular properties. All
      S. uberis strains produced the enzyme beta-D-glucuronidase, while the S.
      parauberis strains were negative. The S. uberis and S. parauberis 16S rRNA genes
      were amplified by polymerase chain reaction and subsequently digested with the
      restriction enzymes RsaI and AvaII yielding species-specific restriction
      patterns. Both species were additionally identified by amplifying species
      specific parts of the genes encoding the 16S rRNA, the 23S rRNA and the 16S-23S
      rDNA intergenic spacer region, respectively. The CAMP factor gene cfu, a
      potential virulence factor of S. uberis, was amplified, corresponding to a
      phenotypically positive CAMP-reaction, using cfu-specific oligonucleotide
      primers. In addition the streptokinase/plasminogen activator encoding genes
      skc/pauA, a second potential virulence factor, could be amplified for 126 of the
      130 S. uberis but not for S. parauberis. A DNA fingerprinting of S. uberis
      strains, performed by macrorestriction analysis of their chromosomal DNA by
      pulsed-field gel electrophoresis, revealed that most of the isolates were not
      related to each other. However, identical DNA patterns were noted for some of the
      isolates within different quarters of an individual cow and also for different
      cows within the same farm. The generally unrelated DNA patterns indicated that S.
      uberis is a pathogen with multiple environmental habitats and that infections are
      caused by a great variety of strains.

PMID- 14685026
TI  - Expression of apxIA of Actinobacillus pleuropneumoniae in Saccharomyces
      cerevisiae.
AB  - Actinobacillus pleuropneumoniae is an important primary pathogen in pigs, in
      which it causes a highly contagious pleuropneumoniae. In our previous study,
      apxIA gene amplified from A. pleuropneumoniae Korean isolate by PCR with primer
      designed based on the N- and C-terminal of the toxin was cloned in TA cloning
      vector and sequenced. The nucleotide sequences of apxIA gene was reported to
      GenBank with the accession numbers of AF363361. Identity of the Apx IA from the
      cloned gene in E. coli was proved by SDS-PAGE and Western blot. Yeast has been
      demonstrated to be an excellent host for the expression of recombinant proteins
      with uses in diagnostics, therapeutics and vaccine productions. Therefore, to use
      the yeast as a delivery system in new oral subunit vaccine, apxIA gene was
      subcloned into Saccharomyces cerevisiae, and identified the expression of Apx IA
      protein. First, apxIA gene was amplified by PCR with the primers containing BamHI
      and SalI site at each end. Second, the DNA digested with BamHI and SalI was
      ligated into YEpGPD-TER vector, and transformed into S. cerevisiae 2805. Third,
      after identification of the correctly oriented clone, the 120-kDa of Apx IA
      protein expressed in S. cerevisiae 2805 was identified by SDS-PAGE and Western
      blot.

PMID- 14685027
TI  - Altered maturation of dendritic cells by taxol, an anticancer drug.
AB  - Taxol is a clinically useful anticancer drug against a variety of cancers.
      Although it has been known that taxol induces the apoptosis of cancer cells
      through cytochrome C release and the activation of caspases, the effect of taxol
      on dendritic cells (DCs) has not been studied. In this study, taxol enhanced the
      expression of MHC class II on DCs, compared to medium-treated immature DCs.
      Surprisingly, the viability of DCs was not decreased by taxol, whereas that of
      cancer cells was. It was confirmed that taxol did not induce the apoptosis of DCs
      based on annexin V-FITC/propidium iodide (PI) staining assay. Since previous
      study demonstrated that taxol induced the production of nitric oxide (NO) related
      to the viability of DCs, the level of NO from taxol-treated DCs was determined.
      Any significant amount of NO was not detected. Although taxol enhanced the
      expression of a maturation marker, MHC class II molecules, it strikingly
      inhibited the proliferation of splenic T lymphocytes activated by DCs. Taken
      together, this study demonstrated that taxol induced an altered maturation of
      DCs, the increase of MHC class II molecule but the inhibition of proliferation of
      splenic T lymphocytes. It is suggested that taxol may induce the
      immunosuppression in patients with cancer by the inhibition of DC-activated T
      cell proliferation, but not by the direct killing of DCs.

PMID- 14685028
TI  - Levels of lead in mineral salt commercial mixtures for beef cattle.
AB  - Lead concentrations was measured in samples of mineral mixtures used in beef
      cattle feed in the states of Sao Paulo, Parana, Mato Grosso and Mato Grosso do
      Sul, Brazil. Lead content was determined by inductively coupled plasma atomic
      emission spectrometry. Of the 60 analyzed samples, 21 had values greater than 30
      ppm (range less 1.6 to 460 ppm), which is the maximum concentration recommended.
      These findings show the necessity for careful industrial monitoring because some
      mineral mixtures contain sufficient lead to cause toxicity in animals.

PMID- 14685029
TI  - Phenotype of peroxisome proliferator-activated receptor-alpha(PPARalpha)deficient
      mice on mixed background fed high fat diet.
AB  - Considerable controversy exists in determining the role of peroxisome
      proliferator-activated receptor-alpha PPARalpha) on obesity. Previous reports
      demonstrated that PPARalpha is a critical modulator of lipid homeostasis, but the
      overt, obese phenotypic characterization in the strain of PPAR deficient
      (PPARalpha-/-) mice is influenced by other factors, including diet and genetics.
      Therefore, it is necessary to establish the phenotypic characterization of
      PPARalpha-/- mice prior to the obesity-related study. In this study, we observed
      phenotype of PPARalpha-/- mice on mixed genetic background (C57BL/6Nx129/Sv) fed
      a high fat diet for 16 weeks. PPARalpha-/- mice, regardless of sex, raised body
      growth rate significantly comparing with wild type and showed male-specific fatty
      change in the liver. They were shown to lack hepatic induction of PPARalpha
      target genes encoding enzymes for fatty acid beta-oxidation.

PMID- 14685030
TI  - Effects of cyclosporin A treatment on the pathogenesis of avian leukosis virus
      subgroup J infection in broiler chickens with Marek's disease virus exposure.
AB  - In this study, we investigated the effects of T-cell suppression on the
      pathogenesis of subgroup J avian leukosis virus (ALV-J). Chickens were treated
      with cyclosporin A (CSP) 50 mg/Kg body weight or a corresponding volume of olive
      oil per every three days after hatching until the end of experiment. Some of the
      chickens from each treatment group were infected with an isolate of ALV-J, ADOL
      7501, at 2 weeks of age. The effects of viral infection were compared to
      uninfected birds in same treatment group. Intramuscular injection of CSP induced
      significant T-cell specific immunosuppression determined by decreased cutaneous
      basophilic hypersensitivity response and decreased lymphocyte mitogenic activity
      using concanavalin A. Most of the chickens examined had Marek's disease virus
      infection prior to 3 weeks of age. The percentage of antibody-positive birds and
      antibody titers were similar in infected chickens between both treatment groups.
      The ratio of viremic chickens was significantly higher in CSP treated group than
      that of the Oil treated group. Microscopically, one CSP treated chicken had a
      nephroblastoma at 10 weeks post infection. At 7 and 10 weeks post-infection, more
      chickens had myeloid cell infiltrations in multiple organs including heart, liver
      and occasionally lung. Expression of ALV-J viral antigen determined by
      immunohistochemical staining was significantly higher in CSP treated chickens
      than Oil treated chickens at 10 weeks post-infection. This study indicated that
      chemically-induced T-cell suppression may enhance pathogenicity of the AVL-J
      virus in broilers.

PMID- 14685032
TI  - Analgesic effect of caudal epidural ketamine in cattle.
AB  - This study was performed to clarify the analgesic effect of ketamine injected
      into the first intercoccygeal (Co1-Co2) epidural space in standing cattle. Five
      adult cows were randomly received 3 treatments at least 1 week interval: 5, 10
      and 20 mL of 5% ketamine. Sedation, analgesia, ataxia and other effects on
      cardiopulmonary and rumen functions were assessed before ketamine administration
      and until 120 min. The analgesia without sedation was shown at tail and perineum
      about 5 min after all three treatments. The duration of analgesia was
      significantly increased according to the volume of ketamine (p<0.01). There was a
      similar tendency of ataxia with individual variation. There were minimal effects
      on cardiopulmonary and rumen functions. The present study showed that caudal
      epidural ketamine administration induced analgesia without sedation in cows, and
      the duration of analgesia was dose dependent with ataxia. However, the duration
      of analgesia after 5 and 10 mL ketamine administration is short for common
      surgical procedures and pain relief of perineum. Further studies are needed to
      prolong the duration of analgesia without side effects.

PMID- 14685031
TI  - Differences in the serum immunoglobulin concentrations between dairy and beef
      calves from birth to 14 days of age.
AB  - The changes in serum levels of immunoglobulins G, M and A of dairy and beef
      calves of well-managed herds were monitored from birth to 14 days post partum
      using single radial immunodiffusion. Serum levels of all three immunoglobulin
      classes reached its peak at 24 hours in both groups of calves after birth, at
      which time there were very high levels of each immunoglobulin present. The mean
      IgM and IgA levels of the two groups became same at 6 days and 8 days of age,
      respectively but the mean IgG level of beef calves was approximately twice that
      of dairy calves throughout the experiment.

PMID- 14685033
TI  - Ultrasonographic measurement of optic nerve sheath diameter in normal dogs.
AB  - This study was carried out to assess the feasibility of ultrasonographic
      measurements of the optic nerve sheath diameter (ONSD) in normal dogs and
      evaluate the effect of breed, sex, body weight and age on biometry of ONSD. The
      ONSDs were evaluated in 15 dogs (10-50 months old) with normal eye (7 Yorkshire
      terrier and 8 Maltese). Ultrasonographic measurements of the ONSD were carried
      out at a constant position located 5 mm behind the optic disc. Eyes were
      collected immediately after euthanasia, and were used for saline immersion
      technique and direct measurement by calipers for biometry of ONSD. In this study,
      there was no significant difference of ONSD between the left and the right eyes,
      and was no significant difference among ONSD values obtained from
      ultrasonographical method, saline immersion technique and direct measurement
      (k=0.95). Also, there was no correlations between ONSD and sex, body weight and
      age, but was significant between the mean ONSD of Yorkshire terrier and Maltese
      (p<0.01). The mean ONSD of Yorkshire terrier was 2.10 +/- 0.22 mm and Maltese was
      1.63 +/- 0.23 mm. This study suggests that ultrasonographic measurements is
      useful method for biometry of the ONSD in normal dogs and provides baseline
      information for the study of evaluating ONSD in various breeds and diagnosing
      several diseases with the change of the ONSD.

PMID- 14685034
TI  - Identification of a putative cellular receptor 150 kDa polypeptide for porcine
      epidemic diarrhea virus in porcine enterocytes.
AB  - Porcine epidemic diarrhea virus (PEDV) causes an acute enteritis in pigs of all
      ages, often fatality for neonates. PEDV occupies an intermediate position between
      two well characterized members of the coronavirus group I, human coronavirus
      (HCoV-229E)and transmissible gastroenteritis virus (TGEV) which uses
      aminopeptidase N (APN), a 150 kDa protein, as their receptors. However, the
      receptor of the PEDV has not been identified yet. A virus overlay protein binding
      assay (VOPBA) was used to identify PEDV binding protein in permissive cells. The
      binding ability of PEDV to porcine APN (pAPN) and the effects of pAPN on
      infectivity of PEDV in Vero cells were also investigated. VOPBA identified a 150
      kDa protein, as a putative PEDV receptor in enterocytes and swine testicle (ST)
      cells. Further the PEDV binding to pAPN was blocked by anti-pAPN and pAPN
      enhanced PEDV infectivity in Vero cells. In conclusion, these results suggested
      that pAPN may act as a receptor of PEDV.

PMID- 14685035
TI  - [Effect of H1 histamine receptor antagonists on T cell functions].

PMID- 14685036
TI  - [Early treatment for pollinosis].

PMID- 14685037
TI  - [Esophageal candidiasis as complication of inhaled steroid therapy].
AB  - Gastrointestinal endoscopy was performed in two bronchial asthma patients using
      inhaled corticosteroid who complained of odynophagia. The endoscopic finding was
      high grade with white moss (Grade III) in both patients. Esophageal candidiasis
      is often recognized in bronchial asthmatic patients receiving long-term
      fluticasone propionate (FP) dry powder (Diskhaler) inhalation. We therefore
      examined the complicated context of esophageal candidiasis in patients with long
      term FP inhalation. Out of 20 bronchial asthmatic patients who had been using FP
      inhalation long-term, seven showed signs of esophageal candidiasis. Three
      patients had mild grade (Grade I), one middle grade (Grade II) and three high
      grade (Grade III) candidiasis, with a frequency of 35%. This rate is higher than
      the usual spontaneous occurrence rate of esophageal candidiasis, and it is
      suggested that inhalation of corticosteroid medication can penetrate into the
      esophagus after deep inhalation. We tested this hypothesis in two studies. 1) To
      measure the esophageal concentration of FP, four healthy adults inhaled 200
      microg FP once. Right after inhalation, FP concentration in the esophageal
      washing fluid was 3.3 microg. On another day, 30 minutes after the same dose of
      inhaled FP, one FP concentration in the esophageal washing fluid was 0.67 microg
      (immediately laydown), and another was 0.11 microg (remained standing). This
      indicates that even though FP dissipates quickly, it remains in the esophagus 30
      minutes after inhalation. 2) We observed the process in one patient with high
      grade (Grade III) esophageal candidiasis. The time of inhalation was changed from
      just after getting up and just before going to bed to before breakfast and before
      dinner. Under this regimen, the signs of esophageal candidiasis improved from
      high to middle grade. CONCLUSION: If asthmatic patients do not go to sleep
      immediately after FP inhalation, the remaining FP in the esophagus decreases
      rapidly, thereby decreasing the risk of esophageal candidiasis. In addition, by
      changing the FP inhalation times to before breakfast and dinner, the remaining FP
      in the esophagus is washed away and does not remain in the esophagus. Therefore,
      this study, which avoided inhalation before going to bed, provides useful
      information for the prevention and improvement of esophageal candidiasis.

PMID- 14685038
TI  - [The effect of suplatast tosilate on the patients with atopic dermatitis-
      relationship between clinical symptoms and immunological parameters].
AB  - The Th2 cytokine inhibitor, suplatast tosilate (300 mg/day) was administered to
      45 cases of patients with atopic dermatitis for 8 weeks. The clinical scores,
      peripheral blood eosinophil counts, serum LDH levels, total IgE levels, serum
      eosinophil cationic protein (ECP) levels, and serum IL-5 levels before and after
      the treatment were observed and comparatively evaluated. The results of this
      study were summarized as follows. 1) Temporary improvements were found in the
      severity score, itching score, and sleeplessness score. All evaluated scores
      decreased significantly for all observation periods at 2, 4, 6 and 8 weeks after
      administration of suplatast tosilate compared with those before the
      administration. 2) In severe group, there was a significant improvement of
      severity score of lower limb. In moderate group there were significant
      improvements of severity score of head, face, neck and of upper limb. There were
      significant improvements of severity score of trunk and upper limbs in mild
      group. 3) The peripheral blood eosinophil counts and serum LDH levels
      significantly diminished compared with those before administration, but no
      significant difference was found in total IgE levels and serum ECP levels. 4) The
      serum IL-5 levels decreased after administration, however, there was no
      statistical significance. 5) The positive correlations between delta-severity
      score and delta-peripheral eosinophil count, delta-serum LDH levels, delta-serum
      ECP levels were found. 6) The positive correlations between delta-peripheral
      eosinophil count and delta-serum LDH levels, delta-serum ECP levels were
      observed. 7) There was no sign of adverse effects of the drug. From the above
      mentioned results, we confirmed the high efficacy of suplatast tosilate in the
      treatment of atopic dermatitis.

PMID- 14685039
TI  - [Natural killer cell activity among patients with atopic dermatitis].
AB  - We examined natural killer (NK) activity in 128 patients with atopic dermatitis
      (AD) to investigate the relationships between NK activity and severity of
      dermatitis, duration of disease, and mental states. The results showed the
      following: 1) No relationship was shown between severity of dermatitis and NK
      activity, neither between NK activity nor eosinophilic counts nor serum IgE. 2)
      Patients with longer duration of AD lesions showed significantly lower NK
      activity (P=0.036). The significant relationship was recognized between severity
      of dermatitis and the duration of disease (P=0.014). 3) No relationships were
      recognized between NK activity and mental states evaluated using the Profile Of
      Mood States (POMS) questionnaire, as tension-anxiety, depression-dejection, anger
      hostility, vigor, fatigue and confusion. From a psychoneuroimmunological
      viewpoint, chronic stress as having AD might influence the lower NK activity of
      patients with longer duration of AD.

PMID- 14685041
TI  - [The 3 effective cases of cough variant asthma with ramatroban].

PMID- 14685042
TI  - [Laryngeal allergy].

PMID- 14685040
TI  - [Immunotherapy by Japanese cedarpollen in atpic dermatitis].
AB  - Atopic dermatitis positive to Japanese cedar pollen showed the recurrence or
      worsening of the symptoms during the pollen season. In 22 cases, 6 children
      (mean, 11.4 y) and 16 adults (29.5 y) who showed positive to Japanese cedar
      pollen by RAST, CAST analysis were done by Cry j 1 0.01 approximately 10 micro
      g/ml and they showed the significant higher simulation indices compared to
      controls (P<0.01). Randomized analysis of the hyposensitized patients (10 cases)
      and non-hyposensitized (12 cases) showed significant lower stimulation indices in
      hyposensitized patients (P<0.01). In six cases stimulation indices were compared
      after one year of hyposensitization therapy. Four cases to whom hyposensitization
      were newly introduced showed the significant decreases of stimulation indices:
      19.83+/-4.97 (mean+/-SEM) to 6.84+/-6.36 (65.0%) by Cry j 1 0.01 microg/ml,
      19.73+/-5.65 to 6.85+/-1.78 (65.3%) by 0.1, 17.88+/-5.11 to 6.36+/-1.53 (64.4%)
      by 1, and 20.03+/-5.29 to 6.11+/-1.39 (69.5%) by 10, and they showed the
      significant decreases (P<0.05). By anti-IgE it decreased significantly from
      35.08+/-3.42 to 7.00+/-1.77 (79.7%) (P<0.01). In two cases who got
      hyposensitization therapy for 2 years and 1 1/2 years each, there were no
      significant decreases of stimulation indices. The symptoms improved significantly
      and there were little or no recurrence of the symptoms. Symptom scores (Rajka &
      Langeland) showed significant decreases. Thus, hyposensitization by cedar pollen
      in atopic dermatitis is a promising treatment.

PMID- 14685043
TI  - [Clinical significance and treatment of food allergy in children].

PMID- 14685044
TI  - [Development of nasal dosage form of oxatomide for rhinitis].
AB  - The possibility of oxatomide as the nasal dosage drug for the therapy of nasal
      allergy was studied. Oxatomide was well absorbed from the nasal cavity,
      indicating a high permeability to nasal epithelial layer after nasal
      administration. Acidic pH condition further enhanced the permeation of oxatomide
      across Caco-2 monolayers, due to the high solubility at the low pH range. Nasal
      dosage forms for oxatomide (dextrin form, hydroxypropyl-gamma-cyclodextrin form
      and the suspension of polyethylene glycol) was, therefore, adjusted to pH 5.0.
      This pH allowed a high solubility of oxatomide without the irritation to nasal
      epithelium. The effect of nasal administration of oxatomide was studied on
      experimental allergic rhinitis in sensitized guinea pig. All dosage forms of
      oxatomide significantly inhibited the dye leakage into the nasal cavity, and
      among three forms, dextrin form showed the highest effect. High viscosity of
      dextrin solution was considered to stabilize the dispersion of oxatomide and
      enhance the retention in the nasal cavity. These results suggest that oxatomide
      should be useful as nasal dosage drug for allergic rhinitis.

PMID- 14685045
TI  - [Research on infants with atopic dermatitis caused by food allergies].
AB  - We have examined 370 infants less than 12 months of age with atopic dermatitis
      about food allergies, especially by egg white antigens. Since the results of the
      skin scratch test and serum specific IgE antibody test often correspond to each
      other, only the serum specific IgE antibody test was given to infants over 6
      months of age. An oral provocation test using boiled egg white was given to 176
      patients, and 52 of them showed immediate positive reaction. The number of
      patients with a positive reaction was much fewer than expected. This may be due
      to lowered levels of egg white antigens from being boiled, and the majority of
      patients that took the test were over 12 months of age. Those infants with atopic
      dermatitis often react positively to both serum specific IgE antibody tests and
      skin scratch tests, therefore follow up studies on changes in the level of serum
      IgE antibody and reaction to oral provocation tests with infants over 6 or 7
      months of age must be done to determine if egg whites need to be eliminated from
      their diet or not.

PMID- 14685046
TI  - [The national survey of immediate type of food allergy].
AB  - BACKGROUND: The actual conditions regarding immediate type food allergy have not
      been fully understood. Appropriate countermeasures have not been taken so far.
      The objective of our research is to identify the actual conditions of immediate
      type food allergy in Japan for the purpose of contributing to future practices.
      SUBJECT: We conducted a survey on the patients in collaboration with 2689
      domestic hospitals which have pediatrics and more than 100 beds. We focused on
      these cases who presented with symptoms of allergy within 60 minutes of the
      intake of any offending food. RESULT: 60.4% of collaborators returned the
      questionnaire. We investigated 1420 cases in 498 hospitals. Average age of cases
      was 6.7+/-13.1 (Mean+/-SD). Ages not more than 8 years-old comprised 80.1% of the
      whole population. The most common offending foods were eggs, milk products,
      wheat, buckwheat, fish and fruits. In addition, offending foods varied depending
      on age. The clinical symptoms appeared at 24.2 minutes+/-19.4 minutes (Mean+/-SD)
      after the intake of offending foods. The most common clinical symptom was
      observed on the skin and respiratory organs. CONCLUSION: Based on the results of
      this study, the Ministry of Health, Labor and Welfare amended the ministerial
      ordinance concerning the allergy food labeling system. Five major offending foods
      (eggs, milk, wheat, buckwheat, and peanuts) were designated as ingredients to be
      specified on the label.

PMID- 14685047
TI  - [Analysis of scratching behavior in a picryl chloride induced atopic dermatitis
      model in mice].
AB  - To elucidate the actual state of scratching behavior of NC mice noted when PiCl
      induced dermatitis occurs, the circadian rhythm in scratching behavior of this
      mouse model was examined, and the time when scratching behavior, which is useful
      to evaluate the severity of itch, occurs was assessed. A steroid drug
      (Prednisolone ointment), which has been confirmed to inhibit dermatitis from
      worsening, was used to examine whether or not, or how it inhibits scratching
      behavior in this mouse model. It became clear that scratching behavior increased
      during a period from the evening to the night in the animals which had not been
      sensitized (normal animals); compared with the day time, scratching behavior
      occurred more often in the nighttime. It also became clear that scratching
      behavior increased in the animals with PiCl-induced dermatitis increase in the
      frequency of induction of dermatitis, and Prednisolone ointment significantly
      inhibited scratching behavior in the animals in which dermatitis had been induced
      with PiCl six times. From these results, it can be said that scratching behavior
      increases in PiCl-induced mouse atopic dermatitis models correlatively with the
      increase in the frequency of induction of dermatitis, and steroid drugs decrease
      the frequency of the scratching behavior. In conclusion, it is strongly suggested
      that this mouse model is useful for development of therapeutic methods and novel
      medicinal drugs for atopic dermatitis.

PMID- 14685048
TI  - [A case of cashew nut allergy followed by almond allergy].

PMID- 14685049
TI  - Genetic diversity of HIV in Africa: impact on diagnosis, treatment, vaccine
      development and trials.

PMID- 14685050
TI  - HIV biological variability unveiled: frequent isolations and chimeric receptors
      reveal unprecedented variation of coreceptor use.
AB  - OBJECTIVE: To follow the evolution of coreceptor use in HIV-1-infected
      individuals with varying rates of disease progression. METHODS: The coreceptor
      use of 278 sequential HIV-1 isolates from 23 individuals was tested by infection
      of two human cell lines, U87.CD4 and GHOST(3), expressing CD4 and CCR1, CCR2b,
      CCR3, CCR5, CXCR4, CXCR6 or BOB. Differences in coreceptor use were further
      dissected by testing chimeric coreceptors constructed by exchanging successively
      larger parts of CCR5 for corresponding regions of CXCR4. RESULTS: Three patterns
      of coreceptor use were distinguished: no evolution, evolution to CXCR4 use, and
      fluctuation. No evolution with stable CCR5 use (R5 phenotype) was linked to slow
      progression over 8-10 years in four patients. CXCR4-using virus was present from
      the onset (five patients) or appeared during clinical progression in all other
      patients, while taking zidovudine or didanosine monotherapy. The fluctuating
      pattern of coreceptor use, defined as reappearance of virus with R5 phenotype,
      was observed in five patients and, interestingly, followed initiation of highly
      active antiretroviral therapy in three of these. Monotropic R5 or X4 viruses were
      more selective in chimeric receptor use than R5X4 or multitropic viruses. Most
      importantly, the efficiency of chimeric receptor use increased over time.
      CONCLUSION: The increase in efficiency of chimeric receptor use allows a new
      interpretation of evolution of HIV-1 coreceptor use. Evolution could be a
      continuous process that may lead to changes in the way a coreceptor is used, with
      the potential of profound alteration in signalling at that receptor.

PMID- 14685051
TI  - Molecular mapping of epitopes for interaction of HIV-1 as well as natural ligands
      with the chemokine receptors, CCR5 and CXCR4.
AB  - OBJECTIVE: Mapping coreceptor epitopes used by the prototypic R5 and X4 strains,
      HIV-1BaL and HIV-1IIIB, in comparison with epitopes involved in the activation
      and signaling induced by the natural ligands, RANTES and SDF-1beta. DESIGN:
      Receptor hybrids between CCR5 and CXCR4 were constructed. METHODS: Using single
      overlap and extension PCR, increasing portions of CCR5 were replaced with
      corresponding parts of CXCR4. Viral interaction with these constructs was
      monitored in infection experiments using stably transfected cell lines, and
      ligand-induced activation of cells transiently expressing the constructs was
      measured in terms of calcium fluxes. RESULTS: SDF-1beta required an essentially
      complete CXCR4, whereas RANTES demanded both the N terminus and the first two
      extracellular loops of CCR5. HIV-1 infection experiments emphasized the
      importance of the CCR5 N terminus for infection with HIV-1BaL, whereas HIV-1IIIB
      was less demanding in its use of CXCR4. CONCLUSION: This study, for the first
      time monitoring CCR5 and CXCR4 ligand activation and HIV-1 interaction
      concomitantly, indicates that ligands and virus use different receptor epitopes
      which, in turn, vary between the two receptors. One particular chimera (FC-4b),
      having its junctional region close to the conserved cysteine in ECL2, functioned
      as coreceptor for both HIV-1BaL and HIV-1IIIB, but was not activated with RANTES
      or SDF-1beta. The results provide a basis for tailoring drugs that block viral
      entry through the two major coreceptors without interfering with their
      physiological function.

PMID- 14685052
TI  - Influence of HLA-B57 on clinical presentation and viral control during acute HIV
      1 infection.
AB  - BACKGROUND: HLA-B57, as well as cytotoxic T-lymphocyte (CTL) responses restricted
      by this allele, have been strongly associated with long-term non-progressive
      chronic HIV-1 infection. However, their impact on viral replication during acute
      HIV-1 infection is not known. METHODS: Clinical and immunological parameters
      during acute and early HIV-1 infection in individuals expressing HLA-B57 were
      assessed. HIV-1-specific T-cell responses were determined by peptide-specific
      interferon-gamma production measured using Elispot assay and flow-based
      intracellular cytokine quantification. RESULTS: Individuals expressing HLA-B57
      presented significantly less frequently with symptomatic acute HIV-1 infection
      (4/116, 3.4%) than expected from the frequency of chronically infected
      individuals expressing this allele (43/446, 9.6%; P < 0.05). During acute
      infection, virus-specific CD8 T-cell responses were dominated by HLA-B57
      restricted responses, with significantly broader (P < 0.02) and stronger (P <
      0.03) responses restricted by HLA-B57 than restricted by all other co-expressed
      HLA class I alleles combined. Six out of nine individuals expressing HLA-B57
      controlled HIV-1 viremia in the absence of therapy at levels < 5000 copies/ml
      (median, 515 copies/ml) during up to 29 months following acute infection.
      CONCLUSION: These data demonstrate that host genetic factors can influence the
      clinical manifestations of acute HIV-1 infection and provide a functional link
      between HLA-B57 and viral immune control.

PMID- 14685053
TI  - Factors associated with clinical progression in HIV-2 infected-patients: the
      French ANRS cohort.
AB  - OBJECTIVES: To identify factors associated with clinical progression in HIV-2
      infected patients. DESIGN: French prospective cohort initiated in 1994. METHODS:
      Follow-up data are collected twice a year; viral load is assessed once a year by
      cellular viraemia, quantitative proviral DNA and plasma RNA. A Cox proportional
      hazards model was used for studying baseline factors associated with clinical
      progression. RESULTS: By December 2001, 217 patients had been enrolled. At
      inclusion, 80%, 6% and 14% were Centers for Disease Control and Prevention (CDC)
      group A, B and C, respectively. Median CD4 cell count was 436 x 10(6)/l. In the
      48% of positive specimens, the median plasma RNA titre was 3.0 log10 copies/ml.
      Mean follow-up of the 179 patients seen at least twice was 34.4 months. Of these
      13 died and nine progressed to group C. Ninety-three (52%) received
      antiretroviral therapy during a mean of 33 months, including a protease inhibitor
      in 48%. The probability of remaining AIDS-free was 97% and 95% at 1 and 3 years,
      respectively. Independent variables associated with clinical progression were age
      > or = 40 years [hazard ratio (HR), 11; 95% confidence interval (CI), 1.4-91.8; P
      = 0.03] and plasma RNA (HR, 2.5 per additional log10 copies/ml; 95% CI, 1.3-4.7,
      P < 0.01). Prior group B symptoms and CD4 cell count < 200 x 10(6)/l were
      associated with progression to AIDS. AIDS and plasma RNA were predictive of
      death. CONCLUSION: Considering the limited progression rate of HIV-2 infection,
      combined antiretroviral therapy should be discussed in patients with high plasma
      RNA titres, which threshold value remains to be defined. It is recommended in
      case of AIDS, CDC group B symptoms or CD4 cell count < 200 x 10(6)/l.

PMID- 14685055
TI  - Improved outcomes of HIV-1-infected adults with tuberculosis in the era of highly
      active antiretroviral therapy.
AB  - OBJECTIVES: To compare the survival and treatment responses to antiretroviral
      therapy between HIV-1-infected patients with active TB (TB patients) and without
      (non-TB patients) in the era of highly active antiretroviral therapy (HAART).
      DESIGN: 8-year prospective observational study at a university hospital. METHODS:
      A total of 125 (17.5%) TB patients (median CD4 cell count at TB diagnosis, 37 x
      10(6) cells/l) and 591 non-TB patients (CD4 cell count at enrolment, 79 x 10(6)
      cells/l) were prospectively observed between June 1994 and October 2002.
      Virologic and immunologic responses were assessed in 230 antiretroviral-naive non
      TB patients and 46 TB patients who concurrently initiated antituberculous therapy
      and HAART. The clinical outcome was evaluated by comparing incidence of new AIDS
      associated opportunistic illnesses (OIs) and survival of all TB and non-TB
      patients. RESULTS Among antiretroviral-naive patients, CD4 cell count increase
      (71 versus 64 x 10(6) cells/l, P = 0.70) and proportions of patients achieving
      undetectable plasma viral load [20 of 46 versus 107 of 230, relative risk (RR),
      0.93; 95% confidence interval (95% CI), 0.65-1.34; P = 0.71] at week 4 of HAART
      were similar between the 46 TB and 230 non-TB patients, as was the virologic
      failure during HAART (RR, 1.49; 95% CI, 0.92-2.41; P = 0.14). The risk for HIV
      progression to new OIs was also similar between the two groups (adjusted RR,
      1.16; 95% CI, 0.764-1.77). The adjusted hazard ratio for death of TB patients
      compared with non-TB patients was 1.18 (95% CI, 0.65-2.32) before HAART era and
      0.89 (95% CI, 0.57-1.69) in HAART era. CONCLUSIONS: Our data indicated that
      virologic, immunologic, and clinical responses to HAART and prognosis of HIV-1
      infected TB patients who were concurrently treated with antituberculous therapy
      and HAART were similar to those of non-TB patients.

PMID- 14685054
TI  - Dose-ranging, randomized, clinical trial of atazanavir with lamivudine and
      stavudine in antiretroviral-naive subjects: 48-week results.
AB  - OBJECTIVE: To compare the efficiency and safety of atazanavir and nelfinavir in
      antiretroviral-naive patients. DESIGN: Randomization to atazanavir 400 mg or 600
      mg once daily; nelfinavir 1250 mg twice a day, plus lamivudine and stavudine.
      METHODS: A blinded (to the atazanavir dose), 48-week trial in patients with HIV-1
      RNA > or = 2000 copies/ml, CD4 cell count > or = 100 x 10(6) cells/l. Primary end
      point: change in HIV-1 RNA from baseline at 48 weeks. Secondary end-point:
      subjects with HIV-1 RNA < 400, and < 50 copies/ml, CD4 cell count changes,
      adverse events. RESULTS: The 467 randomized subjects had comparable baseline
      characteristics across treatments. With atazanavir 400 mg, 600 mg and nelfinavir,
      respectively, mean changes in HIV-1 RNA (log10 copies/ml) from baseline to 48
      weeks were -2.51, -2.58, -2.31; HIV-1 RNA < 400 copies/ml [intent-to-treat
      population (ITT), non-completion = failure (NC = F)], 64%, 67%, 53%; HIV-1 RNA <
      50 copies/ml (ITT NC = F), 35%, 36%, 34%; mean CD4 cell count increased
      comparably at 48 weeks (234 x 10(6), 243 x 10(6), 211 x 10(6) cells/l). Adverse
      events were similar across treatments with the exception of diarrhea (more
      frequent with nelfinavir) and jaundice (more frequent with atazanavir). Mean
      changes from baseline to 48 weeks were: fasting low density lipoprotein
      cholesterol, +5.2%, +7.1% and +23.2% (at 56 weeks) and fasting triglycerides (48
      weeks), +7.2%, +7.6% and +49.5%, in the atazanavir 400 mg, 600 mg, and nelfinavir
      groups, respectively (P < 0.01, atazanavir versus nelfinavir). CONCLUSIONS:
      Atazanavir is a potent, safe, well tolerated, and effective once-daily protease
      inhibitor with low pill burden (two capsules/day). Lipid changes with atazanavir
      were significantly less than with nelfinavir, however, clinical significance of
      these finding in terms of decreased cardiovascular risk is unknown.

PMID- 14685056
TI  - TMC125 exerts similar initial antiviral potency as a five-drug, triple class
      antiretroviral regimen.
AB  - OBJECTIVE: TMC125, a next generation, non-nucleoside reverse transcriptase
      inhibitor (NNRTI), demonstrated a remarkable decline of plasma HIV-1 RNA during a
      phase IIa study. We compared the initial rate of decline of plasma HIV-1 RNA
      achieved by TMC125 monotherapy with that of a triple class, five-drug regimen,
      containing drugs from all three currently licensed classes (zidovudine,
      lamivudine, abacavir, indinavir and nevirapine). METHODS: The decline in plasma
      HIV-1 RNA of 12 HIV-1 infected, antiretroviral (ART) naive patients treated for 1
      week with TMC125 monotherapy was compared with that observed in the ERA study (n
      = 11). The plasma HIV-1 RNA elimination rate constant was calculated based on at
      least four plasma HIV-1 RNA measurements during the first week of treatment
      (first-order elimination) and compared using the Student's t test. RESULTS:
      Median ages were 23 and 38 years for TMC125 and ERA patients, respectively (P =
      0.001), median baseline plasma HIV-1 RNA levels were 4.2 and 4.8 log10 copies/ml
      (P = 0.001) and median baseline CD4 T-cell counts were 458 x 10(6) and 360 x
      10(6) cells/l (P = 0.08). The median plasma HIV-1 RNA elimination rate constant
      was 0.68/day in TMC125 treated patients, and 0.56/day in ERA participants (P =
      0.24). The median decline in plasma HIV-1 RNA after 7 days was 1.92 and 1.76
      log10 copies (P = 0.77) and the median increase of CD4 T cells was 119 x 10(6)
      and 60 x 10(6) cells/l, respectively (P = 0.29). CONCLUSION: Monotherapy with
      TMC125 in ART-naive, HIV-1-infected individuals resulted in a similar rate of
      decline of plasma HIV-1 RNA during 1 week of therapy as therapy with a five-drug
      regimen.

PMID- 14685057
TI  - Provider bias in the selection of non-nucleoside reverse transcriptase inhibitor
      and protease inhibitor-based highly active antiretroviral therapy and HIV
      treatment outcomes in observational studies.
AB  - OBJECTIVE: To compare the characteristics of patients prescribed non-nucleoside
      reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI), and
      evaluate treatment outcomes in a setting in which nevirapine has been
      preferentially recommended since 1998. METHODS: A population-based analysis of
      antiretroviral-naive adults who started highly active antiretroviral therapy
      (HAART) between 1 August 1996 and 31 July 2000, and who were followed until 31
      March 2002. We compared baseline characteristics, and evaluated virological
      responses and mortality. RESULTS: Overall, 439 patients (28.8%) started HAART
      with NNRTI (94.1% used nevirapine), 100 (6.6%) used a double PI, and 983 (64.6%)
      used a single PI-based regimen. Substantial differences were observed between the
      baseline clinical characteristics of these populations. In adjusted analyses, in
      comparison with single PI therapy, only the use of NNRTI was associated with more
      rapid HIV-RNA suppression [relative hazard (RH) 1.42; 95% confidence interval
      (CI) 1.22-1.65; P < 0.001]. A total of 204 deaths were identified in the study
      population [42 (9.6%) NNRTI; 11 (11%) double PI; 151 (15.4%) single PI,
      respectively]. In adjusted analysis, NNRTI (RH 1.01; 95% CI 0.71-1.45) and double
      PI-based HAART (RH 0.74; 95% CI 0.40-1.39) had similar mortality rates to the
      single PI reference category. CONCLUSION: NNRTI use was associated with more
      rapid virological suppression, whereas similar rates of rebound and mortality
      were found. Nevertheless, major baseline differences existed between patients
      prescribed the various initial regimens. As such, it is likely that similar
      selection factors may explain why our findings contrast with several non
      randomized studies showing worse clinical outcomes of patients prescribed
      nevirapine.

PMID- 14685058
TI  - Stable prevalence of genotypic drug resistance mutations but increase in non-B
      virus among patients with primary HIV-1 infection in France.
AB  - OBJECTIVE: To evaluate the frequency of drug-resistant HIV-1 viral strains from
      patients presenting with primary infection in 1999-2000 and to survey the
      molecular epidemiology of these viruses circulating in France. METHODS:
      Resistance mutations were detected by sequencing the reverse transcriptase and
      the protease genes in plasma samples from 249 individuals. Phylogenetic analysis
      was performed on the reverse transcriptase genes. RESULTS: Ten per cent of
      patients [26/249; 95% confidence interval (CI) 7-15%] presented with virus
      mutations associated with resistance to at least one antiretroviral drug. The
      distribution of the resistance mutations was as follows: to nucleoside reverse
      transcriptase inhibitors in 19 (8%; 95% CI 5-12%) and to non-nucleoside reverse
      transcriptase inhibitors in 10 (4%; 95% CI 2-7%). Primary resistance mutations to
      protease inhibitors were detected in 14 (6%; 95% CI 3-9%). Twelve patients (5%;
      95% CI 3-8%) presented with virus harbouring mutations associated with resistance
      to two or three classes of antiretroviral drugs. The median HIV RNA in plasma at
      enrollment was lower in patients with one or more drug resistance mutations than
      in patients with no mutations (5.05 log versus 5.47 log, P = 0.05). Phylogenetic
      analysis revealed that 19% (14-24%) of patients harboured HIV-1 non-B subtype
      strains; this proportion remained high when Caucasian patients only were
      considered (14%). CONCLUSION: This study, performed within the French network on
      HIV-1 primary infection survey, revealed no change in the frequency of resistant
      viral strains over time, but showed an increasing prevalence of non-B subtypes
      overall and among Caucasian individuals.

PMID- 14685059
TI  - Trends in HIV and sexual behaviour in a longitudinal study in a rural population
      in Tanzania, 1994-2000.
AB  - OBJECTIVE: To describe the trends in HIV transmission and sexual behaviour in a
      rural population in Africa. DESIGN: An open community cohort study with
      demographic surveillance and surveys of all consenting adults. METHODS: All
      residing adults aged 15-44 years who participated in surveys in 1994-1995, 1996
      1997 and 1999-2000 were tested for HIV infection and provided information on
      sexual behaviour. The district AIDS control programme was the only intervention.
      RESULT: The prevalence of HIV among adults aged 15-44 years increased gradually
      from 5.9% in 1994-1995 to 6.6% in 1996-1997 and 8.1% in 1999-2000. The incidence
      of HIV increased from 0.8 to 1.3 per 100 person-years during 1994-1997 and 1997
      2000, respectively. In spite of a modest increase in knowledge during the study
      period, most individuals continued to feel that they were not at risk of HIV, and
      sexual risk behaviour remained largely unchanged, except for a small increase in
      condom use. HIV transmission levels continued to be higher in the trading centre
      than in the nearby rural villages within this small geographical area, although
      differences became smaller over time. CONCLUSION: The gradual and continuing
      spread of HIV and the striking lack of change in sexual behaviour in this rural
      population suggest that the low-cost district intervention package does not
      appear to be adequate to stem the growth of the epidemic, and more intensive AIDS
      control efforts are needed.

PMID- 14685060
TI  - Higher risk behaviour and rates of sexually transmitted diseases in Mwanza
      compared to Uganda may help explain HIV prevention trial outcomes.
AB  - OBJECTIVE: To determine to what extent the higher impact of treatment for
      sexually transmitted diseases (STD) on HIV incidence in Mwanza, Tanzania than in
      Rakai and Masaka, Uganda might be explained by baseline differences between the
      trial populations. DESIGN: A re-analysis of baseline data from the three trial
      populations comparing demography, sexual risk behaviour and HIV/STD epidemiology.
      METHODS: Data were compared after age-standardization and adjustments for sample
      selection where necessary. STD rates were also adjusted for the sensitivities and
      specificities of the diagnostic techniques used. RESULTS: Demographic patterns
      were similar across populations, apart from effects of AIDS on fertility and
      mortality (including widowhood) in Uganda. Higher sexual risk behaviours,
      including younger age of sexual debut, higher numbers of recent partners and
      lower frequency of condom use, were apparent in Mwanza compared to Masaka and
      Rakai. High-titre serological syphilis, gonorrhoea, chlamydia infection and
      trichomoniasis were all more prevalent in Mwanza, except for chlamydia infection
      in males. There was little difference between sites in the seroprevalence of
      Herpes simplex virus type-2. Age patterns in the prevalence of short-duration STD
      and current risk behaviours were similar across sites but all-titre serological
      syphilis was more prevalent among older participants in Rakai and Masaka than
      Mwanza. CONCLUSIONS: Differences between trial populations included higher
      reported risk behaviour and higher rates of curable STD in Mwanza compared to
      Rakai and Masaka. These differences probably relate to previous reductions in
      risk behaviour in Uganda and may explain, at least in part, the contrasting
      results of these trials.

PMID- 14685061
TI  - Community randomized trials for HIV prevention: the past, a lesson for the
      future?

PMID- 14685062
TI  - Didanosine-ribavirin combination: synergistic combination in vitro, but high
      potential risk of toxicity in vivo.

PMID- 14685063
TI  - Response to Soriano et al., 'Treatment of chronic hepatitis C virus infection: we
      must target the virus or liver fibrosis?'.

PMID- 14685064
TI  - Drug resistance is uncommon in pregnant women with low viral loads taking
      zidovudine monotherapy to prevent perinatal HIV transmission.
AB  - Zidovudine monotherapy is used to reduce perinatal HIV transmission in women with
      low viral loads. There are few data on the risk of drug resistance in this select
      cohort of women. We determined the prevalence of newly acquired mutations
      conferring reduced sensitivity to zidovudine after exposure during pregnancy, and
      found that the development of mutations was uncommon and was restricted to women
      treated before 1998 who had higher baseline viral loads than those currently
      recommended monotherapy.

PMID- 14685065
TI  - Association of hormonal contraception and HIV-seroprevalence in Nairobi, Kenya.
AB  - Among women attending family planning clinics in Nairobi, Kenya, the HIV
      seroprevalence rates for different contraceptive methods were:
      depomedroxyprogesterone acetate (DMPA) 431/3279 (13.1%), combination oral
      contraceptive pill 114/1073 (10.6%), and progesterone-only contraceptive pill
      (POCP) 45/741 (6.1%). After adjusting for age, marital status, and parity, women
      using the POCP had a lower HIV seroprevalence (adjusted odds ratio 0.5, 95%
      confidence interval 0.3-0.7) than women using DMPA. This association was most
      pronounced among POCP users of lower parity.

PMID- 14685066
TI  - Pharmacokinetics of amprenavir given once or twice a day when combined with
      atazanavir in heavily pre-treated HIV-positive patients.
AB  - We studied the pharmacokinetics of amprenavir at doses of 600 mg twice a day or
      1200 mg once a day, when co-administered to HIV-positive patients with 400 mg a
      day of atazanavir without a ritonavir booster. Our preliminary results suggest
      that amprenavir and atazanavir could be coadministered and that amprenavir could
      be boosted by atazanavir without the need for ritonavir pharmaco-enhancement.

PMID- 14685067
TI  - Intrafamilial transmission of HIV-1.

PMID- 14685068
TI  - An open-label assessment of TMC 125--a new, next-generation NNRTI, for 7 days in
      HIV-1 infected individuals with NNRTI resistance.
AB  - The development of resistance to any of the currently licensed non-nucleoside
      reverse transcriptase inhibitors (NNRTI) invariably leads to cross-resistance to
      the drugs in that class. New NNRTI, that have the promise of being active even
      when such 'signature' mutations are present, are in development. Such novel
      therapies could be effective after current NNRTI failure as there would probably
      be no cross-resistance. We assessed the short-term efficacy and safety of a next
      generation NNRTI, TMC 125, a diarylpyrimidine derivative that has in vitro
      activity against NNRTI resistant HIV-1. TMC 125 was studied in HIV-1 infected
      patients with high-level phenotypic NNRTI resistance in an open-label phase IIa
      trial. METHODS: Sixteen individuals receiving an NNRTI-containing antiretroviral
      regimen (efavirenz or nevirapine) with an HIV-1 RNA viral load of > 2000
      copies/ml and phenotypic resistance to NNRTI, received TMC 125 for 7 days, as a
      substitute for their current NNRTI in their failing therapy. Full pharmacokinetic
      profiles were investigated. FINDINGS: The primary end point--viral load decay
      rate per day--was 0.13 log10 RNA copies/ml per day. Over 7 days, we observed a
      median 0.89 log10 decrease in HIV-1 viral load; seven individuals (44%) had a
      decrease of > 1 log10. The most significant adverse effects were grade I
      diarrhoea (31%) and a mild headache (25%). Steady-state drug levels were achieved
      by day 6. INTERPRETATION: TMC 125, a next generation NNRTI, is well tolerated and
      demonstrates significant and rapid antiviral activity in patients with high
      levels of phenotypic NNRTI resistance to current NNRTI.

PMID- 14685069
TI  - Treatment of pediatric gastroesophageal reflux disease: current knowledge and
      future research. Proceedings of a conference sponsored by the Children's
      Digestive Health and Nutrition Foundation in cooperation with the North American
      Society for Pediatric Gastroenterology, Hepatology and Nutrition. December 6-8,
      2000. Washington, DC, USA.

PMID- 14685070
TI  - Changing the paradigm: new directions in federal oversight of human research.
AB  - The system of institutional review boards (IRBs) was established about 30 years
      ago for the protection of human subjects and as a mechanism for assuring an
      independent peer review of research activities. To keep pace with an evolving
      environment, a new model for human research oversight is needed that focuses less
      on achieving regulatory compliance and more on applying our conscience to the
      responsible conduct of research. The recent implementation of a unified federal
      registration system for IRBs and a new assurance system point the way to a more
      effective structure for the oversight of clinical trials.

PMID- 14685071
TI  - Overview of pediatric gastroesophageal reflux disease and proton pump inhibitor
      therapy.
AB  - Symptoms of gastroesophageal reflux disease (GERD) are prevalent in children of
      all ages. Despite limited clinical data, proton pump inhibitors (PPIs) are
      frequently prescribed in pediatric patients. Studies are needed to determine the
      natural history of GERD, to assess its impact on the quality of life of affected
      children, and to identify risk groups in infancy and childhood. There is a
      critical need to evaluate PPI efficacy and safety in infants and children.

PMID- 14685073
TI  - The role of lower esophageal sphincter function and dysmotility in
      gastroesophageal reflux in premature infants and in the first year of life.
AB  - Transient relaxations of the lower esophageal sphincter (tLESRs), but not delayed
      gastric emptying, are major mechanisms of gastroesophageal reflux in premature
      infants. These findings are similar to those seen in older children and adults
      with gastroesophageal reflux disease. Newer antireflux therapies should be
      developed that target the reduction of gastric acidity or reduction in the number
      of tLESRs.

PMID- 14685072
TI  - Acid secretion from birth to adulthood.
AB  - All infants, including premature infants as young as 24 weeks' gestational age,
      are able to maintain an intragastric pH below 4 from the first day of life. By 24
      weeks, maximal acid output approaches that in adults. In adult studies, proton
      pump inhibitors (PPIs) are highly effective in relieving reflux symptoms and
      healing reflux esophagitis. Studies are needed to evaluate PPI efficacy and
      appropriate dosing in infants and children. Consequences such as
      hypergastrinemia, bacterial overgrowth, and other potential adverse events
      associated with long-term PPI use also warrant evaluation in the pediatric
      population.

PMID- 14685074
TI  - Eosinophilic esophagitis in children and adults.
AB  - Children with eosinophilic esophagitis, an isolated, severe esophageal
      eosinophilia, present with symptoms similar to gastroesophageal reflux but do not
      experience response to aggressive antireflux therapy. Increasingly, eosinophilic
      esophagitis is considered to be a separate entity from reflux disease. Current
      theory suggests that the former may be caused by cell-mediated food
      hypersensitivity or may be a subset of eosinophilic gastroenteritis. Reports
      support the efficacy of dietary restriction or corticosteroid therapy. Additional
      research is needed to determine etiology, allow earlier clinical recognition, and
      improve treatment.

PMID- 14685075
TI  - Tests to assess symptoms of gastroesophageal reflux in infants and children.
AB  - In studying antireflux medications, we may use tests for assessing symptoms of
      gastroesophageal reflux to establish or confirm a diagnosis of reflux disease and
      to evaluate whether study subjects are improving with therapy. Symptom assessment
      questionnaires need to be validated, results need to be reproducible, and the
      outcome variables measured need to be clinically relevant. Other outcomes for
      clinical trials include measures of esophagitis: histologic (morphometric)
      measures in infants and endoscopic and histologic visualization in older
      children. Intraesophageal pH monitoring studies may be useful for obtaining
      pharmacodynamic data.

PMID- 14685076
TI  - Outcomes of pediatric gastroesophageal reflux disease: in the first year of life,
      in childhood, and in adults...oh, and should we really leave Helicobacter pylori
      alone?
AB  - The prevalence of gastroesophageal reflux (GER) in childhood varies by age. As in
      adults, GER can result in a spectrum of disease manifestations. Children with
      gastroesophageal reflux disease (GERD) may become adults with GERD, as suggested
      by the frequency of childhood reflux symptoms reported by adults with reflux
      disease. Some studies suggest a causative association between Helicobacter pylori
      infection and GERD, whereas others postulate a protective role for H. pylori. To
      better understand pediatric GERD, age-appropriate case definitions and
      multicenter randomized controlled treatment trials are critically needed.

PMID- 14685077
TI  - Current regulatory policies regarding pediatric indications and exclusivity.
AB  - Pediatric studies have resulted in changes in the dose of many medications given
      to children and an increased awareness of safety issues. An additional 6 months
      of pediatric exclusivity legislated under the Food and Drug Administration (FDA)
      Modernization Act of 1997 for pediatric studies undertaken in response to written
      requests from the FDA have stimulated the conduct of a large number of studies.

PMID- 14685078
TI  - Efficacy and safety measurements of proton pump inhibitors in infants and
      children.
AB  - The design of studies to evaluate the efficacy of acid-lowering drugs in children
      differs significantly from study designs in adult populations. Efficacy
      measurements may be less extensive than those used in adult studies because of
      limitations that exist secondary to concerns for patient safety, parental and
      institutional review board acceptance of efficacy end points, and existing
      standards of care within the pediatric gastroenterology community. Study designs
      involving patients who would routinely receive acid-lowering therapy have been
      successfully used to characterize the pharmacokinetics and pharmacodynamics of
      acid-lowering therapies (H2 receptor antagonists) and have led to pediatric
      labeling for these drugs. This approach may likewise be used in the study of
      newer acid-lowering agents, such as proton pump inhibitors.

PMID- 14685079
TI  - Proton pump inhibitors in pediatrics: relevant pharmacokinetics and
      pharmacodynamics.
AB  - SUMMARY: A marked discordance between the disposition of proton pump inhibitors
      (PPIs) in plasma and the kinetics of effect suggests the need for new approaches
      to characterize the clinical pharmacology of PPIs in infants and children. An
      assessment of pharmacokinetics and pharmacodynamics must take into account the
      genetic polymorphism of CYP2C19 and the impact of ontogeny on the activity of
      this and other enzymes (e.g., CYP3A4) which affect the biotransformation of the
      PPIs and, thus, their plasma clearance. In addition, the potential effects of
      extemporaneous formulations of the drugs on their rate and extent of absorption
      must be considered. Because of the apparent safety of PPIs and a well
      demonstrated dose-response-effect relationship in adults, pediatric
      pharmacokinetic data and an exposure correlate, such as the dose-area-under-the
      plasma-concentration-versus-time-curve relationship, can be used as a bridge to
      determine pediatric dosing.

PMID- 14685080
TI  - Are proton pump inhibitors indicated for the treatment of gastroesophageal reflux
      in infants and children?
AB  - SUMMARY: Randomized controlled trials in the pediatric population that support
      the efficacy of proton pump inhibitors for the treatment of gastroesophageal
      reflux (GER) are lacking. Studies are needed to establish the safety of long-term
      acid suppression in infants and children, as well as to confirm a causal
      relationship between GER and extraesophageal symptoms and signs.

PMID- 14685081
TI  - Do children with gastroesophageal reflux become adults with gastroesophageal
      reflux? What is the role of Acid suppression in children?

PMID- 14685082
TI  - What safety data are needed for a medication to treat gastroesophageal reflux in
      premature infants? In children younger than 1 year of age? How to design a long
      term safety registry for children?

PMID- 14685083
TI  - What outcome measures are needed to assess gastroesophageal reflux disease in
      children? what study design is appropriate? what new knowledge is needed?

PMID- 14685084
TI  - Primary hyperparathyroidism.
AB  - PURPOSE OF REVIEW: This contribution presents research progress concerning
      primary hyperparathyroidism (pHPT), and the background for recent notable changes
      in treatment policy. RECENT FINDINGS: Research has clarified that most patients
      with pHPT require surgery due to risk for osteoporosis, renal stones, and
      possibly silent complications of renal impairment, cardiovascular disease, and
      common psychiatric disability. Genetic studies have advanced, but the cause of
      the disease remains unclear for most patients. Localization methods for
      parathyroid tumors have improved and increased the interest for less invasive
      operative methods with shorter hospital stays and reduced costs for the patient.
      It is important to delineate when this really will imply progress and to use the
      new diagnostic methods in discussions of appropriate treatment strategies. It has
      also become evident that older pHPT patients especially could benefit from
      medical treatment of bone mineral deficit, and they may also need vitamin D or
      vitamin D analogues to prevent progress of the disease. SUMMARY: pHPT is a common
      disorder among postmenopausal women, in whom most commonly applied surgical
      treatment has proven markedly efficient. There is now increased interest to
      better understand possible causes of the disease and schedule the most efficient
      surgical and medical treatment and discuss possible prophylaxis.

PMID- 14685086
TI  - Pheochromocytoma and functional paraganglioma.
AB  - PURPOSE: Pheochromocytomas and paragangliomas are rare tumors of chromaffin cell
      origin. Their identification is likely increasing owing to the increased use of
      radiographic images detecting incidental adrenal masses. RECENT FINDINGS: The
      pathophysiology of hypertension induced by the release of catecholamines and
      newly discovered peptides has been shown to be more complex than the concept of
      episodic catecholamine release. SUMMARY: This review looks at the most recent
      advances in the physiology and molecular basis of these tumors.

PMID- 14685087
TI  - Adrenocortical cancer: recent clinical and molecular advances.
AB  - PURPOSE OF REVIEW: Adrenocortical cancer (ACC) is an uncommon disorder that
      remains a challenge to the surgeon and oncologist. When the disease is localized
      to the adrenal gland and readily amenable to surgical resection, reasonable 5
      year survival rates are possible. Locally invasive disease carries a poorer
      prognosis, and metastatic disease is uniformly fatal within 1 year. In this
      review, we summarize the current knowledge regarding the clinical management of
      ACC and the molecular mechanisms underlying the disease. RECENT FINDINGS: The
      clinical manifestations, staging, and current treatment for ACC has been well
      documented. Surgery is still the mainstay of treatment, but identifying molecular
      targets for chemotherapeutic agents or monoclonal antibodies would be a great
      advance. At present, our understanding of pathogenic mechanisms is crude;
      however, the molecular events regulating this aggressive disease are beginning to
      emerge, especially in the last few years. The advent of laparoscopic
      adrenalectomy has also created its own dilemmas regarding the appropriate
      surgical approach to the large, potentially malignant adrenal mass. SUMMARY: The
      challenge in the management of this disease lies in understanding the molecular
      mechanisms that underlie the development of ACC with the diagnostic and
      therapeutic benefits that would ensue.

PMID- 14685088
TI  - Apoptosis in human cancer cells.
AB  - PURPOSE OF REVIEW: Apoptosis, or programmed cell death, is a vital physiologic
      process to eliminate damaged or unwanted cells. Defects in apoptosis promote
      tumor formation and make cancer cells resistant to therapy. This review provides
      an overview of recent advances in the understanding of apoptosis in human cancer
      cells. RECENT FINDINGS: Recent studies revealed that the apoptotic machinery in
      humans consists of a molecular network of a large number of proteins. These
      proteins regulate a cascade of events in signaling, commitment and execution
      stages of apoptosis through multiple parallel pathways. Delineation of the basic
      mechanisms of apoptosis has shed light on how apoptosis is deregulated in human
      cancer cells. Therapeutic strategies based on apoptosis have also been designed
      to selectively target tumor cells. SUMMARY: Understanding the basic mechanisms of
      apoptosis and determining how cancer cells evade apoptosis will afford
      discoveries of new molecular targets and better cancer therapies.

PMID- 14685089
TI  - Chromosomal instability.
AB  - PURPOSE OF REVIEW: This review discusses numerical and structural chromosomal
      instability in cancer cells and its possible etiologies, highlighting the recent
      literature. RECENT FINDINGS: Defects in chromosomal segregation, telomere
      stability, and the DNA damage response play significant roles in chromosomal
      instability in cancer. SUMMARY: The pace of discoveries into the biologic basis
      of chromosomal instability in cancer cells is quickening and the various causes,
      previously thought to be unrelated, are being found to be intertwined. Because
      chromosomal instability is likely to be a main mechanism behind tumor evasion of
      therapy, understanding the causes and their implications for diagnostic and
      prognostic evaluation and therapy is of tantamount importance.

PMID- 14685090
TI  - Recent advances in telomere biology: implications for human cancer.
AB  - PURPOSE OF REVIEW: Research into the basic biology of telomeres continues to
      reveal details relevant to fundamental aspects of human cancer. The goal of this
      review is to highlight discoveries made within the last year, with emphasis on
      their relevance to cancer prevention, diagnosis, prognostics, and treatment.
      RECENT FINDINGS: Increasing evidence indicates that dysfunctional telomeres
      likely play a causal role in the process of malignant transformation, in at least
      a fraction of human cancers, by initiating chromosomal instability. Telomeres
      form protective capping structures composed of telomeric DNA complexed with a
      multitude of associated proteins, the loss of which can have profound effects on
      telomeric stability. Critical telomeric shortening can lead to telomere
      "uncapping" and may occur at the earliest recognizable stages of malignant
      transformation in epithelial tissues. The widespread activation of the telomere
      synthesizing enzyme telomerase in human cancers not only confers unlimited
      replicative potential but also prevents intolerable levels of chromosomal
      instability. Several details regarding telomere structure and telomerase
      regulation have recently been elucidated, providing new targets for therapeutic
      exploitation. Various therapeutic strategies aimed at either telomerase or its
      telomeric substrate are showing promise and may synergize with established anti
      cancer agents. Further support for anti-telomerase approaches comes from recent
      studies indicating that telomerase may possess additional functions, beyond
      telomere maintenance, that support the growth and survival of tumor cells.
      SUMMARY: Substantial progress has been made in understanding the complex
      relationships that exist between telomeres and cancer. However, important issues,
      such as transient activation of telomerase in normal cells and the potential for
      tumor cell immortalization via telomerase independent means, remain to be
      clarified.

PMID- 14685091
TI  - Allelic variations in gene expression.
AB  - PURPOSE OF REVIEW: Genetic variants determine phenotypic variability. Many
      genetic studies suggest that protein structural variations predispose the
      population to more than 1000 different hereditary diseases. Unfortunately,
      despite the study of genetic polymorphisms for many decades, the milder
      phenotypic variations believed to account for most human physical and behavioral
      differences and underlying the most common human genetic diseases (including
      cancers) cannot be accounted for easily by these variations in the protein coding
      sequences. Thus, it has been hypothesized that the study of natural differential
      expression presenting within and among populations may enhance understanding of
      human phenotypic variation. RECENT FINDINGS: During the last year, reports
      identifying variations in gene expression in different organisms and finding
      subtle changes of gene expression associated with common genetic disease have
      pointed to variations in gene expression as playing a central role in molecular
      evolution and human disease. Advances in the functional analysis of gene
      regulatory networks-in particular, new methods for distinguishing cis-acting
      components from trans-acting factors-have provided the impetus for these
      discoveries. SUMMARY: This review represents current knowledge about allelic
      variation in gene expression and its increasingly important role in understanding
      the genotype-phenotype relation. Characterization of these allelic variations may
      open largely uncharted territory in genomics for biomedical researchers and may
      eventually lead to the discovery of the causative genes of common hereditary
      diseases and their mechanism of action.

PMID- 14685092
TI  - Tumor endothelial markers: new targets for cancer therapy.
AB  - PURPOSE OF REVIEW: Targeting the endothelial cells that line tumor infiltrating
      blood vessels is a new anticancer strategy that has gained widespread support
      from biologists and clinicians. Here we highlight different approaches currently
      being used to target tumor endothelium and discuss new avenues for intervention
      that have been opened through the recent identification of tumor endothelial
      markers (TEMs). RECENT FINDINGS: The ability of Avastin to prolong survival in a
      Phase III clinical trial of human colorectal cancer has established the validity
      of the anti-angiogenic approach. However, realization of the full potential of a
      vascular targeting strategy may require the exploitation of molecules which are
      highly restricted in expression to tumor endothelium. Here we explore the
      potential of TEMs as new targets for cancer therapy. Current knowledge of these
      markers and their relation to other family members in the context of tumor
      angiogenesis is discussed. In particular, we highlight those molecules which, by
      virtue of their structure, cell-surface location and expression pattern, appear
      to hold promise as targets for future drug development. The identification of
      TEM8 as the anthrax toxin receptor and the successful targeting of this receptor
      in preclinical tumor models make this molecule a particularly attractive
      candidate for future vascular targeting studies. SUMMARY: Technological advances
      in cellular fractionation and genomics enabled the identification of several
      markers preferentially expressed on human tumor endothelium. Studies of these
      TEMs are expected to aid in our understanding of angiogenesis and could lead to
      the development of new imaging and diagnostic agents for cancer.

PMID- 14685093
TI  - Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2
      diabetes: a new perspective for an old disease.
AB  - BACKGROUND: The Roux-en-Y gastric bypass and the biliopancreatic diversion
      effectively induce weight loss and long-term control of type 2 diabetes in
      morbidly obese individuals. It is unknown whether the control of diabetes is a
      secondary outcome from the treatment of obesity or a direct result of the
      duodenal-jejunal exclusion that both operations include. The aim of this study
      was to investigate whether duodenal-jejunal exclusion can control diabetes
      independently on resolution of obesity-related abnormalities. METHODS: A
      gastrojejunal bypass (GJB) with preservation of an intact gastric volume was
      performed in 10- to 12-week-old Goto-Kakizaki rats, a spontaneous nonobese model
      of type 2 diabetes. Fasting glycemia, oral glucose tolerance, insulin
      sensitivity, basal plasma insulin, and glucose-dependent-insulinotropic peptide
      as well as plasma levels of cholesterol, triglycerides, and free fatty acids were
      measured. The GJB was challenged against a sham operation, marked food
      restriction, and medical therapy with rosiglitazone in matched groups of animals.
      Rats were observed for 36 weeks after surgery. RESULTS: Mean plasma glucose 3
      weeks after GJB was 96.3 +/- 10.1 mg/dL (preoperative values were 159 +/- 47
      mg/dL; P = 0.01). GJB strikingly improved glucose tolerance, inducing a greater
      than 40% reduction of the area under blood glucose concentration curve (P <
      0.001). These effects were not seen in the sham-operated animals despite similar
      operative time, same postoperative food intake rates, and no significant
      difference in weight gain profile. GJB resulted also in better glycemic control
      than greater weight loss from food restriction and than rosiglitazone therapy.
      CONCLUSIONS: Results of our study support the hypothesis that the bypass of
      duodenum and jejunum can directly control type 2 diabetes and not secondarily to
      weight loss or treatment of obesity. These findings suggest a potential role of
      the proximal gut in the pathogenesis the disease and put forward the possibility
      of alternative therapeutic approaches for the management of type 2 diabetes.

PMID- 14685094
TI  - Diabetes: the evolution of a new paradigm.

PMID- 14685095
TI  - Robotic surgery: a current perspective.
AB  - OBJECTIVE: To review the history, development, and current applications of
      robotics in surgery. BACKGROUND: Surgical robotics is a new technology that holds
      significant promise. Robotic surgery is often heralded as the new revolution, and
      it is one of the most talked about subjects in surgery today. Up to this point in
      time, however, the drive to develop and obtain robotic devices has been largely
      driven by the market. There is no doubt that they will become an important tool
      in the surgical armamentarium, but the extent of their use is still evolving.
      METHODS: A review of the literature was undertaken using Medline. Articles
      describing the history and development of surgical robots were identified as were
      articles reporting data on applications. RESULTS: Several centers are currently
      using surgical robots and publishing data. Most of these early studies report
      that robotic surgery is feasible. There is, however, a paucity of data regarding
      costs and benefits of robotics versus conventional techniques. CONCLUSIONS:
      Robotic surgery is still in its infancy and its niche has not yet been well
      defined. Its current practical uses are mostly confined to smaller surgical
      procedures.

PMID- 14685096
TI  - Double endoscopic intraluminal operation for upper digestive tract diseases:
      proposal of a novel procedure.
AB  - BACKGROUND AND OBJECTIVE: Endoscopic treatment of digestive tract diseases, such
      as early esophageal and gastric neoplasia, has become increasingly popular in
      recent years as an alternative to surgical procedures in the hope of providing an
      improved quality of life for these patients. However, one of the limitations of a
      conventional endoscopic mucosal resection, such as an aspiration mucosectomy and
      a strip biopsy, has been the size of the lesions to be resected. Both an
      aspiration mucosectomy and strip biopsy are useful variants for removing flat
      lesions measuring less than 20 mm in maximal diameter. To overcome such
      limitations, we devised a double endoscopic intraluminal operation (DEILO), which
      enables us to resect mucosal lesions by using 2 fine endoscopes and monopolar
      shears. METHODS: DEILO was performed on patients with esophageal and gastric
      lesions measuring up to 40 mm in diameter. This novel technique is characterized
      by the use of 2 endoscopes (one for lifting the lesion and the other for cutting
      the lesions) inserted into the esophagus or stomach through an overtube. A
      mucosal resection is then performed by dissecting the mucosal margin with newly
      developed monopolar shears, thereby separating the mucosa from the submucosa.
      RESULTS: A total of 25 lesions in the esophagus (8 lesions) and stomach (17
      lesions) were resected by DEILO. The sizes of the esophageal lesions ranged from
      8 to 40 mm in diameter (mean, 21.1 mm) whereas gastric lesions ranged from 8 to
      30 mm (mean, 13.3 mm) in diameter, and histopathologic examinations revealed the
      resection margin to be clear and without any tumor. No complications or instances
      of recurrence were observed in this series. CONCLUSIONS: DEILO is considered to
      be feasible for the mucosal resection of esophageal and gastric lesions measuring
      more than 10 mm in diameter without submucosal invasion, whereas conventional
      endoscopic mucosal resection is indicated for such lesions measuring less than 10
      mm in size.

PMID- 14685097
TI  - A prospective study of common bile duct calculi in patients undergoing
      laparoscopic cholecystectomy: natural history of choledocholithiasis revisited.
AB  - OBJECTIVE: To define the incidence of problematic common bile duct calculi in
      patients undergoing laparoscopic cholecystectomy. SUMMARY BACKGROUND DATA: In
      patients selected for laparoscopic cholecystectomy, the true incidence of
      potentially problematic common bile duct calculi and their natural history has
      not been determined. We evaluated the incidence and early natural history of
      common bile duct calculi in all patients undergoing laparoscopic cholecystectomy
      with intraoperative and delayed postoperative cholangiography. METHODS: Operative
      cholangiography was attempted in all patients. In those patients in whom a
      filling defect was noted in the bile duct, the fine bore cholangiogram catheter
      was left securely clipped in the cystic duct for repeated cholangiography at 48
      hours and at approximately 6 weeks postoperatively. RESULTS: Operative
      cholangiography was attempted in 997 consecutive patients and was accomplished in
      962 patients (96%). Forty-six patients (4.6%) had at least one filling defect.
      Twelve of these had a normal cholangiogram at 48 hours (26% possible false
      positive operative cholangiogram) and a further 12 at 6 weeks (26% spontaneous
      passage of calculi). Spontaneous passage was not determined by either the number
      or size of calculi or by the diameter of the bile duct. Only 22 patients (2.2% of
      total population) had persistent common bile duct calculi at 6 weeks after
      laparoscopic cholecystectomy and retrieved by endoscopic retrograde
      cholangiopancreatography. CONCLUSIONS: Choledocholithiasis occurs in 3.4% of
      patients undergoing laparoscopic cholecystectomy but more than one third of these
      pass the calculi spontaneously within 6 weeks of operation and may be spared
      endoscopic retrograde cholangiopancreatography. Treatment decisions based on
      assessment by operative cholangiography alone would result in unnecessary
      interventions in 50% of patients who had either false positive studies or
      subsequently passed the calculi. These data support a short-term expectant
      approach in the management of clinically silent choledocholithiasis in patients
      selected for LC.

PMID- 14685098
TI  - Preoperative parameters expanding the indication of sphincter preserving surgery
      in patients with advanced low rectal cancer.
AB  - OBJECTIVE: To clarify the preoperative parameters of the required distal margin
      that can be applied to the criteria of sphincter-preserving surgery in rectal
      cancer. SUMMARY BACKGROUND DATA: Although aggressive sphincter-preserving
      surgery, including intersphincteric resection, is beginning to be applied to low
      rectal tumors, unexpected distal cancer spread might undermine local control in
      patients undergoing such a procedure. The 'two-centimeter rule' of distal
      clearance is predominant at present, whereas preoperative criteria to determine
      the individual required distal margin have not yet been established. METHODS:
      First, by reviewing 556 rectal cancers, promising risk parameters of intramural
      distal spread (IM) were selected and, subsequently, such parameters were examined
      in regard to whether they could be evaluated preoperatively. Furthermore, 80
      patients with lower rectal cancers located above the anal canal who were
      undergoing abdominoperineal resection were reviewed as to whether IM risk factors
      could be used as criteria to identify the low rectal cancer with or without anal
      canal involvement. RESULTS: IM was observed in 10.6% (IM >or= 10 mm: 2.3%) of the
      patients examined, and the incidence was higher in tumors with certain
      unfavorable histologic characteristics, including tumor "budding," in their
      submucosal region at the distal edge (24.4%) than in those with no such histology
      (5.3%). Regarding such unfavorable histology as IM risk factor, together with 3/4
      or more annularity and type 3 gross appearance, IM rates were 3.3% (IM >or= 10
      mm: 0.5%) in the no-risk group, 9.1% (IM >or= 10 mm: 1.7%) in the one-risk group,
      and 29.1% (IM >or= 10mm: 7.8%) in the multiple-risks group. These results were
      reproduced well even if such risk factors were evaluated endoscopically or
      histologically on preoperative biopsy specimens. Furthermore, no anal canal
      involvement was observed in 32 tumors without IM risk; however, microscopic
      cancer spread down to the anal canal, including that into outside of the internal
      sphincter muscle, was observed in 9.1% of tumors with one IM risk and in 26.7% of
      multiple-risk tumors. CONCLUSIONS: The preoperative evaluation of particular
      parameters related to IM enabled the accurate selection of rectal cancer to which
      the one-centimeter rule of distal clearance can be applied. This could allow us
      to expand the indication of sphincter preservation for very low rectal cancer
      patients.

PMID- 14685099
TI  - Laparoscopic versus open appendectomy: outcomes comparison based on a large
      administrative database.
AB  - OBJECTIVE: To compare length of hospital stay, in-hospital complications, in
      hospital mortality, and rate of routine discharge between laparoscopic and open
      appendectomy based on a representative, nationwide database. SUMMARY BACKGROUND
      DATA: Numerous single-institutional randomized clinical trials have assessed the
      efficacy of laparoscopic and open appendectomy. The results, however, are
      conflicting, and a consensus concerning the relative advantages of each procedure
      has not yet been reached. METHODS: Patients with primary ICD-9 procedure codes
      for laparoscopic and open appendectomy were selected from the 1997 Nationwide
      Inpatient Sample, a database that approximates 20% of all US community hospital
      discharges. Multiple linear and logistic regression analyses were used to assess
      the risk-adjusted endpoints. RESULTS: Discharge abstracts of 43757 patients were
      used for our analyses. 7618 patients (17.4%) underwent laparoscopic and 36139
      patients (82.6%) open appendectomy. Patients had an average age of 30.7 years and
      were predominantly white (58.1%) and male (58.6%). After adjusting for other
      covariates, laparoscopic appendectomy was associated with shorter median hospital
      stay (laparoscopic appendectomy: 2.06 days, open appendectomy: 2.88 days, P <
      0.0001), lower rate of infections (odds ratio [OR] = 0.5 [0.38, 0.66], P <
      0.0001), decreased gastrointestinal complications (OR = 0.8 [0.68, 0.96], P =
      0.02), lower overall complications (OR = 0.84 [0.75, 0.94], P = 0.002), and
      higher rate of routine discharge (OR = 3.22 [2.47, 4.46], P < 0.0001).
      CONCLUSIONS: Laparoscopic appendectomy has significant advantages over open
      appendectomy with respect to length of hospital stay, rate of routine discharge,
      and postoperative in-hospital morbidity.

PMID- 14685100
TI  - Reductive surgery plus percutaneous isolated hepatic perfusion for multiple
      advanced hepatocellular carcinoma.
AB  - OBJECTIVE: To evaluate the efficacy of a novel 2-stage treatment with reductive
      surgery plus percutaneous isolated hepatic perfusion (PIHP) for multiple
      hepatocellular carcinoma (HCC), which was previously unresectable. SUMMARY
      BACKGROUND DATA: Surgical resection is the treatment of choice for HCC, but the
      majority of patients with advanced HCC are not suitable candidates. PIHP is a
      minimally invasive surgery that allows high-dose regional chemotherapy of the
      liver, and our phase II studies have shown its profound efficacy for the local
      control of advanced HCC. METHODS: Twenty-five patients with multiple advanced HCC
      were enrolled in this prospective study. In the first stage, all patients
      underwent reductive hepatectomy: major hepatectomy in 13 patients and
      segmentectomy or less in 12. In 2 patients with subsegmentectomy, the
      retropancreatic and periportal metastatic lymph nodes were synchronously
      resected. Regardless of the type of hepatectomy, all patients routinely underwent
      cholecystectomy, and ligations of the right gastric artery and arterial
      collaterals of the remnant liver to increase the safety and efficacy of PIHP. In
      the second stage, PIHP with doxorubicin 60-120 mg/m2/treatment was planned for a
      period of 1 to 3 months after surgery. RESULTS: Of 25 enrolled patients, 22
      successfully underwent PIHP an average of 1.8 times for the local control of
      residual liver tumors. In the remaining 3 patients, PIHP was abandoned because 2
      had rapid disease progression and 1 had liver failure after surgery. In 22
      patients with the 2-stage treatment, 19 (86%) had objective local tumor control
      (10 complete remissions and 9 partial responses with a median response duration
      of 16 months). The actuarial survival rate of all 25 patients was 42% at 5 years.
      CONCLUSIONS: Reductive surgery plus PIHP produced a strong antitumoral effect on
      multiple advanced HCC, when liver function allows this concentrated treatment
      approach, and offers long-term survival in a subset of patients who were
      previously deemed to have unresectable disease.

PMID- 14685101
TI  - Intraoperative imprint cytologic evaluation of sentinel lymph nodes for lobular
      carcinoma of the breast.
AB  - BACKGROUND: The evaluation of sentinel lymph nodes (SLNs) from a woman with
      lobular cancer of the breast is frequently challenging. Intraoperative imprint
      cytology (IIC) is equivalent to frozen sectioning for rapid SLN evaluation and is
      advantageous because it is rapid, reliable, cost-effective, and conserves tissue.
      Metastatic lobular carcinoma is difficult to identify in SLN because of its low
      grade cytomorphology, its tendency to infiltrate lymph nodes in a single cell
      pattern, and because individual cells can resemble lymphocytes. We are unaware of
      any large published studies, using any technique, to evaluate SLN for lobular
      carcinoma. METHODS: A retrospective review of the intraoperative imprint cytology
      results of 678 SLN mapping procedures for breast carcinoma was performed. From
      this cohort, we studied SLN from cases of lobular carcinoma. These SLN were
      evaluated intraoperatively by either bisecting or slicing the SLN into 4-mm
      sections. Imprints were made of each cut surface and stained with hematoxylin and
      eosin and/or Diff-Quik. Permanent sections were evaluated with up to 4
      hematoxylin and eosin-stained levels and cytokeratin immunohistochemistry. IIC
      results were compared with final histologic results. RESULTS: Sixty-one cases of
      pure invasive lobular carcinoma were identified. Sensitivity was 52%, specificity
      was 100%, accuracy was 82%, negative predictive value was 78%. No statistically
      significant differences in sensitivity, specificity or accuracy were identified
      for the intraoperative detection of lobular carcinoma versus ductal carcinoma.
      The sensitivity for detecting macrometastases (more than 2 mm) was better than
      for detecting micrometastases, 73 versus 25%, respectively (P = 0.059).
      CONCLUSIONS: The sensitivity and specificity of IIC are similar to that of
      intraoperative frozen section evaluation. Therefore, IIC is a viable alternative
      to frozen sectioning when intraoperative evaluation is required. If SLN
      micrometastasis is used to determine the need for further lymphadenectomy, more
      sensitive intraoperative methods will be needed to avoid a second operation.

PMID- 14685102
TI  - Opposite effects of prostacyclin on hepatic blood flow and oxygen consumption
      after burn and sepsis.
AB  - BACKGROUND: Burn and sepsis are associated with hepatic ischemia and reperfusion
      injury. This study examines the hypothesis that postburn treatment with the
      vasodilator prostacyclin would be beneficial for hepatic perfusion and
      oxygenation. METHODS: Female pigs (n = 18, 20-25 kg) underwent laparotomy, during
      which ultrasonic flow probes were placed on the portal vein and the common
      hepatic artery. Catheters were inserted in the superior mesenteric and left
      hepatic veins. After 5 days, all animals were anesthetized and 12 of them
      received 40% total body surface area third-degree burn; 100 microg/kg Escherichia
      coli lipopolysaccharide (LPS) was intravenously administered 18 hours postburn.
      Burned animals were randomized to receive a constant infusion of iloprost (20
      ng/kg per minute) or an equivalent amount of carrier solution (normal saline).
      All animals were studied for 42 hours. RESULTS: Burn caused a 2.5-fold increase
      in hepatic arterial vascular resistance (HAVR) and a 39% decrease in hepatic
      arterial blood flow (HABF). Postburn administration of iloprost did not improve
      the hepatic arterial hemodynamics (1.8-fold increase in HAVR and 38% decrease in
      HABF). Post-LPS, HABF was significantly reduced to 22% of baseline and HAVR was
      15-fold increased (P < 0.05 vs. baseline, ANOVA). In contrast, iloprost-treated
      animals did not show hepatic arterial vasoconstriction, as both HABF and HAVR
      remained baseline values during the endotoxic phase (P < 0.05 vs. nontreated
      group, ANOVA). Postburn iloprost treatment yielded a significant improvement in
      post-LPS portal venous blood flow (PVBF, 79% of baseline vs. 45% of baseline in
      nontreated animals, P < 0.05, ANOVA). Portal venous pressure showed 16% and 56%
      increases after burn and endotoxin, respectively. Portal hypertension did not
      occur in iloprost-treated animals, as portal venous pressure remained within
      baseline range (P < 0.05 vs. nontreated group, ANOVA). Burn and endotoxemia
      resulted in a significant decrease of hepatic oxygen delivery (hDO2, 63% and 12%
      of baseline, respectively) and hepatic oxygen consumption (hVO2, 61% and 21% of
      baseline, respectively). Only during the postburn endotoxic phase, iloprost
      improved hDO2 and hVO2 (140% and 79%, respectively; P < 0.05 vs. nontreated
      group, ANOVA). CONCLUSIONS: Postburn prostacyclin treatment appears to have no
      beneficial effects on hepatic perfusion early postburn. However, during the late
      postburn endotoxic phase, prostacyclin seems to significantly improve hepatic
      total blood flow and oxygenation. In addition, prostacyclin treatment attenuated
      burn- and endotoxin-induced portal hypertension.

PMID- 14685103
TI  - Perioperative recombinant human granulocyte colony-stimulating factor
      (Filgrastim) treatment prevents immunoinflammatory dysfunction associated with
      major surgery.
AB  - OBJECTIVE: To examine the effects of perioperative rhG-CSF administration on
      immune function in patients subjected to major surgery. SUMMARY BACKGROUND DATA:
      Severe trauma, such as major surgery, initiates acute immunodysfunction which
      predisposes the patient towards infectious complications. METHODS: Sixty patients
      undergoing elective surgery received either recombinant human granulocyte colony
      stimulating factor/rh G-CSF (Filgrastim) or a placebo perioperatively. At several
      time points before and after the surgical intervention immunofunctional
      parameters were assessed. RESULTS Leukocyte counts and serum levels of anti
      inflammatory mediators (IL-1ra and TNF-R) were increased in Filgrastim-treated
      patients, while the post-operative acute phase response was attenuated. Monocyte
      deactivation (reduced TNF-alpha release and HLA-DR expression) and lymphocyte
      anergy (impaired mitogenic proliferation and reduced TH1 lymphokine release) were
      blunted and the incidence and severity of infectious complications were reduced.
      CONCLUSIONS: These results suggest that Filgrastim treatment reinforces innate
      immunity, enabling better prevention of infection. Thus, this unique combination
      of hematopoietic, anti-inflammatory and anti-infectious effects on the innate
      immune system warrants further study of clinical efficacy and sepsis prophylaxis.

PMID- 14685104
TI  - Surgical anatomy of the bile ducts at the hepatic hilum as applied to living
      donor liver transplantation.
AB  - OBJECTIVE: To evaluate anatomic variations of the biliary tree as applied to
      living donor liver transplantation. SUMMARY BACKGROUND DATA: Anatomic variability
      is the rule rather than the exception in liver surgery. However, few studies have
      focused on the anatomic variations of the biliary tree in living donor liver
      transplantation in relation to biliary reconstruction. METHODS: From November
      1992 to June 2002, 165 patients underwent major hepatectomy with extrahepatic
      bile duct resection; right-sided hepatectomy in 110 patients and left-sided
      hepatectomy in 55. Confluence patterns of the intrahepatic bile ducts at the
      hepatic hilum in the surgical specimens were studied. RESULTS: Confluence
      patterns of the right intrahepatic bile ducts were classified into 7 types. The
      right hepatic duct was absent in 4 of the 7 types and in 29 (26%) of the 110
      livers. Confluence patterns of the left intrahepatic bile ducts were classified
      into 4 types. The left hepatic duct was absent in 1 of the 4 types and in 1 (2%)
      of the 55 livers. CONCLUSIONS: In harvesting the right liver from a donor without
      a right hepatic duct, 2 or more bile duct stumps will be present in the plane of
      transection in the graft in 3 patterns based on their relation to the portal
      vein. Accurate knowledge of the variations in the hepatic confluence is essential
      for successful living donor liver transplantation.

PMID- 14685105
TI  - Survival following liver transplantation from non-heart-beating donors.
AB  - OBJECTIVE: To determine whether patient and graft survival following
      transplantation with non-heart-beating donor (NHBD) hepatic allografts is
      equivalent to heart-beating-donor (HBD) allografts. SUMMARY BACKGROUND DATA: With
      the growing disparity between the number of patients awaiting liver
      transplantation and a limited supply of cadaveric organs, there is renewed
      interest in the use of hepatic allografts from NHBDs. Limited outcome data
      addressing this issue exist. METHODS: Retrospective evaluation of graft and
      patient survival among adult recipients of NHBD hepatic allografts compared with
      recipients of HBD livers between 1993 and 2001 using the United Network of Organ
      Sharing database. RESULTS: NHBD (N = 144) graft survival was significantly
      shorter than HBD grafts (N = 26856). One- and 3-year graft survival was 70.2% and
      63.3% for NHBD recipients versus 80.4% and 72.1% (P = 0.003 and P = 0.012) for
      HBD recipients. Recipients of an NHBD graft had a greater incidence of primary
      nonfunction (11.8 vs. 6.4%, P = 0.008) and retransplantation (13.9% vs. 8.3%, P =
      0.04) compared with HBD recipients. Prolonged cold ischemic time and recipient
      life support were predictors of early graft failure among recipients of NHBD
      livers. Although differences in patient survival following NHBD versus HBD
      transplant did not meet statistical significance, a strong trend was evident that
      likely has relevant clinical implications. CONCLUSIONS: Graft and patient
      survival is inferior among recipients of NHBD livers. NHBD donors remain an
      important source of hepatic grafts; however, judicious use is warranted,
      including minimization of cold ischemia and use in stable recipients.

PMID- 14685106
TI  - Societal reintegration after liver transplantation: findings in alcohol-related
      and non-alcohol-related transplant recipients.
AB  - OBJECTIVE: To compare the degree of societal reintegration between alcohol
      related and non-alcohol-related liver transplant recipients. SUMMARY BACKGROUND
      DATA: Orthotopic liver transplantation (OLTX) is the treatment of choice for end
      stage liver disease of various etiologies. Returning patients to society to lead
      active and productive lives is a key goal of OLTX. METHODS: A questionnaire
      assessing societal reintegration was administered by phone to 84 alcoholic liver
      disease (ALD) OLTX recipients (ALDs) and 68 non-ALD OLTX recipients having
      undergone OLTX at a single-center urban not-for-profit teaching hospital. Sixty
      eight non-ALD OLTX recipients, serving as the control group (Controls), were
      matched to the ALDs by age, sex, and length of follow-up. Participation levels
      were assessed in the following areas: employment, homemaking, academic study,
      support of others through financial and/or care-giving efforts, and involvement
      in social or community groups and activities. RESULTS: Seventy-nine percent of
      ALDs and 81% of Controls were male. Median age was 53 years for ALDs and 54 years
      for Controls. Median length of follow-up for both groups separately was 52
      months. No significant differences were noted between ALDs and Controls in the
      proportion of employed individuals, homemakers, students, and supporters of
      others. Controls were significantly more likely than ALDs to be involved in
      structured social activities and routine volunteer work. CONCLUSIONS: Alcohol
      related and non-alcohol-related OLTX recipients appear to return to society to
      lead similarly active and productive lives. ALD OLTX recipients appear less
      likely to be involved in structured social activities and routine volunteer work
      than non-ALD OLTX recipients.

PMID- 14685107
TI  - Alabama coronary artery bypass grafting project: results from phase II of a
      statewide quality improvement initiative.
AB  - OBJECTIVE/BACKGROUND: This report describes the first round of results for Phase
      II of the Alabama CABG Project, a regional quality improvement initiative.
      METHODS: Charts submitted by all hospitals in Alabama performing CABG (ICD-9
      codes 36.10-36.20) were reviewed by a Clinical Data Abstraction Center (CDAC)
      (preintervention 1999-2000; postintervention 2000-2001). Variables that described
      quality in Phase I were abstracted for Phase II and data describing the new
      variables of beta-blocker use and lipid management were collected. Data samples
      collected onsite by participating hospitals were used for rapid cycle improvement
      in Phase II. RESULTS: CDAC data (n = 1927 cases in 1999; n = 2001 cases in 2000)
      showed that improvements from Phase I in aspirin prescription, internal mammary
      artery use, and duration of intubation persisted in Phase II. During Phase II,
      use of beta-blockers before, during, or after CABG increased from 65% to 76% of
      patients (P < 0.05). Appropriate lipid management, an aggregate variable,
      occurred in 91% of patients before and 91% after the educational intervention.
      However, there were improvements in 3 of 5 subcategories for lipid management
      (documenting a lipid disorder [52%-57%], initiating drug therapy [45%-53%], and
      dietary counseling [74%-91%]; P < 0.05). CONCLUSIONS: In Phase II, this statewide
      process-oriented quality improvement program added two new measures of quality.
      Achievements of quality improvement from Phase I persisted in Phase II, and
      improvements were seen in the new variables of lipid management and perioperative
      use of beta-blockers.

PMID- 14685108
TI  - Hospital coronary artery bypass graft surgery volume and patient mortality, 1998
      2000.
AB  - OBJECTIVE: To evaluate the association between annual hospital coronary artery
      bypass graft (CABG) surgery volume and in-hospital mortality. SUMMARY BACKGROUND
      DATA: The Leapfrog Group recommends health care purchasers contract for CABG
      services only with hospitals that perform >or=500 CABGs annually to reduce
      mortality; it is unclear whether this standard applies to current practice.
      METHODS: We conducted a retrospective analysis of the National Inpatient Sample
      database for patients who underwent CABG in 1998-2000 (n = 228738) at low (12-249
      cases/year), medium (250-499 cases/year), and high (>or=500 cases/year) CABG
      volume hospitals. Crude in-hospital mortality rates were 4.21% in low-volume
      hospitals, 3.74% in medium-volume hospitals, and 3.54% in high-volume hospitals
      (trend P < 0.001). Compared with patients at high-volume hospitals (odds ratio
      1.00, referent), patients at low-volume hospitals remained at increased risk of
      mortality after multivariable adjustment (odds ratio 1.26, 95% confidence
      interval = 1.15-1.39). The mortality risk for patients at medium-volume hospitals
      was of borderline significance (odds ratio 1.11, 95% confidence interval = 1.01
      1.21). However, 207 of 243 (85%) of low-volume and 151 of 169 (89%) of medium
      volume hospital-years had risk-standardized mortality rates that were
      statistically lower or comparable to those expected. In contrast, only 11 of 169
      (6%) of high-volume hospital-years had outcomes that were statistically better
      than expected. CONCLUSIONS: Patients at high-volume CABG hospitals were, on
      average, at a lower mortality risk than patients at lower-volume hospitals.
      However, the small size of the volume-associated mortality difference and the
      heterogeneity in outcomes within all CABG volume groups suggest individual
      hospital CABG volume is not a reliable marker of hospital CABG quality.

PMID- 14685110
TI  - Optimal restraint reduces the risk of abdominal injury in children involved in
      motor vehicle crashes.
AB  - BACKGROUND: The American Academy of Pediatrics has established guidelines for
      optimal, age-appropriate child occupant restraint. While optimal restraint has
      been shown to reduce the risk of injuries overall, its effect on specific types
      of injuries, in particular abdominal injuries, has not been demonstrated.
      METHODS: Cross-sectional study of children aged younger than 16 years in crashes
      of insured vehicles in 15 states, with data collected via insurance claims
      records and a telephone survey. A probability sample of 10927 crashes involving
      17132 restrained children, representing 210926 children in 136734 crashes was
      collected between December 1, 1998 and May 31, 2002. Restraint use was
      categorized as optimal or suboptimal based on current American Academy of
      Pediatrics guidelines. The outcome of interest, abdominal injury, was defined as
      any reported injury to an intra-abdominal organ of Abbreviated Injury Scale >or=2
      severity. RESULTS: Among all restrained children, optimal was noted in 59% (n =
      120473) and suboptimal in 41% (n = 83555). An associated abdominal organ injury
      was noted in 0.05% (n = 62) of the optimal restrained group and 0.17% (n = 140)
      of the suboptimal group. After adjusting for age and seating position (front vs.
      rear), optimally restrained children were more than 3 times less likely [odds
      ratio 3.51 (95% confidence interval, 1.87-6.60, P < 0.001)] as suboptimally
      restrained children to suffer an abdominal injury. Of note, there were no
      abdominal injuries reported among optimally restrained 4- to 8-year-olds.
      CONCLUSIONS: Optimally restrained children are at a significantly lower risk of
      abdominal injury than children suboptimally restrained for age. This disparity
      emphasizes the need for aggressive education efforts aimed not only at getting
      children into restraint systems, but also the importance of optimal, age
      appropriate restraint.

PMID- 14685109
TI  - Venous claudication in iliofemoral thrombosis: long-term effects on venous
      hemodynamics, clinical status, and quality of life.
AB  - OBJECTIVE: We evaluated the long-term impact of iliofemoral thrombosis (I-FDVT)
      on walking capacity, venous hemodynamic status, CEAP class, venous clinical
      severity, and quality of life, and determined the prevalence of venous
      claudication. MATERIALS AND METHODS: All patients with prior I-FDVT, assessed at
      our institution since 1990, were called for follow-up. Those with walking
      impairment due to arterial disease (ABI < 1.0 postexercise) or unrelated causes
      and those thrombectomized or thrombolyzed were excluded; 39 patients (22-83
      years, median 46 years) were included. Median follow-up was 5 years (range 1-23
      years). Investigation included classification in CEAP and Venous Clinical
      Severity Scoring (VCSS) systems, air-plethysmography (outflow fraction [OF],
      venous filling index [VFI], residual volume fraction [RVF]) and venous duplex,
      treadmill (3.5 km/h, 10%) to determine initial (ICD) and absolute (ACD)
      claudication distances, and quality of life assessment (SF-36). Nonaffected limbs
      of patients with unilateral I-FDVT (37 of 39) comprised the control group. Data
      are presented as median and interquartile range. RESULTS: A total of 81% of limbs
      with I-FDVT had superficial and deep reflux and 19% superficial reflux; reflux in
      control limbs was 29.7% (P < 0.001) and 27% (P > 0.2), respectively; 43.6% (17 of
      39; 95% CI, 27-60%) of patients developed venous claudication ipsilateral to I
      FDVT (ICD: 130 m, range 105-268 m), compelling 15.4% (6 of 39; 95% CI, 3.5-27%)
      to discontinue treadmill (ACD: 241 m, range 137-298 m). Limbs with prior I-FDVT
      had a lower OF (37%, range 32.2-43%; P < 0.001), abnormally higher VFI (3.8 mL/s,
      range 2.5-5.7 mL/s; P < 0.001), and RVF (45%, range 32.5-51.5%; P = 0.006), and
      clinical impairment in CEAP and VCSS systems (P < 0.0001). Patients with I-FDVT
      had impaired physical functioning (P = 0.02) and role (P = 0.033), general health
      (P = 0.001), social function (P = 0.047), and mental health (P = 0.043).
      CONCLUSIONS: A total of 43.6% of those with prior I-FDVT developed venous
      claudication compelling interruption of walking in 15.4%. Prior I-FDVT caused
      outflow impairment and a large residual venous volume and reflux, resulting in
      marked clinical and quality of life compromise. Standardized challenge enabled
      discrimination of those with clinically relevant impairment.

PMID- 14685111
TI  - Nursing has lost its essence: care is being demeaned.

PMID- 14685112
TI  - It is important that managers target stress in the workplace.

PMID- 14685113
TI  - Paediatric staff nurse who did not improve after education.

PMID- 14685114
TI  - 12-lead ECG interpretation and chest pain management: 1.
AB  - The National Service Framework for Coronary Heart Disease provides guidance on
      important aspects of therapy that may make a substantial difference to patient
      care (Department of Health (DoH), 2001). It highlights the need to identify and
      fast-track patients with an acute coronary syndrome so that thrombolysis or
      appropriate interventional care can take place as soon as possible, to optimize
      myocardial salvage and reduce door-to-needle time (DoH, 2001; Castle, 2002). It
      is therefore extremely important that nurses in acute clinical areas are able to
      record and interpret 12-lead electrocardiograms so that the treatment modality
      can be initiated as soon as possible, leading to better clinical outcomes for
      this patient group. Although nurses work within a healthcare team, it is often
      the nurse who initially assesses, implements and coordinates care for patients
      with chest pain, be it in the emergency department, cardiac unit, general ward
      setting or general practice.

PMID- 14685115
TI  - The effects of stress on wound healing and leg ulceration.
AB  - Stress is a universal phenomenon, which has been the focus of much investigation
      over the past five decades. Much has been discovered about the physiological
      responses to stress. This review examines the concept of stress in relation to
      its effect on wound healing. An online literature search was carried out using
      the databases Medline, Cinahl and Pubmed and the key words stress and wound
      healing, and stress and leg ulceration. The rationale for specifically examining
      leg ulceration resulted from the author's interest in this wound type and also
      the volume of associated literature on the topic published to date. Stress has
      been demonstrated to have an adverse effect on a variety of natural resistance
      responses and specific immunological modifications in animal and man alike,
      causing, for example, reduced inflammatory response, susceptibility to infection
      and decreased cytokine production (Cohen et al, 1988; Sheridan et al, 1991).
      Stress and its effects on growth factor regulation have led theorists to examine
      whether stress adversely affects wound healing (Glaser et al, 1999). Much of the
      research as examined acute wounds, although causal inferences may be drawn from
      the wealth of qualitative research examining the effects of venous ulceration. To
      date, very little has been conducted in the relatively new area of stress and
      wound healing. Further investigations are required to prove that stress elicits
      an immunological response affecting the biological markers of wound healing and
      thus validates the theory that stress may have a negative impact on healing
      itself. Causal relationships may be postulated between stress and healing in leg
      ulceration.

PMID- 14685116
TI  - New flexible healthcare roles and the purpose of nursing.
AB  - Current policy aims for healthcare professionals to be trained to work across
      traditional boundaries. The intention of this move is to improve understanding
      between the professions, to enhance patient care, to promote job satisfaction and
      to achieve cost-effectiveness (Department of Health (DoH), 2000). However, there
      is a risk that the blurring of professional boundaries may result in a loss of
      the unique contributions of specific professions. In the case of nursing, this
      may mean that the provision of care that is based on holism, empowerment, and
      partnership may be lost. This may have an adverse effect on nursing morale and
      job satisfaction as well as patient care. Nurses need to be clear about the
      nature of their professional priorities and remit. Where these are incongruent
      with a culture in which meeting quantifiable targets is a major focus, they must
      be able to articulate clearly the importance of the unquantifiable and humanistic
      aspects of care.

PMID- 14685117
TI  - Medicinal products and consent by young persons to treatment.

PMID- 14685118
TI  - Mental health nursing students' rationales for self-disclosure: 2.
AB  - This is the second of two articles that consider the findings of a study
      exploring mental health nursing students' reasons for their use and non-use of
      self-disclosure in their relationships with patients. The first article (Vol
      12(20): 1220-7) described the background to the deployment of this skill within
      therapeutic approaches, the paucity of literature discussing its use within
      nursing, the methods employed in this study and the findings for mental health
      nursing students' reasons for using the skill. This second article focuses on
      student's reasons for not deploying this skill, which are discussed in the
      following categories: 'crossing the line', 'unhelpful', 'name, rank and serial
      number' and 'students' vulnerability'. A discussion of the findings from both
      articles and their implications is offered.

PMID- 14685119
TI  - Overcoming barriers to delivering information to cancer patients.
AB  - The benefits of providing high quality information to patients are well
      documented, and include promoting active participation in decision-making and
      improved psychological and physical well-being. Within this article the need for
      high quality information is discussed and some of the common pitfalls in
      producing patient information are examined and suggestions for avoiding these
      pitfalls are proposed. The article looks at some of the problems in ensuring that
      those people who require information have access to it, specifically the
      potential barriers that may arise because of ethnic background, gender and social
      class, and recommendations to reduce the impact of such factors are made. The
      implications for the practice of all healthcare professionals caring for people
      with cancer are evident.

PMID- 14685120
TI  - New nursing roles must retain nursing's principles.

PMID- 14685121
TI  - Intravenous therapy is not being carried out effectively.

PMID- 14685122
TI  - Every child matters: some key issues for health services.

PMID- 14685123
TI  - Nurse who failed to ensure patient received adequate analgesia.

PMID- 14685124
TI  - The meaning of caring in the practice of intensive care nursing.
AB  - Caring is perceived as human behaviour that includes cognitive, affective,
      psychomotor and administrative skills within which professional caring may be
      expressed. It is a vital resource within the highly technological area of the
      intensive care unit (ICU). The terms care and caring are predominantly used to
      describe the inherent work and value of nursing. Nursing is a nurturing
      profession and caring is the essential component of its holistic practice,
      especially with the critically ill patient. The concept of caring in the ICU is
      central to the social relationship between the nurse, the patient and his/her
      relatives. Although caring is not unique to nursing, there is substantive,
      existing and developing knowledge related to caring in nursing. The concept of
      caring has been extensively explored in the literature. However, there is still
      little clarity in the understanding, description, relevance or function of caring
      in nursing.

PMID- 14685125
TI  - Interventions to avoid maceration of the skin and wound bed.
AB  - In the course of managing exuding wounds, particularly chronic wounds, failure to
      deal adequately with exudate can lead to exposure of the peri-wound skin to
      exudate and hence damage. This results in maceration of the skin and wound bed.
      Maceration is a largely under-recognized problem and one of the causes of delayed
      wound healing. Previous articles have focused on the nature and causes of
      maceration. This article describes a wide variety of wounds and skin conditions
      in which maceration might be present, or develop, during treatment, together with
      some strategies for avoiding maceration and the evidence base supporting them. It
      is only by becoming familiar with the various presentations of maceration, and
      with prophylactic treatment measures, that practitioners can avoid the increased
      costs and morbidity associated with it.

PMID- 14685126
TI  - Diabetes: classification and strategies for integrated care.
AB  - This article is the third in a series of three in-depth literature reviews on
      diabetes. The first article (Vol 12(18): 1091-5) detailed the history of diabetes
      from the first recorded mention of the disease in the Ebers papyrus through to
      the discovery of insulin. The second (Vol 12(19): 1137-41) dealt with the history
      of insulin over the past 80 years and the development of possible alternatives.
      This final article in the series details the new classifications for diabetes and
      addresses the aetiology, pathophysiology and complications of the disease. While
      discussing both type 1 and type 2 diabetes, the article concentrates on the newly
      defined type 1 diabetes mellitus. An examination of the recently released
      National Service Framework for Diabetes: Delivery Strategy (DoH, 2003) is
      included, healthcare provision is discussed, as is the role of the diabetes
      specialist nurse. An insight is given into the challenges and opportunities
      available for healthcare practitioners to work in partnership to reform the way
      in which diabetes services are managed.

PMID- 14685127
TI  - The problems of interprofessional healthcare practice in hospitals.
AB  - This article outlines the problems of interprofessional practice in the hospital
      setting. It examines the difficulties associated with competing ideologies and
      aims, inequalities in power relations, communication and role confusion and
      overlap. Within the hospital setting such problems often arise although the roots
      of the problem may go unacknowledged. The ways in which the problems occur in the
      hospital setting are considered, as is the underlying cause of such problems.
      Case studies will be used to analyse how the problems arise and ways in which
      they might be addressed.

PMID- 14685128
TI  - Mental health nursing students' rationales for self-disclosure: 1.
AB  - This study explored mental health nursing students' rationales for choosing
      whether or not to self-disclose in therapeutic encounters with patients. Using a
      two-item questionnaire, data were collected from a convenience sample of 162
      preregistered students recruited from two universities in the UK. Content
      analysis of the data produced three categories for using self-disclosure:
      "building a therapeutic relationship", "similar experiences" and "appropriate
      information". Reasons for not self-disclosing fell into four categories:
      "crossing the line", "unhelpful", "name, rank and serial number" and "students'
      vulnerability". The research findings suggest that both therapeutic and personal
      reasons are involved in the decision to use self-disclosure. This article, the
      first of a two-part series, outlines the background, research methods and nurses'
      reasons for using self-disclosure. The second article will present students'
      reasons for not using self-disclosure and a discussion of the findings and their
      implications.

PMID- 14685129
TI  - Medicinal products and consent by mentally incapacitated patients.

PMID- 14685130
TI  - Dedication and problems of nurses in Palestine.

PMID- 14685131
TI  - Stunts aside, hunger is a serious issue.

PMID- 14685132
TI  - Use of Entonox in the community for control of procedural pain.
AB  - Nitrous oxide gas, mixed 50:50 with oxygen, is an effective and safe analgesic
      which, although widely used in many areas of clinical practice, has not been
      fully recognized in the community setting for painful procedures. The reasons why
      it has not been implemented and used to the patient's advantage have been
      suggested as apathy, lack of confidence, lack of knowledge and lack of resources.
      The author describes how, following a review of the literature pertaining to its
      use in other clinical areas, she has successfully introduced nitrous oxide/oxygen
      into her trust, with positive results.

PMID- 14685133
TI  - The public health roles of health visitors and school nurses: a survey.
AB  - This article describes a qualitative study that examined the family centre public
      health role of health visitors and the child-centre public health role of school
      nurses. A telephone survey of key health visitor and school nurse informants in
      the West Midlands was undertaken. Respondents to the survey were asked to give
      examples of practice that related to Holman's (1992) public health typology. A
      wealth of data were obtained, which included 344 different examples of practice
      interventions. The majority of examples of practice given by the respondents were
      categorized as primary preventive interventions. The least represented concerned
      community empowerment and health protection. The findings of the survey give
      evidence of the current transitional nature health visitor and school nurse
      practice. Identified is some reorientation in practice and adoption of currently
      advocated models of public health, which have community participation,
      empowerment, and health protection as essential features.

PMID- 14685134
TI  - Stoma siting: what the community nurse needs to know.
AB  - Stoma siting is often regarded as the most important part of preoperative
      preparation. Marking the abdominal skin at the proposed stoma site takes place
      after a period of assessment, discussion, observation, consideration and
      evaluation that will have begun on the first meeting between the patient and the
      nurse. The siting procedure is a joint decision made between the patient and the
      nurse about the most suitable place for their stoma. The position of the stoma
      should allow the patient to manage it independently and to resume their normal
      activities after recovery. The success of the stoma can depend on the site and
      its condition. The purpose of this article is to describe and discuss the siting
      process and how it benefits the patient. Community nurses should gain a greater
      understanding of the issues involved, as well as the considerations for both the
      nurse and the patient. This article is intended to help the community nurse feel
      more aware of the issues involved in siting, and feel more prepared to assist the
      patient to prepare for and begin their life with the stoma. The outcome and
      effects of a 'poorly' or 'less than ideally' sited stoma (e.g. formed during
      emergency surgery), and its care and management will also be discussed.
      Illustrations have been included to assist the reader through the process of
      siting.

PMID- 14685135
TI  - Generosity or stealing? When accepting a gift can be theft.

PMID- 14685136
TI  - New insulin analogues and their impact on diabetes care.
AB  - The rising incidence of diabetes means that it is no longer viable for patients
      to be treated solely within the secondary care setting and primary health-care
      professionals, including community nurses working within community-based diabetes
      clinics, are likely to continue to take on greater responsibility for the
      assessment and management of patients with diabetes. This article discusses
      recent advances in insulin therapy--namely the advent of the new insulin
      analogues--and examines their likely impact on community nurses in terms of
      improved time management and quality of care for patients with diabetes on
      patients in terms of improved quality of care.

PMID- 14685137
TI  - So you want to do research? 4: An introduction to quantitative methods.
AB  - This fourth article of a series of six focuses on some of the key aspects of
      quantitative research methods. Starting with a review of what quantitative
      research is, the distinguishing characteristics of experimental and non
      experimental research strategies, the different approaches for collecting data
      including self-completion questionnaires, interviews and scales, together with
      their respective strength and weaknesses are discussed. The differences between
      probability and non-probability sampling and the different methods for selecting
      a sample are described. Aspects of quantitative data analysis are briefly
      reviewed and the concepts of reliability and validity are described in the
      context of ensuring rigour in the research design. Finally, some guidance on the
      reporting the findings from quantitative research is provided.

PMID- 14685138
TI  - Getting the message across: Valuing People.

PMID- 14685139
TI  - Guidelines for infection control in dental health-care settings--2003.
AB  - This report consolidates previous recommendations and adds new ones for infection
      control in dental settings. Recommendations are provided regarding 1) educating
      and protecting dental health-care personnel; 2) preventing transmission of
      bloodborne pathogens; 3) hand hygiene; 4) personal protective equipment; 5)
      contact dermatitis and latex hypersensitivity; 6) sterilization and disinfection
      of patient-care items; 7) environmental infection control; 8) dental unit
      waterlines, biofilm, and water quality; and 9) special considerations (e.g.,
      dental handpieces and other devices, radiology, parenteral medications, oral
      surgical procedures, and dental laboratories). These recommendations were
      developed in collaboration with and after review by authorities on infection
      control from CDC and other public agencies, academia, and private and
      professional organizations.

PMID- 14685140
TI  - Influence of hormones and growth factors on lens protein composition: the effect
      of dexamethasone and PDGF-AA.
AB  - PURPOSE: To investigate the effect of hormones and ocular growth factors on the
      expression of alpha-, beta-, and gamma-crystallins in rat lens epithelial and
      fiber cells. METHODS: PDGF-AA, EGF, NGF, M-CSF, BMP-2, BMP-4, dexamethasone, and
      estrogen were tested for their ability to alter the spectrum of crystallins in
      explanted newborn rat lens epithelial cells or in vitro differentiating newborn
      rat lens fiber cells. The accumulation of alphaA-, aB-, betaA3/1-, betaB2-, and
      gamma-crystallin was measured by western blot and dot blot analysis. The
      morphology of the rat lens explants after culture was examined by hematoxylin
      eosin staining, while crystallins were localized by immunofluorescence. RESULTS:
      Only dexamethasone and PDGF-AA showed an effect on relative crystallin levels. In
      the presence of dexamethasone the amount of alphaB-crystallin was increased in
      lens epithelial cells, but dexamethasone did not affect the crystallin spectrum
      in fiber cells. In rat lens epithelial explants cultured with PDGF-AA an increase
      in beta- and gamma-crystallin expression was seen. The spectrum of beta- and
      gamma-crystallins synthesized differed from that present in lens fiber cells. The
      cells expressing beta- and gamma-crystallin after culture with PDGF-AA were
      scattered in the epithelial cell layer and retained an epithelial morphology.
      PDGF-AA did not change the spectrum of crystallins synthesized in lens fiber
      cells but did enhance the rate of fiber cell differentiation, in agreement with
      results of others. CONCLUSIONS: Both dexamethasone and PDGF-AA influence
      crystallin gene expression in cultured rat lens epithelial cells. Dexamethasone
      enhances the expression of alphaB-crystallin while culturing in the presence of
      PDGF-AA caused an increase in beta- as well as gamma-crystallin synthesis. Since
      at least the gamma-crystallin genes are known to be silenced in epithelial cells
      by DNA methylation, PDGF-AA may be able to induce one of the steps towards fiber
      cell differentiation in some epithelial cells.

PMID- 14685141
TI  - Expression of cytokine signal transduction components in the postnatal mouse
      retina.
AB  - PURPOSE: Members of the ciliary neurotrophic factor (CNTF) family of cytokines
      have been shown to influence neuronal differentiation during retinal development
      and enhance cell survival in various retinal degeneration models. However, the
      cellular mechanism of CNTF signaling and the target cell types for CNTF in the
      developing retina remain unidentified. The purpose of this study is to
      characterize expression patterns of proteins involved in cytokine signal
      transduction in the mouse retina, thus to assess the potential responsiveness of
      different retinal cell types to CNTF-like cytokine signals. METHODS: The
      expression profiles of various cytokine signal transduction components, including
      receptor subunits CNTF receptor alpha (CNTFRa) and gp130, intracellular protein
      kinases, Jak2 and Tyk2, as well as latent transcription factors, STAT1 and STAT3,
      were determined by immunohistochemical staining of mouse retinal sections derived
      from different postnatal stages. In addition, the distribution of ERK was studied
      by immunofluorescent staining. RESULTS: In the neonatal retina, intense staining
      signals for gp130, CNTFRalpha, Jak2, Tyk2, STAT1, and STAT3 were present in the
      differentiated ganglion cell layer and the developing inner plexiform layer of
      the mouse retina. Detectable staining signals were also observed in the
      ventricular zone of the early postnatal mouse retina. From P5 to P10, cytokine
      signaling molecules also accumulated in the developing outer plexiform layer. In
      the adult retina, cytokine signaling components examined were localized to the
      ganglion cell layer, the inner nuclear layer, and the two plexiform layers. In
      addition, regions corresponding to the inner and/or outer segments of the
      photoreceptor cells showed positive staining for cytokine signaling components.
      In contrast, the ERK2 protein kinase was found throughout the neonatal retina. In
      the mature retina, ERK2 was concentrated in the ganglion cells and the inner
      plexiform layer, while a lesser expression of ERK2 was detected in the inner
      nuclear layer, the outer plexiform layers, and the outer nuclear layer.
      CONCLUSIONS: In the neonatal mouse retina, signaling components of the Jak-STAT
      pathway and ERK2 are differentially expressed. All cytokine signaling components
      included in this study are expressed in the differentiated inner retina as well
      as in cells occupying the ventricular zone, suggesting that both postmitotic
      neurons and proliferative progenitors may directly respond to CNTF-like cytokines
      during postnatal development. The distribution of cytokine signaling pathway
      components in the adult mouse retina is consistent with previous findings that
      ganglion cells and Muller glia are the primary target cell types for CNTF.

PMID- 14685142
TI  - Investigation of albinism genes in congenital esotropia.
AB  - PURPOSE: Esotropia is a feature of albinism. Amongst esotropic patients there may
      be mild unrecognised albinos. Oculocutaneous albinism shares several clinical
      features with congenital esotropia. It is well known that mammals with
      oculocutaneous albinism have misrouted retinal ganglion cell axons, most likely
      caused by the absence of melanin or DOPA during development. We investigated the
      hypothesis that mutations in the albinism genes Tyrosinase, the P Gene, and TYRP1
      may also be responsible for congenital esotropia via a similar mechanism.
      METHODS: We screened these three genes in 21 families with congenital esotropia
      using single stranded conformational polymorphism analysis. RESULTS: No rare
      sequence variants segregating with esoptopia were detected. A novel silent
      mutation of the TYRP1 gene was identified in one pedigree but is not likely to be
      causative. Several previously reported common polymorphisms were detected but do
      not segregate with disease in this population. CONCLUSIONS: Rare mutations of
      these genes do not appear to be responsible for congenital esotropia. Although we
      found no evidence for segregation of common variants with disease, these require
      further investigation for a possible contribution to a complex threshold model.
      Several lines of evidence indicate a genetic componenet of congenital esotropia,
      however, this is the first investigation of candidate genes for this disorder.

PMID- 14685143
TI  - Permissive glycan support of photoreceptor outer segment assembly occurs via a
      non-metabolic mechanism.
AB  - PURPOSE: We have previously demonstrated that in RPE-deprived retinas, lactose,
      galactose, and structurally related glycans support the proper assembly of
      nascent photoreceptor outer segment membranes. Other glycans such as mannose and
      glucose have no effect on this process. While the ability to support outer
      segment assembly is highly specific, all of the permissive glycans we have tested
      are able to enter metabolic pathways within the retinal cells, thus the mechanism
      by which the glycans are functioning is still ambiguous. The present study was
      undertaken to determine if permissive glycan-mediated support of photoreceptor
      outer segment assembly occurred via a non-metabolic mechanism and if the
      phenomenon was reversible. METHODS: The RPE was removed from isolated Xenopus
      laevis embryonic eyes that were allowed to complete differentiation in (1) Niu
      Twitty medium, (2) Niu-Twitty supplemented with 5x10-3 M lactose or mannose, (3)
      Niu-Twitty supplemented with lactose and 3H-galactose, (4) Niu-Twitty medium
      supplemented with isopropyl beta-D-thiogalactopyranoside (IPTG) at concentrations
      spanning five orders of magnitude, or (5) Niu-Twitty medium containing lactose or
      IPTG to which 3H-leucine was added for 2 days followed by an additional 2 days in
      Niu-Twitty alone. Control RPE-deprived and RPE-supported retinas were included
      for comparison. Under all experimental conditions, retinal photoreceptors were
      evaluated to determine the level of organized folding of outer segment membranes.
      RESULTS: Outer segment membranes of RPE-deprived retinas exposed to lactose were
      significantly more organized than both control RPE-deprived retinas and those
      exposed to mannose. In eyes exposed to the radiolabeled metabolizable glycan, the
      majority of the sugar was incorporated into Muller cells. IPTG, a non
      metabolizable form of galactose, promoted the formation of organized outer
      segment assembly similar to lactose although at a 100 fold reduced concentration
      compared to metabolizable permissive glycans. Both IPTG and lactose supported
      outer segment assembly in a step-wise fashion with maximal support at 5x10(-5) M
      and 5x10(-3) M, respectively. Removal of the permissive glycans resulted in loss
      of support of outer segment assembly. CONCLUSIONS: The ability of both lactose
      and IPTG to support outer segment assembly in the absence of the RPE is dose
      dependent and the effect of these sugars upon membrane folding is reversible.
      Moreover, this effect is supported by a non-metabolic mechanism and is therefore
      not accounted for by simple provision of an energy source.

PMID- 14685144
TI  - Exacerbation of TGF-beta-induced cataract by FGF-2 in cultured rat lenses.
AB  - PURPOSE: Culturing rat lenses with transforming growth factor-beta (TGFbeta)
      results in the formation of anterior, opaque subcapsular plaques which exhibit
      many of the features of human subcapsular cataract. The present study was
      undertaken to determine whether this process is influenced by the presence of
      fibroblast growth factor (FGF), a normal component of the lens environment in
      situ. METHODS: Rat lenses were cultured for 4-8 days with TGFbeta-2, alone or in
      combination with FGF-2, PDGF-AA, or the growth factor inhibitors poly(4
      styrenesulfonic acid) (PSS) and suramin. Responses were assessed by monitoring
      opacification, by routine histology and immunolocalization of markers for
      fibrotic change (a-smooth muscle actin, fibronectin, and type I collagen), or by
      measuring DNA accumulation in the epithelial region. RESULTS: Supplementing
      TGFbeta at a barely cataractogenic dose with 2.5-30 ng/ml FGF-2 resulted in a
      very strong opacification response. The exceptionally large plaques that formed
      were similar histologically to those induced by TGFbeta alone at higher
      concentrations and showed immunoreactivity for all markers. PDGF at a
      concentration equivalent to FGF in terms of proliferative potential did not
      demonstrate this effect. Addition of either PSS or suramin reduced the
      opacification response induced by a cataractogenic dose of TGFbeta alone.
      CONCLUSIONS: FGF has been identified as a factor capable of exacerbating the
      cataractogenic effects of TGFbeta. Thus FGF inhibitors, as well as TGFbeta
      inhibitors, have the potential to protect the lens against TGFbeta-induced
      cataractous changes.

PMID- 14685145
TI  - Differential distribution of vesicle associated membrane protein isoforms in the
      mouse retina.
AB  - PURPOSE: Many proteins associated with synaptic vesicle exocytosis are
      differentially distributed among synapses in the retina and elsewhere in the
      central nervous system. The synapse-specific distribution of these proteins and
      their isoforms is thought to contribute to synapse-specific functional
      differences. Vesicle-associated membrane protein (VAMP, also known as
      synaptobrevin) is an integral synaptic vesicle membrane protein that is part of
      the fusion core complex needed for docking and fusing of synaptic vesicles at the
      synaptic active zone. Two VAMP isoforms have been identified that are considered
      to be synaptic, VAMP-1 and VAMP-2, however their distributions among the various
      synapses in the mammalian retina have not been characterized. METHODS: Single-
      and double-labeling immunocytochemistry was used to investigate the distribution
      of the synaptic VAMP isoforms, VAMP-1 and VAMP-2, in the mouse retina. RESULTS:
      VAMP-2 was the predominant isoform in both synaptic layers. Double-labeling
      studies using conventional and ribbon-synapse-specific markers showed that VAMP-2
      was broadly distributed among conventional and ribbon synapses. In contrast, the
      distribution of VAMP-1 was very limited. In the outer retina, only weak labeling
      was present in photoreceptor terminals. In the inner retina, labeling for VAMP-1
      was found in the dendrites, cell bodies, and axons of some ganglion cells, as
      demonstrated by double labeling with the ganglion cell markers, microtubule
      associated protein-1 and Brn-3a. VAMP-1 labeling did not colocalize with amacrine
      or bipolar cell markers, nor did it colocalize with other pre-synaptic markers,
      suggesting that VAMP-1 is not associated directly with neurotransmitter release
      in the inner retina. Labeling for VAMP-1 identified a set of large ganglion cells
      that ramified in the mid-IPL (inner plexiform layer), suggesting that they may
      show ON-OFF responses. Some of these cells had cell bodies displaced to the inner
      nuclear layer. The dendrites of the large VAMP-1-immunoreactive ganglion cells
      did not co-stratify with the cholinergic plexuses of the starburst amacrine cells
      (labeled for choline acetyltransferase) and therefore are unlikely to show
      directional selectivity. However, these cells are likely to receive input from
      bipolar cells and a population of putative glutamatergic amacrine cells.
      CONCLUSIONS: VAMP-1 and VAMP-2 are differentially distributed among the synapses
      of the mouse retina. VAMP-2 is the predominant isoform and is widely expressed at
      ribbon and conventional synapses in both plexiform layers. VAMP-1 expression in
      the mouse retina is much more limited and is not restricted to presynaptic
      terminals. In the OPL, VAMP-1 is co-expressed with VAMP-2 presynaptically in
      photoreceptor terminals. However, VAMP-1 expression in the IPL is associated with
      ganglion cells and does not appear to be localized to presynaptic terminals. VAMP
      1 is a specific marker for a set of large ganglion cells and displaced ganglion
      cells that ramify in the mid-IPL and are likely to have ON-OFF physiology.

PMID- 14685146
TI  - Sources of PDGF expression in murine retina and the effect of short-term
      diabetes.
AB  - PURPOSE: Progressive dysfunction and death of vascular smooth muscle cells and
      pericytes is a pathophysiological hallmark of diabetic retinopathy, although the
      underlying mechanisms behind this process remain ill-defined. The multifunctional
      peptide platelet-derived growth factor (PDGF) is known to act as an important
      survival factor for both of these vascular cell-types at times of physiological
      stress. The retinal cell source(s) of PDGF remain unknown. It is important to
      understand how diabetes alters expression of this important growth factor.
      METHODS: Streptozotocin-diabetes was established in C57 mice. Following 8 weeks
      of sustained diabetes, the eyes were enucleated and in situ hybridization was
      used to localize expression of PDGF-A and PDGF-B chains in retina from both
      diabetic and non-diabetic controls. mRNA levels for both forms of PDGF, and their
      cognate PDGF-alpha and PDGF-beta receptors, were also quantified using real-time
      PCR. RESULTS: In situ hybridization demonstrated that PDGF-A and PDGF-B were
      predominantly expressed by the retinal ganglion cells/nerve fibre layer in both
      normal and diabetic mice, and this localization pattern did not alter in
      diabetes. PDGF-A receptor was expressed exclusively in the ganglion cell layer of
      the retina while PDGF-B receptor was mostly localized to the Muller cell end-feet
      at the internal limiting membrane with lesser immunoreactivity in the ganglion
      cells, inner plexiform layer, and inner nuclear layer. PDGF-A and PDGF-alpha
      receptor mRNA expression levels remained unaltered between treatment groups,
      although retinal immunolocalization patterns between both receptors was distinct.
      However, there was a significant decrease of PDGF-B mRNA levels in diabetic
      retina when compared to non-diabetic controls (p<0.001), although there was no
      significant difference in PDGF-alpha receptor(insert space) expression.
      CONCLUSIONS: Previous studies have shown PDGF expression in a range of cell-types
      during retinal development, but these results confirm ganglion cells as the
      principal PDGF source in mature retina. It may be significant that diabetes can
      reduce PDGF-B mRNA expression since this may have serious implications for
      vascular survival during diabetic retinopathy progression.

PMID- 14685147
TI  - Growth of the postnatal rat retina in vitro: quantitative RT-PCR analyses of mRNA
      expression for photoreceptor proteins.
AB  - PURPOSE: To investigate whether previously reported changes in protein expression
      of middle and long (M/L) and short (S) wavelength cone opsin pigments in cultured
      retina are correlated with changes in their gene expression. Additionally, to
      elucidate the importance of a functional retinal pigment epithelium for the
      development of photoreceptor outer segments. METHODS: Neonatal rat retinas were
      maintained in culture for 11 days and either fixed in 4% paraformaldehyde for
      immunohistochemistry or prepared for RNA extraction, reverse transcription
      polymerase chain reaction (RT-PCR), and quantitative RT-PCR. S-cone and M/L-cone
      photoreceptors as well as rod photoreceptors were immunohistochemically
      identified using specific antibodies. Peanut agglutinin (PNA)-lectin
      histochemistry was used to identify interphotoreceptor matrix associated with
      cone photoreceptors. Immunolabeling for ED-1 and RPE65 was performed in
      combination with PNA-lectin staining to examine interactions between
      photoreceptor cells and the retinal pigment epithelium. Relative estimates of
      mRNA expression levels for M/L-opsin, S-opsin, recoverin, and rhodopsin in normal
      and cultured retina were determined by using quantitative RT-PCR. RESULTS: Strong
      immunolabeling for recoverin and rhodopsin accumulated in outer segments as well
      as photoreceptor somata in vitro. Cultured and normal retinas showed similar
      relative expression levels of recoverin and rhodopsin mRNA. In cultured rat
      retina, the density of S-cones was high and M/L-cones could not be
      immunohistochemically detected. However, M/L-cone photoreceptor mRNA was
      detectable, but at a fourfold lower level in cultured than in vivo retinas. The S
      cone photoreceptor mRNA level was almost twofold lower than in vivo. Retinal
      pigment epithelium cells in cultured specimens showed no RPE65 immunolabeling,
      but expressed immunolabeling for ED-1 indicating phagocytic activity of these
      cells in vitro. CONCLUSIONS: We assume that the high density of S-cones and
      virtually no M/L-cones seen in in vitro retinas might represent an immature stage
      with numerous S-cones and suppressed transdifferentiation into M/L-cone
      phenotype. A non-functional relationship between photoreceptor cells and a
      dysfunctional retinal pigment epithelium may have severe consequences for the
      development of outer segments.

PMID- 14685148
TI  - Crosslinking of human lens 9 kDa gammaD-crystallin fragment in vitro and in vivo.
AB  - PURPOSE: [corrected] The aims of this study were to determine in vitro
      crosslinking of a 9 kDa gammaD-crystallin fragment alone and with alpha-, beta-,
      or gamma-crystallins, the existence of covalent multimers of the polypeptide in
      vivo, and posttranslational modifications in the three isoforms of the
      polypeptide. METHODS: A mixture of crystallin fragments (3-14 kDa), a 9 kDa
      gammaD-crystallin polypeptide or the polypeptide and individual alpha-, beta-, or
      gamma-crystallins, were incubated at 37 degrees C for a desired length of time
      and the crosslinked species were analyzed by sodium dodecylsulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE), size exclusion Agarose A 1.5 gel chromatography,
      and western blot analysis. In addition, the existence of covalent multimers of
      the 9 kDa polypeptide in human lens water soluble (WS) and water insoluble (WI)
      protein fractions of normal and cataractous human lenses was determined by
      western blot analyses. The posttranslationally modified amino acids of three
      isofroms of the polypeptide were identified by matrix assisted laser desorption
      ionization-time of flight (MALDI-TOF) and ES-MS/MS mass spectrometric analyses.
      RESULTS: Following incubation of a mixture of the crystallin fragments or the 9
      kDa polypeptide, covalently crosslinked species held via non-disulfide bonding
      were seen on SDS-PAGE analysis. The polypeptide also exhibited crosslinking with
      individual alpha-, beta-, and gamma-crystallins. After western blot analysis with
      site specific anti-9 kDa antibodies, both WS and WI protein fractions from normal
      and cataractous lenses showed immunoreactive 27 and 45 kDa multimers. The mass
      spectrometric analysis of the three isoforms of the polypeptide (with identical
      molecular weight but different charges) showed oxidized methionine and tryptophan
      residues, with the latter residue containing two oxygens. CONCLUSIONS: The data
      suggest that a 9 kDa gammaD-crystallin fragment demonstrated crosslinking
      properties, which might be due to oxidation of its methionine and tryptophan
      residues.

PMID- 14685149
TI  - Functional reconstruction of rabbit corneal epithelium by human limbal cells
      cultured on amniotic membrane.
AB  - PURPOSE: To investigate the phenotype of fetal and adult human limbal cells
      cultured on human amniotic membrane and the ability of cultured adult human
      limbal cells to repair limbal stem cell deficiency in a rabbit model. METHODS:
      Human adult and fetal limbal cells were isolated and cultured either on plastic
      plates or on human amniotic membrane. Connexin43, p63, and keratins 3 and 12 (K3
      and K12) were detected by immunofluorescence and RT-PCR. Limbal stem cell
      deficiency was established in rabbits using chemical ablation and mechanical
      debridement. Cultured adult human limbal cells were transplanted onto rabbit
      corneas one month after injury, then fixed and imbedded in paraffin forty days
      later. Immunofluorescent staining of human-nuclear antigen, p63, K3, and
      connexin43 identified human-specific cells, progenitor cells, and differentiated
      corneal epithelial cells, respectively. RESULTS: Adult and fetal cultured limbal
      cells appeared similar in morphology. RT-PCR results showed that cells cultured
      from the human adult and fetal limbal area expressed both p63 and K12, whereas
      cells from central adult epithelium expressed K12 only. Immunofluorescent
      staining showed that more cells were p63 positive when cultured on human amniotic
      membrane than on plastic. Double staining for p63 and connexin43 showed some p63
      positive cells co-expressing connexin43. After transplantation of adult human
      limbal cells cultured on human amniotic membrane, injured rabbit corneas were
      completely reconstructed exhibiting epithelial integrity, improved corneal
      clarity, and little or no neovascularization. The majority of repopulated
      epithelial cells expressed anti-human nuclear antibody. Cells expressing p63
      occurred throughout the new epithelium. CONCLUSIONS: During healing, expression
      of p63 is not limited to epithelial stem cells but may also mark transient
      amplifying progenitor cells. Culture on human amniotic membrane suppresses
      differentiation of limbal epithelial cells and promotes the proliferation of p63
      expressing cells. Amniotic membrane-cultured human limbal cells fully
      reconstructed rabbit corneas having limbal stem cell deficiency, with human cells
      providing most of the cells of the new epithelium. Expression p63 is distributed
      throughout the reconstructed tissue.

PMID- 14685150
TI  - FGF-2 induced reorganization and disruption of actin cytoskeleton through PI 3
      kinase, Rho, and Cdc42 in corneal endothelial cells.
AB  - PURPOSE: Corneal endothelial cells (CECs) undergo endothelial to mesenchymal
      transformation (EMT) in response to FGF-2 stimulation. One phenotypic change that
      occurs during EMT is a change in cell shape from polygonal to elongated
      fibroblast-like cells. We investigated whether FGF-2 plays a role in this
      morphogenetic pathway by reorganizing actin cytoskeleton through the actions of
      phosphatidylinositol (PI) 3-kinase and the Ras related Rho family of small
      guanosine triphosphatases (GTPases). METHODS: Cell morphology was analyzed using
      phase contrast microscopy, and the organization of actin cytoskeleton and focal
      adhesions were analyzed by immunofluorescent staining. Expression of vinculin and
      beta-actin was determined by immunoblot analysis. Pharmacologic inhibitors
      (LY294002, C3 exoenzyme, Y27632, or PD98059) or neutralizing antibody to FGF-2,
      respectively, were used to block PI 3-kinase, Rho, Rho associated kinase,
      extracellular signal regulated kinase, or FGF-2 pathways. RESULTS: CECs treated
      with FGF-2 became smaller and lost their characteristic polygonal cell
      morphology. Such cell shape change was completely blocked by treatment with
      LY294002. CECs in culture have abundant stress fibers that are oriented radially
      across the cell. However, FGF-2 caused a loss of these stress fibers and focal
      adhesions. The modulated cells contained a cortical actin ring while LY294002
      completely abolished this action of FGF-2 on actin cytoskeleton. Treatment of
      cells with C3 exoenzyme or Y27632 in the presence of FGF-2 induced spindle shaped
      cells with prominent pseudopodia which were rapidly formed upon exposure to the
      inhibitor. The expression level of vinculin was found to be similar in all
      experimental conditions but vinculin was mostly translocated to the cytoplasm in
      response to FGF-2 stimulation. CECs plated on Matrigel matrix demonstrated
      findings similar to those from cells plated on the conventional culture dishes,
      except that Matrigel facilitated the formation of pseudopodia. We further
      investigated in vivo actin organization using organ cultures of corneal
      endothelium (CE) on Descemet's membrane. The contact inhibited endothelial
      monolayer demonstrated a circumferential actin ring, and no stress fibers were
      observed. When CE was treated with FGF-2, a half population of CE lost its
      characteristic contact inhibited cobblestone morphology. Actin cortex was greatly
      disrupted in these modulated cells. Both neutralizing antibody to FGF-2 and
      LY294002 completely impeded the modulating activity of FGF-2 on the endothelial
      monolayer. When CE was simultaneously treated with FGF-2 and Y27632, the
      circumferential actin cortex was greatly disrupted and the endothelial monolayer
      was transformed into multi-layers of fibroblastic cells containing pseudopodia.
      Both LY294002 and neutralizing antibody to FGF-2 antagonized the actions of FGF-2
      and Y27632. CONCLUSIONS: These data indicate that CECs in culture have
      constitutively active Rho activity as evidenced by stress fiber formation and
      that PI 3-kinase negatively regulates the formation of stress fibers and focal
      adhesions, perhaps antagonizing the Rho pathways. Formation of pseudopodia in
      response to FGF-2 and Y27632 may suggest that the Rho/ROCK pathway negatively
      regulates Cdc42.

PMID- 14685151
TI  - Child and adolescent obesity.

PMID- 14685153
TI  - Prevalence of lysosomal storage diseases in Portugal.
AB  - Lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders
      individually considered as rare, and few data on its prevalence has been reported
      in the literature. The overall birth prevalence of the 29 different LSDs studied
      in the Portuguese population was calculated to be 25/100000 live births, twice
      the prevalence previously described in Australia and in The Netherlands. The
      comparison of the prevalence profile of the LSDs presenting a prevalence higher
      than 0.5/100000 in the Portuguese, Dutch and Australian populations showed, in
      the Portuguese, the existence of a higher prevalence of GM2 gangliosidoses (B
      variant), mucolipidoses (II and III), Niemman-Pick type C and metachromatic
      leukodystrophy (MLD), and a lower prevalence of Pompe and Fabry. The highest
      prevalence value for a single LSD is the one of GM2 gangliosidoses (B variant),
      corresponding to 3/100000, a value which is significantly higher than the
      prevalence of the most frequent LSD in Dutch, Pompe disease (2/100000) and
      Australians, Gaucher's disease (GD) (1.8/100000). It is worth noting that the
      highest prevalence of GM2 gangliosidoses found in the Portuguese is mainly due to
      the existence of a unique subtype, the rare juvenile B1 variant.

PMID- 14685154
TI  - A strategy for treatment of Epstein-Barr virus-positive Hodgkin's disease by
      targeting interleukin 12 to the tumor environment using tumor antigen-specific T
      cells.
AB  - Adoptive immunotherapy with Epstein-Barr virus (EBV)-specific cytotoxic T cells
      (CTL) is effective for the prophylaxis and treatment of EBV-induced lymphoma in
      hematopoietic stem cell recipients. However, in EBV-positive Hodgkin's disease
      (HD) the efficacy of adoptively transferred EBV-specific CTL may be limited by
      tumor-derived immunosuppressive factors, such as T-cell growth factor (TGF) beta,
      interleukin (IL)13 and the chemokine TARC. Local delivery of IL12 to tumor sites
      by tumor-specific CTL could provide direct antitumor effects and overcome the CTL
      inhibitory effects of the Th2 tumor environment while avoiding the systemic
      toxicity of recombinant IL12. EBV-specific CTL transduced with a retrovirus
      vector expressing the p40 and p35 subunits of IL12 as a single molecule (Flexi
      IL12), produced IL12 following antigenic stimulation. This resulted in an
      elevated production of Th1 cytokines, including interferon gamma and tumor
      necrosis factor alpha, and a reduction in the Th2 cytokines IL4 and IL5. Flexi
      IL12-transduced CTL resisted the antiproliferative and anticytotoxic effects of
      exogenous TGFbeta, likely by antagonizing the TGFbeta-induced downregulation of
      the Th1 transcriptional factor T-bet. In addition, Flexi-IL12-transduced CTL
      demonstrated a proliferative advantage in the presence of inhibitory supernatants
      from HD-derived cell lines. Tumor-specific, Flexi-IL12-transduced EBV-specific
      CTL should have a functional advantage over unmodified CTL, particularly in the
      presence of the adverse Th2 cytokine environment produced by Hodgkin tumor cells.

PMID- 14685155
TI  - DeltaNp73 stabilises TAp73 proteins but compromises their function due to
      inhibitory hetero-oligomer formation.

PMID- 14685156
TI  - A p38 inhibitor allows to dissociate differentiation and apoptotic processes
      triggered upon LIF withdrawal in mouse embryonic stem cells.
AB  - Mouse embryonic stem cells remain pluripotent when maintained in the presence of
      leukemia inhibitory factor (LIF). Upon LIF withdrawal, most cells differentiate
      into various lineages, while some die by apoptosis within 3 days. We have
      analyzed the activation pattern of the mitogen-activated protein kinase (MAPK)
      families and characterized the expression profile of selected genes modulated
      during differentiation or apoptosis. We show that p38 MAPKs are activated first,
      during the apoptotic crisis, while extracellular-regulated kinases and c-Jun N
      terminal kinases are induced after the apoptotic crisis in differentiated cells.
      However, by using both p38 kinase inhibitors (PD169316 and SB203580) and a
      p38alpha(-/-) cell line, we demonstrate that p38alpha activation is rather a
      consequence than a cause of apoptosis. We thus reveal novel properties of
      PD169316, which induces cell survival without impairing cell differentiation, and
      identify PD169316-sensitive targets like the fibroblast growth factor-5,
      Brachyury and bcl-2 genes. Finally, we demonstrate that overexpression of the
      PD169316 - regulated bcl-2 gene prevents LIF withdrawal - induced cell death.

PMID- 14685157
TI  - UV irradiation inhibits ABC transporters via generation of ADP-ribose by
      concerted action of poly(ADP-ribose) polymerase-1 and glycohydrolase.
AB  - ATP-binding cassette (ABC) transporters are involved in the transport of multiple
      substrates across cellular membranes, including metabolites, proteins, and drugs.
      Employing a functional fluorochrome export assay, we found that UVB irradiation
      strongly inhibits the activity of ABC transporters. Specific inhibitors of
      poly(ADP-ribose) polymerase-1 (PARP-1) restored the function of ABC transporters
      in UVB-irradiated cells, and PARP-1-deficient cells did not undergo UVB-induced
      membrane transport inhibition. These data suggest that PARP-1 activation is
      necessary for ABC transporter functional downregulation. The hydrolysis of
      poly(ADP-ribose) by poly(ADP-ribose) glycohydrolase (PARG) was also required,
      since specific PARG inhibitors, which limit the production of ADP-ribose
      molecules, restored the function of ABC transporters. Furthermore, ADP-ribose
      molecules potently inhibited the activity of the ABC transporter P-glycoprotein.
      Hence, poly(ADP-ribose) metabolism appears to play a novel role in the regulation
      of ABC transporters.

PMID- 14685158
TI  - JNK2 mediates TNF-induced cell death in mouse embryonic fibroblasts via
      regulation of both caspase and cathepsin protease pathways.
AB  - Recent studies strongly suggest an active involvement of the c-Jun N-terminal
      kinase (JNK) signaling pathway in tumor necrosis factor (TNF)-induced apoptosis.
      The direct evidence for the role of JNK and its isoforms has been missing and the
      mechanism of how JNK actually could facilitate this process has remained unclear.
      In this study, we show that Jnk2-/- primary mouse embryonic fibroblasts (pMEFs)
      exhibit resistance towards TNF-induced apoptosis as compared to corresponding
      wild-type and Jnk1-/- pMEFs. JNK2-deficient pMEFs could be resensitized to TNF
      via retroviral transduction of any of the four different JNK2 splicing variants.
      Jnk2-/- pMEFs displayed deficient and delayed effector caspase activation as well
      as impaired cytosolic cystein cathepsin activity: processes that both were needed
      for efficient TNF-induced apoptosis in pMEFs. Our work demonstrates that JNK has
      a central role in the promotion of TNF-induced apoptosis in pMEFs, and that the
      JNK2 isoform can regulate both mitochondrial and lysosomal death pathways in
      these cells.

PMID- 14685159
TI  - Do cells need CDK2 and ... Bcr-Abl?

PMID- 14685160
TI  - E2F1 deficiency impairs murine spermatogenesis and augments testicular
      degeneration in SCP3-nullizygous mice.

PMID- 14685161
TI  - Caspase-12: an overview.

PMID- 14685163
TI  - Roles of CHOP/GADD153 in endoplasmic reticulum stress.
AB  - Endoplasmic reticulum (ER) is the site of synthesis and folding of secretory
      proteins. Perturbations of ER homeostasis affect protein folding and cause ER
      stress. ER can sense the stress and respond to it through translational
      attenuation, upregulation of the genes for ER chaperones and related proteins,
      and degradation of unfolded proteins by a quality-control system. However, when
      the ER function is severely impaired, the organelle elicits apoptotic signals. ER
      stress has been implicated in a variety of common diseases such as diabetes,
      ischemia and neurodegenerative disorders. One of the components of the ER stress
      mediated apoptosis pathway is C/EBP homologous protein (CHOP), also known as
      growth arrest- and DNA damage-inducible gene 153 (GADD153). Here, we summarize
      the current understanding of the roles of CHOP/GADD153 in ER stress-mediated
      apoptosis and in diseases including diabetes, brain ischemia and
      neurodegenerative disease.

PMID- 14685162
TI  - Folic acid rescues nitric oxide-induced neural tube closure defects.

PMID- 14685164
TI  - Ca2+ homeostasis and apoptotic resistance of neuroendocrine-differentiated
      prostate cancer cells.
AB  - Neuroendocrine (NE) differentiation is a hallmark of advanced, androgen
      independent prostate cancer, for which there is no successful therapy. NE tumor
      cells are nonproliferating and escape apoptotic cell death; therefore, an
      understanding of the apoptotic status of the NE phenotype is imperative for the
      development of new therapies for prostate cancer. Here, we report for the first
      time on alterations in intracellular Ca(2+) homeostasis, which is a key factor in
      apoptosis, caused by NE differentiation of androgen-dependent prostate cancer
      epithelial cells. NE-differentiating regimens, either cAMP elevation or androgen
      deprivation, resulted in a reduced endoplasmic reticulum Ca(2+)-store content due
      to both SERCA 2b Ca(2+) ATPase and luminal Ca(2+) binding/storage chaperone
      calreticulin underexpression, and to a downregulated store-operated Ca(2+)
      current. NE-differentiated cells showed enhanced resistance to thapsigargin- and
      TNF-alpha-induced apoptosis, unrelated to antiapoptotic Bcl-2 protein
      overexpression. Our results suggest that targeting the key players determining
      Ca(2+) homeostasis in an attempt to enhance the proapoptotic potential of
      malignant cells may prove to be a useful strategy in the treatment of advanced
      prostate cancer.

PMID- 14685166
TI  - Ten years of publication in cell death.

PMID- 14685167
TI  - Of sea urchins and worms: development and cancer.

PMID- 14685168
TI  - Death and more: DNA damage response pathways in the nematode C. elegans.
AB  - Genotoxic stress is a threat to our cells' genome integrity. Failure to repair
      DNA lesions properly after the induction of cell proliferation arrest can lead to
      mutations or large-scale genomic instability. Because such changes may have
      tumorigenic potential, damaged cells are often eliminated via apoptosis. Loss of
      this apoptotic response is actually one of the hallmarks of cancer. Towards the
      effort to elucidate the DNA damage-induced signaling steps leading to these
      biological events, an easily accessible model system is required, where the
      acquired knowledge can reveal the mechanisms underlying more complex organisms.
      Accumulating evidence coming from studies in Caenorhabditis elegans point to its
      usefulness as such. In the worm's germline, DNA damage can induce both cell cycle
      arrest and apoptosis, two responses that are spatially separated. The latter is a
      tightly controlled process that is genetically indistinguishable from
      developmental programmed cell death. Upstream of the central death machinery,
      components of the DNA damage signaling cascade lie and act either as sensors of
      the lesion or as transducers of the initial signal detected. This review
      summarizes the findings of several studies that specify the elements of the DNA
      damage-induced responses, as components of the cell cycle control machinery, the
      repairing process or the apoptotic outcome. The validity of C. elegans as a tool
      to further dissect the complex signaling network of these responses and the high
      potential for it to reveal important links to cancer and other genetic
      abnormalities are addressed.

PMID- 14685170
TI  - Met, metastasis, motility and more.

PMID- 14685171
TI  - Syndecans: proteoglycan regulators of cell-surface microdomains?

PMID- 14685172
TI  - Post-translational modifications regulate microtubule function.

PMID- 14685173
TI  - Getting to the end: telomerase access in yeast and humans.

PMID- 14685174
TI  - Splicing double: insights from the second spliceosome.

PMID- 14685175
TI  - The centennial of the Cajal body.

PMID- 14685176
TI  - Secrecy damages the NIH.

PMID- 14685177
TI  - Variation for all.

PMID- 14685178
TI  - Accusations of bias prompt NIH review of ethical guidelines.

PMID- 14685179
TI  - Scientists attack industrial influence.

PMID- 14685180
TI  - Disillusionment and doubt undermine Kyoto's birthday bash.

PMID- 14685181
TI  - 'Reverse genetics' could offer forward-thinking flu vaccine.

PMID- 14685182
TI  - Koreans rustle up madness-resistant cows.

PMID- 14685183
TI  - EMBO chief threatens to quit over funding crisis.

PMID- 14685184
TI  - Coral reveals ancient origins of human genes.

PMID- 14685185
TI  - Elsevier waves goodbye to BioMedNet web portal.

PMID- 14685187
TI  - Climate of conflict: in the shadow of war.

PMID- 14685189
TI  - Nanotechnology: what is there to fear from something so small?

PMID- 14685190
TI  - Genomics: compare and contrast.

PMID- 14685191
TI  - Cosmology: welcome to the real world.

PMID- 14685192
TI  - China: from SARS to the stars.

PMID- 14685194
TI  - Developing-world health: the fightback starts here.

PMID- 14685195
TI  - NASA: trawling through the wreckage.

PMID- 14685197
TI  - Membrane proteins: channel voyager makes waves.

PMID- 14685198
TI  - Climate change: the long road from Kyoto.

PMID- 14685199
TI  - Neuroscience: genomics on the brain.

PMID- 14685201
TI  - Celebrating 50 years of the cell cycle.

PMID- 14685202
TI  - What Darwin knew.

PMID- 14685203
TI  - There's more to science (and life) than scoops.

PMID- 14685204
TI  - 1904 and all that.

PMID- 14685210
TI  - Gaia: the living Earth.

PMID- 14685213
TI  - Archaeology: art of the ancients.

PMID- 14685214
TI  - Cell biology: earthworms and lipid couriers.

PMID- 14685215
TI  - Organic chemistry: aromatics do the twist.

PMID- 14685216
TI  - Biomechanics: early birds surmount steep slopes.

PMID- 14685217
TI  - Planetary science: icy martian mysteries.

PMID- 14685218
TI  - Cell cycle: passenger acrobatics.

PMID- 14685219
TI  - Astronomy: wide-angle lens.

PMID- 14685222
TI  - Physiology: efficiency of equine express postal systems.

PMID- 14685223
TI  - Structural colour: opal analogue discovered in a weevil.

PMID- 14685224
TI  - Plasma antioxidants: health benefits of eating chocolate?

PMID- 14685225
TI  - Nutrition: milk and absorption of dietary flavanols.

PMID- 14685227
TI  - The International HapMap Project.
AB  - The goal of the International HapMap Project is to determine the common patterns
      of DNA sequence variation in the human genome and to make this information freely
      available in the public domain. An international consortium is developing a map
      of these patterns across the genome by determining the genotypes of one million
      or more sequence variants, their frequencies and the degree of association
      between them, in DNA samples from populations with ancestry from parts of Africa,
      Asia and Europe. The HapMap will allow the discovery of sequence variants that
      affect common disease, will facilitate development of diagnostic tools, and will
      enhance our ability to choose targets for therapeutic intervention.

PMID- 14685228
TI  - Recent ice ages on Mars.
AB  - A key pacemaker of ice ages on the Earth is climatic forcing due to variations in
      planetary orbital parameters. Recent Mars exploration has revealed dusty, water
      ice-rich mantling deposits that are layered, metres thick and latitude dependent,
      occurring in both hemispheres from mid-latitudes to the poles. Here we show
      evidence that these deposits formed during a geologically recent ice age that
      occurred from about 2.1 to 0.4 Myr ago. The deposits were emplaced symmetrically
      down to latitudes of approximately 30 degrees--equivalent to Saudi Arabia and the
      southern United States on the Earth--in response to the changing stability of
      water ice and dust during variations in obliquity (the angle between Mars' pole
      of rotation and the ecliptic plane) reaching 30-35 degrees. Mars is at present in
      an 'interglacial' period, and the ice-rich deposits are undergoing reworking,
      degradation and retreat in response to the current instability of near-surface
      ice. Unlike the Earth, martian ice ages are characterized by warmer polar
      climates and enhanced equatorward transport of atmospheric water and dust to
      produce widespread smooth deposits down to mid-latitudes.

PMID- 14685229
TI  - Molecular machinery for non-vesicular trafficking of ceramide.
AB  - Synthesis and sorting of lipids are essential for membrane biogenesis; however,
      the mechanisms underlying the transport of membrane lipids remain little
      understood. Ceramide is synthesized at the endoplasmic reticulum and translocated
      to the Golgi compartment for conversion to sphingomyelin. The main pathway of
      ceramide transport to the Golgi is genetically impaired in a mammalian mutant
      cell line, LY-A. Here we identify CERT as the factor defective in LY-A cells.
      CERT, which is identical to a splicing variant of Goodpasture antigen-binding
      protein, is a cytoplasmic protein with a phosphatidylinositol-4-monophosphate
      binding (PtdIns4P) domain and a putative domain for catalysing lipid transfer. In
      vitro assays show that this lipid-transfer-catalysing domain specifically
      extracts ceramide from phospholipid bilayers. CERT expressed in LY-A cells has an
      amino acid substitution that destroys its PtdIns4P-binding activity, thereby
      impairing its Golgi-targeting function. We conclude that CERT mediates the
      intracellular trafficking of ceramide in a non-vesicular manner.

PMID- 14685230
TI  - A gravitationally lensed quasar with quadruple images separated by 14.62
      arcseconds.
AB  - Gravitational lensing is a powerful tool for the study of the distribution of
      dark matter in the Universe. The cold-dark-matter model of the formation of large
      scale structures (that is, clusters of galaxies and even larger assemblies)
      predicts the existence of quasars gravitationally lensed by concentrations of
      dark matter so massive that the quasar images would be split by over 7 arcsec.
      Numerous searches for large-separation lensed quasars have, however, been
      unsuccessful. All of the roughly 70 lensed quasars known, including the first
      lensed quasar discovered, have smaller separations that can be explained in terms
      of galaxy-scale concentrations of baryonic matter. Although gravitationally
      lensed galaxies with large separations are known, quasars are more useful
      cosmological probes because of the simplicity of the resulting lens systems. Here
      we report the discovery of a lensed quasar, SDSS J1004 + 4112, which has a
      maximum separation between the components of 14.62 arcsec. Such a large
      separation means that the lensing object must be dominated by dark matter. Our
      results are fully consistent with theoretical expectations based on the cold-dark
      matter model.

PMID- 14685231
TI  - Subatomic movements of a domain wall in the Peierls potential.
AB  - The discrete nature of crystal lattices plays a role in virtually every material
      property. But it is only when the size of entities hosted by a crystal becomes
      comparable to the lattice period--as occurs for dislocations, vortices in
      superconductors and domain walls--that this discreteness is manifest explicitly.
      The associated phenomena are usually described in terms of a background Peierls
      'atomic washboard' energy potential, which was first introduced for the case of
      dislocation motion in the 1940s. This concept has subsequently been invoked in
      many situations to describe certain features in the bulk behaviour of materials,
      but has to date eluded direct detection and experimental scrutiny at a
      microscopic level. Here we report observations of the motion of a single magnetic
      domain wall at the scale of the individual peaks and troughs of the atomic energy
      landscape. Our experiments reveal that domain walls can become trapped between
      crystalline planes, and that they propagate by distinct jumps that match the
      lattice periodicity. The jumps between valleys are found to involve unusual
      dynamics that shed light on the microscopic processes underlying domain-wall
      propagation. Such observations offer a means for probing experimentally the
      physics of topological defects in discrete lattices--a field rich in phenomena
      that have been subject to extensive theoretical study.

PMID- 14685232
TI  - Subwavelength-diameter silica wires for low-loss optical wave guiding.
AB  - Silica waveguides with diameters larger than the wavelength of transmitted light
      are widely used in optical communications, sensors and other applications.
      Minimizing the width of the waveguides is desirable for photonic device
      applications, but the fabrication of low-loss optical waveguides with
      subwavelength diameters remains challenging because of strict requirements on
      surface roughness and diameter uniformity. Here we report the fabrication of
      subwavelength-diameter silica 'wires' for use as low-loss optical waveguides
      within the visible to near-infrared spectral range. We use a two-step drawing
      process to fabricate long free-standing silica wires with diameters down to 50 nm
      that show surface smoothness at the atomic level together with uniformity of
      diameter. Light can be launched into these wires by optical evanescent coupling.
      The wires allow single-mode operation, and have an optical loss of less than 0.1
      dB mm(-1). We believe that these wires provide promising building blocks for
      future microphotonic devices with subwavelength-width structures.

PMID- 14685233
TI  - Synthesis of a Mobius aromatic hydrocarbon.
AB  - The defining feature of aromatic hydrocarbon compounds is a cyclic molecular
      structure stabilized by the delocalization of pi electrons that, according to the
      Huckel rule, need to total 4n + 2 (n = 1,2, em leader ); cyclic compounds with 4n
      pi electrons are antiaromatic and unstable. But in 1964, Heilbronner predicted on
      purely theoretical grounds that cyclic molecules with the topology of a Mobius
      band--a ring constructed by joining the ends of a rectangular strip after having
      given one end half a twist--should be aromatic if they contain 4n, rather than 4n
      + 2, pi electrons. The prediction stimulated attempts to synthesize Mobius
      aromatic hydrocarbons, but twisted cyclic molecules are destabilized by large
      ring strains, with the twist also suppressing overlap of the p orbitals involved
      in electron delocalization and stabilization. In larger cyclic molecules, ring
      strain is less pronounced but the structures are very flexible and flip back to
      the less-strained Huckel topology. Although transition-state species, an unstable
      intermediate and a non-conjugated cyclic molecule, all with a Mobius topology,
      have been documented, a stable aromatic Mobius system has not yet been realized.
      Here we report that combining a 'normal' aromatic structure (with p orbitals
      orthogonal to the ring plane) and a 'belt-like' aromatic structure (with p
      orbitals within the ring plane) yields a Mobius compound stabilized by its
      extended pi system.

PMID- 14685234
TI  - Stable isotopic evidence for methane seeps in Neoproterozoic postglacial cap
      carbonates.
AB  - The Earth's most severe glaciations are thought to have occurred about 600
      million years ago, in the late Neoproterozoic era. A puzzling feature of glacial
      deposits from this interval is that they are overlain by 1-5-m-thick 'cap
      carbonates' (particulate deep-water marine carbonate rocks) associated with a
      prominent negative carbon isotope excursion. Cap carbonates have been
      controversially ascribed to the aftermath of almost complete shutdown of the
      ocean ecosystems for millions of years during such ice ages--the 'snowball Earth'
      hypothesis. Conversely, it has also been suggested that these carbonate rocks
      were the result of destabilization of methane hydrates during deglaciation and
      concomitant flooding of continental shelves and interior basins. The most
      compelling criticism of the latter 'methane hydrate' hypothesis has been the
      apparent lack of extreme isotopic variation in cap carbonates inferred locally to
      be associated with methane seeps. Here we report carbon isotopic and petrographic
      data from a Neoproterozoic postglacial cap carbonate in south China that provide
      direct evidence for methane-influenced processes during deglaciation. This
      evidence lends strong support to the hypothesis that methane hydrate
      destabilization contributed to the enigmatic cap carbonate deposition and
      strongly negative carbon isotopic anomalies following Neoproterozoic ice ages.
      This explanation requires less extreme environmental disturbance than that
      implied by the snowball Earth hypothesis.

PMID- 14685235
TI  - A change in the freshwater balance of the Atlantic Ocean over the past four
      decades.
AB  - The oceans are a global reservoir and redistribution agent for several important
      constituents of the Earth's climate system, among them heat, fresh water and
      carbon dioxide. Whereas these constituents are actively exchanged with the
      atmosphere, salt is a component that is approximately conserved in the ocean. The
      distribution of salinity in the ocean is widely measured, and can therefore be
      used to diagnose rates of surface freshwater fluxes, freshwater transport and
      local ocean mixing--important components of climate dynamics. Here we present a
      comparison of salinities on a long transect (50 degrees S to 60 degrees N)
      through the western basins of the Atlantic Ocean between the 1950s and the 1990s.
      We find systematic freshening at both poleward ends contrasted with large
      increases of salinity pervading the upper water column at low latitudes. Our
      results extend a growing body of evidence indicating that shifts in the oceanic
      distribution of fresh and saline waters are occurring worldwide in ways that
      suggest links to global warming and possible changes in the hydrologic cycle of
      the Earth.

PMID- 14685236
TI  - Palaeolithic ivory sculptures from southwestern Germany and the origins of
      figurative art.
AB  - Archaeologists have always viewed the origin of figurative art as a crucial
      threshold in human evolution. Here I report the discovery of three figurines
      carved from mammoth ivory at Hohle Fels Cave in the Swabian Jura of southwestern
      Germany, which provides new evidence for the appearance of figurative art more
      than 30,000 years ago. The finds include the oldest known representation of a
      bird, a therianthropic sculpture and an animal that most closely resembles a
      horse. The Aurignacian sculptures of the Swabian Jura belong to one of the oldest
      traditions of figurative art known worldwide and point to the Upper Danube as an
      important centre of cultural innovation during the early Upper Palaeolithic
      period.

PMID- 14685237
TI  - A larval Devonian lungfish.
AB  - Perhaps the most enduring of puzzles in palaeontology has been the identity of
      Palaeospondylus gunni Traquair, a tiny (5-60-mm) vertebrate fossil from the
      Middle Devonian period (approximately 385 Myr ago) of Scotland, first discovered
      in 1890 (refs 1-3). It is known principally from a single site (Achanarras
      Quarry, Caithness) where, paradoxically, it is extremely abundant, preserved in
      varved lacustrine deposits along with 13 other genera of fishes. Here we show
      that Palaeospondylus is the larval stage of a lungfish, most probably Dipterus
      valenciennesi Sedgwick and Murchison 1828 (ref. 5), and that development of the
      adult form requires a distinct metamorphosis. Palaeospondylus is the oldest known
      true larva of a vertebrate.

PMID- 14685238
TI  - Predicting distributions of known and unknown reptile species in Madagascar.
AB  - Despite the importance of tropical biodiversity, informative species
      distributional data are seldom available for biogeographical study or setting
      conservation priorities. Modelling ecological niche distributions of species
      offers a potential solution; however, the utility of old locality data from
      museums, and of more recent remotely sensed satellite data, remains poorly
      explored, especially for rapidly changing tropical landscapes. Using 29 modern
      data sets of environmental land coverage and 621 chameleon occurrence localities
      from Madagascar (historical and recent), here we demonstrate a significant
      ability of our niche models in predicting species distribution. At 11 recently
      inventoried sites, highest predictive success (85.1%) was obtained for models
      based only on modern occurrence data (74.7% and 82.8% predictive success,
      respectively, for pre-1978 and all data combined). Notably, these models also
      identified three intersecting areas of over-prediction that recently yielded
      seven chameleon species new to science. We conclude that ecological niche
      modelling using recent locality records and readily available environmental
      coverage data provides informative biogeographical data for poorly known tropical
      landscapes, and offers innovative potential for the discovery of unknown
      distributional areas and unknown species.

PMID- 14685239
TI  - Presynaptic induction of heterosynaptic associative plasticity in the mammalian
      brain.
AB  - The induction of associative synaptic plasticity in the mammalian central nervous
      system classically depends on coincident presynaptic and postsynaptic activity.
      According to this principle, associative homosynaptic long-term potentiation
      (LTP) of excitatory synaptic transmission can be induced only if synaptic release
      occurs during postsynaptic depolarization. In contrast, heterosynaptic plasticity
      in mammals is considered to rely on activity-independent, non-associative
      processes. Here we describe a novel mechanism underlying the induction of
      associative LTP in the lateral amygdala (LA). Simultaneous activation of
      converging cortical and thalamic afferents specifically induced associative, N
      methyl-D-aspartate (NMDA)-receptor-dependent LTP at cortical, but not at
      thalamic, inputs. Surprisingly, the induction of associative LTP at cortical
      inputs was completely independent of postsynaptic activity, including
      depolarization, postsynaptic NMDA receptor activation or an increase in
      postsynaptic Ca2+ concentration, and did not require network activity. LTP
      expression was mediated by a persistent increase in the presynaptic probability
      of release at cortical afferents. Our study shows the presynaptic induction and
      expression of heterosynaptic and associative synaptic plasticity on simultaneous
      activity of converging afferents. Our data indicate that input specificity of
      associative LTP can be determined exclusively by presynaptic properties.

PMID- 14685240
TI  - A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans.
AB  - How left/right functional asymmetry is layered on top of an anatomically
      symmetrical nervous system is poorly understood. In the nematode Caenorhabditis
      elegans, two morphologically bilateral taste receptor neurons, ASE left (ASEL)
      and ASE right (ASER), display a left/right asymmetrical expression pattern of
      putative chemoreceptor genes that correlates with a diversification of
      chemosensory specificities. Here we show that a previously undefined microRNA
      termed lsy-6 controls this neuronal left/right asymmetry of chemosensory receptor
      expression. lsy-6 mutants that we retrieved from a genetic screen for defects in
      neuronal left/right asymmetry display a loss of the ASEL-specific chemoreceptor
      expression profile with a concomitant gain of the ASER-specific profile. A lsy-6
      reporter gene construct is expressed in less than ten neurons including ASEL, but
      not ASER. lsy-6 exerts its effects on ASEL through repression of cog-1, an Nkx
      type homeobox gene, which contains a lsy-6 complementary site in its 3'
      untranslated region and that has been shown to control ASE-specific chemoreceptor
      expression profiles. lsy-6 is the first microRNA to our knowledge with a role in
      neuronal patterning, providing new insights into left/right axis formation.

PMID- 14685241
TI  - A self-organizing system of repressor gradients establishes segmental complexity
      in Drosophila.
AB  - Gradients of regulatory factors are essential for establishing precise patterns
      of gene expression during development; however, it is not clear how patterning
      information in multiple gradients is integrated to generate complex body plans.
      Here we show that opposing gradients of two Drosophila transcriptional
      repressors, Hunchback (Hb) and Knirps (Kni), position several segments by
      differentially repressing two distinct regulatory regions (enhancers) of the pair
      rule gene even-skipped (eve). Computational and in vivo analyses suggest that
      enhancer sensitivity to repression is controlled by the number and affinity of
      repressor-binding sites. Because the kni expression domain is positioned between
      two gradients of Hb, each enhancer directs expression of a pair of symmetrical
      stripes, one on each side of the kni domain. Thus, only two enhancers are
      required for the precise positioning of eight stripe borders (four stripes), or
      more than half of the whole eve pattern. Our results show that complex
      developmental expression patterns can be generated by simple repressor gradients.
      They also support the utility of computational analyses for defining and
      deciphering regulatory information contained in genomic DNA.

PMID- 14685243
TI  - Evolutionary conservation of biogenesis of beta-barrel membrane proteins.
AB  - The outer membranes of mitochondria and chloroplasts are distinguished by the
      presence of beta-barrel membrane proteins. The outer membrane of Gram-negative
      bacteria also harbours beta-barrel proteins. In mitochondria these proteins
      fulfil a variety of functions such as transport of small molecules (porin/VDAC),
      translocation of proteins (Tom40) and regulation of mitochondrial morphology
      (Mdm10). These proteins are encoded by the nucleus, synthesized in the cytosol,
      targeted to mitochondria as chaperone-bound species, recognized by the
      translocase of the outer membrane, and then inserted into the outer membrane
      where they assemble into functional oligomers. Whereas some knowledge has been
      accumulated on the pathways of insertion of proteins that span cellular membranes
      with alpha-helical segments, very little is known about how beta-barrel proteins
      are integrated into lipid bilayers and assembled into oligomeric structures. Here
      we describe a protein complex that is essential for the topogenesis of
      mitochondrial outer membrane beta-barrel proteins (TOB). We present evidence that
      important elements of the topogenesis of beta-barrel membrane proteins have been
      conserved during the evolution of mitochondria from endosymbiotic bacterial
      ancestors.

PMID- 14685242
TI  - The gene product Murr1 restricts HIV-1 replication in resting CD4+ lymphocytes.
AB  - Although human immunodeficiency virus-1 (HIV-1) infects quiescent and
      proliferating CD4+ lymphocytes, the virus replicates poorly in resting T cells.
      Factors that block viral replication in these cells might help to prolong the
      asymptomatic phase of HIV infection; however, the molecular mechanisms that
      control this process are not fully understood. Here we show that Murr1, a gene
      product known previously for its involvement in copper regulation, inhibits HIV-1
      growth in unstimulated CD4+ T cells. This inhibition was mediated in part through
      its ability to inhibit basal and cytokine-stimulated nuclear factor (NF)-kappaB
      activity. Knockdown of Murr1 increased NF-kappaB activity and decreased IkappaB
      alpha concentrations by facilitating phospho-IkappaB-alpha degradation by the
      proteasome. Murr1 was detected in CD4+ T cells, and RNA-mediated interference of
      Murr1 in primary resting CD4+ lymphocytes increased HIV-1 replication. Through
      its effects on the proteasome, Murr1 acts as a genetic restriction factor that
      inhibits HIV-1 replication in lymphocytes, which could contribute to the
      regulation of asymptomatic HIV infection and the progression of AIDS.

PMID- 14685244
TI  - An ABC transporter with a secondary-active multidrug translocator domain.
AB  - Multidrug resistance, by which cells become resistant to multiple unrelated
      pharmaceuticals, is due to the extrusion of drugs from the cell's interior by
      active transporters such as the human multidrug resistance P-glycoprotein. Two
      major classes of transporters mediate this extrusion. Primary-active transporters
      are dependent on ATP hydrolysis, whereas secondary-active transporters are driven
      by electrochemical ion gradients that exist across the plasma membrane. The ATP
      binding cassette (ABC) transporter LmrA is a primary drug transporter in
      Lactococcus lactis that can functionally substitute for P-glycoprotein in lung
      fibroblast cells. Here we have engineered a truncated LmrA protein that lacks the
      ATP-binding domain. Surprisingly, this truncated protein mediates a proton
      ethidium symport reaction without the requirement for ATP. In other words, it
      functions as a secondary-active multidrug uptake system. These findings suggest
      that the evolutionary precursor of LmrA was a secondary-active substrate
      translocator that acquired an ATP-binding domain to enable primary-active
      multidrug efflux in L. lactis.

PMID- 14685245
TI  - The Bloom's syndrome helicase suppresses crossing over during homologous
      recombination.
AB  - Mutations in BLM, which encodes a RecQ helicase, give rise to Bloom's syndrome, a
      disorder associated with cancer predisposition and genomic instability. A
      defining feature of Bloom's syndrome is an elevated frequency of sister chromatid
      exchanges. These arise from crossing over of chromatid arms during homologous
      recombination, a ubiquitous process that exists to repair DNA double-stranded
      breaks and damaged replication forks. Whereas crossing over is required in
      meiosis, in mitotic cells it can be associated with detrimental loss of
      heterozygosity. BLM forms an evolutionarily conserved complex with human
      topoisomerase IIIalpha (hTOPO IIIalpha), which can break and rejoin DNA to alter
      its topology. Inactivation of homologues of either protein leads to hyper
      recombination in unicellular organisms. Here, we show that BLM and hTOPO IIIalpha
      together effect the resolution of a recombination intermediate containing a
      double Holliday junction. The mechanism, which we term double-junction
      dissolution, is distinct from classical Holliday junction resolution and prevents
      exchange of flanking sequences. Loss of such an activity explains many of the
      cellular phenotypes of Bloom's syndrome. These results have wider implications
      for our understanding of the process of homologous recombination and the
      mechanisms that exist to prevent tumorigenesis.

PMID- 14685246
TI  - A conspicuous nickel protein in microbial mats that oxidize methane
      anaerobically.
AB  - Anaerobic oxidation of methane (AOM) in marine sediments is an important
      microbial process in the global carbon cycle and in control of greenhouse gas
      emission. The responsible organisms supposedly reverse the reactions of
      methanogenesis, but cultures providing biochemical proof of this have not been
      isolated. Here we searched for AOM-associated cell components in microbial mats
      from anoxic methane seeps in the Black Sea. These mats catalyse AOM rather than
      carry out methanogenesis. We extracted a prominent nickel compound displaying the
      same absorption spectrum as the nickel cofactor F430 of methyl-coenzyme M
      reductase, the terminal enzyme of methanogenesis; however, the nickel compound
      exhibited a higher molecular mass than F430. The apparent variant of F(430) was
      part of an abundant protein that was purified from the mat and that consists of
      three different subunits. Determined amino-terminal amino acid sequences matched
      a gene locus cloned from the mat. Sequence analyses revealed similarities to
      methyl-coenzyme M reductase from methanogenic archaea. The abundance of the
      nickel protein (7% of extracted proteins) in the mat suggests an important role
      in AOM.

PMID- 14685248
TI  - Protein folding and misfolding.
AB  - The manner in which a newly synthesized chain of amino acids transforms itself
      into a perfectly folded protein depends both on the intrinsic properties of the
      amino-acid sequence and on multiple contributing influences from the crowded
      cellular milieu. Folding and unfolding are crucial ways of regulating biological
      activity and targeting proteins to different cellular locations. Aggregation of
      misfolded proteins that escape the cellular quality-control mechanisms is a
      common feature of a wide range of highly debilitating and increasingly prevalent
      diseases.

PMID- 14685249
TI  - Quality control in the endoplasmic reticulum protein factory.
AB  - The endoplasmic reticulum (ER) is a factory where secretory proteins are
      manufactured, and where stringent quality-control systems ensure that only
      correctly folded proteins are sent to their final destinations. The changing
      needs of the ER factory are monitored by integrated signalling pathways that
      constantly adjust the levels of folding assistants. ER chaperones and signalling
      molecules are emerging as drug targets in amyloidoses and other protein
      conformational diseases.

PMID- 14685250
TI  - Protein degradation and protection against misfolded or damaged proteins.
AB  - The ultimate mechanism that cells use to ensure the quality of intracellular
      proteins is the selective destruction of misfolded or damaged polypeptides. In
      eukaryotic cells, the large ATP-dependent proteolytic machine, the 26S
      proteasome, prevents the accumulation of non-functional, potentially toxic
      proteins. This process is of particular importance in protecting cells against
      harsh conditions (for example, heat shock or oxidative stress) and in a variety
      of diseases (for example, cystic fibrosis and the major neurodegenerative
      diseases). A full understanding of the pathogenesis of the protein-folding
      diseases will require greater knowledge of how misfolded proteins are recognized
      and selectively degraded.

PMID- 14685251
TI  - Folding proteins in fatal ways.
AB  - Human diseases characterized by insoluble extracellular deposits of proteins have
      been recognized for almost two centuries. Such amyloidoses were once thought to
      represent arcane secondary phenomena of questionable pathogenic significance. But
      it is has now become clear that many different proteins can misfold and form
      extracellular or intracellular aggregates that initiate profound cellular
      dysfunction. Particularly challenging examples of such disorders occur in the
      post-mitotic environment of the neuron and include Alzheimer's and Parkinson's
      diseases. Understanding some of the principles of protein folding has helped to
      explain how such diseases arise, with attendant therapeutic insights.

PMID- 14685252
TI  - Therapeutic approaches to protein-misfolding diseases.
AB  - Several sporadic and genetic diseases are caused by protein misfolding. These
      include cystic fibrosis and other devastating diseases of childhood as well as
      Alzheimer's, Parkinson's and other debilitating maladies of the elderly. A
      unified view of the molecular and cellular pathogenesis of these conditions has
      led to the search for chemical chaperones that can slow, arrest or revert disease
      progression. Molecules are now emerging that link our biophysical insights with
      our therapeutic aspirations.

PMID- 14685253
TI  - Conference management.

PMID- 14685254
TI  - Microphthalmia transcription factor and NKI/C3 expression in cellular
      neurothekeoma.
AB  - While the usual or myxoid-type neurothekeoma has been reasonably well established
      as being a tumor of neural origin, the cellular neurothekeoma remains in disputed
      histogenesis. We studied a series of 11 cellular neurothekeomas using paraffin
      immunoperoxidase staining with microphthalmia transcription factor (Mitf),
      NKI/C3, and S-100. The majority of the tumors in our series stained with NKI/C3
      (9/11) and Mitf (9/11). All failed to stain with S-100. Furthermore, we divided
      our series of cellular neurothekeomas according to cytomorphology; tumors
      demonstrating predominantly spindled morphology, predominantly epithelioid
      morphology, and mixed spindle and epithelioid morphology. The two tumors that
      failed to stain with NKI/C3 both demonstrated predominantly spindled morphology.
      One of the tumors that failed to stain with Mitf showed exclusive spindled
      morphology, while the other showed mixed morphology (spindle and epithelioid).
      Two of the tumors, which stained strongly with Mitf, however, showed exclusive
      epithelioid morphology. This current study furthers the concept that cellular
      neurothekeoma is a tumor of neuroectodermal origin, and further suggests that it
      may express some component of melanocytic differentiation.

PMID- 14685255
TI  - Minichromosome maintenance protein in myxofibrosarcoma.
AB  - Histopathological assessment of myxofibrosarcoma may be difficult, especially on
      the basis of a small core biopsy, which enables only a crude evaluation of grade
      and prognosis. We have tested the hypothesis that determination of cell cycle
      state may assist in the diagnostic assessment of myxofibrosarcoma. We have
      studied 51 cases of high-grade (n=20), intermediate-grade (n=21), and low-grade
      (n=10) myxofibrosarcomas, as well as nine cases of benign myxoma. Cell cycle
      state within tumors was determined by immunostaining for the recently described
      marker minichromosome maintenance protein 2 (MCM2), together with Ki67. Labelling
      indices for both markers were correlated with tumor grade, mitotic index, and
      time to first recurrence. The MCM2 labelling indices were significantly higher
      than the Ki-67 labelling indices. Both indices showed a significant correlation
      with the mitotic index and both showed significant increases with increasing
      grade of myxofibrosarcoma. The MCM2 labelling index (but not the Ki67 labelling
      index) showed a significant inverse exponential correlation with the time to
      first recurrence. Myxoid and cellular areas showed no difference in the MCM2 and
      Ki-67 labeling index, suggesting that clinically useful information could be
      obtained from any component of a myxofibrosarcoma sampled in a needle biopsy
      and/or cytological specimen. We therefore suggest that assessment of cell cycle
      state may be a useful diagnostic adjunct in the histopathological assessment of
      myxofibrosarcoma, by enabling more accurate determination of grade and prediction
      of outcome.

PMID- 14685256
TI  - Intraneural synovial sarcoma: two cases.
AB  - We report two cases of intraneural synovial sarcoma. The first patient is a 46
      year-old female who presented for several months with soft-tissue mass in the
      right infra-auricular region. The second patient is a 11-year-old girl who fell
      and then presented with pain in the area innervated by the right C7 spinal root
      and a nodule identified in the nerve root foramina. Both lesions were of small
      size and presented with features of synovial sarcoma. A biphasic variant was
      found in case 1 and a monophasic variant was present in case 2.
      Immunohistochemical studies were performed to confirm the diagnosis, excluding
      the main differential diagnoses, namely schwannoma and malignant peripheral nerve
      sheath tumor. Ultrastructural study was performed in case 2 allowing exclusion of
      other possible diagnoses. Molecular studies were performed on paraffin-embedded
      tissue in both cases and revealed the known characteristic t(X;18)(SYT-SSX)
      translocation.

PMID- 14685257
TI  - Structural basis of ligand recognition by PABC, a highly specific peptide-binding
      domain found in poly(A)-binding protein and a HECT ubiquitin ligase.
AB  - The C-terminal domain of poly(A)-binding protein (PABC) is a peptide-binding
      domain found in poly(A)-binding proteins (PABPs) and a HECT (homologous to E6-AP
      C-terminus) family E3 ubiquitin ligase. In protein synthesis, the PABC domain of
      PABP functions to recruit several translation factors possessing the PABP
      interacting motif 2 (PAM2) to the mRNA poly(A) tail. We have determined the
      solution structure of the human PABC domain in complex with two peptides from
      PABP-interacting protein-1 (Paip1) and Paip2. The structures show a novel mode of
      peptide recognition, in which the peptide binds as a pair of beta-turns with
      extensive hydrophobic, electrostatic and aromatic stacking interactions.
      Mutagenesis of PABC and peptide residues was used to identify key protein-peptide
      interactions and quantified by isothermal calorimetry, surface plasmon resonance
      and GST pull-down assays. The results provide insight into the specificity of
      PABC in mediating PABP-protein interactions.

PMID- 14685258
TI  - What kinesin does at roadblocks: the coordination mechanism for molecular
      walking.
AB  - Competing models for the coordination of processive stepping in kinesin can be
      tested by introducing a roadblock to prevent lead head attachment. We used T93N,
      an irreversibly binding mutant monomer, as a roadblock, and measured the rates of
      nucleotide-induced detachment of kinesin monomers or dimers with and without the
      T93N roadblock using microflash photolysis combined with stopped flow. Control
      nucleotide-induced monomer (rK340) unbinding was 73.6 s(-1) for ATP and 40.5 s(
      1) for ADP. Control ADP-induced dimer (rK430) unbinding was 18.6 s(-1). Added 20
      mM Pi slowed both monomer and dimer unbinding. With the roadblock in place, lead
      head attachment of dimers is prevented and ATP-induced trail head unbinding was
      then 42 s(-1). This is less than two-fold slower than the stepping rate of
      unimpeded rK430 dimers (50-70 s(-1)), indicating that during walking, lead head
      attachment induces at most only a slight (less than two-fold) acceleration of
      trail head detachment. As we discuss, this implies a coordination model having
      very fast (>2000 s(-1)) ATP-induced attachment of the lead head, followed by
      slower, strain-sensitive ADP release from the lead head.

PMID- 14685259
TI  - Structure of nucleotide-binding domain 1 of the cystic fibrosis transmembrane
      conductance regulator.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding
      cassette (ABC) transporter that functions as a chloride channel. Nucleotide
      binding domain 1 (NBD1), one of two ABC domains in CFTR, also contains sites for
      the predominant CF-causing mutation and, potentially, for regulatory
      phosphorylation. We have determined crystal structures for mouse NBD1 in
      unliganded, ADP- and ATP-bound states, with and without phosphorylation. This
      NBD1 differs from typical ABC domains in having added regulatory segments, a
      foreshortened subdomain interconnection, and an unusual nucleotide conformation.
      Moreover, isolated NBD1 has undetectable ATPase activity and its structure is
      essentially the same independent of ligand state. Phe508, which is commonly
      deleted in CF, is exposed at a putative NBD1-transmembrane interface. Our results
      are consistent with a CFTR mechanism, whereby channel gating occurs through ATP
      binding in an NBD1-NBD2 nucleotide sandwich that forms upon displacement of NBD1
      regulatory segments.

PMID- 14685260
TI  - Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins.
AB  - Inositol 1,4,5-trisphosphate receptors (InsP(3)Rs) were recently demonstrated to
      be activated independently of InsP(3) by a family of calmodulin (CaM)-like
      neuronal Ca(2+)-binding proteins (CaBPs). We investigated the interaction of both
      naturally occurring long and short CaBP1 isoforms with InsP(3)Rs, and their
      functional effects on InsP(3)R-evoked Ca(2+) signals. Using several experimental
      paradigms, including transient expression in COS cells, acute injection of
      recombinant protein into Xenopus oocytes and (45)Ca(2+) flux from permeabilised
      COS cells, we demonstrated that CaBPs decrease the sensitivity of InsP(3)-induced
      Ca(2+) release (IICR). In addition, we found a Ca(2+)-independent interaction
      between CaBP1 and the NH(2)-terminal 159 amino acids of the type 1 InsP(3)R. This
      interaction resulted in decreased InsP(3) binding to the receptor reminiscent of
      that observed for CaM. Unlike CaM, however, CaBPs do not inhibit ryanodine
      receptors, have a higher affinity for InsP(3)Rs and more potently inhibited IICR.
      We also show that phosphorylation of CaBP1 at a casein kinase 2 consensus site
      regulates its inhibition of IICR. Our data suggest that CaBPs are endogenous
      regulators of InsP(3)Rs tuning the sensitivity of cells to InsP(3).

PMID- 14685261
TI  - Nbp2 targets the Ptc1-type 2C Ser/Thr phosphatase to the HOG MAPK pathway.
AB  - The yeast high osmolarity glycerol (HOG) pathway signals via the Pbs2 MEK and the
      Hog1 MAPK, whose activity requires phosphorylation of Thr and Tyr in the
      activation loop. The Ptc1-type 2C Ser/Thr phosphatase (PP2C) inactivates Hog1 by
      dephosphorylating phospho-Thr, while the Ptp2 and Ptp3 protein tyrosine
      phosphatases dephosphorylate phospho-Tyr. In this work, we show that the SH3
      domain-containing protein Nbp2 negatively regulates Hog1 by recruiting Ptc1 to
      the Pbs2-Hog1 complex. Consistent with this role, NBP2 acted as a negative
      regulator similar to PTC1 in phenotypic assays. Biochemical analysis showed that
      Nbp2, like Ptc1, was required to inactivate Hog1 during adaptation. As predicted
      for an adapter, deletion of NBP2 disrupted Ptc1-Pbs2 complex formation.
      Furthermore, Nbp2 contained separate binding sites for Ptc1 and Pbs2: the novel N
      terminal domain bound Ptc1, while the SH3 domain bound Pbs2. In addition, the
      Pbs2 scaffold bound the Nbp2 SH3 via a Pro-rich motif distinct from that which
      binds the SH3 domain of the positive regulator Sho1. Thus, Nbp2 recruits Ptc1 to
      Pbs2, a scaffold for both negative and positive regulators.

PMID- 14685262
TI  - Roles of SWI/SNF and HATs throughout the dynamic transcription of a yeast glucose
      repressible gene.
AB  - Eucaryotic gene expression requires chromatin-remodeling activities. We show by
      time-course studies that transcriptional induction of the yeast glucose-regulated
      SUC2 gene is rapid and shows a striking biphasic pattern, the first phase of
      which is partly mediated by the general stress transcription factors Msn2p/Msn4p.
      The SWI/SNF ATP-dependent chromatin-remodeling complex associates with the
      promoter in a similar biphasic manner and is essential for both phases of
      transcription. Two different histone acetyltransferases, Gcn5p and Esa1p, enhance
      the binding of SWI/SNF to the promoter during early transcription and are
      required for optimal SUC2 induction. Gcn5p is recruited to SUC2 simultaneously
      with SWI/SNF, whereas Esa1p associates constitutively with the promoter. This
      study reveals an unusual transcription pattern of a metabolic gene and suggests a
      novel strategy by which distinct chromatin remodelers cooperate for the dynamic
      activation of transcription.

PMID- 14685263
TI  - Identification of a family of animal sphingomyelin synthases.
AB  - Sphingomyelin (SM) is a major component of animal plasma membranes. Its
      production involves the transfer of phosphocholine from phosphatidylcholine onto
      ceramide, yielding diacylglycerol as a side product. This reaction is catalysed
      by SM synthase, an enzyme whose biological potential can be judged from the roles
      of diacylglycerol and ceramide as anti- and proapoptotic stimuli, respectively.
      SM synthesis occurs in the lumen of the Golgi as well as on the cell surface. As
      no gene for SM synthase has been cloned so far, it is unclear whether different
      enzymes are present at these locations. Using a functional cloning strategy in
      yeast, we identified a novel family of integral membrane proteins exhibiting all
      enzymatic features previously attributed to animal SM synthase. Strikingly,
      human, mouse and Caenorhabditis elegans genomes each contain at least two
      different SM synthase (SMS) genes. Whereas human SMS1 is localised to the Golgi,
      SMS2 resides primarily at the plasma membrane. Collectively, these findings open
      up important new avenues for studying sphingolipid function in animals.

PMID- 14685264
TI  - Regulated assembly of the Toll signaling complex drives Drosophila dorsoventral
      patterning.
AB  - In Drosophila, the Toll pathway establishes the embryonic dorsoventral axis and
      triggers innate immune responses to infection. The transmembrane receptor Toll
      acts through three death domain-containing proteins, the kinase Pelle and the
      adapters Tube and MyD88, in signaling to downstream NF-kappaB-like transcription
      factors. Here, we delineate the critical events in the earliest stages of Toll
      signaling. Mutational studies based on structural modeling reveal that the direct
      interaction of the bivalent Tube death domain with MyD88 is critical for
      signaling in vivo. The complex of MyD88 and Tube forms prior to signaling and is
      localized to the embryonic plasma membrane by MyD88. Upon Toll homodimerization,
      this complex is rapidly recruited to Toll. Binding of Pelle to the MyD88-Tube
      complex promotes Pelle activation, leading to degradation of the IkappaB-like
      inhibitor, Cactus. Together, these experiments convert a linear picture of gene
      function into a dynamic mechanistic and structural understanding of signaling
      complex assembly and function.

PMID- 14685265
TI  - Olfactory receptor antagonism between odorants.
AB  - The detection of thousands of volatile odorants is mediated by several hundreds
      of different G protein-coupled olfactory receptors (ORs). The main strategy in
      encoding odorant identities is a combinatorial receptor code scheme in that
      different odorants are recognized by different sets of ORs. Despite increasing
      information on agonist-OR combinations, little is known about the antagonism of
      ORs in the mammalian olfactory system. Here we show that odorants inhibit odorant
      responses of OR(s), evidence of antagonism between odorants at the receptor
      level. The antagonism was demonstrated in a heterologous OR-expression system and
      in single olfactory neurons that expressed a given OR, and was also visualized at
      the level of the olfactory epithelium. Dual functions of odorants as an agonist
      and an antagonist to ORs indicate a new aspect in the receptor code determination
      for odorant mixtures that often give rise to novel perceptual qualities that are
      not present in each component. The current study also provides insight into
      strategies to modulate perceived odorant quality.

PMID- 14685266
TI  - A novel role for XIAP in copper homeostasis through regulation of MURR1.
AB  - XIAP is a potent suppressor of apoptosis that directly inhibits specific members
      of the caspase family of cysteine proteases. Here we demonstrate a novel role for
      XIAP in the control of intracellular copper levels. XIAP was found to interact
      with MURR1, a factor recently implicated in copper homeostasis. XIAP binds to
      MURR1 in a manner that is distinct from that utilized by XIAP to bind caspases,
      and consistent with this, MURR1 did not affect the antiapoptotic properties of
      XIAP. However, cells and tissues derived from Xiap-deficient mice were found to
      contain reduced copper levels, while suppression of MURR1 resulted in increased
      intracellular copper in cultured cells. Consistent with these opposing effects,
      XIAP was observed to negatively regulate MURR1 protein levels by the formation of
      K48 polyubiquitin chains on MURR1 that promote its degradation. These findings
      represent the first described phenotypic alteration in Xiap-deficient mice and
      demonstrate that XIAP can function through MURR1 to regulate copper homeostasis.

PMID- 14685267
TI  - An episomal mammalian replicon: sequence-independent binding of the origin
      recognition complex.
AB  - An extrachromosomally replicating plasmid was used to investigate the specificity
      by which the origin recognition complex (ORC) interacts with DNA sequences in
      mammalian cells in vivo. We first showed that the plasmid pEPI-1 replicates
      semiconservatively in a once-per-cell-cycle manner and is stably transmitted over
      many cell generations in culture without selection. Chromatin
      immunoprecipitations and quantitative polymerase chain reaction analysis revealed
      that, in G1-phase cells, Orc1 and Orc2, as well as Mcm3, another component of the
      prereplication complex, are bound to multiple sites on the plasmid. These binding
      sites are functional because they show the S-phase-dependent dissociation of Orc1
      and Mcm3 known to be characteristic for prereplication complexes in mammalian
      cells. In addition, we identified replicative nascent strands and showed that
      they correspond to many plasmid DNA regions. This work has implications for
      current models of replication origins in mammalian systems. It indicates that
      specific DNA sequences are not required for the chromatin binding of ORC in vivo.
      The conclusion is that epigenetic mechanisms determine the sites where mammalian
      DNA replication is initiated.

PMID- 14685268
TI  - migS, a cis-acting site that affects bipolar positioning of oriC on the
      Escherichia coli chromosome.
AB  - During replication of the Escherichia coli chromosome, the replicated Ori domains
      migrate towards opposite cell poles, suggesting that a cis-acting site for
      bipolar migration is located in this region. To identify this cis-acting site, a
      series of mutants was constructed by splitting subchromosomes from the original
      chromosome. One mutant, containing a 720 kb subchromosome, was found to be
      defective in the bipolar positioning of oriC. The creation of deletion mutants
      allowed the identification of migS, a 25 bp sequence, as the cis-acting site for
      the bipolar positioning of oriC. When migS was located at the replication
      terminus, the chromosomal segment showed bipolar positioning. migS was able to
      rescue bipolar migration of plasmid DNA containing a mutation in the SopABC
      partitioning system. Interestingly, multiple copies of the migS sequence on a
      plasmid in trans inhibited the bipolar positioning of oriC. Taken together, these
      findings indicate that migS plays a crucial role in the bipolar positioning of
      oriC. In addition, real-time analysis of the dynamic morphological changes of
      nucleoids in wild-type and migS mutants suggests that bipolar positioning of the
      replicated oriC contributes to nucleoid organization.

PMID- 14685270
TI  - Drosophila Cup is an eIF4E-binding protein that functions in Smaug-mediated
      translational repression.
AB  - Translational regulation plays an essential role in development and often
      involves factors that interact with sequences in the 3' untranslated region (UTR)
      of specific mRNAs. For example, Nanos protein at the posterior of the Drosophila
      embryo directs posterior development, and this localization requires selective
      translation of posteriorly localized nanos mRNA. Spatial regulation of nanos
      translation requires Smaug protein bound to the nanos 3' UTR, which represses the
      translation of unlocalized nanos transcripts. While the function of 3' UTR-bound
      translational regulators is, in general, poorly understood, they presumably
      interact with the basic translation machinery. Here we demonstrate that Smaug
      interacts with the Cup protein and that Cup is an eIF4E-binding protein that
      blocks the binding of eIF4G to eIF4E. Cup mediates an indirect interaction
      between Smaug and eIF4E, and Smaug function in vivo requires Cup. Thus, Smaug
      represses translation via a Cup-dependent block in eIF4G recruitment.

PMID- 14685269
TI  - The multicoloured world of promoter recognition complexes.
AB  - The expression pattern of regulated genes changes dynamically depending on the
      developmental stage and the differentiation state of the cell. Transcription
      factors regulate cellular events at the gene expression level by communicating
      signals to the general transcription machinery that forms a preinitiation complex
      (PIC) at class II core promoters. Recent data strongly suggest that PICs are
      composed of different sets of factors at distinct promoters, reflecting the
      spatiotemporal profile of gene expression in multicellular organisms. Thus, today
      it is important to ask the question: how universal are the promoter recognition
      factors? This review will focus on findings that support the new idea that core
      promoter recognition by distinct factors is an additional level of
      transcriptional regulation and that this step is developmentally regulated.

PMID- 14685271
TI  - Modulation of KSR activity in Caenorhabditis elegans by Zn ions, PAR-1 kinase and
      PP2A phosphatase.
AB  - Vulval differentiation in Caenorhabditis elegans is controlled by a conserved
      signal transduction pathway mediated by Ras and a kinase cascade that includes
      Raf, Mek and MAPK. Activation of this cascade is positively regulated by a number
      of proteins such as KSR (kinase suppressor of Ras), SUR-8/SOC-2, SUR-6/PP2A-B and
      CDF-1. We describe the functional characterization of sur-7 and several genes
      that regulate signaling downstream of ras. We identified sur-7 by isolating a
      mutation that suppresses an activated ras allele, and showed that SUR-7 is a
      divergent member of the cation diffusion facilitator family of heavy metal ion
      transporters that is probably localized to the endoplosmic recticulum membrane
      and regulates cellular Zn(2+) concentrations. Genetic double mutant analyses
      suggest that the SUR-7-mediated effect is not a general toxic response. Instead,
      Zn(2+) ions target a specific step of the pathway, probably regulation of the
      scaffolding protein KSR. Biochemical analysis in mammalian cells indicates that
      high Zn(2+) concentration causes a dramatic increase of KSR phosphorylation.
      Genetic analysis also indicates that PP2A phosphatase and PAR-1 kinase act
      downstream of Raf to positively and negatively regulate KSR activity,
      respectively.

PMID- 14685272
TI  - Eucaryotic genome evolution through the spontaneous duplication of large
      chromosomal segments.
AB  - There is growing evidence that duplications have played a major role in
      eucaryotic genome evolution. Sequencing data revealed the presence of large
      duplicated regions in the genomes of many eucaryotic organisms, and comparative
      studies have suggested that duplication of large DNA segments has been a
      continuing process during evolution. However, little experimental data have been
      produced regarding this issue. Using a gene dosage assay for growth recovery in
      Saccharomyces cerevisiae, we demonstrate that a majority of the revertant strains
      (58%) resulted from the spontaneous duplication of large DNA segments, either
      intra- or interchromosomally, ranging from 41 to 655 kb in size. These events
      result in the concomitant duplication of dozens of genes and in some cases in the
      formation of chimeric open reading frames at the junction of the duplicated
      blocks. The types of sequences at the breakpoints as well as their superposition
      with the replication map suggest that spontaneous large segmental duplications
      result from replication accidents. Aneuploidization events or suppressor
      mutations that do not involve large-scale rearrangements accounted for the rest
      of the reversion events (in 26 and 16% of the strains, respectively).

PMID- 14685273
TI  - Identification of PKCzetaII: an endogenous inhibitor of cell polarity.
AB  - A new member of the atypical protein kinase C (aPKC) family, designated
      PKCzetaII, is identified in this study. The gene contains no introns and is 98%
      homologous with the cDNA encoding PKCzeta. The PKCzetaII coding region is frame
      shifted with respect to the PKCzeta open reading frame, resulting in expression
      of an aPKC regulatory domain without associated kinase activity. PKCzetaII mRNA
      is detected in various mouse tissues and an immunoreactive 45 kDa protein is
      present in epithelial cell cultures. PKCzetaII is shown to interact with the Par6
      protein and functions in the development of cell polarity. HC11 epithelial cells
      express PKCzetaII and are maintained in a nondifferentiated state characterised
      by the absence of tight junctions and cell overgrowth. HC11 cells harbouring a
      PKCzetaII-specific RNAi, recruit ZO-1 and other tight junction markers to cell
      cell boundaries and adopt a monolayer phenotype in the presence of growth
      factors. The data demonstrate a regulatory role for PKCzetaII in the maintenance
      of cell transformation and the development of cell polarity.

PMID- 14685274
TI  - Recruitment of Cdc28 by Whi3 restricts nuclear accumulation of the G1 cyclin-Cdk
      complex to late G1.
AB  - The G1 cyclin Cln3 is a key activator of cell-cycle entry in budding yeast. Here
      we show that Whi3, a negative G1 regulator of Cln3, interacts in vivo with the
      cyclin-dependent kinase Cdc28 and regulates its localization in the cell.
      Efficient interaction with Cdc28 depends on an N-terminal domain of Whi3 that is
      also required for cytoplasmic localization of Cdc28, and for proper regulation of
      G1 length and filamentous growth. On the other hand, nuclear accumulation of
      Cdc28 requires the nuclear localization signal of Cln3, which is also found in
      Whi3 complexes. Both Cln3 and Cdc28 are mainly cytoplasmic during early G1, and
      become nuclear in late G1. However, Whi3-deficient cells show a distinct nuclear
      accumulation of Cln3 and Cdc28 already in early G1. We propose that Whi3
      constitutes a cytoplasmic retention device for Cln3-Cdc28 complexes, thus
      defining a key G1 event in yeast cells.

PMID- 14685275
TI  - Structural bases for CRMP function in plexin-dependent semaphorin3A signaling.
AB  - Collapsin response mediator proteins (CRMPs) are cytosolic phosphoproteins
      involved in neuronal differentiation and axonal guidance. CRMP2 was previously
      shown to mediate the repulsive effect of Sema3A on axons and to participate in
      axonal specification. The X-ray crystal structure of murine CRMP1 was determined
      at 2.1 A resolution and demonstrates that CRMP1 is a bilobed 'lung-shaped'
      protein forming a tetrameric assembly. Structure-based mutagenesis of surface
      exposed residues was employed to map functional domains. As a rapid assay for
      CRMP, we exploited a reconstituted Sema3A signaling system in COS-7 cells
      expressing the receptor components Neuropilin1 and PlexinA1 (NP1/PlexA1). In
      these cells, CRMP and PlexA1 form a physical complex that is reduced in amount by
      NP1 but enhanced by Sema3A/NP1. Furthermore, CRMP accelerates Sema3A-induced cell
      contraction. Alanine substitutions in one domain of CRMP1 produce a
      constitutively active protein that causes Sema3A-independent COS-7 contraction.
      This mutant CRMP mimics the DRG neurite outgrowth-inhibiting effects of Sema3A
      and reduces Sema3A-induced axonal repulsion. These data provide a structural view
      of CRMP function in Plex-dependent Sema3A signaling.

PMID- 14685277
TI  - Unravelling natural killer cell function: triggering and inhibitory human NK
      receptors.
AB  - Natural killer (NK) cells represent a highly specialized lymphoid population
      characterized by a potent cytolytic activity against tumor or virally infected
      cells. Their function is finely regulated by a series of inhibitory or activating
      receptors. The inhibitory receptors, specific for major histocompatibility
      complex (MHC) class I molecules, allow NK cells to discriminate between normal
      cells and cells that have lost the expression of MHC class I (e.g., tumor cells).
      The major receptors responsible for NK cell triggering are NKp46, NKp30, NKp44
      and NKG2D. The NK-mediated lysis of tumor cells involves several such receptors,
      while killing of dendritic cells involves only NKp30. The target-cell ligands
      recognized by some receptors have been identified, but those to which major
      receptors bind are not yet known. Nevertheless, functional data suggest that they
      are primarily expressed on cells upon activation, proliferation or tumor
      transformation. Thus, the ability of NK cells to lyse target cells requires both
      the lack of surface MHC class I molecules and the expression of appropriate
      ligands that trigger NK receptors.

PMID- 14685276
TI  - Blocking HIV-1 infection via CCR5 and CXCR4 receptors by acting in trans on the
      CCR2 chemokine receptor.
AB  - The identification of chemokine receptors as HIV-1 coreceptors has focused
      research on developing strategies to prevent HIV-1 infection. We generated CCR2
      01, a CCR2 receptor-specific monoclonal antibody that neither competes with the
      chemokine CCL2 for binding nor triggers signaling, but nonetheless blocks
      replication of monotropic (R5) and T-tropic (X4) HIV-1 strains. This effect is
      explained by the ability of CCR2-01 to induce oligomerization of CCR2 with the
      CCR5 or CXCR4 viral coreceptors. HIV-1 infection through CCR5 and CXCR4 receptors
      can thus be prevented in the absence of steric hindrance or receptor
      downregulation by acting in trans on a receptor that is rarely used by the virus
      to infect cells.

PMID- 14685278
TI  - E2A proteins enforce a proliferation checkpoint in developing thymocytes.
AB  - E2A proteins regulate multiple stages of thymocyte development and suppress T
      cell lymphoma. The activity of E2A proteins throughout thymocyte development is
      modulated by signals emanating from the pre-TCR and TCR. Here we demonstrate that
      E2A is required for the complete arrest in both differentiation and proliferation
      observed in thymocytes with defects in proteins that mediate pre-TCR signaling,
      including LAT, Lck and Fyn. We show that E2A proteins are required to prevent the
      accumulation of TCRbeta negative cells beyond the pre-TCR checkpoint. E2A
      deficient thymocytes also exhibit abnormal cell-cycle progression prior to pre
      TCR expression. Furthermore, we demonstrate that E47 can act in concert with Bcl
      2 to induce cell-cycle arrest in vitro. These observations indicate that E2A
      proteins function during early thymocyte development to block cell-cycle
      progression prior to the expression of TCRbeta. In addition, these data provide
      further insight into how deficiencies in E2A lead to T lymphoma.

PMID- 14685279
TI  - Identification of a redox-regulated chaperone network.
AB  - We have identified and reconstituted a multicomponent redox-chaperone network
      that appears to be designed to protect proteins against stress-induced unfolding
      and to refold proteins when conditions return to normal. The central player is
      Hsp33, a redox-regulated molecular chaperone. Hsp33, which is activated by
      disulfide bond formation and subsequent dimerization, works as an efficient
      chaperone holdase that binds to unfolding protein intermediates and maintains
      them in a folding competent conformation. Reduction of Hsp33 is catalyzed by the
      glutaredoxin and thioredoxin systems in vivo, and leads to the formation of
      highly active, reduced Hsp33 dimers. Reduction of Hsp33 is necessary but not
      sufficient for substrate protein release. Substrate dissociation from Hsp33 is
      linked to the presence of the DnaK/DnaJ/GrpE foldase system, which alone, or in
      concert with the GroEL/GroES system, then supports the refolding of the substrate
      proteins. Upon substrate release, reduced Hsp33 dimers dissociate into inactive
      monomers. This regulated substrate transfer ultimately links substrate release
      and Hsp33 inactivation to the presence of available DnaK/DnaJ/GrpE, and,
      therefore, to the return of cells to non-stress conditions.

PMID- 14685280
TI  - The SNARE Ykt6 mediates protein palmitoylation during an early stage of homotypic
      vacuole fusion.
AB  - The NSF homolog Sec18 initiates fusion of yeast vacuoles by disassembling cis
      SNARE complexes during priming. Sec18 is also required for palmitoylation of the
      fusion factor Vac8, although the acylation machinery has not been identified.
      Here we show that the SNARE Ykt6 mediates Vac8 palmitoylation and acts during a
      novel subreaction of vacuole fusion. This subreaction is controlled by a Sec17
      independent function of Sec18. Our data indicate that Ykt6 presents Pal-CoA via
      its N-terminal longin domain to Vac8, while transfer to Vac8's SH4 domain occurs
      spontaneously and not enzymatically. The conservation of Ykt6 and its
      localization to several organelles suggest that its acyltransferase activity may
      also be required in other intracellular fusion events.

PMID- 14685281
TI  - Collagen XVIII/endostatin is essential for vision and retinal pigment epithelial
      function.
AB  - Age-related macular degeneration (ARMD) with abnormal deposit formation under the
      retinal pigment epithelium (RPE) is the major cause of blindness in the Western
      world. basal laminar deposits are found in early ARMD and are composed of excess
      basement membrane material produced by the RPE. Here, we demonstrate that mice
      lacking the basement membrane component collagen XVIII/endostatin have massive
      accumulation of sub-RPE deposits with striking similarities to basal laminar
      deposits, abnormal RPE, and age-dependent loss of vision. The progressive
      attenuation of visual function results from decreased retinal rhodopsin content
      as a consequence of abnormal vitamin A metabolism in the RPE. In addition, aged
      mutant mice show photoreceptor abnormalities and increased expression of glial
      fibrillary acidic protein in the neural retina. Our data demonstrate that
      collagen XVIII/endostatin is essential for RPE function, and suggest an important
      role of this collagen in Bruch's membrane. Consistent with such a role, the
      ultrastructural organization of collagen XVIII/endostatin in basement membranes,
      including Bruch's membrane, shows that it is part of basement membrane molecular
      networks.

PMID- 14685282
TI  - Silencing of transgene transcription precedes methylation of promoter DNA and
      histone H3 lysine 9.
AB  - Transgenes stably integrated into cells or animals in many cases are silenced
      rapidly, probably under the influence of surrounding endogenous condensed
      chromatin. This gene silencing correlates with repressed chromatin structure
      marked by histone hypoacetylation, loss of methylation at H3 lysine 4, increase
      of histone H3 lysine 9 methylation as well as CpG DNA methylation at the
      promoter. However, the order and the timing of these modifications and their
      impact on transcription inactivation are less well understood. To determine the
      temporal order of these events, we examined a model system consisting of a
      transgenic cassette stably integrated in chicken erythroid cells. We found that
      histone H3 and H4 hypoacetylation and loss of methylation at H3 lysine 4 all
      occurred during the same window of time as transgene inactivation in both
      multicopy and low-copy-number lines. These results indicate that these histone
      modifications were the primary events in gene silencing. We show that the
      kinetics of silencing exclude histone H3 K9 and promoter DNA methylation as the
      primary causative events in our transgene system.

PMID- 14685284
TI  - External whole-body image of EGFP gene expression.
AB  - Whole-body optical imaging is an external and noninvasive procedure that enables
      the continuous visual monitoring of malignant growth and spread within intact
      animals. The human colon adenocarcinoma cell-line HCT-15 was transfected with a
      pIRES 2-EGFP vector, and stable enhanced green fluorescence protein (EGFP)
      expression was established (Fig.1). Approximately 10(6) HCT-15 EGFP stable
      transfectant cells were subcutaneously injected into the left flank of six-week
      old male Balb/c-nu/nu mice. On post-injection day 78, the size of the
      subcutaneous tumor was 13.1 mm x 15.4 mm in diameter, as observed using an ORCA-C
      7780-20 three-chip cooled color charge-coupled-device camera (Hamamatsu Photonics
      Systems, Hamamatsu City, Japan). An external fluorescent image of the tumor was
      acquired through the skin (Fig.2B). The tumor could be seen more clearly once the
      skin was removed (Fig.2D). Furthermore, in the peritoneal metastasis (Fig.3B) and
      liver metastasis models (Fig.3D), metastasis could also be seen through the skin.
      This new technology is a useful method for investigating tumor growth in vivo. In
      the future, this method could be applied to the detection of peritoneal, liver
      and lung metastasis in living animals.

PMID- 14685283
TI  - Isomerization of the intersubunit disulphide-bond in Env controls retrovirus
      fusion.
AB  - The membrane fusion activity of murine leukaemia virus Env is carried by the
      transmembrane (TM) and controlled by the peripheral (SU) subunit. We show here
      that all Env subunits of the virus form disulphide-linked SU-TM complexes that
      can be disrupted by treatment with NP-40, heat or urea, or by Ca(2+) depletion.
      Thiol mapping indicated that these conditions induced isomerization of the
      disulphide-bond by activating a thiol group in a Cys-X-X-Cys (CXXC) motif in SU.
      This resulted in dissociation of SU from the virus. The active thiol was hidden
      in uninduced virus but became accessible for alkylation by either Ca(2+)
      depletion or receptor binding. The alkylation inhibited isomerization, virus
      fusion and infection. DTT treatment of alkylated Env resulted in cleavage of the
      SU-TM disulphide-bond and rescue of virus fusion. Further studies showed that
      virus fusion was specifically inhibited by high and enhanced by low
      concentrations of Ca(2+). These results suggest that Env is stabilized by Ca(2+)
      and that receptor binding triggers a cascade of reactions involving Ca(2+)
      removal, CXXC-thiol exposure, SU-TM disulphide-bond isomerization and SU
      dissociation, which lead to fusion activation.

PMID- 14685285
TI  - Treatment and prevention of diabetic ketoacidosis in children and adolescents.

PMID- 14685286
TI  - [A report of questionnaire survey asking teaching staff concerning evaluation of
      faculty teaching from the students in Nippon Medical School].
AB  - A questionnaire survey was conducted to ask teaching staffs about the present
      activities and opinions of evaluation of faculty teaching from the students
      (EFS). One hundred and eighty-eight among 336 members (56.1%) responded. Among
      them sixty-four (34%) replied that they had tried at least once EFS of their
      lectures and/or practices. Approximately 70% had a opinion that EFS would benefit
      them for improving their lectures and practices, and/or for improving course
      planning. Fifty-four per cent of members supported EFS to be introduced, 34%
      depended upon how to evaluate, and remaining 5% did not support it. These results
      indicate that the staff members are highly concerned with EFS which should be
      provided for introduction after a full discussion how to evaluate.

PMID- 14685287
TI  - Effects of intravenous infusion rate of oxytocin on thoracic epidural pressure in
      parturients undregoing elective cesarean section.
AB  - The effects of intravenous oxytocin on thoracic epidural pressure during cesarean
      section were studied in 90 parturients (American Society of Anesthesiologists
      physical atatus class I or II) after obtaining informed consent. The subjects
      were randomized to either a control (control group; n=30), bolus (bolus group;
      n=30) or drip treatment group (drip group; n=30). The subjects were anesthetized
      with 11 approximately 12 mg of intrathecal isobaric bupivacaine (0.5%). An
      epidural catheter placed at Th 11/12 was connected to a pressure transducer to
      continuously monitor thoracic epidural pressure. Ten units of oxytocin were
      administered over 30 seconds in the bolus group and over 5 minutes in the drip
      group after fetus delivery. We analyzed epidural pressure, mean blood pressure,
      and heart rate, until 5 minutes after fetus delivery. Epidural pressures in both
      bolus and drip groups increased after fetus delivery compared with control group
      (P<0.0001). Epidural pressure immediately after placental delivery in the bolus
      group was higher than in the control group (p<0.0001) and epidural pressure at 5
      minutes after fetus delivery in the drip group was higher than in the control
      group (p=0.0452). There were no significant differences in changes in blood
      pressure and heart rate among the three groups. We concluded that the increase in
      epidural pressure with intravenous administration of oxytocin 10 units over 5
      minutes was lower than with intravenous administration of oxytocin 10 units over
      30 seconds after fetus delivery.

PMID- 14685288
TI  - Changes in plasma endothelin-1 after elective cesarean section in women with
      preeclampsia and the relationship to thrombocytopenia.
AB  - OBJECTIVE: The aim of this study was to clarify the time course of plasma
      endothelin-1 levels and platelet counts after elective cesarean section in women
      with preeclampsia, and to investigate the relationship between them
      postoperatively. METHODS: We studied 20 patients with preeclampsia and 25 healthy
      pregnant women without preeclampsia who underwent cesarean section and 20 women
      without preeclampsia who had vaginal deliveries. The plasma endothelin-1 and
      platelet counts were measured serially after cesarean section. RESULTS: 1) In
      patients with preeclampsia, plasma endothelin-1 levels peaked on postoperative
      day 0 (p<0.05), and remained high, then fell to the preoperative level from day
      5. The concentration was lower in healthy pregnant women undergoing cesarean
      section than in patients with preeclampsia before surgery, but showed a gradual
      significant increase from postoperative day 0 to postoperative day 3 (p<0.05)
      before falling. The women who underwent vaginal delivery showed a peak level of
      endothelin-1 on the day of delivery but this fell rapidly between day 3. 2) Women
      with preeclampsia showed a negative correlation between plasma endothelin-1
      levels and platelet counts after cesarean section (r=0.46, p<0.01), while women
      without preeclampsia undergoing cesarean and vaginal deliveries did not.
      CONCLUSION: Endothelin-1 production is stimulated after cesarean section, which
      is paralleled with postpartal thrombocytopenia only in patients with
      preeclampsia.

PMID- 14685289
TI  - Increased chymase in livers with autoimmune disease: colocalization with
      fibrosis.
AB  - Chymase, one of the proteases contained in human mast cells, promotes myocardial
      and renal interstitial fibrosis by converting angiotensin I to II (AII). We
      previously established a method for measuring chymase in liver tissue and
      examined the relationship between chymase and fibrosis in chronic hepatitis. In
      the present study, chymase was determined in liver specimens affected by
      autoimmune hepatitis (AIH, n=10) or primary biliary cirrhosis (PBC, n=12). To
      investigate spatial relationships between hepatic fibrosis and human chymase,
      mast cell distribution in the specimens was determined immunohistochemically
      using anti-chymase antibody. The mean amounts of chymase in livers with AIH and
      PBC were 11.56+/-10.64 and 11.67+/-9.96 ng/mg respectively. Hepatic chymase in
      AIH and PBC was significantly more abundant than in acute hepatitis (AH, 2.72+/
      2.23 ng/mg, n=10; p<0.05). When sections from patients with AIH and PBC were
      immunostained for chymase, immunoreactive mast cells were detected in portal
      areas and sinusoidal walls, coinciding with zones of fibrosis. Thus chymase
      appears to be involved in hepatic fibrosis in AIH and PBC.

PMID- 14685290
TI  - [Comparative study on the sclerotic changes of cardiac valve and blood vessel].
AB  - BACKGROUND: Recently, there is an increase in number of surgical treatments for
      the aortic stenosis caused by valvular sclerosis with aging. Whether valvular
      sclerosis are related to aortic atherosclerosis, the prevention therapy of
      arteriosclerosis may benefit the clinical treatment of the valvular dysfunction
      due to aging. MATERIALS AND METHODS: Gross, histological and immunohistochemical
      studies were made on 159 autopsy cases (97 men, 62 women, mean age 65.1 years
      old). The degree of sclerotic change in aortic valve (AV), mitral valve (MV),
      aorta (Ao) and coronary artery (CA) was classified by gross examination to none,
      mild, moderate, and severe, scored as 0 to 3, respectively. The data were
      statistically analyzed by the correlation test. To observe the expression of bone
      related proteins in valve calcification, indirect immunostaining procedures were
      applied with antibodies to osteocalcin, osteopontin and osteonectin. RESULTS:
      Grossly, there was a significant correlation in sclerotic change between Ao and
      AV, Ao and MV, AV and MV, CA and AV, and CA and MV, respectively (p<0.01). Also,
      the degree of sclerotic change in each tissue was correlated with patients'age.
      However, the grade of sclerotic change of each tissue was variant in each case.
      On gross observation, all valvular sclerosis showed yellowish thickening and/or
      calcification. Microscopically, hyalinous change of the fibrosa was observed in
      the yellowish lesion of the valves. Accumulations of foamy macrophages were found
      focally at the surface area of the fibrosa, but no atheromatous change was
      observed in the valves. Calcified deposits, if present, were found in the fibrous
      valvular ring or fibrosa with hyalinous degeneration. In MV, calcification was
      usually localized in the fibrous ring. However, in AV, valvular calcification
      extended diffusely in the fibrosa and caused stenosis in some cases. These
      lesions were similar to calcified area in the intima with fibrous thickening of
      Ao and/or CA, but were different from atheromatous lesion of these tissues.
      Immunohistochemically, calcified areas of valves showed stronger reaction for
      osteocalcin than that of vessels. CONCLUSION: Among sclerotic change of cardiac
      valves and arteriosclerosis, statistical correlations were found, but
      pathological features were different. Main causes of these differences are
      thought to be 1) not only the shear stress, but also intramural pressure and
      mechanical stress with opening and closing may interfere the sclerotic change of
      cardiac valves, and 2) mechanism of valvular sclerosis may be different from
      arteriosclerosis because medial smooth muscle cells are absent in the valves.

PMID- 14685291
TI  - [Long-term remnants of coagulation necrosis of cardiomyocytes following
      myocardial infarction].
AB  - Remnants of cardiomyocytes showing coagulation necrosis in the scars caused by
      myocardial infarction were histopathologically studied. Among 305 autopsy cases
      of acute and/or healed myocardial infarction, 8 cases (7 men, 1 woman, ages 62 -
      87 years, mean age 72.1) had masses of cardiomyocytes with coagulation necrosis
      at the center of the infarction scars more than 3 weeks (21 to 79 days) after the
      attack of myocardial infarction. All these cases had transmural infarction and
      more than 80% of the wall thickness of the left ventricle was involved in the
      infarction. No polymorphonuclear leukocytic infiltration or granulation tissue
      was found in the necrotic area, but macrophages were observed in the peripheral
      area adjacent to the scar tissue. Immunohistochemical staining for myoglobin
      showed no reaction in remnant necrotic cells or pericellular interstitium, which
      was similar to findings in the necrotic area more than 4 days after the
      infarction. These findings are important in the pathological diagnosis to
      distinguish remnant necrosis from acute necrosis, because 4 out of 8 present
      cases (50%) were misdiagnosed as acute myocardial infarction that superimposed on
      the previous old infarction.

PMID- 14685292
TI  - Infected solitary hepatic cyst.
AB  - An unusual case involving an infected hepatic cyst in which the correct diagnosis
      was made without operation is reported. A 93-year-old woman presented with acute
      onset of right upper quadrant abdominal pain, mild left lower quadrant abdominal
      pain, diarrhea, and fever. On admission, computed tomography revealed a 15 cm
      solitary hepatic cyst in the anterior-superior segment of the liver with a
      thickened wall that enhanced with contrast media. Ultrasonography demonstrated a
      15 cm anechoic lesion with a hypoechoic area in the dependent portion of the cyst
      and a thickened wall. The serum concentration of C-reactive protein was 24.3
      mg/dL, and the white blood cell count was 13,800/microL. A diagnosis of infected
      hepatic cyst was suspected, and percutaneous transhepatic drainage of the cyst
      was performed. Milky yellow fluid was obtained and the patient's right upper
      quadrant abdominal pain resolved after drainage. Klebsiella pneumoniae was
      cultured from the drainage fluid. The patient was discharged 20 days after
      drainage. Infection has not recurred and the hepatic cyst has not enlarged after
      18 months.

PMID- 14685293
TI  - Traumatic perilymph fistula in infants: a case report.
AB  - Traumatic perilymph fistula is reported to be rare in infants because of the
      small size of the infant external meatus. We treated an infant with a traumatic
      perilymph fistula in the right ear. A metallic wire had penetrated the tympanic
      membrane. Horizontal-rotatory nystagmus was also observed. Computed tomographic
      images revealed dislocation of the ossicles. The perilymph fistula was closed
      under general anesthesia. The incus-stapes joint was separated and the footplate
      of the stapes was dislocated. Leakage of the perilymph fluid was apparent from
      the oval window and this fistula was closed with connective tissue. The
      perforation of the tympanic membrane was closed with temporal fascia. After
      surgery, the spontaneous nystagmus disappeared. The patient is under observation
      as an outpatient and is growing normally.

PMID- 14685294
TI  - [Postoperative management and complications in living-related liver
      transplantation].
AB  - Living-related liver transplantation is widely accepted as a treatment for
      patients with end-stage liver disease, with survival rates of up to 80%. Liver
      transplant recipients are at risk for the same postoperative complications as any
      patient undergoing a major intraabdominal operation, in addition to several
      complications specific to this procedure. Maintenance immunosuppression relies
      principally on administration of tacrolimus and methylprednisolone. Nevertheless,
      approximately 36% of liver transplant recipients suffer acute rejection in the
      early posttransplant period and require bolus steroid therapy as a rescue agent.
      Vascular complications, including hepatic arterial thrombosis and portal vein
      thrombosis, are additional major problems. When they occur in the immediate
      postoperative period, they can produce fulminant hepatic necrosis requiring
      retransplantation, so intensive anticoagulation therapy is needed as prophylaxis
      against these vascular complications. If thrombosis of the hepatic artery or
      portal vein is diagnosed early in the postoperative course, emergency
      thrombectomy with reanastomosis should be attempted. Outflow obstruction by
      hepatic vein stenosis sometimes causes liver dysfunction, pleural effusion, and
      hepatosplenomegaly. Percutaneous transhepatic or transjugular approached hepatic
      vein dilatation is very useful in case of hepatic vein stenosis. Recipients are
      generally immunocompromised secondary to immunosuppressive therapy and their poor
      clinical condition and are at high risk for postoperative infection. Infection is
      a major cause of morbidity and the most common cause of death in liver transplant
      recipients. Antibiotic, antifungal, and antiviral agents are used empirically,
      and serologic examinations and bacterial investigations of blood, sputum, stool,
      urine, and discharge from drains should be performed as well as antibiotic
      sensitivity tests when necessary. Other complications related to the operation
      are intraabdominal bleeding, bile leakage, biliary anastomotic stenosis, and
      intestinal perforation. The postoperative course of liver transplant recipients
      with these complications depends on making an accurate diagnosis promptly and
      initiating appropriate management. Postoperative complications of living-related
      liver transplantation are protean, so it is very important to communicate with
      professionals in each specialized field to ensure optimal treatment.

PMID- 14685295
TI  - Direct phosphorylation of histamine H1 receptor by various protein kinases in
      vitro.
AB  - Phosphorylation of G protein-coupled receptors (GPCRs) by various kinases is
      suggested to be an important step in initiating receptor desensitization. Some
      reports have indirectly demonstrated the involvement of protein kinase C (PKC)
      mediated receptor phosphorylation in the desensitization of the histamine H1
      receptor (H1R). In this study, human c-myc-epitope-tagged H1R (hm mcH1R) was
      expressed in Sf9 cells, and an in vitro approach was taken to obtain direct
      evidence that H1R could be phosphorylated by various kinases. When hm mcH1R,
      which had been immunoprecipitated with anti-c-myc antibody from Sf9 cell
      membranes, was incubated with PKC, cAMP-dependent protein kinase (PKA),
      calcium/calmodulin-dependent protein kinase II (CaMKII) or cGMP-dependent protein
      kinase (PKG), the immunoprecipitated receptor was phosphorylated by these
      kinases. Membrane-bound hm mcH1R, whose conformation is closer to its
      physiological state than that of the immunoprecipitated receptor, was also
      phosphorylated by PKC, PKA, CaMKII and PKG. Phosphorylation of immunoprecipitated
      and membrane-bound hm mcH1R was inhibited by kinase inhibitors. These data are
      the first demonstration of the phosphorylation of H1R by four protein kinases,
      i.e., PKC, PKA, CaMKII and PKG, and provide fundamental information to help us
      further understand the relationship between H1R phosphorylation and
      desensitization of this receptor.

PMID- 14685296
TI  - Effect of hydrogen peroxide on amino acid concentrations in bovine retina and
      vitreous humor, ex vivo.
AB  - In a previous study, we showed evidence that oxidative stress induced by hydrogen
      peroxide (H2O2) can inhibit the release of [3H]-D-aspartate from the bovine
      isolated retina, in vitro. The aim of the present study was to investigate the
      effect of H2O2 on glutamate and glycine levels in the bovine retina and vitreous
      humor, ex vivo. Furthermore, we examined whether inhibition of catalase activity
      with 3-amino-triazole had any effect on the concentrations of these amino acids
      in the posterior segment of the bovine eye. Whole eye organ cultures were
      prepared by incubating tissues in oxygenated Krebs solution at 37 masculine C for
      30 min. After incubation, H2O2 (1-100 microM) or sterile distilled water was
      injected intravitreally into each eye. Thirty minutes after injection, the retina
      and vitreous humor were removed for analysis of glutamate and glycine by high
      performance liquid chromatography (HPLC) with fluorescence detection. Exogenously
      applied H2O2 (1-100 microM) caused a concentration-related decrease in both
      glutamate and glycine levels in the bovine retina. Furthermore, while H2O2 (1-10
      microM) caused a concentration-dependent decrease in glycine levels in the
      vitreous humor, it had no significant effect on glutamate levels. The catalase
      inhibitor, 3-amino-triazole (10 mM), caused a significant reduction in both
      glutamate and glycine levels in the bovine retina, ex vivo. Likewise, 3-AT caused
      an attenuation in both glutamate and glycine concentration in the vitreous humor.
      We conclude that oxidative stress induced by H2O2 can alter the release and/or
      availability of amino acids in the posterior segment of bovine eyes.

PMID- 14685297
TI  - 188Re-labeled anti-epidermal growth factor receptor humanized monoclonal antibody
      h-R3: labeling conditions, in vitro and in vivo stability.
AB  - The use of antibodies as targeting agents for the delivery of radioisotopes to
      tumors is an appealing concept that has received widespread attention since the
      advent of monoclonal antibody (mAb) technology. The present study describes the
      (188)Re-direct labeling of anti-epidermal growth factor receptor (EGF-R)
      humanized mAb h-R3; the analytical methods for quality control of
      radiopharmaceuticals such as instant thin layer chromatography-silica gel (ITLC
      SG); the immunoreactivity and biological recognition of the target antigen
      assessment of the radiolabeled molecule using flow cytometry analysis; in vitro
      stability studies using saline 0.9% solution, cysteine,
      diethylenetriaminepentaacetic acid (DTPA), human serum and human serum albumin
      (HSA) 1% challenge; and the assessment of in vivo stability through
      biodistribution studies in normal Balb/c mice. No fragmentation of the reduced
      molecules was found using 2-ME as a reducing agent. Labeling efficiency was
      greater than 98.5 +/- 0.6% of rhenium-188 (188Re) bound to IgG1 after 5 h, as
      determined by paper chromatography in saline 0.9% solution. Radiocolloids
      determined by albumin impregnated ITLC was 1.04 +/- 0.07% in all cases. The
      biological activity measured by flow cytometry analysis showed an
      immunoreactivity fraction and the biological recognition of the target antigen
      overexpressed on H-125 human lung adenocarcinoma cell line greater than 87%.
      Challenge studies with cysteine, DTPA, human serum and HSA 1% demonstrated no
      evidence of transcomplexation of 188Re to DTPA or HSA and showed that 30% and 85%
      of the 188Re-radiolabeled was transcomplexed to human serum and to 100 mM
      cysteine after 24 h for human serum and 1 h incubation for cysteine at 37
      masculine C, respectively. Biodistribution studies indicated no accumulation of
      the radiolabeled antibodies in normal organs.

PMID- 14685298
TI  - Measurement of beta-galactosidase tissue levels in a tumor cell xenograft model.
AB  - The nude mouse xenograft model is commonly used to examine the growth and
      development of human cancer cells in vivo. Tumor cells transfected with the Lac-Z
      reporter gene for beta-galactosidase (beta-gal) enzyme activity can be used to
      quantify tumor and metastatic development in this model. The present study was
      designed to develop methodology to accurately measure beta-gal in tumor and
      tissue samples from a nude mouse model. In this study, we developed tissue
      extraction procedures and compared the sensitivity and accuracy of o-nitrophenyl
      beta-D-galactopyranoside (ONPG) and chlorophenol red beta-D-galactopyranoside
      (CPRG); two beta-gal substrates. Our results demonstrated that the CPRG substrate
      is more sensitive and accurate in the measurement of beta-gal activity than the
      ONPG substrate. In addition, matrices and blood in tissue samples are less likely
      to interfere with the CPRG assay. We concluded that the CPRG substrate-based
      assay represents a reliable technique for the determination of beta-gal activity
      in transfected cancer cells present in tumor and tissue specimens from the nude
      mouse xenograft model.

PMID- 14685299
TI  - Determination of selective biochemical variables in pregnant and lactating mice
      after stobadine administration.
AB  - The aim of this study was to investigate the effects of the oral administration
      of stobadine (STB), a neuro- and cardioprotective drug with high antioxidant
      properties, on selective biochemical variables in pregnant and lactating mice.
      STB was administered orally at a dose of 50 mg/kg from day 15 of gestation to day
      21 of lactation. Creatinine and urea were determined in serum, while acidity,
      proteins, glucose, ketones, bilirubin, urobilinogen, blood and creatinine were
      determined in urine from females on days 0, 15 and 18 of gestation and on days 7,
      14, 21, and 28 postpartum (pp). In the biochemical variables investigated, no
      significant differences in STB-treated animals compared with controls were
      recorded on any of the days studied. Histopathological examination of kidney
      tissue did not reveal any adverse effect of STB administration.

PMID- 14685300
TI  - Prolonged treatment with isoproterenol causes a loss of myocardial Gsalpha mRNA
      expression.
AB  - We investigated the influence of chronic beta-adrenergic stimulation on Gsalpha
      protein gene expression and beta-adrenoceptor responsiveness in rat ventricular
      myocardium. The rats received twice-daily injections of 4 mg/kg isoproterenol
      (ISO) alone or with 8 mg/kg propranolol (PROP) for 4 days. In ventricular
      myocardium, Gsalpha mRNA expression decreased by 27% after ISO treatment. Dose
      dependent (10 nM to 100 micro M) positive inotropic responses by ISO in the left
      papillary muscles were lower after ISO treatment than in saline-treated
      myocardium with decreases in ED50 values. PROP itself had no effect, although it
      antagonized both ISO-induced effects. These results suggest that impaired Galpha
      mRNA expression may explain the loss of cardiac Gsalpha subunit levels after
      chronic beta-adrenergic stimulation, and that these changes can provide one
      mechanism for the progress of long-term desensitization.

PMID- 14685302
TI  - Bioinformatic insight into the unity and diversity of cytochromes P450.
AB  - For the past few decades, cytochromes P450 (CYPs) have been the subject of
      extensive research, owing to the ability of these enzymes to serve as drug
      targets as well as to their active participation in drug metabolism. Other
      varieties and functions of CYPs have been discovered and this superfamily
      currently comprises over 2000 different protein species. In the present study,
      the protein sequences of CYPs were submitted to computer analysis for elucidation
      of the structural basis of their pronounced functional diversity. The basic local
      alignment search tool (BLAST) was used to demonstrate that CYP protein sequences
      share a certain general similarity; at the same time, it was shown that the CYP
      superfamily may be split into a number of groups of intimately related proteins.
      These groups, the families, were revealed by means of cluster analysis, which
      demonstrated a strong hierarchy among the animal, bacterial and fungal P450s, and
      the lack of such a hierarchy for plant enzymes. Multiple alignment and consensus
      sequence analysis were the approaches taken to find out which structural
      peculiarities of P450s are responsible for the deviations from the random
      picture. Proteins within each family were aligned and collapsed to the
      corresponding consensus sequences, the alignment of which produced the consensus
      for the whole superfamily. The latter consensus yielded a number of unity motifs
      (most of which being related to the heme-fixing assembly), while the cross-family
      comparison of consensus sequences enabled the retrieval of some diversity motifs.
      Three consensus sequences (for the CYP51 and CYP2 families and for the
      superfamily) were compared, to line up the unity and diversity motifs with the
      appropriate X-ray data.

PMID- 14685301
TI  - Differential effects of the 5-HT1A agonist gepirone on food intake in rats may
      depend on their motivation to eat.
AB  - It has previously been suggested that the differential effects of 5
      hydroxytryptamine1A (5-HT1A) receptor agonists on food intake in non-deprived and
      food-deprived animals may be related to their motivation to feed. The present
      study was therefore conducted to investigate a possible relationship between the
      effects of the 5HT1A agonist gepirone on food intake in rats and their motivation
      to eat. In the first experiment, motivation to feed was varied by depriving the
      rats of food for different periods of time. In the second experiment, motivation
      to feed was varied by presenting them with highly palatable food. The results
      obtained from the first experiment showed that gepirone (1-4 mg/kg) increased
      food intake in non-deprived rats but decreased intake in 5-h and 22-h fasted
      animals. The extent of the hypophagia was related to the time the animals were
      fasted. The results from the second experiment showed that gepirone (0.5-5 mg/kg)
      reduced food intake in non-deprived rats presented with a highly palatable diet.
      The results obtained in this study suggest that the effects of gepirone on food
      intake may be related to the motivation of the animals to eat.

PMID- 14685303
TI  - Gateways to clinical trials.
AB  - Gateways to Clinical Trials is a guide to the most recent clinical trials in
      current literature and congresses. The data in the following tables has been
      retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity,
      the drug discovery and development portal, http://integrity.prous.com. This issue
      focuses on the following selection of drugs: Abarelix, ABX-EGF, ademetionine,
      agomelatine, AMGN-0007, 9-aminocamptothecin, AN-9, anecortave acetate,
      anidulafungin, AOD-9604, apolizumab, apomate, L-arginine hydrochloride,
      arzoxifene hydrochloride; Bevacizumab, BP-897, BufferGel; Capravirine,
      carboxyamidotriazole, carnosine, CC-4047, CEP-701, cerivastatin sodium,
      clofarabine, conivaptan hydrochloride, CP-461, CS-003; Daptomycin, darifenacin,
      decitabine, deferasirox, duloxetine hydrochloride; Eberconazole, Ecyd,
      efalizumab, eglumegad hydrate, EMD-72000, (-)-epigallocatechin gallate, exatecan
      mesilate, exenatide; Fampridine, fenretinide, ferumoxtran-10; Gadofosveset
      sodium, garenoxacin mesilate, genistein, glutamine, GPI-15715; Hexyl insulin M2,
      human insulin, HYB-165; Indisulam, irofulven; KRN-5500, L-796568, laurocapram,
      lidocaine/prilocaine, lonafarnib, lotrafiban; Melagatran, melatonin, 2
      methoxyestradiol, metreleptin, motexafin gadoliniu, motexafin lutetium;
      Natalizumab, nelarabine, NO-aspirin, NSC-683864; ONO-6126; Pemetrexed disodium,
      pexelizumab, pirfenidone, PncCRM9, polyglutamate paclitaxel, pramlintide acetate
      pregabalin, PRO-2000; Ragaglitazar, ramelteon, rasagiline mesilate, rDNA insulin,
      recombinant glucagon-like peptide-1 (7-36) amide, recombinant human parathyroid
      hormone (1-84), reolysin RG228, roflumilast, roxifiban acetate, RPI-4610,
      rubitecan; Safinamide mesilate, solifenacin succinate, SRL-172; T-138067,
      tafenoquine succinate, tecadenoson, TER-286, tesaglitazar, tetrathiomolybdate,
      tezosentan disodium, TheraCIM, tigecycline, tipifarnib, tolvaptan, trabectedin,
      tributyrin, trimegestone, troxacitabine; UCN-01, urokinase alfa; Vinflunine,
      viscum fraxini 2; Xcellerated T cells, ximelagatran.

PMID- 14685304
TI  - Use of opioid analgesics for the treatment of chronic noncancer pain--a consensus
      statement and guidelines from the Canadian Pain Society, 2002.

PMID- 14685305
TI  - New biophysical probes for structure-activity analyses of vacuolar-H+ -ATPase
      enzymes.
AB  - New EPR spin labelled and photoactivatable molecules have been designed to probe
      specifically the vacuolar-H(+)-ATPase.

PMID- 14685306
TI  - Synthesis of the cyclobutanone core of solanoeclepin A intramolecular allene
      butenolide photocycloaddition.
AB  - The compact tricyclic substructure of solanoeclepin A containing the
      cyclobutanone ring was prepared by using as the key step a highly regioselective
      intramolecular [2 + 2]-photocycloaddition reaction between one of the [small pi]
      bonds of an allene and the CC double bond of a butenolide.

PMID- 14685307
TI  - Isoprenoid biosynthesis via the MEP pathway. Synthesis of (3,4)-3,4-dihydroxy-5
      oxohexylphosphonic acid, an isosteric analogue of 1-deoxy-D-xylulose 5-phosphate,
      the substrate of the 1-deoxy-D-xylulose 5-phosphate reducto-isomerase.
AB  - (3,4)-3,4-Dihydroxy-5-oxohexylphosphonic acid, an isosteric analogue of 1-deoxy-D
      xylulose 5-phosphate (DXP), was obtained in enantiomerically pure form from (+)
      2,3--benzylidene--threitol by a seven-step sequence. This phosphonate did not
      affect the growth of. It did not inhibit the 1-deoxy-D-xylulose 5-phosphate
      reductoisomerase (DXR), but was converted by this enzyme into (3,4)-3,4,5
      trihydroxy-3-methylpentylphosphonic acid, an isosteric analogue of 2-C-methyl-D
      erythritol 4-phosphate. The enzyme was, however, less efficient with the
      methylene phosphonate analogue than with the natural substrate.

PMID- 14685308
TI  - Synthesis of rhamnosylated diosgenyl glucosides as mimetics of cytostatic
      steroidal saponins from Ornithogalum saindersiae and Galtonia candicans.
AB  - The synthesis of mimetic of the steroid saponins 1 and 2 was investigated. As a
      substitute for the complex 22-homo-23-nor-steroid moieties A and B in 1 and 2
      diosgenin was introduced. The silyl protected thioorthoester 20 was successfully
      employed for glucosylation. After selective 2--deacetylation, the glucosylated
      diosgenyl acceptor 23 was rhamnosylated. The 4---methoxybenzoylated donor 12 gave
      only minor yields. By using the tri--benzoyl protected donor 15 the [small alpha]
      -rhamnopyranosyl-(1[rightward arrow]2)-[small beta]--glucopyranosyl-(1[rightward
      arrow]3[small beta])-diosgenin derivative 25 was obtained.

PMID- 14685309
TI  - Demethylation of 2,4-dimethoxyquinolines: the synthesis of atanine.
AB  - The synthesis of the quinoline alkaloid atanine 6, by selective demethylation of
      the 2,4-dimethoxyquinoline 11 is presented. An alternative demethylation
      utilising a thiolate anion leads to the regioisomeric 4-hydroxyquinoline 13.

PMID- 14685310
TI  - Efficient synthesis of (-)- and (+)-tricyclic compounds with enone
      functionalities in rings A and C. A novel class of orally active anti
      inflammatory and cancer chemopreventive agents.
AB  - Novel tricyclic compounds with enone functionalities in rings A and C [tricyclic
      bis-enone (TBE) compounds] were designed on the basis of the structure of a
      synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid
      (CDDO)(1), which is a promising drug candidate for prevention and/or treatment of
      cancer and inflammatory diseases whose pathogenesis may involve excessive
      production of nitric oxide (NO) and/or prostaglandins. A series of TBE compounds
      in racemic form shows high inhibitory activity against production of NO induced
      by interferon-[gamma](IFN-[gamma]) in mouse macrophages. One of these compounds,
      (+/-)-(4a[small beta],8a[small beta],10a[small alpha])-1,2,4a,6,8a,9,10,10a
      octahydro-1,1,4a,8a-tetramethyl-2,6-dioxophenanthrene-3,7-dicarbonitrile ((+/-)
      3), is orally active at 15 mg kg(-1)(single administration) in a preliminary
      study using mouse peritoneal inflammation induced by thioglycollate and IFN
      [gamma]. Therefore, we desired to synthesize optically active TBE compounds for a
      comparison of the biological potency of both enantiomers. We now describe the
      synthesis of both enantiomers of (4a[small beta],8a[small beta],10a[small alpha])
      1,2,4a,6,8a,9,10,10a-octahydro-1,1,4a,8a-tetramethyl-2,6-dioxophenanthrene-3
      carbonitrile (2) and 3 from commercially available simple compounds.
      Interestingly, (+)-3 having the same configuration as the CDDO antipode shows
      about 10 times higher inhibitory activity than (-)-3 on NO production in mouse
      macrophages. In contrast, (-)-3 inhibits proliferation of MCF-7 breast cancer
      cells, whereas (+)-3 does not.

PMID- 14685311
TI  - Polymer-assisted solution phase synthesis of the antihyperglycemic agent
      Rosiglitazone (Avandia).
AB  - The commercially important antihyperglycemic agent Rosiglitazone 1(Avandia) has
      been prepared in high purity by a multi-step, polymer-assisted solution phase
      (PASP) synthesis without the need for the conventional chromatographic
      purification of any intermediates.

PMID- 14685312
TI  - Remarkable effect of 2[small alpha]-modification on the VDR antagonistic activity
      of 1small alpha-hydroxyvitamin D3-26,23-lactones.
AB  - Novel 2[small alpha]-methyl-, 2[small alpha]-(3-hydroxypropyl)- and 2[small
      alpha]-(3-hydroxypropoxy)-substituted 25-dehydro-1[small alpha]-hydroxyvitamin D
      26,23-lactone derivatives were efficiently synthesized Reformatsky type
      allylation and palladium-catalyzed alkenylative cyclization processes, and their
      biological activities were evaluated. Introducing functional groups into the
      2[small alpha]-position of the vitamin D-26,23-lactones resulted in remarkable
      enhancement of their antagonistic activity on vitamin D receptor (VDR).

PMID- 14685313
TI  - Reaction of [60]fullerene with free radicals generated from active methylene
      compounds by manganese(III) acetate dihydrate.
AB  - The reaction of [60]fullerene with dimethyl malonate and diethyl malonate in the
      presence of manganese(III) acetate dihydrate (Mn(OAc)3.2H2O) for 20 min afforded
      singly bonded [60]fullerene dimers 1a and 1b in a 1,4-addition pattern. When the
      reaction time was extended to 1 h, 1,4-bisadducts 2a and 2b were obtained.
      Unsymmetrical 1,4-adduct 5 and C2 symmetrical 1,16-bisadduct 6 were obtained when
      diethyl bromomalonate was used as the active methylene compound. Reaction of
      [60]fullerene with malononitrile and ethyl cyanoacetate with the aid of
      Mn(OAc)3.2H2O produced methanofullerenes 7 and 8. It is proposed that all these
      products were formed the addition of free radicals from the active methylene
      compounds generated by Mn(OAc)3.2H2O.

PMID- 14685314
TI  - Directed evolution of enzymes: new biocatalysts for asymmetric synthesis.
AB  - Directed evolution has been employed to generate new enzymes for the
      deracemisation of chiral amines.

PMID- 14685315
TI  - Structure-based design of carboxybiphenylindole inhibitors of the ZipA-FtsZ
      interaction.
AB  - Structural features of two weak inhibitors of the ZipA-FtsZ protein-protein
      interaction which were found to bind to overlapping but different areas of the
      key binding site were combined in one new series of carboxybiphenyl-indoles with
      improved inhibitory activity.

PMID- 14685316
TI  - Solid-phase synthesis and characterization of a novel fullerene-peptide derived
      from histone H3.
AB  - A peptide analogue from a histone H3 protein containing the L-fulleropyrrolidino
      glutamic acid has been prepared by a solid-phase approach and has been fully
      characterized. By molecular modelling it was verified that this peptide
      derivative is able to retain a binding capacity to the MHC (major
      histocompatibility complex) molecule similar to that of the cognate epitope.

PMID- 14685317
TI  - Heterologous expression in Saccharopolyspora erythraea of a pentaketide synthase
      derived from the spinosyn polyketide synthase.
AB  - A truncated version of the spinosyn polyketide synthase comprising the loading
      module and the first four extension modules fused to the erythromycin
      thioesterase domain was expressed in Saccharopolyspora erythraea. A novel
      pentaketide lactone product was isolated, identifying cryptic steps of spinosyn
      biosynthesis and indicating the potential of this approach for the biosynthetic
      engineering of spinosyn analogues. A pathway for the formation of the tetracyclic
      spinosyn aglycone is proposed.

PMID- 14685318
TI  - Carbohydrate-protein interactions at interfaces: comparison of the binding of
      Ricinus communis lectin to two series of synthetic glycolipids using surface
      plasmon resonance studies.
AB  - Two C-lactosyl lipids and the related C-galactosyl lipids have been synthesised
      and their binding to RCA120 plant lectin was compared with a second series of
      thiolactosylethoxyalkanes. The interactions were measured quantitatively in real
      time by surface plasmon resonance (BIAcore) at a range of concentrations and
      temperatures from 5 to 30 degrees C. The C-galactosyl lipid (1,3-dimethyl-5-[beta
      D-galactopyranosyl]-5-(4-octadecyloxybenzyl)pyrimidine-2,4,6-trione) bound much
      more weakly with a K(A) = 8.86 x 10(5) than the corresponding C-lactosyl lipid
      (1,3-dimethyl-5-[beta-D-galactopyranosyl-(1 --> 4)-beta-D-glucopyranosyl]-5-(4
      octadecyloxybenzyl)pyrimidine-2,4,6-trione) (K(A) = 2.31 x 10(7)). The influence
      of the linker region of the two different series of lactosyl lipids was clearly
      demonstrated by the differences in the binding to RCA120 lectin. The changes in
      kinetic values and in the enthalpic and entropic contribution to the free energy
      of binding reflected the importance of the linker and the hydrocarbon anchor
      holding the synthetic glycolipids in the neomembrane.

PMID- 14685319
TI  - A novel strategy towards the synthesis of orthogonally functionalised 4
      aminoglycosides.
AB  - A tethered nucleophilic substitution strategy for the stereoselective
      introduction of axially oriented amino functions on suitably protected gluco- and
      mannopyranosides is presented. The obtained oxazine is a versatile building
      block, which after some manipulation, could be used in the construction of highly
      functionalised oligosaccharides.

PMID- 14685320
TI  - The syntheses of tricyclic analogues of O6-methylguanine.
AB  - The syntheses of the novel pyrrolo[2,3-d]pyrimidine-based heterocycles as
      tricyclic analogues of O6-methylguanine are described. Compound 5 is a weak
      inhibitor of human O6-alkylguanine DNA alkyltransferase.

PMID- 14685321
TI  - Total synthesis of (+)-phorboxazole A, a potent cytostatic agent from the sponge
      Phorbas sp.
AB  - A convergent total synthesis of phorboxazole A (1a), from the C(3-19), C(20-27)
      and C(33-46) fragments 5, 4 and 91, respectively, concentrating on
      stereocontrolled formation of the bonds at C(2-3), C(19-20) and C(27-28), is
      described. Although a coupling reaction between a macrolide ketone and the side
      chain substituted sulfone, at C(27-28) was not successful, a Wadsworth-Emmons
      olefination involving the oxane methyl ketone 4 and an oxazole produced the oxane
      90 which was next coupled to 91 leading to the C(20-46) unit 100. A further
      coupling of 100 to 71c at C(19-20) then led to 105, ultimately, and the synthesis
      was completed by a macrocyclisation reaction from 105, at the C(2-3) alkene bond,
      followed by deprotection of 106.

PMID- 14685322
TI  - Efficient syntheses of pterulone, pterulone B and related analogues.
AB  - An efficient synthesis of the three halogenated naturally occurring products,
      pterulone (2), pterulone B (3) and alcohol 5, and of a wide range of related
      unnatural analogues has been achieved starting from the two readily available 1
      benzoxepine sulfonyl-containing intermediates 6a and 6b. The biological
      activities of pterulone and some of the synthesized analogues were tested against
      a wide spectrum of phytopathogenic fungi.

PMID- 14685323
TI  - Synthesis and molecular structure of new acyclic analogues of nucleotides with a
      1,2-alkadienic skeleton.
AB  - Reaction of 1-chloro-4-(diethoxyphosphonyl)alka-2,3-dienes 14,15 with purine and
      pyrimidine heterocyclic bases in the presence of cesium carbonate afforded new
      acyclic analogues of nucleotides containing a 1,2-alkadienic skeleton 18-23.
      Dealkylation of 18-23 furnished phosphonic acids 2a-f. In contrast, alkylation
      reaction with 1-chloro-4-(diethoxyphosphonyl)octa-2,3-diene 16 led to Z- and E
      1,3-alkadienic phosphonates 25a,b and 26a,b. A similar reaction with 1-chloro-4
      (diethoxyphosphonyl)-2-methylbuta-2,3-diene 17 led to the elimination of
      hydrochloride and formation of 4-(diethylphosphonyl)-2-methylbut-1-en-3-yne 24.
      Molecular structures of new acyclic nucleotides 18 and 2f are determined by X-ray
      crystallographic analysis.

PMID- 14685324
TI  - Synthesis of regioisomeric analogues of crisamicin A.
AB  - The synthesis of bis-furonaphthopyrans 12a and 12b, regioisomeric analogues of
      the dimeric pyranonaphthoquinone antibiotic crisamicin A 1 is described. The key
      intermediate 16 was prepared via a one-pot in situ Suzuki-Miyaura homocoupling of
      naphthyl triflate 23 using bis(pinacolato)diboron. Oxidation of binaphthyl 16 to
      bis-naphthoquinone 14 was then effected with silver(II) oxide and nitric acid.
      Efficient double furofuran annulation of bis-naphthoquinone 14 with 2
      trimethylsilyloxyfuran 8 afforded bis-furonaphthofuran adducts 13a and 13b as an
      inseparable 1:1 mixture of diastereomers. Oxidative rearrangement of this mixture
      of bis-furonaphthofuran adducts 13a and 13b using silver(II) oxide and nitric
      acid afforded unstable bis-furonaphthopyrans 12a and 12b also as a 1:1 mixture of
      diastereomers. Addition of 2-trimethylsilyloxyfuran 8 to naphthoquinone 25
      afforded adduct 26 that underwent oxidative rearrangement to furonaphthopyran 27,
      however attempts to effect Suzuki-Miyaura homocoupling of triflates 26 and 27 to
      their respective dimers 13 and 12, was unsuccessful.

PMID- 14685325
TI  - Exploring the active site of human factor Xa protein by NMR screening of small
      molecule probes.
AB  - A collection of small molecules (MW < 350 Da) was screened for binding to human
      factor Xa using saturation transfer difference NMR spectroscopy to detect
      binding. The NMR screening experiments identified four hits. Binding isotherms
      constructed from NMR linewidth data showed that the binding affinities of the
      hits were all in the 30-210 microM range. Competition binding experiments showed
      that three of the ligands were displaced by a known microM inhibitor of factor
      Xa. The success of the method for identifying new ligands and the relevance of
      this information to the design of new factor Xa inhibitors are discussed.

PMID- 14685326
TI  - Selective recognition of thymidylylthymidine (TpT) and antitumor effects of a
      macrocyclic dizinc(II) complex.
AB  - A polyamino dizinc(II) complex, [(N-bisdien)Zn2(II)Cl2](ClO4)2, (LZn), has been
      synthesized as a new nucleobase receptor molecule in aqueous solution at
      physiological pH, and shows to be highly selective in recognizing deoxythymidine
      (dT) and thymidylylthymidine (TpT). The strong acidic Zn(II) ions in LZn at the
      fifth coordination sites interact with a variety of nucleosides. The binding and
      recognition processes have been studied by potentiometric titration. The X-ray
      crystal analysis of LZn shows that the two zinc ions are out of the basal plane
      of the macrocycle, favoring the effective recognition of TpT on the single strand
      of DNA. In vitro antitumor investigation shows that LZn is a patent inhibitor of
      tumor cell growth with IC50 values below 10 micromolar.

PMID- 14685327
TI  - Preparation and evaluation of sulfur-containing metal chelators.
AB  - With a view to probe the structure and function of G-protein coupled receptors
      the synthesis of functionalized 8-mercaptoquinoline derivatives and 2-(2
      pyridyl)thiophenol was achieved. A fluorescence-based method for determining the
      affinity of these metal chelators toward zinc ions was developed.

PMID- 14685328
TI  - Preparation of enantiomerically pure pyridyl amino acids from serine.
AB  - A range of substituted pyridyl amino acids have been prepared by palladium
      catalysed cross-coupling of serine-derived organozinc reagents with differently
      substituted halopyridines. Following this procedure a DMAP analogue has been
      synthesised and used as a building block in the preparation of two related
      tripeptides, which have been tested as catalysts in the kinetic resolution of
      trans-2-(N-acetylamino)cyclohexan-1-ol, resulting in modest enantioselectivity.

PMID- 14685330
TI  - Synthesis and chemistry of 3-tert-butyl-1,5-diaminopyrazole.
AB  - N-Amination of 3-amino-5-tert-butylpyrazole 11 with hydroxylamine-O-sulfonic acid
      gave the 1,5-diaminopyrazole 12 with good regiochemical control. The reactions of
      12 with certain electrophiles (e.g. acetic anhydride, DMF acetal, aromatic
      aldehydes, methoxymethylene Meldrum's acid) took place at one (or both) of the
      amino groups and no cyclised products were obtained. Reaction of 12 with carbon
      disulfide followed by alkylation under basic conditions provided the pyrazolo[1,5
      b]1,2,4-triazole 26 which is a useful photographic magenta coupler. Reactions of
      12 with 1,2- and 1,3-dicarbonyl compounds (diketones and ketoesters) provided new
      pyrazolo[1,5-b]1,2,4-triazines 29, 30, 42 and 43 and the first derivatives of the
      pyrazolo[1,5-b]1,2,4-triazepine system 31 and 35-36. The X-ray crystal structure
      of the pyrazolotriazepine 33 is reported.

PMID- 14685329
TI  - Cyclizative radical carbonylations of azaenynes by TTMSS and hexanethiol leading
      to alpha-silyl- and thiomethylene lactams. Insights into the E/Z
      stereoselectivities.
AB  - Free-radical mediated cyclizative carbonylations of azaenynes were carried out
      using TTMSS as a radical mediator to compare the efficiency and the
      stereochemistry with those using tributyltin hydride. Using a substrate
      concentration of 0.1 M, the reactions gave good yields of alpha-silylmethylene
      lactams having four to seven-membered rings. The observed E-diastereoselectivity
      of the resulting vinylsilane moiety is in sharp contrast to the Z-selectivity
      observed during the analogous carbonylation using tributyltin hydride. When
      hexanethiol was used as the radical mediator, alpha-thiomethylene lactams were
      formed with E-favoring stereoselectivity again. Ab initio and DFT molecular
      orbital calculations on the stability of E and Z products were carried out for a
      set of five-membered methylene lactams bearing SnH3, SiH3, and SMe groups. The
      distinct thermodynamic preference for the Z-isomer was only predicted for the Sn
      bearing lactam. A steric effect due to the bulky (TMS)3Si group is proposed for
      the E-selectivity observed in the TTMSS-mediated reaction.

PMID- 14685331
TI  - Highly diastereoselective addition of nitromethane anion to chiral alpha
      amidoalkylphenyl sulfones. Synthesis of optically active alpha-amino acid
      derivatives.
AB  - Optically active syn-alpha-amidoalkylphenyl sulfones can be prepared from chiral
      aldehydes in anhydrous conditions using benzenesulfinic acid. These sulfones in
      basic conditions give N-acylimines that react with sodium methanenitronate to
      afford the corresponding nitro adducts with high anti diastereoselectivity. PM3
      semiempirical calculations provide a rationale for the observed opposite
      stereoselectivity. The obtained nitro derivatives undergo a Nef reaction followed
      by a methylation giving optically active beta-hydroxy-alpha-amino acid and
      alpha,beta-diamino acid esters in good yield. These amino acid derivatives are
      important building blocks for the preparation of biologically active compounds.

PMID- 14685332
TI  - Intramolecular addition of benzylic radicals onto ketenimines. Synthesis of 2
      alkylindoles.
AB  - The inter- and intramolecular addition of free radicals onto ketenimines is
      studied. All the attempts to add intermolecularly several silicon, oxygen or
      carbon centered radicals to N-(4-methylphenyl)-C,C-diphenyl ketenimine were
      unsuccessful. In contrast, the intramolecular addition of benzylic radicals,
      generated from xanthates, onto the central carbon of a ketenimine function with
      its N atom linked to the ortho position of the aromatic ring occurred under a
      variety of reaction conditions. These intramolecular cyclizations provide a novel
      radical-mediated synthesis of 2-alkylindoles.

PMID- 14685333
TI  - Enantioselective synthesis of epoxides by alpha-deprotonation--electrophile
      trapping of achiral epoxides.
AB  - Enantioselective alpha-deprotonation of achiral epoxides 1, 21, and 26 using
      organolithiums in the presence of (-)-sparteine 2 and subsequent electrophile
      trapping gives access to enantioenriched trisubstituted epoxides 9-17, 22, 23, 27
      and 28 (in up to 86% ee).

PMID- 14685334
TI  - Alpha-oximono-esters as precursors to heterocycles--generation of oxazinone N
      oxides and cycloaddition to alkene dipolarophiles.
AB  - Preparation of a series of terminally and internally substituted delta-alkenyl
      and delta-alkynyl esters 6, 7 and 9, potential precursors to oxazin-2-one
      nitrones, has been attempted. Condensation between pyruvic or benzoylformic acid
      and the appropriate alcohol proceeded smoothly in some cases whilst allylic
      transposition was a major feature in other cases--most especially during
      reactions with alpha-vinylbenzyl alcohol. Oximation of pyruvic acid derivatives
      furnished E-oxime isomers whilst benzoylformic acid derivatives afforded mixed
      geometrical isomers. The E-oxime of 4a1 carrying an internal Me group undergoes
      facile thermal cyclisation affording nitrones 1c and 1d in good yield. Oximes E
      5a,b with a terminal methyl substituent on the alkene moiety furnish nitrone only
      under the influence of an external electrophile [PhSeBr/AgBF4]. A terminal Ph
      substituent on 5c,d prohibits formation of the cyclic dipole irrespective of
      reaction conditions, and whilst 5d reacts to afford a bicyclic isoxazolofuranone
      13 by an IOOC reaction (intramolecular oxime olefin cyclisation) 5c remains
      thermally inert. Finally delta-alkynyl oximes 9c,d also failed to cyclise. The
      regio- and stereochemical characteristics of the cycloadditions between the new
      dipoles and electron poor olefinic dipolarophiles have been investigated. The
      conditions needed for reaction were rather forcing since the dipoles are somewhat
      stabilised by the adjacent alkoxycarbonyl group. All reactions proceeded
      regiospecifically to give adducts with 5-substituted isoxazolidine rings whilst
      diastereoselectivity varied with the choice of dipolarophile and the steric
      demands of the nitrone substituents. The phenylselenyl dipole 10a could not be
      trapped by any dipolarophiles bar dimethyl acetylenedicarboxylate.

PMID- 14685335
TI  - Evaluation of sulfur, selenium and tellurium catalysts with antioxidant
      potential.
AB  - Oxidative stress is implicated, either directly or indirectly, in the pathology
      of a range of human diseases. As a consequence, the development of efficient
      antioxidants for medical use has become increasingly important. We have
      synthesised a range of structurally related organo-sulfur, -selenium and 
      tellurium agents and demonstrated that a combination of electrochemical
      methodology, in vitro assays and cell culture tests can be used to rationalise
      the antioxidant activity of these catalytic agents. Based on its exceptionally
      low anodic oxidation potential (Epa) and high activity against the representative
      oxidative stressors tert-butyl hydroperoxide and peroxynitrite, 4,4'
      dihydroxydiphenyltelluride is predicted to be a potent antioxidant. This compound
      exhibits a correspondingly high activity with a remarkably low IC50 value of 20
      nM, when tested in PC12 cell culture using a bioassay indicative of the early
      stages of Alzheimer's disease.

PMID- 14685336
TI  - Understanding the mechanism of base-assisted decomposition of (N-halo),N
      alkylalcoholamines.
AB  - The base-assisted decomposition of (N-X),N-methylethanolamine (X = Cl, Br) takes
      place mainly through two concurrent processes: a fragmentation and an
      intramolecular elimination. The global process follows second order kinetics,
      first order relative to both (N-X),N-methylethanolamine and base. Interaction of
      the base with the ionizable hydroxylic hydrogen triggers the reaction. The
      intramolecular elimination pathway leads to formaldehyde and 2-aminoethanol as
      reaction products via base-assisted proton transfer from the methyl to the
      partially unprotonated hydroxylic oxygen, with loss of halide. Meanwhile, the
      fragmentation pathway leads to methylamine and two equivalents of formaldehyde
      via bimolecular base-promoted concerted breakage of the molecule into
      formaldehyde, halide ion and N-methylmethanimine. Kinetic evidences allow a crude
      estimation of the concertedness and characterization of the transition structure
      for both processes, which are slightly asynchronous, the proton transfer to the
      base taking place ahead of the rest of the molecular events. The degree of
      asynchroneity increases as the bases become weaker. Electronic structure
      calculations, at the B3LYP/6-31++G** level, on the fragmentation pathway support
      the proposed mechanism.

PMID- 14685337
TI  - Thermochemical study of the ethylpyridine and ethylpyrazine isomers.
AB  - The standard (p(o) = 0.1 MPa) molar energies of combustion in oxygen, at T =
      298.15 K, of four liquids: 2-ethylpyridine, 4-ethylpyridine, ethylpyrazine and
      2,3-diethylpyrazine were measured by static bomb calorimetry in an oxygen
      atmosphere. The values of the standard molar enthalpies of vaporization, at T =
      298.15 K, were obtained by Calvet microcalorimetry, allowing the calculation of
      the standard molar enthalpies of formation of the compounds, in the gas phase, at
      T= 298.15 K: 2-ethylpyridine (79.4 +/- 2.6) kJ mol(-1); 4-ethylpyridine (81.0 +/-
      3.4) kJ mol(-1); ethylpyrazine (146.9 +/- 2.8) kJ mol(-1); and 2,3
      diethylpyrazine (80.2 +/- 2.9) kJ mol(-1). The most stable geometries of all
      ethylpyridine and ethylpyrazine isomers were obtained using the density
      functional theory with the B3LYP functional and two basis sets: 6-31G* and 6
      311G**. These calculations were then used to obtain estimates of the enthalpies
      of formation of all isomers, including those not experimentally studied, through
      the use of isodesmic reactions. A discussion of the relationship between
      structure and energetics of the isomers is also presented.

PMID- 14685338
TI  - An ab-initio study of some homolytic substitution reactions of acyl radicals at
      silicon, germanium and tint.
AB  - Ab initio calculations using the 6-311G**, cc-pVDZ, and (valence) double-zeta
      pseudopotential (DZP) basis sets, with (MP2, QCISD, CCSD(T)) and without (UHF)
      the inclusion of electron correlation, and density functional (BHandHLYP, B3LYP)
      calculations predict that homolytic substitution reactions of acetyl radicals at
      the silicon atoms in disilane can proceed via both backside and frontside attack
      mechanisms. At the highest level of theory (CCSD(T)/cc-pVDZ//MP2/cc-pVDZ), energy
      barriers (deltaE double dagger) of 77.2 and 81.9 kJ mol(-1) are calculated for
      the backside and frontside reactions respectively. Similar results are obtained
      for reactions involving germanium and tin with energy barriers (deltaE double
      dagger) of 53.7-84.2, and 55.0-89.7 kJ mol(-1) for the backside and frontside
      mechanisms, respectively. These data suggest that both homolytic substitution
      mechanisms are feasible for homolytic substitution reactions of acetyl radicals
      at silicon, germanium, and tin. BHandHLYP calculations provide geometries and
      energy barriers for backside and frontside transition states in good agreement
      with those obtained by traditional ab initio techniques.

PMID- 14685339
TI  - On benzo[b][1,4]diazepinium-olates, -thiolates and -carboxylates as anti-Huckel
      mesomeric betaines.
AB  - 2,3-Diaminophenol 4, 3,4-diaminophenol 5, 4-methoxy-1,2-diaminobenzene 6, 3,4
      diaminobenzenethiol 7, 2,3-diaminobenzoic acid 8, and 3,4-diaminobenzoic acid 9
      were reacted with 2,4-pentanedione to yield the corresponding
      benzo[b][1,4]diazepinium salts, respectively. The hydroxy
      benzo[b][1,4]diazepinium salts 17 and 18 do not form mesomeric betaines (MB) on
      deprotonation. Instead, they are converted into the diimines 24 and 25. By
      contrast, the 7-mercaptobenzo[b][1,4]diazepinium salt 20 yields the corresponding
      thiolate on increasing the pH of the solution. This MB, which possesses 4n pi
      electrons, does not fit into the classification system of heterocyclic mesomeric
      betaines accepted today. Deprotonation of the betaine results in the formation of
      an instable anionic thiolate 31 which oxidizes immediately to the disulfide 32.
      The carboxy derivatives 21 and 22 readily form cross-conjugated mesomeric
      betaines. Whereas the diimine 34 proved to be instable, the sodium salt of the
      diimine 36 was unambiguously characterized. An X-ray single crystal analysis of
      22 as its picrate is presented in order to gain additional insights into these 4n
      pi-electron systems.

PMID- 14685340
TI  - Self-organization of lactates in the gas phase.
AB  - Chiral recognition and subsequent selective self-organisation into hydrogen
      bonded n-mers is observed in supersonic methyl lactate expansions. The nu(OH) and
      nu(C=O)-vibrations are investigated by ragout-jet FTIR-spectroscopy and lead to
      the assignment of homo- and heterochiral clusters of at least three different
      cluster sizes. Whereas homo- and heterochiral dimers are formed in similar
      amounts in the racemic mixture, prominent absorptions due to different homochiral
      and heterochiral lactate trimers and tetramers indicate highly specific chiral
      self-recognition beyond molecular pairs. Chemical modification of the ester-group
      (methyl-, ethyl- and isopropyl-lactate) and argon admixture to the helium
      expansion contribute importantly to an understanding of the cluster spectra and
      topology.

PMID- 14685341
TI  - [Liver transplantation from living related donors: ethical aspects]

PMID- 14685342
TI  - [Fecundity in adolescence: historical and current perspectives]

PMID- 14685343
TI  - [The importance of oxygen free radicals in the neonatal period]
AB  - OBJECTIVE: Oxygen free radicals are extremely reactive species and they can lead
      to injury and cell death. The aim of this review is to study the main biochemical
      aspects of free radical formation and their role as an intermediate mechanism of
      injury in several neonatal diseases.METHODS: A brief history of oxygen therapy in
      neonatology and its relationship with complications associated with the
      production of free radicals. Definition, mechanism of action and antioxidant
      systems were described. Next, the neonatal factors of increased risk of free
      radical oxidative injury and the diseases associated with oxygen free radical
      toxicity were reviewed.RESULTS: Oxygen free radicals are reactive species that
      although crucial to normal biological processes, can lead to injury and cell
      death. They are implicated in the pathogenesis of many neonatal diseases such as
      perinatal asphyxia, bronchopulmonary dysplasia, retinopathy of prematurity,
      necrotizing enterocolitis, intracranial hemorrhage, pulmonary hypertension and
      persistence of ductus arteriosus. Birth is associated with transition to a
      hyperoxic environment in comparison with uterine environment, which leads to
      increased generation free radicals. The newborn has undeveloped antioxidant
      systems and, therefore, may be at increased risk of free radical oxidative
      injury.CONCLUSIONS: The understanding of neonatal factors involved in the
      pathogenesis of "oxygen free radical diseases" will lead to the development of
      new therapies for prevention and treatment of these neonatal diseases.

PMID- 14685344
TI  - [Liver transplantation from living related donors]
AB  - OBJECTIVES: To present the experience with the first 12 living related liver
      transplants performed at Hospital Sirio-Libanes in Sao Paulo. METHODS: The donors
      were the fathers (6) and the mothers (6) with age ranging from 30 to 48 years.
      All candidates for donation were submitted to a full informed consent form,
      clinical and radiological evaluation and had blood withdrawn for autotransfusion.
      Recipient age ranged from 7 months to 10 years whereas recipient weight varied
      from 6.3 to 34 kg. Six patients were considered as high risk due to complications
      of advanced liver disease and were submitted to urgent transplantation. RESULTS:
      Mean donor hospital stay was 10 days with no mortality. Technical complications
      were observed in 4 recipients. Seven patients presented at least one episode of
      bacterial, viral or fungal infection. One or more biopsy proven rejection
      episodes were disclosed in 7 patients. Overall recipient survival was 67%, being
      83% for elective cases and 50% for urgent cases. Long term follow up ranged from
      8 to 25 months. Seven out of 8 survivors present excellent quality of life and
      normal liver function. The other patient is currently under reduced
      immunosuppression due to Epstein-Barr virus infection.CONCLUSIONS: These results
      demonstrate the safety and viability of living related liver transplantation
      which, in face of the current donor scarcity, should be considered as a valid
      option for the treatment of children with end stage liver disease.

PMID- 14685345
TI  - [Is adolescent pregnancy a risk factor for low birth weight?]
AB  - OBJECTIVE: This paper was designed to study the pregnancy in adolescence as a
      risk factor for low birth weight.METHODOLOGY: A case-control study was designed,
      including 354 mothers whose babies' weight was less than 2.5 kg and another group
      of the same size, with babies of 3.0 kg or more. All deliveries took place at
      Maternidade de Campinas, and all mothers were interviewed and compared. Besides
      mother's age, other variables that could offer risk of low birth weight were also
      evaluated. A multiple logistic regression analysis was applied, to control
      possible influences of these variables.RESULTS: Adolescents accounted for 22.9%
      of the mothers whose babies had low birth weight. The risk of low birth weight
      among this group (OR=0.72; 95%IC=0.45-1.14; p=0.16) was not considered greater
      when compared with that of mothers between 20 and 34 years old (before and after
      correction for income, marital status, educational level, race, previous
      pregnancies, prenatal assistance, exposure to smoking and caffeine, arterial
      hypertension, weight prior to pregnancy and employment). Complementary analysis
      showed that pregnancy in adolescence is a protection factor against intrauterine
      growth retardation (OR=0.24; 95%IC =0.10-0.56; p= 0.001).CONCLUSION: In this
      population, pregnancy in adolescence did not represent a greater risk for
      occurrence of low birth weight, when others factors like psychosocial, pre
      gestational risks, smoking and poor prenatal care were controlled for.

PMID- 14685346
TI  - [Relationship between maternal weight gain and birthweight]
AB  - OBJECTIVE: To investigate the influence of gestational weight gain on birthweight
      of the newborn, in order to clarify if this weight increment results in heavier
      newborn. METHODS: Retrospective cohort in a tertiary level private institution
      that attends a high income population of Sao Paulo - Brazil; inclusion of all the
      mother-newborn pairs with complete data (2275) in the Cadastro de Informacoes
      Perinatais (CIP) in the software EPI 6; from February/95 till June/96.RESULTS:
      Gestational weight gain between 12 and 20 kg resulted in a greater number of
      newborn with birthweights between 3000 and 3499g. Pregnancies with a weight gain
      below or equal 10 kg correlated with newborn of low birthweight (Odds ratio=
      1.81; CI= 1.20-2.73; 95% of significance). Gestational gain beneath or equal to
      12 kg had a greater risk of a newborn with insufficient weight - 2499<
      birthweight < 3000g - (Odds ratio= 1.47; CI= 1.19-1.81; 95% of significance).
      Gestational gain above 16 kg did not correlate with increase in
      birthweight.CONCLUSIONS: The gestational weight gain of 12 kg is the minimum
      increase of weight in order that the newborn is over 3000g. The gestational
      weight gain above 16 kg did not increase birthweight. The high social economic
      level was not sufficient to avoid low birthweight or insufficient weight at
      birth.

PMID- 14685347
TI  - [Hematuria in children: retrospective study of 128 pediatric patients]
AB  - OBJECTIVE: To evaluate the diagnostic frequency of the various diseases
      associated with the development of hematuria in children, in a pediatric
      nephrology unit pertaining to a university hospital. METHODS: The clinical
      records of 128 children (70 male, 50 female) who presented
      intermittent/persistent macroscopic hematuria or persistent microscopic hematuria
      as the chief clinical complaint/finding, in the period of 1978-1995, were
      retrospectively analyzed. This evaluation was performed with special attention to
      the patientacute;s clinical history, physical examination, personal and family
      morbid history information. Patients whose investigation was not complete were
      not considered for analysis. The mean age on presentation was 8.2 years (5 months
      - 16 years) and the mean period of observation was 3.2 years (1 month-15 years).
      RESULTS: Macroscopic hematuria occurred in 104 patients and persistent
      microscopic hematuria was present in 24 patients. Urinary metabolic disturbances
      and urinary lithiasis, alone or in association, were diagnosed in the majority of
      the patients (65.5%). Hypercalciuria was the urinary metabolic disturbance
      (90.1%) mostly detected, either alone (73.2%) or in association with
      hyperuricosuria (16.9%). A positive family history of lithiasis was reported in
      32.1% of the patients in which the diagnosis of lithiasis/urinary metabolic
      disturbance was confirmed. Glomerulopathies were diagnosed in 25% of the
      patients, with the predominance of post-infectious acute glomerulonephritis (11
      patients, 34%). In 6 children, the etiology of hematuria was not elucidated,
      despite extensive investigation, including renal biopsy.CONCLUSION: The authors
      present an algorithm for the diagnosis of hematuria in children and suggest that
      in cases of isolated hematuria, presenting without clinical clues to the possible
      etiology, laboratory investigation should be started with the evaluation of
      urinary metabolic disturbances / lithiasis.

PMID- 14685348
TI  - [Epstein-Barr virus infection in children with AIDS]
AB  - OBJECTIVE: The association of the HIV and Epstein-Barr virus infections has been
      reported in several studies, specially in children that present lymphocytic
      interstitial pneumonitis. The analysis of the incidence of Epstein-Barr virus
      infection was performed in children with AIDS, in those with AIDS with and
      without lymphocytic interstitial pneumonitis, comparing to children without HIV
      infection. METHODS: A cross-sectional study was performed with 60 children with
      AIDS and 54 children not infected by HIV, matched by sex and age, in the Hospital
      Infantil Joana de Gusmao in Florianopolis city, Santa Catarina State, Brazil,
      between June 1994 and June 1995. The selection of the cases followed the order of
      the consultation. The detection of antibodies against Epstein-Barr capsid antigen
      was performed by standard indirect immunofluorescence techniques and ELISA, and
      antibodies against nuclear antigen only by ELISA. The stage of the infection was
      defined according to serologic responses. RESULTS: Lymphadenopathy occurred in 59
      cases (98.3%), hepatomegaly in 51 (85.0%), splenomegaly in 46 (76.7%), recurrent
      bronchopneumonia in 41 (68.3%). Lymphocytic interstitial pneumonitis was observed
      in 21 cases (35.0%), 90.5% of which showed positive serologic reactions to EBV.
      The geometric mean of the IgG against capsid antigen titers was 1:439.5 in the
      cases group and 1:42.8 in the controls. The IgM against capsid antigen by
      indirect immunofluorescence techniques was positive in 16 (26.7%) of the 60 cases
      and only in one of the 53 controls (1.9%) (p=0.0002). The primary Epstein-Barr
      virus infection was evidenced with greater frequency in the children with AIDS
      (p<0.0001), as well as the reactivated infection (p=0.0745). CONCLUSIONS: The
      incidence of primary and reactivated Epstein-Barr virus infection was more
      frequent in the patients with AIDS. The primary and reactivated Epstein-Barr
      virus infection was observed in almost all of the patients with diagnosis of
      lymphocytic interstitial pneumonitis (90.5%).

PMID- 14685349
TI  - [Are mothers encouraged to identify the risk signs of diarrhea?]
AB  - OBJECTIVES: To acknowledge the mothers' perception of the diarrhea episode and
      their ability in identifying the signs of risk; to characterize, in the health
      services, at ambulatory level, the activities that stimulate a timely attention
      to the disease.METHODS: An inquiry was applied to a representative sample of 1026
      children under 5 years old who live in the pilot areas of Pernambuco selected to
      receive interference concerning diarrhea, and an interconnected transversal study
      in 14 health services: 11 health centres and 3 hospitals.RESULTS: A high
      proportion of the mothers of children with diarrhea give importance clinical
      manifestations that do not allow an early identification of dehydration. Only one
      fourth of them mentions dehydration as a complication. The mothers perception of
      the episode has a striking influence on the adopted conduct, particularly in the
      Metropolitan Area, in which, in the absence of preoccupation, no children were
      taken to the physician and a significant smaller proportion received care to
      hydration. In the health services, in general, collective educational programs
      are not the routine, the consult with the physician is limited to the main
      complaint, there is no post-consult with the nurses nor articulation with
      community health agents. Besides that, half of the mothers did not know the signs
      of dehydration.CONCLUSIONS: The findings of both the inquiry and the evaluation
      of the health services showed a quite critical situation: mother's little
      perception of the mothers of diarrhea worsening signs, as well as the
      insufficiency of these services concerning educational activities towards
      stimulating mothers to recognize and valorize them.

PMID- 14685350
TI  - [Cryptosporidiosis and persistent diarrhea]
AB  - OBJECTIVE: The association between cryptosporidiosis and persistent diarrhea has
      been studied in many countries. The aim of this study was to verify the incidence
      of this parasite in children with persistent diarrhea. Children infected or not
      with protozoan cryptosporidium were compared in relation to laboratory and clinic
      analysis.METHODS: Retrospective study in 70 inmate suckling at pediatrics
      hospital due persistent diarrhea, younger than 2 year, negative HIV, and other
      causes of diarrhea were ruled out. The duration of diarrhea, hospitalization,
      clinic modifications, preceding history of diarrhea, nutrition, d-xilosis and
      diet management were appraised.RESULTS: Criptosporidium sp was founded in 14
      (20%) sucking and it was more frequent between children younger than 3 months
      (13/57, 23%). The duration of hospitalization and diarrhea were similar in both.
      Malnutrition was been present in 91.5% of patients, 13/14 of infected
      cryptosporidium children and 51/56 of not infected. The diet management was
      similar in both. There was a tendency to underdose xilosis of infected patients;
      mainly at the first year of life (15.9 +/- 8.2 and 33.8 +/- 19.9 p=0.007).
      CONCLUSION: Cryptosporidiosis is frequent in children with persistent diarrhea.
      Nevertheless, the infected patients did not differ of others if we consider
      theirs clinics, prognosis and therapeutics characteristics.

PMID- 14685351
TI  - [Cervicofacial teratoma in neonates]
AB  - OBJECTIVE: To emphasize the importance of cervicofacial teratoma in neonates and
      review the pertinent literature.METHODS: The authors report a case of
      cervicofacial teratoma in a 30th week gestation male newborn, submitted to total
      surgical resection. The diagnosis was confirmed by routine histological
      examination.RESULTS: Prenatal diagnosis was realized by ultrasound. A cesarean
      section was performed and the newborn presented progressive respiratory failure
      due to the large cervical mass. In the second day of life, a surgical resection
      was performed, but the newborn succumbed shortly thereafter. A pathological
      examination confirmed an Immature Teratoma grade I.CONCLUSION: Despite the low
      incidence of the cervicofacial teratoma, which account for approximately 3% of
      all neonatal teratomas, the early prenatal diagnosis might be helpful for success
      of any surgical therapeutic procedure. This is the third related case in latino
      americana's literature.

PMID- 14685353
TI  - [Breastfeeding indicators: towards uniformization]

PMID- 14685352
TI  - [Krabbe disease (globoid cell leukodystrophy): a case report]
AB  - OBJECTIVE: The authors report a case of Krabbe disease.METHODS: The authors
      report a case of patient with motor deterioration and irritability in first
      months of life being suspected and confirmed the hypothesis of Globoid Cell
      Leukodystrophy through the subsidiary exams and enzymatic dosage.RESULTS: The
      case presented signs and symptoms compatible with the early onset type of Krabbe
      Disease, being confirmed by dosage of the enzyme galactosylceramide beta
      galactosidase in fibroblasts culture.CONCLUSIONS: The Krabbe Disease is a rare
      autosomal recessive disorder and the suspicion many times dont arrive to be
      lifted up, not arriving to the specialist for diagnostic. In spite of there not
      being specific treatment, the genetic orientation is necessary.

PMID- 14685354
TI  - [Periventricular-intraventricular hemorrhage]

PMID- 14685355
TI  - [Challenges in the approach to adolescents: confidentiality and contraceptive
      orientation]
AB  - OBJECTIVE: The article has the purpose of presenting some questions related to
      professional ethics and juridical aspects of the approach to sexuality in
      adolescence, as well as of offering a practical review of the approach and
      contraceptive methods used by adolescents.METHODS: The bibliographic review
      encloses national and international literature, as well as juridical orientation
      in specific questions related to Child and Adolescent Statute and Brazilian Penal
      Code.RESULTS: Among the aspects of the approach to adolescents, confidentiality
      is distinguished as one of the most important strategies, mainly when the topic
      is associated to questions related to sexuality. In Brazil, although adolescents
      have been contributing in an effective way to the increase in the fecundity rate,
      there is, legally speaking, a hiatus concerning the guarantee of the rights of
      adolescents and professionals in exercise of contraceptive practice.CONCLUSIONS:
      The challenge for the health professionals, particularly the pediatricians who
      deal with adolescents, is to collaborate on the consolidation of rules which
      regulate the orientation in reproductive health for adolescents, once Brazilian
      Penal Code is anachronous concerning the reality of sexual behavior and its
      possible consequences.

PMID- 14685356
TI  - [Breastfeeding indicators in the city of Feira de Santana, Bahia, Brazil]
AB  - OBJECTIVE: To evaluate breast-feeding indicators surveying current alimentary
      status of under- two-year-old children.METHODS: During Vaccinations day, on June
      15th, 1996, 3,898 mothers were interviewed in urban areas of Feira de Santana,
      Bahia, Brazil. The methodology proposed at WHO/CED/SER 91.14 was used. Rates were
      calculated for the appropriate age groups: breast-feeding exclusive and
      predominant, persistence of breast-feeding one and two years, median duration of
      breast-feeding, timely complemented breast-feeding, bottle-feeding and pacifiers
      utilization.RESULTS: The main results were exclusive breastfeeding rate of 45.6%,
      in children from 0-3 months old; breastfeeding medium duration of 9 months; and
      persistence of 45.4% of breastfeeding in children from 12-15 months old.
      CONCLUSIONS: These results pointed that children in Feira de Santana are
      benefitting from breast-feeding more than in other areas of Bahia and other
      states of the Brazilian Northeast reflecting correct orientation. The methodology
      revealed ease to applicate providing significant and replicable samples. Wider
      utilization of standardized methodologies will contribute to improve monitoring
      of breast-feeding indicators in Brazil.

PMID- 14685357
TI  - [Risk factors to periventricular-intraventricular hemorrhage in newborns weighing
      less than 2000g]
AB  - OBJECTIVE: To study the incidence and analyze risk factors to neonatal
      periventricular-intraventricular hemorrhage; to suggest a working protocol for
      diagnosis in newborns at risk.METHODS: This is a cohort prospective study
      including 120 out of 129 children weighing less than 2000g born from May 18 th,
      1994 to May 17 th,1995 at the Hospital das Clinicas da UFMG. The study group
      comprised 39 newborns with the ultrasound diagnosis of periventricular
      intraventricular hemorrhage; the control group comprised 81 newborns who although
      submitted to the same evaluation protocol did not show any echographic signs of
      hemorrhage. The ultrasound examinations were all done by the same researcher who
      was not aware of the clinical history or the neurologic and laboratory
      examinations. The hemorrhage was classified according to Papiles criteria: grade
      I (13%); grade II (7%); grade III (9%) and grade IV (3%).RESULTS: Low gestational
      age, low birth weight, masculine sex, vaginal delivery, and neonatal sepsis were
      significantly associated (p < 0.05) with periventricular-intraventricular
      hemorrhage in univariate analysis. Apgar score in the first or fifth minute and
      Battaglias and Lubchenkos classification for the weight in relation to
      gestational age were not predisposing factors to the hemorrhage. Low gestational
      age (p = 0.002), vaginal delivery (p = 0.037), and masculine sex (p = 0.016) kept
      statistical significance after multivariate adjustment. Birth weight may
      substitute for gestational age in the multivariate model because they are highly
      associated. The best cutoff point to screen for periventricular-intraventricular
      hemorrhage was 1750 g instead of the traditionally adopted point of 1500 g.
      CONCLUSIONS: The incidence of neonatal periventricular-intraventricular
      hemorrhage was similar to those reported by other studies. Low gestational age or
      low birth weight, vaginal delivery and masculine sex were the most important risk
      factors to the hemorrhage. The screening cutoff point of 1750 g seems to be more
      adequate than the commonly used birth weight of 1500 g.

PMID- 14685358
TI  - [The unreliability of neurologic examination in the diagnosis of neonatal
      periventricular-intraventricular hemorrhage]
AB  - OBJECTIVE: To evaluate the efficacy of the clinical neurologic examination,
      hematocrit and glycemia in the diagnosis of periventricular-intraventricular
      hemorrhage in the newborn weighing less than 2000g considering the
      neurosonography as the gold standard.METHODS: This is a cohort prospective study
      from May 18th, 1994 to May 17th, 1995 carried out at the Hospital das Clinicas da
      UFMG. The study group comprised 38 newborns with the ultrasound diagnosis of
      periventricular-intraventricular hemorrhage; the control group comprised 81
      newborns who although submitted to the same evaluation protocol did not show any
      echographic signs of hemorrhage. The ultrasound examinations were all done by the
      same researcher who was not aware of the clinical history or the neurologic and
      laboratory examinations.RESULTS: Clinical neurologic alterations, mainly
      generalized hypotonia, were found to be associated with hemorrhage (p = 0.009),
      but there was a confounding effect due to the gestational age of the newborn. The
      predictive values of a positive or negative test were only 45% and 79%,
      respectively, which is clearly unreliable for the diagnosis of the hemorrhage.
      Hematocrit and glycemia were not clinically relevant either.CONCLUSIONS: The
      clinical neurologic examination is not reliable to indicate periventricular
      intraventricular hemorrhage in the newborn. Newborns at risk should be routinely
      screened by neurosonography.

PMID- 14685359
TI  - [Prognosis and evolution of bilateral grade III intraventricular - hemorhages
      (III-III-IVH)]
AB  - OBJECTIVE: To describe the evolution of bilateral III IVH so as to define optimal
      dates for therapeutic moves.METHODS: Longitudinal study of brain ultrasound scans
      from day 1 over the first three months of life. Our team calls "massive III" a
      hemorrhage with an intraventricular clot diameter >8mm on the coronal view at the
      level of Monro's foramina of the day of maximal hemorrhage. The 90 neonates were
      divided into four groups. Group I included 29 premature neonates who died in the
      first seven days after birth (birthweight (BW), 1,114 -/+253 g, gestational age
      (GA), 28 weeks 3 days); with 21 massive uni/bilateral grade III PIVH, and early
      filling of the whole ventricular system and cisterna magna. Group II included
      seven premature neonates who died in the second week after birth (similar in BW
      and GA, but more heterogeneous group). Two groups of infants survived for more
      than 14 days. Group III included 30 premature neonates (BW, 1,299 -/+260 g, GA,
      29 weeks 1 day), with 20 classical grade III PIVH, who had post-hemorrhagic
      dilatation regressed spontaneously in 13 cases and regressed after acetazolamide
      treatment in 17 cases (five deaths due to three bronchopulmonary dysplasias and
      two periventricular leucomalacias). Group IV included 24 premature neonates (BW,
      1,344 -/+289 g, GA, 29 weeks 5 days) with 15 massive grade III PIVH, who suffered
      posthemorrhagic hydrocephalus through obstruction of the Sylvius aqueduct (15)
      and/or of the cisterna magna (21), 12 blocks affecting both levels. Blocks were
      observed from day 8, and 35 in the quasi totality of cases (17
      deaths).CONCLUSIONS: From 1,183 consecutive peri-intraventricular hemorrhages
      (PIVH) diagnosed by brain ultrasound studies (01/01/81-12/31/94), 90 were grade
      (III-III) PIVH, with a 36% overall survival. The massive volume of grade III PIVG
      plays a heavy role in early deaths of extremely low birthweight neonates and it
      heralds a blocked hydrocephalus in more vigorous infants who survive PIVH.

PMID- 14685360
TI  - [Upper gastrointestinal endoscopy in children: indications and results]
AB  - OBJECTIVE: To present and discuss the indications, the endoscopic and histologic
      findings and the complications of upper digestive endoscopies carried out in
      children and adolescents.METHODS: We have done 228 endoscopies in pediatric
      patients with ages between 3 months to 19 years (x=5.7 y) during a period of 8
      months. General anesthesia was used in 80% of patients (182). Biopsies were done
      in 210 patients and the Helicobacter pylori was searched for in 130 patients by
      antral biopsies with Hematoxylin-Eosin coloration.RESULTS: The endoscopy
      indication was diagnostic in all patients, and in 18 cases there was some
      therapeutic procedure. Fifty-eight percent of examinations presented endoscopic
      alteration and 84% had abnormal histologic findings. The most frequent endoscopic
      findings were esophagitis in 50 patients, gastritis in 44 and duodenitis in 29.
      Ten peptic ulcers were diagnosed. Between the histologic findings the most
      frequent ones were gastritis in 87 patients, esophagitis in 50 and atrophy of
      duodenal mucosa in 9. The H. pylori was positive in 25 (19.2%)
      patients.CONCLUSION: The upper digestive endoscopy has become an essential
      procedure to the pediatric gastroenterology practice, amplifying the available
      diagnostic means and enabling therapeutic endoscopy in the presence of upper
      digestive lesions. In the present report, 58% of the studied population presented
      some endoscopic lesion.

PMID- 14685361
TI  - [Etiological profile of bacterial meningitis in a small hospital]
AB  - OBJECTIVE: To determine the etiologic profile of cases of meningitis treated at a
      small hospital in Ribeirao Preto, State of Sao Paulo, and to compare it to those
      reported for other communities.METHODS: a retrospective study was conducted on
      103 patients admitted from January 1992 to July 1996 with clinical and laboratory
      diagnosis of bacterial meningitis. The clinical criteria for diagnosis were based
      on patient history and physical signs and symptoms, and the laboratory criteria
      were based on cerebrospinal fluid examination (aspect, cytology, biochemistry,
      Gram staining, culture and countercurrent immunoelectrophoresis) and blood
      culture.RESULTS: The etiologic agent was identified in 81.5% of cases:
      Haemophilus influenzae type b in 32%, Neisseria meningitides in 25.2%,
      Streptococcus pneumoniae in 8.7%, Staphylococcus aureus and epidermidis in 8.7%,
      and others agents in 6.9%. CONCLUSIONS: The study showed that the cases of
      bacterial meningitis treated at the Santa Lydia Hospital of Ribeirao Preto are
      caused by the same agents detected in other places, with Haemophilus influenzae
      type b being the predominant one. The study also suggests that when many people
      are involved in the collection of material for laboratory tests, recovery of the
      agent may become difficult.

PMID- 14685362
TI  - [Asthma - Clinical and epidemiological aspects of 237 outpatients in a
      specialized pediatric unit]
AB  - OBJECTIVE: The authors describe and evaluate epidemiological and clinical
      features of asthmatic outpatients attending a specialized pediatric unit.
      METHODS: Asthmatic patients of the Allergy and Immunology Unit of Department of
      Pediatrics (University of Sao Paulo) followed in the period from 1988 up to 1995
      were evaluated in a non-randomized and retrospective study. The patients were
      submitted to a protocol for associated diseases (gastroesophageal reflux,
      toxocariasis, tuberculosis, immunodeficiencies and other atopic diseases). Asthma
      severity was classified according to the 1st Brazilian Consensus for Asthma
      Management. RESULTS: 237 patients (128M:109F) were admitted with mean age of 86
      months. The first episode of wheezing occurred during the first year in 56% of
      them. Parental history of atopy was present in 61.6%. 53% of the patients had
      severe asthma in the first evaluation and it decreased for 35% at the time of
      this protocol. Cold weather (78.3%) and house dust (64.7%) were the commonest
      triggering factors. The following associated diseases were diagnosed:
      gastroesophageal reflux (n=57), toxocariasis (n=17), tuberculosis (n=7) and
      immunodeficiencies (n=16). 90.2% had other atopic conditions.CONCLUSION: The
      authors emphasize that the first asthmatic episode occurred earlier but there is
      a delay in sending the patients to specialized centers. The evaluation of
      clinical and epidemiological findings besides familial history are necessary for
      adequate treatment and early introduction of prophylactic measures.

PMID- 14685363
TI  - [Polysplenia syndrome associated to neonatal hepatitis]
AB  - OBJECTIVE: To report the unusual association between neonatal hepatitis and
      polysplenia syndrome.METHODS: Clinical, biochemical, histopathological, surgical
      and image analysis methods were used.RESULTS: The 36 days old patient presented
      hyperbilirubinemia with increase of direct reacting bilirubin and high alkaline
      phosphatase. The physical examination evidenced jaundice and hepatomegaly. The
      chest X-ray showed situs inversus and dextrocardia. Abdominal ultrasonography
      presented an increase in liver volume, mainly at the right lobe. There were two
      cystic lesions at the liver with absence of intrahepatic biliary tract
      dilatation. Absence of splenomegaly. Biliary scintigraphy didn't show any
      excretion of radioisotope to the duodenum while transoperative cholangiography
      presented contrast medium flowing to the duodenum lumen. During laparotomy it was
      possible to observe polysplenia, abdominal aorta to the right of the lower vena
      cava, gallbladder at the left lobe of the liver, appendix on the left side of the
      abdomen and sigmoid colon on the right side. The hepatic wedge biopsy was
      compatible with idiopathic neonatal hepatitis.CONCLUSION: The finding of
      polysplenia syndrome in patients with neonatal cholestasis doesn't necessarily
      indicate the recurrent presence of extrahepatic biliary atresia.

PMID- 14685364
TI  - [Brain abscess in childhren: A ten cases report]
AB  - OBJECTIVES: Considering that the brain abscess is rare in infants, with a high
      mortality rate, the objective of this paper is to report the clinical evolution
      of ten children with the diagnosis of brain abscess in the Pediatric Nursery of
      the Hospital das Clinicas of the Medical School of the Campinas State University
      (UNICAMP).METHODS: The data of the patients with diagnosis of brain abscess
      recorded between January 1986 and July 1995 were reviewed. The following data
      were analyzed: age, sex, clinical manifestations, physical examination,
      radiological data, etiological agent, treatment, complications and clinical
      evolution of the patients.RESULTS: The age of the patients varied from 2 to 13
      years (median 3 years); 6 of them were female. The neurological manifestations
      predominated, and 2 patients had history of prior otorhinolaryngological
      infection (chronic otitis media and sinusitis). Two patients had congenital
      cyanogenic cardiopathy (Fallot tetralogy and Pulmonary Stenosis with
      Interventricular Communication). The diagnosis and follow-up were made with
      computed tomography of the brain. In six cases there were one sole abscess
      located more frequently in the frontal lobe. The treatment in majority of the
      cases was broad-spectrum antibiotic association and surgical drainage. Five
      patients had neurological sequelae (seizure, hydrocephalus and paresis); one
      death occurred.CONCLUSIONS: Although rare, the brain abscess has to be remembered
      in patients that have neurological alterations associated to risk factors, as
      otorhinolaryngological infections and congenital cyanotic cardiopathy, being
      mandatory the realization of computed tomography of the brain to confirm the
      diagnosis.

PMID- 14685365
TI  - [Late hemorragic disease of the newborn: case report]
AB  - OBJECTIVE: In this study the authors review this subject, and call attention for
      the late hemorrhagic disease of the newborn, due to the severity and higher risk
      of mortality and neurological sequelae.METHODS: In this article, four cases of
      children, age raging from 12 to 21 days, with late hemorrhagic disease associated
      with vitamin K deficiency were reported. RESULTS: All newborns had multiple
      hemorrhagic manifestations of the disease. The systems more affected were
      digestive tract, urinary system, umbilical cord, respiratory system and nervous
      system.CONCLUSION: Three forms of hemorrhagic disease of newborn have been
      related with vitamin K deficiency. However, late vitamin K deficiency bleeding is
      not common and may not be diagnosed by pediatrician. This form of disease can be
      prevented by vitamin K prophylaxis administration after birth.

PMID- 14685366
TI  - [Retinopathy of prematurity: a disease demanding attention from the
      neonatologist].

PMID- 14685367
TI  - [Infant deaths: how to better investigate them (or how to prevent them)].

PMID- 14685368
TI  - [Investigation of infant and perinatal deaths: its use in planning public health
      policies].

PMID- 14685369
TI  - [Viral hepatitis: update].
AB  - OBJECTIVE: The authors present an update related to different types of viral
      hepatitis in infancy. The clinic-laboratorial and special outcome aspects are
      presented. METHODS: The most important articles about viral hepatitis were
      selected through Medline. The epidemiologic and clinical characteristics related
      to the subject are reported with emphasis on Brazilian data. RESULTS: This review
      analyzes the diseases caused by agents that have in common the viral origin and
      the hepatotropism, but the hepatitis are different particularly in those aspects
      related to outcome and prognosis. The B virus, for example, may be related to
      healthy asymptomatic carrier to acute hepatitis, chronic disease, cirrhosis and
      hepatocellular carcinoma. To date the known viruses are six: A, B, C, D, E and G.
      CONCLUSIONS: Viral hepatitis is a disease caused by one of the 6 different
      hepatotropic viruses which originate a wide range of clinical presentations. The
      viral distribution in Brazil is irregular; in some regions the B virus is
      prevalent, in others it is rare. The viral infections are the most important and
      the most frequent causes of liver disease in Brazilian children. The present
      review is to update viral hepatitis in infancy.

PMID- 14685370
TI  - [Prevalence of retinopathy of prematurity in very low birth weight infants].
AB  - OBJECTIVE: Evaluate the prevalence of retinopathy of prematurity (ROP) in very
      low birthweight infants (birthweight<1500 g). METHOD: A prospective examination
      was conducted on 102 neonates with very low birthweight admitted to the BAM-HC
      (FMUSP) between 01/01/92 and 12/31/93. The mapping of the retina with scleral
      depression was first conducted between 3rd and the 8th weeks of life, and it was
      repeated every 1 to 4 weeks until the vascularization of the retina was complete
      or the ROP was present. To classify the ROP the International Classification of
      ROP was used. For the purposes of statistical analysis, the most serious phase of
      ROP presented by the neonate was considered. RESULTS: In this study retinopathy
      of prematurity was present in 29.09% of the neonates, in 78.5% of those under
      1,000 g of birthweight, and 72.73% of those with less than 30 weeks of
      gestational age. Among the newborns with ROP, 77.05% were in phase 1, 13.11% in
      phase 2, and 9.84% in phase 3. Oxygen in mechanical ventilation and "CPAP" were
      statistically significant factors for the development the ROP. CONCLUSION: The
      ophthalmologic examination between the 3rd and 4th weeks of life was an important
      instrument for the detection of RP and should be done in all very low birth
      weight infants (weight<1,500 g), especially in neonates with less than 1,250 g
      and/or gestational age under 34 weeks.

PMID- 14685371
TI  - [Populational study of investigation of perinatal and infant deaths: methodology,
      validity of diagnosis and under-registration].
AB  - OBJECTIVE: The main objectives of the present study were to evaluate the
      percentage of under-registration of infant mortality in 1993 and compare it with
      the ones found 1982; to analyze the agreement between the official death
      certificates and the ones made by the referees. METHODS: The infant mortality of
      all children born in Pelotas, in 1993, was monitored through daily visits to
      hospitals, as it was done in 1982; monthly, cemeteries and public registration
      offices were visited to detect any deaths outside the hospitals. Besides the
      official death certificates, two independent referees established the underlying
      cause of death based on information from pediatricians, case-notes, autopsies and
      through a home visit to the parents of the children. RESULTS: The percentage of
      under-registration fell substantially from 24%, in 1982, to 5.4%, in 1993. The
      agreement between the official death certificates and the ones made by the
      referees showed satisfactory Kappas, unless for ill defined diseases such as
      sudden infant death, where the agreement was null. CONCLUSIONS: The authors
      conclude that there was a significant fell of the under-registration for infant
      death in Pelotas, and the ill defined causes such as sudden infant death have
      been hidden by the diagnosis of pneumonia.

PMID- 14685372
TI  - [Perinatal deaths in the city of Fortaleza: how many deaths could be prevented?].
AB  - OBJECTIVE: The main objective of this study was to explore the relationship
      between perinatal care and neonatal mortality as a component of the infant
      mortality. Indicators were selected to analyze some aspects of the quality of
      perinatal care attendance offered to pregnant women and their newborns. Specific
      attention was given to the avoidable perinatal deaths in the city of Fortaleza,
      Ceara. METHODS: Population-based, prospective study on incidence. The study was
      carried out collecting data of seventeen maternity units and two referral
      pediatric hospitals of the public health system in Fortaleza, the capital of the
      State of Ceara. All births, alive or dead, weighting 500 grams or more, along the
      whole year of 1995, were included in the study. The perinatal deaths' causes were
      studied according to the modified Wigglesworth classification (1989). RESULTS:
      Along the whole study period, 40,712 children were born and 1,337 perinatal
      deaths occurred. Among them 730 occurred during the fetal life and 607 during the
      first week of life. In spite of the low incidence of low-weight newborns (7.4%),
      the coefficients of fetal mortality were high (17.9 per thousand), as well as the
      perinatal mortality (32.8 per thousand) and neonatal mortality (15.1 per
      thousand). The number of avoidable perinatal deaths related to adequate perinatal
      care was estimated to be one third of the total deaths studied (458/1,323).
      CONCLUSIONS: The results indicate that the perinatal assistance in the city of
      Fortaleza is of low quality, with problems related to the health system
      organization and to the low quality of the care offered to women during
      pregnancy, at delivery and to the newborns in the delivery room as well as in
      neonatal wards.

PMID- 14685373
TI  - [Study of in vitro antimicrobial resistance of positive coprocultures to Shigella
      sp].
AB  - BACKGROUND: The gastroenteritis caused by Shigella sp (shigellosis) represents an
      important cause of morbimortality, especially in children under two years old. It
      is well known that the proper antimicrobial therapy can improve clinical state
      and diminish the disease dissemination. Increasing levels of resistance to drugs
      commonly used in the treatment of shigellosis have been described, and its
      sensibility has not been recently evaluated in our setting. OBJECTIVE: To
      evaluate the Shigella antimicrobial resistance in our setting. METHODS: A
      retrospective study was conducted using 106 coprocultures of patients,
      hospitalized or not, who have been assisted at HCPA and at HPV, during the period
      of 1994 to 1996, with the sensibility test done through the Kirby-Bauer technique
      of diffusion discs. RESULTS: Out of the 106 coprocultures studied, 35 (33%) came
      from HPV and 71 (67%), from HCPA. Considering the species, 58.8% were S.
      flexneri, 39.6%, S. sonnei, 0.9%, S. disenteriae and 0.9%, S. boydii. The
      resistance levels to usually indicated antibiotics were: ampicillin -57.5%,
      trimethropim-sulfamethoxazol -75.5%, and nalidixic acid -7.5%. CONCLUSIONS: These
      results show significant (p<0.001) in vitro antimicrobial resistance to
      ampicillin and trimethoprim-sulfamethoxazol and low resistance to nalidixic acid
      among Shigella sp. Thus, nalidixic acid may be an option to treat infections
      caused by resistant organisms.

PMID- 14685374
TI  - [Concentration of hemoglobin and hematocrit in schoolchildren, Campinas, Sao
      Paulo, Brazil].
AB  - OBJECTIVE: The purpose of this study was to describe the distribution of
      hemoglobin and hematocrit levels, and to correlate the hemoglobin levels with
      age, sex, income per capita, intestinal parasites, maternal and parenteral
      education. METHODS: One hundred and forty-six schoolchildren were studied. They
      were 48.5% female and 51.5% male. The children were 7.3 +/- 0.6 years old and
      presented 1.1 +/- 1.8 Brazilian minimum salary per capita. About 31% of them
      presented intestinal parasites. The schooling of their mothers was 5.2 +/- 3.0
      years and that of their fathers was 5.6 +/- 3.4 years. The cyanomethemoglobin
      method was used to determine hemoglobin concentration. Anemia was considered when
      the hemoglobin was below World Health Organization recommendations (<11 g/dl).
      RESULTS: The results showed no anemia among the schoolchildren. Most of them
      displayed hemoglobin concentration between 13 and 14 g/dl. Using the 25th
      percentile of the hemoglobin distribution (12.7 g/dl) to study the correlation
      between hemoglobin and the other variables, a positive association between
      hemoglobin and parenteral schooling (t=2.25, p=0.03) was detected. CONCLUSIONS:
      This correlation indicates the importance of education level for better life and
      health quality because education allows more information and understanding.

PMID- 14685375
TI  - [Prevalence of intestinal parasitosis in schoolchildren].
AB  - OBJECTIVE: Aiming to identify the prevalence and the social risk factors of the
      intestinal parasitosis in first grade school children of Campinas, State of Sao
      Paulo, Brazil. METHODS: Cross-sectional descriptive and analytical study based in
      personal and social data obtained by interview and feces analysis of 146 children
      to investigate Ancylostomatidae, Ascaris lumbricoides, Endolimax nana, Entamoeba
      coli, Entamoeba histolytica, Enterobius vermicularis, Giardia lamblia,
      Hymenolepis nana, Iodamoeba butschlii, Schistosoma mansoni, Strongyloides
      stercoralis, Taenia sp and Trichuris trichiura. RESULTS: The prevalence of
      Ascaris lumbricoides was 12.3% and of Giardia lamblia was 8.2%. The prevalence of
      intestinal parasitosis, in general, was 30.8%. The social risk factors for
      intestinal parasitosis were low maternal (OR=2.3) and paternal education
      (OR=3.9), small house (OR=3.0), large household (OR=2.7) and proletarian group
      (p=0.02). After adjusting for social variables, intestinal parasitosis was
      predicted by paternal education (p=0.003). CONCLUSIONS: The role of health
      education is important for disease prevention and the school is a natural place
      to reach the community living next to it.

PMID- 14685376
TI  - [Behavioral pain scales assessment in neonates].
AB  - OBJECTIVE: To establish the sensitivity and specificity of two behavioral pain
      scales in different gestational ages (GA). METHODS: 133 clinically stable
      neonates, <72 h of life, without diseases, analgesic/sedative use or Apgar<7 at
      5' were randomly assigned to receive capillary puncture--P or alcohol swab
      friction--F. Patients were divided according to GA (28-33 wk=A; 34-37 wk=B; 38-41
      wk=C ) and procedure: Group A-P (n=17, BW 1.5 +/- .4 kg); A-F (n=18, BW 1.5 +/-
      .4 kg); B-P (n=25, BW 2.5 +/- .5 kg); B-F (n=25, BW 2.4 +/- 0.6 kg); C-P (n=23,
      BW 3.3 kg +/- 0.5 kg); C-F (n=25; BW 3.3 +/- 0.4 kg). A neonatologist, blind to P
      or F, evaluated the Neonatal Facial Action Coding System (NFCS 0-8 pts, pain>3)
      and the Neonatal Infant Pain Scale (NIPS 0-7 pts, pain>3). All evaluations were
      performed prior to P or F, without (pr) and with foot heating (h), during (0), 1'
      and 3' after P or F. Reliability was assessed in 20% of the sample. Agreement
      rate was NFCS-97% and NIPS-95%. RESULTS: During the procedure, median NFCS and
      NIPS P score were greater than F (M. Whitney), p< or =0.0001) for A, B and C
      groups. At 1', NCFS and NIPS P scores were greater than F (MW, p< or =0.04) for A
      and C groups. For P patients, NFCS and NIPS scores were similar among the 3 GA
      groups at all study periods (K. Wallis). For F patients only at 0; NIPS scores
      were different (K. Wallis, p<0.03). During the procedure, NFCS>3 had sensitivity
      of 88-91% and specificity of 80-84%, NIPS>3 presented sensitivity of 77-87% and
      specificity of 68-83%. CONCLUSION: Both behavioral scales are sensitive tools for
      pain assessment in premature infants, although NFCS seems superior to NIPS.

PMID- 14685378
TI  - [Methotrexate in the treatment of the severe steroid dependent asthma].

PMID- 14685379
TI  - [Effects of maternal nutrition on the newborn infant].

PMID- 14685377
TI  - [Fragile X Syndrome: case report in two brothers].
AB  - OBJECTIVE: To alert the pediatricians about the phenotype of the patients with
      Fragile X Syndrome, because of it's high incidence and the variable degrees of
      incapacity that may occur. METHODS: Case report of two brothers with the
      classical findings of the Fragile X Syndrome (mental retardation, "Dumbo-like"
      ears, macroorchidism, among others), confirmed by cytogenetic studies. RESULTS:
      The diagnosis of the syndrome is based on the presence of a variable number of
      cells with fragile sites on the X chromosome at Xq 27.3. The DNA analysis
      revealed Fragile X locus in 14% of the brothers' metaphases and in 1% of the
      mother's. It was also observed that two cousins on the mother's side had the
      syndrome, confirmed by genetic studies. CONCLUSIONS: The recognition of this
      syndrome by the pediatrician is of extreme importance to an early
      multidisciplinary approach.

PMID- 14685380
TI  - [Parents' perceptions of their infants' hospitalization in a neonatal intensive
      care unit].
AB  - OBJECTIVE: To analyze the parents' perception of their infants hospitalization in
      a neonatal intensive care unit (NICU) and suggest a more humane and
      individualized care in this highly stressful environment. METHODS: We recorded
      and analyzed the interview of 20 young, low socioeconomic class couples having
      their first baby admitted to a NICU of a public hospital. RESULTS: Fear, stress
      and doubts were frequent feelings among parents. Heath professionals were often
      too busy to explain in detail what was happening. When talking to parents,
      doctors and nurses usually used medical terminology which was poorly understood
      by parents. CONCLUSION: The environment of a NICU is perceived by parents as
      being cold, impersonal and highly stressful. Listening to and understanding
      parents' needs is mandatory if one wants to provide a more humane and
      individualized care for high risk newborn infants and their families.

PMID- 14685381
TI  - [Methotrexate for steroid-dependent asthmatic children and adolescents].
AB  - INTRODUCTION: The administration of methotrexate as an antiinflammatory drug in
      asthma has been discussed and most of the studies were developed in adults. Its
      indication is restricted to steroid-dependent or steroid-resistant asthmatic
      patients. OBJECTIVE: This study evaluates the clinical and espirometric
      parameters of steroid-dependent asthmatic children, receiving methotrexate
      therapy. METHODS: Perennial steroid-dependent asthmatic patients (prednisone 30
      or 40 mg/dia), without associated disease, were evaluated by means of clinical
      and spirometric parameters. A maintenance dose of 10 to 17.5 mg/ week of
      methotrexate was administered. RESULTS: Six patients (3M;3F), aged 7 to 13 years
      old were included. There was improvement of clinical symptoms during the
      administration of methotrexate, in all patients, without significant change in
      the pulmonary function. During the use of methotrexate therapy three patients
      presented adverse reactions: leukopenia (1/3), vomiting (1/3) or Herpes zoster
      (1/3). The dose of prednisone was reduced in all patients, with total exclusion
      of prednisone in 3. Afterwards, there was a worsening of asthmatic symptoms in
      all patients, with reintroduction of corticosteroids. CONCLUSION: Methotrexate
      represents an alternative therapy for steroid-dependent asthmatics, and it may
      help to control symptoms of asthma and steroids use. Nevertheless, double-blind
      studies should be developed in children. Adverse effects must be considered
      before its indication, restricting its use to specialized centers.

PMID- 14685382
TI  - [Tissue and serum copper concentration in malnourished pregnant rats and in their
      offspring].
AB  - OBJECTIVE: To study copper status in malnourished pregnant rat and its offspring.
      METHODS: Female Wistar rats at age of 90 days and body weight of 200-/+20g were
      studied. These animals were randomly assigned to one of the 3 pregnant groups:
      control-PC, malnourished-MP1 (severe malnutrition) and MP2 (mild malnutrition),
      and their offspring, born by cesarean section, constituted the newborn groups:
      NBC, MNB1 and MNB2, respectively. The collected tissues (liver, muscle, bone,
      placenta and carcass) suffered previous liquid digestion, and the copper level,
      also in serum, was determined by atomic absorption spectrophotometry. RESULTS:
      The copper level in serum, bone, placenta and liver showed a significant
      difference between the pregnant groups; in the liver this difference was also
      significant between newborn groups. The values of the copper in the carcass were
      statistically lower in the newborn control animals. CONCLUSIONS: There is
      appropriate offer of maternal copper to the fetus which does not depend on the
      nutritional state of the mother, because there is a mobilization of the hepatic
      copper in the pregnant control group and also a mobilization of bone copper in
      the malnourished pregnant groups; however the intrauterine malnutrition is the
      one that determines inappropriate utilization of this ion by the fetus.

PMID- 14685383
TI  - [Prolonged rupture of the membranes and neonatal infection].
AB  - OBJECTIVE: To evaluate a schedule of assessment at birth of newborn from mothers
      with prolonged rupture of membranes (PROM >or= 24 hours), based on selected
      clinical and laboratorial parameters of infection. METHODS: Prospective study,
      including newborns admitted to the Nursery of the Hospital de Clinicas -
      University of Sao Paulo from May/1993 to December / 1994, whose mothers had PROM
      >/or 24 hours. In all newborns white blood cell count (umbilical cord and 24
      hours of life) and blood culture of umbilical cord were done. Antibiotics were
      given to newborns with clinical signs of chorioamnionitis, GA <or= 34 weeks
      and/or GA> 34 and < 37 weeks, plus at least one risk factor of infection. All
      newborns were classified into 4 subgroups: I (PROM <or= 48 hours), II (PROM > 48
      hours and < 7 days), III (PROM >or= 7 and < 14 days), IV (PROM >or= 14 days).
      RESULTS: The incidence of infection was 38.1% and was more frequent in newborns
      with GA < 34 weeks (p< 0.05). No statistical significance was noted among the
      subgroups analysed. Among the risk factors analysed, GA < 34 weeks was the main
      one. CONCLUSIONS: The authors recommend the use of prophylactic antibiotic
      therapy in newborns from mothers with PROM which have a GA <or= 34 weeks, aiming
      to decrease the risk of neonatal infection.

PMID- 14685384
TI  - [Nutritional supplementation in patients with cystic fibrosis].
AB  - OBJECTIVE: To evaluated the effect of short-term oral supplementation in the
      nutritional status of 14 patients with cystic fibrosis in 19 hospital admissions.
      METHODS: All patients received standard pulmonary therapy, and to 13 patients
      (Group I = GI) a high-fat oral supplement was offered besides the standard diet.
      The control group (GII) received the same diet except for the supplement.
      Anthropometric measurements, quantitative assessment of energy intake and serum
      biochemical parameters were determined on admission and prior to discharge from
      hospital. RESULTS: There was no difference in the weight gain between groups
      (median: GI=+1000 g; GII=+550 g), nor in the variations of height, skinfolds and
      body fat. Z scores were calculated (mean-/+SD: weight/age, GI=-2.19-/+1.0, GII=
      2.57-/+1.1; height/age, GI=-1.73-/+1.4, GII=-2.06-/+1.4 ), showing that those
      patients had chronic severe malnutrition, with no changes in Z Score in this
      period. The diet offered to the patients provided the RDA for calories only in
      the supplemented group, and this value was significantly higher compared to the
      non-supplemented group (mean -/+ SD : GI= 146-/+20% RDA; GII=105-/+13%RDA). The
      energy intake was significantly higher in group I (mean-/+SD: GI=126-/+22%RDA;
      GII= 81-/+27%RDA), and it increased significantly by the end of admission in this
      group. The biochemical assessment revealed low levels of prealbumin in both
      groups on admission (mean-/+SD: GI=11-/+10mg/dl; GII=8-/+8 mg/dl), with
      significant increase only in group I (mean-/+SD: GI=23-/+15 mg/dl; GII=8-/+11
      mg/dl). No variations in the levels of triglycerides were observed, but the
      cholesterol levels increased significantly in both groups. CONCLUSIONS: Although
      the weight gain was similar in both groups, prealbumin increased only in the
      supplemented group. This group had a higher energy intake than the non
      supplemented one, and it reached the RDA for calories.

PMID- 14685385
TI  - [Factors related to severe acute asthma in childhood - epidemiologic and clinical
      aspects].
AB  - OBJECTIVE: To study the epidemiologic and clinical factors related to severe
      acute asthma in patients hospitalized in pediatric intensive care unit (PICU).
      STUDY PROFILE: Prospective, epidemiologic. All admissions were observed. PATIENTS
      AND METHODS: All children with severe asthma admitted to PICU-HSL-PUCRS between
      January, 1994, and December, 1994. Their parents were asked to answer a
      questionnaire about clinical history and precipitating factors of bronchospasm.
      Clinical evolution was observed in each patient. RESULTS: 31 children were
      admitted on 42 occasions to the PICU for the treatment of severe asthma (7.3% of
      all admissions). The male: female ratio was 1.2:1.0 and the age mean was 25
      months. Respiratory viral infections were the main precipitating factor of asthma
      attacks (74%). Family history of asthma, atopy or tabagism were observed in 97%
      of the cases. A longer hospitalization period was associated with less than 1
      year age (p=0.0005), family history of tabagism (OR= 2.3) and occurrence of
      pneumonitis (p= 0.03). The long stay in PICU was associated with previous PICU
      admission (p=0.03), family history of tabagism (OR=2.0) and occurrence of
      pneumonitis (p=0.02). The main complication observed, especially in patients
      under 1 year receiving public health care, was pneumonitis, that was diagnosed in
      42% of these children. Patients assisted by a private doctor had a shorter
      hospitalization period and less pneumonitis complication. Mechanical ventilation
      was necessary in 10% of these patients. There was no death in our series.
      CONCLUSIONS: The incidence of severe acute asthma, associated with long staying
      in PICU and hospitalization, is related to low age (under 1 year), previous
      hospitalization due to bronchospasm, family history of asthma, atopy or tabagism,
      and ineffective medical care. These factors seem related to frequent crises
      causing more hospitalization indications. These children frequently present
      pneumonitis during their clinical evolution. Early and aggressive management in
      general benefit the clinical course of severe acute asthma. The mortality ratio
      for children with acute asthma who need PICU admissions is small.

PMID- 14685386
TI  - [Vitamin A and intrauterine growth retardation].
AB  - OBJECTIVES: Compare the levels of vitamin A in cord and maternal blood of 356
      mothers who had intrauterine growth retarded babies (IUGR) and 356 mothers who
      had adequate for gestational age (AGA) babies, identify a possible relationship
      between vitamin A and IUGR, and evaluate the correlation between maternal and
      blood levels of vitamin A. MATERIAL AND METHODS: Mothers were recruited from 4
      hospitals in Campinas, where an average of 1350 babies are born every month.
      Newborns were classified as being IUGR according to the Lubchenco classification.
      Gestational age of the newborns was evaluated by the Capurro method. Vitamin A
      was measured by high performance liquid chromatography (HPLC). RESULTS: More IUGR
      babies - 188/356 (33.1%) than AGA babies - 52/356 (14.6%) had low levels of
      vitamin A (<or= 0.70umol/l) in cord blood. However, the percentages of IUGR
      mothers (1.1%) with low levels of vitamin A were similar to AGA mothers (1.4%).
      CONCLUSION: The results suggest that vitamin A is the result of being born small
      rather than vice-versa. The explanations for the lower cord levels of vitamin A
      in IUGR babies compared to AGA babies are: inadequate supply of vitamin A by the
      mother to the foetus, poor foetal binding, increased utilization of vitamin A by
      the foetus, and poor storage by the foetus.

PMID- 14685387
TI  - [Prevalence of constipation in school children].
AB  - OBJECTIVE: To obtain the prevalence of constipation in school children, as
      chronic constipation is frequent among children attending our outpatient unit but
      only scarce data about community prevalence are available. METHODS: 1145 children
      of the two first school years (52.5% males, median age 8y 4mo) of 5 schools in
      underprivileged areas were evaluated. They answered a previously validated
      questionnaire, applied by specially trained students of a practical nurse school.
      Defecation of scybalous stools and/or straining / pain, usually, were used to
      characterize constipation, by a strict criterium. Soiling or fecal blood
      occurring as isolated symptoms were not included in the strict criterium, but
      were included in two other criteria. RESULTS: The prevalence of constipation was
      25.1% for boys and 32.9% for girls, by the strict criterium, and was more
      frequent among girls (p<0.05). Constipated boys and girls presented,
      respectively, 30.5% e 31.8% of soiling and 14.6% and 25.7% of fecal blood. In
      addition 61 boys and 49 girls presented either soiling or fecal blood as isolated
      symptoms and increased the prevalence by the other criteria. CONCLUSIONS: The
      prevalence of constipation in the observed community was high. Due to the
      severity of the possible complications, this could be considered a public health
      problem.

PMID- 14685388
TI  - [Hepatic mesenchimal hamartoma in neonates].
AB  - OBJECTIVES: To approach the diagnosis and management of two different features of
      hepatic mesenchymal hamartoma (HMH) in the neonate. METHODS: Report of two cases
      of HMH in newborns and review of the literature (MEDLINE and LILACS). RESULTS:
      Two cases of newborns with huge abdominal masses are presented, one of them
      complicated by rupture and hemorrhage during ultrasound manipulation, leading to
      hypovolemic shock. Urgent operation showed a ruptured giant hepatic cyst
      containing hemorrhagic yellowish fluid. The cyst was removed by edge resection at
      the level of hepatic segment 6 and the postoperative period was uneventful. The
      pathological analysis of the cyst including immunohistochemical tests revealed
      HMH. In case 2, with prenatal diagnosis of hepatic tumor, the mass progressively
      enlarged after birth, and a left hepatectomy was performed. The macroscopic
      appearance suggested hemangioma but the histopathological aspect indicated
      mesenchymal hamartoma with endothelial predominance. Nowadays both children are
      healthy and asymptomatic. CONCLUSIONS: The management of HMH is surgical
      treatment, because it does not disappear spontaneously. Some cases evolve to
      giant forms even in the neonatal period leading to fatal complications.
      Preoperative differential diagnosis from hemangioma is quite difficult for cystic
      types, and immunohistochemical analysis is important for pathological
      confirmation.

PMID- 14685389
TI  - [Necrotizing tracheobronchitis in an infant].
AB  - OBJECTIVE: To alert the pediatric emergency physician about an unusual cause of
      airways obstruction in children undergoing mechanical ventilation. METHODS: We
      report a case of necrotizing tracheobronchitis (NTB) in an 8-month-old boy and
      discuss the pathophysiology, diagnosis and treatment of this disease. RESULTS:
      This child presented a good outcome that was related to prompt diagnosis and
      treatment with bronchoscopic removal of necrotic tissue. CONCLUSIONS: The
      pediatric emergency physician must consider NTB in every children undergoing
      mechanical ventilation who presents acute episodes of airways obstruction,
      hypercarbia, lack of chest movement and pulmonary hyperinflation, even out of the
      perinatal period. This characteristic clinical presentation, when recognized, is
      an indication for emergency tracheobronchoscopy.

PMID- 14685390
TI  - [Biomedical journals: past, present, and future].

PMID- 14685391
TI  - [Epi Info and the assessment of nutritional status].

PMID- 14685392
TI  - [Congenital deafness].

PMID- 14685393
TI  - [Uniform requirements: why now and here].

PMID- 14685394
TI  - [Uniform requirements for manuscripts submitted to biomedical journals].

PMID- 14685395
TI  - [Infantile nutritional evaluation with the software EPI INFO (version 6.0),
      taking into consideration collective and individual approaches, degree and type
      of malnutrition].
AB  - OBJECTIVE: A systematization for an anthropometric infantile evaluation is
      proposed, employing the software Epi Info, version 6.0, considering the
      collective and individual approaches, as well as the degree and type of
      malnutrition. METHODS: The software Epi Info, sponsored by the World Health
      Organization, provides an infantile nutritional evaluation, which is based on
      three anthropometric indicators: weight-for-age, height-for-age and weight-for
      height. In order to quantify the observed data of each individual, three scales
      can be used. Among them, the Z score, which discriminates more efficiently the
      severe cases, is employed as a first choice. The reference pattern of the NCHS is
      used. Many cutoff points between eutrophy and malnutrition can be chosen, but the
      -2 Z score is the most employed. The child can be classified in three diagnostic
      categories: stunting, for height-for- age deficits; wasting, for weight-for
      height deficits; underweight, for weight-for-age deficits. Besides this, in a
      collective approach, the Epi Info software calculates the proportion of
      individuals in each populational group which have their anthropometric data
      deviated from the reference curve, constituting the percentage of observed
      abnormality (called standardized prevalence). RESULTS: In this paper, in which
      the analysis of a data file is presented as an example, the organization of the
      information provided by Epi Info is proposed, with the characteristics described
      below. In order to increase the diagnostic sensitivity, the collective approach
      is valued. Concerning the type of malnutrition, the English term "stunting" is
      substituted by "chronic malnutrition", "wasting" by "acute malnutrition" and
      "underweight" by "isolated weight deficit". Concerning the degree of
      malnutrition, the -2 and -3 Z scores are employed as cutoffs in order to define,
      respectively, a threshold between the moderate and severe forms. CONCLUSIONS: The
      proposed approach takes into account the identification of all forms of
      malnutrition, from the mildest to the most severe cases, takes into consideration
      both height and weight deficits and if the process is acute or chronic.
      Therefore, it is a tool for organizing data available with the use of the
      computer.

PMID- 14685396
TI  - [Childhood hypoglycemia - still a challenge].
AB  - OBJECTIVE: Hypoglycemia in the infant is potentially hazardous to the central
      nervous system(CNS), and any delay in solving the problem may impose irreversible
      sequelae. The aim of this review is to provide basic knowledge to the
      pediatrician to adequately deal with a hypoglycemic patient. METHODS:
      Bibliographic review was performed in the Medline for the last 10 years, and the
      most pertinent papers were selected. RESULTS: Even today, there are discrepancies
      as for the best conduct in the hyperinsulinemic patients. The surgical or
      clinical approaches have had the support of very important authors. Some state
      that the best choice is the total pancreatectomy, in which 95% of the pancreas is
      removed, with all its long-term sequelae, while others emphasize the preservation
      of the pancreas with drug therapy instead of pancreatectomy. CONCLUSIONS: The
      doctor who takes care of a hypoglycemic child has to remember that the biggest
      task is to preserve the CNS integrity, and all the efforts must be made to
      provide an adequate glucose supply to the brain, otherwise irreversible
      consequences will ensue.

PMID- 14685397
TI  - [Causes of pre-verbal deafness in an institutionalized population, emphasizing
      genetic etiology].
AB  - OBJECTIVE: To investigate the causes of pre-verbal deafness in an
      institutionalized population emphasizing genetic etiology, considering the
      scarceness of national data in this field. METHODS: Based on the promptuaries of
      658 pupils from 18 institutions for deaf people in Recife, information about
      audiological tests, laboratory examinations, etiology, associated anomalies,
      consanguinity and other deaf persons in the family was obtained; dysmorphologic
      examination was performed in 557 pupils; all the families with recurrent cases of
      deafness were investigated, having the pertinent pedigrees been constituted.
      RESULTS: About 13% of the studied population probably manifest genetic deafness;
      the autosomal recessive, autosomal dominant and X-linked recessive patterns of
      inheritance were observed, respectively, in 87.7%, 8.8% and 3.5% of the familial
      cases; among the examined pupils, 4.3% presented specific dysmorphic syndromes or
      anomalies associated with deafness; the acquired causes and unknown etiology were
      represented by 41.5% and 45.5% respectively. CONCLUSIONS: Obtained frequencies
      for the distinct causal factors of pre-verbal deafness are within the spectrum of
      variation of the frequencies observed in similar works, pointing out that in a
      great number of cases the etiology is unknown.

PMID- 14685398
TI  - [Morbidity and malnutrition risk factors in children followed up by a child
      health care program].
AB  - OBJECTIVE: The objective of this study was to identify risk factors associated
      with malnutrition and morbidity in the population of children accompanied by the
      Child Health Care Program in Embu, Sao Paulo (Brazil), with the aim of giving a
      better direction to health activities. METHODS: The case-study was constituted by
      a cross-section of 1,024 children, corresponding to 25.0% (probabilistic
      sistematic sample) of the total of children under 12 months registered in six
      primary health care centers in the Municipality, during the period from July 1988
      to July 1989. The risk factors were analyzed according to the presence or absence
      of hospitalization and weight evolution - favorable or unfavorable - until two
      years of age. For the statistical analysis the multivaried approach was used,
      through the tecnique of logistic regression. RESULTS: Of a total of 1,024
      children, 428 (39.1%) were classified as high risk, 658 (60.1%) as low risk and 8
      (0.8%) presented pathologies at their first appointment, being excluded from the
      analysis. Prematurity (adjusted RR = 3.35), serious illness in the newborn
      (adjusted RR = 4.12) and the death of a younger brother or sister of less than
      five years (adjusted RR = 2.70) constituted risk factors for hospitalization in
      the first two years of life. Weight at birth between 2,500 and 2,750 g (adjusted
      RR = 2.46), brother or sister with malnutrition (adjusted RR = 4.17) and maternal
      age of 18 years old or less (adjusted RR = 1.87) constituted risk factors for
      unfavourable weight evolution. CONCLUSIONS: These results, as well as the process
      of carrying out this study, supported the reformulation of the Child Health Care
      Program in Embu, permitting differentiated action for the highest risk group,
      thus garanteeing the essential for all.

PMID- 14685399
TI  - [Fetal hydronephrosis: postnatal management and follow up].
AB  - OBJECTIVE: Fetal hydronephrosis is being detected with increasing frequency and
      probably this observation will increase as the quality of ultrasound equipment
      improves. This study evaluated etiology and postnatal clinical outcomes of
      prenatally detected hydronephrosis. METHODS: In a period of 13 years 148 infants
      were referred with fetal hydronephrosis. The initial evaluation, after
      prophylaxis, included ultrasound and voiding cystography. Sequential evaluation
      was determined by initial findings. RESULTS: Postnatal predominant diagnosis were
      pelviureteric junction obstruction (24%) and hydronephrosis without obstruction
      (18%). Follow up median was 38.7 months. Renal function deteriorated in 13 (8.8%)
      children and 11 (7.4%) died during follow up. Bad prognosis was associated with
      urethral obstruction. CONCLUSIONS: Fetal hydronephrosis is a clue of urinary
      tract anomalies. Urinary tract infections and delay in postnatal diagnosis must
      be prevented in children with this uropathy.

PMID- 14685400
TI  - [Bone mineral density: correlation with body weight, height, bone age and insulin
      like growth factor].
AB  - OBJECTIVE: To evaluate bone mineral density and bone mineral content of skeleton
      and lumbar spine of pre-pubertal children and to correlate results thus found
      with sex, bone age, body weight, height and insulin-like growth factor 1 serum
      level. METHODS: 26 boys and 12 girls aged between 7 and 8 years old, students
      from a Sao Paulo public school, were studied. They all presented weight and
      height between 2.5 and 97.5 percentiles of the Brazilian childrens curve, lack of
      secondary sex characteristics, no reports on chronic diseases and normal physical
      examination. Bone age was determined from radiograms of the left hand and wrist.
      Serum levels of insulin-like growth factor 1 were measured by radioimmunoassay.
      Bone mineral density and bone mineral content were measured in skeleton and
      lumbar spine using a dual X-ray absorptiometry equipment. RESULTS: The mean
      values of skeleton bone mineral density found were 0.812 -/+ 0.057 g/cm(2) in the
      girls and 0.839 -/+0.053 g/cm(2) in the boys, while the respective mean lumbar
      values were 0.649 -/+ 0.092 g/cm(2) and 0.657 -/+ 0.062 g/cm(2). The mean values
      of skeleton bone mineral content found were 840 -/+ 181g in the girls and 919 -/+
      133 g in the boys, while the respective lumbar values were 13.3 -/+ 3,0g and 14.5
      -/+ 2,4. It was found that the bone mass of children at this age corresponds to
      about 50% of the bone mass pick found in the young adult. No significant bone
      mass differences between sexes were found. No correlation was found between bone
      mass and insulin-like growth factor 1 serum levels. Positive correlations between
      bone mass and body weight and bone age were found. CONCLUSIONS: In pre-pubertal
      children (1) the analysis of bone mass should be interpreted mainly as a function
      of body weight and (2) bone mineral density of the lumbar spine and skeleton
      correlate with bone age and may represent an additional parameter of skeleton
      maturation.

PMID- 14685401
TI  - [Cutaneous vesicostomy in children].
AB  - OBJECTIVE: In this report we assessed the results obtained with cutaneous
      vesicostomy for the temporary diversion of urine in small children. PATIENTS AND
      METHODS: We analyzed the medical records of 20 patients (17 boys and 3 girls)
      that underwent this type of diversion at our institution. Cutaneous vesicostomy
      was done due to severe hydronephrosis with low renal function and/or urinary
      tract infection with metabolic acidosis. RESULTS: The urinary tract anomalies
      were posterior urethral valves in 12 children, vesicoureteral reflux in 7 and
      anterior urethral valve in one. Elevated levels of serum urea and creatinine were
      found in 16 patients during pre-operative evaluation. During the follow-up there
      was a reduction of hydronephrosis in all patients, and 5 progressed to chronic
      renal failure. These patients had worse development of weight and body lenght
      when compared to those with normal renal function. The post-operative
      complications were prolapse in 2 patients and stenosis of the stoma in 2.
      CONCLUSION: cutaneous vesicostomy has proved to be an useful form of urinary
      diversion. In our experience it is an effective and easily reversible temporary
      treatment for infants and children with severe hydronephrosis associated with
      urinary tract infection due to infravesical obstruction or vesicoureteral reflux.

PMID- 14685403
TI  - [Fungal endocarditis in the neonatal period. Report of a case with large right
      atrial mass].
AB  - OBJECTIVE: To draw pediatricians' attention to diagnoses of Fungal Endocarditis,
      which may ensue as a result of intravascular catheter use. METHODS: The authors
      report a case of Fungal Endocarditis during the neonatal period, which was later
      confirmed through a histopathological exam. They also review literature of the
      theme - from 1980 on - in MEDLINE and LILACS. RESULTS: A newborn was admitted to
      the hospital with kernicterus - but no previous cardiopathy - and required the
      use of an intravascular catheter. During the evolution, the baby developed a
      recurring fever and systolic murmur. Submitted to exam, the tip of the catheter
      showed the presence of Candida sp. An ecocardiographic exam showed a great right
      intra-atrial mass, which was surgically removed. The histopathological exam
      confirmed the diagnosis of fungal endocarditis. CONCLUSION: Fungal Endocarditis
      should be thought of as a possible diagnosis when great intra-atrial masses are
      found in neonates with a history of intravascular catheter use and a non-specific
      infectious condition.

PMID- 14685402
TI  - [Lateral sinus thrombophlebitis and cervical abscess as a complication of chronic
      otitis media].
AB  - OBJECTIVE: To focus on two rare complications of cholesteatomatous chronic otitis
      media. METHODS: A case of two simultaneous complications of cholesteatoma
      (lateral sinus thrombophlebitis and Bezold's cervical abscess) in a 7 year-old
      boy is reported. Thereafter, a review of the international literature about both
      complications is carried out. RESULTS: A 7 year-old white male patient was
      referred for assessment with high fever, obnubilation, cervical mass and
      otorrhea, being non-responsive to the clinic treatment, with the diagnostic
      hypothesis of infectious parotitis. The clinical examination and radiologic study
      demonstrated lateral sinus thrombophlebitis and cervical abscess due to
      cholesteatoma in the right ear. After being submitted to surgery and prolonged
      intravenous antibiotic therapy, the patient presented a favorable outcome, with
      little morbidity. CONCLUSION: Despite the incidence of complications of otitis
      had decreased in the last decades, they are still a challenge for the clinician,
      especially because of the insidious manner of presentation, usually hidden with
      the indiscriminate use of antibiotics.

PMID- 14685405
TI  - [Risk factors for asthma].

PMID- 14685404
TI  - [Giant hemangioma treated with interferon alpha-2a].
AB  - OBJECTIVE: The authors describe a case of giant hemangioma treated with
      interferon alpha-2a and review the role of this drug and other therapeutic
      modalities in the management of vascular lesions. METHODS: A seven month-old
      child with giant hemangioma and persistent bleeding, anemia and repeated
      infections was treated with interferon alpha-2a. The drug was administered at the
      dosage of 3 million units/m(2)/day, subcutaneously, for nine months. RESULTS:
      Response to treatment was considered excellent, with regression of 90% of the
      lesion, control of bleeding, infection and anemia, and catch-up growth. No
      untoward effects were observed. CONCLUSION: Interferon alpha-2a should be
      considered as a valid therapeutic option in selected cases of hemangioma in
      children.

PMID- 14685406
TI  - [Coagulase-negative Staphylococcus in blood cultures: infection or
      contamination?].

PMID- 14685407
TI  - [Pollution and airway diseases].

PMID- 14685408
TI  - [Pulmonary function tests in children and adolescents].
AB  - OBJECTIVE: Evaluation of pulmonary function in pediatric patients. METHODS:
      Bibliographic review of the main techniques of pulmonary function testing.
      CONCLUSIONS: Pulmonary function tests are an important complement to the
      diagnosis of respiratory illnesses in children. They can also be of help in the
      follow-up and treatment of these illnesses, and since they can reproduce
      physiopathological phenomena under laboratory conditions they can also be of help
      in the study of several diseases. The basic spirometric tests most often used are
      the volume-time curve (V-T curve) and the flow-volume curve (F-V curve).
      Bronchial hyperreactivity can be assessed through provocation and effort tests.

PMID- 14685409
TI  - [Risk factors and clinical evolution of asthma in children].
AB  - OBJECTIVE: The purpose of this study was to obtain data on the clinical evolution
      and risk factors related to asthma in children followed as outpatients in our
      Division of Allergy. METHODS: The asthmatic group consisted of 165 children (107
      boys, 58 girls), between the ages of 3 and 14 years. All children were atopic and
      had a positive skin prick test to D. pteronyssinus. The control group consisted
      of 40 healthy children (20 boys, 20 girls), within the same age range, without
      personal history of asthma or other atopic disease and with negative skin prick
      test to D. pteronyssinus. The mothers were interviewed to obtain data on: a)
      clinical evolution, b) family history of asthma or any other atopic disease, c)
      description of the house environment. RESULTS: 1) in approximately half of the
      cases symptoms started on the first year of life. Mothers were not informed of
      the condition at the time; 2) upper respiratory tract infections and
      bronchiolitis were responsible for triggering the first wheezing episode in most
      cases and remain the main precipitating factors in the first year of the disease
      whilst allergens, irritants, sinusitis, physical exertion and emotional factors
      were the main precipitating factors between the ages of 5 and 13; 3) changes in
      climatic conditions precipitated acute attacks throughout the evolution of the
      disease and; 4) asthma was not the only allergic manifestation, allergic rhinitis
      being the most frequent associated condition; 5) family history of atopy
      (Relative Risk (RR) = 2.40; 95% confidence interval (CI95%) = 1.60-3.50);
      maternal history of asthma (RR = 2.23; CI95% = 1.10-4.63) and the presence of
      smokers in the house (RR = 2.30; CI95% = 1.20-4.31) were the main risk factors
      for the manifestation of asthma. CONCLUSIONS: a) there were no differences
      between boys and girls regarding the evolutionary aspects, b) asthma was
      underdiagnosed, c) family history of atopy, maternal history of asthma, and the
      presence of smokers in the house were risk factors for the manifestation of
      asthma.

PMID- 14685410
TI  - [Coagulase-negative Staphylococcus sp. in blood cultures from infants less than
      60 days old: infection versus contamination].
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of infection
      versus the prevalence of contamination in infants less than 60 days old who had
      blood cultures positive for CoNS. MATERIAL AND METHODS: Between February and June
      - 1993, a number of 45 blood cultures positive for CoNS from 41 patients were
      studied. Patients were classified in three groups according to their clinical and
      laboratorial data: I- infected patients, II- non-infected patients and III-
      dubious. RESULTS: The results showed that 11 patients (26.8%) were included in
      group I, 25 (61%) in group II (contaminated blood cultures), and 5 (12.2%) in
      group III. CONCLUSION: It is suggested that more than one blood culture should be
      requested before treatment with antimicrobials, avoiding unnecessary
      administration of antibiotics.

PMID- 14685411
TI  - [Lower airways and pollution].
AB  - OBJECTIVE: The purpose of this study is to demonstrate the prevalence of lower
      respiratory airway diseases in children exposed to different sources of
      environmental pollutants. METHODS: An epidemiological survey (using a
      questionnaire) was conducted in Sao Paulo State with three groups of children
      (1000 in each group): in the city of Sao Paulo, urban pollution; in Piracicaba,
      sugar cane burning area; and in Tupa and Batatais, pollution-free rural zone.
      RESULTS: As for asthma/bronchitis and/or pneumonia, children from Piracicaba and
      Sao Paulo presented rates of 14 and 11% respectively, compared with 10% in Tupa
      and Batatais. Absenteeism from school was 17% in Piracicaba, 11% in Sao Paulo and
      9% in Tupa and Batatais. Hospitalizations due to respiratory complications
      (asthma/ bronchitis or pneumonia) was 4% in Sao Paulo, 3% in Piracicaba and 2% in
      Tupa and Batatais. All the above results had statistical significance (p < 5).
      CONCLUSIONS: High prevalence of lower respiratory airways infections and their
      complications in children exposed to different sources of environmental air
      pollutants demonstrate the need for a more efficacious control environment
      pollution.

PMID- 14685412
TI  - [The influence of intrapartum antibiotic therapy on the diagnosis of early-onset
      neonatal sepsis].
AB  - OBJECTIVE: To determine the influence of intrapartum antibiotic therapy on blood
      and secretion cultures of newborn infants suspected of early-onset sepsis.
      MATERIAL AND METHODS: From August 1995 through July 1996, 69 sequential newborn
      infants with early-onset sepsis or septic syndrome were included in the study.
      All of them were followed for the end point: positivity of blood, urine, CSF,
      tracheal secretion or umbilical catheter cultures. The sample size was figured
      out to be 17 for each group, for a significant level of 5%. RESULTS: Seventeen
      mothers were treated with antibiotic. Ampicillin alone or in association with
      other drugs was utilized in 70% of them. Urinary tract infection occurred in 9
      mothers (53%), ammonites in 6, one mother had both and another one had
      erysipelas. Thirteen newborn infants had positive cultures in the group whose the
      mothers had not received antibiotic (n=52), none of the 17 newborn infants
      delivered by the mothers treated with antibiotic had any positive culture
      (p=0.0164). The relative risk of positive culture in a septic neonate if the
      mother is not treated with antibiotic is 12 times higher than if the mother is
      treated with antibiotic. CONCLUSION: The use of intrapartum antibiotic in newborn
      infants with early-onset sepsis or septic syndrome may cause a negativity of
      cultural exams, increasing the difficulty of the diagnosis of early-onset
      neonatal sepsis.

PMID- 14685413
TI  - [Congenital hypothyroidism screening program: preliminary results].
AB  - OBJECTIVE: The authors report early results of a screening program for Congenital
      Hypothyroidism in Santa Catarina, Brazil. METHODS: All the assays (82.709)
      analysed by Laboratorio Central (LACEN) between July 1993 and December 1994 were
      studied. A blood sample was collected on filter paper for serum Thyroid
      Stimulating Hormone (TSH) measurement by fluoroimmunoassay, in triplicate. All
      children who had persistent abnormal TSH values (cord blood: TSH > 30 micro U/ml;
      from 2 to 7 days: >20 micro U/ml; older than 7 days: > 10 micro U/ml) were
      recalled for clinical evaluation. RESULTS: Out of 82.709 infants aged from 0 to
      60 days (40% of the deliveries in this period), 304 presented abnormal results of
      TSH and 34 were confirmed as Congenital Hypothyroidism. The mean age of beginning
      the treatment was 45 days of life. CONCLUSIONS: The prevalence (1:2500) was
      higher than that observed in other countries, probably because some children had
      Transient Congenital Hypothyroidism. Nevertheless, sex prevalence was similar to
      that described in the literature. Clinical manifestations were inespecific which
      reinforces the importance of this kind of screening. Efforts have been done to
      improve the program in order to begin earlier treatment.

PMID- 14685414
TI  - [Recurrent abdominal pain at the Pediatric Gastroenterology Outpatient Clinic].
AB  - OBJECTIVE: To analyze the features of pediatric patients with recurrent abdominal
      pain, identify the main ethiologic diagnoses and their clinical and laboratorial
      differences. PATIENTS AND METHODS: We studied the medical records from 167
      children attended at a pediatric gastroenterology outpatient clinic. After
      analysis of the entire sample, the patients were divided in groups according to
      their diagnosis. Those patients with more than one diagnosis were arranged into a
      subgroup named multiple diagnosis. Statistical analysis was performed with
      Kruskall-Wallis test for numeric variables and chi-square test for non-numeric
      variables. RESULTS: The patients age ranged from 3 to 17 years (median 9), the
      number of consultations ranged from 1 to 16 (median 2) and the period of
      attendance ranged from 1 to 37 months (median 4). The pain was mainly
      periumbilical (35.8%) and crampy-like (76.1%). The main diagnoses found were
      chronic intestinal constipation (58.6%), intestinal parasitosis (22.8%), and
      peptic disease (20.4%). In 34 patients (20.3%) we were not able to establish the
      diagnosis. Among the groups, there was statistically significant difference in
      age (p=0.00003), number of consultations (p=0.00004), period of attendance
      (p=0.00001), kind of pain (p=0.0003), intestinal habit (p=0.0002), stool features
      (p=0.0001), and evolution (p=0.0006). CONCLUSIONS: The authors conclude that
      finding organic disease in patients with recurrent abdominal pain is much more
      common than it was expected. The pediatrician always has to consider the
      possibility of multifactorial origin for these patients' complaints.

PMID- 14685415
TI  - [Prevalence of iron deficiency anemia and risk indicators in children from 12 to
      18 months attended at the outpatient clinic of Instituto de Puericultura e
      Pediatria Martagao Gesteira].
AB  - OBJECTIVES: The prevalence of iron deficiency anemia and the associated risk
      indicators were studied in children from 12 to 18 months at the outpatient unit
      of IPPMG, in order to evaluate and monitor the service. METHODS: This is a cross
      sectional descriptive study of 288 children seen at the outpatient unit of IPPMG,
      from January to December 1993. Anemia was diagnosed by dosage of seric
      hemoglobin. The studied risk indicators were: prenatal care, birth weight,
      pediatric follow-up, socio-economic aspects, breast-feeding pattern, nutritional
      status, and iron prescription. Data were computerized and analyzed by EPIINFO and
      EGRET softwares. Statistical analysis was performed by Pearson chi(2), and breast
      feeding pattern was analyzed by the Kaplan-Meier survival curves. RESULTS: Fifty
      percent of all children had anemia and 13.2% had severe anemia. Children had an
      early entry to follow-up at the clinic, and the number of consultations was
      adequate, according to the recommendations of the Ministry of Health. Only 27% of
      families had a "per capita" income above one minimum salary, although most had
      adequate housing and environmental conditions. The median duration of breast
      feeding was 7.8 and of exclusive breast-feeding was 3.2 months. No association
      between anemia and income, early weaning, low-birth weight or undernutrition was
      found. CONCLUSION: The prevalence of anemia was extremely high, indicating the
      need for a specific monitoring system for the occurrence of iron deficiency
      anemia in this service.

PMID- 14685416
TI  - [Pilocytic astrocytoma in childhood: presentation of six cases].
AB  - OBJECTIVE: To present 6 cases of pilocytic astrocytomas whose clinic,
      epidemiological and histopathological aspects were studied. METHODS: Between 1990
      and 1994 the records of the laboratories of pathology of the main hospitals in
      Curitiba were analysed and all cases of pilocytic astrocytomas were studied with
      special attention to age of onset, sex and site of the lesions. The biopsies,
      which were reviewed, have been processed according to conventional techniques and
      in a few cases electron microscopy and immunohistochemistry was further done.
      RESULTS: Five patients were females and 1 was male. Medium age was 4,5 years
      (range 1-8). The pilocytic astrocytomas affected optic chiasm (n=3), midline of
      cerebral hemisfere (n=2) and third ventricle (n=1). The symptoms reflected the
      location and extension of the tumour. The commonest signs and symptoms were those
      of intracranial hypertension, visual disturbances, hydrocephalus, among others.
      The patients were treated with surgical ressection and chemotherapy. Three
      patients died after a medium survival of 45 days, and three remain alive.
      CONCLUSIONS: The authors emphasize that pilocytic astrocytoma, mainly the
      juvenile variant, affect mostly the midline brain structures of infants through
      signs of visual disturbance. These lesions are low grade astrocytomas and should
      be treated predominantly by total surgical ressection.

PMID- 14685418
TI  - [HIV / AIDS - is it necessary or possible to reduce mother to infant
      transmission?].

PMID- 14685417
TI  - [Liver transplantation: the dilemma of the lack of organs and the choice of the
      ideal receiver].

PMID- 14685419
TI  - [To what extent do parents have the right to decide for their children?].
AB  - OBJECTIVE: To review the hierarchy of bioethical principles when there are
      conflicting interests between the medical team and the child's parents in
      decision making in pediatrics. Our hypothesis is that when the parents decisions
      can be questioned, they loose the right to decide for their children. METHODS:
      The case of a 9-year-old girl from a Jehova's Witness family is presented. She
      was a candidate for renal transplantation but her parents were against blood
      transfusion in case it was required. A member of the medical team presented a
      denounce to the hospital Medical Ethic Committee and asked for advice. Several
      materials were reviewed for the ethic aspects involved: the Bioethic Live Plus
      1973-4/96, literature provided by people from Jehova's Witnesses, the chapters
      about ethics in the main pediatric text-books, a journal on Bioethics published
      by the Brazilian Federal Medical Board, and the Child and Adolescent Act
      (Brazilian Law 8,069 from January 13th, 1990). RESULTS: The Committee's finding,
      based on ethic and legal aspects reviewed in the literature about similar cases,
      favors the beneficence principle under the justification of preserving life as an
      ultimate goal, and recommends the interference of the Children and Youth Court so
      that the patient's interest and greater benefits prevail. Nevertheless, it also
      recommends that the medical team should make every possible effort to avoid blood
      transfusion in order to respect this conception of life and protect the people
      who believe in it, in accordance with the fundamental principle of bioethics
      which postulates the respect for human dignity and autonomy of belief.

PMID- 14685420
TI  - [Follow-up of pediatric patients evaluated for liver transplantation].
AB  - OBJECTIVE: To analyze the evolution of pediatric patients chosen for hepatic
      transplantation. METHODS: A review was made of the clinical charts of the first
      65 children and adolescents with chronic liver disease, aged 5 months to 19 years
      (X = 6.8%), chosen for liver transplantation during the period of August 1994 to
      March 1996. Data refer to the patients' demographic characteristics, etiology of
      their liver disease, their psychosocial situation and of their parents, and their
      clinical and laboratorial evaluation. According to the severity of the disease,
      patients were classified as active (waiting for a donor), in evaluation, inactive
      (compensated liver disease), and excluded for psychosocial or medical conditions,
      or because of bad indication. RESULTS: Eight patients (12%) received
      transplantation, and one of them died. Seven (11%) died when in evaluation or
      waiting for a donor. Ten patients (15%) were excluded from the waiting list: 6
      for social problems, and 4 for medical problems. No patient was excluded for bad
      indication. Six patients are in the active list, waiting for donor. The other 23
      patients (35%) are in evaluation, and 11 (17%) are classified as inactive in the
      waiting list. CONCLUSIONS: Eleven patients (17%) were not operated on due to the
      advanced stage of the liver disease. We emphasize the necessity of organ
      donation, and the early contact of the patients with a reference center.

PMID- 14685421
TI  - [Study of 176 HIV-seropositive children in Santa Catarina State].
AB  - OBJECTIVE: The incidence of the acquired immunodeficiency syndrome (AIDS) has
      increased in Santa Catarina State in Brazil over the last years, with a high
      number of infected women and children. The purpose of this study was to establish
      the main characteristics of the children from this State whose HIV serologic
      tests were positive. METHODS: This was a descriptive study of 176 children with
      positive serologic tests to HIV, conducted in the Hospital Infantil Joana de
      Gusmao, Florianopolis City, Santa Catarina State, Brazil. RESULTS: Most of the
      children (105 cases, 59.6%) were born in Florianopolis, Capital of Santa Catarina
      State, and Itajai (22 cases, 12.5%). Vertical transmission of HIV was observed in
      167 patients (94.9%). Among 167 HIV-positive mothers, 77 (46.1%) of them acquired
      the virus by sexual transmission and 35 (21.0%) by use of injectable drugs.
      However, among 89 HIV-positive fathers, 63 (70.7%) of them used to take drugs.
      The average age of the HIV-positive children whose serologic tests became
      negative was 10.5 months. Among 103 symptomatic patients, 87 (84.5%) presented
      hepatomegaly, 81 (78.6%) lymphadenopathy, 66 (64.0%) splenomegaly, 59 (57.3%)
      skin bruises, 54 (52.4%) recurrent bronchopneumonia and 50 cases (48.5%)
      recurrent diarrhea. The most frequent opportunistic infection was mucocutaneous
      candidiasis that occurred in 41 children (39.8%). CONCLUSIONS: The
      characteristics were similar to those reported in the literature. A great
      concentration of HIV infected persons was observed in the coast area where there
      are three harbor towns, an elevated number of injectable drug users and presence
      of many tourists.

PMID- 14685422
TI  - [Evaluation of the complement system and immunoglobulin G levels in cord blood.
      Relationship with gestational age and intrauterine growth].
AB  - OBJECTIVE: To evaluate the complement system in cord blood and its relationship
      with the degree of maturation and intrauterine growth. METHODS: Serum levels of
      C(3), C(4) and CH(50) were measured in premature, small for gestational age and
      appropriate for gestational age newborns. The activation of complement system was
      searched by clivage product determination C(3d) and C(4d). Serum IgG levels were
      also determined in all children. RESULTS: The levels of C(3), C(4), CH(50) and
      IgG were significantly lower in preterm (p < 0,001); C(4) and IgG values were
      also significantly lower in small for date than those in normal newborn. C(3d)
      and C(4d) were not detected, indicating that the complement system had not been
      activated. CONCLUSIONS: The lower complement component levels and IgG in newborn
      are related to gestational age as well as to intrauterine growth.

PMID- 14685423
TI  - [Epidemiological pattern of lymphatic filariasis in children living in endemic
      areas].
AB  - OBJECTIVE: Lymphatic filariasis still represents a major public health problem in
      the city of Recife. In spite of the fact that previous surveys had already shown
      high frequency of microfilaraemia in pediatric population, the prevalence of
      filarial disease and the microfilaraemic pattern of this group were unknown. This
      paper describes the clinical-epidemiological pattern of filariasis in children
      and adolescents living in two highly endemic areas of Recife. METHODS: The
      parasitological survey was done through a census carried out between December
      1990 and July 1991. Thick drop technique (45 micro l) was performed on a total of
      1,464 children and adolescents between the ages of 5 and 14, of whom 967 were
      submitted to clinical examination. Positive cases had their blood recollected (60
      micro l) to measure the microfilaraemic density. RESULTS: The microfilaraemia
      prevalence was 6.4 %. In the age groups of 5 to 9 and 10 to 14 a microfilaraemia
      prevalence of respectively 4.6% and 8.3% was observed. The microfilaraemic
      density varied from 3 to 864 microfilariae per 60 microl of blood, there having
      been no statistically significant difference between the sexes and age groups
      (p<0.05). 6 cases (0.6 %) of acute filarial disease and 11 of chronic filarial
      disease (1.1%) were identified, hydrocele being the principal manifestation
      found. Lymphadenopathy was found in 22% of the children, statistical association
      with microfilaraemia being observed (p<0.001). CONCLUSIONS: The results of the
      parasitological survey show the strong presence of children in the contingent of
      microfilaraemic individuals, indicating an early and intense exposure to
      filariasis in the population studied.

PMID- 14685424
TI  - [Identification of the groups most vulnerable to infant malnutrition through the
      measuring of poverty level].
AB  - OBJECTIVE: To test an instrument measuring the socioeconomic level, specially
      designed for low income urban populations, to be used in the identification of
      groups more vulnerable to infant malnutrition. POPULATION AND METHODS: This is a
      cross-sectional study, with a sample of 477 children aged 12 to 59 months old
      living in low income census sectors at "Vila Grande Cruzeiro", in Porto Alegre,
      RS. The children were submitted to anthropometric evaluation and their families
      were stratified according to socioeconomic level measured through an instrument
      developed in Chile for urban poor populations and adapted to local conditions.
      Children with weight/age, height/age and/or weight/height below - 2 standard
      deviation from the median of the reference population (NCHS) were considered
      malnourished. RESULTS: The children from families belonging to the lowest
      quartile in the socioeconomic classification had a 3.4 times higher chance of
      having low weight for age, a 2.7 times higher chance of being stunted and a 11.0
      times higher chance of presenting low weight for height, controlling for
      potential confounders. CONCLUSION: The instrument measuring poverty level was
      useful to identify those children with higher risk for malnutrition.

PMID- 14685425
TI  - [Duration of breastfeeding of children visiting a pediatric outpatient unit].
AB  - OBJECTIVE: To observe the time of total and partial weaning as well as the
      alleged causes for precocious weaning of infants seen at the outpatient unit.
      METHODS: 259 mothers of children aged 12-24 months were interviewed at the
      Pediatric Outpatient Unity of Fundacao Santa Casa de Misericordia do Para.
      RESULTS: It was verified that only 3.9 % of the children received cow milk
      (artificial formula) during the neonatal period. Nevertheless, 62.9 % of the
      babies received tea and/or water at the first month of life. The most frequent
      reasons to give them tea or water were colics, flatulation and babies thirst.
      Only 18.5 % of the infants were completely weaned in the first six months of
      life; 62.6 % of them were breastfed during 12 or more months. There was a
      significant improvement in the duration of breastfeeding as compared with a
      previous study conducted 10 years earlier in the same unity. The most frequent
      justifications mothers gave for total weaning in the first semester were "the
      child refused the breast" and "the breast dried out". CONCLUSION: Despite the
      favorable results concerning the duration of breastfeeding, efforts to encourage
      it must continue above all to avoid early use of tea and/or water.

PMID- 14685426
TI  - [Epistaxis as a manifestation of Bernard-Soulier Syndrome].
AB  - OBJECTIVE: To call pediatrician's attention to an infrequent cause of severe
      repetitive epistaxis. METHODS: The authors report a case of Bernard-Soulier
      Syndrome and also make a review of the literature available in MEDLINE from 1970.
      RESULTS: The authors describe a 3 year-old boy with severe repetitive epistaxis
      with hemodinamic repercussions, who required many blood and hemoderivates
      transfusions. Many diagnostic hypotheses had been formulated, until
      macroplatelets were found. This finding enabled the diagnosis of Bernard-Soulier
      Syndrome. A maxillary artery embolization was performed, and the bleedings
      stopped. CONCLUSIONS: Pediatricians should have a high index of suspection in
      children with severe repetitive nasal bleedings to diagnose uncommon causes of
      epistaxis, like Bernard-Soulier Syndrome and other trombocytopaties.

PMID- 14685427
TI  - [Hepatic veno-occlusive disease: report of a case].
AB  - OBJECTIVE: To alert the pediatricians about a disease caused by herbal teas
      considered harmless. METHODS: Report of a case of Hepatic Veno-Occlusive Disease
      in a child and review of the literature (MEDLINE and LILACS). RESULTS:
      Description of a case of a sudden beginning portal hypertension, secondary to
      Hepatic Veno-Occlusive Disease in a 2 year and 5 month-old-patient, coming from
      Cruz Alta-RS-Brazil, after a chronic consumption of herbal tea called "maria
      mole" (Senecio brasiliensis), which contains pyrrolizidine alkaloids, known as
      hepatotoxic. After an adequate treatment, the patient presented a complete
      clinical and laboratorial recovery, and nowadays he doesnt show any symptoms
      anymore. CONCLUSIONS: Prevention of this disease depends on its divulgation among
      physicians and the general population, and the knowledge of toxic effects of many
      "innocuous" teas.

PMID- 14685428
TI  - [The importance of eosinophils in children with bronchial asthma].

PMID- 14685429
TI  - [Does the use of pacifiers lead to a greater ocurrence of intestinal parasites?].

PMID- 14685430
TI  - [Active immunization in adolescence].
AB  - OBJECTIVE: The purpose of this review is to offer updating on recent changes in
      the schedule of active immunization routine in adolescence. METHODS: This review
      covers specialized medical literature between 1985 and 1996, and follows the
      recommendations of American Academy of Pediatrics and Advisory Committee on
      Immunization Practices. RESULTS: Active immunization in adolescents has been
      changed in the few last years. New vaccines have been licensed (varicella,
      hepatitis A), while some old ones have been recommended for routine use
      (hepatitis B) or as a booster dose (MMR, tuberculosis) at adolescence. This paper
      reviews these vaccines and the last recommendations concerning their use in
      adolescents. Special indications of some other vaccines (antiinfluenza,
      antipneumococcus, etc.) are also mentioned. CONCLUSIONS: The most recent
      modifications in the schedule of pediatric immunization routine must be
      considered in the planning and execution of a comprehensive adolescent health
      care delivery.

PMID- 14685431
TI  - [Peripheral blood eosinophils and serum level of eosinophil cationic protein in
      asthmatics].
AB  - OBJECTIVE: Determine the number of circulating eosinophils and serum eosinophil
      cationic protein levels in asthmatics, and the relationship between them.
      METHODS: We studied 26 atopic asthmatics aged 7-16 years divided in two groups
      according to severity of asthma. Eosinophil counts were obtained by multiplying
      leukocyte number by eosinophil percent. Serum eosinophil cationic protein levels
      were determined by fluoroenzymatic method, CAP System, Pharmacia Diagnostics.
      RESULTS: Asthmatics had eosinophil counts (810 +/- 103/mcl) significantly higher
      than non atopic children (158 +/- 30/mcl). Mean eosinophil cationic protein
      levels were higher in severe asthmatics (p < 0,001) and correlated with
      eosinophil counts. CONCLUSIONS: Serum eosinophil cationic protein levels could be
      useful in assessing the allergic inflammation and probably reflect the activation
      of eosinophils.

PMID- 14685432
TI  - [Hypodense eosinophils in blood of pediatric patients with asthma].
AB  - OBJECTIVE: Determine the number of circulating hypodense eosinophils in the blood
      of atopic asthmatics. METHODS: The hypothesis was that hypodense eosinophils, the
      activated cells, were higher in asthmatics than in non-atopic children.
      Granulocytes were separated from mononuclear cells by Ficoll-hypaque. Gradients
      of density were generated through dilutions of Percoll for fractionations of
      cells. RESULTS: Asthmatics had blood eosinophilia (768 +/- 75/mcl) when compared
      to normal control (200 +/- 28/mcl), and higher mean hypodense eosinophils (39%)
      as compared to normal children (11.7%). CONCLUSION: Eosinophils accumulate in
      asthmatic, especially the low density activated variant, suggesting its active
      role in the allergic inflammatory process.

PMID- 14685433
TI  - [A study on protozoan cysts, helminth eggs and larvae in pacifiers].
AB  - OBJECTIVE: Due to the high prevalence of enteroparasitoses among Brazilian
      children and the possible involvement of objects in carrying these diseases, a
      study was conducted to investigate the presence of protozoan cysts, larvae and
      helminth eggs in pacifiers. METHODS: Over the period of March to December of
      1993, 86 pacifiers of zero to seven-year-old children resident in Vila Promessa,
      a suburb in Alfenas, MG, were examined. The investigation of cysts, larvae and
      eggs was made by the microscopic exam of the sediment obtained from centrifuging
      the liquid resulting from washing the pacifiers. The results were evaluated by
      employing the percentile analysis. Along with the examination of the pacifiers,
      an interview was carried out with the people responsible for the children whose
      pacifiers were examined, aiming at detecting how much was known about the
      transmission of intestinal parasitoses and the proper hygiene of pacifiers.
      RESULTS: Among the 86 pacifiers examined, 10 were found to be contaminated
      (11.63%) and presenting eggs of Ascaris lumbricoides, Enterobius vermicularis,
      Trichuris trichiura, Taenia sp and Ancylostomatidae larvae. CONCLUSION: Pacifiers
      were found to be an important means of transmitting intestinal parasites in the
      age range studied what makes it a need to set a proper and persistent sanitary
      policy in fighting intestinal parasitoses.

PMID- 14685434
TI  - [Prevalence of Haemophilus influenzae resistant to ampicillin, cefaclor,
      cefotaxime, chloramphenicol and cotrimoxazol isolated from laboratories in the
      city of Sao Paulo, Brazil].
AB  - OBJECTIVE: To determine Haemophilus influenzae resistant to ampicillin and other
      antibiotics isolated from different clinical specimens. METHODS: Isolates of H.
      influenzae were identified by culture with V and X factors and the aminolevulinic
      test. Nitrocefin was used to detect beta-lactamase (betaLac) production isolates
      were tested for antimicrobial susceptibility by disc diffusion and agar dilution
      methods. Serotype b was assessed by slide co-agglutination. RESULTS: From 245 H.
      influenzae identified, 155 were tested for serotype b, 28% (43/155) of which were
      positive. The global rate of beta-lactamase-positive isolates was 9% (22/245).
      Resistance was similar among serotype b (11.6%) and non-type b H. influenzae
      (9.8%) (p>0.05). No difference on betaLac production was found according to
      specimen's origin or the patients' age. Resistances to other antibiotics (by agar
      dilution and disc diffusion method, respectively) were: chloramphenicol 3.3 to
      7.1%; cefaclor: 1.6 to 3.9% and cotrimoxazol: 9.1 to 10.5%. No resistance to
      cefotaxime has been detected; 63% (5/8) beta-Lac-positive isolates by agar
      dilution showed also resistance to chloramphenicol, compared to 3% (4/118) in the
      ss-Lac-negative group (p<0.001). CONCLUSIONS: H. influenzae ampicillin-resistance
      has shown to be lower than other hospital-based-studies in Sao Paulo, and
      comparable to rates found in healthy carriers. The association between ampicillin
      and chloramphenicol resistance was significant: where this pattern is frequently
      found, the initial therapy for severe H. influenzae infections - like meningitis 
      should include a third generation cephalosporin.

PMID- 14685435
TI  - [Neonatal cholestasis: the delay in referring patients for differential
      diagnosis].
AB  - OBJECTIVE: An efficient treatment of extrahepatic biliary atresia demands that
      the diagnostic differentiation between intra- and extrahepatic neonatal
      cholestasis be performed by the eighth week of life. This study aimed at evaluate
      the age of the patients admitted to a general hospital for differential diagnosis
      of cholestatic jaundice. METHODS: Forty nine children from the Pediatric Service
      at Hospital de Clinicas, in Porto Alegre, have been studied between 1984 and
      1991, according to the protocol for diagnostic elucidation followed by this
      hospital, which includes biliary tract scintigraphy with Tc-99m DISIDA and,
      depending on its results, an wedge or percutaneous liver biopsy. The ages of the
      children have been compared on the occasion of the procedures. Twenty six cases
      have been studied retrospectively and 23, prospectively. RESULTS: Both the
      patients with intrahepatic and extrahepatic cholestasis underwent scintigraphy,
      on average at over eight weeks (age 77.94 +/- 42.98 days) and the
      histopathological study of the liver was performed approximately two weeks after
      scintigraphy. Only six patients (12.8% of the 47 cases) underwent the liver
      biopsy before the first eighth week of life. CONCLUSIONS: A delay was observed in
      referring patients for differential diagnosis of neonatal cholestasis and the
      performance of tests. The need of hospitalization in order to conduct these
      procedures delays even further this diagnosis, which should be concluded by the
      eighth week of life.

PMID- 14685436
TI  - [Non specific bronchial hyperreactivity in infants].
AB  - OBJECTIVE: To evaluate the presence of bronchial hyperreactivity (BHR) in
      Wheezing Babies (WB) and Normal Control Infants (C) employing the methacholine
      (M) bronchoprovocation test (BPT). METHODS: Fifty-one WB and 20 C, all under two
      years old and assisted at the Department of Pediatrics of UNIFESP-EPM, were
      submitted to BPT with M, having pulmonary auscultation as monitoring parameter to
      evaluate PCW (provocative concentration of M causing wheezing). For all tests, M
      diluted in saline at increasing concentrations of: 0.025, 0.125, 0.25, 0.5, 1.0,
      2.5, 5.0, and 10.0 mg/ml was delivered with O2 (5 l/min) by a face mask. It was
      inhaled through the mouth and nose during 2 minutes of quiet tidal breathing via
      nebulizer with 2 ml of solution. RESULTS: None collateral effects were observed,
      except for tachypnea and tachycardia. There was statistically significant
      differences between WB (2.3 mg/ml) PCW value and C (9.2 mg/ml) (p < 0.05). At the
      PCW value of 2.5 mg/ml, 41% of the WB had statistically positive response (p <
      0.05). This was not observed in the group C, when a positive response only
      occurred at the concentration of 5 mg/ml (25%). At this concentration we observed
      a clear cut difference between WB and C (p< 0.05). According to the severity, the
      highest M concentration was observed within the group displaying mild symptoms.
      CONCLUSIONS: We conclude that BPT utilizing PCW may be a good option for
      detecting BHR in young children. It is well tolerated by children, easy and safe
      to perform. Follow-up studies may clarify the real mean of the PCW.

PMID- 14685437
TI  - [Nutritional evaluation of children with cholestatic diseases].
AB  - OBJECTIVE: To characterize the type of malnutrition and to determine the
      usefulness of anthropometric indices in children with chronic liver disease
      (CLD). METHODS: 11 children (aged 5 - 105 mo) with CLD underwent anthropometric
      evaluation when they were clinically stable. The nutritional evaluation was made
      by the determination of Weight/Age (W/A), Height/Age (H/A) and Weight/Height
      (W/E) Z scores. The nutritional evaluation by Waterlow's method was also made.
      The fat and protein body deposits were estimated by triceps skinfold and midarm
      muscular circumference measurements. The analysis of the 24-hour recall was used
      to evaluate the quality and pattern of the feeding. RESULTS: The mean weight /
      age (W/A = -1.18) and height / age (H/A = - 1.26) Z scores were depressed under 1
      SD, whereas mean weight / height (W/H) Z score was normal. The interpretation of
      the nutritional evaluation by Waterlow's method shows normal mean of the weight
      and almost normal mean of the height. Only three patients had normal triceps
      skinfold thickness (TSF) Z score, and the same occurred with five of them with
      the midarm muscular circumference. The quality and pattern of the feeding was
      adequate in only 4 patients. CONCLUSIONS: We conclude that chronic malnutrition
      is common in childhood CLD and that weight/height values underestimate the degree
      of acute malnutrition compared with TSF thickness, most likely because of the
      inflated patient weight caused by organomegaly. The reduction of the triceps
      skinfold thickness best reflected the nutritional impairment of the patients. The
      quality of feeding of the patients was mostly inadequate.

PMID- 14685438
TI  - [Congenital pulmonary extralobar intra-abdominal sequestration].
AB  - Pulmonary sequestration is a rare congenital anomaly characterized by
      nonfunctioning embryonic pulmonary tissue that has no communication with the
      normal tracheobronchial tree. Pulmonary sequestration comprises 0.15% to 6.4% of
      all congenital pulmonary malformations and is divided into intralobar and
      extralobar types. The extralobar sequestration is rare, and comprises only 25% of
      all sequestrations. It is frequently associated with diaphragmatic hernia,
      eventration and other congenital anomalies. The authors report a case of
      extralobar retroperitoneal pulmonary sequestration which presented as adrenal
      tumour. The diagnosis was done by anatomo-pathological examination and no
      associated malformation was detected.

PMID- 14685439
TI  - [Vertebral osteomyelitis in children].
AB  - Vertebral osteomyelitis is an uncommon disease in children, presenting with signs
      and symptoms that, at least initially, make a correct diagnosis difficult to be
      achieved. The authors report five cases of vertebral osteomyelitis in children,
      describing its clinical and laboratory peculiarities. The usefulness of the
      different radiologic studies for the diagnosis and follow up of these patients is
      discussed. We confirm previous reports according to which, with adequate clinical
      and therapeutic management, the prognosis is good for most patients.

PMID- 14685441
TI  - [Childhood acute myeloid leukemia: how are we doing in Brazil?].

PMID- 14685442
TI  - [Acute pneumonia - a theme we should all be studying].

PMID- 14685443
TI  - [The pediatrician and exclusive breastfeeding].

PMID- 14685444
TI  - [Osteoporosis in childhood and adolescence].
AB  - OBJECTIVE: To review recent data concerning osteoporosis and osteopenia in
      childhood and adolescence, focusing on diagnosis, prevention and treatment.
      SOURCES OF DATA: Literature review of Medline and Lilacs databases (1992 to
      2002). SUMMARY OF THE FINDINGS: Childhood osteoporosis is defined and classified.
      Imaging and laboratory diagnostic techniques are emphasized, as well as
      prevention and drug treatment. CONCLUSIONS: Pediatricians should identify the
      risk factors for osteoporosis and guide patients in terms of its prevention and
      treatment.

PMID- 14685445
TI  - [Acute myeloid leukemia in childhood: 15-year experience in a single
      institution].
AB  - OBJECTIVE: To investigate the survival of children with acute myeloid leukemia
      (AML) before and after the introduction of a Berlin-Frankfurt-Munich-83 based
      protocol. To analyze the prognostic impact of age, gender, nutritional status,
      initial white blood cell count and use of etoposide in the remission induction
      phase. METHODS: This partly prospective/retrospective study comprised 83 children
      with AML diagnosed at Hospital das Clinicas, Universidade Federal de Minas
      Gerais, Brazil, between 1986 and 2000. Before 1991, 15 children were treated with
      2-3 pulses of cytarabin plus daunomycin, followed by several
      consolidation/maintenance schemes. From January 1991 to November 1992 a pilot
      study (n = 15) was carried out to test etoposide toxicity in the induction phase.
      Etoposide was randomized from December 1992 to June 1999. RESULTS: Median follow
      up period was 5 years. Initial remission rates were 40 and 66% before or after
      the introduction of the German protocol, respectively (p = 0.11). Induction
      failure was largely due to death caused by infection and/or hemorrhage. The 5
      year estimated probabilities of survival and of continuous complete remission
      were 31+/-5.4% and 49.7+/-7.4%, respectively. All 22 relapses involved the bone
      marrow. Age below 6 years at diagnosis was significantly associated with a poor
      prognosis. Sex, initial leukocyte count, and nutritional variables were not
      significant prognostic factors. The randomized addition of etoposide in the
      induction phase unexpectedly decreased the probability of complete remission at 5
      years. CONCLUSIONS: The introduction of a German-based protocol in 1991
      significantly improved survival and duration of first remission. No plausible
      explanation for the unfavorable effect of etoposide was found.

PMID- 14685446
TI  - [Interobserver agreement in the radiological diagnosis of lower respiratory tract
      infections in children].
AB  - OBJECTIVE: To evaluate the inter-observer agreement of radiological diagnosis of
      lower respiratory tract infections in children. METHODS: Chest X-rays from 60
      children younger than 5 years of age were evaluated by three physicians: a
      pediatric radiologist (PR), a pediatric pulmonologist (PP) and an experienced
      emergency pediatrician (EP). All children had sought an emergency room due to
      acute respiratory infections with apparent lower respiratory tract involvement.
      Observers were blinded to the original diagnostic conclusions, but clinical and
      laboratory data from the initial medical evaluation were provided with each film.
      Variables were grouped into five categories: a) film quality; b) site of
      abnormality; c) radiological patterns; d) other radiographic images; e)
      diagnosis. Inter-observer agreement was assessed using Kappa statistics,
      accepting prevalence-bias-adjusted values (PABAK). compare the prevalence of
      breastfeeding and exclusive breastfeeding during the first six months of life
      among pacifier and non-pacifier users. RESULTS: Kappa values for each of the
      three observer pairs (RP vs. PP, RP vs. EP, and PP vs. PE) were 0.41, 0.43, and
      0.39, respectively. The overall inter-observer agreement was moderate (0.41).
      Agreement on other variables was as follows: regular for "film quality" (0.30);
      moderate for "site of abnormality" (0.48); fair for "radiological patterns"
      (0.29); moderate for "other radiographic images" (0,43); and moderate for
      "diagnosis" (0.33). The overall intra-observer agreement was "moderate" (0.54),
      which is below the agreement values reported by other studies on chest X-ray
      variability. CONCLUSIONS: Inter-observer variability is an intrinsic
      characteristic of the interpretation of chest X-rays, and the diagnosis of lower
      respiratory tract infections in children remains a challenge. Most of our results
      were similar to those previously reported.

PMID- 14685447
TI  - [Promotion of breastfeeding: the importance of pediatricians with specific
      training].
AB  - OBJECTIVE: To study the factors involved in the maintenance of exclusive
      breastfeeding in healthy infants during the first 4 months of life, with emphasis
      on the role of pediatricians. MATERIAL AND METHODS: A longitudinal study was
      carried out with 101 healthy term babies at a pediatrics outpatient clinic in
      Uberaba, state of Minas Gerais, Brazil. The babies were divided at random into
      three groups: G1, receiving advice from a multiprofessional breastfeeding team;
      G2, receiving advice from a pediatrician trained in breastfeeding; and G3,
      receiving advice from a pediatrician with no breastfeeding training. Group
      randomization was confirmed by analysis of variance. The factors involved in the
      type of feeding at 4 months were analyzed by the chi-square test, by analysis of
      variance and by multiple variable analysis. RESULTS: At the end of follow-up,
      Groups 1 and 2 showed similar percentages with respect to exclusive
      breastfeeding. In addition, the percentage of exclusively breastfed babies in
      Groups 1 and 2 was significantly higher than in Group 3 (p = 0.002). The use of a
      pacifier was negatively correlated with exclusive breastfeeding (p = 0.003). More
      maternal schooling increased the chance of exclusive breastfeeding at 4 months (p
      = 0.041). CONCLUSIONS: In this study, a pediatrician who was prepared and
      motivated to encourage breastfeeding performed similarly to a multiprofessional
      breastfeeding team in terms of promoting exclusive breastfeeding until 4 months.

PMID- 14685448
TI  - [Retinol levels in human colostrum: influence of child, maternal and
      socioeconomic variables].
AB  - OBJECTIVES: To determine colostrum retinol levels in breastfeeding women from the
      city of Natal, state of Rio Grande do Norte, Brazil, and to investigate the
      relationship between retinol levels in colostrum and child, maternal and
      socioeconomic variables. METHODS: Forty-two healthy women aged 18 to 39 years
      were evaluated 48 hours after delivery. Socioeconomic, anthropometric, and
      dietary data were collected by means of a questionnaire. Body mass index was used
      to determine nutritional status. The Virtual Nutri software was used to analyze
      data on daily intake of vitamin A. Retinol levels were determined in 2 ml of
      colostrum using high-performance liquid chromatography. RESULTS: Most women were
      of low socioeconomic and educational backgrounds. Vitamin A intake was adequate
      in 55% of the women (mean intake = 1,398.8 micro g RE/day). The mean amount of
      retinol in colostrum was 93.1 51.1 micro gRE/100 ml. No significant differences
      were found in terms of milk retinol levels for the variables income (p = 0.503),
      educational level (p = 0.708) and birth weight (p = 0. 499). However, a
      statistically significant difference was observed for nutritional status during
      pregnancy (0.016). CONCLUSION: The lack of influence of socioeconomic factors on
      colostrum retinol levels suggests the existence of an adaptive mechanism of the
      mammary gland to maintain adequate retinol levels that meet the infantacute;s
      daily needs.

PMID- 14685449
TI  - [Acute exposure to imidazoline derivatives in children].
AB  - OBJECTIVES: To study acute exposure to imidazoline derivatives in 72 children
      younger than 15 years of age, followed-up from January 1994 to December 1999.
      METHODS: This is a retrospective study of 72 patients with age between 2 months
      and 13 years (median 2 years; 25-75% = 1 to 3 years old) exposed to naphazoline
      (N = 48), fenoxazoline (N = 18), oxymetazoline (N = 5) and tetrahydrozoline (N =
      1), through oral (N = 46), nasal (N = 24) or unknown (N = 2) routes. RESULTS:
      Fifty-seven children developed clinical manifestations such as somnolence (N =
      34/57), sweating (N = 20/57), pallor (N = 17/57), hypothermia (N = 16/57),
      bradycardia (N = 13/57), cool extremities (N = 9/57), restlessness (N = 7/57),
      tachycardia (N = 6/57), vomiting (N = 5/57), irregular respiratory pattern and
      apnea (N = 5/57), miosis/mydriasis (N = 4/57). Naphazoline was the active
      ingredient most frequently involved (N = 47), followed by fenoxazoline (N = 5)
      and oxymetazoline (N = 4). The onset of clinical manifestations was rapid,
      beginning within 2 hours after exposure in 32/57 children. Only supportive
      measures were employed, with one child requiring mechanical ventilation after
      accidental naphazoline ingestion. In most of the children resolution of symptoms
      occurred within 24 hours (N = 39/57). No deaths were observed. Patients exposed
      to naphazoline (N = 47/48) presented a higher frequency of clinical signs of
      poisoning in comparison with those exposed to fenoxazoline (N = 5/18) (p <
      0.001). There were no significant differences in the frequency of patients who
      presented clinical manifestations considering the route of exposure [oral (N =
      34/46), nasal (N = 21/24); p = 0.31]. CONCLUSIONS: Most children (especially
      those younger than 3 years) exposed to imidazoline derivatives (especially
      naphazoline) presented early signs of poisoning regardless of the exposure route
      (nasal or oral). The main signs observed were nervous system, cardiovascular and
      respiratory depression. Most children showed complete resolution of the symptoms
      within 24 hours.

PMID- 14685450
TI  - [Inflammatory reaction in the intestinal wall of rats: can intraperitonial urine
      cause damage?].
AB  - OBJECTIVE: To observe the intensity of the inflammatory reaction caused by urine
      on the intestinal wall of rats. METHODS: Experimental model, using 20 Wistar rats
      divided into two groups. All the animals were submitted to abdominal puncture at
      the right inferior quadrant, twice daily for five days. In Group I (control
      group) no substance was inoculated during the procedure, while in Group II (urine
      group), 3 ml of neonatal urine were inoculated. The animals were killed on the
      sixth day. A small-bowel specimen was fixed in paraffin and stained with
      hematoxylin-eosin. Microscopic analysis was performed by the same pathologist in
      all cases for determination of the degree of inflammatory reaction in the
      intestinal wall. RESULTS: All animals completed the experiment. In group I
      (control group) serositis was observed in six animals and enteritis in one. In
      group II (urine group) serositis was observed in nine animals and enteritis in
      four. The groups were similar in terms of the intensity of the inflammatory
      reaction observed (p = 0.1). CONCLUSION: The intra-abdominal inoculation of
      neonatal urine did not produce significant inflammatory reactions in the
      intestinal wall of rats.

PMID- 14685451
TI  - [Occurrence of Haemophylus influenzae B meningitis after the implementation of a
      mass vaccination program].
AB  - OBJECTIVE: To evaluate the incidence of Hib meningitis before and after the
      implementation of a vaccination program in the state of Rio Grande do Sul State,
      southern Brazil, in 1999. METHODS: This retrospective study summarizes all data
      concerning Hib meningitis recorded by the state of Rio Grande do Sul Department
      of Health/Acute Communicable Disease Surveillance Agency between 1995 and 2001.
      All data were analyzed using the chi-square test (statistical significance: p <
      0.005). RESULTS: The decline in the number of cases of Hib meningitis was
      associated with the Hib vaccine coverage in children. From 1995 to 2001 the
      incidence of Hib meningitis decreased 89% (from 1.35 cases/100,000 people in 1995
      to 0.15 cases/100,000 in 2001 (p < 0.01), especially in children younger than 1
      year (p < 0.005). In the same period, Hib meningitis lethality decreased from
      17.8 to 6.7 % (p < 0.01). CONCLUSIONS: The implementation of an Hib meningitis
      vaccination program has nearly eliminated Hib meningitis in the state of Rio
      Grande do Sul. These findings underscore the need to maintain the vaccination in
      children, with a thorough investigation of suspected cases and reporting of
      confirmed cases.

PMID- 14685452
TI  - [Prevalence of serotypes and antimicrobial resistance of invasive strains of
      Streptococcus pneumoniae].
AB  - OBJECTIVE: To determine the prevalence of serotypes and antimicrobial
      susceptibility of invasive strains of Streptococcus pneumoniae and to discuss the
      implications of these findings for vaccine formulation. METHODS: Strains of
      Streptococcus pneumoniae obtained from normally sterile fluids from patients
      admitted with invasive diseases were isolated and identified at the Hospital de
      Clinicas, Universidade Federal de Uberlandia, state of Minas Gerais, and
      forwarded to Instituto Adolfo Lutz, state of Sao Paulo, for further
      identification, serotyping and determination of antimicrobial susceptibility.
      RESULTS: From April 1999 to March 2003, 148 invasive strains of Streptococcus
      pneumoniae were obtained. The age of patients ranged from 1 day to 88.83 years
      (mean: 21.33+/-25.82 years; median: 4.42 years). Eighty-four (56.7%) patients
      were male. The most common diagnoses were pneumonia (91 cases; 61.4%), meningitis
      (32 cases; 21.6%) and occult bacteremia (15 cases; 10.1%). Strains were isolated
      mostly from blood (76 occasions; 51.3%), pleural fluid (39 occasions; 26.3%) and
      cerebrospinal fluid (30 occasions; 20.2%). There were 23 different serotypes, and
      the most common were 14, 3, 1, 5, 6A, 6B and 18C. Among 30 (20.2%) oxacillin
      resistant strains, 23 (15.5%) were confirmed as resistant to penicillin (12.8%
      intermediate resistance and 2.7% full resistance). Oxacillin-resistant strains
      were restricted to serotypes 14, 23F, 19A and 6B. Resistance to penicillin varied
      with age, being more common in children under two years of age (p = 0.0008). We
      observed decreased sensibility to sulfamethoxazole-trimethoprim (92 isolates;
      63.4%), to erythromycin (12 isolates; 8.3%), to clindamycin (12 isolates; 8.7%),
      to ofloxacin (one strain; 0.8%) and to cefotaxime (three strains; 2%; also
      resistant to penicillin). All isolates were susceptible to chloramphenicol,
      rifampin and vancomycin. CONCLUSIONS: The decreased susceptibility to penicillin,
      detected in 15.5% of the strains was predominant in children under two years of
      age. There were 23 different Streptococcus pneumoniae serotypes. The 23-valent
      polysaccharide vaccine covers 82.6% of the serotypes and 90.2% of the invasive
      strains isolated in this population. In addition, 46.7% of the serotypes and
      63.6% of the strains isolated from children until five years of age are covered
      in the currently available 7-valent conjugated vaccine (PN CRM7).

PMID- 14685453
TI  - [Comparison between an upper airway obstruction score and airway endoscopy to
      detect airway injury associated with endotracheal intubation in children].
AB  - OBJECTIVE: To compare an upper airway obstruction score vs. airway endoscopy to
      detect moderate or severe airway injury associated with endotracheal intubation
      in children. METHODS: Prospective study. Airway endoscopy and clinical evaluation
      were performed after extubation. Airway injuries identified on endoscopy or
      according to the upper airway obstruction score were classified as minor,
      moderate or severe. The obstruction score was assessed in terms of sensitivity,
      specificity, positive and negative predictive values and likelihood ratio to
      detect moderate or severe injuries. RESULTS: Among 215 patient, endoscopy was
      normal in 10.2%. Minor lesions were diagnosed in 54.9% of the patients, followed
      by moderate (24.2%) and severe (10.7%) lesions. In 163 patients with upper airway
      obstruction, the score classified injuries as minor in 23.3%, moderate in 41.4%
      and severe in 11.2%. A score > or = 4 had a sensitivity of 73.3% (95% CI: 67.4
      79.2) to detect moderate or severe injuries and a specificity of 58.6% (95% CI:
      52.0-65.2) to exclude patients without moderate or severe lesions. The positive
      predictive value of a score > or = 4 was 48.7% (95% CI: 42.0-55.4). In patients
      with a score < or = 3 the chance of not presenting moderate or severe injuries
      was 80.4% (95% CI: 75.1-85.7). The probability of a patient with moderate or
      severe injuries to present a score > or = 4 was 73.3% compared to patients
      without those injuries (41.4%) (1.8 fold higher). CONCLUSIONS: The score reliably
      ruled out moderate or severe airway injury in patients with minor upper airway
      distress. On the other hand, scores > or = 4 presented a low specificity.
      Clinical evaluation can be useful to rule out patients with minor airway
      injuries.

PMID- 14685454
TI  - [Maternal and neonatal factors affecting the incidence of bronchopulmonary
      dysplasia in very low birth weight newborns].
AB  - OBJECTIVE: To determine the incidence of bronchopulmonary dysplasia, to identify
      maternal and neonatal factors associated with the disease, and to determine the
      correlation between bronchopulmonary dysplasia and the progress of newborns.
      METHODS: Data were prospectively collected on 153 infants born in Campinas (state
      of Sao Paulo, Brazil) from September 2000 to April 2002 weighing less than 1,500
      g and treated at the University Hospital. The ratio of incidence rates with 95%
      CI, Breslow-Cox regression, Student's t test, linear regression and the Fishers
      exact test were utilized. RESULTS: Among the 124 babies who survived until 28
      days of age, 33 (26.6%) developed bronchopulmonary dysplasia. Birthweight < or =
      1,000 g (5.6; 95% CI 3.0, 10.4) and gestational age < or = 30 weeks (4.0; 95% CI
      2.1, 7.2) were correlated with increased incidence of bronchopulmonary dysplasia.
      Breslow-Cox regression showed that other factors including gender, Apgar score,
      hyaline membrane disease, antenatal steroid therapy, pregnancy-induced
      hypertension, delivery route and maternal age were not associated with
      bronchopulmonary dysplasia. Mean duration of hospitalization and ventilator
      therapy in newborns with and without bronchopulmonary dysplasia was 78.8 days (SD
      = 26.67) vs. 43.0 days (SD = 14.49) (p < 0.01) and 27.2 days (SD = 21.26) vs. 3.7
      days (SD = 3.02) (p < 0.01), respectively. Mean weight gain per day was lower in
      newborns with bronchopulmonary dysplasia (p < 0.01). Mortality in newborns with
      bronchopulmonary dysplasia was 21% (p < 0.00005). CONCLUSION: Gestational age and
      birthweight were inversely proportional to incidence of bronchopulmonary
      dysplasia. After the onset of bronchopulmonary dysplasia, newborns with the
      disorder required longer periods of ventilator therapy and hospitalization, and
      presented inadequate weight gain and higher mortality rates than newborns without
      bronchopulmonary dysplasia.

PMID- 14685455
TI  - [Simultaneous onset of steroid-sensitive nephrotic syndrome and type 1 diabetes].
AB  - OBJECTIVE: We describe the case of a boy with steroid-sensitive nephrotic
      syndrome coexisting with type-1 diabetes mellitus. DESCRIPTION: Nephrotic
      syndrome was diagnosed in a boy (age 3 years and 11 months) with generalized
      edema. Marked weight loss (23 to 16 kg), polyuria, polydipsia and weakness were
      observed after three weeks of treatment with prednisone 2 mg/kg/day. Diabetic
      ketoacidosis was confirmed by laboratory tests: hyperglycemia (glucose 657
      mg/dl), glycosuria without proteinuria, acidosis and ketonuria. Therapy with
      insulin and prednisone was started. He was then maintained on a daily dose of NPH
      insulin. At age 4 years and 1 month a new episode of ketoacidosis without
      proteinuria occurred in association with a viral infection of the upper airways.
      At age 4 years and 4 months nephrotic syndrome relapsed, but the child responded
      well to steroid therapy. There was another relapse three months later, when
      prednisone treatment was interrupted. This led to the introduction of
      cyclophosphamide, with good results. Since then, the patient (now 5 years and 6
      months old) has been taking insulin daily and nephrotic syndrome has not
      relapsed. Plasma levels of C3 and C4 and renal function are normal. Hematuria is
      occasionally present. Anti-GAD antibodies (glutamic decarboxilase) are normal and
      anti-islet cell antibodies are positive. HLA antigens: A2; B44; B52; DR4; DR8;
      DR53. COMMENTS: The simultaneous occurrence of steroid-sensitive nephrotic
      syndrome and type-1 diabetes mellitus is rare.

PMID- 14685456
TI  - [The different spectra of cow's milk allergy].

PMID- 14685458
TI  - [Breastfeeding - rethinking the difficulties].

PMID- 14685461
TI  - [A tour of a pediatric emergency department]

PMID- 14685460
TI  - [Pediatric stem cell transplantation: a worthwhile effort].

PMID- 14685462
TI  - [Pediatric cardiopulmonar resuscitation]
AB  - OBJECTIVE: To present the main aspects of pediatric cardiopulmonary
      resuscitation.METHOD: The articles on pediatric cardiorespiratory arrest and
      cardiopulmonary resuscitation were revised, by Medline and Lilacs systems. Books
      and dissertations were also analyzed. Only the most important articles were
      included in this review.RESULTS: The relevant aspects related to diagnosis and
      epidemiology of pediatric cardiac arrest were described. The sequence of actions
      on cardiopulmonary resuscitation were emphasized. The basic and advanced life
      support techniques were described and the age differences were
      highlighted.CONCLUSION: The knowledge of the content of this review provides more
      effectiveness to cardiopulmonary resuscitation. The anoxic period of time of
      children in cardiac arrest can be reduced and a better prognosis can be thus
      achieved.

PMID- 14685463
TI  - [Approach in acute respiratory tract disfunction]
AB  - OBJECTIVE: To present a review of the current diagnostic and therapeutic approach
      to the major conditions found in pediatric emergency department, which course
      with acute respiratory tract disfunction, stressing some clinical and
      epidemiological characteristics that are useful to the pediatrician in the
      differential diagnosis.METHODS: Outstanding articles related to the subject were
      selected after literature review of the last 20 years, using Md Consult, Medline
      and Lilacs databases.RESULTS: Many diseases can produce respiratory disfunction.
      Taking into account only those with acute symptoms, infectious and/or
      inflammatory causes predominate. History, examination findings and at least a
      chest X-ray are almost always sufficient for the diagnosis, but, sometimes other
      complimentary tests are necessary.CONCLUSIONS: If not properly treated, acute
      respiratory emergencies can result in significant morbidity and mortality. Any
      pediatrician taking part in an emergency team has to obtain respiratory
      management skills and knowledge concerning distinctive aspects and severity
      estimation of the several respiratory diseases.

PMID- 14685465
TI  - [Shock therapy in children]
AB  - OBJECTIVE: Review the theoretical bases of the therapeutic approach for
      volumetric resuscitation of the infant in shock and the evolutionary process that
      take to the pharmacological support to the circulationMETHODS: References were
      obtained from computerized searches on the National Library of Medicine
      (Medline), recent review articles and personal files. RESULTS: Shock and septic
      shock is the leading cause of mortality in critically ill patients. The septic
      shock is an extremely complex disease process leading to progressive multiple
      organ failure. Its presentation may be subtle or catastrophic. Successful
      management depends on an understanding of the pathophysiology of the syndrome,
      allowing rapid, appropriate resuscitation. Treatment often requires aggressive
      correction of volume deficit, maintenance of adequate perfusion pressure with
      inotropic and vasopressor, mechanical ventilation and others therapies.
      CONCLUSIONS: The management of the shock in children presents a challenge for the
      pediatrician. Hemodynamic and respiratory instability should be anticipated.
      Management requires multisystemic and careful intervention.

PMID- 14685464
TI  - [Clinical management of upper airway obstruction: epiglottitis and
      laryngotracheobronchitis]
AB  - OBJECTIVE: To present current concepts on diagnosis and treatment of upper airway
      obstruction, mainly related to differential diagnosis between acute viral
      laryngotracheobronchitis and epiglottitis.METHODS: Bibliographic review covering
      the last ten years, using both Medline system and direct research. The most
      relevant articles published about the subject were selected.RESULTS: Viral
      laryngotracheobronchitis is an acute self-limited disease of the upper airway in
      a child, clinically characterized by barking cough, stridor, hoarse voice, and
      upper respiratory symptoms. The disease is diagnosed by clinical signs and
      symptoms. Rarely, if no immediate airway management is needed, radiography of the
      neck may help to exclude other entities that cause laryngeal obstruction. In
      contrast to viral laryngotracheobronchitis, epiglottitis is characterized by
      inflammation of the supraglottic tissues and is caused mainly by Haemophilus
      influenzae type b. A previously healthy child suddenly develops a sore throat and
      fever. Within hours after the onset of symptoms the patient looks toxic,
      swallowing is painful and breathing is difficult. Drooling and cervical
      hyperextension are frequently present. Lateral neck radiograph is rarely required
      to the diagnosis and may delay appropriate management of the airway. Moderate
      viral laryngotracheobronchitis with stridor at rest and retractions should be
      treated with steroids (systemic or nebulized) and nebulized epinephrine. Severe
      viral laryngotracheobronchitis should be treated aggressively while arregements
      are made for endotracheal intubation. The diagnosis of epiglottitis requires
      immediate endotracheal intubation in the appropriate unit (emergency department,
      intensive care unit or surgical unit) and antimicrobial therapy. Alternatively at
      some medical centers children with severe upper airway obstruction have been
      treated with a mixture of helium and oxygen (70 to 80% concentration of helium)
      instead of room air or pure oxygen to avoid intubation.CONCLUSIONS: There are
      different levels of care for patients with upper airway obstruction, depending on
      their clinical presentation. The clinical manifestations of viral
      laryngotracheobronchitis may be confused with the presentation of epiglottitis.
      Despite this observation we believe that differential diagnosis between viral
      laryngotracheobronchitis and epiglottitis rests on clinical grounds.

PMID- 14685466
TI  - [Management of acute seizure episodes and status epilepticus in children]
AB  - OBJECTIVE: The authors make an up-to-date review about diagnosis and treatment of
      the acute seizures and status epilepticus.METHODS: Bibliographic review of
      Medline database including articles published in the last ten years.RESULTS:
      Acute seizures and status epilepticus affect children of all the age groups.
      Acute seizures can either represent the first manifestation of an epileptic
      condition or be an acute symptomatic event. Status epilepticus represents a
      serious cerebral insult determined by various causes. The emergency, neurology
      and pediatric intensive care units should elaborate clinical policy for the
      establishment of precise diagnostic criteria and therapeutic approach. A good
      clinical approach should include immediate life support, monitoring and rational
      drug administration to end up the seizure and reduce morbidity and mortality
      risks.CONCLUSION: The better understanding of the pathophysiology as well as the
      elaboration of a rational clinical policy improved the outcome in these medical
      emergencies.

PMID- 14685467
TI  - [Hypertensive crisis]
AB  - OBJECTIVE: Based on the review of the principal aspects of physiopathology,
      clinical presentation, and differential diagnosis, the article outlines the
      principles for the treatment of hypertensive crises in children, supporting early
      and systematic approach, with better short and long term prognoses. METHODS:
      Electronic research of the medical literature from the last twenty years (1979
      1999) and protocols from intensive care and emergency services from USA and
      Canada were reviewed.RESULTS: Hypertensive crises in children can occur as
      primary presentation or in a child known as hypertensive. The differential
      diagnosis of the most common causes is based on the clinical history, physical
      examination and laboratory and bioimage studies. Renal (post-streptococcal
      glomerulonephritis, acute and chronic renal insufficiency, renal arterial
      stenosis) and cardiac (aortic stenosis) diseases are the most common causes in
      children. The treatment is directed by the clinical presentation: urgency or
      emergency crisis. The most used drugs are presented, together with clinical
      indications and pharmacological characteristics (route of administration, half
      life, side effects). The general principles of treatment are described, improving
      the care of affected children.CONCLUSIONS: The treatment of hypertensive crises
      in children is based on the rational use of antihypertensive drugs for the
      different causes and clinical presentations, and on basic and advanced support of
      the systemic repercussions of the crises.

PMID- 14685468
TI  - [Acute fever without source in infants and children less than 36 months of age]
AB  - OBJECTIVES: The objective of this article is to review current information about
      fever without source in children less than 36 months of age and to discuss the
      practical aspects of diagnosis and management.METHODS: Articles from the specific
      area were reviewed and presented in a practical form with recommendations from
      the authors.RESULTS: Febrile children comprise a substantial proportion of
      ambulatory pediatric visits. The majority of children are less than 3 years old.
      At first examination, there may be considerable overlap in the clinical
      appearance of children with fever due to viral illness, occult bacteremia and
      serious bacterial infection. The authors present the recommendations and
      protocols cited in the literature to assist physicians in managing infants and
      children with fever without source.CONCLUSION: Although many approaches to the
      evaluation and management of the febrile infant exist, no diagnostic protocol or
      therapeutic scheme is optimal for all patients. Pediatricians may individualize
      their management of these patients, depending on their experience, or
      interpretation of the recommendations presented in the literature.

PMID- 14685469
TI  - [Fluid and electrolyte disorders]
AB  - OBJECTIVE: To review the major concepts involving electrolyte disorders in
      pediatrics, with special emphasis on the diagnosis and treatment.METHOD:
      Systematic literature review, searching through classic pediatric textbooks,
      periodic electronic databases, such as Medline, Lilacs and other sources.
      RESULTS: Electrolyte disorders are among the most common events in pediatric
      medical practice, specially in emergency care, where, depending upon the
      magnitude, they may represent significant risk to patient life or to the
      development of permanent sequelae. Dehydration, independent of etiology, has its
      importance defined by the severity of water deficit (mild, moderate or severe)
      and by the proportion of sodium waste in relation to water deficit (isotonic,
      hypotonic and hypertonic), and should be correctly recognized to guide adequate
      treatment. Sodium disorders have major risks of central nervous system compromise
      and potassium disorders are specially linked to cardiac arrhythmia, always
      deserving special attention and care. On the other hand, calcium, phosphorus and
      magnesium disorders are more related to neuromuscular function alterations and,
      although less threatening, they need adequate recognition and
      management.CONCLUSION: Knowledge of the several mechanisms involved in water and
      electrolyte metabolism is crucial to the correct comprehension, diagnosis and
      management of fluid and electrolyte disorders in pediatrics.

PMID- 14685470
TI  - [Acid-base balance disorders]
AB  - OBJECTIVE: Review the theoretical bases on the maintenance of the acid-basic
      balance, the pathophysiology of the disturbances and its therapeutics in the
      child.METHODS: References were obtained from computerized searches on the
      National Library of Medicine (Medline), recent review articles and personal
      files.RESULTS: Acid-basic disturbances are frequently found in critical ill
      children. Their pathophysiology and main causes are a complex and multifactorial
      process. The management depends on precocious diagnosis and of the understanding
      of the base cause. The treatment should be adjusted for each disturbance and its
      base cause. Frequently it requests an aggressive correction and continuous
      monitoring.CONCLUSIONS: The knowledge of the physiology of the acid-basic balance
      as well as the understanding of the pathophysiology of the main disturbances
      associated to the clinical situations represent a challenge for the pediatrician.
      The management of acid-basic balance demands appropriate and careful
      intervention.

PMID- 14685471
TI  - [Acute poisoning in children]
AB  - OBJECTIVES: To review the literature, covering the most important aspects of
      management of acute poisoning.METHODS: The most relevant articles on the
      management of acute poisoning were selected.RESULTS: Acute poisoning is an
      important matter of public health, particularly for the child. Medicaments are
      the main responsible agents followed closely by accidents with poisonous animals
      and household chemical products, pesticides and industrial products. The
      management of the poisoned patient must proceed through the following sequential
      stages: initial clinical evaluation and stabilization of the patient, when life
      threatening situations are identified and treated; recognition of the toxic
      syndrome and identification of the causal agent, when the careful analysis of the
      signs and symptoms help choosing the diagnostic tests; decontamination, with the
      careful use of the available methods; administration of antidotes, which are
      small in number and should never delay the other phases; enhancing the
      elimination of the absorbed toxic, which requires knowledge of the kinetics of
      the toxic substance; and supportive treatment.CONCLUSIONS: The recognition of the
      toxic syndrome and knowledge of the phases of management are basic conditions for
      the success of treatment.

PMID- 14685472
TI  - [Venomous animal accidents in childhood]
AB  - OBJECTIVE: To highlight the importance of venomous animal accidents in childhood.
      The conducts are based on the proposals of the Ministerio da Saude do Brasil
      [Ministry of Health of Brazil] to standardize medical care in this kind of
      accident. This article shows the importance of early clinical diagnosis and
      assistance.METHODS: Review of international and national literature that includes
      original articles, official standards and books.RESULTS: Pediatricians may always
      feel insecure when they have to attend children who had venomous animal accidents
      because this kind of pathology is not very common. This article tries to offer
      easy guidelines and describes the main steps to be followed. Besides, peculiar or
      unusual aspects of these accidents are to be found in the literature referred to
      in the end of this article. Venomous animal accidents are always more severe in
      children, therefore resulting in higher mortality and sequelae. We assert that
      the early antivenom sera is extremely helpful.CONCLUSIONS: The systematization of
      the assistance may guarantee that the essential steps are followed thus making
      the assistance itself more effective. This is the purpose of the guidelines
      presented in this article.

PMID- 14685473
TI  - [Anaphylaxis and allergic reactions]
AB  - OBJECTIVE: To review the etiologic factors, pathophysiology and specially the
      therapeutic management of the anaphylactic reactions.METHODS: The bibliographic
      review included textbooks of allergy and intensive care and Medline
      references.RESULTS: Anaphylactic reactions that result from the rapid release of
      potent pharmacologically active mediators from mast cells or peripheral blood
      basophils may involve several organ systems with some risk of death.COMMENTS:
      Anaphylaxis is a clinical syndrome with significant mortality rate. There are
      several etiologic factors that trigger the process and multiple pathophysiologic
      mechanisms involved. Early diagnosis and an effective therapy lead to a better
      prognosis. In the majority of the cases prophylactic measures are needed to avoid
      other episodes.

PMID- 14685474
TI  - [Inicial care in severe pediatric trauma]
AB  - OBJECTIVES: To present objectively the therapeutic aspects for the management of
      child victim of trauma.METHODS: The most relevant articles about the management
      of acute trauma were selected.RESULTS: Children possess great potential for
      recovery after a trauma, however, inappropriate resuscitation is the major cause
      of death preventable.Care in the opening and maintenance of the airways, adequate
      input of fluid to the child victim of politrauma or burns as well as prompt
      diagnosis and effective management to internal bleeding has improved prognosis
      and can reduce mortality considerably. Initial assessment and management of the
      injured child requires immediate procedures towards respiratory failure, shock
      and life-threatening thoracic injuries in order to provide efficient ventilation,
      oxyge-nation and perfusion until definitive treatment is performed.
      Concomitantly, the cervical spine should be protected against new injuries or
      progression of established injury.CONCLUSIONS: Effective actions in order to
      prevent accidents and rigorous laws to protect children and adolescents,
      associated to training and practice of specific procedures to the politraumatized
      child could surely reduce the unacceptable morbi-mortality in our country.

PMID- 14685475
TI  - [Pediatric head injury]
AB  - OBJECTIVE: To present an update on head injury with a review of the literature.
      The authors emphasize the importance of the secondary brain injury prevention and
      describe the basic principles of the treatment, from the site of the accident to
      the intensive care unit.METHODS: Papers and abstracts from the database Lilac in
      the period between 1984 and 1999 and Medline between 1995 and 1999 were reviewed
      as well as textbooks and the Guidelines of the American Brain Trauma Foundation
      1995.CONCLUSIONS: Despite the vast literature on the subject there have been many
      controversies regarding the therapeutic proposals. Prospective studies will be
      required in order to verify their efficacy. Nevertheless, the prevention and
      treatment of the secondary brain injury has been shown to be effective in
      reducing the disability and mortality of the patient with head trauma.

PMID- 14685476
TI  - [Sedation and analgesia at the emergency room]
AB  - OBJECTIVES: To present research data about the adverse effects of pain and
      agitation in the emergency room with the best therapeutic options.METHODS: Review
      of the literature, covering some of the most important studies about analgesia
      and sedation in the emergency room, and pharmacokinetics and pharmacodynamics of
      the most important drugs.RESULTS: The metabolic responses, scales of evaluation
      of pain and anxiety and the different clinical situations in the emergency room
      are presented, inluding also the main drugs to be used.CONCLUSIONS: In the
      situations of stress in the emergency room we should not underestimate the
      clinical situations that cause pain and anxiety.

PMID- 14685477
TI  - [Ethical and legal aspects at the emergency department]
AB  - OBJECTIVE: To discuss ethical and legal aspects of physicians attitudes in
      emergency departments under the light of Brazils codes and laws.METHODS: The
      authors raise questions based upon case reports and comment using the medical
      ethical code, laws that protect children and adolescents, hospitalized children
      and adolescents rights statement and medical federal council decisions.RESULTS:
      The authors discuss child patients' rights and the parents disclosure right; the
      problem of domestic violence and abuse and the physician duty to denunciate this
      kind of practice for the child security and protection; the medical
      responsability even under workplace adverse conditions, as well as the concerns
      related to transportation of patients to another hospital; the dilemma between
      withholding and withdrawing life support measures at the emergency department and
      the prohibition to certificate death in violent death situations; the autonomy
      and decision-making capa-city of adolescent patients and their limitations,
      including violation of confidentiality.CONCLUSIONS: The commentaries presented in
      the article try to explain to the pediatrician how to identify ethical and legal
      conflicts in the emergency department and to prepare him (her) to assume
      attitudes based on codes and legal statements, as well as to respect the
      patient's rights.

PMID- 14685478
TI  - [Acquired immunodeficiency syndrome in children: pathogenesis, prognostic
      markers, and treatment]
AB  - OBJECTIVE: To review recent knowledge about Acquired Immunodeficiency Syndrome in
      children to help pediatricians provide care for these patients.METHOD: We
      reviewed the most recent papers about pathogenesis, prognostic markers and
      treatment of the HIV- infected child.RESULTS: We present the main HIV features
      that may interfere in the pathogenesis of this syndrome and that should be taken
      into consideration when the antiretroviral therapy starts.CONCLUSIONS: Viral
      replication in children is very intense, and the persistence of high levels of
      viral load may be a sign of immunological immaturity. Viral load measurement and
      CD4+ lymphocytes count are important markers of the disease progression. At least
      two drugs should be administered as antiretroviral therapy, which should aim at
      reducing the viral load to undetectable levels. This will slow down the
      progression of the disease and the emergence of resistant viral strains.

PMID- 14685479
TI  - [Dengue]
AB  - OBJECTIVE: To review the literature about epidemiological, clinical and
      preventive aspects of hemorrhagic dengue fever in children, and to provide
      Brazilian pediatricians with an update on dengue METHODS: We reviewed MEDLINE and
      classic texts.RESULTS: Dengue is an arbovirus disease, transmitted by Aedes
      aegypti, a mosquito that feeds indoors and is disseminated in Brazil. Its
      clinical presentation ranges from asymptomatic forms to acute disease with fever,
      myalgia, headache and rash. Evolution with hemorrhage, hemoconcentration,
      decreased platelets and shock is characteristic of dengue shock syndrome.
      Mortality rate is high, chiefly in children, if not treated earlier. There is no
      specific antiviral treatment, but a polyvalent vaccine is presently being
      evaluated.CONCLUSION: Among the prevalent acute infectious diseases in our
      setting, dengue is one of the most frequent, and may be highly lethal if
      associated with shock. Vector control is still the most effective prophylactic
      measure.

PMID- 14685480
TI  - [Congenital and perinatal infections]
AB  - OBJECTIVE: To review current information about congenital and perinatal
      infections, mainly related to their epidemiology in Brazil, mother-to-infant
      transmission, diagnosis, treatment and prevention. Particular aspects related to
      the agents T. pallidum, hepatitis B virus, human immunodeficiency virus,
      cytomegalovirus and T. gondii were considered. METHODS: The main published papers
      from the last 10 years were selected from a Medline database electronic search.
      RESULTS: Congenital or perinatal infections can occur in up to 10% of newborns.
      Although there are few Brazilian studies, available data suggest their relevance,
      mainly related to the occurrence of infection due to T. pallidum, HIV and CMV. At
      least 50% of the infected newborns are asymptomatic. However, because these
      infections may lead to long term sequelae, it is necessary to early identify
      infected pregnant women in order to implement specific preventive measures.
      Presently, laboratory methods for early diagnosis of fetal or neonatal infections
      are available. They are predominantly based on assays for detection of IgA or IgM
      specific antibodies and fragments of the microorganism nucleic acids by
      polymerase chain reaction. The available treatments had only limited success,
      because they often have failed to substantially modify the prognosis for infected
      infants. New treatments and outcome studies are needed. CONCLUSIONS: Congenital
      and perinatal infections are a relevant problem whose main current advances are
      related to prevention and laboratory diagnostic methods applicable to pregnant
      women, fetus or infants.

PMID- 14685481
TI  - [Pediatric nosocomial infections]
AB  - OBJECTIVE: Considering that the nosocomial infections have been a serious problem
      of public health all over the world in both developed and developing countries,
      this revision has the aim of amplifying the pediatrician's knowledge, in
      different interfaces of the question. METHODS: A review of the articles from the
      specific literature of the area leading to a practical presentation of the topics
      as well on the personal experience of the writers, who work in this area.
      RESULTS: We have characterized which topics are important when dealing with
      nosocomial infection as, for example, the concepts used in nosocomial infections,
      the methods of epidemiological surveillance, the nosocomial infections in
      pediatric critical areas as the intensive care and the neonatal units, the
      techniques of isolation and precaution, ending with general and specific
      preventive actions. CONCLUSION: Technical knowledge about the central questions
      in nosocomial infections should be basis for a conscious and responsible
      involvement of all the professionals in the health area to control and prevent
      these infections.

PMID- 14685482
TI  - [Bacterial meningitis - diagnosis and treatment]
AB  - OBJECTIVE: To present new concepts on diagnosis and treatment of bacterial
      meningitis regarding etiologic agents, pathophysiology and options about
      antimicrobial, antiinflammatory and supportive therapy. METHODS: Bibliographic
      review from MEDLINE data including articles published during the last ten years.
      One classic article published before this period and chapters of textbooks on
      infectious diseases were also included. RESULTS: Initial empirical antibiotic
      therapy is chosen according to probable etiologic agents for the age group. In
      the CSF microbiological analysis, the gram stains can reveal bacteria in 50% to
      80% of the cases and the culture in nearly 85%. The tests for detection of
      bacterial antigens are useful for the diagnosis but they present low sensitivity.
      The most common agents during the neonatal period continue to be E. coli,
      Streptococcus B and L. monocytogenes. Beyond this period, the incidence of
      meningitis by Haemophilus influenzae b had a significant decrease after the
      introduction of conjugate vaccines. However, S. pneumoniae and N. meningitidis
      continue to be frequent agents. Currently, the thirdgeneration cephalosporins,
      ceftriaxone or cefotaxime, are the antibiotic therapy of choice. They are used
      with ampicillin up to two months of life and alone beyond this age. Dexamethasone
      has showed to be effective in reducing the inflammatory response and the
      sequelae, mainly the auditory sequelae. The fluid restriction doesn't offer
      advantages in the supportive care. CONCLUSIONS: Early diagnosis and prompt
      treatment are related to good outcome. The new insights on pathophysiology, the
      new antibiotics and the increasing bacterial resistance have determined changes
      in treatment.

PMID- 14685483
TI  - [Neonatal sepsis: diagnosis and treatment]
AB  - OBJECTIVE: Review the literature on diagnosis and treatment of neonatal sepsis.
      METHODS: The most important articles on neonatal sepsis were selected through
      MEDLINE. RESULTS: The present review analyzes the different methods of diagnosis,
      laboratory and clinical, as well as the different therapeutic managements of
      neonatal sepsis. CONCLUSION: Neonatal sepsis is a severe disease that must be
      diagnosed early and properly treated in order to avoid lethal outcome.

PMID- 14685484
TI  - [Acquired toxoplasmosis]
AB  - OBJECTIVE: The aim of this review is to present some important aspects of
      acquired toxoplasmosis to the pediatric practitioner. METHOD: All the articles
      about acquired toxoplasmosis published during the last decade and indexed in the
      Index Medicus were revised. From each one, interesting aspects were critically
      selected. RESULTS: We describe aspects of the epidemiology, pathogenesis,
      clinical manifestations, diagnosis, treatment and prevention related to acquired
      toxoplasmosis. CONCLUSION: The content of this article may facilitate the
      management of patients suspected of having acquired toxoplasmosis.

PMID- 14685485
TI  - [Active and passive immunization against acute viral hepatitis]
AB  - OBJECTIVE: The authors present the main indications related to the use of passive
      and active immunization against acute viral hepatitis, specially the composition,
      characteristics and current aspects of hepatitis A vaccination. Measures for
      hepatitis B prevention are also discussed. METHODS: The most recent and relevant
      articles published about the subject were selected and the special aspects of the
      immunological response, through different pediatric ages, are shown. RESULTS: The
      text analyzes the general measures for prevention of hepatitis A using the two
      inactivated vaccines, and also summarizes the indications and composition of the
      hepatitis B vaccines. CONCLUSIONS: Literature provides the guidelines for active
      and passive immunization against viral hepatitis and the present review is an
      update in the subject.

PMID- 14685486
TI  - [Penicillin-resistant pneumococcus: practical implications]
AB  - OBJECTIVE: To review epidemiological, laboratorial and clinical aspects of the
      penicillin-resistant pneumococcus, and to consider the impact of the rapidly
      increasing drug-resistance on the management of the main infections caused by
      these pathogens. METHODS: Bibliographic review covering the last ten years, using
      both Medline system and direct research. RESULTS AND CONCLUSIONS: The
      Streptococcus pneumoniae is an important agent in acute otitis media, pneumonia
      and meningitis in children. The clinical evaluation of the pneumococcal
      infections depends on the age and health condition of the patient, site and
      severity of the infection and the adequacy of the treatment. Penicillin was
      uniformly effective against pneumococcus until three decades ago, when the first
      reports of clinical resistance were published. Since then, there has been a
      rapidly increasing in the level and rates of resistance to penicillin, which
      parallels to others beta lactams and antimicrobials. This paper includes a
      suscint review of the genetic and phenotypic mechanisms of the resistance to
      penicillin, the available bacteriologic tests for determination of in vitro
      susceptibility to antimicrobials and finally the importance of the pneumococcus
      in acute otitis media, pneumonia/bacteremia and meningitis. There has been new
      empirical therapeutic regimens recommended for meningitis, according to the
      community rates and levels of resistance to beta lactams and to the presence of
      certain underlying conditions among the patients, such as immunedepressant
      diseases and frequent antibiotic consumption. The rapidly increasing prevalence
      of drug-resistant strains emphasizes the importance of judicious antibiotic use
      and the development of a conjugate vaccine, effective to prevent invasive
      infections and to reduce the rate of carriage of the pneumococcus, even among
      infants.

PMID- 14685487
TI  - [Rotavirus: clinical features and prevention]
AB  - OBJECTIVES: This report was prepared with the main objective of making an
      extensive review of both clinical features and prevention of rotavirus
      gastroenteritis. In addition, it provides an evaluation about the potential for
      introduction of the tetravalent rhesus-human reassortant rotavirus vaccine (RRV
      TV) in the developing countries. METHODS: The main source of information was the
      most relevant articles published in both national and international journals, as
      well as selected official reports from the World Health Organization. With regard
      to rotavirus vaccines, particular emphasis has been placed on the results
      available from studies carried out during the past five years. Notice we have
      stressed the epidemiological features of rotavirus infections in Brazil. RESULTS:
      As a background for the main subjects of this report - clinical features and
      prevention - available general information on rotavirus infections are briefly
      discussed in the Introduction. This includes an overview of the etiological
      agent, epidemiology, immunity and laboratory diagnosis. A detailed description of
      the typical symptomatic syndrome is made, as well as of other (unusual) clinical
      manifestations of rotavirus illness. We also discuss the rotavirus candidate
      vaccines that have been evaluated to date, highlighting the most significant
      observations which resulted from field trials with the RRV-TV in several
      countries. The potential for large-scale use of RRV-TV in developing countries is
      also discussed, focusing mainly on the epidemiological characteristics of
      rotavirus disease in these regions. CONCLUSION: Rotaviruses are the leading cause
      of severe gastroenteritis in infants and young children in both industrialized
      and lessdeveloped countries; in the latter regions, rotavirus diarrhoeal disease
      represents a major cause of mortality. There is currently a consensus that
      attempts at prevention need to be directed toward the development of an effective
      rotavirus vaccine, for large-scale use, that would primarily protect children
      (aged 0 to 2 years) against severe rotavirus gastroenteritis. In this regard,
      results from a recent reevaluation of the Peruvian and Brazilian lower-titer RRV
      TV efficacy data are promising. Although the RRV-TV ("Rotashield(R)") (recently
      licensed for general use in U.S.A.) seems to be currently the most promising
      rotavirus vaccine, it has been suggested that further trials with this vaccine
      should be conducted in Africa and Asia (efficacy studies) and Latin America
      [immunogenicity and effectiveness (efficacy under real conditions in a given
      setting)]. In addition, it is of paramount importance to establish in these
      regions a surveillance system to monitor the circulating rotavirus strains.

PMID- 14685488
TI  - [Streptococcal infections]
AB  - OBJECTIVES: To review the main diseases caused by the different strains of
      streptococcus, and to discuss the practical aspects of clinical diagnosis and the
      range of therapeutic treatments. METHODOLOGY: A review of the literature and a
      selection of the most meaningful themes for the pediatricians. RESULTS: The
      majority of the streptococcus described here are susceptible and have sensibility
      to penicillin. Different kinds of treatments aim at a better support to the
      offered scheme, including smaller amounts of doses per day, short-lived treatment
      and lowcost. CONCLUSION: Streptococcus infections are very frequently seen in the
      pediatrician's office. It is important to make an accurate diagnosis, and if
      possible a more simplified therapeutic treatment.

PMID- 14685489
TI  - [Infectious mononucleosis]
AB  - OBJECTIVE: To present updated aspects of the Infectious Mononucleosis caused by
      the Epstein-Barr Virus. MATERIALS AND METHODS: Research of bibliographic
      references through the Medline and direct research of selected papers. RESULTS: A
      concise approach to some aspects related to the epidemiology of the virus, namely
      the two types that are presently known,EBVtypeAandEBVtype B, and some differences
      that they present. It was possible to establish a relationship between what one
      sees in the clinical picture and the immunological changes that occur at the same
      time. The author also describes the physiopathology, clinical features,
      complications and other syndromes associated to the EBV. As far as the laboratory
      workup is concerned, it is important to have a complete blood count as the first
      step, followed by the quantitative exam of the heterophile antibodies and
      antibodies antiEBV analysis. CONCLUSION: The pathologies related to the EBV are
      important, and certainly fascinating from the immunological point of view. Among
      these, the Infectious Mononucleosis caused by the EBV has shown some interesting
      clinical and laboratorial aspects.

PMID- 14685490
TI  - [Varicella: clinical aspects and prevention]
AB  - OBJECTIVE: To present, in practical form and updated terms, the clinical aspects
      of the varicella and its prevention using either vaccination or isolation
      precautions. METHOD: Review of the literature using MEDLINE and LILACS referring
      to the last 10 years; presentation of the most recent aspects in the literature
      as well as reference to the author's professional experience in the area.
      RESULTS: Current aspects of the clinic and treatment of this disease are
      analyzed. The vaccine is examined in relation to the soroconversion and safety.
      The technique of application of the vaccine is presented, considering its
      indication for healthy children, adults, seniors and high risk patients. Among
      these, we consider those with leukemia, solid tumors, nephrotic syndrome, AIDS,
      and those transplanted. The application of the vaccine is analyzed in relation to
      contacts, personal in the health area and people in closed communities.
      Precautions, contraindication, production and types of vaccines are analyzed. The
      association and combination of vaccines, as well as their current indications are
      carefully discussed. As a nosocomial infection, varicella requires much attention
      due to its very easy dissemination. Recommended procedures are indicated for both
      hospitalized and contact cases of varicella or zoster. CONCLUSIONS: The
      appropriate knowledge of the clinic, treatment and preventive procedures in cases
      of varicella is mostly important for the pediatrician, especially with the
      introduction of its vaccine in our country.

PMID- 14685491
TI  - [Practical aspects of human rabies prevention]
AB  - OBJECTIVE: To analyze the rabies situation in Brazil, and to study the indication
      and the most adequate postexposure therapy for human rabies prophylaxis according
      to the following factors: kind of accident; animal that causes the accident;
      rabies situation in the geographic area; possibility of observation or
      laboratorial analyses of the animal; availability of immunobiologics METHODS:
      Bibliographic review of the last years and analyses of the main technical
      official reports in the world, including those from the World Health
      Organization, from Brazil Health Ministry, the State Department of Health of Sao
      Paulo, and so on. CONCLUSIONS: The number of cases of human rabies in Brazil has
      been decreasing since the eighties; however the number of post exposure therapy
      is very high due to the inadequate program of rabies control in animals, mainly
      dogs and cats. The most common vaccine used is the Fuenzalida-Palacios. More
      modern and safe vaccines are only available in private clinics. In public health
      centers, it is available exclusively for special patients like the
      immunodeficient ones or those who present adverse reaction to the Fuenzalida-
      Palacios. The other drug used in preventive therapy is the equine rabies
      immunoglobulin which is presently a safe product. The option to this drug is the
      human rabies immunoglobulin - very expensive and not easily available. This drug
      is not indicated in Brazilian public health centers, unless there is risk of
      anaphylaxis for the patient with the use of the equine immunoglobulin

PMID- 14685492
TI  - [Immunization schedule: dynamics and updating]
AB  - OBJECTIVES: The objective of this article is to make an analysis of the dynamics
      of the imunization schedule and an updating of the practical aspects of the
      vaccination. METHODS: The authors, based on the official recommendations, in the
      imunization schedule of the Infectology Department of the Brazilian Society of
      Pediatrics and on their experience, present practical aspects to facilitate the
      understanding of the dynamics of application of the calendar. RESULTS: The
      current calendar of the Brazilian Society of Pediatrics (SBP) is presented with a
      practical analysis of the vaccines BCG, hepatitis B, poliomyelitis, Haemophilus
      influenzae type b (Hib), DPT and triple viral, which are also part of the
      Calendar of the National Program of Immunizations. Besides this, they analyze two
      other suitable vaccines for SBP, against varicella and hepatitis A. Finally they
      comment on the risk of urbanization of the yellow fever and the increasing
      indication of vaccination against this disease in Brazil. CONCLUSIONS: The
      imunization schedule should be dynamic, adapted to the epidemiologic
      characteristics of each country or place. The presented calendar is what is now
      recommended by the Infectology Department of the Brazilian Society of Pediatrics
      (SBP).

PMID- 14685494
TI  - [Varicella in Brazil - importance and epidemiology]

PMID- 14685493
TI  - [What to expect from a health journal?]

PMID- 14685495
TI  - [Qualitative and quantitative methods in biomedical research]
AB  - OBJECTIVE: To describe the main characteristics of the qualitative and
      quantitative research methods, to compare their differences, strengths and
      weaknesses, and to review complimentary assumptions. METHOD: Medline search and
      review of textbooks and selected articles. RESULTS: In order to understand the
      world where he lives, man organizes investigations along with philosophy, with
      religion and, in the last centuries, with science. The two principal paradigms of
      science adopt different research strategies. The quantitative paradigm, dominant
      in biomedical research, uses methods adopted from the physical sciences,
      epidemiology and statistics. These methods are used deductively, and aim to
      generate measures that are objective, reliable and generalizable. The qualitative
      paradigm uses methods that are common to anthropology, and are most conducted for
      discovery, identification, qualitative description, and explanation-generation.
      Each methodological approach has its own strengths and limitations, and it is the
      nature of the research question that will determine which approach is preferable.
      In many circumstances, the use of both approaches is necessary, as complimentary.
      CONCLUSIONS: Although qualitative methods are poorly known by many investigators,
      particularly by physicians, they are not new to medicine. In fact, medicine is
      based on qualitative methods, and both investigators and practitioners should use
      multiple methodologies in order to achieve better health and quality of life for
      their patients.

PMID- 14685496
TI  - [Current role of therapeutic heart catheterization in pediatric cardiology]
AB  - OBJECTIVE: Cardiac catheterization has begun to be employed for therapeutic
      purposes since the middle sixties. In this paper the authors review the current
      indications, technique and results related to each of the interventional
      procedures. It also includes a brief sample of the Instituto Dante Pazzanese
      experience for illustrative purpose. METHODS: The main procedures that are
      addressed include balloon and blade atrial septostomy (Rashkind and Park
      procedures), pulmonary valvuloplasty, aortic valvuloplasty, mitral valvuloplasty
      (for rheumatic mitral stenosis), angioplasty for coarctation of aorta with or
      without stent implantation, angioplasty for pulmonary artery stenosis with or
      without stent implantation, percutaneous occlusion of the patent ductus
      arteriosus, percutaneous occlusion of atrial septal defects and balloon dilation
      of stenosed Blalock-Taussig shunts. The authors make a review of the most
      important papers published in the literature about Interventional Pediatric
      Cardiology, including their own experience. RESULTS: Good or excelent therapeutic
      results are achieved for pulmonic stenosis, coarctation of aorta, patent ductus
      arteriosus, atrial septal defects and pulmonary branch stenosis. Satisfactory
      palliations are obtained for aortic stenosis, rheumatic mitral stenosis and
      complex congenital heart diseases that require balloon atrial septostomy.
      CONCLUSIONS: Due to the recent technological development, pediatric therapeutic
      heart catheterization makes it possible to treat or palliate about 30% of all
      congenital or acquired heart diseases with encouraging results, sparing some
      patients from the need of cardiac surgery.

PMID- 14685497
TI  - [Diagnosis and therapeutic management of sinusitis in children]
AB  - OBJECTIVE: The authors review the main aspects related to the diagnosis and
      management of sinusitis in children, according to the medical literature.
      METHODS: Literature review. RESULTS: Clinical criteria, microbiology, image
      diagnosis, medical and surgical management are presented, whenever sinusitis is
      considered. CONCLUSIONS: The standardization of the clinical approach in
      children's sinusitis allows optimization of the diagnosis and the appropriate
      subsidiary exams, as well the correct use of antimicrobials and others drugs, or
      surgery in selected cases.

PMID- 14685498
TI  - [Soroepidemiology of Varicella in Brazil - results of a prospective cross
      sectional study]
AB  - OJECTIVES: Varicella has more serious consequences in adolescents and adults.
      Recent reports from Europe and Asia show an increasing number of adolescents and
      young adults being seronegative. As there is only limited data on varicella
      zoster virus (VZV) seroprevalence in Brazil and to facilitate the strategy for
      varicella vaccination we conducted a VZV seroprevalence study in Brazil. METHODS:
      This population-based, cross sectional seroepidemiology study was performed in 4
      different regions of Brazil. The studied population was stratified according to
      gender, age and socioeconomic status. VZV IgG antibodies were analyzed by ELISA.
      RESULTS: 3,879 subjects aged 1-40 years were included into the study. The overall
      anti-VZV seropositivity rate across all age groups and centers in Brazil was
      85.4%. There was a strong age relationship. Especially in the South East and
      South seroprevalence was low in the age group 1-5 years (44.5% and 57.8%,
      respectively) while in the North the rate was 88.9%. Overall, Varicella infection
      was independent of the socioeconomic level, but in the youngest age groups (1-10
      years) seroprevalence rates were significantly lower in the high/medium
      socioeconomic class for most regions. Clinical history of chickenpox correlates
      well with anti- VZV seropositivity with a predictive value of 95.1% CONCLUSIONS:
      In preadolescence a substantial proportion of the Brazilian population is
      susceptible to Varicella infection, and a considerable part of the adolescents
      and young adults remain VZVseronegative and are thus also at risk.

PMID- 14685499
TI  - [Evolution of hematological parameters in a group of children with human
      immunodeficiency virus infection - HIV 1]
AB  - OBJECTIVE: To analyze the evolution of clinical and hematological aspects of the
      children infected with HIV 1. METHODS: Using the CDC criteria, 1994, 37 children
      with HIV infection were selected, followed up at the Immunodeficiency Clinic at
      UNICAMP. The study is longitudinal descriptive. Complete blood count, ferritin,
      serum iron, TIBC and direct Coombs were carried out. RESULTS: The clinical
      category that predominated wasB(45.94%) and categories A and C were equal
      (27.03%). All of them were having antiretroviral therapy. Hypochromic and
      microcytic anemia were seen in 100% of patients up to 12 months of age. There was
      association between anemia and the progression of the disease, both clinical
      (p=0.031) and immunological (p=0.0027) and with lymphopenia too (p=0.033).
      Thrombocytopenia occurred in 10 to 25% of the patients. Low serical ferritin was
      seen in 2.7% of the cases and low serum iron in 11.1%. All the 15 patients
      analyzed had negative Coombs test. There was weight and height reduction in 23.5
      to 45% of the children and 70.3% had clinical manifestations up to 9 months of
      age. During the follow up 13.2% of the patients died. CONCLUSIONS: There was
      association between anemia and lymphopenia with the progression of the disease.
      In relation to the aetiology of the anemia, about 10% can be considered anemia of
      chronic disease. Probably the hematological abnormalities seen in peripheral
      blood are the consequences of loss of control of cellular death mechanism and
      hematopoiesis in individuals infected by HIV 1.

PMID- 14685500
TI  - [The decision to breastfeed: grandmother's view]
AB  - OBJECTIVE: This study is the result of an inquiry into the grandmother's role in
      the decision as well as the duration of her daughter's choice to breast-feed.
      METHOD: This project uses a phenomenological theoretical background which leads
      one to understand breast-feeding based on the view of the grandmother. Thus, this
      project analyzes the discourse of 10 women by using the following guiding
      questions: Howdid you feed your children when they were born? What did you think
      about your daughter's choice to breast-feed? Why do you think your daughter
      decided to breast-feed? RESULTS: The analysis of the discourses as a whole
      reveals that for these women breast-feeding is something intrinsical to a
      mother's role as well as an experience transferred from mothers to daughters.
      This project also reveals that breast-feeding is a family tradition which can be
      influenced by advice and support. CONCLUSION: From this perspective, a new focus
      is revealed by giving advice, supporting and encouraging breast-feeding.

PMID- 14685501
TI  - [Use of prophylactic medication in persistent asthma]
AB  - OBJECTIVE: To assess the proportion of patients with moderate or severe
      persistent asthma who are on prophylactic therapy when first evaluated at a
      specialized outpatient center. METHODS: Descriptive study of 306 patients with
      persistent asthma and ages ranging from four to fifteen years old, seen from
      June/1995 to August/1998, at the Respiratory and Allergic Diseases section of the
      Child and Adolescent Institute, an outpatient reference center located in the
      town of Juiz de Fora (MG), Brazil. Data from the Institute's registry, chiefly
      those related to the use of prophylactic medications, such as inhaled steroids,
      sodium chromoglycate, nedocromil sodium, sustained-release theophylline, long
      acting inhaled beta2-agonist and ketotifen were used to fill in a standardized
      protocol. RESULTS: Of the 306 patients, 87.3% had persistent moderate and 12.7%
      had persistent severe asthma. Only 14.4% were on some kind of controller
      medication. When only the use of inhaled antiinflammatory drugs (sodium cromolyn,
      nedocromil sodium and steroids) was considered, this proportion decreased to
      4.6%. There was not statistical significance (p<0.05) between the use or not of
      prophylactic regimens in relation to gender, weight, height, asthma severity,
      hospital admissions, age of onset, age when first evaluated at the outpatient
      center and household smoking. CONCLUSIONS: The rate of utilization of
      prophylactic regimens in this population of persistent asthmatic patients was
      unsatisfactory, a finding particularly stressed by the low rate of subjects on
      inhaled antiinflammatory drugs. It is necessary to emphasize such measures to
      face the magnitude that asthma represents in our country.

PMID- 14685502
TI  - [Pseudomembranous colitis]
AB  - OBJECTIVE: To alert about the pseudomembranous colitis in children, a consequence
      of the use of antibiotics. METHODS: This report is the result of the clinical
      follow-up of a patient with chronic diarrhea after the use of several
      antibiotics. The bibliography was obtained through Medline system. RESULTS: Case
      report of a girl two years and seven months old, previously healthy, with a
      clinical picture of chronic diarrhea with dysenteric characteristics after the
      use of antibiotics, associated with important weight lost and hypoproteinemia.
      The diagnosis of pseudomembranous was established clinically and was confirmed by
      colonoscopy and the presence of Clostridium difficile toxin A in the stools.
      CONCLUSIONS: It is necessary to consider the C. difficile infection in any child
      with diarrhea associated to the use of antibiotics. The antibiotics in pediatric
      patients should always be prescribed with caution and precise indications.

PMID- 14685503
TI  - [Chronic arthritis in a child with primary agammaglobulinemia]
AB  - OBJECTIVES: To report a case of a child with Bruton's disease and the unusual
      association with chronic aseptic arthritis resembling juvenile rheumatoid
      arthritis. METHODS: A 16 month-old boy was seen at the Pediatric Rheumatology
      unit of HC-UFG and Hospital da Crianca (Goiania- GO). The authors evaluated
      relevant clinical and laboratorial features, including follow-up and response to
      therapy. The data were then compared to previous reports published in the world
      literature based on a Medline search of the subject. RESULTS: Since the age of 6
      months, the patient had recurrent episodes of infection that responded poorly to
      antibiotics. Forty days before admission, he had onset of arthritis in his left
      knee. The diagnosis of Bruton's disease was based on the seric levels of
      immunoglobulins and the response to intravenous gammaglobulin infusions. Besides
      improvement with this therapy, clinical characteristics and other indirect
      laboratorial tests highly suggested the diagnosis of chronic, aseptic arthritis.
      CONCLUSION: We present a case of a rare association between Bruton's disease and
      chronic, aseptic arthritis, very similar to juvenile rheumatoid arthritis. Early
      recognition of this rare aseptic articular involvement is important for early and
      efficient therapy with intravenous gammaglobulin infusions, avoiding unnecessary
      hospital admissions and inappropriate use of antibiotics.

PMID- 14685504
TI  - [Thoracoscopy with mediastinoscope in pediatric complicated parapneumonic
      effusion]
AB  - OBJECTIVE: To evaluate our experience with thoracoscopy with small
      mediastinoscope in complicated parapneumonic effusion in children.METHODS: From
      July 1995 to June 1997, seven children with complicated parapneumonic pleural
      effusion underwent thoracoscopy with mediastinoscope at Hospital de Clinicas de
      Porto Alegre. The procedure was carried out with a small mediastinoscope built in
      our hospital.RESULTS: There were six girls and one boy. The procedure was
      preformed under general anesthesia, without selective intubation. Six patients
      had previous intercostal tube drainage; one underwent thoracoscopy as a primary
      procedure. No complication was observed after the procedure. During follow-up,
      two children underwent pleurotomy due to residual pleural effusion with
      persistent fever; two others presented asymptomatic small pleural
      effusion.CONCLUSION: Thoracoscopy with small mediastinoscope is safe, efficient
      and without severe complications. It is very useful to remove loculated
      complicated parapneumonic effusion at fibrinopurulent stage and to enable lung
      expansion.

PMID- 14685505
TI  - [Imerslund-Grasbeck syndrome: report of two cases]
AB  - INTRODUCTION: The Imerslund-Grasbeck syndrome is a rare hereditary autosomal
      recessive disease, characterized by the onset of megaloblastic anemia and
      asymptomatic proteinuria during the first 2 years of life. OBJECTIVE: To
      emphasize the importance of early detection of this disorder, due to high
      morbidity when not correctly treated, in addition to the necessity of screening
      and genetic counseling of the asymptomatic family members. METHODS: The authors
      report two patients, male and female, 8 and 10 years old, respectively. Their
      past history revealed anemia and multiple blood transfusions since their infancy.
      They evolved with pancytopenia during childhood and diagnosis of Severe Aplastic
      Anemia or Fanconi Syndrome was suspected. They were referred to the Bone Marrow
      Transplantation Section -HC- UFPR. RESULTS: Laboratory investigations revealed
      pancytopenia in peripheral blood. Bone marrow aspiration showed a marked
      megaloblastic erythropoiesis. Twenty-four-hour urine collection revealed
      proteinuria (3.0 and 5.8 g/dl respectively). Cytogenetic analysis was normal.
      Resolution of symptoms followed replacement therapy with parenteral vitamin B12.
      CONCLUSIONS: The presence of megaloblastic anemia in children should be followed
      by investigation of proteinuria, due to the existence of this rare disorder, that
      has a simple diagnosis and an effective treatment.

PMID- 14685506
TI  - [Mortality in adolescents: a threat to the hoped-for improvement in life
      expectancy in Brazil]

PMID- 14685507
TI  - [Etiological diagnosis of infections in the inferior respiratory tract - a
      constant challenge]

PMID- 14685508
TI  - [Critical analysis of respiratory infectious disease investigations related to
      children attending day care centers]
AB  - OBJECTIVE: Social-economic and cultural changes are increasingly leading families
      to share the children's care and education with daycare centers. Nevertheless,
      this practice is being widely criticized. Medical literature, for example, points
      to the high risk of illnesses in these environments. Searching to assess
      theoretical- methodological aspects underlying disease/daycare research, a
      bibliography review was done. METHOD: The last five years production was
      reviewed, through Current Contents, Med-Line and Lilacs, using creche / daycare
      center as keywords. RESULTS: 665 papers were obtained and organized in subgroups.
      Selecting the group of papers on respiratory infectious diseases, 34 papers were
      obtained, being 22 of them empirical, and 12 theoretical or review article, etc.
      The empirical studies used large populations; data were collected by interviews,
      medical reports and laboratory analyses; 50% were cross-sectional.
      Disease/daycare relation was obtained mainly by quantitative analysis, based on a
      multivariate model and logistic regression. Seventy per cent concluded that
      attending daycare implies an illness high risk, especially for youngers than 2
      years. The papers with a preventive character, and-in more subtler ways - 50% of
      the others point alternative solutions for this clinical and social problem
      (vaccination, immunity stimulation, environmental organization). CONCLUSION: The
      structure and the discussion of the majority of the studies seem to be guided by
      implicit assumptions, based on conceptions of an ideal situation of care (at
      house, by the mother). The results are legitimized by large populations and
      sophisticated statistic systems. Nevertheless, they express a prediction risk,
      which highlights static aspects, not the dynamic ones, of health/ disease
      processes. At last, they treat a social problem on clinical individual
      assumptions.

PMID- 14685509
TI  - [Enthesopathy: a symptom seldom recognized by pediatricians]
AB  - OBJECTIVE: The disease in the entheses, which are sites of attachment of tendons,
      ligaments, fascias or joint capsules to bone, may be noted clinically by the
      onset of tenderness or pain associated to digitopression in certain points. This
      revision article aims to draw the attention of pediatricians to the
      enthesopathies or enthesitis (inflammatory disease of these structures) in
      childhood and adolescence. METHODS: The study reviews concepts about the
      structure of the enthesis and the clinical, laboratorial and radiological
      features concerning enthesopathy, as well as differential diagnosis and
      therapeutic measures. Articles and texts concerning the theme were obtained based
      on a research in Medline (available data since 1966) and Lilacs (available data
      since 1981) database, as well as in Pediatric Rheumatology textbooks published
      after 1990. RESULTS: Enthesopathy in children and adolescents appears more often
      in the limbs and seems to be associated to the development of
      spondyloarthropathies, occurring less commonly in other inflammatory diseases or
      even noninflammatory conditions. CONCLUSIONS: The identification of
      enthesopathies is important to the early diagnosis of children and adolescents in
      risk of developing spondyloarthropathies, so that they may be included early in
      an adequate program of physical and drug therapies.

PMID- 14685510
TI  - [Adolescent mortality in the city of Rio de Janeiro from 1981 to 1995: how many
      deaths could be prevented?]
AB  - OBJECTIVE: This paper examines the main causes of mortality among adolescents
      ages 10 to 19 in the city of Rio de Janeiro with a focus on mortality prevention.
      METHODS: Mortality data from 1981 to 1995 were taken from the Mortality
      Information System of the Brazilian Ministry of Health. Age and sex specific
      mortality rates were calculated for the main causes of death covering three
      discrete time periods (1981-85, 1986-90 and 1991-95). RESULTS: Rates of homicides
      and fatal injuries by firearms have increased for adolescents of both sexes
      during the period studied. Among adolescent males the increase was from 46.5
      /100,000 (between 1981 and 1985) to 105.8/100,000 (1991- 1995). Among adolescent
      females, mortality rates attributable to the same external causes presented a
      growth from 3.1/100,000 (1981-1985) to 7.8/ 100,000 (1991-1995). Geographic
      analysis indicates that the harbor area of the city and vicinities reflect higher
      indices of firearmsrelated deaths. For the same time period, non-external causes
      of death declined. Malignant neoplasias and pneumonia, the most frequent non
      external causes of death, are decreasing. The rates of complications involving
      immune deficiencies have increased from nonexistent to 1.2 /100,000 during the
      last period (1991-1995) studied. CONCLUSION: The main causes of deaths among
      adolescents in the city of Rio de Janeiro are preventable. We propose that health
      professionals be attentive to this fact to prevent unnecessary deaths through
      health promotion.

PMID- 14685511
TI  - [Viral infections in hospitalized children affected by acute lower respiratory
      tract disease]
AB  - OBJECTIVE: To evaluate the frequency of the main respiratory viruses in
      hospitalized children affected by acute lower respiratory tract disease at a
      university hospital. METHODS: This is a prospective trial that included two
      cohorts of hospitalized children in the period from April to July 1996. The
      groups were selected according to the presence of lower respiratory tract disease
      on admission: Group A- with acute disease (history of less than 7 days) and B-
      without present or recent respiratory disease. The parameters for defining lower
      respiratory tract disease included physical and/or radiological pulmonary
      changes. Clinical and radiological criteria were established for the
      classification of lower respiratory tract diseases in group A. Nasopharyngeal
      swab was collected from all children on admission for viral detection by cellular
      cultures and direct immunofluorescence. RESULTS: 201 cases were selected, 126 in
      group A and 75 in group B. Viruses were identified in 71 children from
      groupA(56.4%) and only in 3 from group B (4.0%). The predominant agent in group A
      was respiratory syncytial virus, identified in 66 cases; adenovirus (4) and
      influenza (1) were detected in other patients. In group B two patients with
      respiratory syncytial virus and one with adenovirus were identified. The patients
      from group A affected by respiratory syncytial virus were younger (median age 3
      months versus 13 months) and more wheezy on physical examination (78.7%) than the
      other patients of the group (33.3%). This virus was associated to most of the
      bronchiolitis cases (84%) and to half of the pneumonia cases (46.4%). CONCLUSION:
      The authors found a significant presence of viruses in the majority of children
      hospitalized with acute lower respiratory tract disease. The respiratory
      syncytial virus was the predominant agent identified. These results are similar
      to others previously reported both in developed and some developing countries.
      The authors emphasize that the present study evaluated only partially the
      possibility of simultaneous infection by other pathogens and that the present
      protocol was conducted during the season with the highest incidence of
      respiratory syncytial virus.

PMID- 14685512
TI  - [Evaluation of the use of the 10th percentile of weight for age as a cut point
      for detection of children under nutritional risk]
AB  - OBJECTIVE: To evaluate the use of the 10th percentile of weight for age as a cut
      off point for detection of children under nutritional risk, especially for
      programs of alimentary supplementation. METHODS: 841 children with age between 10
      days and 60 months were studied in a primary health care center located in the
      periphery of Ribeirao Preto, SP, Brazil. It was a cross-sectional study that
      included age, sex, weight and height, later computing the z scores of weight for
      age, height for age and weight for height, on the basis of the data of the NCHS.
      Through 2x2 type tables, where the results in relation with the 10th percentile
      (above or below this cut off point) and other indices were compared (above or
      below - 2 z scores), the capacity of 10th percentile of weight for age to detect
      children with various anthropometric deficits was estimated. RESULTS: The false
      negative results were always very low, between 0 and 1%, in opposition to the
      false positive results, that varied from 76.3 to 90.5%. The values of
      sensitivity/specificity have been 100/85.9%; 93.3/83.8%; 82.9/85.7%, respectively
      for deficits of weight for age, weight for height and height for age.
      CONCLUSIONS: The 10th percentile of weight for age was found adequate for
      population screening of children with weight for the age and weight for the
      height deficits (high sensitivity), but these children must be better evaluated
      later on (too many false positive results). For height for age deficits, the 10th
      percentile resulted inadequate.

PMID- 14685513
TI  - [Intrauterine energetic malnutrition in rats: muscle skeletal changes in the 1st
      and 2nd generations]
AB  - OBJECTIVE: To study by histochemical analysis the skeletal muscle in malnourished
      newborn rats submitted to intrauterine malnutrition. METHODS: 90 days old female,
      Wistar EPM-1 rats, with 200 -/+ 20g body weight, malnourished during the
      gestation period were studied. At the 21th day of gestation, muscular biopsy was
      performed in the biceps bracchi of the newborns, obtained by cesarean (1st
      generation). One group of newborn intrauterine malnourished rats had nutritional
      recovery after birth by staying six/lactating rat and by free feeding up to the
      90th day of life, when the females became pregnant and their offspring formed the
      2nd generation. RESULTS: Weight gain during gestation and body weight of the
      newborn were significantly different when each malnourished group was compared to
      its respective control. The muscular biopsies of the malnourished newborns
      presented tissue involvement, characterized by loss of predominance of type II
      fibres, low oxidative activity, lessening of muscular fiber diameter,
      proliferation of intersticial tissue, and edema. In the 2nd generation, the
      newborns presented adequate body weight, but maintained muscular tissue
      involvement, with lessening of predominance of type II fibers, reduction of
      muscular fiber diameter, low oxidative activity, increase of intersticial space,
      necrosis, but without edema. CONCLUSION: The energetic malnutrition affects the
      skeletal muscle at birth, when it occurs during miogenesis, in both 1st and 2nd
      generation, maintaining permanent or temporary lesions in the muscular tissue.

PMID- 14685514
TI  - [Neonatal dermatoses of relevant medical significance: their report in the
      newborn's file]
AB  - OBJECTIVE: To check the report of neonatal dermatoses of medical relevance
      (congenital melanocytic nevus, sebaceous nevus, cafe-au-lait spots, Port-wine
      stain, ash leaf maculas) in the newborn's file. METHODS: The authors carried out
      a cross-sectional study in two hospitals in the city of Belo Horizonte. All
      children born during a consecutive period of 4 months were examined within their
      36 first hours of life by a dermatologist who reported all clinically relevant
      dermatoses (congenital melanocytic nevus, sebaceous nevus, cafeau- lait spots,
      Port-wine stain, ash leaf macules). Simultaneously, the dermatologist's report
      was cross checked with the pediatrician's. RESULTS: Neonatal dermatoses of
      clinical relevance were found in 42 (5.6%) out of 752 children examined during
      this period. However, the report in the neonate's file could be detected only in
      5 (11,9%) out of 42 children. CONCLUSIONS: Clinically relevant dermatoses were
      underreported in the neonate's file in this study. There is a clear need to
      stimulate the detection and report of these skin disorders so that parental
      advice, treatment and genetic counseling can be adequately indicated.

PMID- 14685515
TI  - [Joint effort to improve quality in a Brazilian pediatric public hospital through
      cross-infection control]
AB  - OBJECTIVES: To examine the role of the laboratory in nosocomial infection control
      from January 1993 to December 1996 in Centro Geral de Pediatria of Hospital
      Foundation of Minas Gerais state. METHODS: Follow -up of 101,139 patient-days
      (11,147 discharges + deaths + transfers) in the wards and intensive care unit by
      using the National Nosocomial Infection Surveillance (NNIS) system proposed by
      the Centers for Disease Control and Prevention (CDC- Atlanta). Prospective
      surveillance of nosocomial infections at all sites was performed according to the
      hospital - wide (since 1992) and intensive care unit (since 1996) NNIS
      components. The CDC definitions since 1988 and Brazilian Ministry of Health
      regulation number 930 since 1992 were used to diagnose the nosocomial infections.
      RESULTS: The five most frequent nosocomial pathogens (from a total of 139
      isolates) were Klebsiella sp = 24.5%; S. aureus = 18%; P. aeruginosa = 13.7%; E.
      coli = 12.9%; S. epidermidis = 12.2%. The percentage of identification of
      pathogens isolated from nosocomial infection sites has increased from 6.2% in
      1993 to 13.3% in 1995 and 28.2% in 1996 (p< 0.001) and so has the attempt to
      isolate the pathogens: 7.5% in 1993, 16.1% in 1995, 33.8% in 1996 (p< 0.001). The
      time interval taken for lab results (from specimen collected to microbiology
      result) has decreased from the average of ten days in 1993 to six days in 1996 (p
      = 0.001). CONCLUSIONS: The continuing education and improved communication among
      infection control personnel, pediatricians, surgeons and members of the
      laboratory have proven to play a key role in the epidemiology of nosocomial
      infections by defining their etiologies in the Centro Geral de Pediatria. A task
      force to determine the microbiology has been achieved by the understanding of all
      clinicians that it is important to treat their patients specifically. The NNIS
      method applied to Brazilian hospitals has shown its impact on the microbiology
      lab role in nosocomial infection control as well.

PMID- 14685516
TI  - [Down syndrome associated with clinical manifestations of Kabuki syndrome: report
      of a case]
AB  - OBJECTIVE: To describe an atypical case of Down syndrome presenting with
      additional clinical manifestations that might be components of Kabuki (Niikawa
      Kuroki) syndrome.CLINICAL REPORT: We report the clinical history of a 19-month
      old girl with a 47,XX, +21 karyotype, who presented brachycephaly, flat face,
      long palpebral fissures, eversion of the lateral portion of the lower eyelids,
      arched eyebrows with sparse lateral regions, long eyelashes, epicanthus, cortical
      cataract, small ears, protruding tongue, muscular hypotonia, developmental delay,
      hyperflexibility of joints, brachydactyly, and dermatoglyphic
      abnormalities.CONCLUSION: The diagnosis of Down syndrome was confirmed
      cytogenetically. However, the presence of additional anomalies - mainly in the
      ocular region - suggested that the child might also have the Kabuki syndrome.

PMID- 14685517
TI  - [Urological anomaly in an infant with Soto's syndrome: report of a case]
AB  - OBJECTIVE: To discuss the diagnosis and the etiology of a bilateral urologic
      anomaly in a patient with Soto's Syndrome (cerebral gigantism). To alert the
      pediatric physicians and urologists about the coexistence of these two
      malformations. RESULTS: A three month old boy, born of a 35 week uncomplicated
      first pregnancy by cesarian, with phenotypic, radiologic and metacarpophalangeal
      profile of Soto's Syndrome was admitted to the Hospital because of hyperpnea,
      tachycardia and 39o C recurrent fever. The culture of urine disclosed 500.000
      col/ml. Cistouretrographic study showed bilateral megaloureter and
      hydronephrosis. Vesico-ureteral bilateral reflux was diagnosed and antibiotic
      therapy was administered. Patient's follow up was excellent and was discharged
      taking preventive nitrofurantoin. CONCLUSIONS: As in other cases of urinary tract
      infection, pediatric physicians must consider urologic anomalies in children with
      cerebral gigantism who present the clinical presentation of Soto's Syndrome.
      Autonomic Nervous System development failure in ureteral muscles could be an
      alternative etiology.

PMID- 14685518
TI  - [Hypochondriasis by proxy in children: report of two cases]
AB  - OBJECTIVE: To emphasize important aspects for the diagnosis and approach of
      patients with history of child abuse, related with the Munchausen Syndrome by
      proxy, and its variant, Hypochondriases by proxy. METHODS: The authors describe
      two cases followed in the Pediatric Service in a terciary hospital of Salvador,
      Bahia, in which they found aspects of the medical history and physical
      examination of these children and in the mothers' behavior compatible with
      Munchausen by proxy (Factitious disorder by proxy). RESULTS: In the two cases
      presented, we observed a standard in the clinical history, described as recurrent
      inpatient and outpatient medical support, through the last three years, without
      the identification of abnormal results. These facts do not decreased the
      certainty of the mothers about their children's disease (hypochondriases by
      proxy). Furthermore we observed cooperation on the part of the children by
      incorporating the role of the sick one, which made their school and social
      adaptation more difficult. CONCLUSIONS: The pediatrician must be aware of the
      diagnosis of Munchausen Syndrome by Proxy and its variation, hypochondriases by
      proxy, in those cases of unsuitable and recurrent disease, lack of symptoms and
      signs in the absence of parents, and diagnostic methods with meaningless results.
      When absolutely certain about diagnosis, the physician must establish the risk
      for the child (increased mortality in these cases) and suggest psychotherapy for
      the mother or perpetrator.

PMID- 14685519
TI  - [Anomalous subclavian artery: a group of 15 cases]
AB  - OBJECTIVE: To report clinical presentation, diagnostic procedures and treatment
      of patients with anomalous subclavian artery. SUBJECTS: Fifteen patients with
      anomalous subclavian artery followed up at the Department of Pediatrics, Hospital
      de Clinicas da Universidade Federal do Parana. RESULTS: Age at diagnosis varied
      from birth to eight years, and 10/15 were female. Nine presented with respiratory
      symptoms (cough, pneumonia, stridor, wheezing). Eleven had gastrointestinal
      symptoms (vomiting and choking). Six patients have both respiratory and digestive
      symptoms. Diagnosis was suggested by barium swallow in 14/15; confirmed in 10 by
      arteriography or helicoidal tomography with vascular reconstruction. In fourteen
      cases, the anomalous subclavian was at the right side and in one at the left
      side. Frequent associations were gastroesophageal reflux (6/15), cardiac septum
      defect and Down syndrome (3/15). Surgical repair was undertaken in eight, two of
      whom had chylothorax in the immediate post operative period. CONCLUSION: Although
      anomalous subclavian artery is mostly asymptomatic, it should be looked for in
      children with respiratory symptoms, mainly cough and choking. The chief
      investigation tool is barium swallow, and surgical repair is needed when symptoms
      are present.

PMID- 14685520
TI  - [Research involving children and adolescents]

PMID- 14685521
TI  - [Prolonged esophageal pH monitoring in preterm infants: a challenge]

PMID- 14685522
TI  - [Evidence based medicine: An example in the pediatric setting]
AB  - OBJECTIVE: This paper reviews the main steps to incorporate into clinical
      practice the concepts of evidence-based medicine, which is a strategy to help
      clinicians take more suitable decisions when confronted with clinical problems.
      METHOD: Search in Medline database of articles related with evidence-based
      medicine, review of a number of clinical epidemiology textbooks and selected
      articles. RESULTS: Evidence-based medicine recognizes two main sources of
      information for clinical decision making: 1) the individual patient; and 2)
      clinical epidemiological research. Trough evidencebased medicine the experience
      accumulated by a trained clinician should be integrated with the best external
      evidence obtained from systematic research. The appraisal of external evidence
      requires new knowledge and skills for the practicing clinician. These skills aim
      at enabling the clinician to make independent critical judgement of the quality
      of information that will translate into medical actions for his/her patients.
      Evidence-based medicine provides the tools to 1) keep up with an ever growing
      burden of health information; 2) efficiently select best available information;
      3) critically appraise selected information; 4) synthesize selected information;
      and 5) integrate selected information into clinical experience in the management
      of diagnosed health problems. CONCLUSIONS: Evidence-based medicine could be seen
      as a way to bridge knowledge, skills, and attitudes acquired from clinical
      experience with the ability to evaluate the best available external evidence
      generated by scientific research.

PMID- 14685523
TI  - [Glycogenosis type I]
AB  - OBJECTIVE: To o present up-to-date knowledge about Glycogen storage disease type
      I (GSD-type I) - a disease caused by the deposit of glycogen resulting from the
      deficiency of the enzyme glucose-6- phosphatase - and to provide the
      pediatricians with the necessary information for a precocious diagnosis and an
      adequate conduct for those cases where this metabolic disturbance is present.
      METHODS: Through Medline, the most significant articles published during the last
      20 years were selected from national and international journals of medicine, with
      special attention to dietary treatment of glycogen storage disease type I.
      RESULTS: The metabolism of glycogen and the metabolic consequences of glycogen
      storage disease type I were discussed, especially hypoglycemia, the principal
      metabolic disturbance of the disease. The clinical and laboratory findings are
      described together with the histopathology. The use of uncooked cornstarch and
      enteral carbohydrate infusion are the means used for the maintenance of
      normoglycemia. The control of hyperuricemia, hyperlipidemia and platelet
      disorders are other aspects of the treatment as well as the prevention of
      infections and the use of G-CSF for glycogen storage type Ib. Hepatic transplant
      and its principal indications are commented on. Hepatic adenomae, which always
      have the potential of malignant transformation, are the results of incomplete
      treatment. CONCLUSIONS: Although it occurs rarely, glycogen storage type I is an
      important cause of volumous hepatomegaly which is associated with hypoglycemia
      among the infants. The dietary treatment of this illness has significantly
      altered the clinical course and has improved the prognosis. Therefore it is
      indispensable that the general pediatrician should be familiar with the diagnosis
      of this clinical state so as to act rigorously in favor of the dietary control.

PMID- 14685524
TI  - [Prolonged esophageal pH monitoring utilization in the diagnosis of pathologic
      reflux in neonates]
AB  - OBJECTIVES: To present indications and results of prolonged esophageal pH
      monitoring in diagnosing pathologic gastroesophageal reflux in newborns during
      their stay in the neonatal unit. METHODS: This retrospective descriptive
      analytical study of 85 prolonged esophageal pH monitoring in neonates was
      performed, between October 1995 and March 1998, in a tertiary intensive care
      unity. A Digitrapper MKIII device, pH probes with one or two channels, and
      antimony electrodes were utilized. The probe was placed 3 cm above the
      gastroesophageal junction. RESULTS: The main indications of this esophageal pH
      study were hypoxemia episodes demanding supplemental oxygen, and caffeine
      resistant apnea. The means -/+ SD of birth-weight and gestational age in the
      patients evaluated were, respectively, 1,204-/+460 g and 30.5 -/+ 2.9 weeks.
      There was no statistical difference observed in newborns with and without
      pathologic gastroesophageal reflux according to clinical manifestations and
      monitoring conditions. Forty-eight newborns (56.4%) presented 17.6-/+9.1% of the
      whole examination time with a pH below 4. Of these patients, 31.1% presented
      birth-weight below 1,000 g. Duodenogastroesophagic was diagnosed in two cases. Of
      the studied premature with chronic lung disease, 66.7% presented pathologic
      reflux. CONCLUSION: Prolonged pH esophageal monitoring is helpful in the
      differential diagnosis of the unspecific and very frequent clinic manifestations
      in very low birth-weight infants.

PMID- 14685525
TI  - [Pain threshold and age in childhood and adolescence]
AB  - OBJECTIVE: The few investigations about pressure pain threshold in corporeal
      surface areas and children age showed no correlation between these parameters in
      all areas. In this research the existence of correlation between age and pressure
      pain threshold in seventeen areas of the corporeal surface of children was
      investigated. METHODS: A descriptive research was made with one hundred children
      from the Clinical Hospital of the Federal University of Minas Gerais. The
      selection of patients was made by directed search. There were forty five boys and
      fifty five girls with ages varying between 5.3 and 15.8 years old, and a mean (
      /+ standard deviation) of 9.6 (-/+ 2.7) years old. The seventeen corporeal areas
      studied were regions of the trapezium, deltoid and supraspinal muscles, nine
      areas of the abdomen and the median part of the tibias. The pressure of 0.5
      kg/cm(2)/s was made using a mechanical algometer. The pressure values that were
      recorded in the equipment when the children started to complain about the pain,
      by verbal communication, were considered as pressure pain thresholds. RESULTS:
      Positive correlations with significant statistic values were found between
      pressure pain threshold and age in every area investigated: trapezium, r = 0.36;
      deltoid, r = 0.34; supraspinal, r=0.42; hypochondrium, r=0.41; epigastrium,
      r=0.41; flank, r = 0.48; periumbilical, r = 0,40; iliac fossa, r = 0.49;
      hypogastrium, r = 0.45 and tibia, r = 0,29. CONCLUSIONS: Since correlations
      between age and pressure pain threshold were found in all areas studied, the age
      of a patient must be taken into consideration during clinical investigations and
      pain evaluations in children and adolescents. The younger the patient, the lower
      the pain thresholds.

PMID- 14685526
TI  - [Trends in hospital admissions for pediatric asthma in childrenduring a period of
      eighteen years]
AB  - OBJECTIVE: To study trends in hospital admissions for acute pediatric asthma in
      the Hospital da Santa Casa do Rio Grande during the period of 1979 to 1996.
      METHODS: This is a study of a series of cases. We reviewed all the discharge
      records of pediatric patients with diagnosis of acute asthma, pneumonia, and
      bronchiolitis within the period mentioned above. The main variable in this study
      was the percentage of admissions for acute asthma in relation to the total amount
      of hospital admissions. The percentages of admissions for bronchiolitis and
      pneumonia in relation to the total amount of hospital admissions were also
      calculated as reference values. RESULTS: There were 3,493 admissions for acute
      asthma in 3,122 patients during the studied period, with an average of 194
      admissions per year. The percentage of admissions for acute asthma to total
      hospital admissions increased from 5,5% to 14,7% between 1983/84 and 1991/92.
      Half of this increase occurred during the period 1987-1992 in which
      hospitalizations for bronchiolitis and pneumonia were stable. This percentage
      decreased from 14,7% to 10,6% in the period of 1991/92 - 1995/96. CONCLUSIONS:
      There was a significant increase in hospital admissions for acute pediatric
      asthma in the Hospital da Santa Casa do Rio Grande during the period of 1983 -
      1992. From then on, hospital admissions for asthma showed downward trends.

PMID- 14685527
TI  - [Blood pressure in school children and adolescents - The Belo Horizonte study]
AB  - OBJECTIVE: To investigate epidemiological aspects of blood pressure (BP) levels,
      and the prevalence of arterial hypertension in a representative sample of the
      whole elementary and high school population of the city of Belo Horizonte (state
      of Minas Gerais, southeastern Brazil). To describe the blood pressure levels
      found and the prevalence of BP levels above the 90th and 95th percentiles in the
      first and second measurements. To evaluate prevalence using four different
      normality references separately to assess the impact of choice of reference. To
      study the frequency at which the students blood pressure has been
      evaluated.METHODS: In an observational cross-sectional epidemiological study, we
      studied a sample of 1005 students, aged 6 to 18 year, randomized from an universe
      of 486,166 students from the 521 public and private elementary and high schools
      in the city. Each student was evaluated by means of a personal interview,
      anthropometric measurements, and two blood pressure measurements in a single
      visit and at a 10-minute interval.RESULTS: The systolic and diastolic blood
      pressure levels, by age and gender, were slightly lower than those described by
      the Task Force Report (1987) and by Rosner et al. (1993). The prevalence of BP
      levels (systolic or diastolic) over the 95th percentile were, according to the
      reference used: 8.7% - Task Force Report (1987); 5.5% - Rosner et al. (1993);
      6.5% - Update on the Task Force Report (1996); and 9.8% - the 95th percentile
      from our own study. In the second measurement these prevalence rates dropped to
      4.9%; 2.4%; 3.5% and 5.8%, respectively.CONCLUSIONS: We present a detailed
      description (mean values and standard deviations, and the 90th, 95th and 99th
      percentiles by age and gender) of the BP levels found in both measurements. Mean
      values and upper percentiles found in this study are very close to those found in
      the American references, which validates the current use of these references in
      Brazil. The prevalence of 9.0% of BP levels above the 90th percentile in two
      measurements made at random hints at the number of children who should be
      monitored for hypertension, and reinforces the importance of routine evaluation
      of blood pressure at every pediatric examination.

PMID- 14685528
TI  - [Effect of malnutrition and chronic use of nicotine during pregnancy on lung
      phospholipid concentration in neonate rats]
AB  - OBJECTIVE: The aim of the present study was to determine whether lung
      phospholipid concentration is affected in neonate rats "Wistar EPM-1" following a
      continuous 21-day gestational exposure to nicotine. METHODS: Eighty rats "Wistar
      EPM-1" were randomly divided in four control (diet free and water "ad libitum")
      groups (10 rats each): 1 - Control, 2 - Physiologic Solution (infused with 0.15ml
      of NaCl 0.9%), 3 - Nicotine 1 (infused with 900 micro g/kg/day of nicotine
      bitartrate 95%), and 4 - Nicotine 2 (infused with 2.700 micro g/kg/day of
      nicotine bitartrate 95%), and four undernourished (diet 13g/day and water ad
      libitum) groups (10 rats each), that received the same kind of treatment as the
      control groups. The infusion of nicotine was subcutaneous. The offspring were
      divided in eight groups according to their origin. RESULTS: A significant high
      lung phospholipid concentration was observed in the non-undernourished nicotized
      group which was injected with a high dose of nicotine. In the other groups, there
      was no alteration in that concentration. CONCLUSION: We conclude that gestational
      exposure to nicotine increases lung phospholipid concentration in neonate rats,
      and that the nutritional state also influences this lung phospholipid
      concentration.

PMID- 14685529
TI  - [The ineffectiveness of Technetium-99m-sestamibi for the pre-operative
      localization of parathyroid glands in neonatal primary hyperparathyroidism: case
      report]
AB  - OBJECTIVE: To present the case of a child with neonatal primary
      hyperparathyroidism submitted to preoperative image studies that couldn't
      localize the parathyroid glands. METHODS: Report of clinical and laboratory
      evaluation of neonatal primary hyperparathyroidism in a two-and-a-half-monthold
      child submitted to preoperative cervical ultrasonography and parathyroid
      scintigraphy with Technetium-99m-Sestamibi, and subtotal parathyroidectomy at the
      age of four-and-a -half months. RESULTS: The preoperative images suggested an
      erroneous diagnosis of parathyroid adenoma. After surgery and pos-operative
      histopathological exams, hyperplasia of parathyroid glands was confirmed. After
      two years and a half the child has normal parathyroid function. CONCLUSIONS: The
      cervical ultrasonography and the parathyroid scintigraphy with Technetium-99m
      Sestamibi were not useful for preoperative localization of hyperplasied
      parathyroid glands in the neonatal primary hyperparathyroidism in this case. The
      subtotal parathyroidectomy has been a successful method for the maintenance of
      normocalcemy in the patient.

PMID- 14685530
TI  - [Neurocutaneous melanosis]
AB  - OBJECTIVE: Describe the morbidity associated with a rare disease due to an
      embryological defect. METHODS: Retrospective revision of medical and necropsy
      reports. Bibliographic research using MEDLINE, LILACS and Index Medicus
      databases. RESULTS: 1 year-old male patient, admitted with generalized tonic
      clonic seizures, evolving to deep coma and death in a few hours. Necropsy showed
      diffuse leptomeningeal malignant melanoma in brain stem, cerebellum, spinal cord
      and temporal lobe associated with a giant melanocytic nevus and satellite
      lesions. CONCLUSIONS: Neurocutaneous melanosis is a rare congenital syndrome
      characterized by the presence of large and/or multiple melanocytic nevi and
      pigmented tumors of the leptomeninges. It has a poor prognosis as demonstrated by
      the present report. It's physiopathology is believed to be due to a migration
      defect of the cells arising from the primitive neural crest. In these cases, an
      early diagnosis may improve the survival time.

PMID- 14685531
TI  - [Munchausen syndrome by proxy - two case reports]
AB  - OBJECTIVE: To draw pediatrician's and healthcare worker's attention to the
      Munchausen syndrome by proxy, a serious kind of child abuse. PATIENTS AND
      METHODS: We report the clinical history and the evolution of two patients, based
      on a review of these patient's files in the Children's Rights Committee of the
      Hospital da Crianca Santo Antonio, for further discussion. The first case reports
      a 5- year old child that presented difficult-controlling seizures; this case had
      an excellent prognosis after being examined by several specialists and later on
      by the Children's Right Committee. The second case reported is a 5-month old
      infant who presented apnea crisis accompanied by cyanosis and seizures. COMMENT:
      Munchausen syndrome by proxy is a relatively rare clinical entity, that can be
      difficult to be diagnosed, leading to unnecessary and potentially harmful
      diagnostic procedures to the child.

PMID- 14685533
TI  - [Sickle cell disease: a serious and unknown problem of public health in Brazil]

PMID- 14685534
TI  - [Immunologic abnormalities in HIV-infected children]

PMID- 14685532
TI  - [Epidermal nevus syndrome - a case report]
AB  - OBJECTIVES: To present the case of a patient with an epidermal nevus since birth
      and its relationship to neurologic signs and symptoms, emphasizing the importance
      of cutaneous manifestations as early markers of syndromes involving the Central
      Nervous System. METHODS: Clinical, radiological and histopathological data were
      analyzed. RESULTS: We report the case of a boy with an erythematous lesion on the
      neck and cheek since birth. At 9 months the lesion was velvety and slightly brown
      in color, with associated hemihypertrophy of the face. After 3 months he was
      hospitalized for having seizures. Computerized tomography of the brain disclosed
      hemimegalencephaly ipsilateral to the cutaneous lesions. DISCUSSION: The
      cutaneous findings can be an indicator of neurologic disease since both tissues
      have the same embryological origin: the neural crest. Thus, the Pediatrician must
      recognize these cutaneous signs which appear early in life and characterize some
      of the Neurocutaneous Syndromes so that a proper diagnosis and follow-up can be
      made.

PMID- 14685535
TI  - [Assessing and treating pain in the newborn]
AB  - OBJECTIVES: To update information about available neonatal pain assessment and
      pain relief methods.METHOD: Medical literature review of the past 10 years,
      including textbooks, general reviews, systematic reviews, prospective, randomized
      controlled studies, retrospective works and case studies. Literature was reviewed
      based on the author clinical and scientific experience regarding pain evaluation
      and treatment.RESULTS: Lack of verbal expression of pain is one of the major
      impediments to adequate pain relief in the neonatal period. Nowadays, several
      valid pain assessment tools are available, including the analysis of the neonate
      facial features and multidimensional tools, as NIPS, CRIES, and PIPP. Non
      pharmacological pain relief can be achieved by non-nutritive suction and suction
      of dextrose water. Neonatal analgesia, in general, includes de the use of
      paracetamol, opioids and local anesthetics. Opioids remain the main resource for
      acute pain treatment in the neonatal intensive care unit. Sedatives are important
      agents to decrease patient activity and restlessness, but they do not relieve
      pain.CONCLUSION: Based on medical, ethical, and humanitarian grounds, neonatal
      pain should be considered and treated.

PMID- 14685536
TI  - [Nutritional approach in pregnant and nursing adolescents: basic strategy to
      prevent risks]
AB  - OBJECTIVE: To present the different factors that can interfere in the neonatal
      evolution and results, as well as the approach strategic nutritional aspects in
      health promotion and attention of pregnant nursing adolescents. METHOD: National
      and international literature provided with subsidies to discuss and summarize
      practical and relevant aspects for the clinical assistance of pregnant and
      nursing adolescents, especially the lower age group. RESULTS: The approach to
      pregnant adolescents requires evaluation of parameters of clinical, nutritional,
      and psychosocial risk. Among the very young adolescents, in addition to those
      parameters, their gynecological age and physical growth stage are also relevant.
      The nutritional evaluation and the dietary orientation of the pregnant and
      nursing adolescents constitute support steps in health promotion and attention,
      preventing risks such as malnutrition, anemia, vitamin deficiency, in addition to
      low intrauterine growth, low birth weight and postnatal undernourishment.
      CONCLUSION: The complexity of the factors interfering in the course of precocious
      pregnancy requires deep knowledge of the problem by the health staff in order to
      be able to effectively to intervene in more critical and prior aspects of the
      health support for this risk group.

PMID- 14685537
TI  - [Hemoglobin "S" positive newborn detected by cord blood and its characteristics]
AB  - OBJECTIVE: To evaluate the prevalence of hemoglobin "S" (Hb "S") in babies born
      at the Instituto Materno Infantil de Pernambuco (IMIP) and its occurrence
      according to sex, birth weight and Apgar score. METHODS: We carried out a cross
      sectional descriptive study of all babies born in the IMIP from October 1996 to
      March 1997. We used alkaline electrophoresis to analyze cord blood samples
      (1,988). Data for other variables were collected from medical reports. EPI-Info
      6.0 was used to analyze the data.RESULTS: We found 105 (5.3%) newborns with Hb
      "S": 102 (5.1%.) as sickle cell trait (Hb "FAS"), and 3 (0.2%) as sickle cell
      disease (Hb "SC"). No cases of homozygosis were found. Newborns with and without
      Hb "S" did not differ in relation to sex, birth weight and Apgar score.
      CONCLUSIONS: We suggest the implementation of neonatal screening for
      hemoglobinopathies for all the newborns in Recife, Brazil, with further follow up
      focusing on genetic counseling for suspected and positive cases.

PMID- 14685538
TI  - [Immunological evaluation of 60 children with AIDS]
AB  - OBJECTIVE: The immunologic defects that occur in children with HIV infection are
      important tests to both diagnosis and therapeutic response. The objective of this
      study was to verify the immunologic abnormalities in 60 children with AIDS, in
      Florianopolis, Santa Catarina State, Brazil. METHODS: Serum immunoglobulin levels
      were determined by nephelometry and compared to a normal pattern for Brazilian
      children. The lymphocyte T helper (CD4+) and the lymphocyte T suppressor (CD8+)
      count and percentage, and the ratio between them, determined by commercial flow
      cytometry, were compared to a pattern for healthy children of HIV-positive
      mothers. RESULTS: The mean serum IgG levels was higher in the children with AIDS
      (p<0.005). The mean serum IgM levels was higher in the children with AIDS in the
      age group between 13 and 108 months (p<0.005). The CD4+ lymphocytes count was
      below the inferior limit of the 95% confidence interval of the median reference
      values to each group of age in 50 (84.7%) of the 59 determinations. The CD4+
      lymphocytes percentage was much lower than the percentages of reference. The
      graph curve of the medians of the ratio between lymphocytes CD4+ and CD8+ to each
      group of age was below the fifth percentile of the graph curve of the medians of
      reference. CONCLUSIONS: The hypergamaglobulinemia and the lymphocyte T CD4+ count
      and percentage are sensitive indicators of HIV infection, observed in the present
      study. Immunologic evaluation of the HIV-positive children is recommended,
      including those younger than 18 months of age.

PMID- 14685539
TI  - [A descriptive study of burn injuries in children and adolescents]
AB  - OBJECTIVE: To investigate the frequency of different kinds of burns, associated
      factors, major complications and their relations to other variables. METHODS:
      Descriptive study performed at Hospital Joao XXIII from January to December of
      1992 with five hundred and thirtyseven children and adolescents. RESULTS: The age
      distribution was as follows: 408 patients were children (76%) and 129 were
      teenagers (24%). Most of the accidents, 398 cases (74%) happened at home, 235 of
      which (59%) in the kitchen. 80 patients were interned. They had the highest
      relative frequency of accidents outside home (p<0.05). Of these interned
      patients, 7 (9.0%) developed septicemia. The flame was the predominant agent
      within the group of inpatients (p<0.01) and was responsible for the highest
      extension of burning (p<0.05). Teenagers had the largest body burned surface
      compared to children (p<0.01). Local treatment with pomade or home made medicine
      was observed in 290 cases (54%); local wash with water only in 32 (6.0%).
      Dehydration was the most frequent complication and occurred in 28 (5,0%)
      patients. The average amount of internment was 30-/+33 days. CONCLUSIONS: Most of
      burning were consequence of domestic accidents, especially in youngers than 7
      years old; hot liquids are the most frequent agents and kitchen the most frequent
      place. Flame, which determined the largest and deepest lesions, was the first
      cause of burns in teenagers and the second in children. Dehydration is the most
      frequent complication in the earlier phases and septicemia in the others.

PMID- 14685540
TI  - [Plasmodium vivax malaria in children and adolescents - epidemiological, clinical
      and laboratory features]
AB  - OBJECTIVE: Evaluation of epidemiological, clinical and laboratory features of
      Plasmodium vivax malaria in children and adolescents. METHODS: This study was
      carried out in the Malaria Program of the Evandro Chagas Institute (Belem, Para),
      from January 1995 to November 1996. 100 children and adolescents with the
      diagnosis of P. vivax malaria (thick blood film) were randomly enrolled. A
      protocol was created to assess epidemiological, clinical and laboratory
      parameters of this pathology. RESULTS: Malaria occurred in both sexes, and had a
      prevailing incidence among adolescents (37%). Most of the children and
      adolescents (92%) had been infected in the State of Para. Autochthonous cases in
      the metropolitan area of Belem accounted for 34 % of the sample. Primary
      infection was seen in 80% of the patients. Fever was the major onset clinical
      symptom (88%). A history of typical febrile paroxysm was recorded in only 25% of
      the casuistic. In the first day of treatment (D0) fever (97%), chills (91%),
      pallor (85%), splenomegaly (46%) and hepatomegaly (29%) were some of the clinical
      features observed. Pallor (clinical signal) was found to be significantly
      (p=0.0004) associated with anemia (hemoglobin rate). There was a high significant
      negative correlation (p=0.0001) between delay of diagnosis (mean 12,5 days) and
      hemoglobin values. Regarding parasitological examination, just children and
      adolescents with positive results to hookworms were significantly (p=0.0133,
      p=0.0075) more anemic than those who had a positive parasitological examination
      to other helminths and/or protozoa species. CONCLUSIONS: Malaria affected
      children and adolescents from both sexes. An emphasis on epidemiological and
      clinical data is an important tool to the precocious diagnosis of the disease.
      Delay on diagnosis made anemia worse.

PMID- 14685541
TI  - [Clinical manifestations in term newborn infants with different degrees of
      acidemia in umbilical cord blood]
AB  - OBJECTIVE: To verify if Apgar score plus umbilical cord pH are adequate to
      predict which newborn infant will develop multiorgan system disfunction. METHODS:
      A study including all term newborn infants with Apgar scores in the first and
      fifth minutes of life < 7 and umbilical cord blood pH < 7.20 born in Hospital de
      Clinicas de Porto Alegre from March 1995 through March 1998 was performed. Venous
      umbilical cord blood was collected for blood gas analysis. Newborn infants were
      divided in two groups: Group A with pH < 7.0, and Group B with pH >/= 7.0 and <
      7.20. Patients were evaluated for the presence of pulmonary hypertension, renal
      failure, inappropriate secretion of antidiuretic hormone, ischemic cardiopathy,
      early seizures, neurologic injury at hospital discharge and death. RESULTS:
      Twenty five newborn infants were included in the study.Twelve formed Group A, and
      13, Group B. There were no differences between both groups in respect to mode of
      delivery, gender, color and birth weight. Group B had a lower gestational age
      than Group A. There were significant differences between both groups in mean cord
      blood pH, pCO(2) and BE (p<0.05). There was a positive association between
      umbilical cord blood pH and Apgar score. Higher occurrence of neurologic injury
      at hospital discharge in Group A was the only statistically significant clinical
      manifestation (p<0.05). CONCLUSION: Apgar score and umbilical cord pH are not
      adequate criteria to predict multiorgan system dysfunction.

PMID- 14685542
TI  - [Hemicrania continua]
AB  - OBJECTIVE: To report a case of Hemicrania Continua in a female aged 17, who
      presented this kind of headache for 9 years without diagnosis. Although this may
      be a relatively rare primary headache, the immediate response to clinical
      treatment with indomethacin justifies this entity be better known. METHODS: Case
      report of a female adolescent who had presented Hemicrania Continua for many
      years, without diagnosis and adequate treatment. Review of the relevant medical
      literature by means of Medline. RESULTS: Treatment with low doses of indomethacin
      caused complete cessation of the headache. CONCLUSION: Hemicrania Continua must
      be considered as a diagnostic possibility for patients who present continuous
      unilateral headache, without abnormalities in the clinical, neurologic and
      laboratorial examination, irrespective of the age the headache starts. This is
      the youngest patient reported to have Hemicrania continua and it was brought to
      discussion by a medical student, aware of this possible diagnosis.

PMID- 14685543
TI  - [Relapse on Kawasaki disease]
AB  - OBJECTIVES: to draw the pediatrician's attention to the characteristics, the
      diagnostic criteria and the possibility of relapse of the acute phase of the
      Kawasaki disease with its possible complications. METHOD: case report of a
      patient registered at Hospital Universitario de Brasilia under medical record
      number 400682 and review of the literature. RESULTS: Case report of a boy who
      relapsed the clinical aspects of the disease, after disappearance of signs and
      symptoms of the acute phase, and who complicated with aneurysm of the left
      coronary artery. CONCLUSION: the diagnosis of Kawasaki Disease is based on
      clinical findings. The pediatrician should be always alert to the diagnostic
      criteria since this is a disorder that may lead to heart complications following
      the acute phase or after its recurrence. These cardiac complications may lead to
      death in 2% of the patients.

PMID- 14685544
TI  - [Intestinal colonization by multidrug resistant enterobacteria: living with the
      enemy]

PMID- 14685545
TI  - [High blood pressure in children and adolescents: determinant factors]
AB  - OBJECTIVE: To review the state of prevalence of hypertension in childhood and the
      importance of its possible determinants. METHODS: Analysis of the literature
      concerned with eleven possible determinant factors - experimental design,
      internal and external validity. RESULTS AND CONCLUSIONS: Central body fat pattern
      seems to be a risk factor, while heart rate and tracking would be true markers of
      future hypertension. Social class, biological maturation, race, sodium intake and
      genetic factors have not yet been validated through unbiased studies.

PMID- 14685546
TI  - [Newborn intestinal colonization by multidrug resistant enterobacteria in a
      neonatal unit]
AB  - OBJECTIVE: To evaluate the occurrence of intestinal colonization in newborns by
      multidrug-resistant enterobacteria strains (MDRES) during hospital stay after
      birth. We used selective media in an attempt to determine the relationship
      between isolation of these strains and some of the presumed colonization risk
      factors. METHOD: A sequencial inclusion study of 30 newborns was carried out in
      the neonatal unit of the HUPE, State University Hospital, a general 600-bed
      tertiary care hospital. We obtained clinical and epidemiological information from
      medical records and collected a fecal sample from each newborn, which was plated
      in gentamicin (8mg/ml) medium and potassium tellurite (25mg/ml) medium. The
      isolated strains were biochemically identified and also submitted to tests of
      antimicrobial susceptibility. Nine MDRES were submitted to an assay for plasmid
      conjugational transfer. RESULTS: We isolated 56 distinct MDRES from 14 among 30
      newborns (46.7%). Klebsiella pneumoniae was the most common bacterial species
      (38/56 (68%). We found statistical association between individual MDRES isolation
      and presence of 3 or 4 of the following colonization risk factors considered:
      antimicrobial use, low weight (<2.500g), more than 6 days of hospitalization and
      artificial milk feeding (p< 0.02). We could detect plasmid resistance transfer by
      bacterial conjugation for 8 among 9 MDRES. CONCLUSION: The seletive cultura media
      were useful to detect the high frequence of newborns colonized by MDRES in
      association with well established infection risk factors. We emphasize the
      importance of reinforcing control rules aiming at preventing intestinal
      colonization viewed as a risk of nosocomial infection.

PMID- 14685547
TI  - [Accuracy of the oscillometric method to measure blood pressure in children]
AB  - OBJECTIVE: The aim of this study is to analyze the substitution of the standard
      auscultatory method by the oscillometric blood pressure monitor, independently of
      the validity of the intraarterial blood pressure measurement. The accuracy of the
      automatic oscillometric monitor was compared to the auscultatory mercury
      manometer blood pressure measurement in apparently healthy school age children.
      METHODS: A device able to perform 3 simultaneous readings are used: one reading
      by the monitor and the others by two "blind" observers. We studied 72 school age
      children with the following characteristics: mean age 9.5 (6.1-16.1) and 39 males
      (54.2%). RESULTS: The difference for the systolic and diastolic blood pressure
      obtained by the monitor was in average + 6.2 mmHg and + 10.0 mmHg, respectively,
      when compared to the observer's readings. There was neither a good correlation
      nor a good agreement between the two observers and the monitor in the blood
      pressure determination. CONCLUSIONS: We concluded that the substitution of the
      standard auscultatory method for the non-invasive oscillometric method to measure
      blood pressure in school age children can not be generally recommended.

PMID- 14685548
TI  - [Acute diarrhea in children less than 3 years of age: Enteropathogens isolated in
      patient's stools, compared with a control group]
AB  - OBJECTIVES: To observe the occurrence of different etiological agents of acute
      diarrhea (AD) in stool specimens of patients and children in a control group.
      MATERIAL AND METHODS: 100 children less than three years of age with AD were
      studied as well as 100 controls, between November 1993 and May 1994. Stool
      specimens were collected in both groups and the following enteropathogens were
      searched for: Rotavirus, Escherichia coli (EPEC, ETEC, EIEC, EHEC), Salmonella
      sp, Shigella sp, Campylobacter jejuni, Campylobacter coli, Yersinia
      enterocolitica, Cryptosporidium sp, Giardia lamblia, Entamoeba histolytica.
      Statistical analysis using the exact Fisher test (at significance level p<0,05)
      was done. The mean age was 12,5 months, with more cases in patients less than 6
      months (35%). Children were seen at the emergency section on an average fifth day
      after the start of the diarrhea. Most came from homes with basical sanitary
      conditions. Watery diarrhea was more frequent than bloody diarrhea with mucus, at
      a proportion of 4:1. RESULTS: Rotavirus was the most frequent agent: 21% in the
      AD group and 3% in the control group (p= 0,0001). Shigella sp was isolated in 7%
      of the AD group and none of the control group (p= 0,0140). EPEC was detected in
      13% of AD cases and 7% in the control group (p= 0,2381) but the classical
      subgroups O55, O111, O119 were only isolated from the patients with AD. The other
      enteropathogens were infrequently detected or in equal proportion in both groups.
      Rotavirus and EPEC were the more frequently isolated agents in watery diarrhea,
      while Shigella sp was the predominant agent found in bloody stools with mucus.
      CONCLUSIONS: Rotavirus was the most common causative agent in AD. The detection
      of Rotavirus and Shigella sp nearly exclusively in patients with AD confirms the
      high patogenicity of these etiological agents when compared to the others.
      Escherichia coli (EPEC) diagnosed by polyvalent sera does not confirm its
      respective diarrheogenic property due to isolation in the same proportion among
      patients with AD and controls. Monovalent antisera made possible the detection of
      classical subgroups of EPEC O111, O119, O55 isolated only from AD patients,
      confirming the already known high patogenicity of these strains.

PMID- 14685549
TI  - [Retinol-binding protein urinary levels in a pediatric population: evolution
      according to age]
AB  - OBJECTIVE: The kidney of the child, mainly the newborn, is specially susceptible
      to ischemic and/or toxic injuries, which can affect the renal tubular function.
      Therefore, reliable and precocious markers of tubular dysfunction would be useful
      in Pediatrics. The urinary levels of retinol binding-protein (RBPu) has been used
      in this way. Our goal was to evaluate the RBPu behavior in childhood to establish
      a reference interval and verify possible differences according to the age.
      METHODS: We studied healthy children aged 1 month to 8 years and healthy term and
      preterm babies; in the last group we only included babies without hemodynamic
      repercussion. We collected isolated urine samples once for children above 1 month
      and periodically for those below this age. In this urine, besides the dipsticks
      test (Combur 9(R), Boehringer), RBPu and creatinine were measured. RESULTS: We
      observed that the RBPu levels in childhood do not have a normal distribution;
      after logarithm data transformation we were able to establish an interval of
      reference for children above one month of age: 3 to 269 micro g/L, mean of 27
      micro g/ L. In newborns, we found a large variation of RBPu excretion. However,
      we noticed that the excretion decreases significantly, reaching the healthy adult
      levels at the end of the 1st month, for term as well as for preterm newborns.
      CONCLUSIONS: We suggest that RBPu can be used as a marker of proximal tubular
      dysfunction, since we could establish an interval of reference, and it can be
      repeated whenever necessary in the follow-up of this kind of injury, because it
      is not an invasive exam. Moreover, this study contributes to the knowledge of the
      tubular function development for showing that at the end of the 1st month of life
      the newborn's kidney is able to reabsorb RBPu as the healthy adult kidney is.

PMID- 14685550
TI  - [Assessment of the Breastfeeding Counselling Course WHO/UNICEF]
AB  - OBJECTIVES: To assess the implementation and the impact of the Breastfeeding
      Counselling Course WHO/UNICEF on knowledge and skills of health workers.
      METHODOLOGY: The implementation of the course was assessed by participant
      observation; the impact on participants was assessed with an experimental
      controlled study where 20 health workers were randomly allocated as course
      participants (Exposed Group-EG) and 40 as non participants (Control Group -CG).
      Impact on knowledge was verified with pre and post evaluations, with multiple
      choice questions; clinical and counselling skills were assessed through pre and
      post tests, observing participants in clinical consults with mother and baby
      pairs in rooming-in before and after the course. Kruskal-Wallis test of variance
      of means was used in analysis. RESULTS: In the post test of knowledge, the mean
      of the EG was 8.35 and that of the CG was 5.54 (p=0,0000). In clinical and
      counselling skills, the means of the EG were higher when compared with the CG in
      all items observed (p < 0,05). Some difficulties were found in breastfeeding
      history and in breastfeeding observation. Counselling skills were the most
      incorporated aspects. CONCLUSION: The course may be implemented as proposed;
      participants acquired counselling skills, but clinical management should be
      reinforced; participants shoud have continued support to put what they learned in
      practice.

PMID- 14685551
TI  - [Congenital syphilis: incidence among newborns]
AB  - OBJECTIVE: To determine the incidence of congenital syphilis among newborns at
      the maternity of a public hospital. METHODS: The study was conducted at the
      maternity of Fundacao Santa Casa de Misericordia do Para, from May to September
      1996; 361 mothers were interviewed, and physical examination was performed in
      their newborns. Serum samples from both, mothers and neonates, were tested using
      three methods: VDRL, FTA - Abs, ELISA IgM. The diagnosis of congenital syphilis
      was established according to the criteria defined by Ministerio da Saude in 1993.
      RESULTS: The rate of congenital syphilis was of 9.1% (33); in 14 cases, there
      were one or more signs of the disease: prematurity, hepatomegaly, stillbirth,
      splenomegaly, perinatal death, abdominal distention, nasal stuffiness, jaundice,
      newborn small for gestational age. The majority of the infected mothers belonged
      to the age group of 20-35 years (81.8%); 60.6% were married; 63.6% received
      prenatal care; 48.5% reported previous spontaneous abortion, and 12.1% previous
      stillbirth. The rate of bisexuality among fathers was of 9.1%. CONCLUSION: The
      syphilis control measures and the prenatal care, have not been sufficient to
      prevent the high rate of the disease.

PMID- 14685552
TI  - [Perinatal cytomegalovirus infection: commonly occurring but rarely diagnosed]
AB  - OBJECTIVE: To determine the incidence rate of perinatal cytomegalovirus (CMV)
      infection and to describe the clinical presentation of this infection in non
      transfused term infants attended at a general hospital, in Ribeirao Preto, SP,
      Brazil. POPULATION AND METHODS: Thirty four infants free of CMV infection at
      birth were followed up during the first 4 months of life. Diagnosis of perinatal
      CMV infection was established by isolating the virus in tissue culture or by
      polymerase chain reaction DNA amplification (PCR) in urine samples. RESULTS: A
      38.2% (13/34) incidence rate of perinatal CMV infection was detected, and only 3
      of the infected infants were symptomatic (respiratory tract symptoms in one
      infant and splenomegaly in two). CONCLUSIONS: The results indicate a high
      incidence rate of perinatal CMV infection in the studied infants. Clinical
      symptoms were present in 23% of these patients, stimulating the investigation of
      this agent as a cause of pneumonitis and splenomegaly.

PMID- 14685553
TI  - [Ornithine transcarbamylase deficiency: neonatal diagnostic]
AB  - OBJECTIVE: To drive pediatrician's attention to a urea cycle enzyme deficiency.
      The prognosis is directly related to the early diagnosis and treatment. METHODS:
      We describe a newborn patient who present lethargy, vomitus and seizures 48 hours
      afther birth. We investigated this patient and the diagnosis of ornithine
      transcarbamylase deficiency was made. Treatment was started immediately. RESULTS:
      We followed the patient until he was 1 year old, when he had liver transplant
      with a good outcome of the disease. CONCLUSION: The ornithine transcarbamylase
      deficiency is a rare and very serious disease. Any newborn whose evolution is
      similar to that of a septic patient without any infection must be investigated
      for this disease. The prognosis is directly related to the early diagnosis and
      treatment.

PMID- 14685554
TI  - [Late-presenting congenital diaphragmatic hernia: a possible cause of sudden
      respiratory distress in children]
AB  - OBJECTIVE: To emphasize that congenital defects of the diaphragm should be
      considered in the differential diagnosis of sudden onset of respiratory distress
      in children. MATHOD: Two illustrative cases of children (aged 2 years) with late
      presenting congenital diaphragmatic hernia who developed sudden respiratory
      distress and were managed at the University Hospital of Santa Maria are reported.
      The medical literature was reviewed to identify cases reports and other articles
      related to late presenting congenital diaphragmatic hernia. A computerized search
      was performed using the MEDLINE data base to identify papers published within the
      last 25 years. RESULTS: In both cases the initial clinical examination and plain
      chest X-rays were misinterpreted as another pleuropulmonary disease like
      pneumothorax/pneumatoceles. One of the children underwent to emergency chest tube
      placement without clinical improvement. The absence of respiratory symptoms that
      could justify this kind of pathology motivated a more careful investigation,
      involving fiberoptical endoscopy and intestinal seriography. This subsequent
      investigation revealed that the cause was late-presenting congenital
      diaphragmatic hernia. CONCLUSION: Although many congenital diaphragmatic hernias
      that present late have a history of chronic respiratory symptoms, some of them
      present with acute symptoms. A higher degree of attention is required to avoid
      confusion with other intrathoracic conditions, such as pneumatoceles and
      pneumothorax, if an incorrect diagnosis is to be avoided. Misinterpretation of
      the radiographs is likely if the possibility of a congenital diaphragmatic hernia
      is not considered, and may result in increased morbidity. Gastric atony may occur
      in the early postoperative period.

PMID- 14685556
TI  - [Interleukines and neonatal sepsis]

PMID- 14685555
TI  - [Cytomegalovirus (CMV).].

PMID- 14685557
TI  - [Rooming-in history]
AB  - OBJECTIVE: To review the rooming-in facility for mother and child and the
      transformations in the perinatal care. METHOD: This is a bibliographic review
      with a content analysis from a historical point of view. OUTCOME: Until the
      beginning of this century, labor and birth were strictly a domestic event under
      the responsibility of women. When the hospitals began to offer new techniques
      they became the place of choice to treat all kinds of patients. This new way of
      treatment confined patients in hospitals away from their relatives and friends.
      Even newborn babies were to be left alone in nurseries away from their mothers,
      in order to be protected from any kind of infection. In the late 40s, researchers
      connected the mother-child separation at birth to some disadjustments in family
      relations and this led the way to a new research field. One of the innovations
      was a rooming-in facility for mother and child. This was first used as a trial
      whose intention was to re-empower the mother with her baby care. As a trial it
      ended and was only reborn in the 70s sponsored by WHO and UNICEF. CONCLUSIONS:
      Mother-child separation raises maternal insecurity, decreases breast feeding and
      deprives the baby from his mother's love and care. It has been already shown that
      children who are separated from their mothers at birth are more likely to be
      abandoned, hurt or abused. Thus it should be advisable to enroll health
      professionals in promoting mental and psychological health of mothers, babies and
      their families.

PMID- 14685558
TI  - [Controversial drugs in otorhinolaryngology]
AB  - OBJECTIVES: To present a review on the most important groups of drugs used to
      treat otorhinolaryngological disorders. METHOD: Review of the literature about
      treatment of pediatric upper respiratory infections and allergy, using MEDLINE
      and LILACS data. RESULTS AND COMMENTS: Pediatric otorhinolaryngological disorders
      are extremely frequent and most of the time acute. They are one of the major
      reasons for pediatric visits. The therapeutical management of these conditions in
      many cases accounts for an over use of drugs, specially antibiotics, antipyretic
      and drugs of doubtful value, such as decongestants and expectorants. Judicious
      use, correct indication, and side effects of these drugs must be better known by
      physicians who deal with the child's health.

PMID- 14685559
TI  - [Prevalence and clinical aspects of congenital cytomegalovirus infection]
AB  - OBJECTIVES: The objectives of the present study were to determine the prevalence
      of congenital CMV infection, as well as to evaluate the importance of this agent
      as cause of congenital disease, and to describe the clinical manifestations in
      children attended at a General Hospital in Ribeirao Preto, SP, Brazil. POPULATION
      AND METHODS: A first group including 189 newborns and their mothers was evaluated
      for the prevalence of the congenital CMV infection. A second group including 130
      newborns and 74 infants who presented clinical manifestations of congenital
      disease were also investigated to evaluate the importance of the CMV as a cause
      of this disease and to describe the clinical findings. Diagnosis of congenital
      CMV infection was established by detecting the virus using viral isolation in
      tissue culture, polymerase chain reaction DNA amplification in urine samples and
      detection of specific anti-CMV IgM and IgG by immunofluorescence indirect test.
      RESULTS: The prevalence of congenital CMV infection was 2.6% and the prevalence
      of CMV antibodies in mothers was 95%. In the first group, none of the 5
      congenitally infected presented clinical apparent disease at birth, although one
      of them had intracranial calcifications. In the second group, CMV was recognized
      as a causative of congenital disease in 12 children (5.9%). Of these, 10(83%)
      were identified after the neonatal period. The clinical findings included
      hepatosplenomegaly (75%), jaundice with direct hyperbilirubinemia (42%),
      neurologic disease consisting of microcephaly and intracranial calcifications in
      42% of these children. CONCLUSIONS: The prevalence of congenital CMV infection
      was similar to that reported in other studies about highly immune populations.
      Infants with asymptomatic congenital CMV infection may have diseases of the
      central nervous system that are not clinically evident at birth, such as punctate
      calcifications. CMV infected patients who are symptomatic at birth have a
      multisystem disease, and the differential diagnosis of any newborn with clinical
      abnormalities including involvement of the hepatobiliary, hematopoietic and
      central nervous systems should include congenital CMV infection. CMV was an
      important agent of these abnormalities, and the majority of symptomatic patients
      were identified after the neonatal period, making the diagnosis more difficult.

PMID- 14685560
TI  - [Plasmatic levels of interleukin-1beta and interleukin-6 in newborn infants with
      fever]
AB  - OBJECTIVE: To study plasma levels of IL-1beta and IL-6 in order to distinguish
      the presence of bacterial infection in newborn infants with fever. METHODS: A
      cohort of 117 newborn infants with postnatal age equal to or less than 5 days,
      with no previous use of antibiotic therapy, and with clinical suspicion of
      bacterial infection was studied from July 1995 through August 1996. Those with
      definite criteria for sepsis were considered infected. Fever was defined as
      axillar temperature > 37.5 degrees C in three independent measurements. The
      patients were classified in four different groups: Group 1: infected with fever;
      Group 2: infected without fever; Group 3: not infected with fever; Group 4: not
      infected without fever. Complete blood count, platelet count, blood or other
      fluid cultures, and plasmatic levels of IL-1beta and IL-6 were collected before
      the beginning of antibiotic therapy. RESULTS: Of the 117 newborn infants studied
      were 66 infected and 51 not infected. Fever was present in 45 (38.46%). The
      median values of IL-1beta and IL-6 were significantly higher in newborn infants
      with fever than in those with no fever. There were significant differences
      between groups 1 and 2, 1 and 4, and 2 and 3 for IL-1beta. There were no
      significant differences between groups 2 and 4, and 1 and 3 for IL-1beta. Eight
      (72%) newborn infants with no infection and no fever had environment heating, and
      3 had dehydration. There were no differences in median IL-6 levels between groups
      1 and 2, and 3 and 4. There were significant differences in the median IL-6
      levels between groups 1 and 3, and 1 and 4. CONCLUSIONS: IL- 6 is a marker of
      early neonatal sepsis. IL-1beta is related to neonatal fever response
      independently of the presence of bacterial infection.

PMID- 14685561
TI  - [Factors that can interfere in the result of blood culture in pediatric intensive
      care unit]
AB  - OBJECTIVE: To analyze factors that can interfere with the results of blood
      culture in a pediatric population, as there are few reports of standardization of
      blood culture in Pediatrics. METHODS: During three months 100 blood samples,
      collected at the Pediatric Intensive Care Unit of the "Hospital das Clinicas" of
      the Medical School of the Campinas State University (UNICAMP) were analyzed with
      respect to site and manner of collecting, age of the patients, clinical
      diagnosis, type of antiseptic substance used and blood volume withdrawn for
      sample. RESULTS: Two samples were sufficient to diagnose bacteremia. The
      positivity of the samples were related to the age of the patients. The rate of
      contamination related to the total number of samples was of 5%. All the false
      positive samples were collected from children less than one year of age. The
      blood culture diagnosed bacteremia by multiresistant agents even in patients
      using antibiotics. CONCLUSIONS: The contamination of the samples (false
      positives) was related with the age of the children, probably with the difficulty
      to obtain the blood. The interference of the antibiotics were demonstrated,
      specially in Pediatric Intensive Care Unit. Blood culture was useful to identify
      multiresistant agents in children receiving broad spectrum antibiotics. Because
      of the importance of blood culture and the knowledge of factors that can
      interfere with the results, one should be critical regarding indication and way
      of collecting the exam in order to avoid iatrogenic problems to the patients.

PMID- 14685562
TI  - [Sepsis in childhood: epidemiological profile and microbiologic diagnosis]
AB  - OBJECTIVE: To establish an etiological and epidemiological profile of sepsis
      among children that were hospitalized in the Hospital Infantil Albert Sabin -
      HIAS (a reference public hospital for all pediatric diseases in the state of
      Ceara), since this disease has been of high prevalence in this hospital with
      considerable mortality. METHODS: All children admitted in the hospital from
      January 1993 to June 1994, who presented sepsis or developed nosocomial sepsis
      and presented positive blood cultures were studied prospectively. The
      epidemiologic study was conducted by gathering information in questionnaire form
      about the following factors: sex, age, reference area, nutritional status,
      complaints at admission, sepsis origin (nosocomial or not), and outcome for each
      case. Microbiologic analysis were formed by means of blood culture, concomitant
      with sensitivity tests of the isolated bacteria to the most commonly used
      antibiotics. All samples were processed at the Laboratory of Microbiology of the
      Health's Science Center of the Federal University in Ceara. RESULTS: 205 children
      were studied of which 17 presented two septic episodes, making a total of 222
      episodes in the period. 56.1% of them were male, 81.4% were less than one-year
      old, 71.1% were malnourished children and 60.5% came from the countryside of the
      Ceara State. At the moment of their admission, two-thirds of the children
      presented gastrointestinal problems (diarrhea) or respiratory complaints, whereas
      47.7% of the episodes of sepsis were acquired in hospital. The mortality rate was
      56.1%. Blood culture test showed a predominance of the following bacteria:
      Staphylococcus aureus (24.8%), Klebsiella pneumoniae (22.6%), Pseudomonas
      aeruginosa (15.2%), Enterobacter sp (11.2%), Escherichia coli (7%), and others
      (19.2%). CONCLUSIONS: The epidemiological profile of the population in this study
      was the following: these children were less than one-year old, the majority of
      them were malnourished and when they were hospitalized, presented with symptoms
      of diarrhea or respiratory disease. 40% of them had a disease or situation that
      favored the development of sepsis. The predominant bacterias were Staphylococcus
      aureus and Klebsiella pneumoniae.

PMID- 14685563
TI  - [Normal neonatal cerebral ultrasonography in preterm infants - Is it possible to
      calm down the parents?]
AB  - OBJECTIVE: To verify the predictive values of neonatal cerebral ultrasonography
      for motor and cognitive development of very low birth weight preterm babies after
      twelve months correct age. METHODS: The population studied was a cohort of
      preterm babies with birth weight less than 1,500g, who had been admitted in the
      Neonatal Intensive Care Unit of Instituto Fernandes Figueira, and were followed
      to 12-30 months corrected age for prematurity. A cerebral ultrasonography was
      performed before discharge. The results were classified as normal and abnormal
      (parenchymal hemorrhage, porencephaly, periventricular leucomalacia, ventricular
      dilatation). The babies were followed in the Follow-up Clinic and between 12-30
      months correct age they underwent a neurological assessment with observation of
      the acquisition of motor milestones and submitted to Bayley Scales of
      Development. RESULTS: We studied 83 babies. Cerebral ultrasonography was normal
      in 68 babies (81.9%) and abnormal in 15 (18.8%). With a mean age of 21 months, 63
      children (75.9%) had normal motor development and 20 (24.0%) had motor
      abnormalities. The cognitive development was normal in 68 children (81.9%). The
      negative predictive value of the cerebral ultrasonography for motor development
      was 85.3%, and for cognitive development, 86.8%. The positive predictive value of
      the cerebral ultrasonography for motor development was 66.7% and for cognitive
      development, 42.9%. CONCLUSIONS: The negative predictive values were greater than
      the positive predictive values in both areas of development. The probability for
      children with normal neonatal ultrasonography to have normal motor and cognitive
      development is greater than 85%.

PMID- 14685564
TI  - [Risk factors for neonatal asphyxia in neonates weighing more than 1000 grams]
AB  - OBJECTIVE: To evaluate some of the risk factors for neonatal asphyxia in neonates
      weighing more than 1000 grams. METHODS: In a population of 13.385 consecutive
      deliveries, from January 1991 to December 1994, 135 newborns with neonatal
      asphyxia were compared with 135 without the disease, in a casecontrol study,
      matched by birth weight, at the Neonatology Unit of the Pediatric Department of
      the Universidade Estadual de Campinas (UNICAMP). The statistical analysis
      employed was bivariate and multiple by logistic regression, and expressed as odds
      ratio (OR) with 95% confidence intervals. RESULTS: In the bivariate analysis, the
      factors significantly associated with asphyxia were: abruptio placentae [OR =
      8.00 (1.07-353.4)], cesarean section [OR = 2.94 (1.64 -5.55)], breech
      presentation [OR = 3.33 (1.54 - 7.98)], abnormal fetal heart rates [OR = 4.88
      (2.25-12.08)], prolonged rupture of membranes [OR = 4.33 (1.19-23.71)], a
      meconial hemorrhagic or infected amniotic fluid [OR = 9.00 (3.58 - 29.03)],
      oligohydramnios or polyhydramnios [OR =5.00 (1.88 - 16.76), use of anesthesia [OR
      = 2.56 (1.41 - 4.89)] and general anesthesia [OR = 14.00 (2.13 - 598.8)], male
      sex [OR = 2.06 (1.12 - 3.92)] and a gestational age of less than 37 weeks [OR =
      3.29 (1.37 - 9.07). After multiple analysis, abnormal amniotic fluid,
      oligohydramnios or polyhydramnios, and anesthesia were the only factors
      associated with neonatal asphyxia, and more than six prenatal visits was a
      protector factor. CONCLUSIONS: Obstetrical, perinatal and neonatal clinical
      events are associated with neonatal asphyxia, that concerted efforts to provide
      adequate prenatal care, optimal assistance during delivery and birth, and
      appropriate neonatal intensive care should significantly reduce neonatal
      morbidity and mortality.

PMID- 14685565
TI  - [Associated and prognosis in apparent life threatening events (ALTE)]
AB  - OBJECTIVE: To verify the etiology and prognosis of ALTE in infancy and its
      possible relationship to Sudden Infant Death Syndrome (SIDS). METHODS: We studied
      a group of infants that presented ALTE episodes and were evaluated in our
      hospital. First we reviewed their clinical history and polysomnographies, then we
      sent a letter to the families with questions regarding the outcome. RESULTS: 56
      patients were included. 92% had ALTE during their first 6 months and 83% in the
      first trimester. Symptomatic ALTE predominated (71%). The disease most frequently
      associated was gastroesophageal reflux, followed by neurological diseases. The
      follow up showed 51.5% of normal outcome, 4 children repeated ALTE, no cases of
      SIDS were registered. CONCLUSIONS: Our results showed that multifactorial
      etiologies can be associated to ALTE, and the outcome is generally related to the
      associated disease. We did not observe any relationship between ALTE and SIDS
      considering a predominantly symptomatic ALTE population.

PMID- 14685566
TI  - [Acute intermittent porphyria in childhood]
AB  - OBJECTIVE: Porphyries are metabolic disorders of the haem biosynthetic pathway.
      They result from excessive accumulation of neurotoxic porphyrin precursors.
      Unlike the majority of Inherited Metabolic Diseases, the porphyries manifest
      after puberty, and their occurrence in childhood is very rare. PATIENT AND
      METHOD: The authors report a case of acute intermittent porphyria in an 8-year
      old girl, reviewing the literature on etiopathogeny, diagnosis and treatment.
      COMMENTS: The authors emphasize to the importance of diagnosis in these patients,
      since the clinical expression may be lifethreatening and requires exposures to
      precipitating factors, so it may be prevented.

PMID- 14685567
TI  - [Cutis laxa associated to cardiac failure]
AB  - OBJECTIVE: To focus attention on a rare pathology of the childhood which presents
      premature aging of the skin and can be lethal. METHODS: The authors present a
      case of cutis laxa, syndrome of premature aging, in an eight year-old child, and
      discuss the classification, diagnosis and prognosis of the disease. RESULTS: The
      child presented signs of premature aging when he was four years-old. The
      diagnosis of cutis laxa was confirmed by skin biopsy. The patient presented heart
      failure, a systemic complication different from those previously described, and
      died at eight years of age. CONCLUSIONS: The importance of the diagnosis of cutis
      laxa resides in the fact that besides characteristic dermatological findings,
      there are frequent systemic complications that can be the focus of preventive
      measures, since there is no specific treatment for this disease. Genetic
      counseling is another important issue in this condition.

PMID- 14685568
TI  - [Supplements of the Jornal de Pediatria: a new jornal or widening the scope?]

PMID- 14685569
TI  - [Immune system and infections]
AB  - OBJECTIVE: The aim of this review is to present some aspects of the immune
      system.METHOD: Review of the literature, covering some of the most important
      aspects to the pediatrician.RESULTS: We describe characteristics of the immune
      system when presented to different antigens, and cells and cytokines effector
      functions. We also discuss aspects of immaturity of the immune system observed in
      the pediatric group.CONCLUSION: It is very important that the pediatrician
      understands how the immune system works.

PMID- 14685570
TI  - [The impact of the environment upon the respiratory tract]
AB  - OBJECTIVES: Air pollution has been a significant worldwide problem with
      repercussions in the respiratory tract, along the years. The main objectives of
      this review are to present results from studies on the harmful effects of
      allergens as well as of pollutants over the respiratory tract.METHOD: Published
      studies were analyzed in respect to each agent involved, either environmental
      pollutants or allergens.RESULTS: There has been a remarkable increase in the
      prevalence of asthma and allergies in Western countries children, during the last
      decades, which involves participation of many environmental factors. The house
      dust mites allergens followed by pet allergens have been classified as one of the
      most important causes of early sensitization, in genetically susceptible
      individuals. It became of utmost importance to determine the action of pollutants
      in the airways of asthmatic patients, once asthma is an inflammatory disease with
      an outstanding surge of inflammatory cells, affecting airway mucosal. Among the
      environmental agents, tobacco smoke, NO(2), O(3) and the CO are associated to the
      increase in morbidity, with specific harmfulness.CONCLUSION: There are evidences
      that the higher exposure to indoor allergens, to pollutants and irritants,
      associated to changes in diets, changes in the exposure pattern to infectious
      agents and the use of antibiotics are leading to an increase in respiratory
      diseases over the last 30 years.

PMID- 14685571
TI  - [Acute and secretory otitis media]
AB  - OBJECTIVE: Otitis media is the most frequently diagnosed infection in the
      pediatric office. Ninety per cent of the children present at least one episode of
      otitis media before the fifth birthday. We reviewed the literature in order to
      update information regarding the current definitions of acute otitis media,
      recurrent otitis media and otitis media with effusion, analyzing the predisposing
      factors, microbiology, clinical manifestations, diagnostic criteria and methods
      of treatment for these entities, and the relationship between otitis media and
      language development and learning disabilities.DATA SOURCE: Bibliographic review
      of an eighteen- year period (1980-1998) using Index Medicus and Medline.RESULTS
      AND CONCLUSIONS: More than 25 million diagnoses per year of middle ear infections
      are made in the United States, being responsible for rising costs of treatment.
      The role of many predisposing factors is presently well recognized and we should
      be capable of defining interventions related to some of them as is the case of
      early institution of day-care, short duration of breast feeding and difficulties
      in the identification and treatment of gastroesophageal reflux. Changes in the
      microbiology of the middle ear infections and the emergence of multiresistant
      bacteria leads to modifications in antibiotic therapy and the duration of its
      use. Antibacterial agents should be prescribed only in the presence of a well
      defined diagnosis and chemoprophylaxis should be avoided. Recurrent otitis media
      and otitis media with effusion in infants may be associated to speech disorders
      and learning disabilities. The development of a conjugated vaccine against S.
      pneumoniae and the experiments with a vaccine against non-typeable H. influenzae
      represent a big step in the prevention of infections of the middle ear for the
      near future.

PMID- 14685572
TI  - [Rhinosinusitis in children]
AB  - OBJECTIVES: To review the pathogenic mechanisms and treatment of sinusitis in
      children.METHODS: Mucopurulent secretion and halitosis are important signs and
      symptoms for the diagnose of sinusitis. The radiographic and computorized
      tomography investigations confirm the sinusal disease.RESULT: The identification
      of the main pathogens involved in the acute and chronic sinusitis is fundamental
      to give a better therapeutic control to these patients. CONCLUSIONS:
      Rhinosinusitis is one of the most reported diseases among the general population,
      and its prevalence has been rising in the last years. Many questions remain
      unanswered about its cause, pathophysiology and optimal treatment, especially in
      the pediatric population, generating health care costs and a high rate of
      morbidity.

PMID- 14685573
TI  - [Acute viral bronchiolitis - still subject for controversy]
AB  - OBJECTIVES: The authors review the current literature on acute viral
      bronchiolitis discussing the points still subject to controversy in regard to its
      treatment. At the same time, a personal point of view on the management of this
      disorder based on the authors experience is also expressed.METHODS: The main
      published papers from the last twenty years were selected from a Medline database
      search.RESULTS: Acute viral bronchiolitis is an acute viral illness of the lower
      respiratory tract occuring most frequently during the first year of life. In
      spite of its important prevalence and the relative risk that this disorder may
      pose to pediatric patients there is still a lot of controversy in regard to its
      treatment. However, it seems of paramount importance to mainten an adequate
      hidration, to prevent cross infection and to offer supplementary oxygen. There
      are many doubts as to the role of bronchodilators and antivirals such as
      ribavirin. There are new hopes with the introduction of specific immunoglobulin,
      mostly as a prophylactic role in respiratory syncycial virus infection in at risk
      populations. Steroids seem to have no place in the treatment at least in the
      acute stages of the disease. CONCLUSIONS: Acute viral bronchiolitis is still a
      disorder which lacks a specific treatment. The routine treatment has little
      changed for the last 30 years and there is controversy in regard to its
      management in the different clinical centers.

PMID- 14685574
TI  - [Asthma in children: classification and treatment]
AB  - OBJECTIVES: To review concepts, classification based on severity, and long term
      treatment for children with asthma. METHODS: To identify precipitating factors of
      acute asthma attacks and classify the disease in order to establish long term
      treatment. RESULTS: Different plans of management according to its
      classification: mild, moderate and severe asthma. Antiinflammatory therapy is
      reserved to moderate and severe asthma. CONCLUSIONS: The identification and
      control of the etiologic and precipitating factors are important tasks in the
      management of asthma. The inhalatory route is the most appropriate to treat
      patients suffering from asthma. The usual drugs indicated in asthma treatment are
      reviewed. Precocious treatment with inhaled glucocorticosteroids is recommended
      by several authors.

PMID- 14685575
TI  - [Severe acute asthma in the child]
AB  - OBJECTIVE: To present a current review about diagnosis and treatment of severe
      acute asthma, based on the reviewed publications and the authors personal
      experience. METHODS: We reviewed the most relevant articles about diagnosis and
      management of severe acute asthma. RESULTS: Severe acute asthma is an important
      cause of morbidity in children and it can usually lead to respiratory failure.
      The diagnostic (clinical manifestations and lung function tests) and treatment
      (oxygen, bronchodilators and steroids) are now well determined by the literature,
      and are very important for a good prognosis of every patient. CONCLUSIONS:
      Considering severe acute asthma a prevalent condition in pediatric emergency room
      and intensive care unit, the ability to make an early diagnosis of this
      condition, associated with a prompt treatment, are essential for an effective
      reduction in morbimortality rates.

PMID- 14685576
TI  - [Childhood tuberculosis]
AB  - OBJECTIVE: This review paper on tuberculosis in children aims at describing the
      classical pathogenic findings and to discuss practical features for diagnosis,
      treatment and prevention, based on Brazilian official rules. METHODS: The author
      reviews the last 5 years literature on the subject using as sources Medline,
      Ministry of Health official publications and Brazilian medical publication not
      included in the Index Medicus, as well. RESULTS: A fluxogram is described for the
      diagnosis of tuberculosis in children and presented as a proposal for
      implantation in low complexity health services. Figures displaying tuberculosis
      treatment models proposed by the Ministry of Health are also showed. New
      prevention concepts introduced in the last 5 years are presented. CONCLUSIONS:
      Tuberculosis in children remains a diagnostic challenge. Treatment rules have
      been well defined. Prevention measures should be reinforced.

PMID- 14685577
TI  - [Cystic fibrosis]
AB  - OBJECTIVE: Due to the great advances recently achieved in the treatment of Cystic
      Fibrosis as well as to the fact that pediatricians need to have a better
      understanding of this disease, the authors propose an extensive review of the
      subject. METHODS: We selected the most outstanding publications on Cystic
      Fibrosis in the international literature of the recent years, with the purpose of
      being up-to-date and at the same time offering a practical synthesis for the
      readers. RESULTS: We elaborated an extensive review about Cystic Fibrosis
      covering the following topics: historical remarks, genetics, physiopathogenesis,
      microbiology of pulmonary infections, clinical manifestations, clinical and
      laboratorial criteria for diagnosis, differential diagnosis, treatment and
      prognosis.

PMID- 14685578
TI  - [Bronchopulmonary dysplasia]
AB  - OBJECTIVE: To review the literature on bronchopulmonary dysplasia. METHODS: The
      most important articles on bronchopulmonary dysplasia were selected through
      MEDLINE. RESULTS: The present review analyzes the different concepts,
      pathogenesis, clinical presentation, treatment and prophylaxis of
      bronchopulmonary dysplasia. CONCLUSIONS: bronchopulmonary dysplasia is a frequent
      condition of very low birth weight infants with hyaline membrane disease who
      require mechanical ventilation. The pathogenic factors are prematurity, oxygen
      therapy, mechanical ventilation, pulmonary edema, and infection. Treatment is
      based on good oxygenation, fluid restriction, nutritional support, diuretics,
      betamimetic drugs, xanthines, and steroids. Prophylaxis includes avoiding
      prematurity and using pre-natal steroids, superoxide dismutase, and post-natal
      steroids.

PMID- 14685579
TI  - [Respiratory failure in the child]
AB  - OBJECTIVE: To describe the main physiopathologic mechanism of the respiratory
      failure in the child, as well as to discuss some aspects of the differential
      diagnosis and treatment. SOURCE OF DATA: The main national and international
      textbooks and articles about respiratory failure in the child were used as
      sources of data for this research. RESULTS: Respiratory failure is defined as the
      incapacity to maintain a paO(2) over 50 mmHg associated or not to a paCO(2) over
      50 mmHg in children breathing ambient air at sea level. This failure may be
      classified as hypoxemic or hypercapnic, or even as acute or chronic. The main
      alterations may be hypoventilation, ventilation perfusion mismatch and diffusion
      defect. It may be secondary to a central origin, upper or lower airway
      compromise, parenchyma disease, or due to pleural or thorax wall affection. The
      hypoxemia evaluation may be done by hemoglobin saturation, alveolar capillary
      gradient of oxygen (D[A-a]O(2)) or by the paO(2) / FiO(2) index. COMMENTS: The
      knowledge of the physiopathologic mechanisms that cause respiratory failure in
      the child is important to define the more efficient therapeutic strategy for each
      cause.

PMID- 14685580
TI  - [Mechanical ventilation in children]
AB  - OBJECTIVE: To make a brief review about mechanical ventilation in
      Pediatrics.METHODS: Review of the classification of types of mechanical
      ventilation, characteristics of pression and flow waves and indications for its
      installation. In a sequential way we discuss the various modes of ventilation
      (control ventilation, assisted-control ventilation, assisted ventilation,
      intermittent mandatory ventilation, synchronized intermittent mandatory
      ventilation, pressure-support ventilation) showing some advantages and
      disadvantages of using these modes. RESULTS: General rules for mechanical
      ventilation are presented, considering some specific pathologies in Pediatrics
      (acute respiratory distress syndrome, bronchopleural fistulae, cranial trauma,
      cardiac failure, neuromuscular pathology, acute asthma and in patients with acute
      descompensation of a cronic respiratory failure). CONCLUSIONS: Some limitations
      of mechanical ventilation and the possible advances in a short period are
      presented.

PMID- 14685581
TI  - [Laboratorial tests in pulmonary diseases]
AB  - OBJECTIVE: The authors present a review about the diagnosis of pulmonary
      diseases, with special emphasis on laboratorial procedures. METHODS: The most
      important articles about laboratorial procedures were selected through Medline
      search. RESULTS: To diagnose pulmonary diseases we need to evaluate clinical
      history, laboratorial tests, several radiografic techniques, bronchoscopy,
      thoracentesis and lung biopsy among others. We present the main laboratorial
      tests which include the clinical tests and pulmonary function evaluation to
      diagnose these diseases. CONCLUSION: The laboratorial tests are part of pulmonary
      tests diagnosis. The obtained results should be associated with clinical history
      and the other diagnostic methods.

PMID- 14685582
TI  - [Continuous intravenous terbutaline for childhood severe acute asthma]

PMID- 14685583
TI  - [Transient neonatal tyrosinemia - disease or variation in normal patterns?]

PMID- 14685584
TI  - [IgA deficiency]
AB  - OBJECTIVE: The studies about immunoglobulin A (IgA) deficiencyin the clinical,
      laboratorial and terapeutic aspects. METHODS: Bibliografic review of the last ten
      years about thesubject by Medline system and direct research. RESULTS AND
      CONCLUSIONS: IgA deficiency is the most frequent primary immunodeficiency, with
      the average prevalence of 1:700and must be studied in its clinical, laboratorial
      and terapeutic aspectsby pediatrician and other specialists. The clinical
      characteristics ofthe total and partial immunodeficiency must be known, so as
      thecomplications and laboratory techniques for determine accurate diagnosis and
      prognostic.

PMID- 14685585
TI  - [Intravenous terbutaline in children]
AB  - OBJECTIVE: The authors describe their experience with theuse of intravenous Beta2
      adrenergic (IV terbutaline) in patientsadmitted to a PICU with severe lower
      airway obstruction. PATIENTS AND METHODS: A retrospective study of all admissions
      to a PICU was conducted in Santo Antonio Hospital in Porto Alegre (Brazil) during
      the winter of 1995. The files ofall the patients that were treated with
      intravenous Beta2 adrenergicas a bronchodilator were selected. The analysis
      included lengthof use, initial doses, maximal doses, associated
      phenomena,arterial blood gases and plasma level of potassium. RESULTS: During the
      three months of study 367 patients wereadmitted to the PICU and 38 (10.3%) used
      IV terbutaline. Thisgroup of patients had a mean age of 13.8-/+12.2 months old
      andused IV terbutaline for a mean length of 7.24-/+3.6 days. Theinitial rate of
      infusion was 0.55-/+0.25 mcg/kg/min with a meantherapeutic dose of 2.45-/+1.18
      mcg/kg/min. Twelve patients(31.5%) had increase in their heart rate (over 180
      bpm) thatprevented increases in the infusion rate. However this was atemporary
      effect. The patients under 12 months of age startedwith low infusion rates (0.45
      /+0.22 mcg/kg/min), when comparedto children over 1 year old (0.57-/+0.3
      mcg/kg/min), p <0.01. No patient developed pathologic heart rate attributed to
      the drug. The serum levels of potassium decreased significantly (p <0.01) only in
      the group of patients under 1 year (4.1-/+0.7 to 3.47-/+0.52 mEq/L), but this
      difference had no clinical relevance. COMMENTS: In view of these results the
      authors showed that the infusion of IV terbutaline in children is safe and
      presents alow risk if the criteria of administration and monitoring are followed.
      In this manner, IV terbutaline is an excellent therapeuticoption for children
      with severe lower airway obstruction andno response to the conventional
      treatment.

PMID- 14685586
TI  - [Transient neonatal tyrosinemia: a frequent abnormality]
AB  - OBJECTIVE: To evaluate the frequency of transient neonatal tyrosinemia, with or
      without secondary hyperphenylalaninemia,observed through neonatal screening for
      metabolic disorders, andthe need of monitoration and intervention with drugs
      and/or specialdiet in selected cases. METHODS: 457.870 dried blood samples
      obtained by heel stickfrom 3 to 20 days old babies were qualitatively evaluated
      by aminoacid thin-layer chromatography. Positive cases were
      quantitativelyconfirmed in serum samples by fluorimetric measurement of
      tyrosineand phenylalanine. RESULTS: 1.231 dried blood samples displayed positive
      resultsfor tyrosine in the cromatographic evaluation. The fluorimetricserum
      analysis disclosed normal levels of tyrosine and phenylalaninein 822 patients.
      The remained 409 patients showed hightyrosine levels and were placed in three
      groups according to thetyrosine concentration. In 118 of these cases serum
      phenylalaninewas also increased. CONCLUCIONS: Transient neonatal tyrosinemia is a
      very frequentdisorder in neonates (1/372); in some cases very high levels
      werefound, not only of tyrosine but also phenylalanine. As this findingis not yet
      accepted as absolutely harmless, the monitoration of thissituation and the use of
      measures to lower the tyrosine and phenylalaninelevels should be considered by
      the pediatrician.

PMID- 14685587
TI  - [Chronic functional constipation in children: diagnosis and prevalence in a low
      income community]
AB  - OBJECTIVE: To investigate the prevalence of chronic functionalconstipation in
      children aged under 11 years of a low-incomecommunity in Recife, Northeast Brazil
      and to assess the validity ofcomplaints of bowel habits for the diagnosis of
      constipation. METHODS: A community-based survey identified 536 eligiblechildren.
      Data collection was home-based through a structuredquestionnaire applied to the
      mothers. The definition of chronicfunctional constipation was based on painful
      defecation or witheffort, with stools of hard consistency and/or frequency of
      defecationless than three times per week, during at least the last thirty days.
      RESULTS: The prevalence of chronic functional constipation was17.5%. Straining
      was the complaint which obtained the highestsensitivity for the diagnosis of
      constipation (96.8%) while pain todefecate obtained the highest specificity
      (99.5%). CONCLUSIONS: Chronic functional constipation was a prevalentsymptom in
      this community, pointing out to the need of an activesearch in paediatric
      consultation. Straining was identified as thesingle complaint which better
      diagnosed constipation.

PMID- 14685588
TI  - [The use of clinical score to estimate the severity of an acute attack of asthma]
AB  - OBJECTIVE: To identify patients with acute asthma who require intensive care,
      using a clinical score.METHODS: Retrospective analysis of 299 patients who were
      admitted to the hospital for acute asthma, between 1993 and 1996. Two groups were
      selected: group I (GI) with 26 patients admitted to the Intensive Care Unit;
      group II (GII) with 52 patients admitted to the Emergency Room, matched by age
      and sex with those of GI. A clinical score to assess the groups had the following
      items: heart rate, respiratory rate, retractions, cyanosis, alertness level,
      previous treatment, previous hospitalization, and duration of attack. The score
      ranged from 0 to 2 points for each of those, summing up 11 points.RESULTS: The
      clinical parameters that discriminated well the 2 groups were: retractions
      (p<0.001), cyanosis (p<0.01) and alertness level (p<0.005). Through a
      discriminate analysis of the clinical score components, 22/26 patients were
      recognized as GI and 40/52 patients were recognized as GII, showing an accuracy
      of 85% and 77% respectively for GI and GII.CONCLUSION: The clinical score was
      useful to discriminate patients with severe attack of asthma who might require
      intensive care, and should be employed at hospital admission.

PMID- 14685589
TI  - [Efficacy and safety of cefprozil versus cefaclor in the treatment of acute
      otitis media in pediatric patients]
AB  - OBJECTIVE: To evaluate the efficacy and safety of two oral cephalosporins,
      cefprozil and cefaclor, in the treatment of acute otitis media in
      children.METHODS: Forty children with clinical diagnosis of acute otitis media
      were randomized in two groups. Twenty-one children were given cefprozil at the
      dose of 30/mg/kg/day, in two equally divided doses every twelve hours, for ten
      days. Nineteen children were given cefaclor at the dose of 40/mg/kg/day in three
      divided doses every eight hours, for ten days. Efficacy evaluation of the
      antibiotic was analyzed by the presence or absence of symptoms, fever and
      otoscopic abnormalities while the safety and tolerability were evaluated by
      spontaneous information for possible adverse events.RESULTS: There was a
      significant decrease in the number of observed alterations between days 3 and 5
      of treatment among those of the cefprozil group in comparison to the cefaclor
      group, while between days 10 and 14 of treatment the observed cure rate was
      clinically similar in both groups. Both medications presented adequate safety
      profiles. Only three children receiving cefprozil presented mild adverse events,
      such as nausea and vomit, none of which required treatment
      interruption.CONCLUSIONS: The clinical efficacy of both cephalosporins was
      similar although a more rapid activity was observed for cefprozil between days 3
      and 5 of treatment. The favorable clinical results, the low incidence of adverse
      events and the twice a day dose regimen suggest that cefprozil is one more
      antimicrobial of choice for the treatment of acute otitis media in children, when
      this therapeutic is indicated.

PMID- 14685590
TI  - [Serologic survey of rubella in the pre-vaccine era in child-care centers,
      schools and maternity units of Fortaleza]
AB  - OBJECTIVES: To identify rubella prevalence in different ages and population
      groups and rubella susceptibility of pregnant and postpartum women according to
      age, number of children and spontaneous abortion. METHODS: Cross-sectional study
      of sero-survey type. Children and students were selected in day-care centers and
      schools distributed by health districts of Fortaleza. Pregnant and postpartum
      healthy women were recruited in two large maternity units and three antenatal
      clinics; individuals previously vaccinated and presenting chronic or acute
      diseases where excluded. Written consent was obtained from participants or their
      caretakers. Anti-rubella IgG qualitative detection was performed with an Elisa
      sandwich assay. RESULTS: Mean age-specific sero-prevalence rates of 999 samples
      were: 2 to 5 years= 59% (136/231); 6 to 9 years= 47% (95/204); 10 to 19 years=
      56% (243/432) and 20 to 39 years= 80% (106/132). The mean age of 187 pregnant and
      postpartum women was 23 years (10-39) with a sero-prevalence of 76% (142/187),
      where 62% sero-positives aged 15 to 19 and 83% aged 26 to 39 years. A higher sero
      prevalence was related to womens age (p<0.001), history of spontaneous abortion
      (p= 0.03), and two or more children (p=0.01). CONCLUSIONS: The high sero
      prevalence of rubella in preschool age children reflects the intense viral
      transmission in child-care centers. The high susceptibility in adolescents (45%),
      among whom pregnancy is common, emphasizes the need to introduce rubella vaccine
      early and keep high immunization coverages in youngsters in order to eradicate
      congenital rubella syndrome. Also, postpartum routine immunization against
      rubella in this age group is of particular benefit.

PMID- 14685591
TI  - [Bartter's syndrome: two case reports in childhood]
AB  - OBJECTIVE: To report a syndrome that is uncommon in childhood and call
      pediatriciansattention to the tubular diseases - just like Bartters syndrome - in
      differential diagnosis of failure to thrive and other diseases that can be
      usually found in children.METHODS: Two patients are presented. The first, a 3
      years and 2 months old boy who was submitted for investigation of a failure to
      thrive detected when he was 9 months old. The second patient, a 3 months old
      girl, was admitted to the Intensive Care Unit due to severe electrolyte
      disturbances. She was supposed to have a pyloric hypertrophic stenosis.RESULTS:
      Both patients had failure to thrive, hypocloremic alkalosis, hypokalemia, and
      hypercalciuria. The first had a positive obstetric history for polihydramnios
      that is frequently found in the neonatal form of this syndrome. Treatment was
      done by blood potassium correction, together with indometacin and spironolactone
      administration. These drugs where well tolerated by the patients who have
      improved their growth rhythm only a short time after electrolytic disturbances
      had been corrected.CONCLUSIONS: The Bartter's syndrome is a tubular disease that
      is unusual in childhood. It must be considered as a possible cause of failure to
      thrive. The neonatal form is rare and can produce severe hydro-electrolytic
      disturbances, increasing the difficulties for diagnosis. The treatment is well
      tolerated, even by small children, and must begin early to reduce the troubles to
      thrive.

PMID- 14685592
TI  - [The importance of chest radiograph in the diagnosis of Scimitar syndrome]
AB  - OBJECTIVE: To emphasize the importance of chest X-Rays in the diagnosis of
      Scimitar Syndrome. This anomaly is usually characterized by the presence of
      anomalous venous drainage of the right lung to the inferior vena cava, abnormal
      bronchial segmentation, and alterations of pulmonary artery and right lung
      vascularization.METHODS: The authors report a case of Scimitar Syndrome in an 8
      year-old-child, discussing its diagnostic methods and surgical treatment.RESULTS:
      The child presented good outcome after surgical therapy, with an uneventful
      follow-up.CONCLUSION: The Scimitar Syndrome is a rare anomaly, which may present
      few clinical manifestations. The chest X-Ray is a very relevant tool in the
      screening of this disease, since it discloses a persisting right paracardiac
      image, as a result of abnormal right pulmonary venous drainage to inferior vena
      cava ("Scimitar sign").

PMID- 14685593
TI  - [Otoscopy and tympanometry in the diagnosis of secretory otitis media]

PMID- 14685594
TI  - [Strategies to increase the practice of breastfeeding]

PMID- 14685595
TI  - [Sleep evolution from fetal life to adulthood: respiratory and neurologic
      aspects]
AB  - OBJECTIVE: This article has the purpose of presenting some basic concepts about
      sleep, besides offering a brief review of the main ventilatory and neurologic
      changes during sleep, from fetal life up to adulthood. METHODS: Bibliographic
      review of international literature including original articles and textbook
      chapters.RESULTS: The sleep-wake cycle undergoes changes from fetal life to
      adolescence, both in duration (the fetus sleeps most of the time in utero, and
      the adult sleeps about 8 hours a day), and in its distribution throughout the day
      (the newborns sleep is fragmented and occur during the day as much as during the
      night; the adultacute;s sleep is a single stage that happens at night). The sleep
      has two basic stages: Non-REM and REM sleep. From the respiratory standpoint,
      physiologic changes can be appreciated along the time, being infants more
      susceptible to respiratory events during sleep than adults. CONCLUSIONS: The
      recognition of the value of sleep and its effects on human organisms has been
      growing, specially in the last two decades, with the establishment of the first
      sleep disorders centers. The expressive scientific work developed in this area
      has provided us with a better understanding of this neurologic state in wich we
      spend about half of our lives.

PMID- 14685596
TI  - [Otoscopy and tympanometry in the diagnosis of secretory otitis media]
AB  - OBJECTIVE: To study the sensitivity and specificity of otoscopy and tympanometry
      in the diagnosis of secretory otitis media. METHODS: A prospective study was
      performed in 98 children (196 ears) with indication of myringotomy with placement
      of tympanostomy tube because of the diagnosis of secretory otitis media. All
      these patients had conductive hearing loss and/or delay of speech and/or low
      school performance. To evaluate the diagnostic power of the tests, both otoscopy
      and tympanometry were performed. Myringotomy was established as the gold
      standard. The statistical analysis was done using the chi-square test, being
      significant a p<0.05.RESULTS: The mean age of the patients was 6.02 years (sd:
      2.93 years). The otoscopy presented sensitivity of 87.5% and specificity of 61.1%
      and the tympanometry presented sensitivity of 93.75% and specificity of 72.2%.
      CONCLUSIONS: There was no statistically significant difference in sensitivity
      between otoscopy and tympanometry for the diagnosis of secretory otitis media,
      however, tympanometry was significantly more specific than otoscopy (p< 0.01).

PMID- 14685597
TI  - [A simple strategy increases mother's knowledge of breastfeeding and improves the
      breastfeeding rates]
AB  - OBJECTIVE: To assess mother's knowledge of breastfeeding before and after
      guidance supplied during the postpartum period and its relationship to the
      prevalence of breastfeeding.METHODS: A clinical trial was performed with 405
      mothers of normal children born at Hospital de Clinicas de Porto Alegre from July
      to December 1994. The intervention consisted of guidance given by means of a
      video film discussing basic topics on breastfeeding, an explanatory leaflet and
      open discussion after the video. The first 208 mothers constituted the Control
      Group and the remaining 197 the Experimental Group. All mothers answered a
      question form for identification purposes and a test on previous knowledge
      regarding breastfeeding in the maternity ward. The mothers in both groups were
      followed by means of home visits at the end of the first, second, fourth and
      sixth months, or until they stopped breastfeeding. At the end of the first month
      the mothers were submitted to the same test given right after delivery. Logistic
      regression was used to evaluate the association between the mothers knowledge of
      breastfeeding and the prevalence of breastfeeding.RESULTS: The mothers who
      received the intervention (Experimental Group) had a significantly higher score
      in the tests on knowledge of breastfeeding at the end of the first month as
      compared with the mothers in the Control Group (17.0 versus 14.7). The
      intervention increased by 1.7 mothers chances of achieving a score above the
      average. The mothers whose scores were above the average had a 8.2 higher chance
      of being breastfeeding exclusively at the end of the third month and twice as
      high of still being breastfeeding at the end of the sixth month.CONCLUSION:
      Simple strategies to increase mother's knowledge regarding breastfeeding can have
      a positive impact on breastfeeding rates.

PMID- 14685599
TI  - [Congenital hypothyroidism screening: seasonal variations of TSH levels]
AB  - OBJECTIVE: To evaluate the seasonal differences in newborn TSH levels. METHOD: A
      restrospective study was performed using normal blood TSH measurements collected
      in a neonatal screening program for congenital hypothyroidism, during the
      extremes of temperature (summer/winter) in order to verify the seasonal influence
      on that exam. Blood samples were collected from baby feet on filter paper in
      health care public institutions in Rio de Janeiro city and TSH were analyzed by
      immunofluorimetric method. For this study we considered samples with TSH levels
      less then 20 micro U/ml. The factors age, birth weight and prematurity were all
      observed.RESULTS: We evaluated 388 measurements: 159 in the summer and 229 in the
      winter. Newborn and infants aged from 2 days to 3 months were included. The time
      of collection of the exam was significant in the measurement of TSH and the mean
      levels of TSH collected in the summer were somewhat higher than those collected
      in the winter (p = 0,0001), when analyzed by the t-test, even so when the age was
      taken into account. Using F-test (p=0,0234) we observed differences between TSH
      levels in age groups. TSH levels in the newborn with 2 to 7 days of age differ
      significantly from those of higher age. Birth weight and prematurity do not show
      interference with the TSH measurement.CONCLUSIONS: Newborn and infant TSH levels
      were significantly higher in the summer than in the winter.

PMID- 14685598
TI  - [Bacterial contamination of breast milk collected through manual expression and
      stored at room temperature]
AB  - OBJECTIVES: To the determine the bacterial contamination profile of unheated
      expressed breast milk, collected without rigid hygienic precautions and stored at
      room temperature for nine hours. The purpose was to give poor lactating mothers
      the alternative of storing their own milk out of refrigerator. A research on
      cultural, social and economical aspects as well as on donators knowledge about
      breastfeeding was considered necessary. METHODS: 35 donators were interviewed and
      an experimental investigation was performed with 33 samples of breast milk stored
      at room temperature (17 masculine C to 30.5 masculine C) and bacteriologically
      analyzed at zero, three, six and nine hours after collection. The same breast
      milk was stored at refrigerator (2 masculine C to 6 masculine C) as a control
      procedure. Total count of bacterial contents and identification of Staphylococcus
      aureus and Escherichia coli were evaluated.RESULTS: The enterviews revealed the
      low socio-economical and cultural level of lactating mothers and their little
      experience in expressing, collecting and using their own milk. Bacteriological
      data analysis showed mesophyllous average of 7.1x10(3)UFC/mL, acceptable outline
      of bacterial contamination, despite the use of a simplified hygiene technique.
      After nine hours, samples stored at room temperature showed final average of
      bacterial contents similar to the first ones (7.3x10(3)UFC/mL) and without
      relevant statistic differences from the ones kept under refrigeration (p=0.05)
      for studied bacterias.CONCLUSION: This study shows that it is possible to use
      unprocessed breast milk for babys consumption if it is stored at room
      temperatures until nine hours after it has been collected. However, mothers have
      to be told about the possibility of storing breast milk for babies later
      consumption.

PMID- 14685600
TI  - [Hyperglycemia and glucosuria in preterm infants receiving parenteral glucose:
      influence of birth weight, gestational age and infusion rate]
AB  - OBJECTIVE: Morbidity and mortality of premature infants have decreased
      considerably over the last decades, therefore, adequate nutrition of the
      premature is a major concern. Enteral feeding is the route of choice, but when it
      is not possible the parenteral route, which contains glucose as one of its main
      components, is used. Glucose infusions are not devoid of risk as they facilitate
      the development of hyperglycemia leading to intracranial hemorrhage, glucosuria
      and dehydration. The aim of this paper is to relate hyperglycemia and glucosuria
      to birth weight, gestational age and glucose infusion rate.METHODS: The study was
      developed at the Nursery of Santa Catarina Hospital (Sao Paulo). The authors
      developed a prospective study; 511 concurrent determinations of glycemia and
      qualitative glucosuria were performed in 40 preterm newborn infants receiving
      parenteral glucose (mean of 12.8 dosages per newborn).RESULTS: Fifty-nine (11.5%)
      episodes of hyperglycemia were detected, and their frequency was higher at lower
      gestational ages (</=34 weeks), lower birth weights (< 1500g) and higher glucose
      infusion rates (>/= 6 mg/kg/min). Thirty-one (6.1%) episodes of glucosuria were
      detected, and were more frequent in lower gestational ages (</= 34 weeks), lower
      birth weights (< 1500g) and higher glucose infusion rates (>/= 6
      mg/kg/min).CONCLUSIONS: The frequency of hyperglycemia and glucosuria in preterm
      newborn infants receiving glucose infusion was higher in lower gestational ages,
      lower birth weights and higher glucose infusion rates. In preterm newborn infants
      it is necessary to observe the glucose infusion rate and its respective glycemia,
      in order to avoid the complications of hyperglycemia.

PMID- 14685601
TI  - [Public and private day-care centers in Pelotas, RS: compliance with the
      regulations]
AB  - OBJECTIVES: Seventy-seven day-care centers were evaluated in Pelotas, RS, Brazil,
      in 1996, in order to assess compliance with current service regulations. METHODS:
      Information about physical structure, facilities, equipment, hygiene practices,
      and day-care staff was collected through a structured questionnaire. RESULTS: The
      median number of children in public day-care centers was 89 children per center,
      while in the private centers the median was 29 children per center (p<0.001). A
      nursery was available in 88% of public day-care centers, and in 36% of the
      private centers (p<0.001). Concerning the physical structure, the majority of the
      public centers had exclusive toilet facilities for the children (91%), while this
      was the case in only 66% of the private centers (p<0.001). Fire extinguishers
      were found in public centers in a proportion three times higher than in the
      private centers. Proper bottle washing and refrigeration was done in 95% of the
      day-care centers studied, while sterilization of the bottles was reported in only
      47% of the centers. Despite the fact of 85% of the centers kept records with
      health information on the children, 93% of the centers did not have the required
      health license provided by the municipal authority. CONCLUSIONS: There is a good
      deal of work to do in both private and public day-care centers in order for them
      to comply with the current service regulations.

PMID- 14685602
TI  - [Protein/creatinine ratio in single urine samples for the semiquantitation of
      proteinuria in children with nephrosis]
AB  - OBJECTIVE: To estimate, semiquantitatively, the proteinuria of nephrotic patients
      by the use of the value of protein/creatinine ratio in single urine samples and
      determine its correlation with 24-hour proteinuria.METHODS: Analysis of 30 single
      urine samples and thirty 24-hour urine samples from 20 children with nephrosis
      followed up at the Division of Pediatric Nephrology of the University Hospital,
      Faculty of Medicine of Ribeirao Preto, University of Sao Paulo. Proteinuria in
      single urine samples and 24-hour urine samples was measured by the turbidimetric
      method with 3% sulfosalicylic acid. Urinary creatinine concentration was measured
      by the method of Hare, modified by Haugen and Blegen, adapted to the
      microtechnique.RESULTS: An excellent correlation was observed between 24-hour
      proteinuria and the protein/creatinine ratio in single urine samples, by linear
      regression analysis before (r = 0.82; p < 0.001) and after logarithmic
      transformation (r = 0.93; p < 0.001). All patients with 24-hour proteinuria at
      physiological levels (less than 0.1 g/m(2)/day) had a protein/creatinine ratio of
      less than 0.1 (mg/mg) in single urine samples. All patients with nephrotic 24
      hour proteinuria (more than 1.0 g/m(2)/day) had a protein/creatinine ratio of
      more than 1.0 (mg/mg). The patients with intermediate proteinuria (between 0.1
      and 1.0 g/m(2)/day) had a protein/creatinine ratio distributed on the three
      levels.CONCLUSIONS: The protein/creatinine ratio in a single urine sample is a
      simple and reliable method for the evaluation of proteinuria and eliminates the
      errors due to inadequate 24-hour urine collection.

PMID- 14685603
TI  - [Pneumothorax and pulmonary intersticial emphysema: treatment with selective
      bronchial occlusion and high frequency ventilation]
AB  - OBJECTIVE: Our purpose was to report the use of selective bronchial occlusion
      with a balloon catheter, associated with high frequency ventilation for a
      successful treatment of a persistent left hypertensive pneumothorax associated
      with left bronchopleural fistula and severe bilateral pulmonary intersticial
      emphysema.METHODS: A newborn infant of 20 hours of age was referred to our ICU
      for treatment of severe respiratory distress and hemodynamic failure after
      spontaneous hypertense left pneumothorax. Despite being submitted to conventional
      mechanical ventilation, volume resuscitation and vasoactive drugs infusion, the
      patient worsened. Therefore, he underwent selective occlusion of the main left
      bronchus, a measure that can be effective to interrupt gas flow to the affected
      lung in situations like lung injury with air leak. In order to avoid worsening
      intersticial emphysema and air leak, high frequency ventilation was associated.
      This method is characterized by very low tidal volume, lower than the rest
      functional capacity, and is indicated in acute respiratory failure associated
      with air leak syndrome.RESULTS: Selective left main bronchus occlusion and high
      frequency ventilation were successfully used to treat the patient who, after
      that, presented a favorable outcome with full hemodynamic and respiratory
      recovery.CONCLUSION: Selective left main bronchus occlusion permitted mechanical
      ventilation of the contralateral side and high frequency ventilation allowed
      adequate oxygenation and ventilation maintenance with decrease of the risk of
      lung injury and also allowed recovery from the interstitial emphysema.

PMID- 14685604
TI  - [Cisapride related movement disorders]
AB  - OBJECTIVE: To describe a case of movement disorder associated with cisapride use.
      METHOD: Case report.RESULTS: This is the case of a male eight months old child
      who began to use cisapride, 0,2 mg/kg tid to treat gastroesophageal reflux
      disease. One month after beginning with the drug, he started to present
      repetitive movements of the hands characterized by opening and closing hands with
      flexion and extension of the wrists. According to the mother, these movements
      became more evident as the dose of the medication was increased, and, thereafter,
      started to happen also on the feet. When the child was six months old, time of
      the first neurological evaluation, he presented normal neurological development,
      except for the Parachute reflex, which was absent. After excluding metabolic,
      toxic and infectious diseases, the drug was withdrew. The child evolution was
      benign, with gradual disappearance of the movements, and he was completely normal
      30 days after.CONCLUSIONS: The authors stress the need suspending the use of
      cisapride in any case of neurologic symptoms as seizures, somnolence, malaise or
      involuntary movements in previously normal patients.

PMID- 14685606
TI  - [Auto-PEEP in mechanical ventilation]

PMID- 14685605
TI  - [Ethic and legal dilemmas concerning critically ill patients]

PMID- 14685607
TI  - [Neonatal chronic lung disease]
AB  - OBJECTIVE: The author presents a review about neonatal chronic lung disease, with
      particular emphasis on pathophysiology and outpatient follow up. METHODS: The
      most relevant articles concerning the disorder were selected through Medline
      search, from the initial description of the disease, in 1967.RESULTS: Neonatal
      chronic lung disease is a condition with growing incidence due to progressive
      increase in survival of preterm infants. Neonatal chronic lung disease
      pathophysiology involves several factors, but prematurity and respiratory
      assistance to the newborn seem to play a major role in the pathogenic process.
      The treatment of neonatal chronic lung disease is complex and must be
      individualized. Diuretics, corticosteroids and bronchodilators are the most
      frequently used drugs, but their indication and timing for use remain
      controversial. Patient follow-up after hospital discharge is essential for a good
      prognosis, and must include nutritional and social aspects. CONCLUSIONS: Neonatal
      chronic lung disease is still a condition scarcely known among pediatricians,
      particularly regarding treatment after hospital discharge. Severe cases should be
      treated in specialized centers with advanced laboratory and management resources.
      The prognosis is remarkably variable and also related to the presence of other
      prematurity sequelae and prompt intervention on the complications.

PMID- 14685608
TI  - [Auto-PEEP effects on respiratory mechanics and blood gases in mechanically
      ventilated patients]
AB  - OBJECTIVE: The purpose of this study was to examine the auto-PEEP incidence and
      magnitude and the relationship between its reductions and changes in respiratory
      mechanics and gas exchanges in mechanically ventilated patients addmited in an
      Intensive Care Unit.METHODS: A prospective study was conducted in seventeen
      infants undergoing mechanical ventilation due to respiratory or neuromuscular
      diseases. We have measured blood gases, mean airway pressure, tidal volume,
      compliance, resistance and time constants of the respiratory system and monitored
      pressure, flow and volume waveforms and pressure-volume and flow-volume
      loops.RESULTS: Thirteen patients or 76% developed auto-PEEP and the reduction of
      its magnitude (from 5.4 -/+ 3.2 to 4.1 -/+ 2.6 cmH2O, p<0.01) showed association
      to mean airway pressure decrease (from 10.2 -/+ 3.1 to 9.3 -/+ 2.3 cmH2O,
      p<0.01), tidal volume (from 45.3 -/+ 19.1 to 51.3 -/+ 22.9 ml, p<0.01) and
      corrected compliance increase (1.02 -/+ 1.20 to 1.13 -/+ 1.41 ml/cmH2O/kg,
      p=0.05). Expiratory resistance remained unchanged (from 15.0 -/+ 8.6 to 15.7 -/+
      9.4 cmH2O/l/sec/kg, p=0.06). Arterial blood gases showed pH increase (from 7.37 
      /+ 0.12 to 7.42 -/+ 0.05, p<0.05) and PCO2 and PO2 decrease (from 40.1 -/+ 11.1
      mmHg to 33.1 -/+ 7.4 mmHg, p<0.01 and 65.0 -/+ 13.9 to 58.0 -/+ 12.6 mmHg, p<0.01
      respectively).CONCLUSIONS: Auto-PEEP reduction was associated with pulmonary
      mechanics and blood gases improvement. Knowledge of auto-PEEP presence and
      magnitude allowed to respiratory system compliance and time constants correction,
      providing accurate index of the pulmonary mechanics.

PMID- 14685609
TI  - [Preterm neonates treated in intensive care units: development of interaction
      behavior in the first year of life]
AB  - OBJECTIVE: The aim of this research was to characterize the interaction during
      the first year of preterm infants whose weight was lower than 2000g and who had
      been in neonatal intensive care units for at least 10 days. METHOD: Fifty-three
      infants were observed during a year, twenty-one being boys and thirty-two girls.
      These infants were assessed regarding seventeen kinds of behavior which we
      considered important in person to person relationship, i.e., behavior which led
      to interaction or maintained it. In our analysis we considered the age at which
      the child was seen, sex, weight at birth, new born classification, time of
      hospitalization and neurological diagnosis.RESULTS: An analysis of the results
      showed that there was an evolution in the way preterm infants interacted although
      the progress was smaller than the one of their pair terms. The occurrence of
      communicative behavior was not affected by sex, weight at birth or newborn
      classification (adequate or small for gestational age). The postnatal time of
      hospitalization affected the occurrence of the behavior smiles to the reflected
      image in mirror. The infants diagnosed as being neurologically impaired showed a
      statistically significant smaller occurrence of behaviors: respond to smiles and
      speech by smiling, play peek-a-boo, protest at mothers departure, point to
      desired objects and carry out given orders. CONCLUSIONS: The infants diagnosed as
      having neurological disabilities showed a delay in more complex forms of
      interaction. The infants with more than 35 days of hospitalization showed
      alteration in the self-body construction, related to personality build up.

PMID- 14685610
TI  - [Enteropathogens associated with acute diarrheal disease in children]
AB  - OBJECTIVE: Aiming a better understanding of the distribution of enteropathogens
      in Brazil, we have investigated the prevalence of enteropathogens in acute
      infantile diarrhea in children of low economic level from Sao Jose do Rio Preto,
      SP.METHODS: A prospective study with 196 children under age five, all with
      diarrhea, and 33 control subjects was conducted at Hospital de Base de Sao Jose
      do Rio Preto during 1995. This Hospital is associated to a Medicine School and
      offers free assistance to patients of low economic level who live in the area.
      RESULTS: Enteropathogens were identified in 48% of the cases and 27% of the
      controls. Shigella species were isolated in 21% of the cases, EPEC in 10.7%,
      Salmonella species in 5.6%. The other enteropathogens studied represented 12 % of
      the isolate pathogens from case children. In the controls 18.2% of atypical EPEC
      were isolated. Isolation of Shigella species increased with increasing age of
      cases and peaked in spring, whereas EPEC was common in early infancy and peaked
      in spring and winter.CONCLUSIONS: Among Sao Jose do Rio Preto children, Shigella
      species and diarrheiogenic E. coli strains (EPEC, ETEC, EAggEC, EIEC) were
      isolated throughout the year as a cause of diarrhea bringing children to a
      medical attention. Most of the pathogens were isolated in spring (mainly Shigella
      and Salmonella), so the temperature and humidity of the environment must be very
      important.

PMID- 14685611
TI  - [Prevalence of asthma in schoolchildren in Curitiba - ISAAC]
AB  - OBJECTIVE: To verify the prevalence of asthma in schoolchildren from
      Curitiba.METHOD: A written questionnaire of asthma symptoms (ISAAC-International
      Study of Asthma and Allergies in Childhood) was applied to children ages 6-7
      years and adolescents 13-14 years registered in 32 public schools.RESULTS: 3,200
      questionnaires were applied to 13-14 year-old adolescents, and 2,863
      questionnaires to 6-7 year-old children. The questionnaire should be answered by
      the parents of 6-7 year-old children (group I) and by the adolescents themselves
      (13-14 year-old, group II). The rate of questionnaires returned was 58% for group
      I and 92% for group II. A presumptive diagnosis of asthma was based on having had
      4 or more attacks of wheezing in the last 12 months, or 1-3 wheezing episodes in
      addition to night awakening for wheezing, nocturnal cough and wheezing after
      exercise. Under these criteria there were 15.7% asthmatics in group I and 11.6%
      in group II. Symptoms of rhinoconjunctivitis were found in 38% and 36%, and
      eczema in 11% and 10% for groups I and II, respectively. Among those with
      presumed asthma, over 70% denied having had asthma. The question "have you ever
      had asthma" although specific is not sensitive enough.CONCLUSION: The prevalence
      of asthma in Curitiba was 15.7% for children 6-7 years old and 11.6% for
      adolescents 13-14 years. The question "have you ever had asthma" did not
      contribute to defining cases with asthma.

PMID- 14685612
TI  - [Evaluation of the therapeutic efficacy of dexamethasone in meningococcal
      meningitis]
AB  - OBJECTIVE: To evaluate the efficacy of dexamethasone as an auxiliary therapeutic
      tool to the antibiotics in hospitalized children with meningococcal meningitis.
      METHODS: A retrospective clinical comparative study was undertaken with children
      from a pediatric ward affected by laboratory proved meningococcal meningitis at a
      university hospital. Cases of children in state of shock at admission or deceased
      in the first 24 hours were excluded. During the period from 1987 to 1989 33
      children were treated only with antibiotics (group A), while from 1990 to 1993
      other 66 children received additionally dexamethasone (12mg/m2/24h) by
      intravenous route during four days beginning at the admission to the hospital
      (group B). The two groups were evaluated at baseline through prognostic scores
      and analysis of their clinical and laboratorial characteristics obtained from
      data recorded at the admission. The parameters to evaluate dexamethasone efficacy
      were the comparative number of neurologic and systemic complications detected at
      the hospital, and the liquoric profile (leukocyte count, glucose and protein
      content) verified between day 9 and day 11 of hospitalization. RESULTS: The
      profile of the two groups (A and B) were homogeneously evaluated by the illness
      severity scores and their clinical and laboratorial characteristics. Nine
      complications were recognized in group A (27.2%) and 21 (31.8%) among those of
      group B, difference not significant. Likewise, there were not observed liquoric
      differences between the two groups related to the chimiocytologic pattern.
      CONCLUSIONS: No effect of dexamethasone therapy to prevent neurologic and
      systemic meningococcal meningitis complications was observed during
      hospitalization. Similarly no favorable effect in relation to the liquoric
      pattern verified between day 9 and day 11 of hospitalization was recognized.

PMID- 14685613
TI  - [Therapeutic of septic children with purpuric presentation with two antibiotic
      schedules]
AB  - OBJECTIVE: The authors evaluate the therapeutic efficacy of two antibiotic
      schedules, ceftriaxone alone and the combined use of ampicillin and
      chloramphenicol, in the treatment of septic children with purpuric
      presentation.METHODS: A randomized open clinical trial was conducted including
      septic children with purpuric presentation treated at a pediatric intensive care
      unit from April 1988 to June 1992. All cases with systemic purpura standing for
      less than a week were included in one of two groups, except for those recently
      hospitalized or with previous hemorrhagic disturbs. Patients in group A received
      ampicillin and chloramphenicol and those in group B were given ceftriaxone.
      Quantitative parameters were adopted to compare the efficacy of the two
      antibiotic schedules: sensitivity of bacteria isolated at blood and liquor
      cultures, complications, therapeutic procedures, period of hospitalization, and
      sequelae.RESULTS: 19 cases were included in the group A and 16 in group B, both
      homogenous on clinical-laboratorial aspects. The parameters evaluated did not
      show different efficacy between the two antimicrobial schedules tested, except
      for the number of complications observed during hospitalization, which was higher
      among the children that received ampicillin and chloramphenicol. The overall
      mortality for the patients treated was 13.8%, excluded the undernourished.
      CONCLUSIONS: The authors verify similar clinical therapeutic efficacy with the
      combined use of ampicillin and chloramphenicol or ceftriaxone, as observed
      previously. It must be pointed that the number of complications detected during
      hospitalization were higher in the group that received the combined antibiotic
      schedule. Low mortality in the present study may be attributed to the early
      diagnosis and therapeutic measures adopted at the pediatric intensive care unit.

PMID- 14685614
TI  - [Hepatitis C virus (HCV) in children and adolescent hemophiliacs]
AB  - OBJECTIVE: To evaluate the prevalence of infection by HCV among hemophiliacs in
      the State of Para (Brazil), and its possible relation to hepatic enzymes serum
      level, type of hemophilia involved, age, level of severity, kinds and
      combinations of treatment, as well as date in which treatment with hemoderivates
      was started.METHODS: Cross-sectional epidemiological investigation, analyzing 62
      hemophilic patients of the Centro de Hemoterapia do Para (HEMOPA), all born after
      01/01/80, by means of the review of the medical records, physical examination and
      laboratory tests: Anti-HCV (ELISA 3.0), polymerase chain reaction - PCR - (HCV
      RNA), and dosage of transaminases serum levels. Statistical analysis was carried
      out using Chi-square and Fisher's Exact Test, the results being considered
      significant if p</=0.05.RESULTS: Out of the 62 patients analyzed, 48.4% (n=30)
      were HCV positive. Among these patients, 43.3% (n=13) presented viraemia with
      detection of viral RNA using the PCR technique. HCV infection was related to the
      condition beginning of treatment before 1993 (p=0.0005); the type of hemophilia,
      being type A more frequent (p=0.028); the level of severity, with higher
      frequency in the moderate condition (p=0.026); and age, with higher frequency
      among those who were older than 5 years of age (p=0.025).CONCLUSION: Infection by
      HCV among hemophiliacs in the State of Para is high (48.4%) and was related to
      the beginning of the treatment before 1993, when obligatory serological trial for
      HCV was introduced in Brazilian blood banks. It is also significantly more
      frequent in children over five, with type A hemophilia of moderate gravity.

PMID- 14685615
TI  - [Asphyxiating thoracic dystrophy: a report of 3 cases]
AB  - OBJECTIVE: To drive pediatrician's attention to a syndrome wwich has as its
      typical clinical presentation a thoracic cage abnormality which evolves to
      respiratory distress and death during the first two years of life.METHODS: We
      describe three cases of patients with clinical and radiographic findings
      characteristic of asphyxiating thoracic dystrophy (Jeune's Syndrome): short and
      narrow thoracic cage and abnormal development of the ribs. A brief review of the
      literature on the subject is also included.RESULTS: The three patients are older
      then two years of age. They did not present life threatening pulmonary
      complication nor respiratory distress, in contrast to most of the cases reported
      in the literature.CONCLUSIONS: Even though the number of occurrences of this
      syndrome is quite low, it must be consider when conducting a differential
      diagnostic related to thoracic cage abnormalities. It is important to emphasize
      the degree of variability of the pulmonary lesions and the progress of the
      disease. However, most articles on the subject point to a grim outcome.

PMID- 14685617
TI  - [Breastfeeding and the use of human milk: what the American Academy of Pediatrics
      recommends]

PMID- 14685616
TI  - [Kaposiform hemangioendothelioma associated with Kasabach-Merritt syndrome]
AB  - OBJECTIVE: To describe a case of kaposiform hemangioendothelioma, the only
      malignant tumor of vascular origin specific of childhood.METHODS: We report a
      case of a 40-days-old girl who presented with a giant hemangioma of the face.
      Rapid enlargement of the tumor lead to laryngeal compression with severe
      respiratory distress. She had also a consumptive thrombocytopenic coagulopathy
      (Kasabach-Merritt syndrome).RESULTS: She was admitted to the pediatric intensive
      care unit of the Hospital das Clinicas da Universidade Estadual de Campinas and
      mechanical ventilation was introduced. A ten day course of dexamethasone was only
      partially effective. We then started alpha-2a interferon at a dose of 1.8 million
      units/m(2)/day by subcutaneous route, but she died four days after the onset of
      this therapy. The microscopic features showed a kaposiform
      hemangioendothelioma.CONCLUSION: We discuss this unusual fatal evolution of a
      rapidly growing hemangioma and its hematological complications.

PMID- 14685618
TI  - [Cardiopulmonar resuscitation - a challenge to premature death]

PMID- 14685619
TI  - [Paediatric life support: an advisory statement by the Pediatric Life Support
      Working Group of the International Liaison Committee on Resuscitation]

PMID- 14685620
TI  - [Aerosol therapy in childhood asthma]
AB  - OBJECTIVES: The aims of this review are to present research data about
      aerosoltherapy and to discuss the optimization of this form of drug
      administration.METHOD: Review of the literature, covering some of the most
      important studies about aerosoltherapy, inhaler devices, pharmacokinetics and
      pharmacodynamics of inhaled drugs.RESULTS: Factors that influence deposition
      pattern and pharmacokinetics of inhaled drugs are discussed, as well as how they
      can affect clinical efficacy. Positive and negative features of inhaler devices
      are compared; an attempt to establish dose equivalency of drug delivered by
      different devices is made.CONCLUSIONS: Different inhaler devices and different
      inhaling techniques produce different drug deposition patterns and clinical
      effects. So, those who deal with aerosoltherapy, including patients, must be well
      aware of all those issues, in order to achieve the best results.

PMID- 14685621
TI  - [Study of intrauterine growth of normal newborn infants]
AB  - OBJECTIVE: To evaluate the intrauterine normal growth profile and its variations.
      To draw an intrauterine growth standard at the maternity ward of Hospital
      Universitario Antonio Pedro (UFF-RJ) by studying the variables of weight, length,
      cephalic perimeter and ponderal index, at birth, from single foetus pregnancies.
      We compare those curves with those in other national research works, as well as
      with the classical one by Lubchenco.METHODS: The starting number of 1566 live
      births which happened between April, 1992 and September, 1993 was cut down to
      1031 due to exclusions resulting from interfering factors of foetus growth
      (Hypertensive Disease of Pregnancy, smoking mother, chronic arterial hypertension
      and major malformations). We also excluded from analysis those foetus of mothers
      who could not remember the date of their last period or when it was discordant in
      more than a week from Dubowtizs score.RESULTS: Comparing this standard of
      intrauterine growth to those chosen in literature, the present values were
      similar to other national curves that exclude intrauterine growth interfering
      factors. Comparing our curve with the classical Lubchencos curve, we observed
      higher mean values at lower gestational ages than the ones in Denvers study, and
      lower late desaceleration of the ponderal gain in the present one.The Ponderal
      Indexes of the present study have higher mean values compared to the ones in
      other studies, denoting, perhaps, higher prevalence of type I, or symmetric,
      intrauterine growth retard pattern.CONCLUSION: This study proposes a standard
      which is adequate to the assessment of intrauterine growth of similar
      populations.

PMID- 14685622
TI  - [Study of intestinal malabsorption diseases as cause of monosymptomatic short
      stature]
AB  - OBJECTIVE: This study was carried out in order to evaluate the etiology of
      monosymptomatic childhood short stature (below the third percentile or with
      growth rate of less than 5 cm/year) with emphasis on causes due to intestinal
      malabsorption. METHODS: Each patient was submitted to endocrinological,
      biochemical and hematological investigation. Determination of serum anti-gliadin
      antibodies, fecal fat, chloride levels in sweat, jejunal biopsy and bone age was
      also obtained.RESULTS: A total of 51 children was studied, most of them belonging
      to the group of normal variants. Four children had abnormally high sweat
      chloride, compatible with the diagnosis of cystic fibrosis. These children were
      asymptomatic regarding respiratory and gastrointestinal tract. CONCLUSIONS: We
      conclude that cystic fibrosis, besides celiac disease, must be included in the
      differential diagnosis of short stature in childhood.

PMID- 14685623
TI  - [Protein hydrolysate as a dietetic resource]
AB  - OBJECTIVE: The central goal of this paper was to study the application of beef
      meat and poultry (turkey and chicken) hydrolysates to the preparations used in
      our Brazilian current feeding practices. METHODS: The various kinds of meat were
      hydrolyzed with fresh pineapple under similar conditions to those daily used at
      home. The selection of three types of preparation was dependent on whether their
      contents included starch or gelatin and liquid, like soup, mousse and fruit
      shake. Hydrolysate were added to the preparations as part of the liquid content
      of their recipes. The acceptability of the preparations was checked out by
      employing the hedonic-scale affective test with untrained tasters. Variance
      analysis and the Tukeys test were performed with a 5% level of significance for
      the results.RESULTS: The selected recipes were the following: bitterroot soup,
      fruit and vegetable-shakes and grape mousse, all of them containing starch or
      gelatin as an element to camouflage the bitter taste of the aminoacids. The
      preparations were well accepted: approximately 76% of the tasters reported having
      liked the soup at least somewhat; as to the shakes, more than 50% gave positive
      answers, and as to the mousse, approximately 88% reported having liked it. There
      were no statistically significant differences (p< 0.05) concerning the
      application of the three hydrolysates in all the preparations tested.
      CONCLUSIONS: The use of hydrolysed meat to replace liquid content of recipes is
      highly practicable, requiring only an adequate selection of recipes and their
      ingredients, that should include starch and gelatin in order to get fully
      satisfactory products. These preparations might serve as a basis for other ones,
      adapted to each diet.

PMID- 14685624
TI  - [Clinical efficacy of four schemes for vivax malaria treatment in children]
AB  - OBJECTIVES: In the treatment of vivax malaria, an important factor affecting the
      occurrence of relapse is the duration of treatment. In Belem, a number of
      patients with vivax malaria were found to be cured despite failure to complete
      the standard course of treatment. In Belem, a number of patients with vivax
      malaria were found to be cured despite failure to complete the standard course of
      treatment. This observation suggested the present study, investigating more
      practicable courses of treatment for children with vivax malaria.METHODS: A
      randomized prospective clinical trial was conducted in 200 outpatient children
      with vivax malaria. Parasite clearance time and response to four therapeutic
      schedules were investigated: a) chloroquine*, 10 mg/kg in a single dose
      (chloroquine SD) + primaquine, 0.50 mg/kg/dose for 7 days; b) chloroquine SD +
      primaquine, 0.25 mg/kg/dose for 7 days; c) chloroquine SD + primaquine, 0.50
      mg/kg/dose for 5 days; d) chloroquine SD + primaquine, 0.25 mg/kg/dose for 5
      days. Fisherss Exact test was used to compare the responses to the
      schedules.RESULTS: All 144 children who completed the study had clearance of
      asexual parasitemia by the fourth day of treatment. Significant differences were
      observed between schedules A/D (p= 0.022) and C/D (p= 0.005). A doubled dose of
      primaquine (schedules A and C) proved to be significantly more effective
      (p=0.0042) than the standard dose (B and D). However, duration of treatment had
      no significant effect (p = 0.6104).CONCLUSIONS: In this study, complete cure of
      vivax malaria was better achieved with a doubled dose of primaquine than with
      standard doses. Effectiveness of the doubled dose was independent of the duration
      of treatment. Treatment schedule D is not recommended.

PMID- 14685627
TI  - [Congenital tuberculosis]
AB  - OBJECTIVE: Considering the rarity and the significance of early diagnosis for
      planning appropriate treatment, a case of congenital tuberculosis is
      reported.CASE REPORT: After a prolonged stay in the Neonatal Intensive Care Unit
      (NICU) of a male pre-term infant without improvement, the diagnosis of
      tuberculosis was suspected when his mother underwent thoracotomy for valve
      replacement due to a subacute endocarditis. At this time, multiple pleural
      granulomas were detected and the diagnosis of tuberculosis was confirmed by
      histology. His mother seldom went to the NICU to see the baby and she was rarely
      very close to him in these occasions. After tuberculosis therapy, the baby
      gradually improved. CONCLUSION: Among the possible ways of transmission, the
      reported case was probably transmitted by aspiration of contaminated amniotic
      fluid in utero or at the time of delivery.

PMID- 14685626
TI  - [Peptic disease: comparative study between children and adolescents]
AB  - OBJECTIVES: To make a comparative analysis of clinical and endoscopic data in
      peptic disease in a group of children (CR) and adolescents (AD).MATERIAL AND
      METHODS: 30 children and 76 adolescents with peptic disease were studied between
      August 1992 and November 1994. In all cases the diagnosis was confirmed by
      endoscopic and histologic examination. Clinical data referring abdominal pain
      (localization, degree of intensity, chronicity and related symptons) were
      compared in both groups. Statistical analysis was done by the Fisher Test
      (significance value p< 0.05).RESULTS: Findings referring to predominance in the
      female sex (66% in group CR versus 70% in group AD), duration of pain between 2
      and 6 months (40% CR versus 38% AD), intensive degree of pain (70% CR versus 83%
      AD) and presence of vomiting and nausea (42% CR versus 55% AD) were similar in
      both groups. Epigastric pain was predominant in AD (87%) versus CR (63%) with
      significant difference p=0.012. The endoscopic findings were normal in 30% of CR
      and 14% AD (p=0.052). Light to moderate gastritis was significantly more common
      in AD (72%) than CR (37%) (p=0.01). In the CR group, there was mainly antral
      nodular gastritis while in AD the diffuse form was more frequent. Bulbar
      duodenitis was present in 10% CR and 12% AD, but it was more erosive and serious
      in children. Peptic ulceration was found in 16% of CR (2 gastritis and 3
      duodenal) and 7% AD (1 gastric and 4 duodenal) (p=0.067). H. pylori colonization
      was more frequent in AD (52%) than in CR (36%) (p=0.195).CONCLUSIONS: 1)
      epigastric pain is the main symptom in both groups; 2) endoscopic findings may be
      normal especially in the childrens group; 3) antral nodular gastritis is the
      predominant type in children while in adolescents it is diffuse gastritis; 4) H.
      pylori colonization is present in 1/3 of children and 1/2 of adolescents with
      peptic disease; 5) in both groups ulcers are more frequent in the duodenum.

PMID- 14685628
TI  - [Anaphylatic reactions to ant stings]
AB  - OBJECTIVE: Relate the occurrence of severe anaphylactic reactions caused by ant
      stings.METHODS: Case report of severe anaphylactic reaction caused by multiple
      ant stings, and revision of the literature (Medline and Lilacs). RESULTS: A male
      patient, white, 2 years-old, suffered multiple stings of small red ants of the
      species Solenopsis invictas, with the occurrence of severe anaphylactic
      reactions, and resulting in cortical blindness as a neurological sequel.
      CONCLUSIONS: The occurrence of such events, not very rare, should be taken in
      consideration by physicians, once such insects are common in our environment, and
      their sting can result, sometimes, in severe anaphylactic reactions.

PMID- 14685629
TI  - [Pneumonia in the adult population in continental Portugal -- incidence and
      mortality in hospitalized patients from 1998 to 2000].
AB  - OBJECTIVE: To characterise the incidence and mortality in adult inpatients with
      community-acquired pneumonia at a global and regional level in mainland Portugal.
      PATIENTS AND METHODS: We used the clinical database belonging to the Ministry of
      Health's Instituto de Gestao e Informatica Financeira (Institute of Financial
      Management and Informatics), which contains the encoded information from the
      discharge letters from all hospitalisations at National Health Service
      institutions in mainland Portugal. We conducted a retrospective analysis of all
      hospitalisations in 1998, 1999 and 2000 with a main diagnosis of pneumonia on
      admission (ICD9: 480 to 486 and 487.0), excluding patients infected with the
      human immunodeficiency virus. RESULTS: From 1998 to 2000, hospitalisation of
      adults with pneumonia represented about 3% of the total number of admissions. We
      determined an average annual incidence of 2.66 hospitalisations for pneumonia per
      1,000 adult inhabitants and of 9.78 per 1,000 inhabitants aged > or =65. The
      average age of the adults interned was 70, with 71.6% of the patients aged > or
      =65. We believe that 25 to 50% of adults with community-acquired pneumonia are
      hospitalised. The mortality rate of adults hospitalised was 17.3%, with no
      significant difference between the sexes. Mortality rose to 21.5% and 24.8% in
      individuals aged > or =65 and > or =75, respectively. On average, 2.8% of the
      adults admitted were given mechanical ventilation and their mortality rate was
      43.9%. The incidence of hospitalisations for community-acquired pneumonia and its
      mortality differed from region to region in mainland Portugal. The annual
      incidence of admissions for pneumonia per 1,000 adult inhabitants in the central
      region was double that in the northern region and the Algarve and the mortality
      rate increased from north to south of the country, with a difference of more than
      50% in the Algarve in relation to the northern region. CONCLUSIONS: The incidence
      of hospitalisations for community-acquired pneumonia is comparable to the figures
      published in the international literature, though the hospital mortality rate is
      higher. We feel that it is essential to conduct more studies with a view to a
      more detailed characterisation of the situation in Portugal and a better
      understanding of the reasons for the discrepancies between the regions. This
      would possibly also enable us to implement measures to reduce the mortality rate.

PMID- 14685625
TI  - [Non-specific bronchoprovocation with metacholine in children before and during
      sugar cane burning in Catanduva-SP]
AB  - OBJECTIVE: Evaluate the influence of sugar cane burning on BHR of asthmatic and
      "normal" control children by metacholine bronchoprovocation tests; and verify if
      interferes in pulmonary function tests.METHODS: Twenty-two asthmatic children (A)
      aged from 7 to 14 years old, and twelve "normal" control children (C), aged from
      8 to 13 years, were submitted to non-specific bronchoprovocation test with
      methacholine before and during the sugar cane burning. The metacholine
      concentrations used were 0.025; 0.25; 1.0; 2.5; 10.0; 25.0 mg/ml, and the results
      were expressed in PC(20) FEV1 (concentration of metacholine that induces a fall
      of 20% or more in the forced expiratory volume in the first second).RESULTS: The
      PC(20) average for asthmatic children was significantly lower than the control
      group, before (A= 3.68; C= 25.62 mg/ml) and during the burning (A= 4.11; C= 25.25
      mg/ml) (p < 0.05). However, there were no significant differences, when compared
      in each group PC(20) values before and during burning. The same was observed
      regarding FEV1, forced vital capacity (FVC) and forced expiratory flux between 25
      and 75% of FVC (FEF (25-75%)).CONCLUSIONS: It was not possible to demonstrate
      that cane plantation burning influences the BHR, and pulmonary functions tests of
      the studied children.

PMID- 14685630
TI  - [Immigration and tuberculosis. Five year experience].
AB  - Immigrants are a tuberculosis risk group. In Portugal, in 2000, they had an
      incidence rate 3.6 times higher than the global incidence, and were native,
      predominantly, from Angola and Cabo Verde. Being the Chest Disease Center of
      Venda Nova located in a residential area with a great number of immigrants, most
      of them living in slums, we decided to evaluate the tuberculosis cases in this
      group, between 1996/2000, comparing the data obtained with some data of the
      tuberculosis cases in the non-immigrants. Immigrants with tuberculosis
      corresponded to 24.5% of all cases, 71.4% male, 93.9% black and mostly native
      from Cabo Verde and Angola. 73% lived in Portugal for more than 5 years, 86.7%
      were new cases and 13.3% relapses. 174 were pulmonary forms, 70.7% of which were
      D+ and 81% confirmed (against 75% in the non-immigrants). Of the 91 drug
      susceptibility tests done in the pulmonary forms, 9.9% revealed multidrug
      resistance, against 5% in the non-immigrants. Twenty six point six percent had
      AIDS against 18% in the non-immigrants. Some conclusions: important percentage of
      immigrants with tuberculosis in the Chest Disease Center of Venda Nova;
      immigrants have a higher confirmation rate of pulmonary tuberculosis, more
      multidrug resistance and AIDS cases.

PMID- 14685631
TI  - [Early discharge following major thoracic surgery: identification of related
      factors].
AB  - There is a direct relation between hospital costs and hospital length of stay
      after the operation. In the other hand, reduced stay increases the productivity
      of the public hospitals with high service demanding. The objective of this study
      was to identify factors determining the decrease in hospital stay after major
      thoracic surgery. A two-phase retrospective study was conducted on analysis of
      medical records. In the first phase, data on length of hospital stay and related
      factors were collected from a consecutive series of 169 patients divided into
      group I (n=81)--patients operated on between June 1990 and 1995, and group II
      (n=88)--1996 through May 2000. In the second phase, data were collected from a
      consecutive series of 20 patients (group III) starting backwards from March 2002,
      for analysis and comparison with a internet survey sent to 21 thoracic surgeons.
      Intensive care unit was avoided for most patients in the immediate post operative
      period. The mean hospital stay decreased from 7.6 days (median 7) in group I to
      5.1 days (median 4) in group II (p<0.001). The more frequent utilization of
      epidural analgesia and less traumatic thoracotomy in group II reached statistic
      significance (p<0.001). In group III, the mean hospital stay was 4.2 days (median
      4), and there was a more effective use of epidural analgesia (75%) and muscle
      sparing thoracotomy (90%). Eight thoracic surgeons answered the survey: the mean
      hospital stay varied from 5 to 9 days and all patients were sent to intensive
      care or similar units. Only two surgeons utilize muscle-sparing thoracotomy. This
      study confirms that pain control and less traumatic surgical approach are
      important for faster functional recovery of the patients. It suggests that the IC
      units may be used only for selected patients.

PMID- 14685632
TI  - [Sequential chemo-radiation in non-small cell lung cancer: a retrospective study
      of 100 patients].
AB  - Combined chemotherapy and radiotherapy has shown to be the correct treatment of
      unresectable non-small cell lung cancer, after many years of poor survival
      figures with standard radiotherapy alone. It has also been demonstrated that the
      benefit of chemotherapy is mainly achieved if cisplatin-based schedules are used.
      The authors present a retrospective study of 100 cases of stage III non-small
      cell lung cancer treated with a sequential approach of chemotherapy and
      radiotherapy and evaluate median and overall survival, local progression-free
      survival and distant progression-free survival. The results of our series are
      quite similar to those published in literature.

PMID- 14685633
TI  - [Lung cancer and women].
AB  - The epidemiology of lung cancer has changed in the last years in several
      countries all over the world. In the 19th century, the lung cancer was rare but
      it incidence increase drastically during the 20th century, and the tendency is to
      continue in the 20th century. Actually the lung cancer's incidence and mortality
      are higher in the developed countries, especially in Europe and Unites States of
      America, with a increasing in the women incidence. These geographic differences
      and gender differences are related with smoking habits. Women begin to smoke
      earlier and have more difficulty to stop, because of problems related with
      obesity; they have more sensibility to the carcinogens and the risk of lung
      cancer is 1.5 times higher than the men with the same habits. Adenocarcinoma is
      the more frequent histological type in young people, in the total of the women
      and in non-smokers. Many factors since tobacco, home and professional pollution,
      nutritional, associated diseases even genetic and hormonal factors have been
      investigated to define its influence in development in women lung cancer. It
      specificity in women with lung cancer is the common problem for the medical
      people to treat this disease (pathology).The literature about this problem is not
      clear, and is necessary to advance with many studies in this area with the
      objective to clarify this important question.

PMID- 14685634
TI  - [Congenital cystic adenomatoid malformation of the lung or congenital pulmonary
      airway malformation].
AB  - The cystic adenomatoid malformation of the lung is an hamartomatous lesion,
      easily identifiable by its morphology through the application of Stocker's et al
      (1977) classification (type 1, 2 and 3) and also following the criteria of
      Yousem, to understand the five types dependent on the level of malformation in
      the airway and lung. The three morphological types described by Stocker were
      identified in 6 cases of the archive of the Department of Pathology of Coimbra's
      University Hospital, studied morphologically by the use of Movat's pentachromic
      stain and the application of the antibody anti-CK7 and anti-body anti-TTF1. In
      the three morphological types the elastic alveolar net is absent. The CK7
      identifies the epithelial distribution and is useful to evaluate the extension of
      the inflammatory lesion. The antibody anti-TTF1, apparently absent in type 3
      cases, is easily identified in type 1 and 2 cases and overexpressed in
      inflammatory areas. It seems that the absence of cells identified by the antibody
      anti-TTF1 prevents overdiagnosing of type 4 in Yousem's classification of
      congenital pulmonary airway malformation (CPAM).

PMID- 14685635
TI  - [The cost of tuberculosis care: in-patient estimated costs].
AB  - OBJECTIVE: To calculate the costs of in hospital tuberculosis treatment and to
      compare the estimated charges of multidrug-resistant tuberculosis (MDR-TB) and
      drug susceptible tuberculosis patients (TB). DESIGN: Descriptive study. SETTING:
      Tuberculosis Unit (Pulido Valente Hospital), Lisbon, Portugal. METHODS: The
      records of all TB patients discharged between January and December 2000 were
      reviewed. The cost analysis was conducted by using the hospital cost accounting
      system data and the charges approved by the national public health system. The
      main outcome measures were the following costs: 1) laboratory and ancillary
      services, 2) medication and 3) other direct and indirect components. RESULTS: The
      116 study patients were divided into 3 groups: HIV/TB-48 (41.4%), TB 62 (53.4%)
      and MDR-TB-6 (5.2%). The estimated cost of treatment for all patients was PTE
      213,732.769, but only 42% was covered by diagnosis-related groups financing
      system. In the MDR-TB group, the median cost per day (PTE 7,531) and the median
      cost per episode (PTE 316,593) were significantly higher comparing with the TB
      group, regarding laboratory services and medication items. CONCLUSIONS: The
      hospital care budget based on the diagnosis-related groups financing system,
      accounted for less than half the estimated costs of tuberculosis in-patients.
      Also, in regarding tuberculosis the diagnosis-related groups system does not
      account for a major confounder like MDR-TB, which has an huge impact on the
      length of hospital stay and increasing laboratory and medication costs.

PMID- 14685636
TI  - [Endocrine and metabolic expression in bronchogenic carcinoma].
AB  - In the present paper, the authors reviews the endocrine and metabolic
      manifestations in bronchogenic carcinoma. Disorders as paraneoplastic syndromes
      (hypercalcemia, syndrome of inappropriate antidiuretic hormone, carcinoid and
      Cushing's syndromes) and others endocrinopathies are discussed. Hypertrophic
      pulmonary osteoarthropathy is briefly reviewed.

PMID- 14685637
TI  - [Anemia associated with malignancy].
AB  - In this paper the authors reviews the anaemia in cancer patients, its mechanisms,
      diagnosis, and therapeutics, especially the indications for blood transfusion and
      the use of recombinant human erythropoietin. Also, the author reviews the impact
      of anaemia in quality of life and in the outcome of therapy and of cancer itself.

PMID- 14685638
TI  - [Pulmonary embolism diagnosis].
AB  - Pulmonary Embolism is often considered a difficult diagnosis to establish. It is
      important to recognise clinical situations that leads to it. There are a few
      laboratory and imaging tests, that should be tailored to the available facilities
      in each institution.

PMID- 14685639
TI  - [Bronchoalveolar lavage in HIV patients].
AB  - Lung is the preferential target organ of diseases associated with
      immunodeficiency virus infection. Taking into consideration that fiberoptic
      bronchoscopy (FB) with collection of bronchoalveolar lavage fluid (BAL) is a
      procedure of the highest utility for the etiological clarification of the
      pulmonary complications in AIDS patients, the authors carried out a review of the
      most frequent pathologies in this context and present the most frequent
      indications for FB with BAL. They also compare the results obtained in an
      American hospital and in two Portuguese ones.

PMID- 14685640
TI  - [Morphological features of the pulmonary sequestration].
AB  - The pulmonary sequestration corresponds to pulmonary tissue intra or extra-lobar
      with systemic arterial nutrition and collateral bronchial ramification. It is
      infrequent and the intra-lobar identification depends on the correct clinical
      signs and morphology. The correct study includes imagiologic identification of
      the systemic artery and morphological characterization of parenchymal changes.
      These allow identification of abnormal pulmonary parenchyma in intra-lobar cases
      and were observed using histochemical and immunohistochemical routine methods,
      both in intra and extra-lobar cases. Four cases of intra-lobar sequestration and
      four cases of extra-lobar sequestration were studied with application of
      histochemical techniques--Movat's pentachrome stain and Verhoeff--and
      immunolabelling with CK7 and TTF1. The parenchymal inflammatory distortion by
      collagenization was constantly seen as was BALT hyperplasia and pleuritis. By
      using Movat's pentachrome stain we characterized the sequestration by identifying
      the artery and the parenchymal changes. The CK7 was useful in the identification
      of parenchymal damage, together with the antibody anti-TTF1 that had a variable
      expression, stronger in areas of inflammation because of PII hyperplasia.

PMID- 14685641
TI  - [Lung abscess in infancy--a rare disease. Clinical cases].
AB  - Lung abscess is a rare entity in childhood, but leads to high morbidity and long
      length of hospitalisation. It appears commonly in children with risk factors or
      other disease, have a good response to antibiotic therapy and it is rarely
      necessary the use of invasive techniques. Authors present two cases of lung
      abscess in children, one of them with risk factors to aspiration, that improved
      with antibiotic therapy and make a revision about this entity in infancy.

PMID- 14685642
TI  - [Paracoccidiodomycosis, disseminated chronic form--case report].
AB  - Case report of paracoccidiodomycosis Chronic Form, adult type, with genital
      lesions and residual form presented as dysphagia and dysphonia at the same
      patient. Diagnosis accomplished by direct examination of clinical specimens, in
      this case cutaneous lesions. After specific treatment there was regression of
      lesions and symptoms had disappeared.

PMID- 14685643
TI  - Estradiol and testosterone modulate the anesthetic action of the GABA-A agonist
      THIP, but not of the neurosteroid 3alpha,5beta-pregnanolone in the rat.
AB  - RATIONALE: As sex steroids modify the number and distribution of brain gamma
      aminobutyric acid (GABA)A receptor subunits, we investigated the potential
      modulation of anesthesia, induced by agents acting on the GABAA receptor, by
      estrogen and androgen. OBJECTIVES: To assess possible effects of sex and hormonal
      condition (i.e., intact vs castrate; estradiol vs testosterone treatment) on the
      anesthetic effect of a GABAA agonist, THIP (4,5,6,7-tetrahydroisoxazolo[5,4,
      c]pyridin-3-ol hydrochloride), and an allosteric modulator of the GABAA receptor:
      3alpha-hydroxy-5beta-pregnan-20-one (epipregnanolone). METHODS: The potencies of
      THIP and epipregnanolone for inducing loss of the righting response were compared
      between: (a) female and male rats; (b) intact and castrated animals of each sex;
      (c) untreated castrates and castrates given estradiol or testosterone. RESULTS:
      Sex and endocrine condition influenced sensitivity to i.v. THIP for the induction
      of anesthesia. ED50 values were: gonadectomized females, 80 mg/kg>intact males,
      50 mg/kg>proestrous females, 35 mg/kg>gonadectomized males, 28 mg/kg. Estradiol
      benzoate (EB; 3 microg/day for 5 days) significantly increased THIP sensitivity
      in gonadectomized females: THIP+EB: ED50=26 mg/kg vs THIP+sesame oil: ED50=94
      mg/kg, while testosterone propionate (TP; 10 mg injected 24 h before THIP)
      decreased THIP sensitivity in orchidectomized males when compared with vehicle
      injected animals (ED50=72 mg/kg vs 22 mg/kg, respectively). CONCLUSIONS: Results
      suggest that estrogen increases the density or availability of GABAA receptor
      subtypes on which THIP acts, while testosterone exerts the opposite effect.
      Neither sex nor gonadal condition influenced the anesthetic action of
      epipregnanolone as a similar potency was found in intact and in gonadectomized
      males and females.

PMID- 14685645
TI  - Prediction of the response to citalopram and reboxetine in post-stroke depressed
      patients.
AB  - RATIONALE AND OBJECTIVE: Depression is a significant complication of stroke. The
      effectiveness of antidepressant drugs in the management of post-stroke depression
      (PSD) has been widely investigated. However, the choice of antidepressant drug is
      critically influenced by its safety and tolerability and by its effect on
      concurrent pathologies. Here we investigate the efficacy and safety of a
      selective serotonin reuptake inhibitor (SSRI), citalopram, and a noradrenaline
      reuptake inhibitor (NARI), reboxetine, in post-stroke patients affected by
      anxious depression or retarded depression. METHODS: This was a randomized double
      blind study. Seventy-four post-stroke depressed patients were diagnosed as
      affected by anxious or retarded depression by using a synoptic table.
      Randomisation was planned so that 50% of the patients in each subgroup were
      assigned for 16 weeks to treatment with citalopram and the remaining 50% were
      assigned to treatment with reboxetine. The Beck Depression Inventory (BDI), the
      Hamilton Depression Rating Scale (HDRS) and a synoptic table were used to score
      depressive symptoms. RESULTS: Both citalopram and reboxetine showed good safety
      and tolerability. Citalopram exhibited greater efficacy in anxious depressed
      patients, while reboxetine was more effective in retarded depressed patients.
      CONCLUSIONS: Citalopram or other SSRIs and reboxetine may be of first choice
      treatment in PSD because of their good efficacy and lack of severe side effects.
      In addition, PSD patients should be classified according to their clinical
      profile (similarly to patients affected by primary depression) for the selection
      of SSRIs or reboxetine as drugs of choice in particular subgroups of patients.

PMID- 14685644
TI  - Selective remodeling of rabbit frontal cortex: relationship between 5-HT2A
      receptor density and associative learning.
AB  - RATIONALE: Associative learning during classical trace eyeblink conditioning has
      been shown to be regulated by serotonin 5-HT(2A )receptors and to be critically
      dependent on the integrity of frontal cortex. Chronic administration of 5-HT(2A)
      ligands has been shown to produce a selective up- or down-regulation of 5-HT(2A)
      receptors in frontal cortex. OBJECTIVES: We examined whether alterations in 5
      HT(2A) receptor density had a functional significance with respect to associative
      learning. METHODS: Animals received chronic injections of LSD, BOL or MDL11,939
      and 1 day later began classical trace conditioning of the eyeblink response.
      RESULTS: The density of 5-HT(2A) receptors in frontal cortex was significantly
      increased at 1-4 days after the cessation of chronic injections of the selective
      5-HT(2A) receptor ligand MDL11,939. Rabbits demonstrated an enhancement of
      associative learning when training began at 1 day after cessation of chronic
      MDL11,939 injections, but acquired at the same rate as controls when training
      began at 8 days after cessation of injections, a time when receptor density had
      returned to control levels. Animals that began training 1 day after chronic
      injections of BOL or LSD, drugs that produce decreases in 5-HT(2A) receptor
      density, demonstrated normal rates of acquisition. CONCLUSIONS: These results
      indicate that increases in the density of 5-HT(2A) receptors in frontal cortex
      are associated with increases in the rate of associative learning, and further
      support an important role for this receptor in cortical circuitry that mediates
      learning. More generally, these results suggest an approach for functional
      remodeling of brain regions in the adult animal.

PMID- 14685646
TI  - Nicorandil attenuates the mitochondrial Ca2+ overload with accompanying
      depolarization of the mitochondrial membrane in the heart.
AB  - The anti-anginal drug nicorandil has been demonstrated to protect the myocardium
      against ischemic injury in both experimental and clinical studies. Although
      nicorandil seems to protect the myocardium via activation of mitochondrial ATP
      sensitive K+ (mitoKATP) channels, the mechanisms underlying its cardioprotection
      have remained elusive. We therefore examined whether nicorandil depolarizes the
      mitochondrial membrane and attenuates the mitochondrial Ca2+ overload. With the
      use of a Nipkow confocal system, the mitochondrial Ca2+ concentration ([Ca2+]m)
      and the mitochondrial membrane potential (DeltaPsim) in rat ventricular myocytes
      were measured by loading cells with rhod-2 and JC-1 respectively. The number of
      cell hypercontractures resulting from mitochondrial Ca2+ overload was counted.
      Exposing cells to ouabain (1 mM) evoked mitochondrial Ca2+ overload and increased
      the intensity of rhod-2 fluorescence to 180+/-15% of baseline ( p<0.001).
      Nicorandil (100 microM) significantly attenuated the ouabain-induced
      mitochondrial Ca2+ overload (129+/-4% of baseline; p<0.001 vs. ouabain).
      Nicorandil decreased the DeltaPsim during application of ouabain, thereby
      reducing the intensity of JC-1 fluorescence to 89+/-2% of baseline ( p<0.05).
      Exposure of myocytes to ouabain eventually resulted in cell hypercontracture
      (51+/-2%). This ouabain-induced cell hypercontracture was blunted by application
      of nicorandil (37+/-2%, p<0.05 vs. ouabain). Moreover, these effects of
      nicorandil were abolished by 5-hydroxydecanoate (500 microM), a putative mitoKATP
      channel blocker, and by glibenclamide (10 microM), a nonselective KATP channel
      blocker. Our results suggest that nicorandil attenuates the matrix Ca2+ overload
      with accompanying depolarization of the mitochondrial membrane. Such effect might
      potentially be attributed to the mechanism of cardioprotection afforded by
      nicorandil.

PMID- 14685647
TI  - Low glutathione S-transferase dogs.
AB  - Liver and kidney glutathione S-transferase (GST) activities to 1,2-dichloro-4
      nitrobenzene (DCNB) as a substrate (GST-D activities) were measured in 280 dogs
      from five different breeders, and significant individual differences in this
      activity were observed in both organs. Interestingly, 34 out of the 280 dogs
      (i.e. 12.1%) were those in which liver GST-D activities were less than 10
      nmol/min per mg cytosolic protein, "low GST dogs", and the other dogs were
      classified as "middle" and "high" GST dogs for which the liver GST-D activities
      were 10-80 and >80 nmol/min per mg protein, respectively, and occurred at similar
      percentages (41.4% for the middle GST dog and 46.4% for the high GST dog).
      Furthermore, the existence of the low GST dogs was not limited to one particular
      breeder. There was a good correlation (r=0.910) between the liver and kidney GST
      D activities, showing low activity in not only the liver but also the kidney in
      the low GST dogs. Although liver GST activity to 1-chloro-2,4-dinitrobenzene as a
      substrate (GST-C activity), catalyzed by various GST isozymes in dogs, was
      significantly correlated with liver GST-D activity, GST-C activity showed more
      than 450 nmol/min per mg protein even in the low GST dogs. There was no
      significant difference in cytochrome P450 content, 7-ethoxycoumarin O-deethylase
      activity or UDP-glucuronosyltransferase activity to p-nitrophenol as a substrate
      between low GST dogs and the other dogs. Finally, remarkably high plasma
      concentrations of DCNB were observed in the low GST dogs after single doses of
      DCNB at 5 or 100 mg/kg. The individual differences in GST-D activity are probably
      attributable to the content and/or activity of the theta class GST isozyme
      Yd(f)Yd(f) since it has been reported that glutathione conjugation of DCNB is
      specifically catalyzed by GSTYd(f)Yd(f) in dogs. In conclusion, we identified a
      number of low GST dogs in which the GST-D activities were not observed either in
      vivo or in vitro. The feasibility of using a single low dose of DCNB to phenotype
      dogs based on GST-D activity was confirmed. It was also suggested that low GST
      dogs have high susceptibility, including unexpected toxicity or abnormal
      exposure, to chemicals metabolized by GSTYd(f)Yd(f).

PMID- 14685648
TI  - Ethiopian soils harbor natural populations of rhizobia that form symbioses with
      common bean ( Phaseolus vulgaris L.).
AB  - The diversity and taxonomic relationships of 83 bean-nodulating rhizobia
      indigenous to Ethiopian soils were characterized by PCR-RFLP of the internally
      transcribed spacer (ITS) region between the 16S and 23S rRNA genes, 16S rRNA gene
      sequence analysis, multilocus enzyme electrophoresis (MLEE), and amplified
      fragment-length polymorphism. The isolates fell into 13 distinct genotypes
      according to PCR-RFLP analysis of the ITS region. Based on MLEE, the majority of
      these genotypes (70%) was genetically related to the type strain of Rhizobium
      leguminosarum. However, from analysis of their 16S rRNA genes, the majority was
      placed with Rhizobium etli. Transfer and recombination of the 16S rRNA gene from
      presumptively introduced R. etli to local R. leguminosarum is a possible theory
      to explain these contrasting results. However, it seems unlikely that bean
      rhizobia originating from the Americas (or Europe) extensively colonized soils of
      Ethiopia because Rhizobium tropici, Rhizobium gallicum, and Rhizobium giardinii
      were not detected and only a single ineffective isolate of R. etli that
      originated from a remote location was identified. Therefore, Ethiopian R.
      leguminosarum may have acquired the determinants for nodulation of bean from a
      low number of introduced bean-nodulating rhizobia that either are poor
      competitors for nodulation of bean or that failed to survive in the Ethiopian
      environment. Furthermore, it may be concluded from the genetic data presented
      here that the evidence for separating R. leguminosarum and R. etli into two
      separate species is inconclusive.

PMID- 14685649
TI  - Escherichia coli RNase E and RNase G cleave a Bacillus subtilis transcript at the
      same site in a structure-dependent manner.
AB  - The decay of Bacillus subtilis aprE leader- lacZ mRNA was examined in Escherichia
      coli wild-type and in mutants deficient in RNase E, RNase G, or both. Two
      versions of the mRNA were studied: the wild-type mRNA, which has a stem-loop at
      the 5' end, and a mutant mRNA, with a single-stranded 5' end. The half-life of
      both transcripts was determined by RNase E, the half-life of the mutant
      transcript being one-third of that of the wild-type transcript. RNase G cleaved
      both transcripts at a site within an AU-rich sequence in the stem-loop region,
      but cleavage was much more efficient when the stem-loop was destabilized. RNase E
      cleaved at the same site, but less efficiently and only in the mutant transcript.

PMID- 14685650
TI  - The relationship between social deprivation, osteoporosis, and falls.
AB  - The aim of this study was to assess the relationship between heel BMD, risk
      factors for osteoporosis, falls history, and the Jarman Underprivileged Area
      Score in an older community population. From the general practice register, 1,187
      women (mean age 70, range 60 to 94) were recruited. BMD of the heel was measured
      using the GE Lunar PIXI densitometer. A T-score cutoff for predicted osteoporosis
      at the spine or hip of -1.7 was used. A risk factor questionnaire was completed
      that included fracture history and falls history. The odds ratio (OR) with a 95%
      confidence interval (CI) was calculated for each risk factor for each quartile of
      Jarman score and for the diagnosis of osteoporosis. Logistic regression was used
      to identify the risk factors that predict lone bone mass in the heel. There were
      no significant differences between women in different quartiles of Jarman score
      in terms of age and body mass index (BMI). Women in the highest two quartiles of
      Jarman score (i.e., most deprived) had a significantly higher likelihood of
      osteoporosis (OR=1.82; 95% CI, 1.03 to 1.63; and OR=1.85; 95% CI, 1.04 to 1.64,
      respectively) and significantly lower BMD ( p=0.008). Women in these two
      quartiles were significantly more likely to have had a history of previous
      fracture (OR=1.66; 95% CI, 1.01 to 1.53), but there was no difference in falls
      history. Women in the lowest quartile (least deprived) were also significantly
      less likely to smoke ( p=0.011) but were not significantly different in terms of
      other risk factors (e.g., dietary calcium and activity). BMI, age, kyphosis,
      significant visual problems, and quartile of Jarman score were significant risk
      factors for low bone mass. Risk factors identified those with low bone mass at
      the heel with a sensitivity and specificity of 72%. In conclusion, women in the
      lowest quartile of Jarman score (i.e., least deprived) have significantly higher
      heel BMD compared with the rest of the population.

PMID- 14685651
TI  - Birth weight and musculoskeletal health in 36-year-old men and women: results
      from the Amsterdam Growth and Health Longitudinal Study.
AB  - The results of recent epidemiological studies suggest that birth weight is
      related to adult bone mineral status. Since birth weight might also be related to
      muscle strength and fat-free mass, which are important determinants of bone
      health, the aim of this study was to investigate the following: is birth weight
      related to bone mineral content (BMC) and bone mineral density (BMD) at the
      lumbar level, at the hip and of the total body, and to structural properties of
      the heel bone, to fat-free mass (FFM) and to muscle strength, at the age of 36
      years? Two hundred and eighty-two subjects (162 women) underwent dual X-ray
      absorptiometry (DEXA) measurement for the assessment of BMC and BMD at different
      sites and the FFM and/or measurement of the structural properties of the heel
      bone, which were estimated with speed of sound (H-SOS) and broadband ultrasound
      attenuation. Muscle strength was assessed with two fitness tests (static arm
      pull, and high jump). Information on birth weight was gathered by means of a
      questionnaire. The data were analyzed by application of multiple linear
      regression. Birth weight was positively related to FFM. In a crude model, birth
      weight was found to be positively associated with BMC, but not after adjustment
      for adult body weight. No significant associations were found between birth
      weight and muscle strength or birth weight and BMD. Furthermore, birth weight was
      inversely related to H-SOS. No other relationships were observed. Results support
      the fetal origins hypothesis that lower birth weight is related to lower BMC and
      FFM, but not that birth weight is associated with BMD and muscle strength.
      Furthermore, FFM was not identified as a link between birth weight and
      musculoskeletal health.

PMID- 14685652
TI  - Can the WHO definition of osteoporosis be applied to multi-site axial
      transmission quantitative ultrasound?
AB  - Osteoporosis is a highly prevalent but preventable disease and, as such, it is
      important that there are appropriate diagnostic criteria to identify those at
      risk of low trauma fracture. In 1994 the World Health Organization (WHO)
      introduced definitions of osteoporosis and osteopenia using T-scores, which
      identified 30% of all Caucasian post-menopausal women as having osteoporosis.
      However, the use of the WHO T-score thresholds of -2.5 for osteoporosis and -1.0
      for osteopenia may be inappropriate at skeletal sites other than the spine, hip
      and forearm or when other modalities, such as quantitative ultrasound (QUS) are
      used. The aim of this study was to evaluate the age-dependence of T-scores for
      speed of sound (SOS) measurements at the radius, tibia, phalanx and metatarsal by
      use of the Sunlight Omnisense, to evaluate the prevalence of osteoporosis and
      osteopenia at these sites by use of the WHO criteria, and calculate appropriate
      equivalent T-score thresholds. The study population consisted of 278 healthy pre
      menopausal women, 194 healthy post-menopausal women and 115 women with atraumatic
      vertebral fractures. All women had SOS measurements at the radius, tibia, phalanx
      and metatarsal and bone mineral density (BMD) measurements at the lumbar spine
      and hip. A group of healthy pre-menopausal women aged 20-40 years from the pre
      menopausal group were used to estimate the population mean and SD for each of the
      SOS and BMD measurement sites. Healthy post-menopausal women were classified into
      normal, osteopenic or osteoporotic, based upon the standard WHO definition of
      osteoporosis and expressed as a percentage. We investigated the age-related
      decline in T-scores from 20-79 by stratifying the healthy subjects into 10-year
      age groups and calculating the mean T-score for each of these groups. Finally, we
      estimated appropriate T-score thresholds, using five different approaches. The
      prevalence of osteoporosis in the post-menopausal women aged 50 years and over
      ranged from 1.4 to 12.7% for SOS and 1.3 to 5.2% for BMD. The age-related decline
      in T-scores ranged from -0.92 to -1.80 for SOS measurements in the 60 to 69-year
      age group and -0.60 to -1.19 for BMD measurements in the same age group. The WHO
      definition was not suitable for use with SOS measurements, and revised T-score
      thresholds for the diagnosis of osteoporosis of -2.6, -3.0, -3.0 and -2.2 and for
      osteopenia of -1.4, -1.6, -2.3, and -1.4, for the radius, tibia, phalanx and
      metatarsal, respectively, were recommended.

PMID- 14685653
TI  - Intravenous immunoglobulins and transplantation for patients with anti-HLA
      antibodies.
AB  - Transplantation for patients possessing allo-antibodies against HLA antigens can
      be delayed for years, and, once the graft has been transplanted, its survival is
      significantly reduced. We and others have shown that administration of
      intravenous immunoglobulins (IVIgs) can induce a profound and sustained decrease
      in the titres of the anti-HLA antibodies, thus greatly enhancing the chances of
      those patients to obtain a transplant. In a number of cases, pre-treatment sera
      contained anti-donor antibodies that disappeared after IVIg administration. A
      similar approach, combining plasmapheresis and low-dose IVIgs, has shown similar
      results and has been successfully applied to ABO-incompatible transplantations.
      Patient and graft survival are excellent, despite a rather high rate of
      rejections, most notably humoral ones. These protocols thus demonstrate that the
      presence of anti-donor antibody, once an absolute contra-indication to
      transplantation, can, nowadays, be considered as an immunological hurdle that can
      be managed through appropriate immunological manipulation.

PMID- 14685654
TI  - A waiver of consent for intensive care research?

PMID- 14685655
TI  - To consent or not to consent, that is (not) the (sole) question. "And there is
      nothing new under the sun". Kohelet (also known as Ecclesiastes), 1:9. Bible.

PMID- 14685657
TI  - Ultrasound of the lung: just imagine.

PMID- 14685656
TI  - A puzzling electrocardiogram.

PMID- 14685658
TI  - A novel expiratory circuit for recovery of perfluorocarbon liquid during partial
      liquid ventilation.
AB  - OBJECTIVE: To determine whether perfluorocarbon liquid can be condensed from
      gases containing perfluorocarbon vapour and whether the amount recovered varies
      with background flow rate. DESIGN AND SETTING: Bench-top experimental study in a
      neonatal laboratory. INTERVENTIONS: The expiratory limb of a standard ventilator
      circuit set-up was mimicked, with the addition of a chilled water jacket (Liebig)
      condenser. Perfluorocarbon vapour was passed through the circuit at a number of
      flow rates. MEASUREMENTS AND RESULTS: Perfluorocarbon vapour was passed through
      the circuit and the percentage recovery of liquid measured. More than 60% of the
      perfluorocarbon vapour was recovered at all flow rates (1, 2, 5 and 10 l/min),
      with significantly higher recovery obtained (up to 74%) at low flow rates (1
      l/min). CONCLUSIONS: Using a simple condenser, more than 60% of perfluorocarbon
      liquid can be recovered without altering the function of an expiratory limb of a
      ventilator circuit.

PMID- 14685659
TI  - Unexplained metabolic acidosis in critically ill patients: the role of
      pyroglutamic acid.
AB  - OBJECTIVE: To determine the role of pyroglutamic acid (PGA) in the pathogenesis
      of unexplained metabolic acidosis in critically ill patients. DESIGN AND SETTING:
      Case series in the medical ICU of an urban hospital. PATIENTS: 23 patients
      admitted to the medical ICU with acidemia (pH <7.35 or HC0(3) < or = 16 mEq/l)
      not explained by the presence of ketoacidosis, lactic acidosis, renal failure or
      ingestion of drugs or toxins and who had an increase in the strong ion gap (SIG)
      greater than 5. MEASUREMENTS AND RESULTS: Plasma levels of sodium, potassium,
      chloride, bicarbonate, calcium (ionized), magnesium, lactate, phosphate, albumin,
      blood urea nitrogen, and creatinine were measured. Arterial blood gases and urine
      dipstick for ketones were also analyzed. Plasma was assayed for PGA using gas
      chromatography. The patient's history and Kardex were reviewed for evidence of
      acetaminophen administration. The plasma PGA level was found to be very low in
      all patients studied. The correlation between SIG and PGA (r) was -0.01 (95% CI: 
      0.42 to 0.40). PGA therefore did not account for the observed increase in the
      SIG. There appeared to be no obvious influence of acetaminophen intake on levels
      of PGA in the plasma. CONCLUSIONS: We were unable to confirm the importance of
      PGA as a cause of unexplained metabolic acidosis and increased SIG in our
      critically ill patients.

PMID- 14685660
TI  - The European Directive: a further blow to science in intensive care medicine in
      Austria.

PMID- 14685661
TI  - Recombinant activated factor VII in paediatric cardiac surgery.
AB  - OBJECTIVE: To review the use of recombinant activated factor VII in paediatric
      cardiac surgery. DESIGN: Retrospective chart review. SETTING: Paediatric
      intensive care unit in a stand-alone university-affiliated children's hospital.
      PATIENTS AND PARTICIPANTS: Cardiac surgical patients who received recombinant
      activated factor VII (rFVIIa, NovoSeven; NovoNordisk, Copenhagen, Denmark)
      between June 2002 and June 2003 at The Children's Hospital at Westmead. RESULTS:
      Six children undergoing cardiac surgery received rFVIIa. Recombinant activated
      factor VII was administered if bleeding was excessive and persisted despite
      appropriate investigation and attention to haemostasis by surgical and medical
      staff. An intravenous dose of 180 microg/kg was given and repeated 2 h later. All
      of the six patients responded well to rFVIIa with achievement of haemostasis. No
      adverse events were noted. CONCLUSIONS: Recombinant activated factor VII achieved
      haemostasis in six paediatric cardiac surgical patients. Good outcomes and no
      adverse events were noted in these children.

PMID- 14685662
TI  - Volume of activity and occupancy rate in intensive care units. Association with
      mortality.
AB  - OBJECTIVE: Mortality after many procedures is lower in centers where more
      procedures are done. It is controversial whether this is true for intensive care
      units, too. We examined the relationship between the volume of activity of
      intensive care units (ICUs) and mortality by a measure of risk-adjusted volume of
      activity specific for ICUs. DESIGN: Prospective, multicenter, observational
      study. SETTING: Eighty-nine ICUs in 12 European countries. PATIENTS: During a 4
      month study period, 12,615 patients were enrolled. INTERVENTIONS: Demographic and
      clinical statistics, severity at admission and a score of nursing complexity and
      workload were collected. RESULTS: Total volume of activity was defined as the
      number of patients admitted per bed per year, high-risk volume as the number of
      high-risk patients admitted per bed per year (selected combining of length of
      stay and severity of illness). A multi-step risk-adjustment process was planned.
      ICU volume corresponding both to overall [odds ratio (OR) 0.966] and 3,838 high
      risk (OR 0.830) patients was negatively correlated with mortality. Relative
      mortality decreased by 3.4 and 17.0% for every five extra patients treated per
      bed per year in overall volume and high-risk volume, respectively. A direct
      relationship was found between mortality and the ICU occupancy rate (OR 1.324 and
      1.351, respectively). CONCLUSIONS: Intensive care patients, whatever their level
      of risk, are best treated where more high-risk patients are treated. Moreover,
      the higher the ICU occupancy rate, the higher is the mortality.

PMID- 14685664
TI  - Lactic acidosis: an early marker of propofol infusion syndrome?

PMID- 14685666
TI  - [Thoughts on differential diagnosis].
AB  - Referring to H. E. Bock's famous lectures on differential diagnostics, some
      recent developments are discussed. Topical remarks are given concerning modern
      differential diagnostics. In general, they have changed from the diagnostic of
      the phenotype to the detection of the pathogenesis.

PMID- 14685663
TI  - Olanzapine vs haloperidol: treating delirium in a critical care setting.
AB  - OBJECTIVE: To compare the safety and estimate the response profile of olanzapine,
      a second-generation antipsychotic, to haloperidol in the treatment of delirium in
      the critical care setting. DESIGN: Prospective randomized trial. SETTING:
      Tertiary care university affiliated critical care unit. PATIENTS: All admissions
      to a medical and surgical intensive care unit with a diagnosis of delirium.
      INTERVENTIONS: Patients were randomized to receive either enteral olanzapine or
      haloperidol. MEASUREMENTS: Patient's delirium severity and benzodiazepine use
      were monitored over 5 days after the diagnosis of delirium. MAIN RESULTS:
      Delirium Index decreased over time in both groups, as did the administered dose
      of benzodiazepines. Clinical improvement was similar in both treatment arms. No
      side effects were noted in the olanzapine group, whereas the use of haloperidol
      was associated with extrapyramidal side effects. CONCLUSIONS: Olanzapine is a
      safe alternative to haloperidol in delirious critical care patients, and may be
      of particular interest in patients in whom haloperidol is contraindicated.

PMID- 14685667
TI  - [The art of medicine].
AB  - Not too long ago, obtaining a patient's history and performing a physical
      examination was the beginning of every doctor-patient interaction. Today,
      impressing technical methods--extending the human "diagnostic horizon" to an
      unbelievable level of astonishing perception--are easily available in most
      places. So the question comes up whether clinical findings still have relevance
      in common medical practice. This article critically discusses the value of
      apparently "established" clinical signs, but also points out why taking a precise
      patient's history and performing a skilled physical examination is still
      essential-today and tomorrow.

PMID- 14685668
TI  - [Lipoprotein lipase-mediated myopathy: implications for lipid metabolism and
      atherogenesis].
AB  - BACKGROUND: Lipoprotein lipase (LPL) is the central enzyme in plasma triglyceride
      hydrolysis. Various genetically modified mouse lines expressing either native or
      mutated LPL have been established, and the function of LPL in the metabolism and
      during lipoprotein transport has been characterized. Some of these animals showed
      an LPL-mediated myopathy or cardiomyopathy. Comparing the histological changes
      with metabolic data provides new insights in the function of LPL in metabolism
      and for atherogenesis. MATERIAL AND METHODS: Histological and electron microscopy
      specimens of muscle and heart from different LPL transgenic mouse lines have been
      evaluated and compared to metabolic data. RESULTS: Presence of LPL causes a
      myopathy and cardiomyopathy primarily by augmenting nonenzymatic selective
      cholesterol ester uptake. LPL-mediated fatty acid and lipoprotein uptake is not
      sufficient to harm muscle tissue. CONCLUSION: It is suggested, that LPL derived
      from endothelial cells and macrophages--besides other atherogenic mechanisms--can
      mediate cholesterol ester influx into the vessel wall and thereby promote
      proatherogenic modifications. Although due to its hydrolytic function, LPL is
      generally considered an antiatherogenic enzyme, endothelial LPL can locally
      facilitate atherogenesis.

PMID- 14685669
TI  - [Iron as comorbid factor in chronic hepatitis C].
AB  - Hepatitis C virus infection is often associated with an elevation of iron
      parameters. Free liver iron causes liver damage and liver fibrosis preferentially
      through induction of reactive oxygen species. With an allele frequency of 5-10%
      for the C282Y mutation and 6-30% for the H63D mutation, there is a frequent
      coincidence of hemochromatosis (HFE) mutations and chronic hepatitis C. There is
      increasing evidence that HFE homozygosity and even HFE heterozygosity are
      associated with an increased liver iron concentration and liver fibrosis
      progression in chronic hepatitis C. In addition, present data suggest an impact
      of iron on the outcome of interferon therapy. Thus, HFE mutations and liver iron
      stores seem to be important comorbid factors in chronic hepatitis C. Screening
      for iron parameters and HFE mutations should be considered in patients with
      hepatitis C.

PMID- 14685670
TI  - [Drug resistance in antiretroviral therapy of HIV infection].
AB  - Despite impressive success of highly active antiretroviral therapy, a durable
      control of viral replication cannot be achieved in a substantial proportion of
      HIV-infected patients. The most important reason is development of resistance,
      defined as capability of mutant virus to replicate in the presence of a higher
      concentration of substance in comparison to wild-type virus. In the treated HIV
      positive population resistance is prevalent in almost 50%, whereas in treatment
      naive resistance can be found in 10-14%. For diagnosis, genotypic resistance
      tests (sequencing of pol gene) and phenotypic resistance assays (susceptibility
      against antiretrovirals of an isolate in vitro) are available. A special problem
      is the interpretation of complex mutation patterns. Elaborate databases are
      implemented for this task. A number of clinical studies have demonstrated the
      value of resistance testing in the situation of virological failure. Resistance
      guided salvage therapy was significantly more effective in these trials in
      comparison to former standard of care. This led to the recommendation of
      resistance testing in this clinical situation by German and international expert
      panels.

PMID- 14685671
TI  - [Virtual colonography].
AB  - Recent technical developments in computed tomography (CT) and magnetic resonance
      imaging (MRI) have made a virtual presentation of the colon possible. The results
      of clinical investigations comparing virtual colonography and conventional
      colonoscopy up to now are promising. Virtual colonography is a potential tool for
      colorectal carcinoma screening in the future, but it still has an unsatisfactory
      sensitivity for the detection of small and flat lesions and exposes the patient
      to substantial doses of ionizing radiation. Recent investigations using ultra-low
      dose (< 2 mSv) multislice CT colonography show promising results. Magnetic
      resonance (MR) colonography as a radiation-free modality is the technique of the
      future. Although encouraging results using virtual MR colonography for the
      detection of colorectal polyps have been reported, the sensitivity of detecting
      small polyps (</= 10 mm) and flat lesions is poor. Main reason is the limited
      spatial resolution in MRI of the colon. The potential role of virtual
      colonography in the prevention of colorectal cancer is not yet clear. Larger
      studies with asymptomatic persons at average risk are needed, and further
      improvements in the detection of flat and very small (< 5 mm) lesions need to be
      achieved before advocating the use of virtual colonography for routine colorectal
      cancer screening.

PMID- 14685672
TI  - [Clinical genetics of neuroendocrine tumors].
AB  - Neuroendocrine tumors (NETs) are a heterogeneous group of benign and malignant
      neoplasias, detectable in the context of hereditary tumor syndromes in up to 30%
      of cases. The pathogenic understanding of NETs has increased considerably during
      the last decade, mainly due to the identification of underlying genetic defects
      and the availability of genetically modified animal models. These developments
      are reflected in a revised WHO classification of gastrointestinal NETs. In
      contrast to a variety of rare neuroendocrine tumor syndromes, multiple endocrine
      neoplasia syndrome type 1 (MEN1) and type 2 (MEN2) play clinically significant
      roles due to their common incidence. MEN1 and MEN2 are classic autosomal-dominant
      familial tumor diseases with a high penetrance and variable clinical expression,
      caused by germ line mutations of the MEN1 tumor suppressor gene and the RET
      protooncogene, respectively. The clinical management of patients with NETs has
      changed significantly after the introduction of clinical genetic screening. The
      detection of MEN1 mutations allows for risk-adapted treatment and follow-up. RET
      gene analysis can identify individuals with a very high risk to develop familial
      medullary cancer (MEN2), who may be successfully treated by prophylactic
      thyroidectomy. NETs thus represent a paradigmatic example of the successful link
      between basic genetic science and clinical care in molecular medicine.

PMID- 14685673
TI  - [Human lectins and their correspondent glycans in cell biology and clinical
      medicine].
AB  - Lectins are phylogenetically ancient proteins that have specific recognition and
      binding functions for complex carbohydrates of glycoconjugates, i. e., of
      glycoproteins, proteoglycans/glycosaminoglycans and glycolipids. This class of
      proteins mediates important processes of adhesion and communication both inside
      and outside cells. A large variety of lectins are expressed in the human
      organism. This article reviews the current knowledge of human lectins with a
      focus on biochemistry and pathobiochemistry (principles of protein glycosylation
      and defects of glycosylation as a basis of disease) and cell biology (protein
      sorting, exocytosis and endocytosis, apoptosis, cell adhesion, cell
      differentiation, and malignant transformation). The clinical significance of
      lectin-glycoconjugate interactions is described by example of inflammatory
      diseases, defects of immune defense, autoimmunity, infectious diseases, and tumor
      invasion/metastasis. Moreover, therapeutic perspectives of novel drugs that
      interfere with lectin-carbohydrate interactions are discussed.

PMID- 14685674
TI  - [Hyperlipidemia: therapeutic principles in clinical practice].
AB  - Clinical prognosis of coronary heart disease is not only determined by the degree
      of stenosis, but rather by the structure and probability that so-called
      vulnerable plaques rupture. Therefore, the global risk of an individual should be
      considered to recommend specific LDL cholesterol levels in plasma as therapeutic
      goals. For a coronary 10-year risk > 20% the LDL-cholesterol level in plasma
      should be < 100 mg/dl, if the risk is between 10-20% an LDL cholesterol level <
      130 mg/dl, an individual with only one additional risk factor and most probably a
      risk < 10% an LDL cholesterol level < 160 mg/dl is recommended. Recently, the
      committee for practical guidelines of the European Cardiology Society has
      recommended to consider not only the coronary but also the total risk of
      cardiovascular mortality. To reach the recommended therapeutic target levels of
      LDL cholesterol, nonpharmacologic measures should be taken and different classes
      of drugs are available. Several pharmacologic therapeutics are available like
      bileacid sequestrants, nicotinic acid and its derivatives, fibrates, cholesterol
      synthesis inhibitors and the selective inhibitor of intestinal cholesterol
      absorption. The selective inhibition of cholesterol absorption by ezetimibe is a
      novel principle of drug action. Ezetimibe selectively inhibits intestinal
      absorption of free cholesterol and phytosterols. On the basis of this specific
      novel pharmacologic principle of drug action, ezetimibe is useful in the
      combination therapy with statins and can lower LDL cholesterol levels in patients
      with homozygous familial hypercholesterolemia and elevated plasma levels of
      sitosterol and campesterol in patients with sitosterolemia.

PMID- 14685675
TI  - [Conservative treatment of acute pancreatitis].
AB  - The incidence of acute pancreatitis per 100,000 population ranges from 10 to 46.
      The mortality of acute edematous interstitial pancreatitis is < 1%, while
      patients suffering from hemorrhagic necrotizing pancreatitis die from their
      disease in 10-24%. 80% of all cases of acute pancreatitis are etiologically
      correlated to diseases of the biliary tract or an excess alcohol consumption. As
      of today, no specific and causal treatment for acute pancreatitis has been
      established. Early prognostic factors for the evaluation of the clinical course
      of acute eipancreatitis are three or more indicators of organ failure in the
      Ranson or Imrie score, the development of extrapancreatic complications or the
      detection of pancreatic necrosis on contrast-enhanced CT scans. Elevated C
      reactive protein (CRP) levels > 130 mg/l can predict a severe course of acute
      pancreatitis with a high sensitivity. The foundation of medical treatment in
      acute pancreatitis is the substitution of fluids to counteract hypovolemia.
      Furthermore, the relief of sometimes severe visceral pain has the highest
      priority. Infusion of procaine has been found to be ineffective for this purpose.
      The use of antibiotics should be restricted to patients with pancreatic necrosis.
      Enteral nutrition has no adverse effect compared to parenteral nutrition and is
      likely to be beneficial to the course of pancreatitis.

PMID- 14685676
TI  - [New devices in liver replacement therapy].
AB  - Despite the possibilities of liver transplantation, liver failure is still
      associated with a high mortality rate. Liver replacement therapies have been
      developed to bridge the acute decompensation of liver function. A variety of
      artificial and bioartificial devices as well as hepatocyte transplantation are
      already tested in clinical settings. To date, few controlled data are available,
      especially with regard to patient survival. Therefore, liver replacement therapy
      should only be used in clinical studies at specialized centers.

PMID- 14685677
TI  - [Genetic risk factors for hepatic fibrosis in chronic liver diseases].
AB  - Hepatic fibrosis is the result of chronic viral, toxic, autoimmune, or
      cholestatic liver injury. During the complex fibrotic response, hepatic stellate
      cells transdifferentiate into matrix-producing myofibroblasts, and interactions
      between multiple cytokines, receptors and extracellular matrix components
      modulate the fibrotic phenotypes. Of note, course and extent of hepatic fibrosis
      display significant variability among individual patients. These well-known
      differences in progression of hepatic fibrosis have been attributed to age, sex,
      and exogenous factors, e. g., coinfections or alcohol consumption. However, host
      genetic factors are likely to play key roles in the modulation of hepatic
      fibrosis and to contribute to the overall variability in disease progression. In
      recent years, different genetic polymorphisms that may influence the progression
      of hepatic fibrosis have been identified in animal models and human case-control
      studies. These findings indicate that variants of genes encoding immunoregulatory
      proteins as well as pro- and anti-inflammatory cytokines determine liver fibrosis
      in patients with chronic hepatitis C virus infection, alcoholic liver disease,
      and autoimmune liver diseases. However, the results of these studies are mixed
      and restricted to selected known genes. Therefore, definition of consensus
      criteria for association studies and multicenter studies are needed to increase
      statistical power. Genome-wide scans in experimental animal crosses should be
      employed to identify unknown gene loci that confer susceptibility to hepatic
      fibrosis (Hfib loci). In conclusion, genetic association studies have a great
      potential for identification of fibrogenic genes, but large-scale, well-designed
      studies are required to clarify their actual relevance and to provide a solid
      framework for future therapeutic strategies.

PMID- 14685678
TI  - [Matrix metalloproteinases and colorectal cancer].
AB  - Malignant tumors have the ability to invade normal tissue and to spread to
      distant sites giving rise to metastasis, which are major factors in the morbidity
      and mortality of colorectal cancer. Invasion and metastasis involve attachment of
      tumor cells to the basement membrane, degradation of the local connective tissue,
      and penetration and migration through proteolyzed stroma. The key enzymes
      responsible for ECM breakdown are matrix metalloproteinases (MMPs). To date, 26
      MMP genes have been identified in humans, and many are implicated in cancer. ECM
      degradation by MMPs not only enhances tumor invasion, but also affects tumor cell
      behavior and leads to cancer progression. This review highlights recent
      developments with regard to the cellular and molecular mechanisms of MMPs that
      influence colorectal tumor cell growth, invasion, and metastasis.

PMID- 14685679
TI  - [Recent intervention studies with antihypertensive drugs and their influence on
      guidelines].
AB  - Antihypertensive therapy improves the prognosis of essential hypertension.
      Therapy reduces mortality and decreases the incidence of myocardial infarction,
      sudden cardiac death and stroke. Target blood pressure in patients with essential
      hypertension are levels < or = 140/90 mmHg. In patients with essential
      hypertension and concomitant diabetes mellitus type 2, blood pressure should be
      lowered to < or = 130/80 mmHg. Diuretics, beta-blockers, calcium antagonists,
      angiotensin-converting enyzme (ACE) inhibitors, and angiotensin I (AT(1))
      antagonists may nowadays be regarded as drugs of first choice in the treatment of
      essential hypertension. The Joint National Committee in the USA recommends to
      start treatment with a thiazide diuretic. A Guidelines Committee of European
      Society of Hypertension-European Society of Cardiology considers the Endgroups of
      drugs mentioned above to be equally suitable for the initiation and maintenance
      of antihypertensive therapy. Both groups of experts agree that in the majority of
      patients with essential hypertension, a combination of two or more drugs is
      required to reach target blood pressure. Both groups of experts emphasize that
      the main benefits of antihypertensive therapy are due to decreasing blood
      pressure per se.

PMID- 14685680
TI  - [Familial adenomatous polyposis syndrome (FAP): pathogenesis and molecular
      mechanisms].
AB  - The impact that modern molecular biology has had on elucidating the genetic basis
      of neoplasia is best illustrated by the paradigm of sporadic and hereditary colon
      cancer. The clinical and hereditary picture of the familial adenomatous polyposis
      syndrome (FAP) implied the existence of a single gene that regulates the
      formation of adenomatous polyps, the precursor for most colorectal cancers. The
      identification of an interstitial deletion on chromosome 5q in a patient with
      Gardner's variant of FAP combined with classic linkage analysis facilitated the
      positional cloning of the adenomatous polyposis coli (APC) gene in 1991. FAP is
      caused by germline mutations in the APC gene. Somatic mutations in the APC gene
      are an early event in colorectal tumorigenesis, and can be detected in the
      majority of colorectal tumors. APC consists of 8,535 bp spanning 21 exons (16
      translated exons) and encodes a 2,861 amino acid protein that is expressed in
      specific epithelial and mesenchymal cells of several fetal and adult human
      tissues. The APC protein is a large multidomain protein with a molecular mass of
      300 kD. The best-known function of the APC protein is the Wnt-1 signaling
      pathway. Binding Wnt to its receptor, frizzled), leads to the inactivation of the
      glycogen synthase kinase 3 beta in a cytoplasmic complex with APC, beta-catenin,
      axin and components of the ubiquitin ligation machinery. This leads to a decrease
      in beta-catenin phosphorylation and inhibits its proteasomal degradation. As a
      consequence, increased beta-catenin is available to bind transcription factors
      leading to the activation of proliferative genes. In addition, APC has recently
      emerged as a multifunctional protein that can affect a variety of fundamental
      cellular processes, in particular cytoskeletal regulation and chromosomal
      stability. Improved understanding of both the genetics and biology of APC may, in
      time, culminate in preventive or therapeutic strategies specifically targeted at
      reducing the burden of colorectal cancer.

PMID- 14685681
TI  - [Detection of lymph node metastases of malignant melanoma by palpation and
      ultrasound].
AB  - BACKGROUND AND PURPOSE: Early detection of metastases of malignant melanoma has
      therapeutic implications. The aim of this study was to evaluate palpation and
      ultrasound examination in the diagnostics of lymph node metastases in locally
      advanced melanoma. PATIENTS AND METHODS: 83 patients suffering from melanoma
      (Clark level IV or V) were examined for lymph node metastases by palpation and
      sonography. Findings were compared to histopathologic results after lymph node
      extirpation if available or the findings at the next follow-up visit. RESULTS:
      Lymph node metastases were confirmed histopathologically in 14 patients at the
      first study visit, in three others at the control visit. Sensitivity,
      specificity, positive and negative predictive values of palpation for the
      detection of metastases or suspicious nodes with increasing volume at follow-up
      in this population were 65%, 81%, 48%, and 89%, and of ultrasound 100%, 66%, 45%,
      and 100%, respectively. CONCLUSION: Sonography of lymph nodes should be included
      as a standard procedure in the detection of metastases of locally advanced
      malignant melanoma.

PMID- 14685683
TI  - PIAS/SUMO: new partners in transcriptional regulation.
AB  - Protein inhibitor of activated STATs (PIAS) proteins were initially identified as
      negative regulators of cytokine signalling that inhibit the activity of STAT
      transcription factors. Evidence is accumulating that PIAS proteins function as
      transcriptional coregulators in various other important cellular pathways,
      including Wnt signalling, the p53 pathway and steroid hormone signalling. Most
      interestingly, recent work from several laboratories revealed that PIAS proteins
      act as E3-like ligases that stimulate the attachment of the ubiquitin-like SUMO
      modifier to target proteins acting in these pathways. Since in most cases the
      SUMO ligase activity and the transcriptional coregulator activity are
      functionally correlated, the PIAS/SUMO pathway appears to be an important
      mechanism of transcriptional regulation. In this review we will discuss some key
      findings that exemplify the role of PIAS proteins in the regulation of
      transcriptional processes and propose a model how the PIAS/ SUMO system may
      modulate transcriptional activities by mediating the assembly of coactivator or
      corepressor complexes within distinct subnuclear structures.

PMID- 14685684
TI  - Programmed cell clearance.
AB  - Apoptosis, a physiological process of self-annihilation, is essential during
      development and for the maintenance of tissue homeostasis. Considerable efforts
      have been made in recent years to elucidate the molecular mechanisms that govern
      this mode of cellular demise; however, the subsequent recognition and removal of
      apoptotic corpses by neighboring phagocytes has received less attention.
      Nevertheless, macrophage engulfment of apoptotic cells is known to be important
      in the remodeling of tissues, and contributes to the resolution of inflammation
      through the removal of effete cells prior to the release of noxious cellular
      constituents. Moreover, apoptotic cells are a potential source of self-antigens,
      and clearance of cell corpses is thought to preclude the induction of autoimmune
      responses. The view is thus emerging that tissue homeostasis is dependent not
      only on the balance between mitosis and apoptosis, but also on the rate of
      apoptosis versus that of cell clearance. This review aims to discuss the
      mechanisms and consequences of macrophage recognition and disposal of apoptotic
      cells, a process which will be referred to as programmed cell clearance.

PMID- 14685682
TI  - The causes of Charcot-Marie-Tooth disease.
AB  - Charcot-Marie-Tooth (CMT) disease serves as the summary term for the most
      frequent forms of inherited peripheral neuropathies that affect motor and sensory
      nerves. In the last 12 years, 14 genes have been identified that cause different
      CMT subforms. The genes found initially are predominantly responsible for
      demyelinating and dysmyelinating neuropathies. Genes affected in axonal and rare
      forms of CMT have only recently been identified. In this review, we will focus on
      the currently known genes that are associated with CMT syndromes with regards to
      their genetics and function.

PMID- 14685685
TI  - Forming facultative heterochromatin: silencing of an X chromosome in mammalian
      females.
AB  - Compensating for the dosage difference in X-linked genes between male and female
      mammals involves the formation of an extremely stable heterochromatin structure
      on one of the two X chromosomes in females. The inactive X acquires numerous
      features of silent chromatin, including the expression of a noncoding RNA, a
      switch to late replication, histone modifications, recruitment of the histone
      variant macroH2A and DNA hypermethylation. Although the induction of inactivation
      in differentiating mouse embryonic stem cells suggests that the onset of each of
      these features appears to occur in a sequential manner, it is likely that there
      is a much more complex interplay between the different features which leads to
      the extremely stable silencing observed in female somatic cells. Expression of
      the untranslated RNA, XIST, is required in cis for the establishment of the
      heterochromatic state. Recent results have started to elucidate how expression of
      Xist is controlled, including the role of the antisense transcript Tsix.

PMID- 14685686
TI  - The art of war: Innate and adaptive immune responses.
AB  - Research over the last several years has greatly advanced our understanding of
      the mechanisms by which the immune system functions. There exist two main
      branches of immunity, termed innate and adaptive immunity. Innate immunity uses
      the genetic memory of germline-encoded receptors to recognize the molecular
      patterns of common pathogens. Adaptive immunity, akin to somatic memory, is a
      complex system by which the body learns to recognize a pathogen's unique antigens
      and builds an antigen specific response to destroy it. The effective development
      of the overall immune response depends on careful interplay and regulation
      between innate and adaptive immunity. Here we review our current understanding of
      how these integrated systems distinguish targets against which a response is
      appropriate and neutralize potentially pathogenic challenges.

PMID- 14685687
TI  - Pathogenic enterococci: new developments in the 21st century.
AB  - Enterococci, traditionally viewed as Gram-positive commensal bacteria inhabiting
      the alimentary canals of humans and animals, are now acknowledged to be organisms
      capable of causing life-threatening infections in humans, especially in the
      nosocomial environment. The existence of enterococci in such a dual role is
      facilitated, at least in part, by its intrinsic and acquired resistance to
      virtually all antibiotics currently in use. Beginning with the initial
      identification of a 'streptococci of fecal origin' in the late 19th century,
      enterococci have been studied for over a century now. A number of comprehensive
      reviews during this time have addressed various aspects of enterococci, including
      classification, biology, virulence, antibiotic resistance and so on. This review
      specifically addresses the important advances in the field of enterococcal
      research that have occurred since the beginning of the 21st century. Most notable
      among these developments have been the insights into enterococcal genomes and
      pathogenicity.

PMID- 14685688
TI  - Automatic prediction of protein function.
AB  - Most methods annotating protein function utilise sequence homology to proteins of
      experimentally known function. Such a homology-based annotation transfer is
      problematic and limited in scope. Therefore, computational biologists have begun
      to develop ab initio methods that predict aspects of function, including
      subcellular localization, post-translational modifications, functional type and
      protein-protein interactions. For the first two cases, the most accurate
      approaches rely on identifying short signalling motifs, while the most general
      methods utilise tools of artificial intelligence. An outstanding new method
      predicts classes of cellular function directly from sequence. Similarly,
      promising methods have been developed predicting protein-protein interaction
      partners at acceptable levels of accuracy for some pairs in entire proteomes. No
      matter how difficult the task, successes over the last few years have clearly
      paved the way for ab initio prediction of protein function.

PMID- 14685689
TI  - Antimicrobial and cytolytic peptides of venomous arthropods.
AB  - As a response to invading microorganisms, the innate immune system of arthropods
      has evolved a complex arrangement of constitutive and inducible antimicrobial
      peptides that immediately destroy a large variety of pathogens. At the same time,
      venomous arthropods have developed an additional offensive system in their venom
      glands to subdue their prey items. In this complex venom system, several enzymes,
      low-molecular-mass compounds, neurotoxins, antimicrobial and cytolytic peptides
      interact together, resulting in extremely rapid immobilization and/or killing of
      prey or aggressors. This review provides an overview of antimicrobial peptides
      identified in the hemolymph of venomous arthropods, and especially of cytolytic
      peptides in their venom. For these peptides a dual role is proposed: acting as
      antimicrobials as well as increasing the potency of the venom by influencing
      excitable cells.

PMID- 14685690
TI  - Changes in calpastatin localization and expression during calpain activation: a
      new mechanism for the regulation of intracellular Ca(2+)-dependent proteolysis.
AB  - The amount of calpastatin directly available in cytosol is under the control of
      [Ca2+] and [cyclic AMP]. Prolonged calpain activation also promotes degradation
      of calpastatin. The fluctuation of calpastatin concentration in cell soluble
      fraction is accompanied by an initial decrease in calpastatin gene expression,
      followed by a fivefold increase in its expression when the inhibitor protein is
      degraded. This process can be conceptualized as a mechanism to regulate
      calpastatin availability in the cell. This conclusion is supported by the fact
      that calpain, the other component of this proteolytic system, undergoes changes
      in its levels of expression in a much more limited manner. Furthermore, this
      process can be observed both in cells exposed to different natural stimuli, or in
      other cell lines. Modification of calpastatin gene expression might represent a
      new tool for the in vivo control of the regulatory machinery required for the
      modulation of Ca(2+)-dependent proteolysis.

PMID- 14685691
TI  - Neuronal thread protein regulation and interaction with microtubule-associated
      proteins in SH-Sy5y neuronal cells.
AB  - In Alzheimer's disease (AD), neuronal thread protein (NTP) accumulates in
      cortical neurons and colocalizes with phospho- tau-immunoreactive cytoskeletal
      lesions that correlate with dementia. To generate additional information about
      the potential role of NTP in AD, we characterized its expression and regulation
      in human SH-Sy5y neuronal cells. Quantitative real-time reverse transcription
      polymerase chain reactin and Western blot analysis demonstrated prominent
      insulin, moderate insulin-like growth factor, type 1 (IGF-1) and minimal nerve
      growth factor stimulation of NTP expression. In addition, NTP protein was more
      stable and it progressively accumulated in cells that were stimulated with
      insulin for 24 or 48 h. Metabolic labeling and phospho-amino acid analysis
      demonstrated phosphorylation of NTP on Serine residues, 30-60 min after insulin
      or IGF-1 stimulation, when glycogen synthase kinase 3beta (GSK-3beta) activity
      would no longer have been suppressed. Kinase inhibitor and in vitro
      phosphorylation studies demonstrated a role for GSK-3beta in the positive
      regulation of NTP expression and phosphorylation. Coimmunoprecipitation studies
      demonstrated physical interactions between NTP and tau or microtubule-associated
      protein 1b (MAP-1b), and ubiquitin immunoreactivity in NTP immunoprecipitates. In
      summary, these studies showed that (i) NTP expression is regulated at the level
      of transcription by insulin and IGF-1 stimulation; (ii) NTP is phosphorylated by
      GSK-3beta; (iii) NTP can physically interact with tau and MAP-1b and (iv) NTP-MAP
      complexes are ubiquitinated. The results suggest a functional role for NTP in
      relation to the turnover or processing of neuronal cytoskeletal proteins,
      attributes that may be modulated by insulin/IGF-1-mediated signaling.

PMID- 14685692
TI  - Characterization of reverse transcriptase activity of the L1Tc retroelement from
      Trypanosoma cruzi.
AB  - The recombinant protein RTL1Tc, encoded by the non-LTR (long terminal repeat)
      retrotransposon L1Tc from Trypanosoma cruzi, has been shown to have reverse
      transcriptase (RT) activity using poly(rA)/oligo(dT) and poly(rC)/oligo(dG)
      homopolymers as template/primers. The optimal RT activity was detected at a
      concentration of 5 mM Mg2+, pH 8 and between 28 and 37% degrees C. Site-directed
      mutagenesis in the RT catalytic site proved that substitution of aspartic acid
      313 for isoleucine (RT D313IL1Tc) practically abolishes the RT activity of the
      RTL1Tc protein. RT-polymerase chain reaction assays revealed that the RTL1Tc
      protein has the ability to use both homologous and heterologous RNA templates.
      Also, it is shown that the RTL1Tc protein is capable of synthesizing
      complementary DNA molecules by consecutive switching of the oligo molecule, which
      the protein uses as a template. This template switching may be involved in the
      retroelement integration process.

PMID- 14685693
TI  - The expression levels of three raft-associated molecules in cultivated vascular
      cells are dependent on culture conditions.
AB  - Relaying a signal across the plasma membrane requires functional connections
      between the partner molecules. Membrane microdomains or lipid rafts provide an
      environment in which such specific interactions can take place. The integrity of
      these sites is often taken for granted when signalling pathways are investigated
      in cell culture. However, it is well known that smooth muscle and endothelial
      cells undergo cytoskeletal rearrangements during monolayer culturing. Likewise
      affected--and with potentially important consequences for signalling events--is
      the organization of the plasma membrane. The expression levels of three raft
      markers were massively upregulated, and raft-associated 5'-nucleotidase activity
      increased in conventional monolayer cultures as compared with a spheroidal
      coculture model, shown to promote the differentiation of endothelial cells. Our
      data point to a shift of raft components in monolayer cultures and demonstrate
      potential advantages of the spheroid coculture system for investigation of raft
      mediated signalling events in endothelial cells.

PMID- 14685694
TI  - Targeting of the Akt/PKB kinase to the actin skeleton.
AB  - Serine/threonine kinase Akt/PKB intracellular distribution undergoes rapid
      changes in response to agonists such as Platelet-derived growth factor (PDGF) or
      Insulin-like growth factor (IGF). The concept has recently emerged that Akt
      subcellular movements are facilitated by interaction with nonsubstrate ligands.
      Here we show that Akt is bound to the actin skeleton in in situ cytoskeletal
      matrix preparations from PDGF-treated Saos2 cells, suggesting an interaction
      between the two proteins. Indeed, by immunoprecipitation and subcellular
      fractioning, we demonstrate that endogenous Akt and actin physically interact.
      Using recombinant proteins in in vitro binding and overlay assays, we further
      demonstrate that Akt interacts with actin directly. Expression of Akt mutants
      strongly indicates that the N-terminal PH domain of Akt mediates this
      interaction. More important, we show that the partition between actin bound and
      unbound Akt is not constant, but is modulated by growth factor stimulation. In
      fact, PDGF treatment of serum-starved cells triggers an increase in the amount of
      Akt associated with the actin skeleton, concomitant with an increase in Akt
      phosphorylation. Conversely, expression of an Akt mutant in which both Ser473 and
      Thr308 have been mutated to alanine completely abrogates PDGF-induced binding.
      The small GTPases Rac1 and Cdc42 seem to facilitate actin binding, possibly
      increasing Akt phosphorylation.

PMID- 14685695
TI  - Down-regulation of platelet-derived growth factor receptor signaling during
      myogenesis.
AB  - Cell differentiation is often associated with a block in the cell cycle. Growth
      factor signaling has been reported to be impaired in differentiated cells, due to
      the withdrawal of growth factors or to transcriptional down-regulation of their
      receptors. Our proposal is that the down regulation of growth factor signaling
      may be achieved through an alternative pathway: the decrease of growth factor
      receptor activation and the ensuing inhibition of intracellular pathways leading
      the cell to division. Here we report that platelet-derived growth factor receptor
      (PDGFr) signaling is down-regulated during muscle differentiation, although its
      expression level remains unchanged. PDGFr signaling inhibition is achieved
      through a decrease in the receptor tyrosine phosphorylation level, in particular
      of Tyr716, Tyr751, Tyr857 and Tyr1021, leading to down-regulation of
      intracellular signaling pathways. Furthermore, during myogenesis, the expression
      level of several phosphotyrosine phosphatases (PTPs) increases and most of them
      shift toward the reduced/activated state. We propose a causal link between the
      down-regulation of PDGFr tyrosine phosphorylation and the increases in PTP
      specific activity during myogenesis.

PMID- 14685696
TI  - c-Fos but not v-Fos protein induces programmed cell death of v-myb-transformed
      monoblasts.
AB  - c-Fos and v-Fos belong to a group of proteins forming the transcription factor AP
      1 that is important for regulation of proliferation, differentiation and
      programmed cell death in multiple cell types. In this study, we examined the role
      of c-Fos and v-Fos proteins in v-myb-transformed BM2 monoblasts. We show that
      while the v-Fos protein prolongs the G0G1 phase of the BM2 cell cycle, c-Fos
      leaves the cell cycle unaffected and, rather, induces programmed cell death. The
      apoptosis-promoting activity of the c-Fos protein is markedly enhanced in cells
      cultivated under serum-free conditions. c-Fos-induced apoptosis of BM2 cells
      occurred in the presence of Bcl-2 and was not dependent on the transcription
      activation function of the c-Fos protein. No differentiation-promoting activity
      of the Fos proteins was observed. The effects of Fos proteins on BM2 cells differ
      from those induced by Jun proteins, suggesting differential roles of individual
      components of the AP-1 transcription factor in regulation of essential cellular
      processes.

PMID- 14685697
TI  - Pancreastatin, a chromogranin A-derived peptide, inhibits leptin and enhances UCP
      2 expression in isolated rat adipocytes.
AB  - Leptin, the ob gene product, is an adipocyte-secreted hormone that centrally
      regulates weight by decreasing caloric intake and increasing energy expenditure.
      Expression of leptin is regulated by dietary status, insulin, glucocorticoids and
      catecholamines. Pancreastatin (PST), a chromogranin A-derived peptide, correlates
      with catecholamine levels, and may play a role in the physiology of stress,
      modulating endocrine secretion and metabolism. Thus, PST has been found to exert
      a lipolytic and anti-insulin effect in white adipocytes. The aim of the present
      work was to investigate a possible role of PST modulating the expression of key
      genes involved in lipid storage and metabolism: leptin, PPAR-gamma2, UCP-1 and
      UCP-2. We incubated isolated rat epididymal adipocytes with 100 nM PST for 16 and
      24 h. Leptin, UCP-2 and UCP-1 mRNA levels were assessed by RT-PCR, followed by
      Southern blot. Leptin secretion was also measured by ELISA. PST inhibited leptin
      expression and secretion at 16-h incubation, but this effect was no longer
      observed after 24 h. On the other hand, PST stimulated the expression of UCP-2
      after 16 h. However, the effect was still significant after 24 h. The inhibitory
      effect of PST on leptin expression and secretion and the stimulation of UCP-2
      expression were prevented by blocking PKC. UCP-1 and PPR-gamma2 expression did
      not change after PST stimulation. Leptin differentially regulates the expression
      of key genes in the rat adipocyte, upregulating the expression of UCP-2 and
      inhibiting the expression and secretion of leptin by a mechanism that involves
      PKC activity. These effects may contribute to the metabolic action of
      catecholamines in physiological and pathophysiological conditions with increased
      sympathetic activity.

PMID- 14685698
TI  - Sphingosine 1-phosphate signal survival and mitogenesis are mediated by lipid
      stereospecific binding of triacylglycerol-rich lipoproteins.
AB  - Proof for the role of triacylglycerol-rich lipoproteins (TRLs) in the development
      of cardiovascular events is accumulating. We recently reported that postprandial
      TRLs bind to and internalize into human aortic vascular smooth muscle cells (HA
      VSMCs) by a lipid-dependent mechanism. We now show that postprandial TRLs
      triggered hydrolysis of sphingomyelin and stimulation of the sphingosine kinase
      producing sphingosine 1-phosphate (S1P). In addition, postprandial TRLs exhibited
      survival and mitogenic effects. Interestingly, the signals were modulated by the
      nature of the fatty acids located at the sn-2 position in the triacylglycerol
      molecules of TRL. This lipid-stereospecific regulation of S1P cellular levels in
      HA-VSMCs provides a novel insight into the intrinsic role of dietary fatty acids
      and the mechanism mediated by triacylglycerol-containing postprandial
      lipoproteins in the pathogenesis of atherosclerosis.

PMID- 14685699
TI  - Signal transduction through nuclear factor kappa B in ischemia-reperfusion and
      heart failure.
AB  - Ischemic heart disease is the major cause of morbity and mortality in the Western
      world, with chronic heart failure as one complication. Ischemia-reperfusion
      injury may induce cardiomyocyte cell death by necrosis or apoptosis. The heart
      can be adapted to tolerate an ischemic event by preceeding brief episodes of
      ischemia and reperfusion, called preconditioning. Innate immunity has the latest
      years surfaced as important for the development of cardiovascular pathology as
      well as for myocardial protection. Nuclear factor kappa B (NFkappaB) is a redox
      sensitive transcription factor which contributes to the regulation of innate and
      adaptive immunity. NFkappaB regulates a battery of inflammatory genes, and has
      been indicated to play a role in the development of numerous pathological states.
      Activation of NFkappaB induces gene programs leading to transcription of factors
      which promote inflammation, among them leukocyte adhesion molecules, cytokines
      such as tumor necrosis factor alpha, and chemokines, but may in some situations
      also promote tissue remodelling, the resolution of inflammation, and
      transcription of some few substances with possible antiinflammatory effects. The
      present paper reviews the basic regulation of NFkappaB, and the possible role of
      NFkappaB activation in ischemia-reperfusion injury, in adaptation to ischemia
      reperfusion injury, and in chronic heart failure.

PMID- 14685700
TI  - TNFalpha in ischemia/reperfusion injury and heart failure.
AB  - During myocardial ischemia, both the myocardial and serum TNFalpha concentrations
      are rapidly increased within the area at risk. With prolongation of ischemia and
      development of cardiomyocyte necrosis, the TNFalpha concentration increases also
      in the surrounding viable portions of the myocardium. Indeed, in the scenario of
      myocardial ischemia/reperfusion, treatment with TNFalpha antibodies reduced the
      extent of myocardial infarction in rabbits and attenuated the contractile
      dysfunction following microembolization in dogs. In the latter studies, the serum
      TNFalpha concentration remained unaltered thereby supporting the notion of a
      direct action of TNFalpha at the level of cardiomyocytes during
      ischemia/reperfusion. In heart failure, the serum TNFalpha concentration is also
      increased, and in patients with advanced heart failure the serum TNFalpha
      concentration is an independent predictor of mortality. The origin of the
      increased serum TNFalpha concentration is not clearly identified yet, but
      TNFalpha derived from the heart and peripheral organs contributes to the
      increased serum TNFalpha concentration. Treatment with TNFalpha antibodies in the
      clinical scenario, however, did not improve the prognosis of heart failure
      patients.

PMID- 14685701
TI  - TNFalpha in patients with congestive heart failure.
AB  - It is now generally accepted that chronically extensive stimulation of the
      cytokine system-and of TNFalpha in particular-is detrimental to the heart and to
      peripheral tissue and that such stimulation may contribute to the pathogenesis of
      congestive heart failure of various causes. During the past decade, basic and
      clinical research has provided growing evidence for the role of systemic and
      local inflammatory responses that, however, have so far failed to translate into
      new treatments for patients. The present paper represents an attempt to
      critically review the general concepts that lie behind the dichotomy existing
      between an impressive bulk of biologic research showing the role of TNFalpha as a
      pathogen in congestive heart failure and the difficulties in translating this
      evidence into patients' treatment.

PMID- 14685702
TI  - Tumour necrosis factor-alpha and the failing heart--pathophysiology and
      therapeutic implications.
AB  - Immune activation plays a significant role in the development and progression of
      chronic heart failure (CHF). Indeed, pro-inflammatory cytokines, especially
      tumour necrosis factor-alpha (TNFalpha) are activated in this condition and exert
      direct detrimental actions on the myocardium. Physiological dampeners of TNFalpha
      production, such as interleukin-10, catecholamines, cortisol, and others fail in
      the course of the disease. However, the outcomes of two large-scale clinical
      trials with etanercept and infliximab, which directly antagonise TNFalpha have
      been rather disappointing. Nevertheless, TNFalpha antagonism remains a major
      target of CHF therapy, although counterbalancing this cytokine alone may not be
      sufficient.

PMID- 14685703
TI  - Exogenous activation of delta- and kappa-opioid receptors affords
      cardioprotection in isolated murine heart.
AB  - Controversy exists regarding the relative roles of delta- and kappa-opioid
      receptor activation as a potential cardioprotective mechanism. Furthermore, the
      function of opioid receptor activation in cardioprotection has not been examined
      in the murine heart. To this end, we employed various concentrations of selective
      delta - and kappa-opioid receptor agonists in an isolated murine heart model
      undergoing 20 min global ischemia followed by 45 min reperfusion. Left
      ventricular developed pressure (LVDP) returned to 50.7 +/- 2.1% of baseline
      values in untreated hearts. Infusion of the non-selective opioid agonist,
      morphine (10 micro M), lead to a marked improvement in post-ischemic contractile
      recovery where LVDP returned to 65.5 +/- 2.4% of baseline function. The delta
      opioid selective agonist BW373U86 hydrochloride elicited maximal protection at a
      concentration of 1 micro M which afforded 63.9 +/- 3.4% recovery of LVDP. This
      effect was blocked by the delta-opioid selective antagonist, BNTX. Furthermore,
      administration of the kappa-opioid selective agonist U50,488 (1 micro M) produced
      a marked improvement in contractile recovery leading to a 72.5 +/- 5.3% recovery
      of LVDP. This degree of protection was also abolished by the kappa-opioid
      receptor antagonist, nor-BNI. No differences were noted in LDH efflux from post
      ischemic hearts. These data suggest that exogenous activation of delta- and kappa
      opioid receptors afford protection against myocardial stunning in the isolated
      murine heart, an effect attenuated by selective receptor antagonists.

PMID- 14685704
TI  - Delayed cardioprotection is mediated via a non-peptide delta opioid agonist, SNC
      121, independent of opioid receptor stimulation.
AB  - Acute cardioprotection is mediated primarily through delta opioid receptor
      stimulation independent of micro or kappa opioid receptor stimulation. Delayed
      cardioprotection is mediated by delta opioid receptor agonists but ambiguity
      remains about direct receptor involvement. Therefore, we investigated the
      potential of SNC-121, a non-peptide delta opioid agonist, to produce delayed
      cardioprotection and characterized the role of opioid receptors in this delayed
      response. All rats underwent 30 minutes of ischemia followed by 2 hours of
      reperfusion. SNC-121 induced a significant delayed cardioprotective effect. To
      determine the nature of this SNC-121-induced delayed cardioprotection, rats were
      treated with specific opioids receptor antagonists and underwent pertussis toxin
      (PT) treatment prior to opioid agonist stimulation. Control rats were injected
      with saline and allowed to recover for 24 hours. Pretreatment and early treatment
      with opioid receptor antagonists failed to inhibit the delayed protective effects
      of SNC-121, as did pretreatment with PT. Treatment with a free radical scavenger,
      2-mercaptopropionyl glycine, at the time of opioid stimulation attenuated the
      delayed cardioprotective effects of SNC-121. These data suggest that delayed
      cardioprotection is stimulated via non-peptide delta opioid agonists by a
      mechanism unrelated to opioid receptor activation. The mechanism appears to be a
      non-opioid receptor mediated production of reactive oxygen species that triggers
      the signaling cascade leading to delayed cardioprotection.

PMID- 14685705
TI  - Gender and aging do not impair opioid-induced late preconditioning in rats.
AB  - Opioids have been shown to confer late preconditioning against
      ischemia/reperfusion injury in several species. However, it is unknown whether
      gender or aging affects opioid-induced cardioprotection. Isolated perfused hearts
      from Fischer 344 rats were subjected to 20 min of global ischemia followed by 20
      min of reperfusion. BW373U86, a delta-opioid receptor agonist, was administered
      s.c. at varying doses (0.1, 0.33, 1.0 mg/kg) 24 h before (BW0.1, BW0.33 and
      BW1.0, respectively). In 12-week-old male (YM) rats, the recovery of LV developed
      pressure (LVDP) after ischemia/reperfusion improved significantly in BW0.33 and
      BW1.0, compared with the control (C). In 78-week-old male (OM) rats, the recovery
      of LV function after ischemia/reperfusion improved and the total release of CK
      and LDH during reperfusion was attenuated in BW1.0. In 12-week-old female (YF)
      rats, the recovery of LV function improved only in BW0.33 but not in BW0.1 and
      BW1.0. The cardioprotective effect afforded by BW373U86 was completely abolished
      by NS-398, a COX-2 selective inhibitor, in YM, YF, and OM, although NS-398 in
      itself did not affect myocardial ischemia/reperfusion injury. The levels of 6
      keto-PGF(1alpha) (a stable metabolite of PGI(2)) in coronary effluent during
      reperfusion were higher in the BW373U86-pretreated group that showed
      cardioprotection than in C and this increase in PGI(2) production was also
      inhibited by NS-398 in YM, YF, and OM. In conclusion, BW373U86-induced late
      preconditioning can be observed in aged and female hearts. A COX-2-dependent
      increase in PGI(2) production is essential for BW373U86-induced late PC in both
      sexes and in both young and old rats.

PMID- 14685706
TI  - Influence of the point of origin on heart rate turbulence after stimulated
      ventricular and atrial premature beats.
AB  - BACKGROUND: Heart rate turbulence (HRT) is a new and auspicious parameter for
      risk stratification in patients suffering from structural heart disease. The HRT
      parameters onset (TO) and slope (TS) are derived from Holter ECGs. Only a few
      studies have evaluated physiologic properties like age or prematurity of the
      ventricular beat on HRT. Until now, to our knowledge, little is known about the
      influence of the point of origin of the premature beat on HRT. Therefore, we
      conducted a study consisting of 25 patients (pts) with premature beats generating
      from 2 different sites in the atrium and ventricle. METHODS: During an
      electrophysiologic study, premature extra beats were induced. The high right
      atrium (HRA) and the lateral part of the coronary sinus (CS) represented the
      atrial pacing sites, while the right ventricular apex (RVAP) and right
      ventricular out flow tract (RVOT) represented the ventricular pacing sites.
      Prematurity started at 450 ms and was decreased to the refractoriness of each
      site. TO and TS were computed and correlated to the site of origin and the
      coupling interval (CI). RESULTS: Atrial TO was positive in 9 pts (HRA) and 7 (CS)
      as well as ventricular TO in 2 pts, respectively. TO induced in CS correlated
      with the CI (r = -0.50, p < 0.05). TS was negative, independent of the site of
      origin. Atrial TS showed no correlation with the CI. TO generated from both
      ventricular sites was positive in 2 pts. TO from RVAP correlated with the CI (r =
      -0.81, p < 0.005), but not with RVOT. TS from both ventricular sites exhibited no
      correlation with the pacing site, but correlated with themselves (r = -0.69, p <
      0.03). CONCLUSION: The site of origin of the premature beat exhibits no influence
      on heart rate turbulence slope. The prematurity of the extra beat correlates with
      turbulence onset, but not with slope. Finally, the site of origin revealed no
      influence on HRT slope. Therefore, the calculation of heart rate turbulence
      derived from extra beats extracted from Holter ECG is reliable.

PMID- 14685707
TI  - Statin therapy in patients with coronary artery disease improves the impaired
      endothelial progenitor cell differentiation into cardiomyogenic cells.
AB  - Human endothelial progenitor cells (EPCs) can differentiate into cardiomyogenic
      cells in vitro. We tested the effects of statin therapy on the differentiation
      rate of EPCs from patients with coronary artery disease (CAD), who may benefit
      from autologous cell therapy.EPCs from 3 age-matched groups were tested: No CAD
      (n = 13), CAD patients with (n = 10) or without (n = 16) statin therapy. From 4
      CAD patients, EPCs were tested before and after 4 weeks of therapy with 20 mg
      atorvastatin. After 6 days of co-culture with rat neonatal cardiomyocytes, EPC
      differentiation was quantified by immunostaining for alpha-sarcomeric actinin
      flow cytometry analysis. After 6 days of co-culture, the percentage of 
      sarcomeric actinin-positive EPCs was significantly (p = 0.014) higher in EPCs
      from adults without CAD (8.07% +/- 1.48% of EPCs) compared to EPCs from CAD
      patients without statin (3.56% +/- 0.72%). Importantly, patients with statin
      therapy revealed significantly higher numbers of alpha-sarcomeric actinin
      positive EPCs (6.36% +/- 0.69%, p = 0.01) compared to CAD patients without
      statin. In addition, statin therapy resulted in a significant (p = 0.017)
      increase of EPC differentiation in all 4 CAD patients investigated before and 4
      weeks after statin therapy. The survival of EPCs did not differ between the
      different groups suggesting that the regulation of EPC differentiation is not
      secondary to altered EPC survival. In vitro, EPC treatment with 0.1 micro M
      atorvastatin did not affect EPC differentiation (116.15% +/- 49.11% of
      control).EPCs from patients with CAD display impaired differentiation into
      cardiomyogenic cells. This defect can be improved by in vivo, statin therapy.

PMID- 14685709
TI  - [Osteoporosis].

PMID- 14685710
TI  - Hormone replacement therapy: what is the evidence today?
AB  - Based on the most recent studies, it clearly appears that long-term hormone
      replacement therapy (HRT) prevents fractures but does not improve established
      coronary artery disease. In addition, HRT leads to a small increase in breast
      cancer incidence and to a decrease in colorectal cancer incidence. HRT increases
      the incidence of venous thrombosis, pulmonary embolisms and strokes. As a
      consequence, HRT can no longer be recommended for primary or secondary prevention
      of cardiovascular diseases. In addition, it was also demonstrated that HRT was
      not able to improve cognitive functions and prevent dementia. Therefore regarding
      daily clinical practice, HRT certainly remains useful to control the symptoms of
      oestrogen deficiency in recently menopausal patients, but it should definitively
      no longer be recommended for long-term treatment.

PMID- 14685711
TI  - [Therapy of osteoporosis: bisphosphonates, SERM's, teriparatide and strontium].
AB  - The therapy of osteoporosis is mostly based upon the use of drugs which inhibit
      bone resorption. Among these, the bisphosphonate family is the best known and
      mostly used by clinicians. Both second and third generation bisphosphonates, like
      alendronate and risedronate, are now available as weekly tablets which have
      facilitated the patient compliance to treatment together with a decreased
      occurrence of gastrointestinal side effects. These compounds are used efficiently
      to treat postmenopausal osteoporosis and osteoporosis of men as well. Their use
      did provide good evidence of increased bone mineral density (BMD) and a reduction
      in fracture rates. The use of intravenous bisphosphonates such as Zoledronate,
      Ibandronate and Pamidronate remains in most of the cases limited to special
      indications such as intolerance to the oral formulations and treatment of
      patients with bone metastases. The selective estrogen modulators (SERM's) family
      is limited to a single product on the market as of now, Raloxifene, which does
      inhibit bone resorption and is well documented by postmenopausal women to
      increase BMD and reduce vertebral fractures. In addition, a large range of
      positive nonosseous effects have been documented such as the reduction of the
      incidence of breast cancer. Other substances do have a strong anabolic effect
      such as Teriparatide, a recombinant human formulation of PTH 1-34. This compound
      has demonstrated good efficacy in postmenopausal women, increasing vertebral and
      hip BMD and reducing the incidence of fractures at both sites. The exact role of
      Teriparatide in the clinical setting is still open but its overall impact in the
      therapy of osteoporosis could be major due to its major efficiency over shorter
      periods of time. Strontium ranelate, a new divalent Strontium salt taken orally,
      acts both as an anti-catabolic and anabolic agent. The first results provided
      with strontium ranelate are very promising due to its major effect on the
      increase in BMD both at the vertebral and hip sites and its ability to reduce the
      incidence of fractures at both locations. Additional data are awaited to confirm
      these initial positive results.

PMID- 14685712
TI  - [Effect of vitamin D on muscle strength and relevance in regard to osteoporosis
      prevention].
AB  - A successful prevention strategy for fractures in the elderly should not be
      limited to an improvement in bone mineral density. Equally important is the
      prevention of falls. Thus, 90% of fractures in the elderly are associated with a
      fall and 30% of all ambulatory, and 50% of institutionalized elderly age 65 years
      and older fall at least once a year. Fall incidence increases 10% per decade
      thereafter. According to recent studies, vitamin D and calcium supplementation
      may be a promising treatment strategy targeting both bone mineral density, as
      well as muscle strength and the risk of falling. The protective effect of vitamin
      D on fractures has been attributed to the established moderate benefit of vitamin
      D on bone mineral density. However, an alternative explanation might be that
      vitamin D affects factors directly related to muscle strength, thus, reducing
      fracture risk through improved function and fall prevention, in addition to its
      benefits on calcium homeostasis.

PMID- 14685713
TI  - [Physiotherapy interventions in osteoporosis].
AB  - Osteoporosis is an increasing public health problem which ultimately causes
      fractures and a significant reduction in patient's health-related quality of
      life. In this context, physiotherapists are involved in a wide range of therapies
      related both to prevention and treatment of osteoporosis. The reduction of the
      risk of falling by elderly patients with osteoporosis is a very important goal
      for physiotherapists because it is known to significantly decrease fracture
      incidence. Indeed, exercise programs including elements of muscle strengthening
      and better body balance control have a positive effect on the risk of falling,
      hence reducing the incidence of fractures and increasing the health-related
      quality of life of osteoporotic patients. As a further consequence, the decreased
      fracture incidence has a key roll in reducing health care costs. Once a patient
      presents with an osteoporotic fracture, he may be assisted with various forms of
      passive, active-assisted and active therapies. This treatment will help reduce
      pain, increase patient's mobility and prevent the occurrence of additional
      fractures. In addition, a good and well-balanced education process regarding
      secondary osteoporosis prevention may also help to modify the behavior of
      patients and help to improve skeletal health in the longer term. The
      physiotherapist has definitively a major role to play in the interdisciplinary
      team aimed at preventing osteoporotic fractures in both primary and secondary
      prevention levels.

PMID- 14685714
TI  - [Chronic recurrent multifocal osteomyelitis in association with chronic
      inflammatory bowel disease: entheropathic CRMO].
AB  - The enterogenic reactive arthritides and entheropathic spondyloarthropathies are
      well-known entities. The so-called gut iteropathy concept offers an interesting
      working hypothesis to link the gut inflammation and the lymphocytic infiltration
      of the synovium. However, the association of rheumatic diseases belonging to the
      entity of the SAPHO syndrome with inflammatory bowel diseases (IBD) has only been
      rarely described in the literature. Among 138 cases of our (heterogenic) SAPHO
      cohort, we detected 5 patients (1 male, 4 females) with a proven association of
      SAPHO syndrome with IBD (in 4 cases Crohn's disease, in 1 case ulcerative
      colitis). Two patients belonged to the juvenileadolescent form and 3 to the adult
      form of SAPHO syndrome. In all cases the underlying osteoarticluar disease was
      classified as chronic recurrent multifocal osteomyelitis (CRMO), 2 of them
      presenting as inflammatory anterior chest wall syndrome. There was a strong
      association with psoriatic pustular dermatitis. Thus, we present 5 cases of
      "enteropathic CRMO" demonstrating several analogies to the enteropathic
      spondyloarthropathies. Both disease entities have in common i) metachronic
      development with osteoarticluar manifestations often preceding the
      gastrointestinal disease; ii) Crohn's like lesions that may develop from the
      stomach to the colon; iii) concomittent or intermittent skin pustulosis which
      mostly resolves; iiii) the gastrointestinal disease that often dominates the
      whole syndrome namely in the longterm follow-up. We suggest to transfer the
      hypothesis of the gut-synovium axis of enteropathic spondyloarthropathies to the
      entity of CRMO. This concept offers an opportunity to link the target organs gut
      mucosa, bone marrow and the skin via homing of antigen specific lymphocytes. This
      concept may help to better understand the pathogenesis of the "Skibo" (i. e.,
      skin-bone) disease CRMO.

PMID- 14685715
TI  - [Polymorphonuclear granulocytes in rheumatic tissue destruction VIII.
      Considerations on the inflammatory cartilage destruction in chronic arthritides
      in comparison with liver injuries by PMN's].
AB  - Inflammatory cartilage destruction in chronic arthritides is usually regarded as
      the process owing to chondrocytic chondrolysis or ingrowth of pannus tissue.
      Besides these two mechanisms a third one-cartilage degradation directly mediated
      by polymorphonuclear granulocytes (PMN's) of the synovial fluid-seems to be
      underestimated. There is growing evidence that PMN's are involved in several non
      bacterial organ destructions (e.g., alcoholic hepatitis); thus, two case reports
      are presented demonstrating cartilage destruction by PMN's via the synovial
      fluid. It is shown by light and electron microscopy that in florid rheumatoid
      arthritis, PMN's from the inflamed synovial fluid can gain access to the
      cartilaginous surface. The adherence of PMN's to the superficial matrix,
      eventually mediated by immunocomplexes, may activate these cells with the
      subsequent secretion of destructive enzymes as well as reactive oxygen species.
      Cartilage degradation may be the consequence. From the morphological findings it
      is deduced that this mechanism may have important implications for inflammatory
      cartilage loss.

PMID- 14685717
TI  - [Reliability, validity and responsiveness of the German short musculoskeletal
      function assessment questionnaire (SMFA-D) in patients with osteoarthritis of the
      hip undergoing total hip arthroplasty].
AB  - BACKGROUND: The aim of the present study was to check for reliability, validity
      and responsiveness of the Musculoskeletal Function Assessment questionnaire (SMFA
      D) in patients with coxarthrosis undergoing total hip replacement. PATIENTS AND
      METHOD: In a prospective clinical trial the SMFA-D, the SF-36, the Harris Hip
      score, test of walking speed and the functional impairment according to the
      physician assessment were recorded. RESULTS: The reliability of the instrument
      could be demonstrated by a correlation coefficient of r = 0.78 for the function
      index and r = 0.84 for the bother index. Patients could be distinguished by the
      physician's assessment to show discriminative validity. Both indices correlated
      significantly with the Harris Hip score, scales of the SF-36 and the walking
      speed supporting the construct validity. The responsiveness could be shown with
      large effect sizes (1.04 for the function index and 1.02 for the bother index) at
      the three-month follow-up. CONCLUSIONS: The SMFA-D was found to be a reliable,
      valid and responsive instrument in patients with coxarthrosis undergoing hip
      replacement and the use of this instrument can be recommended.

PMID- 14685718
TI  - [Imaging techniques in rheumatology: scoring methods in rheumatoid arthritis].
AB  - This is a critical overview of existing scoring methods including their basis,
      their measurement systems, their advantages and disadvantages. Conventional
      radiography is still-since available everywhere, interpretable and cost effective
      the best imaging method to evaluate the course of RA. Scoring methods are
      designed to semiquantitatively measure radiographically visible changes,
      especially erosive destruction and-in part-cartilage loss. These methods are well
      validated, reproducible, and yield similar results in clinical trials. Most
      methods overestimate early changes and have a clear ceiling effect. Within the
      time frame of clinical trials radiographic evaluation is not very sensitive to
      change since the progression of destruction in RA is relatively slow. Moreover,
      small erosions cannot be detected if they are not at the margin of the bone or if
      they are superimposed by other bones. Within the Larsen method the definition of
      grade 1 by soft tissue swelling is disadvantageous: soft tissue swelling is
      difficult to identify on X-rays, it is a measure of disease activity and not of
      destruction and is quickly reversible. Joint space narrowing, measured with
      Sharp's method and its modifications, may be caused by misprojection due to soft
      tissue swelling with flexion or subluxation of the joint rather than cartilage
      loss. Since the measurement error of a scoring method is very much dependent on
      the severity of the disease of the patient population and on the quality of the
      radiographs, the measurement error and thereby the minimal detectable change
      (MDC) should be stated for every single clinical trial. Conventional radiographs
      and scoring methods are still indispensable to measure the influence of treatment
      on radiographic progression in RA. A future task will be to include in scoring
      methods the rating of reparative changes which cannot be scored so far.

PMID- 14685719
TI  - [Phlegmon of the forearm due to therapy with Anakinra (interleukin-1 receptor
      antagonist)].
AB  - INTRODUCTION: Biological modifiers (BM) are very effective in a high percentage
      of patients with rheumatoid arthritis being resistant to disease modifying
      antirheumatic drugs (DMARD). In the beginning, the therapy with the BMs was
      thought to be of low risk. However, due to the increase of application, a few
      lethal septical complications have been reported. CASE REPORT: A 38 year old male
      with rheumatoid arthritis and insulin deficiency diabetes mellitus achieved
      remission under the therapy with Anakinra within three days. Due to a spontaneous
      disrupture of the finger extensor tendons operative revision was performed. A
      phlegmon from the dorsum of the hand to the cubita was found five months after
      resection of a septical cubital bursa. CONCLUSION: The very effective suppression
      of the immune system by the BMs should not lead to noncritical therapy in
      patients with history of infections of bone, joints and soft tissue, because
      inactive organism may start growing and lead to undetected lethal sepsis.

PMID- 14685720
TI  - An overwhelming pulmonary fungus ball in a systemic lupus erythematosus patient.
AB  - Impaired host immunity has been regarded as a predisposing factor in post-primary
      tuberculosis in adults. Patients with systemic lupus erythematosus (SLE) are
      usually exposed to high doses of corticosteroids and eventually develop defective
      cellular immunity that increases the risk for active tuberculosis. SLE-associated
      pulmonary tuberculosis tends to have a higher incidence of miliary, far-advanced
      pulmonary disease and therefore establishing the diagnosis can easily be delayed
      due to generalized, non-specific clinical symptoms such as fever, malaise and
      weight loss which are also commonly observed in lupus patients. However, cavitary
      tuberculosis is very rare in patients with SLE. To the best of our knowledge,
      fungus ball formation in the tuberculosis cavity in a patient with SLE, has not
      been previously reported. Thus, we present a case of SLE who was found to have a
      fungus ball within a preexisting tuberculosis cavity. The diagnosis was resolved
      by computerized tomography of the chest and was confirmed with histopathological
      examination.

PMID- 14685721
TI  - [Hans Reiger and oculo-urethro-synovial syndrome. 1. History of the disease].

PMID- 14685730
TI  - [Quality of life of the aged. Findings and intervention approaches].

PMID- 14685731
TI  - [Learning in old age: The importance of self-initiated structuring].
AB  - The purpose of the present study was to assess the role of memory, inhibition
      efficiency and self-initiated structuring of learning material in predicting age
      related effects in learning performance. 47 young ( M = 23.3; SD = 3.8) and 52
      old adults ( M = 64.5; SD = 5.2) took part in the current study. Tests assessing
      memory span, inhibition efficiency and a recall test requiring the participants
      to structure their learning material were administered. The results reveal that
      most of the age-related variance in learning performance can be explained by
      inhibition efficiency, memory span and-particularly-by the quality of structuring
      learning material. Furthermore, the results indicate that in order to recall the
      content of categories it is important to remember the categories formed during
      the learning period. The study emphasizes the importance of teaching strategies
      for organizing learning material in the context of cognitive trainings for the
      elderly.

PMID- 14685732
TI  - [Similarities and differences between self-rated and proxy-rated health in
      extreme old age].
AB  - Especially in old age, the global well-being of persons is strongly influenced by
      their health situation. Due to functional limitations, research on the
      development of persons in extreme old age often uses proxy ratings of health
      instead of self-ratings common in younger age groups. However, it is not known
      whether self- and proxy-ratings provide comparable information about the health
      status of extremely old persons. The current study with 53 centenarians and 53
      proxies examines similarities and differences between self and proxy-ratings of
      health. The results indicate a high degree of similarity in some health ratings,
      an overestimation of ADL capacities by the centenarians, and that self-ratings to
      a large degree reflect the current mood levels of individuals. Findings are
      discussed with respect to the differences in the kind of information used for
      general health ratings.

PMID- 14685733
TI  - [Functional competence and nursing care in centenarians. The importance of the
      cognitive status].
AB  - The maintenance of autonomy and independence in the oldest old population is at
      high risk due to the inevitable aging process, which primarily affects functional
      and cognitive capacities. In this study, we investigate centenarians to assess
      the extent in which they have lost their ability to live independently. This is
      done with a classification system for dependency that considers both functional
      and cognitive limitations and determines the level of functional competence in
      this population. Based on this system, we evaluate the necessity for nursing care
      and investigate to which extent their actual needs are covered by the German Long
      term Care Insurance. An important and relevant question is whether this system
      even addresses the evaluation of cognitive impairment. For this reason, 85
      centenarians and their proxies were assessed with standardized instruments and
      the results show a severe loss of independence. The necessity for at least daily
      contact with nursing care was identified in 91 percent of the centenarians due to
      their dramatically limited capacities. Forty-four percent of the centenarians
      need more support than they actually receive from the German Long-term Care
      Insurance. Therefore, considering cognitive impairment is a crucial component in
      the evaluation, which would lead to more support by the official system in 20
      percent of the centenarians. The considerable differences between the granted and
      the necessary nursing care demonstrate that co-operation from family members must
      be heavily relied upon.

PMID- 14685734
TI  - [Facial expression in severe dementia].
AB  - Little is known about emotions and facial expression in patients suffering from
      severe dementia. Therefore the facial expression of nine nursing home residents
      with severe dementia was videotaped in different emotionally relevant situations.
      The video clips were analyzed according to the Facial Action Coding System. The
      results show complex patterns of facial expression as well as individual patterns
      of facial movements.

PMID- 14685735
TI  - [Situations of emotional significance in residents suffering from dementia].
AB  - An advanced stage of dementia implies a loss of the ability to express emotions
      verbally. However, this does not mean that these patients do not feel emotions
      anymore. Analyses of nonverbal behaviour are the only way to realise the aim of
      assessing emotional states in people suffering from severe dementia. In the
      present study, we tried to identify characteristic situations which are regularly
      accompanied by positive or negative emotions. Such situations should be described
      by members of the institutional staff. Moreover, patients' nonverbal behaviour
      was analysed with psychological instruments developed for analyses of mimic
      expressions of emotion (FACS, EMFACS). Twenty-nine female residents of nursing
      homes suffering from moderate or severe dementia participated in the study.
      Nearly all of them were perceived to show different emotional states by the
      staff. Most emotions seemed to occur regularly in specific situations. Measures
      of FACS and AMFACS suggest that predictions of the staff are highly valid.
      Analyses of situations which were said to be accompanied by positive emotions
      showed that the respective situations are often created by the residents
      themselves. This finding implies that even an advanced stage of dementia does not
      necessarily prevent people from leading a self-determined life. Concentrated and
      individualised attention enables the staff to shape positive emotions in
      residents suffering from moderate or severe dementia.

PMID- 14685736
TI  - [Promotion and maintenance of independence in older people with intellectual
      disability-results of an intervention study].
AB  - Results of gerontological research have seldom been used for the development of
      new concepts for housing, promotion and supply in people with intellectual
      disability. However, recent findings from international studies support the
      assumption that capability to learn and plasticity are also apparent in people
      with intellectual disability. The present study was designed as an empirical test
      of this assumption. As a theoretical starting point we describe competence as a
      comprehensive construct which integrates aspects of independence, self
      responsibility, self-determination and experienced meaning of life. Moreover, the
      construct of competence refers to the impact of the physical, social, and
      infrastructural environment on the aforementioned aspects. We hypothesised that
      independent living in older people with intellectual disability could be enhanced
      by a more differentiated perception of respective potentials by the members of
      the institutional staff. An intervention program for caregivers was developed to
      initiate an examination of their own behaviour in daily interaction with
      intellectually disabled residents, particularly in terms of a possible support of
      dependent and ignorance of independent behaviour. We expected that unmasking
      contingencies between behaviour of care-givers and dependency in intellectual
      disabled residents should lead to increases in residents' independent behaviour
      and everyday competence. 40 intellectually disabled residents and 40 staff
      members participated in the present study. Videotapes were used to assess
      behaviour of staff members and residents in daily care and support. Moreover, a
      questionnaire was developed for further assessment of independence and everyday
      competence in intellectually disabled residents. Effects of the developed
      intervention program were tested with a pre-post-control group-design. Results
      show highly significant increases in residents' independence and everyday
      competence. Therefore, our hypothesis that independent living in older people
      with intellectual disability could be enhanced by a more differentiated
      perception of existing potentials by the members of the institutional staff
      received strong support.

PMID- 14685737
TI  - [Improvement of functional deficits, physical mobility and cognitive function by
      treatment in a geriatric day hospital].
AB  - OBJECTIVES AND METHODS: Several studies showed the efficacy of inpatient
      geriatric treatment. Different outcomes were reported for geriatric patients
      treated in outpatient facilities. To analyze the course of rehabilitation, 312
      patients (62.2% female) with a mean age of 77.2 years (SD = 7.4) in a geriatric
      day hospital were evaluated regarding a) changes of functional deficits and
      mobility, b) cognitive function and c) depression. Patients were examined with a
      geriatric assessment including activities of daily living, Tinetti, Timed-up and
      go, Mini Mental State Examination (MMSE), Clock Completion Test, Handgrip
      Strength-Test, Money-Counting Test and Geriatric Depression Scale (GDS) at
      admission and discharge. RESULTS: All examined parameters had changed
      significantly after treatment. A clear decrease in the portion of patients with
      disability-related outcomes in the examined parameters (Barthel Index, Tinetti,
      Timed-up and go, MMSE, GDS) was demonstrated: a) the proportion of patients with
      a Barthel Index under 75 had decreased by 26.5%, the proportion of patients with
      an increased risk of falls was reduced by 27%, b) the proportion of patients with
      a MMSE Score less than 24 was decreased by 14.8% and c) mild effects were
      achieved in depression. CONCLUSIONS: Day hospital geriatric treatment leads to an
      improvement of functional deficits, mobility and mental health of patients. The
      results contrast to other studies in day hospital treatment.

PMID- 14685738
TI  - [Changes in the quality of life of cerebral stroke patients in the first year
      after rehabilitation].
AB  - The aim of the study was to identify and analyze significant changes in the
      quality of life of elderly persons in the first year after rehabilitation from
      cerebral stroke. Data of 138 geriatric patients investigated on admission in a
      stationary rehabilitation program and one year later at home were used for this
      analysis. Multivariate logistic modelling tested differences between first
      investigation and follow-up in several domains: IADL functionality, subjective
      well-being, locus of control, subjective coping with stroke, stroke-related
      quality of life, social support. Age, gender, living alone and educational status
      were used as control variables. Compared to first investigation, subjects on
      follow-up showed an increased IADL functionality (OR = 1.40) but a decline in
      subjective well-being (OR = 0.91) and a more external locus of control (OR =
      0.57). Coping with stroke has ameliorated (OR = 1.82), while stroke-related
      quality of life in six life domains was more negatively presented (OR = 0.82).
      Marked modifications in social exchange were found: the quantity of social
      contacts increased (OR = 4.70), while their variety reduced (OR = 0.38),
      significant others became more important (OR = 7.42) while the respondents'
      importance as a significant person for others diminished (R = 0.20). The findings
      suggest that recovery in IADL functionality after rehabilitation does not ensure
      a subsequent improvement in the subjective well-being nor does a positive trend
      in coping with stroke impede declines in stroke-related quality of life.
      Increased social exchange, which becomes more concentrated and less reciprocal,
      indicates a growing need of receiving social support. The findings are commented
      and implications for rehabilitation are mentioned.

PMID- 14685747
TI  - Detection of coronary arterial microvascular disorders using (99m)Tc-tetrofosmin
      uptake increase during exercise and coronary blood flow velocity patterns
      obtained by magnetic resonance imaging.
AB  - This study reports an evaluation of coronary arterial blood flow patterns in
      patients with diabetes mellitus and healthy subjects using magnetic resonance
      coronary angiography (MRCA). Twenty patients with diabetes mellitus (DM group)
      and 20 healthy subjects (N group) were studied using MRCA and myocardial SPECT
      images using (99m)Tc-tetrofosmin (TF). The rate of change in myocardial TF uptake
      was measured during a 1-day protocol of exercise and rest. Initial and delayed
      exercise single photon emission computed tomography (SPECT) images were acquired
      30 min and 3 h after injection (370 MBq of TF) (TF1 and TF2, respectively).
      Thereafter, 740 MBq of TF was administered intravenously, again, and resting
      SPECT images (TF3) were acquired 30 min later. The myocardial counts of these
      three points of acquisition were defined, and the rate of change of myocardial TF
      uptake between exercise and rest was determined. The % increase in uptake was
      significantly lower in the DM group than in the N group in all myocardial
      segments. The average coronary arterial diastolic velocity determined using MRCA
      was slightly lower in the DM group than in the N group, and the average systolic
      peak velocity (ASPV) was slightly greater in the DM group than in the N group,
      although these values were not statistically significant. The diastolic/systolic
      velocity ratio (DSVR) in the DM group was significantly lower than that in the N
      group ( P < 0.05). There was a significant correlation between DSVR and % uptake
      increase ( r = 0.605, P < 0.05). These results indicate that the measurements
      made using MRCA and the % uptake increase measured using TF myocardial
      scintigraphy represent a potentially useful noninvasive method for diagnosing
      microvascular dysfunction in diabetic patients.

PMID- 14685748
TI  - Off-pump bypass grafting in patients with significant left main coronary artery
      stenosis.
AB  - The aim of this study was to investigate and determine whether patients with
      significant (> or = %50) left main coronary artery stenosis could undergo
      coronary bypass on the beating heart and compare the results to those obtained
      using the conventional method. Prospectively collected data of patients with
      significant left main coronary artery disease who had undergone coronary bypass
      on the beating heart (group A, n = 100) or with the conventional method (group B,
      n = 100) were evaluated retrospectively. EuroSCORE values, preoperative and
      operative details, postoperative morbidity and mortality, and early results were
      compared. Groups were similar in terms of EuroSCORE, demographics, and
      preoperative variables. Number of distal anastomoses per patient was 3.1 +/- 0.9
      in the beating heart group while it was 3.3 +/- 0.9 in the conventional group ( P
      = 0.09). Patients operated on with the conventional method had higher levels of
      peak creatine kinase-myocardial band, blood and blood product transfusions, and
      inotropic requirements, while mechanical ventilation times and hospital stay were
      longer. The incidence of postoperative atrial fibrillation, mediastinitis, and
      intra-aortic balloon usage were comparable between the groups. There was no
      neurological complication in group A whereas five major neurological
      complications (three transient ischemic attacks, two strokes) occurred in group B
      ( P = 0.06). Thirty-day mortality occurred in one patient in the beating heart
      group whereas five early deaths were observed in the conventional group ( P =
      0.21). In significant left main coronary artery stenosis coronary bypass on the
      beating heart is a safe and effective alternative to the conventional method with
      the same or better early results. The long-term results need to be evaluated.

PMID- 14685749
TI  - Prospective and randomized study of the antihypertensive effect and tolerability
      of three antihypertensive agents, losartan, amlodipine, and lisinopril, in
      hypertensive patients.
AB  - We prospectively evaluated the antihypertensive effect and tolerability of three
      different antihypertensive agents, losartan (angiotensin II receptor blocker),
      amlodipine (calcium channel blocker), and lisinopril (angiotensin-coverting
      enzyme inhibitor), in patients with mild-to-moderate hypertension. After a 2-week
      washout period, 121 patients were randomly allocated to three different groups
      for 12 weeks. Medications were titrated upward as necessary to achieve the goal
      office-recorded sitting diastolic blood pressure (SiDBP) (defined as SiDBP <90
      mmHg or SiDBP > or = 900 mmHg but with a > or = 10 mmHg drop from baseline).
      Efficacy and tolerability were assessed after 4, 8, and 12 weeks of therapy with
      each regimen. At 12 weeks, significant differences in SiDBP compared with data of
      baseline were noted in all three groups ( P < 0.001 in all comparisons).
      Similarly, significant differences in the sitting systolic blood pressure
      compared with baseline data were also seen for all three groups ( P < 0.001 in
      all comparisons). The number of patients reaching goal SiDBP were comparable for
      the three groups: 25 patients (62.5%) in the losartan group, 27 patients (67.5%)
      in the amlodipine group, and 22 patients (59.5%) in the lisinopril group (not
      significant). Amlodipine produced a more pronounced reduction in SiDBP than the
      other two medications, although without statistical significance. Patients
      receiving lisinopril showed a high incidence of coughing (31.7%). Low leg edema
      was noted only in the amlodipine group (7.5%). Compared with the amlodipine and
      lisinopril groups, the losartan group seemed to have relatively fewer episodes
      (7.5%), and fewer patients (three cases) experienced adverse effects. In
      conclusion, this study demonstrates that losartan has the same antihypertensive
      effect, but has superior tolerability compared with the other two drugs. Coughing
      was a common side effect of lisinopril therapy in our population.

PMID- 14685750
TI  - Clinical application of wave intensity for the treatment of essential
      hypertension.
AB  - Wave intensity analysis is a method of studying intravascular flow wave
      propagation, calculated as the product of the rate of change in pressure (d P/ t)
      and the rate of change in velocity (d U/d t). The typical pattern of wave
      intensity seen during the cardiac cycle has two dominant peaks. The larger first
      peak (FP) occurs during early systole when a forward traveling compression wave
      is generated by the left ventricle. The second smaller peak (SP) follows a period
      of relatively little net wave production during mid-systole. Wave reflection is
      seen as a small backward-traveling compression wave occurring just after the
      first peak of wave intensity (NP). In this study, we investigated the usefulness
      of parameters from the wave intensity for estimating the efficacy of the Alpha-1
      blocker, doxazosin, to reduce blood pressure, by the reduction of peripheral
      vascular resistance. We examined 20 patients with essential hypertension.
      Patients were included if their diastolic blood pressure was >95 mmHg on at least
      three separate visits to the clinic. The study consisted of a 2-week baseline
      phase followed by a 2-4-week dose-adjusted phase with doxazosin. Treatment began
      with 1 mg/day doxazosin, and the dose was doubled fortnightly until the diastolic
      blood pressure was <90 mmHg. Blood-pressure measurements and side effects were
      recorded at intervals of 2 weeks. Before and after 4 weeks of stable treatment
      with doxazosin, a comprehensive clinical evaluation was given. Doxazosin reduced
      systolic and diastolic blood pressure. Both FP and SP increased and NP decreased.
      DeltaMBP (change in mean blood pressure) correlated well with NP before and after
      the antihypertensive therapy. The efficacy of doxazosin was confirmed by the
      decreased reflection wave of aortic flow from wave intensity analysis. Thus,
      patients with a significant reflection wave may be good candidates for
      antihypertensive treatment by a vasodilator, such as doxazosin.

PMID- 14685751
TI  - Increased thrombolysis in myocardial infarction frame counts in patients with
      isolated coronary artery ectasia.
AB  - The Thrombolysis in Myocardial Infarction (TIMI) frame count is a simple clinical
      tool for assessing quantitative indexes of coronary blood flow. This measurement
      has been significantly correlated with flow velocity measured with a flow-wire by
      several investigators during baseline conditions or hyperemia. In this study we
      aimed to evaluate the coronary flow in patients with isolated coronary artery
      ectasia by means of the TIMI frame count and to compare the results with those of
      patients with angiographically normal coronary arteries. The study population
      consisted of 37 patients with coronary artery ectasia only in the right coronary
      artery (RCA). The control group consisted of 31 patients with angiographically
      proven normal coronary arteries. Coronary artery ectasia was defined as
      nonobstructive lesions of the coronary arteries with a luminal dilatation 1.5
      fold or more of the adjacent normal coronary segments. The TIMI frame count was
      determined for each major coronary artery in each patient according to the
      methods first described by Gibson et al. The TIMI frame count of RCA in the study
      group was significantly higher than in that of the control group (51 +/- 17 vs 25
      +/- 8, P < 0.0001). The TIMI frame counts of the study group for the left
      anterior descending and left circumflex coronary artery were also significantly
      higher than those of the control group (corrected TIMI frame count for LAD = 42
      +/- 11 vs 24 +/- 7, P < 0.001; TIMI frame count for LCx = 44 +/- 15 vs 25 +/- 9,
      P < 0.001). In patients with coronary artery ectasia, the TIMI frame count of the
      RCA was higher than that of the left anterior descending and left circumflex
      coronary artery (51 +/- 17 vs 42 +/- 11 and 44 +/- 15, respectively, P < 0.05).
      We have shown increased TIMI frame counts in patients with isolated coronary
      artery ectasia and suggest that the pathophysiological mechanism of coronary
      artery ectasia is not a focal disease. TIMI frame counts can be regarded as an
      index of the severity of impaired coronary flow in patients with coronary artery
      ectasia.

PMID- 14685752
TI  - The effect of pathophysiology on the outcome of mitral valve repair for mitral
      regurgitation.
AB  - The advantages of mitral valve repair in mitral regurgitation are well
      established. The aim of this study was to analyze retrospectively the early and
      mid-term results of primary mitral valve repair. Between January 1995 and August
      2001, primary mitral valve repair operations were performed on 112 patients (76
      men and 36 women) with mitral regurgitation; the mean age was 59.8 +/- 16.5
      years. Mitral valve repair was performed for rheumatic heart disease (13),
      degenerative disease (60), infective endocarditis (2), ischemic heart disease
      (26), congenital heart disease (2), and dilated cardiomyopathy (9). The degree of
      mitral regurgitation was moderate in 28 patients, moderately severe in 17
      patients, and severe in 67 patients, as determined by echocardiography. Left
      ventricular ejection fraction (mean 41.2% +/- 13.5%) was measured by radionuclide
      ventriculography. Fifty percent of patients underwent additional procedures
      (e.g., coronary artery bypass grafting). The mortality rate was 8.9% (10/112) for
      hospitalized patients, 19.2% (5/26) for ischemic disease, and 5% (3/60) for
      degenerative disease. Follow-up duration ranged from 0.37 to 84.03 months. All
      survivors were evaluated with serial echocardiography. At the final follow-up
      echocardiography of 94 patients without reoperation and 6 patients at the time of
      reoperation, 84% had no or mild mitral regurgitation. The survival rate at 5
      years was 92.68 +/- 3.57% for degenerative disease and 44.47% +/- 10.89% for
      ischemic disease. The risk of infective endocarditis (1.78%), thromboembolism
      (1.78%), and anticoagulant-related complications (0.8%) was very low during the
      follow-up period. The pathophysiological mechanism resulting in mitral
      regurgitation was the most important determinant of outcome after mitral valve
      repair. Excellent results were achieved with mitral valve repair for degenerative
      disease. Because of low morbidity and acceptable mortality, we strongly recommend
      mitral valve repair for mitral regurgitation due to degenerative disease.

PMID- 14685753
TI  - Effect of blood passage through the pulmonary circulation on fibrinolytic
      parameters.
AB  - The lung vasculature bed has a unique fibrinolytic potential, which has not yet
      been completely elucidated. We investigated the effect of blood passage through
      the pulmonary circulation on the values of fibrinolytic parameters in plasma.
      Forty-seven patients (16 women, 31 men, mean age 54 years, range 21-67 years) who
      had undergone elective cardiac catheterization were included in the study. The
      blood samples were taken simultaneously from the right atrium and the left
      ventricle. The following fibrinolytic parameters were measured: tissue-type
      plasminogen (t-PA) antigen and activity, plasminogen activator inhibitor-1 (PAI
      1) antigen and activity, and euglobulin clot lysis time (ECLT). No difference was
      found between the samples obtained from the right atrium and the left ventricle
      with respect to t-PA antigen: 8.1 (6.7-11.3) vs 8.4 (5.9-11.0) ng/ml; t-PA
      activity: 92 (5-680) vs 62 (32-696) IU/ml; PAI-1 antigen: 8.4 (5.5-14.3) vs 8.7
      (6.2-13.1) ng/ml; and ECLT: 5.5 (4.1-9.1) vs 5.6 (4.1-8.5) 1 000/min. In
      contrast, PAI activity decreased significantly: 7.9 (5.8-10.3) vs 7.4 (6.0-10.4)
      IU/ml, P < 0.01. Patients with and without pulmonary hypertension did not differ
      in any of measured parameters, either in the right atrium or in the left
      ventricle. These results show that under basal conditions fibrinolytic activity
      which is not attributed to t-PA is elevated in lung vasculature. Further, basal
      fibrinolytic activity in the lungs is not influenced by pulmonary hypertension.

PMID- 14685754
TI  - Clinical features and management of congenital long QT syndrome: a report on 54
      patients from a national registry.
AB  - To assess the clinical features and the management of congenital long QT syndrome
      (LQTS) in China, we collected the clinical data of 54 LQTS patients (14 males and
      40 females) from our newly established national registry. All patients were
      symptomatic, with syncope being the most common symptom. The average age when the
      first symptoms occurred was 17.9 +/- 15.6 (range, 0.5-62) years; 55.6% of them
      had the first symptoms before the age of 20. The most common triggers of the
      symptoms were physical exercise or emotional stress. The average corrected QT
      interval was 0.55 +/- 0.08 s. Using ECG criteria, there were 14 (25.9%) LQT1
      patients, 28 (51.9%) LQT2, and 2 (3.7%) LQT3. Thirty (55.6%) patients were
      treated with Beta-blockers at the time of enrollment, with propranolol being the
      most commonly used drug, with an average daily dose of 57.5 +/- 39.1 mg. Four
      patients underwent left cardiac sympathectomy. After an average follow-up of 24.9
      +/- 13.2 months, 3.1% (1/32) of patients with antiadrenergic therapy and 9.1%
      (2/22) without antiadrengergic therapy died of sudden cardiac death ( P < 0.05).
      We concluded that LQT2 might be the most common subtype in these patients.
      Antiadrenergic treatment was underused, raising the urgent need for educating
      both physicians and patients on the nature of the disease and its optimal
      antiadrenergic therapy.

PMID- 14685755
TI  - Effects of class I antiarrhythmic drugs on the digitalis-induced triggered
      activity arrhythmia model: a rationale for the short-term use of class I drugs
      against triggered arrhythmias.
AB  - Delayed afterdepolarization (DAD)-induced triggered activity has been considered
      to be one of the generation mechanisms of ventricular arrhythmias in the presence
      of intracellular Ca2+ overload. In this study, we analyzed the antiarrhythmic
      effects of class I antiarrhythmic drugs, namely, disopyramide, procainamide,
      mexiletine, and flecainide, on a recently developed DAD-induced triggered
      arrhythmia model, which consists of a canine ventricular septum preparation cross
      circulated with a blood-donor dog. After intravenous administration of ouabain to
      the donor dog, triggered arrhythmias were consistently induced in the cross
      circulated preparation by train stimulation (cycle length: 300 ms; train number:
      15). Intracoronary administration of disopyramide, procainamide, mexiletine, and
      flecainide as well as lidocaine suppressed the triggered arrhythmias at
      clinically relevant doses. Similar doses have been demonstrated to suppress
      intraventricular conduction in the same experimental model. These results suggest
      that the Na+ channel inhibition by class I drugs is an effective pharmacological
      intervention for suppressing Ca2+ overload, which may provide a rationale for the
      short-term use of class I drugs against the triggered arrhythmias in clinical
      practice.

PMID- 14685756
TI  - Unusual presentation of a pericardial cyst.
AB  - Pericardial cysts are rare abnormalities and usually do not cause any symptoms.
      Rarely, pericardial cysts cause symptoms and may lead to complications. There
      have been multiple case reports of rare complications of pericardial cysts
      including right ventricular outflow obstruction, pulmonary stenosis, pericardial
      tamponade, and partial erosion into the superior vena cava. We report a case of
      delayed presentation of a pericardial cyst following trauma causing a syndrome
      resembling congestive heart failure. To our knowledge there has been only one
      report of this complication.

PMID- 14685757
TI  - Two episodes of anuria and acute pulmonary edema in a losartan-treated patient
      with solitary kidney.
AB  - Atherosclerotic renal artery stenosis (RAS) is an increasingly important cause of
      end-stage kidney disease, and may cause hypertension, progressive renal failure,
      and recurrent pulmonary edema. Herein, we report two episodes of anuria and acute
      pulmonary edema associated with losartan treatment in a hypertensive patient with
      preexisting severe renal artery stenosis in a solitary kidney. After successful
      percutaneous renal balloon angioplasty procedure, urine flow was started
      immediately, despite 10 days of anuria. Blood pressure measurements were still at
      acceptable levels with a low dose Beta blocker, and serum creatinine levels were
      normal even after eight months. PTRA should be done in such patients, even with
      prolonged anuria. Physicians who recommend angiotensin receptor blockers in
      patients with RAS, especially in patients wih hypovolemia or a solitary kidney,
      should be careful about this complication.

PMID- 14685758
TI  - A giant left circumflex coronary artery--right atrium arteriovenous fistula
      detected by multislice spiral computed tomography.

PMID- 14685759
TI  - Osmotic, sodium, carbon dioxide and acid-base state of the Port Jackson shark,
      Heterodontus portusjacksoni, in response to lowered salinity.
AB  - In marine elasmobranch fish the consequences for CO2 and acid-base state of
      moving into low salinity water are not well described. Sub-adult Port Jackson
      sharks, Heterodontus portusjacksoni, occasionally enter brackish water and
      survive in 50% seawater (SW). The unidirectional Na efflux and content, plasma
      volume, glomerular filtration rate (GFR), body mass, as well as CO2 and acid-base
      state in H. portusjacksoni were investigated following transfer from 100% SW to
      75% SW and then to 50% SW. A rapid water influx resulted in a doubling of the
      plasma volume within 24 h in sharks in 75% SW and an 11% increase in body weight.
      Osmotic water influx was only partially offset by a doubling of the GFR. There
      was a approximately 40% decrease in plasma [Na] through a transiently elevated Na
      clearance and haemodilution. The result was a decrease in the inward gradient for
      Na+ together with reductions of nearly 50% in CO2 and buffer capacity. The sharks
      remained hypo-natric to 50% SW by partially conforming to the decrease in
      external osmotic pressure and avoided the need for active Na+ uptake. The
      gradient for Na+ efflux would by extrapolation approach zero at approximately 27%
      SW which may of itself prove a lethal internal dilution. In sharks transferred to
      75% SW, a small transient hypercapnia and a later temporary metabolic alkalosis
      were all largely explained through anaemia promoting loss of CO2 and buffer
      capacity. In sharks transferred to 50% SW the metabolic alkalosis persisted until
      the end of the 1-week trial. Within the erythrocytes, increased pH was consequent
      on the large decrease in haemoglobin content exhibited by the sharks, which
      caused a large reduction in intracellular buffer. In water as dilute as 50% SW
      there was no evidence of specific effects on the mechanisms of management of CO2
      or H+ excretion but rather significant and indirect effects of the severe
      haemodilution.

PMID- 14685760
TI  - Population variation in opsin expression in the bluefin killifish, Lucania
      goodei: a real-time PCR study.
AB  - Quantitative genetics have not been used in vision studies because of the
      difficulty of objectively measuring large numbers of individuals. Here, we
      examine the effectiveness of a molecular technique, real-time PCR, as an
      inference of visual components in the bluefin killifish, Lucania goodei, to
      determine whether there is population variation in opsin expression. Previous
      work has shown that spring animals possess a higher frequency of UV and violet
      cones and a lower frequency of yellow and red cones than swamp animals. Here, we
      found a good qualitative match between the population differences in opsin
      expression and those found previously in cone frequency. Spring animals expressed
      higher amounts of SWS1 and SWS2B opsins (which correspond to UV and violet
      photopigments) and lower amounts of RH2 and LWS opsins (which correspond to
      yellow and red photopigments) than swamp animals. The counterintuitive pattern
      between color pattern, lighting environment, and vision remains. Males with blue
      anal fins are more abundant in swamps where animals express fewer SWS1 and SWS2B
      opsins and where transmission of UV/blue wavelengths is low. Understanding this
      system requires quantitative genetic studies. Real-time PCR is an effective tool
      for studies requiring inferences of visual physiology in large numbers of
      individuals.

PMID- 14685761
TI  - Predictive medicine in urology.
AB  - Facing the limitations of financial resources available for health services, the
      necessity of evaluating new strategies in health management becomes evident.
      Experience from non-urological diseases suggests that prevention not only can
      reduce the number of incidences but also can be cost-effective. Predictive
      medicine or modern risk assessment could be a powerful tool to determine a given
      individual's risk for eventually developing the disease. A significant reduction
      in disease-related mortality as well as a reduction in costs can be expected if
      prevention and screening are focused on individuals at risk.

PMID- 14685763
TI  - Production of transgenic lily plants by Agrobacterium-mediated transformation.
AB  - A system for the production of transgenic plants was developed for the Oriental
      hybrid lily, Lilium cv. Acapulco, by Agrobacterium-mediated genetic
      transformation. Filament-derived calli were co-cultivated with A. tumefaciens
      strain EHA101/pIG121Hm, which harbored a binary vector carrying the neomycin
      phosphotransferase II, hygromycin phosphotransferase, and intron-containing beta
      glucuronidase genes in the T-DNA region. Six hygromycin-resistant (Hyg(r))
      culture lines were obtained from 200 calli by scratching them with sandpaper
      prior to inoculation and using NH(4)NO(3)-free medium for co-cultivation and a
      hygromycin-containing regeneration medium for selection. Hyg(r) culture lines
      regenerated shoots, which developed into plantlets following transfer to a plant
      growth regulator-free medium. All of these plantlets were verified to be
      transgenic by GUS histochemical assay and inverse PCR analysis.

PMID- 14685762
TI  - The association between smoking, beverage consumption, diet and bladder cancer: a
      systematic literature review.
AB  - In this paper the association between smoking history, beverage consumption, diet
      and bladder cancer incidence is systematically reviewed. A rating system has been
      used to summarise the level of scientific evidence (i.e. convincing, probable,
      possible, and no evidence) and the level of association (i.e. substantially
      increased, (RR> or =2.5), moderately increased (1.5< or =RR<2.5), slightly
      increased (1.2< or =RR<1.5), no association (0.8< or =RR<1.2), slightly decreased
      (0.7< or =RR<0.8), moderately decreased (0.4< or =RR<0.7), and substantially
      decreased (RR<0.4)). There is convincing evidence that cigarette smoking status,
      frequency and duration substantially increase the risk of bladder cancer.
      However, the evidence is not clear for other forms of smoking. A small increased
      risk for cigar, pipe, and environmental smoking is only possible. There is
      possible evidence that total fluid intake is not associated with bladder cancer.
      Although there is convincing evidence for a positive association between alcohol
      consumption and bladder cancer risk in men, the risk is small and not clinically
      relevant. Coffee and tea consumption are probably not associated with bladder
      cancer. The authors conclude that total fruit consumption is probably associated
      with a small decrease in risk. There is probably no association between total
      vegetable intake, vitamin A intake, vitamin C intake and bladder cancer and a
      possibly moderate inverse association with vitamin E intake. Folate is possibly
      not associated with bladder cancer. There probably is a moderate inverse
      association between selenium intake and bladder cancer risk.

PMID- 14685764
TI  - In vitro androgenesis in apple--improvement of the induction phase.
AB  - Based on a protocol for microspore culture in apple ( Malus domestica Borkh.),
      the embryo induction phase has been improved with regard to pretreatment of
      microspores for initiation of microspore embryogenesis, the concentration of
      carbon source in the induction medium and the microspore density in the
      suspension. Furthermore, the effect of the genotype was studied. To determine the
      efficiency of in vitro androgenesis, both methods, via anther and microspore
      culture, were investigated using the same bud material. A comparison of the
      efficiency of embryo induction in anther and microspore cultures showed that
      microspore culture resulted in an increase up to 10 times, depending on the
      genotype. The regeneration route in microspore culture is similar to that of
      androgenic embryos via anther culture and showed adventitious shoot formation in
      most cases after a long period of secondary embryogenesis.

PMID- 14685766
TI  - Fungal proteomics: initial mapping of biological control strain Trichoderma
      harzianum.
AB  - Trichoderma harzianum is a soil-borne filamentous fungus that exhibits biological
      control properties. T. harzianum can prevent the growth of pathogenic fungi on
      many types of plant crops, providing a chemically benign alternative to
      fungicidal agents currently on the market. A proteomic approach was taken to
      separate and identify proteins from a strain of T. harzianum with well
      established biocontrol properties. We developed a method of extracting proteins
      under acidic conditions that increased the solubilisation of alkaline proteins
      and eliminated acidic cell wall artefacts from micro-organisms in general.
      Combined with the use of protease inhibitors, this sample preparation method
      resulted in hundreds of proteins from T. harzianum being extracted and separated
      by two-dimensional gel electrophoresis. Proteins were identified by a combination
      of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry
      and liquid chromatography mass spectrometry (LC MS/MS). Manual de novo sequencing
      was conducted to obtain sequence tags on unidentified proteins. A total of 25
      protein spots were positively identified from a whole-cell protein reference map
      of T. harzianum.

PMID- 14685765
TI  - Regulation of glycolysis in Kluyveromyces lactis: role of KlGCR1 and KlGCR2 in
      glucose uptake and catabolism.
AB  - In Kluyveromyces lactis, the casein kinase I (Rag8p) regulates the transcription
      of glycolytic genes and the expression of the low-affinity glucose transporter
      gene RAG1. This control involves the transcription factor Sck1p, a homologue of
      Sgc1p of Saccharomyces cerevisiae. SGC1 is known to interact genetically with
      ScGCR1 and ScGCR2, which code for regulators of glycolytic gene expression.
      Therefore, we studied the role of KlGCR1 and KlGCR2 genes in K. lactis. The
      Klgcr1 null mutant could not grow on glucose when respiration was blocked by
      antimycin A (Rag(- )phenotype). In contrast, the Klgcr2 null mutant could grow
      under the same conditions, although at a reduced rate. In both mutants, the
      transcription of glycolytic genes was affected, while that of ribosomal protein
      genes was not modified. Furthermore, the transcription of the glucose permease
      genes was also found to be affected in the two mutants, although dissimilarly.
      While RAG1 transcription decreased at high glucose concentrations, the expression
      of the high-affinity glucose permease gene HGT1 was unexpectedly impaired under
      gluconeogenic conditions, in the absence of glucose. Gel mobility shift assays
      performed with purified maltose-binding protein-KlGcr1p showed that KlGcr1p could
      interact directly with the promoters of the glycolytic genes, but not with the
      promoters of the glucose permease genes. Thus, the control exerted by KlGcr1p and
      KlGcr2p upon glucose transporter genes is probably indirect.

PMID- 14685767
TI  - Transcriptional activators Cat8 and Sip4 discriminate between sequence variants
      of the carbon source-responsive promoter element in the yeast Saccharomyces
      cerevisiae.
AB  - The structural genes for gluconeogenesis in the yeast Saccharomyces cerevisiae
      are activated by the carbon source-responsive element (CSRE) found in the
      respective upstream regions. Regulatory genes CAT8 and SIP4 both encode zinc
      cluster proteins which can bind to CSRE motifs and activate target genes under
      conditions of glucose deprivation. In this work, we describe a functional
      analysis of sequence variants containing single mutations within the strongly
      activating CSRE(ICL1) motif. While the sequence CCNNNNNNCCG was required as the
      minimal UAS for gene activation by both Cat8 and Sip4, the activators responded
      differently to sequence variations in the central part of the CSRE. Our results
      allowed us to derive a consensus sequence for efficient gene activation by Cat8
      (YCCNYTNRKCCG), while a more specific motif is required for activation by Sip4
      (TCCATTSRTCCGR). Although their zinc cluster domains are clearly related, Cat8
      and Sip4 are not isofunctional. This conclusion is further supported by the
      finding that biosynthetic derepression of Cat8 in the presence of a
      nonfermentable carbon source precedes that of Sip4 by about 90 min.

PMID- 14685768
TI  - Regulation of two homodimer hexosaminidases in the mycoparasitic fungus
      Trichoderma asperellum by glucosamine.
AB  - Trichoderma asperellum is a mycoparasitic fungus which is used as a biocontrol
      agent against plant pathogens. Its hydrolytic enzymes take part in its parasitic
      interaction, degrading the pathogen cell wall and thereby helping to control
      disease. One of those enzymes, beta- N-acetyl- d-glucosaminidase (GlcNAcase),
      degrades chitin, which is a major component of the cell wall of many plant
      pathogenic fungi. Two GlcNAcases of T. asperellum T203, designated EXC1Y and
      EXC2Y, were purified, their genes and their promoters were sequenced, and their
      regulation was studied. The enzymes share homology (59% identity) but are easily
      distinguished by PAGE assay. Biochemical characterization, Edman degradation, and
      mass spectrometry demonstrated that EXC1Y and EXC2Y are both active as
      homodimers. Both genes are up-regulated by glucosamine (GlcN), in contrast to two
      endochitinases of this fungus. GlcN induces the secretion of several proteins
      (including a beta-glucosidase), among which EXC1Y is the most abundant. An exc2y
      knockout was constructed, to study the regulation of EXC1Y expression and
      secretion. The fungus has the ability to store a high amount of this enzyme in an
      active form and secrete it into the medium later.

PMID- 14685769
TI  - Quantifying BSE control by calculating the basic reproduction ratio R0 for the
      infection among cattle.
AB  - The safety of using meat and bone meal (MBM) in mammal feed was studied in view
      of BSE, by quantifying the risk of BSE transmission through different infection
      routes. This risk is embodied in the basic reproduction ratio R(0) of the
      infection, i.e. the average number of new infections induced by one initial
      infection. Only when R(0) is below 1, will the disease die out with certainty and
      the population will become free from BSE. Unfortunately this is a slow process
      due to the slow progression of the disease. We calculate R(0) explicitly from
      basic ingredients taking several different transmission routes into account.
      Several of the basic ingredients are functions of age or of infection-age. We
      also calculate the exponential growth rate r in terms of the same basic
      ingredients. Next we quantify the ingredients from available data and compute the
      effects on R(0) of various scenario's for controlling BSE, with examples for the
      UK and the Netherlands.

PMID- 14685770
TI  - Stochastic models for cell motion and taxis.
AB  - Certain biological experiments investigating cell motion result in time lapse
      video microscopy data which may be modeled using stochastic differential
      equations. These models suggest statistics for quantifying experimental results
      and testing relevant hypotheses, and carry implications for the qualitative
      behavior of cells and for underlying biophysical mechanisms. Directional cell
      motion in response to a stimulus, termed taxis, has previously been modeled at a
      phenomenological level using the Keller-Segel diffusion equation. The Keller
      Segel model cannot distinguish certain modes of taxis, and this motivates the
      introduction of a richer class of models which is nevertheless still amenable to
      statistical analysis. A state space model formulation is used to link models
      proposed for cell velocity to observed data. Sequential Monte Carlo methods
      enable parameter estimation via maximum likelihood for a range of applicable
      models. One particular experimental situation, involving the effect of an
      electric field on cell behavior, is considered in detail. In this case, an
      Ornstein- Uhlenbeck model for cell velocity is found to compare favorably with a
      nonlinear diffusion model.

PMID- 14685771
TI  - Dynamics of one-dimensional spiking neuron models.
AB  - In this paper we make a rigorous mathematical analysis of one-dimensional spiking
      neuron models in a unified framework. We find that, under conditions satisfied in
      particular by the periodically and aperiodically driven leaky integrator as well
      as some of its variants, the spike map is increasing on its range, which leaves
      no room for chaotic behavior. A rigorous expression of the Lyapunov exponent is
      derived. Finally, we analyse the periodically driven perfect integrator and show
      that the restriction of the phase map to its range is always conjugated to a
      rotation, and we provide an explicit expression of the invariant measure.

PMID- 14685772
TI  - Permanence of discrete-time Kolmogorov systems for two species and saturated
      fixed points.
AB  - This paper considers the dynamics of a discrete-time Kolmogorov system for two
      species populations. In particular, permanence of the system is considered.
      Permanence is one of the concepts to describe the species' coexistence. By using
      the method of an average Liapunov function, we have found a simple sufficient
      condition for permanence of the system. That is, nonexistence of saturated
      boundary fixed points is enough for permanence of the system under some
      appropriate convexity or concavity properties for the population growth rate
      functions. Numerical investigations show that for the system with population
      growth rate functions without such properties, the nonexistence of saturated
      boundary fixed points is not sufficient for permanence, actually a boundary
      periodic orbit or a chaotic orbit can be attractive despite the existence of a
      stable coexistence fixed point. This result implies, in particular, that
      existence of a stable coexistence fixed point is not sufficient for permanence.

PMID- 14685773
TI  - Quasi-steady state assumptions for non-isolated enzyme-catalysed reactions.
AB  - The nature and validity of the mathematical formulation of Michaelis-Menten type
      kinetics for enzyme-catalysed biochemical reactions is studied. Almost all
      previous work has concentrated on isolated reactions, i.e. those without input or
      other environmental influences. In this paper, we investigate the effects of
      substrate input on this formulation, in particular, on the nature and validity of
      the quasi-steady state assumptions.

PMID- 14685774
TI  - A macroscopic approach to demography.
AB  - A canonical/lognormal model for human demography is established, specifying the
      net maternity function and the age distribution for mothers of new-borns using a
      single macroscopic parameter vector of dimension five. The age distribution of
      mothers is canonical, while the net maternity function normalizes to a lognormal
      density. Comparison of an actual population with the model serves to identify
      anomalies in the population which may be indicative of phase transitions or
      influences from levels outside the demographic. Tracking the time development of
      the parameter vector may be used to predict the future state of a population, or
      to interpolate for data missing from the record. In accordance with classical
      theoretical considerations of Backman, Prigogine, et al., it emerges that the
      logarithm of a mother's age is the most fundamental time variable for demographic
      purposes.

PMID- 14685775
TI  - 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine
      (VNP40101M): II. Role of O6-alkylguanine-DNA alkyltransferase in cytotoxicity.
AB  - PURPOSE: VNP40101M (1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2
      [(methylamino)carbonyl]hydrazine) is a sulfonylhydrazine prodrug that possesses
      broad spectrum antitumor efficacy in murine models. VNP40101M activation
      generates chloroethylating species that alkylate DNA at the O(6)-position of
      guanine, and a carbamoylating agent, methyl isocyanate, which inhibits O(6)
      alkylguanine-DNA alkyltransferase (AGT) in model systems. We determined whether
      expression of AGT in Chinese hamster ovary (CHO) cells decreased sensitivity to
      VNP40101M and explored the mechanism of VNP40101M cytotoxicity by employing
      analogs of VNP40101M that generate reactive intermediates with either
      carbamoylating or chloroethylating activity. METHODS: AGT was overexpressed in
      CHO cells by transfection with an expression vector containing the human AGT
      gene. Cell lines expressing AGT were employed in clonogenic assays to determine
      the cytotoxicity of VNP40101M and its analogs. RESULTS: VNP40101M was more active
      against AGT-expressing CHO cells than 90CE (1,2-bis(methylsulfonyl)-1-(2
      chloroethyl)hydrazine), a chloroethylating generator devoid of carbamoylating
      activity. Furthermore, the greater the degree of AGT expression the more
      resistance to VNP40101M cytotoxicity. Combination chemotherapy experiments
      support the conclusions that methyl isocyanate and the chloroethylating species
      generated from the activation of VNP40101M function synergistically to kill
      cells. CONCLUSIONS: The findings support the concept that alkylation of the O(6)
      position of guanine residues in DNA is the predominant lesion created by
      VNP40101M, and that methyl isocyanate resulting from the base-catalyzed
      activation of VNP40101M inhibits AGT and presumably other enzymes involved in DNA
      repair, thereby enhancing the yield of the DNA G-C interstrand crosslinks
      responsible for the antitumor activity of this agent.

PMID- 14685778
TI  - Dendritic cells loaded with exogenous antigen by electroporation can enhance MHC
      class I-mediated antitumor immunity.
AB  - To develop an efficient antitumor immunotherapy, we have examined if dendritic
      cells (DCs) loaded with soluble antigens by electroporation present more antigens
      via the MHC (major histocompatibility complex) class I pathway, which mediate a
      cytotoxic T-cell response. DCs loaded with ovalbumin (OVA) by electroporation
      presented more MHC class I-restricted determinants compared with DCs pulsed with
      OVA. When electroporated DCs were pulsed with OVA for additional times, both MHC
      class I- and II-restricted presentation of OVA were increased compared with each
      single procedure, including electroporation or simple pulse. Immunization with
      DCs loaded with OVA by electroporation induced higher cytotoxicity of splenocytes
      to E.G7 cells, a clone of EL4 cells transfected with an OVA cDNA, than
      immunization with DCs pulsed with OVA. In the animal study, immunization with DCs
      loaded with OVA or tumor cell lysates by electroporation induced an effective
      antitumor immunity against tumor of E.G7 cells or Lewis lung carcinoma cells,
      respectively. In addition, immunization with DCs loaded with antigen by
      combination of electroporation and pulse, completely protected mice from tumor
      formation, and prolonged survival, in both tumor models. These results
      demonstrated that electroporation would be a useful way to enhance MHC class I
      mediated antitumor immunity without functional deterioration, and that the
      combination of electroporation and pulse could be a simple and efficient antigen
      loading method and consequently lead to induction of strong antitumor immunity.

PMID- 14685779
TI  - Dendritic cell biology and cancer therapy.
AB  - Dendritic cells (DCs) are nature's best antigen-presenting cells. They possess
      attributes that allow them to effectively fulfill the requirements for
      priming/activating T cells and mediating tumor-specific immune responses. In this
      review, emphasis is placed on those aspects of DC biology that best illustrate
      their usefulness in immunotherapy of cancer. Culture, maturation, and
      polarization conditions for human DC are discussed, as are strategies for antigen
      loading of DCs and for their delivery to patients with cancer. A concise
      recommendation for monitoring of DC-based vaccination trails is provided.

PMID- 14685780
TI  - Tumour escape: antitumour effectors too much of a good thing?
AB  - Although even "spontaneous" tumours are immunogenic and are commonly infiltrated
      by tumour antigen-specific T cells (at least in melanoma), most tumours are not
      completely rejected by the host, and cancer progresses. There is a growing
      realisation that many responses defined as antitumour effector mechanisms act as
      double-edged swords and under different conditions either become ineffective or
      even protumorigenic. Examples are interleukin 2 (also proapoptotic for activated
      T cells), interferon gamma (by induction of ligands for T and NK cell inhibitory
      receptors), angiogenesis inhibition (by hypoxia-mediated induction of growth
      factors promoting metastasis), and macrophage free radical-mediated cytotoxicity
      (by inhibiting T cells). Immune selection pressure itself, resulting in outgrowth
      of resistant tumour variants could also be viewed in this light. On the other
      hand, knowledge of the many tumour escape pathways offers the theoretical
      possibility of reconstituting antitumour immunity. Tumour escape from
      immunosurveillance represents the last series of hurdles to be overcome in
      formulating truly effective cancer immunotherapy, but given the immense
      plasticity of the tumour cell, and the complex balance between pro- and
      antitumour activity of the very same effector pathways, this remains a major
      challenge.

PMID- 14685781
TI  - Immunobiology of HER-2/neu oncoprotein and its potential application in cancer
      immunotherapy.
AB  - HER-2/neu (also known as HER2 or c-erb-B2) is a 185-kDa protein receptor with
      tyrosine kinase activity and extensive homology to the epidermal growth factor
      (EGF) receptor. HER-2/neu is expressed in many epithelial tumors and known to be
      overexpressed in approximately 20-25% of all ovarian and breast cancers, 35-45%
      of all pancreatic adenocarcinomas, and up to 90% of colorectal carcinomas. HER
      2/neu overexpression represents a marker of poor prognosis. HER-2/neu-positive
      tumor cells are potentially good targets for tumor-reactive cytotoxic T
      lymphocytes which have been utilized in immunotherapeutic trials. In addition,
      the "humanized" monoclonal antibody Herceptin has been tested in several clinical
      trials and proved to be an effective adjuvant therapy for HER-2/neu-positive
      breast and ovarian cancers. Vaccinations aiming at generating T-cell responses
      are being examined in both experimental and clinical trials. Natural immunity at
      the level of T and B cells has been observed in patients with HER-2/neu-positive
      tumors confirming the immunogenicity of HER-2/neu and encouraging vaccination
      trials with HER-2 protein-derived subunits or synthetic peptides. This review
      summarizes recent data from patients with various types of HER-2/neu
      overexpressing cancers carrying different HLA alleles and exhibiting preexistent
      immunity to HER-2/neu-derived synthetic peptides. It also discusses potential
      advantages of the various vaccination approaches to immunotherapy targeting the
      HER-2/neu molecule.

PMID- 14685782
TI  - Natural killer lymphocytes: biology, development, and function.
AB  - Natural killer (NK) lymphocytes represent the first line of defense against
      virally infected cells and tumor cells. The role of NK cells in immune responses
      has been markedly explored, mainly due to the identification of NK cell receptors
      and their ligands, but also through the analysis of mechanisms underlying the
      effects of various cytokines on NK cell development and function. A population of
      lymphocytes that shares function and receptors with NK cells is represented by
      natural killer T (NKT) cells. NKT lymphocytes are regulators of both innate and
      adaptive immune responses, but have also been reported to function as effector
      antitumor cells. The marked progress in our understanding of the biology,
      development, and function of NK/NKT cells has provided the basis for their
      potential application in tumor clinical trials.

PMID- 14685783
TI  - Monitoring of a new approach of immunotherapy with allogenic (111)In-labelled NK
      cells in patients with renal cell carcinoma.
AB  - The transfusion of allogenic, in vitro expanded natural killer cells (NKC) is a
      novel therapy option in oncology. To date, however, the biodistribution and
      kinetics of allogenic NKC have not been investigated. Therefore, in this study
      three patients with renal cell carcinoma received 3-7 x 10(8) NKC labelled with
      indium-111 oxine with a tenfold excess of unlabelled cells during NKC therapy.
      Whole-body scintigrams were obtained (0.5-144 h) in the anterior and posterior
      views. Scintigrams were analysed using a region of interest technique, and single
      photon emission tomography (SPET) studies of the abdomen were performed. Results
      were compared to those obtained with polymerase chain reaction (PCR) of the
      peripheral blood (determination of foreign DNA, nested PCR, limit of detection
      0.01%). Shortly after transfusion of NKC, more than 50% of the activity was
      accumulated in the lungs. We observed redistribution effects from lungs to liver,
      spleen and bone marrow. No significant loss of activity could be detected. In two
      of four large metastases, tracer accumulation could be proven by SPET. As
      confirmed by scintigrams and PCR, the fraction of circulating transfused cells
      was low at all times. Long-term activity retention might be caused either by
      survival of the allogenic cells, as confirmed by PCR (up to 3 days p.i.), or by
      phagocytosis of labelled cellular fragments. However, PCR data and uptake in
      metastases indicated long survival of a portion of allogenic NKC. Such long
      survival and low retention of the cells in the lung are requirements for an
      effective immunotherapeutic approach.

PMID- 14685785
TI  - Degradation of 2-fluorophenol by the brown-rot fungus Gloeophyllum striatum:
      evidence for the involvement of extracellular Fenton chemistry.
AB  - Iron-containing liquid cultures of the brown-rot basidiomycete Gloeophyllum
      striatum degraded 2-fluorophenol. Two simultaneously appearing degradation
      products, 3-fluorocatechol and catechol, were identified by gas chromatography
      and mass spectrometry (GC-MS). Concomitantly, fluoride was produced at
      approximately 50% of the amount that theoretically could be achieved upon
      complete dehalogenation. Defluorination was strongly inhibited in the presence of
      either the hydroxyl radical scavenger mannitol or superoxide dismutase, as well
      as in the absence of iron. The addition of the natural iron chelator oxalate
      caused a clear but less extensive inhibition, whereas supplementation with the
      artificial iron chelator nitrilotriacetic acid increased fluoride production.
      Extracellular 2-fluorophenol degradation was evidenced by defluorination,
      observed upon addition of 2-fluorophenol to cell-free culture supernatants
      derived from iron-containing fungal cultures. Ultrafiltered culture supernatants
      oxidized methanol to formaldehyde, known as a product of the reaction of methanol
      with hydroxyl radical. In addition, G. striatum was found to produce metabolites
      extractable with ethyl acetate that are capable of reducing Fe3+. GC-MS analysis
      of such extracts revealed the presence of several compounds. The mass spectrum of
      a prominent peak matched those previously reported for 2,5-dimethoxyhydroquinone
      and 4,5-dimethoxycatechol, fungal metabolites implicated to drive hydroxyl
      radical production in Gloeophyllum. Taken together, these findings further
      support an extracellular Fenton-type mechanism operative during halophenol
      degradation by G. striatum.

PMID- 14685786
TI  - Detection and quantitative estimation of Dehalococcoides spp. in a dechlorinating
      bioreactor by a combination of fluorescent in situ hybridisation (FISH) and
      kinetic analysis.
AB  - The unique capacity of Dehalococcoides ethenogenes of completely dechlorinating
      the common groundwater pollutant tetrachloroethene (PCE) to the harmless ethene
      makes this microorganism very attractive for application in natural or engineered
      bioremediation systems. In this study, the qualitative and quantitative
      determination of Dehalococcoides spp. in a lab-scale bioreactor was performed
      based on the combination of fluorescent in situ hybridisation (FISH) for specific
      detection, and kinetic batch tests at non-limiting hydrogen and PCE concentration
      for quantitative determination. The dechlorinating bioreactor was operated at a
      high and constant PCE loading rate of 255 micromol PCE [g volatile suspended
      solids (VSS)](-1) day(-1). Pale coccoid cells resembling the distinctive
      morphotype of D. ethenogenes were present in the microbial culture. These cocci
      hybridised with both eubacterial probes and the Dhe1259t probe recently designed
      for detecting Dehalococcoides spp. Positive hybridisation was also observed when
      the DHC1377 reverse primer was used as a specific probe and applied to the
      dechlorinating microbial consortium. The maximum dechlorination rate obtained
      under non-limiting hydrogen and PCE concentrations was 3.22 +/- 0.08 mmol Cl(-)
      l(-1 )day(-1). From the specific activity of D. ethenogenes [i.e. 0.055 +/- 0.008
      mmol Cl(-) (mg VSS)(-1) day(-1)], as reported from pure culture study, this
      observed maximum rate corresponded to a concentration of this bacterium in the
      mixed liquor of the bioreactor of 59.0+/-10.4 mg VSS.l(-1) (41.5+/-11.2% of
      overall VSS). This calculated relative abundance of D. ethenogenes was in
      agreement with the percentage of methanol (in terms of reducing equivalents)
      channeled to reductive dechlorination (approximately 30%) supporting the
      assumption that most reductive dechlorination was actually due to this
      microorganism.

PMID- 14685787
TI  - Effective extracellular trehalose production by Cellulosimicrobium cellulans.
AB  - A bacterium isolated from a petal of Casa Blanca Lily (ST26 strain) produced a
      marked amount of extracellular trehalose (alpha- d-glucopyranosyl-[1,1]-alpha- d
      glucopyranose) in culture medium containing glucose. 16S rDNA-based phylogeny
      showed that ST26 belongs to, or is related to, Cellulosimicrobium cellulans, a
      close relative of Cellulomonas spp. Various Cellulomonas strains obtained from
      culture collections also showed extracellular trehalose productivity, suggesting
      that trehalose production is a common property of this bacterial genus. ST26
      accumulated trehalose in medium supplied with glucose but not with sucrose,
      glycerol or maltose. Effective extracellular trehalose production by ST26 was
      achieved by supplying 0.5-1% ammonium sulfate and 0.5-1% CaCO(3). The addition of
      CaCO(3) adjusted the pH of the culture to around 5.0. The optimized culture
      conditions yielded trehalose from glucose at a conversion rate of 61%. The
      addition of ammonium sulfate greatly reduced the dry cell weight of ST26 and
      intracellular content of trehalose, which suggests that the addition of ammonium
      sulfate makes ST26 cells leak trehalose into the medium. ST26 effectively
      propagated in minimal medium containing trehalose as a sole carbon source, which
      suggests that trehalose serves as a carbohydrate reserve of this organism.

PMID- 14685788
TI  - Meconium periorchitis--a rare cause of a paratesticular mass.
AB  - We report a 9-month-old boy who presented with a hard paratesticular mass.
      Clinical and ultrasound findings were highly suggestive of malignancy and
      orchidectomy was performed. Histology confirmed the unexpected diagnosis of
      meconium periorchitis, a rare, benign condition resulting from intrauterine bowel
      perforation.

PMID- 14685789
TI  - Congenital intrahepatic arterioportal and portosystemic venous fistulae with
      jejunal arteriovenous malformation depicted on multislice spiral CT.
AB  - We report a symptomatic infant with very rare congenital arterioportal and
      portosystemic venous fistulae in the liver. Multislice CT after partial
      transcatheter embolisation revealed not only the complicated vascular
      architecture of the lesion, but also an incidental jejunal arteriovenous
      malformation which explained the patient's melena. The patient underwent ligation
      of the hepatic artery and resection of the jejunal arteriovenous malformation.
      Postoperative multislice CT clearly demonstrated the success of the treatment.

PMID- 14685790
TI  - Early Doppler changes in a renal transplant patient secondary to abdominal
      compartment syndrome.
AB  - Physiologic changes in renal transplant patients, such as transiently low central
      venous pressure, may be related to increased intra-abdominal pressure, from the
      volume of the transplanted kidney itself. Using intraoperative and postoperative
      Doppler ultrasound of the transplant renal vessels, we identified changes in flow
      dynamics following closure of the abdomen and reversal of the changes when the
      abdomen was reopened. This was attributed to abdominal compartment syndrome and a
      fasciotomy was created in the abdominal wall to accommodate the transplanted
      kidney. The findings in this case, in keeping with abdominal compartment
      syndrome, are not often considered in transplant recipients, but may explain some
      of the postsurgical physiology in some patients, particularly in the pediatric
      population.

PMID- 14685792
TI  - The value of ultrasound examination of the lungs in predicting bronchopulmonary
      dysplasia.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is one of the most serious
      complications of neonatal mechanical ventilation. Early diagnosis may influence
      treatment options such as early steroid administration. OBJECTIVE: To assess the
      role of US of the lungs in predicting the development of BPD in infants with
      hyaline membrane disease (HMD) and to determine the earliest possible age at
      which the diagnosis of BPD could be made with certainty. PATIENTS AND METHODS:
      Consecutive premature newborn infants requiring assisted ventilation during 1997
      1998 who were admitted because of HMD were studied prospectively. US of the lungs
      was performed within 3 days of birth and three times a week thereafter until
      discharge from the neonatal intensive care unit. Each patient was also clinically
      and radiographically evaluated for the presence or absence of BPD at day 28 of
      life. Lung US scans were correlated with the development of BPD. RESULTS:
      Retrodiaphragmatic hyperechogenicity (RH) was initially observed in 28 of the 36
      patients with HMD, but resolved completely in 24 (96%) of 25 infants who had an
      uncomplicated clinical course. In eight of the ten infants who developed BPD, RH
      persisted. Day 9 was the earliest day where persistence of abnormal RH was
      observed with the highest predictor values for the development of BPD.
      CONCLUSIONS: Lung US is a valuable technique for predicting the development of
      BPD.

PMID- 14685795
TI  - Penile apoptosis in association with p53 under lack of testosterone.
AB  - It is known that testosterone deficiency induces apoptosis in the prostate and
      that p53 protein is involved in this apoptosis. Therefore, p53 protein may also
      be involved in apoptosis induction in a testosterone-deficient state in the
      penis. In this study, we investigated whether castration and chemical castration
      induce apoptosis at penile tissue in rats, and whether p53 protein is involved in
      this apoptosis. Male SD rats aged 8 weeks were divided into four groups: 1) the
      Control group; 2) the Castration group; 3) the Estrogen group, in which rats
      received betaestradiol 17-(beta-D-glucuronide) injection of 500 microg/body/day;
      and 4) the LH-RH group, in which rats received LH-RH analogue (leuprorelin
      acetate) injection of 2 mg/kg. The rats were sacrificed after treatment on days
      1, 3, 5, 14, and 28 by cervical dislocation. Apoptotic cells and p53 protein
      positive cells were observed on the 5th day after treatment and thereafter in all
      castration, estrogen, and LH-RH groups. These findings showed that both
      castration and chemical castration induced p53 protein in vascular endothelial
      cells in the corpus cavernosus during the process of losing testosterone. It was
      also suggested that in such states, apoptosis is induced in vascular endotherial
      cells in the corpus cavernosus.

PMID- 14685796
TI  - Comparison of the nuclear matrix protein 22 with voided urine cytology in the
      diagnosis of transitional cell carcinoma of the bladder.
AB  - Several urinary markers for transitional cell carcinoma have been investigated,
      including urine cytology, bladder tumor antigen, autocrine motility factor
      receptor and fibrin degradation products. Unfortunately, they have poor overall
      sensitivity. The United States Food and Drug Administration have recently
      approved nuclear matrix protein (NMP 22) for the detection of occult or rapidly
      recurring disease after transurethral resection of bladder tumor. The objective
      of the current study was to assess the sensitivity of NMP 22 for the detection of
      bladder carcinoma, as well as to correlate the NMP 22 values with multiplicity of
      tumor, tumor size, configuration, stage and grade respectively. A total of 78
      patients (38 with bladder cancer) provided a urine sample which was divided into
      appropriate aliquots for each of urine cytology and NMP 22. Comparative results
      demonstrate a clear superiority of NMP 22 in bladder cancer detection (52.6% vs
      31.6% sensitivity), while specificity was in favor of urine cytology (100% vs
      82.5%). For superficial tumors, sensitivity was 78.5% for NMP 22 and 41.6% for
      cytology and for invasive cancers, sensitivity was 90% for NMP 22 and 60% for
      cytology. Urinary NMP 22 levels were significantly correlated with tumor grade
      and were significantly higher in large tumors than small tumors. NMP 22 test
      results showed sufficient sensitivity in comparison with urine cytology for the
      detection of transitional cell carcinoma. However, we do not think that it is a
      useful tool as a substitute for endoscopic examination for the detection and
      surveillance in bladder cancer.

PMID- 14685797
TI  - Monitoring individual response to brain-tumour chemotherapy: proton MR
      spectroscopy in a patient with recurrent glioma after stereotactic radiotherapy.
AB  - Since antineoplastic activity varies, sensitive methods for individual assessment
      of efficacy are needed. We demonstrate the clinical value of MR spectroscopy in
      monitoring chemotherapy in a patient with recurrent glioma after stereotactic
      radiotherapy. Diagnostic imaging before and after chemotherapy included contrast
      enhanced MRI, single-voxel proton MR spectroscopy ((1)H MRS), (1)H MR
      spectroscopic imaging ((1)H SI), and fluorodeoxyglucose (FDG) positron-emission
      tomography (PET). A significant decrease in choline signal intensity was observed
      2 months after chemotherapy indicating tumour chemosensitivity, in line with
      tumour shrinkage on MRI and decreased uptake of FDG. Assessment of early response
      by MRS may help to improve treatment protocols in other patients.

PMID- 14685798
TI  - Lumbar nerve root avulsion following trauma: balanced fast field-echo MRI.
AB  - Lumbosacral nerve root avulsion uncommonly complicates major trauma. Most
      patients also have pelvic or lumbar fractures. We present a patient who had a
      high-velocity vehicle accident with traumatic hip dislocation without fractures
      of the spine or pelvis. MRI demonstrated lumbosacral traumatic
      pseudomeningoceles. We used balanced fast field echo and MR myelography to make
      the diagnosis and show the extent of the pseudomeningocele.

PMID- 14685799
TI  - Fibrates modify the expression of key factors involved in bile-acid synthesis and
      biliary-lipid secretion in gallstone patients.
AB  - AIMS: Fibrate treatment induces adverse changes in biliary-lipid and bile-acid
      composition. Since the molecular mechanisms underlying these changes are still
      unclear, we have investigated the effect of fibrate treatment on key factors
      involved in bile-acid synthesis, biliary-lipid secretion and cholesterol
      metabolism in gallstone patients. METHODS: Patients with uncomplicated gallstones
      and a serum level of low-density lipoprotein (LDL) cholesterol >130 mg/dl were
      randomly assigned to open-label treatment with bezafibrate, fenofibrate,
      gemfibrozil, or placebo for 8 weeks before elective cholecystectomy. A liver
      specimen was obtained at operation, and the mRNA relative levels for cholesterol
      7alpha-hydroxylase (CYP7A1), hepatocyte nuclear factor-4 (HNF-4), ATP-binding
      cassette transporters MDR3, ABCG5, and ABCG8, human homologue scavenger receptor
      BI, sterol response element binding protein-2 (SREBP-2), 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase and LDL receptor were determined by
      means of reverse-transcriptase polymerase chain reaction. RESULTS: Bezafibrate,
      fenofibrate and gemfibrozil significantly reduced CYP7A1 mRNA levels. The three
      fibrates tested raised the mRNA levels of ABCG5 and SREBP-2, but only bezafibrate
      induced significant changes. Although MDR-3 mRNA levels were slightly increased
      by the three fibrates, no significant differences were obtained. CONCLUSIONS:
      These results show for the first time that fibrate administration to humans
      downregulates CYP7A1. Although ABCG5 and SREBP-2 mRNA levels were slightly
      increased by all treatment groups, only bezafibrate induced significant changes.

PMID- 14685800
TI  - Dropout rates with olanzapine or risperidone: a multi-centre observational study.
AB  - OBJECTIVE: In patients with schizophrenia, risperidone and olanzapine are the two
      most commonly used atypical anti-psychotics. A recent meta-analysis based on
      randomized trials suggests that, in the long term, olanzapine can have a lower
      frequency of treatment discontinuation (or dropout) in comparison with
      risperidone. To better test this hypothesis, our observational study was aimed at
      assessing whether or not this advantage of olanzapine versus risperidone could be
      confirmed in a patient series examined in an observational setting. METHODS: Our
      study was based on a retrospective multi-centre observational design. We
      collected the following information from each patient: demographic
      characteristics; current anti-psychotic treatment (olanzapine or risperidone,
      under the condition of a stable therapy over months -1 to -4); cumulative dose of
      the drug; previous anti-psychotic treatment (during months -5, -6, -7 and/or,
      when available, also before month -7); daily dose and treatment duration. Our
      primary analysis traced back the patient's history from the date of enrollment
      retrospectively up to month -7. The secondary analysis followed-up the patient's
      history prior to month -7, thus extending this retrospective recording as long as
      possible (depending on what information was actually available for individual
      patients). RESULTS: The patients were enrolled from 31 institutions. In our
      primary analysis (months -1 to -7), a total of 144 patients were included; in
      this subgroup treated with olanzapine or risperidone as initial drug ( n=94), we
      observed 4 of 54 switches from olanzapine to risperidone and 11 of 40 switches
      from risperidone to olanzapine ( P=0.01). A total of 454 patients were enrolled
      in our secondary analysis (from month -1 up to month -73); the same comparison
      showed 9 of 236 switches from olanzapine to risperidone and 17 of 150 switches
      from risperidone to olanzapine ( P=0.004). CONCLUSION: Our analysis confirms the
      results of a recent meta-analysis and shows that olanzapine might imply a lower
      risk of dropout than risperidone.

PMID- 14685801
TI  - Congruence on medication between patients and physicians involved in patient
      course.
AB  - OBJECTIVE: To analyse congruence on medication throughout patient courses,
      including an acute admission to a medical department. DESIGN: A prospective,
      observational study. Data were collected from patient records in primary health
      care, hospital departments, from the Health Insurance database and through
      patient interviews. SETTING: Departments of internal medicine, general practice
      and patients' homes. MAIN OUTCOME MEASURES: Number, type and character of
      discrepancies between paired sources of information on patient medication at
      predefined time points throughout the complete patient course. Assessment of
      likelihood and severity of potential untoward effects of discrepancies. RESULTS:
      Data were obtained for 75 of 99 consecutive patients included. Patients stated
      use of four drugs (median, range 0-17) at admission, five (0-16) at discharge and
      four (0-15) 1 month after discharge. At admission, 11 patients used no drugs. A
      median of one (0-20) to three (0-16) discrepancies per patient were identified in
      seven paired source comparisons with no improvement along patient course. Full
      agreement throughout the course was found in six patients (8%; 95% confidence
      interval: 3-17%). No association was found among source discrepancies and number
      of drugs and age. Of discrepancies, 4-13% were considered serious and likely to
      cause untoward effects. Discrepancies due to synonymous and analogous drugs
      accounted for 2-7% of the discrepancies. CONCLUSION: Congruence between sources
      of information on medication throughout patient courses cannot be obtained with
      separate medication charts. Discrepancies among patient, general practitioner and
      hospital give rise to a definitive risk of serious untoward effects.

PMID- 14685802
TI  - Absolute contraindications in relation to potential drug interactions in
      outpatient prescriptions: analysis of the first five million prescriptions in
      1999.
AB  - OBJECTIVES: Adverse drug interactions increase morbidity and mortality. To
      prevent these, situations leading to adverse prescriptions must be clarified.
      This study quantifies and analyses prescriptions with potential adverse drug
      interactions in primary health care in the North of France over a 3-month period.
      METHODS: All prescriptions administered between 1 January 1999 and 31 March 1999
      were analysed to identify potential interactions amongst drugs appearing on the
      same prescription sheet. The regional French healthcare database was compiled to
      further classify contraindications. RESULTS: There were 5,358,374 prescriptions
      administered to 44% of the overall population of the Nord-Pas de Calais area
      (1,754,372 patients per 3,990,167 general population). There were 14,390
      prescriptions classified as either absolute (26%) or relative contraindications
      (74%). Nine drug categories accounted for most of the absolute contraindications:
      dopaminergic antiparkinsonians, neuroleptic agents, migraine treatments (such as
      ergot alkaloids, sumatriptan and other triptan derivatives), prokinetic drugs
      (cisapride), antibacterial drugs (macrolides), antifungals (imidazoles),
      antiarrhythmics, beta-blockers and analgesics (opioids and floctafenine). In 54%
      of patients exposed, the incurred risk was either QT prolongation/Torsade de
      Pointes or antagonism of dopaminergic antiparkinson agents with dopamine receptor
      antagonists prescribed as antipsychotic agents. CONCLUSIONS: Among a non-selected
      population of ambulatory outpatients, the number of quarterly prescriptions with
      contraindications with potentially harmful drug interactions is 27 in 10,000
      prescriptions. This would extrapolate to nearly 200,000 contraindications on same
      prescription sheets in France in the first quarter of 1999.

PMID- 14685803
TI  - Are object- and space-based attentional biases both important to free-viewing
      perceptual asymmetries?
AB  - In contrast to unilateral neglect patients, who overattend to the right
      hemispace, normal participants attend more to the left: a phenomenon known as
      pseudoneglect. Two experiments examined whether pseudoneglect results from object
      or space-based attentional biases. Normal participants ( n=38, 22) made
      luminance judgments for two left/right mirror-reversed luminance gradients
      (greyscales task). The relative lateral position of the greyscales stimuli was
      manipulated so that object- and space-based coordinates were congruent or
      incongruent. A baseline condition was also included. A leftward bias, found for
      the baseline condition, was annulled in the incongruent condition, demonstrating
      an opposition of object- and space-based biases. The leftward bias was reduced in
      the congruent condition where object- and space-based biases were expected to be
      additive. This effect was attributed to extraneous factors, which were avoided in
      the second experiment by presenting the greyscales stimuli sequentially. Once
      again, no bias was observed in the incongruent condition where object- and space
      based biases were opposed. The leftward bias in the congruent condition was the
      same as the baseline. The results can be explained by a combination of space- and
      object-based biases or by space-based biases alone and are discussed with
      reference to a variety of models, which describe the distribution of attention
      across space.

PMID- 14685804
TI  - The relative effects of external spatial and motoric factors on the bimanual
      coordination of discrete movements.
AB  - The ability to coordinate the two hands effectively is a fundamental requirement
      for many everyday tasks. To investigate how bimanual coordination is achieved we
      asked subjects to perform discrete bimanual key-press responses under conditions
      in which the motoric (i.e., muscles employed) and external spatial (i.e.,
      direction of movement in external space) relationships between the actions of the
      left and right index fingers were systematically varied. Subjects made
      simultaneous right and left index finger key-presses in response to an auditory
      tone. The right finger always made downward flexion movements whilst the left
      finger either flexed in a downward/upward direction, or extended in a
      downward/upward direction. Unimanual control trials of each movement type for
      both hands were also performed. Reaction times for each hand (RTs) and the inter
      response interval (IRI) were recorded. Right hand RTs were significantly affected
      only when the left finger performed motorically different actions, but were
      unaffected by the external spatial direction in which the left hand's actions
      were made. The IRI results followed a similar pattern with the worst coordination
      (highest IRI) occurring when the left finger performed different motor actions to
      the right finger regardless of the direction of the left hand movement. In
      contrast to other recent results from experiments examining oscillatory tasks
      (e.g., Mechsner et al. 2001), our results suggest that in discrete tasks there is
      a dominance of the motor relationship between the hands over the external spatial
      relationship.

PMID- 14685805
TI  - Predictability influences finger force control when catching a free-falling
      object.
AB  - We studied grip force control when catching a free-falling object with the
      dominant hand. An instrumented object was dropped either from the subjects'
      opposite hand or expectedly from the experimenter's hand. Following digit-object
      contact, triggered responses were observed in the load and grip force profiles.
      The peak rates of load force increase and the peak load forces produced at the
      time the catching fingers made contact with the object were of similar magnitude
      for the experimenter- and self-release conditions. However, the peak rates of
      grip force development and the peak grip forces were more pronounced when the
      object was dropped by the experimenter. These findings suggest that the
      prediction of the load magnitude was less precise when the object was dropped
      from the experimenter's hand. In addition, a correlation analysis between maximum
      grip and load force rates revealed a less precise coupling between the force
      rates in the experimenter-release condition. The time lags between maximum force
      rates and maximum forces were longer for the experimenter-release than for the
      self-release condition. These observations may indicate a less precise temporal
      coupling between grip and load force profiles in the experimenter-release
      condition. As observed during other manipulative tasks, the co-ordination between
      grip and load forces is a prerequisite to cope with collision forces when
      catching free-falling objects. Grip force control during catching is both highly
      automatic and flexible depending on the predictability of the task.

PMID- 14685806
TI  - Two types of neuron are found within the PPT, a small percentage of which project
      to both the LM-SG and SC.
AB  - The pedunculopontine tegmental nucleus (PPT) projects its cholinergic fibers to
      both the lateralis medialis-suprageniculate nucleus (LM-Sg) and the superior
      colliculus (SC). For the purpose of verification of whether a single neuron in
      the PPT projects to both the LM-Sg and the SC, we injected dextran
      tetramethylrhodamine (DR) into the LM-Sg and dextran fluorescein (DF) into the
      ipsilateral SC. The DR-positive neurons labeled retrogradely in the PPT are small
      (mean: 27.13+/-1.22 micro m) and distributed in the rostral two-thirds of this
      nucleus, whereas the DF-positive neurons are small (mean: 27.54+/-1.16 micro m)
      or medium-sized (mean: 40.18+/-1.43 micro m), and are located throughout the PPT.
      Thirty-five percent of all labeled neurons are double-labeled and small. The
      present study indicates that the PPT projection to the LM-Sg in part involves
      neurons bifurcating to the SC.

PMID- 14685807
TI  - Bioactivity of a peptide derived from acetylcholinesterase in hippocampal
      organotypic cultures.
AB  - While the molecular basis underlying the non-classical actions of
      acetylcholinesterase (AChE) is presently unknown, a candidate peptide sequence
      located at the C-terminus of AChE (AChE-peptide) has recently been identified.
      This study explored the bioactivity of synthetic AChE-peptide using in vitro
      organotypic cultures of rat hippocampus. Neurotrophic effects, detected as
      increased neurite outgrowth from MAP-immunopositive neurones, were apparent using
      1 h exposure to 1-10 nM AChE-peptide. As exposure time increased, cell death
      occurred as indicated by TdT-mediated dUTP biotin nick-end labelling (TUNEL).
      This process was accelerated at higher AChE-peptide concentrations, with lactate
      dehydrogenase (LDH) efflux observed following prolonged exposure to 1-10 microM
      AChE-peptide. Apoptotic cells were detected by Hoechst 33342 staining following
      24 h application of 10 nM AChE-peptide. However, propidium iodide reactivity
      revealed a simultaneous loss of membrane integrity indicative of necrosis,
      suggesting that AChE-peptide induces cell death via a continuum of apoptotic and
      necrotic processes. Prolonged exposure to AChE-peptide also resulted in a
      concentration-dependent reduction in neurite outgrowth from MAP2-positive
      neurons, although immunohistochemical studies provided some evidence of
      differential responsiveness in GABAergic, cholinergic and somatostatin neurones.
      In addition, bioactivity was sequence specific since a scrambled AChE-peptide
      analogue, as well as the corresponding BuChE-peptide, was ineffective. In
      conclusion, the bioactivity associated with the AChE-peptide sequence may account
      for the non-cholinergic actions of AChE, whilst its neurotrophic-apoptotic
      necrotic spectrum of action may be involved in the aetiology of neurodegenerative
      disorders such as Alzheimer's disease.

PMID- 14685808
TI  - Modulation of interhemispheric inhibition during passive movement of the upper
      limb reflects changes in motor cortical excitability.
AB  - We investigated modulation of inhibition of motor evoked potentials in the left
      forearm musculature attributable to changes in corticomotor excitability induced
      by passive rhythmic movement of the right limb. In the first experiment, eight
      healthy volunteers pre-activated their left flexor carpi radialis (FCR) in a
      simple isometric contraction (2.5-7.5% MVC) while their right hand underwent
      passive wrist flexion-extension. Transcranial magnetic (TMS) or electrical (TES)
      stimulation was applied to the right motor cortex and responses recorded from the
      test (left) limb in eight phases of the wrist flexion-extension cycle of the
      passively driven right limb. In half of the trials TMS conditioning was applied
      to the left motor cortex. The conditioning stimulus significantly inhibited TMS
      evoked responses in the test FCR muscle, whereas TES-evoked responses did not
      appear to be inhibited. For TMS-evoked responses only, inhibition in the static
      pre-activated left FCR was modulated such that inhibition was greater when the
      right wrist was passively flexing than when it was extending. In the second
      experiment TMS was applied to the right motor cortex, contralateral to the test
      (left) limb, with the right hand either passively extending or flexing through
      the neutral position. Conditioning was applied to the left motor cortex at a
      range of intensities adjusted to threshold for flexion and extension movements.
      No difference was evident in the maximum magnitude of inhibition between the
      extension and flexion conditions. We propose there is an increased absolute
      threshold for recruitment and a decreased gain of inhibitory callosal pathways
      during extension phases of the wrist flexion-extension cycle.

PMID- 14685809
TI  - Control of fixation and saccades during an anti-saccade task: an investigation in
      humans with chronic lesions of oculomotor cortex.
AB  - Fourteen patients with a chronic, unilateral lesion restricted to the frontal
      lobe (twelve involving the frontal eye field (FEF)), nine patients with a
      chronic, unilateral lesion restricted to posterior association cortex (eight
      involving the intraparietal sulcus (IPS)), and twelve neurologically normal
      control subjects were studied in an anti-saccade task. A combination of
      manipulating cuing and fixation offset enabled us to examine the effects of
      chronic oculomotor lesions on both saccade preparation and voluntary control over
      ocular fixation. Patients with lesions of the FEF made more errors (reflexive
      glances) toward contralesional targets, whereas patients with IPS lesions made
      fewer errors toward contralesional targets. Patients with IPS lesions had
      increased latencies to initiate saccades away from contralesional targets. For
      FEF patients, the presence of a fixation point inhibited the initiation of
      contralesionally directed saccades less than those directed ipsilesionally.
      Saccade preparation in response to a cue did not reduce the inhibitory effect of
      a fixation point on initiating anti-saccades directed either ipsilesionally or
      contralesionally for either patient group. We conclude that chronic IPS lesions
      result in a reduced contralesional visual grasp reflex (VGR) and delayed
      utilization of visual signals in the contralesional field for planning voluntary
      eye movements. In contrast, patients with chronic FEF lesions are impaired in
      inhibiting the VGR toward contralesional signals, and manifest an asymmetry in
      the balance between fixation and saccade activity. Moreover, voluntary control of
      fixation is compromised after chronic damage to either frontal or parietal
      oculomotor cortex.

PMID- 14685810
TI  - Human corticospinal excitability during a precued reaction time paradigm.
AB  - The purpose of this study was to investigate the time-course of corticospinal
      excitability during reaction time (RT), and compare the excitability when a
      precue provided information regarding both the direction and extent of the
      upcoming movement ('Full' condition), specified the direction of the upcoming
      movement only ('Direction' condition), or provided no information at all ('None'
      condition). Ten healthy, right-handed subjects performed a four-choice RT task
      that involved flexion and extension of dominant wrist. Transcranial magnetic
      stimulation (TMS) was presented at random intervals over a period of 120 ms prior
      to the subject's average non-stimulated voluntary electromyography (EMG) activity
      onset. We found that there was a significant relationship between motor-evoked
      potential (MEP) amplitude and TMS onset when both the flexor carpi radialis (FCR)
      and extensor carpi radialis (ECR) acted as an agonist. This relationship could be
      explained using the sigmoidal Boltzmann equation. The slope for the relationship
      did not differ between the Full and Direction conditions, suggesting that
      corticospinal excitability is not altered in the specification of movement
      extent. Both these conditions differed significantly from the None condition. The
      modulation of corticospinal excitability appeared greater in the FCR than in the
      ECR. There was a significant delay in RT the closer in time TMS was presented
      with respect to EMG onset. During extension, there was no difference in slope
      between the three conditions, whereas during flexion the slope was greater in the
      None condition than in the Direction condition, which was in turn greater than in
      the Full condition. This was mirrored in the relationship between agonist MEP
      amplitude and TMS onset for both muscles. It is possible that the gain of the
      corticospinal tract is increased in the conditions in which less information is
      provided in the precue to partly compensate for the increase in RT, which comes
      as a result of the additional processing required in those conditions.

PMID- 14685814
TI  - Multisensory integration in the estimation of relative path length.
AB  - One of the fundamental requirements for successful navigation through an
      environment is the continuous monitoring of distance travelled. To do so, humans
      normally use one or a combination of visual, proprioceptive/efferent, vestibular,
      and temporal cues. In the real world, information from one sensory modality is
      normally congruent with information from other modalities; hence, studying the
      nature of sensory interactions is often difficult. In order to decouple the
      natural covariation between different sensory cues, we used virtual reality
      technology to vary the relation between the information generated from visual
      sources and the information generated from proprioceptive/efferent sources. When
      we manipulated the stimuli such that the visual information was coupled in
      various ways to the proprioceptive/efferent information, human subjects
      predominantly used visual information to estimate the ratio of two traversed path
      lengths. Although proprioceptive/efferent information was not used directly, the
      mere availability of proprioceptive information increased the accuracy of
      relative path length estimation based on visual cues, even though the
      proprioceptive/efferent information was inconsistent with the visual information.
      These results convincingly demonstrated that active movement (locomotion)
      facilitates visual perception of path length travelled.

PMID- 14685816
TI  - Monitoring the air quality around an oil refinery through the use of diffusive
      sampling.
AB  - Diffusive sampling has been used to study the spatial distribution of SO(2),
      NO(2), NO(x), NH(3) and BTX (benzene, toluene and xylenes) near an oil refinery
      located in Falconara, Italy, over the period from March to October 2001. Three
      different categories of sampling sites (roadside, residential and background)
      were studied. In total, 56 sites were monitored. The results were evaluated on
      the basis of the limit values found in the European Directives. The results of
      the defined study indicate that the measured concentrations were substantially
      lower than the ambient air quality standard with the maximum concentrations being
      generally found much closer to emission sources. The monitoring method described
      here can be used to assess integrated concentration levels over long periods of
      time and to identify pollution "hotspots" where concentrations are likely to be
      consistently high. Identification of these hotspots may help to assess air
      quality and to implement proper action plans, especially in locations where
      industrial and urban pollution coexist.

PMID- 14685815
TI  - Analysis of neem oils by LC-MS and degradation kinetics of azadirachtin-A in a
      controlled environment. Characterization of degradation products by HPLC-MS-MS.
AB  - Since it was first isolated, the oil extracted from seeds of neem (Azadirachtin
      indica A juss) has been extensively studied in terms of its efficacy as an
      insecticide. Several industrial formulations are produced as emulsifiable
      solutions containing a stated titer of the active ingredient azadirachtin-A (AZ
      A). The work reported here is the characterization of a formulation of this
      insecticide marketed under the name of Neem-azal T/S and kinetic studies of the
      major active ingredient of this formulation. We initially performed liquid-liquid
      extraction to isolate the neem oil from other ingredients in the commercial
      mixture. This was followed by a purification using flash chromatography and semi
      preparative chromatography, leading to (13)C NMR identification of structures
      such as azadirachtin-A, azadirachtin-B, and azadirachtin-H. The neem extract was
      also characterized by HPLC-MS using two ionization sources, APCI (atmospheric
      pressure chemical ionization) and ESI (electrospray ionization) in positive and
      negative ion modes of detection. This led to the identification of other
      compounds present in the extract-azadirachtin-D, azadirachtin-I, deacetylnimbin,
      deacetylsalannin, nimbin, and salannin. The comparative study of data gathered by
      use of the two ionization sources is discussed and shows that the ESI source
      enables the largest number of structures to be identified. In a second part,
      kinetic changes in the main product (AZ-A) were studied under precise conditions
      of pH (2, 4, 6, and 8), temperature (40 to 70 degrees C), and light (UV, dark
      room and in daylight). This enabled us to determine the degradation kinetics of
      the product (AZ-A) over time. The activation energy of the molecule (75+/-9 kJ
      mol(-1)) was determined by examining thermal stability in the range 40 to 70
      degrees C. The degradation products of this compound were identified by use of
      HPLC-MS and HPLC-MS-MS. The results enabled proposal of a chemical degradation
      reaction route for AZ-A under different conditions of pH and temperature. The
      data show that at room temperature and pH between 4 and 5 the product degrades
      into two preferential forms that are hydrolyzed to a single product over time and
      as a function of pH change.

PMID- 14685817
TI  - Voltammetric study of glibenclamide at carbon paste and Sephadex-modified carbon
      paste electrodes.
AB  - The oxidative behaviour of the antidiabetic agent glibenclamide on a bare carbon
      paste electrode (CPE) and a Sephadex-modified carbon paste electrode (SMCPE) was
      explored by cyclic and differential pulse voltammetry (DPV). The analysis
      procedure consisted of an open circuit accumulation step in stirred sample
      solution of Britton-Robinson buffer (0.04 mol L(-1), pH 2.0). This was followed
      by medium exchange to a clean solution of Britton-Robinson buffer (0.04 mol L(
      1), pH 5.0), and subsequently an anodic potential scan was effected to obtain the
      voltammetric peak. The glibenclamide oxidation peak current obtained by DPV was
      proportional to the concentration of the glibenclamide in the range of 1.0 x 10(
      9) mol L(-1) to 5.0 x 10(-8) mol L(-1) for 180 s accumulation time, with a
      detection limit of 4.0 x 10(-10) mol L(-1). A method was developed for the
      determination of glibenclamide in formulation and spiked human serum. Moreover,
      the proposed procedure was used to estimate the serum concentrations after oral
      administration of a 5 mg tablet of glibenclamide to three diabetic subjects.

PMID- 14685818
TI  - Laboratory skills: mechanics and other hands-on skills.

PMID- 14685819
TI  - Quantitative analyses of cross-sectional shape of the distal radius in three
      species of macaques.
AB  - I conducted quantitative analyses of the cross-sectional shape of the distal
      radial shaft in three species of macaques, which differ in locomotor behavior:
      semi-terrestrial Japanese macaques ( Macaca fuscata), arboreal long tailed
      macaques ( M. fascicularis), and relatively terrestrial rhesus macaques ( M.
      mulatta). I took CT scans of the distal radial shafts of a total of 180 specimens
      at the level of the inferior radio-ulnar articulation. From each CT image, the
      periosteal outline of the radius was traced automatically by a digital imaging
      technique. I determined five points (landmarks) on the outline by developing a
      standardized morphometric technique. Bone surface lengths were measured by using
      these landmarks and their soft tissue correlates were investigated. The results
      of this study were as follows: (1) Semi-terrestrial M. fuscata has features that
      are approximately intermediate between those of the other two species. M. fuscata
      has a relatively small groove for M. abductor pollicis longus and a large groove
      for Mm. extensor carpi radialis longus et brevis. These characters resemble those
      of M. fascicularis. On the other hand, the ulnar notch of M. fuscata is
      relatively large, a character which is similar to that of M. mulatta. Moreover,
      compared to the other two macaques, the surface of the flexor muscles of M.
      fuscata is intermediate in size. (2) The more terrestrial M. mulatta has a
      relatively large groove for M. abductor pollicis longus and a small groove for
      Mm. extensor carpi radialis longus et brevis. Moreover, M. mulatta has a
      relatively large ulnar notch and a small surface for the flexor muscles. (3) The
      arboreal M. fascicularis has similar features to those of M. fuscata for the
      first and second relative size index. However, in the ulnar notch, M.
      fascicularis has a peculiar character and the surface for the flexor muscles is
      relatively large compared to those of the other two species. These results can be
      interpreted in terms of positional habits and presumed functional demands. A form
      functional study by Lemelin and Schmitt also corroborates the interpretations of
      the present study. Thus, the distal region of the forearm strongly reflects
      muscular development and joint resultant force, and is an important region for
      investigating locomotor adaptations in primates. The present study reveals the
      possibility of using this type of morphometric analysis for reconstructing the
      positional behavior of fossil primates.

PMID- 14685820
TI  - Chemical taxonomy of the Xibei tree peony from China by floral pigmentation.
AB  - Petal flavonoid compositions of 39 tree peony cultivars from Xibei (northwest
      China) were investigated in order to study the chemotaxonomic relationship among
      tree peony species. Six anthocyanins, the 3- O-glucosides and 3,5-di- O
      glucosides of three anthocyanidins-pelargonidin (Pg), cyanidin (Cy), and peonidin
      (Pn)-exist in petals without a blotch at the base. The flowers are classified
      into three anthocyanidin phenotypes: 'Pn, Pg>Cy'; 'Pn, Cy'; and 'Pn, Cy>Pg'.
      Furthermore, the yellow pigments are identified as three flavones and three
      flavonols: apigenin, luteolin, chrysoeriol, and kaempferol, quercetin, and
      isorhamnetin, respectively. Ward's minimum-variance cluster analysis with
      principal component analysis produced a dendrogram using standardized scores of
      20 pigment variables. Of 39 cultivars, 11 clustered with white flowered Paeonia
      rockii and 17 with pink flowered P. rockii. The other 11 cultivars matched either
      P. delavayi or P. potaninii. The result suggests that the Xibei tree peony
      originated mainly from P. rockii.

PMID- 14685821
TI  - Anatomically based geometric modelling of the musculo-skeletal system and other
      organs.
AB  - Anatomically based finite element geometries are becoming increasingly popular in
      physiological modelling, owing to the demand for modelling that links organ
      function to spatially distributed properties at the protein, cell and tissue
      level. We present a collection of anatomically based finite element geometries of
      the musculo-skeletal system and other organs suitable for use in continuum
      analysis. These meshes are derived from the widely used Visible Human (VH)
      dataset and constitute a contribution to the world wide International Union of
      Physiological Sciences (IUPS) Physiome Project (www.physiome.org.nz). The method
      of mesh generation and fitting of tricubic Hermite volume meshes to a given
      dataset is illustrated using a least-squares algorithm that is modified with
      smoothing (Sobolev) constraints via the penalty method to account for sparse and
      scattered data. A technique ("host mesh" fitting) based on "free-form"
      deformation (FFD) is used to customise the fitted (generic) geometry. Lung lobes,
      the rectus femoris muscle and the lower limb bones are used as examples to
      illustrate these methods. Geometries of the lower limb, knee joint, forearm and
      neck are also presented. Finally, the issues and limitations of the methods are
      discussed.

PMID- 14685822
TI  - Effects of contact-induced membrane stiffening on platelet adhesion.
AB  - The adhesion of platelets plays an essential role in thrombogenesis. Adhesion
      occurs at sites called focal adhesions (FA), where cell-membrane receptors bind
      specifically to substrate proteins and couple to each other and to the
      cytoskeleton via various cellular proteins. The resulting molecular structure
      suggests that the cortex stiffens at the FA, which likely affects platelet
      adhesion. This hypothesis is explored by structural analysis and parametric
      investigation. The cortex is modeled as a shell anchored to the substrate by
      adhesion forces and subjected to a detachment force. Equilibrium considerations
      result in a non-linear, two-point boundary value problem that is solved
      numerically. The results show that cortex stiffening significantly influences the
      force required for detachment as well as the cell-membrane internal stresses. The
      magnitude of these effects depends on the ratio of adhesion-to-bending energies
      and on the inclination of the detachment force. Because the cortex stiffening
      depends on cellular events, these results suggest a possible mechanism by which
      platelets can control their adhesion and protect themselves from damage.

PMID- 14685823
TI  - Disposition to recognize goals in infant chimpanzees.
AB  - Do nonhuman primates attribute goals to others? Traditional studies with
      chimpanzees provide equivocal evidence for "mind reading" in nonhuman primates.
      Here we adopt looking time, a methodology commonly used with human infants to
      test infant chimpanzees. In this experiment, four infant chimpanzees saw computer
      generated stimuli that mimicked a goal-directed behavior. The baby chimps
      performed as well as human infants, namely, they were sensitive to the
      trajectories of the objects, thus suggesting that chimpanzees may be endowed with
      a disposition to understand goal-directed behaviors. The theoretical implications
      of these results are discussed.

PMID- 14685824
TI  - Association between polymorphism of the dopamine transporter gene and early
      smoking onset: an interaction risk on nicotine dependence.
AB  - Previous studies suggested that a polymorphism in the dopamine transporter gene
      (SLC6A3) is associated with nicotine dependence and age of smoking onset, but the
      conclusion was controversial. To detect the association of a G-->A polymorphism
      (NCBI dbSNP cluster ID: rs27072) in 3'-untranslated region of the SLC6A3 with
      nicotine dependence and early smoking onset, we recruited 253 sibships including
      668 nicotine-dependent siblings from a rural district of China. The sibship
      disequilibrium tests (SDT) showed that the rs27072-A allele is significantly
      associated with smoking onset < or =18 years (kappa2=9.78, p=0.003 in severely
      nicotine-dependent smokers, and kappa2=4.24, p=0.058 in total smokers), but not
      significantly associated with severe nicotine dependence. Conditional logistic
      regression showed that the risk of early smoking onset by the rs27072-A allele
      was almost three times greater in severely nicotine-dependent smokers [Odds ratio
      (OR)=11.3, 95% confidence interval (CI)=1.5-85.6] than that in total smokers.
      Linear regression showed that rs27072-A allele also increased the risk of
      nicotine dependence by early smoking onset compared with homozygous rs27072-G
      genotype. Although these findings are preliminary and need validation, the
      results suggest that a polymorphism in the SLC6A3 may play important roles in
      smoking onset, and there may be an interactive effect between the SLC6A3 and
      early smoking onset on modulating the susceptibility of nicotine dependence.

PMID- 14685825
TI  - Common single nucleotide polymorphisms of the MDR1 gene have no influence on its
      mRNA expression level of normal kidney cortex and renal cell carcinoma in
      Japanese nephrectomized patients.
AB  - In this study, we have quantified the mRNA expression levels of multidrug
      resistance gene 1 (MDR1) in the normal kidney cortex and renal cell carcinoma
      (RCC) segments from 24 Japanese nephrectomized patients by real-time polymerase
      chain reaction (PCR). The mRNA expression level of MDR1 in RCC segments was
      significantly decreased in comparison with each normal segment (P=0.0042, by
      Student's paired t-test). In addition, the ten common single nucleotide
      polymorphisms (SNPs) of the MDR1 gene in the patients were assessed using the PCR
      restriction enzyme fragment length polymorphism method to investigate the
      influence of these SNPs on its mRNA expression levels. The allele frequencies of
      these SNPs were comparable with our previous report in the Japanese recipients of
      living-donor liver transplantation (Goto et al., Pharmacogenetics 12:451-457;
      2002). MDR1 expression levels in the normal kidney cortex were independent on the
      five SNPs, which were polymorphic in the Japanese population. Furthermore, the
      effect of the SNPs on expression levels of MDR1 mRNA in RCC segments was not
      recognized. These findings suggest that the common SNPs in the MDR1 gene have no
      influence on the expression of its transcript in RCC segments as well as in the
      normal kidney cortex.

PMID- 14685826
TI  - Structural and immunocytochemical studies on alpha-N-acetylgalactosaminidase
      deficiency (Schindler/Kanzaki disease).
AB  - Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki
      disease) is a clinically and pathologically heterogeneous genetic disease with a
      wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease)
      and late onset angiokeratoma corporis diffusum (Kanzaki disease). In alpha-NAGA
      deficiency, there are discrepancies between the genotype and phenotype, and also
      between urinary excretion products (sialyl glycoconjugates) and a theoretical
      accumulated material (Tn-antigen; Gal NAcalpha1-O-Ser/Thr) resulting from a
      defect in alpha-NAGA. As for the former issue, previously reported genetic,
      biochemical and pathological data raise the question whether or not E325K
      mutation found in Schindler disease patients really leads to the severe phenotype
      of alpha-NAGA deficiency. The latter issue leads to the question of whether alpha
      NAGA deficiency is associated with the basic pathogenesis of this disease. To
      clarify the pathogenesis of this disease, we performed structural and
      immunocytochemical studies. The structure of human alpha-NAGA deduced on homology
      modeling is composed of two domains, domain I, including the active site, and
      domain II. R329W/Q, identified in patients with Kanzaki disease have been deduced
      to cause drastic changes at the interface between domains I and II. The
      structural change caused by E325K found in patients with Schindler disease is
      localized on the N-terminal side of the tenth beta-strand in domain II and is
      smaller than those caused by R329W/Q. Immunocytochemical analysis revealed that
      the main lysosomal accumulated material in cultured fibroblasts from patients
      with Kanzaki disease is Tn-antigen. These data suggest that a prototype of alpha
      NAGA deficiency in Kanzaki disease and factors other than the defect of alpha
      NAGA may contribute to severe neurological disorders, and Kanzaki disease is
      thought to be caused by a single enzyme deficiency.

PMID- 14685827
TI  - Review of the management of recurrent inguinal hernia.
AB  - BACKGROUND: There is little available evidence on the optimal management of
      recurrent inguinal hernia, particularly if the original procedure involved the
      use of mesh. This study was a review of recurrent hernia repair in a district
      hospital, involving both laparoscopic and open procedures. METHODS: The case
      notes of all patients who had a repair of a recurrent hernia between 1991 and
      2000, inclusive, were examined; 171 procedures were included. Where known, the
      original repair was a nylon darn in 31%, mesh repair in 18%, and laparoscopic
      repair in 8%. RESULTS: The recurrent hernia was repaired using a Lichtenstein
      open mesh technique in 63% and by the totally extraperitoneal (TEP) method in
      22%. Complication rates were highest after emergency surgery (all had open
      surgery), where 71% had complications and one patient died. For elective repairs,
      complication rates were similar after open (13%) and TEP (8%) repairs. The
      duration of hospital stay was also similar (1.2 vs 1.3 days, respectively), and a
      single recurrence was seen in each group. Patients with recurrence after primary
      mesh repair were also managed by both techniques with similar results. Open re
      operation for mesh failure was technically straightforward. CONCLUSIONS: Most
      recurrent hernias are still repaired by open techniques. There was no convincing
      evidence of different outcomes for open and TEP repairs in this review. Even when
      the original hernia repair involved the use of mesh, further open repair by an
      experienced surgeon is justified.

PMID- 14685828
TI  - NMR investigation of the heme electronic structure in deoxymyoglobin possessing a
      fluorinated heme.
AB  - The heme electronic structures of deoxymyoglobins (deoxy-Mbs) reconstituted with
      13,17-bis(2-carboxylatoethyl)-3,8-diethyl-2,12,18-trimethyl-7
      (trifluoromethyl)porphyrinatoiron(III) (7-PF), 13,17-bis(2-carboxylatoethyl)-3,7
      difluoro-2,8,12,18-tetramethylporphyrinatoiron(III) (3,7-DF), and 13,17-bis(2
      carboxylatoethyl)-3,8-diethyl-2-fluoro-7,12,18-trimethylporphyrinatoiron(III) (2
      MF) have been characterized by (1)H and (19)F NMR. The analysis of heme methyl
      proton shift patterns of the hemes in their bis-cyano forms demonstrated that,
      owing to the substitution of a strongly electron-withdrawing perfluoromethyl
      group, CF(3), to porphyrin, the porphyrin pi-system of 7-PF is more significantly
      distorted from four-fold symmetry than those of the ring-fluorinated hemes, 3,7
      DF and 2-MF. The presence of the heme orientation disorder resulted in the
      observation of the two well-resolved (19)F signals in the spectra of deoxy-Mbs
      possessing 7-PF and 2-MF. The (19)F signals of deoxy-Mb possessing 7-PF exhibited
      a relatively large difference in paramagnetic shift (approximately 30 ppm),
      despite their small paramagnetic shifts (approximately 30 ppm), supporting the
      significant contribution of a pi spin delocalization mechanism in this Mb due to
      the d-electron configuration derived from the (5)E ground state. On the other
      hand, (19)F signals of deoxy-Mbs with 3,7-DF as well as 2-MF exhibited large
      paramagnetic shifts (approximately 250 ppm) with a relatively small difference in
      the paramagnetic shift (approximately 20 ppm), indicating the predominant
      contribution of spin delocalization, due to a d-electron configuration derived
      from the (5)B(2) ground state. These results demonstrate for the first time that
      the relative contributions of the orbital ground states derived from (5)E and
      (5)B(2) states to the heme electronic structure in deoxy-Mb are affected by the
      distortion of the porphyrin pi-system exerted by chemical properties of the heme
      peripheral side-chains.

PMID- 14685829
TI  - Biomechanical analysis of anterior cervical spine plate fixation systems with
      unicortical and bicortical screw purchase.
AB  - Anterior plate fixation with unicortical screw purchase does not involve the risk
      of posterior cortex penetration and possible injuries of the spinal cord.
      However, there are very few biomechanical data about the immediate stability of
      non-locking plate fixation with unicortical or bicortical screw placement. The
      aim of the present study was to evaluate the immediate biomechanical properties
      in terms of flexibility of a non-locking anterior plate system with 4.5-mm screw
      fixation and unicortical or bicortical screw purchase applied to a single
      destabilized cervical spine motion segment. Using fresh cadaveric cervical spine
      specimens C3-C7, multidirectional flexibility was measured at the level C4-C5
      before and after destabilization and fixation with an anterior plate with either
      unicortical or bicortical screw purchase. The results showed that fixed cervical
      spine segments with anterior plate and bicortical screw purchase were more rigid
      than intact specimens in all modes of testing. The difference was statistically
      significant for flexion and extension ( P<0.001). Plate fixation with unicortical
      screw purchase had statistically significant decreased ranges of motion compared
      to the intact specimen only in extension. Neither unicortical nor bicortical
      screw purchase decreased the range of motion significantly in axial rotation
      compared to the intact specimens. This in vitro study documented that neither
      unicortical nor bicortical screw purchase with non-locking plate fixation can
      increase stability in all modes of testing, in axial rotation in particular.
      Direct comparison between the group with uni- and that with bicortical screw
      fixation did not reveal significant differences, and therefore no advantage was
      shown for either type of screw fixation. Therefore, we demonstrated that both uni
      and bicortical screw purchase with non-locking plate fixation can decrease
      immediate flexibility of the tested motion segment, with better results for
      bicortical purchase. No significant differences were found comparing the two
      groups of screw fixation. These data suggest that unicortical screw fixation can
      be used for anterior plate fixation with a comparable immediate stability to
      bicortical screw fixation.

PMID- 14685830
TI  - A prospective randomized multi-center study for the treatment of lumbar spinal
      stenosis with the X STOP interspinous implant: 1-year results.
AB  - Patients suffering from neurogenic intermittent claudication secondary to lumbar
      spinal stenosis have historically been limited to a choice between a
      decompressive laminectomy with or without fusion or a regimen of non-operative
      therapies. The X STOP Interspinous Process Distraction System (St. Francis
      Medical Technologies, Concord, Calif.), a new interspinous implant for patients
      whose symptoms are exacerbated in extension and relieved in flexion, has been
      available in Europe since June 2002. This study reports the results from a
      prospective, randomized trial of the X STOP conducted at nine centers in the U.S.
      Two hundred patients were enrolled in the study and 191 were treated; 100
      received the X STOP and 91 received non-operative therapy (NON OP) as a control.
      The Zurich Claudication Questionnaire (ZCQ) was the primary outcomes measurement.
      Validated for lumbar spinal stenosis patients, the ZCQ measures physical
      function, symptom severity, and patient satisfaction. Patients completed the ZCQ
      upon enrollment and at follow-up periods of 6 weeks, 6 months, and 1 year. Using
      the ZCQ criteria, at 6 weeks the success rate was 52% for X STOP patients and 10%
      for NON OP patients. At 6 months, the success rates were 52 and 9%, respectively,
      and at 1 year, 59 and 12%. The results of this prospective study indicate that
      the X STOP offers a significant improvement over non-operative therapies at 1
      year with a success rate comparable to published reports for decompressive
      laminectomy, but with considerably lower morbidity.

PMID- 14685831
TI  - One-stage anterior interbody autografting and instrumentation in primary surgical
      management of thoracolumbar spinal tuberculosis.
AB  - There are few articles in the literature concerning anterior instrumentation in
      the surgical management of spinal tuberculosis in the exudative stage. So we
      report here 23 cases of active thoracolumbar spinal tuberculosis treated by one
      stage anterior interbody autografting and instrumentation to verify the
      importance of early reconstruction of spinal stability and to evaluate the
      results of one-stage interbody autografting and anterior instrumentation in the
      surgical management of the exudative stage of throracolumbar spinal tuberculosis.
      Twenty-three patients, including two children (9 and 15 years old, respectively)
      and 21 adults with thoracolumbar spinal tuberculosis were treated surgically. T9
      to L4 spinal segments were affected, and MRI/CT showed evident collapse of the
      vertebrae because of tuberculous destruction and paravertebral abscess.
      Neurological deficits were found in 15 patients. Before surgery, patients
      received standard anti-tuberculosis chemotherapy for 2 to 3 weeks. Under general
      endotracheal anaesthesia, the patients were placed in right recumbent positions,
      and a transthoracic, lateral extracavitary or extrapleural approach was chosen
      according to the tuberculosis lesion segment. After exposure, the tuberculous
      lesion region, including the collapsed vertebrae and in-between intervertebral
      disc, was almost completely resected in order to release the segmental spinal
      cord. Then, autologous iliac, rib or fibular graft was harvested to complete
      interbody fusion, and an anterior titanium-alloy plate-screw system was used to
      reconstruct the stability of the affected segments. Anti-tuberculosis
      chemotherapy was continued for at least 9 months, and the patients were supported
      with thoracolumbosacral orthosis for 6 months after surgery. All patients were
      followed up for an average of 2 years. All 23 cases were healed without chronic
      sinus formation or any recurrence of tuberculosis during the follow-up period.
      Spinal fusion occurred at a mean of 3.8 months after surgery. Of all patients
      with neurological deficits, 14 patients showed obvious improvement; only one
      patient with Frankel C lesion remained unchanged, but none of the patients got
      worse. During the follow-up period, a mean of 18 degrees of kyphosis correction
      was achieved after surgery in the adult group. Moderate progressive kyphosis
      because of this procedure fusion occurred postoperatively in a 9-year-old child
      after 2 1/2 years; another 15-year-old child did not demonstrate this phenomenon.
      Except for the early loosening of one screw in two cases (which did not affect
      the reconstruction of spinal stability), no other complications associated with
      this procedure were found during follow-up. Early reconstruction of spinal
      stability plays an important role in the surgical management of spinal
      tuberculosis. One-stage anterior interbody autografting and instrumentation in
      the surgical management of the exudative stage of spinal tuberculosis show more
      advantages in selected patients, but supplementary posterior fusion should be
      considered to prevent postoperative kyphosis when this procedure is performed in
      children.

PMID- 14685832
TI  - Improvement by soil yeasts of arbuscular mycorrhizal symbiosis of soybean
      (Glycine max) colonized by Glomus mosseae.
AB  - The effects of the soil yeasts Rhodotorula mucilaginosa, Cryptococcus laurentii
      and Saccharomyces kunashirensis on the arbuscular mycorrhizal (AM) fungus Glomus
      mosseae (BEG 12) was studied in vitro and in greenhouse trials. The presence of
      yeasts or their soluble and volatile exudates stimulated the percentage spore
      germination and hyphal growth of G. mosseae. Percentage root length colonized by
      G. mosseae and plant dry matter of soybean (Glycine maxL. Merill) were increased
      only when the soil yeasts were inoculated prior to the AM fungus. Higher
      beneficial effects on AM colonization and plant dry matter were found when the
      soil yeasts were inoculated as an aqueous solution rather than as a thin agar
      slice. Although soluble and volatile exudates of yeasts benefited the AM
      symbiosis, their modes of action were different.

PMID- 14685833
TI  - Existential concerns of terminally ill cancer patients receiving specialized
      palliative care in Japan.
AB  - BACKGROUND: Although alleviation of existential distress is important for
      terminally ill cancer patients, the concept of existential distress has not been
      fully understood. The aim of this study was to categorize existential concerns of
      Japanese terminally ill cancer patients and explore care strategies based on the
      categorizations. METHODS: A multicenter cross-sectional study in 88 terminally
      ill cancer patients receiving specialized inpatient palliative care was
      performed. The nurses explored patient existential concerns by asking several key
      questions, and recorded the answers that they considered typically described the
      patients' concerns. All statements recorded by the nurses were analyzed using
      content analysis methods. RESULTS: A total of 89 statements were subjected to
      analysis. The categories and their prevalence were: relationship-related concerns
      (22%; isolation, concerns about family preparation, conflicts in relationship),
      loss of control (16%; physical control, cognitive control, control over future),
      burden on others (4.5%), loss of continuity (10%; loss of role, loss of enjoyable
      activity, loss of being oneself), uncompleted life task (6.8%), hope/hopelessness
      (17%), and acceptance/preparation (25%). CONCLUSIONS: Existential concerns of
      Japanese terminally ill cancer patients were categorized as relationship-related
      concerns, loss of control, burden on others, loss of continuity, uncompleted life
      task, hope/hopelessness, and acceptance/preparation. These themes seemed to
      encompass universal human suffering beyond cultural differences, and this
      conceptualization may contribute to the development of effective therapeutic
      interventions to alleviate existential distress.

PMID- 14685834
TI  - Principles of medical ethics in supportive care: a reflection.
AB  - The possibility of medical-moral controversy in contemporary health care delivery
      is occasioned by the interfacing of expanding technology with both professional
      and personal value systems, frequent and significant knowledge deficits on the
      part of health care consumers, and increased circumspection of and economic
      constraints experienced by health care providers. Particularly in an era of
      increasing regulatory mandates and the frequent and lamentable decrease in the
      availability of human, natural, and institutional resources, an understanding of
      the function of ethical analysis is indigenous to care, which is simultaneously
      medically appropriate and morally indicated. But while a familiarity with and an
      appreciation of the potential contribution of ethical reasoning is essential in
      all health care delivery, it assumes critical importance in supportive care. In
      that venue, where the rigors and demands of aggressively therapeutic
      interventions have ceased and the goal and the demeanor of care have shifted to
      the palliative mode, heightened attention to the principles of medical ethics is
      necessary for the balancing of rights and responsibilities for health care
      consumers and providers alike. This issue ultimately can be singularly salient in
      providing care that is patient centered and directed. Individuals acting as moral
      agents, suggesting what "ought" to be done in a given situation, either for
      themselves or as they are involved in rendering or supporting decisions proffered
      for or by other moral agents, particularly those in extremis, those in the throes
      of terminal illness following the collapse of the curative mode, need recourse to
      principles to facilitate their reasoning. Although the employment of each
      principle of medical ethics offers guidelines for reflection on the most
      comprehensive and appropriate care, it is attention to autonomy, informed
      consent, and beneficence that promotes the most effective supportive care. For
      even as the question of medical viability is settled in favor of palliation over
      aggression, there remain the entanglements of psychological stability,
      conflicting value systems, and the impact of the social milieu as well as the
      issues of economic responsibility and resource accountability. It is in the
      attention to the medical ethical principles of autonomy and informed consent,
      especially as amplified by the creation of and respect for advance directives,
      that the most holistic and productive supportive care can be offered. It is also
      in this posture that appeal to the principle of beneficence is made. Just as the
      progress of disease and, therefore, the realistic goals of care change, so too
      can an individual's considered opinion with regard to end-of-life decisions.
      Preserving the integrity of patients and caregivers alike and engaging in
      fruitful and informative dialog prior to seeking volitional authorization or
      operationalizing a supportive approach demonstrates renewed concern for both
      patient autonomy and professional accountability in the provision of a
      comprehensive end-of-life care plan. Discussions will not be avoided until they
      can no longer effectively take place, salient questions will not go unanswered,
      and decisions around end-of-life questions, in the mode of supportive care, will
      not be absent where care was exercised to engage patients in significant dialog
      earlier rather than later in their disease processes.

PMID- 14685836
TI  - Blood pressure nomograms for school children in Iran.
AB  - Currently there are no blood pressure (BP) nomograms based on local data
      available in Iran. In order to obtain data on BP distribution in Iranian school
      children, 8848 children aged 7-12 years were studied in Tehran. BP was found to
      increase with age. Both systolic and diastolic BP showed a positive correlation
      with height and weight in both sexes. The systolic and diastolic BP in boys and
      girls were not significantly different. As the sample was representative of
      Iranian school children, reference standard curves were constructed by modeling
      data using fractional polynomial. The 50th and 95th percentiles of systolic and
      diastolic BP of Iranian children were compared for each age with the results
      reported in the study of the Second Task Force. These percentiles were different
      from the Second Task Force study. Environmental and genetic determinants are
      likely to be responsible for the differences. The differences show that the use
      of local BP nomograms is necessary for assessing the BP levels in Iranian
      children.

PMID- 14685835
TI  - Next of kin's experience of powerlessness and helplessness in palliative home
      care.
AB  - GOALS OF WORK: Powerlessness and helplessness have been very little studied. The
      aims of this study were (1) to describe what characterise such experiences and
      the meaning of them to next of kin of cancer patients in advanced palliative home
      care and (2) to make quantifications. PATIENTS AND METHODS: The study design was
      cross-sectional and targeted next of kin during ongoing palliative home care and
      next of kin of patients who had died 3-9 months earlier; 233 next of kin
      responded (response rate 72%) to a postal questionnaire with both Likert-type and
      open-ended questions. The text responses were analysed with a combined
      qualitative and quantitative content analysis. MAIN RESULTS: Thirty-six percent
      of respondents stated that they had experienced powerlessness and/or helplessness
      every day or several times per week, whereas 33% had never had this experience
      during the palliative home care period. Powerlessness and helplessness concerned
      next of kin's perception of the patient's suffering, of the patient's fading away
      and the next of kin's own feelings of insufficiency and resulted in both physical
      and psychological symptoms, such as muscle tension, headache, loss of appetite,
      anxiety and depression. In addition, powerlessness and helplessness concerned
      also a deeper meaning with existential and social aspects, such as feelings of
      guilt, anger and loneliness. CONCLUSIONS: The main findings provide tools for the
      practitioner to identify situations contributing to next of kin's sense of
      powerlessness and helplessness. The findings are discussed in relation to the
      concepts of symptom control, communication of awareness and humans' search for
      action.

PMID- 14685838
TI  - Risk factors for renal failure in children with non-glomerular nephropathies.
AB  - The aim of the present study was to analyze the progression of chronic renal
      failure (CRF), the effects of modification of risk factors for disease
      progression, and to formulate a theoretical model of CRF progression in an
      unselected group of children with CRF. The study was a cross-sectional,
      retrospective analysis of 92 patients aged 9.2+/-5.8 years with CRF and low-level
      proteinuria [glomerular filtration rate (GFR) 43+/-18 ml/min per 1.73 m(2),
      proteinuria 0.57 g/day, range 0-3.9 g/day]. Inclusion criteria were an
      established diagnosis of CRF and completion of any surgical treatment. The
      etiology of CRF in the majority of patients was congenital uropathy. Sixty-nine
      patients observed for longer than 3 years were divided into two groups according
      to progression of CRF or improvement of GFR. Forty-three patients were on
      renoprotective therapy. Over a 3-year period GFR decreased in 39 children and
      improved in 30 children. There were no differences between the groups in the
      etiology of CRF. Patients with progression of CRF were older ( P<0.08), grew
      faster ( P<0.004), had higher blood pressure ( P<0.01), and were more often
      proteinuric ( P<0.03). Arterial hypertension in patients with progression of CRF
      was resistant to therapy and these patients needed more intensive treatment.
      Renoprotective therapy led to improvement of kidney function in 50% of patients,
      and resistance to renoprotective therapy was correlated with increased body mass
      and height. Patients who received renoprotective drugs showed stabilized kidney
      function ( P<0.007) and decreased proteinuria ( P<0.05) and blood pressure (
      P<0.02), despite higher basal values. In patients on renoprotective therapy in
      whom CRF progressed despite treatment, proteinuria was persistent in contrast to
      patients with improvement ( P<0.02). The best model of CRF progression in the
      path diagram included systolic blood pressure and anthropometric parameters. In
      conclusion, in unselected patients with CRF of non-glomerular origin and nil-to
      moderate proteinuria the main risk factors for CRF progression are rapid somatic
      growth, age, and blood pressure. Arterial hypertension and proteinuria, even of
      mild intensity, differ significantly between patients with progression of CRF and
      those with stable or improved renal function. Renoprotective therapy is related
      to significant slowing of CRF progression, but the risk factors for resistance to
      therapy include persistent proteinuria and somatic growth.

PMID- 14685837
TI  - Resistive index in febrile urinary tract infections: predictive value of renal
      outcome.
AB  - In the absence of specific symptomatology in children, the early diagnosis of
      acute pyelonephritis is a challenge, particularly during infancy. In an attempt
      to differentiate acute pyelonephritis from lower urinary tract infection (UTI),
      we measured intrarenal resistive index (RI). We evaluated its ability to predict
      renal involvement as assessed by dimercaptosuccinic acid (DMSA) scintigraphy. In
      total 157 patients admitted to the pediatric department of the Sisli Etfal
      Hospital with clinical signs of febrile UTI were included in the study. The
      children were divided into groups according to their age at the time of
      ultrasonography (US). RI was measured from the renal arteries with Doppler US in
      the first 72 h in all 157 children. Renal involvement was assessed by (99m)Tc
      DMSA scintigraphy in the first 7 days after admission. The examination was
      repeated at least 6 months later if the first result was abnormal. All available
      patients with an abnormal scintigraphy underwent voiding cystourethrography 4-6
      weeks after the acute infection. All patients with vesicoureteral reflux and
      scarred kidneys were excluded from the study. DMSA scintigraphy demonstrated
      abnormal changes in 114 of 157 children and was normal in the remaining 43
      children. Of these 114 children, 104 underwent repeat scintigraphy, of whom 77
      showed partially or totally reversible lesion(s). Of these 77 children, 17
      children (22%) with vesicoureteral reflux were excluded. Thus, we compared the 43
      children with lower UTI with the 60 children with definite acute pyelonephritis
      at admission. Kidneys with changes of acute pyelonephritis had a mean RI of
      0.744+/-0.06 in infants, 0.745+/-0.03 in preschool children, and 0.733+/-0.09 in
      patients of school age with upper UTI. However, the mean RI was 0.703+/-0.06 in
      infants, 0.696+/-0.1 in preschool children, and 0.671+/-0.09 in school-aged
      patients with lower UTI. The mean RI values were significantly higher in patients
      with upper UTI ( P<0.001). There was a highly significant correlation between RI
      values and the severity of the renal lesion as ranked by DMSA scintigraphy (
      P<0.001). When the cut-off RI value was 0.715, there was an 80% sensitivity and a
      89% specificity for diagnosing upper UTI. Refluxing kidneys and scarred kidneys
      also had higher RI values. In conclusion, RI values were increased significantly
      in children with febrile UTI when renal parenchymal involvement (assessed by DMSA
      scintigraphy) was present. Our results also support the view that the children
      with high RI values are at a high risk of reflux, scarring, or both, which was
      frequently observed in febrile UTI. This might allow identification of patients
      at risk for severe renal lesions that require more aggressive therapy,
      investigation, and follow-up than those with lower UTI.

PMID- 14685839
TI  - Impaired vascular endothelium-dependent relaxation in Henoch-Schonlein purpura.
AB  - Few reports have focused on vascular endothelial function in children with Henoch
      Schonlein purpura (HSP). The purpose of the present study was to assess
      endothelial function and to follow serial changes from the acute to convalescent
      phases in children with HSP. Forearm flow-mediated vasodilation was evaluated in
      21 patients with HSP, aged 4.0-10.3 years (median 6.2 years), and in 14 control
      subjects. Vascular dimension, mean velocity, and flow volume were measured by
      ultrasonography in brachial artery before and after hyperemia, and during
      incremental infusions of nitroglycerin (0.5, 1.0 microg/kg per min). In the
      controls, significant increases in dimension, mean velocity, and flow volume were
      observed in reactive hyperemia ( P<0.01). In contrast, patients in the acute
      phase of HSP showed a flow velocity profile indicating a highly resistant forearm
      circulation, and significantly attenuated responses after hyperemia ( P<0.01 vs.
      control), whereas the responses to nitroglycerin were well preserved. In
      addition, the impaired hyperemic responses recovered in the convalescent phase,
      with no significant differences compared with controls. These results clearly
      suggest that forearm vascular endothelium-dependent relaxation was attenuated in
      patients with acute HSP.

PMID- 14685840
TI  - Renal replacement therapy for acute renal failure in children: European
      guidelines.
AB  - Acute renal failure (ARF) is uncommon in childhood and there is little consensus
      on the appropriate treatment modality when renal replacement therapy is required.
      Members of the European Pediatric Peritoneal Dialysis Working Group have produced
      the following guidelines in collaboration with nursing staff. Good practice
      requires early discussion of patients with ARF with pediatric nephrology staff
      and transfer for investigation and management in those with rapidly deteriorating
      renal function. Patients with ARF as part of multi-organ failure will be cared
      for in pediatric intensive care units where there should be access to pediatric
      nephrology support and advice. The choice of dialysis therapy will therefore
      depend upon the clinical circumstances, location of the patient, and expertise
      available. Peritoneal dialysis has generally been the preferred therapy for
      isolated failure of the kidney and is universally available. Intermittent
      hemodialysis is frequently used in renal units where nursing expertise is
      available and hemofiltration is increasingly employed in the intensive care
      situation. Practical guidelines for and the complications of each therapy are
      discussed.

PMID- 14685841
TI  - Troponin I levels in a hemolytic uremic syndrome patient with severe cardiac
      failure.
AB  - Troponins are highly sensitive and specific biochemical markers of myocardial
      injury that are released into the circulation during myocardial ischemia. We
      describe changes in cardiac troponin I (cTnI) prior to and following clinical
      evidence of severe myocardial dysfunction in a child with hemolytic uremic
      syndrome (HUS). A previously healthy, 22-month-old girl presented with typical
      HUS and stool cultures positive for Escherichia coli O157:H7. She required
      dialysis, blood and platelet transfusions, and insulin for HUS-related diabetes
      mellitus. On the 6th hospital day she had sudden circulatory collapse with a
      blood pressure of 70/40 mmHg and an oxygen saturation of 88%. She responded
      rapidly to emergency resuscitation but had diminished left ventricular function
      (ejection fraction 18%). Four days after the acute event an echocardiogram showed
      normal ventricular size and contractility. She underwent hemodialysis for 22
      days, and renal function was normal after 33 days. cTnI levels were measured with
      a microparticle enzyme immunoassay. cTnI was normal (>0.4 microg/l) 32 h prior to
      cardiac collapse, mildly increased (2.1 microg/l) 8 h before the cardiac
      collapse, severely elevated shortly after the cardiac event (43.1 microg/l), and
      peaked (140.6 microg/l) at 24 h. It then fell gradually and was normal at
      discharge. These results suggest that measurement of cTnI may be a useful
      predictor of cardiac involvement in severely affected children with HUS.

PMID- 14685842
TI  - Re-establishment of the ERA-EDTA Registry.
AB  - The European Dialysis and Transplant Association (EDTA) Registry was established
      in the mid 1960s and its annual reports for many years provided important
      information on the treatment of children in Europe with renal diseases. The last
      report of the former European Renal Association (ERA)-EDTA Registry, based in
      London, was in 1996. Unfortunately, shortly thereafter, for a number of reasons
      the Registry collapsed. However, in June 2000 the ERA-EDTA Registry was re
      established in Amsterdam, The Netherlands, and the first report of this new
      European Registry on renal replacement therapy is now published. Effective
      collaboration of single national registries with the new ERA Registry is
      important for the future development of new successful treatment strategies in
      pediatric renal medicine.

PMID- 14685843
TI  - Renal replacement therapy in children: data from 12 registries in Europe.
AB  - In June 2000 the ERA-EDTA Registry office moved to Amsterdam and started
      collecting core data on renal replacement therapy (RRT) entirely through national
      and regional registries. This paper reports the pediatric data from 12
      registries. The analysis comprised 3,184 patients aged less than 20 years and
      starting RRT between 1980 and the end of 2000. The incidence of RRT rose from 7.1
      per million of age-related population (pmarp) in the 1980-1984 cohort to 9.9
      pmarp in the 1985-1989 cohort, and remained stable thereafter. The prevalence
      increased from 22.9 pmarp in 1980 to 62.1 in 2000. Hemodialysis was the commonest
      form of treatment at the start of dialysis, but peritoneal dialysis gained
      popularity during the late 1980s. Pre-emptive transplantation accounted for 18%
      of the first treatment modality in the 1995-2000 cohort. The relative risk of
      death of patients starting dialysis in the period 1995-2000 was reduced by 36%
      [adjusted hazard ratio (AHR) 0.64 [95% confidence interval (CI) 0.41-1.00] and
      that of those receiving a first allograft by 42% [AHR 0.58 (95% CI 0.34-1.00)],
      compared with patients in the period 1980-1984. The prevalence of RRT in children
      has continued to rise, while its incidence has been stable for about 15 years.
      Patient survival has improved in both dialysis patients and transplant
      recipients. The development of this pediatric registry will form the basis for
      more-detailed and focused studies in the future.

PMID- 14685844
TI  - Acute perirenal extravasation of urine in an infant with non-refluxing
      megaureter.
AB  - Perirenal extravasation of urine is a rare event in congenital uropathies, mostly
      observed perinatally in the case of infravesical obstruction. We describe a male
      infant with a primary non-refluxing obstructive left megaureter who developed an
      acute perirenal extravasation and ascites at the age of 4 weeks. After temporary
      upper urinary diversion, ureterocystoneostomy was successfully performed.
      Intraoperatively, the distal ureter showed an extremely narrow lumen over a
      distance of 3 cm. In the current literature, postnatal management of primary
      megaureters is preferably conservative. Our patient demonstrates an extremely
      rare complication demanding early surgical intervention.

PMID- 14685845
TI  - Seed dispersal by the Florida box turtle (Terrapene carolina bauri) in pine
      rockland forests of the lower Florida Keys, United States.
AB  - Seed dispersal by animals is one of the most important plant-animal mutualisms,
      but saurochory, the dispersal of seeds by reptiles, has received little
      attention. We investigated the role of the Florida box turtle (Terrapene carolina
      bauri) as a seed dispersal agent in pine rockland forests of the lower Florida
      Keys and examined the effect of turtle digestion on seed germination. We obtained
      seeds of 11 species with fleshy fruits and 2 species with non-fleshy fruits (a
      grass and legume) from the feces of 145 box turtles collected on Key Deer
      National Wildlife Refuge from 1999 to 2000. We planted the seeds of nine species
      and germination percentage (percentage of seeds that germinated during the
      experiment) varied from 10% to 80%. Comparative germination experiments were
      conducted with Thrinax morrissii, Serenoa repens, and Byrsonima lucida. We
      compared the germination percentage and germination rate (number of days from
      planting to seedling emergence) of seeds from three treatments (seeds recovered
      from feces, control seeds with pulp, and control seeds without pulp) and
      continued these experiments for up to 2 years. Passage through the box turtle
      digestive tract greatly enhanced the germination percentage and germination rate
      of S. repens, but decreased the germination percentage of B. lucida and T.
      morrissii, and decreased germination rate for T. morrissii. Subsequent
      destructive seed viability tests revealed that many ungerminated T. morrissii
      seeds remained viable, suggesting long-term seed dormancy may occur, even after
      passage through the turtle digestive system. In addition, the proportion of
      ungerminated seeds which remained viable was greater for seeds recovered from
      turtle feces than from control seeds with pulp. Furthermore, removal of fleshy
      pulp either manually or by the turtle digestive system may allow T. morrissii to
      escape insect predation.

PMID- 14685846
TI  - Dietary effects on life history traits in a terrestrial isopod: the importance of
      evaluating maternal effects and trade-offs.
AB  - Studies of life history aim to explain patterns in the evolution of reproductive
      investment, growth, and survival. Trade-offs between traits are a fundamental
      component of life history theory. In herbivorous arthropods life history traits
      are often responsive to variation in numerous environmental factors, especially
      diet quality. Using three artificial diets under controlled laboratory
      conditions, we examined changes in life history traits (i.e. growth rate,
      offspring number, offspring size, incubation period), trade-offs between traits,
      and maternal effect on the growth rate of offspring, in the common woodlouse
      (terrestrial isopod), Porcellio laevis. The high protein diet had significant
      impacts on offspring production, triggering a smaller-sized offspring, and
      demonstrating a trade-off between these last two traits. The high carbohydrate
      diet seldom exerted a significant effect on incubation period. The quality of
      dietary items evidently has important consequences on the life history of the
      mother and, thus, on offspring growth; the directions of these effects, however,
      were opposite. Mothers fed diets with high protein concentrations presented
      significant maternal effects, measured as offspring growth rate during later
      ontogeny. Our results support the notion that protein, rather than carbohydrate,
      concentrations in the diet limit herbivorous arthropods, and have significant
      consequences on life history traits, as was seen for P. laevis. Clearly, the
      change in phenotypic correlations between incubation period and offspring number
      from negative to positive is an empirical demonstration of the context dependence
      of life history trait trade-offs.

PMID- 14685847
TI  - Experimental separation of resource quantity from temporal variability: seedling
      responses to water pulses.
AB  - We tested the hypothesis that higher temporal variability in water supply will
      promote higher species richness of germinating and surviving seedlings using
      assemblages of 70 species of herbaceous plants from limestone pavement habitats.
      In a two-factor greenhouse experiment, doubling the total volume of water added
      led to greater germination (measured as number of germinated seeds and species)
      and establishment (survival and biomass) but the effects of temporal variability
      depended on the response variable considered. Low pulse frequencies of water
      addition with total volume added held constant resulted in greater temporal
      variability in soil moisture concentration that in turn promoted higher density
      and richness of germinated seedlings. Low pulse frequencies caused an eight-fold
      greater mortality in the low total volume treatment and biomass production to
      decline by one-third in the high total volume treatment. The effects of
      increasing temporal variability in water supply during recruitment stages can
      thus be opposite on different components of plant fitness and may also depend on
      total resource quantity. While greater species richness in more temporally
      variable soil moisture conditions was attributable to sampling effects rather
      than species-specific responses to the water treatments, species relative
      abundances did vary significantly with temporal variability. Changes in the
      amplitude or frequency of resource fluctuations may alter recruitment patterns,
      and could have severe and relatively rapid effects on community structure in
      unproductive ecosystems.

PMID- 14685848
TI  - Black-tailed prairie dogs and the structure of avian communities on the
      shortgrass plains.
AB  - We tested the hypothesis that black-tailed prairie dogs (Cynomys ludovicianus)
      influence avian community structure on the shortgrass prairie. We surveyed 36
      prairie dog towns and 36 paired sites without prairie dogs during summer and fall
      of 1997, 1998, and 1999 in the Oklahoma Panhandle. Our surveys totaled 9,040
      individual observations for 73 avian species. Significantly distinct avian
      communities were present on prairie dog towns when compared to sites within four
      different macrohabitats of the surrounding landscape: open rangeland,
      scrub/sandsage (Artemisia filifolia) habitats, Conservation Reserve Program (CRP)
      plots, and fallow crop fields. Relative densities of all bird species combined
      was higher on prairie dog towns versus paired sites in summer and fall. Mean
      species richness of birds was significantly higher on prairie dog towns than
      paired sites during summer, but there were no significant differences in fall.
      Open rangeland had the highest mean species richness in fall. Assemblages of
      avian communities differed significantly between prairie dog towns and the four
      macrohabitat types during summer. Burrowing owls (Athene cunicularia), killdeer
      (Charadrius vociferous), horned larks (Eremophila alpestris), and meadowlarks
      (Sturnella spp.) were positively and significantly associated with prairie dog
      towns during summer, while horned larks and ferruginous hawks (Buteo regalis)
      were significantly associated with prairie dog towns during fall. Even in their
      current remnant state, black-tailed prairie dogs continue to play a significant
      role in the assembly of ecological communities across the Great Plains.
      Conservation of prairie dogs goes well beyond a single species, and is an
      important strategy for the preservation of the prairie ecosystem as a whole.

PMID- 14685849
TI  - Damaging UV radiation and invertebrate predation: conflicting selective pressures
      for zooplankton vertical distribution in the water column of low DOC lakes.
AB  - In nature most organisms have to manage conflicting demands of food gathering,
      predator avoidance, and finding a favorable abiotic environment (oxygen,
      temperature, etc.) in order to maximize their fitness. In the vertical water
      column of lakes with high solar ultraviolet radiation (UV) and invertebrate
      predators, zooplankton face two particularly strong and conflicting selective
      pressures. During daylight hours invertebrate predators often induce an upward
      vertical migration of zooplankton prey while potentially damaging UV forces a
      downward migration. We used 2.2 m long columns suspended vertically in a lake to
      conduct 2x2 factorial experiments to examine patterns of depth selection behavior
      by zooplankton in the presence and absence of both the invertebrate predator
      Chaoborus and UV. We hypothesized that Chaoborus and UV both affect the
      distribution of zooplankton and a combination of both factors would lead to a
      narrowing of depth distribution. We found that when Chaoborus were present
      zooplankton tended to be distributed at shallower depths in the columns, while in
      the presence of UV they exhibited a deeper distribution. Chaoborus themselves
      were always found near the bottom of the columns regardless of the UV treatment.
      Simultaneous exposure to predators and UV resulted in a peak of zooplankton
      (especially Daphnia catawba) distribution at intermediate depths. In a
      significant number of cases, depth range was narrowed in response to Chaoborus,
      UV, or both.

PMID- 14685852
TI  - Acute liver failure associated with Coxsackie virus B2 infection in a neonate.

PMID- 14685850
TI  - A decade's studies on metastasis of hepatocellular carcinoma.
AB  - Metastasis remains one of the major challenges before hepatocellular carcinoma
      (HCC) is finally conquered. This paper summarized a decade's studies on HCC
      metastasis at the Liver Cancer Institute of Fudan University. We have established
      a stepwise metastatic human HCC model system, which included a metastatic HCC
      model in nude mice (LCI-D20), a HCC cell line with high metastatic potential
      (MHCC97), a relatively low metastatic potential cell clone (MHCC97L) and several
      stepwise high metastatic potential cell clones (MHCC97H, HCCLM3, and HCCLM6) from
      their parent MHCC97 cell. Endeavors have been made for searching human HCC
      metastasis-related chromosomes/proteins/genes. Monogene-based studies revealed
      that HCC invasion/metastasis was similar to that of other solid tumors, and the
      biological characteristics of small HCC were only slightly better than that of
      large HCC. Using comparative genomic hybridization (CGH), fluorescence in situ
      hybridization (FISH), genotyping, cDNA microarray, and 2-dimensional gel
      electrophoresis, we obtained some interesting results. In particular, in
      collaboration with the National Institute of Health (NIH) in the United States,
      we generated a molecular signature that can classify metastatic HCC patients,
      identified osteopontin as a lead gene in the signature, and found that genes
      favoring metastasis progression were initiated in the primary tumors. We also
      found that chromosome 8p deletion, particularly in the region of 8p23, was
      associated with HCC metastasis. Cytokeratin 19 was identified as one of the
      proteins, which was found in MHCC97H, but not in MHCC97L cells. Experimental
      interventions using the high metastatic nude mice model have provided clues for
      the prevention of HCC metastasis. Translation from workbench to bedside
      demonstrated that serum VEGF, microvessel density, and p53 scoring may be of
      value for the prediction of postoperative metastatic recurrence. Interferon alpha
      proved effective for the prevention of recurrence both experimentally and
      clinically. In conclusion, HCC metastasis that probably initiated in the primary
      tumor is a multigene-involved, multistep, and changing process. The further
      elucidation of the mechanism underlying HCC metastasis will provide a more solid
      basis for the prediction and prevention of the metastatic recurrence of HCC.

PMID- 14685854
TI  - Contiguity and contingency in action-effect learning.
AB  - According to the two-stage model of voluntary action, the ability to perform
      voluntary action is acquired in two sequential steps. Firstly, associations are
      acquired between representations of movements and of the effects that frequently
      follow them. Secondly, the anticipation or perception of an acquired action
      effect primes the movement that has been learnt to produce this effect; the
      acquired action-effect associations thus mediate the selection of actions that
      are most appropriate to achieve an intended action goal. If action-effect
      learning has an associative basis, it should be influenced by factors that are
      known to affect instrumental learning, such as the temporal contiguity and the
      probabilistic contingency of movement and effect. In two experiments, the
      contiguity or the contingency between key presses and subsequent tones was
      manipulated in various ways. As expected, both factors affected the acquisition
      of action-effect relations as assessed by the potency of action effects to prime
      the corresponding action in a later behavioral test. In particular, evidence of
      action-effect associations was obtained only if the effect of the action was
      delayed for no more than 1 s, if the effect appeared more often in the presence
      than in the absence of the action, or if action and effect were entirely
      uncorrelated but the effect appeared very often. These findings support the
      assumption that the control of voluntary actions is based on action-effect
      representations that are acquired by associative learning mechanisms.

PMID- 14685853
TI  - Non-alcoholic fatty liver disease: an emerging pathological spectrum.
AB  - The spectrum of pathological lesions observed in non-alcoholic fatty liver
      disease (NAFLD) is wide and strongly resembles that of alcohol-induced liver
      disease. It ranges from fatty liver to steatohepatitis, progressive fibrosis and
      cirrhosis. Hepatocellular carcinoma is a possible complication of NAFLD, but
      whether it is related to frequently associated metabolic disorders (e.g.,
      overweight, diabetes) or to underlying cirrhosis is unclear. This disease is the
      result of a multi-factorial process in which insulin resistance seems to play a
      major role in the initial accumulation of fat in the liver, whereas multiple
      causes of mitochondrial dysfunction and oxidative stress can induce the secondary
      occurrence of necroinflammatory lesions and fibrosis. Genetic factors might
      explain why only some patients with simple steatosis will develop steatohepatitis
      and fibrosis. Due to the increasing prevalence of obesity in Western countries,
      NAFLD will possibly be a public health problem and the liver disease of the
      future.

PMID- 14685855
TI  - A short history of ideo-motor action.
AB  - The ideo-motor theory, which is currently receiving heightened interest in
      cognitive psychology, looks back on a long history. Essentially two historical
      roots can be presented. A British one, initiated by Laycock (1845) and Carpenter
      (1852), which was developed in order to explain ideo-motor phenomena by means of
      cerebral reflex actions. A second and older root is the German one by Herbart
      (1816, 1825), Lotze (1852), and Harless (1861), which considered the ideo-motor
      principle a fundamental mechanism of all intentional human behaviour. Both roots
      converged in James' (1890) Principles of Psychology before they fell into
      oblivion due to the dominance of behaviorism in the first half of the 20th
      century. The few empirical ideo-motor studies of the early 20th century are
      briefly described. Finally, similarities and differences in the history of the
      ideo-motor theory are delineated and a perspective is given covering research
      questions that could be examined in the future.

PMID- 14685856
TI  - Induction of 3'-O-beta-D-ribofuranosyl adenosine during compatible, but not
      during incompatible, interactions of Arabidopsis thaliana or Lycopersicon
      esculentum with Pseudomonas syringae pathovar tomato.
AB  - All hitherto identified aromatic compounds accumulating in leaves of Arabidopsis
      thaliana (L.) Heynh. upon infection with virulent or avirulent strains of
      Pseudomonas syringae pathovar tomato ( Pst) were indolic metabolites. We now
      report the strong accumulation of a novel type of natural product, 3'-O-beta-D
      ribofuranosyl adenosine (3'RA), exclusively during compatible interactions. In
      contrast to the various indolic metabolites, 3'RA was undetectable in
      incompatible interactions of A. thaliana leaves with an avirulent Pst strain, as
      well as in uninfected control leaves. A similar, strong induction of 3'RA was
      observed in compatible but, again, not in incompatible interactions of Pst with
      its natural host, Lycopersicon esculentum. The strength of the effect and its
      confinement to compatible interactions suggests that it may be applicable as a
      diagnostic tool.

PMID- 14685857
TI  - Enhanced rates of P700(+) dark-reduction in leaves of Cucumis sativus L
      photoinhibited at chilling temperature.
AB  - The changes in electron transport within photosystem I (PSI) were studied in
      detached leaves of Cucumis sativus L. during the course of irradiation with
      moderate white light (300 micromol photons m(-2) s(-1)) at 4 degrees C. When
      intact leaves were exposed to the combination of moderate light and low
      temperature, the amplitude of far-red light-induced P700 absorbance changes at
      820 nm (deltaA(820)), a relative measure of PSI, progressively decreased as the
      light treatment time increased. Almost no oxidation of P700 was noticeable after
      5 h. Methyl viologen accelerated the oxidation of P700 to a steady-state level
      and also increased the magnitudes of deltaA(820) changes in photoinhibited
      leaves, reflecting the rapid removal of electrons from native carriers.
      Photoinhibition under moderate light and chilling temperature also accelerated
      the rate of P700(+) reduction after far-red light excitation as the half-times of
      the two exponential components of P700(+) decay curves decreased relative to the
      control ones. A detailed analysis of the kinetics of P700(+) reduction using
      diuron alone or the combination of diuron and methyl viologen strongly favours an
      increased rate of electron donation from stromal reductants to PSI through the
      plastoquinone pool following photoinhibitory treatment. Importantly, the marked
      acceleration of P700(+) re-reduction is the consequence of the irradiation of
      leaf segments at low temperature and not caused by chilling stress alone.

PMID- 14685858
TI  - Expression of KS-type dehydrins is primarily regulated by factors related to
      organ type and leaf developmental stage during vegetative growth.
AB  - The expression of a gene, designated as DHN10, was analyzed at the protein level
      in two Solanum species. The DHN10 protein displays some consensus amino acid
      sequences of dehydrins, termed K- and S-segments. Unlike most dehydrins, both
      segments occur only in single copies in the DHN10 sequence and the S-segment is
      at a C-terminal position. Database searches revealed that KS-type dehydrins
      constitute a specific subclass distributed in dicotyledons and monocotyledons. In
      Solanum tuberosum L. plants, a high DHN10 abundance was observed under control
      conditions, particularly in flowers, stems, tubers and young developing leaves.
      In other Solanaceae and in barley ( Hordeum vulgare L.), the amount of DHN10 was
      much more elevated in young leaves than in old leaves. DHN10 abundance was
      investigated in two Solanum species subjected to low temperature or to drought.
      Under stress conditions, we observed substantially higher protein levels only in
      mature expanded leaves. These findings clearly indicate that KS-type dehydrins
      are present at a high level in the absence of stress during vegetative growth and
      that their expression is primarily regulated by factors related to organ type and
      to leaf development stage. A potential role for the DHN10 dehydrin during plant
      development and in tolerance to environmental stress is discussed.

PMID- 14685859
TI  - In situ translocation of volicitin by beet armyworm larvae to maize and systemic
      immobility of the herbivore elicitor in planta.
AB  - Volicitin (N-[17-hydroxylinolenoyl]-L glutamine) present in the regurgitant of
      beet armyworm (Spodoptera exigua) activates the emissions of volatile organic
      compounds (VOCs) when in contact with damaged corn (Zea mays L.) leaves. VOC
      emission in turn serves as a signaling defense for the plant by attracting female
      parasitic wasps that prey on herbivore larvae. Chemical tracking of volicitin
      within plants has yet to be reported. Here we present biochemical data that beet
      armyworm regurgitant serves as a vector for the introduction of volicitin to the
      site of leaf damage under natural feeding conditions. Corn seedlings were 14CO2
      labeled in situ, and beet armyworm larvae were allowed to feed on the labeled
      leaves. Herbivore oral secretions collected from late-third-instar larvae
      contained approximately 120 pmol volicitin (0.05 nCi pmol(-1)) per larva. When
      radiochemically labeled larvae were placed on unlabeled leaves, the amount of
      volicitin introduced to the damaged site was approximately 5.0 nCi (calc. 100
      pmol/larvae). The mobility of volicitin in leaves was examined by allowing
      radiolabeled beet armyworms to feed on unlabeled plants. In such tracking
      experiments, radioactivity was not detected in the upper leaves; however, the
      exogenous application of 5 nCi of [U-14C]sucrose to the lower leaf did result in
      subsequent radioactivity being detected in the upper portion of the plant. The
      detection of labeled sucrose with the same radioactivity as that of administered
      volicitin indicated that volicitin was not readily transported to undamaged
      leaves and that volicitin may not directly serve as a mobile messenger in
      triggering the emissions of VOCs systemically.

PMID- 14685860
TI  - Effect of resistance training on Na,K pump and Na+/H+ exchange protein densities
      in muscle from control and patients with type 2 diabetes.
AB  - Ten patients with type 2 diabetes and seven controls were strength-trained with
      one leg for 30 min three times per week for 6 weeks. The training-induced changes
      in the protein densities of the Na,K-pump subunits and the Na+/H+ exchanger
      protein NHE1 were quantified with Western blotting of needle biopsy material
      obtained from trained and untrained legs of both groups. Training increased the
      bench press and knee-extensor force by 77+/-15 and 28+/-1%, respectively, in the
      control subjects, and by 75+/-7 and 42+/-8%, respectively, in the diabetics. In
      the control subjects the Na,K-pump isoform alpha1 was increased by 37% (P<0.05)
      in trained compared to untrained leg, and in the diabetics the alpha1 content was
      45% higher (P=0.052) in trained compared to untrained leg. For the alpha2 isoform
      the corresponding values were 21% and 41% (P<0.05), respectively. The content of
      the beta1 subunit in the control subjects was 33% higher (P<0.05) in trained
      compared to untrained leg, and 47% higher (P=0.06) in trained compared to
      untrained leg in the diabetics. Thus, a limited amount of strength-training is
      able to increase the Na,K-pump subunit and isoform content both in controls and
      in patients with type 2 diabetes.

PMID- 14685861
TI  - Effects of angiotensin II on sustained outward currents in rat ventricular
      myocytes.
AB  - We investigated the effects of angiotensin II (Ang II) on the sustained outward
      current ( I(sus)) and action potential of rat ventricular myocytes using the
      whole-cell patch-clamp technique. Ang II at 30 nM-3 microM inhibited I(sus) with
      an IC(50) of 240 nM, a Hill coefficient of 1.0 and maximum inhibition of 19.4%.
      Ang II-mediated inhibition of I(sus) was voltage independent, was due to a
      decrease in the K(+) current and was abolished by the Ang II type-I (AT(1))
      receptor blocker, valsartan. The protein kinase C (PKC) inhibitors PKC19-36 or
      calphostin C, abolished Ang II-mediated inhibition of I(sus). In contrast,
      pretreatment with the protein kinase A (PKA) inhibitor PKA6-22 (100 microM)
      significantly enhanced the suppression of I(sus) by 1 microM Ang II: (33.7+/-5.1%
      vs. control 17.1+/-2.3%). These results indicate that Ang II inhibits I(sus) via
      the AT(1) receptor and activation of PKC. Ang II significantly prolonged action
      potential duration (APD) when the control APD was lengthened by a Ca(2+) channel
      activator, BAY K8644. In myocytes with a relatively long APD, Ang II may prolong
      APD by inhibiting I(sus).

PMID- 14685862
TI  - Regulation of type IV collagen gene expression and degradation in fast and slow
      muscles during dexamethasone treatment and exercise.
AB  - Glucocorticoids have anti-anabolic effects on many tissues and can cause muscle
      atrophy. However, their effects on type IV collagen gene expression and
      degradation in skeletal muscle have not been studied previously. Rats were
      treated daily with dexamethasone or saline. Half the groups of experimental and
      control animals were also subjected to daily endurance or uphill running exercise
      to determine the possible preventive effects of exercise. After an experimental
      period of 3 or 10 days, the extensor digitorum longus, soleus and tibialis
      anterior muscles were studied. Dexamethasone treatment for 10 days reduced muscle
      weight and type IV collagen mRNA abundance in all muscles. Gene expression of
      matrix metalloproteinase-2 (MMP-2) was decreased in fast muscles. However, the
      effects of this decrease were possibly attenuated by the simultaneous decrease in
      the activity of tissue inhibitor of metalloproteinases (TIMP-2). The amount of
      type IV collagen was not changed during dexamethasone treatment or exercise. The
      regulation of type IV collagen degradation during dexamethasone treatment varied
      between slow and fast muscles. Although endurance running prevented muscle
      atrophy, exercise could not compensate the changes observed in the regulation of
      type IV collagen gene expression and degradation during dexamethasone treatment.

PMID- 14685863
TI  - Eccentric exercise, isokinetic muscle torque and delayed onset muscle soreness:
      the role of reactive oxygen species.
AB  - There is growing evidence that reactive oxygen species (ROS) are involved in the
      muscular damage and soreness that is observed following strenuous or unaccustomed
      exercise. This study investigated the relationship between delayed onset muscle
      soreness (DOMS), muscle function and ROS following downhill running using
      electron spin resonance (ESR) spectroscopy and plasma malonaldehyde (MDA)
      concentrations. Eight physically active male subjects participated in two trials
      consisting of 30 min of running at approximately 65% VO(2max) on the flat (FLA)
      or a 15% downhill (DWN) gradient. Venous blood samples were drawn before,
      immediately after, and then 24, 48 and 72 h post exercise, and at the same time
      DOMS and muscle function were assessed. Blood was analysed for markers of ROS,
      total and differential white blood cell count, and creatine kinase. Muscle
      function was measured on an isokinetic dynamometer, whilst DOMS was assessed
      using a visual analogue scale. An increase in ROS, detected via ESR spectroscopy
      and MDA, was observed following DWN ( P<0.05) but not following FLA. Increased
      DOMS and loss of muscle function were observed following DWN ( P<0.05) but not
      following FLA ( P>0.05). DWN resulted in a transient leukocytosis ( P<0.05)
      occurring immediately post-exercise but returning to pre-exercise levels by 24 h.
      Although DWN resulted in an increase in ROS production, the increase occurred
      after the peak decline in muscle function and DOMS, suggesting that there may be
      a disassociation in the temporal relationship between ROS, loss of muscle
      function and DOMS.

PMID- 14685864
TI  - Measurement and prediction of METs during household activities in 35- to 45-year
      old females.
AB  - This study determined whether four self-paced household tasks, conducted in the
      subjects' homes and a standardised laboratory environment, were performed at a
      moderate intensity [3-6 metabolic equivalents (METs)] in a representative sample
      of thirty-six 35- to 45-year-old females. Energy expenditure was also predicted
      via indirect methods. Self-paced energy expenditure during sweeping, window
      cleaning, vacuuming and mowing was measured using the Douglas bag technique.
      Heart rate, respiratory frequency, Computer Science Applications (CSA) movement
      counts (hip and wrist), Borg rating of perceived exertion and Quetelet's index
      were also recorded as potential predictors of energy expenditure. While the four
      activities were performed at mean intensities >or=3.0 METs in both the home and
      laboratory, all comparisons between these two environments were statistically
      significant ( P<0.001). The 95% confidence intervals (CIs) for the home and
      laboratory prediction equations were +/-1.1 METs and +/-1.0 MET, respectively.
      These data suggest that the aforementioned household chores can contribute to the
      30 min x day(-1) of moderate-intensity activity required to confer health
      benefits. However, the substantial between-subject variability in energy
      expenditure resulted in some persons performing these tasks at a light intensity
      (<3.0 METs). The significant MET differences between the home and laboratory
      emphasise the effects of 'environment and terrain' and the 'mental approach to a
      task' on self-paced energy expenditure. Considering the means for the five
      activities ranged from 3.1 METs to 6.0 METs, the 95% CIs for the regression
      equations lack predictive precision.

PMID- 14685865
TI  - Influence of environmental temperature on exercise-induced inspiratory muscle
      fatigue.
AB  - Exercise in the heat has detrimental effects on circulation that might negatively
      influence endurance performance. If blood is diverted away from the inspiratory
      muscles to the skin during exercise in the heat, exercise-induced inspiratory
      muscle fatigue might be exacerbated. Thus, we hypothesised that prolonged heavy
      endurance exercise in the heat would impair exercise performance and exacerbate
      inspiratory muscle fatigue compared to exercise in a thermo-neutral environment.
      Using a crossover design, seven male endurance trained subjects [mean (SEM)
      maximum oxygen uptake = 62.2 (1.5) ml x kg(-1) x min(-1)] were assigned at random
      to either a group that exercised in the heat at an ambient temperature of 35
      degrees C (H) or a group that exercised in the cool at 15 degrees C (C). Maximum
      inspiratory mouth pressure at zero flow (P(0)), pressure normalised maximum
      relaxation rate (MRR/ P(0)), time constant for the pressure decay (tau), and
      maximum inspiratory flow at 30% P(0) (V(30)) were assessed immediately before and
      reassessed within 2, 30, and 60 min of completing a pre-loaded time trial [40 min
      at 65% peak power, plus approximately 30 min time trial] on a cycle ergometer.
      Group H completed the time trial 432 (135) s slower than group C [2285 (180) vs
      1852 (122) s, respectively; Delta=24 (8)%, P=0.0094]. Repeat measurements within
      2 min post-exercise revealed significant declines in P(0), MRR/ P(0), tau, and
      V(30) from baseline values, but no between-group differences were observed. In
      conclusion, heavy sustained exercise in the heat impaired subsequent time-trial
      performance but did not exacerbate inspiratory muscle fatigue in endurance
      trained subjects.

PMID- 14685866
TI  - Adults have lower stroke rate during submaximal front crawl swimming than
      children.
AB  - The aim of this study was to examine the effects of body size and propelling
      surface size on stroke rate (SR) and stroke length (SL) during front crawl
      swimming. Eleven children [11.7 (0.8) years] and 13 adults [21.4 (3.7) years]
      were compared. A third group of swimmers (n=5) had their propelling surface
      altered experimentally, swimming with hands only and using small- and large-sized
      paddles. Underwater videography was used to analyze four 25-m submaximal and four
      25-m maximal swims for SR, SL, velocity (v) and hand slip. The results showed
      that adults have a lower SR at any submaximal v and a lower slope of the
      relationship between SR and workload (v(3)) compared to children. At 1.0 m s(-1)
      the SR values were 0.38 (0.04) and 0.58 (0.06) cycles s(-1) for adults and
      children respectively ( P<0.01). Adjusting for body size did not change this
      relationship [0.46 (0.05) and 0.67 (0.08) cycles s(-1) at a v of 1.0 bodylength
      s(-1) for adults and children respectively, P<0.001]. SL, adjusted for potential
      anatomical SL, was found to be longer in adults at submaximal velocities but not
      at maximal v. Hand slip was found to be lower for adults [-0.19 (0.14) and -0.36
      (0.18) m for adults and children respectively, P<0.05]. Thirty per cent of the
      variations in slip could be attributed to propelling size. Increased propelling
      surface reduces SR and increases SL. It was concluded that adults have a lower SR
      both at absolute and size relative velocities compared to children; the causes
      could not be attributed to differences in body size, but probably the propelling
      size and swimming technique make the adults more effective swimmers.

PMID- 14685867
TI  - Bovine colostrum supplementation does not affect plasma buffer capacity or
      haemoglobin content in elite female rowers.
AB  - It has been reported that bovine colostrum (BC) supplementation improves buffer
      capacity (beta) during exercise, but whether the improvement results from changes
      in tissue and/or blood buffer systems has not been determined. The purpose of the
      present study was to examine the effect of supplementation with BC on blood
      buffer systems. Thirteen elite females rowers were supplemented with 60 g.day(-1)
      of either BC ( n=6) or whey protein (WP, n=7) during 9 weeks of pre-competition
      training in a randomised, double-blind, placebo-controlled, parallel design. All
      subjects undertook the study as a group and completed the same training program.
      Resting haemoglobin (Hb) concentration and plasma buffer capacity (pbeta)
      (determined by titration with HCl) were measured pre- and post-supplementation.
      There were no differences in macronutrient intakes ( P>0.56) or training volumes
      ( P>0.99) between BC and WP during the study period. There were no differences in
      Hb [BC 13.28 (0.28) mg.dl(-1), WP 13.70 (0.26) mg.dl(-1); P=0.45] or pbeta [BC
      14.8 (1.1) nmol HCl.ml(-1).pH(-1), WP 14.8 (0.5) nmol HCl.ml(-1).pH(-1); P=0.68]
      between groups at week 0. pbeta increased in both groups during the study period
      ( P<0.001), but the increases were not significantly different between groups (
      P=0.52). Hb did not change significantly in either group ( P=0.35). These data
      indicate that supplementation with BC does not affect pbeta or Hb. We therefore
      suggest that adaptations in tissue buffer systems are responsible for the
      previously reported increases in buffer capacity that result from BC
      supplementation.

PMID- 14685868
TI  - The influence of muscle pain and fatigue on the activity of synergistic muscles
      of the leg.
AB  - The purpose of this study was to investigate the effect of experimentally induced
      muscle pain on the motor-control strategies of synergistic muscles during
      submaximal fatiguing isometric contractions. The root mean square (RMS) and
      median frequency (MF) of the surface electromyographic (EMG) signal from
      synergistic plantarflexors and dorsiflexors were assessed to exhaustion. Ten
      subjects performed sustained dorsiflexions and plantarflexions at two contraction
      levels, 50% and 80% of maximum voluntary contraction, with or without muscle
      pain, induced by injection of 6% hypertonic saline in one synergist. In the
      painful contractions, the RMS of the EMG signal was decreased compared to the
      control condition in the initial phase of the contraction, in the muscles where
      pain was induced as well as in the nonpainful synergists. Moreover, the EMG
      signal MF decreased faster during muscle pain than in the control condition. The
      endurance time was shorter during muscle pain, and some of the nonpainful
      synergists showed increased compensatory activity at the end of the contractions
      to maintain the target force. The decreased EMG activation during pain was
      coupled with significantly decreased torque levels during the painful condition
      that would partly explain the results. However, the ratio between force and EMG
      amplitude was decreased for both the painful and nonpainful synergists, so other
      mechanisms might explain the present findings. This study shows that localized
      muscle pain can reorganize the EMG activity of synergists where no pain is
      present. These findings may have implications for the understanding of
      manifestations seen in relation to painful musculoskeletal disorders.

PMID- 14685869
TI  - Endurance training attenuates exercise-induced oxidative stress in erythrocytes
      in rat.
AB  - The aim of this study was to investigate whether endurance training reduces
      exercise-induced oxidative stress in erythrocytes. Male rats (n=54) were divided
      into trained (n=28) and untrained (n=26) 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 x
      day(-1), 5 days a week for 8 weeks, reaching the speed of 2.1 km x h(-1) at the
      fourth week. For acute exhaustive exercise, graded treadmill running was
      conducted reaching the speed of 2.1 km x h(-1) at the 95th min, 10% uphill, and
      was continued until exhaustion. Acute exhaustive exercise increased the
      erythrocyte malondialdehyde level in sedentary but not in trained rats compared
      with the corresponding sedentary rest and trained rest groups, respectively.
      While acute exhaustive exercise decreased the erythrocyte superoxide dismutase
      activity in sedentary rats, it increased the activity of this enzyme in trained
      rats. On the other hand, acute exhaustive exercise increased the erythrocyte
      glutathione peroxidase activity in sedentary rats; however, it did not affect
      this enzyme activity in trained rats. Erythrocyte glutathione peroxidase activity
      was higher in trained groups compared with untrained sedentary group. Neither
      acute exhaustive exercise nor treadmill training affected the erythrocyte total
      glutathione level. Treadmill training increased the endurance time in trained
      rats compared with sedentary rats. The results of this study suggest that
      endurance training may be useful to prevent acute exhaustive exercise-induced
      oxidative stress in erythrocytes by up-regulating some of the antioxidant enzyme
      activities and may have implications in exercising humans.

PMID- 14685870
TI  - The effects of creatine supplementation on muscular performance and body
      composition responses to short-term resistance training overreaching.
AB  - To determine the effects of creatine supplementation during short-term resistance
      training overreaching on performance, body composition, and resting hormone
      concentrations, 17 men were randomly assigned to supplement with 0.3 g/kg per day
      of creatine monohydrate (CrM: n=9) or placebo (P: n=8) while performing
      resistance exercise (5 days/week for 4 weeks) followed by a 2-week taper phase.
      Maximal squat and bench press and explosive power in the bench press were reduced
      during the initial weeks of training in P but not CrM. Explosive power in the
      bench press, body mass, and lean body mass (LBM) in the legs were augmented to a
      greater extent in CrM ( P<or=0.05) by the end of the 6-week period. A tendency
      for greater 1-RM squat improvement ( P=0.09) was also observed in CrM. Total
      testosterone (TT) and the free androgen index (TT/SHBG) decreased in CrM and P,
      reaching a nadir at week 3, whereas sex hormone binding globulin (SHBG) responded
      in an opposite direction. Cortisol significantly increased after week 1 in CrM
      (+29%), and returned to baseline at week 2. Insulin was significantly depressed
      at week 1 (-24%) and drifted back toward baseline during weeks 2-4. Growth
      hormone and IGF-I levels were not affected. Therefore, some measures of muscular
      performance and body composition are enhanced to a greater extent following the
      rebound phase of short-term resistance training overreaching with creatine
      supplementation and these changes are not related to changes in circulating
      hormone concentrations obtained in the resting, postabsorptive state. In
      addition, creatine supplementation appears to be effective for maintaining
      muscular performance during the initial phase of high-volume resistance training
      overreaching that otherwise results in small performance decrements.

PMID- 14685871
TI  - Imaging-based estimates of moment arm length in intact human muscle-tendons.
AB  - The muscle-tendon moment arm length, i.e. the perpendicular distance from the
      muscle-tendon action line to the rotation centre of the joint that the muscle
      tendon spans, is responsible for transforming muscle force and linear
      displacement to joint moment and rotation. In this paper, previous work on in
      vivo measurements of human muscle-tendon moment arms at rest and during isometric
      maximal voluntary contraction (MVC) is reviewed. The results obtained by actual
      measurements on 2-D magnetic resonance images indicate that the moment arm
      lengths of the Achilles and tibialis anterior tendons increase during MVC
      compared with rest by between 22% and 44%, due to (1) joint displacement, (2)
      muscle thickening and (3) stretching of collagenous structures mediating the
      action of tendon. However, moment arm length calculations based on the virtual
      work principle fail to show the above effect. Potentially severe mechanical
      limitations of the latter method as adapted under in vivo conditions raise
      questions about its validity during muscle contraction.

PMID- 14685872
TI  - The many possible roles of stem cells in age-related macular degeneration.

PMID- 14685873
TI  - Management of branch retinal vein occlusion with vitrectomy and arteriovenous
      adventitial sheathotomy, the possible role of surgical posterior vitreous
      detachment.
AB  - BACKGROUND: To analyze the results of vitrectomy and adventitial sheathotomy in
      the management of branch retinal vein occlusion (BRVO). This is a nonrandomized
      interventional case series. METHODS: Patients with BRVO with progressive decrease
      in visual acuity underwent surgery and were prospectively evaluated in two
      centers. Surgical procedure included a 3-port pars plana vitrectomy, removal of
      the internal limiting membrane and arteriovenous crossing sheathotomy. Clinical
      evaluation consisted of best-corrected visual acuity, fluorescein angiography and
      optical coherence tomography. RESULTS: Thirteen eyes were analyzed consecutively.
      An improvement in visual acuity of two ETDRS lines or more was observed in nine
      eyes (69%). The mean gain was 1.9 ETDRS lines. The absence of previous posterior
      vitreous detachment (PVD), poor initial visual acuity and the presence of retinal
      ischemia were correlated to the improvement in vision (P=0.014, P=0.002 and
      P=0.052, respectively). Eyes with initial PVD had a mean loss postoperatively of 
      5.7 lines, but eyes without PVD experienced a gain of 4.2 lines (P<0.001).
      Macular edema decreased significantly (preoperative thickness: 714 micro m,
      postoperative thickness: 353 micro m, P=0.04), whereas the aspect of the vein at
      the crossing and the non-perfused area remained unchanged. CONCLUSION: Vitrectomy
      with sheathotomy seems to be of benefit in the management of BRVO, particularly
      in eyes with no previous PVD, and the main postoperative feature was the decrease
      in macular edema. The surgical detachment of posterior hyaloid could be as
      important (or more) as the sheathotomy itself. Further studies are needed to
      define the most efficient surgical management of BRVO.

PMID- 14685874
TI  - Role of growth factors and the wound healing response in age-related macular
      degeneration.
AB  - Growth factors (GF) are important in several stages of the pathogenesis of age
      related macular disease (AMD). In choroidal neovascularization (CNV) in exudative
      AMD, the GF involved are similar to those involved in wound healing of the skin.
      Like granulation tissue of skin, CNV is characterized by clotting, inflammation,
      angiogenesis and fibrosis, and like in skin wounds, members of the VEGF,
      angiopoietin, PDGF and TGF-beta families of GF are expressed. However, several of
      these GF may also serve physiological functions in the normal eye, where the
      retinal pigment epithelium (RPE) employs them to provide trophic support to the
      neuroretina and choriocapillaris, in addition to maintaining an anti-angiogenic
      state. Derangement of these physiological functions may underlie the initiation
      of CNV in AMD. Basolateral secretion of VEGF-A by the RPE maintains the
      choriocapillaris, and is enhanced by hypoxia. Age-related changes in Bruch's
      membrane lead to impairment of this trophic function and choriocapillaris
      atrophy, as well as to decreased diffusion of oxygen towards the neuroretina. The
      resulting outer retina hypoxia may be an important driving force of CNV
      formation, by stimulating VEGF overexpression by the RPE, in addition to the
      effects of increased oxidative stress and low-grade inflammation. RPE senescence
      and hypoxia may also decrease expression of angiogenesis inhibitors such as PEDF,
      further shifting the balance to a pro-angiogenic state in the aging eye.

PMID- 14685875
TI  - Tamponade properties of double-filling with perfluorohexyloctane and silicone oil
      in a model eye chamber.
AB  - BACKGROUND: The use of perfluorohexyloctane as a heavier-than-water tamponade for
      long-term use is limited by its tendency to dispersion and associated intraocular
      inflammation. Double-filling with silicone oil and F6H8 produces a united, two
      layer bubble, appearing as a single bubble. This has been proposed as a method of
      improving the utility of F6H8 as a tamponade. METHODS: A surface modified
      polymethylmethacrylate model eye chamber was double-filled with
      perfluorohexyloctane and silicone oil to approximate a 90% fill. The proportion
      of silicone oil was increased in a stepwise fashion. A qualitative comparison of
      surface contact at each stage was made. Chambers with one, two or no indent were
      used. Dispersion by agitation of the chamber was assessed. RESULTS: With less
      than 20% silicone oil it was difficult to force the two liquids to make contact.
      With more oil they united in the form of a single bubble joined at an interface.
      Once joined, the sides of the single bubble were drawn away from the wall of the
      chamber. As the proportion of silicone oil increased the area of lost contact
      increased and progressed inferiorly. Compared to F6H8 alone the double-fill
      reduced dispersion. CONCLUSION: Silicone oil and F6H8 can unite to form a single
      bubble that changes the effectiveness of either tamponade agent on their own. The
      double-fill needs to have enough silicone oil to form a single bubble, but this
      needs to be kept as low as possible to avoid progressive loss of lateral
      tamponade. It does not provide good simultaneous superior and inferior tamponade.
      The double-fill reduces dispersion.

PMID- 14685877
TI  - The standard gamble between cataract extraction and AMD.

PMID- 14685876
TI  - Prognostic value of cell-cycle markers in ocular adnexal lymphoma: an assessment
      of 230 cases.
AB  - BACKGROUND: To determine the prognostic value of cell-cycle associated markers in
      ocular adnexal lymphoma (OAL). METHODS: Two hundred sixty-one consecutive cases
      of ocular adnexal lymphoproliferative lesions were subdivided into reactive
      lymphoid hyperplasia (RLH), atypical lymphoid hyperplasia (ALH) and OAL. The
      latter were sub-typed according to the new WHO Lymphoma Classification. All
      lesions were investigated applying standard immunohistochemical methods with
      antibodies specific for pRB, p53, p16, p21, BCL-6 and for multiple myeloma
      oncogene-1-protein (MUM1, also known as IRF4). The main endpoints included the
      development of a local recurrence, of systemic disease and of lymphoma-related
      death. The association of prognostic variables with endpoints was assessed by
      multiple logistic and Cox regression models, respectively. RESULTS: The ocular
      adnexal lymphoproliferative lesions were categorised as OAL ( n=230; 88%), RLH (
      n=29; 11%), and ALH ( n=2; 1%). The major lymphoma subtypes included 136
      extranodal marginal zone B-cell lymphoma (EMZL), 31 diffuse large cell B-cell
      lymphomas, 27 follicular lymphomas, 9 plasmacytomas, 9 lymphoplasmocytic
      lymphoma/immunocytomas and 8 mantle cell lymphomas. The median follow-up time was
      44.5 months. Most OAL patients had Stage IE disease and were treated with
      radiotherapy. Thirty-seven (25%) Stage IE patients had tumour relapses: these
      were significantly associated with an increased BCL6 blast percentage. Sixty-two
      (42%) Stage IE patients developed systemic disease: they had "non-EMZL" with
      large growth fractions and increased blast percentages for BCL6. Fifty-seven
      (25%) OAL patients died because of their lymphoma; lymphoma-related death was
      significantly associated on multivariable analysis with advanced clinical stage,
      an age >60 years and large tumour growth fractions. CONCLUSION: Subtyping of OAL
      according to the new WHO Lymphoma Classification, the stage of disease and tumour
      cell growth fraction aided the prediction of (1) tumour relapse, (2) the
      development of systemic disease and (3) lymphoma-related death in OAL.

PMID- 14685878
TI  - Application of the Voice Handicap Index in 45 patients with substitution voicing
      after total laryngectomy.
AB  - We tested the Voice Handicap Index (VHI) in 45 patients with substitution voicing
      (that is, without the use of two vocal folds), the majority of them using tracheo
      oesophageal speech. We introduced a corrected VHI score (VHI(corr)) whose values
      are in the range from 0 to 100 and which can be expressed as a percentage. As
      such, the VHI(corr) is a handy and transparent tool, and it seems to be suited
      for representing the handicap caused by the voice disorder when some items are
      unanswered as experienced in patients with substitution voicing. Interestingly,
      our data reveal that the voice handicap severity of this particular category of
      patients is (1) moderate and in the range of "common" dysphonia and (2) not
      affected by additional radiotherapy. It seems that the E domain is overstated due
      to the number of problematic items in the P and F domains.

PMID- 14685880
TI  - Thyroid metastasis from rectal adenocarcinoma involving the airway treated by
      crico-tracheal resection and anastomosis: the role of palliative surgery.
AB  - A 59-year-old woman underwent surgical removal of a pT3N3M0 rectal adenocarcinoma
      (RAC) through an abdominal-perineal approach followed by chemoradiotherapy (CHT
      RT) in 1995. She underwent a right inferior lobectomy for a lung metastasis 3
      years later, followed in 2000 by an additional intervention for a second
      metastasis that was treated by a left superior atypical lobectomy and CHT. The
      patient complained 1 year later of dysphagia and an anterior neck mass was found.
      US examination detected a multifocal lesion in the thyroid gland with involvement
      of the strap muscles, which was confirmed by FNAB to be a third RAC metastasis. A
      palliative course of RT was performed, but no regression of the lesion was
      observed. Crico-tracheal infiltration was also suspected after CT scan. The
      patient was in good general condition and strongly favored surgery. In August
      2001 she underwent total thyroidectomy, total parathyroidectomy, strap muscles
      excision, central compartment neck dissection and crico-tracheal resection and
      anastomosis involving the anterior arch of the cricoid between the crico-thyroid
      joints and the first three tracheal rings. She was extubated at the end of the
      surgical procedure with no tracheotomy, started an oral diet the day after, and
      was discharged without complications 9 days later. She was followed up monthly by
      endoscopy and has undergone one CT and two MR scans at 6-month intervals. The
      patient had no RAC recurrence in the neck when last seen 26 months after surgery.
      During this time, she underwent four further lung metastasectomies followed by
      CHT.

PMID- 14685881
TI  - Outpatient laser tonsillar ablation under local anaesthetic.
AB  - Outpatient laser ablation of the palatine tonsils under local anaesthetic is an
      alternative technique to capsular tonsillectomy for recurrent tonsillitis under
      general anaesthetic. Laser tonsillotomy ablates up to 70% of the tonsillar tissue
      and is performed when patients choose not to have a conventional tonsillectomy,
      or are unfit for a general anaesthetic. The technique described here is an
      adaptation of Krespis' laser-assisted serial tonsillectomy (LAST) whereby only
      one sitting is required. Krespis' technique effectively eliminates recurrent
      tonsillitis in 96% of the cases over a 4-year follow-up period and represents the
      only substantial study looking at treating recurrent tonsillitis with outpatient
      laser ablation. This study is a retrospective postal survey of 19 patients who
      underwent laser tonsillar ablation under local anaesthetic for recurrent chronic
      tonsillitis from 1997 to 2001 and was performed in liaison with the clinical
      audit department at Basildon Hospital. We had a response rate of 74% and an
      admission rate of 0%, which compares favourably with day case tonsillectomy
      surgery. Of the patients, 75% did not experience further episodes of tonsillitis
      12 months after the procedure and 77% of the patients were glad they had the
      operation. Although this technique does not completely eliminate tonsillitis, it
      offers an alternative for those patients who prefer a procedure that is done
      quickly in an outpatient setting without the additional problems of general
      anaesthesia, overnight hospital admission and long waiting lists.

PMID- 14685882
TI  - The value of screening for multiple arterio-venous malformations in hereditary
      hemorrhagic telangiectasia: a diagnostic study.
AB  - Occult visceral arterio-venous malformations (AVMs) may be a constant threat to
      patients suffering from hereditary hemorrhagic telangiectasia (HHT), also known
      as Rendu-Osler-Weber syndrome (M. ROW). HHT patients predominantly become
      symptomatic through chronic, recurrent epistaxis, a symptom that can alert
      physicians at an early stage of the disease. The purpose of this study was to
      investigate whether occult, visceral arterio-venous malformations could be
      detected by screening imaging studies in patients suffering from HHT. In a
      comprehensive diagnostic study, Rendu-Osler-Weber patients were examined for
      potential visceral arterio-venous malformations by physical examination and non
      invasive imaging techniques. The Department of Otolaryngology of the Philipps
      University of Marburg is a major referral center and coordinated the screening
      procedures. Thirty-five individuals with the presumed diagnosis of HHT gave
      informed consent to the screening investigations. Eighteen of 35 individuals were
      found to suffer from visceral vascular malformations; most of the AVMs were
      diagnosed in the lung, but also the liver, spleen, brain and eyes were affected.
      Six patients could be treated preventively by arterial embolization for AVMs of
      the lung, liver and brain. Comprehensive screening for occult AVMs in HHT
      patients seems to be justified to avert potential complications in this group of
      patients.

PMID- 14685884
TI  - Familial antrochoanal polyposis--a case report.
AB  - Antrochoanal polyps are rare lesions. Since Killian's first report in 1906,
      several pathogenic mechanisms have been described. However, the aetiological
      factors are still not fully understood. In this paper we present the first report
      of antrochoanal polyps occurring in siblings, suggesting a possible familial
      aetiology.

PMID- 14685886
TI  - Alterations in rhinosinusal homeostasis in a sportive population: our experience
      with 106 athletes.
AB  - The aim of the present work was to analyse the alterations of rhino-sinusal
      physiology in 106 professional athletes (swimmers, skiers, boxers and runners)
      using objective rhinological methods. Every athlete underwent an accurate
      anamnesis, a complete objective ORL evaluation, an active anterior
      rhinomanometry, an acoustic rhinometry and an evaluation of mucociliary transport
      time (MCTt). Skiers were also submitted to a nasal decongestion test (NDT). In
      swimmers, the mean MCTt was 27.4+/-4.97 min (normal value: 13+/-3 min; P<0.0001).
      The average MCTt for the skier group was 19.58+/-1.92 min ( P<0.0001); the mean
      value of total basal nasal resistance was 0.37+/-0.05 Pa/ml per s (normal value
      =0.25 Pa/ml per s; P<0.001). After NDT, total nasal resistance was 0.18+/-0.02
      Pa/ml per s. In the group of boxers, the total mean nasal resistance was 0.64+/
      0.05 Pa/ml per s ( P<0.001); the mean cross-sectional area at the nasal valve
      level was 0.57+/-0.04 cm(2) (normal value =0.55+/-0.05 cm(2)) and at the inferior
      turbinate level 0.83+/-0.05 cm(2) (normal value =0.4+/-0.04 cm(2); P<0.001); the
      TMC average time was 27.35+/-2.21 min ( P<0.0001). Finally, for the runners, the
      mean MCT time was 20.56+/-2.35 min ( P<0.001). Knowing the alterations of the
      physiological nasal respiration is of extreme importance to develop a correct and
      timely therapeutic approach to be able to restore rhino-sinusal homeostasis.
      Athletes, in fact, need the earliest therapeutic aid in order to avoid the
      interference of prolonged rhino-sinusal alterations with their performance and
      also to avoid a more serious clinical situation concerning the inferior airways.

PMID- 14685889
TI  - Asymptomatic ileal perforation of an intrauterine device.
AB  - CASE REPORT: A 43-year old para three woman had a total abdominal hysterectomy
      for severe menorrhagia. During the procedure, a copper intrauterine contraceptive
      device (IUD) 'TCu 380A' was found extruding from within the small bowel lumen and
      partly perforating into the posterior uterine wall. The apparent insertion of the
      IUD was asymptomatic and she remained asymptomatic for a period of 8 years prior
      to presentation. CONCLUSION: This is a report of an asymptomatic perforation into
      the ileum discovered during a hysterectomy after an asymptomatic period of 8
      years in situ.

PMID- 14685887
TI  - Positron emission tomography using [18F]fluorodeoxyglucose (FDG-PET) in the
      clinically negative neck: is it likely to be superior?
AB  - The capability of modern imaging techniques such as CT, MRI, US and US-guided
      fine-needle aspiration cytology (USgFNAC) to detect small tumour deposits is
      limited. Therefore, the detection of occult metastases in the clinically negative
      neck remains a diagnostic problem. One of the novel options to refine staging of
      head and neck cancer is [(18)F]fluorodeoxyglucose positron emission tomography
      (FDG-PET). To evaluate the diagnostic value of FDG-PET in the detection of occult
      malignant lymph nodes, we compared the results of FDG-PET with other diagnostic
      techniques and the histopathological outcome of 15 neck dissection specimens from
      15 head and neck cancer patients with a clinically negative neck. Three sides
      contained metastases of squamous cell carcinoma. FDG-PET enabled detection of
      metastases in two sides, which were also detected by MRI or USgFNAC. FDG-PET and
      CT missed metastases in one patient, which were detected by both MRI and USgFNAC.
      In studies with a detailed examination of lymph nodes of a neck dissection, a low
      sensitivity of FDG-PET for the detection of occult lymph node metastases is
      found. It is unlikely that FDG-PET is superior in the detection of occult lymph
      node metastases in head and neck cancer patients with a palpably negative neck.
      The histopathological method used seems to be the most important factor for the
      differences in sensitivity in reported FDG-PET studies. New approaches such as
      the use of monoclonal antibodies labelled with a positron emitter may improve the
      results of PET in these patients.

PMID- 14685890
TI  - Peripartum cardiomyopathy and cesarean section: report of two cases and
      literature review.
AB  - INTRODUCTION: The anesthetic management of labor and delivery in patients with
      peripartum cardiomyopathy is not well defined. Using continuous spinal anesthesia
      with bupivacaine or combined spinal epidural anesthesia with ropivacaine in such
      rare clinical situations has not been previously reported. CASE REPORT: We
      present two cases in which parturients with the diagnosis of peripartum
      cardiomyopathy presented in congestive heart failure for emergent Cesarean
      section. Continuous spinal anesthesia and combined spinal-epidural anesthesia
      were successfully employed as the anesthetic techniques for the procedures. Both
      patients remained hemodynamically stable during surgery and were discharged home
      on postoperative days 5 and 4 respectively.

PMID- 14685891
TI  - Comparison between spontaneous ovarian hyperstimulation syndrome and hyperreactio
      luteinalis.
AB  - CASE REPORT: We present here two patients with bilateral ovarian enlargement
      during the first trimester of pregnancy. We clinically diagnosed one case as
      spontaneous ovarian hyperstimulation syndrome and the other case as hyperreactio
      luteinalis. CONCLUSION: It may be difficult to discriminate severe hyperreactio
      luteinalis in the first trimester from spontaneous ovarian hyperstimulation.

PMID- 14685893
TI  - Semen quality of smoking and non-smoking men in infertile couples in a Turkish
      population.
AB  - OBJECTIVE: This retrospective study was designed to reveal the effect of smoking
      on semen parameters in an infertile Turkish population. PATIENTS: Two hundred and
      ninety-six infertile males were triaged as nonsmokers, light smokers and heavy
      smokers. Semen volume; sperm density, motility and morphology were the main
      outcome measures. RESULTS: Rapidly progressing sperm ratio of the heavy smokers
      group was greater than that of the light smokers group (p<0.05). Morphologic
      evaluation results revealed better results for the nonsmokers than the heavy
      smokers in terms of tail anomalies and percent of coiled tails (p<0.05)
      CONCLUSIONS: In infertile Turkish men, heavy smoking was found to have
      detrimental effects on tail of the spermatozoon. Interestingly, heavy smokers
      have a higher percent of rapidly progressive sperm with respect to light smokers.
      Prospective studies will help determining the definite effect of smoking on semen
      quality.

PMID- 14685894
TI  - The impact of advanced maternal age (> or = 40 years) on birth outcomes among
      triplets: a population study.
AB  - OBJECTIVE: The objective was to determine the impact of advanced maternal age on
      the birth outcomes of triplet gestations. STUDY DESIGN: A retrospective cohort
      study on 15,795 triplets born in the United States from 1995 to 1997. The
      generalized estimating equations framework was used to generate relative risks
      after capturing the effect of sibling correlations within triplet clusters.
      RESULTS: There was a 40% higher likelihood for stillbirths among older gravidas
      (> or = 40 years) as compared to younger mothers (20-29 years) although this was
      statistically non-significant. By contrast, we noted a significantly lower level
      of neonatal mortality (OR=0.36, 95% CI=0.19-0.67), perinatal mortality (OR=0.53;
      95% CI=0.32-0.89) and infant mortality (OR=0.37; 95% CI=0.20-0.67) among older
      mothers. CONCLUSION: Our findings demonstrate a "shifting phenomenon" whereby a
      higher level of intra-uterine demise was compensated by a higher rate of extra
      uterine survival among triplets born to older mothers.

PMID- 14685895
TI  - Neuropathological evaluation of the diencephalon, basal ganglia and upper
      brainstem in alobar holoprosencephaly.
AB  - Holoprosencephaly (HPE) is caused by the impaired cleavage of the embryonic
      prosencephalon, and in the severest type, alobar HPE, the normally bilateral
      diencephalon and basal ganglia are fused and tend to incorporate into the upper
      brainstem. The detailed neuropathological features of HPE remain to be
      elucidated, although disturbed regulation in body temperature and electrolyte
      balance are frequently observed. We immunohistologically examined the expression
      of hypothalamic hormones, neurotransmitters, calcium-binding proteins and
      neuropeptides in six female autopsy cases of alobar HPE. Eight age-matched
      controls formed the comparative basis for the immunoreactivity of these markers
      during the fetal period. Neurons immunoreactive for either vasopressin or orexin
      A were noted in the fused diencephalon in five HPE cases, and colocalization of
      vasopressin and tyrosine hydroxylase occurred in HPE cases surviving more than 6
      months. Tyrosine hydroxylase-immunoreactive fibers and neurons were observed in
      the fused diencephalon and basal ganglia in all the six cases. Parvalbumin
      immunoreactive structures were identified in the fused diencephalon and basal
      ganglia in five cases, and the apparent red nucleus was identified by anti
      parvalbumin immunostaining in two cases aged more than 1 year. Five cases
      demonstrated substance P-immunoreactive structures in the diencephalon, and a
      substantia nigra-like structure in the midbrain was visualized by immunostainings
      for both tyrosine hydroxylase and substance P in four cases. Only two cases aged
      more than 1 year had immunoreactivity for methionine-enkephalin in the basal
      ganglia and substantia nigra. These data suggest that the fused diencephalon and
      basal ganglia exhibited functional developments in alobar HPE, and the disturbed
      expression of the markers may be involved in hypothalamic and/or motor
      abnormalities in patients.

PMID- 14685896
TI  - Diagnostic accuracy of benign eyelid skin lesions in the minor operation theatre.
AB  - PURPOSE: To determine the accuracy of the clinical diagnosis of benign eyelid
      skin lesions in a minor operation theatre (MOT) setting. METHODS: This study was
      carried out prospectively over a 6-month period. Subjects attending the minor
      operation theatre set-up with eyelid skin lesions were assessed and lesions were
      labelled as benign, pre-malignant or malignant. All patients underwent excision
      biopsy of the lesion. Histopathologic diagnosis was obtained for each lesion,
      which was then matched with the respective clinical diagnosis. The Diagnostic
      Accuracy (DA) was calculated for benign lesions using the formula proposed by
      Lightstone et al. RESULTS: Two hundred eyelid skin lesions from 183 consecutive
      patients were included in the study. Clinically, 187 lesions were labelled as
      benign, 12 as malignant and 1 as pre-malignant. The histopathologic report
      matched with the clinical diagnosis in 192 cases (96%). However, incorrect
      diagnoses included 3 malignant and 3 pre-malignant lesions that were labelled as
      benign clinically. The DA for benign lesion was 95.7%. CONCLUSION:
      Histopathologic confirmation may be necessary for most cases in the MOT.

PMID- 14685897
TI  - Hertel exophthalmometry: reliability and interobserver variation.
AB  - PURPOSE: To quantify and analyze the interobserver variation in Hertel
      exophthalmomety and to evaluate the impact of experience on it. METHODS: In a
      population-based epidemiologic study, Hertel exophthalmometry was performed on
      1063 randomly selected normal subjects (stratified sampling) by an oculoplastic
      attending surgeon (A) and a third-year ophthalmology resident (R). Both observers
      were masked to the reading of the other. The Chi-square test, two-tailed paired
      sample t-test, and two-tailed paired independent t-test were used to analyze the
      data (SPSS Release 9.0, Chicago). RESULTS: There were 463 (43.5%) females and 600
      (56.5%) males. The age ranged from 6 to 70 years (mean +/- SD = 20.3 +/- 10.9).
      The mean right eye protrusion was 14.8 mm for both 'A' and 'R'. The mean left eye
      protrusion was 14.6 mm and 14.7 mm, respectively. There was good correlation (r =
      0.80) and no statistically significant difference (0.1 < P < 0.6) for the ocular
      protrusion values (right, left, and average) measured by 'A' and 'R'. However,
      the percentage agreement (within +/-1 mm limits of acceptance) was about 60%.
      Comparison of the first 530 subjects versus the remaining cases showed no
      improvement in agreement with the senior observer. CONCLUSION: Hertel
      exophthalmometry is a reliable method for measuring the ocular protrusion.
      However, as with most clinical measures, there is a negligible interobserver
      variation that seems to be unavoidable.

PMID- 14685898
TI  - Factors affecting the success of external dacryocystorhinostomy.
AB  - PURPOSE: To assess the success rate of external dacryocystorhinostomy (Ext-DCR)
      and factors affecting it in a university hospital. MATERIALS AND METHODS: In a
      retrospective interventional non-comparative case series, records of 276 Ext-DCRs
      in 274 patients in a 9-year period were reviewed. 'Complete success' was defined
      as patent system on irrigation (objective) and absence of symptoms (subjective).
      Patent system on irrigation with minimal postoperative symptoms was considered as
      partial success. The chi-square and Fisher's exact tests with 95% confidence
      interval (CI) were used to analyze the data (SPSS release version 9.0, Chicago).
      RESULTS: The age range was 3-84 years (mean: 41.5, SD: 17.7). The majority of the
      patients (66.7%) were female. The most common presumed etiology was primary
      acquired nasolacrimal duct obstruction (PANLDO) (227/276, 82.2%). A silicone tube
      was inserted in 111 patients (40.2%). Follow-up was from 6 to 89 months (mean:
      11.5, SD: 10.4). Overall complete success rate was 89.1% (246/276). It was 92%
      (209/227) in PANLDO, 72.7% (16/22) in congenital NLDO (P: 0.01, 95% CI: 0.024
      0.030), 71.4% (10/14) in traumatic NLDO (P: 0.001, 95% CI: 0.012-0.017), 90%
      (9/10) in previous failed DCR (P: 0.6, 95% CI: 1), and two out of three patients
      with previous nasal/sinus surgery. Gender, type of presenting symptoms, duration
      of preoperative symptoms, silicone tube insertion in PANLDO, and associated
      canalicular stenosis did not have a significant effect on the success.
      CONCLUSION: Ext-DCR is an effective and highly successful procedure for the
      treatment of NLDO regardless of the etiology.

PMID- 14685899
TI  - Expression of HLA class I, beta(2)-microglobulin and HLA class II antigens in
      primary orbital melanoma.
AB  - Major histocompatibility antigens (MHC) play a crucial role in the recognition of
      tumor cells by the immune system. There is not much information on the role of
      MHC molecule expression in primary orbital melanomas. In the present study, the
      authors examined the expression of human leukocyte antigen (HLA) class I, beta(2)
      microglobulin (beta(2)-m) and HLA class II antigens in primary orbital melanoma
      and correlated this with the clinical and pathological findings. HLA class I
      antigen, beta(2)-m and HLA class II antigen expression were evaluated
      immunohistochemically in three primary orbital melanomas and correlated with cell
      type and metastasis. Immunohistochemistry showed heterogeneous expression of HLA
      class I, beta(2)-m and HLA class II antigen in two cases with no liver metastasis
      and negative expression in one case with liver metastasis. This preliminary
      observation deserves further investigation, which may shed more light on the
      immune escape mechanisms of this tumor and thus make possible novel therapeutic
      strategies.

PMID- 14685900
TI  - Loss of antigen-processing molecules in primary orbital melanoma.
AB  - OBJECTIVE: To study the antigen-processing molecules in primary orbital melanomas
      and correlate them with the clinicopathological features. METHODS AND MATERIALS:
      Antigen-processing molecules comprising the low molecular weight proteins LMP2
      and LMP10, transporter associated with antigen-processing TAP1, the binding
      protein tapasin and the chaperone protein calnexin were analyzed by
      immunoperoxidase staining with monoclonal antibodies in three primary orbital
      melanomas. The results were correlated clinicopathologically. RESULTS: The three
      primary orbital melanomas were composed of spindle cells. LMP2, LMP10, TAP1,
      tapasin and calnexin were heterogeneous in the two cases with no hepatic
      metastasis and negative in one case with hepatic metastasis. CONCLUSIONS: Antigen
      processing molecules are decreased in orbital melanomas with increasing
      aggressiveness. This could have important implications for immunotherapy. This
      preliminary observation deserves further investigation, which may shed more light
      on the immune escape mechanisms of this tumor and thus make possible novel
      therapeutic strategies.

PMID- 14685901
TI  - The subjective experience of early postoperative pain following retrobulbar
      anaesthesia for enucleation and primary orbital implant.
AB  - INTRODUCTION: We performed a prospective audit of the level of postoperative pain
      experienced by patients following enucleation with insertion of a primary orbital
      implant after preincisional regional retrobulbar anaesthesia using bupivacaine
      0.75% with 1:100,000 adrenaline. MATERIALS AND METHODS: An 11-point numerical
      ranking box scale was used to measure the subjective experience of postoperative
      pain following enucleation with insertion of a primary orbital implant in 40
      patients with uveal melanoma. Surgery was performed under general anaesthesia
      with a supplementary peroperative retrobulbar injection of bupivacaine
      0.75%/adrenaline 1:100,000. Pain scores were measured for the first 8 hours
      following administration of the block. RESULTS: The sample included 19 female and
      21 male patients with a mean age of 66.7 years (31-87). At four hours post block,
      80% were still pain free with 17% experiencing only mild to moderate pain (BS-11
      = 1-4). Thirty-four (85%), twenty-eight (70%) and twenty-seven (67%) patients
      remained pain free at 2, 3 and 4 hours, respectively with no additional
      analgesia. The remainder scored BS-11 of 1-4 in 92% of cases. Twenty percent
      required supplementary analgesia (paracetemol in 78% cases) by 5 hours and 57% by
      8 hours. BS-11 at 8 hours were 0 in 50%, 1-4 in 22% and 5-10 in 10% of patients
      (17% asleep). No complications using this technique were recorded. DISCUSSION:
      Using a preincisional retrobulbar injection of bupivacaine with adrenaline, BS-11
      pain scores remained low with no or minimal additional analgesia for up to 4
      hours post surgery. In combination with oral analgesia, effective pain control
      was provided in most cases for up to 8 hours post block.

PMID- 14685902
TI  - Congenital orbito-palpebral cyst in a case of Fraser syndrome.
AB  - A seven-year-old girl was referred to our clinic with absent eyelids and a mass
      which was gradually increasing in size from the right orbit. The child was
      diagnosed to have Fraser syndrome (cryptophthalmos, abnormal genitalia, mental
      deficiency, renal agenesis and abnormal ears). On examination, there was
      cryptophthalmos and a cystic swelling arising from the right orbit. The cyst was
      removed. On gross examination, there was a posterior eyeball with normal optic
      nerve. Placed in the anterior part of the eyeball was a cyst measuring about 2 cm
      in diameter filled with a yellow-coloured fluid. The cavity of the eyeball was
      communicating with the cyst. The cyst wall was lined by a single layer of
      epithelium. The posterior eyeball had well developed sclera, choroid, retina and
      optic nerve. There have been many reports of cryptophthalmos in Fraser syndrome.
      The most common eye deformity described with cryptophthalmos is microphthalmia or
      anophthalmia. To the author's knowledge, there is one other report of cystic
      eyeball with cryptophthalmos in the literature. The cyst seems to be due to a
      surface ectodermal anomaly, rather than a neuro-ectodermal anomaly where there is
      failure of invagination of the primary optic cup during development. The cyst
      wall in those cases has inverted retinal elements. In our case, differentiation
      of retinal elements was present in the posterior eyeball. The abnormality seemed
      to lie in the derivatives of surface ectoderm, namely the eyelids and the
      anterior segment structures.

PMID- 14685903
TI  - Suicide attempt with a 'BIC' pen.

PMID- 14685904
TI  - Dentigerous cyst in the maxillary sinus: a rare cause of nasolacrimal
      obstruction.
AB  - The main types of maxillary cysts are antral mucoceles, retention cysts,
      pseudocysts, dentigerous cysts and keratocysts. Despite the theoretical
      possibility of maxillary sinus cysts leading to nasolacrimal duct obstruction,
      only two cases have been reported in the literature so far. The present authors
      report this rare presentation of a dentigerous cyst with a tooth in the roof of
      the maxillary sinus, which led to nasolacrimal duct obstruction.

PMID- 14685905
TI  - Chloroma of the orbit in a non-leukemic adult: A case report.
AB  - Granulocytic sarcoma has been reported as an isolated lesion in non-leukemic
      patients. However, the majority of these subjects develop acute leukemia within a
      mean interval of 10.5 months from the time of diagnosis. We present a case of
      granulocytic sarcoma of the orbit in a non-leukemic patient who was treated with
      chemotherapy and is doing well after a 2-year period. Patients who do not develop
      leukemia have a better prognosis. Appropriate treatment is delayed in most cases
      because of a high rate of misdiagnosis.

PMID- 14685906
TI  - Primary orbital calcified synovial sarcoma: a case report.
AB  - A 32-year-old woman presented with a progressively increasing recurrent swelling
      of the left eye. An orbital tumor was detected and histologically classified as a
      synovial sarcoma, confirmed by immunohistochemistry and electron microscopy.
      Isolated cases of synovial sarcoma have been reported in the retroperitoneum,
      mediastinum, pharynx and orofacial region. However, the orbit is an extremely
      rare site. The authors report a case of recurrent primary orbital calcified
      synovial sarcoma in a young lady treated with surgery and radiotherapy.

PMID- 14685907
TI  - Malignant teratoma of the orbit: a clinicopathological study of a case.
AB  - PURPOSE: To present a case of malignant sarcomatous changes in an orbital
      teratoma with clinicopathological correlation. MATERIALS AND METHODS:
      Retrospective interventional case report. RESULTS: A 10-month-old child presented
      with protrusion of the left eye of 8 months duration. Computerized tomography
      (CT) revealed a heterogeneous retrobulbar mass in the left orbit. Fine needle
      aspiration biopsy (FNAB) revealed sarcomatous cells. The child was treated with
      chemotherapy and radiotherapy with a provisional diagnosis of sarcoma. However,
      as the proptosis worsened, a repeat CT scan showed a possibility of an
      intracranial extension. Exenteration was done. Histopathological examination
      revealed a teratoma with (malignant) sarcomatous changes. The child is doing well
      at 3 years follow-up with no recurrences. CONCLUSION: Orbital teratomas should be
      considered in the differential diagnosis of all neonatal orbital masses. Although
      rare, malignant changes can occur in teratomas. FNAB is not helpful in the
      diagnosis. Surgical excision of the mass is recommended for a definitive
      diagnosis. Although the prognosis of orbital teratoma is good, there is always a
      chance of vision loss.

PMID- 14685908
TI  - Atypical lipoma: well-differentiated liposarcoma of the orbit with
      dedifferentiated areas.
AB  - Primary orbital liposarcoma is a very rare orbital tumor and dedifferentiation in
      the liposarcomas occurs rarely. Dedifferentiation is defined by development, in a
      well-differentiated tumor, of poorly differentiated, high-grade areas. The
      dedifferentiated liposarcomas (DDLS) have a better prognosis than pleomorphic
      sarcomas as a whole. The treatment of DDLS patients proves to be complicated due
      to the fact that the histopathological diagnosis usually becomes evident only
      after the surgery. In the present paper, the clinical presentation,
      histopathological features, radiological characteristics and clinical treatment
      of one case of well-differentiated liposarcoma with dedifferentiated areas,
      abruptly delimited from the well-differentiated adipocytic component, are
      reported.

PMID- 14685909
TI  - Primary orbital plasmacytoma: A case report.
AB  - A 50-year-old man presented with a fungating growth in the left eye of 3 months
      duration. Biopsy of the mass followed by light microscopy was suggestive of
      plasmacytoma and the diagnosis was confirmed by immunohistochemical stains, which
      demonstrated monoclonality to kappa light chains. Systemic investigations ruled
      out a multiple myeloma. The patient received radiotherapy; however, due to a
      residual mass, the left orbit had to be exenterated. Solitary plasmacytomas may
      not always be completely radiosensitive and radical surgery may be required in
      such cases. Immunohistochemical stains for kappa and lambda light chains can
      prove useful in confirming the diagnosis of suspected plasmacytomas.

PMID- 14685910
TI  - DCR with and without excision of the posterior mucosal flap.

PMID- 14685915
TI  - [Socially underprivileged children--a challenge for communal health care].

PMID- 14685916
TI  - [Initial examination for school attendance in Mannheim: language development at
      initial school entry level].
AB  - INTRODUCTION: In autumn 2001 the initial examination for school attendance in
      Mannheim has been fundamentally reorganised. The individual examination elements
      had been widely standardized, the results can be evaluated by regions and a
      diagnosis for the early detection of legasthenia has been developed. METHODS: The
      testing involved repeating sentences, numbers and artificial words. This has been
      developed by the Pedagogical University Heidelberg. In pre-examinations in
      Heidelberg the results relate significantly to the subsequent results in reading
      and writing. PROBANDS: A total of 2,744 children (46.1% girls, 53.9% boys) aged
      of 5 to 7 years was seen. 71.5% of the children were German nationality. Most non
      German nationalities were Turkish (15.4%) and Italian (3.6%) children. Besides
      the nationality the mother tongue has been also recorded. More than 96% of the
      children had been attending a kindergarten. For judgement of the social strata
      the frequency of social welfare receivers has been recorded. RESULTS: The testing
      results are significantly influenced by the native language and the social strata
      of the children. The results of children with German as native language are above
      those of non-Germans. Within the migrant children there are significant
      differences between the several nationalities. Children from a lower social
      strata achieved lower results. A positive effect to the language development is
      attributed to the attendance of a kindergarten. CONCLUSION: These results are the
      basis for language- and general health supporting projects in Mannheim. For the
      examination for school attendance in the current year the diagnostic for language
      development has been extended by some more aspects.

PMID- 14685917
TI  - [The importance of language development for the success in school for children
      from immigrant families].
AB  - Almost 46% of the foreign pupils leaving vocational training colleges do not take
      their final exams. This alarming trend, which can be observed nationwide, raises
      the question as to which conditions are crucial for the school career of children
      and teenagers of immigrant families and which conditions affect their success at
      school. Attitudes have been influenced by the assumption that by extending the
      length of stay of the immigrant families the problems of integration would
      diminish; consequently it could be assumed that unhindered access to the
      institutions of education would automatically promise success. This expectation
      is mainly responsible for the fact that teaching has not been aligned with the
      specific needs of these children. Extracurricular support, e. g. like helping
      with the homework, was seen as a completion of and support for a school system
      which was considered apt for teaching children from other ethnic backgrounds and
      was not questioned except for special model projects. Precisely these model
      projects demonstrated that all children, both foreign and German, profit from a
      way of teaching which has been adjusted to the intercultural conditions of a
      class rather than denying them. Health care services for youngsters can
      essentially support the process of internal school reforms as doctors point out
      the excessive demands on the immigrated families by traditional teaching, which
      actually impairs the efficiency of performing well at school. Furthermore, health
      care can also explain that the proper development of a child can be impaired if
      its specific learning structures--based on the linguistic and cultural background
      -are ignored by the school.

PMID- 14685918
TI  - [Application of the Breuer-Weuffen Discrimination test as a preschool screening
      test in Baden-Wurttemberg].
AB  - From 1997 to 2002 a total of 597 school children aged 6-7 years and 41,919
      preschool children (5-7 years) were examined using the Breuer-Weuffen
      Discrimination test (DP). For 20 to 23% of all children a further training of
      perceptual and language abilities was found necessary to avoid or reduce learning
      difficulties at school. The DP can be used as a screening method in an average
      time of 7 minutes. The results obtained were well comparable for different
      samples of preschool children. Further, the DP allows the derivation of specific
      needs for the training of children who fail to meet the test criteria. Mild
      perceptual disturbances or light graphomotoric problems can be improved by
      specific training before school offered by parents and kindergarten teachers,
      whereas severe problems should be treated by professionals.

PMID- 14685919
TI  - [Care structures for drug dependent children and adolescents].
AB  - Children and adolescents abusing drugs present a special challenge for our health
      system. Special risks for the development of drug dependence are psychic diseases
      of parents, familial addiction or multiply burdened families. The treatment of
      drug-addicted children and adolescents in child and youth psychiatry requires a
      highly individualised therapy programme as well as a pedagogic and therapeutic
      setting corresponding to age. 745 patients were examined in a retrospective study
      between 1998 and 2001. The results are shown below. 68% of the patients had a
      relevant psychiatric second diagnosis, 39 Patients of the examined drug addicted
      children and adolescents were diagnosed with an additional psychotic disturbance.
      A study of children and youth psychiatry clinics in the fall of 2001 showed that
      sufficient clinical care for drug-addicted children and adolescents is still
      lacking.

PMID- 14685920
TI  - [Workflow involving preventive health care promotes the economic development of a
      company].
AB  - Today's working society obviously develops from industrial production to
      knowledge-intensive service. In service-oriented working conditions, the
      importance of the human being as a main performer of economic success increases.
      Thus, the development leads to a changing spectrum of occupational health risks.
      Together with socio-demographic developments, individual strain-oriented health
      disorders connected to one's occupation might endanger an enterprise's capacity
      of performance and innovation as well as its sustainable enterprise development.
      Only healthy, motivated and qualified employees are able and ready to keep their
      creative and customer-oriented potential harnessed and thereby work to the best
      of their ability. Consequently, occupational health gains a more important role
      within the enterprise. Although in many enterprises the benefit contribution of
      preventive work design has not yet been considered that relevant, enterprises
      have realised that a preventive health-oriented work design might help to better
      manage current business challenges. An up-to-date definition of health includes
      the goals of health improvement, personality development as well as a
      comprehensive well-being. Health is a prerequisite and result of a productive
      reflection upon the conditions and challenges of work. Business practice shows
      that a preventive work design should involve an economic benefit for the
      enterprise. If occupational health is seen as a characteristic of quality and a
      prerequisite for sustainable enterprise development, economic potentials of
      preventive work designs will expand considerably.

PMID- 14685921
TI  - [Objectives and activities of the German Federal Working Group on migration and
      public health].
AB  - The 53rd scientific congress of the Federal association of physicians and
      dentists in the public health services addressed the interdependence of migration
      and health under the motto "health unlimited" in May, 2003. Manifold interactions
      between migration and health contribute to the public health services' everyday
      experiences. Immigrants often encounter manifold obstacles to their access to
      health services in Germany. These barriers are often of communicative or
      administrative nature. The system of public health administration and services
      has, by its very nature, opportunities and assignment a special obligation to
      support the immigrant population. The public health services will increasingly
      become guarantors of equal health opportunities in times of cumulative migration
      and social inequalities. In cooperation with the German Federal Commissioner for
      Migration, Refugees and Integration the German Federal Working Group on Migration
      and Public Health acts as facilitator and advocate for health of immigrants to
      Germany since 1994. A very close co-operation with the public health services and
      an interdisciplinary, intercultural, population-oriented and health-promoting
      approach are core elements of the working group that is lobbying the health of a
      multinational population within the borders of Germany.

PMID- 14685922
TI  - [Aliens Act regulations and consequences of inability to travel].
AB  - The question as to whether a foreign national is (un)able to travel or not is
      often in the foreground of the decision-making process concerning a possible
      termination of their stay in the Federal Republic of Germany. Authorities
      responsible for aliens and administrative courts often require accredited medical
      reports to be able to decide whether inability to travel is actually the case.
      There are no clear legal criteria with regard to the definition of this term and
      an explicit provision by law is also missing. In cases where the decision has
      been made against inability to travel (i.e. a person is said to be able to
      travel), there may be considerable risks for the person concerned. Where the
      decision has been made in favour of inability to travel (i.e. the person is said
      to be unable to travel), a protective system based on the Aliens' Act takes
      effect. This article gives an overview of the legal consequences arising from a
      determined inability to travel; the legal difficulties with regard to the
      definition of this term; and the requirements to be made concerning clarity of a
      prognosis regarding possible risks. The pertinent legislation as well as opinions
      expressed in expert literature are presented.

PMID- 14685923
TI  - Access to health care of illegal (undocumented) immigrants in The Netherlands.

PMID- 14685924
TI  - [SARS surveillance--did it meet the demands made on the surveillance of new
      infectious diseases?].
AB  - INTRODUCTION: The world-wide outbreak of severe acute respiratory syndrome (SARS)
      in the spring of 2003 highlighted the importance of reliable surveillance for
      infectious diseases. The aim of this investigation is to identify possibilities
      for the improvement of the German surveillance system based on the experiences
      made during the SARS epidemic 2003. METHODS: The RKI has established two linked
      databases for the surveillance of SARS, to store case-based data on SARS and to
      keep a record of inquiries by the public health system. Based on these data we
      evaluated the information flow for the surveillance of SARS mainly qualitatively.
      RESULTS AND DISCUSSION: With occurrence of the first SARS case in Germany a
      nationwide surveillance system for SARS was established. Since Germany was
      exclusively confronted with imported SARS cases, the surveillance system could
      fulfil the requirements. It is unclear, however, whether the current procedures
      are sufficient to manage larger epidemics of emerging diseases. For this task the
      public health system needs a uniform electronic information management system
      which allows rapid adaptation to the epidemic situation and is able to deal with
      a large amount of data.

PMID- 14685925
TI  - [Infection surveillance in North Rhine-Westphalia--standard reports, barometer
      and early warning system].
AB  - The increasing significance of communicable diseases requires new surveillance
      tools. Modern electronic instruments in analysis and communication replace the
      former "handbased" statistics and allow the development of early warning systems.
      In North Rhine-Westphalia (NRW) the Institute of Public Health started an
      approach to develop a modular surveillance system prior to the the implementation
      of the new German infectious disease protection act. The first module called
      "Automated infectious disease notifications and information system (AIM+)"
      generates various standard hypertext reports which are published as "Infectious
      disease reports NRW" on the internet (www.loegd.nrw.de). In addition the
      infectious disease information is linked with a geographical information system
      (GIS) giving spatial and temporal patterns. The second module called "Infectious
      disease barometer NRW" offers a quick actual overview highlighting several
      selected diseases. It can be electronically sent out to any interested person.
      The third module "Early warning system" realizes an effective early detection
      system by combining six statistical procedures with a total of 11 separate
      methods. In case of detecting clusters and outbreaks it automatically generates
      warning reports to the responsible parties. All three modules together improve
      the epidemiological surveillance of the population in NRW, support the
      translation of information to prevention and control measures, and therefore
      strengthen epidemiological policy-making.

PMID- 14685926
TI  - [From the second European drinking water guideline to the new drinking water
      regulations].
AB  - The new drinking water regulations, effective 1.1.2003, introduced several new
      and hygienically important changes. The term "drinking water" has changed to
      "water for human consumption". The change of the term gives a remarkable
      extension of the scope of the drinking water regulations. One of the consequences
      is that the water in buildings in which the water is delivered to the public has
      now to be controlled as well. The planned measures may help to promote good
      consequences in case of accidents. The need for treatment makes it necessary to
      control raw water to a higher degree than before. In case of microbial
      contamination the water has to be treated by filtration. Disinfection may no
      longer be the only treatment to ensure a safe drinking water supply. The
      adherence to the technical rules demanded by the new drinking water regulations
      may convey much additional security to water supply.

PMID- 14685927
TI  - [Surveillance and testing of domestic installations according to the new drinking
      water regulations].
AB  - Effective 1.1.2003 the new drinking water regulation (TrinkwV2001) was enacted.
      For public health authorities new tasks result, for example the monitoring of
      house installations with supply of drinking water for the public, in particular
      in hospitals, old person nursing homes, kindergartens, schools, hotels,
      restaurants etc. Public health authorities are obligated to establish a monitor
      programme on the basis of suitable controls by random sampling. The
      investigations of drinking water are to extend to at least the parameters, which
      can change in the house installation unfavourably. In view of the multiplicity of
      the plants which can be supervised the question arises, how far public health
      authorities can conscientiously fulfil their monitoring obligation. The Ministry
      of Health MFAS of Lower Saxony initiated country-wide a working group developed
      for a pattern administrative regulation, which, revised by the
      "Landerarbeitsgemeinschaft Umweltbezogener Gesundheitsschutz" LAUG, has been
      published in some Lands of the German Federal Republic with changes. The pattern
      administrative regulation plans to examine hospitals and old person nursing homes
      at least 1 x annually, schools and kindergartens every 5 years, other communal
      facilities, sport and leisure facilities, hotels and restaurants after a risk
      evaluation by random sampling at least however one plant per 10,000 inhabitants.
      Restaurants in stations, ports and airports are to be controlled at least once
      annually. The drinking water investigation is to extend to micro-biological
      parameters, like E. coli, coliform germs, germs tested at 22 degrees C and 36
      degrees C as well as the chemical parameters copper and lead. The investigation
      on Legionella pneumophila in the warm-water system can be arranged in individual
      cases. In this article the considerations for these defaults are described, and
      pointers to a practicable risk assessment are given.

PMID- 14685928
TI  - [Pseudomonads in a new hospital building].
AB  - Testing the piping of a new hospital showed that the drinking water was
      contaminated with Pseudomonas aeruginosa. Because of pollution the plumbing
      system was treated with oxidizing biocides and air-water flushing for several
      times, unfortunately without stopping the bacterial recontamination. The reasons
      were firstly stagnation due to dead legs in the piping system, oversized pipes,
      very low water exchange rates and the installation of a catch water system,
      secondly low flow velocity because of low water pressure. After these sources of
      recontamination had been repaired, chlorine dioxide sanitization could be stopped
      successfully

PMID- 14685929
TI  - Predictors of community women's osteoporosis prevention intention--a pilot study.
AB  - The main purpose of this pilot study was to identify the predictors of community
      women's osteoporosis prevention intention. The osteoporosis assessment scales
      were self-developed and contained 5 scales: a demographics scale, a health status
      scale, an osteoporosis health belief scale (OHBS), a knowledge scale, and a
      prevention intention scale. The content validity of the five scales ranged
      from.90 to 1.00. Test-retest was used to examine the reliability of the
      demographic characteristics scale and the health status scale, which ranged
      from.9 to 1.0. Meanwhile, the reliability coefficients of the OHBS comprising
      perceived susceptibility, perceived seriousness, perceived benefit, and perceived
      barrier were .75, .90, .80, and .72. In this pilot study, the coefficient of KR
      20 for osteoporosis knowledge was .88. The value of Cronbach 's Coefficient Alpha
      for prevention intention was .85. The results of this research were : (1) The
      averaged scores of the OHBS comprising perceived susceptibility, perceived
      seriousness, perceived benefit, and perceived barrier were 2.8 (SD = 0.5), 2.2
      (SD = 0.7), 1.9 (SD = 0.4), and 2.9 (SD = 0.7). Meanwhile, the averaged score for
      women's knowledge on osteoporosis was 10.0 (SD = 2.8). The averaged score for
      women's intentions for the prevention of osteoporosis was 2.5 (SD = 0.6). (2)
      There were some significant correlations between OHBS and demographics, health
      status, knowledge, and prevention intention. (3) Knowledge was positively
      correlated with perceived barriers, prevention intention, age, self-rated score
      for health, breast feeding time, and amount of calcium intake. (4) Prevention
      intention was positively correlated with knowledge, number of children, age of
      fracture, and hormone replacement therapy. (5) The major factors influencing
      intention for community women were, in order, knowledge, educational level (high
      school graduate), number of children (n = 2), self-rated health score, experience
      of bone density examination (yes), hormone replacement therapy (yes), and
      kyphosis (yes). These seven items accounted for 45.8% of the variation in
      intention. The results of this pilot study can help community health
      professionals evaluate, implement and improve community women's health beliefs
      regarding prevention of osteoporosis.

PMID- 14685930
TI  - A qualitative inquiry of Taiwanese children's pain experiences.
AB  - Little information was found in studying Taiwanese children's pain experiences.
      Because pain is culturally shaped, health care providers should not assume
      Taiwanese children's pain to be identical to those of children in the US. Thus, a
      qualitative descriptive study with semi-structured interview of 90 hospitalized
      Taiwanese children with acute pain was conducted to understand Taiwanese
      children's pain experiences. Krippendorff's (1980) content analysis was used to
      guide the data analysis. Seven themes from the interview data were presented,
      including definition of pain, quality of pain, previous pain experiences, pain
      expectation, pain acceptance, causes of pain and meaning of pain. Surprisingly,
      the results of this study revealed few differences in the experiences and
      meanings of pain. Most results are consistent with the studies done in the US.
      Differences are minor, including the interpretation of children's crying and how
      Taiwanese parents talk with their children about pain, and are probably related
      to the sample sizes and methodology of the studies. Further research is necessary
      about the influence of culture upon children's pain experiences.

PMID- 14685931
TI  - Effects of LI4 and BL 67 acupressure on labor pain and uterine contractions in
      the first stage of labor.
AB  - Acupressure is said to promote the circulation of blood and qi, the harmony of
      yin and yang, and the secretion of neurotransmitters, thus maintaining the normal
      functions of the human body and providing comfort. However, there has been little
      research-based evidence to support the positive effects of acupressure in the
      area of obstetric nursing. The purpose of this study is to determine the effect
      of LI4 and BL67 acupressure on labor pain and uterine contractions during the
      first stage of labor. An experimental study with a pretest and posttest control
      group design was utilized. A total of 127 parturient women were randomly assigned
      to three groups. Each group received only one of the following treatments, LI4
      and BL67 acupressure, light skin stroking, or no treatment/conversation only.
      Data collected from the VAS and external fetal monitoring strips were used for
      analysis. Findings indicated that there was a significant difference in decreased
      labor pain during the active phase of the first stage of labor among the three
      groups. There was no significant difference in effectiveness of uterine
      contractions during the first stage of labor among the three groups. Results of
      the study confirmed the effect of LI4 and BL67 acupressure in lessening labor
      pain during the active phase of the first stage of labor. There were no verified
      effects on uterine contractions.

PMID- 14685932
TI  - The decision-making experience of mothers selecting waterbirth.
AB  - Waterbirth has been a way of birth for 20 to 30 years abroad, while in Taiwan,
      only in the past three years have some women chosen water birth. This study aims
      to explore the decision-making experience of mothers selecting waterbirth. A
      phenomenological approach was employed in this study. Nine mothers who had given
      birth in water successfully in the midwife clinic in the past year were chosen
      and one-by-one, face-to-face interviews were conducted. The research tools
      included a basic information questionnaire, a semi-structured and open-ended
      interview guide, and an audio recorder to record the entire interviews. The
      content of the interviews was faithfully transcribed and analyzed with Giorgi's
      phenomenological method and Lincoln and Guba's qualitative credibility. Four main
      concepts concluded from the experience context of the studied women were: (1)
      Dissatisfaction with existing obstetric practices; (2) Demonstration of autonomy;
      (3) Consideration of relatives' attitude; and (4) Employing strategies to achieve
      goals. The result of this study can help nursing staff and the public to
      understand the decision-making experience of mothers selecting waterbirth, and
      help the contemplation of health care providers with respect to furnishing a more
      humanized birth environment in hospitals.

PMID- 14685933
TI  - Exercise motivation and processes of change in community-dwelling older persons.
AB  - Although exercise is important for the health of older persons, many older
      persons fail to participate in exercise. Knowledge and skills about changing
      exercise behavior is needed for health professionals to develop appropriate
      interventions to engage older persons in exercise. The purpose of this study was
      to determine how exercise processes of change were used by community-dwelling
      older persons to engage in exercise. A cross- sectional correlational design was
      employed. Cluster sampling was used to obtain potential subjects. A sample of 167
      older persons participated in the study. The age of the participants ranged from
      65 to 89 years (M = 73.7, SD = 6.14). Each participant was interviewed face-to
      face with the investigator reading the questions and marking the answers on the
      Exercise Stages of Change Questionnaire and the Exercise Processes of Change
      Questionnaire. The results revealed that half of the older persons were
      underactive or inactive. One- way ANOVAs and Scheffe post-hoc analyses revealed
      that 10 processes of change were significantly different among the stages of
      change (all p values <.05). The study findings provide guidance in designing
      exercise interventions to increase compliance of older persons with exercise.

PMID- 14685934
TI  - Perceived enactment of autonomy and related factors among elders.
AB  - This study aims to investigate the perceived enactment of autonomy (PEA) of
      Chinese elders as well as its relationship to other variables, such as morale,
      life satisfaction, need for assistance, subjective overall health status, etc.
      Selected demographic attributes (gender, age, living arrangements, etc.) were
      also examined for their relationship to PEA. A purposive sample of 324 subjects
      over 64 years old was recruited from homes and long-term care facilities in
      southern Taiwan. A Chinese version of the PEA scale (PEA-CV) and the Revised
      Philadelphia Geriatric Center Morale Scale (R-PGCMS) were used to measure PEA and
      morale. Data were analyzed using SPSS/PC software version 10.0. The results show
      that these elders had high perceived enactment of autonomy (mean = 2.99). Through
      multiple regression analysis, these results also revealed that need for daily
      living assistance, type of living arrangement, scores for morale and marital
      status significantly affected perceived enactment of autonomy among Chinese
      elders. The results suggest that we should help elders recognize possible
      choices, respect the choices they have made, advocate elders' autonomy while
      providing assistance, and design appropriate activities for them so that they
      gain a sense of freedom, individuality and independence. Directions for future
      studies are suggested.

PMID- 14685935
TI  - Establishment of a predictive model of serum glucose changes under different
      exercise intensities and durations among patients with type 2 diabetes mellitus.
AB  - Regular exercise is regarded as one of necessary elements in treating diabetes
      mellitus (DM). The purpose of this study was to investigate the influence of
      different exercise intensities and durations on serum glucose changes after
      exercise in type 2 DM patients and to establish a predictive model of changes in
      serum glucose under different exercise intensities and durations. Thirty-seven
      type 2 DM patients were recruited from four teaching hospitals. A total of 12
      exercise sessions were scheduled according to the results of a graded treadmill
      exercise test. The 12 exercise sessions were designed on the basis of different
      exercise intensities (40%, 60%, and 80% maximal workload) and exercise durations
      (10, 20, 30, and 40 min). Serum glucose level was measured before and after
      exercise. The findings indicate that the main effect of exercise intensity and
      duration was significant, but there was no interaction effect. All four
      variables, including exercise intensity, exercise duration, pre-exercise serum
      glucose levels, and gender, explained 37% of the variance in serum glucose
      changes after exercise. In conclusion, a dose-response relationship between
      exercise amount and serum glucose changes was demonstrated. This is helpful for
      health professionals to teach type 2 DM patients how to predict serum glucose
      response in different exercise situations.

PMID- 14685936
TI  - Continuing education needs and barriers for public health nurses in Aboriginal
      townships in Taitung, Taiwan.
AB  - In the fast-changing arena of health care, it is important for public health
      nurses (PHNs) to receive professional training through continuing education (CE)
      to maintain practice competencies in the community. However, little information
      is currently known about needs for and barriers to CE for PHNs in role
      transition; therefore, the aim of this study was to identify CE needs and
      barriers for 21 PHNs in four Taitung Aboriginal townships where density of
      Aborigines is the highest in Taiwan. Focus group interviews were used to collect
      data. Interview data were then analyzed using the four step processes of data
      analysis suggested by Webb and Kevern (2001). The results indicated that CE for
      PHNs in Taitung was limited. Community assessment, psychological consultation,
      gerontological care, palliative care, statistical analysis and interpretation,
      and emergency care were identified by PHNs as CE needs. For CE barriers, about
      98% of the PHNs indicated that long distance traveling was the main barrier.
      Family factors and inadequate support from administrative leaders were the next.
      It is concluded that establishing local nursing schools, using the Internet to
      provide CE, and planning computer systematic education courses may reduce
      barriers for PHNs in Taitung county.

PMID- 14685937
TI  - Variation in a repeat sequence determines whether a common variant of the cystic
      fibrosis transmembrane conductance regulator gene is pathogenic or benign.
AB  - An abbreviated tract of five thymidines (5T) in intron 8 of the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene is found in approximately 10% of
      individuals in the general population. When found in trans with a severe CFTR
      mutation, 5T can result in male infertility, nonclassic cystic fibrosis, or a
      normal phenotype. To test whether the number of TG repeats adjacent to 5T
      influences disease penetrance, we determined TG repeat number in 98 patients with
      male infertility due to congenital absence of the vas deferens, 9 patients with
      nonclassic CF, and 27 unaffected individuals (fertile men). Each of the
      individuals in this study had a severe CFTR mutation on one CFTR gene and 5T on
      the other. Of the unaffected individuals, 78% (21 of 27) had 5T adjacent to 11 TG
      repeats, compared with 9% (10 of 107) of affected individuals. Conversely, 91%
      (97 of 107) of affected individuals had 12 or 13 TG repeats, versus only 22% (6
      of 27) of unaffected individuals (P<.00001). Those individuals with 5T adjacent
      to either 12 or 13 TG repeats were substantially more likely to exhibit an
      abnormal phenotype than those with 5T adjacent to 11 TG repeats (odds ratio 34.0,
      95% CI 11.1-103.7, P<.00001). Thus, determination of TG repeat number will allow
      for more accurate prediction of benign versus pathogenic 5T alleles.

PMID- 14685938
TI  - Early-onset renal cell carcinoma as a novel extraparaganglial component of SDHB
      associated heritable paraganglioma.
AB  - Hereditary paraganglioma syndrome has recently been shown to be caused by
      germline heterozygous mutations in three (SDHB, SDHC, and SDHD) of the four genes
      that encode mitochondrial succinate dehydrogenase. Extraparaganglial component
      neoplasias have never been previously documented. In a population-based registry
      of symptomatic presentations of phaeochromocytoma/paraganglioma comprising 352
      registrants, among whom 16 unrelated registrants were SDHB mutation positive, one
      family with germline SDHB mutation c.847-50delTCTC had two members with renal
      cell carcinoma (RCC), of solid histology, at ages 24 and 26 years. Both also had
      paraganglioma. A registry of early-onset RCCs revealed a family comprising a son
      with clear-cell RCC and his mother with a cardiac tumor, both with the germline
      SDHB R27X mutation. The cardiac tumor proved to be a paraganglioma. All RCCs
      showed loss of the remaining wild-type allele. Our observations suggest that
      germline SDHB mutations can predispose to early-onset kidney cancers in addition
      to paragangliomas and carry implications for medical surveillance.

PMID- 14685940
TI  - Coronary heart disease: the female heart is vulnerable.
AB  - During the past decade, an overall theme has emerged, validating the exploration
      of gender-based differences in coronary heart disease (CHD) as a basis for
      clinical strategies to improve outcomes for women. Underrepresentation of women
      in most of CHD and lack of gender-specific reporting in many clinical trials
      continue to limit the available knowledge and evidence-based medicine needed to
      devise optimal managements for women with CHD. Control of conventional coronary
      risk factors provides comparable cardioprotection for men and women. Current
      evidence fails to show cardiac protection from menopausal hormone therapy.
      Clinical presentations of coronary heart disease (CHD) and management strategies
      differ between the sexes. Underutilization of proven beneficial therapies is a
      contributor to less-favorable outcomes in women. The contemporary increased
      application of appropriate diagnostic, therapeutic, and interventional
      managements has favorably altered the prognosis for women, particularly when the
      data are adjusted for baseline characteristics. Better education of women during
      office visits, earlier and more aggressive control of coronary risk factors, and
      a greater index of suspicion regarding chest pain and its appropriate evaluation
      may help to reverse the trend of late referral and late intervention. Research
      indicates that behavioral changes on the part of women and reshaping of practice
      patterns by their health care providers may dramatically reduce the number of
      women disabled and killed by CHD each year.

PMID- 14685941
TI  - Hormone replacement therapy and coronary heart disease: results of randomized
      trials.
AB  - A number of lines of evidence have suggested that postmenopausal hormone
      replacement therapy might be useful in the primary and secondary prevention of
      coronary heart disease (CHD). Data from recent randomized trials are consistent
      in showing no overall benefit of hormone replacement therapy as a continuous
      combined regimen of estrogen and a progestin (PERT) in preventing the development
      of CHD or preventing recurrent events or progression of atherosclerosis. The
      randomized trials also raise questions about hormone replacement therapy in the
      form of estrogen alone (ERT) for prevention of CHD and CHD recurrence. Other
      interventions to prevent CHD and decrease morbidity and mortality in women with
      established disease have a strong evidence base. Hormone replacement therapy
      should not be recommended to prevent CHD or CHD recurrence until and unless data
      from randomized trials establish this as a benefit.

PMID- 14685942
TI  - Diagnosis of coronary artery disease in women.

PMID- 14685943
TI  - Mechanisms of genetic arrhythmias: from DNA to ECG.
AB  - A precise balance of ionic currents underlies normal cardiac excitation and
      relaxation. Disruption of this equilibrium by genetic defects, polymorphisms,
      therapeutic intervention, and structural abnormalities can cause arrhythmogenic
      phenotypes leading to syncope, seizures, and sudden cardiac death. Congenital
      defects result in an unpredictable expression of phenotypes with variable
      penetrance, even within single families. Additionally, phenotypically opposite
      and overlapping cardiac arrhythmogenic syndromes can even stem from the same
      mutation. Accordingly, the relationship between genetic mutations and clinical
      syndromes is becoming increasingly complex.

PMID- 14685944
TI  - Current issues in the diagnosis and management of patients with renal artery
      stenosis: a cardiologic perspective.
AB  - Renal artery stenosis most often is caused by atherosclerosis. Although patients
      with renal artery stenosis can be managed conservatively, renal revascularization
      may be indicated, particularly in patients with refractory hypertension on a
      multidrug regimen and patients with declining renal function. Duplex
      ultrasonography of the renal arteries and magnetic resonance angiography are
      currently the most efficient noninvasive methods for the evaluation of renal
      artery stenosis. Selective digital subtraction renal arteriography remains the
      gold standard for the definitive diagnosis. In selected patients undergoing
      coronary studies and angiography immediately after the coronary procedure can be
      efficient. Atherosclerotic renal artery lesions, which commonly affect the renal
      artery ostium, can be treated safely and effectively with balloon-expandable
      stents. Successful angioplasty commonly results in improved control of
      hypertension, but an overall benefit on renal function and/or patient survival
      has not been shown. Generally the risk/benefit ratio of renal artery stenting
      seems favorable, but further randomized studies are needed for evidence-based
      decision making. All patients with atherosclerotic renal artery stenosis should
      receive rigorous secondary prevention measures including platelet inhibitors,
      statins, and beta-blockers.

PMID- 14685948
TI  - A reminder about scholarly integrity.

PMID- 14685949
TI  - Alcohol and other drug disorders, comorbidity, and violence: comparison of rural
      African American and Caucasian women.
AB  - Tremendous health disparities exist across various segments of the United States
      population with rural women particularly at risk. African Americans have higher
      rates of death, disease, and disability than Caucasians. Although prevalence
      rates for alcohol and other drug use vary across studies, African American women
      generally report less use than Caucasians. However, African Americans
      disproportionately experience negative health and social consequence of AOD use.
      The findings of this study provide rare information about substance abuse in
      rural African American women. Specifically, this manuscript reports differences
      between rural African American and Caucasian women (n=267) on AOD use, comorbid
      Axis I disorders, and violence.

PMID- 14685950
TI  - Healing traumatizing provider interactions among women through short-term group
      therapy.
AB  - A short-term, cognitive group therapy intervention method (Insight: A cognitive
      enhancement program for women) to reduce or resolve ongoing psychological
      disruption and/or trauma was tested among women who experienced traumatizing
      provider interactions (TPI) in their childbearing experience. The sample included
      nine married, Caucasian women, ages 26-45, college educated; one to five children
      (n=19). Birth Perception; Posttraumatic Childbirth Stress; and Traumatizing
      Provider Interaction scores among 19 births confirmed perinatal psychological
      trauma. Descriptive and statistical comparisons for UCLA Loneliness Scale III,
      Coopersmith Self-Esteem Scale, Spielberger's State-Trait Anxiety Index and Beck
      Depression Inventory II, revealed marked psychological improvement in
      postintervention measurements.

PMID- 14685951
TI  - The effects of patient education in lithium therapy on quality of life and
      compliance.
AB  - The purpose of this study was to show the effects of education on medication
      compliance, symptom level and quality of life of outpatients who were being
      treated with lithium for bipolar disorder. The study was performed comparing a
      total of 26 patients (14 study and 12 control) who were a patient group in
      lithium therapy. In the study one group was given a short education program about
      the disorder and lithium therapy in three sessions. Data were collected from both
      groups using a medication knowledge form, Brief Symptom Inventory, and WHO
      Quality of Life Scale before and after the intervention. At the end of 3 months
      whereas there was no difference seen in the scores of the control group; the
      study group had an increase in medication knowledge, a decrease in symptom level,
      an increase in quality of life, and a beginning of more regular medication use.
      Findings that were obtained show the importance of education about the disorder
      and medication in increasing the adaptation to society of patients who have
      bipolar disorder.

PMID- 14685952
TI  - Role functioning and symptom remission in women with postpartum depression after
      antidepressant treatment.
AB  - The primary purpose of this pilot study was to compare improvement of symptoms
      and role functioning in women with postpartum depression after 8 weeks of
      treatment with antidepressants. The study was a secondary data analysis from the
      preliminary data of a double blind, randomized clinical trial. The participants
      (n=61) were primarily Caucasian and slightly over half were married, first time
      mothers, and middle- to upper-middle-class. At intake, most participants were
      moderately to severely ill. At week one and week eight of the study, measures of
      symptoms and functioning were only moderately correlated. After 8 weeks of
      antidepressant treatment, symptoms and most measures of functional status
      improved; however, improvement in one dimension did not imply improvement in the
      other. Recommendations are given for clinical practice and further research in
      this area.

PMID- 14685953
TI  - Trauma, culture and meaning: central issues for mental health nursing.

PMID- 14685954
TI  - The new neighbor: experiences of living next door to people suffering from long
      term mental illness.
AB  - The transition from hospital to community care for people with long-term mental
      illness is of growing concern. The aim of the present study was to illuminate if
      and how people with long-term mental illness have affected their neighbourhood
      after re-establishing themselves in apartments of their own. Nineteen neighbours
      of group homes for people with long-term mental illness, in seven different
      communities in eastern Norway, have been interviewed. The grounded theory
      procedures as well as the constant comparative method were employed to analyse
      the findings. From the data, one main category was identified: the need for
      information.

PMID- 14685955
TI  - Improving geriatric mental health nursing care: making a case for going beyond
      psychotropic medications.
AB  - Providing high-quality mental health nursing care should be an important and
      continuous preoccupation in the gerontological nursing field. As the proportion
      of elderly people in our society is growing, the emphasis on high-quality care
      will receive increasing attention from administrators, politicians, organized
      groups, researchers and clinical nurses. Recent findings illustrate unequivocally
      the important contribution of nurses to achieving the goal of high-quality
      geriatric care. However, the quality of care for the elderly with psychological
      difficulties has not been addressed. The objective of this article is to
      illustrate that while nurses can accomplish much to improve the well-being and
      mental health of the elderly, their skills are often underutilized. Psychotropic
      drugs are often the first-line interventions used by health-care professionals to
      treat mental health concerns of elderly persons. Alternative therapies that could
      be implemented and evaluated, such as psychological counselling, supportive
      counselling, education and life review, are infrequently used. Nevertheless,
      current scientific data suggest that it would be very advantageous if nurses were
      to play a dominant role in the care of elderly people who are depressed or
      experiencing sleep pattern disturbances. The same can be said about elderly
      chronic users of benzodiazepines, as well as those with cognitive impairment.
      Evidence for the use of psychotropic medications as a viable treatment option for
      the elderly both in the community and in the long-term care setting who are
      experiencing mental health challenges is examined. Alternative non
      pharmacological approaches that nurses can use to augment care are also briefly
      discussed.

PMID- 14685956
TI  - Information for assistants of repeated transcranial magnetic stimulation.
AB  - Repeated transcranial magnetic stimulation (rTMS) is an exciting new technology
      being used in psychiatric and neurological research in many centres around the
      world. rTMS has been accepted as a routine treatment of depression in Canada and
      Israel. To this point, it has been exclusively conducted by medical officers. As
      knowledge and experience grows, it is probable that professionals with other
      backgrounds will have the opportunity to play a role. The aim of this paper is to
      provide information that will be valuable to assistants. Electromagnetic
      principles are harnessed to deliver electric currents to localized regions of the
      cortex. rTMS does not involve anaesthesia or seizure. Side-effects appear to be
      few. Much remains uncertain, however, even including the most appropriate
      treatment parameters.

PMID- 14685957
TI  - Application of the cognitive therapy model to initial crisis assessment.
AB  - This article provides a background to the development of cognitive therapy and
      cognitive therapeutic skills with a specific focus on the treatment of a
      depressive episode. It discusses the utility of cognitive therapeutic strategies
      to the model of crisis theory and initial crisis assessment currently used by the
      Community Assessment & Treatment Team of Waitemata District Health Board on the
      North Shore of Auckland, New Zealand. A brief background to cognitive therapy is
      provided, followed by a comprehensive example of the use of the Socratic
      questioning method in guiding collaborative assessment and treatment of
      suicidality by nurses during the initial crisis assessment.

PMID- 14685958
TI  - Burnout and job satisfaction: a comparative study of psychiatric nurses from
      forensic and a mainstream mental health service.
AB  - Within the nursing profession stress and burnout are considered to be widely
      present and problematic. These factors tend to impact negatively on job
      satisfaction and ultimately affect the retention of nurses. Psychiatric/mental
      health nursing as a specialty is considered to be a highly stressful environment;
      however, there is a paucity of research in this area. The current study adopted a
      survey design to compare forensic psychiatric nurses (n = 51) with psychiatric
      nurses from a mainstreamed mental health service (n = 78) in relation to burnout
      and job satisfaction. Forensic nurses displayed lower burnout and higher job
      satisfaction than their counterparts from the mainstreamed services. These
      findings are surprising in light of the image of forensic psychiatric nursing as
      dangerous and unpredictable.

PMID- 14685959
TI  - Alcohol and drug treatment for women: clinicians' beliefs and practice.
AB  - The present paper reports on the results of a telephone survey of 217 alcohol and
      drug treatment clinicians on their beliefs and practice, in relation to service
      provision for women. Nurses comprised the second largest professional group
      surveyed. Seventy-eight percent of clinicians believed that women's treatment
      needs differed from men's and 74% reported a range of approaches and
      interventions, such as assisting with parenting issues and referral to women-only
      programmes. Several differences emerged in relation to approaches and
      interventions used, depending on clinician gender, work setting and proportion of
      women on clinicians' caseload. Implications for mental health nursing include the
      need to more systematically incorporate gender-based treatment needs into
      practice and undergraduate and postgraduate education and training programmes.

PMID- 14685960
TI  - A survey of threats and violent behaviour by patients against registered nurses
      in their first year of practice.
AB  - The purpose of the present study was to determine the prevalence of aggressive
      behaviours by patients against nurses in the first year of practice, and to
      determine the psychological impact of this behaviour. An anonymous survey was
      sent to registered nurses in their first year of practice. From the 1169 survey
      instruments that were distributed, 551 were returned completed (a response rate
      of 47%). The most common inappropriate behaviour by patients involved verbal
      threats (n = 192, 35%), verbal sexual harassment (n = 167, 30%) and physical
      intimidation (n = 161, 29%). There were 22 incidents of assault requiring medical
      intervention and 21 incidents of participants being stalked by patients. Male
      graduates and younger nurses were especially vulnerable. Mental health was the
      service area most at risk. A most distressing incident was described by 123 (22%)
      of respondents. The level of distress caused by the incident was rated by 68 of
      the 123 respondents (55%) as moderate or severe. Only half of those who described
      a most distressing event indicated they had some undergraduate training in
      protecting against assault or in managing potentially violent incidents (n = 63
      of 123; 51%). After registration, 45 (37%) indicated they had had such training.
      The findings of this study indicate priorities for effective prevention
      programmes. The issues highlighted need to be addressed in undergraduate nursing
      curricula and in the development of orientation programmes supporting new
      graduates.

PMID- 14685961
TI  - De-escalating aggression and violence in the mental health setting.
AB  - Aggressive and violent incidents in the health-care setting are increasing
      phenomena around the world. The evidence from current literature suggests that
      changes in health-care access, nursing staff shortages and patient acuity are
      some of the possible causes. De-escalation is a valuable intervention that can be
      used by nurses to help counter the growing problems of aggression and violence.
      The de-escalation project, discussed in the present paper, aimed to explore de
      escalation as an important therapeutic process and is an event of considerable
      potential in the management of aggression and violence. While de-escalation is
      not a new tool, particularly in the mental health-care setting, an educative
      programme aimed at renewing nurses' knowledge and skills in de-escalation is a
      timely project. The final de-escalation kit included a large glossy poster, a
      nursing staff survey, an in-service education session and a literature-based
      discussion paper. The de-escalation kit can be of considerable benefit to those
      nurses who are transient within the workplace, such as casual and agency nurses.

PMID- 14685962
TI  - Grief as a transformative experience: weaving through different lifeworlds after
      a loved one has completed suicide.
AB  - Using Heidegger's hermeneutic phenomenology informed by van Manen's and Benner's
      work, this research is an exploration and interpretation of the lived experiences
      of family members since they lost a close family member to suicidal death. Data
      from in-depth interviews with six participants, the researcher's journal entries
      and published literature were analysed. Findings gave rise to a grief model where
      suicide survivors moved through four modes of being-in-the-world characterized by
      13 lifeworlds or themes. Surviving suicide was a transformative process that in
      time enabled survivors to discover new ways of understanding and relating to the
      world. The findings have implications for nurses and counsellors working in the
      area of suicide bereavement.

PMID- 14685963
TI  - Wound exudate: composition and functions.
AB  - Wound exudate is all too often perceived as a clinical management problem. While
      this can be the case, it should be recognized that exudate does fulfill an
      important function in the healing process. Gradual acceptance of the benefits of
      moist wound healing, combined with the current goals of the 'ideal' moist
      environment, focuses attention on the role of exudate. This review is intended to
      define the components and functions of 'normal' exudate and differentiate it from
      abnormal exudate.

PMID- 14685964
TI  - Hydropolymer dressings in the management of wound exudate.
AB  - In the UK the so-called 'foam' dressings are currently the most widely used
      absorbent dressings. They can, in certain cases, be particularly useful for the
      management of exuding wounds. One type of foam dressing--the Tielle hydropolymer
      adhesive dressing family (by Johnson & Johnson Wound Management)--is a range of
      five types of hydropolymer dressings: Tielle Original dressing, Tielle Lite
      dressing. Tielle Plus dressing, Tielle Borderless dressing and Tielle Packing
      dressing. The Tielle range shares a common basic composition that gives each
      dressing bacterial barrier properties and the capability of managing exudate by
      the combined process of absorption and moisture vapour transmission. Each type
      except Packing can be used as either a primary or as a secondary dressing. The
      choice should be based on the characteristics of the primary dressing, if any, on
      the degree of exudate that the wound is producing and on the condition of the
      surrounding skin. This article aims to give an overview of the Tielle range and a
      review of research-based clinical and scientific evidence to support the
      management of differing levels of exuding wounds in everyday clinical practice.

PMID- 14685966
TI  - What will you do with your time?

PMID- 14685967
TI  - ADA Access Recognition Award goes to Dr. Howard Cassada.

PMID- 14685965
TI  - TIELLE Plus fluid handling capacity can lead to cost savings.
AB  - The cost of care plays an increasing role in treatment decisions. As the costs of
      wound care are largely driven by the costs associated with nurse visits to change
      patients' dressings, attempts to reduce the number of dressings used and thus the
      frequency of nurse visits should be welcomed. The acquisition cost of the
      dressing alone is a poor indicator of the total cost of care. Other factors-
      especially factors influencing the frequency of nurse visits, such as wear time-
      need to be considered when making treatment and formulary decisions. This paper
      assesses the theoretical wear time of a number of dressings based on laboratory
      data on their fluid-handling capacities. The monthly treatment cost associated
      with each dressing is based on the theoretical wear time. The results suggest
      that the superior fluid-handling capacity of TIELLE Plus hydropolymer adhesive
      dressing can reduce the costs associated with wound care.

PMID- 14685968
TI  - Shaping the future of dentistry.

PMID- 14685969
TI  - A helping hand--mentoring.

PMID- 14685970
TI  - The value of belonging to organized dentistry.

PMID- 14685971
TI  - Pediatric dentistry--the hidden jewel of our profession.

PMID- 14685972
TI  - Oral and maxillofacial pathology case of the month. Canalicular adenoma.

PMID- 14685973
TI  - Automated external defibrillators can save lives.

PMID- 14685974
TI  - 20/20 is about perfect vision.

PMID- 14685975
TI  - Consider legal and business issues in management-service transactions.

PMID- 14685976
TI  - Dentistry and politics are not oil and water.

PMID- 14685977
TI  - Tooth-designation debate most famous of them all.

PMID- 14685978
TI  - Dynamics of a village--marketing strategies for a new millennium.
AB  - Successfully marketing a dental practice involves more than an ad in the yellow
      pages. Choosing a dentist is a decision based on emotion. Dentists who take steps
      to become involved in their communities and interact with people will reap the
      personal and professional rewards necessary for a successful practice. From the
      beginning of recorded time, humans have been strongly influenced by personal
      recommendations. It started in the Garden of Eden. Eve said to Adam, "Go ahead,
      taste this fruit." He didn't read about the fruit in a slick, full-color
      brochure. He didn't hear about it on television in a strategically placed
      commercial. He made his decision based on only one thing: Eve's recommendation.
      The power of a personal recommendation is still one of the strongest motivating
      factors in our society. People do not choose a good restaurant based on the size
      of its ad in the telephone directory. How many times have you told someone about
      a movie, and they saw it based on your recommendation? The synergy of human
      communication is the most powerful component of economic stability in a village.

PMID- 14685979
TI  - Making people want dentistry.
AB  - With advertisers spending millions of dollars for a share of consumers'
      disposable income, dentistry is up against fierce competition for patients.
      Dentistry will have to sell itself to keep up. One way to do this is to focus on
      the area in which consumers are increasing their spending--esthetics. Patients
      are drawn to a practice by appeals to their desire to look good. They can then be
      assessed for necessary work to improve their overall dental health.

PMID- 14685980
TI  - Diagnostic quiz #33. Case no. 1. Florid cemento-osseous dysplasia.

PMID- 14685981
TI  - Diagnostic quiz #33. Case no. 2. Chronic periodontitis.

PMID- 14685982
TI  - Diagnostic quiz #33. Case no. 3. Dentigerous cyst..

PMID- 14685983
TI  - 2001-2002 AANP national nurse practitioner practice site survey.
AB  - Between October 2001 and February 2002, AANP implemented the National NP Practice
      Site Survey. The purpose of the survey was to describe the general U.S. NP
      workforce, including the percentage of NPs working in primary care and their
      settings. Data were collected from over 39,000 NPs of all specialties. Based on
      the survey, a description of the U.S. NP Workforce was developed. For instance,
      according to the survey, the average NP is female (95%) and 47 years old. She has
      been in practice for 8.6 years, is a family NP (35%), and is involved in direct
      patient practice. This report includes detail on the respondents' clinical
      specialization, age, years of practice, and type of practice.

PMID- 14685984
TI  - Diagnosis and treatment of heel pain.
AB  - The American College of Foot and Ankle Surgeons (ACFAC) clinical practice
      guideline (CPG) summarizes the literature on the assessment and diagnosis of heel
      pain. The framework classifies heel pain depending on whether the cause is
      mechanical, neurological, arthritic, traumatic, or from another origin. Treatment
      strategies are included for the most common form of heel pain that are caused by
      mechanical problems.

PMID- 14685985
TI  - Sleep-disordered breathing in patients with heart failure: pathophysiology,
      assessment, and management.
AB  - PURPOSE: To provide clinicians in primary care settings information on the
      effects of sleep-disordered breathing in patients with heart failure (HF).
      Assessment and screening tools, as well as management considerations, are
      presented. DATA SOURCES: Review of the scientific literature of the past 10
      years, along with classic studies and Internet sources. CONCLUSIONS: HF is an
      increasingly prevalent problem with a high degree of associated sleep-disordered
      breathing. There are two broad categories of sleep-disordered breathing:
      obstructive sleep apnea and central sleep apnea/Cheyne-Stokes breathing. Both of
      these occur on a continuum of mild hypopnea to severe apnea with hypoxia. Sleep
      apneas are particularly harmful to patients with HF and, if left untreated, may
      adversely affect their prognosis. Yet sleep apnea is not routinely screened for
      in this population. IMPLICATIONS FOR PRACTICE: Given the serious consequences of
      untreated sleep-disordered breathing, there is sound justification to screen for
      sleep apnea in all patients with HF. Subsequent treatment of those patients with
      sleep apnea can significantly improve their quality of life and can decrease
      their mortality.

PMID- 14685986
TI  - The discovery of unique nurse practitioner theory in the literature: seeking
      evidence using an integrative review approach.
AB  - PURPOSE: To determine if theory unique to nurse practitioners (NPs) exists and to
      describe the attributes of such theory. DATA SOURCES: An integrative review of
      the literature was used. CINAHL and MEDLINE were searched using key terms such as
      nurse practitioners, theory, or research. Forty-five articles contributed to the
      final analysis. CONCLUSIONS: The NP role evolved from nursing yet is heavily
      influenced by medicine. This integration may affect both the use of theory in NP
      literature and the types of theories that are used to guide NP literature
      generation and research. Evidence was found of emerging theory unique to NPs with
      theoretical origins grounded in nursing, medicine, and social science.
      IMPLICATIONS FOR PRACTICE: NPs are beginning to develop theories of "nurse
      practitionering." This development is imperative for NP education, practice, and
      research to further the knowledge of the discipline and to help articulate the
      unique body of knowledge possessed by NPs.

PMID- 14685987
TI  - Nurse practitioner self-confidence and attitudes regarding managed care.
AB  - PURPOSE: To examine the relationship between nurse practitioner (NP) perceived
      self-confidence in performing managed care tasks and NP attitudes toward managed
      care. DATA SOURCES: A random sample of NPs--members of the Massachusetts
      Coalition of Nurse Practitioners--completed a demographic survey, responded to
      questions measuring self-confidence in performing managed care tasks and
      attitudes toward managed care, and wrote about their managed care experiences.
      CONCLUSIONS: NPs were only moderately confident in performing managed care tasks
      and had mostly negative attitudes toward managed care. They reported intense
      frustration related to prescriptive coverage and referrals to specialty services,
      potential trust issues between providers and patients, and ethical and legal
      dilemmas in tailoring plans of care to fit the patient's insurance. The NPs'
      written comments indicate a need for more in-depth exploration of NP attitudes
      toward managed care. IMPLICATIONS FOR PRACTICE AND EDUCATION: Continuing
      education in selected managed care competencies, better education of NP students,
      and promotion of organizational cultures that support interdisciplinary teamwork
      as well as population- and evidence-based practice may help NPs to embrace the
      promise of managed care and to offer solutions to its problems.

PMID- 14685988
TI  - Knowledge of AIDS, perceived risk of AIDS, and at-risk sexual behaviors among
      older adults.
AB  - PURPOSE: To identify older adults' knowledge of acquired immune deficiency
      syndrome (AIDS), perceptions of their risk of AIDS, and at-risk behaviors by
      using a questionnaire derived from the health belief model. DATA SOURCES: A
      descriptive correlation design was used to survey persons 50 years of age and
      older who participate in university-based senior programs. The sample of 166
      persons (55% return rate) had a mean age of 71 years and included 33% males. The
      sample is representative of the participants in these programs. CONCLUSIONS: Five
      hypotheses based on the health belief model were tested. Statistical analyses
      showed significant predictors of the likelihood of using recommended safe sexual
      practices were gender, knowledge of AIDS, perceived susceptibility to AIDS, and
      perceived threat of AIDS. The results indicated the respondents were
      knowledgeable about human immunodeficiency virus (HIV) transmission through
      casual contact and medical aspects of AIDS. Although the respondents recognized
      the seriousness of AIDS, they generally did not believe that they were
      susceptible to this disease, even though about 10% indicated sexual activity
      outside of a long-term relationship. IMPLICATIONS FOR PRACTICE: The study
      findings support the need for nurse practitioners to assess sexual behaviors in
      and provide information about safe sex practices to older clients because of the
      documented rising incidence of AIDS in persons over 50 years of age.

PMID- 14685989
TI  - Improving access--an innovative model.
AB  - PURPOSE: To present a model of health care delivery in South Africa that made
      health care services accessible and affordable to members of the community who do
      not have medical insurance. DATA SOURCES: Statutes and laws governing the
      practice of health care professionals in South Africa, published professional
      guidelines, local research data, and the author's experience of the model of
      health care delivery. CONCLUSIONS: The innovative and visionary approach of a few
      health care professionals has established a model of health care delivery
      specifically suited to their community's needs. This model of service delivery
      has provided an affordable and accessible health service to members of the local
      community, who have indicated their satisfaction with the service. IMPLICATIONS
      FOR PRACTICE: Economic and legal barriers to accessible and affordable health
      care services can be overcome to ensure that health care is available to the
      whole population. The nurse practitioner has an important role to play in making
      health care affordable and accessible to the community.

PMID- 14685990
TI  - Ethics in action. Avoiding the power play.

PMID- 14685995
TI  - When the liver fails: new help--and hope.

PMID- 14685996
TI  - Shining the light on benefits.

PMID- 14685997
TI  - What's wrong with this patient? POEMS syndrome.

PMID- 14685998
TI  - Women's health. Osteoporosis.

PMID- 14685999
TI  - Incident reports are a must.

PMID- 14686000
TI  - The employment-related breastfeeding decisions of physician mothers.
AB  - One hundred and forty-six physician mothers responded to a survey of their
      personal decisions regarding employment and breastfeeding. The mean duration of
      breastfeeding was 18.8 weeks with a range of 1 week to 128 weeks. The three major
      factors contributed to the physician mother' decisions to completely wean their
      children were return to work (45%), diminishing milk supply (31%), and lack of
      time to pump (18%). Return to part-time work was positively associated with
      greater duration of maternity leave and breastfeeding. The relationship between
      breastfeeding and weeks of maternity leave was positive for first- and second
      born children. It was not significant for subsequent children. Upon returning to
      work, space and time for milk expression were obstacles for the majority of the
      physician mothers. Without time, space, and workplace support, mothers who
      attempt to combine full time employment and breastfeeding are likely to delay or
      skip milk expression. This may cause them to experience breastfeeding problems,
      resulting in premature weaning. Flexible employment arrangements may increase
      duration among physician mothers and provide an atmosphere of greater acceptance.
      Protected time and a space for milk expression could contribute to greater
      frequency of pumping and fewer problems associated with incomplete emptying of
      the breast.

PMID- 14686001
TI  - Our children's obesity epidemic: can MSMA help legislatively mandate a cure?
      What's your opinion, doctor?

PMID- 14686002
TI  - Best form of prevention: health education in the schools.

PMID- 14686003
TI  - Looking back: transfusion in 1916.

PMID- 14686004
TI  - [Frequency of congenital abnormalities in Hungary after the Chernobyl nuclear
      power accident].
AB  - INTRODUCTION: The only positive result of earlier Hungarian teratological
      investigations on consequences of Chernobyl nuclear power station accident was
      the description of increased prevalence of birth with less than 2500 g body
      weight. It was attributed to the concern of the pregnant women, not to the direct
      effect of ionising radiation. AIM: The present study aimed to refine the earlier
      results by application of sensitive epidemiological techniques. METHOD: The
      exposure data observed in the 150 districts of Hungary were correlated with the
      prevalence of Down syndrome by geographical information system and the monthly
      detected prevalences were analysed in the function of exposure. RESULTS: The
      ecological investigation on geographical inequalities revealed that there is no
      correlation between the district level exposure and Down syndrome prevalence. The
      time trend analysis on monthly data showed no exposure-related elevation of Down
      syndrome occurrence. CONCLUSION: The results supported the earlier conclusions of
      the studies that the Chernobyl accident related exposure did not elicited
      detectable increase of Down syndrome.

PMID- 14686005
TI  - [Effect of imatinib treatment of gastrointestinal stromal tumors].
AB  - INTRODUCTION: Advanced malignant gastrointestinal stromal tumours are practically
      resistant to further radio- or chemotherapy. These tumours are characterized by
      the presence of C-KIT (a transmembrane tyrosin kinase) mutation which can be
      specified by CD117 expression. Imatinib (2-fenilaminopirimidine) is a selective
      inhibitor of the mutated C-KIT. AIM: The purpose of our study was to determine
      the potential antitumour effect of imatinib in patients with gastrointestinal
      stroma tumour patients. MATERIALS AND METHODS: An open, non-randomized trial was
      performed involving 38 patients each of which had received/metastatic disease
      associated with CD117 positivity. Consecutively daily doses of 400-600 mg
      imatinib was administered orally to the patients. The evaluation was carried out
      on 37 patients in a form of an interim analysis. RESULTS: After a 3-18 months
      observation period 1 complete, 19 partial remissions and 10 static diseases could
      be registered (78%), in association of only grade 1-2 toxicity. CONCLUSIONS: The
      imatinib treatment improved the quality of life of the patients with
      gastrointestinal stroma tumour and their life expectancy became considerably
      prolonged. Further follow-up of the patients as well as design of a prospective,
      randomized trial on a larger patient material is urgently needed.

PMID- 14686006
TI  - [Plasmapheresis therapy in systemic sclerosis].
AB  - BACKGROUND: Systemic sclerosis (SSc) is a polysystemic autoimmune disorder
      characterized by excessive production of extracellular matrix and vascular
      abnormalities, involving the skin and internal organs. There is currently no real
      disease-modifying therapy of SSc and there are only few reports on the use of
      plasmapheresis in SSc. OBJECTIVES: Authors present 4 cases of SSc treated with
      plasmapheresis within one year from disease onset. All patients had diffuse
      cutaneous form of SSc with rapid progression and with different internal organ
      manifestations. METHODS: The patients were treated with plasmapheresis performed
      every 3 months besides symptomatic drug treatment. Clinical symptoms, Rodnan skin
      score, immunolaboratory markers (serum immunoglobulin, complement, several
      autoantibodies, leukocyte CD markers) and soluble adhesion molecules (E-selectin,
      intercellular adhesion molecule 1, vascular cell adhesion molecule, which were
      showed as the markers of disease activity in previous works) were determined
      before and after the plasmapheresis. RESULTS: The progression of the disease
      slowed down significantly in all patients, no more new clinical manifestation
      appeared, Rodnan skin score significantly decreased. There was a reduction in
      CD4/CD8 ratio (approaching normal ratio), in expression of CD69, as early
      activation marker. There was a significant suppression of soluble adhesion
      molecules also in all patients. CONCLUSION: In patients with diffuse cutaneous
      form of SSc, plasmapheresis may be effective with decreasing progression of the
      disease and improving clinical symptoms (especially skin manifestation) in the
      early phase of the disease.

PMID- 14686007
TI  - [The role of oxidative stress and arterial blood supply in the transplanted liver
      function].
AB  - INTRODUCTION: Reperfusion injury and hepatic artery thrombosis are major causes
      of graft failure after liver transplantation. The magnitude of oxidative stress
      increases after reperfusion and the appearance of an arterial thrombosis presents
      a higher risk for the graft and patient survival. AIM OF THE STUDY: The aim of
      the study was to detect the level of oxidative stress in the perioperative period
      of transplantation. METHODS: Clinical documentations of 32 patients were
      investigated and the level of myeloperoxidase (MPO) was measured for the
      monitoring of the oxidative stress. RESULTS: The mean age of the patients was 43
      years and hepatitis C cirrhosis was the most common indication (14 cases, 43%).
      Two retransplantations were done. In 24 cases (75%) the primary graft functions
      and patient survival were good. Eight patients died, in two cases because of
      acute liver failure, in two cases due to primary non function and in four cases
      due to late complications. The incidence of hepatic artery thrombosis was 11% (4
      cases) and the incidence of acute rejection was 35% (12 cases). The level of MPO
      was higher (65 ng/ml) in all patients before operation. After the first 48 hours
      this level increased significantly (p < 0.0001) up to the mean level of 123 ng/ml
      and decreased after one week. In the cases with acute liver failure and hepatic
      artery thrombosis high levels of MPO were measured. CONCLUSION: This study
      provides evidence of increased oxidative stress before liver transplantation. The
      magnitude of these changes increased after operation, mostly in cases with acute
      liver failure and hepatic artery thrombosis. Reducing the reperfusion injury and
      performing an "ideal" arterial supply for the liver-graft present better
      survival.

PMID- 14686008
TI  - [Frequency of anemia in patients with ovarian cancer: assessment of our own data
      in connection with the European Cancer Anemia Survey (ECAS)].
AB  - The authors summarized the hemoglobin values of 174 patients in 850 chemotherapy
      courses with ovarian cancer in the year 2001 on the base of the European Cancer
      Anemia Survey's results. Chemotherapy was given in first-line in 88, in second-in
      68 and in third- and fourth-line in 16 and 2 patients. Patients were divided into
      2 treatment (cisplatin and non-cisplatin) groups according to the different
      anemia-producing characteristics. The average Hb levels in the two groups were as
      11.1 g% and 11.2 g%, and the median Hb values were as 11.2 g% and 11.7 g%,
      respectively (p = 0.3604). The Hb values were lower than the normal Hb limits (G1
      4) in 70.5% and in 61.8% in the two groups. There was not found significant
      difference between the two treatment arms in the G3-4 toxicity (2.9%, 1.1%, p =
      0.8572). Data of the authors underline the importance of prophylaxis and
      treatment of anemia in chemotherapy courses of ovarian cancer patients.

PMID- 14686009
TI  - [Treatment of benign prostatic hypertrophy].

PMID- 14686010
TI  - [The role of Doctors Vilmos Zlamal, Sr. and Jr., in the development of veterinary
      and human medicine in Hungary].

PMID- 14686011
TI  - ECG acquisition using telemedicine in Alaska.
AB  - The Alaska Federal Health Care Access Network includes a telecommunications
      network supporting telemedicine carts and store-and-forward telemedicine software
      throughout Alaska. Electrocardiograms are being acquired at remote locations and
      being interpreted at regional and tertiary care facilities as part of routine and
      acute care. This promising new technology is just beginning to have an impact on
      cardiovascular patient care.

PMID- 14686012
TI  - Pediatrics in the Panhandle.

PMID- 14686013
TI  - The Open Door Clinic.

PMID- 14686014
TI  - Fairview Family Service Center.

PMID- 14686015
TI  - Uterine contraction frequency before and after successful tocolytic therapy for
      preterm uterine contractions.
AB  - OBJECTIVE: To examine the association between prelabor uterine contraction
      frequency (UCF) and the success of tocolytic therapy for preterm labor (PTL).
      STUDY DESIGN: Eleven centers conducted a prospective, observational study of UCF
      recorded between 22(0/7) and 36(6/7) weeks' gestational age or until delivery >
      or = 2 times/d on > or = 2 d/wk in women with singleton pregnancies with and
      without risk factors for preterm birth. Uterine contraction data obtained from
      patients diagnosed with PTL allowed comparison of mean UCF both before and after
      an acute episode of PTL treated with either intravenous, subcutaneous or oral
      tocolysis. The signed rank test was used to analyze differences in UCF before and
      after tocolytic therapy and between women who were or were not successfully
      treated with a labor-inhibiting agent. RESULTS: Of 454 enrolled women, 128 were
      diagnosed with PTL, and 74 were successfully treated with a labor-inhibiting
      agent. The mean UCF preceding PTL was not different between those women
      successfully treated and those who delivered as a consequence of the PTL episode.
      There was no difference (P = .653) in mean UCF between the week before PTL (UCF
      0.60 +/- 0.8, median 0.30) and the first week of monitoring after successful
      tocolysis (UCF 0.82 +/- 1.4, median 0.27). CONCLUSION: The mean UCF immediately
      preceding PTL does not predict tocolytic success or failure.

PMID- 14686016
TI  - Teaching operative dictation. A survey of obstetrics/gynecology residency program
      directors.
AB  - OBJECTIVE: To assess current efforts to teach operative dictation in obstetrics
      and gynecology residency programs. STUDY DESIGN: A survey detailing the didactics
      of operative dictation was distributed in a single mailing to all program
      directors listed in the roster of the Council on Residency Education in
      Obstetrics and Gynecology. RESULTS: Of 274 surveys distributed, 115 (42%) were
      returned. Ten percent of program directors reported defined curricula related to
      operative dictation. Using a combination of lectures, personal instruction and
      review of previous notes, attendings and senior residents share the
      responsibility for teaching operative dictation in the majority (78%) of
      programs. Sixty percent of program directors were in favor of more formal
      guidelines for residency education in the technique of operative dictation, 34%
      were opposed, and 6% offered no opinion. CONCLUSION: Obstetrics and gynecology
      residency programs rarely have a structured curriculum for teaching operative
      dictation, and the majority of program directors support the institution of more
      formal guidelines.

PMID- 14686017
TI  - Value of routine urine culture in the assessment of preterm labor.
AB  - OBJECTIVE: To assess the utility and expense of routine urine culture in women
      evaluated for preterm labor. STUDY DESIGN: A retrospective study of 1,429
      patients evaluated for preterm labor over a calendar year. Patients evaluated for
      preterm labor were identified using the hospital's admissions database and then
      cross-referenced with the hospital microbiology laboratory's database to identify
      those who had urine cultures sent as part of their evaluation. The charts of
      patients with a positive urine culture were further reviewed to evaluate the
      diagnosis and outcome. RESULTS: Five hundred twelve urine cultures were sent for
      analysis of preterm labor, and 6 (1.2%) reported growth of > 100,000 colonies of
      a single bacterium. Of these 6 patients, 5 reported symptoms consistent with a
      urinary tract infection, while the 6th was asymptomatic. Fisher's exact test
      showed no clinical significance for a positive urine culture as a predictor of
      preterm delivery (P = .68). Sensitivity was 0.7% (95% CI, 0.0-4.3), and
      specificity was 98.6% (95% CI, 96.7-99.5). A cost difference of $29,676 existed
      between charges and reimbursements. A positive culture was not a significant risk
      factor for preterm delivery. The 1 patient who delivered preterm with a positive
      culture probably had cervical incompetence as the cause of preterm delivery.
      CONCLUSION: The routine use of urine cultures in the assessment of preterm labor
      is costly and adds little value to obtaining a diagnosis except in the presence
      of specific complaints at our institution. Urine culture identified a single
      patient with asymptomatic bacteriuria being evaluated for preterm labor, and she
      probably had another etiology for her advanced cervical examination.

PMID- 14686018
TI  - Generalized vulvar dysesthesia vs. vestibulodynia. Are they distinct diagnoses?
AB  - OBJECTIVE: To evaluate prospectively whether generalized vulvar dysesthesia and
      vestibulodynia possess unique characteristics that support the theory of
      differing etiologies. STUDY DESIGN: Women with vulvar dysesthesia for a minimum
      of 3 months were enrolled at the University of Michigan in 2 clinics specializing
      in vulvar disorders. Informed consent was obtained. Participants completed a 27
      page questionnaire and had a physical examination. Differentiation of generalized
      vulvar dysesthesia and vestibulodynia was based on tenderness to light pressure
      isolated to the introitus vs. pain beyond the introitus, respectively. We
      compared women with the 2 diagnoses to each other on demographic characteristics,
      exposures, pain characteristics and physical findings using t test, Mann-Whitney
      U and chi 2 analysis. RESULTS: Between January 26, 2001, and August 28, 2002, we
      enrolled 39 women, aged 18-60 years, with tenderness localized to the vestibule
      (vestibulodynia) and 17 with generalized vulvar dysesthesia. Women in each
      diagnostic group were similar in demographic and exposure characteristics. The
      pain characteristics were similar between the 2 groups except that recent pain
      was rated as worse by those with generalized vulvar dysesthesia. Activities that
      aggravated or relieved the pain were similar. However, women with generalized
      vulvar dysesthesia were more likely to state that their pain was aggravated by
      sitting and by washing the area. Similar results were found when using
      "continuous" pain rather than vulvar pain location as the outcome variable.
      CONCLUSION: The characteristics of women with generalized vulvar dysesthesia are
      similar to those with localized pain, supporting the theory that the 2 disorders
      may exhibit 2 presentations on a continuum of severity seen in vulvar dysesthesia
      rather than 2 distinct entities.

PMID- 14686019
TI  - Using a vortex mixer for testicular sperm collection.
AB  - OBJECTIVE: To evaluate 2 methods of processing testicular tissue for the
      retrieval of viable sperm from men with nonobstructive azoospermia. STUDY DESIGN:
      Fresh testicular tissue was obtained from nonobstructive azoospermia patients
      using a biopsy needle. The specimens were divided into 2 fractions. All specimens
      were minced and immersed in human tubal fluid (HTF). The first fraction was
      filtered through a nylon filter and incubated for 3 hours. The supernatant was
      centrifuged, resuspended in HTF and analyzed. The second fraction was immediately
      vortexed for 5 minutes and filtered through a nylon filter. The supernatant was
      centrifuged, resuspended in HTF and analyzed. RESULTS: Spermatozoa were obtained
      in 13 of 24 cases (54.2%) using the vortex method and in 5 of 24 cases (20.8%)
      with the nylon filter method. CONCLUSION: The vortex mixing method may be a
      better option than the conventional method for processing testicular tissue for
      sperm collection.

PMID- 14686020
TI  - Outpatient implantation of a central venous access system in gynecologic oncology
      patients.
AB  - OBJECTIVE: To determine the feasibility, accuracy, complications and cost of
      implantation of the PORT-A-CATH II Fluoro-Free venous access system (SIMS Deltec
      Inc., St. Paul, Minnesota) in the procedure room setting. STUDY DESIGN: A
      prospective study of 49 consecutive gynecologic oncology patients who underwent
      53 PORT-A-CATH II System implantations was conducted. Local anesthesia and
      conscious sedation were used for the procedure. To localize and position the
      catheter tip, the CATH-FINDER (SIMS Deltec) electronic catheter sensing device
      was utilized. Demographic characteristics, operative data, complication rates,
      failure rates and itemized costs were collected and analyzed. RESULTS: For the 53
      ports implanted, the mean operative time was 54 minutes (range, 39-74) and mean
      estimated blood loss was 17 mL (range, 7-50). Immediate complications included
      failure to thread the catheter or guidewire past the left subclavian vein (4
      patients), pneumothorax (1) and electronic wire fracture (1). All catheter tips
      were positioned accurately, as confirmed by chest radiography. The procedural
      charge ranged from $1,946 to $2,042. The CATH-FINDER obviated the need for, and
      expenses of, fluoroscopy, operating room and anesthesia services, resulting in
      savings of approximately $2,000 per procedure. CONCLUSION: Implantation of the
      PORT-A-CATH II System was performed safely, accurately and cost effectively in
      the procedure room setting. The advantages of functional longevity, low
      complication rates and reduced cost of this port system offer an excellent option
      for long-term central venous access.

PMID- 14686021
TI  - Thin-layer cytology and histopathology in the evaluation of abnormal uterine
      bleeding.
AB  - OBJECTIVE: To compare thin-layer endometrial cytology to endometrial biopsy and
      surgical pathology in women with abnormal uterine bleeding. STUDY DESIGN: We
      performed a prospective study of 103 women. Patients underwent endometrial
      cytologic evaluation using an endometrial brush, followed by either endometrial
      biopsy, hysteroscopy with dilation and curettage, or hysterectomy, as clinically
      indicated. Test performance characteristics and adequacy of cytology and
      endometrial biopsy were assessed. Ki-67 immunocytochemical expression was
      evaluated in a random subset of 60 specimens. RESULTS: Cytologic sampling
      demonstrated a sensitivity of 78%, a specificity of 96%, a positive predictive
      value of 78% and a negative predictive value of 96% for the detection of
      endometrial abnormalities. The unsatisfactory rate of uterine cytology was 15% as
      compared to 26% for endometrial biopsy. Of adenocarcinoma cases, 83% expressed Ki
      67, as compared to 30% in benign cases. CONCLUSION: Endometrial cytology may be
      useful in the detection of endometrial hyperplasia and neoplasia and provides
      adequate material for the assessment of Ki-67.

PMID- 14686022
TI  - Rectovaginal injury in a young child. A case report.
AB  - BACKGROUND: Rectovaginal injuries in children, often the result of trauma,
      present as emergencies. Associated injuries may include ruptured urethra,
      bladder, vaginal vault or hollow viscus. CASE: A child younger than 2 years of
      age sustained a traumatic injury. Thorough examination required the use of
      skeletal radiography; computed tomography of the head, chest, abdomen and pelvis;
      and voiding cystourethrogram. Injury was limited to a fourth-degree perineal
      laceration. The wound was debrided and primarily closed in layered fashion. A
      diverting colostomy was performed to aid wound healing. Six weeks later, after
      wound resolution, colonic anastomosis was performed. CONCLUSION: Rectovaginal
      laceration in a child under the age of 13 requires thorough evaluation to
      identify the extent of traumatic injury. A diverting colostomy enhances wound
      healing.

PMID- 14686023
TI  - Use of a subcutaneous beta-sympathomimetic pump for the treatment of fetal
      congenital complete heart block. A case report.
AB  - BACKGROUND: Complete heart block is the most common congenital heart block
      diagnosed in the fetalneonatal period. Maternal administration of beta
      sympathomimetic agents has been used to treat this condition in the fetus. We
      know of no previous reports of the delivery of beta-sympathomimetics via a
      continuous subcutaneous pump for management of this condition. CASE: An
      intrauterine gestation at 28 5/7 weeks complicated by fetal congenital complete
      heart block was successfully managed to term with maternal administration of a
      beta-sympathomimetic agent via a continuous subcutaneous pump. CONCLUSION:
      Maternal administration of beta-sympathomimetic agents by a continuous
      subcutaneous pump in cases of fetal congenital complete heart block may help
      prolong pregnancy by preventing hydrops fetalis and avoiding confounding problems
      of prematurity. However, it should be used with caution due to the potential for
      dilated cardiomyopathy in the infant.

PMID- 14686024
TI  - Emphysema of the abdominal wall obscuring postcesarean volvulus. A case report.
AB  - BACKGROUND: Emphysema of the abdominal wall occurs after infection with gas
      forming organisms or when intraabdominal gas has a mechanical pathway to the
      retroperitoneum. CASE: Emphysema of the abdominal wall associated with volvulus
      developed after cesarean delivery. CONCLUSION: Postcesarean abdominal pathology
      may be associated with emphysema of the abdominal wall.

PMID- 14686025
TI  - Primary malignant lymphoma of the cervix. A case report.
AB  - BACKGROUND: Primary malignant lymphoma of the female genital tract is rare. A
      review of the literature suggests that 1 in 175 extranodal lymphomas in women is
      likely to originate in the vagina, uterus or cervix. Often the diagnosis of
      primary lymphoma is not established until after an operation has been performed.
      Postsurgical treatment is usually chemotherapy alone or followed by radiotherapy.
      CASE: A 40-year-old woman presented in January 2001 with uterine bleeding. After
      the patient underwent total abdominal hysterectomy, primary cervical malignant
      lymphoma was diagnosed. Six courses of chemotherapy were administered in an
      adjuvant setting. Twenty-seven months (April 2003) after the diagnosis the
      patient was alive and without signs of recurrent disease. CONCLUSION: Awareness
      of this rare clinical entity is important because these tumors can present at any
      age and may mimic squamous cell carcinoma of the cervix clinically and
      histologically. Abnormal uterine bleeding is the most common presenting symptom
      of primary malignant lymphoma of the cervix. Extent of disease, size of primary
      lesion and type of lymphoma are significant prognostic features. Radical surgery
      is unnecessary. Standard postsurgical treatment has not yet been established.

PMID- 14686026
TI  - Mayer-Rokitansky-Kuster-Hauser syndrome associated with unilateral gonadal
      agenesis. A case report.
AB  - BACKGROUND: Mayer-Rokitansky-Kuster-Hauser syndrome is the second most frequent
      cause of primary amenorrhea, with a reported incidence of 0.002%. Patients have a
      normal karyo-type and usually normal ovaries. Associated ovarian abnormalities
      are rarely reported. CASE: A 17-year-old woman with primary amenorrhea was
      evaluated by diagnostic laparoscopy, which showed complete mullerian agenesis. On
      the left side, the uterine tube and round ligament were hypoplastic, and the
      ovary was absent. The karyotype was 46, XX. Intravenous urography revealed a
      right kidney below the normal site with malrotation abnormality. CONCLUSION:
      Mullerian duct agenesis coexisting with unilateral ovarian agenesis and a
      contralateral renal abnormality has not been widely described before.
      Unilaterality might play a role in the etiologic factor of Mayer-Rokitansky
      Kuster-Hauser syndrome.

PMID- 14686027
TI  - Treating a recurrent uterine arteriovenous malformation with uterine artery
      embolization. A case report.
AB  - BACKGROUND: Uterine arteriovenous malformation is a rare condition. Uterine
      artery embolization offers the possibility of conservative management as opposed
      to the traditional hysterectomy. We report a case with recurrent uterine
      arteriovenous malformation confirmed by angiography and successfully treated with
      a second embolization procedure. CASE: A 33-year-old woman presented with heavy
      vaginal bleeding. The diagnosis of uterine arteriovenous malformation was
      suspected on Doppler ultrasonography and confirmed by angiography. The first
      embolization procedure was performed using polyvinyl alcohol and steel coils.
      Recurrence was diagnosed 1 year later with the same imaging techniques. The
      second embolization procedure was performed using histoacryl. The patient
      remained asymptomatic at 1-year of follow-up. CONCLUSION: Minimally invasive
      management is an option in recurrent uterine arteriovenous malformation.

PMID- 14686028
TI  - Venous thromboembolism. A review.
AB  - Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary
      embolism (PE). A number of factors can increase VTE risk, including aging,
      smoking, immobility, pregnancy and a hereditary thrombophilia. Presenting
      symptoms are not definitive for DVT or PE, and objective testing is necessary for
      an accurate diagnosis. A number of antithrombolic agents are used in the
      prophylaxis and treatment of VTE. The current trend is toward using low-molecular
      weight heparins instead of unfractionated heparin. There is increasing interest
      in new agents that can target a single factor in the coagulation cascade.

PMID- 14686029
TI  - Venous thromboembolism in the pregnant woman.
AB  - The incidence of venous thromboembolism (vein thrombosis [DVT] and pulmonary
      embolism [PE]) increases sharply in pregnant women. The 3 primary contributing
      factors in VTE--hypercoagulability, stasis and endothelial injury--can all occur
      in association with pregnancy. Symptoms that may suggest VTE are often inherent
      in pregnancy, such as leg pain and shortness of breath, making clinical diagnosis
      problematic. The use of objective diagnostic testing for VTE is complicated in
      pregnancy because many of the tests commonly used present a potential risk to the
      fetus. Heparin does not cross the placenta and is not teratogenic, making it the
      first-line treatment for VTE. Low-molecular-weight heparins are typically the
      drug of choice for prophylaxis and treatment of VTE in pregnant women.

PMID- 14686030
TI  - The truth about oral contraceptives and venous thromboembolism.
AB  - In the last decade, the contribution of the progestin component of oral
      contraceptives (OCs) to the risk of venous thromboembolism (VTE) has come under
      scrutiny. The publication of 4 papers in late 1995 and early 1996 led to many
      women discontinuing OCs containing desogestrel and gastodene, the so-called third
      generation OCs. This "pill scare" was the result of study findings that the third
      generation OCs were associated with a higher risk of VTE than were OCs containing
      older progestins, primarily levonorgestrel. Subsequent studies and reanalysis of
      the original studies have not provided a definitive answer to this continuing
      debate. More recently, a question was raised about a possible increase in the
      risk of VTE associated with the use of an OC containing the novel progestin
      drospirenone. However, the information to date does not support any increase in
      the risk of VTE with use of the drospirenone-containing OC as compared with any
      other combination OC.

PMID- 14686031
TI  - What counts. Facts, figures, findings.

PMID- 14686032
TI  - More than we can chew. Health care system choking on its own complexity.

PMID- 14686033
TI  - New HIPAA transaction regulations now in effect.

PMID- 14686034
TI  - Be a smart shopper. Technology budget planning.

PMID- 14686035
TI  - Consider it job security. Creating an effective physician-administrator team.

PMID- 14686036
TI  - Live and learn. Fellowships, internships prepare the medical practice managers of
      tomorrow.

PMID- 14686037
TI  - Art and community. Reaching out from the family practice office.

PMID- 14686038
TI  - Code road. Case study: developing a coding department.

PMID- 14686039
TI  - How am I doing, coach? A mentor can help you develop your potential.
AB  - Mentoring. Coaching. It's all in a day's work for a busy medical practice
      executive. But many managers in medium-and smaller-sized medical groups find that
      being the practice's "go-to" person is a lonely job.

PMID- 14686040
TI  - An exercise in controversy. Case study: revising a physician employment
      agreement.
AB  - The physician employment agreement at a faculty practice plan did not meet the
      needs of a modern health care employer or its medical staff. This article
      describes the communication among medical group management, medical leadership
      and the medical staff during the revision of the agreement, as well as the
      process used to develop a new document.

PMID- 14686041
TI  - Steer clear. Medical group, hospital physician-recruiting violations can have
      dire consequences.
AB  - Hospitals and medical groups can and often do make amicable partners in physician
      recruiting. However, violating the rules of such partnerships can have serious
      ramifications for the group, the hospital and newly recruited physicians.

PMID- 14686042
TI  - On board or bored stiff? How to run effective board meetings.
AB  - Boards of directors meet to resolve problems or make decisions. To get the most
      out of your practice's board meetings, know when and why you need to meet, who
      needs to attend, how to run the meeting effectively and whom you represent.

PMID- 14686043
TI  - [Alternative/complementary treatments: knowledge and practice of nurses in the
      71st administrative district --Santo Amaro-Sao Paulo].
AB  - The purpose of this study is to investigate the nurses knowledge and actions
      taken regarding alternative or complementary therapies (AT or CT) at the County
      (municipal) Health Units of the 71st Administrative District, in Santo Amaro, SP.
      The research use a quantitative apProach and a qualitative analysis of the field
      data that showed that 89% of the nurses have confidence in AT/CTs but only 22.2%
      know the legal basis for its use and 5.5% had courses on the techniques. 44.4%
      use these therapies on themselves and 11.1% on their patients. Altogether 7
      different AT/CTs were listed and classified in 5 Hill's groups. It was found that
      there is a need for including new knowledge as a complementary option for the
      promotion of the population's health.

PMID- 14686044
TI  - [Descentralization as a guiding principle in the reorganization and
      implementation of the principles of the Unified Health System].
AB  - The organization of the health sector in Brazil changed significantly after the
      ratification of the Federal Constitution in 1988 and the Organic Health Laws in
      1990. Decentralization of health services has been the basis for the
      implementation of the organizational and management principles in the Brazilian
      Unified Health System. This study presents some of the experiences in the health
      sector that have contributed decisively to the development of such principles,
      caused important changes in the present care model, and achieved significant
      results in social health production.

PMID- 14686045
TI  - [Dialectic of the daily life of patients with chronic kidney failure: the
      unavoidable and the casual].
AB  - The objective of this study was to understand the social reality of patients'
      daily life with chronic renal failure in hemodialysis. To understand this
      phenomenon from the theoretical-methodological referential of the historic and
      dialectic materialism. The interviews were performed with 18 patients submitted
      to analysis of speech procedure revealing dialectics subjects. These subjects
      were analyzed regarding the categories: health-disease process; possibility x
      reality and need x casualness. These patients, considered hemodialysis as a
      treatment unavoidable and the transplant casual, thus, between this dialectic
      relationship there is the nursing which needs to extend its comprehension on thr
      arduous, sad, difficult and monotonous reality and the possibilities o
      transformation.

PMID- 14686046
TI  - [Experience of nursing education in collective health: informatics used to teach
      epidemiologic surveillance].
AB  - This article discusses the application of information technology (IT) in
      education, its benefits and the ethical and ideological implications in using
      this tool in nursing education and work. It relates the experience of developing
      contents on epidemiological surveillance. Some pedagogical experiences were given
      to the students handling an Aids database, with the purpose of motivating them to
      express their understanding and to reflect on the health problems of the
      population, associating the occurrence and the profiles of this epidemic in
      different areas of the city of Sao Paulo, with the forms of work and life of
      population groups in certain places. The understanding of the health-disease
      process was enlarged. IT is a potent instrument in epidemiological surveillance
      for the teacher who act as mediator between the information and the knowledge
      that one wants to build.

PMID- 14686047
TI  - [Development of an on-line course on medication administration].
AB  - The study describes the development of an on-line course on medication
      administration. The World Wide Web Course Tools (WebCT) that was used is software
      that provides various tools for supervisors and access to a number of
      environments for students who have a password. The course material is presented
      in a series of websites which are sub-divided into eight illustrated topics
      concerning medication administration routes, in addition to questions for
      knowledge assessment. A sample of undergraduate students at the University of Sao
      Paulo at Ribeirao Preto College of Nursing has positively evaluated the course.
      It is now intended to be included as curricular course in the undergraduate
      program as an additional resource for student learning.

PMID- 14686048
TI  - [Anxiety and coping mechanisms used by ambulatory surgery patients].
AB  - The goals of this study were to identify the anxiety state in surgical ambulatory
      patients in the pre-operative period, the coping mechanisms employed, their
      clinical manifestation, and to verify the influence of state anxiety during the
      pre-operative period. The results showed that 40 patients exhibited little
      anxiety and there was no significantly statistical correlation between
      preoperative anxiety state, coping mechanisms and clinical changes.

PMID- 14686049
TI  - [Stress in nursing work].
AB  - The aim of this study was to appraise stress levels of nurses working with
      mentally ill psychiatric hospital patients. This quantitative study was conducted
      in seven psychiatric hospitals in the city of Fortaleza, Ceara, Brazil, and was
      carried out with the use of the following instruments: Socio-demographic
      descriptive information of the sample and an inventory to identify the stress
      symptoms of the nurses. The sample size was 48, of which 42 (92.9%) were female.
      The results of the sample showed that 62% felt no stress, 30.9% were at the
      endurance level and 7% at the exhaustion level. No statistically significant
      relationship was found between the hours of work performed and the symptoms of
      stress. Therefore, the present study showed no occurrence of stress in these
      nurses.

PMID- 14686050
TI  - [The dimensions of care at a burn unit: ethnographic study].
AB  - This aim of this ethnographic study is to understand a nursing staff's cultural
      perspectives throughout the care of a burned client in a burn unit. Data were
      collected through observation and interviews and interpreted in accordance with
      Bourdieu's perspective, that uses the habitus concepts and field to understand
      the behaviors that express what is internalized by people that belong to a social
      group. To carry out these dimensions of care, the professionals act in agreement
      with the forms that already internalized, and they expressed in their
      depositions: to suffer together, to act firmly, and at the same time, to be kind
      and affectionate.

PMID- 14686051
TI  - [Sexuality as cultural construction: reflections on inherent prejudice and myths
      in a group of rural women].
AB  - The present work focuses on sexuality as a cultural construct. To support this
      idea, a study was carried out with a group of eleven women from a rural
      community, in the countryside of Rio Grande do Sul, Brazil. The data was
      collected through semi-structured interviews and the narratives were analyzed
      qualitatively, seeking to extract meaning from the inquiries by viewing them
      through a cultural lens. Sexuality is viewed as a personal experience, composed
      of values, beliefs, myths and prejudice assimilated during the socialization of
      each respondent. Reflections highlighting the importance of cultural
      interpretation of the events for nurses, especially those referring to sexuality
      to the nurses, were included.

PMID- 14686052
TI  - [Smear test from the point of view of women who undergo it].
AB  - This research is the result of my experience with women in cervical cancer
      prevention at the Gynecology and Obstetrics National Health Clinic of the Federal
      University of Minas Gerais. I tried to understand what it means to women who are
      submitted to a smear test. To achieve this, I have used a qualitative research,
      in a phenomenological approach. I gathered the data from interviews about the
      main subject. The analysis of those eleven interviews have helped me to build
      three analytical categories that are the located structure of the phenomenon, as
      follows: A--The preventive cervical cancer examination: a woman as a human being
      conscious of the world; B--Facing the smear test: manifestation of the existence;
      C--Working with the health professional during the examination: as interfaces of
      the attendance.

PMID- 14686053
TI  - [Factors that influence nurses to use physical activities in the care of
      psychiatric patients].
AB  - This study addresses the importance of promoting physical activities among
      psychiatric patients and its goals were to identify the changing behavior
      potential of the nurses as well as to identify the nurse staff beliefs regarding
      the benefits of physical activity with the patients, to characterize the way in
      which these activities are managed inside the psychiatric hospital and finally,
      to identify the factors which influence the promotion of these activities in the
      mentioned environment. The fourteen nurses interviewed believe in the benefits of
      physical exercise, but only nine of them do training. We have noticed that 50% of
      them are in the action stage, 42.9% are in contemplative stage and only 7.1% are
      in the pre-contemplative stage.

PMID- 14686054
TI  - Critical thinking and accuracy of nurses' diagnoses. Part II: Application of
      cognitive skills and guidelines for self-development.
AB  - Part I of this article, the author explained the difficulties of achieving
      accuracy of nurses' diagnoses, the relevance of critical thinking to the
      achievement of accuracy, and newer views of critical thinking. In Part II, the
      critical thinking dimensions identified as important for nursing practice are
      applied in the diagnostic process using a case study of a 16 year old girl with
      type 1 diabetes. Application of seven cognitive skills and ten habits of mind
      illustrate the importance of using critical thinking for accuracy of nurses'
      diagnoses. Ten strategies are proposed for self-development of critical thinking
      abilities.

PMID- 14686055
TI  - [The length of an article].

PMID- 14686056
TI  - [Ovarian mature teratoma. Clinico-pathological study of 112 cases and review of
      the literature].
AB  - A retrospective, descriptive study of 112 patients diagnosed and treated of
      mature ovarian teratoma, between January 1995 and September 2001, at Reina Sofia
      University Hospital, was carried out. The patient's mean age is 36.2 years old
      (SD = 13.8). The most frequently symptom was abdominal pain (50.9%) though a high
      percentage of the cases (41.1%) the patients were asymptomatic. The mean size of
      the tumor was 76.2 mm (SD = 35.8) and 9.8% were bilateral. The most used
      diagnostic procedure was ultrasound with a right diagnostic of 47.6%, though
      81.3% of the cases a surgery was performed, with a preview diagnostic of ovarian
      tumor and the 53.8% with the right diagnostic of benign teratoma. 18.7% of the
      tumors was found in a laparotomy for other cause. From the 123 tumors, 96% were
      benign ovarian cyst, 1.6% mature solids teratomas and 2.4% struma ovarii. The
      most frequent surgery was unilateral oophorectomy (54.5%) and 19.6% was total
      hysterectomy with bilateral oophorectomy, with the mean age of this last ones of
      54.8 years old (SD = 12.0). The preservation of the ovarian function was in 75%
      of the patients. We will analyze our results and compare with the bibliography.

PMID- 14686057
TI  - [Influence of sperm morphology on results of intrauterine insemination].
AB  - OBJECTIVE: To determine the influence of sperm morphology, according to WHO
      criteria, on pregnancy rates of couples who were submitted to intra-uterine
      insemination (IUI). MATERIAL AND METHODS: Retrospective study that included 787
      IUI cycles performed in the Instituto para el Estudio de la Concepcion Humana in
      Monterrey, Mexico, from January to December 2002. Main diagnosis were
      anovulation, male factor, endometriosis, and cervical factor. All patients were
      allocated into a controlled ovarian hyperstimulation protocol with either
      clomiphene citrate, menotropins and/or recombinant FSH. RESULTS: A total of 115
      pregnancies were achieved (pregnancy rate per cycle of 14.61%). When seminal
      parameters were analyzed as independent factors it was found that a motility less
      than 10%, total motile count after sperm preparation less than 1 million/ml and
      sperm motility less than 20% had a pregnancy rate of zero. CONCLUSIONS: Patients
      with normal sperm forms less than 20% according to WHO criteria have no benefit
      with the IUI and these patients should be canalized to ART.

PMID- 14686058
TI  - [Comparison of the results of an assisted-reproduction program related with the
      day of follicular aspiration].
AB  - The proper time for the oocyte retrieval allow us to obtain good quality oocytes
      In assisted reproduction techniques, improving fertilization and pregnancy rates.
      The follicular aspiration has been done by vaginal ultrasounds when we can see at
      least 3 follicles > or = 16 mm diameter. OBJECTIVE: To compare oocyte quality,
      fertilization and pregnancy rate-according to the day of the follicular
      aspiration. MATERIAL AND METHODS: 438 cycles were studied in the Instituto para
      el Estudio de la Concepcion Humana in Monterrey Mexico, comparing oocyte quality,
      fertilization and pregnancy rate. RESULTS: If egg retrieval was done on day 12 of
      the cycle, we obtained a mean of 7.61 good quality oocytes, 51% of them
      fertilized and the pregnancy rate was 36.8%, when the aspiration was performed on
      day 13 of the cycle, we obtained a mean of 7 good quality oocytes, 59% of them
      fertilized and the pregnancy rate was 34%, and if the oocyte retrieval was on day
      14 of the cycle, we obtained a mean of 6.42 good quality oocytes, 57% of the
      fertilized and the pregnancy rate was 31.7%. DISCUSSION: The oocyte quality,
      fertilization and pregnancy rate were slightly better if the oocyte retrieval was
      performed on day 12 or 13 of the cycle, rather than day 14. However this was no
      statistical significative.

PMID- 14686059
TI  - [First Workshop on Gender Violence and Sexual Violence for Central America and
      Panama].

PMID- 14686060
TI  - [Identification and typification of the human papilloma virus in women using the
      "Timely Detection of Cancer" program in Durango, Mexico].
AB  - OBJECTIVE: In Mexico, the cervical carcinoma is a public health problem,
      representing more of 36% of the neoplasms. This carcinoma has been etiologically
      associated with the human papillomavirus (HPV) infection and the polymerase chain
      reaction (PCR) has been considered as one of the most sensitive methods for its
      detection. The aim of this study was to determine the HPV types by PCR-RFLPs in
      111 women attending in the DOC programs in Gomez Palacio, Durango. METHODS: DNA
      was extracted from cervix-vaginal samples as previously described and HPV were
      detectad using the primers MY09 and MY11. Viral type was determined according to
      analysis RFLPs. RESULTS: The cito-histopatologic diagnoses showed that 93 women
      did not present cervical alteration: 91 (91.85%) were negative HPV and two
      (2.15%) were VPH positive (low risk). In contrast, 18 women showed cervical
      alterations; 17 (94.44%) were VPH positive (11 of low risk and 6 of high risk)
      and only one did not present HPV infection. CONCLUSION: The distribution of types
      HPV observed in Gomez Palacio, Durango is according to previous study. This is
      essential a estimation in the development of strategies for prevention of
      cervical carcinoma in our region.

PMID- 14686061
TI  - [Arachnoid cyst and pregnancy. Report of a case].
AB  - The arachnoid cysts are intracranial liquid collections with a congenital
      etiology. It is necessary to establish the absence of bibliographical information
      about this disease and its relation with pregnancy. A case is presented related
      to the treatment of a nineteen year old pregnant patient with a 31 week pregnancy
      and a history of arachnoid cysts with convulsions as the main symptom.

PMID- 14686062
TI  - [Microbiological and serological diagnostic methods to detect intrauterine and
      perinatal infections].
AB  - Due to the revolutional development in sampling devices, transport media,
      automated equipments, microvolume probes and molecular microbiological techniques
      in the last decade new possibilities have become available for diagnosing
      microbiologically congenital infections in both the mother and the foetus and the
      newborn. This minireview gives an insight into the diagnostic tuls of clinical
      microbiology and infection serology by showing laboratory diagnostic processes of
      most frequent protozoal, viral and bacterial infections step-by-step. It exhibit
      an almost complete list of transplacental, intrauterinal and connatal infections.
      Attention is also focused to the complexity of the interrelationship between the
      clinical microbiology and infection serology data concerning the infections of
      the mother and her offspring.

PMID- 14686063
TI  - [Capsule endoscopy in small bowel diagnostics].
AB  - INTRODUCTION: Capsule endoscopy allows for the first time total and painless
      imaging of the entire small bowel. The main indication for capsule endoscopy is
      obscure gastrointestinal bleeding which not explained by upper gastrointestinal
      endoscopy, colonoscopy and small bowel radiology. Capsule endoscopy has also the
      capacity to detect tiny small bowel manifestations of other pathologic conditions
      such as Crohns's disease. METHOD AND AIMS: The GivenM2A wireless capsule
      endoscopy system for investigation of the whole small bowel was developed in the
      late 1990s. The small size swallowable capsule contains a miniature video camera,
      four light sources, two batteries and a radiotransmitter. This paper describes
      the capsule endoscopy examination method and summerizes the initial achievements
      from two medical centres, the Petz Aladar County and Teaching Hospital and from
      the Malmo University Hospital. RESULTS: 42 patients were included of whom 37
      patients with obscure gastrointestinal bleeding. Pathological small bowel
      findings were detected in 62% of the all cases, and the source of bleeding was
      identified by the M2A capsule in 56.7% of the chronic bleeders. The diagnostic
      sensitivity of the capsule endoscopy in obscure gastrointestinal bleedings was
      superior both to that of push enteroscopy, 19%, and enterography, 6.7%. The
      capsule endoscopy was well tolerated and accepted by the patients. CONCLUSIONS:
      This new diagnostic method is promising mainly for detection of a small bowel
      source of obscure bleedings. The availability of the method in major
      gastroenterological centers is strongly recommended.

PMID- 14686064
TI  - [Three-dimensional morphologic examination of normal and diseased renal
      arterioles].
AB  - INTRODUCTION: Earlier publications show the endothelial fenestration at the
      juxtaglomerular part of the afferent arteriole facing mesangial and granular
      cells and finger-like protrusions of urinary space into the region of the lacis
      in experimental animals such as the rat, the mouse, and Tupaia belangery. In
      human kidney both the endothelial fenestration in the wall of the afferent
      arteriole and protrusions with filtration slits of urinary space into the lacis,
      were observed with remarkable heterogeneity. There was found the fenestrated
      entdothelium facing the reningranulated cells of Amphiuma kidney too.
      Arteriolosclerosis frequently occurs in IgA nephritis, and is the hallmark of
      benign nephrosclerosis. The quantitative ultrastructure of juxtaglomerular
      arterioles is not known in these disorders. AIMS AND METHODS: The aim of both
      studies was to characterize the arteriolar parameters using stereology. In normal
      kidney was the permeability studied along the full length of afferent arteriole
      using ferritin particles as indicator of permeability/fenestration. In renal
      biopsies from patients with IgA nephritis and patients with benign
      nephrosclerosis the afferent and efferent arterioles were examined. Age-matched
      living renal transplant donors were used as controls. The thickness of the media
      (myomedial cells plus the matrix) and the thickness of the medial matrix were
      estimated. From these estimates, the matrix/myomedia ratio was calculated.
      RESULTS: In the normal kidney the density of ferritin particles was high close to
      the glomerulus and decreased continuously similarly to the profile of renin
      distribution. There was a correlation between the length of ferritin-positive and
      renin-positive portions. Based on these results, the afferent arteriole,
      according to its endothelial permeability, can be divided into two distinct
      portions i.e. the permeable and the non-permeable, the length and ratio of which
      may be related to the actual renin formation. In IgA nephritis with normotension
      or hypertension, the afferent media and its components did not exhibit
      significant thickening compared with the controls, whereas in benign
      nephrosclerosis the afferent media and its layers were markedly and significantly
      thickened. The efferent media in IgA nephritis and benign nephrosclerosis
      displayed mild and significant thickening, with normotension. CONCLUSION: The
      results indicate that the afferent arterioles are not the main sites of IgA
      nephritis-related arteriolosclerosis, and that benign nephrosclerosis represents
      different lesions. The stereological method was successfully used and provided
      essential information about the arterioles in both study.

PMID- 14686065
TI  - [Acute quadriplegia after diabetic ketoacidosis].
AB  - A 36-year-old female was admitted to the intensive care unit after resuscitation
      diagnosed with diabetic ketoacidotic coma, which was the first manifestation of
      her diabetes mellitus. It may have been provoked by pulmonary or gastrointestinal
      coinfection. Five days following admission the patient regained consciousness and
      homeostasis returned to normal. One week after the stabilization of her
      cardiopulmonary state, weaning from the respirator turned out to be unsuccessful:
      flaccid tetraparesis developed with rapid muscle atrophy and absence of deep
      tendon reflexes. The sensory system and cranial nerves remained intact.
      Electrophysiological studies and muscle biopsy showed serious acute illness
      myopathy with mild demyelination owing probably to the latent diabetes. The
      course of acute quadriplegia was fluctuating and correlated mainly with the
      activity of the systemic inflammatory response syndrome mechanisms. Myopathy
      might have been aggravated by using high-dose glucocorticoid therapy. The
      patient's general condition improved quickly as a result of full recovery from
      sepsis, discontinuation of glucocorticoids and normoglicaemia maintained by
      subcutan insulin substitution. Eight months after admission almost full
      neuromuscular restitution was achieved showing the reversibility of this grave
      illness.

PMID- 14686066
TI  - [Therapy of adult type-2 diabetes mellitus].

PMID- 14686067
TI  - With the new DLA forms we have come full circle--to a process that once again
      silences the claimant.

PMID- 14686068
TI  - A brave new world of health care.

PMID- 14686069
TI  - Taking steps toward long-term viability.

PMID- 14686070
TI  - HIPAA copy charges for medical records.
AB  - The HIPAA privacy rule allows providers to charge for providing copies of medical
      records to patients and their representatives. Providers need to know which
      activities in the retrieval and handling of such information can be included in
      the medical record copy charges. State-mandated fees for copies vary and may be
      preempted by HIPAA, requiring careful review by providers. Healthcare
      organizations that use a copy service may need to determine whether bringing the
      activity in house would be more cost-effective under HIPAA.

PMID- 14686071
TI  - Recovering real money with a contract management system.
AB  - A payment error here, a payment error there--pretty soon, you're talking about
      real money. Contract and underpayment management systems can pay for themselves
      by unearthing tiny errors that add up to a lot of lost cash.

PMID- 14686072
TI  - The collector inspector. Self-pay trends necessitate more effective RFPs.
AB  - A rise in the self-pay patient population requires healthcare providers to place
      increasing significance on the collection agencies they contract with. To best
      examine competing agencies and choose effective candidates, providers should
      develop a well-designed format for the request for proposal. Specific areas of
      interest should include the vendor's business philosophy, measurements of
      performance, and staff qualifications.

PMID- 14686073
TI  - Payment trends. Achieving stability amid uncertainty.

PMID- 14686074
TI  - What's it worth?
AB  - Patients without effective coverage frequently must pay charges for medical
      services that are higher than the hospital's contracted rates. A national survey
      of hospitals shows great variation in how charges are set and accommodations made
      for patients with low income. The government is taking a more active role in
      examining charging practices. Hospitals can take several steps to help stave off
      government intervention.

PMID- 14686075
TI  - Dedicating the right resources to denials management.

PMID- 14686077
TI  - Strong leadership can help avoid nightmares.

PMID- 14686076
TI  - Strategic service-line planning. Building competitive advantage.
AB  - Service-line planning requires a healthcare organization to develop a business
      plan for each of its service lines. Successful service-line planning requires top
      leadership support, a willingness to allocate resources, the development of
      support mechanisms, the active support and involvement of physicians, and
      management commitment and accountability during implementation.

PMID- 14686078
TI  - Financially savvy system implementation: tips you need to know.

PMID- 14686079
TI  - EMG reactivity and oral habits among young adult headache sufferers and painfree
      controls in a scheduled-waiting task.
AB  - Previous research has shown that patients with facial pain exhibit a pattern of
      physiological and behavioral reactivity to scheduled-waiting tasks that may help
      account for the development of facial pain. The present study extended this line
      of research by examining the psychophysiological reactivity of headache sufferers
      in a similar task. A total of 34 frequent headache sufferers screened by
      International Headache Society (IHS) criteria and 13 painfree controls completed
      a psychophysiological assessment consisting of 4 phases (adaptation, free-play,
      scheduled-play, and recovery) that included a scheduled-waiting condition
      (scheduled-play) designed to produce adjunctive behavior. Masseter and frontalis
      EMG were measured continuously during each phase and self-reported oral habits
      and pain ratings were collected following each phase. A significant interaction
      and group effect was found on frontalis EMG, with the headache group exhibiting
      elevated EMG levels across the phases, whereas the control group exhibited
      increasing EMG levels that peaked during the scheduled-play phase. Only a
      significant phase effect was found on masseter EMG, with the highest EMG levels
      recorded during the scheduled-play phase for both groups. In addition, a
      significant phase effect was found on self-reported oral habits data. Overall,
      these results provide general support for the adjunctive behavior effect, but the
      predicted difference in magnitude between the groups was not found.

PMID- 14686080
TI  - Posttraumatic headache: an exploratory treatment study.
AB  - Fourteen patients with posttraumatic headache (PTHA) were treated with a
      comprehensive treatment package targeting headache symptoms along with associated
      posttraumatic stress symptoms. Treatment consisted of some or all of the
      following depending on headache features: thermal biofeedback, electromyography
      biofeedback targeting the forehead and/or neck muscles, progressive muscle
      relaxation, education and cognitive-behavioral therapy. Mean improvement for the
      treatment group was 21%, whereas mean improvement for the wait-list group was-
      14% indicating a worsening of headache; however, the difference between groups
      was not statistically significant. There was a significant between groups
      difference on headache-free days. Within group results were modest with 29% mean
      improvement by the end of treatment. The reduction in headache index was
      significant. Minor reductions in psychopathology, most notably anxiety, were
      found after treatment. This study confirmed the treatment difficulties seen in
      this understudied population of headache sufferers, but offered hope for symptom
      relief.

PMID- 14686081
TI  - The use of thermal biofeedback in the treatment of pain associated with
      endometriosis: preliminary findings.
AB  - Endometriosis is a common gynecological disease that causes marked physical and
      emotional distress in lives of women, resulting in dysmenorrhea, pain, or both
      throughout the menstrual cycle in over 96% of cases. A multiple case study design
      (N = 5) was employed to investigate the use of thermal biofeedback in the
      treatment of pain associated with endometriosis. The majority of participants (4
      out of 5) were able to demonstrate mastery over hand temperature through thermal
      biofeedback. Of those participants, significant reductions in various aspects of
      pain were observed by the end of the study; one had a significant increase in
      Life Control; two had reductions in Pain Severity; three had a decrease in
      Affective Distress; and all 4 demonstrated reduction in Life Interference, as
      measured by the West Haven-Yale Multidimensional Pain Inventory. This is a
      preliminary study with a small sample size and without a control sample; hence,
      the results are considered only as suggestive of the potential use of biofeedback
      therapy in alleviating pain and associated symptomatology related to
      endometriosis. Further research is warranted.

PMID- 14686082
TI  - Applied psychophysiology: beyond the boundaries of biofeedback (mending a wall, a
      brief history of our field, and applications to control of the muscles and
      cardiorespiratory systems).
AB  - The field of applied psychophysiology overlaps a number of others, from
      behavioral and psychosomatic medicine to Eastern disciplines and complementary
      medicine. Although the proliferation of societies and professional identities
      across these fields emphasizes this diversity, it also may hinder growth. The
      history of our field is one of innovation, often at odds with conventional wisdom
      and practice. It is important that this innovativeness not be sacrificed in a
      justified quest for professional respectability. This paper reviews the earliest
      research in biofeedback and applied psychophysiology, and modern applications and
      interpretations in the areas of muscular and autonomic control, including
      progressive relaxation and heart rate variability biofeedback, and draws
      parallels to disciplines of Yoga, QiGong, and Zen practices and their
      psychophysiological effects.

PMID- 14686083
TI  - Up close and personal: a case study of the development of three English fillers.
AB  - As Peters (2001) has suggested, the young child's use of fillers seems to
      indicate awareness of distributionally-defined slots in which some as yet
      unidentified material belongs. One may view a filler as an emergent transitional
      form; as a slot that serves as an underspecified lexical entry for the
      accumulation of phonological and functional information; or as prosodic 'sentence
      padding'. We trace the development of three fillers in one English-acquiring
      child through seven months, from their first appearance about 1;9 through their
      re-analysis as English functors about age 2;4. We show how the description of
      these fillers requires an elaboration of the current framework for describing the
      emergence of morphology, from a one-dimensional to a multi-dimensional model.
      Finally, we argue that the neglect of such transitional and under-defined
      elements gives a false picture of development, making it appear as if language
      development takes place in discontinuous steps.

PMID- 14686084
TI  - The use of grammatical morphemes reflecting aspect and modality by children with
      specific language impairment.
AB  - Children with specific language impairment (SLI) have well-documented problems in
      the use of tense-related grammatical morphemes. However, in English, tense often
      overlaps with aspect and modality. In this study, 15 children with SLI (mean age
      5;2) and two groups of 15 typically developing children (mean ages 3;6 and 5;3)
      were compared in terms of their use of previously studied morphemes in contexts
      that more clearly assessed the role of aspect. The children's use of less
      frequently studied morphemes tied to modality or tense was also examined. The
      children with SLI were found to use -ing to mark progressive aspect in past as
      well as present contexts, even though they were relatively poor in using the
      tense morphemes (auxiliary was, were) that should accompany the progressive
      inflection. These children were inconsistent in their use of third person
      singular -s to describe habitual actions that were not occurring during the time
      of their utterance. However, the pattern of the children's use suggested that the
      source of the problem was the formal tense feature of the inflection, not the
      habitual action context. The children's use of modal can was comparable to that
      of the typically developing children, raising the possibility that the modality
      function of possibility had been learned without necessarily acquiring the tense
      feature of this morpheme. These children's proficiency with can suggests that
      their bare verb stem productions should probably not be re-interpreted as cases
      of missing modals. Together these findings suggest that the more serious tense
      related problems seen in English-speaking children with SLI co-occur with a less
      impaired ability to express temporal relations through aspect and modality.

PMID- 14686086
TI  - The sources of young children's name innovations for novel artifacts.
AB  - Two studies investigated whether four-year-old children (12 in Experiment 1 with
      a mean age of 4;8 and 36 in Experiment 2 with a mean age of 4;7) invent names for
      new artifacts based on the objects' functions as opposed to their perceptual
      properties. Children informed about the intended functions of novel objects
      provided more name innovations that were clearly function-based than perception
      based. This tendency was observed when children were shown the objects'
      functions, even if they were also given verbal descriptions of the objects'
      perceptual properties and parts. Only when ignorant of the objects' intended
      functions did children tend to use perceptual features to create substantial
      numbers of names. Accordingly, results from this name-innovation methodology
      converge with findings from some recent studies of lexical categorization
      suggesting that functional information is critical to how preschoolers extend
      artifact names. Children appear to appreciate an intimate relation between the
      functions of artifacts and how they are named.

PMID- 14686085
TI  - Rules and construction effects in learning the argument structure of verbs.
AB  - Theorists of language acquisition have long debated the means by which children
      learn the argument structure of verbs (e.g. Bowerman, 1974, 1990; Pinker, 1984,
      1989; Tomasello, 1992). Central to this controversy has been the possible role of
      verb semantics, especially in learning which verbs undergo dative-shift
      alternation in languages like English. The learning problem is somewhat
      simplified in Bantu double object constructions, where all applicative verbs show
      the same order of postverbal objects. However, Bantu languages differ as to what
      that order is, some placing the benefactive argument first, and others placing
      the animate argument first. Learning the language-specific word-order
      restrictions on Bantu double object applicative constructions is therefore more
      akin to setting a parameter (cf. Hyams, 1986). This study examined 100 three- to
      eight-year-old children's knowledge of word order restrictions in Sesotho double
      object applicatives. Performance on forced choice elicited production tasks found
      that four-year-olds showed evidence of rule learning, although eight-year-olds
      had not yet attained adult levels of performance. Further investigation found
      lexical construction effects for three-year-olds. These findings suggest that
      learning the argument structure of verbs, even when lexical semantics is not
      involved, may be more sensitive to lexical construction effects than previously
      thought.

PMID- 14686087
TI  - The emergence of grammar: early verbs and beyond.
AB  - The paper examines the first twenty verb-forms recorded for six Hebrew-speaking
      children aged between 1;2 and 2;1, and how they evolve into fully inflected verbs
      for three of these children. Discussion focuses first on what word-forms children
      initially select for the verbs they produce, what role these forms play in
      children's emergent grammar, and how emergent grammar is reflected in the
      acquisition of fully inflected forms of verbs. Children's early verb repertoire
      indicates that they possess a strong basis for moving into the expression of a
      variety of semantic roles and the syntax of a range of different verb-argument
      structures. On the other hand, children's initial use of verbs demonstrates that
      they still need to acquire considerable language-particular grammatical knowledge
      in order to encode such relations explicitly. This language-particular knowledge
      demonstrates a clear pattern of acquisition, in which aspect precedes
      inflectional marking for gender, followed by tense, and then by person.

PMID- 14686088
TI  - Possible explanations for children's literal interpretations of homonyms.
AB  - This study was designed to examine factors associated with literal
      interpretations of homonyms. Participants were 212 second graders, ages 7;0-8;11,
      who listened to a story containing 16 key words. The key words were homonymous
      words ('pseudo-homonyms'), nonsense words, or familiar words used accurately.
      While listening to the story, children selected an illustration of each key word.
      Later, they were asked to recall the key words and to justify their picture
      selections. There was no association between interpretation and recall accuracy
      for nonsense words or familiar words used accurately; however, children who
      accurately recalled a homonymous key word were more likely to interpret the
      homonym 'literally,' relative to children who failed to recall the key word. Yet
      most of the children who correctly interpreted the pseudohomonyms also correctly
      interpreted these key words. Most children correctly recalled the story context
      regardless of key word type, but whereas correct recall of context predicted
      accurate interpretation of nonsense words and familiar words used accurately, it
      did not do so for homonyms. Children made equivalent numbers of literal and
      accurate interpretations of homonyms, even when correctly recalling context.
      Children's justifications for their word interpretations implicated the role of
      metacognitive skills, particularly in terms of selective attention, as a factor
      influencing homonym interpretation.

PMID- 14686089
TI  - Do word learners ignore ignorant speakers?
AB  - Thirty-six three- to four-year-old children were tested to assess whether hearing
      a word-referent link from an ignorant speaker affected children's abilities to
      subsequently link the same word with an alternative referent offered by another
      speaker. In the principal experimental conditions, children first heard either an
      ignorant or a knowledgeable speaker link a novel word with one of three toys. The
      first speaker's labelling episode was followed by a second in which a different
      speaker used the same novel label but for a different toy. There was also a Base
      line condition which was the same as the experimental condition involving the
      ignorant speaker except that she did not associate the novel label with a
      referent. When tested for comprehension of the novel label, children selected the
      FIRST speaker's toy at high levels when the first speaker was knowledgeable, but
      selected the SECOND speaker's toy when the first speaker was ignorant. These
      findings suggest that children's experience with the ignorant speaker did not
      affect their abilities to learn a subsequently presented alternative word
      referent link. These findings are discussed in terms of understanding the
      mechanisms by which children adapt their word-learning in line with speakers'
      knowledge states.

PMID- 14686090
TI  - Can exercise stress facilitate innate immunity? A functional role for stress
      induced extracellular Hsp72.

PMID- 14686091
TI  - Chaperokine-induced signal transduction pathways.
AB  - A turning point in understanding the function of heat shock proteins (HSP) on
      components of the immune system has now begun. From their original description as
      intracellular molecular chaperones of naive, aberrantly folded or mutated
      proteins and primarily involved in cytoprotection in response to stressful
      stimuli, in recent years, new functions of HSP have been revealed. Strong
      evidence now exists demonstrating that the seventy-kDa heat shock protein (HSP70)
      exits mammalian cells not only following necrotic cell death but also by a
      process involving its active release in response to stresses including cytokines,
      acute psychological stress and exercise. The released extracellular HSP70
      interacts with cells of the immune system and exerts immunoregulatory effects-
      known as the chaperokine activity of HSP70. The chaperokine activity of HSP70 is
      mediated in part by utilizing surface receptors for both Toll-like receptor-2
      (TLR2; receptor for Gram-positive bacteria) and TLR4 (receptor for Gram-negative
      bacteria) in a CD14-dependent fashion. These findings suggest an important role
      for heat shock proteins in host protection against pathogenic infection. This
      review will briefly discuss chaperokine-induced signaling and its relevance to
      infection and exercise.

PMID- 14686092
TI  - Signaling pathways for IL-6 within skeletal muscle.
AB  - Over the past 5 years it has become apparent that cytokines are produced by
      myocytes in the absence of any markers of inflammation. Specifically, the gene
      encoding for the cytokine interleukin (IL)-6 is present in skeletal muscle and is
      induced by muscle contraction and, in some circumstances by insulin. In turn, IL
      6 protein is produced throughout the myocyte and released into the circulation
      where it acts in an "endocrine like" manner to activate processes designed to
      maintain metabolic homeostasis. Hence, it has become apparent that IL-6 may be a
      factor that is coupled to genes involved in metabolic processes both within
      skeletal muscle and adipose tissue. Relatively less is known regarding the
      upstream factors that induce the transcription of IL-6. However, it is clear that
      IL-6 production is activated by intracellular calcium levels, mitogen-activated
      protein kinases, reduced glycogen availability and other cytokines such as IL-1
      beta. This review will briefly discuss the signaling pathways involved in IL-6
      gene transcription.

PMID- 14686093
TI  - The role of IL-6 in exercise-induced immune changes and metabolism.
AB  - Cytokines such as interleukin (IL)-6 are proteins, which were originally
      discovered within the immune system. Recent studies, however, demonstrate that IL
      6 is produced by, and released from contracting skeletal muscles during exercise.
      This release occurs in the absence of muscle damage and is related to both
      contraction per se and low muscle glycogen. IL-6 seems to work as an energy
      sensor within the muscle cells. Other organs also release IL-6 during exercise;
      however, muscle-derived IL-6 seems to play an important role in signalling
      between the muscles and other organs in order to maintain energy supply. IL-6 can
      enhance lipolysis in humans and might play a role in glucose metabolism. In
      addition, muscle-derived IL-6 is likely to initiate many of the exercise
      associated immune changes, as IL-6 can increase plasma levels of the cytokines IL
      1 ra and IL-10, together with cortisol and blood neurtrophils. Also, the observed
      shift towards Th2 lymphocyte dominance during exercise may be mediated by IL-6.
      Because carbohydrate ingestion during exercise has been demonstrated to blunt the
      IL-6 and hormonal response, it might also blunt other beneficial adaptations.
      This review discusses the possible beneficial biological role of high plasma
      levels of IL-6 during exercise.

PMID- 14686094
TI  - Exhaustive exercise and type-1/type-2 cytokine balance with special focus on
      interleukin-12 p40/p70.
AB  - It is known that interleukin (IL)-12 p70 promotes the differentiation of type-1
      helper T (Th1) cells, which produce type-1 cytokines such as IL-2 and interferon
      (IFN), thereby supporting cellular immunity, whereas IL-12 p40 acts as an
      antagonist of IL-12 p70. In contrast, IL-4 and IL-6 promote the differentiation
      of Th2 cells, which produce type-2 cytokines IL-4, IL-6 and IL-10, induce humoral
      immunity and are involved in allergic reactions. Exhaustive exercise causes the
      suppression of T lymphocyte activity while asthmatic and allergic diseases are
      subclinically more prevalent in athletes. One of the mechanisms behind these
      observations might be a lower type-1 and higher type-2 cytokine balance, which we
      previously demonstrated to occur after exhaustive exercise. In the present study,
      we investigated the type-1/type-2 cytokine balance by measuring plasma
      concentrations of IL-2, IL-4, IL-5, IL-10, tumor necrosis factor (TNF)-alpha and
      IFN-gamma with microparticle-based flow cytometric technology. IL-5, IL-6 and IL
      13 were measured by enzyme-linked immunosorbent assay (ELISA). IL-12 p40 and p70
      were measured separately, also by ELISA. Plasma IL-12 p40 concentration rose
      significantly after maximal exercise and to an even greater extent after a
      marathon race. Conversely, plasma IL-12 p70 could not be detected even using two
      different assays. The marathon race caused a marked increase in the plasma
      concentrations of IL-6 and IL-10. Their responses were correlated (r = 0.78, p <
      0.01), indicating that IL-6 is an inducer of IL-10, and may partly induce the
      type-1 < type-2 cytokine balance. With the exception of one study involving
      maximal exercise, other studies have failed to show any change in circulating IL
      12 concentration with exercise. The present study demonstrated that IL-12 p40 was
      present in excess of p70 especially after exercise. This may be one of the
      mechanisms behind several phenomena including cellular immunosuppression, an
      increase in the relative proportion of type-2 cytokines following exhaustive
      exercise, and the higher incidence of infections and allergic disorders in
      regularly exercising endurance athletes.

PMID- 14686095
TI  - Microarray technology--the future analyses tool in exercise physiology?
AB  - Microarray analysis offers a set of analytical platforms that provide rapid,
      affordable and substantial information at the DNA, RNA or protein level. It
      enables the analysis of thousands of genes simultaneously in a parallel manner
      across samples derived from various biological sources and treatment regimens.
      This development became possible as a result of the combination of three
      technological advances achieved at the beginning of the 1990's, namely
      parallelism, miniaturization and automation. In regular physical checkups the
      microarray technology could be used to supplement the current spectrum of tests
      and therefore enhance the quality of the data obtained. Arrays for analyses of
      RNA expression will allow gene expression profiling also in exercise physiology.
      DNA chips may also be used for genetic screening and diagnostics to analyze
      polymorphisms and mutations which may underlie genetic diseases or
      interindividual variations between subjects. Using microarrays in exercise
      physiology will provide new insights into the complex molecular mechanisms of the
      exercise-induced stress response, adaptation to training and modulation of immune
      function. Gene expression profiling and genetic screening will probably help to
      characterize and predict the individually variable response to and efficiency of
      training.

PMID- 14686096
TI  - Neuroendocrine mediators in the modulation of phagocytosis by exercise:
      physiological implications.
AB  - Neuroendocrine mediation of the effects of exercise on macrophage and neutrophil
      phagocytosis, the organism's first line of defense against external aggression,
      is reviewed. Exercise modulates the immune system via the actions of "stress
      hormones". Although stress had long been regarded as generally immunosuppressive,
      it is now accepted that this is not always true. Indeed exercise-induced stress
      stimulates the "phagocytic process" of phagocytes. One of the new physiological
      interpretations emerging from recent studies is that the general stimulation of
      phagocytosis and other innate mechanisms during strenuous physical activity may
      counterbalance the decreased lymphoid activity, preventing the entry and survival
      of microorganisms in situations where the specific responses are depressed. In
      some cases this behaviour is also medicated by "stress hormones", unlike in
      lymphocytes in which glucocorticoids and catecholamines both are
      immunosuppressive. The mediatory role of glucocorticoids in macrophages may also
      differ between the non-specific functions, like chemotaxis and phagocytosis, and
      the more specific ones, like antigen-presentation. Neutrophils and monocytes may
      be stimulated by catecholamines or sympathetic signals, and variations in
      phagocytosis and catecholamines have been proposed as a good "neuroimmuno
      endocrinological marker" in athletes. Other hormones (prolactin, GH, endorphins,
      thyroid hormones) in general also contribute to the effects of exercise-stress on
      phagocytosis. This review focuses on a physiological interpretation of the immune
      response to exercise which differs markedly from the classical immunosuppression
      centered view. More studies on in vivo variations of stress hormones during
      exercise are needed.

PMID- 14686097
TI  - Evidence-based medicine: why clinical ethicists should be concerned.
AB  - Evidence-based medicine purports to be the integration of three prongs; best
      research evidence, clinical expertise, and patient values and preferences.
      Controversy still surrounds the application of evidence-based medicine and
      undoubtedly controversy will persist in the treatment of specific diseases, thus
      allowing for some flexibility in decision-making. Yet, the idea that variation is
      expensive has gained wide acceptance and variation can best be controlled through
      rigid systems. So given the financial constraints facing healthcare
      organizations, as well as pressure from such august organizations like the
      Institute of Medicine to implement evidence-based medicine, flexibility in
      decision-making may ultimately become the exception rather than the rule.
      Certainly, in the short-term, the advantages of a rigid system, notably its cost
      advantage, overwhelm the advantages of a more naturally adaptive system--and so
      where possible evidence-based medicine will probably be implemented within a
      rigid context. Rigidity in system design will affect the activities of clinical
      ethics. To be effective in such a system, clinical ethicists will need an
      understanding of the system within which they practice including its values,
      goals, operations, and tools. This is a knowledge area which few in this field
      currently have and which they may not wish to acquire. But, if clinical ethicists
      expect to have credibility in responding to these changes, they must understand
      the values, goals, processes and outcomes of the system in place and be able to
      advocate for greater flexibility and greater attention to patient values and
      preferences even within a rigid mechanical system.

PMID- 14686098
TI  - Mixed feelings: physicians' concerns about clinical ethics committees in Germany.

PMID- 14686099
TI  - Life extension technologies: economic, psychological, and social considerations.

PMID- 14686100
TI  - Should a medical/surgical specialist with formal training in bioethics provide
      health care ethics consultation in his/her own area of speciality?

PMID- 14686101
TI  - The impact of committee characteristics on the success of healthcare ethics
      committees.
AB  - Despite the increase in number and importance of healthcare ethics committees
      (HECs), little is known about how successful HECs are and what characteristics
      contribute to their success. The current study attempted: (1) to examine the
      effect of respondent backgrounds on the self-reported success and characteristics
      of HECs, (2) to describe the current success status of HECs, and (3) to explore
      how committee characteristics are related with the success. Questionnaires on
      characteristics of respondents and committees as well as the rating of success
      were distributed to 962 acute care hospitals with 300 beds or more across the
      United States in the calendar year 2000. A total number of 294 chairpersons and
      223 members from 334 ethics committees responded to the survey, yielding a 35%
      response rate. Statistical analyses on the survey data found that the length of
      services on committees (seniority) and the size of committees were significant
      contributors to the perceived success of committees. The significant association
      of seniority suggests that future studies should control for the effect of
      seniority, possibly using multivariate modeling methods. The more success
      perceived by large committees indicates a need for small committees to increase
      the size of their committees so that they can expand their expertise to resolve
      the wide variety of current issues.

PMID- 14686102
TI  - Small-angle scattering: a view on the properties, structures and structural
      changes of biological macromolecules in solution.
AB  - A self-contained presentation of the main concepts and methods for interpretation
      of X-ray and neutron-scattering patterns of biological macromolecules in
      solution, including a reminder of the basics of X-ray and neutron scattering and
      a brief overview of relevant aspects of modern instrumentation, is given. For
      monodisperse solutions the experimental data yield the scattering intensity of
      the macromolecules, which depends on the contrast between the solvent and the
      particles as well as on their shape and internal scattering density fluctuations,
      and the structure factor, which is related to the interactions between
      macromolecules. After a brief analysis of the information content of the
      scattering intensity, the two main approaches for modelling the shape and/or
      structure of macromolecules and the global minimization schemes used in the
      calculations are presented. The first approach is based, in its more advanced
      version, on the spherical harmonics approximation and relies on few parameters,
      whereas the second one uses bead models with thousands of parameters. Extensions
      of bead modelling can be used to model domain structure and missing parts in high
      resolution structures. Methods for computing the scattering patterns from atomic
      models including the contribution of the hydration shell are discussed and
      examples are given, which also illustrate that significant differences sometimes
      exist between crystal and solution structures. These differences are in some
      cases explainable in terms of rigid-body motions of parts of the structures.
      Results of two extensive studies--on ribosomes and on the allosteric protein
      aspartate transcarbamoylase--illustrate the application of the various methods.
      The unique bridge between equilibrium structures and thermodynamic or kinetic
      aspects provided by scattering techniques is illustrated by modelling of
      intermolecular interactions, including crystallization, based on an analysis of
      the structure factor and recent time-resolved work on assembly and protein
      folding.

PMID- 14686103
TI  - Chaperonin-mediated protein folding: fate of substrate polypeptide.
AB  - Chaperonins are megadalton ring assemblies that mediate essential ATP-dependent
      assistance of protein folding to the native state in a variety of cellular
      compartments, including the mitochondrial matrix, the eukaryotic cytosol, and the
      bacterial cytoplasm. Structural studies of the bacterial chaperonin, GroEL, both
      alone and in complex with its co-chaperonin, GroES, have resolved the states of
      chaperonin that bind and fold non-native polypeptides. Functional studies have
      resolved the action of ATP binding and hydrolysis in driving the GroEL-GroES
      machine through its folding-active and binding-active states, respectively. Yet
      the exact fate of substrate polypeptide during these steps is only poorly
      understood. For example, while binding involves multivalent interactions between
      hydrophobic side-chains facing the central cavity of GroEL and exposed
      hydrophobic surfaces of the non-native protein, the structure of any polypeptide
      substrate while bound to GroEL remains unknown. It is also unclear whether
      binding to an open GroEL ring is accompanied by structural changes in the non
      native substrate, in particular whether there is an unfolding action. As a
      polypeptide-bound ring becomes associated with GroES, do the large rigid-body
      movements of the GroEL apical domains serve as another source of a potential
      unfolding action? Regarding the encapsulated folding-active state, how does the
      central cavity itself influence the folding trajectory of a substrate? Finally,
      how do GroEL and GroES serve, as recently recognized, to assist the folding of
      substrates too large to be encapsulated inside the machine? Here, such questions
      are addressed with the findings available to date, and means of further resolving
      the states of chaperonin-associated polypeptide are discussed.

PMID- 14686104
TI  - Ahaptoglobinemia (HpO) and malaria in India.
AB  - Haptoglobin (Hp) polymorphism analysed among P. vivax and P. falciparum patients
      and malaria negative subjects from areas with different epidemiological
      situations had shown high incidence of ahaptoglobinemia (HpO) among malaria
      patients. A definite association of HpO with P. vivax as well as P. falciparum
      malaria in Indian subjects had been observed. However, low sensitivity and
      reliability of HpO index indicates that it can not be a good indicator for
      determination of malaria endemicity. About 75 per cent of HpO subjects with P.
      vivax infection when treated with chloroquine showed typable Hp polymorphs by 8-9
      days of post-treatment.

PMID- 14686105
TI  - Evaluation of repellent action of neem oil against the filarial vector, Culex
      quinquefasciatus (Diptera: Culicidae).
AB  - Studies were carried out to evaluate the repellent action of neem oil against
      Culex quinquefasciatus. Application of 2 and 5 per cent neem oil @ 5
      ml/person/night gave 50 and 40.9 per cent protection in indoor collections and
      17.4 and 5.6 per cent in outdoor collections as compared with that of untreated
      control respectively. The protection time ranged from 0100 to 0300 hrs and 0100
      to 0600 hrs in indoor and outdoor collections respectively. Results of repellent
      action of Autan, a synthetic mosquito repellent studied concurrently showed a
      relatively higher protection rate from the bites of Cx. quinquefasciatus.

PMID- 14686106
TI  - Atypical manifestations of Plasmodium vivax malaria.
AB  - About 110 patients were enrolled to study the atypical presentations and the
      chloroquine sensitivity pattern of Plasmodium vivax malaria. The diagnosis was
      made from Giemsa stained peripheral blood smear. The co-infection of falciparum
      malaria was excluded both by smear and ParaSight F-test. After a thorough
      clinical work up, biochemical investigations were done. The fever clearance and
      parasite clearance time were determined in all cases. Absence of malarial
      paroxysm (22.8 per cent), migrainous headache (4.5 per cent), myalgia (6.3 per
      cent), episodic urticarial rash (1.8 per cent), relative bradycardia (13.6 per
      cent) and postural hypotension (2.7 per cent) were the atypical manifestations
      encountered. Besides this, severe forms like jaundice (7.2 per cent), cerebral
      involvement (0.9 per cent), severe anaemia (7.2 per cent), thrombocytopenia (3.6
      per cent) and pancytopenia (0.9 per cent) had been detected. All, except the
      patient with cerebral involvement were treated with chloroquine patients
      responded well to the treatment except two (1.8 per cent) patients who had
      chloroquine resistance. This study showed that vivax malaria can present with
      atypical and protean manifestations. The changing clinical profile along with
      development of chloroquine resistance may be considered as a warning signal.

PMID- 14686107
TI  - Enhancement of antimalarial activity of chloramphenicol against Indian Plasmodium
      falciparum isolates in vitro by chloroquine.
AB  - The antimalarial activity of chloramphenicol, a broad-spectrum antibiotic was
      studied in three Indian Plasmodium falciparum isolates having high or low
      sensitivity to chloroquine. The antimalarial activity was evaluated in 72 hours
      culture in the presence of various doses of chloramphenicol alone or in
      combination with a fixed dose of chloroquine added at a concentration that is
      well tolerated by parasites in vitro. Significant growth inhibition with
      chloramphenicol was observed at concentrations above 10 micrograms/ml in three
      isolates. However, an increase in the antimalarial activity of the compound at
      low concentrations in the range of 0.25-2.5 micrograms/ml has also been observed
      in the presence of chloroquine. Parasite growth was significantly inhibited in
      chloroquine resistant parasites. Use of chloramphenicol with chloroquine may be
      useful as a combination therapy to improve efficacy of the antimalarials and to
      retard the development of resistance to the individual components of the
      combination.

PMID- 14686108
TI  - Relative efficacy of five synthetic pyrethroids against four vector mosquitoes,
      Anopheles culicifacies, Anopheles stephensi, Culex quinquefasciatus and Aedes
      aegypti.

PMID- 14686109
TI  - Detection of Plasmodium falciparum-IgG and incidence of asymptomatic malaria in
      pregnant women in Nigeria.

PMID- 14686111
TI  - Detection of two cases of Plasmodium malariae in Jharkhand.

PMID- 14686110
TI  - Situation of malaria in forest-fringed villages of north Lakhimpur District,
      Assam.

PMID- 14686112
TI  - Anti-neutrophil cytoplasmic antibodies (ANCA) in malaria.
AB  - Various autoantibodies like anti-nuclear antibodies (ANA), anti-double stranded
      DNA (anti-dsDNA), anti-histone antibodies (AHA), anti-neutrophil cytoplasmic
      antibodies (ANCA), anti-myeloperoxidase (anti-MPO), anti-proteinase3 (anti-PR3)
      and anti-lactoferrin (anti-LF) antibodies were studied in 173 acute hospitalised
      patients suffering from malaria of which 160 patients had P. falciparum and
      remaining 13 had P. vivax infection. Standard methods like indirect
      immunofluorescence (IIF) microscopy along with Confocal microscopy and ELISA were
      used for identifying and quantifying the autoantibodies and IIF patterns on PMN
      and HL-60 cells were studied for ANCA classification. Also HEp-2 cells were used
      for ANA detection, while estimation of anti-dsDNA, AHA, anti-MPO, anti-PR3 and
      anti-LF were tested using ELISA. Sera from malaria patients showed prominent
      immunofluorescence staining patterns where 23.8% cases had ANA in P. falciparum
      group as compared to 15.4% in P. vivax group and ANCA was found to be present in
      20% in P. falciparum and 15.4% in P. vivax group. An interesting observation was
      that, of the total ANCA positives, 59% had p-ANCA, 5.9% had c-ANCA and 44.1% of
      the cases showed the 'atypical' or X-ANCA pattern. When p-ANCA positivity was
      compared with c-ANCA positivity among these patients, a good statistical
      correlation was noted with OR = 16, chi 2 = 16.43, EF = 0.46 and p-value = 5.037E
      0.5. ELISA showed 31.2% anti-MPO and 6.2% anti-PR3 in P. falciparum cases while
      the two ANCA positive cases in P. vivax had anti-MPO. Anti-LF was found to be
      present in 40.6% cases. Neither the P. falciparum nor P. vivax contained
      autoantibodies with specificities similar to the characteristic lupus
      autoantibodies such as double stranded DNA (dsDNA). ANCA positivity develops in
      some types of malarial infection also with the presence of various autoantibodies
      which is important from a clinical point of view and should be carefully
      evaluated in those geographic areas where malaria is endemic. It also alerts us
      to the fact, whether in cases of repeated malarial infections in susceptible
      individuals, vasculitic disorders, which through ANCA pathways develop, could
      lead to renal and other complications.

PMID- 14686113
TI  - Prevalence of asymptomatic malaria parasitaemia amongst pregnant women.
AB  - Two hundred and forty-six apparently healthy pregnant women aged 19-40 years,
      without symptoms were recruited (147 recruited during the dry season and 99
      recruited during the rainy season) for the present study. Blood examinations for
      malaria parasites, Plasmodium falciparum specific-IgG concentration and
      serological reactivity with P. falciparum-histidine rich protein-2 (HRP-2)
      antigens were conducted on all the pregnant women during the dry and rainy
      seasons of the year. During the dry season, 109 (74%) of the recruited pregnant
      women without symptoms had P. falciparum parasitaemia, while 79 (80%) of the
      recruited pregnant women without symptoms had P. falciparum parasitaemia during
      the rainy season. However, the P. falciparum malaria parasites density was
      significantly raised during the dry season compared with that of in the rainy
      season (p < 0.05). Serological analysis with P. falciparum histidine rich protein
      2 antigen (HRP-2) showed 108 (73%) and 71 (77%) of the pregnant women without
      symptoms as seropositive during the dry and rainy seasons respectively. The P.
      falciparum specific-IgG concentration was similar during both seasons in the HRP
      2 seropositive pregnant women without symptoms (p > 0.05). The results showed no
      seasonal tide in the incidences of asymptomatic P. falciparum parasitaemia;
      however, the significantly raised parasitaemia during the dry season may suggest
      possible increased parasites tolerance. The P. falciparum specific-IgG
      concentration during both seasons may not be the primary effector mechanism
      offering tolerance in asymptomatic parasitaemia in pregnant women.

PMID- 14686114
TI  - Operational feasibility and bio-efficacy of alphacypermethrin (Fendona) treated
      jute curtains to control urban malaria in a slum settlement of Delhi, India.
AB  - Operational feasibility and bio-efficacy of alphacypermethrin treated curtains
      was evaluated in slum settlements of Andrews Ganj, New Delhi. Jute curtains
      treated with alphacypermethrin @ 100 mg/m2 were fixed on windows, doors and eves
      before on set of transmission and evaluations were carried out for two years.
      Entomological evaluation revealed that jute curtains treated with
      alphacypermethrin in Slum-I resulted drastic reduction in daytime indoor resting
      mosquitoes such as An. stephensi, Ae. aegypti and Cx. quinquefasciatus.
      Similarly, malaria incidence also reduced in the treated curtain used area when
      compared to that of in untreated curtain and without curtain areas. Bioassay
      tests on An. stephensi and Cx. quinquefasciatus showed that alphacypermethrin
      could produce > 70 per cent mortality up to six months in case of An. stephensi-
      a principal urban malaria vector and hence two rounds of treatment are sufficient
      in an year to protect inhabitants from malaria. The study indicates
      alphacypermethrin treated curtains could curtail malaria transmission in slum
      settlements and is operationally feasible in small houses and is also cost
      effective.

PMID- 14686115
TI  - HLA associations in P. falciparum malaria patients from Mumbai, western India.
AB  - In the present study, HLA associations among the cohort of 171 severe P.
      falciparum malaria patients were compared with that of 101 normal sex, age and
      ethnically matched control samples. All these individuals lived in Mumbai in an
      area of low and seasonal P. falciparum transmission. HLA A, B, DRB1 and DQB1
      antigens were serologically (A and B) and molecularly (DRB and DQB) determined
      using isolated lymphocytes and genomic DNA following the microlymphocytotoxicity
      assay and PCR-SSP techniques. Significant differences were observed between
      patients with malaria and controls in the following groups of alleles: A3, B27,
      B49, DRB1*04, and DRB1*0809 were increased, while A19, A34, B18, B37, and
      DQB1*0203 were decreased. HLA B49 and DRB1*0809 were found to be positively
      associated with the complicated severe malaria patients (OR = 13.88; p < 0.0001).
      HLA A19, B5 and B13 were protective in patients with high parasite index (> 2%).
      These observations revealed the importance of ethnic background, which has to be
      taken into consideration while developing an ideal malaria vaccine. Further, when
      compared to HLA associations of other world populations the present study
      indicates the relative importance of different HLA alleles that may vary in
      different populations.

PMID- 14686116
TI  - Mosquito fauna and breeding habitats of anophelines in Little Andaman Island,
      Andaman and Nicobar Islands, India.
AB  - A total of 37 species of mosquitoes belonging to nine genera--Anopheles, Aedes,
      Armigeres, Culex, Harpagomyia, Mansonia, Orthopodomyia, Toxorhynchites and
      Uranotaenia were collected from Little Andaman Island. Mosquitoes of nine
      Anopheles group of species--An. barbirostris, An. barbumbrosus, An. balabacensis,
      An. insulaeflorum, An. kochi, An. philippinensis, An. roperi, An. sundaicus and
      An. vagus were recorded. An. philippinensis was found to be the most predominant
      species. Species-specific breeding preference and association in various types of
      acquatic habitats have been reported. This is the first record of mosquito fauna
      of Little Andaman Island.

PMID- 14686117
TI  - Study of malaria in a village of lower Myanmar.
AB  - Malaria endemicity in lower Myanmar has been studied to identify the causes for
      the prevalence of malaria in Yeasitkan village of lower Myanmar. Vector
      mosquitoes were collected by mosquito net in cattlesheds and in human dwellings
      (indoor and outdoor) by biting and catching procedure for the identification of
      species, insecticide susceptibility test and sporozoites detection. Larvae of
      mosquitoes were also collected in and around the village for vector
      identification and for breeding sources. Malaria infection in humans was examined
      by blood examination and blood antibody detection by ELISA method. Results showed
      that malaria infection was 43.2% in children under 10 years of age and An. dirus
      and An. minimus were found as main vectors. Total parasite positive rate was
      found to be 41.28% and in this 78.87% were P. falciparum infections and remaining
      18.31% were of P. vivax. Spleen positive rate has been found very high in
      children between 2 and 9 years (52.94%). Study indicates that villages near to
      dam areas are more prone to malaria infection.

PMID- 14686118
TI  - Clinical analysis of malaria cases treated at MGM Hospital, Navi Mumbai.

PMID- 14686119
TI  - Malaria vectors of southern Rajasthan, India.

PMID- 14686120
TI  - ["Post-traumatic stress disorder"--historical aspects of a "modern" psychiatric
      illness in the German language areas].
AB  - Although posttraumatic stress disorder has only recently been admitted into the
      international classification systems, psychological reactions to traumatic
      incidents have been frequently described for well over a hundred years. This
      article provides an overview of mental reactions to a trauma in different
      historical situations. It discusses the "railway spine injuries" of the 19th
      century, victims of accidents in which third party liability could be
      established, and the psychological consequences of the catastrophes that
      characterised the 20th century: World War I, the rule of National Socialism,
      World War II, the expulsion and persecution of political opponents in the former
      GDR. The analysis suggests that the different psychological reactions do not
      describe an identical disorder. It seems that reactions to injuries are mainly
      influenced by the historical and social background.

PMID- 14686121
TI  - [Werner Catel--a protagonist in Nazi "pediatric euthanasia" and his post-war
      career].
AB  - This article deals with the biography of Werner Catel, a German paediatrician and
      protagonist of the Nazi programme for "euthanasia of children". Based on original
      research into recently discovered source materials, two aspects of Catel's life
      are considered. Firstly, Catel's attitude towards "euthanasia" is analysed. This
      analysis is not limited to the period of National Socialism, but focuses also on
      the phase before 1933 and especially on the era after 1945. Secondly, the authors
      explore Catel's academic career. What effects on his career in the later Federal
      Republic of Germany had his exposed role in the Nazi programme for "euthanasia of
      children"? In this context it is also examined how the Christian-Albrechts
      University of Kiel/Germany, which employed Catel until 1960 in a leading
      position, judged the work of its former professor after his death.

PMID- 14686122
TI  - [Artistic sketch of an abnormality from 1683].
AB  - Early-modern drawings of malformations are much less known than the woodcuts and
      etchings of deformed children reproduced and discussed on leaflets or in
      monographs. The present article publishes for the first time a drawing from 1682
      showing the front and rear view of a deformed boy born in Rossla (modern Sachsen
      Anhalt). These illustrations and two surviving written testimonia reveal very
      different attitudes to the malformed child on the part of the various individuals
      involved. Although the information in the sources is not sufficiently precise to
      allow an unequivocal retrospective medical diagnosis of the malformations, two
      possible interpretations are presented.

PMID- 14686123
TI  - Uphill task.

PMID- 14686124
TI  - Run for cover.

PMID- 14686125
TI  - The HSJ interview: Derek Wanless. Sequel opportunities. Interview by Nick
      Edwards.

PMID- 14686126
TI  - Data briefing. Health inequalities.

PMID- 14686127
TI  - Clinical management where medicine meets management. Measure of success.
AB  - Strategic health authorities are driving closer monitoring of local performance
      on public health. Trusts in the South East and North West are pioneering co
      operative work. Acute medical directors and PCT directors of public health are
      working closely together.

PMID- 14686128
TI  - Smoking. Fired up.
AB  - Barnsley and Doncaster are both showing some of the best smoking-cessation rates
      in the country. Doncaster is having particular success with pregnant women and
      prisoners. Working with other agencies and local businesses can bring benefits to
      an overall tobacco strategy.

PMID- 14686129
TI  - Law. Birth rights.

PMID- 14686130
TI  - My brilliant career--clinical governance. Breathe easy.

PMID- 14686131
TI  - HSJ people. Count on it.

PMID- 14686132
TI  - Is low fertility a twenty-first-century demographic crisis?
AB  - Nearly half of the world's population in 2000 lived in countries with fertility
      rates at or below replacement level, and nearly all countries will reach low
      fertility levels in the next two decades. Concerns about low fertility, fertility
      that is well below replacement, are widespread. But there are both persistent
      rationales for having children and institutional adjustments that can make the
      widespread intentions for two children attainable, even in increasingly
      individualistic and egalitarian societies.

PMID- 14686133
TI  - Rethinking the "early" decline of marital fertility in the United States.
AB  - In this article, I rely on new estimates of nineteenth-century mortality and the
      Integrated Public Use Microdata Series to construct new estimates of white
      fertility in the nineteenth-century United States. Unlike previous estimates that
      showed a long-term decline in overall fertility beginning at or before the turn
      of the nineteenth century, the new estimates suggest that U.S. fertility did not
      begin its secular decline until circa 1840. Moreover, new estimates of white
      marital fertility, based on "own-children" methods, suggest that the decline in
      marital fertility did not begin in the nation as a whole until after the Civil
      War (1861-1865).

PMID- 14686134
TI  - Modeling momentum in gradual demographic transitions.
AB  - The analysis of population momentum following a gradual decline in fertility to
      replacement level provides valuable insights into prospects for future population
      growth. Here, we extend recent work in the area by applying a new form of the
      quadratic hyperstable (QH) model, which relates exponentially changing fertility
      to the resultant exponentiated quadratic birth sequence. Modeling gradual
      transitions from an initial stable population to an ultimate stationary
      population indicates that such declines in fertility increase momentum by a
      product of two factors. The first factor is a previously noted continuation of
      stable growth for half the period of decline. The second is a not previously
      appreciated offsetting factor that reflects the interaction between the decline
      in fertility, the changing age pattern of fertility, and the changing age
      composition of the population. Numerical examples using both hypothetical and
      actual populations demonstrate that for declines of any length, the product of
      the two factors yields momentum values that closely agree with the results of
      population projections. The QH model can examine monotonic transitions between
      any two sets of constant vital rates. As a generalization of the fixed-rate
      stable model, it has great potential value in numerous areas of demographic
      analysis.

PMID- 14686135
TI  - Fertility decline and gender bias in northern India.
AB  - Although it is widely acknowledged that the preference for sons is a barrier to a
      decline in fertility, considerable disagreement exists as to what actually
      happens to this preference when fertility declines in a region of low female
      autonomy. By analyzing the data from the National Family Health Survey (NFHS), we
      present evidence from northern India to show that the preference for sons is
      reduced when the ideal family size becomes small, even though it does not
      completely disappear. This finding appears to contradict trends in the juvenile
      sex ratio and the incidence of female feticide that suggest the intensification
      of gender bias. We argue that the anomaly is the result of a diffusion of
      prenatal sex-diagnostic techniques in regions where there is a large unmet demand
      for such methods. Using the NFHS data, we estimate that in northern India, girls
      currently constitute about 60% of the unwanted births and that the elimination of
      unwanted fertility has the potential to raise the sex ratio at birth to 130 boys
      per 100 girls.

PMID- 14686136
TI  - Trends in reproductive behavior among young single women in Colombia and Peru:
      1985-1999.
AB  - Using "calendar" data for single women aged 15-24 from successive Demographic and
      Health Surveys (DHS) conducted in Colombia and Peru during the 1990s, we document
      trends, year by year, in sexual activity, the use of contraceptives, and
      subsequent reproductive outcomes. We provide evidence of the important and
      hitherto largely untapped potential of DHS calendar data to draw complete sexual
      and reproductive profiles when data from various surveys are integrated. Over the
      period 1985-1999, young single women in both Colombia and Peru became sexually
      active at younger ages. The use of contraceptives, especially the use of condoms,
      increased but did not fully offset the rise in sexual activity, and thus the
      incidence of premarital conceptions rose among young single women. In both
      countries, sharp declines occurred in the proportion of premaritally conceived
      births that were reported as being wanted.

PMID- 14686137
TI  - Early origins of the gradient: the relationship between socioeconomic status and
      infant mortality in the United States.
AB  - Although relationships between social conditions and health have been documented
      for centuries, the past few decades have witnessed the emergence of socioeconomic
      gradients in health and mortality in most developed countries. These gradients
      indicate that health improves, although decreasingly so, at higher levels of
      socioeconomic status. To minimize problems with reverse causality, I tested
      competing hypotheses for observed socioeconomic gradients for infant mortality
      outcomes. I found no support for the income-inequality hypothesis and negligible
      support for the occupational-grade hypothesis. The results indicate that absolute
      material conditions are the most important determinants of socioeconomic effects
      on the risk of infant mortality and that while poverty has the most pronounced
      effect on risk, income is decreasingly salutary across the majority of the
      mortality gradient.

PMID- 14686138
TI  - An investigation of racial and ethnic disparities in birth weight in Chicago
      neighborhoods.
AB  - We examine differences in the mean birth weights of infants born to non-Hispanic
      black, non-Hispanic white, and Mexican-origin Hispanic mothers (of any race) in
      Chicago in 1990 using linear regression models with neighborhood fixed effects.
      Our pooled models accounted for 64% of the black-white difference and 57% of the
      black/Mexican-origin Hispanic difference. Differences in the relationship between
      measured characteristics and birth weight accounted for around half the birth
      weight gap between non-Hispanic black and other infants. Efforts to close this
      gap must go beyond programs that aim to reduce the level of risk factors among
      black women to address the causes of differences in the effects of risk factors.

PMID- 14686139
TI  - Verification of the ages of supercentenarians in the United States: results of a
      matching study.
AB  - Unprecedented declines in mortality among the very old have led to the emergence
      of "true" supercentenarians (persons aged 110 and over). The ages of these
      individuals have been well-documented in European countries with a history of
      birth registration, but have not been systematically studied in the United
      States, which lacks similar documentation and where the inaccuracy of age
      reporting has been an issue. To verify age, we linked records from the Social
      Security Administration for close to 700 individuals who died from 1980 to 1999
      purportedly at ages 110 and older to records of the U.S. censuses of 1880 and
      1900, conducted when these individuals were children. This group was a residual
      group from an earlier file that was reduced by the SSA after data checks that
      eliminated incorrect records. The results of the matched records for the residual
      file indicate that over 90% of the whites were accurately reported as
      supercentenarians, but only half of the blacks appeared to have attained age 110.
      The verification of age shows that the United States has more "true"
      supercentenarians than do other nations.

PMID- 14686140
TI  - An evaluation of population projections by age.
AB  - A number of studies have evaluated the accuracy of projections of the size of the
      total population, but few have considered the accuracy of projections by age
      group. For many purposes, however, the relevant variable is the population of a
      particular age group, rather than the population as a whole. We investigated the
      precision and bias of a variety of age-group projections at the national and
      state levels in the United States and for counties in Florida. We also compared
      the accuracy of state and county projections that were derived from full-blown
      applications of the cohort-component method with the accuracy of projections that
      were derived from a simpler, less data-intensive version of the method. We found
      that age-group error patterns are different for national projections than for
      subnational projections; that errors are substantially larger for some age groups
      than for others; that differences in errors among age groups decline as the
      projection horizon becomes longer; and that differences in methodological
      complexity have no consistent impact on the precision and bias of age-group
      projections.

PMID- 14686141
TI  - The academic trajectories of immigrant youths: analysis within and across
      cohorts.
AB  - Two nationally representative cohorts--from the National Educational Longitudinal
      Study (NELS) and High School and Beyond (HSB)--were used to examine the effects
      of generation and duration of residence on students' performance on standardized
      tests over a two-year period. In multivariate models, generational status
      predicts variation in students' performance on baseline (sophomore) tests, with
      effects stronger for the later age cohort (NELS) than for the earlier age cohort
      (HSB). With regard to the trajectory of achievement, generational status has a
      greatly reduced role for both cohorts. The best predictors of the trajectory of
      achievement are not those that are based on nativity per se, but those that
      reflect the social environment experienced in the United States (i.e., ethnicity
      and family's socioeconomic status).

PMID- 14686142
TI  - [Low viscosity composites as materials for orthodontic bonding].
AB  - A new type of composite materials, referred to as low viscosity composites, has
      been introduced onto the dental market. Little has been published yet concerning
      the biological and mechanical properties of these new materials, and the
      practitioner has to rely on the information, provided by the manufacturer. The
      low viscosity composites are hybrid composites, with a decreased amount of filler
      particles. This results in a lower viscosity, which makes these materials more
      appropriate in certain situations. Since the filler loading of these materials is
      decreased, one could expect inferior mechanical properties, compared to the
      conventional and hybrid composites. Therefore, the indications for using low
      viscosity composites are limited. In this article we propose to use low viscosity
      composites for the bonding of lingual retainers and implant-borne transpalatal
      arches. The explicit feature of flow, is very attractive for these indications,
      because a minimum of finishing is needed, when a low viscosity composite is used
      in these situations. Since there is no direct occlusal bite force put on the
      composite, the fact that the mechanical properties of a low viscosity composite
      could be inferior to those of a conventional composite, can be disregarded. A
      protocol for fixing lingual retainers and implant-borne transpalatal arches is
      proposed in the article, with other tips, concerning the fabrication of the
      retainers themselves.

PMID- 14686143
TI  - [The armamentarium of the periodontologist].
AB  - The aim of this article is to describe the products available to the periodontist
      for the regeneration of bone and periodontal tissues. According to distinct
      biological mechanisms responsible for their regenerative potential, these
      products can be classified upon three groups: bone substitutes, membranes and
      enamel matrix proteins. The rationale for trying to regenerate the periodontium
      after the initial non-surgical phase of the periodontal treatment is discussed.
      The indications of these products according to their biological principles are
      described as well as their limitations. The safety of the products of allogenic
      origin is discussed.

PMID- 14686144
TI  - [Toward an ideal composite: is every modification a synonym for improvement?].
AB  - Composite materials have gained widespread acceptance as anterior and posterior
      direct restorations. The past decades have been marked by a rapid development of
      new adhesive techniques and frequent changes of products and their presentation.
      Several of the new features have been shown to be of less clinical importance
      than initially claimed, others still await long-term clinical studies. If used
      according to indications and guidelines, composite restorations can achieve a
      satisfactory life-span. However, user factors determine a great part of the
      individual success. Clinical evaluation by long-term controlled studies is less
      frequent than in-vitro studies. Between the initiation of a study and the
      publication of the results the products more often than not have been replaced.

PMID- 14686145
TI  - [Importance of cell cultures in biocompatible dental materials research].
AB  - The need for biocompatible materials implies the necessity of toxicity testing.
      The toxicity of a dental material can be evaluated by in vitro tests, by animal
      experimentation including usage tests, and by clinical studies in humans. In
      vitro studies are mainly performed to evaluate the cytotoxicity (cell damage) or
      the genotoxicity (specific DNA damage or chromosomal aberration) of a dental
      material. Cell or tissue cultures play an important role because they allow a
      maximum standardization. This paper describes their application and
      interpretation of results in biocompatibility tests.

PMID- 14686147
TI  - [Christine Malevre condemned on appeal to twelve years in prison].

PMID- 14686153
TI  - [Herpes, a disease to track].

PMID- 14686155
TI  - [Evolution of podiatric care in the diabetic patient].

PMID- 14686156
TI  - [Clinical research nurses, the cornerstones of well-conducted clinical trials].

PMID- 14686157
TI  - [Nurse-patient relations, more than a simple practice technique].

PMID- 14686158
TI  - [The patient's logic or the right to differ].

PMID- 14686159
TI  - [Disease, suffering and nursing care].

PMID- 14686160
TI  - [Understanding the care situation and producing an adequate therapeutic response,
      two fundamental axes of the nurse-patient relationship].

PMID- 14686161
TI  - [Collection, re-collection, giving, receiving...].

PMID- 14686162
TI  - [The nursing relationship, the nurse's viewpoint and the patient's viewpoint].

PMID- 14686163
TI  - [Nursing care relationship, patient autonomy and therapeutic education].

PMID- 14686165
TI  - [Tell the truth to patients, a varied experience].

PMID- 14686164
TI  - [An "expanded" nurse-patient relationship guaranteed by experience and
      professionalism].

PMID- 14686166
TI  - [Information is at the heart of the nursing relationship].

PMID- 14686167
TI  - [Taking care of caring. Interview by Bernadette Fabregas].

PMID- 14686168
TI  - [Best use of drugs. B. Antibiotic usage 13/ Gastrointestinal infections (2/2)].

PMID- 14686169
TI  - [II--Nursing relationships. 1/10 persons who manifest anxiety or fear].

PMID- 14686171
TI  - [The Clery-Melin report presents its action plan for reorganizing psychiatry and
      mental health].

PMID- 14686172
TI  - [Study of health professionals' perception of quality].

PMID- 14686173
TI  - [Return of the education for nurses practising in psychiatry].

PMID- 14686174
TI  - [Qualitative dimensions of long-term hospitalization in psychiatry].

PMID- 14686175
TI  - [Persons regularly followed for mental disorders].

PMID- 14686176
TI  - [Social representations of mental illness. For another view of mental illness].

PMID- 14686177
TI  - [Representations of mental illness during the ages in the western world].

PMID- 14686178
TI  - [The case of the "king's fool"].

PMID- 14686179
TI  - [Mental illness in the country].

PMID- 14686180
TI  - [Changing our attitude to care better].

PMID- 14686181
TI  - [Do social perceptions influence the choice to practise in psychiatry? Interview
      by Armel Rivallan].

PMID- 14686182
TI  - [Stigmatization or recognition, a question of political will].

PMID- 14686183
TI  - [Self esteem in social perceptions].

PMID- 14686184
TI  - [Therapeutic interventions, a question of logic?].

PMID- 14686185
TI  - [Nursing records and quality of care. Interview by Armel Rivallan].

PMID- 14686186
TI  - The future of the dental profession: a personal perspective.
AB  - Future needs and demands for oral healthcare will, it is suggested, largely
      determine the forum, function and size of the dental profession. With the coming
      of age of the dental team and the development of an ever-increasing range of new
      therapies, materials, procedures and devices, new organizational systems will be
      needed to support education and training and subsequent lifelong learning. It is
      concluded that it is time for the dental team and its regulation to move on.
      Subject to the profession embracing the future, the years ahead promise to bring
      many new, exciting opportunities and challenges.

PMID- 14686187
TI  - 30 years of preventive dentistry--and 30 years into the future.
AB  - Preventive dentistry has had a major impact on the prevalence of dental caries
      and, to a lesser extent, periodontal disease since the 1970s. It should continue
      to have a positive effect on the oral health of the community in the future. The
      factors behind improvements seen in oral health are many and varied but include
      changes in public health policy, technology and commercial decisions made in the
      industrial sector. As oral health has improved, and tooth retention increased,
      the focus of preventive dentistry has widened to include all population groups,
      increasingly including older adults, and to include a wider range of disorders.
      The major issues relevant to preventive dentistry which have occurred over the
      last 30 years are discussed. The authors will speculate on the impact that the
      prevention of oral disease might have over the next 30 years.

PMID- 14686188
TI  - From I don't care to customer care. An evolution in patient expectation.
AB  - This paper explores the way that the delivery of dental care has changed over the
      past three decades. Comparisons are made between dentistry and other business
      fields to show how the profession has moved in line with shifts in societal
      attitudes.

PMID- 14686189
TI  - From extension for prevention to prevention of extension: (minimal intervention
      dentistry).
AB  - Minimal intervention techniques cause less destruction of tooth substance than
      conventional techniques, with reduced risk of tooth fracture and pulpal problems.
      This article describes conventional cavity designs and discusses currently
      available minimal intervention techniques.

PMID- 14686190
TI  - Paediatric dentistry in the new millennium: 5. Clinical prevention: the role of
      the general dental practitioner.
AB  - Prevention of caries underpins all dental care provided to children. This paper
      reviews the scientific basis of current techniques for dental prevention. It
      provides guidelines for the identification of children who are at high and low
      risk and considers the most appropriate preventive strategies for these children.

PMID- 14686191
TI  - Occlusion: 3. Articulators and related instruments.
AB  - Dental articulators are instruments that reproduce jaw movements to varying
      degrees of accuracy. This article aims to give an overview of the various types
      of articulator and describe their applications and limitations.

PMID- 14686192
TI  - Crowns revisited.
AB  - This paper overviews recent changes to making crowns. For the most part it
      presents clinically relevant information using examples where necessary. The
      paper will act as a useful reminder for the techniques involved with crown
      preparations and the choices of materials available.

PMID- 14686193
TI  - Physical signs for the general dental practitioner. Case 9. Behcet's disease.

PMID- 14686194
TI  - New directions.

PMID- 14686195
TI  - Guest eye view.

PMID- 14686196
TI  - A night with Techmed 1.

PMID- 14686197
TI  - Consultant nurses: the next generation.

PMID- 14686198
TI  - Smoke inhalation: assessing and managing patients.

PMID- 14686199
TI  - Acute severe asthma in pregnancy.

PMID- 14686200
TI  - Working together for child protection in A&E.

PMID- 14686201
TI  - [Occupational medicine in Kazakhstan].

PMID- 14686202
TI  - [Biochemical and hormonal characteristics of workers engaged into mining
      manganese-containing ores].
AB  - Medical examination of workers engaged into digging of manganous ores proved
      correlation between nitrogen oxide level in expired air and rhinocytogram
      parameters, revealed sensitivity of cardiovascular and neuroendocrine systems to
      polymetallic dust.

PMID- 14686203
TI  - [Influence of occupational factors on combined vertebrogenous disorders and
      vibration disease in miners (review of literature)].

PMID- 14686204
TI  - [Role of ultrasound diagnostics in evaluating of adaptational changes in heart in
      miners].
AB  - Ultrasound examination of cardiovascular system covered apparently healthy coal
      miners with consideration of service under exposure to coal rock dust. Findings
      are increased blood velocity, higher pressure gradient and average pulmonary
      artery pressure, thicker front wall of right ventricle.

PMID- 14686205
TI  - [Diagnostic criteria of pulmonary hypertension among chronic dust bronchitis
      patients].
AB  - The examination covered chronic dust bronchitis patients in whom pulmonary
      hypertension was staged with echocardiographic criteria through a complex of
      revealed structural, functional and hemodynamic disorders.

PMID- 14686206
TI  - [Psychofunctional state of remote education students].
AB  - The authors present data concerning examination of psychofunctional state of
      students who receive remote education during various years. Information load of
      nonconventional education is associated with reorganization of central regulatory
      mechanisms and changes in cognitive brain functions.

PMID- 14686207
TI  - [Environmental pollution with heavy metals at carrier rockets fall areas].
AB  - Based on hygienic monitoring, the authors evaluated environmental pollution with
      heavy metals at carrier rockets fall places and determined actual chemical load
      on environment.

PMID- 14686208
TI  - [Influence of ecologic situation on female reproductive health and newborn
      state].
AB  - The authors studied reproductivity in females who reside in industrial region,
      but are not subjected to occupational hazards. The work also covered studies of
      newborn state, analysis of demographic parameters, causes of early neonatal and
      infant mortality, level and spectrum of congenital diseases.

PMID- 14686209
TI  - [Evaluation of hormonal state in workers in rubber manufacturing industry].

PMID- 14686210
TI  - [Possibility of excretion of fine-dispersed dust particles through
      gastrointestinal tract].

PMID- 14686211
TI  - [Health status of miners and students mastering miner professions].

PMID- 14686212
TI  - [Phosphoinositides in pulmonary, hepatic tissues, and blood under exposure to
      industrial dust with higher content of cooper].

PMID- 14686214
TI  - Senate mulls oversight of pharmacy compounding.

PMID- 14686213
TI  - [Contemporary methods for early diagnosis of bronchial obstruction syndrome with
      pulmonary dust pathology].

PMID- 14686215
TI  - ASHP, other groups, advise FDA about solving counterfeit drug problems.

PMID- 14686216
TI  - Consumer-directed pharmacy benefits coming next year.

PMID- 14686217
TI  - FDA examines direct-to-consumer advertising data.

PMID- 14686218
TI  - Recent changes to FDA-approved labeling.

PMID- 14686219
TI  - New drugs and dosage forms.

PMID- 14686220
TI  - Aripiprazole.
AB  - The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug
      interactions, and dosage and administration of aripiprazole are discussed.
      Aripiprazole is a third-generation antipsychotic agent indicated for use in the
      treatment of schizophrenia. Unlike other antipsychotics, aripiprazole
      demonstrates mixed D2 and serotonin (5-HT1A) receptor agonist-antagonist activity
      that is hypothesized to improve schlzophrenia's positive and negative symptoms;
      the drug has been referred to as a dopamine-serotonin stabilizer. Aripiprazole is
      well absorbed, with peak plasma concentrations occurring within three to five
      hours after administration. The oral availability is 87%. The mean elimination
      half-life is about 75 hours for aripiprazole and 94 hours for its active
      metabolite. In controlled, randomized, multicenter trials, aripiprazole has
      demonstrated efficacy in the treatment of schizophrenia comparable to that of
      haloperidol and superior to placebo. In a single clinical trial, aripiprazole was
      superior to placebo in the treatment of acute mania. The most frequent adverse
      effects are headache, anxiety, insomnia, nausea, vomiting, and lightheadedness.
      Because aripiprazole is a substrate of both cytochrome P-450 isoenzymes 3A4 and
      2D6, there is a potential for other drugs to affect its metabolism. The
      recommended starting dosage is 10 or 15 mg daily, preferably administered with
      meals. Aripiprazole offers an alternative to second-generation antipsychotic
      agents in the treatment of schizophrenia.

PMID- 14686221
TI  - Expert consensus-based medication-use evaluation criteria for atypical
      antipsychotic drugs.
AB  - Medication-use criteria for the appropriate use of atypical antipsychotics were
      developed through a national consensus process utilizing an expert panel. A
      written survey was prepared which asked for opinions about options for
      psychopharmacologic interventions with seven antipsychotic drugs or categories
      (clozapine, olanzapine, quetiapine, risperidone, ziprasidone, long-acting
      intramuscular decanoate ester preparations of conventional antipsychotics, and
      oral conventional antipsychotics) in 19 specific clinical situations. The survey
      was sent to 50 psychiatrists and psychiatric pharmacist specialists, 42 (84%) of
      whom completed the survey. The survey was formatted as a grid with rows listing
      various clinical situations and columns itemizing the various antipsychotic
      medications relevant to the situations. Responses were scored using a 9-point
      scale for rating the level of medical review required for any given decision.
      Consensus on each option was defined as a nonrandom distribution of scores by a
      chi-square goodness-of-fit test. Consensus was reached for 1179 of the 1230 items
      reviewed. Use of clozapine as a first-line therapy warranted prospective or
      mandated review for all diagnoses. Use of nonclozapine atypical agents for
      schizophrenia and schizoaffective and delusional disorders was judged to be the
      standard of care. Oral conventional antipsychotic agents were not considered the
      standard of care for any indication. Combination antipsychotic treatment always
      warranted at least concurrent review. Continued concerns about the use of
      ziprasidone and its cardiac effects were apparent. This study demonstrated the
      utility of a consensus-based process in addressing issues and practices not
      adequately addressed in the scientific literature.

PMID- 14686222
TI  - Dosage of beta-adrenergic blockers after myocardial infarction.
AB  - Dosages of beta-adrenergic blockers prescribed after myocardial infarction (MI)
      in a Veterans Affairs medical center were reviewed to determine if dosages were
      adjusted to target dosages used in clinical trials. The medical records of all
      patients with a discharge diagnosis of MI were reviewed. The target dosage,
      selected from major clinical trials, was atenolol 100 mg/day p.o., metoprolol
      tartrate 200 mg/day p.o., or propranolol 180-240 mg/day p.o. A systolic blood
      pressure of < or = 100 mm Hg and pulse rate of < or = 50 beats/min were defined
      as the clinical markers of the maximum tolerated beta-blocker dosage. A discharge
      diagnosis of MI was identified in 396 patients between January 1999 and December
      2000, and 106 patients met the inclusion criteria. The patients had a mean +/-
      S.D. age of 66.3 +/- 10.7 years, 98% were men, and all received either atenolol
      or metoprolol. The mean +/- S.D. systolic and diastolic blood pressure and pulse
      rate on admission were 135 +/- 30 and 75 +/- 18 mm Hg and 80 +/- 20 beats/min,
      respectively. The mean +/- S.D. dosages for atenolol and metoprolol were 54 +/-
      39 and 90 +/- 77 mg/day at the time of discharge, 54 +/- 38 and 95 +/- 81 mg/day
      at 6 months after discharge, and 53 +/- 40 and 82 +/- 80 mg/day at 12 months,
      respectively. Only 15% of the patients reached the target dosage, as defined in
      clinical trials, of a beta-blocker. No reason for maintaining the beta-blocker
      dosage was documented for 65% of the patients. Beta-blockers were prescribed
      frequently after MI but usually were not used at dosages that matched those in
      clinical trials.

PMID- 14686223
TI  - Delivery of multimedia educational presentations via streaming media.

PMID- 14686224
TI  - Fluconazole- and levofloxacin-induced torsades de pointes in an intensive care
      unit patient.
AB  - Patients initiated on fluconazole and levofloxacin should be closely monitored
      for QTc-interval prolongation. While there have been published reports of
      fluconazole and levofloxacin causing QTc-interval prolongation when given alone,
      coadministration of these two agents may further increase this risk. This case
      describes an episode of TdP in which levofloxacin and fluconazole were likely
      significant factors. QT prolongation was present at baseline prior to drug
      initiation (QTc = 454-505 ms) and levofloxacin resulted in further prolongation
      (QTc = 480-536 ms). After two days of therapy with fluconazole, overlapping with
      levofloxacin, the patient had an episode of PMVT with syncope, and progressive QT
      prolongation was evident (QTc = 554 ms). Only mild hypokalemia (potassium
      concentration = 3.6 meq/L) was present, and not additional etiologies for TdP
      were identified. Levofloxacin and fluconazole were discontinued and no further
      PMVT was observed, but the QT interval did not return to normal until after an
      additional 11 days (QTc = 436 ms). As in many cases of TdP, multiple factors were
      involved. Renal failure, drug dosing, mild hypokalemia, and a baseline abnormal
      QT interval potentiated the role of levofloxacin and fluconazole in the
      development of TdP. We recommend that neither drug be used alone or in
      combination when there is baseline QT prolongation. We also recommend that
      concomitant use of these agents be avoided when possible. If combination therapy
      is required, caution is warranted, particularly in patients with risk factors for
      QT prolongation. Specific attention should be given to drug dosing, interactions,
      electrolytes, and ECG monitoring.

PMID- 14686225
TI  - Health in a hand basket? Pursuing your profession through a challenging, changing
      landscape.

PMID- 14686226
TI  - Medical education and communication companies.

PMID- 14686227
TI  - Prevention and treatment of cytomegalovirus disease in solid organ transplant
      recipients: the clinical and economic impact of evolving strategies.
      Introduction.

PMID- 14686228
TI  - Costs and consequences of cytomegalovirus disease.
AB  - The impact of prophylactic oral ganciclovir therapy on the incidence of
      cytomegalovirus (CMV) disease, patient and graft survival, and costs in patients
      receiving kidney and liver transplants is described. CMV disease is a common
      cause of morbidity and mortality in solid organ transplant recipients unless
      prophylactic drug therapy is used. Prophylactic oral ganciclovir therapy reduces
      the incidence of CMV disease in kidney and liver transplant recipients. It is
      more effective for recipients who are seronegative before the transplant and
      receive organs from seronegative (D-/R-) donors than in seronegative recipients
      of organs from seropositive (D+/R-) donors. CMV disease remains a problem in the
      latter. CMV disease increases the risk of graft failure, which decreases the
      likelihood of patient survival. The extent of matching of the DR subregion of the
      human leukocyte antigen complex in the donor and recipient may affect graft
      survival in patients with CMV disease. Graft failure is costly and should be
      considered in economic analyses of CMV prophylaxis regimens because of the
      potential impact of prophylaxis on CMV disease. The use of oral ganciclovir for
      CMV prophylaxis has reduced the incidence of CMV disease in kidney and liver
      transplant recipients.

PMID- 14686229
TI  - Cost advantages of oral drug therapy for managing cytomegalovirus disease.
AB  - Cost advantages of the oral route of drug therapy administration over the
      intravenous route for managing cytomegalovirus (CMV) disease are described. The
      overall costs usually are lower for the oral route of administration than for the
      intravenous route, although the cost to the patient depends on insurance
      coverage. Other advantages of the oral route include greater safety and
      convenience, which may improve patient adherence and quality of life. In patients
      with acquired immunodeficiency syndrome (AIDS), the use of oral ganciclovir
      instead of intravenous ganciclovir to treat the maintenance phase of CMV
      retinitis reduced the incidence of neutropenia and sepsis, outpatient and
      inpatient resource use, and costs. Oral therapy also improved patient quality of
      life. A cost-effectiveness model for liver transplant recipients found that CMV
      prophylaxis is warranted for all patients, ganciclovir is preferred over CMV
      immune globulin i.v. and oral acyclovir for prophylaxis, and the oral route of
      administration is more cost-effective than the intravenous route for ganciclovir.
      Valganciclovir, the oral prodrug of ganciclovir, was not included in this model.
      Oral maintenance therapy is usually cost-effective, safer, and more convenient
      than intravenous therapy in the management of CMV.

PMID- 14686230
TI  - New prophylactic treatment strategy for cytomegalovirus disease.
AB  - The pharmacology, pharmacokinetics, safety, and efficacy of valganciclovir, an
      oral prodrug for ganciclovir, used to prevent cytomegalovirus (CMV) disease in
      solid organ transplant recipients are described. Valganciclovir was developed to
      overcome the disadvantages associated with ganciclovir, which include low oral
      bioavailability, limited efficacy because of the development of viral resistance,
      and the need for frequent administration, which can adversely affect patient
      adherence. Valganciclovir is rapidly converted to ganciclovir; systemic exposure
      to the parent drug is low and short in duration. The oral bioavailability of
      ganciclovir from valganciclovir is 10 times higher than that from the original
      ganciclovir formulation. Food increases the oral bioavailability of
      valganciclovir. In a four-way, randomized, crossover pharmacokinetic study of 28
      liver transplant recipients, single doses of valganciclovir 900 mg and
      intravenous ganciclovir 5 mg/kg resulted in a similar ganciclovir systemic
      exposure. The systemic exposure was proportionately lower with a single 450-mg
      dose of valganciclovir but similar to that of oral ganciclovir 3 g administered
      in three divided doses. In the recent multicenter, randomized, double-blind,
      double-dummy PV16000 trial in 364 solid organ transplant recipients at high risk
      for CMV disease (i.e., CMV-negative recipients of CMV-positive donor organs),
      valganciclovir 900 mg once daily was as effective in preventing CMV-disease as
      oral ganciclovir 1 g three times daily. Resistance was reported with ganciclovir
      but not with valganciclovir. Both drugs were well tolerated.

PMID- 14686231
TI  - Formulary considerations for drugs used to prevent cytomegalovirus disease.
AB  - Four types of therapeutic strategies for managing cytomegalovirus (CMV) in solid
      organ transplant recipients, the mechanisms of action and efficacy of drugs used
      for prophylaxis, and the criteria for evaluating drugs for inclusion in a
      formulary are described. Universal and selective prophylaxis are simple to
      implement and effective for CMV prophylaxis, but they are costly and patient
      nonadherence and viral resistance can develop. Preemptive therapy may cause less
      resistance and cost less, but it is more complex and associated with a higher
      incidence of infection, which may have no effect on secondary effects from CMV
      infection, and higher recurrence of disease than prophylactic therapy. Treatment
      of active disease may be less costly for the drug than other approaches, but
      intravenous access is required and the rates of infection recurrence and
      mortality are higher compared with prophylaxis and preemptive therapy. Criteria
      for deciding which CMV prophylactic drugs to include in a formulary include
      efficacy, safety, convenience, and cost. CMV immune globulin i.v. is costly and
      exhibits reduced efficacy when used alone in patients at high risk for CMV
      disease. Intravenous ganciclovir is effective, but it is costly because of
      infusion costs. Intravenous drug therapies are inconvenient and associated with a
      risk of bacterial and fungal infection. Oral acyclovir is safe to use and
      inexpensive (since a genetic exists), but it has poor efficacy and is
      inconvenient because of the need for four large daily doses. Valacyclovir is more
      convenient and with similar safety and probably better efficacy than acyclovir,
      but it is more costly. Oral ganciclovir and oral valganciclovir have similar
      safety and costs, with greater efficacy than acyclovir. The single daily dose and
      lack of resistance to valganciclovir are advantages over oral ganciclovir, which
      requires three daily doses and can result in the development of resistance.

PMID- 14686232
TI  - Failure to act when you know error on meds risks life.

PMID- 14686233
TI  - Deplorable ICU nursing results in $2.4 million judgment. Case on point: Mobile
      Infirmary Medical Center v. Hodgen, 2003 WL 22463340 so.2d--AL.

PMID- 14686234
TI  - GA: nurse injured on non-scheduled lunch break: was nurse eligible for workers'
      compensation?

PMID- 14686235
TI  - LA: comp. awarded to nurse injured on job: nurse teaches school & entitled to
      differential only.

PMID- 14686236
TI  - Sexual harassment of nurses by physician is not tolerated! Case on point:
      Maheshwari v. Vista Hospital System, Inc., 2003 WL 22079563--CA.

PMID- 14686237
TI  - Physician executive compensation continues to rise despite recession. Median pay
      up 7 percent to $225,000 over last 2 years.

PMID- 14686238
TI  - Working with Generation X physicians.
AB  - Learn ways to integrate Generation X physicians into your hospital or practice.
      Discover how their career goals differ from the earlier generation's and find out
      how health care organizations can help meet those goals.

PMID- 14686239
TI  - Managing different generations requires new skills, insightful leadership.

PMID- 14686240
TI  - Recruiting GenX physicians.
AB  - Making the right hiring decisions with GenX physicians can be a challenge. Learn
      some strategies for recruiting and retaining young practitioners.

PMID- 14686241
TI  - Mission to Africa. Physician executive faces Third-World perils bringing first
      rate care to Africa.

PMID- 14686242
TI  - Are you ready for that promotion?

PMID- 14686243
TI  - The Joint Commission is coming! The Joint Commission is coming!

PMID- 14686244
TI  - The art of making change happen.

PMID- 14686245
TI  - CPOE is much more than computers.
AB  - A prominent hospital in Pennsylvania turned to CPOE to help reduce medical errors
      and improve patient care. Learn what steps hospital officials took to establish a
      successful CPOE system.

PMID- 14686246
TI  - The physician executive and patient satisfaction.

PMID- 14686247
TI  - Trust your gut instincts ... or not!

PMID- 14686248
TI  - From physician leader to corporate physician.

PMID- 14686249
TI  - Something old, something new: harnessing technology of the future.

PMID- 14686250
TI  - An insider's look at recruiters and recruiting.

PMID- 14686251
TI  - Process redesign. Part 1: Process selection.

PMID- 14686252
TI  - [HIV/AIDS positive patients in surgery. Part I: Epidemiologic situation].
AB  - INTRODUCTION AND MATERIAL: The paper is mostly based on materials and experience
      of the first author, who took part in an expert action, together with an
      international team of surgeons, treated more than 6000 HIV-positive patients in
      Botswana and performed more than 3,200 interventions himself. The co-authors
      corrected the African experience by a brief survey of experience in this country
      and reviewed the presently valid legislation. METHODS: The first two parts deal
      with literature knowledge on HIV/AIDS and confront it with the author's
      experience over three years of his expert stay in a hospital in Gabarone. The
      first part deal with epidemiological situation in the place of study and the
      second part analyzes in a general aspect the problems of surgical intervention in
      HIV-positive patients and the occupational risk. This part also includes a
      corresponding description of conditions in the Czech Republic including Czech
      legislation. The third, principal, part of the contribution is a prospective
      study where the author, under limited local conditions, investigated 3,200 HIV
      positive patients undergoing surgery. The relation between HIC and tuberculosis
      is also analyzed from various other minor aspects and there are mainly the levels
      of CD4+ T lymphocytes followed from the standpoint of course of therapy and
      prognosis of the patients. The fourth part of the paper describes briefly twelve
      cases confirming and illustrating the results. RESULTS: HIC-positive individuals
      with the CD4 value below 200/mm3 represent the critically endangered patients.
      The values between 200 and 499 represent a distinct risk, which may be overcome,
      and values between 500 and 799 represent a minimum risk, whereas the value over
      800 is exceptionally favorable. Tuberculosis is a very frequent opportune
      infection in African conditions (over 53% in the cohort under study), but rather
      than to influence the prognosis itself it act in relation to the values of CD4+ T
      lymphocytes. The main risk for surgical patients related to decreased immunity is
      not due to complications in the wounds and anastomoses, but in severe opportune
      infections. CONCLUSIONS: This most comprehensive surgical survey on HIV/AIDS,
      worked out by Czech authors, is very well applicable in conditions of the Czech
      Republic.

PMID- 14686253
TI  - [HIV/AIDS positive patients in surgery. Part II: Surgery and the HIV-positive
      patient, methods of occupational protection in health care workers. Legislation].

PMID- 14686254
TI  - [Peroperative diagnostic methods during esophageal achalasia surgery. Initial
      experience].
AB  - AIM OF THE STUDY: The authors present their first experience with the application
      of esophageal manometry during the operation on achalasia of esophagus. The
      completeness of performed myotomy is evaluated on the basis of decreased pressure
      in the region of lower esophageal sphincter (LES). METHODS: Stationary pull
      through four-channel manometry was performed twice during the operation: before
      the application of capnoperitoneum to localize LES with evaluation of its length
      and tonus and after the myotomy was performed after capnoperitoneum was abolished
      to verify sufficient extent of myotomy. The subsequent endoscopic control was
      used to exclude damage of esophagus mucous membrane. RESULTS: In the period of
      one year during 2002/2003 the authors operated on four patients with achalasia,
      when manometry was used for peroperative localization of LES and evaluation of
      the extent of myotomy. The peroperation manometry demonstrated decreased tonus of
      LES (the mean 42.06 mmHg before myotomia and the mean 20.03 mmHg after myotomia)
      and in one case the finding resulted in necessary extension of myotomia.
      CONCLUSIONS: Based on our preliminary experience with peroperation manometry in
      operations on achalasia of esophagus it may be stated that it is a useful method
      for objectivization of the completeness of myotomy, which does not significantly
      prolong the period of operation. It contrast, it makes it possible to respond to
      lasting hypertonic area in LES subjected to myotomy, which may be the cause of
      lasting complaints of patients after the operation.

PMID- 14686255
TI  - [What are indications for hepatic resection in metastases?].
AB  - INTRODUCTION: In the last 20 years the resection of liver metastases became the
      method of choice in the therapy of malignant tumors, particularly of colorectal
      cancer. The study was aimed at evaluating indication criteria and operation
      tactics in liver metastases resection. MATERIALS AND METHODS: The authors
      retrospectively analyzed a group of 154 patients subjected to liver resection for
      metastases, having been operated on since 1980 to May 2003. The preoperative
      indication procedure included a) imaging examination of the liver (CT, NMR, DSA-
      radiological staging), b) evaluation of tolerance to liver resection to liver
      resection (ASA, hem-coagulation tests, liver tests, nutritional state), c)
      examination to exclude the occurrence of extrahepatic tumor (imaging and
      endoscopic methods). In addition to peroperative examination (surgical staging)
      and selective vascular exclusion in anatomical resection, the standard operation
      procedure was supplemented in the last five years with transaction of the liver
      by means of the harmonic scalpel. From the total number, metastases of colorectal
      cancer were resected in 116 patients, in 20 gall bladder cancers, in 6 stomach
      cancers, in 4 breast cancers, in three carcinoids of colon and intestine and in
      two kidney cancers. Individual patients suffering from metastases of adrenal
      cancer, pancreas cancer and melanoma, respectively, were also operated on. More
      extensive anatomical resections were performed in 44 patients, segmentectomy was
      made in 43 subjects and non-anatomical wedge-shaped resections in 67 individuals.
      RESULTS: Postoperative complications occurred in 15 (9.8%) patients (subphrenic
      hematoma, abscess, cholascos, fluidothorax, pulmonary or early infection). Two
      patients died within 30 days (1.3%) for hemorrhagic shock due to bleeding from
      duodenal ulcer and from hepatorenal failure). CONCLUSION: 1. Liver resection is
      indicated is resectable metastases of colorectal cancer. 2. The resection exerts
      a therapeutic effect in non-colorectal metastases in neuroendocrine tumors, tumor
      of uropoetic and genital system, breast cancer, sarcoma and melanoma. 3. The
      preoperative diagnosis should include: a) imaging examination of the liver and
      the site of primary tumor and possible occurrence of other metastases, b)
      determination of tolerance to liver resection. 4. The operation tactics includes
      the peroperative evaluation of operability, radical resection of metastases with
      1 cm border of unaffected liver tissue and procedures leading to diminished blood
      loss and biliary stasis. 5. Anatomical resection is indicated in larger
      metastases affecting segments of one lobe. Non-anatomical wedge-shaped resection
      is aimed at removal of peripheral foci.

PMID- 14686256
TI  - [Surgical treatment of peritoneal adhesions--personal experience].
AB  - Peritoneal adhesions develop virtually in all abdominal operations. In about 30%
      they cause subsequent complications, especially disorders of intestinal passage,
      spasms and female infertility. The authors describe their first experience with
      implantation of resorptive foil Seprafilm and recommend general scheme for the
      approach in prevention and subsequent solution of the problem of adhesion-lysis.

PMID- 14686257
TI  - [Appendicitis and salmonellosis, a coincidence or etiopathogenically related?].
AB  - The authors describe a rare case report of a female patient with acute
      appendicitis, where the course was masked by gastroenteritis complicated with
      sepsis with a simultaneous course of imported infection with Salmonella type C
      (Kentucky). The attention is drawn to the fact that even such frequent abdominal
      emergency as appendicitis is, may cause diagnostic hesitations, if it is masked
      by a simultaneous alimentary infection. In spite of the application of a broad
      scope of examination methods a final decision of indication for laparotomy
      depends on clinical findings of the examining surgeon.

PMID- 14686258
TI  - [Asynchronous occurrence of three neoplastic diseases: chronic B-cell lymphatic
      leukemia, renal carcinoma and prostatic adenocarcinoma].
AB  - Authors present a case of three asynchronous malignancies in man working life
      long in chemical industry. Course of diseases and their treatment are described:
      B chronic lymphatic leukaemia (B-CLL) (age of 55), conventional clear cell renal
      carcinoma (CRCC) (age of 61) and adenocarcinoma of prostate (CaP) (age of 72). B
      CLL treatment was chlorambucil for 2 years and follow-up subsequently. CRCC
      treatment was radical transperitoneal nephrectomy. Due to locally advanced CaP
      bilateral orchiectomy and radical external beam radiotherapy were performed.
      Patients is alive 30 months without any signs of any malignity. Incidence of
      multiple malignancies and particularly triplicities are discussed in this
      article. Authors point out pertinence of radical therapeutic approach also in
      multiple malignancies and oncological screening not only in patients with
      heamatological malignancy, but considering it in all tumours.

PMID- 14686259
TI  - [Laparoscopic anti-reflux surgery].
AB  - The indication for antireflux surgery despite consequent PPI medication includes:
      persisting disease with non-acid associated symptoms, such as volume reflux,
      recurrent hoarseness bronchiopulmonal reflux symptoms, in compliance with PPI,
      recurrent or persisting esophagitis. Our standard procedure is the short full
      Nissen wrap. Only in a 70% esophageal pump disturbance we actually apply a
      partial Toupet wrap. In 412 operations (Nissen 82%, Toupet 18%) during one year
      we observed 1.9% persisting postoperative dysphagia, 5% reflux relapses and 2%
      gas bloat syndrome of which 1 patient (0.2%) was re-operated. Significant
      differences between both procedures regarding the rate of function and
      complication have not been seen. Quality of life nearly came up to that of non
      operated healthy patients and was much better than before surgery. The high
      acceptance of laparoscopic antireflux surgery in a highly selected collective
      caused a revival of antireflux surgery by minimal invasive methods.

PMID- 14686260
TI  - [Does saphenous vein saving surgery have a role in the therapy of primary
      varices?].
AB  - Venous grafts retrieved from long saphenous veins are the best conduits for
      vascular and coronary reconstructions. The demand for such grafts rise
      continuously with the development of vascular and coronary surgery. Surgeons were
      soon confronted with the problem whether the saphenous trunk in patients with
      varicose veins may be used for grafting or not. Saphenous vein saving surgery
      means intentional renouncement of removing the saphenous trunk during varicose
      vein surgery and saving it for a possible graft in the future. Opinions whether
      such procedures are substantiated differ widely and concern both the suitability
      of such grafts and the fact that lowering the radicality of varicose vein surgery
      increases the probability of varicose vein recurrence. The saphenous trunk in
      primary varicose veins is not diffusely degenerated, it usually shows only a few
      local bulges and is basically compatible for the use as a vascular or coronary
      artery conduit; it does not dilate aneurysmatically when transplanted into the
      arterial circulation. Crossectomy disconnects saphenofemoral junction, the most
      frequent source of reflux, abolishes even the most serious venous derangement and
      restores normal venous hemodynamics; stripping brings about no further immediate
      amelioration. Recurrence of varicose veins is more frequent when crossectomy
      alone is performed in comparison with crossectomy and stripping, but nor
      crossectomy combined with stripping is able to reliably prevent recurrence,
      because the distinct tendency to recur is a characteristic feature of varicose
      disease. Saphenous vein saving surgery can be efficiently supplemented by
      sclerotherapy during follow-up. The excellent hemodynamic improvement achieved
      immediately after crossectomy can be preserved for many years during follow-up by
      repeated applications of sclerotherapeutic agents. In this way necessary
      conditions for a rapid and mostly a definitive healing of varicose ulcers can be
      established. In addition, preservation of a possible graft for arterial
      reconstructions is relevant in elderly patients.

PMID- 14686261
TI  - [A surgeon's view on the importance of positron emission tomography--PET (with
      emphasis on lung neoplasms)].
AB  - OBJECTIVE: PET became a successful method in preoperative evaluation of patients
      with cancer. We question whether PET scan can answer critical surgeons' requests
      such as distinguish benign and malign lesions, evaluation of cancer
      dissemination, evaluation of the pleural effusions, and also to detect early
      cancer recurrence. METHODS: Between September 1999 and December 2001, 39 patients
      underwent a PET scan and we evaluated its benefit in further treatment of
      patients. Standard PET techniques were used. RESULTS: In 20 patients (52%)
      results of PET scan were in correlation of clinical diagnosis and stage of cancer
      disease, partial difference between FDG-PET and clinical diagnosis was in 8
      patients (20%), next treatment was changed in 11 patients (28%). CONCLUSION: We
      conclude, that dedicated PET could be valuable tool in the diagnosis and staging
      of cancer disease, especially in verifying cancer dissemination, recurrence of
      the cancer. PET scan can be misleading in evaluation of the mediastinal
      lymphnodes and pleural effusions.

PMID- 14686262
TI  - IDN's auction, trade put supply chain in reverse.

PMID- 14686263
TI  - Price survey. OR glove prices to drop slightly.

PMID- 14686264
TI  - Disaster plans often neglect materials.

PMID- 14686265
TI  - Hospitals save with digital video networks.

PMID- 14686266
TI  - Recreational music-making: a cost-effective group interdisciplinary strategy for
      reducing burnout and improving mood states in long-term care workers.
AB  - OBJECTIVES: This controlled, prospective, randomized study examined the clinical
      and potential economic impact of a 6-session Recreational Music-making (RMM)
      protocol on burnout and mood dimensions, as well as on Total Mood Disturbance
      (TMD) in an interdisciplinary group of long-term care workers. METHODS: A total
      of 112 employees participated in a 6-session RMM protocol focusing on building
      support, communication, and interdisciplinary respect utilizing group drumming
      and keyboard accompaniment. Changes in burnout and mood dimensions were assessed
      with the Maslach Burnout Inventory and the Profile of Mood States respectively.
      Cost savings were projected by an independent consulting firm, which developed an
      economic impact model. RESULTS: Statistically-significant reductions of multiple
      burnout and mood dimensions, as well as TMD scores, were noted. Economic-impact
      analysis projected cost savings of $89,100 for a single typical 100-bed facility,
      with total annual potential savings to the long-term care industry of $1.46
      billion. CONCLUSIONS: A cost-effective, 6-session RMM protocol reduces burnout
      and mood dimensions, as well as TMD, in long-term care workers.

PMID- 14686267
TI  - The impact of recreational music-making for long-term care workers.

PMID- 14686268
TI  - On the psycho- in psychophysiology: notes for a history of the mind-body effect.
AB  - One hundred and twenty-five years of the dialogue between psychology and
      physiology reveal a vibrant discussion about the mind-body effect--the ability of
      waking consciousness to influence its own normally unconscious physiology through
      conscious intention, and conversely, the reciprocal effect of physiology on
      consciousness. In the early phase, the data remained largely anecdotal.
      Scientific study of the emotions then opened the door to dynamic theories of the
      subconscious. Such formulations, however, were repeatedly overshadowed by
      concurrent advances in brain neurophysiology, which rejected not only any
      exploration of the unconscious that relied on the method of symbolism, but also
      the reality of the unconscious itself. Nevertheless, scientific advances at the
      interface between psychology and physiology persisted. Since the 1950s, however,
      there has been an explosion of new work in the neurosciences at the interface
      between molecular genetics, endocrinology, neurology, immunology, and psychiatry.
      This has fueled both new research and renewed discussion about the mind-body
      effect, a dialogue that is now, in part, also a response to a counter-culture
      revolution occurring at the interface between the delivery of clinical services
      throughout the healthcare professions and an increasingly sophisticated consumer
      demand for alternative and complementary therapies.

PMID- 14686270
TI  - Homeodynamics in consciousness.

PMID- 14686269
TI  - Impact of a residential psychosocial program for cancer patients: a focus group
      investigation.
AB  - Focus groups of past program participants were conducted to explore the impact of
      a novel residential psychosocial intervention for cancer patients. All
      participants had attended the program between 6 months and 1 year prior to the
      study. The intention was to elicit a broad range of feedback regarding the
      program's effects on people living with cancer. Of particular interest was the
      assessment of lasting outcomes for participants, and possibilities for program
      improvement. This article reports the substantive understanding resulting from
      these focus groups, and discusses the beneficial impact, effective program
      characteristics, and controversial issues of residential psychosocial
      programming.

PMID- 14686271
TI  - [Assessment of commercial feeds for parrots].
AB  - Twenty-five commercial parrot feeds were analyzed and compared with a guideline
      as to the nutrient requirements of parrots. There was a large variation in the
      composition of the different feeds. The protein content differed from 10.4 to
      20.6%. A total of 18 feeds had a low protein content and thus is only suitable
      for adult animals during maintenance. The calcium content varied from 0.08 to
      2.21 g/100 g. Seven out of the 13 seed mixtures had a calcium content lower than
      the requirement. Calcium deficiency can lead to rachitis, osteomalacia, secondary
      nutritional hyperparathyroidism and hypocalcaemia syndrome in African Grey
      parrots. With the help of the analyzed composition, the different feeds were
      judged on their quality. Apart from macronutrients, minerals and trace elements,
      the fatty acid composition of the feeds was also determined. Atherosclerosis is a
      common disease in parrots, and an important risk factor is elevated plasma
      cholesterol. Plasma cholesterol is strongly influenced by fat content and fatty
      acid composition of the diet. Based on the fatty acid composition, the effect of
      a diet on plasma cholesterol can be predicted. All feeds had a similar, small
      effect on plasma cholesterol. However, the feeds differed strongly in their alpha
      linolenic acid content (0.03-0.65 g/MJ). According to literature data alpha
      linolenic acid could have an anti-atherosclerotic effects.

PMID- 14686272
TI  - [The preventive program prevented?].

PMID- 14686273
TI  - [The ins and outs of the digital Repertory].

PMID- 14686274
TI  - [Hormonal growth promoters].

PMID- 14686275
TI  - [Blackhead in turkeys: predictable disaster makes a problem to be discussed].

PMID- 14686276
TI  - [Mosquitoes disappear].

PMID- 14686277
TI  - [It is very stimulating to be able to work in "the big brain'].

PMID- 14686278
TI  - [State secretary Rutte visiting the KNMvD. Open discussion about the new pension
      law].

PMID- 14686279
TI  - [Katja Buchsbaum: "harmonization gives more value to the European Union"].

PMID- 14686280
TI  - New AIDS trust created to galvanize world leaders.

PMID- 14686281
TI  - Global AIDS conference ends on hopeful note amid startling reports.

PMID- 14686282
TI  - Hope for AIDS vaccine fades with news of superinfection.

PMID- 14686283
TI  - Records release. HIV test admissible without chain of custody showing.

PMID- 14686284
TI  - Barcelona conference details AIDS pandemic around the world.

PMID- 14686285
TI  - Children. Crisis approaching from orphans created by HIV/AIDS.

PMID- 14686286
TI  - Negligence. $2.5-million award set aside for untimely reporting of HIV status.

PMID- 14686287
TI  - Extradition stayed for Georgia escapee dying of AIDS in California.

PMID- 14686289
TI  - Texas educates inmates to halt spread of HIV.

PMID- 14686288
TI  - Prison. Correctional staff not liable for inmate's death from AIDS.

PMID- 14686290
TI  - New fusion inhibitor drug stops HIV from spreading.

PMID- 14686291
TI  - Antiretroviral therapy update from the 2nd IAS Conference.

PMID- 14686292
TI  - Pharmacology in Paris.

PMID- 14686293
TI  - Panel on clinical practices issues revised adult ART guidelines.

PMID- 14686294
TI  - Basic lipids: NCEP made easy for HIV patients.

PMID- 14686295
TI  - Focusing on "prevention in positives".

PMID- 14686296
TI  - The Internet's role as modern bathhouse is being scrubbed. On-line hookups
      increasingly popular among MSM.
AB  - The Internet increasingly is taking over as a major source for men who have sex
      with men to meet for quick, anonymous, and often unsafe sexual encounters.
      Fortunately, some organizations have begun Internet programs to target these at
      risk groups and provide HIV-prevention interventions both on-line and in time.

PMID- 14686297
TI  - Interventions can ease dangers of cybersex. Counselors educate while in
      chatrooms.
AB  - Successful Internet prevention programs need to reach the population that is most
      at risk for HIV and that uses the Internet as a major avenue for meeting
      anonymous sexual partners. Several regional programs have found ways to do this,
      without a lot of cost involved.

PMID- 14686298
TI  - Rapid HIV test yields counseling, referrals. Clients report satisfaction with
      rapid test.
AB  - Recent studies of the rapid HIV test's use among at-risk populations show that
      the test can be a valuable tool when combined with counseling in intervention
      programs because the percentage of people who stay to receive their test results
      is very high.

PMID- 14686299
TI  - Study: condoms in school do not promote sex. Very few high schools offer condoms,
      however.
AB  - A recent study of high school student behavior in schools where condoms are
      available suggests that the mere fact of having condoms there does not increase
      sexual behavior among students. Researchers found that in schools where condoms
      are available, condom use was significantly higher among sexually active
      students.

PMID- 14686300
TI  - Rapid tests could mean trouble for ADAPS. Increased HIV testing could flood
      system.
AB  - As if AIDS Drug Assistance Program directors weren't worried enough, they have a
      new potential problem to discuss: how would the states and ADAP programs handle a
      large influx of new HIV and AIDS patients if the Centers for Disease Control and
      Prevention succeeded in significantly increasing HIV testing rates?

PMID- 14686301
TI  - FDA notifications. NRTI Emtriva receives FDA approval.
AB  - The Food and Drug Administration has approved Emtriva (FTC, emtricitabine), a new
      nucleoside reverse transcriptase inhibitor to be used in combination with other
      antiretroviral agents for the treatment of patients with HIV infection.

PMID- 14686302
TI  - Hepatitis C and HIV co-infection: an update.

PMID- 14686303
TI  - HIV/AIDS stigma.

PMID- 14686304
TI  - New test being launched to pin new HIV cases. New STARHS test will clarify
      problem areas.
AB  - At the 2003 HIV Prevention Conference, researchers presented a sobering picture
      of the remaining challenges in the battle to reduce HIV transmission as well as
      the struggle to increase HIV testing and treatment. While a new HIV diagnostic
      test brings hope, several problem areas still need to be addressed.

PMID- 14686305
TI  - Needle exchanges do not boost drug use, study says. IDU remains major HIV risk
      factor.
AB  - While the latest data show injection drug use remains a major factor in AIDS
      causes in the United States, a new study offers evidence that needle exchange
      programs do not cause an increase in injection drug use. CDC data show that HIV
      diagnoses reported among intravenous drug users has declined 42%, and most public
      health officials attribute that to needle exchange programs and other
      initiatives.

PMID- 14686306
TI  - Testing gains shown in antiretroviral resistance. Research addresses new
      recommendations.
AB  - Resistance testing has proved useful in treating some HIV patients, but it's
      expense and its inconsistent value in predicting the future course of HIV disease
      have left clinicians with some doubts about how best to use it.

PMID- 14686307
TI  - Jailed youth at high risk of HIV, researchers find. Youngest kids also have high
      risk behaviors.
AB  - Investigators have found that among incarcerated youths in Chicago, there are
      very high rates of behavior, which place that group fo children and teen-agers at
      risk for HIV infection. The study examined youth, ages 10 to 18, who were held
      between 1995 and 1998 at the Cook County Juvenile Temporary Detention Center,
      using the AIDS Risk Behavior Assessment.

PMID- 14686308
TI  - Treatment for cocaine use may have HIV benefits. Study shows how to achieve best
      results.
AB  - While it is common knowledge that methadone treatment or any treatment that helps
      people quit injection drug activity can have a positive effect on preventing HIV
      infection, the impact of cocaine addiction treatment is less commonly understood.
      A recent study found an average 40% reduction in HIV risk behavior among cocaine
      dependent patients when they are provided with intense outpatient psychosocial
      treatment.

PMID- 14686309
TI  - FDA notifications. Reyataz is approved for HIV treatment.
AB  - Reyataz, protease inhibitor, is to be used in combination with other
      antiretroviral agents for the treatment of patients with HIV infection. The most
      common laboratory abnormality observed is hyperbilirubinemia.

PMID- 14686310
TI  - Effective triage strategies for HIV/AIDS.

PMID- 14686311
TI  - The spectrum of access.

PMID- 14686312
TI  - ARV in Sub-Saharan Africa: 17 reports.

PMID- 14686313
TI  - Medecins Sans Frontieres (MSF) antiretroviral treatment projects worldwide.

PMID- 14686314
TI  - Notes on hepatitis C infection from the IAS Paris conference.

PMID- 14686315
TI  - Preventing HIV/AIDS in India: points to ponder.

PMID- 14686316
TI  - Stumbling forward: new drugs bring new questions.

PMID- 14686317
TI  - Progress at last? South Africa relents on HIV drugs.

PMID- 14686318
TI  - [Advances in the study on chemical constituents and pharmacology of Acanthopanax
      senticosus (Rupr. et Maxim.)].

PMID- 14686319
TI  - Putting the International Space Station to work.
AB  - The International Space Station (ISS) is the largest international cooperative
      science and technology project ever undertaken. Involving the United States,
      Russia, Japan, Canada and 10 ESA Member States, it is now rapidly becoming a
      reality in orbit, offering unprecedented access for research and applications
      under space conditions. Europe has invested heavily in this endeavour and plans
      to exploit that investment by a vigorous utilisation of the ISS for life and
      physical sciences research and applications, space science, Earth observation,
      space technology development, the promotion of commercial access to space, and
      the use of space for educational purposes. In recent years, ESA has engaged in an
      intensive promotional effort to encourage potential user communities to exploit
      the novel opportunities that the ISS offers. It has also made significant
      financial commitments to develop both multi-user facilities for life and physical
      sciences studies in the Columbus Laboratory, and observational and technology
      exposure instruments using the external Columbus mounting locations, as well as
      giving financial support to promote commercial and educational activities. ESA
      has now elaborated a European Strategy for the efficient utilisation of the ISS
      by European scientists and other users, which is being coordinated with the
      Agency's Member States contributing to the ISS Programme, and with the European
      Science Foundation (ESF). In cooperation with the European Commission, ESA is
      also fostering synergy with the European Commission's Framework Programmes in
      terms of shared R&D objectives. This article describes the plan that has been
      evolved to integrate all of these various elements.

PMID- 14686320
TI  - Mars Surveyor Program '01 Mars Environmental Compatibility Assessment wet
      chemistry lab: a sensor array for chemical analysis of the Martian soil.
AB  - The Mars Environmental Compatibility Assessment (MECA) instrument was designed,
      built, and flight qualified for the now canceled MSP (Mars Surveyor Program) '01
      Lander. The MECA package consisted of a microscope, electrometer, material patch
      plates, and a wet chemistry laboratory (WCL). The primary goal of MECA was to
      analyze the Martian soil (regolith) for possible hazards to future astronauts and
      to provide a better understanding of Martian regolith geochemistry. The purpose
      of the WCL was to analyze for a range of soluble ionic chemical species and
      electrochemical parameters. The heart of the WCL was a sensor array of
      electrochemically based ion-selective electrodes (ISE). After 20 months storage
      at -23 degrees C and subsequent extended freeze/thawing cycles, WCL sensors were
      evaluated to determine both their physical durability and analytical responses. A
      fractional factorial calibration of the sensors was used to obtain slope,
      intercept, and all necessary selectivity coefficients simultaneously for selected
      ISEs. This calibration was used to model five cation and three anion sensors.
      These data were subsequently used to determine concentrations of several ions in
      two soil leachate simulants (based on terrestrial seawater and hypothesized Mars
      brine) and four actual soil samples. The WCL results were compared to simulant
      and soil samples using ion chromatography and inductively coupled plasma optical
      emission spectroscopy. The results showed that flight qualification and prolonged
      low-temperature storage conditions had minimal effects on the sensors. In
      addition, the analytical optimization method provided quantitative and
      qualitative data that could be used to accurately identify the chemical
      composition of the simulants and soils. The WCL has the ability to provide data
      that can be used to "read" the chemical, geological, and climatic history of
      Mars, as well as the potential habitability of its regolith.

PMID- 14686321
TI  - Ronald Dworkin on abortion and assisted suicide.
AB  - In the first part of this article, I raise questions about Dworkin's theory of
      the intrinsic value of life and about the adequacy of his proposal to understand
      abortion in terms of different ways of valuing life. In the second part of the
      article, I consider his argument in "The Philosophers' Brief on Assisted
      Suicide", which claims that the distinction between killing and letting die is
      morally irrelevant, the distinction between intending and foreseeing death can be
      morally relevant but is not always so. I argue that the killing/letting die
      distinction can be relevant in the context of assisted suicide, but also show
      when it is not. Then I consider why the intention/foresight distinction can be
      morally irrelevant and conclude by presenting an alternative argument for
      physician-assisted suicide.

PMID- 14686322
TI  - Full-length genome characterization of HIV type 1 subtype C isolates from two
      slow-progressing perinatally infected siblings in South Africa.
AB  - Isolation and characterization of HIV-1 from asymptomatic, slow-progressing
      individuals are important in studying viral pathogenesis and facilitate the
      development of vaccines and antivirals. In this study we identified two slow
      progressing HIV-1-infected siblings, isolated viruses, and sequenced the full
      length genome, to identify virus attenuations that may contribute to their
      altered rate of disease progression. Proviral DNA from strains 99ZATM10 and
      01ZATM45 was isolated from peripheral blood mononuclear cells (PBMC)
      coculture.Virtually full-length genomes and long terminal repeat (LTR) regions
      were polymerase chain reaction (PCR) amplified, sequenced, and assembled to
      generate the complete genomes. Phylogenetic analysis confirmed that both isolates
      were subtype C throughout their genome. Predicted amino acid sequence analysis
      for all the HIV-1 proteins showed that both viruses had open reading frames for
      all genes, and encoded proteins of the expected length, except for the rev gene.
      The 3' end of rev exon 2 did not have the 16-amino acid (aa) truncation
      characteristic of subtype C viruses, and in addition, had a three-aa extension
      (GlyCysCys). Rev is a necessary regulatory factor for HIV expression, and changes
      in the protein may affect viral replication. These results suggest that slower
      HIV disease progression in these children may be attributed, at least in part, to
      an altered Rev protein.

PMID- 14686323
TI  - Replies to Endicott, Kamm and Altman.

PMID- 14686324
TI  - Genotypic resistance of antiretroviral drugs among drug-naive HIV type 1 patients
      with the background of long-term access-easy zidovudine therapy.
AB  - The prevalence of transmitted resistance to antiretroviral drugs varies
      geographically, with little known about this effect in Asia. In Korea, zidovudine
      has been widely administered, without charge, through the National AIDS program
      since the early 1990s; with other potent antiretroviral agents also being
      introduced in the late 1990s. An analysis of the drug susceptibility to
      antiretroviral drugs was performed by genotyping of the drug-resistant mutations
      in HIV on plasma samples from 50 HIV-infected patients who had received no
      treatment, between February 1998 and November 2002, which was interpreted
      according to the consensus guidelines of the International AIDS Society-USA
      panel. The median CD4 cell count was 100 cells/mm3; the mean plasma RNA level was
      (5.19 +/- 0.56) log copies per milliliter. Of the 50 subjects tested 4 (8.0%) had
      one or more major drug-resistance mutation. The prevalence of resistance to
      multiple classes of drugs was 2.0%. No mutations, associated with resistance to
      non nucleoside reverse transcriptase inhibitors, were identified. Resistant
      mutations of the reverse-transcriptase gene were found at codons 67, 70, 118,
      215, and 219, and a resistant mutation of the protease gene was found only at
      codon 46 (2.6%, 1 of 39). There was an 8.0% prevalence of primary drug resistance
      to antiretroviral drugs in Korean patients infected with HIV-1.

PMID- 14686325
TI  - Identification of HIV type 2 subtype B transmission in East Asia.
AB  - We isolated an HIV-2 strain (01JP-IMCJ/KR020) from a Korean patient who has lived
      in Japan for the past 6 years. He was infected with HIV-2 through heterosexual
      contacts in either Korea or Japan. The phylogenetic analyses based on the near
      full-length nucleotide sequence revealed that 01JP-IMCJ/KR020 belongs to HIV-2
      subtype B cluster with high bootstrap support. This isolate harbors a 13
      nucleotide insertion upstream of the NF-KB site, which is one of the sequence
      signatures specific to HIV-2 subtype B. This represents the first report of HIV-2
      subtype B transmission in East Asia; three cases of HIV-2 subtype A infection
      have been reported in Korea in 1991-1998. This suggests that at least sporadic
      transmission of HIV-2, including both subtypes A and B, occurs in East Asia. It
      is necessary to keep monitoring HIV-2 to see whether there is an increasing trend
      toward HIV-2 infection in this particular area in Asia.

PMID- 14686326
TI  - Characterization of HIV type 1 heterosexual transmission in Yunnan, China.
AB  - The earliest HIV-1 epidemic in China started in Yunnan province, which continues
      to be one of the most severe areas affected. While HIV-1 infections are spreading
      rapidly among injection drug users (IDUs) in China, sexual transmission of HIV-1
      has also been confirmed, threatening the general population. Recent survey data
      indicated that heterosexual transmission of HIV-1 in Yunnan was steadily
      increasing. Diverse HIV-1 strains, including subtype B, C, CRF01, and CRF08, are
      circulating among individuals who acquired HIV through sexual contacts. Multiple
      HIV-1 subtypes, including subtypes B, C, and CRF08, were also detected among
      IDUs. In comparison with other IDU cohorts, intersubject env sequence variation
      was much higher amongIDUs in Yunnan. Growing evidence suggests that unprotected
      sex continues to occur at high rates among IDUs and their sex partners.
      Intervention strategies are urgently needed to target individuals at high risk
      for HIV heterosexual transmission and injection drug use. The complex pattern of
      HIV-1 distribution in the high-risk populations in Yunnan may have important
      implications for HIV transmission as well as vaccine development and evaluation.

PMID- 14686327
TI  - Differential prevalence of HIV type 1 subtype B and CRF01_AE among different
      sexual transmission groups in Tokyo, Japan, as revealed by subtype-specific PCR.
AB  - We determined the subtype of HIV-1 in 89 infected individuals attending three
      reference hospitals located in the Tokyo metropolitan area of Japan. Subtyping
      was performed with subtype-specific polymerase chain re-action (PCR)
      distinguishing subtype A, B, C, and CRF01_AE and/or phylogenetic analysis of HIV
      1 env C2V3C3 sequences. Subtype-specific PCR provided unequivocal results in 97%
      of samples. Sixty-five subjects were infected with subtype B, 16 with CRFO1_AE, 4
      with subtype A, 1 with CRF02_AG, and 3 with subtype C. Among 31 Japanese
      individuals infected through heterosexual contact, 13 were infected with subtype
      Band 12 with CRFO1_AE. All of the 41 Japanese men infected through homosexual
      contact harbored subtype B. These results indicate that subtype B is exclusively
      predominant in a homosexually transmitted group, whereas subtype B and CRFO1_AE
      are evenly predominant in a heterosexually transmitted group.

PMID- 14686328
TI  - Selling yourself: Titmuss's argument against a market in blood.
AB  - This article defends Richard Titmuss's argument, and Peter Singer's sympathetic
      support for it, against orthodox philosophical criticism. The article specifies
      the sense in which a market in blood is "dehumanising" as having to do with a
      loss of "imagined community" or social "integration," and not with a loss of
      valued or "deeper" liberty. It separates two "domino arguments"--the
      "contamination of meaning" argument and the "erosion of motivation" argument-
      which support, in different but interrelated ways, the claim that a market in
      blood is "imperialistic." Concentrating on the first domino argument the article
      considers the view that monetary and non-monetary meanings of the same good can
      co-exist given the robustness of certain kinds of relationship and joint
      undertakings within which gifts can figure. It argues that societal relationships
      are vulnerable or permeable to the effects of the market in a way that those
      constitutive of the personal sphere are not. General, more broadly political
      questions remain unanswered but the core of Titmuss's original and challenging
      argument remains and can be presented in a defensible form.

PMID- 14686329
TI  - [Modern conceptions about regulation of cell cycle in plants].
AB  - The most modern conceptions about regulation of cell cycle in plants are
      considered in the article. According to literary data, the main regulators of
      cell cycle are cyclines and cycline-dependent kinases. Four basic types of plant
      cyclines and series of cycline-depending kinases, that control different phases
      of cell cycle, are describe. As for the influence of physical factors
      (temperature, radiation, light, vibration, magnetic field and microgravity) on
      the parameters of cell cycle, then in most cases they arise similar reactions-
      increasing of the duration of cell cycle, that may be explained by the extension
      of presinthetic phase of the cycle. The study of influence of altered gravity on
      a cell proliferation is very important for understanding and further,
      investigations of the nature of peculiarities of a plant development and the
      study of molecular mechanisms of the cell cycle regulation under altered gravity.

PMID- 14686330
TI  - Frankensteins and cyborgs: visions of the global future in an age of technology.
AB  - This paper draws attention to the role of representation in the depiction of
      scientific and technological innovation as a means of understanding the
      narratives that circulate concerning the shape of things to come. It considers
      how metaphors play an important part in the conduct of scientific explanation,
      and how they do more than describe the world in helping also to shape
      expectations, normalise particular choices, establish priorities and create
      needs. In surveying the range of metaphorical responses to the digital and
      biotechnological age, we will see how technologies are regarded both as
      'endangerment' and 'promise.' What we believe 'technology' is doing to 'us'
      reflects important implicit philosophies of technology and its relationship to
      human agency and political choice; yet we also need to be alert to the
      assumptions about 'human nature' itself which inform such reactions. The paper
      argues that embedded in the various representations implicit in the new
      technologies are crucial issues of identity, community and justice: what it means
      to be (post)human, who is (and who is not) entitled to the rewards of
      technological advancement, what priorities (and whose interests) will inform the
      shape of global humanity into the next century.

PMID- 14686332
TI  - European guidelines on cardiovascular disease and prevention in clinical
      practice.

PMID- 14686333
TI  - Digestive disease week 2002, 19-22 May 2002, San Francisco, CA, USA.

PMID- 14686334
TI  - Acid Fast Club: special session in honour of Dr. M. Joseph (Jo) Colston.

PMID- 14686335
TI  - Recent therapeutic advances in inflammatory bowel disease.

PMID- 14686336
TI  - COX-2 inhibitors, NO-NSAIDs and beyond.

PMID- 14686337
TI  - Analysis. Choice bites in Boca Raton.

PMID- 14686338
TI  - Medicinal Chemistry - 28th National Symposium. 8-12 June 2002, San Diego, CA,
      USA.

PMID- 14686339
TI  - Responses of cultured human airway epithelial cells treated with diesel exhaust
      extracts will vary with the engine load.
AB  - Epidemiologic evidence suggests that increased morbidity and mortality are
      associated with the concentrations of ambient air particulate matter (PM). Many
      sources contribute to the particulate fraction of ambient air pollution,
      including diesel exhaust particulates (DEP). Diesel exhaust also contributes gas
      phase pollutants to the atmosphere, and gaseous copollutants may influence the
      toxicity of PM. The composition of diesel exhaust varies greatly depending on the
      engine load conditions as well as other factors. To determine whether different
      diesel exhaust composition can affect lung cell resposes, the effects of of
      diesel exhaust extracts derived from different engine loads were examined on
      normal human bronchial epithelial cells (NHBE) in vitro. Diesel exhaust was
      collected into chilled impingers containing phosphate-buffered saline (PBS).
      Cultured NHBE cells were treated with 0 to 500 microg/well extract from
      approximately 0% engine load (termed low load or LL) or extract from
      approximately 75% engine load (termed high load or HL) for 24 h. The HL extract
      was cytotoxic at 500 microg compared to controls as measured by (51)Cr release.
      Production of the neutrophil chemotaxin interleukin 8 (IL-8) was decreased 4.7
      fold in cells treated with 500 microg LL extract, whereas cells treated with 500
      microg HL extract showed a 2.4-fold increase in IL-8 release. Production of the
      inflammatory and immune system mediator prostaglandin E(2) (PGE(2)) was increased
      up to 2.5-fold in cells treated with HL extract, but unchanged with other
      treatments. Melittin stimulation of cells showed that the LL extract had an
      inhibitory effect on PGE(2) release at 500 microg. Differences in carbonyl
      content of the extracts were found by high performance liquid chromatography/mass
      spectroscopy HPLC/MS, with the HL extract having more intermediate size carbonyls
      (i.e. with six to nine carbons). The data suggest that the response of NHBE cells
      to treatment with diesel exhaust will vary depending on the constituent
      components of the exhaust.

PMID- 14686340
TI  - Anti-infectives: the next generation.

PMID- 14686341
TI  - Novel cancer therapies.

PMID- 14686342
TI  - Treatment of addiction.

PMID- 14686343
TI  - Fluoroquinolones.

PMID- 14686345
TI  - American Urological Association - 97th Annual Meeting.

PMID- 14686344
TI  - Structure-based drug design.

PMID- 14686346
TI  - Progress in sexual dysfunction.

PMID- 14686347
TI  - American Society of Gene Therapy - Fifth Annual Meeting.

PMID- 14686348
TI  - American Diabetes Association - 62th Scientific Sessions.

PMID- 14686349
TI  - Alternative routes of insulin administration.

PMID- 14686350
TI  - Decisional authority and moral responsibility of patients and clinicians in the
      context of preimplantation genetic diagnosis.
AB  - Case reports reveal that clinicians applying preimplantation genetic diagnosis
      are increasingly confronted with requests by patients which they consider
      ethically problematic. These requests raise the question to what extent
      physicians share responsibility for the welfare of the future child. Two
      categories of situations are analysed: when patients unilaterally review the
      agreement made with the medical staff and when they request an application that
      increases rather than reduces the risk of having a termination of pregnancy. It
      is concluded that physicians have their own responsibility in the process, which
      allows them to introduce conditions before starting infertility treatment.

PMID- 14686351
TI  - Infertility therapy-associated multiple pregnancies (births): an ongoing
      epidemic.

PMID- 14686353
TI  - World Congress of Pharmacology - XIVth Annual Meeting.

PMID- 14686352
TI  - Analysis. Special effects.

PMID- 14686354
TI  - HSJ campaign. Dereliction of duty.

PMID- 14686355
TI  - Neuropharmacology and behavioral pharmacology.

PMID- 14686356
TI  - Analysis. 2020 vision.

PMID- 14686358
TI  - Throwing light on thrombosis.

PMID- 14686357
TI  - China faces up to HIV/AIDS epidemic. World AIDS day is marked by launch of huge
      public-awareness campaign.

PMID- 14686360
TI  - New drugs I.

PMID- 14686359
TI  - UNICEF gloomy on child development goals.

PMID- 14686361
TI  - New drugs II.

PMID- 14686362
TI  - Medicines adviser resigns over HRT warning.

PMID- 14686363
TI  - Mucosal immunology - 11th International Congress.

PMID- 14686364
TI  - American Red Cross to screen blood for Chagas' disease.

PMID- 14686365
TI  - Homing instinct.

PMID- 14686367
TI  - Anti-cancer drug discovery and development summit.

PMID- 14686366
TI  - India unprepared for antiretroviral treatment plan.

PMID- 14686368
TI  - Medicare reforms receive mixed reaction. Bill is passed by Congress, but
      wrangling continues.

PMID- 14686370
TI  - Neurovirology Fourth International Symposium and Neuroscience of HIV Infection
      Tenth Conference.

PMID- 14686369
TI  - What works. On measuring results.

PMID- 14686371
TI  - Collegium Internationale Neuro-Psychopharmacologicum - 23rd Congress.

PMID- 14686372
TI  - Migration, human rights, and health.

PMID- 14686373
TI  - Localization and function of 5-HT2 receptors.

PMID- 14686374
TI  - Targeting ubiquitinylation for drug discovery.

PMID- 14686375
TI  - Neurodegeneration - Fifth International Meeting. In Alzheimer's disease,
      Parkinson's disease and related disorders.

PMID- 14686377
TI  - Dermatology - 20th World Congress.

PMID- 14686376
TI  - Pesticides at work and at home: exposure of migrant farmworkers.

PMID- 14686378
TI  - New drugs for respiratory diseases - Fifth International Conference.

PMID- 14686380
TI  - Lower urinary tract disorders - Ray Fuller Symposium. Physiology, pharmacology
      and therapeutics approaches.

PMID- 14686379
TI  - Lower urinary tract disorders - Ray Fuller Symposium.

PMID- 14686381
TI  - Small but perfectly formed.

PMID- 14686382
TI  - AIDS - XIVth International Conference. New drugs, new targets symposium.

PMID- 14686383
TI  - Anti-infectives: the way forward.

PMID- 14686385
TI  - American Chemical Society - 224th National Meeting.

PMID- 14686384
TI  - Analysis. Are you talking to me?

PMID- 14686386
TI  - Novel antimicrobial agents and HIV therapy.

PMID- 14686387
TI  - Cancer tackled from all angles.

PMID- 14686388
TI  - New drug highlights I.

PMID- 14686389
TI  - New drug highlights II.

PMID- 14686390
TI  - International Narcotics Research Conference - 33rd Meeting.

PMID- 14686391
TI  - Tangled wrangles.

PMID- 14686392
TI  - Venoms to Drugs 2002 Conference.

PMID- 14686394
TI  - Drugs from natural products - Third Annual Meeting.

PMID- 14686393
TI  - There's no telling.

PMID- 14686395
TI  - Model organisms for drug discovery - IBC Conference.

PMID- 14686396
TI  - Bioorganic Chemistry 2002 - Sixth International Symposium.

PMID- 14686397
TI  - Analysis. No little concern.

PMID- 14686398
TI  - Drug discovery technology 2002. Start-up showcase and structure-based drug
      design.

PMID- 14686399
TI  - Target validation and lead optimization.

PMID- 14686400
TI  - Convergence of IT and R&D, and screening.

PMID- 14686401
TI  - Keynote lectures.

PMID- 14686402
TI  - Beyond pills and jabs. Researchers develop new ways to get drugs to the right
      place at the right time.

PMID- 14686403
TI  - Drug discovery case histories.

PMID- 14686404
TI  - Controlled Release Society - 29th Annual Meeting and Exposition.

PMID- 14686405
TI  - Pulmonary drug delivery.

PMID- 14686406
TI  - Regarding "Postoperative infection associated with polyester patch angioplasty
      after carotid endarterectomy".

PMID- 14686407
TI  - Gene testing is easy, it's the next bit that's hard.

PMID- 14686409
TI  - A warning that must not be ignored.

PMID- 14686408
TI  - Test blunders risk needless abortions.

PMID- 14686410
TI  - The final countdown.

PMID- 14686411
TI  - Trials and errors: with drug companies now testing new medicines in all parts of
      the globe, are ethical standards being compromised?

PMID- 14686412
TI  - Doctors don't fall for the hard sell.

PMID- 14686413
TI  - Bad drives out the good: bizarre embryo experiments are casting a pall over
      worthwhile research.

PMID- 14686414
TI  - Brave new treatments: womb treatments and "artificial eggs" are on the horizon.
      But just how safe are existing fertility treatments?

PMID- 14686415
TI  - Studies provoke shock and horror.

PMID- 14686416
TI  - Risky business.

PMID- 14686417
TI  - Why not just say yes? American ethics boards are nervous about approving street
      drugs for use in research. Their concerns are more about politics than safety.

PMID- 14686418
TI  - No smokescreen.

PMID- 14686419
TI  - Cool reception for drug to limit smoking damage.

PMID- 14686420
TI  - Playing God? Interview by Laura Spinney.

PMID- 14686421
TI  - Ministry leadership. The sponsored leader.

PMID- 14686422
TI  - Metastatic malignant solitary fibrous tumour to the infra-temporal fossa.
AB  - Malignant solitary fibrous tumours (MSFTs) are rare tumours of fibrous origin,
      which can occur at all anatomical sites and represent 20% of solitary fibrous
      tumours. Fine-needle aspiration cytology is not able to distinguish benign from
      malignant disease, and sufficient tissue has to be obtained for accurate
      histological diagnosis to be made. Lesions > 10 cm in diameter and incomplete
      resection or non-resectability are predictive factors for poor long-term
      survival. We present a 57-year-old patient with a presumably metastatic MSFT from
      the peritoneal cavity to the skull-base who is in a stable state 17 months after
      surgical debulking of the skull-base and removal of the peritoneal lesion,
      followed by post-operative chemotherapy. We suggest the terminology metastatic
      malignant solitary fibrous tumour for a description of this disease.

PMID- 14686423
TI  - Arkansas system develops its own intranet.

PMID- 14686424
TI  - Mission is like a quilt.

PMID- 14686425
TI  - Why is this happening to me/us?

PMID- 14686426
TI  - Hey, you--look at me.

PMID- 14686427
TI  - Traditional herbal medicine research with special reference to tetrandrine and
      related bis-benzylisoquinoline alkaloids: a preface to this special issue on
      herbal drugs.

PMID- 14686428
TI  - [Advances in the study on pharmacological actions of Polygonum cuspidatum Sieb.
      et Zucc.: clearing heat and detoxication].

PMID- 14686429
TI  - Space life sciences: gravity-related processes in plants.

PMID- 14686430
TI  - Gravitaxis and graviperception in flagellates.
AB  - There is strong evidence that gravitactic orientation in flagellates and ciliates
      is mediated by an active physiological gravireceptor rather than by passive
      alignment of the cells in the water column. In flagellates the threshold for
      graviorientation was found to be at 0.12 x g on a slow rotating centrifuge during
      the IML-2 mission on the Shuttle Columbia and a subsequent parabolic rocket
      flight (TEXUS). During the IML-2 mission no adaptation to microgravity was
      observed over the duration of the space flight, while gravitaxis was lost in a
      terrestrial closed environmental system over the period of almost two years.
      Sedimenting statoliths are not likely to be involved in graviperception because
      of the small size of the cells and their rotation around the longitudinal axis
      during forward locomotion. Instead the whole cytoplasmic content of the cell,
      being heavier than the surrounding aqueous medium (1.05 g/ml), exerts a pressure
      on the lower membrane. This force activates stretch-sensitive calcium specific
      ion channels which can be inhibited by the addition of gadolinium which therefore
      abolishes gravitaxis. The channels seem to mainly allow calcium ions to pass
      since gravitaxis is blocked by the addition of the calcium ionophore A23187 and
      by vanadate which blocks the Ca-ATPase in the cytoplasmic membrane. Recently, a
      gene for a mechanosensitive channel, originally sequenced for Saccharomyces, was
      identified in Euglena by PCR. The increase in intracellular free calcium during
      reorientation can be visualized by the fluorophore Calcium Crimson using laser
      excitation and image intensification. This result was confirmed during recent
      parabolic flights. The gated calcium changes the membrane potential across the
      membrane which may be the trigger for the reorientation of the flagellum. cAMP
      plays a role as a secondary messenger. Photosynthetic flagellates are suitable
      candidates for life support systems since they absorb CO2 and produce oxygen.
      Preliminary experiments are discussed.

PMID- 14686431
TI  - Hypergravity-induced changes in gene expression in Arabidopsis hypocotyls.
AB  - Under hypergravity conditions, the cell wall of stem organs becomes mechanically
      rigid and elongation growth is suppressed, which can be recognized as the
      mechanism for plants to resist gravitational force. The changes in gene
      expression by hypergravity treatment were analyzed in Arabidopsis hypocotyls by
      the differential display method, for identifying genes involved in hypergravity
      induced growth suppression. Sixty-two cDNA clones were expressed differentially
      between the control and 300 g conditions: the expression levels of 39 clones
      increased, whereas those of 23 clones decreased under hypergravity conditions.
      Sequence analysis and database searching revealed that 12 clones, 9 up-regulated
      and 3 down-regulated, have homology to known proteins. The expression of these
      genes was further analyzed using RT-PCR. Finally, six genes were confirmed to be
      up-regulated by hypergravity. One of such genes encoded 3-hydroxy-3
      methylglutaryl-Coenzyme A reductase (HMGR), which catalyzes a reaction producing
      mevalonic acid, a key precursor of terpenoids such as membrane sterols and
      several types of hormones. The expression of HMGR gene increased within several
      hours after hypergravity treatment. Also, compactin, an inhibitor of HMGR,
      prevented hypergravity-induced growth suppression, suggesting that HMGR is
      involved in suppression of Arabidopsis hypocotyl growth by hypergravity. In
      addition, hypergravity increased the expression levels of genes encoding CCR1 and
      ERD15, which were shown to take part in the signaling pathway of environmental
      stimuli such as temperature and water, and those of the alpha-tubulin gene. These
      genes may be involved in a series of cellular events leading to growth
      suppression of stem organs under hypergravity conditions.

PMID- 14686432
TI  - Touch and gravitropic set-point angle interact to modulate gravitropic growth in
      roots.
AB  - Plant roots must sense and respond to a variety of environmental stimuli as they
      grow through the soil. Touch and gravity represent two of the mechanical signals
      that roots must integrate to elicit the appropriate root growth patterns and root
      system architecture. Obstacles such as rocks will impede the general downwardly
      directed gravitropic growth of the root system and so these soil features must be
      sensed and this information processed for an appropriate alteration in
      gravitropic growth to allow the root to avoid the obstruction. We show that
      primary and lateral roots of Arabidopsis do appear to sense and respond to
      mechanical barriers placed in their path of growth in a qualitatively similar
      fashion. Both types of roots exhibited a differential growth response upon
      contacting the obstacle that directed the main axis of elongation parallel to the
      barrier. This growth habit was maintained until the obstacle was circumvented, at
      which point normal gravitropic growth was resumed. Thus, the gravitational set
      point angle of the primary and lateral roots prior to encountering the barrier
      were 95 degrees and 136 degrees respectively and after growing off the end of the
      obstacle identical set-point angles were reinstated. However, whilst tracking
      across the barrier, quantitative differences in response were observed between
      these two classes of roots. The root tip of the primary root maintained an angle
      of 136 degrees to the horizontal as it traversed the barrier whereas the lateral
      roots adopted an angle of 154 degrees. Thus, this root tip angle appeared
      dependent on the gravitropic set-point angle of the root type with the difference
      in tracking angle quantitatively reflecting differences in initial set-point
      angle. Concave and convex barriers were also used to analyze the response of the
      root to tracking along a continuously varying surface. The roots maintained the a
      fairly fixed angle to gravity on the curved surface implying a constant resetting
      of this tip angle/tracking response as the curve of the surface changed. We
      propose that the interaction of touch and gravity sensing/response systems
      combine to strictly control the tropic growth of the root. Such signal
      integration is likely a critical part of growth control in the stimulus-rich
      environment of the soil.

PMID- 14686433
TI  - Phytochromes play a role in phototropism and gravitropism in Arabidopsis roots.
AB  - Phototropism as well as gravitropism plays a role in the oriented growth of roots
      in flowering plants. In blue or white light, roots exhibit negative phototropism,
      but red light induces positive phototropism in Arabidopsis roots. Phytochrome A
      (phyA) and phyB mediate the positive red-light-based photoresponse in roots since
      single mutants (and the double phyAB mutant) were severely impaired in this
      response. In blue-light-based negative phototropism, phyA and phyAB (but not
      phyB) were inhibited in the response relative to the WT. In root gravitropism,
      phyB and phyAB (but not phyA) were inhibited in the response compared to the WT.
      The differences observed in tropistic responses were not due to growth
      limitations since the growth rates among all the mutants tested were not
      significantly different from that of the WT. Thus, our study shows that the blue
      light and red-light systems interact in roots and that phytochrome plays a key
      role in plant development by integrating multiple environmental stimuli.

PMID- 14686434
TI  - Oxygen requirement of germinating flax seeds.
AB  - Plant experiments in earth orbit are typically prepared on the ground and
      germinated in orbit to study gravity effects on the developing seedlings.
      Germination requires the breakdown of storage compounds, and this metabolism
      depends upon respiration, making oxygen one of the limiting factors in seed
      germination. In microgravity lack of run-off of excess water requires careful
      testing of water dispensation and oxygen availability. In preparation for a
      shuttle experiment (MICRO on STS-107) we studied germination and growth of flax
      (Linum usitatissimum L.) seedlings in the developed hardware (Magnetic Field
      Chamber, MFC). We tested between four to 32 seeds per chamber (air volume=14 mL)
      and after 36 h measured the root length. At 90 microliters O2 per seed (32
      seeds/chamber), the germination decreased from 94 to 69%, and the root length was
      reduced by 20%, compared to 8 seeds per chamber. Based on the percent germination
      and root length obtained in controlled gas mixtures between 3.6 and 21.6% O2 we
      determined the lower limit of reliable germination to be 10 vol. % O2 at
      atmospheric pressure. Although the oxygen available in the MFC's can support the
      intended number of seeds, the data show that seed storage and microgravity
      related limitations may reduce germination.

PMID- 14686435
TI  - The promotive effect of latrunculin B on maize root gravitropism is concentration
      dependent.
AB  - The cytoskeleton has been proposed to be a key player in the gravitropic response
      of higher plants. A major approach to determine the role of the cytoskeleton in
      gravitropism has been to use inhibitors to disrupt the cytoskeleton and then to
      observe the effect that such disruption has on organ bending. Several
      investigators have reported that actin or microtubule inhibitors do not prevent
      root gravitropism, leading to the conclusion that the cytoskeleton is not
      involved in this process. However, there are recent reports showing that
      disruption of the actin cytoskeleton with the actin inhibitor, latrunculin B,
      promotes the gravitropic response of both roots and shoots. In roots, curvature
      is sustained during prolonged periods of clinorotation despite short periods of
      gravistimulation. These results indicate that an early gravity-induced signal
      continues to persist despite withdrawal of the constant gravity stimulus. To
      investigate further the mechanisms underlying the promotive effect of actin
      disruption on root gravitropism, we treated maize roots with varying
      concentrations of latrunculin B in order to determine the lowest concentration of
      latrunculin B that has an effect on root bending. After a 10-minute
      gravistimulus, treated roots were axially rotated on a one rpm clinostat and
      curvature was measured after 15 hours. Our results show that 100 nM latrunculin B
      induced the strongest promotive effect on the curvature of maize roots grown on a
      clinostat. Moreover, continuously gravistimulated roots treated with 100 nM
      latrunculin B exhibited stronger curvature responses while decapped roots treated
      with this concentration of latrunculin B did not bend during continuous
      gravistimulation. The stronger promotive effect of low concentrations of
      latrunculin B on the curvature of both clinorotated and continuously
      gravistimulated roots suggests that disruption of the finer, more dynamic
      component of the actin cytoskeleton could be the cause of the enhanced tropic
      responses of roots to gravity.

PMID- 14686436
TI  - Microinjection--a tool to study gravitropism.
AB  - Despite extensive studies on plant gravitropism this phenomenon is still poorly
      understood. The separation of gravity sensing, signal transduction and response
      is a common concept but especially the mechanism of gravisensing remains unclear.
      This paper focuses on microinjection as powerful tool to investigate gravisensing
      in plants. We describe the microinjection of magnetic beads in rhizoids of the
      green alga Chara and related subsequent manipulation of the gravisensing system.
      After injection, an external magnet can control the movement of the magnetic
      beads. We demonstrate successful injection of magnetic beads into rhizoids and
      describe a multitude of experiments that can be carried out to investigate
      gravitropism in Chara rhizoids. In addition to examining mechanical properties,
      bead microinjection is also useful for probing the function of the cytoskeleton
      by coating beads with drugs that interfere with the cytoskeleton. The injection
      of fluorescently labeled beads or probes may reveal the involvement of the
      cytoskeleton during gravistimulation and response in living cells.

PMID- 14686437
TI  - Genetic analysis of the gravitropic set-point angle in lateral roots of
      Arabidopsis.
AB  - Research on gravity responses in plants has mostly focused on primary roots and
      shoots, which typically orient to a vertical orientation. However, the
      distribution of lateral organs and their characteristically non-vertical growth
      orientation are critical for the determination of plant form. For example, in
      Arabidopsis, when lateral roots emerge from the primary root, they grow at a
      nearly horizontal orientation. As they elongate, the roots slowly curve until
      they eventually reach a vertical orientation. The regulation of this lateral root
      orientation is an important component affecting overall root system architecture.
      We found that this change in orientation is not simply due to the onset of
      gravitropic competence, as non-vertical lateral roots are capable of both
      positive and negative gravitropism. Thus, the horizontal growth of new lateral
      roots appears to be determined by what is called the gravitropic set-point angle
      (GSA). This developmental control of the GSA of lateral roots in Arabidopsis
      provides a useful system for investigating the components involved in regulating
      gravitropic responses. Using this system, we have identified several Arabidopsis
      mutants that have altered lateral root orientations but maintain normal primary
      root orientation.

PMID- 14686438
TI  - Seed-to-seed growth of Arabidopsis thaliana on the International Space Station.
AB  - The assembly of the International Space Station (ISS) as a permanent experimental
      outpost has provided the opportunity for quality plant research in space. To take
      advantage of this orbital laboratory, engineers and scientists at the Wisconsin
      Center for Space Automation and Robotics (WCSAR), University of Wisconsin
      Madison, developed a plant growth facility capable of supporting plant growth in
      the microgravity environment. Utilizing this Advanced Astroculture (ADVASC) plant
      growth facility, an experiment was conducted with the objective to grow
      Arabidopsis thaliana plants from seed-to-seed on the ISS. Dry Arabidopsis seeds
      were anchored in the root tray of the ADVASC growth chamber. These seeds were
      successfully germinated from May 10 until the end of June 2001. Arabidopsis
      plants grew and completed a full life cycle in microgravity. This experiment
      demonstrated that ADVASC is capable of providing environment conditions suitable
      for plant growth and development in microgravity. The normal progression through
      the life cycle, as well as the postflight morphometric analyses, demonstrate that
      Arabidopsis thaliana does not require the presence of gravity for growth and
      development.

PMID- 14686439
TI  - High phosphorylase activity is correlated with increased potato minituber
      formation and starch content during extended clinorotation.
AB  - The major purpose of these experiments were to investigate growth of potato
      storage organs and starch synthesis in minitubers at slow horizontal
      clinorotation (2 rpm), which partly mimics microgravity, and a secondary goal was
      to study the activity and localization of phosphorylase (EC 2.4.1.1) in storage
      parenchyma under these conditions. Miniplants of Solanum tuberosum L. (cv Adreta)
      were grown in culture for 30 days for both the vertical control and the
      horizontal clinorotation. During long-term clinorotation, an acceleration of
      minituber formation, and an increase of amyloplast number and size in storage
      parenchyma cells, as well as increased starch content, was observed in the
      minitubers. The differences among cytochemical reaction intensity, activity of
      phosphorylase, and carbohydrate content in storage parenchyma cells of minitubers
      grown in a horizontal clinostat were established by electron-cytochemical and
      biochemical methods. It is shown that high phosphorylase activity is correlated
      with increased starch content during extended clinorotation. The results
      demonstrate the increase in carbohydrate metabolism and possible accelerated
      growth of storage organs under the influence of microgravity, as mimicked by
      clinorotation; therefore, clinorotation can be used as a basis for future studies
      on mechanisms of starch synthesis under microgravity.

PMID- 14686440
TI  - Comparative characteristic of mitochondria ultrastructural organization in
      Chlorella cells under altered gravity conditions.
AB  - Results from experiments that used cells from the unicellular alga Chlorella
      vulgaris (strain Larg-1) grown on a clinostat, demonstrated the occurrence of
      rearrangements in cellular organelles, including changes in the mitochondrial
      ultrastructure compared to controls. Changes in mitochondrial structure were
      observed in auto- and heterotrophic regimes of cells grown in altered gravity
      conditions, especially in long-term experiments. The mitochondrial rearrangements
      become apparent during cell proliferation, which resulted in an increase in the
      relative volume of mitochondria per cell: up to 2.7 +/- 0.3% in short-term clino
      rotation (2.2 +/- 0.1% in the control) and up to 5.3 +/- 0.4% and 5.1 +/- 0.4% in
      long-term clinorotation (2.3 +/- 0.2% in the control). The size of the
      mitochondria and their cristae increased in cells grown under long-time
      clinorotation. In addition, hypertrophied organelles, not typical for this
      strain, were observed. These changes in the cells were accompanied by increased
      electron density of the matrix and a well-ordered topography of the cristae. To
      examine the separation of oxidative phosphorylation and respiration, an
      inhibitory agent 2,4-dinitrophenol (2,4-DNP) was applied to cells which resulted
      in insignificant volume changes of the mitochondria (2.5 +/- 0.4% versus 2.1 +/-
      0.2% in the control). The increase of mitochondrial size with regularly arranged
      cristae, with more condensed matrix and extension of cristae areas of clino
      rotated cells, may demonstrate higher functional activity of the mitochondria
      under altered gravity conditions. Changes observed early in clinorotated cells,
      in particular the increased level of respiration, adenylate content (especially
      ATP) and more intensive electron-cytochemical reactions of Mg2(+)-ATPase and
      succinate [correction of succinat] dehydrogenase (SDH) in mitochondria (including
      hypertrophic organelles), also suggest increased activity of mitochondria from
      cells grown under altered gravity conditions compared to controls.

PMID- 14686441
TI  - Germination and elongation of flax in microgravity.
AB  - This experiment was conducted as part of a risk mitigation payload aboard the
      Space Shuttle Atlantis on STS-101. The objectives were to test a newly developed
      water delivery system, and to determine the optimal combination of water volume
      and substrate for the imbibition and germination of flax (Linum usitatissimum)
      seeds in space. Two different combinations of germination paper were tested for
      their ability to absorb, distribute, and retain water in microgravity. A single
      layer of thick germination paper was compared with one layer of thin germination
      paper under a layer of thick paper. Paper strips were cut to fit snugly into seed
      cassettes, and seeds were glued to them with the micropyle ends pointing outward.
      Water was delivered in small increments that traveled through the paper via
      capillary action. Three water delivery volumes were tested, with the largest (480
      microliters) outperforming the 400 microliters and 320 microliters volumes for
      percent germination (90.6%) and root growth (mean=4.1 mm) during the 34-hour
      spaceflight experiment. The ground control experiment yielded similar results,
      but with lower rates of germination (84.4%) and shorter root lengths (mean=2.8
      mm). It is not clear if the roots emerged more quickly in microgravity and/or
      grew faster than the ground controls. The single layer of thick germination paper
      generally exhibited better overall growth than the two layered option.
      Significant seed position effects were observed in both the flight and ground
      control experiments. Overall, the design of the water delivery system, seed
      cassettes and the germination paper strip concept was validated as an effective
      method for promoting seed germination and root growth under microgravity
      conditions.

PMID- 14686442
TI  - Growth restoration in azuki bean and maize seedlings by removal of hypergravity
      stimuli.
AB  - Hypergravity stimuli, gravitational acceleration of more than 1 x g, decrease the
      growth rate of azuki bean epicotyls and maize coleoptiles and mesocotyls by
      decreasing the cell wall extensibility via an increase in the molecular mass of
      matrix polysaccharides. An increase in the pH in the apoplastic fluid is
      hypothesized to be involved in the processes of the increase in the molecular
      mass of matrix polysaccharides due to hypergravity. However, whether such
      physiological changes by hypergravity are induced by normal physiological
      responses or caused by physiological damages have not been elucidated. In the
      present study, we examined the effects of the removal of hypergravity stimuli on
      growth and the cell wall properties of azuki bean and maize seedlings to clarify
      whether the effects of hypergravity stimuli on growth and the cell wall
      properties are reversible or irreversible. When the seedlings grown under
      hypergravity conditions at 300 x g for several hours were transferred to 1 x g
      conditions, the growth rate of azuki bean epicotyls and maize coleoptiles and
      mesocotyls greatly increased within a few hours. The recovery of growth rate of
      these organs was accompanied by an immediate increase in the cell wall
      extensibility, a decrease in the molecular mass of matrix polysaccharides, and an
      increase in matrix polysaccharide-degrading activities. The apoplastic pH also
      decreased promptly upon the removal of hypergravity stimuli. These results
      suggest that plants regulate the growth rate of shoots reversibly in response to
      hypergravity stimuli by changing the cell wall properties, by which they adapt
      themselves to different gravity conditions. This study also revealed that changes
      in growth and the cell wall properties under hypergravity conditions could be
      recognized as normal physiological responses of plants. In addition, the results
      suggest that the effects of microgravity on plant growth and cell wall properties
      should be reversible and could disappear promptly when plants are transferred
      from microgravity to 1 x g. Therefore, plant materials should be fixed or frozen
      on orbit for detecting microgravity-induced changes in physiological parameters
      after recovering the materials to earth in space experiments.

PMID- 14686443
TI  - Kinetics of amyloplast movement in cress root statocytes under different
      gravitational loads.
AB  - In order to investigate the movement of a statolith complex along the
      longitudinal axis of root cap statocytes under different mass accelerations, a
      series of experiments with Lepidium sativum L. in an automatically operating
      centrifuge during the Bion-11 satellite flight and on a centrifuge-clinostat have
      been performed. During spaceflight, roots were grown for 24 h under root-tip
      directed centrifugal 1-g acceleration, then exposed to microgravity for 6, 12 and
      24 min and chemically fixed. During the first 6 min of microgravity, the
      statoliths moved towards the cell center with a mean velocity of 0.31 +/- 0.04
      micrometers/min, which decreased to 0.12 +/- 0.01 micrometers/min within
      subsequent 12-24 min period. The mean relative position of the statolith complex
      in respect to the distal cell wall (% of total cell length) increased from 24.0
      +/- 0.5% in 1 g-grown roots to 38.8 +/- 0.8% in roots exposed for 24 min to
      microgravity, but remained smaller than in roots grown continuously in
      microgravity (48.0 +/- 0.7%). The properties of the statolith movement away from
      the distal pole of the statocyte were studied in roots grown for 24 h vertically
      under 1 g and then placed for 6 min on a fast rotating clinostat (50 rpm) or 180
      degrees inverted. After 2 min of both treatments, the mean relative position of
      the statoliths increased by about 10% versus its initial position. Later on, the
      proximal displacement of amyloplasts slowed down under simulated weightlessness,
      while it proceeded at a constant velocity under 1 g inversion. In roots grown on
      the clinostat and then exposed to 1 g in the longitudinal direction, amyloplast
      sedimentation away from the central region of statocyte was similar at the
      beginning of distal and proximal 6-min 1-g stimulation. However, at the end of
      this period statolith displacement was more pronounced in proximal direction as
      compared to distal. It is proposed that statolith position in the statocyte of a
      vertical root is controlled by the force of gravity, however, the intracellular
      forces, first of all those generated by the network of the cytoskeleton, are
      manifested when an usual orientation of the organ is changed or the statocytes
      are exposed to microgravity and clinorotation.

PMID- 14686445
TI  - Professor Michael J Hill (1939-2003).

PMID- 14686444
TI  - Changes in vacuolation in the root apex cells of soybean seedlings in
      microgravity.
AB  - Changes in the vacuolation in root apex cells of soybean (Glycine max L. [Merr.])
      seedlings grown in microgravity were investigated. Spaceflight and ground control
      seedlings were grown in the absence or presence of KMnO4 (to remove ethylene) for
      6 days. After landing, in order to study of cell ultrastructure and subcellular
      free calcium ion distribution, seedling root apices were fixed in 2.5% (w/v)
      glutaraldehyde in 0.1 M cacodylate buffer and 2% (w/v) glutaraldehyde, 2.5% (w/v)
      formaldehyde, 2% (w/v) potassium antimonate K[Sb(OH)6] in 0.1 M K2HPO4 buffer
      with an osmolarity (calculated theoretically) of 0.45 and 1.26 osmol. The
      concentrations of ethylene in all spaceflight canisters were significantly higher
      than in the ground control canisters. Seedling growth was reduced in the
      spaceflight-exposed plants. Additionally, the spaceflight-exposed plants
      exhibited progressive vacuolation in the root apex cells, particularly in the
      columella cells, to a greater degree than the ground controls. Plasmolysis was
      observed in columella cells of spaceflight roots fixed in solutions with
      relatively high osmolarity (1.26 osmol). The appearance of plasmolysis permitted
      the evaluation of the water status of cells. The water potential of the
      spaceflight cells was higher than the surrounding fixative solution. A decrease
      in osmotic potential and/or an increase in turgor potential may have induced
      increases in cell water potential. However, the plasmolysed (i.e. non-turgid)
      cells implied that increases in water potential were accompanied with a decrease
      in osmotic potential. In such cells changes in vacuolation may have been involved
      to maintain turgor pressure or may have been a result of intensification of other
      vacuolar functions like digestion and storage.

PMID- 14686446
TI  - Effects of prolonged bed rest on the total peripheral resistance baroreflex.
AB  - Orthostatic intolerance following prolonged exposure to microgravity continues to
      be a primary concern of the human space program. Reduced autonomic tone has been
      demonstrated to contribute to this phenomenon, and the heart rate baroreflex, in
      particular, has been repeatedly shown to be impaired. However, only the works of
      Yelle et al. have attempted to address the role of the total peripheral
      resistance (TPR) baroreflex, a potentially more significant contributor to blood
      pressure regulation. We applied a previously developed method for estimating the
      static gains of both the arterial and cardiopulmonary TPR baroreflexes to data
      obtained before and after 16-day bed rest. Reductions in the estimated static
      gains of the arterial (statistically significant) and cardiopulmonary TPR
      baroreflexes were found after bed rest. This study supports the works of Yelle et
      al, which imply that the TPR baroreflex is reduced after spaceflight.

PMID- 14686447
TI  - A geometric deformable model for echocardiographic image segmentation.
AB  - Gradient vector flow (GVF), an elegant external force for parametric deformable
      models, can capture object boundaries from both sides. A new geometric deformable
      model is proposed that combines GVF and the geodesic active contour model. The
      level set method is used as the numerical method of this model. The model is
      applied for echocardiographic image segmentation.

PMID- 14686448
TI  - Multiscale entropy to distinguish physiologic and synthetic RR time series.
AB  - We address the challenge of distinguishing physiologic interbeat interval time
      series from those generated by synthetic algorithms via a newly developed
      multiscale entropy method. Traditional measures of time series complexity only
      quantify the degree of regularity on a single time scale. However, many
      physiologic variables, such as heart rate, fluctuate in a very complex manner and
      present correlations over multiple time scales. We have proposed a new method to
      calculate multiscale entropy from complex signals. In order to distinguish
      between physiologic and synthetic time series, we first applied the method to a
      learning set of RR time series derived from healthy subjects. We empirically
      established selected criteria characterizing the entropy dependence on scale
      factor for these datasets. We then applied this algorithm to the CinC 2002 test
      datasets. Using only the multiscale entropy method, we correctly classified 48 of
      50 (96%) time series. In combination with Fourier spectral analysis, we correctly
      classified all time series.

PMID- 14686449
TI  - Simulate heart rate variability in different physiological conditions.
AB  - Heart rate variability is assumed to result from a multiplicative or cascade
      mechanism based on its multifractal property. Numerical results on the
      perturbation of the cascade are given to compare HRV under parasympathetic (PNS)
      and sympathetic (SNS) autonomic blockades. It was found that qualitative change
      of the HRV multifractal, which was observed in PNS blockade, is due to the change
      from a multiplicative to an additive mechanism.

PMID- 14686450
TI  - An automated, web-enabled and searchable database system for archiving
      electrogram and related data from implantable cardioverter defibrillators.
AB  - The advent of implantable cardioverter defibrillators (ICDs) has resulted in
      significant reductions in mortality in patients at high risk for sudden cardiac
      death. Extensive related basic research and clinical investigation continue. ICDs
      typically record intracardiac electrograms and inter-beat intervals along with
      device settings during episodes of device delivery of therapy. Researchers
      wishing to study these data further have until now been limited to viewing paper
      plots. In support of multi-center clinical studies of patients with ICDs, we have
      developed a web based searchable ICD data archiving system, which allows users to
      use a web browser to upload ICD data from diskettes to a server where the data
      are automatically processed and archived. Users can view and download the
      archived ICD data directly via the web. The entire system is built from open
      source software. At present more than 500 patient ICD data sets have been
      uploaded to and archived in the system. This project will be of value not only to
      those who wish to conduct research using ICD data, but also to clinicians who
      need to archive and review ICD data collected from their patients.

PMID- 14686451
TI  - Heart rate variability during gravity transitions.
AB  - During parabolic flight short periods of microgravity and hypergravity are
      created. During standing position time domain analysis showed higher vagal
      modulation of the autonomic nervous system in microgravity compared to
      hypergravity. We hypothesised that this behaviour could better be unravelled by
      analysis of frequency domain heart rate variability (HRV) techniques. During
      parabolic flights a subject is exposed to 20-25 sec periods of microgravity (at
      the top of the parabola), preceded and followed by 20 sec duration episodes of
      hypergravity. No significant differences were found in the frequency parameters
      in supine position for each of the phases. In standing position higher values for
      Total Power, high frequency (HF), low frequency (LF), LF/HF and HF% in 0 g phase
      were found in comparison with the 3 other phases. LF% was significant lower in
      standing position at 0 g compared with 1.8 g. These results show that despite the
      time window limitations, frequency analysis is still possible on ultra short data
      segments.

PMID- 14686452
TI  - Computer systems analysis of the cardiovascular mechanisms of reentry orthostasis
      in astronauts.
AB  - Reentry orthostasis secondary to a prolonged exposure to microgravity is a common
      problem among astronauts. However, the physiologic mechanisms are poorly
      understood due to the many control systems involved. In this study an advanced
      computer model of cardiovascular functioning was employed in a systems analysis
      approach to clarify the relative importance of some of the adaptive physiologic
      processes engaged when humans return from space. After simulation of the
      conditions of zero gravity for one month, the model predicted that the change in
      capacitance of the lower extremity veins resulting from a loss of external fluid
      forces in the dehydrated extracellular compartment was the dominant mechanism
      associated with reentry orthostasis. This condition appears accentuated in women
      due to their inherent lower center of gravity and proportionately larger mass in
      the lower extremities.

PMID- 14686453
TI  - A computational model-based validation of Guyton's analysis of cardiac output and
      venous return curves.
AB  - Guyton developed a popular approach for understanding the factors responsible for
      cardiac output (CO) regulation in which 1) the heart-lung unit and systemic
      circulation are independently characterized via CO and venous return (VR) curves,
      and 2) average CO and right atrial pressure (RAP) of the intact circulation are
      predicted by graphically intersecting the curves. However, this approach is
      virtually impossible to verify experimentally. We theoretically evaluated the
      approach with respect to a nonlinear, computational model of the pulsatile heart
      and circulation. We developed two sets of open circulation models to generate CO
      and VR curves, differing by the manner in which average RAP was varied. One set
      applied constant RAPs, while the other set applied pulsatile RAPs. Accurate
      prediction of intact, average CO and RAP was achieved only by intersecting the CO
      and VR curves generated with pulsatile RAPs because of the pulsatility and
      nonlinearity (e.g., systemic venous collapse) of the intact model. The CO and VR
      curves generated with pulsatile RAPs were also practically independent. This
      theoretical study therefore supports the validity of Guyton's graphical analysis.

PMID- 14686454
TI  - Fast interactive real-time volume rendering of real-time three-dimensional
      echocardiography: an implementation for low-end computers.
AB  - Real-time three-dimensional echocardiography (RT3DE) is an innovative cardiac
      imaging modality. However, partly due to lack of user-friendly software, RT3DE
      has not been widely accepted as a clinical tool. The object of this study was to
      develop and implement a fast and interactive volume renderer of RT3DE datasets
      designed for a clinical environment where speed and simplicity are not secondary
      to accuracy. Thirty-six patients (20 regurgitation, 8 normal, 8 cardiomyopathy)
      were imaged using RT3DE. Using our newly developed software, all 3D data sets
      were rendered in real-time throughout the cardiac cycle and assessment of cardiac
      function and pathology was performed for each case. The real-time interactive
      volume visualization system is user friendly and instantly provides consistent
      and reliable 3D images without expensive workstations or dedicated hardware. We
      believe that this novel tool can be used clinically for dynamic visualization of
      cardiac anatomy.

PMID- 14686455
TI  - MIMIC II: a massive temporal ICU patient database to support research in
      intelligent patient monitoring.
AB  - Development and evaluation of Intensive Care Unit (ICU) decision-support systems
      would be greatly facilitated by the availability of a large-scale ICU patient
      database. Following our previous efforts with the MIMIC (Multi-parameter
      Intelligent Monitoring for Intensive Care) Database, we have leveraged advances
      in networking and storage technologies to develop a far more massive temporal
      database, MIMIC II. MIMIC II is an ongoing effort: data is continuously and
      prospectively archived from all ICU patients in our hospital. MIMIC II now
      consists of over 800 ICU patient records including over 120 gigabytes of data and
      is growing. A customized archiving system was used to store continuously up to
      four waveforms and 30 different parameters from ICU patient monitors. An
      integrated user-friendly relational database was developed for browsing of
      patients' clinical information (lab results, fluid balance, medications, nurses'
      progress notes). Based upon its unprecedented size and scope, MIMIC II will prove
      to be an important resource for intelligent patient monitoring research, and will
      support efforts in medical data mining and knowledge-discovery.

PMID- 14686456
TI  - Different estimates of cardiac power: relationship to altered loading conditions.
AB  - Peak instantaneous power is a prognostic index of LV function but is difficult to
      measure. It is relatively load independent when corrected by preload (EDV2).
      Easier to acquire power estimates have been proposed--including mean and
      simplified power. These require only echo Doppler flow and cuff pressures, but
      their relationship to invasively derived results has not been studied. Using a
      well-validated numerical model of the cardiovascular system, different estimates
      of power were compared for varying preload, afterload, and contractility. All
      power results were divided by EDV2. Estimates of power correlate with peak power
      over a wide range of physiology. Corrected power estimates were independent of
      preload and afterload, but predictably increased with contractility. Different
      estimates of preload corrected power can be derived from non-invasively obtained
      variables and correlate with corrected peak instantaneous power.

PMID- 14686457
TI  - A qualitative research study of the evolution of symptoms in individuals
      identified as prodromal to psychosis.
AB  - Because schizophrenia is difficult to treat and exacts large personal and
      societal costs, there is an effort underway to identify adolescents and young
      adults at high risk for psychosis. Theory-derived criteria of subthreshold
      positive symptoms identify a "prodromal" or clinically at-risk population who
      have conversion rates to psychosis of 40 to 50% within one to two years. However,
      further characterization of the psychosis prodrome by qualitative research
      methods could increase the predictive value of the "prodromal" designation. We
      conducted open-ended interviews with 20 parents of prodromal adolescents that
      focused on changes observed. The narratives fell into two thematically distinct
      subgroups, identified as "declining" and "never normal." The prodromal
      adolescents described as "declining" had a higher subsequent rate of conversion
      to psychosis than did the "never normal" group. Although preliminary, these
      results suggest that a trajectory of change in personality, relationships, and
      behavior from an essentially normal baseline may be consistent with increased
      risk for psychosis among prodromal adolescents.

PMID- 14686458
TI  - Early intervention with traumatized children.
AB  - With the events of September 11th, childhood trauma has come to the forefront of
      national attention. One of the common psychiatric outcomes of trauma is
      Posttraumatic Stress Disorder (PTSD). Despite the fact that certain
      vulnerabilities may contribute to the development of PTSD in traumatized youth,
      the existence of an identifiable stressor provides a unique opportunity for early
      intervention. Cognitive Behavioral Treatment (CBT) interventions are considered
      by many to be the mainstay of treatment of children and adolescents with PTSD.
      More severe cases of PTSD are often treated with medications in the community. In
      this article we present a CBT program--developed by our site--STAIR--and provide
      useful guides and rationales for clinicians to work with when treating this
      population. We will also briefly review the available literature on the
      psychopharmacologic interventions to help guide the physician when confronted
      with such treatment decisions.

PMID- 14686459
TI  - Why are women diagnosed borderline more than men?
AB  - DSM-IV-TR states that borderline personality disorder (BPD) is "diagnosed
      predominantly (about 75%) in females." A 3:1 female to male gender ratio is quite
      pronounced for a mental disorder and, consequently, has led to speculation about
      its cause and to some empirical research. The essential question is whether the
      higher rate of BPD observed in women is a result of a sampling or diagnostic
      bias, or is it a reflection of biological or sociocultural differences between
      women and men? Data to address these issues are reviewed. The differential gender
      prevalence of BPD in clinical settings appears to be largely a function of
      sampling bias. True prevalence by gender is unknown. The modest empirical support
      for diagnostic biases of various kinds would not account for a wide difference in
      prevalence between the genders. Biological and sociocultural factors provide
      potentially illuminating hypotheses, should the true prevalence of BPD differ by
      gender.

PMID- 14686460
TI  - Adapting a substance abuse court diversion model for felony offenders with co
      occurring disorders: initial implementation.
AB  - Treatment Alternatives for Dually Diagnosed (TADD) was developed to address the
      need for criminal justice diversion of seriously mentally ill substance-using
      felons and persistent misdemeanants. The population served by the TADD program
      and key elements of the program are described, including identification,
      screening and assessment, specialized court processing and judicial oversight,
      case management monitoring, joint case conferencing between community and
      monitoring staff, enforcement, and key stakeholder collaboration. One hundred and
      thirteen clients diverted by the TADD program were followed for six months. A
      description is provided of these clients, the community services accessed, as
      well as the monitoring of clients drug use. During six months of program
      involvement 87% remained connected to the diversion team, 80% remained in
      community treatment and the majority took advantage of the rich service
      environment created through TADD's case management linkage services. The majority
      of these clients tested drug-free during this six-month period.

PMID- 14686461
TI  - Evidence-based medicine and psychiatric practice.
AB  - Evidence-based medicine (EBM) has been defined as "the conscientious, explicit
      and judicious use of current best evidence in making decisions about the care of
      individual patients." EBM requires the ability to apply a knowledge of medical
      informatics (e.g., efficiently searching the medical literature) and clinical
      epidemiology (e.g., being able to critically appraise the literature) to the
      treatment of individual patients. This article provides an introduction to the
      history, philosophy, and methods of EBM as applied to psychiatric practice. The
      article summarizes the five-step EBM model: (1) formulate the question; (2)
      search for answers; (3) appraise the evidence; (4) apply the results; and (5)
      assess the outcome. Resources (including Web sites) for further learning are
      provided.

PMID- 14686462
TI  - Contextualizing trauma: using evidence-based treatments in a multicultural
      community after 9/11.
AB  - The mental health community was caught unaware after 9/11 with respect to
      treatment of survivors of terrorist attacks. Because this form of trauma was
      quite rare in the U.S., few trauma specialists had extensive experience, or
      taught regularly on this subject. Since the primary objective of terrorism is the
      creation of demoralization, fear, and uncertainty in the general population, a
      focus on mental health from therapeutic and public health perspectives is
      critically important to successful resolution of the crisis. Surveys after 9/11
      showed unequivocally that symptomatology related to the attacks were found in
      hundreds of thousands of people, most of whom were not escapees or the families
      of the deceased. Soon after 9/11, our center formed a collaboration with other
      academic sites in Manhattan to rapidly increase capacity for providing state-of
      the-art training and treatment for trauma-related psychiatric problems. Our
      experience suggests that evidence-based treatments such as Prolonged Exposure
      Therapy have proven successful in treating 9/11-related PTSD. However, special
      clinical issues have arisen, such as the influence of culture on clinical
      presentation and treatment expectations in a multiethnic community; the need to
      focus on more subtle aspects of relative risk appraisal in examining trauma
      related avoidance; the range of changes in daily life that constitute adaptation
      to ongoing threat; the difficulties in working as a therapist who is also a
      member of the traumatized community; and grappling with multiple secondary
      consequences of 9/11 such as unemployment, work relocation, grief, and
      apocalyptic fears leading to a dramatically foreshortened vision of the future.

PMID- 14686463
TI  - Complications in pain management.

PMID- 14686464
TI  - What is the role of the hospice physician?

PMID- 14686465
TI  - Pain and symptom control in patients with advanced cancer.

PMID- 14686466
TI  - Drug therapy for cancer pain.

PMID- 14686468
TI  - Reaction to Hospice World View series.

PMID- 14686467
TI  - Symptom control in patients with advanced cancer.

PMID- 14686469
TI  - Comment on JCAHO hospice accreditation decision.

PMID- 14686470
TI  - Letter for hospice board members helpful.

PMID- 14686471
TI  - Non-pharmacologic measures for controlling oncologic pain.

PMID- 14686472
TI  - Pain control in hospice home care: management guidelines.

PMID- 14686473
TI  - Patients' perceptions of a community volunteer support program.

PMID- 14686474
TI  - Vesicular glutamate transporters in the brain.
AB  - Glutamate is an excitatory amino acid that acts as a major neurotransmitter
      throughout the brain. Although its neurotransmitter action has been evidenced by
      the identification of various receptor subtypes at synapses, a cellular mechanism
      by which this amino acid accumulates in synaptic vesicles has long been in doubt
      until the discovery in recent years of specific vesicular transporters. Three
      kinds of transporter isoforms have so far been cloned and their transport
      properties and distribution in the brain have been studied extensively. In
      contrast with the apparently similar ability of all transporter isoforms to
      highly selectively transport glutamate and their presence in synaptic vesicles,
      their regional distribution of gene expression and immunoreactivity in the rodent
      or human brain are surprisingly different from one another. This indicates that
      the glutamatergic neuron system of mammalian brains is substantially comprised of
      at least three different neuron subpopulations, each of which uses a unique
      transport system for the vesicular storage of glutamate. Thus, we now have highly
      useful and reliable tools for a comprehensive understanding of the glutamatergic
      neuron system in the brain from a new viewpoint different from that of other
      components, such as receptors. The scope of the present review is to provide an
      overview of the history and present status of the study of vesicular glutamate
      transporters and to highlight some unresolved issues requiring clarification for
      the progress of future brain function research.

PMID- 14686475
TI  - Identification of sour-taste receptor genes.
AB  - Taste cells located in taste buds respond to gustatory stimuli using a complex
      arrangement of ion channels, receptor molecules and signaling cascades. Previous
      electrophysiological experiments have shown that sour taste (essentially a taste
      of protons) is mediated, at least in part, by apically located amiloride
      sensitive channels in the rat. Here, the molecular cloning of sour-taste receptor
      genes is described. Using a combination of homology screening and functional
      expression approaches, we screened a rat circumvallate papilla cDNA library and
      identified acid-sensing ion channel-2a (ASIC2a) and ASIC2b, amiloride-sensitive
      proton-activated cation channels. In situ hybridization and reverse transcription
      polymerase chain reaction experiments showed that ASIC2a and ASIC2b transcripts
      were localized in taste cells. Immunohistochemical and immunoprecipitation
      studies revealed that both channels were expressed in a subset of taste cells and
      that some of the cells expressed ASIC2a/ASIC2b heteromeric assemblies.
      Immunoelectron microscopic analyses demonstrated that some of the ASIC2a
      immunopositive cells had the characteristics of type III cells, which make
      synaptic contacts with gustatory afferent neurons. According to our
      electrophysiological studies, stimulation by acetic acid generated larger inward
      currents in ASIC2a- or ASIC2a/ASIC2b-expressing oocytes than those induced by
      hydrochloric acid at the same proton concentration and these findings are in good
      agreement with the well-known taste phenomenon that acetic acid is more sour than
      hydrochloric acid at equal pH. Taken together, the present results strongly
      suggest that mucosal protons dissociated from sour-taste substances induce taste
      cell depolarization through the activation of the ASIC2a and ASIC2a/ASIC2b
      channels, which leads to transmitter release onto gustatory neurons.

PMID- 14686476
TI  - Gaps and fragmentation of the superficial cortex in the abdominal and pelvic
      lymph nodes of elderly Japanese.
AB  - Gaps and fragmentation of the superficial lymph node cortex are considered to
      provide intranodal shunt flow between the afferent and efferent vessels. Using
      serial sections of 205 nodes obtained from 27 donated cadavers more than 70 years
      of age, we examined the histological architecture of the abdominal and pelvic
      nodes in elderly Japanese. Secondary follicles were rare in the specimens. Cortex
      gaps were, to a greater or lesser degree, found in all nodes. We classified these
      nodes into three types according to how often the gap occurred. Type 1 nodes,
      with a relatively complete shield for the afferent lymph, were most frequently
      found in gastric nodes, whereas type 3 nodes, with numerous gaps, were often
      observed in the colic, para-aortic and pelvic nodes. The type 3 nodes showed a
      specific architecture characterized by a fragmented superficial cortex, three
      dimensionally assembled cords and a common sinus between them. Primary follicles
      were located in the assembled cord structures as well as at the superficial
      cortex. Irrespective of the type, B and T lymphocyte areas were intermingled in
      the cortex-like areas. The present results reveal region-specific histological
      heterogeneity in aged human visceral nodes. Due to increased surface areas, the
      type 3 architecture seemed to accelerate systemic immunity rather than act as a
      local barrier in the para-aortic and pelvic nodes, which are located centrally
      along the lymphatic drainage routes. However, thick trabeculae often seemed to
      develop in the type 3 sinus to decrease nodal function with aging.

PMID- 14686477
TI  - Histologic findings in left ventricle papillary muscle arteries from human
      hearts.
AB  - We describe original histologic findings of left ventricle papillary muscle
      (LVPM) arteries in people under 30 years of age. We examined 666 samples taken
      from the tip, mid-portion and base of papillary muscles in 56 males and 55
      females, as well as several samples from the rest of the left ventricle. The
      number of smooth muscle cells (SMC) in the tunica media of the LVPM arteries led
      us to divide the samples examined into three groups: (i) group 1, 355 samples
      (53%) with a normal number of SMC and a normal lumen (the number of group 1
      samples increased from the tip (21%) to the base (47%)); (ii) group 2, 252
      samples (38%) with a mild to moderately increased number of SMC (the number of
      these samples decreased from the tip (44%) to the base (22%)); and (iii) group 3,
      59 samples (9%) with abundant SMC that were more than twofold greater in size and
      number of normal arteries, in contrast with the other two groups. The shape of
      the SMC in group 3 samples was round and the extremely narrow, centrally located
      lumen of these SMCE had a round or oval shape. These changes were restricted only
      to papillary muscle arteries and the number of group 3 samples decreased from the
      tip (63%) to the mid-portion (37%). No inflammatory reaction or chronic ischemic
      changes were found in the LVPM arteries and surrounding area. The SMC changes in
      groups 2 and 3 were found in subjects aged more than 2 months. These findings
      will provide anatomists, cardiologists, pathologists and physiologists with
      valuable knowledge and will trigger further investigation into the etiology of
      the structural changes observed and their evolution with age.

PMID- 14686478
TI  - Fascial structures and autonomic nerves in the female pelvis: a study using
      macroscopic slices and their corresponding histology.
AB  - We investigated the topographical anatomy of the pelvic fasciae and autonomic
      nerves using macroscopic slices of five decalcified female pelves. The lateral
      aspect of the supravaginal cervix uteri and superior-most vagina issued abundant
      thick fiber bundles. These visceral fibrous tissues extended dorsolaterally,
      joined another fibrous tissue from the rectum (the actual lateral ligament of the
      rectum) and attached to the parietal fibrous tissues at and around the sciatic
      foramina (i.e. the sacrospinous ligament, thick fasciae of the coccygeus and
      piriformis and dorsal end of the covering fascia of the levator ani). The
      inferior or ventral vagina also issued thick fiber bundles communicating with the
      levator ani fascia. This connection between the vagina and levator fascia, when
      stretched, seemed to provide a macroscopic morphology called the arcus tendineus
      fasciae pelvis. The overall morphology of the visceroparietal fascial bridge
      exhibited a bilateral wing-like shape. The fascial bridge complex was adjacent
      but dorso-inferior to the internal iliac vascular sheath and located slightly
      ventral to the pelvic splanchnic nerve. However, the pelvic plexus and its
      peripheral branches were embedded in the fascial complex. The hypogastric nerve
      ran along and beneath the uterosacral peritoneal fold, which did not contain
      thick fibrous tissue. During surgery, in combination with the superficially
      located vascular sheath, the morphology of the visceroparietal fascial bridge and
      associated nerves seemed to be artificially changed and developed into the so
      called cardinal, uterosacral, uterovesical and/or rectal lateral ligaments. The
      classical and original concepts of these pelvic fascial structures may need to be
      altered to adjust to these surgical observations.

PMID- 14686479
TI  - Paraoxonase activity and genetic polymorphisms in greenhouse workers with long
      term pesticide exposure.
AB  - Serum paraoxonase (PON1) is a high-density lipoprotein (HDL) associated protein,
      which plays a critical role in the pathogenesis of atherosclerosis, although it
      was primarily associated with the hydrolysis of organophosphorus compounds. PON1
      was initially thought to be independent from physiological or pathological
      states, although recently some environmental factors have been reported to
      modulate its activity. In this study, we have investigated the promoter (PON1 
      108C/T and -909 C/G) and coding region (PON1 192Q/R and 55L/M) polymorphisms, as
      well as PON1 activity towards different substrates (paraoxon, phenylacetate and
      diazoxon) in 102 individuals with long term low dose exposure to pesticides in a
      plastic greenhouse setting (sprayers), who are probably the group of agricultural
      workers with the highest exposure to pesticides. PON1 activity towards paraoxon
      was nonsignificantly decreased (up to 53.5%) in the sprayers subgroup exposed to
      organophosphates (n = 41) compared with nonsprayers acting as controls (n = 39).
      None of the genotypes studied was associated significantly with the subgroup of
      individuals exposed to organophosphates, although differences between sprayers
      and nonsprayers were observed in the PON1 -909 G/C polymorphism. Among the
      environmental factors that significantly predicted lower rates of PON1 activity
      towards paraoxon are, interestingly, the exposure to organophosphates and current
      smoking. By contrast, the utilization of protective clothing while spraying
      pesticides inside the greenhouses was positively associated with PON1 activity,
      very likely by preventing the pesticides from being absorbed. This study suggests
      that chronic exposure to pesticides might decrease PON1 activity and pinpoints
      the potential usefulness of monitoring PON1 activity in occupational settings
      where exposure to organophosphates occurs.

PMID- 14686480
TI  - Statistical evaluation of the fixed concentration procedure for acute inhalation
      toxicity assessment.
AB  - The conventional method for the assessment of acute inhalation toxicity (OECD
      Test Guideline 403, 1981) uses death of animals as an endpoint to identify the
      median lethal concentration (LC50). A new OECD Testing Guideline called the Fixed
      Concentration Procedure (FCP) is being prepared to provide an alternative to Test
      Guideline 403. Unlike Test Guideline 403, the FCP does not provide a point
      estimate of the LC50 but aims to identify an airborne exposure level that causes
      clear signs of nonlethal toxicity. This is then used to assign classification
      according to the new Globally Harmonized System of Classification and Labelling
      scheme (GHS). The FCP has been validated using statistical simulation rather than
      by in vivo testing. The statistical simulation approach predicts the GHS
      classification outcome and the numbers of deaths and animals used in the test for
      imaginary substances with a range of LC50 values and dose-response curve slopes.
      This paper describes the FCP and reports the results from the statistical
      simulation study assessing its properties. It is shown that the procedure will be
      completed with considerably less death and suffering than Test Guideline 403, and
      will classify substances either in the same or a more stringent GHS class than
      that assigned on the basis of the LC50 value.

PMID- 14686481
TI  - Protection by sildenafil and theophylline of lead acetate-induced oxidative
      stress in rat submandibular gland and saliva.
AB  - The role of oxidative stress in lead toxicity has been proposed in many organs,
      however, no study has been performed in the salivary glands, which are important
      parts of the gastrointestinal tract with a high implication in health of the
      whole body. Recently, it has been proposed that increasing the levels of cGMP and
      cAMP in the cells may protect from the neurotoxicity of lead. The objective of
      this study was to determine the ability of lead acetate to produce oxidative
      stress in rat submandibular as the main salivary gland of the body and to study
      the role of pretreatment by specific phosphodiesterase inhibitors in the
      prevention of oxidative stress. Lead acetate (100 mg/kg), alone or in combination
      with theophylline (25 mg/kg) and sildenafil (5 mg/kg), was administered
      intraperitoneally to rats. After 2 hours and under general anaesthesia, the
      submandibular gland ducts were cannulated intraorally using microcannula, and
      pure saliva was collected for 30 min using pilocarpine (8 mg/kg) as a
      secretagogue. The submandibular glands were then isolated free under surgery.
      Oxidative stress in the gland and pure saliva were evaluated measuring lipid
      peroxidation (thiobarbituric acid reactive substances assay), total thiol groups
      content and total antioxidant capacity (the ferric reducing ability assay).
      Results showed significant oxidative stress in the gland and secretions as
      indicated by increased lipid peroxidation, decreased total antioxidant capacity
      and thiol group levels. The use of cAMP and cGMP phosodiesterase inhibitors,
      theophylline and sildenafil, prevented lead-induced increased lipid peroxidation
      and also protected from decreased thiol groups content and total antioxidant
      power of the gland and secretions. The same trend of effects was observed in
      gland and saliva. It is concluded that lead toxicity is mediated through
      oxidative stress in salivary glands, while increasing intracellular cAMP and cGMP
      levels may prevent lead-induced oxidative stress.

PMID- 14686482
TI  - The development of tolerance to Clostridium perfringens type D epsilon-toxin in
      MDCK and G-402 cells.
AB  - The epithelial Madin Darby canine kidney (MDCK) cell line, Caucasian renal
      leiomyoblastoma (G-402) cells, human small airways epithelial (HSAE) cells, human
      bronchial epithelial (HBE) cells and human renal proximal tubule (HRPT)
      epithelial cells were examined for sensitivity to Clostridium perfringens biotype
      D epsilon-toxin. MDCK and G-402 cells were confirmed as being the only
      established cell lines that are sensitive to the toxin. HSAE, HBE and HRPT
      epithelial cells were only found to be sensitive to the toxin at concentrations
      of > 1 mg/ mL. Cultures of MDCK and G-402 cells, with increased resistance
      (tolerance) to the cytotoxic effects of epsilon-toxin, were developed by exposing
      these cultures to progressively higher concentrations of toxin. The greatest
      relative increase in tolerance to epsilon-toxin was developed in MDCK cells, in
      which the LC50 in control cultures was 2 microg/mL as determined by the MTS/PMS
      assay system; after selection for tolerance, this was raised to 100 microg/mL.
      This represents a 50-fold increase in tolerance as measured by this index. Using
      G-402 cells, it was possible to increase the LC50 by twofold from 290 to 590
      microg/mL. Subsequent 2-D electrophoresis of membrane preparations from tolerant
      and control MDCK cells revealed that the expression of a discrete group of
      proteins found in control cells with a range of molecular weights from 32-36 kDa,
      all with acidic isoelectric points (IEPs), were either not expressed in epsilon
      toxin tolerant cells or had undergone a shift in IEP to a more alkaline pH in
      tolerant cells. This suggests that epsilon-toxin lethality in MDCK cells may be
      mediated by membrane-located proteins. Their absence or alteration in toxin
      resistant cells would, at least partly, explain the failure of most cell lines to
      demonstrate sensitivity to this toxin, despite being derived from tissues that
      are damaged by epsilon-toxin. This approach may have utility in the study of
      other toxin-cell interactions and could be used in the development of novel
      medical countermeasures by identifying cellular targets which mediate toxin
      lethality.

PMID- 14686483
TI  - In vitro studies on the toxicity of isoniazid in different cell lines.
AB  - The aim of the present study was to investigate in vitro the mechanism of
      toxicity of isoniazid (= INH), the drug most widely used for treatment of
      tuberculosis. The human hepatoma line HepG2, the human lymphoblastoid line AHH-1
      and the murine lymphoma cells YAC-1 were used as test systems. Active cell death
      (= apoptosis) and necrosis were detected by different flow cytometric methods:
      the binding of annexin V to the cell membrane and staining with propidium iodide
      (PI), the TUNEL assay for detection of DNA fragmentation and the occurrence of a
      sub G1 peak in cell cycle histograms. Mitochondrial membrane potential was
      analysed with the fluorescent probe JC-1. In addition to cytotoxicity, effects of
      INH on cell cycle were studied in HepG2 cells. The data of the present
      investigations indicate that INH induces cytotoxicity via apoptosis both in
      hepatoma and lymphoma cells. Twenty-four hours of application of INH in
      concentrations > 26 mM led to a remarkable number of apoptotic cells positive for
      Annexin V. The induction of apoptosis was accompanied by a break down of the
      mitochondrial membrane potential and the occurrence of DNA strand breaks. At
      incubation times from 36 to 48 hours, a sub-G1 peak of late apoptotic cells was
      detected in cell cycle analysis. Furthermore, cell cycle studies showed a
      disruption of the cycle at low concentrations of INH which are only mildly
      cytotoxic. Thus the present study unequivocally demonstrated that INH induces
      cytotoxicity via apoptosis and can lead to a significant disturbance of the cell
      cycle in mammalian cells.

PMID- 14686484
TI  - Prothrombin time prolongation in paracetamol poisoning: a relevant marker of
      hepatic failure?
AB  - The association between paracetamol overdose and prolonged prothrombin time due
      to hepatic failure is well recognized. However, little is known of the
      possibility that paracetamol overdose can prolong the prothrombin time without
      overt hepatic failure. The few data from the literature suggest this is either
      due to a reduction in the functional levels of the vitamin K-dependent clotting
      factors by elevated doses of paracetamol, or a consequence of the administration
      of the antidote N-acetylcystein. The three reported cases provide further
      evidence that paracetamol overdose can be associated with a prolongation in the
      prothrombin time without overt hepatic failure. Even though the prothrombin time
      provides useful prognosis information, decisions regarding the management of
      these patients should not solely be based on this endpoint to avoid
      misinterpretation of the accuracy and the severity of liver failure.

PMID- 14686486
TI  - Human T-lymphotropic virus type 1 (HTLV-1): persistence and immune control.
AB  - The human retrovirus human T-lymphotropic virus type 1 (HTLV-1) is associated
      with two distinct types of disease: the malignancy known as adult T-cell leukemia
      and a range of chronic inflammatory conditions including the central nervous
      system disease HTLV-1-associated myelopathy/tropical spastic paraparesis
      (HAM/TSP). Until recently, it was believed that HTLV-1 was largely latent in
      vivo. However, evidence from a number of types of experiments shows that HTLV-1
      persistently expresses its genes, and that the "set point" of an individual's
      proviral load of HTLV-1 is mainly determined by the efficiency of that
      individual's cellular immune response to the virus. These conclusions have two
      main consequences. First, HTLV-1 may be vulnerable to antiretroviral drug therapy
      or immunotherapy. Second, HTLV-1 infection has become a useful system to analyze
      the determinants of the efficiency of the antiviral immune response.

PMID- 14686487
TI  - Current status of therapeutic approaches to adult T-cell leukemia.
AB  - More than 2 decades have elapsed since the proposal of adult T-cell leukemia
      (ATL). Since then, the discovery of the etiologic virus, human T-cell leukemia
      virus type I (HTLV-I), and the establishment of the diagnostic steps of serum
      test and molecular study have clearly defined ATL as a distinct disease entity.
      Because conventional chemotherapy, which is active against other lymphoid
      malignancies, was proven to be ineffective for treating aggressive forms of ATL,
      ATL has become the target of several clinical studies for the purpose of
      improving therapeutic outcomes. Combination chemotherapy exclusively designed for
      ATL has considerably elevated the treatment response rate in ATL patients, but it
      has not sufficiently extended the median survival time. The introduction of
      antiviral agents has led to surprising effects for patients with acute ATL.
      Monoclonal antibodies seem to be promising, especially for patients with
      chemotherapy-resistant disease. Unfortunately, these approaches did not prove to
      be sufficient for most patients with ATL to obtain long-term survival. Recent
      promising reports on allogeneic stem cell transplantation (allo-SCT) for ATL have
      suggested that allo-SCT could overcome the limitations that other treatment
      modalities have not surmounted. More efforts are clearly needed to clarify the
      usefulness of allo-SCT, especially with reduced-intensity conditioning regimens,
      for ATL patients.

PMID- 14686485
TI  - T-cell control by human T-cell leukemia/lymphoma virus type 1.
AB  - Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) causes neoplastic
      transformation of human T-cells in a small number of infected individuals several
      years from infection. Collective evidence from in vitro studies indicates that
      several viral proteins act in concert to increase the responsiveness of T-cells
      to extracellular stimulation, modulate proapoptotic and antiapoptotic gene
      signals, enhance T-cell survival, and avoid immune recognition of the infected T
      cells. The virus promotes T-cell proliferation by usurping several signaling
      pathways central to immune T-cell function, such as antigen stimulation and
      receptor-ligand interaction, suggesting that extracellular signals are important
      for HTLV-1 oncogenesis. Environmental factors such as chronic antigen stimulation
      may therefore be of importance, as also suggested by epidemiological data. Thus
      genetic and environmental factors together with the virus contribute to disease
      development. This review focuses on current knowledge of the mechanisms
      regulating HTLV-1 replication and the T-cell pathways that are usurped by viral
      proteins to induce and maintain clonal proliferation of infected T-cells. The
      relevance of these laboratory findings is related to clonal T-cell proliferation
      and adult T-cell leukemia/lymphoma development in vivo.

PMID- 14686488
TI  - Leukemogenesis of adult T-cell leukemia.
AB  - Adult T-cell leukemia (ATL) is one of the most aggressive hematologic
      malignancies and is caused by human T-cell leukemia virus type I (HTLV-I). Tax,
      encoded by the HTLV-I pX region, has been recognized by its pleiotropic actions
      as a critical accessory protein playing a central role in leukemogenesis.
      However, fresh ATL cells frequently lose Tax protein expression via several
      mechanisms, such as genetic and epigenetic changes in the provirus. Furthermore,
      there is a long latency period before the onset of ATL, indicating the multistep
      mechanisms of leukemogenesis. Therefore, additional factors, including other
      viral proteins, genetic and epigenetic changes of the host genome, and
      alterations in the gene expression and immune systems of the host cells, may be
      implicated in ATL leukemogenesis. This review summarizes recent advances in the
      understanding of ATL leukemogenesis.

PMID- 14686489
TI  - Immunology of B7-H1 and its roles in human diseases.
AB  - B7-H1 was originally identified by homology analysis in comparison with B7-1 and
      B7-2, two molecules with important immunoregulatory functions. B7-H1, however,
      was broadly induced in the majority of peripheral tissues as well as
      hematopoietic cells. Upon binding to an as yet unidentified costimulatory
      receptor on primed T-cells, B7-H1 costimulates T-cell proliferation and
      preferentially induces interleukin 10 and interferon gamma. The costimulatory
      function of B7-H1 may be critical for enhancing maturation and differentiation of
      T-cells in lymphoid organs. Conversely, by binding to programmed death 1
      receptors on activated T-cells and B-cells, B7-H1 may inhibit ongoing T-cell
      responses in peripheral tissues by inducing apoptosis and arresting cell-cycle
      progression. Although a positive regulatory role of B7-H1 has been demonstrated
      in vitro and in various animal models, a negative regulatory role of B7-H1 has
      also been documented in human diseases, including cancer, rheumatoid arthritis,
      and human immunodeficiency virus infection. Delineation of the complex
      interactions between B7-H1 and its receptors as well as its interplay with other
      ligands is critical for understanding this new immunoregulatory system. Precise
      manipulation of B7-H1 and its receptors may provide unique opportunities for
      designing new disease treatments.

PMID- 14686490
TI  - Dominant beta-thalassemia with hemoglobin Hradec Kralove: enhanced hemolysis in
      the spleen.
AB  - We describe a 6-year-old girl and her mother with dominant beta-thalassemia due
      to hemoglobin Hradec Kralove (Hb HK). Both patients presented microcytic anemia,
      jaundice, splenomegaly, cholelithiasis, and recurrent hemolytic bouts. Osmotic
      resistance tests using saline and coiled planet centrifugation revealed the
      increased fragility of the red cell membrane. On the other hand, the glycerol
      lysing time was prolonged, and results of the isopropanol test were weakly
      positive. Despite mimicking the features of hereditary spherocytosis, the results
      of the genetic analyses verified the second reported family with Hb HK (codon
      115, GCC [Ala] --> GAC [Asp]). Splenectomy was effective for the amelioration of
      hemolysis. Of 7 reported patients with Hb variants at beta-globin codon 115 (Hb
      Madrid and Hb HK), 5 underwent splenectomy. Because of the variable augmentation
      of extramedullary hemolysis in dominant beta-thalassemias, genotyping is
      necessary for determining the clinical indication of splenectomy.

PMID- 14686491
TI  - Rituximab treatment for relapsed autoimmune hemolytic anemia in Evans syndrome.
AB  - A case is reported of idiopathic relapsed autoimmune hemolytic anemia
      successfully treated with rituximab. A 43-year-old white male patient with past
      medical history of Evans syndrome was found to have recurrent autoimmune
      hemolytic anemia. Previous treatments included steroids, splenectomy, intravenous
      immunoglobulin, plasmapheresis, staphylococcal Protein A immunoadsorption
      (Prosorba column), and chemotherapeutic agents (cytoxan and vincristine).
      Rituximab was given weekly at 375 mg/m2 for 4 doses. The drug was well tolerated
      and the patient remains in remission 9 months after completion of therapy.

PMID- 14686492
TI  - Immunophenotypes and outcome of Philadelphia chromosome-positive and -negative
      Thai adult acute lymphoblastic leukemia.
AB  - Little evidence exists in Asian countries regarding the incidence, immunologic
      characteristics, and clinical outcomes of adult patients with Philadelphia
      chromosome-positive (Ph+) and -negative (Ph-) acute lymphoblastic leukemia (ALL).
      In this study, we prospectively studied 324 Thai adult acute leukemia patients,
      79 (24%) of whom were identified as having ALL. Immunophenotyping was performed
      by 5-parameter flow cytometry, and karyotyping was conducted by standard banding
      methods. The Ph chromosome was detected in 18.5% of cases. The mean age of Ph+
      ALL patients was 29 years (50% male), and that of Ph- ALL patients was 33 years
      (62% female). The Ph+ ALL patients had significantly higher white blood cell
      (WBC) counts (mean, 93 x 10(9)/L), with 67% having WBC counts higher than 50 x
      10(9)/L. In contrast, most Ph- ALL patients had WBC counts lower than 50 x
      10(9)/L (mean, 36 x 10(9)/L; P < .05). CD10 and CD34 were more highly expressed
      in the Ph+ ALL patients (mean expression, 83% and 87%, respectively) than in the
      Ph- ALL patients (45% and 57%; P < .005). The aberrant expression of myeloid
      antigens, including CD33 and CD13, was also significantly observed in the Ph+ ALL
      patients. The median survival time of Ph+ ALL patients was 8 months, compared
      with 22 months for the Ph- ALL patients. In conclusion, immunophenotyping results
      showed that Ph+ ALL in Thai adults arises from B-cells at an earlier stage of
      development. Extreme leukocytosis, a younger age, male sex, high expression
      levels of CD10 and CD34, aberrant myeloid antigens, and poorer rates of survival
      appeared to be associated with the Ph chromosome in Thai adult ALL cases. The
      incidence of the Ph chromosome among Thai adult ALL patients was not different
      from that found in Western countries.

PMID- 14686493
TI  - Unusual association between increased bone resorption and presence of paroxysmal
      nocturnal hemoglobinuria phenotype in multiple myeloma.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) clones deficient in
      glycosylphosphatidylinositol-anchored molecules, including CD55 and CD59, have
      been previously described in patients with multiple myeloma (MM). The aim of this
      study was to investigate the possible association between existence of the PNH
      phenotype and myeloma bone disease. Forty-three patients with newly diagnosed MM
      were the subjects of the study. Radiographic evaluation of the skeleton was
      performed in all patients at diagnosis. The following biochemical markers were
      measured: bone resorption markers (tartrate-resistant acid phosphatase isoform 5b
      [TRACP-5b]and N-terminal cross-linking telopeptide of type-I collagen [NTX]),
      bone formation markers (bone alkaline phosphatase [bALP] and osteocalcin [OC]),
      osteoprotegerin (OPG), soluble receptor activator of nuclear factor KB ligand
      (sRANKL), and interleukin 6 (IL-6). Detection of CD55- and/or CD59-deficient red
      cell populations was performed after diagnosis. Patients with MM had elevated
      mean baseline NTX, TRACP-5b, sRANKL, and IL-6 levels compared with controls,
      whereas the mean values of bALP, OC, and OPG were significantly decreased. Four
      patients had no osteolytic lesions, whereas 8 patients had 1 to 3 lytic lesions,
      and 31 patients had more than 3 lytic lesions and/or pathologic fractures in the
      skeletal survey. CD55- and/or CD59-deficient red cell populations were observed
      in 56% of patients with MM. There was a strong correlation between the presence
      of PNH-like erythrocytes and increased bone resorption, as measured by NTX, TRACP
      5b, and sRANKL/OPG ratio (P < .03, P < .02, and P < .02, respectively). There was
      also a significant correlation between PNH phenotype and severe bone disease (P <
      .02). These results suggest that there is a possible link between PNH phenotype
      and increased osteoclastic activity in MM owing to a potential effect of myeloma
      microenvironment on a preexisting PNH clone. Further studies are required for
      clarifying this phenomenon and investigating possible mechanisms of this unusual
      association.

PMID- 14686494
TI  - Monitoring minimal residual disease in leukemia using real-time quantitative
      polymerase chain reaction for Wilms tumor gene (WT1).
AB  - We previously showed that Wilms tumor gene (WT1) expression level, measured by
      quantitative reverse transcriptase polymerase chain reaction (RT-PCR), was useful
      as an indicator of minimal residual disease (MRD) in leukemia and myelodysplastic
      syndrome. However, in conventional quantitative RT-PCR (CQ-PCR), RT-PCR must be
      performed for various numbers of cycles depending on WT1 expression level. In the
      present study, we developed a new real-time quantitative RT-PCR (RQ-PCR) method
      for quantitating WT1 transcripts. Results of intraassay and interassay
      variability tests demonstrated that the real-time WT1 assay had high
      reproducibility. WT1 expression levels measured by the RQ- and the CQ-PCR methods
      were strongly correlated (r = 0.998). Furthermore, a strong correlation was
      observed among WT1 transcript values normalized with 3 different control genes
      (beta-actin, ABL, and glyceraldehyde-3-phosphate dehydrogenase) and between
      relative WT1 transcript values with WT1 expression in K562 cells as the reference
      and absolute WT1 transcript copy numbers per microgram RNA. When WT1 expression
      and minor bcr-abl expression were concurrently monitored in 2 patients with bcr
      abl-positive acute lymphoblastic leukemia, both MRDs changed mostly in parallel,
      indicating the reliability and validity of our RQ-PCR method. In conclusion, this
      RQ-PCR method is convenient and reliable for monitoring MRD and enables routine
      clinical use of a WT1 assay.

PMID- 14686495
TI  - Detection of two cell populations corresponding to distinct maturation stages in
      API-2/MLT-positive mucosa-associated lymphoid tissue lymphoma cells proliferating
      in pleural effusion.
AB  - A 66-year-old man was admitted to our hospital because of an intra-abdominal
      tumor and pleural effusion (PE). Immunoelectrophoresis of the serum showed
      immunoglobulin M (IgM) kappa paraprotein (7330 mg/dL). Abnormal plasmacytoid
      cells were seen in both the peripheral blood (PB) and the bone marrow (BM).
      Computed tomography scans showed extensive thickening of the gastric wall and
      bilateral massive PE without lymph node or pulmonary involvement. A histologic
      examination of the gastric mucosa showed a diffuse infiltration of small- to
      medium-sized lymphoid CD20-bearing cells, some of which showed a plasmacytoid
      morphology. Lymphoepithelial lesions were demonstrated with an
      immunohistochemical stain. The diagnosis was gastric mucosa-associated lymphoid
      tissue (MALT) lymphoma infiltrating to the PE, PB, and BM. The PE contained
      numerous lymphoid cells with plasmacytoid morphology that Southern blotting
      analysis showed to have a monoclonal IgH gene rearrangement pattern. The cells
      seemed to be divided into two populations according to their surface markers:
      mature B-cells (CD19+CD20+CD22+CD21+CD38-) and secretory B-cells
      (CD19+CD20(dim)CD22-CD21-CD38+). The reverse transcriptase-polymerase chain
      reaction technique detected the API-2/MLT transcript in the PE and PB. The
      patient had a good response to fludarabine treatment, which was followed with
      rituximab therapy. In general, gastric MALT lymphoma cells have a tendency to
      differentiate into plasma cells. In this article, we show that the cell character
      of API-2/MLT-positive MALT lymphoma is preserved even when the cells are
      disseminated. This is the first published case, to our knowledge, in which two
      differentiation stages of MALT lymphoma cells infiltrating into PE have been
      confirmed by flow cytometric analysis.

PMID- 14686496
TI  - Recurrence of acute myelogenous leukemia with the same AML1/ETO breakpoint as at
      diagnosis after complete remission lasting 15 years: analysis of stored bone
      marrow smears.
AB  - The AML1/ETO fusion gene is expressed in virtually all patients with
      t(8;21)(q22;q22) acute myelogenous leukemia (AML). Long-term complete remission
      (CR) of AML with t(8;21) has been observed despite the presence of residual AML1/
      ETO fusion transcripts, although detection may depend on the sensitivity of the
      methods used. We examined a patient with recurrent AML who showed the
      t(8;21)(q22;q22) chromosomal abnormality following a CR of 15 years. The blast
      cells at the time of recurrence expressed the AML1/ETO fusion transcript, and the
      breakpoint of the AML1 gene was located on intron 5. Southern blot analysis of
      the DNA extracted from bone marrow slides that had been made and stored for 15
      years revealed the same rearrangement pattern of the AML1 gene. Furthermore, the
      junction sequences between the AML1 and the ETO genes, analyzed by long-distance
      inverse polymerase chain reaction, proved to be completely identical. These
      findings can be interpreted in two ways: (1) The initial leukemia clone persisted
      and finally relapsed after 15 years in the dormant state. (2) AML developed in
      different subclones having the same AML1/ETO junctional sequences but with
      additional genetic changes (second hit).

PMID- 14686497
TI  - Chronic graft-versus-host disease following varicella-zoster virus infection in
      allogeneic stem cell transplant recipients.
AB  - We describe 2 allogeneic stem cell transplantation patients who developed chronic
      graft-versus-host disease (GVHD) after dermatomal varicella-zoster virus (VZV)
      infection. Localized zoster did not respond to oral valaciclovir but did resolve
      with intravenous aciclovir. However, skin eruptions, eye/oral dryness, and liver
      dysfunction were observed at the healing stage of localized zoster, suggesting
      development of GVHD. Intensification of immunosuppressive therapy was required to
      control GVHD. Quantitative real-time PCR for VZV DNA was used to distinguish
      liver involvement by chronic GVHD from visceral dissemination of VZV in 1
      patient. VZV infection may trigger chronic GVHD after allogeneic stem cell
      transplantation.

PMID- 14686498
TI  - Prevalence and clinical significance of hepatitis C virus infection in Thai
      patients with thalassemia.
AB  - Hepatitis C virus (HCV) infection is a common cause of liver disease in
      thalassemia major patients in Western, especially Mediterranean, countries. Its
      significance in thalassemic patients from Southeast Asia has not been critically
      evaluated. In this report, we describe our study of the prevalence of HCV
      infection among Thai patients with thalassemia. The relationships of the
      infection to blood transfusion and the infection's effects on liver function have
      also been determined. Of the 104 patients studied, 21 (20.2%) tested positively
      by enzyme immunoassay for anti-HCV antibody, whereas only 2 patients (2%) had the
      hepatitis B surface antigen. There was no significant relationship between the
      presence of anti-HCV antibodies and the number and frequency of blood
      transfusions. In fact, 2 patients (10%) who tested positive for anti-HCV
      antibodies had never received transfusions. Patients with anti-HCV antibodies had
      significantly abnormal liver functions, such as higher levels of serum aspartate
      aminotransferase (SGOT) and alanine aminotransferase (SGPT) and lower levels of
      serum albumin, compared with patients without anti-HCV antibodies (P = .021,
      .017, and .004, respectively). However, there were also significant correlations
      between iron status as indicated by transferrin saturation or serum ferritin
      levels and SGOT, SGPT, and gamma-glutamyltransferase (GGT) levels. Moreover,
      abnormal liver function as represented by elevated levels of SGOT, SGPT, GGT, and
      serum alkaline phosphatase was observed more frequently in patients with iron
      overload than in patients with a lower degree of iron burden. The presence of HCV
      did not alter the effects of iron overload on liver function. The findings
      suggest that both HCV and iron overload are the main causes of abnormal liver
      function in Thai patients with thalassemia. The treatment of both problems, if
      coexisting in patients with thalassemia, is required to prevent progression to
      chronic liver disease.

PMID- 14686499
TI  - An ideal observer with channels versus feature-independent processing of spatial
      frequency and orientation in visual search performance.
AB  - An influential assumption for the front end of models in vision, visual search,
      and object recognition is an analysis of independent features that correspond to
      basic image properties, such as motion, shape, and color. Empirically, one common
      test of independent features (a cue-summation study) measures performance with
      increasing available cues or features, with improving performance leading to
      conclusions of summation across independent features. In a study by Shimozaki et
      al. [J. Vision 2, 354-370 (2002)], both ideal and human observers showed no
      summation with large stimulus differences, in contrast to independent-feature
      models and suggesting that stimulus information (as assessed by an ideal
      observer) might affect cue-summation studies. Extending the previous summation
      study, observers performed a visual search of four Gabors differing in only
      orientation, only spatial frequency, or both orientation and spatial frequency,
      across a range of target-distractor differences. An ideal observer underpredicted
      human summation for small differences, whereas the independent-orientation and
      spatial-frequency feature models overpredicted human summation for large
      differences. An ideal observer with channels jointly tuned to spatial frequency
      and orientation predicted human performance across both small and large target
      distractor differences.

PMID- 14686500
TI  - Time course of adaptation to stimuli presented along cardinal lines in color
      space.
AB  - Visual sensitivity is a process that allows the visual system to maintain optimal
      response over a wide range of ambient light levels and chromaticities. Several
      studies have used variants of the probe-flash paradigm to show that the time
      course of adaptation to abrupt changes in ambient luminance depends on both
      receptoral and postreceptoral mechanisms. Though a few studies have explored how
      these processes govern adaptation to color changes, most of this effort has
      targeted the L-M-cone pathway. The purpose of our work was to use the probe-flash
      paradigm to more fully explore light adaptation in both the L-M- and the S-cone
      pathways. We measured sensitivity to chromatic probes presented after the onset
      of a 2-s chromatic flash. Test and flash stimuli were spatially coextensive 2
      degrees fields presented in Maxwellian view. Flash stimuli were presented as
      excursions from white and could extended in one of two directions along an
      equiluminant L-M-cone or S-cone line. Probes were presented as excursions from
      the adapting flash chromaticity and could extend either toward the spectrum locus
      or toward white. For both color lines, the data show a fast and slow adaptation
      component, although this was less evident in the S-cone data. The fast and slow
      components were modeled as first- and second-site adaptive processes,
      respectively. We find that the time course of adaptation is different for the two
      cardinal pathways. In addition, the time course for S-cone stimulation is
      polarity dependent. Our results characterize the rapid time course of adaptation
      in the chromatic pathways and reveal that the mechanics of adaptation within the
      S-cone pathway are distinct from those in the L-M-cone pathways.

PMID- 14686501
TI  - Dynamic accommodation response in the presence of astigmatism.
AB  - It has been suggested that in the presence of astigmatism some individuals make
      cyclic changes in focus over the astigmatic interval to obtain better visual
      performance. The aim in the present study was to identify such cyclic
      accommodative behavior and to characterize the variability of the response in the
      presence of astigmatism. The dynamic accommodation response in the presence of
      induced astigmatism was recorded objectively with an infrared optometer in seven
      young adults. Astigmatism led directly to increased accommodative variability in
      certain individuals. In two of seven participants there was evidence for
      aperiodic cyclic accommodative responses between different portions of the
      astigmatic interval. However, the amplitude of these tracking responses was much
      smaller than the astigmatic interval.

PMID- 14686502
TI  - Measuring eye aberrations with Hartmann-Shack wave-front sensors: should the
      irradiance distribution across the eye pupil be taken into account?
AB  - A usual approximation in Hartmann-Shack aberrometry is that the centroid
      displacements are proportional to the spatial averages of the wave-front slopes
      at the sampling subapertures. However, these spatial averages are actually
      weighted by the local irradiance distribution across each microlens. The
      irradiance across the eye pupil is not uniform in usual reflectometric
      aberrometers, which is due to several factors including retinal scattering and
      cone waveguiding directionality. It is shown that neglecting this fact in usual
      least-squares reconstruction procedures gives rise to a biased estimation of the
      aberration coefficients. The magnitude of this bias depends on the actual
      irradiance distribution across the eye pupil, the mode being estimated, the
      detailed modal composition of the aberrated wave front, and the geometry of the
      wave-front sampling array. Order-of-magnitude calculations suggest that this bias
      may well be in the range 5%-10% for relatively smooth irradiance distributions.
      The systematic nature of this error makes it advisable to check for its presence
      and, if required, to compensate for it by an adequate choice of the least-squares
      reconstruction matrix.

PMID- 14686503
TI  - Three-dimensional spatial grouping affects estimates of the illuminant.
AB  - The brightnesses (i.e., perceived luminance) of surfaces within a three
      dimensional scene are contingent on both the luminances and the spatial
      arrangement of the surfaces. Observers viewed a CRT through a haploscope that
      presented simulated achromatic surfaces in three dimensions. They set a test
      patch to be approximately 33% more intense than a comparison patch to match the
      comparison patch in brightness, which is consistent with viewing a real scene
      with a simple lightning interpretation from which to estimate a different level
      of illumination in each depth plane. Randomly positioning each surface in either
      depth plane minimized any simple lighting interpretation, concomitantly reducing
      brightness differences to approximately 8.5%, although the immediate surrounds of
      the test and comparison patches continued to differ by a 5:1 luminance ratio.

PMID- 14686504
TI  - Optimizing the near field around silver tips.
AB  - Owing to their promise of obtaining optical as well as topographic information in
      nanometer scale, apertureless near-field scanning optical microscopy (NSOM) and
      apertureless near-field scanning optical spectroscopy have drawn much attention
      recently. However, NSOM is still not a mature technique. A proper understanding
      of and the ability to tune the near field around the tip end is critically
      important in NSOM instrumentation and in NSOM image interpretation. On the basis
      of reflection geometry, we systematically studied the effects of a number of
      parameters pertinent in the application of apertureless NSOM, e.g., polarization,
      incident angle, wavelength of the incident laser, tip material, and tip length,
      by using the generalized field propagator technique. Our results show that all
      the above parameters have a significant influence on near-field enhancement and
      that care must be taken in the design of the experiment in order to maximize the
      near field. In addition to apertureless NSOM and spectroscopy, apertureless near
      field lithography can benefit from these simulation results.

PMID- 14686505
TI  - Computational imaging with the logarithmic asphere: theory.
AB  - A theory for an integrated system is described that combines a logarithmic
      aspheric imaging lens with maximum-entropy digital processing to extend the depth
      of field ten times over that of a conventional lens and to provide near
      diffraction-limited resolution. Two types of logarithmic aspheres are derived
      that are circularly symmetric lenses with controlled continuous radial variation
      of focal length. The details of an iterative maximum-entropy algorithm are also
      presented. The properties of convergence and speed of the algorithm are greatly
      improved by introducing a metric parameter to adjust the weight of different
      pixel values of the recovered picture in each loop properly.

PMID- 14686506
TI  - Electromagnetic beam diffraction by a finite lamellar structure: an aperiodic
      coupled-wave method.
AB  - We have developed a new formulation of the coupled-wave method (CWM) to handle
      aperiodic lamellar structures, and it will be referred to as the aperiodic
      coupled-wave method (ACWM). The space is still divided into three regions, but
      the fields are written by use of their Fourier integrals instead of the Fourier
      series. In the modulated region the relative permittivity is represented by its
      Fourier transform, and then a set of integro-differential equations is derived.
      Discretizing the last system leads to a set of ordinary differential equations
      that is reduced to an eigenvalue problem, as is usually done in the CWM. To
      assess the method, we compare our results with three independent formalisms: the
      Rayleigh perturbation method for small samples, the volume integral method, and
      the finite-element method.

PMID- 14686507
TI  - Extended Nijboer-Zernike representation of the vector field in the focal region
      of an aberrated high-aperture optical system.
AB  - Taking the classical Ignatowsky/Richards and Wolf formulas as our starting point,
      we present expressions for the electric field components in the focal region in
      the case of a high-numerical-aperture optical system. The transmission function,
      the aberrations, and the spatially varying state of polarization of the wave
      exiting the optical system are represented in terms of a Zernike polynomial
      expansion over the exit pupil of the system; a set of generally complex
      coefficients is needed for a full description of the field in the exit pupil. The
      field components in the focal region are obtained by means of the evaluation of a
      set of basic integrals that all allow an analytic treatment; the expressions for
      the field components show an explicit dependence on the complex coefficients that
      characterize the optical system. The electric energy density and the power flow
      in the aberrated three-dimensional distribution in the focal region are obtained
      with the expressions for the electric and magnetic field components. Some
      examples of aberrated focal distributions are presented, and some basic
      characteristics are discussed.

PMID- 14686508
TI  - Integrated color pixels in 0.18-microm complementary metal oxide semiconductor
      technology.
AB  - Following the trend of increased integration in complementary metal oxide
      semiconductor (CMOS) image sensors, we have explored the potential of
      implementing light filters by using patterned metal layers placed on top of each
      pixel's photodetector. To demonstrate wavelength selectivity, we designed and
      prototyped integrated color pixels in a standard 0.18-microm CMOS technology.
      Transmittance of several one-dimensional (1D) and two-dimensional (2D) patterned
      metal layers was measured under various illumination conditions and found to
      exhibit wavelength selectivity in the visible range. We performed (a) wave optics
      simulations to predict the spectral responsivity of an uncovered reference pixel
      and (b) numerical electromagnetic simulations with a 2D finite-difference time
      domain method to predict transmittances through 1D patterned metal layers. We
      found good agreement in both cases. Finally, we used simulations to predict the
      transmittance for more elaborate designs.

PMID- 14686509
TI  - General solution of the coupled-wave equations of acousto-optics.
AB  - The basic problem of the diffraction of an optical plane wave by an acoustic
      plane wave in an anisotropic homogeneous medium is considered. The acousto
      optical interaction is considered indifferently of the isotropic or of the
      birefringent type. Coupled-wave equations are obtained rigorously and cast into
      an eigenvalue value problem. A general solution is obtained for the diffraction
      efficiency of diffracted orders, for any interaction length and diffraction
      regime. The theory includes the Bragg regime, the Raman-Nath regime, and all
      intermediate situations in the same formulation. The method of solution is both
      exact and computationally efficient. It is similar in character to the rigorous
      coupled-wave analysis of Moharam and Gaylord but differs by the choice of basis
      functions adapted to propagating rather than static gratings. Examples are given
      for acousto-optical interaction in paratellurite, TeO2.

PMID- 14686510
TI  - Influence of spatial coherence on scattering by a particle.
AB  - We analyze the effect of partial spatial coherence on the scattering of light by
      an arbitrary particle. We extend the definition of the extinction cross section
      to spatially partially coherent fields. We then discuss the effect of the partial
      coherence on the extinction scattering cross section by introducing the Wigner
      transform. It is shown that for rotationally invariant scatterers, the extinction
      cross section does not depend on the coherence of the incident field. The effect
      of partial coherence on the angular behavior of the scattered intensity is also
      discussed in the framework of the Wigner transform. The implications for
      practical applications are considered.

PMID- 14686511
TI  - Comparison of the auxiliary function method and the discrete-ordinate method for
      solving the radiative transfer equation for light scattering.
AB  - Two methods for solving the radiative transfer equation are compared with the aim
      of computing the angular distribution of the light scattered by a heterogeneous
      scattering medium composed of a single flat layer or a multilayer. The first
      method [auxiliary function method (AFM)], recently developed, uses an auxiliary
      function and leads to an exact solution; the second [discrete-ordinate method
      (DOM)] is based on the channel concept and needs an angular discretization. The
      comparison is applied to two different media presenting two typical and extreme
      scattering behaviors: Rayleigh and Mie scattering with smooth or very anisotropic
      phase functions, respectively. A very good agreement between the predictions of
      the two methods is observed in both cases. The larger the number of channels used
      in the DOM, the better the agreement. The principal advantages and limitations of
      each method are also listed.

PMID- 14686512
TI  - Fourth- and higher-order small-perturbation solution for scattering from
      dielectric rough surfaces.
AB  - A recursive solution of the small-perturbation method for rough surface
      scattering is presented. These results permit fourth- and higher-order
      corrections to rough surface scattering coefficients to be determined in a form
      that explicitly separates surface and electromagnetic properties. Sample results
      are presented for the fourth-order correction to the specular reflection
      coefficient of a rough surface and the sixth-order correction to incoherent
      scattering cross sections.

PMID- 14686513
TI  - Enhanced specular peaks in diffuse light scattering from weakly rough metal
      surfaces.
AB  - We employ Monte Carlo techniques based on the reduced Rayleigh equations to study
      an enhanced specular peak that appears in the light scattered from weakly rough
      metal surfaces. This peak is not associated with the specular reflection but
      instead appears, with finite angular width, at the specular angle of the mean
      diffusely scattered intensity. As is the case with backscattering enhancement,
      the specular peak arises from the interference of contributions of multiple
      scattering processes related to surface plasmon polariton excitation. We
      demonstrate that the specular peak is seen clearly for surface roughness that has
      a conventional Gaussian power spectrum. Further, we show that the peak appears
      more distinctly for roughness whose power spectrum has a new rectangular form,
      which is proposed here with the intent of better isolation of the scattering
      processes essential to the specular peak. Finally, for a pair of rough surfaces
      that have appropriately correlated surface roughness, it is found that the cross
      correlation of scattered amplitudes presents a well-isolated specular peak, which
      directly demonstrates the constructive interference that produces the effect.

PMID- 14686514
TI  - In vivo demonstration of the ultrasound-modulated light technique.
AB  - We present, to our knowledge for the first time, results of ultrasound-modulated
      light signals on living tissues. In particular, we analyze, both theoretically
      and experimentally, the effect of speckle fluctuations on the signal. We find
      that two different kinds of noise compete--shot noise and speckle noise--and are
      present at different levels in static phantoms and ex vivo tissue samples on the
      one hand and in dynamic phantoms and living tissues on the other hand.

PMID- 14686515
TI  - Generalized diffusion model in optical tomography with clear layers.
AB  - We introduce a generalized diffusion equation that models the propagation of
      photons in highly scattering domains with thin nonscattering clear layers.
      Classical diffusion models break down in the presence of clear layers. The model
      that we propose accurately accounts for the clear-layer effects and has a
      computational cost comparable to that of classical diffusion. It is based on
      modeling the propagation in the clear layer as a local tangential diffusion
      process. It can be justified mathematically in the limit of small mean free paths
      and is shown numerically to be very accurate in two- and three-dimensional
      idealized cases. We believe that this model can be used as an accurate forward
      model in optical tomography.

PMID- 14686516
TI  - Differential relations for the imaging coefficients of asymmetric systems.
AB  - We consider imaging properties embedded in the point eikonal for first-order
      asymmetric optical systems. We provide geometrical interpretations for the
      coefficients of the eikonal functions and proceed to show that there exist
      differential relations between them. The differentials are computed with respect
      to the position of the reference planes in the object or image spaces.

PMID- 14686517
TI  - Underwater binocular imaging of aerial objects versus the position of eyes
      relative to the flat water surface.
AB  - The apparent position, size, and shape of aerial objects viewed binocularly from
      water change as a result of the refraction of light at the water surface. Earlier
      studies of the refraction-distorted structure of the aerial binocular visual
      field of underwater observers were restricted to either vertically or
      horizontally oriented eyes. Here we calculate the position of the binocular image
      point of an aerial object point viewed by two arbitrarily positioned underwater
      eyes when the water surface is flat. Assuming that binocular image fusion is
      performed by appropriate vergent eye movements to bring the object's image onto
      the foveae, the structure of the aerial binocular visual field is computed and
      visualized as a function of the relative positions of the eyes. We also analyze
      two erroneous representations of the underwater imaging of aerial objects that
      have occurred in the literature. It is demonstrated that the structure of the
      aerial binocular visual field of underwater observers distorted by refraction is
      more complex than has been thought previously.

PMID- 14686518
TI  - Role of evanescent waves in power calculations for counterpropagating beams.
AB  - A general expression is obtained for the time-average power passing through a
      plane transverse to the direction of propagation for two counterpropagating
      electromagnetic beams. Each beam is represented by its plane-wave spectrum, which
      contains both propagating and evanescent plane waves. The expression clearly
      shows that, under certain conditions, the evanescent plane waves contribute to
      the time-average power passing through the plane. This is in contrast to the case
      of a single electromagnetic beam, in which only the propagating plane waves
      contribute to the time-average power passing through the plane. The utility of
      the expression is demonstrated with a practical example: a line current placed
      over a dielectric slab. Here the counterpropagating beams are the incident and
      reflected fields in the region between the current and the slab. The expression
      is applied to a plane in this region, and it is used to determine the time
      average power associated with the evanescent waves passing through this plane.
      This power is then shown to be equal to the time-average power carried by the
      guided modes of the slab.

PMID- 14686519
TI  - Evanescent and propagating fields of a strongly focused beam.
AB  - Evanescent- and propagating-field distributions from a strongly-focused-wave beam
      with subwavelength waist w(a) << lambda as a function of polar angle and distance
      are investigated. Exact amplitudes and intensities of evanescent E(ev) and
      propagating E(p) fields, including interference terms, are presented both in near
      and far-field regions. It is shown that the amplitude of E(ev) decays as exp(
      r/w(a)) in the near-field region and that evanescent waves do not contribute to
      the far field in the forward direction as they do in the transverse directions
      theta = pi/2, even though the oscillating evanescent field of the same strength
      but opposite in sign to the propagating field exists in the transverse plane.

PMID- 14686520
TI  - Sampling expansions for three-dimensional light amplitude distribution in the
      vicinity of an axial image point: comment.
AB  - Landgrave and Berriel-Valdos presented axial and radial sampling expansions for
      three-dimensional light amplitude distribution around the Gaussian focal point.
      [J. Opt. Soc. Am. A 14, 2962 (1997)]. The expansions were obtained under the
      assumption that the pupil function was rotationally symmetric. We present a new
      derivation of the axial expansion that does not make use of arbitrary formal
      assumptions used by Landgrave and Berriel-Valdos and eliminates some faults of
      the derivation given by Arsenault and Boivin, who published this expansion in
      1967 [J. Appl. Phys. 38, 3988 (1967)]. We also discuss generalizations of the
      axial expansion to the case of pupils that exhibit no symmetry with respect to
      the axis considered.

PMID- 14686521
TI  - Sexual dimorphism and adaptive speciation: two sides of the same ecological coin.
AB  - Models of adaptive speciation are typically concerned with demonstrating that it
      is possible for ecologically driven disruptive selection to lead to the evolution
      of assortative mating and hence speciation. However, disruptive selection could
      also lead to other forms of evolutionary diversification, including ecological
      sexual dimorphisms. Using a model of frequency-dependent intraspecific
      competition, we show analytically that adaptive speciation and dimorphism require
      identical ecological conditions. Numerical simulations of individual-based models
      show that a single ecological model can produce either evolutionary outcome,
      depending on the genetic independence of male and female traits and the potential
      strength of assortative mating. Speciation is inhibited when the genetic basis of
      male and female ecological traits allows the sexes to diverge substantially. This
      is because sexual dimorphism, which can evolve quickly, can eliminate the
      frequency-dependent disruptive selection that would have provided the impetus for
      speciation. Conversely, populations with strong assortative mating based on
      ecological traits are less likely to evolve a sexual dimorphism because females
      cannot simultaneously prefer males more similar to themselves while still
      allowing the males to diverge. This conflict between speciation and dimorphism
      can be circumvented in two ways. First, we find a novel form of speciation via
      negative assortative mating, leading to two dimorphic daughter species. Second,
      if assortative mating is based on a neutral marker trait, trophic dimorphism and
      speciation by positive assortative mating can occur simultaneously. We conclude
      that while adaptive speciation and ecological sexual dimorphism may occur
      simultaneously, allowing for sexual dimorphism restricts the likelihood of
      adaptive speciation. Thus, it is important to recognize that disruptive selection
      due to frequency-dependent interactions can lead to more than one form of
      adaptive splitting.

PMID- 14686522
TI  - The evolution of static allometry in sexually selected traits.
AB  - Although it has been the subject of verbal theory since Darwin, the evolution of
      morphological trait allometries remains poorly understood, especially in the
      context of sexual selection. Here we present an allocation trade-off model that
      predicts the optimal pattern of allometry under different selective regimes. We
      derive a general solution that has a simple and intuitive interpretation and use
      it to investigate several examples of fitness functions. Verbal arguments have
      suggested cost or benefit scenarios under which sexual selection on signal or
      weapon traits may favor larger individuals with disproportionately larger traits
      (i.e., positive allometry). However, our results suggest that this is necessarily
      true only under a precisely specified set of conditions: positive allometry will
      evolve when the marginal fitness gains from an increase in relative trait size
      are greater for large individuals than for small ones. Thus, the optimal
      allometric pattern depends on the precise nature of net selection, and simple
      examples readily yield isometry, positive or negative allometry, or polymorphisms
      corresponding to sigmoidal scaling. The variety of allometric patterns predicted
      by our model is consistent with the diversity of patterns observed in empirical
      studies on the allometries of sexually selected traits. More generally, our
      findings highlight the difficulty of inferring complex underlying processes from
      simple emergent patterns.

PMID- 14686523
TI  - Morphometric heterochrony and the evolution of growth.
AB  - Heterochrony has been an influential perspective on the evolution of
      morphologies, a circumstance mostly due to a strategic shift of the theory to the
      analysis of growth and measurable traits. A difficulty in testing hypotheses of
      heterochrony in the morphometric realm, and therefore in establishing its
      evolutionary relevance, has been the absence of an explicit criterion of homology
      in comparisons supposed to reveal paedomorphosis and peramorphosis. Based on the
      formalism of ontogenetic and allometric trajectories, we defined a criterion of
      primary homology in the context of morphometric characters that requires only a
      comparison between metric traits from ontogenetic series of two or more taxa. On
      the one hand, such a criterion allows for the calculation of values of shape
      slopes and allometric coefficients in descendants supposedly affected by changes
      in ontogenetic timing, thereby supplying an analytical tool for testing
      hypotheses of heterochrony. On the other hand, the concept of morphometric
      homology establishes the descriptive limits of paedomorphosis and peramorphosis,
      showing, for example, that the model of sequential hypermorphosis applied to the
      evolution of human encephalization is not within the descriptive scope of the
      morphological markers of heterochrony. Sequential hypermorphosis is a successful
      model of morphometric evolution, as further illustrated by the match between our
      mathematical deductions and the empirical results obtained by analyses of brain
      growth data. By exploring the properties of multiphasic polynomial functions, we
      deduce equations that define the relationship between developmental delay or
      acceleration and their effect on adult brain size. Together with the primary
      criterion of homology, we demonstrate that sequential hypermorphosis could
      generate the large modern human brain, but such brain is neither paedomorphic nor
      peramorphic. Our approach based on homology and allometry indicates that the
      evolution of growth is richer in phenomena than heterochrony can account for, and
      accordingly we argue that morphometric theory can expand its descriptive and
      heuristic scope by looking beyond the limits imposed by paedomorphosis and
      peramorphosis.

PMID- 14686524
TI  - Testing for equal rates of cladogenesis in diverse taxa.
AB  - Taxa differ widely in numbers of species, which may be due either to chance alone
      or to factors that cause differences in speciation and extinction rates between
      taxa. To test whether an observed distribution of species over taxa differs from
      the distribution expected from chance alone, one must take into account that
      neither speciation nor extinction rates are known. This paper introduces a way to
      estimate speciation and extinction probabilities from the distribution of extant
      species over families and to test whether the observed distribution is different
      from expected. Application of this procedure to the distributions of bird,
      hexapod, primate, and angiosperm species over taxa provides statistical evidence
      of differences in rates of cladogenesis between taxa.

PMID- 14686525
TI  - Cryptic repeated genomic recombination during speciation in Gossypium
      gossypioides.
AB  - The Mexican cotton Gossypium gossypioides is a perplexing entity, with
      conflicting morphological, cytogenetic, and molecular evidence of its
      phylogenetic affinity to other American cottons. We reevaluated the evolutionary
      history of this enigmatic species using 16.4 kb of DNA sequence. Phylogenetic
      analyses show that chloroplast DNA (7.3 kb), nuclear ribosomal internal
      transcribed spacers (ITS; 0.69 kb), and unique nuclear genes (8.4 kb) yield
      conflicting resolutions for G. gossypioides. Eight low-copy nuclear genes provide
      a nearly unanimous resolution of G. gossypioides as the basalmost American
      diploid cotton, whereas cpDNA sequences resolve G. gossypioides deeply nested
      within the American diploid clade sister to Peruvian G. raimondii, and ITS places
      G. gossypioides in an African (rather than an American) clade. These data, in
      conjunction with previous evidence from the repetitive fraction of the genome,
      implicate a complex history for G. gossypioides possibly involving temporally
      separated introgression events from genetically divergent cottons that are
      presently restricted to different hemispheres. Based on repetitive nuclear DNA,
      it appears that G. gossypioides experienced nuclear introgression from an African
      species shortly after divergence from the remainder of the American assemblage.
      More recently, hybridization with a Mexican species may have resulted in cpDNA
      introgression, and possibly a second round of cryptic nuclear introgression.
      Gossypium gossypioides provides a striking example of the previously unsuspected
      chimeric nature of some plant genomes and the resulting phylogenetic complexity
      produced by multiple historical reticulation events.

PMID- 14686526
TI  - Patterns of nucleotide diversity in two species of Mimulus are affected by mating
      system and asymmetric introgression.
AB  - The evolutionary transition from outcrossing to self-fertilization has far
      reaching implications for patterns of intraspecific genetic diversity and the
      potential for speciation. Using DNA sequence variation at two nuclear loci, we
      examined the divergence history of two closely related species of Mimulus. To
      investigate the effects of mating system and introgressive hybridization on the
      outcrossing M. guttatus and the selfing M. nasutus, we inspected nucleotide
      diversity within and between natural populations spanning the species' geographic
      ranges. High sequence similarity among populations of the selfing M. nasutus
      points to a single evolutionary origin for the species. Consistent with their
      distinct mating systems, all genetic variation in M. nasutus is distributed among
      populations, whereas M. guttatus exhibits appreciable levels of nucleotide
      diversity within populations. Silent genetic diversity is extensive in M.
      guttatus (mean theta(sil)/site = 0.077) and greatly exceeds the predicted twofold
      elevation in neutral variation for outcrossers relative to selfers. The finding
      of several M. guttatus sequences that share complete identity with sequences from
      M. nasutus suggests that recent asymmetric introgression may have occurred. We
      argue that exceptionally high nucleotide diversity in M. guttatus is consistent
      with a long-term history of directional introgression from M. nasutus to M.
      guttatus throughout the divergence of these two species.

PMID- 14686527
TI  - The diversification of Halenia (Gentianaceae): ecological opportunity versus key
      innovation.
AB  - The plant genus Halenia (Gentianaceae) consists of herbs growing in temperate and
      tropical alpine habitats and most species possess flowers in which nectar is
      produced in spurs. This probably helps reward only specialized long-tongued
      pollinators, and a narrow pollinator/flower relationship is thought to accelerate
      diversification rates (a key innovation). To test the pattern of diversification
      of Halenia against the unspurred sister group we reconstructed phylogenetic
      relationships among 22 species plus outgroups using nuclear ITS and chloroplast
      rpl16 intron sequence data. We show that Halenia originated in East Asia and
      migrated via North America into Central America. From there, it colonized South
      America three times independently, probably within the last million years.
      Significant changes in diversification rates were found during the evolution of
      Halenia using a sister group method, a likelihood method, and a diversity-through
      time plot. In contrast to other studies, we could not observe a direct speciation
      rate effect of the evolution of nectar spurs in comparison with the unspurred
      sister group of Halenia. Rather, increases in diversification occurred following
      the colonization of Central and South America by spurred progenitor taxa. This
      later switch in diversification may have resulted from the availability of new
      geographical and ecological opportunities, or from the availability of more and
      different pollinators in these regions. Following the latter hypothesis, the
      nectar spurs were a preadaption and functioned as a key innovation only in this
      new biotic environment. After an initial rapid increase, a reduction in
      diversification rate was observed in Central America, probably illustrating
      density dependence of speciation rates. Finally, we found preliminary evidence
      for the key innovation hypothesis in geologically young spurred and unspurred
      lineages of Halenia in South America.

PMID- 14686528
TI  - Fitness costs of chemical defense in Plantago lanceolata L.: effects of nutrient
      and competition stress.
AB  - Fitness costs of defense are often invoked to explain the maintenance of genetic
      variation in levels of chemical defense compounds in natural plant populations.
      We investigated fitness costs of iridoid glycosides (IGs), terpenoid compounds
      that strongly deter generalist insect herbivores, in ribwort plantain (Plantago
      lanceolata L.) using lines that had been artificially selected for high and low
      leaf IG concentrations for four generations. Twelve maternal half-sib families
      from each selection line were grown in four environments, consisting of two
      nutrient and two competition treatments. We tested whether: (1) in the absence of
      herbivores and pathogens, plants from lines selected for high IG levels have a
      lower fitness than plants selected for low IG levels; and (2) costs of chemical
      defense increase with environmental stress. Vegetative biomass did not differ
      between selection lines, but plants selected for high IG levels produced fewer
      inflorescences and had a significantly lower reproductive dry weight than plants
      selected for low IG levels, indicating a fitness cost of IG production. Line-by
      nutrient and line-by-competition interactions were not significant for any of the
      fitness-related traits. Hence, there was no evidence that fitness costs increased
      with environmental stress. Two factors may have contributed to the absence of
      higher costs under environmental stress. First, IGs are carbon-based chemicals.
      Under nutrient limitation, the relative carbon excess may result in the
      production of IGs without imposing a further constraint on growth and
      reproduction. Second, correlated responses to selection on IG levels indicate the
      existence of a positive genetic association between IG level and cotyledon size.
      At low nutrient level, a path analysis based on family means revealed that in the
      presence of competitors, the negative direct effect of a high IG level on
      aboveground plant dry weight was partly offset by a positive direct effect of the
      associated larger cotyledon size. This indicates that fitness costs of defense
      may be modulated by environment-specific fitness effects of genetically
      associated traits.

PMID- 14686529
TI  - Genetic architecture of a selection response in Arabidopsis thaliana.
AB  - Quantitative trait locus (QTL) mapping has become an established and effective
      method for studying the genetic architecture of complex traits. In this report,
      we use a QTL mapping approach in combination with data from a large selection
      experiment in Arabidopsis thaliana to explore a response to selection of
      experimental populations with differentiated genetic backgrounds. Experimental
      populations with genetic backgrounds derived from ecotypes Landsberg and
      Niederzenz were exposed to multiple generations of fertility and viability
      selection. This selection resulted in phenotypic shifts in a number of life
      history and fitness-related characters including early development time,
      flowering time, dry biomass, longevity, and fruit production. Quantitative trait
      loci were mapped for these traits and their positions were compared to previously
      characterized allele frequency changes in the experimental populations (Ungerer
      et al. 2003). Quantitative trait locus positions largely colocalized with genomic
      regions under strong and consistent selection in populations with differentiated
      genetic backgrounds, suggesting that alleles for these traits were selected
      similarly in differentiated genetic backgrounds. However, one QTL region
      exhibited a more variable response; being positively selected on one genetic
      background but apparently neutral in another. This study demonstrates how QTL
      mapping approaches can be combined with map-based population genetic data to
      study how selection acts on standing genetic variation in populations.

PMID- 14686530
TI  - Radiation, diversity, and host-plant interactions among island and continental
      legume-feeding psyllids.
AB  - Island archipelagos and insect-plant associations have both independently
      provided many useful systems for evolutionary study. The arytainine psyllid
      (Sternorrhyncha: Hemiptera) radiation on broom (Fabaceae: Genisteae) in the
      Canary Island archipelago provides a discrete system for examining the speciation
      of highly host-specific phytophagous insects in an island context. Phylogenetic
      reconstructions based on three datasets (adult and nymph morphological
      characters, and two mitochondrial DNA regions: part of the small subunit rRNA,
      and part of cytochrome oxidase I, cytochrome oxidase II and the intervening tRNA
      leucine) are generally consistent. The combined molecular tree provides a well
      supported estimate of psyllid relationships and shows that there have been
      several colonizations of the Macaronesian islands but that only one has resulted
      in a significant radiation. Psyllid diversification has apparently been
      constrained by the presence of suitable host groups within the genistoid legumes,
      and the diversity, distribution, and abundance of those groups. The phylogeny, by
      indicating pairs of sister species, allows putative mechanisms of speciation to
      be assessed. The most common conditions associated with psyllid speciation are
      geographical allopatry with a host switch to closely related hosts (six
      examples), or geographical allopatry on the same host (four examples). Where
      allopatric speciation involves a host switch, these have all been to related
      hosts. There is some evidence that switches between unrelated host plants may be
      more likely in sympatry. Only one sister pair (Aryrtainilla cytisi and A.
      telonicola) and the putative host races of Arytinnis modica are sympatric but on
      unrelated hosts, which may be a necessary condition for sympatric speciation in
      these insects. Where several psyllids share the same host, resources appear to be
      partitioned by ecological specialization and differing psyllid phenology.

PMID- 14686531
TI  - Divergent environments and population bottlenecks fail to generate premating
      isolation in Drosophila pseudoobscura.
AB  - While the feasibility of bottleneck-induced speciation is in doubt, population
      bottlenecks may still affect the speciation process by interacting with divergent
      selection. To explore this possibility, I conducted a laboratory speciation
      experiment using Drosophila pseudoobscura involving 78 replicate populations
      assigned in a two-way factorial design to both bottleneck (present vs. absent)
      and environment (ancestral vs. novel) treatments. Populations independently
      evolved under these treatments and were then tested for assortative mating and
      male mating success against their common ancestor. Bottlenecks alone did not
      generate any premating isolation, despite an experimental design that was
      conducive to bottleneck-induced speciation. Premating isolation also did not
      evolve in the novel environment treatment, neither in the presence nor absence of
      bottlenecks. However, male mating success was significantly reduced in the novel
      environment treatment, both as a plastic response to this environment and as a
      result of environment-dependent inbreeding effects in the bottlenecked
      populations. Reduced mating success of derived males will hamper speciation by
      enhancing the mating success of immigrant, ancestral males. Novel environments
      are generally thought to promote ecological speciation by generating divergent
      natural selection. In the current experiment, however, the novel environment did
      not cause the evolution of any premating isolation and it reduced the likelihood
      of speciation through its effects on male mating success.

PMID- 14686532
TI  - Recent radiation of endemic Caribbean Drosophila of the dunni subgroup inferred
      from multilocus DNA sequence variation.
AB  - Studies of island endemism provide a unique opportunity to elucidate fundamental
      mechanisms of speciation. Here we examine intra- and interspecific DNA sequence
      variation at four unlinked genetic loci among populations of the Drosophila dunni
      subgroup to provide a detailed genealogical portrait of the process of speciation
      among these island endemic species. Our data indicate two major rounds of
      diversification that have shaped the D. dunni subgroup. The first occurred 1.6
      2.6 million years ago and separated three major lineages, one in Puerto Rico and
      the Virgin Islands, a second in the northern Lesser Antilles and Barbados, and a
      third in St. Vincent and Grenada. A second round of diversification occurred in
      the last 96,000 years in the northern Lesser Antilles and Barbados. The four
      distinct species that resulted from this recent round of diversification maintain
      relatively high amounts of genetic variation, similar to that of a closely
      related mainland species, and share extensive ancestral polymorphism. These data
      suggest a minimal role for population bottlenecks linked to founder events in the
      history of the D. dunni subgroup. Further, the recent divergence of these island
      populations highlights the extremely rapid development of reproductive isolation
      and distinct patterns of abdominal pigmentation that has occurred in these
      species.

PMID- 14686533
TI  - Genetic dissection of hybrid incompatibilities between Drosophila simulans and D.
      mauritiana. III. Heterogeneous accumulation of hybrid incompatibilities, degree
      of dominance, and implications for Haldane's rule.
AB  - The genetic basis of Haldane's rule was investigated through estimating the
      accumulation of hybrid incompatibilities between Drosophila simulans and D.
      mauritiana by means of introgression. The accumulation of hybrid male sterility
      (HMS) is at least 10 times greater than that of hybrid female sterility (HFS) or
      hybrid lethality (HL). The degree of dominance for HMS and HL in a pure D.
      simulans background is estimated as 0.23-0.29 and 0.33-0.39, respectively; that
      for HL in an F1 background is unlikely to be very small. Evidence obtained here
      was used to test the Turelli-Orr model of Haldane's rule. Composite causes,
      especially, faster-male evolution and recessive hybrid incompatibilities,
      underlie Haldane's rule in heterogametic male taxa such as Drosophila (XY male
      and XX female). However, if faster-male evolution is driven by sexual selection,
      it contradicts Haldane's rule for sterility in heterogametic-female taxa such as
      Lepidoptera (ZW female and ZZ male). The hypothesis of a faster-heterogametic-sex
      evolution seems to fit the current data best. This hypothesis states that
      gametogenesis in the heterogametic sex, instead of in males per se, evolves much
      faster than in the homogametic sex, in part because of sex-ratio selection. This
      hypothesis not only explains Haldane's rule in a simple way, but also suggests
      that genomic conflicts play a major role in evolution and speciation.

PMID- 14686534
TI  - Resistance of spiders to Cretaceous-Tertiary extinction events.
AB  - Throughout Earth history a small number of global catastrophic events leading to
      biotic crises have caused mass extinctions. Here, using a technique that combines
      taxonomic and numerical data, we consider the effects of the Cenomanian-Turonian
      and Cretaceous-Tertiary mass extinctions on the terrestrial spider fauna in the
      light of new fossil data. We provide the first evidence that spiders suffered no
      decline at the family level during these mass extinction events. On the contrary,
      we show that they increased in relative numbers through the Cretaceous and beyond
      the Cretaceous-Tertiary extinction event.

PMID- 14686535
TI  - Sexual selection in female perceptual space: how female tungara frogs perceive
      and respond to complex population variation in acoustic mating signals.
AB  - Female preferences for male mating signals are often evaluated on single
      parameters in isolation or small suites of characters. Most signals, however, are
      composites of many individual parameters. In this study we quantified
      multivariate traits in the advertisement call of the tungara frog, Physalaemus
      pustulosus. We represented the calls in multidimensional scaling space and chose
      nine test calls to represent the range of population variation. We then tested
      females for phonotactic preference between calls in each pair of the nine test
      calls. We used statistics developed for paired comparisons in such "round robin"
      competitions to evaluate the null hypothesis of equal attractiveness, and to
      examine the degree to which females responded to calls as being different from or
      similar to one another in attractiveness. We then examined the attractiveness of
      each test call relative to all other test calls as a function of their location
      in multivariate acoustic space (the acoustic landscape) to visualize sexual
      selection on calls. Finally, we used methods from cognitive psychology to
      illustrate the females' perception of call attractiveness in multivariate space,
      and compared this perceptual landscape to the acoustic landscape of quantitative
      call variation. We show that correlations between individual call characters are
      not strong and thus there are few biomechanical constraints on their independent
      evolution. Most call variables differed among males, and there was high
      repeatability of call characters within males. Females often discriminated
      between pairs of calls from the population, and there were significant
      differences among calls in their attractiveness. Female preferences for calls
      were not stabilizing. The region of the acoustic landscape that was most
      attractive to females included the mean call but was not centered around it. The
      females' perceptual or preference landscape did not correlate with the call's
      acoustic landscape, and female perception of calls decreased rather than enhanced
      call differences.

PMID- 14686536
TI  - The Australian scincid lizard Menetia greyii: a new instance of widespread
      vertebrate parthenogenesis.
AB  - Molecular data derived from allozymes and mitochondrial nucleotide sequences, in
      combination with karyotypes, sex ratios, and inheritance data, have revealed the
      widespread Australian lizard Menetia greyii to be a complex of sexual and
      triploid unisexual taxa. Three sexual species, three presumed parthenogenetic
      lineages, and one animal of uncertain status were detected amongst 145 animals
      examined from south-central Australia, an area representing less than one-seventh
      of the total distribution of the complex. Parthenogenesis appears to have
      originated via interspecific hybridization, although presumed sexual ancestors
      could only be identified in two cases. The allozyme and mtDNA data reveal the
      presence of many distinct clones within the presumed parthenogenetic lineages.
      This new instance of vertebrate parthenogenesis is a first for the Scincidae and
      only the second definitive case of unisexuality in an indigenous Australian
      vertebrate.

PMID- 14686537
TI  - Natural selection on protein polymorphism in the rodent genus Peromyscus:
      evidence from interlocus contrasts.
AB  - The effects of natural selection are generally locus-specific, whereas migration,
      drift, and inbreeding are expected to have relatively uniform effects across the
      entire genome. This suggests that multilocus surveys of multiple populations can
      be used to distinguish selection from demographic effects. The purpose of this
      study was to test for evidence of selection on protein polymorphism in natural
      populations of mice in the genus Peromyscus. We analyzed published data from
      geographic surveys of allozyme variation and used a coalescent-based simulation
      model to identify specific loci that deviated from neutral expectations. Observed
      F(ST) values generally exhibited a remarkably close fit to the expected neutral
      distributions, indicating that the majority of loci are simply tracking
      stochastic demographic processes. A smaller number of loci exhibited highly
      significant departures from the expectations of the neutral model and thus appear
      to be tracking the direct or indirect effects of selection. Most departures from
      neutrality were characterized by F(ST) values that far exceeded neutral
      expectations and were therefore attributable to spatially varying selection.
      Interestingly, the albumin locus was implicated as a candidate gene for local
      adaptation in four different species of Peromyscus. The results also demonstrate
      that selection can severely bias marker-based estimates of neutral parameters.

PMID- 14686538
TI  - Evolution and function of routine trichromatic vision in primates.
AB  - Evolution of the red-green visual subsystem in trichromatic primates has been
      linked to foraging advantages, namely the detection of either ripe fruits or
      young leaves amid mature foliage. We tested competing hypotheses globally for
      eight primate taxa: five with routine trichromatic vision, three without.
      Routinely trichromatic species ingested leaves that were "red shifted" compared
      to background foliage more frequently than species lacking this trait. Observed
      choices were not the reddest possible, suggesting a preference for optimal
      nutritive gain. There were no similar differences for fruits although red
      greenness may sometimes be important in close-range fruit selection. These
      results suggest that routine trichromacy evolved in a context in which leaf
      consumption was critical.

PMID- 14686539
TI  - On the persistence and pervasiveness of a new mutation.
AB  - It has frequently been assumed that the persistence of a deleterious mutation
      (the average number of generations before its loss) and its pervasiveness (the
      average number of individuals carrying the gene before its loss) are equal. This
      is true for a particular simple, widely used infinite model, but this agreement
      is not general. If hs >> 1/(4N(e)), where hs is the selective disadvantage of
      mutant heterozygotes and N(e) is the effective population number, the
      contribution of homozygous mutants can be neglected and the simple approximate
      formula 1/hs gives the mean pervasiveness. But the expected persistence is
      usually much smaller, 2(log(e)(1/2hs) + 1 - gamma) where gamma = 0.5772. For
      neutral mutations, the total number of heterozygotes until fixation or loss is
      often the quantity of interest, and its expected value is 2N(e), with remarkable
      generality for various population structures. In contrast, the number of
      generations until fixation or loss, 2(N(e)/N)(1 + log(e)2N), is much smaller than
      the total number of heterozygotes. In general the number of generations is less
      than the number of individuals.

PMID- 14686540
TI  - Quantifying phylogenetically structured environmental variation.
AB  - Comparative analysis methods control for the variation linked to phylogeny before
      attempting to correlate the remaining variation of a trait to present-day
      conditions (i.e., ecology and/or environment). A portion of the phylogenetic
      variation of the trait may be related to ecology, however; this portion is called
      "phylogenetic niche conservatism." We propose a method of variation partitioning
      that allows users to quantify this portion of the variation, called the
      "phylogenetically structured environmental variation." The new method is applied
      to published data to study, in a phylogenetic framework, the link between body
      mass and population density in 79 species of mammals. The results suggest that an
      important part of the variation of mammal body mass is related to the common
      influence of phylogeny and population density.

PMID- 14686542
TI  - Genetic variation of sex allocation in the parasitoid wasp Heterospilus
      prosopidis.
AB  - The genetic variation of sex ratio and sex allocation were examined in a series
      of half-sib analyses on the sex ratio of braconid parasitoid wasp Heterospilus
      prosopidis populations collected in Hawaii and Arizona. The mean threshold value
      and the range of the threshold for change in the sex of offspring in response to
      resource quality (host size) were determined. Estimates of the narrow-sense
      heritability (h2) of sex ratio at a specific host size ranged from 0.185 to
      0.315, and those of the sex changing point (threshold value) ranged from 0.220 to
      0.342. The coefficient of variation (CV(A)) of sex ratio was significantly larger
      than CV(A) of body weight. We discuss factors that maintained the significant
      additive genetic variation of sex ratio.

PMID- 14686541
TI  - QTL mapping reveals a striking coincidence in the positions of genomic regions
      associated with adaptive variation in body size in parallel clines of Drosophila
      melanogaster on different continents.
AB  - Latitudinal genetic clines in body size are common in many ectotherm species and
      are attributed to climatic adaptation. Here, we use Quantitative Trait Loci (QTL)
      mapping to identify genomic regions associated with adaptive variation in body
      size in natural populations of Drosophila melanogaster from extreme ends of a
      cline in South America. Our results show that there is a significant association
      between the positions of QTL with strong effects on wing area in South America
      and those previously reported in a QTL mapping study of Australian cline end
      populations (P < 0.05). In both continents, the right arm of the third chromosome
      is associated with QTL with the strongest effect on wing area. We also show that
      QTL peaks for wing area and thorax length are associated with the same genomic
      regions, indicating that the clinal variation in the body size traits may have a
      similar genetic basis. The consistency of the results found for the South
      American and Australian cline end populations indicate that the genetic basis of
      the two clines may be similar and future efforts to identify the genes producing
      the response to selection should be focused on the genomic regions highlighted by
      the present work.

PMID- 14686543
TI  - Source and filter adjustments affecting the perception of the vocal qualities
      twang and yawn.
AB  - Two vocal qualities, twang and yawn, were synthesized and rated perceptually. The
      stimuli consisted of synthesized vocal productions of a sentence-length utterance
      'ya ya ya ya ya,' which had speech-like intonation. In a continuum transformation
      from normal to twang, the area in the pharynx was gradually decreased, along with
      vocal tract shortening and a decreased open quotient in the glottal airflow. In a
      continuum transformation toward yawn, the area in the pharynx was gradually
      increased, along with vocal tract lengthening and an increased open quotient. The
      normal (untransformed) vocal tract area was pre-determined by earlier studies
      involving MRI scans of a human subject's vocal tract. Listeners were asked to
      rate (on a scale from 1-10) the 'amount of twang' in one listening session and
      the 'amount of yawn' in another listening session. Overall, the perception of
      twang increased directly with pharyngeal area narrowing, vocal tract shortening,
      and decreased open quotient. The perception of yawn increased with pharyngeal
      area widening, vocal tract lengthening, and increased open quotient. Adjustments
      of one parameter alone yielded less significant perceptual changes than the above
      combinations, with open quotient showing the greatest effect in isolation.
      Listeners demonstrated variable perceptions in both continua with poor inter
      subject, intra-subject, and inter-group reliability.

PMID- 14686544
TI  - Towards assessment of prosodic abilities in Swedish children with language
      impairment.
AB  - Swedish children with language impairment (LI) have prosodic problems at word and
      phrase level, possibly also at discourse level. The aim of this study was to
      investigate the reliability and validity of a newly developed comprehensive
      procedure to capture prosody at word level (e.g., tonal word accent), phrase
      level (e.g., copula) and discourse level (e.g., conversation) in Swedish children
      with LI. Twenty-nine children with LI participated in the study. The reliability
      of the total score of the procedure was found to be sufficiently high, as was
      inter-examiner agreement. The total score significantly correlated with language
      comprehension and grammatical abilities. Prosodic problems were found by
      perceptual assessment in one third of the children. t test for equality of
      variances for presence versus absence of prosodic problems showed that these two
      groups significantly differed in total score of the procedure. This indicates
      that the procedure is a valid measure of prosodic problems.

PMID- 14686545
TI  - Defining 'open throat' through content analysis of experts' pedagogical
      practices.
AB  - 'Open throat' is a term regularly used in the singing studio, but agreement
      across pedagogues as to its definition and function has not yet been assessed.
      Fifteen expert singing pedagogues participated in a qualitative study involving a
      semi-structured interview to explore current thinking regarding terminology,
      pedagogy, sound quality and the perceived physiology to achieve open throat, as
      used in the singing studio. Most teachers included the use of the technique as a
      fundamental in singing training, and were positive about the sound quality it
      achieved, especially in classical singing. The purpose of the technique was
      described as a way of maximizing pharyngeal space and/or achieving abduction of
      the ventricular folds.

PMID- 14686546
TI  - Measurement of vocal doses in speech: experimental procedure and signal
      processing.
AB  - An experimental method for quantifying the amount of voicing over time is
      described in a tutorial manner. A new procedure for obtaining calibrated sound
      pressure levels (SPL) of speech from a head-mounted microphone is offered. An
      algorithm for voicing detection (kv) and fundamental frequency (F0) extraction
      from an electroglottographic signal is described. The extracted values of SPL,
      F0, and kv are used to derive five vocal doses: the time dose (total voicing
      time), the cycle dose (total number of vocal fold oscillatory cycles), the
      distance dose (total distance travelled by the vocal folds in an oscillatory
      path), the energy dissipation dose (total amount of heat energy dissipated in the
      vocal folds) and the radiated energy dose (total acoustic energy radiated from
      the mouth). The doses measure the vocal load and can be used for studying the
      effects of vocal fold tissue exposure to vibration.

PMID- 14686547
TI  - Management of sickle cell disease in primary care.

PMID- 14686548
TI  - Medical screening of immigrant children.

PMID- 14686549
TI  - Environmental tobacco smoke exposure in pediatric asthma: overview and
      recommendations for practice.

PMID- 14686550
TI  - Feedback on a multimedia violence prevention program.
AB  - The objective of this study is to describe feedback on a multimedia violence
      prevention program. Professionals and laypersons provided feedback regarding a
      multimedia CD program by completing an anonymous form. Feedback was obtained from
      66% of participants (314). In general, participants felt more comfortable
      managing childhood aggression after the program (p<0.001). Pediatric residents
      felt more comfortable counseling parents (p<0.001). Approximately 90% of
      participants would either strongly or very strongly recommend the program to
      others. Multimedia programs can increase comfort level with managing childhood
      aggression, suggesting that they hold promise for use as adjunctive violence
      prevention tools.

PMID- 14686551
TI  - A comparison of time to positive culture and time to clinical identification of
      serious bacterial infection in infants.
AB  - To compare the time to positive culture with the time to clinical detection of
      serious bacterial infection (SBI) in young infants, a retrospective case series
      of 949 infants age 0-60 days, who had a body fluid cultured in the emergency
      department or within 24 hours of admission was analyzed. Times to first report of
      positive culture and first clinical diagnosis of SBI were compared. Of 44 infants
      with positive cultures, 48% were clinically diagnosed with SBI at first
      evaluation. Of 21 infants with cultures reported positive after 24 hours, 14 were
      already diagnosed with SBI. Infections that altered therapy were identified after
      24 and 36 hours in 4 infants and 1 infant, respectively. In infants with SBIs,
      the time to positive culture is longer than the time to identification of
      infection.

PMID- 14686552
TI  - Clinical and parental assessment of sleep in children with attention
      deficit/hyperactivity disorder referred to a pediatric sleep medicine center.
AB  - Frequently reported sleep problems in children with attention deficit
      hyperactivity disorder (ADHD) referred to a pediatric sleep medicine center were
      assessed and compared with objective sleep assessments. A retrospective review of
      97 children with ADHD (mean age of 8.3+/-3.0 years) was conducted.
      Polysomnography in 69 children revealed periodic limb movement disorder (PLMD) in
      36% and sleep-disordered breathing in 7%, while actigraphy uncovered substantial
      variability in sleep schedules of 16 patients. Although parental subjective sleep
      complaints were verified by objective sleep assessments in a small proportion of
      cases, PLMD and night-to-night variability in sleep patterns were common.

PMID- 14686553
TI  - Long-term efficacy of polyethylene glycol 3350 for the treatment of chronic
      constipation in children with and without encopresis.
AB  - Seventy-four children (43 with chronic constipation, 31 with constipation and
      encopresis) treated with polyethylene glycol 3350 (PEG) for longer than 3 months
      were studied to assess long-term efficacy. The mean duration of PEG therapy was
      8.4 months (range, 3-30). Weekly stool frequency, stool consistency, and symptoms
      associated with constipation improved significantly with PEG therapy in all 74
      patients. In 31 children with encopresis, soiling ceased completely in 16
      patients and frequency of soiling decreased significantly in all others. The
      average effective long-term dose of PEG was 0.7 g/kg/day. Long-term PEG therapy
      is effective for the treatment of chronic constipation with and without
      encopresis in children.

PMID- 14686554
TI  - Administration of palivizumab: a medical provider's perspective.

PMID- 14686555
TI  - Swollen upper extremities.

PMID- 14686556
TI  - Congenital pulmonary lymphangiectasis.

PMID- 14686557
TI  - Is this patient insulin resistant? How much does it matter?
AB  - Alex was an obese 10-year-old girl with a family history of type 2 diabetes,
      hypertension, and perhaps polycystic ovarian syndrome. Her physical examination
      was significant for a central accumulation of body fat and acanthosis nigricans.
      Although the laboratory studies indicated that Alex was not diabetic and probably
      not glucose intolerant, she could be insulin resistant (IR). Should any further
      evaluation be done? If Alex is IR, what kind of treatment should be offered? The
      following discussion addresses these questions by reviewing the pathophysiology,
      diagnosis, and consequences of isolated IR.

PMID- 14686558
TI  - Maturational delay is not a cause of bedwetting.

PMID- 14686559
TI  - Erectile dysfunction: a window of opportunity for preventing vascular disease?

PMID- 14686560
TI  - Reporting suspected adverse drug reactions: the importance of providing full and
      accurate data.

PMID- 14686561
TI  - Statins: is OTC actually OTT?

PMID- 14686562
TI  - Efficacy of povidone-iodine in preputial antisepsis.
AB  - Wound infection after a surgical procedure is one of the main problems affecting
      the success of an operation. The prepuce is used in hypospadias surgery and in
      tissue defects in reconstructive surgery. The objective of this study is to
      determine the efficacy of povidone-iodine and surgical soap in preputial skin
      preparation. Ninety-four healthy children were divided into three groups. After
      obtaining preputial skin swabs, an application of povidone-iodine 10% was made
      and skin swabs were obtained after two and five minutes in group 1. An additional
      application of povidone-iodine after two minutes was made in group 2 and swabs
      taken. Group 3 received a local scrub with surgical soap and an application of
      povidone-iodine. Results showed that, despite painting with povidone-iodine
      and/or local cleaning with surgical soap, it is not possible totally to eradicate
      the micro-organisms in the prepuce. Surgical soap decreases the colony count,
      which can lead to increased effectiveness of povidone-iodine after painting. We
      recommend preoperative local cleaning with surgical soap before surgical
      painting.

PMID- 14686563
TI  - Potential long-term effects of rivastigmine on disease progression may be linked
      to drug effects on vascular changes in Alzheimer brains.
AB  - Alzheimer's disease patients with hypertension or other vascular risk factors
      have been shown to receive greater symptomatic benefits than patients with
      strictly Alzheimer's disease following short-term treatment with rivastigmine, an
      inhibitor of acetylcholinesterase and butyrylcholinesterase. We evaluated the
      long-term efficacy of rivastigmine in Alzheimer's disease patients with or
      without hypertension. Subjects in a 26-week placebo-controlled trial of
      rivastigmine entered an open-label extension study for 104 weeks. Efficacy
      measures included the Alzheimer's Disease Assessment Scale-cognitive subscale
      (ADAS-cog), Progressive Deterioration Scale (PDS) and Global Deterioration Scale
      (GDS). Subjects were stratified by the presence or absence of hypertension at
      baseline. At 104 weeks, there was a trend for hypertensive patients from the
      original rivastigmine 6-12 mg/day group (early starters), who received
      rivastigmine for the full 104 weeks) to have better ADAS-cog scores than the
      original placebo group (late starters), who received open-label rivastigmine for
      the last 78 weeks only). Significant treatment differences were observed in the
      hypertensive subgroup on the PDS and GDS. In non-hypertensive patients, changes
      from baseline at week 104 were similar in 'early' and 'late' starters of
      rivastigmine treatment. The additional apparent benefits on disease progression
      detected in patients with hypertension and Alzheimer's disease may be linked to
      drug effects on cerebrovascular factors. These findings may have an important
      influence on the way cholinesterase inhibitors are prescribed.

PMID- 14686564
TI  - Patient-reported benefits of rizatriptan compared with usual non-triptan therapy
      for migraine in a primary care setting.
AB  - The purpose of this open-label study was to compare rizatriptan with usual non
      triptan therapy for migraine in patients who had never received a triptan.
      Patient-reported outcomes were examined for a prestudy migraine attack and after
      three consecutive study attacks, the first and third treated with rizatriptan 10
      mg wafer and the second with usual non-triptan therapy. A total of 97 patients
      (83% women; mean age 39 years) completed the study. Two-thirds of patients
      reported severe or total disability during migraine attacks. All comparisons
      between rizatriptan therapy and usual non-triptan therapy significantly favoured
      rizatriptan (p < or = 0.01). Headache relief by 2 hours was reported by 78-83% of
      patients after rizatriptan and by 46-48% of patients after usual therapy; 41-47%
      and 12-18%, respectively, were pain free at 2 hours. Patient satisfaction and
      migraine-specific quality-of-life scores were also significantly better for
      attacks treated with rizatriptan. At study end, 62% and 17% of patients were very
      or completely satisfied with rizatriptan and usual non-triptan therapy,
      respectively. Among those patients who worked for pay, therapy with rizatriptan
      significantly reduced absenteeism and improved the amount and quality of time at
      work compared with usual non-triptan therapy. Allowing patients to have
      experience with rizatriptan may improve the level of medical care for migraine
      attacks.

PMID- 14686565
TI  - Efficacy of radiofrequency volumetric tissue reduction of the soft palate in the
      treatment of snoring.
AB  - Traditional surgery for snoring often leads to intolerable postoperative pain. A
      new surgical treatment, radiofrequency volumetric tissue reduction (RVTR) of the
      soft palate, was carried out and its effect and safety in the management of
      snoring were evaluated. Thirty-two patients received a single treatment of RVTR
      with a mean follow-up period of 4.5 months. All patients were assessed by a
      questionnaire using the Snore Outcomes Survey (SOS) and the Epworth Sleepiness
      Scale (ESS). Postoperative pain, speech and swallowing disturbances were also
      evaluated. The postoperative scores of SOS and ESS all significantly improved
      (p<0.05). Postoperative pain, speech and swallowing disturbances were all mild 1
      3 days after treatment. With the success of treatment defined as a postoperative
      snoring index (SI) of <3 or a reduction of the SI by >5 points by the visual
      analogue scale, the success rate was 81.3% in patients with a respiratory
      disturbance index (RDI) of <20, and 50% in those with an RDI of >20. We conclude
      that RVTR of the soft palate is an effective treatment for snoring, resulting in
      only mild postoperative discomfort. A patient whose RDI was <20 had a higher
      success rate with a single RVTR treatment.

PMID- 14686566
TI  - A national survey of transrectal ultrasound-guided prostatic biopsies: time for a
      national guideline.
AB  - The aim of this study was to elicit similarities and differences in transrectal
      ultrasound guided prostatic biopsy regimens in the UK and the Republic of
      Ireland. A telephone survey of 60 centres was conducted and information collected
      on the operator, the anaesthesia used, antibiotic prophylaxis and number of
      biopsies taken. Most prostatic biopsies were performed by urologists and most
      procedures involved six cores. There was a marked variation in the use of
      antibiotic prophylaxis, and anaesthesia was used sparingly. Our survey has shown
      a diversity in protocols used in transrectal ultrasound guided biopsies in the UK
      and Ireland. It seems sensible to standardise the technique for optimal patient
      satisfaction, as well as clinical efficiency. A national co-ordinated,
      prospective trial is needed.

PMID- 14686567
TI  - Persistent otorrhoea after ventilation tube insertion: a treatment protocol.
AB  - Otorrhoea is the commonest complication of ventilation tube (grommet) insertion.
      In some cases it may be unresponsive to short courses of topical
      antibiotic/steroid drops and/or systemic antibiotics. This study investigated
      whether a five-day course of inpatient treatment with intravenous antibiotics,
      topical medication and daily microsuction was effective in treating persistent
      otorrhoea. Eleven subjects were included, of whom nine responded to the proposed
      treatment regimen. We recommend that patients with persistent otorrhoea after
      ventilation tube insertion should be managed according to these guidelines before
      considering an examination under anaesthetic or a ventilation tube removal.

PMID- 14686568
TI  - Acute acalculous cholecystitis in China.
AB  - In order to study the clinical characteristics of patients with acute acalculous
      cholecystitis (AAC) in China, we retrospectively analysed the epidemiology,
      clinical manifestations and treatment of hospitalised cases with AAC in our
      hospital between January 1991 and October 1998, and compared the results with
      western reports. Most AAC cases in our series were younger than 60 years, and
      there was no significant difference between males and females. Their clinical
      manifestations were usually not serious. Only one patient suffered complications.
      The rate of complications and mortality was lower than those in western
      countries. All patients were treated and recovered; none needed an emergency
      operation and there were no deaths.

PMID- 14686569
TI  - Sleep disorders in Parkinson's disease.
AB  - Sleep quality is one of the major sources of dissatisfaction among patients with
      Parkinson's disease (PD). Insomnia, parasomnia and daytime sleep disorders are
      all common. The motor problems accompanying PD are well studied and documented,
      yet little is known about sleep and the other non-motor problems. Dopaminergic
      medications, the neurochemical and neurodegenerative changes may all contribute
      to the pathogenesis of sleep disorders in PD. Subjective or objective sleepiness
      assessment should routinely be performed by physicians looking after PD patients.
      Patients should be informed of the risks associated with excessive daytime
      sleepiness. Management is difficult and should be targeted to the specific sleep
      disorder and its likely cause. Simple sleep measures such as sleep hygiene should
      be tried first before pharmacological treatment is initiated.

PMID- 14686570
TI  - Snoring, not just a social nuisance.
AB  - Snoring is a very common source of complaints from partners and neighbours.
      Snorers themselves are less likely to be affected, unless they have associated
      daytime sleepiness caused by the sleep disruption from obstructive sleep apnoea.
      There is increasingly firm evidence that obstructive sleep apnoea is associated
      with hypertension, cardiovascular, cerebrovascular and metabolic problems such as
      insulin resistance, even at mild levels which may not cause much daytime
      somnolence. In addition, the central and obstructive apnoeas found in cardiac
      failure affect heart muscle function. Treatment of the apnoea improves blood
      pressure and cardiac function and is likely to have a beneficial effect on
      mortality. Since obstructive sleep apnoea is common it should be sought by
      appropriate questioning in these patient groups. The treatments for obstructive
      sleep apnoea are effective but cumbersome and this remains a challenge if
      patients do not achieve obvious early benefits such as reduction in sleepiness or
      breathlessness.

PMID- 14686571
TI  - The cost-effectiveness of a new statin (rosuvastatin) in the UK NHS.
AB  - Statins are central to the government's National Service Framework (NSF) for
      coronary heart disease (CHD). NHS spending on statins is currently about pounds
      sterling 500 million per annum and rising at an annual rate of 30%. Although
      generally considered to be a cost-effective treatment for hyperlipidaemia and
      cardiovascular disease, given the high and rising expenditure on statins in the
      UK, there is a pressing need to ensure that the choice between available statins
      reflects cost-effectiveness considerations. A decision model was developed to
      establish the cost-effectiveness of treating new hypercholesterolaemic patients
      to UK and European target levels of blood total cholesterol (TC) and low density
      lipoprotein-cholesterol (LDL-C), using rosuvastatin, atorvastatin, simvastatin,
      pravastatin or fluvastatin. The model was used to estimate the proportion of
      patients reaching target and the associated costs over a one-year period from the
      perspective of the NHS. The effectiveness of the alternative statins were
      modelled using data from the Statin Therapies for Elevated Lipid Levels compared
      Across doses to Rosuvastatin (STELLAR) trial. Monte Carlo simulation was used to
      reflect uncertainty in the parameter estimates applied in the model. Rosuvastatin
      is demonstrated to dominate (i.e. lower costs and a higher number of patients
      treated to target) atorvastatin, simvastatin and pravastatin. Compared with
      fluvastatin, the incremental cost per additional patient to target (PTT) for
      rosuvastatin was pounds sterling 24 using LDL-C and pounds sterling 83 using TC.
      The probability that rosuvastatin is cost-effective exceeds 95%, provided the NHS
      is prepared to pay at least pounds sterling 35 per PTT to achieve target LDL-C
      cholesterol levels (pounds sterling 160 for TC). The analysis demonstrates
      rosuvastatin is more cost-effective than the other statins in achieving UK and
      European cholesterol targets.

PMID- 14686572
TI  - Therapeutic effects of angiotensin II inhibition or blockade on the progression
      of chronic renal disease.
AB  - Experimental and clinical research has supported the use of angiotensin
      converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in
      diabetic, hypertensive and proteinuric nephropathies. This review will evaluate
      the role of angiotensin II in the progression of renal damage in kidney diseases;
      the diagnostic value of microalbuminuria as an early clinical sign of renal
      damage and the possibility of preventing its further progression; the clinical
      results obtained with ACE inhibitors and/or ARBs in diabetic and non-diabetic
      nephropathies; and the therapeutic possibilities of ACE inhibitors and ARBs in
      renal transplantation. Based on available clinical data, ACE inhibitors can be
      considered to be the gold standard in reducing and/or preventing albuminuria, and
      thereby decreasing the percentage of patients who will progress to end-stage
      renal disease and death. Renal transplantation and chronic allograft nephropathy
      appear to be a promising field for the use of ACE inhibitors and ARBs.

PMID- 14686573
TI  - Levonorgestrel as an emergency contraceptive drug.
AB  - The potential of low-dose levonorgestrel, alone or in combination with
      ethynyloestradiol (Yuzpe regimen), as emergency contraception is reviewed for its
      acceptability and effectiveness. Plasma levonorgestrel concentration ranges from
      9-12 nmol/l at 12 hours with a peak of 27-33 nmol/l 2-2.5 hours after taking one
      0.75 mg tablet. The concentration of steroid hormone binding globulins in plasma
      is not influenced by the presence of levonorgestrel during this period. The
      success rates for levonorgestrel-only and the Yuzpe regimen as emergency
      contraception are 85% and 57%, respectively, while the failure rates are 1.1% and
      3.2%, respectively, within the prescribed time limit of use. The mode of action
      of levonorgestrel emergency contraception is to prevent or delay ovulation and/or
      alter the endometrium unfavourably the for implantation of an embryo. The use of
      emergency contraceptive pills within 72 hours after unprotected sexual
      intercourse reduces the risk of pregnancy by about 75% and is safe, with no
      serious side-effects.

PMID- 14686574
TI  - Unintentional rechallenge resulting in a causative relationship between
      ketoconazole and acute liver injury.
AB  - We present the case of a female patient in whom acute overt hepatitis developed
      after 60 days of ketoconazole administration (200 mg/day). A prompt renewed
      hepatic injury 48 hours after an unintentional rechallenge 30 months later
      provided definitive evidence for a causative relationship between ketoconazole
      and acute liver injury. Histological examination revealed acute hepatitis with
      bridging hepatic necrosis. Clinicians should be aware of this cause and effect
      relationship between ketoconazole and acute liver injury, which can result in
      prompt severe acute liver injury after rechallenge.

PMID- 14686575
TI  - Excitability of the motor cortex in schizophrenia following typical and atypical
      antipsychotics: two serial case reports.
AB  - A previous electrophysiological investigation of schizophrenia using transcranial
      magnetic stimulation has shown altered corticospinal inhibition in medicated
      patients compared with drug-naive patients. Based on this work, we have carried
      out the first serial electrophysiological case studies of the human corticospinal
      system in schizophrenia in which a typical antipsychotic was compared with an
      atypical antipsychotic. We used transcranial magnetic stimulation-based
      techniques to study the time course of drug action in two antipsychotic drug
      naive patients with schizophrenia; one patient treated with a typical
      antipsychotic (haloperidol) and the other with an atypical antipsychotic
      (risperidone). The typical antipsychotic was associated with an increase in
      corticospinal excitability which we found to occur 4-5 weeks after beginning
      medication. In contrast, the atypical antipsychotic was associated with a
      decrease in corticospinal excitability, occurring 3-4 weeks after starting
      pharmacotherapy. We conclude that these opposite neurophysiological effects are
      related to the relative dopaminergic and serotonergic actions of the two classes
      of drug.

PMID- 14686576
TI  - Patient satisfaction with conventional and nurse-led telephone follow-up after
      nasal septal surgery.
AB  - The need to bring down costs while maintaining a high standard of care has led to
      the expansion in the role of nurses in recent years. We present results of an
      audit of patient satisfaction with conventional and nurse-led telephone follow-up
      after nasal septal surgery. Our results indicate that patient satisfaction with
      nurse-led telephone follow-up is significantly higher than conventional follow-up
      (p=0.001, two-tailed). More patients in the conventional follow-up group felt
      that a follow-up appointment with an ENT doctor was essential compared with the
      patients in the nurse-led telephone follow-up group (p<0.001, two-tailed). We
      conclude that nurse-led telephone follow-up avoids unnecessary outpatient
      appointments, while identifying patients who require further care. It makes more
      appointment slots available for patients with pressing clinical problems and has
      the potential to reduce outpatient access times in the NHS.

PMID- 14686577
TI  - Addisonian crisis due to adrenal gland metastasis in Hodgkin's disease.
AB  - Adrenal insufficiency or Addison's disease is a rare illness associated with
      multiple pathology. We describe the case of a 61-year-old male with Hodgkin's
      disease and metastases in both adrenal glands who was diagnosed with adrenal
      insufficiency as a result of an acute addisonian crisis.

PMID- 14686578
TI  - Phaeochromocytoma-induced myocarditis mimicking acute myocardial infarction.
AB  - A 44-year-old woman presented with sudden onset of chest pain, headache and
      nausea. Physical examination was remarkable for mild hypotension and tachycardia.
      ECG demonstrated sinus tachycardia with poor R wave progression in precordial
      leads and T wave inversion in leads V1-3. Cardiac enzymes were raised.
      Echocardiographic examination revealed normal cavity diameters with basal and mid
      left ventricular hypokinesia and an ejection fraction of 45%. A diagnosis of non
      ST elevation myocardial infarction was made. A few orthostatic hypotensive
      attacks occurred at follow-up. A coronary angiogram showed normal coronary
      arteries. Within a few days, the echocardiographic findings, ECG and all cardiac
      markers had returned to normal. Two months later she presented with headache,
      palpitation, fever, neck swelling, flushing and hypertensive attacks.
      Phaeochromocytoma was diagnosed on the basis of increased metanephrine on
      urinalysis and a left suprarenal mass on CT scan.

PMID- 14686579
TI  - XX male: a rare cause of short stature, infertility, gynaecomastia and carcinoma
      of the breast.
AB  - We present a case of an XX male with carcinoma of the breast and primary
      infertility. He was admitted to hospital with recurrent chest pains, but a
      history of surgery for breast carcinoma, gynaecomastia and the finding of
      bilaterally atrophied testes, coupled with the fact that he had never fathered
      children, necessitated further investigations. Chromosomal analysis showed a 46,
      XX male genotype with a normal X chromosome and an abnormal X chromosome formed
      by translocation between the short arm of one X chromosome and the Y chromosome.
      By using fluorescence in situ hybridisation, the patient proved to be SRY
      positive, the sex-determining region of the Y chromosome. In this rare genetic
      abnormality, males retain normal phenotype but they are generally of short
      stature, have gynaecomastia, and may have genital anomalies. They are infertile
      and at increased risk of developing carcinoma of the breast. This seems to be the
      first documented case of carcinoma of the breast in an SRY positive XX male. This
      particular case illustrates the need for all cases of male breast cancer to
      undergo full endocrinological assessment, especially in the presence of genital
      anomaly or infertility.

PMID- 14686580
TI  - A spinal neurenteric cyst presenting as burning feet syndrome.
AB  - Spinal neurenteric cysts are rare congenital cysts of endodermal origin. A 34
      year-old man presented with burning feet syndrome lasting two years. Magnetic
      resonance imaging (MRI) revealed an intradural extramedullary cystic mass
      extending from L2 to L5 causing severe compression of the terminal portion of the
      conus medullaris and the filum terminale with displacement to the right side. A
      tethered cord and filar lipoma were also present. The cystic mass and filar
      lipoma were resected and the tethered cord released. Histopathology confirmed a
      neurenteric cyst. This case is reported in view of its peculiar presentation.

PMID- 14686581
TI  - Intratesticular cysts and malignant potential: conservative management is an
      option.
AB  - Benign intratesticular cysts are rare, but recognition is essential to prevent
      unnecessary surgical intervention. The diagnostic dilemma is to differentiate
      these cysts from testicular malignancy. As they are extremely uncommon,
      experience of their management is limited and controversial. We present a case of
      a simple intratesticular cyst and discuss the diagnostic and management
      principles.

PMID- 14686582
TI  - Identification and sequence of seventy-nine new transcripts expressed in
      hemocytes of Ciona intestinalis, three of which may be involved in characteristic
      cell-cell communication.
AB  - Ascidian is a useful experimental animal for studying body planning principles
      and host defense mechanisms employed by the phylum chordata. Toward this goal,
      genome and cDNA/EST projects of Ciona intestinalis have been undertaken. Using
      cDNAs and ESTs derived from Ciona hemocytes, we identified 79 possible hemocyte
      preferential transcripts and determined the cDNA sequence of each clone. The
      amino acid sequence of each encoded polypeptide was predicted as well. Among
      these cDNAs, we identified three transcripts that may be involved in
      characteristic cell-cell communication in Ciona. These transcripts encoded
      leucine-rich repeat-containing RP105-like, IL-17 receptor/similar expression to
      FGF-like, and ectodysplasin-like polypeptide of the tunmr necrosis factor famlly,
      and they are expressed abundantly in hemocytes.

PMID- 14686583
TI  - CCLS96.1, a member of a multicopy gene family, may encode a non-coding RNA
      preferentially transcribed in reproductive organs of Silene latifolia.
AB  - Dioecy in the model dioecious plant Silene latifolia is determined genetically by
      its heteromorphic sex chromosomes. A bacterial artificial chromosome (BAC) clone,
      #19B12, was isolated by screening a BAC library from S. latifolia using
      polymerase chain reaction (PCR) with a set of sequence tagged site (STS) primers,
      ScD05, which are specific to the Y chromosome. A portion of #19B12 was subcloned
      to construct plasmid #25-1, with an insert of 7.8 kb. This 7.8-kb fragment
      encodes ScD05 homolog and an anther-specific gene, CCLS96.1. Northern blot
      analysis of CCLS96.1 indicated a faint band of 1.8 kb in male and female flower
      buds. 5' and 3' rapid amplification of cDNA ends (RACE) indicated that
      transcripts of CCLS96.1 are very varied in size. Moreover, semi-quantitative
      reverse transcription-PCR (RT-PCR) showed that CCLS96.1 was also expressed in
      both male and female leaves. RACE produced at least ten species of transcripts,
      with 79-97% similarity among them. However, no significant ORFs could be
      predicted from their nucleotide sequences, since each has numerous stop codons
      throughout all three reading frames. Genomic Southern hybridization showed that
      the S. latifolia genome contains numerous CCLS96.1 homologs. These results
      suggest that the transcripts of CCLS96.1 play some role as multiple non-coding
      RNAs in S. latifolia.

PMID- 14686584
TI  - Structural analysis of four large plasmids harboring in a unicellular
      cyanobacterium, Synechocystis sp. PCC 6803.
AB  - The genome of the unicellular cyanobacterium Synechocystis sp. PCC 6803 consists
      of a single chromosome and several plasmids of different sizes, and the
      nucleotide sequences of the chromosome and three small plasmids (5.2 kb, 2.4 kb,
      and 2.3 kb) have already been sequenced. We newly determined the nucleotide
      sequences of four large plasmids, which have been identified in our laboratory
      (pSYSM:120 kb, pSYSX:106 kb, pSYSA:103 kb, and pSYSG:44 kb). Computer-aided
      analysis was performed to explore the genetic information carried by these
      plasmids. A total of 397 potential protein-encoding genes were predicted, but
      little information was obtained about the functional relationship of plasmids to
      host cell, as a large portion of the predicted genes (77%) were of unknown
      function. The occurrence of the potential genes on plasmids was divergent, and
      parA was the only gene common to all four large plasmids. The distribution data
      of a Cyanobacterium-specific sequence (HIP1: 5'-GCGATCGC-3') suggested that
      respective plasmids could have originated from different cyanobacterial strains.

PMID- 14686585
TI  - Wigner-Ville analysis and classification of electrocardiograms during
      thrombolysis.
AB  - Non-stationary analysis of electrocardiograms (ECGs) using Wigner-Ville
      distribution is presented. Analysis was performed on subjects with acute
      myocardial infarction who had undergone thrombolysis, in Holter recordings of
      lead V1. The distinction between successfully and non-successfully thrombolysed
      patients was evaluated, based on time-frequency features of the Wigner-Ville
      transformed ECGs at the sixth hour after lysis. Characteristic parameters were
      extracted from time-frequency areas, and linear discriminant analysis was
      performed on these parameters, leading to a prediction index to distinguish the
      two classes. Thirteen features were found statistically significant by t-test and
      were used for the classification with linear modelling. Out of these features,
      four corresponded to frequencies lower than 25 Hz and higher than 50 Hz for,
      roughly, the QRS complex, five features corresponded to all the frequency bands
      of, roughly, the ST area, and the last four features corresponded to the T-wave.
      The feature-vector used in linear modelling was iteratively generated, and the
      iterative prediction found all 18 features significant. The iterative method
      resulted in better classification than that of the standard statistical procedure
      (3.8% error against 18.1% with the classic method). The evolution of the
      prediction index with time for the first 12 h was different for the successfully
      and non-successfully thrombolysed groups. Specifically, in the successful
      thrombolysis group, oscillations and variation with time were more obvious,
      indicating a possible difference in the dynamics of the cardiac system.

PMID- 14686586
TI  - Three-dimensional pseudospectral modelling of cardiac propagation in an
      inhomogeneous anisotropic tissue.
AB  - Various investigators have used the monodomain model to study cardiac propagation
      behaviour. In many cases, the governing non-linear parabolic equation is solved
      using the finite-difference method. An adequate discretisation of cardiac tissue
      with realistic dimensions, however, often leads to a large model size that is
      computationally demanding. Recently, it has been demonstrated, for a two
      dimensional homogeneous monodomain, that the Chebyshev pseudospectral method can
      offer higher computational efficiency than the finite-difference technique. Here,
      an extension of the pseudospectral approach to a three-dimensional inhomogeneous
      case with fibre rotation is presented. The unknown transmembrane potential is
      expanded in terms of Chebyshev polynomial trial functions, and the monodomain
      equation is enforced at the Gauss-Lobatto node points. The forward Euler
      technique is used to advance the solution in time. Numerical results are
      presented that demonstrate that the Chebyshev pseudospectral method offered an
      even larger improvement in computational performance over the finite-difference
      method in the three-dimensional case. Specifically, the pseudospectral method
      allowed the number of nodes to be reduced by approximately 85 times, while the
      same solution accuracy was maintained. Depending on the model size, simulations
      were performed with approximately 18-41 times less memory and approximately 99
      169 times less CPU time.

PMID- 14686587
TI  - Detection of autonomic modulation in permanent atrial fibrillation.
AB  - A new signal processing method for the detection of cyclic variations in atrial
      fibrillation frequency is presented. The objective was to investigate whether or
      not respiration, through the autonomic nervous system, modulates the fibrillation
      frequency in patients with permanent atrial fibrillation. A group of eight
      patients with permanent atrial fibrillation, atrioventricular block III and a
      permanent pacemaker were studied during rest, rhythm-controlled respiration, with
      each breath lasting for 8 s (i.e. a breathing frequency of 0.125 Hz), and rhythm
      controlled respiration after full vagal blockade by atropine. Using the new
      method, a spectral peak could be detected, in two of the patients, at the
      breathing frequency during rhythm-controlled respiration then disappeared after
      injection of atropine.

PMID- 14686588
TI  - Ring electrode for radio-frequency heating of the cornea: modelling and in vitro
      experiments.
AB  - Radio-frequency thermokeratoplasty (RF-TKP) is a technique used to reshape the
      cornea curvature by means of thermal lesions using radio-frequency currents. This
      curvature change allows refractive disorders such as hyperopia to be corrected. A
      new electrode with ring geometry is proposed for RF-TKP. It was designed to
      create a single thermal lesion with a full-circle shape. Finite element models
      were developed, and the temperature distributions in the cornea were analysed for
      different ring electrode characteristics. The computer results indicated that the
      maximum temperature in the cornea was located in the vicinity of the ring
      electrode outer perimeter, and that the lesions had a semi-torus shape. The
      results also indicated that the electrode thickness, electrode radius and
      electrode thermal conductivity had a significant influence on the temperature
      distributions. In addition, in vitro experiments were performed on rabbit eyes.
      At 5 W power, the lesions were fully circular. Some lesions showed non-uniform
      characteristics along their circular path. Lesion depth depended on heating
      duration (60% of corneal thickness for 20 s, and 30% for 10 s). The results
      suggest that the critical shrinkage temperature (55-63 degrees C) was reached at
      the central stroma and along the entire circular path in all the cases.

PMID- 14686589
TI  - Frequency dependence of the cardiac threshold to alternating current between 10
      Hz and 160 Hz.
AB  - It is still unclear what fundamental criteria influence the ability of
      alternating current (AC) to induce ventricular fibrillation (VF) in vivo. As the
      VF threshold has a bowl-shaped relationship with frequency (showing a minimum
      threshold at some frequency), similar to the nervous system, one proposed model
      has assumed that the mechanisms underlying AC stimulation of nerves are at work
      for VF induction. More recent work has suggested a second approach, whereby a
      simple RC-like model is sufficient to understand the cardiac AC stimulation
      threshold's frequency dependence, suggesting that some unarticulated mechanism is
      at work for VF. The paper directly tests these two models. In 12 intact dogs and
      20 intact guinea pigs, DC pulses were used to stimulate AC square and AC sine
      waves at 10, 20, 40, 80 and 160 Hz. All electrodes were endocardial, with the
      return electrode being on a paw or thorax. It was found that, for square and sine
      wave stimulation in both dogs and guinea pigs, the stimulation threshold
      increased monotonically with frequency from 10 Hz up to 160 Hz (p < 0.01 for dogs
      and guinea pigs). Between 80 and 160 Hz, the AC stimulation threshold doubled,
      exactly as predicted by an RC model. It was concluded that the AC stimulation
      threshold is not bowl-shaped and is best understood with an RC model. As the VF
      threshold does exhibit a bowl-shape with frequency, as opposed to the stimulation
      threshold which does not, the VF induction frequency dependence must have
      different origins.

PMID- 14686590
TI  - Automatic identification of motor unit action potential trains from
      electromyographic signals using fuzzy techniques.
AB  - A technique is proposed that allows automatic decomposition of electromyographic
      (EMG) signals into their constituent motor unit action potential trains (MUAPTs).
      A specific iterative algorithm with a classification method using fuzzy-logic
      techniques was developed. The proposed classification method takes into account
      imprecise information, such as waveform instability and irregular firing
      patterns, that is often encountered in EMG signals. Classification features were
      determined by the combining of time position and waveform information.
      Statistical analysis of inter-pulse intervals and spike amplitude provided an
      accurate estimation of features used in the classification step. Algorithm
      performance was evaluated using simulated EMG signals composed of up to six
      different discharging motor units corrupted with white noise. The algorithm was
      then applied to real signals recorded by a high spatial resolution surface EMG
      device based on a Laplacian spatial filter. On six groups of 20 simulated
      signals, the decomposition algorithm performed with a maximum and an average mean
      error rate of 2.13% and 1.37%, respectively. On real surface EMG signals recorded
      at different force levels (from 10% to 40% of the maximum voluntary contraction),
      the algorithm correctly identified 21 MUAPTs, compared with the 29 MUAPTs
      identified by an experienced neurophysiologist. The efficiency of the
      decomposition on surface EMG signals makes this method very attractive for non
      invasive investigation of physiological muscle properties. However, it can also
      be used to decompose intramuscularly recorded EMG signals.

PMID- 14686591
TI  - Implantable telemeter for long-term electroneurographic recordings in animals and
      humans.
AB  - A system is described that amplifies an electroneurographic signal (ENG) from a
      tripolar electrode nerve cuff and transmits it from the implanted amplifier to an
      external drive box. The output was raw ENG, bandpass filtered from 800 to 8000
      Hz. The implant was powered by radio-frequency induction and operated for coil-to
      coil separations up to 30 mm. The testing and performance of the system is
      described. The input-referred noise was never more than 1 microV RMS, and, at
      some positions of the radio-frequency field, was 0.7 microV, close to the
      expected value for the amplifier used. The common-mode rejection ratio (CMRR)
      depended on the impedance imbalance from the cuff and the length of input cable.
      Devices with a short cable and low source impedance had CMRR of 84 dB, but, with
      31 cm of cable and a real cuff, the CMRR fell to 66 dB. Recovery from a stimulus
      artifact took 5 ms. The responses of the cuff to external potential gradients and
      to common-mode signals are described theoretically or by simulation. The devices
      are available for use in neuroprosthetic or neurophysiological research.

PMID- 14686593
TI  - Enhancement of electrolarynx speech using adaptive noise cancelling based on
      independent component analysis.
AB  - The electrolarynx provides a valuable means of verbal communication for people
      who cannot use their natural voice-production mechanism, but technology has
      changed very little since it was introduced in the 1950s. The presence of
      background noise degrades the resulting speech. In this study background noise
      was reduced by a new method, independent component analysis-based adaptive noise
      cancelling, which can remove noise components of the primary input signal based
      on statistical independence, by incorporating both second-order and higher-order
      statistics. The method shows better performance than the conventional least mean
      square algorithm. Acoustic analysis of the denoised electrolarynx speech revealed
      a significant reduction in the amount of background noise. Results from the
      perceptual evaluations indicated that the new filtering technique produced a
      noticeable improvement in the acceptability of the electrolarynx speech in a
      quiet environment (from 1.75 to 2.49, arbitrary units) or a noisy environment
      (from 0.59 to 1.82). In general, there was no significant improvement or
      degradation in intelligibility in the quiet environment (from 52.7 to 53.3).
      However, the processing did improve the intelligibility in a babble-noise
      environment (from 24.9 to 40.6). The improvement in acceptability and
      intelligibility may increase the communication ability of the user in daily
      situations.

PMID- 14686592
TI  - Surface electromyography and mechanomyography recording: a new differential
      composite probe.
AB  - The objective of the study was to develop a new surface probe for differential
      mechanomyographic (MMG) and electromyographic (EMG) recording. Differential
      amplification is commonly used in electromyography to improve the signal-to-noise
      ratio. A new composite probe was developed with two electrodes (EMG) and two
      identical piezo-electric membranes (MMG) to be positioned on muscle. The probe
      had two built-in fixed-gain differential amplifiers: one to amplify the electric
      signal and the other to amplify the vibration signal. A similar non-differential
      MMG probe was used for comparisons. Burst muscular activity was recorded using
      the non-differential and differential probes and was used to test the performance
      of the two probes in suppressing artifacts of non-muscular origin. Power spectrum
      analysis of signals from the two probes showed that differential amplification
      significantly improved the signal-to-noise ratio in MMG recordings and
      significantly suppressed artifacts (power difference > 90%). The composite probe
      allowed simultaneous differential recording of MMG and EMG signals from the same
      muscular site. It recorded muscular activity more efficiently than the non
      differential probe and could therefore be useful in studying fatigue and
      neuromuscular diseases.

PMID- 14686594
TI  - Evaluation of methods for opto-electronic body surface sensing applied to patient
      position control in breast radiation therapy.
AB  - The accuracy gap between the high levels of accuracy in radiotherapy planning and
      the uncertain set-up of each therapy fraction represents a crucial factor in the
      optimisation of radiation treatment. This occurs because the conventional means
      of patient alignment and immobilisation do not guarantee accurate implementation
      of the therapy plan in the actual irradiation treatment. A patient repositioning
      technique is proposed, based on opto-electronic motion capture and on methods of
      registration of body surfaces described by a limited dataset. The validation of
      the method was related to breast cancer radiotherapy and was based on simulated
      and experimental repositioning procedures involving a phantom and two subjects.
      With respect to previous work, the surface registration procedure was, in this
      case, implemented as a constrained non-linear least-square problem (constraints
      were given by the position of a couple of passive markers placed on the sternum),
      and three different algorithms were compared in terms of accuracy in misalignment
      detection and of computational cost. The simulation and experimental activities
      identified the best performing algorithm, which systematically limited the
      repositioning errors to below clinically acceptable thresholds (5 mm), with
      residual surface mismatches lower than 2 mm.

PMID- 14686595
TI  - Analytical guide wire motion algorithm for simulation of endovascular
      interventions.
AB  - Performing minimally invasive vascular interventions requires proper training, as
      a guide wire needs to be manipulated, by the tail, under fluoroscopic guidance.
      To provide a training environment, the motion of the guide wire inside the human
      vasculature can be simulated by computer. Such a simulation needs to be based on
      an algorithm that is both realistic and fast. To meet these two demands, an
      analytical solution to the problem of guide wire motion has been derived, using a
      new parametrisation of guide wire shape. The algorithm is highly generic, is
      entirely based on elementary physics and has good convergence properties
      (accuracy of 22 micron after two iterations). In an experimental validation of
      the algorithm in a planar model, the RMS of the spatial discrepancy between the
      real and simulated catheter positions was about 10% of the lumen size. Comparison
      of the simulated guide wire motion with 3D rotational angiography data of a real
      guide wire advanced in a plastic phantom of the cerebral vasculature showed that
      the new algorithm produced realistic results.

PMID- 14686596
TI  - Modified implanted drop foot stimulator system with graphical user interface for
      customised stimulation pulse-width profiles.
AB  - A modified implanted drop foot stimulator that allows cyclic modulation of the
      stimulation pulse-width during gait has been developed. Stimulation was on two
      channels of a four-channel 12 polar cuff electrode. The stimulator allowed
      modulation of stimulation pulse-width, between 0 and 255 micros, on both channels
      throughout the swing and stance phases of gait. Stimulation was applied between
      17 and 40 Hz. The clinician can specify an infinite range of stimulation profiles
      on a desktop computer, using a user-friendly LabVIEW interface. The desktop
      program generated a stimulation profile table of 100 values, which was then
      downloaded to the drop foot stimulator. As each phase of gait imposed different
      biomechanical demands on the ankle dorsiflexor muscles, different stimulation
      intensities were desirable, throughout gait, to match these demands. Moreover, as
      the gait of each person with hemiplegia is unique, the biomechanical demands
      imposed throughout the gait cycle for each user of a drop foot stimulator are
      unique. This stimulator architecture allowed the clinician to, specify
      stimulation intensities individually, at each phase of the gait cycle for each
      drop foot stimulator user. The stimulator was evaluated on a male hemiplegic
      subject. It was used to increase the stimulation pulse-width by 150% at 5% of
      gait cycle prior to heel strike. The system performed well, with the ankle angle
      at heel strike increasing by 5 degrees owing to this increased pulse-width.

PMID- 14686597
TI  - Command control for functional electrical stimulation hand grasp systems using
      miniature accelerometers and gyroscopes.
AB  - Recent commercially available miniature sensors have the potential to improve the
      functions of functional electrical stimulation (FES) systems in terms of control,
      reliability and robustness. A new control approach using a miniature gyroscope
      and an accelerometer was studied. These sensors were used to detect the linear
      acceleration and angular velocity of residual voluntary movements on upper limbs
      and were small and easy to put on. Five healthy subjects and three cervical
      spinal cord injured subjects were recruited to evaluate this controller. Sensors
      were placed on four locations: the shoulder, upper arm, wrist and hand. A quick
      forward-and-backward movement was employed to produce a distinctive waveform that
      was different from general movements. A detection algorithm was developed to
      generate a command signal by identifying this distinctive waveform through the
      detection of peaks and valleys in the sensor's signals. This command signal was
      used to control different FES hand grasp patterns. With a specificity of 0.9, the
      sensors had a success rate of 85-100% on healthy subjects and 82-97% on spinal
      cord injured subjects. In terms of sensor placement, the gyroscope was better as
      a control source than the accelerometer for wrist and hand positions, but the
      reverse was true for the shoulder.

PMID- 14686598
TI  - Power requirements for vibrotactile piezo-electric and electromechanical
      transducers.
AB  - Human-machine information transfer through tactile excitation has addressed new
      applications in virtual reality, robotics, telesurgery, sensory substitution and
      rehabilitation for the handicapped in the past few years. Power consumption is an
      important factor in the design of vibrotactile displays, because it affects
      energy needs and the size, weight, heat dissipation and cost of the associated
      electronics. An experimental study is presented on the power required to reach
      tactile thresholds in electromechanical and piezo-electric transducers. Three
      different waveforms are considered, with an excitatory period formed by a burst
      of rectangular 50% duty cycle pulses (R50), rectangular low duty cycle pulses
      (RLO) and sinusoidal pulses (SIN). Ten different pulse repetition periods (RPs)
      were considered in the range 1/550-1/25 s. The voltage and current waveforms
      applied to the transducers at sensation thresholds in a group of 12 healthy
      subjects were sampled and stored in a digital oscilloscope. The average power was
      determined for each subject, and differences of two orders of magnitude were
      measured between the electromechanical and the piezo-electric transducer power
      consumption. Results show that, for the electromechanical transducer, a smaller
      power consumption of 25 microW was determined for RP = 1/25 s and the RLO
      waveform. In the case of the piezo-electric transducer, power of 0.21 microW was
      determined for SIN excitation and RP = 1/250 s. These results show the advantages
      of reducing power requirements for vibrotactile displays, which can be optimised
      by the choice of appropriate types of transducer, excitatory waveforms and pulse
      repetition periods.

PMID- 14686599
TI  - Automatic analysis of electro-encephalogram sleep spindle frequency throughout
      the night.
AB  - A fully automatic method to analyse electro-encephalogram (EEG) sleep spindle
      frequency evolution during the night was developed and tested. Twenty all-night
      recordings were studied from ten healthy control subjects and ten sleep apnoea
      patients. A total of 22,868 spindles were detected. The overall mean spindle
      frequency was significantly higher in the control subjects than in the apnoea
      patients (12.5 Hz against 11.7 Hz, respectively; p<0.004). The proposed method
      further identified the sleep depth cycles, and the mean spindle frequency was
      automatically determined inside each sleep depth cycle. In control subjects, the
      mean spindle frequency increased from 12.0 Hz in the first sleep depth cycle to
      12.6 Hz in the fifth cycle. No such increase was observed in the sleep apnoea
      patients. This difference in the spindle frequency evolution was statistically
      significant (p<0.004). The advantage of the method is that no EEG amplitude
      thresholds are needed.

PMID- 14686600
TI  - Mechanisms governing the visco-elastic responses of living cells assessed by foam
      and tensegrity models.
AB  - The visco-elastic properties of living cells, measured to date by various
      authors, vary considerably, depending on the experimental methods and/or on the
      theoretical models used. In the present study, two mechanisms thought to be
      involved in cellular visco-elastic responses were analysed, based on the idea
      that the cytoskeleton plays a fundamental role in cellular mechanical responses.
      For this purpose, the predictions of an open unit-cell model and a 30-element
      visco-elastic tensegrity model were tested, taking into consideration similar
      properties of the constitutive F-actin. The quantitative predictions of the time
      constant and viscosity modulus obtained by both models were compared with
      previously published experimental data obtained from living cells. The small
      viscosity modulus values (10(0)-10(3) Pa x s) predicted by the tensegrity model
      may reflect the combined contributions of the spatially rearranged constitutive
      filaments and the internal tension to the overall cytoskeleton response to
      external loading. In contrast, the high viscosity modulus values (10(3)-10(5) Pa
      x s) predicted by the unit-cell model may rather reflect the mechanical response
      of the cytoskeleton to the bending of the constitutive filaments and/or to the
      deformation of internal components. The present results suggest the existence of
      a close link between the overall visco-elastic response of micromanipulated cells
      and the underlying architecture.

PMID- 14686601
TI  - Synthesis and evaluation of amphiphilic RGD derivatives: uses for solvent casting
      in polymers and tissue engineering applications.
AB  - Derivatives containing arginine-glycine-aspartic acid (RGD) inhibit fibrinogen
      binding to activated platelets and promote endothelial and smooth muscle cell
      attachment. An amphiphilic derivative of RGD that can be dissolved in an organic
      solvent has potential in the development of non-thrombogenic biomaterials. Such a
      derivative, LA-GRGD, was synthesised by coupling glycine-arginine-glycine
      aspartic acid (GRGD) with lauric acid (LA). Its solubility and antithrombotic,
      cytotoxic and cell-binding effects were then evaluated in comparison with heparin
      (which is used clinically) and a fibronectin-engineered protein polymer (FEPP).
      Thromboelastography (TEG) was used to measure blood clotting time using fresh
      whole blood from healthy volunteers. Tissue factor (TF) activity was measured
      using plasma with a standard prothrombin time assay (PT). Cytotoxicity was
      assessed on human umbilical cord endothelial cells (HUVECs) using an Alamar blue
      assay. Solubility of the conjugate was assessed in a co-solvent. These techniques
      were used to study LA-GRGD, using heparin and FEPP as controls. The amphiphilic
      property of LA-GRGD was dependent on the feed mole ratio of GRGD to LA. LA-GRGD
      was soluble in acetone:water and water. LA-GRGD inhibited TF by >90% and
      prolonged TEG-r by 8.2+/-3.3 min (200 microg ml(-1)). Heparin inhibited TF by
      >90%, but prolonged TEG-r by 97.4+/-1.6 min (1 U ml(-1)); FEPP inhibited TF by
      >90% (100 microg ml(-1)) and prolonged TEG-r by 73.7+/-8.4 min (10 microg ml(
      1)). Heparin had no cytotoxic effect on EC metabolism and viability at the
      concentrations studied (0.1-100 U ml(-1)). No significant cytotoxic effect was
      produced by LA-GRGD or FEPP at concentrations ranging from 0.1 microg ml(-1) to
      50 microg ml(-1), but, at higher concentrations (100 microg ml(-1) and 200 microg
      ml(-1)), a detrimental effect was observed. Cell binding studies showed that LA
      GRGD bound 29% of ECs compared with FEPP (60%) and heparin (22%). This new
      approach for synthesising amphiphilic RGD and its analogues has potential as a
      drug delivery system for the manufacture of new polymer formulations for use in
      bypass grafts and other tissue-engineered devices.

PMID- 14686602
TI  - A mariner-like element with a 5' lesion in Drosophila simulans.
AB  - The unstable white-S2 (wS2) allele of the white gene occurred spontaneously in
      the S2 strain of Drosophila simulans. This mutation was caused by insertion of
      the submariner element, a mariner-like element with an abnormal tandem
      duplication of the 5' inverted terminal repeat (ITR). Although it has an
      incomplete ITR, submariner excises efficiently. The rate of somatic reversion,
      estimated by the number of eye-color mosaic flies, was 79.9%, and the reversion
      frequency in the germline was 0.6%. The change to the 5' ITR contributes to make
      this transposon precise excision.

PMID- 14686603
TI  - Effects of short-term spontaneous mutation accumulation for life history traits
      in grape phylloxera, Daktulosphaira vitifoliae.
AB  - Mutation is the source of all genetic variation, but rate of input and effects of
      new mutations for phenotypic traits related to fitness and the role they play in
      the maintenance of genetic variation are still subject to controversy. These
      parameters are important in models of the evolution of sex and recombination, the
      persistence of asexual populations, and the extinction of small populations. Most
      estimates have come from a few model organisms. Here, mutation accumulation
      experiments were conducted with three clones of grape phylloxera, Daktulosphaira
      vitifoliae Fitch, a gall forming herbivore and pest of grapes, to estimate the
      rate of input and effects of spontaneous mutation on life history traits. This is
      perhaps the first such experiment using a non-model organism of economic
      importance. Significant heritable genetic variation accrued in one of three sets
      of lines for one of four traits measured, and deleterious effects of mutation
      were found for two of four traits in two of the three sets of lines. Estimates of
      the parameters by the Bateman-Mukai (BM) method were within the range found in
      previous studies but at the lower end for genomic mutation rate, U approximately
      0.023 and mutational variance, V(M) approximately 0.0003, the upper end for
      average heterozygous effect, alpha, of approximately -0.11, and on the order of
      previous estimates for mutational heritability, hM approximately 0.007. Under a
      model of equal effects of mutations, maximum likelihood (ML) estimates of U were
      slightly higher, and of alpha lower, than the BM estimates. Support limits were
      too large to provide much confidence in the ML estimates, however, and models of
      mutational effects assuming a gamma distribution of effects under different
      values of the shape parameter, beta, could not be distinguished though
      likelihoods tended to be lower at lower values of beta (more leptokurtic). Rapid
      accumulation of deleterious mutations suggest that for many pest species,
      adaptive response under agricultural conditions may depend more on the standing
      variation derived from introductions than new mutation.

PMID- 14686604
TI  - Replication banding in two Mediterranean moray eels: chromosomal characterization
      and comparison.
AB  - Early and late replication bandings have been obtained by in vitro BrdU
      incorporation in the Mediterranean Muraenidae species Muraena helena and
      Gymnothorax unicolor, and used to characterize their karyotypes. A comparative
      analysis of the banding patterns allowed to point out high karyotype similarity
      as well as chromosome rearrangements that occurred in karyotype evolution between
      these species.

PMID- 14686605
TI  - Predictive validity of discriminant analysis for genetic data.
AB  - We examined the predictive validity of the results using discriminant analysis to
      distinguish statistically among two or more populations with a large sample of
      random amplified polymorphic DNA (RAPD) loci, but a small sample of genotypes
      from each population. We compared and contrasted results from randomized data
      with results from real data of three studies by 100 randomized shuffling of
      genotypes into various populations. We generally obtained substantial differences
      between results from randomized data compared to those from the real data in
      several characteristics of discriminant analysis. We showed that a high level of
      correctly classified percentage is also obtainable in the analysis of randomized
      data, mainly with a low number of populations. However, the correctly classified
      percentage obtained from the real data was generally significantly higher than
      the percentage obtained from the randomized data. We suggested that the high
      level of real differences in allele frequencies of the RAPD polymorphic loci
      clearly distinguished the various populations and that the populations differ
      significantly in their RAPD contents in accordance with ecological heterogeneity.
      We obtained either no or a low level of difference between the correct
      classification rate obtained by the leaving-one-out procedure and that obtained
      from the original data, attributed to a low number of loci selected by the
      stepwise method. The results strengthen and support our conclusion and lead us to
      focus on the discriminant analysis by selecting only low numbers of
      discriminating variables.

PMID- 14686606
TI  - Tests for a disease-susceptibility locus allowing for an inbreeding coefficient
      (F).
AB  - We begin by discussing the false positive test results that arise because of
      cryptic relatedness and population substructure when testing a disease
      susceptibility locus. We extend and evaluate the Hardy-Weinberg disequilibrium
      (HWD) method, allowing for an inbreeding coefficient (F) in a similar way that
      Devlin and Roeder (1999) allowed for inbreeding in a case-control study. Then we
      compare the HWD measure and the common direct measure of linkage disequilibrium,
      both when there is no population substructure (F = 0) and when there is
      population substructure (F not = 0), for a single marker. The HWD test statistic
      gives rise to false positives caused by population stratification. These false
      positives can be controlled by adjusting the test statistic for the amount of
      variance inflation caused by the inbreeding coefficient (F). The power loss for
      the HWD test that arises when controlling for population structure is much less
      than that which arises for the common direct measure of linkage disequilibrium.
      However, in the multiplicative model, the HWD test has virtually no power even
      when allowing for non-zero F.

PMID- 14686607
TI  - The effects of selection for early (day) and late (dusk) mating lines of hybrids
      of Bactrocera tryoni and Bactrocera neohumeralis.
AB  - Bactrocera neohumeralis and Bactrocera tryoni are closely related tephritid fruit
      fly species. B. neohumeralis mates throughout the day (in bright light) and B.
      tryoni mates at dusk. The two species can also be distinguished by the colour of
      their calli (prothoracic sclerites) which are brown and yellow, respectively. The
      F1 hybrids can mate both in bright light just before dusk and during dusk and
      have calli that are partly brown and partly yellow. The F2 hybrids have a wider
      range of callus patterns and mating occurs more widely in the day as well as at
      dusk. We directly selected hybrid stocks for mating time, creating 'early' (day
      mating) and 'late' (dusk-mating) lines. As an apparently inadvertent consequence,
      the two types of line respectively had predominantly brown and predominantly
      yellow calli and thus came to closely resemble the original two species in both
      behaviour and appearance. Lines that were evenly selected (half for day and half
      for dusk) essentially retained the mating pattern of F2 hybrids. Selection for
      callus colour alone also affected the distribution of mating times in a
      predictable way. We propose a genetical model to account for the results and
      discuss them in the light of the apparent maintenance of species integrity in
      nature.

PMID- 14686608
TI  - Assortative mating and fertility in two Drosophila subobscura strains with
      different mitochondrial DNA haplotypes.
AB  - The mating pattern and female fertility on the two main mitochondrial DNA
      haplotypes (I and II) of Drosophila subobscura were studied, in an attempt to
      find possible differences between them in relation to sexual selection or
      isolation that could explain the populational dynamics and the co-existence of
      these two strains in nature. The mating pattern indicated an assortative mating
      in population cages, where couples of the same haplotype, mainly those of
      haplotype I, mated more often. However, the significations detected in laboratory
      conditions disappeared in wild populations, where random mating was the rule. The
      female fertility also showed differences in the laboratory compared to the wild,
      since couples with haplotype I males were more efficient in the laboratory
      populations. These results, together with others that we previously obtained,
      either point to selection acting directly on the mtDNA or to the presence of some
      kind of cytonuclear co-adaptation in these two haplotypes, although this must be
      modulated by other factors that change with the seasons and time. The end result
      could well be a balance of opposite forces acting on both haplotypes.

PMID- 14686609
TI  - LOD score exclusion analyses for candidate QTLs using random population samples.
AB  - While extensive analyses have been conducted to test for, no formal analyses have
      been conducted to test against, the importance of candidate genes as putative
      QTLs using random population samples. Previously, we developed an LOD score
      exclusion mapping approach for candidate genes for complex diseases. Here, we
      extend this LOD score approach for exclusion analyses of candidate genes for
      quantitative traits. Under this approach, specific genetic effects (as reflected
      by heritability) and inheritance models at candidate QTLs can be analyzed and if
      an LOD score is < or = -2.0, the locus can be excluded from having a heritability
      larger than that specified. Simulations show that this approach has high power to
      exclude a candidate gene from having moderate genetic effects if it is not a QTL
      and is robust to population admixture. Our exclusion analysis complements
      association analysis for candidate genes as putative QTLs in random population
      samples. The approach is applied to test the importance of Vitamin D receptor
      (VDR) gene as a potential QTL underlying the variation of bone mass, an important
      determinant of osteoporosis.

PMID- 14686610
TI  - New embryo lethals in Arabidopsis thaliana: basic genetic and morphological
      study.
AB  - Six different mutations with defects in immature seed development have been
      identified during screening of a T-DNA collection of Arabidopsis thaliana. The
      mutations were confirmed to be monogenic and recessive-lethal by genetic
      analysis. Mutant embryos were blocked in certain steps in the process necessary
      for embryo viability and development, and therefore they belong to the embryo
      lethal class of mutants. The genetic and morphological studies of T-DNA mutations
      affecting embryo development are presented. The youngest embryos with a defect
      were observed at the globular stage in the VIII-64 mutation. Externally located
      cells, precursor of the protoderm, were characterised by abnormal cell division.
      VIII-41 mutation with a defect at the late globular stage was arrested at the
      globular-heart stage transition. VIII-111 mutation showed defect at heart stage
      of embryogenesis with atypical development of cotyledon primordia. The defect was
      associated with abnormal pattern of cell division constituting the precursor of
      the shoot apical meristem. In VIII-82 mutation defect in torpedo stage with
      asymmetric cotyledons was observed. Cotyledon stage of embryos and chlorophyll
      defect were observed in VIII-75 mutant. Abnormal suspensor consisting of two
      columns of cells was observed in 280-4-4 mutation. Newly identified embryo
      lethals can serve as starting material for more detailed genetic and molecular
      studies.

PMID- 14686611
TI  - The origin of the achiasmatic XY sex chromosome system in Cacopsylla peregrina
      (Frst.) (Psylloidea, Homoptera).
AB  - The status of an extra univalent, if it is a B chromosome or an achiasmatic Y
      chromosome, associating with the X chromosome in male meiosis of Cacopsylla
      peregrina (Frst.) (Homoptera, Psylloidea) was analysed. One extra univalent was
      present in all males collected from three geographically well separated
      populations, it was mitotically stable, and showed precise segregation from the X
      chromosome. These findings led us to propose that the univalent represents in
      fact a Y chromosome. The behaviour of the X and Y chromosomes during meiotic
      prophase suggested that their regular segregation was based on an achiasmatic
      segregation mechanism characterised by a 'touch and go' pairing of segregating
      chromosomes at metaphase I. To explain the formation of the achiasmatic Y within
      an insect group with X0 sex chromosome system, it was suggested that the Y
      chromosome has evolved from a mitotically stable B chromosome that was first
      integrated into an achiasmatic segregation system with the X chromosome, and has
      later become fixed in the karyotype as a Y chromosome.

PMID- 14686612
TI  - Evolution of the spindlin gene in birds: independent cessation of the
      recombination of sex chromosomes at the spindlin locus in neognathous birds and
      tinamous, a palaeognathous avian family.
AB  - Tinamous (Aves, Palaeognathae, Tinamiformes) are primitive birds, generally
      considered to be the sister group to the ratites. Tinamous possess a W sex
      chromosome, intermediate in heterochromatization between the largely euchromatic
      W chromosome of the ratites and the highly condensed W chromosome of the
      neognathous birds. Of the four genes which are known to have diverged copies on
      the neognathous avian W and Z chromosome (ATP5A1, CHD1, PKC and SPIN) only the
      spindlin gene has W- and Z-chromosomal forms in the tinamiformes. This paper
      describes experiments which show that the sequences of these forms are more
      similar to each other and to the homologous undifferentiated spindlin gene
      sequences in the ratite genome than to the W or Z forms of the spindlin gene in
      other, neognathous species. This suggests that cessation of recombination at the
      spindlin locus of the ancestral W and Z chromosomes of the paleognathous
      tinamiformes and the neognathous avian species were independent events.

PMID- 14686613
TI  - Hydrogen peroxide mediates interleukin-1beta-induced AP-1 activation in articular
      chondrocytes: implications for the regulation of iNOS expression.
AB  - The pro-inflammatory cytokine interleukin-1beta (IL-1) induces articular
      chondrocytes to produce reactive oxygen species (ROS), including hydrogen
      peroxide (H2O2), which mediate some IL-1-induced responses. This study aimed at
      elucidating the role of ROS, particularly H2O2, in mediating IL-1-induced
      activation of the transcription factor activator protein-1 (AP-1) in primary
      cultures of articular chondrocytes. AP-1 may function either as an inducer or as
      a repressor of the inducible nitric oxide synthase (iNOS) gene promoter. Since we
      observed that AP-1 is not required for iNOS expression in chondrocytes, we also
      investigated whether it is a repressor of this gene. The results of
      electrophoretic mobility shift assays showed that both IL-1 and H2O2 activated AP
      1 and that inhibition of IL-1-induced ROS production abrogated AP-1 activation.
      The AP-1 complexes, induced by either IL-1 or H2O2, contained c-Fos/c-Jun and c
      Fos/JunD heterodimers, but IL-1 activated AP-1 with a kinetics slower than that
      observed with H2O2. Pre-activation of AP-1, before stimulation of the cells with
      IL-1, did not inhibit iNOS mRNA and protein synthesis, relative to cells treated
      with IL-1 alone. These results indicate that H2O2 is a major mediator of IL-1
      induced AP-1 activation in articular chondrocytes and that inhibition of ROS
      production is an effective strategy to block this IL-1-induced response. This
      study also identifies c-Fos/c-Jun and c-Fos/JunD heterodimers as the AP-1
      transcription factors induced by IL-1, which, although not involved in the
      transcriptional regulation of the iNOS gene, may be important for the regulation
      of other genes also relevant in arthritic diseases, namely the collagenase-1 and
      IL-8 genes.

PMID- 14686614
TI  - Teratogen-induced activation of caspase-6 and caspase-7 in early postimplantation
      mouse embryos.
AB  - BACKGROUND: Previous work has shown that teratogens such as hyperthermia (HS), 4
      hydroperoxycyclophosphamide (4CP), and staurosporine (ST) induce cell death in
      day 9 mouse embryos by activating the mitochondrial apoptotic pathway. Key to the
      activation of this pathway is the activation of a caspase cascade involving the
      cleavage-induced activation of an initiator procaspase, caspase-9, and the
      downstream effector procaspase, caspase-3. For example, procaspase-3, an inactive
      proenzyme of 32 kDa is cleaved by activated caspase-9 to generate a large subunit
      of approximately 17 kDa and a small subunit of approximately 10 kDa. In turn,
      caspase-3 is known to target a variety of cellular proteins for proteolytic
      cleavage as part of the process by which dying cells are eliminated. Previous
      work has also shown that neuroepithelial cells are sensitive to teratogen-induced
      activation of this pathway and subsequent cell death whereas cells of the heart
      are resistant. Although caspase-3 is a key effector caspase activated by
      teratogens, two other effector caspases, caspase-6 and caspase-7, are known;
      however, their role in teratogen-induced cell death is unknown. METHODS: Because
      cleavage-induced generation of specific subunits is the most specific assay for
      activation of caspases, we have used antibodies that recognize the procaspase and
      one of its active subunits and a Western blot approach to assess the activation
      of caspase-6 and caspase-7 in day 9 mouse embryos (or heads, hearts and trunks
      isolated from whole embryos) exposed to HS, 4CP, and ST. To probe the
      relationship between teratogen-induced activation of caspase-9/caspase-3 and the
      activation of caspase-6/caspase-7, we used a mitochondrial-free embryo lysate
      with or without the addition of cytochrome c, recombinant active caspase-3, or
      recombinant active caspase-9. RESULTS: Western blot analyses show that these
      three teratogens, HS, 4CP, and ST, induce the activation of procaspase-6
      (appearance of the 13 kDa subunit, p13) and caspase-7 (appearance of the 19 kDa
      subunit, p19) in day 9 mouse embryos. In vitro studies showed that both caspase-6
      and caspase-7 could be activated by the addition of cytochrome c to a lysate
      prepared from untreated embryos. In addition, caspase-6 could be activated by the
      addition of either recombinant caspase-3 or caspase-9 to a lysate prepared from
      untreated embryos. In contrast, caspase-7 could be activated by addition of
      recombinant caspase-3 but only minimally by recombinant caspase-9. Like caspase
      9/caspase-3, caspase-6 and caspase-7 were not activated in hearts isolated from
      embryos exposed to these three teratogens. CONCLUSIONS: HS, 4CP and ST induce the
      cleavage-dependent activation of caspase-6 and caspase-7 in day 9 mouse embryos.
      Results using DEVD-CHO, a caspase-3 inhibitor, suggest that teratogen-induced
      activation of caspase-6 is mediated by caspase-3. In addition, our data suggest
      that caspase-7 is activated primarily by caspase-3; however, we cannot rule out
      the possibility that this caspase is also activated by caspase-9. Finally, we
      also show that teratogen-induced activation of caspase-6 and caspase-7 are
      blocked in the heart, a tissue resistant to teratogen-induced cell death.

PMID- 14686615
TI  - Rotating wall vessel as a new in vitro shear stress generation system:
      application to rat coronary endothelial cell cultures.
AB  - In this paper, we describe a simple new design for the application of controlled,
      top-hat profiled wall shear stress forces in a way that is independent of
      hydrostatic pressure and oxygen tension, based on a rotating wall vessel system.
      This system has been applied to the culture of rat coronary endothelial cells
      obtained with a Langendorff-derived procedure isolation. Endothelial cells are
      immunopurified on the basis of RECA expression, and conservation of endothelial
      phenotype has been assessed on the basis of morphology, RECA and von Willebrand
      factor expressions and diI-Ac-LDL uptake. Shear stress induced by the rotating
      wall vessel was measured using a mathematical formula specifically designed for
      this type of model, and its impact on coronary endothelial cells was evaluated.
      Shear stress produced cell orientation parallel to the flux direction, elevated
      NO production and decreased monocyte adhesion. Cells were kept viable and
      functional for at least 4 days under shear. This simple design allows the
      handling and management of numerous vials in parallel and appears to be suitable
      for large-scale studies of both the acute and chronic impact of modulation of the
      physico-chemical environment on endothelial cell physiology and function.

PMID- 14686616
TI  - Cyanidin and cyanidin 3-O-beta-D -glucoside as DNA cleavage protectors and
      antioxidants.
AB  - Anthocyanins, colored flavonoids, are water-soluble pigments present in the plant
      kingdom; in fact they are secondary plant metabolites responsible for the blue,
      purple, and red color of many plant tissues. Present in beans, fruits, vegetables
      and red wines, considerable amounts of anthocyanins are ingested as constituents
      of the human diet (180-215 mg daily). There is now increasing interest in the in
      vivo protective function of natural antioxidants contained in dietary plants
      against oxidative damage caused by free radical species. Recently, the
      antioxidant activity of phenolic phytochemicals, has been investigated. Since the
      antioxidant mechanism of anthocyanin pigments is still controversial, in the
      present study we evaluated the effects of cyanidin and cyanidin 3-O-beta-D
      glucoside on DNA cleavage, on their free radical scavenging capacity and on
      xanthine oxidase activity. Cyanidin and cyanidin 3-O-beta-D-glucoside showed a
      protective effect on DNA cleavage, a dose-dependent free radical scavenging
      activity and significant inhibition of XO activity. These effects suggest that
      anthocyanins exhibit interesting antioxidant properties, and could therefore
      represent a promising class of compounds useful in the treatment of pathologies
      where free radical production plays a key role.

PMID- 14686618
TI  - The Disaster Reserve Partner Group at NYCOM.

PMID- 14686617
TI  - Toxicity and metabolism of subcytotoxic inorganic arsenic in human renal proximal
      tubule epithelial cells (HK-2).
AB  - Arsenic is an environmental toxicant and a human carcinogen. The kidney, a known
      target organ of arsenic toxicity, is critical for both in vivo arsenic
      biotransformation and elimination. This study investigates the potential of an
      immortalized human proximal tubular epithelial cell line, HK-2, to serve as a
      representative model for low level exposures of the human kidney to arsenic.
      Subcytotoxic concentrations of arsenite (< or = 10 micromol/L) and arsenate (<
      100 micromol/L) were determined by leakage of LDH from cells exposed for 24 h.
      Threshold concentrations of arsenite (between 1 and 10 micromol/L) and arsenate
      (between 10 and 25 micromol/L) were found to affect MTT processing by
      mitochondria. Biotransformation of subcytotoxic arsenite or arsenate was
      determined using HPLC-ICP-MS to detect metabolites in cell culture media and cell
      lysates. Following 24 h, analysis of media revealed that arsenite was minimally
      oxidized to arsenate and arsenate was reduced to arsenite. Only arsenite was
      detected in cell lysates. Pentavalent methylated arsenicals were not detected in
      media or lysates following exposure to either inorganic arsenical. The activities
      of key arsenic biotransformation enzymes--MMAV reductase and AsIII
      methyltransferase--were evaluated to determine whether HK-2 cells could reduce
      and methylate arsenicals. When compared to the activities of these enzymes in
      other animal tissues, the specific activities of HK-2 cells were indicative of a
      robust capacity to metabolize arsenic. It appears this human renal cell line is
      capable of biotransforming inorganic arsenic compounds, primarily reducing
      arsenate to arsenite. In addition, even at low concentrations, the mitochondria
      are a primary target for toxicity.

PMID- 14686619
TI  - Undergraduate osteopathic medical education.

PMID- 14686620
TI  - Osteopathic graduate medical education.

PMID- 14686621
TI  - Certification of osteopathic physicians.

PMID- 14686622
TI  - AOA continuing medical education.

PMID- 14686623
TI  - Osteopathic postdoctoral training institutions.

PMID- 14686624
TI  - Implementation of an osteopathic manipulative medicine clinic at an allopathic
      teaching hospital: a research-based experience.
AB  - Mastery of osteopathic palpatory skills and the skilled delivery of osteopathic
      manipulative treatment is a life-long venture that demands from practitioners
      increasingly sophisticated manual skills. Specific receptors and neural networks
      within the brain allow for the gradual development of refined manual skills that
      parallel responsive alterations and refinements that develop with repeated
      experience. During clinical training, most graduates of colleges of osteopathic
      medicine are not given opportunities to hone their palpatory skills. This is
      unfortunate because there is an increasing public demand for the nonpharmacologic
      treatment modalities osteopathic physicians could supply. At Berkshire Medical
      Center in Pittsfield, Mass, a major teaching affiliate of the University of
      Massachusetts Medical School in Worcester, the authors assembled a team of
      osteopathic and allopathic physicians to found an osteopathic manipulative
      medicine clinic. In this article, the authors share their experience in the
      creation of this research-based osteopathic medical clinic.

PMID- 14686625
TI  - Relations between academic performance by medical students and COMLEX-USA Level
      2: a multisite analysis.
AB  - The Comprehensive Osteopathic Medical Licensing Examination-USA (COMLEX-USA) is a
      national medical licensing examination for physicians earning the doctor of
      osteopathic medicine (DO) degree. Little has been published regarding the
      validity of this relatively new, high-stakes examination. The purpose of this
      study was to examine the validity of COMLEX-USA Level 2, which is given to fourth
      year osteopathic medical students and focuses on clinically relevant content.
      Nineteen osteopathic medical schools were asked to submit Level 2 scores and
      associated academic information, including predictions by deans or deans'
      representatives regarding whether each student would pass the examination. Twelve
      of the 17 schools that had students eligible to take the Level 2 examination
      provided data for 1254 (80%) of 1577 first-time test takers in March 2000. The
      overall mean score of study participants was 533.35, with a pass rate of 91.98%.
      The highest average correlation with COMLEX-USA Level 2 performance was with
      COMLEX-USA Level 1 scores (r = 0.76), followed by basic science grade point
      average (GPA) (r = .66), total GPA as a fourth-year student (r = .65), and
      clinical GPA (r = .36). Students identified as being at highest risk received the
      lowest mean score (427.54) and were most likely to fail Level 2. COMLEX-USA Level
      2 scores are moderately to highly related to academic achievement in osteopathic
      medical schools.

PMID- 14686626
TI  - Inclusion of evidence-based medicine in colleges of osteopathic medicine and
      suggestions for implementing evidence-based medicine into osteopathic medical
      school curricula.
AB  - The authors investigated the extent to which colleges of osteopathic medicine
      include evidence-based medicine education in their curricula. Information was
      obtained through a questionnaire survey, including a Likert scale. The survey was
      sent to 19 colleges of osteopathic medicine for completion. Twelve responses were
      received within the time limits of this cross-sectional study, yielding a 63%
      response rate. Four colleges of osteopathic medicine report that they currently
      teach evidence-based medicine within their education programs. Variations among
      the programs included the type of faculty delivering the evidence-based medicine
      course, the years in which instruction occurs, the number of hours of
      instruction, and assessment methods used. Seven additional schools have plans to
      implement evidence-based medicine into their educational programs. Suggestions
      for the design of an evidence-based medicine course and an evidence-based
      medicine-based curriculum are discussed in relation to the survey results.

PMID- 14686628
TI  - Random output and hospital performance.
AB  - Many countries are under pressure to reform health care financing and delivery.
      Hospital care is one part of the health system that is under scrutiny. Private
      management initiatives are a possible way to increase efficiency in health care
      delivery. This motivates the interest in developing methodologies to assess
      hospital performance, recognizing hospitals as a different sort of firm. We
      present a simple way to describe hospital production: hospital output as a change
      in the distribution of survival probabilities. This output definition allows us
      to separate hospital production from patients' characteristics. The notion of
      "better performance" has a precise meaning: (first-order) stochastic dominance of
      a distribution of survival probabilities over another distribution. As an
      illustration, we compare, for an important DRG, private and public management and
      find that private management performs better, mainly in the range of high
      survival probabilities. The measured performance difference cannot be attributed
      to input prices or to economies of scale and/or scope. It reflects pure
      technological and organisational differences.

PMID- 14686627
TI  - Non-parametric and parametric applications measuring efficiency in health care.
AB  - This paper reviews 188 published papers on frontier efficiency measurement. The
      techniques used are mainly based on non-parametric data envelopment analysis, but
      there is increasing use of parametric techniques, such as stochastic frontier
      analysis. Applications both to hospitals and wider health care areas are reviewed
      and summarised, and some meta-type analysis undertaken. Results appear to confirm
      earlier findings that public provision demonstrates less variability than
      private. The paper is meant as a resource in itself, but also points to the
      future in terms of possible directions for research in efficiency measurement in
      health care and health.

PMID- 14686629
TI  - Predicting attendance for breast screening using routinely collected data.
AB  - The aim of this paper is to predict attendance if the age range for routine
      invitation to breast screening were to be extended. The response to the most
      recent screening invitation is modelled for women eligible for screening if the
      age range were extended. The independent variables include (i) the woman's
      characteristics: her screening history; the deprivation score of the area she
      lives in and (ii) the characteristics of the screening: whether the screening
      took place in a mobile van or at a static site; and time of the year. The
      predictive ability of the regression model is tested by goodness of fit measures
      and by predicting attendance for a holdout sample of the data and for women who
      participated in a demonstration project. The modelling of attendance is quite
      successful in that most hypothesised variables have the expected sign. Moreover,
      the predictive ability of the model is satisfactory in terms of goodness of fit
      statistics and in terms of accuracy of predictions for a holdout sample. The
      model predicts less well for the demonstration project possibly because it is
      less representative of usual screening practice.

PMID- 14686631
TI  - The impact of accessibility on the use of specialist health care in Norway.
AB  - The aim of this study is to explore to what extent the policy goal of allocating
      health care according to medical need is fulfilled in Norway. Hence, we are
      interested in studying the impact of a person's health relative to the impact of
      access to specialist care. We distinguish between services provided by public
      hospitals and services provided by private specialists financed by the National
      Insurance Scheme. While a person's self-assessed health plays a major role in the
      utilization of hospitals, we find no significant effect of this variable on the
      utilization of private specialists. The accessibility indices for specialist care
      have significant effects on the utilization of private specialists, but not on
      hospital visits and inpatient stays. The challenge to policy makers is to
      consider measures that bring the utilization of publicly funded private
      specialists in accordance with national health policy.

PMID- 14686630
TI  - Mortality from breast carcinoma among US women: the role and implications of
      socio-economics, heterogeneous insurance, screening mammography, and geography.
AB  - Despite rapid advances in medicine and beneficial lifestyle changes, the
      incidence and mortality rate of gynecologic carcinoma remains high worldwide.
      This paper presents the econometric model findings of the major drivers of breast
      cancer mortality among US women. The results have implications for public health
      policy formulation on disease incidence and the drivers of mortality risks. The
      research methodology is a fixed-effects GLS regression model of breast cancer
      mortality in US females age 25 and above, using 1990-1997 time-series data pooled
      across 50 US states and DC. The covariates are age, years schooled, family
      income, 'screening' mammography, insurance coverage types, race, and US census
      region. The regressions have strong explanatory powers. Finding education and
      income to be significantly and positively correlated with mortality supports the
      'life in the fast lanes' hypothesis of Phelps. The policy of raising a woman's
      education at a given income appears more beneficial than raising her income at a
      given education level. The relatively higher mortality rate for Blacks suggests
      implementing culturally appropriate set of disease prevention and health
      promotion programs and policies. Mortality differs across insurance types with
      Medicaid the worst suggesting need for program reform. Mortality is greater for
      women ages 25-44 years, females 40-49 years who have had screening mammography,
      smokers, and residents of some US states. These findings suggest imposing more
      effective tobacco use control policies (e.g., imposing a special tobacco tax on
      adult smokers), creating a more tractable screening mammography surveillance
      system, and designing region-specific programs to cut breast cancer mortality
      risks.

PMID- 14686632
TI  - The evolution of PBMA: towards a macro-level priority setting framework for
      health regions.
AB  - To date, relatively little work on priority setting has been carried out at a
      macro-level across major portfolios within integrated health care organizations.
      This paper describes a macro marginal analysis (MMA) process for setting
      priorities and allocating resources in health authorities, based on work carried
      out in a major urban health region in Alberta, Canada. MMA centers around an
      expert working group of managers and clinicians who are charged with identifying
      areas for resource re-allocation on an ongoing basis. Trade-offs between services
      are based on locally defined criteria and are informed by multiple inputs such as
      evidence from the literature and local expert opinion. The approach is put forth
      as a significant improvement on historical resource allocation patterns.

PMID- 14686633
TI  - The effect of activity-based financing on hospital efficiency: a panel data
      analysis of DEA efficiency scores 1992-2000.
AB  - Activity-based financing (ABF) was implemented in the Norwegian hospital sector
      from 1 July 1997. A fraction of the block grant from the state to the county
      councils has been replaced by a matching grant depending upon the number and
      composition of hospital treatments. As a result of the reform, the majority of
      county councils have introduced activity-based contracts with their hospitals.
      This paper studies the effect of activity-based funding on hospital efficiency.
      We predict that hospital efficiency will increase because the benefit from cost
      reducing efforts in terms of number of treated patients is increased under ABF as
      compared with global budgets. The prediction is tested using a panel data set
      from the period 1992-2000. Efficiency indicators are estimated by means of data
      envelopment analysis (DEA) with multiple inputs and outputs. Using a variety of
      econometric methods, we find that the introduction of ABF has improved efficiency
      when measured as technical efficiency according to DEA analysis. The result is
      less uniform with respect to the effect on cost-efficiency.

PMID- 14686634
TI  - A. Cherrie Epps named Herbert W. Nickens, MD, Award recipient.

PMID- 14686635
TI  - Monica J. Mitchell named Herbert W. Nickens, MD, Minority Faculty Fellowship
      Award recipient.

PMID- 14686636
TI  - Doris Duke Clinical Research Fellowship: report of the second annual meeting.
AB  - The second annual national meeting of the Doris Duke Charitable Foundation
      Clinical Research Fellowship for Medical Students program was held June 24 to 26,
      2003, at Cold Spring Harbor Laboratory near Long Island Sound. This 3-day meeting
      offered an opportunity for 63 of the 2002 Doris Duke clinical research fellows,
      program directors, administrators, and invited physician-scientists to present
      and share their research with one another in an informal, inspiring setting at an
      institution with a history that mirrors the development of modern American
      medical research. Following a keynote lecture by Dr. Kenneth Davis, dean of the
      Mount Sinai School of Medicine, six physician-scientists representing different
      areas of clinical research presented their work. Oral and poster presentations by
      the Doris Duke fellows of their research were interspersed throughout the meeting
      and comprised its central focus. The fellows' research spanned a broad spectrum
      of clinical research from studies translating basic research findings to those
      addressing clinical questions to epidemiologic and health outcomes studies. The
      meeting culminated in a forum entitled "'Where Do We Go from Here?' Residency
      Selection and Further Research Training in Pursuit of a Career as a Clinician
      Scientist," which was moderated by this year's clinical research fellow national
      program leader, Dr. Allyn L. Mark. The meeting celebrated the accomplishments of
      these talented medical students during their fellowship year and, it is hoped,
      instilled in them awareness that their continued efforts are important to the
      future progress of medicine.

PMID- 14686637
TI  - Mitogen-activated protein kinases in endothelial pathophysiology.
AB  - Endothelial cells continuously respond to extracellular stimuli such as chemical
      signals produced by circulating blood elements or mechanical forces such as shear
      stress. Proinflammatory cytokines, mitogens, reactive oxygen species, and shear
      stress trigger signal molecules to initiate multiple intracellular pathways,
      which often converge at mitogen-activated protein (MAP) kinase activation. The
      MAP kinase superfamily represents a burgeoning area of clinical investigation for
      treatment of various inflammatory and oncologic diseases and plays an essential
      role in mediating response to infection, ischemia/reperfusion injury, and vessel
      healing and remodeling through regulation of such diverse phenomena as
      endothelial cell proliferation, migration, apoptosis, and endothelial barrier
      function. The downstream effects of MAP kinase activation include modulation of
      gene expression via up-regulation of various transcription factors. In addition
      to these sustained effects, MAP kinases coordinate more immediate responses that
      affect dynamic cytoskeletal rearrangements necessary for cell migration and
      regulation of barrier function. This review discusses the important regulatory
      roles of MAP kinases in the vital physiologic functions of endothelium, focusing
      mainly on the role of MAP kinases in the maintenance of endothelial barrier.

PMID- 14686638
TI  - Newly emerging concepts in blood vessel growth: recent discovery of endothelial
      progenitor cells and their function in tissue regeneration.
AB  - It has recently been established that bone marrow-derived endothelial progenitor
      cells (EPCs) are recruited to the systemic circulation and, in response to
      various cytokines, pharmacologic agents, and/or tissue ischemia, incorporate into
      sites of new blood vessel growth (neovascularization). These findings have
      changed our understanding of adult neovascularization by demonstrating that both
      preexisting endothelial cells and EPCs contribute to blood vessel formation
      during adult life. The following review article highlights the discovery of EPCs,
      their relationship to various clinical diseases, and their therapeutic potential
      for augmenting blood vessel formation.

PMID- 14686639
TI  - Angiotensin-converting enzyme genotype in blacks with diabetic nephropathy:
      effects on risk of diabetes and its complications.
AB  - OBJECTIVE: Among blacks, we have observed that diabetic nephropathy (DN) is a
      more frequent primary cause of end-stage renal disease (ESRD) in women
      (approximately 50%) than in men (< 20%). In this study, we consider the role of
      the angiotensin-converting enzyme (ACE) polymorphism in determining this gender
      discrepancy and its role in the course of DN. METHODS: ACE genotype (I =
      insertion, D = deletion) was determined in consecutive consenting patients with
      type 2 diabetes mellitus and DN. Charts were subsequently reviewed for renal
      survival and its determinants (end point: time to ESRD from first clinic visit).
      RESULTS: Fifty-four patients (46 blacks) who had DN and were pre-ESRD consented:
      II = 6, ID = 31, and DD = 17. The allele frequency for D was approximately . 61
      versus .39 for the I allele and did not differ by gender. Renal disease at
      presentation to the renal clinic was significantly worse in II. Twenty-one
      patients reached ESRD (II = 4, ID = 13, DD = 4; chi2 not significant), but ACE
      genotype had no significant effect on renal survival. Initial serum creatinine
      and blood pressure over follow-up independently predicted renal survival. Among
      blacks reaching ESRD, the presence of the D allele was associated with higher
      blood pressures. Patients without a family history of diabetes (chi2, p = .01) or
      diabetic retinopathy (chi2, p = .02) were more likely to have the DD genotype.
      CONCLUSIONS: The gender discrepancy observed in rates of ESRD owing to DN in
      blacks is not likely dependent on ACE genotype. The effects of ACE genotype on
      renal disease progression were not significant; however, patients with diabetic
      nephropathy and DD genotype were less likely to have traditional risk factors for
      diabetes or diabetic nephropathy.

PMID- 14686640
TI  - Comparison of echocardiography using tissue harmonics and contrast harmonics with
      radionuclide angiography for the assessment of left ventricular function.
AB  - BACKGROUND: Left ventricular ejection fraction (LVEF) is a significant predictor
      of morbidity and mortality; however, the optimal noninvasive modality for the
      quantitative determination of LVEF is not apparent. HYPOTHESIS: We verified the
      hypothesis that the various echocardiographic methods of assessing LVEF using the
      Method of Discs with contrast (Optison human albumin microspheres; Amersham
      Health, Princeton, NJ) and visual assessment of LVEF using tissue harmonics and
      contrast harmonics compare favorably with radionuclide angiography (RNA).
      METHODS: In a prospective analysis, 24 consecutive patients scheduled to undergo
      RNA had an echocardiogram using tissue harmonics and contrast harmonics on the
      same day. LVEF was assessed by RNA by an experienced, blinded reader using manual
      determination of the region of interest. LVEF was calculated using the Method of
      Discs (Simpson's Rule) by a blinded sonographer. LVEF was visually estimated by
      two blinded readers using echocardiography with tissue harmonics and contrast
      harmonics on separate occasions. RESULTS: By linear regression analysis, LVEF
      determination by echocardiography with contrast using the Method of Discs
      correlated well with RNA (r = .835, p < .0005). Using Bland-Altman analysis, the
      second echocardiogram reader had excellent agreement with RNA, whereas the first
      reader had a mean difference of 5.25% (CI 1.3-9.2; p = .012) with visual
      assessment using tissue harmonics and a mean difference of 4.67% (CI 0.4-8.8; p =
      .031) with visual assessment using contrast harmonics compared with RNA. Thus, a
      small difference in agreement between RNA and echocardiographic visual estimation
      was noted that appeared to be primarily reader dependent. CONCLUSIONS: LVEF
      determination with echocardiography with contrast using the Method of Discs
      correlated well with RNA and provided agreement across a range of cardiac
      functions. Visual echocardiographic assessment of LVEF with both tissue harmonics
      and contrast harmonics correlated well with RNA, but contrast harmonics did not
      appear to offer an advantage over tissue harmonics alone.

PMID- 14686641
TI  - Controlling blood pressure in 50% of all hypertensive patients: an achievable
      goal in the healthy people 2010 report?
AB  - BACKGROUND: One important objective defined in the Healthy People 2010 report was
      to improve blood pressure (BP) control to < 140/90 mm Hg in 50% of all
      hypertensive patients. Because the US population is becoming older, more obese,
      and ethnically diverse, the health and economic benefits of reaching this goal
      become more valuable each year. Hypertension control rates are currently at
      approximately 31% of all hypertensives and have risen slowly and erratically
      since 1988. In the absence of a coordinated strategic plan, achieving this
      critically important goal for BP control is highly unlikely. METHODS: A selected
      literature review was undertaken to briefly assess the cardiovascular benefits of
      controlling hypertension. Greater focus was placed on variables that impact
      hypertension awareness, treatment, and control. The impact on hypertension
      control rates of theoretic changes in awareness, treatment, and control
      individually and collectively was examined. Four categories of potential barriers
      to optimizing BP control are discussed: systems, provider, patient, and treatment
      factors. RESULTS: Raising awareness to 80% of all hypertensives, ensuring
      treatment of 90% of aware hypertensives, and controlling BP to < 140/90 mm Hg in
      70% of treated patients would achieve control rates of 50%. CONCLUSIONS: The
      barriers to achieving the Healthy People 2010 goal of controlling hypertension in
      50% of all patients are formidable but appear to be resolvable with a coordinated
      strategic plan. Given projected demographic changes in the United States, the
      health and economic benefits of attaining the national goal for hypertension
      control would seem to merit a serious integrated effort.

PMID- 14686642
TI  - B chromosomes of the Podisma sapporensis Shir. (Orthoptera, Acrididae) analysed
      by chromosome microdissection and FISH.
AB  - The analysis of the distribution of repetitive DNA of the B chromosomes of
      Podisma sapporensis in the A and B chromosomes of the natural populations and in
      A chromosomes of three other species of the Podismini grasshoppers were made. DNA
      libraries of the B chromosome and the euchromatic segment of the A chromosome of
      P. sapporensis were generated by meiotic chromosome microdissection followed by
      degenerated oligonucleotide primed polymerase chain reaction (DOP-PCR). Paints
      based on these DNA-libraries were used for FISH analysis to detect localization
      of homologous sequences in A and B chromosomes of P. sapporensis from different
      natural populations. On the basis of the FISH analysis the authors suggest that
      evolution of the B chromosomes in Podisma sapporensis was associated mainly with
      the insertions of "alien DNA sequences" into ancestral A chromosome and their
      further amplification. The number of initial sites of amplifications differed in
      the different Bs, the distance between these sites also varying. Karyotype
      evolution in P. sapporensis was associated partly with the insertion of "alien
      DNA sequences" into pericentromeric chromosomal regions. Insertion into the small
      short arms of the acrocentric chromosomes followed, with the DNA amplification
      leading to the formation of the additional C-heterochromatic arms or euchromatic
      like regions of different size.

PMID- 14686643
TI  - C-heterochromatin and extra (B) chromosome distribution in six species of the
      Nabis (Heteroptera, Nabidae) with the modal male karyotype 2n = 16 + XY.
AB  - The basic male karyotype of the six Nabis species (Heteroptera, Nabidae) is
      confirmed as being 2n=16+XY. The chromosomes are holokinetic while male meiosis
      is achiasmatic. The sex chromosomes undergo postreduction and in second metaphase
      show distance pairing, registered in all nabid species examined so far. Using C
      banding technique for the first time in the family Nabidae, the heterochromatin
      was revealed on chromosomes of six species. The species showed different amount
      and distribution of C-heterochromatin. Only in Nabis (Dolichonabis) limbatus did
      the C-bands distribution make possible the identification of every chromosome
      pair in the karyotype. In other species, C-bands were found in some of the
      autosomes and the X, localized either interstitially or at telomeres. Only the Y
      usually showed relative stability ofthe C-banding pattern. In four of six
      species, extra (B) chromosomes were observed and their behaviour in meiosis
      described.

PMID- 14686644
TI  - The behaviour of a multiple sex chromosome system in Dundocoris flavilineatus
      (Heteroptera: Aradidae: Carventinae) that originated by autosome-sex chromosome
      fusion.
AB  - The nominate subspecies of Dundocoris flavilineatus Jacobs occurs in indigenous
      evergreen forests over a wide area in KwaZulu-Natal and the Eastern Cape Province
      of South Africa. It has a chromosome number of 2n male = 28XY, which is the
      ancestral number for the genus. D. flavilineatus ndabeniensis, which comprises an
      isolated sibling population at Ndabeni forest in northern KwaZulu-Natal,
      possesses a multiple sex chromosome system, presumably a X1X2Y system and has a
      chromosome number of 2n male = 27X1X2Y. The system probably originated when an
      autosome and the Y-chromosome of the 28XY karyotype fused. In contrast to the
      situation previously described in the XY1Y2 system of D. nodulicarinus the
      autosomal and original Y-chromosome parts of the neo-Y chromosome seem to have a
      reciprocal influence on each other in terms of structure and staining intensity
      during prophase 1. The autosomal part of the neo-Y adopts a granulate,
      heteropycnotic, linear structure while the original Y part is less globular than
      usual in structure. The neo-X chromosome (= X2) behaves like, and stays
      isopycnotic with the autosomes. It is connected to the neo-Y by terminal
      association--probably a terminal chiasma. The sex chromosome system is post
      reductional and a sex chromosome trivalent is present in all metaphase II cells.
      The origin and behaviour of the neo-X1X2Y sex chromosome system in D.
      flavilineatus ndabeniensis are described, discussed, illustrated with
      photomicrographs and compared to the XY1Y2 system in D. nodulicarinus. Idiograms
      of the karyotypes of the two subspecies of D. flavilineatus are also presented.

PMID- 14686645
TI  - A new approach to the auchenorrhyncha (Hemiptera, Insecta) cytogenetics:
      chromosomes of the meadow spittlebug Philaenus spumarius (L.) examined using
      various chromosome banding techniques.
AB  - The karyotype of the meadow spittlebug Philaenus spumarius (L.) was studied using
      conventional chromosome staining, C- and AgNOR- banding, and fluorescent CMA3-
      and DAPI- techniques. This is the first report on differential staining of the
      holocentric chromosomes of Auchenorrhyncha. The karyotype of Ph. spumarius
      includes 2n = 22 + XX/X0. The autosomal pair 1 is large and carries a gap in
      every homologue. After silver staining, NORs were revealed in both this
      chromosome pair and a middle-sized pair, most likely 6 or 7. In spermatocyte
      meiosis, the majority of bivalents formed one chiasma each. The bivalent 1 showed
      from 1 to 4 chiasmata, the value of 1 or 2 being prevalent. Two further bivalents
      also showed two chiasmata in some cells. After C-banding, terminal and
      interstitial dot-type C-heterochromatic blocks were revealed in the chromosomes.
      In 4 of 11 studied males, the autosomal pair 1 was polymorphic for an extra
      segment attached to one of the homologues. The segment consisted of both
      heterochromatic and euchromatic portions. No defined signals were observed in any
      chromosome treated with DAPI. After CMA3- staining, bright fluorescent signals
      were obtained in the NOR-bearing chromosomes, suggesting GC-rich DNA bound to the
      NORs.

PMID- 14686646
TI  - Homologous chromosomes characteristics by sequential banding procedures in
      rainbow trout Oncorhynchus mykiss.
AB  - The development of high resolution methods of chromosome banding helped the
      finding of homologous chromosomes, detecting chromosomal abnormalities, and
      assigning the gene loci to particular chromosomes in mammals. Unfortunately,
      small and numerous fish chromosomes do not show GC rich and GC poor compartments,
      this preventing the establishment of G banding pattern. The combination of
      techniques enabling the identification of constitutive heterochromatin (C
      banding), heterochromatin resistant to restriction endonucleas, NOR bearing
      chromosomes (AgNO3 banding), or AT rich regions on chromosomes (DAPI banding) in
      sequential staining provides a better characteristic of fish chromosomes. In this
      work sequentially DAPI, DdeI, AgNO3 stained chromosomes of rainbow trout resulted
      in the characteristic banding pattern of some homologous chromosomes. Procedure
      of FISH with telomere probe and DAPI as a counterstaining fluorochrome visualized
      simultaneous hybridization signals and DAPI banding. Possibility of detection
      both FISH and DAPI signals can help in procedures of gene mapping on chromosomes.

PMID- 14686647
TI  - C-heterochromatin pattern of ten species of tetrigids (Tetrigidae, Orthoptera).
AB  - The karyotypes of species belonging to the Tetrigidae is characterised by
      structural conservatism. The standard chromosome set of T. japonica, T. simulans,
      T. bolivari, P. meridionalis, U. depressus, and F. robustus consists of 2n = 13
      acrocentric chromosomes in males and 2n = 14 in females, with a sex determining
      mechanism of X0 male and XX female. C-bands distribution often species belonging
      to 4 genera were studied. Differences in the position of C-bands and number of
      chiasma between species are discussed.

PMID- 14686648
TI  - Spermiogenesis and fine structure of the spermatozoon in a headstander, Chilodus
      punctatus (Teleostei, Characiformes, Anostomidae).
AB  - The main characteristic features of spermiogenesis in Chilodus punctatus
      (Characiformes) are rotation of the nucleus, development of a nuclear fossa,
      which extends as a narrow invagination deep into the nucleus and the way in which
      flagellum is formed. The chromatin condensation proceeds during the
      spermiogenesis from heterogeneous through homogenous and granular to a highly
      compact one present in the mature spermatozoon. Mature Ch. punctatus spermatozoon
      shows a spherical nucleus, short midpiece and flagellum with lateral fins. The
      centrioles are in perpendicular arrangement and are located in the deep nuclear
      fossa, which extends towards the anterior pole of the nucleus. The midpiece
      contains a few mitochondria, which are separated from the anterior fragment of
      flagellum by the cytoplasmic channel. Spermiogenesis and spermatozoon
      ultrastructure conform to the pattern observed in other ostariophysans, but for
      the first time the presence of lateral fins along flagellum has been documented
      in a representative of Characiformes.

PMID- 14686649
TI  - Androgens and FSH affect androgen receptor and aromatase distribution in the
      porcine ovary.
AB  - In the present study the authors investigated whether androgens could interact
      with FSH to induce aromatase and androgen receptor expression in porcine
      granulosa cells. Dissected whole porcine follicles (small, medium, and large)
      were incubated for 8 hours in M199 medium supplemented with testosterone (10(-7)
      M), FSH (100 ng/ml) or both those hormones. After incubation, the follicles were
      fixed and immunostained to visualise androgen receptor and aromatase. In cultures
      of granulosa cells isolated from small and large follicles, oestrogen secretion
      was measured by appropriate RIA. Incubation of follicles with testosterone and
      FSH increased aromatase immunoreactivity in preantral and early antral (i.e.
      small) follicles. The immunostaining for androgen receptor was slightly higher in
      medium follicles, while such hormonal stimulation had no effect on small and
      large follicles. Moreover, granulosa cells isolated from small follicles cultured
      with both testosterone and FSH produced more estradiol than control cultures (40
      pg vs. 100 pg/10(5) cells). The level was relatively close to that obtained in
      the culture of control granulosa cells isolated from large preovulatory follicles
      (105 pg/10(5) cells). These results indicate that testosterone acts
      synergistically with FSH to increase aromatase expression in the small porcine
      follicles.

PMID- 14686650
TI  - Cytogenetic alterations in Prodiamesinae species (Diptera, Chironomidae) from
      different polluted regions.
AB  - Changes in the salivary gland chromosomes are described in sibling species
      Prodiamesa olivacea Mg. and P. bureshi Michailova larvae collected from trace
      metal polluted and unpolluted areas in Bulgaria and the United Kingdom. Although
      both species from polluted and unpolluted areas show a high frequency of ectopic
      conjugations, those between arm B (telomere) and arm F occur at a significantly
      higher frequency in P. bureshi from unpolluted sites. The reasons for chromosome
      conjugations and their changes under stress conditions are discussed. Regression
      of the puffin section 2 of chromosome arm A was significantly higher in P.
      bureshi from polluted sites, suggesting that trace metal pollution represses
      transcription at that site. Also, somatic heterozygous inversions and
      deficiencies occur in chromosomes of both species at the polluted areas. Some
      deformities ofthe head capsule were observed in both species at the metal
      polluted sites. However, our data shows that the genome is a much more sensitive
      indicator of trace metal pollution than external morphology. The present authors
      suggest that measuring genotoxic damage at a cellular level provides a subtle and
      cost-effective indicator of trace metal pollution.

PMID- 14686651
TI  - Comparative analysis of alphaglobin and carbonic anhydrase I-cDNAs of the opossum
      Monodelphis domestica with related vertebrate sequences.
AB  - Alphaglobin and carbonic anhydrase I coding sequences and part of their flanking
      untranslated regions were isolated from a cDNA library of the opossum Monodelphis
      domestica. This paper describes their characteristics and presents a brief
      phylogenetic analysis of these sequences and related ones.

PMID- 14686652
TI  - Phylogenetic relationships of Paramecium jenningsi strains (classical analysis
      and RAPD studies).
AB  - The present studies with application of classical strain crosses and RAPD-PCR
      analyses showed the existence of different genetic species (syngens) within
      Paramecium jenningsi. So far the existence of only one syngen has been accepted.
      It was found that strains from Saudi Arabia, India, and China compose one genetic
      species (syngen 1) and six strains from Japan compose second genetic species
      (syngen 2).

PMID- 14686653
TI  - Noninvasive fluorescent screening of microinjected bovine embryos to predict
      transgene integration.
AB  - Most transgenic domestic animals are generated by direct microinjection of DNA
      fragments into zygote pronuclei. It has generally been assumed that the majority
      of integration events should occur prior to the first round of chromosomal DNA
      replication. The aim of this study was to investigate the expression of GFP in
      bovine preimplantation embryos by using a gfp reporter gene consisting of chicken
      beta-actin promoter, the CMV-IE enhancer, gfp cDNA (EGFP) (732 bp) and rabbit
      beta-globin polyadenylation sequences. In five experiments 302 bovine zygotes
      were injected while 75 served as a control. The fluorescence intensity was
      detected at 72 and 168 h following fertilization in bovine embryos injected with
      3 ng/microl in experiments 1-3, and injected with 5 ng/microl in experiments 4-5.
      Eight embryos were considered as expressing green fluorescence protein; 2 of them
      were 100% fluorescent after microinjection of a higher dose of the DNA; one was
      75%, two--50%, and three 25% transgenic. The mosaicism was assumed to be at 75%.
      The results indicated that the fluorescence could be analyzed at any time of
      bovine embryo development. It was therefore concluded, that chicken beta-actin
      promoter together with the CMV-IE enhancer would confer a strong expression of
      the gfp reporter gene in preimplantation bovine embryos. Therefore, using GFP
      that could be simply detected in live bovine (transgenic) embryos would be very
      promising in establishing transgenic lines of domestic animals producing in their
      fluids human therapeutic proteins.

PMID- 14686654
TI  - Genetic differences among several species of Tricladida from the relict Lake
      Ohrid as revealed by enzyme electrophoresis.
AB  - Six endemic and two widely distributed species living in Lake Ohrid were studied.
      In general, these hermaphroditic animals displayed no signs of departure from
      Hardy-Weinberg equilibrium. Genetic variation in all but one of the endemic
      species was of the same extent as that in geographically wide ranging
      invertebrates. On the other hand, the Lake Ohrid population of the common
      European species Dendrocoelum lacteum was monomorphic at all loci examined. D.
      sanctinaumi, one of the endemic species, exhibited a clear genetic subdivision
      into spring and littoral subpopulations. The genetic differentiation of Crenobia
      alpina alpina and C. a. montenigrina proved commensurable to that of well
      separated species from other genera. The data suggest that the separation of
      particular lineages in the set of Lake Ohrid endemics was widely dispersed over
      time.

PMID- 14686655
TI  - Differences in the crista dentata structure of the ischium of the third
      maxilliped in Astacus leptodactylus (Eschscholtz, 1823).
AB  - The differences in the crista dentata structure of the ischium of third
      maxilliped in different size Astacus leptodactylus (36-80 mm carapace length)
      were investigated. The results showed that four different types of crista dentata
      structure and teeth number occur in the third maxillipeds of A. leptodactylus.
      These are: (1) same number of teeth in the crista dentata of right and left third
      maxilliped, but not in the same structure, (2) different number and structure of
      teeth in the crista dentata of right and left third maxilliped, (3) same number
      and structure ofteeth in the crista dentata of right and left third maxilliped,
      (4) same sturucture of teeth in the crista dentata of right and left third
      maxilliped, but not same number of irregular teeth. In conclusion, it is believed
      that the differences in the crista dentata structure and different tooth number
      of the ischium of maxilliped cause a different cutting edge and variations in the
      food choice of A. leptodactylus.

PMID- 14686656
TI  - Effect of capsaicin and dimethyl sulphoxide (DMSO) on ion transport in isolated
      skin of frog (Rana esculenta L.).
AB  - The effects ofcapsaicin, dimethyl sulphoxide and pH changes on transport of
      sodium and/or chlorine ions in an isolated frog skin, were studied using
      electrophysiological methods, adapted to evaluation of ionic currents occurring
      in the epithelial tissues and organs. The experiment consisted in measuring
      potential difference (PD in mV) of an isolated skin of the aquatic frog, Rana
      esculenta L., placed in a Ussing apparatus. The ionic transport processes were
      modified through incubation of the tissue in Ringer solution and in Ringer
      solution supplemented with amiloride, bumetanide, and also with dimethyl
      sulphoxide. The direct effect of capsaicin and dimethyl sulphoxide (DMSO) on frog
      skin was assessed while these compounds were added to the Ussing chamber with a
      pipette and a peristaltic pump. Adaptive reactions of the tissue were assessed
      following at least 60-min exposure to those compounds. It has been demonstrated
      that amiloride-inhibited sodium ion transport and acidification of the incubation
      medium (pH 6.4) inhibited mechanically induced epithelium reactions. Both
      compounds, capsaicin and DMSO modified ionic transport processes depending on the
      mechanical stimulation.

PMID- 14686657
TI  - Effects of Cu2+, CrO4(2-), Co2+ and Pb2+ on the monovalent ion content of
      goldfish (Carassius auratus gibelio) tissues studied by X-ray microanalysis.
AB  - Carassius auratus gibelio was chosen as an organism with a high level of
      tolerance against heavy metal to investigate changes in monovalent ions content
      in its tissues. Fish were kept in 10 ppm Cu2+ (3h), CrO4(2-) (96h), Co2+ (96h),
      Pb2+ (8h) and control (96h) solutions, then tissues were dissected and prepared
      for X-ray microanalysis. K+, Na+ and Cl- concentration was measured and
      calculated. Short periods of time of fish acclimation to Cu2+ (3h) and Pb2+ (8h)
      caused fish to suffocate as a consequence of heavy metal ions binding to gill
      mucopolisaccharides. Cl- and Na+ content decreased after Cu2+ treatment in kidney
      cells and muscle fibers, and so did K+ concentration in gill cells in comparison
      to control. After that CrO4(2-) ions acclimation changes in all tissues and in
      all measured ions were observed. Similar effects were observed in Co2+ ions
      treatment but not for muscle fibers. Pb2+ ions caused an elevation of Cl- and Na+
      ions content in gill cells and muscle fibers but decreasing in liver and kidney
      cells in comparison to control. Changes in monovalent ions concentration are
      probably related to heavy metal ions influence on ionic pump activity, their
      interaction with metabolic enzymes, ATP production or membrane phospholipids.

PMID- 14686658
TI  - Behavioural response to an unsuitable host plant in the gypsy moth (Lymantria
      dispar L.).
AB  - To assess local differentiation in host preference, a two-choice test was
      performed on first-instar gypsy moth larvae originating from an oak and locust
      tree forest. More than 40 generations feeding on locust-tree leaves, rich in
      alkaloids, led to non-efficient discrimination of host leaves in larvae from a
      locust-tree forest. Possible causes of observed population differences are
      discussed in the present paper.

PMID- 14686659
TI  - Paramecium sexaurelia in Croatia.
AB  - The presence of Paramecium sexaurelia (two strains) was recorded in the National
      Park "Krka" in Croatia. This is the first record of the species, rare in Europe,
      in Croatia.

PMID- 14686660
TI  - Chronic constrictive pericarditis: pending issues.

PMID- 14686661
TI  - Prudent diet and preventive nutrition from pediatrics to geriatrics: current
      knowledge and practical recommendations.

PMID- 14686662
TI  - Vertical displacement of the precordial leads alters electrocardiographic
      morphology.
AB  - BACKGROUND: The present study was undertaken to assess whether the vertical
      displacement of electrodes affects the waveforms of precordial leads. METHODS AND
      RESULTS: Two hundred forty healthy, adult volunteers had a standard 12-lead
      electrocardiogram, a 12-lead electrocardiogram with the precordial leads
      displaced 2 cm cranially, and another with the precordial leads displaced 2 cm
      caudally from the standard positions. All the three sets of electrocardiograms
      were visually compared, and changes noted. One hundred twenty male and 120 female
      volunteers, 20-68 years of age, were analyzed. Fifty-four males (45.0%) and 2
      females (1.7%) showed no difference between the 3 sets of electrocardiograms,
      while 66 males (55.0%) and 118 females (98.3%) had some changes. R wave amplitude
      changes were noted in 63 male (52.5%) and 111 female (92.5%) volunteers; S wave
      amplitude changes were seen in 59 males (49.2%) and 99 females (82.5%,); T wave
      changes in 5 males (4.2%) and 3 females (2.5%); ST segment changes in 1 male
      (0.8%) and none of the females; and ORS morphologic changes in 1 male (0.8%) and
      12 females (10.0%). CONCLUSIONS: Precordial electrocardiographic waveform changes
      were seen with the vertical displacement of the precordial leads. This will have
      implications on the interpretation of serial electrocardiograms. Healthcare
      providers should take into consideration this deviation when interpreting serial
      ECGs.

PMID- 14686663
TI  - Coronary calcium and coronary artery disease: an Indian perspective.
AB  - BACKGROUND: Coronary artery calcification is a part of the development of
      atherosclerosis. It occurs exclusively in atherosclerotic arteries and can be
      used as a noninvasive marker of coronary atherosclerosis. As there is no large
      scale study on coronary calcium score reported in the Indian population till
      date, this study was undertaken for calculating the score in Indians at
      intermediate-to-high risk of coronary artery disease, and to correlate it with
      angiographically proven coronary artery disease. METHODS AND RESULTS: A total of
      388 consecutive patients who underwent coronary calcium scoring and coronary
      angiography were included in the study. Calcium scoring was performed based on a
      modification of the Agatston Score using a high-speed computed tomography scanner
      (GE CT/i scanner). Coronary calcium scores were correlated with the presence or
      absence of significant coronary artery disease (defined as > or = 70% stenosis of
      at least one major epicardial coronary artery) on angiography. Out of 388
      patients who underwent coronary angiography, 298 were found to have significant
      coronary artery disease. Mean coronary calcium score was significantly higher in
      patients with angiographically proven coronary artery disease (226.7+/-65.2) as
      compared to those who had normal angiograms (20.29+/-56.7; p value<0.0001). All
      the 72 patients who had a score > 400 had an abnormal angiogram (sensitivity
      23.1%, specificity 100%, positive predictive value 100%, and negative predictive
      value 24.1%). On the other hand, among the patients who had a score > 0, 298 were
      found to have abnormal angiograms, while 16 had normal angiograms (sensitivity
      95.5%, specificity 78.9%, positive predictive value 94.9%, and negative
      predictive value 81.1%). CONCLUSIONS: Detection of coronary calcium score by a
      helical computed tomography scanner is a useful tool for predicting the presence
      of significant coronary artery disease in intermediate-to-high risk patients. An
      absolute score of 0 has a high negative predictive value for the presence of
      coronary artery disease, and may obviate the need to perform coronary angiogram
      in intermediate-risk patients. On the other extreme, score > 400 is highly
      predictive of the presence of coronary artery disease, and virtually confirms the
      presence of significant coronary artery disease in intermediate-to-high risk
      patients.

PMID- 14686664
TI  - Prehospital delay in patients hospitalized with acute myocardial infarction in
      the emergency unit of a North Indian tertiary care hospital.
AB  - BACKGROUND: Prompt treatment of patients presenting with acute myocardial
      infarction decreases the incidence of death from early arrhythmia, and maximizes
      the potential benefit of thrombolytic therapy. Prehospital delay has been
      identified as a major obstacle to the widespread use of thrombolytic therapy. The
      aim of the present study was to examine the extent of, and factors associated
      with, delay in seeking medical care (usually thrombolytic therapy) in patients
      with acute myocardial infarction. METHODS AND RESULTS: The study was conducted in
      patients visiting the medical emergency unit of the Nehru Hospital, Post Graduate
      Institute of Medical Education and Research, Chandigarh. A total of 104 patients
      diagnosed with acute myocardial infarction were interviewed using a pre-designed
      proforma. Pain-to-door, and door-to-drug times, were the main outcome measures.
      The corrected mean (SEM) and median (range) pain-to-door times were 8.5 (0.8)
      hours and 5.2 (0.5-24) hours, respectively. Out of 104 patients, 38 did not
      receive thrombolytic therapy. In those who did not receive thrombolytic therapy,
      prior therapy at local health centers, lack of knowledge of symptoms, and
      transportation problems were the main reasons for hospital delay. The mean (SEM)
      and median (range) of door-to-drug times were 1.2 (0.1) hours and 1 (0.2-3.5)
      hours, respectively.

PMID- 14686665
TI  - Mitral valve repair for nonrheumatic mitral regurgitation.
AB  - BACKGROUND: We studied the results of mitral valve repair in patients with severe
      mitral regurgitation of nonrheumatic etiology. METHODS AND RESULTS: Between
      January 1988 and April 2002, 116 patients, of which 59 were male and 57 female,
      with severe mitral regurgitation of nonrheumatic etiology, underwent mitral valve
      repair using a variety of techniques. Their mean age was 26.4 years (range 2-67
      years). The cause of mitral regurgitation was congenital in 56 patients,
      myxomatous in 44, infective endocarditis in 7, and ischemic in 9. Ninety patients
      were in preoperative New York Heart Association class III, and 26 in class IV.
      Reparative procedures included posterior teflon felt collar annuloplasty
      (modified Cooley's) in 80 patients, chordal shortening in 37, cusp excision in
      34, cleft closure in 8, chordal transfer in 6, and neochordae in 3. The early
      mortality was 3.4% (4 patients). Follow-up ranged from 1 to 167 months (mean 47
      months), and was 95% complete. There were 2 late deaths (1.7%). Six patients
      (5.2%) underwent reoperation for severe mitral regurgitation post-repair. Of the
      remaining 104 patients, 90 (86.5%) had no or trivial mitral regurgitation at the
      last follow-up. Actuarial, reoperation-free, and event-free survival at 130
      months was 93%+/-3.6%, 89.9%+/-6%, and 69.7%+/-13.7%, respectively. Ninety-two
      patients (88.5%) were in New York Heart Association class I at the last follow
      up. CONCLUSIONS: Mitral valve repair in nonrheumatic mitral regurgitation
      patients provides satisfactory results with current surgical techniques, and is
      the preferred option in this subset of patients.

PMID- 14686667
TI  - Percutaneous balloon angioplasty of membranous obstruction of the inferior vena
      cava.
AB  - BACKGROUND: Membranous obstruction of the inferior vena cava is common in African
      and Asian countries. METHODS AND RESULTS: Between January 1999 and January 2002,
      19 patients were prospectively studied. The mean age of the patients was 38+/-6.9
      years. All of them had swelling of the abdomen and ankle edema. Five patients
      (26.3%) had jaundice, 9 (47.3%) had hepatomegaly, and 5 (26.3%) splenomegaly.
      Ultrasonography could detect the site of obstruction in 18 patients (94.7%). Vena
      cavography demonstrated obstruction of the inferior vena cava at the level of the
      diaphragm, with 2 patients (10.5%) having additional intrahepatic obstruction.
      The mean pressure gradient was 22+/-3.5 mmHg. Seventeen patients underwent
      balloon angioplasty using a Joseph balloon. The procedure was successful in 15
      patients (88.2%). The post-angioplasty mean pressure gradient was 5+/-1.4 mmHg.
      On follow-up, 3 patients (20%) developed features of restenosis: out of them, 2
      underwent successful redilatation. CONCLUSIONS: Balloon angioplasty of membranous
      obstruction of the inferior vena cava is feasible with a high success rate,
      without any rupture of the inferior vena cava.

PMID- 14686666
TI  - Prevalence of left atrial thrombus in rheumatic mitral stenosis with atrial
      fibrillation and its response to anticoagulation: a transesophageal
      echocardiographic study.
AB  - BACKGROUND: The frequency of occurrence of left atrial thrombi, and the effect of
      anticoagulation in patients with rheumatic mitral stenosis and atrial
      fibrillation is not well established. This study was conducted to evaluate the
      occurrence of left atrial body and left atrial appendage clots in patients with
      rheumatic mitral stenosis and atrial fibrillation, and to document the effect of
      long-term anticoagulation on clot dissolution. METHODS AND RESULTS: Consecutive
      patients with severe rheumatic mitral stenosis and atrial fibrillation were
      assessed by transesophageal echocardiography. Those with left atrial body or left
      atrial appendage clots were anticoagulated with oral nicoumalone. Transesophageal
      echocardiography was then repeated in patients on anticoagulation who were on
      regular follow-up, and in whom percutaneous transvenous mitral commissurotomy
      could be considered. Of the 490 patients studied, 163 had left atrial body or
      left atrial appendage clots. A repeat transesophageal echocardiographic
      examination was done in 50 patients who had optimal anticoagulation for a period
      of 6 months. Only 2 of the 17 patients who had left atrial body clots had
      successful clot dissolution after long-term anticoagulation, while the left
      atrial appendage clots disappeared in 31 of 33 patients (p<0.001). CONCLUSIONS:
      Left atrial clots are present in a third of patients with severe rheumatic mitral
      stenosis and atrial fibrillation. Isolated left atrial appendage clots in
      patients with rheumatic mitral stenosis and atrial fibrillation can disappear
      with long-term anticoagulation, while thrombi that extend into the left atrial
      body may persist despite optimal anticoagulation.

PMID- 14686668
TI  - Sonographically guided thrombin injection for the treatment of femoral artery
      pseudoaneurysm.
AB  - The formation of pseudoaneurysm in the femoral artery after cardiac
      catheterization is a well-recognized complication occurring in 1%-4% of cases. It
      is traditionally managed surgically and has a high morbidity. Prolonged
      ultrasound-guided compression of the neck of the pseudoaneurysm, and ultrasound
      guided injection of thrombin into the aneurysm are newer modalities of treatment
      especially for small aneurysms. We describe the case of a giant pseudoaneurysm of
      the right femoral artery, post-arteriography, which was successfully managed with
      ultrasonographically guided percutaneous thrombin injection.

PMID- 14686669
TI  - Stenting of a septal perforator for post-myocardial infarction angina.
AB  - Occlusion of a septal perforator branch alone, without the involvement of the
      left anterior descending coronary artery, leading to acute myocardial infarction
      is unusual. We report a case in which an isolated severely stenotic thrombus
      containing first septal artery causing intractable post-myocardial infarction
      angina was successfully dilated and stented.

PMID- 14686670
TI  - Mitral valve replacement on a beating heart.
AB  - We report the case of a patient who needed mitral valve replacement but was at a
      high risk of myocardial injury with the conventional technique (cardioplegic
      arrest on cardiopulmonary bypass). Valve replacement was carried out on a beating
      heart on cardiopulmonary bypass by perfusing the heart continuously with
      oxygenated noncardioplegic normothermic blood via the coronary sinus.

PMID- 14686671
TI  - Transcatheter closure of native pulmonary artery for the elimination of accessory
      pulmonary blood flow after bidirectional Glenn shunt.
AB  - We report a case where excessive accessory pulmonary blood flow via the native
      pulmonary valve after cavopulmonary anastomosis resulted in pulmonary
      hypertension and heart failure. This flow was successfully eliminated in the
      cardiac catheterization laboratory using an Amplazter duct occluder that was
      placed across the native pulmonary valve.

PMID- 14686672
TI  - Left atrial-coronary sinus dissociation following an attempt at radiofrequency
      ablation for a left lateral accessory pathway.
AB  - Coronary sinus electrograms generally represent the sequence of left atrial
      activation, and are very helpful in localizing and differentiating left lateral
      accessory pathway-mediated tachycardia from other supraventricular tachycardias.
      The activation of the coronary sinus from the left atrium occurs through muscle
      bridges, which may be discrete or form an intermingled continuum. These muscle
      bridges, if disconnected, may dissociate the coronary sinus from the left atrium,
      in which case the coronary sinus electrograms do not represent left atrial
      activation, and do not help to understand, or may cause misinterpretation of, the
      mechanism of supraventricular tachycardia. We report one such case of orthodromic
      supraventricular tachycardia mediated through the left lateral accessory pathway
      in which the coronary sinus got dissociated from the left atrium during
      radiofrequency ablation.

PMID- 14686673
TI  - Massive left atrial appendage aneurysm presenting as supraventricular
      tachycardia.
AB  - Left atrial appendage aneurysm is a rarely reported condition. Symptoms are
      absent in childhood and diagnosis is usually incidental. Systemic embolization or
      arrhythmia can bring these cases to medical attention. We report the case of a 12
      year-old male with massive left atrial appendage aneurysm who presented with
      effort intolerance and supraventricular arrhythmia. The diagnosis was made by
      transthoracic echocardiography. Magnetic resonance imaging and left atriogram
      were also done before surgical resection.

PMID- 14686674
TI  - Noncompacted left ventricle in association with dysplastic tricuspid valve.

PMID- 14686675
TI  - Seropositivity of Chlamydia pneumoniae and Helicobacter pylori among coronary
      heart disease patients and normal individuals in a South Indian population.

PMID- 14686676
TI  - Delayed tamponade following the sudden braking of a speeding vehicle.

PMID- 14686677
TI  - Isolation and genotypic comparison of oral streptococci from experimental
      bitemarks.
AB  - The feasibility of recovering and genotypically comparing oral bacteria from
      bitemarks for forensic purposes was assessed experimentally. Volunteers firmly
      bit their own upper arms and bitemarks were sampled at intervals to recover
      viable Streptococcus isolates. The recoverability of bacteria decreased over time
      but an average of more than one thousand viable organisms was recovered 24 hrs
      after biting, provided the site remained relatively undisturbed. Physical
      exertion, manual rubbing and application of moisturizing lotion all decreased
      bacterial recoverability compared to controls. Streptococci could also be
      recovered from bites inflicted on various fabrics. Genomic profiles (DNA
      "fingerprints") of bacteria recovered from bitemarks could be identified
      exclusively with those from the teeth of the individual responsible. These
      findings suggest that a bacterial genotyping approach to bitemark analysis could
      have forensic application in situations where the perpetrator's DNA cannot be
      recovered from an oral contact site.

PMID- 14686678
TI  - Chronological age determination based on the root development of a single third
      molar: a retrospective study based on 2513 OPGs.
AB  - The aim of this survey was to correlate chronological age with the root
      development of only one third molar using a sample of 2513 subjects of Belgian
      Caucasian origin within the age range of late 15 to 22 years. Observations were
      performed by two observers, who were calibrated for intra- and inter-rater
      reliability by means of Kappa statistics and each third molar present was scored
      according to the modified method of Gleiser and Hunt. The method used in this
      study delivered linear regression formulae based on a sole wisdom tooth, divided
      according to gender. The results revealed standard deviations similar to those
      reported in comparable publications and even to those calculated with other
      skeletal age calculation techniques.

PMID- 14686679
TI  - Oral health status of drug addicts in the Czech Republic.
AB  - Over the last decade, illicit drug use has become a very pronounced problem in
      the Czech Republic. Some branches of medicine such as psychiatry, internal
      medicine and neurology have tried to confront the situation by joint treatment of
      addicted patients. Dentistry has so far remained outside this multi-disciplinary
      care despite the fact that the status of dental and other tissues in the oral
      cavity influences general health and vice versa. The aim of the survey on the
      oral health of drug addicts that was conducted in the Czech Republic from 2000 to
      2002 was to collect data to help dental professionals contribute to the complex
      care of drug addicts. The number of addicted persons examined was 400 and the
      subgroup of drug addicts consisted of 217 subjects (mean age 23.87 yrs, SD 6.70),
      all being treated in long term hospitals. Among other oral health features
      observed, the DMFT and CPITN indices are presented in this paper. The results
      show severe dental and periodontal tissue destruction in young addicts and two
      case reports are included. The above survey indicates that dental treatment
      should become a part of standard care for addicted patients in long-term
      hospitals. Furthermore, if severe oral tissue impairment in young persons whether
      in dental practice or during autopsy is encountered a drug addiction should be
      suspected. If so, the treatment of the person or examination of the dead body
      should accordingly be adjusted.

PMID- 14686680
TI  - Digital radiography and electronic data storage from the perspective of legal
      requirements for record keeping.
AB  - In some countries physicians and dentists are required by law to keep medical and
      dental records. These records not only serve as personal notes and memory aids
      but have to be in accordance with the necessary standard of care and may be used
      as evidence in litigation. Inadequate, incomplete or even missing records can
      lead to reversal of the burden of proof, resulting in a dramatically reduced
      chance of successful defence in litigation. The introduction of digital
      radiography and electronic data storage presents a new problem with respect to
      legal evidence, since digital data can easily be manipulated and industry is now
      required to provide adequate measures to prevent manipulations and forgery.

PMID- 14686681
TI  - The needs of science vs the needs of patients: ethical concerns in cancer
      clinical trials.

PMID- 14686682
TI  - Age-related macular degeneration: evaluation and treatment.
AB  - Any patient age 50 or older with distorted vision or vision loss may have age
      related macular degeneration and should be immediately referred to an
      ophthalmologist. Early diagnosis and treatment are essential to preserve the
      current level of vision. We outline risk factors, clinical signs, what happens to
      the retina, and what treatments are currently available, as well as
      recommendations about vitamin and mineral supplementation.

PMID- 14686683
TI  - Endovascular therapy or conventional vascular surgery? A complex choice.
AB  - Endovascular therapy and open vascular surgery have advantages and disadvantages.
      A single therapeutic option is rarely ideal for all patients. Rather, the two
      options are tools that are best used selectively; their availability allows for
      therapy to be tailored to optimize patient care.

PMID- 14686684
TI  - BK polyomavirus: a newly recognized threat to transplanted kidneys.
AB  - Reactivation of latent infection with BK polyomavirus is now being recognized as
      a cause of failure of renal allografts. An increasing serum creatinine
      concentration in a kidney transplant recipient should prompt a referral for
      reevaluation by the transplant center.

PMID- 14686685
TI  - Skin rash in a transplant patient receiving multiple drugs.

PMID- 14686686
TI  - Who should be taking aspirin to prevent coronary events?
AB  - The decision to prescribe aspirin to prevent a coronary event is not
      straightforward, and requires physicians to balance the risk of a coronary event
      with the risk of adverse events from aspirin. Although evidence-based medicine
      shows the way, it does not answer all the questions, especially for patients at
      intermediate risk.

PMID- 14686687
TI  - In heart failure, all beta-blockers are not necessarily equal.
AB  - The Carvedilol or Metoprolol European Trial (COMET; Lancet 2003; 362:7-13) found
      that in patients with heart failure, survival appears to be better with
      carvedilol than with immediate-release metoprolol tartrate. Whether the target
      doses used were equivalent (carvedilol 25 mg twice daily vs metoprolol tartrate
      50 mg twice daily) has been debated, but the COMET trial shows that drugs in the
      same class do not necessarily have the same effects. Given the overwhelming
      evidence of the benefit of carvedilol, metoprolol succinate, and bisoprolol in
      patients with heart failure, we should all strive to increase the use of these
      drugs in appropriate doses.

PMID- 14686688
TI  - Acarbose for the prevention of diabetes.

PMID- 14686689
TI  - Acarbose for the prevention of diabetes.

PMID- 14686690
TI  - Origin and development of the pronephros in the chick embryo.
AB  - The process by which the pronephros develops was morphologically examined in
      chick embryos from Hamburger-Hamilton stage (ST) 8+ to ST34. The intermediate
      mesoderm, from which the pronephros arises, was first seen as a faint ridge of
      undifferentiated mesoderm between the segmental plate and lateral plate at ST8+.
      It formed a cell cord at the level of the 6th to the presumptive 13th somites at
      ST9 to ST10. This cell cord then separated into dorsal and ventral parts, the
      former becoming the nephric duct and the latter the tubules by ST14. The
      primordia of the external glomeruli (PEGs) appeared at ST15 through some
      epithelial cells protruding in the nephrostome (the opening of the nephric tubule
      into the body cavity). PEGs formed gradually in the caudal direction until ST18,
      while the pronephric tubules and PEGs in cranial locations disappeared. At this
      stage, only a few PEGs remained at the level of the 13th and 14th somites and
      these developed from ST23 to ST29 to become ultrastructurally similar to the
      glomeruli of the functional kidney. From these observations in the avian
      pronephros, we infer that the pronephric duct and tubules both form from a cell
      cord in the intermediate mesoderm and at the same time, but later develop
      differently.

PMID- 14686691
TI  - A composite poly-hydroxybutyrate-glial growth factor conduit for long nerve gap
      repairs.
AB  - There is considerable evidence that peripheral nerves have the potential to
      regenerate in an appropriate microenvironment. We have developed a novel
      artificial nerve guide composed of poly 3-hydroxybutyrate (PHB) filled with glial
      growth factor (GGF) suspended in alginate hydrogel. Gaps of 2-4 cm in rabbit
      common peroneal nerve were bridged using a PHB conduit containing either GGF in
      alginate hydrogel (GGF) or alginate alone (Alginate), or with an empty PHB
      conduit (Empty). Tissues were harvested 21, 42 and 63 days post-operatively.
      Schwann cell and axonal regeneration were assessed using quantitative
      immunohistochemistry. At 21 days, addition of GGF increased significantly the
      distance of axonal and Schwann cells regeneration in comparison with that
      observed in Alginate and Empty conduits for both gap lengths. The axons bridged
      the 2-cm GGF conduits gap by 63 days, with a comparable rate of regeneration seen
      in 4-cm conduits. Schwann cells and axonal regeneration quantity was similar for
      both gap lengths in each group. However, at all time points the quantity of
      axonal and Schwann cells regeneration in GGF grafts was significantly greater
      than in both Alginate and Empty conduits, the latter showing better regeneration
      than Alginate conduits. The results indicate an inhibitory effect of alginate on
      regeneration, which is partially reversed by the addition of GGF to the conduits.
      In conclusion, GGF stimulates a progressive and sustainable regeneration increase
      in long nerve gap conduits.

PMID- 14686693
TI  - Fos expression in serotonergic neurons in the rat brainstem following noxious
      stimuli: an immunohistochemical double-labelling study.
AB  - In order to detect whether there were different expression patterns of Fos
      protein induced by somatic or visceral noxious stimulation in the serotonergic
      neurons in the rat brainstem, an immunohistochemical double-labelling technique
      for serotonin (5-HT) and Fos was employed after subcutaneous or stomach injection
      of formalin. The two stimuli were matched in pilot experiments to produce maximum
      Fos expression. The expression of Fos protein in 5-HT-containing neurons (5
      HT/Fos co-localized neurons) could be observed in the ventrolateral subdivision
      of the midbrain periaqueductal grey, interpeduncular nucleus, paramedian raphe
      nucleus, all of the brainstem raphe nuclei, the alpha part of the gigantocellular
      reticular nucleus and the lateral paragigantocellular reticular nucleus. The
      locations of the 5-HT/Fos co-localized neurons in the brainstem of animals
      subjected to somatic noxious stimulation were similar to those subjected to
      visceral noxious stimulation. However, the number and proportion of the 5-HT/Fos
      co-localized neurons in the median raphe nucleus and nucleus raphe obscurus of
      the rat subjected to visceral noxious stimulation were statistically greater than
      those in rats subjected to somatic noxious stimulation. These results suggest
      that serotonergic neurons in median raphe nucleus and nucleus raphe obscurus have
      a tendency to higher neuronal activity after visceral noxious stimulation.

PMID- 14686692
TI  - Wallerian degeneration in C57BL/6J and A/J mice: differences in time course of
      neurofilament and myelin breakdown, macrophage recruitment and iNOS expression.
AB  - The lower regeneration potential reported for C57BL/6J mice strain after
      peripheral nerve lesion may result from alterations in crucial events during
      Wallerian degeneration. We analysed neurofilament and myelin breakdown,
      macrophage recruitment, NADPH-diaphorase reaction and inducible nitric oxide
      synthase (iNOS) expression in transected sciatic nerves of C57BL/6J and A/J mice.
      The neurofilament volume density was lower in C57BL/6J strain mice at 1 and 3
      days after lesion, and later equalled the density observed in A/J. C57BL/6J mice
      presented a high number of cells containing myelin debris, 3 and 5 days after the
      lesion. In both strains iNOS immunoreactivity was intense in macrophages and less
      evident in Schwann cells. However, a delay in macrophage recruitment and a lower
      percentage of iNOS-expressing macrophages on the third day were observed in
      C57BL/6J mice. NADPH-diaphorase reaction disclosed a similar pattern for both
      strains until the seventh day. However, at 5 days, cells with slender processes
      involving ellipsoid segments showed a well-defined cytoplasmic labelling in
      C57BL/6J whereas in A/J most of these cells exhibited a more granular and
      disperse labelling. We propose that these differences between A/J and C57BL/6J
      strains during Wallerian degeneration may be implicated in the lower regeneration
      potential observed in the latter.

PMID- 14686694
TI  - Apoptosis during intramembranous ossification.
AB  - This paper concerns the role of apoptosis during the onset of bone histogenesis.
      Previous investigations by us performed on intramembranous ossification revealed
      the existence of two types of osteogenesis: static (SBF) and dynamic bone
      formation (DBF). During SBF, the first to occur, stationary osteoblasts transform
      into osteocytes in the same location where they differentiated, forming the
      primary spongiosa. DBF takes place later, when movable osteoblastic laminae
      differentiate along the surface of the primary trabeculae. The main distinctive
      feature between SBF and DBF is that the latter involves the invasion of pre
      existing adjacent tissue, whereas the former does not. To ascertain whether
      programmed cell death during the invasive DBF process determines the fate of
      surrounding pre-existing mesenchyme differently from that occurring during the
      non-invasive SBF process, we studied apoptosis in ossification centres of tibial
      diaphysis in chick embryos and newborn rabbits with TUNEL and TEM. It emerged
      that, in both SBF and DBF, apoptosis affects mesenchymal cells located between
      the forming trabeculae and capillaries. However, apoptotic cells were observed
      more frequently during DBF than during SBF. This suggests that, during bone
      histogenesis, apoptosis, which is mostly associated with the invasive process of
      DBF, is probably dedicated to making space for advancing bone growth.

PMID- 14686695
TI  - Definition of the microvascular pattern of the normal human adult mammary gland.
AB  - The present report provides a detailed description of microvascularization in the
      normal human mammary gland, and defines two novel morphometric parameters to be
      used as a reference when angiogenesis in breast carcinoma is evaluated.
      Microvascularization was analysed by histology, immunohistochemistry and computer
      assisted analysis in a set of breast tissue samples taken from nine women, during
      the pre-ovulatory phase of the menstrual cycle. The two parameters designed for
      image analysis were: vascular density (VD): [microvessel number/(microvessel area
      + residual stromal area)] x 10 000; and vascular area ratio (VAR): [microvessel
      area/(microvessel area + residual stromal area)]. In the lobules VD (mean value
      +/- SE 2.48 +/- 0.14) and VAR (0.33 +/- 0.02) showed little variability and
      correlated significantly (P < 0.05). The areas occupied by microvessels, stroma
      and acini remained constant in all lobules (21.53 +/- 1.87%, 42.65 +/- 1.35% and
      35.14 +/- 1.57%, respectively). Microvascularization of the lobules was of a
      sinusoidal type, with large S-shaped capillaries. In the ducts VD (2.95 +/- 0.16)
      and VAR (0.29 +/- 0.03) showed little variability but did not correlate
      significantly. Microvascularization of the ducts was of a classic type, with
      capillaries normal in size and shape. The expression of oestrogen (ER) and
      progesterone (PR) receptors was analysed by immunohistochemistry and compared
      with the morphometric results. ER expression levels were in the range 20-25%
      (24.3 +/- 2.1) and 14-18% (15.4 +/- 1.5) in lobules and ducts, respectively. PR
      expression levels were in the range 10-13% (11.1 +/- 1.6) and 14-17% (15.2 +/-
      1.4), respectively. No correlation was found between ER/PR expression and
      vascularization parameters.

PMID- 14686696
TI  - Human intervertebral disc cell morphology and cytoskeletal composition: a
      preliminary study of regional variations in health and disease.
AB  - Classically, intervertebral disc cells have been described as fibrocytic in the
      anulus fibrosus and chondrocytic in the nucleus pulposus. Recent animal studies,
      however, have suggested that disc cell morphology may be more complex than
      previously considered. Here, by utilizing labelling of components of the
      cytoskeleton in combination with confocal microscopy, we have examined the
      detailed morphology of human intervertebral disc cells in pathological and non
      pathological tissue. Filamentous-actin- and vimentin-positive cells that appeared
      either fibrocytic or chondrocytic were observed in all intervertebral discs.
      However, in localized areas of the disc, stellate cells that extended multiple,
      branching cytoplasmic processes into their surrounding matrix were also seen.
      This stellate appearance formed a marked feature of disc cells regionally in
      certain pathologies, i.e. in cells of the outer anulus fibrosus in scoliotic
      discs and in inner anulus/nucleus pulposus cells in one spondylolisthetic disc.
      We conclude that the phenotypic variation of human intervertebral disc cells
      should be extended to include cells with a stellate appearance, which may be more
      prevalent in tissue that has been subjected to abnormal load or tension.

PMID- 14686697
TI  - Expanding role of chemokines and their receptors in cancer.

PMID- 14686698
TI  - Role of imatinib mesylate (Gleevec/Glivec) in gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumors are soft tissue sarcomas of the gastrointestinal
      tract that originate from mesenchymal cells. Advances in the systemic therapy of
      gastrointestinal stromal tumors are highlighted by the rapid development and
      approval of the molecularly targeted therapy imatinib mesylate (Gleevec/Glivec).
      Mutations of the KIT gene are known to be present in most gastrointestinal
      stromal tumors and result in gain of function, with permanent activation of the
      expressed KIT receptor in the absence of binding of the stem cell factor ligand.
      Imatinib is the first rationally designed selective inhibitor of specific protein
      tyrosine kinases, including KIT. Inhibiting the downstream signaling of KIT
      switches the cell balance into apoptosis. Although complete responses have seldom
      been seen up until now, imatinib has proven to be extremely effective in the
      treatment of patients with unresectable and/or metastatic gastrointestinal
      stromal tumors.

PMID- 14686699
TI  - Rituximab (Rituxan/MabThera): the first decade (1993-2003).
AB  - The first antibody approved for the treatment of cancer, rituximab
      (Rituxan/MabThera), underwent clinical development between 1993 and 1996. It
      fulfilled predictions dating back to the early 1900s regarding the therapeutic
      effect of antibodies and sparked a renewed interest in this area of research.
      Rituximab was approved, in the USA in 1997 and in Europe in 1998, for the
      treatment of patients with non-Hodgkin's lymphoma. Since then, hundreds of
      thousands of patients have been treated with rituximab. In 2002, rituximab became
      the number one anticancer drug worldwide. During its first decade of use (1993
      2003), rituximab has had an important impact on treatment strategies for lymphoma
      and other hematologic malignancies. During the 5 years following approval, its
      applications expanded beyond non-Hodgkin's lymphoma to a variety of malignant and
      non-malignant B-cell disorders. Also, as a result of its early clinical trials,
      initiatives came about that eventually led to the development of the new
      international response criteria for non-Hodgkin's lymphoma. Rituximab has been
      characterized as the most important therapeutic development of the decade.

PMID- 14686700
TI  - Surgical management of bladder cancer in 2003.
AB  - Recent advances in molecular and cell biology have led to a greater understanding
      of the basic biology of bladder cancer. However, despite these advances, surgery
      remains a key component of modern bladder cancer treatment. Endoscopy is the
      mainstay of the diagnosis and treatment of superficial bladder cancer. Adjuvant
      intravesical therapy is recommended for patients with high-risk superficial
      bladder cancer (Ta/T1 high grade). Select patients with invasive bladder cancer
      (T2/T3) are candidates for bladder-sparing approaches, incorporating
      transurethral resection of bladder tumor (TURBT), radiation and chemotherapy. The
      results and complications of endoscopic therapy are discussed. The role of
      partial cystectomy, radical cystoprostatectomy, prostate-sparing cystectomy,
      laparoscopic radical cystectomy, lymphadenectomy and urethrectomy in invasive
      bladder cancer are discussed. The tumor control outcomes and complications of
      radical cystoprostatectomy (still the gold standard) for organ-confined and node
      positive bladder cancer are reported. Surgery remains an integral part of the
      management of patients with bladder cancer. Improved understanding of the biology
      of bladder cancer, combined with better surgical techniques and safety, continues
      to improve the survival and quality of life of patients with bladder cancer.

PMID- 14686701
TI  - Antitumor effect of a novel nuclear factor-kappa B activation inhibitor in
      bladder cancer cells.
AB  - Nuclear factor (NF)-kappaB is a transcription factor that not only induces and
      controls various genes, including those of inflammatory cytokines, but also
      activates genes which suppress apoptosis. It has been clearly demonstrated that
      certain advanced human bladder cancer cells constitutively acquire the ability to
      activate NF-kappaB, which not only protects cancer cells from apoptotic cell
      death, but also upregulates the production of various cytokines that may increase
      the malignant potential of the disease and cause paraneoplastic syndromes. The NF
      kappaB inhibitors may therefore be useful as anticancer agents. An NF-kappaB
      function inhibitor, a dehydroxymethyl derivative of epoxyquinomicin C (DHMEQ),
      has recently been designed and synthesized. The effectiveness of DHMEQ against
      advanced human bladder cancer cell line KU-19-19, in which NF-kappaB is
      constitutively activated, has been investigated. The DNA-binding activity of NF
      kappaB was completely inhibited following 2-6-h exposure to 10 microg/ml of
      DHMEQ. Marked levels of apoptosis were observed 48 h after DHMEQ administration.
      These results confirmed that NF-kappaB activation maintains the viability of KU
      19-19 cells, that DHMEQ inhibited constitutively activated NF-kappaB, and,
      consequently, apoptosis was induced. However, it was still possible that DHMEQ
      caused apoptotic cell death through some other mechanism which has not yet been
      fully investigated. The authors conclude that DHMEQ could represent a new
      treatment strategy against advanced bladder cancer.

PMID- 14686702
TI  - Chemoprevention of superficial bladder cancer.
AB  - The American Cancer Society estimates that 57,400 new cases of bladder cancer
      will be diagnosed in the USA in 2003 and that approximately 70% of these cases
      will be superficial bladder tumors. Due to the high risk of recurrence, patients
      with superficial bladder cancer represent an ideal group for chemoprevention.
      Intravesical chemotherapy or immunotherapy is often administered in an attempt to
      prevent tumor recurrence in high-risk patients, although it is not without
      toxicity. A large body of evidence links diet and nutrition with bladder cancer.
      This review summarizes the efficacy of natural and synthetic agents that have
      purported chemopreventive activity.

PMID- 14686703
TI  - Combined bacillus Calmette-Guerin and interferon use in superficial bladder
      cancer.
AB  - Due to its high rate of local recurrence after transurethral surgery, superficial
      bladder cancer is often treated with adjuvant topical intravesical chemotherapy
      or biological agents, such as bacillus Calmette-Guerin or interferon-alpha.
      Recent laboratory testing has revealed that combination interferon-alpha with
      bacillus Calmette-Guerin results in remarkable synergy, affecting not only
      bladder tumors directly but also enhancing the immune response to bacillus
      Calmette-Guerin by orders of magnitude. Clinical studies are now demonstrating
      lower toxicity with combination low-dose bacillus Calmette-Guerin/interferon
      regimens, while providing a much needed salvage option for previous bacillus
      Calmette-Guerin failures.

PMID- 14686704
TI  - Evolving role of pegylated interferons in metastatic renal cell carcinoma.
AB  - Interferon (IFN)-alpha has demonstrated antitumor activity in a variety of solid
      and hematologic malignancies, including metastatic renal cell carcinoma.
      Pegylation, the process of combining a polyethylene glycol moiety to a biologic
      protein, substantially changes the pharmacokinetic profile of a drug, resulting
      in prolongation in half-life, increased area under the curve and, in some cases,
      improved efficacy. Pegylated IFN-alpha has been evaluated in chronic hepatitis C,
      chronic myelogenous leukemia and most recently in metastatic renal cell
      carcinoma. Registrational studies of pegylated IFN-alpha2a (PEGASYS) and
      pegylated IFN-alpha2b (PEG Intron) in patients with hepatitis C demonstrated
      greater efficacy with similar safety and tolerability to nonpegylated IFNs, with
      the advantage of less frequent administration. Studies evaluating these agents in
      the treatment of metastatic renal cell carcinoma and other cancers are ongoing.

PMID- 14686705
TI  - Laparoscopic surgery for renal cell carcinoma.
AB  - New minimally invasive technologies are currently being applied to the management
      of renal cell carcinoma in an effort to decrease operative time, pain, morbidity
      and hospital stay. Foremost among these is the burgeoning role of laparoscopy in
      tumor destruction and complete in vivo resection. The primary modalities in
      clinical use today are laparoscopic radical nephrectomy, laparoscopic partial
      nephrectomy, laparoscopic renal cryoablation and laparoscopic radiofrequency
      ablation. Most initial reports include only highly selected patients with
      unifocal, small, exophytic, peripheral lesions away from the collecting system.
      As experience with these techniques increases, larger and more difficult lesions
      are being approached laparoscopically, with promising anecdotal results reported.
      Laparoscopic access to the kidney may be retroperitoneal or transperitoneal.
      Complete tumor destruction with maximal preservation of unaffected nephrons
      remains the goal. Herein, an update on laparoscopic surgery for renal cell
      carcinoma is presented. For each procedure, the current indications and
      contraindications, perioperative data, complications and oncological outcomes are
      described. In the future, it appears likely that laparoscopy will play a major
      role in the established treatment options for renal cell carcinoma, with open
      surgery being reserved for specific indications.

PMID- 14686706
TI  - Cell-based immune therapy for metastatic renal cancer.
AB  - An exciting group of investigational therapies for metastatic renal cancer use
      cellular preparations. Technical advances accommodate testing strategies to
      repair, bypass or direct the immune system to defeat the pathologic absence of
      effective antitumor response. These can be organized by corresponding steps of
      the immune process: passive infusion of effectors isolated from blood, tumor or
      lymph nodes draining a vaccinated area; nonmyeloablative transplantation with
      stem cells plus lymphocytes specific for alloantigens, including tumor antigens,
      and reconstitution of antigen presentation by dendritic cells or modified tumor
      cells. Key monitoring of treatment outcome includes conventional clinical
      response measurement and also correlative assays as benchmarks of theoretically
      useful immunologic events. Broad efforts with innovative treatments may portend
      real progress for metastatic renal cancer immunotherapy.

PMID- 14686707
TI  - Colorectal cancer: screening and surveillance for high-risk individuals.
AB  - Colorectal cancer is very common and is closely related to patient age. After
      age, the second most common risk factor is family history of colon cancer. In
      fact, it is one of the most hereditable cancers. Colon cancer is preventable and
      screening has demonstrated efficacy in the reduction of both the incidence and
      the mortality from colorectal cancer. Several screening techniques are currently
      available, including endoscopy and nonendoscopic-based techniques. Screening
      strategies vary according to the individual risk of colon cancer. This paper will
      focus on the screening recommendations for patients with high-risk colon cancer.

PMID- 14686708
TI  - Diagnosis and treatment of carcinoid tumors.
AB  - Carcinoid tumors belong to the family of neuroendocrine tumors, which are usually
      slow growing with distinct biological and clinical characteristics. The incidence
      of these tumors is approximately 2.5 in 100,000 people per year. The former
      classification system of foregut, midgut and hindgut tumors is still used in
      clinical routine, although there is a new World Health Organization
      classification. Determination of the histopathology of carcinoid tumors is of
      utmost importance and involves specific immunohistochemical staining for
      chromogranin A, synaptophysin, serotonin and gastrin. Proliferation capacity
      measured by Ki67 is used to guide forthcoming medical treatment. Localization
      procedures include computerized tomography, ultrasound, magnetic resonance
      imaging, somatostatin receptor scintigraphy and positron emission tomography.
      Surgery remains the cornerstone of treatment and provides the only chance of a
      cure. Other cytoreductive procedures include radiofrequency ablation, laser
      treatment and chemoembolization. Biological treatment includes cytotoxic agents,
      such as somatostatin analogs and interferon-alpha, which should be applied in
      slow-growing neoplasms. Combination regimens including cisplatin, etoposide,
      streptozotocin and 5-fluorouracil should be reserved for treatment of highly
      proliferating tumors. Future therapy of carcinoid tumors will be based on the
      specific tumor biology and treatment will be customized for each individual
      patient. New therapies, such as antiangiogenic agents and new, long-acting
      somatostatin analogs, together with further development of tumor-targeted
      treatments, will come into clinical use in the near future.

PMID- 14686709
TI  - Radiosurgery in the treatment of malignant brain tumors.
AB  - Brain metastases are an attractive target for radiosurgery. Over a period of 6
      years, 400 patients with brain metastases have been treated with radiosurgery. Of
      these patients, 61% had solitary brain metastases and 39% had multiple brain
      metastases. Local control was achieved in 90% and improvement of severe
      neurological symptoms in 76%. The median survival time was 8 months. The
      significant prognostic factors for survival in patients with solitary brain
      metastases were age, Karnofsky performance status, severity of symptoms, extent
      of progressive malignant disease outside the brain, histology, interval between
      diagnosis of primary tumor and brain metastasis, and minimum applied dosage. The
      significant prognostic factors in patients with multiple brain metastases were
      sex, Karnofsky performance status and presence of progressive disease outside the
      brain.

PMID- 14686710
TI  - Oncogenomics: prospects for the future.
AB  - Genomics has generated a wealth of data that is now being used to identify
      additional molecular alterations associated with cancer development. Mapping
      these alterations in the cancer genome is a critical first step in dissecting
      oncological pathways. There are two ways in which cancer research has changed in
      recent years. The first is the progressive elucidation of the genomic basis of
      cancer. This has been accomplished by the generation of detailed information
      using procedures such as global expression profiling. The second is a renewed
      emphasis on the role of epigenetic modifications in the etiology of cancer.
      Changes in DNA methylation and chromatin modification patterns are some of the
      epigenetic factors that cause gene deregulation in cancer. In this article,
      current and evolving genomic applications and the hypotheses underlying the
      modality for cancer therapy will be reviewed.

PMID- 14686711
TI  - Antioxidants in cancer care: when and how to use them as an adjunct to standard
      and experimental therapies.
AB  - Cancer patients can be divided into two groups: those receiving therapy and those
      in remission carrying the risk of a second new cancer. Surgery, radiation therapy
      and chemotherapy are used for the treatment of the first group of patients;
      however, at present, there is no strategy to reduce the risk of a new cancer in
      the second group. While impressive progress in radiation therapy and chemotherapy
      has been made, the value of these modalities in tumor control may have reached a
      plateau. Therefore, additional approaches are needed to improve the efficacy of
      current cancer management. An active nutritional protocol that includes high
      doses of multiple dietary antioxidants and their derivatives, but not
      endogenously made antioxidants, as an adjunct to standard therapy is proposed,
      which may improve efficacy by increasing tumor response and decreasing toxicity.
      This protocol is in clinical trial. In addition, after completion of standard
      therapy, adopting a maintenance nutritional protocol that contains lower doses of
      antioxidants and their derivatives, together with modification in diet and
      lifestyle, may reduce the risk of recurrence of the original tumor and
      development of a second cancer. The efficacy of this protocol remains to be
      tested. In contrast, most oncologists do not recommend antioxidants during
      therapy, fearing that they may protect cancer cells against the damaging effect
      of treatment agents. These opposite recommendations are due to the fact that the
      results obtained from one experimental condition are extrapolated to another and
      no distinction between the effect of dietary and endogenously made antioxidants,
      or between doses, dose schedule, treatment period, form and number of
      antioxidants is made. This review discusses these issues and provides a
      biological and clinical rationale for the use of active and maintenance
      nutritional protocols as an adjunct to standard therapy and after therapy,
      respectively.

PMID- 14686712
TI  - The CARD15 gene mutation in Crohn disease.

PMID- 14686713
TI  - Role of the CARD15 gene in the pathogenesis of Crohn disease: phenotypic
      classification and prognostic implications.

PMID- 14686714
TI  - Experimental pain in gastroenterology: a reappraisal of human studies.

PMID- 14686715
TI  - Predictive factors of the long-term outcome in reflux esophagitis in a low
      prevalence gastroesophageal reflux disease region.
AB  - BACKGROUND: There are no data concerning the long-term outcome of patients with
      reflux esophagitis in Taiwan. In this study the outcome and the specific
      prognostic indicators associated with outcome in patients were assessed
      retrospectively, 7 years after diagnosis of esophagitis. METHODS: The study
      comprised a total of 128 patients with endoscopic esophagitis, diagnosed between
      January and June 1995, at Taichung Veterans' General Hospital. The outcome at 7
      years after diagnosis was assessed by outpatient or telephone interview. Factors
      associated with requiring long-term acid suppression therapy were analyzed.
      RESULTS: In all, 105 patients were eligible for analysis: 61 patients (58.1%)
      with LA (Los Angeles classification) grade A, 29 patients (27.6%) with grade B,
      11 patients (10.5%) with grade C and 4 patients (3.5%) with grade D esophagitis.
      Seven years after diagnosis, there were 52 patients (49.5%) with no or occasional
      reflux symptoms, 8 patients (7.6%) with occasional symptoms requiring treatment
      with histamine-2 receptor antagonists (H2RAs), 12 patients (11.4%) with
      occasional symptoms requiring treatment with proton pump inhibitors (PPIs), as
      needed, and 33 patients (31.3%) with sustained symptoms needing daily maintenance
      with PPIs. CONCLUSION: Nearly 50% of patients in Taiwan with endoscopic
      esophagitis still required treatment 7 years after diagnosis. Approximately 31%
      of patients still required daily acid suppression therapy. Presence of hiatal
      hernia and the severity of esophagitis at initial endoscopy independently were
      predictive of those who would require long-term acid suppression therapy.

PMID- 14686716
TI  - Recovery from gastric mucus depletion in the intact guinea pig mucosa.
AB  - BACKGROUND: In developed countries one-third of the population is infected with
      the gastric pathogen Helicobacter pylori. In the early stages of H. pylori
      induced gastritis, typical symptoms include gastric erosions and mucus
      depletions. Artificial mucus depletion was generated, demonstrating both
      consequent irritation and recovery processes in the mucosa. METHODS: The mucus
      depletion was examined by removing a small cylinder of mucus from the surface of
      the explanted guinea pig corpus mucosa, leaving the epithelial surface intact. pH
      microelectrodes were inserted into the mucosa in vitro, measuring the epicellular
      mucus pH, the pH(i) of the underlying epithelial cells and the pH inside the
      gastric glands during mucus regeneration. Using infrared microscopy, the same
      process of mucus layer renewal was followed in anaesthetized animals. RESULTS:
      The depletion exposed the tissue surface to low luminal pH levels. At a luminal
      pH of 2.5, a decrease was observed in the crypt outlet pH and surface cell pH(i),
      while deeper cells were less affected. However, a subsequent neutralization in
      the deep gland lumen was found. During the repair process, a quarter of the mucus
      layer was regenerated within the first 5 min. This newly secreted mucus formed a
      structure similar to that before depletion. Within 45 min, pH(i) and tissue-near
      pH values had fully recovered. CONCLUSION: Following mucus depletion, there is a
      decrease in surface cell pH(i) and crypt outlet pH values. The repair process is
      then characterized by extensive mucus secretion and local cessation of acid
      secretion.

PMID- 14686717
TI  - Best cut-off values for [14C]-urea breath tests for Helicobacter pylori
      detection.
AB  - BACKGROUND: The 'test and treat' strategy for Helicobacter pylori is recommended
      in dyspeptic patients under 55 years of age with no alarm symptoms. Reliable non
      invasive tests are therefore needed. The aim of this study was to assess the pre-
      and post-treatment accuracy of a low dose (1 microCi [37kBq]), short collecting
      time [14C]-UBT (urea breath test) in diagnosing H pylori infection, examining
      different methods to analyse the best cut-off points. METHODS: The study included
      119 patients. Endoscopy and [14C]-UBT were performed in the pre- and post
      treatment setting. [14C]-UBT results were expressed in three different ways: 1)
      the measured disintegrations per minute (dpm) at sample time, 2) the difference
      (D) in dpm between sample time and the dpm at T0, 3) the ratio of dpm at sample
      time to dpm at T0. RESULTS: Seventy-six out of the 119 patients (63.9%; 95% CI:
      54.9 to 71.9) were infected. Seventy-three (96%) patients completed the follow
      up. The most accurate results in both pre- (sensitivity 95.9%; specificity 97.7%)
      and post-treatment (sensitivity 90.9%; specificity 100%) were obtained using the
      difference (D) in dpm between sample time at T0 and at T12.5. CONCLUSION: A low
      dose [14C]-UBT, with a short collecting time, is a reliable method to evaluate H.
      pylori infection in both the pre- and post-treatment setting.

PMID- 14686718
TI  - Endosonography in the evaluation of anal function after primary repair of a third
      degree obstetric tear.
AB  - BACKGROUND: Disruption of the anal sphincter occurs in 0.6%-6% of women during
      delivery and almost half have persistent defecatory symptoms despite primary
      repair. Our aim was to prospectively analyse anal endosonography and rectoanal
      manometry after primary repair of a third-degree obstetric tear in order to
      compare the findings with the clinical outcome. METHODS: Twenty-one women aged 27
      41 (mean 31.5 years) who had undergone primary suture of a third-degree
      disruption of the anal sphincter were interviewed on their pelvic floor function
      and explored by manometry and endosonography 4 months after delivery. RESULTS:
      Twelve women had anal incontinence. External sphincter defect was identified on
      endosonography in 22% continent and in 91% incontinent women (P < 0.01). The
      presence of an external sphincter defect was associated with anal incontinence in
      91.7%. Surgical repair was identified on endosonography in 88% continent women
      and in 25% incontinent women (P < 0.03). The combination of a visible surgical
      repair and absence of defect was highly associated with normal continence
      (91.7%). Squeezing pressures were higher in continent women (87 +/- 23 cm H2O)
      than in incontinent women (48 +/- 36 cm H2O; P = 0.04), but no anal pressure
      threshold could achieve better results than endosonography in predicting the
      clinical outcome. CONCLUSION: After primary repair of a third-degree obstetric
      tear, endosonographic pattern of the anal sphincter correlates with the
      continence status.

PMID- 14686719
TI  - Low concentrations of ethanol induce apoptosis in human intestinal cells.
AB  - BACKGROUND: Increased systemic levels of endotoxin have been detected in human
      alcoholics and are thought to be derived from the gut. Although a 'leaky gut' is
      considered to be a necessary factor for alcohol-induced endotoxemia followed by
      chronic liver injury, the effects of low concentrations of ethanol on intestinal
      epithelial cells have not been fully understood. The aim of this study was to
      evaluate intestinal epithelial cell death induced by acute, low concentrations of
      ethanol in an in vitro system. METHODS: The human intestinal Caco-2 cell line was
      incubated with 0%, 5%, 10% ethanol for up to 3 h. Phosphatidylserine (PS)
      externalization, caspase-mediated cytokeratin 18 (CK18) cleavage, and DNA
      fragmentation were evaluated using flow cytometry. The caspase inhibitor zVAD-fmk
      was used to test the role of caspases in ethanol-induced cell death. RESULTS:
      Treatment with 5% and 10% ethanol for 3 h led to a gradual increase in PS
      externalization. Caspase-mediated CK18 was significantly enhanced as early as 1 h
      after 10% ethanol incubation, while DNA fragmentation was detected from 2 h
      onwards. Not only caspase activation but also both PS externalization and DNA
      fragmentation were completely prevented by pretreatment with the caspase
      inhibitor. CONCLUSIONS: Apoptotic cell death in confluent Caco-2 cells was
      induced by acute and low concentrations of ethanol. These results suggest that
      clinically achievable doses of ethanol impair intestinal barrier function by
      induction of apoptosis in intestinal epithelial cells. This impairment of the
      barrier function would allow endotoxin to enter the circulation and evoke hepatic
      inflammation.

PMID- 14686720
TI  - Bacteriobilia in percutaneous transhepatic biliary drainage: occurrence over time
      and clinical sequelae. A prospective observational study.
AB  - BACKGROUND: In the diagnosis and treatment of biliary disorders, establishing
      percutaneous transhepatic biliary drainage (PTBD) is an invasive procedure that
      can potentially lead to infectious complications in both the short and long-term.
      We therefore prospectively analysed the time course and spectrum of biliary
      bacteria in patients undergoing PTBD. METHODS: Forty-nine patients (19 F, 30 M;
      mean age 64 years) with malignant (65%) or benign (35%) biliary disorders were
      included, 20 of whom had a newly established PTBD (group A), while the remaining
      29 had already had their PTBD in situ (group B) for a mean of 8 months.
      Bacteriological analyses of bile and blood were carried out, and clinical
      symptoms and laboratory values were obtained. RESULTS: Biliary bacteria were
      found in 60% of cases during the initial PTBD placement, and 24 h later this rate
      had already increased to 85%; two or more microorganisms were found in 40%
      initially and in 70% after a few days. At later PTBD exchanges, bacteriobilia was
      found in 100%, with all patients harbouring multiple organisms. Whereas the
      initial spectrum was mixed, Escherichia coli and enterococci (97% each),
      Klebsiella (73%) and Bacteroides species (37%) later predominated; Candida
      increased initially from 15% to 80%, but later decreased to 30%. Clinical signs
      of cholangitis were observed in 30% initially (no sepsis), but decreased to 6% at
      later exchanges. CONCLUSIONS: Bacteriobilia is initially a frequent, and later a
      regular, event in PTBD; however, clinically significant complications are rare
      during the long-term course and limited to the initial, more invasive, phase of
      PTBD. A knowledge of the bacterial spectrum is important for selecting
      appropriate antibiotic coverage if complications arise and/or major interventions
      such as surgery are planned.

PMID- 14686721
TI  - Protection against liver injury by PGE1 or anti-TNF-alpha is associated with a
      reduction of TNF-R1 expression in hepatocytes.
AB  - BACKGROUND: Tumour necrosis factor-alpha (TNF-5) has been shown to exacerbate or
      protect against liver injury in different experimental models. In a previous
      study, we observed that enhancement of TNF-alpha expression in hepatocytes by
      prostaglandin E1 (PGE1) pre-administration induced iNOS expression and
      cytoprotection against experimental liver injury in rats. Nevertheless, the
      reduction of TNF-alpha bioactivity by anti-TNF-alpha antibodies also reduced
      liver injury by D-GalN. The purpose of the present study was to evaluate whether
      protection by PGE1 or anti-TNF-alpha was related to a common effect on the
      membrane-bound TNF-alpha receptor expression. METHODS: Liver injury was induced
      in male Wistar rats by intraperitoneal injection of D-galactosamine (D-GalN) (1
      g/kg). PGE1 or anti-TNF-alpha was administered at 30 or 60 min before D-GalN,
      respectively. Liver injury was evaluated by alanine aminotransferase (ALT)
      activity in serum and histological examination in liver sections. TNF-alpha was
      determined by ELISA in serum. The expression of TNF-alpha receptor type 1 (TNF
      R1) and TNF-alpha receptor type 2 (TNF-R2) in hepatocytes was assessed by
      immunohistochemistry and immunoprecipitation + Western-blot analysis. RESULTS:
      PGE1 or anti-TNF-alpha reduced liver injury induced by D-GalN. Although PGE1
      enhanced and anti-TNF-alpha reduced TNF-alpha concentration in serum, both
      protective treatments reduced the expression of TNF-R1 in hepatocytes. TNF-R2 was
      not detected in our experimental conditions. CONCLUSIONS: Our study showed that
      reduction of liver injury by PGE1 or anti-TNF-alpha antibodies was related to a
      reduction of TNF-R1 expression in hepatocytes.

PMID- 14686722
TI  - Outcome following liver transplantation for primary sclerosing cholangitis in the
      Nordic countries.
AB  - BACKGROUND: Primary sclerosing cholangitis (PSC) is the most common indication
      for liver transplantation in the Nordic countries. Because these patients are
      difficult to evaluate with regard to timing of liver transplantation, it is
      important to establish predictors of post-transplant survival. METHODS: Data from
      two groups of patients receiving liver allografts during 1982-2001 were recorded:
      (a) PSC patients and (b) comparison patients. Outcome following transplantation
      has been recorded for all patients. Regression analyses have been performed for
      PSC patients to analyse predictors of patient and graft survival. RESULTS: A
      total of 245 PSC and 618 comparison patients received a first liver allograft in
      the period 1982 until the end of the study. The overall 1-, 3- and 5-year patient
      survival rates were 82%, 77% and 75%, and 80%, 77% and 74% in the PSC group and
      comparison group, respectively. Survival following transplantation has increased
      with time in both the PSC and the comparison group. Recent year of
      transplantation, no previous hepatobiliary surgery and a lower MELD score were
      predictors of survival following transplantation for PSC patients. PSC patients
      had a higher rate of re-transplantations (13% versus 8%, P = 0.01). Predictors of
      re-transplantation in PSC patients were an episode of early rejection and
      vascular thrombosis. CONCLUSION: In PSC patients, year of transplantation,
      previous hepatobiliary surgery and MELD score are predictors of survival
      following transplantation and these patients are more frequently in need of re
      transplantation compared to the comparison group.

PMID- 14686723
TI  - A prospective study of the technical feasibility of ileoscopy at colonoscopy.
AB  - BACKGROUND: Despite a well-documented diagnostic yield, ileoscopy at colonoscopy
      is not performed routinely. This is due to the perceived difficulty in intubating
      the ileocaecal valve, added procedure time and a lack of acceptance regarding
      diagnostic yield. Therefore, we conducted a study to investigate the technical
      feasibility of ileoscopy at colonoscopy. METHODS: Ileoscopy was studied
      prospectively in 120 patients undergoing diagnostic colonoscopy. After
      identification of the caecum, ileoscopy was attempted by one of four techniques.
      The time taken to pass from caecum to terminal ileum, the patient position, use
      of Hyoscine-n-butyl bromide and any ileal abnormalities were recorded in each
      case. RESULTS: Ileoscopy was successful in 117/120 (97%) cases with a median time
      of 55 s taken to intubate the ileo-caecal valve. A 'down and left' technique was
      used in most cases (74.4%). Switching the patient to supine aided ileoscopy in 24
      cases (20.4%) and Hyoscine-n-butyl bromide was considered helpful in 25 (21.4%).
      Overall, the terminal ileum was abnormal in 24 of 117 (20.5%) patients.
      CONCLUSIONS: Ileoscopy can be achieved in nearly all patients undergoing
      diagnostic colonoscopy and the added procedure time is short. Added time,
      technical difficulty and limited yield are not valid reasons for choosing not to
      perform ileoscopy.

PMID- 14686724
TI  - Sodium phosphate is superior to polyethylene glycol in bowel cleansing and
      shortens the time it takes to visualize colon mucosa.
AB  - BACKGROUND: Both sodium phosphate (NaP) and polyethylene glycol-electrolyte (PEG
      EL) have been used to cleanse the bowel prior to colonoscopy, and recent reviews
      suggest that the former is the more effective and convenient cleansing regimen.
      The aim of this study was to compare the bowel cleansing effect of NaP solution
      with that of PEG-EL solution and to evaluate whether the cleansing effect
      correlates with the time needed to perform colonoscopy. METHODS: 111 patients
      admitted for colonoscopy were randomized to receive either 90 mL oral NaP or 4
      litres of PEG-EL solution. Cleansing was scored blindly by one colonoscopist and
      the following times were recorded: caecal intubation, withdrawal and total
      colonoscopy. RESULTS: Of all the patients included in the study, 99 were
      evaluable. The mean and standard error of the mean (+/-S(chi)-) cleansing score
      was 3.64 +/- 0.16 in the NaP group and 2.69 +/- 0.9 in the PEG-EL group (P =
      0.005). The mean (+/-S(chi)-) caecal intubation times were 6.39 +/- 0.50 min and
      5.39 +/- 0.41 min (P = 0.13), the withdrawal times 4.26 +/- 0.20 min and 5.78 +/-
      0.34 min (P = 0.0001) and the total colonoscopy times 10.65 +/- 0.52 min and
      11.17 +/- 0.56 min (P = 0.50) in the NaP and PEG-EL groups, respectively. The
      subgroup of patients with a cleansing score of 3 or more was associated with
      shortened colonoscopy withdrawal time compared to the group scoring below 3.
      CONCLUSIONS: Better cleansing of the large bowel shortens colonoscopy withdrawal
      time. Sodium phosphate is a more effective bowel-cleansing regimen than
      polyethylene glycol, and the better cleansing result is associated with shortened
      colonoscopy withdrawal time.

PMID- 14686725
TI  - Anti-Saccharomyces cerevisiae antibodies and coeliac disease.

PMID- 14686726
TI  - Mucinous cystadenoma of the ascending colon: a novel presentation.
AB  - Mucinous cystadenomas usually occur in the appendix, ovaries and pancreas. This
      is the first report to describe mucinous cystadenoma of the ascending colon. A 32
      year-old female presented with abdominal pain. Radiographic studies demonstrated
      a space-occupying lesion in the ascending colon associated with intussusception.
      Right colectomy revealed a cystic mass within the ascending colon that contained
      thick mucin and was lined by mucin-producing columnar epithelium. Clinical and
      pathologic features with a brief review of the literature are presented.

PMID- 14686727
TI  - Gastric submucosal polyps: histological diagnosis is not always necessary.

PMID- 14686728
TI  - Nanomolar concentrations of epothilone D inhibit the proliferation of glioma
      cells and severely affect their tubulin cytoskeleton.
AB  - The purpose of this study was to investigate the potential effects of epothilones
      (EPOs), a new class of microtubule stabilizing cytotoxic drugs, on glioma cells
      in vitro. The effects of 1, 10 and 100 nM concentrations of EPO D in four
      malignant human glioma cell lines were measured using a microtiter-tetrazolium
      assay. Besides the cell lines U87MG, U138MG and LN405, one cell line was used,
      which had been derived from a recurrent and therapy-resistant glioblastoma in our
      laboratory. In addition, changes of the cell morphology were followed by light
      microscopy and changes in the microtubule and actin cytoskeleton were visualized
      by a confocal laser microscope. In all four human glioma cell lines, 10 and 100
      nM concentrations of the drug, applied for 96 h, lead to a highly significant
      decrease in the viable cell number (p < 0.001). A mean reduction of the viable
      cell number between 30% and 40% (60% and 90%) was observed for a drug
      concentration of 10 nM (100 nM). A round cell morphology occured in most EPO
      treated cells and the organized network of microtubules was shrunk in these round
      cells. The tubulin immunostaining now appeared amorphous and was restricted to
      small perinuclear regions. Large actin filaments also disappeared, but actin
      staining was present in the whole cytosplasm. These results prove that EPOs have
      antiproliferative effects in glioma cells and affect their tubulin cytoskeleton,
      as it was previously observed in several types of carcinoma cells.

PMID- 14686730
TI  - Metabolic patterns in meningiomas.
AB  - The aim of this investigation was to define characteristic properties of cellular
      energy metabolism in meningiomas in vitro dependent on the histological subtype.
      We analysed marker enzymes of representative metabolic pathways localized in the
      mitochondria (respiratory chain, citric acid cycle, beta-oxidation of fatty
      acids) and in the cytoplasm (glycolysis, pentose phosphate shunt). The activities
      of the intramitochondrial enzymes were significantly reduced in the meningiomas
      compared to normal cortex tissue. Glycolytic enzymes were not significantly
      different, but the marker enzyme of the pentose phosphate shunt was increased by
      a factor of 3.5-6 in the tumours. Further analysis of the histological subtypes
      showed that phosphofructokinase and lactate dehydrogenase were significantly
      increased in the anaplastic meningiomas compared to the benign subtypes.

PMID- 14686731
TI  - Images in neuro-oncology. Hemangioblastoma.

PMID- 14686729
TI  - Ligands for PPARgamma and RAR cause induction of growth inhibition and apoptosis
      in human glioblastomas.
AB  - High-grade gliomas are characterized by a rapid proliferation rate, invasiveness
      and angiogenesis. Our previous data indicated that the combination of ligands for
      peroxisome proliferator-activated receptor gamma (PPARgamma) and retinoic acid
      receptor (RAR) induces apoptosis of breast cancer cells in vitro and in a murine
      model. In this study, we have shown that 11 glioblastoma cell lines and nine
      fresh glioblastoma tissue samples from patients expressed high-levels of
      PPARgamma. In contrast, glia from nine healthy human brains expressed very low
      levels of PPARgamma. No mutations or polymorphisms of the PPARgamma gene were
      observed in these cell lines. The effect of the PPARgamma ligand Pioglitazone
      (PGZ) either in the absence or in the presence of a RAR ligand [all-trans
      retinoic acid (ATRA)] on the proliferation and apoptosis of glioblastoma cells
      was examined using two glioblastoma cell lines (N39 and DBTRG05MG). PGZ and/or
      ATRA inhibited significantly the proliferation of both cell lines. Flow cytometry
      analysis showed that G1 cell cycle arrest was induced by these ligands. In
      addition, apoptosis occurred in both cell lines treated with either PGZ or ATRA,
      which was associated with a downregulation of bcl-2 and an upregulation of bax
      proteins. An enhanced effect was observed when PGZ and ATRA were combined.
      Furthermore, treatment of fresh glioblastoma tissue from patients with PGZ,
      either alone or in combination with ATRA, induced a significant level of tumor
      cell apoptosis together with a downregulation of bcl-2 protein level as compared
      with untreated control brain tissue. Taken together, our data demonstrated that
      PGZ, either alone or in combination with ATRA, induced apoptosis and inhibited
      proliferation of glioblastoma cells, and more interestingly, induced apoptosis of
      fresh glioblastoma cells from patients. Therefore, we conclude that these ligands
      may possess adjuvant therapeutic potential for patients with glioblastoma.

PMID- 14686733
TI  - Intracranial metastasis of testicular seminoma in an HIV-positive. Case report
      and review.
AB  - We present what appears to be the first case of an intracranial metastasis from
      testicular seminoma in an HIV-positive patient. The computed tomography and
      magnetic resonance imaging appearance of the lesion mimicked meningioma or
      lymphoma. A significant increase in the risk of testicular seminoma has been
      reported in AIDS patients. Whenever there is lymph-node involvement upon
      diagnosis of testicular seminoma, intracranial metastases may appear. After
      surgical removal of an intracranial metastasis from testicular seminoma,
      radiotherapy should be considered. Chemotherapy is to be included in the
      treatment of intracranial metastases from testicular seminoma with systemic
      involvement.

PMID- 14686732
TI  - High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic
      oligodendroglioma.
AB  - PURPOSE: Anaplastic oligodendroglioma is a chemosensitive glial neoplasm. To
      improve disease control and postpone cranial radiotherapy, we designed a phase II
      study of intensive procarbazine, lomunstine and vincristine followed by high-dose
      thiotepa with autologous stem cell rescue for patients with newly diagnosed
      anaplastic or aggressive oligodendroglioma. PATIENTS AND METHODS: Sixty-nine
      patients with a median age of 42 (range: 18-67) and a median Karnofsky
      Performance Score of 90 (range: 70-100) were enrolled. Sixteen patients had a
      prior diagnosis of low-grade oligodendroglioma and 16 had mixed oligoastrocytoma
      pathology. Only patients with demonstrably chemosensitive enhancing tumors or
      those free of enhancing tumor after surgery and induction therapy were eligible
      to receive high-dose thiotepa. RESULTS: Thirty-nine patients (57%) completed the
      transplant regimen; their estimated median progression-free survival is 69 months
      and median overall survival has not been reached. Twelve transplanted patients
      (31%) relapsed. Neither histology nor prior low-grade oligodendroglioma
      correlated with relapse; however, persistent non-enhancing tumor at transplant
      conferred an increased risk of relapse (p = 0.028). The transplant regimen was
      well-tolerated; median hospital stay was 20 days (range: 7-43) with a median time
      to ANC and platelet engraftment of 10 days. Thirty patients (43%) did not receive
      high-dose thiotepa because of stable or progressive disease (n = 21), excessive
      toxicity (n = 4), refusal of further therapy (n = 2), failure to obtain insurance
      coverage (n = 2), or other (n = 1). No treatment-related or long-term
      neurotoxicity was seen in the transplanted patients. CONCLUSIONS: High-dose
      chemotherapy with stem cell rescue as initial treatment for anaplastic
      oligodendroglioma is feasible and associated with prolonged tumor control in some
      patients.

PMID- 14686734
TI  - Phase I study of topotecan in combination with concurrent radiotherapy in adults
      with glioblastoma.
AB  - A phase I study was performed to determine the maximum tolerated dose and the
      recommended dose of continuous intravenous infusion of topotecan in combination
      with radiotherapy (RT) in patients with previously untreated glioblastoma
      multiforme (GBM). Twenty patients with histologically proven GBM and 1 with
      rhabdoid tumor were enrolled. After surgery or stereotactic biopsy, patients
      received cranial RT (60 Gy/30 fractions/40 days) and 3 cycles of topotecan as
      continuous infusion (CIV) from day 1 to 5 on weeks 1, 3, and 5 during RT. The
      dose of topotecan was escalated from 0.6 to 1.0 mg/m2/day. Four dose levels were
      tested. One grade 4 thrombocytopenia was seen at level 1 (topotecan dose 0.6
      mg/m2/day; 6 patients). No dose-limiting toxicity was seen at level 2 (0.8
      mg/m2/day; 3 patients) or an intermediate level of 2 bis (0.9 mg/m2/day; 6
      patients). Six patients were included at level 3 (1.0 mg/m2/day), 4 of whom
      experienced dose-limiting toxicities, including 3 episodes of grade 4
      thrombocytopenia, 1 platelet transfusion, 1 febrile neutropenia, and 1 grade 4
      neutropenia of more than 7 days. Eighty percent of patients with GBM were alive
      at 12 months. The dose-limiting toxicity of topotecan administered as CIV for 5
      days every 2 weeks is hematological. The maximum tolerated dose is 1.0 mg/m2/day
      and the recommended dose is 0.9 mg/m2/day. A phase II trial using the recommended
      dose of topotecan is ongoing.

PMID- 14686735
TI  - Pitfalls in the assessment of disability in individuals with low-grade gliomas.
AB  - In this study, the presence of motor and cognitive disability is described in a
      cohort of patients with low-grade glioma recruited from a geographical area with
      a well-defined population located in the middle of Sweden. The study group
      consisted of 35 patients, of which 24 were evaluated by both a neurologist and a
      neuropsychologist, and 11 only by a neurologist. The test battery according to
      EFIT (Edinburgh Functional Impairment Test) was used by the neurologist to
      measure impairments of limb function, memory and speech. Patients were asked to
      self-evaluate their deficits in motor function and cognition by responding to a
      specific questionnaire. In addition, a neuropsychological test battery was used
      by an experienced neuropsychologist who had no previous contact with the
      patients. In general, motor impairment was mild and predominantly found in the
      upper limb. Neuropsychological assessment revealed moderate or severe cognitive
      impairment in more than half of the patients. This impairment was not detected by
      neurological examination, and only to some extent reported by the patients them
      selves. The results show statistical differences in cognitive function, memory
      and language as recorded by the three assessors. In conclusion, this study
      demonstrates the usefulness of neuropsychological assessment as a complement to
      neurological examination to detect cognitive dysfunction in patients with low
      grade gliomas.

PMID- 14686736
TI  - The early successful treatment of glioblastoma patients with modified boron
      neutron capture therapy. Report of two cases.
AB  - We very effectively treated two patients with recurrent glioblastoma with
      modified boron neutron capture therapy (BNCT). In this paper, we describe the
      effectiveness of this treatment, and discuss the ways in which we modified the
      treatment. A 61-year-old man had a first operation for a right temporal
      glioblastoma, followed by full-dose chemo-radiotherapy. One year after the
      operation a partial removal was performed for the recurrent tumor at the same
      site. Fifty days after the second surgery, the patient received BNCT. We used an
      epithermal neutron beam as the neutron source, and used both sodium borocapate
      and boronophenylalanine as boron compounds with the craniotomy. Forty-eight hours
      after the BNCT, the follow-up MRI was applied to estimate the early effect of
      this treatment, which showed a 70% reduction in the contrast enhanced lesion,
      compared with the pretreatment MRI. In addition, the lesion/normal brain ratio of
      thallium-SPECT had improved markedly. No serial sequelae appeared after this
      treatment, and the patient remains healthy 6 months after the treatment. A 29
      year-old young lady had a right temporal brain tumor, which was partially
      resected and followed by stereotactic radiosurgery for the residual mass. Seven
      months after the radiosurgery, a second operation was performed, which revealed
      the glioblastoma as diagnosis. We applied BNCT uneventfully for this patient with
      epithermal beam and two kinds of boron compounds as described above. For the
      treatment of the patient irradiation was applied without craniotomy with marked
      reduction of tumor volume immediately after the treatment.

PMID- 14686737
TI  - Response of neoplastic meningitis from solid tumors to oral capecitabine.
AB  - Neoplastic meningitis (NM) is a major challenge for the neuro-oncologist as it
      constitutes a relatively common clinical problem in systemic and central nervous
      system cancers, and is very difficult to treat. NM portends a significant
      worsening in prognosis. Chemotherapeutic treatment options are limited, and not
      particularly effective. We report two cases of NM from breast carcinoma and a
      third with esophageal carcinoma, which responded to treatment with capecitabine,
      an oral prodrug for 5-flurouracil. We believe capecitabine warrants further
      investigation in patients with NM. In some patients, its use may result in
      clinical and radiographic tumor responses, improved quality of life, and possibly
      increased survival.

PMID- 14686738
TI  - Anti-GAD antibody positive stiff-limb syndrome in multiple myeloma.
AB  - Although most cases of stiff-limb syndrome are unassociated with malignancy,
      occasional cases have been associated with breast and lung cancer. Only four
      reported patients have had cancer and stiff-limb syndrome associated with anti
      GAD antibodies. We report the first case of stiff-limb syndrome in a patient with
      multiple myeloma undergoing treatment with thalidomide, and explore the potential
      link to the cancer and its treatment.

PMID- 14686740
TI  - A sensitive marker for left atrial dysfunction as a risk factor of cardioembolic
      stroke after cessation of paroxysmal atrial fibrillation.

PMID- 14686739
TI  - Cauda equina paraganglioma: a review.
AB  - Although rare, cauda equina paraganglioma (CEP) is definitely established in the
      table of cauda equina tumours. There are no particular investigations to document
      its preoperative diagnosis, unless a vasomotor amine syndrome is present to guide
      the differential diagnostic spectrum. Magnetic resonance imaging is the
      examination of choice for the presurgical assessment, but there are still
      overlapping findings, mainly among CEP, ependymoma, schwannoma, and
      hemangioblastoma. It is also the only means for postoperative follow-up. Computed
      tomography may fail to reveal all intrathecal lesions. Total excision is the gold
      standard for lesions with such a benign or at least protracted clinical course,
      as observed with the CEP. In contrast to well-known oncologic principles in
      micro, ultrastructural, and immunohistochemical prediction analysis, these
      tumours behave in an independent fashion. Promising efforts are being conducted
      in immunohistochemistry and DNA search, but the mainstay of our knowledge
      regarding its natural history still stems from our sporadic observation of its
      clinical behaviour.

PMID- 14686741
TI  - Atherosclerosis in renal failure.

PMID- 14686742
TI  - Primary biliary cirrhosis and E. coli-induced pyelonephritis; are infectious
      agents related to the pathogenesis of primary biliary cirrhosis?

PMID- 14686743
TI  - Features of hepatitis E virus infection in Japan.
AB  - Hepatitis E virus (HEV) is a major cause of acute hepatitis in many developing
      countries. HEV is transmitted principally by the fecal-oral route, and water
      borne epidemics are characteristic of hepatitis E. Recently, there is growing
      consensus that HEV-associated hepatitis also occurs among individuals in
      industrialized nations who had no history of travel to endemic areas. Zoonotic
      spread of HEV has been suggested as human and swine HEV strains are closely
      related genetically and experimental cross-species infection of swine HEV to a
      chimpanzee and that of human HEV to swine have been demonstrated. This review
      describes the clinical, epidemiological and virological characteristics of
      domestic HEV infection in Japan, the genetic relatedness of Japanese human and
      swine HEV strains, and possible modes of HEV transmission, emphasizing that HEV
      should be considered in the diagnosis of acute or fulminant hepatitis of non-A,
      non-B, non-C etiology, even in patients who have not traveled abroad.

PMID- 14686744
TI  - Significance of Pseudomonas aeruginosa colonization of the gastrointestinal
      tract.
AB  - OBJECTIVE: This study was conducted to determine the association between
      gastrointestinal (GI) colonization and the development of invasive Pseudomonas
      aeruginosa infections and risk factors for acquisition of P. aeruginosa
      colonization in gut. METHODS: All stool specimens sent for microbiological
      examination were cultured for P. aeruginosa search for three years. PATIENTS AND
      MATERIALS: P. aeruginosa had been isolated from stool of 207 patients for three
      years. Of the 207 patients, 87 patients were identified P. aeruginosa-colonized
      patients. RESULTS: Forty-five (52%) were exposed to previous invasive procedures
      and eighty-three (95%) were prescribed antibiotics before the isolation of P.
      aeruginosa. Fourteen distinctive P. aeruginosa infections were developed in 13
      patients (15%). Infections associated with GI colonization included 4 pneumonia,
      4 urinary tract infection, 3 skin infection, and 3 bacteremia. The age, gender,
      underlying diseases, previous invasive procedures, and the duration of
      hospitalization were not significant. Twelve (34%) patients were diagnosed with
      ileus and three (9%) were undergoing gastrostomy during the acquisition of P.
      aeruginosa colonization in gut. CONCLUSION: Gastrointestinal disorders,
      especially obstruction and surgical interventions, are also important for the
      acquisition of by P. aeruginosa, in the GI tract.

PMID- 14686745
TI  - Direct evidence that sustained dysfunction of left atrial appendage contributes
      to the occurrence of cardiogenic brain embolism in patients with paroxysmal
      atrial fibrillation.
AB  - OBJECTIVE: The goal of this study was to investigate transesophageal
      echocardiographic (TEE) findings after the termination of atrial fibrillation to
      clarify the direct evidence for occurrence of acute cardiogenic brain embolism
      (CBE) in patients with paroxysmal atrial fibrillation (PAF). PATIENTS AND
      METHODS: Among 98 consecutive patients with CBE, we investigated TEE in 16
      patients with PAF (Group CBE, 72 +/- 10 years) within 7 days of the onset and 2
      weeks after the first study, in comparison with 15 age-matched PAF patients
      without CBE (Group N). The duration from reversal to normal sinus rhythm to first
      TEE was 6 +/- 1 days in both groups. RESULTS: There were no significant
      differences in left atrial dimension and emptying flow velocity of the left
      atrial appendage (LAA-eV) between groups. Group CBE had significantly larger LAA
      area (4.3 +/- 1.3 cm2 vs. 3.1 +/- 1.0 cm2, p < 0.05), smaller LAA fractional area
      change (LAA-FAC) (43 +/- 25% vs. 80 +/- 22%, p < 0.001), and a higher incidence
      of left atrial spontaneous echo contrast (LAA-SEC) (25% vs. 7%, p < 0.05) than
      group N, and those abnormalities in group CBE were significantly improved at the
      second TEE (LAA area: to 3.2 +/- 0.9 cm2, p < 0.05; LAA-FAC: to 84 +/- 26%, p <
      0.001; LAA-SEC: to 0%, p < 0.05), respectively. CONCLUSION: LAA-FAC is a more
      sensitive marker for LAA dysfunction than the widely used index, LAA-eV, and a
      sustained deterioration of LAA-FAC may be direct evidence for thrombus formation
      and occurrence of acute CBE in patients with PAF.

PMID- 14686746
TI  - The effect of hydrocortisone on reducing rates of restenosis and target lesion
      revascularization after coronary stenting less than 3 mm in stent diameter.
AB  - OBJECTIVE: Stenting of small coronary arteries has always been limited by high
      rates of restenosis, and restenosis has mainly been attributed to inflammatory
      reactions resulting in cell proliferation and intimal hyperplasia. Based on our
      experience for several years, we retrospectively investigated the effect of
      hydrocortisone on reducing in-stent restenosis. PATIENTS AND METHODS: Study
      population consisted of consecutive 166 patients, 221 lesions, who electively
      underwent stent implantations stent diameter less than 3 mm into coronary
      arteries between February 1999 and October 2002. We intravenously administered
      hydrocortisone before the procedure to 40 patients for preventing allergic
      reactions due to contrast material, and the effect of hydrocortisone on reducing
      restenosis was retrospectively compared with 126 patients who did not receive
      this treatment. RESULTS: There was no significant difference in the prevalence of
      diabetes mellitus, hyperlipidemia, or hypertension between the two groups. There
      was no significant difference in the type of lesion, length of stent,
      balloon/artery ratio, or initial success rate between the two groups, but stent
      diameter was significantly smaller in the hydrocortisone group compared with the
      control group. On six-month angiographic follow-up, the restenosis rate was
      significantly lower in the hydrocortisone group compared with the control group
      (16.2% vs 34.0%, respectively), and the target lesion revascularization rate was
      also significantly lower in the hydrocortisone group compared with the control
      group (13.2% vs 27.5%, respectively). CONCLUSION: These results suggest that
      intravenous administration of hydrocortisone reduces in-stent restenosis of small
      coronary arteries. Prospectively controlled trials will be necessary to confirm
      this preventive effect of hydrocortisone.

PMID- 14686747
TI  - Incidence and characteristics of pulmonary thromboembolism in Japan 2000.
AB  - OBJECTIVE: The incidence of pulmonary thromboembolism (PTE) is much lower in
      Japan than in the United States. The number of deaths from PTE, however, has
      gradually increased. The present study was designed to investigate the incidence
      and characteristics of PTE in Japan. METHODS AND MATERIALS: We sent 5,582
      questionnaires to inquire about the number of new cases of PTE between August 1,
      2000 and September 30, 2000. RESULTS: We received 1,702 replies and 205 new cases
      were registered. The number of new cases per year was 4,022 (95% confidence
      interval: 3,704-4,305) and the incidence was 32 (95% confidence interval: 29.2
      33.9) patients per 1,000,000 people per year. Main risk factors were
      immobilization, surgery, trauma, and malignancy. The mortality within a month and
      6 months was 16% and 20%, respectively. Half of the deaths within a month
      occurred on the diagnosis day. CONCLUSION: The results showed that the incidence
      of PTE in Japan 2000 tended to increase compared with that in 1996, but it was
      still much lower than that in the United States.

PMID- 14686748
TI  - Different risk factors for the maximum and the mean carotid intima-media
      thickness in hemodialysis patients.
AB  - OBJECTIVE: High-resolution B-mode ultrasonography has been widely used for the
      noninvasive assessment of atherosclerosis in hemodialysis patients. But, there
      are two major methods of carotid ultrasonography: one including plaque and the
      other excluding plaque. METHODS: The subjects were 112 hemodialysis patients (58
      men and 54 women) with a mean age of 55.8 +/- 13.0 years. The maximum intima
      media thickness (IMT) of the carotid artery (including plaque) was measured as an
      index of arterial wall thickening and atheroma formation, while the mean IMT
      (without plaque) was measured as an index of arterial wall thickening. In
      addition the value of (maximum-mean) IMT was calculated as an index of atheroma
      formation. Therefore, the independent risk factors associated with the maximum
      IMT, mean IMT, and (maximum-mean) IMT were investigated by stepwise multiple
      regression analysis. RESULTS: The independent risk factors associated with the
      maximum IMT were age, diabetes mellitus, smoking, and intact parathyroid hormone
      (PTH) (R = 0.569, p < 0.0001), while factors associated with the mean IMT were
      age, hypertension, dyslipidemia, intact PTH, and lipoprotein (a) (R = 0.602, p <
      0.0001). The independent risk factors associated with the (maximum-mean) IMT were
      age, diabetes mellitus, smoking, and intact PTH (R = 0.515, p < 0.0001).
      CONCLUSION: These findings suggest that risk factors for the maximum IMT and mean
      IMT are somewhat different in hemodialysis patients.

PMID- 14686749
TI  - Pain-related differential expression of NGF, GDNF, IL-6, and their receptors in
      human vasculitic neuropathies.
AB  - OBJECTIVE: Pain-related differential expressions of nerve growth factor (NGF),
      glial cell line-derived neurotrophic factor (GDNF) and interleukin-6 (IL-6), and
      their receptors were investigated in human vasculitic neuropathies. MATERIALS AND
      METHODS: The mRNA levels of pain-related neurotrophic factors, NGF, GDNF and IL
      6, were examined in the sural nerves of 22 painful and non-painful patients with
      acute necrotizing vasculitic neuropathies, together with their concomitant
      soluble receptors (p75, GFR(alpha)-1 and IL-6R(alpha)). RESULTS: The mRNAs for
      these factors and receptors in the lesioned nerves were up-regulated to a
      variable extent in both groups. NGF mRNA expression was more closely correlated
      with that of p75 in painful neuropathy with relatively preserved large fiber
      density, compared with non-painful neuropathy, though the NGF mRNA level in
      painful neuropathy was lower than that in non-painful neuropathy. GDNF was
      closely associated with GFR(alpha)-1 in mRNA levels regardless of the pain state,
      but IL-6 was not associated with IL-6R(alpha). CONCLUSION: The differential
      expression of neurotrophic factors and their cognate soluble receptors in human
      vasculitic neuropathy suggests that NGF, which was effectively transferred to
      sensory axons with p75, may induce pain.

PMID- 14686750
TI  - Drug-induced hepatitis due to repeated use of hair dye.
AB  - A 27-year-old Japanese man with no past history of liver disease was admitted to
      our hospital due to liver abnormalities. The patient was diagnosed with drug
      induced hepatitis, as the three episodes of hepatitis occurred just after
      repeated use of hair dye. After cessation of the hair dye use, abnormal liver
      function tests improved to within the normal range. Although hair dyes contain
      various hepatotoxic compounds, hair dye is not known to cause drug-induced
      hepatitis. Thus, in cases of liver abnormality of unknown origin, the history of
      hair dye use should be investigated.

PMID- 14686751
TI  - The hemodynamic benefit of biventricular pacing therapy on mitral regurgitation
      as demonstrated in a patient with ischemic cardiomyopathy and intermittent left
      bundle branch block.
AB  - We report a 75-year-old man with ischemic cardiomyopathy who had mitral
      regurgitation which was increased markedly by intermittent left bundle branch
      block (LBBB). He complained of angina-like chest pain that was preceded by
      episodes of LBBB. During LBBB, a marked elevation of the V wave in the pulmonary
      capillary wedge pressure was shown, and an increase in mitral and tricuspid
      regurgitation was observed with color Doppler echocardiography. Biventricular
      pacing (BVP) therapy was selected so as to protect the patient from episodes of
      LBBB. After BVP, the patient did not experience chest pain or dyspnea. This case
      sheds valuable light on the ongoing investigation of the hemodynamic benefit of
      BVP.

PMID- 14686752
TI  - A novel missense mutation of the MEN1 gene in a multiple endocrine neoplasia type
      1 patient associated with carcinoid syndrome.
AB  - We report a multiple endocrine neoplasia type 1 (MEN1) patient associated with
      carcinoid syndrome. A 50-year-old woman had parathyroid hyperplasia with primary
      hyperparathyroidism, a pancreatic tumor and carcinoid tumors in the liver and
      duodenum. The primary lesion of the carcinoid was probably the bronchus. Direct
      sequencing analysis revealed a novel missense mutation at codon 342 in exon 7
      causing an amino acid change from alanine to proline (A342P) of the MEN1 gene.
      Loss of heterozygosity (LOH) was also detected in the resected parathyroid
      tissue. This mutation appeared to play an important role in the tumorigenesis of
      the endocrine tissues in the present case.

PMID- 14686753
TI  - Growth hormone insensitivity syndrome associated with syringomyelia and type I
      Chiari malformation.
AB  - A 49-year-old man with syringomyelia and a Type I Arnold-Chiari malformation
      (Chiari-I) was diagnosed with growth hormone insensitivity syndrome (GHIS). He
      was short in stature, had high circulating levels of GH, and low circulating
      levels of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP
      3). His GH responses to the administration of growth hormone-releasing hormone
      (GHRH) and L-DOPA were normal, but his levels of IGF-I and IGFBP-3 did not
      increase after the administration of exogenous GH. Direct genomic DNA sequencing
      revealed neither a mutation nor deletion in this patient's GH receptor (GHR)
      gene, though one polymorphism was detected, indicating that his GHR gene was
      normal. This is the first reported case of an association of GHIS with
      syringomyelia and Chiari-I malformation.

PMID- 14686754
TI  - Extragonadal retroperitoneal embryonal carcinoma successfully treated with
      chemotherapy.
AB  - A 27-year-old Japanese man visited our hospital for further evaluation of
      multiple shadows on his chest X-ray. A 6 cm hard mass was palpable in the left
      lower abdominal region. Histological examination revealed that the lung tumor
      resected by the video-assisted thoracoscopic surgery was an embryonal carcinoma
      (EC). He was diagnosed as retroperitoneal EC with multiple lung metastases. He
      underwent chemotherapy with cisplatin, etoposide, and bleomycin, followed by 3
      courses. A curative surgical operation revealed that there were no malignant
      cells in the lung lesions and primary lesion. This patient responded well to
      chemotherapy and achieved complete remission by chemotherapy.

PMID- 14686755
TI  - Influenza-induced rhabdomyolysis after autologous peripheral blood stem cell
      transplantation for malignant lymphoma.
AB  - We report influenza-induced rhabodmyolysis and congestive heart failure after
      high-dose therapy and hematopoietic stem cell transplantation for malignant
      lymphoma. Four months after autologous peripheral blood stem cell transplantation
      for the treatment of malignant lymphoma, a 65-year-old Japanese man developed
      acute congestive heart failure requiring artificial ventilation and
      rahbdomyolysis. Since influenza A virus was documented from his nasal cavity, he
      was diagnosed as rhabdomyolysis and congestive heart failure induced by influenza
      A infection. Neuraminidase inhibitor (oseltamivir 150 mg/ day for 5 days) was
      administrated, and heart failure and respiratory status were improved. Our
      experience suggests that early treatment with neuraminidase inhibitor may improve
      the clinical outcome of influenza-induced rhabdomyolysis and congestive heart
      failure.

PMID- 14686756
TI  - Hypertensive brainstem encephalopathy.
AB  - A 45-year-old man developed severe arterial hypertension associated with unusual
      hyperintensity in the brainstem, around the right internal capsule and in the
      deep white matter around the bilateral anterior horn of the lateral ventricle on
      T2-weighted and fluid-attenuated inversion-recovery images. The characteristic
      clinical findings were mild left hepiparesis and altered mental status which
      corresponded to the lesions of MR imagings. The lesions improved gradually with
      improvements in hypertension, which suggested that edema could be the principal
      cause of the unusual hyperintensity on MR images.

PMID- 14686757
TI  - Improvement of sleep hypopnea by antiparkinsonian drugs in a patient with
      Parkinson's disease: a polysomnographic study.
AB  - An 80-year-old man was admitted to our hospital because of bradykinesia, muscle
      rigidity and respiratory dysfunction during sleep. Concerning bradykinesia and
      muscle rigidity, we diagnosed him as the early/moderate stage of Parkinson's
      disease without autonomic dysfunction. Polysomnography (PSG) showed a series of
      obstructive hypopneas and apneas. After administration of antiparkinsonian drugs,
      rigidity of the neck and trunk was diminished along with a drastic decrease in
      hypopnea on PSG. We consider that sleep hypopnea in this patient is caused by
      involvement of the striated musculature surrounding the upper-airway and/or
      rigidity in the trunk. These conditions are treatable with antiparkinsonian
      drugs.

PMID- 14686758
TI  - Reversible posterior leukoencephalopathy syndrome in a postpartum woman without
      eclampsia.
AB  - We report a patient who developed reversible posterior leukoencephalopathy
      syndrome (RPLS) in puerperium without preeclampsia-eclampsia or chronic
      hypertension. The woman suddenly complained of visual loss and headache 10 days
      after delivery caused by edematous lesions mainly distributed in the bilateral
      occipital lobe. Apparent diffusion coefficient map was useful for distinction of
      this vasogenic edema from cytotoxic edema due to brain infarction. Under the
      diagnosis of RPLS, we successfully treated her disease using a trinitroglycerin
      as an antihypertensive, a hyperosmolar agent, methylprednisolone, and a free
      radical scavenger. Postpartum women may have the risk of development of RPLS even
      without preeclampsia-eclampsia. Vascular endothelial dysfunction may trigger
      RPLS, in addition to acute and modest increase in systemic pressure.

PMID- 14686759
TI  - A patient with E. coli-induced pyelonephritis and sepsis who transiently
      exhibited symptoms associated with primary biliary cirrhosis.
AB  - A 28-year-old woman had chief complaints of headache and a 40 degrees C fever. At
      this time, findings indicative of inflammation including elevated CRP and
      increased WBC were observed, and E. coli was detected on blood and urine culture.
      As a result, the patient was diagnosed with pyelonephritis and sepsis.
      Furthermore, markedly increased hepatobiliary enzymes and elevated anti
      mitochondrial antibody were confirmed. The administration of antimicrobial agents
      resulted in improvement of the pyelonephritis and sepsis and normalization of
      hepatobiliary enzyme and anti-mitochondrial antibody levels. It has been
      documented that the incidence of urinary tract infection is high among patients
      with primary biliary cirrhosis (PBC). The findings obtained from the present
      patient are of considerable interest in elucidating the mechanism of onset in
      PBC.

PMID- 14686760
TI  - Cholangiocellular carcinoma with an aggressive growth and eosinophilia, which
      showed multiple myeloma in autopsy.

PMID- 14686761
TI  - Preclinical Cushing's syndrome associated with non-islet cell tumor hypoglycemia;
      an additional report.

PMID- 14686762
TI  - Valproic acid-induced hearing loss and tinnitus.

PMID- 14686763
TI  - Bilateral hilar lymph node calcification in sarcoidosis.

PMID- 14686764
TI  - Rhabdomyolysis caused by distigmine bromide.

PMID- 14686765
TI  - Trace analysis of rubidium hyperfine structure in a flame atomizer using sub
      Doppler laser wave-mixing spectroscopy.
AB  - Nonlinear laser wave mixing is a versatile spectroscopic method for trace
      elemental analysis at high spectral resolution. Sub-Doppler spectral resolution
      allows isotope and hyperfine structure measurements of some of the elements even
      when using a room-pressure analytical flame (i.e., sub-Doppler but Lorentzian
      broadened spectra). A non-planar wave-mixing optical setup offers some advantages
      as compared to the conventional planar wave-mixing setup including better signal
      collection efficiency and easier optical alignment. Using our absorption-based
      wave mixing, a detection limit of 0.05 ng/mL (i.e., 50 parts-per-trillion) is
      reported for Rb in an air/acetylene flame, while still maintaining sub-Doppler
      spectral resolution for the infrared 780.0-nm Rb transition line.

PMID- 14686766
TI  - Automated line-focused laser ablation for mapping of inclusions in stainless
      steel.
AB  - An automated line imaging arrangement for two-dimensional (2D) and three
      dimensional (3D) generation of chemical maps of inclusions in stainless steel by
      laser-induced plasma spectrometry (LIPS) is presented. The plasma was generated
      in air at atmospheric pressure by focusing a flat-top Nd:YAG laser beam operating
      at 532 nm to a microline on the sample surface. The emitted light from the
      microline plasma was projected through an imaging spectrograph onto a charge
      coupled device (CCD) detector to generate a spatially and spectrally resolved
      data set. Compositional distribution maps of inclusion constituents (Mn, Mg, Ca,
      Al, and Ti) in stainless steel of different grades have been generated.
      Comparative studies with the point-to-point LIPS mapping method have been
      performed, resulting in a 51-fold reduction in the number of pulses and analysis
      time when the microline imaging approach is employed. The results illustrate the
      capability of microline imaging LIPS for fast-automated acquisition of
      tomographic maps with spatial resolution of 50 microm between adjacent craters
      and 4.8 microm along the microline.

PMID- 14686767
TI  - Advances in the Raman depth profiling of polymer laminates.
AB  - The use of Raman microspectroscopy to depth profile multi-layered polymer
      laminates is becoming increasingly popular. However, the results are generally
      degraded by aberrations introduced by the change in refractive index at the
      air/sample interface. Recent research has suggested that the use of an immersion
      oil and suitable objective can reduce this effect. This study evaluates this
      proposal by comparing depth profiling results on a multi-layer
      poly(styrene)/poly(methylmethacrylate) (PS/PMMA) laminate polymer from both dry
      metallurgical objectives and immersion objectives (used in combination with an
      oil of suitable refractive index). The immersion technique enabled successful
      depth profiling to the full working distance of the objective (100 microm),
      showing clear and distinct variations in 11 different layers within the laminate;
      a dry metallurgical objective used for comparison achieved poor resolution of
      only two layers. This is the first demonstration of depth profiling within a
      polymer laminate to this depth. The depth profiling results are compared to
      results obtained by sectioning the PS/PMMA sample after setting it in resin.

PMID- 14686768
TI  - On confocal Raman spectroscopy of semicrystalline polymers: the effect of optical
      scattering.
AB  - A series of semicrystalline polymers has been prepared through morphological
      control. Each of these has an identical refractive index but a different, well
      defined, scattering behavior. From existing geometrical optical theories of
      confocal Raman spectroscopy, these materials should behave identically.
      Initially, the extent of scattering in each system was assessed quantitatively,
      from the near-infrared through the visible wavelength range, by UV/visible
      spectroscopy. The effect of optical scattering on the variation of intensity of
      the Raman scattered radiation with subsurface position was then examined in all
      four materials; the effect of surface roughness was also considered in the
      highest clarity system. Where surface effects are removed through careful sample
      preparation and the materials are interrogated using identical optical systems to
      mitigate against the impact of refractive index mismatch and other optical
      effects, the Raman response is strongly affected by the scattering
      characteristics of each material. A simple empirical relationship has been
      determined that adequately described all our specimens.

PMID- 14686769
TI  - Limitations of using Raman microscopy for the analysis of high-content-carbon
      filled ethylene propylene diene monomer rubber.
AB  - The effects of laser irradiation on changes to the surface chemistry and
      structure of a commercially available ethylene propylene diene monomer (EPDM)
      rubber sample after Raman microscopy analysis was investigated. The Raman
      measurements were carried out with different levels of laser power on the sample,
      ranging from 4.55 mW to 0.09 mW. The surface of the EPDM was analyzed before and
      after laser exposure using X-ray photoelectron spectroscopy (XPS) and attenuated
      total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. The
      techniques have surface probe depths of approximately < or = 10 nm and 1 microm,
      respectively. Both sets of analysis show that ingredients of the blended EPDM
      rubber "bloom" to the surface as a result of local heating that takes place due
      to the absorption of laser by carbon black during the Raman analysis. Scanning
      electron microscopy (SEM) analysis was also performed on the Raman analyzed areas
      to visually illustrate the effects created due to laser light exposure (i.e.,
      burning marks). The change in surface chemistry also occurs in regions a few
      millimeters from the exposed sites, indicating that the effect is quite long
      range. However, this phenomenon has no major influence, as far as XPS or ATR-FTIR
      results disclose, on the backbone structure of the rubber sample. The results
      indicate that precautions should be taken when analyzing complex blended polymer
      samples using Raman spectroscopy.

PMID- 14686770
TI  - Orientation effects in waveguide resonance Raman spectroscopy of monolayers.
AB  - In this paper we study the effect of molecular orientation on the observed Raman
      spectra in waveguide Raman spectroscopy. Depolarization ratios differ from those
      in 'normal' Raman spectroscopy due to the polarization properties of the guiding
      modes that excite the Raman scattering. Waveguide Raman spectra of submonolayers
      of cytochrome c and NiOEP were recorded using different polarization settings.
      The observed depolarization ratios strongly deviate from those obtained in bulk
      Raman spectra. Using the derived equations for the depolarization ratios, the
      preferred orientation angle of the molecules can be obtained from the observed
      depolarization ratios. From these results we first conclude that high-quality
      spectra of sub-monolayers can be obtained using waveguide Raman spectroscopy and
      secondly, that these spectra can be used to determine the preferred orientation
      of the molecule with respect to the waveguide surface.

PMID- 14686771
TI  - Spectral depth profiling of arbitrary surfaces by thermal emission decay-Fourier
      transform infrared spectroscopy.
AB  - We report a new spectroscopic technique that combines step-scanning Fourier
      transform infrared spectroscopy with opto-thermal transient emission radiometry
      (OTTER) in order to provide near-surface depth-resolved spectra in the range 700
      1800 cm(-1). It works nondestructively, without contact, with samples of
      arbitrary shape and size, without requiring prior preparation. The depth of
      surface probed depends on the thermal diffusivity of the sample; for organic
      materials it is approximately 10 microm. With homogeneous samples, absolute
      absorption coefficients can be measured. With two-layered samples, the technique
      proved able to distinguish between the spectral properties of the top layer and
      the substrate and to estimate the thickness of the top layer. We present a
      theoretical analysis with the main design features of the instrumentation and
      software, together with studies of homogeneous and layered samples, to validate
      the methods and illustrate the potential of the technique for practical
      applications.

PMID- 14686772
TI  - Infrared reflection spectroscopy of thin films on highly oriented pyrolytic
      graphite.
AB  - The properties of highly oriented pyrolytic graphite (HOPG) as a substrate for
      external reflection infrared spectroscopy in the mid-infrared region were
      investigated. Clean HOPG substrates, physisorbed hydrocarbon multilayers, and
      chemisorbed monolayers of p-substituted aryl radicals on HOPG were used as
      samples, and the experimental spectra were compared and complemented with the
      results of spectral simulations. From reflectivity measurements of clean HOPG
      surfaces with polarized light as a function of the light incidence angle and the
      frequency, the anisotropic optical constants n (refractive index) and k
      (absorption index) were determined for in-plane and out-of-plane directions with
      respect to the graphite basal plane. These constants express the semimetallic
      properties of HOPG, indicated by an intermediate reflectivity between a typical
      metal and a dielectric substrate and by asymmetric, distorted peak shapes in
      adsorbate film spectra, which represent a transition state between symmetrical,
      positive absorptions on metals and inverted, negative peaks on dielectric
      substrates. Regarding spectral sensitivity and surface selection rules, HOPG
      behaves much like a metal and is therefore an equally suitable substrate for
      external reflection infrared (IR) measurements.

PMID- 14686774
TI  - Examination of spectral pretreatments for partial least-squares calibrations for
      chemical and physical properties of wheat.
AB  - Use of near-infrared (NIR) diffuse reflectance on ground wheat meal for
      prediction of protein content is a well-accepted practice. Although protein
      content has a strong bearing on the suitability of wheat (Triticum aestivum L.)
      for processed foods, wheat quality, as largely influenced by the configuration
      and conformation of the monomeric and polymeric endosperm storage proteins, is
      also of great importance to the food industry. The measurement of quality by NIR,
      however, has been much less successful. The present study examines the effects
      and trends of applying mathematical transformations (pretreatments) to NIR
      spectral data before partial least-squares (PLS) regression. Running mean
      smooths, Savitzky-Golay second derivatives, multiplicative scatter correction,
      and standard normal variate transformation, with and without detrending, were
      systematically applied to an extensive set of hard red winter wheat and hard
      white wheat grown over two seasons. The studied properties were protein content,
      sodium dodecyl sulfate (SDS) sedimentation volume, number of hours during grain
      fill at temperature <24 degrees C, and number of hours during grain fill at
      temperature >32 degrees C. The size of the convolution window used to perform a
      smooth or second derivative was also examined. The results indicate that for
      easily modeled properties such as protein content, the importance of pretreatment
      was lessened, whereas for the more difficult-to-model properties, such as SDS
      sedimentation volume, wide-window (>20 points) smooth or derivative convolutions
      were important in maximizing calibration performance. By averaging 30 PLS cross
      validation trial statistics (standard error) for each property, we were able to
      ascertain the inherent modeling ability of each wheat property.

PMID- 14686773
TI  - Mid-infrared spectroscopic measurement of ionic dissociative materials in the
      metabolic pathway.
AB  - We determine the pH dependency of the mid-infrared spectra in aqueous solution of
      the organic dissociative materials in the metabolic pathway: saccharide
      phosphates (G6P, F6P), adenosine, and its phosphates (ATP, ADP, AMP). The series
      of molar absorbance spectra for these reagents were obtained in a pH range of
      about 2 to 11 with a Fourier transform infrared (FT-IR) spectrometer equipped
      with a horizontal diamond attenuated total reflection (ATR) sampling accessory.
      We also provide a method of infrared spectral extraction of ionic dissociative
      materials by performing a linear least-square fitting utilizing the formulas of
      ionic dissociation equilibrium shift, and we obtain the infrared spectrum of each
      ionic species of the dissociative materials: G6P-, G6P2-; F6P-, F6P2-; ATP2-,
      ATP3-, ATP4-; ADP-, ADP2-, ADP3-; AMP, AMP-, AMP2-; and adenosine+, adenosine0.
      The infrared spectral structure of each ionic species of the dissociative
      materials in the metabolic pathway are discussed. Additionally, the possibility
      for a quantification system of the concentrations of the organic dissociative
      materials in varying pH is suggested.

PMID- 14686775
TI  - Analysis of overlapping bands by an analytic geometric approach: the potential of
      band-stripping and the complementary matching method in extraction of band
      components from overlapping bands.
AB  - As a novel method for extracting individual band components from heavily
      overlapping bands, we propose a band stripping/complementary matching method that
      is based on first-derivative-second-derivative (D1-D2) plots of an experimental
      spectrum, coupled with a new concept called a complementary band. By using the
      concept of complement of a set, the ith band can be indirectly expressed by using
      a complementary band created by subtracting all the bands, exclusive of the ith
      estimated band, from an experimental spectrum. The degree of coincidence of both
      shapes between an estimated band and its complementary band provides a very
      suitable measure for the quality of fit for each individual band. The analysis
      method consists of two stages. The first stage is concerned with the geometric
      approach, which estimates a set of values for the parameters of a component band
      in the overlapping bands, and repeats band decomposition of the remaining bands
      in the same manner after removing the estimated band from the overlapping bands.
      The second stage is to minimize the difference between the profiles of the
      estimated band and its complementary band by a least-squares optimization and
      then determine the optimum values of the band parameters with the best-fit band
      shape. The algorithm and procedures of this method are illustrated by use of a
      synthetic spectrum consisting of a number of component bands, a background
      component, and random noise. The quality of fit is so satisfactory in terms of
      the coincidence between the individual estimated band and the corresponding
      complementary one that visual observation permits us to determine the optimum
      estimates of the band parameters and avoid potential problems of curve fitting.

PMID- 14686776
TI  - Band analysis of temperature-dependent near-infrared spectra of oleic acid in the
      pure liquid state by the analytic geometric approach.
AB  - The applicability of the band-stripping and complementary matching method has
      been demonstrated by the analysis of temperature-dependent near-infrared (NIR)
      absorption spectra in the 7500-6500 cm(-1) region of oleic acid (cis-9
      octadecenoic acid) in the pure liquid state. This method is based on first
      derivative-second derivative pair (D1-D2) plots and a new concept called the
      complementary band, cBDi, created by subtracting all the rest of the bands,
      exclusive of the ith estimated band, eBDi, from an experimental spectrum. The
      degree of coincidence of both band shapes provides a suitable measure for the
      quality of fit for each individual component band. It has been confirmed from the
      present analysis of the NIR spectra of oleic acid measured over a temperature
      range of 16-79 degrees C that the change of the peak intensity of the component
      band at around 6915 cm(-1) due to the first overtone of an O-H stretching
      vibration of the monomer has two transition points around 35 and 55 degrees C.
      Moreover, the present study has provided new insight into the analysis of
      temperature-dependent spectral variations of oleic acid. Among the three
      temperature ranges, 16-35 degrees C, 35-55 degrees C, and 55-79 degrees C, in the
      first range the band near 6915 cm(-1) shows a slight increase and in the second
      range it has a linear intensity change with a slope of 0.002 a.u./degree C. In
      the third range, a rapid increase of the peak intensity is observed. This band
      exists even at 15 degrees C (just below the melting point) and shows a shift from
      6910 to 6915 cm(-1) and a band narrowing from 85 to 80 cm(-1) (full width at half
      height) over a temperature range of 16 to 79 degrees C. Furthermore, it has been
      found that there are two broad bands at around 6835 and 6778.

PMID- 14686777
TI  - Revealing system dynamics through decomposition of the perturbation domain in two
      dimensional correlation spectroscopy.
AB  - A technique is presented to simply and effectively decompose the perturbation
      domain in two-dimensional (2D) correlation maps calculated on a given set of
      vibrational spectra. Decomposition of the perturbation domain exposes a wealth of
      kinetic information complementary to the information extracted from conventional
      2D correlation spectroscopy. It is shown that the technique produces
      "perturbation profile maps" that can be utilized in both the interpretation of
      the conventional 2D correlation maps and the independent kinetic analysis of the
      given system. Discrimination between spectral features exhibiting similar, but
      not identical, dynamics is facilitated by the decomposition, and spectral
      features exhibiting identical dynamics over the perturbation interval are quickly
      identified. Spectral features exhibiting similar dynamics over only a sub-range
      of the full perturbation are also identifiable. Interpretation of phase
      information illuminated in synchronous and asynchronous maps is simplified.
      Comparison between similar spectral features present in different samples is
      facilitated with the technique. The simplicity and ease of implementation of the
      technique make decomposition of the perturbation domain a valuable addition to
      the tools available in 2D correlation analysis.

PMID- 14686778
TI  - Identification and interpretation of generalized two-dimensional correlation
      spectroscopy features through decomposition of the perturbation domain.
AB  - Generalized two-dimensional correlation spectroscopy offers great scope for
      revealing the behavior of relationships between components of a system under
      empirical study. We have developed methods that aid in the interpretation of two
      dimensional correlation spectroscopy. These methods include reference patterns
      for two-dimensional correlation and correlation coefficient maps, their
      superposition and joint interpretation, and the use of delta functions to
      decompose them in the perturbation domain. We show how their joint use permits
      discrimination between similar two-dimensional correlation map features on the
      basis of different correlation coefficients. We also show how the decomposition
      of maps into the perturbation domain reflects the dynamic behavior of spectral
      features over the course of the perturbation and permits discrimination between
      otherwise highly similar two-dimensional correlation cross-peaks. These
      approaches simplify the interpretation of two-dimensional correlation
      spectroscopy maps and facilitate access to their rich information content.

PMID- 14686779
TI  - Determining sample differences in a sample series of complex liquid
      chromatography-diode array detector data using chemometrics.
AB  - In analytical laboratories, one often has to deal with sample series that have
      minor differences between them. For example, different batches of the same
      material may cause manufacturing problems, and quality control is an important
      issue. Another example is decomposition studies, where changes may or may not
      occur in a sample. To extract the differences between such highly related samples
      from LC-DAD (liquid chromatography-diode array detector) data is a time-consuming
      and subjective task. This paper describes an algorithm that efficiently extracts
      such differences.

PMID- 14686780
TI  - Simultaneous determination of the pesticides carbaryl and thiabendazole in
      environmental samples by a three-dimensional derivative variable-angle and a
      synchronous room-temperature phosphorescence spectroscopy.
AB  - A three-dimensional derivative variable-angle synchronous scanning (DVASS) and a
      synchronous scanning (SS) heavy-atom room-temperature phosphorimetry (HAI-RTP)
      method are reported, for the first time, to identify and quantify the spectral
      overlapping phosphorescent pesticides thiabendazole (TBZ) and carbaryl (CBL).
      These pesticides are widely used in agriculture. The phosphorescence emission of
      the two compounds was obtained using sodium sulfite as the O2 scavenger and an
      external heavy atom salt. A careful selection of these experimental variables has
      been carried out. The increase of selectivity afforded by the DVASS and the SS
      methodology permitted the demonstration of its applicability to the simultaneous
      determination of phosphorescent signals of these two pesticides with overlapping
      spectral profiles. Limits of detection ranged between 1.4 ng/mL for TBZ and 1.7
      ng/mL for CBL. The proposed method has been satisfactorily applied to the
      analysis of both pesticides in different types of water samples.

PMID- 14686781
TI  - Submicrometer spatial resolution of metal-enhanced fluorescence.
AB  - Enhanced fluorescence emission intensity from fluorescein was observed on glass
      slides covered with thin films of silver nanoparticles using a confocal laser
      scanning microscope. The silver nanoparticle film increased the emission
      intensity of fluorescein by an average of at least three-fold in the area
      studied. Statistics are given on the enhancement of individual areas of the
      silver particle film with a resolution of approximately 210 nm. A histogram of
      intensity values indicates that the enhancement appears to occur without distinct
      subpopulations, with the exception that very high intensity subpopulations may
      occur but could not be resolved. Spatial features with dimensions near or smaller
      than the resolution limit of the confocal microscope, on the silver nanoparticle
      slide that enhanced the emission of fluorescein, were found using autocorrelation
      functions. These spatial features are of the same size as those found from the
      emission of slides containing silver nanoparticles only. These spatial features
      do not appear in control slides containing fluorescein without any silver
      nanoparticles. No long-range spatial ordering of the fluorescence enhancement on
      chemcially deposited silver nanoparticle slides was detected.

PMID- 14686783
TI  - Effect of noise on the evaluation of correlation coefficients in two-dimensional
      correlation spectroscopy.

PMID- 14686782
TI  - Simultaneous monitoring of organic acids and sugars in fresh and processed apple
      juice by Fourier transform infrared-attenuated total reflection spectroscopy.
AB  - A combination of Fourier transform infrared spectroscopy (FT-IR) and chemometrics
      was used as a screening tool for the determination of sugars and organic acids
      such as sucrose, glucose, fructose, sorbitol, citric acid, and malic acid in
      processed commercial and extracted fresh apple juices. Prepared samples of
      synthetic apple juice in different constituent concentration ranges were scanned
      by attenuated total reflectance (ATR) accessory and the spectral region in the
      range between 950 and 1500 cm(-1) was selected for calibration model development
      using partial least squares (PLS) regression and principal component regression
      (PCR). The calibration models were successfully validated by high-performance
      liquid chromatography (HPLC) measurements against several commercial juice
      varieties as well as juice extracted from different apple varieties to provide an
      overall R2 correlation of 0.998. The present study demonstrates that Fourier
      transform infrared spectroscopy could be used for rapid and nondestructive
      determination of multiple constituents in commercial and fresh apple juices.
      Results indicate this approach to be a rapid and cost-effective tool for routine
      monitoring of multiple constituents in a fruit juice production facility.

PMID- 14686784
TI  - Simple algorithms for the classification of visible/near-infrared and
      hyperspectral imaging spectra of chicken skins, feces, and fecal contaminated
      skins.

PMID- 14686785
TI  - Overexpression of CYP2D6 attenuates the toxicity of MPP+ in actively dividing and
      differentiated PC12 cells.
AB  - Clonal pheochromocytoma cell lines overexpressing cytochrome P450 2D6 (CYP2D6)
      were established. CYP2D6 was localized in the endoplasmic reticulum, and its
      enzymatic activity in the microsomal fraction was confirmed by using high
      performance liquid chromatography analysis with [guanidine-14C]debrisoquine as a
      substrate. Overexpression of CYP2D6 protected both actively dividing and
      differentiated cells against the toxic effects of 1-methyl-4-phenylpyridinium ion
      at the concentration range of 20-40 microM, as assessed by the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The production of
      reactive oxygen species in the mitochondria was suppressed. The cytotoxicity of 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine was unchanged in both actively
      dividing and differentiated cells overexpressing CYP2D6 versus mock-transfected
      controls at concentrations up to 500 microM. These results suggest that the
      lowered enzyme activity of CYP2D6 in individuals termed "poor metabolizers" may
      represent a risk factor from exposure to select neurotoxicants.

PMID- 14686786
TI  - Transcriptomic classification of antitumor agents: application to the analysis of
      the antitumoral effect of SR31747A.
AB  - SR31747A is a sigma ligand that exhibits a potent antitumoral activity on various
      human tumor cell lines both in vitro and in vivo. To understand its mode of
      action, we used DNA microarray technology combined with a new bioinformatic
      approach to identify genes that are modulated by SR31747A in different human
      breast or prostate cancer cell lines. The SR31747A transcriptional signature was
      also compared with that of seven different representative anticancer drugs
      commonly used in the clinic. To this aim, we performed a two-dimensional
      hierarchical clustering analysis of drugs and genes which showed that 1) standard
      molecules with similar mechanism of action clustered together and 2) SR31747A
      does not belong to any previously characterized class of standard anticancer
      drugs. Moreover, we showed that 3) SR31747A mainly exerted its antiproliferative
      effect by inhibiting the expression of genes playing a key role in DNA
      replication and cell cycle progression. Finally, contrasting with other drugs, we
      obtained evidence that 4) SR31747A strongly inhibited the expression of three key
      enzymes of the nucleotide synthesis pathway (i.e., dihydrofolate reductase,
      thymidylate synthase, and thymidine kinase) with the latter shown both at the
      mRNA and protein levels. These results, obtained through a novel molecular
      approach to characterize and compare anticancer agents, showed that SR31747A
      exhibits an original mechanism of action, very likely through unexpected targets
      whose modulations may account for its antitumoral effect.

PMID- 14686787
TI  - Expression of Wnt, Frizzled, sFRP, and DKK genes in adult human pancreas.
AB  - Wnts are important signaling molecules involved in many normal developmental
      processes in the human body as well as some forms of cancer. Nineteen Wnt genes
      are found in the human genome, as well as 10 Wnt receptor genes called Frizzled.
      Two coreceptors called LRP 5 and 6 are critical for Wnt signal transduction. The
      interaction of the Wnts with the receptors is regulated by two classes of
      extracellular Wnt or LRP binding proteins called sFRP and Dickkopf (DKK), which
      modulate Wnt signaling. We have examined the expression of all Wnt family members
      both in the exocrine portion and in isolated islets of adult human pancreas. RT
      PCR analysis of the 1-day cultured exocrine pellet fraction from the islet
      isolation procedure showed that Wnt 2, 2b, 3, 4, 5a, 5b, 7a, 7b, 14, and 15 were
      detectable. All 10 Frizzled (Frz) receptors were expressed but only Frizzled 1,
      2, 4, 5, and 6 strongly. RT-PCR performed on purified human islets revealed that
      Wnt 2b, 3, 4, 5a, 7b, 10a, and 14 and Frz 4, 5, and 6 were the most highly
      expressed. DKK 1, 3, and 4 as well as sFRP 1, 4, and 5 were expressed in the
      exocrine fraction. sFRP 2 and 3 were detectable but only at low levels. In situ
      hybridization for Frz 1-7 showed that expression colocalized with the islets of
      Langerhans. Together the data suggest that active Wnt signaling occurs in adult
      pancreas and is probably important for physiological functions.

PMID- 14686788
TI  - Rapid hepatocyte nuclear translocation of the Forkhead Box M1B (FoxM1B)
      transcription factor caused a transient increase in size of regenerating
      transgenic hepatocytes.
AB  - The Forkhead Box (Fox) proteins are an extensive family of transcription factors
      that shares homology in the winged helix DNA binding domain. Liver regeneration
      studies with the -3 kb transthyretin (TTR) promoter-driven FoxM1B transgenic (TG)
      mice demonstrated that premature hepatocyte nuclear localization of the FoxM1B
      transgene protein at 16 h following partial hepatectomy (PHx) caused an 8-h
      acceleration in the onset of hepatocyte DNA replication (S-phase) and mitosis by
      stimulating earlier expression of cell cycle genes. Whether the FoxM1B transgene
      protein participates in immediate early events during liver regeneration remains
      to be determined. Here, we found that the FoxM1B transgene protein translocated
      to hepatocyte nuclei immediately following PHx, that its nuclear staining
      persisted for the first 6 h after surgery, and that this translocation was
      associated with an increase in size of regenerating TG hepatocytes. However,
      regenerating TTR-FoxM1B liver did not exhibit altered expression of proteins that
      have been implicated in mediating increased cell size, including serum-and
      gucocorticoid-inducible protein kinase (SGK), protein kinase-B/Akt, the tumor
      suppresser gene PTEN (negative regulator of the PI3K/Akt pathway), c-Myc, or
      peroxisome proliferation. Moreover, we demonstrated that hepatocyte nuclear
      translocation of the FoxM1B transgene protein was rapidly induced during the
      hepatic acute phase response, which occurs during the immediate early stages of
      liver regeneration. Analysis of cDNA expression arrays identified a number of
      genes such as immediate early transcription factors (ID-3, Stat3, Nur77), matrix
      metalloproteinase-9 (MMP-9), and several glutathione S-transferase (GST) isoforms
      and stress response genes, whose expression is elevated in regenerating TTR
      FoxM1B TG livers compared with regenerating wild-type (WT) liver. These liver
      regeneration studies demonstrate that hepatocyte nuclear translocation of the
      FoxM1B transgene protein was sustained for the first 6 h after PHx, and was
      associated with transient hypertrophy of regenerating TG hepatocytes and
      increased expression of genes that may enhance hepatocyte proliferation.

PMID- 14686789
TI  - Gene structure, alternate splicing, tissue distribution, cellular localization,
      and developmental expression pattern of mouse deubiquitinating enzyme isoforms
      Usp2-45 and Usp2-69.
AB  - We have identified a novel mouse gene, Usp2, encoding two ubiquitin-specific
      proteases (USPs) due to alternate splicing of 5' exons. Usp2-45 consists of 396
      amino acids (45.2 kDa), while Usp2-69 is 619 amino acids (69.5 kDa). Usp2-69
      results from the splicing of different combinations of untranslated 5' exons (1A,
      1B, 1C) onto exon 1D and the 40-kDa catalytic core (exons 3-13), while Usp2-45
      has exon 2 spliced onto the core. The catalytic core contains the highly
      conserved motifs of the UBP family of deubiquitinating enzymes. We can find no
      evidence for a reported 41-kDa isoform (UBP41) in any sequence databases. Usp2-69
      is able to form a complex with Usp2-45 and with itself. Antibodies raised against
      the catalytic core recognized a 69-kDa protein, but did not detect a 45-kDa
      protein in mouse tissues. Using Northern blot, Western blot, and
      immunohistochemistry, Usp2 expression was observed in many adult and embryonic
      tissues including testis, heart, skeletal muscle, diaphragm, brain, kidney,
      liver, pancreas, lung, and skin. Both Usp2 isoforms were localized to the
      cytoplasm when overexpressed in COS-7 and NIH3T3 cells. The Usp2 expression
      pattern indicates that this protein might be involved in specific processes in
      different types of cells, especially those that are differentiating, and that its
      function is not restricted to a development of a particular organ.

PMID- 14686790
TI  - Gene expression profiling of the hypoxia signaling pathway in hypoxia-inducible
      factor 1alpha null mouse embryonic fibroblasts.
AB  - Hypoxia is defined as a deficiency of oxygen reaching the tissues of the body,
      and it plays a critical role in development and pathological conditions, such as
      cancer. Once tumors outgrow their blood supply, their central portion becomes
      hypoxic and the tumor stimulates angiogenesis through the activation of the
      hypoxia-inducible factors (HIFs). HIFs are transcription factors that are
      regulated in an oxygen-dependent manner by a group of prolyl hydroxylases (known
      as PHDs or HPHs). Our understanding of hypoxia signaling is limited by our
      incomplete knowledge of HIF target genes. cDNA microarrays and a cell line
      lacking a principal HIF protein, HIF1alpha, were used to identify a more complete
      set of hypoxia-regulated genes. The microarrays identified a group of 286 clones
      that were significantly influenced by hypoxia and 54 of these were coordinately
      regulated by cobalt chloride. The expression profile of HIF1alpha -/- cells also
      identified a group of downregulated genes encoding enzymes involved in protecting
      cells from oxidative stress, offering an explanation for the increased
      sensitivity of HIF1alpha -/- cells to agents that promote this type of response.
      The microarray studies confirmed the hypoxia-induced expression of the HIF
      regulating prolyl hydroxylase, PHD2. An analysis of the members of the PHD family
      revealed that they are differentially regulated by cobalt chloride and hypoxia.
      These results suggest that HIF1alpha is the predominant isoform in fibroblasts
      and that it regulates a wide battery of genes critical for normal cellular
      function and survival under various stresses.

PMID- 14686791
TI  - Comprehensive expression profiling of highly homologous 39 hox genes in 26
      different human adult tissues by the modified systematic multiplex RT-pCR method
      reveals tissue-specific expression pattern that suggests an important role of
      chromosomal structure in the regulation of hox gene expression in adult tissues.
AB  - Homeobox genes play a crucial role as molecular address labels in early
      embryogenesis by conferring cell fate and establishing regional identity in
      tissues. Homeobox gene expression is not restricted to the early development, but
      it is also observed in the differentiated cells in adult tissues. To have a
      better understanding of the functionality of homeobox gene expression in adult
      tissues in physiological and pathological phenomena, it is important to determine
      the expression profiles of Hox genes. We established a system to study the
      expression of 39 human Hox genes by the modified Systematic Multiplex RT-PCR
      method. Using this system, we have systematically examined their expression in 26
      different adult tissues. The results showed tissue-specific differential
      expression. They also revealed that the posterior tissues generally express more
      Hox genes than the anterior tissues and that the genes located centrally in the
      Hox Gene Complexes are expressed in more tissues than the genes located at the 5'
      or 3' end of the complexes. Instead of similar expression patterns among
      paralogous genes, we found that several neighboring Hox genes on the same
      chromosomes exhibited similar tissue-specific expression pattern, which may
      suggest that the regulation of Hox gene expression may be more dependent on
      chromosomal structure in adult tissues.

PMID- 14686792
TI  - Effect of bojungikki-tang on lipopolysaccharide-induced cytokine production from
      peripheral blood mononuclear cells of chronic fatigue syndrome patients.
AB  - Bojungikki-tang (BIT) has been widely used to treat patients suffering from
      chronic fatigue syndrome (CFS). However, its effect has not been yet investigated
      experimentally. Based upon the clinical presentation of CFS, we hypothesized that
      cytokines may play a role in the pathogenesis of the disease. We studied the
      effect of BIT on lipopolysaccharide (LPS)-induced various cytokines production in
      peripheral blood mononuclear cells (PBMC) of CFS patients. Bojungikki-tang (1
      mg/mL) significantly inhibited LPS-induced tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta1 production by
      63.55% +/- 0.19%, 55.06% +/- 0.27%, 48.23% +/- 0.48%, 54.09% +/- 0.76%,
      respectively (P < 0.05). Bojungikki-tang showed a slightly lower inhibitory
      effect of LPS-induced Interferon (IFN)-gamma production. These results suggest
      that BIT may be useful in treating fatigue associated with chronic diseases.

PMID- 14686793
TI  - The effect of Jeo Dang-Tang on cytokines production in the patients with cerebral
      infarction.
AB  - The herbal formulation "Jeo Dang-Tang" (JDT) has long been used for various
      cerebrovascular diseases. However, very little has scientific investigation been
      carried out. The aim of the present study is to investigate the effect of JDT on
      the production of various cytokines in the patients with cerebral infarction
      (CI). Peripheral blood mononuclear cells (PBMC) obtained from the patients with
      CI were cultured for 24h in the presence or absence of lipopolysaccharide (LPS)
      or phytohemagglutinin (PHA). The amount of interleukin (IL)-4, IL-10 and
      transforming growth factor (TGF)-1beta, in culture supernatant, was significantly
      increased in the JDT, LPS or PHA treated cells compared to unstimulated cells (P
      < 0.05). We also show that increased IL-4, and IL-10 level by LPS or PHA was
      significantly inhibited by JDT in a dose-dependent manner. Maximal inhibition
      rate of IL-4 and IL-10 production by JDT was 45 +/- 2% and 51 +/- 5% for LPS
      stimulated cell and 41.5 +/- 3% and 70.8 +/- 2% for PHA-stimulated cells,
      respectively (P < 0.05). On the other hand, JDT significantly increased the LPS
      or PHA-induced TGF-beta1 production (P < 0.05). These data suggest that JDT has a
      regulatory effect on the cytokines production, which might explain its beneficial
      effect in the treatment of CI.

PMID- 14686794
TI  - Thymopoiesis following chronic blockade of beta-adrenoceptors.
AB  - The present study was undertaken in order to further clarify putative role of the
      adrenergic innervation in the regulation of the intrathymic T-cell maturation.
      For this purpose adult male DA rats were subjected to either 4-day- or 16-day
      long propranolol treatment (0.40 mg propranolol/100 g/day, s.c.) and the
      expression of CD4/8/TCRalphabeta on thymocytes, as well as thymocyte
      proliferative and apoptotic index, was assessed in these animals by flow
      cytometric analysis. Propranolol treatment, in spite of duration, increased both
      the thymocyte proliferative and apoptotic index (vs. respective vehicle-treated
      controls). In 4-day-treated animals the thymus cellularity and thymus weight
      remained unaltered, while in 16-day-treated rats the values of both of these
      parameters were reduced (since increase in the thymocyte apoptotic index overcame
      that in the proliferative index). The treatments of both durations affected the
      thymocyte phenotypic profile in a similar pattern, but the changes were more
      pronounced in rats exposed to the treatment of longer duration. The relative
      proportion of the least mature CD4-8- double negative (DN) TCRalphabeta- cells
      was increased, those of thymocytes at distinct differentiational stages on the
      transitional route to the CD4+8+ double positive (DP) TCRalphabetalow stage
      decreased (all subsets of TCRalphabeta- in both groups of rats, and those with
      low expression of TCRalphabeta in rats subjected to 16-day-long treatment) or
      unaltered (all subsets of TCRalphabetalow cells in 4-day-treated rats).
      Furthermore, the percentage of CD4+8+ DP TCRalphabetalow cells was significantly
      elevated, as well as those of the most mature CD4+8- TCRalphabetahigh and CD4-8+
      TCRalphabetahigh cells (the increase in the percentage of former was much more
      conspicuous than that of the latter), while the relative proportion of their
      direct detectable precursors (CD4+8+ DP TCRalphabetahigh) was reduced. Thus, the
      present study: i) further supports notion of pharmacological manipulation of
      adrenergic action as an efficient means in modulation of the T-cell development,
      and hence T-cell-dependent immune response, and ii) provides more specific
      insight into T-cell maturation sequence point/s particularly sensitive to beta
      adrenoceptor ligand action.

PMID- 14686795
TI  - Eyedrop-induced allergy: clinical evaluation and diagnostic protocol.
AB  - BACKGROUND: In the last few years, adverse reactions to mydriatic eyedrops have
      been investigated. However, is not still available a standardized protocol,
      capable of identify the pathogenetic mechanism. In the light of these findings we
      have evaluated the reliability of a protocol with well established concentration
      of specific allergens. METHODS: The diagnostic method includes the application of
      patch test series Gruppo Italiano Ricerca Dermatiti da Contatto e Ambientali
      (GIRDCA), medicaments, corticosteroids, local anesthetics, main eyedrops'
      excipients, pure active principles and extemporaneous preparations with mydriatic
      eyewashes. At the same time, skin prick test with a solution of atropine sulfate
      at 1 per thousand and an intradermal test with injection of atropine at 0.01 per
      thousand were carried out. RESULTS: After patch tests were removed, we detected
      seven positiveness to the phenylephrine, two to the benzalkonium chloride, one to
      thiomersal, one to the ethylendiamine and one to the atropine sulfate 1 per
      thousand. With intradermal tests we obtained three positiveness in patients who
      reported adverse reactions to atropine. CONCLUSIONS: Our results show that
      phenylephrine is frequently responsible for allergic conjunctivitis (53.8%). In
      the case of atropine, even though the limited number of patients suggests to
      perform more extensive studies, it emerges that our diagnostic protocol is safe
      and might be able to screen allergic reactions in the field of ophthalmopathies.

PMID- 14686796
TI  - Augmentation by 2-mercaptoethanol of in vitro anti-TNP antibody production
      induced by butyrate plus IL-2 in murine splenic B cells.
AB  - We previously reported that anti-trinitrophenyl (TNP) antibody production in
      murine splenic B cells stimulated with TNP-lipopolysaccharide in vitro was
      promoted by sodium butyrate (NaBu) in an IL-2-dependent manner. In the present
      study, we found that the effect of NaBu plus IL-2 was markedly augmented by 2
      mercaptoethanol (2-ME), which showed a slight or null effect on the response of
      untreated, IL-2-treated or NaBu-treated B cells, as assessed by both anti-TNP
      plaque-forming cell assay and anti-TNP IgM ELISA. Other thiol compounds such as
      dithiothreitol, cysteamine and reduced glutathione (GSH) also had this activity.
      2-ME enhanced the anti-TNP antibody production induced by other short-chain fatty
      acids with three to five carbon atoms plus IL-2. The proliferation of B cells was
      significantly inhibited by NaBu or NaBu plus IL-2, and the proliferation was
      completely restored by the simultaneous addition of 2-ME. These results
      demonstrate that 2-ME markedly enhanced anti-TNP antibody production in murine B
      cells induced by NaBu plus IL-2 and suggest that the effect of 2-ME is at least
      partly due to its blocking activity of the growth-inhibitory action of NaBu.

PMID- 14686797
TI  - Enhancement of the humoral immune response by Echinacea purpurea in female Swiss
      mice.
AB  - Various preparations of the plant Echinacea purpurea have been investigated for
      their potential to enhance immune function, primarily through activation of
      innate immune responses. Few studies have examined the potential for enhancement
      of humoral immunity. Using female Swiss mice we administered a volumetric dose of
      a glycerine extract of E. purpurea by oral gavage, to evaluate effects on the IgM
      specific antibody forming cell (AFC) response. Four days of treatment following
      immunization with sheep red blood cells (SRBC) produced a significant enhancement
      over naive controls at doses of 0.4 and 0.8 mL/kg/day. A few clinical trials and
      anecdotal reports have suggested that the greatest efficacy for E. purpurea
      occurs in acute use following onset of illness. A time course study, using the
      time of SRBC immunization to mimic the onset of illness, examined the effects of
      8 and 4 days of E. purpurea treatment at 0.6 mL/kg/day. Only in the 4-day
      administration, with dosing beginning 1 hour after SRBC immunization, was there
      an observed enhancement of the antibody forming cell response. This supports the
      acute use of E. purpurea as suggested by anecdotal reports, and demonstrates the
      potential for enhancement of humoral immune responses as well as innate immune
      responses.

PMID- 14686798
TI  - The antiplatelet activity of Danggijakyaksan by inhibition of phospholipase C.
AB  - We investigated the effects of the traditional Korean prescription,
      Danggijakyaksan (DJS) on antiplatelet activity in human platelet suspensions. The
      effect of oriental medicinal prescriptions, Danggijakyaksan consisting of 6
      herbes of Paeoniae Radix (2 g), Poria Cocos (1.33 g), Angelicae Sinensis Radix (1
      g), Cnidii Rhizoma (1 g), Atractylodis Macrocephalae Rhizoma (1.33 g) and
      Alismatis Rhizoma (1.66 g), was studied. In this study, the mechanism involved in
      the antiplatelet activity of DJS in human platelet suspensions was investigated.
      Danggijakyaksan did not significantly affect the thromboxane synthetase activity
      of aspirin-treated platelet microsomes and DJS (20 and 40 microg/mL)
      significantly inhibited [3H]arachidonic acid (AA) released in collagen-activated
      platelets but not in unactivated-platelets. Nitric oxide (NO) production in human
      platelets was measured by a chemiluminesence detection method in this study.
      Danggijakyaksan did not significantly affect nitrate production in collagen (10
      microg/mL)-induced human platelet aggregation. On the other hand, various
      concentrations of DJS (10, 20, and 40 microg/mL) dose-dependently inhibited
      [3H]inositol monophosphate (IP) formation stimulated by collagen (10 microg/mL)
      in [3H]myoinositolloaded platelets at different incubation times (1, 2, 3, and 5
      min). It is concluded that the antiplatelet activity of DJS may possibly be due
      to the inhibition of phospholipase C activity, leading to reduced
      phosphoinositide breakdown, followed by the inhibition of thromboxane A2
      formation, and then inhibition of [Ca2+]i mobilization of platelet aggregation
      stimulated by agonists.

PMID- 14686799
TI  - Swertia chirayita mediated modulation of interleukin-1beta, interleukin-6,
      interleukin-10, interferon-gamma, and tumor necrosis factor-alpha in arthritic
      mice.
AB  - The effect of aqueous extract of Swertia chirayita stem on the pro- and anti
      inflammatory cytokines balance in primary joint synovium of adjuvant-induced
      arthritic mice has been studied. The level of pro-inflammatory cytokines was
      found elevated in the joint synovium of arthritic mice in comparison to normal
      joints. Administration of S. chirayita extract in varying doses through the oral
      route did not modulate the proinflammatory cytokines on day 2. In contrast, by
      day 12, a dose dependent (0, 11.86 and 23.72 mg/kg body weight) reduction of
      tumor necrosis factor-alpha (INF-alpha) interleukin-1beta, (IL-beta) and
      interferon-gamma, (IFN-gamma) and elevation of Interleukin-10 (IL-10) was
      observed in the joint homogenates of arthritic mice. Interleukin-6 (IL-6) was not
      down regulated in joint homogenate of arthritic mice at the dose 11.86 mg/kg but
      at higher doses (23.72 and 35.58 mg/kg) significant reduction was observed. The
      aqueous extract was found to possess two polar compounds, amerogentin and
      mangiferin but was devoid of swerchirin, chiratol, methyl swetianin, and
      swertanone. Mangiferin has been reported to possess potent anti-inflammatory
      property and we presume its presence in the aqueous extract of S. chirayita is
      responsible for reducing TNF-alpha, IL-1beta, IL-6, and IFN-gamma and/or
      elevating IL-10 in the joint homogenates of arthritic mice on day 12. This study
      will help in our understanding of the mechanism of anti-inflammatory action of S.
      chirayita in the light of proinflammatory and anti-inflammatory cytokine balance.

PMID- 14686800
TI  - Hepatoprotective effect of baicalin, a major flavone from Scutellaria radix, on
      acetaminophen-induced liver injury in mice.
AB  - The protective effects of baicalin (BA), a major flavone from Scutellaria radix,
      on acetaminophen (AP)-induced hepatotoxicity and the possible mechanism(s) of its
      protective action were investigated in mice. Treatment with BA (300 mg/kg, p.o.)
      0.5 h after AP administration significantly prevented an increase in plasma
      alanine aminotransferase and aspartate aminotransferase activities and AP-induced
      hepatic necrosis, and also reduced AP-induced mortality from 43% to 0%. In
      addition, oral treatment with BA significantly prevented AP-induced depletion of
      glutathione (GSH) contents. However, BA treatment, by itself, did not affect
      hepatic GSH contents. The effect of BA on the cytochrome P450 2E1 (CYP2E1), the
      major isozyme involved in AP bioactivation, was investigated. Oral treatment of
      mice with BA resulted in a significant decrease in AP-induced CYP2E1 activity
      together with its inhibition of AP-induced CYP2EI expression. These results show
      that the hepatoprotective effects of BA against AP overdose may be due to its
      ability to block the bioactivation of AP by inhibiting CYP2E1 expression.

PMID- 14686801
TI  - Saliva secretory IgA antibodies against molds and mycotoxins in patients exposed
      to toxigenic fungi.
AB  - Upper respiratory exposure to different environmental antigens results first in
      the activation of mucosal immunity and production of IgA antibodies in different
      secretions including saliva. Despite this there is no study, which addresses
      secretory antibodies against molds and mycotoxins. The purpose of this study was
      to evaluate mold-specific salivary IgA in individuals exposed to molds and
      mycotoxins in a water-damaged building environment. Saliva IgA antibody levels
      against seven different molds and two mycotoxins were studied in 40 patients
      exposed to molds and in 40 control subjects. Mold-exposed patients showed
      significantly higher levels of salivary IgA antibodies against one or more mold
      species. A majority of patients with high IgA antibodies against molds exhibited
      elevation in salivary IgA against mycotoxins, as well. These IgA antibodies
      against molds and mycotoxins are specific, since using molds and mycotoxins in
      immune absorption could reduce antibody levels, significantly. Detection of high
      counts of molds in water-damaged buildings, strongly suggests the existence of a
      reservoir of mold spores in the environment. This viable microbial activity with
      specific mold and mycotoxin IgA in saliva may assist in the diagnosis of mold
      exposure. Whether mold and mycotoxin specific IgA antibodies detected in saliva
      are indicative of the role of IgA antibodies in the late phase of type-1
      hypersensitivity reaction or in type-2 and type-3 delayed sensitivities is a
      matter that warrants further investigation.

PMID- 14686802
TI  - Fructus Benincasae Recens extract prevents cytokine-induced nitric oxide
      formation and cytotoxicity of RINm5F cells.
AB  - Cytokines produced by immune cells infiltrating pancreatic islets are important
      mediators of beta-cell destruction in insulin-dependent diabetes mellitus. In
      this study, the effects of Fructus Benincasae Recens (FBR) extract on cytokine
      induced beta-cell dysfunction were examined. Fructus Benincasae Recens extract
      completely protected interleukin-1beta (IL-1beta) and interferon-gamma (IFN
      gamma)-mediated cytotoxicity in rat insulinoma cell line (RINm5F). Incubation
      with FBR extract resulted in a significant reduction of IL-1beta and IFN-gamma
      induced nitric oxide (NO) production, a finding that correlated well with reduced
      levels of the inducible form of NO synthase (iNOS) mRNA and protein. The
      molecular mechanism by which FBR extract inhibited iNOS gene expression appeared
      to involve the inhibition of NF-kappaB activation. Our results revealed the
      possible therapeutic value of FBR extract for the prevention of diabetes mellitus
      progression.

PMID- 14686803
TI  - Effects of testosterone undecanoate as a male contraceptive candidate on rat
      immunological features.
AB  - Testosterone undecanoate (TU) is under phase III clinical trial as a hormonal
      male contraceptive in China. Sex hormones can modulate the immune system. Female
      hormonal contraceptives may affect SIV/HIV-1 transmission. To evaluate the safety
      of TU and to understand whether long-term use of TU for a male contraceptive
      affects users' immunological features, adult male rats were treated for a 32-week
      TU-treated phase at the dose of 20 mg TU/kg body weight and a 24-week recovery
      phase. The reproductive and immunological parameters of 4-6 rats in each subgroup
      were examined at the stated time point. The mean sperm count and viability in the
      treated rats were significantly suppressed (p < 0.01). In the TU-treated group:
      the mean blood leukocyte and lymphocyte counts; the proliferation indexes of T
      cells from peripheral blood mononuclear cells (PBMC) and spleen; and, of B cells
      from spleen, as well as the mean counts of blood T, NK, and B cells decreased in
      comparison with those of control group. These decreases were not significant (p >
      0.01). Similarly, the mean serum IgM, IgG, and IgA levels and complement activity
      in TU-treated rats were lower than those in control group (p > 0.01), and the
      changes in the antibody levels of the examined genital secretions were not
      significant (p > 0.01). The changes in the thickness of urethra epithelium, and
      in secretory component (SC) expression in genitals were not observed in the
      treated group. These results demonstrated that long-term supraphysiological TU
      injection did not obviously affect the examined rat immunological parameters.

PMID- 14686804
TI  - A proline-rich polypeptide complex (PRP) from ovine colostrum. Studies on the
      effect of PRP on nitric oxide (NO) production induced by LPS in THP-1 cells.
AB  - A proline-rich polypeptide complex (PRP) isolated from ovine colostrum shows
      immunoregulatory activity. Similar activity was observed when PRP was replaced
      with a nonapeptide (NP) isolated from chymotryptic digest of PRP. The polypeptide
      complex also shows procognitive activity. In the form of orally administered
      tablets called Colostrinin, containing 100 microg of PRP, it improves the outcome
      of Alzheimer's disease (AD) patients. The mechanism of action of PRP/Colostrinin
      in AD is not yet clarified. Microglial cells involvement in AD has been related
      to amyloid beta (Abeta) internalization, the release of inflammatory cytokines,
      overproduction of nitrogen oxide (NO) and superoxide anion (O2-), and the
      development of neuritic plaques. It has been previously found in our laboratory
      that PRP regulates the secretion of an array of cytokines. It also was shown, in
      preliminary experiments using human blood cells and murine macrophages, that PRP
      inhibits production of NO and O2- induced by LPS. In the present work, to study
      the effect of PRP and NP on the release of NO and O2-induced by LPS we applied
      THP-1 cells. The human monocyte/macrophage THP-1 cell line has been widely used
      as a model of human microglial cells. The results obtained showed that THP-1
      cells release NO when activated with LPS. However, neither PRP nor NP induced
      production of NO. Although the nonapeptide, at higher concentration (100
      microg/mL), showed an inhibitory activity on the release of NO induced by LPS, no
      inhibition was observed when PRP was used. THP-1 cells treated with LPS, PRP or
      NP did not release O2-.

PMID- 14686805
TI  - A toxicokinetic study of nickel-induced immunosuppression in rats.
AB  - The aim of the present study was to investigate dose- and time-dependent effects
      of NiCl2 on T-lymphocyte and macrophage-derived cytokine production in rats.
      Moreover we have determined the concentrations of nickel in the plasma that are
      required to elicit alterations in T-lymphocyte and macrophage function. NiCl2
      suppressed T-lymphocyte proliferation and Th1 (IFN-gamma) and Th2 (IL-10)
      cytokine production in a dose- and time-dependent fashion. In addition, NiCl2
      inhibited production of the pro-inflammatory cytokine TNF-alpha and increased
      production of the anti-inflammatory cytokine IL-10 from lipopolysaccharide (LPS)
      stimulated cultures. We have determined that the minimal plasma concentrations of
      nickel required to provoke immunosuppression are in the range 209-585 ng/mL. In
      the time-course study NiCl2 (3.3 mg/kg) provoked immunological changes that were
      maximal 1 h following administration, and some of these changes persisted for up
      to 24 h post administration. Overall these data clearly demonstrate that NiCl2
      suppresses T-cell function and promotes an immunosuppressive macrophage phenotype
      in rats. This study also indicates that measuring T-cell proliferation is as
      sensitive a marker of NiCl2-induced immunotoxicity as measuring T-cell or
      macrophage cytokine production. Co-measurement of circulating nickel
      concentrations and immune parameters yields valuable information with regard to
      the potency of nickel to alter immune function in vivo. These data also suggest
      that quite a large quantity of nickel needs to reach the systemic circulation
      before any adverse effects on immune function are observed.

PMID- 14686806
TI  - Treatment outcome in endodontics: the Toronto Study. Phase 1: initial treatment.
AB  - This study assessed the 4- to 6-yr outcome of initial endodontic treatment during
      Phase 1 of the "Toronto Study" project. A total of 450 teeth were treated,
      alternating the "Schilder" technique and step-back with lateral condensation, and
      examined clinically and radiographically by an independent examiner. Apical
      periodontitis was recorded as absent (periapical index < 3) or present
      (periapical index > or = 3) and outcome dichotomized as "healed" (no apical
      periodontitis, no signs or symptoms) or "disease." Univariate, bivariate, and
      multivariate analyses were performed (p = 0.05) on 120 examined teeth. The
      "healed" rate (81% overall) was significantly higher for teeth treated without
      apical periodontitis (92%) than with apical periodontitis (74%). Several other
      factors were associated with healing rate differential of 10% or higher, but no
      statistical significance. This study confirmed apical periodontitis as the main
      prognostic factor in initial endodontic treatment. Continuation of the project
      will allow assessment of other prognostic factors with better power.

PMID- 14686807
TI  - Identification of spirochetes (treponemes) in endodontic infections.
AB  - The purpose of this study was to determine the prevalence of spirochetes in
      asymptomatic infected root canals and in endodontic abscesses/cellulitis. Aseptic
      clinical samples were collected using paper points from 54 infected root canals
      and from aspirates of 84 abscesses/cellulitis. Oligonucleotide primers were
      produced for PCR identification of Treponema vincentii, T. pectinovorum, T.
      medium, T. amylovorum, T. denticola, T. maltophilum, and T. socranskii. PCR
      detected spirochetes in 51 of 84 (60.7%) samples from abscesses/cellulitis and in
      20 of 54 (37.0%) samples from asymptomatic infected root canals. T. socranskii
      was the most frequently detected (44.9%), followed by T. maltophilum (29.7%), T.
      denticola (28.9%), T. pectinovorum (13.7%), and T. vincentii (5.1%). The number
      of treponema species detected ranged from 1 to 5 species per sample. The mean
      numbers of species detected were 2.3 in abscesses/cellulitis and 2.6 in infected
      root canals. Significant association among species was found between T.
      maltophilum and T. socranskii, as well as between T. maltophilum and T. denticola
      by determining the odds ratio (> 2.0).

PMID- 14686808
TI  - Prevalence of odontogenic sinus tracts in patients referred for endodontic
      therapy.
AB  - The purpose of this study was to determine the prevalence of odontogenic sinus
      tracts in patients referred for endodontic therapy. Charts of 330 patients (393
      permanent teeth) endodontically treated during a 10-month period were reviewed
      and data was collected. Among the 393 permanent teeth there were a total of 160
      teeth with preoperative status of periradicular inflammation. Of 160 teeth with
      preoperative status of periradicular inflammation, 29 teeth (18.1%) had an
      odontogenic sinus tract, which correlates to almost one in five teeth with
      periradicular inflammation having a sinus tract.

PMID- 14686809
TI  - Validity of a three-dimensional public-domain system for contemporary endodontic
      research.
AB  - The purpose of this study was to evaluate the limits and benefits of a
      visualization system based on public-domain software for contemporary three
      dimensional (3-D) endodontic research purposes. Three-dimensional bio-models of
      six human teeth and of one bone-implant specimen were generated using cross
      sectional imaging. To evaluate the overall performance in processing large data
      sets and in reproducing accurate 3-D morphology, slices with a thickness varying
      from 100 microm to 10 microm were cut. Auto-outlining and segmenting techniques
      were tested. The 3-D bio-models represented in accurate detail the different
      morphological aspects of the specimen. Voxel volumes of 0.116 x 10(-5) mm3 could
      be realized and were only restricted by the computer hardware limitations. The
      system is not limited to dental hard tissues. Hypomineralized material and soft
      tissues as well as bone- and allogeneic-implant material could be visualized. The
      method presented is valid and meets current requirements applying to endodontic
      research. The broad-based use of high-quality, public-domain software and the
      resulting exchange of experience help to manage resources and may contribute to
      enhancing the in-process quality of research.

PMID- 14686810
TI  - Incidence of endodontic treatment: a 48-month prospective study.
AB  - The purpose of this study was to determine the incidence of endodontic services
      provided to participants in a longitudinal cohort study. The "Florida Dental Care
      Study" was a prospective cohort study using a representative baseline sample of
      873 dentate adults. An in-person interview and clinical dental exam were
      conducted at baseline, 24, and 48 months after baseline, with telephone
      interviews every 6 months between those times. Dental record information was
      abstracted afterward. Thirteen percent of participants received at least one
      endodontic procedure after baseline. Endodontic services constituted
      approximately 2% of all dental procedures performed. Conventional root canal
      therapy comprised 94% of the endodontic services and was approximately evenly
      distributed among anterior teeth, premolars, and molars. Retreatment and
      apicoectomy each accounted for 3% of the endodontic procedures. The most common
      self-reported reasons for the dental visit in which a root canal occurred were
      "toothache," "abscess," and "dental sensitivity." A significant percentage of
      persons received some type of endodontic treatment in this diverse adult sample.
      Dental abscesses or toothaches were the main reason(s) for endodontic treatment,
      but not all persons with these conditions during follow-up sought dental
      treatment of any variety.

PMID- 14686811
TI  - Effect of dexamethasone on root resorption after delayed replantation of rat
      tooth.
AB  - The purpose of this study was to evaluate the effect of dexamethasone after
      delayed tooth replantation with specific regard to root resorption and ankylosis.
      In addition, the study was planned to elucidate further the usefulness of the
      model. Fifty-two maxillary first molar teeth were extracted from 26 Sprague
      Dawley white female rats fed 0.4% beta-aminoproprionitrile for 3 days to
      facilitate the extraction. After extraction, the mesiobuccal root canals were
      endodontically treated under a microscope to prevent subsequent inflammatory
      resorption of pulpal origin and were assigned to three groups. Teeth in group 1,
      the dexamethasone group (n = 22), were demineralized in citric acid (1 min),
      washed, soaked in 1000 nM dexamethasone solution (3 min), air-dried, and
      replanted in the original sockets. Total extraoral treatment time for each tooth
      was controlled to 30 min. Teeth in group 2, the dried-only group (n = 22), were
      air-dried for 30 min after obturation without any surface treatment and
      replanted. Teeth in group 3, the immediate group (n = 8), were extracted, not
      root-filled and replanted immediately into their sockets. All experimental
      animals were killed at 3 weeks after replantation and evaluated histologically.
      Forty-three of the 52 teeth were available for histological interpretation. They
      consisted of six immediate, 18 dried-only, and 19 dexamethasone-treated teeth.
      The degree of progressive root resorption was significantly less in the
      dexamethasone-treated group than in the dried-only group (p < 0.05). The
      dexamethasone-treated group exhibited significantly more bone ankylosis than the
      dried-only group (p < 0.05). These results indicate that the topical use of
      dexamethasone may be of value in reducing the degree or rate of progressive root
      resorption secondary to traumatic avulsion and that the rat is a reasonable model
      for tooth replantation.

PMID- 14686812
TI  - Mineral trioxide aggregate (MTA) solubility and porosity with different water-to
      powder ratios.
AB  - This study tested mineral trioxide aggregate (MTA) solubility and porosity with
      different water-to-powder proportions. The study also determined the chemical
      composition of the salts dissolved by MTA. Four sets of specimens using the
      following water-to-powder proportions were prepared: 0.26, 0.28, 0.30, and 0.33
      grams of water per gram of cement. The latter is the ratio recommended by the
      manufacturer. It was determined that the degree of solubility and porosity
      increased as the water-to-powder ratio increased. Significant differences were
      found among the sets of specimens. The chemical analyses of the salts dissolved
      by MTA in the water identified the presence of calcium as the main chemical
      compound. The pH level of the solution was highly alkaline, ranging between 11.94
      and 11.99. It can be stated that the calcium found in the solution should be in
      its hydroxide state at this high pH level. This ability to release calcium
      hydroxide could be of clinical significance because it could be related to the
      proven capacity of MTA to induce mineralization.

PMID- 14686813
TI  - Effect of MTAD on the bond strength to enamel and dentin.
AB  - The purpose of this study was to compare the effect of MTAD (a mixture of a
      tetracycline isomer [doxycycline], an acid [citric acid], and a detergent [Tween
      80]) and phosphoric acid on the bond strength to enamel and dentin using a
      conventional OptiBond Solo Plus dentin adhesive system. One hundred flat surfaces
      (50 enamel/50 dentin) were prepared for bonding. Specimens were embedded in
      acrylic with the flat surface exposed. One of the following surface treatments
      was applied before bonding composite with Optibond Solo Plus (Kerr Corp): 1 min
      NaOCl/1 min EDTA; 1 min NaOCl/1 min MTAD; 30 s etch with H3PO4 (positive
      control), 2 min saline (negative control), or 20 min NaOCl/5 min MTAD (clinical
      protocol for MTAD). Shear bond strength was tested 30 min after bonding. Data
      were analyzed using a one-way ANOVA followed by the Student-Newman-Keuls multiple
      comparison method. Surface pretreatment with acid etch resulted in the greatest
      enamel bond strengths (p < 0.05). All surface pretreatments were superior to
      saline for dentinal bonding (p < 0.05). On the basis of our findings, it appears
      that teeth endodontically treated with the MTAD protocol for clinical use (20 min
      1.3% NaOCl/5 min MTAD) may not need any additional dentin conditioning before the
      application of the dental adhesive.

PMID- 14686814
TI  - Ca2+ diffusion through dentin of Ca(OH)2 associated with seven different
      vehicles.
AB  - This investigation measured the diffusion of Ca2+ through dentin by using Ca(OH)2
      associated with various vehicles. After mechanical preparation and removal of
      smear layer, 41 human premolar teeth were stored individually in flasks
      containing 800 ml of ultra-pure deionized water for 2855 h. The Ca2+
      concentration was measured by atomic absorption spectrophotometry as a function
      of time. These measurements were divided into two phases: dissolution, to check
      the loss of Ca2+ from the tooth structure itself, for which all canals were kept
      empty and open in the absence of medication for 1168 h, and diffusion, in which
      the specimens were divided into 10 groups (3 control groups: group 1 = water
      control, group 2 = sealing control, and group 3 = open canal dissolution control;
      7 experimental groups in which the whose canals were filled with Ca(OH)2 paste
      associated with the following vehicles: group 4 = saline; group 5 = polyethylene
      glycol (Calen); group 6 = glycerin and camphorated parachlorophenol group 7 =
      camphorated paramonochlorophenol; group 8 = glycerin; group 9 = glycerin and
      tricresol formaldehyde (TCF); and group 10 = anesthetic solution. This phase
      lasted 1687 h. A total of 1058 measurements of Ca2+ were made. Regression
      analysis was used for statistical evaluation. We concluded that diffusion
      occurred differently for each group: the medications used in the root canals
      interacted with the dentinal structure or among themselves; the medication coated
      the dentinal tubule, facilitating the diffusion of Ca2+ into the external part of
      the root.

PMID- 14686815
TI  - Evaluation of antifungal activity of mineral trioxide aggregate.
AB  - The purpose of this investigation was to study, in vitro, the antifungal effect
      of mineral trioxide aggregate (MTA) using a tube-dilution test. MTA was tested
      freshly mixed and after 24 h set on Candida albicans. The tested MTA was
      incubated with C. albicans for 1 h, 24 h, and 3 days. Results showed that the
      freshly mixed MTA was effective in killing the tested fungi after 1 day of
      contact, whereas the 24-h set MTA was effective after 3 days of incubation. It
      was concluded that MTA (freshly mixed and 24-h set) was effective against C.
      albicans.

PMID- 14686816
TI  - Comparison of spreader penetration during lateral compaction of .04 and .02
      tapered gutta-percha.
AB  - The purpose of this study was to compare the initial penetration depth of fine
      fine nickel-titanium (NiTi) and fine-fine stainless-steel (SS) spreaders during
      lateral compaction of .02 or .04 tapered master gutta-percha cones and to
      evaluate the effect of increasing canal curvature on penetration depth. Fifty-one
      root canals were instrumented to a standardized size and grouped by degree of
      curvature for comparison. Our results showed that NiTi spreaders penetrated to a
      significantly greater depth than SS spreaders using .02 tapered gutta-percha in
      canal curvatures greater than 20 degrees and when using .04 tapered gutta-percha
      regardless of canal curvature. No significant difference occurred between NiTi
      and SS-spreader penetration using .02 tapered gutta-percha in canal curvatures of
      0 to 20 degrees (p > 0.05). Both NiTi and SS spreaders penetrated to a greater
      depth as canal curvatures increased to greater than 20 degrees (p < 0.05). Both
      NiTi and SS spreaders penetrated to a shallower depth with .04 tapered gutta
      percha compared with .02 tapered gutta-percha (p < 0.0001).

PMID- 14686817
TI  - Intracanal distribution patterns of sealers after lateral condensation.
AB  - The purpose of this study was to examine coverage patterns of sealer on canal
      walls and between gutta-percha cones after lateral condensation. Ninety extracted
      teeth with single canals were evenly and randomly divided into three sealer
      groups (Roth's, Sealapex, AH 26). Canals were cleaned and shaped, then coated
      with one of the three sealers followed by lateral condensation of gutta-percha.
      The teeth were placed into 100% humidity at 37 degrees C. After 4 months the
      roots were notched and fractured longitudinally and the dentin lifted to expose
      the gutta-percha sealer and dentin walls. Qualitative assessment was in the
      apical and coronal as to the amount and the pattern of sealer coverage. Coverage
      was categorized by the amount and location as follows: (a) no sealer; (b) slight
      partial; (c) moderate-partial; or (d) complete coverage. Sealer was frequently
      absent between gutta-percha cones and the canal wall and at times absent between
      cones, with a general moderate-partial coverage. No sealer group demonstrated
      complete coverage; however, AH 26 showed more consistent moderate-partial
      distribution. Coverage was better in the coronal. In conclusion, none of the
      three sealers showed a continuous layer between the primary gutta-percha obturant
      and the canal wall or in spaces between cones.

PMID- 14686818
TI  - Interaction between sealers and gutta-percha cones.
AB  - Clinical observations seem to indicate that some gutta-percha cones are softened
      by contact with sealers. The purpose of the study was to verify whether an
      interaction existed between some sealers and different brands of gutta-percha
      cones. Because previous studies have indicated that the differences between
      brands of gutta-percha are magnified by heat, thermatic compaction was used in
      conjunction with a model of a root-canal preparation with lateral canals. Three
      brands of cones (Kerr, UDM, Beldent) were tested with three types of endodontic
      sealers (AH 26, Apexit, Roth's). A group without sealer served as a control. The
      length of flow into the lateral canals was measured for each combination and
      analyzed by two-way ANOVA. A highly significant difference was found, confirming
      the hypothesis that an interaction between sealer and cones is present in some
      combinations. It was not possible to ascribe a trend of greater effect to a
      certain sealer, but Roth's 811 had the least effect on flow.

PMID- 14686819
TI  - Fracture resistance of endodontically treated premolars restored with ormocer and
      packable composite.
AB  - In this study, mesiodistocclusal (MOD) cavity preparations of endodontically
      treated maxillary premolars that were enlarged to size #50 were restored using
      three restorative materials (one ormocer, one packable composite, and one high
      copper amalgam) and two application techniques (with or without coronal radicular
      technique). Copper rings were filled with self-curing polymethylmethacrylate
      resin and the teeth were placed into resin up to the level of the CEJ. The teeth
      were grouped according to the restorative material and technique, mounted in a
      Universal Testing Machine, and the buccal walls subjected to a slowly increasing
      compressive force until fracture occurred. The force of fracture of the walls of
      each tooth was recorded and the results in the various groups compared. The group
      restored with packable composite without radicular extension showed the highest
      resistance to fracture (p < 0.05). Both groups restored with amalgam were
      significantly weaker than all the other groups (p < 0.05).

PMID- 14686820
TI  - Extraoral sinus tract misdiagnosed as an endodontic lesion.
AB  - The extraoral sinus tract may occur as a result of an inflammatory process
      associated with a necrotic pulp. However, several non-odontogenic disorders may
      also produce an extraoral sinus tract. Thus, the differential diagnosis of this
      clinical finding is of paramount importance in providing appropriate clinical
      care because misdiagnosis of this condition may result in healing failure or
      unnecessary treatment. This case report of a 19-yr-old male patient describes an
      extraoral cutaneous sinus tract misdiagnosed as an endodontic lesion.
      Consequently, the patient underwent unnecessary exploratory procedures and
      antibiotic therapy. Identification of the inflammatory source of the lesion and
      removal of the affected tissue led to tissue healing.

PMID- 14686821
TI  - Why are we doing so many surveys?

PMID- 14686822
TI  - Digital imaging and video: principles and applications.
AB  - Digital imaging has provided orthopaedic surgeons with new, powerful tools that
      offer a multitude of applications. Already integral to several common medical
      devices, digital images can be used for case documentation and presentation as
      well as for diagnostic and surgical patient care information. Educational
      presentation has been transformed by the use of computers and digital projectors.
      Understanding the basic foundations of digital imaging technology is important
      for effectively creating digital images, videos, and presentations.

PMID- 14686823
TI  - Management of scaphoid nonunions.
AB  - Scaphoid nonunions result in a predictable pattern of wrist arthrosis. To
      minimize the incidence of arthrosis, the goal of treatment should be
      consolidation of the fracture with the scaphoid in anatomic alignment. Computed
      tomography and magnetic resonance imaging scans can aid evaluation of carpal
      collapse, scaphoid collapse, scaphoid nonunion, bone loss, and detection of
      osteonecrosis. Nonunion of the scaphoid waist may result in a humpback deformity,
      increasing the chances of further collapse and arthrosis. This collapse deformity
      must be approached volarly with an intercalary bone graft and internal fixation.
      A dorsal approach to proximal scaphoid nonunions allows easier access for
      removing the necrotic bone from the proximal pole and applying accurate screw or
      pin fixation. Vascularized bone graft is recommended to manage scaphoid nonunions
      with osteonecrosis.

PMID- 14686824
TI  - Nonsurgical management of idiopathic clubfoot.
AB  - Because nonsurgical management was thought not to yield adequate correction and a
      durable result, most children with idiopathic clubfoot have undergone surgery
      with extensive posteromedial and lateral release. However, surgical management
      caused residual deformity, stiffness, and pain in some children; thus, the
      favorable long-term results with the Ponseti and French methods of nonsurgical
      management have garnered interest. The Ponseti method consists of manipulation
      and casting of idiopathic clubfeet; the French method consists of physiotherapy,
      taping, and continuous passive motion. Careful evaluation of the techniques and
      results of these two approaches may increase their use and decrease or minimize
      the use of surgical management and thus the associated morbidity resulting from
      extensile releases.

PMID- 14686825
TI  - Ankle fractures resulting from rotational injuries.
AB  - Ankle fractures are among the most common skeletal injuries; selection of an
      optimal management method depends on ankle stability. Stable fractures (eg,
      isolated lateral malleolar) generally are managed nonsurgically; unstable
      fractures (eg, bimalleolar, bimalleolar equivalent) usually are managed with open
      reduction and internal fixation. Stress radiographs may aid in the management of
      incomplete deltoid injury in which there is medial swelling and tenderness
      without radiographic talar shift. A posterior malleolar fracture should be
      reduced and stabilized if it comprises >30% of the articular surface and remains
      displaced after fibular stabilization. Ankle fractures with syndesmotic injury
      have additional tibiofibular instability that can be controlled by screw
      fixation. However, the choice between metal and bioabsorbable screws, screw size,
      number of cortices fixed, and indications for screw removal remain controversial.
      Conditions such as diabetes or advanced age are no longer contraindications to
      usual management recommendations.

PMID- 14686826
TI  - Childhood diskitis.
AB  - Childhood diskitis may occur in the thoracic, lumbar, or sacral spine and can
      affect children of all ages, but it is most common in the lumbar region in
      children younger than 5 years. Physical examination, laboratory tests, and
      radiologic studies all aid in the diagnosis of this clinical syndrome, and proper
      use can prevent unnecessary invasive intervention. Presentation varies with age;
      the child may refuse to bear weight on the lower extremities or may present with
      back pain, abdominal pain, a limp, or, if an infant or toddler, with
      irritability. The etiology appears to be a bacterial infection, usually caused by
      Staphylococcus aureus. Most children improve rapidly with a 4- to 6-week course
      of antibiotics. Although not routinely necessary, immobilization decreases
      symptoms and, in the case of osseous destruction, prevents progression of spinal
      deformity. Biopsy of the infected disk space is reserved for children refractory
      to intravenous antibiotics. Follow-up should include plain radiographs at regular
      intervals for 12 to 18 months to ensure resolution of the destructive process.

PMID- 14686827
TI  - Articular cartilage biology.
AB  - Articular cartilage is a complex tissue maintained by chondrocytes, which undergo
      metabolic changes as a result of aging, disease, and injury. These changes may
      hinder tissue maintenance and repair, resulting in accelerated loss of articular
      surface and leading to end-stage arthritis. Researchers are investigating both
      normal and pathologic cellular and molecular processes as well as the development
      of chondroprotective agents to improve the metabolic function of articular
      cartilage. Current research is helping to clarify the mechanisms by which a
      variety of agents, such as glucosamine, chondroitin sulfate, hyaluronic acid,
      green tea, glucocorticoids, and nonsteroidal anti-inflammatory drugs, can modify
      the symptoms and course of osteoarthritis. Also under investigation are methods
      of stimulating repair or replacing damaged cartilage, such as matrix
      metalloproteinase inhibitors, gene therapy, growth factors, cytokine inhibitors,
      and artificial cartilage substitutes. Tissue engineering, the combining of
      artificial matrices with cells and growth factors or genes, offers great
      potential for improving patient care.

PMID- 14686828
TI  - Soft-tissue injury associated with closed fractures: evaluation and management.
AB  - Determination of the severity of injury to the soft tissues is an important
      component of patient assessment and affects management of closed fractures. The
      response of soft tissue to blunt injury involves microvascular and inflammatory
      processes that produce localized tissue hypoxia and acidosis. Incisions placed
      through such compromised tissue can lead to wound breakdown and deep infection.
      Therefore, recognizing the signs of soft-tissue injury is the foundation for
      successful management of closed fractures. Many treatment options, including
      splinting, cryotherapy, compression, and delayed surgery, help limit further soft
      tissue injury and facilitate its rapid recovery before surgical intervention.
      Emerging surgical techniques based on improved management have resulted in
      decreased rates of soft-tissue complications.

PMID- 14686829
TI  - Sports and fitness activities: the negative consequences.
AB  - Participation in sports and fitness activities offers potential health benefits
      for individuals of all ages, such as combating obesity and osteoporosis, as well
      as enhancing cardiovascular fitness. Negative consequences of musculoskeletal
      injuries sustained during sports participation in childhood and adolescence may
      compromise function in later life, limiting the ability to experience pain-free
      mobility and engage in fitness-enhancing activity. Increasingly successful
      management of sports-related injuries has allowed more athletes to return to
      participation. However, even effective early management of meniscal or anterior
      cruciate ligament injury does not minimize or preclude the increased likelihood
      of developing subsequent osteoarthritis. In addition, even in the absence of
      injury, vigorous participation in sports and fitness activities during childhood
      and adolescence increases the likelihood of developing osteoarthritis. It is
      ironic that return to vigorous sports participation has been adopted as an
      important measure of success of treatment, yet few efforts have been made to
      document long-term consequences of continued participation. Awareness of the long
      term consequences of intensive sport and fitness activities allows the physician
      to help patients make informed decisions about the types and levels of activity
      they choose.

PMID- 14686830
TI  - Yttrium polyoxometalates. Synthesis and characterization of a carbonate
      encapsulated sandwich-type complex.
AB  - Reaction of A-alpha-PW(9)O(34)(9)(-) with YCl(3) in an aqueous Na(2)CO(3)
      solution produces a dianion-encapsulated A-type sandwich polyoxometalate,
      (YOH(2))(3)(CO(3))(A-alpha-PW(9)O(34))(2)(11)(-). The X-ray structure of this
      complex reveals that three Y(III) ions are sandwiched between two A-alpha
      PW(9)O(34)(9)(-) moieties and that a carbonate dianion is encapsulated in the
      same plane as the three Y(III) atoms. The oxygen atoms of the CO(3)(2)(-) are
      sitting at the midpoints of the sides of the triangle formed by the three Y(III)
      ions. (31)P and (13)C NMR studies confirm that this complex is significantly more
      stable than the analogous A-type sandwich polyoxometalates containing divalent
      metals.

PMID- 14686831
TI  - An adamantane-based coordination framework with the first observation of discrete
      metal sulfonate clusters.
AB  - By employing a rigid adamantane-based unit as a spacer, a coordination solid with
      an open channel layered structure results showing the first observation of metal
      sulfonate clusters. The design approach employed enforces a structural mismatch
      of metal and ligand coordinative preferences.

PMID- 14686832
TI  - Synthesis, characterization, and dioxygen reactivity of tetracarboxylate-bridged
      Diiron(II) complexes with coordinated substrates.
AB  - The synthesis and characterization of [Fe(2)(micro-O(2)CAr(Tol))(4)L(2)]
      complexes, where L is benzylamine or 4-methoxybenzylamine (BA(p)()(-)(OMe)), are
      described. The reaction of the latter diiron(II) complex with dioxygen at -78
      degrees C affords a metastable mixed-valent Fe(II)Fe(III) green intermediate.
      When O(2) is introduced at ambient temperature, N-dealkyation occurs to yield
      anisaldehyde, eliminating N-oxidation as a viable pathway for the reaction. Use
      of [Fe(2)(micro-O(2)CAr(T)(omicron)(l))(4)(alpha-d(1)-BA(p)()(-)(OMe))(2)]
      allowed a deuterium kinetic isotope of approximately 3 to be determined.

PMID- 14686833
TI  - An alternative route to highly luminescent platinum(II) complexes:
      cyclometalation with N=C=N-coordinating dipyridylbenzene ligands.
AB  - The remarkable luminescence properties of the platinum(II) complex of 1,3-di(2
      pyridyl)benzene, acting as a terdentate N=C=N-coordinating ligand cyclometalated
      at C2 of the benzene ring ([PtL(1)Cl]), have been investigated, together with
      those of two new 5-substituted analogues [PtL(2)Cl] and [PtL(3)Cl] [HL(2) =
      methyl-3,5-di(2-pyridyl)benzoate; HL(3) = 3,5-di(2-pyridyl)toluene]. All three
      complexes are intense emitters in degassed solution at 298 K (lambda(max) 480-580
      nm; phi(lum) = 0.60, 0.58, and 0.68 in CH(2)Cl(2)), displaying highly structured
      emission spectra in dilute solution, with lifetimes in the microsecond range
      (7.2, 8.0, and 7.8 micros). On the basis of the very small Stokes shift, the
      highly structured profiles, and the relatively long lifetimes, the emission is
      attributed to an excited state of primarily (3)pi-pi character. At concentrations
      >1 x 10(-)(5) M, structureless excimer emission centered at ca. 700 nm is
      observed. The X-ray crystal structure of [PtL(2)Cl] is also reported.

PMID- 14686834
TI  - Blue phosphors of dinuclear and mononuclear copper(I) and silver(I) complexes of
      3,5-bis(trifluoromethyl)pyrazolate and the related bis(pyrazolyl)borate.
AB  - The synthesis, structure, and photoluminescence properties are described for the
      three-coordinate mononuclear and dinuclear complexes [H(2)B(3,5
      (CF(3))(2)Pz)(2)]M(2,4,6-collidine), M(1)(), and [[3,5-(CF(3))(2)Pz]M(2,4,6
      collidine)](2), M(2)(), respectively (M = Cu; Ag). The solids exhibit bright blue
      phosphorescence, at room temperature for the copper compounds and at 77 K for all
      compounds. Ag(1)(), Cu(1)(), and Cu(2)() exhibit blue pyrazole-based structured
      emissions with short phosphorescence lifetimes, 10(1)-10(2) micros, due to an
      internal heavy-metal effect. Meanwhile, Ag(2)() exhibits curious multiple
      excitation-dependent emissions.

PMID- 14686835
TI  - cis-[Pt(NH3)2(L)]2+/+ (L = Cl, H2O, NH3) binding to purines and CO: does pi-back
      donation play a role?
AB  - The ability of cis-[Pt(NH(3))(2)(L)](2+/+), a molecular fragment of the
      anticancer drug cisplatin, to bind to purines and CO by pi-back-donation from Pt
      to the ligand was examined computationally. Optimized geometries and computed
      vibrational frequencies suggest that cis-[Pt(NH(3))(2)(L)](2+/+) (L = Cl, H(2)O,
      NH(3)) is a poor pi-donor and that pi-back-donation does not play an important
      role for Pt(II)-ligand interactions in general.

PMID- 14686836
TI  - Sequence selective hydrolysis of linear DNA using conjugates of Zr(IV) complexes
      and peptide nucleic acids.
AB  - A series of conjugates of peptide nucleic acids (PNA) and Zr(IV) complexes was
      prepared. Their ability to hydrolyze DNA was tested using MALDI-TOF mass
      spectrometry and HPLC. The most efficient artificial restriction enzyme found,
      PNA conjugate with Zr(IV) complex of tris(hydroxymethyl)-aminomethane, cleaves
      DNA targets sequence selectively in close proximity to the Zr(IV) complex. It was
      demonstrated that cleavage products are substrates of terminal transferase.

PMID- 14686837
TI  - Molybdenum chalcogenobenzimidato complexes: radical synthesis and nitrile
      extrusion via beta-EPh (E = S, Se, and Te) elimination.
AB  - Molybdenum chalcogenobenzimidates of formula (Ph[PhE]C=N)Mo(N[t-Bu]Ar)(3) (Ar =
      3,5-C(6)H(3)Me(2)) have been obtained by treatment of Mo(N[t-Bu]Ar)(3)
      sequentially with benzonitrile and 0.5 equiv of PhEEPh (E = S, Se, and Te).
      Molecular structure determinations have been carried out for the S and Se
      variants. The Te variant extrudes PhCN forming structurally characterized
      (PhTe)Mo(N[t-Bu]Ar)(3) with facility assessed via stopped-flow kinetic
      measurements, while the Se and S analogues exhibit increasing stability. Quantum
      chemical calculations and solution calorimetry have been employed as an aid to
      interpretation of the PhCN extrusion reaction.

PMID- 14686838
TI  - La3+-catalyzed methanolysis of N-aryl-beta-lactams and nitrocefin.
AB  - The kinetics of the La(3+)-catalyzed methanolysis of N-phenyl-beta-lactam (2) and
      N-p-nitrophenyl-beta-lactam (3) as well as that of nitrocefin (1) were studied at
      25 degrees C under buffered conditions. In the case of 2 and 3, the observed
      second-order rate constants (k(2)(obs)) for catalysis plateau at pH 7.5-7.8,
      reaching values of 1 x 10(-)(2) and 35 x 10(-)(2) M(-)(1) s(-)(1) respectively.
      Potentiometric titrations of solutions of 2 x 10(-)(3) M La(OTf)(3) were analyzed
      in terms of a dimer model (La(3+)(2)((-)OCH(3))(n)()), where the number of
      methoxides varies from 1 to 5. The species responsible for catalysis in the pH
      range investigated contain 1-3 methoxides, the one having the highest catalytic
      activity being La(3+)(2)((-)OCH(3))(2), which comprises 80% of the total La(3+)
      forms present at its pH maximum of 8.9. The catalysis afforded by the La(3+)
      dimers at a neutral pH is impressive relative to the methoxide reactions: at pH
      8.4 a 1 mM solution of catalyst (generated from 2 mM La(OTf)(3)) accelerated the
      methanolysis of 2 by approximately 2 x 10(7)-fold and 3 by approximately 5 x
      10(5)-fold. As a function of metal ion concentration, the La(3+)-catalyzed
      methanolysis of 1 proceeds by pathways involving first one bound metal ion and
      then a second La(3+) leading to a plateau in the k(obs) vs [La(3+)](total) plots
      at all pH values. The k(max)(obs) pseudo-first-order rate constants at the
      plateaus, representing the spontaneous methanolysis of La(3+)(2)(1(-)) forms, has
      a linear dependence on [(-)OCH(3)] (slope = 0.84 +/- 0.05 if all pH values are
      used and 1.02 +/- 0.03 if all but the two highest pH values are used). The
      speciation of bound 1 at a La(3+) concentrations corresponding to that of the
      onset of the kinetic plateau region was approximated through potentiometric
      titration of the nonreactive 3,5-dinitrobenzoic acid in the presence of 2 equiv
      of La(OTf)(3). A total speciation diagram for all bound forms of La(3+)(2)(1(
      ))((-)OCH(3))(n)(), where n = 0-5, was constructed and used to determine their
      kinetic contributions to the overall pH vs k(max)(obs) plot under kinetic
      conditions. Two kinetically equivalent mechanisms were analyzed: methoxide attack
      on La(3+)(2)(1(-))((-)OCH(3))(n)(), n = 0-2; unimolecular decomposition of the
      forms La(3+)(2)(1(-))((-)OCH(3))(n)(), n = 1-3.

PMID- 14686839
TI  - A [2]catenane constructed around a rhodium(III) center used as a template.
AB  - Rhodium(III) has been used as a templating metal center for building a
      [2]catenane. In the first stage, a Rh(phen)(2) motif has been incorporated into a
      large ring. Subsequently, a 2,2'-bipyridine derivative has been threaded through
      the ring, this process being driven by coordination of the chelate to the Rh(III)
      center. The formation of the second ring has been performed using the ring
      closing metathesis approach. Contrary to the other catenanes synthesized around
      transition metals, the second ring is formed at the rear of the coordination unit
      which it contains, by cyclizing two flexible end-functionalized fragments
      attached at the 4 and 4' positions of the 2,2'-bipyridine chelate.

PMID- 14686840
TI  - One-dimensional CuBr4(2-) ion array and CuBr3- ion chain included in the pi
      conducting framework composed of bis(methylthio)tetrathiafulvalenothioquinone-1,3
      dithiocarbonatodithiolemethide molecules.
AB  - The reaction of a new donor molecule having a planar but largely bent skeleton,
      bis(methylthio)tetrathiafulvalenothioquinone-1,3-dithiocarbonatodithiolemethide
      (1), with CuBr(2) in CH(3)CN/CS(2) afforded a black-colored crystal with a
      formula of 1(4).CuBr(4).2CuBr(3). In the crystal 1 molecules are one
      dimensionally stacked to form half-cut pipelike columns, which are arranged to
      construct two different shapes of channels included by a one-dimensional array of
      CuBr(4)(2)(-) ions and a bibromide-bridged linear chain of CuBr(3)(-) ions with a
      square-pyramidal geometry at the Cu atom, [CuBr(3)(-)](n)(), respectively. The
      room-temperature electrical conductivity on the single crystal of
      1(4).CuBr(4).2CuBr(3) was 2.0 x 10(-)(2) S cm(-)(1), and the temperature
      dependence of electrical conductivity was semiconducting with a large activation
      energy of 160 meV. The interactions between the neighboring Cu(II) d spins in the
      one-dimensional S = 1/2 spin systems due to CuBr(4)(2)(-) ions and CuBr(3)(-)
      ions in [CuBr(3)(-)](n)() were both antiferromagnetic, and the magnitudes were
      moderate (Weiss temperature, THETAV; = -18 K) in the former spin system and
      fairly large (coupling constant, J/k(B) = -120 K) in the latter spin system,
      which was in marked contrast to a moderate and ferromagnetic [CuBr(3)(-)](n)()
      chain in the cyclohexylammonium salt already known.

PMID- 14686841
TI  - Structural analysis of nine-coordinate lanthanide complexes: steric control of
      the metal-water distance across the series.
AB  - The structures of 10 isomorphous lanthanide (Ln) complexes of a chiral DOTA tetra
      amide ligand (L(1)), [LnL(1)(H(2)O)](CF(3)SO(3))(3).3H(2)O, crystallizing in
      space group P2(1), have been studied by single-crystal X-ray diffraction. The Ln
      coordination is a O(4)N(4) square antiprism, the O(4) base of which is capped by
      an aqua ligand. The sterically demanding position of the latter results in the
      lengthening of the Ln-OH(2) distance along the Pr to Lu series by 0.06 A (after
      allowing for the lanthanide contraction). In parallel, the distance between the
      bound water oxygen and the second-sphere water oxygen is reduced from 3.17 A (Pr)
      to 3.04 A (Lu), consistent with the enhanced hydrogen bond acceptor ability of
      the coordinated water oxygen across the series. A Cambridge Structural Database
      survey of [Ln(H(2)O)(9)](CF(3)SO(3))(3) salts (space group P6(3)/m) and of six
      reported isostructural complexes of DOTA [L(2)] revealed a similar trend. The
      implications of the resultant destabilization of the ground state structure for
      the water interchange process are discussed.

PMID- 14686842
TI  - Modeling the syn disposition of nitrogen donors at the active sites of
      carboxylate-bridged diiron enzymes. Enforcing dinuclearity and kinetic stability
      with a 1,2-diethynylbenzene-based ligand.
AB  - The syn coordination of histidine residues at the active sites of several
      carboxylate-rich non-heme diiron enzymes has been difficult to reproduce with
      small molecule model compounds. In this study, ligands derived from 1,8
      naphthyridine, phthalazine, and 1,2-diethynylbenzene were employed to mimic this
      geometric feature. The preassembled diiron(II) complex [Fe(2)(micro
      O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(THF)(2)] (1), where Ar(Tol)CO(2)(-) is the
      sterically hindered carboxylate 2,6-di(p-tolyl)benzoate, served as a convenient
      starting material for the preparation of iron(II) complexes, all of which were
      crystallographically characterized. Use of the ligand 2,7-dimethyl-1,8
      naphthyridine (Me(2)-napy) afforded the mononuclear complex
      [Fe(O(2)CAr(Tol))(2)(Me(2)-napy)] (2), whereas dinuclear [Fe(2)(micro-DMP)(micro
      O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(THF)] (3) resulted when 1,4-dimethylphthalazine
      (DMP) was employed. The dinuclear core of compound 3 is kinetically labile, as
      evidenced by the formation of [Fe(O(2)CAr(Tol))(2)(vpy)(2)] (4) upon addition of
      2-vinylpyridine (vpy). The diiron analogue of 4, [Fe(2)(micro
      O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(vpy)(2)] (5), was prepared directly from 1.
      When the sterically more demanding ligand 2,6-di(4-tert-butylphenyl)benzoate
      (Ar(4-tBuPh)CO(2)(-)) was used, mononuclear [Fe(O(2)CAr(4)(-)(tBuPh))(2)(THF)(2)]
      (6) and [Fe(O(2)CAr(4)(-)(tBuPh))(2)(DMP)(2)] (7) formed. The difficulty in
      stabilizing a dinuclear core with these simple (N)(2)-donor ligands was
      circumvented by preparing a family of 1,2-diethynylbenzene-based ligands, from
      which were readily assembled the complexes [Fe(2)(Et(2)BCQEB(Et))(micro
      O(2)CAr(Tol))(3)](OTf) (15) and [Cu(2)(Et(2)BCQEB(Et))(micro-I)(2)] (16), where
      Et(2)BCQEB(Et) is 1,2-bis(3-ethynyl-8-carboxylatequinoline)benzene ethyl ester.
      The Et(2)BCQEB(Et) framework provides both structural flexibility and the desired
      syn nitrogen donor geometry, thus serving as a good first-generation ligand in
      this class.

PMID- 14686843
TI  - Substituent and isomer effects on structural, spectroscopic, and electrochemical
      properties of dirhodium(III,II) complexes containing four identical unsymmetrical
      bridging ligands.
AB  - Substituent and isomer effects on the structural, spectroscopic, (UV-visible and
      ESR) and electrochemical properties of dirhodium(III,II) complexes containing
      four identical unsymmetrical bridging ligands are reported for seven related
      compounds of the type Rh(2)(L)(4)Cl where L = 2-(2-fluoroanilino)pyridinate (2
      Fap), 2-(2,6-difluoroanilino)pyridinate (2,6-F(2)ap), 2-(2,4,6
      trifluoroanilino)pyridinate (2,4,6-F(3)ap), or 2-(2,3,4,5,6
      pentafluoroanilino)pyridinate (F(5)ap) anion. Rh(2)(2-Fap)(4)Cl exists only in a
      (4,0) isomeric conformation while Rh(2)(2,6-F(2)ap)(4)Cl, Rh(2)(2,4,6
      F(3)ap)(4)Cl, and Rh(2)(F(5)ap)(4)Cl exist as both (4,0) and (3,1) isomers. It
      had earlier been demonstrated that Rh(2)(L)(4)Cl complexes can adopt different
      geometric conformations of the bridging ligands, but the current study provides
      the first example where two geometric isomers of Rh(2)(5+) complexes are obtained
      for one compound using the same synthetic procedure. The synthesis, structural,
      spectroscopic, and/or electrochemical properties of (3,1) Rh(2)(2,6-F(2)ap)(4)CN
      and (4,0) Rh(2)(2,4,6-F(3)ap)(4)(C triple bond C)(2)Si(CH(3))(3) are also
      reported and the data on these compounds is discussed in light of their parent
      complexes, (3,1) Rh(2)(2,6-F(2)ap)(4)Cl and (4,0) Rh(2)(2,4,6-F(3)ap)(4)Cl.

PMID- 14686844
TI  - 2,6-di(pyrimidin-4-yl)pyridine ligands with nitrogen-containing auxiliaries: the
      formation of functionalized molecular clefts upon metal coordination.
AB  - A series of ligands (1-4) based on a 2,6-di(pyrimidin-4-yl)pyridine scaffold have
      been synthesized, and their abilities to form complexes with Zn(II) and Cu(II)
      have been determined using UV/vis spectroscopy in buffered aqueous solution (0.01
      M N-[2-hydroxyethyl]piperazine-N'-[3-ethanesulfonic acid] (HEPES) at pH = 6.8).
      The Zn(II) complex of 1 was determined to have a formation constant of 8.4 x
      10(3) M(-)(1) while the formation constant of the Cu(II) complex was found to be
      1 x 10(6) M(-)(1). The presence of auxiliary amines in 2 increased the stability
      of the Zn(II) complex relative to that of 1 by a factor of over 40, suggesting
      possible coordination of the auxiliaries to the Zn(II) center. The guanidinium
      and 2-amino-4,5-dihydro-imidazolinium groups of 3 and 4 considerably diminished
      the stability of the Zn(II) and Cu(II) complexes relative to those of 1. X-ray
      crystal structures of 1-Zn, 3-Zn, 4, and 4-Zn were obtained and are discussed. A
      significant increase in the stability of 3-Zn, but not in the stability 1-Zn, was
      observed upon the addition of 1 equiv of sodium phosphate, implicating a
      stabilizing interaction of the guanidinium groups of 3-Zn and the phosphate
      anion.

PMID- 14686845
TI  - Structural study on highly oxidized states of a water oxidation complex
      [RuIII(bpy)2(H2O)]2(mu-O)4+ by ruthenium K-edge X-ray absorption fine structure
      spectroscopy.
AB  - The oxidation-induced structural change of a water-oxidizing diruthenium complex,
      [(bpy)(2)(H(2)O)Ru(III)(micro-O)Ru(III)(OH(2))(bpy)(2)](4+) (bpy = 2,2'
      bipyridine), was investigated by means of X-ray absorption spectroscopy. Ru K
      edge XANES (X-ray absorption near-edge structure) spectra from the acidic
      solution and solid precipitates obtained by oxidation showed that the absorption
      edge shifts toward higher energy with a preedge feature slightly more enhanced
      than those of the lower oxidation states. This indicates that the higher
      oxidation state has a lower symmetry due to shortening of the Ru-O bonds that
      originated from the water ligands. The EXAFS (extended X-ray absorption fine
      structure) spectra were similar to those of the lower oxidation states, whose
      analysis revealed the existence of short Ru-O double bonds and an almost linear
      Ru-O-Ru angle (169 +/- 2 degrees ). Ab initio EXAFS simulations for several
      possible structural models suggest that the dimeric structure is maintained
      during the water oxidation reaction.

PMID- 14686846
TI  - Coordination chemistry of a new cofacial binucleating macropolycycle derived from
      1,4,7-triazacyclononane.
AB  - We have prepared and characterized a new phenol-based compartmental ligand
      (H(2)L) incorporating 1,4,7-triazacyclononane ([9]aneN(3)), and we have
      investigated its coordination behavior with Cu(II), Zn(II), Cd(II), and Pb(II).
      The protonation constants of the ligand and the thermodynamic stabilities of the
      1:1 and 2:1 (metal/ligand) complexes with these metal ions have been investigated
      by means of potentiometric measurements in aqueous solutions. The mononuclear
      [M(L)] complexes show remarkably high stability suggesting that, along with the
      large number of nitrogen donors available for metal binding, deprotonated
      phenolic functions are also involved in binding the metal ion. The mononuclear
      complexes [M(L)] show a marked tendency to add a second metal ion to afford
      binuclear species. The formation of complexes [M(2)(H(2)L)](4+) occurs at neutral
      or slightly acidic pH and is generally followed by metal-assisted deprotonation
      of the phenolic groups to give [M(2)(HL)](3+) and [M(2)(L)](2+) in weakly basic
      solutions. The complexation properties of H(2)L have also been investigated in
      the solid state. Crystals suitable for X-ray structural analysis were obtained
      for the binuclear complexes [Cu(2)(L)](BF(4))(2).(1)/(2)MeCN (1),
      [Zn(2)(HL)](ClO(4))(3).(1)/(2)MeCN (2), and [Pb(2)(L)](ClO(4))(2).2MeCN (4). In 1
      and 2, the phenolate O-donors do not bridge the two metal centers, which are,
      therefore, segregated each within an N(5)O-donor compartment. However, in the
      case of the binuclear complex [Pb(2)(L)](ClO(4))(2).2MeCN (4), the two Pb(II)
      centers are bridged by the phenolate oxygen atoms with each metal ion sited
      within an N(5)O(2)-donor compartment of L(2)(-), with a Pb.Pb distance of
      3.9427(5) A.

PMID- 14686847
TI  - Standard absolute entropy, S degrees 298 values from volume or density. 1.
      Inorganic materials.
AB  - Standard absolute entropies of many inorganic materials are unknown; this
      precludes a full understanding of their thermodynamic stabilities. It is shown
      here that formula unit volume, V(m)(), can be employed for the general estimation
      of standard entropy, S degrees 298 values for inorganic materials of varying
      stoichiometry (including minerals), through a simple linear correlation between
      entropy and molar volume. V(m)() can be obtained from a number of possible
      sources, or alternatively density, rho, may be used as the source of data. The
      approach can also be extended to estimate entropies for hypothesized materials.
      The regression lines pass close to the origin, with the following formulas: For
      inorganic ionic salts, S degrees 298 /J K(-)(1) mol(-)(1) = 1360 (V(m)()/nm(3)
      formula unit(-)(1)) + 15 or = 2.258 [M/(rho/g cm(-)(3))] + 15. For ionic
      hydrates, S degrees 298 /J K(-)(1) mol(-)(1) = 1579 (V(m)()/nm(3) formula unit(
      )(1)) + 6 or = 2.621 [M/(rho/g cm(-)(3))] + 6. For minerals, S degrees 298 /J K(
      )(1) mol(-)(1) = 1262 (V(m)()/nm(3) formula unit(-)(1)) + 13 or = 2.095 [M/(rho/g
      cm(-)(3))] + 13. Coupled with our published procedures, which relate volume to
      other thermodynamic properties via lattice energy, the correlation reported here
      complements our development of a predictive approach to thermodynamics and
      ultimately permits the estimation of Gibbs energy data. Our procedures are
      simple, robust, and reliable and can be used by specialists and nonspecialists
      alike.

PMID- 14686848
TI  - Diastereoselectivity and molecular recognition in the self-assembly of double
      stranded dinuclear metal complexes of the type [M2[(R,S)-tetraphos]2](PF6)2 (M =
      Ag and Au).
AB  - The ligand (R,S)-Ph(2)PCH(2)CH(2)P(Ph)CH(2)CH(2)P(Ph)CH(2)CH(2)PPh(2), (R,S)
      tetraphos, combines with silver(I) and gold(I) ions in the presence of
      hexafluorophosphate to diastereoselectively self-assemble the head-to-head (H,H)
      diastereomers of the double-stranded, dinuclear metal complexes [M(2)[(R,S)
      tetraphos](2)](PF(6))(2) in which the two chiral metal centers in the complexes
      have M (R end of phosphine) and P (S end of phosphine) configurations. The
      crystal and molecular structures of the compounds have been determined: (H,H)
      (M,P) -[Ag(2)[(R,S)-tetraphos](2)](PF(6))(2), monoclinic, P2(1)/c, a =
      10.3784(2), b = 47.320(1), c = 17.3385(4) A, beta = 103.8963(5) degrees, Z = 4;
      (H,H)-(M,P)-[Au(2)[(R,S)-tetraphos](2)](PF(6))(2), monoclinic, P.2(1) (No. 4, c
      unique axis), a = 24.385(4), b = 46.175(3), c = 14.820(4) A, Z = 8. The complexes
      crystallize as racemic compounds in which the unit cell in each case contains
      equal numbers of enantiomorphic molecules of the cation and associated anions.
      The cations in both structures have similar side-by-side structures of idealized
      C(2) symmetry, the bulk helicity of each molecule in the solid state being due
      solely to the twist of the central ten-membered ring containing the two metal
      ions of opposite configuration, which has the chiral twist-boat-chair-boat
      conformation. When 1 equiv each of (R,S)-tetraphos, (R,R)-(+/-)-tetraphos, (S,S)
      (+)-tetraphos, 2 equiv of Ph(2)PCH(2)CH(2)PPh(2) (dppe), and 7 equiv of
      [AuCl(SMe(2))] in dichloromethane are allowed to react for several minutes in the
      presence of an excess of ammonium hexafluorophosphate in water (two phases), the
      products are the double-stranded digold(I) complexes in which each ligand strand
      has recognized itself by stereoselective self-assembly, together with
      [Au(dppe)(2)]PF(6).

PMID- 14686849
TI  - Crystal structures and magnetic properties of 2,3,5,6-tetrakis(2-pyridyl)pyrazine
      (tppz)-containing copper(II) complexes.
AB  - Four new copper(II) complexes of formula [Cu(2)(tppz)(dca)(3)(H(2)O)].dca.3H(2)O
      (1), [Cu(5)(tppz)(N(3))(10)](n)() (2),
      [[Cu(2)(tppz)(N(3))(2)][Cu(2)(N(3))(6)]](n)() (3), and
      [Cu(tppz)(N(3))(2)].0.33H(2)O (4) [tppz = 2,3,5,6-tetrakis(2-pyridyl)pyrazine and
      dca = dicyanamide anion] have been synthesized and structurally characterized by
      X-ray diffraction methods. The structure of complex 1 is made up of dinuclear
      tppz-bridged [Cu(2)(tppz)(dca)(3)(H(2)O)](+) cations, uncoordinated dca anions,
      and crystallization water molecules. The copper-copper separation across bis
      terdentate tppz is 6.5318(11) A. Complex 2 is a sheetlike polymer whose
      asymmetric unit contains five crystallographically independent copper(II) ions.
      These units are building blocks in double chains in which the central part
      consists of a zigzag string of copper atoms bridged by double end-on azido
      bridges, and the outer parts are formed by dinuclear tppz-bridged entities which
      are bound to the central part through single end-on azido bridges. The chains are
      furthermore connected through weak, double out-of-plane end-on azido bridges,
      yielding a sheet structure. The intrachain copper-copper separations in 2 are
      6.5610(6) A across bis-terdentate tppz, 3.7174(5) and 3.8477(5) A across single
      end-on azido bridges, and from 3.0955(5) to 3.2047(7) A across double end-on
      azido bridges. The double dca bridge linking the chains into sheets yields a
      copper-copper separation of 3.5984(7) A. The structure of 3 consists of
      centrosymmetric [Cu(2)(tppz)(N(3))(2)](2+) and [Cu(2)(N(3))(6)](2)(-) units which
      are linked through axial Cu.N(azido) (single end-on and double end-to-end
      coordination modes) type interactions to afford a neutral two-dimensional
      network. The copper-copper separations within the cation and anion are is
      6.5579(5) A (across the bis-terdentate tppz ligand) and 3.1034(6) A (across the
      double end-on azido bridges), whereas those between the units are 3.6652(4) A
      (through the single end-on azido group) and 5.3508(4) A (through the double end
      to-end azido bridges). The structure of complex 4 is built of neutral
      [Cu(tppz)(N(3))(2)] mononuclear units and uncoordinated water molecules. The
      mononuclear units are grouped by pairs to give a rather short copper-copper
      separation of 3.9031(15) A. The magnetic properties of 1-4 have been investigated
      in the temperature range 1.9-300 K. The magnetic behavior of complexes 1 and 4 is
      that of antiferromagnetically coupled copper(II) dimers with J = -43.7 (1) and 
      2.1 cm(-)(1) (4) (the Hamiltonian being H = -JS(A).S(B)). An overall
      ferromagnetic behavior is observed for complexes 2 and 3. Despite the structural
      complexity of 2, its magnetic properties correspond to those of magnetically
      isolated tppz-bridged dinuclear copper(II) units with an intermediate
      antiferromagnetic coupling (J = -37.5 cm(-)(1)) plus a ferromagnetic chain of
      hexanuclear double azido-bridged copper(II) units (the values of the magnetic
      coupling within and between the hexameric units being +61.1 and +0.0062 cm(-)(1),
      respectively). Finally, the magnetic properties of 3 were successfully analyzed
      through a model of a copper(II) chain with regular alternating of three
      ferromagnetic interactions, J(1) = +69.4 (across the double end-on azido bridges
      in the equatorial plane), J(2) = +11.2 (through the tppz bridge), and J(3) = +3.4
      cm(-)(1) (across the single end-on azido bridge).

PMID- 14686850
TI  - Thermal and photo control of the linkage isomerism of bis(thiocyanato)(2,2'
      bipyridine)platinum(II).
AB  - Three linkage isomers, bis(thiocyanato-S)(2,2'-bipyridine)platinum(II)
      ([Pt(SCN)(2)(bpy)]), (thiocyanato-S)(thiocyanato-N)(2,2'-bipyridine)platinum(II)
      ([Pt(SCN)(NCS)(bpy)]), and bis(thiocyanato-N)(2,2'-bipyridine)platinum(II)
      ([Pt(NCS)(2)(bpy)]) were isolated, and their structures were elucidated. The
      crystal data are as follows: for [Pt(SCN)(2)(bpy)], C(12)H(8)N(4)S(2)Pt,
      orthorhombic, P2(1)2(1)2(1) (No. 19), a = 12.929(9) A, b = 18.67(1) A, c =
      5.497(4) A, Z = 4; for [Pt(SCN)(NCS)(bpy)], C(12)H(8)N(4)S(2)Pt, monoclinic,
      P2(1)/n (No. 14), a = 10.909(7) A, b = 7.622(4) A, c = 16.02(1) A, beta =
      102.323(7) degrees, Z = 4; for [Pt(NCS)(2)(bpy)], C(12)H(8)N(4)S(2)Pt,
      orthorhombic, Pbcm (No. 57), a = 10.3233(8) A, b = 19.973(2) A, c = 6.4540(5) A,
      Z = 4. The stacking structures of the isomers were found to be different
      depending on the coordination geometries based on the N- and S-coordination of
      the thiocyanato ligands, which control the color and luminescence of the crystals
      sensitively. The isomerization behaviors of the complex have been investigated
      both in solution and in the solid state. In solution, stepwise thermal
      isomerization from [Pt(SCN)(2)(bpy)] to [Pt(NCS)(2)(bpy)] by way of
      [Pt(SCN)(NCS)(bpy)] was observed using (1)H NMR spectroscopy. Reverse
      isomerization, from [Pt(NCS)(2)(bpy)] to [Pt(SCN)(NCS)(bpy)] and
      [Pt(SCN)(2)(bpy)], occurred when irradiated with near ultraviolet (UV) light. In
      contrast, the [Pt(SCN)(2)(bpy)] yellow crystals exhibited thermal isomerization
      directly to red crystals of [Pt(NCS)(2)(bpy)], as detected by changes in the
      emission spectrum, which indicates that the flip of two SCN(-) ligands
      correlatively occurred in the solid state. The yellow crystals of
      [Pt(SCN)(NCS)(bpy)] were also converted to the thermodynamically stable red
      crystal of [Pt(NCS)(2)(bpy)] though the reverse isomerization has never been
      observed to occur by photoirradiation in the solid state.

PMID- 14686851
TI  - Trinuclear to dinuclear: a radii dependence lanthanide(III) self-assembly
      coordination behavior of an amide-type tripodal ligand.
AB  - Lanthanide nitrate complexes with the heptadentate ligand L (6-[2-(2
      (diethylamino)-2-oxoethoxy)ethyl]-N,N,12-triethyl-11-oxo-3,9-dioxa-6,12
      diazatetradecanamide), [Ln(2)L(NO(3))(6)] (Ln = La, Nd, Sm, Eu, Ho), have been
      prepared and characterized. The X-ray crystallographic studies show that, in
      [La(2)L(NO(3))(6)(H(2)O)].H(2)O (1), two complex cations [LaL(H(2)O)](3+) are
      linked by a hexanitrato anion [La(NO(3))(6)](3)(-) and form a trinuclear cation.
      In [Nd(2)L(NO(3))(6)(H(2)O)].CHCl(3).1/2CH(3)OH.1/2H(2)O (2), one complex cation
      [NdL(H(2)O)](3+) and a hexanitrato complex anion [Nd(NO(3))(6)](3)(-) are linked
      by a bridging NO(3)(-) to form a dinuclear complex. In both complexes, the
      bridging nitrate is an unusual tetradentate ligand. The metal ions are 12
      coordinated in hexanitrato anions and 10-coordinated in complex cations. The
      chainlike supramolecular structures of La(3+) complex are parallel and have no
      hydrogen bonds in between, while, in the Nd(3+) complex, a chiral cavity is
      formed by hydrogen bonds between two adjacent supramolecular chains. These
      influences are further investigated by assessing the separation efficiency of L
      and (1)H NMR spectra of its lanthanide nitrate mixtures in solution.

PMID- 14686852
TI  - Dirhodium formamidinate compounds with bidentate nitrogen chelating ligands.
AB  - The reactions of [Rh(2)(DTolF)(2)(CH(3)CN)(6)][BF(4)](2) (1) (DTolF = N,N'-di-p
      tolylformamidinate) with 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen)
      proceed with substitution of CH(3)CN molecules to give products with the N-N
      ligands chelating in an equatorial-equatorial (eq-eq) fashion. Compound 1 reacts
      with 1 equiv of bpy to yield a mixture of
      [Rh(2)(DTolF)(2)(bpy)(CH(3)CN)(3)][BF(4)](2).(CH(3))(2)CO (2a) and
      [Rh(2)(DTolF)(2)(bpy)(CH(3)CN)(4)][BF(4)](2) (2b). Compound 2a crystallizes in
      the monoclinic space group P2(1)/n with a = 13.5856(2) A, b = 18.0402(2) A, c =
      21.4791(3) A; alpha = 90 degrees, beta = 101.044(1) degrees, gamma = 90 degrees;
      V = 5167.27(12) A(3), Z = 4, R = 0.0531, and R(w) = 0.0948. Compound 2b
      crystallizes in the monoclinic space group P2(1)/n with a = 10.9339(2) A, b =
      24.4858(1) A, c = 19.4874(3) A; alpha = 90 degrees, beta = 94.329(1) degrees,
      gamma = 90 degrees; V = 5202.38(13) A(3), Z = 4, R = 0.0459, and R(w) = 0.1140.
      The reaction of compound 1 with 2 equiv of bpy affords
      [Rh(2)(DTolF)(2)(bpy)(2)(CH(3)CN)][BF(4)](2) (3) which crystallizes in the
      monoclinic space group P2(1)/a with a = 19.4534(4) A, b = 13.8298(3) A, c =
      19.8218(5) A; alpha = 90 degrees, beta = 109.189(1) degrees, gamma = 90 degrees;
      V = 5036.5(2) A(3), Z = 4, R = 0.0589, and R(w) = 0.0860. Compound 1 reacts with
      1 equiv of phen to form
      [Rh(2)(DTolF)(2)(phen)(CH(3)CN)(3)][BF(4)](2).2C(2)H(5)OC(2)H(5) (4) which
      crystallizes in the triclinic space group P1macro with a = 12.6346(2) A, b =
      13.5872(2) A, c = 19.0597(3) A; alpha = 71.948(1) degrees, beta = 73.631(1)
      degrees, gamma = 71.380(1) degrees; V = 2886.70(8) A(3), Z = 2, R = 0.0445, and
      R(w) = 0.1207. A notable feature of the cations in 2a, 3, and 4 is the presence
      of only one axial (ax) CH(3)CN ligand, a fact that can be attributed to the
      steric effect of the formamidinate bridging ligands. Compounds 2a, 2b, 3, and 4
      were fully characterized by X-ray crystallography and (1)H NMR spectroscopy,
      whereas [Rh(2)(DTolF)(2)(phen)(2)(CH(3)CN)(2)][BF(4)](2) (5) was characterized by
      (1)H NMR spectroscopy.

PMID- 14686853
TI  - SrSn4: a superconducting stannide with localized and delocalized bond character.
AB  - The title compound is the tin-richest phase in the system Sr-Sn and is obtained
      by stoichiometric combination of the elements. SrSn(4) peritecticly decomposes
      under formation of SrSn(3) and Sn at 340 degrees C. The structure determined from
      a single crystal shows a new structure type with a novel structure motive in tin
      chemistry. It can be described by a corrugated, distorted quadratic net of tin
      atoms as the only building unit. The nets intersect at common Sn atoms, and the
      resulting channels host the Sr atoms. The structure can alternatively be
      described as an intergrowth structure of the AlB(2)-type and W-type. The atoms
      that are connected by the two shortest Sn-Sn distances (2.900 and 3.044 A) form a
      two-dimensional net consisting of hexagons of tin atoms. The hexagons have boat
      conformation in contrast to the rather similar alpha-As structure type, where
      hexagons have a chair conformation. Further tin atoms connect the two-dimensional
      net of Sn hexagons. Temperature-dependent magnetic susceptibility measurements
      show that SrSn(4) is superconducting with T(c) = 4.8 K at 10 G. LMTO band
      structure and density of states calculations verify the metallic behavior of
      SrSn(4). An analysis of the electronic structure with the help of the electron
      localization function (ELF) shows that localized covalent bonds beside
      delocalized bonds coexist in SrSn(4).

PMID- 14686854
TI  - Chemical bonding topology of ternary transition metal-centered bismuth cluster
      halides: from molecules to metals.
AB  - The bismuth polyhedra in ternary transition metal-centered bismuth cluster
      halides may form discrete molecules or ions, infinite chains, and/or infinite
      layers. The chemical bonding in many of these diverse structures is related to
      that in deltahedral boranes exhibiting three-dimensional aromaticity by replacing
      the multicenter core bond in the boranes with two-center two-electron (2c-2e)
      bonds from the central transition metal to the nearest neighbor bismuth vertices.
      Examples of discrete molecules or ions include octahedral MBi(6)(micro
      X)(12)(z)()(-) (X = Br, I; M = Rh, Ir, z = 3; M = Ru, z = 4) with exclusively 2c
      2e bonds and pentagonal bipyramidal RhBi(7)Br(8) with a 5c-4e bond in the
      equatorial pentagonal plane indicative of Mobius aromaticity. The compound
      Ru(3)Bi(24)Br(20) contains a more complicated discrete bismuth cluster ion
      Ru(2)Bi(17)(micro-Br)(4)(5+), which can be dissected into a RuBi(5) closo
      octahedron and a RuBi(8) nido capped square antiprism bridged by a
      Ru(2)Bi(4)(micro-Br)(4) structural unit. In RuBi(4)X(2) (X = Br, I), the same
      Ru(2)Bi(4)(micro-Br)(4) structural unit bridges Bi(4) squares similar to those
      found in the known Zintl ion Bi(4)(2)(-) to give infinite chains of Ru(2)Bi(4)
      octahedra. The electron counts of the RuBi(5), RuBi(8), and Ru(2)Bi(4) polyhedra
      in these structures follow the Wade-Mingos rules. A different infinite chain
      structure is constructed from fused RhBi(7/2)Bi bicapped trigonal prisms in
      Rh(2)Bi(9)Br(3). This Rh(2)Bi(9)Br(3) structure can alternatively be derived from
      alternating Rh(2/2)Bi(4) octahedra and Rh(2/)(2)Bi(5) pentagonal bipyramids with
      electron counts obeying the Wade-Mingos rules. Related chemical bonding
      principles appear to apply to more complicated layer structures such as
      Pt(3)Bi(13)I(7) containing Kagome nets of PtBi(8/2) cubes and Ni(4)Bi(12)X(3)
      containing linked chains of NiBi(6/3)Bi capped trigonal prisms.

PMID- 14686855
TI  - A study of the phase Mg2Cu6Ga5, isotypic with Mg2Zn11. A route to an icosahedral
      quasicrystal approximant.
AB  - The new title compound was synthesized by high-temperature means and its X-ray
      structure refined in the cubic space group Pm3macro, Z = 3, a = 8.278(1) A. The
      structure exhibits a 3-D framework made from a Ga(14) and Mg network within which
      large and small cavities are occupied by centered GaCu(12) icosahedral and Cu(6)
      octahedral clusters, respectively. The clusters are well bonded within the
      network. Electronic structure calculations show that a pseudogap exists just
      above the Fermi energy, and nearly all pairwise covalent interactions remain
      bonding over a range of energy above that point. Analysis suggests that the
      compound is hypoelectronic with a four-electron deficiency per unit cell, and
      such a derivative with Sc substituting for Mg is an appropriate quasicrystal
      approximant (Im3macro). Such characteristics seem to be key factors in the
      formation of icosahedral quasicrystals.

PMID- 14686856
TI  - Synthesis and characterization of the new cluster phase K39In80. Three K-In
      compounds with remarkably specific and transferable cation dispositions.
AB  - The titled compound K(39)In(80) (Pearson symbol hP238) has been synthesized by
      fusion of the elements in stoichiometric proportions in Nb containers. The
      trigonal structure was established by single-crystal X-ray means (P3macrom1, Z =
      2, a = b =17.211(2) A, c = 28.888(6) A). The crystal structure can be described
      as a three-dimensional indium network composed of five kinds of clusters: three
      types of empty In(12) icosahedra with different exo-bonding and symmetry, A (12
      exo-bonds, 3macrom), B (12 exo-bonds, m), and C (6 exo-bonds, 3macrom); an In(16)
      icosioctahedron centered by a tetrahedral In atom (D, 3m); and a rather open
      In(15) spacer (E, 3m). This new intermediate lies between K(17)In(41) and
      K(22)In(39). Remarkably specific and transferable potassium dispositions about
      each cluster anion occur in the title compound as well as in K(17)In(41) and
      K(22)In(39). This characteristic makes it easier to understand the structural
      relationships among these three compounds, which all exhibit a common K(136)
      clathrate-II network of alkali metal atoms that are stuffed by cluster anions.
      The presence of the regular cation positions is probably decisive for the
      formation of all three structures. The title compound is metallic.

PMID- 14686857
TI  - Reaction of bare VO+ and FeO+ with ammonia: a theoretical point of view.
AB  - The potential energy surfaces corresponding to the dehydration reaction of NH(3)
      by VO(+) ((3)Sigma, (1)Delta, (5)Sigma) and FeO(+) ((6)Sigma, (4)Delta) metal
      oxide cations have been investigated within the framework of the density
      functional theory in its B3LYP formulation and by employing new optimized basis
      sets for iron and vanadium. The reaction is proposed to occur through two
      hydrogen shifts from the nitrogen to the oxygen atom giving rise to multicentered
      transition states. Possible spin crossing between surfaces at different spin
      multiplicities has been considered. The energy profiles are compared with the
      corresponding ones for the insertion of bare cations to investigate the influence
      on reactivity of the presence of the oxygen ligand. The topological analysis of
      the gradient field of the electron localization function has been used to
      characterize the nature of the bonds for all the minima and transition states
      along the paths.

PMID- 14686858
TI  - Ground and excited state electronic interactions in a bis(phenanthroline)
      copper(I) complex sandwiched between two fullerene subunits.
AB  - A new fullerene-substituted phenanthroline ligand has been obtained by reaction
      of a phenanthroline derivative bearing a 1,3-phenylenebis(methylene)-tethered bis
      malonate with C(60) in a double Bingel cyclopropanation. The relative position of
      the two cyclopropane rings in the resulting bis-methanofullerene derivatives has
      been determined on the basis of the molecular symmetry (C(s)()) deduced from the
      (1)H and (13)C NMR spectra. The corresponding Cu(I) complex F-Cu-F has been
      prepared in good yields by treatment of the ligand with Cu(CH(3)CN)(4)BF(4). In
      the resulting multicomponent system, both C(60) moieties are in a tangential
      orientation relative to their bridging phenyl ring, and the central
      bis(phenanthroline)Cu(I) core is sandwiched between the two carbon spheres. The
      electrochemical properties of F-Cu-F suggest the existence of ground-state
      electronic interactions in this multicomponent array based on the mutual effects
      exerted by the fullerene units to the bis(2,9-diphenyl-1,10-phenanthroline)Cu(I)
      complex and vice versa. Close vicinity and electronic interactions between the
      inorganic core and the peripheral fullerene units are also suggested by increased
      electronic absorption around 430 nm. The distance between the two moieties is
      estimated to be 4.3 A by molecular modeling studies. The excited-state properties
      of F-Cu-F have also been investigated. Photoinduced electron transfer from the
      central chromophore to the external fullerene units occurs but, surprisingly,
      only following population of the excited states of the central inorganic unit and
      not of the external carbon spheres. This is mainly attributed to kinetic factors
      related to the different nature of the two types of excited states involved,
      namely charge transfer (excitation on the metal-complexed moiety) vs a localized
      state (excitation on the fullerene units).

PMID- 14686859
TI  - Solid-state structure dependence of the molecular distortion and spectroscopic
      properties of the Cu(I) bis(2,9-dimethyl-1,10-phenanthroline) ion.
AB  - The relation between the geometry and spectroscopic properties of a series of
      salts of the Cu(I) bis(2,9-dimethyl-1,10-phenanthroline) ion,
      (Cu((I))(dmp)(2))(+), is explored. The distortions from the idealized D(2)(d)()
      geometry, which include flattening, rocking of the dmp ligands, and displacement
      of the Cu atoms out of the dmp planes, show considerable variation, indicating
      the importance of packing forces in the crystalline environment. The change in
      the absorption spectra upon flattening of the complex, expressed as the variation
      of the angle between the dmp planes, which varies from 88 degrees in the BF(4)
      and tosylate salts to 73 degrees in the picrate, agrees qualitatively with
      parallel DFT calculations. No correlation is found between ground state geometry
      and luminescence lifetimes, recorded both at room temperature and at 16 K. The
      low temperature lifetimes vary by a factor of 8 among the (Cu((I))(dmp)(2))(+)
      salts examined, the longest lifetime (2.4 micros at 16 K) being observed for the
      tosylate salt.

PMID- 14686860
TI  - Elucidation of a Sc(I) complex by DFT calculations and reactivity studies.
AB  - Sc(BrMgL)(2)Br (L = (R(2)NCH(2)CH(2)NCMe)(2)CH, R = H) was studied by DFT methods
      leading to the conclusion that this diamagnetic formal scandium(I) system enjoys
      stabilization of its Sc-based filled d(yz)() orbital by a delta-acceptor linear
      combination of BrMgL ring orbitals. Investigation of the reactivity of
      Sc(BrMgL)(2)Br (L = (R(2)NCH(2)CH(2)NCMe)(2)CH, R = Et) with H(2)O.B(C(6)F(5))(3)
      and (HOCH(2))(2)CMe(2), respectively, led to decomposition, with LMgBr being
      isolated in the latter case.

PMID- 14686861
TI  - 1H NMR studies of nickel(II) complexes bound to oligonucleotides: a novel
      technique for distinguishing the binding locations of metal complexes in DNA.
AB  - The selective paramagnetic relaxation of oligonucleotide proton resonances of
      d(GTCGAC)(2) and d(GTGCAC)(2) by Ni(phen)(2)(L)(2+) where L = dipyridophenazine
      (dppz), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), and phenanthrenequinone (phi)
      has been examined to obtain structural insight into the noncovalent binding of
      these metal complexes to DNA. In the oligonucleotide d(GTCGAC)(2), preferential
      broadening of the G1H8, G4H8, T2H6, and C3H6 proton resonances was observed with
      Ni(phen)(2)(dppz)(2+), Ni(phen)(2)(dpq)(2+), and Ni(phen)(2)(phi)(2+). In the
      case of the sequence d(GTGCAC)(2), where the central two bases are juxtaposed
      from the previous one, preferential broadening was observed instead for the A5H2
      proton resonance. Thus, a subtle change in the sequence of the oligonucleotide
      can cause significant change in the binding location of the metal complex in the
      oligonucleotide. Owing to comparable changes for all metal complexes and
      sequences in broadening of the thymine methyl proton resonances, we attribute the
      switch in preferential broadening to a change in site location within the
      oligomer rather than to an alteration of groove location. Therefore, even for DNA
      binding complexes of low sequence-specificity, distinct variations in binding as
      a function of sequence are apparent.

PMID- 14686862
TI  - Octahedral niobium chloride clusters as building blocks of templated prussian
      blue framework analogues.
AB  - The preparation, structure, and magnetic properties of the first three
      dimensional framework containing octahedral niobium cyanochloride clusters as
      building units are reported. Reactions of aqueous solutions of
      (Me(4)N)(2)K(2)[Nb(6)Cl(12)(CN)(6)] (2) with aqueous solutions of MnCl(2) result
      in the precipitation of the compound (Me(4)N)(2)[MnNb(6)Cl(12)(CN)(6)] (3). The
      structure of 3 was determined from single-crystal X-ray diffraction study
      (crystal data: cubic, Fm3macrom(No. 225), a = 15.513(4) A, V = 3733.2(12) A(3), Z
      = 4). Its 3D framework is based on edge-bridged [Nb(6)Cl(12)](2+) clusters and
      Mn(2+) ions bridged by cyanide ligands to form a cfc lattice
      [MnNb(6)Cl(12)(CN)(6)](2)(-) in which all tetrahedral sites are occupied by the
      cations (Me(4)N)(+) which act as charge compensating template. The structure of 3
      can be considered as an expansion of the Prussian blue framework in which
      [Fe(CN)(6)](4)(-) is replaced by the cluster [Nb(6)Cl(12)(CN)(6)](4)(-). Magnetic
      susceptibility measurements indicate that Mn(2+) is present in a high spin d(5)
      configuration. No magnetic ordering is observed.

PMID- 14686863
TI  - Mono-, di-, and tetranuclear ruthenium(II) complexes containing 3-(pyridin-2-yl)
      as-triazino[5,6-f]1,10-phenanthroline: synthesis, characterization, and
      electrochemical and photophysical properties.
AB  - Mono-, di-, and tetranuclear Ru(II) polypyridine complexes based on the bridging
      ligand pdtp, where pdtp is 3-(pyridin-2-yl)-as-triazino[5,6-f]1,10
      phenanthroline, have been synthesized and characterizated. This asymmetric
      bridging ligand is composed of two nonequivalent coordinating sites: one involves
      the phenanthroline moiety, and the other one involves the pyridyltriazine moiety.
      Electrochemical data show that the first redox process in these complexes is pdtp
      based and the metal-metal interaction in di- and tetranuclear complexes is very
      weak. The two oxidations (+1.41 and +1.56 V vs SCE) observed in dinuclear complex
      2 are mainly ascribed to the different coordination environments of two metal
      centers. Absorption spectra are essentially the sum of the spectra of the
      component monometallic species. The emission spectra are measured both at room
      temperature and at 80 K in a 4:1 (v/v) EtOH/MeOH matrix. The complexes all
      display luminescence properties which are close to that featured by the parent
      [Ru(phen)(3)](2+) species. It is also noted that center-to-periphery energy
      transfer occurs in the dendritic tetranuclear complex 3.

PMID- 14686865
TI  - Self-assemblies of new rigid angular ligands and metal centers toward the
      rational construction and modification of novel coordination polymer networks.
AB  - Self-assemblies of rigid angular ligands with 120 degrees molecular angle and
      metal centers have been investigated with the aim of achieving the rational
      construction and modification of coordination polymer structures. The reactions
      of Co(NCS)(2) with 1,3-bis(trans-4-styrylpyridyl)benzene (L(1)()), 2,6-bis(trans
      4-styrylpyridyl)pyridine (L(2)()), 1,3-bis(trans-4-styrylpyrimidyl)benzene
      (L(3)()), and 1,3-bis(trans-4-styrylquinoly)benzene (L(4)()) afford complexes
      [Co(L(1)())(2)(NCS)(2)]( infinity ) (1), [Co(L(2)())(2)(NCS)(2)]( infinity ) (2),
      Co(L(3)())(2)(NCS)(2)(CH(3)OH)(2) (3), and [Co(L(4)())(NCS)(2)]( infinity ) (4),
      respectively. The resulting complexes exhibit open framework, stairlike hydrogen
      bonded chain and single-stranded helical coil structures, which are controlled by
      the variation of the geometry around the coordination site in ligands. Moreover,
      the coordination of L(1)() and L(2)() to Mn(hfac)(2) (hfac = 1,1,1,5,5,5
      hexafluoroacetylacetonate) yields single-stranded helical coordination polymers
      of [Mn(L(1)())(hfac)(2)]( infinity ) (5) and [Mn(L(2)())(hfac)(2)]( infinity )
      (6), respectively.

PMID- 14686864
TI  - Synthesis, characterization, and X-ray crystal structure of In(DOTA-AA) (AA = p
      aminoanilide): a model for 111In-labeled DOTA-biomolecule conjugates.
AB  - This report describes the synthesis and structural characterization of the indium
      complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono(p
      aminoanilide) (DOTA-AA), a model compound for (111)In-labeled DOTA-biomolecule
      conjugates. In(DOTA-AA) was prepared by reacting DOTA-AA with 1 equiv of InCl(3)
      in 0.5 M ammonium acetate buffer (pH approximately 6). It was characterized by
      spectroscopic methods (IR, ES-MS, and (1)H NMR), elemental analysis, and X-ray
      crystallography. For comparison purposes, we also prepared the complex Y(DOTA
      AA). ES-MS and (1)H NMR data are consistent with the proposed structure. HPLC
      analysis using a reversed phase method shows that the retention time of In(DOTA
      AA) is approximately 2.0 min shorter than that of Y(DOTA-AA), demonstrating that
      In(DOTA-monoamide) is more hydrophilic than Y(DOTA-monoamide). In the solid
      state, In(DOTA-AA) has a twisted square antiprismatic coordination geometry with
      all eight donor atoms (N(4)O(4)) bonded to the In center. The average In-N and In
      O distances are almost identical to those of Y-N and Y-O bonds found in Y(DOTA-d
      Phe-NH(2)) even though the ionic radius of Y(3+) is much longer than that of
      In(3+). It seems that In(3+) does not fit the coordination cavity of DOTA-AA
      perfectly. The (1)H NMR data clearly demonstrated that In(DOTA-AA) becomes
      fluxional at room temperature, most likely due to dissociation of the acetamide
      oxygen, rotation of acetate chelating arms, and inversion of ethylenic groups of
      the macrocyclic ring. Results from this study and our previous studies (Liu, S.;
      Pietryka, J.; Ellars C. E.; Edwards D. S. Bioconjugate Chem. 2002, 13, 902-913)
      suggest that the In(3+) complex of DOTA-monoamide in the solid state might be
      different from that in solution due to dissociation of the carbonyl-oxygen donor.
      Although Y(3+) and In(3+) complexes of DOTA-monoamide are both eight-coordinate
      in the solid state, the difference in their solution structures is most likely
      responsible for their difference in lipophilicity.

PMID- 14686866
TI  - Synthesis and characterization of Ru2(DMBA)4X2 (X = CN, N3, N(CN)2, I):
      controlling structural, redox, and magnetic properties with axial ligands.
AB  - Metathesis reactions between Ru(2)(DMBA)(4)Cl(2) (DMBA = N,N'
      dimethylbenzamidinate) and MX (M = Na and K) yielded bis-adduct derivatives
      Ru(2)(DMBA)(4)X(2) (X = CN (1), N(3) (2), N(CN)(2) (3)). Metathesis reactions
      between Ru(2)(DMBA)(4)(NO(3))(2) and KI resulted in Ru(2)(DMBA)(4)I(2) (4).
      Compound 1 is diamagnetic, while compounds 2-4 are paramagnetic (S = 1). Both
      compounds 1 and 2 undergo two reversible one-electron processes, an oxidation and
      a reduction, while compound 3 features a quasireversible reduction. Single
      crystal X-ray diffraction studies revealed that the Ru-Ru bond lengths are
      2.4508(9), 2.3166(7), 2.304[1], and 2.328(1) A for compounds 1-4, respectively.
      Structural and electrochemical data clearly indicate that the axial ligands
      impart a significant influence on the electronic structures of diruthenium
      species.

PMID- 14686867
TI  - Synthesis, characterization, and crystal structure of the Pd(phen)(bdt) complex.
      A DFT and TDDFT study of its ground electronic and excited states compared to
      those of analogous complexes.
AB  - The synthesis and characterization of Pd(phen)(bdt) (1) (phen = 1,10
      phenanthroline, bdt = 1,2-benzenedithiolate) is presented. 1 crystallizes in the
      monoclinic space group P2(1)/c, alpha = 11.281(4) A, b = 20.498(8) A, c =
      8.374(3) A, beta = 90.234(8), V = 1936.5(13) A(3), Z = 4, and is isostructural
      with its previously reported related complexes. The ground and low lying excited
      electronic states in 1 and in the related complexes Pd(bpy)(bdt) (2),
      Pt(bpy)(bdt) (3), Pt(bpy)(mnt) (4), and Pt(bpy)(edt) (5) [where bpy = 2,2'
      bipyridine, edt = ethylene-1,2-dithiolate, and mnt = maleonitriledithiolate] are
      studied using density functional theory techniques. The electronic properties of
      1-5 are studied using the B3LYP functional. Optimized geometries are compared to
      experimentally observed structures. Time dependent density functional theory
      (TDDFT) is employed to investigate the excited singlet and triplet states. The
      calculated energies of the lowest singlet state and the lowest triplet state in
      all five complexes are in considerable agreement with experimental data. It is
      shown that variation of both metal and dithiolate-ligand going from 1 and 2 to 3,
      4, and 5 has a substantial impact on the spectroscopic and excited-state
      properties, indicating at the same time the mixed metal/dithiolate character of
      the HOMO orbital. All the low-lying transitions are categorized as MMLL'CT
      transitions. The emissive state of all complexes is assigned as a triplet
      dithiolate/metal to diimine charge transfer with differences in the structures of
      the emissions resulting from differences in the pi dithiolate orbital of the mnt,
      bdt, and edt as well as from differences in metal.

PMID- 14686868
TI  - Syntheses, solid-state structures, and solution studies by VT 31P NMR of
      [Zn[Se2P(OEt)2]2] infinity and [Zn2[Se2P(OiPr)2]4].
AB  - Complexes [Zn[Se(2)P(OEt)(2)](2)]( infinity ) (1) and
      [Zn(2)[Se(2)P(O(i)Pr)(2)](4)] (2) are prepared from the reaction of
      Zn(ClO(4))(2).6H(2)O and (NH(4))[Se(2)P(OR)(2)] (R = Et and (i)Pr) in a molar
      ratio of 1:2 in deoxygenated water at room temperature. Positive FAB mass spectra
      show m/z peaks at 968.8 (Zn(2)L(3)(+)) and 344.8 (ZnL(+)) for 1 and m/z at 1052.8
      (Zn(2)L(3)(+)) for 2. (1)H NMR spectra exhibit chemical shifts at delta 1.43 and
      4.23 ppm for 1 and 1.41 and 4.87 ppm for 2 due to Et and (i)Pr group of dsep
      ligands. While the solid-state structure of compound 1 is a one-dimensional
      polymer via symmetrically bridging dsep ligands, complex 2 in the crystalline
      state exists as a dimer. In both 1 and 2, zinc atoms are connected by two
      bridging dsep ligands with an additional chelating ligand at each zinc atom. The
      dsep ligands exhibit bimetallic biconnective (micro(2), eta(2)) and monometallic
      biconnective (eta(2)) coordination patterns. Thus, each zinc atom is coordinated
      by four selenium atoms from two bridging and one chelating dsep ligands and the
      geometry around zinc is distorted tetrahedral. The Zn-Se distances range between
      2.422 and 2.524 A. From variable-temperature (31)P NMR studies it has been found
      that monomer and dimer of the complex are in equilibrium in solution via exchange
      of bridging and chelating ligands. However, at temperature above 40 degrees C the
      complex exists as a monomer and shows a very sharp peak while with lowering of
      the temperature the percentage of dimer increases gradually at the expense of
      monomer. Below -90 degrees C the complex exists as a dimer and two peaks are
      observed with equal intensities which are due to bridging and chelating ligands.
      (77)Se NMR spectra of both complexes at -30 degrees C exhibit three doublets due
      to the presence of monomer and dimer in solution.

PMID- 14686869
TI  - A chiral alkyltris(pyrazolyl)borate ligand: synthesis of [(Ipc)B(pz)3Mn(CO)3] and
      [(Ipc)B(pz)3Ru(p-cymene)]PF6 (Ipc = Isopinocampheyl).
AB  - The application of the reagent (Ipc)BCl(2) (Ipc = isopinocampheyl) in the
      synthesis of a new tris(pyrazolyl)borate ligand having an Ipc substituent on
      boron is described. The sodium salt is a convenient precursor for the preparation
      of the complexes [(Ipc)tris(pyrazolyl)borato]tricarbonylmanganese and
      [[(Ipc)tris(pyrazolyl)borato](p-cymene)ruthenium](+), whose X-ray crystal
      structures are reported. While little distortion of the B(pz)(3)M unit is
      observed in these complexes, steric interaction between the Ipc group and the 3
      positions of the pyrazolyl rings is noted to lead to distortion of the angles
      around the B-C bond.

PMID- 14686870
TI  - Complexes of Schiff bases and intermediates in the copper-catalyzed oxidative
      heterocyclization by atmospheric oxygen.
AB  - After complexation with copper(II) ions, Schiff bases 1a-d may undergo an
      oxidative ring closure using atmospheric oxygen to give a number of imidazo[1,5
      a]pyridines 2, an imidazo[1,5-a]imidazole 3, and an imidazo[5,1-a]isochinoline 4.
      This ligand oxidation can be performed with catalytic amounts of copper ions in
      the reaction. A catalytic cycle for the copper-catalyzed oxidative
      heterocyclization will be presented together with isolated copper complexes of
      Schiff bases 1a,b and intermediates 5 and 8 that were found by X-ray structure
      analyses which confirm this reaction scheme.

PMID- 14686871
TI  - Anion control of the self-assembly of 2,3-diarylpyrazines with silver(I) salts.
AB  - The synthesis and characterization of three one-dimensional coordination polymers
      formed on self-assembly of 2,3-diarylpyrazines with silver(I) salts are
      presented. A linear double-stranded coordination polymer was formed on self
      assembly of 2,3-bis(3'5'-dimethylphenyl)pyrazine with silver(I)
      tetrafluoroborate. An essentially linear double-strand coordination polymer was
      formed on self-assembly of 2,3-bis(3'5'-dimethylphenyl)pyrazine with silver(I)
      trifluoromethanesulfonate. In contrast a helical silver-pyrazine coordination
      polymer with extensive intrastrand pi-stacking was formed on self-assembly of 2,3
      diphenylpyrazine with silver(I) trifluoroacetate.

PMID- 14686872
TI  - Gold(I) phosphido complexes: synthesis, structure, and reactivity.
AB  - Deprotonation of the phosphine complexes Au(PHR(2))Cl with aqueous ammonia gave
      the gold(I) phosphido complexes [Au(PR(2))](n)() (PR(2) = PMes(2) (1), PCy(2)
      (2), P(t-Bu)(2) (3), PIs(2) (4), PPhMes (5), PHMes (6); Mes = 2,4,6
      Me(3)C(6)H(2), Is = 2,4,6-(i-Pr)(3)C(6)H(2), Mes = 2,4,6-(t-Bu)(3)C(6)H(2), Cy =
      cyclo-C(6)H(11)). (31)P NMR spectroscopy showed that these complexes exist in
      solution as mixtures, presumably oligomeric rings of different sizes. X-ray
      crystallographic structure determinations on single oligomers of 1-4 revealed
      rings of varying size (n = 4, 6, 6, and 3, respectively) and conformation.
      Reactions of 1-3 and 5 with PPN[AuCl(2)] gave PPN[(AuCl)(2)(micro-PR(2))] (9-12,
      PPN = (PPh(3))(2)N(+)). Treatment of 3 with the reagents HI, I(2), ArSH, LiP(t
      Bu)(2), and [PH(2)(t-Bu)(2)]BF(4) gave respectively Au(PH(t-Bu)(2))(I) (14),
      Au(PI(t-Bu)(2))(I) (15), Au(PH(t-Bu)(2))(SAr) (16, Ar = p-t-BuC(6)H(4)),
      Li[Au(P(t-Bu)(2))(2)] (17), and [Au(PH(t-Bu)(2))(2)]BF(4) (19).

PMID- 14686873
TI  - On the origin of the optical activity in the d-d transition region of tris
      bidentate Co(III) and Rh(III) complexes.
AB  - Time-dependent density functional theory (TD-DFT) has been employed to calculate
      the rotatory strengths in the d-d transition region for various tris-bidentate
      Co(III) and Rh(III) complexes. Optimized structural parameters are also reported.
      Our results confirm a previously proposed relationship between the azimuthal
      distortion of a complex containing saturated tris(diamine) and its optical
      activity. Formally d-d transitions are forbidden and should not exhibit optical
      activity. However, it is shown here that the intensity of these bands originates
      from a coupling of even ligand combination (participating in the e(g) type LUMO)
      and an odd ligand combination (participating in the t(2)(g) HOMO). For complexes
      containing planar unsaturated ligands, the signs of the d-d bands observed from
      the single-crystal circular and linear dichroisms are in accordance with the TD
      DFT predictions. It is shown that by using hypothetical Co(NH(3))(6)(3+)
      complexes it is possible to estimate the contribution from the azimuthal
      distortion to the total rotatory strengths of the saturated tris(diamine)
      complexes. A discussion is also provided of previous theoretical studies and the
      way in which these investigations rationalized the optical activity.

PMID- 14686875
TI  - Coupling of metabolism and cardiovascular responses.

PMID- 14686874
TI  - Single-nucleotide polymorphism of the urokinase-plasminogen activator gene during
      aging and transformation of human diploid kidney cell cultures.
AB  - Single-nucleotide polymorphisms (SNPs) are differences in the nucleotide sequence
      of a specific gene from different individuals. The frequency at which SNPs occur
      varies among individuals, is gene dependent, and may be influenced by the aging
      process or by mechanisms that result in cell transformation. Urokinase
      plasminogen activator (uPA) is a serine protease that is important in embryonic
      development, aging, and the onset of pathogenic conditions. The frequency of SNP
      and the stability of the SNPs in the uPA gene have not been defined with regard
      to processes that are associated with cellular aging or transformation. In this
      study, the complete nucleotide sequence has been determined for the gene encoding
      uPA from 26 human diploid kidney cell lines. The frequency of SNP occurrence
      within the uPA gene and whether this frequency changed during cellular aging, or
      after cell transformation, were determined. The results demonstrated three donor
      dependent SNPs. One SNP was located at base pair 422, which is in the region of
      the gene responsible for encoding the high-molecular weight domain of uPA (HMW
      uPA). The other SNPs were located at base pairs 691 and 822, both of which are in
      the region of the gene responsible for encoding the low-molecular weight domain
      of uPA (LMW-uPA). Single-nucleotide polymorphisms were not detected in the
      portion of the gene responsible for encoding the uPA secretion signal. Leucine or
      proline would be encoded at amino acid 141 of HMW-uPA as the result of an SNP at
      base pair 422. The SNP detected at base pair 691 would encode for lysine or
      glutamine at amino acid 231 of LMW-uPA. The SNP detected at base pair 822 would
      not change the encoded asparagine located at position 274 of the protein. The
      SNPs identified in this study were donor dependent and were not altered during
      cellular aging, or by changes in karyology due to spontaneous transformation of
      the cell line. These results demonstrate that the integrity of the uPA gene is
      stable and not subject to alterations that accompany cell aging or
      transformation.

PMID- 14686876
TI  - Elevated secretory non-pancreatic type II phospholipase A2 serum activity is
      associated with impaired endothelial vasodilator function in patients with
      coronary artery disease.
AB  - Low-grade inflammatory activity is associated with an increased risk for
      ischaemic coronary events. sPLA(2) (secretory non-pancreatic type II
      phospholipase A(2)) serum activity is increased in chronic inflammatory diseases
      and may also contribute to atherogenesis. Since the endothelium is a major target
      for inflammatory cytokines, we hypothesized that elevated serum activity of
      sPLA(2) is associated with an impaired vasodilator function in patients with
      documented CAD (coronary artery disease). Endothelium-dependent (acetylcholine,
      10-50 microg/min) and endothelium-independent (sodium nitroprusside, 2-8
      microg/min) FBF (forearm blood flow) responses were measured by venous occlusion
      plethysmography in 50 male patients with angiographically documented CAD. sPLA(2)
      serum activity was inversely correlated with acetylcholine-induced FBF responses
      ( r =-0.36; P <0.05). In addition, there was a significant correlation between
      sPLA(2) and CRP (C-reactive protein; r =0.33, P <0.02). In contrast, FBF
      responses to sodium nitroprusside did not correlate with sPLA(2) serum activity.
      In order to identify independent predictors of an impaired endothelium-dependent
      vasodilator function in patients with CAD, a multivariate analysis was performed
      including the inflammatory serum markers as well as classical risk factors of
      CAD. This analysis demonstrated that both sPLA(2) ( P <0.05) and CRP serum levels
      ( P <0.05) were the only significant independent predictors of an impaired
      acetylcholine-induced FBF response. In conclusion, elevated sPLA(2) serum
      activity is associated with a significant impairment in systemic endothelial
      vasodilator function in patients with CAD. The identification of sPLA(2) as a
      novel independent predictor for endothelial dysfunction provides another
      important clue to link a systemic marker of inflammation with coronary
      atherosclerotic disease.

PMID- 14686877
TI  - Effect of hypervolaemic haemodilution on cerebral glutamate, glycerol, lactate
      and free radicals in heatstroke rats.
AB  - In the present study, we attempted to assess the mechanisms underlying the
      neuroprotective effect of hypervolaemic haemodilution in rat heatstroke. In
      anaesthetized rats treated with normal saline (NS) immediately after the onset of
      heatstroke induced by T (a) (ambient temperature) of 42 degrees C for 88 min,
      followed by T (a) of 24 degrees C for 12 min, the values for MAP (mean arterial
      pressure), ICP (intracranial pressure), CPP (cerebral perfusion pressure), CBF
      (cerebral blood blow), brain P O(2) (partial pressure of O(2)) and striatal
      glutamate, glycerol, lactate/pyruvate ratio, hydroxyl radicals and neuronal
      damage score were 42+/-3 mmHg, 33+/-3 mmHg, 9+/-3 mmHg, 109+/-20 BPU (blood
      perfusion units), 6+/-1 mmHg, 51+/-7 micromol/l, 24+/-3 micromol/l, 124+/-32,
      694+/-22% of baseline and 2.25+/-0.05 respectively. In animals treated with 10%
      albumin immediately after the onset of heatstroke ( T (a) of 42 degrees C for 88
      min), the values for MAP, ICP, CPP, CBF, brain P O(2) and striatal glutamate,
      glycerol, lactate/pyruvate ratio, hydroxyl radicals and neuronal damage score
      were 64+/-6 mmHg, 10+/-2 mmHg, 54+/-5 mmHg, 452+/-75 BPU, 15+/-2 mmHg, 3+/-2
      micromol/l, 4+/-2 micromol/l, 7+/-3, 119+/-7% of baseline and 0.38+/-0.05
      respectively. Apparently, the heatstroke-induced arterial hypotension,
      intracranial hypertension, cerebral hypoperfusion, cerebral ischaemia, brain
      hypoxia, increased levels of striatal glutamate, glycerol, lactate/pyruvate ratio
      and hydroxyl radicals, and increased striatal neuronal damage score values were
      all attenuated significantly by the induction of hypervolaemic haemodilution in
      rats immediately at the onset of heatstroke. These results demonstrate that the
      neuroprotective effect of hypervolaemic haemodilution is associated with a
      decrease in the elevation of glutamate, glycerol, lactate and free radicals in
      brain exposed to experimental heatstroke-induced cerebral ischaemia/hypoxia
      injury.

PMID- 14686878
TI  - N-cyclohexanecarbonylpentadecylamine: a selective inhibitor of the acid amidase
      hydrolysing N-acylethanolamines, as a tool to distinguish acid amidase from fatty
      acid amide hydrolase.
AB  - Anandamide ( N-arachidonoylethanolamine) and other bioactive N-acylethanolamines
      are degraded to their corresponding fatty acids and ethanolamine. This hydrolysis
      is mostly attributed to catalysis by FAAH (fatty acid amide hydrolase), which
      exhibits an alkaline pH optimum. In addition, we have identified another amidase
      which catalyses the same reaction exclusively at acidic pH values [Ueda, Yamanaka
      and Yamamoto (2001) J. Biol. Chem. 276, 35552-35557]. In attempts to find
      selective inhibitors of this acid amidase, we screened various derivatives of
      palmitic acid, 1-hexadecanol, and 1-pentadecylamine with N-palmitoylethanolamine
      as substrate. Here we show that N-cyclohexanecarbonylpentadecylamine inhibits the
      acid amidase from rat lung with an IC50 of 4.5 microM, without inhibiting FAAH at
      concentrations up to 100 microM. The inhibition was reversible and non
      competitive. This compound also inhibited the acid amidase in intact alveolar
      macrophages. With the aid of this inhibitor, it was revealed that rat basophilic
      leukaemia cells possess the acid amidase as well as FAAH. Thus the inhibitor may
      be a useful tool to distinguish the acid amidase from FAAH in various tissues and
      cells and to elucidate the physiological role of the enzyme.

PMID- 14686879
TI  - Augmented intrinsic activity of Factor VIIa by replacement of residues 305, 314,
      337 and 374: evidence of two unique mutational mechanisms of activity
      enhancement.
AB  - Coagulation Factor VIIa (FVIIa) lacks the ability to spontaneously complete the
      conversion to a fully active enzyme after specific cleavage of an internal
      peptide bond (Arg152-Ile153) in the zymogen. Recently, several variants of FVIIa
      with enhanced intrinsic activity have been constructed. The in vitro
      characterization of these variants has shed light on molecular determinants that
      put restrictions on FVIIa in favour of a zymogen-like conformation and warrants
      continued efforts. Here we describe a new FVIIa variant with high intrinsic
      activity containing the mutations Leu305-->Val, Ser314-->Glu, Lys337-->Ala, and
      Phe374-->Tyr. The variant, called FVIIa(VEAY), processes a tripeptidyl substrate
      very efficiently because of an unprecedented, 5.5-fold lowering of the K(m)
      value. Together with a 4-fold higher substrate turnover rate this gives the
      variant a catalytic efficiency 22 times that of wild-type FVIIa, which is
      reflected in a considerably enhanced susceptibility to inhibition by antithrombin
      and other inhibitors. For instance, the affinity of FVIIa(VEAY) for the S1 probe
      and inhibitor p -aminobenzamidine is represented by an 8-fold lower K(i) value
      compared with that of FVIIa. Activation of Factor X in solution occurs about 10
      times faster with FVIIa(VEAY) than with FVIIa, due virtually exclusively to an
      increased kcat value. The high activity of FVIIa(VEAY) is not accompanied by an
      increased burial of the N-terminus of the protease domain. A comparison of the
      kinetic parameters and molecular properties of FVIIa(VEAY) with those of the
      previously described mutant V158D/E296V/M298Q-FVIIa (FVIIa(IIa)), and the
      locations of the substitutions in the two variants, reveals what appear to be two
      profoundly different structural mechanisms dictating improvements in enzymic
      performance.

PMID- 14686882
TI  - The role of individualism and the Five-Factor Model in the prediction of
      performance in a leaderless group discussion.
AB  - Personality has seen a resurgence in the work performance literature. The Five
      Factor Model (FFM) represents a set of personality factors that has received the
      most attention in recent years. Despite its popularity, the FFM may not be
      sufficiently comprehensive to account for relevant variation across performance
      dimensions or tasks. Accordingly, the present study also considers how
      individualism may predict additional variance in performance beyond the FFM. The
      study involved 152 undergraduate students who experienced a leaderless group
      discussion (LGD) exercise. Results showed that while the FFM accounted for
      variance in students' LGD performance, individualism (independence) accounted for
      additional, unique variance. Furthermore, analyses of the group compositions
      revealed curvilinear relationships between the relative amount of extraversion,
      conscientiousness, and individualism in relation to group-level performance.

PMID- 14686883
TI  - Unmitigated communion, social constraints, and psychological distress among women
      with rheumatoid arthritis.
AB  - The personality trait of unmitigated communion, an extreme focus on relationships
      that has been associated with self-neglect, has been linked to poorer outcomes
      for both men and women, but is more common among women. This longitudinal study
      is the first to examine the influence of unmitigated communion on adaptation to a
      chronic illness that affects a much greater proportion of women to men. Women
      with rheumatoid arthritis completed measures of unmitigated communion, social
      constraints, and psychological distress at study entry and repeated the distress
      measure one year later. As expected, unmitigated communion was associated with
      psychological distress. Cross-sectional moderation analyses indicated that low
      social constraints buffered the negative effects of unmitigated communion.

PMID- 14686880
TI  - Expression of pro-inflammatory markers by human dermal fibroblasts in a three
      dimensional culture model is mediated by an autocrine interleukin-1 loop.
AB  - In vivo, fibroblasts reside in connective tissues, with which they communicate in
      a reciprocal way. Such cell--extracellular matrix interactions can be studied in
      vitro by seeding fibroblasts in collagen lattices. Depending upon the mechanical
      properties of the system, fibroblasts are activated to assume defined phenotypes.
      In the present study, we examined a transcriptional profile of primary human
      dermal fibroblasts cultured in a relaxed collagen environment and found relative
      induction (>2-fold) of 393 out of approx. 7100 transcripts when compared with the
      same system under mechanical tension. Despite down-regulated proliferation and
      matrix synthesis, cells did not become generally quiescent, since they induced
      transcription of numerous other genes including matrix metalloproteinases (MMPs)
      and growth factors/cytokines. Of particular interest was the induction of gene
      transcripts encoding pro-inflammatory mediators, e.g. cyclo-oxygenase-2 (COX-2),
      and interleukins (ILs)-1 and -6. These are apparently regulated in a hierarchical
      fashion, since the addition of IL-1 receptor antagonist prevented induction of
      COX-2, IL-1 and IL-6, but not that of MMP-1 or keratinocyte growth factor (KGF).
      Our results suggest strongly that skin fibroblasts are versatile cells, which
      adapt to their extracellular environment by displaying specific phenotypes. One
      such phenotype, induced by a mechanically relaxed collagen environment, is the
      'pro-inflammatory' fibroblast. We propose that fibroblasts that are embedded in a
      matrix environment can actively participate in the regulation of inflammatory
      processes.

PMID- 14686884
TI  - The emotional costs of parents' conditional regard: a self-determination theory
      analysis.
AB  - Parents' use of conditional regard as a socializing practice was hypothesized to
      predict their children's introjected internalization (indexed by a sense of
      internal compulsion), resentment toward parents, and ill-being. In Study 1,
      involving three generations, mothers' reports of their parents' having used
      conditional regard to promote academic achievement predicted (a) the mothers'
      poor well-being and controlling parenting attitudes, and (b) their college-aged
      daughters' viewing them as having used conditional regard, thus showing both
      negative affective consequences from and intergenerational transmission of
      conditional regard. Study 2 expanded on the first by using four domains,
      including both genders, and examining mediating processes. College students'
      perceptions of their mothers' and fathers' having used conditional regard in four
      domains (emotion control, prosocial, academic, sport) were found to relate to
      introjected internalization, behavioral enactment, fluctuations in self-esteem,
      perceived parental disapproval, and resentment of parents. Introjection mediated
      the link from conditional regard to behavioral enactment. The results suggest
      that use of conditional regard as a socializing practice can promote enactment of
      the desired behaviors but does so with significant affective costs.

PMID- 14686885
TI  - Person-Environment Fit and its implications for personality development: a
      longitudinal study.
AB  - Continuity and change in Person-Environment Fit (PE Fit) and its relation to
      personality development was studied in a 4-year longitudinal study of college
      students (N=305). PE Fit demonstrated moderate rank-order stability and small
      increases in mean-levels over time. Antecedents to PE Fit included gender (being
      male), high academic ability, low agreeableness, and low neuroticism. Outcomes
      associated with PE Fit included greater personality consistency and changes in
      personality in the direction of higher self-esteem and lower agreeableness and
      neuroticism. The implications of the findings for personality development are
      discussed.

PMID- 14686886
TI  - Borderline personality features and instability of daily negative affect and self
      esteem.
AB  - We used a daily process design and multilevel modeling to examine the role of
      borderline personality features in the day-to-day stability of college students'
      negative affect and self-esteem and their reactivity to interpersonal stressors.
      At the end of each day for two weeks, students completed a checklist of daily
      stressors and measures of state affect and self-esteem. We predicted that high
      scores on a measure of borderline features would be related to more daily
      interpersonal stressors, greater negative affective and self-esteem reactivity to
      these stressors, and less day-to-day carryover of negative mood and self-esteem.
      The first and third hypotheses were supported, but not the second. The findings
      demonstrate the utility of a daily process methodology and multilevel modeling to
      study the day-to-day functioning of individuals with borderline features.

PMID- 14686887
TI  - Introducing uninteresting tasks to children: a comparison of the effects of
      rewards and autonomy support.
AB  - Two experiments compared rewards and autonomy support as methods to promote
      children's self-regulation for an uninteresting vigilance task. Dependent
      measures were ratings of positive affect, perception of the task's value, and
      free-choice engagement. ANOVA results revealed some positive effects associated
      with autonomy support, whereas no effect for rewards was found in either study.
      The outcomes of most interest were correlations between free-choice behavior and
      self-reported measures of affect and value, reflecting the level of integration
      in self-regulation. As predicted by self-determination theory (Deci & Ryan, 1985,
      1991, 2000), rewards were associated with behaviors incongruent from affect and
      value, whereas autonomy support led to integrated self-regulation. This finding
      was first detected in Study 1 and later replicated in Study 2. Together, these
      results point to autonomy support as a beneficial alternative to the common use
      of rewards.

PMID- 14686888
TI  - Identity configurations: a new perspective on identity formation in contemporary
      society.
AB  - This paper deals with the theoretical construct of "identity configuration." It
      portrays the different possible ways in which individuals configure the
      relationship among potentially conflicting identifications in the process of
      identity formation. In order to explicate these configurations, I analyzed
      narratives of identity development retold by individuals describing personal
      identity conflicts that arise within a larger context of sociocultural conflict.
      Thirty Jewish modern orthodox young adults were interviewed regarding a
      potentially conflictual identity issue (i.e. their religious and sexual
      development). Their deliberations, as described in the interviews, were examined,
      and four different configurations were identified: a configuration based on
      choice and suppression; an assimilative and synthesizing configuration; a
      confederacy of identifications; and a configuration based on the thrill of
      dissonance. The different configurations are illustrated through exemplars, and
      the possible implications of the concept of "configuration" for identity theory
      are discussed.

PMID- 14686890
TI  - SK channels and the varieties of slow after-hyperpolarizations in neurons.
AB  - Action potentials and associated Ca2+ influx can be followed by slow after
      hyperpolarizations (sAHPs) caused by a voltage-insensitive, Ca2+-dependent K+
      current. Slow AHPs are a widespread phenomenon in mammalian (including human)
      neurons and are present in both peripheral and central nervous systems. Although,
      the molecular identity of ion channels responsible for common membrane potential
      mechanisms has been largely determined, the nature of the channels that underlie
      the sAHPs in neurons, both in the brain and in the periphery, remains unresolved.
      This short review discusses why there is no clear molecular candidate for sAHPs.

PMID- 14686891
TI  - LRRN6A/LERN1 (leucine-rich repeat neuronal protein 1), a novel gene with enriched
      expression in limbic system and neocortex.
AB  - Human chromosome 15q24-q26 is a very complex genomic region containing several
      blocks of segmental duplications to which susceptibility to anxiety disorders has
      been mapped (Gratacos et al., 2001, Cell, 106, 367-379; Pujana et al., 2001,
      Genome Res., 11, 98-111). Through an in silico gene content analysis of the 15q24
      q26 region we have identifie1d a novel gene, LRRN6A (leucine-rich repeat neuronal
      6A), and confirmed its location to the centromeric end of this complex region.
      LRRN6A encodes a transmembrane leucine-rich repeat protein, LERN1 (leucine-rich
      repeat neuronal protein 1), with similarity to proteins involved in axonal
      guidance and migration, nervous system development and regeneration processes.
      The identification of homologous genes to LRRN6A on chromosomes 9 and 19 and the
      orthologous genes in the mouse genome and other organisms suggests that LERN
      proteins constitute a novel subfamily of LRR (leucine-rich repeat)-containing
      proteins. The LRRN6A expression pattern is specific to the central nervous
      system, highly and broadly expressed during early stages of development and
      gradually restricted to forebrain structures as development proceeds. Expression
      level in adulthood is lower in general but remains stable and significantly
      enriched in the limbic system and cerebral cortex. Taken together, the
      confirmation of LRRN6A's expression profile, its predicted protein structure and
      its similarity to nervous system-expressed LRR proteins with essential roles in
      nervous system development and maintenance suggest that LRRN6A is a novel gene of
      relevance in the molecular and cellular neurobiology of vertebrates.

PMID- 14686892
TI  - A reporter allele for investigating connexin 26 gene expression in the mouse
      brain.
AB  - A variety of connexins are expressed in the diverse cell types of the central
      nervous system and are thought to regulate some of the functional properties
      exhibited by immature and mature cells. A proper understanding of the role of
      specific connexins in these processes requires an unambiguous characterization of
      their spatial and temporal pattern of expression. In order to define the cellular
      distribution of connexin 26 (Cx26) in the mouse we have generated a reporter
      allele (Cx26lacZ) by genetically manipulating the locus so that the beta
      galactosidase (lacZ) gene is expressed from the endogenous Cx26 promoter. This
      modification decreased expression from the allele and resulted in embryonic
      lethality for the Cx26lacZ/lacZ genotype in accordance with previous studies on
      Cx26 knock-out animals indicating that Cx26-containing gap junctions are
      necessary for embryonic development. Despite the lower than expected transcript
      levels, the amount of lacZ protein produced in heterozygous mice was sufficient
      to label tissues known to contain Cx26, such as liver, kidney, skin, cochlea,
      small intestine, placenta and thyroid gland. In the embryonic and mature central
      nervous system, however, lacZ was restricted to meningeal cells and could not be
      detected in either neurons or glia. The absence of Cx26 mRNA in these cells could
      also be confirmed by reverse transcription-polymerase chain reaction and in situ
      hybridization. Our experiments indicate that the Cx26lacZ mouse line can be used
      as a reporter of Cx26 gene expression and suggest that Cx26, contrary to previous
      reports, is restricted to the meninges in both embryonic and adult brain.

PMID- 14686893
TI  - Reduced expression of a novel mu-opioid receptor (MOR) subtype MOR-1B in CXBK
      mice: implications of MOR-1B in the expression of MOR-mediated responses.
AB  - A novel mu-opioid receptor (MOR) subtype, named MOR-1B, derived from
      alternatively spliced variants of MOR gene, has been isolated from the rat brain.
      Here we found for the first time that CXBK recombinant-inbred mice display a
      significant reduction in the expression of MOR-1B mRNA in the brain as compared
      to that in their progenitor C57BL/6 mice. In contrast, the expression level of
      MOR-1 mRNA in the brain of CXBK mice was similar to that found in C57BL/6 mice.
      Furthermore, relatively lower levels of MOR-1B immunoreactivity were detected in
      the periaqueductal grey matter (PAG) of CXBK mice than that observed in C57BL/6
      mice. To investigate further the possible changes in MOR function to activate G
      proteins under the condition of a reduced MOR-1B expression, the guanosine-5'-o
      (3-[35S]thio)triphosphate ([35S]GTPgammaS) binding assay was performed. We found
      that the increased level of [35S]GTPgammaS bindings to whole brain membranes
      induced by a selective MOR agonist endomorphin-1 was significantly decreased in
      CXBK mice, indicating that CXBK strain can be classified as MOR-1B-knockdown
      mice. We next investigated whether intracerebroventricular (i.c.v.) pretreatment
      with an antisence oligodeoxynucleotide against exon 5 of MOR gene (MOR-1B) could
      affect the endomorphin-1-induced supraspinal antinociception. The i.c.v.
      pretreatment with antisence oligodeoxynucleotide against MOR-1B produced a
      significant reduction in the i.c.v.-administered endomorphin-1-induced
      antinociceptive effect. The present data provide first evidence that a lack of
      MOR-1B expression may, at least in part, contribute to the reduced sensitivity to
      MOR agonists in CXBK mice, and MOR-1B may play a potential role in the MOR
      mediated supraspinal antinociception.

PMID- 14686894
TI  - Developmental up-regulation of KCC2 in the absence of GABAergic and glutamatergic
      transmission.
AB  - Postsynaptic gamma-aminobutyric acid (GABA)A-mediated responses switch from
      depolarizing to hyperpolarizing during postnatal development of the rodent
      hippocampus. This is attributable to a decrease in the concentration of
      intracellular chloride set by the expression of the neuron-specific K+-Cl- co
      transporter, KCC2. A recent in vitro study [Ganguly et al. (2001) Cell, 105, 521
      532] showed that KCC2 expression may be under the trophic control of GABAA
      receptor-mediated transmission. Here we have studied the developmental expression
      of KCC2 protein in mouse hippocampal dissociated cultures as well as organotypic
      cultures. A low somatic expression level was found in neurons prior to the
      formation of the first synapses, as detected by synaptophysin immunoreactivity.
      Thereafter, KCC2 expression was strongly up-regulated during neuronal maturation.
      The developmental up-regulation of KCC2 expression was not altered by a chronic
      application (throughout the culturing period; 2-15 days in vitro) of the action
      potential blocker TTX or the N-methyl-d-aspartate (NMDA) and non-NMDA antagonists
      APV and NBQX. Blockade of GABAA-mediated transmission with picrotoxin did not
      affect the expression levels of KCC2 protein either. These data show that neither
      neuronal spiking nor ionotropic glutamatergic and GABAergic transmission are
      required for the developmental expression of KCC2 in mouse hippocampal neurons in
      vitro.

PMID- 14686895
TI  - Internalization at glutamatergic synapses during development.
AB  - Glutamate receptors are internalized from the cell membrane via clathrin-coated
      pits. However, little is known about where this occurs - whether at or near the
      synapse or at some distance from it. In this study we used immunogold
      localization in the rat brain (mainly hippocampus) to show that clathrin-coated
      pits are found both at the edge of the synaptic active zone and at further
      postsynaptic distances, including on the sides of the spine; we also localize
      these pits specifically to glutamatergic synapses. In addition, we show that
      clathrin-coated pits can internalize both N-methyl-d-aspartate (in vivo) and
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (in vitro data only)
      receptors at extrasynaptic sites not associated directly with synapses. Also,
      caveolin might be prevalent at excitatory synapses, although it is not known
      whether it is involved in receptor internalization, receptor stabilization, or
      some other function.

PMID- 14686896
TI  - MRI and in situ hybridization reveal early disturbances in brain size and gene
      expression in the megencephalic (mceph/mceph) mouse.
AB  - The mouse model for megencephaly, mceph/mceph, carries a truncating deletion in
      the Shaker-related voltage gated potassium channel gene 1. Affected mice display
      neurological disturbances and motor dysfunctions. Symptoms begin to show at 3-4
      weeks of age. The cause of the brain enlargement is not clear. To elucidate early
      events in the development of the disease we used magnetic resonance imaging (MRI)
      to quantify, over time, the increase in size of several discrete brain regions in
      the same mice at 3, 8 and 12 weeks of age. We also analysed markers for
      neuropeptides and growth factors to explore their possible involvement at an
      early stage. The results show an enlargement of the total coronal area of the
      brain already at 3 weeks of age. Total brain volume, ventral cortex, hippocampal
      formation and cerebral cortex were enlarged at 8 weeks and onwards. Thalamus,
      brainstem, cerebellum and spinal cord did not differ from controls even at 12
      weeks. We also report distinct disturbances in the expression of brain-derived
      neurotrophic factor, insulin-like growth factor binding protein 6 and several
      neuropeptides at 2 and 3 weeks of age, that is, before an obvious behavioural
      phenotype can be observed. These results provide an objective description of the
      size changes in different brain regions of the mceph/mceph mouse, and suggest
      that certain molecules could be involved in the early processes underlying these
      changes.

PMID- 14686897
TI  - Truncation of the Shaker-like voltage-gated potassium channel, Kv1.1, causes
      megencephaly.
AB  - The megencephaly mouse, mceph/mceph, displays dramatically increased brain volume
      and hypertrophic brain cells. Despite overall enlargement, the mceph/mceph brain
      appears structurally normal, without oedema, hydrocephaly or leukodystrophy, and
      with only minor astrocytosis. Furthermore, it presents striking disturbances in
      expression of trophic and neuromodulating factors within the hippocampus and
      cortex. Using a positional cloning approach we have identified the mceph
      mutation. We show that mceph/mceph mice carry an 11-base-pair deletion in the
      gene encoding the Shaker-like voltage-gated potassium channel subtype 1, Kcna1.
      The mutation leads to a frame shift and the predicted MCEPH protein is truncated
      at amino acid 230 (out of 495), terminating with six aberrant amino acids. The
      expression of Kcna1 mRNA is increased in the mceph/mceph brain. However, the C
      terminal domains of the corresponding Kv1.1 protein are absent. The putative
      MCEPH protein retains only the N-terminal domains for channel assembly and may
      congregate nonfunctional complexes of multiple Shaker-like subunits. Indeed,
      whereas Kcna2 and Kcna3 mRNA expression is normal, the mceph/mceph hippocampus
      displays decreased amounts of Kv1.2 and Kv1.3 proteins, suggesting interactions
      at the protein level. We show that mceph/mceph mice have disturbed brain
      electrophysiology and experience recurrent behavioural seizures, in agreement
      with the abnormal electrical brain activity found in Shaker mutants. However, in
      contrast to the commonly demonstrated epilepsy-induced neurodegeneration, we find
      that the mceph mutation leads to seizures with a concomitant increase in brain
      size, without overt neural atrophy.

PMID- 14686898
TI  - Glutamatergic modulation of synaptic plasticity at a PNS vertebrate cholinergic
      synapse.
AB  - The presence and the functionality of a glutamatergic regulation was studied at
      the frog neuromuscular junction (NMJ), a singly innervated cholinergic synapse.
      Bath application of glutamate reduced transmitter release without affecting nerve
      evoked presynaptic Ca2+ entry and handling. (1S,3R)-aminocyclopentanedicarboxylic
      acid (ACPD), a metabotropic glutamate receptor (mGluR) agonist, mimicked the
      effects of glutamate while (S)-alpha-methyl-4-carboxyphenylglycine (MCPG), a
      mGluR antagonist, blocked glutamate effects. MCPG had no effect on transmitter
      release evoked at low frequency (0.2 Hz) but significantly reduced synaptic
      depression (10 Hz, 80 s). This suggests that a frequency-dependent endogenous
      glutamatergic modulation is present at the frog NMJ and is mediated through
      mGluRs. Immunohistochemical labelling revealed the presence of mGluRs at the end
      plate area, primarily on muscle fibers. Functional glutamate uptake machinery was
      also found at the NMJ as blockade of glutamate transport by the inhibitor dl
      threo-beta-benzyloxyaspartate (DL-TBOA) increased high frequency-induced
      depression, suggesting that the transporters system is used to eliminate
      glutamate from the extracellular space. Moreover, immunohistochemical labelling
      revealed that glutamate-aspartate transporters (GLASTs) are predominantly present
      on perisynaptic Schwann cells (PSCs). However, local application of glutamate on
      PSCs unreliability evoked small Ca2+ responses. Hence, these data suggest that
      functional glutamatergic interactions at a purely cholinergic synapse, shape
      synaptic efficacy and short-term plasticity in a frequency-dependent fashion.

PMID- 14686899
TI  - The pattern of ocular dominance columns in cat primary visual cortex: intra- and
      interindividual variability of column spacing and its dependence on genetic
      background.
AB  - We present a comprehensive analysis of the intrinsic variability of the
      periodicity of ocular dominance columns in cat primary visual cortex (area 17)
      and its relationship to genetic background and visual experience. We
      characterized the intra-areal and interindividual variability of column spacing
      in a large set (n = 49) of ocular dominance patterns adapting a recently
      developed technique for the two-dimensional analysis of orientation column
      patterns. Patterns were obtained from three different cat colonies (termed F, M
      and D), the cats having either normal visual experience or experimentally induced
      strabismus. Two-dimensional maps of local column spacing were calculated for
      every pattern. In individual cortices, local column spacings varied by > 50% with
      the majority of column spacings ranging between 0.6 and 1.5 mm in different
      animals. In animals from colonies F and M (n = 29), the mean column spacing
      ranged between 1.03 and 1.27 mm and exhibited no significant differences, either
      between the two breeds or between strabismic and normal animals. The mean spacing
      was moderately clustered in the left and right brain hemisphere of individual
      animals but not in littermates. In animals from colony D (n = 2), average column
      spacing ranged between 0.73 and 0.95 mm, and was thus significantly different
      from the distribution of spacings in animals from breeds F and M, suggesting an
      influence of genetic factors on the layout of ocular dominance columns. Local
      column spacing exhibited a considerable systematic intra-areal variation, with
      largest spacings along the representation of the horizontal meridian and smallest
      spacings along the peripheral representation of the vertical meridian. The total
      variability of ocular dominance column spacing comprised 24% systematic intra
      areal variation, 18% interindividual differences of mean column spacing and 58%
      nonsystematic intra-areal variability.

PMID- 14686900
TI  - Evidence for vesicular glutamate transporter synapses onto gonadotropin-releasing
      hormone and other neurons in the rat medial preoptic area.
AB  - The medial preoptic area is a key structure in the control of reproduction.
      Several data suggest that excitatory amino acids are involved in the regulation
      of this function and the major site of this action is the medial preoptic region.
      Data concerning the neuromorphology of the glutamatergic innervation of the
      medial preoptic area are fragmentary. The present investigations were focused on:
      (i) the morphology of the vesicular glutamate transporter 1 (VGluT1)- and
      vesicular glutamate transporter 2 (VGluT2)-immunoreactive nerve terminals, which
      are considered to be specific to presumed glutamatergic neuronal elements, in the
      medial preoptic area of rat; and (ii) the relationship between these glutamate
      transporter-positive endings and the gonadotropin-releasing hormone (GnRH)
      neurons in the region. Single- and double-label immunocytochemistry was used at
      the light and electron microscopic level. There was a weak to moderate density of
      VGluT1- and a moderate to intense density of VGluT2-immunoreactive elements in
      the medial preoptic area. Electron microscopy revealed that both VGluT1- and
      VGluT2-immunoreactive boutons made asymmetric type synaptic contacts with
      unlabelled neurons. VGluT2-labelled, but not VGluT1-labelled, axon terminals
      established asymmetric synaptic contacts on GnRH-immunostained neurons, mainly on
      their dendrites. The present findings are the first electron microscopic
      examinations on the glutamatergic innervation of the rat medial preoptic area.
      They provide direct neuromorphological evidence for the existence of direct
      glutamatergic innervation of GnRH and other neurons in the rat medial preoptic
      area.

PMID- 14686902
TI  - Herpes simplex virus type 1 inoculation enhances hippocampal excitability and
      seizure susceptibility in mice.
AB  - Herpes simplex virus type 1 (HSV-1) is the major pathogen related to epilepsy.
      However, little is known about the pathogenesis of HSV-1-associated epilepsy.
      Here, we report that corneal inoculation of mice with HSV-1 induces acute
      spontaneous behavioural and electrophysiological seizures and chronically
      increases hippocampal excitability and seizure susceptibility. In slices from
      infected mice, the surviving hippocampal CA3 pyramidal neurons exhibited a more
      depolarizing resting membrane potential concomitant with an increase in membrane
      input resistance. They also had a lower threshold for generating synchronized
      bursts and a decrease in the amplitude of afterhyperpolarization (AHP) than did
      controls. These results suggest that a direct change in the excitability of the
      hippocampal CA3 neuronal network could play an important role in facilitating the
      development of acute seizures and subsequent epilepsy.

PMID- 14686901
TI  - The subcellular localization of GABA(B) receptor subunits in the rat substantia
      nigra.
AB  - The inhibitory effects of GABA within the substantia nigra (SN) are mediated in
      part by metabotropic GABA(B) receptors. To better understand the mechanisms
      underlying these effects, we have examined the subcellular localization of the
      GABA(B) receptor subunits, GABA(B1) and GABA(B2), in SN neurons and afferents
      using pre-embedding immunocytochemistry combined with anterograde or retrograde
      labelling. In both the SN pars compacta (SNc) and pars reticulata (SNr), GABA(B1)
      and GABA(B2) showed overlapping, but distinct, patterns of immunolabelling.
      GABA(B1) was more strongly expressed by putative dopaminergic neurons in the SNc
      than by SNr projection neurons, whereas GABA(B2) was mainly expressed in the
      neuropil of both regions. Immunogold labelling for GABA(B1) and GABA(B2) was
      localized in presynaptic and postsynaptic elements throughout the SN. The
      majority of labelling was intracellular or was associated with extrasynaptic
      sites on the plasma membrane. In addition, labelling for both subunits was found
      on the presynaptic and postsynaptic membranes at symmetric, putative GABAergic
      synapses, including those formed by anterogradely labelled striatonigral and
      pallidonigral terminals. Labelling was also observed on the presynaptic membrane
      and at the edge of the postsynaptic density at asymmetric, putative excitatory
      synapses. Double immunolabelling, using the vesicular glutamate transporter 2,
      revealed the glutamatergic nature of many of the immunogold-labelled asymmetric
      synapses. The widespread distribution of GABA(B) subunits in the SNc and SNr
      suggests that GABA(B)-mediated effects in these regions are likely to be more
      complex than previously described, involving presynaptic autoreceptors and
      heteroreceptors, and postsynaptic receptors on different populations of SN
      neurons.

PMID- 14686903
TI  - Glutamate activates NF-kappaB through calpain in neurons.
AB  - Glutamate induces gene transcription in numerous physiological and pathological
      conditions. Among the glutamate-responsive transcription factors, NF-kappaB has
      been mainly implicated in neuronal survival and death. Recent data also suggest a
      role of NF-kappaB in neural development and memory formation. In non-neuronal
      cells, degradation of the inhibitor IkappaBalpha represents a key step in NF
      kappaB activation. However, little is known of how glutamate activates NF-kappaB
      in neurons. To investigate the signalling cascade involved we used primary murine
      cerebellar granule cells. Glutamate induced a rapid reduction of IkappaBalpha
      levels and nuclear translocation of the NF-kappaB subunit p65. The glutamate
      induced reduction of IkappaBalpha levels was blocked by the N-methyl-d-aspartate
      inhibitor MK801. Specific inhibitors of the proteasome, caspase 3, and the
      phosphoinositide 3-kinase had no effect on glutamate-induced IkappaBalpha
      degradation. However, inhibition of the glutamate-activated Ca2+-dependent
      protease calpain by calpeptin completely blocked IkappaBalpha degradation and
      reduced the nuclear translocation of p65. Calpeptin also partially blocked
      glutamate-induced cell death. Our data indicate that the Ca2+-dependent protease
      calpain is involved in the NF-kappaB activation in neurons in response to N
      methyl-d-aspartate receptor occupancy by glutamate. NF-kappaB activation by
      calpain may mediate the long-term effects of glutamate on neuron survival or
      memory formation.

PMID- 14686904
TI  - Central representation of bladder and colon revealed by dual transsynaptic
      tracing in the rat: substrates for pelvic visceral coordination.
AB  - The neurocircuitry underlying regulation of bladder and distal colon function by
      Barrington's nucleus (the pontine micturition centre) was investigated in rats by
      identifying neurons which were transsynaptically labelled from these viscera,
      with pseudorabies virus (PRV) or genetically modified forms of PRV [PRV-beta
      galactosidase (PRV-beta-Gal) and PRV-green fluorescent protein (PRV-GFP)]. PRV
      injection into the bladder or the colon of separate rats suggested an overlap in
      the distribution of bladder- and colon-related neurons in Barrington's nucleus,
      as well as a topographical arrangement whereby dorsal neurons were bladder
      related and ventral neurons were colon-related. In rats injected with PRV-beta
      Gal into one viscera and PRV-GFP into another, neurons in the major pelvic
      ganglion and lumbosacral spinal cord were primarily single-labelled at relatively
      early survival times. With longer survival times many double-labelled neurons
      (>70%) appeared in Barrington's nucleus, suggesting that individual Barrington's
      nucleus neurons are synaptically linked to preganglionic parasympathetic neurons
      which independently innervate the colon or the bladder. In addition to these dual
      labelled neurons, Barrington's nucleus neurons which were single-labelled from
      either viscera were observed and these exhibited a viscerotopic organization
      consistent with the single-labelling studies. Together, these findings suggest
      the existence of three neuronal populations in Barrington's nucleus, one which is
      synaptically linked to both the bladder and the colon and the other two
      populations which are specifically linked to either viscera. These anatomical
      substrates may underlie the central coordination of bladder and colon function
      and play a role in disorders characterized by a coexistence of bladder and
      colonic symptoms.

PMID- 14686905
TI  - Convergent responses of Barrington's nucleus neurons to pelvic visceral stimuli
      in the rat: a juxtacellular labelling study.
AB  - Barrington's nucleus impacts on bladder and distal colon function and relays
      pelvic visceral information to the forebrain. This study investigated processing
      of information from the bladder and the distal colon by Barrington's nucleus in
      the rat. The responses of individual Barrington's nucleus neurons to bladder
      and/or colon distention were characterized using extracellular recording and the
      recorded neurons were identified using juxtacellular labelling. Most neurons
      within Barrington's nucleus (79%) were activated by bladder distention,
      consistent with its role as a pontine micturition centre. Although no neurons
      were selectively responsive to colon distention, the majority of bladder
      responsive neurons (73%) were also activated by colon distention. In a second
      study, Barrington's nucleus neurons were characterized with respect to their
      response to colon distention and their immunoreactivity for the stress-related
      neuropeptide corticotropin-releasing factor (CRF). Of 30 labelled neurons in the
      central part of Barrington's nucleus, 53% were activated by colon distention and
      63% of these were CRF-ir. This is the first report demonstrating that
      Barrington's nucleus neurons are responsive to colon distention. The results
      provide evidence for convergence of information from the bladder and the colon
      onto individual Barrington's nucleus neurons. Taken with evidence that many
      Barrington's nucleus neurons are synaptically linked to the bladder and colon,
      the present study suggests a role for these neurons in coordinating peripheral
      parasympathetic and central responses to both viscera and implicate CRF as a
      neurotransmitter in this function. Dysfunctions in this circuit may underlie the
      coexistence of colon and bladder symptoms observed in functional bowel disorders.

PMID- 14686906
TI  - Glutamate receptor binding in the frontal cortex and dorsal striatum of aged rats
      with impaired attentional set-shifting.
AB  - Aged Long-Evans rats exhibit deficits in attentional set shifting, an aspect of
      executive function, relative to adult rats. Impairments in set shifting and
      spatial learning are uncorrelated in aged rats, indicating a possible
      dissociation of the effects of ageing in prefrontal versus hippocampal systems.
      Ionotropic glutamate receptor binding was assessed using an in vitro
      autoradiography method in young and aged rats. The rats had been tested on a set
      shifting task that measured attentional set shifts and reversal learning, as well
      as in a spatial learning task in the Morris water maze. [3H]Kainate, [3H]AMPA and
      NMDA-displaceable [3H]glutamate receptor binding were quantified in orbital
      cortex, cingulate cortex, medial frontal cortex, dorsolateral and dorsomedial
      striatum. Age-related decreases in [3H]kainate binding were apparent in all
      regions measured. Similarly, NMDA-displaceable [3H]glutamate binding was
      decreased in the aged rats in all the regions measured except for the medial
      frontal area where no age effects were observed. [3H]AMPA receptor binding was
      preserved with age in all the regions measured. Lower levels of [3H]kainate
      binding in the cingulate cortex were significantly correlated with poorer set
      shifting performance, whereas higher levels of NMDA binding in the dorsomedial
      striatum were correlated with poorer set-shifting performance. There were no
      significant correlations between the levels of ionotropic glutamate receptors and
      performance in the reversal task or spatial learning in the Morris water maze.
      These results indicate that age-related behavioural deficits in attentional set
      shifting are selectively associated with neurobiological alterations in the
      cingulate cortex and dorsomedial striatum.

PMID- 14686907
TI  - Ca2+-independent muscarinic excitation of rat medial entorhinal cortex layer V
      neurons.
AB  - Cholinergic activation of entorhinal cortex (EC) layer V neurons plays a crucial
      role in the medial temporal lobe memory system and in the pathophysiology of
      temporal lobe epilepsy. Here, we demonstrate that muscarinic activation by focal
      application of carbachol depolarizes EC layer V neurons and induces epileptiform
      activity in rat brain slices. These seizure-like bursts are associated with a
      somatic [Ca2+]i increase of 293 +/- 82 nm and are blocked by the glutamate
      receptor antagonists CNQX and APV. Muscarinic activation did not directly evoke a
      [Ca2+]i increase, but subthreshold and suprathreshold depolarization did.
      Functional axon mapping revealed local axon branching as well as axon collaterals
      ascending to layers II and III. During blockade of ionotropic glutamatergic AMPA
      and NMDA receptors, carbachol depolarized layer V neurons by +7.5 +/- 3.4 mV.
      This direct muscarinic depolarization was associated with a conductance increase
      of 35 +/- 10.3% (+4.3 +/- 1.25 nS). Intracellular buffering of [Ca2+]i changes
      did not block this depolarization, but prolonged action potential duration and
      reduced adaptation of action potential firing. The muscarinic depolarization was
      neither blocked by combining intracellular Ca2+-buffering (EGTA or BAPTA) with
      non-specific Ca2+-channel inhibition by Ni+ (1 mm), nor by Ba2+ (1 mm) nor during
      inhibition of the h-current by 2 mm Cs+. In whole-cell patch-clamp recording,
      reversal of the muscarinic current occurred at about -45 mV and -5 mV with
      complete substitution of intrapipette K+ with Cs+. Thus, muscarinic
      depolarization of EC layer V neurons appears to be primarily mediated by Ca2+
      independent activation of non-specific cation channels that conduct K+ about
      three times as well as Na+.

PMID- 14686908
TI  - In vivo dynamic ME-MRI reveals differential functional responses of RA- and area
      X-projecting neurons in the HVC of canaries exposed to conspecific song.
AB  - HVC (nidopallial area, formerly known as hyperstriatum ventrale pars caudalis), a
      key centre for song control in oscines, responds in a selective manner to
      conspecific songs as indicated by electrophysiology. However, immediate-early
      gene induction cannot be detected in this nucleus following song stimulation. HVC
      contains neurons projecting either towards the nucleus robustus archistriatalis
      (RA; motor pathway) or area X (anterior forebrain pathway). Both RA- and area X
      projecting cells show auditory responses. The present study analysed these
      responses separately in the two types of HVC projection neurons of canaries by a
      new in vivo approach using manganese as a calcium analogue which can be
      transported anterogradely and used as a paramagnetic contrast agent for magnetic
      resonance imaging (MRI). Manganese was stereotaxically injected into HVC and
      taken up by HVC neurons. The anterograde axonal transport of manganese from HVC
      to RA and area X was then followed by MRI during approximately 8 h and changes in
      signal intensity in these targets were fitted to sigmoid functions. Data
      comparing birds exposed or not to conspecific songs revealed that song
      stimulation specifically affected the activity of the two types of HVC projection
      neurons (increase in the sigmoid slope in RA and in its maximum signal intensity
      in area X). Dynamic manganese-enhanced MRI thus allows assessment of the
      functional state of specific neuronal populations in the song system of living
      canaries in a manner reminiscent of functional MRI (but with higher resolution)
      or of 2-deoxyglucose autoradiography (but in living subjects).

PMID- 14686909
TI  - Disruption of prepulse inhibition in mice lacking mGluR1.
AB  - Sensorimotor gating, measured by prepulse inhibition of the startle response
      (PPI), is a cross-species form of information processing that is deficient in
      patients with schizophrenia and is widely used as a model to study the
      neurobiology of this disorder. The eight known metabotropic glutamate receptors
      (mGluRs) are divided into three groups on the basis of sequence homology and
      pharmacological properties. Group I consists of mGluR5 and mGluR1, both of which
      are coupled positively to phospholipase C. Mice lacking mGluR5 exhibit a deficit
      in PPI. Like mGluR5, mGluR1 is located in regions that are involved in the
      modulation of PPI. To test the hypothesis that mGluR1 is involved in the
      modulation of PPI we assessed PPI in mGluR1 knockout (KO) mice. Littermate mGluR1
      wild-type and KO mice were tested at multiple ages in a standard PPI paradigm
      containing a 65 dB background, 120 dB pulses and prepulses of 69, 73 and 77 dB.
      At all ages tested, mGluR1 KO mice exhibited a significant PPI deficit. The PPI
      deficit of the mGluR1 KO mice was not further exaggerated by administration of
      the N-methyl-d-aspartate antagonist phencyclidine nor was it reversed by
      administration of the dopamine antagonist raclopride (3.0 mg/kg). The PPI deficit
      of the mGluR1 KO mice was, however, ameliorated by administration of the mood
      stabilizer lamotrigine (27 mg/kg base equivalent weight), though increases in PPI
      were also seen with lamotrigine in the wild-type mice. Thus, both group I
      metabotropic glutamate receptors are involved in the regulation of PPI in mice.

PMID- 14686910
TI  - Environmental enrichment during adolescence reverses the effects of prenatal
      stress on play behaviour and HPA axis reactivity in rats.
AB  - Prenatal stress (PS) can produce profound and long-lasting perturbations of
      individual adaptive capacities, which in turn can result in an increased
      proneness to behavioural disorders. Indeed, in PS rats there is evidence of
      impaired social play behaviour, disturbances in a variety of circadian rhythms,
      enhanced anxiety and increased hypothalamic-pituitary-adrenal (HPA) axis
      reactivity. This study was designed to experimentally investigate the degree of
      reversibility of PS-induced disturbances of social play and HPA reactivity by
      assessing the effect of the enrichment of the physical environment on PS rats
      during periadolescence. PS subjects showed a reduced expression of social play
      behaviour and a prolonged corticosterone secretion in response to restraint
      stress, but both these effects were markedly reversed following environmental
      enrichment. Interestingly, the enrichment procedure increased social behaviour
      but had no effect on corticosterone secretion in nonstressed animals, indicating
      a differential impact of the postnatal environment as a function of prenatal
      background. As a whole, results clearly indicate that rats prenatally exposed to
      stress can benefit during periadolescence from the modulatory effects of an
      enriched environment. Moreover, they confirm that PS may well represent a
      suitable animal model for the design and testing of new therapeutic strategies
      for behavioural disorders produced by early insults.

PMID- 14686911
TI  - Effector-independent representations of simple and complex imagined finger
      movements: a combined fMRI and TMS study.
AB  - Kinesthetic motor imagery and actual execution of movements share a common neural
      circuitry. Functional magnetic resonance imaging was used in 12 right-handed
      volunteers to study brain activity during motor imagery and execution of simple
      and complex unimanual finger movements of the dominant and the nondominant hand.
      In the simple task, a flexible object was rhythmically compressed between thumb,
      index and middle finger. The complex task was a sequential finger-to-thumb
      opposition movement. Premotor, posterior parietal and cerebellar regions were
      significantly more active during motor imagery of complex movements than during
      mental rehearsal of the simple task. In 10 of the subjects, we also used
      transcranial magnetic brain stimulation to examine corticospinal excitability
      during the same motor imagery tasks. Motor-evoked potentials increased
      significantly over values obtained in a reference condition (visual imagery)
      during imagery of the complex, but not of the simple movement. Imagery of finger
      movements of either hand activated left dorsal and ventral premotor areas and the
      supplementary motor cortex regardless of task complexity. The effector
      independent activation of left premotor areas was particularly evident in the
      simple motor imagery task and suggests a left hemispherical dominance for
      kinesthetic movement representations in right-handed subjects.

PMID- 14686912
TI  - Tangential migration of cells from the basal to the dorsal telencephalic regions
      in the chick.
AB  - The evolutionary relationship between telencephalic regions of the avian and
      mammalian brains has been a long-standing issue in comparative neuroanatomy.
      Based on various criteria, a number of homologous regions have been proposed.
      Recent studies in mammals have shown that basal regions of the telencephalon give
      rise to neurons that migrate dorsally and populate the cerebral cortex. In the
      present study we demonstrate that, similar to mammals, neurons from a ventricular
      region of the palaeo-striatal complex - the dorsal subpallial sulcus - of the
      chick telencephalon migrate dorsally to populate the developing pallium. Further
      characterization of these cells revealed that they express the neurotransmitter
      gamma-aminobutyric acid, but not the calcium-binding protein calbindin. These
      findings provide evidence that the mouse and chick basal regions are not only
      homologous in terms of gene expression patterns and connectivity, but they both
      also contribute inhibitory interneurons to dorsal regions of the developing
      telencephalon.

PMID- 14686913
TI  - Can a therapeutic dose of amphetamine during pre-adolescence modify the pattern
      of synaptic organization in the brain?
AB  - Stimulant drugs such as amphetamine have, for many decades, been the drugs of
      choice in the treatment of children with attention-deficit/hyperactivity
      disorder. However, little is known about their therapeutic mechanisms or about
      the consequences of their long-term exposure. In the present study we
      investigated whether repeated exposure of a low dose of amphetamine (0.5 mg/kg)
      to juvenile rats could induce long-term morphological alterations in the
      prefrontal cortex. In addition, to assess possible behavioural consequences of
      prolonged exposure to this drug, we examined whether changes in the motor
      response to various dopamine agonists occurred after this treatment. We found
      that this dose of amphetamine promotes plasma concentrations of amphetamine
      sulphate in juvenile rats to levels corresponding to the clinical range used for
      children with attention-deficit/hyperactivity disorder. Amphetamine (0.5 mg/kg;
      s.c.) was administered twice daily during postnatal days 22-34, and then the
      brains of the animals were evaluated 2 weeks later. This treatment produced an
      increase in dendritic length and branches of pyramidal neurons of the medial
      prefrontal cortex, but not in the nucleus accumbens. These changes were
      associated with an increase in the expression of calcium/calmodulin-dependent
      protein kinase II, a highly abundant signalling protein in the postsynaptic
      densities of excitatory synapses. Interestingly, amphetamine pre-treatment did
      not alter the motor response to various dopamine agonists, including amphetamine.
      These data suggest that clinical doses of stimulant drugs may be acting as a
      trophic support at the glutamatergic synapses, thereby enhancing dopamine
      glutamate interactions in the prefrontal cortex.

PMID- 14686914
TI  - Glutamate signaling in peripheral tissues.
AB  - The hypothesis that l-glutamate (Glu) is an excitatory amino acid
      neurotransmitter in the mammalian central nervous system is now gaining more
      support after the successful cloning of a number of genes coding for the
      signaling machinery required for this neurocrine at synapses in the brain. These
      include Glu receptors (signal detection), Glu transporters (signal termination)
      and vesicular Glu transporters (signal output through exocytotic release).
      Relatively little attention has been paid to the functional expression of these
      molecules required for Glu signaling in peripheral neuronal and non-neuronal
      tissues; however, recent molecular biological analyses show a novel function for
      Glu as an extracellular signal mediator in the autocrine and/or paracrine system.
      Emerging evidence suggests that Glu could play a dual role in mechanisms
      underlying the maintenance of cellular homeostasis - as an excitatory
      neurotransmitter in the central neurocrine system and an extracellular signal
      mediator in peripheral autocrine and/or paracrine tissues. In this review, the
      possible Glu signaling methods are outlined in specific peripheral tissues
      including bone, testis, pancreas, and the adrenal, pituitary and pineal glands.

PMID- 14686915
TI  - Active site residues and mechanism of UDP-glucose dehydrogenase.
AB  - UDP-glucose dehydrogenase catalyzes the NAD+-dependent twofold oxidation of UDP
      glucose to give UDP-glucuronic acid. A sequestered aldehyde intermediate is
      produced in the first oxidation step and a covalently bound thioester is produced
      in the second oxidation step. This work demonstrates that the Streptococcus
      pyogenes enzyme incorporates a single solvent-derived oxygen atom during
      catalysis and probably does not generate an imine intermediate. The reaction of
      UDP-[6",6"-di-2H]-d-glucose is not accompanied by a primary kinetic isotope
      effect, indicating that hydride transfer is not rate determining in this
      reaction. Studies with a mutant of the key active site nucleophile, Cys260Ala,
      show that it is capable of both reducing the aldehyde intermediate, and oxidizing
      the hydrated form of the aldehyde intermediate but is incapable of oxidizing UDP
      glucose to UDP-glucuronic acid. In the latter case, a ternary Cys260Ala/aldehyde
      intermediate/NADH complex is presumably formed, but it does not proceed to
      product as both release and hydration of the bound aldehyde occur slowly. A
      washout experiment demonstrates that the NADH in this ternary complex is not
      exchangeable with external NADH, indicating that dissociation only occurs after
      the addition of a nucleophile to the aldehyde carbonyl. Studies on Thr118Ala show
      that the value of kcat is reduced 160-fold by this mutation, and that the
      reaction of UDP-D-[6",6"-di-2H]-glucose is now accompanied by a primary kinetic
      isotope effect. This indicates that the barriers for the hydride transfer steps
      have been selectively increased and supports a mechanism in which an ordered
      water molecule (H-bonded to Thr118) serves as the catalytic base in these steps.

PMID- 14686916
TI  - Overexpression and enzymatic characterization of Neisseria gonorrhoeae penicillin
      binding protein 4.
AB  - The penicillin-binding proteins (PBPs) are ubiquitous bacterial enzymes involved
      in cell wall biosynthesis, and are the targets of the beta-lactam antibiotics.
      The low molecular mass Neisseria gonorrhoeae PBP 4 (NG PBP 4) is the fourth PBP
      revealed in the gonococcal genome. NG PBP 4 was cloned, overexpressed, purified,
      and characterized for beta-lactam binding, DD-carboxypeptidase activity, acyl
      donor substrate specificity, transpeptidase activity, inhibition by a number of
      active site directed reagents, and pH profile. NG PBP 4 was efficiently acylated
      by penicillin (30,000 m-1.s-1). Against a set of five alpha- and epsilon
      substituted l-Lys-D-Ala-D-Ala substrates, NG PBP 4 exhibited wide variation in
      specificity with a preference for N epsilon-acylated substrates, suggesting a
      possible preference for crosslinked pentapeptide substrates in the cell wall.
      Substrates with an N epsilon-Cbz group demonstrated pronounced substrate
      inhibition. NG PBP 4 showed 30-fold higher activity against the depsipeptide Lac
      ester substrate than against the analogous peptide substrate, an indication that
      k2 (acylation) is rate determining for carboxypeptidase activity. No
      transpeptidase activity was apparent in a model transpeptidase reaction. Among a
      number of active site-directed agents, N-chlorosuccinimide, elastinal,
      iodoacetamide, iodoacetic acid, and phenylglyoxal gave substantial inhibition,
      and methyl boronic acid gave modest inhibition. The pH profile for activity
      against Ac2-l-Lys-D-Ala-d-Ala (kcat/Km) was bell-shaped, with pKa values at 6.9
      and 10.1. Comparison of the enzymatic properties of NG PBP 4 with other DD
      carboxypeptidases highlights both similarities and differences within these
      enzymes, and suggests the possibility of common mechanistic roles for the two
      highly conserved active site lysines in Class A and C low molecular mass PBPs.

PMID- 14686917
TI  - The C-terminal t peptide of acetylcholinesterase forms an alpha helix that
      supports homomeric and heteromeric interactions.
AB  - Acetylcholinesterase subunits of type T (AChET) possess an alternatively spliced
      C-terminal peptide (t peptide) which endows them with amphiphilic properties, the
      capacity to form various homo-oligomers and to associate, as a tetramer, with
      anchoring proteins containing a proline rich attachment domain (PRAD). The t
      peptide contains seven conserved aromatic residues. By spectroscopic analyses of
      the synthetic peptides covering part or all of the t peptide of Torpedo AChET, we
      show that the region containing the aromatic residues adopts an alpha helical
      structure, which is favored in the presence of lipids and detergent micelles:
      these residues therefore form a hydrophobic cluster in a sector of the helix. We
      also analyzed the formation of disulfide bonds between two different AChET
      subunits, and between AChET subunits and a PRAD-containing protein [the N
      terminal fragment of the ColQ protein (QN)] possessing two cysteines upstream or
      downstream of the PRAD. This shows that, in the complex formed by four T subunits
      with QN (T4-QN), the t peptides are not folded on themselves as hairpins but
      instead are all oriented in the same direction, antiparallel to that of the PRAD.
      The formation of disulfide bonds between various pairs of cysteines, introduced
      by mutagenesis at various positions in the t peptides, indicates that this
      complex possesses a surprising flexibility.

PMID- 14686918
TI  - Modulation of activity of NADH oxidase from Thermus thermophilus through change
      in flexibility in the enzyme active site induced by Hofmeister series anions.
AB  - The conformational dynamics of NADH oxidase from Thermus thermophilus was
      modulated by the Hofmeister series of anions (H2PO4-, SO42-, CH3COO-, Cl-, Br-, I
      , ClO4-, SCN-) in the concentration range 0-3 M. Both chaotropic and kosmotropic
      anions, at high concentration, inhibit the enzyme by different mechanisms.
      Chaotropic anions increase the apparent Michaelis constant and decrease the
      activation barrier of the reaction. Kosmotropic anions have the opposite effect.
      Anions from the middle of the Hofmeister series do not significantly affect the
      enzyme activity even at high concentration. We detected no significant changes in
      ellipticity of the aromatic region in the presence of the anions studied. There
      is a decreased Stern-Volmer quenching constant for FAD fluorescence quenching in
      the presence of kosmotropic anions and an increased quenching constant in the
      presence of chaotropic anions. All of this indicates that active site flexibility
      is important in the function of the enzyme. The data demonstrate that both the
      high rigidity of the active site in the presence of kosmotropic anions, and its
      high flexibility in the presence of chaotropic anions have a decelerating effect
      on enzyme activity. The Hofmeister series of anions proved to be suitable agents
      for altering enzyme activity through changes in flexibility of the polypeptide
      chain, with potential importance in modulating extremozyme activity at room
      temperature.

PMID- 14686919
TI  - UDP-galactose 4-epimerase from Kluyveromyces fragilis. Evidence for independent
      mutarotation site.
AB  - UDP-galactose 4-epimerases from the yeast Kluyvero-myces fragilis and Escherichia
      coli are both homodimers but the molecular mass of the former (75 kDa/subunit) is
      nearly double that of the latter (39 kDa/subunit). Protein databank sequence
      homology revealed the possibility of mutarotase activity in the excess mass of
      the yeast enzyme. This was confirmed by three independent assay protocols. With
      the help of specific inhibitors and chemical modification reagents, the catalytic
      sites of epimerase and mutarotase were shown to be distinct and independent.
      Partial proteolysis with trypsin in the presence of specific inhibitors, 5'-UMP
      for epimerase and galactose for mutarotase, protected the respective activities.
      Similar digestion with double inhibitors cleaved the molecule into two fragments
      of 45 and 30 kDa. After separation by size-exclusion HPLC, they manifested
      exclusively epimerase and mutarotase activities, respectively. Epimerases from
      Kluyveromyces lactis var lactis, Pachysolen tannophilus and Schizosaccharomyces
      pombi also showed associated mutarotase activity distinct from the constitutively
      formed mutarotase activity. Thus, the bifunctionality of homodimeric yeast
      epimerases of 65-75 kDa/subunit appears to be universal. In addition to the
      inducible bifunctional epimerase/mutarotase, K. fragilis contained a smaller
      constitutive monomeric mutarotase of approximately 35 kDa.

PMID- 14686920
TI  - Stimulation-dependent recruitment of cytosolic phospholipase A2-alpha to
      EA.hy.926 endothelial cell membranes leads to calcium-independent association.
AB  - Cytosolic phospholipase A2-alpha (cPLA2-alpha) is a calcium-activated enzyme
      involved in agonist-induced arachidonic acid release. In endothelial cells, free
      arachidonic acid is predominantly converted into prostacyclin, a potent
      vasodilator and inhibitor of platelet activation. As the rate-limiting step in
      prostacyclin production is the generation of free arachidonic acid by cPLA2
      alpha, this enzyme has become an attractive pharmacological target and the focus
      of many studies. Following stimulation with calcium-mobilizing agonists, cPLA2
      alpha translocates to intracellular phospholipid membranes via its C2 domain. In
      this study, the calcium-induced association of cPLA2-alpha with EA.hy.926
      endothelial cell membranes was investigated. Subcellular fractionation and
      immunofluorescence studies showed that following stimulation with histamine,
      thrombin or the calcium ionophore A23187, cPLA2-alpha relocated to intracellular
      membranes. Treatment of A23187-stimulated cells with EGTA or BAPTA-AM
      demonstrated that a substantial pool of cPLA2-alpha remained associated with
      membrane fractions in a calcium-independent manner. Furthermore,
      immunofluorescence microscopy studies revealed that cells stimulated for periods
      of greater than 10 min showed a high proportion of calcium-independent membrane
      associated cPLA2-alpha. Calcium-independent membrane association of cPLA2-alpha
      was not due to hydrophobic or cytoskeletal interactions. Finally, the recombinant
      C2 domain of cPLA2-alpha exhibited calcium-independent membrane binding to
      membranes isolated from A23187-stimulated cells but not those isolated from
      nonstimulated cells. These findings suggest that novel mechanisms involving
      accessory proteins at the target membrane play a role in the regulation of cPLA2
      alpha. Such regulatory associations could enable the cell to discriminate between
      the varying levels of cytosolic calcium induced by different stimuli.

PMID- 14686921
TI  - Cloning and expression of murine enzymes involved in the salvage pathway of GDP-L
      fucose.
AB  - In the salvage pathway of GDP-L-fucose, free cytosolic fucose is phosphorylated
      by L-fucokinase to form L-fucose-L-phosphate, which is then further converted to
      GDP-L-fucose in the reaction catalyzed by GDP-L-fucose pyrophosphorylase. We
      report here the cloning and expression of murine L-fucokinase and GDP-L-fucose
      pyrophosphorylase. Murine L-fucokinase is expressed as two transcripts of 3057
      and 3270 base pairs, encoding proteins of 1019 and 1090 amino acids with
      predicted molecular masses of 111 kDa and 120 kDa respectively. Only the longer
      splice variant of L-fucokinase was enzymatically active when expressed in COS-7
      cells. Murine GDP-L-fucose pyrophosphorylase has an open reading frame of 1773
      base pairs encoding a protein of 591 amino acids with a predicted molecular mass
      of 65.5 kDa. GDP-L-fucose, the reaction product of GDP-L-pyrophosphorylase, was
      identified by HPLC and MALDI-TOF MS analysis. The tissue distribution of murine L
      fucokinase and GDP-L-fucose pyrophosphorylase was investigated by quantitative
      real time PCR, which revealed high expression of L-fucokinase and GDP-L-fucose
      pyrophosphorylase in various tissues. The wide expression of both enzymes can
      also be observed from the large amount of data collected from a number of
      expressed sequence tag libraries, which indicate that not only the de novo
      pathway alone, but also the salvage pathway, could have a significant role in the
      synthesis of GDP-L-fucose in the cytosol.

PMID- 14686922
TI  - Expression of mitochondrial HMGCoA synthase and glutaminase in the colonic mucosa
      is modulated by bacterial species.
AB  - The expression of the colonic mitochondrial 3-hydroxy 3-methyl glutaryl CoA
      (mHMGCoA) synthase, a key control site of ketogenesis from butyrate, is lower in
      germ-free (GF) than in conventional (CV) rats. In contrast, the activity of
      glutaminase is higher. The objective of this study was to investigate whether the
      intestinal flora can affect gene expression through short chain fatty acid (SCFA)
      and butyrate production. GF rats were inoculated with a conventional flora (Ino
      CV) or with a bacterial strain producing butyrate (Clostridium paraputrificum,
      Ino-Cp) or not (Bifidobacterium breve, Ino-Bb). In the Ino-CV rats, mHMGCoA
      synthase expression was restored to the CV values 2 days after the inoculation,
      i.e. concomitantly with SCFA production. In the Ino-Cp group, but not in the Ino
      Bb group, mHMGCoA synthase and glutaminase were expressed at the level observed
      in the CV rats. These data suggest that the intestinal flora, through butyrate
      production, could control the expression of colonic mHMGCoA synthase and
      glutaminase. These modifications in gene expression by butyrate in vivo seem
      unrelated to a modification of histone acetylation.

PMID- 14686923
TI  - Protein assembly of photosystem II and accumulation of subcomplexes in the
      absence of low molecular mass subunits PsbL and PsbJ.
AB  - The protein assembly and stability of photosystem II (PSII) (sub)complexes were
      studied in mature leaves of four plastid mutants of tobacco (Nicotiana tabacum
      L), each having one of the psbEFLJ operon genes inactivated. In the absence of
      psbL, no PSII core dimers or PSII-light harvesting complex (LHCII) supercomplexes
      were formed, and the assembly of CP43 into PSII core monomers was extremely
      labile. The assembly of CP43 into PSII core monomers was found to be necessary
      for the assembly of PsbO on the lumenal side of PSII. The two other oxygen
      evolving complex (OEC) proteins, PsbP and PsbQ, were completely lacking in Delta
      psbL. In the absence of psbJ, both intact PSII core monomers and PSII core dimers
      harboring the PsbO protein were formed, whereas the LHCII antenna remained
      detached from the PSII dimers, as demonstrated by 77 K fluorescence measurements
      and by the lack of PSII-LHCII supercomplexes. The Delta psbJ mutant was
      characterized by a deficiency of PsbQ and a complete lack of PsbP. Thus, both the
      PsbL and PsbJ subunits of PSII are essential for proper assembly of the OEC. The
      absence of psbE and psbF resulted in a complete absence of all central PSII core
      and OEC proteins. In contrast, very young, vigorously expanding leaves of all
      psbEFLJ operon mutants accumulated at least traces of D2, CP43 and the OEC
      proteins PsbO and PsbQ, implying developmental control of the expression of the
      PSII core and OEC proteins. Despite severe problems in PSII assembly, the
      thylakoid membrane complexes other than PSII were present and correctly assembled
      in all psbEFLJ operon mutants.

PMID- 14686924
TI  - Volkensin from Adenia volkensii Harms (kilyambiti plant), a type 2 ribosome
      inactivating protein.
AB  - Volkensin, a type 2 ribosome-inactivating protein from the roots of Adenia
      volkensii Harms (kilyambiti plant) was characterized both at the protein and
      nucleotide level by direct amino acid sequencing and cloning of the gene encoding
      the protein. Gene sequence analysis revealed that volkensin is encoded by a 1569
      bp ORF (523 amino acid residues) without introns, with an internal linker
      sequence of 45 bp. Differences in residues present at several sequence positions
      (reproduced after repeated protein sequence analyses), with respect to the gene
      sequence, suggest several isoforms for the volkensin A-chain. Based on the
      crystallographic coordinates of ricin, which shares a high sequence identity with
      volkensin, a molecular model of volkensin was obtained. The 3D model suggests
      that the amino acid residues of the active site of the ricin A-chain are
      conserved at identical spatial positions, including Ser203, a novel amino acid
      residue found to be conserved in all known ribosome-inactivating proteins. The
      sugar binding site 1 of the ricin B-chain is also conserved in the volkensin B
      chain, whilst in binding site 2, His246 replaces Tyr248. Native volkensin
      contains two free cysteinyl residues out of 14 derived from the gene sequence,
      thus suggesting a further disulphide bridge in the B chain, in addition to the
      inter- and intrachain disulphide bond pattern common to other type 2 ribosome
      inactivating proteins.

PMID- 14686925
TI  - Determination of modulation of ligand properties of synthetic complex-type
      biantennary N-glycans by introduction of bisecting GlcNAc in silico, in vitro and
      in vivo.
AB  - We have investigated the consequences of introducing a bisecting GlcNAc moiety
      into biantennary N-glycans. Computational analysis of glycan conformation with
      prolonged simulation periods in vacuo and in a solvent box revealed two main
      effects: backfolding of the alpha1-6 arm and stacking of the bisecting GlcNAc and
      the neighboring Man/GlcNAc residues of both antennae. Chemoenzymatic synthesis
      produced the bisecting biantennary decasaccharide N-glycan and its alpha2-3(6)
      sialylated variants. They were conjugated to BSA to probe the ligand properties
      of N-glycans with bisecting GlcNAc. To assess affinity alterations in glycan
      binding to receptors, testing was performed with purified lectins, cultured
      cells, tissue sections and animals. The panel of lectins, including an
      adhesion/growth-regulatory galectin, revealed up to a sixfold difference in
      affinity constants for these neoglycoproteins relative to data on the
      unsubstituted glycans reported previously [Andre, S., Unverzagt, C., Kojima, S.,
      Dong, X., Fink, C., Kayser, K. & Gabius, H.-J. (1997) Bioconjugate Chem. 8, 845
      855]. The enhanced affinity for galectin-1 is in accord with the increased
      percentage of cell positivity in cytofluorimetric and histochemical analysis of
      carbohydrate-dependent binding of labeled neoglycoproteins to cultured tumor
      cells and routinely processed lung cancer sections. Intravenous injection of
      iodinated neoglycoproteins carrying galactose-terminated N-glycans into mice
      revealed the highest uptake in liver and spleen for the bisecting compound
      compared with the unsubstituted or core-fucosylated N-glycans. Thus, this
      substitution modulates ligand properties in interactions with lectins, a key
      finding of this report. Synthetic glycan tailoring provides a versatile approach
      to the preparation of newly substituted glycans with favorable ligand properties
      for medical applications.

PMID- 14686926
TI  - Mutations in the hydrophobic core and in the protein-RNA interface affect the
      packing and stability of icosahedral viruses.
AB  - The information required for successful assembly of an icosahedral virus is
      encoded in the native conformation of the capsid protein and in its interaction
      with the nucleic acid. Here we investigated how the packing and stability of
      virus capsids are sensitive to single amino acid substitutions in the coat
      protein. Tryptophan fluorescence, bis-8-anilinonaphthalene-1-sulfonate
      fluorescence, CD and light scattering were employed to measure urea- and pressure
      induced effects on MS2 bacteriophage and temperature sensitive mutants. M88V and
      T45S particles were less stable than the wild-type forms and completely
      dissociated at 3.0 kbar of pressure. M88V and T45S mutants also had lower
      stability in the presence of urea. We propose that the lower stability of M88V
      particles is related to an increase in the cavity of the hydrophobic core. Bis-8
      anilinonaphthalene-1-sulfonate fluorescence increased for the pressure
      dissociated mutants but not for the urea-denatured samples, indicating that the
      final products were different. To verify reassembly of the particles, gel
      filtration chromatography and infectivity assays were performed. The phage titer
      was reduced dramatically when particles were treated with a high concentration of
      urea. In contrast, the phage titer recovered after high-pressure treatment. Thus,
      after pressure-induced dissociation of the virus, information for correct
      reassembly was preserved. In contrast to M88V and T45S, the D11N mutant virus
      particle was more stable than the wild-type virus, in spite of it also possessing
      a temperature sensitive growth phenotype. Overall, our data show how point
      substitutions in the capsid protein, which affect either the packing or the
      interaction at the protein-RNA interface, result in changes in virus stability.

PMID- 14686927
TI  - Inactivation of copper-containing amine oxidases by turnover products.
AB  - For bovine serum amine oxidase, two different mechanisms of substrate-induced
      inactivation have been proposed. One consists of a slow oxidation by H2O2 of a
      conserved residue in the reduced enzyme after the fast turnover phase
      [Pietrangeli, P., Nocera, S., Fattibene, P., Wang, X.T., Mondovi, B. & Morpurgo,
      L. (2000) Biochem. Biophys. Res. Commun.267, 174-178] and the other of the
      oxidation by H2O2 of the dihydrobenzoxazole in equilibrium with the product
      Schiff base, during the catalytic cycle [Lee, Y., Shepard, E., Smith, J., Dooley,
      D.M. & Sayre, L.M. (2001) Biochemistry40, 822-829]. To discriminate between the
      two mechanisms, the inactivation was studied using Lathyrus cicera (red
      vetchling) amine oxidase. This, in contrast to bovine serum amine oxidase, formed
      the Cu+-semiquinolamine radical with a characteristic UV-vis spectrum when oxygen
      was exhausted by an excess of any tested amine in a closed cuvette. The
      inactivation, lasting about 90 min, was simultaneous with the radical decay and
      with the formation of a broad band (shoulder) at 350 nm. No inactivation occurred
      when a thousand-fold excess of amine was rapidly oxidized in an L. cicera amine
      oxidase solution stirred in open air. Thus, the inactivation is a slow reaction
      of the reduced enzyme with H2O2, following the turnover phase. Catalase protected
      L. cicera amine oxidase from inactivation. This effect was substrate-dependent,
      varying from full protection (benzylamine) to no protection (putrescine). In the
      absence of H2O2, a specific inactivating reaction, without formation of the 350
      nm band, was induced by some aldehydes, notably putrescine. Some mechanisms of
      inactivation are proposed.

PMID- 14686928
TI  - The effect of mutations surrounding and within the active site on the catalytic
      activity of ricin A chain.
AB  - Models for the binding of the sarcin-ricin loop (SRL) of 28S ribosomal RNA to
      ricin A chain (RTA) suggest that several surface exposed arginine residues
      surrounding the active site cleft make important interactions with the RNA
      substrate. The data presented in this study suggest differing roles for these
      arginyl residues. Substitution of Arg48 or Arg213 with Ala lowered the activity
      of RTA 10-fold. Furthermore, substitution of Arg213 with Asp lowered the activity
      of RTA 100-fold. The crystal structure of this RTA variant showed it to have an
      unaltered tertiary structure, suggesting that the positively charged state of
      Arg213 is crucial for activity. Substitution of Arg258 with Ala had no effect on
      activity, although substitution with Asp lowered activity 10-fold. Substitution
      of Arg134 prevented expression of folded protein, suggesting a structural role
      for this residue. Several models have been proposed for the binding of the SRL to
      the active site of RTA in which the principal difference lies in the conformation
      of the second 'G' in the target GAGA motif in the 28S rRNA substrate. In one
      model, the sidechain of Asn122 is proposed to make interactions with this G,
      whereas another model proposes interactions with Asp75 and Asn78. Site-directed
      mutagenesis of these residues of RTA favours the first of these models, as
      substitution of Asn78 with Ser yielded an RTA variant whose activity was
      essentially wild-type, whereas substitution of Asn122 reduced activity 37.5-fold.
      Substitution of Asp75 failed to yield significant folded protein, suggesting a
      structural role for this residue.

PMID- 14686929
TI  - Active-site residues and amino acid specificity of the bacterial 4'
      phosphopantothenoylcysteine synthetase CoaB.
AB  - In bacteria, coenzyme A is synthesized in five steps from d-pantothenate. The Dfp
      flavoprotein catalyzes the synthesis of the coenzyme A precursor 4'
      phosphopantetheine from 4'-phosphopantothenate and cysteine using the cofactors
      CTP and flavine mononucleotide via the phosphopeptide-like compound 4'
      phosphopantothenoylcysteine. The synthesis of 4'-phosphopantothenoylcysteine is
      catalyzed by the C-terminal CoaB domain of Dfp and occurs via the acyl-cytidylate
      intermediate 4'-phosphopantothenoyl-CMP in two half reactions. In this new study,
      the molecular characterization of the CoaB domain is continued. In addition to
      the recently described residue Asn210, two more active-site residues, Arg206 and
      Ala276, were identified and shown to be involved in the second half reaction of
      the (R)-4'-phospho-N-pantothenoylcysteine synthetase. The proposed intermediate
      of the (R)-4'-phospho-N-pantothenoylcysteine synthetase reaction, 4'
      phosphopantothenoyl-CMP, was characterized by MALDI-TOF MS and it was shown that
      the intermediate is copurified with the mutant His-CoaB N210H/K proteins.
      Therefore, His-CoaB N210H and His-CoaB N210K will be of interest to elucidate the
      crystal structure of CoaB complexed with the reaction intermediate. Wild-type His
      CoaB is not absolutely specific for cysteine and can couple derivatives of
      cysteine to 4'-phosphopantothenate. However, no phosphopeptide-like structure is
      formed with serine. Molecular characterization of the temperature-sensitive
      Escherichia coli dfp-1 mutant revealed that the residue adjacent to Ala276,
      Ala275 of the strictly conserved AAVAD(275-279) motif, is exchanged for Thr.

PMID- 14686930
TI  - Numerical calculations of the pH of maximal protein stability. The effect of the
      sequence composition and three-dimensional structure.
AB  - A large number of proteins, found experimentally to have different optimum pH of
      maximal stability, were studied to reveal the basic principles of their
      preference for a particular pH. The pH-dependent free energy of folding was
      modeled numerically as a function of pH as well as the net charge of the protein.
      The optimum pH was determined in the numerical calculations as the pH of the
      minimum free energy of folding. The experimental data for the pH of maximal
      stability (experimental optimum pH) was reproducible (rmsd = 0.73). It was shown
      that the optimum pH results from two factors - amino acid composition and the
      organization of the titratable groups with the 3D structure. It was demonstrated
      that the optimum pH and isoelectric point could be quite different. In many
      cases, the optimum pH was found at a pH corresponding to a large net charge of
      the protein. At the same time, there was a tendency for proteins having acidic
      optimum pHs to have a base/acid ratio smaller than one and vice versa. The
      correlation between the optimum pH and base/acid ratio is significant if only
      buried groups are taken into account. It was shown that a protein that provides a
      favorable electrostatic environment for acids and disfavors the bases tends to
      have high optimum pH and vice versa.

PMID- 14686931
TI  - Suppression of beta 1,3galactosyltransferase beta 3Gal-T5 in cancer cells reduces
      sialyl-Lewis a and enhances poly N-acetyllactosamines and sialyl-Lewis x on O
      glycans.
AB  - We investigated the role of beta 3 Gal-T5, a member of the beta
      1,3galactosyltransferase (beta 1,3Gal-T) family, in cancer-associated
      glycosylation, focusing on the expression of sialyl-Lewis a (sLea, the epitope of
      CA19.9 antigen), poly N-acetyllactosamines, and sialyl-Lewis x (sLex) antigen. A
      clone permanently expressing an antisense fragment of beta 3Gal-T5 was obtained
      from the human pancreas adenocarcinoma cell line BxPC3 and characterized. Both
      beta 1,3Gal-T activity and sLea expression are dramatically impaired in the
      clone. Analysis of the oligosaccharides synthesized in cells metabolically
      labelled with tritiated galactose shows that a relevant amount of radioactivity
      is associated to large O-glycans. Endo-beta-galactosidase mostly releases NeuAc
      alpha 2-3Gal beta 1-3[Fuc alpha 1-4]GlcNAc beta 1-3Gal and NeuAc alpha 2-3Gal
      beta 1-3GlcNAc beta 1-3Gal from such O-glycans of BxPC3 membranes, but GlcNAc
      beta 1-3Gal and type 2 chain oligosaccharides, including NeuAc alpha 2-3Gal beta
      1-4[Fuc alpha 1-3]GlcNAc beta 1-3Gal, from those of the antisense clone.
      Furthermore, BxPC3 cells secrete sLea in the culture media but not sLex, while
      antisense clone secretes mostly sLex, and accumulation of both antigens is
      prevented by benzyl-alpha-GalNAc. These data indicate that beta 3Gal-T5
      suppression turns synthesis of type 1 chain O-glycans to poly N-acetyllactosamine
      elongation and termination by sLex. In other cell lines and clones, beta 3Gal-T5
      transcript, beta 1,3Gal-T activity, and sLea antigen are also correlated, but
      quantitatively the relative expression ratios are very different from cell type
      to cell type. We suggest that beta 3Gal-T5 plays a relevant role in
      gastrointestinal and pancreatic tissues counteracting the glycosylation pattern
      associated to malignancy, and is necessary for the synthesis and secretion of
      CA19.9 antigen, whose expression still depends on multiple interacting factors.

PMID- 14686932
TI  - UV-A/blue-light inactivation of the 'metal-free' hydrogenase (Hmd) from
      methanogenic archaea.
AB  - H2-forming methylenetetrahydromethanopterin dehydrogenase (Hmd) is an unusual
      hydrogenase present in many methanogenic archaea. The homodimeric enzyme dubbed
      'metal-free' hydrogenase does not contain iron-sulfur clusters or nickel and thus
      differs from [Ni-Fe] and [Fe-Fe] hydrogenases, which are all iron-sulfur
      proteins. Hmd preparations were found to contain up to 1 mol iron per 40 kDa
      subunit, but the iron was considered to be a contaminant as none of the catalytic
      and spectroscopic properties of the enzyme indicated that it was an essential
      component. Hmd does, however, harbour a low molecular mass cofactor of yet
      unknown structure. We report here that the iron found in Hmd is most probably
      functional after all. Further investigation was initiated by the discovery that
      Hmd is inactivated upon exposure to UV-A (320-400 nm) or blue-light (400-500 nm).
      Enzyme purified in the dark exhibited an absorption spectrum with a maximum at
      approximately 360 nm and which mirrored its sensitivity towards light. In UV
      A/blue-light the enzyme was bleached. The cofactor extracted from active Hmd was
      also light sensitive. It showed an UV/visible spectrum similar to that of the
      active enzyme and was bleached upon exposure to light. Photobleached cofactor no
      longer had the ability to reconstitute active Hmd from the apoenzyme. When
      purified in the dark, Hmd consistently contained per monomer about one Fe, which
      was tightly bound to the cofactor. The iron was released from the enzyme and from
      the cofactor upon light inactivation. Hmd activity was inhibited by high
      concentrations of CO and CO protected the enzyme from light inactivation
      indicating that the iron in Hmd is of functional importance. Therefore, reference
      to Hmd as 'metal-free' hydrogenase is no longer appropriate.

PMID- 14686933
TI  - HIV-1 integrase can process a 3'-end crosslinked substrate.
AB  - Integrase of the human immunodeficiency virus type-1 (HIV-1) recognizes specific
      sequences located in the U3 and U5 regions at the ends of viral DNA. We
      synthesized DNA duplexes mimicking the U5 region and containing either 2'
      aminonucleosides or non-nucleoside 1,3-propanediol insertions at the third and
      terminal positions and studied their interactions with HIV-1 integrase. Both
      modifications introduced a local structural distortion in the DNA double helix.
      Replacement of the terminal nucleosides by corresponding 2'-aminonucleosides had
      no significant effect on integrase activity. We used an integrase substrate
      bearing terminal 2'-aminonucleosides in both strands to synthesize a duplex with
      cross-linked strands. This duplex was then used to determine whether terminal
      base pair disruption is an obligatory step of retroviral DNA 3'-processing.
      Processing of the cross-linked analog of the integrase substrate yielded a
      product of the same length as 3'-processing of the wild-type substrate but the
      reaction efficiency was lower. Replacement of the third adenosine in the
      processed strand by a corresponding 2'-aminonucleoside did not affect integrase
      activity, whereas, its replacement by 1,3-propanediol completely inhibited 3'
      processing. Both modifications of the complementary thymidine in the nonprocessed
      strand increased the initial rate of 3'-processing. The same effect was observed
      when both nucleosides, at the third position, were replaced by corresponding 2'
      aminonucleosides. This indicates that the local duplex distortion facilitated the
      cleavage of the phosphodiester bond. Thus, a localized destabilization of the
      third A-T base pair is necessary for efficient 3'-processing, whereas 3'-end
      fraying is important but not absolutely required.

PMID- 14686934
TI  - Tungsten-containing aldehyde oxidoreductase of Eubacterium acidaminophilum.
AB  - Aldehyde oxidoreductase of Eubacterium acidaminophilum was purified to
      homogeneity under strict anaerobic conditions using a four-step procedure. The
      purified enzyme was present as a monomer with an apparent molecular mass of 67
      kDa and contained 6.0 +/- 0.1 iron, 1.1 +/- 0.2 tungsten, about 0.6 mol pterin
      cofactor and zinc, but no molybdenum. The enzyme activity was induced if a molar
      excess of electron donors, such as serine and/or formate, were supplied in the
      growth medium compared to readily available electron acceptors such as glycine
      betaine. Many aldehydes served as good substrates, thus enzyme activity obtained
      with acetaldehyde, propionaldehyde, butyraldehyde, isovaleraldehyde and
      benzaldehyde differed by a factor of less than two. Kinetic parameters were
      determined for all substrates tested. Oligonucleotides deduced from the N
      terminal amino acid sequence were used to isolate the encoding aorA gene and
      adjacent DNA regions. The deduced amino acid sequence of the aldehyde
      oxidoreductase exhibited high similarities to other tungsten-containing aldehyde
      oxidoreductases from archaea. Transcription of the aorA gene was monocistronic
      and started from a sigma 54-dependent promoter. Upstream of aorA, the gene aorR
      is localized whose product is similar to sigma 54-dependent transcriptional
      activator proteins and, thus, AorR is probably involved in the regulation of aorA
      expression.

PMID- 14686935
TI  - Damped oscillatory hysteretic behaviour of butyrylcholinesterase with
      benzoylcholine as substrate.
AB  - Steady-state kinetics for the hydrolysis of benzoylcholine (BzCh) and
      benzoylthiocholine (BzSCh) by wild-type human butyrylcholinesterase (BuChE) and
      by the peripheral anionic site mutant D70G were compared. kcat/Km for the
      hydrolysis of BzSCh was 17-fold and 32-fold lower than that for hydrolysis of
      BzCh by wild-type and D70G, respectively. The rate-limiting step for hydrolysis
      of BzCh was deacylation, whereas acylation was rate-limiting for hydrolysis of
      BzSCh. Wild-type enzyme and the D70G mutant were found to reach steady-state
      velocity slowly with BzCh as the substrate. At pH 6, the approach to steady-state
      for both enzymes consisted of a mono-exponential acceleration upon which a set of
      damped oscillations was superimposed. From pH 7 to 8.5, the approach to steady
      state consisted of a simple exponential acceleration. The damped oscillations
      were analyzed by both a numerical approximation and simulation based on a
      theoretical model. BuChE-catalyzed hydrolysis of the thiocholine analogue of BzCh
      showed neither lags nor oscillations, under the same conditions. The frequency
      and amplitude of the damped oscillations decreased as the BzCh concentration
      increased. The apparent induction time for the exponential portion of the lag was
      calculated from the envelope of the damped oscillations or from the smooth lag.
      Wild-type BuChE showed a hyperbolic increase in induction time as the BzCh
      concentration increased (tau max = 210 s at pH 6.0). However, the induction time
      for D70G was constant over the whole range of BzCh concentrations (tau max = 60 s
      at pH 6.0). Thus, the induction time does not conform to a simple hysteretic
      model in which there is a slow conformational transition of the enzyme from an
      inactive form E to an active form E'. No pH-dependence of the induction time was
      found between pH 6.0 and 8.5 in sodium phosphate buffers of various
      concentrations (from 1 mm to 1 m). However, increasing the pH tended to abolish
      the oscillations (increase the damping factor). This effect was more pronounced
      for D70G than for wild-type. Although the lyotropic properties of phosphate
      change from chaotropic at pH 6.0 to kosmotropic at pH > 8.0, no effect of
      phosphate concentration on the oscillations was noticed at the different pH
      values, suggesting that the oscillations are not related to a pH-dependent
      Hofmeister effect of phosphate ions. Simulation and theoretical analysis of the
      oscillatory behaviour of the approach to the steady-state for BuChE led us to
      propose a model for the hysteresis of BuChE with BzCh. In this model, the
      substrate-free enzyme is present as an equilibrium mixture of two forms, E and
      E'. Substrate binds to E and E', but only Epsilon'S makes products. It is
      proposed that oscillations originate from a time-dependent change in the local
      concentration, solvation and/or conformation of substrate in the bulk solution.
      1H-NMR measurements provided evidence for a slow equilibrium between two BzCh
      conformers. Binding of the conformationally preferred substrate conformer leads
      to products.

PMID- 14686936
TI  - Are viruses driving microbial diversification and diversity?
AB  - Viruses can influence the genetic diversity of prokaryotes in various ways. They
      can affect the community composition of prokaryotes by 'killing the winner' and
      keeping in check competitive dominants. This may sustain species richness and the
      amount of information encoded in genomes. Viruses can also transfer (viral and
      host) genes between species. Such mechanisms have probably influenced the
      speciation of prokaryotes. Whole-genome sequencing has clearly revealed the
      importance of (virus-mediated) gene transfer. However, its significance for the
      ecological performance of aquatic microbial communities is only poorly studied,
      although the few available reports indicate a large potential. Here, we present
      data supporting the hypothesis that viral genes and viral activity generate
      genetic variability of prokaryotes and are a driving force for ecological
      functioning and evolutionary change.

PMID- 14686937
TI  - Plastic phenotypic resistance to predation by Bdellovibrio and like organisms in
      bacterial prey.
AB  - Predation at the lowest trophic level, i.e. between bacteria, is poorly
      understood, hindering efforts to assess its impact on the structure of bacterial
      communities. The interaction of Bdellovibrio and Bacteriovorax (Bdellovibrio and
      like organisms, BLOs), a group of obligate, ubiquitous predatory bacteria, with
      their Gram-negative bacterial prey results in the multiplication of the predator
      and in the lysis, but not in the eradication, of the prey. We show that the
      residual, surviving populations of prey cells exposed to predation stress differ
      from the populations before exposure, as they exhibit increased resistance to
      predation. This resistance was demonstrated in a number of Gram-negative prey.
      Moreover, predation resistance is not specific for the BLO strain experienced by
      the prey. The phenomenon does not stem from a mutation but is a plastic response
      associated with a phenotypic change, and it disappears upon removal of the
      predator. As resistance to predation is not total, this mechanism can ensure
      survival of both predator and prey.

PMID- 14686938
TI  - Comparative analysis of a genome fragment of an uncultivated mesopelagic
      crenarchaeote reveals multiple horizontal gene transfers.
AB  - Marine planktonic crenarchaeota have escaped all cultivation attempts to date,
      all crenarchaeota growing in pure culture so far being hyperthermophiles. Here,
      we present a comparative genomic analysis of a 16S- plus 23S-rDNA-containing
      fragment of a crenarchaeote retrieved from an environmental genomic library
      constructed from picoplankton collected at 500 m depth in the Antarctic Polar
      Front. The clone DeepAnt-EC39 contained an insert of 33.3 kbp, which was
      completely sequenced. DeepAnt-EC39 appears to represent a lineage specific to
      deep-sea waters but widespread geographically, as revealed by the analysis of the
      16S-23S-rDNA intergenic spacer region. A comparison with previously sequenced
      marine crenarchaeotal genomic clones also containing an rrn operon (74A4, 4B7 and
      Cenarchaeum symbiosum strains A and B) revealed a highly variable structure
      involving gene rearrangements and insertions/deletions. The surroundings of the
      rrn operon and the contiguous glutamate-1-semialdehyde aminotransferase gene
      appear hot spots for recombination. Phylogenetic analyses of all individual
      predicted proteins revealed the existence of several likely cases of horizontal
      gene transfer both, between the two archaeal kingdoms and between the two
      prokaryotic domains. The most frequent horizontal transfers appear to involve
      genes from mesophilic methanogenic euryarchaeota related to Methanosarcinales. We
      hypothesise that the acquisition of genes from mesophilic bacteria and
      euryarchaeota has played a major role in the adaptation of Group I crenarchaeota
      to life at lower temperatures.

PMID- 14686939
TI  - Detection and phylogenetic analysis of Wolbachia in Collembola.
AB  - Wolbachia are obligatory, cytoplasmatically inherited alpha-Proteobacteria which
      are known for infecting the reproductive tissues of many arthropods. Their
      prevalence in the large group of Collembola, however, is not known, except for
      PCR detection in the parthenogenetically reproducing species Folsomia candida
      (Order: Entomobryomorpha; Family: Isotomidae). In this study, fluorescence in
      situ hybridization on microscopic sections of F. candida specimens indicated that
      Wolbachia-related bacteria were restricted to tissues of the ovary and brain. PCR
      with primers designed to detect 16S rRNA genes of Wolbachia were positive with
      specimens from all of five geographically independent F. candida breeding stocks
      and with three parthenogenetic species from another order (Poduromorpha; Family
      Tullbergiidae), i.e. Mesaphorura italica, M. macrochaeta and Paratullbergia
      callipygos. In contrast, negative results were obtained with the two sexually
      reproducing species, Isotoma viridis (Isotomidae) and Protaphorura fimata
      (Poduromorpha; Onychiuridae). The ftsZ gene of Wolbachia could be PCR-amplified
      from all Wolbachia-positive hosts with the exception of M. macrochaeta. The
      phylogenetic distances of the ftsZ and 16S rRNA gene sequences reflected the
      phylogenetic distances of the host organisms but the sequences of Wolbachia were
      relatively closely related, indicating that Wolbachia infections took place after
      the Collembola had diversified. Our study confirms a monophyletic branch
      (supergroup E) of Collembola colonizing Wolbachia and indicates that this group
      is a sister group of supergroup A, the latter harbouring a high diversity of host
      organisms within the group of insects.

PMID- 14686940
TI  - Analysis and comparison of the microbial community structures of two enrichment
      cultures capable of reductively dechlorinating TCE and cis-DCE.
AB  - In order to study the effect of different chloroethenes (electron acceptors) on
      the bacterial composition of dechlorinating communities, two reductive
      dechlorinating enrichment cultures were developed that were able to reduce
      trichloroethene (TCE) and cis-1,2-dichloroethene (cis-DCE) to ethene using
      hydrogen as electron donor, respectively. The inoculum for the cultures was
      material from a methanogenic fluidized bed reactor (FBR), which was originally
      seeded with digester sludge and showed a stable capacity for tetrachloroethene
      (PCE) reduction to ethene for over six years. Molecular methods were used to
      determine and compare the microbial communities of these two enrichment cultures.
      A clone library of bacterial 16S rRNA genes was generated for each enrichment.
      The clones were screened into different groups by restriction fragment length
      polymorphism (RFLP) analysis using two different four base pair recognition
      restriction enzymes. A total of 12 sequence types were identified by phylogenetic
      analysis of nearly complete 16S rDNA sequences ( approximately 1450 bp). The
      sequences were affiliated with six recognized phyla of the domain Bacteria:
      Firmicutes (low G+C Gram-positives), Chloroflexi (green non-sulphur bacteria),
      Actinobacteria (high G+C Gram-positives), Bacteroidetes (Cytophaga-Flexibacter
      Bacteroides), Nitrospira and Spirochaetes. The results led to the identification
      of an organism closely related to Dehalococcoides ethenogenes to be the
      presumptive dechlorinator in both enrichments. Different electron acceptors
      affected the bacterial diversity and the community profiles of the two
      enrichments. Most of the sequences identified in our dechlorinating enrichments
      shared high similarities with sequences previously obtained from other enriched
      dechlorinating cultures and chlorinated-compound-contaminated sediments or
      aquifers, suggesting these bacteria may have direct or indirect roles in
      reductive dechlorination.

PMID- 14686941
TI  - Evidence for transmission between humans and the environment of a nosocomial
      strain of Enterococcus faecium.
AB  - An ampicillin- and ciprofloxacin-resistant Enterococcus faecium (ARE) strain,
      named FMSE1, with a characteristic biochemical phenotype, was in a recent study
      found to dominate among faecal ARE isolates from patients in several Swedish
      hospitals. In the present study, the prevalence of this strain among 9676
      enterococcal isolates from healthy children, hospital sewage, urban sewage,
      surface water, slaughtered animals (broilers, pigs and cattle) and pig faeces and
      manure was investigated. Enterococcal isolates having the same biochemical
      phenotype as the FMSE1 were most common in samples of hospital sewage (50%),
      surface water (35%), treated sewage (28%) and untreated sewage (17%), but rare in
      samples from healthy children (0.8%) and animals (2%). PFGE typing of FMSE1-like
      isolates from hospital sewage indicated that they were closely related to the
      nosocomial FMSE1 strain. Thus, this study indicated a possible transmission route
      for nosocomial E. faecium from patients in hospitals to hospital sewage and urban
      sewage, and further via treatment plants to surface water and possibly back to
      humans. This proposed route of circulation of drug-resistant enterococci might be
      further amplified by antibiotic usage in human medicine. In contrast, such
      transmission from food animals seems to play a negligible role in Sweden.

PMID- 14686942
TI  - Stable isotope probing of rRNA and DNA reveals a dynamic methylotroph community
      and trophic interactions with fungi and protozoa in oxic rice field soil.
AB  - Stable isotope probing (SIP) is a novel technique to characterize structure and
      in situ function of active microbial populations, which is based on the
      incorporation of 13C-labelled substrates into nucleic acids. Here, we have traced
      methylotrophic members of a rice field soil microbial community, which became
      active upon continuous addition of 13C-methanol (< 22 mM) as studied in
      microcosms. By combining rRNA- and DNA-based SIP, as well as domain-specific real
      time PCR detection of templates in fractions of centrifugation gradients, we were
      able to detect 13C-labelled bacterial rRNA after 6 days of incubation.
      Fingerprinting and comparative sequence analysis of 'heavy' bacterial rRNA showed
      that mostly members of the Methylobacteriaceae and a novel clade within the
      Methylophilaceae formed part of the indigenous methylotrophic community. Over
      time, however, the Methylophilaceae were enriched. Unexpectedly, nucleic acids of
      eukaryotic origin were detected, mostly in intermediately 13C-labelled gradient
      fractions. These eukaryotes were identified as fungi mostly related to Fusarium
      and Aspergillus spp., and also Cercozoa, known as predatory soil flagellates. The
      detection of fungi and protozoa in 13C-enriched nucleic acid fractions suggests a
      possible involvement in either direct assimilation of label by the fungi, or a
      food web, i.e. that primary 13C-methanol consuming methylotrophs were decomposed
      by fungi and grazed by protozoa.

PMID- 14686943
TI  - Enhanced sensitivity of DNA- and rRNA-based stable isotope probing by
      fractionation and quantitative analysis of isopycnic centrifugation gradients.
AB  - Stable isotope probing (SIP) of nucleic acids allows the detection and
      identification of active members of natural microbial populations that are
      involved in the assimilation of an isotopically labelled compound into nucleic
      acids. SIP is based on the separation of isotopically labelled DNA or rRNA by
      isopycnic density gradient centrifugation. We have developed a highly sensitive
      protocol for the detection of 'light' and 'heavy' nucleic acids in fractions of
      centrifugation gradients. It involves the fluorometric quantification of total
      DNA or rRNA, and the quantification of either 16S rRNA genes or 16S rRNA in
      gradient fractions by real-time PCR with domain-specific primers. Using this
      approach, we found that fully 13C-labelled DNA or rRNA of Methylobacterium
      extorquens was quantitatively resolved from unlabelled DNA or rRNA of
      Methanosarcina barkeri by cesium chloride or cesium trifluoroacetate density
      gradient centrifugation respectively. However, a constant low background of
      unspecific nucleic acids was detected in all DNA or rRNA gradient fractions,
      which is important for the interpretation of environmental SIP results.
      Consequently, quantitative analysis of gradient fractions provides a higher
      precision and finer resolution for retrieval of isotopically enriched nucleic
      acids than possible using ethidium bromide or gradient fractionation combined
      with fingerprinting analyses. This is a prerequisite for the fine-scale tracing
      of microbial populations metabolizing 13C-labelled compounds in natural
      ecosystems.

PMID- 14686944
TI  - Competitive interactions between Microdochium nivale var. majus, M. nivale var.
      nivale and Fusarium culmorum in planta and in vitro.
AB  - Microdochium nivale var. majus and var. nivale are economically important fungal
      pathogens of cereal seedlings, stem bases and ears, as is the toxigenic species
      Fusarium culmorum. Competition experiments on seedlings support an earlier report
      of differential host preference between the varieties of M. nivale on wheat and
      rye seedlings at 15 degrees C, but showed that it does not extend across a broad
      range of temperatures. The studies showed that, although interaction is
      disadvantageous to the less virulent pathogen, it does not confer an advantage to
      the more virulent pathogen. In mixed inoculum experiments on wheat seedlings at
      15 degrees C and 20 degrees C, F. culmorum suppressed the growth of both
      varieties of M. nivale. However, if M. nivale var. majus became established on
      the seedlings, it was able to co-suppress colonization of wheat seedlings by F.
      culmorum. In contrast M. nivale var. nivale did not suppress F. culmorum
      significantly. The growth of M. nivale var. majus and F. culmorum was also co
      suppressed in liquid culture. Significantly, the accumulation of deoxynivalenol
      mycotoxin was also reduced in the mixed in vitro culture compared with axenic
      culture of F. culmorum. However, in vitro interaction studies on solidified media
      were of only limited use in predicting the outcome of competitions in planta.

PMID- 14686945
TI  - Plant-dependent active biological containment system for recombinant
      rhizobacteria.
AB  - This work describes the construction of the rhizobacterium Pseudomonas putida
      strain CS-4, which contains an active biological containment (ABC) system that
      ensures bacterial suicide in the absence of proline. Maize plants exudate
      proline, which allows CS-4 to colonize the rhizosphere at a similar level to that
      of the wild-type strain. However, when the plants are removed, the CS-4
      population decreased in bulk soil at a higher rate than the wild-type strain.

PMID- 14686949
TI  - Four-dimensional imaging of cytoskeletal dynamics in Xenopus oocytes and eggs.
AB  - The Xenopus laevis (African clawed frog) system has long been popular for studies
      of both developmental and cell biology, based on a variety of its intrinsic
      features including the large size of Xenopus oocytes, eggs, and embryos, and the
      relative ease of manipulation. Unfortunately, the large size has also been
      considered a serious impediment for high-resolution light microscopy, as has the
      heavy pigmentation. However, the recent development and exploitation of 4D
      imaging approaches, and the fact that much of what is of most interest to cell
      and developmental biologists takes place near the cell surface, indicates that
      such concerns are no longer valid. Consequently, the Xenopus system in many
      respects is now as good as other model systems considered to be ideal for
      microscopy-based studies. Here, 4D imaging and its recent applications to
      cytoskeletal imaging in Xenopus oocytes and eggs are discussed.

PMID- 14686950
TI  - Protein localization in living cells and tissues using FRET and FLIM.
AB  - Interacting proteins assemble into molecular machines that control cellular
      homeostasis in living cells. While the in vitro screening methods have the
      advantage of providing direct access to the genetic information encoding unknown
      protein partners, they do not allow direct access to interactions of these
      protein partners in their natural environment inside the living cell. Using wide
      field, confocal, or two-photon (2p) fluorescence resonance energy transfer (FRET)
      microscopy, this information can be obtained from living cells and tissues with
      nanometer resolution. One of the important conditions for FRET to occur is the
      overlap of the emission spectrum of the donor with the absorption spectrum of the
      acceptor. As a result of spectral overlap, the FRET signal is always contaminated
      by donor emission into the acceptor channel and by the excitation of acceptor
      molecules by the donor excitation wavelength. Mathematical algorithms are
      required to correct the spectral bleed-through signal in wide-field, confocal,
      and two-photon FRET microscopy. In contrast, spectral bleed-through is not an
      issue in FRET/FLIM imaging because only the donor fluorophore lifetime is
      measured; also, fluorescence lifetime imaging microscopy (FLIM) measurements are
      independent of excitation intensity or fluorophore concentration. The combination
      of FRET and FLIM provides high spatial (nanometer) and temporal (nanosecond)
      resolution when compared to intensity-based FRET imaging. In this paper, we
      describe various FRET microscopy techniques and its application to protein
      protein interactions.

PMID- 14686951
TI  - Quantum dot-based cell motility assay.
AB  - Motility and migration are measurable characteristics of cells that are
      classically associated with the invasive potential of cancer cells, but in vitro
      assays of invasiveness have been less than perfect. We previously developed an
      assay to monitor cell motility and migration using water-soluble CdSe/ZnS
      nanocrystals; cells engulf the fluorescent nanocrystals as they crawl across them
      and leave behind a fluorescent-free trail. We show here that semiconductor
      nanocrystals can also be used as a sensitive two-dimensional in vitro invasion
      assay. We used this assay to compare the behavior of seven different adherent
      human cell lines, including breast epithelial MCF 10A, breast tumor MDA-MB-231,
      MDA-MB-435S, MCF 7, colon tumor SW480, lung tumor NCI H1299, and bone tumor Saos
      2, and observed two distinct behaviors of cancer cells that can be used to
      further categorize these cells. Some cancer cell lines demonstrate fibroblastic
      behaviors and leave long fluorescent-free trails as they migrate across the dish,
      whereas other cancer cells leave clear zones of varying sizes around their
      periphery. This assay uses fluorescence detection, requires no processing, and
      can be used in live cell studies. These features contribute to the increased
      sensitivity of this assay and make it a powerful new tool for discriminating
      between non-invasive and invasive cancer cell lines.

PMID- 14686952
TI  - Mitochondrial differentiation in kinetoplastid protozoa: a plethora of RNA
      controls.
AB  - Differentiation of kinetoplastid protozoa during their complex life cycles is
      accompanied by stepwise changes in mitochondrial functions. Recent studies have
      begun to reveal multilevel post-transcriptional regulatory mechanisms by which
      the expression of the nuclear and mitochondrially encoded components of
      respiratory enzymes is coordinated, as well as the identities of some general and
      gene-specific factors controlling mitochondrial differentiation.

PMID- 14686953
TI  - Temporal and spatial expression of ammonium transporter genes during growth and
      development of Dictyostelium discoideum.
AB  - Ammonia is an important signaling molecule involved in the regulation of
      development in Dictyostelium. During aggregation, ammonia gradients are
      established, and the ammonia concentration in the immediate environment or within
      a particular cell throughout development may vary. This is due to the rate of
      cellular ammonia production, its rate of loss by evaporation to the atmosphere or
      by diffusion into the substratum, and perhaps to cellular transport by ammonium
      transporters (AMTs). Recent efforts in genome and cDNA sequencing have identified
      three ammonium transporters in Dictyostelium. In addition to physically altering
      the levels of ammonia within cells, AMTs also may play a role in ammonia
      signaling. As an initial step in identifying such a function, the temporal and
      spatial expression of the three amt genes is examined. RT-PCR demonstrates that
      each of the three amt mRNAs is present and relatively constant throughout growth
      and development. The spatial expression of these three amt genes is examined
      during multiple stages of Dictyostelium development using in situ hybridization.
      A distinct and dynamic pattern of expression is seen for the three genes. In
      general, amtA is expressed heavily in pre-stalk cells in a dynamic way, while
      amtB and amtC are expressed in pre-spore regions consistently throughout
      development. AmtC also is expressed in the most anterior tip of fingers and
      slugs, corresponding to cells that mediate ammonia's effect on the choice between
      slug migration and culmination. Indeed, amtC null cells have a slugger phenotype,
      suggesting AmtC functions in the signaling pathway underlying the mechanics of
      this choice.

PMID- 14686954
TI  - BMP2 initiates chondrogenic lineage development of adult human mesenchymal stem
      cells in high-density culture.
AB  - Human bone marrow-derived mesenchymal stem cells (MSCs) have been shown to
      differentiate into distinct mesenchymal tissues including bone and cartilage. The
      capacity of MSCs to replicate undifferentiated and to mature into cartilaginous
      tissues suggests these cells as an attractive cell source for cartilage tissue
      engineering. Here we show that the stimulation of human bone marrow-derived MSCs
      with recombinant bone morphogenetic protein-2 (BMP2) results in chondrogenic
      lineage development under serum-free conditions. Histological staining of
      proteoglycan with Alcian blue and immunohistochemical staining of cartilage
      specific type II collagen revealed the deposition of typical cartilage
      extracellular matrix components. Semi-quantitative real-time gene expression
      analysis of characteristic chondrocytic matrix genes, such as cartilage link
      protein, cartilage oligomeric matrix protein, aggrecan, and types I, II, and IX
      collagen, confirmed the induction of the chondrocytic phenotype in high-density
      culture upon stimulation with BMP2 and transforming growth factor-beta3
      (TGFbeta3). Histologic staining of mineralized extracellular matrix with von
      Kossa, immunostaining of type X collagen (typical for hypertrophic chondrocytes),
      and gene expression analysis of osteocalcin and adipocyte-specific fatty acid
      binding protein (aP2) further documented that BMP2 induced chondrogenic lineage
      development and not osteogenesis and/or adipogenesis in human MSCs. These results
      suggest BMP2 as a promising candidate for tissue engineering approaches
      regenerating articular cartilage on the basis of mesenchymal progenitors from
      bone marrow.

PMID- 14686956
TI  - Lipoprotein lipase gene variants and the effect of environmental factors on
      cardiovascular disease risk.
AB  - Coronary heart disease (CHD) is a major cause of mortality in the Western world.
      CHD risk is known to be modified by both genetic and environmental factors. In
      this review, we look at the role of lipoprotein lipase (LPL) gene variants in
      predisposing to CHD risk and the important interaction between these genotypes
      and environmental factors (e.g. smoking). Gene-environmental interactions result
      in a greater than additive effect on risk and understanding these gene
      environmental interactions has the potential not only for improving our
      understanding of the pathophysiology of the disease, but also in the development
      of new therapies and the targeting of specific therapies. For example, if a
      genotype increases risk in a particular environment, then those subjects would be
      encouraged to change their lifestyles more aggressively. Similarly at-risk
      subjects could be targeted with available therapies more appropriately.

PMID- 14686955
TI  - Limb bud progenitor cells induce differentiation of pluripotent embryonic stem
      cells into chondrogenic lineage.
AB  - Pluripotent embryonic stem (ES) cells are the most versatile cells, with the
      potential to differentiate into all types of cells. However, the cellular and
      molecular mechanisms responsible for their differentiation into specific lineages
      have not been elucidated. Recent studies in human ES cells have challenged the
      scientific community to focus research on the basic mechanisms of stem cell
      differentiation for their potential applications in regenerative medicine and
      cell-based therapies. The majority of studies thus far have focused on cells that
      are already committed to specific lineages. The current studies were designed to
      establish a system for investigating the mechanisms of cell fate determination
      starting from undifferentiated ES cells, to gain insight into events during the
      normally inaccessible period of development. Here we demonstrate that pluripotent
      ES cells can be programmed to differentiate into chondrocytes, the cartilage
      producing cells, by co-culture with progenitor cells from the limb buds of the
      developing embryo. Almost 60%-80% of the cells exhibited phenotypic
      characteristics of mature chondrocytes and expressed genes such as sox9, collagen
      type II, and proteoglycans, which was accompanied by a decrease in ES cell
      specific transcription factor Oct-4. Collagen type II, which is expressed in two
      different forms during chondrogenic differentiation due to the alternate splicing
      of mRNA, was also properly regulated. The studies presented here suggest that the
      signals produced by progenitor cells from the developing embryo can induce
      lineage-specific differentiation. The system described here may serve as an in
      vitro model to study the mechanisms of cell fate determination by stem cells.

PMID- 14686957
TI  - Effects of short-term metformin treatment on insulin sensitivity of blood glucose
      and free fatty acids.
AB  - AIM: Based on the known effect of metformin (MET) in improving insulin
      sensitivity in type 2 diabetes, with the scope to focus the effects on glycaemic
      and free fatty acids (FFA) levels, we studied the effects of a short-term
      treatment with this drug in obese subjects and obese patients with diabetes or
      family history of diabetes (FHD). We used a method to allow us to evaluate the
      possible difference of insulin sensibility with regard to the insulin action on
      glycaemia and blood FFA, both in the basal state and during oral glucose
      tolerance test (OGTT). METHODS: Insulin sensitivity was investigated before and
      after MET treatment (850 mg bid for 10 days) in seven obese subjects with normal
      glucose tolerance and without FHD and 13 obese patients with diabetes (n=7) or
      FHD (n=6). By using specifically designed formulae, we calculated four insulin
      sensitivity indices (ISI) from basal level (b) and area values (a) (during OGTT)
      of insulinaemia, glycaemia (gly) or FFA (ffa), namely: ISI (gly)-b, ISI (gly)-a,
      ISI (ffa)-b and ISI (ffa)-a. RESULTS: In patients with diabetes or FHD, MET
      improved ISI (gly)-b (0.79 +/- 0.06 vs. 0.59 +/- 0.07, p<0.001) and ISI (gly)-a
      (0.69 +/- 0.09 vs. 0.51 +/- 0.07, p<0.05), whereas only minor changes occurred
      for ISI (ffa)-b and ISI (ffa)-a. In contrast, in simple obese subjects, MET
      induced further deterioration of both ISI (gly)-a (0.47 +/- 0.07 vs. 0.64 +/-
      0.10, p<0.01) and ISI (ffa)-a (0.43 +/- 0.07 vs. 0.55 +/- 0.08, p<0.05). Fasting
      level and total area of lactate were high in the obese patients and were not
      affected by MET. A statistically significant increase (p<0.01), however, was
      observed for the 'decremental' area of lactate in obese subjects with diabetes or
      FHD, which might probably contribute to the reduction of insulin resistance
      induced by the drug in these patients. CONCLUSIONS: Although the low number of
      subjects studied precludes absolute conclusions, data would suggest that MET
      improved ISI towards glucose but not towards FFA, in the diabetic and
      'prediabetic' obese patients, whereas worsened it in the obese subjects without
      FHD. Therefore, the effects of MET would not be secondary to changes of FFA but
      rather to a primary action of MET on glucose metabolism. Thus, utilization of MET
      to treat the insulin resistance in obesity is indicated only in the presence of
      alterations of glucose metabolism or FHD.

PMID- 14686958
TI  - Effect of hormone replacement therapy on cardiovascular risk factors in
      postmenopausal women with diabetes.
AB  - BACKGROUND: Hormone replacement therapy (HRT) in postmenopausal women improves
      menopausal symptoms, decreases the incidence of osteoporotic fracture, but the
      effects on cardiovascular risk factors remain controversial. AIM: To test the
      hypothesis that HRT may have beneficial effects on the cardiovascular risk
      profile in postmenopausal women with diabetes. METHODS: One hundred and fifty
      postmenopausal patients with type 1 (T1DM) and type 2 diabetes (T2DM) were
      randomized to receive HRT (Kliofem) or placebo for 12 months. We monitored the
      effects on cardiovascular risk factors, including lipid profile, glycaemic
      control, blood pressure and body weight. RESULTS: Mean low-density lipoprotein
      (LDL) cholesterol was associated with a nonsignificant decrease [-0.14 mmol/l
      (CI=-0.44, 0.17) (p=0.37)] in the Kliofem-treated group. Total cholesterol fell
      by 0.42 mmol/l (CI=-0.78, -0.05) (p=0.027). High-density lipoprotein (HDL)
      cholesterol was reduced by a mean of 0.07 mmol/l compared to a mean rise of 0.12
      mmol/l on placebo. There were apparent differences in the treatment effects
      between T1DM and T2DM. There was no change in triglycerides or apoprotein B and
      no effect on glycaemic control, blood pressure or menopausal symptom scores. In
      the Kliofem group, BMI fell by 0.66 kg/m2 compared to an increase of 0.14 kg/m2
      for placebo patients (p=0.046). CONCLUSIONS: Although the long-term effects of
      HRT in women with or without diabetes appear to suggest that some types of HRT
      either confer no cardiovascular protection or may increase risk, the impact of
      Kliofem diabetic women on cardiovascular risk factors is probably neutral.

PMID- 14686959
TI  - Obesity in the Caribbean: the Jamaican experience.
AB  - AIM: This study was designed to investigate the point prevalence and pattern of
      obesity in the Jamaican adult population. METHODS: A two-stage-stratified random
      sampling design was used, and individuals aged 15 years and over were
      interviewed. In addition, anthropometric measurements were performed. The data
      were analysed using the SPSS statistical software version 8. Non-response was
      documented and factored into the final analysis of the survey data. RESULTS: A
      total of 2105 individuals responded to the all island survey, with 69% being
      females. Truncal obesity and gynoid obesity showed similar prevalence data. Both
      were affected by increasing age, being female, level of education attained and
      smoking status. CONCLUSIONS: Jamaica has a point prevalence of obesity, truncal
      36.2% and gynoid 34.1%, in the 15 and over age group.

PMID- 14686960
TI  - Comparison of the effects of glimepiride and glibenclamide on adipose tissue
      tumour necrosis factor-alpha mRNA expression and cellularity.
AB  - AIM: The aim of this study was to compare the effects of glimepiride and
      glibenclamide on tumour necrosis factor (TNF)-alpha expression and adipocyte
      cellularity in spontaneously diabetic, obese rats. METHODS: Eight-week-old male
      Otsuka Long-Evans Tokushima Fatty (OLETF) rats were randomized to receive
      glimepiride, glibenclamide or control treatment for 12 weeks, after which TNF
      alpha mRNA levels, adipose tissue cellularity and physiological parameters were
      measured. RESULTS: TNF-alpha mRNA expression in retroperitoneal fat tissue was
      significantly greater in the glibenclamide group (2.2 +/- 1.1), compared with the
      control group (0.9 +/- 0.4; p<0.05) or the glimepiride group (0.9 +/- 0.2;
      p<0.01). The mean fat-cell area in retroperitoneal fat tissue was increased at
      study endpoint in the glibenclamide group (13,764 +/- 7036 microm2), compared
      with both the control and glimepiride groups (10,755 +/- 6193 microm2 and 11,317
      +/- 5646 microm2 respectively; p<0.05). Investigation of cellularity revealed a
      decrease in the frequency of small fat cells and an increase in the frequency of
      large fat cells in both the glibenclamide and glimepiride groups compared with
      the control group, with a greater increase in large fat cells in the
      glibenclamide group. At study endpoint, insulin and triglyceride values were
      significantly higher in the active treatment groups compared with the control
      group; however, insulin levels were significantly greater in glibenclamide
      treated animals compared with glimepiride-treated animals. An oral glucose
      tolerance test performed at the end of the study showed that there were no
      significant differences among the three groups in terms of plasma glucose and
      insulin concentrations. CONCLUSIONS: This study suggests that although both
      glibenclamide and glimepiride may have a hypertrophisizing effect on fat cells in
      adipose tissues, this effect is greater with glibenclamide, leading to
      augmentation of TNF-alpha mRNA expression and possible exacerbation of insulin
      resistance.

PMID- 14686961
TI  - Role of fat amount and type in ameliorating diet-induced obesity: insights at the
      level of hypothalamic arcuate nucleus leptin receptor, neuropeptide Y and pro
      opiomelanocortin mRNA expression.
AB  - AIMS: Dietary fatty acid profile, independent of caloric percent of fat, is a
      major regulator of body adiposity. This study examined the effects of dietary fat
      amount and types on fat storage and hypothalamic gene expression in the mouse
      model of chronic diet-induced obesity. METHODS: The dietary interventions were in
      twofold: (1) the obesity was induced by a 13-week obesogenic fat diet compared
      with a low-fat (LF) diet, and (2) the reversibility was tested by using high n-3
      polyunsaturated fat (PUFA) and LF diets. Fifty-four C57Bl/6 mice were fed a high
      fat (59% in kcal) diet for 13 weeks and then classified as diet-induced obese
      (DIO) or diet-resistant (DR) mice according to upper and lower tertiles of body
      weight gain. The DIO mice were then subdivided into three groups for a 6-week
      secondary dietary intervention. Two of the groups were switched to either a high
      n-3 PUFA (DIO-n3) or a low-fat (10% in kcal, DIO-LF) diet, whereas the third
      (controls) and DR mice continued on the initial high-fat diet. Food efficiency
      was calculated as weekly body weight gain per gram of food intake. RESULTS: After
      switching the DIO mice to the n-3 PUFA or LF diet, their body weights were
      reduced to the level of the DR and LF mice. The food efficiencies were, from the
      highest to lowest, in the order: DIO>LF>DR>DIO-LF>DIO-n3. Using quantitative in
      situ hybridization, we found that the DIO mice had higher levels of leptin
      receptor (LR, +290%, p<0.005) and neuropeptide Y (NPY, +25%, p<0.05) mRNA
      expression in the hypothalamic arcuate nucleus (Arc) than the DR mice, whereas
      the level of pro-opiomelanocortin (POMC) mRNA expression was significantly
      reduced (-45%, p<0.01). All effects that were essentially returned to DR levels
      by the change to the n-3 PUFA diet and, with the exception of a failure to
      normalize Arc NPY mRNA levels, by the change to LF diet. CONCLUSIONS: Taken
      together, the present results show that both change in level and quality of
      dietary fat can potently alter hypothalamic neuropeptide expression and result in
      effective amelioration of diet-induced obesity. Interestingly, the n-3 PUFA diet
      when fed to already obese mice produced a pattern of hypothalamic gene expression
      similar to that in obesity resistant (DR) mice. It remains to be determined if
      the effects of n-3 fatty acids on brain neuropeptide gene expression are direct
      or indirect.

PMID- 14686962
TI  - The effect of polymorphism in the intestinal fatty acid-binding protein 2 gene on
      fat metabolism is associated with gender and obesity amongst non-diabetic
      Japanese-Americans.
AB  - AIM: The role of the codon 54 polymorphism of the fatty acid-binding protein 2
      (FABP2) gene on fat metabolism has been controversial. Assuming that the effects
      of the polymorphism were modulated by gender and obesity which were related to
      lipid and glucose metabolism, we investigated this polymorphism and its effect on
      fat metabolism according to such factors. METHODS: Subjects were Japanese
      Americans (123 men and 126 women) who were diagnosed as non-diabetic by a 75 g
      oral glucose tolerance test at the baseline. RESULTS: During approximately 7.8
      years, 49 (24 men and 25 women) were diagnosed with type 2 diabetes. In a Cox
      proportional hazards model, this polymorphism was not a significant variable in
      the incidence of diabetes in either gender. Amongst non-obese men with the Thr54
      allele, there was a significant elevation of triglycerides (TGs) (p=0.033)
      compared with alanine (Ala) homozygotes. Women with the Thr54 allele had
      significantly elevated total cholesterol (p=0.033) and low-density lipoprotein
      cholesterol (LDL-C) (p=0.023) compared with Ala54 homozygotes. CONCLUSIONS: These
      results therefore suggested that the effects of the FABP2 polymorphism on TG, LDL
      C and body mass index were associated with gender difference and obesity amongst
      non-diabetic Japanese-American subjects.

PMID- 14686963
TI  - Effects of the sibutramine therapy on pulmonary artery pressure in obese
      patients.
AB  - AIM: Obesity is a major global public health problem. Previous drugs
      (dexfenfluramine and fenfluramine) used for the treatment of obesity have been
      withdrawn due to various cardiac side effects. Sibutramine is an anti-obesity
      agent. The purpose of this study was to assess cardiac valve disease and
      pulmonary artery pressure (PAP) of the patients who used once daily doses of
      sibutramine. METHODS: One hundred and six obese patients (51 men and 55 women)
      determined to have minimal tricuspid regurgitation (TR) on echocardiographic
      examination were included in the study. All patients had a complete physical
      examination, complete blood count and measurement of lipid parameters, and
      echocardiography was performed by which cardiac valves and PAP were evaluated.
      After the mean duration of 24-week of follow up, all examinations were repeated
      for each patient. RESULTS: The drug was well tolerated by all patients for the
      follow-up period. A significant weight loss was recorded in all patients compared
      to the baseline values (93.1 +/- 9.6 kg vs. 85.8 +/- 7.7 kg, p<0.001). Blood
      pressures and heart rate of the patients increased compared to the baseline
      measurements (systolic 122.3 +/- 8.5 vs. 124 +/- 10.2 mmHg, p=0.128, diastolic
      79.3 +/- 4.7 vs. 80 +/- 5.7 mmHg, p=0.42 and heart rate 79.5 +/- 6.5 vs. 85 +/-
      5.7 beats/min, p<0.001). Echocardiographically determined aortic or mitral valve
      dysfunction appeared in none of the patients. PAP lightly increased after the
      treatment but the difference between pre and post-treatment values was not found
      statistically significant (14.7 +/- 1.8 vs. 16.3 +/- 1.6 mmHg, p=0.06).
      CONCLUSIONS: A 24-week treatment with sibutramine does not affect heart valves
      and pulmonary artery pressure.

PMID- 14686964
TI  - Effect of the angiotensin II receptor blocker candesartan on fibrinolysis in
      patients with mild hypertension.
AB  - AIM: Impaired fibrinolysis is frequently observed in patients with the metabolic
      syndrome. Aim of the study was to examine the short-term effect of angiotensin II
      receptor blockade on the fibrinolytic system. METHODS: Seventy-four patients with
      mild hypertension were randomly assigned to a 7-day treatment period with either
      16 mg candesartan cilexetil or placebo. Several variables of the fibrinolytic
      system such as plasminogen activator inhibitor-1 (PAI-1) antigen and activity,
      tissue plasminogen activator (t-PA) antigen and activity as well as circulating t
      PA/PAI-1 complexes were determined. RESULTS: At baseline, the body mass index but
      not blood pressure was positively associated with PAI-1 antigen (r=0.314, p<0.01)
      and PAI-1 activity (r=0.425, p<0.01) but negatively with t-PA activity (r=-0.187,
      p < 0.05). A 7-day treatment with 16 mg candesartan cilexetil resulted in a
      significant greater reduction of diastolic blood pressure (-10.3 +/- 10.8 mmHg
      vs.-5.8 +/- 8.5 mmHg, p=0.03). However, there was no significant effect of
      candesartan on all parameters of the fibrinolytic system under investigation,
      i.e. circulating PAI-1 antigen, PAI-1 activity, t-PA antigen, t-PA activity and t
      PA/PAI-1 complexes. Furthermore, candesartan did not affect the characteristic
      circadian pattern of the variables of the fibrinolytic system. CONCLUSION: We
      conclude that short-term blockade of the angiotensin II receptor subtype 1 with
      candesartan does not have an impact on fibrinolysis in patients with mild
      hypertension.

PMID- 14686965
TI  - The effect of acarbose on insulin resistance in obese hypertensive subjects with
      normal glucose tolerance: a randomized controlled study.
AB  - AIM: Acarbose, a glucose oxidase inhibitor, delays the absorption of glucose thus
      reducing post-prandial blood glucose level, haemoglobin A1c (HbA1c) and insulin
      resistance in patients with diabetes mellitus and in subjects with impaired
      glucose tolerance. The effect of acarbose in subjects with normal glucose
      tolerance (NGT) has hitherto not been examined. The aim of the present study was
      to examine the effect of acarbose in obese hypertensive subjects with NGT.
      METHODS: A double-blinded, parallel group study was performed on 56 male subjects
      with hypertension, body mass index (BMI) 27-35 kg/m2, fasting blood glucose < or
      =6 mmol/l and a normal oral glucose tolerance test. Blood pressure, HbA1c, lipid
      profile and insulin resistance [homeostasis model assessment (HOMA) index] were
      determined initially and following 24 weeks of acarbose, 150 mg/day or placebo.
      The primary end point was the change in insulin resistance. Anti-hypertensive
      treatment and diet were kept constant during the study. RESULTS: Insulin
      resistance decreased in acarbose users but not on placebo. HOMA index declined
      from 5.36 +/- 1.7 to 4.10 +/- 1.6 (p=0.001) on acarbose, the corresponding values
      on placebo were 5.44 +/- 1.9 and 5.53 +/- 1.7. A decrease in serum triglyceride
      values (2.16 +/- 0.16 mmol/l to 1.76 +/- 0.15 mmol/l, p=0.02) took place on
      acarbose with no change on placebo. There was no change in BMI, low-density
      lipoprotein or high-density lipoprotein values in either group. Blood pressure
      declined equally in both the groups, probably due to better patient compliance.
      CONCLUSIONS: Acarbose may reduce insulin resistance and triglycerides also in
      obese hypertensive subjects with normal glucose tolerance.

PMID- 14686966
TI  - Lack of concordance between plasma markers of cardiovascular risk and intima
      media thickness in patients with type 2 diabetes.
AB  - AIM: Endothelial dysfunction, oxidative stress and systemic inflammation play an
      important role in the enhanced cardiovascular risk in diabetes. Carotid intima
      media thickness (IMT), a widely accepted marker of subclinical atherosclerosis,
      is known to be increased in patients with type 2 diabetes. The relationships
      between plasma markers of cardiac risk and carotid IMT are not well known. We
      therefore studied a group of patients with type 2 diabetes to evaluate the
      relationships between plasma markers of cardiac risk and carotid IMT. DESIGN AND
      PATIENTS: We measured carotid IMT and the levels of soluble endothelial adhesion
      molecules [sE-selectin, intercellular cell adhesion molecule-1 (sICAM-1) and
      vascular cell adhesion molecule-1 (sVCAM-1)], C-reactive protein (CRP) and 8
      isoprostane in 40 patients with type 2 diabetes without clinical macrovascular
      complications (HbA1c<10%, duration of diabetes<12 years) and 25 healthy subjects.
      We then examined the correlations between these plasma markers, carotid IMT and
      various clinical and biochemical parameters. RESULTS: Diabetic patients had
      higher plasma sE-selectin (p=0.03), sICAM-1 (p=0.05), CRP (p=0.047) and 8
      isoprostane (p=0.001) concentrations than control subjects. Mean IMT values were
      identical (0.63 +/- 0.02 mm) in diabetic (range, 0.40-0.92 mm) and healthy
      subjects (range, 0.45-0.85 mm). In diabetic patients, stepwise multivariate
      analysis showed that HbA1c and plasma glucose were independent predictors of sE
      selectin (r2=0.19 and r2=0.17, p<0.01, respectively), whereas waist circumference
      and body mass index (BMI) were predictors of sICAM-1 (r2=0.27, p=0.001 and
      r2=0.22, p=0.002, respectively). Waist circumference was the only predictor of
      CRP (r2=0.2, p<0.01), and systolic blood pressure was the only predictor of 8
      isoprostane (r2=0.19, p=0.006). In control subjects, similar analysis showed that
      plasma glucose and waist circumference were predictors of sE-selectin and sICAM
      1, respectively (r2=0.2, p<0.05). CONCLUSIONS: These results indicate that some
      well-controlled type 2 diabetic patients free of clinical macrovascular
      complications have elevated plasma markers of cardiovascular risk without having
      increased IMT. The elevation of plasma markers of endothelial cell activation (sE
      selectin and s-ICAM-1) or inflammation (CRP) and oxidative stress (8-isoprostane)
      in diabetics vs. controls is distinct from and cannot be explained simply by
      differences in the burden of atherosclerosis as assessed by carotid IMT.

PMID- 14686967
TI  - Insulin resistance and coronary artery disease: body mass index may have affected
      results.

PMID- 14686968
TI  - Diagnosis, staging, and monitoring of cutaneous T-cell lymphoma.
AB  - Cutaneous T-cell lymphoma includes mycosis fungoides and its leukemic variant,
      the Sezary syndrome. This review discusses the clinical, histopathologic,
      immunophenotypic and immunogenotypic features of cutaneous T-cell lymphoma as
      they apply to the diagnosis, staging and monitoring of this disease.

PMID- 14686970
TI  - Treatment of patch-stage mycosis fungoides with topical corticosteroids.
AB  - Experience at the University of California, San Francisco (UCSF), in the
      management of patch-stage mycosis fungoides (MF) with topical, predominantly high
      potency, corticosteroids is reviewed. The technique of applications is discussed
      in detail. Approximately 200 patients have been treated. The results are very
      favorable. The response rate is over 90%. Side-effects are minor. Topical
      clobetasol is the first-line treatment for early stage MF at UCSF.

PMID- 14686969
TI  - Treatment planning in cutaneous T-cell lymphoma.
AB  - Effective long-term management of cutaneous T-cell lymphoma (CTCL) requires
      administration of skin-directed therapies such as topically applied nitrogen
      mustard or photochemotherapy to achieve a complete response in clinically early
      disease (patch and thin-plaque-phase mycosis fungoides, MF) and often the
      concomitant administration of well-tolerated drugs with systemic effects such as
      interferon alfa, bexarotene, methotrexate or extracorporeal photopheresis in more
      advanced, but not highly aggressive/nontransformed disease (thick plaque or tumor
      phase MF or erythrodermic CTCL). The author's approach is provided as a guide for
      dermatologists in private practice.

PMID- 14686971
TI  - Management with topical nitrogen mustard in mycosis fungoides.
AB  - Topical nitrogen mustard (mechlorethamine, NM) has been used as primary therapy
      for management of patients with mycosis fungoides (MF) since the 1950s. Many
      investigators have demonstrated the efficacy of topical NM in patch and/or plaque
      disease of MF. Updated results from Stanford also confirm the clinical efficacy.
      The complete response (CR) rates reported are 76-80% for patients with limited
      patch/plaque (stage IA), and 35-68% for those with generalized patch/plaque
      (stage IB) disease. Topical NM can be used as an aqueous (water) or ointment
      based preparation. The efficacy results are similar in patients who were treated
      with aqueous versus ointment preparations. Maintenance regimens used are
      variable, but there is no data to suggest that a longer maintenance duration
      results in greater potential for long-term remission. Most patients who achieve
      initial CR with topical NM tend to require NM-only for disease management.
      Topical NM is equally effective when used as salvage therapy with disease
      relapse. The most common toxicity of topical NM therapy is contact irritant or
      allergic reaction. The potential for allergic reaction is significantly reduced
      (< 10%) when NM is used as an ointment preparation. The potential for secondary
      skin cancer development is increased in patients who have used multiple
      sequential topical skin-damaging therapies or NM in the genital skin, but not in
      patients who have used NM as monotherapy (avoiding genital skin application).
      Topical NM is used safely in pediatric patients and there is no evidence of any
      clinically significant systemic absorption of topically applied NM.

PMID- 14686972
TI  - Topical carmustine (BCNU) in the treatment of mycosis fungoides.
AB  - The University of California, San Francisco (UCSF), experience with topical
      carmustine (BCNU) in the treatment of approximately 200 patients with mycosis
      fungoides (MF) is summarized. Topical BCNU is an effective treatment for patch-
      and early plaque-stage MF. Side-effects are usually not a major deterrent to
      continuation of therapy.

PMID- 14686973
TI  - Phototherapy for cutaneous T-cell lymphoma.
AB  - Phototherapy has been utilized for decades in the treatment of various
      dermatologic conditions, including cutaneous T-cell lymphoma (CTCL). Currently, a
      number of light sources are available, and selection of the specific modality is
      based on a number of factors, the most important of which is disease stage. The
      efficacy of broadband ultraviolet B (UVB) is limited to the patch stage, while
      psoralen and ultraviolet A (PUVA) is capable of clearing plaques and, sometimes,
      early tumors. Narrowband UVB is also effective for early stages and has practical
      advantages over PUVA, but more studies are needed to more fully evaluate its role
      in CTCL. Long-wave ultraviolet A (UVA1) has likewise shown efficacy, supported by
      findings of apoptosis induction in UVA1-treated cells. Long-term remissions have
      been reported for PUVA, but in the majority of cases, maintenance therapy was
      necessary. Although beneficial as monotherapy for early stages of the disease,
      phototherapy is also a useful adjunct to other modalities such as interferons,
      retinoids and electron beam therapy. Studies are ongoing to refine protocols for
      combination therapy, with the goal of improving efficacy, while minimizing
      adverse effects.

PMID- 14686974
TI  - Interferon in the treatment of cutaneous T-cell lymphoma.
AB  - Interferons are polypeptides with a broad range of in vivo effects that have
      shown efficacy in cutaneous T-cell lymphoma (CTCL). Particularly useful is alfa
      interferon (IFN) which, as a single agent, has shown partial remission rates of >
      50% and complete responses of > 20%. Side-effects are predictable, generally well
      tolerated and dose-related. The efficacy of IFN has increased with combination
      therapy without any significant increase in attendant side-effects. An update on
      the specifics of the different IFN subtypes, their inherent biologic activity,
      pharmacokinetics, efficacy and safety in CTCL is presented in this paper.

PMID- 14686975
TI  - Retinoids: therapeutic applications and mechanisms of action in cutaneous T-cell
      lymphoma.
AB  - Retinoids, natural and synthetic derivatives of vitamin A, are biological
      regulators of differentiation, proliferation, apoptosis, and immune response.
      Retinoic-acid-receptor-selective retinoids (all-trans retinoic acid, 13-cis
      retinoic acid, and the synthetic analogs isotretinoin, etretinate and acitretin)
      have been used for years as monotherapy and/or in combination for treatment of
      cutaneous T-cell lymphoma (CTCL). Orally administered bexarotene, the first
      synthetic highly selective retinoid-X-receptor retinoid to be approved by the FDA
      for CTCL, was shown to be active against the cutaneous manifestations of all
      stages of CTCL. The topical gel formulation was also effective for early
      cutaneous manifestations of CTCL or as an adjunct to systemic or phototherapy.
      Bexarotene treatment induces apoptosis of CTCL cells with down-regulation of its
      receptors and of survivin, an inhibitor of apoptosis. Identification of new
      receptor subtype-selective retinoids, combination of various receptor-selective
      retinoids or other agents, and a new drug delivery system may improve the
      clinical efficacy of retinoids in the future.

PMID- 14686976
TI  - The use of cytokines, fusion proteins and antibodies to treat cutaneous T-cell
      lymphoma.
AB  - It has long been known that certain immune augmenting therapeutics, particularly
      interferon alpha, can exert profound salutary effects on the clinical progress of
      patients with cutaneous T-cell lymphoma. Emerging evidence that the host immune
      response may play an important role in the control of this disorder has led to
      the clinical application of other cytokines including interleukin-12 and
      interferon gamma. In this review, the authors will summarize current knowledge
      regarding the use of cytokines, fusion proteins and antibodies for the treatment
      of cutaneous T-cell lymphoma.

PMID- 14686977
TI  - The treatment of cutaneous T-cell lymphoma with photopheresis.
AB  - Photopheresis or extracorporeal photochemotherapy (ECP) is an immunomodulating
      procedure that has been available for the treatment of cutaneous T-cell lymphoma
      (CTCL) since 1987. A concentrated white blood cell (WBC) sample spiked with 8
      methoxypsoralen (methoxsalen) is exposed to an ultraviolet A light source, then
      all blood components are returned to the patient. Treatment of mycosis fungoides
      (MF) and Sezary syndrome (SS) with ECP has been reported in over 400 patients.
      The combined overall response rate for all stages of CTCL is 55.7% (244 out of
      438) with 17.6% (77 out of 438) achieving a complete response. Efficacy in
      treating certain clinical stages (IB, IIA, III and IVA) and skin stages (T2 and
      T4) of MF and SS is favorable, although randomized trials comparing ECP to other
      standard therapies are needed. The use of ECP to treat early stage patients
      remains controversial. Efforts to establish the effectiveness of combining ECP
      with other newer immunoadjuvant therapies and modifications of the procedure to
      enhance immunomodulation are exciting prospects for patients with CTCL.

PMID- 14686978
TI  - Mycosis fungoides: radiation therapy.
AB  - Radiation therapy is the most effective single agent for the treatment of mycosis
      fungoides. There are well-defined dose-response relationships for achieving a
      complete response as well as the durability of this response. Techniques of
      electron beam therapy have been developed that permit treatment of the entire
      skin. Total-skin electron beam therapy is an important form of management,
      especially for patients who have thick generalized plaque or tumorous disease.
      Radiation therapy may also be used selectively for treatment of extracutaneous
      disease.

PMID- 14686979
TI  - Systemic chemotherapy for the treatment of mycosis fungoides and Sezary syndrome.
AB  - The treatment of mycosis fungoides and Sezary syndrome is unique. The treatments
      of choice are highly stage-and practitioner-dependent. For early stage patients,
      treatment with palliative topical therapies is often adequate to yield excellent,
      high-quality and durable responses. For the more advanced stages, systemic
      approaches are more appropriate, either alone or in combination, to palliate
      patients. There is still little convincing evidence from randomized trials that
      any single approach is favorable for improving survival. Many practitioners
      believe the disease can be controlled with the host immune system, but there
      again is little scientific support for this conclusion. It has been hypothesized
      that some of our therapies work through this mechanism, such as photopheresis and
      perhaps even psoralen and ultraviolet A. Unfortunately, even the use of biologic
      response modifiers, such as interferon and the interleukins, is not absolutely
      supportive of an active role for immune surveillance since these agents have been
      shown to have cytotoxic and differentiating effects. Because of the above, many
      practitioners have actively discouraged the use of chemotherapy because it may
      impair the host immune system; certainly, the purine analogs would fall into this
      category. However, there is little evidence supporting significant immune effects
      for other chemotherapeutics, and clearly, the responses seen would support their
      use in appropriate patients. As the present authors will detail in this paper,
      the advances in understanding cancer biology and mechanisms of resistance should,
      in the future, lead to optimal selection of agents that are predicted to be
      optimally active, limiting the toxicity and waste associated with ineffective
      drug usage.

PMID- 14686981
TI  - Systemic antibiotic treatment in upper and lower respiratory tract infections:
      official French guidelines.

PMID- 14686982
TI  - Epidemiology of methicillin-resistant staphylococci in Europe.
AB  - Methicillin-resistant staphylococci are mostly resistant not only to all beta
      lactams but also to a wide range of other antibiotics, and have emerged as major
      nosocomial pathogens during the past two decades. Considerable variations in the
      prevalence of methicillin-resistant Staphylococcus aureus (MRSA) exist between
      institutions and between geographic areas. In Europe, in general, a north-south
      gradient is observed, MRSA strains being rare in Scandinavian hospitals (<2%) and
      far more prevalent in Mediterranean hospitals (>40%). Whether low or high, the
      rates of MRSA prevalence in European countries have remained approximately the
      same during the last decade. Recent findings suggest that MRSA might also be
      emerging as a community-acquired pathogen. The first stage in the emergence of
      MRSA is its acquisition by methicillin-susceptible S. aureus, and the integration
      into its chromosome, of the mecA gene, which, together with the other mec genes,
      is carried on a mobile genetic element, the staphylococcal chromosomal cassette
      mec (SCCmec). The origin of SCCmec elements as well as the mechanisms of their
      acquisition remain unknown. Molecular epidemiology studies using different
      techniques clearly indicate that the massive geographic spread of MRSA results
      from the dissemination of relatively few highly epidemic clones. Five major
      lineages (the so-called Iberian, Brazilian, Hungarian, New York/Japan and
      pediatric pandemic MRSA clones) have been defined. In Europe, the Iberian clone
      has been reported in several countries; the Brazilian, pediatric and Hungarian
      clones have also been detected, but less frequently. A unique Italian clone is
      predominant in Italy. As with S. aureus, coagulase-negative staphylococci (CNS)
      represent a serious concern in hospital-acquired infections. Despite marked
      geographic variations, in some areas of Europe high proportions (60-70%) of CNS
      are methicillin resistant. The formation of biofilm is a key virulence factor of
      S. epidermidis, the prominent CNS pathogen, which is the most common cause of
      bacteremia in device-related infections. Another emerging nosocomial pathogen, S.
      hemolyticus, is characterized by a tendency to develop multiple antibiotic
      resistances, with a unique predisposition to glycopeptide resistance.

PMID- 14686983
TI  - Cytomegalovirus-associated acute transverse myelitis in immunocompetent adults.
AB  - We report a case of transverse myelitis as a complication of acute
      cytomegalovirus (CMV) infection in immunocompetent patients; and review the
      literature on the entity. Primary CMV infection was documented by CMV antigenemia
      and high serum titers of CMV IgM and IgG antibodies. Cerebrospinal fluid (CSF)
      pleocytosis indicated central nervous system inflammation; CSF polymerase chain
      reaction (PCR) for CMV, however, was negative. The results of magnetic resonance
      imaging of the myelon were normal. Although CMV-associated transverse myelitis
      has been well described in HIV-positive individuals, but is very rare in
      immunocompetent individuals. It remains unclear whether the neuronal damage is
      immune mediated or due to a cytotoxic effect of viral infection. The outcome is
      mainly favorable.

PMID- 14686984
TI  - PCR-RFLP detection and species identification of fungal pathogens in patients
      with febrile neutropenia.
AB  - OBJECTIVE: To assess the usefulness of polymerase chain reaction (PCR) assays in
      the diagnosis of fungal infections in immunocompromised patients. METHODS: A
      rapid and sensitive PCR-based assay for the detection and identification of
      fungal pathogens was designed and applicability of this method was investigated
      in a group of children with cancer and febrile neutropenia (FN). RESULTS: The
      ITS2 sequences and adjacent regions of 40 fungal pathogens were analyzed and
      primers for detection of all analyzed fungal species were designed. Amplification
      product length polymorphism (APLP) and restriction fragment length polymorphism
      (RFLP) generated genus- or species-specific patterns. The sensitivity of the
      method was approximately three cells of Candida albicans per 1 mL of blood. The
      results were available within 8 h after sample collection. The method was tested
      on 53 blood samples and one lung biopsy sample from 24 children with cancer and
      febrile neutropenia (FN). The PCR assay detected fungal DNA in 25 clinical
      samples from ten patients. Blood cultures were positive in only five samples,
      while another two blood-culture negative patients had positive cultures from
      throat swabs. The remaining 14 patients were both culture- and PCR-negative.
      Culture-isolated strains matched completely those obtained by PCR-APLP-RFLP
      identification. The identity of fungal species was confirmed by direct sequencing
      of amplified products. CONCLUSION: Our results suggest that PCR-APLP-RFLP assays
      can be useful in the diagnosis of fungal infections in immunocompromised
      patients.

PMID- 14686985
TI  - Promoting resistance by the emission of antibiotics from hospitals and households
      into effluent.
AB  - OBJECTIVE: There is growing concern about bacterial resistance to antimicrobials.
      The majority of antibiotics used are only partially metabolized after
      administration, and are released via patient excreta into the municipal sewage
      system. Data on the use of antibiotics and their emission into hospital effluent
      are not available. METHODS: Antibiotic consumption in Germany was calculated on
      the basis of five hospitals of varying size and medical service spectrum and on
      prescriptions issued by medical practitioners. The predicted environmental
      concentration (PEC) was calculated for hospital effluent and for municipal
      sewage. The PECs were compared both with published minimum inhibitory
      concentrations (MIC50) for sensitive pathogenic bacteria and with the predicted
      no-effect concentrations (PNECs). RESULTS: The amount of antibiotics emitted into
      hospital effluent may reach and exceed the MIC50 of susceptible pathogenic
      bacteria. The PEC/PNEC ratio is highest for hospital effluent (in some cases 10
      20 times the MIC50) and frequently > 1 for municipal sewage. PECs are high enough
      for some compounds to have a PEC/PNEC ratio > 1 even in surface water.
      CONCLUSION: The volume of antibiotics used in hospitals and private households
      and released into effluent and municipal sewage indicates a selection pressure on
      bacteria. Steps should be taken to reduce the risk by proper handling of
      antibiotics and their residues both in hospitals and by private users.

PMID- 14686986
TI  - Esophageal perforation secondary to angio-invasive Candida glabrata following
      hemopoietic stem cell transplantation.
AB  - Esophageal perforation due to Candida glabrata is a rare entity. This organism is
      uncommonly recognized to be angio-invasive and cause gastrointestinal tract
      perforation. Herein, we describe a case of invasive C. glabrata infection leading
      to esophageal perforation in a patient undergoing hemopoietic stem cell
      transplantation.

PMID- 14686987
TI  - Curvularia--favorable response to oral itraconazole therapy in two patients with
      locally invasive phaeohyphomycosis.
AB  - Curvularia species are ubiquitous and occasionally lead to infections in humans.
      In immunosuppressed patients, infections are often serious, and systemic
      dissemination is not uncommon. The optimal antifungal therapy is unclear. I here
      present two cases, a healthy man with locally invasive, mulicentric paranasal
      fungal sinusitis, and a case of progressive verrucal distal onychomycosis that
      developed while the patient was undergoing accelerated chemotherapy for non
      Hodgkin's lymphoma. Both patients showed excellent responses to treatment with
      itraconazole suspension. Oral itraconazole may provide a safe and effective
      alternative for patients with locally invasive non-disseminated mycoses due to
      Curvularia species.

PMID- 14686988
TI  - Fulminant invasive pulmonary aspergillosis in immunocompetent patients--a two
      case report.
AB  - Two cases of invasive aspergillosis (IA) in immunocompetent patients with a
      fulminant fatal outcome are reported. Both patients were elderly and had a
      history of chronic lung disease treated with prolonged inhaled corticosteroids
      and a short course of systemic corticosteroids. They presented with dyspnea and
      fever, their respiratory function deteriorated rapidly, and they died 7 days
      after admission. Aspergillus fumigatus was cultured from respiratory samples. IA
      was confirmed in one case by necropsy that showed diffuse bilateral necrotizing
      pneumonitis and myocarditis. In the other case, IA diagnosis was established by
      thoracic CT scan plus detection of Aspergillus antigen in two blood samples.
      These two cases demonstrate that short-term corticosteroid therapy in
      immunocompetent patients with underlying chronic lung conditions is a risk factor
      for IA, and that its evolution can be fulminant.

PMID- 14686990
TI  - Liver abscess due to Bacillus cereus: a case report.
AB  - Bacillus cereus is a food-borne pathogen that causes a self-limiting
      gastroenteritis. We describe the case of a 72-year-old woman admitted to our
      hospital because of acute abdominal colic pain. Over a 2-day period, her clinical
      condition deteriorated rapidly, with the appearance of acute abdomen. Computed
      tomography investigation of the abdomen showed a liver abscess (diameter
      approximately 3 cm). At laparotomy, the abscess was found to be ruptured to the
      free peritoneal cavity. The final clinical diagnosis was acute peritonitis due to
      a ruptured liver abscess. Bacillus cereus was isolated from culture of the pus.
      Up to now, no case of liver abscess due to this organism has been reported.

PMID- 14686989
TI  - European-wide distribution of Pseudomonas aeruginosa clone C.
AB  - A collection of 77 epidemiologically unrelated Pseudomonas aeruginosa isolates
      was screened for the occurrence of clone C isolates by the appearance of
      characteristic SpeI fragment patterns obtained by pulsed-field gel
      electrophoresis. Three strains with a clone C characteristic SpeI fragment
      pattern were found which also harbored the clone C-specific plasmid either in the
      free form or chromosomally integrated. Genomic islands were detected in the new
      clone C strains, as in already characterized clone C strains. Clone C not only
      infected cystic fibrosis patients throughout Europe, but was also found in the UK
      as an isolate in urinary tract infections and in peritoneal dialysis fluid, in
      addition to an otitis media isolate. Therefore, P. aeruginosa clone C is widely
      distributed in Europe, with a broad pathogenic potential.

PMID- 14686991
TI  - Disseminated Aspergillus terreus infection arising from cutaneous inoculation
      treated with caspofungin.
AB  - A case of disseminated Aspergillus terreus infection in a patient with prolonged
      neutropenia after stem cell transplant for myeloma is reported. The isolate was
      resistant to amphotericin B in vitro, and the patient was successfully managed
      with surgical debridement and the recently licensed antifungal agent caspofungin.
      There are many challenges associated with treating invasive aspergillosis,
      particularly that due to A. terreus, and the early use of caspofungin should be
      considered.

PMID- 14686992
TI  - Bacteremia caused by a novel species of Sphingobacterium.
AB  - A Gram-negative rod was isolated from the blood cultures of an 84-year-old man
      with foot cellulitis. The bacterium was first identified as Sphingobacterium
      spiritivorum on the basis of standard assimilation tests. However, sequencing
      analysis of its 16S rRNA genes and whole genome hybridization studies with other
      related bacteria showed that this isolate belongs to a so far undescribed species
      of Sphingobacterium, close to S. mizutae. This bacterium was susceptible to most
      of the antibiotics tested, including glycopeptides, but was resistant to
      aminoglycosides and polymyxins. Treatment with amoxicillin-clavulanate cured the
      infection.

PMID- 14686994
TI  - Clinical microbiological case: Vomiting followed by breathlessness.

PMID- 14686993
TI  - Primary meningococcal conjunctivitis.
AB  - Neisseria meningitidis is an uncommon cause of acute bacterial conjunctivitis.
      One case of primary meningococcal conjunctivitis in a healthy 6-year-old boy is
      reported. The patient was initially treated with a topical instillation of
      polymyxin B, neomycin and gramicidin in ophthalmic solution, and this was
      followed by systemic rifampin once the diagnosis had been established. No ocular
      or systemic complications developed.

PMID- 14686995
TI  - Clinical microbiological case: Itchy furunculosis on return from South Africa.

PMID- 14686996
TI  - In vitro activity of ravuconazole against Zygomycetes, Scedosporium and Fusarium
      isolates.

PMID- 14686997
TI  - Catalase-negative Staphylococcus aureus: a rare cause of catheter-related
      bacteremia.

PMID- 14686998
TI  - 100th anniversary of a great victory over typhus.

PMID- 14686999
TI  - Antimicrobial resistance patterns of respiratory pathogens: a local report from
      Turkey.

PMID- 14687000
TI  - Relapsing brucellosis in a patient infected with the human immunodeficiency virus
      (HIV).

PMID- 14687001
TI  - A rare cause of pericarditis.

PMID- 14687006
TI  - Effects of acute or chronic administration of anti-migraine drugs sumatriptan and
      zolmitriptan on serotonin synthesis in the rat brain.
AB  - Triptans are 5-HT1 receptor agonists used as anti-migraine drugs. They act
      primarily on meningeal blood vessels and on trigeminovascular afferents, but they
      may also exert central effects. We studied the regional effects of acute and
      chronic treatment with sumatriptan or zolmitriptan on the rate of serotonin (5
      HT) synthesis in the rat brain, using the alpha-14C-methyl-L-tryptophan
      quantitative autoradiographic method. Sumatriptan at low (300 microg/kg, s.c.)
      and high (1 mg/kg) doses, as well as zolmitriptan (100 microg/kg), acutely
      decreased (15-40%, P < 0.05-0.001) 5-HT synthetic rate in many brain regions,
      including the dorsal raphe nucleus. Chronically, sumatriptan (21 days,
      approximately 300 microg/kg per day via osmotic minipumps) induced significant
      increases in the 5-HT synthesis rate in many projection areas but had no effect
      in the dorsal raphe nucleus. The acute effects on 5-HT synthesis rate would be
      compatible with activation of 5-HT1 autoreceptors that inhibit serotonin release.
      In contrast, the increased 5-HT synthesis rate observed after chronic sumatriptan
      might possibly result from a down-regulation/desensitization of 5-HT1 receptors
      and/or unmasking of excitatory triptan-sensitive 5-HT receptors. Overall, the
      present findings indicate that not only zolmitriptan but also sumatriptan affect
      brain serotonergic neurotransmission.

PMID- 14687007
TI  - Clinical features of migraine: a cross-sectional study in patients aged three to
      sixty-nine.
AB  - We investigated 260 consecutive patients classified as migraine cases aged 3-69
      at two tertiary headache centres, one for children and adolescents and the other
      for adults to evaluate the relationship between age and clinical features of
      migraine cross-sectionally. We only included subjects with definite migraine
      without or with aura and we excluded subjects with coexisting tension-type
      headache, medication overuse and/or other clinically relevant disorders. The
      percentage of males decreased markedly from childhood to adulthood and this
      affected the evaluation of age-related changes in male patients, as only large
      differences reached the level of statistical significance. In females, the
      headache duration and the prevalence of unilateral, pulsating pain, photophobia
      and phonophobia increased, whereas the prevalence of aggravation by physical
      activity decreased with age. In conclusion, this cross-sectional, clinic-based
      study on a strictly defined sample of 260 consecutive patients with definite
      migraine covering a wide range of age from the very young to the old suggests
      marked age-related differences of the clinical features of migraine in females
      and failed to demonstrate similar differences in males due to the small number of
      adult male migraineurs.

PMID- 14687008
TI  - Prognosis of migraine with aura.
AB  - The present study is a 16-year follow-up study assessing the long-term outcome of
      migraine with aura (MA). Additionally possible predictive factors in the
      prognosis of MA were evaluated. Patients were recruited from the files of Danish
      headache clinics. A total of 53 patients (11M:42F) with MA (IHS criteria)
      participated in a follow-up interview. At follow-up attacks had ceased (no MA for
      2 years) in 36% of patients. Attacks had ceased in 55% of males and 31% of
      females (P = 0.17). Attacks had ceased in 41% of patients with visual aura
      without other aura symptoms and in 25% of those with sensory or aphasic aura
      besides their visual aura (P = 0.36). Among those with attacks of MA at follow-up
      frequency of attacks and headache intensity was improved in 44% and 41% of the
      patients, respectively. The results point to a favourable evolution of MA and
      suggest possible predictive factors.

PMID- 14687009
TI  - Characteristics of postictal headache in patients with partial epilepsy.
AB  - Migraine-like features sometimes characterize the headache that follows epileptic
      seizure (postictal headache, PIH). We compared patients with different types of
      epilepsy to investigate the association between migraine-like PIH and seizure
      type. Subjects comprised 364 patients with partial epilepsy. Epilepsy types were
      temporal lobe epilepsy (TLE, n = 177), frontal lobe epilepsy (FLE, n = 116), and
      occipital lobe epilepsy (OLE, n = 71). Patients participated in a structured
      interview pertaining to PIH as well as interictal headache and family history of
      migraine. Headaches were classified according to the International Headache
      Society criteria, which was modified for this study. Forty percent had PIH and
      26% of these patients had migraine-like PIH. Migraine-like PIH occurred
      significantly more often in cases of TLE and OLE than in cases of FLE. In
      addition, the incidence of interictal migraine headache was significantly higher
      in patients with migraine-like PIH. These results suggest that migraine-like PIH
      is related to particular regions of epileptogenic focus and that susceptibility
      to migraine headache predisposes to migraine-like PIH.

PMID- 14687010
TI  - Physiotherapy for tension-type headache: a controlled study.
AB  - The role of non-pharmacological therapies in the preventive treatment of tension
      type headache (TTH) is still an object of debate. The primary aim of this study
      was therefore to investigate the therapeutic effect of physiotherapy in properly
      classified patients with TTH in a controlled trial. Fifty patients with TTH, 26
      with episodic, frequent (ETTH) and 24 with chronic TTH (CTTH) fulfilling the
      International Headache Society classification criteria were included in the
      study. After a 4-week run-in period, they were randomized to either an 8-week
      period of standardized physiotherapy (group 1) or to an 8-week observation period
      followed by an identical course of physiotherapy (group 2); after the
      physiotherapy all patients were followed for a 12-week follow-up period. We then
      evaluated the number of days with headache, severity and duration of the headache
      attacks, and drug consumption for symptomatic treatment before and after the
      course of physiotherapy. Forty-eight patients completed the study. The average
      number of days with headache per 4-week period was reduced from 16.3 days at
      baseline to 12.3 days in the last 4 weeks of treatment [from 14.5 days to 10.5
      days (P < 0.001) in group 1 and from 18.1 days to 14.1 days (P < 0.001) in group
      2]. Severity and duration of headache as well as drug consumption were unchanged
      throughout the study. Analysing the response to treatment separately in the
      various subgroups, we found that the number of responders was significantly
      higher among patients with CTTH vs. patients with ETTH (P < 0.002) and in females
      vs. males (P < 0.02). No differences were found between patients with and without
      disorder of pericranial muscles. We conclude that a standardized physiotherapy
      programme has a good therapeutic effect, albeit on a restricted group of
      patients.

PMID- 14687011
TI  - Neutrophil-free radical generation and enzymatic antioxidants in migraine
      patients.
AB  - The present study was undertaken to elucidate the role of circulating neutrophils
      if any in oxidative stress in migraine by evaluating free radical generation and
      activities of enzymatic antioxidants in the blood in 55 patients with migraine
      and 60 healthy controls. Free radical generation was assessed by flow cytometry,
      while activity of catalase, superoxide dismutase (SOD) and glutathione peroxidase
      (GPx) was estimated in blood polymorphonuclear neutrophils (PMNs) by standard
      procedures. Platelet SOD was also measured. No significant change was found in
      free radical generation and in the activity of catalase, SOD and GPx in migraine
      patients. Univariate analysis of PMN catalase level revealed that migraineurs
      with a positive family history had significantly lower catalase activity compared
      with those with a negative family history. No correlation was found in the
      activity of antioxidant enzymes with age, duration of disease, time since last
      attack and headache index. The platelet SOD also did not show any significant
      change in patients of migraine without aura. Platelet aggregation in the presence
      or absence of PMNs was also not altered significantly. Thus the findings of the
      present study suggest that neutrophils are not the cause of oxidative stress
      observed in migraine patients.

PMID- 14687012
TI  - Suppression of pain and the R2 component of the blink reflex during optokinetic
      stimulation.
AB  - The effect of exposure to a rotating optokinetic drum on the electrically evoked
      blink reflex was investigated in 20 healthy volunteers. Pain ratings and the area
      under the curve of the R2 component of the blink reflex to innocuous and
      nociceptive trigeminal stimulation decreased substantially during and after
      optokinetic stimulation. At low shock intensities, R2 decreased most during
      optokinetic stimulation in subjects who did not develop symptoms of motion
      sickness. In contrast, during the recovery period after optokinetic stimulation,
      suppression of R2 to moderate and intense stimuli was greatest in the most
      nauseated subjects. These findings suggest that a mechanism that suppresses
      symptoms of motion sickness during sensory conflict also inhibits activity in
      wide dynamic range neurones in the trigeminal nucleus caudalis. Nausea in the
      absence of sensory conflict may inhibit R2 to intense electrical stimulation by
      provoking diffuse noxious inhibitory controls.

PMID- 14687013
TI  - Non-lateralized pain in a case of chronic paroxysmal hemicrania?
AB  - We describe a man with chronic paroxysmal hemicrania, who remained free of
      headaches on indomethacin, 25 mg once or twice daily. However, in this case, in
      contrast to typical cases of paroxysmal hemicrania, the pain of the headaches was
      nonlateralized and was located in the centre of the forehead. The headaches were
      not associated with local autonomic symptoms or signs involving the eyes or nose.
      Initially, the pain of the headaches lasted for seconds only and was brought on
      by coughing.

PMID- 14687014
TI  - Association between adolescent chronic daily headache and childhood adversity: a
      community-based study.
AB  - The relationship of chronic daily headache (CDH) and childhood adversity is still
      controversial. We therefore conducted a survey for CDH (> or =15 days/month,
      average > or = 2 h/day) among all students in three public schools in Taiwan. The
      Global Family Environment Scale (GFES), which yields a score according to
      childhood adverse events in the family, was used to compare childhood adversity
      between cases of CDH and their age- and sex-matched controls. In total, 4645
      students were surveyed and 58 with CDH were identified. Significantly lower GFES
      scores, indicative of worse childhood adversities, were evident in the CDH group
      (76.7 +/- 19.2), compared with the control group (86.0 +/- 8.9, P = 0.001).
      Physical abuse (10% vs. 0, P = 0.012) and parental divorce (17% vs. 3%, odds
      ratio = 5.8, P = 0.015) were more frequent in the CDH group. The results indicate
      that childhood adversities may contribute to greater risk of the development of
      CDH in young adolescents.

PMID- 14687015
TI  - Botulinum toxin A for chronic daily headache: a randomized, placebo-controlled,
      parallel design study.
AB  - Sixty patients with headaches of more than 15 days per month were recruited for
      this double-blind, placebo-controlled, parallel study of botulinum toxin type A
      (BTX) for chronic tension type and chronic migraine headaches. The primary
      efficacy point was the number of headache-free days as assessed by diary for 12
      weeks after BTX injection. Secondary efficacy points included global impressions,
      the use of abortive headache medications, and palpation. After recruitment,
      subjects kept diaries for 4 weeks prior to randomization, at which time they
      received either 200 U of BTX or matching placebo and were followed. After the
      week-12 evaluation, patients were offered 200 U of BTX (open label), and were
      similarly followed for another 12 weeks. The mean days with headache of the 60
      subjects (49 female, mean age 47 +/- 11 years) was 23 +/- 7 out of 30. Both
      groups were demographically similar (58 completed). Over a 12-week period after
      injections, headache-free days had improved in the BTX group from week 8 to 12 (P
      < 0.05), and strongly tended to improve over the entire 12-week period, 33 +/- 23
      vs. 24 +/- 16 days without headache (P = 0.07), but did not meet the a priori
      significance criteria. The subject global impressions (P < 0.05), subject change
      in headache impressions (P < 0.005), and investigator global impressions (P <
      0.001) all improved in the BTX group compared with placebo. Adverse events were
      mild and did not differ between groups. At week 24 (open label), headache-free
      days were less in the twice BTX injected group compared with the once injected
      group, 40 +/- 26 vs. 26 +/- 19 (P < 0.05). BTX may help chronic daily headache
      and appears to have a cumulative effect with subsequent injections. The treatment
      was very well tolerated.

PMID- 14687016
TI  - No evidence of cerebral oedema in severe acute mountain sickness.
AB  - In a randomized, double-blind cross-over study 10 subjects were exposed to a
      simulated altitude of 4500 m for 10 h after administration of placebo,
      acetozolamide (250 mg bid) or theophylline (250 mg bid). T2-weighted magnetic
      resonances images (MRI) and diffusion weighted MRI were obtained directly after
      exposure to altitude under hypoxic conditions. Although eight of 10 subjects had
      moderate to severe acute mountain sickness (AMS), we found no evidence of
      cerebral oedema, irrespective of the medication taken. Almost all subjects showed
      a decrease in inner cerebrospinal fluid (iCSF) volumes (placebo - 10.3%, P= 0.02;
      acetazolamide - 13.2%, P= 0.008, theophylline -12.2%, n.s.). There was no
      correlation between AMS symptoms and fluid shift. However, we found a
      significantly positive correlation of large (>10 ml) iCSF volume and more severe
      AMS after administration of placebo (r = 0.76, P= 0.01). Moderate to severe AMS
      after high altitude exposure for 10 h is associated with a decreased iCSF-volume
      independent of AMS severity or medication without signs of cerebral oedema.

PMID- 14687017
TI  - Migraine-tic syndrome: a case report of a new headache type.

PMID- 14687018
TI  - Retinal migraine as unusual feature of cerebral autosomal dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy (CADASIL).

PMID- 14687019
TI  - CNS effects of sumatriptan and rizatriptan.

PMID- 14687020
TI  - T-lymphoblastic lymphoma relapsing as acute myeloid leukaemia.

PMID- 14687021
TI  - An unusual presentation of chronic B-cell lymphocytic leukaemia.

PMID- 14687022
TI  - Molecular basis of mantle cell lymphoma.

PMID- 14687024
TI  - Diffuse large B-cell lymphoma: clinical implications of extranodal versus nodal
      presentation--a population-based study of 1575 cases.
AB  - Differences in genetic origin between nodal and extranodal diffuse large B-cell
      lymphomas (DLBCL) exist. Using population-based data from the registry of the
      Danish Lymphoma Group, the present study is the first to analyse clinical
      implications of nodal versus extranodal presentation of DLBCL. Of 4786 newly
      diagnosed non-Hodgkin's lymphoma patients in a 16-year period, 1575 (33%) had
      DLBCL. The annual incidence rate was 2.9 per 100 000; 40% were extranodal. The
      clinical profile of patients with extranodal DLBCL was different from the nodal
      DLBCL patients. Extranodal DLBCL was associated with older age and poorer
      performance score, but also lower tumour burden. In extranodal DLBCL, 51% of the
      cases were stage I and 36% were stage IV, whereas the patients were relatively
      equally distributed between the four stages in nodal DLBCL. For stage I patients,
      extranodal DLBCL was independently associated with poor survival (P = 0.003). In
      contrast, among stage IV patients those with extranodal DLBCL survived longer (P
      = 0.009). We conclude that there are important clinical differences between nodal
      and extranodal DLBCL. The addition of these clinical results to the existing
      aetiological and genetic data suggests that the distinction between nodal and
      extranodal DLBCL is not only pathogenetically but also clinically important.

PMID- 14687023
TI  - Long-acting beta2-adrenergic formoterol and salmeterol induce the apoptosis of B
      chronic lymphocytic leukaemia cells.
AB  - B-cell chronic lymphocytic leukaemia (B-CLL) is a neoplastic disorder
      characterized by defective apoptosis, cell accumulation in G0/G1, and high
      expression of BCL2 oncogene. Intracellular cyclic adenosine monophosphate (cAMP)
      accumulation increases the chemosensitivity of B-CLL cells in vitro and in vivo.
      In the present study, we investigated the effects of beta2-adrenergic compounds,
      well known cAMP-inducing drugs, on the in vitro survival of leukaemia cells. In
      contrast to the short-acting beta2-mimetic (beta2Mim) salbutamol, a consistent
      pro-apoptotic effect was observed with the long-acting beta2Mim salmeterol and
      formoterol. Normal B cells isolated from control donors were totally resistant to
      the above molecules. These compounds also increased chlorambucil- and fludarabine
      induced death of B-CLL cells. Blockade of beta-adrenergic receptor signalling or
      cAMP did not alter B-CLL apoptosis with beta2 Mimagents. Leukaemia cell apoptosis
      by beta2Mim correlated with an increase in calcium influx, decreased bcl-2
      protein and mRNA levels, increase in BAX gene expression and a marked rise in
      BCL2/BAX mRNA ratios. Interleukin-4, a cytokine that increases bcl-2 expression
      in B-CLL cells, rescued leukaemia cell from apoptosis with beta2Mim. These data
      show that long-acting beta2-adrenergic agents promote apoptotic leukaemia cell
      death through an adrenoreceptor- and cAMP-independent, Ca2+-dependent mechanism.

PMID- 14687025
TI  - BAT-25 and BAT-26, two mononucleotide microsatellites, are not sensitive markers
      of microsatellite instability in acute myeloid leukaemia.
AB  - BAT-25 and BAT-26 are mononucleotide microsatellites with quasi-monomorphic
      allele length distribution in healthy controls but unstable, shortened alleles in
      solid organ tumours with a mutator phenotype (RER+). Both markers are highly
      sensitive and specific for RER+ colorectal cancer. This study evaluated three
      mononucleotide microsatellites, BAT-25, BAT-26 and BAT-40 (a polymorphic
      mononucleotide microsatellite) in RER+ acute myeloid leukaemia (AML). Sixteen
      [six therapy-related AML (t-AML), 10 de novo AML] known RER+ AML, 22 healthy
      controls and five known RER- AML samples were analysed. In healthy controls and
      RER- AML, BAT-25 and BAT-26 were quasi-monomorphic and BAT-40 was polymorphic. Of
      the RER+ AML samples, 0 of 16 had microsatellite instability (MSI) at BAT-25, 0
      of 16 had MSI at BAT-26 and three of 16 had MSI at BAT-40. We conclude that BAT
      25, BAT-26 and BAT-40 microsatellites are insensitive to RER+ AML. Further
      studies are required to determine a consensus panel of sensitive microsatellites
      for use in AML.

PMID- 14687026
TI  - Apicidin potentiates the imatinib-induced apoptosis of Bcr-Abl-positive human
      leukaemia cells by enhancing the activation of mitochondria-dependent caspase
      cascades.
AB  - Apicidin, a histone deacetylase inhibitor, is a novel cyclic tetrapeptide with
      potent antiproliferative activity against various cancer cells. We examined
      whether apicidin potentiates the imatinib-induced apoptosis of Bcr-Abl-positive
      human leukaemia cells. In K562 cells, the co-administration of minimally toxic
      concentrations of imatinib and apicidin (imatinib/apicidin) for 48 h produced a
      marked increase in mitochondrial damage, processing of caspase cascades and
      apoptosis. Similar results were observed in leukaemic blasts obtained from
      patients with chronic myeloid leukaemia in blast crisis. Imatinib/apicidin co
      treatment for 48 h resulted in a near complete loss of the full-length XIAP (X
      linked inhibitor of apoptosis) protein, with a corresponding increase in the 29
      kDa XIAP cleavage product. Both the degradation of XIAP and increased release of
      second mitochondria-derived activator of caspase/direct IAP-binding protein with
      low pI (Smac/DIABLO) into the cytosol were abrogated by pretreatment with the
      caspase-3 inhibitor DEVD-CHO. Imatinib/apicidin co-treatment for 48 h produced a
      prominent decrease in Bcr-Abl protein levels in a caspase-dependent manner. In
      summary, these data indicate that apicidin potentiates the imatinib-induced
      apoptosis of Bcr-Abl-positive leukaemia cells through the enhanced activation of
      the mitochondria-dependent caspase cascades, accompanied by caspase-dependent
      downregulation of Bcr-Abl and XIAP. These findings generate a rationale for
      further investigation of apicidin and imatinib as a potential therapeutic
      strategy in Bcr-Abl-positive leukaemias.

PMID- 14687027
TI  - Altered expression of Tfg and Dap3 in Ikaros-defective T-cell lymphomas induced
      by X-irradiation in B6C3F1 mice.
AB  - Ikaros is a Kruppel-type zinc finger protein that is essential for normal
      lymphocyte development and differentiation. Recently, it has been demonstrated
      that Ikaros is frequently inactivated in both human and mouse
      leukaemias/lymphomas. Although this inactivation is thought to be involved in
      leukaemogenesis, little is known about the molecular mechanisms that lead to
      neoplastic transformation. To identify the genes that may be controlled by
      Ikaros, we performed differential display analysis of RNAs from mouse 3T3-L1
      cells that had been transfected with the Ikaros gene. Two cDNAs, the Trk-fused
      gene (Tfg) and death-associated protein 3 gene (Dap3) were upregulated in Ikaros
      transfected cells. Expression of Tfg and Dap3 was consistently downregulated in
      radiation-induced T-cell lymphomas that exhibited defective Ikaros expression.
      These results suggest that Tfg and Dap3 function downstream of Ikaros and may be
      involved in radiation-induced lymphomagenesis.

PMID- 14687028
TI  - The role of mitochondrial targeting in arsenic trioxide-induced apoptosis in
      myeloid cell lines.
AB  - Data regarding the role of mitochondria in arsenic trioxide (As2O3)-induced
      apoptosis are controversial. We investigated the contribution of caspases and
      mitochondrial depolarization to As2O3-induced apoptosis in the myeloid cell lines
      NB-4, HL-60 and U-937. Caspase inhibition reduced the amount of cells with As2O3
      (20 micromol/l)-induced mitochondrial depolarization by about 50% in all cell
      lines. As2O3 also induced dose-dependent phosphatidylserine exposure in cells
      without depolarized mitochondria. We conclude that caspase activation is of
      similar importance in As2O3-induced apoptosis in myeloid cell lines as direct
      mitochondrial targeting and mitochondria are not necessary for caspase activation
      downstream of mitochondria.

PMID- 14687029
TI  - Elevation of serum hepatocyte growth factor during granulocyte colony-stimulating
      factor-induced peripheral blood stem cell mobilization.
AB  - We examined serum levels of the angiogenic factors, vascular endothelial growth
      factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth
      factor (HGF), in normal donors for allogeneic peripheral blood stem cell (PBSC)
      transplantation. Granulocyte colony-stimulating factor (G-CSF) (filgrastim 400
      microg/m2/d) was administered to 23 donors for 5 d and aphereses were performed
      on days 4 and 5. Although bFGF remained at similar levels after G-CSF treatment,
      serum VEGF and HGF levels increased 1.5-fold (n = 13; P = 0.02) and 6.8-fold (n =
      23; P < 0.0001) respectively. The serum HGF level before G-CSF administration on
      day 1 correlated inversely with mobilized CD34+ cell numbers. Time course
      kinetics of HGF showed that on the day after G-CSF administration (day 2), serum
      HGF levels increased to 3678 pg/ml. For auto PBSC mobilization with chemotherapy
      and G-CSF 200 microg/m2/d (n = 8), we observed similar HGF elevation, which
      appeared to be dose-dependent on the G-CSF administered.

PMID- 14687030
TI  - Filgrastim-induced stem cell mobilization in chronic myeloid leukaemia patients
      during imatinib therapy: safety, feasibility and evidence for an efficient in
      vivo purging.
AB  - Therapy with imatinib mesylate is limited by cellular resistance in chronic
      myeloid leukaemia (CML). Further, the limited availability of matching stem cell
      donors or an unfavourable risk profile for allogeneic stem cell transplantation
      (SCT) reduces the number of therapeutic options in a number of patients. To
      assess the possibility of stem cell mobilization (SCM) during imatinib therapy we
      performed granulocyte colony-stimulating factor (filgrastim)-induced SCM and
      subsequent aphaeresis in 15 chronic phase and three accelerated phase CML
      patients. Aphaeresis was successful in 13 patients (72%) (> or =2.0 x 10(6) CD34+
      cells/kg body weight) and five (28%) harvests could be obtained, which were
      negative for BCR/ABL mRNA as assessed by nested-reverse transcription polymerase
      chain reaction (RT-PCR). All harvests, except one, were negative after first
      round RT-PCR, implicating a low level of CML cell contamination. There was no
      significant change in peripheral BCR/ABL transcript load after SCM as assessed by
      quantitative real-time RT-PCR. Fifteen patients remained stable in complete
      cytogenetic remission (CCR) during a median observation period of 9.3 months. One
      patient achieved a molecular remission shortly after SCM. Another patient who
      exhibited rising BCR/ABL mRNA levels before SCM achieved CCR after autologous SCT
      with the generated harvest. One patient with a Philadelphia chromosome-negative,
      BCR/ABL-positive CML showed a cytogenetic relapse 6 months after SCM. We conclude
      that filgrastim-induced CD34+ cell aphaeresis under simultaneous imatinib
      medication is safe and feasible in CML patients. Additionally, we found evidence
      that this procedure could generate stem cell harvests that exhibit non-detectable
      levels of BCR/ABL mRNA.

PMID- 14687031
TI  - Thienopyridine-linked thrombotic microangiopathy: association with endothelial
      cell apoptosis and activation of MAP kinase signalling cascades.
AB  - The thienopyridine platelet antagonist ticlopidine is associated with development
      of thrombotic thrombocytopenic purpura (TTP) but the pathophysiology of this link
      is unclear. Severe deficiency of disintegrin and metalloproteinase with
      thrombospondin motif-13 (ADAMTS13), described in familial cases and a significant
      fraction of idiopathic TTP, has been reported in only a few ticlopidine-linked
      cases. As ticlopidine can disrupt production of extracellular matrix (ECM)
      components critical to microvascular endothelial cell (MVEC) integrity in vitro,
      we explored the hypotheses that ticlopidine and ticlopidine-linked TTP plasmas
      induce MVEC apoptosis in a manner similar to that of idiopathic TTP plasmas, and
      that ECM components and related mitogen-activated protein kinase (MAPK)
      signalling cascades may be involved in this process. Replicating the activity of
      plasmas from patients with idiopathic TTP, plasma from five ticlopidine-linked
      TTP patients induced apoptosis of primary human dermal, glomerular and hepatic
      MVEC, but had no effect on pulmonary MVEC or large vessel endothelial cells (EC).
      Pharmacological levels of ticlopidine initiated apoptosis with similar EC lineage
      restriction. In parallel, ticlopidine and plasmas from idiopathic and ticlopidine
      TTP patients decreased transcripts for the ECM component thrombospondin-1 in
      MVEC, but not in large vessel EC. These changes were accompanied by prolonged
      induction of MAPKs extracellular signal-related kinase (ERK)-1/2 and p38 only in
      TTP susceptible MVEC. Induction of apoptosis by ticlopidine and TTP plasma was
      abrogated by inhibitors of ERK-1/2 and p38 phosphorylation. In conclusion, MVEC
      apoptosis related to altered ECM-MVEC interactions may be a key part of the
      pathology of ticlopidine-linked and idiopathic TTP.

PMID- 14687032
TI  - Decrease of Smad4 gene expression in patients with essential thrombocythaemia may
      cause an escape from suppression of megakaryopoiesis by transforming growth
      factor-beta1.
AB  - Essential thrombocythaemia (ET) is characterized by the abnormal and sustained
      proliferation of megakaryocytes. The mechanism for this lineage-specific
      expansion in ET, remains unclear. We have previously reported that transforming
      growth factor-beta1 (TGF-beta1) is involved in negative feedback regulation of
      megakaryopoiesis in both healthy volunteers (HV) and patients with idiopathic
      thrombocytopenic purpura (ITP). The present study found that megakaryocyte colony
      forming units (CFU-MK) of ET patients were less sensitive to TGF-beta1 than those
      of HV. The expression of Smad4 (Sma- and Mad-related protein-4) in CFU-MK of ET
      patients was reduced in comparison with that of HV. Finally, to confirm that the
      impaired TGF-beta1 sensitivity was caused by reduced expression of Smad4, we
      examined Smad4-transfected CFU-MK from ET patients in the presence of TGF-beta1,
      and verified that the transfectants were indeed as susceptible as CFU-MK from HV
      to TGF-beta1. Thus it was surmised that one of the mechanisms for impaired
      sensitivity of CFU-MK to TGF-beta1 is the reduced expression of Smad4.

PMID- 14687033
TI  - A rapid and specific whole blood HPA-1 phenotyping by flow cytometry using two
      commercialized monoclonal antibodies directed against GP IIIa and GP IIb-IIIa
      complexes.
AB  - The human platelet antigen 1 (HPA-1) system has been implicated in rare but
      severe diseases, such as neonatal alloimmune thrombocytopenic purpura, post
      transfusion purpura and immune platelet refractoriness. We developed a flow
      cytometry assay for HPA-1 phenotyping using two commercial monoclonal antibodies,
      P2 and SZ21, directed against glycoprotein (GP) IIb-IIIa and GP IIIa
      respectively. One hundred and twenty-seven healthy controls were studied and
      ratios of mean fluorescence intensity for P2 and SZ21 discriminated between HPA
      1a homozygotes and heterozygotes. These two monoclonal antibodies, coupled with
      flow cytometry represent a rapid and reliable tool for platelet HPA-1 typing to
      aid diagnosis.

PMID- 14687034
TI  - Beta+45 G --> C: a novel silent beta-thalassaemia mutation, the first in the
      Kozak sequence.
AB  - A family from the Southeast of Italy was found to have a novel beta-globin
      mutant, beta+45 G-->C, with the features of a silent beta-thalassaemia mutation.
      It was asymptomatic in two heterozygotes, but its interaction with the severe
      thalassaemia mutation beta-IVS-II-654 C-->T worsened the haematological and
      biosynthetic phenotype in two compound heterozygotes; moreover, another compound
      heterozygote, who was also heterozygote for the alphaalphaalpha(anti3.7),
      suffered from thalassaemia intermedia. The mutation was found associated in cis
      with the IVS-II-754 T-->C substitution, which did not lead to abnormally spliced
      mRNA. Furthermore, the amount of beta+45 mRNA was the same as the betaA mRNA in
      the reticulocytes of the carriers. In vitro transcription/translation experiments
      demonstrated that the beta+45 G-->C decreased the efficiency of translation of
      the beta-globin chain by about 30%: this slight impairment was consistent with
      the observed clinical phenotype. The beta+45 G-->C is the first mutation found in
      the Kozak sequence (GACACCATGG) of the beta-globin gene and the first one at the
      position -6 upstream the ATG. The Kozak consensus sequence plays a major role in
      the initiation of translation process. The present finding supports the
      hypothesis that the G in position -6 is important in this process.

PMID- 14687035
TI  - A thalassaemia array for Southeast Asia.
AB  - The alpha and beta thalassaemias are the commonest genetic disorders worldwide.
      The homozygous state is associated with high morbidity and mortality, thus
      screening of at-risk pregnancies and prenatal testing are strongly advocated. A
      thalassaemia (thal) array has been designed using allele-specific arrayed primer
      extension (AS-APEX) for the simultaneous analysis of 15 non-deletion alpha-gene
      defects and 23 beta-gene mutations commonly found in southeast Asian countries,
      where thalassaemias are highly prevalent. This overcomes the problem of using
      multiple reverse dot blot analysis. The array showed 100% sensitivity and
      specificity in the detection of 120 beta-thal mutants and 35 non-deletion alpha
      thal mutants. It is robust enough to be produced in a single place and shipped to
      other laboratories for use. The production cost of the array is low, each slide
      can be used for three different test samples and is therefore amenable to large
      scale antenatal screening in southeast Asian countries.

PMID- 14687036
TI  - Association of T-786C eNOS gene polymorphism with increased susceptibility to
      acute chest syndrome in females with sickle cell disease.
AB  - Acute chest syndrome (ACS) is a life-threatening complication of sickle cell
      disease (SCD). A retrospective study was performed to evaluate the role of
      endothelial nitric oxide synthase (eNOS) gene polymorphisms (E298D and T-786C) in
      African-American SCD patients. The D298 allele showed no association; the C-786
      allele showed a statistically significant association (P = 0.0061) in female ACS
      cases. Multiple logistic regression analysis showed that relative risk of ACS was
      8.695 (P = 0.0076, 95% confidence interval 1.761-42.920) for female carriers of C
      786. eNOS T-786C is a gender-specific genetic modifier that is associated with
      increased susceptibility to ACS in female SCD patients.

PMID- 14687037
TI  - The value of alloantibody detection in predicting response to HLA-matched
      platelet transfusions.
AB  - Alloantibody tests demonstrate immunological causes of insufficient increments in
      random platelet transfusions. The value of a positive or negative test result in
      predicting the outcome of human leucocyte antigen (HLA)-matched transfusions in
      patients refractory to leucodepleted random platelet transfusions has not been
      assessed. We retrospectively evaluated the outcome of the first HLA-matched
      platelet transfusion in 72 patients with haematological diseases in two ways:
      first, the strategy according to which the patient was selected for HLA-matched
      platelet transfusions was analysed. The strategies were: (i) results of
      alloantibody tests were not available, (ii) a positive alloantibody test, (iii) a
      negative alloantibody test. Secondly, the outcome of the first HLA-matched
      transfusion was investigated relative to the results of alloantibody tests,
      irrespective of the decision strategy. No significant association was found
      between the decision strategy and the outcome of the first HLA-matched platelet
      transfusion. Positive alloantibody tests, however, predicted a better outcome of
      the first HLA-matched platelet transfusion (P = 0.04 and P = 0.03 after 1 and 16
      h respectively). In patients refractory to random platelet transfusions, positive
      alloantibody tests predicted a better outcome of HLA-matched platelet
      transfusions. Patients with negative alloantibody tests, however, may benefit
      from HLA-matched platelet transfusions.

PMID- 14687038
TI  - Hereditary pyropoikilocytosis and the spectrin St. Claude allele.

PMID- 14687039
TI  - Systematic screening for HCV infection should be performed in patients with
      splenic marginal zone lymphoma.

PMID- 14687040
TI  - Elevated serum cobalamin levels in childhood autoimmune and drug-induced
      neutropenia.

PMID- 14687043
TI  - The use of Zelen's design in randomised trials.

PMID- 14687044
TI  - Recruitment to multicentre trials.

PMID- 14687045
TI  - Epidemiology of menstrual disorders in developing countries: a systematic review.

PMID- 14687046
TI  - A randomised controlled trial of ursodeoxycholic acid and S-adenosyl-l-methionine
      in the treatment of gestational cholestasis.
AB  - OBJECTIVE: To compare the efficacy of S-adenosyl-l-methionine and ursodeoxycholic
      acid in improving serum biochemical abnormalities in gestational cholestasis.
      DESIGN: Randomised clinical trial. SETTING: University hospital. POPULATION: All
      women at <36 weeks of gestation with severe gestational cholestasis during June
      1996 to December 2001. METHODS: Enrolled women were randomly assigned oral S
      adenosyl-l-methionine 500 mg twice daily or oral ursodeoxycholic acid 300 mg
      twice daily until delivery. MAIN OUTCOME MEASURES: Reduction in the concentration
      of serum bile acids. Other variables considered included obstetric and neonatal
      outcome, clinical symptoms and other laboratory measurements (serum levels of
      transaminases and bilirubin). The two groups were compared using Student's t
      test, Wilcoxon's signed rank sum test and Fisher's exact test, with a two-tailed
      P < 0.05 being considered significant. RESULTS: Of the 46 women enrolled, 24
      received ursodeoxycholic acid and 22 S-adenosyl-l-methionine. At enrolment,
      gestational age, duration of therapy, rate of nulliparity, pruritus score and
      biochemical characteristics were similar between the groups. Both therapies
      significantly and equally improved pruritus. Women receiving ursodeoxycholic acid
      had a significantly greater improvement in the concentration of serum bile acids
      (P= 0.001), aspartate aminotransferase (P= 0.01), alanine aminotransferase
      (<0.001) and bilirubin (P= 0.002) compared with those receiving S-adenosyl-l
      methionine. Duration of therapy was significantly greater in women receiving
      ursodeoxycholic acid compared with S-adenosyl-l-methionine (P= 0.04), whereas
      gestational age at delivery and rate of prematurity were similar in the two
      groups. CONCLUSIONS: In women with intrahepatic cholestasis of pregnancy,
      ursodeoxycholic acid is more effective than S-adenosyl-l-methionine at improving
      the concentration of serum bile acids and other tests of liver function, whereas
      both therapies are equally effective at improving pruritus.

PMID- 14687047
TI  - Monoamniotic twin pregnancies: antenatal management and perinatal results of 19
      consecutive cases.
AB  - OBJECTIVE: To describe the obstetric management and perinatal outcome of
      antenatally diagnosed monoamniotic twin pregnancies (MATP) in a tertiary level
      maternity unit. SETTING: Port-Royal Maternity Hospital, Paris, France.
      POPULATION: MATP that progressed beyond 22 weeks seen from 1993 to 2001. METHODS:
      A retrospective chart review of all twin pregnancies. Diagnosis of MATP was made
      by ultrasonography and confirmed by placental pathology. MAIN OUTCOME MEASURE:
      Perinatal mortality. RESULTS: Among the 1242 twins pregnancies delivered during
      the study period, 19 were monoamniotic. Four fetuses (10% of all births) had
      malformations. Perinatal mortality was high (n= 12, 32%) because of fetal deaths
      (nine cases) and very preterm births (three neonatal deaths). No fetal deaths
      occurred after 29 weeks. Of the 15 women with at least one live fetus before
      labour, 6 gave birth by vaginal delivery (40%). No obstetric accidents occurred
      during vaginal deliveries. CONCLUSION: Perinatal mortality of MATP is still very
      high, even with accurate, early antenatal diagnosis, intensified surveillance and
      delivery provided in a tertiary level hospital. The main causes of perinatal
      deaths are cord accidents in utero, congenital anomalies and very preterm births.

PMID- 14687048
TI  - The sex ratio of pregnancies complicated by hospitalisation for hyperemesis
      gravidarum.
AB  - OBJECTIVE: To evaluate the sex ratio among pregnancies complicated by first
      trimester hyperemesis gravidarum and extend previous findings to include a
      measure of severity. DESIGN: Population-based case control study. SETTING: All
      non-federal hospitals in Washington State. POPULATION: Two thousand and one
      hundred and ten pregnant women hospitalised for hyperemesis gravidarum and 9783
      pregnant women without hyperemesis gravidarum. METHODS: The infant sex ratio for
      pregnant women admitted to the hospital for hyperemesis gravidarum was evaluated
      using the Washington State hospital discharge database linked to the birth
      certificate database for years 1987-1996. Cases were pregnant women hospitalised
      for hyperemesis gravidarum (International Classification for Diseases-9th edition
      [ICD-9] diagnosis code 643) in the first trimester. Controls were women who
      experienced a singleton live birth and were not hospitalised for hyperemesis in
      Washington State during the same time period. Regression analysis with general
      estimating equations was used to calculate an odds ratio (OR) and 95% confidence
      interval (CI) to assess the association of hyperemesis gravidarum with infant sex
      ratio. MAIN OUTCOME MEASURE: Infant sex ratio. RESULTS: Pregnant women
      hospitalised for hyperemesis gravidarum in the first trimester had a 50%
      increased odds of having a female infant compared with controls (OR 1.5, 95% CI
      1.4, 1.7). Women hospitalised for three or more days had the greatest odds of
      having a female infant compared with control women (OR 1.8, 95% CI 1.5, 2.0).
      CONCLUSION: Hyperemesis gravidarum is associated with an increase in female live
      births and may be a marker for high oestrogen levels in utero.

PMID- 14687049
TI  - Birthweight by gestational age in preterm babies according to a Gaussian mixture
      model.
AB  - OBJECTIVE: To provide a statistically sound criterion for identifying implausibly
      large birthweights for gestational age. DESIGN: Review of ISTAT 1990-1994
      national newborn records. SETTING: Italy POPULATION: Forty-two thousand and
      twenty-nine single first and second liveborn preterm babies. METHODS: Two
      component Gaussian mixture models are used to describe the birthweight
      distributions stratified by gestational age. Implausibly large babies are
      identified through model-based probabilistic clustering. MAIN OUTCOME MEASURES:
      Gestational age misclassification and weight-for-gestational age centile curves
      RESULTS: Gestational age appears under-estimated by about six weeks in 12.3% of
      the cases. Large babies are equally present in males and females, but are more
      frequent in second-borns than in first-borns, even when parity-specific models
      are fitted. CONCLUSIONS: The approach allows for a quantification of the
      gestational age under-estimate error and for data correction through model-based
      clustering. Correct birthweight distributions and growth curves are also
      provided.

PMID- 14687050
TI  - Automated self-initiated blood pressure or 24-hour ambulatory blood pressure
      monitoring in pregnancy?
AB  - OBJECTIVE: To determine whether self-initiated and recorded automated blood
      pressure measurement can provide an accurate estimate of ambulatory blood
      pressure in pregnant women suspected of having 'white coat hypertension'. DESIGN:
      A prospective observational study. SETTING: Women's and Children's Health Unit,
      St George Hospital, a teaching hospital of the University of New South Wales.
      POPULATION: Pregnant women being assessed for possible 'white-coat hypertension'.
      METHODS: Sixty-six pregnant women who were undergoing 24 hour ambulatory blood
      pressure monitoring (ABPM) in their home or work environment also measured their
      blood pressure six times during this interval using a self-initiated automated
      blood pressure recorder (Omron HEM 705CP). Agreement between awake ABPM and Omron
      recorded blood pressures was tested by Bland-Altman analysis. MAIN OUTCOME
      MEASURE: Limits of agreement between blood pressures measured by each device.
      RESULTS: Average blood pressures obtained by the two devices were identical
      (125/77 mmHg) but limits of agreement were wide, -20 to +23 mmHg for systolic
      blood pressure and -9 to +15 mmHg for diastolic blood pressure. CONCLUSION: The
      Omron HEM 705CP is a useful device for measuring group average blood pressures in
      pregnant women suspected of having white coat hypertension but cannot reliably
      replace ABPM for clinical management of individual pregnant women.

PMID- 14687051
TI  - A randomised trial comparing low dose vaginal misoprostol and dinoprostone for
      labour induction.
AB  - OBJECTIVE: To compare vaginal misoprostol with dinoprostone for induction of
      labour. DESIGN: Randomised multicentre trial. SETTING: Labour wards of one
      university hospital and two teaching hospitals. POPULATION: Six hundred and
      eighty-one women with indication for labour induction at >or=36 weeks of
      gestation, singleton pregnancy and no previous ceasarean section. METHODS:
      Misoprostol (25 mcg, hospital-prepared capsule) in the posterior vaginal fornix,
      every four hours, maximum three times daily or dinoprostone gel (1 mg) every four
      hours. Oxytocin was administered if necessary. MAIN OUTCOME MEASURES: Primary:
      'adverse neonatal outcome' (5-minute Apgar score <7 and/or umbilical cord pH
      <7.15). Secondary: labour duration, mode of delivery and patient satisfaction.
      RESULTS: Three hundred and forty-one women received misoprostol and 340
      dinoprostone. The median induction-delivery interval was longer in the
      misoprostol group compared with the dinoprostone group (25 versus 19 hours, P=
      0.008). The caesarean section rate was lower in the misoprostol group:
      16.1%versus 21%, but this difference was not statistically significant RR = 0.8
      (95% CI 0.6-1.04). 'Adverse neonatal outcome' was found to be similar in both
      groups: 21% in the misoprostol and 23% in the dinoprostone groups. Significantly
      fewer neonates were admitted to NICU in the misoprostol group compared with
      dinoprostone 19%versus 26% (RR = 0.7, 95% CI 0.5-0.98). CONCLUSIONS: Misoprostol
      in this dosing regimen is a safe method of labour induction. NICU admission rates
      were lower in the misoprostol group. No difference could be detected in patient
      satisfaction between groups.

PMID- 14687052
TI  - A randomised controlled trial comparing abdominal and vaginal prolapse surgery:
      effects on urogenital function.
AB  - OBJECTIVE: To compare the effects of vaginal hysterectomy (combined with anterior
      and/or posterior colporraphy) and abdominal sacro-colpopexy (with preservation of
      the uterus) on urogenital function. DESIGN: Randomised trial. SETTING: Three
      teaching hospitals in The Netherlands. POPULATION: Eighty-two patients undergoing
      surgical correction of uterine prolapse stages II-IV. METHODS: Participating
      patients completed the urogenital distress inventory (UDI), before and at six
      weeks, six months and one year after surgery, to measure discomfort of prolapse
      and micturition symptoms. Domain scores of the UDI (ranging from 0 to 100, higher
      scores indicating more discomfort) were compared between groups at all time
      points. Findings at pelvic examination, number of doctor visits within the first
      year after surgery because of pelvic floor symptoms and performed or planned
      surgery of recurrent genital prolapse were also compared. MAIN OUTCOME MEASURE:
      Domain scores of the UDI at one year after surgery. RESULTS: At one year after
      surgery, scores on the discomfort/pain domain (mean difference 7.1, 95%
      confidence interval [CI] 1.1-13.2), overactive bladder domain (mean difference
      8.7, 95% CI 0.5-16.9) and obstructive micturition domain (mean difference 10.3,
      95% CI 0.6-20.1) of the UDI were significantly higher in the abdominal group than
      in the vaginal group. Findings at pelvic examination were similar in both groups.
      Doctor visits because of pelvic floor symptoms were more frequent in the
      abdominal group than in the vaginal group. Re-operation was performed or planned
      in 9 of the 41 patients who underwent abdominal surgery and in 1 of the 41
      patients who underwent vaginal surgery (odds ratio [OR] = 11.2, 95% CI 1.4-90.0).
      CONCLUSIONS: Our findings suggest that vaginal hysterectomy with anterior and/or
      posterior colporraphy is preferable to abdominal sacro-colpopexy with
      preservation of the uterus as surgical correction in patients with uterine
      prolapse stages II-IV.

PMID- 14687053
TI  - Randomised comparison of distension media for outpatient hysteroscopy.
AB  - OBJECTIVE: To compare saline with and without added lignocaine and carbon dioxide
      distension for out patient hysteroscopy with regards to patient discomfort and
      hysteroscopic view. DESIGN: Single blind prospective randomised controlled trial.
      SETTING: Specialist out patient clinics in a large teaching hospital. POPULATION:
      Women undergoing out patient hysteroscopy and endometrial biopsy for abnormal
      uterine bleeding. METHOD: Out patient hysteroscopy using carbon dioxide, saline
      or saline with lignocaine. MAIN OUTCOME MEASURES: Visual analogue score (VAS) for
      pain and present pain intensity (PPI) as assessed by patients and the quality of
      hysteroscopic view as assessed by the operator. RESULTS: Of the 305 women
      approached, 300 women were randomised into the study. The mean [SD] VAS for pain
      in the carbon dioxide group was 2.9 [2.3] and in the saline group was 3.1 [2.6],
      the difference was not statistically significant (P= 0.49). The mean [SD] VAS for
      pain in the saline plus lignocaine group was 3.2 [2.4]. This was not
      significantly different from the saline group (P= 0.72). There was a
      statistically significant difference between the confidence rating for the
      hysteroscopic view for the carbon dioxide compared with the saline group; mean
      [SD] was 8.3 [2.1] and 9.6 [1.1], respectively (P= 0.001). CONCLUSION: Carbon
      dioxide and saline as distension media are comparable in terms of overall patient
      discomfort and satisfaction, but saline provides better views and increases
      confidence in diagnosis. Adding lignocaine to the saline distension medium does
      not confer any additional benefit.

PMID- 14687054
TI  - A randomised controlled trial of cytological surveillance versus patient choice
      between surveillance and colposcopy in managing mildly abnormal cervical smears.
AB  - OBJECTIVE: To determine whether choice of colposcopy or six month cytological
      surveillance would be beneficial to women with mildly abnormal smears when
      compared with the national policy of six months surveillance in terms of
      psychological morbidity. DESIGN: A randomised trial based on the Zelen design.
      SETTING: A hospital-based research clinic. POPULATION: Four hundred and seventy
      six women who had had a recurrent borderline or mildly dyskaryotic smear on
      routine cervical screening in primary care. METHODS: Women were randomised either
      to six months cytological surveillance or to make a choice between that or
      colposcopy and were followed up for 1 year. MAIN OUTCOME MEASURES: The primary
      outcome measure was caseness (score >or=4) on the General Health Questionnaire at
      12 months follow up. Other measures were the Spielberger State and Trait scores,
      default rates and cytology/colposcopy outcomes. RESULTS: There was no significant
      difference between the arms for General Health Questionnaire (GHQ) scores and
      Spielberger State and Trait at 12 months. There was a significant reduction in
      psychometric morbidity between baseline and 12 months in both arms. Overall rates
      of default from the protocol were the same in both arms, but default that led to
      uncertain ascertainment of cervical pathology was greater in the no-choice arm.
      CONCLUSIONS: This trial indicates that having choice did not impact favourably or
      harmfully on anxiety or feelings of wellbeing. If a patient is anxious, allowing
      the patient to choose immediate colposcopy may be preferable because it will
      improve ascertainment of underlying disease in a group who are more likely to
      default.

PMID- 14687055
TI  - Safety of birth centre care: perinatal mortality over a 10-year period.
AB  - OBJECTIVE: To study perinatal mortality in women booked for birth centre care
      during pregnancy. DESIGN: Retrospective cohort study. SETTING: In-hospital birth
      centre and standard maternity care in Stockholm. POPULATION: Two thousand and
      five hundred and thirty-four women (3256 pregnancies) admitted to an in-hospital
      birth centre over 10 years (1989-2000) and 126818 women (180380 pregnancies) who
      gave birth in standard care during the same period and who met the same medical
      inclusion criteria as in the birth centre. Multiple pregnancies were excluded.
      METHODS: Data were collected from the Swedish Medical Birth Register. Information
      on all cases of perinatal death in the birth centre group was retrieved from the
      medical records. MAIN OUTCOME MEASURE: Perinatal mortality. RESULTS: No
      statistically significant difference in the overall perinatal mortality rate was
      observed between the birth centre group and the standard care group (odds ratio
      [OR] 1.5, 95% CI 0.9-2.4), but infants of primiparas were at greater risk (OR
      2.2, 95% CI 1.3-3.9). Infants of multiparas tended to be at lower risk, but this
      difference was not statistically significant (OR 0.7, 95% CI 0.3-1.9). These
      figures were adjusted for maternal age and gestation in multiple regression
      analyses. CONCLUSION: Birth centre care may be less safe for infants of first
      time mothers.

PMID- 14687056
TI  - Routine ultrasound for pregnancy termination requests increases women's choice
      and reduces inappropriate treatments.
AB  - This prospective observational study aimed to determine the correlation between
      gestational age based on menstrual dates and ultrasound scan in women requesting
      pregnancy termination and the proportion of cases where first trimester medical
      termination might be offered. Two hundred and sixty-two women (93%) had ongoing
      pregnancies. Two hundred and thirty-seven women (90%) were certain of their
      menstrual dates but there was a discrepancy of more than one week in gestational
      age in 38%. Calculated from their menstrual dates, 138 women might have been
      offered first trimester medical termination but this rose to 173 if gestation was
      based on ultrasound scan. From this study, we believe ultrasound should be
      performed routinely for all women requesting pregnancy termination.

PMID- 14687057
TI  - Fetal short femur length in the second trimester and the outcome of pregnancy.
AB  - We reviewed 86 consecutive cases with fetal femur length (FL) below the 10th
      centile of our reference ranges at midtrimester ultrasonography. Three groups
      were identified based on perinatal outcome: normal infants (n= 28), newborns with
      structural and/or chromosomal anomalies (n= 40), small-for-gestational age (SGA)
      newborns (n= 18). Fetuses with skeletal dysplasias (n= 13) had significantly
      shorter FL. Aneuploidies were only found in fetuses with malformations other than
      skeletal dysplasias. The diagnosis of SGA, based on ultrasound abdominal
      circumference measurement <10th centile, was made 9 weeks (range 5-14) after the
      finding of a short FL. Half of these cases also developed pre-eclampsia.

PMID- 14687058
TI  - Horner's syndrome postpartum.

PMID- 14687059
TI  - Hysteroscopic diagnosis of interstitial ectopic pregnancy.

PMID- 14687060
TI  - Emergency contraception: the journey so far.

PMID- 14687061
TI  - Emergency contraception: the journey so far.

PMID- 14687062
TI  - Emergency contraception: the journey so far.

PMID- 14687063
TI  - Serum LH analysis: solutions and problems.

PMID- 14687064
TI  - Cerebral palsy and clinical negligence litigation: a cohort study.

PMID- 14687065
TI  - Factor V Leiden in pregnancies complicated by placental abruption.

PMID- 14687068
TI  - Advances in treatment of mood and anxiety disorders: focus on atypical
      antipsychotics.

PMID- 14687069
TI  - Preliminary linkage map of the turkey (Meleagris gallopavo) based on
      microsatellite markers.
AB  - The turkey is an agriculturally important species for which, until now, there is
      no published genetic linkage map based on microsatellite markers--still the
      markers most used in the chicken and other farm animals. In order to increase the
      number of markers on a turkey genetic linkage map we decided to map new
      microsatellite sequences obtained from a GT-enriched turkey genomic library. In
      different chicken populations more than 35-55% of microsatellites are
      polymorphic. In the turkey populations tested here, 43% of all turkey primers
      tested were found to be polymorphic, in both commercial and wild type turkeys.
      Twenty linkage groups (including the Z chromosome) containing 74 markers have
      been established, along with 37 other unassigned markers. This map will lay the
      foundations for further genetic mapping and the identification of genes and
      quantitative trait loci in this economically important species. Genome
      comparisons, based on genetic maps, with related species such as the chicken
      would then also be possible. All primer information, polymerase chain reaction
      (PCR) conditions, allele sizes and genetic linkage maps can be viewed at
      http://roslin.thearkdb.org/. The DNA is also available on request through the
      Roslin Institute.

PMID- 14687070
TI  - Feasibility and utility of microsatellite markers in archaeological cattle
      remains from a Viking Age settlement in Dublin.
AB  - Nineteen cattle bones from the Viking 10th and early 11th century levels in
      Dublin were assessed for presence of reliable genotypes from three autosomal
      markers. Due to the good preservational condition of the samples, it was possible
      to amplify and type at least two out of three of the microsatellite markers
      (CSRM60, HEL1 and ILSTS001) in 11 specimens. Full three-loci genotypes were
      obtained from a subset of seven of these samples. A comparative analysis was
      performed using data from the same three markers in 11 extant British, Irish and
      Nordic cattle breeds. Although the medieval remains displayed lower levels of
      diversity than the modern European breeds, the results fit within the ranges
      obtained from the extant populations. The results indicate a probable origin for
      the ancient Irish cattle as the remains group significantly more closely with
      breeds from the British Isles than with those from Scandinavia. The data
      collected indicate that microsatellites may be useful for the further study of
      ancient cattle.

PMID- 14687071
TI  - Mitochondrial DNA diversity of Pakistani goats.
AB  - Pakistan contains numerous domestic goat breeds, but until now there has been no
      comprehensive study on genetic diversity or a phylogenetic analysis of Pakistani
      goats. In this study, we analysed the complete mitochondrial DNA D-loop and the
      cytochrome b gene of 13 Pakistani domestic goat breeds (Capra hircus) and one
      wild goat, the Sindh Ibex (Capra aegagrus blythi). The phylogenetic analyses and
      sequence divergence (SD) established four distinct mt-lineages termed as A, B and
      C (previously reported) and a new lineage D. The Sindh Ibex appeared as an
      outgroup of domestic goats. The estimated divergence times between the most
      recently evolved mt-lineages A and D were from 260,483 to 371,052 YA. This
      suggested that at least four different strains of wild Capra might have been the
      source of the modern domestic goats. The new mt-lineage D revealed high SD from
      mt-lineage A and may be the oldest branch under domestication, while mt-lineages
      B and C showed lower SD and might have been domesticated during an advanced stage
      of the domestication process.

PMID- 14687072
TI  - Detection of QTL for immune response to sheep red blood cells in laying hens.
AB  - The aim of this study is to detect quantitative trait loci (QTL) involved in the
      regulation of the primary and the secondary immune response to sheep red blood
      cells (SRBC) in a resource population using microsatellite DNA markers. The F2
      resource population originates from a cross of two divergently selected lines for
      either high (H line) or low (L line) primary antibody response to SRBC. The F2
      population consisted of six half-sib families, three families per each of
      reciprocal crosses. Total antibody titres to SRBC were determined by
      agglutination in serum from all birds. F2, F1 and F0 generations were genotyped
      for 170 microsatellite markers, using a whole-genome scan approach. The half-sib
      and the line-cross analyses were performed to determine QTL regions associated
      with regulation of the immune response. In the half-sib analysis, four QTL for
      SRBC primary response have been identified: on GGA3, GGA5, GGA16 and GGA23. No
      QTL was identified for SRBC secondary response under the half-sib model. In the
      line-cross analysis, three QTL were identified on GGA10, GGA16 and GGA27 for SRBC
      primary response and five QTL were identified on GGA6, GGA9, GGA15, GGA16 and
      GGA27 for SRBC secondary response. Subsequently, the family contribution of
      individual families to the QTL was analysed. The family with the largest
      contribution was genotyped with additional microsatellite markers in the QTL
      region on GGA5. The extended half-sib analysis with additional genotype
      information results in narrowing down the QTL region on GGA5.

PMID- 14687073
TI  - Development of a single nucleotide polymorphism map of porcine chromosome 2.
AB  - Single nucleotide polymorphism markers are developed on SSC2, predominantly on
      the p-arm. Several studies reported a quantitative trait loci (QTL) for backfat
      thickness in this region. Single nucleotide polymorphisms were identified by
      comparative re-sequencing of polymerase chain reaction (PCR) products from a
      panel of eight individuals. The panel consisted of five Large Whites (each from a
      different Dutch breeding company), a Meishan, a Pietrain and a Wild Boar. In
      total, 67 different PCR products were sequenced and 301 SNPs were identified in
      32,429 bp of consensus sequence, an average of one SNP in every 108 bp. After
      correction for sample size, this polymorphism rate corresponds to a
      heterozygosity value of one SNP in every 357 bp. For 63% of the SNPs, there was
      variation among the five Large Whites, and these SNPs are relevant for linkage
      and association studies in commercial populations. Comparing the Whites with
      other breeds revealed higher variation rates with: (i) Meishan, 89%; (ii)
      Pietrain, 69%; (iii) Wild Boar, 70%. Because many of the experimental populations
      to identify QTL are based on crosses between these breeds, these SNPs are
      relevant for the fine mapping of the QTL identified within these crosses.

PMID- 14687074
TI  - Characterization of gene expression in double-muscled and normal-muscled bovine
      embryos.
AB  - Myostatin, a member of the transforming growth factor-beta superfamily, is a
      negative regulator of skeletal muscle growth. Cattle with mutations that
      inactivate myostatin exhibit a remarkable increase in mass of skeletal muscle
      called double muscling that is accompanied by an equally remarkable decrease in
      carcass fat. Although a mouse knockout model has been created which results in
      mice with a 200% increase in skeletal muscle mass, molecular mechanisms whereby
      myostatin regulates skeletal muscle and fat mass are not fully understood. Using
      suppressive subtractive hybridization, genes that were differentially expressed
      in double-muscled vs. normal-muscled cattle embryos were identified. Genetic
      variation at other loci was minimized by using embryonic samples collected from
      related Piedmontese x Angus dams or Belgian Blue x Hereford dams bred to a single
      sire of the same breed composition. Embryos were collected at 31-33 days of
      gestation, which is 2-4 days after high-level expression of myostatin in the
      developing bovine embryo. The suppressive subtraction resulted in 30 clones that
      were potentially differentially expressed, 19 of which were confirmed by
      macroarray analysis. Several of these genes have biological functions that
      suggest that they are directly involved in myostatin's regulation of skeletal
      muscle development. Furthermore, several of these genes map to quantitative trait
      loci known to interact with variation in the myostatin gene.

PMID- 14687075
TI  - Putative SNP discovery in interspecific hybrids of catfish by comparative EST
      analysis.
AB  - In this study, we identified putative SNP markers within genes by comparative
      analysis of expressed sequence tags (ESTs). Comparison of 849 ESTs from blue
      catfish (Ictalurus furcatus) with >11,000 ESTs from channel catfish (I.
      punctatus) deposited in GenBank resulted in the identification of 1020 putative
      SNPs within 161 genes, of which 145 were nuclear genes of known function. The
      observed frequency of SNPs within ESTs of the two closely related catfish species
      was 1.32 SNP per 100 bp. The majority of identified SNPs differed between the two
      species and, therefore, these SNPs are useful for mapping genes in channel
      catfish x blue catfish interspecific resource families. The SNPs that differed
      within species were also observed; these can be applied to genome scans in
      channel catfish resource families.

PMID- 14687076
TI  - Mapping of ESTs derived from pre-implantation stage cattle embryos to allocate 16
      new additions to the ordered comparative map of cattle and human.
AB  - Twenty expressed sequence tags (ESTs) derived from cDNA libraries of different
      developmental stages of embryos were mapped using a whole genome bovine hamster
      radiation hybrid panel. These include 14 markers representing genes, most of
      which have not so far been mapped in cattle, with another three being novel in
      both cattle and human. The markers were placed on specific chromosomes with high
      LOD scores and except two all localizations fit the current human and cattle
      comparative map. The assignment of these genes further enriches the cattle genome
      map and also contributes to the international effort of generating comparative
      maps.

PMID- 14687077
TI  - Fixed nucleotide differences on the Y chromosome indicate clear divergence
      between Equus przewalskii and Equus caballus.
AB  - The phylogenetic relationship between Equus przewalskii and E. caballus is often
      a matter of debate. Although these taxa have different chromosome numbers, they
      do not form monophyletic clades in a phylogenetic tree based on mtDNA sequences.
      Here we report sequence variation from five newly identified Y chromosome regions
      of the horse. Two fixed nucleotide differences on the Y chromosome clearly
      display Przewalski's horse and domestic horse as sister taxa. At both positions
      the Przewalski's horse haplotype shows the ancestral state, in common with the
      members of the zebra/ass lineage. We discuss the factors that may have led to the
      differences in mtDNA and Y-chromosomal observations.

PMID- 14687078
TI  - Characterization of the bovine BCL2L1 gene and related pseudogenes.
AB  - We have amplified and characterized partial regions of exons 2 and 3 of the
      bovine BCL2L1 gene, one of the anti-apoptotic members of the B-cell lymphoma 2
      gene family. Cloning and sequencing of the amplified products revealed the
      existence of several BCL2L1-related sequences, including the bovine BCL2L1 gene
      and various processed pseudogenes. The bovine BCL2L1 gene revealed two
      polymorphic nucleotide sequences that resulted in two protein variants, with
      amino acid replacements at positions 60 and 69. In addition, we report three
      bovine BCL2L1-related sequences (BCL2L1psi) that probably correspond to
      intronless processed pseudogenes. These BCL2L1psi pseudogene sequences have
      accumulated multiple substitutions, deletions and insertions that translated into
      stop codons or changed the open reading frame of the functional gene. We provide
      evidence suggesting that the retro-transposition event that originated these
      processed pseudogenes took place before the divergence of the Cervidae and
      Bovidae families.

PMID- 14687079
TI  - Population structure of the Southeast Asian river catfish Mystus nemurus.
AB  - A total of 143 microsatellites were isolated from Mystus nemurus using a 5'
      anchored polymerase chain reaction technique or the random amplified
      hybridization microsatellite method, the first set of microsatellite markers
      developed for the Southeast Asian river catfish. Twenty polymorphic
      microsatellite loci were used as markers for population characterization of M.
      nemurus from six different geographical locations in Malaysia (Perak, Kedah,
      Johor, UPM, Sarawak and Terengganu). The number of alleles per locus ranged from
      2 to 11 with 6.3 as the average number of alleles per locus. Characterization of
      the populations showed relatively high levels of genetic variation compared with
      previous studies using allozyme markers. The highest genetic similarity was found
      between Perak and Kedah, while the highest genetic distance was found between
      Terengganu and Kedah. The majority of clustering was in accordance with
      geographical locations and the histories of the populations. Microsatellite
      analysis indicated that the Sarawak population might be genetically closer to the
      Peninsular Malaysian populations than has been previously shown by other
      molecular marker studies.

PMID- 14687080
TI  - Characterization of the genetic diversity on natural populations of Chinese
      miniature pig breeds.

PMID- 14687081
TI  - Fine mapping of the bovine heart fatty acid-binding protein gene (FABP3 ) to
      BTA2q45 by fluorescence in situ hybridization and radiation hybrid mapping.

PMID- 14687082
TI  - Exclusion of PISRT1 as a candidate locus for canine Sry-negative XX sex reversal.

PMID- 14687083
TI  - Mapping of the porcine peroxisome proliferator activated receptor alpha gene to
      chromosome 5.

PMID- 14687084
TI  - Assignment of the porcine peptide YY gene to chromosome 12.

PMID- 14687085
TI  - Mapping of bovine CEBPD gene to BTA14q15-17.

PMID- 14687086
TI  - Assignment of the porcine stearoyl-CoA desaturase (SCD) gene to SSC14q27 by
      fluorescence in situ hybridization and by hybrid panel mapping.

PMID- 14687087
TI  - Sequencing, tissue distribution and physical mapping of the porcine homologue of
      cardiomyopathy associated 3 (CMYA3).

PMID- 14687088
TI  - Mapping of the goat stearoyl coenzyme A desaturase gene to chromosome 26.

PMID- 14687089
TI  - The chicken bone morphogenetic protein receptor type II (BMPR2) gene maps to
      chromosome 7.

PMID- 14687090
TI  - The syringe is mightier than the pen.

PMID- 14687091
TI  - Therapeutic impact of intra-operative transoesophageal echocardiography during
      noncardiac surgery.
AB  - The impact of transoesophageal echocardiography on haemodynamic management during
      elective noncardiac surgery was assessed during this observational prospective
      database analysis. Ninety-nine consecutive patients were studied, who were at
      risk of intra-operative myocardial ischaemia or haemodynamic instability (Class
      II indications) and were undergoing vascular, visceral or chest surgery. A total
      of 165 new echocardiographic findings were recorded. Based on these findings
      changes in drug therapy were made in 47% and changes in fluid therapy in 24% of
      patients. Left ventricular wall motion abnormalities were seen in 32% and other
      relevant diagnoses made in 10%. Echocardiography showed a significant impact on
      drug therapy in patients with pre-operative systolic wall motion abnormalities
      (vasodilators: OR = 7.1, CI 95% = 2.1/24.0; vasopressors: OR = 3.3, CI 95% =
      1.2/9.1) and patients with a history of left heart failure (vasodilators: OR =
      5.2, CI 95% = 1.0/31.4). Fluid therapy was significantly influenced by
      echocardiographic findings during liver and lung transplantation (50% compared
      with 24% during other surgical interventions, p < 0.05).

PMID- 14687092
TI  - The effect of nitrous oxide on cerebral blood flow velocity in children
      anaesthetised with sevoflurane.
AB  - To determine the effects of nitrous oxide on middle cerebral artery blood flow
      velocity (CBFV) during sevoflurane anaesthesia in children, CBFV was measured
      using transcranial Doppler sonography in 16 ASA I or II children. Anaesthesia
      consisted of 1.0 MAC sevoflurane in 30% oxygen with intermittent positive
      pressure ventilation maintaining FEco2 at 38 mmHg (5.0 kPa) and a caudal epidural
      block using 0.25% bupivacaine 1.0 ml.kg-1. The remainder of the inspired gas was
      varied in one of two sequences either air/nitrous oxide/air or nitrous
      oxide/air/nitrous oxide. The results showed that CBFV decreased when nitrous
      oxide was replaced by air (p = 0.03) and returned to its initial value when
      nitrous oxide was reintroduced. CBFV increased when air was replaced by nitrous
      oxide (p = 0.04) and returned to its initial value when air was reintroduced.
      Mean heart rate and blood pressure remained constant. We conclude that nitrous
      oxide increases cerebral blood flow velocity in healthy children anaesthetised
      with 1.0 MAC sevoflurane.

PMID- 14687093
TI  - A comparison of 8% and 12% sevoflurane for inhalation induction in adults.
AB  - Sevoflurane is a non-pungent volatile anaesthetic agent with a low blood-gas
      solubility coefficient. It has been studied in concentrations of up to 8% for
      induction of anaesthesia. Previous work has suggested that there may be a ceiling
      effect with increasing concentration of sevoflurane above 6%, but there are no
      published studies using 12% sevoflurane. This study compared 8 and 12%
      sevoflurane to induce anaesthesia in adults. Sevoflurane was administered using
      two adapted datum vaporisers with the interlock removed. Induction with 12%
      sevoflurane compared to 8% sevoflurane produced a significant decrease in the
      time to achieve central pupils, corresponding to surgical anaesthesia and the
      third part of Guedel's stage 3 of anaesthesia (mean time (SD) 201 s (81) and 247
      s (39), respectively, p < 0.05). Twelve-percent sevoflurane produced a similar
      stable cardiovascular profile to 8% sevoflurane, and there was no increase in
      respiratory complications.

PMID- 14687094
TI  - A pilot study of evaluation of cerebral function by S100beta protein and near
      infrared spectroscopy during cold and warm cardiopulmonary bypass in infants and
      children undergoing open-heart surgery.
AB  - Cerebral injury in children undergoing cardiopulmonary bypass (CPB) remains a
      major source of morbidity. The effect of cardiopulmonary bypass temperature on
      cerebral function in terms of serum S100beta protein level and cerebral
      oxygenation monitored by near infrared spectroscopy (NIRO-300) in children is not
      known. In this study, 18 children undergoing open-heart surgery at the Hospital
      for Sick Children in London were equally assigned by minimisation to warm (35 +/-
      1 degrees C) or cold (25 +/- 1 degrees C) CPB. Changes in S100beta protein and
      cerebral oxygenation were studied in both groups. S100beta protein serum level
      increased significantly after CPB in both groups. There was no significant
      difference in serum S100beta protein concentrations between the two groups.
      However, cerebral oxygenation in terms of tissue oxygen index (TOI) was
      significantly impaired during rewarming from cold CPB. Five patients were
      desaturated (TOI < 50%) during rewarming in the cold bypass group compared to two
      in the warm patients. This study supports the use of warm CPB in children
      undergoing open-heart surgery, although further studies recruiting more patients
      are warranted.

PMID- 14687095
TI  - Assessment of tracheal intubation in children after induction with propofol and
      different doses of remifentanil.
AB  - Tracheal intubating conditions were assessed in 112 children after induction of
      anaesthesia with propofol and remifentanil 1.0, 2.0 or 3.0 micro g.kg-1. Subjects
      in a control group were given propofol and mivacurium 0.2 mg.kg-1. Haemodynamic
      and respiratory parameters were recorded. Plasma catecholamine levels were
      measured in a subgroup of 40 children. Intubating conditions were acceptable in
      14/28 (50%), 18/26 (69%) and 22/27 (82%) in those subjects given remifentanil
      1.0, 2.0 or 3.0 micro g.kg-1, respectively, and in 27/28 (96%) of the control
      group. Intubating conditions in subjects given remifentanil 3.0 micro g.kg-1 were
      better than in those given remifentanil 1.0 micro g.kg-1 (p < 0.05). There were
      no significant differences in intubating conditions between those given
      remifentanil 3.0 micro g.kg-1 and the control group. Systolic blood pressure and
      heart rate increased in response to tracheal intubation in subjects given
      remifentanil 1.0 micro g.kg-1 and in the control group (p < 0.05). Time to
      resumption of spontaneous respiration was prolonged in subjects given
      remifentanil 3.0 micro g.kg-1 (p < 0.001). In conclusion, remifentanil 2 micro
      g.kg-1 provides acceptable intubating conditions and haemodynamic stability
      without prolonging the return of spontaneous respiration.

PMID- 14687096
TI  - Simple bedside assessment of level of consciousness: comparison of two simple
      assessment scales with the Glasgow Coma scale.
AB  - Neurological assessment is an essential component of early warning scores used to
      identify seriously ill ward patients. We investigated how two simple scales (ACDU
      - Alert, Confused, Drowsy, Unresponsive; and AVPU - Alert, responds to Voice,
      responds to Pain, Unresponsive) compared to each other and also to the more
      complicated Glasgow Coma Scale (GCS). Neurosurgical nurses recorded patients'
      conscious level with each of the three scales. Over 7 months, 1020 analysable
      measurements were collected. Both simple scales identified distinct GCS ranges,
      although some overlap occurred (p < 0.001). Median GCS scores associated with
      AVPU were 15, 13, 8 and 6 and for ACDU were 15, 13, 10 and 6. The median values
      of ACDU were more evenly distributed than AVPU and may therefore be better at
      identifying early deteriorations in conscious level when they occur in critically
      ill ward patients.

PMID- 14687097
TI  - Bougie-assisted difficult airway management in a manikin - the effect of position
      held on placement and force exerted by the tip.
AB  - In a randomised cross-over study, 50 anaesthetists attempted to place a multiple
      use bougie in the trachea of a manikin, when holding it at either 20 cm or 30 cm
      from the tip. A grade 3 laryngoscopic view was simulated. The anaesthetists were
      blinded to success (tracheal placement) or failure (oesophageal placement). The
      success rates when held at 20 and 30 cm distance from the tip were 68 and 62%,
      respectively (p = 0.55). In a separate experiment, multiple and single-use
      bougies were held at four different positions and pressed onto a disc attached to
      a force transducer. The peak force exerted by the single-use bougies was two to
      three times greater than that which could be exerted by the multiple-use bougies
      (p < 0.0001). Holding the bougie at either 20 or 30 cm distance from the tip is
      unlikely to influence bougie placement. The single-use bougie is much more likely
      to cause trauma to tissue during placement, particularly if held close to the
      tip.

PMID- 14687098
TI  - Anaesthetic management in facial bipartition surgery: the experience of one
      centre.
AB  - Facial bipartition is amongst the most radical craniofacial surgery undertaken
      but is performed rarely. There is little published information on its anaesthetic
      management. We undertook a retrospective case-note review of 22 consecutive
      patients undergoing bipartition surgery by the same surgical team in one centre
      in the period 1993-2001. There were incomplete data for two cases and these were
      therefore excluded. Patients were aged 2 months to 19 years. Conditions treated
      were facial cleft (n = 5), frontonasal dysplasia (n = 7) and facial dysostosis (n
      = 8).Intra-operative complications included major haemorrhage (n = 4),
      bradycardia (n = 3) and unintentional tracheal extubation (n = 1). There were no
      peri-operative deaths. All patients required intra-operative blood transfusion
      and 15% of them had a postoperative haemoglobin concentration > 115% of their pre
      operative value. In this series, four patients required postoperative lung
      ventilation for a median duration of 3 days. Infants < 14 months old were
      significantly more likely to receive a massive blood transfusion (p = 0.0002), to
      have an excessively high postoperative haematocrit (p = 0.008) and to require
      postoperative lung ventilation (p = 0.0002) compared with older patients. We
      conclude that patients in this age group have a significantly increased risk of
      postoperative complications.

PMID- 14687099
TI  - Entropy during propofol hypnosis, including an episode of wakefulness.
AB  - Depth of anaesthesia has proved to be a complex process to quantify. Monitors
      based on bispectral analysis of the electroencephalogram and auditory evoked
      potential have been available, but only recently has a monitor based on entropy
      become available. This study determined state entropy and response entropy in
      nine healthy volunteers during propofol hypnosis with a brief intervening period
      of wakefulness. Both the calculated entropy indices decreased with increasing
      levels of sedation (r2 = 0.58 and 0.61, respectively) and they showed a high
      correlation with each other (r2 = 0.94). However, an overlap was observed in real
      time indices between different stages of the Observer's Assessment of
      Alertness/Sedation Scale. Only three of the nine volunteers had explicit memories
      from the episode of wakefulness. Electroencephalographic entropy monitors seem to
      have potential for staging clinical hypnotic effects.

PMID- 14687100
TI  - Unplanned admission rates and postdischarge complications in patients over the
      age of 70 following day case surgery.
AB  - The elderly are a group of patients who would seem ideally suited to day surgery.
      However, age was initially regarded as a potential barrier to this process. We
      conducted a retrospective review of 1647 elderly patients (> 70 years of age)
      over a two-year period. Our results show a favourable outcome for these patients
      with low rates of unplanned admission and postoperative complications. Elderly
      patients seem to be at no increased risk of complications after day surgery, and
      show excellent satisfaction scores.

PMID- 14687101
TI  - Peri-operative beta-blockade and haemodynamic optimisation in patients with
      coronary artery disease and decreasing exercise capacity presenting for major
      noncardiac surgery.
AB  - Patients with coronary artery disease presenting for major noncardiac surgery may
      have indications for both peri-operative beta-blockade and haemodynamic
      optimisation. The combination of peri-operative cardiorespiratory failure and
      myocardial ischaemia has a grave prognosis. Recent investigations have shown that
      in patients with coronary artery disease, beta-blockade does not depress cardiac
      output as much as originally thought. There may, therefore, be a place for both
      peri-operative beta-blockade and haemodynamic optimisation. The indications for
      peri-operative beta-blockade and haemodynamic optimisation, the effect of acute
      beta-blockade on cardiac output in patients with coronary artery disease, and the
      interaction of peri-operative beta-blockade and haemodynamic optimisation are
      discussed.

PMID- 14687102
TI  - Problems with capnography at high altitude.
AB  - The aim of this study was to investigate why capnographs malfunction at high
      altitude, in order to suggest ways of improving instrument reliability. Four
      machines were decompressed to simulated high altitude and measurements taken. The
      study showed that the reduced air density at altitude has effects upon the pump,
      causing difficulty in entraining gas, and that high altitude has additional
      effects upon calibration of the instruments.

PMID- 14687103
TI  - Comparison of four different emergency airway access equipment sets on a human
      patient simulator.
AB  - This study used a patient simulator to study the ease of use and efficacy of four
      currently available cricothyroidotomy sets. We assessed the success of insertion
      of each piece of equipment and measured the subsequent adequacy of oxygenation
      and ventilation. We also examined the complications encountered using each set.
      We found that there was a 100% success rate of achieving an adequate airway
      within acceptable time limits using the 'Quiktrach' and 'Melker' sets, with good
      airway patency and ease of ventilation. There was an unacceptably high failure
      rate in achieving a patent airway when using the 'Transtracheal airway catheter
      with ENK-flow modulator' and 'Patil's airway'. The pre-assembled and user
      friendly 'Quiktrach' set provided the fastest and most effective means of
      oxygenation in the simulated patient requiring an emergency surgical airway.

PMID- 14687104
TI  - A prospective, randomised clinical evaluation of a new safety-orientated
      injectable drug administration system in comparison with conventional methods.
AB  - Fifteen anaesthetists were observed while providing anaesthesia for 15 pairs of
      adult cardiac surgical operations, using conventional methods for one of each
      pair and a new drug administration system designed to reduce error for the other.
      Aspects of each method were rated by users on 10-cm visual analogue scales (10
      being best). The new system was rated more favourably than conventional methods
      in terms of safety (median [range] = 8.1 [6.8-9.7] vs. 7.1 [2.6-9.3] cm; p =
      0.001) and usability (8.5 [5.9-9.4] vs. 7.5 [3.2-9.8] cm; p=0.027). The new
      system saved preparation time both before anaesthesia (median [range] = 180 [32
      480] vs. 360 [120-600] s; p=0.013) and during anaesthesia (10 [2-38] vs. 12 [10
      60] s; p=0.009). Prefilled syringes for the new system increased costs by euro
      23.00 per anaesthetic (p = 0.041), but this increase is likely to be offset by
      the potential of the new system to decrease costly iatrogenic harm by preventing
      drug error.

PMID- 14687105
TI  - Clinical governance in pain management.

PMID- 14687106
TI  - Fresh frozen plasma for succinylcholine apnoea.

PMID- 14687107
TI  - Training in airway management.

PMID- 14687108
TI  - Cricoid pressure.

PMID- 14687109
TI  - Images in clinical anaesthesia: extrathoracic post-traumatic lung herniation.

PMID- 14687110
TI  - Pain and intramuscular injections.

PMID- 14687111
TI  - Disposable laryngoscopes are not always inferior to non-disposable laryngoscopes.

PMID- 14687112
TI  - White cell count and intensive care unit outcome: rethinking the vocabulary.

PMID- 14687113
TI  - Peripartum anaesthetic management of a parturient with spinal cord injury and
      autonomic hyperreflexia.

PMID- 14687114
TI  - Caesarean section in a parturient with type III spinal muscular atrophy and pre
      eclampsia.

PMID- 14687115
TI  - Upper airway obstruction in a patient with a tracheostomy.

PMID- 14687116
TI  - Introductory day for new college tutors.

PMID- 14687117
TI  - An audit of an audit: local causes of inaccuracy in 'Who operates when II?'.

PMID- 14687118
TI  - Modified Magill's forceps revisited.

PMID- 14687119
TI  - Theoretical value of Hufner's constant.

PMID- 14687120
TI  - Confusion relating to drug syringe labels.

PMID- 14687121
TI  - Another foreign body in a laryngeal mask airway.

PMID- 14687131
TI  - Should the national GI fellowship matching program be restored? Pro:
      Gastroenterology match: good for all the players.

PMID- 14687132
TI  - Should the national GI fellowship matching program be restored? Con: The
      gastroenterology fellowship match: R.I.P.

PMID- 14687133
TI  - Should the national GI fellowship matching program be restored? Balancing view:
      The GI match: What is in the balance?

PMID- 14687134
TI  - The difficult colon polyp.

PMID- 14687135
TI  - Dilated intercellular spaces and shunt permeability in nonerosive acid-damaged
      esophageal epithelium.
AB  - OBJECTIVES: It has recently been established that patients with nonerosive reflux
      disease have on biopsy within esophageal epithelium a lesion known as dilated
      intercellular spaces (DIS). METHODS: To further explore the nature and
      implications of this lesion, in vitro models of nonerosive acid and acid-pepsin
      damage were created in Ussing chamber-mounted rabbit esophageal epithelium. Using
      these models circuit analysis and permeability studies were carried out, the
      latter using dextran of varying size and human epidermal growth factor (EGF).
      RESULTS: Luminal HCl, pH 1.1, or HCl, pH 2.0 + pepsin, 1 mg/ml, for 30 min
      significantly reduced transepithelial electrical resistance (RT) but produced no
      gross erosions or histologic evidence of cell necrosis. Transmission electron
      microscopy, however, documented the presence of DIS. Circuit analysis on healthy
      esophageal epithelium showed that shunt resistance (RS) was much lower than
      apical membrane, basolateral membrane and transcellular resistances (Ra, Rb, and
      Rcell, respectively) and approached that of RT. Further, circuit analysis on acid
      and acid-pepsin damaged tissues showed that the declines in RT resulted from
      declines in RS. Moreover, the declines in RT (and so RS) were associated with a
      linear increase in permeability to 4 kD dextrans as well as an increase in
      permeability to 6 kD EGF and dextrans as large as 20 kD. CONCLUSIONS: In
      nonerosive acid-damaged esophageal epithelium DIS develop in association with and
      as a marker of reduced transepithelial resistance and increased shunt
      permeability. This change in shunt permeability upon acid or acid-pepsin exposure
      is substantial, permitting dextran molecules as large as 20 kD (33 A) to diffuse
      across the epithelium. Also, this shunt leak enables luminal EGF at 6 kD to
      diffuse across the acid-damaged epithelium and by so doing enables it to access
      its receptors on epithelial basal cells. We hypothesize that the shunt leak of
      EGF may in part account for the development of a reparative phenomenon on
      esophageal biopsy in patients with nonerosive reflux disease known as basal cell
      hyperplasia.

PMID- 14687136
TI  - A 50-year analysis of 562 gastric carcinoids: small tumor or larger problem?
AB  - OBJECTIVES: Interest in gastric carcinoid tumors has amplified considerably given
      the biological establishment of their relationship to gastrin and advances in the
      elucidation of the pathobiology of such lesions. The recognized propensity of
      acid-suppressing agents such as the proton pump inhibitor class of drugs to
      increase plasma gastrin levels has been proposed as a causal relationship in the
      apparent increase in the identification of such lesions although the increased
      prevalence of endoscopy and the enhanced awareness of pathologists have also been
      considered as contributory factors. We sought to examine if there has been an
      increase in gastric carcinoid incidence time correlative with these parameters.
      METHODS: Carcinoid tumor cases from the End Results Group (1950-1969) and the
      Third National Cancer Survey (TNCS) (1969-1971) databases were combined with the
      most recent release of the National Cancer Institute's Surveillance,
      Epidemiology, and End Results (SEER) registry (1973-1999); these three datasets
      revealed 13715 carcinoid cases, of which 562 were gastric in origin. Age-adjusted
      analyses as well as population-based gender and race correction ratios were
      completed in conjunction with United States decennial census data. To allow a
      finer granularity in incidence trends, the SEER database was divided into early
      (1973-1991) and late (1991-1999) subsets. RESULTS Since 1950, the percentage of
      gastric carcinoids among all gastric malignancies has increased from 0.3% to
      1.77%. Since 1969, the proportion of gastric carcinoids among all enteric
      carcinoid lesions has increased from 2.4% to 8.7%. Age-adjusted incidence rates
      among male, female, black, and white population subsets have all increased since
      the TNCS time period, with the greatest increase (800%) noted in white females.
      The male:female ratio has fallen from 0.90 to 0.54. The occurrence of synchronous
      or metachronous noncarcinoid tumors with gastric carcinoid tumors has decreased
      by 26% during the course of SEER data collection. The 5-yr survival rate for
      gastric carcinoids overall has risen from 51% to 63% during the same time period.
      CONCLUSIONS: Gastric carcinoids have increased in incidence over the last 50 yr.
      Differential increases in predominance across gender and race subdivisions may
      reflect genetic-based propensities (or protection) for gastric carcinoid tumors
      among certain ethnic populations. Increased endoscopic surveillance and
      associated sophisticated pathological evaluation of gastric biopsies undoubtedly
      are responsible for some of the observed increase in the incidence of gastric
      carcinoid tumors. These data allow no specific role to be assigned to the effects
      of acid-suppressive medications. Nevertheless the role of such agents cannot be
      discounted at this time since the time frame of the increased incidence is
      somewhat comparable to the introduction of these agents as is the known
      biological effect of gastrin on ECL cell proliferation.

PMID- 14687137
TI  - Computer simulator training enhances the competency of gastroenterology fellows
      at colonoscopy: results of a pilot study.
AB  - OBJECTIVES: Computer-based colonoscopy simulation (CBCS) is being utilized in
      endoscopy training without supporting evidence that it improves patient-based
      colonoscopy performance. The goal of this pilot study was to determine if CBCS
      training improves gastroenterology (GI) fellows' patient-based colonoscopy
      skills. METHODS: Competency at colonoscopy among 4 novice GI fellows who
      completed a 6-h CBCS curriculum was compared with 4 novice fellows who were not
      CBCS-trained. Measurements of competency were rendered by supervising faculty by
      recording "insertion time,""depth of unassisted insertion,""independent procedure
      completion,""ability to identify endoscopic landmarks,""inserts in a safe
      manner,""adequately visualizes mucosa on withdrawal," and "responds appropriately
      to patient discomfort" with each colonoscopy. RESULTS: Simulator-trained fellows
      outperformed traditionally trained fellows during their initial 15 colonoscopies
      in all performance aspects except "insertion time" (pp < 0.05). Simulator-trained
      fellows inserted the endoscope significantly further and reached the cecum
      independently nearly twice as often during this early training period. Three
      parameters ("depth of insertion,""independent completion," and "ability to
      identify landmarks") demonstrated a continued advantage out to 30 colonoscopies.
      Beyond 30 procedures, there was no difference in the performance of the two
      groups. CONCLUSION: In this pilot study, a 6-h CBCS curriculum provides an early
      training advantage by enhancing competency at the early stages of patient-based
      colonoscopy. These advantages are negligible after approximately 30 patient-based
      procedures. CBCS-enhanced training may allow faculty to be more efficient with
      their colonoscopy practice.

PMID- 14687138
TI  - Can computer simulation accelerate the development of procedural competence?

PMID- 14687139
TI  - Endoscopic ultrasound is a sensitive and specific test to diagnose portal venous
      system thrombosis (PVST).
AB  - OBJECTIVES: Thrombosis of the portal venous system (PVS) may complicate
      cirrhosis, pancreatitis, malignancies, and hypercoagulable states. Computed
      tomography (CT) scanning can diagnose thrombi present in the lumen of the PVS,
      but is probably insensitive. Endoscopic ultrasound (EUS) may be a more sensitive
      test for diagnosing PVS thrombosis (PVST). We sought to determine the accuracy of
      EUS for the diagnosis of PVST. METHODS: Using a retrospective analysis of
      patients' studies retrieved from a database at Massachusetts General Hospital, we
      determined the sensitivity and specificity of EUS in 16 patients with PVST and 29
      without PVST as proven by surgery and/or CT scanning. All patients underwent a
      linear EUS exam of the PVS and the results of the EUS report were used as the
      basis of the study. RESULTS: The sensitivity of EUS for the finding of PVST was
      81% in 13 of 16 patients and the specificity was 93% in 27 of 29 patients with an
      overall accuracy of 89% (40/45). In an additional group of 11 patients, EUS
      demonstrated the presence of a PVST that was not detected by CT scanning.
      CONCLUSION: Linear EUS is a highly sensitive and specific test for PVST.

PMID- 14687140
TI  - EUS-guided fine-needle aspiration of suspected hilar cholangiocarcinoma in
      potentially operable patients with negative brush cytology.
AB  - BACKGROUND: Despite improvements of diagnostic modalities differentiation between
      benign and malignant hilar strictures remains a challenge. Hilar neoplasia
      requires preoperative tissue diagnosis to avoid risk of inappropriate extensive
      surgery. This is commonly attempted using various techniques at ERCP, which have
      variable sensitivity and accuracy. We used endosonography-guided fine-needle
      aspiration (EUS-FNA) for the preoperative diagnosis of hilar cholangiocarcinoma
      (HC). METHODS: Prospective evaluation of 44 patients (31 male, mean age: 59 yr)
      with strictures at the liver hilum were diagnosed by CT and/or ERCP. All were
      suspicious of HC but had inconclusive tissue diagnosis. They underwent EUS-FNA
      with linear echo endoscope and 22 gauge needles. RESULTS: Adequate material was
      obtained in 43 of 44 patients. Cytology revealed HC in 26 and other malignancies
      in 5 patients; 12 had benign results: sclerosing cholangitis (n = 4), primary
      sclerosing cholangitis (n = 4), inflammation (n = 3), sarcoid-like lesion (n =
      1). There were no significant differences in age, lesion size, or echo features
      among patients with adenocarcinomas, other malignancies, or benign lesions.
      Thirty-two patients underwent surgery, 2 had autopsy, 10 were followed up
      clinically. Four of the benign results were false negatives. No complications
      occurred. Accuracy, sensitivity, and specificity were 91%, 89%, and 100%,
      respectively. EUS and EUS-FNA changed preplanned surgical approach in 27 of 44
      patients. CONCLUSION: These results suggest that EUS-FNA is of value as a new,
      less-invasive approach for tissue diagnosis of hilar strictures of unknown cause.
      It was technically feasible without significant risks, when other diagnostic
      tests were inconclusive and was able to change preplanned management in about
      half of the patients.

PMID- 14687141
TI  - Technical performance of colonoscopy in patients sedated with nurse-administered
      propofol.
AB  - OBJECTIVES: Nurse-administered propofol has gained attention as a safe and
      effective means of sedation for patients undergoing endoscopic procedures.
      However, little is known about the effect of propofol on the technical
      performance of colonoscopy. METHODS: Three separate studies were conducted. In
      the first study, we reviewed procedure notes from consecutive colonoscopies
      performed by a single experienced endoscopist at our hospital endoscopy unit on
      patients sedated with either nurse-administered propofol (n = 162) or
      midazolam/narcotic (n = 164). In the second study, 100 eligible colonoscopy
      outpatients were randomized to receive either nurse-administered propofol (n =
      50) or midazolam/fentanyl (n = 50). In both studies, the measured parameters
      included visualization of the cecum, time required to reach the cecum,
      repositioning of the patient, and the application of abdominal counterpressure.
      In a third study, we reviewed the rate of cecal intubation and colonic
      perforation in the first 2357 patients in our unit receiving nurse-administered
      propofol. RESULTS: In the retrospective comparative study, there was no
      difference in the cecal intubation rate in those receiving propofol (99.4%)
      compared to those receiving midazolam/narcotic (97%; p= 0.1), and three of five
      failed cecal intubations in the latter group resulted from obstructing masses.
      Patients sedated with propofol were repositioned less frequently compared to
      those receiving midazolam/narcotic (3.7%vs 26.2%) (p < 0.0001). Abdominal
      pressure was employed in 9.9% of patients sedated with propofol compared to 19.5%
      (p= 0.01) of those given midazolam/narcotic. The mean time to reach the cecum was
      lower in the propofol group than in the midazolam/narcotic group (4.6 min vs 6.0
      min, p= 0.002). In the prospective randomized study, the endoscopist intubated
      the cecum in all 100 patients. Patients in the propofol group were repositioned
      less frequently than those in the midazolam/fentanyl group (2%vs 24%,
      respectively, p= 0.001). The number of cases requiring abdominal counterpressure
      was not significantly different between the propofol and midazolam/fentanyl
      groups (12%vs 24%, respectively, p= 0.1). The mean time to reach the cecum in the
      propofol group (3.2 min) was similar to that in the midazolam/fentanyl group (3.8
      min, p= 0.08). Among the first 2357 patients in our unit undergoing colonoscopy
      with nurse-administered propofol, the rate of complete colonoscopy was 99.2% and
      there were no perforations. CONCLUSION: Nurse-administered propofol sedation is
      safe and simplifies the technical performance of colonoscopy compared to
      midazolam/narcotic sedation.

PMID- 14687142
TI  - Clinical course of lamivudine monotherapy in patients with decompensated
      cirrhosis due to HBeAg negative chronic HBV infection.
AB  - OBJECTIVES: We have evaluated the efficacy of long-term lamivudine monotherapy in
      patients with decompensated HBeAg-negative/HBV-DNA positive cirrhosis. METHODS:
      We analyzed the clinical course and outcome of lamivudine treatment in 30
      consecutive cirrhotics and compared with 30 HBV untreated historical HBeAg
      negative controls matched for age and gender. RESULTS: Significant clinical
      improvement, defined as a reduction of at least two points in Child-Pugh score
      was observed in 23 of the 30 treated patients (76.6%) versus none of the 30
      patients in the control group (p < 0.0001) after a mean follow-up of 20.6 +/-
      12.1(+/-SD) months. There were 10 deaths in the treated group versus 24 in the
      control group (p= 0.07). Liver-related deaths occurred in five of the eight
      patients soon after the development of biochemical breakthrough. Patients with
      clinical improvement had better survival than patients with no improvement (p=
      0.04) or those who developed biochemical breakthrough due to YMDD mutants (p=
      0.001). CONCLUSIONS: Lamivudine significantly improves liver function in HBeAg
      negative decompensated cirrhosis. However, the development of the biochemical
      breakthrough due to YMDD mutants is associated with fatal outcome.

PMID- 14687143
TI  - Management of decompensated HBV cirrhosis: lamivudine and beyond.

PMID- 14687144
TI  - Expression of matrix metalloproteinase-2 and -9 and tissue inhibitor of
      metalloproteinase-1 and -2 in intraductal and nonintraductal growth type of
      cholangiocarcinoma.
AB  - BACKGROUND: The intraductal growth (IG) type of cholangiocarcinoma has a better
      prognosis than the mass forming (MF) and periductal infiltrating (PI) types.
      Matrix metalloproteinase (MMP)-2 and MMP-9, regulated by tissue inhibitor of
      metalloproteinases (TIMP)-2 and TIMP-1, respectively, play important roles in the
      degradation of the basement membrane during tumor invasion. Alteration in MMPs
      and TIMPs may regulate the gross morphology of cholangiocarcinoma. METHODS: MMP-2
      and MMP-9 were analyzed in 35 cholangiocarcinomas and 4 normal livers with fresh
      tissue using zymography and real-time reverse transcription-polymerase chain
      reaction (RT-PCR), and expressions of MMP-2, MMP-9, TIMP-1, and TIMP-2 were
      evaluated in 76 cholangiocarcinomas by immunohistochemistry. RESULTS: Activity of
      MMP-2 and its active form were detected in 80% and 57% of cholangiocarcinomas
      respectively. The total MMP-2, active 62 kDa MMP-2, and MMP-2 mRNA increased 5.4
      and 8.2 times, 4.4 and 10.9 times, and 2.9 and 5.8 times in the MF and PI types,
      respectively, compared to the IG type. The majority of MMP-9 was in the proform
      and active 82 kDa MMP-9 was detected in 9% of cholangiocarcinomas. MMP-9 revealed
      no significant difference in relation to the gross types. The balanced
      expressions of MMP-2/TIMP-2 and MMP-9/TIMP-1 were significantly decreased in the
      MF and PI types, compared to the IG type. In the normal and nonneoplastic livers,
      the expressions of MMP-2 and MMP-9 were very low without active forms.
      CONCLUSIONS: The activities of MMP-2 and loss of balanced expressions of MMP
      2/TIMP-2 and MMP-9/TIMP-1 are suggested as playing important roles in invasive
      growth related to the gross type of cholangiocarcinoma.

PMID- 14687145
TI  - Cognitive lifetime drinking history in nonalcoholic fatty liver disease: some
      cases may be alcohol related.
AB  - OBJECTIVES: We aimed to determine the prevalence of significant alcohol intake in
      previously diagnosed nonalcoholic fatty liver (NAFL) patients. METHODS: We
      measured current and total lifetime alcohol intake (TLAI) in biopsy-proven NAFL
      patients using the cognitive lifetime drinking history (CLDH), a computerized
      questionnaire. One nurse administered the CLDH without physician presence.
      Physicians took alcohol histories prior to any knowledge of this study. Advanced
      and nonadvanced fibrosis patients were tested. A single pathologist (ST) scored
      all biopsies (inflammation 0-6; fibrosis 0-4). RESULTS: Twenty-three patients (11
      men) were studied. Thirteen had bridging fibrosis or cirrhosis. [mean age: 52.3
      yr (range 28-69); mean body mass index (BMI): 37 kg/m2 (range 27-48.6)]. All but
      three had hyperlipidemia, diabetes, and/or hypertension. Mean TLAI was 60.2 kg
      (range 0.17-471.7), but three patients were above 100 kg (threshold for cirrhosis
      risk) at 305.5, 336.7, and 471.7. These three had inflammation/fibrosis scores of
      3/3, 3/0, and 5/2, respectively. Those with >100 kg tended to have higher serum
      AST and inflammation score. Prior physician-obtained alcohol history determined
      <or=20 g/day for all patients and did not mention TLAI in any. CLDH confirmed
      <or=20 g/day current alcohol intake in 21 of 23 patients, but intakes were 30.2
      g/day and 41.2 g/day in two. CONCLUSIONS: Some NAFL patients may have alcohol
      fatty liver disease instead. Routine physician interviews obtain less accurate
      alcohol histories compared to CLDH. The clinical significance of past alcohol
      intake and methods of measuring alcohol ingestion in fatty liver patients
      deserves further investigation.

PMID- 14687146
TI  - Clinical and radiological responses after infliximab treatment for perianal
      fistulizing Crohn's disease.
AB  - OBJECTIVES: Infliximab is an effective therapy for fistulizing Crohn's disease of
      the perineum. We sought to determine whether the clinical improvement after
      infliximab is associated with radiological closure of fistula tracts. METHODS:
      Clinical responses and radiological imaging studies by transperineal ultrasound
      were evaluated in 35 patients with Crohn's disease perianal fistulas after
      treatment with infliximab 5 mg/kg up to 48 wk. Paired comparison of baseline and
      follow-up imaging studies at 8 wk and at 56 wk or discontinuation were assessed
      by an imaging score of perianal fistula severity, based on the Parks criteria.
      Complete clinical fistula closure and radiological healing were primary outcome
      measures. RESULTS: At 8 wk, after two infusions of infliximab at 0 and 2 wk,
      clinical fistula closure occurred in 49% of patients. The radiological score at 8
      wk was higher for patients with clinical fistula closure than for patients with
      no clinical improvement (p= 0.023) and two patients showed complete radiological
      healing. At 56 wk, clinical fistula closure occurred in 46% patients. Clinical
      fistula scores correlated with radiological scores (R2= 0.52; p < 0.001) but were
      not associated with fistula complexity, number of fistulas, or number of
      collections at baseline imaging. The proportion of patients with marked
      radiological improvement increased from 14% at 8 wk to 43% at 56 wks (p= 0.015)
      and complete radiological healing occurred in 4 (11%) patients. CONCLUSIONS: For
      perianal fistulizing Crohn's disease, repeat dose infliximab improves clinical
      and radiological outcomes, although complete radiological healing occurs in a
      minority of patients.

PMID- 14687147
TI  - Imaging and therapy for perianal Crohn's disease: on the right track?

PMID- 14687148
TI  - Remission in patients with Crohn's disease is associated with improvement in
      employment and quality of life and a decrease in hospitalizations and surgeries.
AB  - OBJECTIVES: Hospitalization, surgery, work loss, and impaired quality of life
      contribute to the cost and burden of care for patients with Crohn's disease. We
      examined the impact of remission on patients' employment, quality of life, and
      hospitalization and surgery in a clinical trial to validate clinical remission,
      as defined by the Crohn's disease activity index (CDAI), as the key treatment
      goal in managing Crohn's disease. METHODS: ACCENT I evaluated the efficacy and
      safety of long-term dosing of infliximab compared to a single dose of infliximab
      in 573 patients with moderately-to-severely active Crohn's disease. At wk 54,
      employment status was compared between patients in CDAI remission and those not
      in CDAI remission, for those not employed at baseline. Physical component summary
      (PCS) and mental component summary (MCS) scores of the SF-36 questionnaire were
      also compared between these two groups. The numbers of Crohn's-related
      hospitalizations and surgeries were compared among four groups of patients who
      spent 0-25%, 25-50%, 50-75%, and 75-100% of time, respectively, in CDAI remission
      during the study. RESULTS: At baseline, patients had a severely impaired quality
      of life and a high unemployment rate (38.4%). Among the group of patients who
      were unemployed at baseline, 31% of those patients who achieved CDAI remission
      (CDAI < 150) at wk 54 were employed, compared to 16% who were not in CDAI
      remission at wk 54 (p < 0.05). PCS and MCS scores of patients in CDAI remission
      at wk 54 were significantly higher (p < 0.0001), indicating better mental and
      physical functioning, than those of patients not in CDAI remission at wk 54, and
      were similar to those of the general U.S. population. Hospitalization and surgery
      rates decreased as the percentage of time patients were in CDAI remission
      increased (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: CDAI remission is
      associated with reduced hospitalizations and surgeries, increased employment, and
      normalized quality of life. Sustained CDAI remission should be the key
      therapeutic goal in managing Crohn's disease.

PMID- 14687149
TI  - Venous thromboembolism in inflammatory bowel disease.
AB  - OBJECTIVES: Venous thromboembolism has been associated with inflammatory bowel
      disease (IBD). We sought to describe the clinical features, acquired and
      congenital risk factors, and outcomes of venous thromboembolism in IBD. METHODS:
      All patients with confirmed IBD and deep venous thrombosis (DVT) or pulmonary
      embolism (PE) at our institution between 1991 and 2000 were identified. Medical
      records were abstracted for clinical features, risk factors, treatment, and
      outcomes. RESULTS: Fifty-nine ulcerative colitis (UC) patients (68% males) and 39
      Crohn's disease (CD) patients (41% males) were identified. UC extent was
      pancolonic in 76%, and CD extent was ileocolonic in 56%, colonic in 23%, and
      ileal in 21%. Eighty percent of CD patients and 79% of UC patients had active
      disease. Thrombophilia was present in 33% of the 40 patients tested. Most
      patients (87%) had other risk factors for DVT/PE. Long-term treatment included
      warfarin alone (62%), warfarin and IVC filter (18%), and IVC filter alone (7%).
      Five CD patients (13%) had recurrent DVT/PE. Among the 16 UC patients who
      underwent proctocolectomy following DVT/PE, there were two recurrences (13%),
      similar to the three recurrences (10%) seen among the 29 patients who had intact
      colons. Mortality rate was 22% after a median follow-up of 1.8 yr. CONCLUSIONS:
      Venous thromboembolism is a serious complication of IBD that may lead to death.
      Thrombophilia evaluations have a relatively high diagnostic yield overall,
      although specific genetic abnormalities are individually uncommon. Other DVT/PE
      risk factors are usually present. Proctocolectomy is not protective of recurrent
      DVT/PE.

PMID- 14687150
TI  - Magnetic resonance colonography in the detection of colonic neoplasm in high-risk
      and average-risk individuals.
AB  - OBJECTIVES: Magnetic resonance colonography (MRC) is a new noninvasive diagnostic
      modality for colorectal cancer. However, the use of MRC in the detection of
      colorectal neoplasm in average-risk individuals remains unknown. This study
      determined the performance and the patient's preference of MRC in the detection
      of colorectal neoplasm. METHODS: Both high-risk (i.e., symptoms suggestive of
      colorectal neoplasm, positive fecal occult blood test, history of colorectal
      cancer in one or more first-degree relatives) and average-risk (i.e.,
      asymptomatic individuals >50 yr) individuals were recruited. MRC was performed
      immediately prior to conventional colonoscopy (CC) by using air inflation without
      contrast. The finding on CC together with histology was used as a gold standard.
      Patients' pain and discomfort score were recorded immediately and 24 h after the
      procedure. They were also asked about their preferences for the two procedures.
      RESULTS: A total of 165 patients (79 average risk and 86 high risk) were
      recruited. Eight patients had incomplete MRC and one patient had failed CC. Of
      the remaining 156 patients, 4 were found to have colonic cancer and 31 were found
      to have 67 polyps. MRC correctly identified 3 cancers (sensitivity 75%,
      specificity 99.3%) and 4 patients with colonic polyps (sensitivity 12.9% and
      specificity 97.6%). Sensitivity of MRC tended to be lower in polyps <10 mm in
      size and in average-risk individuals. The mean procedure time of CC was
      significantly shorter than MRC (13.6 +/- 6.7 vs 20.6 +/- 2.7 min, p < 0.001).
      Although there was no significant difference in the pain and discomfort scores of
      the 2 procedures, 75% of patients preferred CC to MRC. CONCLUSIONS: The
      performance of MRC when used in the detection of colonic neoplasm in average-risk
      individuals is unsatisfactory.

PMID- 14687151
TI  - Accuracy of endoscopic ultrasound for restaging rectal cancer following
      neoadjuvant chemoradiation therapy.
AB  - OBJECTIVES: Endoscopic ultrasound (EUS) provides important information in the
      initial staging of patients with rectal cancer. Preoperative combined modality
      chemotherapy and radiation (neoadjuvant therapy) for patients with locally
      advanced rectal cancer may reduce local recurrence and improve survival. The
      accuracy of EUS restaging of rectal cancer after chemoradiation has not been
      extensively studied and its usefulness is unclear. The aim of this study was to
      verify the accuracy of EUS in staging rectal cancer after neoadjuvant
      chemoradiation in a large cohort of patients. METHODS: EUS staging was performed
      before and after concurrent 5-fluorouracil and hyperfractionated radiotherapy in
      82 patients with recently diagnosed locally advanced rectal cancer. All patients
      underwent subsequent surgical resection and complete pathologic staging. RESULTS:
      After chemoradiation, 16 patients (20%) had no residual disease at pathologic
      staging. (T0N0). However, EUS correctly predicted complete response to
      chemoradiation in only 10 of 16 patients (63%). Overall accuracy of EUS post
      chemoradiation for pathologic T-stage was only 48%. Fourteen percent were
      understaged and 38% overstaged. EUS accuracy for N-stage was 77%. The T-category
      was correctly staged before surgery in 23 of the 56 responders (41%) and in 16 of
      24 nonresponders (67%). EUS was unable to accurately distinguish postradiation
      changes from residual tumor. CONCLUSION: EUS staging of rectal cancer after
      chemoradiation is inaccurate, especially in the group of patients with visual and
      EUS evidence of response. Its routine use for staging purposes after neoadjuvant
      chemoradiation for rectal cancer should be discouraged.

PMID- 14687152
TI  - Clinical patterns over time in irritable bowel syndrome: symptom instability and
      severity variability.
AB  - OBJECTIVES: The clinical course of irritable bowel syndrome (IBS) remains poorly
      known. In 209 IBS patients meeting Rome II criteria (137 females and 72 males) we
      evaluated: (1). changes in frequency and intensity of abdominal pain/discomfort,
      abnormal number of bowel movements, loose or watery stools, defecatory urgency,
      hard or lumpy stools, straining during bowel movements, and feeling of incomplete
      evacuation); (2). use of resources, HRQoL, and psychological well being. METHODS:
      Observational, prospective, multicenter study. Symptoms were registered in a
      diary over two 28-day periods with an interval of 4 wk; direct resource use and
      indirect costs were noted weekly. Three HRQoL questionnaires were administered.
      RESULTS: High-intensity symptoms were present on more than 50% of the days. Sixty
      one percent were classified in the same IBS subtype on both occasions (kappa=
      0.48), while 49% had the same symptom predominance and intensity (kappa= 0.40).
      The greatest instability was observed among diarrhea (D-IBS) and constipation (C
      IBS) subtypes: only 46% and 51% remained in the same pattern with a tendency to
      shift to alternating diarrhea/constipation subtype (A-IBS); however, practically
      no patient changed from D-IBS to C-IBS, or vice versa. The most reliable symptom
      characteristic was frequency, followed by intensity and number of episodes.
      Symptom frequency and intensity were directly related to resource use and HRQoL
      impairment. CONCLUSIONS: IBS symptoms are instable over time and variables in
      intensity. Many patients with D-IBS or C-IBS move to A-IBS; however, shift from D
      IBS to C-IBS, or vice versa, is very infrequent.

PMID- 14687153
TI  - Splitting irritable bowel syndrome: from original Rome to Rome II criteria.
AB  - OBJECTIVES: Diagnosis of irritable bowel syndrome (IBS) and other functional
      bowel disorders (FBD) is based on symptom evaluation. Clinical criteria have
      changed over time, yielding different proportions of subjects fulfilling
      diagnostic requirements. According to new diagnostic criteria (Rome II), subjects
      considered some years ago to have IBS no longer do so. The aim of this article is
      to evaluate how patients diagnosed as having IBS according to original Rome
      criteria have been split, and to which clinical diagnosis they belong today.
      METHODS: Two hundred and eleven subjects meeting original Rome IBS diagnostic
      criteria were studied: 65 also met Rome II criteria while 146 did not. Subjects
      were extracted from an epidemiological survey, using home-based personal
      interviews, on 2000 subjects randomly selected as representative of the Spanish
      population. Clinical complaints, personal well-being, resource utilization, and
      health-related quality of life (HRQOL) were compared. RESULTS: Of the subjects
      meeting original Rome but not Rome II criteria, the present diagnosis should be:
      40%"minor" IBS (IBS symptoms of less than 12 wk duration), 37% functional
      constipation, 12% alternating bowel habit, 7% functional diarrhea, 3% functional
      abdominal bloating, and 1% unspecified functional bowel disorder (FBD). Thus, 52
      subjects (36%) should not be diagnosed with IBS because they really had other
      FBD, 59 (40%) because of symptoms consistent with IBD diagnosis but not the
      required duration or frequency, and 35 (24%) because of symptoms consistent with
      some other FBD diagnosis but not meeting the required duration. Clinical
      complaints, personal well-being, resource utilization, and HRQOL were more
      severely affected in IBS than in other FBD as a group, and in "major" rather than
      in "minor" forms. CONCLUSIONS: Many subjects meeting original Rome criteria for
      IBS do not meet Rome II criteria: approximately one quarter of subjects do not
      have sufficient symptom duration or frequency to be diagnosed with IBS and almost
      half are now considered as having other ("major" or "minor") FBD.

PMID- 14687154
TI  - Rectal function and bowel habit in irritable bowel syndrome.
AB  - OBJECTIVES: Rectal compliance may influence rectal perception, but their
      functional implications remain incompletely understood. Our aim was to determine
      whether rectal function is related to bowel habit in the irritable bowel
      syndrome. METHODS: The responses to fixed tension rectal distension applied by
      means of a tensostat were compared among constipation-predominant (n = 9),
      diarrhea-predominant (n = 7), alternating habit (n = 11) irritable syndrome
      subgroups, and healthy controls (n = 15). RESULTS: Overall, patients had normal
      rectal compliance and increased perception, but compliance was lower in diarrhea
      predominant as compared to constipation-predominant patients (6.7 +/- 0.7 ml/mmHg
      vs. 9.9 +/- 0.7 ml/mmHg, respectively; p < 0.05) and perception was higher (39 +/
      6 g vs. 64 +/- 9 g tolerance, respectively; p < 0.05). CONCLUSION: Distinctive
      tensosensitivity and compliance characterize rectal function in irritable bowel
      syndrome subgroups with different bowel habit.

PMID- 14687155
TI  - Factors associated with health-related quality of life in chronic pancreatitis.
AB  - OBJECTIVES: Chronic pancreatitis may lead to considerable reduction in health
      related quality of life, but factors associated with a poor perceived health
      status have not been investigated. METHODS: We recruited 265 patients with
      chronic pancreatitis from a tertiary care gastroenterology clinic. Health-related
      quality of life was assessed using the Short Form-36 Health Survey. Data were
      compared with age- and gender-adjusted values from the German general population
      (6964 adults). Factors associated with poor perceived health status were
      identified by logistic regression. RESULTS: All domains of health-related quality
      of life were reduced in chronic pancreatitis. Decrements were most pronounced in
      role limitations caused by physical (-25%) and emotional health problems (-15%),
      and general health perceptions (-19%). Severity of abdominal pain, chronic
      pancreatic diarrhea, low body weight, and loss of work independently contributed
      to the physical component score of the Short Form-36 (adjusted R2= 33.8%) and
      were the factors most closely associated with poor health status perception. The
      etiology and duration of the disease or changes in pancreatic morphology had no
      impact on health-related quality of life. CONCLUSIONS: Patients with chronic
      pancreatitis experience substantial impairments in health-related quality of
      life. The severity of chronic pancreatitis-related symptoms is directly
      associated with patient function and well-being. These data offer further insight
      into the impact of chronic pancreatitis on patient health status and may serve as
      the basis for the development of disease-specific instruments, which are needed
      to measure the effect of therapeutic interventions on patient-derived health
      outcomes.

PMID- 14687156
TI  - Timing of cholecystectomy for acute calculous cholecystitis: a meta-analysis.
AB  - OBJECTIVES: To compare early with delayed cholecystectomy for the treatment of
      acute lithiasic cholecystitis: a meta-analysis of prospective randomized trials.
      METHODS: Pertinent studies were selected from the Medline, Embase, Cancerlit,
      HealthSTAR and Cochrane Library Databases, references from published articles,
      and reviews. Twelve prospective randomized trials (9 addressing open
      cholecystectomy and 3 laparoscopic cholecystectomy) were selected. Conventional
      meta-analysis according to the DerSimonian and Laird method was used for the
      pooling of the results. The rate difference (RD) (95% CI) and the number needed
      to treat (NNT) were used as a measure of the therapeutic effect. RESULTS:
      Cumulative operative and perioperative mortality and morbidity were 0.9% and
      17.8%, respectively, for open cholecystectomy and 0% and 13.1%, respectively, for
      laparoscopic cholecystectomy. The pooled RD for operative complications in early
      surgery was 1.37% (95% CI =-3.78% to 6.53%; p= 0.2) for open cholecystectomy and
      3.11% (95% CI =-15.10% to 8.87%; p= 0.6) for laparoscopic cholecystectomy. In
      laparoscopic cholecystectomy the cumulative conversion rate to open
      cholecystectomy was 21.5%. The pooled RD for conversion rate in early
      laparoscopic cholecystectomy was -7.99% (95% CI =-18.46% to 2.47%; p= 0.1; NNT =
      13). Total hospital stay (mean +/- SD) was significantly shorter in the early
      surgery group (9.6 +/- 2.5 days vs 17.8 +/- 5.8 days; p < 0.0001). More than 20%
      of patients referred to delayed surgery fail to respond to conservative
      management or suffer recurrent cholecystitis in the interval period. CONCLUSIONS:
      Early operation (open or laparoscopic) does not carry a higher risk of mortality
      and morbidity compared to delayed operation and should be the preferred surgical
      approach for patients with acute lithiasic cholecystitis.

PMID- 14687157
TI  - Early versus delayed management for acute calculous cholecystitis: when should
      cholecystectomy be performed?

PMID- 14687158
TI  - Crohn's disease recurrence in a small bowel transplant.
AB  - This is a report of a patient with short-bowel syndrome secondary to recurrent
      surgeries for Crohn's disease who ultimately required small bowel transplantation
      in 1994. Eight years posttransplantation he developed recurrent Crohn's disease
      that was responsive to prednisone. From the perspective of advancing our
      understanding of Crohn's disease pathogenesis this case suggests that intestine
      specific antigens may be more important than the classical MHC antigens for the
      development of Crohn's disease, since this man developed Crohn's disease in both
      the native intestine and also in the engrafted one.

PMID- 14687159
TI  - Decision analysis in clinical gastroenterology.
AB  - OBJECTIVES: Although the tools of medical decision analysis have been mostly used
      to address complex issues of healthcare and management policies, an important
      role remains for decision analysis to play in solving mundane medical problems of
      daily practice. The present article aims to restate the origins of decision
      analysis and to demonstrate the utility of decision models in clinical
      gastroenterology. METHODS: Three clinical scenarios are presented to illustrate
      the applicability of decision analysis in clinical gastroenterology. The examples
      are modeled as simple decision trees and phrased in terms of threshold analysis.
      RESULTS: In spite of its striking simplicity, the framework of threshold analysis
      is able to capture a large variety of heterogeneous and often perplexing medical
      problems. Rather than calculate a cost-effectiveness or cost-benefit ratio, the
      result of the analysis is expressed as a probability value, which forms the
      threshold between the two choices against or in favor of a particular medical
      action. For most analyses little if any calculation is needed to solve the
      decision tree, and the final outcome of the analysis can be derived based on
      comparative estimates and considerations of magnitude only. CONCLUSIONS: The
      study demonstrates that threshold analysis can serve as a simple and convenient
      instrument to solve a large variety of problems in clinical gastroenterology.

PMID- 14687160
TI  - Diet, food intake, and disturbed physiology in the pathogenesis of symptoms in
      functional dyspepsia.
AB  - Functional dyspepsia (FD) remains a relatively poorly characterized
      gastrointestinal disorder of unknown etiology that is frequently difficult to
      manage. A systematic review of the literature relating to food intake and FD is
      summarized here. Many patients with FD report symptoms after meal ingestion,
      including fullness, bloating, epigastric pain, nausea, and vomiting, and this has
      been interpreted as indicative of an underlying "motor disorder of the stomach or
      small intestine." Such hypotheses are, however, still largely unsubstantiated,
      and the data that do exist are inconclusive, particularly as few studies have
      directly examined the temporal relationships between dyspeptic symptoms, meal
      ingestion, and disordered gastric motility. Moreover, studies attempting to
      relate symptoms to specific disturbances in gastric motor function have, in most
      cases, not evaluated symptoms concurrently with the function test, and/or have
      used suboptimal symptom scoring to quantify symptoms. Furthermore, the term
      "early satiety" has been used loosely as a symptom, rather than a quantitative
      measure of food intake. Currently, the most widely accepted mechanism underlying
      FD is visceral hypersensitivity, which may contribute to both enhanced motor and
      symptomatic responses to food ingestion. However, the possible contribution of
      food and dietary habits to the induction and/or exacerbation of dyspeptic
      symptoms represents a relatively new area-despite frequent reports by patients
      that their symptoms are often related to food ingestion; this association has not
      been formally assessed. Dietary assessments have frequently implicated fatty
      foods in symptom induction, and these findings are supported by laboratory-based
      studies, particularly the demonstration that FD patients more often experience
      symptoms after intraduodenal infusions of fat, than glucose. Further studies into
      the potential role of dietary factors in the induction of dyspeptic symptom are
      required to establish whether dietary therapies have any place in the management
      of FD.

PMID- 14687161
TI  - Predictors of early recurrence of benign esophageal strictures: what about
      eosinophilic esophagitis?

PMID- 14687163
TI  - Review article: chemoprevention of colorectal cancer.
AB  - Colorectal cancer is a disease with a high mortality at present, due to the late
      stage at which many cases present. Attention is therefore focusing on
      preventative strategies for colorectal cancer given that polyps appear to be
      identifiable and treatable precursor lesions of this disease. Endoscopic
      polypectomy has been shown to reduce the incidence of colorectal cancer and there
      is a good case for endoscopic screening of the general population. However, this
      will require a large amount of manpower and resources and its success will also
      depend on the overall compliance of the population. Epidemiological studies have
      shown that individuals reporting a regular intake of aspirin and other non
      steroidal anti-inflammatory drugs have a reduced risk of developing colorectal
      polyps and cancer. Similarly, a number of natural substances, such as calcium and
      folate, when supplemented regularly in the diet, have also been linked to a
      possible decreased incidence of colorectal cancer. This has led to the concept of
      using such agents to reduce the number of cases of colorectal cancer. In this
      article, we review the current evidence for the use of these and other agents for
      the chemoprevention of colorectal cancer, together with theories as to their
      possible mechanisms of action.

PMID- 14687164
TI  - Review article: current management of chronic hepatitis B.
AB  - Chronic hepatitis B can be diagnosed in patients with increased
      aminotransferases, hepatitis B virus viraemia and necroinflammation with fibrosis
      on liver biopsy. Although, ideally, all patients with chronic hepatitis B should
      be treated, therapeutic intervention is currently recommended for cases with a
      relatively satisfactory likelihood of response and/or advanced disease. A
      realistic therapeutic approach aims to sustain hepatitis B e antigen (HBeAg) loss
      and hepatitis B e antibody (anti-HBe) seroconversion in HBeAg-positive chronic
      hepatitis B and to sustain biochemical and virological remission in HBeAg
      negative chronic hepatitis B. Currently, three drugs are licensed for chronic
      hepatitis B: interferon-alpha, lamivudine and adefovir dipivoxil. In patients
      with HBeAg-positive chronic hepatitis B, all of these drugs achieve HBeAg loss
      (24-33%) and anti-HBe seroconversion (12-30%) rates significantly superior to
      those observed in untreated placebo controls. In patients with HBeAg-negative
      chronic hepatitis B, the sustained off-therapy response rate is 20-25% after a >
      or =12-month course of interferon-alpha and minimal (<10%), if any, after a 12
      month course of lamivudine or adefovir. Long-term lamivudine induces an initial
      response in 70-90% of patients, but only 30-40% of patients remain in remission
      after the third year due to progressively increasing viral resistance. Long-term
      adefovir achieves a response in approximately 70% of patients at 12 months, which
      is maintained at 24 months with rare (<2%) drug resistance. Adefovir is also
      effective against lamivudine-resistant strains. Many other anti-viral agents,
      immunomodulatory approaches and combination therapies are currently being
      evaluated in chronic hepatitis B.

PMID- 14687165
TI  - Review article: the ageing bowel and intolerance to aspirin.
AB  - Aspirin has a role in the prevention of cardiovascular and cerebrovascular
      disease, Alzheimer's dementia and several cancers. Encouraging all 50 year olds
      to take low-dose aspirin doubles their chances of living a healthy life into
      their nineties. The widespread use of aspirin, however, is limited as many older
      subjects are currently unable to take aspirin because of gastrointestinal side
      effects. This review explores why gastrointestinal events occur with aspirin use
      and how a net benefit from prophylactic aspirin might be achieved in older
      subjects. It is suggested that, by understanding the age-related changes in upper
      gastrointestinal physiology and the mechanisms by which aspirin leads to the risk
      reductions associated with its use, it may be possible to direct interventions to
      improve tolerability in older subjects. This would allow greater numbers of older
      subjects to gain the benefits associated with aspirin use.

PMID- 14687166
TI  - Glucocorticoid receptor expression in inflammatory bowel disease: evidence for a
      mucosal down-regulation in steroid-unresponsive ulcerative colitis.
AB  - BACKGROUND: Glucocorticoids (GC) play a major role in the attenuation of
      inflammation. Glucocorticoid receptor (GR) expression is an important determinant
      of steroid sensitivity. AIMS: To investigate whether GR mRNA expression is
      altered in inflammatory bowel disease, and whether GR mRNA expression correlates
      with disease activity and may predict response to GC therapy. METHODS: Mucosal
      biopsies were taken from 33 patients with ulcerative colitis, 21 with Crohn's
      disease and 11 controls. Peripheral blood mononuclear cells were isolated from 24
      ulcerative colitis and 18 Crohn's disease patients and 11 controls. GR mRNA was
      measured by quantitative reverse transcriptase polymerase chain reaction (RT
      PCR), and correlated to endoscopic findings, clinical activity and outcome of GC
      therapy. In a subset of subjects GR localisation was shown by
      immunohistochemistry. RESULTS: In patients with inflammatory bowel disease GR
      expression was not different from controls. However, GR was decreased in biopsies
      from ulcerative colitis patients with impaired GC response. The inhibitory
      subtype GRbeta was expressed 100-1000 times lower than GRalpha. GR
      immunoreactivity was identified in immune and epithelial cells except for colonic
      crypts. CONCLUSION: In inflammatory bowel disease systemic and mucosal GR mRNA
      expression is not altered. However, in ulcerative colitis patients, low mucosal
      GR expression may predict the outcome of GC therapy. The low expression of GRbeta
      challenges its role in steroid refractoriness in inflammatory bowel disease.

PMID- 14687167
TI  - Inflammatory bowel disease and hospital treatment in Italy: the RING multi-centre
      study.
AB  - AIM: To explore the management of chronic inflammatory bowel disease,
      specifically Crohn's disease and ulcerative colitis, in Italian gastroenterology
      units. METHODS: The RING (Ricerca Informatizzata in Gastroenterologia) project is
      an observational study collecting hospital discharge forms from 56 centres.
      Factors associated with the length of hospital stay were studied using
      multivariate logistic regression. RESULTS: In 24 months starting from August
      2000, out of 29,376 hospital discharge forms, 2131 (7.3%) were collected for
      inflammatory bowel disease (1163 for Crohn's disease and 968 for ulcerative
      colitis). The Crohn's disease and ulcerative colitis groups were compared
      according to demographic characteristics, diagnoses, procedures and hospital
      stay. In Crohn's disease, computed tomography/magnetic resonance imaging, x
      rays/barium enema, number of procedures and number of diagnoses were
      significantly associated with a hospital stay longer than 10 days. In ulcerative
      colitis, this association was found for parenteral nutrition, malnutrition,
      computed tomography/magnetic resonance imaging and number of procedures.
      CONCLUSIONS: Crohn's disease was confirmed as a disabling disorder requiring more
      frequent hospital treatment than ulcerative colitis. For the latter, parenteral
      nutrition and malnutrition were related to a longer hospital stay. The number of
      procedures, especially abdominal computed tomography/magnetic resonance imaging,
      was a major item for both pathologies.

PMID- 14687168
TI  - A comparison of hepatitis C treatment and outcomes at academic, private and
      Veterans' Affairs treatment centres.
AB  - BACKGROUND: Currently, there is a lack of published data examining hepatitis C
      treatment practices in different care settings. AIM: To provide data describing
      treatment practices for patients with hepatitis C virus infection in actual
      clinical practice, and to examine clinical outcomes in patients treated with
      interferon alpha-2b/ribavirin combination therapy in academically affiliated
      centres, private treatment centres and Veterans' Affairs treatment centres.
      METHODS: This multi-centre, retrospective, cohort study of 231 patients examined
      hepatitis C virus treatment practices in patients receiving interferon alpha-2b
      from January 1997 to May 2001 and explored outcomes in academically affiliated,
      private and Veterans' Affairs centres. RESULTS: Differences in treatment practice
      and use of diagnostic procedures were found. Genotype testing was under-utilized
      in non-academic sites (academic centres, 79.2%; private centres, 33.7%; Veterans'
      Affairs centres, 35.9%; P<0.001). Liver biopsies were performed less often in
      private sites (academic centres, 95.8%; private centres, 80.0%; Veterans' Affairs
      centres, 92.2%; P<0.01). End-of-treatment viral response (academic centres,
      40.0%; private centres, 31.3%; Veterans' Affairs centres, 17.2%; P<0.05) was
      lower than that found in published trial data. Multivariate analysis revealed
      genotype 1 as the single significant predictor of treatment failure (P<0.01).
      CONCLUSIONS: Outside of the academic setting, there is significantly less
      diagnostic work-up performed prior to the initiation of hepatitis C virus
      therapy. This suggests a need for a standardization of care across treatment
      settings.

PMID- 14687169
TI  - A pilot study to investigate the use of oxpentifylline (pentoxifylline) and
      thalidomide in portal hypertension secondary to alcoholic cirrhosis.
AB  - BACKGROUND: Tumour necrosis factor-alpha is thought to be important in the
      pathogenesis of portal hypertension. Oxpentifylline (pentoxifylline) and
      thalidomide inhibit endotoxin-induced tumour necrosis factor-alpha production in
      vitro. AIMS: To assess the toxicity of oxpentifylline (pentoxifylline) and
      thalidomide in cirrhosis and their effect on the hepatic venous pressure gradient
      and tumour necrosis factor-alpha production. METHODS: In an open-label pilot
      study, 20 abstinent patients with stable alcoholic cirrhosis and oesophageal
      varices were recruited; 12 patients completed haemodynamic measurements before
      and after treatment with oxpentifylline (pentoxifylline) 1800 mg (n=6) or
      thalidomide 200 mg (n=6) daily for 2 weeks. Tumour necrosis factor-alpha
      production was assessed in ex vivo monocyte cultures stimulated with endotoxin.
      RESULTS: Thalidomide reduced the hepatic venous pressure gradient from 19.7 mmHg
      (9.3-23.5 mmHg) to 12.2 mmHg (4.7-19.5 mmHg) (P=0.03) without reducing the
      hepatic blood flow or altering systemic haemodynamic parameters. Thalidomide
      reduced ex vivo tumour necrosis factor-alpha production by approximately 50%.
      Oxpentifylline (pentoxifylline) had no significant effect on any of the
      parameters measured. Side-effects led to dose reduction or treatment withdrawal
      in 40% of patients. CONCLUSION: Thalidomide, but not oxpentifylline
      (pentoxifylline), reduces the hepatic venous pressure gradient in stable
      alcoholic cirrhotics, an effect that may be mediated by the inhibition of tumour
      necrosis factor-alpha production. The role of tumour necrosis factor-alpha
      inhibitory drugs in the therapy of portal hypertension should be investigated in
      a randomized controlled trial.

PMID- 14687170
TI  - Low-dose furazolidone in triple and quadruple regimens for Helicobacter pylori
      eradication.
AB  - BACKGROUND: Furazolidone-based regimens for the eradication of Helicobacter
      pylori are low cost and effective. Unfortunately, the usual dose of furazolidone
      is not tolerable in many patients. Lower doses of furazolidone are expected to
      cause fewer adverse effects. AIM: To investigate the efficacy of low-dose
      furazolidone in the eradication of H. pylori. METHODS: One hundred and fifty
      patients with duodenal ulcer and H. pylori infection were randomly assigned to
      one of three treatment groups: omeprazole 20 mg b.d., amoxicillin 1000 mg b.d.
      and furazolidone 100 mg b.d. for 14 days (OAF); omeprazole 20 mg b.d.,
      amoxicillin 1000 mg b.d., furazolidone 100 mg b.d. and bismuth subcitrate 240 mg
      b.d. for 14 days (OABF1); or omeprazole 20 mg b.d., amoxicillin 1000 mg b.d.,
      furazolidone 200 mg b.d. and bismuth subcitrate 240 mg b.d. for 14 days (OABF2).
      RESULTS: Of the 150 patients, 145 completed treatment. The intention-to-treat and
      per protocol eradication rates were 54% (27/50), 72% (36/50) and 92% (46/50) for
      the OAF, OABF1 and OABF2 groups, respectively. The OAF and OABF1 groups showed
      significantly lower eradication rates than the OABF2 group (P<0.001 and P<0.01,
      respectively). CONCLUSIONS: Triple and quadruple furazolidone-based H. pylori
      eradication regimens do not yield acceptable success rates when a low dose of
      furazolidone (100 mg b.d.) is used.

PMID- 14687171
TI  - Symptoms of gastro-oesophageal reflux: prevalence, severity, duration and
      associated factors in a Spanish population.
AB  - AIM: To measure the prevalence of gastro-oesophageal reflux symptoms and to
      identify associated factors in a representative sample of the Spanish population.
      METHODS: A telephone survey of 2500 subjects was performed using a validated
      questionnaire. The association of gastro-oesophageal reflux symptoms (defined as
      the presence of heartburn or acid regurgitation) and their clinical
      characteristics with potential risk factors was summarized using the odds ratios
      (OR) obtained by multiple logistic regression. RESULTS: The response rate was
      71.2%. The annual prevalence of gastro-oesophageal reflux symptoms was 31.6% [95%
      confidence interval (CI), 29.8-33.4] and the weekly prevalence was 9.8% (95% CI,
      8.6-10.9). Gastro-oesophageal reflux symptoms were associated with excess weight
      (OR, 1.53; 95% CI, 1.23-1.92), obesity (OR, 1.74; 95% CI, 1.30-2.32), the
      psychosomatic symptom score (OR, 2.98; 95% CI, 2.41-3.67) and the presence of
      gastro-oesophageal reflux symptoms in a direct family member (OR, 1.61; 95% CI,
      1.17-2.23). Gastro-oesophageal reflux symptoms of > or =10 years' duration were
      more frequent in obese subjects (OR, 1.92; 95% CI, 1.14-3.22) and those with a
      direct family member with gastro-oesophageal reflux symptoms (OR, 2.42; 95% CI,
      1.44-4.06). Factors associated with gastro-oesophageal reflux symptoms of < or =1
      year duration were a spouse with gastro-oesophageal reflux symptoms (OR, 2.33;
      95% CI, 1.39-3.9) and the consumption of 1-5 aspirins/week (OR, 1.70; 95% CI,
      1.01-2.86). CONCLUSIONS: The prevalence of frequent gastro-oesophageal reflux
      symptoms in Spain is lower than that observed in other Western populations. The
      psychosomatic symptom score is the factor most strongly associated with gastro
      oesophageal reflux symptoms. Long-term gastro-oesophageal reflux symptoms are
      associated with certain genetic factors (obesity, family history of gastro
      oesophageal reflux symptoms), whereas short-term gastro-oesophageal reflux
      symptoms are associated with factors of probable environmental nature.

PMID- 14687172
TI  - Atrophic gastritis as a cause of hyperhomocysteinaemia.
AB  - BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for
      atherosclerosis. It is often related to low levels of vitamin B12 and/or folate,
      enzymatic co-factors of methionine metabolism. Atrophic gastritis, often caused
      by Helicobacter pylori infection, may impair vitamin absorption. AIM: To assess
      whether the presence of atrophic gastritis is associated with
      hyperhomocysteinaemia via deficiency of its vitamin co-factors. METHODS: Thirty
      one patients with atrophic gastritis were recruited. The control group consisted
      of 28 patients with non-atrophic gastritis, matched with patients for sex, age
      and body mass index. The presence and degree of gastric atrophy were assessed by
      histology. H. pylori infection was assessed by histology/serology. Blood samples
      were collected for the measurement of homocysteine, vitamin B12 and folates.
      RESULTS: Multiple logistic regression analysis showed that atrophic gastritis
      (odds ratio, 5.3; 95% confidence interval, 1.23-25.26; chi2=5.2; P=0.01) and low
      vitamin B12 (odds ratio, 3.7; 95% confidence interval, 1.03-22.08; chi2=3.6;
      P<0.05) were both predictors of hyperhomocysteinaemia. None of the other
      variables considered in the analysis, including H. pylori status, showed a
      significant association with hyperhomocysteinaemia. CONCLUSIONS: The present
      study suggests that atrophic gastritis, rather than H. pylori infection per se,
      may be a contributing factor to hyperhomocysteinaemia, possibly via vitamin B12
      malabsorption.

PMID- 14687173
TI  - Rabeprazole 10 mg twice daily is superior to 20 mg once daily for night-time
      gastric acid suppression.
AB  - BACKGROUND: Insufficient acid suppression is one of the main causes of proton
      pump inhibitor-refractory gastro-oesophageal reflux disease. AIM: To achieve more
      potent and long-lasting acid suppression, different dosage regimens of
      rabeprazole were compared in relation to the CYP2C19 genotype status. METHODS: In
      a cross-over study, 18 healthy Helicobacter pylori-negative males (six homozygous
      extensive metabolizers, six heterozygous extensive metabolizers and six poor
      metabolizers) were given rabeprazole 10 mg once daily, 20 mg once daily or 10 mg
      twice daily, or water only (baseline data), for 7 days each. On day 7 of each
      regimen, 24-h intragastric pH-metry was performed. RESULTS: No significant
      differences were observed in median pH values and pH>4 holding time ratios
      between rabeprazole 10 mg once daily and 20 mg once daily. However, with
      rabeprazole 10 mg twice daily, these parameters were significantly higher than
      those with 20 mg once daily. The potency of acid suppression by rabeprazole was
      influenced by the CYP2C19 genotype status. The differences were somewhat
      significant but not large. The incidence of nocturnal acid breakthrough was
      lowest with rabeprazole 10 mg twice daily. CONCLUSIONS: Rabeprazole 10 mg twice
      daily, not 20 mg once daily, should be administered to achieve more potent and
      long-lasting acid suppression.

PMID- 14687174
TI  - Anti-hyperalgesic effect of octreotide in patients with irritable bowel syndrome.
AB  - BACKGROUND: Octreotide has been found to be beneficial in the treatment of
      chronic pain, although the mechanisms underlying its therapeutic effect are
      incompletely understood. AIMS: To assess the effect of octreotide on perceptual
      responses to rectal distension in irritable bowel syndrome patients and healthy
      controls at baseline and following the experimental induction of rectal
      hyperalgesia. METHODS: In study 1, rectal perception thresholds for discomfort
      were determined in seven irritable bowel syndrome patients and eight healthy
      controls on three separate days using a computer-controlled barostat. Subjects
      received saline, low-dose and high-dose octreotide in a random double-blind
      fashion. In study 2, perceptual responses to rectal distension were obtained in
      nine irritable bowel syndrome patients and seven controls before and after
      repetitive high-pressure mechanical sigmoid stimulation. RESULTS: Octreotide
      increased the discomfort thresholds in irritable bowel syndrome patients, but not
      in controls, without changing rectal compliance. Repetitive sigmoid stimulation
      resulted in decreased rectal discomfort thresholds in the patient group only. In
      irritable bowel syndrome patients, octreotide prevented the sensitizing effect of
      repetitive sigmoid stimulation on rectal discomfort thresholds. CONCLUSIONS:
      Octreotide effectively increased discomfort thresholds in irritable bowel
      syndrome patients, but not in controls, at baseline and during experimentally
      induced rectal hyperalgesia. These findings suggest that octreotide exerts
      primarily an anti-hyperalgesic rather than analgesic effect on visceral
      perception.

PMID- 14687175
TI  - Empirically derived symptom sub-groups correspond poorly with diagnostic criteria
      for functional dyspepsia and irritable bowel syndrome. A factor and cluster
      analysis of a patient sample.
AB  - AIM: To determine how clusters (groups) of patients with respect to symptoms
      compare with a clinical diagnosis in patients with irritable bowel syndrome and
      non-ulcer dyspepsia. METHODS: All patients who attended a gastroenterology
      practice at Nepean Hospital were included in the study. All patients received the
      previously validated Bowel Disease Questionnaire, and were independently assessed
      by the gastroenterologist. Factor analysis and a k-means cluster analysis were
      completed. RESULTS: The study population comprised 897 patients [320 males (36%)
      and 577 females (64%)]. Factor analysis identified nine symptom factors: (1)
      diarrhoea; (2) constipation; (3) dysmotility; (4) dyspepsia/reflux; (5)
      nausea/vomiting; (6) bowel; (7) meal-related pain; (8) weight loss; and (9)
      abdominal pain. A k-means cluster analysis identified seven distinct subject
      groups, which included an undifferentiated group: (1) diarrhoea; (2) meal-related
      pain; (3) abdominal pain; (4) faecal indicators; (5) nausea/vomiting/weight loss;
      and (6) constipation. The majority of irritable bowel syndrome patients fitted
      into two cluster groups [diarrhoea (25%) and constipation (20%)], whereas those
      with non-ulcer dyspepsia predominantly fitted into the undifferentiated cluster
      (34%) and the nausea/vomiting cluster (18%). CONCLUSION: This study supports the
      concept of symptom subgroups, including the subdivision of patients into
      diarrhoea- and constipation-predominant irritable bowel syndrome.

PMID- 14687176
TI  - Study design issues in irritable bowel syndrome.

PMID- 14687177
TI  - The reproducibility of 13CO2 measurement.

PMID- 14687178
TI  - Meta-analysis: the relationship between Helicobacter pylori infection and gastro
      oesophageal reflux disease.

PMID- 14687180
TI  - Scanning electron microscopic examination of third metacarpal/third metatarsal
      bone failure surfaces in thoroughbred racehorses with condylar fracture.
AB  - OBJECTIVE: To examine the fracture failure surfaces from Thoroughbred horses that
      had sustained a catastrophic condylar fracture. SAMPLE POPULATION: Bone specimens
      from the failure surface were obtained from 12 Thoroughbred racehorses with
      catastrophic injury and 2 non-racing horses with accidental long bone fracture.
      METHODS: Bone specimens from the failure surface of each fracture were incubated
      with gold microspheres to label microcracks before examination at x50 to x60,000
      using scanning electron microscopy. Microcracking at the failure surface was
      assessed using a visual analog scale. RESULTS: Branching arrays or clusters of
      microcracks were seen over a range of magnifications in adapted subchondral bone
      in the distal end of the MC3/MT3 bone from racing Thoroughbreds with a
      catastrophic displaced condylar fracture. In the palmar/plantar region,
      microcracking was associated with the formation of an array of macroscopic cracks
      in the condylar groove. A different pattern of microcracking was seen in
      specimens of bone from distal metaphyseal and diaphyseal MC3/MT3 failure surfaces
      from Thoroughbred racehorses with catastrophic fracture and non-racing horses
      with an accidental diaphyseal long bone fracture. Few microcracks were seen and
      typically did not form branching arrays. CONCLUSION: These data suggest that
      propagation of condylar fracture in Thoroughbred racehorses is initiated by the
      formation of nanoscale microcracks in adapted subchondral bone that form during
      exercise-induced bone adaptation. CLINICAL RELEVANCE: Accumulation and
      coalescence of branching microcracks into arrays or clusters appears to
      eventually lead to the development of macroscopic subchondral cracks in the
      condylar groove and initiation of a condylar fracture.

PMID- 14687181
TI  - Effect of petrolatum coating on the rate of occlusion of ameroid constrictors in
      the peritoneal cavity.
AB  - OBJECTIVE: To document rate of closure and degree of inflammation associated with
      petrolatum coated (PCA) and non-coated ameroid constrictors (NCA) in the
      peritoneal cavity. STUDY DESIGN: Experimental study. ANIMALS: 18 Sprague-Dawley
      rats. METHODS: Thirty-six ameroid constrictors (AC; 5 mm) were digitally scanned
      and luminal area measured. Rats were anesthetized, and 1 PCA and 1 NCA were
      inserted in the peritoneal cavity by median celiotomy. Rats were euthanatized at
      2 weeks (6 rats), 4 weeks (6), or 6 weeks (6) after surgery. AC were harvested,
      digitally scanned, and luminal area determined. Inflammation associated with the
      AC was subjectively graded (1-5). The effects of petrolatum coating on luminal
      area measurements and inflammatory score were statistically analyzed. RESULTS:
      Closure of AC occurred most rapidly during the first 2 weeks, but luminal area
      decreased only 32% at 6 weeks after implantation. There was no significant
      difference in rate of closure for PCA compared to NCA at 2, 4, or 6 weeks.
      Inflammation scores were not significantly different between PCA and NCA.
      CONCLUSIONS: Petrolatum coating did not slow the rate of closure of AC in the
      peritoneal cavity. CLINICAL RELEVANCE: The lack of closure of AC supports the
      conclusion that vascular attenuation is not dependent on luminal constriction
      alone. Petrolatum coating did not slow the rate of casein expansion and is
      unlikely to be clinically useful.

PMID- 14687182
TI  - Prognostic implications of the degree of shunt narrowing and of the portal vein
      diameter in dogs with congenital portosystemic shunts.
AB  - OBJECTIVE: To determine prognostic evaluation and correlation of the degree of
      narrowing and the diameter of the portal vein in dogs with a congenital
      portosystemic shunt (CPS). STUDY DESIGN: Longitudinal prospective study. ANIMALS:
      Ninety-seven dogs with CPS. METHODS: Shunt diameter was recorded before and after
      silk ligation to calculate degree of closure. Portal vein diameter was measured
      in 74 dogs. Short-term (30 days) and long-term (>1 year) outcome were evaluated.
      Dogs with clinical signs after 1 year were re-examined to assess the degree of
      portosystemic shunting and compared with matched operated dogs without clinical
      signs. Correlations between clinical outcome, degree of closure, and portal vein
      diameter were statistically analyzed. RESULTS: Short-term and long-term mortality
      were 27% and 2.9% respectively. Clinical recurrence occurred in 10% of dogs. The
      degree of closure was significantly associated with mortality, but not with
      clinical recurrence. A significant correlation was found between degree of
      closure and the diameter of the cranial part of the portal vein. Portal vein
      diameter was only significantly associated with mortality in extrahepatic CPS.
      Subclinical portosystemic shunting was confirmed in 3 of 10 dogs. CONCLUSION: The
      degree of shunt closure depended on portal development. Long-term outcome did not
      depend on the degree of closure or portal development at the time of surgery.
      This suggested that factors such as hepatic and portal regeneration after surgery
      may be important. CLINICAL RELEVANCE: Determination of factors that predict the
      outcome after surgical treatment of CPS in dogs is important to gain insight in
      treatment selection or new therapeutic options.

PMID- 14687183
TI  - Outcomes of cellophane banding for congenital portosystemic shunts in 106 dogs
      and 5 cats.
AB  - OBJECTIVE: To report outcomes after cellophane banding of single congenital
      portosystemic shunts in dogs and cats. STUDY DESIGN: Retrospective study of
      sequential cases. ANIMALS: One hundred and six dogs and five cats. METHODS:
      Medical records were reviewed for breed, sex, age at surgery, shunt anatomy,
      results of pre- and postoperative biochemical analysis, development of
      postligation neurologic dysfunction, portal hypertension or other serious
      complications, and the owners' perception of their animal's response to surgery.
      RESULTS: Ninety-five dogs and all 5 cats had extrahepatic shunts. Eleven dogs had
      intrahepatic shunts. Six dogs (5.5%) died as a result of surgery from portal
      hypertension (2 dogs), postligation neurologic dysfunction (2), splenic
      hemorrhage (1) and suspected narcotic overdose (1). Serious complications were
      more common in dogs with intrahepatic shunts than those with extrahepatic shunts
      (P=.002). Postligation neurologic dysfunction necessitated treatment in 10 dogs
      and 1 cat; 8 dogs and the cat survived. Clinical signs attributed to
      portosystemic shunting resolved or were substantially attenuated in all
      survivors. Postoperative serum bile acid concentrations or results of ammonia
      tolerance testing were available for 88 animals; 74 (84%) were normal and 14
      (16%) were abnormal. Multiple acquired shunts were documented in two animals.
      CONCLUSIONS: Cellophane banding is a safe and effective alternative to other
      methods of attenuation. CLINICAL RELEVANCE: Slow occlusion of portosystemic
      shunts using a variety of methods is being evaluated world wide. Cellophane
      banding is a relatively simple procedure with comparable safety and efficacy to
      previously reported techniques.

PMID- 14687184
TI  - A new dissection technique for approach to right-sided intrahepatic portosystemic
      shunts: anatomic study and use in three dogs.
AB  - OBJECTIVE: To determine the feasibility of indirect suture passage around the
      right portal vein for attenuation of right-sided intrahepatic portosystemic
      shunts (IHPSS). STUDY DESIGN: Anatomic study of cadavers and prospective
      evaluation of clinical cases. ANIMALS: Nine canine cadavers (median weight, 20.5
      kg) and 6 client-owned dogs suspected of having right-sided IHPSS. METHODS:
      Silicone casts of the caudal vena cava and pre- and intrahepatic portal veins
      were made in fresh canine cadavers. A suture was passed dorsal to the portal vein
      above and below its bifurcation and pulled laterally so that it surrounded the
      right portal vein. The number and size of portal and caudal vena cava branches
      that interfered with the suture passage were recorded. Intra- and postoperative
      complications were evaluated in 3 dogs with right-sided IHPSS and 3 dogs
      suspected of having right-sided IHPSS that had right portal vein dissection and
      occlusion using this technique. RESULTS: Suture passage and placement around the
      right portal vein were easily accomplished in all 9 specimens. A 1 mm branch from
      the dorsal surface of the right portal vein was included in the encircling
      ligature in 4 specimens. The dissection technique was used successfully in 3 dogs
      with right-sided IHPSS and 2 other clinical cases. The portal branch to the
      papillary process of the caudate lobe interfered with suture placement in 1 dog
      with a central IHPSS. CONCLUSIONS: Indirect suture passage for ligation of the
      right portal vein can be successfully performed in normal dogs and dogs with
      congenital portosystemic shunts. CLINICAL RELEVANCE: Hemorrhage, vascular trauma,
      and surgery time may be reduced using this technique for attenuation of right
      sided IHPSS.

PMID- 14687185
TI  - Effects of extracorporeal shock wave therapy on bone.
AB  - Extracorporeal shock waves have been used for 30 years to fragment uroliths for
      nonsurgical treatment for urolithiasis in humans. Applied to bone, shock waves
      delivered at the appropriate energy and pulse number, can stimulate osteogenesis.
      In Europe, shock waves are routinely used to treat nonunions in humans despite
      poor understanding of the mechanism of action. Shock wave therapy has also been
      used clinically in horses. Preliminary experimental studies indicate that shock
      wave therapy does not damage soft tissue in the distal aspect of the equine limb
      and can stimulate osteogenesis throughout the depth of the near cortex of the
      metacarpus and metatarsus.

PMID- 14687186
TI  - Effect of focused and radial extracorporeal shock wave therapy on equine bone
      microdamage.
AB  - OBJECTIVES: To determine whether bone microcracks are altered after application
      of focused and radial extracorporeal shock wave therapy (ESWT) to the equine
      distal limb. STUDY DESIGN: An ex vivo experimental model. SAMPLE POPULATION: A
      contralateral limb specimen was obtained from 11 Thoroughbred racehorses with a
      unilateral catastrophic injury. Distal limb specimens were also obtained from 5
      non-racing horses. METHODS: Three separate skin-covered bone segments were
      obtained from the mid-diaphysis of the metacarpus (MC3) or metatarsus (MT3).
      Focused (9,000 shockwaves, 0.15 mJ/mm2, 4 Hz) and radial (9,000 shockwaves, 0.175
      mJ/mm2, 4 Hz) ESWT treatments were randomized to the proximal and distal segments
      and the middle segment was used as a treatment control for pre-existing
      microcracks. After treatment, bone specimens were bulk-stained with basic fuchsin
      and microcracks were quantified in transverse calcified bone sections. RESULTS:
      ESWT had small but significant effects on microcracks. Microcrack density (Cr.Dn)
      and microcrack surface density (Cr.S.Dn) were increased after focused ESWT,
      whereas Cr.Le was increased after radial ESWT. In racing Thoroughbreds, Cr.Le
      increased with increased number of races undertaken. Cr.Dn and Cr.S.Dn were not
      significantly influenced by the number of races undertaken. CONCLUSION: ESWT has
      small but significant effects on bone microcracking ex vivo. CLINICAL RELEVANCE:
      These preliminary data suggest that ESWT has the potential to increase bone
      microcracking in equine distal limb bone in vivo. Such effects may be more
      pronounced in Thoroughbreds that are actively being raced, because in vivo
      microcracking increases with increased number of races undertaken.

PMID- 14687187
TI  - Laser lithotripsy for treatment of canine uroliths.
AB  - OBJECTIVE: To confirm in vivo optimal laser energy settings previously determined
      in vitro for lithotripsy, to develop a technique for Ho:YAG laser lithotripsy,
      and to evaluate acute and chronic tissue effects of laser lithotripsy. STUDY
      DESIGN: Prospective, randomized preclinical trial. ANIMALS OR SAMPLE POPULATION:
      Nineteen intact, adult male dogs. METHODS: Via cystotomy, a single urolith was
      inserted into the urethra to the level of the base of the os penis to simulate
      obstruction. Uroliths (calcium oxalate, urate, or magnesium ammonium phosphate)
      were fragmented by Ho:YAG laser, in contact mode through a 320 micro optic fiber,
      passed through the operating channel of a 2.8 mm flexible endoscope. The time and
      total energy to fragmentation were recorded. Dogs were euthanatized immediately
      after lithotripsy (3 dogs) or at 3 days (7 dogs), and urethral lesions and any
      stone remnants were evaluated. Urethral integrity was also evaluated in 9 other
      dogs by endoscopy on day 10; these were also monitored clinically for 30 days.
      RESULTS: The mean time for adequate fragmentation was 166.7 seconds (range, 47
      494.5 seconds). The mean+/-SD energy used was 1418+/-851.2 J. In part 1, 2 dogs
      were obstructed with urolith fragments at necropsy. Eight dogs had minimal (<30
      mg) or no urolith material evident within the urethra. Four dogs had gross focal
      or circumferential erosion, ulceration, or hemorrhage of the urethral mucosa.
      Lesions were not associated with the site of laser irradiation in 2 dogs. In dogs
      observed for 30 days, hematuria, pollakiuria, and stranguria that were observed
      after lithotripsy, resolved in all affected dogs by day 5. No mucosal lesions
      were observed by endoscopy and none of the dogs became obstructed. CONCLUSION:
      Laser lithotripsy with the Ho:YAG laser in contact mode successfully fragmented
      obstructive uroliths in male dogs. CLINICAL RELEVANCE: Laser lithotripsy may be a
      clinically relevant technique for treatment of urolithiasis in male dogs;
      clinical studies to evaluate long-term effects on urethral mucosa and the role of
      repeat treatment for recurrence are indicated.

PMID- 14687188
TI  - Comparison of laparoscopic ovariohysterectomy and ovariohysterectomy in dogs.
AB  - OBJECTIVES: To evaluate technique, complication rates, postoperative pain scores,
      and clinical outcomes in dogs after laparoscopic ovariohysterectomy (LOVH) or
      traditional ovariohysterectomy (OVH). STUDY DESIGN: Prospective clinical trial.
      ANIMALS OR SAMPLE POPULATION: Thirty-four intact female dogs, weighing 2.4-31 kg.
      METHODS: LOVH (16 dogs) was performed by ligation of the uterus and ovaries with
      surgical wire, and then removal by an assisted laparoscopic technique. OVH was
      performed in 18 dogs. Subjective and objective pain scores were assigned at 0, 2,
      8, and 24 hours. Surgical time, complications, and pain and incision scores were
      evaluated. Dogs were followed for up to 6 months. RESULTS: The mean surgical time
      for LOVH (120 minutes; range, 47-175 minutes) was significantly longer than for
      OVH (69 minutes; range, 25-140 minutes). Significantly lower pain scores
      (subjective, in 2 of 10 categories; objective, in 8 of 10 categories) were
      identified with LOVH at 1 or more time periods. Surgical complications with LOVH
      were postoperative fever and anorexia (1 dog), minor splenic (3) or pedicle
      hemorrhage (4), intermittent vaginal hemorrhagic discharge (1), and suture
      reaction (3). Surgical complications with OVH were hemorrhage from an ovarian
      pedicle requiring reoperation (1 dog), dehiscence of the abdominal wall (1), and
      seroma (1). Anesthetic complications included hypotension in 8 OVH dogs and 1
      LOVH dog, and hypothermia in 4 OVH and 9 LOVH dogs. The mean incision scores were
      lower for LOVH at all time periods. CONCLUSION: LOVH was performed successfully
      in young nonparous dogs >10 kg. Surgical time and complication rates were
      greater; however, LOVH postoperative pain scores were < or =OVH scores. CLINICAL
      RELEVANCE: LOVH is a potentially safe surgical alternative to traditional OVH in
      dogs. Equipment cost and necessity for more than 1 surgeon may limit its
      usefulness in small animal practice.

PMID- 14687189
TI  - Spatial and temporal expression of types I and II receptors for transforming
      growth factor beta in normal equine skin and dermal wounds.
AB  - OBJECTIVE: To describe immunolocalization of TGF-beta receptors (RI and RII) in
      normal equine skin and in thoracic or limb wounds, healing normally or with
      exuberant granulation tissue (EGT). STUDY DESIGN: Group A: six wounds on one
      metacarpus and one midthoracic area. Group B: six wounds on both metacarpi, one
      of which was bandaged to stimulate EGT. Immunohistochemistry was used to detect
      RI and RII expression in wound margins. ANIMALS: Eight horses, randomly assigned
      to one of two study groups. METHODS: Neutralizing polyclonal anti-rabbit RI and
      RII antibodies were used to detect spatial expression of RI and RII in biopsies
      obtained before wounding, at 12 and 24 hours, and 5, 10 and 14 days after
      wounding. RESULTS: RI and RII were co-localized in both unwounded and wounded
      skin. There were no differences in cell types staining positively between tissues
      obtained from the limb and the thorax, or from normally healing limb wounds and
      limb wounds with EGT, at any time. Because of increased cellularity within EGT,
      staining intensity of limb wounds with 'proud flesh' was greater than limb wounds
      healing normally, and thoracic wounds, during the proliferative phase of repair.
      CONCLUSIONS: Strong expression of RI and RII, particularly in limb wounds with
      EGT, suggested that signalling for stimulation of matrix proteins is in place to
      contribute to scarring. CLINICAL RELEVANCE: This information may help determine
      the appropriate time for using receptor antagonists to prevent scarring of limb
      wounds of horses.

PMID- 14687190
TI  - Self-retaining braces for canine arthroscopy.
AB  - OBJECTIVE: To describe self-retaining braces for canine shoulder, elbow, hip, and
      stifle arthroscopy. STUDY DESIGN: Clinical design and application. SAMPLE
      POPULATION: Clinical patients admitted for elective arthroscopy. METHODS: Self
      retaining braces were designed and constructed from commercially available
      products, steel tubing, and upholstery. The design efficacy was determined by
      clinical use. RESULTS: A shoulder/hip retraction device was constructed from a
      heavy-duty Mayo stand and a steel T frame. An elbow brace and a stifle brace were
      constructed from a commercially available positioning arm and steel tubing. These
      devices were used successfully in clinical canine arthroscopy and provided
      consistent stability for arthroscopic surgery without the need of a surgical
      assistant. CONCLUSIONS: Arthroscopic self-retaining braces can be constructed
      from commercially available products and other simple materials to provide
      reliable patient positioning without the need for a surgical assistant. CLINICAL
      RELEVANCE: Self-retaining braces may provide improved patient stabilization and
      eliminate the need for a surgical assistant in most cases of canine arthroscopy.

PMID- 14687191
TI  - An in vitro biomechanical comparison of a prototype intramedullary pin-plate with
      a dynamic compression plate for equine metacarpophalangeal arthrodesis.
AB  - OBJECTIVES: To compare the biomechanical properties of a prototype intramedullary
      pin-plate (IMPP) implant specifically designed for equine metacarpophalangeal
      (MCP) arthrodesis with a dynamic compression plate (DCP) system. STUDY DESIGN: In
      vitro biomechanical testing of paired cadaveric equine forelimbs with a simulated
      traumatic disruption of the suspensory apparatus, stabilized by one of two
      methods for MCP arthrodesis. ANIMAL POPULATION: Twenty-one pairs of adult equine
      cadaveric forelimbs. METHODS: Each forelimb had the distal sesamoidean ligaments
      severed to create a disrupted suspensory apparatus. For each forelimb pair, the
      MCP joint was stabilized with the IMPP in one limb, and a DCP in the other limb.
      Seven matching limb pairs were tested in axial compression in a single cycle to
      failure, 7 matching limb pairs were tested in torsion in a single cycle to
      failure, and 7 matching limb pairs were fatigued tested in axial compression.
      Mean test variable values for each method were compared using a paired t-test
      within each group. Significance was set at P<.05. RESULTS: The mean yield load,
      yield stiffness, and failure load (axial compression, torsional loading) was
      significantly greater for the IMPP compared with the DCP system. Mean cycles to
      failure for axial compression was significantly greater for the IMPP compared
      with the DCP system. Significance in all tests was P<.0001. CONCLUSION: The IMPP
      was superior to the DCP system in resisting the biomechanical forces most likely
      to cause failure of MCP joint arthrodesis. CLINICAL RELEVANCE: The IMPP implant
      should be considered for MCP arthrodesis in horses with traumatic disruption of
      the suspensory apparatus. The specific design of the IMPP implant may facilitate
      equine MCP arthrodesis and avoid convalescent complications related to cyclic
      fatigue.

PMID- 14687192
TI  - Laparoscopic repair of a small intestinal mesenteric rent in a broodmare.
AB  - OBJECTIVES: To describe standing laparoscopic repair of mesoduodenal rent
      inaccessible by ventral median celiotomy. STUDY DESIGN: Clinical case report.
      SAMPLE POPULATION: A 6-year-old Thoroughbred broodmare with a right displacement
      of the dorsal colon and small intestinal incarceration in a mesoduodenal rent.
      METHODS: Two days after correction of a right dorsal displacement of the
      ascending colon, small intestinal incarceration, and partial closure of
      mesoduodenal rent, standing left and right flank laparoscopy was used to explore
      the abdomen to identify the mesoduodenal defect. The mesenteric rent was repaired
      from right flank portals by approximation with hemostatic clips. RESULTS:
      Approximation of the mesoduodenal rent was achieved with laparoscopic clips. No
      further complications or signs of abdominal pain occurred over the following
      year. CONCLUSIONS: Mesenteric rents in the mesoduodenum can be repaired by
      laparoscopic techniques in the standing horse. CLINICAL RELEVANCE: Use of
      laparoscopic techniques in the standing horse should be considered for
      mesoduodenal rents that are not accessible form a ventral median celiotomy.

PMID- 14687193
TI  - Genesis of the surgical forum: A historical view of the American College of
      Veterinary Surgeons.

PMID- 14687195
TI  - Visualisation of "Marx's line" along the marginal eyelid conjunctiva of human
      subjects with lissamine green dye.
AB  - PURPOSE: To qualitatively assess the frequency and intensity of the staining of
      Marx's line with lissamine green dye. METHODS: Eighty-five non-contact lens
      wearers, aged 18-78 years and of white (European) or Arabic origin, were
      assessed. The subjects had no major eye disease, although some had mild-to
      moderate congestion of the main tarsal (Meibomian) glands and/or anterior
      blepharitis. Lissamine green dye strips were used to stain the marginal zone of
      the palpebral conjunctiva, and then high magnification photo slitlamp images were
      taken. RESULTS: A lissamine green staining line was unmistakable in 83 of the
      subjects, and just evident in the other two. The line extends along the entire
      length of the upper and lower lid margins, and the staining broadens and extends
      over the puncta. In most subjects, the lissamine green-stained line was posterior
      to the main tarsal gland orifices, but in five subjects it was distinctly
      anterior to the orifices. In over two-thirds of the subjects, the width of line
      was much less than the distance between the gland orifices, and was at a similar
      distance to its width from the orifices. However, in one-third of the subjects,
      the width of the line was around half that of the distance between the orifices
      or slightly greater (i.e. approximately 0.5 mm), and this feature was more
      commonly present in those of non-European origin. CONCLUSION: Lissamine green dye
      highlights a very distinct line of cells along the marginal zone, and should be a
      useful tool to visualise this feature. This line of cells is thought to be the
      natural site of contact between the eyelid margin and the surfaces of the bulbar
      conjunctiva and cornea.

PMID- 14687196
TI  - Chronic open angle glaucoma: patient awareness of the nature of the disease,
      topical medication, compliance and the prevalence of systemic symptoms.
AB  - PURPOSE: To study the awareness of the nature of the disease, compliance with
      treatment, and prevalence of systemic symptoms in a group of patients with
      chronic open angle glaucoma (COAG). METHOD: A structured questionnaire was
      designed and given to 260 consecutive COAG patients attending a general
      ophthalmology clinic. Questions related to the increased risk of COAG amongst
      family members, screening of family members, nature of field defects, variation
      in IOP, topical treatment and availability of a free eye test for a COAG patient
      in the UK were asked. Compliance and systemic symptoms were also assessed.
      RESULTS: Forty-one per cent (107 of 260) of patients in the study group were
      aware of the increased risk of COAG in family members and 45.5% (118 of 260) of
      patient's family members had undergone screening for COAG. Seventy-three per cent
      (191 of 260) of the patients were aware of their own and their family members'
      entitlement to a free eye test. Seventy-seven per cent of patients claimed full
      compliance. Thirty per cent of patients were noted to have systemic symptoms.
      CONCLUSIONS: The awareness of the nature of COAG in this population was low and
      incidence of perceived drug related systemic symptoms very high. Both of these
      may contribute to poor compliance.

PMID- 14687197
TI  - Effect of light filters on reading speed in normal and low vision due to age
      related macular degeneration.
AB  - PURPOSE: To investigate the effects of light filters on reading speed in normal
      and low vision due to age-related macular degeneration (AMD). METHODS: Reading
      speed was determined for 12 subjects with normal vision and 12 subjects with non
      exudative AMD using stationary lowercase nonsensical print in Times Roman font
      and four light filters; a yellow Corning Photochromic Filter (CPF) 450, a grey
      neural density (ND) filter, an individual filter obtained using the Intuitive
      Colorimeter and a clear filter. RESULTS: There was no statistically significant
      light filter effect on reading speed for the normal subjects. The AMD group
      demonstrated a statistically significant 5% average improvement in reading speed
      with the CPF450 compared with the other filters although some AMD subjects had
      improvements of 10-15%. CONCLUSIONS: Light filters obtained using the Intuitive
      Colorimeter(R) performed poorly when compared with the CPF450, ND and clear
      filters for both the study groups. For the AMD group, average reading speed was
      statistically greater with the CPF450 than the other filters, however it is
      questionable whether the improvement (5%) would be clinically significant. As
      some of the subjects with AMD had greater improvements with the CPF450 we
      advocate clinical assessment of light filters using existing protocols on an
      individual basis.

PMID- 14687198
TI  - Cling film as a barrier against CJD in Goldmann-type applanation tonometry.
AB  - PURPOSE: To determine the feasibility of taking intra-ocular pressure (IOP)
      readings with Goldmann-type applanation tonometer probe covered with cling film
      to avoid transmission of Creutzfeldt-Jakob disease (CJD). METHODS: Data were
      collected on two occasions from the right eyes of 30 healthy subjects using a
      Perkins applanation tonometer. On each occasion, a single tonometry measurement
      was made with and without cling film covering. RESULTS: Cling film covering
      brought about a statistically significant IOP bias (-0.8 mmHg on first occasion
      and -1.17 mmHg on second occasion). The 95% limits of agreement, between readings
      made with and without cling film covering, were +/-3.4 mmHg on first occasion; +/
      2.5 mmHg on second occasion. A statistically significant reduction of inter
      sessional repeatability was observed for readings taken with cling film (+/-5.2
      mmHg) compared to those made without (+/-3.9 mmHg). CONCLUSIONS: Even if the
      above findings are found to be acceptable, given the known intra-subject
      variations of this type of tonometry (+/-4 mmHg), ethical and legal
      considerations relating to the barrier properties of cling film are likely to
      prevent its routine use by optometrists.

PMID- 14687199
TI  - Is eye size related to orbit size in human subjects?
AB  - The purpose of this study is to determine if there is an association between eye
      size and the volume of the orbit in adult subjects. Thirty-three subjects with
      varying degrees of ametropia (+1.00 to -12.75 D) underwent magnetic resonance
      scan of the orbit. Results show that the larger myopic eye was not associated
      with a larger orbit.

PMID- 14687200
TI  - The relationship between intraocular pressure and refractive error adjusting for
      age and central corneal thickness.
AB  - PURPOSE: To investigate the relationship between intraocular pressure (IOP) and
      refractive errors after adjusting for age, central corneal thickness (CCT), and
      other related factors. METHODS: IOP, CCT and refractive errors were measured in
      the right eyes of 1855 subjects, aged 40-82 years, in a cross-sectional study
      design. Subjects were divided into groups by refractive status: hyperopia,
      emmetropia, mild myopia, moderate myopia, or high myopia. With adjustments for
      age, CCT, blood pressure, obesity, education, hypertension, diabetes, and smoking
      status, IOP was estimated for each refractive status using a general linear
      model. RESULTS: IOP increased with advancing degrees of myopia, even after
      adjustment for age, CCT, and other related factors (p = 0.011). Estimated IOP of
      moderate myopia was significantly higher than that of emmetropia (p = 0.022).
      CONCLUSIONS: Our results confirm the positive association between IOP and
      increasing degrees of myopia. This finding would support the hypothesis that the
      relationship between glaucoma and myopia might be pressure mediated.

PMID- 14687201
TI  - Prevalence of refractive errors in teenage high school students in Singapore.
AB  - We aimed to study the prevalence of refractive conditions in Singapore teenagers.
      Grade 9 and 10 students (n = 946) aged 15-19 years from two secondary schools in
      Singapore were recruited. The refractive errors of the students' eyes were
      measured using non-cycloplegic autorefraction. Sociodemographic data and
      information on risk factors for myopia (such as reading and writing) were also
      obtained using an interviewer-administered questionnaire. The prevalence of
      refractive conditions was found to be: myopia [spherical equivalent (SE) at least
      -0.50 D] - 73.9%, hyperopia (SE at least +0.50 D) - 1.5%, astigmatism (cylinder
      at least -0.50 D) - 58.7% and anisometropia (SE difference at least 1.00 D) -
      11.2%. After adjusting for age and gender, currently doing more than 20.5 h of
      reading and writing a week was found to be positively associated with myopia
      [odds ratio 1.12 (95% CI 1.04-1.20, p = 0.003)], as was reading and writing at a
      close distance and a better educational stream. The prevalence of myopia (73.9%)
      in Singapore teenagers is high. Current reading and writing habits, reading at
      close distances and a better educational stream are possible risk factors for
      myopia.

PMID- 14687202
TI  - How big does a coloured overlay have to be?
AB  - Coloured overlays and coloured lenses can both increase reading speed, but when
      they do their colour is not necessarily the same, suggesting that the beneficial
      effects of a coloured filter might depend upon the area of the visual field that
      it colours. We investigated the effects of overlays on reading speed and varied
      the size of the overlay and the colour of the surround. Children who had been
      assessed with coloured overlays were required to read a passage of randomly
      ordered common words. The words were printed in black ink as a block of text
      positioned centrally on an A4 page of white paper in landscape orientation. The
      speed of reading was compared under four conditions: (1) without an overlay; (2)
      with an overlay of the chosen colour covering the entire page; (3) with the
      overlay cut so that it just covered the text but left the margin white; (4) with
      the overlay of the chosen colour covering the text but with the margin coloured a
      complementary colour, using a second overlay. The children who were using an
      overlay read more quickly with the overlay; those who were no longer using the
      overlay did not. Although the block of text covered less than half the page, the
      colour and nature of the margin did not affect reading speed significantly. These
      findings suggest that in order to be effective at improving reading speed an
      overlay needs to cover the text, but not necessarily the remainder of the page,
      which means that smaller overlays may sometimes be sufficient.

PMID- 14687203
TI  - Age-related macular degeneration and nutritional supplementation.

PMID- 14687208
TI  - The effect of copper on the death rate of Salmonella typhimurium DT104:30 in food
      substrates acidified with organic acids.
AB  - AIMS: The objective of this study was to investigate the effect of copper ions on
      the survival of Salmonella typhimurium DT104:30 in acidified liquid food
      substrates. METHODS AND RESULTS: The decimal reduction time (Dvalue) of Salm.
      typhimurium DT104:30 was determined in acidified liquid pig feed (LPF) and
      skimmed milk (SM) containing a range of copper concentrations (0-50 ppm). As
      copper concentration increased, the death rate of Salm. typhimurium DT104:30
      increased. In LPF acidified with 150 mmol l-1 lactic acid the presence of 50 ppm
      copper resulted in a 10-fold increase in the death rate. CONCLUSIONS: The
      presence of copper salts in acidic liquid food substrates significantly increases
      the death rate of Salm. typhimurium DT104:30. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This finding could influence policy on levels of copper in pig feed.

PMID- 14687209
TI  - Rhodovulum sulfidophilum in the treatment and utilization of sardine processing
      wastewater.
AB  - AIMS: Rhodovulum sulfidophilum was grown in settled undiluted and nonsterilized
      sardine processing wastewater (SPW). The aims were to evaluate the effects of
      inoculum size and media on the biomass production with simultaneous reduction of
      chemical oxygen demand (COD). METHODS AND RESULTS: Three levels of inoculum size
      (10, 20 and 30% v/v) developed in glutamate-malate media (GMM) or settled and
      undiluted SPW were compared. The highest biomass (4.8 g l-1) was obtained after
      96-h culture with 20% (v/v) inoculum size, but the reduction in COD of SPW was
      the highest (85%) after 120-h culture with a 30% (v/v) inoculum developed in GMM.
      In cultures with inoculum developed in SPW the COD reduction in SPW was 79-83%.
      CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: Inoculum developed in GMM
      supported good growth of Rv. sulfidophilum in settled undiluted SPW and
      subsequent reduction in COD. A conceptual model was proposed for the treatment
      and utilization of SPW.

PMID- 14687210
TI  - Isolation of endophytic diazotroph Pantoea agglomerans and nondiazotroph
      Enterobacter asburiae from sweetpotato stem in Japan.
AB  - AIMS: To isolate and identify diazotrophic endophytes in the stem of Japanese
      sweetpotato cv. Koganesengan. METHODS AND RESULTS: Surface-sterilized and thinly
      sliced (1-2 mm) sweetpotato stem samples were incubated in test tubes with semi
      solid modified Rennie (MR) medium. The test tubes were assayed for acetylene
      reduction activity (ARA) 5 days after incubation at 30 degrees C. Twelve isolates
      were obtained from MR plates inoculated with a loop of semi-solid MR medium from
      ARA+ tubes. However, ARA test showed that only nine isolates were diazotrophic
      and three were nondiazotrophic strains. Using the API 20E diagnostic kit, four
      diazotrophic isolates were identified as strains of Pantoea spp. and five
      isolates as Klebsiella spp. The nondiazotrophic bacteria were strains of
      Enterobacter spp. A diazotrophic isolate Pantoea sp. MY1 and nondiazotrophic
      isolate Enterobacter sp. MY2 were identified to the species level by full
      sequence analysis of 16S rRNA gene. The results showed that MY1 had 99.2%
      similarity to Pantoea agglomerans ATCC 27155 and MY2 had 99.5% similarity to
      Enterobacter asburiae ATCC 35953. CONCLUSION: The stem of sweetpotato cv.
      Koganesengan was colonized by diazotrophic endophyte P. agglomerans and
      nondiazotrophic endophyte E. asburiae. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study is an essential step toward understanding the ecology and interaction
      between endophytic bacteria and sweetpotato.

PMID- 14687211
TI  - Difference and consensus of whole cell Salmonella enterica subsp. enterica
      serovars matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry spectra.
AB  - AIM: Application of MALDI-TOF MS for characterization of strains of Salmonella
      enterica subsp. enterica. METHODS AND RESULTS: Whole cells were analysed by MALDI
      TOF MS. Spectra with a maximum of 500 mass peaks between (m/z) 0 and 25000 were
      examined for consensus peaks manually and by a computer software algorithm.
      Consensus peaks were observed by both methods for spectra of Salmonella enterica
      serovars Derby, Hadar, Virchow, Anatum, Typhimurium and Enteritidis. CONCLUSIONS:
      Differences in numbers of consensus peaks in spectra obtained by manual and
      computer comparison indicated that development of the software involving
      statistical analysis of peak accuracy is necessary. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Development of an analysis system for peak profiles in whole cell
      MALDI-TOF MS spectra to enable intra and interlaboratory comparison.

PMID- 14687212
TI  - Streptomyces sp. 173, an insecticidal micro-organism from marine.
AB  - AIMS: To find new insecticidal antibiotics from marine micro-organisms. METHODS
      AND RESULTS: Strains isolated from seawater and sea sediments from Beidiahe and
      Dagang of the east coast of China were screened for their insecticidal qualities.
      The screening was carried out using bioassay of brine shrimp and the insect pest
      Helicoverpa armigera. The fermentation, preliminary extraction and isolation of
      Streptomyces sp.173 were carried out. CONCLUSIONS: In total 331 isolates were
      examined through bioassay of brine shrimp and 40 isolates (12.08%) showed
      potential insecticidal activities. Of the 40 isolates, one isolate, designated
      Streptomyces sp.173, was found to have strong insecticidal activity against both
      brine shrimp and H. armigera, similar to that of avermectin B1. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The isolated Streptomyces sp.173 has great insecticidal
      potency. This work indicated that marine micro-organisms could be an important
      source of insecticidal antibiotics and the improved anti-brine shrimp bioassay is
      suitable for primary screening.

PMID- 14687213
TI  - Impact of cultivation conditions on haemolytic activity of Pseudoalteromonas
      issachenkonii KMM 3549T.
AB  - AIMS: The present work aimed to study the effects of cultivation conditions on
      the haemolytic activities of Pseudoalteromonas issachenkonii. METHODS AND
      RESULTS: The kinetics of growth and haemolytic activities was investigated on sea
      salts and NaCl-based nutrient media supplemented with either starch, or KBr over
      a period of 140 h. The first haemolytic activity occurred when bacterial cells
      reached the late stationary phase. The second haemolytic activity was observed in
      marine broth (MB) after 110 h of incubation. Addition of Fe to the culture medium
      neither affected bacterial growth nor reduced the haemolytic activity. However,
      the activity was enhanced in the presence of iron chelator. The second haemolytic
      activity was not affected by Ca2+, or inhibited by chymotrypsin or EDTA.
      CONCLUSIONS: The production of haemolysins by P. issachenkonii was greater on MB
      and was dependent on both the medium composition and time of incubation. The
      second haemolytic activity was heat stable, nonproteinaceous, calcium-independent
      and was regulated by Fe. SIGNIFICANCE AND IMPACT OF THE STUDY: The results
      demonstrated the importance of optimization of both the media composition and
      monitoring the haemolytic activity over a prolonged cultivation time to detect
      different types of haemolysins.

PMID- 14687214
TI  - Molecular approach for analysis of model fungal genes encoding ligninolytic
      peroxidases in wood-decaying soil systems.
AB  - AIMS: Test the use of nondegenerated consensus polymerase chain reaction (PCR)
      primers targeting lip and mnp sequences to detect ligninolytic fungi in wood
      decaying soil systems, avoiding the need for enrichment or isolation on
      traditional fungal media culture. METHODS AND RESULTS: The PCR primers were
      tested with total DNA isolated from incubations of wood-soil systems inoculated
      or not with the white-rot fungi Phanerochaete chrysosporium, or a white-rot
      sample obtained from a Nothofagus forest. The PCR products for lip and mnp
      sequences were only obtained in soil with P. chrysosporium-colonized wood chips.
      In these soil samples, reverse transcription-PCR analysis of lip and mnp PCR
      products indicated expression of LipA, LipB, LipJ and MnP isoenzymes.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first assessment of the use of
      consensus PCR primers for direct detection of ligninolytic peroxidase genes in
      wood-decaying soil systems.

PMID- 14687215
TI  - Effect of the nitrogen source on caffeine degradation by Aspergillus tamarii.
AB  - AIMS: To evaluate caffeine degradation and nitrogen requirements during
      Aspergillus tamarii growth in submerged culture. METHODS AND RESULTS: Aspergillus
      tamarii spores produced on a coffee infusion agar medium added with sucrose were
      used. Several caffeine and ammonium sulphate concentrations (0-1 and 0-1.36 g l
      1, respectively) were tested simultaneously on fungal biomass production and
      caffeine degradation. An additional caffeine pulse (4 g l-1) was added for all
      experiments after 48 h of fermentation. Results revealed that when using 0.90 g l
      1 of caffeine and 0.14 g l-1 of ammonium sulphate, biomass production and
      caffeine degradation were enhanced. Highest biomass production (Xmax = 9.87 g l
      1) with a specific growth rate (micro) of 0.073 h-1 and caffeine degradation rate
      of 0.033 g l-1 h-1, was observed under these conditions. CONCLUSIONS: Caffeine
      degradation as well as biomass production were characterized. SIGNIFICANCE AND
      IMPACT OF THE STUDY: These studies set the stage for future characterization
      studies of intracellular enzymes involved in caffeine degradation. Moreover,
      results observed may help in the biotreatment of residues from the coffee
      agroindustry.

PMID- 14687216
TI  - Enumeration of Escherichia coli O157 in cattle faeces using most probable number
      technique and automated immunomagnetic separation.
AB  - AIMS: To determine the numbers of Escherichia coli O157 present in the faeces of
      naturally infected cattle. METHODS AND RESULTS: A combination of the most
      probable number (MPN) technique and automated immunomagnetic separation (AIMS)
      was used to enumerate E. coli O157 in cattle faeces from both pasture-fed and
      grain-fed animals. A total of 22 E. coli O157 positive faecal samples were
      enumerated for E. coli O157 (10 from pasture-fed and 12 from grain-fed animals).
      The numbers of E. coli O157 in cattle faeces varied from undetectable (<3 MPN g-1
      of faeces) to 2.4 x 104 MPN g-1. There was no significant difference (P = 0.06)
      between the numbers of E. coli O157 in pasture-fed or grain-fed cattle faeces,
      although the geometric mean (antilog of the mean of log10 transformed MPN values)
      was higher in grain-fed (130 MPN g-1) than in pasture-fed (13 MPN g-1).
      CONCLUSIONS: Although the number of samples tested is small, the results indicate
      that E. coli O157 make up a small proportion of the total E. coli population
      present in cattle faeces. SIGNIFICANCE AND IMPACT OF THE STUDY: Information on
      the numbers of E. coli O157 present in cattle will assist in developing more
      robust quantitative risk assessments and formulating intervention strategies.

PMID- 14687217
TI  - In vitro inhibition of microbial flora of fish by nisin and lactoperoxidase
      system.
AB  - AIMS: To test the antimicrobial effects of nisin and lactoperoxidase system (LP
      system) against sardines flora. This study is part of a programme designed to
      investigate the preservability of fish using these inhibitors as potential
      biopreservatives. METHODS AND RESULTS: Antimicrobial effects of nisin and LP
      system alone or in combination were tested by the agar diffusion method against
      bacterial strains isolated from sardines (Sardina pilchardus). Nisin inhibited
      only Gram-positive bacteria, whereas LP system inhibited all strains studied. The
      combination of nisin (100 IU ml-1) and LP system (10 level) was significantly
      more effective than LP system or nisin alone against all strains, excepting
      Aeromonas salmonicida subsp. salmonicida and Vibrio alginolyticus. CONCLUSION:
      These results clearly demonstrated the efficiency of LP System-nisin combination
      for inhibiting spoilage flora of fish. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Because LP system has a broad activity spectrum, it may be an interesting
      additional hurdle to improve the safety of food preservation by nisin.
      Combination of nisin and LP system could be of great interest as biopreservatives
      for fish and fish products.

PMID- 14687218
TI  - Chicken juice, a food-based model system suitable to study survival of
      Campylobacter jejuni.
AB  - AIMS: The purpose of this study was to develop a food-based model system that
      resembles the environment that Campylobacter jejuni experiences on raw poultry
      products and use this model system to investigate growth and survival of the
      bacterium. METHODS AND RESULTS: Chicken juice was collected from frozen chickens
      and subsequently cleared by centrifugation and subjected to sterile filtration.
      At low temperatures (5 and 10 degrees C) C. jejuni NCTC11168 remained viable in
      chicken juice for a remarkably longer period of time than in the reference medium
      BHI. When exposed to heat stress (48 degrees C) C. jejuni NCTC11168 also showed
      increased viability in chicken juice compared with the reference medium.
      Furthermore, agar plates made with chicken juice supported growth of four
      clinical isolates of C. jejuni and a C. jejuni strain obtained from chicken at
      both 37 and 42 degrees C. CONCLUSIONS: Our work shows that minimal processed and
      sterilized chicken juice is an ideal environment for survival of C. jejuni and
      that it is useful as a food-based model system. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The developed model system may contribute to the understanding of C.
      jejuni viability on poultry products and can be instrumental in the development
      of alternative preservation strategies.

PMID- 14687219
TI  - Incubation time and water activity effects on ochratoxin A production by
      Aspergillus section Nigri strains isolated from grapes.
AB  - AIMS: The objective of this study was to determine the temporal ochratoxin A
      (OTA) accumulation profile of Aspergillus section Nigri at different water
      activity (aw) levels. METHODS AND RESULTS: Two Aspergillus carbonarius and two
      Aspergillus niger aggregate strains isolated from grapes were tested in vitro for
      OTA accumulation at 25 degrees C on synthetic nutrient medium, over periods of 20
      days at different aw levels. Results were modelled by a multiple linear
      regression and response surface predictive models were obtained. High levels of
      aw favoured OTA production by these moulds. Maximum amounts of OTA were found at
      the earlier growth states (5 days for A. carbonarius and 7-13 days for A. niger
      aggregate). CONCLUSIONS: Provided that A. section Nigri, and mainly A.
      carbonarius, play the main role in OTA presence in grapes, it would be critical
      to adjust the harvest and processing time to significantly reduce the chances for
      OTA accumulation. SIGNIFICANCE AND IMPACT OF THE STUDY: Ochratoxin A production
      by A. section Nigri has been shown for the first time to occur optimally after as
      little as 5 days on a grape-like medium.

PMID- 14687221
TI  - Interaction of Porphyromonas gingivalis with low-density lipoproteins:
      implications for a role for periodontitis in atherosclerosis.
AB  - OBJECTIVE: The association of periodontitis with atherosclerosis has been
      suggested from epidemiological studies. Recently, we have reported that
      macrophages stimulated by Porphyromonas gingivalis formed foam cells in the
      presence of low-density lipoproteins (LDL). In this study, we examined the direct
      interactions between LDL and P. gingivalis. METHODS: We investigated the
      aggregation of LDL with P. gingivalis and its outer membrane vesicles (OMVs),
      degradation of the apo B-100 protein of LDL by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and western blot analyses, as well
      as the effects of protease inhibitors or activators on the mobility of LDL by
      agarose gel shift assays. The binding of P. gingivalis or its OMVs with LDL was
      demonstrated by western blot analysis. We also examined whether or not the
      aggregated LDL induced foam cell formation from murine macrophages. RESULTS: LDL
      was aggregated in a dose-dependent manner with P. gingivalis and its OMVs.
      Moreover, degradation of the apo B-100 protein of LDL was directly demonstrated
      in the presence of P. gingivalis or its OMVs. Furthermore, the gel shift assays
      indicated that the mobility of LDL was increased in the presence of P.
      gingivalis. This alteration was attenuated in the presence of the protease
      inhibitors TLCK and leupeptin and increased in the presence of reducing agents.
      Moreover, LDL was bound to specific proteins of P. gingivalis suggesting that
      these proteins may also play a role in aggregation. Finally, the aggregated LDL
      induced murine macrophages to form foam cells. CONCLUSIONS: These results suggest
      that P. gingivalis may stimulate foam cell formation, in part, by aggregating LDL
      by proteolysis of apo B-100.

PMID- 14687222
TI  - Expression of CD73/ecto-5'-nucleotidase on human gingival fibroblasts and
      contribution to the inhibition of interleukin-1alpha-induced granulocyte
      macrophage colony stimulating factor production.
AB  - BACKGROUND AND OBJECTIVES: CD73/5'-nucleotidase (5'-NT) is an ectoenzyme that
      participates in immune/inflammatory reactions. We examined the possible
      expression of CD73/5'-NT on human gingival fibroblasts (hGF), which are important
      to the immune/inflammatory system in periodontal tissue. METHODS AND RESULTS: We
      demonstrated that CD73/5'-NT was expressed on hGF by flow cytometry. We found
      that pre-treatment of hGF with 5'-AMP induced marked inhibition of granulocyte
      macrophage colony-stimulating factor (GM-CSF) production from hGF upon
      stimulation with interleukin-1alpha (IL-1alpha) by enzyme-linked immunosorbent
      assay (ELISA). A specific inhibitor of 5'-NT, adenosine 5'-[alpha,beta-methylene]
      diphosphate blocked the inhibition of GM-CSF production, suggesting that
      adenosine converted from 5'-AMP acts on the inhibitory effects. The GM-CSF
      inhibition suggested that A3 receptor might be involved. The rank order of
      agonists was found to be (N6-benzyl-5'-N-ethylcarboxamidoadenosine) A3 receptor
      agonist > or = (2-chloroadenosine) non-selective agonist > (CGS-21680) A2A
      receptor agonist > adenosine > or = (N6-cyclohexyladenosine) A1 agonist. Further
      support for the main role of A3 receptor was the binding A3 antagonist [9-chloro
      2-(2-furanyl)-5-([phenylacetyl]amino)[1,2,4]-triazolo[1,5-c]quinazdine] reversed
      the effect of adenosine, but no significant reverse was observed by A1 (1,3
      dipropyl-8-cyclopentylxanthine), A2 [3,7-dimethyl-1-(2-propargyl)xanthine], A2A[8
      (3-chlorostyryl)caffeine], and A2B (alloxazine) antagonists. The CD73/5'-NT
      expression was increased upon stimulation with gamma-interferon, but not other
      stimulants such as tumor necrosis factor-alpha, IL-4, lipopolysaccharide from
      Porphyromonas gingivalis and Escherichia coli, and fimbriae from P. gingivalis,
      and this increase was correlated with the enhanced GM-CSF inhibition by 5'-AMP
      but not adenosine. CONCLUSIONS: These findings suggested that CD73/5'-NT on hGF
      exerts an anti-inflammatory effects in periodontal disease by conversion from 5'
      AMP to adenosine.

PMID- 14687223
TI  - Effects of sub-antimicrobial dose doxycycline therapy on crevicular fluid MMP-8,
      and gingival tissue MMP-9, TIMP-1 and IL-6 levels in chronic periodontitis.
AB  - OBJECTIVE: To investigate whether sub-antimicrobial dose doxycycline (SDD)
      therapy for 120 d in chronic adult periodontitis patients had significant effects
      on gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) levels, and
      on gingival tissue MMP-9, tissue inhibitor of matrix metalloproteinases-1 (TIMP
      1) and interleukin-6 (IL-6) levels. BACKGROUND: Tetracycline can significantly
      inhibit MMP activity in GCF and in gingival tissue, even in much lower dosage
      then a traditional antimicrobial dosage used in conventional therapy. Sub
      antimicrobial dose doxycycline (SDD) therapy has been shown to reduce periodontal
      disease activity to control MMP and pro-inflammatory cytokines. METHODS: A total
      of 32 patients with incipient to moderate (probing pocket depth approximately 4-7
      mm) chronic adult periodontitis were included in the study. Subjects were
      randomly assigned to two groups. After scaling and root planning (SRP), the SRP +
      SDD group received SDD, 20 mg bid, whereas the SRP + placebo group received
      placebo, 20 mg bid. In the follow-up, efficacy measures included the change in
      probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing
      (BOP) and gingival crevicular fluid MMP-8 levels, gingival tissue MMP-9, TIMP-1
      and IL-6 levels from baseline to 120 d. RESULTS: After 120 d, PD and CAL improved
      significantly in the SRP + SDD group. Initial MMP-8 levels for the SRP + SDD
      group and the SRP + placebo group were 407.13 +/- 114.45 ng/ml and 378.71 +/-
      189.39 ng/ml, respectively, with no statistical difference between the two
      groups. MMP-8 levels for the SRP + SDD group and the SRP + placebo group were:
      235.35 +/- 134.58 ng/ml and 364.04 +/- 219.27 ng/ml at 30 d; 157.50 +/- 95.95
      ng/ml and 236.60 +/- 186.16 ng/ml at 60 d; 102.70 +/- 67.64 ng/ml and 208.56 +/-
      124.54 ng/ml at 90 d; and 63.77 +/- 53.33 ng/ml and 229.13 +/- 168.09 ng/ml at
      120 d, respectively. The amount of decrease in MMP-8 levels for the SRP + SDD
      group was statistically significant compared to that for the SRP + placebo group,
      especially apparent at 120 d (p < 0.05). TIMP-1 levels in both groups increased
      from the baseline to 120 d with statistical significance (p-value < 0.05), but
      there was no significant difference between the two groups. Changes in MMP-9 and
      IL-6 levels were not statistically significant. CONCLUSION: Adjunctive SDD
      therapy can improve the clinical parameters and this clinical improvement is
      reflected by controlled level of MMP-8 in chronic adult periodontitis after the
      therapy.

PMID- 14687224
TI  - The effect of centrifugal force on mRNA levels of collagenase, collagen type-I,
      tissue inhibitors of metalloproteinases and beta-actin in cultured human
      periodontal ligament fibroblasts.
AB  - BACKGROUND: The aim of orthodontic treatment is to relocate teeth abnormally
      positioned in the jaws. This is achieved by application of continuous force on
      the tooth, which is immediately being sensed by the periodontal ligament (PDL),
      bone and the gingiva. Since the bony response is mediated by the PDL, tooth
      movement is primarily a PDL phenomenon. OBJECTIVES: Thus, the purpose of the
      present study was to evaluate the direct effect of force (excluding the in vivo
      tissue response) on the molecular level of matrix metalloproteinase-1 (MMP-1) and
      collagen type-I (Col-I) in human PDL fibroblasts. METHODS: PDL cell culture
      flasks were centrifuged for 10, 20, 30, 60, 90 and 120 min by horizontal
      microplate rotor. The effect of force on mRNA levels of beta-actin, MMP-1, Col-I,
      tissue inhibitors-1 and -2 (TIMPs) genes was analyzed by RT-PCR. RESULTS: The
      results showed that force had no effect on the mRNA levels of beta-actin during
      the first 90 min of application of force, indicating for the first time the use
      of beta-actin gene as an internal invariant control. It increased the mRNA levels
      of MMP-1 while almost no effect on Col-I and TIMPs was observed. CONCLUSIONS: The
      results indicate that PDL remodeling following application of orthodontic force
      could be partly attributed to the direct effect of the force on MMP-1 gene
      expression in fibroblasts.

PMID- 14687225
TI  - Accelerated alveolar bone loss in male HLA-B27 transgenic rats: adult onset.
AB  - OBJECTIVE AND BACKGROUND: HLA-B27 transgenic (TG) rats exhibit severe colitis,
      arthritis and other inflammatory lesions. Previous studies in female TG rats
      indicate that they develop severe alveolar bone loss (ABL). Lack of data on male
      TG rats has left open the question of possible hormonal/sex dependence for the
      observed ABL. The purpose of the present study was to assess the natural history
      of ABL in male HLA-B27 rats, compared to age- and sex-matched wild-type Fischer
      344 (WT) rats. MATERIALS AND METHODS: Fourteen WT and 11 TG male rats, aged 7-8
      weeks, were used. Sacrifice times occurred at 10, 22 and 35 weeks. Animal heads
      were defleshed and treated to remove organic material, and skulls were stained to
      locate the cemento-enamel junction. ABL was measured as exposed molar root
      surface area (mm2) on the right maxilla and right mandible. Blinded measurements
      were performed using a computer-assisted image analysis system. RESULTS: ABL for
      the entire TG group was significantly different from the WT group (p < 0.05).
      There was no significant difference in ABL between WT and TG rats at 10 weeks of
      age. At 22 and 35 weeks of age TG rats experienced 23% and 37% greater ABL than
      WT rats, respectively; these differences were statistically significant (p <
      0.015). For both TG and WT animals, ABL was significantly different between the
      three age groups. CONCLUSIONS: These results, consistent with previous findings
      in female TG rats, suggest that the accelerated ABL found in TG rats is an adult
      onset, age-dependent, and sex-independent process.

PMID- 14687226
TI  - Mineralized bone loss in partially edentulous trabeculae of ovariectomized rabbit
      mandibles.
AB  - OBJECTIVE: The purpose of this study was to evaluate trabeculae changes in
      partially edentulous bone in ovariectomized rabbits. BACKGROUND: Numerous
      clinical studies have suggested that the greater risk for oral bone loss in
      females may be correlated with osteoporosis after menopause. Knowledge of
      trabecular changes in partially edentulous bone in animals with loss of ovarian
      function may be beneficial in the diagnosis and treatment of partially edentulous
      patients of postmenopausal women. METHODS: Twelve adult female Japanese white
      rabbits were examined. The mandibular incisors were initially extracted to
      simulate the partially edentulous bone. Six animals were bilaterally
      ovariectomized and the other six sham-ovariectomized 12 weeks after tooth
      extraction. The partially edentulous parts of distal mandibular bodies were
      processed undecalcified 12 weeks after ovariectomized or sham-ovariectomized
      surgeries and examined by quantitative trabecular bone histomorphometry. RESULTS:
      In ovariectomized rabbits, there were significant increases in trabecular
      separation, osteoid volume, osteoid thickness, osteoid width, eroded surface, and
      mineral apposition rate, and a significant decrease in trabecular number.
      CONCLUSION: The results of sparser trabecular structure, more trabecular osteoid,
      and increased trabecular bone turnover demonstrate mineralized bone loss in
      partially edentulous trabeculae of ovariectomized rabbit mandibles and suggest
      that the same loss may occur in postmenopausal women.

PMID- 14687227
TI  - In situ expression of RANKL, RANK, osteoprotegerin and cytokines in osteoclasts
      of rat periodontal tissue.
AB  - OBJECTIVES: This study examined the in situ expression of receptor activator of
      nuclear factor-kappaB ligand (RANKL), receptor activator of nuclear factor-kappaB
      (RANK), osteoprotegerin, interleukin-1beta (IL-1beta) and tumor necrosis factor
      alpha (TNFalpha) in the osteoclasts of rat periodontal tissue. BACKGROUND: In
      periodontal disease, osteoclasts cause resorption of the alveolar bone. The
      function of osteoclasts is regulated by interaction with periodontal ligament
      cells (PDLs). Furthermore, various kinds of molecules such as RANKL, RANK,
      osteoprotegerin, IL-1beta and TNFalpha are known to be related to the osteoclasts
      differentiation and function. It is therefore important to observe the expression
      of RANKL, RANK, osteoprotegerin and cytokines in osteoclasts and PDLs. METHODS:
      Four-week-old Wistar rats were used. Tooth movement was performed by the Waldo
      method, and the pathological bone resorption was induced. The demineralized
      maxillae and mandiblae were embedded with paraffin. In situ hybridization was
      performed to detect RANKL, RANK, osteoprotegerin, IL-1beta, and TNFalpha mRNAs in
      osteoclasts and other cells using the specific RNA probes, respectively. RESULTS:
      Both RANKL and RANK were concomitantly expressed in some osteoclasts. RANKL was
      also positive in osteoblasts and PDLs. No IL-1beta- and TNFalpha-positive
      osteoclast was noted. The positive signals of osteoprotegerin were detected in
      almost all osteoblasts, PDLs and odontoblasts. No osteoprotegerin-positive
      osteoclasts were observed. The number and the distribution pattern of RANKL- and
      RANK-expressing osteoclasts changed when orthodontic excessive force was applied
      to periodontal tissue. In addition, IL-1beta and TNFalpha were shown to be
      expressed in osteoclasts under pathological status. CONCLUSION: These findings
      suggest that an autocrine mechanism of RANKL-RANK exists in osteoclast, which is
      heightened in the pathological conditions. Furthermore, the autocrine mechanism
      of IL-1beta and TNFalpha is also provided in osteoclast under pathological
      condition. These autocrine mechanisms therefore seem to regulate the osteoclast
      function in both physiological and pathological conditions.

PMID- 14687228
TI  - Effects of eight antibacterial agents on cell survival and expression of
      epithelial-cell- or cell-adhesion-related genes in human gingival epithelial
      cells.
AB  - OBJECTIVE AND BACKGROUND: Our previous studies suggest that little adverse effect
      on the growth of the periodontal ligament would be expected, if tetracycline,
      minocycline, ofloxacin, roxithromycin, clarithromycin, and azithromycin were
      topically administered to the periodontal pocket at their MIC90 doses required to
      inhibit the growth of 90% of periodontopathic bacteria, including Porphyromonas
      gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans. In
      the present study, we investigated the cytocidal effects of eight antibacterial
      agents on the human gingival epithelial cell line NDUSD-1. We also used NDUSD-1
      cells to examine the effects of these agents on the mRNA and protein expressions
      of genes associated with the proliferation, differentiation, or cellular adhesion
      important to the epithelial regeneration of the periodontal attachment. METHODS:
      The cytocidal effect of the test agents was measured as a decrease in cell
      survival. To obtain a quantitative measure of the cytocidal effect, the LD50,
      i.e. the concentration which results in a 50% decrease in cell survival relative
      to the controls, was extrapolated from the concentration-response curves. The
      effects of the agents on the mRNA and protein expressions in NDUSD-1 cells were
      studied by reverse transcription-polymerase chain reaction (RT-PCR) and western
      blot analyses, respectively. RESULTS: The cytocidal effect increased in a
      concentration-dependent manner as the concentration of each of the eight test
      agents increased. The order of the agents according to their cytocidal effects
      (LD50) was minocycline > tetracycline > enoxacin > clarithromycin > roxythromycin
      approximately ofloxacin > azithromycin > erythromycin. The cytocidal effects of
      minocycline, tetracycline, enoxacin, clarithromycin, roxythromycin, ofloxacin,
      and azithromycin ranged from 1.2 to 23.2 times greater than that of erythromycin.
      The maximum non-cytocidal concentrations (MNCCs) of these agents for NDUSD-1
      cells were: 0.3 microm for minocycline, 1 microm for tetracycline, 3 microm for
      ofloxacin and erythromycin, 10 microm for enoxacin, clarithromycin, and
      azithromycin, and 100 microm for roxythromycin. The MNCCs of ofloxacin,
      azithromycin, clarithromycin, and roxythromycin were greater than their MIC90
      concentrations for periodontopathic bacteria described above. The effects on the
      mRNA and protein expressions of epithelial-cell- or cell-adhesion-related genes
      were examined in NDUSD-1 cells exposed to clarithromycin, roxythromycin,
      ofloxacin, and azithromycin at their MNCCs. None of the agents affected the mRNA
      expressions of five genes: keratinocyte growth factor receptor, keratin 18,
      integrin beta1, integrin beta4, and laminin 5gamma2. Clarithromycin and ofloxacin
      slightly decreased the protein expression of integrin beta4. Roxythromycin
      markedly decreased the protein expressions of integrin beta4 and laminin 5gamma2.
      Azithromycin had little inhibitory effects on the protein expressions of any of
      the five genes. CONCLUSIONS: These results suggest that little, if any, adverse
      effects on growth, differentiation, and adhesion of basal epithelial cells would
      be expected with topical administration of clarithromycin, ofloxacin or
      azithromycin to the periodontal pocket at a dose equivalent to the MIC90. It is
      important to note, however, that the extrapolation of these findings to in vivo
      conditions has yet to be undertaken.

PMID- 14687229
TI  - Detection of subgingival calculus and dentine caries by laser fluorescence.
AB  - OBJECTIVES: Detection of subgingival calculus and dentine caries in the bottom of
      deep periodontal pockets is often difficult without visual observation. We thus
      examined the possibility of its detection using autofluorescence induced by laser
      irritation. METHODS: Autofluorescence was measured at various excitation and
      emission wavelength settings in five specimens each of sound dentine and enamel,
      subgingival calculus, and root caries. Periodontopathic model teeth with
      bacterial cells and blood clots were also irritated by laser to obtain
      autofluorescent images. RESULTS: Subgingival calculus and dentine caries showed a
      characteristic 700 nm emission when excited at 635 nm or a 720 nm emission when
      excited at 655 nm; sound dentine or enamel, however, did not. The calculus
      differentiation power, however, was higher with excitation at 635 nm than at 655
      nm. The autofluorescent images photographed at an excitation of 633 nm provided
      clear calculus identification in periodontopathic model teeth when a 700 nm band
      pass filter or a 700 nm high-pass filter was used. However, fluorescence
      intensity was masked when the calculus surface was covered by bacterial cells or
      blood clots. For clinical use, it would be important to remove subgingival plaque
      and debris from root surfaces before attempting to detect subgingival calculus
      and root caries with this manner. CONCLUSION: The autofluorescence method
      employing excitation of 633-635 nm was found to be a powerful tool for detecting
      subgingival calculus and root caries.

PMID- 14687230
TI  - Vigabatrin-induced modification of Ki-67 expression in gingival epithelium:
      immunohistochemical study of a short series.
AB  - OBJECTIVE: To study the expression and role in vigabatrin (VGB)-induced gingival
      enlargement of Ki-67 antigen and p27KIP1, p21WAF1, and p53, proteins that
      activate or inhibit cell-cycle progression. MATERIALS AND METHODS: Six patients
      treated with VGB for partial epileptic seizures refractory to classic
      anticonvulsant treatment were studied. Gingival biopsies were taken from four of
      these patients for immunohistochemical studies; 10 control biopsies from
      individuals with healthy gingiva and 10 from patients with periodontal disease
      were also evaluated. RESULTS: Four of the six patients presented some degree of
      gingival enlargement (mild or moderate). Nuclear expression of Ki-67 was elevated
      (mean of 894 positive cells/mm2 in VGB-induced gingival enlargement vs. 391
      cells/mm2 in controls with healthy gingiva and 425 cells/mm2 in controls with
      periodontal disease) (p < 0.01, analysis of variance: anova), and nuclear
      expression of cyclin-dependent kinase (cdk) inhibitors p27KIP1 and p21WAF1 was
      reduced. The patients with gingival enlargement presented inflammatory infiltrate
      in lamina propria, mainly composed of T lymphocytes (CD3+) and plasma cells
      (CD38+), which was even more intense than in the biopsies of patients with
      periodontal disease. CONCLUSION: The overexpression of antigen Ki-67 and slight
      underexpression of cdk-inhibitors p27KIP1 and p21WAF1 suggest that VGB induced an
      increase in cell proliferation and contributed, together with concomitant
      periodontal disease, to the gingival enlargement.

PMID- 14687231
TI  - Expression of CD14, CD16 and CD45RA on monocytes from periodontitis patients.
AB  - BACKGROUND AND OBJECTIVE: Peripheral blood monocytes are a heterogeneous
      population, with phenotypes that change on activation or differentiation. Most of
      the monocytes express lipopolysaccharide (LPS) receptor, CD14 intensely, and do
      not express Fc gamma receptor III, CD16 (CD14++CD16- monocytes). But monocytes
      expressing CD16 with reduced CD14 (CD14+CD16+ monocytes) increase in inflammatory
      diseases as well as sepsis and bacteremia in hemodialysis patients. CD45RA is
      expressed on activated monocytes, and is regarded as an activation marker of
      peripheral blood monocytes. The purpose of this study was to determine the
      phenotypic and functional alteration of monocytes in periodontitis patients.
      METHODS: Peripheral blood was collected from 33 aggressive periodontitis patients
      (22 females, 11 males), 55 chronic periodontitis patients (35 females, 20 males)
      and 30 healthy subjects (16 females, 14 males), and the expression of CD14, CD16
      and CD45RA on monocytes was determined using flow cytometry. The production of
      interleukin-6 (IL-6) by CD16+ and CD16- monocytes stimulated with LPS from
      Escherichia coli and Actinobacillus actinomycetemcomitans was also examined using
      flow cytometry. RESULTS: The percentage of CD14+CD16+ monocytes was significantly
      increased in chronic periodontitis patients. Percentage of monocytes expressing
      CD45RA was significantly increased in aggressive periodontitis patients compared
      to healthy subjects. CD16+ and CD16- monocytes produced IL-6 in response to LPS
      from E. coli and A. actinomycetemcomitans, and the percentage of IL-6 producing
      cells was higher in CD16+ monocytes than CD16- monocytes, suggesting that
      CD14+CD16+ monocytes represent a hyper-reactive phenotype. CONCLUSIONS: The
      present study demonstrated that CD14+CD16+ monocytes and CD45RA+ monocytes were
      increased in chronic and aggressive periodontitis, respectively. These findings
      suggest that alteration of monocytes in periodontitis patients could be evaluated
      by monitoring the surface expression of CD14, CD16 and CD45RA on monocytes.

PMID- 14687233
TI  - Preventing osteoporotic fractures with antiresorptive therapy: implications of
      microarchitectural changes.
AB  - Prospective studies have demonstrated that low bone mass correlates well with
      increased risk of osteoporotic fractures at various skeletal sites. Trials have
      likewise confirmed that enhancing bone mass with antiresorptive therapy reduces
      fracture incidence in individuals at risk. However, correlation of bone mineral
      density (BMD) increases with therapeutic risk reduction has proved less
      consistent than correlation of BMD decreases with greater fracture risk in the
      untreated. Indeed, various analyses have indicated that - even during treatment
      with potent bisphosphonates like alendronate and risedronate - BMD changes from
      baseline account for <30% of the reduction in vertebral fractures in treated
      women. It is clearly, therefore, that factors other than BMD are involved in the
      reduction of fracture risk achieved by antiresorptive therapies. According to
      recent micro-computed tomography imaging and other studies, antiresorptive
      therapy can help rebuild the microarchitecture of bone as well as strengthen the
      materials that go into it. When treating individuals with osteoporosis, these
      microarchitectural changes contribute to the reduction of fracture risk achieved
      by antiresorptive therapies.

PMID- 14687234
TI  - Heart rate variability in long-term risk assessment in middle-aged women with
      coronary heart disease: The Stockholm Female Coronary Risk Study.
AB  - OBJECTIVES: Low heart rate variability (HRV) is associated with poor prognosis
      after acute coronary events in men. In women, the prognostic impact is not well
      documented. The objective of this study was to assess the long-term predictive
      power of HRV on mortality amongst middle-aged women with coronary heart disease
      (CHD). DESIGN, SETTINGS AND SUBJECTS: Consecutive women below 65 years
      hospitalized for an acute coronary syndrome during a 3-year period in Stockholm
      were examined for cardiovascular prognostic factors including HRV, and followed
      for a median of 9 years. An ambulatory 24-h electrocardiograph was recorded
      during normal activities, 3-6 months after hospitalization. SDNN index (mean of
      the standard deviations of all normal to normal intervals for all 5-min segments
      of the entire recording) and the following frequency domain parameters were
      assessed: total power, high-frequency (HF) power, low-frequency (LF) power, very
      low frequency (VLF) power and LF/HF ratio. Using Cox proportional hazards
      regression, the hazard ratios (HR) for each 25% decrease of the HRV parameters
      were assessed. RESULTS: After controlling for the independent, significant
      predictors of mortality amongst the clinical variables, the following HRV
      parameters were found to be significant predictors of all-cause mortality: SDNN
      index [HR 1.56, 95% confidence intervals (CI) 1.19-2.05], total power (HR 1.21,
      95% CI 1.08-1.35), VLF power (HR 1.22, 95% CI 1.09-1.36), LF power (HR 1.18 95%,
      CI 1.07-1.30) and HF power (HR 1.18, 95% CI 1.05-1.33). The results were
      essentially the same when cardiovascular mortality was used as end-points. The
      HRV parameters were stronger predictors of mortality in the first 5 years
      following the index event. CONCLUSION: Low HRV is a predictor of long-term
      mortality amongst middle-aged women with CHD when measured 3-6 months after
      hospitalization for an acute coronary syndrome, even after controlling for
      established clinical prognostic markers.

PMID- 14687235
TI  - Large variations in the use of oral anticoagulants in stroke patients with atrial
      fibrillation: a Swedish national perspective.
AB  - OBJECTIVES: To explore nation-wide use of anticoagulation in stroke patients with
      atrial fibrillation, in routine clinical practice in Sweden. DESIGN: Cross
      sectional cohort study. SETTING: Patients included in Riks-Stroke, the Swedish
      national quality register for stroke care, during 2001. SUBJECTS: Hospitals with
      incomplete coverage were excluded, leaving 4538 stroke patients with atrial
      fibrillation amongst 18 276 stroke patients from 75 hospitals in six health care
      regions. MAIN OUTCOME MEASURE: Treatment with oral anticoagulants. RESULTS: At
      stroke onset, the proportion of patients with atrial fibrillation and first-ever
      stroke, receiving oral anticoagulants as primary prevention was 11.0% (range 8.4
      13.5% between regions and 2.5-24.4% between hospitals). Younger age, male sex and
      diabetes at stroke onset independently predicted primary prevention with oral
      anticoagulants. The proportion of stroke patients with atrial fibrillation
      receiving oral anticoagulants as secondary prevention at discharge was 33.5%
      (range 29.9-40.6% between regions and 16.4-61.9% between hospitals). Independent
      predictors for secondary prevention were younger age, male sex and independent
      activities of daily life (ADL) function before the stroke, being discharged to
      home, being fully conscious on admission and health care region. CONCLUSION:
      There were variations between hospitals and regions that differences in age, sex,
      functional impairments and comorbidities could not fully explain. This indicates
      that evidence-based primary and secondary prevention of embolic stroke is
      insufficiently practised. Local factors seem to determine whether patients with
      atrial fibrillation gain access to optimal prevention of stroke or not.

PMID- 14687236
TI  - C-reactive protein and myocardial infarction during percutaneous coronary
      intervention.
AB  - OBJECTIVE: To evaluate the prognostic information of preprocedural C-reactive
      protein (CRP) levels in serum to predict myocardial infarction during
      percutaneous coronary interventions (PCI). DESIGN: Prospective study. SETTING:
      University hospital. PATIENTS: A total of 400 consecutive patients with normal
      serum troponin T levels (</=0.03 microg L-1) presenting with stable or unstable
      angina pectoris. INTERVENTIONS: PCI. MAIN OUTCOME MEASURES: C-reactive protein
      levels in serum measured by a high sensitive method. Myocardial infarction
      defined as a serum troponin T elevation the day after PCI to a level >0.05 microg
      L-1. RESULTS: Eighty-three patients (21%) experienced a myocardial infarction
      during PCI. The median value of CRP before the procedure was 1.83 (0.12-99.7) mg
      L-1. No difference was seen in CRP levels before PCI between patients without or
      with myocardial infarction during PCI. Multivariate analysis identified stent
      implantation (OR 2.68, 95% CI 1.18-7.28, P = 0.03), procedure time (OR 2.15, 95%
      CI 1.28-3.67, P < 0.005) and complications during the procedure (OR 3.62, 95% CI
      1.72-7.58, P < 0.001) as independent predictors of myocardial infarction during
      PCI. CONCLUSION: Increased CRP levels in serum before PCI were not associated
      with myocardial infarction during the procedure. Furthermore, patients with an
      expected long procedure and a high probability of stent implantation have an
      increased risk of developing myocardial infarction during PCI. This finding may
      be useful to help the operator to decide the antithrombotic regime before, during
      and after the procedure and the need for observation after the procedure.

PMID- 14687237
TI  - Association of the Lewis genotype with cardiovascular risk factors and
      subclinical carotid atherosclerosis: the Atherosclerosis Risk in Communities
      (ARIC) study.
AB  - OBJECTIVES: To evaluate the relationship of Lewis genotypes with major
      cardiovascular risk factors and the intima-media thickness (IMT) of carotid
      arteries. Lewis genotyping included four major mutations of the Lewis (FUT3) gene
      at nucleotide positions 59, 1067, 202 and 314. DESIGN: Two complementary
      population-based cross-sectional studies. SETTING: The Atherosclerosis Risk in
      Communities (ARIC) Study. SUBJECTS: The relationship between Lewis genotype and
      major cardiovascular risk factors was studied in 761 men and women aged 45-64
      years without known clinical atherosclerotic disease; 577 were Caucasians and 184
      were African-Americans. The association of Lewis genotype and subclinical carotid
      atherosclerosis was studied in 419 individuals with, and 819 controls without
      carotid IMT of >1.0 mm, measured by B-mode ultrasound. MAIN OUTCOME MEASURES:
      Mean values of cardiovascular risk factors by Lewis genotype. Lewis genotype
      frequencies in subclinical carotid atherosclerosis cases and controls. RESULTS:
      Individuals with Lewis genotypes consistent with lack of alpha(1,3/1,4)
      fucosyltransferase activity (i.e. Lewis-negative genotype) had statistically
      significantly lower fasting glucose, factor VIIIc, von Willebrand factor and
      diastolic blood pressure compared with their counterparts with Lewis-positive
      genotypes. The distribution of Lewis genotypes and haplotypes was not
      significantly different between individuals with carotid IMT of >1.0 mm (cases)
      and their controls. The odds of carotid atherosclerosis in carriers of the Lewis
      negative genotype was 1.23 (95% confidence interval 0.70-2.16) compared to
      individuals with Lewis-positive genotype, controlling for age, gender and
      race/ARIC field centre. CONCLUSION: The lack of a statistically significant
      association between Lewis 'genotype' and subclinical atherosclerosis in our data
      suggests that earlier studies reporting associations at the 'phenotypic' level
      may reflect aspects of the biology of the Lewis system other than an inherent
      genetic property.

PMID- 14687238
TI  - Ultrasonic backscatter of the carotid wall in young and older athletes.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of habitual
      exercise on the age-related changes of carotid wall composition defining its
      acoustic reflectivity by the quantitative approach of integrated backscatter
      (IBS) analysis. DESIGN: Cross-sectional study. SETTING: University Hospital.
      SUBJECTS: Fifty-four competitive long-distance runners (males, age range 22-72
      years) and 50 healthy sedentary controls. MAIN OUTCOME MEASURES: All the subjects
      underwent both 2-D conventional ultrasonography and IBS analysis. IBS values were
      sampled from a region of interest (ROI) placed within five consecutive regions of
      the common carotid intima-media, and then corrected (C-IBS) for the IBS value of
      the adventitia. RESULTS: Athletes showed a lower C-IBS (-27.07 +/- 2.9 dB vs. 
      24.57 +/- 4 dB, P < 0.0001) and a smaller intima-media thickness (IMT: 0.64 +/-
      0.16 mm vs. 0.78 +/- 0.21 mm, P < 0.001) respect to sedentary controls. By
      selecting the lowest (<30 years of age) and the highest (>60 years of age)
      tertile of age, we assess the influence of age on IMT and IBS. Sedentary older
      individuals exhibited an IMT higher respect to young controls and to the both
      trained subgroups (P < 0.0001). C-IBS was lower in both subgroups of athletes,
      independently of age, and lower in sedentary young people respect to sedentary
      older subgroup (P < 0.0001). Endurance chronic exercise blunted the difference of
      C-IBS observed between young and older sedentary individuals. Moreover, C-IBS was
      positively related to age (r = 0.77, P < 0.0001) and IMT (r = 0.52, P < 0.0001).
      CONCLUSIONS: The age-related changes of the arterial wall are attenuated by
      physical training. These modifications can be quantitatively discriminated by
      ultrasonic backscatter method.

PMID- 14687239
TI  - Platelet and haemorheological markers in 'high risk' hypertensives are improved
      by tighter blood pressure control and cardiovascular risk management: a substudy
      of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).
AB  - OBJECTIVE: To investigate the impact of intensified cardiovascular risk
      management on soluble markers of platelet, endothelial and rheological function
      in a population of middle-aged hypertensive patients at high risk of
      cardiovascular complications. DESIGN: Prospective follow-up study. SUBJECTS AND
      METHODS: A total of 159 hypertensive patients [138 male, mean age 64 (+/-8)
      years] and 80 healthy controls were studied. Plasma levels of soluble P-selectin
      (sP-sel, a marker of platelet function), von Willebrand factor (vWF, an index of
      endothelial damage/dysfunction) and rheological indices [fibrinogen (Fib), plasma
      viscosity (PV), haematocrit (HCT), white blood count (WBC) and platelet count]
      were measured at baseline and again (in the patients) after 6 months' treatment.
      RESULTS: As expected, 6 months of intensified cardiovascular risk management
      resulted in a significant fall in mean blood pressure (BP) and total cholesterol.
      It also resulted in reduced haematocrit, vWF, sP-sel, WBC and PV levels (all P <
      0.001), but not plasma fibrinogen. There were no correlations between the fall in
      BP and the improvement in any of the research indices. CONCLUSIONS: Intensified
      cardiovascular risk management results in significant improvements in indices of
      endothelial, platelet and rheological function in a population of hypertensives
      at high risk of cardiovascular events. These improvements appear to be
      independent of the degree of change in BP. Given the fundamental role of
      interactions between the endothelium and circulating blood components in the
      pathogenesis of hypertensive complications this may be of importance in
      preventing adverse cardiovascular outcomes.

PMID- 14687240
TI  - Effect of diet intervention on long-term mortality in healthy middle-aged men
      with combined hyperlipidaemia.
AB  - OBJECTIVES: The aim was to study the effect of a 5-year diet intervention on 24
      year mortality in middle aged men with combined hyperlipidaemia. SETTING: We
      studied 104 initially healthy men (in 1972) aged 40-49 years with baseline values
      of total serum cholesterol >6.45 mmol L-1 and fasting triglycerides >2.55 mmol L
      1, within the randomized diet and smoking cessation trial of the Oslo study (n =
      1232). METHODS: The participants were randomized to a 5-year diet intervention or
      a control group. The diet consisted of a traditional lipid-lowering diet with
      emphasis on reduction of saturated fat, total caloric intake and body weight. The
      groups were initially well balanced with regard to traditional risk factors for
      mortality. RESULTS: Thirty-three subjects died during the 24-year observation
      period [17 of cardiovascular disease (CVD) and 12 of cancer]. In the diet
      intervention group, mortality was 51% lower (RR = 0.49, 95% CI 0.22-0.91, P =
      0.022) as compared with the control group. This difference remained significant
      in a Cox regression analysis after adjusting for age and smoking status (RR =
      0.47, 95% CI 0.23-0.96, P = 0.038). CONCLUSION: This study indicates that the
      investigated 5-year diet intervention significantly reduces late mortality in
      healthy middle-aged men with combined hyperlipidaemia.

PMID- 14687241
TI  - Diurnal triglyceridaemia and insulin resistance in mildly obese subjects with
      normal fasting plasma lipids.
AB  - OBJECTIVE: A novel method has been developed to study diurnal triglyceride (TG)
      profiles using repeated capillary self-measurements in an 'out-of-hospital'
      situation. We assessed the diurnal capillary TG (TGc) profile in males with mild
      obesity and evaluated the use of plasma and capillary TG as markers of insulin
      resistance. DESIGN: Cross-sectional study. SETTING AND SUBJECTS: Fifty-four lean
      (body mass index, BMI < 25 kg m-2) and 27 mildly obese (25 < BMI < 30 kg m-2),
      normolipidaemic males measured capillary TG concentrations on six fixed time
      points over a 3-day period in an 'out-of-hospital' situation. MAIN OUTCOME
      MEASURES: The total area under the TGc curve (TGc-AUC) and incremental area under
      the TGc curve (TGc-IAUC) were used as estimation of diurnal triglyceridaemia.
      Fasting blood samples were obtained once. Food intake was recorded by all
      participants. RESULTS: Obese and lean subjects had comparable fasting capillary
      TG concentrations (1.37 +/- 0.40 mmol L-1 and 1.32 +/- 0.53 mmol L-1,
      respectively). However, during the day, obese subjects showed a greater TG
      increase, resulting in significantly higher TGc-AUC (27.1 +/- 8.4 and 23.0 +/-
      6.3 mmol h-1 l-1, respectively; P < 0.05) and TGc-IAUC (7.9 +/- 5.8 and 4.6 +/-
      6.6 mmolh-1 L-1, respectively; P < 0.05). The total group of 81 males was divided
      into quartiles based on fasting plasma TG, fasting capillary TG, TGc-AUC and TGc
      IAUC. Amongst these variables, TGc-AUC was the only significant discriminator of
      subjects with high homeostasis model assessment (HOMA) (insulin resistance)
      compared with low HOMA (insulin sensitive). Overall, BMI was the strongest
      determinant of HOMA. CONCLUSIONS: Diurnal TG profiles can be used to investigate
      postprandial lipaemia in both lean and mildly obese subjects and may help to
      detect subjects with an underlying disposition for hypertriglyceridaemia related
      to insulin resistance, i.e. the metabolic syndrome.

PMID- 14687242
TI  - IGFBP-1 levels in adult women born small for gestational age suggest insulin
      resistance in spite of normal BMI.
AB  - OBJECTIVE: Impaired fetal development may contribute to decreased insulin
      sensitivity. This study was designed to characterize serum markers of insulin
      resistance in adults born small for date or born prematurely. STUDY DESIGN: Fifty
      subjects, all women, were evaluated at a mean age +/- SD of 26 +/- 2 years
      (range: 23-30 years). They were allocated to three groups: (i) born fullterm with
      birth weight <2600 g (n = 18) (small for gestational age, SGA), (ii) born before
      gestational week 32 (n = 15) (ex-preterm), and (iii) controls, born fullterm with
      appropriate birth weight (n = 17). Anthropometric data as well as fasting serum
      samples of plasma B-glucose, serum lipids, insulin, insulin-like growth factor-I
      (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) levels were
      determined. RESULTS: In the SGA group final height was lower and they weighed
      less compared with the controls. Fasting insulin and glucose levels did not
      differ amongst the groups. Triglycerides were lower in the SGA group and in the
      ex-preterm group compared with the controls (P < 0.05). The SGA group showed
      lower IGFBP-1 levels compared with the controls median 17 (range 3-121) vs. 26 (7
      67) microg L-1; P < 0.05]. The IGF-I levels in the SGA, ex-preterm and control
      groups were 212 +/- 58, 259 +/- 37 and 216 +/- 32 microg L-1, respectively,
      corresponding to a mean SD score of -0.8 +/- 1.0, 0.1 +/- 0.6 and -0.6 +/- 0.6.
      CONCLUSION: As IGFBP-1 is a marker of insulin sensitivity, the low levels
      observed in adult women with normal BMI, born small for date, suggest relative
      insulin resistance in spite of normal BMI.

PMID- 14687243
TI  - Coffee and incidence of diabetes in Swedish women: a prospective 18-year follow
      up study.
AB  - OBJECTIVES: To examine the long-term incidence of diabetes in relation to coffee
      consumption in Swedish women. DESIGN: Prospective longitudinal cohort study.
      SETTING: City of Goteborg, Sweden. SUBJECTS: A random population sample of 1361
      women, aged 39-65 years, without prior diabetes or cardiovascular disease took
      part in a screening study in 1979-1981 with questionnaires, physical examination
      and blood sampling. MAIN OUTCOME MEASURES: The development of diabetes until 1999
      was identified by questionnaires in a second screening and the Swedish hospital
      discharge register. RESULTS: Altogether, there were 74 new cases of diabetes. The
      risk of developing diabetes was 475 per 100 000 person-years in women who
      consumed two cups of coffee or less per day, 271 in women who consumed three to
      four cups per day, 202 with a consumption of five to six cups per day, and 267 in
      drinkers of seven cups or more per day. Associated hazard ratios, after
      adjustment for age, smoking, low physical activity, education and body mass index
      were 0.55 (0.32-0.95), 0.39 (0.20-0.77) and 0.48 (0.22-1.06) for daily
      consumption of three to four, five to six and seven cups or more, respectively,
      with a consumption of less than two per day as reference. Additional adjustment
      for serum cholesterol and triglycerides attenuated the relation between coffee
      and diabetes slightly, indicating a possible mediating effect on the effect of
      coffee by serum lipids. CONCLUSIONS: The findings of the present study support
      the hypothesis that coffee consumption protects from the development of diabetes
      in women.

PMID- 14687244
TI  - Diabetes control in Swedish community dwelling elderly: more often tight than
      poor.
AB  - OBJECTIVE: To determine glycaemic control in elderly patients with diabetes
      living in community dwelling. DESIGN: Descriptive, cross-sectional and open.
      Prospective with regard to blood glucose. SETTING: Community-dwelling in
      patients. SUBJECTS: From a total number of 351 patients in seven Swedish centres
      of community dwelling we identified and recruited all 45 patients with diabetes
      receiving treatment with insulin, and/or oral medication. MAIN OUTCOME MEASURES:
      Blood glucose was measured fasting, 2 h after breakfast, in the evening and at
      night, for three consecutive days. RESULTS: Mean HbA1c was 5.9 +/- 1.1% (range
      3.6-8.6%). The patients were split in three HbA1c-groups for analysis: lower-
      (3.6-5.3%), middle- (5.4-6.3%) and higher-tertile (6.4-8.6%). The groups where
      similar with regard to age, time in community dwelling, ability to eat and move
      around independently, but body mass index was lower in the lower tertile (P <
      0.003 and P < 0.04, compared with middle- and higher-tertiles). We recorded 14
      episodes with blood glucose </=4.0 mmol L-1 in eight patients. Blood glucose
      </=4.0 mmol L-1 was mostly recorded during night (n = 8) or in the morning (n =
      3). CONCLUSIONS: Swedish patients with diabetes in community dwelling are over-
      rather than under-treated and have low HbA1c levels. Despite very regular eating
      habits and near total compliance with medication, hypoglycaemias are frequent and
      possibly linked to malnutrition.

PMID- 14687245
TI  - The influence of smoking and smokeless tobacco use on weight amongst men.
AB  - OBJECTIVE: To explore the effect of tobacco use (smoking and smokeless tobacco)
      and cessation on body weight. DESIGN: Cross-sectional and prospective follow-up
      study. SETTING: Northern Sweden. SUBJECTS: A total of 2993 men aged 25-64 years
      who participated in the northern Sweden MONICA study in 1986, 1990 or 1994, 1650
      of whom were followed up in 1999. MAIN OUTCOME MEASURES: The prevalence of
      overweight [body mass index (BMI) >/= 27] amongst tobacco users was compared with
      nonusers at entry into the study. The average annual percentage weight gain
      amongst men was also determined according to tobacco use both at entry and at
      follow-up, and the development of overweight amongst tobacco-use groups was
      reported using standardized incidence ratios. RESULTS: Smokers who quit tobacco
      during the follow-up period gained significantly more weight than smokers who
      switched to snus (annual gain 0.96% vs. 0.51%, P < 0.05). At entry, ex-smokers
      had higher prevalence of overweight than nonusers of tobacco [prevalence ratio
      (PR) = 1.24, 95% confidence interval (CI) = 1.10-1.40]. Snus users had slightly
      higher prevalence of overweight at entry (PR = 1.20, CI = 1.01-1.42). Snus users
      who quit gained more weight than nonusers (0.70% vs. 0.44%, P < 0.05) or those
      who continued to use snus (0.42%). CONCLUSIONS: Cessation of tobacco, either
      cigarettes or snus, leads to significantly increased weight gain. However, snus
      use may play a role in lowering the weight gain following smoking cessation.

PMID- 14687246
TI  - Parathyroid surgery is associated with a decreased risk of hip and upper arm
      fractures in primary hyperparathyroidism: a controlled cohort study.
AB  - OBJECTIVES: To study if parathyroid surgery reduced fracture risk in patients
      with primary hyperparathyroidism. DESIGN: Controlled cohort study. SETTING: All
      subjects diagnosed with primary hyperparathyroidism (ICD8 codes: 252.00, 252.01,
      252.03, 252.04, 252.05, 252.08, 252.09, and ICD10 codes: E21.0, E21.2, E21.3)
      between 1980 and 1999 in Denmark were retrieved from the National Hospital
      Discharge System. SUBJECTS: A total of 3213 subjects (mean age at diagnosis 60.9
      +/- 16.3 years) were identified of whom 1934 (60%) had parathyroid surgery whilst
      1279 (40%) did not. Total follow-up time after diagnosis was 19.565 (median 6.1)
      years. MAIN OUTCOME MEASURE: Fracture occurrence after diagnosis was identified
      from the National Hospital Discharge System. RESULTS: Conservatively treated
      patients were older than surgically treated at diagnosis (64.2 +/- 17.4 years vs.
      58.3 +/- 15.2 years, P < 0.01). The mean serum calcium was 2.95 mmol L-1 in
      surgically treated and 2.74 in conservatively treated in a subgroup from one
      centre, n = 687). At the time of diagnosis, 172 (9%) of the subsequently
      surgically treated had had any fracture whilst the same was the case for 176
      (14%) of the conservatively treated (P < 0.05). Parathyroid surgery reduced the
      risk of hip (HR = 0.44, 95% CI: 0.32-0.62) and upper arm (HR = 0.44, 95% CI: 0.27
      0.72) fractures after diagnosis whilst the occurrence of other fracture types
      remained unchanged. CONCLUSIONS: Parathyroid surgery reduces the occurrence of
      hip and upper arm fractures with approximately 50% in patients with primary
      hyperparathyroidism. This may advocate surgery in patients with primary
      hyperparathyroidism with serum calcium levels in the range presented here.
      Further studies in patients with mild disease are warranted.

PMID- 14687247
TI  - Skeletal muscle and nutritional assessment in chronic renal failure patients on a
      protein-restricted diet.
AB  - BACKGROUND: The close relationship between protein-energy malnutrition and
      quality of life, morbidity and mortality, makes mandatory a careful evaluation of
      the nutritional status and muscle mass in chronic renal failure (CRF) patients.
      METHODS: Nutritional and skeletal muscle data were obtained from 28 nondiabetic
      patients with severe CRF (glomerular filtration rate, GFR < 15 mL min-1) on
      conservative treatment. Of them, 14 (8 males, 4 females) were on a conventional
      low-protein (0.6 g kg-1 body weight) diet (LPD) and 14 (8 males, 4 females) were
      on a very low-protein (0.3 g kg-1 body weight) diet supplemented with essential
      amino acids and ketoacids (Ketodiet); 28 healthy sex- and age-matched subjects
      served as controls. We evaluated biochemistry, anthropometry, bioelectrical
      impedance vector analysis, and three noninvasive tests investigating some
      skeletal muscle features: (a) myoelectrical fatigue phenomenon was studied using
      a surface electromyography technique that provides data on conduction velocity
      (CV), median frequency of power spectrum (MDF) and average rectified value (ARV)
      of myofibre action potential, at 15 and 35 Hz stimulation frequency; (b) muscle
      oxidative metabolism was studied by serum lactate following aerobic exercise; and
      (c) muscle strength of the legs was studied using an isokinetic exercise test at
      two different angular velocities (60 degrees and 180 degrees s-1). RESULTS: No
      difference between patients and controls was detected regarding CV, MDF and ARV,
      at 35 and 15 Hz testing. Serum lactate was higher in patients than in controls at
      1, 5, 10 and 30 min recovery. A decreased knee extension and flexion strength was
      detected in CRF patients both at low (60 degrees s-1) and at high (180 degrees s
      1) angular velocity; muscle strength deficit negatively correlated to serum
      albumin (r = -0.52, P < 0.01), but no relationship was found with protein intake
      or residual renal function. No difference was found between LPD and Ketodiet
      patients regarding the studied muscular tests as well as the anthropometry and
      bio-impedance data. CONCLUSIONS: Implementation of a proper dietary regimen,
      including severe restriction of protein intake can preserve lean body mass and
      nutritional status of advanced CRF patients. Skeletal muscle shows unchanged
      sarcolemma excitability but abnormal oxidative metabolism and reduced segmental
      strength. Regular physical activity and a close clinical and dietary monitoring
      should be recommended for the predialysis patient care.

PMID- 14687248
TI  - Beta-lactamase inhibitor enhances Helicobacter pylori eradication rate.
AB  - OBJECTIVES: One-week triple therapy, a combination of acid suppression with two
      antibiotics, is the gold standard for anti-Helicobacter pylori treatment. There
      is increasing evidence of H. pylori resistance to classical triple therapy.
      Recently, it was reported that the amoxicillin-clavulanate combination had a
      slightly higher activity than amoxicillin alone against H. pylori, and that beta
      lactamase inhibitors had 'in-vitro' antibacterial activity against H. pylori.
      SETTING: To evaluate the efficacy of 1 week triple therapy omeprazole,
      clarithromycin and amoxicillin plus clavulanate compared with omeprazole,
      clarithromycin and amoxicillin for H. pylori eradication. The study was open
      randomized. SUBJECTS: Sixty dyspeptic patients (36 male, 24 female; mean age 53
      +/- 9 years) with Helicobacter pylori infection never treated before, were
      enrolled and randomly assigned to two different 7-day triple therapies: (i) (n =
      30) amoxicillin 875 mg plus clavulanic acid 125 mg b.i.d., clarithromycin 500 mg
      b.i.d., omeprazole 20 mg b.i.d. (ACCO); (ii) (n = 30) amoxicillin 1 g b.i.d.,
      clarithromycin 500 mg b.i.d., omeprazole 20 mg b.i.d. (ACO). Bacterial
      eradication was assessed by 13C-urea breath test 4-6 weeks after therapy.
      Information on gastrointestinal symptoms and antibiotic-related side-effects were
      recorded using a questionnaire. RESULTS: All patients completed the study. A
      significantly higher H. pylori eradication rate with ACCO compared with ACO:
      (26/30) 86.6 vs. (20/30) 66.6%, respectively (P < 0.05) were observed. No major
      side-effects were reported, whilst 8% patients complained of mild side-effects;
      no significant differences were noted between the two groups. CONCLUSIONS: Our
      results suggest that amoxicillin and clavulanate in combination achieve a higher
      H. pylori eradication rate than amoxicillin alone, without any increase in side
      effects. The combination of amoxicillin and clavulanate may represent an
      alternative therapeutic scheme for the treatment of H. pylori infection.

PMID- 14687249
TI  - Severe hypoplasia of the abdominal aorta and its branches in a patient and his
      daughter.
AB  - We report the history of a patient and his daughter, both affected with
      hypoplasia of the abdominal aorta and its branches, leading to early and dramatic
      complications. In the index patient, renal ischaemia as a result of severe
      hypoplasia of the abdominal aorta and the origin of renal arteries led to
      progressive renal failure and end-stage renal disease at the age of 32 years.
      Other vascular abnormalities included hypoplasia of the celiac trunk (CT) and
      superior mesenteric artery (SMA). After a successful kidney transplantation at
      the age of 40 years, he eventually deceased following an episode of possibly
      ischaemic acute pancreatitis at 47 years. The patient's daughter suffered from an
      haemorrhagic stroke at the age of 7 years, which led to the discovery of severe
      hypertension caused by bilateral narrowing of renal arteries, as well as
      hypoplasia of CT, SMA, subclavian and pulmonary arteries. Biopsy of the narrowed
      renal artery of the daughter showed a particular form of fibrodysplasia
      characterized by an unusual fibrosis of the inner part of the media, just beneath
      the internal elastic lamina. To our knowledge, this is the first report of
      familial hypoplasia of the abdominal aorta. It might be the cardinal
      manifestation of a familial form of fibromuscular dysplasia (FMD). Interestingly,
      the histological lesions described in the daughter's renal artery differ from the
      classical form of medial FMD.

PMID- 14687250
TI  - A cardiac sodium channel mutation identified in Brugada syndrome associated with
      atrial standstill.
AB  - Mutations in the cardiac Na+ channel gene SCN5A are responsible for multiple
      lethal ventricular arrhythmias including Brugada syndrome and congenital long QT
      syndrome. Here we report a case of Brugada syndrome with ST elevation in the
      right precordial and inferior leads accompanied by atrial standstill and
      spontaneous ventricular fibrillation. Atrial standstill and J wave elevation were
      provoked by procainamide. Genetic analysis revealed a missense mutation (R367H)
      in SCN5A. The resultant mutant Na+ channel was nonfunctional when expressed
      heterologously in Xenopus oocytes. Our study suggests that genetic defects in
      SCN5A may be associated with atrial standstill in combination with ventricular
      arrhythmias.

PMID- 14687251
TI  - Family with autosomal dominant hyperinsulinism associated with A456V mutation in
      the glucokinase gene.

PMID- 14687252
TI  - Lack of association of the Gly972Arg mutation of the insulin receptor substrate-1
      gene with coronary artery disease in the Austrian population.

PMID- 14687254
TI  - Effects of computerized guidelines for managing heart disease in primary care.
AB  - BACKGROUND: Electronic information systems have been proposed as one means to
      reduce medical errors of commission (doing the wrong thing) and omission (not
      providing indicated care). OBJECTIVE: To assess the effects of computer-based
      cardiac care suggestions. DESIGN: A randomized, controlled trial targeting
      primary care physicians and pharmacists. SUBJECTS: A total of 706 outpatients
      with heart failure and/or ischemic heart disease. INTERVENTIONS: Evidence-based
      cardiac care suggestions, approved by a panel of local cardiologists and general
      internists, were displayed to physicians and pharmacists as they cared for
      enrolled patients. MEASUREMENTS: Adherence with the care suggestions, generic and
      condition-specific quality of life, acute exacerbations of their cardiac disease,
      medication compliance, health care costs, satisfaction with care, and physicians'
      attitudes toward guidelines. RESULTS: Subjects were followed for 1 year during
      which they made 3,419 primary care visits and were eligible for 2,609 separate
      cardiac care suggestions. The intervention had no effect on physicians' adherence
      to the care suggestions (23% for intervention patients vs 22% for controls).
      There were no intervention-control differences in quality of life, medication
      compliance, health care utilization, costs, or satisfaction with care. Physicians
      viewed guidelines as providing helpful information but constraining their
      practice and not helpful in making decisions for individual patients.
      CONCLUSIONS: Care suggestions generated by a sophisticated electronic medical
      record system failed to improve adherence to accepted practice guidelines or
      outcomes for patients with heart disease. Future studies must weigh the benefits
      and costs of different (and perhaps more Draconian) methods of affecting
      clinician behavior.

PMID- 14687255
TI  - Misperceptions about beta-blockers and diuretics: a national survey of primary
      care physicians.
AB  - BACKGROUND: Based on a series of clinical trials showing no difference in the
      effectiveness or tolerability of most major classes of antihypertensive
      medications, the Joint National Commission on High Blood Pressure Treatment
      recommends that physicians prescribe beta-blockers or diuretics as initial
      hypertensive therapy unless there are compelling indications for another type of
      medication. Nevertheless, many physicians continue to favor more expensive
      medications like angiotensin-converting enzyme (ACE) inhibitors and calcium
      channel blockers as first line agents. The persistent use of these agents raises
      questions as to whether physicians perceive ACE inhibitors and calcium channel
      blockers to be better than beta-blockers and diuretics. METHODS: We surveyed
      1,200 primary care physicians in 1997, and another 500 primary care physicians in
      2000, and asked them to estimate the relative effectiveness and side effects of 4
      classes of medication in treating a hypothetical patient with uncomplicated
      hypertension: ACE inhibitors, beta-blockers, calcium channel blockers, and
      diuretics. In addition, we asked them to indicate whether they ever provided free
      samples of hypertension medications to their patients. RESULTS: Perceptions of
      the relative effectiveness and side effects of the 4 classes of hypertension
      medications did not significantly change over the 3 years, nor did prescription
      recommendations. Physicians perceive that diuretics are less effective at
      lowering blood pressure than the other 3 classes (P <.001). They also perceive
      that beta-blockers are less tolerated than the other 3 classes (P <.001). In a
      multivariate model, perceptions of effectiveness and tolerability displayed
      significant associations with prescription preference independent of background
      variables. The only other variable to contribute significantly to the model was
      provision of free medication samples to patients. CONCLUSIONS: Despite numerous
      clinical trials showing no difference in the effectiveness or side-effect
      profiles of these 4 classes of drugs, most physicians believed that diuretics
      were less effective and beta-blockers were less tolerated than other medications.
      Moreover, their prescription practices were associated with their provision of
      free samples provided by pharmaceutical representatives, even after adjusting for
      other demographic characteristics. Efforts to increase physicians' prescribing of
      beta-blockers and diuretics may need to be directed at overcoming
      misunderstandings about the effectiveness and tolerability of these medicines.

PMID- 14687256
TI  - Development and validation of the hyperlipidemia: attitudes and beliefs in
      treatment (HABIT) survey for physicians.
AB  - INTRODUCTION: Many patients treated with lipid-lowering medications in clinical
      practice do not achieve targeted National Cholesterol Education Program (NCEP)
      goals for low-density lipoprotein cholesterol (LDL-C), despite the proven
      efficacy of these medications. Understanding physician attitudes and beliefs
      about treating patients to goal may be useful in improving patient care and
      ensuring that all patients receive the benefits of treatments shown to be optimal
      in clinical trials. OBJECTIVE: To develop a theoretically based, and
      statistically reliable and valid survey instrument for measuring the attitudes
      and beliefs of physicians toward hyperlipidemia and its treatment, including
      treatment of patients to goal. To determine whether the attitudes measured were
      associated with physician intentions to treat patients to LDL-C goal. METHODS: We
      assessed the reliability of the instrument through an examination of the internal
      consistency and factor structure of the constructs. Validity was assessed through
      zero-order correlations among the constructs and the relationship between the
      constructs and an intent to treat to goal case study. RESULTS: Internal
      consistency scores for the 8 constructs ranged from 0.48 to 0.75. Factor loadings
      indicated that the individual items belonged to their respective constructs, as
      hypothesized. The predictive validity of the instrument was demonstrated by
      significant relationships between 5 of the 8 attitudinal constructs and an intent
      to treat to goal case study. CONCLUSIONS: The HABIT physician survey is the first
      validated instrument covering a broad set of attitudes about the treatment of
      hyperlipidemia that are both theoretically and empirically linked to physician
      intent to treat to NCEP LDL-C goal.

PMID- 14687257
TI  - Primary care patients with depression are less accepting of treatment than those
      seen by mental health specialists.
AB  - OBJECTIVE: This study examined whether depressed patients treated exclusively in
      primary care report less need for care and less acceptability of treatment
      options than those depressed patients treated in the specialty mental health
      setting after up to 6 months of treatment. DESIGN: Cross-sectional study.
      SETTING: Forty-five community primary care practices. PARTICIPANTS: A total of
      881 persons with major depression who had received mental health services in the
      previous 6 months and who enrolled in 3 of the 4 Quality Improvement for
      Depression Collaboration Studies. MEASUREMENTS AND RESULTS: Patients were
      categorized into 1 of 2 groups: 1) having received mental health services
      exclusively from a primary care provider (45%), or 2) having received any
      services from a mental health specialist (55%) in the previous 6 months. Compared
      with patients who received care from mental health specialists, patients who
      received mental health services exclusively from primary care providers had 2.7
      fold the odds (95% confidence interval [CI], 1.6 to 4.4) of reporting that no
      treatment was definitely acceptable and had 2.4-fold the odds (95% CI, 1.5 to
      3.9) of reporting that evidence-based treatment options (antidepressant
      medication) were definitely not acceptable. These results were adjusted for
      demographic, social/behavioral, depression severity, and economic factors using
      multiple logistic regression analysis. CONCLUSIONS: Patients with depression
      treated exclusively by primary care providers have attitudes and beliefs more
      averse to care than those seen by mental health specialists. These differences in
      attitudes and beliefs may contribute to lower quality depression care observed in
      comparisons of primary care and specialty mental health providers.

PMID- 14687258
TI  - Do depressed older adults who attribute depression to "old age" believe it is
      important to seek care?
AB  - OBJECTIVE: To determine whether depressed older adults who attribute becoming
      depressed to "old age" rather than illness are more likely to believe it is not
      important to seek treatment for depression. DESIGN: Cross-sectional mailed
      survey. SETTING: Academically affiliated primary care physicians' network.
      PARTICIPANTS: Surveys were mailed to 588 patients age > or =65 years who were
      randomly identified from patient lists of 20 physicians. Surveys were returned by
      429 patients (73%). Patients were eligible for this study if they scored > or =2
      points on the 5-item Geriatric Depression Scale (n = 94) and were not missing key
      variables (final n = 90). MEASUREMENTS AND MAIN RESULTS: Of the 90 depressed
      patients, 48 (53%) believed that feeling depressed was very important to discuss
      with a doctor. In unadjusted analysis, older adults who did not believe it is
      very important to discuss feeling depressed with a doctor were more likely to
      attribute becoming depressed to aging (41% vs 17%; P =.012). In a logistic
      regression model adjusting for sociodemographic characteristics, number of
      impairments in basic and instrumental activities of daily living, medical
      comorbidity, and physical (PCS-12) and mental (MCS-12) component summary scores
      from the Medical Outcomes Study Short-Form-12, depressed older adults who
      attributed depression to aging had a 4.3 times greater odds than those who
      attributed depression to illness to not believe it is very important to discuss
      depression with a doctor (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.3
      to 14.5). CONCLUSIONS: Among older persons with depression, attributing feeling
      depressed to old age may be an important barrier to care seeking.

PMID- 14687259
TI  - Patient and caregiver characteristics associated with depression in caregivers of
      patients with dementia.
AB  - OBJECTIVE: Many patients with dementia who live at home would require nursing
      home care if they did not have the assistance of family caregivers. However,
      caregiving sometimes has adverse health consequences for caregivers, including
      very high rates of depression. The goal of this study was to determine the
      patient and caregiver characteristics associated with depression among caregivers
      of patients with dementia. DESIGN: Cross-sectional study. PARTICIPANTS AND
      SETTING: Five thousand six hundred and twenty-seven patients with moderate to
      advanced dementia and their primary caregivers upon enrollment in the Medicare
      Alzheimer's Disease Demonstration (MADDE) at 8 locations in the United States.
      MEASUREMENTS: Caregiver depression was defined as 6 or more symptoms on the 15
      item Geriatric Depression Scale. Patient characteristics measured included
      ethnicity and other demographic characteristics, income, activities of daily
      living (ADL) function, Mini-Mental Status Exam (MMSE) score, and behavioral
      problems. Caregiver characteristics measured included demographic
      characteristics, relationship to the patient, hours spent caregiving, and ADL and
      Instrumental Activities of Daily Living (IADL) function. We used chi2 and t tests
      to measure the bivariate relationships between patient and caregiver predictors
      and caregiver depression. We used logistic regression to determine the
      independent predictors of caregiver depression. RESULTS: Thirty-two percent of
      caregivers reported 6 or more symptoms of depression and were classified as
      depressed. Independent patient predictors of caregiver depression included
      younger age (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.33 to 2.76 in
      patients less than 65 years compared to patients over 85 years), white (OR, 1.53;
      95% CI, 1.18 to 1.99) and Hispanic ethnicity (OR, 2.50; 95% CI, 1.69 to 3.70)
      compared to black ethnicity, education (OR, 1.16; 95% CI, 1.01 to 1.33 for those
      with less than a high school education), ADL dependence (OR, 1.55; 95% CI, 1.26
      to 1.90 for patients dependent in 2 or more ADL compared to patients dependent in
      no ADL), and behavioral disturbance, particularly angry or aggressive behavior
      (OR, 1.47; 95% CI, 1.27 to 1.69 for patients with angry or aggressive behavior).
      Independent caregiver predictors of depression included low income (OR, 1.45; 95%
      CI, 1.18 to 1.77 for less than 10,000 dollars/per year, compared to >20,000
      dollars per year), the relationship to the patient (OR, 2.73; 95% CI, 1.31 to
      5.72 for wife, compared to son of male patient), hours spent caregiving (OR,
      1.89; 95% CI, 1.51 to 2.38 for 40 to 79 hours/week compared to less than 40
      hours/week), and functional dependence (OR, 2.53; 95% CI, 2.13 to 3.01 for ADL
      dependent compared to IADL independent). CONCLUSION: Caregiver depression is a
      complex process, influenced by ethnicity as well as diverse patient and caregiver
      characteristics. Efforts to identify and treat caregiver depression will need to
      be multidisciplinary and focus on multiple risk factors simultaneously.

PMID- 14687260
TI  - The disavowed curriculum: understanding student's reasoning in professionally
      challenging situations.
AB  - CONTEXT: Understanding students' perceptions of and responses to lapses in
      professionalism is important to shaping students' professional development.
      OBJECTIVE: Utilize realistic, standardized professional dilemmas to obtain
      insight into students' reasoning and motivations in "real time." DESIGN:
      Qualitative study using 5 videotaped scenarios (each depicting a student placed
      in a situation which requires action in response to a professional dilemma) and
      individual interviews, in which students were questioned about what they would do
      next and why. SETTING: University of Toronto. PARTICIPANTS: Eighteen fourth-year
      medical students; participation voluntary and anonymous. MAIN OUTCOME MEASURE: A
      model to explain students' reasoning in the face of professional dilemmas.
      RESULTS: Grounded theory analysis of interview transcripts revealed that students
      were motivated to consider specific actions by referencing a Principle (an
      abstract or idealized concept), an Affect (a feeling or emotion), or an
      Implication (a potential consequence of suggested actions). Principles were
      classified as "avowed" as ideals of our profession (e.g., honesty or disclosure),
      or "unavowed" (unacknowledged or undeclared, e.g., obedience or allegiance).
      Implications could also be avowed (e.g., concerning patients) or unavowed (e.g.,
      concerning others); but students were predominantly motivated by considering
      "disavowed" implications: those pertaining to themselves (e.g., concern for
      grades, evaluations, or reputation), which are actively denied by the profession
      and discouraged as being inconsistent with altruism. CONCLUSIONS: This "disavowed
      curriculum" has implications for education, feedback, and evaluation. Instead of
      denying their existence, we should teach students how to negotiate and balance
      these unavowed and disavowed implications and principles, in order to help them
      develop their own professional stance.

PMID- 14687261
TI  - A new curriculum using active learning methods and standardized patients to train
      residents in smoking cessation.
AB  - Physicians can play a key role in smoking cessation but often fail to advise
      smokers effectively, mainly because they lack counseling skills. We need
      effective training programs starting during residency to improve physicians'
      smoking cessation interventions and smokers' quit rates. To achieve this goal, we
      developed a curriculum using active learning methods and the stages-of-change
      model. A randomized trial demonstrated that this program increased the quality of
      physician's counseling and smokers' quit rates at 1 year. This paper describes
      the educational content and methods of this program. Participants learn to assess
      smokers' stage of change, to use counseling strategies matching the smoker's
      stage, and to prescribe pharmacological therapy. This 2 half-day training program
      includes observation of video-clips, interactive workshops, role plays, practice
      with standardized patients, and written material for physicians and patients.
      Participants reached learning objectives and appreciated the content and active
      methods of the program.

PMID- 14687262
TI  - Racial and ethnic disparities in cancer screening: the importance of foreign
      birth as a barrier to care.
AB  - CONTEXT: Racial/ethnic groups comprised largely of foreign-born individuals have
      lower rates of cancer screening than white Americans. Little is known about
      whether these disparities are related primarily to their race/ethnicity or
      birthplace. OBJECTIVE: To determine whether foreign birthplace explains some
      racial/ethnic disparities in cancer screening. DESIGN, SETTING, AND SUBJECTS:
      Cross-sectional study using 1998 data from the National Health Interview Survey.
      MAIN OUTCOME MEASURES: Completion of cervical, breast, or colorectal cancer
      screening. RESULTS: Of respondents, 15% were foreign born. In analyses adjusted
      for sociodemographic characteristics and illness burden, black respondents were
      as or more likely to report cancer screening than white respondents; however,
      Hispanic and Asian-American and Pacific Islander (AAPI) respondents were
      significantly less likely to report screening for most cancers. When
      race/ethnicity and birthplace were considered together, U.S.-born Hispanic and
      AAPI respondents were as likely to report cancer screening as U.S.-born whites;
      however, foreign-born white (adjusted odds ratio [AOR], 0.58; 95% confidence
      interval [CI], 0.41 to 0.82), Hispanic (AOR, 0.65; 95% CI, 0.53 to 0.79), and
      AAPI respondents (AOR, 0.28; 95% CI, 0.19 to 0.39) were less likely than U.S.
      born whites to report Pap smears. Foreign-born Hispanic and AAPI respondents were
      also less likely to report fecal occult blood testing (FOBT); AORs, 0.72; 95% CI,
      0.53 to 0.98; and 0.61; 95% CI, 0.39 to 0.96, respectively); and sigmoidoscopy
      (AORs, 0.70; 95% CI, 0.51 to 0.97; and 0.63; 95% CI, 0.40 to 0.99, respectively).
      Furthermore, foreign-born AAPI respondents were less likely to report mammography
      (AOR, 0.49; 95% CI, 0.28 to 0.86). Adjusting for access to care partially
      attenuated disparities among foreign-born respondents. CONCLUSION: Foreign
      birthplace may explain some disparities previously attributed to race or
      ethnicity, and is an important barrier to cancer screening, even after adjustment
      for other factors. Increasing access to health care may improve disparities among
      foreign-born persons to some degree, but further study is needed to understand
      other barriers to screening among the foreign-born.

PMID- 14687263
TI  - A shortened instrument for literacy screening.
AB  - The Rapid Estimate of Adult Literacy in Medicine (REALM-R), a new 8-item
      instrument designed to rapidly screen patients for potential health literacy
      problems, was administered to 157 patients. The REALM-R was correlated with Wide
      Range Achievement Test-Revised (WRAT-R) (.64) and demonstrated a Cronbach's alpha
      of 0.91. The REALM-R identified 26 of 30 persons scoring more than 1 standard
      deviation below the mean on the WRAT-R, corresponding to a sixth grade reading
      level. The REALM-R identified a substantial number of people who scored poorly on
      the WRAT-R, and depending on further studies of validity and reliability, may
      offer a practical approach to identify patients at risk for health literacy
      problems in a clinical setting.

PMID- 14687264
TI  - Framingham-based tools to calculate the global risk of coronary heart disease: a
      systematic review of tools for clinicians.
AB  - PURPOSE: To examine the features of available Framingham-based risk calculation
      tools and review their accuracy and feasibility in clinical practice. DATA
      SOURCES: medline, 1966-April 2003, and the google search engine on the Internet.
      TOOL AND STUDY SELECTION: We included risk calculation tools that used the
      Framingham risk equations to generate a global coronary heart disease (CHD) risk.
      To determine tool accuracy, we reviewed all articles that compared the
      performance of various Framingham-based risk tools to that of the continuous
      Framingham risk equations. To determine the feasibility of tool use in clinical
      practice, we reviewed articles on the availability of the risk factor information
      required for risk calculation, subjective preference for 1 risk calculator over
      another, or subjective ease of use. DATA EXTRACTION: Two reviewers independently
      reviewed the results of the literature search, all websites, and abstracted all
      articles for relevant information. DATA SYNTHESIS: Multiple CHD risk calculation
      tools are available, including risk charts and computerized calculators for
      personal digital assistants, personal computers, and web-based use. Most are easy
      to use and available without cost. They require information on age, smoking
      status, blood pressure, total and HDL cholesterol, and the presence or absence of
      diabetes. Compared to the full Framingham equations, accuracy for identifying
      patients at increased risk was generally quite high. Data on the feasibility of
      tool use was limited. CONCLUSIONS: Several easy-to-use tools are available for
      estimating patients' CHD risk. Use of such tools could facilitate better decision
      making about interventions for primary prevention of CHD, but further research
      about their actual effect on clinical practice and patient outcomes is required.

PMID- 14687265
TI  - Motivating and helping smokers to stop smoking.
AB  - Smokers try to quit only once every 2 to 3 years and most do not use proven
      treatments. Repeated, brief, diplomatic advice increases quit rates. Such advice
      should include a clear request to quit, reinforcing personal risks of smoking and
      their reversibility, offering solutions to barriers to quitting, and offering
      treatment. All smokers should be encouraged to use both medications and
      counseling. Scientifically proven, first-line medications are nicotine gum,
      inhaler, lozenge, and patch plus the nonnicotine medication bupropion. Proven
      second-line medications are clonidine, nicotine nasal spray, and nortriptyline.
      These medications are equally effective and safe and the incidence of dependence
      is very small. The proven psychosocial therapies are behavioral and supportive
      therapies. These are as effective as medications and are effective via individual
      counseling, group, and telephone formats. The writing of this article was
      supported in part by Senior Scientist Award DA-00450 from the National Institute
      on Drug Abuse.

PMID- 14687266
TI  - Depression in caregivers of patients with dementia: a greater role for
      physicians.

PMID- 14687267
TI  - Understanding and modifying physician behavior for prevention and management of
      cardiovascular disease.

PMID- 14687272
TI  - A randomized trial of three videos that differ in the framing of information
      about mammography in women 40 to 49 years old.
AB  - OBJECTIVE: To assess the effect of providing structured information about the
      benefits and harms of mammography in differing frames on women's perceptions of
      screening. DESIGN: Randomized control trial. SETTING: General internal medicine
      academic practice. PARTICIPANTS: One hundred seventy-nine women aged 35 through
      49. INTERVENTION: Women received 1 of 3 5-minute videos about the benefits and
      harms of screening mammography in women aged 40 to 49. These videos differed only
      in the way the probabilities of potential outcomes were framed (positive,
      neutral, or negative). MEASUREMENTS AND MAIN RESULTS: We measured the change in
      accurate responses to questions about potential benefits and harms of
      mammography, and the change in the proportion of participants who perceived that
      the benefits of mammography were more important than the harms. Before seeing the
      videos, women's knowledge about the benefits and harms of mammography was
      inaccurate (82% responded incorrectly to all 3 knowledge questions). After seeing
      the videos, the proportion that answered correctly increased by 52%, 43%, and 30%
      for the 3 knowledge questions, respectively, but there were no differences
      between video frames. At baseline, most women thought the benefits of mammography
      outweighed the harms (79% positive frame, 80% neutral frame, and 85% negative
      frame). After the videos, these proportions were similar among the 3 groups (84%,
      81%, 83%, P =.93). CONCLUSIONS: Women improved the accuracy of their responses to
      questions about the benefits and harms of mammography after seeing the videos,
      but this change was not affected by the framing of information. Women strongly
      perceived that the benefits of mammography outweighed the harms, and providing
      accurate information had no effect on these perceptions, regardless of how it was
      framed.

PMID- 14687273
TI  - A randomized comparison of patients' understanding of number needed to treat and
      other common risk reduction formats.
AB  - BACKGROUND: Commentators have suggested that patients may understand quantitative
      information about treatment benefits better when they are presented as numbers
      needed to treat (NNT) rather than as absolute or relative risk reductions.
      OBJECTIVE: To determine whether NNT helps patients interpret treatment benefits
      better than absolute risk reduction (ARR), relative risk reduction (RRR), or a
      combination of all three of these risk reduction presentations (COMBO). DESIGN:
      Randomized cross-sectional survey. SETTING: University internal medicine clinic.
      PATIENTS: Three hundred fifty-seven men and women, ages 50 to 80, who presented
      for health care. INTERVENTIONS: Subjects were given written information about the
      baseline risk of a hypothetical "disease Y" and were asked (1) to compare the
      benefits of two drug treatments for disease Y, stating which provided more
      benefit; and (2) to calculate the effect of one of those drug treatments on a
      given baseline risk of disease. Risk information was presented to each subject in
      one of four randomly allocated risk formats: NNT, ARR, RRR, or COMBO. MAIN
      RESULTS: When asked to state which of two treatments provided more benefit,
      subjects who received the RRR format responded correctly most often (60% correct
      vs 43% for COMBO, 42% for ARR, and 30% for NNT, P =.001). Most subjects were
      unable to calculate the effect of drug treatment on the given baseline risk of
      disease, although subjects receiving the RRR and ARR formats responded correctly
      more often (21% and 17% compared to 7% for COMBO and 6% for NNT, P =.004).
      CONCLUSION: Patients are best able to interpret the benefits of treatment when
      they are presented in an RRR format with a given baseline risk of disease. ARR
      also is easily interpreted. NNT is often misinterpreted by patients and should
      not be used alone to communicate risk to patients.

PMID- 14687274
TI  - When do patients and their physicians agree on diabetes treatment goals and
      strategies, and what difference does it make?
AB  - BACKGROUND: For patients with chronic illnesses, it is hypothesized that
      effective patient-provider collaboration contributes to improved patient self
      care by promoting greater agreement on patient-specific treatment goals and
      strategies. However, this hypothesis has not been tested in actual encounters of
      patients with their own physicians. OBJECTIVE: To assess the extent to which
      patients with type 2 diabetes agree with their primary care providers (PCPs) on
      diabetes treatment goals and strategies, the factors that predict agreement, and
      whether greater agreement is associated with better patient self-management of
      diabetes. DESIGN: One hundred twenty-seven pairs of patients and their PCPs in
      two health systems were surveyed about their top 3 diabetes treatment goals
      (desired outcomes) and strategies to meet those goals. Using several measures to
      evaluate agreement, we explored whether patient characteristics, such as
      education and attitudes toward treatment, and patient-provider interaction
      styles, such as shared decision making, were associated with greater agreement on
      treatment goals and strategies. We then examined whether agreement was associated
      with higher patient assessments of their diabetes care self-efficacy and self
      management. RESULTS: Overall, agreement on top treatment goals and strategies was
      low (all kappa were less than 0.40). In multivariable analyses, however, patients
      with more education, greater belief in the efficacy of their diabetes treatment,
      and who shared in treatment decision making with their providers were more likely
      to agree with their providers on treatment goals or strategies. Similarly,
      physician reports of having discussed more content areas of diabetes self-care
      were associated with greater agreement on treatment strategies. In turn, greater
      agreement on treatment goals and strategies was associated both with higher
      patient diabetes care self-efficacy and assessments of their diabetes self
      management. CONCLUSION: Although patients and their PCPs in general had poor
      agreement on goals and strategies for managing diabetes, agreement was associated
      with higher patient self-efficacy and assessments of their diabetes self
      management. This supports the hypothesis that enhancing patient-provider
      agreement on both overall treatment goals and specific strategies to meet these
      goals may lead to improved patient outcomes.

PMID- 14687275
TI  - Physician compliance with outpatient oral anticoagulant guidelines in Auvergne,
      France.
AB  - OBJECTIVE: Oral anticoagulants (OA) are commonly used, but they can lead to
      severe bleeding. We studied the indications and monitoring of OA in patients
      treated by general practitioners. DESIGN: Retrospective cross-sectional study.
      SETTING: Primary care. PATIENTS: Four hundred thirty-eight randomly selected
      patients of a population of 2,452 patients treated with OA were studied.
      INTERVENTIONS: We compared the indications for OA as reported by general
      practitioners with indications as defined according to recent guidelines. MAIN
      RESULTS: Twenty-five percent of patients should not have been treated with OA.
      Inappropriate indications (13% of patients) were atrial fibrillation without risk
      factor (3.9%), prior uncomplicated myocardial infarction (2.7%), peripheral
      arterial disease (2.7%), superficial thrombophlebitis (2.3%), and
      atherothrombotic ischemic stroke (1.6%). For 12% of patients, the duration of OA
      was too long (venous thromboembolism without permanent risk factor in 10%).
      Frequency of International Normalized Ratio (INR) measurement was insufficient
      for 14% of patients and target INR was not achieved in 31%. CONCLUSIONS: Our
      study demonstrated that clinicians' adherence to recommendations regarding
      indications for OA and management of this treatment should be improved.
      Implementation of anticoagulation clinics is probably needed.

PMID- 14687276
TI  - African American church participation and health care practices.
AB  - BACKGROUND: While religious involvement is associated with improvements in
      health, little is known about the relationship between church participation and
      health care practices. OBJECTIVES: To determine 1) the prevalence of church
      participation; 2) whether church participation influences positive health care
      practices; and 3) whether gender, age, insurance status, and levels of
      comorbidity modified these relationships. DESIGN: A cross-sectional analysis
      using survey data from 2196 residents of a low-income, African-American
      neighborhood. MEASUREMENTS: Our independent variable measured the frequency of
      church attendance. Dependent variables were: 1) Pap smear; 2) mammogram; and 3)
      dental visit-all taking place within 2 years; 4) blood pressure measurement
      within 1 year, 5) having a regular source of care, and 6) no perceived delays in
      care in the previous year. We controlled for socioeconomic factors and the number
      of comorbid conditions and also tested for interactions. RESULTS: Thirty-seven
      percent of community members went to church at least monthly. Church attendance
      was associated with increased likelihood of positive health care practices by 20%
      to 80%. In multivariate analyses, church attendance was related to dental visits
      (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.3 to 1.9) and blood
      pressure measurements (OR, 1.6; 95% CI, 1.2 to 2.1). Insurance status and number
      of comorbid conditions modified the relationship between church attendance and
      Pap smear, with increased practices noted for the uninsured (OR, 2.3; 95% CI, 1.2
      to 4.1) and for women with 2 or more comorbid conditions (OR, 1.9; 95% CI, 1.1 to
      3.5). CONCLUSION: Church attendance is an important correlate of positive health
      care practices, especially for the most vulnerable subgroups, the uninsured and
      chronically ill. Community- and faith-based organizations present additional
      opportunities to improve the health of low-income and minority populations.

PMID- 14687277
TI  - Promoting signing of advance directives in faith communities.
AB  - OBJECTIVE: To develop a participatory educational program implemented in faith
      communities that would increase discussion and signing of two types of advance
      directives-living will and durable power of attorney for health care decisions.
      DESIGN: Longitudinal study with four annual cycles of program implementation,
      evaluation, and revision incorporating a program that fostered the discussion,
      signing, and/or revision of advance directives. The program involved an
      educational workbook and ongoing support by parish nurses. SETTING: Seventeen
      faith communities in Wichita, Kansas. Faith communities included several
      predominantly white congregations, as well as several primarily African-American
      and Hispanic congregations. PARTICIPANTS: Seventeen faith communities, their
      pastors, and 25 parish nurses worked with 361 self-selected residents, living in
      community settings, to participate in the program as members of their faith
      communities. Congregations were recruited by the executive director of a local
      interfaith ministries organization and parish nurses. MAIN RESULTS: Two hundred
      forty-eight (69%) of the congregants who started the program completed it. Of the
      program completers, 83 (33%) had a directive prior to the program and 140 (56%)
      had a directive after completion. One hundred eighty-six of the completers
      discussed directives with family members. Overall, 89 (36%) of the 248 program
      completers revised an existing directive or signed one for the first time. Age
      was positively related to having signed/revised a directive prior to the program.
      Fear that advance directives would be used to deny medical care was negatively
      related to signing both prior to the program and after program completion, and
      contributed to participants' reluctance to sign directives. CONCLUSIONS:
      Educational programs implemented by parish nurses in faith communities can be
      effective in increasing rates of discussion, revision, and/or signing of advance
      directives.

PMID- 14687278
TI  - Health care for homeless women.
AB  - OBJECTIVE: Homelessness is a significant and growing problem in the United
      States. Women and families are the fastest growing segments of the homeless
      population. Homelessness increases the risk of having health problems and
      encountering barriers to care. This study determines how much perceived unmet
      need for medical care there is among homeless women, what homeless women perceive
      to be barriers to health care, and how barriers and other factors are associated
      with unmet needs. DESIGN: Cross-sectional study of homeless women, utilizing
      structured interviews. SETTING AND PARTICIPANTS: Community-based probability
      sample of 974 homeless women aged 15 to 44 years. MAIN OUTCOME MEASURES:
      Perceived unmet need for medical care in the past 60 days. Relationship between
      unmet need and demographic variables, place of stay, source of health care,
      insurance, and perceived barriers to care. RESULTS: Of the 974 women, 37%
      reported unmet need for medical care. Controlling for other factors, the odds of
      unmet need were lower among those with a regular source of care (odds ratio [OR]
      to.35, 95% confidence interval [CI],.21 to 58), while having health insurance was
      not significantly associated. The odds of unmet need were higher among those who
      experienced the barriers: not knowing where to go (OR 2.27, 95% CI, 1.40 to
      3.69), long office waiting times (OR 1.89, 95% CI 1.27 to 2.83) and being too
      sick to seek care (OR 2.03, 95% CI, 1.14 to 3.62). CONCLUSIONS: There is
      significant unmet need for medical care among homeless women. Having a regular
      source of care was more important than health insurance in lowering the odds of
      unmet need. Homeless women must be educated regarding sources of care, and
      clinics serving the homeless must decrease waiting times.

PMID- 14687279
TI  - Health care of homeless veterans.
AB  - It is important to understand the needs of those veterans who are homeless. We
      describe characteristics of homeless male veterans and factors associated with
      needing VA benefits from a two-city, community survey of 531 homeless adults.
      Overall, 425 were male, of whom 127 were veterans (29.9%). Significantly more
      veterans had a chronic medical condition and two or more mental health
      conditions. Only 35.1% identified a community clinic for care compared with 66.8%
      of non-veterans (P <.01); 47.7% identified a shelter-based clinic and 59.1%
      reported needing VA benefits. Those reporting this need were less likely to
      report a medical comorbidity (58.7% vs 76.9%; P =.04), although 66.7% had a
      mental health comorbidity and 82.7% met Diagnosic Screening Manual (DSM)-IIIR
      criteria for substance abuse/dependence. They were also significantly more likely
      to access shelter clinics compared with veterans without this need. Homeless
      veterans continue to have substantial health issues. Active outreach is needed
      for those lacking access to VA services.

PMID- 14687280
TI  - Incidence of venous thromboembolic events among nursing home residents.
AB  - Chronic care facility stay has been shown to be an independent risk factor for
      venous thromboembolism. Review of the literature, however, reveals a paucity of
      data addressing the issue of venous thromboembolism in nursing home residents.
      The purpose of this study was to determine the incidence of venous thromboembolic
      events among nursing home residents. A retrospective cohort study was derived
      from data compiled in the State of Kansas Minimum Data Set (MDS) for nursing home
      residents from July 1, 1997 to July 1, 1998. A total of 18,661 residents (median
      age, 85 years, 74% female, 95% white) satisfied the study criteria. The outcome
      measures of the primary endpoint-development of a venous thromboembolic event
      (VTE)-were obtained from the MDS quarterly health assessments and the Medicare
      ICD-9 codes. We determined the incidence of VTE among nursing home residents as
      1.30 events per 100 person-years of observation.

PMID- 14687281
TI  - Meta-analysis of vascular and neoplastic events associated with tamoxifen.
AB  - OBJECTIVE: Tamoxifen reduces the risk of developing breast cancer but also
      affects the risks of certain vascular and neoplastic events. Our purpose was to
      estimate the effects of tamoxifen on potentially life-threatening vascular and
      neoplastic outcomes. DESIGN: Random effects meta-analysis of published randomized
      controlled trials. PATIENTS: Participants in all trials in which a treatment arm
      that included tamoxifen was compared to a similar control arm. Breast cancer risk
      reduction and treatment trials were included. INTERVENTIONS: Tamoxifen at
      variable dose and duration. MEASUREMENTS AND MAIN RESULTS: Thirty-two trials
      (52,929 patients) reported one or more outcomes of interest. Tamoxifen was
      associated with significantly increased risks of endometrial cancer (relative
      risk [RR] 2.70; 95% CI, 1.94 to 3.75), gastrointestinal cancers (RR 1.31; 95% CI,
      1.01 to 1.69), strokes (RR 1.49; 95% CI, 1.16 to 1.90), and pulmonary emboli (RR
      1.88; 95% CI, 1.77 to 3.01). Tamoxifen had no effect on secondary malignancies
      other than endometrial and gastrointestinal cancers (RR 0.96; 95% CI, 0.81 to
      1.13). In contrast, tamoxifen significantly decreased myocardial infarction
      deaths (RR 0.62; 95% CI, 0.41 to 0.93) and was associated with a statistically
      insignificant decrease in myocardial infarction incidence (RR 0.90; 95% CI, 0.66
      to 1.23). Postmenopausal women had greater risk increases for neoplastic
      outcomes. CONCLUSIONS: This meta-analysis of randomized trials found tamoxifen
      use to be significantly associated with several neoplastic and vascular outcomes.
      Consideration of tamoxifen use requires balance of potential benefits and risks.

PMID- 14687283
TI  - Why does framing influence judgment?

PMID- 14687282
TI  - Describing treatment effects to patients.
AB  - OBJECTIVE: To examine the impact of different presentations of equivalent
      information (framing) on treatment decisions faced by patients. DESIGN: A
      systematic review of the published literature was conducted. English language
      publications allocating participants to different frames were retrieved using
      electronic and bibliographic searches. Two reviewers examined each article for
      inclusion, and assessed methodological quality. Study characteristics were
      tabulated and where possible, relative risks (RR; 95% confidence intervals) were
      calculated to estimate intervention effects. MEASUREMENTS AND MAIN RESULTS:
      Thirty-seven articles, yielding 40 experimental studies, were included. Studies
      examined treatment (N = 24), immunization (N = 5), or health behavior scenarios
      (N = 11). Overall, active treatments were preferred when outcomes were described
      in terms of relative rather than absolute risk reductions or number needed to
      treat. Surgery was preferred to other treatments when treatment efficacy was
      presented in a positive frame (survival) rather than a negative frame (mortality)
      (relative risk [RR] = 1.51, 95% confidence interval [CI], 1.39 to 1.64). Framing
      effects were less obvious for immunization and health behavior scenarios. Those
      with little interest in the behavior at baseline were influenced by framing,
      particularly when information was presented as gains. In studies judged to be of
      good methodological quality and/or examining actual decisions, the framing
      effect, although still evident, was less convincing compared to the results of
      all included studies. CONCLUSIONS: Framing effects varied with the type of
      scenario, responder characteristics, scenario manipulations, and study quality.
      When describing treatment effects to patients, expressing the information in more
      than one way may present a balanced view to patients and enable them to make
      informed decisions.

PMID- 14687284
TI  - Health care and faith communities: how are they related?

PMID- 14687285
TI  - Taking it to the streets: homelessness, health, and health care in the United
      States.

PMID- 14687286
TI  - Guest editorial: living in a nursing home.

PMID- 14687287
TI  - Aggression towards health care staff in a UK general hospital: variation among
      professions and departments.
AB  - BACKGROUND: Aggression towards health care staff is an increasing problem and
      although many studies have examined psychiatric settings, few have considered
      general hospitals and in particular, variation among professions and locations.
      In addition, studies often fail to include all forms of aggression such as
      threatening behaviour and verbal aggression. METHODS: This study extends existing
      research by evaluating physical assault, threatening behaviour and verbal
      aggression from patients/visitors towards general hospital staff in the context
      of different professions and departments. RESULTS AND CONCLUSIONS: The survey of
      staff showed that aggression is widespread. Within the preceding year, 27% of the
      respondents were assaulted, 23% experienced threatening behaviour from patients
      and 15.5% experienced threatening behaviour from visitors. Over 68% reported
      verbal aggression, 25.7% experiencing it more regularly than monthly. By
      departments, over 42% of the medical department staff, 36% of the surgical staff
      and over 30% of the Accident and Emergency staff were assaulted. By profession,
      staff nurses and enrolled nurses reported the most assaults (43.4%) and doctors,
      the fewest (13.8%). Other nursing grades and health care professions all reported
      levels of physical assault in excess of 20%. Correspondingly high levels of
      threatening behaviour and verbal aggression were also reported although the
      patterns of victimization differed according to the various professions and
      departments. Independently, significant levels of assault, threatening behaviour
      and verbal aggression were reported. When aggregated they demonstrate the higher
      levels of victimization that general hospital staff experienced on a regular
      basis. RELEVANCE TO CLINICAL PRACTICE: Institutional averages actually obscure
      the much higher levels of aggression experienced by the particular professions in
      particular departments. This study helps to localize the problem and identify
      those at most risk, but more research is needed into the aetiology of the
      aggression and of vulnerability factors associated with victimization.

PMID- 14687288
TI  - Spirituality: the emperor's new clothes?
AB  - BACKGROUND: This paper explores the concept of 'spirituality' with reference to
      the Patients' Charter that stipulates that a person's religious, spiritual and
      cultural needs should be respected at all times. AIMS AND OBJECTIVES: The aim is
      to offer a critical analysis of what the word 'spirituality' may mean when used
      in the Patients' Charter and to explore the implications of this for clinical
      practice. DESIGN: A critical discussion based on a literature review, examining
      in particular methodological presuppositions. METHODS: The meaning of
      'spirituality' in the Judaeo-Christian biblical traditions is explored. Some of
      the heuristic assumptions in contemporary research on 'spirituality' are
      examined. Philosophical (i.e. non-scientific) and scientific questions to do with
      'spirituality' are disentangled. RESULTS AND CONCLUSIONS: The paper concludes
      that: (i) 'Spirituality' is an elastic term not capable of universal definition
      as each person's spirituality is an individual matter for them and (ii) tools
      that are being developed for identifying a person's spirituality run the risk of
      making wrong presuppositions about what comprises spirituality. RELEVANCE TO
      CLINICAL PRACTICE: It is unlikely that tools can be developed that are widely
      applicable for identifying and assessing spirituality.

PMID- 14687289
TI  - 'Rage against the machine?': nurses' and midwives' experiences of using
      Computerized Patient Information Systems for clinical information.
AB  - BACKGROUND: Computerized Patient Information Systems (CPIS) are used increasingly
      in health care, yet few studies have asked clinicians to describe their
      experiences of using these systems and what they mean to their practice and
      patient care. AIMS AND OBJECTIVES: The aim of this study was to explore clinical
      nurses' and midwives' perceptions and understandings of computerized information
      systems in everyday practice. The objective was to provide a detailed and
      faithful account of clinicians' experiences of using such systems. DESIGN: A
      qualitative design was used, based upon interpretive phenomenology. METHODS: A
      total of 13 focus groups involving 53 practitioners was conducted in hospitals
      across five Australian states with nurses and midwives from a wide range of
      practice settings. The participants ranged from Level 1 RNs to Clinical Nurse
      Consultants and nurses with an IT project management role. RESULTS: This study
      focuses specifically on clinicians' experiences of using CPIS to manage clinical
      information. Clinicians' experiences were characterized by digital disappointment
      rather than electronic efficiencies. Clinicians reported generally that
      computerization had neither enhanced their clinical practice nor patient care,
      nor had it improved patient outcomes. CONCLUSIONS: Participants' experiences were
      predominantly negative and mostly critical of CPIS and their: perceived inability
      to capture 'real nursing', difficulty in use, incompatibilities, non
      responsiveness and irrelevance to patient care and meaningful clinical outcomes.
      RELEVANCE TO CLINICAL PRACTICE: Technological 'solutions' to health care problems
      are endlessly seductive and easily entrance policy and decision makers.
      Computerization will continue to impact upon clinical practice and cannot be
      wished away. Today's computerized systems may have been developed with scant
      regard for clinician end-users. A crucial issue facing everyone in health
      informatics is how point-of-care systems can be developed in ways that involve
      clinicians meaningfully and which recognize and respond to the complexity and
      subtlety of the world of nursing and midwifery practice.

PMID- 14687290
TI  - Effectiveness of nurse prescribing: a review of the literature.
AB  - BACKGROUND: In the UK, the number of nurses able to prescribe medicines is
      rapidly increasing in line with Government policy directives. Whilst a number of
      research studies have been conducted on nurse prescribing, review and synthesis
      of the findings from these studies had not been undertaken. AIMS AND OBJECTIVES:
      The literature review was conducted to identify key findings about the impact and
      effectiveness of nurse prescribing as well as under-researched issues, in order
      to inform future research, education and practice in this area. METHODS: A review
      of the literature on the first phase of nurse prescribing (1993-2002) in the UK
      was undertaken using electronic databases and specified search terms; some hand
      searching and identification of grey literature was also carried out. RESULTS:
      Eighteen research-based publications were included in the review. Findings
      indicate that patients are generally satisfied with district nurses' and health
      visitors' prescribing in the first phase of nurse prescribing. Nurses who
      prescribe are also generally satisfied with their role, although some concerns
      about the adequacy of their pharmacological knowledge have been raised. There is
      some variation in the prescribing patterns of district nurses', health visitors'
      and practice nurses, and the limitations of the original Nurse Prescribers'
      Formulary (NPF) have been highlighted. Some preconditions for good nurse
      prescribing practice have begun to be identified. Some nurse prescribing outcomes
      - e.g. its impact on the prescribing practices of doctors, and the perspectives
      of certain patient groups - remain un-evaluated. Research into the first phase of
      nurse prescribing is inevitably confined to those with a district nurse and/or
      health visitor qualification who were prescribing from the original NPF, thus
      limiting conclusions that can be drawn for the current policy context.
      CONCLUSIONS: The review highlights that nurse prescribing has generally been
      evaluated positively to date; however, there are both methodological weaknesses
      and under-researched issues that point to the need for further research into this
      important policy initiative. RELEVANCE TO CLINICAL PRACTICE: The review focuses
      on a clinical issue central to current and future forms of health care practice.
      Findings from the review highlight both the impact of nurse prescribing and the
      prerequisites that require consideration by those responsible for the development
      of nurse prescribing in clinical practice.

PMID- 14687291
TI  - Standardized care plans: experiences of nurses in Taiwan.
AB  - BACKGROUND: Nursing care plans have been viewed as structured plans of action for
      patient care. Studies have investigated the outcomes or effectiveness of using
      different types of care plans, but have seldom reported nurses' perceptions of
      using care plans in daily practice. AIMS AND OBJECTIVES: The purpose of this
      study was to explore nurses' experiences using a standardized care plan. DESIGN:
      Nineteen clinical nurses at a teaching hospital in Taiwan were interviewed one-on
      one and in depth from April to June 2000. Data analysis was based on Miles and
      Huberman's data reduction, data display, and a conclusion verification process to
      identify themes and concepts that represented nurses' experiences using a care
      plan. RESULTS: The following themes emerged from the interview data: being
      reminded of care procedures, time-saving in making care plans, time-consuming in
      making shift reports, undesirable content design, and paperwork-oriented/not
      patient-centered. CONCLUSION: With the considerable amounts of money spent on
      education and training to meet nurses' needs, a careful examination of nurses'
      experiences in using care plans, should assist in care plan development and lead
      to observable effects on patient care. RELEVANCE TO CLINICAL PRACTICE: Nursing
      documentation reflects nurses' observations, assessments, and interventions. It
      is expected that better use of standardized care plans will enhance nurses'
      access to appropriate and accurate information in decision-making, thus improving
      the charting process and care quality.

PMID- 14687292
TI  - Nurse-patient communication: an exploration of patients' experiences.
AB  - BACKGROUND: Patient-centred communication is a basic component of nursing and
      facilitates the development of a positive nurse-patient relationship which, along
      with other organizational factors, results in the delivery of quality nursing
      care. Nurses are frequently described in the literature as poor communicators,
      however, very few studies have examined patients' experiences of how nurses
      communicate. AIMS AND OBJECTIVES: The aim of the study was to explore and produce
      statements relating to patients' experiences of how nurses communicate. DESIGN: A
      qualitative perspective using an hermeneutic phenomenological approach was
      considered to be the most appropriate methodology for this study. METHODS: Using
      purposeful sampling, eight patients in a general teaching hospital in the
      Republic of Ireland were interviewed. Data were collected using unstructured
      interviews. Data analysis was a reflective process and the findings were
      presented through the description and interpretation of themes and sub-themes.
      RESULTS: Following data analysis four themes emerged. These were, 'lack of
      communication', 'attending', empathy' and 'friendly nurses'. CONCLUSIONS: The
      findings of this study indicate that, in contrast to the literature that suggests
      that nurses are not good at communicating with patients, nurses can communicate
      well with patients when they use a patient-centred approach. However, health care
      organizations do not appear to value or recognize the importance of nurses using
      a patient-centred approach when communicating with patients to ensure the
      delivery of quality patient care. RELEVANCE TO CLINICAL PRACTICE: The implication
      of these findings for clinical practice is that the task-centred approach to
      patient care that is associated with nursing in the past, appears to be alive and
      well. If health care management want to ensure that patients receive quality
      nursing care, they will need to consider patient-centred communication to be
      essential to encourage and support nurses to communicate in this manner.

PMID- 14687293
TI  - The meaning of caring to nurses: an investigation into the nature of caring work
      in an intensive care unit.
AB  - BACKGROUND: The purpose of the study was to generate knowledge, which informs the
      discipline of nursing as caring represents an essential human need. Despite the
      wealth of research discussing caring in nursing, little is related to the highly
      technological intensive care unit environment. AIMS OF THE STUDY: To explore the
      meaning of caring to intensive care unit nurses. To determine if the meaning of
      caring to these nurses has potential for altering nursing practice and to gain an
      insight into how caring experiences were evident to them. DESIGN AND METHOD: The
      design of the study was descriptive and qualitative. Semi-structured interviews
      were conducted to collect data on the experiences of twelve nurses who were
      selected by purposive sampling. Data analysis involved using Colaizzi's reductive
      procedure. RESULTS: Findings suggest that the nurses in the study participated in
      delivering holistic and humane care of the patient and their relatives. The
      essential structure of caring was identified as a process of competent physical
      and technical action imbued with affective skills. CONCLUSIONS: This study
      revealed caring to be synonymous with nursing. The descriptive accounts of the
      nurses' experiences of caring in this study attempt to illuminate the nature of
      intensive care unit nursing. It legitimates, from the perspectives of these
      particular participants, the importance of caring. The participants described
      caring as a process involving feelings together with professional knowledge,
      competence, skill and nursing action. This involved the holistic care of the
      patient and relatives in meeting their individual needs. RELEVANCE TO CLINICAL
      PRACTICE: This study demonstrated that the lived experience of caring reflects
      the humanistic nature of nursing. It confirms that to care is human and the
      capacity to care is affirmed and actualised in caring for the critically ill
      patient and their relatives.

PMID- 14687294
TI  - Substance abuse: prevalence in a sample of nursing students.
AB  - AIMS: The aim of this research was to evaluate the prevalence of substance abuse
      in a sample of Iranian nursing students. DESIGN AND MEASUREMENTS: Four hundred
      nursing students (85.25% were females and 14.25% were male) were assessed by a
      confidential questionnaire based on DSM-IV, which was distributed, completed by
      the students and collected in the same session. FINDINGS: Mean age of the females
      was 20.3 and of males was 22.8. Of the subjects, 27.3% (21.4% of females and 61%
      of males) reported usage of substance(s) once or more sometime during their
      lives: cigarette (25.3%), alcohol (5.8%), opium (8.5%), cocaine (1.5%), hashish
      (1.5%), marijuana (0.8%) and morphine (0.5%). Only 3.8% of the participants (1.8%
      of females and 15.3% of males) reported still using substances: cigarettes
      (3.3%), alcohol (1.7%), opium (0.8%), cocaine (0.5%) and marijuana (0.3%). About
      11.8% of the subjects (10% of females and 22% of males) reported using of
      substances occasionally (at least once a month): cigarette (10.8%), alcohol
      (3.5%), opium (4.3%), cocaine (0.5%) and hashish (0.3%). Some used or were using
      more than one substance. CONCLUSIONS: Substance use was significantly related to
      sex: higher among males than females. Tobacco and opium were found to be the most
      prevalent form of substance use among students. Pleasurable purposes, habit, need
      (to avoid withdrawal symptoms) and tension were the major reasons for substance
      use. There was no report of psychedelics use. These results are, however,
      different from those studies carried out in the west, although there is some
      overlap. Cultural attitudes toward substance use quite likely affect the types
      and patterns of use. These findings can be considered when planning preventive
      and therapeutic programmes. RELEVANCE TO CLINICAL PRACTICE: Substance use can
      reduce scientific progress and academic achievement of nursing students;
      therefore, authorities of the university must be able to assess the extent of the
      problem, understand the contributing factors, recognize signs and symptoms, and
      use educational interventions in identifying and preventing substance dependency.

PMID- 14687295
TI  - Family dynamics of postnatally depressed mothers - discrepancy between
      expectations and reality.
AB  - BACKGROUND: The birth of a new family member always brings changes to family
      dynamics. The family has to adjust to a new situation and, although the time
      after childbirth is happy for most families, postnatal depression affects 10-15%
      of mothers annually. AIMS AND OBJECTIVES: The purpose of this study was to
      ascertain families' experiences of family dynamics when the mother suffers from
      postnatal depression. DESIGN: Nine families (nine mothers, five fathers) where
      the mother had displayed symptoms of postnatal depression took part for the
      study. METHODS: Data were collected through interviews with nine families where
      the mother had scored 13 or more on the Edinburgh Postnatal Depression Scale,
      completed 6-8 weeks after childbirth. Families were offered the opportunity to
      volunteer for the interview while taking part in a follow-up study of postnatal
      depression in Finland. Interviews were analysed using the principles of grounded
      theory. RESULTS: The findings showed that there was great discrepancy between
      expectations and reality in the depressed mothers' families. Parents, especially
      mothers, strove for perfection, perceived the infant to tie them down and had
      high expectations of family life. CONCLUSIONS: Everyday family life and human
      relationships change, the depression and the parents' attitudes towards the
      infant manifest themselves in different ways, and support is of great importance.
      RELEVANCE TO CLINICAL PRACTICE: Women, especially those expecting their first
      child need a great deal of information about mood changes after childbirth and
      the opportunity to discuss the changes brought about by the birth of a child.

PMID- 14687296
TI  - Midwifery care: development of an instrument to measure quality based on the
      World Health Organization's classification of care in normal birth.
AB  - AIMS AND OBJECTIVES: The aim of the study was to develop an instrument to measure
      midwifery care in relation to World Health Organization's classification of care
      in normal birth and to test the instrument for content validity and inter-rater
      reliability. METHODS: The Delphi method was used for development of the
      instrument and to elicit evidence of content validity. Six experts from three
      different geographical regions in Sweden, representing clinically working
      midwives, lecturers in midwifery and obstetricians, participated in the first
      part of the study. The instrument was tested for inter-rater reliability in an
      exploratory study by two midwives and one of the authors. Data were analysed
      using percentage of agreement level and the Kappa coefficient. RESULTS: Five
      expert rounds were needed to reach consensus for content validity. The inter
      rater reliability test showed high agreement levels (95.9, 94.2 and 95.7%) and
      good to very good Kappa coefficients (0.74-1.0). The final instrument consisted
      of 78 items divided into five sections: background (five items); practices which
      are demonstrably useful and should be encouraged (55 items); practices which are
      clearly harmful or ineffective and should be eliminated (five items); practices
      for which insufficient evidence exists to support a clear recommendation and
      which should be used with caution while further research clarifies the issue
      (four items); and finally practices which are frequently used inappropriately
      (nine items). CONCLUSIONS AND RELEVANCE TO CLINICAL PRACTICE: The instrument can
      be used at a labour ward to measure documented care and quality of midwifery
      care. The results can be used to identify areas for improvements, to develop
      guidelines towards evidence-based care and to improve documentation. However, the
      present study should be regarded as an exploratory study and the feasibility of
      the instrument remains to be tested in empirical studies.

PMID- 14687297
TI  - Cognitive therapy integrated with life review techniques: an eclectic treatment
      approach for affective symptoms in older adults.
AB  - BACKGROUND: An important aspect of nursing theory development has been the
      adaptation of theory from other disciplines within the metaparadigm of nursing.
      This eclectic approach to theory development enhances the broad humanistic theory
      base on which effective, professional nursing practice is based. AIMS AND
      OBJECTIVES: The aim of this article is to describe the process of integrating two
      distinct psychotherapeutic approaches into one coherent mental health nursing
      intervention for the treatment of affective symptoms in older adults. Guidelines
      for using this integration process in psychiatric mental health nursing clinical
      practice are presented and illustrated through the case study approach. METHODS:
      A case study is presented describing a clinical situation in which life review
      techniques were used to enhance the outcomes of a cognitive therapy experience
      for older adults enrolled in outpatient psychotherapy treatment for acute
      adjustment disorder with an affective component. CONCLUSIONS AND RELEVANCE TO
      CLINICAL PRACTICE: The advanced practice psychiatric mental health nurse who
      approaches psychotherapeutic interventions with older adult clients from an
      eclectic approach can achieve successful outcomes by having a clear understanding
      of (i) the dynamics of the various psychotherapeutic approaches, (i) the skill
      level of the practitioner, (iii) the psychosocial sophistication of the client,
      and (iv) the pathology being treated. In addition, active involvement by the
      client in a treatment process that matches his/her psychosocial skill and coping
      resource level will contribute to effective resolution of pathology. A cognitive
      therapy approach supplemented by life review techniques is an excellent example
      of an effective, eclectic treatment approach of affective disorders in older
      adults.

PMID- 14687298
TI  - Older patients with chronic heart failure within Swedish community health care: a
      record review of nursing assessments and interventions.
AB  - BACKGROUND: Older patients with chronic heart failure constitute a large group
      within community home care that is at high risk for re-hospitalization. However,
      hospital readmission can be prevented if early signs of deterioration are
      recognized and proper interventions applied. AIMS AND OBJECTIVES: The aim of the
      study was to audit nursing care for older chronic heart failure patients within
      the Swedish community health care system. DESIGN: The study adopted a
      retrospective descriptive design. METHODS: In a Swedish urban municipality
      nursing documentation from 161 records on patients diagnosed with chronic heart
      failure was collected retrospectively from community nursing home care units.
      Patient records were reviewed for characteristics of nursing care and assessed
      for comprehensiveness in recording. RESULTS: The main results showed that medical
      care of patients with chronic heart failure was poorly recorded, making it
      possible only to follow fragments of the care process. The nursing notes showed
      poor adherence to current clinical guidelines. Only 12% of the records contained
      notes on patients' body weight and only 4% noted patients' knowledge about
      chronic heart failure. When interventions did occur, they largely consisted of
      drug administration. CONCLUSIONS: The findings revealed flaws in the recording of
      specific assessment and interventions as well as poor adherence to current
      international clinical guidelines. RELEVANCE TO CLINICAL PRACTICE: Supportive
      guidelines available at the point of care are needed to enhance proper community
      based home health care for older patients with chronic heart failure.

PMID- 14687299
TI  - Time distribution of selected care activities in home care in Germany.
AB  - AIMS AND OBJECTIVES: To investigate the time required by family caregivers to
      carry out selected care activities. The project was initiated by the responsible
      ministry for German Long Term Care Insurance. The Long Term Care Insurance
      provides recommendations for specific time ranges for care activities as a basis
      for assessment. METHODS: Cross-sectional descriptive study, convenience sample of
      200 households. Time was measured during direct observation using a stopwatch
      (time-and-motion method). RESULTS: The time taken for care activities had large
      standard deviations. For many activities, <50% of the cases fell in the
      recommended time range. No significant influences on the different durations were
      found. CONCLUSIONS: The results give no support for the assumption that
      recommended time ranges can enhance assessment comparability and adequacy.
      RELEVANCE TO CLINICAL PRACTICE: In order to predict the amount of work in nursing
      it is more important to assess the patient's situation and history, and the goal
      to be reached by nursing care than to know the title of the required nursing
      intervention.

PMID- 14687300
TI  - Doctors' and nurses' perceptions of interdisciplinary collaboration in the NICU,
      and the impact of a neonatal nurse practitioner model of practice.
AB  - BACKGROUND: The importance of interdisciplinary collaboration has been attested
      to by a number of authors. Some have suggested that Nurse Practitioners (NPs) may
      be able to improve collaboration between doctors and nurses, but this assertion
      does not appear to have been researched. AIMS AND OBJECTIVES: To investigate
      doctors' and nurses' perceptions of interdisciplinary collaboration in two
      neonatal intensive care units, and to assess the impact of a Neonatal Nurse
      Practitioner (NNP) practice model on these perceptions. The study was conducted
      as part of a larger project to develop a NNP model of practice. DESIGN: Survey,
      pre- and post-intervention. METHODS: Medical and nursing staff in both units were
      surveyed before and after introduction of the NP model of practice. The
      instrument consisted of 25 statements relating to nurse-doctor interactions, with
      which respondents indicated their level of agreement on a five-point Likert
      scale. The Mann-Whitney U-test was used to compare scores for individual items
      and for overall collaboration between various groups of staff, and between the
      first and second surveys. RESULTS: Significant differences between the responses
      of nurses and doctors were found on both surveys. Areas of disagreement chiefly
      concerned doctors' behaviour and their attitudes towards nurses, rather than
      nurses' behaviour or environmental factors. Doctors consistently reported a
      higher degree of collaboration than did nurses. Few differences were found
      between first and second surveys. CONCLUSIONS: Results suggest that problems in
      nurse-physician interactions exist in both units. No impact of the NNP role, as
      established in this project, on interdisciplinary collaboration could be
      demonstrated. Further research in this area is warranted.

PMID- 14687301
TI  - Objective assessment of self-care and non-professional care: a proposal.

PMID- 14687302
TI  - Spiritual coping mechanisms in chronic illness: a qualitative study.

PMID- 14687303
TI  - Comparison of the experiences of having a sick baby in a neonatal intensive care
      unit among mothers with and without the right of abode in Hong Kong.

PMID- 14687304
TI  - Postnatal depression: a qualitative study of the experiences of a group of Hong
      Kong Chinese women.

PMID- 14687305
TI  - Depression in nursing students.

PMID- 14687307
TI  - State of the journal: 3 years and looking ahead.

PMID- 14687306
TI  - Commentary on Oh H. and Seo W. (2003) Sensory stimulation programme to improve
      recovery in comatose patients. Journal of Clinical Nursing 12, 394-404.

PMID- 14687308
TI  - Nutritional formula enhanced immune function and reduced days of symptoms of
      upper respiratory tract infection in seniors.
AB  - OBJECTIVES: To assess whether an experimental nutritional formula, given as a
      supplement, would reduce days of symptoms of upper respiratory tract infection
      (URTI) and affect antibody and lymphocyte proliferative responses to influenza
      vaccine. DESIGN: A prospective, randomized, double-blind, controlled trial was
      conducted between October 1999 and April 2000. SETTING: Assisted- and independent
      living facilities in North Central Florida. PARTICIPANTS: Sixty-six individuals,
      aged 65 and older. INTERVENTION: Subjects received 8 oz/d of an experimental
      formula containing antioxidants, zinc, selenium, fermentable oligosaccharides,
      and structured triacylglycerol or an isoenergetic, isonitrogenous control formula
      for 183 days. MEASUREMENTS: Subjects recorded daily symptoms of URTI. Antibody
      titers and lymphocyte proliferation to three influenza vaccine components were
      measured on Days 57 and 183. RESULTS: Eighteen subjects in the control group and
      16 subjects in the experimental group consumed an average of 7 ounces of formula
      daily and completed the 183-day study. Median days of symptoms of URTI were 3
      (range 0-69, total days=156) and 0 (range 0-49, total days=78) for the control
      and experimental groups, respectively (P=.049). On Day 57, seven of 17 (41%)
      subjects in the control group and 13 of 15 (87%) subjects in the experimental
      group achieved a fourfold or greater increase in serum antibody titer to
      A/Beijing (P=.012). Lymphocyte proliferation to influenza vaccine components was
      greater in the experimental (median=1,365 cpm, range=0-14,955 cpm) than the
      control group (median=136 cpm, range=0-4,270 cpm) (P=.013). CONCLUSION: Subjects
      consuming an experimental nutritional formula experienced enhanced immune
      function and fewer days of URTI symptoms.

PMID- 14687309
TI  - A placebo-controlled trial of a proprietary extract of North American ginseng
      (CVT-E002) to prevent acute respiratory illness in institutionalized older
      adults.
AB  - OBJECTIVES: To compare a proprietary extract of American ginseng, CVT-E002, with
      placebo in preventing acute respiratory illness (ARI) in an institutional setting
      during the influenza season. DESIGN: Two randomized, double-blind, placebo
      controlled trials conducted late in the 2000 (8 week) and 2000-2001 (12 week)
      influenza seasons. SETTING: Long-term care setting that included nursing home and
      assisted living at three sites. PARTICIPANTS: Eighty-nine (2000) and 109 (2000
      2001) enrolled subjects, average age 81 and 83.5, respectively; 74% women.
      Approximately 90% had received influenza vaccine in each of the 2 years.
      INTERVENTION: Oral twice-daily administration of a proprietary ginseng extract,
      CVT-E002, 200 mg or placebo. MEASUREMENTS: ARI was defined as two new respiratory
      symptoms or one with a constitutional symptom. Confirmation of viral ARI was by
      culture (influenza or respiratory syncytial virus (RSV)) or serology for
      influenza. Laboratory safety monitoring was done at 0, 4, and 8 or 12 weeks.
      RESULTS: An intent-to-treat analysis of pooled data corrected for drug exposure
      time showed that the incidence of laboratory-confirmed influenza illness (LCII)
      was greater in placebo- (7 cases/101 subjects) than CVT-E002-treated (1/97)
      groups (odds ratio (OR)=7.73, P=.033). Combined data for LCII and RSV illness
      were also greater in placebo- (9/101) than CVT-E002-treated (1/97) groups
      (OR=10.50, P=.009), for an overall 89% relative risk reduction of ARI in the CVT
      E002 group. CONCLUSION: CVT-E002 was shown to be safe, well tolerated, and
      potentially effective for preventing ARI due to influenza and RSV.

PMID- 14687310
TI  - Can a short period of micronutrient supplementation in older institutionalized
      people improve response to influenza vaccine? A randomized, controlled trial.
AB  - OBJECTIVES: To test the hypothesis that a micronutrient supplement can improve
      seroconversion after influenza immunization in older institutionalized people.
      DESIGN: : Randomized, double-blind, placebo-controlled study. SETTING: Nursing
      and residential homes in Liverpool, United Kingdom. PARTICIPANTS: One hundred
      sixty-four residents aged 60 and older from 31 homes were initially randomized;
      of these, 119 (72.6%) completed the study. INTERVENTION: Participants were
      randomized to receive a micronutrient supplement providing the reference nutrient
      intake for all vitamins and trace elements or identical placebo. Tablets were
      taken over an 8-week period during September and October 2000; influenza vaccine
      was administered 4 weeks after their commencement. MEASUREMENTS: The
      hemagglutination-inhibiting antibody response as defined by a fourfold or greater
      titer rise over 4 weeks and assessed separately for each of the three antigens
      contained in the 2000/2001 influenza vaccine (A/New Caledonia/20/99 (H1N1),
      A/Moscow/10/99 (H3N2), B/Beijing/184/93 (B)). RESULTS: Despite a significant
      increase in serum concentrations of vitamins A, C, D3, E, folate, and selenium in
      the supplemented group, there was no significant difference between groups
      (supplemented vs placebo, respectively) in the proportion of participants
      seroconverting to H1N1 (41% vs 49%, P=.374), H3N2 (49% vs 58%, P=.343), or B (41%
      vs 40%, P=.944). CONCLUSION: A micronutrient supplement providing the reference
      nutrient intake administered over 8 weeks had no beneficial effect on antibody
      response to influenza vaccine in older people living in long-term care.

PMID- 14687311
TI  - Barriers to pneumococcal and influenza vaccination in older community-dwelling
      adults (2000-2001).
AB  - OBJECTIVES: To identify facilitators of and barriers to vaccination in patients
      from a range of socioeconomic levels. DESIGN: A survey was conducted in 2001
      using computer-assisted telephone interviewing. SETTING: Patients from inner-city
      health centers and suburban practices were interviewed. PARTICIPANTS: Inclusion
      criteria were aged 66 and older and an office visit after September 30, 1998.
      MEASUREMENTS: Self-reported influenza and pneumococcal vaccination status and
      facilitating conditions, attitudes, social influences, and perceived consequences
      from the Triandis model were assessed. RESULTS: Overall, 557 interviews were
      completed with 775 eligible patients (72%). Patients who reported having received
      pneumococcal vaccine more frequently believed that their physicians recommended
      the vaccine than did the unvaccinated (97% vs 49%; P=.001). This was also true
      for influenza vaccine (99% vs 80%; P<.001). More unvaccinated patients than
      vaccinated patients felt that obtaining either vaccine was more trouble than it
      is worth (pneumococcal 19% vs 1%; P=.04, influenza 20% vs 1%; P=.004). The
      vaccinated were more likely to be willing to obtain the influenza and
      pneumococcal vaccines at the same time (pneumococcal 91% vs 59%; P=.002,
      influenza 91% vs 55%; P=.014). CONCLUSION: Physicians should take every
      opportunity to recommend vaccination to their eligible adult patients. Offering
      influenza and pneumococcal vaccines at the same visit is an acceptable means to
      ensure that adults are fully vaccinated.

PMID- 14687312
TI  - Outcomes and costs among seniors requiring hospitalization for community-acquired
      pneumonia in Alberta.
AB  - OBJECTIVES: To determine the age-specific rates of hospital discharge, cost per
      day, and overall in-hospital 1- and 4-year mortality for seniors who required
      hospitalization for the treatment of community-acquired pneumonia (CAP). DESIGN:
      Retrospective analysis of two administrative health service databases. SETTING:
      Province of Alberta, Canada. PARTICIPANTS: Residents of Alberta aged 18 and
      older. MEASUREMENTS: Hospital abstracts and vital statistics from April 1, 1994,
      to March 31, 1999, were analyzed, and mortality and cost outcomes statistically
      modeled by regression. RESULTS: There were 8,500 annual hospital discharges for
      CAP costing more than $40 million per year. The overall in-hospital all-cause
      mortality rate was 12%, and the 1-year mortality rate was 26%. The mean age of
      pneumonia cases increased (P<.000) from 62.8 in 1994/1995 to 67.2 in 1998/1999.
      The proportion of hospital discharges in those aged 85 and older was 13% in
      1994/1995, increasing to 18% in 1998/1999 (P<.000). The age-specific hospital
      discharge rate and length of hospitalization increased with age. After adjustment
      for other factors using modeling, it was found that the relative risk (RR) of in
      hospital and 1-year mortality increased with age, the RR of using special medical
      care and higher-than-average daily hospital cost decreased with age, and the RR
      of greater-than-average daily hospital cost was not associated with an increase
      in comorbidity. Total costs per hospital stay were similar in patients aged 85
      and older to those in patients aged 65 to 74, despite a one-third longer length
      of stay, which was consistent with reduced use of special medical care in those
      aged 85 and older. CONCLUSION: The increased use of hospital resources for CAP in
      the setting of an aging population may have been partially avoided because of
      limitations in care provided for seniors aged 85 and older.

PMID- 14687313
TI  - Antibiotic treatment of acute respiratory tract infections in the elderly: effect
      of a multidimensional educational intervention.
AB  - OBJECTIVES: : To measure and improve antibiotic use for acute respiratory tract
      infections (ARIs) in the elderly. DESIGN: : Prospective, nonrandomized controlled
      trial. SETTING: : Ambulatory office practices in Denver metropolitan area (n=4
      intervention practices; n=51 control practices). PARTICIPANTS: : Consecutive
      patients enrolled in a Medicare managed care program who were diagnosed with ARIs
      during baseline (winter 2000/2001) and intervention (winter 2001/2002) periods. A
      total of 4,270 patient visits were analyzed (including 341 patient visits in
      intervention practices). INTERVENTION: : Appropriate antibiotic use and
      antibiotic resistance educational materials were mailed to intervention practice
      households. Waiting and examination room posters were provided to intervention
      office practices. MEASUREMENTS: : Antibiotic prescription rates, based on
      administrative office visit and pharmacy data, for total and condition-specific
      ARIs. RESULTS: : There was wide variation in antibiotic prescription rates for
      ARIs across unique practices, ranging from 21% to 88% (median=54%). Antibiotic
      prescription rates varied little by patient age, sex, and underlying chronic lung
      disease. Prescription rates varied by diagnosis: sinusitis (69%), bronchitis
      (59%), pharyngitis (50%), and nonspecific upper respiratory tract infection
      (26%). The educational intervention was not associated with greater reduction in
      antibiotic prescription rates for total or condition-specific ARIs beyond a
      modest secular trend (P=.79). CONCLUSION: : Wide variation in antibiotic
      prescription rates suggests that quality improvement efforts are needed to
      optimize antibiotic use in the elderly. In the setting of an ongoing physician
      intervention, a patient education intervention had little effect. Factors other
      than patient expectations and demands may play a stronger role in antibiotic
      treatment decisions in elderly populations.

PMID- 14687314
TI  - Healthy elderly people lack neutrophil-mediated functional activity to type V
      group B Streptococcus.
AB  - OBJECTIVES: To determine the function of capsular polysaccharide (CPS)-specific
      immunoglobulin-G (IgG) and neutrophils from older adults in increasing ingestion
      and killing of type V group B Streptococcus (GBS). DESIGN: Cross-sectional study.
      SETTING: Outpatient clinic at Baylor College of Medicine. PARTICIPANTS: The
      subjects were 40 healthy, community-dwelling adults aged 65 and older from
      Houston, Texas. MEASUREMENTS: The serum level of type V GBS CPS-specific IgG was
      measured using an enzyme-linked immunosorbent assay. Functional activity was
      evaluated using an opsonophagocytosis assay. RESULTS: Sera from four subjects
      promoted efficient neutrophil-mediated phagocytosis and killing of type V GBS
      (mean log10 reduction+/-standard deviation in colony-forming units (cfu)=1.51+/
      0.39). Each had serum CPS-specific IgG concentrations exceeding 1 microg/mL. Sera
      from 36 subjects did not promote neutrophil-mediated functional activity (mean
      log10 reduction in cfu=-0.09+/-0.06; P=.025). Only one of these 36 had a CPS
      specific IgG concentration exceeding 1 microg/mL. When pooled sera from young
      adults given type V GBS conjugate vaccine was added at CPS-specific IgG
      concentrations of 4 microg/mL or 0.4 microg/mL, sera from all subjects promoted
      neutrophil-mediated killing of type V GBS. No impairment was evident in the
      neutrophil function of elderly subjects when it was compared with that of young
      adults. CONCLUSION: CPS-specific IgG and neutrophils from healthy older adults
      function to ingest and kill type V GBS, but these antibodies are not present in
      sufficient amounts in most individuals. Further studies should determine whether
      a type V GBS vaccine induces functionally active antibodies in older people.

PMID- 14687315
TI  - Effect of do-not-resuscitate orders on hospitalization of nursing home residents
      evaluated for lower respiratory infections.
AB  - OBJECTIVES: To determine resident and facility characteristics associated with do
      not-resuscitate (DNR) orders and to test the effect of DNR orders on
      hospitalization of acutely ill nursing home (NH) residents with lower respiratory
      tract infections (LRIs). DESIGN: Prospective cohort. SETTING: Thirty-six NHs
      (almost 4,000 residents) in central and eastern Missouri in the Missouri Lower
      Respiratory Infection study. PARTICIPANTS: NH residents with a LRI (n=1031).
      MEASUREMENTS: Data were obtained from new Minimum Data Set evaluations, resident
      examination, and chart review. Associations between resident, physician, and
      facility characteristics and the presence of a DNR order and hospitalization
      within 30 days from evaluation for an LRI were analyzed. RESULTS: Sixty percent
      of subjects had a DNR order, and 2% had a do-not-hospitalize order. Resident
      characteristics associated with a DNR order included older age, white race,
      having a surrogate decision-maker, NH residence for longer than 3 years, and more
      impaired cognition. Residents with DNR orders were more likely to live in
      facilities with more licensed beds, a lower proportion of Medicaid recipients,
      and a higher prevalence of influenza vaccination. After controlling for potential
      confounders, residents with a DNR order before the acute illness episode were
      significantly less likely to be hospitalized (adjusted odds ratio=0.69, 95%
      confidence interval=0.49-0.97). CONCLUSION: DNR orders independently reduce the
      risk of hospitalization for LRI and may function as a marker for undocumented
      care limitations or as a mandate to limit care (unrelated to resuscitation) in NH
      residents with LRI.

PMID- 14687316
TI  - Nutrition risk factors for survival in the elderly living in Canadian long-term
      care facilities.
AB  - OBJECTIVES: To determine the role of nutritional parameters in influencing the
      risk of mortality in institutionalized elderly. DESIGN: A prospective cohort
      study in which subjects had several nutritional parameters measured at baseline
      and were followed for 19 months. Time to death and mortality were recorded
      starting immediately after enrollment. SETTING: Fourteen long-term care
      facilities (LTCFs). PARTICIPANTS: Four hundred eight elderly long-term care
      residents aged 60 and older who resided in the facility for more than 6 weeks.
      MEASUREMENTS: At baseline, knee height, weight, mid-arm circumference (MAC), skin
      fold thickness, and fat-free mass using bioelectric impedance analysis were
      measured. Covariates included demographic factors, length of stay in the
      facility, functional status, and medical diagnoses. Cox proportional hazards
      regression analysis was used to identify independent predictors of mortality.
      Results are reported as mean+/-standard error of the mean (SEM). RESULTS:
      Overall, mortality rate was 28.4%. Univariate predictors included male sex, body
      mass index, MAC, and triceps skin fold. In multivariate analysis, male sex
      (hazard ratio (HR)=1.7, 95% confidence interval (CI)=1.2-2.7, P=.0096) and MAC
      less than 26 cm were significantly associated with increased risk of mortality
      (HR=4.8, 95% CI: 2.8-8.3, P<.0001). CONCLUSION: Among this elderly population
      living in LTCFs, MAC is the best nutritional predictor of mortality.

PMID- 14687317
TI  - Metabolic markers of cobalamin deficiency and cognitive function in normal older
      adults.
AB  - OBJECTIVES: To investigate the relationship between metabolic markers of
      cobalamin deficiency and cognitive function in normal older adults. DESIGN: Cross
      sectional study. SETTING: Queen's University and St. Mary's of the Lake Hospital,
      Kingston, Ontario, Canada. PARTICIPANTS: Two hundred eighty-one cognitively
      normal, community-dwelling participants aged 65 and older. MEASUREMENTS: Serum
      cobalamin, red blood cell folate, methylcitric acid, homocysteine, and
      methylmalonic acid were determined. Cognitive instruments included the California
      Verbal Learning Test, Mattis Dementia Rating Scale, and the Stroop
      Neuropsychological Screening Inventory (Stroop). RESULTS: Serum levels of
      methylcitric acid had a significant negative correlation with recall, learning,
      and discriminability (factor 1) of the California Verbal Learning Test after
      adjusting for age and sex (beta=-0.138, P=.019). Subjects with elevated
      methylcitric acid had significantly lower scores (factor 1) than subjects with
      normal methylcitric acid (P<.01). Bivariate analysis showed significant
      correlations between levels of homocysteine and the Stroop score and between
      cobalamin, methylmalonic acid, and homocysteine and some scores of the California
      Verbal Learning Test, but these relationships did not remain significant after
      multivariate analysis. Subjects with high homocysteine (tHcy) had lower Stroop
      scores than subjects with normal tHcy (P<.05). No biochemical parameters were
      associated with the Mattis Dementia Rating Scale scores. CONCLUSION: This study
      indicates that, in normal elderly subjects, some cognitive scores are related to
      serum methylcitric acid and possibly homocysteine.

PMID- 14687318
TI  - The effect of equipment usage and residual task difficulty on use of personal
      assistance, days in bed, and nursing home placement.
AB  - OBJECTIVES: To determine whether residual difficulty in functioning in spite of
      equipment use is linked with increased use of personal assistance. DESIGN:
      Longitudinal. Two waves of the Asset and Health Dynamics Among the Oldest Old
      (AHEAD) database were used to test the effect of residual difficulty on hours of
      personal assistance and bed days at Wave 1 on hours of personal assistance, bed
      days, and nursing home placement at Waves 1 and 2. SETTING: A nationally
      representative setting of community-dwelling persons aged 70 and older and their
      spouses, regardless of age at Wave 1 AHEAD. There was movement of some
      respondents into nursing homes by the Wave 2 interview. PARTICIPANTS: Respondents
      to the AHEAD survey, N=8,222 at Wave 1. MEASUREMENTS: The dependent variables
      were hours of personal assistance in the month before the AHEAD survey (Waves 1
      and 2), number of days in month before the survey in which the person did not get
      out of bed (Waves 1 and 2), and residence in a nursing home at Wave 2. The key
      explanatory variable was a mutually exclusive (four category) variable that
      specified whether there was residual difficulty (yes/no) in indoor mobility in
      spite of using equipment to aid specifically with indoor mobility. The four
      category variable was defined by the four categories created by a cross
      tabulation of equipment use (yes/no) and difficulty with indoor mobility
      (yes/no). A similar four-category variable was also defined for transferring in
      the home. RESULTS: In cross section, equipment users with residual difficulty
      reported more hours of personal assistance in the case of indoor mobility
      impairment and were more likely to have some hours of personal assistance than
      those without residual difficulty with indoor mobility and transferring.
      Longitudinally, those with residual difficulty at Wave 1 were more likely to need
      some personal assistance hours at Wave 2 (odds ratio=1.67, 95% confidence
      interval= 1.23-2.26 for indoor mobility). For transferring, those with residual
      difficulty had 43 more hours of personal assistance per month (P=.001) than those
      for whom equipment resolved their disability. Residual disability was linked to
      more bed days for users of indoor mobility and transferring equipment, but it was
      not predictive of nursing home placement by Wave 2. CONCLUSION: Equipment for
      indoor mobility or transfers apparently resolves difficulty for some users of the
      equipment but not for others. Residual task difficulty in spite of equipment for
      indoor mobility and transferring is linked with worse outcomes, including
      increased dependency on personal assistance and more days in bed. This shows that
      more attention is needed to determine whether equipment prescribed is appropriate
      for a patient's difficulty and that follow-up assessment is crucial after
      equipment is prescribed.

PMID- 14687319
TI  - The healthcare costs of sarcopenia in the United States.
AB  - OBJECTIVES: To estimate the healthcare costs of sarcopenia in the United States
      and to examine the effect that a reduced sarcopenia prevalence would have on
      healthcare expenditures. DESIGN: Cross-sectional surveys. SETTING: Nationally
      representative surveys using data from the U.S. Census, Third National Health and
      Nutrition Examination Survey, and National Medical Care and Utilization
      Expenditure Survey. PARTICIPANTS: Representative samples of U.S. adults aged 60
      and older. MEASUREMENTS: The healthcare costs of sarcopenia were estimated based
      on the effect of sarcopenia on increasing physical disability risk in older
      persons. In the first step, the healthcare cost of disability in older Americans
      was estimated from national surveys. In the second step, the proportion of the
      disability cost due to sarcopenia (population-attributable risk) was calculated
      to determine the healthcare costs of sarcopenia. These calculations relied upon
      previously published relative risk values for disability in sarcopenic
      individuals and sarcopenia prevalence rates in the older population. RESULTS: The
      estimated direct healthcare cost attributable to sarcopenia in the United States
      in 2000 was $18.5 billion ($10.8 billion in men, $7.7 billion in women), which
      represented about 1.5% of total healthcare expenditures for that year. A
      sensitivity analysis indicated that the costs could be as low as $11.8 billion
      and as high as $26.2 billion. The excess healthcare expenditures were $860 for
      every sarcopenic man and $933 for every sarcopenic woman. A 10% reduction in
      sarcopenia prevalence would result in savings of $1.1 billion (dollars adjusted
      to 2000 rate) per year in U.S. healthcare costs. CONCLUSION: Sarcopenia imposes a
      significant but modifiable economic burden on government-reimbursed healthcare
      services in the United States. Because the number of older Americans is
      increasing, the economic costs of sarcopenia will escalate unless effective
      public health campaigns aimed at reducing the occurrence of sarcopenia are
      implemented.

PMID- 14687320
TI  - Efficacy, safety, and tolerability of sertraline in patients with late-life
      depression and comorbid medical illness.
AB  - OBJECTIVES: To report on the efficacy, safety, and tolerability of sertraline in
      the treatment of elderly depres-sed patients with and without comorbid medical
      illness. SETTING: Multicenter. DESIGN: Randomized, double-blind, placebo
      controlled study. PARTICIPANTS: A total of 752 patients aged 60 and older with
      diagnosis of major depressive disorder according to Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition, diagnosis. MEASUREMENTS: Outcome
      measures included the 17-item Hamilton Depression Scale (HAMD); the Clinical
      Global Depression-Severity/Improvement (CGI-S/CGI-I); efficacy and safety/adverse
      event assessments; Quality of Life, Enjoyment, and Satisfaction Questionnaire;
      and the Medical Outcomes Study 36-Item Short-Form Health Status Survey. RESULTS:
      In the overall sample, sertraline was superior to placebo on all three primary
      outcome measures, HAMD, and overall clinical severity and change (CGI-S/CGI-I).
      Furthermore, therapeutic response to sertraline was comparable in those with or
      without medical comorbidity, and there were no treatment-by-comorbidity group
      interactions. Sertraline was also associated with a faster time to response than
      placebo in the comorbid group (P<.006). Sertraline-treated patients in the
      comorbid group had similar adverse events and discontinuations when compared to
      those in the noncomorbid group. CONCLUSION: Sertraline was efficacious in
      reducing depressive symptomatology, regardless of the presence of comorbid
      medical illness. Sertraline was safe and well tolerated by patients with or
      without medical illness.

PMID- 14687321
TI  - The short-term effect of interdisciplinary medication review on function and cost
      in ambulatory elderly people.
AB  - OBJECTIVES: To determine whether a medication review by a specialized team would
      promote regimen changes in elders taking multiple medications and to measure the
      effect of regimen changes on monthly cost and functioning. DESIGN: A randomized
      controlled trial. SETTING: Health center ambulatory clinic. PARTICIPANTS:
      Community-dwelling older adults taking five or more medications were assessed at
      baseline and 6 weeks. A medication-change intervention group of 57 elders was
      compared with a control group of 76 elder adults. INTERVENTION: The primary
      intervention was a comprehensive review and recommended modification of a
      patient's medication regimen. Changes were endorsed by each patient's primary
      physician and discussed with each patient. MEASUREMENTS: Measures were the Timed
      Manual Performance Test, Physical Performance Test, Functional Reach Assessment,
      subtests from the Wechsler Adult Intelligence Scale, a modified Randt Memory
      Test, the Center for Epidemiological Studies-Depression Scale, the Self-Rating
      Anxiety Scale, and the Rand 36-item Health Survey 1.0. Comorbidity was determined
      using the International Classification of Diseases, Ninth Revision, Clinical
      Modification. Medication usage was determined using brown bag review. RESULTS:
      Intervention subjects decreased their medications by an average of 1.5 drugs. No
      differences in functioning were observed between groups. Intervention subjects
      saved an average $26.92 per month in wholesale medication costs; control subjects
      saved $6.75 per month (P<.006). CONCLUSION: Although the intervention
      significantly reduced the medications taken and monthly cost, most patients were
      resistant to reducing medications to the recommended level. Further study is
      needed to understand patient resistance to reducing adverse polypharmacy and to
      devise better strategies for addressing this important problem in geriatric
      health. Greater focus on prescriber behavior is recommended.

PMID- 14687322
TI  - Achieving goals in geriatric assessment: role of caregiver agreement and
      adherence to recommendations.
AB  - OBJECTIVES: To determine predictors of recommendation adherence and goal
      attainment of family caregivers of patients at a geriatric assessment center.
      DESIGN: One-year prospective cohort study. SETTING: Outpatient geriatric
      assessment center in Connecticut. PARTICIPANTS: Two hundred consecutive new
      patients and their family caregivers. MEASUREMENTS: : Family caregivers were
      interviewed after geriatric assessment to ascertain their treatment goals for the
      patient. Medical records were reviewed to identify treatment recommendations.
      Family caregivers were interviewed 1 year later to assess adherence to
      recommendations and attainment of goals. RESULTS: Follow-up interviews were
      completed with 176 (88%) family caregivers. Common recommendations pertained to
      physician referral (71%), medications (46%), counseling/education (31%),
      diagnostic tests (30%), residential planning (26%), healthcare planning (21%),
      and community services (21%). Goal attainment was reported in 44% to 67% of the
      patient cases, depending on goal category. Caregiver agreement with
      recommendations predicted adherence to recommendations (adjusted relative risk
      (ARR)=1.99, 95% confidence interval (CI)=1.04-5.92) after adjusting for available
      clinical and demographic factors. In addition, adherence to recommendations
      predicted goal attainment in adjusted analyses (ARR=1.70, 95% CI=1.09-2.64).
      CONCLUSION: This study revealed a broad range of treatment recommendations in
      geriatric assessment and suggests that agreeing with recommendations can promote
      adherence and that adherence can promote goal attainment. Taken together, the
      results imply that articulating shared treatment recommendations may improve the
      quality of health care.

PMID- 14687323
TI  - Effect of depression on diagnosis, treatment, and survival of older women with
      breast cancer.
AB  - OBJECTIVES: To assess the effect of a prior diagnosis of depression on the
      diagnosis, treatment, and survival of older women with breast cancer. DESIGN:
      Retrospective analysis of records from Surveillance, Epidemiology and End Results
      (SEER) and Medicare claims. SETTING: Registries from seven major cities and five
      states. PARTICIPANTS: A total of 24,696 women aged 67 to 90 diagnosed with breast
      cancer between 1993 and 1996 and included in the SEER Medicare linked database
      were studied. MEASUREMENTS: Information on patient demographics, tumor
      characteristics, treatment received, and survival were obtained from SEER, and
      the Medicare inpatient and professional charges for the 2 years before diagnosis
      were searched for a diagnosis of depression. RESULTS: A total of 1,841 of the
      24,696 women (7.5%) had been given a diagnosis of depression sometime in the 2
      years before the diagnosis of breast cancer. There was no difference in tumor
      size or stage at diagnosis between depressed and nondepressed women. Women
      diagnosed with depression were less likely to receive treatment generally
      considered definitive (59.7% vs 66.2%, P<.0001), and this difference remained
      after controlling for age, ethnicity, comorbidity, and SEER site. Also, women
      with a prior diagnosis of depression had a higher risk of death (hazard
      ratio=1.42; 95% confidence interval= 1.13-1.79) after controlling for other
      factors that might affect survival. The higher risk of death associated with a
      prior diagnosis of depression was also seen in analyses restricted to women who
      received definitive treatment. CONCLUSION: Women with a recent diagnosis of
      depression are at greater risk for receiving nondefinitive treatment and
      experience worse survival after a diagnosis of breast cancer, but differences in
      treatment do not explain the worse survival.

PMID- 14687324
TI  - Effect of a comprehensive, multidisciplinary, educational program on the use of
      antibiotics in a geriatric university hospital.
AB  - OBJECTIVES: To assess the effect of a comprehensive, educational antibiotic
      management program designed to improve antibiotic use and reduce treatment costs
      in elderly patients with suspected urinary or respiratory tract infection.
      DESIGN: Interventional cohort study with 12 cross-sectional drug utilization
      reviews of antibiotic use before, during, and after the multifaceted
      intervention. SETTING: A 304-bed university hospital for geriatric patients.
      PARTICIPANTS: A total of 3,383 elderly patients. INTERVENTIONS: An educational
      program including distribution of guidelines on the diagnosis and treatment of
      urinary and respiratory tract infections; lectures on geriatric infectious
      diseases; weekly ward rounds for patients with suspected infection; and targeted,
      individual counseling on diagnosis and antibiotic treatment of infections.
      MEASUREMENTS: Antibiotic utilization data were collected from the patients'
      records. Antimicrobial costs were calculated using 1998 hospital wholesale
      prices. RESULTS: Of 3,383 screened patients, 680 (20%) received at least one
      antibiotic. During the study period, the mean number of prescribed drugs per
      patient increased from 5.9 to 7.6 (29%; P<.001). In contrast, a reduction of 15%
      was observed in the proportion of patients exposed to antibiotic agents (P=.08)
      and a drop of 26% in the number of antibiotics administered (P<.001). This
      resulted in a 54% decrease in cumulative daily antibiotic costs. In 83 (75%) of
      110 surveyed patients, the guidelines were correctly implemented. The
      intervention had no measurable negative clinical effect. CONCLUSION: A
      comprehensive, multifaceted educational program for treating urinary and
      respiratory tract infections in the elderly was a safe and practical method to
      change physicians' antibiotic prescribing practice and significantly reduce the
      consumption and costs of antibiotics in a geriatric hospital.

PMID- 14687325
TI  - Sexual healthcare needs of women aged 65 and older.
AB  - OBJECTIVES: To compare prevalence and type of sexual concerns and interest in and
      experience with discussing these concerns with physicians for women younger than
      65 and 65 and older. DESIGN: Cross-sectional survey. SETTING: Departments of
      Family Practice and Obstetrics and Gynecology at Madigan Army Medical Center,
      Tacoma, Washington. PARTICIPANTS: Of 1,480 women seeking routine gynecological
      care, 964 (65%) responded; 163 (17%) were aged 65 and older. MEASUREMENTS: Self
      reported sexual concerns and interest in and experience with discussing these
      concerns with their physicians. RESULTS: Older women had a similar number of
      sexual concerns as younger women and were more likely to be concerned about their
      partner's sexual difficulties. Older women were less likely to have ever had the
      topic of sexual health raised during healthcare visits. Even though these women
      were more likely to report youthful-appearing physicians as hindering the topic
      of sexual health, the majority indicated that they would have discussed their
      concerns had the physician raised the topic and were interested in a follow-up
      appointment to do so. CONCLUSION: Although the types of sexual concerns vary in
      frequency, women aged 65 and older have a similar number of sexual concerns as
      younger women. Older women want physicians to inquire about their sexual health.
      This discussion should include inquiries about their partner's sexual
      functioning. To overcome age as a barrier to this discussion, younger physicians
      should be particularly attentive to initiating the topic of sexual health.

PMID- 14687326
TI  - Agreement between self-report of disease diagnoses and medical record validation
      in disabled older women: factors that modify agreement.
AB  - OBJECTIVES: To determine the agreement between self-report of chronic disease and
      validated evidence of disease using multiple ascertainment methods and to assess
      effects of cognition, education, age, and comorbidity. DESIGN: Cross-sectional
      analysis. SETTING: Community Baltimore, Maryland. PARTICIPANTS: One thousand two
      community-dwelling disabled women aged 65 and older. MEASUREMENTS: Kappa
      statistics were calculated to determine the relationship between self-report of
      14 diseases and standardized algorithms. Analyses were stratified using Mini
      Mental State Examination score, education, number of chronic diseases, and age.
      RESULTS: Kappa was excellent for hip fracture (HF), Parkinson's disease (PD),
      diabetes mellitus (DM), cancer, stroke, and disc disease (DD); fair to good for
      angina pectoris, congestive heart failure, and myocardial infarction; and poor
      for peripheral arterial disease, spinal stenosis, osteoporosis, arthritis, and
      lung disease. Overall, kappa decreased with decreasing cognition and education,
      increasing age, and four or more diseases. CONCLUSION: In disabled older women,
      self-report of physician diagnosis of HF, PD, DM, cancer, stroke, and DD appears
      valid. In general, increasing comorbidity and age and decreasing cognition and
      education do not reduce validity for diseases where agreement was excellent
      overall.

PMID- 14687327
TI  - Reproducibility of the jumping mechanography as a test of mechanical power output
      in physically competent adult and elderly subjects.
AB  - OBJECTIVES: To compare the reproducibility of the newly developed jumping
      mechanography with other physical tests. DESIGN: Study 1: Repeated testing with
      an interval of 2 weeks to assess the short-term repetition error. Study 2:
      Testing on 5 successive days to assess learning effects. SETTING: Geriatric
      clinic, Esslingen, Germany. PARTICIPANTS: Study 1 had 36 subjects aged 24 to 88;
      Study 2 had 22 subjects aged 19 to 86. Locomotor competence in all subjects was
      assessed using the ability to walk unaided and to perform a tandem stand and
      tandem walk. MEASUREMENTS: The test battery consisted of timed up and go, freely
      chosen gait speed, maximum gait speed, chair-rising test, and maximum power in
      jumping mechanography. RESULTS: All subjects performed the jumping mechanography
      without major problems. Study 1: Of all tests, maximum power in jumping
      mechanography depicted the smallest intrasubject short-term error (3.6%), the
      largest intersubject coefficient of variation (45.4%), and the greatest test
      retest correlation coefficient (r=0.99). Study 2: The only tests for which the
      learning effects were confined to the 1% range were the maximum gait speed test
      and the maximum power in jumping mechanography. CONCLUSION: Assessment of maximum
      power in jumping mechanography appears to have good test-retest reliability with
      negligible learning effects. Moreover, it results in a comparatively large
      intersubject variability, which makes it an interesting method in the assessment
      of aging effects in middle-aged to older subjects and patients.

PMID- 14687328
TI  - Underlying mechanisms of impaired visceral pain perception in older people.
AB  - There is increasing recognition that aging can have a profound effect on the
      presentation of illness. Older patients with diseases of visceral organs are much
      more likely than younger adults to present atypically. Examples are the frequent
      absence of pain in older patients with conditions such as myocardial infarction,
      peptic ulcer disease, and pneumothorax. Recent developments have helped elucidate
      the complex processes involved in signaling information from the effects of
      noxious stimuli on visceral organs, but understanding of why older patients with
      visceral disease are more likely to present without pain is still rudimentary.
      Much of the previous experimental evidence on age-related differences relates to
      somatic rather than visceral sources of pain. As a result, it may not have direct
      comparability with transmission of information on visceral damage or noxious
      stimulation. This article reviews the published pathophysiological data on
      sensory transmission from visceral organs. Where possible, this is correlated
      with other published clinical studies on age-related differences in visceral pain
      perception. Areas in which experimental evidence is absent are also highlighted.
      Finally suggestions are made as to how newer experimental and neuroimaging
      techniques may help to increase understanding of this complex subject and its
      resulting clinical applicability.

PMID- 14687329
TI  - Curricular framework: core competencies in multicultural geriatric care.
AB  - Strategies to reduce the documented disparities in health and health care for the
      rapidly growing numbers of older patients from diverse ethnic populations include
      increased cultural competence of providers. To assist geriatric faculty in
      medical and other health professional schools develop cultural competence
      training for their ethnogeriatric programs, the University of California Academic
      Geriatric Resource Program partnered with the Ethnogeriatric Committee of the
      American Geriatrics Society to develop a curricular framework. The framework
      includes core competencies based on the format of the Core Competencies for the
      Care of Older Patients developed by the Education Committee of the American
      Geriatrics Society. Competencies in attitudes, knowledge, and skills for medical
      providers caring for elders from diverse populations are specified. Also included
      are recommended teaching strategies and resources for faculty to pursue the
      development of full curricula.

PMID- 14687330
TI  - Older driver safety: a report from the older drivers project.
AB  - Older driver safety is a growing public health concern for which interventions
      are currently being sought. Statistics show that older drivers suffer a
      disproportionately high rate of motor vehicle fatalities compared with other
      adult drivers. This disproportion is due to two factors: an increased crash rate
      per vehicle mile driven and an increased risk of fatality in the event of a
      crash. Traditionally, traffic safety efforts for the older population have
      focused on methods to identify unsafe drivers to enforce driving cessation, but
      driving cessation deprives the majority of older Americans of their primary form
      of transportation and has been associated with an increase in depressive
      symptoms. In response to these concerns, the Older Drivers Project, created by
      the American Medical Association in partnership with the National Highway Traffic
      Safety Administration, describes and advocates a more acceptable approach to
      traffic safety. The primary objective of this approach involves helping older
      drivers stay on the road safely to preserve their mobility and independence. This
      can be accomplished through three methods: (1) optimizing the driver, (2)
      optimizing the driving environment, and (3) optimizing the vehicle. In this
      approach, driving cessation is recommended only after the safety of the driver
      cannot be secured through any other means.

PMID- 14687331
TI  - The Northern California Chronic Care Network for Dementia.
AB  - The Northern California Chronic Care Network for Dementia brings together
      Northern California's major providers of managed care, community-based care,
      consumer education, and advocacy in new partnerships to improve the care of
      persons with dementia enrolled in managed care plans and their family caregivers.
      These partnerships are part of a national initiative entitled the Chronic Care
      Network for Alzheimer's Disease (CCN/AD) sponsored by the National Chronic Care
      Consortium and the Alzheimer's Association. This initiative selected eight
      promising provider-consumer partnerships across the country to implement and
      evaluate a new model of coordinated care for people with dementia and their
      families. This paper describes the Northern California network's partnerships and
      its intervention and challenges. The intervention is grounded in the key
      components of the CCN/AD model: "identification of patients with possible
      dementia, diagnostic assessment, care management and family caregiver information
      and support." These components, in turn, are translated into protocols and
      pathways designed to create timely, comprehensive, appropriate, and effective
      systems of care services that address the unique needs of dementia patients and
      their caregivers over the course of the disease.

PMID- 14687333
TI  - Do-not-resuscitate orders and hospitalization of nursing home residents:
      trumping, neglect, or shared decision-making at the eleventh hour.

PMID- 14687334
TI  - I am a geriatrician.

PMID- 14687335
TI  - Coping skills.

PMID- 14687336
TI  - Malnutrition and pressure ulcers: data are still incomplete.

PMID- 14687338
TI  - Pressure ulcers: guidelines and data.

PMID- 14687340
TI  - Extensive scalp necrosis and subepicranial abscess in a patient with giant cell
      arteritis.

PMID- 14687341
TI  - Effect of magnetic insoles on balance in older adults.

PMID- 14687342
TI  - Is there a role for pupillometry in the diagnostic approach of Alzheimer's
      disease? a review of the data.

PMID- 14687345
TI  - The effect of group exercise on physical functioning and falls in frail older
      people living in retirement villages: a randomized, controlled trial.
AB  - OBJECTIVES: To determine whether a 12-month program of group exercise can improve
      physical functioning and reduce the rate of falling in frail older people.
      DESIGN: Cluster randomized, controlled trial of 12 months duration. SETTING:
      Retirement villages in Sydney and Wollongong, Australia. PARTICIPANTS: Five
      hundred fifty-one people aged 62 to 95 (mean+/-standard deviation=79.5+/-6.4) who
      were living in self- and intermediate-care retirement villages. MEASUREMENTS:
      Accidental falls, choice stepping reaction time, 6-minute walk distance postural
      sway, leaning balance, simple reaction time, and lower-limb muscle strength.
      RESULTS: Two hundred eighty subjects were randomized to the weight-bearing group
      exercise (GE) intervention that was designed to improve the ability of subjects
      to undertake activities for daily living. Subjects randomized to the control arm
      (n=271) attended flexibility and relaxation (FR) classes (n=90) or did not
      participate in a group activity (n=181). In spite of the reduced precision of
      cluster randomization, there were few differences in the baseline characteristics
      of the GE and combined control (CC) subjects, although the mean age of the GE
      group was higher than that of the CC group, and there were fewer men in the GE
      group. The mean number of classes attended was 39.4+/-28.7 for the GE subjects
      and 31.5+/-25.2 for the FR subjects. After adjusting for age and sex, there were
      22% fewer falls during the trial in the GE group than in the CC group (incident
      rate ratio=0.78, 95% confidence interval (CI)=0.62-0.99), and 31% fewer falls in
      the 173 subjects who had fallen in the past year (incident rate ratio=0.69, 95%
      CI=0.48-0.99). At 6-month retest, the GE group performed significantly better
      than the CC group in tests of choice stepping reaction time, 6-minute walking
      distance, and simple reaction time requiring a hand press. The groups did not
      differ at retest in tests of strength, sway, or leaning balance. CONCLUSION:
      These findings show that group exercise can prevent falls and maintain physical
      functioning in frail older people.

PMID- 14687346
TI  - Intense tai chi exercise training and fall occurrences in older, transitionally
      frail adults: a randomized, controlled trial.
AB  - OBJECTIVES: To determine whether an intense tai chi (TC) exercise program could
      reduce the risk of falls more than a wellness education (WE) program in older
      adults meeting criteria for transitioning to frailty. DESIGN: Randomized,
      controlled trial of 48 weeks duration. SETTING: Twenty congregate living
      facilities in the greater Atlanta area. PARTICIPANTS: Sample of 291 women and 20
      men aged 70 to 97. MEASUREMENTS: Demographics, time to first fall and all
      subsequent falls, functional measures, Sickness Impact Profile, Centers for
      Epidemiologic Studies-Depression Scale, Activities-specific Balance Confidence
      Scale, Falls Efficacy Scales, and adherence to interventions. RESULTS: The risk
      ratio (RR) of falling was not statistically different in the TC group and the WE
      group (RR=0.75, 95% confidence interval (CI)=0.52-1.08), P=.13). Over the 48
      weeks of intervention, 46% (n=132) of the participants did not fall; the
      percentage of participants that fell at least once was 47.6% for the TC group and
      60.3% for the WE group. CONCLUSION: TC did not reduce the RR of falling in
      transitionally frail, older adults, but the direction of effect observed in this
      study, together with positive findings seen previously in more-robust older
      adults, suggests that TC may be clinically important and should be evaluated
      further in this high-risk population.

PMID- 14687347
TI  - Function and back symptoms in older adults.
AB  - OBJECTIVES: To determine the relationship between back symptoms and limitations
      in nine specific functional activities. DESIGN: A cross-sectional study. SETTING:
      This study was conducted as part of the Framingham Heart Study, a population
      based study performed on a representative sample of community-living residents of
      Framingham, Massachusetts. PARTICIPANTS: Subjects consisted of 1,007 surviving
      members of the original cohort who participated in the 22nd Biennial Examination
      in 1992-93. Ages ranged from 70 to 100. MEASUREMENTS: Subjects were asked whether
      they experienced pain, aching, or stiffness in their back on most days and
      whether they had difficulty performing nine specific functional skills. Odds
      ratios (ORs) and confidence intervals are reported for the entire sample and
      within categories of sex. The proportion of functional limitations attributable
      to back symptoms and the proportion of limitations ascribed by subjects to back
      symptoms among subjects with these limitations are also reported. RESULTS: The
      results provide evidence of a relationship between back symptoms and functional
      limitations. ORs were highest for difficulty standing in one place for about 15
      minutes, pushing or pulling a large object, and walking half a mile. Of those
      with back symptoms, 43% to 63% of limitations in activities were due to back
      symptoms. Among all subjects, back symptoms were so prevalent that 18% to 34% of
      all functional limitations were attributable to back symptoms. The association
      between back symptoms and functional limitations was especially strong in women.
      CONCLUSION: Back symptoms account for a large percentage of functional
      limitations in older adults, especially in women.

PMID- 14687348
TI  - Depressive symptoms as a risk factor for disabling back pain in community
      dwelling older persons.
AB  - OBJECTIVES: To determine whether the presence of depressive symptoms is an
      independent risk factor for disabling back pain in community-dwelling older
      persons. DESIGN: Prospective cohort study with a 12-month follow-up period.
      SETTING: General community. PARTICIPANTS: Seven hundred forty-four members of a
      large health plan who were aged 70 and older and independent in bathing, walking,
      dressing, and transferring at baseline. MEASUREMENTS: The presence of depressive
      symptoms, defined as a score of 16 or greater on the Center for Epidemiologic
      Studies-Depression Scale, was documented during a comprehensive baseline
      assessment that also included information regarding participants' demographic,
      medical, and physical/cognitive status. The occurrence of disabling back pain was
      ascertained during monthly telephone interviews. RESULTS: Depressive symptoms
      were present in 153 (20.6%) participants at baseline. Over the 12-month follow-up
      period, 186 participants (25.0%) reported disabling back pain during 1 to 2
      months and 91 (12.2%) during 3 or more months. After adjustment for potential
      confounders, the presence of depressive symptoms was independently associated
      with the occurrence of disabling back pain (adjusted odds ratio (AOR)=2.3 (95%
      confidence interval (CI)=1.2-4.4) for 1 to 2 months with disabling back pain;
      AOR=7.8 (95% CI=3.7-16.4) for 3 or more months with disabling back pain).
      CONCLUSION: The presence of depressive symptoms is a strong, independent, and
      highly prevalent risk factor for the occurrence of disabling back pain in
      community-dwelling older persons.

PMID- 14687350
TI  - Diagnosis-related group-adjusted hospital costs are higher in older medical
      patients with lower functional status.
AB  - OBJECTIVES: To determine whether hospital costs are higher in patients with lower
      functional status at admission, defined as dependence in one or more activities
      of daily living (ADLs), after adjustment for Medicare Diagnosis-Related Group
      (DRG) payments. DESIGN: Prospective study. SETTING: General medical service at a
      teaching hospital. PARTICIPANTS: One thousand six hundred twelve patients aged 70
      and older. MEASUREMENTS: The hospital cost of care for each patient was
      determined using a cost management information system, which allocates all
      hospital costs to individual patients. RESULTS: Hospital costs were higher in
      patients dependent in ADLs on admission than in patients independent in ADLs on
      admission ($5,300 vs $4,060, P<.01). Mean hospital costs remained higher in ADL
      dependent patients than in ADL-independent patients in an analysis that adjusted
      for DRG weight ($5,240 vs $4,140, P<.01), and in multivariate analyses adjusting
      for age, race, sex, Charlson comorbidity score, acute physiology and chronic
      health evaluation score, and admission from a nursing home as well as for DRG
      weight ($5,200 vs $4,220, P<.01). This difference represents a 23% (95%
      confidence interval=15-32%) higher cost to take care of older dependent patients.
      CONCLUSION: Hospital cost is higher in patients with worse ADL function, even
      after adjusting for DRG payments. If this finding is true in other hospitals, DRG
      based payments provide hospitals a financial incentive to avoid patients
      dependent in ADLs and disadvantage hospitals with more patients dependent in
      ADLs.

PMID- 14687351
TI  - Age and features of movement influence motor overflow.
AB  - OBJECTIVES: To measure the magnitude and prevalence of motor overflow to the arm
      at rest during attempted unilateral arm movements. DESIGN: Cross-sectional
      assessment. SETTING: Motor physiology laboratory. PARTICIPANTS: Healthy young
      (n=20) and elderly (n=20) adult subjects. MEASUREMENTS: Surface electromyography
      (EMG) was obtained from bilateral forearm muscles during performance of 12
      different unilateral finger-tapping tasks. RESULTS: For all subjects, faster
      movement rate (F=2.56-3.30, P<.05), cognitive distraction (F=4.09, P<.05), and
      fatigue (F=15.15, P<.001) were each associated with a significant increase in the
      magnitude of EMG in the arm intended to be at rest. In elderly subjects, tapping
      at maximum rate and fatigue were each associated with a further increase in motor
      overflow across the midline. In addition, better left hand dexterity correlated
      with greater motor overflow to the right hand during rapid left hand tapping
      (r=0.63, P<.005). Prevalence of motor overflow was also higher in older subjects
      for some tasks, for example during 1 Hz tapping by the right index finger (motor
      overflow present in 45%, vs 15% young subjects, P<.05). CONCLUSION: Several
      behavioral variables increase motor overflow across the midline in young and
      elderly adults. Motor overflow was even greater in elderly subjects with the most
      demanding tasks and was greater in those with better motor status, suggesting
      that this form of motor system change is a compensatory event of normal aging
      rather than age-related dysfunction. The results support the hypotheses that
      healthy aging is associated with an increase in the degree to which brain
      function is bilaterally organized.

PMID- 14687349
TI  - Diagnosis and treatment of depression in the elderly medicare population:
      predictors, disparities, and trends.
AB  - OBJECTIVES: To develop nationally representative estimates of rates of diagnosis
      of depression; to determine rates and type of treatment received by those
      diagnosed with depression; and to ascertain socioeconomic differences and trends
      in treatment rates of depression, including the effect of supplemental insurance
      coverage, for elderly Medicare fee-for-service beneficiaries. DESIGN: Analysis of
      merged interview and Medicare claims data for multiple years from merged Medicare
      claims and interview data from the Medicare Current Beneficiary Survey (MCBS), a
      nationally representative survey of Medicare participants. SETTING: Community
      dwellers. PARTICIPANTS: Twenty thousand nine hundred sixty-six community-dwelling
      respondents aged 65 and older in the MCBS cost and use files for 1992 through
      1998. MEASUREMENTS: Diagnoses recorded in Medicare claims were used to identify
      individuals who received a diagnosis of depression from a healthcare provider;
      pharmacy and claims data were used to identify receipt of antidepressants and
      psychotherapy by those diagnosed. RESULTS: The rate of depression diagnosis more
      than doubled, reaching 5.8% in 1998. Overall, about two-thirds of those diagnosed
      received treatment in each year; but those aged 75 and older, those of "Hispanic
      or other" ethnicity, and those without additional coverage to supplement Medicare
      were significantly less likely to receive treatment, controlling for other
      characteristics. If treated, members of these disadvantaged subgroups were less
      likely to receive psychotherapy. CONCLUSION: Although depression has been thought
      until recent years to be underrecognized in the elderly, rates of diagnosis
      increased dramatically in the 1990s, with concomitant increases in treatment.
      Nevertheless, significant disparities by age, ethnicity, and supplemental
      insurance coverage persist in treatment of those diagnosed. Because depression is
      a major source of potentially treatable morbidity in older people, increased
      efforts are needed to ensure access to appropriate treatment across all subgroups
      of older people and to remove economic barriers to treatment.

PMID- 14687352
TI  - Intentional and unintentional weight loss increase bone loss and hip fracture
      risk in older women.
AB  - OBJECTIVES: To test the hypothesis that unintentional weight loss increases the
      rate of bone loss and risk of hip fracture more than intentional weight loss.
      DESIGN: Prospective cohort study. SETTING: Four communities within the United
      States. PARTICIPANTS: Six thousand seven hundred eighty-five elderly white women
      with measurement of weight change and assessment of intention to lose weight.
      MEASUREMENTS: Weight change between baseline and fourth examinations (average 5.7
      years between examinations) and assessment of intention to lose weight. Weight
      loss was defined as a decrease of 5% or more from baseline weight, stable weight
      was defined as less than a 5% change from baseline weight, and weight gain was
      defined as an increase of 5% or more from baseline weight. Rate of change in bone
      mineral density at the hip between fourth and sixth examinations (average 4.4
      years between examinations) was measured using dual-energy x-ray absorptiometry.
      Incident hip fractures occurring after the fourth examination until June 1, 2001
      (average follow-up 6.6 years) was confirmed using radiographic reports. RESULTS:
      The adjusted average rate of decline in total hipbone density steadily increased
      from -0.52% per year in women with weight gain to -0.68% per year in women with
      stable weight to -0.92% per year in women with weight loss (P-value for trend
      <.001). Higher rates of hip-bone loss were observed in women with weight loss
      irrespective of body mass index (BMI) or intention to lose weight. During follow
      up of an average 6.6 years after the fourth examination, 400 (6%) of the cohort
      suffered a first hip fracture. Women with weight loss had 1.8 times the risk (95%
      confidence interval (CI)=1.43-2.24) of subsequent hip fracture as those with
      stable or increasing weight. The association between weight loss and increased
      risk of hip fracture was consistent across categories of BMI and intention to
      lose weight. Even voluntary weight loss in overweight women with a BMI of 25.9
      kg/m2 (median) or greater increased the risk of hip fracture (multivariate hazard
      ratio=2.48, 95% CI=1.33-4.62). CONCLUSION: Older women who experience weight loss
      in later years have increased rates of hip-bone loss and a two-fold greater risk
      of subsequent hip fracture, irrespective of current weight or intention to lose
      weight. These findings indicate that even voluntary weight loss in overweight
      elderly women increases hip fracture risk.

PMID- 14687353
TI  - Antidiabetic drug therapy of African-American and white community-dwelling
      elderly over a 10-year period.
AB  - OBJECTIVES: To determine the prevalence and predictors of antidiabetic medication
      use over a 10-year period in a general population of African-American and white
      community-dwelling elderly. DESIGN: Survey. SETTING: Five adjacent counties (one
      urban and four rural) in the Piedmont area of North Carolina. PARTICIPANTS: Those
      aged 65 and older present at the baseline (n=4,136), second (n=3,234), third
      (n=2,508), and fourth (n=1,633) in-person waves of the Duke Established
      Populations for Epidemiologic Studies of the Elderly. MEASUREMENTS: The use of
      six discrete categories of antidiabetic medications (insulin, first-generation
      oral sulfonylureas, second-generation oral sulfonylureas, metformin, oral
      combination therapy, and insulin combination therapy) was determined.
      Multivariate analyses, using weighted data adjusted for sampling design, were
      conducted to assess the association between antidiabetic medication use and race
      and other sociodemographic, health-status, and access-to-healthcare factors at
      baseline and 10 years later. RESULTS: Antidiabetic medications were taken by
      21.4% of the population at baseline; this increased to 28.1% at the 10-year
      follow-up (P<.001). Insulin was the most commonly used drug at baseline (7.9%).
      The use of second-generation sulfonylureas increased, and use of first-generation
      sulfonylureas decreased over the 10-year time period. Combination antidiabetic
      therapy and metformin use was infrequent throughout the study. Multivariate
      analyses revealed that, at baseline, African Americans were nearly twice as
      likely (adjusted odds ratio (AOR)=1.93, 95% confidence interval (CI)=1.46-2.54)
      to receive any antidiabetic medication as their white counterparts. Other
      significant (P<.05) factors were hypertension (AOR=1.38, 95% CI=1.03-1.84),
      stroke (AOR=1.98, 95% CI=1.43-2.73), one or more mobility difficulties (AOR=1.29,
      95% CI=1.01-1.66), continuity of care (AOR=1.74, 95% CI=1.20-2.54), and multiple
      doctor visits (1-4 visits, AOR=1.69, 95% CI=1.08-2.65; >/=5 visits, AOR=3.15, 95%
      CI=1.95-5.07). Being underweight (AOR=0.45, 95% CI=0.30-0.67) and being
      cognitively impaired (AOR=0.60, 95% CI=0.41-0.87) were factors significantly
      (P<.05) associated with a decreased risk of antidiabetic medication use. At the
      10-year follow-up, similar trends were seen associating these sociodemographic,
      health-status, and access-to-healthcare factors with antidiabetic medication use.
      CONCLUSION: Antidiabetic medication use is common and increases over time for
      community-dwelling elderly. Race is significantly associated with antidiabetic
      medication use, even after controlling for other sociodemographic, health-status,
      and access-to-healthcare variables.

PMID- 14687354
TI  - A standardized quality assessment system to evaluate incontinence care in the
      nursing home.
AB  - OBJECTIVES: To demonstrate the reliability and feasibility of a standardized
      protocol to assess and score urinary incontinence care in nursing homes. DESIGN:
      Descriptive. SETTING: Eighteen nursing homes (NHs). PARTICIPANTS: Four hundred
      twenty-six incontinent residents. MEASUREMENTS: Resident interview data were used
      to score three quality indicators, and usable data were retrieved from 117 (27%)
      of 426 incontinent residents in 18 homes who were selected for interview based on
      evidence that they could accurately describe the care they received. Medical
      record data were used to score six quality indicators for a subset of 58
      participants in five homes. RESULTS: Zero to 98% of the participants were scored
      as receiving care consistent with the intent of the indicator across the nine
      indicators. All NHs failed to provide chart documentation of an assessment to
      determine an incontinent resident's appropriateness for a scheduled toileting
      program (0% passed). The absence of an assessment to determine a resident's
      potential responsiveness to toileting assistance may explain why 103 incontinent
      residents who were documented on the Minimum Data Set as being on a scheduled
      toileting program reported that they received the same number of toileting
      assists per day (1.3) as the group of 114 incontinent residents who were not on a
      scheduled toileting program (1.0). The received toileting assistance frequencies
      reported by both groups were too low to maintain continence. CONCLUSION: The
      standardized quality assessment system generated scores for nine incontinence
      quality indicators with good interrater reliability and provided explicit scoring
      rules that can facilitate replication. The focus of the indicators on care
      processes that are under the control of NH staff make the protocol useful for
      external survey and internal quality improvement purposes.

PMID- 14687355
TI  - Effects of vitamin D supplementation on strength, physical function, and health
      perception in older, community-dwelling men.
AB  - OBJECTIVES: To study the effects of vitamin D supplementation in healthier
      populations of men. DESIGN: : Randomized, controlled trial. SETTING: General
      clinical research center. PARTICIPANTS: Sixty-five healthy, community-dwelling
      men (mean age+/-standard deviation=76+/-4, range 65-87). INTERVENTION:
      Cholecalciferol (1,000 IU/d) or placebo supplementation for 6 months; all
      received 500 mg supplemental calcium. MEASUREMENTS: Upper and lower extremity
      muscle strength and power, physical performance and activity, health perception,
      calcium and vitamin D intake, and biochemical assessment, including 25
      hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and ionized calcium levels.
      RESULTS: The levels of 25OHD increased and PTH decreased in the cholecalciferol
      group, whereas there were no significant changes in the control group (P<.001).
      Baseline 25OHD levels correlated with baseline single-leg stance time and
      physical activity score. Baseline PTH levels correlated with baseline 8-foot walk
      time and physical activity score. No significant difference in strength, power,
      physical performance, or health perception was found between groups. CONCLUSION:
      The 25OHD or PTH levels correlated with physical activity and physical
      performance in older, community-dwelling men with normal 25OHD status. Vitamin D
      supplementation increased 25OHD levels and decreased PTH levels but did not
      increase muscle strength or improve physical performance or health perception in
      this group of healthy, older men. Further investigations of the effects of
      vitamin D supplementation should focus on individuals with low levels of vitamin
      D.

PMID- 14687356
TI  - Alternative therapy use by elderly African Americans attending a community
      clinic.
AB  - OBJECTIVES: To describe the use of orally ingested alternative therapies (OAT) by
      a community-dwelling, primarily African-American sample of elders. DESIGN: Face
      to-face survey. SETTING: University-affiliated geriatric medicine primary care
      clinic. PARTICIPANTS: One hundred two elderly OAT users and 100 nonusers who had
      an appointment between June and August 2000. MEASUREMENTS: Demographic
      characteristics, OAT products used, reasons for use, and influencing factors
      leading to use. RESULTS: Two hundred ninety-two subjects were screened: 102 (35%)
      OAT users, 100 (34%) nonusers, and 90 (31%) who refused to participate. The OAT
      users were 78% female and 67% African American, with a mean age+/-standard
      deviation of 79.7+/-6.2. They were a frail group, with an average of 5.2+/-2.3
      medical conditions, 4.5+/-2.3 medications, and 52% with at least one impairment
      in activities of daily living. Nonusers had more documented medical conditions
      and medications and a lower median household income. The most popular OAT
      products were multivitamins (65%), vitamin E (42%), and calcium (31%). Ninety
      seven percent of users reported concurrent OAT and prescription medication use.
      The patients took OATs to supplement their diet (23%) and stay well (15%), as
      well as for various medical conditions. Influencing factors for OAT use were
      media advertisements (37%), physicians' advice (36%), and immediate family
      members (19%). Sixty percent of elders discussed their OAT use with their
      physicians CONCLUSION: Community-dwelling, primarily African-American, elders are
      using OATs despite physical frailty and limited financial resources. OAT users
      are healthier and wealthier than nonusers. More subjects used concurrent OAT and
      prescription medications and discussed their use with their physicians than would
      be expected from the literature. A large national survey of OAT use by minority
      elders could explore these findings.

PMID- 14687357
TI  - Psychiatric morbidity in a neurology-based memory clinic: the effect of
      systematic psychiatric evaluation.
AB  - OBJECTIVES: To estimate the prevalence of psychiatric morbidity and the effect of
      systematic psychiatric evaluation in patients referred to a memory clinic in a
      neurological setting. DESIGN: Descriptive case-series study in consecutive
      referrals to a memory clinic. SETTING: An outpatient multidisciplinary memory
      clinic in a neurological setting. PARTICIPANTS: An index group of 100 consecutive
      patients (aged 60-89) referred for diagnostic evaluation of cognitive symptoms
      during a period of 8 months and a reference group of 686 consecutive patients
      (aged 60-98) referred during a previous period of 54 months. In the index group,
      a systematic psychiatric evaluation was performed in addition to the neurological
      evaluation and routine investigations. In the reference group, patients had the
      same basic evaluation, but psychiatric evaluation was optional and was performed
      in 21% of the patients. MEASUREMENTS: Prevalence of primary psychiatric morbidity
      in the index and reference groups according to international clinical criteria
      and multidisciplinary consensus report and three key psychiatric symptoms:
      delusions, hallucinations, and affective symptoms in the index group. RESULTS:
      Twenty-three percent of patients in the index group had a primary psychiatric
      disease. A primary psychiatric disease was diagnosed in 8% of patients in the
      reference group (P<.001). One or more psychiatric symptoms were identified in 72%
      of all patients in the index group. CONCLUSION: Psychiatric conditions and
      symptoms are frequent in elderly patients with cognitive symptoms, including
      those referred to a neurological memory clinic. The data provide evidence for a
      multispecialty and multidisciplinary approach to the diagnosis and management of
      patients with possible dementia.

PMID- 14687358
TI  - Use of the Agency for Health Care Policy and Research Urinary Incontinence
      Guideline in nursing homes.
AB  - The objective of this study was to assess the use of the Agency for Health Care
      Policy and Research (now called the Agency for Healthcare Research and Quality)
      Urinary Incontinence (UI) Guideline (1996) in nursing homes (NHs) using
      retrospective chart review and nursing assistant screening interviews. The study
      was conducted in a nonrandom sample of 52 NHs in upstate New York. Two hundred
      residents developing new UI or newly admitted with UI on the dayshift and who met
      criteria for evaluation and treatment/management were evaluated in the 12 weeks
      after onset of or admission with UI. Fifteen percent of newly admitted residents
      needed evaluation. Of residents already in NHs, 2.3 per 100 beds developed new UI
      over the 12 weeks. Aspects of UI evaluation rarely done were rectal examination
      (15%), digital examination of prostate (15%), and pelvic examination (2%). Sixty
      eight percent had a culture/sensitivity, 56% a urinalysis, and 6% a postvoid
      residual. Eighty-one percent had a reversible cause at the time of onset, but
      only 34% had all addressed. Few (2%) needed urologist evaluation. Treatment was
      rare (3%), but management using toileting and absorbent products were common.
      Only 6% achieved resolution of UI. These results suggest that assessment and
      treatment of UI is manageable (a total of 4.2 new cases per 100 beds per 12
      weeks) but quality is not adequate. On average, only 20% of the standards
      applicable were met, due primarily to lack of awareness of new UI and lack of
      familiarity with the guideline. Thus, improvements are needed. Recommendations
      for guideline revision are made.

PMID- 14687359
TI  - Restructuring primary care practices to manage geriatric syndromes: the ACOVE-2
      intervention.
AB  - Despite evidence suggesting that primary care physicians do not address geriatric
      conditions adequately in practice, most efforts to change physicians' practice
      behaviors have been ineffective or too expensive to implement and sustain. In its
      second phase, the Assessing Care of the Vulnerable Elders (ACOVE-2) project has
      developed an intervention aimed at improving the care that primary care
      physicians provide for three geriatric conditions-falls, urinary incontinence,
      and cognitive impairment/dementia. The intervention addresses specific processes
      of care identified in the first phase of the ACOVE project (ACOVE-1) as important
      to the care of community-dwelling older persons. Beginning with case finding, the
      intervention uses a standardized multicomponent practice-change effort. The
      condition-specific intervention employs four methods of changing medical
      practice: efficient collection of condition-specific clinical data, medical
      record prompts to encourage performance of essential care processes, patient
      education materials and activation of the patient's role in follow-up, and
      physician decision support and physician education. Moreover, the costs of the
      intervention are low. The effectiveness of the intervention in improving the
      processes of care for these conditions and clinical outcomes will need to be
      evaluated in controlled trials.

PMID- 14687360
TI  - Selected as the best paper in the 1990s: Reducing frailty and falls in older
      persons: an investigation of tai chi and computerized balance training.
AB  - OBJECTIVES: To evaluate the effects of two exercise approaches, tai chi (TC) and
      computerized balance training (BT), on specified primary outcomes (biomedical,
      functional, and psychosocial indicators of frailty) and secondary outcomes
      (occurrences of fall). DESIGN: The Atlanta Frailty and Injuries: Cooperative
      Studies and Intervention Techniques, a prospective, randomized, controlled
      clinical trial with three arms (TC, BT, and education (ED)). Intervention length
      was 15 weeks, with primary outcomes measured before and after intervention and at
      4-month follow-up. Falls were monitored continuously throughout the study.
      SETTING: Persons aged 70 and older living in the community. PARTICIPANTS: A total
      of 200 participants, 162 women and 38 men; mean age was 76.2. MEASUREMENTS:
      Biomedical (strength, flexibility, cardiovascular endurance, body composition),
      functional instrumental activities of daily living (IADL), and psychosocial well
      being (Center for Epidemiological Studies for Depression scale, fear of falling
      questionnaire, self-perception of present and future health, mastery index,
      perceived quality of sleep, and intrusiveness) variables. RESULTS: Grip strength
      declined in all groups, and lower extremity range of motion showed limited but
      statistically significant changes. Lowered blood pressure before and after a 12
      minute walk was seen following TC participation. Fear of falling responses and
      intrusiveness responses were reduced after the TC intervention compared with the
      ED group (P=.046 and P=.058, respectively). After adjusting for fall risk
      factors, TC was found to reduce the risk of multiple falls by 47.5%. CONCLUSION:
      A moderate TC intervention can impact favorably on defined biomedical and
      psychosocial indices of frailty. This intervention can also have favorable
      effects upon the occurrence of falls. TC warrants further study as an exercise
      treatment to improve the health of older people.

PMID- 14687361
TI  - Tai chi, falls, and the heritage of JAGS.

PMID- 14687362
TI  - Managing atrial fibrillation in older people: a comparison of two treatment
      strategies.

PMID- 14687363
TI  - Inequities in depression management in low-income, minority, and old-old adults:
      a matter of access to preferred treatments?

PMID- 14687364
TI  - Quality of incontinence management in U.S. nursing homes: a failing grade.

PMID- 14687365
TI  - Sherlock Holmes at the bedside: the case of the missing patient.

PMID- 14687366
TI  - Emotional vitality and change in lower extremity function after acute medical
      illness and hospitalization.

PMID- 14687367
TI  - Cabergoline and silent aspiration in elderly patients with stroke.

PMID- 14687368
TI  - Cancer in the elderly: to screen or not to screen?

PMID- 14687370
TI  - Caregiving and age: the case of a very old sister of a patient with Alzheimer's
      disease.

PMID- 14687371
TI  - Role of chronic sinusitis in cognitive functioning in the elderly.

PMID- 14687372
TI  - Use of antibacterial drugs in community-dwelling older persons.

PMID- 14687373
TI  - Ignoring the controversies: newspaper reports on Alzheimer's disease treatments.

PMID- 14687374
TI  - Paresthesias developing in an elderly patient after chronic usage of
      nitrofurantoin and vitamin B6.

PMID- 14687375
TI  - Subclavian vein occlusion due to pace-maker leads.

PMID- 14687379
TI  - Invasive pneumococcal disease in older adults residing in long-term care
      facilities and in the community.
AB  - OBJECTIVES: To examine the epidemiology of invasive pneumococcal disease in older
      adults hospitalized for invasive pneumococcal disease who are living in the
      community and in long-term care facilities (LTCFs) in the United States. DESIGN:
      Analysis of 2402 cases of invasive pneumococcal disease requiring hospitalization
      in 2000 and 2001 that the Centers for Disease Control and Prevention's Active
      Bacterial Core Surveillance collected in nine states. SETTING: Hospital.
      PARTICIPANTS: Hospitalized LTCF residents and community-living older adults in
      the United States. MEASUREMENTS: Age- and residence-specific pneumococcal disease
      incidence rates per 100000 persons, case-fatality rates, and trends in
      antimicrobial resistance. RESULTS: Nationally, the rate of invasive pneumococcal
      disease in LTCF residents was 194.2 cases per 100000 persons aged 65 and older
      and 44.6 for community-living older adults (relative risk=4.4, 95% confidence
      interval (CI)=4.2-4.5). Compared with community-living older adults, case
      fatality rates were 1.9 times higher (30.8% vs 16.0%, 95% CI=1.5-2.5).
      Pneumococcal strains from LTCF residents were significantly more likely to be
      nonsusceptible to levofloxacin than strains from community- living older adults
      (5.7% vs 0.4%, P<.001). CONCLUSION: Older adults living in LTCFs are at a higher
      risk for invasive pneumococcal disease and death than are community-living older
      adults. Additionally, fluoroquinolone resistance is significantly higher in older
      adults living in LTCFs and may provide clues to emerging antimicrobial resistance
      in the general population.

PMID- 14687380
TI  - Ertapenem therapy for community-acquired pneumonia in the elderly.
AB  - OBJECTIVES: To compare the efficacy and safety of ertapenem, 1 g once a day, with
      ceftriaxone, 1 g once a day, for treatment of the subgroup of patients aged 65
      and older with community-acquired pneumonia (CAP) requiring parenteral therapy.
      DESIGN: Combined data from patients aged 65 and older in two randomized, double
      blind clinical trials. SETTING: Eighty international centers. PARTICIPANTS: Eight
      hundred fifty-seven treated patients, of whom 351 were aged 65 and older.
      INTERVENTIONS: Intravenous or intramuscular ertapenem or ceftriaxone with the
      option to switch to oral amoxicillin-clavulanate after at least 3 days of
      parenteral therapy. MEASUREMENTS: Clinical efficacy was assessed at completion of
      parenteral therapy and 7 to 14 days after all therapy had been completed (test of
      cure (TOC) assessment). Bacterial eradication was assessed at the TOC visit.
      Safety was assessed daily during study therapy and for 14 days thereafter.
      RESULTS: One hundred forty-eight clinically evaluable patients aged 65 and older
      were treated with ertapenem and 125 with ceftriaxone. Pathogens were identified
      in 157 (57.5%) patients (the most common being Streptococcus pneumoniae), most of
      which were penicillin-susceptible. Clinical cure rates were 95.9% for patients in
      the ertapenem group and 92.7% for patients in the ceftriaxone group at completion
      of parenteral therapy and 93.9% and 90.4%, respectively, at the TOC assessment.
      Overall bacterial eradication rates were 92.8% (77 of 83) for patients treated
      with ertapenem and 93.2% (69 of 74) for those treated with ceftriaxone. The most
      common drug-related adverse experiences in both treatment groups were diarrhea
      and mild to moderate elevation of serum aminotransferase levels. CONCLUSION:
      Ertapenem 1 g once a day was highly effective for treatment of elderly patients
      with CAP requiring parenteral therapy and was as effective as ceftriaxone.
      Ertapenem was generally well tolerated, with an overall safety profile similar to
      ceftriaxone.

PMID- 14687381
TI  - Serum vitamin D and falls in older women in residential care in Australia.
AB  - OBJECTIVES: To determine the prevalence of vitamin D deficiency in older people
      in residential care and the influence that the level of vitamin D may have on
      their incidence of falls. DESIGN: Prospective cohort. SETTING: Residential care
      facilities for older people in several states of Australia. PARTICIPANTS: Six
      hundred sixty-seven women in low-level care and 952 women in high-level care,
      mean age 83.7 years. MEASUREMENTS: Serum 25-hydroxyvitamin D (25D) levels and
      recognized risk factors for falls including current medication use, a history of
      previous fractures, weight, tibial length (as a surrogate for height), cognitive
      function, walking ability, and frequency of going outdoors were determined. The
      women in low-level care and high-level care were followed for an average of 145
      and 168 days, respectively. Falls were recorded prospectively in diaries
      completed monthly by residential care staff. RESULTS: Vitamin D deficiency
      (defined as a serum 25D level below 25 nmol/L) was present in 144 (22%) women in
      low-level care and 428 (45%) in high-level care. After excluding 358 bed-bound
      residents and adjusting for weight, cognitive status, psychotropic drug use,
      previous Colles fracture, and the presence of wandering behavior, log serum 25D
      level remained independently associated with time to first fall. The adjusted
      hazards ratio was 0.74 (95% confidence interval=0.59-0.94; P=.01), implying a 20%
      reduction in the risk of falling with a doubling of the vitamin D level.
      CONCLUSION: Vitamin D deficiency is common in residential care in Australia. A
      low level of serum vitamin D is an independent predictor of incident falls.

PMID- 14687382
TI  - Does delirium increase hospital stay?
AB  - OBJECTIVES: To determine the effects of prevalent and incident delirium on length
      of hospital stay. DESIGN: Prospective cohort study, comparing (1). length of stay
      after admission in cases of prevalent delirium versus controls without prevalent
      delirium with (2). length of stay after diagnosis in cases of incident delirium
      versus controls matched by day of diagnosis. SETTING: The medical services of a
      primary, acute care hospital. PARTICIPANTS: Medical admissions of patients aged
      65 and older from the emergency department with delirium diagnosed during the
      first week in hospital. Patients admitted to intensive care or oncology and those
      with a primary diagnosis of stroke were excluded. A sample of those without
      delirium was also enrolled. MEASUREMENTS: Delirium was diagnosed using the
      Confusion Assessment Method. Data on length of stay and diagnosis-related groups
      (DRGs) were abstracted from administrative data. Measures of covariates included
      the Informant Questionnaire on Cognitive Decline in the Elderly, the Delirium
      Index, the instrumental activities of daily living questionnaire from the Older
      American Resources and Services project, the Charlson Comorbidity Index, the
      Clinical Severity Scale, and the Acute Physiology Score. RESULTS: The study
      sample comprised 359 patients: 204 with prevalent delirium, 37 with incident
      delirium, and 118 without delirium. After controlling for covariates, prevalent
      delirium was not associated with a significantly longer hospital stay, but
      incident delirium was associated with an excess stay after diagnosis of 7.78 days
      (95% confidence interval=3.07, 12.48). Similar results were obtained using log
      transformed or DRG-adjusted estimates of length of stay. CONCLUSION: In older
      medical inpatients, incident but not prevalent delirium is an important predictor
      of longer hospital stay. Interventions to prevent incident delirium may reduce
      length of stay.

PMID- 14687383
TI  - Age, vascular risk, and cognitive decline in an older, British, African-Caribbean
      population.
AB  - OBJECTIVES: To investigate associations between baseline factors and subsequent
      cognitive decline in an older African-Caribbean population. DESIGN: Three-year
      follow-up of a community sample. SETTING: Registration lists for seven primary
      care services in south London, United Kingdom. PARTICIPANTS: Of 290 Caribbean
      born people aged 55 to 75 recruited at baseline, 216 (75%) were reinterviewed
      after a 3-year period. Sufficient data for analysis were present for 207.
      MEASUREMENTS: Tests of verbal memory (immediate and delayed), orientation, and
      attention were administered at baseline and at 3 years. A composite measure of
      cognitive change was derived through factor analysis. Participants in the lowest
      quintile were defined as having cognitive decline and were compared with the rest
      of the sample with respect to baseline characteristics. RESULTS: Cognitive
      decline was strongly associated with increased age, but not with sex, education,
      or occupation. It was also not directly associated with hypertension, diabetes
      mellitus, or exercise, but the age-decline association was significantly stronger
      in people with diabetes mellitus and was lower in those reporting vigorous
      physical exercise at baseline. When cognitive decline was investigated separately
      for individual tests, both these patterns of association were particularly strong
      for decline in delayed verbal recall. CONCLUSION: The association between
      increased age and cognitive decline, particularly decline in verbal recall, was
      stronger in people with diabetes mellitus (but not hypertension) and weaker in
      people who were more physically active.

PMID- 14687384
TI  - Treatment of elderly and other adult patients for depression in primary care.
AB  - OBJECTIVES: To determine whether depression is treated differently in older and
      younger patients in primary care clinics. DESIGN: Administrative data were used
      to identify patients with a depression diagnosis code. The sources of data were
      baseline and 3-month follow-up surveys, the health plan electronic database, and
      chart audits. SETTING: Nine primary care clinics owned by a health maintenance
      organization in the Midwest. PARTICIPANTS: The study sample (N=1023) consisted of
      adult patients, aged 19 to 93, and was divided into six age groups, from young
      adult, under age 35, to old old, 75 or older. MEASUREMENTS: Independent variables
      were a series of dummy variables: age groups, baseline depression severity, sex,
      and incident depression. Outcomes were defined as care processes (assessment,
      resources) and improvement in depression symptoms (Center for Epidemiologic
      Studies-Depression scale short form). Univariate and multivariate logistic
      regression analyses were used to analyze patient characteristics, depression
      symptoms, and care process variables. Significance level was reported based on
      the chi-square test of probability, P<or=.05. RESULTS: The adjusted response
      rates to the baseline and follow-up surveys were 69% and 82%. Elderly depressed
      patients were more likely than younger depressed patients to be widowed, have low
      levels of education, have fair or poor health, and have three or more comorbid
      health problems. There were no differences, by age, in number of depressive
      symptoms, antidepressant treatment, or recommendation for a follow-up
      appointment. Younger patients were more likely than older patients to have a new
      diagnosis of depression and to report being depressed most of the past year.
      Providers were only 6% as likely to ask old-old depressed patients about suicide
      risk, about one-fourth as likely to referral them to a mental health therapist,
      about one-fifth as likely to ask if they felt depressed, and one-twentieth as
      likely to ask about a problem with alcohol as they were with young-adult
      depressed patients. The old-old were about one-third as likely to report
      improvement in depression symptoms after 3 months as the young-adult patients.
      CONCLUSION: This study suggests a possible pattern of underattention to the
      oldest depressed patients. Failure to ask about suicide risk is especially of
      concern because of the high suicide rate of depressed geriatric patients. The
      finding that physicians are less likely to focus on depression with old-old
      patients may be explained, in part, by the concept of invisibility of the
      ordinary.

PMID- 14687385
TI  - Benzodiazepine use and physical performance in community-dwelling older women.
AB  - OBJECTIVES: To determine whether benzodiazepine use in older women increased the
      risk of decline in physical function. DESIGN: A four-year prospective cohort
      study. SETTING: The communities of Iowa and Washington counties, Iowa.
      PARTICIPANTS: Eight hundred eighty-five women aged 70 and older who had completed
      physical performance tests in 1988 and 1992. MEASUREMENTS: Benzodiazepine use was
      determined during in-home interviews and classified by dose, duration, indication
      for use, and half-life. Physical performance tests included an assessment of
      standing balance, walking speed (8-foot distance), and repeated chair raises.
      RESULTS: Ninety (10.2%) reported benzodiazepine use at baseline. After adjustment
      for baseline physical performance score and potential confounders, benzodiazepine
      use was associated with a greater decline in physical performance over 4 years
      than nonuse (beta=-1.16; standard error (SE)=0.25; P<.001). The use of higher
      than-recommended dose was related to decline (beta=-2.26; SE=0.47; P<.001), and
      use of lower doses was not (beta=-0.53; SE=0.46; P=.246). Long-term use (>or=3
      years) was related to decline (beta=-1.65; SE=0.34; P<.001), whereas recent and
      past use were not. Similar results were obtained when restricting the sample to
      those without disability at baseline. CONCLUSION: This study provides evidence
      that older women who used benzodiazepines were at risk for decline in physical
      performance. Subgroup analyses indicated that risk was greater with use of higher
      than-recommended doses or for long duration (>or=3 years). These findings
      highlight the importance of using benzodiazepines at the lowest effective dose
      for a limited duration in older women.

PMID- 14687386
TI  - Are nursing homes appropriate for older adults with severe mental illness?
      Conflicting consumer and clinician views and implications for the Olmstead
      decision.
AB  - OBJECTIVES: In response to the recent Olmstead decision, to compare consumer and
      clinician perspectives on the appropriateness of nursing home settings for older
      adults with severe mental illness (SMI) in relation to clinical characteristics
      and care needs. DESIGN: Cross-sectional, descriptive, correlational study.
      SETTING: Ten community mental health centers and two state-funded nursing homes
      specializing in long-term care for older persons with SMI. PARTICIPANTS:
      Consumers of mental health services in the community (n=115) and in nursing homes
      (n=106), aged 60 and older, with SMI. Sixty-four clinicians (51% registered
      nurses, 29% masters-level clinicians, and 20% certified social workers) conducted
      ratings. MEASUREMENTS: Consumers and their clinicians were independently asked to
      determine the most appropriate care setting for each consumer based on care needs
      from three alternatives: nursing home, congregate (group) living setting, or
      individual apartment/home. Clinical characteristics of participants with SMI were
      rated using the Mini-Mental State Examination, Brief Psychiatric Rating Scale,
      Specific Level of Function Scale, Cumulative Illness Rating Scale for Geriatrics,
      a modified memory and orientation subscale from the Clinical Dementia Rating
      Scale, and an item from the Minimum Data Set related to reasoning. RESULTS: Of
      nursing home residents with SMI who did not have severe cognitive impairment, 40%
      (n=42) and 51% (n=54) were considered by consumers or by their clinician,
      respectively, to be more appropriate for a community-based setting, but there was
      a low level of agreement (only 27.6%; no better than chance) between consumers
      and clinicians on which nursing home residents were most appropriate for living
      in the community. Determinations by clinicians were associated with clinical need
      (diagnosis and less-severe behavioral problems), whereas there was no association
      between clinical needs and level of care determinations by consumers. Finally,
      clinicians considered a group home necessary for 93.7% of nursing home residents
      judged to be more appropriate for a community-based setting, whereas 90.5% of
      consumers stated that an apartment or individual home was indicated. CONCLUSION:
      State implementation of the Olmstead decision will need to consider major
      differences in perspectives between clinicians and consumers on the most
      appropriate long-term care setting for older persons with SMI.

PMID- 14687387
TI  - Prevalence and severity of urinary incontinence in elderly Mexican-American
      women.
AB  - OBJECTIVES: To measure prevalence and characteristics of urinary incontinence in
      older Mexican-American women. DESIGN: Cross-sectional analysis of a longitudinal
      survey of a representative sample of older Mexican Americans. SETTING: Five
      southwestern states in the United States. PARTICIPANTS: A total of 1589 Mexican
      American women, aged 65 and older who were part of the Hispanic Established
      Population for the Epidemiologic Study of the Elderly. MEASUREMENTS: Self
      reported psychosocial, demographic, and health variables; self-reported history
      of symptoms of urinary incontinence. RESULTS: Two hundred thirty-nine (15%) of
      the 1589 Mexican-American women reported having urinary incontinence. Almost 33%
      reported urge incontinence symptoms, 10% reported stress incontinence symptoms,
      and 42% had symptoms suggestive of mixed incontinence. Thirty-five percent of
      subjects reported incontinence episodes with moderate to large amounts of urine
      loss, and 15% reported that their urinary symptoms kept them from engaging in
      social activities. Age and body mass index were risk factors for incontinence
      (P=.02 and P=.03, respectively). CONCLUSION: This is the first community-based
      survey examining rates of urinary incontinence in Mexican-American women. The
      prevalence of urinary incontinence may be lower in older Mexican-American women
      than in the general population. They may also have a higher percentage of urge as
      opposed to stress incontinence symptoms and may suffer from moderate to large
      volumes of urine loss associated with their incontinence episodes.

PMID- 14687389
TI  - Quality of life while dying: a qualitative study of terminally ill older men.
AB  - OBJECTIVES: To characterize the experience of quality of life while dying from
      the perspective of terminally ill men. DESIGN: Descriptive study involving
      semistructured interviews. SETTING: Patients attending clinics at two university
      affiliated medical centers were interviewed in a private conference room or in
      their homes. PARTICIPANTS: Twenty-six men identified by their physicians as
      having terminal heart disease or cancer. Eligible participants acknowledged that
      they had serious illness. MEASUREMENTS: The interview contained open-ended
      questions such as: "What are the most important things in your life right now?"
      The interview also contained closed-ended questions about symptom intensity,
      presence of depressed mood, and other items related to overall quality of life.
      The open-ended questions were tape-recorded, transcribed, and analyzed using
      grounded theory methods. The closed-ended questions were analyzed using
      descriptive statistics. RESULTS: Participants believed that death was near.
      Participants saw engaging in hobbies and other enjoyable activities as an
      alternative to moving into the final stage of illness, in which they saw
      themselves as actively dying. They admitted to occasionally ignoring prescribed
      diets; these actions improved their overall quality of life but worsened
      symptoms. New symptoms brought concerns about progression to active dying. They
      anticipated what their dying would be like and how it would affect others.
      Participants believed that their actions in the present could improve the quality
      of their dying and lessen the burden of their deaths on others. Many participants
      therefore were preparing for death by engaging in such tasks as putting their
      finances in order and planning their funerals, to relieve anticipated burden on
      loved ones. CONCLUSION: To help terminally ill patients plan for the end of life,
      clinicians are encouraged to become familiar with their patients' experiences of
      living with terminal illness, to identify each patient's unique priorities, and
      to incorporate that information into care plans aimed at maximizing quality of
      life at the end of life.

PMID- 14687388
TI  - End-of-life care in assisted living and related residential care settings:
      comparison with nursing homes.
AB  - OBJECTIVES: To define the current state of end-of-life care in residential
      care/assisted living (RC/AL) facilities and nursing homes (NHs) and to compare
      these two types of care settings. DESIGN: Interviews of staff and family
      informants about deaths that occurred during a longitudinal study. SETTING: Fifty
      five RC/AL facilities and 26 NHs in Florida, Maryland, New Jersey, and North
      Carolina. PARTICIPANTS: Two hundred twenty-four staff and family informants that
      best knew the 73 RC/AL residents and 72 NH residents who died in or within 3 days
      after discharge from a study facility. MEASUREMENTS: Telephone interviews
      conducted with the facility staff member who knew the decedent best and the
      family member who was most involved in care during the last month of life of the
      decedent. Data were collected on circumstances of death, perceptions of dying
      process, cause of death, care during the last month of life, mood, discomfort,
      and family satisfaction. RESULTS: Most decedents died in the facility where they
      had resided, and more than half of the subjects were alone when they died.
      Greater proportions of staff and family in the NHs knew that the resident's death
      was only days or weeks away. Both RC/AL and NH residents experienced few highly
      negative moods, and even on their most uncomfortable day, the overall discomfort
      was low for residents in both facility types. Summary ratings of family
      satisfaction were significantly higher for the RC/AL (32.1) than the NH (41.2)
      group (P=.016). CONCLUSION: These data suggest that end-of-life care in RC/AL
      settings appears similar in process and outcomes to that provided in NHs. Thus,
      aging and dying-in-place can effectively occur in RC/AL.

PMID- 14687391
TI  - Measuring life-space mobility in community-dwelling older adults.
AB  - OBJECTIVES: To evaluate the validity and reliability of a standardized approach
      for assessing life-space mobility (the University of Alabama at Birmingham Study
      of Aging Life-Space Assessment (LSA)) and its ability to detect changes in life
      space over time in community-dwelling older adults. DESIGN: Prospective,
      observational cohort study. SETTING: Five counties (three rural and two urban) in
      central Alabama. PARTICIPANTS: Community-dwelling Medicare beneficiaries (N=306;
      46% male, 43% African American) who completed in-home baseline interviews and 2
      week and 6-month telephone follow-up interviews. MEASUREMENTS: The LSA assessed
      the range, independence, and frequency of movement over the 4 weeks preceding
      assessments. Correlations between the baseline LSA and measures of physical and
      mental health (physical performance, activities of daily living, instrumental
      activities of daily living, a global measure of health (the short form-12
      question survey), the Geriatric Depression Scale, and comorbidities) established
      validity. Follow-up LSA scores established short-term test-retest reliability and
      the ability of the LSA to detect change. RESULTS: For all LSA scoring methods,
      baseline and 2-week follow-up LSA correlations were greater than 0.86 (95%
      confidence interval=0.82-0.97). Highest correlations with measures of physical
      performance and function were noted for the LSA scoring method considering all
      attributes of mobility. The LSA showed both increases and decreases at 6 months.
      DISCUSSION: Life-space correlated with observed physical performance and self
      reported function. It was stable over a 2-week period yet showed changes at 6
      months.

PMID- 14687390
TI  - Sarcopenia: alternative definitions and associations with lower extremity
      function.
AB  - OBJECTIVES: To compare two sarcopenia definitions and examine the relationship
      between them and lower extremity function and other health related factors using
      data from the baseline examination of the Health Aging and Body Composition
      (Health ABC) Study. DESIGN: Observational cohort study. SETTING: Two U.S.
      communities in Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS:
      Participants were aged 70 to 79 (N=2984, 52% women, 41% black). MEASUREMENTS:
      Participants were assessed using dual energy x-ray absorptiometry and were
      classified as sarcopenic using two different approaches to adjust lean mass for
      body size: appendicular lean mass divided by height-squared (aLM/ht2) and
      appendicular lean mass adjusted for height and body fat mass (residuals).
      RESULTS: These methods differed substantially in the classification of
      individuals as being sarcopenic, especially those who were more obese. The former
      method was highly correlated with body mass index and identified fewer overweight
      or obese individuals as sarcopenic. In both men and women, none of the obese
      group would be considered sarcopenic using the aLM/ht2 method, compared with
      11.5% of men and 21.0% of women using the residuals method. In men, both
      classifications of sarcopenia were associated with smoking, poorer health, lower
      activity, and impaired lower extremity function. Fewer associations with health
      factors were noted in women, but the classification based on both height and fat
      mass was more strongly associated with lower extremity functional limitations
      (odds ratio (OR)=0.9, 95% confidence interval (CI)=0.7-1.2 for low kg/ht2;
      OR=1.9, 95% CI=1.4-2.5 for lean mass adjusted for height and fat mass).
      CONCLUSION: These findings suggest that fat mass should be considered in
      estimating prevalence of sarcopenia in women and in overweight or obese
      individuals.

PMID- 14687392
TI  - Body mass index and hospitalization in the elderly.
AB  - OBJECTIVES: To explore the association between body mass index (BMI) and hospital
      usage in the elderly. DESIGN: Retrospective cohort study. SETTING: Medicare
      Current Beneficiary Survey (1992-94). PARTICIPANTS: Eight thousand seven hundred
      fifty-four noninstitutionalized individuals aged 65 to 100 without cancer at
      baseline and with available data on height and weight. MEASUREMENTS: BMI
      categorized by quintiles and by the 1998 National Heart Lung and Blood Institute
      (NHLBI) BMI classification. Poisson regression was used for multivariate analyses
      relating BMI to number of hospitalizations, adjusting for sex, age, smoking
      status, and heart disease. RESULTS: During 20464 years of observation, 1199
      individuals had 4096 hospitalizations and 34190 hospital days. Individuals in the
      lowest BMI quintile had a higher risk of hospitalization than those in the middle
      BMI quintile (RR=1.22; 95% confidence interval=1.1-1.4); stratified analyses by
      age revealed that this association remained for individuals aged 65 to 75. Using
      the NHLBI classification, underweight, overweight, mild obesity, and moderate to
      severe obesity were related to higher risk of hospitalizations than normal BMI in
      individuals aged 65 to 75. In individuals older than 75, underweight, overweight,
      and mild obesity were not related to a higher risk of hospitalizations. Moderate
      to severe obesity was related to a higher risk of hospitalization in individuals
      aged 75 to 89, which represented only 1.5% of the sample. CONCLUSION: BMI is not
      a predictor of hospitalization for most individuals aged 75 and older.

PMID- 14687393
TI  - Self- and informant report of financial abilities in patients with Alzheimer's
      disease: reliable and valid?
AB  - OBJECTIVES: To evaluate the consistency, stability, and accuracy of reports by
      patients with Alzheimer's disease (AD) and their caregivers regarding the
      patients' premorbid and current financial abilities. DESIGN: Consistency of
      reports was assessed within patient/caregiver dyads and within control/control
      informant dyads. Stability of reports over a 1-month interval was assessed for
      each group: patients with AD, caregivers, controls, and control informants.
      Accuracy of each group's reports was evaluated in reference to patients' and
      controls' performance on a direct psychometric measure of financial capacity.
      SETTING: University medical center. PARTICIPANTS: Twenty patients with AD and 20
      family caregivers; 23 controls and 23 family informants. MEASUREMENTS: The Prior
      Financial Capacity Form (PFCF) and the Current Financial Capacity Form (CFCF)
      were used. Parallel versions assessed self-report (patients, controls) and
      informant report (caregivers, control informants) at two visits 1 month apart.
      Patients with AD and controls were also administered the Financial Capacity
      Instrument (FCI), a direct assessment of the same abilities reported on the PFCF
      and CFCF. RESULTS: Patients with AD reported that they had more-intact current
      abilities than their caregivers reported. Patients with AD and their caregivers
      showed lower levels of stability over time on the PFCF and CFCF than did controls
      and their informants. Half of the patients with AD overestimated their current
      abilities relative to their FCI performance, whereas caregivers demonstrated both
      underestimation and overestimation errors. Controls and informants evidenced high
      levels of consistency, stability, and accuracy in PFCF and CFCF ratings.
      CONCLUSION: Patients with AD overestimate their financial abilities in comparison
      with the reports of their family caregivers. Both patients and caregivers'
      reports of patients' financial abilities showed limited stability and validity.
      The reliability and accuracy of self- and informant reports of financial
      abilities may be compromised in the context of dementia and caregiving,
      underscoring the need for direct assessment methods to augment self- and
      informant report in assessing functional decline in dementia.

PMID- 14687394
TI  - The relationship between androgens and arterial stiffness in older men.
AB  - OBJECTIVES: To assess the relationship between endogenous androgen levels and
      arterial stiffness in older men. DESIGN: A retrospective, cross-sectional study.
      SETTING: A London hospital-based, clinical research unit for the elderly.
      PARTICIPANTS: Fifty-five men (mean age+/-standard deviation=71.1+/-8.0).
      INTERVENTION: Sex hormone-binding globulin (SHBG), testosterone, and
      dehydroepiandrosterone sulfate (DHEAS) were measured in all subjects who had a
      stored serum sample drawn the same day as arterial stiffness measures were
      performed. Free testosterone index (FTI) was calculated ((total
      testosterone/SHBG) x 100 (%)). The measures of arterial stiffness used were pulse
      wave velocity (PWV) using the Complior system and systemic arterial compliance
      (SAC) using the area method. MEASUREMENTS: Relationship between arterial
      stiffness and serum androgens. RESULTS: : FTI showed a strong positive
      relationship with SAC (r=0.507, P<.001) and, correspondingly, an inverse
      relationship with carotid-femoral (C-F) and carotid-radial (C-R) PWV (r=-0.427
      and -0.402, respectively, P<or=.002). With multiple regression, including age,
      blood pressure, cholesterol, body mass index, and waist/hip ratio, FTI remained a
      significant determinant of SAC and C-R PWV but not C-F PWV. In the subgroup of
      men without cardiovascular disease or vasoactive medication use (n=37), all three
      relationships remained significant. DHEAS was inversely related to C-F PWV only
      (r=-0.304, P=.041). CONCLUSION: The known association between lower androgenicity
      and increased cardiovascular risk in men might be explained by altered vascular
      stiffness.

PMID- 14687395
TI  - Influence of executive function on locomotor function: divided attention
      increases gait variability in Alzheimer's disease.
AB  - OBJECTIVES: To evaluate how cognitive function and divided attention affect gait
      in Alzheimer's disease (AD). DESIGN: Cross-sectional intervention study with
      subjects serving as their own controls. SETTING: Inpatient unit and outpatient
      clinic for patients with dementia located at a Veterans Affairs Medical Center.
      PARTICIPANTS: Twenty-eight patients diagnosed with probable AD. INTERVENTION:
      Performance of a cognitive task (repeating random digits) while walking.
      MEASUREMENTS: Neuropsychological measures including clock drawing, verbal
      fluency, and digit span were obtained along with the Clinical Dementia Rating and
      Mini-Mental State Examination, the measures of dementia severity. Gait speed and
      stride-to-stride variability of gait rhythm were measured, once during normal
      walking and once during dual-task walking. RESULTS: During usual walking,
      subjects walked slowly and with greater gait variability than older adults
      without AD. Gait speed was significantly reduced (P<.012) and gait variability
      increased with dual-task walking (P<.007). The effect on gait variability was
      larger than the effect on gait speed (P<.015). Executive and neuropsychological
      function were significantly (P<.02) associated with the increased gait
      variability that occurred when walking with divided attention but not with gait
      speed or usual, single-task walking measures of gait. CONCLUSION: Divided
      attention markedly impairs the ability of patients with AD to regulate the stride
      to-stride variations in gait timing. This susceptibility to distraction and its
      effect on stride time variability, a measure of gait unsteadiness, could
      partially explain the predilection to falling observed in patients with dementia.
      The results also support the concept that persons with AD have significant
      impairments in the cognitive domain of attention and that locomotor function
      relies upon cognitive, especially executive, function.

PMID- 14687396
TI  - Cognitive impairment decreases postural control during dual tasks in geriatric
      patients with a history of severe falls.
AB  - OBJECTIVES: To investigate the influence of dual tasks, cognitive strategies, and
      fear of falling on postural control in geriatric patients with or without
      cognitive impairment and with a history of falls resulting in injury. DESIGN:
      Experimental three-group design. SETTING: Geriatric hospital. PARTICIPANTS:
      Twenty young healthy adults (mean age+/-standard deviation=25.4+/-4.4), 20
      geriatric patients with a history of severe falls without cognitive impairment
      (mean age=82.6+/-5.5, mean Mini-Mental State Examination (MMSE) score=27.8+/-2.0)
      and 20 geriatric patients with a history of severe falls and cognitive impairment
      (mean age=83.2+/-5.5, mean MMSE=19.2+/-3.3). MEASUREMENTS: Motor performance:
      sway area and lateral and anterior-posterior sway angles. Cognition:
      semiautomated calculation steps (serial 2 forward) and nonautomated calculation
      derived from MMSE (serial 7 retro). Motor and cognitive performances were
      examined as single and dual tasks. Strategy decision, fear of falling, and
      subjective perception of motor and cognitive performance were assessed as
      covariates for dual-task performances. RESULTS: Motor performance decreased
      significantly during all dual tasks in geriatric patients with cognitive
      impairment and a history of falls resulting in injury. Cognitive performance was
      different depending on the task and group. Choice of cognitive strategies or fear
      of falling did not influence the dual-task performances. CONCLUSION: Even simple
      additional tasks substantially decrease postural stability due to attention
      related cognitive deficits in cognitively impaired geriatric patients with a
      history of severe falls. The findings may help to explain the increased incidence
      and severity of falls in geriatric patients with cognitive impairment and a
      history of falls resulting in injury.

PMID- 14687397
TI  - Differing risk factors for falls in nursing home and intermediate-care residents
      who can and cannot stand unaided.
AB  - OBJECTIVES: To determine fall risk factors in nursing home and intermediate-care
      residents who can and cannot stand unaided. DESIGN: Prospective cohort study.
      SETTING: Residential elderly care facilities in Sydney, Australia. PARTICIPANTS:
      One thousand people aged 65 to 103 (mean age +/- standard deviation: 85.0 +/-
      7.4). MEASUREMENTS: Accidental falls. RESULTS: Fall rates were highest in those
      with fair standing balance, intermediate in those with the best standing balance,
      and lowest in those with the worst standing balance. This nonlinear pattern was
      even more striking when subjects were categorized according to their standing
      balance and ability to rise from a chair. Using this dual classification, fall
      rates were highest in those who could rise from a chair but could not stand
      unaided (81%) and lowest in those who could neither rise from a chair nor stand
      unaided (48%). In residents who could stand unaided, risk factors included
      increased age, male sex, higher care classifications, incontinence, psychoactive
      medication use, previous falls, and slow reaction times. In contrast, quite
      different risk factors were evident in residents who could not stand unaided,
      with a number of known fall risk factors (previous stroke, reduced ability to
      rise from a chair, slow reaction times) being associated with fewer falls. In
      this group, risk factors were intermediate versus nursing home care, poor health
      status, psychoactive medication use, Parkinson's disease, previous falls, and
      being able to get out of a chair. CONCLUSION: The findings indicate that there
      are different risk factors for falls for people living in residential aged care
      facilities who can and cannot stand unaided. These findings provide important
      information for developing fall-prevention strategies and suggest that those who
      can stand unaided but have multiple falls risk factors constitute the highest
      priority group for such interventions.

PMID- 14687398
TI  - Admission and continued-stay criteria for assisted living facilities.
AB  - As residents in assisted living facilities (ALFs) try to "age in place" but
      decline in health, the facilities, families, and residents must find a balance
      between protecting the health and safety of residents in ALFs and maintaining
      their desire to live independently. The assisted living industry incorporates
      resident autonomy into its goals, but with regard to resident health and safety,
      recent reports have found that ALF staff are struggling to provide adequate care
      for residents with increasingly complex needs. Moreover, state regulations are
      not consistent in obligating ALFs to prioritize adequate health care and
      protection for residents over resident autonomy, or vice versa. A set of
      admission and continued stay criteria for individuals residing in assisted living
      that could serve as a guideline for state regulations in addressing the balance
      between safety and autonomy in ALFs is recommended.

PMID- 14687399
TI  - Blood pressure concordance in older married Mexican-American couples.
AB  - There is a strong link between marital status and health. What has been lacking
      in previous literature is the attention to health similarities or concordance in
      health between married adults, especially in older ethnic couples. To address the
      issue of health concordance, the investigators examined the extent to which blood
      pressure is concordant between older Mexican-American spouses. Using Wave 1 of
      the Hispanic Established Population for the Epidemiological Study of the Elderly
      (n=553 married couples), ordinary least squares and logistic regression were
      conducted to assess the degree of similarity between married adults for systolic
      and diastolic blood pressure (measured as an average and as percent
      hypertensive). Strong associations were found between spouses for both systolic
      and diastolic blood pressure (correlation coefficient=0.32 and 0.34,
      respectively). These associations remain even when spouse age, weight, and health
      characteristics are included in the models. With life expectancy and the time
      spent in marriage increasing, examining the concordance in health between older
      adults becomes increasingly important to target older spouses at risk for
      declines in health.

PMID- 14687400
TI  - Developing a stroke unit using the acute care for elders intervention and model
      of care.
AB  - The Acute Care for Elders (ACE) model of care is a multicomponent intervention
      that improves outcomes for older patients hospitalized for acute medical
      illnesses. Likewise, stroke units improve outcomes for patients with acute
      stroke, yet the descriptions of their structure and approach to stroke management
      are heterogeneous. The purpose of this article is to describe how implementing
      the ACE model of care, using a continuous quality-improvement process, can serve
      as a foundation for a successful stroke unit aimed at improving stroke care. The
      ACE intervention (a prepared environment, interdisciplinary team management,
      patient-centered nursing care plans, early discharge planning, and review of
      medical care) was amplified in a community teaching hospital for stroke-specific
      care by creating a stroke interdisciplinary team, evidence-based stroke orders
      and protocols, and a redesigned environment. Administrative data show that the
      ACE model can be successfully adapted to create a disease-specific program for
      stroke patients, having the potential to improve the process of care and clinical
      stroke outcomes.

PMID- 14687402
TI  - Older adults who reside in long-term care facilities: a high- risk population for
      invasive pneumococcal disease.

PMID- 14687404
TI  - The phenomenon of premonition of death in older patient.

PMID- 14687403
TI  - Biomarkers in subjects with amnestic mild cognitive impairment.

PMID- 14687405
TI  - Postoperative cognitive decline: association with preoperative tumor necrosis
      factor-alpha levels.

PMID- 14687406
TI  - Serum cystatin C may be a better marker of renal impairment than creatinine.

PMID- 14687407
TI  - Osteoarthritis and rheumatoid arthritis: will new data clarify the risk:benefit
      ratio of cyclooxygenase-2 inhibitors?

PMID- 14687408
TI  - Androgen metabolism in females does not occur in male organs.

PMID- 14687409
TI  - The origin of the word geriatrics.

PMID- 14687410
TI  - Atorvastatin, 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, reduces
      bone resorption in the elderly.

PMID- 14687411
TI  - Oral dryness: subjective perception and objective causes.

PMID- 14687413
TI  - Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced
      myocarditis in mice.
AB  - BACKGROUND: Viral replication as well as an immunopathological component are
      assumed to be involved in the development of coxsackie B virus (CBV)-induced
      myocarditis. We observed that mycophenolic acid (MPA), the active metabolite of
      the immunosuppressive agent mycophenolate mofetil (MMF), inhibits coxsackie B3
      virus (CBV3) replication in primary Human myocardial fibroblasts. We therefore
      studied whether MMF, which is thus endowed with a direct antiviral as well as
      immunosuppressive effect, may prevent CBV-induced myocarditis in a murine model.
      RESULTS: Four week old C3H-mice were infected with CBV3 and received twice daily,
      for 7 consecutive days (from one day before to 5 days post-virus inoculation)
      treatment with MMF via oral gavage. Treatment with MMF resulted in a significant
      reduction in the development of CBV-induced myocarditis as assessed by
      morphometric analysis, i.e. 78% reduction when MMF was administered at 300
      mg/kg/day (p < 0.001), 65% reduction at 200 mg/kg/day (p < 0.001), and 52%
      reduction at 100 mg/kg/day (p = 0.001). The beneficial effect could not be
      ascribed to inhibition of viral replication since titers of infectious virus and
      viral RNA in heart tissue were increased in MMF-treated animals as compared to
      untreated animals. CONCLUSION: The immunosuppressive agent MMF results in an
      important reduction of CBV3-induced myocarditis in a murine model.

PMID- 14687414
TI  - The tyranny of adenosine recognition among RNA aptamers to coenzyme A.
AB  - BACKGROUND: Understanding the diversity of interactions between RNA aptamers and
      nucleotide cofactors promises both to facilitate the design of new RNA enzymes
      that utilize these cofactors and to constrain models of RNA World evolution. In
      previous work, we isolated six pools of high affinity RNA aptamers to coenzyme A
      (CoA), the principle cofactor in biological acyltransfer reactions.
      Interpretation of the evolutionary significance of those results was made
      difficult by the fact that the affinity resin attachment strongly influenced the
      outcome of those selections. Here we describe the selection of four new pools
      isolated on a disulfide-linked CoA affinity matrix to minimize context-dependent
      recognition imposed by the attachment to the solid support. RESULTS: The four new
      aptamer libraries show no sequence or structural relation to a previously
      dominant CoA-binding species, even though they were isolated from the same
      initial random libraries. Recognition appears to be limited to the adenosine
      portion of the CoA--in particular the Hoogsteen edge--for most isolates surveyed,
      even when a counter selection was employed to remove such RNAs. Two of the
      recovered isolates are eluted with intact CoA more efficiently than with AMP
      alone suggesting a possible pantotheine interaction. However, a detailed
      examination of recognition specificity revealed that the 3' phosphate of CoA, and
      not the pantotheine arm, determined recognition by these two isolates.
      CONCLUSION: Most aptamers that have been targeted towards cofactors containing
      adenosine recognize only the adenosine portion of the cofactor. They do not
      distinguish substituents on the 5' carbon, even when those substituents have
      offered hydrogen bonding opportunities and the selection conditions discouraged
      adenosine recognition. Beyond hydrogen bonding, additional factors that guide the
      selection towards adenosine recognition include aromatic stacking interactions
      and relatively few rotational degrees of freedom. In the present work, a
      sterically accessible, disulfide-linked CoA affinity resin afforded the selection
      of a more diverse aptamer collection then previous work with a N6 linked CoA
      resin.

PMID- 14687416
TI  - Hepatolithiasis with biliary ascariasis--a case report.
AB  - BACKGROUND: Biliary ascariasis is regarded as possible etiological factor for
      hepatolithiasis. Here we report one case of a patient with hepatolithiasis with
      biliary ascariasis who developed a liver abscess, which was treated with partial
      hepatectomy. CASE PRESENTATION: A young adult female presented with epigastric
      pain and vomiting with repeated attacks of cholangitis. ERCP showed evidence of
      multiple intrahepatic calculi with the development of abscess in the left lobe of
      liver. The patient underwent partial hepatectomy and was found to have biliary
      ascariasis on histology. She was treated with antihelmenthic therapy and has had
      an uneventful postoperative period of 2 years. CONCLUSION: Biliary ascariasis
      with hepatolithiasis, although rare, should be considered in endemic countries.

PMID- 14687415
TI  - The PAM domain, a multi-protein complex-associated module with an all-alpha-helix
      fold.
AB  - BACKGROUND: Multimeric protein complexes have a role in many cellular pathways
      and are highly interconnected with various other proteins. The characterization
      of their domain composition and organization provides useful information on the
      specific role of each region of their sequence. RESULTS: We identified a new
      module, the PAM domain (PCI/PINT associated module), present in single subunits
      of well characterized multiprotein complexes, like the regulatory lid of the 26S
      proteasome, the COP-9 signalosome and the Sac3-Thp1 complex. This module is an
      around 200 residue long domain with a predicted TPR-like all-alpha-helical fold.
      CONCLUSIONS: The occurrence of the PAM domain in specific subunits of multimeric
      protein complexes, together with the role of other all-alpha-helical folds in
      protein-protein interactions, suggest a function for this domain in mediating
      transient binding to diverse target proteins.

PMID- 14687417
TI  - Sub-cellular trafficking of phytochemicals explored using auto-fluorescent
      compounds in maize cells.
AB  - BACKGROUND: Little is known regarding the trafficking mechanisms of small
      molecules within plant cells. It remains to be established whether phytochemicals
      are transported by pathways similar to those used by proteins, or whether the
      expansion of metabolic pathways in plants was associated with the evolution of
      novel trafficking pathways. In this paper, we exploited the induction of green
      and yellow auto-fluorescent compounds in maize cultured cells by the P1
      transcription factor to investigate their targeting to the cell wall and vacuole,
      respectively. RESULTS: We investigated the accumulation and sub-cellular
      localization of the green and yellow auto-fluorescent compounds in maize BMS
      cells expressing the P1 transcription factor from an estradiol inducible
      promoter. We established that the yellow fluorescent compounds accumulate inside
      the vacuole in YFBs that resemble AVIs. The green fluorescent compounds
      accumulate initially in the cytoplasm in large spherical GFBs. Cells accumulating
      GFBs also contain electron-dense structures that accumulate initially in the ER
      and which later appear to fuse with the plasma membrane. Structures resembling
      the GFBs were also observed in the periplasmic space of plasmolized cells.
      Ultimately, the green fluorescence accumulates in the cell wall, in a process
      that is insensitive to the Golgi-disturbing agents BFA and monensin. CONCLUSIONS:
      Our results suggest the presence of at least two distinct trafficking pathways,
      one to the cell wall and the other to the vacuole, for different auto-fluorescent
      compounds induced by the same transcription factor in maize BMS cells. These
      compartments represent two of the major sites of accumulation of phenolic
      compounds characteristic of maize cells. The secretion of the green auto
      fluorescent compounds occurs by a pathway that does not involve the TGN,
      suggesting that it is different from the secretion of most proteins,
      polysaccharides or epicuticular waxes. The yellow auto-fluorescent compounds
      accumulate in a vacuolar compartment, in structures that resemble the AVIs
      present in many cells accumulating anthocyanins. Together, our studies suggest
      that the accumulation of auto-fluorescent compounds can provide a powerful tool
      to dissect the trafficking of phytochemicals, knowledge necessary for the
      efficient engineering of plant metabolism.

PMID- 14687419
TI  - Reconsidering the use of rankings in the valuation of health states: a model for
      estimating cardinal values from ordinal data.
AB  - BACKGROUND: In survey studies on health-state valuations, ordinal ranking
      exercises often are used as precursors to other elicitation methods such as the
      time trade-off (TTO) or standard gamble, but the ranking data have not been used
      in deriving cardinal valuations. This study reconsiders the role of ordinal ranks
      in valuing health and introduces a new approach to estimate interval-scaled
      valuations based on aggregate ranking data. METHODS: Analyses were undertaken on
      data from a previously published general population survey study in the United
      Kingdom that included rankings and TTO values for hypothetical states described
      using the EQ-5D classification system. The EQ-5D includes five domains (mobility,
      self-care, usual activities, pain/discomfort and anxiety/depression) with three
      possible levels on each. Rank data were analysed using a random utility model,
      operationalized through conditional logit regression. In the statistical model,
      probabilities of observed rankings were related to the latent utilities of
      different health states, modeled as a linear function of EQ-5D domain scores, as
      in previously reported EQ-5D valuation functions. Predicted valuations based on
      the conditional logit model were compared to observed TTO values for the 42
      states in the study and to predictions based on a model estimated directly from
      the TTO values. Models were evaluated using the intraclass correlation
      coefficient (ICC) between predictions and mean observations, and the root mean
      squared error of predictions at the individual level. RESULTS: Agreement between
      predicted valuations from the rank model and observed TTO values was very high,
      with an ICC of 0.97, only marginally lower than for predictions based on the
      model estimated directly from TTO values (ICC = 0.99). Individual-level errors
      were also comparable in the two models, with root mean squared errors of 0.503
      and 0.496 for the rank-based and TTO-based predictions, respectively.
      CONCLUSIONS: Modeling health-state valuations based on ordinal ranks can provide
      results that are similar to those obtained from more widely analyzed valuation
      techniques such as the TTO. The information content in aggregate ranking data is
      not currently exploited to full advantage. The possibility of estimating cardinal
      valuations from ordinal ranks could also simplify future data collection
      dramatically and facilitate wider empirical study of health-state valuations in
      diverse settings and population groups.

PMID- 14687418
TI  - Protection against acute adriamycin-induced cardiotoxicity by garlic: role of
      endogenous antioxidants and inhibition of TNF-alpha expression.
AB  - BACKGROUND: Oxidative stress is the major etiopathological factor in adriamycin
      induced cardiotoxicity. Relatively low amounts of endogenous antioxidant makes
      the heart vulnerable to oxidative stress-induced damage. Chronic oral
      administration of garlic has been reported to enhance the endogenous antioxidants
      of heart. We hypothesized that garlic-induced enhanced cardiac antioxidants may
      offer protection against acute adriamycin-induced cardiotoxicity. RESULTS: Rats
      were either administered freshly prepared garlic homogenate (250 and 500 mg/kg
      daily, orally, for 30 days) or probucol (cumulative dose, 120 mg/kg body weight
      divided in 12, i.p. over a period of 30 days) or double distilled water
      (vehicle), followed by a single dose of adriamycin (30 mg/kg i.p.). In the
      adriamycin group, increased oxidative stress was evidenced by a significant
      increase in myocardial TBARS (thiobarbituric acid reactive substances) and
      decrease in myocardial SOD (superoxide dismutase), catalase and GPx (glutathione
      peroxidase) activity. Histopathological studies showed focal as well as
      subendocardial myocytolysis with infiltration of macrophages, lymphocytes and
      edema. Immunocytochemistry showed marked expression of TNF-alpha (tumor necrosis
      factor-alpha) in the myocardium. Increase in myocardial TBARS and decrease in
      endogenous antioxidants by adriamycin was prevented significantly in the garlic
      treated rat hearts, which was comparable to the probucol-treated group.
      Histopathological evidence of protection was also evident in both garlic-treated
      and probucol-treated groups. Probucol, 250 mg/kg and 500 mg/kg of garlic reduced
      adriamycin induced TNF-alpha expression in the myocardium and was associated with
      reduced myocyte injury. CONCLUSIONS: It is concluded that chronic garlic
      administration prevents acute adriamycin-induced cardiotoxicity and decreases
      myocardial TNF-alpha expression.

PMID- 14687420
TI  - Generalized cost-effectiveness analysis for national-level priority-setting in
      the health sector.
AB  - Cost-effectiveness analysis (CEA) is potentially an important aid to public
      health decision-making but, with some notable exceptions, its use and impact at
      the level of individual countries is limited. A number of potential reasons may
      account for this, among them technical shortcomings associated with the
      generation of current economic evidence, political expediency, social preferences
      and systemic barriers to implementation. As a form of sectoral CEA, Generalized
      CEA sets out to overcome a number of these barriers to the appropriate use of
      cost-effectiveness information at the regional and country level. Its application
      via WHO-CHOICE provides a new economic evidence base, as well as underlying
      methodological developments, concerning the cost-effectiveness of a range of
      health interventions for leading causes of, and risk factors for, disease.The
      estimated sub-regional costs and effects of different interventions provided by
      WHO-CHOICE can readily be tailored to the specific context of individual
      countries, for example by adjustment to the quantity and unit prices of
      intervention inputs (costs) or the coverage, efficacy and adherence rates of
      interventions (effectiveness). The potential usefulness of this information for
      health policy and planning is in assessing if current intervention strategies
      represent an efficient use of scarce resources, and which of the potential
      additional interventions that are not yet implemented, or not implemented fully,
      should be given priority on the grounds of cost-effectiveness.Health policy
      makers and programme managers can use results from WHO-CHOICE as a valuable input
      into the planning and prioritization of services at national level, as well as a
      starting point for additional analyses of the trade-off between the efficiency of
      interventions in producing health and their impact on other key outcomes such as
      reducing inequalities and improving the health of the poor.

PMID- 14687421
TI  - Problems and solutions in calculating quality-adjusted life years (QALYs).
AB  - The quality-adjusted life-year (QALY) is a measure of the value of health
      outcomes. Since health is a function of length of life and quality of life, the
      QALY was developed as an attempt to combine the value of these attributes into a
      single index number. The QALY calculation is simple: the change in utility value
      induced by the treatment is multiplied by the duration of the treatment effect to
      provide the number of QALYs gained. QALYs can then be incorporated with medical
      costs to arrive at a final common denominator of cost/QALY. This parameter can be
      used to compare the cost-effectiveness of any treatment. Nevertheless, QALYs have
      been criticised on technical and ethical grounds. A salient problem relies on the
      numerical nature of its constituent parts. The appropriateness of the QALY
      arithmetical operation is compromised by the essence of the utility scale: while
      life-years are expressed in a ratio scale with a true zero, the utility is an
      interval scale where 0 is an arbitrary value for death. In order to be able to
      obtain coherent results, both scales would have to be expressed in the same units
      of measurement. The different nature of these two factors jeopardises the meaning
      and interpretation of QALYs. A simple general linear transformation of the
      utility scale suffices to demonstrate that the results of the multiplication are
      not invariant. Mathematically, the solution to these limitations happens through
      an alternative calculation of QALYs by means of operations with complex numbers
      rooted in the well known Pythagorean theorem. Through a series of examples, the
      new calculation arithmetic is introduced and discussed.

PMID- 14687422
TI  - Tissue Doppler imaging of carotid plaque wall motion: a pilot study.
AB  - BACKGROUND: Studies suggest the physical and mechanical properties of vessel
      walls and plaque may be of clinical value in the diagnosis and treatment of
      cardiovascular atherosclerotic disease. The purpose of this pilot study was to
      investigate the potential clinical application of ultrasound Tissue Doppler
      Imaging (TDI) of Arterial Wall Motion (AWM) and to quantify simple wall motion
      indices in normal and diseased carotid arteries. METHODS: 224 normal and diseased
      carotid arteries (0-100% stenoses) were imaged in 126 patients (age 25-88 years,
      mean 68 +/- 11). Longitudinal sections of the carotid bifurcation were imaged
      using a Philips HDI5000 scanner and L12-5 probe under optimized TDI settings.
      Temporal and spatial AWMs were analyzed to evaluate the vessel wall displacements
      and spatial gradients at peak systole averaged over 5 cardiac cycles. RESULTS:
      AWM data were successfully extracted in 91% of cases. Within the carotid
      bifurcation/plaque region, the maximum wall dilation at peak systole ranged from 
      100 to 750 microns, mean 335 +/- 138 microns. Maximum wall dilation spatial
      gradients ranged 0-0.49, mean 0.14 +/- 0.08. The AWM parameters showed a wide
      variation and had poor correlation with stenoses severity. Case studies
      illustrated a variety of pertinent qualitative and quantitative wall motion
      features related to the biophysics of arterial disease. CONCLUSION: Our clinical
      experience, using a challenging but realistic imaging protocol, suggests the use
      of simple quantitative AWM measures may have limitations due to high variability.
      Despite this, pertinent features of AWM in normal and diseased arteries
      demonstrate the potential clinical benefit of the biomechanical information
      provided by TDI.

PMID- 14687423
TI  - Regulation of oxygen transport during brain activation: stimulus-induced
      hemodynamic responses in human and animal cortices.
AB  - BACKGROUND: The correlation between regional changes in neuronal activity and
      changes in hemodynamics is a major issue for noninvasive neuroimaging techniques
      such as functional magnetic resonance imaging (fMRI) and near-infrared optical
      imaging (NIOI). A tight coupling of these changes has been assumed to elucidate
      brain function from data obtained with those techniques. In the present study, we
      investigated the relationship between neuronal activity and hemodynamic responses
      in the occipital cortex of humans during visual stimulation and in the
      somatosensory cortex of rats during peripheral nerve stimulation. METHODS: The
      temporal frequency dependence of macroscopic hemodynamic responses on visual
      stimuli was investigated in the occipital cortex of humans by simultaneous
      measurements made using fMRI and NIOI. The stimulus-intensity dependence of both
      microscopic hemodynamic changes and changes in neuronal activity in response to
      peripheral nerve stimulation was investigated in animal models by analyzing
      membrane potential (fluorescence), hemodynamic parameters (visible spectra and
      laser-Doppler flowmetry), and vessel diameter (image analyzer). RESULTS: Above a
      certain level of stimulus-intensity, increases in regional cerebral blood flow
      (rCBF) were accompanied by a decrease in regional cerebral blood volume (rCBV),
      i.e., dissociation of rCBF and rCBV responses occurred in both the human and
      animal experiments. Furthermore, the animal experiments revealed that the
      distribution of increased rCBF and O2 spread well beyond the area of neuronal
      activation, and that the increases showed saturation in the activated area.
      CONCLUSIONS: These results suggest that above a certain level of neuronal
      activity, a regulatory mechanism between regional cerebral blood flow (rCBF) and
      rCBV acts to prevent excess O2 inflow into the focally activated area.

PMID- 14687424
TI  - Power evaluation of disease clustering tests.
AB  - BACKGROUND: Many different test statistics have been proposed to test for spatial
      clustering. Some of these statistics have been widely used in various
      applications. In this paper, we use an existing collection of 1,220,000 simulated
      benchmark data, generated under 51 different clustering models, to compare the
      statistical power of several disease clustering tests. These tests are Besag
      Newell's R, Cuzick-Edwards' k-Nearest Neighbors (k-NN), the spatial scan
      statistic, Tango's Maximized Excess Events Test (MEET), Swartz' entropy test,
      Whittemore's test, Moran's I and a modification of Moran's I. RESULTS: Except for
      Moran's I and Whittemore's test, all other tests have good power for detecting
      some kind of clustering. The spatial scan statistic is good at detecting
      localized clusters. Tango's MEET is good at detecting global clustering. With
      appropriate choice of parameter, Besag-Newell's R and Cuzick-Edwards' k-NN also
      perform well. CONCLUSION: The power varies greatly for different test statistics
      and alternative clustering models. Consideration of the power is important before
      we decide which test statistic to use.

PMID- 14687425
TI  - Positional error in automated geocoding of residential addresses.
AB  - BACKGROUND: Public health applications using geographic information system (GIS)
      technology are steadily increasing. Many of these rely on the ability to locate
      where people live with respect to areas of exposure from environmental
      contaminants. Automated geocoding is a method used to assign geographic
      coordinates to an individual based on their street address. This method often
      relies on street centerline files as a geographic reference. Such a process
      introduces positional error in the geocoded point. Our study evaluated the
      positional error caused during automated geocoding of residential addresses and
      how this error varies between population densities. We also evaluated an
      alternative method of geocoding using residential property parcel data. RESULTS:
      Positional error was determined for 3,000 residential addresses using the
      distance between each geocoded point and its true location as determined with
      aerial imagery. Error was found to increase as population density decreased. In
      rural areas of an upstate New York study area, 95 percent of the addresses
      geocoded to within 2,872 m of their true location. Suburban areas revealed less
      error where 95 percent of the addresses geocoded to within 421 m. Urban areas
      demonstrated the least error where 95 percent of the addresses geocoded to within
      152 m of their true location. As an alternative to using street centerline files
      for geocoding, we used residential property parcel points to locate the
      addresses. In the rural areas, 95 percent of the parcel points were within 195 m
      of the true location. In suburban areas, this distance was 39 m while in urban
      areas 95 percent of the parcel points were within 21 m of the true location.
      CONCLUSION: Researchers need to determine if the level of error caused by a
      chosen method of geocoding may affect the results of their project. As an
      alternative method, property data can be used for geocoding addresses if the
      error caused by traditional methods is found to be unacceptable.

PMID- 14687427
TI  - Overview of the community care network demonstration program and its evaluation.
AB  - This article provides an overview of the evaluation of the National Community
      Care Network Demonstration Program,which began with 25 public-private
      partnerships selected from a diverse range of communities across the United
      States to address problems of lack of insurance, limited access to health care,
      and the health status of their most disadvantaged residents. The 25 public
      private partnerships included an array of individual organizations representing
      health care providers, public health and human service agencies, local
      governments,community-based organizations, and religious and educational
      institutions. The specific findings of the evaluation are the focus of the
      articles in this issue. This overview article supplies the underpinnings of the
      evaluation, including the conceptual framework, methodological challenges, and a
      brief discussion of each of the papers and how they are linked.

PMID- 14687426
TI  - Can surveying practitioners about their practices help identify priority clinical
      practice guideline topics?
AB  - BACKGROUND: Clinical practice guidelines are systematically developed statements
      designed to assist in patient and physician clinical decision making for specific
      clinical circumstances. In order to establish which guideline topics are
      priorities, practitioners were surveyed regarding their current practice.
      METHODS: One hundred ninety-seven practitioners in Ontario, Canada were mailed a
      survey exploring their current practice or opinion regarding the prophylactic use
      of anticonvulsant drugs in patients with malignant glioma who had never had a
      seizure. The survey consisted of seven questions regarding the relevance of a
      guideline on the subject to the practitioner's practice, the proportion of
      clinical cases involving anticonvulsant use, knowledge of existing guidelines on
      this topic, interest in reviewing a completed practice guideline and three
      clinical scenarios. RESULTS: There were 122 respondents who returned the survey
      (62% rate of return). Eighty percent of the practitioners who responded indicated
      that less than 25% of their clinical cases involved the use of anticonvulsants;
      however, only 16% of respondents indicated that a practice guideline would be
      irrelevant to their practice. Eighty percent of respondents volunteered to review
      a draft version of a practice guideline on the use of anticonvulsants. The survey
      presented the practitioners with three scenarios where anticonvulsants in
      patients with brain tumours may be appropriate: peri-operatively in patients
      without seizures, postoperatively in patients currently using anticonvulsants,
      and thirdly in patients not currently using anticonvulsants or undergoing
      surgery. In contrast to the third situation, the first two situations yielded
      considerable variation in practitioner response. CONCLUSION: The survey
      established that there is some variation present in the current practice of
      anticonvulsant use in the patients with brain tumours. Whether there is an
      optimal treatment practice has yet to be determined. Practitioners do seem to
      feel that a guideline on anticonvulsant use in warranted, and most practitioners
      would be interested in being part of the guideline development process.

PMID- 14687428
TI  - Using theories of action to guide national program evaluation and local strategy
      in the community care network demonstration.
AB  - Evaluations of multisite community-based projects are notoriously difficult to
      conceptualize and conduct. Projects may share an overarching vision but operate
      in varying contexts and pursue different initiatives. One tool that can assist
      evaluators facing these challenges is to develop a "theory of action" (TOA) that
      identifies critical assumptions regarding how a program expects to achieve its
      goals. Community Care Network (CCN) evaluators used the TOA to refine research
      questions, define key variables, relate questions to each other, and identify
      when we might realistically expect to observe answers. In this article, the
      authors present their national-level CCN TOA. They also worked with sites to help
      them "surface" their local TOA; the article analyzes the results to determine the
      content, clarity, extent of evidence base, and strategic orientation of theories
      articulated by different sites.

PMID- 14687429
TI  - Members' perceptions of community care network partnerships' effectiveness.
AB  - Investment in voluntary partnerships raises important questions: Should we invest
      in collaboration in moving toward the goals of health system redesign? What makes
      collaborative groups effective? Given the voluntary nature of these partnerships,
      membership perceptions of their experiences and the partnership's effectiveness
      should be important predictors of success. This article provides a preliminary
      analyses of perceived effectiveness of participants' perceptions of their own
      partnership, particularly focusing on leadership, conflict management, decision
      making dynamics, and the breadth and depth of partnership membership. Members'
      perceptions that the partnership membership was "sufficiently broad to accomplish
      objectives" had a negative and highly significant relationship to perceived
      effectiveness. Members' perceptions about leadership being ethical was positively
      related to perceived effectiveness while perceptions that the leadership was not
      effective a keeping the group focused was negatively related to perceived
      effectiveness.

PMID- 14687430
TI  - Collaborative initiatives: where the rubber meets the road in community
      partnerships.
AB  - Amajor challenge facing a community partnership is the implementation of its
      collaborative initiatives. This article examines the progress Community Care
      Networks (CCNs) made in implementing their initiatives and factors that helped or
      hindered their progress. Study findings suggest that partnership progress is
      affected by external market and regulatory factors beyond the control of the
      partnership, the availability of local community resources to support efforts,
      the scope and intensity of tasks associated with an initiative, expansion of the
      partnership to include new members, and the balance of work between partners and
      paid partnership staff. Implications of study findings for community partnerships
      include (1) recognizing and anticipating dependency on others, (2) acknowledging
      that the tasks that lie ahead will be more complicated than imagined, (3)
      maintaining focus on priorities, and (4) learning to be adaptive and creative,
      given a constantly changing environment.

PMID- 14687431
TI  - Community care networks: linking vision to outcomes for community health
      improvement.
AB  - This article examines the relationship between progress toward the Community Care
      Network (CCN) vision and "intermediate outcomes" of 25 community-based health
      partnerships (CCNs). Specific components of the CCN vision were community
      accountability, community health focus, creation of a seamless service continuum,
      and managing under limited resources. Four community outcome dimensions were
      evaluated: access, cost, health, and quality of service delivery integration.
      Overall progress toward the CCN vision was significantly positively related to
      average intermediate outcome score and most highly correlated with two
      dimensions: access and quality of service integration. Qualitative analysis
      suggests that CCN sites accomplished the most along two dimensions--access and
      health--noting that intermediate health outcomes generally were in health
      assessment and information rather than actual health status improvement. Keys to
      outcome achievement appear to be (1) clearly focused intervention; (2) explicit,
      ongoing outcome measurement; and (3) strong integration of separate intervention
      components.

PMID- 14687432
TI  - Sustainability of collaborative capacity in community health partnerships.
AB  - Sustainability is a key requirement for partnership success and a major challenge
      for such organizations. Despite the critical importance of sustainability to the
      success of community health partnerships and the many threats to sustainability,
      there is little evidence that would provide partnerships with clear guidance on
      long-term viability. This article attempts to (1) develop a conceptual model of
      sustainability in community health partnerships and (2) identify potential
      determinants of sustainability using comparative qualitative data from four
      partnerships from the Community Care Network (CCN) Demonstration Program. Based
      on a grounded theory examination of qualitative data from the CCN evaluation, the
      authors hypothesize that there are five primary attributes/ activities of
      partnerships leading to consequential value and eventually to sustainability of
      collaborative capacity. They include outcomes-based advocacy, vision-focus
      balance, systems orientation, infrastructure development, and community linkages.
      The context in which the partnership operates provides the conditions for
      determining the appropriateness and relative impact of each of the factors
      related to creating consequential value in the partnership.

PMID- 14687433
TI  - What have we learned about community partnerships?

PMID- 14687436
TI  - Clinical effect of combination therapy of pioglitazone and an alpha-glucosidase
      inhibitor.
AB  - This study evaluated the efficacy of adding pioglitazone 30 mg to the therapy of
      patients with type 2 diabetes mellitus whose glycaemic control was poor on an
      alpha-glucosidase inhibitor (alpha-GI) alone or in combination with a
      sulphonylurea (SU). The patients (n = 20) had a HbA(1c) level between 7.0 and
      12.0% and the fasting plasma glucose was 7.8 mmol/l or higher. They were treated
      with 30 mg pioglitazone once daily for 16 weeks. The decrease in HbA(1c) at week
      16 of treatment was 0.8% (7.8% at baseline dropping to 7.1% at week 16; p < or =
      0.01). An increase in leptin was observed 4 weeks after starting the post-study
      period (p < or = 0.05). Tumour necrosis factor-alpha (TNF-alpha) and body fat
      percentage did not show any significant alterations. Correlations between the
      decrease in HbA1c at week 16 and characteristic variables of patients were
      examined. A correlation with leptin (p = -0.5632, p < or = 0.05) levels was
      found. Five patients experienced adverse drug reactions, such as oedema,
      hypoglycaemia and increased creatine phosphokinase (CK), all of which were mild
      in severity. The addition of pioglitazone in diabetics whose glycaemic control
      was poor on a alpha-GI alone or with a alpha-GI and SU combination resulted in a
      significant decrease in HbA1c, and the treatment was well-tolerated. Our findings
      also suggest that leptin levels could be useful for assessing responders to
      pioglitazone.

PMID- 14687437
TI  - Focus on anastrozole and breast cancer.
AB  - This commentary article provides an overview of recent clinical research trials
      involving anastrozole and its evolving role in the management of breast cancer.
      Anti-aromatase agents inhibit the cytochrome P-450 component of the aromatase
      enzyme complex responsible for the final step of estrogen biosynthesis in
      peripheral tissues which are the main source of estrogen in postmenopausal women.
      Anastrozole is a third-generation non-steroidal aromatase inhibitor. It has been
      shown to be superior to megestrol acetate, in terms of survival and adverse
      effects, as a second-line therapy in postmenopausal women with estrogen receptor
      (ER)- and/or progesterone receptor (PgR)-positive advanced breast cancer. Phase
      III clinical trials have also demonstrated that anastrozole significantly
      prolongs the time to tumour progression compared with tamoxifen as a first-line
      therapy for ER- and/or PgR-positive advanced breast cancer in postmenopausal
      women. Furthermore, the preliminary results of the Arimidex, Tamoxifen, Alone and
      in Combination (ATAC) study have shown that adjuvant anastrozole is superior to
      tamoxifen in terms of disease-free survival (DFS), non-musculoskeletal adverse
      effects and prevention of contralateral breast cancer in postmenopausal women
      with early, ER-positive breast cancer. Although longer follow-up is required to
      assess the long-term effects of anastrozole on bone mineral density, cognitive
      function and overall survival, the drug has been recently approved for adjuvant
      use in postmenopausal women with early, ER-positive breast cancer who are unable
      to tolerate tamoxifen or at an increased risk of developing thromboembolism or
      endometrial cancer. The potential role of anastrozole in the neoadjuvant setting,
      the management of DCIS, premenopausal breast cancer and breast cancer prevention
      is currently being investigated.

PMID- 14687438
TI  - Comparison of the efficacy of rosuvastatin versus atorvastatin, simvastatin, and
      pravastatin in achieving lipid goals: results from the STELLAR trial.
AB  - In the Statin Therapies for Elevated Lipid Levels compared Across doses to
      Rosuvastatin (STELLAR) trial, the efficacy of rosuvastatin calcium (Crestor) was
      compared with that of atorvastatin (Lipitor), simvastatin (Zocor), and
      pravastatin (Pravachol) for lowering plasma low-density lipoprotein cholesterol
      (LDL-C) after 6 weeks of treatment. In this multicenter, parallel-group, open
      label trial, adults with hypercholesterolemia were randomized to treatments with
      rosuvastatin 10, 20, 40, or 80 mg, atorvastatin 10, 20, 40, or 80 mg, simvastatin
      10, 20, 40, or 80 mg, or pravastatin 10, 20, or 40 mg. Efficacy and safety
      results from this trial have been previously published. The additional analyses
      included in this report show that 53% (83/156) to 80% (125/157) of patients in
      the rosuvastatin 10- to 40-mg groups achieved LDL-C levels < 100 mg/dl (< 2.6
      mmol/l), compared with 18% (28/158) to 70% (115/165) of patients who received
      atorvastatin, 8% (13/165) to 53% (86/163) of patients who received simvastatin,
      and 1% (1/160) to 8% (13/161) of patients who received pravastatin. Other
      additional analyses showed that more patients in the rosuvastatin 10- to 40-mg
      groups than in the comparator groups who were at high risk of coronary heart
      disease according to National Cholesterol Education Program Adult Treatment Panel
      (ATP) III, Joint European Societies, or Canadian guidelines achieved the LDL-C
      goals of < 100 mg/dl (< 2.6 mmol/l) (55% to 77% compared with 0 to 64%), < 3.0
      mmol/l (< 116 mg/dl) (76% to 94% compared with 6% to 81%), and < 2.5 mmol/l (< 97
      mg/dl) (47% to 69% compared with 0 to 53%), respectively. Results favoring
      rosuvastatin versus the comparators were also reported for patients: (a) who had
      triglycerides > or = 200mg/dl (> or = 2.3 mmol/l), and achieved both ATP III LDL
      C and non-high-density lipoprotein cholesterol (non-HDL-C) goals (80% to 84%
      versus 15% to 84%); (b) overall who achieved the Canadian LDL-C goals of < 2.5 (<
      97 mg/dl) to < 5.0 mmol/l (< 193 mg/dl) (85% to 91% versus 44% to 86%); and (c)
      who achieved all 3 Canadian goals for LDL-C, triglycerides (< 3.0 mmol/l [< 266
      mg/dl] to < 2.0 mmol/l [< 177 mg/dl]), and the total cholesterol/high-density
      lipoproteincholesterol ratio (< 4 to < 7) (70% to 83% versus 35% to 79%).

PMID- 14687439
TI  - Medical treatment of miscarriage in a district general hospital is safe and
      effective up to 12 weeks' gestation.
AB  - The findings are reported of a retrospective study of 207 women undergoing
      medical evacuation of the uterus for first trimester miscarriage, using
      mifepristone followed by a single dose of oral misoprostol. All women had the
      diagnosis confirmed by ultrasonography. Complete medical evacuation was achieved
      in 88% of cases. The success rate and incidence of complications was observed to
      be the same regardless of whether gestation was below or above 9 weeks. The
      number of cases in which antibiotic treatment for presumed pelvic infection was
      prescribed was 3%. The incidence of anaemia requiring blood transfusion was 3%.

PMID- 14687440
TI  - Chronic pain management--can we do better? An interview-based survey in primary
      care.
AB  - BACKGROUND: Persisting pain is demoralising and debilitating for patients and
      their carers. Most patients with chronic pain do not need the services of a
      specialised pain clinic and are appropriately managed by their general
      practitioner (GP). METHOD: Interviewers approached 569 GPs to assess their
      satisfaction with the management of patients with chronic non-malignant (i.e. non
      cancer related) pain (CNMP). The survey was carried out from November 2001 to
      January 2002 in general practices in the UK. GPs were randomly selected as
      representative of the basic population who treat CNMP. The survey was conducted
      in a face-to-face interview in the GP surgery using a questionnaire consisting of
      35 open questions covering practice information, treatment of CNMP, pain
      management and multidisciplinary support. RESULTS: 504 (88.6%) of GPs completed
      the structured questionnaire. 81% of GPs believed that a significant number of
      patients received suboptimal management. Optimal control of symptoms was
      estimated to occur in less than half of patients. The main barriers to achieving
      good pain control were identified as side-effects of therapies (74%) and patient
      compliance (58%). 60% of respondents expressed concerns regarding efficacy of
      available therapies. Although 91% of GPs considered specialised pain services as
      beneficial, only 14% of patients were referred to hospital for symptom
      management. 96% of GPs felt that the management of chronic pain could be improved
      in their locality and 81% expressed an interest in relevant training. CONCLUSION:
      Most GPs believe that the management of chronic pain can be improved. Further
      education of all healthcare professionals who manage patients in pain is needed
      to bring about such a change.

PMID- 14687441
TI  - Strategies for continued successful treatment of Alzheimer's disease: switching
      cholinesterase inhibitors.
AB  - Cholinesterase (ChE) inhibitors represent the standard therapeutic approach to
      the treatment of Alzheimer's disease (AD). However, a proportion of patients
      experience lack or loss of therapeutic benefit with an initial agent, or
      discontinue due to safety/tolerability issues. In many instances, no alternative
      treatment is offered once the initial agent has been stopped. Thus, for many
      patients, the total duration of treatment is relatively short in comparison with
      the chronic nature of AD. Switching medications is a common therapeutic strategy
      within many drug classes across many clinical areas following a lack/loss of
      efficacy or safety/tolerability problems, and is also an increasingly important
      concept in the management of AD with ChE inhibitors. A number of open-label
      studies, where patients were switched from donepezil to rivastigmine, have
      indicated that approximately 50% of patients experiencing a lack/loss of efficacy
      with donepezil (a selective acetylcholinesterase [AChE] inhibitor) respond to
      subsequent treatment with rivastigmine (a dual AChE and butyrylcholinesterase
      inhibitor). In these studies, rivastigmine was well tolerated, and the occurrence
      of safety/tolerability problems with donepezil was not predictive of similar
      problems with rivastigmine. In the summer of 2002, leading neurologists and
      psychiatrists attended a medical experts meeting to discuss the clinical
      importance of switching ChE inhibitors in AD. The expert panel examined available
      clinical data, shared clinical experiences, and discussed current clinical
      guidelines for switching. The panel also aimed to reach consensus on 'whom to
      switch', 'when to switch' and 'how to switch'. The key findings from that meeting
      are reported in this review.

PMID- 14687442
TI  - No donepezil discontinuation effect in patients with Alzheimer's disease who were
      switched to rivastigmine after failing to benefit from donepezil treatment.

PMID- 14687443
TI  - Issues to consider when attempting to achieve the American Diabetes Association
      clinical quality requirement for haemoglobin A1c.
AB  - Diabetes mellitus is a chronic disease that is monitored by measurement of
      haemoglobin A1c (A1C) as an index of glycaemic control. The limitations of using
      A1C, given the consensus clinical practice recommendations made by the American
      Diabetes Association, need to be better understood by clinicians. These include
      bias between DCCT-aligned methods, analytical variation and intra-individual
      variation. As intra-individual variation is the principal factor determining
      variation in A1C in rolling means of the last four A1C results and to stable
      patients, clinicians may need to monitor A1C more frequently to achieve precise
      results. Laboratories need to report current values and the analyse six internal
      quality control specimens for each analytical run. 'Delta check' criteria ought
      to be applied and results reported to highlight acute deviations in A1C. Such
      procedures will aid the attainment of the clinical quality requirements and give
      appropriate results for audit purposes.

PMID- 14687444
TI  - A comparison of the therapeutic efficacy and tolerability of etoricoxib and
      diclofenac in patients with osteoarthritis.
AB  - OBJECTIVE: To evaluate and compare the efficacy and tolerability of etoricoxib
      and diclofenac in patients with osteoarthritis of the knee or hip. METHODS: In
      this 6-week double-blind, active comparator controlled, parallel-group study
      eligible osteoarthritis patients were randomised to receive either etoricoxib 60
      mg once daily (n = 256) or diclofenac 50 mg three times daily (n = 260). The
      primary study endpoint was the Western Ontario McMaster osteoarthritis index
      (WOMAC) pain subscale. Other endpoints included were the WOMAC stiffness and
      physical function subscales, and the Patient's Global Assessment of Response to
      Therapy (PGART) questionnaire. Early efficacy was evaluated using WOMAC first
      question (pain walking on a flat surface) and PGART 4 h after the morning dose of
      each drug on days 1 and 2. Rescue medication (paracetamol) used was also
      recorded. The study was designed to show comparable efficacy between etoricoxib
      60 mg once daily and diclofenac 50 mg three times daily with respect to the
      primary endpoint and was conducted outside the United States at 67 centres in 29
      countries. RESULTS: Etoricoxib (60 mg once daily) was comparable in efficacy to
      diclofenac (150 mg daily) on all the above parameters. The one exception was in
      the assessment of early efficacy where etoricoxib demonstrated significantly
      greater benefit within 4 h of taking the first dose on the first day of therapy
      (p = 0.007) as evaluated by the percentage of patients with good or excellent
      (PGART) responses. The treatment effects of both drugs were similar by the time
      day 2 was reached and were sustained throughout the 6 weeks of therapy. Both
      treatments were generally well tolerated. CONCLUSIONS: Etoricoxib is clinically
      effective in the therapy of osteoarthritis providing a magnitude of effect
      comparable to that of the maximum recommended daily dose of diclofenac. The onset
      of clinical benefit with etoricoxib on day one is more rapid than that of
      diclofenac. Both drugs were generally well tolerated.

PMID- 14687445
TI  - Open-label study of mirtazapine orally disintegrating tablets in depressed
      patients in the nursing home.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of mirtazapine orally
      disintegrating tablets in depressed, elderly nursing home residents, under
      naturalistic study conditions. METHODS: In this open-label 12-week study,
      mirtazapine orally disintegrating tablets (15-45 mg/day) were administered to
      patients > or =70 years old with physician-diagnosed depression and a Mini-Mental
      State Examination (MMSE) score > or =10. Patients with medical comorbidities,
      cognitive impairment and/or concomitant medications were enrolled if they met
      study inclusion criteria and had illnesses and/or medication dosages that were
      considered stable. Assessments were performed at baseline by physicians and at
      days 14, 28, 56, and 84 (or early termination) by physicians or nurse
      coordinators using the Clinical Global Impression (CGI) scale, the 16-item
      Hamilton Rating Scale for depression (Ham-D-16 (the standard 17-item scale minus
      item 14)), and the Cornell Scale for Depression in Dementia (CSDD). Tolerability
      was evaluated based on treatment-emergent adverse events. RESULTS: A total of 119
      patients in the intent-to-treat (ITT) group were treated with mirtazapine orally
      disintegrating tablets (mean daily dose: 19.4 mg) and evaluated for efficacy. At
      endpoint, 54% of patients in the ITT group showed CGI-I response (defined as a
      CGI-I score of 1 or 2 ('very much' or 'much' improved) and 47% were Ham-D-16
      responders (defined as decrease from baseline of at least 50% in Ham-D-16 total
      score). CSDD mean scores and Ham-D-16 mean total scores demonstrated a
      progressive decrease from baseline to trial completion. The decrease in Ham-D
      scores from baseline to day 84 was statistically significant (p < 0.0001). Mean
      changes from baseline to day 84 were -6.6 +/- 6.9 (CSDD score) and -7.9 +/- 7.4
      (Ham-D-16 total score). Ham-D Factor I, Factor VI and item 1 scores also
      decreased. Fourteen of 124 patients in the all-subjects-treated (AST) group
      (11.3%) discontinued prematurely due to adverse events. The most frequently
      occurring adverse events were urinary tract infection (19%), accidental injury
      (18%), fall (18%), somnolence (12%), and upper respiratory infection (12%). Mean
      body weight increased by 0.7 +/- 2.25 kg (1.54 +/- 5 lb) from baseline to day 28,
      and by 1.3 +/- 3.36 kg (2.86 +/- 7.4 lb) from baseline to day 84. CONCLUSIONS:
      The results suggest that mirtazapine orally disintegrating tablets provide
      antidepressant efficacy and are a relatively well-tolerated treatment for
      depression in this patient population of elderly nursing home residents with
      medical and cognitive comorbidities.

PMID- 14687446
TI  - Sildenafil citrate does not affect cardiac contractility in human or dog heart.
AB  - OBJECTIVE: This study evaluated whether sildenafil citrate, an oral treatment for
      erectile dysfunction and a selective inhibitor of phosphodiesterase type 5 (PDE5)
      with modest vasodilating properties, affects cardiac contractility in vitro.
      RESEARCH DESIGN AND METHODS: Slices of freshly obtained human (n = 2) or dog (n =
      3) atrial appendage were suspended in organ baths containing Krebs-Ringer
      bicarbonate buffer (pH 7.4, 37 degrees C) bubbled continuously with 95% O2 and 5%
      CO2, and isometric tension was recorded using a Gould physiograph. Contractions
      were elicited by 1-Hz electric pacing. After 15 min of equilibration, 1 microM
      sildenafil was added to the bath, followed 15 min later (human and dog) by 5
      microM epinephrine, an inotropic agent, and 10 min later (dog) by 88 microM 3
      isobutyl-1-methylxanthine (IBMX), a nonselective PDE inhibitor. In a separate
      experiment, cyclic guanosine monophosphate levels and PDE, protein kinase G, and
      protein kinase A activities were determined. RESULTS: Addition of 1 microM
      sildenafil to isolated dog or human atrial tissue had no significant effect on
      force of cardiac contraction, whereas epinephrine produced a robust increase in
      contractile force in the same muscle strip. The addition of IBMX produced a
      marked stimulation of contractile force in dog atrial tissue. Very low amounts of
      PDE5 were found in extracts of human heart, consistent with its known primary
      location in the smooth muscle of systemic vasculature. CONCLUSIONS: Sildenafil is
      unlikely to directly produce inotropic effects on cardiac muscle in patients
      being treated for erectile dysfunction.

PMID- 14687447
TI  - Comparison of lenograstim and filgrastim on haematological effects after
      autologous peripheral blood stem cell transplantation with high-dose
      chemotherapy.
AB  - OBJECTIVE: To compare the efficacy of lenograstim and filgrastim on
      haematological recovery following an autologous peripheral blood stem cell
      transplantation (PBSCT) with high-dose chemotherapy. METHODS: A retrospective
      case-controlled study. RESULTS: Absolute neutrophil count (ANC) recovery above
      0.5 x 10(9)/l and white blood cell (WBC) recovery above 4 x 10(9)/l for 3
      consecutive days was achieved earlier with filgrastim than with lenograstim
      ((13.2 +/- 8.0 vs 19.0 +/- 10.0 days, p = 0.004), (16.9 +/- 9.7 vs 29.9 +/- 16.6
      days, p = 0.001), respectively). The platelet recovery above 20 x 10(9)/l was
      also achieved earlier with filgrastim than with lenograstim (19.5 +/- 11.6 vs
      27.2 +/- 13.8 days, p = 0.006). Furthermore, filgrastim-treated patients received
      fewer days of granulocyte colony simulating factor (G-CSF) administration (12.5
      +/- 7.0 vs 18.6 +/- 8.5 days, p = 0.001) and spent less time in hospital (23.7 +/
      10.9 vs 32.0 +/- 17.6 days, p = 0.009). Duration of antibiotic administration
      was also significantly shorter in the filgrastim group (13.6 +/- 7.6 vs 29.1 +/-
      19.8 days, p = 0.001). CONCLUSION: In patients undergoing PBSCT following high
      dose chemotherapy, filgrastim significantly reduced the duration of neutropenia,
      thrombocytopenia and days of G-CSF administration, and led to earlier hospital
      discharge compared with lenograstim.

PMID- 14687448
TI  - Chronic venous insufficiency: the effects of health-care reforms on the cost of
      treatment and hospitalisation--an Italian perspective.
AB  - OBJECTIVES: This study evaluated the evolution of chronic venous insufficiency
      (CVI)-related costs in Italy over 8 years by focusing on the impact of the
      Italian health-care reforms (drug de-reimbursement) of 1993-94. RESEARCH AND
      DESIGN METHODS: The global cost of CVI to the Italian health system (Sistema
      Sanitario Nazionale, SSN) was divided into three sub-costs: hospitalisation, GP
      consultation and prescription costs. Indirect costs, such as loss of working
      days, were not included. CVI-related hospitalisation costs included inpatient
      treatment for varicose veins, venous leg ulcers and other venous disorders. They
      were calculated using the US-derived system, Diagnosis Related Group (DRG), used
      in Italian hospitals. Calculations for the whole country were based on figures
      determined for the Lombardy region and extrapolated. It was considered reasonable
      to assume that this region was representative of the whole of Italy. CVI-related
      GP consultation and prescription costs were derived from Intercontinental Medical
      Statistics (IMS) data. These costs, pre- and post-reforms, were determined and
      compared to evaluate the impact of the reforms on CVI-related expenditure.
      RESULTS: Pre-reforms CVI-related costs analysis (1991): hospitalisations, 210
      million Euro; GP consultations, 35.4 million Euro; prescriptions,115 million Euro
      . The total CVI-related direct costs (i.e. CVI diagnosis and management) were
      360.4 million Euro. Post-reforms CVI-related costs analysis (1999):
      hospitalisations, 288 million Euro; GP consultations, 13 million Euro;
      prescriptions, 83 million Euro . The total CVI-related direct costs were 384
      million Euro. Hospitalisation costs increased predominantly due to an increase in
      hospitalised patients. GP consultation and prescription costs decreased
      predominantly due to drug de-listing. The 23.6 million Euro increase in CVI
      management expense, post-reforms, was due to cost-redistribution from
      prescriptions and GP consultations to hospitalisations. CONCLUSION: Short-term
      goals were achieved by the reforms, but long-term expectations were not. Drug de
      reimbursement reduced both drug costs for the SSN and the number of GP
      consultations. Fewer patients were treated overall (mostly with advanced
      disease), with consequent disease worsening and increase in complications. An
      increase in CVI-related hospitalisation resulted. In contrast, preventative
      measures, including patient education and prophylactic treatment, exhibit both
      clinical and cost effectiveness. Larger studies are required to confirm these
      preliminary results.

PMID- 14687449
TI  - Utilization patterns and net direct medical cost to Medicaid of irritable bowel
      syndrome.
AB  - BACKGROUND: Patients with irritable bowel syndrome are frequent users of the
      health care system. DESIGN AND METHODS: This retrospective matched case-control
      study assessed the economic impact of irritable bowel syndrome on the Medicaid
      program by comparing the health care utilization and expenditures of Medicaid
      patients with irritable bowel syndrome in California and North Carolina with age
      , sex-, and race-matched control groups without the syndrome. RESULTS: Average
      annual Medicaid expenditures per case of diagnosed irritable bowel syndrome were
      2952 dollars and 5908 dollars in California and North Carolina, respectively;
      corresponding unadjusted net incremental expenditures were 962 dollars and 2191
      dollars, respectively. In both states, patients with irritable bowel syndrome
      incurred greater costs than controls for physician visits, outpatient visits, and
      prescription drugs. CONCLUSIONS: Irritable bowel syndrome was shown to impose an
      economic burden on the Medicaid program. The cost of treating patients with
      irritable bowel syndrome is higher than the cost of treating matched ambulatory
      Medicaid recipients without the condition.

PMID- 14687450
TI  - Disintegration/dissolution profiles of copies of Fosamax (alendronate).
AB  - OBJECTIVE: Poor quality has been reported for some generics and other copies of
      original products. We performed a pilot study to compare the
      disintegration/dissolution profiles of FOSAMAX (alendronate) 70 mg tablets with
      those of copies of FOSAMAX that were manufactured outside the United States.
      RESEARCH DESIGN AND METHODS: We used the standard United States Pharmacopeia
      (USP) disintegration method to evaluate FOSAMAX 70 mg tablets and 13 copies. At
      least 12 (n = 12) dosage units were tested for each product (except Fosmin, n =
      10). The dissolution profiles of FOSAMAX and one representative copy were also
      compared. RESULTS: Nine copies (Osteomax, Defixal, Fosmin, Endronax, Osteomix,
      Genalmen, Fixopan, Osteoplus, and Fosval) disintegrated two- to ten-fold faster
      than FOSAMAX. Three other copies (Neobon, Regenesis, and Ostenan) disintegrated
      at least five-fold slower than FOSAMAX. Neobon is a softgel capsule, so special
      consideration was given to this different dosage form. One copy (Arendal) did not
      fall into either category but exhibited potentially large inter- and intra-lot
      variability. Dissolution of alendronate from Regenesis lagged behind that from
      FOSAMAX. CONCLUSION: Slower disintegration may reduce efficacy because
      bisphosphonates must be taken in the fasting state and contact with food or even
      certain beverages severely reduces bioavailability. Faster disintegration (or the
      use of gel-caps or other alterations to the drug formulation) could increase the
      risk of esophagitis, an adverse event associated with prolonged contact of the
      esophagus with bisphosphonates. These disintegration and dissolution results
      suggest that important differences may exist between FOSAMAX and its copies with
      regard to bioavailability, pharmacokinetics, and clinical efficacy and safety
      profiles. Additional testing is warranted to evaluate the pharmacokinetics and
      clinical safety of these copies.

PMID- 14687451
TI  - Common cold and influenza symptom management: the use of pharmacokinetic
      considerations to predict the efficacy of a twice-daily treatment for colds and
      flu.
AB  - OBJECTIVE: The objective of the two pharmacokinetic studies reported here was to
      compare the relative bioavailability of an ibuprofen/pseudoephedrine modified
      release capsule with each of the active ingredients given alone as standard
      formulations. STUDY DESIGN: Evaluation of two open, randomised, cross-over
      studies, one single dose and one multiple dose, in healthy male volunteers.
      METHODS: Healthy volunteers were randomised in a cross-over design to single or
      multiple doses of a combination of ibuprofen (600 mg) plus pseudoephedrine (90
      mg) in a slow-release formulation and the individual active products alone as
      standard formulations; ibuprofen 400 mg, pseudoephedrine 60 mg. RESULTS: The
      single-dose study demonstrated that the bioavailabilities of ibuprofen and
      pseudoephedrine achieved with the slow-release formulation were not significantly
      different from those with standard tablets of each ingredient alone. In addition,
      mean plasma levels of ibuprofen predictive of clinical efficacy were achieved
      within 0.5-1 h and lasted for 10-12 h thereafter. The time required to reach
      clinically effective blood levels of pseudoephedrine was longer, starting at
      approximately 2 h. However, the plasma levels predicted that the clinical effect
      would then last for at least a further 12 h. Trough levels from the multiple-dose
      study showed that clinically relevant analgesic and decongestant plasma levels
      were maintained for 24 h during twice-daily dosing. The slow-release formulation
      was well tolerated with only mild adverse events. CONCLUSIONS: Blood levels would
      predict that the present slow-release formulation of ibuprofen plus
      pseudoephedrine should offer reliable day and night control of cold and flu and
      sinus symptoms and be associated with a favourable safety profile.

PMID- 14687453
TI  - Attentional difficulties in children: weakness in executive function or problems
      in coping with difficult tasks?
AB  - Two groups of children, one with good attention and one with poor attention, as
      rated by teachers, carried out a computerized visual search task. There were no
      differences between groups on an easy search for a single target, but when the
      task was made more difficult by including foils very similar to the targets or
      requiring alternating search for two different targets, the poor attention group
      made significantly more errors than the good attention group. The nature of these
      increases in errors was examined to discover whether they were due to errors
      specifically on the foils similar to the targets and errors due to failure to
      alternate. It was found that as well as making more errors of these types, the
      children with poor attention also showed a greater increase in other types of
      error (shape confusions, repetitions etc.) from the simple task to the more
      difficult ones. It is concluded that these findings do not support an explanation
      of poor attention solely in terms of weaknesses in specific executive functions,
      but suggest that supplementary or alternative explanations are needed, for
      example reduced processing capacity or problems in motivation or arousal when
      coping with difficult tasks.

PMID- 14687454
TI  - Stereotypes and crossed-category evaluations: the case of gender and science
      education.
AB  - A sample of UK adolescents (n = 1140), grouped by sex and liking of science,
      evaluated themselves, and girl and boy targets who did or did not like science,
      on masculine, feminine and gender non-specific traits. Contrary to sociological
      concerns about the masculine image and appeal of science, those who liked science
      more rated themselves more positively on feminine and gender non-specific-but not
      masculine-traits. The girl target was rated lower on feminine traits if she liked
      science, but the boy was rated higher on feminine traits if he liked science.
      Target ratings also showed in-group enhancement based on liking of science, and a
      'black sheep' effect: those who liked science less discriminated against the same
      sex target who liked science, especially on gender in-group relevant traits. We
      argue that gender differences in science education should be attributed partly to
      subjective group dynamics and not solely to images of science.

PMID- 14687455
TI  - Reassessing the dimensionality of the moral emotions.
AB  - The dimensionality of the moral emotions was tested to examine whether
      theoretical distinctions between specific emotions were empirically supported. A
      total of 720 drink-driving offenders indicated the degree to which they
      experienced feelings associated with the moral emotions, in an interview
      conducted after attending court or a restorative justice conference. Expected
      distinctions between shame and guilt were not found. Instead the principal
      components analysis identified three factors: shame-guilt, embarrassment
      exposure, and unresolved shame. The results also show that shame-guilt was
      related to higher feelings of empathy and lower feelings of anger/hostility. It
      is concluded that differences between shame and guilt may be overstated.
      Furthermore, it is suggested that the relationship between situational
      experiences of shame and the disposition to feel it may be more complicated than
      initially thought.

PMID- 14687456
TI  - Adults' versus children's performance on the Stroop task: interference and
      facilitation.
AB  - Stroop tasks (Stroop, 1935) present stimuli having two dimensions, and
      participants respond to one dimension whilst ignoring the other. The two
      dimensions are made congruent, incongruent or neutral with respect to one
      another. Many claim that 'Stroop interference' is higher in children than in
      adults. However, taking interference as the difference between the incongruent
      condition and the neutral condition, with interference within the congruent
      condition itself termed the 'incongruity effect' then surprisingly few studies
      directly address this issue. Also, there is recent debate as to whether the
      'facilitation effect' (the contrast between the congruent and neutral conditions)
      is just the opposite of interference. The present investigation (N = 31)
      concerned a direct comparison between children and adults. Although the
      incongruity effect reduced with age, interference did not. However, facilitation
      was far higher in children than in adults. The groups' opposite
      facilitation/interference asymmetry was used to examine the recent claim that
      these derive from inadvertent word-reading and suppression of semantic
      activation, respectively; rather than solely from the latter.

PMID- 14687457
TI  - Can we correctly perceive the reaching range of others?
AB  - Little is known about our ability to predict the motor capacities of other
      people. This study explored how observers perceive the reaching range of another
      person by asking them to judge the reachability of a moving object. Experiments 1
      and 2 found that observers overestimated the reaching ranges of both short and
      tall people. Estimates were larger when objects moved towards rather than away
      from the person. Experiment 3 showed that perceived reaching range depended on
      the observer's viewing perspective. Compared with previous findings, these
      results suggest that observers use different cognitive operations to mentally
      simulate actions for themselves vs. others. They also inform the current debate
      about motor imagery and action understanding.

PMID- 14687458
TI  - Measurement of body size and shape perception in eating-disordered and control
      observers using body-shape software.
AB  - A disturbance in the perception of personal body size and shape is a key feature
      of both anorexia and bulimia nervosa, but it has proved difficult to quantify.
      Previous attempts have used methods like the distorting video technique (DVT),
      which alters an image by stretching the figure in either the X- or Y-axis. This
      is a poor representation of the way fat is added to or lost from the body, and
      the pattern of distortion provides a host of cues to the degree to which the
      image has been altered. To overcome these problems we have used a specially
      designed software system that uses biometric data based on real body shapes,
      instead of simply stretching or compressing images of bodies. This technique also
      allows individual body parts to be altered separately, so we can determine
      whether a specific body part is overestimated relative to others. We can also
      calculate the apparent body mass index (BMI) of our modified pictures, using the
      perimeter-area ratio (PAR). This allows us to compare an observer's actual BMI
      with that calculated for their estimated and ideal bodies. We tested 30 anorexic,
      30 bulimic and 137 control observers. Our results show that all three observer
      groups tend to overestimate their body size, but not significantly so. Both the
      control and bulimic observers prefer an ideal body with a BMI of 20, which is at
      the lower end of the 'normal' BMI range. However, the anorexics ideal BMI is 15,
      which is on the border between the emaciated and underweight BMI categories.

PMID- 14687459
TI  - Semantic priming in the name retrieval of objects and famous faces.
AB  - Researchers interested in face processing have recently debated whether access to
      the name of a known person occurs in parallel with retrieval of semantic
      biographical codes, rather than in a sequential fashion. Recently, Schweinberger,
      Burton, and Kelly (2001) took a failure to obtain a semantic context effect in a
      manual syllable judgment task on names of famous faces as support for this
      position. In two experiments, we compared the effects of visually presented
      categorically related prime words with either objects (e.g. prime: animal;
      target: dog) or faces of celebrities (e.g. prime: actor; target: Bruce Willis) as
      targets. Targets were either manually categorized with regard to the number of
      syllables (as in Schweinberger et al.), or they were overtly named. For neither
      objects nor faces was semantic priming obtained in syllable decisions; crucially,
      however, priming was obtained when objects and faces were overtly named. These
      results suggest that both face and object naming are susceptible to semantic
      context effects.

PMID- 14687460
TI  - The social context of musical success: a developmental account.
AB  - This paper brings together extensive data from 257 children to explore the
      relative importance of social-environmental factors during critical periods of
      children's musical development. The paper also presents preliminary findings from
      a follow-up of 20 of the most musically successful children 8 years later to
      determine which childhood factors predict differences in success as adult
      performers. Those children who continued to play an instrument started at an
      early age, had higher parental support in lessons, and had first teachers who
      were friendly but not too technically able. However, these factors alone were not
      sufficient to predict relative success in childhood. Successful childhood
      musicians also appear to need teachers who are 'not too relaxed' and also 'not
      too pushy' and they also need to do substantial amounts of practice. The follow
      up study suggested, though, that successful adult performers were not those who
      did the most practice; rather, the successful adults were those who took part in
      more concert activities in childhood, did more improvisation, and who had mothers
      at home in their early years. The results are discussed in relation to theories
      of musical development and the changing influences of parents, teachers and
      peers.

PMID- 14687461
TI  - Intelligence and class mobility in the British population.
AB  - Performance on intelligence tests is known to be associated with class mobility,
      with high scorers tending to move up the socio-economic hierarchy, and low
      scorers tending to move down. However, much remains unknown about the
      association. It is possible that the importance of intelligence varies across
      different occupational areas, or that there is friction acting against mobility,
      such that a person from an underprivileged background would have to be more
      intelligent in order to reach a given position than someone who had had greater
      social advantage. Data from a longitudinal study of a broad, socially
      representative cohort of the British population (the NCDS) are used to
      investigate these questions. The results show that intelligence test scores in
      childhood are associated with class mobility in adulthood uniformly across all
      social classes. There is no evidence that those from underprivileged backgrounds
      have to be disproportionately able in order to reach the professional classes.
      The study reveals an apparently high level of social mobility and meritocracy in
      contemporary Britain.

PMID- 14687462
TI  - Long-term effects of imidapril on calcium and potassium currents in rabbit left
      ventricular hypertrophic myocytes.
AB  - OBJECTIVE: To investigate the long-term effects of imidapril (IMI) on action
      potential and calcium and potassium currents in rabbit left ventricular
      hypertrophic myocytes. METHODS: Rabbits were randomly divided into three groups:
      IMI-treated, hypertrophic and sham-operated control groups. Cardiac hypertrophy
      was induced in hypertrophy group by partial ligation of the abdominal aorta. In
      the IMI-treated group, the rabbits were administered IMI (1.5 mg x kg(-1) x d(
      1)) for 8 weeks after surgery. In the sham-operated control group, the animals
      underwent an abdominal laparotomy without further procedure. Whole-cell patch
      clamp technique was used to record ionic currents. RESULTS: Membrane capacitance
      was larger in hypertrophic cells than in sham-operated cells or IMI-treated
      cells. Action potential duration was lengthened in hypertrophic cells and was
      remarkably shortened by IMI. The density of ICa, L was reduced from 12.8 +/- 0.7
      pA/pF in the sham-operated cells, to 7.7 +/- 0.8 pA/pF in hypertrophic cells,
      while it resembled the control cells after IMI treatment (11.9 +/- 1.0 pA/pF).
      After IMI treatment, the density of I(Ks,tail) was enhanced from 2.5 +/- 0.1
      pA/pF in hypertrophic cells to 4.7 +/- 0.6 pA/pF (n = 7, P < 0.01), which was
      similar to the sham-operated cells. The densities of Ito and IK1 were
      significantly increased in IMI-treated cells, from 3.8 +/- 0.4 pA/pF and 3.7 +/-
      0.5 pA/pF in the hypertrophic cells to 6.4 +/- 0.8 pA/pF and 6.5 +/- 0.3 pA/pF,
      respectively, but the IKr densities were not different in the three groups.
      CONCLUSION: IMI could reverse the increase in membrane capacitance in
      hypertrophic cells, shorten action potential duration, and increase the densities
      of ICa, L, IKs, Ito and IK1 in hypertrophic cells.

PMID- 14687463
TI  - Changes in delayed rectifier K+ channel function and its regulation by protein
      kinase C pathway in bronchial myocytes from asthmatic rats.
AB  - OBJECTIVE: To investigate changes in the delayed rectifier K+ channel (Kv)
      function and the regulation of Kv by the protein kinase C (PKC) pathway in
      bronchial myocytes from asthmatic rats. METHODS: The Kv currents and membrane
      potentials in bronchial myocytes from asthmatic rats and from controls were
      observed, using whole cell voltage- and current-patch clamp techniques. RESULTS:
      Bronchial myocytes from asthmatic rats showed a significant reduction in Kv
      current density (51.6 +/- 9.4 pA/pF, n = 14, P < 0.01) in comparison with those
      from control rats (72.4 +/- 12.3 pA/pF, n = 14) at + 50 mV. The current-voltage
      relationship curve exhibited a significant downward shift. Bronchial myocytes
      from asthmatic rats had no significantly different capacitances (P > 0.05), but
      had more positive membrane potential (P < 0.01) compared with those from
      controls. 1 micro mol/L phorbol 12-myristate 13-acetate, a PKC activator, caused
      an obvious reduction in Kv-current density (P < 0.01) and a significant downward
      shift in the current-voltage relationship curve, an effect which was partly
      abolished by 1 micro mol/L Ro31-8220 (a PKC inhibitor); 1 micro mol/L phorbol 12
      myristate 13-acetate caused more positive membrane potential (Em), from -36.8 +/-
      5.7 mV to -30.4 +/- 7.3 mV, in rat bronchial myocytes (P < 0.05). This effect was
      partly abolished by 1 micro mol/L Ro31-8220. CONCLUSIONS: Bronchial myocytes from
      asthmatic rats have inhibited Kv function, more positive membrane potential, and
      higher excitability, all of which can also be induced by PKC activation. These
      characteristics may contribute to the development of airway hyperreactivity in
      asthma.

PMID- 14687464
TI  - Carbon monoxide inhibits proliferation of pulmonary smooth muscle cells under
      hypoxia.
AB  - OBJECTIVE: To investigate the expression of inducible heme oxygenase (HO-1) gene
      in pulmonary artery smooth muscle cells (PASMCs) exposed to hypoxia, and the
      influence of carbon monoxide (CO) on the proliferation of PASMCs under hypoxic
      conditions. METHODS: Primary culture of rat PASMCs were passed every 3 days, and
      the 3 - 5 passages were used. After exposure to hypoxic conditions (95% N2, 5%
      CO(2)) 0, 12, 24 and 48 hours, the level of HO-1 mRNA was examined by reverse
      transcriptase polymerase chain reaction (RT-PCR). The volume of COHb in the
      medium was measured spectrophotometrically. The cyclic guanosine mono-phosphate
      (cGMP) concentration of cell extracts was determined by radioimmunoassay. PASMCs
      were divided into 5 groups, cultured under normoxia and hypoxia and treated with
      hemin, hemoglobin (Hb) and exogenous CO respectively. Then 3-(4, 5
      cimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) colorimetric assay
      and immunocytochemical staining were used to study the energy metabolism and the
      expression of proliferating cell nuclear antigen (PCNA) in PASMCs. Flow cytometry
      was used to analyze the cell cycle of PASMCs. RESULTS: After exposure to hypoxic
      conditions for 12, 24, and 48 hours, the HO-1 mRNA increased by 2.7%, 5.7% and
      27.1% respectively (P < 0.01). The carboxy-hemoglobin (COHb) in the medium
      increased by 13.8%, 31.0% and 93.1% (P < 0.01); the cGMP concentrations were 2.7,
      4.0 and 6.8-fold compared with the control group (P < 0.01 and P < 0.05). In
      comparison with the control group, the value of MTT colorimetric assay, the
      immunocytochemical staining of PCNA and the percentages of PASMCs in S and G2M
      phases in the hypoxic group were significantly higher (P < 0.01). After treatment
      with Hemin and CO, the results of the above analysis decreased significantly (P <
      0.01 and P < 0.05), but increased significantly after treatment with Hb (P < 0.01
      and P < 0.05). CONCLUSIONS: The expression of HO-1 gene in PASMCs is upregulated
      by hypoxia and the production of endogenous CO is elevated as well. The
      endogenous CO suppresses the proliferation of PASMC in an autocrine way. Both the
      induction of endogenous CO by Hemin and the treatment with exogenous CO can
      suppress the proliferation of rat PASMCs of under hypoxic conditions.

PMID- 14687465
TI  - Impact of acute vivax malaria on the immune system and viral load of HIV-positive
      subjects.
AB  - OBJECTIVE: To explore the mechanisms of malariotherapy for human immunodeficiency
      virus (HIV)-infected patients and to identify which stage(s) of HIV infection is
      suitable for the treatment of malariotherapy. METHODS: Therapeutic acute vivax
      malaria was induced and terminated after 10 fever episodes in 12 HIV-1-infected
      subjects: Group 1 (G1) had 5 patients with CD(4) T-cell counts >or=500/ micro l
      at baseline, Group 2 (G2) had 5 patients with CD4 at 499 - 200/ micro l and Group
      3 had 2 patients with CD(4) < 200/ micro l (not included in statistical
      analysis). Enzyme-Linked-Immuno-Sorbent Assay (ELISA) was used to measure plasma
      levels of cytokines and soluble activation markers. Flow cytometry was used to
      measure levels of lymphocyte subsets and phenotypes and CD(4) cell apoptosis.
      Bayer bDNA assay was used to test plasma levels of HIV-1 RNA (viral load).
      Samples were taken and tested twice before malaria (baselines), three times
      during malaria and seven times after termination of malaria (at day 10 and 1, 3,
      6, 12, 18 and 24 months). RESULTS: Levels of plasma tumor necrosis factor-alpha
      (TNF-alpha), soluble TNF-alpha receptor-2 (sTNF-RII), neopterin (NPT) and soluble
      IL-2 receptor (sIL-2R) significantly increased during malaria and sharply reduced
      to baselines post malaria in all groups. Stronger responses of the aforementioned
      factors were seen in G2 than in G1 during malaria (P = 0.081, 0.001, 0.013,
      0.020). CD4 count and percentage; CD(4)/CD(8) ratio and CD(25)(+) and
      CD(4)(+)CD(25)(+) percentages increased but HLA-DR+ percentage decreased either
      during or post malaria in G2. Most G2 patients experienced sustained increase but
      most G1 patients underwent natural history decline of CD(4) counts and
      percentages during 2-year follow-up. Percentage of apoptotic CD(4) cells
      decreased post malaria in all groups. G3 patients had weaker immune responses,
      however, one advanced AIDS patient in this group experienced clinical improvement
      after malariotherapy. Most of the 12 patients experienced increase of HIV viral
      load during malaria but the viral load returned to baseline levels 1 - 3 months
      after cure of malaria and remained near baseline levels for up to two years.
      CONCLUSIONS: Part of the mechanisms of malariotherapy is to induce high levels of
      cytokine activities and subsequently the changes of T-lymphocyte subsets and
      phenotypes in HIV-infected patients. These findings suggest that malariotherapy
      may treat HIV-1-infected patients whose CD4 baselines are in the range of 500 -
      200/ micro l.

PMID- 14687466
TI  - Accuracy of three diagnostic tests used alone and in combination for detecting
      Helicobacter pylori infection in patients with bleeding gastric ulcers.
AB  - OBJECTIVE: Accuracy of diagnostic methods for detecting Helicobacter pylori (H.
      pylori) infection among patients with bleeding peptic ulcers has not been
      thoroughly investigated. The aim of this study was to compare the diagnostic
      tests and their combined usage in detection of H. pylori infection in patients
      with bleeding gastric ulcers and without the use of nonsteroidal anti
      inflammatory drugs. METHODS: A total of 57 patients who presented with bleeding
      gastric ulcers by endoscopy were enrolled. The status of H. pylori was identified
      by performing the rapid urease test (RUT), histology and (13)C-labeled urea
      breath test (UBT). The criteria for having H. pylori infection was a minimum of
      two positive tests. RESULTS: The prevalence of H. pylori infection in our patient
      group was 80.7%. Among the three tests used: RUT, histology, and UBT,
      sensitivities were 56.5%, 97.8% and 100%, while specificities were 100%, 45.5%
      and 81.8%, respectively. The overall accuracies of the tests were 78.3%, 71.6%
      and 90.9%, respectively. Although UBT obtained significantly higher accuracy than
      histology (P = 0.02) as opposed to RUT (P = 0.11), UBT had significantly higher
      sensitivity than RUT (P < 0.001). In terms of combining any two of the three
      tests, more accuracy (98.9%) was achieved when both UBT and histology were used
      to confirm the diagnosis of the other. Conversely, failure to use combined tests
      generated the potential of missing a proper H. pylori diagnosis. CONCLUSIONS: UBT
      is superior to the other two tests in bleeding gastric ulcers. RUT lacks
      sensitivity for detection of H. pylori infection. However, the concomitant use of
      UBT and histology seems to be more accurate when gastric ulcers present with
      bleeding.

PMID- 14687467
TI  - Cyclosporine A in treatment of membranous lupus nephropathy.
AB  - OBJECTIVE: To investigate retrospectively the efficacy of cyclosporine A (CsA) in
      the treatment of membranous lupus nephropathy (MLN). METHODS: Twenty-four
      patients with systemic lupus erythematosus (SLE) and biopsy-proven MLN were
      treated with CsA in combination with prednisone. CsA was given at a starting
      dosage of 5 mg x kg(-1) x d(-1) for 3 months, with a 1 mg x kg(-1) x d(-1)
      reduction every month and then maintained at a dosage of 2 mg x kg(-1) x d(-1).
      The dosage of oral prednisone differed from person to person according to levels
      of extra-renal activity. Clinical efficacy and adverse reactions were
      retrospectively analyzed. Complete remission was defined as having a urinary
      proteinuria level (Upr) of < 0.4 g/d, and normal serum albumin and serum
      creatinine (SCr) levels, without SLE activity. Partial remission was defined as
      having a UPr decrement > 50% of baseline value and a serum albumin value of 30 -
      35 g/L, without SLE activity. No response was defined as having a Upr decrement <
      50% of baseline value and > 2.0 g/d, or as a deterioration of renal function, or
      as having active SLE. RESULTS: One patient could no longer undergo follow-up, and
      the other 23 patients were treated with CsA and followed up for 6 - 36 months
      (mean 16.8 +/- 8.4 months). The mean starting dosage of CsA was 4.7 +/- 0.5) mg x
      kg(-1) x d(-1) and the trough level of the whole blood CsA was 248 +/- 110) micro
      g/L. Twelve patients (52.2%) achieved complete remission, 10 patients (43.3%)
      achieved partial remission after CsA treatment, and one patient showed no
      response. At different CsA treatment timepoint, the complete remission rates were
      17.4% (3rd month), 21.7% (6th month), 40% (12th month), 88.9% (18th month) and
      100% (24th month) respectively. SCr elevation, when within a normal limit was not
      observed in most patients during early CsA administration, and at the end of the
      follow-up all the patients had a normal SCr. Relapse occurred in 33.3% of the
      patients after withdrawing CsA for 4 - 24 months. No chronic CsA renal toxicity
      was observed in 4 patients who had a repeat renal biopsy after CsA treatment for
      6 - 24 months. CONCLUSIONS: CsA could be regarded as an effective therapy for
      patients with membranous lupus nephropathy, but its adverse effects, especially
      its nephrotoxicity, should be carefully monitored during CsA treatment.

PMID- 14687468
TI  - Adriamycin increases podocyte permeability: evidence and molecular mechanism.
AB  - OBJECTIVE: To investigate the increased podocyte permeability by evidence of
      adriamycin (AD) and its molecular mechanism. METHODS: In this study, we explored
      the direct effects of AD on cultured mouse podocytes and the potential protection
      effects of Dexamethasome (Dex). RESULTS: After 24-hour AD (5 x 10(-7) mol/L)
      treatment, albumin passage through podocyte monolayers was increased by 2.27-fold
      (P < 0.01). AD caused a 62% decrease in Zonula Occluden-1 (ZO-1) protein (P <
      0.05), suggesting that AD might increase podocyte permeability by disrupting
      tight junctions. Dex (1 x 10(-6) mol/L), co-administered with AD, protected
      podocytes from AD-induced increased albumin passage. This may be linked with an
      increased P-cadherin protein level to 1.93 fold of control (P < 0.01).
      CONCLUSIONS: AD has a direct, detrimental effect on podocyte permeability,
      probably through disrupting tight junctions; Dex could protect against AD-induced
      high podocyte permeability by upregulating adherent protein P-cadherin.

PMID- 14687469
TI  - PET imaging of brain function while puncturing the acupoint ST36.
AB  - OBJECTIVE: To explore the experimental method of obtaining position emission
      tonogiaphy (PET) imaging evidence of changes in cerebral function by puncturing
      the Stomach 36 (ST36, Zusanli) acupoint. METHODS: Data on changes of cerebral
      glycometabolism were obtained from six healthy male volunteers with positron
      emission tomography. Visual experimental evidence, as well as statistical
      parametric mapping (SPM), was gathered while puncturing the ST36 (Zusanli, right
      leg) acupoint. RESULTS: There was increased glycometabolism in the hypothalamus,
      head of the caudate nucleus, temporal lobe, the sinistral cerebellum, postcentral
      gyrus, and brain stem while the acupoint ST36 was being punctured. CONCLUSIONS:
      Acupuncture on ST36 can lead to increase in glycometabolism in the vegetative
      nerve centers, which is correlated with gastric function. Visual experimental
      evidence of ST36 acupuncturing on functional gastrointestinal disorder was
      obtained in our study.

PMID- 14687470
TI  - Aortic arch and intra-/extracranial cerebral arterial atherosclerosis in patients
      suffering acute ischemic strokes.
AB  - OBJECTIVE: To determine the distribution of aortic arch and intra/extracranial
      cerebral arterial atherosclerosis in Chinese patients who had suffered acute
      ischemic strokes. METHODS: Eighty-nine patients with acute ischemic strokes were
      included in this study. Transesophageal echocardiography (TEE) was used to
      evaluate potential sources of embolisms in the aortic arch and in the heart;
      duplex ultrasound was used for the carotid artery; and intracranial Doppler (TCD)
      imaging was used for the middle cerebral artery (MCA), anterior cerebral artery
      (ACA), posterior cerebral artery (PCA), and basilar artery (BA). An
      atherosclerotic lesion in the aortic arch was defined as normal (0); mild plaque
      (1); moderate plaque (2); and protruding plaque or mobile plaque (3). A lesion in
      the carotid artery was considered a plaque if the maximal carotid plaque
      thickness was 1.2 mm. TCD results were deemed abnormal if flow velocity was
      either greater or lower than normal, and, in the case of the MCA, if an asymmetry
      index above 21% was measured. RESULTS: Of the 89 patients, 52 (58.43%) patients
      showed evidence of aortic arch atherosclerosis (AAA), including 11 (12.36%)
      patients graded mild, 18 (20.22%) patients graded moderate, and 23 (25.84%)
      patients graded severe. Of the 23 patients with severe AAA, AAA was determined to
      be an important potential embolic source in 14 patients. Forty-nine (50.56%)
      patients had carotid arterial plaques (CAPs). The incidence of carotid plaques
      was higher among patients with AAA than among patients without AAA (71.15% vs
      21.62%, OR = 3.291, 95% CI = 1.740 - 6.225, P < 0.001). TCD abnormalities
      affecting the MCA were found in 54 (60.67%) patients. Differences in incidence of
      TCD abnormalities between patients with AAA and without AAA (69.23% vs 48.65%)
      were not significant (OR = 1.423, 95% CI = 0.976 - 2.076, P = 0.05). There was a
      higher incidence of AAA in older, male patients with a history of diabetes and
      smoking. CONCLUSIONS: AAA is an important potential source of cerebral embolic
      strokes. The presence of carotid arterial plaques correlates with AAA incidence.
      Most of carotid artery lesion were plaques other than severe stenosis, it may be
      the character of carotid atherosclerosis of stroke patients. It appears that
      atherosclerosis does not mainly occur in the intracranial arteries in stroke
      patients as thought before. Aged, male, diabetes, and smoking are important risk
      factors to the AAA.

PMID- 14687471
TI  - Clinical and experimental pathology of Moyamoya disease.
AB  - OBJECTIVE: To investigate the etiology, pathology, and mechanism of pathogenesis
      of Moyamoya disease. METHODS: A total of 15 human autopsies were analyzed. In
      addition, in order to create an animal model of the disease, 21 Japanese rabbits
      were divided randomly into two groups and subjected to injections of horse serum
      either intravenously or locally in the area of the sympathetic ganglia.
      Pathological and immunohistochemical characteristics were observed. RESULTS: The
      pathological features of the autopsies and the animal models both involved intima
      hyperplasia and stenosis or even occlusion of the lumen in the terminal ends of
      the internal carotid artery and the anterior and middle cerebral arteries.
      Disconnections or even breakages of the inner layer of the lumen were also
      observed, without an obvious inflammatory response. Hyperplasic smooth muscle
      cells of the medial membrane had extended inward through broken portions of the
      internal elastic lamina, with intima cell hyperplasia resulting in lumen
      stenosis. The hyperplastic vascular walls were positive for IgG and IgM.
      CONCLUSIONS: The etiology of Moyamoya disease may involve allergic angiitis. A
      possible mechanism is that proximal portions of the circle of Willis first
      develop chronic stenosis or occlusion, leading to compensatory small vessel
      proliferation, which perforates into the cerebral parenchyma.

PMID- 14687472
TI  - Relationship between expression of somatostatin receptors subtype 2 mRNA and
      estrogen and progesterone receptors in breast cancer.
AB  - OBJECTIVES: To observe the expression of somatostatin receptor subtype 2 (SSTR2)
      mRNA, and investigate the relationship between the expression of SSTR2 mRNA and
      the expressions of estrogen and progesterone receptors (ERs and PRs) in benign
      and malignant breast tissues. METHODS: Samples from a total of 23 breast
      carcinomas, 16 mammary hyperplasias, and 9 mammary fibroadenomas were analyzed.
      SSTR2 mRNA expression was examined by in situ hybridization using multiphase
      oligoprobes. ER and PR expressions were detected by immunohistochemical staining.
      A computerized image analysis system was utilized to estimate the relative
      content of SSTR2 mRNA. RESULTS: The rate of expression (87.0%) and relative
      content (0.47) of SSTR2 mRNA in breast cancer were higher than those in benign
      breast tissue (64%, 0.26) (P < 0.05). SSTR2 mRNA expression was closely
      correlated with ER and PR expressions in breast cancer (P < 0.05). SSTR2 mRNA was
      also positively correlated with ER expression in benign breast tissues.
      CONCLUSIONS: SSTR2 mRNA expression is higher or in benign breast tissues than in
      malignant ones. There is a significant positive correlation between SSTR2 mRNA
      and ER and PR expressions. Combined antiestrogen and somatostatin analogue in
      treatment of ER-positive breast cancers should be further investigated.

PMID- 14687473
TI  - 4-1BB gene expression in peripheral blood mononuclear cells from orthotopic liver
      transplant recipients with graft acceptance.
AB  - OBJECTIVE: To investigate the gene expression of 4-1BB in peripheral blood
      mononuclear cells (PBMCs) and the possible significance of the 4-1BB pathway
      after clinical orthotopic liver transplantation (OLT). METHODS: 4-1BB mRNA levels
      in PBMCs from 22 OLT patients were analyzed by RT-PCR. 4-1BB protein expressed on
      the surface of CD(4)(+) and CD(8)(+) T cells were detected by flow cytometry, and
      visualized with direct immunofluorescence and confocal fluorescence microscopy.
      Patients with primary liver cancer (PLC) and healthy volunteers served as
      controls. Six cases of recently performed liver transplantation were also
      observed in this study. RESULTS: 4-1BB mRNA was detected in PBMCs from both liver
      transplant patients with long-term graft acceptance (22 cases) and from
      transplant patients on day 1 to day 3 post-transplantation (6 cases), but was not
      found in PBMCs from transplant patients on day 7 to day 30 post-transplantation
      (6 cases). 4-1BB mRNA was also not found in samples from 8 of the healthy
      controls and 7 of the PLC patients, though very low expression was detected in
      the other 4 healthy volunteers and 6 PLC patients. Simultaneously, 4-1BB protein
      was expressed at nearly undetectable levels on CD(4)(+) and CD(8)(+) T cells from
      healthy controls, PLC patients, as well as OLT patients within the first month
      post-transplantation (6 cases). However, 4-1BB expression was found on the
      surface of CD(4)(+) and CD(8)(+) T cells from liver transplant patients with long
      term graft acceptance. Direct immunofluorescent staining and confocal
      fluorescence microscopy clearly revealed evidence of 4-1BB protein on cell
      membranes of CD(4)(+) and CD(8)(+) T cells from liver transplant patients with
      long-term graft acceptance. Simultaneously, a significantly higher percentage of
      CD(3)(+) CD(25)(+) T cells were found in liver transplant patients with long-term
      graft acceptance group as compared with the healthy control group (P < 0.05). The
      expression of 4-1BB protein on T cells did not correlate with the survival time
      of OLT patients postoperation. CONCLUSIONS: This study demonstrates that although
      patients remain in stable condition after liver transplantation under the
      treatment of immunosuppressants, activated T cells are present to some extent and
      4-1BB protein may be involved in this process. Effector T-cells can exert
      permanent immunoresponses against grafts under these circumstances. Therefore, we
      conclude that a new immune response balance is established under the combination
      of both treatment with immunosuppressants and natural immune responses against
      alloantigens. Manipulation of the 4-1BB/4-1BBL pathway may provide a therapeutic
      technique for prolonging graft survival.

PMID- 14687474
TI  - Bladder cancer therapy using combined proliferating cell nuclear antigen
      antisense oligonucleotides and recombinant adenovirus p53.
AB  - OBJECTIVE: To evaluate the antitumor efficacy of proliferating cell nuclear
      antigen antisense oligonucleotide (PCNA-ASO) in combination with recombinant
      adenovirus p53 (Ad-p53) against bladder cancer EJ and BIU-87 cells in vitro and
      in vivo. METHODS: Cells were transfected with Ad-p53 (100 MOI), and PCNA-ASO (1.6
      micro mol/L) was then introduced into the cells using a cationic lipid
      (lipofectamine, 20 micro l/ml). In vitro and in vivo antitumor effects of
      combining PCNA-ASO with Ad-p53 were measured using the MTT assay, flow cytometry,
      clone formation, and a nude mice model. RESULTS: The combination of PCNA-ASO and
      Ad-p53 inhibited cell viability in both the EJ (89.3%) and BIU-87 (78.6%) cell
      lines. The ability of the cells to form foci was also reduced by 74.8% in EJ
      cells and by 67.5% in BIU-87 cells (P < 0.01). A significant decrease of cells in
      the S phase (11.4% in EJ cells, 14.6% in BIU-87 cells) and a significant increase
      of cells in G1 phase (62.2% in EJ, 56.8% in BIU-87) were noted. The mean tumor
      volume after 7 days of treatment with PCNA-ASO or Ad-p53 in combination decreased
      to 47.6% or 36.4% of the initial tumor size in the two cell lines respectively.
      CONCLUSION: These results indicate that combined PCNA-ASO and Ad-p53 in the
      treatment of bladder cancer with mutant p53 has important therapeutic potential,
      significantly suppressing the growth of human bladder cancer both in vitro and in
      vivo.

PMID- 14687475
TI  - Effects of acupoints TENS on heat pain threshold in normal subjects.
AB  - OBJECTIVE: To delineate the influence of transcutaneous electrical nerve
      stimulation (TENS) on heat pain threshold and vibration threshold in human.
      METHODS: Twenty healthy, young subjects, aged from 20 to 39, participated in the
      study. They were randomly allocated into either TENS or placebo group. Thirty
      minutes of conventional TENS (200 micro s pulses at 100 Hz and 2 - 3 times
      sensory threshold) or placebo stimulation was applied to the acupuncture points
      (LI4) on each subject's left hand. Heat pain and vibration thresholds were
      measured using Medoc TSA-2001 and VSA-3000 respectively on the thenar eminence of
      each subject's left hand. These assessments were done at 30, 20 and 10 minutes
      before and 0, 10, 20, 30, 40 and 50 minutes after 30 minutes of TENS or placebo
      treatment. RESULTS: This study showed a significant increase in heat pain
      threshold by 0.81 degrees C and 1.54 degrees C respectively at 0 (P = 0.002) and
      20 minutes (P = 0.004) after 30 minutes of TENS application to the LI4 acupoint
      of young healthy subjects, compared with placebo stimulation. Interestingly, no
      significant difference in vibration threshold was found between the TENS and
      placebo groups. CONCLUSION: The effect of TENS on the acupoint is to reduce pain
      but not tactile (specifically vibration) sensibility.

PMID- 14687476
TI  - Experimental inhibition of corneal neovascularization by endostatin gene
      transfection in vivo.
AB  - OBJECTIVE: To investigate endostatin gene therapy of rat corneal
      neovascularization induced by acid cauterization. METHODS: pBlast-hEndostatin and
      pBlast-Mcs were identified by digestion with Nhe Iand Sal I, by PCR reaction, by
      sequence, and then by alignment of PCR products with the gene Bank using
      NCBIBLAST software. They were then purified with QIAGEN Endofree plasmid maxi
      kit. Rat corneal neovascularization models were made with 75% AgNO(3) and 25%
      KNO(3) cauterization. The treatment method was subconjunctive injection of the
      pBlast-hEndostatin with the control of pBlast-Mcs. RESULTS: pBlast-hEndostatin
      was found to contain the human endostatin gene. The rat corneal
      neovascularization induced by acid cauterization was significantly suppressed
      after subconjunctive injection of the pBlast-hEndostatin with inhibition rates of
      37%, 40.2%, and 42.8% respectively on the sixth, tenth, and fifteenth day. The
      inhibition rate for the density of corneal neovascularization was 40%. However,
      no inhibition effect on the length of the neovascularization and corneal
      inflammatory cells was observed. Corneal neovascularization areas were positively
      correlated with edema and corneal opacity. CONCLUSIONS: The plasmid of pBlast
      hEndostatin contained the human endostatin gene. The rat corneal
      neovascularization induced by acid cauterization can be partially inhibited by
      subconjunctive injection of the pBlast-hEndostatin mediated by liposomes.
      Endostatin produced by transfected fibroblast cells directly inhibits corneal
      neovascularization. This is not caused by inflammatory reaction inhibition.

PMID- 14687477
TI  - The association analysis of FcepsilonRIbeta with allergic asthma in a Chinese
      population.
AB  - OBJECTIVE: To investigate the link between the polymorphism of -109 and Glu237 in
      the high-affinity IgE receptor beta (FcepsilonRIbeta) gene and susceptibility to
      allergic asthma in a Chinese population. METHOD: Blood samples from 216 allergic
      asthma patients and 198 age- and sex-matched controls were studied. A -109C/T and
      a coding variant Glu237Gly in FcepsilonRIbeta were detected with polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The
      genotype frequencies were 0.403 for -109T/T, 0.491 for -109T/C and 0.106 for 
      109C/C in allergic asthma in a Chinese population. No significant difference in
      the distribution of -109C/T polymorphism was found between allergic asthma
      subjects and healthy controls, however, homozygosity for the -109T allele was
      associated with increased total plasma IgE levels in subjects with allergic
      asthma (F = 4.020, P < 0.05). The allele frequency of Gly237 in the patients and
      control was 0.236 and 0.136 respectively. There was a significant association
      between the Gly/Gly genotype and allergic asthma. Among allergic asthma patients
      Gly237 was significantly associated with high IgE levels. CONCLUSIONS: These
      results suggest that the Gly237 variant of the FcepsilonRIbeta gene is involved
      in the development of allergic asthma. The -109C/T and Glu237Gly polymorphisms
      are two of the genetic factor identified thus far, which affect total plasma IgE
      levels of allergic asthma patients in a Chinese population.

PMID- 14687478
TI  - Characterization and evaluation of a novel anti-MUC-1 monoclonal antibody:
      induction of the idiotypic network in experimental mice.
AB  - OBJECTIVE: To investigate the anti-idiotypic effect induced by a monoclonal
      antibody. METHODS: A conventional fusion method was used to obtain hybridoma
      cells producing monoclonal antibody, which were detected by flow cytometry. ELISA
      were used to detect the humoral response induced by the antibody in mice.
      Cytotoxic and proliferation experiments were used to detect the cellular response
      induced by the antibody in mice. RESULTS: CS20 is a MUC-1 specific monoclonal
      antibody that strongly reacts with MUC-1 antigen expressed on the cell surface of
      breast cancer cells. The antibody could not kill tumor cells directly through
      complement-dependent cytotoxicity or antibody-dependent cell-mediated
      cytotoxicity. However, after 6 administrations of mAb CS20-KLH (keyhole limpet
      hemocyanin) conjugated to BALB/c mice (n = 5) at a dose of 50 micro g/mouse, anti
      idiotypic antibodies and anti-anti-idiotypic antibodies were induced. T cells
      derived from CS20-KLH-immunized mice responded to mAb CS20, indicating the
      existence of idiotype-specific T cells. CONCLUSION: These data indicated the
      possibility of using MUC-1 specific antibody for active immunotherapy of breast
      cancer.

PMID- 14687479
TI  - Alterations of beta-catenin and Tcf-4 instead of GSK-3beta contribute to
      activation of Wnt pathway in hepatocellular carcinoma.
AB  - OBJECTIVE: The goal of this study is to investigate the inappropriate activation
      of Wnt pathway in the hepatocarcinogenesis. METHODS: We analyzed the alterations
      of three key components of Wnt pathway, beta-catenin, glycogen synthase kinase
      3beta (GSK-3beta) and T cell factor 4 (Tcf-4), in 34 samples of hepatocellular
      carcinoma (HCC) and paracancerous normal liver by immunohistochemistry,
      polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP),
      direct sequencing, semi-quantitative reverse transcription-polymerase chain
      reaction (RT-PCR) and in situ hybridization. RESULTS: We found 61.8% (21/34) of
      all the HCCs examined showed an abnormal beta-catenin protein accumulation in the
      cytoplasm or nuclei. RT-PCR-SSCP and direct sequencing showed that beta-catenin
      exon 3 mutations existed in 44.1% (15/34) of the HCCs. No mutations of GSK-3beta
      or Tcf-4 were detected in HCCs. Moreover, mRNA of beta-catenin and Tcf-4 but not
      GSK-3beta was found to be over expressed in HCCs. On analyzing the relationship
      between alterations of beta-catenin or Tcf-4 and C-myc or Cyclin D1 expression,
      we found that the mutations of beta-catenin as well as over expression of beta
      catenin or Tcf-4 gene were independently correlated with C-myc gene over
      expression in HCCs. CONCLUSIONS: Our present findings strongly suggest mutations
      of beta-catenin as well as over expression of beta-catenin and Tcf-4 gene
      activate the Wnt pathway in HCC independently with the target gene most likely to
      be C-myc.

PMID- 14687480
TI  - Hepatic differentiation from embryonic stem cells in vitro.
AB  - OBJECTIVE: To investigate an method for hepatic differentiation from embryonic
      stem cells (ES cells) in vitro and the resulting differentiation ratio, in order
      to develop a procedure for producing a new type of hepatocyte for hepatocyte
      replacement therapy in the treatment of liver failure. METHODS: ES cells from
      Balb/C mice were cultured and maintained in an undifferentiated state in gelatin
      coated dishes using Dulbecco's modified Eagle's medium (DMEM) containing 1000
      U/ml leukemia inhibitory factor (LIF). Then, LIF was withdrawn from the DMEM to
      allow the ES cells to develop into embryonic bodies (EBs). EBs were plated onto
      tissue culture dishes, and growth factors such as acidicfibroblast growth factor
      (aFGF) and hepatocyte growth factor (HGF) were added to the medium to promote
      directional differentiation. The course of development and differentiation was
      observed dynamically using an inversion microscope. The expression of hepatic
      proteins, such as alpha-fetoprotein (AFP), albumin (ALB), cytokeratin 8 (CK8),
      cytokeratin 18 (CK18), in cytoplasm was analyzed by immunocytochemistry (ICC).
      The concentration of ALB in the medium was determined dynamically by
      radioimmunoassay (RIA). RESULTS: ES cells replicated as clones, without
      differentiating, in DMEM containing LIF. They developed into EBs in medium
      without LIF. Our ICC assay showed that differentiating cells did not express
      hepatic proteins, such as AFP, ALB, CK8, and CK18 until day 7, day 9, day 11, and
      day 11, respectively (up to 2 days later when growth factors are not present).
      The concentration of AFP in the medium was first detected on day 8, at a
      concentration of 3.4 ng/ml, and increased to 22.8 ng/ml by day 15. The
      concentration of ALB in the medium was 0.2 micro g/ml on day 11, and increased to
      2.2 micro g/ml by day 15. ALB-positive cells under ICC manifest morphological
      structures were consistent with normal mouse hepatocytes. The differentiation
      ratio of hepatocytes in the ES cell differentiation system was 30% on day 15
      (significantly lower without the presence of growth factors). CONCLUSIONS: ES
      cells can differentiate into mature hepatocytes. Growth factors, such as aFGF and
      HGF, can enhance this differentiation and produce sufficient numbers of
      functional hepatocytes. This method may be a reliable new way of differentiating
      ES cells into hepatocytes for use in replacement therapy in the treatment of
      liver failure.

PMID- 14687481
TI  - Inhibitory effects of recombinant neurotoxin BmK IM on seizures induced by
      pentylenetetrazol in Rats.
AB  - OBJECTIVE: To elucidate the inhibitory effects of recombinant Chinese scorpion
      neurotoxin BmK IM on seizures induced by pentylenetetrazol (PTZ) and the possible
      mechanism. METHODS: After purifying recombinant BmK IM from an E. coli cell line,
      its toxicity (both LD50 and minimum lethal dose) on rats was determined. BmK IM
      was then microinjected into the CA3 region of the right hippocampus and its
      ability to inhibit the effects of an intraperitoneal injection of PTZ was
      assessed. The effects of BmK IM on the electrophysiological properties of
      isolated CA3 pyramidal neurons were then studied using whole-cell patch clamp
      techniques. RESULTS: BmK IM can significantly prolong the latent period of
      epileptic seizures, decrease the degree of seizures, and decrease the frequency
      of epileptiform discharges induced by PTZ. At the same time, 24h after injection
      of BmK IM into the hippocampal tissue, BmK IM significantly reduces the
      concentration of the neurotransmitter glutamate and alleviates PTZ-induced
      lesions in the hippocampus. Whole-cell patch clamp recordings indicate that BmK
      IM inhibits INa of rat hippocampal neurons in a dose-dependent manner. BmK IM
      significantly shifts the activation curve of INa in a positive direction,
      indicating that BmK IM enhances the threshold potential of INa. CONCLUSIONS: BmK
      IM has significant anti-epileptic properties, and may prove useful as a drug in
      the therapy of epilepsy. The inhibitory effects of BmK IM on seizures caused by
      pentylenetetrazol might depend on reductions in the release of presynaptic
      glutamate via the blocking of Na+ channels.

PMID- 14687482
TI  - Detection of specific IgE antibodies to major and minor antigenic determinants in
      sera of penicillin allergic patients.
AB  - OBJECTIVE: To investigate the mechanism(s) of penicillins allergic reaction.
      METHODS: The radioallergosorbent test (RAST) was used to detect 9 specific IgE
      antibodies, including major antigenic determinants: benzylpenicilloyl (BPO),
      ampicilloyl (APO), amoxicilloyl (AXO), phenoxomethylpenicilloyl (PVO) and
      flucloxacilloyl (FLUO), and minor antigenic determinants: benzylpenicillanyl
      (BPA), amoxicillanyl (AXA), 6-aminopenicillanic (APA) and
      phenoxomethylpenicillany (PVA), in the sera of 32 penicillin allergic patients.
      The relationship between specific IgE antibodies and penicillins chemical
      structures was studied by radioallergosorbent inhibition test. RESULTS: Nineteen
      of 32 patients (59.4%) were RAST positive, among whom, five cases were positive
      only to one or two antigenic minor determinants, and three cases were positive
      only to one or three major antigenic determinants. The remaining 11 patients were
      positive not only to major antigenic determinants but also minor antigenic
      determinants. In 9 specific IgE antibodies, the positive rate of PVA-IgE was the
      highest (34.38%), followed by BPO-IgE (31.25%). The positive rate of FLUO-IgE was
      the lowest (15.63%). Of the total patient group, 53.13% were positive to one or
      more minor antigenic determinants, while 37.5% (12/32) were positive to one or
      more major antigenic determinants. The percentage of patients with urticarial
      reactions who were positive to minor antigenic determinants (63.16%) was
      significantly higher than observed in the anaphylactic shock group (38.5%, P <
      0.05). CONCLUSIONS: The minor antigenic determinant was important in allergic
      reaction. The combining sites of the specific IgE antibodies were likely to be
      the side-chain of drug or the overwhelming drug molecule.

PMID- 14687483
TI  - Effects of nimodipine and fructose-1,6-diphosphate on cerebral damage in carbon
      monoxide poisoning mice.
AB  - OBJECTIVE: To study the dose- and time-dependent protective effects and the
      synergistic effects of nimodipine (NMDP) and fructose-1,6-diphosphate (FDP)
      against cerebral damage induced by acute carbon monoxide (CO) poisoning in mice.
      METHODS: Male mice were exposed to CO 170 mL/kg, i.p. After CO intraperitonealy
      exposure, mortality of mice, change in memory function estimated by passive
      avoidance test, the pathomorphologic observation of brain tissue slices, as well
      as changes of activities of monoamine oxidase (MAO)-B and Ca(2+)-Mg(2+)-ATPase in
      cerebral tissue were studied. In dose-dependent protective effect study, NMDP
      (10.6, 5.3, 2.7 mg/kg) and FDP (2.6, 1.3, 0.67 g/kg) was injected ip,
      respectively 15 min after CO exposure. To study the time-effect relationship of
      drugs, NMDP (5.3 mg/kg) and FDP (1.3 g/kg) were administered ip respectively 15
      minutes, 45 minutes and 120 minutes after CO exposure. The combination of NMDP
      (2.7 mg/kg) and FDP (0.67 g/kg) was administered ip15 minutes, 45 min and 120
      minutes after CO exposure to study the synergism of the two drugs. RESULTS:
      Either NMDP (10.6, 5.3 mg/kg) or FDP (2.6, 1.3 g/kg) administered ip within 15
      minutes after CO exposure significantly decreased the impairment of memory
      function and mortality rate induced by CO, inhibited the decrease of Ca(2+)
      Mg(2+)-ATPase activity, blunted the rising of MAO-B activity and prevented the
      delayed hippocampal neuronal death in poisoning mice. To our surprise, the
      combined use of NMDP (2.7 mg/kg) and FDP (0.67 g/kg) within 15 minutes after CO
      exposure had similar effects to that in NMDP (10.6, 5.3 mg/kg) and FDP (2.6, 1.3
      g/kg). CONCLUSIONS: These results suggest that the impairment of CO on brain can
      be attenuated if NMDP or FDP are administered sufficiently and quickly as soon as
      possible after CO exposure and there exists a synergism of FDP and NMDP against
      CO poisoning damage.

PMID- 14687484
TI  - The expression of insulin-like growth factor-I mRNA and polypeptide in rat
      osteoblasts with exposure to parathyroid hormone.
AB  - OBJECTIVE: To investigate the insulin-like growth factor-I (IGF-I) gene and
      polypeptide expression in cultured rat osteoblast (ROB) and the role of IGF-I in
      mediating the cell-to-cell communication by mimicking the pharmacokinetics of
      parathyroid hormone (PTH). METHODS: The ROB was cultured with three kinds of
      treatment: (1) Control (Ctr), the cells were cultured without PTH during the
      first 6 hours and the subsequent 42 hours in a 48-hour cycle; (2) Intermittent
      exposure to PTH (Itm), the cells were cultured with PTH during the first 6 hours,
      but without PTH in the subsequent 42 hours; and (3) Continuous exposure to PTH
      (Ctu), the cells were cultured with PTH during the first 6 hours and the
      subsequent 42 hours. RESULTS: The bone-forming activities of ROB were increased
      in Itm and inhibited in Ctu. The IGF-I mRNA content in Itm cells was elevated
      only during the first 6 hours and that in Ctu cells was elevated at any time
      during an incubation cycle. The free IGF-I concentration in the medium of Itm
      cells was generally higher and that of the Ctu cells was generally lower compared
      with those of the Ctr cells. The IGF-I antibody significantly reduced the
      alkaline phosphatase activity within the cells of Ctr and Itm. CONCLUSIONS: PTH
      rapidly and constantly stimulates the IGF-I gene transcription of osteoblast.
      There was an obvious discrepancy between the IGF-I mRNA content within the
      osteoblast and the free IGF-I level around the osteoblast in either mode of PTH
      action. The IGF-I might be important for osteoblast-osteoblast communication and
      bone-forming activity, not only in intermittent PTH administration, but also in
      the physiological functioning of osteoblasts.

PMID- 14687485
TI  - Sensitivity and specificity of different staining methods to monitor apoptosis
      induced by oxidative stress in adherent cells.
AB  - OBJECTIVE: To study the sensitivity and specificity of different staining methods
      to monitor apoptosis induced by oxidative stress in adherent cells. METHODS:
      Sensitivity and specificity of several common methods for apoptosis determination
      were evaluated (Apo2.7-expression, Annexin V-binding, TUNEL-reaction, poly-(ADP
      ribose)-polymerase-(PARP) cleavage and single-stranded-DNA (ssDNA) staining).
      Apoptosis was induced by oxidative stress generated by hydrogen peroxide in 3
      cultured cells types growing as adherent monolayer (MiaPaCa-2, Hep-G2 and human
      skin fibroblasts), necrosis was induced by depletion of cellular ATP using sodium
      azide. Cells positively stained by the respective apoptosis assay were quantified
      and alterations of cell morphology were monitored by fluorescence microscopy. The
      date was analyzed by one-way analysis of variance and significance test of
      correlation coefficient. RESULTS: One hour after apoptosis induction significant
      cell fractions were positively stained for ssDNA (33% with MiaPaCa-2 cells, 35%
      with Hep-G2 cells, 56% with human skin fibroblasts). PARP-cleavage was less
      sensitive compared to the ssDNA-staining. Apo2.7-expression, Annexin V-binding
      and TUNEL-reaction were not applicable to detect early apoptosis induced by
      oxidative stress (below 2 hours), but were efficiently monitoring late apoptosis.
      Specificity of ssDNA-staining was complete with each cell type even 4 hs after
      induction of necrosis by the highest sodium azide concentration. In contrast, the
      same experimental conditions resulted in 50% - 90% positively stained necrotic
      cells by using Apo2.7-expression, TUNEL-reaction or Annexin V-binding.
      Surprisingly, specificity of PARP-cleavage was highly depending on the respective
      cell type. CONCLUSIONS: Our study prove that among the five methods investigated
      only ssDNA-staining allowed to completely differentiate apoptosis from necrosis,
      and is thus suitable to reliably detect early as well as late apoptosis.
      Therefore, the ssDNA-staining may be used as reference method to clearly identify
      apoptosis induced by oxidative stress in adherent cells. The TUNEL-reaction,
      annexin-V-binding and Apo-2.7-expression may be used to quantify the number of
      apoptotic and necrotic cells especially at later stages but without
      discrimination of apoptosis and primary or secondary necrosis.

PMID- 14687486
TI  - Treatment of symptomatic epilepsy with lesionectomies combined with bipolar
      coagulation of the surrounding cortex.
AB  - OBJECTIVE: To observe the clinical effects of lesionectomies combined with
      bipolar coagulation of the surrounding cortex (BCSC) on symptomatic epilepsy.
      METHODS: The effectiveness of lesionectomies combined with BCSC (71 patients) and
      of lesionectomies alone (78 patients) were compared in follow-up surveys
      conducted 2 - 5 years (average of 37 months) post-operation. RESULTS: Treatment
      in the BCSC group was significantly more effective than in the lesionectomy group
      (P < 0.01). Meanwhile, patients in the BCSC group suffered no permanent post
      operative complications. CONCLUSION: Lesionectomy combined with BCSC is a new,
      effective and safe treatment for symptomatic epilepsy.

PMID- 14687487
TI  - Association between fasting and postprandial triglyceride levels and carotid
      intima-media thickness in type 2 diabetes patients.
AB  - OBJECTIVE: To investigate the association of fasting and postpiandial
      triglyceride with carotid intima-media thickness among type 2 diabetic patients
      in southeast China. METHODS: A total of 78 type 2 diabetic patients from
      southeast China were recruited. All the subjects underwent a standardized mixed
      meal test (SMMT) and an oral glucose tolerance test. Carotid intima-media
      thickness (IMT) was measured by color doppler ultrasound examination. RESULTS:
      Postprandial triglyceride (PTG) after SMMT increased significantly in type 2
      diabetic patients. The carotid IMT in patients with postprandial
      hypertriglyceridemia was significantly greater than that in patients with
      postprandial normal-triglyceridemia (0.90 mm vs 0.81 mm, P < 0.05), which
      remained significant after adjustment for fasting TG and HDL-c levels, and the
      IMT in patients with fasting hypertriglyceridemia only had tendency to increase
      compared to patients with fasting normal-triglyceridemia (0.87 mm vs 0.84 mm, P >
      0.05). CONCLUSION: The results suggest that postprandial hypertriglyceridemia may
      be an independent risk factor of early atherosclerosis in type 2 diabetes.

PMID- 14687488
TI  - Expression of hypoxia-inducible factor 1alpha in human normal, benign, and
      malignant prostate tissue.
AB  - OBJECTIVE: To investigate hypoxia-inducible factor 1alpha (HIF-1alpha) protein
      expression in normal prostates (NP), benign prostatic glandular hyperplasia
      (BPH), and prostate adenocarcinoma (Pca). METHODS: HIF-1alpha protein expression
      was determined by immunohistochemistry in formalin-fixed and paraffin-embedded
      specimens obtained from 13 cases of NP, 28 cases of BPH, and 34 cases of Pca. In
      cases of Pca, the relationship between HIF-1alpha protein expression and certain
      clinicopathological factors, such as clinicopathologic stage and Gleason score,
      was evaluated. RESULTS: NP manifested no immunoreactivity, whereas Pca and BPH
      showed significantly increased HIF-1alpha protein expression. A significantly
      higher expression was observed in Pca specimens compared with BPH samples. In
      Pca, no significant relationship between HIF-1alpha protein expression and
      clinicopathological factors was found. CONCLUSION: Our findings of increased HIF
      1alpha protein expression in BPH and Pca specimens suggests the potential role of
      this protein in BPH and Pca.

PMID- 14687489
TI  - Study of the relationship between the onset of peptic ulcers and meteorological
      factors.
AB  - OBJECTIVE: To discuss the relationship between the onset of peptic ulcers (PU)
      and meteorological factors (MF). METHODS: In reviewing records from 17 hospitals
      in the city of Nanning from 1992 to 1997, we found 24, 252 cases of PU in 104,
      121 samples of gastroscopic examinations. We then calculated the detectable rate
      of PU (DRPU) during each season every five days (FD) and made a correlated
      analysis with the seasonal MF during the same period in Nanning. Finally, we made
      a multiple regressive correlated analysis of DRPU and the 5MF for the same period
      of the year. A forecast model based on the MF of the previous FD was established.
      The real value and the forecast value was being tested and verified. RESULTS:
      From 1992 to 1997, the DRPU is: winter and spring > summer and autumn (P <
      0.005). There is a close relationship between the DRPU and the average
      temperature (AT), the average highest temperature (AHT), the average lowest
      temperature (ALT), average air pressure (AAP) and the average dew point
      temperature (ADT) of the five days of the same period of the year (the correlated
      coefficients are -0.5348, -05167, -0.5384, 0.4579 and -0.4936, respectively),
      with P < 0.01. The AT, AHT, ALT, AAP and ADT of the previous FD are of great
      value in forecasting the onset of PU, with its real value and forecast value
      corresponding to 66.6%. CONCLUSIONS: There exists a close relationship between
      DRPU and the AT, AHT, ALT, AAP and ADT of the FD for the same period. A mid-term
      medical meteorological forecast of the onset of PU can be made more accurately
      and reliably according to the close relation between the DRPU and some MF of the
      previous FD.

PMID- 14687490
TI  - Orthotopic ileal neobladder similar to original bladder.
AB  - OBJECTIVE: To report the surgical techniques and results of an 8-year follow-up
      study of 42 patients with a modified orthotopic ileal neobladder restoring normal
      anatomical relationship. METHODS: Total cystoprostatectomy was performed
      extraperitoneally. A 45 - 50 cm segment of the ileal loop was isolated,
      detubularized, and reconfigured into an "M"-shape to form a pouch. Bilateral
      ureters were implanted by inserting 1 cm distal segment into the pouch. The
      bottom of pouch was opened and anastomosed with the urethra. RESULTS: Forty-two
      patients were followed up for 6 to 96 months,90.5% of whom were continent in the
      daytime, and 85.7% at night. Two patients had a difficulty in urination. The
      average volume of the pouch was (361 +/- 48) ml at 12 months postoperation.
      Urodynamic examination showed the average peak voiding pressure was (86.8 +/-
      21.4) cm H(2)O. The average maximum flow rate (Qmax) was (18.4 +/- 6.1) ml/s. No
      remarkable ureter reflux and obstruction were found. No patient was detected to
      have urethral carcinoma. CONCLUSIONS: Extraperitoneal cystectomy can avoid the
      tumor contamination of the abdomen and intestinal interference of the operative
      field. The ureter-inserting implantation technique is a simple anti-reflux
      anastomosis method with less ureter stenosis rate. Isolating the neobladder and
      ureters from the peritoneal cavity can reduce the postoperative complications,
      such as adhesive ileus, internal hernia, and urine leakage into the peritoneal
      cavity. The neobladder is similar to the original bladder in position, volume,
      shape and anti-reflux ureter connection.

PMID- 14687491
TI  - Comprehensive treatment of complicated plantar ulcers in leprosy.
AB  - OBJECTIVE: To investigate feasible treatment methods for plantar ulcers in
      leprosy patients according to the agreement between the Ministry of Health (MOH)
      of China and the Leprosy Mission International (LMI). METHODS: A total of 2599
      complicated foot ulcers in 1804 leprosy cases underwent surgic treatment. Plastic
      fixation and supports were used, dressings were changed regularly, and protective
      footwear and modified insoles were provided. RESULTS: Of the 2599 foot ulcers
      1446 (55.64%) healed. The cure rate of the patients treated in leprosy hospitals
      was 71.31%, with 219 (15.15%) recurrences of foot ulcers. The recurrence rate of
      those who lived at home was 18.35%. CONCLUSIONS: Comprehensive treatment of foot
      ulcers has a high cure rate and a low recurrence rate. Reduction of workload,
      avoidance of long distance walking, intensification of education on foot self
      care and provision of financial support are the main measures for preventing a
      recurrence of foot ulcers.

PMID- 14687492
TI  - [Study on the epidemiology and distribution of human immunodeficiency virus-1 and
      hepatitis C virus infection among intravenous drug users and illegal blood donors
      in China].
AB  - OBJECTIVE: To determine the epidemiologic features and distribution of human
      immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) infection among
      intravenous drug users and illegal blood donors in China. METHODS: Polymerase
      chain reaction (PCR) amplification and DNA sequencing were used to evaluate the
      HIV-1 gag p17 and env C2-V3 regions, as well as the HCV 5'NCR and E1/E2 regions.
      RESULTS: Among 239 subjects with reported HIV-1 infection, 56.9% (136/239) were
      seropositive for anti-HCV. Of those, 96.3% (131/136) were co-infected with HCV
      through intravenous drug use and illegal blood donation. Intravenous drug users
      in Yunnan, Guangxi and Xinjiang provinces were infected with HIV-1 subtype C and
      HCV genotypes 1b, 3a, 3b and 4, whereas illegal blood donors in Henan province
      harbored HIV-1 subtype B' and HCV genotypes 1b and 2a. Five different HIV-1
      subtypes were identified among 17 HIV-1-infected individuals from Beijing.
      CONCLUSIONS: Multiple HIV-1 subtypes and HCV genotypes were identified in China
      which were associated with several different modes of transmission. Homogeneity
      within the sequences of the two viruses suggested the recent, but separate,
      outbreaks of HIV-1 and HCV infection. The distinct distribution patterns of HIV-1
      and HCV genotypes in two high-risk groups seemed to be more closely linked to the
      mode of transmission than to geographic proximity.

PMID- 14687493
TI  - [Study on the evolutionary pressure on the env gene of the human immunodeficiency
      virus type 1 CRF01-AE strains circulating in China].
AB  - OBJECTIVE: To identify variations in the env gene of human immunodeficiency virus
      type 1 (HIV-1) subtype CRF01-AE strains circulating in China and to elucidate the
      potential relationship between genetic variation and evolutionary pressure.
      METHODS: Fragments of the HIV-1 env gene were amplified by nested-polymerase
      chain reaction (n-PCR) from the whole blood of HIV-1 infected individuals from
      four provinces in Southeast China (Guangdong, Hunan, Jiangsu and Jiangxi). The
      PCR products were then directly sequenced by ABI 377 DNA sequencers. The
      sequences covering the env V3-V4 region of 34 HIV-1 subtype CRF01-AE strains were
      selected to analyse phylogenetic trees and amino acid mutations. The accumulation
      of synonymous (Ks) and antonymous (Ka) substitutions as well as Ks/Ka ratios were
      calculated using DIVERGE. RESULTS: Phylogenetic trees showed that the 34 HIV-1
      subtype CRF01-AE strains from China clustered with the Chinese AE reference
      strain (AE.97CNGX2F), as well as with the reference strains from Thailand
      (AE.CM240 and AE.93TH253). The amino acid sequences of the env V4 and C3 regions
      in the samples were highly variable, compared with those of V3 and V3-downstream
      regions. The V3 loop central motif in the majority (87.5%) of the strains was
      GPGQ. The majority of strains did not contain positively charged amino acids at
      positions 306 and 320 in V3 loop. The N-linked glycosylation sites in the V3-V4
      region and flanking regions in these strains were relatively conserved. Analysis
      of the entire region showed that the mean Ks values were significantly higher
      than that of the Ka values (P < 0.001), with the Ks/Ka significantly higher than
      1.0 (P < 0.001). In contrast, the Ks/Ka ratio in the V4 region was significantly
      lower than 1.0 (P < 0.01). CONCLUSIONS: Our study indicated that the majority of
      HIV-1 subtype CRF01-AE strains circulating in China were highly homogeneous. The
      amino acid sequences of the V4 and C3 regions were significantly more variable
      than those of the V3 loop. Our analysis also suggested that the phenotype of
      nearly all strains was likely to be non-syncytium inducing (NSI). Finally, the
      variation found in the V3-V4 sequence was significantly influenced by functional
      constraints as opposed to positive selective pressure, while the variability of
      the lone V4 region was strongly related to positive selective pressure.

PMID- 14687494
TI  - [Preliminary study on the association of chemokine RANTES gene polymorphisms with
      HIV-1 infection in Chinese Han population].
AB  - OBJECTIVE: To detect the single nucleotide polymorphism (SNP) of chemokine
      regulated upon activation, normal T cell expressed and secreted (RANTES) promoter
      and first intron of asymptomatic, human immunodeficiency virus 1 (HIV-1) infected
      individuals of in Han Chinese and evaluate the influence on HIV-1 infection by
      variants. METHODS: Case-control study was adopted, Genotypes of RANTES promoter 
      403 and -28 from 538 samples and RANTES first intron In1.1 from 300 samples of
      Han Chinese were detected by DNA sequencing or by polymerase chain reaction
      restriction fragment length polymorphism. RESULTS: There were six genotypes of
      RANTES promoter -403 and -28 found in Han Chinese group. The distribution of
      genotypes was AC/AC 12.4%, AC/AG 3.5%, AC/GC 29.2%, AG/GC 10.9%, GC/GC 42.1%,
      AG/AG 1.5%. The haplotypes was GC 62.7%, AC 28.7%, AG 8.6%. Compared with AC/AC,
      Odd ratio (OR) of RANTES genotypes AC/AG, AC/GC, AG/GC, GC/GC was associated with
      weaker reduced susceptibility to HIV-1 infection. However, there were no
      significant contents of the allele frequencies between people living with HIV-1
      and healthy individuals. The distribution of RANTES In1.1 alleles were T/T 71.0%,
      C/T 19.9%, C/C 9.1% and haplotypes were RANTES In1.1T 81%, In1.1C 19%,
      respectively; There were significant differences of RANTES In1.1 between people
      with HIV-1 infection and healthy individuals in males. The In1.1C-bearing
      genotypes would increase susceptibility to HIV-1 infection but no significant
      differences in females were found. Strong linkage disequilibrium was observed
      between all of the three RANTES SNPs. CONCLUSION: The two -403A/G, -28C/G
      variants in RANTES promoter region and intron In1.1 T/C mutation genotype were
      found to be associated with the genetic susceptibility to HIV-1 infection among
      the Han Chinese. However, the In1.1C allele or its haplotypes in RANTES intron 1
      displayed a stronger dominant association with HIV-1 infection in males.

PMID- 14687495
TI  - [A molecular epidemiological study on the human immunodeficiency virus infection
      in Jiangsu province].
AB  - OBJECTIVE: To identify subtypes of human immunodeficiency virus 1 (HIV-1) strains
      and their distribution, infection sources, and the trends of HIV infection in
      Jiangsu province. METHODS: Anticongulated bloods from 46 infected persons were
      collected to separate previrus DNA. HIV-1 env genes were then amplified by nested
      PCR and sequenced for their C2-V3 region so as to identify subtypes. The analysis
      of consensus sequence, genetic distance and phylogenetic tree were conducted with
      GCG software. RESULTS: By the end of 2001, there had been six subtypes of HIV-1
      strains identified in Jiangsu province: A, B, B', C, D and E. The predominant
      subtypes were C (accounting for 40.48%) and B' (accounting for 38.10%). Subtype C
      accounted for 86.67% among injecting DUs while subtype B' accounted for 91.67%
      among commercial blood donors and receivers. CONCLUSION: Subtype B'among
      commercial blood donors was brought to Jiangsu from neighboring provinces. The
      outbreak of HIV-1 infection among local DUs was caused by subtype C from Xinjiang
      province. Findings from HIV/AIDS molecular epidemiologic study suggest that it is
      challenging for Jiangsu to treat patients, apply vaccine, prevent and control
      AIDS in the future.

PMID- 14687497
TI  - [A study on the estimation of the size of male homosexual population].
AB  - OBJECTIVE: To study the practical survey method on estimating the size of male
      homosexual population. METHODS: Nine male homosexual gathering spots were
      selected and three methods as division method, capture-mark-recapture method and
      multiplier method were applied in counting the numbers of homosexual men in one
      city in Sichuan province. RESULTS: Number of counting through division method was
      877 and the three numbers through capture-mark-recapture method were 1408, 1207
      and 949 respectively. However, appropriate data was not obtained by multiplier
      method. CONCLUSIONS: Division method was easy to operate with its high
      credibility, but costly. Capture-mark-recapture method was less costly less both
      in capital and time, and the results could be testified to each other. Multiplier
      method should be modified before applied to obtain reliable information.

PMID- 14687498
TI  - [Influenza surveillance program in 2002-2003, in China].
AB  - OBJECTIVE: To study the prevalence of influenza viruses from April 2002 to June
      2003. METHODS: Subtypes were identified by HI test, HA gene was amplified by RT
      PCR and the nucleotide sequences of HA gene were analyzed. RESULTS: During the
      period of April 2002 to June 2003, a total number of 16 135 throat swab specimens
      were collected in 23 provinces, metropolitan areas and municipalities with 1 113
      strains identified as influenza viruses positive, by the Chinese National
      Influenza Center. The rate of isolation was 6.9%. Of the 1 113 strains, 66
      strains were influenza A-H1N1, 544 strains were influenza A-H3N2 viruses while 98
      and 405 strains belonged to B/Yamagata and B/Victoria viruses with the rates of
      isolation on each subtype were 5.9%, 48.9%, 8.8% and 36.4%, respectively.
      Majority of influenza A (H3N2) viruses were isolated in the epidemic period of
      December 2002 and January 2003 as well as in the non-epidemic period. Different
      to influenza A-H3N2, most of the B/Victoria viruses were isolated in winter. The
      HA1 gene of B type strains belonged to B/Victoria lineage. Sequence analysis
      indicated that there were variations in influenza type in this epidemic season.
      CONCLUSIONS: Although influenza A subtype H1N1 and H3N2 as well as B type viruses
      were co-circulating in our country, the influenza A (H3N2) and B/Victoria
      isolates were found the predominant strains in the period of this study which
      were different from the previous years. The fact that the increase of proportion
      on B/Victoria and its widespread in many areas suggested there had been a change
      of epidemiological features caused by influenza viruses in China. It seemed
      important to pay more attention to the variation of HA gene in influenza A type
      (H3N2) strains.

PMID- 14687496
TI  - [Study on factors associated with heterosexual-transmission of human
      immunodeficiency virus in central China].
AB  - OBJECTIVE: To investigate the factors of the human immunodeficiency virus (HIV)
      associated with sexual-transmission in central China. METHODS: (1) Cross
      sectional study: couples that one was HIV positive were selected in Henan and
      Hebei province of China. The couples must be 20 - 50 years old with normal
      function on sexual intercourse. Cordant couples that subsequently infected
      partners were at risk of infection solely through sexual contact with the HIV
      seropositive partner and the discordant couples that the seronegative partners
      were at risk of infection solely through sexual contact with the HIV-seropositive
      partner, were selected. Plasma viral load, CD4 cell count were tested. (2) Case
      control study was used to compare 7 sexual transmitted cases and 56
      nontransmitted controls with respect to the frequency of sexual intercourse,
      plasma viral load and CD4 cell count. RESULTS: (1) A total of 87 couples that at
      least one partner was HIV positive were recruited include 56 discordant couples
      and 7 cordant couples with whom sexual transmission had happened. The rate of
      sexual transmission was 11.1% among those at the risk of sexual transmission. (2)
      Of the discordant couples, male positive rate 25%, female positive was 75%. (3)
      The risk for transmission was higher in those couples with the frequency of
      unprotected vaginal sexual intercourse (> or = 4 times per month) than the
      reference group (< 4 times per month) (Fisher's exact test, P = 0.047, OR = 8.0).
      Median plasma viral load was significantly higher in the antecedent infected
      partners of cordant couples than the positive partner of discordant couples
      (378,285.71 vs 136,578.57 copies/ml, t = 3.591, P < 0.01). The odds ratio was
      22.0 for plasma viral load > or = 100,000 copies/ml compared with the reference
      group of < 100 000 copies/ml (Fisher's exact test, P = 0.016). The CD4 cell count
      and CD4/CD8 of the transmitted group were significantly lower than that of the
      nontransmitted (t = 2.767, P < 0.05; t = 6.06, P < 0.05). CONCLUSIONS: The
      frequencies of heterosexual-transmission in central China were relatively low.
      The risk of heterosexual transmission was related to the frequency of sexual
      intercourse. Higher plasma viral load and lower CD4 count was strongly correlated
      with high risk of heterosexual transmission.

PMID- 14687499
TI  - [Evaluation on the functions and cost of 'fever clinics' during the period of
      severe acute respiratory syndrome epidemics in Beijing].
AB  - OBJECTIVE: To identify the experiences and lessons learned on 'fever clinics'
      during the severe acute respiratory syndrome (SARS) epidemic in Beijing and to
      propose a better model in monitoring SARS to fit the 'fever clinics' into current
      situation. METHODS: Both qualitative and quantitative methods were used in data
      collection and analyses. Quantitative surveys would include 1. The setting,
      functions and administration of current 63 'fever clinics' in Beijing; 2. Survey
      on patients with fever who had visited 'fever clinics' and randomly selected from
      the 63 fever clinics; 3. Survey on physicians working in the 'fever clinics'.
      Qualitative studies would include discussion or interview with administrators,
      physicians working in the 'fever clinics' and field studies on 23 randomly
      selected 'fever clinics' as well as telephone interview to the staff working in
      the hospitals that did not have the 'fever clinics'. RESULTS: A couple of
      significant problems raised during the study including: 1. Low coverage of
      current surveillance system. 89% of the hospitals were not covered by the
      surveillance system which reflecting the misjudgment on the patients with fever
      that they would only attend 'fever clinics' to seek for medical help. The fact
      was that most of the hospitals where 'fever clinics' had not been set also
      received patients with fever. 2. Information related to patients with fever needs
      to improve regarding its completeness and accuracy. 3. Significant unbalance in
      daily cost and effectiveness in most of the 'fever clinics' was noticed.
      CONCLUSION: 'Fever clinics' needs to be adjusted to meet the possible SARS
      epidemic in coming winter and spring. Short-term and long-term suggestions were
      proposed regarding SARS monitoring through the functions of 'fever clinics' in
      Beijing.

PMID- 14687500
TI  - [Genetic analysis of Yersinia pestis strains isolated in China].
AB  - OBJECTIVE: The strains of Yersinia pestis isolated in different period and
      different natural foci in China were analyzed. METHODS: Traditional and molecular
      biological methods were used. Rhamnose fermentation, rRNA gene copy number,
      nitrite reduction, and the glycerol fermentation were important characters for
      typing, and pulse field gel electrophoresis (PFGE) and random amplified
      polymorphic DNA (RAPD) profile could reflect the genetic distance between the
      strains. RESULTS: The strains could be divided into 15 genetic types by those 6
      characters with each of them covered an isolated geographical territories.
      CONCLUSION: The characters of strains were described; the genetic relationship of
      different types, their evolution, and the forming and shift of plague natural
      foci were analyzed.

PMID- 14687501
TI  - [Surveillance finding on rotavirus in Changchun children's hospital during July
      1998-June 2001].
AB  - OBJECTIVE: To establish baseline patterns of rotavirus diarrhea and to describe
      its epidemiologic features in Changchun city, prior to rotavirus vaccine
      immunization. METHODS: Hospital-based surveillance was conducted among children
      under 5 years old with acute diarrhea in Changchun Children's Hospital. Fecal
      samples were determined to identify rotavirus by PAGE and/or ELISA. G serotypes
      of rotavirus were identified by ELISA and/or nested RT-PCR. P genotyping were
      carried out by RT-PCR. All data were computerized and analysed by "Generic Manual
      on Rotavirus Surveillance" set by CDC in the USA. RESULTS: In total, 2 343
      diarrhea cases were screened and 1 211 fecal samples were collected. Rotavirus
      was detected in 31.0% among outpatients and 52.9% in inpatients. During the peak
      of the season (November through March), 58.6% of diarrhea was caused by rotavirus
      among inpatients. 95.0% of rotavirus diarrhea cases occurred among children aged
      < 2 years. The predominant strain was serotype G1 (82.4%), followed by G2 (5.0%),
      G3 (3.3%), G4 (0.9%). P genotyping showed that P[8] and P[4] were the most common
      ones. Nine different P-G combinations were identified, four strains (P[8]G1,
      P[4]G2, P[8]G3, and P[8]G4) commonly seen worldwide accounted for 75.6% of the
      total. Taken together with uncommon strains, including the novel types P[4]G4 and
      P[8]G2, it highlights the extraordinary diversity of rotaviruses circulating in
      China. CONCLUSION: Rotavirus is the major cause of severe child diarrhea in
      Changchun. Developing a rotavirus vaccine for prevention of severe disease and
      reduction of treatment costs seemed to be necessary.

PMID- 14687502
TI  - [The study on the 0, 12 month vaccination schedule' of Healive inactivated
      hepatitis A vaccine in children].
AB  - OBJECTIVE: To evaluate the safety, immunogenicity and fit dosage of Healive
      inactivated hepatitis A vaccine (HAV) in children. METHODS: A total of 85
      susceptible aged 4 - 10 years with HAV seronegative children, had been enrolled
      from two adjacent villages in a county. The volunteers were randomized allocated
      into two groups and to receive a priming dose of 250 U/0.5 ml/dose or 500 U/1.0
      ml/dose of Healive vaccine, produced by Sinovac Biotech Co, Ltd. A booster of the
      same dose was given at 12th month. Local and systemic side effects were examined
      and seroconversion rate as well as geometric mean titers of anti-HAV antibody
      were tested at 3-week, 12-month after the primary dose and at 1 month after the
      booster dose. RESULTS: The vaccine was well tolerated in both groups. At 21 days
      after the primary dose, the seroconversion rates were 94.4%, 100.0% and geometric
      mean titers (GMT) were 195 mIU/ml and 370 mIU/ml in 250 U and 500 U groups
      respectively. At 12 months after the primary dose, the seroconversion rate of
      anti-HAV was 100.0%, and GMT raised to 361 mIU/ml, 456 mIU/ml (P > 0.05)
      respectively. One month after the booster dose, GMT raised to 14 893 mIU/ml, 21
      696 mIU/ml. CONCLUSION: GMT of the 0, 12 month schedule was higher than other
      schedule after the booster vaccination. The Healive inactivated vaccine can be
      used for emergency vaccination. The Healive inactivated vaccine produced by
      Sinovac Company Ltd was safe and highly immunogenic. Two hundred and fifty U/dose
      was considered appropriate for children.

PMID- 14687503
TI  - [Study on the disabilities in aged 0-7 years children in Shenzhen, China].
AB  - OBJECTIVE: To explore the prevalence of vision, mental, audibility, language,
      psychiatry, extremity, and influence factors in the 0 - 7 year olds. METHODS: A
      total number of 77,727 0 - 7 year old children living in Shenzhen city were
      tested with tree phase screening under the Chinese standard of evaluation in
      disabilities. RESULTS: The prevalence of all disabilities was 5.59 per thousand
      (adjusted rate was 8.49 per thousand with a false negative of 3.1 per thousand ).
      The prevalence of mental disease was the highest (1.88 per thousand, with
      adjusted rate 3.43 per thousand ), the prevalence of language disability was 1.88
      per thousand (including retarded language development, with adjusted rate 3.43
      per thousand ). The prevalence rates of psychiatry, extremity and audibility
      disability were 1.59 per thousand, 1.56 per thousand, 1.11 per thousand
      respectively with of vision the lowest (0.37 per thousand ). The prevalence of
      all disabilities, audibility, language and mental was on the increase with age.
      The difference was statistically significant. Among all different age groups
      regarding psychiatric disease, the highest fell in the 2 - 4 year olds. The
      prevalence of extremity was not statistically different among age groups. The
      suspected agents of disease which occurred before or during pregnancy took up
      45.7%. CONCLUSION: The prevalence of six kinds disabilities in Shenzhen was about
      10 per thousand lower than that of the samples of the nation in 1989, but two
      times higher than that of similar studies in Japan. The prevalence rates of
      language and psychiatric disease were higher than that of the nation in 1989. The
      causation should be further studied.

PMID- 14687504
TI  - [Spatial analysis on the distribution of hemorrhagic fever with renal syndrome by
      geographic information system in Haidian district, Beijing].
AB  - OBJECTIVE: To analyze the spatial distribution of hemorrhagic fever with renal
      syndrome (HFRS) in Haidian district, Beijing and to explore the geographical
      characteristics of HFRS in highly endemic areas. METHODS: Administration boundary
      layer was established under the background of 1:100,000 map in the ArcInfo 8.1
      software. The HFRS cases from 1997 to 2002 were positioned on the map. Highly
      endemic areas were identified by spatial cluster analysis using SaTScan 3.0
      software. Distribution of HFRS cases was shown in different colors and contours
      by spatial analysis of geographic information system (GIS). RESULTS: Spatial
      Cluster Analysis of confirmed cases of HFRS identified in 1997 - 2002 in Haidian
      district showed that HFRS patients were not randomly distributed. The highly
      endemic areas were founded in Sujiatuo township, Yongfeng township, Shangzhuang
      township, Wenquan town and Bei'anhe township (relative risk = 4.43, P = 0.001). A
      thematic map of HFRS in haidian district was set up. CONCLUSION: HFRS infections
      were not randomly distributed, since the distribution was related to geographic
      environmental factors.

PMID- 14687505
TI  - [Distribution of cerebral vascular hemodynamic indexes].
AB  - OBJECTIVE: To describe the distribution of cerebral vascular hemodynamic indexes
      (CVHI). METHODS: A number of 25,355 age 35 and over were selected in the
      Northeast China by cluster sampling. CVHI were checked during baseline survey and
      were followed to see the occurrence of stroke. Distribution of CVHI among non
      stroke population, individuals prior to the onset of stroke and patients with
      stroke were described. RESULTS: The CVHI accumulative score, V(mean), V(max) and
      V(min) were dramatically decreasing, but RV, Zcv, WV and DR were significantly
      increasing as age increased. V(max), RV and CP were significantly higher in males
      but WV was lower than that of females. The CVHI accumulative score, V(min) and RV
      were 95.0, 10.23 and 75.8 in non-stroke population, 51.25, 6.71 and 122.72 pre
      stroke group, and 55.0, 6.78 and 115.89 in patients with stroke respectively.
      There were significant differences among three groups after controlling of age
      and sex (P < 0.01). CONCLUSION: Variance of CVHI was closely related to age, and
      there appeared a significant abnormal of CVHI before and after stroke.

PMID- 14687506
TI  - [The geographical distribution of ribotypes of Yersinia pestis in China].
AB  - OBJECTIVE: To type and group the Yersinia pestis strains isolated in China to
      clarify the geographical distribution of ribotypes of Yersinia pestis. METHODS:
      Genomic DNA of Yersinia pestis were digested with EcoR I, then hybridized with
      16s-23s-5s rRNA gene probe. RESULTS: These tested strains were divided into 3
      ribotypes, the profiles obtained were relatively homogeneous, with most of them
      differed only by the presence or the absence of 1 - 2 restriction fragments.
      Ribotype A and B were the most common types, which distributed in a large area in
      China while ribotype C was the least, only limited to a small area. There was
      certain correlation between the ribotypes and the plague foci, usually only one
      ribotype was found in one plague foci. CONCLUSION: The ribotypes were stable in
      the plague foci. Correlation between the ribotypes of Yersinia pestis strains and
      their geographical origins was noticed. All 3 ribotypes had different origins,
      however ribotype A and ribotype C seemed to be closer related.

PMID- 14687507
TI  - [Investigation on cagA/vacA dominant genotypes and the coinfection of
      Helicobacter pylori isolates from patients in Zhejiang].
AB  - OBJECTIVE: To determine cagA/vacA dominant genotypes of Helicobacter pylori in
      patients suffering from chronic gastritis (CG) or peptic ulcer (PU), and to
      understand the correlation of different genotype H. pylori infection, coinfection
      and the gastroduodenal diseases. METHODS: H. pylori strains were isolated from
      antrum and corpus samples on 42 patients with CG and 36 patients with PU.
      Polymerase chain reaction was used to detect cagA and the s and m regions of vacA
      in 156 H. pylori isolates from both antrum and corpus. The distribution of H.
      pylori genotypes and coinfection in CG and PU was analyzed. RESULTS: Almost all
      of the isolated H. pylori strains were cagA positive. In region of vacA, only one
      genotype of signal region (s1a) and four genotypes of the middle region (m1, m2,
      m1b and m1b-m2) were found. The proportions of s1a/m1, s1a/m2, s1a/m1b, s1a/m1b
      m2 and coinfection of multiple H. pylori strains in 78 isolates from antrum
      samples were 6.4%, 55.1%, 26.9%, 1.3% and 3.8%; and the related proportions of
      those from corpus samples were 6.4%, 53.8%, 25.6%, 3.8% and 5.1%, respectively.
      Sixteen (20.5%) patients had multiple H. pylori strains with different cagA and
      vacA genotypes, and multiple samples were better than single sample taken from
      one stomach to increase the positive proportion of coinfection. CONCLUSION:
      cagA(+) s1a/m2 was the dominant genotype of H. pylori in the CG or PU patients
      followed by cagA(+) s1a/m1b in the Zhejiang area of China. Some of the patients
      were coinfected with multiple H. pylori strains of different cagA and vacA
      genotypes. However, there was no significant correlation between the genotypes or
      mixed infection with multiple strains, CG or PU.

PMID- 14687508
TI  - [Appraisal on method of temperature to the first appearance of Culex
      tritaeniorhynchus in spring].
AB  - OBJECTIVE: To find out an appraisal method of temperature on the first appearance
      date of Culex tritaeniorhynchus in spring. METHODS: Whole night collection of
      mosquitoes mosquitoes (from 18:00 hours to 06:00 hours of the following day) with
      light traps had been carried out in pig sties every night since 1 March in 1982 -
      1992 and 2001 - 2002 in Fengxian area Shanghai. The adult mosquitoes caught were
      anaesthetized, then identified and counted. The density of mosquitoes was
      calculated by the average number of mosquitos per one trap and one night.
      Comparative analysis of the mean daily air temperature at 7 days before, the
      first appearance date and 1 day after, the first appearance date of Culex
      tritaeniorhynchus. RESULTS: Data of the first appearance data of Culex
      tritaeniorhynchus were judged to mean daily air temperature and cumulative
      temperature on the day of the first appearance of Culex tritaeniorhynchus and the
      day before appearance, or 3 days on the day of the first appearance of Culex
      tritaeniorhynchus and the two days before appearance and the day since appearance
      with a difference less than 1 - 2 day (91.7%). CONCLUSION: The first appearance
      of Culex tritaeniorhynchus in spring accompanied with a course of influence by
      the severe warm air advection from south of China, and lowest mean daily air
      temperature of the first appearance was 11 degrees. Thus the first appearance
      data of Culex tritaeniorhynchus could be deduced and rehabilitated from observed
      values of mean daily air temperature or its forecasting values.

PMID- 14687509
TI  - [Study on the molecular mechanism of apoptosis in esophageal cancer cells induced
      by soybean isoflavone].
AB  - OBJECTIVE: To investigate the function of apoptosis in esophageal cancer cells
      induced by soybean isoflavone, and the relation between this apoptosis and
      expression of bcl-2 and bax. METHODS: In vitro experiments, MTT assay was used to
      determine the cell growth inhibitory rate. Transmission electron microscope and
      TUNEL staining method were used to quantitatively and qualitatively detect the
      apoptosis status of esophageal cancer cell line EC-9706 before and after the
      soybean isoflavone treatment. Immunohistochemical staining and reverse
      transcription-polymerase chain reaction were used to detect the expression of
      apoptosis-regulated gene bcl-2 and bax. RESULTS: Soybean isoflavone inhibited the
      growth of esophageal cancer cell line EC-9706 in a dose- and time-dependent
      manner. Soybean isoflavone induced EC-9706 cells to undergo apoptosis with
      typically apoptotic characteristics, including morphological changes of chromatin
      condensation, chromatin crescent formation, nucleus fragmentation and apoptotic
      body formation by transmission electron microscope and staining positive cells,
      using TUNEL assay. Soybean isoflavone reduced the expression of apoptosis
      regulated gene bcl-2, and improving the expression of apoptosis-regulated gene
      bax. CONCLUSION: Soybean isoflavone seemed to be able to induce the apoptosis in
      esophageal cancer. This type of apoptosis might be mediated by down-expression of
      apoptosis-regulated gene bcl-2 and up-expression of apoptosis-regulated gene bax.

PMID- 14687510
TI  - [Meta-analysis on the effect and adverse reaction on patients with osteoarthritis
      and rheumatoid arthritis treated with non-steroidal anti-inflammatory drugs].
AB  - OBJECTIVE: To observe the rate of efficacy and adverse drug reaction of non
      steroidal anti-inflammatory drugs (NSAIDs) in the population with osteoarthritis
      and rheumatoid arthritis, based on available clinical data. METHODS: Using Meta
      analysis to evaluate the data of effect and safety profile of NSAIDs from 19
      articles on randomized clinical trials published from 1990 to 2001 in Chinese
      journals. The total number of patients enrolled for evaluation on rates of
      effectiveness and adverse drug reaction were 1 732 and 2 925, respectively.
      RESULTS: Data on the effect and safety were comparatively heterogeneous among
      different kinds of NSAIDs. The effective rates (95% CI) were as follows:
      nabunetone, 66.7% (61.9% - 71.4%); meloxicam, 68.4% (59.2% - 77.6%); naproxen,
      64.5% (59.8% - 69.1%); nimesulide, 79.8% (75.7% - 84.0%); ibuprofen, 77.2% (70.7%
      - 83.8%); diclofenac, 77.1% (69.2% - 85.0%); oxaprozin, 65.8% (59.5% - 72.0%).
      Rates of adverse drug reaction (95% CI) were as follows: nabunetone, 16.3% (12.5%
      - 20.0%); meloxicam, 10.2% (4.2% - 16.2%); naproxen, 29.2% (24.8% - 33.6%);
      nimesulide, 20.2% (16.0% - 24.3%); ibuprofen, 16.7% (14.7% - 18.8%); diclofenac,
      19.3% (11.9% - 26.7%); oxaprozin, 12.7% (8.9% - 16.7%) respectively. CONCLUSION:
      The rates of effect and adverse reaction on patients having osteoarthritis and
      rheumatoid arthritis with NSAIDs treatment would largely depend on the drugs
      being used. Within 2 - 8 weeks of treatment, the effective rate and rate of
      adverse drug reaction with commonly used NSAIDs as nabumeton, meloxicam, etc.,
      were 59.2% - 85.0% and 4.2% - 33.6%, respectively.

PMID- 14687511
TI  - [Study on the quality of life in long-term survivors with acute leukemia in
      Shanghai].
AB  - OBJECTIVE: To assess the quality of life (QOL) in long-term survivors with acute
      leukemia (AL). METHODS: Ninety-five long-term survivors with AL drawn from 29
      hospitals in Shanghai during the period 1984 - 1994 were studied. Questionnaire
      FACT-G was completed in order to assess the QOL for long-term survivors with AL.
      RESULTS: Questionnaires assessing QOL were filled in by 95 long-term survivors
      with AL. Majority of the survivor turned out having normal QOL. The average QOL
      score was 85. Patients aged over 60 years old and illiterate had higher QOL
      score. About 50% of the patients had returned to full-time job or school. 12.6%
      of the patients had had secondary diseases due to chemotherapy. Nearly half of
      the married patients were not satisfied with their sexual life. CONCLUSION: Thus,
      prevention of having secondary diseases and to keep sexual function must call for
      serious attention during chemotherapy. The biggest challenge was to prevent
      relapse and the affordability to treatment.

PMID- 14687512
TI  - [Study on the application of artificial neural network on diabetes
      mellitus/insulin-glucose tolerance classification].
AB  - OBJECTIVE: To discuss the potential application of artificial neural network
      (ANN) on the epidemiological classification of disease. METHODS: Learning vector
      quantification neural network (LVQNN) and discriminate analysis were applied to
      data from epidemiological survey in a mine in 1996. RESULTS: The structure of
      LVQNN was 25-->13-->3. The total veracity rates was 96.98%, and 92.45% among the
      abnormal blood glucose individuals. Through stepwise discriminate analysis, the
      discriminate equations were established including 11 variables with a total
      veracity rate of 87.34%, but was 85.53% in the abnormal blood glucose
      individuals. Further analysis on 30 cases with missing values showed that the
      disagreement ratio of LVQ was 1/30, lower than that of discriminate analysis of
      7/30. CONCLUSIONS: Compared to the conventional statistics method, LVQ not only
      showed better prediction precision, but could treat data with missing values
      satisfactorily plus it had no limit to the type or distribution of relevant data,
      thus provided a new powerful method to epidemiologic prediction.

PMID- 14687526
TI  - [Studies on the changes in expression of hypoxia induction factor-1alpha in
      myocardial tissue in severely scalded rats during early postburn stage].
AB  - OBJECTIVE: To investigate the changes in the expression of hypoxia induction
      factor-1alpha (HIF1-alpha) in myocardial tissues in severely scalded rats during
      early postburn stage. METHODS: Male Wistar rats inflicted with 40% TBSA III
      degree scald were employed as the model. The myocardial tissue samples were
      harvested from the left and right ventricles at different postburn time points,
      and samples were also obtained from normal rats as control. The mRNA and protein
      expressions of HIF-1alpha in rat myocardial tissue were determined by RT-PCR and
      Western blot analysis respectively. RESULTS: There was a difference of HIF-1alpha
      expression between left and right ventricles of the normal rats at both
      transcriptional and translational levels, and the mRNA and protein expressions of
      HIF-1alpha in the myocardial tissue of scalded rats were increased dramatically
      at early postburn stage. CONCLUSION: The tolerance to ischemia and hypoxia of the
      rat left ventricle was higher than that of the right ventricle under normal
      condition. An increase in HIF1alpha expression in rat myocardial tissue could be
      induced in severely scalded rats.

PMID- 14687527
TI  - [Protective effects of c-jun anti-sense gene recombinant transfection on rat
      cardiomyocytes inflicted by hypoxia and burn serum].
AB  - OBJECTIVE: To investigate the protective effects of c-jun antisense gene
      recombinant transfection on rat cardiomyocytes inflicted by hypoxia and burn
      serum. METHODS: Cardiomyocytes from Wistar rat were isolated and cultured before
      being divided into normal control (C), transfection (T) and non-transfection (NT)
      groups. C-jun antisense gene recombinant was constructed and transfected into
      cardiomyocytes, which were then treated by hypoxia and burn serum in T group,
      while those in NT group were simply treated by hypoxia and burn serum. The
      changes in the c-jun mRNA expression were determined by RT-PCR at 1, 3 and 7
      hours after the cardiomyocytes being stimulated, and the changes in the
      expressions of c-jun protein, troponin-T (TnT) and beta-tubulin were assayed by
      Western blot. The morphological changes in the cardiomyocytes were observed by LM
      and EM. RESULTS: 1) The expressions of c-jun mRNA and protein in the NT group
      were increased evidently when compared with those in C and T groups. 2) The
      expressions of TnT and beta-tubulin in NT group were decreased evidently in
      contrast to those in C and T groups. In addition, there exhibited evident
      structural derangement, dissolution and fragmentation to granules of
      cardiomyocytes in NT group, while the myocardial cytoskeletal structure was well
      preserved with scarce fragmentation and dissolution in T group. CONCLUSION:
      Increased expression of c-jun in rat cardiomyocytes resulting in myocardial
      injury could be induced by combined treatment of hypoxia and burn serum, while c
      jun antisense gene recombinant transfection might protect rat cardiomyocytes from
      injury.

PMID- 14687528
TI  - [Inhibitory effects of salviae miltiorrhizae and beta-aescinom natrium on the
      postburn acute lung injury in rats].
AB  - OBJECTIVE: To explore the inhibitory effect and its mechanism of salviae
      miltiorrhizae and beta-aescinom natrium on the postburn acute lung injury in
      rats. METHODS: Forty-five rats were randomly divided into sham control (C, n =
      9), sodium chloride group (S, n = 9), salviae miltiorrhizae group (M, n = 9),
      beta-aescinom natrium group (A, n = 9), and combination group (MA, n = 9). The
      rats in M, A and MA groups were subjected to 30% TBSA III degree scald on the
      back, and all the rats were sacrificed at 24 PBH. The blood and pulmonary tissue
      samples were harvested from the rats at 24 PBH for the determination of leukocyte
      adhesiveness/aggregation (LAA) in peripheral blood, myeloperoxidase (MPO),
      malondialdehyde (MDA) and superoxide dismutase (SOD) contents, and the ratio of
      wet to dry weights (W/D) of lung tissue. RESULTS: Compared with those in S group,
      the LAA in blood and the pulmonary tissue contents of MPO, MDA and W/D rate in M
      and A groups, and especially in MA group, were decreased significantly, but the
      SOD content in pulmonary tissue increased obviously in M and A groups, especially
      in MA group. Furthermore, blood LAA was positively correlated with pulmonary
      tissue MDA content. CONCLUSION: Postburn intra-pulmonary agglutination and
      aggregation of PMNs and pulmonary injury by oxygen free radicals (OFRs) and their
      products could be inhibited by either Salviae Miltiorrhizae or beta-aescinom
      natrium. In addition, these agents could also increase the tissue content of
      antioxidant capacity and decrease pulmonary microvascular permeability and lung
      water content. The results indicated that all the agents used might be effective
      in prevention and treatment of postburn pulmonary injury, especially when used
      together.

PMID- 14687529
TI  - [Separation and identification of down-regulated proteomics of intestinal mucosa
      in scalded rats].
AB  - OBJECTIVE: To explore the pathogenesis of postburn intestinal mucosal injury in
      scalded rats. METHODS: The rats inflicted with full thickness burn were employed
      as the model. The two-dimensional electrophoresis (2-DE) was employed to identify
      the down-regulating proteins from the differential proteins in scalded rats. Spot
      detection and matching were performed with Image Master 2D Elite. Mass
      spectrometry was performed on Bruker BIFLEX III TOF. RESULTS: There are 34 points
      of proteins in intestinal mucosa in scalded rats which were down-regulated at 6
      and 12 postburn hours. Among them 22 proteins were employed for the
      identification and analysis. Mitochondrial aconitase, alpha-propionyl -CoA
      carboxylase heavy chain A of F1-ATPase in rat liver, Troponin short-chain of
      hydroxyacyl-coenzyme A dehydrogenase, alpha-subunit of P-electronic transferring
      flavoprotein (ETF) were down-regulating proteins correlated with mitochondria in
      intestinal mucosa in severely scalded rats. Triosephosphate isomerase 1 and
      cytosolic epoxide hydrolase were down-regulating proteins participated in
      metabolism of scalded rats. Fibromodulin, dynein-like protein, Troponin-2 and
      myosin light chain 3 alkali (MLC) were down-regulating proteins correlated with
      cellular skeletal protein. Glucocorticoid-inducible protein, nuclear factor1-B2,
      BRCA1, transcriptive factor EB (estradiol benzoate), beta2 subunit of G-protein,
      N-methyl-D-aspartate receptor1 (NMDAR) were down-regulating proteins participated
      in postburn regulation of intestinal mucosa in scalded rats. T-cell receptor-V
      delta 6 and Ig heavy chain V region protein 1 were down-regulating proteins
      correlated with the immunomodulation of intestinal mucosa in scalded rats.
      CONCLUSION: The down-regulating proteins of intestinal mucosa in scalded rats
      exhibited close relationship with mitochondria.

PMID- 14687530
TI  - [The changes in the prostaglandin level and the prostaglandin transfer factor
      mRNA expression in the intestinal mucosa in scalded rats].
AB  - OBJECTIVE: To explore the changes in the PGE(2) and PGI(2), TXA(2) levels and PGT
      mRNA expression in the intestinal mucosa in scalded rats. METHODS: Wistar rats
      inflicted with TBSA 30% III degree scald were employed as the model. The PGE(2)
      and PGI(2) and TXA(2) contents in the intestinal mucosa were measured by
      radioimmunoassay, and the expression of PGT mRNA was detected by in situ
      hybridization. RESULTS: The PGE(2) and PGI(2) levels in intestinal mucosa were
      increased at 12 postburn hours (PBHs) and thereafter decreased dramatically (P <
      0.05). The TXA(2) level in intestinal mucosa of scalded rats was obviously higher
      than that of normal level at 24 and 48 PBHs (P < 0.05), and the expression of PGT
      mRNA seemed to be increased after scalding. CONCLUSION: The decrease of PGE(2)
      level and the increase of TXA(2) level in the intestinal mucosa of scalded rats
      might be involved in rat mucosal injury, and PGT played an important role in the
      regulation of PGs levels.

PMID- 14687531
TI  - [The clinical staging and tissue bacterial quantification in the diagnosis of
      burn wound sepsis].
AB  - OBJECTIVE: To investigate and re-evaluate the relationship between burn wound
      sepsis and tissue bacterial quantity. METHODS: Thirty-two patients admitted
      during past 5 years were enrolled in the study. Bacterial isolation and quantity
      in burn wound tissue were carried out. Meanwhile clinical signs were evaluated
      for the staging of burn wound sepsis. RESULTS: 1) Bacterial invasion could be
      identified in 123 pieces of tissue samples from 32 patients. Samples with tissue
      bacterial quantity > or = 10(5)/g were found in 82 subeschar tissue samples, and
      41 samples with bacteria <10(5)/g. Subeschar tissue samples with bacterial
      quantity > or = 10(5)/g could be determined in 68 samples from 18 patients, and <
      10(5)/g in 20 samples from 5 cases. In addition, samples of subeschar tissue with
      bacterial quantity > or = 10(5)/g could only be found in some of the samples form
      9 cases. 2) Burn wound sepsis could be classified into I-IV stages according to
      tissue bacterial quantification and clinical signs. CONCLUSION: Burn wound sepsis
      could be established by identification of bacterial invasion into living tissue
      with clinical symptoms of toxemia.

PMID- 14687532
TI  - [Experimental study on the effects of intestinal trefoil factor on intestinal
      epithelial proliferation and its signal transduction mechanism].
AB  - OBJECTIVE: To explore the effects of intestinal trefoil factor (ITF) on
      intestinal epithelial proliferation and its possible signal transduction
      mechanism. METHODS: 1). The intestinal epithelial cytoplasmic membrane was
      isolated and harvested from Wistar rats, and it was treated with various doses of
      ITF in the concentration of 0.01, 0.10, 1.00 and 10.00 micro g/ml. The tyrosine
      protein kinase (TPK) activity from cytoplasmic membrane ITF receptor was
      determined by membrane-bound method. 2). The intestinal epithelial cells 6 (IEC
      6) cultured in vitro were employed in the study. Some of the cells were used as
      normal control, while a group of cells were stimulated by 1 micro g/ml ITF, and
      others were treated by PD098059, SB202190 and SB202474, respectively. The last
      three agents were inhibitors of three members of mitogen-activated protein kinase
      family (MAPKs), i.e. extracellular signal regulated protein kinases (ERKs),
      protein kinase p38 (p38), and stress-activated protein kinase (SAPK). They were
      used before the addition of 1 micro g/ml of ITF. The changes in DNA synthetic
      rate and the MAPK activity of IEC-6 after being treated by above agents were
      assessed by (3)H-TdR incorporation method. RESULTS: ITF receptor possessed TPK
      activity. TPK activity of ITF receptor, MAPKs activity and DNA synthetic rate of
      IEC-6 were increased obviously under the stimulation of ITF (P < 0.01). The above
      ITF effects could be evidently blocked by PD098059 and partially attenuated by
      SB202474. But SB202190 showed no effect in this respect. CONCLUSION: ITF could
      promote intestinal epithelial proliferation and transmit extracellular signals
      mainly by means of ERKs signalling pathway.

PMID- 14687533
TI  - [The effects of epidermal growth factor on the wound healing of deep partial
      thickness burn in rats].
AB  - OBJECTIVE: To observe the effects of recombinant human epidermal growth factor
      (rhEGF) on deep partial thickness burn wound healing. METHODS: The rats were
      inflicted with deep partial thickness burn. The wounds were either treated with
      rhEGF, rhEGF with heparin or isotonic saline, respectively. Wound healing time
      was observed. Wound healing rate, water content and hydroxyproline (OHP) content
      and type I/III collagen ratio in the wound tissue were determined. Cellular DNA
      cycle analysis and histological examination were processed. RESULTS: After the
      application of rhEGF, burn wound healing time was shortened by two days and wound
      content of OHP was increased (P < 0.05), with decreased collagen type I/III ratio
      (P < 0.05). As a result, granulation was enhanced and cellular DNA replication
      was accelerated (P < 0.05). Heparin addition could augment the effects of rhEGF,
      especially on wound healing time (2 days shorter) and granulation. CONCLUSION:
      The wound healing time of the deep partial thickness burn could be accelerated
      markedly by topical application of rhEGF, but early application did not show
      obvious effects. The addition of heparin might further accelerate wound healing.

PMID- 14687534
TI  - [An experimental study on the change in neuropeptide substance P in the burn
      wound skin in scalded rats].
AB  - OBJECTIVE: To investigate the change in neuropeptide substance P (SP) in the burn
      wound skin in scalded rats. METHODS: The SP distribution density in the rat skin
      samples from the burn wound, peri-wound area and remote area of scalded rats were
      determined by immunohistochemistry technique. The mRNA expression of SP was
      observed by in situ hybridization. RESULTS: The distribution density of SP in the
      skin samples from the above three areas decreased obviously since 15 mins
      postburn, dropped to the lowest level during 6 - 12 postburn hou (PBH), and then
      recovered thereafter. Comparatively, the recovery in peri-wound area occurred
      earlier. In addition, there was emigration of macrophage-like large cells with
      positive SP immunoreactivity from local blood vessels in the dermal layer of the
      burn wound and peri-wound areas. The large cells were closely related to the
      local SP-containing nerve fibres at 12 PBHs. Intensified staining of the cells
      was identified at 24 PBHs with the disintegration of the cells into pieces with
      release of large amounts of positive SP immunoreactive granules, followed by
      disappearance of the cells at 48 PBHs. It was indicated by in situ hybridization
      that the preprotachykinin A (PPTA) mRNA encoding and synthesizing SP was
      expressed in various cells at 6 PBHs. CONCLUSION: SP might be synthesized and
      released from cutaneous nerve ending or from local inflammatory cells after skin
      burn injury.

PMID- 14687535
TI  - [Effects of lanthanum chloride on the apoptosis of fibroblasts in trauma tissue].
AB  - OBJECTIVE: To investigate the effects of lanthanum chloride on the apoptosis of
      fibroblasts in trauma tissue. METHODS: Fifty adult female SD rats were used and
      linear incisions were made on the back near the joints of extremities of the
      rats. One of the cuts receiving no treatment was designated as blank control (C).
      0.25 ml of distilled water, lanthanum chloride (50 mmol/L) and the antibody of
      (TGFbeta(1)) transforming growth factor beta(1) (0.2 mg/ml) were respectively
      injected into the both sides of the other three wounds subcutaneously and the
      wounds were divided into simulating control (SC), lanthanum chloride (LC) and
      antibody (A) groups. The fibroblast apoptosis in the wound tissue samples and the
      change in intracellular calcium concentration (Ca(2+)) were determined by flow
      cytometry (FCM) and TUNEL methods on the 14th and 28th day after the injection.
      RESULTS: Apoptosis of fibroblasts was enhanced significantly after 14 days of
      injection in LC and A groups compared with that in C and SC groups (P < 0.05
      approximately 0.01). Furthermore, intracellular Ca(2+) was increased evidently in
      LC group (P < 0.01). CONCLUSION: It is indicated that lanthanum chloride might be
      effective in preventing scar development.

PMID- 14687536
TI  - [Comparison of composite grafting of autoskin with acellular dermal matrix from
      different sources].
AB  - OBJECTIVE: To compare the composite grafts of acellular dermal matrix (ADM) from
      different sources with autoskin. METHODS: Six local white mini pigs were employed
      for the experiment. The pigs were randomly divided into four groups according to
      different skin grafts, i.e. A (human ADM with razor thin autoskin), B (porcine
      ADM with razor thin autoskin), C (razor thin autoskin only), and D (split
      thickness autoskin) as control. The survival rate, the contraction degree of the
      grafts, and the histological changes in grafting area were observed at 2, 4, 8,
      12 and 24 hours after the operation. RESULTS: The grafted area in both A and B
      groups appeared smooth and elastic with satisfactory graft survival. The in
      growth of the host reparative cells such as fibroblast and vascular endothelium
      could be induced by composite grafts of different ADMs with skin grafting. The
      contraction areas in A and B groups seemed bigger than those in C and D groups.
      The tissue structure of grafting areas was similar to that of split thickness
      skin grafting area at 24 post-operation weeks. CONCLUSION: Combination of the
      homogenous and heterogeneous ADMs with autografts exhibited similar biological
      function during the observation period (24 weeks after operation). Xenogenous
      ADMs might have broader clinical applications.

PMID- 14687537
TI  - Ion channels go to Stockholm--this time as proteins.
AB  - The 2003 Nobel Prize in Chemistry was awarded to two structural biologists,
      Roderick Mackinnon of Rockefeller University and Peter Agre of Johns Hopkins
      University, for their groundbreaking work on the structure and function of ion
      channels. In recognition of the outstanding impact that MacKinnon's work has had
      for neuroscience, Chris Miller traces MacKinnon's scientific path to the Nobel
      Prize.

PMID- 14687538
TI  - Mapping by waves. Patterned spontaneous activity regulates retinotopic map
      refinement.
AB  - A role for spontaneous spiking activity in shaping neuronal circuits has
      frequently been debated. Analyses of retinotopy in mutant mice with reduced
      correlated firing among neighboring retinal cells by Grubb et al. and McLaughlin
      et al. in this issue of Neuron indicate the importance of patterned spontaneous
      activity for retinotopic map refinement in subcortical visual targets.

PMID- 14687539
TI  - Episodic memory signals in the rat hippocampus.
AB  - How does the hippocampus signal memory for episodes? In this issue of Neuron,
      Ferbinteanu and Shapiro show that classic place cell activity in the rat
      hippocampus together with robust retrospective and prospective memory signals
      reflects the sequence of past, present, and future events that make up an
      episode.

PMID- 14687540
TI  - Active vision and visual activation in area V4.
AB  - During normal vision, the focus of gaze continually jumps from one important
      image feature to the next. In this issue of Neuron, Mazer and Gallant analyze
      neural activity in higher-level visual cortex during this kind of active visual
      exploration, and they demonstrate a localized enhancement of visual responses
      that predicts the target of the upcoming eye movement.

PMID- 14687541
TI  - Weighing the role of hypothalamic feeding neurotransmitters.
AB  - Growing health problems related to obesity have focused considerable attention on
      a number of neurotransmitters, particularly hypothalamic neuropeptides, involved
      in regulating energy homeostasis and food intake. As the fast-acting transmitters
      GABA and glutamate underlie the majority of fast synaptic activity in the
      hypothalamus, understanding neuropeptide modulation of amino acid transmitter
      actions may be key to a full appreciation of how the brain controls caloric
      balances.

PMID- 14687542
TI  - Learning in spiking neural networks by reinforcement of stochastic synaptic
      transmission.
AB  - It is well-known that chemical synaptic transmission is an unreliable process,
      but the function of such unreliability remains unclear. Here I consider the
      hypothesis that the randomness of synaptic transmission is harnessed by the brain
      for learning, in analogy to the way that genetic mutation is utilized by
      Darwinian evolution. This is possible if synapses are "hedonistic," responding to
      a global reward signal by increasing their probabilities of vesicle release or
      failure, depending on which action immediately preceded reward. Hedonistic
      synapses learn by computing a stochastic approximation to the gradient of the
      average reward. They are compatible with synaptic dynamics such as short-term
      facilitation and depression and with the intricacies of dendritic integration and
      action potential generation. A network of hedonistic synapses can be trained to
      perform a desired computation by administering reward appropriately, as
      illustrated here through numerical simulations of integrate-and-fire model
      neurons.

PMID- 14687543
TI  - Real-time measurement of exocytosis and endocytosis using interference of light.
AB  - We describe a new approach for making real-time measurements of exocytosis and
      endocytosis in neurons and neuroendocrine cells. The method utilizes interference
      reflection microscopy (IRM) to image surface membrane in close contact with a
      glass coverslip (the "footprint"). At the synaptic terminal of retinal bipolar
      cells, the footprint expands during exocytosis and retracts during endocytosis,
      paralleling changes in total surface area measured by capacitance. In chromaffin
      cells, IRM detects the fusion of individual granules as the appearance of bright
      spots within the footprint with spatial and temporal resolution similar to total
      internal reflection fluorescence microscopy. Advantages of IRM over capacitance
      are that it can monitor changes in surface area while cells are electrically
      active and it can be applied to mammalian neurons with relatively small synaptic
      terminals. IRM reveals that vesicles at the synapse of bipolar cells rapidly
      collapse into the surface membrane while secretory granules in chromaffin cells
      do not.

PMID- 14687544
TI  - Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque
      formation, secondary pathology, and premature death.
AB  - Converging evidence suggests that the accumulation of cerebral amyloid beta
      protein (Abeta) in Alzheimer's disease (AD) reflects an imbalance between the
      production and degradation of this self-aggregating peptide. Upregulation of
      proteases that degrade Abeta thus represents a novel therapeutic approach to
      lowering steady-state Abeta levels, but the consequences of sustained
      upregulation in vivo have not been studied. Here we show that transgenic
      overexpression of insulin-degrading enzyme (IDE) or neprilysin (NEP) in neurons
      significantly reduces brain Abeta levels, retards or completely prevents amyloid
      plaque formation and its associated cytopathology, and rescues the premature
      lethality present in amyloid precursor protein (APP) transgenic mice. Our
      findings demonstrate that chronic upregulation of Abeta-degrading proteases
      represents an efficacious therapeutic approach to combating Alzheimer-type
      pathology in vivo.

PMID- 14687545
TI  - Axoplasmic importins enable retrograde injury signaling in lesioned nerve.
AB  - Axoplasmic proteins containing nuclear localization signals (NLS) signal
      retrogradely by an unknown mechanism in injured nerve. Here we demonstrate that
      the importin/karyopherin alpha and beta families underlie this process. We show
      that importins are found in axons at significant distances from the cell body and
      that importin beta protein is increased after nerve lesion by local translation
      of axonal mRNA. This leads to formation of a high-affinity NLS binding complex
      that traffics retrogradely with the motor protein dynein. Trituration of
      synthetic NLS peptide at the injury site of axotomized dorsal root ganglion (DRG)
      neurons delays their regenerative outgrowth, and NLS introduction to sciatic
      nerve concomitantly with a crush injury suppresses the conditioning lesion
      induced transition from arborizing to elongating growth in L4/L5 DRG neurons.
      These data suggest a model whereby lesion-induced upregulation of axonal importin
      beta may enable retrograde transport of signals that modulate the regeneration of
      injured neurons.

PMID- 14687546
TI  - Inactivation of Numb and Numblike in embryonic dorsal forebrain impairs
      neurogenesis and disrupts cortical morphogenesis.
AB  - Numb and Numblike, conserved homologs of Drosophila Numb, have been implicated in
      cortical neurogenesis; however, analysis of their involvement in later stages of
      cortical development has been hampered by early lethality of double mutants in
      previous studies. Using Emx1(IREScre) to induce more restricted inactivation of
      Numb in the dorsal forebrain of numblike null mice beginning at E9.5, we have
      generated viable double mutants that displayed striking brain defects. It was
      thus possible to examine neurogenesis during the later peak phase (E12.5-E16.5).
      Loss of Numb and Numblike in dorsal forebrain resulted in neural progenitor
      hyperproliferation, delayed cell cycle exit, impaired neuronal differentiation,
      and concomitant defects in cortical morphogenesis. These findings reveal novel
      and essential function of Numb and Numblike during the peak period of cortical
      neurogenesis. Further, these double mutant mice provide an unprecedented viable
      animal model for severe brain malformations due to defects in neural progenitor
      cells.

PMID- 14687547
TI  - RORalpha coordinates reciprocal signaling in cerebellar development through sonic
      hedgehog and calcium-dependent pathways.
AB  - The cerebellum provides an excellent system for understanding how afferent and
      target neurons coordinate sequential intercellular signals and cell-autonomous
      genetic programs in development. Mutations in the orphan nuclear receptor
      RORalpha block Purkinje cell differentiation with a secondary loss of afferent
      granule cells. We show that early transcriptional targets of RORalpha include
      both mitogenic signals for afferent progenitors and signal transduction genes
      required to process their subsequent synaptic input. RORalpha acts through
      recruitment of gene-specific sets of transcriptional cofactors, including beta
      catenin, p300, and Tip60, but appears independent of CBP. One target promoter is
      Sonic hedgehog, and recombinant Sonic hedgehog restores granule precursor
      proliferation in RORalpha-deficient cerebellum. Our results suggest a link
      between RORalpha and beta-catenin pathways, confirm that a nuclear receptor
      employs distinct coactivator complexes at different target genes, and provide a
      logic for early RORalpha expression in coordinating expression of genes required
      for reciprocal signals in cerebellar development.

PMID- 14687548
TI  - Loss of TGF-beta 1 leads to increased neuronal cell death and microgliosis in
      mouse brain.
AB  - TGF-beta1 is a key regulator of diverse biological processes in many tissues and
      cell types, but its exact function in the developing and adult mammalian CNS is
      still unknown. We report that lack of TGF-beta1 expression in neonatal Tgfb1(-/-)
      mice results in a widespread increase in degenerating neurons accompanied by
      reduced expression of synaptophysin and laminin and a prominent microgliosis.
      Lack of TGF-beta1 also strongly reduces survival of primary neurons cultured from
      Tgfb1(-/-) mice. TGF-beta1 deficiency in adult Tgfb1(-/+) mice results in
      increased neuronal susceptibility to excitotoxic injury, whereas astroglial
      overexpression of TGF-beta1 protects adult mice against neurodegeneration in
      acute, excitotoxic and chronic injury paradigms. This study reveals a
      nonredundant function for TGF-beta1 in maintaining neuronal integrity and
      survival of CNS neurons and in regulating microglial activation. Because
      individual TGF-beta1 expression levels in the brain vary considerably between
      humans, this finding could have important implications for susceptibility to
      neurodegeneration.

PMID- 14687549
TI  - Retinotopic map refinement requires spontaneous retinal waves during a brief
      critical period of development.
AB  - During retinocollicular map development, spontaneous waves of action potentials
      spread across the retina, correlating activity among neighboring retinal ganglion
      cells (RGCs). To address the role of retinal waves in topographic map
      development, we examined wave dynamics and retinocollicular projections in mice
      lacking the beta2 subunit of the nicotinic acetylcholine receptor. beta2(-/-)
      mice lack waves during the first postnatal week, but RGCs have high levels of
      uncorrelated firing. By P8, the wild-type retinocollicular projection remodels
      into a refined map characterized by axons of neighboring RGCs forming focal
      termination zones (TZs) of overlapping arbors. In contrast, in P8 beta2(-/-)
      mice, neighboring RGC axons form large TZs characterized by broadly distributed
      arbors. At P8, glutamatergic retinal waves appear in beta2(-/-) mice, and later,
      visually patterned activity appears, but the diffuse TZs fail to remodel. Thus,
      spontaneous retinal waves that correlate RGC activity are required for
      retinotopic map remodeling during a brief early critical period.

PMID- 14687550
TI  - Abnormal functional organization in the dorsal lateral geniculate nucleus of mice
      lacking the beta 2 subunit of the nicotinic acetylcholine receptor.
AB  - Spontaneous activity patterns in the developing retina appear important for the
      functional organization of the visual system. We show here that an absence of
      early retinal waves in mice lacking the beta2 subunit of the nicotinic
      acetylcholine receptor (nAChR) is associated with both gain and loss of
      functional organization in the dorsal lateral geniculate nucleus (dLGN).
      Anatomical studies show normal gross retinotopy in the beta2(-/-) dLGN but
      suggest reduced topographic precision in the retinogeniculate projection.
      Physiological recordings reveal normal topography in the dorsoventral visual axis
      but a lack of fine-scale mapping in the nasotemporal visual plane. In contrast,
      unlike wild-type mice, on- and off-center cells in the beta2(-/-) dLGN are
      spatially segregated. The presence of the beta2 subunit of the nAChR in the CNS
      is therefore important for normal functional organization in the retinogeniculate
      projection.

PMID- 14687551
TI  - Ectopic release of synaptic vesicles.
AB  - Exocytosis of synaptic vesicles is generally assumed to occur only at
      ultrastructurally defined presynaptic active zones. If release is restricted to
      these sites, receptors not located within the synaptic cleft must be activated by
      transmitter that diffuses out of the cleft or not be activated at all. Here we
      report that AMPA receptor-mediated quantal events resulting from climbing fiber
      release are observed in Bergmann glial cells in the cerebellar cortex. These
      quantal events are not coincident with quanta recorded in neighboring Purkinje
      cells which receive input from the same climbing fiber. As Bergmann glial
      membranes are excluded from the synaptic cleft, we propose that exocytosis can
      occur from climbing fiber release sites located directly across from Bergmann
      glial membranes. Such ectopic release may account for the majority of the
      Bergmann glial AMPA response evoked by climbing fiber stimulation.

PMID- 14687552
TI  - Regulation of the Ca2+/CaM-responsive pool of CaMKII by scaffold-dependent
      autophosphorylation.
AB  - CaMKII is critical for structural and functional plasticity. Here we show that
      Camguk (Cmg), the Drosophila homolog of CASK/Lin-2, associates in an ATP
      regulated manner with CaMKII to catalyze formation of a pool of calcium
      insensitive CaMKII. In the presence of Ca(2+)/CaM, CaMKII complexed to Cmg can
      autophosphorylate at T287 and become constitutively active. In the absence of
      Ca(2+)/CaM, ATP hydrolysis results in phosphorylation of T306 and inactivation of
      CaMKII. Cmg coexpression suppresses CaMKII activity in transfected cells, and the
      level of Cmg expression in Drosophila modulates postsynaptic T306
      phosphorylation. These results suggest that Cmg, in the presence of Ca(2+)/CaM,
      can provide a localized source of active kinase. When Ca(2+)/CaM or synaptic
      activity is low, Cmg promotes inactivating autophosphorylation, producing CaMKII
      that requires phosphatase to reactivate. This interaction provides a mechanism by
      which the active postsynaptic pool of CaMKII can be controlled locally to
      differentiate active and inactive synapses.

PMID- 14687553
TI  - Glutamatergic plasticity by synaptic delivery of GluR-B(long)-containing AMPA
      receptors.
AB  - Activity-driven delivery of AMPA receptors is proposed to mediate glutamatergic
      synaptic plasticity, both during development and learning. In hippocampal CA1
      principal neurons, such trafficking is primarily mediated by the abundant GluR-A
      subunit. We now report a study of GluR-B(long), a C-terminal splice variant of
      the GluR-B subunit. GluR-B(long) synaptic delivery is regulated by two forms of
      activity. Spontaneous synaptic activity-driven GluR-B(long) transport maintains
      one-third of the steady-state AMPA receptor-mediated responses, while GluR
      B(long) delivery following the induction of LTP is responsible for approximately
      50% of the resulting potentiation at the hippocampal CA3 to CA1 synapses at the
      time of GluR-B(long) peak expression-the second postnatal week. Trafficking of
      GluR-B(long)-containing receptors thus mediates a GluR-A-independent form of
      glutamatergic synaptic plasticity in the juvenile hippocampus.

PMID- 14687554
TI  - Basal forebrain cholinergic modulation of auditory activity in the zebra finch
      song system.
AB  - The cholinergic basis of auditory "gating" in the sensorimotor nucleus HVc and
      its efferent target robustus archistriatalis (RA) was investigated in
      anesthetized zebra finches. Injections of cholinergic agonists carbachol or
      muscarine into HVc strongly affected discharge rates and diminished auditory
      responsiveness in both HVc and its target RA, changes toward an awake-like
      condition. HVc nicotine injections produced similar strong effects in HVc, but
      weaker and inconsistent effects in RA. Stimulation of basal forebrain (BF)
      produced an initial transient network shutdown followed by diminished auditory
      responsiveness in HVc and RA. All stimulation effects were blocked when preceded
      by HVc injections of nicotinic or muscarinic antagonists. Thus, BF cholinergic
      modulation of song system auditory activity acting via functionally distinct HVc
      circuits can contribute to auditory gating. We hypothesize that wakeful BF
      activity levels block sensory input to motor systems and adaptively change during
      behavior to allow sensorimotor feedback such as auditory feedback during singing.

PMID- 14687555
TI  - Prospective and retrospective memory coding in the hippocampus.
AB  - The effect of memory on hippocampal neuronal activity was assessed as rats
      performed a spatial task that was impaired by fornix lesions. The influences of
      current location, recently entered places, and places about to be entered were
      compared. Three new findings emerged. (1) Current, retrospective, and prospective
      coding were common and recorded simultaneously in neural ensembles. (2) The
      origin of journeys influenced firing even when rats made detours, showing that
      recent memory could modulate neuronal activity more than spatial trajectory. (3)
      Diminished retrospective coding and, more markedly, reduced prospective coding in
      error trials suggested that the neuronal signal was important for task
      performance. The population of hippocampal neurons thus encoded information about
      the recent past, the present, and the imminent future, consistent with a neuronal
      mechanism for episodic memory.

PMID- 14687556
TI  - Goal-related activity in V4 during free viewing visual search. Evidence for a
      ventral stream visual salience map.
AB  - Natural exploration of complex visual scenes depends on saccadic eye movements
      toward important locations. Saccade targeting is thought to be mediated by a
      retinotopic map that represents the locations of salient features. In this
      report, we demonstrate that extrastriate ventral area V4 contains a retinotopic
      salience map that guides exploratory eye movements during a naturalistic free
      viewing visual search task. In more than half of recorded cells, visually driven
      activity is enhanced prior to saccades that move the fovea toward the location
      previously occupied by a neuron's spatial receptive field. This correlation
      suggests that bottom-up processing in V4 influences the oculomotor planning
      process. Half of the neurons also exhibit top-down modulation of visual responses
      that depends on search target identity but not visual stimulation. Convergence of
      bottom-up and top-down processing streams in area V4 results in an adaptive,
      dynamic map of salience that guides oculomotor planning during natural vision.

PMID- 14687557
TI  - Direct activation of the ventral striatum in anticipation of aversive stimuli.
AB  - The brain "reward" system, centered on the limbic ventral striatum, plays a
      critical role in the response to pleasure and pain. The ventral striatum is
      activated in animal and human studies during anticipation of
      appetitive/pleasurable events, but its role in aversive/painful events is less
      clear. Here we present data from three human fMRI studies based on aversive
      conditioning using unpleasant cutaneous electrical stimulation and show that the
      ventral striatum is reliably activated. This activation is observed during
      anticipation and is not a consequence of relief after the aversive event.
      Further, the ventral striatum is activated in anticipation regardless of whether
      there is an opportunity to avoid the aversive stimulus or not. Our data suggest
      that the ventral striatum, a crucial element of the brain "reward" system, is
      directly activated in anticipation of aversive stimuli.

PMID- 14687558
TI  - Binding of plasminogen to Pseudomonas aeruginosa results in formation of surface
      associated plasmin and enhanced bacterial invasiveness.
AB  - The interaction of Pseudomonas aeruginosa with plasminogen (Plg) is herein
      reported. Plg bound similarly to laboratory and clinical P. aeruginosa isolates
      from blood of septicemic patients and stools of asymptomatic carriers. No
      difference in Plg capture was detected between the piliated PAK strain and its
      isogenic nonpiliated mutant. Western immunoblotting results suggested that low
      molecular weight nonpilus adhesins from the bacterial outer membranes accounted
      for the Plg capture. Bacteria-bound Plg was converted to bioactive plasmin in the
      presence of exogenous urokinase-type Plg activator. The presence of surface-bound
      plasmin enhanced significantly the P. aeruginosa capability to invade fibrin gels
      and a reconstituted basement membrane matrix. These findings support the concept
      that Plg capture by P. aeruginosa may represent a mechanism which offers
      advantages to bacterial invasiveness through tissue barriers.

PMID- 14687559
TI  - Mycobacterium avium-superoxide dismutase binds to epithelial cell aldolase,
      glyceraldehyde-3-phosphate dehydrogenase and cyclophilin A.
AB  - Mycobacterium avium complex (MAC) adheres, invades and multiplies inside
      epithelial cells. Earlier, we demonstrated two MAC protein adhesins, 25 and 31
      kDa, binding with HEp-2 cells. The 25 kDa MAC adhesin was found to be superoxide
      dismutase (SOD). In this study, epithelial cell (HEp-2 and A549) ligands for MAC
      SOD were identified by probing two-dimensional western blots of epithelial
      extracts with MAC proteins followed by monoclonal anti-MAC-SOD antibodies. Three
      epithelial cell proteins with molecular masses 43, 40 and 18 kDa, present in both
      membrane and cytosolic fractions, were found to bind with MAC-SOD. Based on the N
      terminal amino acid sequences, the 43, 40 and 18 kDa epithelial proteins were
      identified as aldolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and
      cyclophilin A (CypA), respectively. Furthermore, MAC-SOD was found to bind to
      purified rabbit muscle aldolase, GAPDH and recombinant CypA in western blotting.

PMID- 14687560
TI  - Impairment of Brucella growth in human macrophagic cells that produce nitric
      oxide.
AB  - In mice, nitric oxide (NO) production by inducible NO synthase (iNOS), is a
      component of the control of Brucella infection. In humans, the involvement of
      iNOS in infection is still a matter of debate. Based on in vitro experiments, it
      was recently postulated that in humans, Brucella infection tends to become
      chronic because NO cannot exert its deleterious effect. In fact, conditions
      allowing NO production by human macrophages in culture are poorly defined,
      rendering the in vitro study of NO function difficult. Using DFGiNOS U937
      macrophagic cells engineered to produce NO and U937 cells activated by ligation
      of IgE receptors, we showed that the intracellular development of Brucella was
      impaired in human macrophages, which produced NO. Although Brucella-infected
      human macrophagic phagocytes did not release NO in commonly used models of
      infection, the machinery required to produce NO was expressed in these cells and
      could be triggered by cell membrane receptors present on the infected cells.
      Therefore, the lack of NO production in isolated human macrophages infected by
      Brucella under in vitro conditions did not exclude a possible involvement of NO
      in the control of human brucellosis.

PMID- 14687561
TI  - Oligosaccharide receptor mimics inhibit Legionella pneumophila attachment to
      human respiratory epithelial cells.
AB  - Legionnaire's disease is caused by the intracellular pathogen Legionella
      pneumophila, presenting as an acute pneumonia. Attachment is the key step during
      infection, often relying on an interaction between host cell oligosaccharides and
      bacterial adhesins. Inhibition of this interaction by receptor mimics offers
      possible novel therapeutic treatments. L. pneumophila attachment to the A549 cell
      line was significantly reduced by treatment with tunicamycin (73.6%) and sodium
      metaperiodate (63.7%). This indicates the importance of cell surface
      oligosaccharide chains in adhesion. A number of putative anti-adhesion compounds
      inhibited attachment to the A549 and U937 cell lines. The most inhibitory
      compounds were polymeric saccharides, GalNAcbeta1-4Gal, Galbeta1-4GlcNAc and para
      nitrophenol. These compounds inhibited adhesion to a range of human respiratory
      cell lines, including nasal epithelial, bronchial epithelial and alveolar
      epithelial cell lines and the human monocytic cell line, U937. Some eukaryotic
      receptors for L. pneumophila were determined to be the glycolipids, asialo-GM1
      and asialo-GM2 that contain the inhibitory saccharide moiety, GalNAcbeta1-4Gal.
      The identified compounds have the potential to be used as novel treatments for
      Legionnaire's disease.

PMID- 14687562
TI  - Rapid and transient activation of gene expression in peripheral blood mononuclear
      cells from Johne's disease positive cows exposed to Mycobacterium
      paratuberculosis in vitro.
AB  - Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the
      causative agent of Johne's disease in ruminants. M. paratuberculosis is a slow
      growing intracellular bacterium and infections with M. paratuberculosis can
      persist in a subclinical state for several years. An early and appropriate T cell
      mediated cytotoxic response (Th1-like) to M. paratuberculosis infection is often
      replaced with an antibody or Th 2-like response as infected animals move toward a
      progressively more clinical state. The reasons for this shift in immune response
      are unknown. Recent studies suggest that in vitro exposure of peripheral blood
      mononuclear cells (PBMCs) from Johne's disease positive cows to M.
      paratuberculosis for 18-24 h results in suppressed expression of numerous immune
      cell genes. This effect appears at odds with the notion that immune cells from
      infected cows would respond to M. paratuberculosis-specific antigens in a
      vigorous and positive manner. In this report, we detail experiments designed to
      test the hypothesis that many positive changes in PBMC gene expression induced by
      M. paratuberculosis in vitro are transient, being rapidly suppressed by as yet
      unknown mechanisms. Our results demonstrate that, indeed, in vitro stimulation
      with M. paratuberculosis induces rapid changes in infected cow PBMC gene
      expression (within 2-4 h of exposure) and that many of these changes are no
      longer evident by 8-16 h of exposure to M. paratuberculosis. Although precise
      mechanisms responsible for rapid M. paratuberculosis-mediated activation of PBMC
      gene expression and the loss thereof remain to be determined, our novel results
      suggest that PBMCs from Johne's disease positive cows are indeed capable of
      vigorously responding to M. paratuberculosis and that, for many genes, this
      response is tempered within 8 h of exposure.

PMID- 14687563
TI  - Structure of the Shigella dysenteriae 7 O antigen gene cluster and identification
      of its antigen specific genes.
AB  - Shigella strains are human pathogens. The O antigen gene cluster of Shigella
      dysenteriae O7 was sequenced and analyzed. It contains genes for synthesis of
      nucleotide sugars including UDP-2-acetamido-2-deoxy-D-galacturonamide, UDP-2
      acetamido-2-deoxy-D-galacturonic acid and dTDP-4-amino-4,6-dideoxy-D-glucose.
      Also found in the gene cluster are genes encoding O unit flippase, O antigen
      polymerase and sugar transferases. The Escherichia coli O121 O antigen, which is
      present in an important Shiga toxin-producing strain, has the same structure as
      that of S. dysenteriae O7, and we found that the gene clusters also had the same
      genes and organization. Four genes specific to S. dysenteriae O7 and E. coli O121
      were identified by PCR screening against representatives of 186 E. coli
      (including Shigella) O serotypes. E. coli O121 and S. dysenteriae O7 isolates can
      be distinguished by PCR of the H antigen fliC gene.

PMID- 14687564
TI  - Phage integrases: biology and applications.
AB  - Phage integrases are enzymes that mediate unidirectional site-specific
      recombination between two DNA recognition sequences, the phage attachment site,
      attP, and the bacterial attachment site, attB. Integrases may be grouped into two
      major families, the tyrosine recombinases and the serine recombinases, based on
      their mode of catalysis. Tyrosine family integrases, such as lambda integrase,
      utilize a catalytic tyrosine to mediate strand cleavage, tend to recognize longer
      attP sequences, and require other proteins encoded by the phage or the host
      bacteria. Phage integrases from the serine family are larger, use a catalytic
      serine for strand cleavage, recognize shorter attP sequences, and do not require
      host cofactors. Phage integrases mediate efficient site-specific recombination
      between two different sequences that are relatively short, yet long enough to be
      specific on a genomic scale. These properties give phage integrases growing
      importance for the genetic manipulation of living eukaryotic cells, especially
      those with large genomes such as mammals and most plants, for which there are few
      tools for precise manipulation of the genome. Integrases of the serine family
      have been shown to work efficiently in mammalian cells, mediating efficient
      integration at introduced att sites or native sequences that have partial
      identity to att sites. This reaction has applications in areas such as gene
      therapy, construction of transgenic organisms, and manipulation of cell lines.
      Directed evolution can be used to increase further the affinity of an integrase
      for a particular native sequence, opening up additional applications for genomic
      modification.

PMID- 14687565
TI  - The solution structure of ribosomal protein L18 from Bacillus stearothermophilus.
AB  - A medium resolution solution structure has been obtained for L18 from Bacillus
      stearothermophilus (BstL18), a ribosomal protein that stabilizes the tertiary
      structure of 5S rRNA and mediates its interaction with the rest of the large
      subunit. The N-terminal 22 amino acid residues of BstL18 are unstructured in
      solution. Its remaining 98 residues form a globular domain that has the same
      topology as the globular domains of other L18s, but the orientation of helices is
      different. This conformational peculiarity should not prevent BstL18 from
      functioning in the ribosome the same way as other L18s.

PMID- 14687566
TI  - Studies of the Escherichia coli Rsd-sigma70 complex.
AB  - Escherichia coli Rsd protein was previously identified on the basis of its
      binding to the RNA polymerase sigma(70) subunit. The Rsd-sigma(70) complex has
      been studied using different methods. Our data show that Rsd associates with
      sigma(70) to form a complex with a stoichiometry of 1:1. Alanine scanning and
      deletion mutagenesis were used to locate regions of sigma(70) that are required
      for the formation of the Rsd-sigma(70) complex.

PMID- 14687567
TI  - Methionine adenosyltransferase as a useful molecular systematics tool revealed by
      phylogenetic and structural analyses.
AB  - Structural and phylogenetic relationships among Bacteria and Eukaryota were
      analyzed by examining 292 methionine adenosyltransferase (MAT) amino acid
      sequences with respect to the crystal structure of this enzyme established for
      Escherichia coli and rat liver. Approximately 30% of MAT residues were found to
      be identical in all species. Five highly conserved amino acid sequence blocks did
      not vary in the MAT family. We detected specific structural features that
      correlated with sequence signatures for several clades, allowing taxonomical
      identification by sequence analysis. In addition, the number of amino acid
      residues in the loop connecting beta-strands A2 and A3 served to clearly
      distinguish sequences between eukaryotes and eubacteria. The molecular phylogeny
      of MAT genes in eukaryotes can be explained in terms of functional
      diversification coupled to gene duplication or alternative splicing and
      adaptation through strong structural constraints. Sequence analyses and
      intron/exon junction positions among nematodes, arthropods and vertebrates
      support the traditional Coelomata hypothesis. In vertebrates, the liver MAT I
      isoenzyme has gradually adapted its sequence towards one providing a more
      specific liver function. MAT phylogeny also served to cluster the major bacterial
      groups, demonstrating the superior phylogenetic performance of this ubiquitous,
      housekeeping gene in reconstructing the evolutionary history of distant
      relatives.

PMID- 14687568
TI  - Characterization of a trp RNA-binding attenuation protein (TRAP) mutant with
      tryptophan independent RNA binding activity.
AB  - TRAP (trp RNA-binding attenuation protein) is an 11 subunit RNA-binding protein
      that regulates expression of genes involved in tryptophan metabolism (trp) in
      Bacillus subtilis in response to changes in intracellular tryptophan
      concentration. When activated by binding up to 11 tryptophan residues, TRAP binds
      to the mRNAs of several trp genes and down-regulates their expression. Recently,
      a TRAP mutant was found that binds RNA in the absence of tryptophan. In this
      mutant protein, Thr30, which is part of the tryptophan-binding site, is replaced
      with Val (T30V). We have compared the RNA-binding properties of T30V and wild
      type (WT) TRAP, as well as of a series of hetero-11-mers containing mixtures of
      WT and T30V TRAP subunits. The most significant difference between the
      interaction of T30V and WT TRAP with RNA is that the affinity of T30V TRAP is
      more dependent on ionic strength. Analysis of the hetero-11-mers allowed us to
      examine how subunits interact within an 11-mer with regard to binding to
      tryptophan or RNA. Our data suggest that individual subunits retain properties
      similar to those observed when they are in homo-11-mers and that individual G/UAG
      triplets within the RNA can bind to TRAP differently.

PMID- 14687569
TI  - Asymmetric removal of supercoils suggests how topoisomerase II simplifies DNA
      topology.
AB  - Type-IIA topoisomerases consume ATP as they catalyse the interconversion of DNA
      topoisomers by transporting one DNA segment through a transient break in another.
      It remains unclear how their activity simplifies the topology of DNA below
      equilibrium values. Here we report that eukaryotic topoisomerase II narrows the
      thermal distribution of DNA supercoils, by mainly removing negative DNA
      crossings. Surprisingly, this asymmetry in supercoil removal is not due to
      deformation of the DNA before strand passage. Topoisomerase II neither bends nor
      alters the helical conformation of the interacting DNA. Rather, it appears to
      interact with a third DNA segment, in addition to the gated and the transported
      segments. Remarkably, the simultaneous interaction with three DNA segments
      accounts for the asymmetric removal of supercoils in relaxed DNA and gives a clue
      to how topoisomerase II simplifies the topology of DNA against the thermal drive.

PMID- 14687570
TI  - Features of the plasmid pMV158-encoded MobM, a protein involved in its
      mobilization.
AB  - The streptococcal promiscuous plasmid pMV158 can be mobilized between a number of
      bacterial species by means of three elements: (i) the plasmid-encoded nicking
      closing protein MobM, involved in the initiation and termination of the
      conjugative transfer; (ii) the DNA sequence where the MobM-mediated nick takes
      place (the oriT(pMV158)); and (iii) the function(s) provided by auxiliary
      plasmids. MobM belongs to the Pre/Mob family of plasmid-encoded DNA-relaxing
      proteins (relaxases). Purified MobM protein has been used to assay cleavage
      conditions on plasmid supercoiled DNA. Some structural features of MobM have been
      addressed by analytical ultracentrifugation, circular dichroism, thermal
      denaturation, and fluorescence emission. The protein behaved as a dimer of
      identical subunits with an ellipsoidal shape. MobM showed a high (about 60%)
      alpha-helical content and a midpoint denaturation of about 40 degrees C. Cell
      fractionation assays showed that MobM was associated to the cell membrane. This
      association was abolished when a great alteration was introduced within a
      putative coiled-coil located at the C-terminal region of the protein. Emission
      fluorescence suggested that the three Trp residues of MobM are located within a
      hydrophobic environment. A molecular model of MobM on the known structure of
      colicin Ia has been built.

PMID- 14687571
TI  - Positive correlation between DNA polymerase alpha-primase pausing and mutagenesis
      within polypyrimidine/polypurine microsatellite sequences.
AB  - Microsatellite DNA sequences are ubiquitous in the human genome, and mutation
      rates of these repetitive sequences vary with respect to DNA sequence as well as
      length. We have analyzed polymerase-DNA interactions as a function of
      microsatellite sequence, using polypyrimidine/polypurine di- and tetranucleotide
      alleles representative of those found in the human genome. Using an in vitro
      primer extension assay and the mammalian DNA polymerase alpha-primase complex, we
      have observed a polymerase termination profile for each microsatellite that is
      unique to that allele. Interestingly, a periodic termination profile with an
      interval size (9-11 nucleotides) unrelated to microsatellite unit length was
      observed for the [TC](20) and [TTCC](9) templates. In contrast, a unit-punctuated
      polymerase termination profile was found for the longer polypurine templates. We
      detected strong polymerase pauses within the [TC](20) allele at low reaction pH
      which were eliminated by the addition of deaza-dGTP, consistent with these
      specific pauses being a consequence of triplex DNA formation during DNA
      synthesis. Quantitatively, a strand bias was observed in the primer extension
      assay, in that polymerase synthesis termination is more intense when the
      polypurine sequence serves as the template, relative to its complementary
      polypyrimidine sequence. The HSV-tk forward mutation assay was utilized to
      determine the corresponding polymerase alpha-primase error frequencies and
      specificities at the microsatellite alleles. A higher microsatellite polymerase
      error frequency (50x10(-4) to 60x10(-4)) was measured when polypurine sequences
      serve as templates for DNA synthesis, relative to the polypyrimidine template
      (18x10(-4)). Thus, a positive correlation exists between polymerase alpha-primase
      pausing and mutagenesis within microsatellite DNA alleles.

PMID- 14687572
TI  - The first structure of a bacterial class B Acid phosphatase reveals further
      structural heterogeneity among phosphatases of the haloacid dehalogenase fold.
AB  - AphA is a periplasmic acid phosphatase of Escherichia coli belonging to class B
      bacterial phosphatases, which is part of the DDDD superfamily of
      phosphohydrolases. The crystal structure of AphA has been determined at 2.2A and
      its resolution extended to 1.7A on an AuCl(3) derivative. This represents the
      first crystal structure of a class B bacterial phosphatase. Despite the lack of
      sequence homology, the AphA structure reveals a haloacid dehalogenase-like fold.
      This finding suggests that this fold could be conserved among members of the DDDD
      superfamily of phosphohydrolases. The active enzyme is a homotetramer built by
      using an extended N-terminal arm intertwining the four monomers. The active site
      of the native enzyme, as prepared, hosts a magnesium ion, which can be replaced
      by other metal ions. The structure explains the non-specific behaviour of AphA
      towards substrates, while a structure-based alignment with other phosphatases
      provides clues about the catalytic mechanism.

PMID- 14687573
TI  - Latent LytM at 1.3A resolution.
AB  - LytM, an autolysin from Staphylococcus aureus, is a Zn(2+)-dependent glycyl
      glycine endopeptidase with a characteristic HxH motif that belongs to the
      lysostaphin-type (MEROPS M23/37) of metallopeptidases. Here, we present the 1.3A
      crystal structure of LytM, the first structure of a lysostaphin-type peptidase.
      In the LytM structure, the Zn(2+) is tetrahedrally coordinated by the side-chains
      of N117, H210, D214 and H293, the second histidine of the HxH motif. Although
      close to the active-site, H291, the first histidine of the HxH motif, is not
      directly involved in Zn(2+)-coordination, and there is no water molecule in the
      coordination sphere of the Zn(2+), suggesting that the crystal structure shows a
      latent form of the enzyme. Although LytM has not previously been considered as a
      proenzyme, we show that a truncated version of LytM that lacks the N-terminal
      part with the poorly conserved Zn(2+) ligand N117 has much higher specific
      activity than full-length enzyme. This observation is consistent with the known
      removal of profragments in other lysostaphin-type proteins and with a prior
      observation of an active LytM degradation fragment in S.aureus supernatant. The
      "asparagine switch" in LytM is analogous to the "cysteine switch" in pro-matrix
      metalloproteases.

PMID- 14687574
TI  - Crystal structure of fervidolysin from Fervidobacterium pennivorans, a
      keratinolytic enzyme related to subtilisin.
AB  - Structure-forming fibrous proteins like keratins, gelatins and collagens are
      degraded only by a few proteases as their tight packing limits access to the
      potential cleavage sites. To understand the keratin degradation in detail, we
      describe the first crystal structure of a keratin-degrading enzyme (keratinase),
      fervidolysin, from Fervidobacterium pennivorans as an immature form with
      propeptide (PD)-bound. The 1.7A resolution crystal structure shows that the
      protease is composed of four domains: a catalytic domain (CD), two beta-sandwich
      domains (SDs), and the PD domain. A structural alignment shows a distant
      relationship between the PD-CD substructure of fervidolysin and pro-subtilisin E.
      Tight binding of PD to the remaining part of the protease is mediated by hydrogen
      bonds along the domain surfaces and around the active cleft, and by the clamps to
      SD1 and SD2. The crystal structure of this multi-domain protein fervidolysin
      provides insights into proenzyme activation and the role of non-catalytic
      domains, suggesting a functional relationship to the fibronectin (FN)-like
      domains of the human promatrix metalloprotease-2 (proMMP-2) that degrades the
      fibrous polymeric substrate gelatin.

PMID- 14687575
TI  - Mycobacterium tuberculosis ribose-5-phosphate isomerase has a known fold, but a
      novel active site.
AB  - Ribose-5-phosphate isomerases (EC 5.3.1.6) inter-convert ribose-5-phosphate and
      ribulose-5-phosphate. This reaction allows the synthesis of ribose from other
      sugars, as well a means for salvage of carbohydrates after nucleotide breakdown.
      Two unrelated types of enzyme are known to catalyze the isomerization. The most
      common one, RpiA, is present in almost all organisms. The second type, RpiB, is
      found in many bacterial species.Here, we demonstrate that the RpiB from
      Mycobacterium tuberculosis (Rv2465c) has catalytic properties very similar to
      those previously reported for the Escherichia coli RpiB enzyme. Further, we
      report the structure of the mycobacterial enzyme, solved by molecular replacement
      and refined to 1.88A resolution. Comparison with the E.coli structure shows that
      there are important differences in the two active sites, including a change in
      the position and nature of the catalytic base. Sequence comparisons reveal that
      the M.tuberculosis and E.coli RpiB enzymes are in fact representative of two
      distinct sub-families. The mycobacterial enzyme represents a type found only in
      actinobacteria, while the enzyme from E.coli is typical of that seen in many
      other bacterial proteomes. Both RpiBs are very different from RpiA in structure
      as well as in the construction of the active site. Docking studies allow
      additional insights into the reactions of all three enzymes, and show that many
      features of the mechanism are preserved despite the different catalytic
      components.

PMID- 14687576
TI  - Complex structures of Thermoactinomyces vulgaris R-47 alpha-amylase 1 with malto
      oligosaccharides demonstrate the role of domain N acting as a starch-binding
      domain.
AB  - The X-ray structures of complexes of Thermoactinomyces vulgaris R-47 alpha
      amylase 1 (TVAI) with an inhibitor acarbose and an inactive mutant TVAI with
      malto-hexaose and malto-tridecaose have been determined at 2.6, 2.0 and 1.8A
      resolution, and the structures have been refined to R-factors of 0.185
      (R(free)=0.225), 0.184 (0.217) and 0.164 (0.200), respectively, with good
      chemical geometries. Acarbose binds to the catalytic site of TVAI, and
      interactions between acarbose and the enzyme are very similar to those found in
      other structure-solved alpha-amylase/acarbose complexes, supporting the proposed
      catalytic mechanism. Based on the structure of the TVAI/acarbose complex, the
      binding mode of pullulan containing alpha-(1,6) glucoside linkages could be
      deduced. Due to the structural difference caused by the replaced amino acid
      residue (Gln396 for Glu) in the catalytic site, malto-hexaose and malto
      tridecaose partially bind to the catalytic site, giving a mimic of the
      enzyme/product complex. Besides the catalytic site, four sugar-binding sites on
      the molecular surface are found in these X-ray structures. Two sugar-binding
      sites in domain N hold the oligosaccharides with a regular helical structure of
      amylose, which suggests that the domain N is a starch-binding domain acting as an
      anchor to starch in the catalytic reaction of the enzyme. An assay of hydrolyzing
      activity for the raw starches confirmed that TVAI can efficiently hydrolyze raw
      starch.

PMID- 14687577
TI  - The reactive-center loop of active PAI-1 is folded close to the protein core and
      can be partially inserted.
AB  - Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of plasminogen
      activators and plays an important role in many pathophysiological processes. Like
      other members of the serpin family, PAI-1 has a reactive center consisting of a
      mobile loop (RCL) with P1 and P1' residues acting as a "bait" for cognate
      protease. In contrast to the other serpins, PAI-1 loses activity by spontaneous
      conversion to an inactive latent form. This involves full insertion of the RCL
      into beta-sheet A. To search for molecular determinants that could be responsible
      for conversion of PAI-1 to the latent form, we studied the conformation of the
      RCL in active PAI-1 in solution. Intramolecular distance measurements by donor
      donor energy migration and probe quenching methods reveal that the RCL is located
      much closer to the core of PAI-1 than has been suggested by the recently resolved
      X-ray structures of stable PAI-1 mutants. Disulfide bonds can be formed in double
      cysteine mutants with substitutions at positions P11 or P13 of the RCL and
      neighboring residues in beta-sheet A. This suggests that the RCL may be
      preinserted up to residue P13 in active PAI-1, and possibly even to residue P11.
      We propose that the close proximity of the RCL to the protein core, and the
      ability of the loop to preinsert into beta-sheet A is a possible reason for PAI-1
      being able to convert spontaneously to its latent form.

PMID- 14687578
TI  - Mapping abeta amyloid fibril secondary structure using scanning proline
      mutagenesis.
AB  - Although the amyloid fibrils formed from the Alzheimer's disease amyloid peptide
      Abeta are rich in cross-beta sheet, the peptide likely also exhibits turn and
      unstructured regions when it becomes incorporated into amyloid. We generated a
      series of single-proline replacement mutants of Abeta(1-40) and determined the
      thermodynamic stabilities of amyloid fibrils formed from these mutants to
      characterize the susceptibility of different residue positions of the Abeta
      sequence to proline substitution. The results suggest that the Abeta peptide,
      when engaged in the amyloid fibril, folds into a conformation containing three
      highly structured segments, consisting of contiguous sequence elements 15-21, 24
      28, and 31-36, that are sensitive to proline replacement and likely to include
      the beta-sheet portions of the fibrils. Residues relatively insensitive to
      proline replacement fall into two groups: (a) residues 1-14 and 37-40 are likely
      to exist in relatively unstructured, flexible elements extruded from the beta
      sheet-rich amyloid core; (b) residues 22, 23, 29 and 30 are likely to occupy turn
      positions between these three structured elements. Although destabilized, fibrils
      formed from Abeta(1-40) proline mutants are very similar in structure to wild
      type fibrils, as indicated by hydrogen-deuterium exchange and other analysis.
      Interestingly, however, some proline mutations destabilize fibrils while at the
      same time increasing the number of amide protons protected from hydrogen
      exchange. This suggests that the stability of amyloid fibrils, rather than being
      driven exclusively by the formation of H-bonded beta-sheet, is achieved, as in
      globular proteins, through a balance of stabilizing and destabilizing forces. The
      proline scanning data are most compatible with a model for amyloid protofilament
      structure loosely resembling the parallel beta-helix folding motif, such that
      each Abeta(15-36) core region occupies a single layer of a prismatic, H-bonded
      stack of peptides.

PMID- 14687579
TI  - Identification of protein-protein interaction sites from docking energy
      landscapes.
AB  - Protein recognition is one of the most challenging and intriguing problems in
      structural biology. Despite all the available structural, sequence and
      biophysical information about protein-protein complexes, the physico-chemical
      patterns, if any, that make a protein surface likely to be involved in protein
      protein interactions, remain elusive. Here, we apply protein docking simulations
      and analysis of the interaction energy landscapes to identify protein-protein
      interaction sites. The new protocol for global docking based on multi-start
      global energy optimization of an all-atom model of the ligand, with detailed
      receptor potentials and atomic solvation parameters optimized in a training set
      of 24 complexes, explores the conformational space around the whole receptor
      without restrictions. The ensembles of the rigid-body docking solutions generated
      by the simulations were subsequently used to project the docking energy
      landscapes onto the protein surfaces. We found that highly populated low-energy
      regions consistently corresponded to actual binding sites. The procedure was
      validated on a test set of 21 known protein-protein complexes not used in the
      training set. As much as 81% of the predicted high-propensity patch residues were
      located correctly in the native interfaces. This approach can guide the design of
      mutations on the surfaces of proteins, provide geometrical details of a possible
      interaction, and help to annotate protein surfaces in structural proteomics.

PMID- 14687580
TI  - Implication of STAT1 and STAT3 transcription factors in the response to
      superantigens.
AB  - The activation of STAT1 and STAT3 in response to SEB was analyzed in spleen of
      Balb/c mice. The intraperitoneal injection of the superantigen SEB activated
      STAT1 and STAT3 in spleen. Activated STAT1 almost completely disappeared in 24 h
      even though activated STAT3 was present for more than 48 h after SEB injection.
      Cyclosporine A was able to block the initial STAT1 activation, but STAT3
      activation was only partially affected. SEB also increased the mRNA levels for
      STAT1, STAT3 and SOCS1. When a second injection with SEB was given 72 h after the
      first stimulus, STAT1 activation was much lower than that observed after the
      first stimulation with SEB and no increase in the STAT1 mRNA level was observed.
      Nevertheless, after this second injection, STAT3 was again activated without any
      significant interference from the first stimulus and the STAT3 and SOCS1 mRNA
      levels again increased. These data indicate that a first stimulation with
      superantigen re-programs cells so that they respond to a second stimulation in a
      different way. Understanding the mechanisms implicated in this re-programming is
      basic for designing therapeutic strategies in processes such as septic shock.

PMID- 14687581
TI  - Involvement of p38 and p42/44 MAP kinases and protein kinase C in the interferon
      gamma and interleukin-1alpha-induced phosphorylation of 85-kDa cytosolic
      phospholipase A(2) in primary human bronchial epithelial cells.
AB  - Interferon-gamma (IFN-gamma) and interleukin-1 (IL-1) play an important role in
      the modulation of acute and chronic airway inflammation. Both IFN-gamma and IL-1
      are known to increase the release of arachidonic acid (AA) from airway epithelial
      cells, suggesting that AA metabolites may mediate the cytokine-induced
      inflammation. This study was designed to examine the direct effect of IFN-gamma
      and IL-alpha on the phosphorylation of 85-kDa cytosolic phospholipase A(2)
      (cPLA(2)) and AA release in primary normal human bronchial epithelial (NHBE)
      cells. Treatment with IFN-gamma and IL-1alpha for 15 min induced a rapid increase
      of AA release from NHBE cells, which was blocked by the cPLA(2) inhibitor MAFP
      (p<0.05) but not by the sPLA(2) inhibitor LY311727 or iPLA(2) inhibitor HELSS.
      Immunoprecipitation and Western blot analysis showed that both IFN-gamma and IL
      1alpha induced a rapid phosphorylation of cPLA(2). The IFN-gamma and IL-1alpha
      induced cPLA(2) phosphorylation and AA release in the NHBE cells were inhibited
      by the p38 MAP kinase (MAPK) inhibitor SB203580, p42/44 MAPK inhibitor PD98059
      and protein kinase C (PKC) inhibitor bisindolylmaleimide I. These results
      demonstrate the involvement of p38 and p42/44 MAPKs as well as PKC in the IFN
      gamma and IL-1alpha-induced cPLA(2) phosphorylation and AA release in human
      airway epithelial cells.

PMID- 14687582
TI  - The effect of tumor necrosis factor-alpha on D-fructose intestinal transport in
      rabbits.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an important immunoregulatory cytokine
      involved in septic responses during bacterial infection. The aim of this study
      was to examine the effect of TNF-alpha on the transport of D-fructose across
      rabbit jejunum. A sepsis condition was evoked by intravenous administration of
      this cytokine and hematological and plasma parameters were analyzed and body
      temperature was recorded. D-Fructose transport was assayed in rabbit jejunum.
      Sugar absorption in TNF-alpha treated rabbits was lower than in control animals.
      TNF-alpha decreased both the mucosal-to-serosal transepithelial flux and the
      transport across brush border membrane vesicles of D-fructose. The number of D
      fructose transporters (GLUT5) was analyzed by Western blot in an attempt to
      explain this inhibition. TNF-alpha treated animals had lower levels of GLUT5,
      indicating a reduction in the expression of GLUT5 protein and therefore in
      transport capacity. The inhibition could also be related with the secretagogue
      effect of TNF-alpha on the gut since the intracellular tissue water was affected
      and the absence of chloride ion in the incubation medium partly removed the
      cytokine inhibition on sugar intestinal transport in treated rabbits. Finally, in
      terms of possible mediators involved in the TNF-alpha effect, nitric oxide and
      prostaglandins appeared to play a role in the inhibition of D-fructose intestinal
      uptake.

PMID- 14687583
TI  - Cytokine and chemokine expression profiles of maturing dendritic cells using
      multiprotein platform arrays.
AB  - Understanding the whole process of dendritic cell (DC) activation might help in
      the development of more efficient immunotherapeutic strategies for tumor
      patients. Part of this process is cytokine secretion, which has important effects
      on innate and adaptive immune response. Here, we cultured circulating monocytes
      for five days with interleukin-4 and GM-CSF followed by two-day culture with or
      without CD40 ligand and LPS to create a mature DC (mDC) and an immature DC (iDC)
      phenotype, respectively, characterized by differential expression of co
      stimulatory molecules (CD80, CD83). We then compared the cytokine expression
      profile of the mDC and iDC using two protein platform arrays. Twelve supernatants
      from mDC paired with 12 from iDC were compared. The mDC protein expression
      profile showed significant increases in 16 out of 34 factors tested, including
      TNFalpha, IL-10, IL-12, IFNgamma, MIP1alpha, MIP1beta, IL-8, MDC, RANTES, and IL
      6, which play a crucial role in the regulation of the innate immune response as
      well as the recruitment and activation of adaptive immune effectors.
      Interestingly, some of the cytokines expressed during maturation were also found
      in the gene expression profile identified in tumor metastases following IL-2
      therapy using cDNA arrays. This finding suggests a possible role for resident DC
      maturation as a mediator of systemic IL-2 effects. Most important, the array of
      cytokines secreted during DC maturation may be considered an important component
      during adoptive transfer. Further characterization of the kinetics and
      persistence of their secretion should be undertaken in the future.

PMID- 14687584
TI  - Orally administered bovine lactoferrin induces caspase-1 and interleukin-18 in
      the mouse intestinal mucosa: a possible explanation for inhibition of
      carcinogenesis and metastasis.
AB  - We have previously demonstrated that oral administration of bovine lactoferrin
      (bLF) markedly inhibits lung metastatic colony formation, and that this
      inhibition was possibly due to the activation of T and NK cells. Furthermore, we
      found that interleukin-18 (IL-18) is induced in epithelial cells of the small
      intestine by bLF. The present study was undertaken to confirm cytokine production
      in response to bLF and to assess the underlying mechanisms. Markedly elevated IL
      18 levels were found in the small intestine 1-3 h after a single administration
      of bLF, its pepsin hydrolysate (bLFH), or bTF. Importantly, while IL-18 was
      significantly increased after a regimen of seven daily administrations of bLF or
      bLFH, administration of bTF over the course of seven days had little or no
      effect. In addition to IL-18, a significant increase in caspase-1 activity and
      interferon-gamma (IFN-gamma) was found in the small intestine after
      administration of bLF. Similarly, in peritoneal macrophages, bLF markedly
      enhanced caspase-1 activity and IL-18 levels. Finally, a caspase-1 inhibitor
      significantly decreased bLF mediated induction of IL-18 in vitro. (bTF had no
      effect on either caspase-1 or IFN-gamma or on IL-18 in vitro.) These results
      demonstrate the possibility that elevation of caspase-1 activity by bLF and its
      hydrolysate may be important for production of mature IL-18 in vivo, and thus in
      potentiating the killing activity of T and NK cells against tumor cells.

PMID- 14687585
TI  - Disorders of body water homeostasis.
AB  - Disorders of body fluids are among the most commonly encountered problems in the
      practice of clinical medicine. This is in large part because many different
      disease states can potentially disrupt the finely balanced mechanisms that
      control the intake and output of water and solute. It therefore behoves
      clinicians treating such patients to have a good understanding of the
      pathophysiology, the differential diagnosis and the management of these
      disorders. Because body water is the primary determinant of the osmolality of the
      extracellular fluid, disorders of body water homeostasis can be divided into hypo
      osmolar disorders, in which there is an excess of body water relative to body
      solute, and hyperosmolar disorders, in which there is a deficiency of body water
      relative to body solute. The classical hyperosmolar disorder is diabetes
      insipidus (DI), and the classical hypo-osmolar disorder is the syndrome of
      inappropriate antidiuretic hormone secretion (SIADH). This chapter first reviews
      the regulatory mechanisms underlying water and sodium metabolism, the two major
      determinants of body fluid homeostasis. The major disorders of water metabolism
      causing hyperosmolality and hypo-osmolality, DI and SIADH, are then discussed in
      detail, including the pathogenesis, differential diagnosis and treatment of these
      disorders.

PMID- 14687586
TI  - Hereditary disorders of potassium homeostasis.
AB  - There has been a dramatic recent increase in the understanding of the renal
      epithelial transport systems with the identification, cloning and
      characterization of a large number of membrane transport proteins. The aim of
      this chapter is to integrate this body of knowledge with the understanding of the
      clinical disorders that accompany gain, loss or dysregulation of function of
      these transport systems. The specific focus is on the best-defined human clinical
      syndromes in which there are derangements in potassium (K(+)) homeostasis. The
      focus is on inherited syndromes, rather than on acquired syndromes due to tubular
      transport defects, and the therapeutic approaches address chronic derangements of
      K(+) homeostasis rather than acute interventions directed at life-threatening
      hyperkalaemia.

PMID- 14687587
TI  - Disorders of calcium homeostasis.
AB  - To ensure a multitude of essential cellular functions, the extracellular
      concentration of calcium is maintained within a narrow physiological range. This
      depends on integrated regulation of calcium fluxes with respect to the intestine,
      kidneys and bone. The precise regulation of serum calcium is controlled by
      calcium itself, through a calcium receptor and several hormones, the most
      important of which are parathyroid hormone and 1,25(OH)(2) vitamin D. This
      balance can be disturbed by mutations in the calcium-sensing receptor,
      inappropriately high or low levels of parathyroid hormone, resistance to
      parathyroid hormone effects, insufficient intake or production of 1,25(OH)(2)
      vitamin D and inactivation of the vitamin D receptor. Mineral homeostasis is
      moreover influenced by many other systemic factors (e.g. sex steroid, thyroid and
      glucocorticoid hormones) or humoral factors (e.g. cytokines and growth factors).
      A specific example is the major abnormalities of mineral homeostasis in case of
      malignancy by excessive production of parathyroid hormone-related peptide
      resulting in hypercalcaemia. Several new drugs have been developed based on
      factors in this axis, including calcimimetics, calcilytics, vitamin D analogues
      and parathyroid hormone-related peptide inhibitors.

PMID- 14687588
TI  - Disorders of phosphate metabolism--pathomechanisms and management of
      hypophosphataemic disorders.
AB  - Hypophosphataemia does not necessarily indicate phosphate (Pi) depletion. In
      acute emergencies such as septicaemia, alkalosis or re-feeding, hypophosphataemia
      may result from redistribution of Pi from the extracellular to the intracellular
      space. Hypophosphataemia from true Pi depletion gives rise to skeletal
      (osteomalacia) and extraskeletal (myopathy, cardiomyopathy) disorders. It is
      practically never the result of diminished nutritional intake. The most severe
      syndromes of Pi depletion result from diminished tubular Pi re-absorption and
      renal Pi wasting. In the differential diagnosis mainly four conditions have to be
      considered: (i) tumour-associated osteomalacia, (ii) X-linked hypophosphataemia
      (XLH), (iii) autosomal dominant hypophosphataemia, and (iv) hypercalcaemic renal
      phosphate wasting. Recent molecular insight has put fibroblast growth factor (FGF
      23) into the centre of pathophysiological considerations because of (i)
      overproduction (tumour-associated osteomalacia) or (ii) hypothetically,
      accumulation resulting from mutations causing resistance to processing or
      degradation (autosomal dominant hypophosphataemia) or (iii) loss-of-function of a
      protease (PHEX) interfering with FGF-23 breakdown (XLH). In oncogenic
      osteomalacia the treatment of choice is resection of the tumour. Recently,
      pharmacological treatment has also become possible, i.e. administration of
      octreotide. XLH and autosomal dominant hypophosphataemia must be managed by oral
      administration of phosphate and calcitriol. In patients with gastrointestinal
      intolerance to phosphate or with severely symptomatic bone disease, prolonged
      intravenous administration of Pi is necessary.

PMID- 14687589
TI  - Clinical acid-base pathophysiology: disorders of plasma anion gap.
AB  - The plasma anion gap is a frequently used parameter in the clinical diagnosis of
      a variety of conditions. The commonest application of the anion gap is to
      classify cases of metabolic acidosis into those that do and those that do not
      leave unmeasured anions in the plasma. While this algorithm is useful in
      streamlining the diagnostic process, it should not be used solely in this
      fashion. The anion gap measures the difference between the unmeasured anions and
      unmeasured cations and thus conveys much more information to the clinician than
      just quantifying anions of strong acids. In this chapter, the significance of the
      anion gap is emphasized and several examples are given to illustrate a more
      analytic approach to using the clinical anion gap; these include disorders of low
      anion gap, respiratory alkalosis and pyroglutamic acidosis.

PMID- 14687590
TI  - Cortisol and the renal handling of electrolytes: role in glucocorticoid-induced
      hypertension and bone disease.
AB  - Hypertension and osteoporosis are characteristic clinical features in patients
      with Cushing's syndrome or in those on glucocorticoid (GC) treatment. These two
      distinct complications of GC excess share one common denominator: an abnormal
      handling of cations, sodium (Na(+)) and calcium (Ca(2+)), either primarily or in
      part by the kidney tubule. The principal mechanism of GC-induced hypertension is
      overstimulation of the non-selective mineralocorticoid receptor (MR), resulting
      in renal Na(+) retention, volume expansion and finally to an increase in blood
      pressure. In mineralocorticoid target organs, such as the kidney, the MR is
      protected from GC occupation by the enzyme 11beta-hydroxysteroid dehydrogenase
      type 2 (11betaHSD2), a gate-keeping enzyme, which converts cortisol to receptor
      inactive cortisone. This enzyme allows aldosterone to be the physiological
      agonist of the MR despite significantly higher circulating levels of cortisol.
      Kinetic properties of 11betaHSD2 suggest that saturability of this enzyme can
      already be achieved at high-normal physiological plasma cortisol levels, thereby
      leading to ovestimualtion of the MR by cortisol in states of GC excess. The
      mechanisms of GC action on bone turnover are more complex. GCs increase bone
      resorption, inhibit bone formation and have an indirect action on bone by
      decreasing intestinal Ca(2+) absorption, but also inducing a sustained renal
      Ca(2+) excretion. The latter appears to be mediated through stimulation of the MR
      by GC. The prevention and treatment of GC-induced hypertension and osteoporosis
      include the use of the minimal effective dose of GC, some general measures, and
      the use of some specific drugs. Modulation of renal Na(+) and Ca(2+) excretion
      with some, but not all, diuretics represents an important specific (for
      hypertension) or supportive (for bone disease) therapeutic intervention.

PMID- 14687591
TI  - Primary aldosteronism.
AB  - Approaching the fiftieth year since its original description, primary
      aldosteronism is now thought to be the commonest potentially curable and
      specifically treatable form of hypertension. Correct identification of patients
      with primary aldosteronism requires that the effects of time of day, posture,
      dietary sodium intake, potassium levels and medications on levels of aldosterone
      and renin be carefully considered. Accurate elucidation of the subtype is
      essential for optimal treatment, and adrenal venous sampling is the only reliable
      means of differentiating aldosterone-producing adenoma from bilateral adrenal
      hyperplasia. With genetic testing already available for one inherited form,
      making more cumbersome biochemical testing for that subtype virtually obsolete
      and bringing about improvements in treatment approach, an intense search is
      underway for genetic mutations causing other, more common familial varieties of
      primary aldosteronism.

PMID- 14687592
TI  - Mechanisms of water and sodium retention in cirrhosis and the pathogenesis of
      ascites.
AB  - Patients with advanced cirrhosis and portal hypertension often show an abnormal
      regulation of extracellular fluid volume, resulting in the accumulation of fluid
      as ascites, pleural effusion or oedema. The mechanisms responsible for ascites
      formation include alterations in the splanchnic circulation as well as renal
      functional abnormalities that favour sodium and water retention. Renal
      abnormalities occur in the setting of a hyperdynamic state characterized by an
      increase cardiac output, a reduction in total vascular resistance and an
      activation of neurohormonal vasoactive systems. This circulatory dysfunction, due
      mainly to intense arterial vasodilation in the splanchnic circulation, is
      considered to be a primary feature in the pathogenesis of ascites. A major factor
      involved in the development of splanchnic arterial vasodilation is nitric oxide
      (NO), a potent vasodilator that is elevated in the splanchnic circulation of
      patients with cirrhosis. This event decreases effective arterial blood volume and
      leads to fluid accumulation and renal function abnormalities which are a
      consequence of the homeostatic activation of vasoconstrictor and antinatriuretic
      factors triggered to compensate for a relative arterial underfilling. The net
      effect is avid retention of sodium and water as well as renal vasoconstriction.
      The mechanisms of sodium and water retention and ascites formation in patients
      with cirrhosis are discussed in this review.

PMID- 14687593
TI  - Diagnosis and management of electrolyte emergencies.
AB  - Electrolyte and fluid imbalances are disorders frequently observed in critical
      care patients. In many instances patients are asymptomatic, but they may also
      present with neurological alterations, severe muscle weakness, nausea and
      vomiting or cardiovascular emergencies. Therefore, a pathophysiological
      understanding of these disorders is necessary for initiating an appropriate
      therapy. After a precise history-including drug prescriptions-has been obtained
      from the patient or his/her relatives, determination of the hydration status of
      the patient and measurement of acid-base status, plasma and urine osmolality and
      electrolytes are the first steps in the assessment of the disease. Once a
      diagnosis has been established, great attention has to be paid to the rate at
      which the disorder is corrected because this-if inappropriate-may cause more
      severe damage to the patient than the disease itself. This chapter addresses the
      initial diagnostic and therapeutic steps of the most common electrolyte
      emergencies.

PMID- 14687595
TI  - Biological rationale for endocrine therapy in breast cancer.
AB  - Oestrogens are heavily implicated in the risk to, and progression of, breast
      cancer. Therapeutic strategies targeted at the oestrogenic stimulus to the breast
      and hormone-sensitive breast cancers are extremely attractive measures both to
      prevent the disease and to treat established tumours. The present review outlines
      the biological rationale for such endocrine therapy and traces the evolution
      whereby irreversible surgical procedures have been replaced by potent and
      specific drugs. In particular, the development of the latest generation of agents
      which inhibit oestrogen biosynthesis (aromatase inhibitors) is considered by
      defining the central role of the aromatase enzyme, its regulation and
      contribution to circulating and tumour endogenous oestrogens. The nature of
      response and resistance which may be elicited following the use of endocrine
      therapy is also described as this may determine the optimal use of aromatase
      inhibitors and, more generally, anti-hormone therapy in the management of women
      at high risk to, or with, breast cancer.

PMID- 14687596
TI  - Oestrogen suppression--lessons from clinical studies.
AB  - In few, if any, areas of cancer research has "translational research" played a
      role such as the one it has played in the development of endocrine therapy. Thus,
      much of the understanding of the mechanisms of action of different therapies has
      been achieved by developing novel hypotheses based on clinical observations.
      Ovarian ablation was developed as an empirical therapy long before
      characterization of oestrogen disposition or detection of the oestrogen receptor.
      The first-generation aromatase inhibitor, aminoglutethimide, was implemented as a
      strategy to achieve a 'medical adrenalectomy' and was discovered as an aromatase
      inhibitor subsequent to clinical observations. Currently, observations such as
      the lack of cross-resistance between aromatase inhibitors and inactivators and
      the diverse effects from combined therapy using tamoxifen in concert with
      hormonal suppression in pre- and post-menopausals are provoking interesting
      questions for further research.

PMID- 14687597
TI  - The use of selective estrogen receptor modulators and selective estrogen receptor
      down-regulators in breast cancer.
AB  - Tamoxifen is one of the most effective treatments for breast cancer through its
      ability to antagonize estrogen-dependent growth by binding estrogen receptors
      (ERs) and inhibiting proliferation of breast epithelial cells. However, tamoxifen
      has estrogenic agonist effects in other tissues such as bone and endometrium due
      to liganded ER activating target genes in these different types of cell. Several
      novel anti-estrogen compounds have been developed which have a reduced agonist
      profile on breast and gynaecological tissues. These compounds offer the potential
      for enhanced efficacy and reduced toxicity compared with tamoxifen. In advanced
      breast cancer clinical data exist for two groups of agents: the selective
      estrogen receptor modulators (SERMs), further divided into "tamoxifen-like" (e.g.
      toremifene, droloxifene and idoxifene) and "fixed ring" compounds (e.g.
      raloxifene, arzoxifene and EM-800), and the selective estrogen receptor down
      regulators (SERDs; e.g. fulvestrant (ICI 182780), SR 16234 and ZK 191703) also
      termed "pure anti-estrogens". In phase II trials in tamoxifen-resistant
      metastatic breast cancer the SERMs show low objective response rates (range 0
      15%), suggesting cross resistance with tamoxifen. Randomized phase III trials for
      toremifene and idoxifene in over 1500 patients showed no significant difference
      compared with tamoxifen. Fewer clinical data exist for the "fixed ring" SERMs and
      it remains unclear whether any clinical advantage exists for the "fixed ring"
      SERMs over tamoxifen as first-line therapy. The main advantage for SERMs such as
      tamoxifen and raloxifene probably remains in early-stage disease (adjuvant
      therapy or prevention). Fulvestrant and the other SERDs have a high affinity for
      the estrogen receptor (ER) compared to tamoxifen, but none of its agonist
      activities. Of the SERDs, only fulvestrant has entered the clinic and this new
      agent is showing promising clinical activity in the treatment of advanced breast
      cancer. Recently published phase III studies have shown fulvestrant to be at
      least as effective as the third-generation aromatase inhibitor anastrozole in
      patients whose disease has relapsed or progressed on prior endocrine therapy.
      Surprisingly, however, in a phase III trial versus tamoxifen for the first-line
      therapy of advanced breast cancer fulvestrant did not attain the requirements for
      equivalence to tamoxifen, and in terms of time-to-treatment failure was inferior
      (5.9 versus 7.8 months for fulvestrant and tamoxifen, respectively; P=0.029).
      Future clinical studies will evaluate fulvestrant in the neoadjuvant setting
      together with its optimal sequencing in relation to tamoxifen and other endocrine
      therapies in advanced disease.

PMID- 14687599
TI  - Adjuvant endocrine therapy.
AB  - Endocrine therapy remains a cornerstone of systemic therapy for breast cancer
      even though it was first introduced more than a century ago. In the past three
      decades a large number of randomized trials involving several tens of thousands
      of patients have been performed to determine the role of endocrine therapy in the
      adjuvant setting. The results of these studies indicate that hormonal therapy
      should be considered the standard adjuvant systemic treatment for the majority of
      patients with invasive breast cancer irrespective of age, menopausal status or
      tumour stage. This chapter aims to describe the "state of the art" relative to
      the use of adjuvant endocrine therapy with special focus on a number of salient
      issues, including: (i) the role of ovarian ablation and luteinising hormone
      releasing hormone (LHRH) analogues among pre-menopausal patients; (ii) optimal
      duration of tamoxifen; (iii) adjuvant therapy with third-generation, selective
      aromatase inhibitors; (iv) predictive biomarkers; (v) side-effects; (vi)
      combination endocrine therapy; (vii) future development of endocrine therapy.

PMID- 14687598
TI  - The insulin-like growth factor system in advanced breast cancer.
AB  - Despite improvements in therapy, the prognosis for advanced breast cancer is poor
      and a search for new treatment targets and key regulators of tumour growth is
      warranted. Extensive data are available on the importance of the insulin-like
      growth factor (IGF) system in growth regulation of breast cancer cell lines in
      vitro, indicating that the IGF-I receptor (IGF-IR), IGF-I (and IGF-II) function
      as survival factors, while IGF binding protein (IGFBP)-3 may act as a growth
      inhibitor. There is a tight link between the growth regulatory pathways of IGFs
      and oestrogens in oestrogen-receptor(OR)-positive breast cancer cells. In vivo
      studies indicate a role of IGF-I and IGF-IR in breast cancer development.
      However, the importance of the IGF system in metastatic and highly aggressive
      breast tumours in vivo is not clear, and therapeutic strategies designed to
      interrupt IGF signalling have not yet proved to be an effective treatment
      modality in patients with metastatic breast cancer.

PMID- 14687600
TI  - Endocrine prevention of breast cancer using selective oestrogen receptor
      modulators (SORMs).
AB  - Breast cancer remains the most common malignancy in women worldwide. Oestrogen
      levels appear to be associated with an increased risk for the development of
      breast cancer. The Early Breast Cancer Trialists' Cooperative Group reported in a
      1998 meta-analysis of 37000 breast cancer patients in 55 randomized adjuvant
      trials that tamoxifen, a selective oestrogen receptor modulator, reduced the
      incidence of contralateral breast cancers by 47% at 5 years. Tamoxifen has been
      shown in numerous prevention studies to decrease the incidence of breast cancer
      in high-risk women. Overall, the tamoxifen prevention trials showed a 38%
      reduction in the incidence of breast cancer (95% CI 28-46; P<0.0001). In the
      largest risk-reduction trial, the Breast Cancer Prevention Trial conducted by the
      National Surgical Adjuvant Breast and Bowel Project, tamoxifen reduced the risk
      of invasive breast cancer by 49% (two-sided P<0.00001), and non-invasive breast
      cancer by 50% (P<0.002). The occurrence of oestrogen receptor-(OR)-positive
      tumours decreased by 69%. Tamoxifen reduces the risk of developing oestrogen
      receptor-positive tumours, but OR-negative tumours are not affected. Rare but
      life-threatening side-effects of tamoxifen include endometrial carcinoma,
      thromboembolic events and cerebrovascular events. Less serious side-effects
      include cataracts, vasomotor instability, nausea and vaginal discharge.
      Raloxifene, a second-generation selective oestrogen receptor modulator, is
      approved for treatment of osteoporosis in post-menopausal women in the USA but it
      is not currently approved for breast cancer prevention outside of a clinical
      trial. Prevention studies involving raloxifene and aromatase inhibitors are
      currently being conducted.

PMID- 14687601
TI  - Aromatase inhibitors for chemoprevention.
AB  - Pre-clinical, molecular and epidemiological evidence supports a role for estrogen
      in both the initiation and promotion of breast cancer. Antagonizing estrogen has
      therefore been proposed as one way of reducing risk. Tamoxifen, which competes
      with estrogen at the estrogen receptor, has been shown in four phase III clinical
      trials to reduce tumour occurrence substantially. Aromatase inhibitors are
      superior to tamoxifen in terms of both efficacy and toxicity in advanced disease
      and in the neoadjuvant and adjuvant setting. Exemestane may be distinct because
      its steroidal structure potentially protects bone and lipid metabolism from
      estrogen ablation. Phase three trials are ongoing to test the efficacy of the
      inhibitors, including the IBIS 2 trial which randomizes anastrozole against
      placebo and the NCIC CTG MAP.3 study of exemestane with or without celecoxib
      against placebo. The efficacy and toxicity results of these studies, and the
      identification of risk profiles from them, are awaited with interest.

PMID- 14687603
TI  - Inhibition of cytokines expression in human microglia infected by virulent and
      non-virulent mycobacteria.
AB  - The pathogenesis of tuberculosis (TBC) meningitis is still unknown. As shown by
      previous studies, human microglia can be the target of mycobacteria, but no data
      are available about their cellular response to infection. Consequently, we
      studied the expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1
      (IL-1) and IL-10 in human microglia pure cultures infected with the two variants
      of Mycobacterium avium (domed-opaque (SmD) and transparent (SmT)) and with
      Mycobacterium tuberculosis. Results showed that microglia was productively
      infected by mycobacteria which could grow inside the cells. Mycobacteria
      internalization was more rapid for M. avium, but M. tuberculosis infection turned
      out to be more efficient due to the incorporation of densely packed bacteria. TNF
      alpha expression was not affected by M. avium, whereas an increase followed by a
      decrease was observed in M. tuberculosis. Both IL-1 and IL-10 cytokine expression
      was rapidly inhibited by infection with the more virulent bacteria, whereas the
      non-pathogenic one had almost no effect. Also, the expression of the co
      stimulatory molecule CD137, a member of tumor necrosis factor receptor family,
      was affected by infection with virulent mycobacteria. Our results show that
      microglia response to mycobacterial infection is modulated in correlation with
      virulence, mainly toward inhibition of inflammatory response. This observation
      might be one of the mechanisms by which non-pathogenic mycobacteria are quickly
      eliminated, explaining one of the bases of virulence.

PMID- 14687604
TI  - N-Propargyl-1 (R)-aminoindan, rasagiline, increases glial cell line-derived
      neurotrophic factor (GDNF) in neuroblastoma SH-SY5Y cells through activation of
      NF-kappaB transcription factor.
AB  - N-Propargyl-l(R)-aminoindan, rasagiline, an anti-Parkinson drug, was found to
      increase the protein and mRNA levels of glial cell line-derived neurotrophic
      factor (GDNF) in human neuroblastoma SH-SY5Y cells, whereas an analogue without a
      propargyl residue, aminoindan, did not. GDNF is known to protect dopaminergic
      neurons in animal and cellular models of Parkinson's disease, and the supplement
      has been tried for the treatment of degenerating dopamine neurons in Parkinsonian
      patients. In this paper, intracellular mechanism underlying the induction of GDNF
      was studied. Rasagiline induced phosphorylation of inhibitory subunit (IkappaB)
      of nuclear factor-kappaB (NF-kappaB), and translocation of active p65 subunit
      from cytoplasm into nuclei. Activation of NF-kappaB was also quantitatively
      determined by NF-kappaB p65 transcription assay. Sulfasalazine, an inhibitor of
      IkappaB kinase, suppressed the activation of NF-kappaB and the increase of GDNF
      by rasagiline simultaneously, further indicating the involvement of the IkappaB
      kinase-NF-kappaB pathway. The results on the activation of the transcription
      factor by rasagiline are discussed in relation to its possible application as a
      neuroprotective drug to halt declining of neurons in neurodegenerative disorders,
      such as Parkinson's and Alzheimer's diseases.

PMID- 14687605
TI  - The neuroprotective effects of estrogen in SK-N-SH neuroblastoma cell cultures.
AB  - Estrogen has been considered to be a neuroprotectant and a neuromodulator in many
      neuronal cell lines and tissue preparations. The protective effects of estrogen
      may be mediated through classical estrogen receptors (ERs), or may be due to its
      anti-oxidant properties which are independent of receptors. The current studies
      show that 17beta-estradiol (E2) is neuroprotective against beta-amyloid protein
      25-35 (Abeta)-, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-, high
      density culture condition-, and serum deprivation-induced neuronal death in SK-N
      SH human neuroblastoma cells. SK-N-SH cells express ERbeta, but not ERalpha, as
      detected by Western blot analysis. Among all the insults, MPTP, high density
      culture and serum deprivation induce apoptotic cell death in this cell system as
      detected by ELISA determination of mono/oligonucleosomes and DNA laddering, while
      Abeta induces necrotic cell death. The protective effects of E2 are abolished by
      the addition of tamoxifen and ICI 182,780 in the MPTP treated cells, but not in
      the other models, suggesting that the effect of E2 in the MPTP model is probably
      associated with activation of ERbeta. The addition of ICI 182,780 shows a
      mitogenic effect in SK-N-SH cells in the presence of E2 in control culture or in
      the Abeta treated groups. Also, ICI 182,780 induced expression of ERalpha.
      Collectively, the current studies suggest that E2 is neuroprotective in apoptotic
      and necrotic death induced by multiple insults in SK-N-SH human neuroblastoma
      cells. Involvement of ER is insult type dependent. ICI 182,780 is able to
      influence the expression of ERs, probably through upregulation of ERalpha when
      ERbeta is totally antagonized.

PMID- 14687606
TI  - Immunohistochemical detection by immersion fixation with Carnoy solution of
      particular non-N-methyl-D-aspartate receptor subunits in murine hippocampus.
AB  - Immunoblotting analysis revealed heterologous distribution profiles of the non-N
      methyl-D-aspartate (NMDA) receptor subunits, GluR1, GluR2 and GluR6, in membrane
      fractions prepared from murine discrete brain structures including hippocampus.
      In coronal sections fixed with paraformaldehyde (PA) solution after dissection
      from mice perfused with 4% PA, however, no marked immunoreactivity was detected
      to GluR6 subunit in any hippocampal subregions, with high immunoreactivities to
      both GluR1 and GluR2 subunits in the strata oriens, radiatum and lacunosum
      moleculare of the CA1 and CA3 subfields and the stratum moleculare of the dentate
      gyrus in hippocampus. In coronal, sagittal and horizontal sections fixed with
      Carnoy solution after dissection from animals decapitated, by contrast, high
      immunoreactivity was additionally detected to GluR6 subunit in the stratum
      lucidum of hippocampus. The systemic administration of kainate not only resulted
      in marked neuronal losses along the CA1-CA4 pyramidal layers 1 week later, but
      also led to significant decreases in immunoreactivities to GluR1, GluR2 and GluR6
      subunits in the CA1 and CA3 subfields on brain coronal sections prepared by
      immersion fixation with Carnoy solution. These results suggest that immersion
      fixation with Carnoy solution may be suitable and appropriate for reproducible
      and quantitative immunohistochemical detection of particular non-NMDA receptor
      subunits in murine hippocampus.

PMID- 14687607
TI  - Guanine derivatives modulate L-glutamate uptake into rat brain synaptic vesicles.
AB  - Glutamate uptake into synaptic vesicles is driven by a proton electrochemical
      gradient generated by a vacuolar H(+)-ATPase and stimulated by physiological
      concentrations of chloride. This uptake plays an important role in glutamatergic
      transmission. We show here that vesicular glutamate uptake is selectively
      inhibited by guanine derivatives, in a time- and concentration-dependent manner.
      Guanosine, GMP, GDP, guanosine-5'-O-2-thiodiphosphate, GTP, or 5'
      guanylylimidodiphosphate (GppNHp) inhibited glutamate uptake in 1.5 and 3 min
      incubations, however, when incubating for 10 min, only GTP or GppNHp displayed
      such inhibition. By increasing ATP concentrations, the inhibitory effect of GTP
      was no longer observed, but GppNHp still inhibited glutamate uptake. In the
      absence of ATP, vesicular ATPase can hydrolyze GTP in order to drive glutamate
      uptake. However, 5mM GppNHp inhibited ATP hydrolysis by synaptic vesicle
      preparations. GTP or GppNHp decreased the proton electrochemical gradient,
      whereas the other guanine derivatives did not. Glutamate saturation curves were
      assayed in order to evaluate the specificity of inhibition of the vesicular
      glutamate carrier by the guanine derivatives. The maximum velocity of the initial
      rate of glutamate uptake was decreased by all guanine derivatives. These results
      indicate that, although GppNHp can inhibit ATPase activity, guanine derivatives
      are more likely to be acting through interaction with vesicular glutamate
      carrier.

PMID- 14687608
TI  - Evaluation of three quinoline-carboxamide derivatives as potential radioligands
      for the in vivo pet imaging of neurodegeneration.
AB  - The peripheral-type benzodiazepine receptors (PBRs) are only minimally expressed
      in normal brain parenchyma, where they are primarily localized in glial cells.
      Their basal expression rises in different neurodegenerative disorders, due to the
      presence of infiltrating inflammatory cells and activated microglia.
      [11C]PK11195, a selective PBR antagonist, has been used for the in vivo PET
      monitoring of neurodegeneration in clinical observations. We recently developed
      and labeled with carbon-11 three new carboxamide derivatives: [11C]VC193M,
      [11C]VC195 and [11C]VC198M. Aim of this study was to evaluate these ligands for
      the in vivo measuring of PBRs expression in neurodegenerations and compare their
      kinetic behavior with that of the reference tracer [11C]PK11195. Radioligands
      were evaluated in a preclinical model of Huntington's disease consisting in the
      monolateral striatal injection of quinolinic acid (QA). Activated microglia and
      astrocytic gliosis was present only within the affected striatum. A concomitant
      increase in radioactivity accumulation was observed for all the tracers examined
      (P<0.01). Among the new compounds, [11C]VC195 showed higher levels of
      lesioned/unlesioned striatum ratios (3.28+/-0.44), in comparison with [11C]VC193M
      and [11C]VC198M (2.69+/-0.53 and 1.52+/-0.36, respectively), but slightly
      inferior to that observed for [11C]PK11195 (3.76+/-1.41).In conclusion, the
      results of the study indicate that [11C]VC195 is a promising candidate for in
      vivo PET monitoring of neurodegenerative processes but its in vivo behavior
      overlap that of [11C]PK11195.

PMID- 14687610
TI  - Expression of lysosomal protective protein/cathepsin A in a stably transformed
      human neuroblastoma cell line during bi-directional differentiation into neuronal
      and Schwannian cells.
AB  - Human neuroblastoma GOTO cell lines were established that stably express
      recombinant human lysosomal protective protein/cathepsin A (PPCA) cDNA by
      transfection. Intracellular cathepsin A (acid serine carboxypeptidase) activity
      increased four-fold compared with in those of the parent and mock-transfected
      cell lines. The immunoreactive 54 kDa precursor/zymogen and mature 32/20 kDa two
      chain forms were produced in the cells. The amount of the latter form expressed
      in the GOTO cells was significantly larger than those in the PPCA-overexpressing
      CHO cell lines previously established. The intracellular proteins showed a
      typical lysosomal granular distribution and the glycosylated 54 kDa precursor was
      secreted into the culture medium without the addition of an alkalizing agent. The
      PPCA-overexpressing cell lines also retained the ability to differentiate bi
      directionally as well as the parent cells; into neuronal cells on induction by
      dibutyryl cAMP in serum-free medium and into Schwannian cells on induction by
      bromodeoxyuridine. During the course of differentiation into neuronal and
      Schwannian cells, the intracellular cathepsin A activity further increased two
      and five times, respectively, which was associated with an increase in the
      expression of the 32/20 kDa two-chain form. The glycosylated precursor proteins
      were taken up via the mannose 6-phosphate receptors, and the cathepsin A, alpha
      neuraminidase and beta-galactosidase (beta-Gal) activities deficient in the
      fibroblasts derived from a patient with PPCA deficiency (galactosialidosis) were
      restored. These results suggest that the bi-directional differentiation of GOTO
      cell lines stably expressing the recombinant human PPCA gene could be a model
      system for analyzing the functions of PPCA in peripheral neuronal cells and
      Schwannian cells as well as the recombinant PPCA could be a useful source for
      enzyme replacement therapy (ERT) for galactosialidosis patients.

PMID- 14687609
TI  - Participation of PI3K and ERK1/2 pathways are required for human brain vascular
      smooth muscle cell migration.
AB  - Human brain vascular smooth muscle cell (HBVSMC) migration contributes to
      angiogenesis and several pathological processes in the brain. However, the
      molecular mechanism of angiogenesis, in which smooth muscle cell contributes,
      remains unclear. Our study investigates the role of vascular endothelial growth
      factor (VEGF) in the HBVSMC migration and elucidates the chemotactic signaling
      pathway mediating this action. We used the in vitro 'scratch' wound method to
      detect the HBVSMC migration. VEGF(165) (1-40ng/ml) induced the HBVSMC migration
      in a dose-dependent manner (P<0.05). VEGF(165) does not induce HBVSMC
      proliferation. Wortmannin, a specific phosphatidylinositol 3-kinase (PI3K)
      inhibitor, significantly inhibited serine/threonine kinase Akt/protein kinase B
      (PKB) phosphorylation and reduced HBVSMC migration into the wound edge following
      VEGF(165) stimulation (P<0.05). PD98059, an extracellular signal-regulated kinase
      1/2 (ERK1/2) inhibitor, also significantly inhibited ERK1/2 phosphorylation and
      reduced the numbers of SMC migration. Parallel distance measurement showed that
      VEGF(165) induced HBVSMC migration significantly reduced due to inhibition of
      PI3K or ERK1/2 phosphorylation (P<0.05). Our results demonstrate that VEGF(165)
      could induce HBVSMC migration but not proliferation in vitro. Inhibiting Akt/PKB
      or ERK1/2 phosphorylation could reduce VEGF(165) induced HBVSMC migration. We
      provide the first evidence that activation of PI3K or ERK1/2 pathways are a
      crucial event in VEGF(165) mediated signal transduction leading to HBVSMC
      migration.

PMID- 14687611
TI  - Involvement of histone phosphorylation in apoptosis of human astrocytes after
      exposure to saline solution.
AB  - We have previously found using inhibitors of protein phosphatase that
      phosphorylation of histones may be involved in thymocyte apoptosis. In this
      study, we examined whether histone modification occurs in astrocyte apoptosis
      induced by a pathological condition in the absence of drug. Incubation of
      cultured human astrocytes with growth medium for 24 h after exposure to saline
      solution for 30 min induced an increase in terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL)-positive cells and nuclear condensation,
      biochemical and morphological hallmarks of apoptotic cell death. Acetic acid-urea
      Triton X-100 (AUT) gel electrophoresis of the nuclear histone fraction and N
      terminal peptide analysis showed that the treatment with saline solution caused
      rapid changes in phosphorylation of H2A subfamilies, but not in histone
      acetylation. The phosphorylation of the two subtypes increased markedly, whereas
      the phosphorylation of one subtype decreased. In contrast, exposure to ACF-95, an
      artificial cerebrospinal fluid (CSF), was associated with little induction of
      apoptotic cell death and induced less changes in histone phosphorylation. These
      results support the previous idea that chemical modification of histones is
      involved in the DNA fragmentation in astrocytes undergoing apoptosis.

PMID- 14687612
TI  - Tyrosine kinases in AML: where do they fit in?

PMID- 14687613
TI  - Comparative gene expression profile of p185(Bcr-Abl) versus p210(Bcr-Abl)
      expressing cells.

PMID- 14687614
TI  - The angiogenic status of B-CLL B cells: role of the VEGF receptors.

PMID- 14687615
TI  - Treatment of systemic mast cell disease: beyond interferon.

PMID- 14687616
TI  - A novel EBV-negative natural killer cell line.

PMID- 14687617
TI  - T-cell-rich B-cell lymphoma: a clinicopathologic study of 21 cases and comparison
      with 43 cases of diffuse large B-cell lymphoma.
AB  - Clinicopathologic features of 21 patients with T-cell-rich B-cell lymphoma
      (TCRBCL) were reviewed and compared to 43 patients with diffuse large B-cell
      lymphoma (DLBCL) to determine if there were distinguishing clinical
      characteristics and differences in response or survival to CHOP therapy. For the
      diagnosis of TCRBCL, the current WHO criteria was used. In all of our cases, the
      majority of cells are non-neoplastic T cells and <10% large neoplastic B cells
      are present. The initial pathologic diagnosis was nodular lymphocyte predominant
      Hodgkin's lymphoma (NLPHL) in two cases. Patients with TCRBCL were significantly
      younger (median: 46 years) and had a significantly higher incidence of B symptoms
      (62%), hepatomegaly (33%) and marrow infiltration (33%) at presentation when
      compared to DLBCL (P<0.03). The CR rate after treatment was 48% for TCRBCL
      patients versus 79% for the DLBCL (P<0.003). Although the CR rates in between the
      two groups are significant, the difference in 3 years survival rates in each CR
      groups was insignificant (80% versus 77%). The overall survival time in the two
      groups was 17 months. Event-free survival time in TCRBCL was 12 months, compared
      with 17 months in the DLBCL (P>0.05). The frequency of patients with TCRBCL
      achieving CR was 52.6% whereas that of patients with DLBCL was 79% (P<0.003). The
      TCRBCL 3 years event-free survival 48% and overall survival 64% were 63 and 72%
      for DLBCL, respectively.

PMID- 14687618
TI  - The soluble form of CD83 is present at elevated levels in a number of
      hematological malignancies.
AB  - Recombinant forms of soluble CD83 (sCD83) inhibit anti-tumor responses. In this
      analysis of circulating sCD83 levels we report that although >95% of acute
      myeloid leukemia (AML) and multiple myeloma (MM) patients have normal or only
      weakly elevated sCD83 levels, 20% of chronic lymphocytic leukemia (CLL) and 5/7
      mantle cell lymphoma (MCL) patients have significantly elevated levels (>1
      ng/ml). Isolated CLL cells both weakly expressed membrane CD83 (mCD83), and
      released sCD83 during in vitro culture. We conclude that malignant cells are a
      potential source of sCD83 and that it may have functional and/or prognostic
      significance in hematological malignancies, particularly CLL and MCL.

PMID- 14687619
TI  - All three receptors for vascular endothelial growth factor (VEGF) are expressed
      on B-chronic lymphocytic leukemia (CLL) cells.
AB  - B-chronic lymphocytic leukemia (B-CLL) cells have a long survival owing to an
      alteration in the normal pathways of apoptosis. CLL cells have been found to
      produce and secrete vascular endothelial growth factor (VEGF). In addition to its
      major role in angiogenesis, VEGF affects cell survival by interfering with
      apoptosis. The aim of the present study was to investigate the expression of the
      VEGF receptors VEGFR-1, VEGFR-2, and VEGFR-3 on B-CLL cells, singly and combined.
      B-CLL cells were isolated from peripheral blood drawn from patients with CLL.
      Total VEGF receptor, examined in 13 samples by flow cytometry was present in all
      cases with mean CD19+/VEGF+ expression of 76% (range 52-92%). Specific receptor
      expression, examined in 27 samples by immunocytochemical methods, was positive
      for VEGFR-1 in all 27 patients and for VEGFR-2 and VEGFR-3 in 26 (96%). These
      findings suggest that the VEGF transduction pathway may be very active in CLL
      cells, and both its paracrine and autocrine pathways may contribute to their
      enhanced survival.

PMID- 14687620
TI  - Response to therapy with interferon alpha-2b and prednisolone in aggressive
      systemic mastocytosis: report of five cases and review of the literature.
AB  - Aggressive systemic mastocytosis (ASM) is a hematopoietic neoplasm characterized
      by infiltration of visceral organs by neoplastic mast cells (MCs) with
      consecutive organopathy and respective clinical and laboratory findings (so
      called C-Findings). Whereas, it is generally appreciated that patients with ASM
      are candidates for pharmacological intervention, no ideal drug or drug
      combination have been identified yet. One drug proposed to work in ASM is
      interferon alpha-2b (IFN-alpha2b). However, little is known so far about the
      quality of responses to IFN-alpha2b and actual response rates. We here report on
      five ASM patients treated with either a combination of IFN-alpha2b (3x3 million
      units per week) and prednisolone (n=4), or IFN-alpha2b alone (n=1). During
      therapy, two of the five patients showed a major response defined by complete
      resolution of C-Finding(s), one a partial response (partial regression of C
      Findings), and one a stable disease (no changes in C-Findings). In one patient,
      progression to mast cell leukemia was seen after 3 months. In contrast to the
      other patients, this patient exhibited >10% MCs in his bone marrow (bm) smear at
      first presentation. In summary, our data confirm beneficial effects of IFN
      alpha2b (plus prednisolone) for a group of patients with ASM, whereas patients
      with mast cell leukemia may require more aggressive therapy. Prospective trials
      with more patients are now required to further document these drug effects and to
      better define subgroups of patients with ASM who show good and long-lasting
      responses to IFN-alpha2b.

PMID- 14687621
TI  - Interleukin-18 in multiple myeloma patients: serum levels in relation to response
      to treatment and survival.
AB  - Interleukin-18 (IL-18) plays a role in the host's response to tumours and
      angiogenesis. We determined serum levels of IL-18, vascular endothelial growth
      factor (VEGF), angiogenin (ANG), tumor necrosis factor (TNF-alpha) and CRP in 65
      newly diagnosed myeloma patients. IL-18, VEGF, angiogenin, TNF-alpha and CRP were
      significantly higher at stage III in comparison to stages II and I. These
      cytokines (measured in 27 patients) significantly decreased after treatment. In
      survival analysis, higher levels of IL-18 were associated with a poorer
      prognosis. We conclude that increased serum IL-18 in myeloma patients correlates
      with advanced disease, increased levels of angiogenic cytokines and worse
      survival.

PMID- 14687622
TI  - T cell receptor gamma (TCRG) gene rearrangements in Brazilian children with acute
      lymphoblastic leukemia: analysis and implications for the study of minimal
      residual disease.
AB  - The high frequency of T cell receptor gamma (TCRG) gene rearrangements in both B
      lineage and T cell acute lymphoblastic leukemia (ALL), its easy detection and the
      lower incidence of oligoclonality make this gene one of the main target for the
      detection of minimal residual disease by PCR in childhood ALL. We analyzed the
      frequency and type of TCRG rearrangements in DNA samples obtained from the bone
      marrow of 102 Brazilian children at diagnosis using PCR and automatic sequencing.
      TCRG rearrangements were found in 69% of patients with B-lineage ALL and in 94%
      of patients with T cell ALL. In contrast to other studies, rearrangements
      involving the Vgamma9 segment reported to be uncommon were the most frequent both
      in B-lineage and T cell ALL and involved 49/109 (45%) of the rearranged alleles.
      This fact should be considered when standardizing consensus primers for the study
      of minimal residual disease in different populations.

PMID- 14687623
TI  - A new human natural killer leukemia cell line, IMC-1. A complex chromosomal
      rearrangement defined by spectral karyotyping: functional and cytogenetic
      characterization.
AB  - A new human IL-2 dependent leukemic cell line with a natural killer (NK) cell
      phenotype, IMC-1, was established from an adult patient with aggressive NK cell
      leukemia. The IMC-1 cell line expresses the CD56, CD2, CD11a, CD38 and HLA-DR
      cell surface antigens, whereas the CD16 and CD8 antigens expressed on the primary
      leukemic blasts from which the cell line was derived were lost after 7 and 28
      weeks of culture, respectively. The IMC-1 cell line displays functional NK
      cytotoxicity and lyses target cells in a non-MHC restricted, antibody-independent
      manner with equal or superior efficiency to freshly isolated NK cells.
      Cytogenetic analysis at presentation and after 55 weeks in culture revealed
      complex structural and numerical abnormalities, defined by classic G-banding and
      by spectral karyotyping (SKY). Three apparently intact copies of chromosome 8
      occurred in the diagnostic bone marrow specimen; the cell line also contains
      three copies of chromosome 8 but each was structurally altered. The development
      and detailed characterization of this new NK leukemic cell line will facilitate
      biologic and functional studies of NK cells and chromosomal aberrations
      potentially important in leukemic transformation.

PMID- 14687625
TI  - An in vivo propagated human acute myeloid leukemia expressing ABCA3.
AB  - Analyzing the regenerative compartment in the blast cell population of patients
      with acute myeloid leukemia (AML) may yield important insights into the
      mechanisms of disease progression. Here we present findings with a human AML cell
      line (AML-SP1), initiated from leukemic precursor cells and consecutively
      propagated by serial xenotransplantation in vivo. AML-SP1 maintained the
      characteristics of a human AML, consistently exhibiting a small leukemic side
      population (SP) of blast cells with high Hoechst 33342 exclusion. In the AML-SP1
      line, an increased expression of the ABC transporters MDR1, MRP, ABCG2 and ABCA3
      was found in the SP cells. The detection of ABCA3 in leukemic progenitor cells
      merits further investigation with regard to intracellular drug transport in AML
      blast cells. In vivo propagation of leukemias, such as AML-SP1 is a model system
      of maintaining the populational heterogeneity of AML disease, especially the
      unique characteristics of leukemic SP cells.

PMID- 14687624
TI  - Elevated expression of a subset of interferon inducible genes in primary bone
      marrow cells expressing p185 Bcr-Abl versus p210 Bcr-Abl by DNA microarray
      analysis.
AB  - p185 Bcr-Abl has a more aggressive biological/clinical leukemia phenotype than
      p210 Bcr-Abl. In this study, we examined differential gene expression using
      microarrays to determine if upregulation or downregulation of specific genes may
      explain the distinct phenotypes produced by the two Bcr-Abl forms. RNA was
      collected from mouse bone marrow mononuclear cells expressing equivalent levels
      of p185 or p210, and the RNAs were subjected to microarray analysis. Significant
      differences in gene expression were observed on hierarchical clustering. A group
      of interferon-gamma-inducible genes, including those encoding a family of 47 kDa
      GTPases, were significantly increased in p185 versus p210. This family of GTPases
      has previously been implicated in interferon-gamma-induced resistance against
      intracellular pathogens, however their exact cellular functions are unknown. Our
      data suggest that their increased expression may contribute to the
      biological/clinical phenotype associated with p185.

PMID- 14687626
TI  - Inhibitory effects of phaseolotoxin on proliferation of leukemia cells HL-60, K
      562 and L1210 and pancreatic cells RIN-m5F.
AB  - Phaseolotoxin (PT) is a non-host specific phytotoxin produced by the plant
      pathogenic bacterium Pseudomonas syringae (P.s.) pv. phaseolicola. In the present
      study, the inhibitory effect of PT on the proliferation of leukemia cells was
      studied. After 4 days of treatment, PT decreased cell growth of leukemia cell
      lines HL-60, K-562 and L1210 in a dose-dependent manner. In addition, PT also
      reduced cell growth of the insulinoma pancreatic cell line RIN-m5F. IC50 values
      were 2.1 +/- 1.0 microM (HL-60), 13.3 +/- 3.7 microM (K-562), 2.5 +/- 0.4 microM
      (L1210) and 5.5 +/- 0.3 microM (RIN-m5F). Although the exact mechanism by which
      PT inhibits cell growth in these cells is currently not known, we present first
      evidence that PT may in part be active via inhibition of ornithine decarboxylase
      (ODC). Based on our findings, PT presents a lead compound with potential for
      further development into a new anti-cancer agent.

PMID- 14687627
TI  - Phenotypical alterations induced by glucocorticoids resistance in RPMI 8226 human
      myeloma cells.
AB  - Resistance to glucocorticoids (GCs) frequently appears during treatment of
      hematological malignancies. This study investigates the phenotypical alterations
      observed in human myeloma cell sublines resistant to glucocorticoids. Using the
      RPMI8226 cell line, the cytotoxic efficiencies of four glucocorticoids, and the
      phenotypes of isolated resistant sublines were analyzed. Methyl-prednisolone and
      dexamethasone exhibited the higher toxic effects on RPMI8226 cells. All
      corticoids were able to induce drug-resistance. Resistant sublines showed an
      increased expression of the alpha-isoform of the glucocorticoid receptors (GRs),
      and specific modulations in CD23, CD38, CD44 and CD58 expressions. Thus,
      glucocorticoid resistance in RPMI8226 cells is accompanied by significant
      phenotypical alterations that could be implicated in survival enhancement to
      therapy and/or tumor spreading.

PMID- 14687628
TI  - Pancytopenia presenting with monosomy 7 which disappeared after immunosuppressive
      therapy.
AB  - Monosomy 7 syndrome in infant is considered as pre-leukemic condition of poor
      prognosis. However, it seems controversial recently, because some cases of
      monosomy 7 syndrome showed spontaneous remission. We report 2-year-old girl with
      severe pancytopenia, who presented with monosomy 7. Morphologically, there was
      little dysplasia in the trilineage hematopoiesis. Monosomy 7 clone of CD34
      positive cells, bone marrow mononuclear cells (BMMNC), and peripheral nuclear
      cells was 4.0, 40, and 3.8%, respectively. Immunosuppressive therapy was
      effective along with the disappearance of monosomy 7 clone. WT1 mRNA expression
      was not increased in monosomy 7 clone. Pathogenesis of monosomy 7 and its
      relation to aplastic anemia is discussed.

PMID- 14687629
TI  - Biosorption of americium-241 by immobilized Rhizopus arrihizus.
AB  - Rhizopus arrihizus (R. arrihizus), a fungus, which in previous experiments had
      shown encouraging ability to remove 241Am from solutions, was immobilized by
      calcium alginate and other reagents. The various factors affecting 241Am
      biosorption by the immobilized R. arrihizus were investigated. The results showed
      that not only can immobilized R. arrihizus adsorb 241Am as efficiently as free R.
      arrihizus, but that also can be used repeatedly or continuously. The biosorption
      equilibrium was achieved within 2 h, and more than 94% of 241Am was removed from
      241Am solutions of 1.08 MBq/l by immobilized R. arrihizu in the pH range 1-7.
      Temperature did not affect the adsorption on immobilized R. arrihizus in the
      range 15-45 degrees C. After repeated adsorption for 8 times, the immobilized R.
      arrihizus still adsorbed more than 97% of 241Am. At this time, the total
      adsorption of 241Am was more than 88.6 KBq/g, and had not yet reached saturation.
      Ninety-five percent of the adsorbed 241Am was desorbed by saturated EDTA solution
      and 98% by 2 mol/l HNO(3).

PMID- 14687630
TI  - Influence of the chemical form on the plasma clearance of ruthenium in humans.
AB  - The radioisotopes of ruthenium (103Ru and 106Ru) are abundant fission products
      and represent a radiological risk for the population in case of nuclear
      accidents. Few biokinetic studies have been performed on humans up to now and
      consequently the current model recommended by ICRP for ruthenium is derived
      mainly by extrapolation from animal data. The stable isotope 101Ru and proton
      activation analysis have been used to study the biokinetics of Ru in blood plasma
      samples taken during 8 studies in three healthy volunteers. The results obtained
      demonstrated that complexed Ru (in the form of citrate Ru(IV) complexes) is
      cleared from blood plasma very rapidly (characteristic half time of 17+/-2 min),
      while inorganic Ru remains longer in the systemic circulation, and is transferred
      to other organs and/or excreted with a biological half time of 23+/-2h. Good
      reproducibility of the clearance curves indicated no evidence of inter- or intra
      individual variability when the same Ru solution was injected in repeated
      experiments to different subjects.

PMID- 14687631
TI  - In vivo comparison of IVDU and IVFRU in HSV1-TK gene expressing tumor bearing
      rats.
AB  - (E)-5-(2-Iodovinyl)-2'-deoxyuridine (IVDU) and (E)-5-(2-iodovinyl)-2'-fluoro-2'
      deoxyuridine (IVFRU) are potential substrates of Herpes Simplex Virus type 1
      thymidine kinase (HSV-TK). In the present study, cellular uptake of
      radioiodinated substrates was found to be low in wild type MCA cells, but high in
      HSV-TK gene expressing cells. The carrier-free substrates, in particular, showed
      higher cellular uptake than carrier-added compounds. Biodistribution showed that
      the %ID/g of the MCA-TK/MCA tumor ratio of IVDU injected at 1, 4, and 24h were
      1.1, 0.9 and 1.3, and those of IVFRU were 1.7, 1.7 and 1.8 respectively.
      Therefore, both IVDU and IVFRU could possibly be used as radiopharmaceuticals to
      evaluate reporter gene expression. However, IVFRU was more specific and stable
      than IVDU for selective non-invasive imaging of HSV-TK expression.

PMID- 14687632
TI  - A simple effective method for estimating the [18O] enrichment of water mixtures.
AB  - Isotopically enriched water, [18O] H(2)O, recovered from the synthesis of [18F]
      fluorine-labelled PET radiopharmaceuticals, is frequently diluted with natural
      water, [16O] H(2)O. The extent of isotope dilution limits the usefulness of the
      recovered water. A simple method for determining the [18O] enrichment of water
      mixtures could aid PET cyclotron facilities to calculate the [18F] yields to be
      expected when the recovered [18O] H(2)O is reused. A gravimetric method
      (repeatability for high enrichment +/-0.3% [18O], detection limit approximately
      2% [18O] enrichment) is described.

PMID- 14687633
TI  - Radiation dosimetry of O-(3-[18F]fluoropropyl)-L-tyrosine as oncologic PET tracer
      based on the mice distribution data.
AB  - The absorbed and effective radiation doses resulting from the intravenous
      administration of the potential tumor-imaging PET radiopharmaceutical O-(3
      [18F]fluoropropyl)-L-tyrosine (FPT) were estimated using biodistribution data
      from normal mice. The computer program 3P97 and the methodology recommended by
      MIRD were used to estimate the doses. The highest uptake of FPT was found in the
      urinary bladder and pancreas, followed by the liver and kidneys. The urinary
      bladder wall received the highest absorbed dose of 101.0 microGy/MBq for a 70-kg
      standard man. The brain received the lowest dose, 6.5 microGy/MBq. Other organs
      received doses in the range of 6.5-37.5 microGy/MBq. The effective dose was 18.2
      microSv/MBq. The data show that a 370-MBq (10 mCi) injection of FPT would lead to
      an estimated effective dose of 6.7 mSv, which is in the accepted range of routine
      nuclear medicine investigations.

PMID- 14687635
TI  - Performance of CdTe, HPGe and NaI(Tl) detectors for radioactivity measurements.
AB  - The characteristics and performances of the NIST High-Purity Germanium (HPGe),
      Sodium Iodide (NaI(Tl)) and Cadmium Telluride (CdTe) gamma-ray detectors were
      studied. The efficiencies, the minimum detectable activities and the energy
      resolutions of each were measured and compared. The data were analyzed using
      different software packages. The measurements were performed in a low background
      radiation environment using calibrated point sources. The CdTe detector showed a
      higher energy resolution than the NaI(Tl) detector but a lower efficiency than
      both the HPGe and NaI(Tl) detectors. This makes it a suitable detector only for
      relatively high activity measurements restricted to the 35 keV to 200 keV energy
      range.

PMID- 14687636
TI  - Measurement of radon emanation factor from granular samples: effects of additives
      in cement.
AB  - Two methods for radon emanation factor determination were performed and compared
      regarding their measuring accuracy: (a) by hermetically closing the sample in an
      airtight container and measuring the induced radon activity, and (b) by mixing
      charcoal and sealing the sample hermetically and after placing the sample in an
      open vessel with no charcoal addition, measuring each time the 226Ra content
      using gamma-spectrometry. Measurements of radon emanation factor of cement and
      pozzolanic additives, i.e. fly ash and phosphogypsum were also performed.

PMID- 14687637
TI  - Measurement of nitrogen in the body using a commercial PGNAA system--phantom
      experiments.
AB  - An industrial prompt-gamma neutron activation analysis (PGNAA) system, originally
      designed for the real-time elemental analyses of bulk coal on a conveyor belt,
      has been studied to examine the feasibility of using such a system for body
      composition analysis. Experiments were conducted to measure nitrogen in a simple,
      tissue equivalent phantom comprised of 2.7 wt% of nitrogen. The neutron source
      for these experiments was 365 MBq (18.38 microg) of 252Cf located within an
      engineered low Z moderator and it yielded a dose rate in the measurement position
      of 3.91 mSv/h; data were collected using a 2780 cm(3) NaI(Tl) cylindrical
      detector with a digital signal processor and a 512 channel MCA. Source, moderator
      and detector geometries were unaltered from the system's standard configuration,
      where they have been optimized for considerations such as neutron thermalization,
      measurement sensitivity and uniformity, background radiation and external dose
      minimization. Based on net counts in the 10.8 MeV PGNAA nitrogen photopeak and
      its escape peaks the dose dependent nitrogen count rate was 11,600 counts/mSv
      with an uncertainty of 3.0% after 0.32 mSv (4.9 min), 2.0% after 0.74 mSv (11.4
      min) and 1.0% after 3.02 mSv (46.4 min).

PMID- 14687638
TI  - Radioactivity distribution in some Permian sediments from the Irati and
      Corumbatai Formations of the Parana Basin, Southeastern Brazil.
AB  - In the city of Limeira, southeastern Brazil, an important exposure of Permian
      sediments of the Parana basin was revealed by an open pit mine that exploits
      limestone for production of soil correction compounds and raw materials for the
      ceramic industry. The radioactivity of these sediments was investigated in some
      detail and the results provided a general view of the vertical distributions of
      uranium, thorium and potassium concentrations and of the element ratios U/K, U/Th
      and Th/K. In general, the concentrations of the main natural radioactive elements
      are low, with uranium being enriched in some limestone and shale levels. In
      addition the results showed that the 238U series is in radioactive disequilibrium
      in many of the analyzed samples. Although the origin of the observed
      disequilibrium has not been investigated, the results suggest that it is due to
      weathering processes and water interaction with the rock matrix.

PMID- 14687639
TI  - An investigation of the repeatability of calibration factors in gamma-ray
      spectrometry of geological materials.
AB  - A NaI(Tl)-based gamma spectrometer for the analysis of geological materials was
      calibrated using the IAEA reference materials RGU-1, RGTH-1 and RGK-1. To
      simulate typical geological samples, two additional standards were prepared from
      aliquots of the three reference materials. The reproducibility of the instrument
      calibration factors (CFs) was tested by repeated measurements of the pure IAEA
      reference materials and the mixed samples in a reproducible counting geometry.
      The results were analysed using a two-way classification analysis of variance; it
      was found that the variance in the CFs is significantly higher between standards
      than it is between measurements. Allowance should be made for this when
      estimating uncertainties in measurements with the NaI(Tl) spectrometers.

PMID- 14687640
TI  - A simple method for 210Pb determination in geological samples by liquid
      scintillation counting.
AB  - A simple procedure for the determination of 210Pb in geological samples using
      liquid scintillation counting is presented. Following the acid digestion of the
      sample, the method uses sulphate precipitation for the radiochemical separation.
      Finally, lead oxalate is precipitated, and once re-dissolved, it is mixed with
      ULTIMA GOLD AB scintillator cocktail. The measurement is performed using a low
      level LKB Quantulus 1220 spectrometer and the two-window technique. Calibration
      studies were performed to evaluate the interference of 210Bi in the 210Pb
      measurement. The method was tested on a geological reference sample, and gave
      satisfactory results and high reproducibility.

PMID- 14687641
TI  - Determination of thorium concentrations and activity ratios in silicate rocks by
      alpha spectrometry.
AB  - A detailed radiochemical procedure for alpha spectrometry measurements of thorium
      concentrations and of 230Th/232Th activity ratios in silicates is presented. The
      Th behaviour, during each step of the chemical process, was investigated by using
      a 234Th tracer, which is a gamma-ray emitter. The described chemical processing
      provides relatively high thorium yields, which varied between 56% and 88%, in the
      analysis of GB-1 (granite) and BB-1 (basalt) Brazilian geological standards.
      Also, the application of the established radiochemical method allowed a
      determination of both Th concentrations and activity ratios with high
      reproducibility, on the order of 2%. The estimation of the concentration result
      accuracy is also about 2%, which was calculated by using published data obtained
      from neutron activation analysis as reference values.

PMID- 14687642
TI  - Impact of fluoride and other aquatic parameters on radon concentration in natural
      waters.
AB  - Radon (222Rn) accumulation in water in relation to stable elements was studied
      for the purpose of determining factors influencing the transfer of 222Rn to and
      from water. In 72 groundwater samples, 222Rn and about 70 analytical parameters
      were analysed using radiometric and ICP-MS techniques. Using multivariate
      statistics (partial least squares), it was observed that 222Rn has a positive
      correlation with fluoride and uranium. The correlation with fluoride was further
      investigated by a laboratory time-scale experiment to measure the emanation of
      222Rn from water as a function of fluoride, pH and carbonate. The transfer of
      222Rn from water was measured by continuous monitoring in air in a closed loop
      set-up. It was observed that fluoride in water adhere or trap 222Rn preferably in
      acidic water (pH 3). It is suspected that natural physical processes (such as
      diffusion and microbubble phenomenon) are less effective to transport 222Rn in
      the presence of fluoride.

PMID- 14687643
TI  - Radioactivity in local and imported kaolin types used in Egypt.
AB  - Natural radioactive materials are present in all geological rocks in varying
      amounts, they are easily mobilized in the environment, and can reach hazardous
      radiological levels under certain conditions, requiring precautions to be taken.
      The present study deals with 50 geological samples of local (Tushki and Kalabsha
      in upper Egypt) and imported (southeast Asia and Turkey) kaolin types. The
      samples were analyzed by gamma-ray spectroscopy using a HPGe detector. The
      activity concentrations of 232Th and 238U series and 40K and the contents (in
      ppm) are given. The radium equivalent activity varied from 187.8 to 10185.19
      Bq/kg. 137Cs was found in a range of 0.23-8.5 Bq/kg, for the local samples. The
      kaolin in Tushki area was suitable for industrial use.

PMID- 14687644
TI  - Estimation of radiation hazard indices from sedimentary rocks in Upper Egypt.
AB  - The radiological effects from 103 samples of sedimentary rocks from Upper Egypt
      were estimated. The mean values of radium equivalent and representative level
      indices in G. Sarai area are 315.3 Bq/kg and 2.2 while in G. Anz area are 299.4
      Bq/kg and 2.1, respectively. The average absorbed dose rate are 136 and 141.4
      nGy/h for G. Anz and G. Sarai, respectively. These average values give rise to a
      mean effective dose 166.8 and 173.5 microSv/y which are just about 16.7% and
      17.4% of the 1.0 mSv/y recommended by the International Commission on
      Radiological Protection (Radiation Protection: 1990 Recommendations of the
      International Commission on Radiological Protection, Pergamon Press, Oxford,
      1990) as the maximum annual dose to members of the public. The results indicate
      no radiological anomaly. The data presented here will serve as a baseline survey
      for primordial radionuclide concentrations in rocks of the areas.

PMID- 14687647
TI  - Calmodulin, and various ways to regulate its activity.
AB  - Calmodulin (CaM), the ubiquitous calcium sensor protein, is involved in almost
      all intracellular events. In higher vertebrates, a single protein is encoded by
      multiple, co-expressed genes, and the number of discrete CaM transcripts produced
      by a single cell is further increased by intense alternative polyadenylation
      signal usage. It appears most likely that the individual transcripts possess
      unique intracellular fates, so that this apparent redundancy multiplies the
      number of challenges which the cell is able to respond to. The promoter regions
      of the different CaM genes have been analyzed. Several putative transcription
      factor binding sites have been identified; however, the elements responsible for
      their generally strong co-expression, and even those providing different spatial
      and temporal control, remain to be elucidated. Moreover, a powerful
      posttranscriptional control mechanism is responsible for the establishment of
      local intracellular CaM mRNA pools. This is mainly achieved by the selective
      targeting of mRNAs to various cellular domains, although regulation via mRNA
      stability cannot be ruled out. Finally, tailoring of the CaM protein itself
      offers the fastest way whereby the properties of this Ca2+-receptor protein can
      be changed. Indeed, several posttranslational modifications of CaM were described
      earlier, but their functions are not yet understood. Here, we briefly review the
      regulatory levels from the gene transcription to the covalent modifications of
      the synthesized protein.

PMID- 14687648
TI  - Biochemical modulation of Ara-C effects by amidox, an inhibitor of ribonucleotide
      reductase in HL-60 promyelocytic human leukemia cells.
AB  - Amidox, a new polyhydroxy-substituted benzoic acid derivative, is a potent
      inhibitor of the enzyme ribonucleotide reductase (RR), which catalyses the de
      novo synthesis of DNA. RR is considered to be an excellent target for anti cancer
      chemotherapy. We investigated the biochemical and antineoplastic effects of
      amidox as a single agent and in combination with Ara-C in human HL-60
      promyelocytic leukemia cells. Amidox inhibited the growth of HL-60 cells in a
      growth inhibition assay with an IC50 of 25 microM. In a soft agar colony forming
      assay, amidox yielded a 50% inhibition of colony formation at 13 microM. We also
      investigated the effects of amidox treatment on the formation of
      deoxynucleosidetriphosphates. Amidox (50 and 75 microM for 24 hours) could
      significantly decrease intracellular concentrations of dCTP, dATP and dGTP pools,
      whereas dTTP levels increased. We then tested the combination effects of amidox
      with Ara-C; this combination yielded additive cytotoxic effects both in growth
      inhibition and in soft agar colony formation assays. This effect was due to the
      increased formation of Ara-CTP, the active metabolite of Ara-C, after
      preincubation with amidox. Preincubation of HL-60 cells with 75 and 100 microM
      amidox for 24 hours caused an increase in the intracellular Ara-CTP
      concentrations by 576% and 1143%, respectively. Therefore amidox might offer an
      additional option for the treatment of leukemia and thus be further investigated
      in in vivo studies as a single agent and in combination with Ara-C.

PMID- 14687649
TI  - Prediction of viability of porcine neurocysticercosis with proton magnetic
      resonance spectroscopy: correlation with histopathology.
AB  - Neurocysticercosis (NCC) is the most frequent parasitic disease of central
      nervous system. In our earlier study, we had observed creatine [(creatine +
      phosphocreatine); (tCr)] on ex vivo proton MR spectroscopy (1H MRS) in some of
      the cysticercus cyst fluid samples obtained from swine's brain parenchyma. In
      current study, swine brains of freshly slaughtered animals naturally infected
      with NCC were subjected to ex vivo magnetic resonance (MR) imaging on a 1.5Tesla
      MR system. Cysticercus cysts (n = 12) were removed from these brains and were
      labeled depending upon presence or absence of edema around cysts as observed on
      imaging. Cysticercus cyst fluid (100 microl) was subjected to different 1H MRS
      experiments and results were compared with histopathological examinations to look
      for any relationship between tCr and parameters like quantification of
      musculature, and cellular infiltration in wall of the parasite. Histopathology of
      cyst wall was categorized into two groups based on cellular characteristics and
      the amount of musculature. Grade I cysts (n = 5) with no or minimal inflammation
      and large amount of musculature showed tCr on 1H MRS. However, grade II cysts (n
      = 7) with profuse inflammation and less amount of musculature in the cyst wall
      lacked tCr. Higher amount of musculature in grade I cysts was associated with
      higher concentration of tCr in the cyst fluid (r2 = 0.93, P = 0.007). Creatine
      appears to be a marker of innocuous and viable NCC.

PMID- 14687650
TI  - Melatonin treatment protects against sepsis-induced functional and biochemical
      changes in rat ileum and urinary bladder.
AB  - Sepsis is commonly associated with enhanced generation of reactive oxygen
      metabolites, which lead to multiple organ dysfunction. The aim of this study was
      to examine the role of melatonin, a potent antioxidant, in protecting the
      intestinal and bladder tissues against damage in a rat model of sepsis. Sepsis
      was induced by cecal ligation and perforation (CLP) in Wistar Albino rats. Sham
      operated (control) and CLP group received saline or melatonin (10 mg/kg, ip) 30
      minutes prior to and 6 hours after the operation. Sixteen hours after the
      surgery, rats were decapitated and the intestinal and urinary bladder tissues
      were used for contractility studies, or stored for the measurement of
      malondialdehyde (MDA) content -an index of lipid peroxidation-, glutathione (GSH)
      levels -a key antioxidant- and myeloperoxidase (MPO) activity- an index of
      neutrophil infiltration-. Ileal and bladder MDA levels in the CLP group were
      significantly increased (p < 0.001) with concomitant decreases in GSH levels (p <
      0.01 - p < 0.001) when compared to the control group. Similarly, MPO activity was
      significantly increased (p < 0.001) in both ileum and bladder tissues. On the
      other hand, melatonin treatment significantly reversed (p < 0.001) the elevations
      in MDA and MPO levels, while reduced GSH levels were increased back to the
      control levels (p < 0.01 - p < 0.001). In the CLP group, the contractility of the
      ileal and bladder tissues decreased significantly compared with controls.
      Melatonin treatment of the CLP group restored these responses. In this study, CLP
      induced dysfunction of the ileal and bladder tissue of rats was reversed by
      melatonin treatment. Moreover, melatonin, as an antioxidant, abolished the
      elevation in lipid peroxidation products and myeloperoxidase activity, and
      reduction in the endogenous antioxidant glutathione and thus protected the
      tissues against sepsis-induced oxidative damage.

PMID- 14687651
TI  - The endothelin receptor antagonist ameliorates the hypertensive phenotypes of
      transgenic hypertensive mice with renin-angiotensin genes and discloses roles of
      organ specific activation of endothelin system in transgenic mice.
AB  - Endothelin (ET)-1 and ET-2 are potent vasoconstrictor peptides with mitogenic
      activity. In this study, we investigated roles of ET system in renin-angiotensin
      system (RAS)-mediated hypertension, using transgenic hypertensive mice (THM) with
      over-expression of both human renin and angiotensinogen genes. In the first step,
      it was revealed that expression of ET system was locally enhanced, i.e. increases
      in cardiac preproET-1 mRNA and renal preproET-2 mRNA in THM, compared with the
      control (wild type) mice. In the next step, we studied the chronic effects of an
      ET antagonist (SB209670) on THM. Blood pressure (BP) in THM was significantly
      higher than that in the normal mice during the investigation. However, in the
      later phase of the study, from 12 to 20 weeks of treatment, THM receiving SB
      209670 showed significantly lower BP than that in THM receiving saline. SB 209670
      treatment for 20 weeks significantly attenuated phenotypes of cardiac
      hypertrophy, vascular wall thickening and hypertensive nephropathy observed in
      THM, suggesting that the ETA/B receptor antagonist is also effective even in the
      extraordinarily activated RAS condition. These findings suggest that organ
      specifically activated ET system in THM develops the phenotypes, hypertension,
      cardiac hypertrophy, and hypertensive nephropathy.

PMID- 14687652
TI  - Evidence for biological rhythm in spermatogenesis in the pubertal hamster
      (Mesocricetus auratus): a flow cytometric study.
AB  - The number of cells in the S-phase fraction of the cell cycle reflects
      proliferative activity. Using flow cytometry histograms and the Phoenix M+ cell
      cycle program, the percent of cells in the S-phase fraction was measured in
      single cell suspensions prepared from testes of hamsters of different ages. A
      cyclical pattern with a period of 9 days, superimposed on another rhythm with a
      38 day period was observed (p < 0.01) during hamster maturation and it
      disappeared after the second spermatogenic wave, where the S phase values reached
      a plateau. It was concluded that maturing animals passed through a stage in which
      testicular biological rhythm was involved. Therefore it was concluded that it
      takes approximately two spermatogenic waves before the proliferation rate in the
      testis reached a steady state.

PMID- 14687653
TI  - Early preconditioning prevents the loss of endothelial nitric oxide synthase and
      enhances its activity in the ischemic/reperfused rat heart.
AB  - Cardiac ischemia may be responsible for either the loss of endothelial nitric
      oxide synthase (eNOS) or changes in its activity, both conditions leading to
      coronary dysfunction. We investigated whether early ischemic preconditioning was
      able to preserve eNOS protein expression and function in the ischemic/reperfused
      myocardium. Langendorff-perfused rat hearts were subjected to 20 min global
      ischemia, followed by 30 min reperfusion (I/R). A second group of hearts was
      treated as I/R, but preconditioned with three cycles of 5 min-ischemia/5 min
      reperfusion (IP). Cardiac contractility markedly decreased in I/R, consistently
      with the rise of creatine kinase (CK) activity in the coronary effluent, whilst
      ischemic preconditioning significantly improved all functional parameters and
      reduced the release of CK. Western blot analysis revealed that the amount of eNOS
      protein decreased by 54.2% in I/R with respect to control (p < 0.01). On the
      other hand, NOS activity was not significantly reduced in I/R, as well as cGMP
      tissue levels, suggesting that a parallel compensatory stimulation of this
      enzymatic activity occurred during ischemia/reperfusion. Ischemic preconditioning
      completely prevented the loss of eNOS. Moreover, both NOS activity and cGMP
      tissue level were significantly higher (p < 0.05) in IP (12.7 +/- 0.93
      pmol/min/mg prot and 58.1 +/- 12.2 fmol/mg prot, respectively) than I/R (7.34 +/-
      2.01 pmol/min/mg prot and 21.4 +/- 4.13 fmol/mg prot, respectively). This suggest
      that early ischemic preconditioning may be useful to accelerate the complete
      recovery of endothelial function by preserving the level of cardiac eNOS and
      stimulating the basal production of nitric oxide.

PMID- 14687654
TI  - Low level lead (Pb) exposure during gestation and lactation: assessment of
      effects on pubertal development in Fisher 344 and Sprague-Dawley female rats.
AB  - Studies using both Fisher 344 and Sprague-Dawley (SD) rat lines have shown that
      gestational and/or lactational maternal lead (Pb) exposure causes delayed
      reproductive maturation in their respective female offspring. Because these
      studies utilized different experimental regimens for dosing and for monitoring Pb
      levels, it has not been possible to determine which rat line provides the best
      model for low level Pb toxicity studies. This study was designed to address this
      issue. Adult Fisher and SD female rats were dosed with either a solution of PbAc
      containing 12 mg of Pb/ml or sodium acetate (NaAc) for controls. Dosing began 30
      days prior to breeding and continued until their pups were weaned at 21 days of
      age. At the time of breeding and through weaning the blood lead (BPb) levels in
      the Fisher dams averaged 37.3 microg/dl and the SD dams averaged 29.9 microg/dl.
      Pb delayed the timing of puberty (p < 0.01) in Fisher offspring, and suppressed
      serum levels of luteinizing hormone (LH, p < 0.001) and estradiol (E2, p < 0.01).
      These effects did not occur in the SD offspring. Doubling the dose given to the
      SD rats increased their BPb levels to 62.6 microg/dl, yet there were still no
      effects noted. These results indicate that Fisher offspring are more sensitive to
      maternal Pb exposure with regard to puberty related insults than are SD rats,
      suggesting that the Fisher line may be a more reliable rodent model to study the
      effects of low level Pb toxicity.

PMID- 14687655
TI  - Taraxacum officinale induces cytotoxicity through TNF-alpha and IL-1alpha
      secretion in Hep G2 cells.
AB  - Taraxacum officinale (TO) has been frequently used as a remedy for women's
      disease (e.g. breast and uterus cancer) and disorders of the liver and
      gallbladder. Several earlier studies have indicated that TO exhibits anti-tumor
      properties, but its mechanism remains to be elucidated. In this study, we
      investigated the effect of TO on the cytotoxicity and production of cytokines in
      human hepatoma cell line, Hep G2. Our results show that TO decreased the cell
      viability by 26%, and significantly increased the tumor necrosis factor (TNF)
      alpha and interleukin (IL)-1alpha production compared with media control (about
      1.6-fold for TNF-alpha, and 2.4-fold for IL-1alpha, P < 0.05). Also, TO strongly
      induced apoptosis of Hep G2 cells as determined by flow cytometry. Increased
      amounts of TNF-alpha and IL-1alpha contributed to TO-induced apoptosis. Anti-TNF
      alpha and IL-1alpha antibodies almost abolished it. These results suggest that TO
      induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

PMID- 14687656
TI  - Characteristics of piraltin, a polyphenol concentrate, produced by freeze-drying
      of red wine.
AB  - Moderate consumption of red wine is associated with a decreased risk for coronary
      heart disease. Apart from alcohol, an additive role for wine polyphenols has been
      suggested. However, the real contribution of these compounds can only be studied
      when available without the alcohol component. The objective of the study was to
      prepare a wine polyphenol concentrate not containing alcohol and to compare the
      quantitative and qualitative properties of this concentrate with those of the
      original wine from which the concentrate is made. This polyphenol concentrate,
      called piraltin, was made out of red wine by a freeze-drying technique. Both
      piraltin and the original red wine were analyzed quantitatively for the main
      polyphenols present: gallic acid, catechin, epicatechin and quercetin. The
      qualitative comparison comprised the inhibitory effect of the two products on LDL
      oxidation in vitro. In the process of freeze-drying recovery of the four
      determined flavonoids of red wine is fairly constant (average 68 +/- 7%). In a
      copper induced LDL oxidation assay both red wine and piraltin prolonged lag-times
      over 300% compared to controls without a significant difference between the two
      products. The freeze-dried polyphenol concentrate piraltin contains about 70% of
      the total polyphenol content of the original wine. This preparation technique
      does not cause a loss of antioxidative properties of the phenols. Piraltin
      creates the possibility to study the effects of wine polyphenols separately
      without the influence of alcohol both in vitro and in vivo.

PMID- 14687657
TI  - Involvement of nitric oxide in the gastroprotective effects of an aqueous extract
      of Pfaffia glomerata (Spreng) Pedersen, Amaranthaceae, in rats.
AB  - The plants belonging to Pfaffia genus are used in folk medicine to treat gastric
      disturbances. This study examined the effects of an aqueous extract of Pfaffia
      glomerata (Spreng) Pedersen (AEP) on the gastrointestinal tract. Wistar rats were
      pretreated orally (p.o.) with the AEP (125, 250, 500 and 1000 mg.kg(-1)) before
      induction of ulcers by hypothermic restraint stress (HRS, 3 h restraint stress at
      4 degrees C), ethanol (ET, 70%; 0.5 ml/animal; p.o.) or indomethacin (IND, 20
      mg.kg(-1); s.c.). Control animals received water (C) or ranitidine (60 mg.kg(-1))
      p.o. The AEP protected rats against HRS and ET-induced ulcers, but was not able
      to protect the gastric mucosa against IND-induced ulcers. When injected into the
      duodenal lumen, the AEP reduced total acidity and both basal and histamine
      stimulated acid secretion in pylorus-ligated rats. In addition, gastric secretion
      from AEP-treated animals exhibited increased concentrations of nitrite and
      nitrate. Treatment of animals with L-NAME (120 mg.kg(-1), p.o.) prevented both
      the reduction of total acidity and the increase in NOx levels promoted by AEP
      treatment. In conclusion, AEP effectively protected the gastric mucosa and
      inhibited gastric acid secretion in rats, probably by involving the histaminergic
      pathway and an enhanced production of nitric oxide in the stomach.

PMID- 14687658
TI  - Adenosine 5'-(gamma-thio) triphosphate (ATPgammaS) stimulates both P2Y receptors
      linked to inositol phosphates production and cAMP accumulation in bovine
      adrenocortical fasciculata cells.
AB  - The study was aimed to investigate the existence of at least two kinds of P2Y
      receptors linked to steroidogenesis in bovine adrenocortical fasciculata cells
      (BAFCs). Extracellular nucleotides facilitated steroidogenesis in BAFCs. The
      potency order was UTP > adenosine 5'-(gamma-thio) triphosphate (ATPgammaS) > ATP
      > 2-methylthio ATP (2MeSATP) > adenosine 5'-(beta-thio) diphosphate (ADPbetaS) >
      alpha,beta-methylene ATP (alpha,beta-me-ATP), beta,gamma-methylene ATP
      (beta,gamma -me-ATP). ATPgammaS (10-100 microM) remarkably stimulated both total
      inositol phosphates (IPs) production and cyclic AMP (cAMP) accumulation.
      Competitive displacement experiments by using [35S]ATPgammaS as a radioactive
      ligand in BAFCs showed that the potency under these unlabelled ligands was
      ATPgammaS > ATP > ADPbetaS > 2MeSATP > UTP > alpha,beta-me-ATP, beta,gamma-me
      ATP. These suggest that two different binding sites of [35S]ATPgammaS, namely P2Y
      receptors, exist in BAFCs, and that these receptors are linked to steroidogenesis
      via distinct second messenger systems in the cells.

PMID- 14687659
TI  - Signal transduction of bone morphogenetic protein receptors.
AB  - Bone morphogenetic proteins (BMPs) play a crucial role during all stages of
      embryonic development. Although only two major signaling pathways have been
      characterized (the p38 and Smad pathways), the BMP signaling is complex and
      includes several negative feedback mechanisms. This article reviews the current
      state of BMP receptor signaling and provides a summary of the crosstalk of the
      BMP receptor pathway with other major signaling pathways.

PMID- 14687660
TI  - Selective down-regulation of angiotensin II receptor type 1A signaling by protein
      tyrosine phosphatase SHP-2 in vascular smooth muscle cells.
AB  - The heptahelical AT(1) G-protein-coupled receptor lacks inherent tyrosine kinase
      activity. Angiotensin II binding to AT(1) nevertheless activates several tyrosine
      kinases and stimulates both tyrosine phosphorylation and phosphatase activity of
      the SHP-2 tyrosine phosphatase in vascular smooth muscle cells. Since a balance
      between tyrosine kinase and tyrosine phosphatase activities is essential in
      angiotensin II signaling, we investigated the role of SHP-2 in modulating
      tyrosine kinase signaling pathways by stably transfecting vascular smooth muscle
      cells with expression vectors encoding wild-type SHP-2 protein or a catalytically
      inactive SHP-2 mutant. Our data indicate that SHP-2 is an efficient negative
      regulator of angiotensin II signaling. SHP-2 inhibited c-Src catalytic activity
      by dephosphorylating a positive regulatory tyrosine 418 within the Src kinase
      domain. Importantly, SHP-2 expression also abrogated angiotensin II-induced
      activation of ERK, whereas expression of catalytically inactive SHP-2 caused
      sustained ERK activation. Thus, SHP-2 likely regulates angiotensin II-induced MAP
      kinase signaling by inactivating c-Src. These SHP-2 effects were specific for a
      subset of angiotensin II signaling pathways, since SHP-2 overexpression failed to
      influence Jak2 tyrosine phosphorylation or Fyn catalytic activity. These data
      show SHP-2 represents a critical negative regulator of angiotensin II signaling,
      and further demonstrate a new function for this phosphatase in vascular smooth
      muscle cells.

PMID- 14687661
TI  - Heat shock protein 90 suppresses tumor necrosis factor alpha induced apoptosis by
      preventing the cleavage of Bid in NIH3T3 fibroblasts.
AB  - Two highly conserved mechanisms for maintaining cellular homeostasis are
      apoptosis and the cellular stress response. Hsp90 is one of the most abundant,
      highly conserved, and inducible Hsps in eukaryotes. Recently, Hsp90 has been
      shown to play important antiapoptotic roles through binding with Apaf-1, RIP and
      kinase domain of IKKalpha/beta. Our present studies demonstrate that Hsp90 can
      suppress tumor necrosis factor alpha (TNFalpha)-induced apoptosis in stable Hsp90
      overexpressing NIH3T3 cells by preventing the cleavage of Bid. The prevention of
      the cleavage of Bid can be partially explained by the direct interaction between
      Hsp90 and Bid. Furthermore, disrupting the function of Hsp90 by the addition of
      its specific inhibitor, geldanamycin, blocked Hsp90's protection of Bid cleavage.
      These results show that Hsp90 can function at different levels within apoptotic
      signal transduction pathways.

PMID- 14687662
TI  - Integration of multiple downstream signals determines the net effect of insulin
      on MAP kinase vs. PI 3'-kinase activation: potential role of insulin-stimulated
      H(2)O(2).
AB  - Cellular insulin stimulation generates a burst of H(2)O(2) that modulates protein
      tyrosine phosphorylation in the insulin action pathway, in part by the inhibition
      of redox-sensitive protein-tyrosine phosphatases [J. Biol. Chem. 276 (2001)
      21938]. Blocking the insulin-induced rise in H(2)O(2) with the NADPH oxidase
      inhibitor diphenyleneiodonium (DPI) strongly attenuated the activation of
      phosphatidylinositol 3' (PI 3')-kinase, Akt and GLUT4 translocation by insulin in
      3T3-L1 adipocytes; however, under identical conditions, we observed a paradoxical
      increase in the activation of p42/p44 mitogen-activated protein (MAP) kinase. DPI
      inhibited the insulin-stimulated tyrosine phosphorylation of the insulin receptor
      and IRS-1/2, and also reduced the association of Grb2 with IRS-1, suggesting that
      the effect of DPI on MAP kinase activation occurred downstream of the IR and IRS
      proteins. DPI increased the insulin-stimulated phosphorylation of p42/p44 MAP
      kinase with no change in basal, and increased insulin-stimulated MAP kinase
      kinase (MEK) activity by a similar degree. DPI enhanced basal Grb2-Sos binding
      and reduced the effect of insulin to potentiate the dissociation of the Grb2-Sos
      complex, suggesting that the effect of DPI was mediated upstream of Raf-1. Cell
      treatment with dibutyryl cAMP significantly reduced the enhancement of MAP kinase
      activation in the presence of DPI. However, forskolin, acting in a PKA
      independent manner, increased the insulin stimulation of MAP kinase and MEK, but
      fully abrogated the effect of DPI to enhance these insulin responses. PLCgamma
      inhibition with U73122 blocked the insulin stimulation of MAP kinase and MEK as
      well as the enhancing effect of DPI on these responses. PKC activation strongly
      stimulated MAP kinase and MEK activation, even in the presence of U73122,
      consistent with PKC acting downstream of PLCgamma. These data show that the
      insulin-stimulated oxidant signal differentially affects the two major downstream
      components of the insulin signaling pathway, PI 3'-kinase and MAP kinase, and
      cross-talk between insulin action, PLCgamma and, to a lesser extent, PKA
      modulates the net cellular effects of insulin-stimulated cellular H(2)O(2).

PMID- 14687663
TI  - Protein tyrosine kinase-dependent modulation of voltage-dependent potassium
      channels by genistein in rat cardiac ventricular myocytes.
AB  - Effects of the isoflavone protein tyrosine kinase (PTK) inhibitor genistein on
      voltage-dependent K(+) currents, i.e., transient outward K(+) current (I(to)),
      sustained K(+) current (I(ss)), and inward rectifier K(+) current (I(K1)) were
      studied in rat cardiac ventricular myocytes. It was found that I(to) was
      reversibly inhibited by genistein in a concentration-dependent manner
      (IC(50)=28.1 microM), while I(ss) was suppressed by genistein with IC(50) of 18.5
      microM. In addition, I(K1) (at -50 mV) was significantly decreased by 36.3+/-4.4%
      with 25 microM genistein. The inhibition of I(to), I(ss), and I(K1) by genistein
      was significantly reversed by the application of the protein tyrosine phosphatase
      inhibitor sodium orthovanadate (1 mM). However, I(to), I(ss), and I(K1) were not
      affected by the non-isoflavone PTK inhibitor tyrphostin A23 (100 microM) and PP2
      (1 microM). These results indicate that activation of I(to), I(ss), and I(K1)
      channels is modulated by genistein-sensitive PTKs in rat ventricular myocytes.

PMID- 14687664
TI  - Redox regulates COX-2 upregulation and cell death in the neuronal response to
      cadmium.
AB  - We reported previously that cadmium, an oxidative stressor, induced
      cyclooxygenase-2 (COX-2) upregulation in mouse neuronal cells that culminated in
      cell death. Herein, we show that cadmium induces reactive oxygen species (ROS)
      that activate c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein
      kinase (MAPK) and their substrates, activating transcription factor 2 (ATF-2),
      CRE-binding protein (CREB) and c-Jun. This response is accompanied by induction
      of heme-oxygenase-1 (HO-1), poly(ADP-ribose) polymerase cleavage and a caspase
      independent cell death. Inhibition of p38 MAPK, but not JNK, suppressed COX-2
      protein expression and the cytotoxic response induced by cadmium. Selective
      inhibitors of phosphatidylinositol-3-kinase (PI3-K), LY294002, and flavoproteins,
      dipheneylene iodonium chloride (DPI), attenuated cadmium-induced ROS and stress
      kinase activation, suggesting that ROS can signal the COX-2 upregulation and
      neuronal cell death mediated by p38 MAPK. Collectively, these findings implicate
      PI3-K, a flavoprotein, p38 MAPK and COX-2 in a neuronal redox-regulated pathway
      that mediates cadmium-induced oxidative stress.

PMID- 14687665
TI  - Differential signalling of NH2-terminal flag-labelled thrombopoietin receptor
      activated by TPO or anti-FLAG antibodies.
AB  - In this report, we compared activation of NH2-terminal FLAG-labelled
      thrombopoietin receptor (Mpl) by anti-FLAG antibodies and by thrombopoietin
      (TPO). We found that anti-FLAG monoclonal antibodies M1 dimerize FLAG-labelled
      receptor and trigger proliferation of BaF3/FLAG-Mpl cells. In UT7/FLAG-Mpl cells,
      activation of the FLAG-Mpl receptor by low TPO concentrations triggered
      proliferation, while high concentrations triggered differentiation. Activation of
      FLAG-Mpl receptors in these cells by all tested concentrations of M1 antibodies
      induced proliferation but not differentiation. Low TPO concentrations induced
      similar to M1 antibodies level of Jak2, Stat3, Stat5 and Akt phosphorylation. In
      contrast, only TPO and not M1 antibodies activated Erks phosphorylation. Since
      the anti-FLAG antibodies do not react with the TPO binding site of the receptor,
      we hypothesize that they can trigger a distinct signal by dimerizing Mpl in a
      manner different from that induced by TPO.

PMID- 14687666
TI  - Differentiation of human monocytes in vitro with granulocyte-macrophage colony
      stimulating factor and macrophage colony-stimulating factor produces distinct
      changes in cGMP phosphodiesterase expression.
AB  - The cytokines macrophage colony-stimulating factor (M-CSF) and granulocyte
      macrophage colony-stimulating factor (GM-CSF) promote differentiation of
      monocytes into macrophages with distinct phenotypes and unique functional
      abilities. In this report, we characterize how monocytes and macrophages
      differentiated from monocytes with M-CSF and GM-CSF regulate their cGMP levels by
      controlling which phosphodiesterases (PDEs) and guanylyl cyclases (GCs) are
      expressed. We find that PDE1B and PDE2A are expressed at low levels in monocytes,
      but are the major cGMP PDEs expressed in macrophages. M-CSF differentiation
      triggers increased expression of PDE1B and PDE2A, while GM-CSF causes a large
      increase only in PDE1B. Based on PDE expression, we identified THP-1 and U937
      cell lines as possible models for studying the roles of PDE1B and PDE2A in
      macrophage function. We additionally characterized changes in expression of GCs
      upon differentiation. We found that GM-CSF differentiation triggers a small
      decrease in soluble guanylyl cyclase (sGC) and a large increase in GC-A, while M
      CSF significantly decreases sGC.

PMID- 14687667
TI  - CD40-mediated activation of vascular smooth muscle cell chemokine production
      through a Src-initiated, MAPK-dependent pathway.
AB  - The interaction between CD40 ligand (CD154) expressed on activated T cells and
      its receptor, CD40, has been shown to play a role in the onset and maintenance of
      autoimmune inflammation. Recent studies suggest that CD154+T cells also
      contribute to the regulation of atherogenesis due to their capacity to activate
      CD40+cells of the vasculature, including vascular smooth muscle cells (VSMC). The
      present study evaluated the signalling events initiated through CD40 ligation
      which culminate in VSMC chemokine production. CD40 ligation resulted in the
      phosphorylation/activation of mitogen-activated protein kinases (MAPKs),
      extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p38, but not c-jun N
      terminal kinase. Inhibition of both ERK1/2 and p38 activity abrogated CD40
      stimulation of IL-8 and MCP-1 production. CD40-mediated induction of chemokines
      also showed dependence on the Src family kinase activity. The Src kinase
      inhibitor, PP2, was found to inhibit CD40-induced phosphorylation of ERK1/2 as
      well as activation of IkappaB kinase. An evaluation of Src kinases that may be
      important in CD40 signalling identified Lyn as a potential candidate. These data
      indicate that CD40 signalling in VSMC activates a Src family kinase-initiated
      pathway that results in the induction of MAPK activities required for successful
      induction of chemokine synthesis.

PMID- 14687669
TI  - A method for peripheral chromatolysis in neurons of trigeminal and dorsal root
      ganglia, produced in rats by lithium.
AB  - In classical chromatolysis, Nissl bodies are initially lost centrally with
      subsequent progression to the periphery of the neuron. Peripheral chromatolysis
      has the opposite pattern; it is less common and more difficult to produce. We
      describe a new method for producing peripheral chromatolysis in neurons of
      trigeminal ganglia and dorsal root ganglia that requires only injection of large
      doses of lithium chloride (LiCl) for two, three or four consecutive daily doses.
      This method may be useful for elucidating the intraneuronal mechanisms that
      control the location and structure of the Nissl bodies.

PMID- 14687668
TI  - Mice with transgenic overexpression of lipid phosphate phosphatase-1 display
      multiple organotypic deficits without alteration in circulating lysophosphatidate
      level.
AB  - Lipid phosphate phosphatase 1 (LPP-1) is presumed to regulate the balance between
      lipid phosphates and their dephosphorylated counterparts. The currently
      prevailing hypothesis based on in vitro studies proposes that LPP-1 should
      regulate phospholipid lipid growth factors and second messengers, including
      lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P), diacylglycerol (DAG),
      and phosphatidic acid (PA). To evaluate the role of LPP-1 in vivo, three
      transgenic lines were established. RT-PCR, Western blotting, and enzymatic
      activity measurement confirmed a copy number-dependent ubiquitous overexpression
      of LPP-1. PMA-stimulated PA production in immortalized LPP-1 fibroblasts led to
      an elevation in the accumulation of DAG without major changes in the phospholipid
      classes isolated from the liver. The LPP-1 phenotype showed reduced body size,
      birth weight, and abnormalities in fur growth, whereas histological abnormalities
      included significantly decreased number of hair follicles, disrupted hair
      structure, and a severely impaired spermatogenesis. Implantation of LPP-1 or wild
      type embryos into pseudopregnant LPP-1 mothers yielded a reduced litter size. The
      plasma level of alanine-leucine aminotransferase was significantly elevated.
      Unexpectedly, plasma concentrations of the five major acyl-species of LPA were
      indistinguishable between wild-type and LPP-1 animals. In contrast with previous
      studies using plasmid-mediated overexpression in vitro, transgenic overexpression
      of LPP-1 did not affect ERK1/2 activation elicited by LPA, S1P, thrombin,
      epidermal growth factor (EGF), and platelet-derived growth factor (PDGF), which
      was presumed to be a major signaling event regulated by LPP-1. Thus, transgenic
      overexpression of LPP-1 in mice elicited a number of unexpected phenotypic
      alterations without affecting several aspects of LPA signaling, which point to
      previously unappreciated mechanisms and roles of lipid phosphates in select
      organs.

PMID- 14687670
TI  - A novel version of the 8-arm radial maze: effects of cerebral ischemia on
      learning and memory.
AB  - A novel version of the 8-arm radial maze task was developed to quantify spatial
      learning and memory in rats subjected to transient cerebral ischemia (TCI) using
      the 4-VO model. This maze uses the rat's natural behavior of avoiding open,
      illuminated areas, and preference for a darkened, enclosed shelter. Ischemic rats
      were required to escape from the central area into the darkened goal box.
      Ischemia was induced before or after training to examine its influence on
      acquisition and retention of cognition, respectively. During the acquisition
      test, latency of ischemic rats to find the goal box, and working memory
      performance were significantly impaired (P < 0.005-0.001). The performance for
      retention of cognition was also disrupted by ischemia (P < 0.05-0.01). There was
      no correlation between the degree of CA1 pyramidal cell loss and behavioral
      deficits. The present data reveal that the aversive version of the 8-arm radial
      maze is sensitive to the cognitive effects of ischemia. Since it excludes the
      need for food deprivation or immersion of the animal in water, the method should
      provide a sensitive and more practical behavioral test with which to evaluate the
      effects of ischemic brain damage on cognition.

PMID- 14687671
TI  - A method for intraoperative microneurographic recording of unitary activity in
      the trigeminal ganglion of patients with trigeminal neuralgia.
AB  - The etiology of trigeminal neuralgia appears to be vascular compression of the
      nerve at the root entry zone. However, the physiologic mechanism of trigeminal
      neuralgia remains uncertain. To gain insight into the pathophysiology of the
      disorder, we developed a method for intraoperative microneurographic recordings
      from the trigeminal ganglion of patients with trigeminal neuralgia. The
      recordings are performed immediately prior to standard percutaneous trigeminal
      gangliolysis for pain relief. Spontaneous or evoked single- and multi-unit action
      potential activity can be recorded and the location of receptive fields
      determined. The method should facilitate the testing of hypotheses concerning the
      origin of this unique pain disorder.

PMID- 14687672
TI  - Chronically implanted epineural electrodes for repeated assessment of nerve
      conduction velocity and compound action potential amplitude in rodents.
AB  - Implanted epineural electrodes were used for the longitudinal assessment of
      peripheral nerve conduction velocity (NCV) and compound action potential (CAP)
      amplitude in rats. Custom-fabricated stimulating and recording electrodes were
      sutured over the tibial and sciatic nerves, respectively, and were used for
      weekly recordings of CAP latency and amplitude. Intra-day variability of nerve
      conduction velocity measurements had coefficients of variation of less than 2%
      for same day recordings from individual subjects. A clear trend in recovery of
      the NCV values following implant was observed over the 7-week trial period. These
      results demonstrate that implanted epineural electrodes provide a reliable method
      for chronic, in vivo monitoring of nerve conduction parameters in rodents.

PMID- 14687673
TI  - From artificial cerebro-spinal fluid (aCSF) to artificial extracellular fluid
      (aECF): microdialysis perfusate composition effects on in vivo brain ECF glucose
      measurements.
AB  - Microdialysis (mD) is the predominant technique for measurements of brain
      chemistry, especially when such measurements are made in awake animals.
      Relatively little attention has been paid, however, to the potential effect on
      such measurements of variation in the perfusate solution used. Here, we report
      that small variations in the ionic composition of microdialysis perfusate
      produced four-fold differences (0.53-2.18 mM) in the results obtained when
      measuring brain extracellular fluid (ECF) glucose. These changes may be linked to
      concomitant alterations of local neural activity caused by the perfusate
      composition. In addition to perfusate composition, probe type also proved to have
      a significant impact on microdialysis measurements. Further, we report the first
      direct microdialysis measurements of brain ECF ionic composition, showing
      significant differences from that of the cerebro-spinal fluid (CSF). Modifying
      the ionic composition of microdialysis perfusate based on these measurements
      resulted in a measured hippocampal ECF glucose level of 1.26 +/- .04 mM.
      Increased understanding of the impact of differences in the perfusate solutions
      used by different laboratories may provide a basis for reconciliation of
      apparently disparate microdialysis results within the literature.

PMID- 14687674
TI  - Reliability of the NeuroTrend sensor system under hyperbaric conditions.
AB  - OBJECTIVE: The goal of this study was to investigate the reliability of the multi
      parameter sensor NeuroTrend in a hyperbaric environment for up to 3bar absolute
      pressure. Measurement of brain tissue oxygenation (ptiO2) under hyperbaric
      conditions is supposed to elucidate whether hyperbaric oxygenation therapy has
      the potential to improve ptiO2 to a clinically significant degree in pathological
      altered brain tissue after traumatic brain injury. METHODS: The NeuroTrend sensor
      hose, filled with equilibrated plasma samples, was stored in a decompression
      chamber. The plasma samples were equilibrated with three different gas mixtures.
      After determination of the initial values for temperature, oxygen partial
      pressure (pO2), carbon dioxide partial pressure (pCO2) and hydrogen ion
      concentration (pH) in the plasma, the ambient pressure was stepwise increased
      from 0.1 to 3 bar. The same set-up was performed without increasing the ambient
      pressure. RESULTS: No significant difference in the mean values for all 23
      measurement points and for all parameters (pO2, pCO2, pH) of all 10 NeuroTrend
      sensors was found, under both normobaric and hyperbaric conditions. CONCLUSION:
      The study demonstrated that an absolute ambient pressure up to 3 bar did not
      influence the measuring properties and the reliability of the NeuroTrend sensor.

PMID- 14687675
TI  - A microarray platform comparison for neuroscience applications.
AB  - To address the need for high sensitivity in gene expression profiling of small
      neural tissue samples ( approximately 100 ng total RNA), we compared a novel RT
      PCR-IVT protocol using fluor-reverse pairs on inkjet oligonucleotide microarrays
      and an RT-IVT protocol using 33P labeling on nylon cDNA arrays. The comparison
      protocol was designed to evaluate these systems for sensitivity, specificity,
      reproducibility, and linearity. We developed parameters, thresholds, and testing
      conditions that could be used to differentiate various systems that spanned
      detection chemistry and instrumentation; probe number and selection criteria; and
      sample processing protocols. We concluded that the inkjet system had better
      performance in sensitivity, specificity, and reproducibility than the nylon
      system, and similar performance in linearity. Between these two platforms, the
      data indicates that the inkjet system would perform better for the
      transcriptional profiling of 100 ng total RNA samples for neuroscience studies.

PMID- 14687676
TI  - A vertical flow chamber for Xenopus oocyte electrophysiology and automated drug
      screening.
AB  - Xenopus laevis oocytes are used extensively in the study of ion channel coupled
      receptors. Efficient use of oocytes for ion channel characterization requires a
      system that is inherently stable, reproducible, minimizes drug volumes, and
      maximizes oocyte longevity. We have constructed a vertical flow oocyte recording
      chamber to address the aforesaid issues, where the oocyte is placed in a funnel
      shaped chamber and perfused from the bottom of the funnel. The vertical rather
      than horizontal flow of perfusate results in an unusually stable environment for
      oocyte recording. Two-electrode voltage clamp recordings from a single oocyte are
      acquired easily and routinely over several hours while maintaining stable
      baseline currents and reproducible response profiles. Chamber characteristics
      were tested using a serotonin ligand-gated ion channel receptor (5-HT3R). Data
      obtained from this system corresponds well with published data. To further test
      the stability and reliability of this perfusion chamber, we constructed an
      automated oocyte perfusion system utilizing a commonly available HPLC
      autosampler. We were able to obtain dose-response curves for various 5-HT3AR
      ligands using the automated perfusion system with minimal user intervention. Such
      a system can easily satisfy need for automated oocyte electrophysiology in
      academic settings, especially small to medium sized laboratories.

PMID- 14687677
TI  - Electroporation loading and photoactivation of caged InsP3: tools to investigate
      the relation between cellular ATP release in response to intracellular InsP3
      elevation.
AB  - Photolytic liberation of InsP(3) in single cells triggers cell-to-cell
      propagating calcium changes that are communicated by a gap junctional and a
      paracrine purinergic pathway involving InsP(3)-triggered ATP release. We
      investigated the relation between the InsP(3) stimulus and the resulting ATP
      release in ECV304 cells using UV photolysis of caged compounds and bioluminescent
      ATP measurements. Careful consideration of all steps, starting from caged InsP(3)
      loading into the cells by electroporation, up to photoliberation upon UV
      exposure, allowed to derive a dose-response relation that revealed a first part
      with a flattening ATP release response in the below 10microM InsP(3)
      concentration range and a second phase of steeply increasing ATP release in
      response to above 10microM InsP(3) stimulation. ATP release triggered by below
      10microM InsP(3) concentrations attained a level in the order of 30% above
      baseline ATP release, while the steeply increasing response to high InsP(3)
      concentrations attained values in the order of 150% above baseline. Our data
      indicate the involvement of low affinity InsP(3) receptor sites in the pathway
      leading to triggered ATP release, with activation of these receptors causing the
      release of 1-2% of the total cellular ATP pool.

PMID- 14687678
TI  - Sensitivity of temporal excitation properties to the neuronal element activated
      by extracellular stimulation.
AB  - Measurements of the chronaxies and refractory periods with extracellular stimuli
      have been used to conclude that large diameter axons are responsible for the
      effects of deep brain stimulation (DBS). We hypothesized that because action
      potential initiation by extracellular stimulation occurs in the axons of central
      nervous system (CNS) neurons, the chronaxies and refractory periods determined
      using extracellular stimulation would be similar for cells and axons. Computer
      simulation was used to determine the sensitivity of chronaxie and refractory
      period to the neural element stimulated. The results demonstrate that chronaxies
      and refractory periods were dependent on the polarity of the extracellular
      stimulus and the electrode-to-neuron distance, and indicate that there is little
      systematic difference in either chronaxies or refractory periods between local
      cells or axons of passage with extracellular stimulation. This finding points out
      the difficulty in drawing conclusions regarding which neuronal elements are
      activated based on extracellular measurements of temporal excitation properties.

PMID- 14687679
TI  - The use of real-time PCR analysis in a gene expression study of Alzheimer's
      disease post-mortem brains.
AB  - The measurement of gene expressions in brains with neurodegenerative diseases is
      a major area of brain research. The objective of our research was to determine
      whether quantitative real-time PCR could measure messenger RNA (mRNA) expression
      in brains with post-mortem intervals beyond 12h. In the present paper, we
      examined the quality of RNA from brain specimens of both Alzheimer's disease (AD)
      patients (n = 13) and non-demented normal control subjects (n = 6). To determine
      a unregulated endogenous reference gene in AD, we measured mRNA expressions of
      the commonly used reference genes beta-actin, 18S rRNA, and GAPDH. In addition,
      we determined whether post-mortem interval, brain weight, or age at death
      influences mRNA expression. Our real-time PCR analysis results indicate that mRNA
      expression can be detected in all brain specimens for beta-actin, 18S rRNA,
      GAPDH, and also synaptophysin, a known marker for AD. Further, using real-time
      PCR analysis, we found that beta-actin and 18S rRNA are differentially expressed
      in the brain specimens of both AD and control subjects, while GAPDH is similarly
      expressed in AD and control brain specimens. These findings suggest that GAPDH
      can be used as a endogenous reference gene in the study of AD brains. A
      comparative gene expression analysis also suggests that synaptophysin is down
      regulated in AD brain specimens compared to control brain specimens.

PMID- 14687680
TI  - Single-stage tracheal resection for severe tracheal stenosis in older children.
AB  - OBJECTIVE: While tracheal resection for management of tracheal stenosis is an
      effective technique that has been well described in adults, the results in
      children have been less encouraging, as children tolerate anastomotic tension
      less well than adults. We describe our current technique for the management of
      severe tracheal stenosis in older children. METHODS: Four teenagers, 16-17 years
      of age, presented with severe tracheal stenosis. A 16-year-old girl had sustained
      tracheal stenosis following prolonged intubation, and presented with a severe
      Grade III stenosis having had 25 endoscopic procedures, and a failed resection at
      another institute. Two 17-year-old boys and a 17-year-old girl presented with
      Grade IV stenosis at the suprastomal area following previous intubation injuries.
      All four children had an identical procedure with tracheal resection over a Hood
      tracheal stent. RESULTS: All four children were extubated in the operating room.
      Chin-to-chest sutures were removed between 7 and 10 days, as was the Hood stent.
      All four are currently asymptomatic with no airway stenosis. CONCLUSIONS:
      Although tracheal resection for tracheal stenosis in children is associated with
      a higher failure rate than is seen in the adult population, even severe stenosis
      and long segment resection may achieve excellent results. We feel that important
      factors influencing outcome in this series included anastomosis to an intact
      cricoid ring, and support of the anastomosis with a tracheal stent.

PMID- 14687681
TI  - Efficacy of adenoidectomy in the treatment of nasal and middle ear symptoms in
      children with Down syndrome.
AB  - OBJECTIVE: To compare the efficacy of adenoidectomy in children with Down
      syndrome and control patients. METHODS: Medical records were reviewed for
      preoperative symptoms, ear complaints, date and reason for adenoidectomy, and
      postoperative symptoms in 27 children (mean age, 6.0 years; range, 1.6-14.5
      years) with Down syndrome and 53 age- and sex-matched controls who had
      adenoidectomy between January 1978 and September 1997. Long-term follow-up was
      aided by telephone interviews. Improvement in nasal and middle ear symptoms after
      adenoidectomy was calculated as the percentage of patients symptom-free
      postoperatively among those with symptoms preoperatively. RESULTS: After
      adenoidectomy, more controls than patients with Down syndrome had improvement in
      symptoms, including nasal obstruction (86.7% versus 50.0%; P=0.005); snoring
      (73.2% versus 40.9%; P=0.01); mouth breathing (84.1% versus 40.9%; P<0.001); and
      middle ear disease (68.0% versus 23.1%; P<0.001). Patients with Down syndrome
      were 7.7 times (95% confidence interval, 2.3-25.3) more likely to have chronic
      ear drainage after adenoidectomy. CONCLUSIONS: The results of the study suggest
      that the efficacy of adenoidectomy in children with Down syndrome is
      significantly less than that in controls and should influence surgical decision
      making in these children.

PMID- 14687682
TI  - Simple method of vocal cord lateralization in bilateral abductor cord paralysis
      in paediatric patients.
AB  - OBJECTIVE: To simplify the procedure of suture lateralization of a vocal cord in
      children with bilateral abductor cord palsy and to evaluate its results. METHODS:
      Ten tracheostomised infants and children with bilateral abductor cord palsy where
      there was either minimal or no recovery of vocal cord movement even after 2
      years' observation were taken up for suture lateralization of one vocal cord. In
      this simplified procedure needles were passed twice through the larynx from one
      side of neck to the other. The aim was to reduce the microlaryngoscopic or
      telescopic manipulation inside the small larynx. Two techniques (1 and 2) were
      used to carry out this procedure. In technique 1 the needle used was one with a
      slit in the eye situated at its tail end whereas in technique 2 it was a lumbar
      puncture needle. Patient follow-up ranged from 6 months to 5 years. RESULTS:
      Intraoperative manipulation inside the larynx was considerably reduced. The
      technique 2 was even simpler and faster than technique 1. With both techniques
      the placement of suture was accurate without any knot inside the larynx. All the
      patients could be decanulated with only minimal stridor on exertion in two and an
      acceptable voice in all. CONCLUSIONS: Suture lateralization of one vocal cord
      using technique 2 can be tried as the first line of management in cases of
      bilateral abductor cord palsy requiring lateralization.

PMID- 14687683
TI  - Endoscopic-assisted midfacial degloving approach for type III juvenile
      angiofibroma.
AB  - BACKGROUND: Open surgery is the mainstay treatment for juvenile angiofibromas
      (JAF). Midfacial degloving approach provides good exposure to the target area
      with excellent cosmoses. Endoscopic techniques have been used for the removal of
      some small JAF. OBJECTIVES/HYPOTHESIS: To evaluate the efficacy and outcome of
      endoscopic-assisted midfacial degloving approach as a route for removal of type
      III juvenile angiofibroma. PATIENTS AND METHODS: Fifteen young male patients with
      type III JAF (based on Fisch classification by computed tomography (CT) and
      magnetic resonance imaging (MRI) or both), were operated on by endoscopic
      assisted midfacial degloving approach. Pre-operative angiography and embolization
      were performed in two patients. The surgical technique is described in details.
      RESULTS: Apart from a case developed cerebrospinal fluid (CSF) rhinorrhea
      intraoperatively there were neither major operative nor post-operative
      complications. CSF leak was repaired through the same approach successfully in
      the same set. Thirteen patients had complete tumor clearance with no residual or
      recurrence during the follow-up period which ranged from 6 months to 6 years.
      Recurrence was detected early by endoscopic examination in two cases (3 and 8
      months post-operatively) and confirmed by CT and MRI. Endoscopic transnasal
      removal of the recurrent JAF was done successfully under local anesthesia in the
      first patient and under general anesthesia in the second with no recurrence
      during the follow-up period. CONCLUSIONS: Endoscopic-assisted midfacial degloving
      approach for removal of type III JAF enables the surgeon to gain the advantages
      of midfacial degloving approach with extensive exposure of the surgical field.
      Employing an endoscope, offers safe dealing with serious intraoperative
      complications like CSF leak. Post-operative follow-up by endoscopic nasal
      examination can detect early recurrence, which can be confirmed by CT and MRI.

PMID- 14687684
TI  - International perspectives on management of acute otitis media: a qualitative
      review.
AB  - BACKGROUND: Current opinions regarding the management of acute otitis media (AOM)
      in children vary across Western countries. With antibiotic resistance rising and
      more evidence regarding the limited clinical efficacy of antibiotics becoming
      available, interest in managing AOM other than with antibiotics is renewed.
      OBJECTIVES: To compare international rates of antibiotic prescription and surgery
      for AOM. To provide current evidence regarding the efficacy of various treatment
      options for AOM and their potential complications. METHODS: Qualitative
      (narrative) review. RESULTS: The percentage of patients given antibiotics for AOM
      varies from 31% in The Netherlands to more than 90% in most other Western
      countries. The 1998 prevalence of penicillin-resistant S. pneumoniae strains, on
      the other hand, ranges from 3% in The Netherlands to 53% in France. The surgical
      rate for tympanostomy tubes varies from 2 per 1000 children per year in the
      United Kingdom to 20 per 1000 in The Netherlands. The benefit of both antibiotic
      and surgical therapy in AOM appears to be limited, with numbers needed to treat
      ranging from 8 to 25 for antibiotic therapy, depending on the definition of
      outcome. CONCLUSIONS: International rates of antibiotic prescription and surgery
      for AOM vary strongly, which can be explained largely by the lack of uniform
      evidence-based guidelines. International debates with the aim of overcoming
      cultural differences regarding the management of otitis media, and of reaching
      agreement on guidelines on the basis of current evidence are necessary.

PMID- 14687685
TI  - Peripheral glycerol injection for the relief of facial neuralgia in children.
AB  - OBJECTIVE: In order to evaluate the therapeutic value of peripheral glycerol
      injection (PGI) in children with trigeminal neuralgia (TN). METHODS: A total of
      18 sick chlordane with TN have been treated by PGI with a follow-up period
      ranging from 2.5 to 3.6 years. RESULTS: It is shown that the result is excellent
      in 72.2%, good in 11.1%, poor in 11.1%, and 22.2% had a recurrence. Of them, 16
      of the original patients experienced a satisfactory control of pain following
      PGI, which produced no changes of the facial sensibility. CONCLUSION: This report
      indicates that it is a less formidable procedure, simple to perform and easily
      repeated so remains the choice for the majority of sick children with intractable
      TN, along with the additional benefit of no risks of facial sensory loss when
      compared to that of classic neuroectomy.

PMID- 14687686
TI  - Management of anomalies of the third and fourth branchial pouches.
AB  - Third and fourth branchial pouch anomalies are rare and usually present as
      lateral neck masses, abscesses or with acute suppurative thyroiditis. An opening
      in the piriform sinus can be identified in most cases. We present four cases of
      fourth branchial pouch sinuses, one of a third branchial cyst and discuss our
      management. Cannulation of the sinus tract at laryngoscopy, followed by complete
      surgical excision, via a modified oblique thyrotomy above the cricothyroid joint
      after detaching the inferior constrictor was used to treat the fourth branchial
      pouch anomalies. This surgical approach adequately exposes the piriform sinus
      apex and also affords protection to the recurrent laryngeal nerve. The third
      pouch cyst and tract were excised at the level of the thyrohyoid membrane. There
      were no complications or recurrences.

PMID- 14687687
TI  - Alloiococcus otitidis in acute otitis media.
AB  - OBJECTIVE: The bacterium Alloiococcus otitidis has been found to be associated
      with otitis media with effusion (OME). When the culture method is used, its
      detection rate is low, whereas applying the polymerase chain reaction (PCR)
      yields significantly higher frequencies. This study was carried out to
      investigate the incidence of A. otitidis in children with acute otitis media
      (AOM). METHODS: Multiplex PCR was used to detect A. otitidis together with
      Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae in
      the middle ear effusions (MEEs) of 118 children with AOM. The clinical outcome of
      AOM and the bacterial findings of MEEs were compared. RESULTS: A. otitidis was
      detected in 25% (30 of 118) of the tested MEE samples. Children over 2 years of
      age had significantly more often A. otitidis-positive MEEs (37%; 22 of 59) than
      younger children (14%; 8 of 59) (chi-square test, P<0.01). There were no
      significant differences in the duration, clinical failures (after antibiotic
      treatment), or number of recurrences of AOM between the A. otitidis-positive and
      A. otitidis-negative children. CONCLUSIONS: A. otitidis is found from the MEEs of
      AOM. The present data suggest that it has no clinical significance in AOM, and it
      does not increase the risk of developing OME after AOM.

PMID- 14687688
TI  - Effect of inhibitors of leukotriene and/or platelet activating factor on killed
      H. influenzae induced experimental otitis media with effusion.
AB  - Our previous studies have shown that leukotriene (LT) and platelet activating
      factor (PAF) are important inflammatory mediators (IMs) in the pathogenesis of
      otitis media with effusion (OME). The purpose of this study was to determine the
      effect of a LT-inhibitor and/or PAF-antagonist on experimentally induced OME by
      killed H. influenzae in chinchillas. LT-inhibitor SCH-37224 and/or PAF-antagonist
      WEB-2170 were systematically administered, each separately or in combination, 2h
      prior and then at regular intervals after the injection of killed H. influenzae
      into the superior bullae. After 48h, OME was completely prevented in the
      combination group while it was only partially prevented in the other two
      separately treated groups. Animals in the control group all developed OME.
      Findings of this study suggest the importance of LT and PAF in the pathogenesis
      of OME and the usefulness of their blockers in the prevention of OME suggesting
      possible future therapeutic implication.

PMID- 14687689
TI  - Surface electromyographic studies of swallowing in normal children, age 4-12
      years.
AB  - OBJECTIVES: Surface electromyographic (sEMG) studies were performed on 100 normal
      children, age 4-12 years, to establish normative database for duration and
      amplitude of muscle activity during swallowing and continuous drinking. STUDY
      DESIGN: Prospective observational study of healthy volunteers. METHODS:
      Parameters evaluated during swallowing include the timing and amplitude (in
      microV) of activity of m. orbicularis oris, masseter, submental and infrahyoid
      (laryngeal strap muscles (LSM)) groups covered by platisma. Four tests were
      examined: voluntary single swallows of saliva ("dry" swallow), voluntary single
      water swallows as normal, voluntary single swallows of excessive amount of water
      (up to 15ml), continuous drinking of 50ml of water (duration and number of
      swallows). Duration of muscle activity during swallowing (mean plus standard
      deviation (S.D.)) was measured for two age groups: 4-8 and 9-12 years old. The
      group of 40 adults, age 18-30 years, was taken as a control group. RESULTS:
      Normative data for duration and amplitude of muscle activity during single
      swallowing and continuous drinking are established for healthy children. The
      duration of muscle activity during swallows and drinking in all tests showed
      decrease with the age, and this tendency is statistically significant (one
      dimensional analysis of variance, SPSS, chi(2) criterion, 95% confidence
      interval). There was no statistically significant difference in amplitude (range)
      measurements between children and adults (P=0.05). There was no statistically
      significant difference between male and female children duration of muscle
      activity during single swallowing and continuous drinking in all age groups
      (P>/=0.05). CONCLUSION: Surface EMG of swallowing is a simple and reliable
      noninvasive method for screening evaluation of swallowing with low level of
      discomfort of the examination. The normative timing of events data can be used
      for evaluation of complaints and symptoms, as well as for comparison purposes in
      pre- and postoperative stages and in electromyography (EMG) monitoring during ENT
      or neurological treatment. These parameters represent normal deglutition, and can
      be used to identify abnormalities in pediatric patients, and provide a basis for
      comparison of swallowing performance, both within and between patients.

PMID- 14687690
TI  - Naturalistic intervention in cleft palate children.
AB  - AIM: To compare two modalities of speech intervention (SI) in cleft palate
      children with compensatory articulation disorder (CAD). The first modality was a
      phonologic based intervention, the second modality was a naturalistic
      intervention. The main purpose was to study whether a naturalistic intervention
      may reduce the total time of speech therapy necessary for correcting CAD in cleft
      palate children as compared to a phonologic intervention. MATERIALS AND METHODS:
      A prospective, comparative, and randomized trial was carried out. Cleft palate
      children with velopharyngeal insufficiency and CAD were included in the study
      group. Only patients with an age ranging from 3 to 7 years were included. A total
      of 30 patients were selected and were divided randomly into two groups. Fifteen
      patients were included in the first group (control) and received phonologic SI.
      The other 15 patients were included in the second group (active) and received
      naturalistic SI. The speech pathologist in charge of the SI was the same in all
      cases. A blind procedure was utilized whereby each patient was evaluated
      independently by two speech pathologists every 3 months until both examiners were
      convinced that CAD had been completely corrected. The mean total time of SI
      required for the normalization of speech in the two groups of patients was
      compared. RESULTS: Median age in the control group was 54.5 months, and 57.5
      months in the active group. A Mann-Whitney rank sum test demonstrated a non
      significant difference (P=0.803). The mean total time of SI in the control group
      was 14.53, and 16.27 in the active group. A student's t-test demonstrated that
      the total time of SI was not significantly reduced (P=0.331) when a naturalistic
      intervention was utilized. CONCLUSIONS: Naturalistic based SI did not reduce the
      time necessary for correcting CAD in cleft palate children.

PMID- 14687691
TI  - Short ribosomal prophylaxis in the prevention of clinical recurrences of chronic
      otitis media in children.
AB  - The aim of this study was to compare the efficacy and the safety of a short oral
      ribosomal immunotherapy (Immucytal) in the prevention of chronic otitis media in
      children. Seventy-two patients were enrolled in this study, 41 males and 31
      females, aged between 6 and 14 years, with an history of recurrent otitis media.
      Patients were randomised to receive Immucytal (group A) or placebo (group B)
      according to the following protocol: one tablet daily in the morning 8 days per
      month for three consecutive months. Immucytal and placebo were identical in shape
      and size, in order to maintain double-blind conditions. The efficacy parameters
      were (evaluated before, at the end and 6 months after the beginning of the
      therapy): clinical score; changes in immunological parameters; patient's parents
      assessment of symptoms on a scale from 0 (much worse) to 4 (much improved) and
      hearing tests. Patients of group A, had an improvement of clinical items
      measured, serum concentrations of immunoglobulins, subjective patient's parents
      assessment of symptoms and hearing tests. For all evaluations, a significant
      difference between treatment groups was found. Using this dosage and posology
      (shorter than others) the beneficial effects of Immucytal were maintained until
      the end of the 6-month study period.

PMID- 14687692
TI  - Willingness-to-pay for pediatric cochlear implantation.
AB  - OBJECTIVE: This paper presents the results of the first willingness-to-pay (WTP)
      study to be undertaken on cochlear implantation. It aims to measure the values
      parents place on the UK having a pediatric cochlear implantation (PCI) programme.
      METHODS: Face-to-face semi-structured interviews were conducted with parents of
      children from the Nottingham Pediatric Cochlear Implant programme, whom had been
      implanted for a period ranging from 1 month to 13 years. Parents willingness-to
      pay for the UK to have a pediatric cochlear implantation programme were elicited
      using a bidding process question format and via a discrete choice question. To
      see if income was a significant determinant of willingness-to-pay an analysis of
      variance (ANOVA) was undertaken in the statistical package SPSS version 10.
      RESULTS: Two hundred and sixteen parents were interviewed over the period July
      2001-August 2002, representing over 130h of interviewing. The mean and median
      willingness-to-pay values elicited were UK pound 127 and 50 per month,
      respectively (UK pound 2001/2002). Willingness-to-pay was positively related to
      income (P<0.020). When the income constraint was removed, 99% of parents choose
      the implant over having the money the implant would cost to spend in some other
      way to benefit their child. CONCLUSIONS: Parents of implanted children were
      willing to pay substantial monthly amounts for pediatric cochlear implantation.
      Most parents saw no alternative to pediatric cochlear implantation that could
      improve their child's quality of life to the same extent. Willingness-to-pay was
      sensitive to income as expected suggesting that the values elicited are both
      valid and influenced by a respondent's budget constraint.

PMID- 14687693
TI  - Eustachian tube gland tissue changes are related to bacterial species in acute
      otitis media.
AB  - BACKGROUND AND OBJECTIVE: Prior investigations have shown that the number of
      mucus producing goblet cells in the middle ear and Eustachian tube (ET) mucosa is
      highly increased during and up to at least six months after experimental acute
      otitis media (AOM) caused by Streptococcus pneumoniae (SP). Further, the volume
      of the mucus producing paratubal gland components is increased up to 3 months
      after the acute infection. These changes may in conjunction with a deteriorated
      ET function predispose a subsequent development of secretory otitis media. The
      present investigation compares changes in goblet cell density and gland
      structures of the ET during and after AOM caused by various bacteria typically
      encountered in this disease, with emphasis on potential differences due to
      bacterial species. METHODS: Rat models of AOM caused by SP, non-typeable or type
      b Haemophilus influenzae (NTHI/HIB) or Moraxella catarrhalis (MC) were studied
      longitudinally up to 6 months after bacterial challenge. The ET was dissected and
      decalcified, paraffin embedded and serially sectioned, followed by PAS/alcian
      blue staining. The goblet cell density and the paratubal gland composition and
      volume were determined morphometrically in every 20th section, using a light
      microscope. RESULTS: Regardless of bacterial species, the ET goblet cell density
      was increased from day 8 and peaked day 16, followed by some degree of
      normalisation, although not reaching normal numbers within the 6 month period,
      except for MC. The highest increase was seen in AOM caused by the non-typeable
      Haemophilus strain, followed by HIB, SP and MC. Except with MC, pathological
      intra-epithelial glands formed and goblet cells were found in mucosal areas
      normally devoid of these. In all species but MC, the volume of the paratubal
      glands progressed to peak 16 days post-inoculation, followed by a gradual
      normalisation. The volume was still increased 3 months after the acute infection,
      but completely normalised after 6 months. The increase was primarily due to
      hypertrophy of the mucous gland components and highest in AOM caused by the
      Haemophilus species, followed by SP. CONCLUSION: The Eustachian tube goblet cell
      density is increased during and up to at least six months after AOM regardless of
      bacterial species, except when employing MC, by which the density was increased
      for a few weeks only. Except in AOM caused by MC, the volume of the ET glands
      increases during and up to at least 3 months after infection, primarily due to
      hypertrophy of the mucous gland components. The non-typeable Haemophilus strain
      induced the highest increase of both goblet cell density and mucous gland volume.
      The increased secretory capacity of the ET following AOM may by excessive mucus
      secretion contribute to the deteriorated ET function found after AOM and thus
      predispose, sustain or aggravate middle ear disease.

PMID- 14687694
TI  - Lingual tumors in infants: a case report and review of the literature.
AB  - Tumors of the tongue and the base of mouth are seen rarely in children. The
      incidence of the ones that are large enough to fill the oral cavity is especially
      low. If not recognized and treated, tongue tumors may obstruct the upper aero
      digestive tract and be fatal. A case of a huge lingual cystic tumor mimicking
      ranula, and obstructing the upper aero-digestive tract, which was diagnosed
      antenatal and treated during and after the delivery, is presented together with a
      review of the literature.

PMID- 14687695
TI  - Autologous mesenchymal stem cell transplantation induce VEGF and
      neovascularization in ischemic myocardium.
AB  - Neovascularization induced by vascular endothelial growth factor (VEGF)
      represents an appealing approach for treating ischemic heart disease. However,
      VEGF therapy has been associated with transient therapeutic effects and potential
      risk for hemangioma growth. Adult mesenchymal stem cells (MSCs) derived from bone
      marrow are a promising source for tissue regeneration and repair. In order to
      achieve a safe and persistent angiogenic effect, we have explored the potential
      of autologous MSCs transplantation to enhance angiogenesis and cardiac function
      of ischemic hearts. One week after myocardial infarction induced by occlusion of
      left anterior descending artery, autologous MSCs expanded in vitro was
      administrated intramyocardially into the infarct area of the same donor rats. By
      2 months, MSCs implantation significantly elevated VEGF expression levels,
      accompanied by increased vascular density and regional blood flow in the infarct
      zone. The neovascularization resulted in a decreased apoptosis of hypertrophied
      myocytes and markedly improved the left ventricular contractility (ejection
      fraction: 79.9+/-7.6% vs. 37.2+/-6.9% in control animals). Therefore, mechanisms
      underlying MSCs improvement of cardiac functions may involve neovascularization
      induced by differentiation of MSCs to endothelial cells and para-secretion of
      growth factors, in addition to the apoptosis reduction and previously reported
      cardiomyocytes regeneration. Two months after cell transplantation, there are
      significant improvement of left ventricular function. Hence, autologous MSCs
      transplantation may represent a promising therapeutic strategy free of ethical
      concerns and immune rejection, for neovascularization in ischemic heart diseases.

PMID- 14687696
TI  - Sensory circumventricular organs: central roles in integrated autonomic
      regulation.
AB  - Circumventricular organs (CVO) play a critical role as transducers of information
      between the blood, neurons and the cerebral spinal fluid (CSF). They permit both
      the release and sensing of hormones without disrupting the blood-brain barrier
      (BBB) and as a consequence of such abilities the CVOs are now well established to
      have essential regulatory actions in diverse physiological functions. The sensory
      CVOs are essential signal transducers located at the blood-brain interface
      regulating autonomic function. They have a proven role in the control of
      cardiovascular function and body fluid regulation, and have significant
      involvement in central immune response, feeding behavior and reproduction, the
      extent of which is still to be determined. This review will attempt to summarize
      the research on these topics to date. The complexities associated with sensory
      CVO exploration are intense, but should continue to result in valuable
      contributions to our understanding of brain function.

PMID- 14687697
TI  - Pachymedusa dacnicolor tryptophyllin-1: structural characterization,
      pharmacological activity and cloning of precursor cDNA.
AB  - Tryptophyllins are a heterogenous group of amphibian skin peptides originally
      identified in skin extracts of Neotropical leaf frogs, Phyllomedusa sp., by
      chemical means. Until now, biosynthetic precursor structure and biological
      activity remain unreported. Here we describe the isolation of a novel, post
      translationally modified tryptophyllin, Lys-Pro-Hyp-Ala-Trp-Val-Pro.amide (PdT
      1), from the skin secretion of the Mexican leaf frog, Pachymedusa dacnicolor.
      Using a 3'- and 5'-RACE strategy and an in vitro skin cDNA library, the PdT-1
      encoding precursor was cloned and found to consist of an open-reading frame of 62
      amino acids with a single copy of PdT-1 located towards the C-terminus. A
      synthetic replicate of PdT-1 was found to be a potent myoactive agent, relaxing
      mammalian arterial smooth muscle and contracting small intestinal smooth muscle
      at nanomolar concentrations. PdT-1 is thus the first amphibian skin tryptophyllin
      to be pharmacologically characterized and the first whose precursor cDNA has been
      cloned.

PMID- 14687698
TI  - Nutrient inhibition of ghrelin secretion in the fasted rat.
AB  - Ghrelin is a recently discovered stomach hormone whose secretion increases with
      fasting; the fasting-induced elevation is inhibited by refeeding. The aim of this
      study was to determine whether all nutrient types (i.e., carbohydrates, proteins,
      fats) and soybean trypsin inhibitor (SBTI), a secretagogue for intestinal
      cholecystokinin (CCK), given individually into the stomach or intravenously can
      inhibit ghrelin secretion in the fasted rat. Intragastric (i.g.) administration
      of intact protein, a protein digest, SBTI, dextrose, or fat decreased plasma
      ghrelin levels significantly (p<0.05). All nutrients inhibited ghrelin secretion
      equally. Fat and dextrose given intravenously (i.v.) also reduced ghrelin
      secretion. These data demonstrate that nutrients can inhibit ghrelin secretion by
      both the luminal and systemic routes. Additionally, the findings show that all
      nutrient types given orally are capable of inhibiting ghrelin secretion, and
      suggest that intestinal CCK may participate in the inhibition of ghrelin
      secretion following oral intake of nutrients.

PMID- 14687699
TI  - PLA2/PGE2 are involved in the inhibitory effect of bradykinin on the angiotensin
      (1-7)-stimulated Na(+)-ATPase activity of the proximal tubule.
AB  - Recently, we demonstrated that bradykinin (BK) counteracts the stimulatory effect
      of Ang-(1-7) on the Na(+)-ATPase activity from basolateral membrane of the
      proximal tubule through B2 receptor. In the present paper, the signaling pathway
      involved in the inhibitory response of the Na(+)-ATPase activity to BK was
      investigated. The following results indicate that the phospholipase A2
      (PLA2)/COX/prostaglandin E (PGE2) pathway is implicated in this process: (1) The
      inhibitory effect of BK on Ang-(1-7)-stimulated enzyme is abolished in a dose
      dependent manner by quinacrine (10(-9)-10(-6)M), a nonspecific PLA2 inhibitor,
      and by PACOCF3 (10(-7)M), an inhibitor of a Ca(2+)-independent PLA2. However,
      AACOCF3 (2 x 10(-4) M), an inhibitor of the cytosolic PLA2, does not modify the
      inhibitory effect of BK. (2) The inhibitory effect of BK on the Ang-(1-7)
      stimulated enzyme is reversed by cyclooxygenase (COX) inhibitors diclofenac (10(
      12) M) and indomethacin (10(-12) M). (3) PGE2 (10(-12)-10(-5) M) inhibits the
      Na(+)-ATPase activity in a dose dependent manner. (4)The inhibitory effects of
      PGE2 and BK on the Na(+)-ATPase activity are not cumulative. (5) PGE2 (10(-12)
      10(-8) M) counteracts the stimulatory effect of Ang-(1-7) on the enzyme activity
      in a dose-dependent manner.

PMID- 14687700
TI  - A corticotropin-releasing hormone antisense oligodeoxynucleotide reduces
      spontaneous waking in the rat.
AB  - We have previously hypothesized that corticotropin-releasing hormone (CRH) is
      involved in the regulation of physiological waking. In this study, we tested the
      hypothesis that reduction of CRH peptide would reduce spontaneous wakefulness of
      rats. We administered intracerebroventricularly into rats at several circadian
      time points antisense or sense DNA oligodeoxynucleotides (ODNs) corresponding to
      the initiation codon of CRH mRNA and determined subsequent effects on wakefulness
      and sleep of the rat. Our results indicate that CRH antisense
      oligodeoxynucleotides reduce spontaneous wakefulness during the dark (active)
      period, but not during the light (rest) period of the light/dark cycle. The
      alterations in time spent awake are due to reduced wake bout numbers, rather than
      a change in wake bout duration. These reductions in wakefulness were mirrored by
      increases in slow-wave sleep, while rapid eye movement sleep was not affected.
      Corticosterone, used as an index of CRH in the hypothalamus, was reduced by CRH
      antisense oligodeoxynucleotides during the same time that spontaneous wakefulness
      was reduced, suggesting CRH peptide modulation as the mediator of this response.
      In contrast, CRH sense oligodeoxynucleotides did not alter any parameter of this
      study during either the dark or light period. These findings provide additional
      support for the hypothesis that CRH is involved in the regulation/modulation of
      wakefulness.

PMID- 14687701
TI  - Involvement of atrial natriuretic peptide in blood pressure reduction induced by
      estradiol in spontaneously hypertensive rats.
AB  - The aim of the present study was to determine the involvement of atrial
      natriuretic peptide (ANP) in blood pressure (BP) alterations induced by estradiol
      treatment. Spontaneously hypertensive rats (SHR) and Wistar rats (WR) were
      ovariectomized and, after 3 weeks, were injected daily for 4 days with estradiol
      benzoate (E2; 5 microg/100 g/day) or a vehicle. One day after the last injection,
      the animals were decapitated, blood was collected, and both right and left atrial
      appendages were quickly removed for determination of ANP by radioimmunoassay
      (RIA), or used for ANP mRNA determination. Estradiol treatment induced a
      significant reduction of blood pressure in SHR, but not in WR. This reduction was
      correlated with the increase of plasma ANP levels that were significantly
      increased in E2-treated, compared with vehicle-treated, SHR. E2-treated SHR
      showed significant increases in ANP concentration in the right and left atria
      compared to the vehicle-treated animals. These observations were confirmed by ANP
      mRNA. In summary, the present study shows that short-term estradiol treatment
      reduces the blood pressure of ovariectomized SHR, but not of WR. This reduction
      was highly correlated with increased plasma estradiol and ANP levels. These
      results suggest that ANP is involved in mediating the effect of estradiol on
      blood pressure reduction.

PMID- 14687702
TI  - Localization of neuropeptide Y receptor Y5 mRNA in the guinea pig brain by in
      situ hybridization.
AB  - Neuropeptide Y (NPY) has prominent stimulatory effects on food intake in
      virtually all animals that have been studied. In mammals, the effect is primarily
      mediated by receptors Y1 and Y5, which seem to contribute to different aspects of
      feeding behavior in guinea pigs and rats/mice. Interestingly, differences in
      receptor distribution among mammalian species have been reported. To get a
      broader perspective on the role of Y5, we describe here studies of guinea pig
      (Cavia porcellus), a species which due to its phylogenetic position in the
      mammalian radiation is an interesting complement to previous studies in rat and
      mouse. Guinea pig brain sections were hybridized with two 35S-labeled
      oligonucleotides complementary to Y5 mRNA. The highest expression levels of Y5
      mRNA were observed in the hippocampus and several hypothalamic and brain stem
      nuclei implicated in the regulation of feeding, such as the paraventricular,
      arcuate and ventromedial hypothalamic nuclei. This contrasts with autoradiography
      studies that detected low Y5-like binding in these areas, a discrepancy observed
      also in rat and human. Y5 mRNA expression was also seen in the striatum, in great
      contrast to mouse and rat. Taken together, these data show that Y5 mRNA
      distribution displays some interesting species differences, but that its
      expression in feeding centers seems to be essentially conserved among mammals,
      adding further support for an important role in food intake.

PMID- 14687703
TI  - Ileal VIP submucous neurons: confocal study of the area enlargement induced by
      myenteric denervation in weanling rats.
AB  - Vasoactive Intestinal Peptide (VIP) neurons are maturing during suckling and
      weaning periods and the neuropeptide VIP is thought to be neurotrophic during
      ontogenesis. We have previously demonstrated that suckling rats with myenteric
      ablation have significantly higher mitotic index and an increase on villus height
      and crypt depth 15 days after treatment. In the current study, we measured the
      area of VIP neurons of submucous plexus in the ileum of weanling rats, in which
      myenteric neurons were ablated by serosal application of benzalkonium chloride
      (BAC). The area of VIP immunoreactive cell bodies, reconstructed under confocal
      microscope, was significantly increased in response to denervation. This result
      suggests that the myenteric plexus may have an inhibitory role over submucous
      plexus in the normal intestine. The enhanced production of VIP may be correlated
      with the increased epithelial proliferation induced by denervation in a critical
      period of life, from suckling to weaning time.

PMID- 14687704
TI  - Release of peptide YY by fat in the proximal but not distal gut depends on an
      atropine-sensitive cholinergic pathway.
AB  - Peptide YY (PYY) is released when PYY cells in short term culture are exposed to
      fat suggesting that this peptide may be released by fat in the distal gut without
      neural stimulation. PYY is also released by fat in the proximal 1/2 of small
      intestine. To test the hypothesis that the release of PYY by fat in the proximal
      but not distal intestine may depend on an atropine-sensitive, cholinergic
      pathway, PYY levels were compared in four dogs equipped with duodenal and mid
      intestinal fistulas when 60 mM oleate was perfused into either the proximal
      (between fistulas) or distal (beyond mid-intestinal fistula) 1/2 of gut at 2
      ml/min for 120 min with intravenous administration of saline or atropine. We
      found that, when fat was confined to the proximal 1/2 of the intestine, PYY
      release was reduced following intravenous atropine when compared with saline
      (p<0.01). However, when fat was confined to the distal 1/2 of the intestine, PYY
      release was not affected by the intravenous atropine. We conclude that PYY
      release by fat in the proximal but not distal intestine depends on an atropine
      sensitive, cholinergic pathway.

PMID- 14687705
TI  - Enhancement of a human immunodeficiency virus env DNA vaccine using a novel
      polycationic nanoparticle formulation.
AB  - In an effort to develop a more effective DNA immunization strategy for HIV, we
      synthesized an HIV-2 env DNA vaccine and delivered it in a novel polycationic
      adjuvant formulation that forms nanoparticles in solution and enhances protein
      expression. The polycationic adjuvant contained imidazole moieties to facilitate
      endosomal escape. Nanoparticles containing the DNA vaccine plasmid were formed by
      electrostatic condensation with the polycationic adjuvant. We hypothesized that
      this formulation would improve immune responses to the gp140 env gene from HIV
      2(UC2) by increasing the level of expressed antigen. We found that the
      nanoparticles were superior at inducing high levels of systemic antibody
      responses compared to naked DNA when delivered by the intradermal route in BALB/c
      mice. In addition, the nanoparticles induced higher levels of IgM, IgG, and IgA
      antibodies. These results suggest that nanoparticles may be an important adjuvant
      formulation to improve the effectiveness of genetic immunization and rationalize
      its use in the evaluation of vaccine candidates in non-human primate models for
      AIDS.

PMID- 14687706
TI  - Transcription and translation of the chemokines RANTES and MCP-1 in nasal polyps
      and mucosa in allergic and non-allergic rhinopathies.
AB  - The pathogenetic findings of rhinopathies show an increase in infiltrating cells
      including eosinophils. RANTES is a beta chemokine in which the cysteines are
      adjacent (C-C), and it attracts and activates eosinophil. We hypothesize that
      RANTES is locally produced within the nasal polyp microenvironment and is
      responsible for the inflammatory cell recruitment present in nasal polyposis. To
      test this hypothesis, we evaluated nasal polyps and mucosa from allergic and
      control, non-allergic patients for RANTES content. The relative levels of RANTES
      and MCP-1 protein in tissue homogenates were quantified using enzyme-linked
      immunosorbent assay technology, and quantitative reverse transcriptase-polymerase
      chain reaction (RT-PCR) tests for RANTES and MCP-1 mRNA expression were
      performed. The results indicate that RANTES expression and production increase in
      nasal mucosa (septal and turbinate portions) of allergic patients compared to the
      same mucosa in non-allergic patients. In allergic patients, RANTES levels of
      nasal polyp homogenates were nearly 12-fold higher than the RANTES levels in
      mucosa homogenate. In this study, we hypothesize that the particular anatomic
      structure and physiologic function of the turbinates are more involved in the
      pathogenesis of rhinitis and may undergo polypoid degeneration in allergic
      rhinitis than any other anatomical structure of the nose. Our data suggest that
      RANTES is more involved than MCP-1 in recruiting inflammatory cells in
      rhinological disease and may reflect the degree of local inflammation as
      consequence of the specific chemoattractant properties of RANTES. The level of
      RANTES in nasal polyps could be important in the development of the pathological
      state.

PMID- 14687707
TI  - Analysis of two T-cell receptor BV gene segment polymorphisms in caucasoid
      Brazilian patients with rheumatoid arthritis.
AB  - Considering the role of T-lymphocytes in rheumatoid arthritis (RA) and a possible
      involvement of the TCR in the pathology of this disease we analyzed allelic and
      genotypic frequencies of variants of two TCRBV gene segments (TCRBV3S1 and
      TCRBV18) in RA. A total of 95 caucasoid South Brazilian RA patients were
      genotyped for both TCRBV gene segment variants by restriction fragment length
      polymorphism preceded by PCR (PCR-RFLP) and the obtained frequencies were
      compared to those from healthy individuals. Allelic frequencies for the TCRBV3S1
      gene segment were, respectively, for RA patients and controls, 0.447 and 0.545
      (allele 1) and 0.553 and 0.455 (allele 2). Allelic frequencies for the TCRBV18
      gene segment were, respectively, for RA patients and controls, 0.824 and 0.806
      (allele 1) and 0.176 and 0.194 (allele 2). Neither allelic frequencies nor
      genotypic frequencies differ among RA and healthy individuals, suggesting that
      there is not a direct association among the TCRBV allelic variants studied and
      the development of RA and thus excluding the possibility of use of these gene
      segment polymorphisms as RA susceptibility markers.

PMID- 14687708
TI  - Anti-mycobacterial immunity induced by a single injection of M. leprae Hsp65
      encoding plasmid DNA in biodegradable microparticles.
AB  - A single sub-cutaneous injection of a plasmid DNA encoding a mycobacterial heat
      shock protein 65 (Hsp65) entrapped in biodegradable poly(lactic-co-glycolic acid)
      microspheres produced high titers of antibodies, measured 5 months after the
      injection in BALB/c mice. Splenocytes secreted IFN-gamma and exerted an anti
      bacterial effect on macrophages infected in vitro with Mycobacterium
      tuberculosis. The results are encouraging with regard to obtaining good
      compliance and vaccination coverage with candidate plasmid DNA vaccines,
      especially in developing countries.

PMID- 14687709
TI  - The role of mitochondria in nitric oxide-mediated thymocyte apoptosis.
AB  - The aim of this study was to analyze whether immunosuppressants could affect NO
      induced thymocytes apoptosis. S-Nitroso-N-acetyl-D,L-penicillamine (SNAP, an NO
      donor) has an apoptotic effect on murine thymocytes. This NO-induced thymocyte
      apoptosis is associated with a reduced uptake of DiOC(6), a fluorochrome which
      incorporates into cells depending on their mitochondrial membrane potential
      (DeltaPsi(m)). The immunosuppressant, cyclosporin A, partially inhibited NO
      induced thymocyte apoptosis as well as the reduction of DeltaPsi(m). In contrast,
      another immunosuppressant, FK506, did not affect NO-induced thymocyte apoptosis.
      Although FK506 and cyclosporin A inhibit T-cell signal transduction by the same
      mechanism, their effects on mitochondria may contribute to the differential
      apoptosis induction ability.

PMID- 14687710
TI  - Regulation of GRB2 and FLICE2 expression by TNF-alpha in rheumatoid synovium.
AB  - Chronic rheumatoid arthritis (RA) is characterized by the hyperplasia of synovial
      tissue, which results from dysregulation of proliferative and antiapoptotic
      signals transduced in the synovial cells by unknown mechanisms. To identify
      candidate factors involved in the regulation of synovial hyperplasia, the
      expression profile of 205 apoptosis-related genes was compared between tissues
      from patients with RA and osteoarthritis (OA) using a cDNA microarray.
      Upregulated genes in the RA synovium included TNFR2, FLICE2, and signaling
      molecules involved in a MAP kinase pathway (GRB2, MAPK p38). In contrast, genes
      encoding SARP1 and various cell cycle regulators were down-regulated in the RA
      synovium relative to OA. Importantly, the expression levels of GRB2 and FLICE2
      genes were remarkably enhanced in RA synoviocytes but not in OA synoviocytes in
      response to tumor necrosis factor (TNF)-alpha treatment. Thus, these results
      suggest that over-expression of GRB2 and FLICE2 in RA synovium is caused by TNF
      alpha inducibility differentially regulated in RA synoviocytes and provide
      potential pathogenic roles of these genes in the hyperplasia of the RA synovium.

PMID- 14687711
TI  - Antigen and glucocorticoid hormone (GC) induce positive selection of DP
      thymocytes in a TcR transgenic mouse model.
AB  - Thymocyte maturation in the thymus is controlled by stromal and humoral
      components. Among the humoral regulators locally produced glucocorticoids (GCs)
      seem to have a key role in the positive selection of thymocytes. Our previous
      studies have shown that the administration of GCs or the stimulation through the
      CD3 complex can induce apoptosis of double positive (DP) cells, but the combined
      presence of these stimuli induces positive selection. In this work our aim was to
      investigate the effects of antigen exposure and synthetic GC hormone
      (dexamethasone, DX) administration on the selection processes of DP cells in TcR
      transgenic mice. In our model, AND-pigeon cytochrome c (PCC)-specific I-E(k) (MHC
      II) restricted Vbeta3, Valpha11 TcR expressing transgenic mice were treated with
      PCC, with high or low dose DX, or with PCC and DX together, followed by the
      analysis of total thymocyte numbers, thymocyte composition, with regard to their
      CD69, Vbeta3 and Annexin V expression. The administration of PCC and/or DX for 2
      days resulted in a decreased DP cell number and a significantly increased CD4 SP
      cell ratio. However, in both cases the total thymocyte numbers decreased. CD69
      expression increased on both DP and CD4 SP cells after PCC and/or DX treatments.
      We found that after DX or combined treatment, the percentage of Annexin V
      positive cells increased. The ratio of Vbeta3 TcR bearing DP thymocytes showed no
      change after DX or PCC administrations alone, but it decreased significantly
      after combined treatment. MHC-II bound PCC peptides in the presence of GCs
      enhanced the maturation of Vbeta3+ DP cells into CD4 SP stage, therefore, the
      Vbeta3- cells remained mostly in the DP immature stage. These data indicate that
      both antigen and low dose GC alone are capable of inducing positive selection of
      DP cells, but together they gave a stronger effect in promoting positive
      selection. From these we conclude that GCs influence the maturation and selection
      processes of thymocytes.

PMID- 14687712
TI  - Natural mechanisms protecting against cancer.
AB  - Carcinogenesis is a multistage process. At each step of this process, there are
      natural mechanisms protecting against development of cancer. The majority of
      cancers in humans is induced by carcinogenic factors present in our environment
      including our food. However, some natural substances present in our diet or
      synthesized in our cells are able to block, trap or decompose reactive oxygen
      species (ROS) participating in carcinogenesis. Carcinogens can also be removed
      from our cells. If DNA damage occurs, it is repaired in most of the cases.
      Unrepaired DNA alterations can be fixed as mutations in proliferating cells only
      and mutations of very few strategic genes can induce tumor formation, the most
      relevant are those activating proto-oncogenes and inactivating tumor suppressor
      genes. A series of mutations and/or epigenetic changes is required to drive
      transformation of a normal cell into malignant tumor. The apparently unrestricted
      growth has to be accompanied by a mechanism preserving telomeres which otherwise
      shorten with succeeding cell divisions leading to growth arrest. Tumor can not
      develop beyond the size of 1-2mm in diameter without the induction of
      angiogenesis which is regulated by natural inhibitors. To invade the surrounding
      tissues epithelial tumor cells have to lose some adhesion molecules keeping them
      attached to each other and to produce enzymes able to dissolve the elements of
      the basement membrane. On the other hand, acquisition of other adhesion molecules
      enables interaction of circulating tumor cells with endothelial cells
      facilitating extravasation and metastasis. One of the last barriers protecting
      against cancer is the activity of the immune system. Both innate and adaptive
      immunity participates in anti-tumor effects including the activity of natural
      killer (NK) cells, natural killer T cells, macrophages, neutrophils and
      eosinophils, complement, various cytokines, specific antibodies, and specific T
      cytotoxic cells. Upon activation neutrophils and macrophages are able to kill
      tumor cells but they can also release ROS, angiogenic and immunosuppressive
      substances. Many cytokines belonging to different families display anti-tumor
      activity but their role in natural anti-tumor defense remains largely to be
      established.

PMID- 14687713
TI  - Involvement of MAP kinase signal transduction pathway in UVB-induced activation
      of macrophages in vitro.
AB  - Ultraviolet B (UVB) radiation causes a variety of biological effects that can be
      either beneficial or harmful for human health. To exert these effects on a
      cellular basis, UVB induces a variety of signaling pathways, which act in an
      independent and additive ways. However, the UVB-induced signal transduction
      mechanism(s) till date remains not well understood. In the current investigation,
      we demonstrate p42/44, p38 and JNK MAPK activation in murine peritoneal
      macrophages on irradiation with UVB as determined by the expression of phospho
      p42/44 MAPK, -p38 and -JNK. These responses were found to be rapid and time
      dependent, detectable as early as 5 min post UVB irradiation 50 mJ/cm(2) and
      reached a peak by 15 min. UVB-induced phosphorylation of p42/44, p38 and JNK
      MAPKs was found to be blocked by Galphai-protein inhibitor, pertussis toxin;
      tyrosine kinase inhibitor, genistein; and PI3-K inhibitor, wortmannin. The
      activation of downstream transcription factors, c-jun and c-fos was also observed
      in response to UVB irradiation. The role of PD98059, SB202190, genistein, and
      wortmannin in regulating UVB-induced c-jun and c-fos activation and transcription
      was also investigated. The functional consequences of UVB-induced p42/44 MAPK and
      p38 MAPK activity were studied using TNF-alpha and NO production in the
      macrophages. The data suggests the involvement of p42/44, p38 and JNK MAPK
      pathway and subsequent induction of c-fos and c-jun in the signal transduction
      process leading to the activation of macrophages exposed to UVB.

PMID- 14687714
TI  - Identification of a shared epitope recognized by melanoma-specific, HLA-A3
      restricted cytotoxic T lymphocytes.
AB  - We previously established a melanoma-reactive cytotoxic T lymphocyte (CTL) line
      that recognizes multiple epitopes in the context of HLA-A3. To increase the
      number of peptides available for use in a vaccine for the treatment of melanoma,
      we identified one of these epitopes, SQNFPGSQK, through a combination of epitope
      reconstitution experiments and mass spectrometry. The SQNFPGSQK peptide was also
      found to be associated with HLA-A3 on an additional melanoma tumor line, thus
      indicating that the peptide is not unique to the melanoma tumor line from which
      it was isolated and thus, unlikely to arise through a mutational event. Although
      the protein origin of SQNFPGSQK has yet to be established, the shared nature of
      this epitope and the fact that it elicits a natural immune response indicates
      that it warrants further study to determine its usefulness as a vaccine component
      for the treatment of melanoma. The peptide may also be useful as a research tool
      for evaluating spontaneous anti-tumor immune responses in patients with melanoma.

PMID- 14687715
TI  - Cross-talk between Fc receptors and integrins.
AB  - Fc receptors (FcRs) and integrins are both key players of immune responses. These
      receptors are capable of independent signaling that leads to various cell
      functions. Recently, it is becoming clear that these receptors are also capable
      of modulating each other's responses. This modulation is achieved by direct
      physical interactions of the receptors on the cell surface, or by one receptor
      modifying the signaling pathway of the other receptor. Receptor co-localization
      and resonance energy transfer studies have shown that Fc receptors and integrins
      interact on the cell surface. Biochemical and functional studies have shown that
      signaling from Fc receptors modulates integrin adhesiveness through a process
      called "inside-out signaling". Other studies also show that the signaling from
      integrins modulates Fc receptor responses such as adhesion to immune complexes
      and cell mediated antibody-dependent cytotoxicity. This bi-directional cross-talk
      between Fc receptors and integrins is very important for the final cell function.
      Here, we review the latest information about interactions between Fc receptors
      and integrins.

PMID- 14687716
TI  - Advances in vector-mediated gene transfer.
AB  - Clinical applications of gene transfer technology initially targeted the
      treatment of inherited monogenetic disorders and cancers refractory to
      conventional therapies. Today, gene transfer approaches are being developed for
      most tissues and for multiple disorders including those affecting quality of
      life. The focus herein is eventual application of gene transfer technology for
      the management of organ-directed autoimmunity. A specific example is presented:
      Sjogren's syndrome and localized salivary gland gene transfer. The status of
      relevant pre-clinical gene transfer studies is reviewed, with an emphasis on use
      of adenoviral and adeno-associated viral vectors. Current limitations of
      effective organ-directed gene transfer are also discussed.

PMID- 14687717
TI  - Cytochrome P450 1A1 and manganese superoxide dismutase genes polymorphisms in
      reactive arthritis.
AB  - To investigate the role of cytochrome P450 1A1 (CYP1A1) and manganese superoxide
      dismutase (Mn SOD) genes polymorphisms in the susceptibility to reactive
      arthritis, the polymorphisms of CYP1A1 and Mn SOD genes were determined in 43
      patients with reactive arthritis following Chlamydia trachomatis infection and 92
      healthy controls by polymerase chain reaction (PCR)/restriction fragment length
      polymorphisms (RFLP) method. The frequencies of CYP1A1 4887C/A and C/A+A/A were
      significantly higher in patients with reactive arthritis than in controls.
      Moreover, the increased frequency of CYP1A1 4887A in patients with reactive
      arthritis is independent of HLA-B27. The frequency of Mn SOD 1183T/T tended to be
      increased in patients with reactive arthritis. We also found that the frequency
      of CYP1A1 4887A was significantly increased in Mn SOD 1183T/T(+) reactive
      arthritis patients compared with 1183T/T(+) controls. CYP1A1 4887A may be a risk
      factor for the development of reactive arthritis, especially in the presence of
      Mn SOD 1183T/T.

PMID- 14687718
TI  - Adhesion molecule expression patterns indicate activation and recruitment of CD4+
      T cells from the lymph node to the peripheral blood of early cutaneous
      leishmaniasis patients.
AB  - Adhesion molecules play a crucial role in cell migration and recruitment.
      Expression of adhesion molecules that preferentially address cells to
      inflammatory sites is a critical event in the formation and maintenance of
      leishmaniasis lesions. In this work, we analyzed the expression of CD11a, CD11b
      and CD62L, adhesion molecules involved in cell activation and circulation, in
      CD4+ and CD8+ T cells from peripheral blood and lymph nodes of patients with
      early cutaneous leishmaniasis. The percentage of expression of CD62L, CD11a and
      CD11b in total lymphocytes was lower in lymph nodes as compared to peripheral
      blood. Moreover, differences in adhesion molecule expression between blood and
      lymph nodes were more striking in CD4+ than CD8+ T cells. Stimulation of PBMC
      from leishmaniasis patients with soluble Leishmania antigens (SLA) lead to the
      expansion of CD4+CD62Lhigh cells, CD4+CD11b+ cells and to an increase in the
      intensity of expression of CD11a in CD4+, but not CD8+ T cells. Our data suggest
      that early activation events that occur in the lymph nodes of patients recently
      infected with Leishmania lead to changes in T cell adhesion molecule expression,
      favoring migration to the periphery and increasing the likelihood of further
      recruitment to lesion sites.

PMID- 14687719
TI  - Vaccinia virus recombinant expressing gene of tick-borne encephalitis virus non
      structural NS1 protein elicits protective activity in mice.
AB  - A vaccinia virus recombinant containing the non-structural tick-borne
      encephalitis virus (TBEV) NS1 gene was developed. The recombinant expressed
      native dimeric form of the NS1 protein in infected cells and protected mice
      against lethal infection with TBEV.

PMID- 14687720
TI  - Neurotransmitters regulate the migration and cytotoxicity in natural killer
      cells.
AB  - Natural killer (NK) cells and cytotoxic T lymphocytes (CTL), the functional
      coordination of which are governed by various signal substances, are crucial in
      the body's defense of tumor and virus-infected cells. We investigated the role of
      various neurotransmitters and hormones on the regulation of functional
      parameters, including NK cell cytotoxicity, and the migration of NK cells and CTL
      within a three-dimensional collagen lattice. Using peripheral blood CTL and NK
      cells, we show that the neurotransmitters endorphin, histamine and substance P
      increase NK cell cytotoxicity, while norepinephrine inhibits cytotoxicity.
      Moreover, substance P reduces migratory activity, while norepinephrine increases
      NK cell and CTL migration. Furthermore, all three steroid hormones which were
      investigated, namely cortisone, testosterone, and estradiol, had regulatory
      influence on both cytotoxicity and migration of NK cells. These results further
      specify the functional basis of the complex interconnection between the immune
      and neuro-endocrine systems.

PMID- 14687721
TI  - The effects of ITIM-bearing FcgammaRIIB on the nuclear shuttling of MAP kinase in
      RBL-2H3 cells.
AB  - We have studied the effects of ITIM-bearing FcgammaRIIB2 on the FcepsilonRI
      dependent nuclear shuttling of mitogen-activated protein (MAP) kinase (ERK2) in
      rat basophilic leukemia (RBL-2H3) cells. The cross-linking of FcepsilonRI
      elicited the sustained increase of the intracellular calcium ion concentration
      ([Ca(2+)](i)) and the translocation of ERK2 from the cytoplasm to the nucleus.
      The import of ERK2 to the nucleus reached the maximum at 6-7 min, thereafter ERK2
      was exported within 30 min. The co-clustering of FcepsilonRI and FcgammaRIIB2
      increased the [Ca(2+)](i) and induced the import of ERK2. However, the calcium
      increase was transient and ERK2 was rapidly exported to the cytoplasm. In
      addition, the phosphorylation of ERK2 and the production of TNF-alpha were
      decreased in case of co-clustering of FcepsilonRI and FcgammaRIIB2. This
      suggested that the co-clustering negatively control the production of pro
      inflammatory cytokines through the suppression of nuclear shuttling of ERK2.

PMID- 14687722
TI  - MHC class I status of tumours and design of immunotherapeutic strategies.

PMID- 14687723
TI  - Classification of B-cells according to their differentiation status, their micro
      anatomical localisation and their developmental lineage.
AB  - B-lymphocytes or B-cells form a diverse and flexible repertoire of immune cells
      that are reactive to almost all potential pathogens by means of the production of
      antigen-specific immunoglobulins. They can be divided into different populations
      or subsets, characterised by a distinct combination of properties. These subsets
      are identified on the base of their differentiation status (precursor B-cells,
      peripheral B-cells), their localisation in the micro-anatomical compartments of
      the B-cell follicle (marginal zone B-cells, lymphocytic corona B-cells, follicle
      centre B-cells), and the developmental lineage to which they belong (B-1 cells,
      and B-2 or conventional B-cells). The latter classification of B-cells into B-1
      cells and B-2 cells is commonly followed by immunologists, mainly in the study of
      mice models, while pathologists and haematologists tend to use a terminology for
      B-cells which refers to their localisation in the micro-anatomical compartments
      of the B-cell follicle and/or differentiation status. In this review, we will
      discuss the various subsets of B-cells and point to the similarities between the
      various classification systems in use.

PMID- 14687724
TI  - A dual role for tumor-derived chemokine RANTES (CCL5).
AB  - To investigate the role of tumor-derived CCL5 (regulated upon activation, normal
      T cell expressed and secreted, RANTES) in tumor immunity we compared the T cell
      response to tumors derived from the 4T1 murine mammary carcinoma cell line that
      express different levels of CCL5. Tumors that expressed low levels of CCL5
      exhibited a decrease in the in vivo, but not the in vitro, growth rate. In
      conjunction with the decreased growth rate the tumors that produced lower levels
      of CCL5 contained a greater number of tumor infiltrating lymphocytes compared to
      tumors that express normal levels of CCL5. One explanation for these findings was
      that a reduction in tumor-derived CCL5 prevented the tumor-associated alteration
      in T cell chemotactic activity. Tumors expressing lower levels of CCL5 also
      elicited a greater tumor-specific T cell response as evident by examination of
      recently activated T cells from tumor-draining lymph nodes. However, despite the
      enhanced T cell response, tumors expressing low levels of CCL5 still grew slower
      than tumors expressing normal levels of CCL5 in SCID mice. These data are
      consistent with the ability of CCL5 to upregulate transcription of matrix
      metalloproteinase-9 (MMP9), which can contribute to angiogenesis and thus, foster
      growth in vivo. Consequently, these data indicate that tumor-derived CCL5 can
      inhibit the T cell response and enhance the in vivo growth of murine mammary
      carcinoma.

PMID- 14687725
TI  - Effects of conjugated linoleic acid on growth and cytokine expression in Jurkat T
      cells.
AB  - Conjugated linoleic acid (CLA) has shown beneficial properties in animal models
      including anti-cancer, anti-atherogenic and anti-diabetic effects, while
      contrasting immunological effects were reported. While its anti-inflammatory
      activity has been associated to inhibition of arachidonic acid biosynthesis and
      to peroxisome proliferator-activated receptors (PPARs) activity, the molecular
      pathways underlying its immunoenhancing activity are essentially unknown. The aim
      of our study was to examine whether CLA showed specific effects in vitro on a T
      cell model, represented by the Jurkat cell line. CLA was found non toxic for
      Jurkat in the range 50-200 microM, as assessed by LDH release; however,
      incubation with 50 microM CLA was associated to a significant inhibitory effect
      on cell proliferation. The analysis of IL-2 and IFN-gamma transcript levels,
      produced in stimulated Jurkat cells, showed an increased expression of both
      cytokines in CLA-treated cells. Interestingly, the increased induction of IL-2
      but not of IFN-gamma mRNA, could be suppressed by co-incubation with Go 6976, a
      protein kinase C (PKC) inhibitor. Co-incubation with superoxide dismutase (SOD)
      or N-acetyl-L-cysteine (NAC) restored the basal levels of RNA synthesis for both
      cytokines. Taken together, these results suggest a specific role for dietary CLA
      in the modulation of the immune response in a T cell line model that is mediated,
      at least in part, by PKC and through the production of oxidative molecules.

PMID- 14687726
TI  - Impaired antigen receptor induced calcium mobilization in a phospholipase C
      gamma1 deficient B cell line.
AB  - B lymphocytes express phospholipase C-gamma(1) (PLC-gamma(1)) and phospholipase C
      gamma(2) (PLC-gamma(2)) isozymes. However, the relative importance of these two
      isozymes in B cell signaling is not known. We report here the identification and
      analysis of a B cell line deficient in PLC-gamma(1). Mature splenic B lymphocytes
      and a panel of cell lines representing pre-B, immature and mature B cell stages
      expressed phospholipase C-gamma (PLC-gamma), but not the beta or delta isoforms
      of phospholipase C (PLC). While all the tested B cell lines and primary splenic B
      cells expressed PLC-gamma(1) and PLC-gamma(2) isozymes, the L1.2 B cell line
      exclusively expressed PLC-gamma(2), but not PLC-gamma(1) isozyme. The PLC
      gamma(1) deficient L1.2 B cells expressed levels of surface IgM comparable to
      that of PLC-gamma(1) positive 70Z/3 B cell line. However, stimulation through the
      antigen receptor induced Ca(++) response in 70Z/3, but not L1.2 B cells,
      suggesting a requirement for PLC-gamma(1) in antigen receptor induced Ca(++)
      signaling in these cells. The possible use for L1.2 cells in testing the
      regulation of PLC-gamma(1) and PLC-gamma(2) dependent calcium mobilization in B
      lymphocytes is discussed.

PMID- 14687727
TI  - Determination of CD59 protein in normal human serum by enzyme immunoassay, using
      octyl-glucoside detergent to release glycosyl-phosphatidylinositol-CD59 from
      lipid complex.
AB  - In this study we have optimised the enzyme immunoassay (ELISA) to quantify CD59
      antigen in human serum or plasma. The glycosyl-phosphatidylinositol (GPI)-linked
      form of CD59 is known to complex with serum high-density lipoprotein. For ELISA
      optimisation, therefore, we investigated the effect of detergents, added to the
      sample diluent, on the determined values of CD59. Values obtained in the presence
      of octyl-glucoside (OG) for 20 adults aged 18-35 years and 17 children 1-5 years
      old were, respectively, 33-119 ng/ml (mean +/- S.D.: 66+/-22 ng/ml) and 37-143
      ng/ml (76+/-33 ng/ml). These results were higher than those measured without OG
      and were in contrast with published results showing absence, or eight to nine
      times lower levels, of the protein in serum. A known range for serum
      concentrations of CD59 in healthy individuals will establish an important
      reference point for clinical work and for the investigation of diseases involving
      the complement membrane attack complex (MAC) and its regulation.

PMID- 14687728
TI  - Lipopolysaccharide preferentially induces 4-1BB ligand expression on human
      monocyte-derived dendritic cells.
AB  - Dendritic cells (DCs) represent a promising tool for immunotherapy. A key feature
      in their action is to provide co-stimulatory signals for full activation of T
      cells. In view of recent studies demonstrating the critical role of 4-1BB co
      stimulation in T cell response, it is of importance to optimize 4-1BB ligand (4
      1BBL) expression on human monocyte-derived DCs (MDDCs), the DC source of many
      clinical studies. In this study, two types of MDDCs, generated in granulocyte
      macrophage colony-stimulating factor and interleukin-4 (GM-CSF/IL-4-DCs) or in
      interferon-beta and IL-3 (IFN-beta/IL-3-DCs), were analyzed for 4-1BBL expression
      in response to several known DC activators. Immature MDDCs expressed 4-1BBLs at
      very low levels. Lipopolysaccharide (LPS) was the only activator that
      preferentially triggered 4-1BBL expression on either MDDCs, but 4-1BBL-positive
      cells were significantly more frequently observed on LPS-activated GM-CSF/IL-4
      DCs (30.2+/-2.6% versus 14.3+/-1.2%). Combinations of multiple activating signals
      did not bring about enhanced 4-1BBL stimulatory capacity. In addition, plasmid
      DNA transfection and necrotic cell pulsing of GM-CSF/IL-4-DCs for antigen loading
      also resulted in 4-1BBL up-regulation. However, in all circumstances, the induced
      4-1BBL levels were low in comparison with CD80 co-stimulatory molecule. Finally,
      by demonstrating LPS-matured GM-CSF/IL-4-DCs from sorted 4-1BBL(high) population
      augmented T cell expansion and survival, we propose that efforts are required to
      increase 4-1BBL levels on MDDCs achieved by current activation schemes.

PMID- 14687729
TI  - A biased Valpha24+ T-cell repertoire leads to circulating NKT-cell defects in a
      multiple sclerosis patient at the onset of his disease.
AB  - As natural killer T (NKT) cells have been implicated in the regulation of
      multiple sclerosis (MS), we investigated expression of the Valpha24JalphaQ
      canonical rearrangement in MS patients during relapses. We observed major changes
      in the entire blood Valpha24(+) T-cell repertoire. Seven of the eight patients
      showed a marked decrease in Valpha24(+) transcript number and a decrease in the
      diversity of the Valpha24(+) T-cell repertoire, with the exception of a few
      expanded clones. These perturbations, exacerbated in patient MS (A), led to
      circulating NKT cell defects.

PMID- 14687731
TI  - Obstetric implications of cocaine use in pregnancy: a literature review.

PMID- 14687732
TI  - Apolipoprotein E and cholesteryl ester transfer protein polymorphisms in normal
      and preeclamptic pregnancies.
AB  - OBJECTIVES: To evaluate the association of apolipoprotein (apo) E polymorphism
      and a cholesteryl ester transfer protein (CETP) polymorphism (CETP/TaqIB) with
      preeclampsia and with lipid/lipoprotein profile in pregnancy. MATERIALS AND
      METHODS: A group of 144 normal pregnant women (67 in the third trimester) were
      compared with 51 cases of preeclampsia in the third trimester of gestation. Apo E
      and CETP genotypes were determined by polymerase chain reaction-restriction
      fragment length polymorphism. Serum lipids, lipoproteins and apolipoproteins were
      evaluated using commercially available kits. LDL size was assessed by gradient
      gel electrophoresis. RESULTS: No differences were found in the distribution of
      subjects with respect to genotypes, in the apo E and CETP polymorphisms, between
      control and pathologic groups. In the third trimester of gestation (both control
      and case groups considered), apo E polymorphism, but not CETP polymorphism, was
      associated with different lipid and lipoprotein levels. Patients carrying the E2
      allele (E2+) presented with significantly lower values of LDL cholesterol (LDLc)
      compared with carriers of E4 (E4+) and E3/3 individuals. E2+ also presented with
      the highest triglyceride (TG) level, although this was not statistically
      significant. On the other hand, HDL cholesterol (HDLc) and apo A-I levels were
      significantly reduced in E4+, compared with E3/3. Furthermore, E4+ presented with
      the highest total cholesterol and LDL and therefore LDLc/HDLc and apo B/apo A-I
      ratios were significantly higher in this group compared with the other two.
      CONCLUSIONS: Neither of our candidate genes showed association with preeclampsia.
      However, apo E genotype was associated with changes in lipid and lipoprotein
      profiles in pregnant women.

PMID- 14687733
TI  - High-resolution 1H NMR spectroscopy of amniotic fluids from spina bifida fetuses
      and controls.
AB  - OBJECTIVE: To quantify proton containing metabolites by in vitro 1H NMR
      spectroscopy of amniotic fluids from fetuses with spina bifida and controls.
      STUDY DESIGN: Fourteen amniotic fluids from spina bifida fetuses and 18 controls
      were obtained. Concentrations of carbohydrates, organic acids and amino acids
      were determined. Multiple linear regression analysis was used to evaluate the
      data. RESULTS: At 15 and 39 weeks amenorrhea, the estimated median amniotic fluid
      concentrations of succinic acid and glutamine were significantly higher in the
      spina bifida group compared to controls, 37 and 64%, respectively. Whereas
      creatine and creatinine were significantly lower, 27 and 36%, respectively.
      Amenorrhea influenced the concentrations of most compounds with the exception of
      lactic acid. CONCLUSION: 1H NMR spectroscopy shows significantly higher succinic
      acid and glutamine concentrations in amniotic fluids derived from spina bifida
      fetuses compared with controls. A derangement in amino acid metabolism is
      suggested.

PMID- 14687734
TI  - Universal antenatal screening for syphilis: is it still justified economically? A
      10-year retrospective analysis.
AB  - OBJECTIVE: Because universal prenatal screening for syphilis has recently been
      called into question, we documented the development of syphilis in Austria and
      analysed the effectiveness of current antenatal syphilis screening practices.
      METHODS: The development of syphilis in Austria and Vienna was determined based
      on the data published by the Austrian Bureau of National Statistics (Statistik
      Austria) and the Vienna Health Authority (Gesundheitsamt Wien, MA15),
      respectively. The data obtained for Vienna were then compared with those for the
      remaining eight federal provinces. Also, we retrospectively analysed a total of
      34,312 sera obtained between 1988 and 1999 from women screened for syphilis at
      delivery at the laboratory of the Department of Dermatology, University of
      Vienna. Serological screening was done with both the Venereal Disease Research
      Laboratory (VDRL) and the Treponema pallidum haemagglutination (TPHA) assays.
      Finally, we determined the number of cases of congenital syphilis diagnosed in
      Vienna between 1988 and 1999. RESULTS: In the past 10 years, the annual number of
      reported syphilis cases has remained fairly constant. In 1999 and 2000, there
      were 8.1 and 11.0 notifications of syphilis per 100,000 inhabitants in the
      capital Vienna, compared with 0.7 and 0.9 in the remaining provinces with a
      mainly rural character. At delivery, there were 96 cases of maternal syphilis
      that were both TPHA- and fluorescent treponemal absorption (FTA-ABS)-reactive,
      corresponding to a seroprevalence of 2.8 per 1000 births. Only 24 of the TPHA
      reactive sera were VDRL-reactive. In Vienna, there were three stillbirth
      deliveries due to congenital syphilis and six cases of confirmed congenitally
      syphilis between 1988 and 1999. CONCLUSION: Universal syphilis screening may no
      longer be justified economically. The usefulness of VDRL-based syphilis screening
      should be reassessed. The screening focus should shift to regions with a high
      seroprevalence of syphilis. Universal syphilis screening does not appear
      warranted.

PMID- 14687735
TI  - Qualitative study of perinatal care experiences among Somali women and local
      health care professionals in Norway.
AB  - OBJECTIVE: To explore how perinatal care practice may influence labor outcomes
      among circumcised women. STUDY DESIGN: In-depth interviews were conducted with 23
      Somali immigrants and 36 Norwegian health care professionals about their
      experiences from antenatal care, delivery and the management of circumcision.
      RESULTS: Circumcision was not recognized as an important delivery issue among
      Norwegian health care professionals and generally the topic was not addressed
      antenatally. The Somalis feared lack of experience and sub-optimal treatment at
      delivery. All of the women expressed a strong fear of cesarean section. Health
      care professionals were uncertain about delivery procedures for infibulated women
      and occasionally cesarean sections were performed in place of defibulation.
      CONCLUSION: We hypothesize that neglect of circumcision may lead to adverse birth
      outcomes including unnecessary cesarean sections, prolonged second stage of labor
      and low Apgar scores. We suggest that infibulated women need a carefully planned
      delivery, correctly performed defibulation and adequate pain relief.

PMID- 14687736
TI  - Premature rupture of membranes and early mortality among triplets in the United
      States.
AB  - OBJECTIVES: We investigated the relationship between premature rupture of the
      membranes (PROM) and early mortality among triplets in the United States. STUDY
      DESIGN: Analysis was conducted on matched and linked triplet sets born to mothers
      in the United States between 1995 and 1997. The generalized estimating equation
      framework was used to generate odds ratios after capturing the effects of sibling
      correlations within triplet clusters. RESULTS: Triplets exposed to PROM were
      twice as likely to experience stillbirth (OR=2.17, 95% CI [1.26-3.41]), neonatal
      death (OR=2.23, 95% CI [1.70-3.0]) and infant death (OR=2.21, 95% CI [1.72
      2.85]), as compared to those who did not. The population-attributable risk for
      early mortality due to PROM was 11-12%. CONCLUSIONS: Triplets associated with
      PROM had a significantly higher level of early mortality than those without.
      Assuming a causal relationship, 11-12% of all early deaths among triplets in the
      United States are accounted for by PROM.

PMID- 14687737
TI  - Maternal admission characteristics as risk factors for preterm birth.
AB  - OBJECTIVE: The aim of this study is to identify a subset of women presenting with
      preterm labor not responding upon tocolytic therapy, eventually resulting in
      preterm birth. STUDY DESIGN: The maternal admission characteristics of 185 women
      with preterm labor receiving tocolysis were analysed for risk factors that could
      predict which women will deliver within 48 h after the start of tocolysis, or
      before 34 weeks gestation. Univariate analysis and multivariate logistic
      regression analysis was performed. RESULTS: Logistic regression analysis
      identified the following risk factors for delivery within 48 h after the start of
      tocolysis: cervical dilatation at admission (odds ratio (OR, cm(-1)) 1.47; 95%
      confidence interval (CI), 1.44-1.49), elevated leukocyte count at admission (per
      10(3) leukocytes/mm(3)) (OR 1.27; 95% CI, 1.26-1.28), use of nifedipine (OR 0.49;
      95% CI, 0.26-0.49), and developing signs suggestive of chorioamnionitis following
      admission (OR 2.12; 95% CI, 1.04-4.33). For delivery before 34 weeks of gestation
      the following risk factors were identified: use of steroids (OR 5.87; 95% CI,
      2.34-14.7), use of nifedipine (OR 0.46; 95% CI, 0.27-0.85), developing signs
      suggestive of chorioamnionitis following admission (OR 10.6; 95% CI, 3.1-35.9),
      and preterm premature rupture of the membranes (OR 12; 95% CI, 4.1-35.2).
      CONCLUSIONS: Risk factors associated for delivery within 48 h after starting
      tocolysis are: cervical dilatation at admission, elevated leukocyte count at
      admission, and developing signs suggestive of chorioamnionitis following
      admission. Use of nifedipine was associated with a delay of delivery >48 h. Risk
      factors associated for delivery within 34 weeks gestation are: use of steroids,
      developing signs suggestive of chorioamnionitis following admission, and ruptured
      membranes. Use of nifedipine was associated with a delay >34 weeks.

PMID- 14687738
TI  - Can the reproducibility of fetal heart rate baseline estimation be improved?
AB  - OBJECTIVE: To evaluate the reproducibility of fetal heart rate (FHR) baseline
      estimation according to an objective and detailed definition presented in this
      article, by comparison with the FIGO guidelines' definition. STUDY DESIGN: Three
      hundred consecutively acquired FHR tracings, 150 from antepartum high-risk
      pregnancies and 150 from unselected intrapartum cases, were presented to nine
      experienced clinicians included in three different groups, for an estimation of
      the FHR baseline. The first group consisted of clinicians using the proposed
      definition, without previous training in its use. The second group consisted of
      clinicians using the proposed definition, where a previous training session was
      promoted. The third group consisted of clinicians using the FIGO guidelines'
      definition. Agreement in baseline estimation was evaluated using the kappa
      statistic, the proportions of agreement and the intra-class correlation
      coefficient. RESULTS: Using the baseline definition proposed in this article,
      agreement was significantly higher in the group with prior training in its use.
      This group also showed a trend towards a higher agreement than the one using the
      FIGO guidelines. CONCLUSION: The FHR baseline definition proposed in this article
      provides an extremely reproducible estimation when associated with prior training
      in its use.

PMID- 14687739
TI  - Effect of electromagnetic field emitted by cellular phones on fetal heart rate
      patterns.
AB  - The study was planned to determine the effects of electromagnetic fields produced
      by cellular phones on baseline fetal heart rate, acceleration and deceleration.
      Forty pregnant women undergoing non-stress test were admitted to the study. Non
      stress test was obtained while the subjects were holding the CP on stand by mode
      and on dialing mode, each for 5 min. Similar recordings were taken while there
      were no phones around for 10 min. Electromagnetic fields produced by cellular
      phones do not cause any demonstrable affect in fetal heart rate, acceleration and
      deceleration.

PMID- 14687740
TI  - Does manual removal of the placenta affect operative blood loss during cesarean
      section?
AB  - OBJECTIVE: To investigate whether manual removal of the placenta is associated
      with significantly more blood loss compared to spontaneous separation of the
      placenta during cesarean section. STUDY DESIGN: This was a randomised study of
      200 women with normal pregnancies undergoing cesarean section. Patients were
      randomly assigned to the study group, manual removal (n=100) or the control
      group, spontaneous separation (n=100). Operative blood loss was measured using a
      volume and gravimetric method. Patients postoperative complications were recorded
      and hemoglobin levels measured at 24 and 48 h. RESULTS: The amount of blood loss
      associated with spontaneous and manual removal of the placenta was 626+/-253 ml
      and 589+/-272 ml, respectively. This difference was not significant. There was a
      decrease in the postoperative hemoglobin levels in both groups which was not
      significantly different. The incidence of endometritis, wound infection, and the
      need for blood transfusion was similar in the two groups. CONCLUSION: Manual
      delivery of the placenta is not associated with a significantly greater risk of
      operative blood loss, decreased postoperative hemoglobin levels or increased
      incidence of endometritis compared with spontaneous placental separation.

PMID- 14687741
TI  - Criteria for transfusion in severe postpartum hemorrhage: analysis of practice
      and risk factors.
AB  - OBJECTIVE: To analyze the accuracy of postpartum hemorrhage risk factors to
      determine patients at risk of severe postpartum hemorrhage and transfusion.
      POPULATION AND METHODS: Retrospective cohort study from a database in one high
      risk obstetric unit over a 7-year period. RESULTS: In a cohort of 19,204
      deliveries, 44 patients were transfused of whom five were given frozen fresh
      plasma only. Of the 39 who received red blood cells, 35 received at least three
      units. Multivariate analysis of postpartum hemorrhage risk factors revealed a
      significant role of placenta previa/accreta, cesarean section, multiple
      pregnancy, prematurity and vascular disease. Nevertheless 28% of women transfused
      had none of these risk factors. CONCLUSION: The percentage of patients transfused
      has probably decreased markedly with improved prevention, surveillance and
      treatment. This study emphasizes that the transfusion risk in the presence of
      anomalous placental insertion justifies special obstetrical and anesthetic
      management.

PMID- 14687742
TI  - Dose of GnRH agonist (nafarelin acetate) affects intrafollicular PAPP-A
      expression in controlled ovarian hyperstimulation cycle.
AB  - OBJECTIVE: To determine the effect of dose of GnRH agonist on the follicular
      environment in controlled ovarian hyperstimulation (COH) cycles. STUDY DESIGN:
      Twenty-eight IVF patients with normal ovarian function were divided into three
      groups: group I received GnRHa (nafarelin acetate/Synarel) intranasally at 200
      microg daily, group II received 400 microg daily until hCG injection, and group
      III was given 400 microg daily before the initiation of ovarian stimulation, then
      200 microg daily before the day of hCG injection. Serum estradiol, progesterone,
      and leptin levels were measured on the day of hCG injection. After aspiration,
      expression of pregnancy-associated alpha-plasma protein (PAPP)-A in the
      follicular fluid of dominant follicles (>20 mm) was determined by Western blot
      analysis. RESULTS: No significant difference was noted in serum estradiol,
      progesterone, and leptin levels. But intrafollicular PAPP-A expression was
      significantly higher in group II compared to other groups (P<0.05). CONCLUSION:
      The dose of GnRHa may have an impact on the intrafollicular environment of
      dominant follicles in COH cycles.

PMID- 14687743
TI  - Leukaemia inhibitory factor (LIF) gene mutations in women with unexplained
      infertility and recurrent failure of implantation after IVF and embryo transfer.
AB  - OBJECTIVE: Leukaemia inhibitory factor (LIF) plays a central role in the control
      of implantation. We undertook this study to investigate the prevalence of LIF
      gene alterations in women with unexplained infertility and with recurrent failure
      of implantation after in vitro fertilisation (IVF) and embryo transfer. PATIENTS
      AND METHODS: Forty five women with recurrent failure of implantation after IVF
      (group A), 50 with unexplained infertility (group B) and 105 fertile women
      (controls) were screened for LIF gene mutations. Standard genomic DNA extraction,
      PCR amplification of the LIF gene and single-strand conformation polymorphism
      (SSCP) analysis were used to search for mutations which were subsequently
      confirmed by DNA sequencing. RESULTS: In group A, one woman was identified as
      having a neutral LIF gene polymorphism in exon 3 without affecting protein
      conformation. In group B, one woman with a heterozygous mutation and one with a
      neutral polymorphism were detected. In controls, only one woman with a neutral
      polymorphism in the intron between exons 2 and 3 was found. The woman with a
      potentially functional LIF gene mutation in group B achieved an ongoing clinical
      pregnancy after ovarian superovulation. DISCUSSION: Potentially functional
      mutations in the LIF gene do infrequently occur in women with unexplained
      infertility and may play a role in the etiology of infertility. However, routine
      screening for LIF mutations or polymorphisms in these women is not justified for
      the low prevalence of gene alterations.

PMID- 14687744
TI  - Effect of hormone replacement therapy and tibolone on serum total homocysteine
      levels in postmenopausal women.
AB  - OBJECTIVE: To assess the effect of continuous combined hormone replacement
      therapy (HRT) or tibolone on serum total homocysteine (tHcy) levels in
      postmenopausal women. STUDY DESIGN: Ninety-five postmenopausal women aged 41-68
      years were included in the study. Seventy-three women with climacteric
      complaints, osteopenia or osteoporosis received either conjugated equine
      estrogens 0.625 mg combined with medroxyprogesterone acetate 5 mg (CEE/MPA, n=31)
      or tibolone 2.5 mg (n=42). Twenty-two healthy women, matched for chronological
      and menopausal age, served as controls. Serum tHcy levels were assessed at
      baseline, 6, 12 and 18 months. RESULTS: No difference was recorded between groups
      regarding demographic characteristics or mean baseline serum tHcy. Serum tHcy
      levels decreased significantly in the CEE/MPA compared to baseline (change at 18
      months: -3.9%, P<0.05). The magnitude of the decrease was higher in the subgroup
      of women with baseline tHcy levels above the median (change at 18 months: -15.0%,
      P<0.01). No change in tHcy levels was detected in the tibolone group throughout
      the study period, either in the whole group (change at 18 months: 1.9%, NS) or in
      the subgroup with baseline tHcy levels above the median (change at 18 months: 
      3.23%, NS). CONCLUSION: Continuous CEE/MPA reduces tHcy especially in women with
      high pretreatment tHcy levels. Tibolone has no effect on serum tHcy levels at
      least during the first 18 months of therapy. Larger studies with longer follow-up
      are required to confirm these results.

PMID- 14687745
TI  - Contraceptive behaviour of teenagers requesting abortion.
AB  - OBJECTIVE: To examine the contraceptive use of teenage girls requesting abortion.
      STUDY DESIGN: A questionnaire survey was made concerning contraceptive use,
      awareness and the attitude toward contraceptives. The Mantel-Haenszel test was
      applied to compare contraceptive determinants between teenagers (<20 years old)
      and older women. RESULTS: The use of reliable contraceptive methods was
      significantly less frequent among the teenagers than among the older
      counterparts, but this difference was much more significant (P<0.001) between
      those who requested abortion (OR=0.44) than between the controls (OR=0.51). The
      knowledge about emergency contraceptive pills was similarly significantly poorer
      between the teenagers in the abortion group (P<0.001) relative to the older women
      (OR=0.07) and the teenagers in the control group (OR=0.10). Financial means was
      not a significant determinant in the choice of contraceptives. CONCLUSION: To
      prevent unwanted pregnancy among teenagers, the media, the family, the school and
      health-care providers should focus on sexual education and information.

PMID- 14687746
TI  - An evaluation of pelvic floor anatomy and function by MRI.
AB  - OBJECTIVE: In this experimental study, we wanted to evaluate the informative
      value of dynamic magnetic resonance imaging in pelvic floor anatomy during pelvic
      floor muscle contractions in asymptomatic women and women with urinary continence
      dysfunction. STUDY DESIGN: Eight outpatients with stress urinary symptoms and
      eight asymptomatic women were scanned with a 1.5 T GE Signa CV/i high-speed
      scanner with real time fluorescopic imaging possibilities. The static and dynamic
      anatomical status of the levator ani muscle was registered. RESULTS: In sagittal
      magnetic resonance imaging (MRI) images, the iliococcygeus muscle appeared as
      dome-shaped at rest. The thickness of the distal part of pubococcygeal muscle
      correlated significantly with EMG values during a maximal contraction. The most
      obvious defects seen in the pubococcygeal muscle were asymmetry in thickness and
      loss of fiber continuity. CONCLUSION: Functional and anatomic relationships in
      the pelvic floor can be demonstrated by the combined use of EMG and MRI,
      providing a better understanding of the pathophysiological mechanisms behind
      stress incontinence in women.

PMID- 14687747
TI  - A randomised trial of photographic reinforcement during postoperative counselling
      after diagnostic laparoscopy for pelvic pain.
AB  - OBJECTIVE: To measure the effect of seeing a photograph of the pelvic findings at
      laparoscopy. SETTING: Two university teaching hospitals. METHOD: A randomised
      controlled trial. SUBJECTS: Two hundred thirty-three women undergoing diagnostic
      laparoscopy for the investigation of chronic pelvic pain. INTERVENTIONS: At
      operation a Polaroid print was taken of the pelvis. If this was of satisfactory
      quality, the patient was randomly allocated to either see, or not see, the print
      during the postoperative consultation. MAIN OUTCOMES: Pain severity and pain
      belief scores at 3 and 6 months. ANALYSIS: By intention to treat. RESULTS:
      Postoperative consultations with photographs did not improve immediate
      understanding and satisfaction with the consultation. In addition, compared to
      controls, both patients and doctors did not perceive particular benefit for
      communication from the photograph. There was a consistent trend to more pain in
      the photographic reinforcement group and more negative pain beliefs. At 3 months,
      the average within person differences showed some benefit in visual analogue pain
      scores, McGill affect scores, 'permanence' and 'self-blame' scores. These
      benefits were not statistically significant. At 6 months, there was a consistent
      pattern of benefit from pain severity and pain beliefs, again these benefits were
      not statistically significant. CONCLUSION: No clear benefits result from showing
      patients photographs of their pelvis.

PMID- 14687748
TI  - How long should patients be followed after molar pregnancy? Analysis of serum hCG
      follow-up data.
AB  - OBJECTIVE: We analyzed human chorionic gonadotropin (hCG) follow-up data of
      patients with molar pregnancy. Women often do not complete recommended post
      disease screening. Our purpose was to determine if continuing follow up of
      uncomplicated molar cases beyond attaining undetectable hCG levels is necessary
      for detecting relapse of gestational trophoblastic disease. STUDY DESIGN: One
      hundred fifty patients treated at Hungarian National Health Center were analyzed.
      Those who developed persistent disease before hCG had become undetectable were
      excluded from further analysis (n=24; 16%). RESULTS: Among 126 uncomplicated
      cases, 72 patients (57%) completed follow up, and 54 (43%) discontinued their
      protocol before it had been completed. Of 120 patients who achieved at least one
      undetectable hCG level, none had any evidence of relapse. CONCLUSION: In
      uncomplicated hydatidiform mole, our analysis indicates that once undetectable
      serum hCG levels are attained, relapse is unlikely. Although further monthly
      checks are advisable, the likelihood of recurrence appears very low.

PMID- 14687749
TI  - Aspiration and alcohol sclerotherapy: a novel method for management of
      Bartholin's cyst or abscess.
AB  - OBJECTIVE: To investigate the efficiency and safety of alcohol sclerotherapy of
      Bartholin's cyst or abscess by comparing it with silver nitrate insertion. STUDY
      DESIGN: Twenty-two patients with unilateral Bartholin's cyst or abscess were
      randomized into one of the treatment groups according to diameter of cyst or
      abscess. Group I consisted of 12 patients who were treated with alcohol
      sclerotherapy and Group II included 10 patients who were treated with silver
      nitrate insertion. In both groups, treatments were conducted under local
      anesthesia and in an outpatient setting. The patients were checked for morbidity
      of operations every 3 days until complete healing was observed and then followed
      up monthly for over 24 months. RESULTS: The mean duration of procedure was 7+/-2
      min in group I and 15+/-3 min in group II. Healing time was 4.8+/-1.3 days in
      group I and 9.2+/-2.5 days in group II. In group I although 10 patients showed
      complete healing without any early or late morbidity; two patients suffered from
      severe vulval pain, edema and echymosis, and then developed a total cyst
      necrosis. Healing in these patients completed with mild scar formation. Only one
      recurrence was documented during 24 months follow-up period. All patients in
      group II complained labial pain, four of them suffered from severe labial pain,
      edema, and echymosis. Healing in these patients was completed with moderate scar
      formation. Follow-up of 24 months revealed no recurrence in this group.
      CONCLUSION: Alcohol sclerotherapy of Bartholin's cyst or abscess is as effective
      as silver nitrate application and is associated with less complication. It may be
      ideal, safe and attractive treatment modality for this gynecological disease.

PMID- 14687750
TI  - Laparoscopy and methylene blue intrauterine injection immediately after
      undiagnosed conception: effect on pregnancy and neonatal outcome.
AB  - A 39-year-old woman with infertility and chronic pelvic pain underwent a
      diagnostic laparoscopy with dye-test performed approximately 7 days after
      conception. No effects were reported on pregnancy and neonatal outcome.

PMID- 14687751
TI  - Ovarian ectopic pregnancy after intracytoplasmic sperm injection.
AB  - A ruptured primary ovarian pregnancy occurred following ovulation induction,
      intracytoplasmic sperm injection (ICSI) and embryo transfer (ET). The exact
      mechanism of ovarian pregnancy after intracytoplasmic sperm injection is unclear,
      but, it is possible that there may be an association between blastocyst transfer
      and ovarian pregnancy in infertile patients who underwent ICSI, prolonged in
      vitro culture and fifth day embryo transfer at blastocyst stage.

PMID- 14687752
TI  - Spontaneous ovarian hyperstimulation syndrome caused by hypothyroidism in an
      adult.
AB  - A 22-year-old patient presented with abdominal pain and massive ovarian
      enlargement secondary to severe long standing hypothyroidism, mimicking an
      ovarian cancer. Treatment with L-thyroxin caused marked regression of the tumor.

PMID- 14687753
TI  - First trimester diagnosis of dicephalus conjoined twins.
AB  - Dicephalus twinning is an extremely rare type of conjoined twins. Early prenatal
      diagnosis of this condition is important to provide an opportunity for pregnancy
      termination. We present such a case, which was diagnosed by ultrasound
      examination at 12 weeks of gestation. The ultrasonographic criteria are discussed
      together with implications for management.

PMID- 14687754
TI  - Aggressive angiomyxoma of the vulva and vagina. A common problem: misdiagnosis.
AB  - Aggressive angiomyxoma (AA) is a rare myofibroblastic tumor, usually affecting
      young women. Two patients, one with a vaginal and the other with a vulvar mass
      underwent surgical intervention with different preoperative diagnoses; the former
      as vaginal cyst and the latter as vulvar hernia. Unfortunately, the pathological
      evaluation of the specimens revealed aggressive angiomyxoma. Misdiagnosis of this
      tumor is a common problem.

PMID- 14687755
TI  - Postmenopausal bleeding due to chronic DIC.
AB  - 'Bleeding disorders' are listed as a cause of postmenopausal bleeding even though
      there appear to be no reported cases. We present a case of postmenopausal
      bleeding, because of chronic DIC, which resulted from aortic aneurysm and was
      managed with replacement blood products and tranexamic acid.

PMID- 14687757
TI  - Application of high-throughput Fourier-transform infrared spectroscopy in
      toxicology studies: contribution to a study on the development of an animal model
      for idiosyncratic toxicity.
AB  - An evaluation of high-throughput Fourier-transform infrared spectroscopy (FT-IR)
      as a technology that could support a "metabonomics" component in toxicological
      studies of drug candidates is presented. The hypothesis tested in this study was
      that FT-IR had sufficient resolving power to discriminate between urine collected
      from control rat populations and rats subjected to treatment with a potent
      inflammatory agent, bacterial lipopolysaccharide (LPS). It was also hypothesized
      that co-administration of LPS with ranitidine, a drug associated with reports of
      idiosyncratic susceptibility, would induce hepatotoxicity in rats and that this
      could be detected non-invasively by an FT-IR-based metabonomics approach. The co
      administration of LPS with "idiosyncratic" drugs represents an attempt to develop
      a predictive model of idiosyncratic toxicity and FT-IR is used herein to support
      characterization of this model. FT-IR spectra are high dimensional and the use of
      genetic programming to identify spectral sub-regions that most contribute to
      discrimination is demonstrated. FT-IR is rapid, reagentless, highly reproducible
      and inexpensive. Results from this pilot study indicate it could be extended to
      routine applications in toxicology and to supporting characterization of a new
      animal model for idiosyncratic susceptibility.

PMID- 14687758
TI  - Phthalate ester-induced gubernacular lesions are associated with reduced insl3
      gene expression in the fetal rat testis.
AB  - Targeted inactivation of the insulin-like hormone 3 (insl3) gene in male mice
      results in altered gubernacular development, disrupted testis decent, and
      cryptorchidism. Cryptorchidism is a fairly common human malformation, being
      displayed in about three males per 100 at birth, but only a small percentage can
      be linked directly to genetic defects. The phthalate esters (PEs) are high
      production volume, ubiquitous environmental chemicals, some of which when
      administered during sexual differentiation, induce male rat reproductive tract
      malformations including gubernacular agenesis. We hypothesized that phthalate
      induced gubernacular lesions likely result from an inhibition of insl3 gene
      expression. Three phthalates, di-n-ethylhexyl phthalate (DEHP), dibutyl phthalate
      (DBP) and benzyl butyl phthalate (BBP) were administered orally to the dam on
      gestation day 14 through 18 (GD14-18) and the fetal testes examined on GD18 for
      effects on steroid hormone production and insl3 gene expression. Compared to
      chemicals like vinclozolin, linuron, and prochloraz that act as AR antagonists
      and/or inhibit fetal Leydig cell testosterone production, only the three
      phthalates significantly reduced both ex vivo testosterone production and insl3
      gene expression when quantified by real-time rtPCR. These results provide the
      first demonstration of PE-induced alteration of insl3 mRNA in the fetal male rat
      testis.

PMID- 14687759
TI  - Zinc- or cadmium-pre-induced metallothionein protects human central nervous
      system cells and astrocytes from radiation-induced apoptosis.
AB  - We have shown the protection of human central nervous system (CNS) cultures by
      zinc (Zn) or cadmium (Cd)-pre-induced metallothionein (MT) synthesis from
      radiation-induced cytotoxicity (lactate dehydrogenase (LDH) release and neuronal
      dendritic injury). The present study is to further define the types of cell death
      induced by different dose levels of radiation and investigate the effect of MT
      induction (by Zn or Cd) on radiation-induced apoptosis in primary human CNS and
      astrocyte cultures. Apoptosis was detected by fragmented DNA electrophoresis,
      TUNEL technique, and propidium iodide staining. Expression of MT protein was
      examined by immunofluorescent staining. Results showed that exposure of primary
      human CNS cultures to 15 and 30 Gy gamma-radiation predominantly induced
      apoptotic cell death, while exposure to 60 Gy gamma-radiation predominantly
      induced necrotic cell death. Normal primary human CNS cultures showed weak MT
      staining, while primary human CNS cultures exposed to Zn or Cd showed intense MT
      staining. The induced apoptotic cell death by exposure to 30 Gy gamma-radiation
      increased to a maximum level at 12 and 24 h, and was reduced significantly by Zn
      or Cd pre-induced MT. Using primary human astrocytes, the induction of MT protein
      by Zn or Cd was further confirmed. The enhanced MT expression also afforded a
      significant protection from 30 Gy gamma-ray-induced apoptosis in the primary
      human astrocytes. These results suggest that MT protected human CNS cells from
      apoptosis following ionizing radiation, probably through its antioxidant
      property.

PMID- 14687760
TI  - Additive pro-oxidative effects of methylmercury and ebselen in liver from
      suckling rat pups.
AB  - Oxidative stress has been pointed as an important molecular mechanism for liver
      injury in methylmercury (MeHg) poisoning. Ebselen, a seleno-organic compound that
      possesses anti-oxidant properties, is a useful therapeutic agent used in clinical
      situations involving oxidative stress. Here, we examined the possible in vivo
      protective effect of ebselen against the pro-oxidative effects of MeHg in liver
      from suckling rat pups. The effects of MeHg exposure (subcutaneous injections of
      methylmercury chloride: 2 mg/kg) on the hepatic levels of thiobarbituric acid
      reactive substances (TBARS) and non-ptotein thiols (NPSH), and on liver
      glutathione peroxidase (GSHPx) activity, as well as the possible antagonist
      effect of ebselen (10 mg/kg; subcutaneously) against MeHg effects, were evaluated
      during the post-natal period. In addition, the possible in vitro interaction
      between ebselen, glutathione (GSH) and MeHg was investigated by light/UV
      spectroscopy, with particular attention to the formation of complexes involving
      ebselen selenol intermediate and MeHg. After in vivo exposure, MeHg and ebselen
      alone increased hepatic TBARS levels. Moreover, simultaneous treatment with both
      compounds caused a higher increase in hepatic TBARS levels when compared to the
      treatments with individual compounds. Liver NPSH decreased after treatments with
      MeHg and ebselen alone. A significant negative correlation between hepatic TBARS
      and NPSH was observed. MeHg alone decreased liver GSHPx activity and ebselen,
      which did not affect this variable per se, reverted this inhibitory effect of
      MeHg. Light/UV spectroscopy showed that ebselen and GSH form a chemical
      intermediate that regenerates ebselen after MeHg addition. The presented results
      show that ebselen abolished the MeHg-induced inhibition on liver GSHPx activity,
      but did not prevent the oxidative effects of MeHg on liver lipids and NPSH. MeHg
      affects the in vitro interaction between ebselen and GSH and this phenomenon
      seems to be responsible for its inhibitory effect toward thiol-peroxidase
      activity. Additionally, ebselen presents pro-oxidative effects on rat liver,
      pointing to thiol depletion as a molecular mechanism related to ebselen-induced
      hepatotoxicity.

PMID- 14687761
TI  - A piglet model for studies of gastrointestinal uptake of cadmium in neonates.
AB  - Newborns are believed to have a higher gastrointestinal uptake of inorganic
      cadmium (Cd) than adults. However, relevant models for investigations of
      absorption of dietary Cd in neonates are lacking. In the present study, piglets
      were exposed to 2 or 20 microg Cd/kg body weight (b wt) per day by repeated oral
      administrations of CdCl2 dissolved in deionized water or infant follow-up formula
      from days 0 to 10. Elevated and dose-dependent Cd retention in blood and tissues
      resulted from this low-dose Cd exposure, as determined at day 11. Follow-up
      formula reduced Cd uptake in comparison to deionized water. However, Cd
      distribution to the kidneys was higher when Cd was given in formula than in
      water. Metallothionein (MT) levels in liver, kidney and duodenum were six, three
      and two times higher, respectively compared to an un-exposed control. Differences
      in bioavailability and distribution of low-dose Cd given in various diets to
      newborns could be detected by the proposed piglet model.

PMID- 14687762
TI  - Myeloperoxidase-catalyzed oxidation of chloroacetonitrile to cyanide.
AB  - Chloroacetonitrile (CAN) is a disinfection by-product of chlorination of drinking
      water. Epidemiological studies indicate that it might present a potential hazard
      to human health. The present work provides an evidence for CAN activation to
      cyanide (CN-) by myeloperoxidase (MPO)/hydrogen peroxide (H2O2)/chloride (Cl-)
      system in vitro. Optimum conditions for the oxidation of CAN to CN- were
      characterized with respect to pH, temperature and time of incubation as well as
      CAN, MPO, H2O2 and KCl concentrations in incubation mixtures. The kinetic
      parameters governing the reaction; maximum velocity (Vmax) and Michaelis-Menten
      constant (Km) were assessed. Oxidation of CAN to CN- by NaOCl alone was shown.
      Addition of the MPO inhibitors; sodium azide (NaN3), 4-amino benzoic acid
      hydrazine (ABAH) or indomethacin to the reaction mixtures resulted in a
      significant decrease in the rate of CAN oxidation. Inclusion of the antioxidant
      enzyme catalase (CAT) in the incubation mixtures resulted in a significant
      decrease in the rate of CAN oxidation and CN- formation. Addition of the
      sulfhydryl compounds; glutathione (GSH), N-acetyl-L-cysteine (NAC), L-cysteine or
      D-penicillamine significantly enhanced the rate of CN- release. In conclusion,
      MPO/H2O2/Cl- system has the ability of oxidizing CAN to CN-. The present results
      represent a novel pathway for CAN activation and might be important in explaining
      CAN-induced toxicity.

PMID- 14687763
TI  - Suppressive effects on delayed type hypersensitivity by fasting and dietary
      restriction in ICR mice.
AB  - Dietary restriction improves declining physiologic functions, prevents or lessens
      the severity of neoplasms and autoimmune diseases, and attenuates various
      inflammatory reactions. In the present study, we compared the effect on allergic
      dermatitis from repeated short-term fasting (every 3 days), and from moderate
      dietary restriction receiving 60% of the amount of food consumed by an ad libitum
      feeding group. In addition, we attempted to verify the involvement of
      corticosteroids and oxidative stress during nutritional deprivation. The overall
      food intake in mice undergoing moderate dietary restriction was less than that in
      mice undergoing repeated fasting. Nonetheless, moderate dietary restriction and
      repeated fasting showed similar suppressive effects on dermatitis. Furthermore,
      both the restricted-diet and fasted mice showed less oxidative stress than the
      mice fed ad libitum. In RU486 (a glucocorticoid receptor antagonist)-injected
      mice, no suppressive effect of fasting on dermatitis was seen. In conclusion,
      repeated fasting and moderate dietary restriction suppressed dermatitis in
      similar ways. Hypercorticism and reduced oxidative stress is associated with the
      suppression of dermatitis.

PMID- 14687764
TI  - 2,5-Hexanedione inhibits rat brain acetylcholinesterase activity in vitro.
AB  - A number of C(4)-C9 aliphatic ketones, including 2,5-hexanedione (2,5-HD), are
      acetylcholinesterase (AChE; EC 3.1.1.7) inhibitors. In the previous work, we
      demonstrated that antinociception induced by 2,5-HD was partially reversed by
      atropine. Since cholinergic system seems to be affected by hexacarbon compounds,
      in the present study we examined the effect of 2,5-HD on AChE activity of rat
      brain in vitro. The results demonstrated that both Km and Vmax were altered by
      2,5-HD. At 5 mM 2,5-HD, there were no significant changes in Km or Vmax
      parameters, but at concentrations higher than 10 mM an increase in Km and a
      decrease in Vmax was observed. The Ki plot was linear and the curves intersect on
      the left of the 1/V versus [I] plot. These data characterize an inhibition of the
      mixed type. Although the 2,5-HD concentration that inhibited AChE activity is
      high compared to that attainable in occupationally exposed workers, these data
      are useful in understanding the neurotoxicity of this compound. Furthermore, the
      effect of 2,5-HD on AChE activity must not be a consequence of its effects as an
      organic solvent on protein structure, because total inhibition induced by 2,5-HD
      was partially reversed by increasing substrate concentration.

PMID- 14687765
TI  - Erythrocytotoxicity of tiazofurin in vivo and in vitro detected by scanning probe
      microscopy.
AB  - Tiazofurin (TZF) is a cytostatic drug that leads to depletion of the GTP pool in
      tumor and normal cells via its active metabolite tiazofurin-adenine dinucleotide
      (TAD). TAD was detected in different cell lines, but not in erythrocytes, so the
      mechanism of erythrocytotoxicity of TZF remains unclear. The purpose of this
      study was to evaluate in vitro and in vivo action of tiazofurin on rat
      erythrocytes (RBC). After two decades of clinical trials the question of
      erythrocytotoxicity of TZF had remained unexplained making this study justified.
      Since we have previously demonstrated early erythrocytotoxic effects in male
      Wistar rats, we extend this finding on isolated RBC. Isolated erythrocytes from
      untreated animals were treated in buffered solution or plasma containing TZF. In
      addition, groups of 10 rats were treated with 200 and 1000 mg/kg of TZF and
      hematologic parameters were analyzed by flowcytometry and by the analysis of the
      peripheral blood smears. Early signs of hemolysis or aberrant structures were
      monitored by scanning probe microscopy (SPM). We suggest that correlation exists
      between early erythrocytotoxicity and irregularities in erythrocyte morphology
      and membrane integrity. We also found that TZF affects responsiveness to
      oxidative stress. This is in concordance with flowcytometric findings describing
      anisocytosis and anisochromosis of RBC.

PMID- 14687766
TI  - Serum alcohol concentrations in trauma patients determined by immunoassay versus
      gas chromatography.
AB  - There has been an extensive discussion in the forensic toxicology community
      regarding the effect of trauma on the enzymatic method for ethanol analysis.
      There is a paucity of information in the literature that addresses this question.
      This study was designed to compare the Dade Behring Dimension enzymatic method
      with the reliable gas chromatographic method. The blood samples collected at the
      same time from trauma patients were analyzed by both methods. The result of the
      study shows no significant quantitative difference between the enzymatic and gas
      liquid chromatographic (GLC) methods. Also, the enzymatic method did not show any
      false positive ethanol in cases where the GLC method showed a negative finding.

PMID- 14687767
TI  - A general approach to Bayesian networks for the interpretation of evidence.
AB  - Bayesian networks (BNs) are mathematically and statistically rigorous techniques
      for handling uncertainty. The field of forensic science has recently attributed
      increased attention to the many advantages of this graphical method for assisting
      the evaluation of scientific evidence. However, the majority of contributions
      that relate to this topic restrict themselves to the presentation of already
      "constructed" BNs, and often, only a few explanations are given as to how one
      obtains a specific BN structure for a given problem. Based on several examples,
      the present paper will therefore attempt to explain in more detail some guiding
      considerations that might be helpful for the elicitation of appropriate
      structures for BNs.

PMID- 14687768
TI  - Alleged lethal sorcery in East Timor.
AB  - A wide range of cultural and social perspectives exists on the concept of sudden
      and unexpected death. In countries, without a formal system of death
      investigation, sudden death is shrouded in mysticism often based on traditional
      belief systems. This cultural perspective on sudden death is often at variance
      with medical and forensic concepts and may include explanations such as sorcery,
      magic, and voodoo. In this case report, the postmortem findings in an alleged
      victim of lethal 'black magic', known as ema halo by the indigenous people of
      East Timor, is described. The alleged victim died suddenly in front of witnesses.
      At autopsy, marked dilation of a bicuspid aortic valve with annuloaortic ectasia
      and a sinus of Valsalva aneurysm was found after exhumation of the body. The
      findings mitigated the local belief in witchcraft and established a natural
      manner of death.

PMID- 14687769
TI  - Prevalence of rhabdomyolysis in drug deaths.
AB  - Rhabdomyolysis has repeatedly been reported as a possible consequence of illicit
      drug consumption especially in clinical literature. In order to investigate the
      prevalence of rhabdomyolysis in cases of drug deaths, immunohistochemical
      staining of kidney sections with a myoglobin antibody was performed at 103
      consecutive fatal drug poisonings. The control group consisted of 107 unselected
      forensic autopsies. With regard to the presence of intratubular myoglobin, 33% of
      the study group were categorized as "strongly positive", 17.5% as "slightly
      positive" and 49.5% as "negative". No single substance showed a particularly high
      incidence of rhabdomyolysis nor were there correlations to special combinations
      of substances. In the control group a "strongly positive" result after myoglobin
      staining was observed in only 10.3% of 107 cases, a "slightly positive" result in
      13.1% and a "negative" result in 76.6%. The findings suggest that rhabdomyolysis
      is a frequent consequence of illicit drug consumption and that it is not promoted
      by a single factor, but by a combination of several factors.

PMID- 14687770
TI  - Popliteal artery bullet embolism in a case of homicide: a case report and review
      of the tangible literature.
AB  - Bullet embolism is a well known but a relatively rare phenomenon in common
      medicolegal autopsy practice. We present a homicide case of a bullet embolism to
      the left popliteal artery with interesting trajectory of projectile through the
      chest wall and right heart ventricle into the aortic lumen. Since in our
      presented case obvious homicidal manner of death was in question, discovery of
      bullet was an obligatory part of investigation in order to positively identify
      the responsible firearm. Detection of the missile transported through the
      circulation requires very thorough autopsy examination, especially if X-ray
      equipment is not available. As in all other cases in which initial bullet
      trajectory is changed in the body, the very important part of the medicolegal
      autopsy in cases accompanied with missile embolism, is to determine direction of
      the first part of the bullet's trajectory, because this indicates the position of
      the axis of the weapon barrel in the moment of firing (if there was no external
      ricochet), taking into consideration the posture of the victim and the location
      of the shooting person in the same moment. A review of the tangible literature is
      given.

PMID- 14687771
TI  - Planned complex suicide. Report of two autopsy cases of suicidal shot injury and
      subsequent self-immolation.
AB  - Two cases of planned complex suicide are presented. In both cases, the suicidal
      persons shot themselves after making sure that in the sequel their bodies would
      be burnt. In the first case, a 65-year-old man had shot himself in the mouth and
      consequently fell into a fire he had lighted before. In the second case, a 43
      year-old man set fire to his flat and shot himself directly afterwards. On the
      basis of the reported cases, a short literature review on planned complex
      suicides is given.

PMID- 14687772
TI  - Non-traumatic postmortem computed tomographic (PMCT) findings of the lung.
AB  - PURPOSE: We attempted to obtain postmortem computed tomographic (PMCT) images of
      the lung in cases of non-traumatic death and describe the results to distinguish
      usual postmortem findings from those of specific thoracic causes of death.
      MATERIALS AND METHODS: Our subjects were a total of 150 consecutive non-traumatic
      cases with cardiopulmonary arrest on arrival who were examined by CT within 2h
      after certification of death between January 1993 and December 2001. PMCT images
      of the lung and the frequency of imaging findings (dependent density, ground
      glass attenuation (GGA), consolidation, pleural effusion, and endotracheal (or
      endobronchial) air defect) were retrospectively reviewed. Autopsy had been
      conducted in 16 of the cases. RESULTS: The causes of death and frequency
      percentages of dependent density, GGA, consolidation, pleural effusion, and
      endotracheal (or endobronchial) air defect were: 91 cases of acute heart failure
      (AHF) (69, 66, 24, 11, 14%), 23 cases of aortic dissection (57, 39, 4, 52, 0%),
      11 cases of pneumonia (18, 82, 100, 45, 27%), 23 other specified cases (52, 30,
      13, 17, 9%), and two unspecified cases (0, 0, 0, 50, 0%), [total respective
      frequency percentages were (60, 57, 25, 21, 12%)]. Autopsy confirmed that GGA on
      PMCT in AHF cases corresponded to pulmonary edema. CONCLUSION: When PMCT of the
      lung shows no other shadows than dependent density, further analysis is necessary
      to detect the cause of death.

PMID- 14687773
TI  - Application of cytochrome b DNA sequences for the authentication of endangered
      snake species.
AB  - In order to enforce the conservation program and curbing the illegal trading and
      consumption of endangered snake species, the value of cytochrome b sequence in
      the authentication of snake species was evaluated. As an illustration, DNA was
      extracted, selected cytochrome b DNA sequences amplified and sequenced from six
      snakes commonly consumed in Hong Kong. Cataloging with sequences available in
      public, a cytochrome b database containing 90 species of snakes was constructed.
      In this database, sequence homology between snakes ranged from 70.68 to 95.11%.
      On the other hand, intraspecific variation of three tested snakes was 0-0.98%.
      Using the database, we were able to determine the identity of six meat samples
      confiscated by the Agriculture, Fisheries and Conservation Department, HKSAR.

PMID- 14687774
TI  - Serum tryptase levels in sudden infant death syndrome in forensic autopsy cases.
AB  - An elevated serum tryptase concentration is considered to be a specific marker
      for systemic mast-cell activation, a central feature of anaphylaxis, which has
      been observed in some cases of sudden infant death syndrome (SIDS). However, it
      is still unclear whether anaphylaxis is involved in the etiology for SIDS. In the
      present study, we measured serum tryptase levels in 21 infants with SIDS, and 14
      control infants from forensic autopsy cases by Uni-CAP TRYPTASE Fluoroenzyme
      immunoassay system, which detects both alpha- and beta-tryptase. The assay did
      not show any significant elevation of tryptase levels in the SIDS group compared
      with controls. Additionally, increased concentrations of tryptase were not
      observed in any SIDS case. Our results indicated that anaphylaxis does not seem
      to be involved in the etiology of SIDS.

PMID- 14687775
TI  - Demographic, pathologic, and toxicological profiles of 127 decedents testing
      positive for ephedrine alkaloids.
AB  - The relative toxicity of ephedra-containing dietary supplements is disputed. In
      order to ascertain the magnitude of the problem, we reviewed all autopsies in our
      Medical Examiner's jurisdiction, from 1994 to 2001, where ephedrine or any its
      isomers (E+) were detected. Toxicology testing results were tabulated and
      anatomic findings in E+ cases were compared to those in a control group of drug
      free trauma victims. Of 127 E+ cases identified, 33 were due to trauma. Decedents
      were mostly male (80.3%) and mostly Caucasian (59%). Blood ephedrine
      concentrations were <0.49 mg/l in 50% of the cases, range 0.07-11.73 mg/l in
      trauma victims, and 0.02-12.35 mg/l in non-trauma cases. Norephedrine (NE) was
      present in the blood of 22.8% (mean of 1.81 mg/l, S.D.=3.14 mg/l) and in the
      urine of 36.2% (mean of 15.6 mg/l, S.D.=21.50mg/l). Pseudoephedrine (PE) was
      present in the blood of 6.3% (8/127). More than 88% (113/127) of the decedents
      also tested positive for other drugs, the most common being cocaine (or its
      metabolites) and morphine. The most frequent pathologic diagnoses were hepatic
      steatosis (27/127) and nephrosclerosis (22/127). Left ventricular hypertrophy was
      common, and coronary artery disease (CAD) detected in nearly one third of the
      cases. The most common findings in E+ deaths are those generally associated with
      chronic stimulant abuse, and abuse of other drugs was common in those with CAD.
      There were no cases of heat stroke or rhabdomyolysis. In most cases, norephedrine
      was not detected, suggesting it plays no role in ephedrine toxicity.

PMID- 14687776
TI  - Caffeine fatalities--four case reports.
AB  - Four cases of fatal intoxications with caffeine are described. Caffeine is widely
      available in beverages and in different OTC-products, in many of them in
      combinations with other drugs like ephedrine. Caffeine is not as harmless as one
      might believe. An overdose of caffeine alone, intentional or not, might be
      deadly. It seems to be warranted to include caffeine in the drug-screening of
      forensic autopsy cases. It is not motivated from a medical point of view to sell
      pure caffeine over the counter.

PMID- 14687777
TI  - Temperature-dependent development of Ophyra aenescens (Wiedemann, 1830) and
      Ophyra capensis (Wiedemann, 1818) (Diptera, Muscidae).
AB  - The influence of rearing temperature on the development rates of two "dump flies"
      Ophyra aenescens (Wiedemann, 1830) and Ophyra capensis (Wiedemann, 1818) is
      analysed. The development times of these species are determined. Flies were
      reared at three constant temperatures (17+/-1, 24+/-1 and 30+/-1 degrees C) with
      a photoperiod of 12:12 and at a relativity moisture of 75-95%. The minimum
      duration for each development stages, from eggs to pupae and from eggs to adult
      emergence of O. aenescens and O. capensis are reported. The development rate
      increases in both species as the rearing temperature rises. A temperature
      dependent development model is calculated for each species. The larval and total
      development of these two species can be estimated if the environmental
      temperature is between 17 and 30 degrees C. Compared to O. aenescens, O. capensis
      has a higher threshold of development and a longer larval development time.

PMID- 14687778
TI  - Nine autosomal STRs genotype profiles in a sample from Cordoba (Argentina).
AB  - Nine STRs loci have been typed in a sample from Cordoba (Argentina).

PMID- 14687779
TI  - 10 Y-STRs haplotypes in Chinese.
AB  - Haplotypes of DYS389I, YS389II, DYS439, DYS438, DYS392, DYS393, DYS19, DYS390,
      DYS391, DYS385 were determined from 136 unrelated Chinese male individuals.

PMID- 14687780
TI  - Genetic data on 19 STR loci in south-east Poland.
AB  - Allele frequencies for the 19 STRs loci, D3S1358, D5S818, D7S820, D8S1179,
      D13S317, D16S539, D18S51, D21S11, CSF1PO, F13A01, F13B, FESFPS, FGA, LPL, Penta
      D, Penta E, TH01, TPOX and VWA were obtained from a sample of 203-1188 unrelated
      individuals living in the area of south-east Poland.

PMID- 14687781
TI  - CNS effects after muti ingestion: what is the cause?

PMID- 14687782
TI  - 'Onco-tourism'-season ticket, anyone?

PMID- 14687783
TI  - Eurocare.

PMID- 14687784
TI  - The role of protein kinase C-alpha (PKC-alpha) in malignancies of the
      gastrointestinal tract.
AB  - Drugs specifically designed to block cellular signalling proteins are currently
      evaluated as a new way to treat gastrointestinal tumours. One such "new targeted
      agent" is aprinocarsen, an antisense oligonucleotide that specifically blocks the
      mRNA of protein kinase C-alpha (PKC-alpha). Blocking PKC-alpha, an important
      cellular signalling molecule associated with tumour growth, is anticipated to
      result in tumour cell arrest and achieve clinical benefits. However, it is not
      known which patients may benefit most from a specific inhibition of PKC-alpha.
      Past experience with other novel targeted agents suggests that expression of the
      target molecule is an important factor for the success of such a specific
      therapy. Therefore, reviewing the specific role of PKC-alpha in various
      gastrointestinal tumours may contribute to focus the clinical development of
      selective or specific PKC-alpha inhibitors, such as aprinocarsen, on those
      patients with a distinctive PKC-alpha expression pattern.

PMID- 14687785
TI  - RNA polymerase III transcription--a battleground for tumour suppressors and
      oncogenes.
AB  - This review provides a summary of the European Association for Cancer Research
      Award Lecture, presented at the ECCO12 meeting in Copenhagen in September 2003.
      It describes what we have learnt about the mechanisms responsible for
      deregulating RNA polymerase III transcription in transformed cells. A network has
      been discovered of unanticipated links to key tumour suppressors and oncogenes.
      Novel functions have been revealed for RB, p53 and c-Myc, that may help explain
      their profound biological effects.

PMID- 14687786
TI  - Invariant p53 immunostaining in primary and recurrent breast cancer.
AB  - In animal models, acquired mutations of the p53 gene that result in increased p53
      protein expression are associated with tumour recurrence following chemotherapy.
      The aim of this study was to test the hypothesis that breast cancer recurrences
      following adjuvant therapy exhibit aberrant p53 expression. We therefore
      evaluated p53 expression in paired primary and recurrent breast tumours: 48% of
      primary and 32% of recurrent tumours had abnormally increased p53 expression. Of
      the paired samples, 84% showed no change in p53 expression between the primary
      tumour and the metastasis. In fact, in no case was low (normal) p53 expression in
      the primary tumour followed by the development of high (aberrant) p53 expression
      in the recurrence. These results show that increased p53 expression is not
      selected for in the malignant cells emerging following adjuvant therapy,
      suggesting that p53 expression is unlikely to play a central role in breast
      cancer recurrences.

PMID- 14687787
TI  - Overexpression of c-erbB-2 is related to a higher expression of vascular
      endothelial growth factor (VEGF) and constitutes an independent prognostic factor
      in primary node-positive breast cancer after adjuvant systemic treatment.
AB  - The aim of this study was to investigate possible associations between the
      expression of c-erbB-2 and the angiogenic factors vascular endothelial growth
      factor (VEGF), basic fibroblast growth factor (bFGF), p53 status, routine breast
      cancer prognostic factors and survival. Expression of c-erbB-2, VEGF, bFGF, and
      p53 protein was determined with an enzyme-linked immunosorbent assay (ELISA) in
      656 patients with primary breast cancer (median follow-up time of 83 months). In
      60 cases, we also used immunohistochemistry (IHC) for c-erbB-2 evaluation, to be
      used as a reference for the ELISA. Overexpression of c-erbB-2 was significantly
      related to a higher expression of VEGF, lower bFGF content, negative steroid
      receptor status, and a high S-phase fraction. In multivariate analysis, c-erbB-2
      was an independent prognostic factor for relapse-free survival (RFS) and overall
      survival (OS) in all patients, and in node-positive patients, irrespective of the
      adjuvant systemic therapy. Combined survival analyses regarding c-erbB-2 and VEGF
      yielded additional prognostic information.

PMID- 14687788
TI  - Cognitive dysfunction and subjective complaints of cancer patients. a cross
      sectional study in a cancer rehabilitation centre.
AB  - Although the neurotoxicity of many anticancer therapies is well documented, the
      impact of cancer treatment on cognitive functioning has been studied less
      frequently. The present study examines deficits in cognitive functioning and
      their correlation with medical data as well as with psychosocial variables. A
      standardised neuropsychological test battery and several questionnaires were
      administered to a random sample of 119 patients. 24% of our patients fulfilled
      our criterion for cognitive impairment. There were no significant associations
      between the results of the neuropsychological testing and the current affective
      status or self-reports of attentional deficits in daily life. Cognitive
      impairment occurs in a clinically relevant percentage of cancer patients and
      cannot be explained exclusively due to depression or anxiety. Since subjective
      and objective cognitive impairment data showed little correlation,
      neuropsychological evaluation should not only be based on subjectively-reported
      complaints, but also on objective measurements.

PMID- 14687789
TI  - HER2 and COX2 expression in human prostate cancer.
AB  - COX2 and HER2 expression are associated with a poor prognosis in prostate cancer
      and HER2 has been linked to COX2 expression in colorectal cancer. The association
      between COX2 and HER2 expression was investigated in 117 patients with prostate
      cancer (89) or Benign prostatic hyperplasia (BPH) (28). Tissue was analysed for
      HER2 amplification by fluorescent in situ hybridisation, and HER2 and COX2
      protein expression by immunohistochemistry (IHC). All tumours analysed expressed
      COX2 at a significantly higher level than BPH tissue (P=0.041). Only low levels
      of HER2 gene amplification (8%, 7/89) and HER2 protein expression (12%, 11/89)
      were observed. HER2 protein expression was rarely observed and did not correlate
      with HER2 amplification or COX2 expression. Although HER2 does not drive COX2
      expression in prostate cancer, this study identified high levels of COX2
      expressed in locally advanced prostate cancer, suggesting COX2 could be a
      potential therapeutic target. COX2 inhibitors are currently being used in
      clinical trials for the treatment of other tumour types.

PMID- 14687790
TI  - HER2/neu gene amplification and protein overexpression in G3 pT2 transitional
      cell carcinoma of the bladder: a role for anti-HER2 therapy?
AB  - HER2/neu is an oncogene encoding a type 1 tyrosine kinase growth factor receptor.
      Polysomy 17, gene amplification and HER2/neu protein overexpression are
      associated with a poor prognosis in transitional cell carcinomas (TCC) of the
      bladder. Due to the application of different laboratory techniques, the exact
      incidence of HER/neu abnormalities remains uncertain in TCC. Standardised
      laboratory techniques are therefore important in the determination of the
      HER2/neu status if an assessment of the potential value of anti-HER2/neu
      treatments in the clinical management of patients with TCC is to be made. In this
      study, 75 TCCs with evidence of detrusor muscle invasion at first clinical
      presentation were included. Gene amplification, polysomy 17 and HER2 copy number
      were assessed using fluorescence in situ hybridisation (FISH), with separate
      probes for chromosome 17 and HER2/neu. Protein overexpression was assessed using
      immunohistochemistry (IHC), with the CB11 antibody and a scoring system
      evaluating only membranous staining as positive. The mean patient age was 69.5
      years (range 42-93 years) and the median survival was 15 months (range 1-156
      months). Polysomy 17 occurred in 97%, increased HER/neu copy number in 92% and
      HER2/neu gene amplification in 7%. Protein overexpression occurred in 57% of
      cases. Polysomy 17 and HER2/neu protein overexpression are common in G3 pT2 TCCs
      of the bladder. However, gene amplification is uncommon. Mechanisms other than
      gene amplification may be responsible for protein overexpression in this tumour
      type. Evidence from breast cancer suggests that only tumours with HER2/neu gene
      amplification respond to the anti-HER2/neu therapy trastuzumab (Herceptin). If
      this were true for bladder cancer, only 4/75 (5%) of G3 pT2 TCCs would be
      suitable for treatment. The role of trastuzumab in these tumours remains untested
      at present.

PMID- 14687791
TI  - Association between preoperative plasma levels of tissue inhibitor of
      metalloproteinases 1 and rectal cancer patient survival. a validation study.
AB  - The level of the tissue inhibitor of metalloproteinases 1 (TIMP-1) has previously
      been demonstrated to predict the survival of early stage colorectal cancer
      patients. The present study was undertaken to further validate plasma TIMP-1 as a
      prognostic marker in rectal cancer. Preoperative plasma from 352 rectal cancer
      patients were analysed using an immunoassay for TIMP-1. The TIMP-1 immunoassay
      demonstrated robustness and good reproducibility with low interassay coefficients
      of variation (CV). The rectal cancer patients had a mean plasma TIMP-1 level of
      184 microg/l (standard deviation (SD): 70 microg/l). There were no significant
      differences in TIMP-1 levels between patients with Dukes' stage A, B or C
      disease, whereas Dukes' stage D patients had significantly increased TIMP-1
      levels (P<0.0001); however, high levels of TIMP-1 were not restricted to those
      with advanced disease. Univariate analysis demonstrated an increasing risk of
      mortality with increasing TIMP-1 levels Hazard Ratio (HR)=2.9; 95% Confidence
      Interval (CI): 1.7-5.0; P<0.0001). Including additional covariates, multivariate
      analysis identified plasma TIMP-1 as an independent prognostic marker (HR=2.2;
      95% CI: 1.2-4.1 (P=0.01). This study showed a highly significant and independent
      association between preoperative plasma TIMP-1 levels and survival in rectal
      cancer patients, thus confirming our previous findings. Furthermore, the TIMP-1
      immunoassay proved to be stable and reproducible in this confirmatory study.

PMID- 14687792
TI  - Long-term outcome for patients with non-metastatic Ewing's sarcoma treated with
      adjuvant and neoadjuvant chemotherapies. 402 patients treated at Rizzoli between
      1972 and 1992.
AB  - We evaluated the long-term results obtained in 402 patients with non-metastatic
      Ewing's sarcoma (ES) of the bone treated in a single institution with adjuvant
      and neoadjuvant chemotherapies between 1972 and 1992. Multivariate analyses
      showed male gender, age older than 14 years, high serum lactate dehydrogenase
      (LDH) level, axial location of the tumour, use of radiotherapy alone as a local
      treatment, and poor histological response to chemotherapy, to be independent,
      adverse prognostic factors for event-free survival (EFS). At a mean follow-up of
      about 18 years (10-30 years), 177 patients (44.0%) remained continuously free of
      disease, 2 died of doxorubicin-induced cardiotoxicity and 8 developed a second
      neoplasm (5 died, and 3 are alive and free of disease). 215 patients relapsed
      with metastases and/or local recurrence: 14 are alive and free of disease, 1 is
      alive with uncontrolled disease, and 200 died. The overall survival (OS) at real
      follow-ups of 5-, 10-, 15- and 20-years was 57.2, 49.3, 44.9 and 38.4%,
      respectively. We conclude that since local or systemic relapses, treatment
      complications and second malignancies are more common after 5 years or more from
      the beginning of treatment; a long-term follow-up is mandatory for patients with
      ES.

PMID- 14687793
TI  - Serum enterolactone levels and the risk of breast cancer in women with palpable
      cysts.
AB  - Low levels of lignans, namely enterolactone, have been reported to be associated
      with an increased risk of breast cancer in the general female population. We
      assessed, retrospectively, the relationship between serum enterolactone
      concentrations and the occurrence of breast cancer in women with palpable cysts.
      The levels of enterolactone in cryopreserved serum aliquots, obtained from 383
      women with palpable cysts at the time of their first cyst aspiration, were
      measured using a time-resolved fluoroimmunoassay (TR-FIA). After a median follow
      up time of 6.5 years (range 0.5-12.75 years), 18 women were found to have
      developed an invasive breast cancer. Median values of serum enterolactone were
      significantly lower in women who subsequently developed breast cancer: 8.5 nM/l
      versus 16.0 nM/l: P=0.04. Odd Ratios (OR) for breast cancer were: 0.36 (P=0.03),
      0.57 (P=0.3) and 0.38 (P=0.25) for 25th (8 nM/l), 50th (16 nM/l) and 75th (24
      nM/l) percentile values, respectively. The receiver operating characteristic
      (ROC) analysis showed a satisfactory accuracy for enterolactone as a breast
      cancer risk indicator (area under the curve (AUC)=0.64: P=0.04). Logistic
      regression analysis confirmed that the enterolactone concentration had a strong
      protective effect on the breast cancer risk. These findings may have important
      clinical implications with regard to interventional diet-focused chemo-preventive
      trials.

PMID- 14687794
TI  - Familial clustering of ovarian and endometrial cancers.
AB  - Data on the association of ovarian cancer with other cancers in families are
      limited, and no data are available on the involvement of specific morphological
      types. The nationwide Swedish Family-Cancer Database on 10.2 million individuals
      and 19175 invasive ovarian cancers was used to calculate standardised incidence
      ratios (SIRs) and 95% confidence intervals (CIs) for familial ovarian cancer in 0
      66-year-old daughters when mothers or sisters were affected. The SIR for
      concordant ovarian cancers was increased. When the mother or sister had breast
      cancer, the SIRs were 1.21 and 1.48, respectively; when they had endometrial
      cancer, the SIRs were 1.45 and 2.53. Multiple myeloma in the mother was
      associated with a risk of ovarian cancer in the daughter. The risk of
      endometrioid ovarian cancer was 3.40 in the daughter when the mother presented
      with endometrial cancer. Our data show a strong familial coupling of ovarian and
      endometrial cancers, which appears to be specific to the endometrioid morphology.

PMID- 14687795
TI  - Going up or coming down? The changing phases of the lung cancer epidemic from
      1967 to 1999 in the 15 European Union countries.
AB  - Lung cancer, the most common cause of cancer death in the European Union (EU),
      continues to have an enormous impact on the health experience of the men and
      women living in the constituent countries. Information on the course of the lung
      cancer epidemic is essential in order to formulate an effective cancer control
      policy. This paper examines recent trends in lung cancer mortality rates in men
      and women in each of the 15 countries, comparing cross-sectional rates of death
      in younger (aged 30-64 years) and older populations (aged 65 years or over), and
      the age, period of death, and birth cohort influences in the younger age group.
      The latter analysis establishes the importance of year of birth, related to
      modifications in the tobacco habit among recently born generations. The stage of
      evolution of the lung cancer epidemic varies markedly by sex and country in terms
      of the direction, magnitude, and phase of development of national trends. In
      males, there is some consistency in the direction of the trends between EU
      countries, declines are apparent in most countries, at least in younger men, with
      rates in older men either reaching a plateau, or also falling. In younger
      persons, a decreasing risk of lung cancer death reflects changes in successive
      birth cohorts, due to modifications in the smoking habit from generation to
      generation, although these developments are in very different phases across
      countries. Portugal is the exception to the male trends; there are increases in
      mortality in both age groups, with little sign of a slowing down by birth cohort.
      In women, there are unambiguous upsurges in rates seen in younger and older women
      in almost all EU countries in recent decades, and little sign that the epidemic
      has or will soon reach a peak. The exceptions are the United Kingdom (UK) and
      Ireland, where lung cancer death rates are now declining in younger women and
      stabilising in older women, reflecting a declining risk in women born since about
      1950. It is too early to say whether the observed plateau or decline in rates in
      women born very recently in several countries is real or random. To ascertain
      whether recent trends in lung cancer mortality will continue, trends in cigarette
      consumption should also be evaluated. Where data are available by country, the
      proportion of adult male smokers has, by and large, fallen steadily in the last
      five decades. In women, recent smoking trends are downwards in Belgium, Denmark,
      Sweden and the Netherlands, although in Austria and Spain, large increases in
      smoking prevalence amongst adults are emerging. Unambiguous public health
      messages must be effectively conveyed to the inhabitants of the EU if the lung
      cancer epidemic is to be controlled. It is imperative that anti-tobacco
      strategies urgently target women living in the EU, in order to halt their rapidly
      increasing risk of lung cancer, and prevent unnecessary, premature deaths among
      future generations of women.

PMID- 14687796
TI  - Inequalities in lung cancer mortality by the educational level in 10 European
      populations.
AB  - Previous studies have shown that due to differences in the progression of the
      smoking epidemic European countries differ in the direction and size of
      socioeconomic variations in smoking prevalence. We studied differences in the
      direction and size of inequalities in lung cancer mortality by the educational
      level of subjects in 10 European populations during the 1990's. We obtained
      longitudinal mortality data by cause of death, age, sex and educational level for
      4 Northern European populations (England/Wales, Norway, Denmark, Finland), 3
      continental European populations (Belgium, Switzerland, Austria), and 3 Southern
      European populations (Barcelona, Madrid, Turin). Age- and sex-specific mortality
      rates by educational level were calculated, as well as the age- and sex-specific
      mortality rate ratios. Patterns of educational inequalities in lung cancer
      mortality suggest that England/Wales, Norway, Denmark, Finland and Belgium are
      the farthest advanced in terms of the progression of the smoking epidemic: these
      populations have consistently higher lung cancer mortality rates among the less
      educated in all age-groups in men, including the oldest men, and in all age
      groups in women up to those aged 60-69 years. Madrid appears to be less advanced,
      with less educated men in the oldest age-group and less educated women in all age
      groups still benefiting from lower lung cancer mortality rates. Switzerland,
      Austria, Turin and Barcelona occupy intermediate positions. The lung cancer
      mortality data suggest that inequalities in smoking contribute substantially to
      the educational differences in total mortality among men in all populations,
      except Madrid. Among women, these contributions are probably substantial in the
      Northern European countries and in Belgium, but only small in Switzerland,
      Austria, Turin and Barcelona, and negative in Madrid. In many European countries,
      policies and interventions that reduce smoking in less educated groups should be
      one of the main priorities to tackle socioeconomic inequalities in mortality. In
      some countries, particularly in Southern Europe, it may not be too late to
      prevent women in less educated groups from taking up the smoking habit, thereby
      avoiding large inequalities in mortality in the future in these countries.

PMID- 14687797
TI  - Genetic analysis of the LKB1/STK11 gene in hepatocellular carcinomas.
AB  - The tumour suppressor gene, LKB1/STK11, has been mapped to chromosome 19p13, a
      region showing frequent allelic loss in various human cancers, including
      hepatocellular carcinoma (HCC). Additionally, LKB1 physically associates with p53
      and regulates p53-dependent apoptotic pathways. To investigate whether genetic
      alterations of LKB1 could be involved in the tumorigenesis of HCC, we analysed
      the genetic alterations of the LKB1 and p53 genes in seven dysplastic nodules and
      80 HCCs. We found one LKB1 missense mutation, CCG-->CTG (Pro-->Leu) at codon 281
      within the kinase domain. We also found allelic loss in six of 27 (22%)
      informative HCC cases and all of them were HBV-positive cases. In addition, we
      detected seven missense, one nonsense and one silent mutations (nine of 80, 11%)
      of p53 in HCCs only. These results suggest that genetic alterations of the LKB1
      or p53 genes may play an important role in tumour development or progression of a
      sub-set of HCCs, and may also provide alternative mechanisms to protect the HCC
      cell from p53-dependent apoptosis.

PMID- 14687798
TI  - Uptake of 5-fluorouracil (5-FU) in peritoneal metastases in relation to the route
      of drug administration and tumour debulking surgery. an autoradiographic study in
      the rat.
AB  - Patients with peritoneal metastases from colorectal cancer have a poor prognosis.
      Aggressive treatment by debulking surgery and intraperitoneal (i.p.) chemotherapy
      has been suggested as an alternative therapy. However, the drug penetrance into
      the tumour in relation to the administration route and surgical reduction of the
      tumour is not well known. We compared locoregional administration with
      intravenous (i.v.) injection. Thirty-four in-bred rats with peritoneal metastases
      were randomly allocated into eight groups and injected with 14C-labelled 5
      fluorouracil (5-FU) either through the i.v. or i.p. route, with or without a
      preceding tumour debulking, and were sacrificed after 2 or 8 h. Tumour
      radioactivity was visualised by autoradiography and quantified by a computer
      based image analysis. After 8 h, 19 debulked and i.p.-injected tumours had a
      higher drug uptake, 63.2+/-28 (mean+/-standard deviation (SD)) kBq/g than 62
      native i.p.-injected tumours (32.8+/-14) or 22 debulked and i.v.-injected tumours
      (18.5+/-18, P=0.002). After 8 h, 9 small tumours (<median 571 pixels) which
      underwent i.p. injection and tumour reduction had a higher drug uptake (77.4+/
      26) than 29 non-debulked and i.p.-injected (35.1+/-17) or eight debulked and i.v.
      injected tumours (23.0+/-16, P=0.004). For larger tumours (>/=median 571 pixels),
      16 debulked and i.p.-injected tumours had a higher radioactivity (drug uptake)
      (150.7+/-63) at 2 h than 49 i.p.-injected native tumours (48.5+/-59) or 11
      reduced and i.v.-injected tumours (19.9+/-13, P=0.03). At 8 h, 10 debulked and
      i.p.-injected tumours had a higher drug uptake (50.3+/-24) than 33 native and
      i.p.-injected (30.8+/-10) or 14 debulked and i.v.-injected tumours (16.0+/-19,
      P=0.001). These results indicate that a debulking procedure and locoregional
      treatment of peritoneal metastases is associated with an increased level of 5-FU
      in the tumours.

PMID- 14687799
TI  - Design of a multivalent galactoside ligand for selective targeting of HPMA
      copolymer-doxorubicin conjugates to human colon cancer cells.
AB  - N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymers have been shown to be
      efficient carriers for anticancer drugs because of their versatile chemistry and
      good biocompatibility. As demonstrated with hepatocytes, targeting efficacy of
      anticancer drugs could be further improved when the drug (doxorubicin) was
      conjugated to HPMA copolymers with biorecognisable groups, such as simple
      carbohydrates. The present study was devised to learn whether the cluster
      (multivalent) construction of carbohydrate residues could improve the targeting
      capability of HPMA copolymer-doxorubicin (DOX) conjugates towards human colon
      adenocarcinoma cells. DOX was linked via a lysosomally degradable tetrapeptide
      sequence to HPMA copolymers bearing galactosamine (GalN), lactose (Lac), or
      multivalent galactose residues (TriGal) to produce targetable polymeric drug
      carriers. The effect of the type of sugar moiety and its three-dimensional
      cluster arrangement on biorecognition by three human colon-adenocarcinoma cell
      lines was studied. The role of galectin-3 in the biorecognition of HPMA copolymer
      conjugates was explored. Biorecognition of the targetable (glycoside-bearing)
      conjugates decreased their IC(50) doses in comparison to the non-targetable (non
      glycosylated) conjugates. The biorecognition of the TriGal-containing HPMA
      copolymer-doxorubicin conjugate by the cells was superior with concomitant
      decrease of its IC(50) doses. It is suggested that the increased cytotoxicity of
      the glycosylated HPMA-copolymer-DOX conjugates toward human colon-adenocarcinoma
      cells was caused by their biorecognition and effective internalisation via
      receptor-mediated endocytosis. All three human colon adenocarcinoma cell lines
      tested, Colo-205, SW-480 and SW-620, expressed the galectin-3 protein and the
      galectin-3-specific RNA. However, contrary to expectation, Colo-205 cells did not
      express a detectable amount of galectin-3 on the cell surface. This suggests that
      the binding of the glycoside-bearing HPMA copolymer-DOX conjugates to the cells
      was mediated not only by galectin-3. We conclude that targeting of the anticancer
      agent, doxorubicin, using HPMA copolymer conjugates bearing multivalent
      galactoside residues can improve their cytotoxicity.

PMID- 14687800
TI  - Model for paraaortic lymph node metastasis produced by orthotopic implantation of
      ovarian carcinoma cells in athymic nude mice.
AB  - Lymph node metastasis through the lymphatic vessels is a critical step in
      determining the outcome of ovarian cancer patients, and prognosis should be
      improved by preventing lymph node metastasis. However, experimental models for
      lymph node metastasis of ovarian carcinoma are not available. We developed an
      orthotopic transplantation model to study this process in nude mice using the
      human ovarian carcinoma cell lines, KF and MH. Highly metastatic sublines (KF-LN3
      and MH-LN3) were selected in vivo in nude mice by repeated orthotopic
      transplantation, lymph node metastasis formation and culturing the tumour cells
      in vitro. Because this model seems to correspond to the advanced clinical stage
      of ovarian carcinomas, it should be useful in understanding the molecular biology
      of ovarian carcinomas and in the development of therapeutic modalities against
      lymph node metastasis.

PMID- 14687801
TI  - Primary screening with colonoscopy for colorectal cancer: a targeted algorithm?

PMID- 14687802
TI  - Commentary on "Long-term outcome of percutaneous transhepatic cholangioscopic
      lithotomy for hepatolithiasis".

PMID- 14687803
TI  - Abdominal and digestive system associations of familial Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is a hereditary episodic febrile syndrome that
      is expressed by acute spells of fever, painful manifestations in the abdomen,
      chest and joints, and slow development of nephropathic amyloidosis. Despite the
      recent cloning of the FMF gene (MEFV) and the identification of about 40 disease
      related mutations, the diagnosis is still clinically dependent, and the
      pathogenesis and most of the clinical heterogeneity remain to be explained.
      Because episodic abdominal pain affects 95% of FMF patients, most of them are
      seen by gastroenterologists and undergo complete or partial abdominal imaging
      before the diagnosis is made. Focusing on recent advances in FMF, this article
      reviews both common and infrequent manifestations that a gastroenterologist may
      encounter during workups of FMF patients. These include episodic abdominal pain,
      paralytic or mechanical ileus, constipation, diarrhea, ascites, malabsorption,
      bowel infarction, and bleeding, arising directly from FMF or secondary to FMF
      common associations such as amyloidosis, vasculitides, inflammatory bowel
      disease, irritable bowel syndrome, or colchicine side effects. This article will
      help the gastroenterologist to cope with most clinical situations related to the
      abdominal and alimentary tract in patients with FMF.

PMID- 14687804
TI  - Does gallbladder ejection fraction predict outcome after cholecystectomy for
      suspected chronic acalculous gallbladder dysfunction? A systematic review.
AB  - The clinical utility of cholecystokinin-cholescintigraphy with calculation of a
      gallbladder ejection fraction (GBEF) in patients with suspected chronic
      acalculous gallbladder dysfunction (CAGD) remains controversial. It was our aim
      to critically evaluate the literature on the utility of the GBEF to predict
      outcome of patients with suspected CAGD. We performed an electronic search of the
      MEDLINE database for articles published between 1980 and 2002 and a manual search
      of references from bibliographies of identified articles. Only articles in
      English that concerned adults were screened. Data extracted included both
      qualitative and quantitative data reported on the study groups,
      cholescintigraphic technique, interventions, treatment outcomes, and trial
      methodologic characteristics. Twenty-three publications met the inclusion
      criteria. All were considered of poor methodologic quality. All but three studies
      were retrospective case series, only one was randomized, and none were adequately
      blinded, used adequate controls, or enrolled a sufficient number of patients.
      Five studies used a cut-off value for an abnormal GBEF that was different than
      the value used by the others, one study did not provide a cut-off value, and
      several did not report details of the cholescintigraphic technique (namely, the
      rate of cholecystokinin infusion). Studies varied in their outcome measures and
      the criteria for success. The overall assessment of outcome in 19 studies
      concluded that calculation of a GBEF was useful in patients with suspected CAGD.
      The low methodologic quality of the studies precluded a meta-analysis approach to
      the data. Use of a calculated GBEF to diagnose and predict treatment outcome in
      suspected CAGD has not been adequately studied. Although most studies report
      utility of GBEF in predicting symptom outcome after cholecystectomy in patients
      with suspected CAGD, quality evidence is lacking, thereby precluding a definitive
      recommendation regarding its use. More high quality trials are needed.

PMID- 14687805
TI  - Progression or regression of Barrett's esophagus--is it all in the eye of the
      beholder?
AB  - OBJECTIVES: Accurate measurements of Barrett's esophagus length are important in
      clinical follow-up as well as in studies of therapeutic intervention in Barrett's
      esophagus. Our aim was to evaluate both the inter- and intraobserver reliability
      in measuring Barrett's length during two consecutive endoscopies by either the
      same or different experienced endoscopists. The relationship between Barrett's
      mucosa length and the absolute change in Barrett's length measurements on a
      follow-up endoscopy was also evaluated. METHODS: A total of 96 Barrett's patients
      underwent two consecutive endoscopies. The diagnosis of Barrett's esophagus was
      confirmed by the presence of intestinal metaplasia on biopsy. The Barrett's
      esophagus length was carefully measured and recorded during the two endoscopies.
      Procedures were performed by only two experienced endoscopists, who were not
      aware of previous endoscopic measurements. Only patients with long-segment (> or
      =3 cm) Barrett's esophagus were included in this study. RESULTS: The 55 patients
      who had their consecutive endoscopies performed by the same endoscopist had a
      mean 1.6-cm difference between the two measurements as compared to 1.4 cm in the
      41 patients who had their endoscopies performed by different endoscopists (p =
      0.3). The agreement between the two Barrett's length measurements was high in
      both groups, although it was slightly higher for endoscopies performed by the
      same endoscopist (r = 0.79 vs r = 0.67). Linear regression analysis of the
      absolute change in Barrett's length between the two endoscopic measurements and
      Barrett's mucosa length demonstrated a significant relationship (r = 0.28, p =
      0.005). For every 1-cm increase in the mean length of Barrett's mucosa, a 0.15-cm
      increase in the absolute difference between two consecutive endoscopic
      measurements of Barrett's length was observed. CONCLUSIONS: Consecutive
      measurements of Barrett's length performed by different experienced endoscopists
      or by the same experienced endoscopist demonstrated a high degree of agreement. A
      range of variability in Barrett's length measurement was determined (+/-1.4-1.6
      cm). True regression or progression of Barrett's mucosa should be considered only
      if the change is greater than the range of variability. In addition, endoscopists
      should be well aware that the longer the Barrett's mucosa the greater the
      absolute difference in Barrett's length measurement on follow-up endoscopy.

PMID- 14687806
TI  - Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole,
      and rabeprazole: a five-way crossover study.
AB  - OBJECTIVES: Proton pump inhibitors owe their clinical efficacy to their ability
      to suppress gastric acid production. The objective of this study was to evaluate
      and compare intragastric pH following standard doses of esomeprazole,
      lansoprazole, omeprazole, pantoprazole and rabeprazole. METHODS: This randomized,
      open-label, comparative five-way crossover study evaluated the 24-h intragastric
      pH profile of oral esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg,
      pantoprazole 40 mg, and rabeprazole 20 mg once daily in 34 Helicobacter pylori
      negative patients aged 18-60 yr with symptoms of gastroesophageal reflux disease.
      Patients were randomly assigned to one of five treatment sequences and study drug
      was taken on 5 consecutive mornings 30 minutes prior to a standardized breakfast.
      A washout period of at least 10 days separated each treatment phase. RESULTS:
      Thirty-four patients provided evaluable data for all five comparators. The mean
      number of hours of evaluable pH data was > or =23.75 hours. On day 5,
      intragastric pH was maintained above 4.0 for a mean of 14.0 h with esomeprazole,
      12.1 h with rabeprazole, 11.8 h with omeprazole, 11.5 h with lansoprazole, and
      10.1 h with pantoprazole (p < or = 0.001 for differences between esomeprazole and
      all other comparators). Esomeprazole also provided a significantly higher
      percentage of patients with an intragastric pH greater than 4.0 for more than 12
      h relative to the other proton pump inhibitors (p < 0.05). The frequency of
      adverse events was similar between treatment groups. CONCLUSIONS: Esomeprazole at
      the standard dose of 40 mg once daily provided more effective control of gastric
      acid at steady state than standard doses of lansoprazole, omeprazole,
      pantoprazole, and rabeprazole in patients with symptoms of gastroesophageal
      reflux disease.

PMID- 14687807
TI  - An update of the Cochrane systematic review of Helicobacter pylori eradication
      therapy in nonulcer dyspepsia: resolving the discrepancy between systematic
      reviews.
AB  - OBJECTIVES: A Cochrane systematic review on the efficacy of Helicobacter pylori
      (H. pylori) eradication therapy in nonulcer dyspepsia concluded that this
      intervention had a small but statistically significant effect in curing symptoms.
      A systematic review in the Annals of Internal Medicine suggested that there was
      no statistically significant effect of H. pylori eradication therapy on nonulcer
      dyspepsia symptoms. We updated the Cochrane review and explored reasons for these
      discrepant results. METHODS: In our update of the Cochrane review we included
      randomized controlled trials evaluating H. pylori eradication in nonulcer
      dyspepsia published up to September, 2002. A statistician and the lead author of
      two negative randomized controlled trials explored reasons for the differences
      between the Cochrane and Annals systematic reviews according to the review
      methodology, data analyzed, and statistical methods. Sensitivity analyses were
      undertaken to evaluate which differences had an impact on the review conclusions.
      RESULTS: The updated review identified 12 trials evaluating H. pylori eradication
      versus placebo antibiotics in 2903 patients. H. pylori eradication reduced
      nonulcer dyspepsia (nonulcer dyspepsia relative risk = 0.91; 95% CI = 0.86-0.95).
      We identified five differences in methodology between the Cochrane and Annals
      reviews. The Annals review included all dual, triple, and quadruple H. pylori
      eradication therapies searched until December, 1999; did not contact authors for
      further information; included abstracts; and assumed that dropouts were treatment
      failures. The Cochrane review included only those therapies proved to be
      successful in eradicating H. pylori; searched until May, 2000; contacted authors
      for further information; included abstracts only if further information was
      available; and excluded dropouts from the analysis. Not including trials
      published in 2000 reduced the number of trials in the review and the number of
      patients evaluated, changing the conclusions from evidence of benefit to benefit
      not being proved. The method of statistical analysis did not alter conclusions
      when all studies were included. CONCLUSIONS: The results of systematic reviews in
      a rapidly developing field depend on inclusion of all relevant studies. There is
      evidence for a small benefit of eradicating H. pylori in nonulcer dyspepsia, and
      this is confirmed by updating the Cochrane systematic review.

PMID- 14687808
TI  - Incidence of outpatient physician claims for upper gastrointestinal symptoms
      among new users of celecoxib, ibuprofen, and naproxen in an insured population in
      the United States.
AB  - OBJECTIVE: The aim of this study was to compare the risk of outpatient medical
      claims for UGI symptoms among new users of celecoxib versus ibuprofen, and
      naproxen. METHODS: The study was conducted using LifeLink, an insurance claims
      database of approximately 1.8 million employees, dependents, and retirees in the
      United States. Patients newly treated with a prescription of celecoxib,
      ibuprofen, or naproxen between June 1, 1999, and June 30, 2001, were included. A
      patient with an upper GI (UGI) symptom was any individual with an outpatient
      physician claim for dyspepsia (ICD-9 = 536.8), abdominal pain (789.0), or
      nausea/vomiting (787.0). Incidence was determined using person-time analysis.
      Multivariate analyses were conducted using Poisson and Cox regression models.
      RESULTS: The cohort consisted of patients prescribed celecoxib (n = 68,939),
      ibuprofen (n = 71,456), or naproxen (n = 50,014). At baseline, celecoxib users
      were older and more likely to have a history of UGI or cardiovascular conditions.
      The incidence rate of any UGI symptom was 0.46 per 1,000 patient-days for
      celecoxib, 0.70 for ibuprofen, and 0.62 for naproxen. After adjusting for
      confounding factors using Poisson regression, the ibuprofen rate was 48% higher
      than the celecoxib rate (incidence rate ratio (IRR) = 1.48; 95% CI = 1.39-1.58; p
      < 0.001), whereas the naproxen rate was 40% higher (IRR = 1.40; 95% CI = 1.31
      1.49; p < 0.001). The association between drug use and UGI symptoms was confirmed
      by Cox regression analysis; the hazard ratios were 1.21 (95% CI = 1.13-1.29; p <
      0.001) for ibuprofen and 1.15 (95% CI = 1.07-1.23; p < 0.001) for naproxen
      relative to celecoxib. Younger age, female sex, medical history of UGI,
      cardiovascular and renal conditions, and higher baseline average healthcare
      expenditures for the 12-month period preceding the index prescription were also
      significantly associated with an increased incidence of UGI symptoms.
      CONCLUSIONS: Celecoxib use is associated with a significantly decreased risk of
      outpatient physician claims for UGI symptoms compared with commonly used
      prescription nonspecific nonsteroidal anti-inflammatory drugs.

PMID- 14687809
TI  - Intragastric pH during continuous infusion with pantoprazole in patients with
      bleeding peptic ulcer.
AB  - OBJECTIVES: In managing patients with bleeding peptic ulcers, prevention of
      rebleeding is a particular challenge to hemostasis and fibrinolysis, both of
      which involve reactions that are impaired in acidic gastric environment.
      Therefore, such patients are expected to benefit from profound acid suppression.
      The present investigation aimed to establish a safe and, with regard to pH
      elevation, effective treatment that, based on in vitro evidence, should provide
      clinical benefit in this patient population. METHODS: Patients with acute
      bleeding peptic ulcers (Forrest Ia, Ib, IIa) after successful endoscopic
      hemostasis were enrolled in two pilot studies (N = 20 each). They were given an
      intravenous bolus injection of 80 mg of pantoprazole immediately followed by
      continuous infusion of either 6 mg/h or 8 mg/h pantoprazole for 72 h.
      Intragastric pH was measured continuously over 24 h and, if possible, for up to
      48 h. RESULTS: Intragastric pH increased rapidly to values of about 6 with both
      treatments. For the 0-24 h period, the median pH values were 6.1 (68% range 4.5
      7.4) and 6.1 (68% range 5.2-6.7) in patients receiving 6 mg/h and 8 mg/h
      continuous infusion, respectively; the values for the 0-48 h period were 5.9 (4.9
      6.7) and 6.3 (5.5-7.0), respectively. The median percentage time that pH was > or
      =6 during the 0-48 h interval was 47% (68% range 28-89) for the 6 mg/h treatment
      group and 64% (68% range 41-84) for the 8 mg/h treatment group. Both treatment
      regimens with pantoprazole were well tolerated based on electrocardiographic
      measurements, vital signs, clinical laboratory values, and adverse events.
      CONCLUSIONS: Compared with the infusion with 6 mg/h pantoprazole, the continuous
      infusion of 8 mg/h pantoprazole showed a lower interindividual variability of the
      intragastric pH and a greater percentage of time that pH was >/ or =6. Thus, with
      regard to safety and efficacy, an initial 80-mg bolus injection, followed by 8
      mg/h continuous infusion, seems to be the adequate treatment in patients with a
      high risk of rebleeding.

PMID- 14687810
TI  - An impaired accommodation of the proximal stomach to a meal is associated with
      symptoms after distal gastrectomy.
AB  - OBJECTIVE: The aim of this study was to assess gastric emptying and postprandial
      proximal gastric tone variations depending on the presence of postoperative
      symptoms after Billroth II gastrectomy (BII). METHODS: A total of 16 consecutive
      patients were prospectively studied 10 +/- 3 months after distal gastrectomy for
      antral cancer. No evidence of cancer recurrence was detected at the time of the
      study. Ten patients were asymptomatic after surgery, whereas six patients were
      considered as symptomatic because of at least one weekly epigastric pain,
      postprandial fullness, nausea, or vomiting. The fasting fundus volume and tone,
      the onset of a gastric relaxation after a standard 200-kcal liquid meal, and the
      characteristics of this relaxation (delay of occurrence, amplitude) were
      determined with a barostat. Patient results were compared to normal values
      obtained in 12 healthy volunteers. Gastric emptying studies were performed in all
      patients using the C(13) acid octanoic breath test after a 250-kcal meal.
      RESULTS: In the patients, both fasting fundus tone (BII 7.0 +/- 0.5, controls 8.4
      +/- 2.4 mm Hg) and volume (BII 108 +/- 11, controls 119 +/- 29 ml) were not
      different from controls. Fasting fundus tone was lower in asymptomatic patients
      than in symptomatic patients (6.5 +/- 0.4 vs 8.1 +/- 0.5 mm Hg, p < 0.04).
      Gastric relaxation was observed immediately after the meal in all asymptomatic
      patients as well as in controls. In contrast, gastric relaxation occurred in only
      two of six symptomatic patients (p < 0.01); when it occurred it was delayed by
      the meal and was observed only 23 +/- 1 min after food intake. When a relaxation
      occurred, its amplitude was higher than that observed in controls both in
      asymptomatic and symptomatic patients (294 +/- 21 vs 179 +/- 53 ml, p < 0.02).
      CONCLUSIONS: After distal gastrectomy, gastric accommodation is impaired (i.e.,
      absent or delayed) in symptomatic patients. When relaxation exists in these
      patients, its amplitude is higher than in control subjects.

PMID- 14687811
TI  - Use of colonoscopy as a primary screening test for colorectal cancer in average
      risk people.
AB  - OBJECTIVE: The use of colonoscopy as a primary screening test for colorectal
      cancer (CRC) in average risk adults is a subject of controversy. Our primary
      objective was to build a predictive model based on a few simple variables that
      could be used as a guide for identifying average risk adults more suitable for
      examination with colonoscopy as a primary screening test. METHODS: The prevalence
      of advanced adenomas was assessed by primary screening colonoscopy in 2210
      consecutive adults at least 40 yr old, without known risk factors for CRC. Age,
      gender, and clinical and biochemical data were compared among people without
      adenomas, those with non-advanced adenomas, and those with any advanced neoplasm.
      A combined score to assess the risk of advanced adenomas was built with the
      variables selected by multiple logistic regression analysis. RESULTS: Neoplastic
      lesions were found in 617 subjects (27.9%), including 259 with at least one
      neoplasm that was 10 mm or larger, villous, or with moderate-to-severe dysplasia,
      and 11 with invasive cancers. Advanced lesions were more frequent among men,
      older people, and those with a higher body mass index (BMI). These three
      variables were independent predictors of advanced adenomas in multivariate
      analysis. A score combining age, sex, and BMI was developed as a guide for
      identifying individuals more suitable for screening colonoscopy. CONCLUSIONS:
      Age, gender, and BMI can be used to build a simple score to select those average
      risk adults who might be candidates for primary screening colonoscopy.

PMID- 14687812
TI  - Long-term outcome of percutaneous transhepatic cholangioscopic lithotomy for
      hepatolithiasis.
AB  - OBJECTIVES: Percutaneous transhepatic cholangioscopic lithotomy (PTCSL) for the
      treatment of hepatolithiasis is particularly suited for those patients who are
      poor surgical risks or who refuse surgery and those with previous biliary surgery
      or stones distributed in multiple segments. However, hepatolithiasis is
      characterized by high rates of treatment failure and recurrence. We examined the
      long-term results of 245 patients with hepatolithiasis treated by PTCSL. METHODS:
      This was a retrospective study of 245 patients who underwent PTCSL for
      hepatolithiasis; the patients were followed for 1-22 yr to evaluate the immediate
      and long-term results. Sonography was used to search for stone recurrence every
      year or whenever the patients presented symptoms suggestive of cholangitis.
      Cholangiography and/or CT were performed to verify recurrence. RESULTS: PTCSL
      achieved complete clearance of hepatolithiasis in 209 patients (85.3%); the rate
      of incomplete clearance was higher in patients with intrahepatic duct stricture
      (29/118, 24.6% vs 7/127, 5.5%; p = 0.002). The rate of major complications was
      1.6% (4/245) and included liver laceration (n = 2), intra-abdominal abscess (n =
      1), and disruption of the percutaneous transhepatic biliary drainage fistula (n =
      1). The overall recurrence rate of hepatolithiasis and/or cholangitis was 63.2%.
      The absolute rate of stone recurrence was not significantly related to the
      presence of intrahepatic duct stricture (51/89, 56.2% vs 53/120, 44.4%; p =
      0.08), although the median time to recurrence was less in those with stricture
      (11 vs 18 yr; p = 0.007). In the patients without intrahepatic duct stricture,
      the rate of complete stone clearance was not related to the presence of dilation
      (34/38, 89.5% vs 86/89, 96.6%; p = 0.196), but the recurrence rate was higher in
      those with dilation (20/34, 58.8% vs 33/86, 38.4%; p = 0.042). Among the 209
      patients with a successful initial PTCSL, the incidence of recurrent cholangitis
      or cholangiocarcinoma was significantly higher in those with incompletely removed
      recurrent hepatolithiasis than in those without coexisting hepatolithiasis
      (44.3%, 27/61 vs 16.2%, 24/148; p < 0.001 and 6.6%, 4/61 vs 0.7%, 1/148; p =
      0.026). CONCLUSIONS: PTCSL is a relatively safe and effective procedure for
      treating hepatolithiasis. Long-term follow-up is required because the overall
      recurrence rate of hepatolithiasis and/or cholangitis is high. The rate of
      complete stone clearance and the median time to stone recurrence are less in the
      presence of stricture, but the absolute rate of stone recurrence is not
      significantly related to stricture. In the absence of stricture, the rate of
      stone recurrence is higher in patients with dilated intrahepatic duct. Complete
      stone clearance is necessary, because the incidence of recurrent cholangitis or
      cholangiocarcinoma is higher in patients with incomplete clearance of recurrent
      hepatolithiasis.

PMID- 14687813
TI  - Endoscopic ultrasound-guided fine needle aspiration biopsy of patients with
      suspected pancreatic cancer: diagnostic accuracy and acute and 30-day
      complications.
AB  - OBJECTIVES: The aims of this study were to evaluate the diagnostic accuracy of
      endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with
      suspected pancreatic cancer, and to assess immediate, acute, and 30-day
      complications related to EUS-FNA. METHODS: All patients with suspected pancreatic
      cancer were prospectively evaluated. A single gastroenterologist performed all
      EUS-FNAs in the presence of a cytopathologist. Immediate complications were
      evaluated in all patients. An experienced nurse called patients 24-72 h and 30
      days after the procedure. Reference standard for the classification of the final
      diagnosis included: surgery (n = 48), clinical or imaging follow-up (n = 63), or
      death from the disease (n = 47). RESULTS: A total of 158 patients (mean age 62.3
      yr) underwent EUS-FNA during the study period. The mean tumor size was 32 x 26
      mm. The median number of passes was three (range one to 10). Of these patients,
      44% had at least one failed attempt at tissue diagnosis before EUS-FNA. The
      sensitivity, specificity, PPV, NPV, and accuracy of EUS-FNA in solid pancreatic
      masses were 84.3%, 97%, 99%, 64%, and 84%, respectively. Immediate self-limited
      complications occurred in 10 of the 158 EUS-FNAs (6.3%). Of 90 patients contacted
      at 24-72 h, 78 patients (87%) responded. Of the 90 patients, 20 (22%) reported at
      least one symptom, all of which were minor except in three cases (one self
      limited acute pancreatitis and two emergency room visits, one of which led to
      admission). In all, 83 patients were contacted at 30 days, and 82% responded. No
      additional or continued complications were reported. CONCLUSIONS: EUS-FNA is
      highly accurate in identifying patients with suspected pancreatic cancer,
      especially when other modalities have failed. Major complications after EUS-FNA
      are rare, and minor complications are similar to those reported for upper
      endoscopy. It seems that follow-up at 1 wk might capture all of the adverse
      events related to EUS-FNA.

PMID- 14687814
TI  - The accuracy of an endoscopy nurse in interpreting capsule endoscopy.
AB  - OBJECTIVE: The average physician time required to view a wireless capsule
      endoscopy study at our institution is 50 min. It is unknown whether a nurse could
      preview the capsule endoscopy video and accurately detect all significant
      lesions. If so, it may allow the physician to review only the predetected
      abnormalities and thereby greatly reduce physician reading time. Our aim was to
      evaluate whether a nurse can accurately detect lesions on capsule endoscopy.
      METHODS: An endoscopy nurse who was trained to read capsule endoscopy reviewed 20
      consecutive capsule endoscopy studies and recorded all findings. The same studies
      were viewed independently by a gastroenterologist. The two sets of recorded
      findings were reviewed, and a comparison of the accuracy in detecting landmarks
      and clinically significant lesions was made. RESULTS: The nurse missed two of 27
      significant lesions seen by the gastroenterologist (93% sensitivity, 95% CI = 74
      99%), and the gastroenterologist missed three seen by the nurse. The nurse
      accurately recorded gastric emptying time and time of passage through the
      ileocecal valve to within 1 min of the times recorded by the gastroenterologist
      in 18 of 20 patients (90% agreement, 95% CI = 67-98%). CONCLUSIONS: In this
      study, the endoscopy nurse detected 93% of the clinically significant lesions
      seen by the gastroenterologist. The clinical implication of this is that a
      physician extender could preread capsule endoscopies, allowing the
      gastroenterologist to view only the demarcated abnormalities. This could improve
      the cost effectiveness of capsule endoscopy and lead to wider physician
      acceptance of the test.

PMID- 14687815
TI  - Screening for pancreatic exocrine insufficiency in patients with diabetes
      mellitus.
AB  - OBJECTIVES: Fecal elastase 1 (E1) is a relatively sensitive and specific indirect
      test of pancreatic exocrine function. Despite the high functional reserve of the
      pancreas, it is recognized that a significant proportion of diabetic patients may
      also have a deficit of the exocrine function. The aim of this study was to screen
      patients with diabetes mellitus (DM) for pancreatic exocrine insufficiency.
      METHODS: A total of 80 patients were enrolled in this prospective study,
      including 42 patients with DM and 38 nondiabetic controls. Exclusion criteria
      were as follows: age >75 yr; alcohol intake >40 g/day; intake of orlistat or
      acarbose; and history of diarrhea, pancreatitis, GI surgery, immunodeficiency, or
      cancer. All patients underwent the same study protocol, which included clinical
      evaluation, determination of fecal E1, plain x-rays of the abdomen, and abdominal
      ultrasound. An immunoenzymatic method (ScheBoTech, Wettenburg, Germany) was used
      for E1 determination. Diagnosis of pancreatic insufficiency was established for a
      fecal E1 <200 microg/g. RESULTS: The DM and control groups were comparable
      regarding age (62 +/- 10 yr vs 56 +/- 10 yr), sex (18 men and 24 women vs 15 men
      and 23 women), and proportion of patients with excess weight (50% vs 42%).
      Patients had DM diagnosed for 11.5 +/- 8 yr, with structural changes of the
      pancreas detected on ultrasound in three cases and calcifications in one case.
      There was no relationship between E1 determination <200 microg/g and the duration
      or the type of therapy for DM. Fifteen patients (36%) in the DM group had a fecal
      E1 <200 microg/g, compared with two patients (5%) in the control group (p <
      0.05). In the DM group (n = 42), 11 patients with excess weight presented a fecal
      E1 <200 microg/g, whereas four patients with a BMI <25 presented this result (p <
      0.05). CONCLUSIONS: Pancreatic exocrine insufficiency occurs more frequently in
      diabetic patients than in controls. Diabetic individuals with excess weight (BMI
      >25) may be at increased risk for underlying exocrine pancreatic insufficiency.

PMID- 14687816
TI  - Performance of Given suspected blood indicator.
AB  - OBJECTIVES: Given Imaging (Yoqneam, Israel) has developed a suspected blood
      indicator (SBI) function for its wireless capsule endoscopy (WCE) software. The
      SBI detects blood and marks appropriate images for interrogation. The sensitivity
      and accuracy of SBI and its role in examining WCE studies is unknown. Our aim was
      to evaluate the accuracy of this new software in detecting small bowel lesions.
      METHODS: WCE reports of all patients referred for WCE in October and November,
      2002, were reviewed. The images from each patient were reviewed by experienced
      gastroenterologists at 15 frames/s. The findings detected by gastroenterologists
      were compared to those recognized by SBI. Arteriovenous malformations (AVMs),
      ulcers, erosions, and sites of active bleeding were considered significant
      lesions. RESULTS: A total of 24 patients (16 women and eight men, mean age 59 yr)
      were studied during this period. The indications for the study were iron
      deficiency anemia in 18 patients and abdominal pain in six patients. A total of
      109 lesions were identified by gastroenterologists (47 AVMs, 18 active bleeding
      ulcers, 18 ulcers without bleeding, and 26 erosions). Active bleeding seen by
      gastroenterologists was secondary to AVMs (five cases), jejunal ulcers (11 cases,
      all in the same patient), and gastric ulcers (two cases). A total of 31 potential
      areas of blood were identified by SBI. When compared to those findings recognized
      by gastroenterologists, 28 lesions were correctly identified (six AVMs, 13 active
      bleeding ulcers, (three AVMs and 10 jejunal ulcers), seven nonbleeding ulcers,
      and two nonbleeding erosions. The overall sensitivity, positive predictive value,
      and accuracy of SBI to detect significant small bowel lesions were 25.7%, 90%,
      and 34.8%, respectively. If only actively bleeding lesions in the small bowel
      were considered, SBI had sensitivity, positive predictive value, and accuracy of
      81.2%, 81.3%, and 83.3%, respectively. CONCLUSIONS: SBI has good sensitivity and
      positive predictive value for actively bleeding lesions in the small bowel.
      Complete review of the study by the physician is still needed. SBI should be
      considered as a complementary and rapid screening tool for gastroenterologists to
      identify actively bleeding lesions.

PMID- 14687817
TI  - Clinical and imaging features of autoimmune pancreatitis with focal pancreatic
      swelling or mass formation: comparison with so-called tumor-forming pancreatitis
      and pancreatic carcinoma.
AB  - OBJECTIVES: Autoimmune pancreatitis (AIP) with a mass formation or swollen
      pancreas located in one or two segments of the gland (focal type AIP) has been
      reported. The aims of this study were to elucidate the relationship of the
      disease entity between this focal variant and so-called tumor-forming
      pancreatitis (TFP) and to describe the clinical and imaging features
      discriminating focal AIP from pancreatic carcinoma (Pca). METHODS: The clinical,
      radiologic, and pathologic profiles of nine patients with focal AIP were reviewed
      retrospectively and compared with those of 11 patients with alcohol-induced TFP
      and 80 patients with Pca. RESULTS: The patients with focal AIP were predominantly
      older (mean age 64.7 +/- 13.6 yr, range 28-78 yr), male, and presenting with
      obstructive jaundice or focal pancreatic enlargement accompanied by mild
      abdominal symptoms. In comparison, the patients with alcohol-induced TFP who were
      mostly middle-aged (mean age 50.1 +/- 7.95 yr, range 39-62 yr), male, and often
      had attacks of pancreatitis associated with findings of CT scans showing
      pseudocysts or peripancreatic effusion. Focal AIP usually demonstrated no
      abnormalities on pancreatograms downstream from the stricture or obstruction and
      often presented few contrast-filled side branches in the area of main pancreatic
      duct (MPD) stenosis. These characteristics were similar to the imaging features
      of Pca. Significant factors differentiating focal AIP from Pca were lower serum
      levels of CA19-9, homogeneous delayed enhancement evident in dynamic CT scans,
      and ERCP findings exhibiting a longer stenosed MPD and a thinner MPD upstream
      from the stricture. CONCLUSIONS: Focal AIP is associated with clinical and
      radiologic features that are different from those of alcohol-induced TFP. In TFP
      there are two causative factors, namely, AIP and alcohol-induced chronic
      pancreatitis. Differential diagnosis of focal AIP from Pca seems to be possible
      in many cases by evaluating imaging findings such as dynamic CT and ERCP,
      although focal AIP sometimes shows clinical and radiologic features similar to
      those of Pca.

PMID- 14687818
TI  - Cost-effectiveness of N-butyl-2-cyanoacrylate (histoacryl) glue injections versus
      transjugular intrahepatic portosystemic shunt in the management of acute gastric
      variceal bleeding.
AB  - The management of bleeding gastric varices has not been standardized. Although
      transjugular intrahepatic portosystemic shunt (TIPS) is used in most centers,
      endoscopic treatment with N-butyl-2-cyanoacrylate (cyanoacrylate) glue has
      recently been shown to be effective. Cost-effectiveness analyses of these methods
      are lacking. METHODS: We performed a retrospective review of patients with
      bleeding gastric varices treated either by TIPS or cyanoacrylate glue injection.
      Economic analysis was based on direct costs for a fixed financial year. The two
      groups were compared for a period of 6 months follow-up, to liver
      transplantation, or death for each patient. RESULTS: Between January, 1995 and
      December, 1999, 20 patients with bleeding gastric varices had TIPS; 23 patients
      had cyanoacrylate glue injection from January, 2000 to October, 2001. There were
      no significant differences between the two groups in patient characteristics,
      transfusion requirement, and gastric variceal anatomy. In the TIPS group, 15/20
      patients had the procedure performed within 24 h of hemorrhage, and 90% of stent
      insertions were successful. Complications consisted of two cases of pulmonary
      edema, two cases of severe encephalopathy, and a 15% stenosis rate at 6 months.
      In the glue group, there were 3 +/- 1.5 endoscopies and 2 +/- 1 injections per
      patient, with a 96% initial hemostasis. There was one case of (glue) pulmonary
      embolism and one blocked front endoscope lens, which required repair. The initial
      rebleed rate was significantly lower in patients who had TIPS (15% vs 30%, p =
      0.005). The inpatient stay was shorter in the glue group (13 +/- 1 vs 18 +/- 2
      days, p = 0.05), but there was no difference in the overall mortality rate. The
      median cost within 6 months of initial gastric variceal bleeding was $4,138 US
      dollars ($3,009-$8,290 US dollars) for glue versus $11,906 US dollars ($8,200
      $16,770 US dollars) for TIPS (p < 0.0001). CONCLUSION: In this comparable group
      of patients, cyanoacrylate glue injection was more cost effective than TIPS in
      the management of acute gastric variceal bleeding. A prospective, randomized
      trial would be required to confirm our analysis.

PMID- 14687819
TI  - Clinical difficulties in the differentiation of autoimmune pancreatitis and
      pancreatic carcinoma.
AB  - OBJECTIVES: Autoimmune pancreatitis (AIP) is a newly described entity with
      characteristic clinical, histologic, and morphologic changes, in which autoimmune
      mechanisms are involved in pathogenesis. However, difficulties can arise in the
      differentiation of AIP from pancreatic carcinoma. The aims of this study were to
      clarify clinical and radiologic features of AIP to elucidate areas of diagnostic
      confusion. METHODS: Clinical, serologic, and radiologic findings were evaluated
      in 17 patients with AIP. RESULTS: All 17 patients were initially suspected to
      have pancreatic carcinoma. The patients were predominantly elderly men who
      frequently presented with jaundice but without features of acute pancreatitis.
      Elevation of serum gamma-globulin and IgG along with the presence of
      autoantibodies were usually evident, whereas serum tumor markers were elevated in
      54% of cases. Stenosis of the bile duct was detected in 94% of cases. Diffuse
      enlargement of the pancreas and irregular narrowing of the main pancreatic duct
      were radiologically characteristic; however, segmental swelling and narrowing
      were detected in seven and two patients, respectively. In segmental cases,
      neither atrophy of the distal pancreas nor marked upstream dilation of the distal
      main pancreatic duct was observed. Angiographic abnormalities occurred in 54% of
      cases. Serologic and radiologic abnormalities showed considerable improvement
      with steroid therapy. CONCLUSIONS: Frequent stenosis of the bile duct, elevation
      of serum tumor markers, segmental pancreatic enlargement or narrowing of the main
      pancreatic duct, and angiographic abnormalities can cause confusion in the
      differential diagnosis of AIP and pancreatic carcinoma.

PMID- 14687820
TI  - Breath testing to evaluate lactose intolerance in irritable bowel syndrome
      correlates with lactulose testing and may not reflect true lactose malabsorption.
AB  - OBJECTIVES: An increased prevalence of lactose intolerance is seen in irritable
      bowel syndrome (IBS). Recently, we demonstrated a high prevalence of abnormal
      lactulose breath test results in IBS suggesting bacterial overgrowth. Because
      symptoms of lactose intolerance result from bacterial fermentation, the purpose
      of this study was to determine whether an abnormal lactose breath test is
      reflective of malabsorption or early presentation to bacteria. METHODS: Subjects
      with diarrhea-predominant IBS were enrolled. On day 1, subjects underwent a
      lactulose breath test after an overnight fast. Within 1 wk, subjects returned
      after fasting for a lactose breath test with simultaneous blood glucose
      measurements every 15 min to complete a lactose tolerance test (LTT). Symptoms
      were evaluated 3 h after lactose administration. RESULTS: Twenty subjects
      completed the study. One subject inadvertently received dextrose through the
      intravenous and was excluded. Of the remaining 19 subjects, three (16%) had an
      abnormal LTT suggesting malabsorption. In all, 10 subjects (53%) had an abnormal
      lactose breath test, 14 (74%) had an abnormal lactulose breath test, and 11 (58%)
      had symptoms after lactose administration. The agreement with symptoms was
      moderate (kappa = 0.47) and fair (kappa = 0.24) when compared to the lactose
      breath test and LTT, respectively. There was a fair correlation between lactose
      breath test and LTT (kappa = 0.29). However, lactose breath test hydrogen levels
      >166 ppm were universally predictive of abnormal LTT. Finally, a significant
      correlation was seen between the hydrogen production on lactose and lactulose
      breath test (r = 0.56, p = 0.01). CONCLUSIONS: Lactose breath testing in IBS
      subjects does not seem to reflect malabsorption; it may be an indicator of
      abnormal lactulose breath test, suggesting bacterial overgrowth.

PMID- 14687821
TI  - Platelet serotonin transporter in patients with diarrhea-predominant irritable
      bowel syndrome both before and after treatment with alosetron.
AB  - OBJECTIVES: Serotonin reuptake is mediated by a transporter protein (SERT), and
      its dysfunctions can alter serotonergic transmission. The present study examines
      the binding profile of platelet SERT in healthy volunteers as well as in patients
      with diarrhea-predominant irritable bowel syndrome (D-IBS), both before and after
      treatment with the 5-HT(3) receptor antagonist alosetron. METHODS: Binding of
      [(3)H]paroxetine to SERT was assayed in platelet membranes collected from D-IBS
      patients (12 women, age 21-73 yr) and healthy volunteers (12 women, age 24-68
      yr). Both maximal binding capacity (B(max)) and dissociation constant (K(d)) were
      estimated. In D-IBS patients, binding parameters and symptom severity score were
      evaluated at baseline and after treatment with alosetron (1 mg b.i.d. for 8 wk).
      RESULTS: At baseline, B(max) and K(d) values of [(3)H]paroxetine binding were
      respectively lower and higher in D-IBS patients than in healthy volunteers
      (B(max): 518.7 +/- 155.9 vs 1151.9 +/- 187.4 fmol/mg, p < 0.001; K(d): 0.19 +/-
      0.05 vs 0.06 +/- 0.02 nmol/L, p < 0.001). Symptom severity score in D-IBS
      patients (50.9 +/- 18.8) was negatively correlated with B(max) (r = -0.964; p <
      0.001) but not K(d) values (r = -0.164; p = 0.609). After treatment with
      alosetron, symptom severity score decreased significantly (14.4 +/- 3.7; p <
      0.001), whereas B(max) (522.7 +/- 39.7 fmol/mg) and K(d) values (0.17 +/- 0.07
      nmol/L) did not change. CONCLUSIONS: The present results indicate that SERT
      expressed on platelet membranes of D-IBS patients is characterized by low density
      and binding affinity and suggest a possible correlation between the reduced
      capacity of serotonin reuptake and the severity of D-IBS symptoms.

PMID- 14687822
TI  - Risk of early surgery for Crohn's disease: implications for early treatment
      strategies.
AB  - OBJECTIVES: In this study we aimed to define the rate of early surgery for
      Crohn's disease and to identify risk factors associated with early surgery as a
      basis for subsequent studies of early intervention in Crohn's disease. METHODS:
      We assembled a retrospective cohort of patients with Crohn's disease diagnosed
      between 1991 and 1997 and followed for at least 3 yr, who were identified in 16
      community and referral-based practices in New England. Chart review was performed
      for each patient. Details of baseline demographic and disease features were
      recorded. Surgical history including date of surgery, indication, and procedure
      were also noted. Risk factors for early surgery (defined as major surgery for
      Crohn's disease within 3 yr of diagnosis, exclusive of major surgery at time of
      diagnosis) were identified by univariate analysis. Multiple logistic regression
      was used to identify independent risk factors. RESULTS: Of 345 eligible patients,
      69 (20.1%) required surgery within 3 yr of diagnosis, excluding the 14 patients
      (4.1%) who had major surgery at the time of diagnosis. Overall, the interval
      between diagnosis and surgery was short; one half of all patients who required
      surgery underwent operation within 6 months of diagnosis. Risk factors identified
      by univariate analysis as significantly associated with early surgery included
      the following: smoking; disease of small bowel without colonic involvement;
      nausea and vomiting or abdominal pain on presentation; neutrophil count; and
      steroid use in the first 6 months. Disease localized to the colon only, blood in
      the stool, use of 5-aminosalicylate, and lymphocyte count were inversely
      associated with risk of early surgery. Logistic regression confirmed independent
      associations with smoking as a positive risk factor and involvement of colon
      without small bowel as a negative risk factor for early surgery. CONCLUSIONS: The
      rate of surgery is high in the first 3 yr after diagnosis of Crohn's disease,
      particularly in the first 6 months. These results suggest that improved risk
      stratification and potent therapies with rapid onset of action are needed to
      modify the natural history of Crohn's disease.

PMID- 14687824
TI  - Telomere length study in celiac disease.
AB  - OBJECTIVES: Telomeres are important structures that are critical for maintaining
      chromosomal integrity and cell surveillance. The aim of this study was to analyze
      telomere length in patients with celiac disease (CD), a multifactorial disorder
      with a strong genetic component that exhibits genomic instability and cancer
      predisposition, particularly T-cell lymphomas. METHODS: Telomere length measured
      by telomere restriction fragments (TRF) was studied in small intestinal biopsy
      (SIB) samples and peripheral blood lymphocytes (PBL) from 20 untreated CD
      patients, distributed according to the clinical form as four asymptomatic, five
      monosymptomatic, and 11 polysymptomatic individuals. We also analyzed TRF from
      normal peripheral blood lymphocytes and normal biopsy samples as normal controls.
      RESULTS: TRF evaluation showed a significant telomere shortening in SIB samples
      from CD patients (4.21 +/- 0.29 Kb) compared to PBL from the same individuals
      (9.17 +/- 0.35 Kb) (p < 0.0001), independently of clinical form. Mean TRF peak
      values from normal biopsy samples were significantly higher (8.33 +/- 0.38 Kb)
      than those observed in CD biopsy samples (p < 0.001). No differences between TRF
      values in CD-PBL and normal peripheral blood lymphocytes (8.89 +/- 0.37Kb) were
      found. CONCLUSIONS: Our findings in patients with CD, a disorder in which the
      gluten-induced mucosal injury could accelerate telomere shortening, would
      increase the process of end-to-end fusions resulting in chromosomal changes,
      supports the hypothesis that genomic instability and telomere reduction may play
      a role in the cancer predisposition observed in these patients.

PMID- 14687823
TI  - Tropomyosin expression in the ileal pouch: a relationship with the development of
      pouchitis in ulcerative colitis.
AB  - OBJECTIVE: Human tropomyosin isoform 5 (hTM5) is a cytoskeletal protein expressed
      in normal epithelial cells, predominantly in the colon. An autoimmune response
      toward hTM5 has been reported in ulcerative colitis (UC). Whether hTM5 expression
      in the ileum is involved in pouchitis is unknown. We assessed hTM5 expression on
      ileal epithelial cells at surgery and subsequently on development of pouchitis in
      UC. METHODS: In a prospective longitudinal study, 28 UC patients undergoing ileal
      pouch procedures were included. Biopsy samples were taken from the rectum at
      surgery, as well as from the ileal pouch at surgery and at 6 months. The
      specimens were stained by immunoperoxidase using the anti-hTM5 monoclonal
      antibody CG3. Pouchitis was assessed by the Pouchitis Disease Activity Index and
      hTM5 expression on a scale of 0-3. RESULTS: At surgery, in rectal samples, hTM5
      expression was strong in all epithelial cells including the luminal surface,
      whereas in ileal samples hTM5 was not expressed or focally expressed only in the
      goblet cells. At 6 months, the ileum was found to have undergone morphological
      changes, becoming similar to the colon and showing shortening or reduced number
      of villi. These changes were associated with a diffuse hTM5 staining in the
      goblet cells and in the nongoblet epithelial cells lining the crypts and the
      lumen. The hTM5 score was related to the Pouchitis Disease Activity Index at 6
      months (r = 0.82; p = 0.01). CONCLUSIONS: Expression of hTM5 shows a different
      pattern in the ileal pouch in UC after surgery. This event is associated with
      morphological changes of the ileum toward colonic epithelium, related to the
      development of pouchitis.

PMID- 14687825
TI  - Do anal fistulas in Crohn's disease behave differently and defy Goodsall's rule
      more frequently than fistulas that are cryptoglandular in origin?
AB  - OBJECTIVES: The complexity of anal fistulas is different in patients with and
      without Crohn's disease and in men and women. This may affect the localization of
      the internal orifice. We compared the characteristics of anal fistulas and the
      accuracy of Goodsall's rule in predicting the position of the internal orifice in
      male and female Crohn's and non-Crohn's patients. METHODS: A total of 191 fistula
      tracks in 182 consecutive patients (110 men and 72 women) were analyzed
      prospectively. Of the patients, 63 were diagnosed with Crohn's disease. The
      positions of the orifices were recorded and the accuracy of Goodsall's rule
      determined. RESULTS: The distribution of fistula subtypes among Crohn's and non
      Crohn's patients differed significantly (p = 0.0471). Fistulas with an anterior
      external opening occurred more frequently in Crohn's patients (p = 0.0350) and in
      women (p = 0.0030). Fistulas with a posterior external orifice were observed more
      frequently in non-Crohn's patients (p = 0.0350) and in men (p = 0.0028). Overall,
      Goodsall's rule performed less well in women compared with men (p = 0.0633). The
      accuracy of Goodsall's rule overall was not affected by Crohn's disease. In
      female non-Crohn's patients, the positive predictive value of a posterior
      external orifice was lower than in men (p = 0.0406). CONCLUSIONS: The
      distribution of fistula subtypes and the ratio of anterior and posterior external
      openings among Crohn's and non-Crohn's patients differ significantly. Many
      fistulas defy Goodsall's rule, particularly in women and when applied to fistulas
      with anterior external orifices. The popular rule, however, falls equally short
      in Crohn's and non-Crohn's fistulas.

PMID- 14687826
TI  - Long-term efficacy of sertraline as a treatment for cholestatic pruritus in
      patients with primary biliary cirrhosis.
AB  - OBJECTIVES: Generalized pruritus is a common complication of cholestatic liver
      diseases, although its pathogenesis remains elusive. Current treatments are often
      inadequate and may be poorly tolerated, so the clinician is sometimes faced with
      a patient in misery and no good therapeutic options. Because, in our experience,
      several patients with primary biliary cirrhosis (PBC) claimed that sertraline had
      improved their pruritus, we sought to determine whether sertraline use was
      associated with changes in pruritus medications or self-reported severity of
      pruritus in a large cohort of patients with PBC. METHODS: The self-reported
      severity of pruritus was followed prospectively in 40 patients with PBC for a
      mean of 7.5 +/- 1.3 yr. These data were then retrospectively examined to
      determine the effect of sertraline on pruritus in all subjects who had received
      sertraline at some time during the study. RESULTS: For 28 of 32 patients with
      pruritus, itching was stable or fluctuated slightly over the follow-up period. No
      patient experienced rapid progression of pruritus, and four patients experienced
      a sustained resolution of their pruritus. Ten subjects started sertraline and
      continued it long enough (>6 months) to determine its lasting effect on pruritus.
      Three of these individuals did not have significant pruritus before or after
      sertraline. Of the seven patients with pruritus, six (86%) recorded a significant
      reduction or resolution of pruritus in their weekly diaries and also decreased or
      completely stopped other medications for pruritus. CONCLUSIONS: Sertraline use is
      associated with an improvement in cholestatic pruritus. This novel observation
      implies that serotonergic fibers are important in regulating the perception of
      itch.

PMID- 14687827
TI  - Measuring the hemodynamic response to primary pharmacoprophylaxis of variceal
      bleeding: a cost-effectiveness analysis.
AB  - OBJECTIVES: The hemodynamic response to ss-blockers alone or with nitrates is
      highly predictive of efficacy in prevention of variceal bleeding. Hemodynamic
      monitoring (HDM) requires catheterization of the hepatic vein and measurement of
      the hepatic venous pressure gradient, the difference between wedged and free
      hepatic venous pressure. The aim of this study was to compare HDM with no HDM in
      patients considered for primary pharmacoprophylaxis of esophageal variceal
      bleeding. METHODS: A decision model was constructed to compare HDM with no HDM in
      cirrhotic patients with moderate to large esophageal varices. Patients intolerant
      to beta-blocker therapy would undergo endoscopic variceal ligation; those with an
      inadequate hemodynamic response (HDR) to beta-blocker therapy could have nitrates
      added before ligation was considered. Variceal bleeding was treated with
      ligation, with transjugular intrahepatic portosystemic shunt (TIPS) reserved for
      refractory bleeding. Probabilities of treatment responses as well as risks of
      bleeding and mortality were based on published literature. Only direct costs were
      considered during the 5-yr time horizon. Outcomes were cost in United States
      dollars, survival length in life-years, and proportions of patients who
      experienced variceal bleeding, TIPS insertion, and mortality from any cause.
      RESULTS: In the base case analysis, HDM was either cost-saving ($2,523 US dollars
      /life-year gained) or cost-effective (incremental cost-effectiveness ratio of
      $5,200 US dollars/life-year saved) compared with no HDM, depending on whether
      nitrates were added to beta-blocker therapy. HDM reduced variceal bleeding by
      nearly 60% and had a small effect on all-cause mortality. In the sensitivity
      analysis, HDM was sensitive to the time horizon, as it was not cost-effective for
      a time horizon of <22 months and was not cost-saving before 49 months. The cost
      effectiveness of HDM was not sensitive to reasonable variation in the probability
      of HDR to beta-blocker therapy, risk of bleeding, risk reduction with
      pharmacotherapy, or to the costs of HDM, bleeding, ligation, or TIPS.
      Probabilistic sensitivity analysis indicated that HDM was more effective and less
      costly 100% and 57% of the time, respectively. CONCLUSIONS: Compared with the
      current standard of no HDM, measuring the hemodynamic response of primary
      pharmacoprophylaxis substantially reduces the number of bleeding episodes and is
      cost-effective or cost-saving over a wide range of sensitivity analyses. A
      randomized trial of HDM is needed to verify its efficacy in clinical practice.

PMID- 14687828
TI  - Tumor necrosis factor-alpha-induced insulin resistance may mediate the hepatitis
      C virus-diabetes association.
AB  - OBJECTIVES: Among patients infected with hepatitis C virus (HCV), 13-33% develop
      type 2 diabetes mellitus (DM). The mechanism for this remains unclear. Because
      tumor necrosis factor-alpha (TNF-alpha) has been identified as a mediator of
      insulin resistance and is induced by HCV, we examined TNF-alpha and
      proinflammatory cytokines in noncirrhotic patients with chronic hepatitis C, both
      with and without diabetes. METHODS: HCV-infected patients with type 2 DM (n = 23)
      were compared with age- and sex-matched patients with chronic hepatitis C and
      without DM (n = 28), patients with DM and without HCV (n = 31), and healthy
      controls (n = 21). Serum levels of TNF-alpha, interleukin-1beta (IL-1beta),
      interleukin-6 (IL-6), and soluble TNF receptors (sTNFR) 1 (p55) and 2 (p75) were
      determined by ELISA. RESULTS: Detectable serum TNF was found in 74% of the HCV/DM
      patients, versus 64% of the nondiabetic HCV group and < or =10% in the other
      groups. Mean sTNFR1 in the HCV/DM group was 1931 pg/ml (95% CI = 1449-2413),
      compared with 1289 pg/ml (95% CI = 1101-1476) in nondiabetic HCV patients, with
      similar values in the other two groups (p = 0.001). The mean sTNFR2 level in the
      HCV/DM patients was 3326 pg/ml (95% CI = 2924-3727) compared with 2367 pg/ml (95%
      CI = 1951-2784) in the nondiabetic HCV patients, and similar results in the other
      groups (p < 0.0001). Serum IL-1beta, IL-6, and C-reactive protein were not
      significantly different between HCV patients with or without DM. CONCLUSIONS:
      Excessive TNF-alpha response characterizes HCV-infected patients who develop DM.
      STNFR may be a marker for the development of DM in chronic hepatitis C.

PMID- 14687829
TI  - Primary biliary cirrhosis and hepatitis C virus infection.
AB  - OBJECTIVE: The aim of this study was to describe the clinical characteristics of
      hepatitis C virus (HCV)-infected patients with primary biliary cirrhosis (PBC) by
      comparison to patients with both antimitochondrial (AMA) positive and AMA
      negative PBC. METHODS: All patients consecutively diagnosed as having PBC between
      1973 and 1999 who had a regular follow-up of at least 2 yr were prospectively
      included in the study. The mean follow-up was 8.3 +/- 5.7 yr. Survival was
      calculated according to Kaplan-Meier curves. RESULTS: A total of 170 patients
      with PBC were considered. The syndrome with PBC and HCV infection (HCV-infected
      PBC patients) was recorded in 14 patients (13 women and one man), whereas 135
      patients had AMA positive PBC and 18 had AMA negative PBC. Only three patients
      fulfilled the criteria for overlap syndrome involving PBC and autoimmune
      hepatitis. At presentation, the HCV-infected PBC group had significantly lower
      levels of ALP, gamma-glutamyl transpeptidase, and IgM than the AMA positive or
      AMA negative PBC patients (p < 0.01). With regard to the autoantibody profile,
      there was a significant association with LKM and HCV-infected PBC patients
      (21.4%), whereas ANA was significantly higher in AMA negative PBC patients than
      in the other two groups (83% vs 21.4% in the HCV-infected PBC patients and 38.5%
      in the AMA positive PBC group). No differences were found regarding the
      association with autoimmune conditions. During follow-up, hepatocellular
      carcinoma (HCC) developed more frequently in the PBC/HCV overlap group (i.e.,
      three of 14 vs four of 135 patients with AMA positive PBC, p < 0.05). Survival
      curves were similar in HCV-infected PBC patients and AMA positive PBC, whereas
      the AMA negative group had a significantly slower decline (relative risk (RR) =
      2.44, p < 0.05). CONCLUSION: HCV-infected PBC patients are characterized by a
      biochemical profile with a modest rise in cholestatic enzymes but a high risk of
      developing HCC during follow-up.

PMID- 14687830
TI  - Charcoal-based hemodiabsorption liver support for episodic type C hepatic
      encephalopathy.
AB  - OBJECTIVES: Episodic (acute) type C hepatic encephalopathy (AHE) fails to respond
      to 5 days of medical therapy in 10-30% of patients and carries a 10-30% mortality
      rate. We prospectively studied extracorporeal liver support for AHE failing to
      respond to medical therapy to assess its safety and efficacy and the role of
      anticoagulation. METHODS: A series of patients with cirrhosis and AHE failing to
      respond to at least 24 h of medical therapy underwent a maximum of three 6-h
      charcoal-based hemodiabsorption (Liver Dialysis Unit) treatments. A standard
      anticoagulation protocol, with heparin dosing based on activated clotting time
      (ACT) determinations, heparin dose-response curve, and target ACT of 275-300 s,
      was developed. Therapy was terminated if patients met a predetermined clinical
      response, deteriorated, or underwent transplantation. RESULTS: Eighteen patients
      with grade 2-4 AHE despite 5.9 +/- 3.9 days of medical therapy underwent a mean
      of 1.6 treatments. In 2.6 +/- 1.9 days, 16 patients (88.9%) improved to less than
      grade 2 HE or achieved at least a 50% hepatic encephalopathy index (HEI)
      reduction. Median mental status (grade 2 vs 1, p < 0.05) and HEI (0.634 +/- 0.194
      vs 0.363 +/- 0.263, p < 0.005) improved significantly. Survival was 94.4% and
      72.2% at 5 and 30 days, respectively. Use of our developed anticoagulation
      protocol resulted in less platelet (14.2% +/- 2.8% vs 32.5% +/- 5.8%, p < 0.005)
      and fibrinogen consumption (12.1% +/- 3.5% vs 43.3% +/- 8.6%, p < 0.0005) and
      blood product use (6.2 +/- 1.8 vs 19.0 +/- 5.6 units, p < 0.05) compared with
      treatments according to manufacturer's guidelines. CONCLUSIONS: Charcoal-based
      hemodiabsorption treatments in which a standardized anticoagulation protocol is
      used is safe and effective treatment for AHE not responding to standard medical
      therapy.

PMID- 14687831
TI  - Does leptin play a role in the pathogenesis of human nonalcoholic
      steatohepatitis?
AB  - OBJECTIVES: Obesity is a risk factor for nonalcoholic steatohepatitis (NASH).
      Leptin plays an important role in the regulation of food intake, body
      composition, energy expenditure, and body weight. It has been suggested that
      leptin plays a role in the pathogenesis of NASH; however, adequate studies are
      lacking. We therefore conducted a study to explore the role of serum leptin in
      the pathogenesis of human NASH. METHODS: We measured the levels of serum leptin
      and its anthropometric, biochemical, metabolic, and histological correlates in a
      cohort of patients with NASH (n = 26) and well-matched controls (n = 20).
      Furthermore, we measured the levels of leptin in the serum and hepatic leptin and
      leptin receptor messenger RNA (mRNA) expression in liver biopsy specimens of
      patients with NASH (n = 5) and simple steatosis (n = 5). RESULTS: Serum leptin
      was not statistically different between patients with NASH and their controls (21
      +/- 13 vs 18 +/- 11 ng/ml, respectively, p = 0.5). There was no correlation
      between serum leptin and hepatic histology, serum transaminases, fasting insulin
      levels, or a measure of insulin resistance. After adjusting for covariates in a
      multiple regression analysis, only percent body fat (p = 0.04) and subcutaneous
      abdominal fat area (p = 0.04) had significant correlation with serum leptin.
      There was no expression of leptin mRNA in the cell lysate of liver biopsy
      specimens of subjects with NASH or steatosis. Additionally, the serum leptin
      levels and the hepatic leptin receptor mRNA expression were not statistically
      different between patients with NASH and those with simple steatosis. CONCLUSION:
      These data do not support a direct role for leptin in the pathogenesis of human
      NASH.

PMID- 14687832
TI  - Prevalence of colorectal neoplasia in smokers.
AB  - OBJECTIVES: Smoking has been linked with colorectal neoplasia. Previous
      colonoscopy screening studies have omitted smoking and have examined only gender,
      age, and family history. Our aim was to use a screening population to measure the
      prevalence of neoplasia in smokers, the anatomic location of these lesions, and
      the strength of this association relative to other risk factors. METHODS: Data
      collected from the charts of 1988 screening colonoscopy patients included colonic
      findings, histology, risk factors for colorectal neoplasia, and smoking pattern.
      Current smokers were defined as those who had smoked more than 10 pack-years and
      were currently smoking or who had quit within the past 10 yr. Our outcomes were
      any adenomatous lesion and significant colonic neoplasia, which included
      adenocarcinoma, high grade dysplasia, villous tissue, large (>1 cm) adenomas, and
      multiple (more than two) adenomas. RESULTS: Multivariate analysis revealed that
      current smokers were more likely to have any adenomatous lesion (odds ratio [OR]
      = 1.89; 95% CI = 1.42-2.51; p < 0.001) as well as significant neoplasia (OR =
      2.26; 95% CI = 1.56-3.27; p < 0.001) than those who had never smoked. The
      increased risk for smokers was predominantly for left-sided neoplasia. The risk
      for significant neoplasia was greater for smokers than for patients with a family
      history of colorectal cancer (OR = 1.20; 95% CI = 0.75-1.92; p > 0.05).
      CONCLUSIONS: Smoking is a significant risk factor for colorectal neoplasia in a
      screening population, especially for significant left-sided lesions. In our
      sample population, smoking posed a greater risk than family history of colorectal
      cancer.

PMID- 14687833
TI  - Does the use of 5-aminosalicylates in inflammatory bowel disease prevent the
      development of colorectal cancer?
AB  - OBJECTIVES: There is increased interest in determining whether 5-aminosalicylate
      (5-ASA) use can prevent the development of colorectal cancer (CRC) among patients
      with inflammatory bowel disease (IBD). The aim of this study was to determine
      whether use of 5-ASA was associated with a reduced risk of CRC in these patients.
      METHODS: We extracted from our population-based University of Manitoba
      Inflammatory Bowel Disease Epidemiology Database the number of patients with a
      new diagnosis of CRC between the years 1997 and 2000. From within our
      Inflammatory Bowel Disease Epidemiology Database we extracted a control group of
      IBD patients who did not develop CRC matched to the case group who did develop
      CRC by age, sex, diagnosis, year of diagnosis, and geographic area of residence.
      We linked cases and controls with Manitoba Health's Drug Program Information
      Network to study 5-ASA use within 2 yr before CRC diagnosis. The Drug Program
      Information Network database is a population-based database that was established
      in 1995 and that records all prescription drugs. RESULTS: There were 25 cases of
      IBD identified as having CRC. These were matched with 348 cases of IBD who did
      not develop CRC. CRC cases were more likely to be exposed to 5-ASA (odds ratio =
      1.46; 95% CI = 0.58-3.73) but this result was not statistically significant. The
      mean total days of use was 400.9 days +/- 185.9 among CRC cases versus 420.2 days
      +/- 241.7 among non-CRC cases (p = 0.92). The prescribed daily dose was 2295
      mg/day +/- 1041 mg among CRC cases and 1811 mg +/- 520 mg among controls (p =
      0.21). CONCLUSIONS: These data do not support 5-ASA as protective in preventing
      CRC.

PMID- 14687834
TI  - Primary hepatic non-Hodgkin's lymphomas: case report and review of the
      literature.
AB  - A 31-yr-old man presented with a 1-wk history of fever, chills, weakness,
      headaches, and a significant 20-lb weight loss over the preceding 2 months. His
      past medical history was relevant for liver amebiasis during childhood. Two days
      before admission, the patient noticed jaundice. He denied abdominal pain or other
      GI symptoms, and there was no history of alcohol intake, medications, or illicit
      drugs. His physical examination revealed generalized jaundice,
      hepatosplenomegaly, and bilateral leg edema. Neurologically, the patient was
      agitated, with periods of disorientation, and he had bilateral flapping. His
      blood tests revealed pancytopenia, renal failure, liver failure, and
      coagulopathy. Because the patient had a fever, hepatosplenomegaly, and
      pancytopenia, a further workup also included a bone marrow and liver biopsy. No
      conclusive diagnosis could be made from the above tests, and the patient died 5
      days after admission. Postmortem evaluation, including flow cytometry and gene
      rearrangement in the tissue obtained from the liver, revealed large B cell
      lymphoma. This case illustrates an unusual presentation of hepatic non-Hodgkin's
      lymphoma. Current information regarding this entity is scant, mainly owing to its
      rarity. We present a review of the literature, including the incidence,
      presentation, treatment, and prognosis of primary hepatic lymphoma.

PMID- 14687835
TI  - Re: Mortality and follow-up colonoscopy after colorectal cancer.

PMID- 14687837
TI  - Betaine and nonalcoholic steatohepatitis.

PMID- 14687838
TI  - Dosage of intravenous pantoprazole.

PMID- 14687839
TI  - Colon lavage-induced ileocecal valve ulceration.

PMID- 14687841
TI  - Tonsillectomy and risk of acute appendicitis.

PMID- 14687842
TI  - Patent accessory pancreatic duct prevents acute pancreatitis.

PMID- 14687843
TI  - The association between mannan-binding lectin gene alleles and celiac disease.

PMID- 14687844
TI  - Spontaneous resolution of a pancreatic-colonic fistula after acute pancreatitis.

PMID- 14687845
TI  - Complications after outpatient upper GI endoscopy in children: 45-day follow-up.

PMID- 14687846
TI  - Autoimmune pancreatitis is a systemic autoimmune disease.

PMID- 14687848
TI  - What's a disease?

PMID- 14687847
TI  - Complications of infliximab therapy in children and adolescents affected by
      Crohn's disease.

PMID- 14687849
TI  - Celiac disease and small intestinal tubulovillous adenoma: a role for push
      enteroscopy?

PMID- 14687850
TI  - Sleep apnea obstructive syndrome: a new complication previously undescribed in
      cirrhotic patients with ascites.

PMID- 14687851
TI  - The peculiarity of the right-hemisphere function in depression: solving the
      paradoxes.
AB  - Depression is characterized by functional insufficiency of the right hemisphere
      combined with its physiological overactivation. This paradox can be solved in the
      frame of the general concept of brain laterality. According to the present
      assumption, the left hemisphere organizes any information in an unambiguous
      monosemantic context, and this process requires an additional activation of the
      brain cortex in order to restrict natural relationships between objects and
      events. On the contrary, the right hemisphere organizes any information in the
      polysemantic context based on the simultaneous capture of the numerous natural
      relationships between elements of information. In healthy creative subjects this
      process does not require additional physiological activation of the cortex. In
      depression the physiological overactivation of the right hemisphere reflects the
      unsuccessful effort to overcome its functional insufficiency.

PMID- 14687852
TI  - Risperidone in acute and long-term therapy of schizophrenia--a clinical profile.
AB  - Data from a range of well-controlled clinical trials, observational studies, and
      clinical use support the efficacy of risperidone for both acute and long-term
      therapy of schizophrenic psychoses. With regard to positive symptoms, the
      efficacy of risperidone was shown to be at least comparable with that of
      haloperidol. However, risperidone differs from conventional antipsychotics
      because it is more effective against the negative symptoms, has beneficial
      effects on affective and cognitive symptoms, and carries less risk of
      extrapyramidal side effects (EPS). To date, risperidone is the only atypical
      antipsychotic to have shown a significantly lower relapse rate compared with
      haloperidol in a long-term double-blind trial. This review describes
      comprehensive trial data and therapeutic observations gained with risperidone in
      the treatment of schizophrenia since its approval.

PMID- 14687853
TI  - Protection against beta-amyloid peptide-induced memory impairment with long-term
      administration of extract of Angelica gigas or decursinol in mice.
AB  - We investigated the effect of long-term oral administration of ethanolic extract
      of Angelica gigas Nakai (Umbelliferae) (EAG) or decursinol, a coumarin isolated
      from A. gigas, on beta-amyloid peptide 1-42 (Abeta(1-42))-induced memory
      impairment in mice. Mice were allowed free access to drinking water (control) or
      water containing different concentrations of EAG. After 4 weeks, Abeta(1-42) (410
      pmol) was administered via intracerebroventricular injection. Pretreatment of
      mice with EAG (0.1%) for 4 weeks significantly blocked the Abeta(1-42)-induced
      impairment in passive avoidance performance. Next, mice were fed with chow mixed
      with various doses of decursinol for 4 weeks before intracerebroventricular
      injection of Abeta(1-42) (410 pmol). Pretreatment of mice with decursinol
      (0.001%, 0.002%, and 0.004%) for 4 weeks significantly attenuated the Abeta(1-42)
      induced impairment in passive avoidance performance. Decursinol (0.004%) also
      significantly blunted the Abeta(1-42)-induced decrease in alternation behavior
      (spatial working memory) in the Y-maze test without change in general locomotor
      activity. These findings suggest that EAG or decursinol may have preventive
      effect against memory impairment related with Abeta of Alzheimer's disease.

PMID- 14687854
TI  - Lack of efficacy of a nicotine transdermal treatment on motor and cognitive
      deficits in Parkinson's disease.
AB  - Studies assessing the efficacy of nicotine in Parkinson's disease (PD) have
      generated contradictory results. The controversy seems to stem from uncontrolled
      factors including the lack of objective measures, the practice effect in a test
      retest design, and the absence of plasmatic dosage. This study aimed at further
      controlling these factors using transdermal nicotine in PD. METHODS: Twenty-two
      nonsmoking PD patients received a transdermal nicotine treatment over 25 days in
      increasing titrated doses. Motor and cognitive assessments were carried out on
      days 11 and 25 (low-dose and high-dose assessments, respectively) and after a 14
      day washout period. RESULTS: Patients tolerated nicotine poorly. Thirteen (59%)
      withdrew, mostly because of acute side effects. In the remaining nine patients,
      nicotine neither improved nor worsened motor or cognitive functioning in
      comparison with 10 age, gender and education matched controls. CONCLUSIONS:
      Transdermal nicotine is not effective in treating motor and cognitive deficits in
      PD. The results obtained with our objective measures confirm a recent double
      blind, placebo-controlled study that used clinical measures. It is possible that
      nicotine lacks specificity in targeting critical nicotinic receptors that might
      be involved in PD pathophysiology. The low tolerability may be related to such a
      lack of specificity of nicotine, which would directly stimulate the autonomic
      nervous system.

PMID- 14687855
TI  - Activation of protein kinase B (Akt) signaling after electroconvulsive shock in
      the rat hippocampus.
AB  - Akt (protein kinase B, PKB) is one of the major downstream pathways of
      neurotrophin signaling and plays important roles in the cell survival and
      synaptic plasticity of the central nervous system. Electroconvulsive shock (ECS)
      has neurotrophic effect and it affects the synaptic plasticity. It can activate
      another major pathway of neurotrophin signaling, i.e., Ras-Raf-MEK-Erk cascade.
      In this paper, the authors investigated whether ECS can activate Akt signaling in
      the rat hippocampus. After a single ECS, the phosphorylation of Akt was
      increased, as were the signals detected by phospho-PDK1 substrate antibody, which
      suggests the activation of PDK1, an upstream molecule of Akt. The phosphorylation
      of downstream molecules of Akt, forkhead transcription factors (FKHR),
      endothelial nitric oxide synthase (eNOS), and glycogen synthase kinase-3beta (GSK
      3beta) was also increased. The increased phosphorylation of Akt appeared within 5
      min of ECS and its time frame paralleled that of the phosphorylation of Erks.
      Taken together, these results suggest that ECS activates Akt signaling over a
      similar time scale to that of Erks in the rat hippocampus.

PMID- 14687856
TI  - L-type Ca2+ channels mediate cardiovascular symptoms of alcohol withdrawal in
      humans.
AB  - The cardiovascular effects and plasma concentrations after intravenous verapamil
      injection (5 mg) were compared in seven alcohol dependents during alcohol
      withdrawal syndrome (AWS) to those after resolution of these symptoms. At the
      onset of AWS, verapamil caused a bradycardiac response, which was absent after
      resolution of AWS. At the same period, a hypotensive effect of verapamil was
      weakened. No differences in verapamil plasma concentrations were observed between
      different periods. These results suggest that L-type Ca(2+) channels are involved
      in mediating cardiovascular symptoms of AWS.

PMID- 14687857
TI  - Commercially available Hypericum perforatum extracts do not decrease immobility
      of rats in the forced swimming test.
AB  - There are controversial results of clinical trials on the antidepressant effects
      of Hypericum perforatum, while several preclinical studies describe
      antidepressant properties for Hypericum extracts. This study evaluates the
      antidepressant effect of two commercially available hydroalcoholic extracts of H.
      perforatum standardized to contain 0.3% hypericin in comparison to imipramine
      (IMI), in the forced swimming test (FST). Wistar rats were treated with different
      doses of two Hypericum extracts, of hypericin or of IMI and submitted to the FST.
      The experiments were videotape recorded to detail immobile and active behaviors
      of rats during the procedures. The imported extract tested and hypericin did not
      modify rats' behaviors in the test, while IMI, a classical antidepressant,
      significantly shortened immobility and prolonged climbing behavior during forced
      swimming. The locally produced Hypericum extract significantly increased
      immobility duration as compared to the controls at the same time as climbing
      efforts were decreased. Therefore, the two different commercially available
      Brazilian hydroalcoholic H. perforatum extracts did not show the expected effects
      in a screening test for antidepressant agents, on the contrary, one of the
      extracts promoted a depressant-like effect in rats. Therefore, these extracts
      available to the population differ from other Hypericum extracts. At which step
      of the production or commercialization chain these extracts probably lost their
      therapeutic potential remains to be evaluated.

PMID- 14687858
TI  - Gender differences in treatment response to sertraline versus imipramine in
      patients with nonmelancholic depressive disorders.
AB  - There is evidence of gender differences in depressive disorders in terms of
      epidemiology and clinical manifestations. However, few studies have addressed the
      gender differences in terms of antidepressant treatment response in clinical
      practice. The aim of this study was to examine gender differences in the acute
      antidepressant response to sertraline and imipramine in nonmelancholic depressive
      disorders. A total of 239 patients with nonmelancholic major depression or
      dysthymia (DSM-III-R) and a score of >/=18 at baseline on the Hamilton Depression
      Rating Scale (HAM-D) were randomised in a 1:1 ratio treatment with flexible doses
      of sertraline (50-200 mg/day) or imipramine (75-225 mg/day) for 8 weeks in a
      multicenter, randomised, open-labeled, parallel group comparative trial.
      Depressive and anxiety symptoms were assessed using the HAM-D and the Hamilton
      Anxiety Rating Scale (HAM-A). Using HAM-D criteria, women were significantly more
      likely to respond to sertraline than to imipramine (72.2% vs. 52.1%, P=.008),
      whilst men respond similarly to sertraline and to imipramine (56.5% vs. 59.3%,
      P>.05). Response analysis based on HAM-A shows similar results (women: 68.9% vs.
      43.6%, P=.001; men: 56.5% vs. 51.9%, P>.05). Women taking sertraline show
      statistically significant higher reductions in HAM-D, HAM-A, and in CGI-S than
      women taking imipramine. The proportion of women who dropped out due to adverse
      events was much lower in sertraline than in imipramine (10.9% vs. 27.8%, P=.006),
      with no differences between treatments in men (8.3% vs. 11.5%, P>.05). It was
      concluded that sertraline is more effective and better tolerated than imipramine
      in the acute treatment of nonmelancholic depressive disorders in women, whereas
      men responded similarly to sertraline and to imipramine.

PMID- 14687859
TI  - Effects of lithium and valproate on agonist-induced platelet intracellular
      calcium mobilization: relevance to myosin light chain kinase.
AB  - Serotonin (5-HT)- or thrombin-stimulated platelet intracellular calcium (Ca)
      mobilization has been reported to be enhanced in patients with bipolar disorders.
      However, the mechanism of this enhancement is unknown. As a preliminary study,
      the authors examined the effects of a myosin light chain kinase (MLCK) inhibitor,
      1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML
      9), and two drugs that are mainstays of treatment for bipolar disorder, lithium
      and valproate, on 5-HT- or thrombin-induced Ca increase in the platelets of
      normal subjects. When preincubated with 30 microM ML-9, Ca responses to both
      agonists were enhanced. Valproate showed a dose-dependent attenuation of agonist
      induced intracellular Ca rise, both in the absence and presence of ML-9. Although
      lithium alone had no significant effect on the Ca increase, a high concentration
      of lithium significantly decreased Ca mobilization only in the presence of ML-9.
      These results suggest that the enhanced Ca response observed in bipolar disorder
      might be relevant to decreased function of MLCK and that the mechanism of action
      of lithium may include a compensatory effect on MLCK modulation.

PMID- 14687860
TI  - EEG spectral power and mean frequencies in early heroin abstinence.
AB  - The purpose of the present study was to investigate cumulative heroin effects on
      brain functioning by studying relationships among electroencephalography (EEG)
      spectral power and mean frequencies and heroin abuse history. Eyes-closed resting
      EEG data were collected from the 19 monopolar electrode sites in 33 heroin
      abusers and 13 age-matched healthy volunteers. The mean age of the patients was
      23.1+/-4.5 years, the duration of daily heroin abuse (DDHA) ranged from 4 to 44
      months, the intravenous doses of heroin ranged from 0.04 to 1.00 g/day, the
      abstinence length ranged from 6 days to 4.5 months. General linear model (GLM)
      repeated measures procedure revealed a significant group effect on the
      distribution of the mean power spectrum between bands and mean frequencies in
      almost all analyzed derivations. Further analysis demonstrated that these
      intergroup differences were diversely related to at least three aspects of heroin
      taking history. Frequency shifts in alpha2 range, most prominent in frontal and
      central derivations, were related to duration of daily heroin consumption.
      Slowing of alpha1 mean frequency, most prominent in central, temporal, and
      occipital derivations, was registered mainly in heroin addicts who abused high
      doses of the drug. Spectral power characteristics of brain electrical activities
      in our patient population were strongly predicted by abstinence length. The
      present results give grounds to suppose that chronic heroin-taking induces
      neuronal oscillation frequency changes, which may contribute to the development
      of antisocial trends and some semantic processes disturbances in these patients.
      Supplementary neurophysiological deficit is characteristic for heroin addicts who
      takes high doses of the drug, however, its relation to heroin abuse remains
      unclear. Pronounced desynchronization is observed in acute heroin withdrawal, and
      spectral power characteristics tend to normalize almost completely during several
      weeks of abstinence.

PMID- 14687861
TI  - Suicide and occupation: further supportive evidence for their relevance.
AB  - In recent years, the relationship between occupation and suicide has been
      extensively investigated, but few definite conclusions regarding the nature of
      the relationship have been established. In the present study, this relationship
      was investigated by examining Japanese governmental statistics. First,
      correlations of suicide rate relative to industry categories were examined
      individually for primary industry (farmers, fishermen, and forest workers),
      secondary industry (construction workers, manufacture works, and miners), and
      tertiary industry (indoor workers) for all of the 47 prefectures of Japan.
      Second, in the industries that showed a significant correlation with suicide
      rate, the relationship to other factors was adjusted using possibly confounding
      factors. As a result, suicide rate was positively correlated with primary
      industry percentage, but not with secondary or tertiary industry percentages.
      Multiple regression analysis showed that suicide rate was positively associated
      with primary industry percentage with significant tendency while it was
      significantly and negatively associated with annual total sunshine. Limitations
      are that individual suicide rates according to occupational types were not
      available and direct correlations with the above variables could not be
      investigated. The present findings suggest a possibility that occupational
      factors associated with primary industry may be relevant to suicide, and that,
      additionally, annual total sunshine may affect suicide independently. Since
      workers with primary industry are likely to be exposed to sunshine than other
      workers, they may tend to be more affected by the decrease of annual total
      sunshine.

PMID- 14687862
TI  - Combination of "atypical" antipsychotic medication in the management of treatment
      resistant schizophrenia and schizoaffective disorder.
AB  - BACKGROUND: This article reviews the published clinical data on treatment
      resistant schizophrenic and schizoaffective patients managed with combinations of
      "atypical" antipsychotic medication. METHOD: A computerized MEDLINE literature
      search covering an 18-year period (1985-2003) was conducted. All pertinent papers
      on the subject of the use of combination "atypical" antipsychotic medication in
      the management of treatment-resistant schizophrenia and schizoaffective disorder
      were obtained with subsequent analysis and discussion of the retrieved data.
      RESULTS: The search identified 29 case reports and case series reports (172
      patients) and one double-blind placebo-controlled trial (28 patients) describing
      the use of combination "atypical" antipsychotic medication (clozapine
      risperidone; clozapine-sulpiride; clozapine-olanzapine; clozapine-quetiapine;
      olanzapine-sulpiride; olanzapine-quetiapine; risperidone-olanzapine; risperidone
      quetiapine) in the treatment of resistant schizophrenic and schizoaffective
      patients. An overview of results suggests that the combinations were beneficial
      in the described patients with reduction of positive symptoms and occasionally
      negative symptoms. Significant adverse effects, while rare, were reported in a
      few cases and did not appear to different in nature from those managed on
      monotherapeutic regimens. CONCLUSION: Combinations of "atypical" antipsychotic
      medications are well tolerated and may be effective in the management of
      treatment refractory schizophrenia and schizoaffective disorder. However, further
      double-blind placebo-controlled trials are required in order to test and confirm
      these observations.

PMID- 14687863
TI  - The comparison of nail and serum trace elements in patients with epilepsy and
      healthy subjects.
AB  - The objective of this prospective study was to determine the levels of manganese
      (Mn), copper (Cu), and zinc (Zn) levels in both nail and serum from patients with
      epilepsy. For this purpose, levels of these elements were measured in 31 patients
      with epilepsy and 19 healthy subjects. Element analyses were carried out by
      atomic absorption spectrophotometer (AAS). Increased Mn levels were detected in
      nail of patients with epilepsy compared to healthy controls (P<.008). The main
      nail Zn and Cu levels were found to be unchanged in epileptic patients compared
      to control subjects. There were no significant differences in serum Mn and Zn
      levels between epileptic patients and control subjects. However, there was a
      statistically significant increase in serum Cu levels in patients with epilepsy
      in comparison with control group (P<.009). Our results demonstrate that some
      trace element levels may vary in epileptic patients, and because of the more
      stable status, the analysis of these element levels in some tissues such as nail
      might be superior to serum analysis.

PMID- 14687864
TI  - Anticonvulsant and antiepileptogenic effects of GABAA receptor ligands in
      pentylenetetrazole-kindled mice.
AB  - Although animal models based on pentylenetetrazole (PTZ) are widely used, the
      mechanism by which PTZ elicits its action is not very well understood. At the
      molecular level, a generally accepted mechanism of PTZ is noncompetitive
      antagonism of the gamma-aminobutyric acid (GABA)(A) receptor complex. By a
      systematic pharmacological investigation of various GABA(A) receptor ligands, our
      aim was to gain a better understanding of the GABAergic mechanisms involved in
      different PTZ-induced seizures. We investigated anticonvulsant effects of various
      specific GABA(A) receptor ligands, which are believed to bind to different
      binding sites on the GABA(A) receptor complex, on PTZ-induced clonic seizures in
      drug naive and PTZ-kindled mice as well as their effects on the development of
      PTZ kindling. Diazepam and alphaxalone produced potent anticonvulsant effects and
      completely suppressed the development of kindling. In contrast, the antagonists
      bicuculline and dehydroepiandrosterone sulfate (DHEAS) displayed neither
      anticonvulsant nor antiepileptogenic effects. Flumazenil, often used as a
      reference antagonist at the GABA(A) receptor benzodiazepine (BZ) binding site,
      lacked anticonvulsant effects but surprisingly inhibited the development of PTZ
      kindled seizures. The agonist 4,5,6,7-tetrahydroisoxazolo-(5,4-c)pyridin-3-ol
      (THIP) was devoid of both anticonvulsant and antiepileptogenic effects. Marked
      differences in drug sensitivity were observed between models based on single and
      chronic administration of PTZ showing that the two sets of models are
      fundamentally different. These results describe the pharmacology of a set of
      ligands believed to bind to different sites at the GABA(A) receptor complex in
      animal models based on PTZ and demonstrate that a drug's action in these models
      cannot be readily explained by agonistic or antagonistic properties at the
      receptor level.

PMID- 14687865
TI  - Sex difference in psychological behavior changes induced by long-term social
      isolation in mice.
AB  - Social isolation can induce psychological behavior changes. It is interesting to
      know whether there is sex difference in responding to social isolation or not.
      The present study compared the behavior difference between male and female mice
      isolated for 1-4 months. The results showed that the isolated male mice had
      higher accounts of locomotor activity than the isolated female and group-housed
      ones. Both isolated male and female mice spent shorter time in the dark box than
      the group-housed mice in the light/dark test, and isolated male mice spent less
      time in the closed arms than isolated female and group-housed mice when isolated
      for 2, 3 and 4 months in the elevated plus-maze test. These results suggest that
      isolation induce an anxiolytic-like effect. The immobile time in the forced
      swimming test was shortened in male mice isolated for 1 and 2 months. Both
      isolated male and female mice showed shorter time in pentobarbital-induced loss
      of righting reflex and less body weight gain. These results demonstrated that
      there was a sex difference in psychological behavior changes in mice undergoing
      social isolation and the male mice were more easily affected by isolation.

PMID- 14687866
TI  - Impaired memory following predatory stress in mice is improved by fluoxetine.
AB  - The first purpose of the present study was to investigate possible effects of
      predatory stress (i.e., 5-min cat exposure) on short-term learning abilities in
      Swiss mice using the object recognition test (ORT). The second aim was to
      evaluate the effects of anxiolytics (i.e., diazepam and fluoxetine) on
      learning/memory abilities in the ORT following predatory stress. Results showed
      that predatory exposure impaired learning and produced amnesia of acquired
      information or impairment to retrieve learned information (48 and 96 h
      poststressor). The learning impairment in the ORT in stressed mice was restored
      by acute fluoxetine treatment, but not by diazepam that instead affected learning
      in nonstressed animals. Taken together, these findings indicate that this animal
      model of exposure of mice to unavoidable predatory stimuli produces early
      cognitive changes analogous to those seen in patients with acute stress disorder
      (ASD).

PMID- 14687867
TI  - Aggressive responding in abstinent heroin addicts: neuroendocrine and personality
      correlates.
AB  - Objective measures of experimentally induced aggressiveness were evaluated in 20
      abstinent heroin-dependent subjects, in comparison with 20 normal healthy male
      subjects. All the subjects were preliminarily submitted to DSM-IV interviews,
      Buss-Durkee Hostility Inventory (BDHI) and Minnesota Multiphasic Personality
      Inventory (MMPI II). During a laboratory task, the Point Subtraction Aggression
      Paradigm (PSAP), subjects earned monetary reinforcers with repeated button
      presses and were provoked by the subtraction of money, which was attributed to a
      fictitious other participant. Subjects could respond by ostensibly subtracting
      money from the fictitious subject (the aggressive response). Money-earning
      responses were not different in drug-free heroin addicts and controls during the
      first two sessions and significantly lower during the third session in heroin
      dependent subjects (t=2.99, P<.01). Aggressive responses were significantly
      higher (F=4.9, P<.01) in heroin addicted individuals, in comparison with
      controls. During the experimentally induced aggressiveness, plasma
      adrenocorticotropic hormone (ACTH) and cortisol (CORT) concentrations increased
      less significantly, and norepinephrine (NE) and epinephrine (EPI) levels,
      together with heart rate (HR), increased more significantly in abstinent heroin
      dependent subjects than in healthy subjects. PSAP aggressive responses positively
      correlated with catecholamine changes, BDHI "direct" and "irritability" scores,
      MMPI "psychopathic deviate" scores in heroin-dependent subjects and controls, and
      with CORT responses only in healthy subjects. No correlation was found between
      heroin-exposure extent (substance abuse history duration) and aggressiveness
      levels. The present findings suggest that heroin-dependent patients have higher
      outward-directed aggressiveness than healthy subjects, in relation with monoamine
      hyperreactivity, after long-term opiate discontinuation. Aggressiveness in heroin
      addicts seems to be related more to the personality traits than to drug effects.
      The impairment of hypothalamus-pituitary-adrenal (HPA) axis in abstinent addicted
      individuals could be due to a long-lasting action exerted by opiates on
      proopiomelanocortin (POMC) or to a premorbid psychobiological condition, in
      association with increased sympathetic arousal.

PMID- 14687868
TI  - The serotonin-dopamine interaction is critical for fast-onset action of
      antidepressant treatment: in vivo studies in an animal model of depression.
AB  - In the last decade, many new antidepressants have been developed that display a
      more rapid onset to clinical effects than classical antidepressants. However, the
      mechanism that enables some drugs to have a faster onset of action than others is
      poorly understood. The aim of the present study was to determine neural
      alterations that are specific to fast-acting antidepressant action using Flinders
      Sensitive Line (FSL) rats, an animal model of depression. Because of the central
      role of accumbal dopamine in the mediation of motivation and reward, our
      measurements were focused on dopaminergic neurotransmission in the nucleus
      accumbens (NAC). The authors found that 7-day treatment with nefazodone (a
      putative fast-onset antidepressant) but not with desipramine (a classical
      antidepressant) normalized immobility time in the swim test in FSL rats.
      Serotonin (5-HT)-induced dopamine release but not basal dopamine levels
      correlated with the improvement of depressive-like behavior. The authors conclude
      that the 5-HT-dopamine interaction is critical to the fast-onset action of
      antidepressant treatment.

PMID- 14687869
TI  - The modulation of cocaine-induced conditioned place preferences by alcohol:
      effects of cocaine dose.
AB  - Busse and Riley [Biol. Psychiatry 26 (2002) 1373] have recently reported that
      alcohol dose dependently attenuated cocaine-induced place preferences. Although
      the mechanism for this effect is not known, it is possible that it is due to
      alcohol potentiating the aversive properties of cocaine, a potentiation that
      masks or abates cocaine's rewarding effects in this preparation. Given that the
      affective properties of cocaine (both aversive and rewarding) have been reported
      to be dose dependent, it might be expected that alcohol's ability to affect
      cocaine-induced place preferences would be influenced by changes in cocaine dose.
      To address this possibility, the following experiments assessed the effects of
      alcohol (0.5 g/kg) on place preferences induced by high (20, 30 and 40 mg/kg:
      Experiment 1) and low (2.5 and 5 mg/kg; Experiment 2) doses of cocaine.
      Specifically, every other day for four cycles male Sprague-Dawley rats were
      injected with cocaine, alcohol or one of several cocaine/alcohol combinations
      immediately before being placed on one side of a two-compartment place preference
      chamber. On alternate days, they were placed on the other side of the chamber
      after being injected with the drug vehicle(s). In Experiment 1, all doses of
      cocaine (20, 30 and 40 mg/kg) produced a significant preference for the drug
      paired compartment, whereas alcohol alone produced no effect. When given in
      combination, alcohol attenuated the cocaine-induced place preference (at 30 and
      40 mg/kg cocaine). In Experiment 2, neither cocaine (2.5 or 5 mg/kg) nor alcohol
      produced a significant effect when given alone. However, animals receiving the
      combination of alcohol and cocaine (5 mg/kg) displayed a significant place
      preference. These findings indicate that alcohol can both weaken and strengthen
      cocaine-induced place preferences, possibly via its effects on the rewarding and
      aversive properties of cocaine. The effect of alcohol is dependent on the dose of
      cocaine.

PMID- 14687870
TI  - Clozapine and cocaine effects on dopamine and serotonin release in nucleus
      accumbens during psychostimulant behavior and withdrawal.
AB  - There is an increasing awareness that a psychosis, similar to that of
      schizophrenic psychosis, can be derived from cocaine addiction. Thus, the
      prototypical atypical antipsychotic medication, clozapine, a 5-HT(2)/DA(2)
      antagonist, was studied for its effects on cocaine-induced dopamine (DA) and
      serotonin (5-HT) release in nucleus accumbens (NAcc) of behaving male Sprague
      Dawley laboratory rats with In Vivo Microvoltammetry, while animals' locomotor
      (forward ambulations), an A(10) behavior, was monitored at the same time with
      infrared photobeams. Release mechanisms for monoamines were determined by using a
      depolarization blocker, gamma-butyrolactone (gammaBL). BRODERICK PROBE
      microelectrodes selectively detected release of DA and 5-HT within seconds and
      sequentially in A(10) nerve terminals, NAcc. Acute and subacute studies were
      performed for each treatment group. Acute studies are defined as single injection
      of drug(s) after a stable baseline of each monoamine and locomotor behavior has
      been achieved. Subacute studies are defined as 24-h follow-up studies on each
      monoamine and locomotor behavior, in the same animal at which time, no further
      drug was administered. Results showed that (1) acute administration of cocaine
      (10 mg/kg ip) (n=5) significantly increased both DA and 5-HT release above
      baseline (P<.001) while locomotion was also significantly increased above
      baseline (P<.001). In subacute studies, DA release decreased significantly below
      baseline (P<.001) and significant decreases in 5-HT release occurred at the 15
      min mark and at each time point during the second part of the hour (P<.05); the
      maximum decrease in 5-HT was 40% below baseline. Locomotor behavior, on the other
      hand, increased significantly above baseline (P<.05). (2) Acute administration of
      clozapine/cocaine (20 and 10 mg/kg ip, respectively; n=6) produced a significant
      block of the cocaine-induced increase in DA (P<.001) and 5-HT release (P<.001).
      Cocaine-induced locomotion was blocked simultaneously with each monoamine by
      clozapine as well (P<.001). In subacute studies, DA release continued to be
      blocked presumably via clozapine by exhibiting a statistically significant
      decrease (P<.001), but 5-HT release increased significantly (P<.001), while
      cocaine-induced locomotor activity also continued to be antagonized by clozapine,
      i.e., locomotor activity exhibited no difference from baseline (P>.05). In
      summary, acute studies (a) support previous data from this laboratory and others
      that cocaine acts as a stimulant on the monoamines, DA and 5-HT and on locomotor
      behavior as well and (b) show that clozapine, 5-HT(2)/DA(2) antagonist, blocked
      enhanced DA, 5-HT and psychomotor stimulant behavior induced by cocaine. Subacute
      studies (a) suggest that withdrawal responses occurred in the cocaine group,
      based on recorded deficiencies in monoamine neurotransmitters (b) show that
      withdrawal effects in the cocaine group likely presynaptic, were distinguished
      from locomotor behavior, classically known to be mediated postsynaptically, and
      finally, (c) suggest that clozapine, with longer lived pharmacokinetic
      properties, reversed 5-HT cocaine-related withdrawal effects, but was unable to
      reverse DA cocaine-related withdrawal responses. Taken together with data from
      this laboratory, in which the 5-HT(2A/2C) antagonist, ketanserin, affected
      cocaine neurochemistry in much the same way as did clozapine, a mediation by
      either separate or combined 5-HT(2A/2C) receptors for these clozapine/cocaine
      interactions, is suggested. Further studies, designed to tease out the responses
      of selective 5-HT(2A) and 5-HT(2C) receptor compounds to cocaine and
      clozapine/cocaine, are underway.

PMID- 14687871
TI  - Olanzapine versus clozapine in treatment-resistant or treatment-intolerant
      schizophrenia.
AB  - Clozapine has been the gold standard for treatment of patients with refractory
      schizophrenia but is associated with serious safety liabilities. This has
      prompted the search for therapeutic alternatives for treatment-resistant
      schizophrenia. The objective of this study was to compare the efficacy and safety
      of olanzapine versus clozapine in schizophrenic patients who failed to respond
      adequately to antipsychotic medication or who experienced intolerable adverse
      effects associated with the medication. This 18-week, randomized, double-blind,
      parallel study compared treatment with either olanzapine (5-25 mg/day, n=75) or
      clozapine (100-500 mg/day, n=72) in patients with schizophrenia who were
      nonresponsive to, or intolerant of, standard acceptable antipsychotic therapy. At
      the 18-week endpoint, no statistically significant differences were found between
      olanzapine and clozapine in any efficacy measure used: Positive and Negative
      Syndrome Scale (PANSS) total, positive, negative, or general psychopathology or
      Clinical Global Impression severity (CGI-S). Response rates based on the criteria
      of Kane et al. [Arch. Gen. Psychiatry 45 (1988) 789] were also not significantly
      different between olanzapine-treated (57.9%) and clozapine-treated patients
      (60.8%). There were no significant differences in measurements of extrapyramidal
      symptoms or electrocardiography, and no clinically and statistically significant
      changes were seen in vital signs or laboratory measures in either group. Both
      treatments were well tolerated. Olanzapine demonstrated similar efficacy to
      clozapine in patients who had failed previous treatment because of lack of
      efficacy (treatment resistance) or intolerable side effects (treatment
      intolerance). Olanzapine therefore presents a safe alternative in the treatment
      of refractory schizophrenia.

PMID- 14687872
TI  - Double-blind, placebo-controlled study of zinc sulfate in the treatment of
      attention deficit hyperactivity disorder.
AB  - BACKGROUND: The most commonly used medications for attention deficit
      hyperactivity disorder (ADHD) are the psychostimulants. There is, however,
      considerable awareness in alternative, nonstimulant therapies, because some
      patients respond poorly to stimulants or are unable to tolerate them. Some
      studies suggest that deficiency of zinc play a substantial role in the
      aetiopathogenesis of ADHD. Therefore, to assess the efficacy of zinc sulfate we
      conducted treatment trial. METHODS: Patients with a primary DSM-IV diagnosis of
      ADHD (N=400; 72 girls, 328 boys, mean age=9.61+/-1.7) were randomly assigned in a
      1:1 ratio to 12 weeks of double-blind treatment with zinc sulfate (n=202) (150
      mg/day) or placebo (n=198). Efficacy was assessed with the Attention Deficit
      Hyperactivity Disorder Scale (ADHDS), Conners Teacher Questionnaire, and DuPaul
      Parent Ratings of ADHD. Primary efficacy variables were differences from baseline
      to endpoint (last observation carried forward) in mean ADHDS and Conners Teacher
      Questionnaire scores between the zinc sulfate and the placebo groups. Safety
      evaluations included monitoring of adverse events, vital signs and clinical
      laboratory values. RESULTS: Zinc sulfate was statistically superior to placebo in
      reducing both hyperactive, impulsive and impaired socialization symptoms, but not
      in reducing attention deficiency symptoms, as assessed by ADHDS. However, full
      therapeutic response rates of the zinc and placebo groups remained 28.7% and 20%,
      respectively. It was determined that the hyperactivity, impulsivity and
      socialization scores displayed significant decrease in patients of older age and
      high BMI score with low zinc and free fatty acids (FFA) levels. Zinc sulfate was
      well tolerated and associated with a low rate of side effect. CONCLUSIONS: Zinc
      monotherapy was significantly superior to placebo in reducing symptoms of
      hyperactivity, impulsivity and impaired socialization in patients with ADHD.
      Although by themselves, these findings may not be sufficient, it may well be
      considered that zinc treatment appears to be an efficacious treatment for ADHD
      patients having older age and high BMI score with low zinc and FFA levels.

PMID- 14687873
TI  - Digit length pattern in schizophrenia suggests disturbed prenatal hemispheric
      lateralization.
AB  - The differentiation of the human brain is triggered by sexual steroid hormones in
      the fetus. The development of both the urogenital system and the appendicular
      skeleton are under common control by the HOX genes. Generally men have longer
      ring fingers than index fingers, whereas in women these fingers are close to
      equal. The inborn digit pattern may reflect fetal estrogen/androgen influences on
      hemispheric brain specialization. Reduced hemispheric asymmetry has been found in
      schizophrenia. Gender differences in schizophrenia also suggest a possible
      endocrine component in the complex pathogenesis of the illness. To test this
      hypothesis the authors have measured the relative digit lengths of patients with
      schizophrenia and healthy comparison subjects. The distance of the tip of the
      index and ring finger was measured from the tip of the third digit in 80 male and
      80 female, right-handed patients with DSM-IV diagnosis of schizophrenia and in 80
      right-handed healthy comparison men and women. Schizophrenic men and women showed
      a more "feminine" phenotype of the index and ring fingers in both hands than same
      sex controls. This finding implies that low fetal androgen/estrogen ratio may
      have a predisposing role in the development of schizophrenia and points toward
      involvement of endocrine factors in the disturbed hemispheric lateralization
      attributed to the illness.

PMID- 14687874
TI  - Asterixis and toxic encephalopathy induced by gabapentin.
AB  - PURPOSE: To date, only one case of asterixis associated with the use of
      gabapentin (GBT) has been reported. No data, instead, are available on the
      occurrence of asterixis related to a dementing encephalopathy during GBT therapy
      in the elderly. METHODS: Case reports of two elderly patients, one with
      asterixis, the other with asterixis and encephalopathy, associated with the use
      of GBT, as adjunctive therapy, at dosages of 900 to 3600 mg/day are given. In one
      patient, GBT was added to oxcarbazepine (OXCBZ). FINDINGS: Both patients
      experienced resolution of the clinically apparent asterixis, and of the toxic
      encephalopathy, on discontinuation or reduction of GBT dosages. One patient
      developed asterixis after drug rechallenge. In the patient on OXCBZ, the analysis
      of the electromyogram (EMG) activity showed the occurrence of a subclinical
      asterixis. CONCLUSIONS: Our study indicates that high doses of GBT may induce
      asterixis related to a reversible encephalopathy. Low doses of GBT, instead, may
      induce a disabling asterixis when given in combination with OXCBZ because of a
      synergistic interaction between these drugs.

PMID- 14687875
TI  - Lithium intoxication, hypercalcemia and "accidentally" induced food and water
      aversion: a case report.
AB  - Lithium is widely used in the management of patients with affective and other
      behavioral disorders. In addition to its therapeutic role, it is important to
      recognize that it occasionally causes severe side effects. Associated with its
      long-term use, parathyroid hypersecretion and hypercalcemia is a rare but
      reported side effect. A 54-year-old patient is reported who previously had a good
      response to lithium carbonate treatment of his bipolar disorder. Suddenly, and
      after 15 years of lithium carbonate use, he presented food and water aversion,
      hypercalcemia, lithium intoxication (SLi of 4.30 mmol/l) and acute renal
      insufficiency. Haemodialysis was carried out and the patient improved
      dramatically.

PMID- 14687876
TI  - What causes seasonality of birth in schizophrenia?
AB  - An excess of winter-spring births (and/or a decrease of summer births) has
      consistently been observed in schizophrenia (SCZ). This observation may provide a
      significant clue about the causes of the disease if specific factors which cause
      the phenomenon can be determined. This paper reviews several studies which
      investigated factors correlated with this observation in SCZ, in an attempt to
      determine which factors more likely cause the seasonality. Among the candidates
      of the factors are meteorological variables (such as ambient temperature),
      several infections, maternal hormones, sperm quality, nutrition and external
      toxins. A variation of procreation might also have an effect. Among the factors,
      the most extensively studied are temperature and viral infections. Some of them
      have appeared promising, but further studies are definitely required. Several
      challenges, including complicated correlations of the factors and determination
      of the susceptible period during pregnancy, need to be overcome. Comparisons of
      the data from areas and cohorts with different patterns of the candidate factors
      may be helpful. Animal studies may also help investigate the molecular and
      physiological mechanisms of the phenomenon.

PMID- 14687877
TI  - Role of lactate in the brain energy metabolism: revealed by Bioradiography.
AB  - To elucidate the role of lactate in the brain, we used a novel method,
      'Bioradiography', in which the dynamic process could be followed in living slices
      by use of positron-emitter-labeled compounds and imaging plates. We studied the
      incorporation of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) into rat brain slices
      incubated in oxygenated Krebs-Ringer solution. Under the glucose-free condition,
      [18F]FDG uptake rate in the cerebral cortex decreased with time and plateaued
      within 350 min but the addition of 5 mM lactate made the [18F]FDG uptake linear.
      When an inhibitor of the lactate transporter, 0.5 mM alpha-cyano-4
      hydroxycinnamate (4-CIN) was applied to the glucose-free solution, the uptake
      rate decreased. Under the normal glucose condition, [18F]FDG uptake linearly
      increased for 6 h, but when 10 mM lactate was applied, the uptake rate decreased.
      In contrast, when 0.5 mM 4-CIN was applied to the normal glucose solution,
      [18F]FDG uptake rate increased. These results suggest that exogenous and
      endogenous lactate can substitute for glucose in the brain.

PMID- 14687878
TI  - Synaptology of the rostral reticular thalamic nucleus of absence epileptic
      WAG/Rij rats.
AB  - The adult WAG/Rij rat is a well-established animal model for human absence
      epilepsy characterized by the presence of spike-wave discharges (SWDs). The
      pacemaking activity of the rostral reticular thalamic nucleus (rRTN) has been
      demonstrated to be essential for SWD maintenance. We investigated if SWD
      maintenance can be related to the synaptic organization of the rRTN, by studying
      the ultrastructure of the rRTN of absence epileptic WAG/Rij rats in comparison
      with that of non-epileptic, age-matched ACI control rats. In WAG/Rij rats, D-, L-
      and F-type terminals constitute the synaptic organization of the rRTN. D-type
      synapses, especially axo-dendritic ones, occur frequently. L- and F-type
      terminals are common but less frequent than D-type terminals. Semi-quantitative
      observations indicate that all terminal types are present on different parts of
      the postsynaptic neuron, but in different numbers: they are frequent on
      dendrites, common on somata and axons, and occur occasionally on dendritic
      spines. In addition, occasionally an F-type terminal was observed on the axon
      hillock. The three terminal types are also involved in multiple synaptic
      configurations, convergent as well as divergent, with dendrites, somata, axon
      hillocks and axons as postsynaptic structures. Convergent synaptic configurations
      outnumber divergent ones. The synaptic organization of the rRTN of the non
      epileptic ACI rat appears to be very similar to that of the epileptic WAG/Rij
      rat. This indicates that SWD maintenance in the WAG/Rij rat does not depend on a
      different synaptic organization of the rRTN.

PMID- 14687879
TI  - The small GTP-binding protein RhoA regulates serotonin-induced Na+-current
      response in the neurons of Aplysia.
AB  - Application of serotonin (5-HT) induces a slow inward current response in
      identified neurons of Aplysia ganglia under voltage clamp. The 5-HT-induced
      current response was depressed in Na+-free media, but augmented in Ca2+-free
      media, and unaffected by a change in external K+. The 5-HT-induced response was
      markedly blocked by intracellular injection of guanosine 5'-O-(2-thiodiphosphate)
      (GDPbetaS). After the injection of guanosine 5'-O-(3-thiotriphosphate)
      (GTPgammaS), the responses to 5-HT gradually and significantly increased at the
      initial period, reached its plateau, and finally decreased. Intracellular
      injection of Clostridium difficile toxin B, a blocker of small G-protein Rho
      family members such as Rho (RhoA, RhoB and RhoC), Rac and Cdc42, markedly
      depressed the 5-HT-induced response. Intracellular injection of Clostridium
      botulinum C3 exoenzyme, a specific blocker of RhoA, RhoB, RhoC, exhibited a
      similar depressing effect observed with toxin B. In contrast, intracellular
      injection of recombinant L63RhoA, a constitutively active form of RhoA,
      significantly augmented the 5-HT-induced response without affecting the resting
      membrane. These results suggested that the 5-HT-induced Na+-current response
      might be facilitated by the activation of Aplysia Rho which is closely homologous
      to RhoA, RhoB or RhoC in mammalian neuron.

PMID- 14687880
TI  - Input-output organization of the rostral part of the dorsal premotor cortex, with
      special reference to its corticostriatal projection.
AB  - Until recently, little was known about the rostral part of the dorsal premotor
      cortex (PMdr). In the present study, somatotopical representations of the PMdr
      were electrophysiologically identified in the macaque monkey, and the
      distribution of corticostriatal input from the forelimb region of the PMdr was
      analyzed in relation to its thalamocortical and intracortical (with the frontal
      lobe) connections. Results have revealed that (1) the forelimb is represented
      predominantly in the PMdr, while only a few sites representing other body parts
      are distributed as embedded within the forelimb representation; (2) the
      corticostriatal input zone is located in the striatal cell bridges and their
      surroundings; (3) the cells of origin of the thalamocortical projections to the
      PMdr are located mainly in the parvicellular division of the ventroanterior
      nucleus, the oral divison of the ventrolateral nucleus, area X, the caudal
      divison of the ventrolateral nucleus, the mediodorsal nucleus, and the
      intralaminar nuclear group; (4) the PMdr is interconnected primarily with higher
      order motor-related areas and dorsal area 46. These data indicate that the input
      output pattern of the PMdr resembles those of the presupplementary motor area and
      the rostral cingulate motor area, and that the PMdr may play critical roles in
      higher-order motor functions.

PMID- 14687881
TI  - Effects of corollary discharge on event-related potentials during selective
      attention task in healthy men and women.
AB  - Corollary discharge is a brain electrical activity associated with self
      monitoring, which distinguishes self from others in thoughts or behaviors.
      Corollary discharge can be non-invasively assessed using event-related potential
      (ERP) recordings in humans. Previous studies have revealed that the amplitude of
      the N100 component elicited during an "odd-ball" task is reduced while a healthy
      subject is vocalizing, which may index the effect of corollary discharge on
      auditory ERPs. In this study, we attempted to assess the effect of vocalization
      on ERP components including N100, mismatch negativity (MMN), negative difference
      wave (Nd), and P300 during a selective attention task in 22 healthy adults. We
      also evaluated the possible contribution of gender to these effects. N100
      amplitudes elicited by unattended standard stimuli were reduced under the
      vocalization condition compared with those under the baseline condition. However,
      there were no significant effects of vocalization on MMN, Nd or P300. Moreover,
      there was no significant effect of gender to the corollary discharge. These
      results suggest that the effect of corollary discharge on auditory ERPs is
      limited to the perceptual stage of information processing in healthy men and
      women.

PMID- 14687882
TI  - In vivo labeling of amyloid with BF-108.
AB  - Detection of aggregated amyloid-beta (Abeta) with a non-invasive imaging modality
      such as positron emission tomography (PET) was suggested to be ideal for the
      diagnosis of Alzheimer's disease (AD) prior to the onset of clinical symptoms. We
      have been searching for imaging probe candidates with a high affinity for
      aggregated Abeta in vitro and in vivo and high lipophilicity, a characteristic
      that allows for the permeation of the blood-brain barrier (BBB). As analyzed by
      Thioflavin T (ThT) assay and octanol/water partition coefficient test (PC), 3
      diethylamino-6-(2-fluoroethyl)ethylaminoacridine (BF-108) were found to have high
      affinity for Abeta aggregates in vitro and high lipophilicity. Intravenously
      administrated BF-108 labeled Abeta aggregates injected into the amygdala as
      observed under a fluorescence microscope, showing this compound's permeability of
      BBB and an ability to label Abeta in vivo. BF-108 also labeled neuritic senile
      plaques (SPs), neurofibrillary tangles, and amyloid-laden vessels in temporal and
      hippocampal sections from AD patients. Following intravenous administration of BF
      108 to an APP23 transgenic (TG) mouse, in vivo labeling of endogenous plaques was
      seen in brain sections by fluorescence microscopy. These properties suggest the
      potential utility of BF-108 for in vivo imaging of AD pathology.

PMID- 14687883
TI  - Proteinase K enhanced immunoreactivity of the prion protein-specific monoclonal
      antibody 2A11.
AB  - Here, we report the development and further characterisation of a novel PrP
      specific monoclonal antibody: 2A11. By Western blot analysis, 2A11 reacts with
      PrPC from a variety of species including cow, sheep, pig, hamster, rabbit, cat,
      dog, deer and mouse but fails to react with human, chicken and turtle PrP.
      Reactivity to PrPC in Western blot was found to be dependent on the redox state
      of the protein since binding of mAb 2A11 to its epitope was more effective in
      reducing conditions. 2A11 binding site was mapped within a region comprised by
      residues 171-179 (six octarepeats bovine PrP notation; 163-171 for the ovine PrP
      notation). Interestingly, in immunohistochemistry (IHC) analysis,
      immunoreactivity was greatly enhanced after proteinase K (PK) sample treatment,
      while little or no reaction was observed in non-PK-treated BSE samples and
      samples from healthy animals. Quantitative differences in reactivity to BSE
      prions after PK treatment were also observed, to a lesser extent, by Western blot
      analysis. Since definitive diagnosis of prion diseases rely on IHC assays of
      proteinase K-treated samples, the use of mAb 2A11 might contribute to reduce the
      occurrence of false positive detection due to incomplete proteinase K digestion.

PMID- 14687884
TI  - NMDA receptor-mediated immediate Ser831 phosphorylation of GluR1 through
      CaMKIIalpha in rat hippocampus during early global ischemia.
AB  - The phosphorylation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      (AMPA) receptors subunit GluR1 at Ser831 has been implicated in the regulation of
      AMPA receptors channel. In this paper, Ser831 phosphorylation of GluR1 in rat
      hippocampus was investigated, which significantly increased during early global
      ischemia. To further illustrate the underlying mechanisms, calcium/calmodulin
      dependent kinase IIalpha (CaMKIIalpha) inhibitor 1-[N,O-bis-(5
      isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN62), CaM
      antagonist trifluoperazine (TFP), N-methyl-D-aspartate (NMDA) receptor antagonist
      dextromethorphan (DEX), AMPA receptor antagonist 6,7-dinitro-quinoxaline-2,3
      (1H,4H)-dione (DNQX) and L-type voltage-gated Ca2+ channel (L-VGCC) blocker
      nifedipine (NIF), were respectively administrated to the rats 20 min prior to
      ischemia. The results showed that KN62, TFP and DEX significantly attenuated
      Ser831 phosphorylation of GluR1, while DNQX and NIF had no obvious effects.
      Consequently, the studies suggest that early global ischemia induced Ser831
      phosphorylation of GluR1 may be closely associated with CaMKIIalpha and the NMDA
      receptor, while the immediate Ser831 phosphorylation of GluR1 may have been
      involved in pathogenic events after early global ischemia.

PMID- 14687885
TI  - Contribution of changes in ubiquitin and myelin basic protein to age-related
      cognitive decline.
AB  - The structural substrates for age-associated cognitive and motor slowing are not
      known, but age-related white matter changes, such as ubiquitin (UBQ)
      immunoreactive granular degeneration of myelin, might contribute to this slowing.
      To address this hypothesis we measured immunoreactivity for UBQ and myelin basic
      protein (MBP) in frontal white matter of age-, sex- and postmortem interval
      matched cases with no cognitive impairment (NCI; N=12), mild cognitive impairment
      (MCI; N=14) and Alzheimer disease (AD; N=12). There were no significant
      correlations between UBQ in white matter and cognitive measures, but MBP was
      significantly lower in AD compared with NCI and MCI. MBP correlated with overall
      cognition as assessed by neuropsychological summary scores, as well as with timed
      cognitive tests and those that reflect frontal functions. An age-related decrease
      in MBP immunoreactivity was detected in NCI cases (r=0.71). These results support
      the hypothesis that white matter pathology may contribute to age-associated
      decline in cognition.

PMID- 14687886
TI  - Regulation of dendrite formation of Purkinje cells by serotonin through
      serotonin1A and serotonin2A receptors in culture.
AB  - Serotonergic fibers and receptors appear in the rat cerebellum during early
      postnatal development. In the present study, we investigated the actions of
      serotonin (5-HT) and its receptors in the dendrite formation of Purkinje cells in
      organotypic cultures of anterior and posterior lobes of the cerebellum at
      postnatal day 7. In anterior lobes after 4 days in vitro (4DIV), the dendritic
      areas and branchings of Purkinje cells were increased by the treatment of 2
      microM 5-HT, but decreased by 20 microM 5-HT. In posterior lobes after 4DIV, the
      dendritic areas of Purkinje cells were increased by 5-HT (2, 20 and 200 microM).
      In contrast, 5-HT treatment decreased dendritic areas of Purkinje cells in both
      anterior and posterior lobes after 7DIV. Next, we determined the actions of
      specific 5-HT receptors in mediating the effects of 5-HT by treatment with
      selective 5-HT receptor agonists. In anterior lobes after 4DIV, dendritic areas
      of Purkinje cells were increased by a 5-HT1A receptor agonist (8-OH-DPAT),
      whereas decreased by a 5-HT2A receptor agonist (DOI). The present study suggested
      that the dendrite formation of Purkinje cells is promoted by 5-HT through 5-HT1A
      receptors, but inhibited by 5-HT through 5-HT2A receptors.

PMID- 14687887
TI  - Temporal structure of the apparent motion perception: a magnetoencephalographic
      study.
AB  - Humans perceive motion when numerous small dots pattern is followed by one of the
      same pattern but with all the dots shifted a little in one direction. When the
      amount of shift exceeds a level humans no more perceive motion even though
      physical visual information does not change. Using this stimulus, we addressed to
      elucidate the temporal structure of the neural activity related to this apparent
      motion perception. The magnetic responses to the random-dot patterns with various
      amounts of shift were measured while the subjects were performing a direction
      discrimination task. A significant magnetic response amplitude change occurred
      with three distinct peaks when the response inducing apparent motion was compared
      with those inducing no motion without change in the response latencies. The major
      difference occurred at about 110, 140, 210 ms after the stimulus onset. The
      response origin was always within the occipitotemporal area. The results indicate
      that the neural activity for the perception of apparent motion can be measured by
      MEG that occur at least 110 ms after the stimulus onset possibly in the human
      MT+. Three distinct peaks in the response difference may represent the sequential
      multiple neural process proposed theoretically though further study is necessary
      to prove.

PMID- 14687888
TI  - Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer,
      atherosclerosis and diabetics.
AB  - Reactive oxygen species (ROS) produced either endogenously or exogenously can
      attack lipid, protein and nucleic acid simultaneously in the living cells. In
      nuclear and mitochondrial DNA, 8-hydroxydeoxyguanosine (8-OHdG), an oxidized
      nucleoside of DNA, is the most frequently detected and studied DNA lesion. Upon
      DNA repair, 8-OHdG is excreted in the urine. Numerous evidences have indicated
      that urinary 8-OHdG not only is a biomarker of generalized, cellular oxidative
      stress but might also be a risk factor for cancer, atherosclerosis and diabetes.
      For example, elevated level of urinary 8-OHdG has been detected in patients with
      various cancers. In human atherosclerotic plaques, there were increased amounts
      of oxidatively modified DNA and 8-OHdG. Elevated urinary 8-OHdG and leukocyte DNA
      were also detected in diabetic patients with hyperglycemia, and the level of
      urinary 8-OHdG in diabetes correlated with the severity of diabetic nephropathy
      and retinopathy. We have discussed various methods for determining 8-OHdG in the
      tissue and urine, including HPLC with and without extraction, and ELISA. Using
      the ELISA we developed, we found that the normal range of urinary 8-OHdG for
      females was 43.9 +/- 42.1 ng/mg creatinine and 29.6 +/- 24.5 ng/mg creatinine for
      males, respectively. We found that the normal value between females and males is
      significantly different (p < 0.001).

PMID- 14687889
TI  - Vitamins in human arteriosclerosis with emphasis on vitamin C and vitamin E.
AB  - INTRODUCTION: This review focuses on the process of arteriosclerosis arising from
      oxidative stress on lipoproteins and the general failure of randomized human
      trials using vitamins to retard this process. REVIEW: As well as clinical trials,
      the paper reviews the mechanisms by which a variety of oxidants act. Antioxidants
      are discussed, emphasizing interactions of vitamins C and E with transition
      metals that can lead to prooxidation. There is a focus on interactions between
      supplemental or co-antioxidants that counterbalance prooxidant effects of one
      another. CONCLUSIONS: It is concluded that normal cellular supplementation
      mechanisms are poorly accessible in the arteriosclerotic plaque leading to a
      prooxidant environment in which the haphazard introduction of vitamins could
      potentially be hazardous. Continued investigations into basic and clinical redox
      interactions of the kind discussed in this review using new measuring techniques
      may lead to approaches whereby antioxidants can be introduced into tissue in
      controlled ways for reducing arteriosclerosis.

PMID- 14687890
TI  - Evidence of oxidative stress in the circulation of ovarian cancer patients.
AB  - BACKGROUND: Ovarian cancer is the leading cause of death due to gynecological
      malignancies among women. The extent of free radical induced oxidative stress can
      be exacerbated by the decreased efficiency of antioxidant mechanisms. The present
      study was conducted to investigate the extent of oxidative stress and the levels
      of antioxidants in the circulation of ovarian cancer patients. METHODS: Plasma
      thiobarbituric acid reactive substances (TBARS) and conjugated dienes (CD) and
      the levels of antioxidants such as superoxide dismutase (SOD), catalase (CAT),
      vitamin C and vitamin E were estimated in the circulation of 30 ovarian cancer
      patients and an equal number of age-matched normal subjects as control. RESULTS:
      Significantly increased concentrations of plasma TBARS and CD and significantly
      lowered levels of SOD, CAT, vitamin C and vitamin E were observed in ovarian
      cancer patients as compared with normal subjects. CONCLUSION: The low levels of
      SOD, CAT, vitamin C and vitamin E in the plasma of ovarian cancer patients may be
      due to their increased utilization to scavenge lipid peroxides as well as their
      sequestration by tumor cells. Increased levels of lipid peroxidation may be due
      to excessive oxidative stress caused by incessant ovulation or epithelial
      inflammation.

PMID- 14687891
TI  - Protective role of alpha-tocopherol and caffeic acid phenethyl ester on ischemia
      reperfusion injury via nitric oxide and myeloperoxidase in rat kidneys.
AB  - BACKGROUND: The aim of this study was to determine the acute effects of
      antioxidant caffeic acid phenethyl ester (CAPE) and alpha-tocopherol (vitamin E)
      on nitric oxide (NO) production, neutrophil infiltration, and antioxidant enzyme
      activities on an in vivo model of renal ischemia-reperfusion injury. METHODS:
      Rats were divided into five equal groups each consisting six rats: sham
      operation, ischemia, ischemia-reperfusion (I/R), I/R plus CAPE, and I/R plus
      vitamin E groups. CAPE or vitamin E was administered intraperitoneally before
      reperfusion. After experimental procedure, rats were sacrificed and both
      ipsilateral and contralateral kidneys were removed and prepared for NO
      concentrations, myeloperoxidase (MPO), catalase (CAT) and superoxide dismutase
      (SOD) activities. RESULTS: Acute administration of vitamin E decreased NO
      concentrations in both ipsilateral and contralateral renal tissues compared to
      I/R group. SOD activity was increased in I/R and I/R + CAPE groups compared to
      sham operation group. The most prominent results were encountered in MPO
      activities, which did not change in contralateral kidneys in both ischemia and
      I/R groups. There was a significant decrease in ipsilateral MPO activity in
      ischemia group and a significant increase in I/R group compared to sham operation
      group. Pretreatment with intraperitoneal CAPE significantly diminished the tissue
      MPO activity indicating the prevention of the neutrophil sequestration into the
      kidney. CONCLUSION: There is a role for CAPE in attenuation in renal damage after
      I/R injury of the kidney, in part at least by inhibition of neutrophil
      sequestration.

PMID- 14687892
TI  - Urine 8-isoprostane F2alpha concentrations in patients with neurogenic bladder
      due to spinal cord injury.
AB  - BACKGROUND: Isoprostanes are prostaglandin-like end products of arachidonic acid
      peroxidation that are produced by a free radical-catalyzed mechanism. Considering
      its free radical-dependent formation and potent contractor effect, it is
      postulated that isoprostane 8-iso PGF2alpha may play an important role in
      oxidative stress-related smooth muscle dysfunction. These substances may also
      influence bladder activity directly by effects on the smooth muscle. The present
      study was designed to measure traditional biochemical parameters (MDA, TAS,
      vitamin E) in plasma and 8-iso PGF2alpha concentrations in urine of patients with
      spinal cord injury and to evaluate the relation of urinary isoprostane
      concentrations to the bladder function. METHODS: All spinal cord patients
      underwent urodynamic evaluations. The biochemical tests were performed in both
      hyperreflexic bladder group (n = 23) and areflexic bladder group (n = 10), and
      the findings were compared to those of the patients with normally functioning
      bladder (controls, n = 19). RESULTS: Urine 8-iso PGF2alpha concentrations were
      significantly increased in hyperreflexic group (median value 0.89 pg/mg
      creatinine) compared to both control (0.52 pg/mg creatinine) and areflexic groups
      (p < 0.001). The lowest concentrations of urinary 8-iso PGF2alpha were observed
      in the areflexic group (0.22 pg/mg creatinine), and these were positively
      correlated to the plasma MDA concentrations in areflexic patients (p = 0.05; r =
      0.684). CONCLUSION: Isoprostanes may be involved in the pathogenesis of
      neurogenic bladder dysfunction. It may be of value to determine the urinary
      concentrations of 8-iso PGF2alpha in order to distinguish areflexic bladders from
      the hyperreflectics.

PMID- 14687893
TI  - Development of a radiotransporter assay for determination of iodide: preliminary
      studies.
AB  - BACKGROUND: The principle of the radiotransporter assay (RATRA) is that the
      concentration of the substance to be assayed (analyte) is determined by the
      degree of its competitive inhibition of the binding of radioactive analyte with
      transporter. METHODS: To illustrate this approach, the iodide concentrations in
      urine samples were determined by means of RATRA using Na+/I- symporter (NIS).
      RESULTS: Iodide concentrations ranging from 9 x 10(-6) to 9 x 10(-4) mol/l could
      be measured without any significant interference of 0.85 mol/l NaCl. The mean
      recovery rate of added iodide to urine was 96.5%, serial dilutions of urine
      samples gave almost straight dose response lines passing near the zero point, the
      mean within assay coefficient of variation (CV) was 8.8% and between assay CV was
      12.9%. Although urinary iodide concentrations determined by RATRA correlated with
      those using a chemical method (r = 0.97) and an electrode method (r = 0.85),
      there were discrepancies in absolute values particularly at the low level among
      these. CONCLUSIONS: The RATRA may have a limitation with respect to the
      specificity for determining analytes in the biological materials, but we suggest
      it has the ability to detect some factors influencing the transport.

PMID- 14687894
TI  - Enzyme-linked immunosorbent assay for circulating human resistin: resistin
      concentrations in normal subjects and patients with type 2 diabetes.
AB  - BACKGROUND: Resistin is a recently identified adipocyte-secreted hormone in
      rodents, and has been proposed to serve as a link between obesity and insulin
      resistance. The aim of this study was to develop a sensitive enzyme-linked
      immunosorbent assay (ELISA) for human resistin and evaluate serum resistin
      concentrations in normal subjects and patients with type 2 diabetes. METHODS:
      Using ELISA developed by two polyclonal antibodies, resistin concentrations were
      measured in 90 patients with type 2 diabetes and compared to 74 healthy control
      subjects. RESULTS: This ELISA has high specificity and sensitivity over the
      concentration of range 0.5-100 ng/ml with good percentage recovery (97.1 +/-
      4.7%) and reproducibility (within-day assay, CV = 4.8-8.6%; between-day assay, CV
      = 5.6-9.7%). The mean concentration of resistin in sera from type 2 diabetic
      patients was significantly higher than that in normal subjects (mean +/- S.E.:
      20.8 +/- 0.7 vs. 14.9 +/- 0.5 ng/ml, p < 0.001). A moderate positive correlation
      was observed between serum resistin levels and body mass indices in both normal
      subjects (r = 0.412, p < 0.0003) and patients with type 2 diabetes (r = 0.395, p
      < 0.0001). CONCLUSIONS: Our ELISA will be useful to confirm the physiological and
      pathophysiological role of resistin in humans.

PMID- 14687895
TI  - Inhibitory effect of caffeic acid phenethyl ester on bleomycine-induced lung
      fibrosis in rats.
AB  - BACKGROUND: Pulmonary fibrosis (PF) induced by anticancerogenic bleomycin (BLM)
      is one of the more common side effects encountered during cancer treatment. It
      has been suggested in the last decades that the main responsible agent in PF is
      reactive oxygen species which were generated also in normal physiological
      conditions in the human body. In this experimental study, we investigated the
      preventive or attenuating effects of caffeic acid phenethyl ester (CAPE) that has
      been demonstrated to have anti-inflammatory, cytocytatic, anticancerogenic,
      antiprolipherative and antioxidant effects on BLM-induced PF. METHODS: Thirty-six
      Sprague-Dawley rats were divided randomly into four groups as sham operation,
      BLM, BLM + vitamin E (vit E), and BLM + CAPE groups. BLM (7.5 mg/kg, single dose)
      was applied intratracheally, and CAPE and vit E intraperitoneally in the
      appropriate groups. At the end of the fibrosis processes, lung tissues were
      removed and the levels of tissues hydroxyproline (OH-proline), malondialdehyde
      (MDA) and NO as well as the activities of superoxide dismutase (SOD), catalase
      (CAT) and myeloperoxidase (MPO) were determined. Also, the weights of the rats
      were recorded at 7th and 14th days of the experiments. RESULTS: BLM application
      to the rats resulted in a significant increase in the OH-proline level as
      compared to the controls. Administration of CAPE and vit E led to the remarkable
      reduction of total lung OH-proline levels compared to the rats treated with BLM
      alone (p < 0.0001). There were a decreases in antioxidant enzyme (SOD and CAT)
      activities while an increase in MPO activity in BLM group was found vs. the
      control group (p < 0.0001). CAPE had a regulator effect on these parameters: the
      increase in CAT and SOD activities and the decrease in MPO activity were seen
      after CAPE application. NO, MDA and OH-proline levels were increased in BLM group
      vs. the control group. CAPE was more effective in decreasing the tissue levels of
      NO, MDA and OH-proline than vit E. MPO activity, as a good marker of neutrophil
      sequestration to the tissues, in the BLM group was decreased by CAPE
      approximately to the control group. CONCLUSION: We suggest that CAPE is more
      effective on the prevention of BLM-induced fibrosis via antioxidant and free
      radical scavenger properties than vit E at the doses used in the present study.
      CAPE has some attenuating effects on BLM-induced PF affecting both oxidant and
      antioxidant systems as well as neutrophils sequestration.

PMID- 14687896
TI  - The clinical significance of gelatinase B in gouty arthritis of the knee.
AB  - BACKGROUND: Clinically, gouty arthritis is associated with severe inflammation,
      such as pain, swelling and erythema of the joints. Gelatinase A and B (matrix
      metalloproteinase-2 and -9, MMP-2 and -9) participate in the degradation of the
      extracellular matrix (ECM) components in a variety of arthritis, especially in
      the inflammatory arthritis. METHODS: We examined the levels of MMP-2 and -9 in 40
      synovial fluids (SFs) from the knee joints of 24 patients with gouty arthritis
      and compared them with the clinical and laboratory variables of inflammation.
      RESULTS: Gelatin zymography revealed that not only activated MMP-2 levels but
      also proMMP-9 levels in SF from the knee joints of gouty arthritis were
      associated with the local arthritis activity scores (LAS) (p < 0.001) and
      correlated well with the neutrophil counts in SF as well (p < 0.001). A similar
      correlation between proMMP-9 levels and LAS was also found within the individual
      patients before and during treatment with nonsteroidal antiinflammatory drugs
      (NSAIDs; p < 0.001). ProMMP-2 appeared in all SFs irrespective of LAS and
      neutrophil counts. CONCLUSIONS: The analysis of MMP-9 in SF samples can reveal
      the inflammatory condition of the knee joints with gouty arthritis. Joint
      aspiration may decrease the amount of MMPs in SF to attack the ECM of joint
      whether it is normal or not.

PMID- 14687897
TI  - Upregulation of CD40--CD40 ligand system in patients with diabetes mellitus.
AB  - BACKGROUND: Diabetes is associated with an increased risk of cardiovascular
      disease and atherosclerosis. Increasing evidence shows that CD40-CD40L
      interaction plays a crucial role in the pathogenesis of atherosclerosis and
      coronary artery disease. The purpose of this study was to assess whether CD40
      system expressions were disrupted in patients with diabetes. METHODS: Sixteen
      normal controls and 72 patients including 20 with type 2 diabetes mellitus (DM),
      15 with type 1 DM, 20 with coronary heart disease (CHD) and 17 CHD with
      coexisting DM were investigated. The expression of CD40 and CD40L on platelet was
      analyzed by indirect-immunofluorescence flow cytometry and serum-soluble CD40L
      level was determined by a commercially available ELISA. Serum of AGE was detected
      by fluorescence spectroscopy. RESULTS: Type 1 DM, type 2 DM, CHD and CHD Patients
      with coexisting diabetes showed a significant increase of CD40 (81.8 +/- 11.7,
      70.7 +/- 11.6, 68.5 +/- 10.2, 79.9 +/- 11.9 MIF, respectively) and CD40L (18.4 +/
      5.1, 13.9 +/- 4.1, 13.5 +/- 3.7, 16.7 +/- 4.7 MIF, respectively) coexpression on
      platelets as well as sCD40L (15.6 +/- 3.5, 14.1 +/- 3.3, 12.2 +/- 3.5, 13.5 +/-
      3.6 ng/ml, respectively) compared with controls (p < 0.01). A positive
      correlation was found between serum AGE levels in patients with DM and CD40-CD40L
      system. We also observed a significant correlation between hemoglobinA1c (HbA1c)
      concentration and CD40L on platelets (r = 0.71, p < 0.001) as well as sCD40L (r =
      0.69, p < 0.001), but not for CD40 on platelets. CONCLUSIONS: Patients with
      diabetes show increased coexpression of CD40 system, especially CD40L, which may
      create a proinflammatory and prothrombotic milieu for aggravating the development
      of atherosclerosis.

PMID- 14687898
TI  - Analysis of glycoconjugates in patients with oral squamous cell carcinoma.
AB  - BACKGROUND: Our aim was to examine the levels of glycoconjugates in plasma,
      erythrocyte membranes and buccal mucosa of healthy subjects and oral cancer
      patients. SUBJECTS AND METHODS: This study was conducted on 48 adult male oral
      cancer patients with various clinical stages (stage II to stage IV; 16 of each)
      and 16 disease-free healthy subjects who underwent surgical removal of impacted
      teeth or vestibuloplasty without inflammation. RESULTS: The plasma and tumor
      tissues glycoconjugates levels were significantly increased, whereas the
      erythrocyte membranes glycoconjugates were significantly decreased in oral cancer
      patients as compared to healthy subjects. The levels of glycoconjugates were
      gradually increased from stage II to stage IV in plasma and tumor tissues and
      decreased in erythrocyte membranes from stage II to stage IV of oral cancer
      patients. CONCLUSION: The increased plasma glycoconjugates can be due to the
      expense of erythrocyte membrane glycoconjugates or tumor tissue itself.

PMID- 14687899
TI  - Influence of fibrate treatment on malondialdehyde-modified LDL concentration.
AB  - BACKGROUND: Drug therapy is considered essential to the clinical prevention of
      atherosclerotic lesions in patients with diabetes mellitus (DM). METHODS: To
      confirm the effects of fibrate therapy, we determined low-density lipoprotein
      (LDL) size by gradient gel electrophoresis and malondialdehyde-modified LDL (MDA
      LDL) concentrations by enzyme-linked immunosolvent assay (ELISA) and clarified
      the association between apolipoprotein B (apo B) and MDA-LDL during the fibrate
      therapy. RESULTS: Mean MDA-LDL concentrations were higher in healthy men than in
      healthy women. There were no significant differences in mean MDA-LDL
      concentrations between age groups for males or females. According to the
      regression equation (y = 0.063x + 10.9) obtained for apo B and MDA-LDL
      concentrations with fibrate treatment, the apo B concentration in those may need
      to be decreased to 1260 mg/l to restore the MDA-LDL concentration to the control
      concentration (65 +/- 25 units/l). This slope of the apoB/MDA-LDL regression line
      was approximately half of that with no-drug treatment (y = 0.109x - 10.8).
      CONCLUSIONS: Fibrate therapy had an effect on reducing serum MDA-LDL
      concentration in diabetic patients.

PMID- 14687900
TI  - Protective effects of certoparin sodium, a low molecular weight heparin
      derivative, in experimental atherosclerosis.
AB  - BACKGROUND: The association of atherosclerosis and hypercholesterolemia is well
      known. Hypercholesterolemic diet-induced atherogenesis is a widely accepted
      experimental model that is amenable to exploration of both the disease as well as
      therapeutic interventions. We evaluated the role of low molecular weight heparin
      (LMWH) in modulating the early biochemical changes in atherogenesis. METHODS:
      Male Wistar rats (140 +/- 10 g) were fed an atherogenic diet comprising of normal
      rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil
      (CCT diet) for 2 weeks. While one of the CCT diet-fed group served as the
      untreated pathologic model, the other group received LMWH (Certoparin sodium,
      Troparin; 300 microg/day/rat s.c.) treatment, commencing on day 8 and continued
      for 1 week. RESULTS: Decreased concentrations of serum albumin and increased
      serum urea, uric acid and creatinine concentrations were normalized by LMWH
      treatment. The atherogenic diet induced abnormal rise in the activities of
      lactate dehydrogenase, aminotransferases and alkaline phosphatase, as well as the
      high serum cholesterol and triglyceride concentrations were restored to near
      control values in the treated group. LMWH administration prevented the
      hypertrophic cardiac histology and fatty changes in the liver in early
      atherogenesis. CONCLUSION: The present study encapsulates the early cellular
      abnormalities in the heart, liver and kidney tissues of atherogenic diet fed
      rats. Treatment with LMWH affords considerable protection to the tissues
      challenged by hypercholesterolemia, evidenced by its correction of lipemia and
      restoration of serum and tissue indices of injury, to normalcy. LMWH intervention
      minimized the atherogenic diet-induced histopathological lesions in heart, liver
      and kidney tissues.

PMID- 14687901
TI  - Oxidized low-density lipoprotein autoantibodies in patients with primary gout:
      effect of urate-lowering therapy.
AB  - BACKGROUND: Uric acid is a strong scavenger of reactive oxygen species, which are
      known to contribute to the development of atherosclerosis, while the incidence of
      atherosclerotic diseases is rather high in patients with gout. Among the
      established risk factors for atherosclerosis, oxidized LDL is believed to play a
      major role in its development and progression. Allopurinol and its active
      metabolite, oxypurinol, have been suggested to possess an antioxidant ability to
      scavenge the hydroxyl radical. Therefore, allopurinol may be beneficial in the
      prevention of LDL oxidation, as well as in the treatment of hyperuricemia. The
      objective of this work was to determine the degree of LDL oxidation in gout and
      the effect of allopurinol on LDL oxidation. METHODS: Age-matched male patients
      with primary intercritical gout and healthy male adults were included in the
      study. The serum concentrations of oxidized LDL autoantibodies and total
      antioxidant status were measured using an enzyme immunoassay. RESULTS: Serum
      concentrations of oxidized LDL autoantibodies were significantly higher in
      patients with gout than the control subjects (p < 0.05) and were significantly
      decreased after allopurinol treatment (p < 0.05), but not by benzbromarone
      treatment, in spite of the similar concentrations of uric acid and total
      antioxidant status in serum following their separate administration. CONCLUSIONS:
      Although the exact mechanism remains unclear, increased serum concentrations of
      oxidized LDL may play a role in the high incidence of coronary artery disease in
      gout. In addition, allopurinol may be more preferable to benzbromarone for
      treatment of gout in light of its inhibitory action toward LDL oxidation.

PMID- 14687902
TI  - Relation between age and gender differences in plasma triglyceride concentrations
      and coronary artery disease in Southern Turkey.
AB  - BACKGROUND: Coronary artery disease (CAD) is still a leading cause of morbidity
      and mortality in both genders in Turkey as well as other countries. The role of
      plasma triglycerides (TG) as a CAD risk factor has been controversial. We
      investigated the relation between age and gender differences in plasma TG and CAD
      in patients with angiographically proven CAD. METHODS: The study population
      consisted of 937 patients (605 males and 332 females, aged between 32 and 82
      years). The patients were divided into three age groups as < 45, 45-59 and > or =
      60 years. Risk factors were considered as hypertension, hyperlipidemia, diabetes
      mellitus, cigarette smoking and family history. Hypertriglyceridemia was defined
      as TG concentration > 150 mg/dl (> 1.69 mmol/l). RESULTS: Of the total, 608 had
      CAD. TG was an independent risk factor for CAD only in women (p < 0.05). There
      was also a positive correlation between TG concentrations and number of the
      diseased vessels only in women (p = 0.001, r = 0.2). CONCLUSION: High TG
      concentrations increase CAD risk more in women than in men in Southern Turkey.
      Triglycerides should be taken into consideration as an important risk factor
      especially in women > 45 years of age.

PMID- 14687903
TI  - Comparative vasodilating actions among terpenoids and flavonoids contained in
      Ginkgo biloba extract.
AB  - BACKGROUND: Comparative vasodilating actions of the constituents of Ginkgo biloba
      extract (GBE), terpenoids (bilobalide, ginkgolides A, B and C) and flavonoids
      (quercetin and rutin), were examined using rat aorta ring strips. METHODS:
      Cumulative administrations of GBE and its constituents were followed with the
      pretreatment of 5 micromol/l NE. RESULTS: GBE at 0.03 to 3 mg/ml had a potent
      concentration-dependent relaxation; by 70 +/- 4.5% (n = 6, P < 0.001) at 3 mg/ml.
      Terpenoids and flavonoids at 0.1 to 100 micromol/l had potent concentration
      dependent relaxation. At 100 micromol/l, bilobalide dilated by 17.6 +/- 3.9% (n =
      7, P < 0.05), and ginkgolides A, B and C also caused it to the almost same
      extent. Quercetin (100 micromol/l) caused a potent vasorelaxation by 49.9 +/-
      4.8% (n = 10, P < 0.001). Rutin at 100 micromol/l had weaker vasorelaxation; by
      13.7 +/- 3.2% (n = 6, P < 0.01). CONCLUSIONS: All constituents of GBE have the
      concentration-dependent vasorelaxtant effect. The potency of GBE's action was not
      made simply by addition of those of the constituents. Each constituent itself
      would contribute to the GBE-induced vasodilation, although the constituents have
      the complicated interactions with each other.

PMID- 14687904
TI  - Performance of four sources of cholesterol oxidase for serum cholesterol
      determination by the enzymatic endpoint method.
AB  - BACKGROUND: Cholesterol oxidase is used for the determination of serum
      cholesterol. It can be derived from Streptomyces, Pseudomonas fluorescens,
      Cellulomonas, and Brevibacterium. This study compared the performance
      characteristics of four enzymes in the endpoint cholesterol determination.
      METHODS: Using the Mega analyzer, we studied assay optimization, linearity,
      precision, recovery, interference, stability, and compared 110 patient samples.
      RESULTS: The linearity for the four enzymes was up to 13.0 mmol/l at the optimal
      enzyme activity. The average within-run CVs ranged from 1.6% to 1.9% and between
      day ranged from 2.8% to 3.0%, within the NCEP analytical criteria. The analytical
      recoveries obtained from four reagents ( approximately 96.5%) were excellent. The
      assays using these enzyme sources compared favorably with the commercial method
      and appeared accurate near the clinical decision cut-points. Hemoglobin
      concentration at 1.9 g/l interfered with the P. fluorescens cholesterol oxidase.
      Bilirubin caused a negative interference while lipemia generated a positive
      interference with all enzyme sources. Reagents were stable up to 6 weeks.
      CONCLUSIONS: Streptomyces, Cellulomonas, and Brevibacterium were essentially
      analytically equivalent. Streptomyces and Cellulomonas cholesterol oxidase are
      one-quarter as expensive Brevibacterium. Cellulomonas is a new source of
      cholesterol oxidase for determining serum cholesterol by the endpoint method.

PMID- 14687905
TI  - A rapid, simple measurement of human albumin in whole blood using a fluorescence
      immunoassay (I).
AB  - BACKGROUND: Human serum albumin (HSA) is the most abundant plasma protein and
      plays key a role in metabolism. The variation in albumin concentration provides
      valuable information related to metabolic diseases and diagnostic application.
      METHODS: We constructed two assay systems to quantify the albumin concentration.
      The immunoassay used a fluorescence (FL) dye to detect albumin in samples and
      employed the conventional chromatography as a separation system. The assay system
      consists of an anti-HSA-mAb or an HSA immobilized test strip in a disposable
      cartridge, a fluorescence-labeled detector buffer and a laser-fluorescence
      scanner. We mixed the sample with detector, loaded it onto a cartridge, incubated
      it for 10 min and measured the concentration of albumin in a laser-fluorescence
      scanner. We examined the comparability of assay with an automated BCG dye binding
      method using a Hitachi 747 biochemical analyzer. RESULTS: The correlation of
      coefficient between AT/AC as converted from the relative fluorescence units (RFU)
      and albumin concentration displayed reasonable reliability in both the
      competition and the inhibition assay systems (r = 0.998). Using the Bland-Altman
      difference plot analysis, we observed an acceptable agreement between two
      methods, the fluorescence immunochromatography assay (FL-ICA) and the automated
      BCG dye-binding method of a Hitachi biochemical analyzer, over the clinical
      relevant range of HSA concentrations. The coefficient of variation (CV) of within
      and between-run variation in the immunoassay system was < 8% and the recovery
      fell within 5% in each control sample. In addition to its reliable analytical
      performance, the assay with whole blood can be completed in 12 min using a one
      step operation without any pretreatment. CONCLUSION: The developed immunoassay
      system using fluorescence dye and lateral-flow chromatography is a simple, fast
      and reliable method for quantifying the albumin concentration in whole blood.

PMID- 14687906
TI  - Complex formation between human kallikrein 13 and serum protease inhibitors.
AB  - BACKGROUND: The kallikrein family is a group of 15 serine protease genes
      clustered on chromosome 19q13.4. Human kallikrein gene 13 (KLK13) is a member of
      this family and encodes for a trypsin-like, secreted serine protease (hK13).
      Given that other kallikreins are sequestered by serum protease inhibitors, we
      hypothesized that hK13 may also interact with similar inhibitors. Our objective
      was to identify serum protease inhibitors that interact with human hK13. METHODS:
      Recombinant hK13 produced in yeast was added to male and female sera and various
      biological fluids and the spiked samples were analyzed with an hK13 ELISA assay.
      Enzymatically active hK13 was 125I-labeled and used in in vitro reactions with
      candidate protease inhibitors and serum samples. The mixtures were then subjected
      to gel filtration and SDS-PAGE analysis. Candidate inhibitors were also tested in
      enzymatic assays of hK13 activity. RESULTS: The recovery of recombinant hK13 from
      male and female sera, measured by three versions of the hK13-ELISA, ranged from
      5% to 10%. The same recovery was obtained when serum samples from males and
      females were spiked with hK13 from amniotic fluid and seminal plasma. However,
      when hK13 was added to other biological fluids, such as amniotic fluid and breast
      milk, recovery ranged from 70% to 98%. In vitro analysis indicated that
      enzymatically active 125I-labeled hK13 forms SDS-stable complexes with alpha2
      antiplasmin, alpha2-macroglobulin and alpha1-antichymotrypsin. When added to
      serum, active hK13 formed stable complexes with molecular masses corresponding to
      hK13 and the inhibitors mentioned above. CONCLUSIONS: hK13 interacts and forms
      complexes with serum protease inhibitors, including alpha2-macroglobulin, alpha1
      antichymotrypsin and alpha2-antiplasmin.

PMID- 14687908
TI  - Effect of endogenous estrogen on endothelial function in women with coronary
      heart disease and its mechanism.
AB  - BACKGROUND: Estrogen promotes and modulates vascular endothelial function, which
      may be protective against development of atherosclerosis. Asymmetric
      dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, has
      been reported to be associated with the impairment of vascular endothelial
      function. Recent studies suggested estrogen replacement therapy lowers plasma
      concentrations of ADMA in healthy postmenopausal women. However, the relation
      between endogenous estrogen and ADMA and their effect on endothelial function in
      patients with coronary heart disease (CHD) remains unclear. METHODS: Flow
      mediated dilatation (FMD) and nitroglycerin-induced dilatation (NID) of the
      brachial arteries were detected by using high-resolution ultrasound in 33 women
      with CHD and 17 healthy controls. Plasma estradiol, ADMA, and lipid
      concentrations were also measured in all subjects. RESULTS: In comparison with
      control group, FMD and NID were significantly decreased in the CHD group (1.73 +/
      1.26% vs. 5.37 +/- 3.20%, p < 0.001 and 12.38 +/- 6.70% vs. 20.79 +/- 7.57%, p <
      0.01, respectively). Plasma estradiol concentrations in the CHD group were lower
      than in controls (27.80 +/- 12.28 vs. 43.83 +/- 14.30 pg/ml, p < 0.01), whereas
      ADMA concentrations in the CHD group were higher than in controls (3.39 +/- 1.07
      vs. 1.31 +/- 0.69 micromol/l, p < 0.001). Pearson correlation analysis determined
      that plasma estradiol concentrations were associated with FMD, NID, age, systolic
      pressure, diastolic pressure and ADMA (r = 0.610, p < 0.01; r = 0.392, p < 0.01;
      r = -0.589, p < 0.01; r= -0.364, p < 0.01; r = -0.350, p < 0.05; r = -0.553, p <
      0.01; respectively). Multiple linear stepwise regression analysis revealed that
      plasma estradiol concentrations was independently positively correlated with FMD
      (p < 0.005) and negatively correlated with ADMA (p < 0.05). CONCLUSIONS: Both FMD
      and NID are impaired in women with CHD. The decrease of endogenous estrogen
      concentrations and the increase of ADMA concentrations may involve the
      endothelial dysfunction in women with CHD.

PMID- 14687907
TI  - Hypertriglyceridemia in pregnancy does not contribute to the enhanced formation
      of remnant lipoprotein particles.
AB  - BACKGROUND: During pregnancy, serum cholesterol (TC) and triglyceride (TG)
      concentrations are known to increase significantly, but whether remnant
      lipoprotein particles (RLP) increase has not been shown. METHODS: We compared
      lipid profiles in 22 healthy pregnant women to 31 healthy nonpregnant women and
      24 patients with diabetes mellitus (DM), by measuring cholesterol and TG
      concentrations in major lipoprotein classes after HPLC separation and
      immunoseparation of RLP. RESULTS: Serum TG and TC concentrations were
      significantly higher in the pregnant group than in the healthy control or DM
      groups. Cholesterol and TG concentrations of all major lipoprotein classes were
      also significantly higher in the pregnant group than the control and DM groups,
      except for VLDL-TG in the DM group. RLP-C and RLP-TG concentrations were
      significantly higher in the pregnant group (8.7 mg/dl and 25.4 mg/dl on average)
      than the control group (2.4 mg/dl and 5.7 mg/dl), but not different from the DM
      group (8.8 mg/dl and 24.1 mg/dl). RLP-TG to RLP-C ratios were similar among the
      three groups and correlated with the VLDL-TG to VLDL-C ratio. The percentages of
      RLP-C in VLDL-C and RLP-TG in VLDL-TG in the pregnant group (15.9% and 15.7%)
      were significantly lower than those of the control (48.5% and 35.6%) and the DM
      (32.7% and 20.8%) groups. CONCLUSIONS: RLP increased moderately during gestation
      with the increase in VLDL and TG, but the percentage of RLP in VLDL was
      significantly lower in the pregnant women compared with the control and DM
      patients, suggesting that hypertriglyceridemia in pregnancy is not primarily due
      to an increase in the atherogenic RLP.

PMID- 14687909
TI  - Atorvastatin enhances cellular uptake of oxidized LDL in adipocytes from
      hypercholesterolemic rabbits.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) and
      CD36, a plausible pathway for the oxidized low-density lipoprotein (ox-LDL)
      uptake in monocytes, is highly expressed in adipocytes. Few studies have explored
      the cellular uptake of ox-LDL in adipocytes and its significance on
      atherosclerosis. METHODS: Rabbits on high-cholesterol diets were randomly
      assigned to either 1.5 mg/kg/day atorvastatin (n = 5) or starch (n = 5) for 2
      weeks. Subcutaneous adipose tissues were collected for adipocytes culture. The
      uptake of 125I-OxLDL in adipocytes was determined by a gamma-counter and each
      sample was normalized to protein concentration. Reverse transcription polymerase
      chain reaction (RT-PCR) was used to evaluate PPARgamma and CD36 mRNA expressions.
      RESULTS: Adipocytes took up 125I-OxLDL in a concentration-dependent manner. Two
      weeks of atorvastatin treatment enhanced the cellular uptake of 125I-OxLDL, which
      was closely related to the reduced plasma low-density lipoprotein cholesterol
      (LDL-C) concentrations and increased mRNA expressions of PPARgamma and CD36 in
      adipocytes, respectively. CONCLUSIONS: Adipocytes may be a potential pool for
      plasma ox-LDL, and atorvastatin can improve the ox-LDL uptake in adipocytes
      possibly through reducing cholesterol concentration and upregulating mRNA
      expressions of PPARgamma and CD36.

PMID- 14687910
TI  - Nitric oxide synthesis in chronic renal failure. Are plasma S-nitrosothiol levels
      elevated?

PMID- 14687911
TI  - A microplate assay for the determination of hemoglobin concentration.

PMID- 14687912
TI  - Increased protein thiol in the liver and plasma of rats in acute acetaminophen
      intoxication.

PMID- 14687913
TI  - The islet beta-cell.
AB  - The beta-cell is one of four major types of cells present in the islets of
      Langerhans, which are islands of cells distributed throughout the endocrine
      pancreas in most mammals. The beta-cell synthesizes and secretes the hormone
      insulin mainly in response to glucose but also in response to several nutrients,
      hormones and nervous stimuli. In adult rodents the beta-cell has a slow mitotic
      rate. Recent studies provide novel insights into the functions of the beta-cell.
      The presence of functional insulin-like growth factor-1 and insulin receptors and
      components of their signaling pathway indicate an important role for insulin/IGF
      1 signaling in the regulation of beta-cell function. Further, the recent
      discovery of glucokinase (GK) and the ATP-dependent potassium channels on insulin
      secretory granules, the detection of AMP-protein kinase in the beta-cell and the
      identification of a new beta-cell transcription factor, mMafA, are some exciting
      new areas of research currently underway to further understand the complex
      pathways that regulate the functions of beta-cells.

PMID- 14687914
TI  - Rheumatoid arthritis: regulation of synovial inflammation.
AB  - Rheumatoid arthritis (RA) is a systemic, inflammatory autoimmune disorder that
      presents as a symmetric polyarthritis associated with swelling and pain in
      multiple joints, often initially occurring in the joints of the hands and feet.
      Articular inflammation causes activation and proliferation of the synovial
      lining, expression of inflammatory cytokines, chemokine-mediated recruitment of
      additional inflammatory cells, as well as B cell activation with autoantibody
      production. A vicious cycle of altered cytokine and signal transduction pathways
      and inhibition of programmed cell death contribute to synoviocyte and osteoclast
      mediated cartilage and bone destruction. A combination of targeted interventions
      at various stages in the pathogenesis of RA will likely be required to control
      symptoms in certain patients with this complex and potentially disabling disease.
      The regulation of rheumatoid synovial inflammation will be reviewed, followed by
      a brief summary of the therapeutic implications of these advances, including
      strategies targeting key cytokines, signal transduction molecules, co-stimulatory
      molecules, B cells, chemokines, and adhesion molecules.

PMID- 14687915
TI  - The translationally controlled tumour protein (TCTP).
AB  - The translationally controlled tumour protein (TCTP) is a highly conserved
      protein that is widely expressed in all eukaryotic organisms. Based on its
      sequence, TCTP was listed as a separate protein family in protein databases but
      the recent elucidation of the solution structure of the fission yeast orthologue
      places it close to a family of small chaperone proteins. The molecular functions
      determined so far, Ca(2+)- and microtubule-binding, have been mapped to an alpha
      helical region of the molecule. TCTP expression is highly regulated both at the
      transcriptional and translational level and by a wide range of extracellular
      signals. TCTP has been implicated in important cellular processes, such as cell
      growth, cell cycle progression, malignant transformation and in the protection of
      cells against various stress conditions and apoptosis. In addition, an
      extracellular, cytokine-like function has been established for TCTP, and the
      protein has been implicated in various medically relevant processes.

PMID- 14687916
TI  - Antithrombin: in control of coagulation.
AB  - Antithrombin is a serine proteinase inhibitor (serpin) which controls the process
      of coagulation. It has a well defined structure, consisting of three beta-sheets,
      nine alpha-helices and a reactive centre loop (RCL). The RCL contains the
      reactive centre which harbours a bait sequence for target proteases; cleavage
      results in inhibition by a unique mechanism. The inhibitory activity of
      antithrombin is controlled by its interaction with the co-factor, heparin, which
      accelerates its interaction with target proteases. This ensures that heparin and
      its newer derivatives, such as heparin pentasaccharide, are the mainstay
      therapeutics for control of thrombosis or inappropriate clotting. The clinical
      importance of antithrombin is manifested by its clear association with thrombosis
      when deficiency states occur.

PMID- 14687917
TI  - Nitric oxide release by hemocytes of the mussel Mytilus galloprovincialis Lmk was
      provoked by interleukin-2 but not by lipopolysaccharide.
AB  - As other marine and land mollusks, mussels have special cells in charge of the
      immune function called hemocytes. The activation of these cells leads to a series
      of events that end up in phagocytosis and in secretion of digestive enzymes that
      eliminate the pathogen. The production of nitric oxide is among the early
      activation processes. Contrary to what happens in cells of vertebrates and of
      other species of mollusks, in hemocytes of Mytilus galloprovincialis, LPS did not
      induce secretion of NO to the medium. However, human IL-2 provoked an important
      increase in NO production. The maximal synthesis of NO was detected after the
      hemocytes were incubated with the cytokine for 24h. In both stimulated and non
      stimulated cells, Western blotting showed the presence of a protein of 130kDa,
      recognized by anti-mouse iNOS. Therefore, the higher production of NO can only be
      explained as a direct action of some effector upon the nitric oxide synthetase.
      NO production decreased by the action of H-89, a powerful inhibitor of the cAMP
      dependent protein kinase (PKA). This suggests the involvement of PKA in the
      pathway of NO synthesis.

PMID- 14687918
TI  - Induction of fibulin-5 gene is regulated by tropoelastin gene, and correlated
      with tropoelastin accumulation in vitro.
AB  - Fibulin-5 (also known as DANCE) is an elastin-binding protein that is thought to
      play a role in elastogenesis. We examined the relationship between the gene
      expression of fibulin-5 and the gene expression and accumulation of tropoelastin
      by comparing elastin-producing cells (human gingival fibroblasts) with non
      elastin-producing cells (human periodontal ligament fibroblasts) by Northern blot
      analysis. Fibulin-5 gene induction was found only in elastin-producing cells.
      Induction of the fibulin-5 gene in elastin-producing cells occurred after
      induction of the tropoelastin gene, and the fibulin-5 level was reduced upon RNA
      interference-mediated down-regulation of tropoelastin. Fibulin-5 gene induction
      was also correlated with a rapid increase of tropoelastin accumulation within the
      cell layer. These results may suggest that the fibulin-5 gene induction is
      directly or indirectly regulated by tropoelastin gene expression and plays a role
      in the accumulation of elastic fibers within matrices.

PMID- 14687919
TI  - Novel aroylhydrazone and thiosemicarbazone iron chelators with anti-malarial
      activity against chloroquine-resistant and -sensitive parasites.
AB  - Iron (Fe) is crucial for cellular proliferation, and Fe chelators have shown
      activity at preventing the growth of the malarial parasite in cell culture and in
      animal and human studies. We investigated the anti-malarial activity of novel
      aroylhydrazone and thiosemicarbazone Fe chelators that show high activity at
      inhibiting the growth of tumour cells in cell culture [Blood 100 (2002) 666].
      Experiments with the chelators were performed using the chloroquine-sensitive,
      3D7, and chloroquine-resistant, 7G8, strains of Plasmodium falciparum in vitro.
      The new ligands were significantly more active in both strains than the Fe
      chelator in widespread clinical use, desferrioxamine (DFO). The most effective
      chelators examined were 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone and
      2-hydroxy-1-naphthylaldehyde-4-phenyl-3-thiosemicarbazone. The anti-malarial
      activity correlates with anti-proliferative activity against neoplastic cells
      demonstrated in a previous study. Our studies suggest that this class of
      lipophilic chelators may have potential as useful agents for the treatment of
      malaria.

PMID- 14687920
TI  - Dipeptidyl peptidase IV activity and/or structure homologues (DASH) and their
      substrates in cancer.
AB  - Post-translational modification of proteins is an important regulatory event.
      Numerous biologically active peptides that play an essential role in
      cancerogenesis contain an evolutionary conserved proline residue as a proteolytic
      processing regulatory element. Proline-specific proteases could therefore be
      viewed as important "check-points". Limited proteolysis of such peptides may lead
      to quantitative but, importantly, due to the change of receptor preference, also
      qualitative changes of their signaling potential. Dipeptidyl peptidase-IV (DPP
      IV, EC 3.4.14.5, identical with CD26) was for many years believed to be a unique
      cell membrane protease cleaving X-Pro dipeptides from the N-terminal end of
      peptides and proteins. Subsequently, a number of other molecules were discovered,
      exhibiting various degree of structural homology and DPP-IV-like enzyme activity,
      capable of cleaving similar set of substrates. These comprise for example,
      seprase, fibroblast activation protein alpha, DPP6, DPP8, DPP9, attractin, N
      acetylated-alpha-linked-acidic dipeptidases I, II and L, quiescent cell proline
      dipeptidase, thymus-specific serine protease and DPP IV-beta. It is tempting to
      speculate their potential participation on DPP-IV biological function(s).
      Disrupted expression and enzymatic activity of "DPP-IV activity and/or structure
      homologues" (DASH) might corrupt the message carried by their substrates,
      promoting abnormal cell behavior. Consequently, modulation of particular enzyme
      activity using e.g. DASH inhibitors, specific antibodies or DASH expression
      modification may be an attractive therapeutic concept in cancer treatment. This
      review summarizes recent information on the interactions between DASH members and
      their substrates with respect to their possible role in cancer biology.

PMID- 14687921
TI  - Active and inactive ecto-5'-nucleotidase variants in liver of control and
      dystrophic Lama2dy mice.
AB  - The ecto-5'-nucleotidase (eNT) activity and the eNT protein content in liver of
      normal and merosin-deficient dystrophic Lama2dy mice were studied. After the
      solubilization procedure, the eNT activity in the final extract was 9.2+/-2.5U/mg
      (nmol of phosphate released from AMP per min and per mg protein) in normal liver,
      and it rose to 16.1+/-3.9U/mg (P=0.005) in dystrophic liver. The increase of
      activity was less pronounced in Lama2dy liver (1.7-fold) than the one reported in
      muscle (four-fold), which probably reflects the lower content of merosin in
      liver. Similarly to muscle, liver contained active and inactive eNT, as
      demonstrated by the higher level of immunoreactive protein in normal than in
      dystrophic liver in Western blots performed with samples containing the same
      units of eNT activity. PNGase F digestion decreased the size of liver and muscle
      eNT from 72 and 69kDa, to 63 and 60kDa. Oligoglycan cleavage did not alter eNT
      activity or the sedimentation coefficient, revealing that oligosaccharides are
      not required for catalysis or for maintaining the dimeric structure. The eNT
      protein content in samples of normal liver decreased by 55 or 80% after the
      trypsinolysis of native or deglycosylated enzyme, but the activity did not
      change. Such a high proportion of inactive eNT is unlikely to come from aged
      enzyme, which suggests the involvement of inactive enzyme in non-catalytic
      actions.

PMID- 14687922
TI  - Highly reactive cysteine residues are part of the substrate binding site of
      mammalian dipeptidyl peptidases III.
AB  - Dipeptidyl peptidase III (DPP III) is a cytosolic zinc-exopeptidase involved in
      the intracellular protein catabolism of eukaryotes. Although inhibition by thiol
      reagents is a general feature of DPP III originating from various species, the
      function of activity important sulfhydryl groups is still inadequately
      understood. The present study of the reactivity of these groups was undertaken in
      order to clarify their biological significance. The inactivation kinetics of
      human and rat DPP III by sulfhydryl reagent p-hydroxy-mercuribenzoate (pHMB) was
      monitored by determination of the enzyme's residual activity with fluorimetric
      detection. Inactivation of this human enzyme exhibited pseudo-first-order
      kinetics, suggesting that all reactive SH-groups have equivalent reactivity, and
      the second-order rate constant was calculated to be 3523+/-567M(-1)min(-1). Rat
      DPP III was hyperreactive to pHMB and showed biphasic kinetics indicating two
      classes of reactive SH-groups. The second-order rate constants of 3540M(-1)s(-1)
      for slower reacting sulfhydryl, and 21,855M(-1)s(-1) for faster reacting
      sulfhydryl were obtained from slopes of linear plots of pseudo-first-order
      constants versus reagent concentration. Peptide substrates protected both
      mammalian DPPs III from inactivation by pHMB. Physiological concentrations of
      biological thiols and H(2)O(2) inactivated the rat DPP III. Human enzyme was
      resistant to H(2)O(2) attack and less affected by reduced glutathione (GSH) than
      the rat homologue. A significantly lower DPP III level, determined by activity
      measurement and Western blotting, was found in the cytosols of highly oxygenated
      rat tissues. These results provide kinetic evidence that cysteine residues are
      involved in substrate binding of mammalian DPPs III.

PMID- 14687923
TI  - Unfolding and inactivation during thermal denaturation of an enzyme that exhibits
      phytase and acid phosphatase activities.
AB  - The thermostability of an enzyme that exhibits phytase and acid phosphatase
      activities was studied. Kinetics of inactivation and unfolding during thermal
      denaturation of the enzyme were compared. The loss of phytase activity on thermal
      denaturation is most suggestive of a reversible process. As for acid phosphatase
      activities, an interesting phenomenon was observed; there are two phases in
      thermal inactivation: when the temperature was between 45 and 50 degrees C, the
      thermal inactivation could be characterized as an irreversible inactivation which
      had some residual activity and when the temperature was above 55 degrees C, the
      thermal inactivation could be characterized as an irreversible process which had
      no residual activity. The microscopic rate constants for the free enzyme and
      substrate-enzyme complex were determined by Tsou's method [Adv. Enzymol. Relat.
      Areas Mol. Biol. 61 (1988) 381]. Fluorescence analyses indicate that when the
      enzyme was treated at temperatures below 60 degrees C for 60 min, the
      conformation of the enzyme had no detectable change; when the temperatures were
      above 60 degrees C, some fluorescence red-shift could be observed with a decrease
      in emission intensity. The inactivation rates (k(+0)) of free enzymes were faster
      than those of conformational changes during thermal denaturation at the same
      temperature. The rapid inactivation and slow conformational changes of phytase
      during thermal denaturation suggest that inactivation occurs before significant
      conformational changes of the enzyme, and the active site of this enzyme is
      situated in a relatively fragile region which makes the active site more flexible
      than the molecule as a whole.

PMID- 14687924
TI  - The pivotal role of scavenger receptor CD36 and phagocyte-derived oxidants in
      oxidized low density lipoprotein-induced adhesion to endothelial cells.
AB  - Adhesion of phagocytes to endothelial cells constitutes a crucial step in
      atherogenesis. Oxidized low density lipoproteins (LDL) are supposed to facilitate
      the adhesion process. We investigated the molecular mechanisms by which mildly
      and extensively hypochlorite-oxidized LDL force adhesion of murine macrophages
      and human neutrophils to human umbilical venous endothelial cells. After 1h of co
      incubation of macrophages, endothelial cells, and lipoproteins adhesion
      significantly increased to 160+/-13% (S.E.M., n=5) in the presence of mildly
      oxidized lipoprotein, and 210+/-11% (S.E.M., n=5) in the presence of extensively
      oxidized lipoprotein. Similar results were obtained with neutrophils. CD36
      antibody (FA6-152) significantly reduced adhesion to 102+/-7% (S.E.M., n=5) using
      mildly oxidized low density lipoprotein and to 179+/-16% (S.E.M., n=5) using
      extensively oxidized low density lipoprotein. Native high density lipoprotein and
      to a lesser extent methionine-oxidized high density lipoprotein significantly
      counteracted the effects of low density lipoprotein. Prior incubation of
      endothelial cells with modified lipoproteins followed by their removal and
      subsequent incubation with macrophages or neutrophils resulted in only minor
      changes of adhesion. This suggests that the direct contact of low density
      lipoprotein with phagocytes followed by activation of a respiratory burst with
      release of reactive oxygen species facilitates the adhesion process. Accordingly,
      the addition of antioxidants (superoxide dismutase and catalase) to the co
      incubation medium was followed by a significant decrease in phagocyte adhesion.
      It is concluded that oxidized low density lipoprotein-induced respiratory burst
      activation of phagocytes with subsequent release of oxidants constitutes a
      crucial step in promoting the adhesion of phagocytes to endothelial cells.

PMID- 14687925
TI  - Molecular cloning of a novel variant of the rat soluble guanylate cyclase beta2
      subunit.
AB  - Soluble guanylate cyclases (sGCs) are heterodimeric enzymes consisting of alpha
      and beta subunits and catalyze the formation of cGMP from GTP. The beta1 subunit
      has been characterized in detail, whereas the function and physiological role of
      the beta2 subunit are poorly understood. In this study, I isolated two distinct
      cDNA fragments for the beta2 subunit of sGC (beta2a and beta2b) from a rat brain
      cDNA library by 3' rapid amplification of cDNA ends using degenerate sense
      primers based on amino acid sequences conserved among membrane-bound guanylate
      cyclases. The deduced amino acid sequence of beta2a is identical with the
      corresponding sequence of the previously described beta2 subunit, whereas that of
      beta2b is C-terminally shorter by 46 amino acids and thus does not contain a
      consensus sequence for isoprenylation/carboxymethylation. Reverse transcription
      polymerase chain reaction (RT-PCR) analysis demonstrated that both variants are
      expressed in various tissues, including kidney, liver, and brain. Although the
      functional significance of the C-terminal region containing the consensus
      sequence for isoprenylation/carboxymethylation of beta2a remains unclear yet, it
      is likely that these beta2 subunits play some physiological or pathophysiological
      role in various tissues.

PMID- 14687926
TI  - Differential effects of gadolinium chloride on Kupffer cells in vivo and in
      vitro.
AB  - Gadolinium chloride (GdCl) is commonly used to study the role of Kupffer cells in
      liver disease in vivo. The in vitro effects of GdCl on cultured Kupffer cells are
      poorly characterised. The aim of this study was to characterise rat Kupffer cell
      TNFalpha production, phagocytic function, and ED1 and ED2 antigen expression
      following the administration of GdCl. For in vivo experiments, rats received
      10mg/kg GdCl IV or sterile saline. Lipopolysaccharide 3mg/kg IP (LPS) was
      administered 4h prior to sacrifice on Days 1-3, 5 or 8 following GdCl injection.
      Hepatic ED1 and ED2 positive macrophage numbers and TNFalpha mRNA levels were
      determined. For in vitro experiments, Kupffer cells were cultured in the presence
      of 0-270 microM GdCl for 24h following which viability, TNFalpha protein
      production in response to LPS (10 ng/ml), phagocytosis, and ED1 and ED2 staining
      were evaluated. In vivo, the proportion of ED1 positive cells which were ED2
      positive was reduced from 87 to 3% and hepatic TNFalpha mRNA levels following LPS
      declined by 60% over Days 1-5 after injection of GdCl (P<0.01). In vitro,
      phagocytosis declined with increasing concentrations of GdCl. GdCl (0-27 microM)
      did not effect cultured Kupffer cell viability, TNFalpha production, ED1 or ED2
      staining. We conclude that GdCl significantly reduces ED2 expression by Kupffer
      cells in vivo. In vitro, GdCl has a dose dependent effect on phagocytosis but
      only effects viability and TNFalpha production at high concentrations. ED2
      expression of cultured Kupffer cells is not affected by GdCl.

PMID- 14687927
TI  - Tyrosine phosphorylation signalling dependent on 1alpha,25(OH)2-vitamin D3 in rat
      intestinal cells: effect of ageing.
AB  - In intestinal cells, as in other target cells, 1alpha,25(OH)(2)D(3) elicits long
      term and short-term responses which involve genomic and non-genomic mode of
      actions, respectively. There is evidence indicating that activation of tyrosine
      phosphorylation pathways may participate in the responses induced by
      1alpha,25(OH)(2)D(3) through its non-genomic mechanism. In this study we have
      evaluated the involvement of 1alpha,25(OH)(2)D(3) in the tyrosine phosphorylation
      of PLCgamma and MAPK (ERK1/2) in enterocytes from young (3 months) and aged (24
      months) rats. Immunochemical analysis revealed that the hormone stimulates
      PLCgamma tyrosine phosphorylation in young rat enterocytes. Hormone effect on
      PLCgamma is rapid, peaking at 2 min (+100%), is dose-dependent (10(-10) to 10(
      8)M) and decreases with ageing. 1alpha,25(OH)(2)D(3) also induces the
      phosphorylation and activation of the mitogen-activated-protein kinases ERK1 and
      ERK2, effect which was evident at 1 min (three-fold) and reached a maximum at 2
      min (six-fold). Hormone-dependent ERK1 and ERK2 phosphorylation and activity is
      greatly reduced in enterocytes from old rats. In both, young and aged animals,
      1alpha,25(OH)(2)D(3)-induced PLCgamma and ERK1/2 phosphorylation was effectively
      suppressed by the tyrosine kinase inhibitor genistein (100 uM) and suppressed to
      a great extent by PP1, an inhibitor of c-Src kinases. LY294002, a specific
      inhibitor of PI3 kinase (PI3K), enzyme with an important role in mitogenesis, did
      not affect hormone-dependent ERK1/2 phosphorylation, indicating that PI3K is not
      involved in 1alpha,25(OH)(2)D(3)-induced MAPK activation. In agreement with this
      data, enzyme activity assays and tyrosine phosphorylation of the regulatory
      subunit (p85) of PI3K showed that the hormone has no effect on the enzyme
      activity in rat enterocytes. Taken together, the present study suggest that in
      intestinal cells, tyrosine phosphorylation is an important mechanism of
      1alpha,25(OH)(2)D(3) involved in PLCgamma and MAPK regulation and that this
      mechanism is impair with ageing.

PMID- 14687928
TI  - Hydrogen peroxide induces the dissociation of GroEL into monomers that can
      facilitate the reactivation of oxidatively inactivated rhodanese.
AB  - Although, several studies have been reported on the effects of oxidants on the
      structure and function of other molecular chaperones, no reports have been made
      so far for the chaperonin GroEL. The ability of GroEL to function under oxidative
      stress was investigated in this report by monitoring the effects of hydrogen
      peroxide (H(2)O(2)) on the structure and refolding activity of this protein.
      Using fluorescence spectroscopy and light scattering, we observed that GroEL
      showed increases in exposed hydrophobic sites and changes in tertiary and
      quaternary structure. Differential sedimentation, gel electrophoresis, and
      circular dichroism showed that H(2)O(2) treated GroEL underwent irreversible
      dissociation into monomers with partial loss of secondary structure. Relative to
      other proteins, GroEL was found to be highly resistant to oxidative damage.
      Interestingly, GroEL monomers produced under these conditions can facilitate the
      reactivation of H(2)O(2)-inactivated rhodanese but not urea-denatured rhodanese.
      Recovery of approximately 84% active rhodanese was obtained with either native or
      oxidized GroEL in the absence of GroES or ATP. In comparison, urea-denatured
      GroEL, BSA and the refolding mixture in the absence of proteins resulted in the
      recovery of 72, 50, and 49% rhodanese activity, respectively. Previous studies
      have shown that GroEL monomers can reactivate rhodanese. Here, we show that
      oxidized monomeric GroEL can reactivate oxidized rhodanese suggesting that GroEL
      retains the ability to protect proteins during oxidative stress.

PMID- 14687929
TI  - LDL transcytosis by protein membrane diffusion.
AB  - Endothelial cell (EC) cultures of different, selected vascular beds and/or organs
      were screened for receptor-mediated transport of proteins with a semipermeable
      filter assay. In SVEC4-10 cells, a mouse lymphoid endothelial cell line,
      orosomucoid, albumin, insulin and LDL were transcytosed from the apical (luminal)
      to basal (abluminal) side by a receptor-mediated pathway. Specific LDL
      transcytosis involved transport of intact LDL. A pathway of degradation of LDL
      and basal release involved vesicles in transport to lysosomes and amino acid
      merocrine secretion. This newly described transcellular passage of LDL via
      lysosomes, as well as the standard pathway, were reduced to 70% by PEG(50)
      cholesterol (PEG-Chol). Combined results of temperature-dependence analysis and
      PEG(50)-cholesterol sensitivity show that two pathways contribute to general LDL
      transcellular passage. We suggest a mechanism of domain hopping by protein
      membrane diffusion of receptors as the pathway for intact LDL delivery. Based on
      theoretical considerations we propose that active transport by protein membrane
      diffusion can be facilitated by an organizational structure of lipid microdomains
      and polar cellular organization.

PMID- 14687930
TI  - GS-Finder: a program to find bacterial gene start sites with a self-training
      method.
AB  - In this paper, a self-training method is proposed to recognize translation start
      sites in bacterial genomes without a prior knowledge of rRNA in the genomes
      concerned. Many features with biological meanings are incorporated, including
      mononucleotide distribution patterns near the start codon, the start codon
      itself, the coding potential and the distance from the most-left start codon to
      the start codon. The proposed method correctly predicts 92% of the translation
      start sites of 195 experimentally confirmed Escherichia coli CDSs, 96% of 58
      reliable Bacillus subtilis CDSs and 82% of 140 reliable Synechocystis CDSs.
      Moreover, the self-training method presented might also be used to relocate the
      translation start sites of putative CDSs of genomes, which are predicted by gene
      finding programs. After post-processing by the method presented, the improvement
      of gene start prediction of some gene-finding programs is remarkable, e.g., the
      accuracy of gene start prediction of Glimmer 2.02 increases from 63 to 91% for
      832 E. coli reliable CDSs. An open source computer program to implement the
      method, GS-Finder, is freely available for academic purposes from
      http://tubic.tju.edu.cn/GS-Finder/.

PMID- 14687931
TI  - Accumulation of 5-phosphoribosyl-1-pyrophosphate in human CCRF-CEM leukaemia
      cells treated with antifolates.
AB  - Amido phosphoribosyltransferase (APRT) catalyzes the first step of the de novo
      biosynthesis of purine nucleotides, the conversion of 5-phosphoribosyl-1
      pyrophosphate (PRPP) into 5-phosphoribosylamine (PRA). APRT is a valid target for
      development of inhibitors as anticancer drugs. We have developed a thin layer
      chromatographic assay for PRPP extracted from cells. Using coupling enzymes, PRPP
      with excess [2-14C]orotate (OA) is quantitatively converted to [2-14C]OMP and
      then [2-14C]UMP with hydrolysis of the PPi. The reaction products are isolated on
      poly(ethyleneimine)-cellulose (PEI-C) chromatograms. Human CCRF-CEM leukaemia
      cells growing in culture have been exposed to a number of antifolates and their
      effects upon cellular levels of PRPP determined. The steady-state level of PRPP
      measured in CCRF-CEM cells was 102+/-11 microM. Following addition of an
      antifolate to a culture, accumulation of PRPP in cells indicates the degree of
      inhibition of APRT. In human CCRF-CEM leukaemia cells, lometrexol (LTX), 2,4
      diamino-6-(3,4,5-trimethoxybenzyl)-5,6,7,8-tetrahydro-quinazoline (PY899),
      methotrexate (MTX), N(alpha)(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L
      ornithine (PT523), piritrexim (PTX), metoprine, 2,4-diamino-6-(3,4,5
      trimethoxyanilino)-methylpyrido[3,2-d]pyrimidine (PY873) and multitargeted
      antifolate, N-[4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5
      yl)ethyl]benzoyl]-L-glutamic acid (MTA) directly or indirectly induce inhibition
      of APRT indicated by time-courses for accumulation of PRPP to maximum values of 3
      12-fold. These data indicate that LTX induces the most potent inhibition of APRT.

PMID- 14687932
TI  - Somatic mutations to arginine residues affect the binding of human monoclonal
      antibodies to DNA, histones, SmD and Ro antigen.
AB  - Autoantibodies to a wide variety of antigens are associated with systemic lupus
      erythematosus (SLE). Antibodies to double-stranded DNA (anti-dsDNA) are thought
      to be particularly closely related to tissue damage and disease activity in SLE.
      Autoantibodies to histones, Sm and Ro are found in patients with SLE, but their
      role in pathogenesis is unclear. Using a transient expression system, we
      previously showed that particular sequence motifs in CDRs of light chains derived
      from the human Vlambda gene 2a2 are very important in determining their ability
      to form a DNA-binding site, when paired with the heavy chain of the human
      monoclonal anti-dsDNA antibody B3. These motifs are often sites of somatic
      mutation and/or contain arginine residues. In the experiments reported in this
      paper, the same expression system was used to show that these CDR motifs also
      affect binding to histones, Ro antigen and Sm antigen, but that binding to
      different antigens is affected in diverse ways by particular changes in the
      sequence of the CDRs. The heavy chain also plays a role in binding to these
      antigens. Pairing of the same range of 11 2a2 derived light chains with the heavy
      chain of a different anti-DNA antibody, 33.H11, gave reduced ability to bind DNA
      in comparison with the results obtained using the B3 heavy chain. Computer
      generated models of the three-dimensional structures of these heavy/light chain
      combinations were used to define the positions occupied by the important sequence
      motifs at the binding sites of these antibodies, and to explain the different
      effects exerted by arginine residues at different positions in the light chains.

PMID- 14687933
TI  - Toll-like receptor gene family and TIR-domain adapters in Danio rerio.
AB  - The toll-like family of receptors (TLR) is an ancient pattern recognition
      receptor family, conserved from insects to mammals. We have identified in
      zebrafish (Danio rerio) 19 putative TLR variants, the orthologs of mammalian TLR2
      5, 7-9, a fish specific receptor type group and three putative splice variants.
      One receptor is very close to mammalian TLR1, 6 and 10 and seems to be their
      common ancestor. However, in contrast to the pufferfish, Fugu rubripes, we found
      two receptors homologous to TLR4, showing that lack of TLR4 is not general for
      fish. In addition, we identified two members close to mammalian TLR8 and five
      members close to FuguTLR21 and goldfish TLR, a TLR group which now has only been
      found in fish. By RT-PCR we showed that all TLR are widely expressed in adult
      tissues, but also at different stages of development. All these TLRs contain very
      conserved toll/interleukin-1 receptor (TIR) domains able to interact with TIR
      domain of adapter molecules. We demonstrate here that TIR-domain containing
      adapters MyD88 and SARM are present in zebrafish, showing that TLR adapter
      molecules are highly conserved in evolution.

PMID- 14687934
TI  - Expression analysis of the Toll-like receptor and TIR domain adaptor families of
      zebrafish.
AB  - The zebrafish genomic sequence database was analysed for the presence of genes
      encoding members of the Toll-like receptors (TLR) and interleukin receptors (IL
      R) and associated adaptor proteins containing a TIR domain. The resulting
      predictions show the presence of one or more counterparts for the human TLR1,
      TLR2, TLR3, TLR4, TLR5, TLR7, TLR8, TLR9, IL-1R and IL-18R genes and one copy of
      the adaptor genes MyD88, MAL, TRIF and SARM. In contrast to data for the
      pufferfish Fugu rubripes, zebrafish has two genes that are highly similar to
      human TLR4. In addition, one fish-specific TLR group can be distinguished that is
      closely related to the Drosophila melanogaster Toll-9 gene. The sequence of
      cloned cDNAs for TLR4, TLR2 and MyD88 show the same intron-exon organisation as
      in the human counterparts. Expression analysis using reverse transcriptase-PCR
      (RT-PCR) shows that 17 of the predicted zebrafish TLR genes and all the genes
      encoding adaptor proteins are expressed in the adult stage. A subset of the TLR
      genes are expressed at higher levels in fish infected with the pathogen
      Mycobacterium marinum. The induced genes include the homologues of the human TLR1
      and TLR2 genes, whose functions are associated with mycobacterial infections,
      underscoring the suitability of zebrafish as a model for analysis of the
      vertebrate innate immune system.

PMID- 14687935
TI  - Carboxypeptidase N: a pleiotropic regulator of inflammation.
AB  - Carboxypeptidase N (CPN) is a plasma zinc metalloprotease, which consists of two
      enzymatically active small subunits (CPN1) and two large subunits (CPN2) that
      protect the protein from degradation. CPN cleaves carboxy-terminal arginines and
      lysines from peptides found in the bloodstream such as complement anaphylatoxins,
      kinins, and creatine kinase MM (CK-MM). By removing only one amino acid, CPN has
      the ability to change peptide activity and receptor binding. CPN is a member of a
      larger family of carboxypeptidases, many of which also cleave arginine and
      lysine. Because of the highly conserved active sites and the possible redundant
      functions of carboxypeptidases, it has been difficult to elucidate the role of
      CPN in disease processes. The future use of gene ablation technology may be the
      most appropriate way to understand the function of CPN in vivo.

PMID- 14687936
TI  - Analysis of low molecular weight intracellular associations of a human mannan
      binding lectin (MBL).
AB  - Human mannan binding lectin (MBL) is a member of the collectins, a group of
      proteins that contain a dual structure with a lectin and a collagenous moieties.
      The collectins are considered as major actors of innate immunity. We report the
      presence of low molecular weight intracellular MBL forms in human hepatocytic
      cell lysates, with binding capacities associated to its lectin and/or its
      collagen moiety. Competition with D-mannose and with antibodies directed against
      the lectin binding site of MBL indicate that the 60 kDa form represents an
      intracellular association of MBL through its lectin moiety. The effects of
      collagenase or MBL associated serine proteases (MASPs) from a MBL deficient
      plasma, gave evidence that the 60 KDa form contains also collagen and suggested
      the binding of a ligand to this collagen part. These results show that this
      intracellular form of MBL shares binding properties with circulating MBL. The
      binding potential of the lectin and the collagenous parts of precursor forms of
      intracellular MBL may suggest that they behave as molecular chaperone. The
      complexity of MBL structure and functions deserves further investigation on other
      intracellular forms of MBL.

PMID- 14687937
TI  - Segmental flexibility and avidity of IgM in the interaction of polyvalent
      antigens.
AB  - We prepared IgG and IgM with identical combining sites to a hapten, (4-hydroxy-3
      nitrophenyl)acetic acid (NP), and used surface plasmon resonance to evaluate the
      association constants (Ka) in interactions of these antibodies (Abs) with
      antigens (Ags) which differed in the size of carriers and NP valence as well as
      in the stoichiometry of Ag to Ab in the immune complexes. It was found that IgM
      was unable to form an Ag1Ab1 complex with the highly haptenated Ag, NP(18.6)
      bovine serum albumin (BSA), such that one NP(18.6)-BSA molecule was held by
      multiple contacts with Fab arms from five subunits, although IgM was capable of
      forming an Ag4Ab1 complex in which each subunit was bound to one NP(18.6)-BSA
      molecule. IgM was superior to IgG in interactions with large Ags of low hapten
      density. The Ka values of IgM to these Ags were estimated to be approximately
      1x10(9) M(-1), about 20-fold higher than those of IgG. Reduction of inter-subunit
      and inter-chain disulfide bonds resulted in a decrease in Ka values to large Ags
      but no change in those to small Ags.

PMID- 14687938
TI  - Partial reconstitution of V(D)J rearrangement and lymphocyte development in RAG
      deficient mice expressing inducible, tetracycline-regulated RAG transgenes.
AB  - Previously, we described a tetracycline-based autoregulatory system for inducible
      gene expression in mammalian cells and transgenic mice [Proc. Natl. Acad. Sci.
      U.S.A. 92 (1995) 6522]. We have tested the ability of this system to drive
      functional expression in vivo of the V(D)J recombination activating genes, RAG1
      and RAG2. In induced transgenic mice, transgenic RAG1 and RAG2 mRNA is observed
      in thymus and spleen, and expression of both transgenes on the RAG1 or RAG2
      knockout backgrounds allows partial, inducible, lymphocyte reconstitution. In
      thymus and peripheral lymphoid organs of reconstituted animals, cells expressing
      CD4 and/or CD8 on their surface, also express CD3 and TCR beta chain. In these
      animals, V(D)J rearrangements are detected in thymus, lymph nodes, and spleen at
      the TRB locus, and in thymus and lymph nodes at the TRD locus. At the TRA locus,
      broken ends at V(D)J recombination signals are detected only in thymus, as are
      reciprocal signal joint products derived from deletional rearrangement. T cell
      reconstitution occurs in these animals whether they are induced in utero during
      development, or shortly after birth. A low level of B cell reconstitution is also
      observed. B220+IgM+ cells are observed in spleen only in induced animals, and
      rearrangements at IGH and IGK loci are detected in bone marrow and spleen. Broken
      signal ends at the IGK locus, are not detected in peripheral lymphoid organs.
      Inducible reconstitution of normal levels of serum immunoglobulin, including
      heavy chain class switch isotype variants is also observed in these animals.
      Further, these transgenes do not appear to interfere with lymphocyte development
      mediated by functionally rearranged TRB chain or IGH chain transgenes in RAG
      deficient animals. These mice provide a unique system for the inducible
      activation of V(D)J recombination and the development of primary lymphocytes.

PMID- 14687939
TI  - A human CR1-like transcript containing sequence for a binding protein for iC4 is
      expressed in hematopoietic and fetal lymphoid tissue.
AB  - Primate immune adherence receptors are erythrocyte complement receptors (E-CR)
      that favorably influence the clearance of circulating immune complexes (IC). The
      human E-CR is the type one complement receptor (CR1), most commonly expressed as
      a 220 kDa protein containing 30 short consensus repeats (SCRs). The chimpanzee E
      CR is a 75 kDa protein composed of eight SCRs, and is encoded by an ortholog of
      human CR1-like (CR1L), a genetic element related to CR1. Human CR1L was
      previously identified from genomic clones that predict exons for seven SCRs, and
      there have been no reports of CR1L expression. The purpose of this study was to
      determine if human CR1L is expressed. Amplification of human bone marrow cDNA
      using primers specific for CR1/CR1L yielded a product similar to chimp CR1L
      encoding sequence. The first 6.5 SCRs matched 100% with the predicted human CR1L
      sequence, while the second half of SCR 7 was homologous to the comparable chimp
      CR1L sequence but with a stop codon. Expression in COS-7 cells yielded a human
      CR1L protein of approximately 50 kDa that exhibited binding specificity for iC4
      but not for iC3. Neither northern nor western blot analysis of human bone marrow
      revealed the presence of the CR1L transcript or protein. However, northern blot
      analysis of various other lymphoid tissue identified a candidate CR1L transcript
      in human fetal liver. PCR amplification of a cDNA panel of human fetal tissue
      confirmed the presence of the CR1L transcript in fetal liver, and to a lesser
      extent in fetal spleen and thymus. Thus, expression of the CR1L transcript
      appears to be limited to hematopoietic and fetal lymphoid tissue.

PMID- 14687940
TI  - The neutralization of pseudorabies virus by anti-alpha-galactocyl natural
      antibody in normal serum.
AB  - Pseudorabies virus (PrV), a member of herpesviridae alphaherpes subfamily, can
      infect human cells in vitro. However, the transmission to Old World primates
      including humans is strongly restricted. In this study, we report the
      neutralizing activity of normal human serum against PrV grown in CPK cells
      derived from pig. PrV grown in all Old World primates-derived cells, which was
      tested in this study, were not neutralized by normal human serum. The virion of
      PrV grown in CPK cells harbored Galalpha1-3Galbeta1-4GlcNAc-R (alpha-gal epitope)
      on its surface, while PrV grown in Vero cells did not. Depletion of antibodies
      reacting to surface antigens of CPK cells negated the neutralization activity of
      human serum. Blockade of anti-alpha-gal antibodies by adding soluble Galalpha1
      3Gal to normal human serum also prevent the inactivation of PrV grown in CPK
      cells. Although normal swine serum did not neutralize PrV grown in CPK cells,
      swine serum supplemented with exogenous anti-alpha-gal antibodies did. These
      results indicate that anti-alpha-gal antibodies in normal human serum contribute
      to the neutralization of PrV. Anti-alpha-gal antibodies in normal human serum may
      prevent transmission of PrV into humans.

PMID- 14687941
TI  - Altered tropism of recombinant bovine adenovirus type-3 expressing chimeric
      fiber.
AB  - Recombinant bovine adenovirus-3 (BAV-3) has been used as a gene delivery vector
      for vaccination of calves. However, its usefulness as a vector for non-bovine
      species is limited due to poor transduction efficiency. To develop BAV-3 based
      vector for non-bovine species, we determined the feasibility of making targeted
      BAV-3 vector by modifying its natural tropism. We constructed a chimeric virus,
      BAV600, in which the knob region of the BAV-3 fiber protein was replaced with
      that from human adenovirus type 5 (HAV-5). Unmodified BAV-3 vector (BAV304) was
      able to transduce and direct the expression of green fluorescent protein (GFP) in
      non-bovine cells, with low efficiency. In contrast, the transduction efficiency
      of BAV600 in these cells was increased by 3-67-fold. Although, expression of
      early and late genes was detected in non-human cells, no progeny virus (BAV600)
      was detected in these cells. Our results suggest that it is possible to develop
      BAV-3 vectors with tropism for non-bovine species.

PMID- 14687942
TI  - Lack of infection of vertebrate cells by the densovirus from the maize worm
      Mythimna loreyi (MlDNV).
AB  - Several densoviruses have been used successfully in biological control of pests
      in the tropics. The densovirus from Mythimna loreyi (MlDNV) could also be an
      important tool in biological control of important pests. However, safety concerns
      remain as previous reports suggested that densoviruses may infect and transform L
      cells (from mouse). In this study, we show using molecular-biology tools that
      neither L nor other vertebrate cells support replication or transcription of
      densovirus, either after infection or after transfection. Quantitative PCR
      indicated no increase of viral DNA due to replication in vertebrate cells, in
      contrast to that in insect LD652 cells. After transfection, both the NS and VP
      mRNAs could be detected in LD652 cells but not in L cells. Moreover, the viral
      genome was excised from the plasmid after transfection of the infectious clone in
      LD652 cells, indicative of viral NS protein production, in contrast to L cells.
      The viral genome was able to integrate in the host chromosome of L cells after
      transfection, but not after infection. However, no viral transcription could be
      detected after integration.

PMID- 14687943
TI  - Differentially expressed genes in HIV-1-infected macrophages following treatment
      with the virus-suppressive immunomodulator murabutide.
AB  - The synthetic immunomodulator murabutide has been found to suppress human
      immunodeficiency virus type-1 (HIV-1) replication, in macrophages, through a
      regulated expression of cellular factors needed at different steps in the virus
      replication cycle. To identify cellular genes implicated in the murabutide
      induced virus inhibition, we have carried out a differential display analysis on
      HIV-1-infected macrophages that were treated, or not, with murabutide. Sequencing
      of the differentially regulated cDNA bands and verification of the
      reproducibility of the murabutide effects, by reverse transcription-polymerase
      chain reaction or by Northern blotting, revealed an up-regulated expression of 21
      genes and a down-regulation of seven others. The murabutide-regulated genes
      encoded proteins implicated in DNA binding, regulation of transcription,
      oxidative stress, metal binding, and other physiological functions. Six of the
      genes corresponded to unassigned/expressed sequence tags with yet unknown
      function. Among the genes which were up-regulated by murabutide and with
      established effects on inhibiting virus transcription, was the octamer binding
      factor 1 (Oct-1). We demonstrate the ability of murabutide to induce enhanced Oct
      1 protein expression and DNA-binding activity in macrophages. Furthermore, our
      findings suggest the potential implication of additional transcription factors
      and metal-binding proteins in mediating the inhibitory effect of murabutide on
      virus transcription.

PMID- 14687944
TI  - Mutational analysis of the predicted secondary RNA structure of the Mason-Pfizer
      monkey virus packaging signal.
AB  - The 5' end of the Mason-Pfizer monkey virus (MPMV) genomic RNA has been predicted
      to fold into a complex stem/loop structure that is thought to play a role in
      specific RNA encapsidation. In this study, we used a set of mutations that either
      abrogated or recreated the first four stem loops predicted within the 5'
      untranslated region (5' UTR) for effects on RNA packaging. Test of these
      mutations in our biological assay revealed that only stem loop 1 (SL1) was
      important for the packaging potential of MPMV, while mutations in none of the
      other stem loops affected packaging significantly. Interestingly, it was the
      primary sequence of SL1 RNA and not its secondary structure that affected
      packaging since compensatory mutations that reformed SL1 were unable to restore
      the packaging efficiency of the retroviral vector. Additionally, our mutational
      analysis reveals that stem loop 4, predicted to be the major packaging
      determinant of MPMV, does not seem to have a significant role in packaging.
      Finally, results of the biological effects of the structural mutations are
      discussed in relation to their effects on the folding potential of the various
      stem loops.

PMID- 14687945
TI  - Inhibition of Dugbe nairovirus replication by human MxA protein.
AB  - Sensitivity to the interferon-induced protein, MxA, has previously been
      demonstrated for viruses belonging to the Orthobunyavirus, Hantavirus and
      Phlebovirus genera of the Bunyaviridae family. We have extended these findings to
      a member of the fourth and remaining genus containing viruses that infect man and
      other animals, the nairovirus Dugbe virus (DUGV). Indirect immunofluorescence
      experiments using VA9 cells (Vero cells permanently transfected with MxA cDNA)
      revealed strongly reduced DUGV antigen expression, suggesting that MxA inhibited
      DUGV replication. Western and Northern blot analyses showed significantly lower
      DUGV nucleocapsid (N) protein expression and DUGV genomic RNA, respectively, in
      the presence of MxA. Viral titres were also reduced by more than two orders of
      magnitude in VA9 cells compared with control VN36 cells. This finding may have
      application to nairovirus therapeutics.

PMID- 14687946
TI  - Detection and characterization of measles virus strains in cases of subacute
      sclerosing panencephalitis in Croatia.
AB  - Two cases of subacute sclerosing panencephalitis (SSPE), diagnosed in Croatia in
      2002, were investigated. The coding regions of the matrix (M), hemagglutinin (H)
      and nucleoprotein (N) genes of measles virus were sequenced following direct RT
      PCR amplification of viral RNA extracted from brain tissue. Phylogenetic analysis
      of the sequences of H and N genes, showed that both strains belonged to genotype
      D6. No vaccine strain was detected although both patients had been previously
      immunized. The comparison of analyzed sequences of two SSPE causative viruses
      with corresponding sequences of D6 genotype and with each other revealed a number
      of mutations in N and H gene sequences. In comparison to the Edmonston reference
      strain, the M gene of the SSPE viruses showed the characteristic biased
      hypermutation and a premature termination codon in one of the patients.

PMID- 14687947
TI  - Studies of structural changes in the M2 proton channel of influenza A virus by
      tryptophan fluorescence.
AB  - Studies of tryptophan fluorescence of purified influenza A virus M2 protein have
      identified two pH-dependent structural changes. (1) An increase in fluorescence
      on reduction of pH from 8 to 6 that involves tryptophan 15 within the N-terminal
      domain of the protein and may be associated with proton activation of the
      channel. (2) Quenching of the fluorescence of tryptophan 41 within the
      transmembrane domain of the channel by histidine 37 below pH 6 which is
      specifically reversed by drugs that block the M2 channel. The pH dependence of
      the latter effect, which monitors changes in the protonation of histidine 37,
      corresponds to that of proton current through the channel and provides evidence
      for the involvement of histidine 37 in proton permeation.

PMID- 14687948
TI  - Hepatitis B virus (HBV) vaccine-induced escape mutants of HBV S gene among
      children from Qidong area, China.
AB  - Hepatitis B virus (HBV) infection is the main factor, which induces
      hepatocellular carcinoma (HCC) in Qidong high-risk area, China. To prevent HBV
      infection is the most important strategy to inhibit the HCC carcinogenesis. A
      large project was performed in Qidong area to protect newborn babies from the HBV
      infection that 80,000 children born between 1984 and 1990 were vaccinated. After
      three times of follow-up studies, 15 screened children were found to have
      symptoms of illness showing persistent elevation of serum glutamic-pyruvic
      transaminase (ALT). From these previously collected data, we found that the ALT
      levels of five vaccinees with negative hepatitis B surface antigen (HBsAg) were
      significantly higher than those of 10 vaccinees with positive HBsAg. Furthermore,
      with the passage of time, the difference of ALT levels between the two groups
      (HBsAg negative and positive groups) diminishes. After cloning and sequencing of
      the HBsAg "a" epitope coding sequences, we found that mutations in "a" epitope
      were correlated with the absence of detectable anti-HBsAg, while no mutations
      were seen in the anti-HBsAg positive infections. We also found that majority of
      point mutations were occurred in the coding sequences of the first loop structure
      in "a" epitope. The structure of double loop conformation in "a" epitope was
      conservative, and important for HBV antigenicity. These changes in a double loop
      conformation would escape neutralization by vaccine-induced antibody.

PMID- 14687949
TI  - Simian retrovirus serogroup 2 constitutive transport element recognizes the
      ribosomal L10-like protein and translocon gamma subunit-like protein in a yeast
      three-hybrid assay.
AB  - The simian retrovirus (SRV) serogroup 2 genome contains a constitutive transport
      element (CTE) within its 3' intergenic region (IR) that mediates the nuclear
      export of unspliced SRV RNA. In a previous report [Virology 264 (1999) 37], CTE
      RNA-protein complexes were detected using UV-crosslinking/sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). To identify these CTE-interacting
      cellular proteins, we utilized yeast three-hybrid interaction approaches using
      the complete IR as bait, modified to eliminate transcriptional termination
      signals recognized by RNA polymerase III, and identified several interactive
      clones from a Hela cell cDNA activation domain (AD) library. UV-crosslinking of
      RNA-protein complexes, using Hela cell extracts and the modified IR bait, were
      conducted prior to library screening, to verify appropriate interaction of CTE
      RNA-protein complexes. Over one million recombinants were screened, and our yeast
      hybrid results indicate that the CTE interacts with several molecules involved in
      cellular translational and translocation machinery, including the ribosomal L10
      like protein and the tranlocon protein gamma subunit-like protein. UV
      crosslinking/immunoblot assays have verified the interaction of the CTE region
      with molecules immunologically reactive to antibodies recognizing the ribosomal
      L10-like protein.

PMID- 14687950
TI  - Cytokine pattern is solely influenced by priming vaccine but immunity and disease
      by both priming and boosting vaccines in mice challenged with respiratory
      syncytial virus.
AB  - Vaccine formulation can influence cytokine and disease patterns in mice following
      respiratory syncytial virus (RSV) challenge. The influence of different live and
      killed dual-vaccine combinations on subsequent immune responses was investigated.
      BALB/c mice received either killed followed by killed (KV/KV), killed followed by
      live (KV/LV), live followed by killed (LV/KV), or live followed by live (LV/LV)
      RSV vaccines intramuscularly. Mouse weight loss, viral replication, cytokine
      expression patterns, immunoglobulin isotype antibody profiles, neutralizing
      antibody responses, and cytotoxicity T lymphocyte (CTL) activities in lungs were
      compared on subsequent live RSV challenge. On challenge, mice vaccinated
      initially with KV and boosted with either KV or LV expressed significantly skewed
      ratios of IL-4 to IFN-gamma mRNA and IgG1 to IgG2a antibody, when compared to
      those vaccinated initially with LV. Low levels of RSV replication were detected
      in lungs of mice vaccinated with KV/KV, KV/LV, and LV/KV, but not in mice
      vaccinated with LV/LV. Mice vaccinated with KV/LV, LV/KV, or LV/LV had RSV
      specific CTL activity in lungs six days after RSV challenge, while no CTL
      activity was detected in KV/KV-vaccinated mice. Mice vaccinated with KV/KV had
      the greatest weight loss, while LV/LV-vaccinated mice resulted in the least. Mice
      vaccinated with either KV/LV or LV/KV had intermediate weight loss after
      challenge. These data indicate that an original antigenic sin-like phenomenon was
      exhibited in cytokine and immunoglobulin isotype responses in mice after
      challenge. T helper (Th)-like immune responses were determined solely by the
      initial vaccination, while weight loss, viral replication, neutralizing antibody
      responses, and CTL activities were also influenced by boosted vaccinations.

PMID- 14687951
TI  - Comparison of serum sensitivities of pseudotype retroviruses produced from newly
      established packaging cell lines of human and feline origins.
AB  - To apply retrovirus vectors for in vivo gene therapy in cats, it is necessary to
      develop vector systems that are not inactivated by cat serum. In this study, the
      retrovirus packaging cell lines 2SC-1 and AHCeB7 were newly established from
      human embryonic kidney (HEK) 293 and feline fibroblastic AH927 cells,
      respectively. Then the sensitivities of pseudotype viruses released from these
      cell lines to fresh sera from humans and cats were compared. Pseudotype viruses
      from the 2SC-1 cells were inactivated efficiently by cat serum but not by human
      serum. Pseudotype viruses from the AHCeB7 cells were also inactivated efficiently
      by human serum, however they were rather resistant to cat serum. When the
      xenoantigenicity of the cell lines was examined by flow cytometry, AH927 cells
      reacted with human serum, however, HEK293 cells did not react with cat serum.
      These results suggested that pseudotype viruses from 2SC-1 cells were inactivated
      by the fresh cat serum in an antibody-independent manner. Chelating experiments
      revealed that certain temperature-sensitive factor(s) other than complements
      might be involved in the inactivation. The usage of feline cells as packaging
      cells is suitable for in vivo gene therapy in cats.

PMID- 14687952
TI  - Antigen presentation by a macrophage-like cell line persistently infected with
      respiratory syncytial virus.
AB  - Severe infection by the human respiratory syncytial virus (RSV) early in life is
      associated with subsequent recurrent airway disease presumably mediated by
      dysregulation of the local immune response. Dysfunction of the immune response
      may be related to impaired macrophage functions. We have previously reported that
      RSV persistence in a macrophage culture (MPhiper) alters Fcgamma receptors
      (FcgammaR)-mediated phagocytosis and the production of pro-inflammatory
      cytokines. Here, we determined whether the ability of macrophages to process and
      present antigens and to stimulate RSV-specific CD8(+) T cells was altered in
      MPhiper. We also examined the level of expression of MHC class I molecules in
      MPhiper and the ability of these cells to present viral antigens to specific T
      lymphocytes. Our results showed that antigen processing and presentation were not
      altered by chronic RSV infection, and suggested that MPhiper were able to
      stimulate RSV-specific CD8(+) T lymphocytes.

PMID- 14687954
TI  - Attempted suicide among entrants to three treatment modalities for heroin
      dependence in the Australian Treatment Outcome Study (ATOS): prevalence and risk
      factors.
AB  - AIMS: To determine the lifetime and recent histories of attempted suicide among
      entrants to treatment for heroin dependence in three treatment modalities and a
      non-treatment comparison group; and to ascertain factors associated with a recent
      history of attempted suicide. DESIGN: Cross-sectional structured interview.
      SETTING: Sydney, Australia. PARTICIPANTS: Six hundred and fifteen current heroin
      users: 201 entering methadone/buprenorphine maintenance (MT), 201 entering
      detoxification (DTX), 133 entering drug free residential rehabilitation (RR) and
      80 not in treatment (NT). FINDINGS: A lifetime history of attempted suicide was
      reported by 34% of subjects, 13% had attempted suicide in the preceding year and
      5% had done so in the preceding month. Females were more likely to have lifetime
      (44% versus 28%) and 12 month (21% versus 9%) suicide attempt histories. The 12
      month prevalence of attempted suicide among treatment groups ranged between 11%
      (MT, NT) and 17% (RR). Factors associated with recent suicide attempts were:
      being an RR entrant, female gender, younger age, less education, more extensive
      polydrug use, benzodiazepine use, recent heroin overdose, Major Depression,
      current suicidal ideation, Borderline Personality Disorder (BPD)and Post
      Traumatic Stress Disorder. CONCLUSIONS: Recent suicidal behaviour is a major
      clinical problem for heroin users, and for females and RR entrants in particular.
      An essential adjunct to treatment for heroin dependence is routine screening for
      depression and suicidal ideation, with the provision of appropriate treatment
      where needed.

PMID- 14687955
TI  - Open-label trial of an injection depot formulation of buprenorphine in opioid
      detoxification.
AB  - Buprenorphine, a partial mu-opioid agonist, has been shown effective for
      treatment of opioid dependence but also has some abuse potential. A novel
      formulation of buprenorphine, using a polymer microcapsule depot sustained
      release technology, has been developed which may offer effective treatment of
      opioid dependence while also minimizing risks of patient noncompliance and
      illicit diversion. This open-label, first-in-human study evaluated the safety and
      pharmacokinetics of a single-dose buprenorphine depot in physically dependent
      opioid abusers. The present study also examined the efficacy of depot
      buprenorphine in suppressing symptoms of opioid withdrawal, attenuating the
      effects of exogenous opioid challenge, and providing clinical detoxification.
      Five opioid-dependent volunteers each received a single subcutaneous depot
      injection containing 58 mg of buprenorphine and were assessed for at least four
      weeks for signs and symptoms of opioid withdrawal, first residentially and then
      as outpatients. Depot buprenorphine appeared to provide effective relief from
      opioid withdrawal, with no participant requiring additional medication for
      withdrawal relief following depot administration. The depot was safe and well
      tolerated, with no significant side effects, signs of intoxication, or
      respiratory depression. In the opioid challenge sessions, depot buprenorphine
      appeared to produce substantial opioid blockade that persisted for 6 weeks post
      depot administration. Results from the present study suggest that depot
      buprenorphine offers significant promise for enhancing the delivery of effective
      opioid agonist treatment while minimizing risk for abuse of the medication.

PMID- 14687956
TI  - Treatment needs associated with pain in substance use disorder patients:
      implications for concurrent treatment.
AB  - Although pain problems are prevalent in substance use disorder (SUD) patients,
      the special treatment needs of SUD patients with pain have not been investigated.
      This study examines the problems and behaviors associated with reported pain
      among veterans treated at eight opioid substitution treatment clinics. Patients
      reporting pain had more severe medical and psychiatric problems and greater
      health care utilization. Pain was associated with an increased propensity for
      misuse of substances with analgesic effects, suggesting that ongoing pain
      contributes to an altered and more severe pattern of drug-seeking behavior.
      Patients without pain rarely abused sedatives or opioid medication, indicating
      that misuse of these substances is unique to co-morbid pain and SUD patients.
      Patients reporting pain did not differ from patients without pain in use of
      heroin, alcohol, cocaine or in injection practices, demonstrating that they are
      truly SUD patients in need of SUD treatment. Pain complicates the treatment of
      SUD and should be addressed as an important co-morbidity during treatment.

PMID- 14687957
TI  - The external validity of results derived from ecstasy users recruited using
      purposive sampling strategies.
AB  - This study sought to compare the patterns and correlates of 'recent' and
      'regular' ecstasy use estimated on the basis of two datasets generated in 2001 in
      New South Wales, Australia, from a probability and a non-probability sample. The
      first was the National Drug Strategy Household Survey (NDSHS), a multistage
      probability sample of the general population; and the second was the Illicit Drug
      Reporting System (IDRS) Party Drugs Module, for which regular ecstasy users were
      recruited using purposive sampling strategies. NDSHS recent ecstasy users (any
      use in the preceding 12 months) were compared on a range of demographic and drug
      use variables to NDSHS regular ecstasy users (at least monthly use in the
      preceding 12 months) and purposively sampled regular ecstasy users (at least
      monthly use in the preceding 6 months). The demographic characteristics of the
      three samples were consistent. Among all three, the mean age was approximately 25
      years, and a majority (60%) of subjects were male, relatively well-educated, and
      currently employed or studying. Patterns of ecstasy use were similar among the
      three samples, although compared to recent users, regular users were likely to
      report more frequent use of ecstasy. All samples were characterised by extensive
      polydrug use, although the two samples of regular ecstasy users reported higher
      rates of other illicit drug use than the sample of recent users. The similarities
      between the demographic and drug use characteristics of the samples are striking,
      and suggest that, at least in NSW, purposive sampling that seeks to draw from a
      wide cross-section of users and to sample a relatively large number of
      individuals, can give rise to samples of ecstasy users that may be considered
      sufficiently representative to reasonably warrant the drawing of inferences
      relating to the entire population. These findings may partially offset concerns
      that purposive samples of ecstasy users are likely to remain a primary source of
      ecstasy-related information.

PMID- 14687958
TI  - Cost-effectiveness analysis of addiction treatment: paradoxes of multiple
      outcomes.
AB  - This paper identifies and illustrates the challenges of conducting cost
      effectiveness analysis (CEA) of addiction treatments given the multiple important
      outcomes of substance abuse treatment (SAT). Potential problems arise because CEA
      is intended primarily for single outcome programs, yet addiction treatment
      results in a variety of outcomes such as reduced drug use and crime and increased
      employment. Methodological principles, empirical examples, and practical advice
      are offered on how to conduct an economic evaluation given multiple outcomes. An
      empirical example is provided to illustrate some of the conflicts in cost
      effectiveness (CE) ratios that may arise across the range of outcomes. The data
      are from the Philadelphia Target Cities quasi-experimental field study of
      standard versus "enhanced" (e.g. case management and added social services) drug
      treatment. Outcomes are derived from of the Addiction Severity Index (ASI), while
      cost data were collected and analyzed using the Drug Abuse Treatment Cost
      Analysis Program (DATCAP). While the results are illustrative only, they indicate
      that cost-effectiveness ratios for each of several different outcomes can produce
      conflicting implications. These findings suggest that multiple outcomes should be
      considered in any economic analysis of addiction treatments because focusing on a
      single outcome may lead to inadequate and possibly incorrect policy inferences.
      However, incorporating multiple outcomes into a CEA of addiction treatment is
      difficult. Cost-benefit analysis (CBA) may be a preferable and more appropriate
      approach in some cases.

PMID- 14687959
TI  - Long-term voluntary D-amphetamine consumption and behavioral predictors for
      subsequent D-amphetamine addiction in rats.
AB  - Flexibility of drug taking is characteristic for "controlled" drug consumption
      whereas addiction is reflected by inflexibility and persistent high risk to
      relapse. Male Wistar rats (N = 12) that were given a continuous free choice
      between water and D-amphetamine solutions for 16 weeks, revealed a moderate and
      flexible pattern of D-amphetamine intake when tested again after 36 weeks of drug
      deprivation. A second group of rats had the same choice between water and D
      amphetamine for 42 weeks. In the retest after abstinence, six out of 12 rats
      showed a moderate and flexible pattern of intake whereas the other animals
      revealed an excessively high and inflexible D-amphetamine consumption. They took
      high doses despite an adverse bitter taste of the drug solutions caused by
      addition of quinine. After 39 weeks of moderate D-amphetamine intake in the long
      term period exactly the same animals had spontaneously and suddenly increased
      their D-amphetamine consumption. In a retrospective view, the later inflexible D
      amphetamine consumers had already shown differences to their flexible
      conspecifics before their first drug access. During "tetradic" encounter tests
      the later "inflexible" animals were more interested in non-social stimuli than
      the later "flexible" ones. The results are discussed in respect to predisposition
      factors that might facilitate or inhibit the development of loss of control over
      drug intake.

PMID- 14687960
TI  - Social network correlates of self-reported non-fatal overdose.
AB  - The leading cause of death among heroin users is drug overdose. The present study
      examined the relationship between history of self-reported drug overdoses and
      social network characteristics among cocaine and opiate users. Data were from
      cross-sectional surveys administered from March 2001 through February 2003 as
      part of follow-up of an experimental network oriented HIV prevention
      intervention. A total of 838 participants with histories of cocaine and opiate
      use completed the survey. Several social network variables were found to be
      significantly associated with drug overdose in the prior 2 years, including
      larger number of network members who were injection drug users and a larger
      number of conflictual ties among the network members. Even after controlling for
      age, gender, frequency of injection drug and alcohol use, and health status,
      network variables continued to have a strong association with history of recent
      overdose. These data suggest that large drug networks should be targeted for drug
      overdose prevention interventions.

PMID- 14687961
TI  - Hepatitis B virus infection and vaccination among young injection and non
      injection drug users: missed opportunities to prevent infection.
AB  - INTRODUCTION: We examined correlates of HBV infection and vaccination and the
      missed vaccination opportunities among young injection drug users (IDUs) and non
      injection drug users (NIDUs). METHODS: Two hundred IDUs and 124 NIDUs aged 15-30
      years were studied. Demographics, drug use and sexual behaviors, and health and
      incarceration history data were collected. Serology was conducted for antibodies
      to HBV-core antigen (anti-HBc) and HBV-surface antigen (anti-HBs). Presence of
      anti-HBc indicated past HBV infection; presence of anti-HBs alone indicated past
      vaccination. RESULTS: More IDUs had been infected with HBV in the past than NIDUs
      (37% versus 19%, P = 0.001). Among male and female IDUs, injection drug use
      behaviors were significantly associated with past infection. For female IDUs,
      being African-American and trading sex were also associated with previous
      infection. Among NIDUs, being female and longer time since sexual debut were
      associated with past infection. Overall, 11% were vaccinated (10% IDU versus 14%
      NIDU, P = 0.30). Younger age and drug treatment history were associated with
      vaccination. Most susceptibles (84%) experienced at least one missed opportunity
      for vaccination. CONCLUSION: Young drug users remain at high risk for HBV
      infection. Vaccination rates remain low despite multiple opportunities for
      vaccination. An integrated HBV immunization effort should be coordinated among
      venues frequented by young drug users.

PMID- 14687962
TI  - Impaired performance in a test of decision-making by opiate-dependent tobacco
      smokers.
AB  - This study tested whether opiate dependence, tobacco smoking, or their
      combination accompanied impaired performance on the gambling task (GT), which
      tests decision-making. GT previously detected impairments in patients with
      lesions of the ventromedial prefrontal cortex and in substance abusers. Four
      groups were matched on demographic characteristics and intelligence: methadone
      maintained smokers (n = 9) and nonsmokers (n = 9), and control (i.e., not opiate
      dependent) smokers (n = 9) and nonsmokers (n = 10). The Wisconsin Card Sorting
      Task (WCST) was administered to test whether differences in GT performance
      reflected generalized deficits in prefrontal cortical function. While there were
      no significant group differences on the WCST, groups differed significantly on GT
      performance (F(3,31) = 2.95, P = 0.048), controlling for depressive symptom
      ratings and childhood attention deficit hyperactivity disorder. Methadone
      maintained smokers (but not nonsmokers) performed more poorly than either of the
      two control groups (P = 0.007 versus smokers; P = 0.024 versus nonsmokers). In a
      planned analysis of methadone-maintained subjects, smokers scored more poorly on
      GT than nonsmokers (F(1,18) = 5.64, P = 0.032) and had more treatment failures
      (67% heroin use during the last 30 days versus 20%). The findings suggest that
      among opiate-dependent individuals, tobacco smoking may be a marker for a more
      severe form of substance abuse disorder, reflecting impaired decision-making, as
      modeled by GT.

PMID- 14687963
TI  - Psychiatric disorders and attempted suicide among adolescents with substance use
      disorders.
AB  - OBJECTIVE: To determine the effects of psychiatric disorders on attempted suicide
      among adolescents with substance use disorders (SUD). METHODS: Age of onset for
      psychiatric disorders, age of first suicide attempt, and the relationship of
      psychiatric disorder with attempted suicide were investigated in a sample of 503
      adolescents with DSM-IV defined SUD (age range: 12.2-19.0 years). RESULTS: Males
      who attempted suicide had a significantly earlier onset of alcohol use disorders
      (AUD) and significantly more mood, AUD, and disruptive behavior disorder symptoms
      compared to non-attempting males. Females who attempted suicide had a
      significantly earlier onset and higher counts of mood disorders and SUD symptoms
      compared to non-attempting females. Hazard analysis revealed that mood disorders
      represent the highest psychiatric risk for attempted suicide in both the genders.
      Attention deficit-hyperactivity disorder (ADHD) increased the risk for attempted
      suicide among males. The interaction of mood disorder and AUD increased the risk
      for attempted suicide among females. CONCLUSIONS: Clinicians should closely
      monitor SUD adolescents for suicide risk and be aware of gender differences for
      suicidal behavior based on course and severity of psychiatric disorder in this
      population.

PMID- 14687964
TI  - An evaluation of workshop training in motivational interviewing for addiction and
      mental health clinicians.
AB  - We evaluated a 2-day training workshop on motivational interviewing (MI) for
      addiction and mental health clinicians (n = 22). Clinicians completed the helpful
      responses questionnaire (HRQ) and taped interactions with a standardized patient
      (SP). Independent, blinded coders rated the tapes using the motivational
      interviewing skills code (MISC). Post-training assessment showed significant
      increase on the HRQ and two of four MISC summary scores for SP interviews. At 2
      month follow-up, means of the HRQ and two MISC summary scores remained higher
      than baseline, but declined from post-training. Some MI skills improved to a
      greater degree than others, and a subset of clinicians (> 40%) showed continued
      improvement at follow-up. Results were consistent across interviews with
      different SPs, supporting the use of this assessment method. Findings highlight
      the need for additional research on the use of standardized patients, alternative
      assessment techniques, and effective methods of technology transfer for MI skill
      acquisition and retention.

PMID- 14687965
TI  - Drug hypersensitivity reactions in skin: understanding mechanisms and the
      development of diagnostic and predictive tests.
AB  - Cutaneous manifestations of drug hypersensitivity can be serious and potentially
      life threatening and may prevent effective drug therapy. T cells play an
      important role in the pathology of drug hypersensitivity reactions. Classical
      studies suggest that T-cell activation requires drug bioactivation, covalent
      binding to protein and antigen processing to stimulate an immune response. Recent
      studies have shown that drugs can also be presented to T cells in the absence of
      antigen processing and drug metabolism. In this article, sulfamethoxazole is used
      as a paradigm to describe the chemical mechanisms involved in the initiation and
      maintenance of an aberrant drug antigen specific T-cell response. Presentation of
      the same drug to different individuals can cause a variety of skin diseases. Such
      reactions have been classified according to the phenotype and functionality of
      the T-cell response. This review summarises the different forms of cutaneous
      hypersensitivity reactions and describes how T-cell clones generated from
      hypersensitive patients have been used to study the cellular mechanisms of
      anticonvulsant hypersensitivity. Potential uses of in vitro cell culture assays
      for patient diagnosis and drug evaluation are also discussed.

PMID- 14687967
TI  - Large scale gene expression profiling of metabolic shift of mammalian cells in
      culture.
AB  - The metabolic state of hybridoma cells in continuous culture varies with the
      cultivation condition from which the culture is initiated. At a metabolically
      shifted state, cells have markedly reduced glucose and other nutrient consumption
      and lactate production as compared to cells in batch culture or in continuous
      culture without a metabolic shift. Taking a combined genomics and proteomics
      approach, we investigated the molecular mechanism of metabolic shift. Cells from
      continuous cultures at two different steady states with a glucose consumption to
      lactate production molar ratio (DeltaL/DeltaG) of 0.08 and 1.4 were studied.
      Affymetrix GeneChips as well as cDNA microarrays were employed to identify
      differentially expressed mRNA transcripts, and the differentially expressed
      proteins were identified using the 2D gel electrophoresis-mass spectrometry
      approach. The decrease in glucose metabolism upon metabolic shift is accompanied
      by a decrease in gene expression of a number of genes involved in its metabolism.
      However, the number of genes differentially expressed and the extent of
      differential expression upon metabolic shift are relatively moderate. The change
      in the expression of metabolic genes at the transcriptional level was confirmed
      by real time PCR. The results suggest that metabolic shift is a combined effect
      of both biochemical events at reaction level and gene expression at transcription
      and translation level. This approach of integrating transcriptional profiling,
      proteomic techniques and biochemical analysis provides a more global view of the
      metabolism of mammalian cells in culture.

PMID- 14687968
TI  - Systematic comparison of the fidelity of aRNA, mRNA and T-RNA on gene expression
      profiling using cDNA microarray.
AB  - In cDNA microarray technology, there are three main reverse transcription based
      RNA labeling methods, using total RNA (T-RNA), mRNA, and amplified antisense RNA
      (aRNA), respectively. However, despite the common use of the three types of RNAs,
      limited data are available regarding their differences and concordances. In this
      report, we compared the three methods through two sets of self-comparison
      experiments using the same RNA sample in all cases. Within each method, duplicate
      hybridizations are highly reproducible with low biases, which are randomly
      produced. When combining different RNAs within a single array, correlation
      coefficients between the two channels are rather low, while the discrepancies are
      persistent. Furthermore, the fidelity of aRNA and mRNA microarrays in the
      expression profile study shows no significant difference with standard T-RNA
      based labeling methods. These results suggest that some RNA abundance are
      selectively changed during aRNA amplification/mRNA purification processes, but it
      will not affect the gene expression ratio of the two samples if the same type RNA
      are used. Therefore all three types of RNAs can be used in expression profiling
      analysis as long as the test and reference samples are generated by identical
      method within single study.

PMID- 14687969
TI  - Critical variations of conjugational DNA transfer into secondary metabolite
      multiproducing Sorangium cellulosum strains So ce12 and So ce56: development of a
      mariner-based transposon mutagenesis system.
AB  - Myxobacteria increasingly gain attention as a source of bioactive natural
      products. The genus Sorangium produces almost half of the secondary metabolites
      isolated from these microorganisms. Nevertheless, genetic systems for Sorangium
      strains are poorly developed, which makes the identification of the genes
      directing natural product biosynthesis difficult. Using biparental and
      triparental mating, we have developed methodologies for DNA transfer from
      Escherichia coli via conjugation for the genome sequencing model strain So ce56
      and the secondary metabolite multiproducing strain So ce12. The conjugation
      protocol developed for strain So ce56 is not applicable to other Sorangium
      strains. Crucial points for the conjugation are the ratio of E. coli and
      Sorangium cellulosum cells, the choice of liquid or solid medium, the time used
      for the conjugation process and antibiotic selection in liquid medium prior to
      the plating of cells. A mariner-based transposon containing a hygromycin
      resistance gene was generated and used as the selectable marker for S.
      cellulosum. The transposon randomly integrates into the chromosome of both
      strains. As a proof of principle, S. cellulosum So ce12 transposon mutants were
      screened using an overlay assay to target the chivosazole biosynthetic gene
      cluster.

PMID- 14687970
TI  - Polyhydroxybutyrate synthesis in transgenic flax.
AB  - Flax (Linum usitatissimum L.) is an annual plant species widely cultivated in
      temperate climates for bast fibres and linseed oil. Apart from traditional
      textile use, the fibres are fast becoming an integral part of new composite
      materials utilized in automobile and constructive industry. Especially attractive
      for environmental safety demands are biodegradable and renewable biocomposities
      based on polyhydroxybutyrate (PHB) polymer as a matrix and reinforced with the
      flax fibres. Manufacturing of PHB by bacteria fermentation is however
      substantially more expansive as compared to technologies producing conventional
      plastics. We report for the first time generation of transgenic plants which
      produce both components of flax/PHB composites, i.e. the fibres and the
      thermoplastic matrix in the same plant organ of a crop. The flax (cv. Nike)
      plants were transformed using constructs bearing either single cDNA, encoding the
      beta-ketothiolase enzyme (C plants), or all three of the genes necessary for poly
      beta-hydroxybutyrate (PHB) synthesis (M plants). Both constructs contained a
      plastidial targeting sequence. The amount of PHB produced by the transgenic
      plants was up to over 70-fold higher than in wild-type plants, when analysed
      using the gas chromatography/mass spectrometry (GC-MS method). The PHB
      accumulation in plastids caused change both in their shape and size. The use of a
      stem-specific promoter for transgene expression protected the transgenic plant
      from growth retardation and also provided higher PHB synthesis than in the case
      of constructs governed by the 35S CaMV constitutive promoter. None toxic effects
      that could lead to stunted growth or the loss of fertility were observed, when 14
      3-3 promoter was used as the stem-specific. Significant modifications in stem
      mechanical properties were accompanied to the PHB accumulation in growing cell of
      fibres in the transgenic plants. The Young's modulus E, the average measure of
      stem tissues resistance to tensile loads increased up to twice in M plants as
      compared to a single gene transformed ones. However, a wide range of E values,
      from 24.1 to 54.4 MPa, was observed in dependence of tested strain. Potential
      commercial significance of the genetic manipulation approach enabling synthesis
      of thermoplastic in crops cultivated for fibres is discussed.

PMID- 14687971
TI  - Scale-up of virus-like particles production: effects of sparging, agitation and
      bioreactor scale on cell growth, infection kinetics and productivity.
AB  - The baculovirus-insect cells expression system was used for the production of
      self-forming Porcine parvovirus (PPV) like particles (virus-like particles, VLPs)
      in serum-free medium. At 2l bioreactor scale an efficient production was achieved
      by infecting the culture at a concentration of 1.5 x 10(6)cells/ml using a low
      multiplicity of infection of 0.05 pfu per cell. In a continuous bioreactor, it
      was shown that the uninfected insect cells were not sensitive to local shear
      stress values up to 2.25 N/m2 at high Reynolds numbers (1.5 x 10(4)) in sparging
      conditions. Uninfected insect cells can be grown at scaled-up bioreactor at high
      agitation and sparging rates as long as vortex formation is avoided and bubble
      entrapment is minimized. An efficient process scale-up to 25 l bioreactor was
      made using constant shear stress criteria for scale-up. The kinetics of
      baculovirus infection at low multiplicity of infection, either at different cell
      concentration or at different scales, are very reproducible, despite the
      different turbulence conditions present in the bioreactor milieu. The results
      suggest that the infection kinetics is controlled by the rate of baculovirus-cell
      receptor attachment and is independent of the bioreactor hydrodynamic conditions.
      Furthermore, the achieved specific and volumetric productivities were higher at
      the 25 l scale when compared to the smaller scale bioreactor. Different rates of
      cell lysis after infection were observed and seem to fully explain both the shift
      in optimal harvest time and the increase in cell specific productivity. The
      results emphasize the importance of integrated strategies and engineering
      concepts in process development at bioreactor stage with the baculovirus insect
      cell system.

PMID- 14687972
TI  - Adsorption of Trichoderma reesei CBH I and EG II and their catalytic domains on
      steam pretreated softwood and isolated lignin.
AB  - The presence of lignin has shown to play an important role in the enzymatic
      degradation of softwood. The adsorption of enzymes, and their constituent
      functional domains on the lignocellulosic material is of key importance to
      fundamental knowledge of enzymatic hydrolysis. In this study, we compared the
      adsorption of two purified cellulases from Trichoderma reesei, CBH I (Cel7A) and
      EG II (Cel5A) and their catalytic domains on steam pretreated softwood (SPS) and
      lignin using tritium labeled enzymes. Both CBH I and its catalytic domain
      exhibited a higher affinity to SPS than EG II or its catalytic domain. Removal of
      cellulose binding domain decreased markedly the binding efficiency. Significant
      amounts of CBH I and EG II also bound to isolated lignin. Surprisingly, the
      catalytic domains of the two enzymes of T. reesei differed essentially in the
      adsorption to isolated lignin. The catalytic domain of EG II was able to adsorb
      to alkaline isolated lignin with a high affinity, whereas the catalytic domain of
      CBH I did not adsorb to any of the lignins tested. The results indicate that the
      cellulose binding domain has a significant role in the unspecific binding of
      cellulases to lignin.

PMID- 14687973
TI  - Diketone cleaving enzyme Dke1 production by Acinetobacter johnsonii--optimization
      of fermentation conditions.
AB  - The main objective of this work was the optimization of the production of the
      novel dioxygenase diketone cleaving enzyme (Dke1) from Acinetobacter johnsonii.
      Acetylacetone was used as an inducer for enzyme production. In the first step,
      the growth medium was optimized by using screening designs for finding the
      optimal carbon and nitrogen source. In the second step, a genetic algorithm was
      used to optimize the concentrations of all medium components. After six
      generations the stopping criterion was reached and a growth medium was obtained
      which produced sixteen times more enzyme than the starting medium. In the next
      step, an addition profile for the inducer acetylacetone was developed to further
      increase enzyme production by using a genetic algorithm. In this case, after four
      generations the stopping criterion was fulfilled. By using the obtained optimal
      addition profile Dke1 activity was enhanced from 826 to 2584Ul(-1). In comparison
      to the starting conditions activity could even be increased by a factor of 50.

PMID- 14687974
TI  - A flexible peptide linker enhances the immunoreactivity of two copies HBsAg preS1
      (21-47) fusion protein.
AB  - PreS1 (21-47) region of HBV large surface protein is hepatocyte receptor binding
      site and the anti-preS1 (21-47) antibody possesses the virus-neutralizing
      activity and protective effect. It is important to obtain the peptide with higher
      immunoreactivity on a large scale for detecting the anti-preS1 (21-47) antibody
      in the sera from HBV infected patients and future vaccine recipients. The
      expression vector pGEX SLS, which expressed two copies of the preS1 (21-47)
      peptide connected by a flexible linker (Gly4Ser3) fused to glutathione S
      transferase (GST), was constructed. The fusion protein, named GST-SLS, was highly
      expressed in E. coli and purified by affinity chromatography. Ninety milligrams
      purified protein can be obtained from 1l of culture. The data in ELISA analysis
      showed that the immunoreactivity of GST-SLS was enhanced significantly in
      comparison with GST-S II, a GST fusion protein with two copies preS1 (21-47)
      linked directly; GST-S I, another GST fusion protein with one copy preS1 (21-47)
      and preS1 (21-47) synthesized peptide. In addition, GST-SLS has been tried to use
      in detecting anti-preS1 (21-47) antibody in the sera from HBV infected patients
      and a satisfied result was gained. Therefore, GST-SLS may have potential to be
      developed into a new kit for diagnosis and prognosis of hepatitis B (HB)
      patients.

PMID- 14687975
TI  - Genotoxicant induced DNA damage and repair in early and late developmental stages
      of the grass shrimp Paleomonetes pugio embryo as measured by the comet assay.
AB  - In this study, data are presented which link frequency of DNA strand breaks and
      repair capability to developmental stage. Stages 4 and 7 embryos of the grass
      shrimp (Palaemonetes pugio) were exposed to various concentrations of
      benzo[alpha]pyrene (BalphaP), Cr(VI) and hydrogen peroxide. Following exposure,
      responses were measured as changes in hatching rates and DNA strand breaks (using
      the comet assay). The comet assay was modified by treatment of isolated nuclei
      with endonucleases which cleave DNA at oxidative lesions in DNA prior to
      electrophoresis. DNA repair was followed by transfer of toxicant exposed embryos
      to clean water and periodic determination of strand breaks. DNA strand breaks
      were higher in stage 7 embryos than in stage 4 embryos after exposure to the same
      concentration of different genotoxicants. However, when samples were treated with
      endonucleases to measure oxidative lesions, the total amount of DNA damage
      between stages 4 and 7 were similar. After toxicant exposure and transfer to
      clean water, DNA strand breaks in stage 7 embryos returned to background levels
      more rapidly than in stage 4 embryos. Similarly, samples treated with
      endonucleases during DNA repair studies showed that oxidative lesions were
      repaired more rapidly in stage 7 than in stage 4. These findings suggest that
      because of rapid DNA repair in late embryo stages that early embryo stages are
      more likely to have developmental effects after genotoxicant exposure.

PMID- 14687976
TI  - Mechanistic basis for estrogenic effects in fathead minnow (Pimephales promelas)
      following exposure to the androgen 17alpha-methyltestosterone: conversion of
      17alpha-methyltestosterone to 17alpha-methylestradiol.
AB  - Exposure of adult fathead minnows (Pimephales promelas) to the androgen 17alpha
      methyltestosterone (MT) produces both androgenic and estrogenic effects,
      manifested as nuptial tubercle formation in females, and vitellogenin production
      in males and females, respectively. The present study was conducted to determine
      if the unanticipated estrogenic effects are produced by conversion of MT via
      aromatase activity to 17alpha-methylestradiol (ME2). Aromatase activity at the
      end of a 7-day waterborne MT exposure (20, 200microg/l) was significantly
      decreased in ovarian microsomes and brain homogenates from exposed fish, to about
      30-50% of control activity. Although aromatase activity was decreased by 7 days,
      it is possible that the conversion of MT to ME2 occurred soon after initial
      exposure. In support of this, ME2 was detected in plasma samples of the fish
      following the 7-day exposure, confirming their ability convert the androgen MT to
      the estrogen ME2. The concentration of ME2 in plasma was within the range of
      plasma 17ss-estradiol (E2) found in control female fathead minnows (4-5ng/ml).
      These results, in conjunction with competitive binding assays that indicate ME2
      binds to the fathead minnow estrogen receptor with a relative binding affinity of
      68.3% of E2, support the hypothesis that aromatization of MT to ME2 contributes
      to the estrogenic effects in fathead minnows following exposure to this androgen.

PMID- 14687977
TI  - Histological analysis of acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) in zebrafish.
AB  - Previous studies have demonstrated that acute exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) by injection leads to inhibition of caudal fin
      regeneration in zebrafish. Since the TCDD exposure in these studies is systemic,
      it is possible that pathology in organs other than the fin could result in
      inhibition of fin regeneration. Therefore, histopathology of adult zebrafish
      (Danio rerio) organs was characterized following abdominal cavity injection of a
      TCDD dose (70ng/g). The most pronounced histopathologic changes 5 days post
      injection included lipidosis and hypertrophy of liver hepatocytes and hypertrophy
      of gill lamellae. Effects of TCDD exposure on immunolocalization of the zebrafish
      aryl hydrocarbon receptor nuclear translocator (ARNT2), the heterodimer partner
      of the aryl hydrocarbon receptor (AHR2), and an AHR regulated gene cytochrome
      P450 1A (CYP1A) was also determined. ARNT2 was immunolocalized to the
      gastrointestinal tract, gill lamellae, kidney, ventricle of the heart, caudal
      fin, brain and liver of zebrafish. TCDD exposure had no measurable effect on
      ARNT2 abundance or localization. CYP1A was immunolocalized in TCDD exposed fish
      as a biomarker for cells with an activated AHR pathway. CYP1A was not detected in
      any tissue from vehicle exposed fish. Significant TCDD-dependent induction of
      CYP1A was detected in the proximal tubules of the kidney, in liver hepatocytes
      and in the gastrointestinal tract of TCDD exposed fish. Significant but lower
      TCDD-dependent CYP1A expression was evident in the gill, caudal fin and ventricle
      of the heart. Overall, TCDD exposure in adult zebrafish leads to histopathology
      similar to that reported in other fish species, and it appears unlikely that the
      histopathology in these organs completely explains the inhibition of fin
      regeneration.

PMID- 14687978
TI  - Trophic transfer and in vivo immunotoxicological effects of tributyltin (TBT) in
      polar seastar Leptasterias polaris.
AB  - This study investigated the potential in vivo immunotoxic effects of tributyltin
      (TBT) on amoebocytes of 6-armed seastar Leptasterias polaris. Tested animals were
      contaminated by trophic transfer via alive contaminated prey consisting of blue
      mussels (3microg TBT g(-1) wet weight (WW) tissue) exposed to seawater containing
      dissolved TBT. Four biomarkers of immunotoxicological effects were monitored over
      45 days at different sampling times (9, 24, 48 and 72h, 11, 18, 25, 32 and 45
      days): amoebocytes count (AC), cell viability using Trypan blue exclusion test,
      phagocytic activity (PA) using a suspension of dead bacteria labelled with
      fluorescein isothiocyanate (FITC) and injected directly in the coelomic fluid of
      the animals, and lysosomal integrity (LI) using the neutral red (NR) retention
      test. Data showed that TBT and its metabolites (DBT and MBT) bioaccumulated
      preferentially in pyloric caeca, whereas gonads contained only small quantities.
      Despite the differences in exposure periods to the contaminated diet and in
      burdens of butyltins (BTs) ingested by the various contaminated groups, there
      were no significant differences in body burdens of BTs. Only 6.2+/-2.0% of total
      ingested BTs were retained in soft tissues of seastars. Even if butyltins were
      not detected in the coelomic fluid (CF), their detrimental effects have been
      detected in the phagocytic activity of amoebocytes and their lysosomal retention
      of neutral red, but no effects were observed on amoebocytes count and their
      viability. These results show that seastar L. polaris possesses adequate
      mechanisms to depurate ingested TBT without supporting major disturbances of its
      immune defence system. By their ability to digest whole contaminated prey and
      eliminate only dissolved metabolites, L. polaris and other seastars with the same
      preying mode could play a role of "recycling organisms" in coastal environments
      where toxicants, such as butyltins and other metallic species are accumulated by
      bivalves and particularly blue mussels.

PMID- 14687979
TI  - The time course of silver accumulation in rainbow trout during static exposure to
      silver nitrate: physiological regulation or an artifact of the exposure
      conditions?
AB  - The pattern of gill silver accumulation in rainbow trout during waterborne silver
      exposure has been reported to be unusual, reaching a peak in the first few hours
      of silver exposure followed by a marked decline with continued exposure. The
      potential causes of the pattern were investigated. Rainbow trout (1-5g) were
      exposed in a static system to 110mAg labeled AgNO(3) at a total concentration of
      1.92microg Agl(-1) for 24h in synthetic soft water. Periodically throughout the
      exposure, gill and body 110mAg accumulation, gill and body 24Na uptake (from
      which whole body Na(+) uptake was calculated), gill Na(+)K(+)-ATPase activity,
      plus water silver (total and dissolved), Cl(-) and total organic carbon (TOC)
      concentrations were measured. Gill silver levels rapidly increased, peaked at 3h
      of exposure and then decreased until a plateau was reached at 12h of exposure.
      Body (minus gills) silver levels increased steadily over the exposure period
      until 18h of exposure. Whole body Na(+) uptake decreased, was maximally inhibited
      by 3h of exposure but recovered by 12h despite continued silver exposure. Gill
      Na(+)K(+)-ATPase activity was not inhibited until 5h of exposure. The water
      dissolved silver concentration declined by approximately 70% over the 24h
      exposure period and the TOC content of the water increased over three-fold during
      the first 2h of exposure. There was a decrease in the calculated contribution of
      Ag(+) (from 20.9 to 2.5%) and an increase in the calculated contribution of Ag
      TOC complexes (from 77 to 97.3%) to the total water silver concentration over the
      first 2h of exposure. Apical silver uptake into the gills decreased over the
      initial 2.5h of exposure while basolateral silver export out of the gills to the
      body remained constant throughout the exposure. The results of this study suggest
      that: (1) physiological regulation of silver movement may explain the pattern of
      gill silver accumulation observed in rainbow trout, although not by a mechanism
      coupled to Na(+)K(+)-ATPase inhibition as originally proposed; (2) alternatively
      or additionally, a decreased bioavailability of silver, due to the static
      exposure conditions, may explain the pattern of gill accumulation; (3) the early
      inhibition of whole body Na(+) uptake observed during silver exposure occurs via
      a mechanism other than Na(+)K(+)-ATPase inhibition; and (4) gill silver
      accumulation may be an appropriate endpoint for biotic ligand modeling.

PMID- 14687980
TI  - Changes in cadmium accumulation as a mechanism for cadmium resistance in the
      least killifish Heterandria formosa.
AB  - Evolution of resistance to heavy metals may involve complex changes at the
      physiological level. We report here on research into changes in cadmium uptake
      and accumulation as mechanisms underlying the increased resistance to Cd in
      laboratory lines of the least killifish, Heterandria formosa. We compared Cd
      accumulation between three control lines and three lines selected successfully
      for an increased Cd-resistance. Individuals of the Cd-adapted lines had a lower
      short-term (2h) uptake of Cd than those of the control lines. A time-series
      experiment showed that selection-line fish had a lower rate of Cd accumulation
      than fish from the control lines during the first 14h of exposure to 6mg/l of Cd.
      At the 14h time point, Cd accumulation in the control-line fish approached lethal
      levels, while Cd levels in selection-line fish from this point on increased at a
      slower rate than in the initial 14h. Overall, the relatively small changes in
      uptake and accumulation patterns caused lethal body burdens in the fish from the
      selection lines to be reached at more than twice the exposure duration at which
      this occurred in fish from the control lines. Lethal Cd levels appeared to be the
      same in control- and selection-line fish. Our results suggest that reduced uptake
      and accumulation of Cd accounted for approximately two-third of the increased
      resistance in the Cd-adapted lines.

PMID- 14687981
TI  - Carbofuran insecticide induced biochemical alterations in liver and muscle
      tissues of the fish Clarias batrachus (linn) and recovery response.
AB  - The effect of carbofuran insecticide on certain metabolites and enzymes of
      protein and carbohydrate metabolism was evaluated in liver and muscle tissues of
      the freshwater fish, Clarias batrachus during exposure and following cessation of
      exposure. Thirty-six fish were exposed to 7.66mg of carbofuran/l for 6 days.
      After 6 days, 18 fish were transferred into carbofuran-free water for 6 days
      (recovery period) in order to study the recovery response. Eighteen fish were
      kept in clean water as controls. Liver and muscle tissues were isolated from
      exposed, recovery and control fish at the end of 1, 3 and 6 days in each
      condition, and used for the estimation of protein, amino acids, ammonia,
      glycogen, aminotransaminases, glycogen phosphorylase (a and ab) and glutamate
      dehydrogenase. Total protein showed a delayed decrease in liver and muscle
      tissues but recovered by the end of the recovery period. Free amino acid content
      was affected little in liver, but was elevated in muscle, and ammonia levels were
      elevated in both tissues throughout the exposure period, and ammonia levels in
      liver remained elevated during recovery. Glycogen content of liver declined
      substantially, and rebounded after transfer of fish into clean water. The
      activity levels of alanine aminotransaminase, aspartate aminotransaminase,
      glutamate dehydrogenase and glycogen phosphorylase a were found to increase in
      both tissues during the exposure period. The glycogen phosphorylase ab activity
      in liver was suppressed on exposure to carbofuran. The enzymes exhibited
      different recovery pattern in liver and muscle tissues of C. batrachus. The
      patterns of effect of carbofuran on intermediary metabolism suggest avenues to
      determine the mechanisms by which such effects occur.

PMID- 14687982
TI  - The effect of atrazine on Atlantic salmon (Salmo salar) smolts in fresh water and
      after sea water transfer.
AB  - Groups of Atlantic salmon smolts were exposed to low levels of the pesticide
      atrazine (2-chloro-4-ethylamino-6-isopropylamino-S-triazine) (0-22.7microgl(-1))
      in fresh water and the physiological effects of exposure were measured. Further
      experiments exposed salmon smolts to similar levels of atrazine in fresh water,
      and then exposed them to full strength sea water. Atrazine in fresh water
      resulted in a significant reduction in gill Na(+)K(+)ATPase activity at
      concentrations of 2.0, 5.0 and 10.0microgl(-1). There were few other
      physiological changes in the smolts except for slightly elevated plasma cortisol
      concentrations and monovalent ion concentrations at and above 5.0microgl(-1).
      However, a sea water challenge caused mortalities in smolts that had been pre
      exposed to atrazine in fresh water at concentrations of 1.0, 2.0, 5.0, 10.0 and
      22.7microgl(-1). Moreover, surviving fish showed signs of major physiological
      stress: elevated plasma cortisol, thyroxine, osmolality, and monovalent ion
      concentrations. However, atrazine exposure had no effect on muscle or plasma
      water contents. The data suggests that exposure of salmon smolts to atrazine in
      fresh water may compromise their physiological capabilities to survive in saline
      conditions.

PMID- 14687983
TI  - Synaptic plasticity and cell cycle activation in neurons are alternative effector
      pathways: the 'Dr. Jekyll and Mr. Hyde concept' of Alzheimer's disease or the yin
      and yang of neuroplasticity.
AB  - Mental actions are based on the dynamic organization of neuronal networks. In
      particular, phylogenetically young brain areas (e.g., cortical associative
      circuits) involved in the realization of higher brain functions are continuously
      re-adjusted to meet environmental demands. The mechanisms of synaptic plasticity,
      i.e., of structural stabilization and labilization underlying a life-long
      synaptic remodelling, are largely based on external morphoregulatory cues and
      internal signalling pathways that non-neuronal cells have phylogenetically
      acquired to sense their relationship to the local neighbourhood and to control
      after development is completed proliferation and differentiation in the process
      of tissue repair and regeneration. After having withdrawn from the cell cycle,
      differentiated neurons are, thus, able to use molecular mechanisms primarily
      developed to control proliferation alternatively to control synaptic plasticity.
      The existence of these alternative effector pathways within a neuron puts it at
      risk to erroneously convert signals derived from plastic synaptic changes into
      positional cues that will activate the cell cycle. This cell cycle activation
      potentially links synaptic plasticity to cell death. Preventing cell cycle
      activation by locking neurons in a differentiated but still highly plastic
      phenotype will, thus, be crucial to prevent neurodegeneration.

PMID- 14687984
TI  - Role of semaphorins in the adult nervous system.
AB  - In the developing nervous system, extending axons are directed towards their
      appropriate targets by a myriad of attractive and repulsive guidance cues. Work
      in the past decade has significantly advanced our understanding of these
      molecules and has made it increasingly clear that their function is not limited
      to the guidance of growing axons during embryogenesis. Axon guidance cues fulfill
      additional roles in angiogenesis, cell migration and the immune system, and often
      display sustained expression in adulthood. Here we focus on the semaphorin (Sema)
      family and review their proposed functions in the adult nervous system. Several
      semaphorin family members continue to be expressed in the adult brain and spinal
      cord, and increasing evidence indicates that their expression is regulated upon
      nervous system injury in rodents and in neuropathology in humans. The available
      evidence suggests that semaphorins might significantly contribute to the
      maintenance and stability of neuronal networks. Furthermore, semaphorins could
      play important roles in the regeneration, or failure thereof, of neuronal
      connections. In the future, genetic manipulation of semaphorins and their
      receptors in the adult intact and injured nervous system should provide a deeper
      insight into the mechanisms by which semaphorin signaling contributes to
      structural plasticity and regeneration in the adult brain.

PMID- 14687985
TI  - Functional analysis of the mutated Epstein-Barr virus oncoprotein LMP1(69del):
      implications for a new role of naturally occurring LMP1 variants.
AB  - BACKGROUND AND OBJECTIVES: The role of carboxyterminal deletions of the latent
      membrane protein-1 (LMP1) in Epstein-Barr virus (EBV) infection and oncogenesis
      is unclear. Here we describe functional properties of a rare 69-bp LMP1 deletion
      mutant (LMP1(69del)) isolated from a patient with polyclonal B-cell
      lymphocytosis. DESIGN AND METHODS: Colony focus assay was used to evaluate the
      transforming capacity of LMP1(69del) in comparison to that of wild-type LMP1 from
      EBV strain B95/8. Transient transfectants of B-, T-, epithelial and 3T3 cells,
      and stable transfectants with ecdysone-inducible LMP1 expression were produced.
      The signaling capacity of both LMP1s on nuclear transcription factors NFkappaB
      and AP-1 were studied. Secretion of matrix metalloproteinase MMP-9, apoptosis,
      and EBV lytic and latent gene expression were also investigated. RESULTS:
      LMP(69del) showed transforming properties comparable to those of the wild-type
      oncoprotein. Induction of NFkappaB but a markedly reduced influence on AP-1 were
      observed. Both oncoproteins induced secretion of MMP-9, and enhanced pre
      apoptotic effects in Jurkat-T cells leading to increased Fas/Apo-1 and
      doxorubicin-mediated apoptosis. Furthermore, LMP1(69del) showed a more effective
      down-regulation of the EBV lytic cycle master gene BZLF1(Zebra) than did wild
      type LMP1. INTERPRETATION AND CONCLUSIONS: (i) LMP1(69del) possesses oncogenic
      properties, (ii) the observed impaired activity on AP-1 does not interfere with
      MMP-9 induction, (iii) the enhanced inhibition of BZLF1 could compensate for
      previously described mutations of our isolate leading to a more lytic phenotype
      and may be responsible for counteracting permanent virus replication in the
      chronic active EBV syndrome observed in this patient.

PMID- 14687986
TI  - Lhx2 expression in hematopoietic progenitor/stem cells in vivo causes a chronic
      myeloproliferative disorder and altered globin expression.
AB  - BACKGROUND AND OBJECTIVES: Chronic myeloproliferative disorders (CMDs) are
      thought to be due to mutation(s) in a single clone at the level of the
      hematopoietic stem cell (HSC). Such mutations and additional mutations causing
      progression of the disease are largely unknown. Chronic myeloid leukemia (CML) is
      a CMD characterized by a chromosomal translocation between chromosomes 9 and 22
      creating the fusion protein BCR-ABL. This translocation has also been suggested
      to cause mis-expression of the LIM-homeobox gene Lhx2 in hematopoietic cells. We
      have previously shown that Lhx2 expression in mouse HSC generates cytokine
      dependent stem cell-like cell lines that can produce long-term repopulation in
      stem cell-deficient mice. DESIGN AND METHODS: Since the consequences of Lhx2
      expression in hematopoietic cells in vivo were unknown, mice engrafted with the
      stem cell-like cell lines were analyzed in detail for any pathologic changes.
      RESULTS: Expression of Lhx2 was maintained in vivo and most engrafted mice
      developed a myeloproliferative disorder characterized by splenomegaly,
      extramedullary hematopoiesis and anemia. The disorder was transplantable and the
      Lhx2-expressing cells could also cause acute leukemia. The anemia was due to both
      a reduced number of circulating erythrocytes and a reduced mean corpuscular
      hemoglobin concentration (MCHC). INTERPRETATION AND CONCLUSIONS: These
      observations suggest that constitutive expression of Lhx2 in hematopoietic cells
      causes CMD, and also that a novel cell-autonomous mechanism can contribute to
      anemia.

PMID- 14687987
TI  - Fludarabine + prednisone +/- alpha-interferon followed or not by alpha-interferon
      maintenance therapy for previously untreated patients with chronic lymphocytic
      leukemia: long term results of a randomized study.
AB  - BACKGROUND AND OBJECTIVES: Fludarabine is an effective therapy for patients with
      chronic lymphocytic leukemia (CLL) and interferon-alpha (IFN-alpha) has been
      reported to have anti-leukemic activity in CLL patients. A randomized study was
      designed to evaluate whether the addition of IFN-alpha to a first-line treatment
      with fludarabine and prednisone could increase the response rate in patients with
      advanced CLL and whether IFN-alpha given as maintenance therapy could improve the
      duration of response. DESIGN AND METHODS: One hundred and thirty-three patients
      were randomized to receive fludarabine (25 mg/m2/i.v., days 9-13) and prednisone
      (20 mg/m2, days 1, 3, 5, 7 and 14 and 40 mg/m2, days 9-13) (arm A: 66 patients)
      or in addition to the same schedule, IFN-alpha (2 MUI/sc, days 1, 3, 5, 7, 9, 11,
      13 and 15) (arm B: 67 patients). Seventy-eight patients responsive to therapy
      entered the post-remission phase of the study in which 41 patients were
      randomized to receive IFN-alpha (3 MUI three times a week) and 37 to clinical
      observation. RESULTS: A similar response rate (complete responses + partial
      responses) was observed in the 2 arms: 86% for arm A and 84% for arm B (p = 0.4).
      A longer response duration was observed in patients who achieved a complete
      response (p = 0.001) and in patients who received maintenance therapy with IFN
      alpha (p < 0.05). However, the quality of response was the only significant and
      independent factor influencing response duration (p < 0.01). No benefits in terms
      of infection-related mortality and morbidity could be ascribed to IFN-alpha
      administration. INTERPRETATION AND CONCLUSIONS: In previously untreated CLL
      patients with advanced disease a high response rate is obtained from first-line
      fludarabine and prednisone and no benefit is derived from the addition of IFN
      alpha to this regimen. The achievement of a good quality response to therapy was
      the only independent predictor of a prolonged response.

PMID- 14687988
TI  - Morphologic, flow cytometric and cytogenetic evaluation of bone marrow
      involvement in B-cell lymphoma.
AB  - BACKGROUND AND OBJECTIVES: Flow cytometric immunophenotypic analysis (FC) and
      cytogenetic analysis are essential techniques for the diagnosis and
      classification of many hematologic disorders. The roles of these analyses in B
      cell lymphoma to detect bone marrow (BM) involvement in clinical staging and to
      evaluate the effectiveness of treatments have not yet been determined. The aim of
      this study was to evaluate the usefulness of FC and cytogenetic analysis in the
      assessment of BM involvement in B-cell lymphoma. DESIGN AND METHODS: We
      retrospectively analyzed the usefulness of three-color FC and cytogenetic
      analysis in detecting BM involvement by examining 104 BM specimens from patients
      with B-cell lymphoma. RESULTS: By morphologic evaluation of BM biopsy (BMB), the
      BM was involved in 11 specimens (10.6%), not involved in 92 specimens (88.5%) and
      involvement could not be determined in 1 specimen (0.9%). FC identified a
      monoclonal B-cell population in 24 samples (23.1%). FC detected BM involvement in
      all but one BMB positive sample, and showed negative results in a BMB
      undetermined sample. Conclusively, FC found a monoclonal B-cell population in 14
      of 92 BMB negative samples (15.2%). In particular, FC detected smaller amounts of
      BM involvement than did morphologic evaluation. Cytogenetic analysis revealed
      clonal abnormalities in only 9 of 104 samples (8.7%). However, 2 of these 9
      samples were from patients with aggressive lymphoma with complex structural
      chromosomal abnormalities detectable only by cytogenetic analysis. INTERPRETATION
      AND CONCLUSIONS: Although morphologic evaluation of adequate amounts of BMB
      specimens remains essential for the evaluation of BM involvement, three-color FC
      is more sensitive in detecting BM disease than morphologic or cytogenetic
      analysis. Cytogenetic analysis seems to have low sensitivity and specificity, but
      this method may improve the detection of BM involvement in a small number of
      aggressive lymphomas that have many mitotic cells.

PMID- 14687990
TI  - High dose chemotherapy and autologous stem cell transplantation in patients with
      peripheral T-cell lymphoma not achieving complete response after induction
      chemotherapy. The GEL-TAMO experience.
AB  - BACKGROUND AND OBJECTIVES: Patients with aggressive non-Hodgkin's lymphomas (NHL)
      who do not obtain a complete response (CR) after induction chemotherapy have a
      poor prognosis. However, provided they are sensitive to the first regimen of
      chemotherapy, 25-40% of them with a B-cell phenotype may achieve long-term
      survival when treated with high dose chemotherapy and autologous stem cell
      transplantation (HDC/ASCT). The aim of this study was to analyze the efficacy of
      this therapy in the corresponding patients with peripheral T-cell lymphoma
      (PTCL). DESIGN AND METHODS: We retrospectively evaluated the efficacy of ASCT in
      35 patients with PTCL from the GEL-TAMO registry, who did not achieve a CR to
      standard induction chemotherapy regimens for aggressive NHL. Thirty-one patients
      underwent transplantation after achieving a partial response (PR) and 4 patients
      were non-responders. RESULTS: Following HDC/ASCT, 23 (66%) of the patients
      achieved a CR, 4 (11%) a PR and in 7 (20%) cases the transplant failed. One
      patient was not evaluated because of early toxic death. With a median follow-up
      of the survivors of 37.5 months, 18 patients (51%) are alive and 15 patients
      (43%) are free of disease. Transplant-related mortality rate at 100 days was 11%
      and at 5 years the probabilities of survival, freedom from progression and
      disease-free survival for complete responders were 37%, 36% and 55% respectively.
      Pre-transplant lactate-dehydrogenase level, age-adjusted International Prognostic
      Index (aa-IPI) and tumor score correlated with survival. INTERPRETATION AND
      CONCLUSIONS: One third of the patients with PTCL who fail to achieve CR to the
      first chemotherapeutic regimen can be rescued with HDC/ASCT. Pre-transplant
      values of IPI and tumor score risk systems for aggressive lymphomas were useful
      to predict subsequent survival.

PMID- 14687989
TI  - A pilot study of CODOX-M/IVAC in primary refractory or relapsed high-grade non
      Hodgkin's lymphoma. A Scotland and Newcastle Lymphoma Group Study.
AB  - BACKGROUND AND OBJECTIVES: The prognosis in patients with primary refractory or
      relapsed high grade non-Hodgkin's lymphoma (NHL) is very poor--the 5-year
      survival being generally reported at 10%. DESIGN AND METHODS: Multiple salvage
      regimens have been investigated and, while response rates of 50-80% have been
      noted in selected patients, the long-term prognosis remains poor. Following the
      encouraging results in high risk Burkitt's and Burkitt-like lymphoma using the
      CODOX-M and IVAC protocols, we performed a pilot study using a similar regimen in
      patients with primary refractory or relapsed high grade NHL. RESULTS: The
      regimens were modified by a reduction in the intensity of intrathecal therapy. It
      was planned to mobilize peripheral blood stem cells following the IVAC cycle for
      use in subsequent autologous peripheral blood stem cell transplantation in
      chemosensitive patients. The initial plan was to recruit 50 patients, but the
      study was closed after 8 due to excessive toxicity. INTERPRETATION AND
      CONCLUSIONS: We conclude that the CODOX-M/IVAC regimen is too toxic for this
      group of patients and does not result in better response rates than those to
      currently available salvage regimens.

PMID- 14687991
TI  - Glanzmann's thrombasthenia: modulation of clinical phenotype by alpha2C807T gene
      polymorphism.
AB  - BACKGROUND AND OBJECTIVES: The expression of Glanzmann's thromboasthenia (GT)
      varies, even among patients carrying the same mutation. It is conceivable that
      other gene loci may influence the clinical expression of GT and lead to specific
      phenotypes. DESIGN AND METHODS: To investigate GT clinical heterogeneity we
      screened 25 GT patients with a known alpha(IIb)beta3 molecular defect for
      thrombophilic mutations (FV Leiden, FII A20210) and the platelet glycoprotein
      (GP) alpha2 C807T gene polymorphism. RESULTS: The FV Leiden mutation was found in
      1 patient, the FII A20210 mutation in none. Three GT patients were homozygous for
      the T807 allele and showed a mild clinical expression of GT whereas none of the
      patients presenting with a moderate or severe GT phenotype carried the alpha2 TT
      genotype (p=0.037, two-sided exact test). In patients carrying the same mutation,
      the clinical GT phenotype was milder in those with the TT807 genotype.
      INTERPRETATION AND CONCLUSIONS: Since the platelet alpha2 C807T gene polymorphism
      is associated with alpha2beta1 receptor density on the platelet surface, our
      findings suggest that the level of alpha2beta1 on platelets may be an additional
      factor affecting GT clinical expression.

PMID- 14687992
TI  - An antifibrinolytic effect associated with an anti-factor V antibody in a patient
      with severe thrombophilia.
AB  - BACKGROUND AND OBJECTIVES: The case of a patient with thrombotic manifestations
      and severe activated protein C resistance due to an anti-factor V antibody has
      recently been described. Since activated protein C (APC) is also profibrinolytic
      we wanted to determine whether the presence of antibodies interfering with the
      anticoagulant activity of APC also inhibits its profibrinolytic effect. DESIGN
      AND METHODS: Plasma clots were formed in the presence of tissue plasminogen
      activator, thrombin, phospholipids, Ca++, and various concentrations of APC, and
      the rate of lysis was monitored over time by the reduction in turbidity.
      Generation of endogenous thrombin and activation of thrombin activatable
      fibrinolysis inhibitor (TAFI) were also determined during fibrinolysis by
      clotting and spectrophotometric assays, respectively. RESULTS: Addition of APC to
      the patient's plasma failed to stimulate fibrinolysis even at a concentration 4
      times higher than that needed to produce the maximal effect in control plasma.
      Removal of IgG from the patient's plasma fully restored the fibrinolytic response
      to APC. Accordingly, addition of the patient's IgG to control plasma caused a
      concentration-dependent inhibition of APC-dependent fibrinolysis. The patient's
      IgG did not, however, inhibit the profibrinolytic effect of heparin.
      Determination of thrombin and activated TAFI generation during clot lysis showed
      that APC inhibited the generation of these enzymes by less than 20% in plasma
      supplemented with the patient's IgG as opposed to >80% in a control sample.
      INTERPRETATION AND CONCLUSIONS: Our data suggest that the anti-factor V antibody
      inhibits fibrinolysis by antagonizing the anticoagulant effect of APC thereby
      favoring thrombin generation and TAFI activation. Impaired fibrinolysis may
      represent an additional mechanism contributing to thrombosis in patients with
      severe APC resistance phenotype.

PMID- 14687993
TI  - Uncontrolled-rate freezing of peripheral blood progenitor cells allows successful
      engraftment by sparing primitive and committed hematopoietic progenitors.
AB  - BACKGROUND AND OBJECTIVES: Uncontrolled-rate freezing (URF) techniques, which are
      fast and easy, could represent an attractive alternative to controlled-rate
      cryopreservation procedures which are time consuming and require high-level
      technical abilities. It was the aim of the present study to evaluate, on a
      routine basis, whether URF might spare primitive hematopoietic progenitors and
      maintain engrafting capacity. DESIGN AND METHODS: One-hundred and nineteen
      peripheral blood progenitor cells (PBPC) collections from 104 patients with
      hematologic malignancies were cryopreserved in bags, with an URF procedure, in a
      cryoprotectant solution consisting of PBS, HSA and 10% DMSO and stored in liquid
      nitrogen. PBPC bags were tested before cryopreservation and at thawing for
      primitive (LTC-IC) and committed hematopoietic progenitors (CFU-Mix, BFU-E, CFU
      GM) by means of long- and short-term culture assays, respectively. In addition,
      PBPC bags were evaluated for CD34+ cell numbers. RESULTS: Although thawing was
      associated with a statistically significant reduction of the absolute number of
      nucleated cells, recovery of LTC-IC, CFU-Mix, BFU-E, CFU-GM and CD34+ cells was
      not affected by the freezing/thawing procedures. No adverse effects were reported
      at thawing and only mild transient reactions were recorded in 22 patients during
      reinfusion of cryopreserved PBPC. All the patients underwent myeloablative
      therapy followed by reinfusion of PBPC, and prompt and rapid hematopoietic
      recovery was obtained in all patients. INTERPRETATION AND CONCLUSIONS: Our
      freezing procedure is fast and easy, and allows rapid hematopoietic recovery
      after myeloablative therapy by sparing primitive and committed hematopoietic
      progenitors. Our study strongly supports technical improvements aimed at cost
      reduction and feasibility of routine freezing procedures.

PMID- 14687994
TI  - Dendritic cell viability is decreased after phagocytosis of apoptotic tumor cells
      induced by staurosporine or vaccinia virus infection.
AB  - BACKGROUND AND OBJECTIVES: Dendritic cells (DC) primed with tumor antigens can
      effectively mediate the regression of a variety of established solid malignancies
      in both murine and human models. Several experimental studies indicate that
      apoptotic bodies are an optimal source of tumor antigens for ex vivo priming of
      DC. However, the clinical use of killed tumor cells as a source of antigens will
      require an optimal methodology to induce effective tumor cell apoptosis. DESIGN
      AND METHODS: The goal of this study was to compare the efficiency of three agents
      for inducing neoplastic B lymphocyte apoptosis; staurosporine, infection by
      modified vaccinia (MVA) viral particles and ultraviolet C (UVC) radiation.
      RESULTS: The three methods were finely tuned to induce apoptosis in more than 90%
      of tumor cells after 24 hours of exposure. However, the viability of monocyte
      derived DC, loaded with B-cell tumor apoptotic bodies induced by staurosporine or
      MVA viral particles, decreased dramatically within 48 hours after phagocytosis of
      the killed neoplastic cells. The persistence of the apoptosis-inducing agents in
      the apoptotic bodies and not in the tumor supernatant, was responsible for the
      observed damage to DC viability. In contrast, DC viability was not affected after
      uptake of tumor cells killed through UVC-irradiation. Furthermore, B
      lymphoblastic cell line (LCL)-specific T cells were reactivated by DC loaded with
      apoptotic bodies induced by UVC-rays. INTERPRETATION AND CONCLUSIONS: Since the
      method used to induce tumor cell apoptosis might be detrimental to DC viability,
      these findings should be considered when designing anticancer vaccination
      programs.

PMID- 14687995
TI  - Utility of percutaneous lung biopsy for diagnosing filamentous fungal infections
      in hematologic malignancies.
AB  - BACKGROUND AND OBJECTIVES: The incidence of invasive filamentous fungal
      infections in hematologic patients is increasing as a consequence of high dose
      chemotherapy and bone marrow transplant procedures. Mortality is usually very
      high. The diagnosis is often difficult and yet a fast, accurate diagnosis is of
      fundamental importance for treating the infection and planning subsequent
      management of the hematologic disease. We evaluated the sensitivity of computed
      tomography (CT)-guided percutaneous biopsy in diagnosing pulmonary fungal
      infections. DESIGN AND METHODS: Between 1997 and 2002 we performed 17 CT-guided
      percutaneous transthoracic lung biopsies in 17 hematologic patients with
      suspected filamentous fungi infection with negative BAL, to obtain a certain
      diagnosis and to know what species of fungi was responsible for infection. In all
      cases suspected mycosis began during the post-chemotherapy aplastic period.
      Patients were receiving antifungal therapy at the time of all biopsies. When the
      platelet count rose above 50 x 10(9)/L, CT-guided percutaneous lung biopsy with
      fine-needle aspiration for cytology was performed. RESULTS: Twelve of 17 patients
      had histologic confirmation of the fungal infection (70.5%), 8 with Aspergillus
      spp. 4 with Mucorales spp. Biopsies provided non-specific results in 4 cases; in
      2 of these cases, clinical course and response to therapy confirmed the diagnosis
      of mycosis; in the last case bronchoalveolar carcinoma was found as a new
      diagnosis. Cultures were positive in only 6 cases, all for Aspergillus spp. The
      sensitivity of CT-guided percutaneous lung biopsy was 70.6% and its positive
      predictive value (PPV) was 100%. This procedure provided an immediate diagnosis
      and only one side-effect (1 pneumothorax, without complications). INTERPRETATION
      AND CONCLUSIONS: Histologic discrimination between aspergillosis and mucormycosis
      is very important for deciding secondary prophylaxis during transplant
      procedures, because Mucor is usually resistant to azoles.

PMID- 14687996
TI  - Quantification of risk factors for venous thromboembolism: a preliminary study
      for the development of a risk assessment tool.
AB  - BACKGROUND AND OBJECTIVES: Venous thromboembolism is a frequent and serious
      disorder influenced by numerous factors. As the first step in creating a tool to
      assess an individual patient's risk of venous thromboembolism, we carried out a
      literature review in order to quantify risk factors for venous thromboembolism.
      EVIDENCE AND INFORMATION SOURCES: Risk factors were identified as being either
      predisposing, that is, those risks presented by a patient prior to hospital
      admission, or exposing, that is, those risks occurring when a patient is
      hospitalized for a certain medical condition or surgical procedure. Predisposing
      risk factors were classified with regard to the patients' characteristics
      (including general characteristics and inherent risk factors), and recent and
      chronic clinical conditions. RESULTS: The major predisposing factors among the
      patients' characteristics were age, hormonal therapy and personal history of
      venous thromboembolism, along with inherited coagulation factor abnormalities.
      Clinical situations associated with the highest risk of venous thromboembolism
      were recent surgery, hospitalization for medical conditions and immobilization,
      moderate to severe congestive heart failure, and malignancy. CONCLUSIONS: This
      literature review will assist in the development of a suitable risk assessment
      tool for aiding healthcare professionals to decide whether to employ
      thromboprophylaxis, and, if so, to select the appropriate type and duration of
      prophylaxis.

PMID- 14687997
TI  - Reticulocyte indices rapidly reflect an increase in iron availability for
      erythropoiesis.

PMID- 14687998
TI  - Combined therapy with desferrioxamine and deferiprone in thalassemic patients:
      effect on urinary iron excretion.

PMID- 14687999
TI  - Lack of Bcr-Abl point mutations in chronic myeloid leukemia patients in chronic
      phase before imatinib treatment is not predictive of response.

PMID- 14688000
TI  - Deletion of sequences telomeric of the EVI1 gene in 3q26 associated with a novel
      pericentric inv(3)(p25q26) in a patient with acute myelogenous leukemia.

PMID- 14688001
TI  - Bone marrow and peripheral blood hematopoietic reserve in patients with B-cell
      chronic lymphocytic leukemia.

PMID- 14688002
TI  - The importance of follow-up biopsies of clinically suspicious lymphadenopathy in
      nodular lymphocyte predominant Hodgkin's lymphoma.

PMID- 14688003
TI  - Thalidomide plus oral melphalan for advanced multiple myeloma: a phase II study.

PMID- 14688004
TI  - The Gly331Ser mutation in factor VII in Europe and the Middle East.

PMID- 14688005
TI  - Genetic determinants of iron metabolism plasma phenotypes and their relationship
      with risk of thrombosis.

PMID- 14688006
TI  - Feasibility of idiotype vaccination in relapsed B-cell malignancies.

PMID- 14688007
TI  - Cardiac lymphoma successfully treated with high dose chemotherapy followed by
      autologous haematopoietic stem cell transplantation.

PMID- 14688008
TI  - Spontaneous mutation of the hemoglobin Leiden (beta 6 or 7 Glu-->0) in a Thai
      girl.
AB  - We report a case of 12-year old Thai girl suffering from mild non-transfusion
      dependent thalassemia intermedia. She is the single child in her family. On
      examination she looked pale; there was no hepatosplenomegaly. The Hb
      concentration was 9 g/dL. Hb typing and molecular mutation study revealed
      compound heterozygosity for HbE and Hb Leiden (alpha2beta26/7-Glu, codon 6/7
      GAG). The proportion of HbE was 47% whereas that of Hb Leiden was 39%. The
      patient had no HbA. Hb typing of her father and mother revealed HbE trait, and no
      Hb Leiden was demonstrated. As the paternity test confirmed the parenthood, we
      assume that Hb Leiden has arisen by spontaneous mutation. A study of the beta<
      or= -globin gene framework by molecular cloning and subsequent DNA sequencing of
      the beta-globin gene in the members of the family indicated that the Hb Leiden
      mutation occurred on a maternal inherited chromosome. The deletion of codon 6 or
      7 (-GAG) of the beta-globin gene in the patient may be due to an unequal crossing
      over during the mother's oogenesis.

PMID- 14688009
TI  - Huge post-operative ulcer following hydroxyurea therapy in a patient with
      polycythemia vera.
AB  - A 75-year old woman was referred to our hospital due to a worsening post
      operative cutaneous ulcer. She had a history of polycythemia vera and had been
      treated with a daily dose of 500mg hydroxyurea (HU) for six years. She underwent
      a right hernioplasty in another hospital in September 2002. Two days after the
      hernioplasty, the skin around the wound became erythematous and necrosis was
      observed. Even with the administration of antibiotics and debridment was
      performed three times, her condition deteriorated and she was referred to our
      hospital. On admission, a 22x15cm ulcer was observed on the lower abdomen. With
      termination of HU, the cutaneous ulcer became smaller and with the withdrawal of
      other medication, the ulcer size continued to decrease. Although post-operative
      cutaneous ulcer complicated by HU administration has rarely been reported, our
      case clearly indicates that early termination of HU should be considered when
      patients develop symptoms preceding cutaneous ulcer.

PMID- 14688011
TI  - inv(3)(q21q26) in AML/MDS: Monitoring of the malignant clone with interphase
      FISH.

PMID- 14688010
TI  - Low dose gemtuzumab ozogamicin for relapsed acute myeloid leukaemia in elderly.

PMID- 14688012
TI  - PAS positive monocytes in Whipple s disease.

PMID- 14688013
TI  - International Normalized Ratio (INR) increase in patients taking oral
      anticoagulant therapy (OAT) and using sildenafil (Viagra).

PMID- 14688014
TI  - Clinical relevance of inherited thrombophilia in implantation failure: who needs
      to be screened?

PMID- 14688015
TI  - Screening of thrombophilia in women with failure of embryo implantation: far from
      being recommended.

PMID- 14688016
TI  - Polymorphisms in DNA repair and metabolic genes in bladder cancer.
AB  - We investigated the association of urinary bladder cancer with genetic
      polymorphisms in the xeroderma pigmentosum complementation group C (XPC), group D
      (XPD) and group G (XPG), X-ray repair cross-complementing group 1 (XRCC1) and
      group 3 (XRCC3), Nijmegen breakage syndrome 1 (NBS1), cyclin D1, methylene
      tetrahydrofolate reductase (MTHFR), NAD(P)H dehydrogenase quinone 1 (NQO1), H-ras
      and glutathione S-transferase theta 1 (GSTT1) genes. Bladder cancer patients from
      the different hospitals in Stockholm County Council area and matching controls
      were genotyped for different polymorphisms. The frequency of the variant allele
      for A/C polymorphism in exon 15 of the XPC gene was significantly higher in the
      bladder cancer cases than in the controls (OR 1.49, 95% CI 1.16-1.92, P = 0.001).
      The variant allele homozygote genotype for the T/C polymorphism in exon 1 of the
      H-ras gene was associated with a decreased risk for bladder cancer (OR 0.12, 95%
      CI 0.02-0.67, P = 0.006). The variant allele genotypes for the single nucleotide
      polymorphisms (SNPs) in DNA repair genes, XPG and NBS1, showed a marginal
      association with the occurrence of bladder cancer (OR 0.38, 95% CI 0.15-0.94, P =
      0.03 and OR 1.64, 95% CI 0.92-2.90, P = 0.09, respectively). We also report a
      positive correlation between the null homozygote of GSTT1 with the risk of
      bladder cancer (OR 2.54, 95% CI 1.32-4.98, P = 0.003). For other polymorphisms
      included in this study, NBS1 Glu185Gln, XPD Lys751Gln, XPG Asp1104His, XRCC1
      Arg399Gln, XRCC3 Thr241Met, cyclin D1 Pro242Pro, MTHFR Ala222Val and Glu429Ala,
      NQO1 Arg139Trp and Pro187Ser, no significant differences for genotype
      distributions and allele frequencies between the bladder cancer cases and the
      controls were observed in the present study.

PMID- 14688017
TI  - Ras gene mutations in patients with acute myeloid leukaemia and exposure to
      chemical agents.
AB  - Mutations of the N- and K-ras genes occur in approximately 15-30% of acute
      myeloid leukaemia patients. The role of the oncogenic ras in leukaemogenesis
      remains unclear. Few studies have revealed that mutations in the ras oncogene
      family are more probably found in acute myeloid leukaemia patients with previous
      exposure to toxic agents. A case-case study was conducted in the areas of
      Florence and Turin, Italy, to investigate whether the presence of N- and K-ras
      mutations in acute myeloid leukaemia patients was related to a higher frequency
      of exposure to chemicals. During a 3-year period, 111 acute myeloid leukaemia
      patients were enrolled. All the patients were interviewed using a semi-structured
      questionnaire collecting data on residential history, occupation, personal habits
      and pathological history. The presence of N- and K-ras mutations was analysed by
      amplification and synthetic oligonucleotide probes and by the so-called
      polymerase chain reaction amplification for specific alleles technique. A total
      of 34 (30.6%) patients were found to harbour ras mutations in N-ras and/or K-ras.
      Fourteen patients (12.6%) had a single ras mutation and 20 patients (18%) had two
      ras mutations. A positive association between a priori at risk jobs and ras
      mutations was found, based on nine exposed cases; the odds ratio, adjusted by
      age, sex and previous X-ray and/or chemotherapy was 2.8 (95% confidence
      intervals: 0.9-9.0). When considering only subjects with two ras mutations the
      odds ratio was 4.8 (95% confidence intervals: 1.2-18.8). The odds ratio for a
      previous X-ray and/or chemotherapy was 16.2 (95% confidence intervals: 1.8
      755.9); when only subjects with two ras mutations were considered, the odds ratio
      was 26.1 (95% confidence intervals: 2.5-1248.9). In conclusion, our data suggest
      that ras oncogene mutations might identify a group of leukaemia in people with
      previous X-ray/chemotherapy or with exposure to chemical agents in the work
      environment.

PMID- 14688018
TI  - Cytotoxic and genotoxic effects of beta-carotene breakdown products on primary
      rat hepatocytes.
AB  - According to Siems and colleagues, 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. This finding may be 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 of the genotoxic action of suspect mutagens/carcinogens
      we therefore investigated a beta-carotene cleavage products mixture (CP), apo8'-
      carotenal (apo8') and beta-carotene utilizing primary cultures of rat
      hepatocytes. The end-points tested were: the mitotic index, the percentage of
      necrotic and apoptotic cells, micronucleated cells, chromosomal aberrations and
      sister chromatid exchanges (SCE). Our results indicate a genotoxic potential of
      both CP and apo8' already at the concentrations 100 nM and 1 microM, i.e. at
      pathophysiologically relevant levels of beta-carotene and beta-carotene breakdown
      products. A 3 h treatment with CP induced statistically significant levels of
      micronuclei at concentrations of 0.1, 1 and 10 microM and chromosomal aberrations
      at concentrations of 1, 5 and 10 microM. Apo8' induced statistically significant
      levels of micronuclei at concentrations of 0.1, 1 and 5 microM and chromosomal
      aberrations at concentrations of 0.1, 1 and 10 microM. Statistically significant
      increases in SCE induction were only observed at a concentration of 10 microM CP
      and apo8'. In contrast, no significant cytotoxic effects of these substances were
      observed. Since beta-carotene induced neither significant cytotoxic nor genotoxic
      effects at concentrations ranging from 0.01 up to 10 microM, these observations
      indicate that most likely 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 Trial (CARET).

PMID- 14688019
TI  - Identification of tumour-specific epigenetic events in medulloblastoma
      development by hypermethylation profiling.
AB  - Medulloblastoma arises in the cerebellum and is the most common malignant brain
      tumour of childhood, however its molecular basis is not well understood. To
      assess the role of aberrant epigenetic events in medulloblastoma and identify
      critical genes in its development, we profiled the promoter methylation status of
      11 candidate tumour-suppressor genes (TSGs; p14(ARF), p15(INK4b), p16(INK4a),
      CASP8, HIC1, EDNRB, TIMP3, TP73, TSLC1, RIZ1 and RASSF1A) in medulloblastoma cell
      lines, primary tumours and the normal cerebellum. Gene-specific TSG methylation
      was a significant feature of both medulloblastomas and the cerebellum. Extensive
      hypermethylation of RASSF1A was detected frequently in medulloblastomas but not
      in the normal cerebellum (41/44 primary tumours versus 0/5 normal cerebella). In
      contrast, complete methylation of HIC1 and CASP8 in a subset of primary tumours
      (17/44 and 14/39) occurred against a consistent background of partial methylation
      in the normal cerebellum. These data therefore indicate that extensive
      methylation of RASSF1A, HIC1 and CASP8 are tumour-specific events in
      medulloblastoma. Moreover, methylation of these genes in medulloblastoma cell
      lines was associated with their epigenetic transcriptional silencing and
      methylation-dependent re-expression following treatment with the DNA
      methyltransferase inhibitor, 5-aza-2'-deoxycytidine. The remaining genes studied
      showed either low frequency methylation (p14(ARF), p16(INK4a), RIZ1; <7% of
      cases), no evidence of methylation (p15(INK4b), TIMP3, TP73, TSLC1), or
      comparable patterns of methylation in the normal cerebellum (EDNRB), suggesting
      that their hypermethylation does not play a major role in medulloblastoma. Our
      data demonstrate that tumour-specific hypermethylation affects only a subset of
      genes, and does not support the existence of a concordant methylation phenotype
      in this disease. We conclude that epigenetic TSG inactivation is a significant
      feature of medulloblastoma, and identify RASSF1A, HIC1 and CASP8 as potentially
      critical genes in its pathogenesis. Furthermore, methylation observed in the
      normal cerebellum emphasises the requirement for appropriate control tissues when
      assessing the tumour-specificity of TSG hypermethylation.

PMID- 14688020
TI  - Diet, GSTM1 and GSTT1 and head and neck cancer.
AB  - A decreased incidence of squamous cell carcinoma of the head and neck (SCCHN)
      associated with fruit and vegetable intake may act through chemopreventive
      compounds, which may be more available to persons homozygous for the deletion
      genotypes of the glutathione S-transferase (GST). We evaluated interactions
      between fruits and vegetables and GSTM1 and GSTT1 on incidence of SCCHN using
      data from a case-control study of 149 cases and 180 age- and gender-matched
      controls. After adjustment for age, gender, race, tobacco and alcohol use, weekly
      consumption of four or more servings of raw vegetables was inversely associated
      with SCCHN [odds ratio (OR) = 0.66, 95% confidence intervals (CI) 0.30-1.3].
      Contrary to expectation, relatively high intake of cooked vegetables (14 or more
      weekly servings) and legumes (two or more weekly servings) were associated with
      increased incidence (OR = 2.5, 95% CI 1.1-6.0; OR = 2.5, 95% CI 1.2-5.2,
      respectively). In general, our results did not suggest a clear or consistent
      pattern of modification by GST genotypes of the association between foods and
      SCCHN. For example, eating cruciferous vegetables, foods of a priori interest,
      and having the GSTM1-deletion genotype was not associated with the expected
      reduction in incidence compared with abstaining from cruciferous vegetable intake
      and having the GSTM1-present genotype. Among non-consumers of cruciferous
      vegetables, the GSTM1-deletion genotype was inversely associated with SCCHN (OR =
      0.55, 95% CI 0.07-4.2). Raw vegetables were associated with a reduction in
      incidence only among persons with the GSTM1-deletion genotype (OR = 0.69, 95% CI
      0.29-1.6), whereas either factor alone had a null association. Future research of
      GST-diet interactions and SCCHN would benefit from larger, population-based
      studies.

PMID- 14688021
TI  - A functional polymorphism in the SULT1A1 gene (G638A) is associated with risk of
      lung cancer in relation to tobacco smoking.
AB  - Sulfotransferase 1A1, an important member of sulfotransferase superfamily, is
      involved in the biotransformation of many compounds including tobacco
      carcinogens. A single nucleotide polymorphism (G638A) in the sulfotransferase 1A1
      (SULT1A1) gene causes Arg213His amino acid change and consequently results in
      significantly reduced enzyme activity and thermostability. We thus hypothesized
      that the variant SULT1A1 allele may protect against the risk of lung cancer
      related to tobacco smoking. To examine this hypothesis, we analyzed 805 patients
      with lung cancer and 809 controls for this polymorphism in a hospital-based, case
      control study. We observed that, compared with the GG genotype, the variant
      SULT1A1 genotype (638GA or AA) was associated with a significantly increased risk
      for overall lung cancer [odds ratio (OR) 1.85; 95% confidence interval (CI) 1.44
      2.37]. Stratification analysis showed that the increased risk of lung cancer
      related to the variant SULT1A1 genotypes was more pronounced in younger subjects
      and limited to smokers but not non-smokers [OR 2.28 (95% CI 1.66-3.13) versus OR
      1.35 (95% CI 0.91-1.99); P for homogeneity = 0.000]. Furthermore, the risk of
      lung cancer for the variant genotypes was increased consistently with cumulative
      smoking dose, with the ORs being 1.66 (95% CI, 0.75-3.68), 2.28 (95% CI, 1.47
      3.54) and 3.35 (95% CI, 1.71-6.57) for those who smoked <15 pack-years, 15-36
      pack-years and >36 pack-years, respectively (P for trend = 0.000). When analysis
      was stratified by histological subtypes of lung cancer, consistent results were
      observed for all three major types of the cancer, i.e. squamous cell carcinoma,
      adenocarcinoma and other types. Our results, which are against the original
      hypothesis, demonstrate that the variant SULT1A1 638A allele is associated with
      susceptibility to lung cancer in relation to tobacco smoking.

PMID- 14688023
TI  - Benzyl isothiocyanate inhibits excessive superoxide generation in inflammatory
      leukocytes: implication for prevention against inflammation-related
      carcinogenesis.
AB  - Inhibitors of excessive superoxide (O2-) generation have been indicated to be
      more effective antioxidants than radical scavengers because O2- anion is one of
      the precursors of several types of reactive oxygen species (ROS). We demonstrated
      here that benzyl isothiocyanate (BITC) is a potent inhibitor of leukocytic NADPH
      oxidase generating a great amount of O2- in oxidative burst. The exposure of BITC
      to the differentiated HL-60 cells resulted in the inhibition of 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced O2- generation, while the
      methylthiocarbamate analog of BITC, hardly reactive with thiols including
      glutathione and protein sulfhydryl, did not show any effect. Pre-treatment of the
      cells with diethyl maleate significantly potentiated the BITC-induced inhibition,
      while pre-treatment with N-acetyl-cysteine counteracted it. These results led us
      to assume that a plausible intracellular target molecule(s) having a reactive
      sulfhydryl moiety might be regulated by the covalent attachment with BITC. In
      spite of no ability to affect the translocation of protein kinase C beta to the
      membrane, BITC probably modifies the electron transport system of cytochrome
      b558, consistent with the observation that BITC inhibited the substrate
      utilization. Pre-treatments of mouse skin with BITC significantly attenuated the
      TPA-enhanced hydrogen peroxide level, suggesting that BITC indeed acts as an
      inhibitor of O2- generation in mouse skin. A histological study also demonstrated
      that BITC inhibited TPA-induced leukocyte infiltration in the dermis. Because we
      have found several O2- generation inhibitors to be effective chemopreventors
      against mouse skin carcinogenesis, the modifying effect of the topical
      application of BITC on TPA-induced mouse skin tumor promotion was investigated.
      We demonstrated for the first time that the pre-treatment with BITC 40 min prior
      to each TPA treatment significantly inhibited the number of papillomas per mouse.
      In conclusion, the results from this study provided biological evidence that BITC
      has a potential to prevent inflammation-related carcinogenesis including skin
      cancer.

PMID- 14688022
TI  - The role of activated MEK-ERK pathway in quercetin-induced growth inhibition and
      apoptosis in A549 lung cancer cells.
AB  - Dietary phytochemicals have been shown to be protective against various types of
      cancers. However, the precise underlying protective mechanisms are poorly
      understood. In the present study, we report that treatment of A549 cells with
      quercetin resulted in a dose-dependent reduction in cell viability and DNA
      synthesis with the rate of apoptosis equivalent to 1.2 +/- 0.8, 6.3 +/- 0.9, 16.5
      +/- 1.5, 36.4 +/- 2.6 and 42.5 +/- 5.8% on treatment with 0.1% dimethylsulfoxide,
      14.5, 29.0, 43.5 and 58.0 micro M quercetin, respectively. Concomitantly,
      quercetin treatments led to a 1.1-, 1.1-, 2.5- and 3.5-fold increase in Bax.
      Similar elevations were also observed in Bad, which increased 1.1-, 2.1-, 2.2-
      and 2.3-fold, respectively, as compared with control. While Bcl-2 was decreased
      by 30%, Bcl-x(L) was elevated in a dose-dependent fashion. Quercetin also induced
      the cleavage of caspase-3, caspase-7 and PARP (poly ADP-ribose polymerase). While
      Akt-1 and phosphorylated Akt-1 were inhibited, the extracellular signal-regulated
      kinase (ERK) was phosphorylated following quercetin treatment in a dose-dependent
      fashion. Phosphorylation of ERK and c-Jun occurred at 3 h and was sustained over
      14 h. Phosphorylation of MEK1/2 was increased in concordance with ERK activation.
      Quercetin-induced phosphorylation of c-Jun N-terminal kinase (JNK) and cleavage
      of caspase-3 occurred 6 h after quercetin exposure and before cleavage of caspase
      7 and PARP was detected. Inhibition of MEK1/2 but not PI-3 kinase, p38 kinase or
      JNK abolished quercetin-induced phosphorylation of c-Jun, cleavage of caspase-3
      and -7, cleavage of PARP and apoptosis. Inhibition of caspase activation
      completely blocked quercetin-induced apoptosis. Expression of constitutively
      activated MEK1 in A549 cells led to activation of caspase-3 and apoptosis. The
      results suggest that in addition to inactivation of Akt-1 and alteration in the
      expression of the Bcl-2 family of proteins, activation of MEK-ERK is required for
      quercetin-induced apoptosis in A549 lung carcinoma cells.

PMID- 14688024
TI  - Delayed liver regeneration and increased susceptibility to chemical
      hepatocarcinogenesis in transgenic mice expressing a dominant-negative mutant of
      connexin32 only in the liver.
AB  - A growing body of evidence from in vitro studies indicates that gap junction
      proteins connexins may have a tumor-suppressor function. Our previous double
      transfection experiments on HeLa cells have shown that a dominant-negative mutant
      V139 M of connexin32 (Cx32) can abolish gap junctional intercellular
      communication (GJIC). To examine whether the same dominant-negative mutant of
      Cx32 inhibits GJIC between hepatocytes in vivo and thus modulates cell
      proliferation and susceptibility to hepatocarcinogenesis, we created transgenic
      mice with the mutant Cx32 gene driven by a liver-specific albumin promoter. These
      mice developed normally both before and after birth, and GJIC in their liver was
      diminished, as expected. No increase in incidence of spontaneous tumors of any
      site was observed in the transgenic mice. Rather unexpectedly, cell proliferation
      during liver regeneration after partial hepatectomy was retarded by 24 h in the
      transgenic mice compared with the wild-type mice. In contrast, the transgenic
      male mice were more susceptible to diethylnitrosamine-induced
      hepatocarcinogenesis, developing more liver tumors with shorter latency. These
      results show that GJIC can coordinate cell growth both positively and negatively
      in vivo, supporting the idea that GJIC is essential for maintenance of
      homeostasis.

PMID- 14688025
TI  - Mutation analysis of the BRAF, ARAF and RAF-1 genes in human colorectal
      adenocarcinomas.
AB  - Colorectal cancer is a multi-step process characterized by a sequence of genetic
      alterations in cell growth regulatory genes, such as the adenomatous polyposis
      coli, KRAS, p53 and DCC genes. In the present study mutation analysis was
      performed with SSCA/direct sequencing of the hot-spot regions in exons 11 and 15
      for the BRAF gene and exons 1-2 for the KRAS gene in 130 primary colorectal
      cancer tumors and correlated with clinico-pathological and mutational data. We
      also performed mutation analysis of the corresponding conserved regions in the
      ARAF and RAF-1 genes. Mutations in the BRAF and KRAS genes were found in 11.5 and
      40% of the tumors, respectively. One germline exonic and nine germline intronic
      genetic variants were found in the ARAF and RAF-1 genes. All of the BRAF
      mutations were located in the kinase domain of the conserved region 3 in exon 15
      of the BRAF gene. One novel somatic mutation was also identified in the BRAF
      gene. The majority of the BRAF mutations were found in colon compared with rectal
      tumors (P = 0.014). In agreement with others, a statistically significant
      correlation between BRAF mutations and microsatellite instability could be found.
      A negative correlation was also evident between mutations in the BRAF and KRAS
      genes, which supports earlier studies where somatic mutations in these genes are
      mutually exclusive. Collectively, our results provide support for the idea that
      activation of the MAP kinase pathway, especially via BRAF and KRAS mutations, is
      of critical importance for the development of colorectal cancer.

PMID- 14688026
TI  - Low dose induction of micronuclei by lindane.
AB  - Environmental contaminants possessing hormonal activity have long been suspected
      of playing a role in cancer causation. What is unclear is whether such agents
      elicit their effects through genotoxic and/or epigenetic mechanisms. gamma
      Hexachlorocyclohexane (gamma-HCH, lindane) was tested in the 10(-12)-10(-4) M
      range. Chromosomal damage in MCF-7 breast cells and PC-3 prostate cells was
      assessed using the cytokinesis block micronucleus assay. Micronuclei (MNi) were
      scored in 1000 binucleate cells per treatment. Cell viability and cell cycle
      kinetics were also assessed, along with immunocytochemical and quantitative gene
      expression analyses of CDKN1A (P21WAF1/CIP1), BCL-2 and BAX. Following 24 h
      treatment, lindane (10(-12)-10(-10) M) induced increases (up to 5-fold) in MNi in
      both cell lines. Increases in MNi occurred in the absence of DNA single-strand
      breaks or cytotoxicity and, compared with benzo[a]pyrene and 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine, at low concentrations. Lindane induced more MNi
      than the alpha or beta stereoisomers of HCH. Low dose lindane (10(-12)-10(-10) M)
      significantly elevated the percentage of MCF-7 cells staining positive for Bcl-2
      and of PC-3 cells staining positive for Bax. Only high dose lindane (10(-4) M)
      disrupted cell cycle kinetics with increases in percentage of cells in G1 and
      decreases in percentage of cells in G2/M. Despite a comparable high dose lindane
      induction of cell cycle arrest, marked increases in expression of P21WAF1/CIP1
      were observed only in MCF-7 cells, although in PC-3 cells a significant increase
      (P < 0.0005) in the percentage of cells staining positive for p21Waf1/Cip1 was
      seen. These results suggest that 'environmental' concentrations of lindane can
      induce a number of subtle alterations in breast and prostate cells in the absence
      of cytotoxicity.

PMID- 14688027
TI  - Id-1 expression induces androgen-independent prostate cancer cell growth through
      activation of epidermal growth factor receptor (EGF-R).
AB  - The failure of prostate cancer treatment is largely due to the development of
      androgen independence, since the androgen depletion therapy remains the front
      line option for this cancer. Previously, we reported that over-expression of the
      helix-loop-helix protein Id-1 was associated with progression of prostate cancer
      and ectopic expression of Id-1 induced serum-independent proliferation in
      prostate cancer cells. In the present study, we investigated if exogenous Id-1
      expression in the androgen sensitive LNCaP cells had any effect on androgen
      dependent cell growth and studied the molecular mechanisms involved. Using stable
      Id-1 transfectants, we found that expression of Id-1 was able to reduce androgen
      stimulated growth and S phase fraction of the cell cycle in LNCaP cells,
      indicating that Id-1 may be involved in the development of androgen independence
      in these cells. The Id-1-induced androgen-independent prostate cancer cell growth
      was correlated with up-regulation of EGF-R (epidermal growth factor-receptor) and
      PSA (prostate specific antigen) expression, as confirmed by western blotting
      analysis and luciferase assays. In contrast, down-regulation of Id-1 in androgen
      independent DU145 cells by its antisense oligonucleotides resulted in suppression
      of EGF-R expression at both transcriptional and protein levels. In addition, the
      results from immunohistochemistry study showed that Id-1 expression was
      significantly elevated in hormone refractory prostate cancer tissues when
      compared with the hormone-dependent tumours. Our results suggest that up
      regulation of Id-1 in prostate cancer cells may be one of the mechanisms
      responsible for developing androgen independence and this process may be
      regulated through induction of EGF-R expression. Inactivation of Id-1 may provide
      a potential therapeutic strategy leading to inhibition of androgen-independent
      prostate cancer cell growth.

PMID- 14688028
TI  - Oxidative stress in cancer prone xeroderma pigmentosum fibroblasts. Real-time and
      single cell monitoring of superoxide and nitric oxide production with
      microelectrodes.
AB  - Sun exposure is clearly implicated in premature skin ageing and neoplastic
      development. These features are exacerbated in patients with Xeroderma
      pigmentosum (XP), a hereditary disease associated at the cellular level with DNA
      repair defects and a low catalase activity. The implications of oxidative stress
      in the defects and cancer proneness of XP skin cells (keratinocytes, fibroblasts)
      are multiple and remain unclear. They were investigated here at the level of a
      single fibroblast by an electrochemical method based on microelectrodes we have
      developed previously. These microelectrodes permit a real-time quantification and
      identification of superoxide and nitric oxide derivatives (H2O2, ONOO-, NO*, NO2
      ) released by a living cell following its stimulation. Then, the oxidative bursts
      produced by fibroblasts from normal strains were compared with those of
      fibroblasts from several XP group A (XPA) and XP group D (XPD) strains. All XPA
      and XPD strains provided responses of higher amplitude and duration than
      controls. The XP specific oxidative response could not be correlated with DNA
      repair ability since the transduction of XPD strains with the wild-type XPD gene
      did not modify their production of reactive oxygen and nitrogen species. The
      nature of these species was investigated and revealed that cancer prone XPD
      fibroblasts produced higher amounts of O2*- and H2O2 and lower amounts of NO* and
      ONOO than normal fibroblasts.

PMID- 14688029
TI  - Methylated DNA-binding protein 2 antisense inhibitors suppress tumourigenesis of
      human cancer cell lines in vitro and in vivo.
AB  - Methylated DNA-binding protein 2 (MBD2) has been proposed to function both as a
      silencer of methylated genes and as a DNA demethylase. Our previous data
      indicated that knockdown of MBD2 inhibited tumourigenesis of human cancer lines
      and MBD2-deficient mice were recently shown to be resistant to intestinal
      tumourigenesis. MBD2 is an attractive anticancer target since MBD2-deficient mice
      were previously shown to be viable and fertile and knockdown of MBD2 was reported
      to have no effect on cellular growth parameters of non-transformed cells. In this
      paper we test the hypothesis that pharmacological inhibition of MBD2 inhibits
      cancer growth in vivo using human tumour lines implanted in mice as a model. We
      develop sequence-specific antisense inhibitors of MBD2 and we show that these
      agents inhibit anchorage-independent growth of human lung (A549) and colorectal
      (HCT116) cancer cell lines in vitro and tumourigenic growth of human cancer cell
      xenografts in vivo. MBD2 antisense oligonucleotide does not inhibit the growth of
      normal and transformed cell lines and does not alter cell cycle parameters in
      vitro and does not exhibit overt toxicity in vivo in comparison with a scrambled
      control oligonucleotide, as determined by measuring body mass, blood cell
      parameters and liver and kidney enzymes. Our data provide a proof of principle
      that MBD2 is a new anticancer target and that pharmacological inhibition of MBD2
      by agents such as the antisense inhibitors described in this paper is a potential
      new anticancer therapy, which in contrast to the vast majority of current
      approaches does not target normal progression of the cell cycle.

PMID- 14688030
TI  - o-Nitrotoluene-induced large intestinal tumors in B6C3F1 mice model human colon
      cancer in their molecular pathogenesis.
AB  - In the previous 500 2-year chemical bioassays within the National Toxicology
      Program, large intestinal tumors (cecal carcinomas) related to chemical exposure
      have not been observed in B6C3F1 mice. The recently completed o-nitrotoluene
      study provided the first cecal tumor response and an opportunity to evaluate the
      morphology and molecular profile of oncogenes and tumor suppressor genes that are
      relevant to humans. Morphologically, the carcinomas were gland-forming tumors
      lined by tall columnar epithelial cells that were positive for cytokeratin 20 and
      negative for cytokeratin 7. Using immunohistochemistry beta-catenin (encoded by
      Catnb) protein accumulation was detected in 80% (8/10) of the cecal carcinomas,
      while increased cyclin D1 and p53 protein expression was detected in 73% (8/11),
      respectively. There was no difference in adenomatous polyposis protein expression
      between normal colon and cecal carcinomas. All tumors examined exhibited
      mutations in exon 2 (corresponds to exon 3 in humans) in the Catnb gene.
      Mutations in p53 were identified in nine of 11 carcinomas, and all were in exon
      7. Analysis of the K-ras gene revealed mutations in 82% (9/11) of carcinomas; all
      had specific G --> T transversions (Gly --> Val) at codons 10 or 12. The
      alterations in cancer genes and proteins found in the mouse large intestinal
      tumors included mutations that activate signal transduction pathways (K-ras and
      Catnb) and changes that disrupt the cell-cycle and bypass G(1) arrest (p53,
      cyclin D1). These alterations, which are hallmarks of human colon cancer,
      probably contributed to the pathogenesis of the large intestinal carcinomas in
      mice following o-nitrotoluene exposure.

PMID- 14688031
TI  - Ozone exposure decreases the effect of a deep inhalation on forced expiratory
      flow in normal subjects.
AB  - Sixteen healthy nonsmoking subjects (7 women), 21-49 yr old, were exposed in a
      climate chamber to either clean air or 300 parts/billion ozone on 4 days for 5 h
      each day. Before each exposure, the subjects had been pretreated with either
      oxidants (fish oil) or antioxidants (multivitamins). The study design was double
      blind crossover with randomized allocation to the exposure regime. Full and
      partial flow-volume curves were recorded in the morning and before and during a
      histamine provocation at the end of the day. Nasal cavity volume and inflammatory
      markers in nasal lavage fluid were also measured. Compared with air, ozone
      exposure decreased peak expiratory flow, forced expiratory volume in 1 s, and
      forced vital capacity (FVC), with no significant effect from the pretreatment
      regimens. Ozone decreased the ratio of maximal to partial flow at 40% FVC by 0.08
      +/- 0.03 (mean +/- SE, analysis of variance: P = 0.018) and at 30% FVC by 0.10 +/
      0.05 (P = 0.070). Ozone exposure did not significantly increase bronchial
      responsiveness, but, after treatment with fish oil, partial flows decreased more
      than after vitamins during the histamine test, without changing the maximal-to
      partial flow ratio. The decreased effect of a deep inhalation after ozone
      exposure can be explained by changes in airway hysteresis relative to parenchymal
      hysteresis, due either to ozone-induced airway inflammation or to less deep
      inspiration after ozone, not significantly influenced by multivitamins or fish
      oil.

PMID- 14688032
TI  - Simultaneous control of hand displacements and rotations in orientation-matching
      experiments.
AB  - In reach-to-grasp movements, the interaction between the hand changes in position
      and those in orientation is poorly understood. A theoretical approach previously
      proposed (Torres EB and Zipser D. J Neurophysiol 88: 1-13, 2002) assumes that
      motion strategies are resolved in space independently from the temporal dynamics
      of the motion and predicts the coarticulation of the hand transport and rotation
      along the path. The model implies that this simultaneous control is independent
      of variations in speed and initial posture and required matching orientation.
      This paper presents experimental data from human subjects that confirm the
      model's predictions in the context of realistic, unconstrained, orientation
      matching motions. Speed independence is quantified in the similarity of the
      postural and endpoint position-orientation paths obtained under three different
      speeds. Significant differences in hand and joint kinematics are shown in
      response to changes in initial posture and target orientation. The robustness of
      coarticulation under all three experimental conditions supports the idea of an
      intermediate stage that resolves the geometry of the motion independent of its
      temporal dynamics.

PMID- 14688033
TI  - Surfactant from diving aquatic mammals.
AB  - Diving mammals that descend to depths of 50-70 m or greater fully collapse the
      gas exchanging portions of their lungs and then reexpand these areas with ascent.
      To investigate whether these animals may have evolved a uniquely developed
      surfactant system to facilitate repetitive alveolar collapse and expansion, we
      have analyzed surfactant in bronchoalveolar lavage fluid (BAL) obtained from nine
      pinnipeds and from pigs and humans. In contrast to BAL from terrestrial mammals,
      BAL from pinnipeds has a higher concentration of phospholipid and relatively more
      fluidic phosphatidylcholine molecular species, perhaps to facilitate rapid
      spreading during alveolar reexpansion. Normalized concentrations of hydrophobic
      surfactant proteins B and C were not significantly different among pinnipeds and
      terrestrial mammals by immunologic assay, but separation of proteins by gel
      electrophoresis indicated a greater content of surfactant protein B in elephant
      seal surfactant than in human surfactant. Remarkably, surfactant from the deepest
      diving pinnipeds produced moderately elevated in vitro minimum surface tension
      measurements, a finding not explained by the presence of protein or neutral lipid
      inhibitors. Further study of the composition and function of pinniped surfactants
      may contribute to the design of optimized therapeutic surfactants.

PMID- 14688034
TI  - Neuromuscular changes for hopping on a range of damped surfaces.
AB  - Humans hopping and running on elastic and damped surfaces maintain similar center
      of-mass dynamics by adjusting stance leg mechanics. We tested the hypothesis that
      the leg transitions from acting like an energy-conserving spring on elastic
      surfaces to a power-producing actuator on damped surfaces during hopping due to
      changes in ankle mechanics. To test this hypothesis, we collected surface
      electromyography, video kinematics, and ground reaction force while eight male
      subjects (body mass: 76.2 +/- 1.7 kg) hopped in place on a range of damped
      surfaces. On the most damped surface, most of the mechanical work done by the leg
      appeared at the ankle (52%), whereas 23 and 25% appeared at the knee and hip,
      respectively. Hoppers extended all three joints during takeoff further than they
      flexed during landing and thereby did more net positive work on more heavily
      damped surfaces. Also, all three joints reached peak flexion sooner after
      touchdown on more heavily damped surfaces. Consequently, peak moment occurred
      during joint extension rather than at peak flexion as on elastic surfaces. These
      strategies caused the positive work during extension to exceed the negative work
      during flexion to a greater extent on more heavily damped surfaces. At the muscle
      level, surface EMG increased by 50-440% in ankle and knee extensors as surface
      damping increased to compensate for greater surface energy dissipation. Our
      findings, and those of previous studies of hopping on elastic surfaces, show that
      the ankle joint is the key determinant of both springlike and actuator-like leg
      mechanics during hopping in place.

PMID- 14688035
TI  - Temperature regulation during rest and exercise in the cold in premenarcheal and
      menarcheal girls.
AB  - Temperature regulation during exercise in the cold was examined in 13 adolescent
      female individuals, aged 13-18 yr. Six girls with established menstrual cycles
      comprised the eumenorrheic menarcheal (EM) group, and seven nonmenstruating girls
      comprised the premenarcheal (PM) group. During the first visit, maximal oxygen
      consumption (Vo(2 max)), height, weight, and percent body fat were measured. The
      second visit included a determination of metabolic rate in thermoneutrality (21
      degrees C), consisting of a 10-min rest period and 20 min of cycling (30% of Vo(2
      max)), and a cold test (5 degrees C, 40% humidity, <0.3 m/s air velocity)
      involving a 20-min rest period and 40 min of cycling (30% of Vo(2 max)). Subjects
      in the EM group were tested twice in the chamber: once during the follicular and
      once during the luteal phase. Heat production per kilogram in thermoneutrality
      and in the cold was significantly (P < 0.05) higher in the PM compared with the
      EM girls. However, the PM girls had a significantly (P < 0.05) lower core
      temperature in the cold than the EM group. PM girls also had a significantly
      higher body surface area-to-mass ratio compared with the EM girls. Although
      percent body fat between groups was not significantly different, within the PM
      group percent body fat explained 79% (P < 0.01) of the variance in the decrease
      of core temperature. There were no menstrual phase-related differences in
      temperature regulation in either the thermoneutral or cold environment. In
      conclusion, menstrual phase does not influence temperature regulation in female
      individuals during adolescence. EM girls had lower metabolic heat production but
      maintained their core temperature more effectively in the cold than did the PM
      girls. This thermoregulatory difference between PM and EM girls is mainly a
      function of geometric differences with maturation-related peripheral
      vasoconstrictive differences maybe limiting the effectiveness of the mechanism of
      increased heat storage in younger female individuals.

PMID- 14688036
TI  - Continuous tracheal gas insufflation during partial liquid ventilation in
      juvenile rabbits with acute lung injury.
AB  - To examine the hypothesis that combined treatment with tracheal gas insufflation
      (TGI) and partial liquid ventilation (PLV) may improve pulmonary outcome relative
      to either treatment alone in acute lung injury (ALI), saline lavage lung injury
      was induced in 24 anesthetized, ventilated juvenile rabbits that were then
      randomly assigned to receive (n = 6/group) 1) conventional mechanical ventilation
      (CMV) alone, 2) continuous TGI at 0.5 l/min, 3) PLV with perfluorochemical
      liquid, and 4) combined TGI and PLV (TGI + PLV), and subsequently ventilated with
      minimized pressures and tidal volume (Vt) to keep arterial Po(2) (Pa(O(2))) >100
      Torr and arterial Pco(2) (Pa(CO(2))) at 45-60 Torr for 4 h. Gas exchange, lung
      mechanics, myeloperoxidase, IL-8, and histomorphometry [including expansion index
      (EI)] were assessed. The CMV group showed no improvement in lung mechanics and
      gas exchange; all treated groups had significant increases in compliance,
      Pa(O(2)), ventilation efficacy index (VEI), and EI, and decreases in PaCO(2),
      oxygenation index, physiological dead space-to-Vt ratio (Vd/Vt), myeloperoxidase,
      and IL-8, relative to the CMV group. TGI resulted in lower peak inspiratory
      pressure, Vt, Vd/Vt, and greater VEI vs. PLV group; PLV resulted in greater
      compliance, Pa(O(2)), and EI vs. TGI. TGI + PLV resulted in decreased peak
      inspiratory pressure, Vt, Vd/Vt, and increased VEI compared with TGI, improved
      compliance and EI compared with PLV, and a further increase in Pa(O(2)) and
      oxygenation index and a decrease in PaCO(2) vs. either treatment alone. These
      results indicate that combined treatment of TGI and PLV results in improved
      pulmonary outcome than either treatment alone in this animal model of ALI.

PMID- 14688037
TI  - Distribution dynamics of perfluorocarbon delivery to the lungs: an intact rabbit
      model.
AB  - Motivated by the goal of understanding how to most homogeneously fill the lungs
      with perfluorocarbon for liquid ventilation, we investigate the transport of
      liquid instilled into the lungs using an intact rabbit model. Perfluorocarbon is
      instilled into the trachea of the ventilated animal. Radiographic images of the
      perfluorocarbon distribution are obtained at a rate of 30 frames/s during the
      filling process. Image analysis is used to quantify the liquid distribution
      (center of mass, spatial standard deviation, skewness, kurtosis, and indicators
      of homogeneity) as time progresses. We compare the distribution dynamics in
      supine animals to those in upright animals for three constant infusion rates of
      perfluorocarbon: 15, 40, and 60 ml/min. It is found that formation of liquid
      plugs in large airways, which is affected by posture and infusion rate, can
      result in a more homogeneous liquid distribution than gravity drainage alone. The
      supine posture resulted in more homogeneous filling of the lungs than did upright
      posture, in which the lungs tend to fill in the inferior regions first. Faster
      instillation of perfluorocarbon results in liquid plugs forming in large airways
      and, consequently, more uniform distribution of perfluorocarbon than slower
      instillation rates in the upright animals.

PMID- 14688038
TI  - BB-3497, a peptide deformylase inhibitor, is active against Mycobacterium
      tuberculosis.

PMID- 14688039
TI  - National surveillance of species distribution in blood isolates of Candida
      species in Japan and their susceptibility to six antifungal agents including
      voriconazole and micafungin.
AB  - OBJECTIVES: The aim of this study was to evaluate species distribution and
      antifungal susceptibility of Candida blood isolates in Japan. METHODS: In a 1
      year surveillance programme, 535 Candida blood isolates were collected.
      Identification of species was followed by examination with the broth
      microdilution method, as described in NCCLS M27-A2, of antifungal susceptibility
      to six agents, including voriconazole and micafungin, with readings after 24 and
      48 h of incubation. RESULTS: The overall species distribution was: 41% Candida
      albicans, 23% Candida parapsilosis, 18% Candida glabrata, 12% Candida tropicalis
      and 2% Candida krusei. The concentrations of fluconazole necessary to inhibit 90%
      of the isolates (MIC(90)) at 24/48 h were 0.25/1 mg/L for C. albicans, 0.5/2 mg/L
      for C. parapsilosis, 4/32 mg/L for C. glabrata and 4/>128 mg/L for C. tropicalis.
      Percentages of fluconazole resistance were 1.8% for C. albicans, 0.8% for C.
      parapsilosis, 5.2% for C. glabrata and 3.2% for C. tropicalis, taking the
      tendency of trailing growth of C. tropicalis into account. MIC(90) of
      voriconazole was 0.5 mg/L, although 35% of isolates less susceptible (>/=16 mg/L)
      to fluconazole showed resistance (>/=2 mg/L). Micafungin was very active against
      all species (MIC(90), 0.03 mg/L) except for C. parapsilosis (MIC(90), 2 mg/L).
      CONCLUSIONS: These data suggest that, in Japan, the species distribution of
      Candida bloodstream infections and the fluconazole resistance rate are similar to
      those reported previously in North America and Europe. Voriconazole and
      micafungin appear to have strong in vitro activity against Candida blood
      isolates, although continuing surveillance and further clinical research are
      needed.

PMID- 14688040
TI  - Molecular characterization of hospital vancomycin-resistant Enterococcus faecalis
      isolated in Slovakia.

PMID- 14688041
TI  - ESBL-producing multidrug-resistant Providencia stuartii infections in a
      university hospital.
AB  - OBJECTIVES: To investigate the epidemiological and clinical findings of extended
      spectrum beta-lactamase (ESBL)-producing Providencia stuartii infections in a
      large Italian university hospital. PATIENTS AND METHODS: All consecutive episodes
      of P. stuartii infection that occurred during 1999-2002 were included in the
      study. For each patient, we recorded the area of hospitalization and drug
      susceptibility of the P. stuartii strains. Patients with ESBL-producing P.
      stuartii infection were considered cases and those with non-ESBL-producing P.
      stuartii infection were used as controls. RESULTS: One hundred and sixteen (52%)
      out of 223 P. stuartii strains collected during the study period were found to be
      ESBL-producing. On the basis of PCR and DNA sequencing experiments, TEM-52 was
      identified in 87% of isolates and TEM-72 in 13%. All ESBL-producing P. stuartii
      infections were nosocomially acquired. The prevalence increased from 31% of P.
      stuartii infections in 1999 to 62% in 2002 (P = 0.04). All 116 strains were
      classified as ESBL-producing multidrug-resistant P. stuartii, since 88% of the
      isolates were cross-resistant to ciprofloxacin and amikacin and the other 12%
      were cross-resistant to ciprofloxacin and gentamicin. At logistic regression
      analysis, advanced age (P < 0.001), previous hospitalization (P < 0.01),
      neoplastic disease (P < 0.001) and previous antibiotic therapy (P < 0.001) were
      independent risk factors for the development of ESBL-producing infections.
      CONCLUSIONS: This 4 year surveillance of Providencia complaints clearly indicates
      that infections caused by ESBL-producing multidrug-resistant P. stuartii are an
      emerging problem.

PMID- 14688042
TI  - Multiple effects of green tea catechin on the antifungal activity of antimycotics
      against Candida albicans.
AB  - OBJECTIVES: The susceptibility of Candida albicans to catechin under varying pH
      conditions and the synergism of the combination of catechin and antimycotics were
      evaluated. METHOD: Antifungal activity was determined by broth dilution and
      calculation of cfu. RESULTS: The antifungal activity of catechin was pH
      dependent. The concentration of epigallocatechin gallate (EGCg) causing 90%
      growth inhibition of tested strains of C. albicans was 2000 mg/L at pH 6.0, 500
      1000 mg/L at pH 6.5 and 15.6-250 mg/L at pH 7.0. Among catechins, pyrogallol
      catechin showed stronger antifungal activity against C. albicans than catechol
      catechin. The addition of 6.25-25 or 3.12-12.5 mg/L EGCg to amphotericin B 0.125
      or 0.25 mg/L (below MIC) at pH 7.0 resulted in enhancement, respectively, of the
      antifungal effect of amphotericin B against amphotericin B-susceptible or 
      resistant C. albicans. Combined treatment with 3.12-12.5 mg/L EGCg plus
      amphotericin B 0.5 mg/L (below MIC) markedly decreased the growth of amphotericin
      B-resistant C. albicans. When fluconazole-susceptible C. albicans was treated
      with 25-50 mg/L EGCg and fluconazole 0.125-0.25 mg/L (below MIC), its growth was
      inhibited by 93.0%-99.4% compared with its growth in the presence of fluconazole
      alone. The combined use of 12.5 mg/L EGCg and fluconazole 10-50 mg/L (below MIC)
      inhibited the growth of fluconazole-resistant C. albicans by 98.5%-99.7%.
      CONCLUSIONS: These results indicate that EGCg enhances the antifungal effect of
      amphotericin B or fluconazole against antimycotic-susceptible and -resistant C.
      albicans. Combined treatment with catechin allows the use of lower doses of
      antimycotics and induces multiple antifungal effects. It is hoped that this may
      help to avoid the side effects of antimycotics.

PMID- 14688043
TI  - Detection of TEM-52 in Salmonella enterica serovar Enteritidis isolated in
      Scotland.

PMID- 14688044
TI  - Rifampicin resistance and its fitness cost in Enterococcus faecium.
AB  - OBJECTIVES: The genetic basis of rifampicin resistance and the associated fitness
      cost in Enterococcus faecium were investigated. METHODS: Twelve spontaneous
      rifampicin-resistant E. faecium mutants were selected from four parent strains
      recently isolated from porcine faecal material. The DNA sequence of the complete
      rpoB gene from the parent strains and of nucleotides -189 to +1785 from the
      mutants was determined from PCR amplicons. The fitness of the mutants was
      assessed by determining growth rate, by direct growth competition and by the
      ability of some of the mutants to survive in the pig intestine. RESULTS: The rpoB
      genes of the parent strains diverged from each other by 1-10% and each encoded
      proteins that were 1208 amino acids in length. All mutants had a single amino
      acid substitution in the region implicated in rifampicin resistance in other
      organisms. Six mutants carried the substitution H489Y/Q, two mutants carried the
      substitution R492H, one mutant carried the substitution Q480H, two mutants
      carried the substitutions S494L and V224I, and one mutant carried the
      substitutions G485D and V224I. Per generation fitness costs of the mutants ranged
      from a gain of 2.5% to a cost of 10%. Mutants with the substitution H489Y/Q were
      the most fit, whereas the double mutants were the least fit. The mutant with the
      substitution H489Q was able to survive in the pig gut for 12 days. There was some
      correlation between the rifampicin MIC and fitness cost, with higher MICs being
      associated with higher fitness costs. CONCLUSIONS: Substitutions in RpoB are
      associated with rifampicin resistance in E. faecium. The fitness cost of
      resistance is variable and can sometimes be absent.

PMID- 14688045
TI  - Design and synthesis of antituberculars: preparation and evaluation against
      Mycobacterium tuberculosis of an isoniazid Schiff base.
AB  - OBJECTIVES: Enzymatic acetylation of the antitubercular isoniazid (INH) by N
      acetyltransferase represents a major metabolic pathway for INH in human beings.
      Acetylation greatly reduces the therapeutic activity of the drug, resulting in
      underdosing, decreased bioavailability and acquired INH resistance. Chemical
      modification of INH with a functional group that blocks acetylation, while
      maintaining strong antimycobacterial action, may improve clinical outcomes and
      help reduce the rise of INH resistance. The goal of this study was to probe
      activities, toxicity and bioavailability of an investigational compound prepared
      by this chemical modification. METHODS: The investigational compound was chosen
      from a cohort of lipophilic antitubercular INH Schiff bases based on its strong
      activity in primary assays. The compound was evaluated in vitro, in vivo in mice,
      in mutagenicity tests and in rats for bioavailability. RESULTS: The INH Schiff
      base acts against both intracellular and extracellular organisms in vitro, with a
      wide range between active and cytotoxic concentrations. The material is active
      against non-tubercular mycobacteria. The INH Schiff base is non-mutagenic in the
      Ames test and has excellent bioavailability in Sprague-Dawley rats, achieving
      early peak plasma concentrations approximately three orders of magnitude above
      its MIC when administered orally. In tuberculosis-infected mice the compound is
      well tolerated and in a 4 week study provides 3 log cfu reduction in spleens and
      4 log cfu reduction in lungs. CONCLUSION: The results demonstrate that
      investigational compounds in which N-acetylation of INH is blocked by chemical
      modification can display strong activity, low toxicity and excellent
      bioavailability, making them suitable for further exploration.

PMID- 14688046
TI  - Drug resistance genes and trailing growth in Candida albicans isolates.
AB  - OBJECTIVES: To investigate possible molecular mechanisms of azole resistance
      among fluconazole-susceptible bloodstream isolates of Candida albicans that
      displayed the trailing growth phenomenon, and to compare these isolates with
      bloodstream and mucosal isolates that showed reduced susceptibilities to
      fluconazole. METHODS: Twelve C. albicans isolates-seven trailing and five
      susceptible dose dependent (SDD) or resistant (R)-were screened for ERG11
      mutations by DNA sequencing and quantification of ERG11, CDR1 and MDR1 expression
      by RT-PCR using the LightCycler high-speed PCR system. RESULTS: SDD and R
      isolates possessed more homozygous ERG11 mutations than did the trailing
      isolates. Two of these, V404I and V509M, have not been described previously and
      were found exclusively in fluconazole SDD and R isolates. Quantification of ERG11
      expression revealed that both trailing and SDD and R isolates were capable of
      ERG11 up-regulation in response to fluconazole, although the SDD and R isolates
      showed maximal up-regulation at higher fluconazole concentrations. Quantification
      of CDR1 and MDR1 revealed that all isolates, regardless of in vitro fluconazole
      response, were capable of CDR1 and MDR1 up-regulation following fluconazole
      exposure. Furthermore, the SDD and R isolates expressed higher constitutive
      levels of CDR1 and MDR1 or CDR1, respectively, in the absence of drug compared
      with trailing isolates. CONCLUSIONS: Trailing isolates, although susceptible to
      fluconazole, express the same molecular mechanisms as SDD and R isolates
      following fluconazole exposure but regulate them differently.

PMID- 14688047
TI  - A new millennium conundrum: how to use a powerful class of influenza anti
      neuraminidase drugs (NAIs) in the community.
AB  - Influenza A and B viruses cause serious medical problems and social disruption
      every year in particular countries of the world. The virus is notoriously fickle
      and may attack citizens in say two adjacent countries but not the third. More
      rarely a global pandemic virus emerges causing millions of deaths worldwide. The
      SARS outbreak has illuminated weaknesses in planning for sudden outbreaks of
      disease in a modern society and in particular how panic can grip and cause
      intense economic disruption. Many communities in the world are neither prepared
      for a global pandemic nor a very acute epidemic of influenza. The neuraminidase
      inhibitors (NAIs) are a new class of antiviral drug targeting a viral influenza
      enzyme, the neuraminidase, which acts both to facilitate virus infection of cells
      by clearing a passage through otherwise protective respiratory fluids and also by
      helping release of the virus by cutting the chemical umbilical cord which links
      up the virus to the infected cell. Extensive laboratory studies of the two
      molecules zanamivir and oseltamivir have shown that they block all influenza A
      and B viruses yet tested and would, in theory, even inhibit the 1918 pandemic
      virus. Both drugs can be used prophylactically to prevent spread of infection in
      families and communities where 80-90% protection has been documented. The
      therapeutic effects are also strong in adults and children abbreviating
      infection, reducing quantities of excreted virus and reducing antibiotic
      prescriptions. The drugs have to be taken within 48 h of the onset of symptoms.
      Drug resistance is not a problem at present because although such mutants occur
      the mutants are compromised and are less virulent than their drug-sensitive
      parents and they spread less easily. The two drugs could be stockpiled to prepare
      for an influenza pandemic but, importantly, clinical and scientific experience
      need to be gained by using these inhibitors in the yearly conflagrations of
      epidemic influenza, which unchecked do great harm to our communities.

PMID- 14688048
TI  - Mutant prevention concentration of nalidixic acid, ciprofloxacin, clinafloxacin,
      levofloxacin, norfloxacin, ofloxacin, sparfloxacin or trovafloxacin for
      Escherichia coli under different growth conditions.
AB  - OBJECTIVES: We used two different strains of Escherichia coli, E.coli ATCC 25922
      and a recent urinary isolate from a clinical sample, to investigate in vitro how
      the MIC and mutant prevention concentration (MPC) are affected by different
      temperatures (37 or 20 degrees C) or oxygen tension (aerobic or anaerobic
      atmosphere; MIC, MIC(an); MPC, MPC(an)). MATERIALS AND METHODS: MIC and MPC for
      E.coli ATCC 25922 and the clinical isolate were determined on agar containing
      ciprofloxacin or levofloxacin, and for the ATCC strain on agar supplemented with
      nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin or
      clinafloxacin. RESULTS: Results for the ATCC strain and the clinical strain for
      ciprofloxacin or levofloxacin were similar. The MPC values for E.coli ATCC 25922
      were 2 x MIC (trovafloxacin), 4 x MIC (ciprofloxacin, norfloxacin, ofloxacin), 8
      x MIC (clinafloxacin, levofloxacin), 16 x MIC (sparfloxacin) and 32 x MIC
      (nalidixic acid) at 37 degrees C and under aerobic conditions. Generally, a 37
      degrees C aerobic atmosphere was associated with the highest MPC values. As an
      exception, both the MIC and the MPC of ciprofloxacin were higher under anaerobic
      versus aerobic conditions (MIC(an) approximately 8 x MIC; MPC(an) = 4 x MPC) for
      both E.coli isolates. Irrespective of the quinolone or growth conditions, the MIC
      for mutants was 1-256 x wild-type MIC. Calculated from published serum half-lives
      and the MPC values from this study, a putative selection period, in which
      resistant mutants might be selected, was calculated to be 14 h for nalidixic
      acid, 16 h for norfloxacin and ciprofloxacin, 28 h for ofloxacin, 30 h for
      trovafloxacin, 35 h for levofloxacin, 40 h for clinafloxacin, and 120 h for
      sparfloxacin. CONCLUSIONS: As calculated from our model in respect to the length
      of the selection period, long serum half-lives of recently developed compounds
      could not be compensated for by a more favourable activity in terms of MPC.
      Higher concentrations of ciprofloxacin may be required under an anaerobic
      atmosphere to prevent the emergence of resistant mutants among 10(10) cfu.

PMID- 14688049
TI  - Antibiotic prophylaxis, body piercing and infective endocarditis.
AB  - Infective endocarditis (IE) is associated with a high degree of morbidity and
      mortality and generally presents in patients with altered and abnormal heart
      architecture combined with exposure to bacteria through trauma and other
      potentially high-risk activities, including body piercing. Modern social
      behaviour has resulted in increased popularity of the practice of body piercing,
      particularly amongst the adolescent population and there has been a marked rise
      of cases of IE directly attributable to this practice. In this article we wish to
      examine the aetiology of such cases reported in the literature, with particular
      emphasis on causal organism, as well as to discuss the role of antibiotic
      prophylaxis and awareness in such at-risk patients within the primary care
      community.

PMID- 14688050
TI  - Trends in the treatment of orthopaedic prosthetic infections.
AB  - The most commonly used therapy for prosthetic joint infection is a two-stage
      prosthetic exchange separated by 6 weeks of intravenous antibiotic therapy. This
      often results in long periods of hospitalization, morbidity, severe functional
      impairment and sometimes increased mortality. Therefore novel and challenging
      therapeutic approaches have been attempted, particularly in hip prosthetic
      infection. This includes, whenever possible, according to the type of
      microorganism, antibacterial susceptibility and clinical presentation (including
      age and comorbidities): (i) less aggressive surgical techniques (debridement and
      prosthesis retention, or re-implantation with a single-stage exchange
      arthroplasty); and (ii) antibiotic combinations active against biofilm-associated
      bacteria, including rifampicin (particularly with quinolones) with excellent bio
      availability which allow prolonged and efficient oral therapy.

PMID- 14688052
TI  - Available clinical markers of treatment outcome integrated in mathematical models
      to guide therapy in HIV infection.
AB  - Because treatment failure in many HIV-infected persons may be due to multiple
      causes, including resistance to antiretroviral agents, it is important to better
      tailor drug therapy to individual patients. This improvement requires the
      prediction of treatment outcome from baseline immunological or virological
      factors, and from results of resistance tests. Here, we review briefly the
      available clinical factors that have an impact on therapy outcome, and discuss
      the role of a predictive modelling approach integrating these factors proposed in
      a previous work. Mathematical and statistical models could become essential tools
      to address questions that are difficult to study clinically and experimentally,
      thereby guiding decisions in the choice of individualized drug regimens.

PMID- 14688051
TI  - Release of gentamicin and vancomycin from temporary human hip spacers in two
      stage revision of infected arthroplasty.
AB  - AIM: Evaluation of the delivery of gentamicin and vancomycin from
      polymethylmethacrylate (PMMA) spacers before and after implantation for the
      treatment of total hip replacement infections. METHODS: Twenty industrially
      produced spacers containing gentamicin (1.9%) were utilized. Vancomycin (2.5%)
      mixed with PMMA cement was used to fill holes drilled in the cement of 14 of the
      20 spacers immediately before implantation. The spacers were removed from 20
      patients 3-6 months after implantation and then immersed in phosphate buffer at
      37 degrees C for 10 days. Antibiotic concentrations were determined by
      fluorescence polarization immunoassay. RESULTS: Gentamicin and vancomycin were
      still present in all the spacers removed from the patients. The release of
      gentamicin alone and in combination with vancomycin was in the range 0.05%-0.4%
      of the initial amount present, whereas the release of vancomycin was in the range
      0.8%-3.3%. The release kinetics showed a similar pattern for both drugs. After a
      high initial release of drug, a reduced, but constant, elution was observed over
      the next few days. CONCLUSIONS: The delivery of gentamicin and vancomycin from
      PMMA cement was high initially, with sustained release over several months.
      Incorporation of vancomycin into the surface of the spacers permitted spacers to
      be prepared with multiple antibiotics present and without adversely affecting the
      release kinetics of the agents. The gentamicin-vancomycin combination shows
      potential for the treatment of infection following total hip replacement in
      specific patients.

PMID- 14688053
TI  - Comparative evaluation of three computerized algorithms for prediction of
      antiretroviral susceptibility from HIV type 1 genotype.
AB  - OBJECTIVES: To compare three methods for using HIV-1 genotype to predict
      antiretroviral drug susceptibility. METHODS: We applied three genotypic
      interpretation algorithms to 478 reverse transcriptase (RT) and 410 protease
      sequences for which phenotypic data were available. Sequences were obtained from
      clinical practice and from published sequences in the Stanford HIV-1 RT and
      Protease Sequence Database. The genotypic interpretation algorithms included:
      Stanford HIVdb program (HIVdb), the Visible Genetics/Bayer Diagnostics Guidelines
      6.0 (VGI) and a genotypic interpretation program (AntiRetroScan, ARS) developed
      at the University of Siena, Italy. Genotypic interpretations were normalized to a
      three-level output: susceptible, intermediate and resistant. Discordances were
      defined as differences between genotype and phenotype for the same virus isolate.
      Discordances for which an isolate was considered susceptible by one test but
      resistant by another test were considered major discordances. RESULTS: The
      frequency of major discordances between genotype and phenotype was 10.6, 13.7 and
      15.7% for ARS, VGI and HIVdb, respectively (P < 0.0001 for ARS versus HIVdb and
      for ARS versus VGI; P = 0.002 for VGI versus HIVdb). The correlation between
      genotype and phenotype was highest for non-nucleoside RT inhibitors and lowest
      for nucleoside RT inhibitors. Half of the major discordances involved stavudine,
      didanosine and zalcitabine. The concordance among the three genotypic algorithms
      was high, with weighted Kappa values ranging between 0.76 and 0.84 for the
      pairwise comparisons between each of the algorithms. CONCLUSIONS: Genotype
      interpretation algorithms correctly predict phenotype in 85-90% of cases, but the
      rate of concordance is not uniformly distributed among different drugs. These
      data provide insight into the potential additional benefit derived from
      phenotyping.

PMID- 14688054
TI  - In vitro susceptibility of Bacillus anthracis to various antibacterial agents and
      their time-kill activity.
AB  - OBJECTIVES: To investigate the in vitro acquisition of resistance to antibiotics
      by Bacillus anthracis. METHODS: The in vitro activities of 18 antibacterial
      agents against two strains of B. anthracis, the Sterne strain and the Russian
      anthrax vaccine strain ST-1, were tested by determining the MICs and by measuring
      the rates of antibiotic kill at 5x and 10x MIC. RESULTS: The fluoroquinolones
      ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin, the beta-lactams
      penicillin G and amoxicillin, the macrolide clarithromycin, the ketolide
      telithromycin, as well as clindamycin, rifampicin and quinupristin/dalfopristin
      had MICs in the range of 0.03-0.25 mg/L. Minocycline had an MIC of 0.03 mg/L, as
      did penicillin, against the ST-1 strain. Ciprofloxacin had an MIC of 0.03 mg/L
      against both strains. Erythromycin, vancomycin and the oxazolidinone linezolid
      were less active (MIC 0.5-2.5 mg/L). Ceftriaxone was the least active, having an
      MIC of 8.0 mg/L. Chloramphenicol was inactive (MIC > 256 mg/L).
      Quinupristin/dalfopristin, rifampicin and moxifloxacin showed the most rapid
      bacterial killing, achieving a complete eradication of detectable organisms (2
      log(10) reduction within 0.5-3 h and 4 log(10) reduction within 0.5-4 h for both
      strains at concentrations of 5x and 10x the MIC). The beta-lactams and vancomycin
      demonstrated a 2-4 log(10) reduction within 5-15 h. Ceftriaxone had a similar
      effect to penicillin and amoxicillin against the ST-1 strain, but a slower effect
      than these two beta-lactams against the Sterne strain. The macrolides,
      tetracyclines and linezolid demonstrated a lower kill rate, while chloramphenicol
      did not kill at all. CONCLUSIONS: These data expand on the spectrum of agents
      recommended for the treatment of anthrax (ciprofloxacin, penicillin G and
      tetracyclines) and add new options, such as other fluoroquinolones, amoxicillin,
      rifampicin and quinupristin/dalfopristin, as potential therapeutic agents.

PMID- 14688055
TI  - Broadly impaired NK cell function in non-obese diabetic mice is partially
      restored by NK cell activation in vivo and by IL-12/IL-18 in vitro.
AB  - NK cells represent a link between innate and adaptive immunity, and may play a
      role in regulating autoimmune disorders. We have characterized the NK cell
      population in non-obese diabetic (NOD) mice. The percentage and absolute numbers
      of NK cells were similar in NOD and control MHC-matched B6.g7 mice. However, the
      capacity of NOD NK cells to mediate natural cytotoxicity as well as FcR- and
      Ly49D-mediated killing was compromised in vitro, suggesting a defect affecting
      multiple activation pathways. The defect was neither linked to the NK gene
      complex nor to the MHC, as determined by comparison with mice congenic for these
      regions. Introducing the beta(2)-microglobulin mutation on the NOD background
      further impaired NK cell function, showing that the compromised cytotoxic
      capacity in these two strains arises from two independent mechanisms. In vivo
      rejection responses against tumor cells and against MHC class I-deficient spleen
      cells were decreased in naive NOD recipients, but restored in mice pre-activated
      with tilorone, a potent activator of NK cells. In addition, killing of some tumor
      targets was restored in vitro after activation of NK cells with IL-12 plus IL-18
      or with IFN-alpha/beta, but not with IL-2. Interestingly, natural killing of RMA
      S targets by NOD NK cells could not be restored in vitro, indicating that
      restoration of killing capacity was only partial. Our data suggest a severe, but
      partially restorable, killing defect in NOD NK cells, affecting activation
      through several pathways.

PMID- 14688056
TI  - Therapeutic potential of IFN-gamma-modified dendritic cells in acute and chronic
      experimental allergic encephalomyelitis.
AB  - Dendritic cells (DC) are antigen-presenting cells specialized to regulate immune
      responses. DC not only control immunity, but also maintain tolerance to self
      antigens-two complementary functions that would ensure the integrity of the
      organism in an environment full of pathogens. Here we report that splenic DC that
      had been exposed in vitro to IFN-gamma (IFN-gamma-DC) exhibit therapeutic
      potential on acute experimental allergic encephalomyelitis (EAE) in Lewis rats,
      and on chronic-relapsing EAE in B6 and SJL/J mice. During incipient EAE [day 5
      post-immunization (p.i.) in rats, day 7 p.i. in mice], IFN-gamma-DC were injected
      s.c. Severity of clinical signs of EAE was dramatically inhibited in animals
      injected with IFN-gamma-DC, showing normal magnetic resonance imaging (MRI) of
      the spinal cord and brain. In contrast, the EAE rats receiving PBS or naive DC
      had severe clinical signs with multiple and extensive MRI lesions in the spinal
      cord and brain. IFN-gamma-DC triggered an antigen-specific IFN-gamma production,
      and induced apoptosis of CD4(+) T cells possibly through DC expressing
      indoleamine 2,3-dioxygenase and/or an IFN-gamma-dependent pathway. As a result,
      infiltration of macrophages and CD4(+) T cells within the spinal cords was
      dramatically reduced in animals injected with IFN-gamma-DC as compared to animals
      injected with PBS or naive DC. This approach may represent a novel possibility of
      individualized immunotherapy using autologous, in vitro modified DC as a
      complement to conventional therapy in multiple sclerosis and other diseases with
      an autoimmune background.

PMID- 14688057
TI  - Differential regulation of NK cell proliferation by type I and type II IFN.
AB  - IFN, produced during viral infections by accessory (type I IFN) or NK cells (type
      II IFN), play a primary role in the regulation of immune and anti-viral NK cell
      effector functions. Because IFN have anti-proliferative effects on several cell
      types, including hematopoietic cells, we asked whether they modulate
      proliferation of human NK cells, and whether IFN-alpha and IFN-gamma mediate
      distinct effects on NK cells at different developmental stages. Analysis of
      proliferation at the single-cell level in human NK cells indicated that both IFN
      types inhibit IL-4-induced accumulation of immature CD56(-) IL-13(+) NK cells in
      freshly separated peripheral blood lymphocytes and in cells derived from them
      after short-term cultures. However, IFN-gamma inhibited specifically the IL-4
      dependent proliferation of these cells without affecting the IL-2-dependent one
      or that of the IL-13(-) cells, whereas IFN-alpha attenuated proliferation of NK
      cells at any developmental stage (both immature CD56(-)IL-13(+) and mature
      CD56(+)IL-13(-) IFN-gamma(+) NK cells) and contributed to their monokine-induced
      differentiation to IFN-gamma-producing cells. Adding to our previous report that
      IL-13 inhibits accumulation of mature IFN-gamma(+) NK cells, the present data
      unravel a mechanism by which peripheral immature IL-13(+) and mature IFN-gamma(+)
      NK cells can negatively regulate each other's accumulation.

PMID- 14688058
TI  - Human T lymphoblasts and activated dendritic cells in the allogeneic mixed
      leukocyte reaction are susceptible to NK cell-mediated anti-CD83-dependent
      cytotoxicity.
AB  - CD83 is a marker of dendritic cell (DC) differentiation/activation and its
      expression in the mouse thymus contributes to CD4(+) T lymphocyte development.
      Its extrathymic role remains unclear despite the functional effects observed with
      CD83 fusion proteins or CD83 antibody and recent reports of potential ligands. We
      investigated the previously observed and presumed functional blockade of the
      allogeneic mixed leukocyte reaction (MLR) with rabbit polyclonal anti-CD83
      (RA83). RA83 inhibition of T lymphocyte proliferation stimulated with allogeneic
      immature monocyte-derived DC (iMoDC) was confirmed. However, we found it was due
      to antibody-dependent cellular cytotoxicity (ADCC) mediated by NK cells in the
      responder T cell preparation. The likely targets of the ADCC were MoDC that had
      up-regulated CD83 during the MLR. Using a (51)Cr-release assay, we confirmed that
      CD83(+) MoDC, but not CD83(-) MoDC, are lysed by NK cells in the presence of
      RA83. However, prior fixation of the stimulator MoDC in the allogeneic MLR did
      not abrogate RA83 inhibition, indicating that cells from the responder T
      lymphocyte preparation, involved in the MLR proliferative response, also
      expressed CD83. We found, after 3-4 days of culture with allogeneic MoDC, a
      subset of CD3(+) cells had up-regulated CD83 and CD25. These were blasting T
      cells and, when isolated from the MLR, were found to be lysed by autologous NK
      cells in the presence of RA83. Thus, CD83 is expressed by responding T cells as
      well as by stimulating cells in the MLR and both are susceptible to anti-CD83
      mediated ADCC.

PMID- 14688059
TI  - Impeded Th1 CD4 memory T cell generation in chronic-persisting liver infection
      with Echinococcus multilocularis.
AB  - Memory T cells of the CD4 lineage coordinate immune responses against pathogens
      via the antigen-induced secretion of potent effector cytokines. The efficacy of
      these responses is thought to depend on both the overall number of pathogen
      specific memory T cells and the particular array of cytokines that these cells
      are programmed to secrete. It is unknown to what extent cellular immunity can be
      induced by Echinococcus multilocularis infection. To examine the immunological
      memory provided by the adaptive cellular immune system in control of the chronic
      persisting infection, peripheral lymphocytes of patients with alveolar
      echinococcosis (AE) were studied ex vivo. Stimulation of memory cells was
      performed with E. multilocularis vesicular fluid, purified protein derivative as
      recall antigen and phytohemagglutinin. Cytomegalovirus latency served as disease
      control. Frequencies of circulating CD4(+) T cells secreting IFN-gamma, IL-2,
      tumor necrosis factor-alpha, IL-4, IL-5 and IL-10 were determined by both
      cytokine flow cytometry and ELISPOT assays. Most strikingly, in chronic AE the
      frequencies of E. multilocularis antigen-specific cells committed to T(h)1
      cytokine production were low (mean 0.5% of CD4(+) T cells). However, an E.
      multilocularis-specific response of CD4(+) T cells at frequencies of >/=0.1% was
      detected in the majority of AE patients (68%). Low numbers of cells committed to
      T(h)1 cytokine secretion were invariably seen in patients with active and
      inactive disease. Interestingly, the number of specific CD4(+) memory T cells was
      not increased in cured AE patients after complete surgical removal of the
      metacestode. Hyporesponsiveness during the chronic helminth infection was E.
      multilocularis specific. Thus, our results demonstrate that antigen-specific
      memory function against E. multilocularis is markedly different from that against
      viral or bacterial pathogens. Whether the antigen-specific cellular
      hyporesponsiveness with impeded T(h)1 CD4(+) memory T cell generation is a cause
      or a result of the progressive metacestode activity remains to be determined.

PMID- 14688060
TI  - Paradoxical alteration of acute-phase protein levels in patients with chronic
      hepatitis C treated with IFN-alpha2b.
AB  - Previously we observed elevation of the serum concentration of two acute-phase
      protein (AFP) complement components (C9 and C1-inhibitor) in patients with
      chronic hepatitis C who responded (R) to IFN-alpha therapy, but not in non
      responders (NR). In the present study we investigated the effect of high-dose IFN
      alpha therapy on serum concentrations of two positive [orosomucoid (OROSO) and C
      reactive protein (CRP)] and two negative [transferrin (TF) and fetuin/alpha2HS
      glycoprotein (AHSG)] AFP in an outpatient setting. We investigated blood samples
      of 40 patients with chronic hepatitis C at the onset and at the end of a 3-month
      treatment with high-dose IFN-alpha2b (5 MIU/day for 6 weeks, followed by 5 MIU
      t.i.w.) and of 52 healthy individuals. Serum concentrations of OROSO, TF and AHSG
      were measured by radial immunodiffusion; CRP levels were determined by
      immunotubridimetry. Compared to controls, patients with chronic hepatitis C had
      significantly lower OROSO and CRP, and higher AHSG levels. By the end of
      treatment, OROSO concentration increased in R (P = 0.0054), but not in NR
      patients. In contrast, TF levels decreased in R (P = 0.0040), but did not change
      in NR patients. Similarly, in R patients, AHSG levels tended to decrease (P =
      0.0942) following IFN-alpha treatment. We conclude that the acute-phase reaction
      is suppressed in patients with chronic hepatitis C that may be potentially
      related to the responsiveness to IFN-alpha therapy.

PMID- 14688061
TI  - Polyriboinosinic polyribocytidylic acid [poly(I:C)]/TLR3 signaling allows class I
      processing of exogenous protein and induction of HIV-specific CD8+ cytotoxic T
      lymphocytes.
AB  - In the case of viral infection, various viral proteins and genetic components are
      disseminated in the body. The former viral proteins may be captured by immature
      dendritic cells (DC) and the latter genetic components may stimulate the antigen
      loading DC to maturate via specific Toll-like receptors (TLR), leading to the
      establishment of virus-specific cellular immunity; in particular, cytotoxic T
      lymphocytes (CTL) that control intracellular virions. Polyriboinosinic
      polyribocytidylic acid [poly(I:C)], which might reflect a natural genetic product
      from a variety of viruses during replication, has recently been identified as one
      of the critical stimuli for TLR3. Based on these observations, we speculated that
      stimulation of TLR3 with poly(I:C) might drive the direction of acquired/adaptive
      immunity to the cellular arm. Indeed, when BALB/c mice were immunized with
      purified recombinant HIV-1 envelope gp120 or influenza hemagglutinin (HA) protein
      together with poly(I:C), epitope-specific CD8(+) class I MHC molecule-restricted
      CTL were primed from naive CD8(+) T cells in vivo. In contrast, when the same
      proteins were immunized with lipopolysaccharide, a stimulant of TLR4, specific
      CTL were not primed at all. Moreover, we show here that immature DC could present
      processed antigen from captured purified protein in association with class I MHC
      molecules in the presence of poly(I:C), but not of LPS. These results indicate
      that we are able to manipulate the direction of acquired/adaptive effector immune
      responses using an appropriate stimuli and the findings presented in this paper
      will offer a new therapeutic strategy using poly(I:C) administration for priming
      antigen-specific CD8(+) CTL with purified viral protein in vivo.

PMID- 14688062
TI  - Importance of class II transactivator leucine-rich repeats for dominant-negative
      function and nucleo-cytoplasmic transport.
AB  - Class II transactivator (CIITA), the master regulator of MHC class II (MHC-II)
      gene transcription, shows a complex behavior in terms of self-association, nucleo
      cytoplasmic transport and MHC-II gene transactivation. Here, we analyzed the
      mechanisms of dominant-negative function and nucleo-cytoplasmic transport of
      CIITA with emphasis on the role of the C-terminal leucine-rich-repeat (LRR)
      region in these processes. First, we determined nucleo-cytoplasmic transport of
      endogenous CIITA and thus validated results obtained with epitope-tagged CIITA
      constructs. LRR mutations in potential protein-protein contact positions lead to
      either completely blocked or reduced nuclear import, but can also give rise to
      increased nuclear export. Surprisingly, N-terminally truncated CIITA mutants show
      dominant-negative inhibition of wild-type CIITA, whether they are located in the
      nucleus or in the cytoplasm. Integrity of the LRR is necessary for the dominant
      negative function of both types of mutants. LRR mutations are dominant over the
      effect of an exogenously added N-terminal nuclear localization signal (NLS)
      leading to cytoplasmic localization. Taken together, our results show that the
      LRR regulate the function of one or several NLS within CIITA, and control both
      nuclear import and export. Self-association is not affected in these mutants; we
      therefore suggest that interaction of the LRR with an unknown protein partner may
      be necessary for import and transactivation function of CIITA.

PMID- 14688063
TI  - Regulation of chronic colitis in athymic nu/nu (nude) mice.
AB  - The objective of this study was to assess the roles of NK cells, B cells and/or
      intraepithelial lymphocytes (IEL) in suppressing the development of colitis in
      nude mice reconstituted with CD4(+)CD45RB(high) T cells. BALB/c nude mice were
      lethally irradiated and reconstituted with bone marrow from different
      immunodeficient mice to generate athymic chimeras devoid of one or more
      lymphocyte populations. Transfer of CD4(+)C45RB(high) T cells into chimeric
      recipients devoid of B cells, T cells and IEL produced severe colitis within 6-8
      weeks, whereas transfer of these same T cells into B cell- and T cell-deficient
      or T cell-deficient chimeras produced little to no gut inflammation. In addition,
      we found that nude mice depleted of NK cells or RAG-1(-/-) mice reconstituted
      with IEL failed to develop colitis following transfer of CD45RB(high) T cells.
      Severe colitis could, however, be induced in nude mice by transfer of
      activated/T(h)1 CD4(+)CD45RB(low) T cells. Taken together, our data suggest that
      IEL, but not B cells or NK cells, play an important role in suppressing the
      development of chronic colitis in this model. In addition, our data demonstrate
      that suppression of disease may be due to polarization of naive CD4(+) cells
      toward a non-pathogenic and/or regulatory phenotype.

PMID- 14688064
TI  - Cell culture modeling of specialized tissue: identification of genes expressed
      specifically by follicle-associated epithelium of Peyer's patch by expression
      profiling of Caco-2/Raji co-cultures.
AB  - Peyer's patch follicle-associated epithelium (FAE) regulates intestinal antigen
      access to the immune system in part through the action of microfold (M) cells
      which mediate transcytosis of antigens and microorganisms. Studies on M cells
      have been limited by the difficulties in isolating purified cells, so we applied
      TOGA mRNA expression profiling to identify genes associated with the in vitro
      induction of M cell-like features in Caco-2 cells and tested them against normal
      Peyer's patch tissue for their expression in FAE. Among the genes identified by
      this method, laminin beta3, a matrix metalloproteinase and a tetraspan family
      member, showed enriched expression in FAE of mouse Peyer's patches. Moreover, the
      C. perfringens enterotoxin receptor (CPE-R) appeared to be expressed more
      strongly by UEA-1(+) M cells relative to neighboring FAE. Expression of the
      tetraspan TM4SF3 gene and CPE-R was also confirmed in human Peyer's patch FAE.
      Our results suggest that while the Caco-2 differentiation model is associated
      with some functional features of M cells, the genes induced may instead reflect
      the acquisition of a more general FAE phenotype, sharing only select features
      with the M cell subset.

PMID- 14688065
TI  - Monocyte cytotoxicity during acute kidney graft rejection in rats.
AB  - Surface antigens, mRNA expression patterns and intravascular accumulation
      suggested that monocytes might directly participate in acute renal allograft
      rejection in rats. A flow cytometry-based cytotoxicity assay was used in the
      present study to analyze the cytotoxic activity of monocytes from the renal and
      the whole extrapulmonary vasculature of kidney graft recipients (DA to LEW or LEW
      to LEW) and of untreated animals. The NK-sensitive lymphoma Yac-1 and the NO
      sensitive mastocytoma P815 were labeled with FITC and used as target cells.
      Cellular damage was demonstrated with propidium iodide (PI) or merocyanine 540
      (MC 540). On day 4 after allogeneic kidney transplantation the monocyte
      cytotoxicity towards Yac-1 increased 2-fold in comparison to control animals,
      whereas cytotoxicity towards P815 cells did not change considerably. PI and MC
      540 staining indicated pro-necrotic as well as pro-apoptotic cytotoxic
      mechanisms. Furthermore, monocytes obviously damaged targets by cytotoxic
      mechanisms differing from NK cells. In conclusion, monocyte cytotoxicity might be
      an important effector mechanism in acute renal allograft rejection.

PMID- 14688066
TI  - Functionally active CD8alphabeta+ TCRgammadelta intestinal intraepithelial
      lymphocytes in athymic nu/nu mice.
AB  - Murine intestinal intraepithelial lymphocytes (IEL) encompass a high proportion
      of TCRgammadelta cells. A vast majority of these TCRgammadelta IEL express
      CD8alpha, but not CD8beta (CD8alphaalpha homodimer), and are considered to
      develop in intestinal epithelial layers independently of a functional thymus.
      Here we show that TCRgammadelta cells expressing both CD8alpha and CD8beta
      (CD8alphabeta heterodimer) appear in athymic nu/nu mice, although their
      appearance is random. The IEL comprising CD8alphabeta(+) TCRgammadelta cells
      expressed pronounced cytolytic and IFN-gamma-producing activities after
      TCRgammadelta ligation, which were markedly stronger than activities of IEL
      lacking CD8alphabeta(+) TCRgammadelta cells. Purified CD8alphabeta(+)
      TCRgammadelta cells expressed strong cytolytic activities and produced large
      quantities of IFN-gamma after TCR engagement. CD8alphabeta(+) TCRgammadelta cells
      were also identified among IEL from euthymic C57BL/6 mice, although their
      abundance varied among individual animals. However, cytolytic and IFN-gamma
      producing activities in euthymic C57BL/6 mice were markedly lower than those in
      athymic nu/nu mice. Our findings suggest that CD8alphabeta(+) TCRgammadelta cells
      can develop in the intestine independently of a functional thymus/thymic
      epithelial cells and that they perform biological functions in situ.

PMID- 14688067
TI  - Mouse CD20 expression and function.
AB  - CD20 plays a role in human B cell proliferation and is an effective target for
      immunotherapy. In this study, mouse CD20 expression and biochemistry were
      assessed for the first time using a new panel of CD20-specific mAb, with CD20
      function assessed using CD20-deficient (CD20(-/-)) mice. CD20 expression was B
      cell restricted and was initiated during late pre-B cell development. The
      frequency and density of CD20 expression increased during B cell maturation in
      the bone marrow, with a subpopulation of transitional IgM(hi) B cells expressing
      higher CD20 levels than the majority of mature recirculating B cells.
      Transitional T1 B cells in the spleen also expressed high CD20 levels, providing
      a useful new marker for this B cell subset. In CD20(-/-) mice, immature and
      mature B cell IgM expression was approximately 20-30% lower relative to B cells
      from wild-type littermates. In addition, CD19-induced intracellular calcium
      responses were significantly reduced in CD20(-/-) B cells, with a less dramatic
      effect on IgM-induced responses. These results reveal a role for CD20 in
      transmembrane Ca(2+) movement in mouse primary B cells that complements previous
      results obtained using human CD20 cDNA-transfected cell lines. Otherwise, B cell
      development, tissue localization, signal transduction, proliferation, T cell
      dependent antibody responses and affinity maturation were normal in CD20(-/-)
      mice. Thus, mouse and human CD20 share similar patterns of expression and
      function. These studies thereby provide an animal model for studying CD20
      function in vivo and the molecular mechanisms that influence anti-CD20
      immunotherapy.

PMID- 14688068
TI  - T cells accumulating in the inflamed joints of a spontaneous murine model of
      rheumatoid arthritis become restricted to common clonotypes during disease
      progression.
AB  - Although a number of studies have revealed that T cells expand clonally in the
      joints of patients suffering from rheumatoid arthritis (RA), the kinetics of T
      cell clonality in multiple joints of an individual throughout progression of the
      disease is not known. By employing a TCR beta chain gene-specific RT-PCR and
      subsequent single-strand conformation polymorphism, which enables us to monitor T
      cell clonality, we analyzed transgenic mice (Tg) carrying the human T cell
      leukemia virus type I env-pX region. These mice spontaneously develop destructive
      progressive arthritis similar to RA as they age. In the early stage, the majority
      of accumulating T cell clones differed in each of four affected feet analyzed.
      However, in the advanced stage, many of the clones were common to all four feet.
      The total number of distinct clones gradually decreased as the disease
      progressed. When splenocytes from arthritic elder Tg were adoptively transferred
      into either nude mice or young Tg, the clones common to all four feet of the
      donor were detected again in four feet of the recipients. These findings suggest
      that, as arthritis progresses, the T cell clones accumulating in the arthritic
      joints are gradually restricted to certain common clonotypes, some of which are
      arthrotropic.

PMID- 14688069
TI  - Chicken BAFF--a highly conserved cytokine that mediates B cell survival.
AB  - Members of the tumor necrosis factor (TNF) family play key roles in the
      regulation of inflammation, immune responses and tissue homeostasis. Here we
      describe the identification of the chicken homologue of mammalian B cell
      activating factor of the TNF family (BAFF/BLyS). By searching a chicken EST
      database we identified two overlapping cDNA clones that code for the entire open
      reading frame of chicken BAFF (chBAFF), which contains a predicted transmembrane
      domain and a putative furin protease cleavage site like its mammalian
      counterparts. The amino acid identity between soluble chicken and human BAFF is
      76%, considerably higher than for most other known cytokines. The chBAFF gene is
      most strongly expressed in the bursa of Fabricius. Soluble recombinant chBAFF
      produced by human 293T cells interacted with the mammalian cell-surface receptors
      TACI, BCMA and BAFF-R. It bound to chicken B cells, but not to other lymphocytes,
      and it promoted the survival of splenic chicken B cells in culture. Furthermore,
      bacterially expressed chBAFF induced the selective expansion of B cells in the
      spleen and cecal tonsils when administered to young chicks. Our results suggest
      that like its mammalian counterpart, chBAFF plays an important role in survival
      and/or proliferation of chicken B cells.

PMID- 14688070
TI  - The exploitation of distinct recognition receptors in dendritic cells determines
      the full range of host immune relationships with Candida albicans.
AB  - Dendritic cells (DC) sense saprophytic yeast and pathogenic, filamentous forms of
      Candida albicans in a specific way, resulting in disparate patterns of DC and
      T(h) cell activation. Using human and murine DC, such disparate patterns could be
      traced to the exploitation of distinct recognition receptors. Although usage of
      mannose receptors led to protective type 1 responses in mice, entry through
      Fcgamma receptors was responsible for suppression of mannose receptor-dependent
      reactivity, onset of type 2 responses and associated pathology. As the usage of
      distinct receptors selectively occurred with yeast or hyphal forms of the fungus,
      these findings suggest that the responsibility for pathogenicity of C. albicans
      is shared by the organism and DC, with implications for fungal virulence,
      immunity and vaccine development.

PMID- 14688071
TI  - Molecular genetic analyses of human NKG2C (KLRC2) gene deletion.
AB  - Human NKG2A, NKG2C and NKG2E genes are located on 12p13 in the NK gene complex.
      We recently identified deletion of NKG2C in a Japanese population. This study was
      performed to identify the breakpoint, and to examine the association of NKG2C
      deletion with susceptibility to rheumatoid arthritis and systemic lupus
      erythematosus. The location of the breakpoint was determined to be 1.5-1.8 kb
      telomeric from the 3' end of NKG2A by comparing sequences of the intergenic
      segments upstream and downstream of the NKG2C gene in the common haplotype with
      the intergenic sequence between NKG2A and NKG2E in the deletion haplotype. Based
      on this information, a genotyping system was developed. The frequency of NKG2C
      deletion haplotype was 20.2% in Japanese and 20.0% in Dutch populations. The
      frequency of homozygous deletion was 4.1% in Japanese and 3.8% in Dutch. Evidence
      for an association with rheumatic diseases was not detected. These results
      indicated that NKG2C deletion is commonly present in Japanese and Dutch,
      suggesting that NKG2C is not essential for survival and reproduction, and is not
      associated with rheumatic diseases.

PMID- 14688072
TI  - Identification and characterization of a novel spliced variant that encodes human
      soluble tumor necrosis factor receptor 2.
AB  - Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine involved in a broad
      spectrum of inflammatory and immune responses including proliferation,
      differentiation and cell death induction in several cell types. The biological
      effects of TNF-alpha are mediated via the cell-surface TNF receptors TNFR1 and
      TNFR2. Soluble forms of these two receptors, which contain the extracellular
      ectodomains, are proteolytically cleaved from the membrane. High levels of
      soluble (s) TNFR2 in serum have been documented in multiple inflammatory
      pathologies. We describe here a new differential spliced isoform of human TNFR2
      missing exons 7 and 8, DS-TNFR2(Delta7,8). This novel isoform lacks the
      transmembrane and cytoplasmic domains. Expression studies with DS-TNFR2(Delta7,8)
      cDNA transiently transfected COS cells showed that it encodes a sTNFR2 receptor
      of approximately 42 kDa. Soluble DS-TNFR2(Delta7,8) blocked TNF-alpha-induced
      apoptosis, which suggests that it regulates TNF-alpha function by antagonizing
      its biological activity. An ELISA was developed that quantifies sTNFR2 generated
      by alternative splicing. Our data show that sTNFR2 generated by alternative
      splicing can be found in sera of healthy individuals, at increased levels in
      patients with sepsis and at high concentrations in rheumatoid arthritis patients.

PMID- 14688073
TI  - Evidence of GATA-3-dependent Th2 commitment during the in vivo immune response.
AB  - The transcription factor GATA-3 has been shown to play an important role for the
      in vitro induction of T(h)2 cells. To clarify how the in vivo immune response is
      governed under GATA-3 function, we generated double-transgenic mice by crossing
      GATA-3 transgenic mice with ovalbumin (OVA)-specific TCR transgenic mice. After
      immunization with OVA, the double-transgenic mice showed increased expression of
      GATA-3 in antigen-reactive fresh CD4(+) T cells, and higher production of IL-5
      and IL-13 in cultured spleen cells in the presence of cognate antigen without any
      polarizing conditions for T(h)2 cells. Moreover, the immunized double-transgenic
      mice showed a higher increase of in vivo secretion of IL-5 and IL-13 in
      bronchoalveolar lavage fluid after OVA aerosol challenging. The serum levels of
      OVA-specific IgG1, IgE and IgA antibodies were much higher in the immunized
      double-transgenic mice than TCR transgenic mice. These findings provide direct
      evidence that antigen-stimulated CD4(+) T cells in the immunized mice have
      already been committed into T(h)2 cells producing IL-5 and IL-13 selectively
      through enhanced GATA-3 expression in vivo, thereby inducing higher production of
      antigen-specific antibody for three isotypes other than IgM.

PMID- 14688075
TI  - Further characterization of immunomodulation by a monoclonal antibody against
      Streptococcus mutans antigen P1.
AB  - We demonstrated previously that mucosal immunization of mice with Streptococcus
      mutans coated with the monoclonal antibody (MAb) 6-11A directed against the major
      surface adhesin protein P1 results in changes in the amount, isotype
      distribution, and specificity of serum antibodies compared with animals immunized
      with bacteria only. We now show that the specificity of the mucosal secretory IgA
      response was also influenced by this MAb. Changes in antibody specificity were
      associated with changes in biological activity. Serum samples which differed in
      antibody reactivity with P1 polypeptides generated by partial digestion with N
      chlorosuccinimide but not in isotype distribution or overall reactivity with S.
      mutans or intact P1 demonstrated a statistically significant difference in the
      ability to inhibit bacterial adherence to salivary-agglutinin-coated
      hydroxyapatite beads. Serum IgG antibodies against P1 from mice immunized with
      either S. mutans alone or S. mutans coated with 6-11A were shown to recognize
      antigenic determinants dependent on the presence of the central proline-rich
      repeat domain, a segment necessary for the structural integrity of the molecule.
      However, no statistically significant differences were observed in antibody
      reactivity with a panel of six partial P1 polypeptides encoded by overlapping
      spaP subclones, suggesting that the targets of biologically relevant antibodies
      involve complex epitopes not reconstituted by the recombinant products tested.
      Lastly, we show that binding of MAb 6-11A to P1 on the surface of S. mutans
      alters P1's susceptibility to proteolytic digestion. Hence, changes in antigen
      processing and presentation may contribute to the immunomodulatory effects of
      this MAb.

PMID- 14688076
TI  - Salmonella enterica serovar Paratyphi C carries an inactive shufflon.
AB  - Salmonella enterica serovar Typhi uses type IVB pili to facilitate bacterial self
      association, but only when the PilV proteins (potential minor pilus proteins) are
      not synthesized. This pilus-mediated event may be important in typhoid fever
      pathogenesis. We initially show that S. enterica serovar Paratyphi C strains
      harbor a pil operon very similar to that of serovar Typhi. An important
      difference, however, is located in the shufflon which concludes the pil operon.
      In serovar Typhi, the Rci recombinase acts upon two 19-bp inverted repeats to
      invert the terminal region of the pilV gene, thereby disrupting PilV synthesis
      and permitting bacterial self-association. In serovar Paratyphi C, however, the
      shufflon is essentially inactive because each of the Rci 19-bp substrates has
      acquired a single base pair insertion. A PilV protein is thus synthesized
      whenever the pil operon is active, and bacterial self-association therefore does
      not occur in serovar Paratyphi C. The data thus suggest that serovar Typhi
      bacterial self-association using type IVB pili may be important in the
      pathogenesis of epidemic enteric fever.

PMID- 14688074
TI  - Regulation of granulomatous inflammation in experimental models of
      schistosomiasis.

PMID- 14688077
TI  - Role of siderophore biosynthesis in virulence of Staphylococcus aureus:
      identification and characterization of genes involved in production of a
      siderophore.
AB  - Molecular determinants underlying the production of siderophores in the human and
      animal pathogen Staphylococcus aureus and the contribution of siderophore
      production to the virulence of this bacterium have, until now, remained
      undefined. Here, we show that S. aureus strains RN6390 and Newman produce
      siderophore when the cells are starved for iron. We further identified and
      characterized a nine-gene, iron-regulated operon, designated sbn and situated
      between sirABC and galE on the S. aureus chromosome, that is involved in the
      production of a siderophore. Mutation of the sbnE gene, in both RN6390 and
      Newman, eliminates the ability of these strains to produce a siderophore under
      iron-limited growth conditions, while introduction of multicopy sbnE into sbnE
      mutants complemented the inability of the mutants to produce the siderophore.
      sbnE mutants, in both the RN6390 and Newman backgrounds, displayed a drastic
      growth deficiency, compared to the wild type, in iron-restricted growth medium,
      whereas no such deficiency was observed during growth in iron-replete medium.
      Complemented mutants showed a restored ability to grow under iron restriction. We
      further showed that an sbnE mutant was compromised in a murine kidney abscess
      model of S. aureus infection, illustrating the importance of siderophore
      production to the pathogenicity of S. aureus. sbn genes were present in all S.
      aureus strains tested (and all S. aureus genome sequences) but were undetectable
      in any of the 13 coagulase-negative staphylococci tested, including
      Staphylococcus epidermidis.

PMID- 14688078
TI  - Long-term effect of heat shock protein 60 from Actinobacillus
      actinomycetemcomitans on epithelial cell viability and mitogen-activated protein
      kinases.
AB  - Our previous studies showed that bacterial heat shock protein 60 (hsp60) induces
      cultured epithelial cell proliferation within 24 h. Here we investigated the long
      term effects of heat shock protein 60 isolated from Actinobacillus
      actinomycetemcomitans on skin keratinocyte (HaCaT cell line) viability and the
      cell signaling involved. Prolonged incubation in the presence of hsp60 increased
      the rate of epithelial cell death. The number of viable cells in hsp60-treated
      culture was 37% higher than the number in the control at 24 h but 27% lower at
      144 h. A kinetics study of the effect of hsp60 on the phosphorylation of mitogen
      activated protein kinases (MAPKs) involving Western blotting with phospho
      specific antibodies showed that in addition to a transient early increase in p38
      levels, a second peak appeared in keratinocytes 24 h after the addition of hsp60.
      In contrast, prolonged incubation with hsp60 caused a decrease in the level of
      phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) compared with
      that in the controls, possibly as a result of protein phosphatase activity. We
      found that hsp60 increased the levels of several phosphatases, including MAP-2,
      which strongly dephosphorylates ERK1/2. Moreover, hsp60 increased the level of
      tumor necrosis factor alpha (TNF-alpha) in culture medium in a dose-dependent
      manner. TNF-alpha added to culture showed a cytotoxic effect on epithelial cells,
      particularly with longer incubation periods. TNF-alpha also induced the
      phosphorylation of p38. Finally, our results show that bacterial hsp60 inhibited
      stress-induced synthesis of cellular hsp60. Therefore, several cell behavior
      changes caused by long-term exposure to bacterial hsp60 may lead to impaired
      epithelial cell viability.

PMID- 14688079
TI  - Immunotherapy of Trypanosoma cruzi infection with DNA vaccines in mice.
AB  - The mechanisms involved in the pathology of chronic chagasic cardiomyopathy are
      still debated, and the controversy has interfered with the development of new
      treatments and vaccines. Because of the potential of DNA vaccines for
      immunotherapy of chronic and infectious diseases, we tested if DNA vaccines could
      control an ongoing Trypanosoma cruzi infection. BALB/c mice were infected with a
      lethal dose (5 x 10(4) parasites) as a model of acute infection, and then they
      were treated with two injections of 100 microg of plasmid DNA 1 week apart,
      beginning on day 5 postinfection. Control mice had high levels of parasitemia and
      mortality and severe cardiac inflammation, while mice treated with plasmid DNA
      encoding trypomastigote surface antigen 1 or Tc24 had reduced parasitemia and
      mild cardiac inflammation and >70% survived the infection. The efficacy of the
      immunotherapy also was significant when it was delayed until days 10 and 15 after
      infection. Parasitological analysis of cardiac tissue of surviving mice indicated
      that most mice still contained detectable parasite kinetoplast DNA but fewer mice
      contained live parasites, suggesting that there was efficient but not complete
      parasite elimination. DNA vaccine immunotherapy was also evaluated in CD1 mice
      infected with a low dose (5 x 10(2) parasites) as a model of chronic infection.
      Immunotherapy was initiated on day 70 postinfection and resulted in improved
      survival and reduced cardiac tissue inflammation. These results suggest that DNA
      vaccines have strong potential for the immunotherapy of T. cruzi infection and
      may provide new alternatives for the control of Chagas' disease.

PMID- 14688080
TI  - A gene, uge, is essential for Klebsiella pneumoniae virulence.
AB  - Klebsiella pneumoniae strains typically express both smooth lipopolysaccharide
      (LPS) with O antigen molecules and capsule polysaccharide (K antigen) on the
      surface. A single mutation in a gene that codes for a UDP galacturonate 4
      epimerase (uge) renders a strain with the O-:K- phenotype (lack of capsule and
      LPS without O antigen molecules and outer core oligosaccharide). The uge gene was
      present in all the K. pneumoniae strains tested. The K. pneumoniae uge mutants
      were unable to produce experimental urinary tract infections in rats and were
      completely avirulent in two different animal models (septicemia and pneumonia).
      Reintroduction of the single uge wild-type gene in the corresponding mutants
      completely restored the wild-type phenotype (presence of capsule and smooth LPS)
      independently of the O or K serotype of the wild type. Furthermore, complemented
      uge mutants recovered the ability to produce experimental urinary tract
      infections in rats and virulence in the septicemia and pneumonia animal models.

PMID- 14688081
TI  - Mycobacterium bovis BCG vaccination as prophylaxis against Mycobacterium ulcerans
      osteomyelitis in Buruli ulcer disease.
AB  - Mycobacterium ulcerans disease, or Buruli ulcer (BU), causes significant
      morbidity in West Africa. Clinically, the disease presents in the skin as either
      nonulcerative or ulcerative forms and often invades bones either subjacent to the
      skin lesion (contiguous osteomyelitis) or remote from the skin lesion (metastatic
      osteomyelitis). Osteomyelitis represents a severe form of the disease that often
      requires numerous surgical interventions, even amputations. Surgery is accepted
      as the present definitive treatment for BU. In the absence of an effective drug
      treatment, the need for the development of preventive and control strategies
      becomes paramount. No specific vaccine, however, is presently available for BU.
      Of 372 consecutive patients in Benin presenting with BU (confirmed by
      microbiological and histopathological analyses) whose Mycobacterium bovis BCG
      scar statuses were known, 196 children (<15 years old) and 108 adults had
      neonatal BCG vaccination scars. Of 196 children with BCG scars, 17 (8.7%) had
      osteomyelitis, while 7 of 28 children without BCG scars (25.0%) had
      osteomyelitis. Of 108 adults with BCG scars, 17 (15.7%) had osteomyelitis, while
      14 of 40 adults without BCG scars (35.0%) had osteomyelitis. Our results show
      that effective BCG vaccination at birth provides significant protection against
      the development of M. ulcerans osteomyelitis in children and adults. Therefore,
      health authorities should give attention to the enhancement of neonatal BCG
      vaccination coverage in all countries of Africa where BU is endemic. Protection
      against severe forms of BU and childhood tuberculosis would likewise be improved
      by this intervention.

PMID- 14688082
TI  - Development of an intranasal vaccine to prevent urinary tract infection by
      Proteus mirabilis.
AB  - Proteus mirabilis commonly infects the complicated urinary tract and is
      associated with urolithiasis. Stone formation is caused by bacterial urease,
      which hydrolyzes urea to ammonia, causing local pH to rise, and leads to the
      subsequent precipitation of magnesium ammonium phosphate (struvite) and calcium
      phosphate (apatite) crystals. To prevent these infections, we vaccinated CBA mice
      with formalin-killed bacteria or purified mannose-resistant, Proteus-like (MR/P)
      fimbriae, a surface antigen expressed by P. mirabilis during experimental urinary
      tract infection, via four routes of immunization: subcutaneous, intranasal,
      transurethral, and oral. We assessed the efficacy of vaccination using the CBA
      mouse model of ascending urinary tract infection. Subcutaneous or intranasal
      immunization with formalin-killed bacteria and intranasal or transurethral
      immunization with purified MR/P fimbriae significantly protected CBA mice from
      ascending urinary tract infection by P. mirabilis (P < 0.05). To investigate the
      potential of MrpH, the MR/P fimbrial tip adhesin, as a vaccine, the mature MrpH
      peptide (residues 23 to 275, excluding the signal peptide), and the N-terminal
      receptor-binding domain of MrpH (residues 23 to 157) were overexpressed as C
      terminal fusions to maltose-binding protein (MBP) and purified on amylose resins.
      Intranasal immunization of CBA mice with MBP-MrpH (residues 23 to 157) conferred
      effective protection against urinary tract infection by P. mirabilis (P < 0.002).

PMID- 14688083
TI  - Ability of pneumococcal serotypes and clones to cause acute otitis media:
      implications for the prevention of otitis media by conjugate vaccines.
AB  - The relative abilities of pneumococcal serotypes and strains (clones) to cause
      acute otitis media (AOM) were investigated by comparing the serotypes and
      genotypes of pneumococci recovered from cases of AOM (n = 149) in children <2
      years of age with those from nasopharyngeal carriage (n = 288) in age-matched
      controls from the same region. The odds ratio (OR) for association of pooled
      vaccine serotypes with AOM was found to be slightly elevated over unity, although
      this was not significantly different from that of pooled nonvaccine or vaccine
      related serotypes. Comparing individual serotypes, 19F and 23F had 2- to 2.5-fold
      higher ORs, although these were not markedly different from the ORs of nonvaccine
      serotypes. None of the major clones had an OR that was significantly greater than
      the average, and the differences in ORs among serotypes and clones were much less
      than those for invasive disease, suggesting little variation in their ability to
      cause AOM. We conclude that serotype replacement may reduce the long-term
      efficacy of these vaccines against AOM.

PMID- 14688084
TI  - Tissue inhibitor of metalloproteinase 1 activates normal human granulocytes,
      protects them from apoptosis, and blocks their transmigration during
      inflammation.
AB  - Urinary levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) higher than
      those of matrix metalloproteinase 9 (MMP-9) during acute pyelonephritis have
      previously been associated with a higher degree of acute inflammation and of
      postinfective renal scarring. The aim of the present study was to evaluate
      possible mechanisms by which TIMP-1 could affect the scarring process already
      during the acute phase of inflammation. The growth of Escherichia coli,
      bactericidal activity of fresh human blood, and respiratory burst, spontaneous
      apoptosis, and trans-basement membrane migration of normal human granulocytes
      were studied in vitro in the presence of different concentrations of recombinant
      human TIMP-1. To imitate the "normal" environment during inflammation in the
      kidney, granulocytes were also incubated with a conditioned medium from E. coli
      stimulated renal epithelial cells. In order to compare our data with the in vivo
      situation, blood and urinary leukocyte levels were analyzed for 40 children with
      acute pyelonephritis, together with urinary MMP-9 and TIMP-1 levels. TIMP-1 at a
      concentration of 500 ng/ml increased the bactericidal activity of blood,
      increased the respiratory burst of granulocytes, decreased phosphatidylserine
      exposure and caspase 3 activity, which are features of spontaneous apoptosis, and
      inhibited granulocyte transmigration. Moreover, in the patients with
      pyelonephritis, MMP-9/TIMP-1 ratios in urine correlated with the degree of
      leukocyte transmigration. Thus, our data suggest that TIMP-1 specifically blocks
      the transmigration of granulocytes into urine. Entrapped and activated
      granulocytes, protected from apoptosis, might excessively destroy renal
      parenchyma and thus contribute to the pathogenesis of renal scarring following
      acute pyelonephritis.

PMID- 14688085
TI  - Selective induction of tumor necrosis receptor factor 6/decoy receptor 3 release
      by bacterial antigens in human monocytes and myeloid dendritic cells.
AB  - Tumor necrosis factor (TNF) receptor 6/decoy receptor 3 (TR6/DcR3) is an
      antiapoptosis soluble receptor of the TNF family produced by tumor cells. In this
      study, TR6 expression in human immune cells was investigated. TR6 mRNA and
      protein were detectable in selected antigen-presenting cells. Monocytes and
      myeloid-derived dendritic cells (MDC) released the protein exclusively following
      stimulation of Toll-like receptor 2 (TLR2) and TLR4 by gram-positive and gram
      negative bacterial antigens. Plasmacytoid dendritic cells, activated by bacterial
      antigens via TLR9 or by viral infection, did not produce the protein. Similarly,
      activated T cells did not release TR6. The release of TR6 by MDC was dependent on
      the activation of p42/p44 mitogen-activated protein kinases, Src-like protein
      tyrosine kinases, and phosphatidylinositol 3-kinase, signaling pathways important
      for MDC maturation and survival. In agreement with the in vitro data, TR6 levels
      in serum were significantly elevated in patients with bacterial infections.
      Overall, these data suggest a novel role for TR6 in immune responses to bacteria.

PMID- 14688086
TI  - Role of the C-terminal lysine residues of streptococcal surface enolase in Glu-
      and Lys-plasminogen-binding activities of group A streptococci.
AB  - Streptococcal surface enolase (SEN) is a major plasminogen-binding protein of
      group A streptococci. Our earlier biochemical studies have suggested that the
      region responsible for this property is likely located at the C-terminal end of
      the SEN molecule. In the present study, the gene encoding SEN was cloned from
      group A streptococci M6 isolate D471. A series of mutations in the sen gene
      corresponding to the C-terminal region (428KSFYNLKK435) of the SEN molecule were
      created by either deleting one or more terminal lysine residues or replacing them
      with leucine. All purified recombinant SEN proteins with altered C-terminal ends
      were found to be enzymatically active and were analyzed for their Glu- and Lys
      plasminogen-binding activities. Wild-type SEN bound to Lys-plasminogen with
      almost three times more affinity than to Glu-plasminogen. However, the
      recombinant mutant SEN proteins with a deletion of Lys434-435 or with K435L and
      K434-435L replacements showed a significant decrease in Glu- and Lys-plasminogen
      binding activities. Accordingly, a streptococcal mutant expressing SEN-K434-435L
      showed a significant decrease in Glu- and Lys-plasminogen-binding activities.
      Biochemical and functional analyses of the isogenic mutant strain revealed a
      significant decrease in its abilities to cleave a chromogenic tripeptide
      substrate, acquire plasminogen from human plasma, and penetrate the extracellular
      matrix. Together, these data indicate that the last two C-terminal lysine
      residues of surface-exposed SEN contribute significantly to the plasminogen
      binding activity of intact group A streptococci and hence to their ability to
      exploit host properties to their own advantage in tissue invasion.

PMID- 14688087
TI  - Sialylation of lipooligosaccharides promotes biofilm formation by nontypeable
      Haemophilus influenzae.
AB  - Nontypeable Haemophilus influenzae (NTHi) is a major cause of opportunistic
      respiratory tract infections, including otitis media and bronchitis. The
      persistence of NTHi in vivo is thought to involve bacterial persistence in a
      biofilm community. Therefore, there is a need for further definition of bacterial
      factors contributing to biofilm formation by NTHi. Like other bacteria inhabiting
      host mucosal surfaces, NTHi has on its surface a diverse array of
      lipooligosaccharides (LOS) that influence host-bacterial interactions. In this
      study, we show that LOS containing sialic (N-acetyl-neuraminic) acid promotes
      biofilm formation by NTHi in vitro and bacterial persistence within the middle
      ear or lung in vivo. LOS from NTHi in biofilms was sialylated, as determined by
      comparison of electrophoretic mobilities and immunochemical reactivities before
      and after neuraminidase treatment. Biofilm formation was significantly reduced in
      media lacking sialic acid, and a siaB (CMP-sialic acid synthetase) mutant was
      deficient in biofilm formation in three different in vitro model systems. The
      persistence of an asialylated siaB mutant was attenuated in a gerbil middle ear
      infection model system, as well as in a rat pulmonary challenge model system.
      These data show that sialylated LOS glycoforms promote biofilm formation by NTHi
      and persistence in vivo.

PMID- 14688088
TI  - Effects of PspA and antibodies to PspA on activation and deposition of complement
      on the pneumococcal surface.
AB  - Streptococcus pneumoniae infection is a frequent cause of pneumonia, otitis
      media, meningitis, and septicemia. Pneumococcal surface protein A (PspA) is an
      important virulence factor on the pathogen surface, and it is known to interfere
      with complement activation. In this study, flow cytometry was used to study the
      effects of PspA and antibodies to PspA on the deposition of complement C3 on the
      surface of a capsular type 3 strain, WU2, and its PspA- mutant, JY1119. Using
      naive mouse serum as a complement source, measurable deposition of C3 was
      observed within 4 min on PspA- pneumococci, and the amount of surface-bound C3
      accumulated rapidly as the amount of serum was increased. In contrast, very
      little C3 was deposited on the PspA+ strain. In nonimmune mouse serum, the
      classical pathway was the dominant activation pathway triggered by PspA-
      pneumococci. Accordingly, EGTA blocked almost all of the complement activation.
      Moreover, a significant amount of C3 was still deposited on the PspA- strain when
      serum from factor B-deficient mice was used. This deposition was not observed on
      the PspA+ pneumococci, indicating that PspA may inhibit complement deposition via
      the classical pathway. Furthermore, under the conditions we tested, PspA also
      inhibited C3 deposition when the classical pathway was initiated by antibodies to
      capsular polysaccharide. Antibodies to PspA could overcome the anticomplementary
      effect of PspA, allowing for increased complement activation and C3 deposition
      onto PspA+ bacteria.

PMID- 14688089
TI  - Analysis of Mycobacterium species for the presence of a macrolide toxin,
      mycolactone.
AB  - Mycobacterium ulcerans is an environmental organism which is responsible for the
      disease Buruli ulcer, a necrotizing skin disease emerging in west Africa. M.
      ulcerans produces the polyketide-derived macrolide mycolactone, which is required
      for the immunosuppression and tissue damage which characterizes Buruli ulcer. We
      have extracted lipids from the cell envelope and culture filtrate from 52
      isolates of Mycobacterium species, analyzed them with thin-layer chromatography,
      and tested them in a murine fibroblast cell line (L929) cytotoxicity assay to
      investigate whether these mycobacterial species produce mycolactone. For these
      studies chloroform-methanol (2:1, vol/vol) extracts were prepared from
      representative fast- and slow-growing mycobacterial species. Isolates tested
      included 16 uncharacterized, slow-growing, environmental mycobacterial species
      isolated from areas in which M. ulcerans infection is endemic. Although several
      strains of mycobacteria studied produced cytopathic lipids, none of these
      produced a phenotype on cultured cells consistent with that produced by
      mycolactone. Two mycobacterial species, M. scrofulaceum and M. kansasii, and
      eight of the environmental mycobacterial isolates contained cell-associated
      lipids cytopathic to fibroblasts at concentrations of 33 to 1,000 microg/ml. In
      contrast, mycolactone produces cytotoxicity at less than 2 ng/ml. Analysis of 16S
      rRNA sequences from the eight environmental isolates suggests that these are
      novel mycobacterial species. Results from these studies suggest that, although
      production of cytopathic lipids is relatively common among mycobacterial species,
      the production of mycolactone as a cell-associated or secreted molecule appears
      so far to be restricted to M. ulcerans.

PMID- 14688090
TI  - Cross-sectional analysis of clinical and environmental isolates of Pseudomonas
      aeruginosa: biofilm formation, virulence, and genome diversity.
AB  - Chronic lung infections with Pseudomonas aeruginosa biofilms are associated with
      refractory and fatal pneumonia in cystic fibrosis (CF). In this study, a group of
      genomically diverse P. aeruginosa isolates were compared with the reference
      strain PAO1 to assess the roles of motility, twitching, growth rate, and
      overproduction of a capsular polysaccharide (alginate) in biofilm formation. In
      an in vitro biofilm assay system, P. aeruginosa displayed strain-specific biofilm
      formation that was not solely dependent on these parameters. Compared with non-CF
      isolates, CF isolates expressed two opposing growth modes: reduced planktonic
      growth versus efficient biofilm formation. Planktonic cells of CF isolates showed
      elevated sensitivity to hydrogen peroxide, a reactive oxygen intermediate, and
      decreased lung colonization in an aerosol infection mouse model. Despite having
      identical genomic profiles, CF sequential isolates produced different amounts of
      biofilm. While P. aeruginosa isolates exhibited genomic diversity, the genome
      size of these isolates was estimated to be 0.4 to 19% (27 to 1,184 kb) larger
      than that of PAO1. To identify these extra genetic materials, random
      amplification of polymorphic DNA was coupled with PAO1-subtractive hybridization.
      Three loci were found within the genomes of two CF isolates encoding one novel
      homolog involved in retaining a Shigella virulence plasmid (mvpTA) and two
      divergent genes that function in removing negative supercoiling (topA) and
      biosynthesis of pyoverdine (PA2402). Together, P. aeruginosa biodiversity could
      provide one cause for the variation of morbidity and mortality in CF. P.
      aeruginosa may possess undefined biofilm adhesins that are important to the
      development of an antibiofilm therapeutic target.

PMID- 14688091
TI  - Aggregation of Cryptococcus neoformans by surfactant protein D is inhibited by
      its capsular component glucuronoxylomannan.
AB  - Cryptococcus neoformans is an opportunistic pathogen invading the
      immunocompromised host. Infection starts with the inhalation of acapsular or
      sparsely encapsulated cells, after which capsule synthesis is initiated. The
      capsule is the main virulence factor of this yeast-like fungus. Pulmonary
      surfactant protein D (SP-D) is an important component of the local innate defense
      system. In the present study, interactions of SP-D with intact C. neoformans
      cells and their isolated capsular components were investigated. Although
      encapsulated cryptococci were bound, SP-D showed the highest affinity for
      acapsular C. neoformans. Only acapsular cryptococci were aggregated by SP-D.
      Furthermore, the cryptococcal capsular components glucuronoxylomannan (GXM) and
      mannoprotein 1 (MP1) were bound with relatively high affinity, in contrast to
      GalXM and MP2. Binding as well as aggregation of acapsular C. neoformans by SP-D
      could be inhibited by GXM in concentrations that are likely to be present in the
      lung after infection, suggesting that not only the capsule hampers SP-D function
      within the innate defense system of the lung but also the secreted capsular
      component GXM.

PMID- 14688092
TI  - Apical membrane antigen 1, a major malaria vaccine candidate, mediates the close
      attachment of invasive merozoites to host red blood cells.
AB  - Apical membrane antigen 1 (AMA-1) of Plasmodium merozoites is established as a
      candidate molecule for inclusion in a human malaria vaccine and is strongly
      conserved in the genus. We have investigated its function in merozoite invasion
      by incubating Plasmodium knowlesi merozoites with red cells in the presence of a
      previously described rat monoclonal antibody (MAb R31C2) raised against an
      invasion-inhibitory epitope of P. knowlesi AMA-1 and then fixing the material for
      ultrastructural analysis. We have found that the random, initial, long-range (12
      nm) contact between merozoites and red cells occurs normally in the presence of
      the antibody, showing that AMA-1 plays no part in this stage of attachment.
      Instead, inhibited merozoites fail to reorientate, so they do not bring their
      apices to bear on the red cell surface and do not make close junctional apical
      contact. We conclude that AMA-1 may be directly responsible for reorientation or
      that the molecule may initiate the junctional contact, which is then presumably
      dependent on Duffy binding proteins for its completion.

PMID- 14688093
TI  - Delayed clearance of Ehrlichia chaffeensis infection in CD4+ T-cell knockout
      mice.
AB  - Human monocytic ehrlichiosis is an emerging tick-borne disease caused by the
      rickettsia Ehrlichia chaffeensis. To examine the role of helper T cells in host
      resistance to this macrophage-tropic bacterium, we assessed E. chaffeensis
      infections in three mouse strains with differing functional levels of helper T
      cells. Wild-type, C57BL/6J mice resolved infections in approximately 2 weeks.
      Major histocompatibility complex class II (MHCII) knockout, B6.129-Abb(tm1) mice
      lacking helper T cells developed persistent infections that were not resolved
      even after several months. CD4+ T-cell-deficient, B6.129S6-Cd4(tm1Knw) mice
      cleared the infection, but the clearance took 2 weeks longer than it did for wild
      type mice. C57BL/6J mice resolved infection more rapidly following a second
      experimental challenge, but B6.129S6-Cd4(tm1Knw) mice did not. The B6.129S6
      Cd4(tm1Knw) mice also developed active E. chaffeensis-specific immunoglobulin G
      responses that were slightly lower in concentration and slower to develop than
      that observed in C57BL/6J mice. E. chaffeensis-specific cytotoxic T cells were
      not detected following a single bacterial challenge in any mouse strain,
      including wild-type C57BL/6J mice. However, the cytotoxic T-cell activity
      developed in all three mouse strains, including the MHCII and CD4+ T-cell
      knockouts, when challenged with a second E. chaffeensis infection. The data
      reported here suggest that the cell-mediated immunity, orchestrated by CD4+ T
      cells is critical for conferring rapid clearance of E. chaffeensis.

PMID- 14688094
TI  - Plant cell-based intimin vaccine given orally to mice primed with intimin reduces
      time of Escherichia coli O157:H7 shedding in feces.
AB  - Intimin is the primary adhesin of Escherichia coli O157:H7, the most common
      infectious cause of bloody diarrhea in the United States and the leading cause of
      acute kidney failure in children who develop hemolytic uremic syndrome. Cattle
      are the primary reservoir of E. coli O157:H7. Indeed, most cases of E. coli
      O157:H7 infection in the United States occur after ingestion of contaminated
      undercooked hamburger or produce that had contact with bovine manure. Because
      intimin is required for persistent colonization of neonatal calves and adult
      cattle, we hypothesized that an intimin-based vaccination strategy in calves
      would reduce colonization of cattle with E. coli O157:H7. To test this concept in
      a small-animal model, we developed transgenic tobacco plant cells that express
      the carboxy-terminal host cell-binding domain of E. coli O157:H7 intimin. Mice
      were either immunized intraperitoneally with intimin expressed from the plant
      cells, fed transgenic plant cells, or both. Here we show that these mice
      generated an intimin-specific mucosal immune response when primed parenterally
      and then boosted orally and also exhibited a reduced duration of E. coli O157:H7
      fecal shedding after challenge.

PMID- 14688095
TI  - Role of Toll-like receptor 4 in induction of cell-mediated immunity and
      resistance to Brucella abortus infection in mice.
AB  - Initial host defense to bacterial infection is executed by innate immunity, and
      therefore the main goal of this study was to examine the contribution of Toll
      like receptors (TLRs) during Brucella abortus infection. CHO reporter cell lines
      transfected with CD14 and TLRs showed that B. abortus triggers both TLR2 and
      TLR4. In contrast, lipopolysaccharide (LPS) and lipid A derived from Brucella
      rough (R) and smooth (S) strains activate CHO cells only through TLR4.
      Consistently, macrophages from C3H/HePas mice exposed to R and S strains and
      their LPS produced higher levels of tumor necrosis factor alpha (TNF-alpha) and
      interleukin-12 compared to C3H/HeJ, a TLR4 mutant mouse. The essential role of
      TLR4 for induction of proinflammatory cytokines was confirmed with diphosphoryl
      lipid A from Rhodobacter sphaeroides. Furthermore, to determine the contribution
      of TLR2 and TLR4 in bacterial clearance, numbers of Brucella were monitored in
      the spleen of C3H/HeJ, C3H/HePas, TLR2 knockout, and wild-type mice at 1, 3, and
      6 weeks following B. abortus infection. Interestingly, murine brucellosis was
      markedly exacerbated at weeks 3 and 6 after infection in animals that lacked
      functional TLR4 (C3H/HeJ) compared to C3H/HePas that paralleled the reduced gamma
      interferon production by this mouse strain. Finally, by mass spectrometry
      analysis we found dramatic differences on the lipid A profiles of R and S
      strains. In fact, S lipid A was shown to be more active to trigger TLR4 than R
      lipid A in CHO cells and more effective in inducing dendritic cell maturation. In
      conclusion, these results indicate that TLR4 plays a role in resistance to B.
      abortus infection and that S lipid A has potent adjuvant activity.

PMID- 14688096
TI  - Immunization of female mice with glycoconjugates protects their offspring against
      encapsulated bacteria.
AB  - The immune system of the newborn is immature, and therefore it is difficult to
      induce protective immunity by vaccination in the neonatal period. Immunization of
      mothers during pregnancy against infections caused by encapsulated bacteria could
      thus be particularly attractive, as infants do not respond to polysaccharide (PS)
      antigens. Transmission of maternal vaccine-specific antibodies and protection of
      offspring against pneumococcal bacteremia and/or lung infection were studied in a
      neonatal murine model of pneumococcal immunization and infections. Adult female
      mice were immunized with native pneumococcal PS (PPS) of serotypes 1, 6B, and 19F
      or PPS conjugated to tetanus protein (Pnc-TT), and PPS-specific antibodies were
      measured in sera of mothers and their offspring. Effective transmission of
      maternal antibodies was observed, as PPS-specific immunoglobulin G levels in 3
      week-old offspring of immunized mothers were 37 to 322% of maternal titers, and a
      significant correlation between maternal and offspring antibody levels was
      observed. The PPS-specific antibodies persisted for several weeks but slowly
      decreased over time. Offspring of Pnc-TT-immunized mothers were protected against
      pneumococcal infections with homologous serotypes, whereas PPS immunization of
      mothers did not protect their offspring, in agreement with the low titer of
      maternal PPS specific antibodies. When adult female mice were immunized with a
      meningococcal serogroup C conjugate vaccine (MenC-CRM), antibody response and
      transmission were similar to those observed for pneumococcal antibodies.
      Importantly, bactericidal activity was demonstrated in offspring of MenC-CRM
      immunized mothers. These results demonstrate that this murine model of
      pneumococcal immunization and infections is suitable to study maternal
      immunization strategies for protection of offspring against encapsulated
      bacteria.

PMID- 14688098
TI  - Biological activities of naturally occurring antibodies reactive with Candida
      albicans mannan.
AB  - Sera from normal adult humans may contain high levels of antibody reactive with
      Candida albicans mannan. This study examined selected biological activities of
      such antibodies, focusing on sera that were collected from 34 donors and analyzed
      individually. The results showed that antimannan titers were normally
      distributed. Reactivity as determined by enzyme-linked immunosorbent assay with
      serotype A mannan generally paralleled reactivity with serotype B. Analysis of
      the kinetics for activation of the complement system and deposition of complement
      component 3 (C3) onto serotype A and serotype B cells showed a decrease in the
      lag time that occurred before the onset of rapid accumulation of C3 that
      correlated with increasing antimannan titers. In contrast, there was a decrease
      in the overall rate of accumulation of C3 on serotype A cells that was strongly
      correlated with increasing antibody titers; serotype B cells showed no such
      decrease. An evaluation of the contribution of mannan antibody to
      opsonophagocytic killing showed that mannan antibody in individual sera and
      antimannan immunoglobulin G (IgG) affinity purified from human plasma contributed
      to killing by neutrophils in a dose-dependent fashion in the absence of a
      functional complement system. However, affinity-purified antibody in very high
      concentrations was inhibitory to both complement-dependent and complement
      independent opsonophagocytosis, and this finding suggests a prozone-like effect.
      In contrast, if the complement system was functional, antimannan IgG was not
      needed for opsonophagocytic killing. These results suggest that naturally
      occurring mannan antibodies and the complement system are functionally redundant
      for opsonophagocytic killing by neutrophils.

PMID- 14688097
TI  - Immunogenicity and efficacy of Cryptococcus neoformans capsular polysaccharide
      glucuronoxylomannan peptide mimotope-protein conjugates in human immunoglobulin
      transgenic mice.
AB  - Peptide mimotopes of capsular polysaccharides have been proposed as antigens for
      vaccines against encapsulated pathogens. In this study, we determined the
      antibody response to and efficacy of P13, a peptide mimetic of the Cryptococcus
      neoformans capsular polysaccharide glucuronoxylomannan (GXM), in mice that
      produce human antibodies. P13 was conjugated to tetanus toxoid (TT) or diphtheria
      toxoid (DT) and administered subcutaneously in Alhydrogel with or without CpG to
      mice transgenic for human immunoglobulin loci (XenoMouse mice) and expressing
      either immunoglobulin G2 (IgG2) (G2 mice) or IgG4 (G4 mice). Mice were vaccinated
      and revaccinated two or three times. The serum antibody responses of the mice to
      GXM and P13 and antibody idiotype expression were analyzed by an enzyme-linked
      immunosorbent assay. The results showed that both P13-TT and P13-DT were
      antigenic, inducing a mimetic response to P13 in both G2 and G4 mice, and
      immunogenic, inducing a mimotope response including VH3 (idiotype)-positive
      antibodies to GXM in G2 but not G4 mice. CpG led to higher titers of IgG to P13
      and GXM in P13-TT-vaccinated G2 mice. C. neoformans challenge of P13-protein
      conjugate-vaccinated and control G2 mice induced anamnestic IgG- and VH3-positive
      responses to GXM and was associated with a significantly decreased risk of death
      and a prolongation of survival in P13-DT-vaccinated mice compared to phosphate
      buffered saline-treated or protein carrier-vaccinated mice. These findings reveal
      that P13 elicited a human antibody response with VH3 expression in human
      immunoglobulin transgenic mice that has been observed for human antibodies to GXM
      and support the concept that peptide mimotope-based vaccines may hold promise for
      the treatment of C. neoformans infections.

PMID- 14688099
TI  - Camelysin is a novel surface metalloproteinase from Bacillus cereus.
AB  - Bacillus cereus frequently causes food poisoning or nosocomial diseases.
      Vegetative cells express the novel surface metalloproteinase camelysin (casein
      cleaving metalloproteinase) during exponential growth on complex, peptide-rich
      media. Camelysin is strongly bound to the cell surface and can be solubilized
      only by detergents or butanol. Camelysin spontaneously migrates from the surface
      of intact bacterial cells to preformed liposomes. The complete sequence of the
      camelysin-encoding gene, calY, was determined by reverse PCR on the basis of the
      N-terminal sequence and some internal tryptic cleavage peptides. The calY gene
      codes for a polypeptide of 21.569 kDa with a putative signal peptide of 27 amino
      acids (2.513 kDa) preceding the mature protein (19.056 kDa). Although the
      predicted amino acid sequence of CalY does not exhibit a typical metalloprotease
      consensus sequence, high-pressure liquid chromatography-purified camelysin
      contains one zinc ion per protein molecule. Matrix-assisted laser desorption
      ionization-time-of-flight mass spectrometry and tryptic peptide mass
      fingerprinting confirmed the identity of this zinc-binding protein as CalY.
      Disruption of the calY gene results in a strong decrease in the cell-bound
      proteolytic activity on various substrates.

PMID- 14688100
TI  - Melanin from Fonsecaea pedrosoi induces production of human antifungal antibodies
      and enhances the antimicrobial efficacy of phagocytes.
AB  - Fonsecaea pedrosoi is a fungal pathogen that produces melanin. The functions of
      melanin and its possible influence in the protective immunological response
      during infection by F. pedrosoi are not known. In this work, treatment of F.
      pedrosoi mycelia with proteases and glycosidases followed by a denaturing agent
      and hot concentrated acid left a black residue. Scanning electron microscopy
      demonstrated that this processed melanized residue resembled very closely the
      intact mycelium in shape and size. Melanin particles were also isolated from
      culture fluids of conidia or sclerotic forms of F. pedrosoi. Secreted melanins
      were reactive with sera from infected human patients, suggesting that F. pedrosoi
      synthesizes melanin in vivo. The antibodies against melanin were purified from
      patients' sera and analyzed by indirect immunofluorescence. They reacted with
      sclerotic cells from patients' lesions as well as with sclerotic bodies
      cultivated in vitro, conidia, mycelia, and digested residues. Treatment of F.
      pedrosoi with purified antibodies against melanin inhibited fungal growth in
      vitro. The interaction of F. pedrosoi with phagocytes in the presence of melanin
      resulted in higher levels of fungal internalization and destruction by host
      cells, which was accompanied by greater degrees of oxidative burst. Taken
      together, these results indicate that melanin from F. pedrosoi is an
      immunologically active fungal structure that activates humoral and cellular
      responses that could help the control of chromoblastomycosis by host defenses.

PMID- 14688101
TI  - Single intranasal mucosal Mycobacterium bovis BCG vaccination confers improved
      protection compared to subcutaneous vaccination against pulmonary tuberculosis.
AB  - Whether the intranasal (i.n.) route of Mycobacterium bovis BCG vaccination
      provides better protection against pulmonary tuberculosis than subcutaneous
      (s.c.) vaccination remains an incompletely solved issue. In the present study, we
      compared both immune responses and protection elicited by single BCG vaccinations
      via the i.n. or s.c. route in BALB/c mice. While both i.n. and s.c. vaccination
      triggered comparable levels of primary immune activation in the spleen and
      draining lymph nodes, i.n. vaccination led to a greater antigen-specific gamma
      interferon recall response in splenocytes than s.c. vaccination upon secondary
      respiratory mycobacterial challenge, accompanied by an increased frequency of
      antigen-specific lymphocytes. There was also a quicker cellular response in the
      lungs of i.n. vaccinated mice upon mycobacterial challenge. Mice vaccinated i.n.
      were found to be much better protected, particularly in the lung, than s.c.
      vaccinated counterparts against pulmonary tuberculosis at both 3 and 6 months
      postvaccination. These results suggest that the i.n. route of vaccination
      improves the protective effect of the current BCG vaccine.

PMID- 14688102
TI  - Association between protection against clinical malaria and antibodies to
      merozoite surface antigens in an area of hyperendemicity in Myanmar:
      complementarity between responses to merozoite surface protein 3 and the 220
      kilodalton glutamate-rich protein.
AB  - We performed a longitudinal clinical and parasitological follow-up study in OoDo,
      a village in southeast Asia in which malaria is hyperendemic, in order to assess
      the association between protection against malaria attacks and antibodies to
      three currently evaluated vaccine candidates, merozoite surface protein 1 (MSP1),
      MSP3, and the 220-kDa glutamate-rich protein (GLURP) from Plasmodium falciparum.
      Our results showed that the levels of cytophilic immunoglobulin G3 (IgG3)
      antibodies against conserved regions of MSP3 and GLURP were significantly
      correlated with protection against clinical P. falciparum malaria. In contrast,
      the levels of noncytophilic IgG4 antibodies against GLURP increased with the
      number of malaria attacks. Furthermore, we observed a complementary effect of the
      MSP3- and GLURP-specific IgG3 antibodies in relation to malaria protection. In
      the individuals that did not respond to one of the antigens, a strong response to
      the other antigen was consistently detected and was associated with protection,
      suggesting that induction of antibodies against both MSP3 and GLURP could be
      important for the development of protective immunity. The complementarity of the
      responses to the two main targets of antibody-dependent cellular inhibition
      identified to date provides the first rational basis for combining these two
      antigens in a hybrid vaccine formulation.

PMID- 14688103
TI  - Induction of Plasmodium falciparum transmission-blocking antibodies in nonhuman
      primates by a combination of DNA and protein immunizations.
AB  - Malaria transmission-blocking vaccination can effectively reduce and/or eliminate
      transmission of parasites from the human host to the mosquito vector. The
      immunity achieved by inducing an antibody response to surface antigens of male
      and female gametes and parasite stages in the mosquito. Our laboratory has
      developed DNA vaccine constructs, based on Pfs25 (a Plasmodium falciparum surface
      protein of 25 kDa), that induce a transmission-blocking immune response in mice
      (C. A. Lobo, R. Dhar, and N. Kumar, Infect. Immun. 67:1688-1693, 1999). To
      evaluate the safety, immunogenicity, and efficacy of the Pfs25 DNA vaccine in
      nonhuman primates, we immunized rhesus macaques (Macaca mulatta) with a DNA
      vaccine plasmid encoding Pfs25 or a Pfg27-Pfs25 hybrid or with the plasmid (empty
      plasmid) alone. Immunization with four doses of these DNA vaccine constructs
      elicited antibody titers that were high but nonetheless unable to reduce the
      parasite's infectivity in membrane feeding assays. Further boosting of the
      antibody response with recombinant Pfs25 formulated in Montanide ISA-720
      increased antibody titers (30-fold) and significantly blocked transmission of P.
      falciparum gametocytes to Anopheles mosquitoes (approximately 90% reduction in
      oocyst numbers in the midgut). Our data show that a DNA prime-protein boost
      regimen holds promise for achieving transmission-blocking immunity in areas where
      malaria is endemic and could be effective in eradicating malaria in isolated
      areas where the level of malaria endemicity is low.

PMID- 14688104
TI  - L-serine catabolism via an oxygen-labile L-serine dehydratase is essential for
      colonization of the avian gut by Campylobacter jejuni.
AB  - Campylobacter jejuni is a microaerophilic, asaccharolytic bacterium. The identity
      of the carbon and energy sources used by C. jejuni in vivo is unknown, but the
      genome sequence of strain NCTC11168 indicates the presence of genes for
      catabolism of a limited range of amino acids, including serine. Specific omission
      of L-serine from a defined medium containing a mixture of amino acids led to a
      dramatic decrease in cell yields. As C. jejuni does not have a biosynthetic
      serine requirement, this supports earlier suggestions that L-serine is a
      preferentially catabolized amino acid. Serine transport was found to be mediated
      by at least two systems in strain 11168; a high-capacity, low-affinity L-serine
      specific system encoded by Cj1625c (sdaC) and a higher-affinity L-serine/L
      threonine system responsible for residual L-serine transport in an sdaC mutant.
      Catabolism of L-serine to pyruvate and ammonia is carried out by SdaA (encoded by
      Cj1624c), which was overexpressed, purified, and shown to be an oxygen-labile
      iron-sulfur enzyme. L-Serine dehydratase activity in an sdaA mutant was reduced
      10-fold compared to that in the wild type, but the residual activity (due to the
      anabolic L-threonine dehydratase) could not support either growth on or
      utilization of L-serine in defined media. However, although sdaA mutants showed
      no obvious growth defect in complex media, they completely failed to colonize 3
      week-old chickens as assayed both by cloacal swabs taken over a 6-week period and
      by cecal colony counts postmortem. In contrast, the isogenic parent strain
      colonized chickens to high levels within 1 week of inoculation. The results show
      that an active SdaA is essential for colonization of the avian gut by C. jejuni
      and imply that catabolism of L-serine is crucially important for the growth of
      this bacterium in vivo.

PMID- 14688105
TI  - Tumor necrosis factor alpha enhances Actinobacillus actinomycetemcomitans
      leukotoxin-induced HL-60 cell apoptosis by stimulating lymphocyte function
      associated antigen 1 expression.
AB  - We demonstrated previously that Actinobacillus actinomycetemcomitans leukotoxin
      (Ltx) is greatly able to induce apoptotic signaling in cells that are positive
      for lymphocyte function-associated antigen 1 (LFA-1), a cell receptor of Ltx. We
      investigated in this study whether inflammatory cytokines can regulate apoptosis
      of human leukemic HL-60 cells induced by Ltx. Of the cytokines tested, tumor
      necrosis factor alpha (TNF-alpha) significantly enhanced the Ltx-induced cell
      apoptosis. Northern and Western blotting analyses showed that TNF-alpha enhanced
      the expression of CD11a in the cells at both the mRNA and protein levels but did
      not do so for CD18 expression. TNF-alpha also enhanced the binding of Ltx to the
      cells. We also observed by measuring the mitochondrial transmembrane potential
      and the generation of superoxide anion that the cytokine enhanced Ltx-induced
      apoptosis in HL-60 cells. In addition, interleukin-1beta significantly enhanced
      Ltx-induced cell apoptosis, although the enhancing activity was lower than that
      of TNF-alpha. These stimulatory effects of both cytokines were also observed for
      human polymorphonuclear leukocytes. The ability of TNF-alpha to increase cell
      susceptibility to Ltx could be inhibited by preincubation of the cells with a
      monoclonal antibody against TNF receptor 1 but not by preincubation of the cells
      with a monoclonal antibody against anti-TNF receptor 2. Furthermore, the results
      of an assay of caspase 3 intracellular activity (PhiPhiLuxG1D2) showed that Ltx
      induced caspase 3 activation was completely neutralized by CD18 antibody
      treatment, although significant neutralization was also observed with anti-CD11a
      antibody. Taken together, the results of the present study indicate that TNF
      alpha acts as a potent stimulator of Ltx-induced HL-60 cell apoptosis via TNF
      receptor 1-mediated upregulation of LFA-1 expression.

PMID- 14688106
TI  - Immunogenicity of gonococcal transferrin binding proteins during natural
      infections.
AB  - In this study, we examined the immune response during gonococcal infection to the
      individual transferrin binding proteins by using a quantitative enzyme-linked
      immunosorbent assay (ELISA). Recombinant transferrin binding protein A (rTbpA)
      and rTbpB were purified under nondenaturing conditions for use as ELISA antigens.
      Sera and secretions from culture-positive individuals were analyzed for
      antibodies to rTbpA and rTbpB and compared to samples from individuals with no
      history of gonococcal infection. Although antibodies to both rTbpA and rTbpB were
      detected in serum, in most cases the antibody levels were not significantly
      different from those measured in the control population. Also, previous history
      of gonococcal infection did not increase antibody levels in serum, suggesting the
      lack of an anamnestic response. Analysis of secretion samples revealed antibody
      levels that were generally below the limits of detection in our assay. Overall,
      this study demonstrated a paucity of systemic and local antibody responses to
      rTbps as a result of natural infection and represents a baseline over which a
      protective antibody response will have to be generated in order to develop an
      efficacious gonococcal vaccine.

PMID- 14688107
TI  - Immunoglobulin G isotype responses to variant surface antigens of Plasmodium
      falciparum in healthy Gabonese adults and children during and after successive
      malaria attacks.
AB  - We assessed immunoglobulin G (IgG) isotype responses with specificity for the
      variant surface antigens (VSA) of heterologous Plasmodium falciparum isolates by
      using flow cytometry and plasma from healthy Gabonese adults and from children
      during and after two consecutive malaria episodes. The individual isolate
      specific antibody profiles differed markedly in terms of their isotype content
      but were similar for healthy adults and healthy uninfected children. In healthy
      adults, IgG3 and IgG2 responses were the highest, while in healthy children, IgG3
      and IgG4 predominated. A transiently elevated IgG1 response was observed during
      the second of two successive malaria episodes in children, signaling P.
      falciparum infection-induced cross-reactive anti-VSA responses. Our findings
      highlight the prominence of IgG3 in the overall profile of these responses but
      also indicate a marked age-related increase in the prevalence of anti-VSA
      antibodies of the classically noncytophilic IgG2 isotype, possibly reflecting the
      high frequency of the histidine-131 variant of FcgammaRIIA in the Gabonese
      population.

PMID- 14688108
TI  - Interleukin-18 is an essential element in host resistance to experimental group B
      streptococcal disease in neonates.
AB  - Previous studies demonstrated that interleukin-12 (IL-12)-dependent gamma
      interferon (IFN-gamma) responses have a major role in restricting in vivo
      bacterial growth during infection of mice with group B streptococci (GBS),
      important human pathogens. Like IL-12, IL-18 is a potent IFN-gamma inducer. The
      role of IL-18 in experimental GBS infection was investigated here. Significant
      elevations of IL-18 levels over baseline values were detected in plasma samples
      from neonatal mice rendered septic with GBS. Neutralization of IL-18
      significantly increased mortality and bacterial burden (P < 0.05). In contrast,
      administration of recombinant IL-18 (rIL-18) before or after GBS challenge
      remarkably improved survival and decreased blood colony counts, in association
      with increased IFN-gamma production by spleen cells. The beneficial effects of
      rIL-18 were counteracted by administration of neutralizing anti-IFN-gamma
      monoclonal antibodies, indicating that the effects of IL-18 were mediated by IFN
      gamma. Finally, low rIL-18 doses that had no effect of their own on bacterial
      burden could act in synergy with rIL-12 to protect neonatal mice during GBS
      infection. Collectively, our data indicate that IL-18 responses have an important
      role in host defenses against GBS and that rIL-18 may be useful in alternative
      strategies to treat neonatal GBS disease.

PMID- 14688109
TI  - Effects of anti-endothelial cell antibodies in leprosy and malaria.
AB  - As a result of damaging endothelial cells (ECs), Mycobacterium leprae triggers
      the production of antibodies (Abs). These anti-EC Abs (AECAs) can be divided into
      two types. The first type nonspecifically reacts with components of the cytosol
      (CY) and can be detected by enzyme-linked immunosorbent assay (ELISA). The second
      specifically reacts with the EC membrane (MB) and requires fluorescence-activated
      cell sorter (FACS) analysis to be detected. The presence of both types of AECAs
      was determined in 68 leprosy patients. The ELISA was positive for 35 of them but
      also for 30 of 34 malaria patients and 17 of 50 healthy African controls.
      However, whereas FACS analysis showed MB reactivity in only three malaria
      patients and four controls, this reactivity was found in 27 leprosy patients,
      more of those having the lepromatous than the tuberculoid form. Specificity for
      MB, which we failed to absorb by incubation with CY lysates, predominated over
      that for CY in leprosy, unlike malaria, where the EC reactivity was restricted to
      the CY. Western blot analysis and two-dimensional electrophoresis revealed that
      calreticulin, vimentin, tubulin, and heat shock protein 70 were targeted by AECAs
      from leprosy patients, but other proteins remained unidentified. These auto-Abs,
      but not those from malaria patients, did activate ECs, as indicated by the E
      selectin and intercellular adhesion molecule 1 upregulation, and/or induced them
      into apoptosis, as documented by four different methods. Our findings suggest
      that, in some but not all leprosy patients, AECAs may play a role in
      pathogenesis.

PMID- 14688111
TI  - Mice deficient in interleukin-4 (IL-4) or IL-4 receptor alpha have higher
      resistance to sporozoite infection with Plasmodium berghei (ANKA) than do naive
      wild-type mice.
AB  - BALB/c interleukin-4 (IL-4(-/-)) or IL-4 receptor-alpha (IL-4ralpha(-/-))
      knockout (KO) mice were used to assess the roles of the IL-4 and IL-13 pathways
      during infections with the blood or liver stages of plasmodium in murine malaria.
      Intraperitoneal infection with the blood-stage erythrocytes of Plasmodium berghei
      (ANKA) resulted in 100% mortality within 24 days in BALB/c mice, as well as in
      the mutant mouse strains. However, when infected intravenously with the
      sporozoite liver stage, 60 to 80% of IL-4(-/-) and IL-4ralpha(-/-) mice survived,
      whereas all BALB/c mice succumbed with high parasitemia. Compared to infected
      BALB/c controls, the surviving KO mice showed increased NK cell numbers and
      expression of inducible nitric oxide synthase (iNOS) in the liver and were able
      to eliminate parasites early during infection. In vivo blockade of NO resulted in
      100% mortality of sporozoite-infected KO mice. In vivo depletion of NK cells also
      resulted in 80 to 100% mortality, with a significant reduction in gamma
      interferon (IFN-gamma) production in the liver. These results suggest that IFN
      gamma-producing NK cells are critical in host resistance against the sporozoite
      liver stage by inducing NO production, an effective killing effector molecule
      against Plasmodium. The absence of IL-4-mediated functions increases the
      protective innate immune mechanism identified above, which results in immunity
      against P. berghei infection in these mice, with no major role for IL-13.

PMID- 14688110
TI  - Legionella pneumophila type II protein secretion promotes virulence in the A/J
      mouse model of Legionnaires' disease pneumonia.
AB  - Legionella pneumophila, the gram-negative agent of Legionnaires' disease,
      possesses type IV pili and a type II protein secretion (Lsp) system, both of
      which are dependent upon the PilD prepilin peptidase. By analyzing multiple pilD
      mutants and various types of Lsp mutants as well as performing trans
      complementation of these mutants, we have confirmed that PilD and type II
      secretion genes are required for L. pneumophila infection of both amoebae and
      human macrophages. Based upon a complete analysis of lspDE, lspF, and lspG
      mutants, we found that the type II system controls the secretion of protease,
      RNase, lipase, phospholipase A, phospholipase C, lysophospholipase A, and
      tartrate-sensitive and tartrate-resistant acid phosphatase activities and
      influences the appearance of colonies. Examination of the developing L.
      pneumophila genome database indicated that the organism has two other loci (lspC
      and lspLM) that are predicted to promote secretion and thus a set of genes that
      is comparable to the type II secretion genes in other gram-negative bacteria. In
      contrast to lsp mutants, L. pneumophila pilus mutants lacking either the PilQ
      secretin, the PspA pseudopilin, or pilin were not defective for colonial growth,
      secreted activities, or intracellular replication. L. pneumophila dot/icm mutants
      were also not impaired for type II-dependent exoenzymes. Upon intratracheal
      inoculation into A/J mice, lspDE, lspF, and pilD mutants, but not pilus mutants,
      exhibited a reduced ability to grow in the lung, as measured by competition
      assays. The lspF mutant was also defective in an in vivo kinetic assay.
      Examination of infected mouse sera revealed that type II secreted proteins are
      expressed in vivo. Thus, the L. pneumophila Lsp system is a virulence factor and
      the only type II secretion system linked to intracellular infection.

PMID- 14688112
TI  - Immune response to meningococcal serogroup C conjugate vaccine in asplenic
      individuals.
AB  - Asplenic individuals are known to be at increased risk of infection with
      encapsulated bacteria. Recent United Kingdom recommendations stated that this at
      risk group should receive one dose of the meningococcal serogroup C conjugate
      (MCC) vaccine. However, the immune response of asplenic individuals to MCC
      vaccine is unknown. The immune response of asplenics (n = 130) to immunization
      with the MCC vaccine was investigated. Asplenic individuals had a significantly
      lower geometric mean titer (GMT) (157.8; 95% confidence interval [CI], 94.5 to
      263.3) of bactericidal antibody in serum (SBA) than an age-matched control group
      (n = 48) (1448.2; 95% CI, 751.1 to 2792.0). However, 80% of asplenic individuals
      achieved the proposed protective SBA titer of > or =8. No differences were
      observed between the two groups in the serogroup C-specific immunoglobulin G
      geometric mean concentration. A significant reduction in SBA GMT or the number of
      responders achieving an SBA titer of > or =8 was observed if the reason for
      splenectomy was a medical cause or if MCC vaccination occurred <10 years after
      splenectomy. Individuals (n = 29) who did not achieve an SBA titer of > or =16
      were offered a second dose of MCC vaccine. Analysis of the SBA response revealed
      that 61% (14 of 23) of the individuals who received a second dose achieved a
      protective titer. In total, 93% of asplenic individuals achieved a titer of > or
      =8 following MCC vaccination (one or two doses combined). We recommend that,
      following vaccination of asplenics, either the level of functional antibody
      should be determined, with a second dose of MCC vaccine offered to nonresponders,
      or two doses of MCC vaccine should be routinely offered.

PMID- 14688113
TI  - Infection with an avirulent phoP mutant of Neisseria meningitidis confers broad
      cross-reactive immunity.
AB  - Successful vaccines against serogroup A and C meningococcal strains have been
      developed, but current serogroup B vaccines provide protection against only a
      limited range of strains. The ideal meningococcal vaccine would provide cross
      reactive immunity against the variety of strains that may be encountered in any
      community, but it is unclear whether the meningococcus possesses immune targets
      that have the necessary level of cross-reactivity. We have generated a phoP
      mutant of the meningococcus by allele exchange. PhoP is a component of a two
      component regulatory system which in other bacteria is an important regulator of
      virulence gene expression. Inactivation of the PhoP-PhoQ system in Salmonella
      leads to avirulence, and phoP mutants have been shown to confer protection
      against virulent challenge. These mutants have been examined as potential live
      attenuated vaccines. We here show that a phoP mutant of the meningococcus is
      avirulent in a mouse model of infection. Moreover, infection of mice with the
      phoP mutant stimulated a bactericidal immune response that not only killed the
      infecting strain but also showed cross-reactive bactericidal activity against a
      range of strains with different serogroup, serotype, and serosubtyping antigens.
      Sera from the mutant-infected mice contained immunoglobulin G that bound to the
      surface of a range of meningococcal strains and mediated opsonophagocytosis of
      meningococci by human phagocytic cells. The meningococcal phoP mutant is thus a
      candidate live, attenuated vaccine strain and may also be used to identify cross
      reactive protective antigens in the meningococcus.

PMID- 14688114
TI  - Vaccination with attenuated Neisseria meningitidis strains protects against
      challenge with live Meningococci.
AB  - Meningococcal disease is a life-threatening infection caused by Neisseria
      meningitidis. Currently, there are no vaccines to prevent infection with
      serogroup B N. meningitidis strains, the leading cause of meningococcal
      meningitis in Europe and North America. Here we describe the construction and
      characterization of two attenuated serogroup B N. meningitidis strains, YH102
      (MC58deltasia deltarfaF) and YH103 (MC58deltasia deltametH). Both strains are
      markedly attenuated in their capacity to cause bacteremia in rodent models and
      have a reduced ability to survive in a human whole-blood assay. Immunization of
      adult mice with these strains leads to the development of bactericidal antibodies
      and confers sterilizing protection against challenge with homologous live
      bacteria. Furthermore, we show that the strains confer protection against
      infection by other serogroups. Use of the attenuated strains in animals with gene
      knockouts or after depletion of immunological effectors could be used to define
      the basis of protection, and human volunteer studies could be undertaken to
      examine the immune response following exposure to this important human pathogen.

PMID- 14688115
TI  - Innate immune response of oral and foreskin keratinocytes: utilization of
      different signaling pathways by various bacterial species.
AB  - The innate immune response is critical for the epithelial antimicrobial barrier.
      The human beta-defensins are small, cationic antimicrobial peptides that are made
      by epithelial cells and that play a role in mucosal and skin defenses. Human beta
      defensin 1 (hBD-1) is expressed constitutively in epithelial tissues, whereas hBD
      2 and hBD-3 are expressed in response to bacterial stimuli or inflammation.
      Previous studies showed that hBD-2 was induced by Fusobacterium nucleatum cell
      wall extract without the involvement of the NF-kappaB transcription factors,
      which typically are associated with innate immunity and inflammation. The goal of
      this study was to characterize signaling pathways involved in hBD-2 induction in
      response to commensal and pathogenic bacteria. Cultured human oral and foreskin
      keratinocytes were treated separately with inhibitors of NF-kappaB, c-Jun N
      terminal kinase (JNK), and p38 and then stimulated with oral commensal
      Streptococcus gordonii, oral pathogens Porphyromonas gingivalis and
      Actinobacillus actinomycetemcomitans, skin commensal Staphylococcus epidermidis,
      or skin pathogen Streptococcus pyogenes. Different bacteria induced different
      levels of hBD-2 and in response to the various inhibitors tested, although
      certain common patterns were observed for commensal- and pathogen-stimulated
      cells. hBD-2 induction by all bacteria tested was partially or completely blocked
      by inhibitors of the JNK and p38 pathways. However, in addition, hBD-2 induction
      by pathogenic bacteria in both oral and foreskin keratinocytes was blocked by
      inhibitors of NF-kappaB. The results indicate that commensal and pathogenic
      bacteria utilize different pathways in hBD-2 induction and suggest that
      epithelial cells from different body sites have common signaling mechanisms to
      distinguish between commensal and pathogenic bacteria.

PMID- 14688116
TI  - Intracellular growth of Trypanosoma cruzi in cardiac myocytes is inhibited by
      cytokine-induced nitric oxide release.
AB  - The effect of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF
      alpha), and gamma interferon (IFN-gamma) on Trypanosoma cruzi multiplication and
      nitric oxide (NO) production in cardiac myocytes was investigated. Cardiac
      myocyte cultures were obtained from neonatal Wistar rat hearts, infected with T.
      cruzi, and treated with IL-1beta, TNF-alpha, IFN-gamma, or N-monomethyl-L
      arginine (L-NAME) for 72 h. Parasite growth was calculated from the number of
      infected cells in Giemsa-stained smears. Nitric oxide production was determined
      with the Griess reagent. Inducible nitric oxide synthase (iNOS) expression by
      cardiac myocytes was detected by Western blot. The results showed that the
      percentages of cardiac myocytes containing T. cruzi amastigotes in cytokine
      treated cultures were significantly lower than in nontreated cultures. The
      addition of L-NAME reversed the inhibitory effect on parasite growth of IL-1beta
      and TNF-alpha but not of IFN-gamma. Nitrite levels released by T. cruzi-infected
      and noninfected cardiac myocyte cultures after 72 h of stimulation with IL-1beta
      were significantly higher than those produced upon treatment with TNF-alpha, IFN
      gamma, or medium alone, regardless of the infection status. Nitrite levels in TNF
      alpha-stimulated infected cultures were significantly higher than in untreated
      infected cultures and TNF-alpha-treated noninfected cultures. L-NAME inhibited IL
      1beta- but not TNF-alpha-induced NO production, indicating the presence of iNOS
      dependent and iNOS-independent mechanisms for NO formation in this experimental
      system. iNOS expression was detected in infected and noninfected cardiac myocytes
      stimulated with IL-1 beta and TNF-alpha but not with IFN-gamma. These results
      suggest an important role for cardiac myocytes and locally secreted cytokines in
      the control of parasite multiplication in T. cruzi-induced myocarditis.

PMID- 14688117
TI  - Plasminogen binding by group A streptococcal isolates from a region of
      hyperendemicity for streptococcal skin infection and a high incidence of invasive
      infection.
AB  - Reports of resurgence in invasive group A streptococcal (GAS) infections come
      mainly from affluent populations with infrequent exposure to GAS. In the Northern
      Territory (NT) of Australia, high incidence of invasive GAS disease is secondary
      to endemic skin infection, serotype M1 clones are rare in invasive infection, the
      diversity and level of exposure to GAS strains are high, and no particular
      strains dominate. Expression of a plasminogen-binding GAS M-like protein (PAM)
      has been associated with skin infection in isolates elsewhere (D. Bessen, C. M.
      Sotir, T. M. Readdy, and S. K. Hollingshead, J. Infect. Dis. 173:896-900, 1996),
      and subversion of the host plasminogen system by GAS is thought to contribute to
      invasion in animal models. Here, we describe the relationship between plasminogen
      binding capacity of GAS isolates, PAM genotype, and invasive capacity in 29 GAS
      isolates belonging to 25 distinct strains from the NT. In the presence of
      fibrinogen and streptokinase, invasive isolates bound more plasminogen than
      isolates from uncomplicated infections (P < or = 0.004). Only PAM-positive
      isolates bound substantial levels of plasminogen by a fibrinogen-streptokinase
      independent pathway (direct binding). Despite considerable amino acid sequence
      variation within the A1 repeat region of PAM where the plasminogen-binding domain
      maps, the critical lysine residue was conserved.

PMID- 14688118
TI  - Neisseria meningitidis lipooligosaccharide structure-dependent activation of the
      macrophage CD14/Toll-like receptor 4 pathway.
AB  - Meningococcal lipopoly(oligo)saccharide (LOS) is a major inflammatory mediator of
      fulminant meningococcal sepsis and meningitis. Highly purified wild-type
      meningococcal LOS and LOS from genetically defined mutants of Neisseria
      meningitidis that contained specific mutations in LOS biosynthesis pathways were
      used to confirm that meningococcal LOS activation of macrophages was CD14/Toll
      like receptor 4 (TLR4)-MD-2 dependent and to elucidate the LOS structural
      requirement for TLR4 activation. Expression of TLR4 but not TLR2 was required,
      and antibodies to both TLR4 and CD14 blocked meningococcal LOS activation of
      macrophages. Meningococcal LOS alpha or beta chain oligosaccharide structure did
      not influence CD14/TLR4-MD-2 activation. However, meningococcal lipid A,
      expressed by meningococci with defects in 3-deoxy-D-manno-octulosonic acid (KDO)
      biosynthesis or transfer, resulted in an approximately 10-fold (P < 0.0001)
      reduction in biologic activity compared to KDO2-containing meningococcal LOS.
      Removal of KDO2 from LOS by acid hydrolysis also dramatically attenuated cellular
      responses. Competitive inhibition assays showed similar binding of glycosylated
      and unglycosylated lipid A to CD14/TLR4-MD-2. A decrease in the number of lipid A
      phosphate head groups or penta-acylated meningococcal LOS modestly attenuated
      biologic activity. Meningococcal endotoxin is a potent agonist of the macrophage
      CD14/TLR4-MD-2 receptor, helping explain the fulminant presentation of
      meningococcal sepsis and meningitis. KDO2 linked to meningococcal lipid A was
      structurally required for maximal activation of the human macrophage TLR4 pathway
      and indicates an important role for KDO-lipid A in endotoxin biologic activity.

PMID- 14688119
TI  - Immune responses to mycobacterial antigens in the Gambian population:
      implications for vaccines and immunodiagnostic test design.
AB  - Recombinant immunodominant mycobacterial antigens are needed for the development
      of new vaccines and immunodiagnostic tools for use against tuberculosis.
      Ubiquitous exposure to mycobacteria in tropical countries could influence vaccine
      induced immunity and the specificity of tuberculosis immunodiagnosis. For this
      study conducted in The Gambia, cellular immune responses to recombinant
      mycobacterial antigens were characterized in Mycobacterium bovis BCG-vaccinated
      and nonvaccinated infants, adult community controls, household contacts, health
      care workers, and tuberculosis patients. Neonatal BCG vaccination induced gamma
      interferon (IFN-gamma) responses to Mtb8.4, Mtb32-C, Mtb39A, Mtb9.9A, and Mtb32
      N, but not CFP-10 (Mtb11) and alpha-crystallin (Mtb16). Exposure to Mycobacterium
      tuberculosis in household contacts and health care workers was associated with
      high responses to CFP-10 and alpha-crystallin. Generally, low IFN-gamma responses
      were found in tuberculosis patients. These results suggest that Mtb8.4, Mtb32-C,
      Mtb39A, Mtb9.9A, and Mtb32-N may be used in a subunit vaccine to boost BCG
      induced immunity. While CFP-10 and alpha-crystallin are promising candidates for
      the immunodiagnosis of M. tuberculosis infection or for vaccine use, disease
      associated immunosuppression may prevent IFN-gamma immunodiagnosis of more
      advanced tuberculosis.

PMID- 14688120
TI  - Induction of interleukin-8 in T84 cells by Vibrio cholerae.
AB  - The induction of interleukin-8 (IL-8) in vitro has been suggested to correlate
      with the reactogenicity of Vibrio cholerae vaccine candidates. V. cholerae
      vaccine candidate 638, a hemagglutinin protease/hap-defective strain, was
      recently reported to be well tolerated in human volunteers, suggesting a role for
      Hap in reactogenicity. We examined the role of hap in the induction of IL-8 in
      intestinal epithelial T84 cells. Wild-type V. cholerae strains 3038 and C7258 and
      a vaccine candidate strain, JBK70, induced levels of IL-8 similar to those of
      their isogenic hap mutants. Supernatant containing Hap did not stimulate IL-8
      production at a variety of concentrations tested, suggesting that Hap itself does
      not induce IL-8 production. Furthermore, supernatant from CVD115, which had
      deletions of hap and rtxA (encoding repeats in toxin) and was derived from a
      reactogenic strain, CVD110, induced IL-8 production in T84 cells in a dose
      dependent manner. The IL-8-stimulating activity of CVD115 culture supernatants
      was growth phase dependent and was strongest in stationary phase cultures. This
      IL-8 stimulator(s) was resistant to heat treatment but sensitive to proteinase.
      Protease activity in vitro did not correlate with the reactogenicity of V.
      cholerae vaccine candidates. Our data suggest that Hap is not an IL-8 inducer in
      T84 cells and that the IL-8 stimulator in the supernatant of V. cholerae culture
      may play a role in reactogenicity.

PMID- 14688121
TI  - Both free-living and parasitic nematodes induce a characteristic Th2 response
      that is dependent on the presence of intact glycans.
AB  - Infection with parasitic nematodes is characterized by the induction of a
      profound type 2 immune response. We have studied the role of glycans in the
      induction of the skewed type 2 response by antigens of the parasitic nematode
      Brugia malayi as well as the free-living nematode Caenorhabditis elegans. Lymph
      node cells from BALB/c mice immunized with soluble extracts of the two nematodes
      showed distinct antigen-specific proliferation and cytokine production; however,
      both nematodes induced antigen-specific interleukin 4 (IL-4) production,
      demonstrating that the induction of a biased type 2 response is not unique to
      parasitic nematodes. Sodium periodate-treated soluble extracts of both nematodes
      consistently induced significantly less IL-4 production than the respective mock
      treated extracts, indicating that glycans play a critical role in the induction
      of the Th2 immune response by these nematodes. The glycan-dependent induction of
      the Th2-potentiating cytokine IL-4 occurs by 72 h postinoculation. Our data
      suggest that glycan determinants common to nematodes act as ligands, displaying
      distinct molecular patterns that trigger the immune system to launch a biased Th2
      immune response upon exposure to these organisms or their products. Further, the
      similarity of our findings to those for Schistosoma mansoni egg antigen is
      striking considering the enormous phylogenetic distance between nematodes and
      trematodes. These data thus have important implications for how the mammalian
      host responds to widely divergent metazoan invaders and suggest that the powerful
      C. elegans model system can be used to address these questions.

PMID- 14688122
TI  - Contribution of glutathione peroxidase to the virulence of Streptococcus
      pyogenes.
AB  - Glutathione peroxidases are widespread among eukaryotic organisms and function as
      a major defense against hydrogen peroxide and organic peroxides. However,
      glutathione peroxidases are not well studied among prokaryotic organisms and have
      not previously been shown to promote bacterial virulence. Recently, a gene with
      homology to glutathione peroxidase was shown to contribute to the antioxidant
      defenses of Streptococcus pyogenes (group A streptococcus). Since this bacterium
      causes numerous suppurative diseases that require it to thrive in highly inflamed
      tissue, it was of interest to determine if glutathione peroxidase is important
      for virulence. In this study, we report that GpoA glutathione peroxidase is the
      major glutathione peroxidase in S. pyogenes and is essential for S. pyogenes
      pathogenesis in several murine models that mimic different aspects of
      streptococcal suppurative disease. In contrast, glutathione peroxidase is not
      essential for virulence in a zebrafish model of streptococcal myositis, a disease
      characterized by the absence of an inflammatory cell infiltrate. Taken together,
      these data suggest that S. pyogenes requires glutathione peroxidase to adapt to
      oxidative stress that accompanies an inflammatory response, and the data provide
      the first demonstration of a role for glutathione peroxidase in bacterial
      virulence. The fact that genes encoding putative glutathione peroxidases are
      found in the genomes of many pathogenic bacterial species suggests that
      glutathione peroxidase may have a general role in bacterial pathogenesis.

PMID- 14688123
TI  - Gene expression in HL60 granulocytoids and human polymorphonuclear leukocytes
      exposed to Candida albicans.
AB  - Candida albicans is an opportunistic human pathogen causing both superficial and
      disseminated diseases. It is a dimorphic fungus, switching between yeast and
      hyphal forms, depending on cues from its microenvironment. Hyphae play an
      important role in the pathogenesis of candidiasis. The host's response to Candida
      infection is multifaceted and includes the participation of granulocytes as key
      effector cells. The aim of this investigation was to study host gene expression
      during granulocyte-Candida interaction. Effector cells were generated by the
      granulocytic differentiation of HL60 cells. The resulting cell population was
      shown to be morphologically and functionally equivalent to granulocytes and is
      therefore referred to as HL60 granulocytoids for the purposes of this study. Gene
      expression profiles were determined 1 h after hosts were infected with C.
      albicans. Three Candida-granulocytoid ratios were chosen to reflect different
      degrees of HL60 granulocytoid inhibition of C. albicans. The data demonstrate
      that at the high pathogen-host ratio, C. albicans modulated the HL60
      granulocytoid's response by downregulating the expression of known antimicrobial
      genes. In addition, looking at the expression of a large number of genes, not all
      of which have necessarily been implicated in candidastatic or candidacidal
      mechanisms, it has been possible to describe the physiological response of the
      HL60 granulocytoid to an infectious challenge with C. albicans. Finally, some of
      the observed changes in HL60 granulocytoid gene expression were investigated in
      freshly isolated human polymorphonuclear leukocytes infected with C. albicans.
      Similar changes were seen in these primary human cells, lending support to the
      validity of this model.

PMID- 14688124
TI  - Anthrax lethal toxin induces human endothelial cell apoptosis.
AB  - Because of its ease of dispersal and high lethality, Bacillus anthracis is one of
      the most feared biowarfare agents. A better understanding of anthrax pathogenesis
      is urgently needed to develop new therapies for systemic disease that is
      relatively unresponsive to antibiotics. Although experimental evidence has
      implicated a role for macrophages in anthrax pathogenesis, clinical and
      pathological observations suggest that a direct insult to the host vasculature
      may also be important. Two bacterial toxins, lethal toxin and edema toxin, are
      believed to mediate the clinical sequelae of anthrax. Here, I examined whether
      these toxins are directly toxic to endothelial cells, the cell type that lines
      the interior of blood vessels. I show for the first time that lethal toxin but
      not edema toxin reduces the viability of cultured human endothelial cells and
      induces caspase-dependent endothelial apoptosis. In addition, this toxicity
      affects both microvascular and large vessel endothelial cells as well as
      endothelial cells that have differentiated into tubules within a type I collagen
      extracellular matrix. Finally, lethal toxin induces cleavage of mitogen-activated
      protein kinase kinases in endothelial cells and inhibits phosphorylation of ERK,
      p38, and JNK p46. Based on the contributions of these pathways to endothelial
      survival, I propose that lethal toxin-mediated cytotoxicity/apoptosis results
      primarily through inhibition of the ERK pathway. I also hypothesize that the
      observed endothelial toxicity contributes to vascular pathology and hemorrhage
      during systemic anthrax.

PMID- 14688125
TI  - Brucella abortus rough mutants are cytopathic for macrophages in culture.
AB  - Rough mutants of Brucella spp. are attenuated for survival in animal models.
      However, conflicting in vitro evidence has been obtained concerning the
      intracellular survival of rough mutants. Transposon-derived rough mutants
      isolated in our laboratory were previously shown to exhibit small but significant
      reductions in intracellular survival in a 12-h in vitro assay. Several recent
      publications report that rough mutants exhibited increased macrophage uptake
      relative to their smooth parental strains, and a reduction in numbers at the end
      of the assay has been interpreted as intracellular killing. In an effort to
      explore the role of O antigen in the interaction between Brucella abortus and
      macrophages, we have monitored the uptake of rough mutants and survival in vitro
      by using the murine macrophage cell line J774.A1. The results confirm a 10- to 20
      fold-increased uptake of rough mutants over that of smooth organisms under
      standard conditions. Recovery of the rough mutants persisted up to 8 h
      postinfection, but at the point when intracellular replication of the smooth
      organisms was observed, the number of rough organisms recovered declined.
      Fluorescence microscopy revealed the intracellular multiplication of both smooth
      and rough organisms, and assays performed in the absence of antibiotic confirmed
      the replication of the rough organisms. Examination by phase-contrast microscopy
      revealed the lytic death of macrophages infected with the rough mutants, which
      was confirmed by the release of lactate dehydrogenase (LDH) from the cell
      cytoplasm. Thus, the decline in the number of rough organisms was the result of
      the lysis of macrophages and not from intracellular killing. The cytopathic
      effect is characterized as necrotic rather than apoptotic cell death based on
      early LDH release, annexin V and propidium iodide staining, morphological changes
      of infected cells and nuclei, and glycine protection. The cytopathic effect was
      observed with macrophages at multiplicities of infection (MOIs) of as low as 20
      and was not observed with epithelial cells at MOIs of as high as 2000. These
      findings suggest a role for O antigen during the early stages of host-agent
      interaction that is essential in establishing an intracellular niche that
      maintains and supports persistent intracellular infection resulting in disease.

PMID- 14688126
TI  - Chlamydia-infected cells continue to undergo mitosis and resist induction of
      apoptosis.
AB  - Both anti- and proapoptotic activities have been reported to occur during
      chlamydial infection. To reconcile the apparent controversy, we compared host
      cell apoptotic responses to infection with 17 different chlamydial serovars and
      strains. None of the serovars caused any biologically significant apoptosis in
      the infected host cells. Host cells in chlamydia-infected cultures can continue
      to undergo DNA synthesis and mitosis. Chlamydia-infected cells are resistant to
      apoptosis induction, although the extent of the antiapoptotic ability varied
      between serovars. These observations have demonstrated that an anti- but not
      proapoptotic activity is the prevailing event in chlamydia-infected cultures.

PMID- 14688127
TI  - Urokinase-deficient mice fail to generate a type 2 immune response following
      schistosomal antigen challenge.
AB  - Activated lymphocytes express urokinase-type plasminogen activator (uPA).
      Previous work suggests that uPA modulates T-lymphocyte responses. Mice deficient
      in uPA (uPA(-/-)) fail to generate type 1 (T1) immune responses during infection
      with Cryptococcus neoformans. Failure to generate either a T1 or a T2 immune
      response is not predictive of defects in the alternative response. Conversely,
      down-regulation of one type of immune response may result in inappropriate
      overactivation of the other. It is not known whether the immune defect in uPA(-/
      ) mice affects only T1 responses or whether T2 responses are also impaired.
      Impairment of both T1 and T2 responses would suggest a global T-cell defect in
      the absence of uPA. To determine the role of uPA in T2 immune responses, wild
      type (WT) and uPA(-/-) mice were primed and challenged with schistosomal egg
      antigen (SEA). This elicits strong polarization to T2 immune responses in
      immunocompetent mice. The challenged WT mice developed delayed-type
      hypersensitivity (DTH) to SEA; high levels of serum immunoglobulin E (IgE); a
      strong T2 cytokine phenotype with markedly elevated levels of interleukin-4 (IL
      4), IL-5, and IL-13; and eosinophil-rich pulmonary granulomas. uPA(-/-) mice
      failed to develop DTH to SEA; did not polarize Ig production to IgE; did not
      produce high levels of IL-4, IL-5, or IL-13; and had markedly reduced numbers of
      granuloma-associated eosinophils. uPA(-/-) mice fail to generate polarized T2
      immune responses to a T2-inducing pathogen. These findings, in conjunction with
      our previous work, demonstrate that mice deficient in uPA have profoundly
      impaired immunity involving both T1 and T2 polarization and are largely
      immunologically unresponsive.

PMID- 14688128
TI  - Role of neutrophils in murine salmonellosis.
AB  - Gastrointestinal infections with Salmonella enterica serovars have different
      clinical outcomes that range from localized inflammation to a life-threatening
      systemic disease in the case of typhoid fever. Using a mouse model of systemic
      salmonellosis, we investigated the contribution of neutrophils to the innate
      immune defense against Salmonella after oral infection. Neutrophil infiltration
      was dependent on the bacterial burden in various infected organs (Peyer's
      patches, mesenteric lymph nodes, spleen, and liver). However, the massive
      infiltration of neutrophils did not allow clearance of an infection with wild
      type Salmonella, presumably due to protection of intracellular Salmonella against
      neutrophil activities. A Salmonella mutant strain deficient in Salmonella
      pathogenicity island 2 (SPI2) was able to infect systemic sites, but its
      replication was highly restricted and it did not cause detectable attraction of
      neutrophils. Neutrophil depletion by antibody treatment of mice did not restore
      the virulence of SPI2 or auxotrophic mutant strains, supporting the hypothesis
      that attenuation of the strains is not due to greater susceptibility to
      neutrophil killing. Our observations reveal that neutrophils have completely
      different roles during systemic salmonellosis and localized gastrointestinal
      infections. In the latter conditions, rapid neutrophil attraction efficiently
      prevents the spread of the pathogen, whereas the neutrophil influx is delayed
      during systemic infections and cannot protect against lethal bacteremia.

PMID- 14688129
TI  - TraJ-dependent Escherichia coli K1 interactions with professional phagocytes are
      important for early systemic dissemination of infection in the neonatal rat.
AB  - Escherichia coli is a major cause of neonatal bacterial sepsis and meningitis. We
      recently identified a gene, traJ, which contributes to the ability of E. coli K1
      to penetrate the blood-brain barrier in the neonatal rat. Because very little is
      known regarding the most critical step in disease progression, translocation to
      the gut and dissemination to the lymphoid tissues after a natural route of
      infection, we assessed the ability of a traJ mutant to cause systemic disease in
      the neonatal rat. Our studies determined that the traJ mutant is significantly
      less virulent than the wild type in the neonatal rat due to a decreased ability
      to disseminate from the mesenteric lymph nodes to the deeper tissues of the liver
      and spleen and to the blood during the early stages of systemic disease.
      Histopathologic studies determined that although significantly less or no mutant
      bacteria were recovered from the spleen and livers of infected neonatal rats, the
      inflammatory response was considerably greater than that in wild-type-colonized
      tissues. In vitro studies revealed that macrophages internalize the traJ mutant
      less frequently than they do the wild type and by a morphologically distinct
      process. Furthermore, we determined that tissue macrophages and dendritic cells
      within the liver and spleen are the major cellular targets of E. coli K1 and that
      TraJ significantly contributes to the predominantly intracellular nature of E.
      coli K1 within these professional phagocytes exclusively during the early stages
      of systemic disease. These data indicate that, contrary to earlier indications,
      E. coli K1 resides within professional phagocytes, and this is essential for the
      efficient progression of systemic disease.

PMID- 14688130
TI  - Listeriosis in the pregnant guinea pig: a model of vertical transmission.
AB  - Feto-placental infections represent a major cause of pregnancy complications, and
      yet the underlying molecular and cellular mechanisms of vertical transmission are
      poorly understood. Listeria monocytogenes, a facultative intracellular pathogen,
      is one of a group of pathogens that are known to cause feto-placental infections
      in humans and other mammals. The purpose of this study was to evaluate possible
      mechanisms of vertical transmission of L. monocytogenes. Humans and guinea pigs
      have a hemochorial placenta, where a single layer of fetally derived trophoblasts
      separates maternal from fetal circulation. We characterized L. monocytogenes
      infection of the feto-placental unit in a pregnant guinea pig model and in
      primary human trophoblasts and trophoblast-derived cell lines. The clinical
      manifestations of listeriosis in the pregnant guinea pigs and the tropism of L.
      monocytogenes to the guinea pig placenta resembled those in humans. Trophoblast
      cell culture systems were permissive for listerial growth and cell-to-cell spread
      and revealed that L. monocytogenes deficient in internalin A, a virulence factor
      that mediates invasion of nonphagocytic cells, was 100-fold defective in
      invasion. However, crossing of the feto-placental barrier in the guinea pig model
      was independent of internalin A, suggesting a negligible role for internalin
      mediated direct invasion of trophoblasts in vivo. Further understanding of
      vertical transmission of L. monocytogenes will help in designing more effective
      means of treatment and disease prevention.

PMID- 14688132
TI  - Multiclonal Leishmania braziliensis population structure and its clinical
      implication in a region of endemicity for American tegumentary leishmaniasis.
AB  - In Corte de Pedra (CP), northeastern Brazil, Leishmania braziliensis causes three
      distinct forms of American tegumentary leishmaniasis (ATL). To test the
      hypothesis that strain polymorphism may be involved in this disease spectrum and
      accurately characterize the parasite population structure in CP, we compared one
      L. major, two non-CP L. braziliensis, one CP L. amazonensis, and 45 CP L.
      braziliensis isolates, obtained over a 10-year period from localized cutaneous,
      mucosal, and disseminated leishmaniasis patients, with randomly amplified
      polymorphic DNA (RAPD). Electrophoretic profiles were mostly unique across
      species. All typing protocols revealed polymorphism among the 45 CP L.
      braziliensis isolates, which displayed eight different RAPD patterns and greater
      than 80% overall fingerprint identity, attesting to the adequacy of the tools to
      assess strain variability in CP's geographically limited population of parasites.
      The dendrogram based on the sum of RAPD profiles of each isolate unveiled nine
      discrete typing units clustered into five clades. Global positioning showed
      extensive overlap of these clades in CP, precluding geographic sequestration as
      the mechanism of the observed structuralization. Finally, all forms of ATL
      presented a statistically significant difference in their frequencies among the
      clades, suggesting that L. braziliensis genotypes may be accompanied by specific
      disease manifestation after infection.

PMID- 14688131
TI  - Survival strategy of obligately intracellular Ehrlichia chaffeensis: novel
      modulation of immune response and host cell cycles.
AB  - Ehrlichia chaffeensis is an obligatory intracellular bacterium which resides in
      an early endosome in monocytes. E. chaffeensis infection in a human monocyte cell
      line (THP1) significantly altered the transcriptional levels of 4.5% of host
      genes, including those coding for apoptosis inhibitors, proteins regulating cell
      differentiation, signal transduction, proinflammatory cytokines, biosynthetic and
      metabolic proteins, and membrane trafficking proteins. The transcriptional
      profile of the host cell revealed key themes in the pathogenesis of Ehrlichia.
      First, E. chaffeensis avoided stimulation of or repressed the transcription of
      cytokines involved in the early innate immune response and cell-mediated immune
      response to intracellular microbes, such as the interleukin-12 (IL-12), IL-15,
      and IL-18 genes, which might make Ehrlichia a stealth organism for the
      macrophage. Second, E. chaffeensis up-regulated NF-kappaB and apoptosis
      inhibitors and differentially regulated cell cyclins and CDK expression, which
      may enhance host cell survival. Third, E. chaffeensis also inhibited the gene
      transcription of RAB5A, SNAP23, and STX16, which are involved in membrane
      trafficking. By comparing the transcriptional response of macrophages infected
      with other bacteria and that of macrophages infected with E. chaffeensis, we have
      identified few genes that are commonly induced and no commonly repressed genes.
      These results illustrate the stereotyped macrophage response to other pathogens,
      in contrast with the novel host response to obligate intracellular Ehrlichia,
      whose survival depends entirely on a long evolutionary process of outmaneuvering
      macrophages.

PMID- 14688133
TI  - Individual Mycobacterium tuberculosis resuscitation-promoting factor homologues
      are dispensable for growth in vitro and in vivo.
AB  - Mycobacterium tuberculosis possesses five genes with significant homology to the
      resuscitation-promoting factor (Rpf) of Micrococcus luteus. The M. luteus Rpf is
      a secreted approximately 16-kDa protein which restores active growth to cultures
      of M. luteus rendered dormant by prolonged incubation in stationary phase. More
      recently, the Rpf-like proteins of M. tuberculosis have been shown to stimulate
      the growth of extended-stationary-phase cultures of Mycobacterium bovis BCG.
      These data suggest that the Rpf proteins can influence the growth of
      mycobacteria; however, the studies do not demonstrate specific functions for the
      various members of this protein family, nor do they assess the function of M.
      tuberculosis Rpf homologues in vivo. To address these questions, we have
      disrupted each of the five rpf-like genes in M. tuberculosis Erdman, and analyzed
      the mutants for their growth in vitro and in vivo. In contrast to M. luteus, for
      which rpf is an essential gene, we find that all of the M. tuberculosis rpf
      deletion mutant strains are viable; in addition, all show growth kinetics similar
      to Erdman wild type both in vitro and in mouse organs following aerosol
      infection. Analysis of rpf expression in M. tuberculosis cultures from early log
      phase through late stationary phase indicates that expression of the rpf-like
      genes is growth phase-dependent, and that the expression patterns of the five M.
      tuberculosis rpf genes, while overlapping to various degrees, are not uniform. We
      also provide evidence that mycobacterial rpf genes are expressed in vivo in the
      lungs of mice acutely infected with virulent M. tuberculosis.

PMID- 14688134
TI  - Isolation and characterization of a secretory component of Echinococcus
      multilocularis metacestodes potentially involved in modulating the host-parasite
      interface.
AB  - Echinococcus multilocularis metacestodes are fluid-filled, vesicle-like
      organisms, which are characterized by continuous asexual proliferation via
      external budding of daughter vesicles, predominantly in the livers of infected
      individuals. Tumor-like growth eventually leads to the disease alveolar
      echinococcosis (AE). We employed the monoclonal antibody (MAb) E492/G1,
      previously shown to be directed against a carbohydrate-rich, immunomodulatory
      fraction of Echinococcus granulosus, to characterize potentially related
      components in E. multilocularis. Immunofluorescence studies demonstrated that MAb
      E492/G1-reactive epitopes were found predominantly on the laminated layer and in
      the periphery of developing brood capsules. The respective molecules were
      continuously released into the exterior medium and were also found in the
      parasite vesicle fluid. The MAb E492/G1-reactive fraction in E. multilocularis,
      named Em492 antigen, was isolated by immunoaffinity chromatography. Em492 antigen
      had a protein/carbohydrate ratio of 0.25, reacted with a series of lectins, and
      is related to the laminated layer-associated Em2(G11) antigen. The epitope
      recognized by MAb E492/G1 was sensitive to sodium periodate but was not affected
      by protease treatment. Anti-Em492 immunoglobulin G1 (IgG1) and IgG2 and, at lower
      levels, IgG3 were found in sera of mice suffering from experimentally induced
      secondary, but not primary, AE. However, with regard to cellular immunity, a
      suppressive effect on concanavalin A- or crude parasite extract-induced
      splenocyte proliferation in these mice was observed upon addition of Em492
      antigen, but trypan blue exclusion tests and transmission electron microscopy
      failed to reveal any cytotoxic effect in Em492 antigen-treated spleen cells. This
      indicated that Em492 antigen could be modulating the periparasitic cellular
      environment during E. multilocularis infection through as yet unidentified
      mechanisms and could be one of the factors contributing to immunosuppressive
      events that occur at the host-parasite interface.

PMID- 14688135
TI  - Helicobacter pylori disrupts STAT1-mediated gamma interferon-induced signal
      transduction in epithelial cells.
AB  - Infection with Helicobacter pylori is chronic despite a vigorous mucosal immune
      response characterized by gastric T-helper type 1 cell expansion and gamma
      interferon (IFN-gamma) production. IFN-gamma signals by activation and nuclear
      translocation of signal transducer and activator of transcription 1 (STAT1);
      however, the effect of H. pylori infection on IFN-gamma-STAT1 signaling is
      unknown. We infected human gastric (MKN45 and AGS) and laryngeal (HEp-2)
      epithelial cell lines with type 1 and type 2 H. pylori strains and then
      stimulated them with IFN-gamma. Western blotting of whole-cell protein extracts
      revealed that infection with live, but not heat-killed, H. pylori time
      dependently decreased IFN-gamma-induced STAT1 tyrosine phosphorylation.
      Electrophoretic mobility shift assay of nuclear protein extracts demonstrated
      that H. pylori infection reduced IFN-gamma-induced STAT1 DNA binding. STAT1 was
      unable to translocate from the cytoplasm to the nucleus in H. pylori-infected HEp
      2 cells examined by immunofluorescence, and reverse transcription-PCR showed that
      IFN-gamma-induced interferon regulatory factor 1 expression was inhibited. These
      effects were independent of the cagA, cagE, and VacA status of the infecting H.
      pylori strain. Furthermore, neither H. pylori culture supernatants nor
      conditioned medium from H. pylori-infected MKN45 cells inhibited IFN-gamma
      induced STAT1 tyrosine phosphorylation, suggesting that inhibition is independent
      of a soluble epithelial or bacterial factor but is dependent on bacterial contact
      with epithelial cells. H. pylori disruption of IFN-gamma-STAT1 signaling in
      epithelial cells may represent a mechanism by which the bacterium modifies
      mucosal immune responses to promote its survival in the human host.

PMID- 14688137
TI  - Development, characterization, and functional activity of a panel of specific
      monoclonal antibodies to inner core lipopolysaccharide epitopes in Neisseria
      meningitidis.
AB  - A panel of six murine monoclonal antibodies (MAbs) recognizing inner core
      lipopolysaccharide (LPS) epitopes of Neisseria meningitidis was prepared and
      characterized in order to determine the diversity of inner core LPS glycoforms
      among disease and carrier isolates. Two of these MAbs, L2-16 (immunoglobulin G2b
      [IgG2b]) and LPT3-1 (IgG2a), together with a third, previously described MAb,
      L3B5 (IgG3), showed reactivity, either individually or in combination, with all
      except 3 of 143 disease and carriage isolates (125 of 126 strains from blood,
      cerebrospinal fluid, or skin biopsy samples and 15 of 17 from nasopharyngeal
      cultures). MAbs L3B5, L2-16, and LPT3-1 were further characterized in an indirect
      immunofluorescence assay. All three MAbs bound to the bacterial cell surface,
      findings that correlated strongly with whole-cell enzyme-linked immunosorbent
      assay and immunodot blots. However, in contrast to our findings with L3B5, cell
      surface binding of L2-16 or LPT 3-1 did not correlate with functional activity as
      determined by bactericidal or infant rat passive protection assays against wild
      type N. meningitidis strains. These findings are provocative with respect to the
      requirements for protective activity of antibodies and the development of inner
      core LPS vaccines against invasive meningococcal disease.

PMID- 14688136
TI  - The ADP ribosyltransferase domain of Pseudomonas aeruginosa ExoT contributes to
      its biological activities.
AB  - ExoT is a type III secreted effector protein found in almost all strains of
      Pseudomonas aeruginosa and is required for full virulence in an animal model of
      acute pneumonia. It is comprised of an N-terminal domain with GTPase activating
      protein (GAP) activity towards Rho family GTPases and a C-terminal ADP
      ribosyltransferase (ADPRT) domain with minimal activity towards a synthetic
      substrate in vitro. Consistent with its activity as a Rho family GTPase, ExoT has
      been shown to inhibit P. aeruginosa internalization into epithelial cells and
      macrophages, disrupt the actin cytoskeleton through a Rho-dependent pathway, and
      inhibit wound repair in a scrape model of injured epithelium. We have previously
      shown that mutation of the invariant arginine of the GAP domain to lysine (R149K)
      results in complete loss of GAP activity in vitro but only partially inhibits
      ExoT anti-internalization and cell rounding activity. We have constructed in
      frame deletions and point mutations within the ADPRT domain in order to test
      whether this domain might account for the residual activity observed in ExoT GAP
      mutants. Deletion of a majority of the ADPRT domain (residues 234 to 438) or
      point mutations of the ADPRT catalytic site (residues 383 to 385) led to distinct
      changes in host cell morphology and substantially reduced the ability of ExoT to
      inhibit in vitro epithelial wound healing over a 24-h period. In contrast, only
      subtle effects on the efficiency of ExoT-induced bacterial internalization were
      observed in the ADPRT mutant forms. Expression of each domain individually in
      Saccharomyces cerevisiae was toxic, whereas expression of each of the
      catalytically inactive mutant domains was not. Collectively, these data
      demonstrate that the ADPRT domain of ExoT is active in vivo and contributes to
      the pathogenesis of P. aeruginosa infections.

PMID- 14688138
TI  - Stable T-cell population expressing an effector cell surface phenotype in the
      lungs of mice chronically infected with Mycobacterium tuberculosis.
AB  - Analysis of T-cell subsets accumulating in the lungs of C57BL/6 mice chronically
      infected with Mycobacterium tuberculosis revealed that both CD4 and CD8 T-cell
      populations expressed a cell surface phenotype consistent with that of effector T
      cells and that a significant proportion of these cells were in the process of
      secreting gamma interferon.

PMID- 14688139
TI  - In vitro induction of Neospora caninum bradyzoites in vero cells reveals
      differential antigen expression, localization, and host-cell recognition of
      tachyzoites and bradyzoites.
AB  - We report on an optimized method for the in vitro culture of tissue cyst-forming
      Neospora caninum bradyzoites in Vero cells and the separation of viable parasites
      from host cells. Treatment of tachyzoite-infected Vero cell cultures with 17
      microM sodium nitroprusside for 8 days severely scaled down parasite
      proliferation, led to reduced expression of tachyzoite surface antigens, and
      induced the expression of the bradyzoite marker NcBAG1 and the cyst wall antigen
      recognized by the monoclonal antibody MAbCC2. Transmission electron microscopy
      demonstrated that intracellular parasites were located within parasitophorous
      vacuoles that were surrounded by a cyst wall-like structure, and the dense
      granule antigens NcGRA1, NcGRA2, and NcGRA7 were incorporated into the cyst wall.
      Adhesion-invasion assays employing purified tachyzoites and bradyzoites showed
      that tachyzoites adhered to, and invaded, Vero cells with higher efficiency than
      bradyzoites. However, removal of terminal sialic acid residues from either the
      host cell or the parasite surface increased the invasion of Vero cells by
      bradyzoites, but not tachyzoites.

PMID- 14688140
TI  - Effect of CpG oligodeoxynucleotides on the immunogenicity of Pfs25, a Plasmodium
      falciparum transmission-blocking vaccine antigen.
AB  - Antibodies directed against Pfs25, a protein present on the surface of zygotes
      and ookinetes of Plasmodium falciparum, completely block pathogen transmission.
      We evaluated the immunomodulatory effect of CpG oligodeoxynucleotides (ODN) on
      the immunogenicity of recombinant Pfs25 (rPfs25) formulated in alum (Al).
      Immunization of mice with rPfs25 plus CpG ODN improved both the antibody titer (a
      30-fold-higher antibody response than that with rPfs25-Al alone) and avidity.
      Coadministration of CpG ODN dramatically enhanced the titer of immunoglobulin G2A
      (IgG2a) compared to the titer of the IgG1-dominant response caused by rPfs25-Al
      alone, and the sera from the CpG ODN-coadministered group completely blocked the
      transmission of P. falciparum parasites to mosquitoes, as determined by membrane
      feeding assays. However, transmission-blocking experiments revealed that blocking
      efficacy was dependent on high-titer antibody levels, independent of isotypes.
      These results suggest that CpG ODN can be used as an adjuvant to enhance the
      immunogenicity of rPfs25 as a malaria transmission-blocking vaccine.

PMID- 14688141
TI  - Inhibition of CD1 expression in human dendritic cells during intracellular
      infection with Leishmania donovani.
AB  - Dendritic cells can initiate antimicrobial responses by CD1-mediated presentation
      of pathogen-derived glycolipids. We show that the protozoan Leishmania donovani
      inhibits CD1 expression and prevents activation of CD1-restricted T cells by
      dendritic cells. Evasion of presentation by CD1 may represent a Leishmania
      survival strategy to avoid recognition of abundant parasite glycolipids.

PMID- 14688142
TI  - Autotransporter genes pic and tsh are associated with Escherichia coli strains
      that cause acute pyelonephritis and are expressed during urinary tract infection.
AB  - We have identified two chromosomal open reading frames in uropathogenic
      Escherichia coli (UPEC) strain CFT073 which are highly homologous to serine
      protease autotransporters Pic and Tsh. Both cloned determinants were correlated
      with the presence of 105- to 110-kDa proteins in the culture supernatants.
      Furthermore, in cellular fractionation experiments, 30-kDa polypeptides were
      identified in the outer membrane; we speculated that these proteins are the beta
      barrel portions of the autotransporter homologues. Furthermore, Pic-containing
      culture supernatants have serine protease activity. In reverse transcription-PCR
      analyses, the expression of the pic and tsh genes in E. coli CFT073 was higher in
      broth cultures grown at 37 degrees C than at 25 degrees C. Moreover, pic and tsh
      were expressed by bacteria isolated from urine of transurethrally infected mice.
      The tsh determinant was identified in 63% of our clinical UPEC strain isolates (n
      = 87) and in 33% of fecal strains (n = 27), whereas pic was present in 31% of the
      pyelonephritis (n = 67) and 7% of the fecal strains. There was no significant
      correlation between cystitis strains (n = 20) and the pic determinant.

PMID- 14688143
TI  - Relationship between Candida albicans virulence during experimental
      hematogenously disseminated infection and endothelial cell damage in vitro.
AB  - Candida albicans must penetrate the endothelial cell lining of the vasculature to
      invade the deep tissues during a hematogenously disseminated infection. We
      compared 27 C. albicans mutants with their wild-type parent for their capacity to
      damage endothelial cells in vitro and cause a lethal infection in mice following
      tail vein inoculation. Of 10 mutants with significantly impaired capacity to
      damage endothelial cells, all had attenuated virulence. Therefore, the
      endothelial cell damage assay can be used as a screen to identify some virulence
      factors relevant to hematogenously disseminated candidiasis.

PMID- 14688144
TI  - Protection against anthrax toxemia by hexa-D-arginine in vitro and in vivo.
AB  - The anthrax toxin protective antigen precursor is activated by proteolytic
      cleavage by furin or a furin-like protease. We present here data demonstrating
      that the small stable furin inhibitor hexa-D-arginine amide delays anthrax toxin
      induced toxemia both in cells and in live animals, suggesting that furin
      inhibition may represent a reasonable avenue for therapeutic intervention in
      anthrax.

PMID- 14688145
TI  - Acquisition of host plasmin activity by the Swine pathogen Streptococcus suis
      serotype 2.
AB  - In this study, the plasminogen-binding activity of Streptococcus suis serotype 2
      was investigated. Bound human plasminogen was activated by purified
      streptokinase, urokinase, or Streptococcus dysgalactiae subsp. equisimilis
      culture supernatant. Both human and porcine plasminogen were bound by S. suis.
      Binding was inhibited by epsilon-aminocaproic acid, and the plasminogen receptor
      was heat and sodium dodecyl sulfate resistant. One of the receptors was
      identified as glyceraldehyde-3-phosphate dehydrogenase. S. suis-associated
      plasmin activity was capable of activating free plasminogen, which in turn could
      contribute to degradation of fibronectin. This is the first report on the
      plasminogen-binding activity of S. suis. Further studies may reveal a
      contribution of this activity to the virulence of S. suis.

PMID- 14688146
TI  - Activation of Serratia marcescens hemolysin through a conformational change.
AB  - For Serratia marcescens, secreted hemolysin/cytotoxin is not only secreted but
      also activated by an outer membrane protein. Excluding posttranslational
      processing by mass spectrometry, the conformation of active and inactive ShlA
      derivatives strongly differed in electrophoretic mobilities, gel permeation
      chromatography, sensitivity to trypsin, circular dichroism, and intrinsic
      fluorescence. We concluded that ShlB interacts with ShlA during secretion and
      imposes a conformational change in ShlA to form the active hemolysin.

PMID- 14688147
TI  - Antibody-mediated neutralization of pertussis toxin-induced mitogenicity of human
      peripheral blood mononuclear cells.
AB  - Antibody-mediated neutralization of pertussis toxin-induced proliferation of
      human peripheral blood mononuclear cells (PBMC) was assessed using alamarBlue and
      compared with results from the Chinese hamster ovary (CHO) cell assay using sera
      from vaccinated adults and convalescent children. Neutralization values for the
      CHO assay were similar for vaccinated and convalescent subjects; however. the
      convalescent group had higher titers in the PBMC assay. Results for pertussis
      toxin neutralization with the CHO assay appear to be distinct from those with the
      PBMC assay.

PMID- 14688149
TI  - What is the most relevant standard of success in assisted reproduction? The
      singleton, term gestation, live birth rate per cycle initiated: the BESST
      endpoint for assisted reproduction.
AB  - Assisted reproduction programmes do not report success consistently. Rates vary
      with the definition used. Success must reflect delivery of healthy babies, and
      the burden of treatment to couples. We report the singleton, term gestation, live
      birth rate of a baby per assisted reproductive technology cycle initiated for a
      large IVF programme. We defined assisted reproductive technology cycles as those
      initiated with the intention of oocyte collection. We examined cycles conducted
      through Monash IVF in 2001. All women with positive pregnancy tests had first
      trimester ultrasonography. Obstetric outcomes were recorded. All babies had
      neonatal examinations conducted by paediatricians. A total of 644 positive
      pregnancy tests were recorded in 2600 cycles; 509 showed fetal heart motion. Of
      448 deliveries, 328 were singleton and 120 were multiple. There were 290
      singleton deliveries at term gestation. In 2001, a couple had an 11.1% chance of
      delivering a singleton, term gestation, live baby per assisted reproductive
      technology cycle begun. We suggest that delivery of a single, term gestation,
      live baby per cycle initiated is the most relevant standard of success. This
      statistic was 11.1% at Monash IVF. We encourage programmes to report this BESST
      (Birth Emphasizing a Successful Singleton at Term) outcome.

PMID- 14688150
TI  - Hormone replacement therapy and acute coronary outcomes: methodological issues
      between randomized and observational studies.
AB  - A large number of observational studies, supported by animal and basic research
      studies, have shown a protective effect of hormone replacement therapy (HRT) on
      acute coronary outcomes. The recent large randomized Women's Health Initiative
      (WHI) study reported the opposite result, i.e. a small risk increase of 29% for
      acute coronary outcomes under estrogen-progestin treatment. Possible
      methodological reasons for these discrepancies are discussed. Despite
      randomization, the reported small increase in risk in the WHI study could be
      spurious because of differential unblinding of HRT users, which could have
      resulted in higher detection rates of otherwise clinically unrecognized acute
      myocardial infarction in these women. We show that altering diagnostic patterns
      because of unblinding could lower the crude rate ratio of 1.28 to 1.02. In the
      observational studies, the protective effect may have been exaggerated due to a
      healthy user bias and to the inappropriate choice of the reference group. Using
      an alternative reference group, the combined rate ratio of 0.67 was increased to
      0.82. The diametrical effects of HRT on acute coronary outcomes found between the
      observational studies and the WHI Study may be a result not only of bias in the
      observational studies, but also of bias in the WHI Study.

PMID- 14688151
TI  - Ovarian tissue banking for cancer patients: is ovarian cortex cryopreservation
      presently justified?
AB  - The effect of chemotherapy and radiotherapy on future fertility is of concern to
      patients and their families. Whereas sperm banking is commonly performed, female
      gametes are not so amenable to cryopreservation. One alternative includes
      postponing cancer treatment to enable ovulation induction and oocyte aspiration.
      Whenever possible, retrieved oocytes should be fertilized in vitro prior to
      cryopreservation. Frozen embryos could serve to produce pregnancies if ovarian
      failure occurs. Donor sperm can be offered to single patients, as frozen-thawed
      unfertilized oocytes yield poor pregnancy rates. Ovarian cortex cryopreservation
      should still be considered an experimental technology as no pregnancies have been
      obtained in humans. Therefore, ovarian cortex banking should be used only for
      young girls, adolescents and when IVF is contraindicated. Reattachment of ovarian
      vasculature could prevent ischaemic follicular loss and enable ovarian
      transplantation in the future. This procedure is currently under investigation in
      animals. At the present time, we recommend urgent IVF in most patients requesting
      fertility preservation. Ovarian cryopreservation should be offered when emergency
      IVF is not possible.

PMID- 14688152
TI  - Menstrual effluent induces epithelial-mesenchymal transitions in mesothelial
      cells.
AB  - BACKGROUND: Menstrual effluent affects mesothelial cell (MC) morphology. We
      evaluated whether these changes were consistent with epithelial-mesenchymal
      transitions (EMT). METHODS: Monolayer cultures of MC were incubated overnight in
      conditioned media, prepared from cells isolated form menstrual effluent, with or
      without kinase and ATP inhibitors. Changes in cell morphology were monitored
      using time-lapse video microscopy and immunohistochemistry. Effects on the
      expression of EMT-associated molecules were evaluated using real-time RT-PCR
      and/or Western blot analysis. RESULTS: Incubation in conditioned media disrupted
      cell-cell contacts, and increased MC motility. The changes were reversible.
      During the changes the distribution of cytokeratins, fibrillar actin and alpha
      tubulin changed. Sodium azide, an inhibitor of ATP production, and Genistein, a
      general tyrosine kinase inhibitor, antagonized these effects. Wortmannin, a
      phosphatidylinositol 3-kinase inhibitor, and SU6656, an Src tyrosine kinase
      inhibitor, only partially antagonized the effect. The expression of Snail and
      vimentin was markedly up-regulated, whereas the expression of E-cadherin was
      decreased and cytokeratins were altered. CONCLUSIONS: In MC, menstrual effluent
      initiates a reversible, energy-dependent transition process from an epithelial to
      a mesenchymal phenotype. Involvement of the (Src) tyrosine kinase signalling
      pathway and the changes in the expression of cytokeratins, Snail, vimentin and E
      cadherin demonstrate that the morphological changes are EMT.

PMID- 14688153
TI  - Expression of nitric oxide synthase and effect of substrate manipulation of the
      nitric oxide pathway in mouse ovarian follicles.
AB  - BACKGROUND: Nitric oxide (NO) is a cell messenger with multiple actions in
      different biological systems, implicated in the control of follicle and oocyte
      function. NO is formed from L-arginine by isoforms of nitric oxide synthase (NOS)
      via NG-hydroxy-L-arginine, with L-citrulline as a byproduct. This study aimed to
      show how modulation of NO by manipulating NOS substrates would affect mouse
      follicle growth and ovulation in vitro, where vascular effects of NO are
      attenuated. METHODS: Immunohistochemistry [endothelial (eNOS) and inducible
      (iNOS)] and in situ hybridization (iNOS) were applied on mouse ovaries. Cultured
      follicles were also stained for iNOS by immunohistochemistry. For follicles
      cultured in the presence or absence of L-arginine, the ability of L-citrulline or
      NG-hydroxy-L-arginine to substitute for L-arginine was assessed in terms of
      follicle growth and ovulation. RESULTS: iNOS and eNOS were localized in oocytes
      and theca, with some staining in granulosa. iNOS mRNA occurred predominantly in
      granulosa and oocyte. Omission of L-arginine significantly reduced follicle
      survival and ovulation. Partial compensation for L-arginine withdrawal was
      achieved with L-citrulline and NG-hydroxy-L- arginine. Specific abnormalities of
      follicle growth were noted. CONCLUSIONS: NOS is present in mouse follicles, and
      its action is necessary at a local level for normal follicle development in
      vitro. Reduced growth, persistent basement membranes and reduced ovulation were
      associated with in vitro disruption of NO.

PMID- 14688154
TI  - Revised 2003 consensus on diagnostic criteria and long-term health risks related
      to polycystic ovary syndrome (PCOS).
AB  - Since the 1990 NIH-sponsored conference on polycystic ovary syndrome (PCOS), it
      has become appreciated that the syndrome encompasses a broader spectrum of signs
      and symptoms of ovarian dysfunction than those defined by the original diagnostic
      criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome
      of ovarian dysfunction along with the cardinal features hyperandrogenism and
      polycystic ovary (PCO) morphology. PCOS remains a syndrome and, as such, no
      single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for
      clinical diagnosis. Its clinical manifestations may include: menstrual
      irregularities, signs of androgen excess, and obesity. Insulin resistance and
      elevated serum LH levels are also common features in PCOS. PCOS is associated
      with an increased risk of type 2 diabetes and cardiovascular events.

PMID- 14688155
TI  - Serum and adipocyte resistin in polycystic ovary syndrome with insulin
      resistance.
AB  - BACKGROUND: The aim of this study was to investigate the relationship between
      resistin and insulin resistance in patients with polycystic ovary syndrome
      (PCOS). METHODS: We compared serum resistin levels in 17 PCOS women and 10 lean,
      healthy, age-matched non-PCOS women and also compared levels of insulin receptor
      (IR), phosphatidylinositol-3 kinase (PI3-kinase), glucose transporter 4 (GLUT4)
      protein and resistin mRNA in adipocytes isolated from the omental adipose tissue
      of five of the PCOS patients and five age- and weight-matched, non-PCOS controls,
      to look for local defects in insulin action in PCOS. RESULTS: The PCOS group was
      hyperinsulinaemic and displayed an impaired insulin response in a 75 g oral
      glucose tolerance test and an abnormal homeostasis model insulin resistance
      index. Serum resistin levels were similar in PCOS patients and controls; however,
      resistin mRNA levels were 2-fold higher in adipocytes from PCOS patients. No
      correlation was found between serum resistin levels and either the BMI or
      testosterone levels. Western blot analysis showed that adipocyte levels of
      insulin receptor, PI3-kinase, and GLUT4 were respectively decreased by 56, 39.4
      and 54% in PCOS patients compared with controls. CONCLUSIONS: These results
      suggest that overexpression of the resistin gene in adipocytes may be a local
      determinant factor in the pathogenesis of PCOS.

PMID- 14688156
TI  - GnRH antagonists and mild ovarian stimulation for intrauterine insemination: a
      randomized study comparing different gonadotrophin dosages.
AB  - BACKGROUND: The precise role of GnRH antagonists in the armamentarium of drugs
      for stimulation of ovulation associated with intrauterine insemination remains to
      be clarified. In this study, we have compared two different protocols employing
      GnRH antagonists in order to determine the lower effective dose of gonadotrophins
      to use. METHODS: Sixty-six couples with unexplained infertility or moderate male
      subfertility were recruited. Starting on day 3 of the cycle, 32 patients were
      randomized to receive 50 IU of recombinant FSH per day, whereas 34 were treated
      with 50 IU of recombinant FSH on alternate days. Women received the GnRH
      antagonist Ganirelix at a dose of 0.25 mg per day starting on the day in which a
      leading follicle > or =14 mm in mean diameter was visualized, until HCG
      administration. Insemination was performed 34 h after HCG injection. RESULTS: The
      regimen with daily recombinant FSH was associated with a lower rate of mono
      ovulation (53.3% versus 78.8%, P=0.06) but also with a higher clinical pregnancy
      rate per initiated cycle (34.4% versus 5.9%, P=0.005). CONCLUSIONS: A protocol of
      recombinant FSH 50 IU daily and GnRH antagonist may represent an effective and
      safe regimen for ovulation induction associated with intrauterine insemination.

PMID- 14688157
TI  - Effects of vitamin D and estrogen receptor gene polymorphisms on the changes in
      lumbar bone mineral density with multiple pregnancies in Japanese women.
AB  - BACKGROUND: Our aims were to follow the longitudinal changes in lumbar spine bone
      mineral density (BMD) with multiple pregnancies, and to study whether
      polymorphisms in the vitamin D receptor (VDR) and estrogen receptor (ER) genes
      may influence the results. METHODS: We repeatedly measured the BMD of the lumbar
      spine (L2-L4) of 133 women who had undergone two successive pregnancies and 73
      non-pregnant controls, and analysed the restriction fragment length polymorphisms
      using restriction endonucleases TaqI, ApaI and FokI for the VDR gene, and PvuII
      and XbaI for the ER gene. RESULTS: Cases and controls had no significant
      differences in the longitudinal BMD changes. The mean percentage change in lumbar
      BMD (DeltaBMD%) of the women with the XX/Xx genotype was significantly lower than
      that of the women with the xx genotype after adjusting for age at each delivery,
      BMD of the first scan, and interval between the scans (0.2 +/- 3.3 versus 2.0 +/-
      4.2%; P=0.030, analysis of covariance). Multiple regression analyses to evaluate
      the contribution of the XbaI polymorphism of the ER gene on DeltaBMD% showed that
      the percentage decrease in BMD was greater for women lacking the XbaI restriction
      site (adjusted R2=0.188, P<0.0001). CONCLUSIONS: The present study suggests that
      the DeltaBMD% was significantly influenced by the XbaI polymorphism of the ER
      gene.

PMID- 14688158
TI  - Frequent polymorphism of the mitochondrial DNA polymerase gamma gene (POLG) in
      patients with normal spermiograms and unexplained subfertility.
AB  - BACKGROUND: Male fertility largely depends on the quality of sperm production,
      which may be affected by environmental and genetic factors. In this study, we
      explored a possible role of the polymerase gamma (POLG) gene polymorphism,
      recently reported to be associated with male infertility in some populations.
      METHODS: The polymorphic CAG repeat (usually 10 codons long) in the POLG gene was
      studied in 1298 male subjects: 429 patients with infertility/subfertility, and
      869 controls (495 men from the general population with unknown fertility and 374
      recent fathers). In all subjects, the POLG polymorphism was assessed in relation
      to their semen quality, and--in the fertile controls--with biological fecundity
      measured as waiting time-to-pregnancy (TTP) for the couples. In the patients
      lacking the common POLG allele, the outcome of the assisted reproductive
      techniques (ART) for the couples was evaluated. RESULTS: The absence of one (10/
      not equal to 10) or both common POLG alleles (not equal to 10/not equal to 10)
      was more frequent among the subfertile patients than among fertile controls
      (P=0.021 and P=0.04 respectively). The estimated predictive value for infertility
      in a man homozygous for the POLG polymorphism was 15.5% (95% CI: 4.8-51%). There
      was a positive association with sperm concentration: 14.3% of the normospermic
      subfertile patients were homozygous for the absence of the common POLG allele
      (not equal to 10/not equal to 10), in comparison with 2.3% of unselected controls
      (P=0.001) and 0.9% of the fertile men (P=0.0001). No association with sperm
      motility, morphology and TTP was found. Spermatozoa of the three not equal to
      10/not equal to 10 patients treated with IVF retained the ability to penetrate
      the egg, but the fertilization rate was low. Nine homozygous not equal to 10/ not
      equal to 10 patients were treated with ICSI, resulting in pregnancy in seven
      couples. CONCLUSIONS: The POLG gene polymorphism should be considered as a
      possible contributing factor in patients with unexplained subfertility and normal
      spermiograms. The oocyte penetration ability of sperm may be partially impaired
      in the not equal to 10/not equal to 10 patients but most of them can be
      successfully treated with ICSI.

PMID- 14688159
TI  - Familial clustering of impaired spermatogenesis: no evidence for a common genetic
      inheritance pattern.
AB  - BACKGROUND: The aetiology of impaired spermatogenesis is unknown in the majority
      of cases. Evidence of a contribution of genetic factors is still scarce.
      Therefore, the aim of our study was to assess whether male factor subfertility
      due to impaired spermatogenesis has a familial component and to test different
      genetic models of inheritance. METHODS: Cases were all men with severe idiopathic
      impaired spermatogenesis attending our fertility clinic from January 1998 until
      December 2001. Controls were all men with normozoospermia attending our fertility
      clinic in the same period. Family data were collected from the medical records
      and by additional interviews of the probands. If subfertility of a first-degree
      relative was mentioned, permission was sought to contact the affected family
      member in order to obtain all medical information available, including the
      results of semen analyses. RESULTS: In total, 160 patients and 285 controls were
      included in the analysis. Family size and number of brothers and sisters were
      equally distributed in both groups. In the patient group, 1.63% of the brothers
      who had tried to father a child were mentioned to be subfertile compared to 5.8%
      in the control group [odds ratio 3.18 (95% confidence interval 1.59-6.37)]. The
      subfertility among the brothers in the patient group was more often due to
      reduced semen parameters compared to the control group. The data did not fit with
      frequent autosomal dominant or recessive segregation. CONCLUSION: Male factor
      subfertility due to impaired spermatogenesis appears to cluster in families. Our
      data suggests that heritable genetic factors play a role in a limited number of
      cases. Impaired spermatogenesis is not caused by a common genetic defect, but is
      most likely a complex disease in which several different factors play a role.

PMID- 14688160
TI  - Comparison between the sublingual and oral route of misoprostol for pre-abortion
      cervical priming in first trimester abortions.
AB  - BACKGROUND: Misoprostol has been used for achieving cervical priming before
      suction evacuation (SE) by the oral or vaginal route, although both routes have
      their shortcomings. We evaluated the efficacy of the sublingual versus oral route
      of misoprostol for cervical priming before SE. METHODS: A prospective clinical
      trial was carried out in 100 women with a period of gestation of between 6 and 12
      weeks who were sequentially allocated to two groups of 50 each. Both groups
      received 400 microg of misoprostol 3 h prior to SE by either the sublingual or
      the oral route. RESULTS: Demographically, both groups were similar. For all
      periods of gestation, sublingual misoprostol significantly improved cervical
      dilation (P<0.001) with a reduction in duration of surgery (P=0.024) compared
      with the oral route. Mean (+/- SD) pain scores for the sublingual and oral groups
      were similar (2.6 +/- 1.4 versus 3.5 +/- 1.1). No major complications occurred in
      either of the two groups. CONCLUSION: the sublingual route is an effective
      alternative to oral administration of misoprostol for cervical dilation. To the
      best of our knowledge, this is the first study to compare the efficacy of the
      sublingual versus the oral route of misoprostol for cervical priming before SE.

PMID- 14688161
TI  - Effects of misoprostol on uterine contractility following different routes of
      administration.
AB  - BACKGROUND: The effect of misoprostol administered by different routes on
      pregnant uterine contractility was investigated. METHODS: Thirty-two women with a
      pregnancy between 8 and 11 weeks of gestation requesting termination of pregnancy
      were recruited. Misoprostol was administered either orally (0.4 mg), vaginally
      (0.4 mg) or sublingually (0.2 or 0.4 mg) according to consecutive allocation.
      Intrauterine pressure was recorded using a Grass polygraph connected to a
      pressure transducer 30 min before misoprostol was given and for 4 h thereafter.
      At the end of the recording, suction curettage was performed. RESULTS: The first
      effect observed was an increase in uterine tonus, which occurred after a
      significantly shorter time following oral (7.8 min) and sublingual (10.7-11.5
      min) than after vaginal (19.4 min) treatment. The time to maximum tonus elevation
      was also significantly shorter (39.5, 47.1-51.7 and 62.2 min for the three groups
      respectively). Regular uterine contractions developed in all subjects following
      sublingual and vaginal administration but not after oral administration. The
      increase in uterine activity measured in Montevideo Units was significantly
      higher after 2 h and thereafter for sublingual and vaginal treatment than for
      oral misoprostol. CONCLUSIONS: Based on recording of uterine activity, sublingual
      misoprostol acts as rapidly as oral treatment, while development of contractions
      was similar to that seen following vaginal administration.

PMID- 14688162
TI  - Prediction of late failure after medical abortion from serial beta-hCG
      measurements and ultrasonography.
AB  - BACKGROUND: Surgical treatment of failed medical abortion may be performed
      several weeks after initiation of the abortion. There are no recognized methods
      for early identification of these late failures. We assessed the prognostic
      values of beta-hCG and ultrasonography in predicting late failure after medical
      abortion. METHODS: A total of 694 consecutive women with gestational age (GA) <63
      days were followed up with beta-hCG measurements initially on the day of
      treatment and on day 8 and day 15, after the medically induced abortion with
      mifepristone and gemeprost. Measurement of the endometrial thickness by
      ultrasonography was performed on day 15 after induction of medical abortion.
      Failures diagnosed after day 15 and within 15 weeks were identified and
      classified as late failures. All interventions in this group were due to bleeding
      problems. The predictive values of different absolute and relative beta-hCG
      levels and different endometrial thickness were analysed. RESULTS: Of all
      failures in the study period, 65% (32) were diagnosed after the 2 week follow-up,
      and categorized as late failures. The absolute and the relative beta-hCG values
      on days 8 and 15 as well as the endometrial thickness on day 15 were greater
      among late failures than successes. Used as a predictive test, the positive
      predictive values of these variables were low. CONCLUSION: Neither beta-hCG nor
      endometrial thickness can be used clinically as diagnostic tests in predicting
      late failure after medical abortion.

PMID- 14688163
TI  - A randomized, double-blind, multicentre clinical trial comparing starting doses
      of 150 and 200 IU of recombinant FSH in women treated with the GnRH antagonist
      ganirelix for assisted reproduction.
AB  - BACKGROUND: Studies with the GnRH antagonist ganirelix in assisted reproduction
      have indicated that compared with traditional GnRH agonist downregulation
      protocols, slightly fewer oocytes are retrieved. In this study it was
      investigated whether an increase in the starting dose of recombinant FSH (rFSH)
      could compensate for this loss. METHODS: A randomized, double-blind, multicentre
      clinical trial comparing a starting dose of 150 and 200 IU of rFSH (follitropin
      beta), in women undergoing treatment with the GnRH antagonist ganirelix. RESULTS:
      In total, 257 women were treated with rFSH, of whom 131 received 150 IU and 126
      women 200 IU. Overall, 10.3 oocytes were retrieved in the 150 IU group and 11.9
      in the 200 IU group (P=0.051). This difference became significant when women with
      cycle cancellation before HCG administration were excluded. Nearly 500 IU of
      additional rFSH was given in the high-dose group (2014 versus 1541 IU). In the
      low-dose group, 4.6 high-quality embryos were obtained compared with 4.5 in the
      high-dose group. Vital pregnancy rates were similar (31 and 25% in the 150 and
      200 IU-treated women, respectively). Serum concentrations of FSH, estradiol and
      progesterone were significantly higher in the high-dose group at day 6 of rFSH
      treatment and on the day of HCG administration. In the high-dose group, serum LH
      concentrations were higher at day 6 of rFSH treatment but lower at the day of HCG
      administration. CONCLUSION: By increasing the starting dose from 150 to 200 IU of
      rFSH, slightly more oocytes can be retrieved in GnRH antagonist protocols for
      assisted reproduction. However, because this did not translate into a higher
      number of high quality embryos, the clinical relevance of such a dose increase
      may be questioned.

PMID- 14688164
TI  - Differences in time to natural conception between women with unexplained
      infertility and infertile women with minor endometriosis.
AB  - BACKGROUND: Opinion remains divided as to whether finding endometriotic lesions
      in the absence of adhesions has an adverse effect on the likelihood of
      conception. METHODS: This was a retrospective study of 192 fully investigated
      infertile couples, followed up for up to 3 years following laparoscopy. Women
      studied were ovulating, <40 old years and their partners had normal sperm
      parameters. All 117 women with unexplained infertility and 75 with minimal/mild
      endometriosis without adhesive disease were managed conservatively. RESULTS:
      Women with endometriosis were found to have a lower probability of pregnancy
      compared with women with unexplained infertility (36% versus 55%; P<0.05). Other
      factors adversely associated with pregnancy were primary infertility, smoking and
      longer duration (>3 years) of infertility. However, the effects of duration of
      infertility and primary infertility were not observed to be statistically
      significant for women with endometriosis. CONCLUSIONS: The findings, although
      undertaken in a select population undergoing laparoscopy, suggest the likelihood
      of pregnancy is reduced in infertile women with minimal/mild endometriosis
      compared with those infertile women with a normal pelvis. Duration of infertility
      and a previous history of pregnancy are important in predicting the likelihood of
      pregnancy in women with no obvious cause for their infertility (unexplained),
      whilst the relationship may be more complex in women with minor endometriosis

PMID- 14688165
TI  - The levels of C-reactive protein in women treated by IVF.
AB  - BACKGROUND: The complex regulation of endometrial receptivity and embryo
      implantation involves cytokines, several of which are stimulators of the acute
      phase reactant C-reactive protein (CRP). The purpose of this study was to
      evaluate the concentrations of serum CRP in women treated by IVF. METHODS:
      Seventy-two women who underwent IVF treatment were prospectively studied. The
      levels of serum CRP were evaluated on the following days: oocyte retrieval,
      embryo transfer, 5, 6 or 7 days afterwards and 12 days after embryo transfer.
      RESULTS: CRP levels increased from 6.8 +/- 9.5 mg/l on oocyte retrieval day to
      14.6 +/- 12.5 mg/l on days 5-7 post-transfer (P<0.0001). The ratios of CRP levels
      for transfer day/pick-up day were 1.2 in women who conceived versus 2.5 in the
      non-pregnant group (P=0.01). CONCLUSION: In women treated by IVF the
      concentrations of CRP in blood increase significantly during the first week
      following oocyte retrieval. Successful outcome is associated with a relative
      small increment in CRP on the day of embryo transfer.

PMID- 14688166
TI  - Excessive follicular response to controlled ovarian stimulation in a woman with
      menopausal FSH levels: case report.
AB  - A suspected poor responder to controlled ovarian stimulation (COS), with
      menopausal levels of follicular phase serum FSH, required coasting due to an
      excessive ovarian response. A 27 year old woman was referred to our Fertility
      Centre for ovum donation following repeated elevated, early follicular phase FSH
      levels (34.3, 27.1, 20.3 IU/l). Further investigations revealed the presence of
      antiovarian antibodies and a trial of COS, with the additional use of
      prednisolone, was proposed in view of her regular 28 day cycle. As 23 follicles
      were noted and an oestradiol level of 10,461 pmol/l following 7 days of
      stimulation with 450 IU of recombinant FSH per day, gonadotrophins were withheld
      for 9 days. Ten oocytes were retrieved and two grade I embryos were transferred.
      Pregnancy did not occur and she developed mild ovarian hyperstimulation syndrome.
      During a second cycle, multiple follicular development was again observed with an
      oestradiol level >13,200 pmol/l, despite a lower dose of gonadotrophin, and
      coasting was required for 4 days. Nineteen oocytes were collected, of which nine
      fertilized and cleaved. Two grade I embryos were replaced, leading to a singleton
      pregnancy. This patient subsequently had a vaginal delivery of a normal male baby
      at term. Young women with regular menstrual cycles and grossly elevated FSH
      levels may benefit from further investigation of autoantibodies and their ovarian
      response to exogenous gonadotrophins.

PMID- 14688167
TI  - Monozygotic triplets and monozygotic twins after ICSI and transfer of two
      blastocysts: case report.
AB  - There are data regarding the possible influences of extended embryo culture to
      the blastocyst stage as well as zona pellucida manipulation on the incidence of
      monozygotic multiples. This is interesting, as one aim of extended culture with
      embryo selection is to minimize the multiple pregnancy rate. We report, to our
      knowledge, on the first case of monozygotic twins and monozygotic triplets after
      ICSI and the transfer of two blastocysts. Monozygotic multiples after ICSI and
      blastocyst transfer and the resulting problems are another reason to encourage
      the transfer of only one blastocyst. Theories about risk factors and the
      pathophysiology of monozygotic multiples will be discussed both in terms of this
      case report and of the literature. In our opinion, the incidence of 5.9-8.9%
      monozygotic multiple occurrence after ICSI and blastocyst transfer reported in
      the literature requires that patients are informed of the uncertainties until
      this phenomenon and its risk factors are better understood.

PMID- 14688168
TI  - Does ICSI require acrosomal disruption? An ultrastructural study.
AB  - BACKGROUND: Aggressive immobilization of sperm prior to ICSI significantly
      improves fertilization rates, but the mechanism of this effect is not yet clear.
      This study was performed in order to assess the characteristics of mechanically
      immobilized human sperm by transmission electron microscope (TEM). METHODS: Sperm
      obtained from ejaculated semen samples from three different donors were
      immobilized in a standard manner for ICSI. They were then injected into the
      perivitelline space of mouse oocytes in order to be able to locate them by TEM.
      Intact motile sperm injected subzonally served as controls (n=160). Finally, the
      'carrier' oocytes were fixed and processed for TEM. RESULTS: A total of 300 sperm
      were mechanically immobilized and inserted into the perivitelline space of mouse
      oocytes. Ultrathin sections revealed consistent alterations in the acrosomal
      region including disruption of the plasma membrane, and disruption, vesiculation
      or even loss of the acrosome. Thus, all of the sperm assessed had undergone some
      disorganization of the head, in contrast to a majority of control sperm.
      CONCLUSIONS: Immobilization of sperm for ICSI by compressing and rolling the
      sperm tails induces a variable disruption and sometimes loss of the acrosome.
      This could well be a reason for the higher success rates when ICSI is performed
      using immobilized sperm.

PMID- 14688169
TI  - Analysis of chromosomal abnormalities in testicular and epididymal spermatozoa
      from azoospermic ICSI patients by fluorescence in-situ hybridization.
AB  - BACKGROUND: An increased incidence of numerical chromosomal abnormalities has
      been reported in the ejaculated spermatozoa of infertile patients. However, there
      are few cytogenetic studies of testicular and epididymal spermatozoa, and their
      results are still controversial. METHODS: Fluorescence in-situ hybridization
      (FISH) analysis of chromosomes 13, 18, 21, X and Y was performed on seven
      testicular samples and two epididymal samples from patients with obstructive
      azoospermia (OA), and on 13 testicular samples from patients with non-obstructive
      azoospermia (NOA). Five ejaculated sperm samples from normozoospermic fertile
      donors were evaluated as a control group. RESULTS: Both epididymal sperm samples
      showed normal FISH results for the parameters analysed when compared with those
      of the control group. FISH results were abnormal in 29% (two of seven) of
      testicular samples from OA patients and in 54% (seven of 13) of those from NOA
      patients, although this difference was not statistically significant. Testicular
      samples from OA patients showed a significant increase of disomy for sex
      chromosomes (P<0.01), whereas NOA patients displayed significantly higher rates
      of diploidy (P<0.0001) and disomy for chromosomes 13 (P<0.0001), 21 (P<0.001) and
      sex chromosomes (P<0.0001) than the control group. CONCLUSIONS: Testicular
      spermatozoa from azoospermic patients present increased rates of chromosomal
      abnormalities, mainly of the sex chromosomes, which are particularly high in NOA
      patients.

PMID- 14688170
TI  - CatSper gene expression in postnatal development of mouse testis and in
      subfertile men with deficient sperm motility.
AB  - BACKGROUND: The search for Ca2+ channels residing in sperm has led to the recent
      cloning and characterization of a novel gene, named CatSper, which codes for a
      unique Ca2+ channel expressed exclusively in the testis. It plays an essential
      role in sperm motility, penetration into the oocyte, and ultimately in male
      fertility. In this study, we assessed the temporal profile of CatSper gene
      expression during mouse testis development and performed a semi-quantitative
      evaluation of expression levels in a group of subfertile men which lack sperm
      motility. METHODS: A small piece of testicular tissue obtained by either multi
      site testicular biopsy or orchidectomy was used for semi-quantitative RT-PCR of
      CatSper and beta2-microglobulin (beta2m, as an internal control) genes. RESULTS:
      Our results reveal that: (i) the expression of mouse CatSper is developmentally
      regulated with a direct correlation between CatSper expression and mouse sexual
      maturation. CatSper gene expression is first detected at 3 weeks of age and
      coincides with the appearance of round spermatids in the developing mouse testis.
      (ii) There is a significant reduction in the level of CatSper gene expression (up
      to 3.5-fold difference) among patients which lack sperm motility as compared with
      patients whose infertility cannot be ascribed to a deficiency in motility (used
      as a control). CONCLUSIONS: The data obtained in this study support a potential
      role for CatSper in sperm motility and fertility in mouse and human. CatSper is
      therefore implicated as a potential target to explore the molecular mechanisms of
      male infertility.

PMID- 14688171
TI  - Relationship between ROS production, apoptosis and DNA denaturation in
      spermatozoa from patients examined for infertility.
AB  - BACKGROUND: The aim of this study was to examine the role of apoptosis and
      reactive oxygen species (ROS) in inducing DNA damage in ejaculated spermatozoa.
      METHODS: We examined ejaculated spermatozoa from 31 patients examined for
      infertility and 19 healthy donors for apoptosis, production of ROS and DNA damage
      using annexin V binding, chemiluminescence assay and sperm chromatin structure
      assay. RESULTS: The percentage of spermatozoa that underwent apoptosis in the
      whole ejaculate and mature fraction was higher in the patients than in the donors
      (P<0.001 and P=0.009, respectively). Levels of ROS in the whole ejaculate and
      immature fraction were higher in the patients than in the donors (P=0.002 and
      P=0.009). Apoptosis was significantly correlated with ROS within patients in the
      whole ejaculate [r (95% confidence interval)=0.53 (0.19-0.86)] and in the mature
      [0.71 (0.39-1.00)] and immature spermatozoa [0.75 (0.45-1.00)]. Only apoptosis
      and the DNA fragmentation index (DFI) were significantly correlated within
      patients in the whole ejaculate [0.57 (0.18-0.97)]. CONCLUSIONS: DNA damage may
      be induced by oxidative assault. Apoptosis may not contribute significantly to
      the DNA damage.

PMID- 14688172
TI  - Human sperm subpopulations: relationship between functional quality and protein
      tyrosine phosphorylation.
AB  - BACKGROUND: Human semen is composed of a heterogeneous population of sperm with
      varying degrees of structural and functional differentiation and normality, which
      result in subpopulations of different quality. METHODS: Using a discontinuous
      Percoll gradient, we separated three subsets of sperm [(45%; L45), (65%; L65) and
      (90%; L90) fractions] from normozoospermic human semen samples from healthy
      donors and proceeded to characterize their morphology, motility and
      hyperactivation, as well as their ability to undergo tyrosine phosphorylation
      under capacitating conditions. RESULTS: As expected, sperm isolated from the
      lowest density layer (L45) showed the poorest quality, displaying the smallest
      percentage of morphologically normal and motile sperm. During a capacitating
      incubation, this subset of cells also showed deficient capacity to undergo
      hyperactivation and protein tyrosine phosphorylation. Conversely, sperm isolated
      from the other layers (L65 and L90) showed a time-dependent progressive increment
      in tyrosine phosphorylation, establishing statistically significant differences
      with sperm from L45. The tyrosine phosphorylation deficiency of L45 sperm could
      be overcome when sperm from that fraction were stimulated with activators of the
      cAMP-dependent kinase (PKA) pathway (dbcAMP + pentoxifylline), pointing to the
      sperm's plasma membrane as the main site of such deficiency. CONCLUSIONS: Poor
      quality sperm isolated from a Percoll gradient display an intrinsic tyrosine
      phosphorylation deficiency, possibly caused by a plasma membrane defect, which is
      associated with their inability to undergo normal capacitation and, ultimately,
      acquire optimal fertilizing potential.

PMID- 14688173
TI  - An association between sex chromosomal aneuploidy in sperm and an abortus with
      45,X of paternal origin: possible transmission of chromosomal abnormalities
      through ICSI.
AB  - BACKGROUND: Although it has been speculated that the increased de-novo
      chromosomal abnormalities in ICSI pregnancies may be associated with an increase
      of aneuploidy in sperm from infertile men, little direct evidence exists to
      support this claim. We studied sperm from an infertile man with an abortus from
      ICSI to determine if increased sex chromosomal aneuploidy in the sperm could have
      contributed to the karyotype of the abortus. METHODS: The couple underwent ICSI
      due to severe oligozoospermia. Spontaneous aborted material was subjected to
      cytogenetic and molecular tests to ascertain the existence, type and origin of a
      chromosomal abnormality. Sperm from the man were analysed by multi-coloured
      fluorescent in-situ hybridization (FISH) with probes specific for chromosomes X,
      Y and 18. RESULTS: At 8+ weeks after embryo replacement, the patient
      spontaneously miscarried. Both cytogenetic and comparative genomic hybridization
      analysis of aborted material showed a 45,X karyotype. Origin of the abnormality
      was established as a loss of the paternal X chromosome. FISH analysis of sperm
      revealed 19.6% (1990/10,164) nullisomy for a sex chromosome and 18.6%
      (1886/10,164) with XY disomy, which is significantly increased when compared to
      controls with 0.3% (58/20,429) and 0.1% (20/20,429) respectively (P<0.0001).
      CONCLUSIONS: This study indicates that the paternal origin of the 45,X abortus
      was likely the result of a high level of nullisomy in the sperm and provides
      evidence for the transmission of chromosomal abnormality from sperm to the
      conceptus through ICSI.

PMID- 14688174
TI  - Embryo evaluation by analysing blastomere nuclei.
AB  - BACKGROUND: To create a more effective selection standard for early embryos, we
      developed a new grading system consisting of conventional morphological
      evaluation in combination with analysis of blastomere nuclei. METHODS: A total of
      744 embryos used during 459 cycles of embryo transfer on day 2 and blastocyst
      transfer were subjected to retrospective analysis. The overall implantation rate
      was 15.5% (115/744). Morphological evaluation of the embryos was performed on day
      2 by referring to both the size of blastomere and fragmentation (conventional
      method) and the nucleic features of the blastomeres--either multinucleated or
      anucleic (nuclei counting method). The implantation rate for every transferred
      embryo and blastocyst was examined. RESULTS: Although a high implantation rate
      was observed with the highest quality embryos as judged by either the
      conventional method (24.1%; 57/237) or the nuclei counting method (26.1%;
      104/399), the nuclei counting method predicted implantation rate better than the
      conventional method. The embryos that were considered to be high quality
      according to the conventional method, but low quality according to the nuclei
      counting method, had a limited implantation success rate of 6.3% (4/66). Also,
      after blastocyst transfer, implantation occurred most often when high quality
      embryos evaluated by the nuclei counting method were used (25.5%; 25/98), while
      the blastocysts from low quality embryos seldom implanted (3.2%; 2/63).
      CONCLUSIONS: When choosing which embryo to transfer, the normality of blastomere
      nuclei may be a more important index of quality than standard fragmentation
      features and/or blastomere uniformity analysis. When choosing among embryos, if
      nucleic status is identical, then embryos with the least fragmentation should be
      chosen. Moreover, in blastocyst transfer, a blastocyst whose nuclei were judged
      normal on day 2 should be selected on day 5 over any other blastocysts.

PMID- 14688175
TI  - The impact of cigarette smoking on zona pellucida thickness of oocytes and
      embryos prior to transfer into the uterine cavity.
AB  - BACKGROUND: Smoking has been reported to promote infertility. The zona pellucida
      plays an important role in fertilization and implantation. We report, for the
      first time, the effect of cigarette smoking on zona pellucida thickness of
      oocytes and embryos as one of the factors that may interfere with fertility.
      METHODS: This study comprised 169 women, grouped according to their smoking
      habits: 31 active smokers, whose husbands do not smoke; 44 active smokers, whose
      husbands smoke; 65 passive smokers, because of smoking husbands and 29 non
      smokers (women and husbands). Zona pellucida thickness was measured prospectively
      on printed photos of 903 oocytes and 456 embryos. RESULTS: The zona pellucida
      thickness of oocytes and embryos of non-smoking women was significantly thinner
      than those of active and passive smokers. However, no significant differences
      were observed in the natural ability of the zona pellucida to become thinner
      after 48 h in culture. CONCLUSIONS: Our study demonstrates that active and
      passive cigarette smoking increases the zona pellucida thickness of oocytes and
      embryos. Our findings also show that active and passive smoking has no
      significant effect on the thinning mechanism of the zona pellucida, which implies
      that it is independent of the initial zona pellucida thickness.

PMID- 14688177
TI  - Association rate between deep peritoneal endometriosis and other forms of the
      disease: pathogenetic implications.
AB  - BACKGROUND: It has been suggested recently that deep endometriosis and the other
      forms of the disease do not share a common pathogenetic mechanism. In this study,
      we hypothesize that, if this is true, deep peritoneal endometriosis and the other
      forms should not be significantly associated. METHODS: Clinical and surgical
      records of all women who were referred to the Department of Obstetrics and
      Gynecology, Clinica 'L.Mangiagalli' between January 1995 and June 2002 and who
      were diagnosed with deep peritoneal pelvic endometriosis at the time of surgery
      were retrieved. The concomitant presence of superficial endometriotic implants,
      endometriomas and pelvic adhesions was evaluated. A binomial probability
      distribution model was used to calculate the 95% confidence interval (95% CI) of
      the association rates. RESULTS: Ninety-three women with deep peritoneal
      endometriosis were identified. The presence of superficial endometriotic
      implants, endometriomas and pelvic adhesions was documented in 61.3% (95% CI 51.4
      71.2%), 50.5% (95% CI 40.3-60.7%) and 74.2% (95% CI 65.3-83.1%) of patients with
      deep endometriotic nodules, respectively. Overall, deep peritoneal endometriosis
      was the only form of the disease in only 6.5% (95% CI 2.8-12.3%) of cases. No
      relevant differences regarding these associations were observed according to the
      location and the size of the deep endometriotic nodules. CONCLUSIONS: Results
      from this study do not support the hypothesis that deep endometriosis should be
      considered as a distinct entity of the disease.

PMID- 14688176
TI  - The effects of post-surgical administration of goserelin plus anastrozole
      compared to goserelin alone in patients with severe endometriosis: a prospective
      randomized trial.
AB  - BACKGROUND: Among patients using GnRH analogues for endometriosis it has been
      postulated that peripheral and inflammation-induced in-situ aromatization of
      adrenal androgens are probably the main reasons for the high rates of failure
      during follow-up. We hypothesized that in cases with premenopausal severe
      endometriosis, use of a combination of anastrozole and goserelin to achieve
      almost maximal endocrine blockade of estrogen synthesis after conservative
      surgery may increase the pain-free interval and reduce the recurrence rates as
      compared to goserelin alone. METHODS: In a prospective randomized trial, we
      evaluated the efficacy of using either a combination of anastrozole and goserelin
      for 6 months or goserelin alone for 6 months after conservative surgery for
      severe endometriosis. The primary outcome measures were the symptom recurrence
      rates and the impact of treatment on endometriosis-related multidimensional
      score. The secondary outcome measures were the impact of allocated treatment
      regimens on menopausal quality of life and on lumbar spine bone mineral density
      (BMD). RESULTS: When we analyzed the Kaplan-Meier survival curves, we detected a
      statistically significant advantage of goserelin plus anastrozole as compared to
      goserelin only, in terms of the median time to detect symptom recurrence (>2.4
      versus 1.7 months; log-rank test; P=0.0089). This statistically significant
      advantage occurred with a relative risk of 4.3 [95% confidence interval (CI) 1.3
      9.8]. Three cases out of 40 recurred in the goserelin plus anastrozole arm
      (7.5%), whereas we detected recurrences in 14 cases out of 40 cases in the
      goserelin-only arm (35%) during the follow-up period of 24 months. Based on these
      data, the interpretation of Kaplan-Meier curves indicates that at the end of
      follow-up, 54.7 versus 10.4%, respectively, of the patients were free of
      recurrence. The mean of the differences in terms of Deltabaseline-24 months post
      medical therapy multidimensional score were statistically significant in favour
      of goserelin and anastrozole (9.2 +/- 2.1 versus 6.7 +/- 2.8; paired t-test;
      P<0.0001; 95% CI 1.5-4.0). We observed a statistically significant difference in
      suppression of estradiol concentrations and a significantly greater BMD loss at
      the end of treatment in the goserelin and anastrozole arm as compared to
      goserelin-only arm. However, this did not elicit deterioration in menopausal
      quality of life and the observed bone loss was not significant in terms of
      DeltaBMD between the groups at 2 years of treatment withdrawal. CONCLUSIONS: Six
      months of treatment with anastrozole and goserelin as compared to goserelin alone
      increased the pain-free interval and decreased symptom recurrence rates in
      patients following surgery for severe endometriosis. Furthermore, menopausal
      quality of life and BMD at 2 years after medical therapy remained unaffected.

PMID- 14688178
TI  - Concentration of soluble intercellular adhesion molecule-1 in serum samples from
      patients with endometriosis collected during the luteal phase of the menstrual
      cycle.
AB  - BACKGROUND: Soluble intercellular adhesion molecule-1 (sICAM-1), released by
      endometriotic lesions, is involved in the regulation of cytotoxic processes.
      Altered levels of sICAM-1 in the circulation could parallel its deregulation in
      the peritoneal cavity. We therefore investigated whether sICAM-1 could represent
      a serum marker for endometriosis. METHODS: sICAM-1 levels were measured by enzyme
      linked immunosorbent assay in serum samples from 176 subjects with surgically
      confirmed endometriosis (134 patients with stage I-II and 42 patients with stage
      III-IV) and 198 controls with no surgical evidence of the disease. All serum
      samples were collected during the luteal phase of the menstrual cycle. Detailed
      information about demographics, symptoms and clinical profile were collected.
      RESULTS: Mean levels of sICAM-1 appeared significantly reduced in patients with
      stage III-IV endometriosis in a crude comparison of means. However, when means
      were adjusted for potential confounders such as the pre-operative indication or
      fertility status, no significant difference between cases with stage III-IV
      disease and controls was observed. CONCLUSIONS: Serum levels of sICAM-1 during
      the luteal phase of the cycle are not able to discriminate women suffering from
      endometriosis from controls when confounders are taken into account. These
      results underline the importance of careful identification of confounders, based
      on patients' demographic and clinical data in studies aiming at discovering
      diagnostic markers for endometriosis.

PMID- 14688179
TI  - The evaluation of the effectiveness of an intrauterine-administered progestogen
      (levonorgestrel) in the symptomatic treatment of endometriosis and in the staging
      of the disease.
AB  - BACKGROUND: Medical treatment of endometriosis, a condition which significantly
      affects the quality of life in approximately 10-15% of women in the reproductive
      years, remains problematic. Although oral progestogens are effective and cheap,
      their efficacy is significantly influenced by poor compliance and systemic side
      effects. A progestogen (levonorgestrel) administered via an intrauterine system
      (Lng-IUS) has been demonstrated to improve symptoms of endometriosis; however,
      its effect on the staging of the disease has not been evaluated. The aims of this
      study were therefore to investigate the effectiveness of Lng-IUS in the
      symptomatic relief of minimal to moderate endometriosis and in the staging of the
      disease. METHODS: This was a prospective non-comparative observational study in
      which 34 women with clinically suspected and laparoscopically confirmed
      symptomatic minimal to moderate endometriosis had Lng-IUS inserted for 6 months.
      The symptom profile and stage of the disease before, during and after 6 months of
      treatment and patients' satisfaction with treatment and willingness to retain the
      device at the end of the study period were used to assess response to treatment.
      RESULTS: Of the 34 women recruited, 29 (85%) completed the study; five
      discontinued, for personal reasons (one), side effects of worsening of acne (one)
      and lower abdominal/ pelvic pain (three). Significant (P<0.05) improvements in
      severity and frequency of pain and menstrual symptoms as well as staging were
      achieved, with 68% (23) of cases electing to continue with the device after 6
      months of therapy. CONCLUSION: The levonorgestrel intrauterine system is an
      effective hormonal option for treating symptomatic endometriosis (minimal to
      moderate). It also alters the American Fertility Society staging of disease. With
      a continuation rate of 68% after 6 months, it has the potential for providing
      long-term therapy in a substantial number of sufferers, although this would
      require further study and verification.

PMID- 14688180
TI  - The rabbit nephrectomy model for training in laparoscopic surgery.
AB  - BACKGROUND: Laparoscopic surgical training is generally done with the teacher
      student model using complex exercises. This study was performed to evaluate a new
      training model that emphasizes the repetition of simple procedures. METHODS:
      Laparoscopic surgery was performed in rabbits (n=200) using conventional
      instruments. Gynaecologists (n=10) and medical students (n=10) performed a series
      of exercises during 20 full days training. Nephrectomy was chosen to evaluate and
      score laparoscopic skills, i.e. duration of surgery and complication rate, since
      it mimics the surgical challenge and involves dissection of major vessels. Each
      surgeon performed 20 nephrectomies, alternating left and right sides. RESULTS:
      Duration of surgery and complications decreased with training. For duration of
      surgery, a two-phase exponential decay learning curve, with different decays for
      gynaecologists and students, was observed. Gynaecologists achieved shorter
      operating times than students for real and calculated times in the first
      procedure (P<0.0001 and P<0.0001) and for calculated time in the last procedure
      (P=0.001). Severe complications were more frequent in students than in
      gynaecologists (P=0.0003). CONCLUSION: The rabbit nephrectomy model is suitable
      for training in laparoscopic surgery. Since it implies the repetition of short
      and well-defined exercises, progression is easier to monitor and the necessity
      for continuous supervision is less, making training less expensive.

PMID- 14688181
TI  - Prevalence of circulating procoagulant microparticles in women with recurrent
      miscarriage: a case-controlled study.
AB  - BACKGROUND: Circulating microparticles are markers of cell activation associated
      with various prothrombotic states. As hypoxia due to uteroplacental thrombosis is
      considered to be one of the causes of pregnancy loss, microparticles may be
      associated with pregnancy loss, in addition to, or as part of, other procoagulant
      states such as antiphospholipid syndrome or hereditary thrombophilias. The
      objective of this study was to examine the prevalence of circulating
      microparticles in women with recurrent pregnancy loss. METHODS: A total of 96
      women with recurrent pregnancy losses were enrolled in a case-control study and
      compared with 90 parous women. Microparticles were measured by flow cytometry
      using fluorescent anti-CD51/CD31 antibodies. RESULTS: Microparticle levels >2 SD
      above the mean of controls (57,700/ml) were detected in 12 out of 96 women with
      recurrent miscarriages (12.5%), compared with two of the 90 control women (2.2%),
      P<0.008. The titre of microparticles did not correlate with age, number of
      pregnancy losses, primary secondary or tertiary aborters status, or with
      pregnancy losses in the 1st or 2nd trimesters. CONCLUSIONS: A proportion of women
      with pregnancy loss have elevated endothelial microparticles suggesting that
      endothelial damage or activation might be associated with the pathogenesis of
      pregnancy loss.

PMID- 14688182
TI  - Markers of endometrial function in women with unexplained recurrent pregnancy
      loss: a comparison between morphologically normal and retarded endometrium.
AB  - BACKGROUND: Endometrial defect, usually described as luteal phase defect (LPD),
      is associated with recurrent miscarriage. Recurrent miscarriage has also been
      associated with the abnormal expression of various molecules by endometrial
      cells. The aim of this study was to determine if any of these molecules or cells
      could be used to distinguish LPD from in-phase endometrium. METHODS:
      Immunocytochemistry was used to compare endometrial expression of CD45+, CD56+,
      CD3+ and CD4+ cells, leukaemia inhibitory factor, interleukin-6 and estrogen and
      progesterone receptors in precisely timed endometrial biopsies obtained between
      days LH+6 and LH+11 from recurrent miscarriage women with in-phase and retarded
      endometrium. RESULTS: In all samples there was a positive correlation between the
      number of CD45+ cells and LH day and a negative correlation between progesterone
      receptor and LIF expression and LH day. A significantly lower number (P<0.05) of
      CD56+ cells in peri-implantation endometrium and a decreased mid-cycle estrogen
      level (P<0.05) was seen in women with LPD compared to in-phase endometrium when
      single analysis was carried out. However, these differences were not significant
      after application of the Bonferroni correction for multiple analysis.
      CONCLUSIONS: The results are in line with previous associations observed between
      estrogen levels and LPD and suggest that the number of CD56+ cells is different
      in LPD and in-phase endometrium, although this could be due to delayed
      endometrial development in women with LPD. Interpretation must be cautious
      because these differences could have arisen by chance.

PMID- 14688183
TI  - Decreased endovascular trophoblast invasion in first trimester pregnancies with
      high-resistance uterine artery Doppler indices.
AB  - BACKGROUND: Defective trophoblastic invasion in early pregnancy is involved in
      the pathogenesis of pre- eclampsia. This study investigates the relationship
      between Doppler assessment of uterine artery resistance and endovascular
      trophoblastic invasion in the first trimester of pregnancy. METHODS: Patients
      undergoing termination of pregnancy for non-medical reasons were categorized as
      having a low- or high-resistance uterine artery blood flow pattern by
      transabdominal Doppler ultrasound. Products of conception were examined
      histologically with regard to the extent of decidual endovascular trophoblast
      invasion. RESULTS: There were 14 low-resistance and 17 high-resistance uterine
      artery blood flow pregnancies identified at 10-14 weeks of gestation. Normal
      intradecidual endovascular trophoblast invasion was identified with a similar
      frequency in both groups (P=0.79). However, the proportion of decidual vessels
      with endovascular trophoblast invasion was significantly higher in the low
      resistance pregnancies (49%) compared with the high-resistance ones (34%,
      P=0.02). CONCLUSIONS: The findings of this study support the use of uterine
      artery Doppler investigation for the non-invasive assessment of trophoblast
      invasion in early pregnancy. Further studies are necessary to clarify the
      biological significance of these observations and their potential clinical
      applications.

PMID- 14688184
TI  - Efficacy of pulsed estrogen therapy in relatively younger patients with
      surgically induced menopause.
AB  - BACKGROUND: Pulsed estrogen therapy is a new approach in estrogen replacement
      therapy. We carried out a prospective study to evaluate the efficacy of pulsed
      estrogen therapy in relatively younger patients with surgically induced
      menopause. METHODS: Patients (n=138) <45 years old and suffering from severe
      vasomotor symptoms secondary to surgically induced menopause were included in the
      study. After the initiation of pulsed estrogen therapy (300 microg/day), the
      patients were re-evaluated every 4 weeks. The dose was increased at each follow
      up, if necessary (to a maximum of 600 microg/day). The patients who preferred
      another method after the first 12 weeks were prescribed oral conjugated estrogen
      (0.625 mg/day) and at the end of the second 12 weeks their satisfaction levels
      were assessed. RESULTS: At the end of the first 12 weeks, 26 patients were
      completely satisfied (18.8%) and 47 were moderately satisfied (34.1%), whereas 65
      concluded that the pulsed estrogen therapy they received was ineffective (47.1%).
      At the end of the second 12 weeks, all the patients were completely satisfied.
      CONCLUSION: Pulsed estrogen therapy for 12 weeks reduced the frequency of hot
      flushes in relatively younger patients with surgically induced menopause;
      however, 81.2% of patients were not completely satisfied at the end of this
      period.

PMID- 14688186
TI  - Are serum adiponectin levels really reduced in obese women with polycystic ovary
      syndrome?

PMID- 14688187
TI  - Environmental estrogens and sperm function.

PMID- 14688189
TI  - Recombinant FSH in alternative doses or versus urinary gonadotrophins for
      ovulation induction in subfertility associated with polycystic ovary syndrome.

PMID- 14688191
TI  - Sex ratio of births conceived during wartime.

PMID- 14688193
TI  - Methodological concerns regarding levels of vascular endothelial growth factor
      (VEGF) in serum of patients with endometriosis.

PMID- 14688195
TI  - Alteration of soluble adhesion molecules during aging and their modulation by
      calorie restriction.
AB  - To investigate the status of soluble adhesion molecules (sAMs) during aging, the
      present study determined protein levels of several major sAMs in serum samples
      obtained from rats at different ages. These sAMs include E-selectin, P-selectin,
      vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1
      (ICAM-1). Fischer 344 rats, ages 6, 12, 18, and 24 months, fed ad libitum (AL)
      and calorie restricted (CR) diets were used in this study. Analysis by Western
      blotting showed that the levels of all sAMs studied increased during aging in AL
      rats, but were effectively blunted in the CR rats. Total reactive oxygen
      species/reactive nitrogen species (ROS/RNS) levels were measured by fluorescent
      probe 2',7'-dichlorofluorescin diacetate. Increased ROS/RNS levels were found to
      coincide with increased levels of superoxide-generating xanthine oxidase in serum
      during aging, but were found suppressed by CR. Increases in sAMs levels were
      duplicated in another experiment in which young (13-month-old) and old (31-month
      old) rats were injected with proinflammatory lipopolysaccharide. These findings
      suggest that the altered expressions of sAMs may be due to increased oxidative
      stress with advanced age and that these increases were prevented by CR through
      its antioxidative action.

PMID- 14688196
TI  - Responses of vascular endothelial cells to angiogenic signaling are important for
      tumor cell survival.
AB  - Neoplastic cells overexpress several angiogenic cytokines, which stimulate
      neovascularization. Whether the responses of the host endothelial cells to these
      signaling molecules affect tumor cells during early tumorigenesis has not been
      investigated. We investigated pre-angiogenic tumor cell survival and angiogenesis
      initiation by two murine tumor lines (4T1 mammary carcinoma and B16 melanoma),
      which constitutively expressed GFP, in dorsal skin-fold window chambers of mice
      treated with extracellular domain of Tie-2 (ExTek) or bFGF. ExTek reduced tumor
      cell survival, retarded tumor growth, and inhibited angiogenesis onset compared
      with controls. bFGF increased tumor cell survival and promoted earlier
      angiogenesis and tumor growth. Neither bFGF nor ExTek affected cell proliferation
      in vitro. RT-PCR showed mRNA expression of bFGF receptor 2 (FGFR2) IIIb, which
      does not bind bFGF efficiently, by 4T1 cells and B16 cells express FGFR1 but not
      FGFR2. B16 cells expressed angiopoietin (Ang) 2, but neither cell line expresses
      Ang1. Both tumor lines express VEGF. These findings suggested that effects of
      bFGF and ExTek on tumor cell survival and angiogenesis were not due to direct
      action but were instead a result of paracrine factors secreted by endothelial
      cells. These subsequent signals from endothelial cells promote early survival and
      proliferation of disseminated tumor cells before onset of angiogenesis.

PMID- 14688197
TI  - Identification and enrichment of spermatogonial stem cells displaying side
      population phenotype in immature mouse testis.
AB  - In mammals, spermatogenesis is maintained by spermatogonial stem cells (SSC). In
      their niche, SSC divide to self-maintain and to produce a transit-amplifying
      population that eventually enters the meiotic cycle to give rise to spermatozoa.
      The low number of SSC and the lack of specific markers hinder their isolation and
      enrichment. Stem cells in several adult tissues can be identified by using their
      verapamil-sensitive Hoechst dye-effluxing properties, which define the
      characteristic "side population" (SP). Here we show, by multicolor flow
      cytometric analysis, that immature mouse testis contains a "side-population" (T
      SP), which is Sca-1pos, Ep-CAMpos, EE2 pos, alpha6-integrin pos, and alpha(v)
      integrin neg. A 13-fold enrichment in SSC activity was observed when sorted T-SP
      cells from ROSA 26 mice were transplanted in busulfan-treated mouse testis.
      Whereas an incomplete range of spermatogenic stages was encountered two months
      after transplantation of unsorted testicular cells, the transplantation of T-SP
      cells generated all associations of mouse germ cells representing the full range
      of spermatogenic stages. These data suggest that Hoechst staining and cell
      sorting might provide a novel approach to SSC enrichment in mammals.

PMID- 14688198
TI  - Short telomeres protect from diet-induced atherosclerosis in apolipoprotein E
      null mice.
AB  - By imposing a replicative defect in most somatic cells, gradual telomere
      attrition during aging is thought to progressively impair cellular function and
      viability and may contribute to age-related disease. Immune cells play important
      roles in all phases of atherosclerosis, a multifactorial disease that prevails
      within the elderly. Because shorter telomeres have been found in circulating
      blood leukocytes of human patients with advanced coronary atherosclerosis, it has
      been suggested that telomere shortening may predispose the organism to atheroma
      development. In this study, we assessed the impact of telomere attrition on
      atherogenesis induced by dietary cholesterol in apolipoprotein E (apoE)-deficient
      mice, a well-established model of experimental atherosclerosis that recapitulates
      important aspects of the human disease. Our study shows that late-generation mice
      doubly deficient in apoE and telomerase RNA experience telomere attrition and a
      substantial reduction of atherosclerosis compared with control mice with intact
      telomerase, in spite of sustained hypercholesterolemia in response to the
      atherogenic diet. Short telomeres impaired the proliferation of both lymphocytes
      and macrophages, an important step in atherosclerosis development. Therefore,
      telomere exhaustion resulting in replicative immunosenescence may serve as a
      mechanism for restricting atheroma progression.

PMID- 14688199
TI  - Regulatory role of C5a in LPS-induced IL-6 production by neutrophils during
      sepsis.
AB  - Experimental sepsis in rodents occurring after cecal ligation/puncture (CLP) is
      associated with excessive complement activation and a systemic inflammatory
      response. The proinflammatory mediator IL-6 has recently been shown to be an
      important inducer of the C5a receptor (C5aR) during sepsis. We now provide
      evidence that serum IL-6 production during sepsis in rats was reduced in
      neutrophil-depleted animals and that absence of C5aR in mice as well as antibody
      blockade of C5a in rats significantly reduced serum levels of IL-6 during sepsis.
      Lipopolysaccharide (LPS)-induced production in vitro of IL-6 by neutrophils was
      significantly enhanced in the co-presence of C5a, likely due to transcriptional
      up-regulation of IL-6. Production of IL-6 in neutrophils by LPS was NF-kappaB
      dependent (but not on the presence of p50) and dependent on phosphorylation of
      p38-mitogen activated protein kinase (MAPK) as well as p44/p42 MAPK (ERK1/2) but
      not on phosphorylation of c-Jun N-terminal kinases (JNK1/2). C5a stimulation of
      neutrophils elicited a rapid phosphorylation of ERK1/2 and p38 MAPK. Accordingly,
      we suggest that induction of IL-6 after CLP is neutrophil and C5a/C5aR dependent,
      likely due to the ability of C5a to cause activation of ERK1/2 and p38 MAPK
      signaling pathways.

PMID- 14688200
TI  - Adipose tissue energy metabolism: altered gene expression profile of mice
      subjected to long-term caloric restriction.
AB  - We investigated the influences of short-term and lifespan-prolonging long-term
      caloric restriction (LCR) on gene expression in white adipose tissue (WAT). Over
      11,000 genes were examined using high-density oligonucleotide microarrays in four
      groups of 10- to 11-month-old male C57Bl6 mice that were either fasted for 18 h
      before death (F), subjected to short-term caloric restriction for 23 days (SCR),
      or LCR for 9 months and compared with nonfasted control (CO) mice. Only a few
      transcripts of F and SCR were differentially expressed compared with CO mice. In
      contrast, 345 transcripts of 6,266 genes found to be expressed in WAT were
      altered significantly by LCR. The expression of several genes encoding proteins
      involved in energy metabolism was increased by LCR. Further, many of the shifts
      in gene expression after LCR are known to occur during adipocyte differentiation.
      Selected LCR-associated alterations of gene expression were supported by
      quantitative reverse transcriptase-polymerase chain reaction, histology, and
      histochemical examinations. Our data provide new insights on the metabolic state
      associated with aging retardation by LCR.

PMID- 14688201
TI  - Neuronal injury mediated via stimulation of microglial toll-like receptor-9
      (TLR9).
AB  - Innate immune cells express toll-like receptor-9 (TLR9) and respond to
      unmethylated, CG dinucleotide motif-rich DNA released from bacteria during
      infection or endogenous cells during autoimmune tissue injury. Oligonucleotides
      containing CG dinucleotide (CpG-DNA) mimic the effect of unmethylated DNA and
      stimulate TLR9. CpG-DNA was cytotoxic to neurons in organotypic brain cultures.
      Neurotoxicity of CpG-DNA was mediated via microglial cells and started primarily
      from neurites as determined by time-lapse imaging of enhanced green fluorescent
      protein (EGFP)-transfected neurons. Cultured brain microglial cells expressed
      TLR9 and responded to CpG-DNA by production of the inflammatory mediators nitric
      oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). Blockade of NO synthase
      and TNF-alpha prevented damage of neurites and neurotoxicity of CpG-DNA. The data
      suggest that stimulation of microglia via TLR9 and subsequent release of NO and
      TNF-alpha is a major source of neurotoxicity in bacterial and autoimmune brain
      tissue injury.

PMID- 14688202
TI  - Protein kinase C regulates functional coupling of beta1-adrenergic receptors to
      Gi/o-mediated responses in cardiac myocytes.
AB  - The effect of protein kinase C (PKC) activation on beta1-adrenergic receptor
      (beta1-AR) regulation of the cardiac L-type Ca2+ current (ICa,L) was studied
      using the whole-cell patch clamp technique. Treatment of guinea pig ventricular
      myocytes with phorbol-12,13-dibutyrate (PDBu) caused a significant decrease in
      ICa,L sensitivity to stimulation by submaximal beta1-AR activation using
      isoproterenol (Iso). This decrease in sensitivity was also associated with the
      ability of higher concentrations of Iso to directly inhibit the stimulatory
      response. PDBu treatment produced similar effects on H2 histamine receptor
      mediated ICa,L responses. In the presence of PDBu, higher concentrations of Iso
      inhibited the histamine stimulated ICa,L, and this effect was blocked by a
      selective beta1-AR antagonist. Higher concentrations of histamine also inhibited
      the Iso stimulated ICa,L, and this effect was blocked by a selective H2 receptor
      antagonist. The effects of PDBu were blocked by the PKC inhibitor
      bisindolylmaleimide I, and they were not mimicked by the inactive phorbol ester
      4alpha-phorbol-12,13-didecanoate. The inhibitory effects of Iso and histamine
      were significantly reduced when Gi/o mediated responses were blocked with
      pertussis toxin. These results suggest that PKC promotes coupling of cardiac
      beta1-adrenergic and H2 histamine receptors to Gi/o mediated inhibitory
      responses.

PMID- 14688203
TI  - Antibodies reactive to heat shock protein 90 induce oligodendrocyte precursor
      cell death in culture. Implications for demyelination in multiple sclerosis.
AB  - Oligodendrocyte precursor cells (OPCs) are extremely efficient at remyelination.
      These cells persist in the adult human central nervous system and can
      proliferate. However, the failure to remyelinate is a pathological characteristic
      of the human demyelinating disease multiple sclerosis (MS), which suggests that
      these cells are ineffective in this disorder. This paper reports that IgG
      antibodies in the cerebrospinal fluid (CSF) of MS patients specifically recognize
      an antigen on OPCs in culture. Control patients were found not to possess these
      antibodies. The antigen was immunoprecipitated in cell extracts from cultures
      with purified IgG from MS CSF. Peptide mass fingerprinting identified it as the
      beta type of heat shock protein 90 (Hsp90). Two-dimensional electrophoresis and
      immunoblot showed that this antigen in fact corresponds to two specific isoforms
      of Hsp90beta. Several control assays using monoclonal and polyclonal anti-Hsp90
      antibodies confirmed the specific expression of Hsp90 on OPCs. Labeling OPCs in
      vivo with MS CSF and anti-Hsp90 antibodies and subsequent immunofluorescence
      confocal microscopy located the antigen on the cell surface. The binding of CSF
      antibodies from MS patients to the OPC surface led to complement activation and
      significant extinction of the OPC population. These results suggest that OPCs may
      be a target of anti-Hsp90 antibodies in MS patients and that this could prevent
      remyelination.

PMID- 14688204
TI  - Role of direct RhoA-phospholipase D1 interaction in mediating adenosine-induced
      protection from cardiac ischemia.
AB  - Activation of adenosine A1 or A3 receptors protects heart cells from ischemia
      induced injury. The A3 receptor signals via RhoA and phospholipase D (PLD) to
      induce cardioprotection. The objective of the study was to investigate how RhoA
      activates PLD to achieve the anti-ischemic effect of adenosine A3 receptors. In
      an established cardiac myocyte model of preconditioning using the cultured chick
      embryo heart cells, overexpression of the RhoA-noninteracting PLD1 mutant I870R
      selectively blocked the A3 agonist (Cl-IBMECA, 10 nM)-induced cardioprotection.
      I870R caused a significantly higher percentage of cardiac cells killed in A3
      agonist-treated than in A1 agonist (CCPA, 10 nM)-treated myocytes (ANOVA and
      posttest comparison, P<0.01). Consistent with its inhibitory effect on the PLD
      activity, I870R attenuated the Cl-IBMECA-mediated PLD activation. Cl-IBMECA
      caused a 41 +/- 15% increase in PLD activity in mock-transfected myocytes
      (P<0.01, paired t test) while having only a slight stimulatory effect on the PLD
      activity in I870R-transfected cells. To further test the anti-ischemic role of a
      direct RhoA-PLD1 interaction, atrial cardiac myocytes were rendered null for
      native adenosine receptors by treatment with irreversible A1 antagonist m-DITC
      XAC and were selectively transfected with the human adenosine A1 or A3 receptor
      cDNA individually or they were cotransfected with cDNAs encoding either receptor
      plus I870R. I870R preferentially inhibited the human A3 receptor-mediated
      protection from ischemia. The RhoA-noninteracting PLD1 mutant caused a
      significantly higher percentage of cardiac cells killed in myocytes cotransfected
      with the human A3 receptor than in those cells expressing the human A1 receptor
      (ANOVA and posttest comparison, P<0.01). The present data provided the first
      demonstration of a novel physiological role for the direct RhoA-PLD1 interaction,
      that of potent protection from cardiac ischemia. The study further supported the
      concept that a divergent signaling mechanism mediates the anti-ischemic effect of
      adenosine A1 and A3 receptors.

PMID- 14688205
TI  - Integrin alphaIIbbeta3-specific synthetic human monoclonal antibodies and HCDR3
      peptides that potently inhibit platelet aggregation.
AB  - The interaction of fibrinogen with integrin alphaIIbbeta3 (GPIIb/IIIa), in part
      mediated by an RGD tripeptide motif, is an essential step in platelet
      aggregation. Based on their inhibition of platelet aggregation, three integrin
      alphaIIbbeta3 inhibitors are clinically approved. The clinically most widely used
      integrin alphaIIbbeta3 inhibitor abciximab is a chimeric mouse/human antibody
      that induces thrombocytopenia, often severe, in 1-2% of patients due to a human
      anti-mouse antibody (HAMA) response. In addition, unlike other ligands mimicking
      small molecular drugs, abciximab cross-reacts with integrin alphavbeta3 and
      alphaMbeta2. Here we used phage display to select monoclonal antibodies specific
      to integrin alphaIIbbeta3 from a synthetic human antibody library based on the
      randomized HCDR3 sequence VGXXXRADXXXYAMDV. The selected antibodies revealed a
      strong consensus in HCDR3 (V(V/W)CRAD(K/R)RC) and high specificity toward
      integrin alphaIIbbeta3 but not to other RGD binding integrins such as
      alphavbeta3, alphavbeta5, and alpha5beta1. The selected antibodies as well as
      three synthetic peptides (VWCRADRRC, VWCRADKRC, and VVCRADRRC) whose sequences
      were derived from the HCDR3 sequences of the selected antibodies strongly
      inhibited the interaction between integrin alphaIIbbeta3 and fibrinogen and
      platelet aggregation ex vivo. To our knowledge, these are the first fully human
      monoclonal antibodies that are specific to integrin alphaIIbbeta3 and can
      potently inhibit platelet aggregation.

PMID- 14688206
TI  - Proteolytic processing of laminin-5 by MT1-MMP in tissues and its effects on
      epithelial cell morphology.
AB  - The extracellular matrix macromolecule laminin-5 (Ln-5) is converted by matrix
      metalloproteinases (MMP) MT1-MMP and MMP-2 into a migration-promoting substrate
      in vitro. We now report that cleavage of Ln-5 by MT1-MMP occurs in vivo and
      affects epithelial tissue organization and probably Ln-5 turnover. In MT1-MMP
      knockout (KO) mice, the kidneys showed increased levels of total Ln-5 gamma2
      subunit, but significantly reduced amounts of gamma2', an amino-terminal
      truncated proteolytic form of gamma2. The kidney tubular epithelia of KO animals
      were poorly differentiated, a phenotype reminiscent of human congenital mixed
      hypoplastic/dysplastic disorders. To establish a better link between Ln-5
      proteolytic cleavage and epithelial morphology, MT1-MMP expression was
      reconstituted by transfection of MT1-MMP into a Ln-5 positive, MT1-MMP deficient
      epithelial cell line. MT1-MMP transfectants demonstrated increased levels of
      processed Ln-5 gamma2 chain and enhanced spreading on Ln-5, but not fibronectin.
      Recombinant MT1-MMP cleaved gamma2 constructs in vitro at a known in vivo gamma2
      gamma2' processing site. These results strongly indicate that Ln-5 is a
      physiological substrate of MT1-MMP in vivo. Proteolytic processing of gamma2
      subunit by MT1-MMP may influence Ln-5 turnover in epithelial basement membranes
      and affect epithelial morphogenesis.

PMID- 14688207
TI  - Expression profiling and identification of novel genes involved in myogenic
      differentiation.
AB  - Skeletal muscle differentiation is a complex, highly coordinated process that
      relies on precise temporal gene expression patterns. To better understand this
      cascade of transcriptional events, we used expression profiling to analyze gene
      expression in a 12-day time course of differentiating C2C12 myoblasts. Cluster
      analysis specific for time-ordered microarray experiments classified 2895 genes
      and ESTs with variable expression levels between proliferating and
      differentiating cells into 22 clusters with distinct expression patterns during
      myogenesis. Expression patterns for several known and novel genes were
      independently confirmed by real-time quantitative RT-PCR and/or Western blotting
      and immunofluorescence. MyoD and MEF family members exhibited unique expression
      kinetics that were highly coordinated with cell-cycle withdrawal regulators.
      Among genes with peak expression levels during cell cycle withdrawal were Vcam1,
      Itgb3, Itga5, Vcl, as well as Ptger4, a gene not previously associated with the
      process of myogenesis. One interesting uncharacterized transcript that is highly
      induced during myogenesis encodes several immunoglobulin repeats with sequence
      similarity to titin, a large sarcomeric protein. These data sets identify many
      additional uncharacterized transcripts that may play important functions in
      muscle cell proliferation and differentiation and provide a baseline for
      comparison with C2C12 cells expressing various mutant genes involved in myopathic
      disorders.

PMID- 14688208
TI  - Long-term in vivo transduction of neurons throughout the rat CNS using novel
      helper-dependent CAV-2 vectors.
AB  - Numerous genetic and environmental causes, variable pathophysiologies, and the
      blood-brain barrier create a formidable challenge for the study and treatment of
      neurodegenerative diseases affecting the central nervous system. Although there
      are many intracellular strategies to address neurodegeneration, for example,
      which transgene to use, one fundamental criterion for the long-term survival of
      neurons may be their genetic modification. Here, we describe the generation and
      in vivo efficacy of helper-dependent canine adenovirus (CAV-2) vectors that
      preferentially transduced neurons and efficiently trafficked via axonal
      retrograde transport. We used a flexible strategy and the synergy between
      Cre/loxP and nonlethal packaging-defective helper vectors to generate high titer
      helper-dependent vector stocks. One year after striatal injections in the rat
      brain, we found stable, high-level expression in striatal neurons, ~50% of the
      dopaminergic neurons of the substantia nigra, and the cholinergic neurons in the
      basal nuclei of Meynert. Due to the intrinsic properties of helper-dependent CAV
      2 vectors (27-kb cloning capacity; low preexisting, innate, and induced
      immunogenicity; retrograde transport; and long-term transgene expression), they
      will aid fundamental and applied studies in neurobiology. Moreover, helper
      dependent CAV-2 vectors may be clinically relevant for the treatment of many
      neurodegenerative diseases.

PMID- 14688209
TI  - Overexpression of HSP70 in mouse skeletal muscle protects against muscle damage
      and age-related muscle dysfunction.
AB  - Ageing is associated with skeletal muscle atrophy, a deficit in force generation,
      an increased susceptibility to contraction-induced injury, and a permanent force
      deficit following severe injury. Muscles of young mice adapt rapidly following
      exercise by an increase in the production of heat shock proteins (HSPs), whereas
      muscles of old mice show a severely diminished response. We hypothesized that
      overexpression of HSP70 in muscle throughout life would reduce age-related
      changes in function. The maximum tetanic force of extensor digitorum longus (EDL)
      muscles of adult and old wild-type (WT) and HSP70 overexpressor transgenic mice
      was determined. EDL muscles were subjected to damaging lengthening contractions
      and the ability to generate force was assessed for up to 28 days following the
      contractions. Overexpression of HSP70 in muscles of old transgenic mice prevented
      the specific force deficit observed in muscles of old WT mice. The complete
      recovery of muscles of old HSP70 transgenic mice by 14 days following the
      contraction protocol was in contrast to the 44% force deficit, which remained in
      muscles of old WT mice at 28 days following the protocol. These data indicate
      that a diminished production of HSP70 in muscles of old mammals has a major
      effect on age-related functional deficits.

PMID- 14688210
TI  - An essential role for angiotensin II type 1a receptor in pregnancy-associated
      hypertension with intrauterine growth retardation.
AB  - Little is known about an in vivo significance of angiotensin II Type-1 receptor
      (AT1) for pregnancy-associated diseases, including hypertension and intrauterine
      growth retardation (IUGR). We previously demonstrated that female mice carrying
      the human angiotensinogen gene (hAG+/+), when mated with human renin transgenic
      (hRN+/+) male mice, displayed hypertension in late pregnancy due to secretion of
      human renin from the fetal side into the maternal circulation. In the present
      study, to investigate a role for AT1 in pregnancy-associated hypertension, we
      generated a new strain of hAG+/+/mAT1a-/- mice by genetically deleting the AT1a
      gene from hAG+/+ mice. When mated with hRN+/+ male mice, excessive increases in
      human renin, angiotensin, and plasma renin activity were detected in the plasma
      of pregnant hAG+/+/mAT1a-/- mice as found in that of pregnant hAG+/+ mice.
      Surprisingly, however, blood pressure of hAG+/+/mAT1a-/- mice was not elevated in
      late pregnancy despite the presence of AT1b, a subtype of AT1. The maternal and
      fetal defects, such as cardiac and placental abnormalities, and IUGR observed in
      pregnant hypertensive hAG+/+ mice were not recognized in pregnant hAG+/+/mAT1a-/-
      mice. The limited term administration of AT1 antagonists to hypertensive hAG+/+
      mice in late pregnancy dramatically improved hypertension and IUGR, showing the
      clinical importance of AT1a.

PMID- 14688211
TI  - Hepatitis B virus X protein induces angiogenesis by stabilizing hypoxia-inducible
      factor-1alpha.
AB  - Hepatitis B virus X protein (HBx) is closely involved in the development of
      hepatocellular carcinoma, a highly vascularized solid tumor. Here we show that
      HBx increases the transcriptional activity and protein level of hypoxia-inducible
      factor-1alpha (HIF-1alpha) under both normoxic and hypoxic conditions, and it
      also stimulates angiogenesis. HBx directly interacted with the bHLH/PAS domain of
      HIF-1alpha but not with the von Hippel-Lindau protein (pVHL). HBx decreased the
      binding of pVHL to HIF-1alpha and prevented ubiquitin-dependent degradation of
      HIF-1alpha. In HBx-transgenic mice, HIF-1alpha and vascular endothelial growth
      factor were strongly detected in the dysplastic lesion, where HBx was also more
      highly expressed than in the non-neoplastic region of the liver. An
      immunohistochemical study showed that microvessels are more abundant in the
      dysplastic lesion than in the non-neoplastic region. Our data suggest that HBx
      stabilizes HIF-1alpha and leads to angiogenesis during hepatocarcinogenesis.

PMID- 14688212
TI  - Preservation of immunoreactivity and fine structure of adult C. elegans tissues
      using high-pressure freezing.
AB  - The location of a protein labeled by immunogold techniques can be resolved under
      an electron beam to within nanometers of its epitope, a resolution that makes
      immunoelectron microscopy a valuable tool for studies of cell biology. However,
      tissues in the nematode Caenorhabditis elegans are difficult to preserve for
      immunoelectron microscopic studies. The animal's cuticle slows the diffusion of
      solutions into the animal and thus makes it difficult to preserve both
      immunoreactivity and cell morphology. Here we describe a protocol that
      circumvents these problems. Specifically, we instantly immobilized tissue in
      vitreous ice by freezing living adult animals under high pressure. Frozen
      specimens were then chemically fixed, dehydrated, and embedded at low
      temperatures. As a result, chemical diffusion across the cuticle could occur over
      an extended period without morphological deterioration. We show that this method
      is capable of preserving both cell morphology, including fine structures, and
      immunoreactivity. Therefore, it provides a means to characterize the localization
      of endogenous proteins and exogenous proteins, such as the green fluorescent
      protein (GFP), with respect to subcellular compartments in C. elegans tissues by
      using postembedding immunogold labeling.

PMID- 14688213
TI  - Application of quantum dots as probes for correlative fluorescence, conventional,
      and energy-filtered transmission electron microscopy.
AB  - Luminescent semiconductor quantum dots (QDs) are a new class of fluorescent label
      with wide-ranging applications for cell imaging. The electron density and
      elemental composition of these materials permit the extension of their use as
      probes in conventional electron microscopy (TEM) and energy-filtered TEM (EFTEM).
      Here we illustrate the feasibility of using streptavidin-conjugated QDs as TEM
      tags by labeling a nuclear protein on cell sections and obtaining correlative
      fluorescence and TEM data. We also show that QD probes can be employed in
      conjunction with immunogold for co-localization of proteins at the
      ultrastructural level. Furthermore, by obtaining cadmium elemental maps of
      CdSe/ZnS QDs distributed on a nuclear structure, we demonstrate the potential of
      QDs for co-localization of multiple proteins when used in combination with EFTEM.

PMID- 14688214
TI  - Immunohistochemical assessment of the peripheral benzodiazepine receptor in human
      tissues.
AB  - Exhaustive analysis of the location of the peripheral benzodiazepine receptor
      (PBR) both at the subcellular and the tissue level is warranted to gain a better
      understanding of its biological roles. To date, many studies have been performed
      in animal models, such as rat, mouse, and pig, that yielded important
      information. However, only a few reports were dedicated to the analysis of PBR
      expression in humans. To enlarge on previous studies, we investigated PBR
      expression in different human organs using the monoclonal antibody 8D7 that
      specifically recognized the human PBR. First, we performed electron microscopic
      analysis that for the first time unambiguously demonstrated the localization of
      the PBR on the outer mitochondrial membrane. Second, focusing our analysis on
      human tissues for which information on PBR expression is sparse (lung, stomach,
      small intestine, colon, thyroid, adrenal gland, pancreas, breast, prostate,
      ovary), we found that PBR exhibits selective localization. This characterization
      of PBR localization in human tissues should provide important insights for the
      understanding of PBR functions.

PMID- 14688215
TI  - Expression of cytokines (TNF-alpha, IL-1alpha, and IL-2) in chronic hepatitis C:
      comparative hybridocytochemical and immunocytochemical study in children and
      adult patients.
AB  - Hepatitis C virus (HCV) is one of the principal causes of hepatitis, which in
      more than 80% of cases leads to chronic lesions in the liver and involvement of
      extrahepatic organs. It remains unknown why the infection so frequently turns
      chronic, independently of patient age. Using immunocytochemistry (IHC) and in
      situ hybridization (ISH) (both linked to the ImmunoMax technique) we examined
      cell sources of TNF-alpha, IL-1alpha, and IL-2 in control and HCV-infected
      children and adults. We demonstrated augmented expression of all the cytokines in
      HCV-infected patients compared to controls. No differences were detected in
      amounts of studied transcripts or cytokine proteins between biopsies taken from
      HCV-infected children and adults. Expression of TNF-alpha was localized mainly in
      liver sinusoidal cells (macrophages, endothelial cells). A high proportion of
      hepatocytes demonstrated expression of TNF-alpha, IL-1alpha, and IL-2. In both
      groups of patients, higher amounts of cytokine proteins than studied transcripts
      were demonstrated. The augmented expression of TNF-alpha, IL-1alpha, and IL-2 in
      liver with a similar proportion of involved cells (mainly hepatocytes) in
      children and in adults points to participation of the cytokines in the
      pathogenesis of chronic hepatitis C. The expression is insufficient to terminate
      the infection and may be linked with the comparably frequent chronic
      transformation of HCV infection noted in children and adults.

PMID- 14688216
TI  - In vivo angiogenic phenotype of endothelial cells and pericytes induced by
      vascular endothelial growth factor-A.
AB  - VEGF-A is a major angiogenesis and permeability factor. Its cellular effects,
      which can be used as targets in anti-angiogenesis therapy, have mainly been
      studied in vitro using endothelial cell cultures. The purpose of the present
      study was to further characterize these effects in vivo in vascular endothelial
      cells and pericytes, in an experimental monkey model of VEGF-A-induced iris
      neovascularization. Two cynomolgus monkeys (Macaca fascicularis) received four
      injections of 0.5 microg VEGF-A in the vitreous of one eye and PBS in the other
      eye. After sacrifice at day 9, eyes were enucleated and iris samples were snap
      frozen for immunohistochemistry (IHC) and stained with a panel of antibodies
      recognizing endothelial and pericyte determinants related to angiogenesis and
      permeability. After VEGF-A treatment, the pre-existing iris vasculature showed
      increased permeability, hypertrophy, and activation, as demonstrated by increased
      staining of CD31, PAL-E, tPA, uPA, uPAR, Glut-1, and alphavbeta3 and alphavbeta5
      integrins, VEGF receptors VEGFR-1, -2 and -3, and Tie-2 in endothelial cells, and
      of NG2 proteoglycan, uPA, uPAR, integrins and VEGFR-1 in pericytes. Vascular
      sprouts at the anterior surface of the iris were positive for the same antigens
      except for tPA, Glut-1, and Tie-2, which were notably absent. Moreover, in these
      sprouts VEGFR-2 and VEGFR-3 expression was very high in endothelial cells,
      whereas many pericytes were present that were positive for PDGFR-beta, VEGFR-1,
      and NG2 proteoglycan and negative for alpha-SMA. In conclusion, proteins that
      play a role in angiogenesis are upregulated in both pre-existing and newly formed
      iris vasculature after treatment with VEGF-A. VEGF-A induces hypertrophy and loss
      of barrier function in pre-existing vessels, and induces angiogenic sprouting,
      characterized by marked expression of VEGFR-3 and lack of expression of tPA and
      Tie-2 in endothelial cells, and lack of alpha-SMA in pericytes. Our in vivo study
      indicates a role for alpha-SMA-negative pericytes in early stages of
      angiogenesis. Therefore, our findings shed new light on the temporal and spatial
      role of several proteins in the angiogenic cascade in vivo.

PMID- 14688217
TI  - Individual subtypes of enteroendocrine cells in the mouse small intestine exhibit
      unique patterns of inositol 1,4,5-trisphosphate receptor expression.
AB  - Enteroendocrine cells are a complex population of intestinal epithelial cells
      whose hormones play critical roles in regulating gastrointestinal and whole
      animal physiology. There are many subpopulations of enteroendocrine cells based
      on the major hormone(s) produced by individual cells. Intracellular calcium plays
      a critical role in regulating hormone release. Inositol 1,4,5-trisphophate (IP3)
      receptors regulate calcium mobilization from endoplasmic reticulum-derived
      calcium stores in many endocrine and excitatory cells and are expressed in the
      intestine. However, the specific subtypes of enteroendocrine cells that express
      these receptors have not been reported. Immunohistochemical (IHC) studies
      revealed that enteroendocrine cells did not express detectable levels of type 2
      IP3 receptors, whereas nearly all enteroendocrine cells that produced
      chromogranin A and/or serotonin expressed type 1 and type 3 IP3 receptors.
      Conversely, enteroendocrine cells that produced glucose-dependent insulinotropic
      polypeptide, glucagon-like peptide-1, cholecystokinin, or somatostatin did not
      express detectable levels of any IP3 receptors. Subsets of enteroendocrine cells
      that produced substance P or secretin expressed type 1 (33% or 18%, respectively)
      and type 3 (10% or 62%, respectively) IP3 receptors. Thus, different subtypes of
      enteroendocrine cells, as well as individual cells that express a particular
      hormone, exhibit remarkable heterogeneity in the molecular machineries that
      regulate hormone release in vivo. These results suggest that therapeutic agents
      can be developed that could potentially inhibit or promote secretion of hormones
      from specific subtypes of enteroendocrine cells.

PMID- 14688218
TI  - Correlated endothelial caveolin overexpression and increased transcytosis in
      experimental diabetes.
AB  - We investigated the mechanism by which diabetes renders the capillary endothelium
      more permeable to macromolecules in the lungs of short-term diabetic rats. We
      used quantitative immunocytochemistry (ICC) to comparatively assess the
      permeability of alveolar capillaries to serum albumin in diabetic and
      normoglycemic animals. The effect of diabetes on the population of endothelial
      caveolae was evaluated by morphometry and by ICC and immunochemical
      quantification of the amount of caveolin in the whole cell or associated with the
      purified endothelial plasma membrane. A net increase in the amount of serum
      albumin taken up by the plasmalemmal vesicles of alveolar endothelial cells and
      transported to the interstitium was documented in diabetic animals.
      Interendothelial junctions were not permeated by albumin molecules. The alveolar
      endothelial cells of hyperglycemic rats contain more caveolae (1.3-fold),
      accounting for a larger (1.5-fold) fraction of the endothelial volume than those
      of normal animals. The hypertrophy of the caveolar compartment is accompanied by
      overexpression of endothelial caveolin 1. Although the aggregated thickness of
      the endothelial and alveolar epithelium basement membranes increases in diabetes
      (1.3-fold), the porosity of this structure appears to be unchanged. Capillary
      hyperpermeability to plasma macromolecules recorded in the early phase of
      diabetes is explained by an intensification of transendothelial vesicular
      transport and not by the destabilization of the interendothelial junctions.

PMID- 14688219
TI  - High-pressure freezing of isolated gastric glands provides new insight into the
      fine structure and subcellular localization of H+/K+-ATPase in gastric parietal
      cells.
AB  - High-pressure freezing (HPF) is currently the most reliable method to obtain an
      adequately frozen sample for high-resolution morphological evaluation. Here we
      applied the HPF technique to isolated rabbit gastric glands to reveal structural
      evidence that may be correlated with functional activity of gastric parietal
      cells. This approach provided well-preserved fine structure and excellent
      antigenicity of several parietal cell proteins. Microtubules were abundant in the
      cytoplasm and frequently appeared to be associating with tubulovesicles.
      Interestingly, many electron-dense coated vesicles were apparent around the
      intracellular canaliculi (IC) of resting parietal cells, consistent with active
      membrane retrieval from the apical membranes. Immunolabeling of H+/K+-ATPase was
      evident on the endocytic components (e.g., multivesicular bodies) and
      tubulovesicles. After histamine stimulation, the parietal cells
      characteristically showed expanded IC membranes with varied features of their
      apical microvilli. The labeling density of H+/K+-ATPase was four-fold higher on
      the IC membrane of stimulated parietal cells than on that of resting parietal
      cells. Immunolabeling of ezrin was clearly identified on the IC and basolateral
      membranes of parietal cells, corresponding to their F-actin-rich sites. The
      present findings provide a new insight into the correlation of cell structure and
      function in gastric parietal cells.

PMID- 14688220
TI  - Ultrastructural localization of platelet endothelial cell adhesion molecule
      (PECAM-1, CD31) in vascular endothelium.
AB  - The distribution of platelet endothelial cell adhesion molecule (PECAM-1, CD31)
      in vascular endothelium has been disputed. Originally reported to be highly
      concentrated at interendothelial cell contacts, recent studies have claimed that
      CD31 is distributed evenly over the entire endothelial cell surface. We re
      investigated this question with two different murine anti-CD31 antibodies (MEC
      13.3 and M-20), using a pre-embedding immunonanogold electron microscopic
      procedure that allowed precise label quantitation. MEC 13.3 reacted strongly with
      the luminal and abluminal plasma membranes of the endothelial cells lining
      microvessels in normal tissues and in angiogenic vessels induced by a tumor and
      vascular endothelial growth factor (VEGF-A164). Lateral plasma membranes were
      significantly less labeled. Conversely, M-20 strongly labeled the cytoplasmic
      face of the lateral plasma membranes of endothelial cells, although sparing
      specialized junctions, and only weakly labeled the luminal and abluminal plasma
      membranes. Both antibodies stained a significant minority of vesicles and
      vacuoles comprising the vesiculovacuolar organelle (VVO). Neither antibody was
      reactive in CD31-null mice. We conclude that CD31 is distributed over the entire
      endothelial cell surface, exclusive of specialized junctions, and in VVOs, but is
      not equally accessible to different antibodies in all locations.

PMID- 14688221
TI  - Immunolocalization of BMP-2/-4, FGF-4, and WNT10b in the developing mouse first
      lower molar.
AB  - Intercellular signaling controls all steps of odontogenesis. The purpose of this
      work was to immunolocalize in the developing mouse molar four molecules that play
      major roles during odontogenesis: BMP-2, -4, FGF-4, and WNT10b. BMP-2 and BMP-4
      were detected in the epithelium and mesenchyme at the bud stage. Staining for BMP
      2 markedly increased at the cap stage. The relative amount of BMP-4 strongly
      increased from E14 to E15. At E15, BMP-4 was detected in the internal part of the
      enamel knot where apoptosis was intense. In contrast to TGFbeta1, BMP-2 and -4
      did not show accumulation at the epithelial-mesenchymal junction where the
      odontoblast started differentiation. When odontoblasts became functional, BMP-2
      and BMP-4 were detected at the apical and basal poles of preameloblasts. BMP-2,
      which induces ameloblast differentiation in vitro, may also be involved
      physiologically. The decrease in FGF-4 from E14 to E15 supports a possible role
      for the growth factor in the control of mesenchymal cell proliferation. The
      relative amount of FGF-4 was maximal at E17. The subsequent decrease at E19
      showed correlation with the withdrawal of odontoblasts and ameloblasts from the
      cell cycle. WNT10b might also stimulate cell proliferation. At E14-15, WNT10b was
      present in the mesenchyme and epithelium except for the enamel knot, where the
      mitotic activity was very low. At E19 there was a decreasing gradient of staining
      from the cervical loop where cells divide to the tip of the cusp in the inner
      dental epithelium where cells become postmitotic. The target cells for FGF-4 and
      WNT10b appeared different.

PMID- 14688222
TI  - Tissue distribution of placental leucine aminopeptidase/oxytocinase during mouse
      pregnancy.
AB  - Placental leucine aminopeptidase (P-LAP), also called oxytocinase, is an enzyme
      responsible for hydrolyzing oxytocin. This enzyme is identical to cystine
      aminopeptidase. We examined the tissue distribution of P-LAP in normal adult mice
      and also in mothers and fetuses during mouse pregnancy using immunohistochemical
      (IHC) analysis. P-LAP-immunoreactive protein was expressed in various organs in a
      cell- and gestational stage-dependent manner. In the kidney, P-LAP was located in
      distal and collecting tubules but not in proximal tubules. The islet of
      Langerhans in the maternal pancreas stained positively for P-LAP in the periphery
      in early gestation. This staining pattern changed so that both the periphery and
      inner cells were positive during mid-gestation and finally only inner cells were
      positive in late gestation. Among the hematopoietic cells in the fetal liver,
      only megakaryocytes showed strong expression of P-LAP. The staining intensity
      increased with gestation on the apical surface of trophoblasts in the placental
      labyrinth. These data demonstrate that P-LAP is present in a variety of tissues,
      and its presence is affected by pregnancy and fetal development. Therefore, P-LAP
      may play a significant role in various physiological processes in non-pregnant,
      pregnant, and fetal mice.

PMID- 14688223
TI  - Distribution of substance P receptor (neurokinin-1 receptor) in normal ovine lung
      and during the progression of bronchopneumonia in sheep.
AB  - Substance P contributes to the physiological homeostasis of pulmonary airways and
      vasculature. During pneumonia, alterations in substance P production and receptor
      expression can influence bronchoconstriction and vascular perfusion. The
      distribution of substance P receptor [neurokinin-1 receptor (NK-1R)] in lungs of
      normal sheep and sheep with acute (1 day), subacute (15 days), and chronic (45
      days) bronchopneumonia caused by Mannheimia haemolytica was determined by
      immunohistochemistry (IHC). Three rabbit polyclonal antibodies generated to the
      same cytosolic C-terminal portion of NK-1R (residues 393-407) were tested. NK-1R
      immunoreactivity was traced in digital images and quantified with IPLAB software.
      There were no significant differences in NK-1R protein density between normal and
      infected lambs. Antibody 1 had the broadest distribution and intensity, and
      stained alveolar septae, smooth muscle cells of airways and vessels, epithelial
      cells of airways and alveoli, and submucosal glands. When all animals from the
      study were included, there was a trend towards decreased NK-1R immunoreactivity
      over time. The work suggests that (a) the density of NK-1R does not change during
      progression of bacterial (M. haemolytica) bronchopneumonia, (b) NK-1R is widely
      distributed in ovine lung and decreases with age, and (c) antibodies to the same
      NK-1R cytosolic region can vary in specificity and affinity.

PMID- 14688224
TI  - Phenotypic changes in dentition of Runx2 homozygote-null mutant mice.
AB  - Genetic and molecular studies in humans and mice indicate that Runx2 (Cbfa1) is a
      critical transcriptional regulator of bone and tooth formation. Heterozygous
      mutations in Runx2 cause cleidocranial dysplasia (CCD), an inherited disorder in
      humans and mice characterized by skeletal defects, supernumerary teeth, and
      delayed eruption. Mice lacking the Runx2 gene die at birth and lack bone and
      tooth development. Our extended phenotypic studies of Runx2 mutants showed that
      developing teeth fail to advance beyond the bud stage and that mandibular molar
      organs were more severely affected than maxillary molar organs. Runx2 (-/-) tooth
      organs, when transplanted beneath the kidney capsules of nude mice, failed to
      progress in development. Tooth epithelial-mesenchymal recombinations using Runx2
      (+/+) and (-/-) tissues indicate that the defect in mesenchyme cannot be rescued
      by normal dental epithelium. Finally, our molecular analyses showed differential
      effects of the absence of Runx2 on tooth extracellular matrix (ECM) gene
      expression. These data support the hypothesis that Runx2 is one of the key
      mesenchymal factors that influences tooth morphogenesis and the subsequent
      differentiation of ameloblasts and odontoblasts.

PMID- 14688225
TI  - Post-embedding double-labeling of antigen-retrieved ultrathin sections using a
      silver enhancement-controlled sequential immunogold (SECSI) technique.
AB  - In electron microscopy, the post-embedding immunogold technique provides a high
      degree of resolution and the possibility of quantitation owing to the intrinsic
      characteristics of the colloidal gold marker. Application of this technique to
      the subcellular localization of multiple antigens by differential labeling using
      gold markers of different sizes, or to double labeling using the same primary
      antibody isotype with serial silver enhancement, has been reported. We have
      incorporated this double labeling technique into a modified procedure that
      produces excellent labeling and ultrastructural preservation, even after exposure
      of ultrathin sections large enough to cover a 300- micro m-diameter single-hole
      grid to hot antigen retrieval solutions and prolonged labeling protocols.

PMID- 14688226
TI  - Breaking cellular symmetry along planar axes in Drosophila and vertebrates.
AB  - In many organs, epithelial cells are polarized not only along the apicobasal
      axis, but also along a second axis within a plane. Acquisition of the latter
      polarity, known as planar cell polarity (PCP) or tissue polarity, is crucial for
      specialized cellular functions. Genetic programming of PCP has been most
      thoroughly studied in Drosophila, which has allowed identification of a number of
      regulatory molecules that are evolutionally conserved. One group of the
      regulators is responsible for interpreting a hypothetical polarity cue and
      directing local cytoskeletal reorganization. This group includes a seven-pass
      transmembrane cadherin known as Flamingo (also known as Starry night), other
      receptors, and downstream components; and many of those molecules are
      redistributed to restricted subcellular compartments. Recent studies on a trio of
      cell-surface molecules challenge a previous hypothesis about the identity of the
      polarity cue and prompt a novel hypothesis about a global input. Studies on
      vertebrate systems support the notion that the molecular mechanisms demonstrated
      in Drosophila are applicable to at least two classes of polarized behaviors of
      vertebrate cells: sensory hair morphogenesis in the inner ear epithelium, and
      convergent extension movements during gastrulation.

PMID- 14688227
TI  - Roles of the intercellular adhesion molecule nectin in intracellular signaling.
AB  - The nectin family comprises four Ca(2+)-independent immunoglobulin-like cell-cell
      adhesion molecules. Each nectin homophilically and heterophilically trans
      interacts and causes intercellular adhesion, which organizes a variety of
      intercellular junctions in cooperation with, or independently of, cadherin.
      Nectin furthermore induces activation of Cdc42 and Rac small G proteins through c
      Src, which eventually regulates formation of the cadherin-based adherens
      junctions through reorganization of the actin cytoskeleton, gene expression
      through activation of a mitogen-activated protein kinase cascade, and cell
      polarization through cell polarity proteins. We describe here the roles of nectin
      in intracellular signaling.

PMID- 14688228
TI  - Role of the zinc fingers of HIV-1 nucleocapsid protein in maturation of genomic
      RNA.
AB  - The nucleocapsid protein of HIV-1 consists of two basic amino acid regions and
      two zinc fingers. We investigated the requirement of these domains for the
      structural conversion of a 39mer RNA covering the dimerization initiation site by
      using three peptides; wild-type NCp7, a mutant in which the two zinc fingers are
      mutated, and another mutant in which the two zinc fingers are deleted. The two
      mutants exhibited similar conversion activities to each other, which were lower
      than that of the wild-type, indicating that the two basic regions exhibit some
      activity for RNA chaperone, as we suggested before, and the zinc fingers enhance
      the efficiency of this activity.

PMID- 14688229
TI  - In vivo modification of the UDP-glucuronosyltransferase functional state in rat
      liver following hypophysectomy and partial or complete hormonal restoration.
AB  - The effects of growth hormone on the uridine diphosphate glucuronosyltransferase
      functional state, biophysical membrane parameters (order parameters and
      rotational correlation frequency) and the composition in phospholipids were
      studied in male rat hepatic microsomes. Sham-operated and hypophysectomized
      animals were injected with two different dosages of growth hormone, mimicking
      either the male or female growth hormone secretion pattern. Half the animals
      received thyroxine and cortisol in concentrations chosen to compensate for the
      lack of thyroid hormones and glucocorticoids in hypophysectomized rats. Growth
      hormone treatment resulted in a decrease in the latency (that gives a
      quantification of uridine diphosphate glucuronosyltransferase functional state)
      of the glucuronidation activities towards various substrates (testosterone,
      androsterone, bilirubin and 4-nitrophenol). This decrease with growth hormone
      treatment was particularly evident in hypophysectomized animals that had received
      cortisol and thyroxine supplementation treatment. These modifications were
      strongly correlated with modifications in the microsomal membrane
      lysophospholipid content and to a lower extent with microsomal membrane fatty
      acid composition. The cytosolic phospholipase A(2)-dependent increase in the
      lysophospholipid content in the endoplasmic reticulum is probably a major
      determinant in the regulation of the functional state of glucuronoyltransferases
      in response to high dosage growth hormone treatment.

PMID- 14688230
TI  - Purification and characterization of YfkN, a trifunctional nucleotide
      phosphoesterase secreted by Bacillus subtilis.
AB  - YfkN isolated from the culture supernatant of Bacillus subtilis in the
      exponential phase of growth is a protein of 143.5 kDa that derives from a
      putative large precursor of 159.6 kDa processed at both the N- and C-terminal
      ends. Pulse-chase experiments indicated that the release occurs slowly with a
      half-time longer than 30 min, suggesting that the event is coupled with wall
      turnover. YfkN exhibits 2',3' cyclic nucleotide phosphodiesterase, 2' (or 3')
      nucleotidase and 5' nucleotidase activities. In vitro the protein is reduced by
      subtilisin digestion to a shorter polypeptide (68 kDa), displaying
      phosphodiesterase activity but devoid of any 5'nucleotidase activity. This
      proteolytic processing led us to localize the potential active sites of the
      various nucleotidase activities. When bacteria were grown in low phosphate
      medium, the exocellular production of the enzyme was enhanced, suggesting that it
      plays a role in phosphate metabolism. Comparison with nucleotidase databases
      suggests that yfkN resulted from gene fusion.

PMID- 14688231
TI  - Intermolecular contact regions in urokinase plasminogen activator receptor.
AB  - The glycolipid-anchored urokinase-type plasminogen activator receptor (uPAR) is
      engaged in various signal transduction events related to cell adhesion, migration
      and proliferation. In this study, using phage display and peptide array
      techniques, we have identified several intermolecular contact regions of uPAR.
      Phage-displayed uPAR fragments bound to immobilized soluble uPAR on magnetic
      beads, revealing that regions uPAR-(7-28) and uPAR-(60-91) in domain I, uPAR-(101
      121) in domain II and uPAR-(240-260) in domain III are possible uPAR-uPAR contact
      sites. Using peptide array, two additional sites could be identified, uPAR-(51
      59) in domain I and uPAR-(144-155) in domain II. The putative uPAR-uPAR
      interaction sites are different from the previously identified uPA-binding sites.
      Functionally, peptides uPAR-(84-95) and uPAR-(240-248) could partially inhibit
      differentiated human U937 monocyte adhesion to vitronectin in the presence of
      uPA, indicating that these two uPAR regions might be involved not only in uPAR
      uPAR but also in uPAR-vitronectin interactions. We propose that multiple uPAR
      uPAR ectodomain interactions contribute considerably to the regulation of various
      cellular functions of uPAR.

PMID- 14688232
TI  - Truncation of the N-terminal ectodomain has implications in the N-glycosylation
      and transport to the cell surface of Edg-1/S1P1 receptor.
AB  - The endothelial cell-expressed sphingosine 1-phosphate receptors Edg-1/S1P1 and
      Edg-3/S1P3 have been implicated in various physiological events such as the
      regulation of angiogenesis. Since there is an excess of a ligand constitutively
      in blood, these receptors may have some mechanism(s) avoiding overstimulation. In
      this study, we found that the N-terminal ectodomains of Edg-1/S1P1 and Edg-3/S1P3
      were truncated in overexpressing cells. The truncated form of Edg-1/S1P1
      expressed on the cell surface had undergone complex-type oligosaccharide
      modification at the Golgi. A deletion mutant lacking the N-terminal processing
      domain of Edg-1/S1P1 accumulated in the endoplasmic reticulum, and was not
      expressed on the cell surface. When a basic amino acid residue was introduced at
      the cleavage site of Edg-1/S1P1, the molecular weight of the glycosylated protein
      was greater in the mutant compared to the wild type, due to the bound
      oligosaccharide. These results demonstrated that the structure of the N-terminal
      ectodomain of Edg-1/S1P1 affects both its transport to the cell surface and the N
      glycosylation process. Ectodomain shedding of many membrane proteins has been
      implicated in various diseases. Therefore, N-terminal processing of Edg-1/S1P1
      and Edg-3/S1P3 might play roles in endothelial cell functions.

PMID- 14688233
TI  - Molecular cloning of the human beta1,4 N-acetylgalactosaminyltransferase
      responsible for the biosynthesis of the Sd(a) histo-blood group antigen: the
      sequence predicts a very long cytoplasmic domain.
AB  - The Sd(a) antigen is a carbohydrate determinant expressed on erythrocytes, the
      colonic mucosa and other tissues. This epitope, whose structure is
      Siaalpha2,3[GalNAcbeta1,4]Gal beta1,4GlcNAc, is synthesized by a beta1,4 N
      acetylgalactosaminyltransferase (beta4GalNAc-T) that transfers a beta1,4-linked
      GalNAc to the galactose residue of an alpha2,3-sialylated chain. We have cloned
      from human colon carcinoma Caco2 cells a cDNA whose transfection in COS cells
      induces a GalNAc-T active on sialylated but not on asialylated fetuin and
      putatively represents the human Sd(a) beta4GalNAc-T. The cDNA predicts a 566 aa
      protein showing 66.6% and 39% identity with mouse CT beta4GalNAc-T and human
      GM2/GD2 synthase, respectively, with a typical type II glycosyltransferase
      organization, no potential N-glycosylation sites and a 67 aa cytoplasmic tail,
      which is probably the longest among the glycosyltransferases cloned to date. The
      gene maps in chromosome 17q23, and is composed of at least 11 exons. Exons 2-11
      are homologous to exons 2-11 of the previously cloned CT beta4GalNAc-T from
      murine cytotoxic T lymphocytes while exons 1 of the two enzymes are totally
      different. The mRNA is expressed at a high level in differentiated Caco2 cells
      and in colonic mucosa and at a much lower level in lymphocytes and other colon
      cancer cell lines.

PMID- 14688234
TI  - Effect of nitration on the activity of bovine erythrocyte Cu,Zn-superoxide
      dismutase (BESOD) and a kinetic analysis of its dimerization-dissociation
      reaction as examined by subunit exchange between the native and nitrated BESODs.
AB  - Bovine erythrocyte Cu,Zn-superoxide dismutase (BESOD) is a dimeric enzyme
      composed of identical subunits associated through unusually strong non-covalent
      interactions. The state of the unique tyrosyl residue (Tyr 108) of BESOD was
      examined, and the kinetics of subunit exchange was studied using Tyr 108 as a
      probe. UV-absorption difference spectra demonstrate that Tyr 108 is exposed to
      the solvent, and that the accessibilities to ethanol, ethylene glycol, and
      polyethylene glycol 600 are 53.5, 52.0, and 44.6%, respectively. Tyr 108 was
      fully nitrated by tetranitromethane. The pK(a) values of the phenolic hydroxyl
      group of native and nitrated Tyr 108 were determined to be 11.3 and 7.9, whereas
      those of model compounds, L-tyrosine and 3-nitro-L-tyrosine, are 9.8 and 6.8,
      respectively. When the native and nitrated BESODs of an equal concentration were
      mixed, the hybrid dimer was formed. From the amount of hybrid dimer formed, the
      rate constant (k(-1)) of the subunit dissociation at pH 7.8, 25 degrees C was
      assessed to be (4.17 +/- 0.13) x 10(-6) s(-1). The activation energy of the
      subunit dissociation at pH 7.8 was determined to be 117 +/- 4 kJ.mol(-1). The k(
      1) value remains constant at BESOD concentrations ranging from 0.62 to 6.8 micro
      M and at pH ranging from 6.0 to 10.0, but increased remarkably with a decrease in
      the dielectric constant of the reaction mixture. It is suggested that hydrophobic
      interaction may play a significant role in the subunit interaction.

PMID- 14688235
TI  - Inhibition of Bacillus subtilis aprE expression by lincomycin at the
      posttranscriptional level through inhibition of ppGpp synthesis.
AB  - Expression of the Bacillus subtilis alkaline protease gene aprE is controlled by
      many positive and negative regulators at the transcriptional level. During the
      course of screening for organic compounds that affect the expression of a
      translational aprE'-'lacZ fusion, we found that lincomycin (Lm), erythromycin and
      chloramphenicol exhibited an inhibitory effect in concentrations that hardly
      affected cell growth. The antibiotics are known to inhibit protein synthesis by
      binding to ribosomes. We chose one of them, Lm, for further study. We have
      previously shown that aprE expression requires guanosine 3',5'-bisdiphosphate
      (ppGpp) synthesized on the ribosome by the stringent factor RelA. An examination
      of Lm-treated cells showed that the levels of ppGpp were greatly reduced in these
      cells, and the inhibitory effect of the antibiotic was not seen in relA
      disruption mutants. Transcriptional levels of aprE, however, were not influenced
      by Lm treatment as shown by using a transcriptional aprE-lacZ fusion as well as
      quantitative RT-PCR. Furthermore, disruption of relA did not affect the
      expression of transcriptional aprE-lacZ. From these results, we conclude that
      aprE expression is controlled by the stringent control at the posttranscriptional
      level, and that Lm inhibits this process by inhibiting ppGpp synthesis on the
      ribosome.

PMID- 14688236
TI  - Induction of PYPAF1 during in vitro maturation of mouse mast cells.
AB  - Coculture of mouse bone marrow-derived immature mast cells (BMMC) with Swiss 3T3
      fibroblasts in the presence of stem cell factor (SCF) promotes morphological and
      functional maturation toward a connective tissue mast cell (CTMC)-like phenotype,
      which is accompanied by increased expression of several unique genes. Here we
      report the molecular identification of one of them, mast cell maturation
      associated inducible gene (MMIG)-1. The MMIG-1 cDNA encodes a 117-kDa cytosolic
      protein that comprises an N-terminal PYRIN domain, a central nucleotide-binding
      domain, and nine C-terminal leucine-rich repeats. MMIG-1 shows >85% sequence
      similarity to human cryopyrin/PYPAF1, a causal gene for familial cold urticaria
      and Muckle-Wells syndrome. MMIG-1 was distributed in the cytosol of CTMC-like
      differentiated BMMC. MMIG-1 underwent alternative splicing in the leucine-rich
      repeats and each variant was induced differently in BMMC during coculture.
      Moreover, its expression was increased in the ears of mice with experimental
      atopic dermatitis. Thus, MMIG-1, a likely mouse PYPAF1 ortholog, may play a role
      in mast cell-directed inflammatory diseases.

PMID- 14688237
TI  - Molecular, biochemical and immunological analyses of canine pancreatic DNase I.
AB  - The DNase I from canine pancreas was purified 260-fold to electrophoretic
      homogeneity with a 35% yield using three-step column chromatography. The activity
      of the purified enzyme was completely inhibited by 20 mM EDTA, an antibody
      specific to the purified enzyme and G-actin. A 1,373-bp cDNA encoding canine
      DNase I was constructed from the total canine pancreatic RNA using a rapid
      amplification of cDNA ends method, followed by sequencing. The mature canine
      DNase I protein was found to consist of 262 amino acids. A survey of DNase I in
      13 different canine tissues revealed the highest levels of both DNase I enzyme
      activity and gene expression in the pancreas; therefore, the canine DNase I is of
      the pancreatic type. Phylogenetic and sequence identity analyses, studies of
      immunological properties and the tissue-distribution patterns of DNase I
      indicated that the canine enzyme is more closely related to the human DNase I
      than to other mammalian DNases I. Therefore, canine DNase I is found to be one of
      the best substitutes in studies of human DNase I.

PMID- 14688238
TI  - Purification of electron-transferring flavoprotein from Megasphaera elsdenii and
      binding of additional FAD with an unusual absorption spectrum.
AB  - Electron-transferring flavoprotein (ETF), its redox partner flavoproteins, i.e.,
      D-lactate dehydrogenase and butyryl-CoA dehydrogenase, and another well-known
      flavoprotein, flavodoxin, were purified from the same starting cell paste of an
      anaerobic bacterium, Megasphaera elsdenii. The purified ETF contained one mol
      FAD/mol ETF as the sole non-protein component and bound almost one mol of
      additional FAD. This preparation is a better subject for investigations of M.
      elsdenii ETF than the previously isolated ETF, which contains varying amounts of
      FAD and varying percentages of modified flavins such as 6-OH-FAD and 8-OH-FAD.
      The additionally bound FAD shows an anomalous absorption spectrum with strong
      absorption around 400 nm. This spectral change is not due to a chemical
      modification of the flavin ring because the flavin released by KBr or guanidine
      hydrochloride is normal FAD. It is also not due to unknown small molecules
      because the same spectrum appears when ETF is reconstituted from its guanidine
      denatured subunits and FAD. A similar anomalous spectrum was observed for AMP
      free pig ETF under acidic conditions, suggesting a common flavin environment
      between pig and M. elsdenii ETFs.

PMID- 14688239
TI  - Interaction between pyridoxal kinase and pyridoxal-5-phosphate-dependent enzymes.
AB  - The interactions of two pyridoxal-5-phosphate (PLP)-dependent enzymes, alanine
      aminotransferase (ALT) and glutamate decarboxylase (GAD), with pyridoxal kinase
      (PK) were studied by fluorescence polarization as well as surface plasmon
      resonance techniques. The results demonstrated that PK can specifically bind to
      ALT and GAD. Moreover, binding profiles of both enzymes to immobilized PK were
      altered by excess amount of PLP. The equilibrium affinity constants for ALT in
      the absence and presence of PLP are 20.4 x 10(4) M(-1)and 6.7 x 10(4) M(-1), and
      for GAD are 37 x 10(4) M(-1)and 20.8 x 10(4) M(-1), respectively. It appears that
      specific interactions occur between PK and PLP-dependent enzymes, and the binding
      affinities of PK for PLP-dependent enzymes decrease in the presence of PLP. The
      results support our hypothesis that PLP transfer from PK to PLP-dependent enzymes
      requires a specific interaction between PK and the enzyme.

PMID- 14688240
TI  - A novel metalloprotease from Gloydius halys venom induces endothelial cell
      apoptosis through its protease and disintegrin-like domains.
AB  - A novel hemorrhagic metalloprotease, halysase, isolated from the snake venom of
      Gloydius halys induces apoptosis in endothelial cells. The purified
      metalloprotease is a monomeric glycoprotein with an isoelectric point of 4.8.
      Analysis of the cDNA sequence encoding halysase revealed that the enzyme consists
      of multifunctional domains including a proprotein domain, a protease domain, a
      disintegrin-like domain and a cysteine-rich domain. The metalloprotease has a
      DECD sequence in the disintegrin-like domain instead of the typical RGD sequence.
      Halysase strongly inhibits proliferation of human umbilical vein endothelial
      cells in a dose-dependent manner as well as adhesion of the cells to
      extracellular matrix proteins. The enzyme specifically hydrolyzes not only
      extracellular matrix proteins such as fibronectin, vitronectin, and type IV
      collagen, but also integrins alpha1beta1 and alpha5beta1. The apoptosis of
      endothelial cells induced by halysase is closely associated with activation of
      caspase-3 and decreased level of Bcl-X(L)/Bax. Apohalysase, which lacks
      metalloprotease activity, is also able to induce the apoptosis. Several lines of
      experimental evidence suggest that the protease domain and the disintegrin-like
      domain of halysase cooperatively contribute to the induction of endothelial cell
      apoptosis.

PMID- 14688241
TI  - Negamycin restores dystrophin expression in skeletal and cardiac muscles of mdx
      mice.
AB  - The ability of aminoglycoside antibiotics to promote read-through of nonsense
      mutations has attracted interest in these drugs as potential therapeutic agents
      in genetic diseases. However, the toxicity of aminoglycoside antibiotics may
      result in severe side effects during long-term treatment. In this paper, we
      report that negamycin, a dipeptide antibiotic, also restores dystrophin
      expression in skeletal and cardiac muscles of the mdx mouse, an animal model of
      Duchenne muscular dystrophy (DMD) with a nonsense mutation in the dystrophin
      gene, and in cultured mdx myotubes. Dystrophin expression was confirmed by
      immunohistochemistry and immunoblotting. We also compared the toxicity of
      negamycin and gentamicin, and found negamycin to be less toxic. Furthermore, we
      demonstrate that negamycin binds to a partial sequence of the eukaryotic rRNA
      decoding A-site. We conclude that negamycin is a promising new therapeutic
      candidate for DMD and other genetic diseases caused by nonsense mutations.

PMID- 14688242
TI  - Cellular requirements for CRM1 import and export.
AB  - We studied the cellular requirements for the translocation of CRM1 (exportin 1)
      between the nucleus and the cytoplasm. CRM1 import requires neither ATP, Ran, Ran
      dependent GTP hydrolysis, nor a particular temperature. CRM1 and importin beta
      compete with each other during their import. Thus, CRM1 is able to enter the
      nucleus in a manner similar to importinbeta. In contrast, the in vivo export of
      CRM1 involves ATP-consuming step(s).

PMID- 14688243
TI  - Polyamine homeostasis in transgenic plants overexpressing ornithine decarboxylase
      includes ornithine limitation.
AB  - It was reported recently that overexpression of human ornithine decarboxylase
      (ODC) cDNA in transgenic rice plants resulted in increased steady-state
      concentration of polyamines, i.e., enough biosynthetic control is invested at
      this step to enable adjustment of polyamine levels. To investigate critically
      whether constitutive overexpression of ODC is sufficient to control steady-state
      polyamine levels, we expressed an ODC cDNA from Datura stramonium in transgenic
      tobacco plants. Transgenic progeny of self-fertilised primary transformants
      exhibited increases in ODC activity of 25-fold in leaves and 5-fold in flower
      buds. However, the increase in putrescine levels was only 1.5- to 2.1-fold in
      leaves and 1.1- to 1.3-fold in flower buds. Emphatically, no changes to
      spermidine or spermine steady-state levels or to soluble or insoluble
      hydroxycinnamic acid-conjugated polyamines were observed. Ornithine feeding to
      cell suspension cultures derived from the transgenic plants indicated that
      putrescine accumulation was limited in part by ornithine availability. These
      results demonstrate that a large increase in the capacity of the tobacco plants
      to decarboxylate ornithine does not result in a comparable increase in the level
      of free or conjugated polyamines. Plant polyamine homeostatic mechanisms
      efficiently accommodate increased ODC activity, suggesting that polyamine
      biosynthetic control is invested at multiple interdependent steps.

PMID- 14688245
TI  - Tyrosine radical formation in the reaction of wild type and mutant cytochrome
      P450cam with peroxy acids: a multifrequency EPR study of intermediates on the
      millisecond time scale.
AB  - We report a multifrequency (9.6-, 94-, 190-, and 285-GHz) EPR study of a freeze
      quenched intermediate obtained from reaction of substrate-free cytochrome P450cam
      (CYP101) and its Y96F and Y96F/Y75F mutants with peroxy acids. It is generally
      assumed that in such a shunt reaction an intermediate [Fe(IV)=O, porphyrin-pi
      cation radical] is formed, which should be identical to the species in the
      natural reaction cycle. However, for the wild type as well as for the mutant
      proteins, a porphyrin-pi-cation radical is not detectable within 8 ms. Instead,
      EPR signals corresponding to tyrosine radicals are obtained for the wild type and
      the Y96F mutant. Replacement of both Tyr-96 and Tyr-75 by phenylalanine leads to
      the disappearance of the tyrosine EPR signals. EPR studies at 285 GHz on freeze
      quenched wild type and Y96F samples reveal g tensor components for the radical
      (stretched g(x) values from 2.0078 to 2.0064, g(y) = 2.0043, and g(z) = 2.0022),
      which are fingerprints for tyrosine radicals in a heterogeneous polar
      environment. The measurements at 94 GHz using a fundamental mode microwave
      resonator setup confirm the 285-GHz study. From the simulation of the hyperfine
      structure in the 94-GHz EPR spectra the signals have been assigned to Tyr-96 in
      the wild type and to Tyr-75 in the Y96F mutant. We suggest that a transiently
      formed Fe(IV)=O porphyrin-pi-cation radical intermediate in P450cam is reduced by
      intramolecular electron transfer from these tyrosines within 8 ms.

PMID- 14688246
TI  - Distal heme pocket conformers of carbonmonoxy derivatives of Ascaris hemoglobin:
      evidence of conformational trapping in porous sol-gel matrices.
AB  - We report the ligand dependence of the conformer distribution in the distal heme
      pocket of Ascaris suum hemoglobin (Hb) studied by resonance Raman spectroscopy.
      The heme-bound CO is used as a spectroscopic antenna to probe the original
      distribution of conformers in the dioxygen derivative of Ascaris Hb, by utilizing
      sol-gel encapsulation. The first step is to encapsulate the dioxygen derivative
      in the porous sol-gel and let the gel age, thus trapping the equilibrium
      conformational distribution of Ascaris dioxygen Hb. In the second step, the
      dioxygen ligand is replaced by CO. The sol-gel environment impedes any large
      scale movements, drastically slowing down the conformational relaxation triggered
      by the ligation change, essentially "locking in" the initial quaternary and even
      tertiary structure of the protein. Studying the Fe-CO frequencies of the latter
      sample allows evaluation of the distribution of the distal heme pocket conformers
      that was originally associated with the dioxygen derivative. Extending the study
      to the Ascaris mutants allows for examination of the effect of specific residues
      in the distal pocket on the conformational distribution. The choice of mutants
      was largely based on the anticipated variation in hydrogen bonding patterns. The
      results show that the sol-gel encapsulation can slow or prevent re-equilibration
      within the distal heme pocket of Ascaris Hb and that the distribution of distal
      heme pocket conformers for the CO derivative of Ascaris Hb in the sol-gel is
      highly dependent on the history of the sample. Additionally, we report a detailed
      study of the CO complex of the mutants in solution for assignment of the various
      heme pocket conformers, and we present a comparison of the sol-gel data with
      solution data. The results support a picture in which the dioxygen derivative
      biases the population strongly toward a tightly packed configuration that favors
      the network of strong hydrogen bonding interactions, and suggest that Ascaris Hb
      is uniquely designed for dioxygen capture.

PMID- 14688247
TI  - Effect of inhibiting vacuolar acidification on insulin signaling in hepatocytes.
AB  - Previous studies have shown that the endosomal apparatus plays an important role
      in insulin signaling. Inhibition of endosomal acidification leads to a decrease
      in insulin-insulin receptor kinase (IRK) dissociation and insulin degradation.
      Thus, vacuolar pH could function as a modulator of insulin signaling in
      endosomes. In the present study we show that in primary hepatocytes pretreated
      with bafilomycin, there is an inhibition of vacuolar acidification. Incubation of
      these cells with insulin was followed by an augmentation of IRK activity but an
      inhibition of phosphatidylinositol 3-kinase/Akt activity and a decrease in
      insulin-induced DNA and glycogen synthesis. Bafilomycin treatment inhibited IRK
      recycling to the plasma membrane without affecting IRK internalization. Impaired
      IRK recycling correlated with a decrease in insulin signaling. We suggest that
      inhibiting vacuolar acidification sequesters activated IRKs in an intracellular
      compartment(s) where signaling is inhibited. This implies that endosomal receptor
      trafficking plays a role in regulating signal transduction.

PMID- 14688248
TI  - Dissecting the broad substrate specificity of human 3-methyladenine-DNA
      glycosylase.
AB  - Human alkyladenine-DNA glycosylase (AAG) catalyzes the excision of a broad range
      of modified bases, protecting the genome from many types of alkylative and
      oxidative DNA damage. We have investigated how AAG discriminates against normal
      DNA bases, while accommodating a structurally diverse set of lesioned bases, by
      measuring the rates of AAG-catalyzed (k(st)) and spontaneous N-glycosidic bond
      hydrolysis (k(non)) for damaged and undamaged DNA oligonucleotides. The rate
      enhancements for excision of different bases reveal that AAG is most adept at
      excising the deaminated lesion hypoxanthine (k(st)/k(non) = 10(8)), suggesting
      that enzymatic activity may have evolved in response to this lesion. Comparisons
      of the rate enhancements for excision of normal and modified purine nucleobases
      provide evidence that AAG excludes the normal purines via steric clashes with the
      exocyclic amino groups of adenine and guanine. However, methylated purines are
      more chemically labile, and only modest rate enhancements are required for their
      efficient excision. Base flipping also contributes to specificity as destabilized
      mismatched base pairs are better substrates than stable Watson-Crick pairs, and
      many of the lesions recognized by AAG are compromised in their ability to base
      pair. These findings suggest that AAG reconciles a broad substrate tolerance with
      the biological imperative to avoid normal DNA by excluding normal bases from the
      active site rather than by specifically recognizing each lesion.

PMID- 14688249
TI  - S Phase-specific transcription of the mouse ribonucleotide reductase R2 gene
      requires both a proximal repressive E2F-binding site and an upstream promoter
      activating region.
AB  - Ribonucleotide reductase is essential for supplying a balanced pool of the four
      deoxyribonucleotides required for DNA synthesis and repair. The active enzyme
      consists of two non-identical subunits called proteins R1 and R2. There are
      multiple levels of regulation of ribonucleotide reductase activity, which is
      highest during the S and G(2) phases of an unperturbed cell cycle in mammalian
      cells. Previous reports in the literature have indicated that the S phase
      specific transcription of the mammalian R2 gene is regulated by a transcriptional
      block, is dependent on the transcription factor E2F1, or is simply regulated by
      proteins that bind to promoter CCAAT boxes plus the TATA box. Here, we
      demonstrate that the S phase-specific transcription of the mouse R2 gene is
      dependent on an upstream promoter activating region (located at nucleotides (nt) 
      672 to -527 from the transcription start site) and one proximal promoter
      repressive element (located at nt -112 to -107) that binds E2F4. Binding to the
      E2F site is modulated by binding of nuclear factor-Y to an adjacent CCAAT element
      (nt -79 to -75). The upstream activating region is crucial for overall R2
      promoter activity. Mutation of the E2F-binding site leads to premature promoter
      activation in G(1) and increases overall promoter activity but only when the
      upstream activating region is present and intact. Therefore, E2F-dependent
      repression is essential for cell cycle-specific R2 transcription.

PMID- 14688250
TI  - Myospryn is a novel binding partner for dysbindin in muscle.
AB  - Dysbindin is a coiled-coil-containing protein that was initially identified in a
      screen for dystrobrevin-interacting proteins. Recently, dysbindin has been shown
      to be involved in the biogenesis of lysosome-related organelles and is also a
      major schizophrenia susceptibility factor. Although dysbindin has been implicated
      in a number of different cellular processes, little is known about its function.
      To determine the function of dysbindin in muscle, we performed a yeast two-hybrid
      screen to identify potential interacting proteins. Here we show that dysbindin
      binds to a novel 413-kDa protein, myospryn, which is expressed in cardiac and
      skeletal muscle. The transcript encoding myospryn encompasses genethonin-3, a
      transcript that is down-regulated in muscle from Duchenne muscular dystrophy
      patients and stretch-responsive protein 553, which is up-regulated in
      experimental muscle hypertrophy. The C terminus of myospryn contains BBC, FN3,
      and SPRY domains in a configuration reminiscent of the tripartite motif protein
      family, as well as the dysbindin-binding site and a region mediating self
      association. Dysbindin and myospryn co-immunoprecipitate from muscle extracts and
      are extensively co-localized. These data demonstrate for the first time that
      there are tissue-specific ligands for dysbindin that may play important roles in
      the different disease states involving this protein.

PMID- 14688251
TI  - A glutamate is the essential proton transfer gate during the catalytic cycle of
      the [NiFe] hydrogenase.
AB  - Kinetic, EPR, and Fourier transform infrared spectroscopic analysis of
      Desulfovibrio fructosovorans [NiFe] hydrogenase mutants targeted to Glu-25
      indicated that this amino acid participates in proton transfer between the active
      site and the protein surface during the catalytic cycle. Replacement of that
      glutamic residue by a glutamine did not modify the spectroscopic properties of
      the enzyme but cancelled the catalytic activity except the para-H(2)/ortho-H(2)
      conversion. This mutation impaired the fast proton transfer from the active site
      that allows high turnover numbers for the oxidation of hydrogen. Replacement of
      the glutamic residue by the shorter aspartic acid slowed down this proton
      transfer, causing a significant decrease of H(2) oxidation and hydrogen isotope
      exchange activities, but did not change the para-H(2)/ortho-H(2) conversion
      activity. The spectroscopic properties of this mutant were totally different,
      especially in the reduced state in which a non-photosensitive nickel EPR spectrum
      was obtained.

PMID- 14688252
TI  - The j-subunit of human translation initiation factor eIF3 is required for the
      stable binding of eIF3 and its subcomplexes to 40 S ribosomal subunits in vitro.
AB  - Eukaryotic initiation factor 3 (eIF3) is a 12-subunit protein complex that plays
      a central role in binding of initiator methionyl-tRNA and mRNA to the 40 S
      ribosomal subunit to form the 40 S initiation complex. The molecular mechanisms
      by which eIF3 exerts these functions are poorly understood. To learn more about
      the structure and function of eIF3 we have expressed and purified individual
      human eIF3 subunits or complexes of eIF3 subunits using baculovirus-infected Sf9
      cells. The results indicate that the subunits of human eIF3 that have homologs in
      Saccharomyces cerevisiae form subcomplexes that reflect the subunit interactions
      seen in the yeast eIF3 core complex. In addition, we have used an in vitro 40 S
      ribosomal subunit binding assay to investigate subunit requirements for efficient
      association of the eIF3 subcomplexes to the 40 S ribosomal subunit. eIF3j alone
      binds to the 40 S ribosomal subunit, and its presence is required for stable 40 S
      binding of an eIF3bgi subcomplex. Furthermore, purified eIF3 lacking eIF3j binds
      40 S ribosomal subunits weakly, but binds tightly when eIF3j is added. Cleavage
      of a 16-residue C-terminal peptide from eIF3j by caspase-3 significantly reduces
      the affinity of eIF3j for the 40 S ribosomal subunit, and the cleaved form
      provides substantially less stabilization of purified eIF3-40S complexes. These
      results indicate that eIF3j, and especially its C terminus, play an important
      role in the recruitment of eIF3 to the 40 S ribosomal subunit.

PMID- 14688253
TI  - Intraluminal pressure is a stimulus for NFATc3 nuclear accumulation: role of
      calcium, endothelium-derived nitric oxide, and cGMP-dependent protein kinase.
AB  - The transcription factor NFAT (nuclear factor of activated T-cells) is implicated
      in cardiac hypertrophy and vasculogenesis. NFAT activation, reflecting
      dephosphorylation by the calcium-dependent phosphatase, calcineurin, and
      subsequent nuclear localization, is generally thought to require a sustained
      increase in intracellular calcium. However, in smooth muscle we have found that
      elevation of calcium by membrane depolarization fails to induce an increase in
      nuclear localization of the NFATc3 isoform. Here, we demonstrate that
      physiological intravascular pressure (100 mm Hg) induces an increase in NFATc3
      nuclear localization in mouse cerebral arteries. Pressure-induced NFATc3 nuclear
      accumulation is abrogated by endothelial denudation and by nitric-oxide synthase,
      cGMP-dependent kinase (PKG), and voltage-dependent calcium channels inhibition.
      We further show that exogenous nitric oxide, in combination with an elevation in
      calcium, is an effective stimulus for NFATc3 nuclear accumulation. c-Jun terminal
      kinase 2 (JNK) activity, which has been shown to regulate NFATc3 nuclear export,
      is also reduced by pressure, an effect that is prevented by pretreatment with a
      PKG inhibitor. Consistent with this, pressure-induced NFATc3 nuclear accumulation
      is independent of PKG in arteries from JNK2(-/-) mice. Collectively, our results
      indicate that both activation of the NO/PKG pathway and elevation of smooth
      muscle calcium are required for NFATc3 nuclear accumulation and that PKG inhibits
      JNK2 to decrease NFAT nuclear export. Our findings suggest that at physiological
      intravascular pressures NFATc3 is localized to the nucleus in smooth muscle cells
      of intact arteries and indicate a novel and unexpected role for nitric oxide/PKG
      in NFAT activation.

PMID- 14688254
TI  - Repeat sequence of Epstein-Barr virus-encoded nuclear antigen 1 protein
      interrupts proteasome substrate processing.
AB  - The Epstein-Barr virus thwarts immune surveillance through a Gly-Ala repeat (GAr)
      within the viral Epstein-Barr virus-encoded nuclear antigen 1 protein. The GAr
      inhibits proteasome processing, an early step in antigen peptide presentation,
      but the mechanism of proteasome inhibition has been unclear. By embedding a GAr
      within ornithine decarboxylase, a natural proteasome substrate that does not
      require ubiquitin conjugation, we now demonstrate inhibition in a purified
      system, excluding involvement of ubiquitin conjugation or of proteins extraneous
      to substrate and proteasome. We show further that the GAr acts as a stop-transfer
      signal in proteasome substrate processing, resulting in vivo in partial
      proteolysis that halts just short of the GAr. Similarly, introducing a GAr into
      green fluorescent protein destabilized by the ornithine decarboxylase degradation
      domain also stops the progress of proteolysis, leading to the accumulation of
      partial degradation products. We postulate that the ATP motor of the proteasome
      slips when it encounters the GAr, impeding further insertion and, in this way,
      halting degradation.

PMID- 14688256
TI  - Potent anti-tumor effects of an active site mutant of human manganese-superoxide
      dismutase. Evolutionary conservation of product inhibition.
AB  - Mn-SOD serves as the primary cellular defense against oxidative damage by
      converting superoxide radicals (O(2)(-)) to O(2) and H(2)O(2). A unique
      characteristic of this mitochondrial anti-oxidant enzyme is the conservation from
      bacteria to man of a rapidly formed product inhibited state. Using site-directed
      mutagenesis, we have generated an active site mutant (H30N) of human Mn-SOD,
      which exhibits significantly reduced product inhibition and increased enzymatic
      efficiency. Overexpression of the H30N enzyme causes anti-proliferative effects
      in vitro and anti-tumor effects in vivo. Our results provide a teleological basis
      for the phylogenetically invariant nature of position His-30 and the evolutionary
      conservation of product inhibition. These data also provide more direct
      intracellular evidence for the signaling role associated with H(2)O(2).

PMID- 14688255
TI  - MAPKAP kinase 2 phosphorylates tristetraprolin on in vivo sites including Ser178,
      a site required for 14-3-3 binding.
AB  - MAPKAP kinase 2 (MK2) is required for tumor necrosis factor synthesis.
      Tristetraprolin (TTP) binds to the 3'-untranslated region of tumor necrosis
      factor mRNA and regulates its fate. We identified in vitro and in vivo
      phosphorylation sites in TTP using nanoflow high pressure liquid chromatography
      microelectrospray ionization tandem mass spectrometry and novel methods for
      direct digestion of TTP bound to affinity matrices (GSH-beads or anti-Myc linked
      to magnetic beads). MK2Delta3B, activated in Escherichia coli by p38alpha,
      phosphorylates TTP in vitro at major sites Ser(52) and Ser(178) (>10-fold in
      abundance) as well as at several minor sites that were detected after enriching
      for phosphopeptides with immobilized metal affinity chromatography. MK2
      phosphorylation of TTP creates a functional 14-3-3 binding site. In cells, TTP
      was phosphorylated at Ser(52), Ser(178), Thr(250), and Ser(316) and at SP sites
      in a cluster (Ser(80)/Ser(82)/Ser(85)). Anisomycin treatment of NIH 3T3 cells
      increased phosphorylation of Ser(52) and Ser(178). Overexpression of MK2 sufficed
      to increase phosphorylation of Ser(52) and Ser(178) but not
      Ser(80)/Ser(82)/Ser(85) or Thr(250). Thus, Ser(52) and Ser(178) are putative MK2
      sites in vivo. Identified phosphosite(s) may be biologic switches controlling
      mRNA stability and translation.

PMID- 14688257
TI  - Analysis of transmembrane segment 8 of the GLUT1 glucose transporter by cysteine
      scanning mutagenesis and substituted cysteine accessibility.
AB  - The GLUT1 glucose transporter has been proposed to form an aqueous substrate
      translocation pathway via the clustering of several amphipathic transmembrane
      helices (Mueckler, M., Caruso, C., Baldwin, S. A., Panico, M., Blench, I.,
      Morris, H. R., Allard, W. J., Lienhard, G. E., and Lodish, H. F. (1985) Science
      229, 941-945). The possible role of transmembrane helix 8 in the formation of
      this permeation pathway was investigated using cysteine-scanning mutagenesis and
      the membrane-impermeant sulfhydryl-specific reagent, p
      chloromercuribenzenesulfonate (pCMBS). Twenty-one GLUT1 mutants were created from
      a fully functional cysteine-less parental GLUT1 molecule by successively changing
      each residue along transmembrane segment 8 to a cysteine. The mutant proteins
      were then expressed in Xenopus oocytes, and their membrane concentrations, 2
      deoxyglucose uptake activities, and sensitivities to pCMBS were determined. Four
      positions within helix 8, alanine 309, threonine 310, serine 313, and glycine
      314, were accessible to pCMBS as judged by the inhibition of transport activity.
      All four of these residues are clustered along one face of a putative alpha
      helix. These results suggest that transmembrane segment 8 of GLUT1 forms part of
      the sugar permeation pathway. Updated two-dimensional models for the orientation
      of the 12 transmembrane helices and the conformation of the exofacial glucose
      binding site of GLUT1 are proposed that are consistent with existing experimental
      data and homology modeling based on the crystal structures of two bacterial
      membrane transporters.

PMID- 14688258
TI  - Activation of apoptosis signal-regulating kinase 1 by reactive oxygen species
      through dephosphorylation at serine 967 and 14-3-3 dissociation.
AB  - Oxidative stress has been indicated in a variety of pathological processes such
      as atherosclerosis, diabetes, and neurodegenerative diseases. Understanding how
      intracellular signaling pathways respond to oxidative insults such as hydrogen
      peroxide (H(2)O(2)) would have significant therapeutic implications. Recent
      genetic studies have placed apoptosis signal-regulating kinase 1 (ASK1) in a
      pivotal position in transmitting H(2)O(2)-initiated signals. How ASK1 is
      activated by H(2)O(2), though, remains a subject of intense investigation. Here
      we report a mechanism by which H(2)O(2) induces ASK1 activation through dynamic
      control of its phosphorylation at serine 967. We found that treatment of COS7
      cells with H(2)O(2) triggers dephosphorylation of Ser-967 through an okadaic acid
      sensitive phosphatase, resulting in dissociation of the ASK1.14-3-3 complex with
      concomitant increase of ASK1 catalytic activity and ASK1-mediated activation of
      JNK and p38 pathways.

PMID- 14688259
TI  - Transcription factors NF-YA regulate the induction of human OGG1 following DNA
      alkylating agent methylmethane sulfonate (MMS) treatment.
AB  - A human 8-oxoguanine-DNA glycosylase (hOGG1) is the main enzyme that repairs 8
      oxoG, which is a critical mutagenic lesion. There is a great deal of interest in
      the up- or down-regulation of OGG1 expression after DNA damage. In this study, we
      investigated the effect of a DNA-alkylating agent, methylmethane sulfonate (MMS),
      on hOGG1 expression level and found that MMS treatment resulted in an increase in
      the functional hOGG1 expression in HCT116 cells. A region between -121 and -61 of
      the hOGG1 promoter was found to be crucial for this induction by MMS. Site
      directed mutations of the two inverted CCAAT motifs substantially abrogated the
      induction of the hOGG1 promoter as a result of MMS treatment. In addition, the NF
      YA protein (binding to the inverted CCAAT box) was induced after exposing cells
      to MMS. Moreover, gel shift and supershift analyses with the nuclear extracts
      prepared from HCT116 cells identified NF-YA as the transcription factor
      interacting with the inverted CCAAT box. Mutations of the inverted CCAAT box
      either prevented the binding of this factor or abolished its activation as a
      result of MMS treatment. Finally, this study showed that hOGG1-expressing HCT116
      cells exhibited increased hOGG1 repair activity and resistance to MMS. Overall,
      these results demonstrate that MMS can up-regulate hOGG1 expression through the
      induction of the transcription factor, NF-YA, and increased transcription level
      of the hOGG1 gene correlates with an increase in enzyme activity providing
      functional protection from MMS.

PMID- 14688260
TI  - Hydrogen peroxide induces topoisomerase I-mediated DNA damage and cell death.
AB  - Reactive oxygen species modify DNA, generating various DNA lesions including
      modified bases such as 8-oxoguanine (8-oxoG). These base-modified DNA lesions
      have been shown to trap DNA topoisomerase I (TOP1) into covalent cleavage
      complexes. In this study, we have investigated the role of TOP1 in hydrogen
      peroxide toxicity. We showed that ectopic expression of TOP1 in Saccharomyces
      cerevisiae conferred sensitivity to hydrogen peroxide, and this sensitivity was
      dependent on RAD9 checkpoint function. Moreover, in the mammalian cell culture
      system, hydrogen peroxide-induced growth inhibition and apoptosis were shown to
      be partly TOP1-dependent as evidenced by a specific increase in resistance to
      hydrogen peroxide in TOP1-deficient P388/CPT45 murine leukemia cells as compared
      with their TOP1-proficient parental cell line P388. In addition, hydrogen
      peroxide was shown to induce TOP1-DNA cross-links. These results support a model
      in which hydrogen peroxide promotes the trapping of TOP1 on oxidative DNA lesions
      to form TOP1-DNA cleavage complexes that contribute to hydrogen peroxide
      toxicity.

PMID- 14688262
TI  - Ras protects Rb family null fibroblasts from cell death: a role for AP-1.
AB  - The retinoblastoma protein (Rb) controls cell proliferation, differentiation, and
      senescence and provides an essential tumor suppressive function that cells must
      eliminate to attain unlimited proliferative potential. Elimination of the Rb
      pathway also results in apoptosis, however, thereby providing an efficient
      surveillance mechanism to sense the loss of Rb. To become tumorigenic cells must
      thus overcome not only Rb function but also the apoptotic response caused by the
      loss of Rb function. We show that oncogenic Ras (RasV12) potently blocks cell
      death in Rb family member knockout mouse embryo fibroblasts (TKO cells).
      Activation of phosphatidylinositol 3-kinase and Raf by oncogenic Ras mediated
      this protection, implying that multiple Ras effector pathways are required, in
      concert, for this pro-survival signal. Although activation of Raf by selective
      Ras mutants protected TKO cells from cell death, pharmacologic inhibition of MEK
      had little effect on RasV12 protection, suggesting that a Raf-dependent, MEK
      independent pathway was important for this effect. We show that this Raf
      dependent protection occurred through activation of c-Jun and thus AP-1
      activation. These observations could account for the dependence of Ras
      transformation on c-Jun activity and for the roles of AP-1 in oncogenesis. Our
      results support the concept of two oncogenic events cooperating to achieve a
      balance between immortalization and survival.

PMID- 14688261
TI  - A novel pathway involving progesterone receptor, 12/15-lipoxygenase-derived
      eicosanoids, and peroxisome proliferator-activated receptor gamma regulates
      implantation in mice.
AB  - The 12/15-lipoxygenases (12/15-LOX) catalyze the stereo-specific oxygenation of
      arachidonic and linoleic acids into a complex series of signaling molecules,
      including the hydroxyeicosatetraenoic acids (HETEs) and hydroxyoctadecadienoic
      acids (HODEs). Our previous studies, using high density oligonucleotide
      microarrays, suggested a novel link between progesterone receptor (PR) signaling
      and 12/15-LOX-mediated fatty acid metabolism in preimplantation mouse uterus. In
      this paper, using PR knockout mice, we established that the transcripts encoding
      leukocyte-12/15-LOX (L-12/15-LOX) and epidermal-12/15-LOX (E-12/15-LOX) are
      indeed downstream targets of regulation by PR in the uterine surface epithelium.
      Maximal induction of both L- and E-12/15-LOX on the day of implantation resulted
      in a marked increase in the uterine levels of the eicosanoids, 12-HETE, 15-HETE,
      and 13-HODE. Mice with null mutation in L-12/15-LOX had significantly reduced
      uterine levels of arachidonic acid metabolites and exhibited a partial impairment
      in implantation. Complete blockade of uterine 12/15-LOX activity by a specific
      inhibitor led to greater than 80% reduction in a number of implantation sites
      relative to untreated controls. Cell-based assays indicated that 12-HETE, 15
      HETE, and 13-HODE function as activating ligands of peroxisome proliferator
      activated receptor gamma (PPARgamma), suggesting that this nuclear receptor could
      be a downstream target of 12/15-LOX-derived metabolites in the preimplantation
      uterus. Consistent with this hypothesis, administration of rosiglitazone, a
      potent PPARgamma-selective agonist, efficiently reversed inhibition of
      implantation by the 12/15-LOX-specific inhibitor. Rosiglitazone also induced a
      number of potential target genes of 12/15-LOX-derived metabolites in the pregnant
      uterus, indicating their regulation by PPARgamma. Collectively, our results
      uncovered a novel signaling pathway in which progesterone-induced synthesis of
      the 12/15-LOX-derived lipid mediators activates PPARgamma and its downstream gene
      networks, which in turn function as critical regulators of implantation in the
      mouse.

PMID- 14688263
TI  - TRIP6 enhances lysophosphatidic acid-induced cell migration by interacting with
      the lysophosphatidic acid 2 receptor.
AB  - Lysophosphatidic acid (LPA) induces actin rearrangement, focal adhesion assembly,
      and cell migration through the activation of small G protein Rho and its
      downstream effectors. These diverse cellular responses are mediated by its
      associated G protein-coupled receptors. However, the mechanisms and specificity
      by which these LPA receptors mediate LPA actions are still poorly understood.
      Here we show that LPA stimulation promotes the interaction of the LPA(2) receptor
      with a focal adhesion molecule, TRIP6 (thyroid receptor interacting protein
      6)/ZRP-1 (zyxin-related protein 1). TRIP6 directly binds to the carboxyl-terminal
      tail of the LPA(2) receptor through its LIM domains. LPA-dependent recruitment of
      TRIP6 to the plasma membrane promotes its targeting to focal adhesions and co
      localization with actin stress fibers. In addition, TRIP6 associates with the
      components of focal complexes including paxillin, focal adhesion kinase, c-Src,
      and p130(cas) in an agonist-dependent manner. Overexpression of TRIP6 augments
      LPA-induced cell migration; in contrast, suppression of endogenous TRIP6
      expression by a TRIP6-specific small interfering RNA reduces it in SKOV3 ovarian
      cancer cells. Strikingly, the association with TRIP6 is specific to the LPA(2)
      receptor but not LPA(1) or LPA(3) receptor, indicating a specific role for TRIP6
      in regulating LPA(2) receptor-mediated signaling. Taken together, our results
      suggest that TRIP6 functions at a point of convergence between the activated
      LPA(2) receptor and downstream signals involved in cell adhesion and migration.

PMID- 14688264
TI  - Tetramerization and ATP binding by a protein comprising the A, B, and C domains
      of rat synapsin I.
AB  - Synapsins are multidomain proteins that are critical for regulating
      neurotransmitter release in vertebrates. In the present study, two crystal
      structures of the C domain of rat synapsin I (rSynI-C) in complex with Ca(2+) and
      ATP reveal that this protein can form a tetramer and that a flexible loop (the
      "multifunctional loop") contacts bound ATP. Further experiments were carried out
      on a protein comprising the A, B, and C domains of rat synapsin I (rSynI-ABC). An
      ATP-stabilized tetramer of rSynI-ABC is observed during velocity sedimentation
      and size-exclusion chromatographic experiments. These hydrodynamic results also
      indicate that the A and B domains exist in an extended conformation. Calorimetric
      measurements of ATP binding to wild-type and mutant rSynI-ABC demonstrate that
      the multifunctional loop and a cross-tetramer contact are important for ATP
      binding. The evidence supports a view of synapsin I as an ATP-utilizing,
      tetrameric protein made up of monomers that have a flexible, extended N terminus.

PMID- 14688265
TI  - Iron-sulfur cluster biosynthesis: biochemical characterization of the
      conformational dynamics of Thermotoga maritima IscU and the relevance for
      cellular cluster assembly.
AB  - Important for the understanding of the functional properties of the iron-sulfur
      scaffold IscU is knowledge of the structure and dynamics of this protein class.
      Structural characterization of Thermotoga maritima IscU by CD (Mansy, S. S., Wu,
      G., Surerus, K. K., and Cowan, J. A. (2002) J. Biol. Chem. 277, 21397-21404) and
      high resolution NMR (Bertini, I., Cowan, J. A., Del Bianco, C., Luchinat, C., and
      Mansy, S. S. (2003) J. Mol. Biol. 331, 907-924) yielded data indicating a high
      degree of secondary structure. However, the latter also revealed IscU to exist in
      a dynamic equilibrium between two or more distinct conformations, possibly
      existing in a molten globule state. Herein, we further characterize the molten
      globule characteristics of T. maritima IscU by near-ultraviolet circular
      dichroism, 1-anilino-8-naphthalenesulfonic acid binding, free energy of
      unfolding, hydrodynamic radius measurements, and limited tryptic digestion. The
      data suggest unusual dynamic behavior that is not fully consistent with typical
      protein states such as fully folded, fully unfolded, or molten globule. For
      instance, the existence of a stable tertiary fold is supported by near-UV CD
      spectra and hydrodynamic radius measurements, whereas other data are less clearly
      interpretable and may be viewed as consistent with either a molten globule or
      fully folded state. However, all of the data are consistent with our previous
      hypothesis of a protein sampling multiple discrete tertiary conformations in
      which these structural transitions occur on a "slow" time scale. To describe such
      proteins, we introduce the term multiple discrete conformers.

PMID- 14688266
TI  - Motifs IV and V in the DEAH box splicing factor Prp22 are important for RNA
      unwinding, and helicase-defective Prp22 mutants are suppressed by Prp8.
AB  - The yeast pre-mRNA splicing factor Prp22 is a member of the DEAH box family of
      nucleic acid-stimulated ATPases and RNA helicases. Here we report a mutational
      analysis of 16 conserved residues in motifs Ia ((534)TQPRRVAA(541)), IV
      ((695)LVFLTG(700)), and V ((757)TNIAETSIT(765)). Mutants T757A, I764A, and T765A
      were lethal, and F697A cells did not grow at < or =30 degrees C. The mutant
      proteins failed to catalyze mRNA release from the spliceosome in vitro, and they
      were deficient for RNA unwinding. The F697A, I764A, and T765A proteins were
      active for ATP hydrolysis in the presence of RNA cofactor. The T757A mutant
      retained basal ATPase activity but was not stimulated by RNA, whereas ATP
      hydrolysis by T765A was strictly dependent on the RNA cofactor. Thus Thr-757 and
      Thr-765 in motif V link ATP hydrolysis to the RNA cofactor. To illuminate the
      mechanism of Prp22-catalyzed mRNA release, we performed a genetic screen to
      identify extragenic suppressors of the cold-sensitive growth defect of a
      helicase/release-defective Prp22 mutant. We identified one of the suppressors as
      a missense mutation of PRP8 (R1753K), a protein component of the U5 small nuclear
      ribonucleoprotein. We show that PRP8-R1753K suppressed multiple helicase
      deficient prp22 mutations, including the lethal I764A mutation. Replacing Arg
      1753 of Prp8 by either Lys, Ala, Gln, or Glu resulted in suppression of helicase
      defective Prp22 mutants. Prp8-Arg1753 mutations by themselves caused temperature
      sensitive growth defects in a PRP22 strain. These findings suggest a model
      whereby Prp22 disrupts an RNA/protein or RNA/RNA interaction in the spliceosome
      that is normally stabilized by Prp8.

PMID- 14688267
TI  - Small interfering RNA targeting heme oxygenase-1 enhances ischemia-reperfusion
      induced lung apoptosis.
AB  - Heme oxygenase-1 (HO-1) is emerging as an important cytoprotective enzyme system
      in a variety of injury models. To optimize future therapeutic applications of HO
      1, it is necessary to delineate the precise functions and mechanisms as well as
      modes of externally regulating HO-1 expression. Investigations have been limited
      by difficulties with the generation of HO-1 null mice and the lack of specific HO
      1 inhibitors. Lung ischemia-reperfusion (I-R) injury is the inciting event in
      acute lung failure following transplantation, surgery, and shock. To study the
      function of HO-1 in I-R-induced lung injury, we designed small interfering RNA
      (siRNA) sequences that effectively suppress HO-1 expression both in vitro and in
      vivo in an organ-specific manner. In this study we show that there is enhanced
      apoptosis, via increased Fas expression and caspase 3 activity, in the presence
      of HO-1 siRNA in endothelial cells and mouse lung during I-R injury, whereas HO-1
      overexpression attenuates apoptosis. To the best of our knowledge, we are the
      first to demonstrate that lung-specific siRNA delivery can be achieved by
      intranasal administration without the need for viral vectors or transfection
      agents in vivo, thereby obviating potential concerns for toxicity if siRNA
      technology is to have clinical application in the future.

PMID- 14688268
TI  - CAG repeat lengths in X- and Y-bearing sperm indicate that gender bias during
      transmission of Huntington's disease gene is determined in the embryo.
AB  - The size of the CAG tract at the Huntington's disease (HD) locus upon
      transmission depends on the gender of the parent. However, the basis for the
      parent-of-origin effect is unknown. To test whether expansion and contraction in
      HD are "imprinted" in the germ cells, we isolated the X- and Y-bearing sperm of
      HD transgenic mice. Here we show that CAG repeat distributions in the X- and Y
      bearing spermatozoa of founding fathers do not differ. These data show that
      gender-dependent changes in CAG repeat length arise in the embryo.

PMID- 14688269
TI  - Determinants of substrate recognition by the Escherichia coli multidrug
      transporter MdfA identified on both sides of the membrane.
AB  - The Escherichia coli multidrug transporter MdfA contains a membrane-embedded
      charged residue (Glu-26) that was shown to play an important role in substrate
      recognition. To identify additional determinants of multidrug recognition we
      isolated 58 intragenic second-site mutations that restored the function of
      inactive MdfA E26X mutants. In addition, two single-site mutations that enhanced
      the activity of wild-type MdfA were identified. Most of the mutations were found
      in two regions, the cytoplasmic half of transmembrane segments (TMs) 4, 5, and 6
      (cluster 1) and the periplasmic half of TM 1 and 2 (cluster 2). The identified
      residues were mutated to cysteines in the background of a functional cysteine
      less MdfA, and substrate protection against alkylation was analyzed. The results
      support the suggestion that the two clusters are involved in substrate
      recognition. Using inverted membrane vesicles we observed that a proton
      electrochemical gradient (Deltamicro(H(+)), inside positive and acidic) enhanced
      the substrate-protective effect in the cytoplasmic region, whereas it largely
      reduced this effect in the periplasmic side of MdfA. Therefore, we propose that
      substrates interact with two sites in MdfA, one in the cytoplasmic leaflet of the
      membrane and the other in the periplasmic leaflet. Theoretically, these domains
      could constitute a large part of the multidrug pathway through MdfA.

PMID- 14688270
TI  - X-ray structure of translation initiation factor eIF2gamma: implications for tRNA
      and eIF2alpha binding.
AB  - The x-ray structure of the gamma-subunit of the heterotrimeric translation
      initiation factor eIF2 has been determined to 2.4-A resolution. eIF2 is a GTPase
      that delivers the initiator Met-tRNA to the P site on the small ribosomal subunit
      during a rate-limiting initiation step in translation. The structure of eIF2gamma
      closely resembles that of EF1A.GTP, consisting of an N-terminal G domain followed
      by two beta-barrels arranged in a closed configuration with domain II packed
      against the G domain in the vicinity of the Switch regions. The G domain of
      eIF2gamma has an unusual zinc ribbon motif, not previously found in other
      GTPases. Structure-based site-directed mutagenesis was used to identify two
      adjacent features on the surface of eIF2gamma that bind the alpha-subunit and Met
      tRNA(i)(Met), respectively. These structural, biochemical, and genetic results
      provide new insights into eIF2 ternary complex assembly.

PMID- 14688271
TI  - Evidence that tyrphostins AG10 and AG18 are mitochondrial uncouplers that alter
      phosphorylation-dependent cell signaling.
AB  - Receptor agonists that initiate fluid secretion in salivary gland epithelial
      cells also increase protein phosphorylation. To assess contributions of tyrosine
      phosphorylation to secretion, changes in muscarinic receptor-initiated secretion
      (estimated from sodium pump-dependent increases in oxygen consumption) were
      measured in parotid acinar cells exposed to tyrosine kinase inhibitors. However,
      like the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenyl
      hydrazone, tyrphostins AG10 and AG18 increased the rate of oxygen consumption and
      reduced cellular ATP by approximately 90% in the absence of the muscarinic
      agonist carbachol, indicating that these tyrphostins uncouple mitochondria.
      Exposure of isolated mitochondria to five structurally related tyrphostins
      demonstrated that their relative potencies as uncouplers differed from their in
      vitro kinase-inhibitory potencies due to different molecular requirements for the
      two effects. AG10 and AG18 blocked parotid phosphorylation events only at
      concentrations that reduced ATP content. The tyrosine kinase inhibitor genistein
      reduced ATP content by 15-20% and weakly uncoupled isolated mitochondria, but its
      inhibition of carbachol-mediated protein kinase Cdelta tyrosine phosphorylation
      and ERK1/2 activation appeared attributable to blocking tyrosine kinases
      directly. Carbachol itself rapidly reduced ATP content by 15-20%. Carbachol, 3'-O
      (4-benzoyl)benzoyl adenosine 5'-triphosphate (P2X(7) receptor agonist), AG10,
      AG18, and carbonyl cyanide p-trifluoromethoxyphenyl hydrazone rapidly activated
      the fuel sensor AMP-activated protein kinase (AMPK); however, only AMPK
      activation by carbachol and BzATP was due to sodium pump stimulation. AG10 and
      AG18 also activated AMPK and/or uncoupled mitochondria in PC12, HeLa, and HEK293
      cells. These studies demonstrate that some tyrosine kinase inhibitors produce
      cellular effects that are mechanistically different from their primary in vitro
      characterizations and, as do salivary secretory stimuli, promote rapid metabolic
      alterations that initiate secondary signaling events.

PMID- 14688272
TI  - Oxidative stress is a mediator of glucose toxicity in insulin-secreting
      pancreatic islet cell lines.
AB  - Pancreatic beta cells secrete insulin in response to changes in the extracellular
      glucose. However, prolonged exposure to elevated glucose exerts toxic effects on
      beta cells and results in beta cell dysfunction and ultimately beta cell death
      (glucose toxicity). To investigate the mechanism of how increased extracellular
      glucose is toxic to beta cells, we used two model systems where glucose
      metabolism was increased in beta cell lines by enhancing glucokinase (GK)
      activity and exposing cells to physiologically relevant increases in
      extracellular glucose (3.3-20 mm). Exposure of cells with enhanced GK activity to
      20 mm glucose accelerated glycolysis, but reduced cellular NAD(P)H and ATP,
      caused accumulation of intracellular reactive oxygen species (ROS) and oxidative
      damage to mitochondria and DNA, and promoted apoptotic cell death. These changes
      required both enhanced GK activity and exposure to elevated extracellular
      glucose. A ROS scavenger partially prevented the toxic effects of increased
      glucose metabolism. These results indicate that increased glucose metabolism in
      beta cells generates oxidative stress and impairs cell function and survival;
      this may be a mechanism of glucose toxicity in beta cells. The level of beta cell
      GK may also be critical in this process.

PMID- 14688273
TI  - Phosphatidylinositol 3-kinase and mTOR signaling pathways regulate RNA polymerase
      I transcription in response to IGF-1 and nutrients.
AB  - Regulation of ribosomal RNA gene transcription by RNA polymerase I (Pol I) is
      fundamental to ribosome biogenesis and therefore protein translation capacity and
      cell growth, yet little is known of the key signaling cascades involved. We show
      here that insulin-like growth factor-1 (IGF-1)-induced Pol I transcription in
      HEK293 cells is entirely dependent on phosphatidylinositol 3-kinase (PI3K)
      activity and, additionally, is modulated by the mammalian target of rapamycin
      (mTOR), which coordinates Pol I transcription with the availability of amino
      acids. The mitogen-activated protein kinase (MAPK) pathway is weakly stimulated
      by IGF-1 in these cells and partly contributes to Pol I transcription regulation.
      Activation of Pol I transcription by IGF-1 results from enhancement of the
      activity of the Pol I transcription machinery and increased occupancy by SL1 of
      the endogenous tandemly repeated ribosomal promoters in vivo. The inputs from
      PI3K, mTOR, and MAPK pathways converge to direct appropriate rRNA gene expression
      by Pol I in the nucleolus of mammalian cells in response to environmental cues,
      such as growth factors and nutrients.

PMID- 14688274
TI  - Organization of the AAA(+) adaptor protein PspA is an oligomeric ring.
AB  - The 25.3 kDa "adaptor" protein, PspA (phage shock protein A), is found in the
      cytoplasm and in association with the inner membrane of certain bacteria. PspA
      plays critical roles in negatively regulating the phage shock response and
      maintaining membrane integrity, especially during the export of proteins such as
      virulence factors. Homologues of PspA function exist for thylakoid biogenesis.
      Here we report the first three-dimensional reconstruction of a PspA assembly from
      Escherichia coli, visualized by electron microscopy and single particle analysis
      to a resolution of 30 Angstroms. The assembly forms a 9-fold rotationally
      symmetric ring with an outer diameter of 200 Angstroms, an inner diameter of 95
      Angstroms, and a height of approximately 85 Angstroms. The molecular mass of the
      complex was calculated to be 1023 kDa by size exclusion chromatography,
      suggesting that each of the nine domains is likely to be composed of four PspA
      subunits. The functional implications of this PspA structure are discussed in
      terms of its interaction with the protein export machinery of the bacterial cell
      and its AAA(+) protein partner, PspF.

PMID- 14688276
TI  - Translational control of tumor necrosis factor-related apoptosis-inducing ligand
      death receptor expression in melanoma cells.
AB  - In the present study, it was found that tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL)-R2 protein expression did not correlate with mRNA
      expression in melanoma cell lines. In particular, early passage primary cultures
      from patients had low TRAIL-R2 protein expression compared with later passage
      cultures although TRAIL-R2 mRNA expression was similar in early and late
      passages. Similarly, cell lines made resistant to TRAIL by cultures in TRAIL had
      low TRAIL-R2 protein expression but normal levels of mRNA for TRAIL-R2.
      Expression from a luciferase reporter gene construct with the 3'-untranslated
      region (UTR) (but not the 5'-UTR) of TRAIL-R2 was suppressed when transfected
      into the TRAIL-selected (resistant) melanoma lines compared with that seen in the
      parental (sensitive) lines. Similar results were seen in early passage
      (resistant) cultures compared with late passage (sensitive) primary melanoma
      cultures. RNA gel shift assays demonstrated protein(s) binding to the 3'-UTR of
      TRAIL-R2 mRNA that were more evident in TRAIL-resistant cultures with low TRAIL
      R2 protein expression. A 23-base fragment of the 3'-UTR inhibited binding of the
      proteins to the 3'-UTR, and a probe using this fragment bound to proteins in
      TRAIL-selected melanoma lines and early passage isolates of melanoma. Binding of
      the 3'-UTR probe to the cytosolic protein(s) was induced by exposure to TRAIL and
      was lost from the TRAIL selected lines 2-3 days after withdrawal of TRAIL from
      the cultures. These results are consistent with post-transcriptional regulation
      of TRAIL-R2 expression by cytosolic proteins induced by TRAIL that bind to the 3'
      UTR region of TRAIL-R2 mRNA.

PMID- 14688277
TI  - Cohesin-dockerin interactions within and between Clostridium josui and
      Clostridium thermocellum: binding selectivity between cognate dockerin and
      cohesin domains and species specificity.
AB  - The cellulosome components are assembled into the cellulosome complex by the
      interaction between one of the repeated cohesin domains of a scaffolding protein
      and the dockerin domain of an enzyme component. We prepared five recombinant
      cohesin polypeptides of the Clostridium thermocellum scaffolding protein CipA,
      two dockerin polypeptides of C. thermocellum Xyn11A and Xyn10C, four cohesin
      polypeptides of Clostridium josui CipA, and two dockerin polypeptides of C. josui
      Aga27A and Cel8A, and qualitatively and quantitatively examined the cohesin
      dockerin interactions within C. thermocellum and C. josui, respectively, and the
      species specificity of the cohesin-dockerin interactions between these two
      bacteria. Surface plasmon resonance (SPR) analysis indicated that there was a
      certain selectivity, with a maximal 34-fold difference in the K(D) values, in the
      cohesin-dockerin interactions within a combination of C. josui, although this was
      not detected by qualitative analysis. Affinity blotting analysis suggested that
      there was at least one exception to the species specificity in the cohesin
      dockerin interactions, although species specificity was generally conserved among
      the cohesin and dockerin polypeptides from C. thermocellum and C. josui, i.e. the
      dockerin polypeptides of C. thermocellum Xyn11A exceptionally bound to the
      cohesin polypeptides from C. josui CipA. SPR analysis confirmed this exceptional
      binding. We discuss the relationship between the species specificity of the
      cohesin-dockerin binding and the conserved amino acid residues in the dockerin
      domains.

PMID- 14688275
TI  - Menin induces apoptosis in murine embryonic fibroblasts.
AB  - Multiple endocrine neoplasia type I (MEN1) is a hereditary tumor syndrome
      characterized by multiple endocrine and occasionally non-endocrine tumors. The
      tumor suppressor gene Men1, which is frequently mutated in MEN1 patients, encodes
      the nuclear protein menin. Although many tumor suppressor genes are involved in
      the regulation of apoptosis, it is unclear whether menin facilitates apoptosis.
      Here we show that ectopic overexpression of menin via adenoviruses induces
      apoptosis in murine embryonic fibroblasts. The induction of apoptosis depends on
      Bax and Bak, two proapoptotic proteins. Moreover, loss of menin expression
      compromises apoptosis induced by UV irradiation and tumor necrosis factor-alpha
      (TNF-alpha), whereas complementation of menin-null cells with menin restores
      sensitivity to UV- and TNF-alpha-induced apoptosis. Interestingly, loss of menin
      reduces the expression of procaspase 8, a critical protease that is essential for
      apoptosis induced by death-related receptors, whereas complementation of the
      menin-null cells up-regulates the expression of procaspase 8. Furthermore,
      complementation of menin-null cells with menin increases the activation of
      caspase 8 in response to TNF-alpha treatment. These results suggest a
      proapoptotic function for menin that may be important in suppressing the
      development of MEN1.

PMID- 14688278
TI  - Activation of m-calpain is required for chromosome alignment on the metaphase
      plate during mitosis.
AB  - Calpains form a superfamily of Ca(2+)-dependent intracellular cysteine proteases
      with various isoforms. Two isoforms, micro- and m-calpains, are ubiquitously
      expressed and known as conventional calpains. It has been previously shown that
      the mammalian calpains are activated during mitosis by transient increases in
      cytosolic Ca(2+) concentration. However, it is still unknown whether the
      activation of calpains contributes to particular events in mitosis. With the use
      of RNA interference (RNAi), we investigated the roles of calpains in mitosis.
      Cells reduced the levels of m-calpain, but not mu-calpain, arrested at
      prometaphase and failed to align their chromosomes at the spindle equator.
      Specific peptidyl calpain inhibitors also induced aberrant mitosis with
      chromosome misalignment. Although both m-calpain RNAi and calpain inhibitors
      affected neither the separation of centrosomes nor the assembly of bipolar
      spindles, Mad2 was detected on the kinetochores of the misaligned chromosomes,
      indicating that the prometaphase arrest induced by calpain inhibition is due to
      activation of the spindle assembly checkpoint. Furthermore, when calpain activity
      was inhibited in cells having monopolar spindles, chromosomes were clustered
      adjacent to the centrosome, suggesting that calpain activity is involved in a
      polar ejection force for metaphase alignment of chromosomes. Based on these
      findings, we propose that activation of m-calpain during mitosis is required for
      cells to establish the chromosome alignment by regulating some molecules that
      generate polar ejection force.

PMID- 14688279
TI  - Structural determinants regulating expression of the high affinity leukotriene B4
      receptor: involvement of dileucine motifs and alpha-helix VIII.
AB  - Mutational analysis of determinants located in the C-terminal (C) tail of the
      high affinity leukotriene (LT) B(4) receptor, BLT1, was performed to assess their
      significance in BLT1 trafficking. When expressed in COS-7 cells, a BLT1 deletion
      mutant lacking the C-tail (G291stop) displayed higher numbers of binding sites
      and increased signal transduction compared with wild-type (WT) BLT1. Addition of
      the C-tail from either the platelet-activating factor receptor or the LTD(4)
      receptor, CysLT1, did not restore WT phenotype. Moreover, the number of LTB(4)
      binding sites was higher in the chimeras than in the WT BLT1, suggesting the
      requirement for specific structural determinants within the BLT1 C-tail.
      Elimination of a distal C-tail dileucine motif (Leu(304)-Leu(305)), but not the
      proximal (Leu(292)-Leu(293)) motif, altered BLT1 pharmacological characteristics
      and caused a moderate constitutive receptor activation. Surprisingly, all mutant
      receptors were efficiently delivered to the plasma membrane, but not to a greater
      extent than WT BLT1, as assessed by flow cytometry. Furthermore, substitution of
      Leu(304)-Leu(305) prevented LTB(4)-induced BLT1 internalization. Molecular
      modeling of BLT1 on the bovine rhodopsin receptor scaffold strongly suggested the
      involvement of the distal dileucine motif (Leu(304)-Leu(305)) in a hydrophobic
      core, including intrahelical interactions within alpha-helix VIII and
      interhelical interactions with residues of helix I. Disruption of this
      hydrophobic core is proposed to increase the population of receptors in the
      active form, to restrain their trafficking and to facilitate the activation of
      BLT1 as indicated by the increased maximal level of binding of the ligand and
      constitutive activation of the receptor.

PMID- 14688280
TI  - Dynamic changes in C-Raf phosphorylation and 14-3-3 protein binding in response
      to growth factor stimulation: differential roles of 14-3-3 protein binding sites.
AB  - Phosphorylation events play a crucial role in Raf activation. Phosphorylation of
      serines 259 and 621 in C-Raf and serines 364 and 728 in B-Raf has been suggested
      to be critical for association with 14-3-3 proteins. To study the functional
      consequences of Raf phosphorylations at these positions, we developed and
      characterized phosphospecific antibodies directed against 14-3-3 binding
      epitopes: a monoclonal phosphospecific antibody (6B4) directed against pS621 and
      a polyclonal antibody specific for B-Raf-pS364 epitope. Although 6B4 detected
      both C- and B-Raf in Western blots, it specifically recognizes the native form of
      C-Raf but not B-Raf. Contrary to B-Raf, a kinase-dead mutant of C-Raf was found
      to be only poorly phosphorylated in the Ser-621 position. Moreover, serine 259 to
      alanine mutation prevented the Ser-621 phosphorylation suggesting an
      interdependence between these two 14-3-3 binding domains. Direct C-Raf.14-3-3
      binding studies with purified proteins combined with competition assays revealed
      that the 14-3-3 binding domain surrounding pS621 represents the high affinity
      binding site, whereas the pS259 epitope mediates lower affinity binding. Raf
      isozymes differ in their 14-3-3 association rates. The time course of endogenous
      C-Raf activation in mammalian cells by nerve growth factor (NGF) has been
      examined using both phosphospecific antibodies directed against 14-3-3 binding
      sites (6B4 and anti-pS259) as well as phosphospecific antibodies directed against
      the activation domain (anti-pS338 and anti-pY340/pY341). Time course of Ser-621
      phosphorylation, in contrast to Ser-259 phosphorylation, exhibited unexpected
      pattern reaching maximal phosphorylation within 30 s of NGF stimulation.
      Phosphorylation of tyrosine 340/341 reached maximal levels subsequent to Ser-621
      phosphorylation and was coincident with emergence of kinase activity. Taken
      together, we found substantial differences between C-Raf.14-3-3 binding epitopes
      pS259 and pS621 and visualized for the first time the sequence of the essential C
      Raf phosphorylation events in mammalian cells in response to growth factor
      stimulation.

PMID- 14688281
TI  - Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3
      kinase/Akt pathway and the Nrf2 transcription factor in response to the
      antioxidant phytochemical carnosol.
AB  - The phosphatidylinositol 3-kinase (PI3K)/Akt pathway elicits a survival signal
      against multiple apoptotic insults. In addition, phase II enzymes such as heme
      oxygenase-1 (HO-1) protect cells against diverse toxins and oxidative stress. In
      this work, we describe a link between these defense systems at the level of
      transcriptional regulation of the antioxidant enzyme HO-1. The herb-derived
      phenol carnosol induced HO-1 expression at both mRNA and protein levels.
      Luciferase reporter assays indicated that carnosol targeted the mouse ho1
      promoter at two enhancer regions comprising the antioxidant response elements
      (AREs). Moreover, carnosol increased the nuclear levels of Nrf2, a transcription
      factor governing AREs. Electrophoretic mobility shift assays and luciferase
      reporter assays with a dominant-negative Nrf2 mutant indicated that carnosol
      increased the binding of Nrf2 to ARE and induced Nrf2-dependent activation of the
      ho1 promoter. While investigating the signaling pathways responsible for HO-1
      induction, we observed that carnosol activated the ERK, p38, and JNK pathways as
      well as the survival pathway driven by PI3K. Inhibition of PI3K reduced the
      increase in Nrf2 protein levels and activation of the ho1 promoter. Expression of
      active PI3K-CAAX (where A is aliphatic amino acid) was sufficient to activate
      AREs. The use of dominant-negative mutants of protein kinase Czeta and Akt1, two
      kinases downstream from PI3K, demonstrated a requirement for active Akt1, but not
      protein kinase Czeta. Moreover, the long-term antioxidant effect of carnosol was
      partially blocked by PI3K or HO-1 inhibitors, further demonstrating that carnosol
      attenuates oxidative stress through a pathway that involves PI3K and HO-1.

PMID- 14688282
TI  - Distinct roles of Smad2-, Smad3-, and ERK-dependent pathways in transforming
      growth factor-beta1 regulation of pancreatic stellate cellular functions.
AB  - Pancreatic stellate cells (PSCs) play a major role in promoting pancreatic
      fibrosis. Transforming growth factor-beta(1) (TGF-beta(1)) regulates PSC
      activation and proliferation in an autocrine manner. The intracellular signaling
      pathways of the regulation were examined in this study. Immunoprecipitation and
      immunocytochemistry revealed that Smad2, Smad3, and Smad4 were functionally
      expressed in PSCs. Adenovirus-mediated expression of Smad2, Smad3, or dominant
      negative Smad2/3 did not alter TGF-beta(1) mRNA expression level or the amount of
      autocrine TGF-beta(1) peptide. However, expression of dominant-negative Smad2/3
      inhibited PSC activation and enhanced their proliferation. Co-expression of Smad2
      with dominant-negative Smad2/3 restored PSC activation inhibited by dominant
      negative Smad2/3 expression without changing their proliferation. By contrast, co
      expression of Smad3 with dominant-negative Smad2/3 attenuated PSC proliferation
      enhanced by dominant-negative Smad2/3 expression without altering their
      activation. Exogenous TGF-beta(1) increased TGFbeta(1) mRNA expression in PSCs.
      However, PD98059, a specific inhibitor of mitogen-activated protein kinase kinase
      (MEK1), inhibited ERK activation by TGF-beta(1), and consequently attenuated TGF
      beta(1) enhancement of its own mRNA expression in PSCs. We propose that TGF
      beta(1) differentially regulates PSC activation, proliferation, and TGF-beta(1)
      mRNA expression through Smad2-, Smad3-, and ERK-dependent pathways, respectively.

PMID- 14688283
TI  - Glycosylation affects the protein stability and cell surface expression of Kv1.4
      but Not Kv1.1 potassium channels. A pore region determinant dictates the effect
      of glycosylation on trafficking.
AB  - Kv1.1 and Kv1.4 potassium channels are plasma membrane glycoproteins involved in
      action potential repolarization. We have shown previously that glycosylation
      affects the gating function of Kv1.1 and that a pore region determinant of Kv1.1
      and Kv1.4 affects their cell surface trafficking negatively or positively,
      respectively. Here we investigated the role of N-glycosylation of Kv1.1 and Kv1.4
      on their protein stability, cellular localization pattern, and trafficking to the
      cell surface. We found that preventing N-glycosylation of Kv1.4 decreased its
      protein stability, induced its high partial intracellular retention, and
      decreased its cell surface protein levels, whereas it had little or no effect on
      these parameters for Kv1.1. Exchanging a trafficking pore region determinant
      between Kv1.1 and Kv1.4 reversed these effects of glycosylation on these chimeric
      channels. Thus it appeared that the Kv1.4 pore region determinant and the sugar
      tree attached to the S1-S2 linker showed some type of dependence in promoting
      proper trafficking of the protein to the cell surface, and this dependence can be
      transferred to chimeric Kv1.1 proteins that contain the Kv1.4 pore. Understanding
      the different trafficking programs of Kv1 channels, and whether they are altered
      by glycosylation, will highlight the different posttranslational mechanisms
      available to cells to modify their cell surface ion channel levels and possibly
      their signaling characteristics.

PMID- 14688284
TI  - Stimulation of flap endonuclease-1 by the Bloom's syndrome protein.
AB  - Bloom's syndrome (BS) is a rare autosomal recessive genetic disorder associated
      with genomic instability and an elevated risk of cancer. Cellular features of BS
      include an accumulation of abnormal replication intermediates and increased
      sister chromatid exchange. Although it has been suggested that the underlying
      defect responsible for hyper-recombination in BS cells is a temporal delay in the
      maturation of DNA replication intermediates, the precise role of the BS gene
      product, BLM, in DNA metabolism remains elusive. We report here a novel
      interaction of the BLM protein with the human 5'-flap endonuclease/5'-3'
      exonuclease (FEN-1), a genome stability factor involved in Okazaki fragment
      processing and DNA repair. BLM protein stimulates both the endonucleolytic and
      exonucleolytic cleavage activity of FEN-1 and this functional interaction is
      independent of BLM catalytic activity. BLM and FEN-1 are associated with each
      other in human nuclei as shown by their reciprocal co-immunoprecipitation from
      HeLa nuclear extracts. The BLM-FEN-1 physical interaction is mediated through a
      region of the BLM C-terminal domain that shares homology with the FEN-1
      interaction domain of the Werner syndrome protein, a RecQ helicase family member
      homologous to BLM. This study provides the first evidence for a direct
      interaction of BLM with a human nucleolytic enzyme. We suggest that functional
      interactions between RecQ helicases and Rad2 family nucleases serve to process
      DNA substrates that are intermediates in DNA replication and repair.

PMID- 14688285
TI  - Elongation of synthetic RNA templates by hepatitis C virus NS5B polymerase.
AB  - Here we examine the ability of seven, 3'-related, short synthetic RNAs to serve
      as templates for the hepatitis C virus (HCV) polymerase, non-structural protein
      5B (NS5B). These RNAs, termed HL, range from 8 to 16 nucleotides in length, each
      with ACC at the 3' terminus. Interestingly HL12 and longer templates have a
      predicted secondary structure. Those with one or two unpaired adenylates at the
      5'-end of a stem were increased in size by one or two nucleotides, respectively,
      following incubation with NS5B and UTP. Using labeled template RNA and cold UTP,
      extension in size could be inhibited by addition of non-labeled template of the
      same size. This template elongation was not inhibited by cold linear HL10
      template unless pGpG was added. Fluorescence anisotropy demonstrated HL14, a
      template with secondary structure, bound with an apparent K(d) of 22 nm. A linear
      template, HL10, plus pGpG primer was bound by NS5B with a K(d) of 45 nm, whereas
      HL10 alone bound with an apparent K(d) of 182 nm. The amplitude of the template
      extension product was increased by a brief preincubation at 4 degrees C followed
      by incubation at 23 or 30 degrees C. The nucleotide-mediated increase in size
      occurred for both templates that required a mismatch or bulge at the 3'-end as
      well as for those without the mismatch. These results suggest an NS5B active site
      pocket can readily accommodate short templates with four or five base stems and
      initiate copy-back replication in the presence of a one nucleotide mismatch.

PMID- 14688286
TI  - Hepatic de novo synthesis of glucose 6-phosphate is not affected in peroxisome
      proliferator-activated receptor alpha-deficient mice but is preferentially
      directed toward hepatic glycogen stores after a short term fast.
AB  - Apart from impaired beta-oxidation, Pparalpha-deficient (Pparalpha(-/-)) mice
      suffer from hypoglycemia during prolonged fasting, suggesting alterations in
      hepatic glucose metabolism. We compared hepatic glucose metabolism in vivo in
      wild type (WT) and Pparalpha(-/-) mice after a short term fast, applying novel
      isotopic methods. After a 9-h fast, mice were infused with [U-(13)C]glucose, [2
      (13)C]glycerol, [1-(2)H]galactose, and paracetamol for 6 h, and blood and urine
      was collected in timed intervals. Plasma glucose concentrations remained constant
      and were not different between the groups. Hepatic glycogen content was 69 +/- 11
      and 90 +/- 31 microM/g liver after 15 h of fasting in WT and Pparalpha(-/-) mice,
      respectively. The gluconeogenic flux toward glucose 6-phosphate was not different
      between the groups (i.e. 157 +/- 9 and 153 +/- 9 microM/kg/min in WT and
      Pparalpha(-/-) mice, respectively). The gluconeogenic flux toward plasma glucose,
      however, was decreased in PPARalpha(-/-) mice (i.e. 142 +/- 9 versus 124 +/- 13
      microM/kg/min) (p < 0.05), accounting for the observed decrease (-15%) in hepatic
      glucose production in Pparalpha(-/-) mice. Expression of the gene encoding
      glucose-6-phosphate hydrolase (G6ph) was lower in the PPARalpha(-/-) mice
      compared with WT mice. In conclusion, Pparalpha(-/-) mice were able to maintain a
      normal total gluconeogenic flux to glucose 6-phosphate during moderate fasting,
      despite their inability to up-regulate beta-oxidation. However, this
      gluconeogenic flux was directed more toward glycogen, leading to a decreased
      hepatic glucose output. This was associated with a down-regulation of the
      expression of G6ph in PPARalpha-deficient mice.

PMID- 14688287
TI  - Monoglucosyldiacylglycerol, a foreign lipid, can substitute for
      phosphatidylethanolamine in essential membrane-associated functions in
      Escherichia coli.
AB  - The mechanisms by which lipid bilayer properties govern or influence membrane
      protein functions are little understood, but a liquid-crystalline state and the
      presence of anionic and nonbilayer (NB)-prone lipids seem important. An
      Escherichia coli mutant lacking the major membrane lipid phosphatidylethanolamine
      (NB-prone) requires divalent cations for viability and cell integrity and is
      impaired in several membrane functions that are corrected by introduction of the
      "foreign" NB-prone neutral glycolipid alpha-monoglucosyldiacylglycerol (MGlcDAG)
      synthesized by the MGlcDAG synthase from Acholeplasma laidlawii. Dependence on
      Mg(2+) was reduced, and cellular yields and division malfunction were greatly
      improved. The increased passive membrane permeability of the mutant was not
      abolished, but protein-mediated osmotic stress adaptation to salts and sucrose
      was recovered by the presence of MGlcDAG. MGlcDAG also restored tryptophan
      prototrophy and active transport function of lactose permease, both critically
      dependent on phosphatidylethanolamine. Three mechanisms can explain the observed
      effects: NB-prone MGlcDAG improves the quenched lateral pressure profile across
      the bilayer; neutral MGlcDAG dilutes the high anionic lipid surface charge;
      MGlcDAG provides a neutral lipid that can hydrogen bond and/or partially ionize.
      The reduced dependence on Mg(2+) and lack of correction by high monovalent salts
      strongly support the essential nature of the NB properties of MGlcDAG.

PMID- 14688288
TI  - cAMP Dose-dependently prevents palmitate-induced apoptosis by both protein kinase
      A- and cAMP-guanine nucleotide exchange factor-dependent pathways in beta-cells.
AB  - Lipid accumulation in pancreatic beta-cells is thought to cause its dysfunction
      and/or destruction via apoptosis. Our studies show that incubation of the beta
      cell line RINm5F with the saturated free fatty acids (FFA) palmitate caused
      apoptosis based on increases in caspase 3 activity, Annexin V staining, and cell
      death. Furthermore, exposure of RINm5F cells to cAMP-increasing agents, 3
      isobutyl-1-methylxanthine (IBMX), and forskolin completely abolished palmitate
      mediated caspase 3 activity and significantly inhibited Annexin V staining and
      cell death. The cyclic AMP analogs cpt-cAMP and dibutyryl-cAMP mimicked the
      protective effects of IBMX and forskolin, suggesting that cAMP is the mediator of
      the anti-apoptotic effects. The protective action of IBMX and forskolin was rapid
      and did not appear to require gene transcription or new protein synthesis.
      However, these protective effects were clearly independent of protein kinase A
      (PKA) because of the lack of inhibition by the PKA inhibitors H-89 and KT5720. In
      attempts to identify this PKA-independent mechanism, we found that the newly
      developed cAMP analog 8CPT-2Me-cAMP, which selectively activates the cAMP
      dependent guanine nucleotide exchange factor (cAMP-GEF) pathway, mimicked the
      protective effects of IBMX and forskolin, suggesting that the cAMP-GEF pathway is
      involved. In addition, both glucagon-like peptide (GLP-1) and its receptor
      agonist, Exenatide, inhibited palmitate-mediated caspase 3 activation in a dose
      dependent manner. Unexpectedly, H-89 partially reversed the protective effects of
      GLP-1 and Exenatide, suggesting that PKA may play a role in the protective
      effects of these incretins. To explain these seemingly conflicting results, we
      demonstrated that low concentrations of cAMP produced by GLP-1 and Exenatide
      preferentially activate the PKA pathway, whereas higher cAMP concentrations
      produced by IBMX and forskolin activate the more dominant cAMP-GEF pathway. Taken
      together, these results indicate that intracellular concentrations of cAMP may
      play a key role in determining divergent signaling pathways that lead to
      antiapoptotic responses.

PMID- 14688290
TI  - Substrate-dependent and organ-specific chloroplast protein import in planta.
AB  - The NADPH-dependent protochlorophyllide (Pchlide) oxidoreductase (POR) is unique
      because it is a photoenzyme that requires light for its catalytic activity and
      uses Pchlide itself as a photoreceptor. In Arabidopsis, there are three
      structurally related PORs, denoted PORA, PORB, and PORC. The import of one of
      them, PORA, into plastids of cotyledons is substrate dependent. This substrate
      dependence is demonstrated in intact seedlings of wild-type Arabidopsis and two
      mutants, xantha2, which is devoid of Pchlide, and flu, which upon redarkening
      rapidly accumulates Pchlide. In true leaves, PORA uptake does not require the
      presence of Pchlide. The organ specificity of the substrate-dependent import of
      PORA reveals a means of controlling plastid protein translocation that is closely
      associated with a key step in plant development, the light-dependent
      transformation of cotyledons from a storage organ to a photosynthetically active
      leaf.

PMID- 14688289
TI  - Maize mutants lacking chloroplast FtsY exhibit pleiotropic defects in the
      biogenesis of thylakoid membranes.
AB  - A chloroplast signal recognition particle (SRP) that is related to the SRP
      involved in secretion in bacteria and eukaryotic cells is used for the insertion
      of light-harvesting chlorophyll proteins (LHCPs) into the thylakoid membranes. A
      conserved component of the SRP mechanism is a membrane-bound SRP receptor,
      denoted FtsY in bacteria. Plant genomes encode FtsY homologs that are targeted to
      the chloroplast (cpFtsY). To investigate the in vivo roles of cpFtsY, we
      characterized maize cpFtsY and maize mutants having a Mu transposon insertion in
      the corresponding gene (chloroplast SRP receptor1, or csr1). Maize cpFtsY
      accumulates to much higher levels in leaf tissue than in roots and stems.
      Interestingly, it is present at similar levels in etiolated and green leaf tissue
      and was found to bind the prolamellar bodies of etioplasts. A null cpFtsY mutant,
      csr1-1, showed a substantial loss of leaf chlorophyll, whereas a "leaky" allele,
      csr1-3, conditioned a more moderate chlorophyll deficiency. Both alleles caused
      the loss of various LHCPs and the thylakoid-bound photosynthetic enzyme complexes
      and were seedling lethal. By contrast, levels of the membrane-bound components of
      the thylakoid protein transport machineries were not altered. The thylakoid
      membranes in csr1-1 chloroplasts were unstacked and reduced in abundance, but the
      prolamellar bodies in mutant etioplasts appeared normal. These results
      demonstrate the essentiality of cpFtsY for the biogenesis not only of the LHCPs
      but also for the assembly of the other membrane-bound components of the
      photosynthetic apparatus.

PMID- 14688291
TI  - Programmed cell death remodels lace plant leaf shape during development.
AB  - Programmed cell death (PCD) functions in the developmental remodeling of leaf
      shape in higher plants, a process analogous to digit formation in the vertebrate
      limb. In this study, we provide a cytological characterization of the time course
      of events as PCD remodels young expanding leaves of the lace plant. Tonoplast
      rupture is the first PCD event in this system, indicated by alterations in
      cytoplasmic streaming, loss of anthocyanin color, and ultrastructural appearance.
      Nuclei become terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling positive soon afterward but do not become morphologically altered until
      late stages of PCD. Genomic DNA is fragmented, but not into internucleosomal
      units. Other cytoplasmic changes, such as shrinkage and degradation of
      organelles, occur later. This form of PCD resembles tracheary element
      differentiation in cytological execution but requires unique developmental
      regulation so that discrete panels of tissue located equidistantly between veins
      undergo PCD while surrounding cells do not.

PMID- 14688292
TI  - Plant eR genes that encode photorespiratory enzymes confer resistance against
      disease.
AB  - Downy mildew caused by the oomycete pathogen Pseudoperonospora cubensis is a
      devastating foliar disease of cucurbits worldwide. We previously demonstrated
      that the wild melon line PI 124111F (PI) is highly resistant to all pathotypes of
      P. cubensis. That resistance was controlled genetically by two partially
      dominant, complementary loci. Here, we show that unlike other plant disease
      resistance genes, which confer an ability to resist infection by pathogens
      expressing corresponding avirulence genes, the resistance of PI to P. cubensis is
      controlled by enhanced expression of the enzymatic resistance (eR) genes At1 and
      At2. These constitutively expressed genes encode the photorespiratory peroxisomal
      enzyme proteins glyoxylate aminotransferases. The low expression of At1 and At2
      in susceptible melon lines is regulated mainly at the transcriptional level. This
      regulation is independent of infection with the pathogen. Transgenic melon plants
      overexpressing either of these eR genes displayed enhanced activity of glyoxylate
      aminotransferases and remarkable resistance against P. cubensis. The cloned eR
      genes provide a new resource for developing downy mildew-resistant melon
      varieties.

PMID- 14688293
TI  - Storage protein accumulation in the absence of the vacuolar processing enzyme
      family of cysteine proteases.
AB  - The role(s) of specific proteases in seed protein processing is only vaguely
      understood; indeed, the overall role of processing in stable protein deposition
      has been the subject of more speculation than direct investigation. Seed-type
      members of the vacuolar processing enzyme (VPE) family were hypothesized to
      perform a unique function in seed protein processing, but we demonstrated
      previously that Asn-specific protein processing in developing Arabidopsis seeds
      occurs independently of this VPE activity. Here, we describe the unexpected
      expression of vegetative-type VPEs in developing seeds and test the role(s) of
      all VPEs in seed storage protein accumulation by systematically stacking knockout
      mutant alleles of all four members (alphaVPE, betaVPE, gammaVPE, and deltaVPE) of
      the VPE gene family in Arabidopsis. The complete removal of VPE function in the
      alphavpe betavpe gammavpe deltavpe quadruple mutant resulted in a total shift of
      storage protein accumulation from wild-type processed polypeptides to a finite
      number of prominent alternatively processed polypeptides cleaved at sites other
      than the conserved Asn residues targeted by VPE. Although alternatively
      proteolyzed legumin-type globulin polypeptides largely accumulated as
      intrasubunit disulfide-linked polypeptides with apparent molecular masses similar
      to those of VPE-processed legumin polypeptides, they showed markedly altered
      solubility and protein assembly characteristics. Instead of forming 11S hexamers,
      alternatively processed legumin polypeptides were deposited primarily as 9S
      complexes. However, despite the impact on seed protein processing, plants devoid
      of all known functional VPE genes appeared unchanged with regard to protein
      content in mature seeds, relative mobilization rates of protein reserves during
      germination, and vegetative growth. These findings indicate that VPE-mediated Asn
      specific proteolytic processing, and the physiochemical property changes
      attributed to this specific processing step, are not required for the successful
      deposition and mobilization of seed storage protein in the protein storage
      vacuoles of Arabidopsis seeds.

PMID- 14688294
TI  - KIC, a novel Ca2+ binding protein with one EF-hand motif, interacts with a
      microtubule motor protein and regulates trichome morphogenesis.
AB  - Kinesin-like calmodulin binding protein (KCBP) is a microtubule motor protein
      involved in the regulation of cell division and trichome morphogenesis. Genetic
      studies have shown that KCBP is likely to interact with several other proteins.
      To identify KCBP-interacting proteins, we used the C-terminal region of KCBP in a
      yeast two-hybrid screen. This screening resulted in the isolation of a novel KCBP
      interacting Ca2+ binding protein (KIC). KIC, with its single EF-hand motif, bound
      Ca2+ at a physiological concentration. Coprecipitation with bacterially expressed
      protein and native KCBP, gel-mobility shift studies, and ATPase assays with the
      KCBP motor confirmed that KIC interacts with KCBP in a Ca2+-dependent manner.
      Interestingly, although both Ca2+-KIC and Ca2+-calmodulin were able to interact
      with KCBP and inhibit its microtubule binding activity, the concentration of Ca2+
      required to inhibit the microtubule-stimulated ATPase activity of KCBP by KIC was
      threefold less than that required for calmodulin. Two KIC-related Ca2+ binding
      proteins and a centrin from Arabidopsis, which contain one and four EF-hand
      motifs, respectively, bound Ca2+ but did not affect microtubule binding and
      microtubule-stimulated ATPase activities of KCBP, indicating the specificity of
      Ca2+ sensors in regulating their targets. Overexpression of KIC in Arabidopsis
      resulted in trichomes with reduced branch number resembling the zwichel/kcbp
      phenotype. These results suggest that KIC modulates the activity of KCBP in
      response to changes in cytosolic Ca2+ and regulates trichome morphogenesis.

PMID- 14688295
TI  - Loss-of-function mutations of the rice GAMYB gene impair alpha-amylase expression
      in aleurone and flower development.
AB  - GAMYB was first isolated as a positive transcriptional regulator of gibberellin
      (GA)-dependent alpha-amylase expression in barley aleurone cells, and its
      molecular and biochemical properties have been well characterized. However, the
      role of GAMYB elsewhere in the plant is not well understood. To investigate the
      molecular function of GAMYB outside of the aleurone cells, we isolated loss-of
      function mutants from a panel of rice mutants produced by the insertion of a
      retrotransposon, Tos17. Through PCR screening using primers for rice GAMYB
      (OsGAMYB) and Tos17, we isolated three independent mutant alleles that contained
      Tos17 inserted in the exon region. No alpha-amylase expression in the endosperm
      was induced in these mutants in response to GA treatment, indicating that the
      Tos17 insertion had knocked out OsGAMYB function. We found no significant defects
      in the growth and development of the mutants at the vegetative stage. After the
      phase transition to the reproductive stage, however, shortened internodes and
      defects in floral organ development, especially a defect in pollen development,
      were observed. On the other hand, no difference was detected in flowering time.
      High-level OsGAMYB expression was detected in the aleurone cells, inflorescence
      shoot apical region, stamen primordia, and tapetum cells of the anther, but only
      low-level expression occurred in organs at the vegetative stage or in the
      elongating stem. These results demonstrate that, in addition to its role in the
      induction of alpha-amylase in aleurone, OsGAMYB also is important for floral
      organ development and essential for pollen development.

PMID- 14688296
TI  - The ASK1 and ASK2 genes are essential for Arabidopsis early development.
AB  - The requirement of CUL1 for Arabidopsis embryogenesis suggests that Skp1-CUL1-F
      box protein (SCF) complexes play important roles during embryo development. Among
      the 21 Arabidopsis Skp1-like genes (ASKs), it is unknown which ASK gene(s) is
      essential for embryo development. In this study, we demonstrate a vital role for
      ASK1 and ASK2 in Arabidopsis embryogenesis and postembryonic development through
      analysis of the ask1 ask2 double mutant. Our detailed analysis indicates that the
      double mutations in both ASK1 and ASK2 affect cell division and cell
      expansion/elongation and cause a developmental delay during embryogenesis and
      lethality in seedling growth. The expression patterns of ASK1 and ASK2 were
      examined further and found to be consistent with their roles in embryogenesis and
      seedling development. We propose that mutations in ASK1 and ASK2 abolish all of
      the ASK1- and ASK2-based SCF and non-SCF complexes, resulting in alteration of
      gene expression and leading to defects in growth and development.

PMID- 14688300
TI  - Dendritic cell differentiation.

PMID- 14688301
TI  - Signaling and cell surface expression of mu H chains in the absence of light
      chains.

PMID- 14688297
TI  - The tomato homolog of CORONATINE-INSENSITIVE1 is required for the maternal
      control of seed maturation, jasmonate-signaled defense responses, and glandular
      trichome development.
AB  - Jasmonic acid (JA) is a fatty acid-derived signaling molecule that regulates a
      broad range of plant defense responses against herbivores and some microbial
      pathogens. Molecular genetic studies in Arabidopsis have established that JA also
      performs a critical role in anther and pollen development but is not essential
      for other developmental aspects of the plant's life cycle. Here, we describe the
      phenotypic and molecular characterization of a sterile mutant of tomato (jasmonic
      acid-insensitive1 [jai1]) that is defective in JA signaling. Although the mutant
      exhibited reduced pollen viability, sterility was caused by a defect in the
      maternal control of seed maturation, which was associated with the loss of
      accumulation of JA-regulated proteinase inhibitor proteins in reproductive
      tissues. jai1 plants exhibited several defense-related phenotypes, including the
      inability to express JA-responsive genes, severely compromised resistance to two
      spotted spider mites, and abnormal development of glandular trichomes. We
      demonstrate that these defects are caused by the loss of function of the tomato
      homolog of CORONATINE-INSENSITIVE1 (COI1), an F-box protein that is required for
      JA-signaled processes in Arabidopsis. These findings indicate that the JA/COI1
      signaling pathway regulates distinct developmental processes in different plants
      and suggest a role for JA in the promotion of glandular trichome-based defenses.

PMID- 14688302
TI  - Regulation of leukocyte transmigration: cell surface interactions and signaling
      events.

PMID- 14688303
TI  - Cutting edge: IL-7-dependent homeostatic proliferation of CD8+ T cells in
      neonatal mice allows the generation of long-lived natural memory T cells.
AB  - Healthy, nonimmunized C57BL/6 (B6) mice contain memory phenotype CD8+ T cells,
      which are assumed to be generated in response to environmental Ags. Since
      neonatal mice are functionally lymphopenic within the first days after birth, we
      investigated the alternative possibility that the memory CD8+ T cells of
      untreated B6 mice are the result of lymphopenia-induced proliferation during
      neonatal life. We show here that adoptively transferred CD8+ T cells proliferate
      in neonatal B6 mice, rapidly produce IFN-gamma, and develop into memory cells
      which are maintained until adulthood. In contrast to CD4+ T cells, neonatal
      lymphopenia-induced proliferation of CD8+ T cells was IL-7 dependent. Thus,
      neonatal lymphopenia seems to allow CD8+ thymic emigrants to undergo lymphopenia
      induced proliferation during early neonatal life to equip the immune system with
      a set of preactivated CD8+ T cells before any infection, which might contribute
      to the rapid initiation of immune responses in the adult.

PMID- 14688304
TI  - Cutting edge: an endogenous pathway to systemic inflammatory response syndrome
      (SIRS)-like reactions through Toll-like receptor 4.
AB  - Systemic inflammatory response syndrome (SIRS) is typically associated with
      trauma, surgery, or acute pancreatitis. SIRS resembles sepsis, triggered by
      exogenous macromolecules such as LPS acting on Toll-like receptors. What triggers
      SIRS in the absence of infection, however, is unknown. In this study, we report
      that a SIRS-like response can be induced in mice by administration of soluble
      heparan sulfate, a glycosaminoglycan associated with nucleated cells and
      extracellular matrices, and by elastase, which cleaves and releases heparan
      sulfate proteoglycans. The ability of heparan sulfate and elastase to induce SIRS
      depends on functional Toll-like receptor 4, because mutant mice lacking that
      receptor or its function do not respond. These results provide a molecular
      explanation for the initiation of SIRS.

PMID- 14688305
TI  - Expression of preproinsulin-2 gene shapes the immune response to preproinsulin in
      normal mice.
AB  - Deciphering mechanisms involved in failure of self tolerance to preproinsulin-2
      is a key issue in type 1 diabetes. We used nonautoimmune 129SV/Pas mice lacking
      preproinsulin-2 to study the immune response to preproinsulin-2. In these mice, a
      T cell response was detected after immunization with several preproinsulin-2
      peptides and confirmed by generating hybridomas. Activation of some of these
      hybridomas by wild-type (wt) islet cells or recombinant murine proinsulin-2
      demonstrated that two epitopes can be generated from the naturally expressed
      protein. Although T cells from wt mice responded to preproinsulin-2 peptides, we
      could not detect a response to the naturally processed epitopes in these mice.
      Moreover, after immunization with recombinant whole proinsulin-2, a T cell
      response was detected in preproinsulin-2-deficient but not in wt mice. This
      suggests that islet preproinsulin-2-autoreactive T cells are functionally
      eliminated in wt mice. We used a transplantation model to evaluate the relevance
      of reactivity to preproinsulin-2 in vivo. Wild-type preproinsulin-2-expressing
      islets transplanted in preproinsulin-2-deficient mice elicited a mononuclear cell
      infiltration and insulin Abs. Graft infiltration was further increased by
      immunization with preproinsulin-2 peptides. Preproinsulin-2 expression thus
      shapes the immune response and prevents self reactivity to the islet. Moreover,
      islet preproinsulin-2 primes an immune response to preproinsulin-2 in deficient
      mice.

PMID- 14688306
TI  - B7 expression on T cells down-regulates immune responses through CTLA-4 ligation
      via T-T interactions [corrections].
AB  - Although B7 on APCs has a well-recognized role in T cell costimulation, little is
      known about the functional significance of constitutive and activation-induced B7
      expression that also occurs on T cells. To analyze the role of B7 on T cells, B7
      1/B7-2-deficient mice (B7 double knockout) and mice overexpressing B7-2
      exclusively on T cells (B7-2 transgenic) were used as T cell donors for
      allogeneic transplant recipients, and graft-vs-host disease (GVHD) was assessed.
      B7 double-knockout T cells resulted in significant GVHD acceleration compared
      with wild-type T cells. Conversely, B7-2 transgenic donor T cells mediated
      reduced GVHD mortality compared with wild-type T cells. Data indicated that B7
      expression on T cells down-regulated alloresponses through CTLA-4 ligation. This
      study is the first to provide definitive in vivo data illustrating the importance
      of T cell-associated B7 as a negative regulator of immune responses in a
      clinically relevant murine model of GVHD. The up-regulation of B7 on T cells may
      be an important component of normal immune homeostasis.

PMID- 14688307
TI  - A role for TCR affinity in regulating naive T cell homeostasis.
AB  - Homeostatic signals that control the overall size and composition of the naive T
      cell pool have recently been identified to arise from contact with self
      MHC/peptide ligands and a cytokine, IL-7. IL-7 presumably serves as a survival
      factor to keep a finite number of naive cells alive by preventing the onset of
      apoptosis, but how TCR signaling from contact with self-MHC/peptide ligands
      regulates homeostasis is unknown. To address this issue, murine polyclonal and
      TCR-transgenic CD8+ cells expressing TCR with different affinities for self
      MHC/peptide ligands, as depicted by the CD5 expression level, were analyzed for
      their ability to respond to and compete for homeostatic factors under normal and
      lymphopenic conditions. The results suggest that the strength of the TCR affinity
      determines the relative "fitness" of naive T cells to compete for factors that
      support cell survival and homeostatic proliferation.

PMID- 14688308
TI  - Essential role for neutrophil recruitment to the liver in concanavalin A-induced
      hepatitis.
AB  - Leukocyte infiltration into the liver is paramount to the development of liver
      injury in hepatitis. Hepatitis occurring after the administration of Con A in
      mice is felt to be a T lymphocyte-mediated disease. In this study, we report that
      neutrophils are the key initiators of lymphocyte recruitment and liver injury
      caused by Con A. The objectives of this study were to investigate the involvement
      of neutrophils in Con A-induced hepatitis in vivo via intravital microscopy.
      After Con A administration, we observed a significant increase in leukocyte
      rolling flux, a decrease in rolling velocity, and an increase in leukocyte
      adhesion to the hepatic microvasculature. Fluorescence microscopy identified that
      within 4 h of Con A administration only a minority of the recruited leukocytes
      were T lymphocytes. Furthermore, immunohistochemistry showed a significant
      increase in neutrophils recruited to the liver post-Con A treatment in
      association with liver cell damage, as reflected by elevated serum alanine
      aminotransferase levels. Using flow cytometry, we observed that Con A could bind
      directly to neutrophils, which resulted in a shedding of L-selectin, an increase
      in beta(2)-integrin expression, and the production of reactive oxidants.
      Following neutrophil depletion, a significant inhibition of Con A-induced CD4+ T
      lymphocyte recruitment to the liver resulted and complete reduction in hepatic
      injury, as assessed by serum alanine aminotransferase levels. In summary, the
      present data support the concept that neutrophils play an important and
      previously unrecognized role in governing Con A-induced CD4+ T cell recruitment
      to the liver and the subsequent development of hepatitis.

PMID- 14688309
TI  - Sensing environmental lipids by dendritic cell modulates its function.
AB  - Because of its oxidative modification during the acute-phase response to an
      aggression, low density lipoprotein (LDL) can be regarded as a source of lipid
      mediators that can act both to promote and inhibit inflammation. This can be
      exemplified by the production of anti-inflammatory oxidized fatty acids and
      proinflammatory lysophosphatidylcholine (LPC) during LDL oxidation. We have shown
      previously that oxidized LDL (oxLDL) plays an active role at the interface
      between innate and adaptive immunity by delivering instructive molecules such as
      LPC, which promotes mature dendritic cell (DC) generation from differentiating
      monocytes. It is shown in this study that LPC affects the signaling pathway of
      peroxisome proliferator-activated receptors (PPARs). LPC-induced DC maturation is
      associated with complete inhibition of PPARgamma activity and up-regulation of
      the activity of an uncharacterized nuclear receptor that bind peroxisome
      proliferator response element. Oxidized fatty acids generated during LDL
      oxidation are natural ligands for PPARgamma and inhibit oxLDL- and LPC-induced
      maturation. Inhibition experiments with synthetic PPARgamma ligands suggested a
      PPARgamma-dependent and independent effect of LPC on DC maturation. Therefore,
      the relative amount of oxidized fatty acids and LPC influences the immunological
      functions of oxLDL on DC, in part by regulating the PPAR pathway. By sensing the
      biochemical composition of lipoprotein particles, the innate immune system may
      thus identify various endogenous signals that influence the immune response
      during the acute-phase reaction. The therapeutic emulsion intralipid also blocks
      LPC action on PPAR activity and DC maturation. Intralipid may thus be an
      alternative therapeutic strategy for some chronic inflammatory diseases.

PMID- 14688310
TI  - Sustained IL-12 signaling is required for Th1 development.
AB  - STAT4 is an essential transcription factor for Th1 cell development. IL-12 and
      IFN-alpha both activate STAT4, but with different kinetics. In this study we
      compared their capacities to drive differentiation of human naive Th cells toward
      the Th1 phenotype. The Th1-polarizing activity of IFN-alpha was much weaker than
      that of IL-12, correlating with a marked difference in the kinetics of STAT4
      activation; the response to IL-12 was sustained (>48 h), whereas the response to
      IFN-alpha was transient (4 h). The continuous presence of IL-12 was required for
      sustained STAT4 activation. Similarly, optimal Th1 polarization was only achieved
      upon prolonged exposure to IL-12 and could not be induced by a transient IL-12
      pulse. Furthermore, the cytokine IL-2 potentiated sustained IL-12/STAT4 responses
      through up-regulation of IL-12R expression and synergized with IL-12 in driving
      Th1 cell development. Transient IFN-alpha responses, on the other hand, were not
      prolonged by IL-2. IFN-alpha treatment induced down-regulation of IFN-alphabeta
      receptor subunit 1, rendering cells refractory to IFN-alpha, but did not trans
      inhibit the IL-12/STAT4 response. These data indicate that sustained IL-12
      signaling is essential for optimal Th1 cell development and that transient
      activation of STAT4 in response to IFN-alpha may explain the poor Th1-polarizing
      capacity of this cytokine. Collectively these data show that the duration of
      cytokine signaling is important for determining the biological response.

PMID- 14688311
TI  - A CD91-positive subset of CD11c+ blood dendritic cells: characterization of the
      APC that functions to enhance adaptive immune responses against CD91-targeted
      antigens.
AB  - Dendritic cells (DC) and other APCs rely on a number of specialized receptors to
      facilitate the uptake and intracellular accumulation of Ags. In this capacity,
      APCs use receptor-mediated endocytosis to enhance Ag presentation and the
      stimulation of Ag-specific T cells. Studies have demonstrated that the targeted
      delivery of Ags in vivo to CD91/the low-density lipoprotein receptor-related
      protein (CD91/LRP) induces enhanced activation of the adaptive immune system.
      However, the APC that mediates these augmented, Ag-specific responses remains to
      be characterized. In this study, we show that a subset of CD11c(+) lineage
      negative (lin(-)) DC expresses the scavenger receptor CD91/LRP and that these
      rare APC are primarily responsible for the T cell activation that occurs
      following CD91/LRP-mediated Ag uptake in whole blood. The targeting of Ags to
      CD91/LRP results in enhanced receptor-mediated uptake within both lin(-) DCs and
      monocytes, and this uptake results in markedly increased T cell activation.
      Finally, purified cellular populations were used to demonstrate that CD11c(+)
      lin(-) DC, but not monocytes, are capable of stimulating T cell activation
      following CD91/LRP-mediated Ag uptake. Therefore, CD11c(+) lin(-) DC use CD91/LRP
      to facilitate the uptake and subsequent presentation of an array of Ags complexed
      within the CD91/LRP ligand, the activated form of alpha2-macroglobulin
      (alpha2M*).

PMID- 14688312
TI  - Rosmarinic acid induces p56lck-dependent apoptosis in Jurkat and peripheral T
      cells via mitochondrial pathway independent from Fas/Fas ligand interaction.
AB  - Apoptosis is one way of controlling immune responses, and a variety of
      immunosuppressive drugs suppress harmful immune responses by inducing apoptosis
      of lymphocytes. In this study we observed that rosmarinic acid, a secondary
      metabolite of herbal plants, induced apoptosis in an p56(lck) (Lck)-dependent
      manner; Lck(+) Jurkat T cells undergo apoptosis in response to rosmarinic acid
      (RosA) treatment, whereas Lck(-) Jurkat subclone J.CaM1.6 cells do not. J.CaM1.6
      cells with various Lck mutants indicated that Lck SH2 domain, but not Lck kinase
      activity, was required for RosA-induced apoptosis. RosA induced apoptosis in the
      absence of a TCR stimulus, and this was not prevented by interruption of the
      Fas/Fas ligand interaction. Instead, RosA-mediated apoptosis involved a
      mitochondrial pathway as indicated by cytochrome c release and the complete
      blockage of apoptosis by an inhibitor of mitochondrial membrane depolarization.
      Both caspase-3 and -8 were indispensable in RosA-induced apoptosis and work
      downstream of mitochondria and caspase-9 in the order of caspase-9/caspase
      3/caspase-8. In freshly isolated human PBMC, RosA specifically induced apoptosis
      of Lck(+) subsets such as T and NK cells, but not Lck-deficient cells, including
      B cells and monocytes. Moreover, RosA's ability to kill T and NK cells was
      restricted to actively proliferating cells, but not to resting cells. In
      conclusion, Lck-dependent apoptotic activity may make RosA an attractive
      therapeutic tool for the treatment of diseases in which T cell apoptosis is
      beneficial.

PMID- 14688313
TI  - The IL-12 signature: NK cell terminal CD56+high stage and effector functions.
AB  - We report that human peripheral NK cells expressing high CD56 levels
      (CD56(+high)) are terminally differentiated cells indistinguishable from mature
      NK cells recently activated in the presence of IL-12, and not a functionally
      distinct NK-cell subset or progenitors to mature CD56(+low) NK cells. CD56(+high)
      NK cells coexpress all differentiation Ags constitutive or inducible in mature
      (CD56(+)) NK cells, except CD16, present at lower level than on most mature NK
      cells. Also, activation markers, activating receptors and adhesion molecules, and
      most inducible receptors are expressed exclusively and constitutively and are
      inducible at higher levels on CD56(+high) than on CD56(+low) NK cells. Consistent
      with their activated phenotype, many CD56(+high) NK cells are cycling and mediate
      heightened effector functions (proliferation, IFN-gamma and IL-10 but not IL-13
      production) in response to IL-12 and other NK cell-specific stimuli. Conversely,
      IL-12 induces on CD56(+low) NK cells all markers constitutively expressed on the
      CD56(+high) NK cells, concomitantly preventing the IL-2 (and IL-15)-inducible
      expression of NKp44 and CD16 re-expression after immune complex-induced down
      modulation, and CD56(-/+low) NK cells acquire a CD56(+high) NK cell phenotype in
      short term in vitro culture with IL-12. The significance of these findings to the
      NK cell-mediated regulation of immune responses and NK cell development is
      discussed.

PMID- 14688314
TI  - The susceptibility to experimental myasthenia gravis of STAT6-/- and STAT4-/-
      BALB/c mice suggests a pathogenic role of Th1 cells.
AB  - Autoantibodies to the muscle acetylcholine receptor (AChR) cause the symptoms of
      human and experimental myasthenia gravis (EMG). AChR-specific CD4+ T cells permit
      development of these diseases, but the role(s) of the Th1 and Th2 subsets is
      unclear. The STAT4 and STAT6 proteins, which mediate intracellular cytokine
      signaling, are important for differentiation of Th1 and Th2 cells, respectively.
      Wild-type (WT) BALB/c mice, which are prone to develop Th2 rather than Th1
      responses to Ag, are resistant to EMG. We have examined the role of Th1 and Th2
      cells in EMG using STAT4 (STAT4-/-)- or STAT6 (STAT6-/-)-deficient BALB/c mice.
      After AChR immunization, STAT6-/- mice were susceptible to EMG: they developed
      more serum anti-AChR Ab, and had more complement-fixing anti-AChR IgG2a and 2b
      and less IgG1 than WT or STAT4-/- mice. The susceptibility to EMG of STAT6-/-
      mice is most likely related to the Th1 cell-induced synthesis of anti-AChR Ab,
      which trigger complement-mediated destruction of the neuromuscular junction. CD4+
      T cells of the STAT6-/- mice had proliferative responses to the AChR comparable
      to those of WT and STAT4-/- mice, and recognized similar AChR epitopes. STAT6-/-
      mice had abundant AChR-specific Th1 cells, which were nearly absent in WT and
      STAT4-/- mice. Spleen and lymph nodes from STAT6-/- mice contained cells that
      secreted IL-4 when cultured with AChR: these are most likely STAT6-independent
      cells, stimulated in a non-Ag-specific manner by the cytokines secreted by AChR
      specific Th1 cells.

PMID- 14688315
TI  - Activation of resting human primary T cells with chimeric receptors:
      costimulation from CD28, inducible costimulator, CD134, and CD137 in series with
      signals from the TCR zeta chain.
AB  - Chimeric receptors that include CD28 signaling in series with TCRzeta in the same
      receptor have been demonstrated to activate prestimulated human primary T cells
      more efficiently than a receptor providing TCRzeta signaling alone. We examined
      whether this type of receptor can also activate resting human primary T cells,
      and whether molecules other than CD28 could be included in a single chimeric
      receptor in series with TCRzeta to mediate the activation of resting human
      primary T cells. Human CD33-specific chimeric receptors were generated with CD28,
      inducible costimulator, CD134, or CD137 signaling regions in series with TCRzeta
      signaling region and transfected by electroporation into resting human primary T
      cells. Their ability to mediate Ag-specific activation was analyzed in comparison
      with a receptor providing TCRzeta signaling alone. Inclusion of any of the
      costimulatory signaling regions in series with TCRzeta enhanced the level of
      specific Ag-induced IL-2, IFN-gamma, TNF-alpha, and GM-CSF cytokine production
      and enabled resting primary T cells to survive and proliferate in response to Ag
      in the absence of any exogenous factors. Inclusion of CD28, inducible
      costimulator, or CD134 enhanced TCRzeta-mediated, Ag-specific target cell lysis.
      Chimeric receptors providing B7 and TNFR family costimulatory signals in series
      with TCRzeta in the same receptor can confer self-sufficient clonal expansion and
      enhanced effector function to resting human T cells. This type of chimeric
      receptor may now be used to discover the most potent combination of costimulatory
      signals that will improve current immunotherapeutic strategies.

PMID- 14688316
TI  - Up-regulation of Hlx in immature Th cells induces IFN-gamma expression.
AB  - Differentiation of Th cells from naive precursors is a dynamic process that
      involves multiple transcription factors acting at specific time points to
      regulate gene expression. In this study we show that the homeobox transcription
      factor Hlx is up-regulated early in Th1 cell differentiation. Mice constitutively
      expressing an Hlx transgene driven by a CD4 promoter showed marked reduction in
      the CD4+CD8+ thymocyte population. The Hlx transgenic mice generated increased
      numbers of Th1 cells in response to keyhole limpet hemocyanin immunization. After
      differentiation under Th2-polarizing conditions in vitro, the transgenic CD4 T
      cells expressed high levels of IFN-gamma. Intracellular cytokine staining
      revealed that in addition to Th2 cells, large numbers of Th0 and Th1 cells were
      generated from such in vitro differentiated transgenic CD4 T cells. Retrovirally
      overexpressed Hlx also induced the aberrant expression of IFN-gamma in normal CD4
      T cells differentiated under Th2-polarizing conditions. This effect was apparent
      only when Hlx was introduced into the cells by retroviral infection at an early
      time point that led to the expression of the retrovirally transferred Hlx gene at
      a time comparable to that of the up-regulation of the endogenous Hlx during Th1
      cell differentiation. Later infection with Hlx-expressing retrovirus showed no
      effect. Thus, the induction of IFN-gamma expression by Hlx depends on a
      permissive epigenetic state of the IFN-gamma gene locus and/or the molecular
      context of the immature Th cells.

PMID- 14688317
TI  - NK cell TRAIL eliminates immature dendritic cells in vivo and limits dendritic
      cell vaccination efficacy.
AB  - Recent studies have implicated a possible role for NK cells in regulating
      dendritic cells (DC) in vitro. In the present study, we demonstrate that immature
      DC are rapidly eliminated by NK cells in vivo via a pathway dependent on the TNF
      related apoptosis-inducing ligand (TRAIL). Elimination of NK cells and/or
      neutralization of TRAIL function during immunization with immature DC loaded with
      nonself or tumor Ags significantly enhanced T cell responses to these Ags and Ag
      specific tumor immunity. These data suggested that NK cell TRAIL might regulate
      responses to vaccination by controlling the survival of Ag-loaded DC.

PMID- 14688318
TI  - NK cells regulate CD8+ T cell effector function in response to an intracellular
      pathogen.
AB  - We studied the role of NK cells in regulating human CD8+ T cell effector function
      against mononuclear phagocytes infected with the intracellular pathogen
      Mycobacterium tuberculosis. Depletion of NK cells from PBMC of healthy tuberculin
      reactors reduced the frequency of M. tuberculosis-responsive CD8+IFN-gamma+ cells
      and decreased their capacity to lyse M. tuberculosis-infected monocytes. The
      frequency of CD8+ IFN-gamma+ cells was restored by soluble factors produced by
      activated NK cells and was dependent on IFN-gamma, IL-15, and IL-18. M.
      tuberculosis-activated NK cells produced IFN-gamma, activated NK cells stimulated
      infected monocytes to produce IL-15 and IL-18, and production of IL-15 and IL-18
      were inhibited by anti-IFN-gamma. These findings suggest that NK cells maintain
      the frequency of M. tuberculosis-responsive CD8+IFN-gamma+ T cells by producing
      IFN-gamma, which elicits secretion of IL-15 and IL-18 by monocytes. These
      monokines in turn favor expansion of Tc1 CD8+ T cells. The capacity of NK cells
      to prime CD8+ T cells to lyse M. tuberculosis-infected target cells required cell
      cell contact between NK cells and infected monocytes and depended on interactions
      between the CD40 ligand on NK cells and CD40 on infected monocytes. NK cells link
      the innate and the adaptive immune responses by optimizing the capacity of CD8+ T
      cells to produce IFN-gamma and to lyse infected cells, functions that are
      critical for protective immunity against M. tuberculosis and other intracellular
      pathogens.

PMID- 14688319
TI  - APC-independent activation of NK cells by the Toll-like receptor 3 agonist double
      stranded RNA.
AB  - Toll-like receptors (TLRs) play a fundamental role in the recognition of bacteria
      and viruses. TLR3 is activated by viral dsRNA and polyinosinic-polycytidylic acid
      (poly(I:C)), a synthetic mimetic of viral RNA. We show that NK cells, known for
      their capacity to eliminate virally infected cells, express TLR3 and up-regulate
      TLR3 mRNA upon poly(I:C) stimulation. Treatment of highly purified NK cells with
      poly(I:C) significantly augments NK cell-mediated cytotoxicity. Poly(I:C)
      stimulation also leads to up-regulation of activation marker CD69 on NK cells.
      Furthermore, NK cells respond to poly(I:C) by producing proinflammatory cytokines
      like IL-6 and IL-8, as well as the antiviral cytokine IFN-gamma. The induction of
      cytokine production by NK cells was preceded by activation of NF-kappaB. We
      conclude that the ability of NK cells to directly recognize and respond to viral
      products is important in mounting effective antiviral responses.

PMID- 14688320
TI  - Analysis of gene expression and Ig transcription in PU.1/Spi-B-deficient
      progenitor B cell lines.
AB  - A number of presumptive target genes for the Ets-family transcription factor PU.1
      have been identified in the B cell lineage. However, the precise function of PU.1
      in B cells has not been studied because targeted null mutation of the PU.1 gene
      results in a block to lymphomyeloid development at an early developmental stage.
      In this study, we take advantage of recently developed PU.1(-/-)Spi-B(-/-) IL-7
      and stromal cell-dependent progenitor B (pro-B) cell lines to analyze the
      function of PU.1 and Spi-B in B cell development. We show that contrary to
      previously published expectations, PU.1 and/or Spi-B are not required for Ig H
      chain (IgH) gene transcription in pro-B cells. In fact, PU.1(-/-)Spi-B(-/-) pro-B
      cells have increased levels of IgH transcription compared with wild-type pro-B
      cells. In addition, high levels of Igkappa transcription are induced after IL-7
      withdrawal of wild-type or PU.1(-/-)Spi-B(-/-) pro-B cells. In contrast, we found
      that Iglambda transcription is reduced in PU.1(-/-)Spi-B(-/-) pro-B cells
      relative to wild-type pro-B cells after IL-7 withdrawal. These results suggest
      that Iglambda, but not IgH or Igkappa, transcription, is dependent on PU.1 and/or
      Spi-B. The PU.1(-/-)Spi-B(-/-) pro-B cells have other phenotypic changes relative
      to wild-type pro-B cells including increased proliferation, increased CD25
      expression, decreased c-Kit expression, and decreased RAG-1 expression. Taken
      together, our observations suggest that reduction of PU.1 and/or Spi-B activity
      in pro-B cells promotes their differentiation to a stage intermediate between
      late pro-B cells and large pre-B cells.

PMID- 14688321
TI  - Fully functional HLA B27-restricted CD4+ as well as CD8+ T cell responses in TCR
      transgenic mice.
AB  - The strong association of HLA B27 with spondyloarthropathies contrasts strikingly
      with most autoimmune diseases, which are HLA class II associated and thought to
      be mediated by CD4+ T lymphocytes. By introducing a human-derived HLA B27
      restricted TCR into HLA B27 transgenic mice, we have obtained a functional TCR
      transgenic model, GRb, dependent on HLA B27 for response. Surprisingly, HLA B27
      supported CD4+ as well as CD8+ T cell responses in vivo and in vitro. Further,
      HLA B27-restricted CD4+ T cells were capable of differentiation into a range of
      Th1 and Th2 T cell subsets with normal patterns of cytokine expression. The
      transgenic T cells were also able to enhance clearance of recombinant vaccinia
      virus containing influenza nucleoprotein in vivo. This is the first description
      of a human HLA class I-restricted TCR transgenic line. The existence of CD4+ MHC
      class I-restricted T cells has significant implications for immune regulation in
      autoimmunity and, in particular, in HLA B27-associated arthritis. We believe that
      this model provides a novel system for the study of unusual T cell behavior in
      vivo.

PMID- 14688322
TI  - Melanoma-reactive class I-restricted cytotoxic T cell clones are stimulated by
      dendritic cells loaded with synthetic peptides, but fail to respond to dendritic
      cells pulsed with melanoma-derived heat shock proteins in vitro.
AB  - Immunization with heat shock proteins (hsp) isolated from cancer cells has been
      shown to induce a protective antitumor response. The mechanism of hsp-dependent
      cellular immunity has been attributed to a variety of immunological activities
      mediated by hsp. Hsp have been shown to bind antigenic peptides, trim the bound
      peptides by intrinsic enzymatic activity, improve endocytosis of the chaperoned
      peptides by APCs, and enhance the ability of APCs to stimulate peptide-specific T
      cells. We have investigated the potential capacity of hsp70 and gp96 to function
      as a mediator for Ag-specific CTL stimulation in an in vitro model for human
      melanoma. Repetitive stimulation of PBLs by autologous DCs loaded with melanoma
      derived hsp did not increase the frequency of T cells directed against
      immunodominant peptides of melanoma-associated Ags Melan-A and tyrosinase. In
      contrast, repeated T cell stimulation with peptide-pulsed DCs enhanced the number
      of peptide-specific T cells, allowing HLA/peptide multimer-guided T cell cloning.
      We succeeded in demonstrating that the established HLA-A2-restricted CTL clones
      recognized HLA-A2(+) APCs exogenously loaded with the respective melanoma peptide
      as well as melanoma cells processing and presenting these peptides in the context
      of HLA-A2. We were not able to show that these melanoma-reactive CTL clones were
      stimulated by autologous dendritic cells pulsed with melanoma-derived hsp. These
      results are discussed with respect to various models for proving the role of hsp
      in T cell stimulation and to recent findings that part of the immunological
      antitumor activities reported for hsp are independent of the chaperoned peptides.

PMID- 14688323
TI  - A repressor of GATA-mediated negative feedback mechanism of T cell activation.
AB  - The NF-AT family is a group of potent transcription factors that are essential
      for T cell activation in vitro. However, NF-ATc2-deficient Th cells display
      hyperproliferation in response to stimulation, suggesting that NF-ATc2 functions
      as a negative regulator of Th cell activation/proliferation. In this study we
      show that the transcriptional repressor of GATA (ROG) is a direct target gene of
      NF-ATc2 and that NF-ATc2-deficient Th cells are unable to fully up-regulate ROG
      upon stimulation. Restoration of ROG expression in vivo partly corrects the
      hyperproliferation of NF-ATc2-deficient Th cells by attenuating TCR signals. Our
      data, therefore, depict a ROG-mediated negative feedback mechanism of T cell
      activation.

PMID- 14688324
TI  - Tolerogenic APC generate CD8+ T regulatory cells that modulate pulmonary
      interstitial fibrosis.
AB  - Transforming growth factor-beta2-treated Ag-pulsed APC mimic APC from the immune
      privileged eye, and provide signals that generate regulatory T (Tr) cells and
      mediate peripheral tolerance. We postulated that TGF-beta2-treated Ag-pulsed APC
      (tolerogenic APC (tol-APC)) might also orchestrate regulation of immune mediated
      pathogenesis in nonimmune privileged tissues such as the lung. We used an
      adoptive transfer model of autoimmune pulmonary interstitial fibrosis called
      hapten immune pulmonary interstitial fibrosis (ADT-HIPIF) in this study. Mice
      that received 2,4,6-trinitrobenzene sulfonic acid-sensitized cells and challenged
      (intratracheally) with the hapten developed pulmonary interstitial fibrosis.
      However, transfer (i.v.) of TGF-beta2-treated 2,4,6-trinitrobenzene sulfonic acid
      pulsed bone marrow-derived APC (tol-APC) to experimental mice 1 day after
      intratracheal challenge reduced the collagen deposition in the interstitium of
      the lung that usually follows challenge. Furthermore, ADT-HIPIF mice that
      received tol-APC developed Ag-specific efferent CD8+ Tr cells. Adoptive transfer
      of the Tr cells to another set of presensitized mice mediated suppression of the
      efferent phase of Th1 immune response and the subsequent immune dependent
      pulmonary interstitial fibrosis. Thus, tol-APC induced efferent CD8+ Tr cells in
      immune mice, and the regulation of the immune response limited the development of
      autoimmune pulmonary fibrosis in sensitized and pulmonary-challenged mice.
      Because ADT-HIPIF shares etiological and pathological characteristics with a
      variety of human immune inflammatory conditions in the lung that eventuate into
      interstitial fibrosis, these studies provide insight into potential therapy to
      alter the course of pulmonary fibrosis in humans.

PMID- 14688325
TI  - CD1-dependent regulation of chronic central nervous system inflammation in
      experimental autoimmune encephalomyelitis.
AB  - The existence of T cells restricted for the MHC I-like molecule CD1 is well
      established, but the function of these cells is still obscure; one implication is
      that CD1-dependent T cells regulate autoimmunity. In this study, we investigate
      their role in experimental autoimmune encephalomyelitis (EAE), an animal model
      for multiple sclerosis, using CD1-deficient mice on a C57BL/6 background. We show
      that CD1-/- mice develop a clinically more severe and chronic EAE compared with
      CD1+/+ C57BL/6 mice, which was histopathologically confirmed with increased
      demyelination and CNS infiltration in CD1-/- mice. Autoantigen rechallenge in
      vitro revealed similar T cell proliferation in CD+/+ and CD1-/- mice but an
      amplified cytokine response in CD1-/- mice as measured by both the Th1 cytokine
      IFN-gamma and the Th2 cytokine IL-4. Investigation of cytokine production at the
      site of inflammation showed a CNS influx of TGF-beta1-producing cells early in
      the disease in CD1+/+ mice, which was absent in the CD1-/- mice. Passive transfer
      of EAE using an autoreactive T cell line induced equivalent disease in both
      groups, which suggested additional requirements for activation of the CD1
      dependent regulatory pathway(s). When immunized with CFA before T cell transfer,
      the CD1-/- mice again developed an augmented EAE compared with CD1+/+ mice. We
      suggest that CD1 exerts its function during CFA-mediated activation, regulating
      development of EAE both through enhancing TGF-beta1 production and through
      limiting autoreactive T cell activation, but not necessarily via effects on the
      Th1/Th2 balance.

PMID- 14688326
TI  - Cognate B cell signaling via MHC class II: differential regulation of B cell
      antigen receptor and MHC class II/Ig-alpha beta signaling by CD22.
AB  - Recent studies demonstrate that MHC class II molecules can signal via associated
      Ig-alphabeta dimers, signal transducers previously thought to function only in B
      cell Ag receptor (BCR) signaling. Surprisingly, the biologic outputs of MHC class
      II and BCR ligation (by thymus-dependent Ags) differ, e.g., MHC class II
      signaling leads to robust proliferation and extension of pseudopods. It seemed
      possible that these differences might be due, at least in part, to differential
      use of inhibitory coreceptors thought to modulate membrane Ig signals. In this
      study, we demonstrate that CD22, an inhibitory BCR coreceptor, neither associates
      with nor functions in MHC class II/Ig-alphabeta signaling. Interestingly, CD22 is
      actively excluded from cell surface MHC class II aggregates.

PMID- 14688327
TI  - Inducible heat shock protein 70 promotes myelin autoantigen presentation by the
      HLA class II.
AB  - In this study, we investigated the role of the inducible form of heat shock
      protein 70 (hsp70) in the presentation of the major putative autoantigen in
      multiple sclerosis, myelin basic protein (MBP), in the context of appropriate MHC
      class II. By coimmunoprecipitation, we found that MBP is associated with hsp70 in
      APC in an ATP/ADP-dependent manner. Additionally, using confocal microscopy,
      hsp70 was detected in the endocytic pathway of APC, where it colocalized with MBP
      and HLA-DR. The immunodominant epitopes of MBP 85-99 and 80-99 were shown to bind
      selectively and specifically to hsp70 by surface plasmon resonance. The
      functional significance of MBP interaction with hsp70 was demonstrated by the
      detection of enhanced responses of an MBP-specific T cell hybridoma to MBP and
      MBP 80-99 with increasing levels of hsp70 and reduced responses when hsp70
      expression was diminished within APC-expressing DRA*0101, DRB1*1501 (DR1501).
      However, when MBP 85-99 was used as the stimulus, T cell hybridoma responses were
      not enhanced by hsp70 overexpression within APC, suggesting that hsp70
      contributes to Ag processing rather than Ag presentation. The importance of a
      direct association between MBP and hsp70 in the presentation pathways was
      demonstrated by enhanced efficacy of MBP presentation by APC transfected with a
      plasmid vector encoding a fusion hsp70-MBP protein. This is the first report on
      the involvement of self-inducible hsp70 in MHC class II-dependent autoantigen
      processing by APC. It implicates that aberrant self hsp expression may lead to
      the enhancement/modulation of autoimmune responses.

PMID- 14688328
TI  - Regulation of CD103 expression by CD8+ T cells responding to renal allografts.
AB  - CD103 is an integrin with specificity for the epithelial cell-specific ligand, E
      cadherin. Recent studies indicate that CD103 expression endows peripheral CD8
      cells with a unique capacity to access the epithelial compartments of organ
      allografts. In the present study we used a nonvascularized mouse renal allograft
      model to 1) define the mechanisms regulating CD103 expression by graft
      infiltrating CD8 effector populations, and 2) identify the cellular compartments
      in which this occurs. We report that CD8 cells responding to donor alloantigens
      in host lymphoid compartments do not initially express CD103, but dramatically up
      regulate CD103 expression to high levels subsequent to migration to the graft
      site. CD103+CD8+ cells that infiltrated renal allografts exhibited a classic
      effector phenotype and were selectively localized to the graft site. CD8 cells
      expressing low levels of CD103 were also present in lymphoid compartments, but
      three-color analyses revealed that these are almost exclusively of naive
      phenotype. Adoptive transfer studies using TCR-transgenic CD8 cells demonstrated
      that donor-specific CD8 cells rapidly and uniformly up-regulate CD103 expression
      following entry into the graft site. Donor-specific CD8 cells expressing a
      dominant negative TGF-beta receptor were highly deficient in CD103 expression
      following migration to the graft, thereby implicating TGF-beta activity as a
      dominant controlling factor. The relevance of these data to conventional
      (vascularized) renal transplantation is confirmed. These data support a model in
      which TGF-beta activity present locally at the graft site plays a critical role
      in regulating CD103 expression, and hence the epitheliotropism, of CD8 effector
      populations that infiltrate renal allografts.

PMID- 14688329
TI  - Superantigen stimulation reveals the contribution of Lck to negative regulation
      of T cell activation.
AB  - The conventional paradigm of T cell activation through the TCR states that Lck
      plays a critical activating role in this signaling process. However, the T cell
      response to bacterial superantigens does not require Lck. In this study we report
      that not only is Lck dispensable for T cell activation by superantigens, but it
      actively inhibits this signaling pathway. Disruption of Lck function, either by
      repression of Lck gene expression or by selective pharmacologic inhibitors of
      Lck, led to increased IL-2 production in response to superantigen stimulation.
      This negative regulatory effect of Lck on superantigen-induced T cell responses
      required the kinase activity of Lck and correlated with early TCR signaling, but
      was independent of immunological synapse formation and TCR internalization. Our
      data demonstrate that the multistage role of Lck in T cell signaling includes the
      activation of a negative regulatory pathway of T cell activation.

PMID- 14688330
TI  - Role of TNF receptor-associated factor 3 in the CD40 signaling by production of
      reactive oxygen species through association with p40phox, a cytosolic subunit of
      nicotinamide adenine dinucleotide phosphate oxidase.
AB  - To extend our previous report, which showed the production of the reactive oxygen
      species (ROS) after the CD40 ligation in the B cells, we further examined the
      possible mechanisms for ROS production and the involvement of CD40-induced ROS in
      p38 activation. Our research shows that the stimulation of WEHI 231 B lymphomas
      with anti-CD40 induced ROS production and p38 activation. An antioxidant N-acetyl
      L-cysteine or an inhibitor for NADPH oxidase blocked both of these, but the
      inhibitors for 5-lipoxygenase did not. We also show that the treatment of cells
      with inhibitors for the phosphatidylinositol 3-kinase (PI3-K) interfered with the
      CD40-induced ROS production and p38 activation. In addition, when overexpressed
      with a dominant negative form of either Rac1 (N17Rac1) or the TNFR-associated
      factor (TRAF) 3, the WEHI 231 B cells did not show a full response to the CD40
      stimulation to produce ROS. Molecular association studies further revealed that
      the TRAF3 association with p40(phox), a cytosolic subunit of NADPH oxidase and
      p85 (a subunit of PI3-K), may possibly be responsible for the production of ROS
      by CD40 stimulation in WEHI 231 B cells. Collectively, these data suggest that
      the CD40-induced ROS production by NADPH oxidase in WEHI 231 requires the role of
      TRAF3, as well as activities of PI3-K and Rac1.

PMID- 14688331
TI  - Effects of T cell frequency and graft size on transplant outcome in mice.
AB  - The features that determine whether graft-reactive T lymphocytes develop into
      effector cells capable of mediating organ destruction are not well understood. To
      investigate potential factors involved in this process, we first confirmed that
      female recipient mice acutely rejected minor Ag-disparate male skin, but not
      heart transplants. Despite this difference in outcome, heart and skin
      transplantation induced antidonor T cell responses of similar magnitude,
      specificity, and cytokine profile. The heart-graft-primed T cells transiently
      infiltrated the graft and ultimately induced the development of chronic
      transplant vasculopathy. Increasing the frequency of donor-reactive T cells by
      presensitization or by using TCR (CD8+ antimale)-transgenic recipients did not
      mediate acute rejection but accelerated the pace and severity of the
      vasculopathy. Surprisingly, decreasing the tissue mass of the donor heart by 50%
      resulted in acute rejection of these smaller grafts without increasing the
      frequency of antidonor effector T cells in the recipients. In complementary
      studies, placement of one or two male skin grafts on a single recipient did not
      affect the frequency or cytokine profile of the induced antimale T cell
      repertoire. Nonetheless, the recipients of single grafts acutely rejected the
      transplanted skin while the recipients of two skin grafts did not. These results
      provide new insight into the pathogenesis of transplant vasculopathy and provide
      an explanation for the difference in outcome between murine skin and heart
      transplants by highlighting the novel concept that the efficiency of transplant
      reactive T cell immunity is heavily influenced by the tissue burden it encounters
      at the effector stage.

PMID- 14688332
TI  - T cell clonal conditioning: a phase occurring early after antigen presentation
      but before clonal expansion is impacted by Toll-like receptor stimulation.
AB  - After in vivo immunization, Ag-specific T cells disappear from circulation and
      become sequestered in lymphoid tissue where they encounter Ag presented by
      dendritic cells. In the same site and just after Ag presentation, they
      "disappear" a second time and we investigated this process. Using a mouse model
      of T cell deletion (without Toll-like receptor (TLR) stimulation) vs survival
      (with TLR stimulation), Ag-specific T cells indeed became undetectable by flow
      cytometry, however were readily detected by immunohistochemistry. Thus, whether
      or not the activated T cells were destined to delete or survive, they were
      difficult to extract from lymphoid tissue and did not disappear but in fact were
      abundantly present. Nevertheless, profound differences were observed during this
      time period when tolerizing conditions were compared with immunizing conditions.
      TLR stimulation induced an increase in CD25 expression, acquisition of surface
      MHC class II, and abnormally high increases in forward and side scatter of the
      peptide-specific T cells. Using a modified adoptive transfer approach, we
      demonstrated by flow cytometry that in the presence of TLR stimulation the Ag
      specific T cells were tightly coupled to dendritic cells, explaining the unusual
      increases in size and granularity. Ultimately, these events induced the specific
      T cells to differentiate into memory cells. We postulate that this is a stage
      where T cells are either conditioned to survive or to delete depending upon the
      activation status of the innate immune system.

PMID- 14688333
TI  - Human intestinal fibroblasts prevent apoptosis in human intestinal mast cells by
      a mechanism independent of stem cell factor, IL-3, IL-4, and nerve growth factor.
AB  - In rodents, fibroblasts (FBs) mediate stem cell factor (SCF)-dependent growth of
      mast cells (MCs). In humans, SCF is mandatory for MC differentiation and
      survival. Other factors such as IL-3, IL-4, and nerve growth factor (NGF) act in
      synergism with SCF, thus enhancing proliferation and/or preventing apoptosis in
      MCs. In this study, we studied in vitro interactions between human MCs and human
      FBs, both isolated from the intestine and purified to homogeneity. In coculture
      with FBs, MCs survived for up to 3 wk, whereas purified MCs cultured alone died
      within a few days. TNF-alpha and IL-1beta, which both did not affect MC survival
      directly, enhanced FB-dependent MC growth. We provide evidence that FB-derived MC
      growth factors are soluble, heat-sensitive molecules which down-regulate MC
      apoptosis without enhancing MC proliferation. However, only low amounts of SCF
      were measured in FB-conditioned medium (<0.2 ng/ml). Moreover, blocking of SCF/c
      kit interaction by anti-SCF or anti-c-kit Abs and neutralization of IL-3, IL-4,
      and NGF did not affect MC survival in the coculture system. In conclusion, our
      data indicate that human FBs promote survival of human MCs by mechanisms
      independent of SCF, IL-3, IL-4, and NGF. Such interactions between MCs and FBs
      may explain why MCs accumulate at sites of inflammatory bowel disease and
      intestinal fibrosis.

PMID- 14688334
TI  - CXCR1+CD4+ T cells in human allergic disease.
AB  - Chemokine receptors play an important role in the migration of leukocytes to
      sites of allergic inflammation in humans. In this study, we have identified
      increased expression of the chemokine receptor CXCR1 on CD4+ T lymphocytes
      derived from patients with atopic disease compared with normal donors. Enhanced
      expression of CXCR1 by atopic donors was identified on freshly isolated
      peripheral blood cells and on expanded cell populations derived from nasal
      mucosal biopsies and from the periphery. Identification of CXCR1 expression on
      CD4 cells in the nasal mucosa was confirmed by double immunofluorescence. In
      addition, expression of CXCR1 was dramatically decreased in patients undergoing
      successful treatment of allergic rhinitis by specific immunotherapy. CXCR1
      provided a functional receptor capable of regulating T cells in the context of
      allergic disease, since expression of CXC chemokine ligand 8 was up-regulated at
      the site of allergic inflammation and freshly isolated CXCR1+CD4+ cells from
      atopic donors showed an enhanced functional response to this ligand. CXCR1
      expression on CD4+ T cells was increased in vitro in response to the pro-Th2
      cytokine IL-4. Phenotypic analysis reveals that IFN-gamma expression was lower in
      the CXCR1+CD4+ cells. The identification of CXCR1 as a marker of allergic
      rhinitis reveals a possible target for therapeutic intervention in atopic
      disease.

PMID- 14688335
TI  - Colorectal cancer cells induce lymphocyte apoptosis by an endothelial monocyte
      activating polypeptide-II-dependent mechanism.
AB  - Endothelial monocyte-activating polypeptide-II (EMAP-II) was first isolated from
      cell growth medium conditioned by tumor cells, and is closely related or
      identical with the p43 component of the mammalian multisynthase complex. In its
      secreted form, EMAP-II has multiple cytokine-like activities in vitro, inducing
      procoagulant activity on the surface of endothelial cells, increasing expression
      of E- and P-selectins and TNF-R1, and directing migration of monocytes and
      neutrophils. EMAP-II has also been shown to induce apoptosis in endothelial
      cells, leading to the suggestion that it is a proinflammatory polypeptide with
      antiangiogenic activity. The role of secreted EMAP-II in tumors remains poorly
      understood, and we hypothesized that EMAP-II may play a role in immune evasion by
      tumor cells. We investigated its effects on lymphocytes, using recombinant
      protein, or colorectal cancer cell lines, as a source of native EMAP-II.
      Recombinant EMAP-II inhibits DNA synthesis and cell division, and induces
      apoptosis in mitogen-activated lymphocytes in PBMC preparations, and in Jurkat T
      cells. Native EMAP-II, released by or expressed on the surface of colorectal
      carcinoma cells, also induces activation of caspase 8 and apoptosis of PBLs and
      Jurkat cells, which are partially blocked by addition of Abs against EMAP-II.
      Thus, activated lymphocytes, along with proliferating endothelial cells, are
      targets for the cytotoxic activity of EMAP-II. Membrane-bound and soluble EMAP-II
      appear to play multiple roles in the tumor microenvironment, one of which is to
      assist in immune evasion.

PMID- 14688336
TI  - The alpha 1 beta 1 and alpha E beta 7 integrins define a subset of dendritic
      cells in peripheral lymph nodes with unique adhesive and antigen uptake
      properties.
AB  - Dendritic cells (DCs) are a heterogeneous population of APCs with critical roles
      in T cell activation and immune regulation. We report in this study the
      identification and characterization of a novel subset of DCs resident in skin
      draining peripheral lymph nodes of normal mice. This subset of
      CD11c(high)CD40(high)CD8alpha(intermediate (int)) DCs expresses the collagen
      binding integrin, alpha1beta1, and the E-cadherin-binding integrin, alphaEbeta7.
      Although alpha1beta1 and alphaEbeta7 are also expressed on
      CD11c(high)CD40(int)CD8alpha(high) lymphoid DCs,
      CD11c(high)CD40(high)CD8alpha(int) DCs demonstrate preferential integrin-mediated
      adhesion to collagen and fibronectin. This DC subset most likely acquires
      expression of these integrins in peripheral lymph node, as this subset is not
      found in the spleen or mesenteric lymph node, and recent DC migrants from the
      skin lack expression of alpha1beta1 and alphaEbeta7 integrins. Resident
      CD40(high) DCs express alpha1beta1 integrin and colocalize with collagen in lymph
      nodes. When compared with CD11c(high)CD40(high)CD8alpha(int) DCs lacking
      expression of these integrins, the alpha1beta1+alphaEbeta7+DC subset exhibits
      more efficient formation of Ag-independent conjugates with T cells, and a
      decreased ability to acquire soluble Ag. Thus, the alpha1beta1 and alphaEbeta7
      integrins define a unique population of peripheral lymph node-derived DCs with
      altered functional properties and adhesive potential that localizes these cells
      to sites in lymph nodes where Ag presentation to T cells occurs.

PMID- 14688337
TI  - Dendritic cell maturation controls adhesion, synapse formation, and the duration
      of the interactions with naive T lymphocytes.
AB  - The initiation of adaptive immune responses requires the direct interaction of
      dendritic cells (DCs) with naive T lymphocytes. It is well established that the
      maturation state of DCs has a critical impact on the outcome of the response. We
      show here that mature DCs form stable conjugates with naive T cells and induce
      the formation of organized immune synapses. Immature DCs, in contrast, form few
      stable conjugates with no organized immune synapses. A dynamic analysis revealed
      that mature DCs can form long-lasting interactions with naive T cells, even in
      the absence of Ag. Immature DCs, in contrast, established only short intermittent
      contacts, suggesting that the premature termination of the interaction prevents
      the formation of organized immune synapses and full T cell activation.

PMID- 14688338
TI  - Dermal enhancement: bacterial products on intact skin induce and augment organ
      specific autoimmune disease.
AB  - The skin is both an essential barrier for host defense and an important organ of
      immunity. In this study, we show that the application of cholera toxin to intact
      mouse skin induces and enhances autoimmune diseases affecting organs at distant
      anatomic sites, whereas its administration by the mucosal route has been reported
      to have the opposite effect. First, the CNS autoantigen myelin oligodendrocyte
      glycoprotein 35-55, when applied repeatedly with cholera toxin to the intact skin
      of healthy C57BL/6 mice, induced relapsing paralysis with demyelinating
      immunopathologic features similar to multiple sclerosis. Second, the application
      of cholera toxin in the absence of autoantigen exacerbated the severity of
      conventional experimental autoimmune encephalomyelitis induced by myelin
      oligodendrocyte glycoprotein in CFA. Third, the application of cholera toxin to
      the intact skin of NOD/Lt mice, with or without insulin B peptide 9-23,
      exacerbated insulitis and T lymphocyte-derived IFN-gamma and IL-4 production in
      the islets of Langerhans, resulting in an increased incidence and rate of onset
      of autoimmune diabetes. The data presented in this study highlight the different
      outcomes of adjuvant administration by different routes. Because dermal
      application of cholera toxin, and other bacterial products with similar adjuvant
      activities, is being developed as a clinical vaccination strategy, these data
      raise the possibility that it could precipitate autoimmune disease in genetically
      susceptible humans.

PMID- 14688339
TI  - Pulmonary tumors inefficiently prime tumor-specific T cells.
AB  - The lung is a common site of metastatic and primary tumor growth, and has been
      shown to be an immunosuppressive environment. We tested the impact of the lung
      environment on the development of tumor-specific T cell responses against the
      CMS5 fibrosarcoma, and found a deficit in the efficacy of naive tumor-specific
      DUC18 T cells against tumors established in the lung. One hundred-fold more naive
      tumor-specific T cells were required to protect against tumor development or
      reject established tumors in the lung than an identical tumor challenge delivered
      s.c. in the flank. Importantly, CMS5 growing in the flank facilitated the
      rejection of tumors present in the lungs. In the presence of flank tumors,
      transferred T cells were not phenotypically altered but were present in much
      greater numbers in the parabronchial lymph nodes, bronchoalveolar lavage, and
      lung parenchyma than in mice bearing lung tumors alone. We hypothesized that APC
      present in the lung and skin draining lymph nodes were differentially initiating
      T cell proliferation, leading to differences in the size of the final effector
      populations. A direct comparison of DUC18 T cell proliferation against APC from
      flank or lung draining lymph nodes showed profoundly greater proliferation to
      flank draining lymph node APC. The impaired stimulation of naive T cell
      proliferation by lung draining APC provides one mechanistic explanation for the
      lower overall immune response, and inability to effectively reject tumors, in the
      lung.

PMID- 14688340
TI  - Dexamethasone inhibits IL-12p40 production in lipopolysaccharide-stimulated human
      monocytic cells by down-regulating the activity of c-Jun N-terminal kinase, the
      activation protein-1, and NF-kappa B transcription factors.
AB  - IL-12 plays a critical role in the development of cell-mediated immune responses
      and in the pathogenesis of inflammatory and autoimmune disorders. Dexamethasone
      (DXM), an anti-inflammatory glucocorticoid, has been shown to inhibit IL-12p40
      production in LPS-stimulated monocytic cells. In this study, we investigated the
      molecular mechanism by which DXM inhibits IL-12p40 production by studying the
      role of the mitogen-activated protein kinases (MAPKs), and the key transcription
      factors involved in human IL-12p40 production in LPS-stimulated monocytic cells.
      A role for c-Jun N-terminal kinase (JNK) MAPK in LPS-induced IL-12p40 regulation
      in a promonocytic THP-1/CD14 cell line was demonstrated by using specific
      inhibitors of JNK activation, SP600125 and a dominant-negative stress-activated
      protein/extracellular signal-regulated kinase kinase-1 mutant. To identify
      transcription factors regulating IL-12p40 gene transcription, extensive deletion
      analyses of the IL-12p40 promoter was performed. The results revealed the
      involvement of a sequence encompassing the AP-1-binding site, in addition to that
      of NF-kappaB. The role of AP-1 in IL-12p40 transcription was confirmed by using
      antisense c-fos and c-jun oligonucleotides. Studies conducted to understand the
      regulation of AP-1 and NF-kappaB activation by JNK MAPK revealed that both DXM
      and SP600125 inhibited IL-12p40 gene transcription by inhibiting the activation
      of AP-1 and NF-kappaB transcription factors as revealed by luciferase reporter
      and gel mobility shift assays. Taken together, our results suggest that DXM may
      inhibit IL-12p40 production in LPS-stimulated human monocytic cells by down
      regulating the activation of JNK MAPK, the AP-1, and NF-kappaB transcription
      factors.

PMID- 14688341
TI  - Two distinct waves of membrane-proximal B cell antigen receptor signaling
      differentially regulated by Src homology 2-containing inositol polyphosphate 5
      phosphatase.
AB  - The phosphatidylinositol 3-kinase (PI3K) pathway plays a critical role in B cell
      activation and differentiation. Recruitment of pleckstrin homology (PH) domain
      containing signal transduction proteins to the plasma membrane through binding to
      3-phosphoinositide second messengers represents a major effector mechanism for
      PI3Ks. We have found that the PH domains of Bam32 and tandem PH domain-containing
      protein 2 (TAPP2) specify a temporally distinct wave of membrane recruitment
      compared with that of Bruton's tyrosine kinase (Btk), with recruitment of these
      two adaptors representing a later stage of the response. In this study we provide
      direct evidence that PH domain-dependent recruitment of Btk to the membrane is
      blocked by coligation of the inhibitory receptor FcgammaRII in human B lymphoma
      cells. In contrast, recruitment specified by the Bam32 or TAPP2 PH domains is
      completely insensitive to FcgammaRII inhibition. This differential regulation can
      be accounted for by Src homology 2-containing inositol polyphosphate 5
      phosphatase (SHIP) activity alone, as expression of membrane-targeted SHIP
      completely abrogated Btk recruitment, but had no inhibitory effect on Bam32 or
      TAPP2 recruitment. Strikingly, kinetic analysis revealed that membrane
      recruitment of Bam32 and TAPP2 is actually more rapid under "inhibitory"
      signaling conditions. Analysis of 3-phosphoinositide generation under activating
      and inhibitory signaling conditions indicated that recruitment of Bam32 and TAPP2
      is inversely correlated with the SHIP substrate/product ratio
      (phosphatidylinositol 3,4,5-trisphosphate/phosphatidylinositol 3,4-bisphosphate).
      Overexpression of TAPP2 in B cells led to an increase in the sustained phase of
      the calcium response and increased NF-AT-dependent transcriptional activation
      after B cell Ag receptor ligation. Together, these results suggest that Bam32 and
      TAPP2 adaptors define a novel group of SHIP-activated targets of PI3K that
      regulate B cell Ag receptor signaling.

PMID- 14688342
TI  - Partitioning of rearranged Ig genes by mutation analysis demonstrates D-D fusion
      and V gene replacement in the expressed human repertoire.
AB  - The accurate partitioning of Ig H chain V(H)DJ(H) junctions and L chain V(L)J(L)
      junctions is problematic. We have developed a statistical approach for the
      partitioning of such sequences, by analyzing the distribution of point mutations
      between a determined V gene segment and putative Ig regions. The establishment of
      objective criteria for the partitioning of sequences between V(H), D, and J(H)
      gene segments has allowed us to more carefully analyze intervening putative
      nontemplated (N) nucleotides. An analysis of 225 IgM H chain sequences, with five
      or fewer V mutations, led to the alignment of 199 sequences. Only 5.0% of
      sequences lacked N nucleotides at the V(H)D junction (N1), and 10.6% at the DJ(H)
      junction (N2). Long N regions (>9 nt) were seen in 20.6% of N1 regions and 17.1%
      of N2 regions. Using a statistical analysis based upon known features of N
      addition, and mutation analysis, two of these N regions aligned with D gene
      segments, and a third aligned with an inverted D gene segment. Nine additional
      sequences included possible alignments with a second D segment. Four of the
      remaining 40 long N1 regions included 5' sequences having six or more matches to
      V gene end motifs, which may be the result of V gene replacement. Such sequences
      were not seen in long N2 regions. The long N regions frequently seen in the
      expressed repertoire of human Ig gene rearrangements can therefore only partly be
      explained by V gene replacement and D-D fusion.

PMID- 14688343
TI  - A functional C5a anaphylatoxin receptor in a teleost species.
AB  - The anaphylatoxins are potent, complement-derived low m.w. proteins that bind to
      specific seven-transmembrane receptors to elicit and amplify a variety of
      inflammatory reactions. C5a is the most potent of these phlogistic peptides and
      is a strong chemoattractant for neutrophils and macrophages/monocytes. Although
      lower vertebrates possess complement systems that are believed to function
      similarly to those of mammals, anaphylatoxin receptors have not previously been
      characterized in any nonmammalian vertebrate. To study the functions of C5a in
      teleost fish, we generated recombinant C5a of the rainbow trout, Oncorhynchus
      mykiss (tC5a), and used fluoresceinated tC5a (tC5aF) and flow cytometry to
      identify the C5a receptor (C5aR) on trout leukocytes. Granulocytes/Macrophages
      present in cell suspensions of the head kidney (HKL), the main hemopoietic organ
      in teleosts, showed a univariate type of receptor expression, whereas those from
      the peripheral blood demonstrated either a low or high level of expression. The
      binding of tC5aF was inhibited by excess amounts of unlabeled tC5a or
      tC5a(desArg), demonstrating that sites other than the C-terminal of tC5a interact
      with the C5aR. Both tC5a and tC5a(desArg) were able to induce chemotactic
      responses in granulocytes in a concentration-dependent manner, but the desArg
      derivative was at least 10-fold less active. Homologous desensitization occurred
      after HKL were exposed to continuous or high concentrations of tC5a, with a loss
      of tC5aF binding and an 80% reduction in chemotactic responses toward tC5a.
      Pertussis toxin reduced the migration of HKL toward tC5a by 40%, suggesting only
      a partial involvement of pertussis toxin-sensitive G(i) proteins in tC5a-mediated
      chemotaxis.

PMID- 14688344
TI  - Domain shuffling has been the main mechanism forming new hominoid killer cell Ig
      like receptors.
AB  - The killer cell Ig-like receptor (KIR) gene family encodes MHC class I-specific
      receptors, which regulate NK cell responses and are also expressed on
      subpopulations of T cells. KIR haplotypes vary in gene content, which, in
      combination with allelic polymorphism, extensively diversifies the KIR genotype
      both within and between human populations. Species comparison indicates that
      formation of new KIR genes and loss of old ones are frequent events, so that few
      genes are conserved even between closely related species. In this regard, the
      hominoids define a time frame that is particularly informative for understanding
      the processes of KIR evolution and its potential impact on killer cell biology.
      KIR cDNA were characterized from PBMC of three gorillas, and genomic DNA were
      characterized for six additional individuals. Eleven gorilla KIR genes were
      defined. With attainment of these data, a set of 75 KIR sequences representing
      five hominoid species was assembled, which also included rhesus monkey, cattle,
      and rodent KIR. Searching this data set for recombination events, and
      phylogenetic analysis using Bayesian methods, demonstrated that new KIR were
      usually the result of recombination between loci in which complete protein
      domains were shuffled. Further phylogenetic analysis of the KIR sequences after
      removal of confounding recombined segments showed that only two KIR genes,
      KIR2DL4 and KIR2DL5, have been preserved throughout hominoid evolution, and one
      of them, KIR2DL4, is also common to rhesus monkey and hominoids. Other KIR genes
      represent recombinant forms present in a minority of species, often only one, as
      exemplified by 8 of the 11 gorilla KIR genes.

PMID- 14688345
TI  - The tetraspanin CD81 is necessary for partitioning of coligated CD19/CD21-B cell
      antigen receptor complexes into signaling-active lipid rafts.
AB  - Tetraspanins have been hypothesized to facilitate the organization of functional
      multimolecular membrane complexes. In B cells the tetraspanin CD81 is a component
      of the CD19/CD21 complex. When coligated to the B cell Ag receptor (BCR), the
      CD19/CD21 complex significantly enhances BCR signaling in part by prolonging the
      association of the BCR with signaling-active lipid rafts. In this study CD81 is
      shown to associate with lipid rafts upon coligation of the BCR and the CD19/CD21
      complex. Using B cells from CD81-deficient mice we demonstrate that in the
      absence of CD81, coligated BCR and CD19/CD21 complexes fail to partition into
      lipid rafts and enhance BCR signaling from rafts. Furthermore, a chimeric CD19
      protein that associates only weakly if at all with CD81 fails to promote the
      association of coligated BCR with lipid rafts. The requirement for CD81 to
      promote lipid raft association may define a novel mechanism by which tetraspanins
      function as molecular facilitators of signaling receptors.

PMID- 14688346
TI  - Molecular characterization of a putative antiretroviral transcriptional factor,
      OTK18.
AB  - Elucidation of the factors involved in host defense against human
      immunodeficiency viral infection remains pivotal if viral control may be
      achieved. Toward these ends, we investigated the function of a putative
      antiretroviral factor, OTK18, isolated by differential display of mRNA from HIV
      type 1-infected primary human monocyte-derived macrophages. Molecular and
      immunohistochemical analyses showed that the OTK18 nucleotide sequence contains
      13 adjacent C(2)H(2)-type zinc finger motifs, a Kruppel-associated box, and is
      localized to both cytosol and nucleus. Mutational analyses revealed that both the
      Kruppel-associated box and zinc finger regions of OTK18 are responsible for the
      transcriptional suppressive activities of this gene. OTK18 was copiously
      expressed in macrophages following HIV type I infection and diminished progeny
      virion production. A mechanism for this antiretroviral activity was by
      suppression of HIV type 1 Tat-induced viral long terminal repeat promoter
      activity. Our findings suggest that one possible function of OTK18 is as a HIV
      type 1-inducible transcriptional suppressor.

PMID- 14688347
TI  - Herpes simplex virus-specific CD8+ T cells can clear established lytic infections
      from skin and nerves and can partially limit the early spread of virus after
      cutaneous inoculation.
AB  - HSV infects skin or mucosal epithelium as well as entering the sensory nerves and
      ganglia. We have used TCR-transgenic T cells specific for the immunodominant
      class I-restricted determinant from HSV glycoprotein B (gB) combined with a flank
      zosteriform model of infection to examine the ability of CD8+ T cells to deal
      with infection. During the course of zosteriform disease, virus rapidly spreads
      from the primary inoculation site in the skin to sensory dorsal root ganglia and
      subsequently reappears in the distal flank. Virus begins to be cleared from all
      sites about 5 days after infection when gB-specific CD8+ T cells first appear
      within infected tissues. Although activated gB-specific effectors can partially
      limit virus egress from the skin, they do so only at the earliest times after
      infection and are ineffective at halting the progression of zosteriform disease
      once virus has left the inoculation site. In contrast, these same T cells can
      completely clear ongoing lytic replication if transferred into infected
      immunocompromised RAG-1-/- mice. Therefore, we propose that the role of CD8+ T
      cells during the normal course of disease is to clear replicating virus after
      infection is well established rather than limit the initial spread of HSV from
      the primary site of inoculation.

PMID- 14688348
TI  - Essential contribution of monocyte chemoattractant protein-1/C-C chemokine ligand
      2 to resolution and repair processes in acute bacterial pneumonia.
AB  - Neutrophil infiltration is the first step in eradication of bacterial infection,
      but neutrophils rapidly die after killing bacteria. Subsequent accumulation of
      macrophage lineage cells, such as alveolar macrophages (AMs), is essential to
      remove dying neutrophils, which are a source of injurious substances. Macrophage
      lineage cells can promote tissue repair, by producing potential growth factors
      including hepatocyte growth factor (HGF). However, it remains elusive which
      factor activates macrophage in these processes. Intratracheal instillation of
      Pseudomonas aeruginosa caused neutrophil infiltration in the airspace;
      subsequently, the numbers of total AMs and neutrophil ingested AMs were
      increased. Bronchoalveolar lavage (BAL) fluid levels of monocyte chemoattractant
      protein (MCP)-1/CC chemokine ligand-2 (CCL2), a potent macrophage-activating
      factor, were increased before the increases in the number of AM ingesting
      neutrophils and HGF levels in BAL fluid. Immunoreactive MCP-1 proteins were
      detected in alveolar type II epithelial cells and AMs only after P. aeruginosa
      infection. The administration of anti-MCP-1/CCL2 Abs reduced the increases in the
      number of AM-ingesting neutrophils and HGF levels in BAL fluid, and eventually
      aggravated lung tissue injury. In contrast, the administration of MCP-1/CCL2
      enhanced the increases in the number of AM ingesting neutrophils and HGF levels
      in BAL fluid, and eventually attenuated lung tissue injury. Furthermore, MCP
      1/CCL2 enhanced the ingestion of apoptotic neutrophils and HGF production by a
      mouse macrophage cell line, RAW 267.4, in a dose-dependent manner. Collectively,
      MCP-1/CCL2 has a crucial role in the resolution and repair processes of acute
      bacterial pneumonia by enhancing the removal of dying neutrophils and HGF
      production by AMs.

PMID- 14688349
TI  - Actinobacillus actinomycetemcomitans cytolethal distending toxin (Cdt): evidence
      that the holotoxin is composed of three subunits: CdtA, CdtB, and CdtC.
AB  - We have shown the Actinobacillus actinomycetemcomitans produces an
      immunosuppressive factor encoded by the cytolethal distending toxin (cdt)B gene,
      which is homologous to a family of Cdts expressed by several Gram-negative
      bacteria. We now report that the capacity for CdtB to induce G(2) arrest in
      Jurkat cells is greater in the presence of the other Cdt peptides: CdtA and CdtC.
      Plasmids containing the cdt operon were constructed and expressed in Escherichia
      coli; each plasmid contained a modified cdt gene that expressed a Cdt peptide
      containing a C-terminal His tag. All three Cdt peptides copurified with the His
      tagged Cdt peptide. Each of the peptides associated with the complex was
      truncated; N-terminal amino acid analysis of CdtB and CdtC indicated that the
      truncation corresponds to cleavage of a previously described signal sequence.
      CdtA was present in two forms in crude extracts, 25 and 18 kDa; only the 18-kDa
      fragment copurified with the Cdt complexes. Cdt complexes were also
      immunoprecipitated from A. actinomycetemcomitans extracts using anti-CdtC mAb.
      Exposure of Jurkat cells to 40 pg resulted in >50% accumulation of G(2) cells.
      CdtB and CdtC were detected by immunofluorescence on the cell surface after 2-h
      exposure to the holotoxin. CdtA was not detected by immunofluorescence, but all
      three peptides were associated with Jurkat cells when analyzed by Western blot.
      These studies suggest that the active Cdt holotoxin is a heterotrimer composed of
      truncated CdtA, CdtB, and CdtC, and all three peptides appear to associate with
      lymphocytes.

PMID- 14688350
TI  - Localization of cystic fibrosis transmembrane conductance regulator to lipid
      rafts of epithelial cells is required for Pseudomonas aeruginosa-induced cellular
      activation.
AB  - The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein is an
      epithelial cell receptor for the outer core oligosaccharide of the Pseudomonas
      aeruginosa LPS. Bacterial binding leads to CFTR-dependent bacterial
      internalization, initiation of NF-kappaB nuclear translocation, cellular
      desquamation, and eventual apoptosis of the infected cells, all of which are
      critical for innate immune resistance to infection with this pathogen. Lack of
      this reaction in CF patients underlies their hypersusceptibility to chronic P.
      aeruginosa infection. In this study we tested whether these epithelial cell
      responses are dependent upon the localization of CFTR to lipid rafts. Confocal
      microscopy showed that green fluorescent protein-tagged CFTR (GFP-CFTR) and the
      lipid raft marker ganglioside GM1 colocalized at sites of P. aeruginosa contact
      and internalization. GFP-CFTR localized to low density Triton X-100-insoluble
      fractions in lysates of Madin-Darby canine kidney GFP-CFTR cells, and P.
      aeruginosa infection increased the levels of GFP-CFTR in these fractions as
      determined by Western blot. Cells expressing GFP-DeltaF508-CFTR did not have
      rafts with detectable CFTR protein. Extraction of cell surface cholesterol via
      cyclodextrin treatment of the cells inhibited CFTR entry into rafts. In addition,
      cyclodextrin treatment of both human and canine epithelial cells inhibited
      cellular ingestion of P. aeruginosa, NF-kappaB nuclear translocation, and
      apoptosis. These results indicate that lipid raft localization of CFTR is
      required for signaling in response to P. aeruginosa infection. Such signaling is
      needed for the coordination of innate immunity to P. aeruginosa lung infection, a
      process that is defective in CF.

PMID- 14688351
TI  - Organism-specific neutrophil-endothelial cell interactions in response to
      Escherichia coli, Streptococcus pneumoniae, and Staphylococcus aureus.
AB  - The recruitment of polymorphonuclear leukocytes (PMNs) from the vascular space
      into the lung interstitium and airspace is an early step in the host innate
      immune response to bacterial invasion of these sites. To determine the ability of
      intact bacteria to directly elicit PMN migration across an endothelial monolayer,
      we studied in vitro migration of PMNs across a monolayer of human pulmonary
      microvascular endothelial cells in response to Streptococcus pneumoniae,
      Staphylococcus aureus, and Escherichia coli, as well as to purified E. coli LPS.
      Bacterial induction of PMN migration was dose dependent and elicited by > or
      =10(4) bacteria/ml of each of the species tested. Pretreatment of PMNs with
      blocking Abs to CD18 significantly inhibited migration of PMN in response to all
      stimuli tested, but had the most profound effect on migration to S. pneumoniae
      and S. aureus. Intact E. coli were 10 times more potent in inducing
      transmigration of PMNs than a corresponding amount of purified LPS. Bacterial
      induction of PMN migration did not correlate with up-regulation of surface
      endothelial ICAM-1 expression (purified LPS >> intact E. coli > S. aureus and S.
      pneumoniae) nor up-regulation of VCAM-1 and E-selectin. Neutralizing Ab to ICAM-1
      had no effect on PMN migration to any of the bacteria or to purified LPS. These
      findings demonstrate that diverse bacterial pathogens induce PMN migration across
      a pulmonary microvascular endothelial cell monolayer in a fashion that appears to
      be organism specific. In addition, intact bacteria elicit PMN-endothelial cell
      interactions distinct from those seen when purified bacterial products are used
      as agonists.

PMID- 14688352
TI  - Critical role of T cell-dependent serum antibody, but not the gut-associated
      lymphoid tissue, for surviving acute mucosal infection with Citrobacter
      rodentium, an attaching and effacing pathogen.
AB  - Citrobacter rodentium uses virulence factors similar to the enteropathogenic
      Escherichia coli to produce attaching and effacing lesions in the distal colon of
      mice. We used this infection model to determine components of adaptive immunity
      needed to survive infection. During acute infection, wild-type mice develop
      breaks across infected epithelial surfaces but resolve infection. Surprisingly,
      mice markedly deficient in mucosal lymphocyte populations from beta(7) integrin
      deficiency resolve infection, as do CD8alpha-/- or TCR-delta-/- mice. In
      contrast, CD4-/- or TCR-beta-/- mice develop polymicrobial sepsis and end-organ
      damage, and succumb during acute infection, despite epithelial damage similar to
      wild-type mice. B cell-deficient (MuMT-/-) or B and T cell-deficient (recombinase
      activating gene 2-/-) mice develop severe pathology in colon and internal organs,
      and deteriorate rapidly during acute infection. Surviving mice develop robust
      Citrobacter-specific serum IgM responses during acute infection, whereas mice
      that succumb do not. However, CD4-/- mice receiving serum Igs from infected wild
      type mice survive and clear the infection. Our data show that survival of
      apparently self-limited and luminal mucosal infections requires a systemic T cell
      dependent Ab response against bacteria that enter through damaged mucosa. These
      findings have implications for understanding host defense against mucosal
      infections, including the pathogenesis of these diseases in immunocompromised
      populations.

PMID- 14688353
TI  - Redox-sensing release of human thioredoxin from T lymphocytes with negative
      feedback loops.
AB  - Thioredoxin (TRX) is released from various types of mammalian cells despite no
      typical secretory signal sequence. We show here that a redox-active site in TRX
      is essential for its release from T lymphocytes in response to H2O2 and
      extracellular TRX regulates its own H2O2-induced release. Human T cell leukemia
      virus type I-transformed T lymphocytes constitutively release a large amount of
      TRX. The level of TRX release is augmented upon the addition of H2O2, but
      suppressed upon the addition of N-acetylcysteine. In the culture supernatant of a
      Jurkat transfectant expressing the tagged TRX-wild type (WT), the tagged TRX
      protein is rapidly released at 1 h and kept at a constant level until 6 h after
      the addition of H2O2. In contrast, another type of transfectant expressing the
      tagged TRX mutant (C32S/C35S; CS) fails to release the protein. H2O2-induced
      release of TRX from the transfectant is inhibited by the presence of rTRX-WT in a
      dose-dependent manner. Preincubation of the transfectant with rTRX-WT for 1 h at
      37 degrees C, but not 0 degrees C, results in a significant suppression of the
      TRX release, reactive oxygen species, and caspase-3 activity induced by H2O2,
      respectively. Confocal microscopy and Western blot analysis show that
      extracellular rTRX-WT added to the culture does not obviously enter T lymphocytes
      until 24 h. These results collectively suggest that the oxidative stress-induced
      TRX release from T lymphocytes depends on a redox-sensitive event and may be
      regulated by negative feedback loops using reactive oxygen species-mediated
      signal transductions.

PMID- 14688354
TI  - Modulation of the phosphoinositide 3-kinase pathway alters innate resistance to
      polymicrobial sepsis.
AB  - We examined the effect of modulating phosphoinositide 3-kinase (PI3K) activity in
      a murine model of cecal ligation and puncture-induced polymicrobial sepsis.
      Inhibition of PI3K activity with wortmannin increased serum cytokine levels and
      decreased survival time in septic mice. We have reported that an immunomodulator,
      glucan phosphate, induces protection in murine polymicrobial sepsis. We observed
      that glucan stimulated tissue PI3K activity, which positively correlated with
      increased survival in septic mice. We investigated the effect of PI3K inhibition
      on survival in septic mice treated with glucan. Treatment of mice with the PI3K
      inhibitors, wortmannin and LY294002, completely eliminated the protective effect
      of glucan, indicating that protection against septic mortality was mediated
      through PI3K. Inhibition of PI3K resulted in increased serum levels of IL1-beta,
      IL-2, IL-6, IL-10, IL-12, and TNF-alpha in septic mice. Apoptosis is thought to
      play a central role in the response to septic injury. We observed that inhibition
      of PI3K activity in septic mice resulted in increased splenocyte apoptosis and a
      change in the anatomic distribution of splenocyte apoptosis. We conclude that
      PI3K is a compensatory mechanism that suppresses proinflammatory and apoptotic
      processes in response to sepsis and/or inflammatory injury. Thus, PI3K may play a
      pivotal role in the maintenance of homeostasis and the integrity of the immune
      response during sepsis. We also observed that glucan phosphate decreased septic
      morbidity and mortality through a PI3K-dependent mechanism. This suggests that
      stimulation of the PI3K pathway may be an effective approach for preventing or
      treating sepsis and/or septic shock.

PMID- 14688355
TI  - STAT1 plays a critical role in the regulation of antimicrobial effector
      mechanisms, but not in the development of Th1-type responses during
      toxoplasmosis.
AB  - The production of IFN-gamma by T cells and the ability of this cytokine to
      activate the transcription factor STAT1 are implicated in the activation of
      antimicrobial mechanisms required for resistance to intracellular pathogens. In
      addition, recent studies have suggested that the ability of STAT1 to inhibit the
      activation of STAT4 prevents the development of Th1 responses. However, other
      studies suggest that STAT1 is required to enhance the expression of T-bet, a
      transcription factor that promotes Th1 responses. To address the role of STAT1 in
      resistance to T. gondii, Stat1-/- mice were infected with this pathogen, and
      their response to infection was assessed. Although Stat1-/- mice produced normal
      serum levels of IL-12 and IFN-gamma, these mice were unable to control parasite
      replication and rapidly succumbed to this infection. Susceptibility to
      toxoplasmosis was associated with an inability to up-regulate MHC expression on
      macrophages, defects in NO production, and the inability to up-regulate some of
      the IFN-inducible GTPase family of proteins, molecules associated with
      antitoxoplasma activity. Analysis of T cell responses revealed that STAT1 was not
      required for the development of a Th1 response, but was required for the
      infection-induced up-regulation of T-bet. Together these studies suggest that
      during toxoplasmosis the major role of STAT1 is not in the development of
      protective T cell responses, but, rather, STAT1 is important in the development
      of antimicrobial effector mechanisms.

PMID- 14688356
TI  - Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic
      cells in cancer.
AB  - Abnormal differentiation of myeloid cells is one of the hallmarks of cancer.
      However, the molecular mechanisms of this process remain elusive. In this study,
      we investigated the effect of tumor-derived factors on Janus kinase (Jak)/STAT
      signaling in myeloid cells during their differentiation into dendritic cells.
      Tumor cell conditioned medium induced activation of Jak2 and STAT3, which was
      associated with an accumulation of immature myeloid cells. Jak2/STAT3 activity
      was localized primarily in these myeloid cells, which prevented the
      differentiation of immature myeloid cells into mature dendritic cells. This
      differentiation was restored after removal of tumor-derived factors. Inhibition
      of STAT3 abrogated the negative effects of these factors on myeloid cell
      differentiation, and overexpression of STAT3 reproduced the effects of tumor
      derived factors. Thus, this is a first demonstration that tumor-derived factors
      may affect myeloid cell differentiation in cancer via constitutive activation of
      Jak2/STAT3.

PMID- 14688357
TI  - Dendritic cells from malaria-infected mice are fully functional APC.
AB  - Malaria infection has long been associated with diminished T cell responses in
      vitro and more recently in experimental studies in vivo. Suppression of T cell
      proliferative responses during malaria has been attributed to macrophages in a
      variety of murine and human systems. More recently, however, attention has been
      directed at the role of dendritic cells in this phenomenon, with several studies
      suggesting that maturation of dendritic cells is inhibited in vitro by the
      presence of malaria-infected E. In the studies reported here, we have examined
      the function of dendritic cells taken directly from infected mice. We found that
      they express high levels of costimulatory proteins and class II MHC, can activate
      naive T cells to produce IL-2 as efficiently as dendritic cells from uninfected
      mice, and support high levels of IFN-gamma production by naive T cells through an
      IL-12-dependent mechanism. Dendritic cells from infected mice also support higher
      levels of TNF-alpha production by naive T cells. These same dendritic cells
      present parasite Ag to a malaria-specific T cell hybridoma, a finding that
      demonstrates that dendritic cells participate in the generation of Ag-specific
      immunity during infection. Our findings challenge the contention that dendritic
      cell function is inhibited by malaria infection.

PMID- 14688358
TI  - Conserved hierarchy of helper T cell responses in a chimpanzee during primary and
      secondary hepatitis C virus infections.
AB  - Control of hepatitis C virus (HCV) infection could be influenced by the timing
      and magnitude of CD4+ T cell responses against individual epitopes. We
      characterized CD4+ T cells targeting seven Pan troglodytes (Patr) class II
      restricted epitopes during primary and secondary HCV infections of a chimpanzee.
      All Patr-DR-restricted HCV epitopes bound multiple human HLA-DR molecules,
      indicating the potential for overlap in epitopes targeted by both species. Some
      human MHC class II molecules efficiently stimulated IL-2 production by chimpanzee
      virus-specific T cell clones. Moreover, one conserved epitope designated
      NS3(1248) (GYKVLVLNPSV) overlapped a helper epitope that is presented by multiple
      HLA-DR molecules in humans who spontaneously resolved HCV infection. Resolution
      of primary infection in the chimpanzee was associated with an initial wave of
      CD4+ T cells targeting a limited set of dominant epitopes including NS3(1248.) A
      second wave of low-frequency CD4+ T cells targeting other subdominant epitopes
      appeared in blood several weeks later after virus replication was mostly
      contained. During a second infection 7 years later, CD4+ T cells against all
      epitopes appeared in blood sooner and at higher frequencies but the pattern of
      dominance was conserved. In summary, primary HCV infection in this individual was
      characterized by T cell populations targeting two groups of MHC class II
      restricted epitopes that differed in frequency and kinetics of appearance in
      blood. The hierarchial nature of the CD4+ T cell response, if broadly applicable
      to other HCV-infected chimpanzees and humans, could be a factor governing the
      outcome of HCV infection.

PMID- 14688359
TI  - Galectin-3 mediates IL-4-induced survival and differentiation of B cells:
      functional cross-talk and implications during Trypanosoma cruzi infection.
AB  - The role of transcription factors in B cell survival and differentiation has been
      delineated during the last years. However, little is known about the intermediate
      signals and the intracellular pathways that control these events. In this study,
      we provide evidence both in vitro and in vivo, showing that galectin-3 (Gal-3), a
      beta-galactoside-binding protein, is a critical mediator of B cell
      differentiation and survival. Although Gal-3 is not expressed in resting B cells
      from normal mice, its expression is markedly induced after activation with
      stimuli such as IL-4 and CD40 cross-linking. These signals promote survival and
      block the final differentiation of these cells, thus allowing the rising of a
      memory B cell phenotype. In addition, Gal-3 is expressed in B cells from
      Trypanosoma cruzi-infected mice, which received signals for activation and
      differentiation in vivo. By using an antisense strategy, we determined that Gal-3
      is a critical signal mediating the effects of IL-4 on B cell fate. Blockade of
      intracellular Gal-3 in vitro abrogated IL-4-induced survival of activated B
      cells, favoring the differentiation toward a plasma cell pathway. Moreover, B
      cells with restrained endogenous Gal-3 expression failed to down-regulate the
      Blimp-1 transcription factor after IL-4 stimulation. Finally, inhibition of Gal-3
      in vivo skewed the balance toward plasma cell differentiation, which resulted in
      increased Ig production and parasite clearance during T. cruzi infection. Thus,
      the present study provides evidence of a novel role for Gal-3 as an intracellular
      mediator of B cell survival and a checkpoint in IL-4-induced B cell commitment
      toward a memory phenotype.

PMID- 14688360
TI  - Improved effector activity and memory CD8 T cell development by IL-2 expression
      during experimental respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) is a major cause of lower respiratory infection
      in young children and the elderly. Studies of mice suggest that RSV suppresses
      the effector activity of CD8 T cells and the development of pulmonary CD8 T cell
      memory, in which the impaired effector activity could be recovered by in vitro IL
      2 treatment. To investigate the effect of in vivo IL-2 expression on RSV
      immunity, mice were infected with RSV followed by administration of replication
      defective adenovirus expressing IL-2. The effector activity of RSV M2-specific
      CD8 T cells and the development of CD8 T cell memory in the lung was
      significantly increased by IL-2 expression. Furthermore, the Ab responses against
      RSV were augmented by IL-2. Interestingly, weight loss and illness caused by RSV
      challenge were substantially reduced by IL-2 priming, suggesting that the
      pathogenesis of RSV-related disease could be prevented by IL-2-mediated
      enhancement of beneficial immune responses. Thus, our results show that IL-2 has
      potential to be used as a vaccine adjuvant against RSV infection.

PMID- 14688361
TI  - Neutrophil serine proteinases cleave bacterial flagellin, abrogating its host
      response-inducing activity.
AB  - After bacterial infection, neutrophils dominate the cellular infiltrate. Their
      main function is assumed to be killing invading pathogens and resolving the
      inflammation they cause. Activated neutrophils are also known to release a
      variety of molecules, including the neutrophil serine proteinases,
      extracellularly. The release of these proteinases during inflammation creates a
      proteolytic environment where degradation of different molecules modulates the
      inflammatory response. Flagellin, the structural component of flagella on many
      bacterial species, is a virulence factor with a strong proinflammatory activity
      on epithelial cells and other cell types. In this study we show that both human
      and mouse neutrophil serine proteinases cleave flagellin from Pseudomonas
      aeruginosa and other bacterial species. More important, cleavage of P. aeruginosa
      flagellin by the neutrophil serine proteinases neutrophil elastase and cathepsin
      G resulted in loss of the biological activity of this virulence factor, as
      evidenced by the lack of innate host defense gene expression in human epithelial
      cells. The finding that flagellin is susceptible to cleavage by neutrophil serine
      proteinases suggests a novel role for these enzymes in the inflammatory response
      to infection. Not only can these enzymes kill bacteria, but they also degrade
      their virulence factors to halt the inflammatory response they trigger.

PMID- 14688362
TI  - Murine gamma-herpesvirus-68-induced IL-12 contributes to the control of latent
      viral burden, but also contributes to viral-mediated leukocytosis.
AB  - Early IFN-alpha/beta production, followed by the development of a viral-specific
      CTL response, are critical factors in limiting the level of murine gamma
      herpesvirus-68 (gammaHV-68) infection. Development of a long-lived CTL response
      requires T cell help, and these CTLs most likely function to limit the extent of
      infection following reactivation. The importance of IL-12 in the development
      and/or activity of Th1 cells and CTLs is well documented, and we investigated the
      kinetics and magnitude of gammaHV-68-induced IL-12 production. Following
      intranasal infection, IL-12 and IL-23 mRNA expression was up-regulated in lung
      and spleen and lung, respectively, followed by increased levels of IL-12p40 in
      lung homogenates and sera. Exposure of cultured macrophages or dendritic cells to
      gammaHV-68 induced secretion of IL-12, suggesting that these cells might be
      responsible for IL-12 production in vivo. gammaHV-68 infection of mice made
      genetically deficient in IL-12p40 expression (IL-12p40(-/-)) resulted in a
      leukocytosis and splenomegaly that was significantly less than that observed in
      syngeneic C57BL/6 mice. IL-12p40(-/-) mice showed increased levels of infectious
      virus in the lung, but only at day 9 postinfection. Increased levels of latent
      virus in the spleen at day 15 postinfection were also observed in IL-12p40(-/-)
      mice when compared with syngeneic C57BL/6 mice. An overall reduction in gammaHV
      68-induced IFN-gamma production was observed in IL-12p40(-/-) mice, suggesting
      that most of the viral-induced IFN-gamma in C57BL/6 mice was IL-12 dependent.
      Taken together, these results suggest that gammaHV-68-induced IL-12 contributes
      to the pathophysiology of viral infection while also functioning to limit viral
      burden.

PMID- 14688363
TI  - IL-23 induces stronger sustained CTL and Th1 immune responses than IL-12 in
      hepatitis C virus envelope protein 2 DNA immunization.
AB  - IL-23 is a heterodimeric cytokine consisting of p19 and the p40 subunit of IL-12.
      IL-23 has been shown to possess IL-12-like biological activities, but is
      different in its capacity to stimulate memory T cells in vitro. In this study, we
      investigated whether IL-23 could influence envelope protein 2 (E2)-specific cell
      mediated immunity induced by immunization of hepatitis C virus E2 DNA. We found
      that IL-23 induced long-lasting Th1 and CTL immune responses to E2, which are
      much stronger than IL-12-mediated immune responses. Interestingly, IL-23N220L, an
      N-glycosylation mutant showing reduced expression of excess p40 without changing
      the level of IL-23, exhibited a higher ratio of IFN-gamma- to IL-4-producing
      CD4(+) T cell frequency than did wild-type IL-23, suggesting a negative
      regulatory effect of p40 on Th1-prone immune response induced by IL-23. These
      data suggest that IL-23, particularly IL-23N220L, would be an effective adjuvant
      of DNA vaccine for the induction of durable Ag-specific T cell immunity.

PMID- 14688364
TI  - Differential regulation of IgG anti-capsular polysaccharide and antiprotein
      responses to intact Streptococcus pneumoniae in the presence of cognate CD4+ T
      cell help.
AB  - The relative lack of memory for IgG antipolysaccharide responses is believed to
      be secondary to the inability of polysaccharides to associate with MHC class II
      molecules and thus a failure to recruit cognate CD4+ T cell help. However, little
      is known concerning the role of T cells and the generation of memory for
      antipolysaccharide Ig responses to intact extracellular bacteria. We used heat
      killed, intact Streptococcus pneumoniae, capsular type 14 (Pn14), to evaluate the
      IgM and IgG responses specific for the capsular polysaccharide (PPS14), the
      phosphorylcholine determinant of the cell wall C-polysaccharide, and the cell
      wall protein, pneumococcal surface protein A (PspA). We demonstrate that the IgG
      (but not IgM), anti-PPS14, and anti-PspA responses to Pn14 are CD4+ T cell
      dependent and TCR specific. Nevertheless, in contrast to the anti-PspA response,
      the IgG anti-PPS14 response shows no apparent memory, an accelerated kinetics of
      primary Ig induction, and a more rapid delivery of CD4+ T cell help. In contrast,
      the IgG anti-phosphorylcholine response, although also dependent on CD4+ T cells,
      is TCR nonspecific. We make similar observations using soluble conjugates of
      PPS14-PspA and C-polysaccharide-PspA. These data lead us to suggest that the
      central issue concerning the mechanisms underlying different functional outcomes
      for anti-bacterial IgG responses to capsular polysaccharide vs protein Ags is not
      necessarily based on the ability to recruit cognate CD4+ T cell help, but perhaps
      on the nature of the B cell Ag receptor signaling that occurs and/or on the
      responding B cell subpopulations.

PMID- 14688365
TI  - Proteolytic regulation of the urokinase receptor/CD87 on monocytic cells by
      neutrophil elastase and cathepsin G.
AB  - The urokinase receptor (CD87) participates to the pericellular proteolytic
      potential of migrating cells and to the recruitment of leukocytes during
      inflammation. It consists of three structurally homologous domains, with the C
      terminal domain D3 attached to cell membranes through a GPI anchor. CD87 is
      susceptible to an endoproteolytic processing removing the N-terminal domain D1
      and generating truncated D2D3 membrane species, thus modulating CD87-associated
      functions. Full-length or truncated CD87 can be also released from cells via
      juxtamembrane cleavage by phospholipases and/or by yet unidentified proteinases.
      Using a recombinant CD87 and the CD87-positive monocytic U937 cell line and
      isolated blood monocytes, we show by protein immunoblotting and flow
      immunocytometry that the human neutrophil serine-proteinases elastase and
      cathepsin G cleave CD87 within the D1-D2 linker sequence, while in addition
      cathepsin G is highly efficient in cleaving the C terminus of D3. The combination
      of cathepsin G and elastase provided by degranulated neutrophils results in
      enzymatic cooperation leading to the release from monocytic cells of a truncated
      D2D3 species resembling that previously described in pathological body fluids.
      Using mass spectrometry analysis, the proteolytic fragmentation of synthetic
      peptides mapping the D1-D2 linker and D3 C-terminal domains identifies potential
      cleavage sites for each enzyme and suggests the existence of a mechanism
      regulating the CD87(D1-D2)-associated chemotactic activity. Finally, isolated or
      combined elastase and cathepsin G drastically reduce the capacity of cells to
      bind urokinase. Secretable leukocyte serine-proteinases are thus endowed with
      high potential for the regulation of CD87 expression and function on inflammatory
      cells.

PMID- 14688366
TI  - IFN-inducible protein 10/CXC chemokine ligand 10-independent induction of
      experimental autoimmune encephalomyelitis.
AB  - In multiple sclerosis (MS) and its animal model, experimental autoimmune
      encephalomyelitis (EAE), autoaggressive T cells traffic into the CNS and induce
      disease. Infiltration of these pathogenic T cells into the CNS has been
      correlated with the expression of the chemokine IFN-inducible protein (IP)10/CXC
      chemokine ligand (CXCL)10, a chemoattractant for activated T cells, and its
      receptor CXCR3, in the CNS of both MS patients and mice with EAE. In the present
      study, we report that targeted deletion of IP-10 did not diminish the expression,
      severity, or histopathology of EAE induced by active immunization with 100 micro
      g of myelin oligodendrocyte glycoprotein peptide (MOG)p35-55. However, we found
      that IP-10-deficient mice had a lower threshold for expression of disease
      compared with wild-type littermates. EAE induced by immunization with 5 micro g
      of MOGp35-55 resulted in more severe disease characterized by a greater number of
      CNS lesions and infiltrating mononuclear cells in IP-10-deficient mice compared
      with wild-type controls. IP-10-deficient mice immunized with MOGp35-55
      demonstrated increased levels of IFN-inducible T cell alpha-chemokine/CXCL11 mRNA
      in the CNS and decreased levels of monokine induced by IFN-gamma/CXCL9 mRNA in
      draining lymph nodes, suggesting differential compensation for loss of IP-10 in
      lymphoid vs parenchymal tissue compartments. EAE in IP-10-deficient mice induced
      by low-dose immunization was associated with enhanced Ag-specific Th1 responses
      in the draining lymph node, which corresponded with diminished lymph node TGF
      beta1 expression. Our data demonstrated that IP-10 was not required for the
      trafficking of pathogenic T cells into the CNS in EAE but played an unexpected
      role in determining the threshold of disease susceptibility in the periphery.

PMID- 14688367
TI  - Intracellular regulation of Fas-induced apoptosis in human fibroblasts by
      extracellular factors and cycloheximide.
AB  - Fibroblasts play an important role in reparative and inflammatory processes by
      synthesizing extracellular matrix components and releasing growth factors and
      cytokines. Fibroblast apoptosis has been observed at the termination phase of
      reparative or fibrotic responses, but its regulation in this context is poorly
      known. We investigated the susceptibility of human dermal fibroblasts (DF) to Fas
      induced apoptosis and its regulation by extracellular factors potentially
      involved in immune-mediated inflammation and repair. DF expressed all components
      of the Fas apoptotic pathway: surface Fas, Fas-associated protein with death
      domain, and caspase-8 proteins. However, Fas activation resulted in caspase-8
      activation and apoptosis only in the presence of cycloheximide (CHX). DF
      constitutively expressed Fas-associated death domain-like IL-1-converting enzyme
      like inhibitory protein (FLIP) that was drastically down-regulated by CHX.
      Exogenous growth factors, cytokines, and adherence to the extracellular matrix
      shifted the balance of FLIP-caspase-8 proteins and modified the susceptibility of
      DF to Fas- or Fas-CHX-induced apoptosis. Short-term serum deprivation, suspension
      culture, and pretreatment with IFN-gamma or TNF-alpha increased, whereas long
      term serum-free culture and pretreatment with TGF-beta or IL-10 decreased the
      apoptotic susceptibility of DF. Surface Fas expression was only modified by TNF
      alpha and IFN-gamma, whereas all studied factors modified FLIP-caspase-8 protein
      expression, consistently with their pro- or antiapoptotic effects. Antisense FLIP
      oligonucleotides prevented resistance to Fas-induced apoptosis in DF. FLIP
      caspase-8 balance seems tightly regulated in fibroblasts by extracellular factors
      that determine their susceptibility to Fas- or Fas-CHX-induced apoptosis. Th1 and
      Th regulatory cytokines display opposite effects on fibroblast apoptosis that
      suggest that their pro- or antifibrotic effects involve direct effects on
      fibroblast survival.

PMID- 14688368
TI  - Signal transducer and activator of transcription 3 is the dominant mediator of
      the anti-inflammatory effects of IL-10 in human macrophages.
AB  - The signaling mechanism by which the anti-inflammatory cytokine IL-10 mediates
      suppression of proinflammatory cytokine synthesis remains largely unknown.
      Macrophage-specific STAT3-null mice have demonstrated that STAT3 plays a critical
      role in the suppression of LPS-induced TNF-alpha release, although the mechanism
      by which STAT3 mediates this inhibition is still not clear. Using an adenoviral
      system, we have expressed a dominant negative (DN) STAT3 in human macrophages to
      broaden the investigation to determine the role of STAT3 in IL-10-mediated anti
      inflammatory signaling and gene expression. Overexpression of STAT3 DN completely
      inhibited IL-10-induced suppressor of cytokine signaling 3, tissue inhibitor of
      MMP-1, TNF receptor expression, and the recently identified IL-10-inducible
      genes, T cell protein tyrosine phosphatase and signaling lymphocyte activation
      molecule. STAT3 DN also blocked IL-10-mediated inhibition of MHC class II and
      COX2 expression. In agreement with the studies in STAT3-null mice, overexpression
      of the STAT3 DN completely reversed the ability of IL-10 to inhibit LPS-mediated
      TNF-alpha and IL-6 production. However, real-time PCR analysis showed that STAT3
      DN expression did not affect immediate suppression of TNF-alpha mRNA, but did
      reverse the suppression observed at later time points, suggesting a biphasic
      regulation of TNF-alpha mRNA levels by IL-10. In conclusion, although STAT3 does
      appear to be the dominant mediator of the majority of IL-10 functions, there are
      elements of its anti-inflammatory activity that are STAT3 independent.

PMID- 14688369
TI  - Membrane-associated IL-1 contributes to chronic synovitis and cartilage
      destruction in human IL-1 alpha transgenic mice.
AB  - IL-1 molecules are encoded by two distinct genes, IL-1alpha and IL-1beta. Both
      isoforms possess essentially identical activities and potencies, whereas IL
      1alpha, in contrast to IL-1beta, is known to act as a membrane-associated IL-1
      (MA-IL-1) and plays an important role in a variety of inflammatory situations.
      The transgenic (Tg) mouse line (Tg1706), which was generated in our laboratory,
      overexpresses human IL-1alpha (hIL-1alpha) and exhibits a severe arthritic
      phenotype characterized by autonomous synovial proliferation with subsequent
      cartilage destruction. Because the transgene encoded Lys(64) to Ala(271) of the
      hIL-1alpha amino acid sequence, Tg mice may overproduce MA-IL-1 as well as
      soluble IL-1alpha. The present study investigated whether MA-IL-1 contributes to
      synovial proliferation and cartilage destruction in the development of arthritis.
      Flow cytometric analysis revealed that both macrophage-like and fibroblast-like
      synoviocytes constitutively produce MA-IL-1. D10 cell proliferation assay
      revealed MA-IL-1 bioactivity of paraformaldehyde-fixed synoviocytes and the
      further induction of endogenous mouse MA-IL-1 via autocrine mechanisms. MA-IL-1
      expressed on synoviocytes triggered synoviocyte self-proliferation through cell
      to-cell (i.e., juxtacrine) interactions and also promoted proteoglycan release
      from the cartilage matrix in chondrocyte monolayer culture. Interestingly, the
      severity of arthritis was significantly correlated with MA-IL-1 activity rather
      than with soluble IL-1alpha activity or concentration of serum hIL-1alpha.
      Moreover, when the Tg1706 line was compared with the Tg101 line, which
      selectively overexpresses the 17-kDa mature hIL-1alpha, the severity of arthritis
      was significantly higher in the Tg1706 line than in the Tg101 line. These results
      suggest that MA-IL-1 contributes to synoviocyte self-proliferation and subsequent
      cartilage destruction in inflammatory joint disease such as rheumatoid arthritis.

PMID- 14688370
TI  - Soluble fractalkine prevents monocyte chemoattractant protein-1-induced monocyte
      migration via inhibition of stress-activated protein kinase 2/p38 and matrix
      metalloproteinase activities.
AB  - In this study, we address the question of the cross-talk between two chemokines
      that are cosecreted during inflammation, namely monocyte chemoattractant protein
      1 (MCP-1) and soluble fractalkine (s-FKN), toward monocyte migration. We found
      that s-FKN fails to induce MonoMac6 cell migration per se. Interestingly, this
      chemokine antagonizes transendothelial migration and chemotaxis of MonoMac6 cells
      and freshly isolated human monocytes induced by MCP-1, indicating a direct effect
      of s-FKN on monocytic cells. In this study, we found that stress-activated
      protein kinase (SAPK)1/c-Jun N-terminal kinase 1 and SAPK2/p38 are involved in
      the control of MCP-1-induced MonoMac6 cell migration. We demonstrated that s-FKN
      abrogates the MCP-1-induced SAPK2/p38 activation as well as the upstream Pyk2
      activity. Furthermore, we observed that s-FKN also inhibits the activity of a
      major matrix metalloproteinase (MMP), namely MMP-2. Taken collectively, our
      results indicate that the s-FKN antagonizes the chemoattractant effect of MCP-1
      on monocytes, likely by inhibiting crucial signaling pathways, like SAPK2/p38 and
      MMP-2 activities.

PMID- 14688371
TI  - Neutralizing endogenous IL-6 renders mast cells of the MCT type from lung, but
      not the MCTC type from skin and lung, susceptible to human recombinant IL-4
      induced apoptosis.
AB  - Human cord blood-derived mast cells undergo apoptosis upon exposure to
      recombinant human (rh)IL-4 and become resistant to rhIL-4-induced apoptosis when
      cultured in the presence of rhIL-6. The current study extends these effects of
      rhIL-4 to different populations of human mast cells, namely fetal liver-derived
      mast cells, lung-derived mast cells, and skin-derived mast cells. Endogenous
      production of IL-6 appears to protect fetal liver-derived mast cells and those of
      the MC(T) phenotype from rhIL-4-mediated apoptosis, because neutralization of IL
      6 renders these mast cells sensitive. In contrast, mast cells of the MC(TC)
      phenotype from skin and lung were resistant to IL-4-mediated apoptosis, even
      after neutralization of endogenous IL-6. MC(TC) cells were CD124(low), whereas
      those of the MC(T) cells were CD124(high). These observations extend the
      phenotypic differences between MC(T) and MC(TC) types of human mast cells to
      include different functional responses to IL-4.

PMID- 14688372
TI  - Cytoskeletal reorganization internalizes multiple transient receptor potential
      channels and blocks calcium entry into human neutrophils.
AB  - Store-operated calcium entry (SOCE) is required for polymorphonuclear neutrophil
      (PMN) activation in response to G protein-coupled agonists. Some immunocytes
      express proteins homologous to the Drosophila transient receptor potential gene
      (trp) calcium channel. TRP proteins assemble into heterotetrameric ion channels
      and are known to support SOCE in overexpression systems, but the evidence that
      TRP proteins support SOCE and are functionally important in wild-type cells
      remains indirect. We therefore studied the expression and function of TRP
      proteins in primary human PMN. TRPC1, TRPC3, TRPC4, and TRPC6 were all expressed
      as mRNA as well as membrane proteins. Immunofluorescence microscopy demonstrated
      localization of TRPC1, TRPC3, and TRPC4 to the PMN cell membrane and their
      internalization after cytoskeletal reorganization by calyculin A (CalyA). Either
      TRPC internalization by CalyA or treatment with the inositol triphosphate
      receptor inhibitor 2-aminoethoxydiphenyl borane resulted in the loss of PMN SOCE.
      Cytochalasin D (CytoD) disrupts actin filaments, thus preventing cytoskeletal
      reorganization, and pretreatment with CytoD rescued PMN SOCE from inhibition by
      CalyA. Comparative studies of CytoD and 2-aminoethoxydiphenyl borane inhibition
      of PMN cationic entry after thapsigargin or platelet-activating factor suggested
      that SOCE occurs through both calcium-specific and nonspecific pathways. Taken
      together, these studies suggest that the multiple TRPC proteins expressed by
      human PMN participate in the formation of at least two store-operated calcium
      channels that have differing ionic permeabilities and regulatory characteristics.

PMID- 14688373
TI  - Intercellular adhesion molecule-1 mediates cellular cross-talk between
      parenchymal and immune cells after lipopolysaccharide neutralization.
AB  - The mechanisms by which parenchymal cells interact with immune cells,
      particularly after removal of LPS, remain unknown. Lung explants from rats, mice
      deficient in the TNF gene, or human lung epithelial A549 cells were treated with
      LPS and washed, before naive alveolar macrophages, bone marrow monocytes, or
      PBMC, respectively, were added to the cultures. When the immune cells were
      cocultured with LPS-challenged explants or A549 cells, TNF production was greatly
      enhanced. This was not affected by neutralization of LPS with polymyxin B. The
      LPS-induced increase in the expression of ICAM-1 on A549 cells correlated with
      TNF production by PBMC. The cellular cross talk leading to the TNF response was
      blunted by an anti-ICAM-1 Ab and an ICAM-1 antisense oligonucleotide. In A549
      cells, a persistent decrease in the concentration of intracellular cAMP was
      associated with colocalization of LPS into Toll-like receptor 4 and the Golgi
      apparatus, resulting in increased ICAM-1 expression. Inhibition of LPS
      internalization by cytochalasin D or treatment with dibutyryl cAMP attenuated
      ICAM-1 expression and TNF production by PBMC. In conclusion, lung epithelial
      cells are not bystanders, but possess memory of LPS through the expression of
      ICAM-1 that interacts with and activates leukocytes. This may provide an
      explanation for the failure of anti-LPS therapies in sepsis trials.

PMID- 14688374
TI  - Corticosteroids regulate epithelial cell differentiation and Hassall body
      formation in the human thymus.
AB  - The presence of characteristic epithelial swirls called Hassall bodies within the
      human thymic medulla has been used as an indicator of ongoing or recent
      thymopoiesis. We present a case where Hassall bodies were present in the absence
      of current or past thymopoiesis. The patient had been treated with
      corticosteroids for presumed asthma before his diagnosis of X-linked SCID. Two
      other cases of nonimmunodeficient patients treated with high-dose corticosteroids
      had markedly increased numbers of thymic Hassall bodies. To determine whether
      corticosteroid treatment induces thymic epithelial (TE) differentiation to form
      Hassall bodies, mAbs reactive with specific cytokeratins (CKs), filaggrin, and
      involucrin were used to define distinct stages of TE cell differentiation.
      Treatment of primary TE monolayers with hydrocortisone in vitro induced
      expression of involucrin and high-molecular-mass CKs that are characteristic of
      TE differentiation. Treatment of thymic organ cultures with hydrocortisone
      induced both medullary and subcapsular cortical TE cells to express CK6, a
      differentiation marker that is normally expressed only by Hassall bodies in vivo.
      These experimental studies combined with the case observations indicate that
      exogenous corticosteroids can regulate terminal differentiation of TE cells both
      in vitro and in vivo. Thus, the presence of Hassall bodies in thymus from
      corticosteroid-treated patients cannot be taken as an absolute indication of
      previous thymopoiesis. Because corticosteroids are also made within the thymus
      under normal physiologic conditions, these studies support the hypothesis that
      endogenous corticosteroids may play a role in normal TE differentiation and
      Hassall body formation in vivo.

PMID- 14688375
TI  - Impaired clearance of apoptotic cells induces the activation of autoreactive anti
      Sm marginal zone and B-1 B cells.
AB  - Since apoptotic cell Ags are thought to be a source of self-Ag in systemic lupus
      erythematosus, we have examined the role of apoptotic cells in the regulation and
      activation of B cells specific for Sm, a ribonucleoprotein targeted in human and
      murine lupus. Using Ig-transgenic mice that have a high frequency of anti-Sm B
      cells, we find that apoptotic cell injection induces a transient splenic B cell
      response, while simultaneously causing extensive splenic and peritoneal anti-Sm B
      cell death. In contrast, mice deficient in the clearance of apoptotic cells
      develop a chronic anti-Sm response beginning at 1-2 mo of age. These mice have
      expanded marginal zone and B-1 B cell populations and anti-Sm B cells of both
      types are activated to form Ab-secreting cells. This activation appears to be Ag
      specific, suggesting that activation is due to increased availability of
      apoptotic cell Ags. Since marginal zone and B-1 cells are positively selected,
      these data suggest a loss of ignorance rather than a loss of tolerance.

PMID- 14688376
TI  - Gene expression profiling provides insight into the pathophysiology of chronic
      granulomatous disease.
AB  - Human polymorphonuclear leukocytes (PMNs or neutrophils) kill invading
      microorganisms with reactive oxygen species (ROS) and cytotoxic granule
      components. PMNs from individuals with X-linked chronic granulomatous disease
      (XCGD) do not produce ROS, thereby rendering these individuals more susceptible
      to infection. In addition, XCGD patients develop tissue granulomas that obstruct
      vital organs, the mechanism(s) for which are unknown. To gain insight into the
      molecular processes that contribute to the pathophysiology of XCGD, including
      formation of granulomas, we compared global gene expression in PMNs from XCGD
      patients and healthy control individuals. Genes encoding mediators of
      inflammation and host defense, including CD11c, CD14, CD54, FcgammaR1, FcalphaR,
      CD120b, TLR5, IL-4R, CCR1, p47(phox), p40(phox), IL-8, CXCL1, Nramp1, and
      calgranulins A and B, were up-regulated constitutively in unstimulated XCGD
      patient PMNs. By comparing transcript levels in normal and XCGD PMNs after
      phagocytosis, we discovered 206 genes whose expression changed in the presence
      and the absence of ROS, respectively. Notably, altered Bcl2-associated X protein
      synthesis accompanied defective neutrophil apoptosis in XCGD patients. We
      hypothesize that granuloma formation in XCGD patients reflects both increased
      proinflammatory activity and defective PMN apoptosis, and we conclude that ROS
      contribute directly or indirectly to the resolution of the inflammatory response
      by influencing PMN gene transcription.

PMID- 14688377
TI  - Determinants of antileukemia effects of allogeneic NK cells.
AB  - In HLA-nonidentical bone marrow transplantation, we studied the characteristics
      of donor NK cells, recipient leukemia cells, and the cytokine environment that
      predict the antileukemia effects of allogeneic NK cells. We found that the risk
      of relapse in pediatric patients with hematologic malignancies was best predicted
      by a model taking into consideration the presence of inhibitory killer cell Ig
      like receptors (KIRs) on the donor's NK cells and the absence of corresponding
      KIR ligand in the recipient's HLA repertoire (a receptor-ligand model). The risk
      of relapse was prognosticated less precisely by the Perugia donor-recipient KIR
      ligand-ligand mismatch model or by a natural cytotoxicity model. In contrast to
      the ligand-ligand model, we found that the new receptor-ligand model was accurate
      when analysis was applied to patients with lymphoid malignancy. These findings
      corroborate our observations that the recipient's KIR repertoire, which was
      derived from highly purified, HLA-disparate CD34+ cells, resumed a donor-specific
      pattern within 3 mo of transplantation, but did not correlate evidently with the
      donor or recipient ligand repertoire. In an in vitro assay and an in vivo mouse
      model, human NK cell cytotoxicity toward human leukemia cells with 11q23
      chromosomal rearrangement increased with the number of receptor-ligand mismatch
      pairs or prestimulation with IL-12 and IL-18. These findings provide new insights
      into the determinants of antileukemia effects of allogeneic NK cells and
      therapeutic strategies.

PMID- 14688378
TI  - A novel mechanism of alternative promoter and splicing regulates the epitope
      generation of tumor antigen CML66-L.
AB  - This report describes the difference in the epitope generation of two isoforms of
      self-tumor Ag CML66 and the regulation mechanism. We identified a new CML66 short
      isoform, termed CML66-S. The previously identified long CML66 is referred to as
      CML66-L. CML66-S shares the C terminus with CML66-L but has its unique N
      terminus. CML66-S is predominantly expressed in testis, but is also expressed in
      very low levels in tumor cells, whereas CML66-L is expressed in tumor cells and
      testis. Differential expression of CML66-L and CML66-S in tumor cells resulted
      from regulation at transcription, although alternative splicing also participated
      in the generation of the isoforms. In addition, Ab titers to a CML66-L peptide
      were significantly higher than that to CML66-S peptide in the sera from patients
      with tumors. Finally, the Abs to full-length CML66-L in the sera from patients
      with tumors were correlated with the Abs in the sera from these patients to CML66
      L-38, which is a fusion protein with a CML66-L-specific N terminus. This suggests
      that the CML66-L isoform is mainly responsible for the epitope generation. Our
      studies have identified the alternative promoter in combination with alternative
      splicing as a novel mechanism for regulation of the epitope generation of a self
      tumor Ag.

PMID- 14688379
TI  - Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the
      milk protein butyrophilin in multiple sclerosis.
AB  - The etiology of multiple sclerosis (MS) is believed to involve environmental
      factors, but their identity and mode of action are unknown. In this study, we
      demonstrate that Ab specific for the extracellular Ig-like domain of myelin
      oligodendrocyte glycoprotein (MOG) cross-reacts with a homologous N-terminal
      domain of the bovine milk protein butyrophilin (BTN). Analysis of paired samples
      of MS sera and cerebrospinal fluid (CSF) identified a BTN-specific Ab response in
      the CNS that differed in its epitope specificity from that in the periphery. This
      effect was statistically significant for the Ab response to BTN(76-100) (p =
      0.0026), which cosequestered in the CSF compartment with Ab to the homologous MOG
      peptide MOG(76-100) in 34% of MS patients (n = 35). These observations suggested
      that intratheccal synthesis of Ab recognizing BTN peptide epitopes in the CNS was
      sustained by molecular mimicry with MOG. Formal evidence of molecular mimicry
      between the two proteins was obtained by analyzing MOG-specific autoantibodies
      immunopurified from MS sera. The MOG-specific Ab repertoire cross-reacts with
      multiple BTN peptide epitopes including a MOG/BTN(76-100)-specific component that
      occurred at a higher frequency in MS patients than in seropositive healthy
      controls, as well as responses to epitopes within MOG/BTN(1-39) that occur at
      similar frequencies in both groups. The demonstration of molecular mimicry
      between MOG and BTN, along with sequestration of BTN-reactive Ab in CSF suggests
      that exposure to this common dietary Ag may influence the composition and
      function of the MOG-specific autoimmune repertoire during the course of MS.

PMID- 14688380
TI  - Distortion of the self-reactive IgG antibody repertoire in multiple sclerosis as
      a new diagnostic tool.
AB  - To date, none of the myelin-associated Ag targets definitively discriminates
      between the immune response observed in multiple sclerosis (MS) patients and
      healthy subjects. However, it has been shown recently that analysis of global
      immune Ab profiles such as natural autoantibody reactivities can help to
      distinguish between normal individuals and patients suffering from various immune
      diseases. The aim of our study was to compare the global IgG immune response
      against brain self-Ags in sera from 82 MS patients and 27 healthy subjects. The
      analysis of the immune profiles was performed by Western blotting, and data were
      subjected to linear discriminant analysis. Particular patterns of IgG reactivity
      were found in healthy subjects, Sjogren patients, and MS patients. Moreover, this
      approach separated the three clinical forms of MS with a high concordance rate
      with the clinical data (kappa value, 77.8%). Our study suggests, for the first
      time, that serum IgG Ab repertoires are able to distinguish MS patients. In
      addition, our data suggest that patterns of IgG reactivity could model the
      pathological processes underlying the various forms of MS. Further
      characterization of such discriminant Ags could provide useful information
      regarding their potent role in pathogenesis or regulatory processes in MS.

PMID- 14688381
TI  - CD4+ T cells mediate murine syngeneic graft-versus-host disease-associated
      colitis.
AB  - Syngeneic graft-vs-host disease (SGVHD) develops following lethal irradiation,
      reconstitution with syngeneic bone marrow, and treatment with a 21-day course of
      the immunosuppressive agent cyclosporin A (CsA). Following cessation of CsA, this
      inducible disease is characterized by weight loss, diarrhea, and development of
      inflammation in the colon and liver. Although nonspecific effector cells and Th1
      cytokines have been shown to participate in disease induction, the role of T
      cells has not been fully elucidated. Initial studies demonstrated significant
      increases in CD4+ T cells, but not other T cell populations in the colons of
      diseased animals relative to transplant control animals. To demonstrate a
      functional linkage between increases in colonic CD4+ T cells and disease
      induction, in vivo T cell depletion studies were performed. Beginning on the day
      of bone marrow transplantation, groups of control and CsA-treated animals were
      treated with mAb against either CD4 or CD8 for 21 days. Treatment with anti-CD4,
      but not anti-CD8, eliminated clinical symptoms and colon pathology.
      Interestingly, neither anti-CD4 nor anti-CD8 therapy affected the development of
      liver pathology associated with SGVHD. These findings demonstrated that CD4+ T
      cells initiate development of the intestinal inflammation associated with murine
      SGVHD.

PMID- 14688382
TI  - NF-kappa B p65 antagonizes IL-4 induction by c-maf in minimal change nephrotic
      syndrome.
AB  - Mechanisms underlying the pathophysiology of minimal change nephrotic syndrome
      (MCNS), the most frequent of glomerular diseases in children, remain elusive,
      although recent arguments suggest that T cell dysfunction may be involved in the
      pathogenesis of this disease. Recently, we reported that activated T cells of
      these patients display a down-regulation of IL-12R beta2 chain, suggesting an
      early commitment toward Th2 phenotype. In this study, we show that the short form
      of the proto-oncogene c-maf, a known activator of the IL-4 gene, is highly
      induced in MCNS T cells during relapse, where it translocates to the nuclear
      compartment and binds to the DNA responsive element. Unexpectedly, the nuclear
      localization of c-maf did not promote the IL-4 gene transcription in relapse.
      Using several approaches, we show in this study that RelA blunts IL-4 induction
      in T cells during the relapse in these patients. We demonstrate that the ex vivo
      inhibition of proteasome activity in T cells from relapse, which blocks NF-kappaB
      activity, strongly increases the IL-4 mRNA levels. Overexpression of c-maf in T
      cells induces a high level of IL-4 promoter-driven luciferase activity. In
      contrast, coexpression of c-maf with NF-kappaB RelA/p50, or RelA, but not p50,
      inhibits the c-maf-dependent IL-4 promoter activity. Finally, we demonstrated
      that, in T cell overexpressing RelA and c-maf, RelA expelled c-maf from its DNA
      binding site on IL-4 gene promoter, which results in active inhibition of IL-4
      gene transcription. Altogether, these results suggest that the involvement of c
      maf in Th2 commitment in MCNS operates through IL-4-independent mechanisms.

PMID- 14688384
TI  - A major B cell epitope present on the apoptotic but not the intact form of the U1
      70-kDa ribonucleoprotein autoantigen.
AB  - Apoptotically modified forms of autoantigens have been hypothesized to
      participate in lupus immunopathogenesis. This study identifies a major B cell
      epitope present on the apoptotic but not the intact form of the U1-70-kDa
      ribonucleoprotein lupus autoantigen (70k). Human autoimmune sera with strong
      recognition of apoptotic 70k and minimal recognition of intact 70k were
      identified and tested for reactivity to truncated forms of 70k by immunoblot and
      ELISA. Patient sera that preferentially recognized apoptotic 70k were specific
      for an epitope dependent on residues 180-205 of the protein. This epitope was
      also recognized by 19 of 28 (68%) intact anti-70k-positive autoimmune human sera
      with Abs also recognizing apoptotic but not the intact form 70k, but only 1 of 9
      (11%) intact 70k-positive sera without such Abs (Fisher's exact, p = 0.0055).
      Immunization of HLA-DR4-transgenic C57BL/6 mice with a peptide containing this
      epitope induced anti-70k immunity in 13 of 15 mice, including Abs recognizing
      apoptotic but not intact forms of autoantigens in 12 of 15 mice. Anti-70k
      responder mice also developed spreading of immunity to epitopes on the endogenous
      form of 70k, and proliferative lung lesions consistent with those described in
      patients with anti-70k autoimmunity. Thus, a major epitope in the B cell response
      to U1-70 kDa localizes to the RNA binding domain of the molecule, overlaps with
      the most common T cell epitope in the anti-70k response, and is not present on
      the intact form of the 70k molecule. Immunization of mice against this epitope
      induces an immune response with features seen in human anti-70k autoimmune
      disease.

PMID- 14688383
TI  - Thymic selection and peripheral activation of CD8 T cells by the same class I
      MHC/peptide complex.
AB  - Thymic selection is controlled by the interaction between TCR and MHC/peptide.
      Strength and quality of the signal determine whether thymocytes are selected or
      deleted. The factors that contribute to this signal remain poorly defined. Here
      we show that fetal thymic organ cultures (FTOCs) derived from OT-I transgenic
      mice (the OT-I TCR is restricted by K(b)-SIINFEKL) on a K(b)D(b-/-) background
      support positive selection, but only when provided with soluble H-2K(b)-SIINFEKL
      complexes. Selection of CD8 T cells is independent of the valency of the ligand
      or its capability to coengage CD8 molecules. Both CD8alphaalpha and CD8alphabeta
      T cells are selected by H-2K(b)-SIINFEKL, but only CD8alphabeta cells are capable
      of releasing IFN-gamma in response to the same ligand. The alpha(4)beta(7)
      integrin is up-regulated on postselection thymocytes from FTOCs. After adoptive
      transfer, FTOC-derived OT-I CD8 T cells divide in response to the agonist peptide
      SIINFEKL. These results establish that CD8 T cells responsive to their nominal
      peptide-Ag can be generated in FTOC supplemented with soluble MHC class I
      molecules equipped with the same peptide.

PMID- 14688386
TI  - Enhancing and diminishing gene function in human embryonic stem cells.
AB  - It is widely recognized that gain- and loss-of-function approaches are essential
      for understanding the functions of specific genes, and such approaches would be
      particularly valuable in studies involving human embryonic stem (hES) cells. We
      describe a simple and efficient approach using lipofection to transfect hES
      cells, which enabled us to generate hES cell lines expressing naturally
      fluorescent green or red proteins without affecting cell pluripotency. We used
      these cell lines to establish a means of diminishing gene function using small
      interfering (si)RNAs, which were effective at knocking down gene expression in
      hES cells. We then demonstrated that stable expression of siRNA could knock down
      the expression of endogenous genes. Application of these gain- and loss-of
      function approaches should have widespread use, not only in revealing the
      developmental roles of specific human genes, but also for their utility in
      modulating differentiation.

PMID- 14688387
TI  - Limited contribution of circulating cells to the development and maintenance of
      nonhematopoietic bovine tissues.
AB  - Bone marrow-derived stem cells appear surprisingly multipotent in experimental
      settings, but the physiological significance of such plasticity is unclear. We
      have used sex-mismatched cattle twins with stably chimeric hematopoietic systems
      to investigate the general extent of integration of circulating cells to the
      nonhematopoietic cell lineages in an unmanipulated large mammal. The donor
      derived (Y+) nonhematopoietic cells in female recipient tissues were visualized
      by Y-chromosome specific in situ hybridization combined with pan-leukocyte
      labeling. Y+ leukocytes were frequent in all tissues, but in 11 of 12 animals,
      average contribution to nonhematopoietic lineages was in any tissue below 1% (in
      brain <0.001%). Significantly higher integration rate was detected in
      regenerating granulation tissue. Also, one animal showed a high frequency of
      nonhematopoietic Y+ cells in several tissues, including intestinal epithelium and
      mammary gland stroma. In conclusion, circulating cells do not appear significant
      in the development and maintenance of nonhematopoietic bovine tissues, but may be
      important in regeneration and other special conditions.

PMID- 14688388
TI  - Choroidal neovascularization is provided by bone marrow cells.
AB  - Choroidal neovascularization (CNV) is a known cause of age-related macular
      degeneration (ARMD). Moreover, the most common cause of blindness in the elderly
      in advanced countries is ARMD with CNV. It has recently been shown that bone
      marrow cells (BMCs) can differentiate into various cell lineages in vitro and in
      vivo. Adults maintain a reservoir of hematopoietic stem cells included in BMCs
      that can enter the circulation to reach various organs in need of regeneration.
      It has recently been reported that endothelial progenitor cells (EPCs) included
      in BMCs are associated with neovascularization. We examine the role of BMCs in
      CNV using a model of CNV in adult mice. Using methods consisting of fractionated
      irradiation (6.0 Gy x 2) followed by bone marrow transplantation (BMT), adult
      mice were engrafted with whole BMCs isolated from transgenic mice expressing
      enhanced green fluorescent protein (EGFP). Three months after BMT, we confirmed
      that the hematopoietic cells in the recipients had been completely replaced with
      donor cells. We then carried out laser photocoagulation to induce CNV in chimeric
      mice (donor cells >95%). Two weeks after the laser photocoagulation, by which
      time CNV had occurred, immunohistochemical examination was carried out. The
      vascular wall cells of the CNV expressed both EGFP and CD31. These findings
      indicate that newly developed blood vessels in the CNV are derived from the BMCs
      and suggest that the inhibition of EPC mobilization from the bone marrow to the
      eyes could be a new approach to the fundamental treatment of CNV in ARMD.

PMID- 14688389
TI  - Survival and long distance migration of brain-derived precursor cells
      transplanted to adult rat retina.
AB  - Neural precursor cells transplanted to adult retina can integrate into the host.
      This is especially true when the neural precursor rat cell line RN33B is used.
      This cell line carries the reporter genes LacZ and green fluorescent protein
      (GFP). In grafted rat eyes, RN33B cells are localized from one eccentricity to
      the other of the host retina. In the present study, whole-mounted retinas were
      analyzed to obtain a more appropriate evaluation of the amount of transgene
      expressing cells and the migratory capacity of these cells 3 and 8 weeks post
      transplantation. Quantification was made of the number of beta-galactosidase- and
      GFP-expressing cells with a semiautomatized stereological cell counting system.
      With the same system, delineation of the distribution area of the grafted cells
      was also performed. At 3 weeks, 68% of the grafted eyes contained marker
      expressing cells, whereas at 8 weeks only 35% of the eyes contained such cells.
      Counting of marker-expressing cells demonstrated a lower number of transgene
      expressing cells at 3 weeks compared with 8 weeks post-transplantation. The
      distribution pattern of marker gene-expressing cells revealed cells occupying up
      to 21% at 3 weeks and up to 68% at 8 weeks of the entire host retina post
      grafting. The precursor cells survived well in the adult retina although the most
      striking feature of the RN33B cell line was its extraordinary migratory capacity.
      This capability could be useful if precursor cells are used to deliver necessary
      genes or gene products that need to be distributed over a large diseased area.

PMID- 14688390
TI  - Sustained in vitro expansion of bone progenitors is cell density dependent.
AB  - Osteogenic cells are an integral part of the dynamic tissue-remodeling process in
      bone and are potential tools for tissue engineering and cell-based therapies. We
      examined the role of glucocorticoids and cell density in the expansion of primary
      rat calvaria cell populations and osteoprogenitor subpopulations in adherent cell
      culture. Osteoprogenitor response to dexamethasone (dex, a synthetic
      glucocorticoid known to stimulate bone formation in vitro) supplementation and
      long-term osteoprogenitor cell proliferation and differentiation were quantified
      using functional (colony forming unit-osteoblast [CFU-O]) and phenotypic
      analyses. Although osteoprogenitor self-renewal occurred at both standard and
      high initiating cell densities, progenitor cell expansion (measured by changes in
      CFU-O number relative to input) was sustained and dramatically increased at high
      initiating cell densities (30-fold CFU-O expansion for standard-density cultures
      compared with a greater than 10,000-fold CFU-O expansion in high-density
      cultures). Cell density was also found to impact upon the potential of dex to
      recruit additional progenitors towards bone development. These multifaceted
      effects appeared to be independent of cell proliferation rates or population
      phenotypic expression. Together, our results emphasize a roll for cell-cell
      interactions and/or community effects in the control and maintenance of
      progenitor cells during in vitro culture.

PMID- 14688391
TI  - The transcriptome profile of human embryonic stem cells as defined by SAGE.
AB  - Human embryonic stem (ES) cell lines that have the ability to self-renew and
      differentiate into specific cell types have been established. The molecular
      mechanisms for self-renewal and differentiation, however, are poorly understood.
      We determined the transcriptome profiles for two proprietary human ES cell lines
      (HES3 and HES4, ES Cell International), and compared them with murine ES cells
      and other human tissues. Human and mouse ES cells appear to share a number of
      expressed gene products although there are numerous notable differences,
      including an inactive leukemia inhibitory factor pathway and the high
      preponderance of several important genes like POU5F1 and SOX2 in human ES cells.
      We have established a list of genes comprised of known ES-specific genes and new
      candidates that can serve as markers for human ES cells and may also contribute
      to the "stemness" phenotype. Of particular interest was the downregulation of
      DNMT3B and LIN28 mRNAs during ES cell differentiation. The overlapping
      similarities and differences in gene expression profiles of human and mouse ES
      cells provide a foundation for a detailed and concerted dissection of the
      molecular and cellular mechanisms governing their pluripotency, directed
      differentiation into specific cell types, and extended ability for self-renewal.

PMID- 14688392
TI  - Mobilization of myeloma cells involves SDF-1/CXCR4 signaling and downregulation
      of VLA-4.
AB  - Adhesion molecules and stromal cell-derived factor-1 (SDF-1)/CXCR4 signaling play
      key roles in homing and mobilization of hematopoietic stem cells (HSC). Active
      signaling through SDF-1/CXCR4 and upregulation of adhesion molecules are required
      for homing, whereas downregulation of adhesion molecules and disruption of SDF
      1/CXCR4 signaling are required for mobilization of HSC. We studied the surface
      expression of CXCR4 very late activation antigen (VLA)-4 and VLA-5 on myeloma
      cells mobilized with cyclophosphamide and GM-CSF in 12 multiple myeloma patients
      undergoing HSC mobilization for autologous transplantation. We also studied the
      plasma levels of SDF-1 in apheresis collection of these patients. We observed a
      statistically significant decrease in the levels of SDF-1 and surface expression
      of CXCR4 on myeloma cells in four consecutive apheresis collections compared with
      premobilization bone marrow specimens. We also observed a statistically
      significant decrease in surface expression of VLA-4 in myeloma cells in the
      apheresis collections compared with premobilization bone marrow samples.
      Furthermore, myeloma cells derived from apheresis collections had decreased
      adhesion and trans-stromal migration in response to SDF-1, which could be
      reversed by short incubation with interleukin-6. Hence, mobilization of myeloma
      cells involves SDF-1/CXCR4 signaling and downregulation of VLA-4.

PMID- 14688393
TI  - Short-term BMP-2 expression is sufficient for in vivo osteochondral
      differentiation of mesenchymal stem cells.
AB  - Currently available murine models to evaluate mesenchymal stem cell (MSC)
      differentiation are based on cell injection at ectopic sites such as muscle or
      skin. Due to the importance of environmental factors on the differentiation
      capacities of stem cells in vivo, we investigated whether the peculiar
      synovial/cartilaginous environment may influence the lineage specificity of bone
      morphogenetic protein (BMP)-2-engineered MSCs. To this aim, we used the C3H10T1/2
      derived C9 MSCs that express BMP-2 under control of the doxycycline (Dox)
      repressible promoter, Tet-Off, and showed in vitro, using the micropellet culture
      system that C9 MSCs kept their potential to differentiate toward chondrocytes.
      Implantation of C9 cells, either into the tibialis anterior muscles or into the
      joints of CB17-severe combined immunodeficient bg mice led to the formation of
      cartilage and bone filled with bone marrow as soon as day 10. However, no
      differentiation was observed after injection of naive MSCs or C9 cells that were
      repressed to secrete BMP-2 by Dox addition. The BMP-2-induced differentiation of
      adult MSCs is thus independent of soluble factors present in the local
      environment of the synovial/cartilaginous tissues. Importantly, we demonstrated
      that a short-term expression of the BMP-2 growth factor is necessary and
      sufficient to irreversibly induce bone formation, suggesting that a stable
      genetic modification of MSCs is not required for stem cell-based bone/cartilage
      engineering.

PMID- 14688394
TI  - Transplanted bone marrow cells preferentially home to the vessels of in situ
      generated murine tumors rather than of normal organs.
AB  - Transplanted bone marrow-derived (BM) cells have been shown to home into the
      tumor vessels of s.c. implanted tumor models and to functionally contribute to
      tumor neoangiogenesis and tumor growth. However, whether BM cells contribute to
      the vessels of in situ developing tumors remains unknown. We have taken advantage
      of the in situ generation of mammary tumors in transgenic mice carrying the
      polyoma virus middle T oncogene (MMTV-PyVT) to determine whether transplanted BM
      cells home to and incorporate into the intratumoral vessels. Unfractionated BM
      from lacZ+ROSA 26 mice was used to rescue irradiated MMTV-PyVT transgenic mice or
      their wild-type congenics. All transgenic mice were sacrificed when they
      developed easily palpable mammary tumors. BM cells recruited and incorporated
      into the vasculature were identified by coexpression of lacZ and CD31, evidence
      that these cells had a distinctive, elongated appearance and that they lined the
      vessel structures. We found that BM cells home to and incorporate into 1.3% of
      the vessels of all in situ generated mammary adenocarcinomas examined (n=8). In
      contrast, BM cells did not recruit into the vessels of colon or liver of the
      tumor-bearing mice. Whether these cells contribute to new vessel formation via
      vasculogenesis or angiogenesis or simply attach to, and integrate into, the
      growing tips or shafts of pre-existing vessels has to be determined. BM could be
      used as a vehicle for the specific transport of antiangiogenic signals into the
      tumor vascular bed.

PMID- 14688395
TI  - Stable suppression of gene expression in murine embryonic stem cells by RNAi
      directed from DNA vector-based short hairpin RNA.
AB  - Murine embryonic stem (ES) cells are an ideal system for the research of directed
      differentiation in vitro. Long double-stranded RNA, which can induce RNA
      interference (RNAi) effectively in many organisms, has been shown to suppress
      target gene expression efficiently and specifically in undifferentiated ES cells.
      However, it cannot be used in differentiated ES cells due to unspecific
      inhibition of gene expression resulting from the activation of interferon pathway
      following differentiation. Using green fluorescent protein (GFP) as a reporter
      system, we show here that a short hairpin RNA (shRNA) expression vector driven by
      the murine U6 small nuclear RNA promoter can specifically induce potent gene
      knockdown effect (i.e., inhibit GFP expression specifically) when transfected
      transiently into ES cells. Furthermore, when the expression vector is stably
      integrated into the genome of the cell, it can still show specific RNAi effect,
      which can be maintained at least for 10 days. These transfected ES cells showed
      no obvious differences in the morphology or growth rate in culture compared with
      untransfected cells, suggesting that the activation of shRNA-directed RNAi did
      not affect the properties of ES cells and that the RNAi effect in ES cells is
      specific and persistent. Our results prove the feasibility of the U6 promoter
      driven shRNA expression technique to be used to study the function of genes
      expressed in ES cells. These ES cells, after integration of the U6-based RNAi
      vector into their genome, could be used to generate gene knockdown mice.

PMID- 14688396
TI  - Characterization of a lineage-negative stem-progenitor cell population optimized
      for ex vivo expansion and enriched for LTC-IC.
AB  - Current hematopoietic stem cell transplantation protocols rely heavily upon CD34+
      cells to estimate hematopoietic stem and progenitor cell (HSPC) yield. We and
      others previously reported CD133+ cells to represent a more primitive cell
      population than their CD34+ counterparts. However, both CD34+ and CD133+ cells
      still encompass cells at various stages of maturation, possibly impairing long
      term marrow engraftment. Recent studies demonstrated that cells lacking CD34 and
      hematopoietic lineage markers have the potential of reconstituting long-term in
      vivo hematopoiesis. We report here an optimized, rapid negative-isolation method
      that depletes umbilical cord blood (UCB) mononucleated cells (MNC) from cells
      expressing hematopoietic markers (CD45, glycophorin-A, CD38, CD7, CD33, CD56,
      CD16, CD3, and CD2) and isolates a discrete lineage-negative (Lin-) cell
      population (0.10% +/- 0.02% MNC, n=12). This primitive Lin- cell population
      encompassed CD34+/- and CD133+/- HSPC and was also enriched for surface markers
      involved in HSPC migration, adhesion, and homing to the bone marrow (CD164,
      CD162, and CXCR4). Moreover, our depletion method resulted in Lin- cells being
      highly enriched for long-term culture-initiating cells when compared with both
      CD133+ cells and MNC. Furthermore, over 8 weeks in liquid culture stimulated by a
      cytokine cocktail optimized for HSPC expansion, TPOFLK (thrombopoietin 10 ng/ml,
      Flt3 ligand 50 ng/ml, c-Kit ligand 20 ng/ml) Lin- cells underwent slow
      proliferation but maintained/expanded more primitive HSPC than CD133+ cells.
      Therefore, our Lin- stem cell offers a promising alternative to current HSPC
      selection methods. Additionally, this work provides an optimized and well
      characterized cell population for expansion of UCB for a wider therapeutic
      potential, including adult stem cell transplantation.

PMID- 14688397
TI  - Chemokines promote quiescence and survival of human neural progenitor cells.
AB  - Many cell types in the brain express chemokines and chemokine receptors under
      homeostatic conditions, arguing for a role of these proteins in normal brain
      processes. Because chemokines have been shown to regulate hematopoietic
      progenitor cell proliferation, we hypothesized that chemokines would regulate
      neural progenitor cell (NPC) proliferation as well. Here we show that chemokines
      activating CXCR4 or CCR3 reversibly inhibit NPC proliferation in isolated cells,
      neurospheres, and in hippocampal slice cultures. Cells induced into quiescence by
      chemokines maintain their multipotential ability to form both neurons and
      astrocytes. The mechanism of chemokine action appears to be a reduction of
      extracellular signal-related kinase phosphorylation as well as an increase in
      Reelin expression. The inhibitory effects of chemokines are blocked by heparan
      sulfate and apolipoprotein E3 but not apolipoprotein E4, suggesting a regulatory
      role of these molecules on the effects of chemokines. Additionally, we found that
      the chemokine fractalkine promotes survival of NPCs. In addition to their role in
      chemotaxis, chemokines affect both the survival and proliferation of human NPCs
      in vitro. The presence of constitutively expressed chemokines in the brain argues
      that under homeostatic conditions, chemokines promote survival but maintain NPCs
      in a quiescent state. Our studies also suggest a link between inflammatory
      chemokine production and the inhibition of neurogenesis.

PMID- 14688398
TI  - The molecular perspective: protein farnesyltransferase.

PMID- 14688399
TI  - Allan j. Erslev, m.d.: truly a great dane (1919-2003).

PMID- 14688400
TI  - Colorectal carcinoma metastases in liver: laser-induced interstitial
      thermotherapy--local tumor control rate and survival data.
AB  - PURPOSE: To evaluate the local tumor control and survival data for magnetic
      resonance (MR) imaging-guided laser-induced interstitial thermotherapy (LITT) of
      colorectal liver metastases. MATERIALS AND METHODS: MR imaging-guided LITT was
      performed in 603 patients (mean age, 61.2 years) with 1,801 liver metastases of
      colorectal cancer. Survival rates were calculated by means of the Kaplan-Meier
      method. Local tumor control and tumor volume were evaluated with nonenhanced and
      contrast material-enhanced MR imaging. Indications for the procedure were defined
      for patients with five or fewer metastases, none of which were larger than 5 cm
      in diameter. The indications included recurrent liver metastases after partial
      liver resection in 37.6% of study patients, metastases in both liver lobes in
      32.5%, locally nonresectable lesions in 11.3%, general contraindications for
      surgery in 4.6%, and refusal to undergo surgical resection in 13.9%. RESULTS:
      Local recurrence rate at 6-month follow-up was 1.9% (nine of 474) for metastases
      up to 2 cm in diameter, 2.4% (13 of 539) for metastases 2.1-3.0 cm in diameter,
      1.2% (four of 327) for metastases 3.1-4.0 cm in diameter, and 4.4% (13 of 294)
      for metastases larger than 4 cm in diameter. The mean survival rate for all
      treated patients, with calculation started on the date of diagnosis of the
      metastases (which were treated with LITT) was 4.4 years (95% CI: 4.0, 4.8) (1
      year survival, 94%; 2-year survival, 77%; 3-year survival, 56%; 5-year survival,
      37%). Median survival was 3.5 years (95% CI: 3.0, 3.9). Mean survival after the
      first LITT treatment was 3.8 years (95% CI: 3.4, 4.2). Median survival was 2.9
      years (95% CI: 2.4, 3.3). CONCLUSION: MR imaging-guided LITT yields high local
      tumor control and survival rates in well-selected patients with limited liver
      metastases of colorectal carcinoma.

PMID- 14688402
TI  - Colorectal neoplasia screening with CT colonography in average-risk asymptomatic
      subjects: community-based study.
AB  - PURPOSE: To evaluate computed tomographic (CT) colonography as a screening tool
      for average-risk asymptomatic subjects with regard to participation,
      acceptability, and safety. MATERIALS AND METHODS: CT colonography for colorectal
      neoplasia screening was offered to 2,000 subjects aged 50-54 and 65-69 years.
      Only asymptomatic subjects at average risk of colorectal neoplasia were enrolled.
      Participants underwent CT colonography followed by colonoscopy if CT colonography
      findings showed any polyps. Acceptability was measured with a 100-point (0, most
      favorable; 100, least favorable) visual analogue scale (VAS). Chi2 statistic was
      used to compare participation rates among subgroups. Safety of CT colonography
      was evaluated by recording all important adverse events. RESULTS: A total of
      1,452 subjects were eligible for screening. The adjusted participation rate was
      28.4%. Participation was higher in younger subjects and in those from a high
      socioeconomic region. Major reasons for nonparticipation were insufficient time
      and perceived good health. Median VAS scores for pain, general satisfaction,
      embarrassment, and willingness to repeat screening were 13, 6, 8, and 5,
      respectively. Most subjects found CT colonography better than (60%) or same as
      (32%) expected. Ninety-three (27.4%) of 340 subjects were referred for
      colonoscopy, with polyps found in 67 (positive predictive value, 0.73). By
      adopting criteria that a positive finding at CT colonography is that of a single
      polyp larger than 5 mm or multiple polyps larger than 2 mm, 14% of CT
      examinations would have led to colonoscopy; 5.7% of CT findings were false
      positive, with no significant impairment in large polyp detection. There were no
      important adverse events related to CT colonography, although four subjects had
      syncope or presyncope related to bowel preparation. CONCLUSION: Community-based
      colorectal neoplasia screening with CT colonography was accompanied by a
      participation rate that compares favorably with that of similar screening
      programs. CT colonography was highly acceptable to participants.

PMID- 14688401
TI  - Myocardial viability: rapid assessment with delayed contrast-enhanced MR imaging
      with three-dimensional inversion-recovery prepared pulse sequence.
AB  - Contrast-enhanced magnetic resonance (MR) imaging allows detection of nonviable
      myocardium. The authors compared a one-breath-hold three-dimensional inversion
      recovery gradient-echo MR sequence with a multiple-breath-hold two-dimensional
      inversion-recovery gradient-echo MR sequence for the detection of nonviable
      myocardium. On the basis of a quantitative and qualitative approach, total
      myocardial area and contrast material-enhanced area, as well as the presence and
      spatial extent of hyperenhancement, were analyzed separately for each MR image
      obtained with each sequence in 10 patients with chronic ischemic heart disease.
      Findings for total myocardial area and contrast-enhanced area agreed well between
      the two sequences. A high level of agreement was also found for the presence of
      hyperenhancement (kappa = 0.84), while agreement was poor for the transmural
      extent of hyperenhancement (kappa = 0.32), which was attributed to the blurred
      appearance of the three-dimensional MR images. Findings with the one-breath-hold
      three-dimensional MR sequence allow assessment of nonviable myocardium with good
      agreement with those with the multiple-breath-hold two-dimensional MR sequence.

PMID- 14688403
TI  - Appendicitis: evaluation of sensitivity, specificity, and predictive values of
      US, Doppler US, and laboratory findings.
AB  - PURPOSE: To evaluate the sensitivity, specificity, negative predictive value
      (NPV), and positive predictive value (PPV) of ultrasonography (US), Doppler US,
      and laboratory findings in the diagnosis of appendicitis. MATERIALS AND METHODS:
      A total of 125 consecutive patients suspected of having appendicitis were
      prospectively included for US appendiceal (diameter enlarged to 6 mm or greater,
      intraluminal fluid, lack of compressibility) and periappendiceal (periileal
      inflammatory changes, cecal wall thickening, periileal lymph nodes, peritoneal
      fluid) evaluation, Doppler US evaluation (appendiceal wall signal), and
      laboratory assessment (leukocytosis, C-reactive protein [CRP]). Definite
      diagnoses were established at surgery in 61 patients, at endoscopy with biopsy in
      two patients, and at clinical follow-up in 62 patients. RESULTS: The prevalence
      of appendicitis was 46%. The appendix was identified with US in 86% of the
      patients, which included 96% of patients with and 72% of patients without
      appendicitis. The most accurate appendiceal finding for appendicitis was a
      diameter of 6 mm or larger, with a sensitivity, specificity, NPV, and PPV of 98%.
      The lack of visualization of the appendix with US had an NPV of 90%. The most
      accurate periappendiceal finding of appendicitis was the presence of inflammatory
      fat changes, with an NPV of 91% and a PPV of 76%, whereas other findings had both
      NPV and PPV less than 65%. An increase in both white blood cell (WBC) count and
      CRP level had a PPV of 71%, whereas combined normal WBC count and CRP value had
      an NPV of 84%. CONCLUSION: A threshold 6-mm diameter of the appendix under
      compression is the most accurate US finding for appendicitis and has high NPV and
      PPV.

PMID- 14688404
TI  - Ureteral stent placement without postprocedural nephrostomy tube: experience in
      41 patients.
AB  - PURPOSE: To evaluate one-stage antegrade ureteral stent placement without
      postprocedural nephrostomy tube. MATERIALS AND METHODS: Tubeless ureteral stent
      insertion was attempted in 41 (30 men, 11 women; eight, benign obstruction; nine
      outpatients) of 97 adults (56 excluded). Patients were clinically stable with
      known ureteral obstruction and had been referred for antegrade ureteral stent
      insertion. Exclusion criteria were infection, coagulopathy, or emergency cases.
      After renal access was achieved, ureteral stents were inserted. If drainage was
      satisfactory and there was no marked procedural bleeding, all access was removed
      without leaving a nephrostomy tube behind. Technical and clinical success rates
      and complications were assessed with review of radiologic and clinical notes. If
      one-stage stent insertion was unsuccessful, a nephrostomy tube was inserted and
      two-stage stent placement was performed. All 56 patients excluded from this study
      underwent two-stage stent placement. Major complication rate was assessed (Fisher
      test). RESULTS: One-stage stent insertion was technically successful in 36 (88%)
      patients; two with an identifiable risk factor (recent bladder operation,
      retrograde ureteral instrumentation) developed septicemia that required repeat
      nephrostomy tube insertion and 2-8 extra days of hospitalization. Clinical
      success rate was 83% (34 of 41). No major bleeding occurred. In 13 (36%) of 36
      patients, hematuria lasted longer than 24 hours but resolved without further
      intervention or blood transfusion. In those who underwent two-stage stent
      placement (n = 61), technical success rate was 100%, but clinical success rate
      was 98%; one patient developed septicemia, and no major hemorrhage occurred.
      Difference in major complication rate between groups was not significant (6% [two
      of 36] vs 2% [one of 61]; P =.55). CONCLUSION: One-stage tubeless antegrade
      ureteral stent insertion in selected cases showed 88% technical success rate and
      83% clinical success rate, with no major hemorrhage.

PMID- 14688405
TI  - Hybridoma-free generation of monoclonal antibodies.
AB  - Production of monoclonal antibodies requires immortalization of splenocytes by
      somatic fusion to a myeloma cell line partner (hybridomas). Although hybridomas
      can be immortal, they may depend on a feeder cell layer and may be genetically
      unstable. Since the inception of hybridoma technology, efforts to improve
      efficiency and stability of monoclonal antibody-producing cell lines have not
      brought about substantial progress. Moreover, suitable human multiple myeloma
      derived cell lines for the production of human antibodies have been very
      difficult to develop. Here we report a strategy that greatly simplifies the
      generation of antibodies and eliminates the need for hybridomas. We show that
      splenocytes derived from transgenic mice harboring a mutant temperature-sensitive
      simian virus 40 large tumor antigen under the control of a mouse major
      histocompatibility promoter are conditionally immortal at permissive temperatures
      and produce monoclonal antibodies. This simple approach may become a method of
      choice for generation and production of both polyclonal and monoclonal antibodies
      with advantages in high-throughput discovery and antibody-based immunotherapy.

PMID- 14688406
TI  - Detection of bacteria in suspension by using a superconducting quantum
      interference device.
AB  - We demonstrate a technique for detecting magnetically labeled Listeria
      monocytogenes and for measuring the binding rate between antibody-linked magnetic
      particles and bacteria. This sensitive assay quantifies specific bacteria in a
      sample without the need to immobilize them or wash away unbound magnetic
      particles. In the measurement, we add 50-nm-diameter superparamagnetic magnetite
      particles, coated with antibodies, to an aqueous sample containing L.
      monocytogenes. We apply a pulsed magnetic field to align the magnetic dipole
      moments and use a high-transition temperature superconducting quantum
      interference device, an extremely sensitive detector of magnetic flux, to measure
      the magnetic relaxation signal when the field is turned off. Unbound particles
      randomize direction by Brownian rotation too quickly to be detected. In contrast,
      particles bound to L. monocytogenes are effectively immobilized and relax in
      about 1 s by rotation of the internal dipole moment. This Neel relaxation process
      is detected by the superconducting quantum interference device. The measurements
      indicate a detection limit of (5.6 +/- 1.1) x 10(6) L. monocytogenes in our
      sample volume of 20 microl. If the sample volume were reduced to 1 nl, we
      estimate that the detection limit could be improved to 230 +/- 40 L.
      monocytogenes cells. Time-resolved measurements yield the binding rate between
      the particles and bacteria.

PMID- 14688407
TI  - Dominant-negative C/EBP disrupts mitotic clonal expansion and differentiation of
      3T3-L1 preadipocytes.
AB  - Hormonal induction of growth-arrested 3T3-L1 preadipocytes rapidly activates
      expression of CCAAT/enhancer-binding protein (C/EBP) beta. Acquisition of DNA
      binding activity by C/EBPbeta, however, is delayed until the cells synchronously
      enter the S phase of mitotic clonal expansion (MCE). After MCE, C/EBPbeta
      activates expression of C/EBPalpha and peroxisome proliferator-activated receptor
      gamma, which then transcriptionally activate genes that give rise to the
      adipocyte phenotype. A-C/EBP, which possesses a leucine zipper but lacks
      functional DNA-binding and transactivation domains, forms stable inactive
      heterodimers with C/EBPbeta in vitro. Infection of 3T3-L1 preadipocytes with an
      adenovirus A-C/EBP expression vector interferes with C/EBPbeta function after
      induction of differentiation. A-C/EBP inhibited events associated with hormone
      induced entry of S-phase of the cell cycle, including the turnover of p27/Kip1, a
      key cyclin-dependent kinase inhibitor, expression of cyclin A and cyclin
      dependent kinase 2, DNA replication, MCE, and, subsequently, adipogenesis.
      Although A-C/EBP blocked cell proliferation associated with MCE, it did not
      inhibit normal proliferation of 3T3-L1 preadipocytes. Immunofluorescent staining
      of C/EBPbeta revealed that A-C/EBP prevented the normal punctate nuclear staining
      of centromeres, an indicator of C/EBPbeta binding to C/EBP regulatory elements in
      centromeric satellite DNA. The inhibitory effects of A-C/EBP appear to be due
      primarily to interference with nuclear import of C/EBPbeta caused by obscuring
      its nuclear localization signal. These findings show that both MCE and
      adipogenesis are dependent on C/EBPbeta.

PMID- 14688408
TI  - An approach to genomewide screens of expressed small interfering RNAs in
      mammalian cells.
AB  - To facilitate the construction of large genomewide libraries of small interfering
      RNAs (siRNAs), we have developed a dual promoter system (pDual) in which a
      synthetic DNA encoding a gene-specific siRNA sequence is inserted between two
      different opposing polymerase III promoters, the mouse U6 and human H1 promoters.
      Upon transfection into mammalian cells, the sense and antisense strands of the
      duplex are transcribed by these two opposing promoters from the same template,
      resulting in a siRNA duplex with a uridine overhang on each 3' terminus. A single
      step PCR protocol has been developed by using this dual promoter system that
      allows the production of siRNA expression cassettes in a high-throughput manner.
      We have shown that siRNAs transcribed by either the dual promoter vector or siRNA
      expression cassettes can induce strong and gene-specific suppression of both
      endogenous genes and ectopically expressed genes in mammalian cells. Furthermore,
      we have constructed an arrayed siRNA expression cassette library that targets
      >8000 genes with two siRNA sequences per gene. A high-throughput screen of this
      library has revealed both known and unique genes involved in the NF-kappaB
      signaling pathway.

PMID- 14688409
TI  - Demonstration of the Burkitt's lymphoma Epstein-Barr virus phenotype in dividing
      latently infected memory cells in vivo.
AB  - Epstein-Barr virus (EBV) is a herpesvirus that establishes a lifelong, persistent
      infection. It was first discovered in the tumor Burkitt's lymphoma (BL). Despite
      intensive study, the role of EBV in BL remains enigmatic. One striking feature of
      the tumor is the unique pattern of viral latent protein expression, which is
      restricted to EBV-encoded nuclear antigen (EBNA) 1. EBNA1 is required to maintain
      the viral genome but is not recognized by cytotoxic T cells. Consequently, it was
      proposed that this expression pattern was used by latently infected B cells in
      vivo. This would be the site of long-term, persistent infection by the virus and,
      by implication, the progenitor of BL. We now know that EBV persists in memory B
      cells in the peripheral blood and that BL is a tumor of memory cells. However, a
      normal B cell expressing EBNA1 alone has been elusive. Here we show that most
      infected cells in the blood express no detectable latent mRNA or proteins. The
      exception is that when infected cells divide they express EBNA1 only. This is the
      first detection of the BL viral phenotype in a normal, infected B cell in vivo.
      It suggests that BL may be a tumor of a latently infected memory B cell that is
      stuck proliferating because it is a tumor and, therefore, constitutively
      expressing only EBNA1.

PMID- 14688410
TI  - Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced
      breast cancer progression.
AB  - Overexpression of human cyclooxygenase 2 (COX-2) in the mammary glands of
      transgenic mice induces tissue-specific tumorigenic transformation. However, the
      molecular mechanisms involved are not yet defined. Here we show that COX-2
      expressed in the epithelial cell compartment regulates angiogenesis in the
      stromal tissues of the mammary gland. Microvessel density increased before
      visible tumor growth and exponentially during tumor progression. Inhibition of
      prostanoid synthesis with indomethacin strongly decreased microvessel density and
      inhibited tumor progression. Up-regulation of angiogenic regulatory genes in COX
      2 transgenic mammary tissue was also potently inhibited by indomethacin
      treatment, suggesting that prostanoids released from COX-2-expressing mammary
      epithelial cells induce angiogenesis. G protein-coupled receptors for the major
      product, prostaglandin E(2) (PGE(2)) EP(1-4), are expressed during mammary gland
      development, and EP(1,2,4) receptors were up-regulated in tumor tissue. PGE(2)
      stimulated the expression angiogenic regulatory genes in mammary tumor cells
      isolated from COX-2 transgenic mice. Such cells are tumorigenic in nude mice;
      however, treatment with Celecoxib, a COX-2-specific inhibitor, reduced tumor
      growth and microvessel density. These results define COX-2-derived PGE(2) as a
      potent inducer of angiogenic switch during mammary cancer progression.

PMID- 14688411
TI  - Functional brain abnormalities in young adults at genetic risk for late-onset
      Alzheimer's dementia.
AB  - Fluorodeoxyglucose positron emission tomography (PET) studies have found that
      patients with Alzheimer's dementia (AD) have abnormally low rates of cerebral
      glucose metabolism in posterior cingulate, parietal, temporal, and prefrontal
      cortex. We previously found that cognitively normal, late-middle-aged carriers of
      the apolipoprotein E epsilon4 allele, a common susceptibility gene for late-onset
      Alzheimer's dementia, have abnormally low rates of glucose metabolism in the same
      brain regions as patients with probable AD. We now consider whether epsilon4
      carriers have these regional brain abnormalities as relatively young adults.
      Apolipoprotein E genotypes were established in normal volunteers 20-39 years of
      age. Clinical ratings, neuropsychological tests, magnetic resonance imaging, and
      PET were performed in 12 epsilon4 heterozygotes, all with the epsilon3/epsilon4
      genotype, and 15 noncarriers of the epsilon4 allele, 12 of whom were individually
      matched for sex, age, and educational level. An automated algorithm was used to
      generate an aggregate surface-projection map that compared regional PET
      measurements in the two groups. The young adult epsilon4 carriers and noncarriers
      did not differ significantly in their sex, age, educational level, clinical
      ratings, or neuropsychological test scores. Like previously studied patients with
      probable AD and late-middle-aged epsilon4 carriers, the young epsilon4 carriers
      had abnormally low rates of glucose metabolism bilaterally in the posterior
      cingulate, parietal, temporal, and prefrontal cortex. Carriers of a common
      Alzheimer's susceptibility gene have functional brain abnormalities in young
      adulthood, several decades before the possible onset of dementia.

PMID- 14688412
TI  - Shifting foci of hematopoiesis during reconstitution from single stem cells.
AB  - To reveal the early events and dynamics of hematopoietic reconstitution in living
      animals in real-time, we used bioluminescence imaging to monitor engraftment from
      single luciferase-labeled hematopoietic stem cells (HSC) in irradiated
      recipients. Transplanted HSC generated discrete foci in the spleen and bone
      marrow (BM), at a frequency that correlated with BM compartment size. Initially
      detected foci could expand locally, seed other sites in BM or spleen, and/or
      recede with different kinetics. These studies reveal dynamic and variable
      patterns of engraftment from highly purified HSC and indicate that the final
      overall contribution of individual HSC to hematopoietic chimerism does not depend
      on the specific site of initial engraftment and expansion.

PMID- 14688413
TI  - Protein and Chemical Microarrays-Powerful Tools for Proteomics.
AB  - In the last few years, protein and chemical microarrays have emerged as two
      important tools in the field of proteomics. Specific proteins, antibodies, small
      molecule compounds, peptides, and carbohydrates can now be immobilized on solid
      surfaces to form high-density microarrays. Depending on their chemical nature,
      immobilization of these molecules on solid support is accomplished by in situ
      synthesis, nonspecific adsorption, specific binding, nonspecific chemical
      ligation, or chemoselective ligation. These arrays of molecules can then be
      probed with complex analytes such as serum, total cell extracts, and whole blood.
      Interactions between the analytes and the immobilized array of molecules are
      evaluated with a number of different detection systems. In this paper, various
      components, methods, and applications of the protein and chemical microarray
      systems are reviewed.

PMID- 14688415
TI  - Use of Immunomatrix Methods to Improve Protein-Protein Interaction Detection.
AB  - Immunoprecipitation (IP) and coimmunoprecipitation (co-IP) are key techniques for
      studying protein-protein interactions. These methods utilize immobilized protein
      A or protein G to isolate antibody-bound target antigens. The main disadvantage
      of traditional immunoprecipitation and coimmunoprecipitation is that the
      conditions used to elute the precipitated antigen also release the antibody,
      contaminating the antigen and destroying the antibody support. To overcome these
      problems, we describe two methods to generate a reusable antibody support by
      cross-linking the antibody to immobilized protein A or protein G, or by coupling
      it directly to the resin. Our studies have demonstrated that the immobilization
      efficiency for the antibody coupling method was similar for several species of
      antibody. Furthermore, we illustrate that using both methods of antibody
      immobilization yields IP and co-IP results similar to traditional protocols but
      eliminate the antibody heavy and light chains contamination.

PMID- 14688416
TI  - Optimization of Rolling-Circle Amplified Protein Microarrays for Multiplexed
      Protein Profiling.
AB  - Protein microarray-based approaches are increasingly being used in research and
      clinical applications to either profile the expression of proteins or screen
      molecular interactions. The development of high-throughput, sensitive,
      convenient, and cost-effective formats for detecting proteins is a necessity for
      the effective advancement of understanding disease processes. In this paper, we
      describe the generation of highly multiplexed, antibody-based, specific, and
      sensitive protein microarrays coupled with rolling-circle signal amplification
      (RCA) technology. A total of 150 cytokines were simultaneously detected in an RCA
      sandwich immunoassay format. Greater than half of these proteins have detection
      sensitivities in the pg/ml range. The validation of antibody microarray with
      human serum indicated that RCA-based protein microarrays are a powerful tool for
      high-throughput analysis of protein expression and molecular diagnostics.

PMID- 14688414
TI  - Proteomics in Vaccinology and Immunobiology: An Informatics Perspective of the
      Immunone.
AB  - The postgenomic era, as manifest, inter alia, by proteomics, offers unparalleled
      opportunities for the efficient discovery of safe, efficacious, and novel subunit
      vaccines targeting a tranche of modern major diseases. A negative corollary of
      this opportunity is the risk of becoming overwhelmed by this embarrassment of
      riches. Informatics techniques, working to address issues of both data management
      and through prediction to shortcut the experimental process, can be of enormous
      benefit in leveraging the proteomic revolution. In this disquisition, we evaluate
      proteomic approaches to the discovery of subunit vaccines, focussing on viral,
      bacterial, fungal, and parasite systems. We also adumbrate the impact that
      proteomic analysis of host-pathogen interactions can have. Finally, we review
      relevant methods to the prediction of immunome, with special emphasis on
      quantitative methods, and the subcellular localization of proteins within
      bacteria.

PMID- 14688417
TI  - Diagnosis of Ovarian Cancer Using Decision Tree Classification of Mass Spectral
      Data.
AB  - Recent reports from our laboratory and others support the SELDI ProteinChip
      technology as a potential clinical diagnostic tool when combined with $n$ 
      dimensional analyses algorithms. The objective of this study was to determine if
      the commercially available classification algorithm biomarker patterns software
      (BPS), which is based on a classification and regression tree (CART), would be
      effective in discriminating ovarian cancer from benign diseases and healthy
      controls. Serum protein mass spectrum profiles from 139 patients with either
      ovarian cancer, benign pelvic diseases, or healthy women were analyzed using the
      BPS software. A decision tree, using five protein peaks resulted in an accuracy
      of 81.5% in the cross-validation analysis and 80%in a blinded set of samples in
      differentiating the ovarian cancer from the control groups. The potential,
      advantages, and drawbacks of the BPS system as a bioinformatic tool for the
      analysis of the SELDI high-dimensional proteomic data are discussed.

PMID- 14688418
TI  - Relationship between Tear TNF-alpha, TGF-beta1, and EGF levels and severity of
      conjunctival cicatrization in patients with inactive trachoma.
AB  - Tear tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta 1
      (TGF-beta1), and epidermal growth factor (EGF) levels were determined in patients
      with inactive trachoma, and a possible relation between these cytokines and
      conjunctival cicatrization severity was investigated. Forty-four patients with
      inactive trachoma who were admitted to the Department of Ophthalmology at the
      Harran University, Sanliurfa, Turkey, were included in this study. The control
      group consisted of 20 age- and sex-matched healthy subjects. The levels of
      cytokines in tears were measured by ELISA. Tear samples were collected from the
      conjunctival cul-de-sac by means of blunted-tip glass capillary tubes. Eyes with
      inactive trachoma were classified into three subgroups with respect to
      conjunctiva cicatrization: mild, moderate, and severe. In 44 patients with
      inactive trachoma, conjunctival cicatrization was found, including mild (n = 15),
      moderate (n = 16), and severe (n = 13) cases. In patients with inactive trachoma,
      decreases in tear EGF (p = 0.000) concentrations and increases in tear TGF-beta1
      (p = 0.006) and TNF-alpha (p = 0.046) levels with respect to the control group
      were found to be concordant with conjunctival cicatrization severity.
      Statistically significant correlations in tear TNF-alpha (p = 0.018), TGF-beta1
      (p = 0.007), and EGF (p = 0.043) levels were found between mild and severe
      cicatrization groups. TNF-alpha and TGF-beta1 have been implicated in the
      fibrogenic process. Elevated tear levels of inflammatory/fibrogenic cytokines may
      play an important role in scar formation in trachoma. It is possible that
      decreased tear levels of EGF, which may be important for the maintenance of
      corneal epithelial integrity, are related to fibrosis in the lacrimal gland
      ductules.

PMID- 14688419
TI  - A new acrylic tissue adhesive for conjunctival surgery: experimental study.
AB  - PURPOSE: To evaluate the clinical efficacy and the clinical and histopathologic
      tolerance of a new acrylic tissue adhesive (ADAL-2) versus 8/0 polyglactin
      sutures (Vicryl) for its use in conjunctival surgery. METHOD: Experimental study
      performed on New Zealand albino rabbits. The animals were divided into two
      groups. Surgery consisted of a conjunctival peritomy of 8 mm in the superior
      limbus followed by extensive subconjunctival dissection and creation of a flap by
      two radial cuts. The conjunctiva was then attached to the limbus again by the
      proposed acrylic tissue adhesive (ADAL-2) or 8/0 polyglactin suture depending on
      the group. Clinical efficacy of the closure of the conjunctival wound, either
      with adhesives or sutures, and the clinical and histopathologic tolerance were
      also evaluated 1, 7, 28 and 42 days after surgery. RESULTS: Both conjunctival
      surgical closure methods were found to be equal in efficacy concerning their
      ability to fix the conjunctiva to the limbus. There were no significant clinical
      and histopathologic tolerance differences between the new tissue adhesive
      investigated (ADAL-2) and 8/0 polyglactin sutures (Vicryl). Histopathology showed
      no presence of the adhesive 28 days postoperatively. CONCLUSIONS: ADAL-2 tissue
      adhesive is an efficient conjunctival closure method, very well tolerated by the
      ocular surface. Its sealing efficiency and its tolerance are similar to 8/0
      polyglactin sutures. This new acrylic adhesive has a potential as an alternative
      for surgical conjunctival sealing in ophthalmic surgery.

PMID- 14688420
TI  - Improved preparation and preservation of human keratoplasty lenticules.
AB  - PURPOSE: To improve the preparation of lenticules from human cornea and to obtain
      their preservation without loss of viable keratocytes. METHODS: The epithelium
      was manually removed after bathing the surface of the cornea with a solution of
      trypsin and EDTA. Lenticules were prepared by microkeratome resection and viable
      keratocytes were visualized by staining with thiazolyl blue (MTT). RESULTS: The
      pretreatment with trypsin-EDTA allowed the removal of the epithelium without
      damage to the keratocytes and the stroma. When these lenticules were incubated in
      Optisol-GS for 7 days at 4 degrees C, they showed a limited thickness increase
      and a preservation of keratocyte viability. CONCLUSION: This procedure allows the
      preparation of lenticules with viable keratocytes that can be preserved in the
      cold for at least 1 week.

PMID- 14688421
TI  - Effect of acetylcysteine on experimental corneal wounds in dogs.
AB  - The effects of 3, 10 and 20% concentrations of acetylcysteine on experimental
      corneal wound healing in dogs were evaluated. Experimental corneal wounds were
      induced surgically, up to the depth of the anterior third of the stroma, in both
      eyes of 18 dogs. One of the eyes was treated topically with 0.9% NaCl solution
      three times a day. The contralateral eye was treated topically with
      acetylcysteine (3, 10 and 20% concentrations) in each of 6 cases separately.
      Corneal wounds were measured by fluorescein staining every day. The mean time of
      healing in the 3% group was significantly different from control eyes (6.17 +/-
      1.94 days). It was 7.19 +/- 0.75 days in the 20% group and 7 +/- 2 days in the
      10% group. The last two groups were not significantly different from the controls
      (9.67 +/- 3.01 days and 8.17 +/- 3.60 days, respectively).

PMID- 14688422
TI  - Corneal endothelial cytotoxicity of riboflavin/UVA treatment in vitro.
AB  - Recently, we have developed collagen crosslinking induced by combined
      riboflavin/UVA treatment, thus increasing the biomechanical rigidity of the
      cornea to treat progressive keratoconus. The present safety study was performed
      to evaluate possible cytotoxic effects of combined riboflavin/UVA treatment on
      the corneal endothelium in vitro. Endothelial cell cultures from porcine corneas
      were treated with 500 microM riboflavin solution, exposed to various endothelial
      UVA irradiances (370 nm) ranging from 0.1 to 1.6 mW/cm2 for 30 min and evaluated
      24 h later using trypan blue staining and Yopro fluorescence staining. The effect
      of either treatment alone (UVA irradiation ranging from 0.2 to 6 mW/cm2) was also
      tested. An abrupt cytotoxic threshold irradiance level was found at 0.35 mW/cm2
      after combined treatment with riboflavin plus UVA irradiation and at 4 mW/cm2
      with UVA irradiation alone. Riboflavin alone was not toxic. A cytotoxic effect of
      the combined riboflavin/UVA treatment on corneal endothelial cells is to be
      expected with a corneal thickness of less than 400 microm. Therefore, pachymetry
      should be routinely performed before riboflavin/UVA treatment to exclude patients
      at risk.

PMID- 14688423
TI  - Correlation of human age-related cataract with some blood biochemistry
      constituents.
AB  - PURPOSE: The causes of age-related cataract are multifactorial and particular
      consideration has been given to the role of nutritional factors in cataract
      formation. The purpose of this study was to determine the levels of certain blood
      biochemistry constituents in cataract patients and controls and evaluate their
      potential, if any, as identifying risk factors in cataractogenesis. METHODS: This
      is a case-control study where 155 cataract patients and 155 matched controls were
      chosen for evaluation. Cataract subjects were further divided into subgroups
      depending on the location of the cataract. All underwent routine eye examinations
      and blood samples were taken from each one for blood biochemistry analysis
      including serum levels of glucose, urea, cholesterol, triglycerides, total
      protein, albumin, bilirubin, calcium, sodium and potassium and the enzymes
      aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase.
      RESULTS: Mean levels of total protein, bilirubin, calcium, sodium, alanine
      aminotransferase and alkaline phosphatase differed significantly between patient
      and control groups. Patients with posterior subcapsular cataract had
      significantly higher glucose levels (p = 0.05) compared with patients with other
      types of cataract. It was also found that those patients with a cortical cataract
      had the highest level of urea, differing significantly from other subgroups and
      controls. CONCLUSIONS: The mean levels of all constituents under study fell
      within normal body range. However, the levels of several important factors
      demonstrated a positive and significant correlation with cataract. While we do
      not presume to present these results as conclusive, it is possible that a gradual
      and constant variation in these parameters may be predisposing factors in
      cataractogenesis.

PMID- 14688424
TI  - Histological toxicity of grepafloxacin after intravitreal injection.
AB  - PURPOSE: To determine the intravitreal levels of grepafloxacin after intravitreal
      injection of 80 microg and to evaluate the retinal toxicity after intravitreal
      injection of different doses of grepafloxacin in rabbit eyes. METHODS: Fifteen
      female New Zealand white rabbits and 15 female pigmented 'Gigantes de Espana'
      rabbits were injected with 80 microg of grepafloxacin into the vitreous cavity.
      The grepafloxacin concentration was determined with HPLC after 2, 4, 8, 12 and 24
      h. Eighteen female rabbits (9 New Zealand white rabbits and 9 pigmented 'Gigantes
      de Espana' rabbits) were used for a study of toxicity. The rabbits were divided
      into 6 treatment groups: group 1 (3 pigmented rabbits) received an intravitreal
      injection of 80 microg of grepafloxacin in 0.1 ml of saline solution, group 2 (3
      white rabbits) 80 microg of grepafloxacin in 0.1 ml, group 3 (3 pigmented
      rabbits) 800 microg of grepafloxacin, group 4 (3 white rabbits) 800 microg of
      grepafloxacin, group 5 (3 pigmented rabbits) and group 6 (3 white rabbits) 0.1 ml
      of saline solution. Clinical examination was performed prior to injection and 24
      h and 10 days after surgery. The animals were sacrificed 10 days after the
      injection, and the eyes were enucleated and fixed for histopathology. The
      specimens were stained with hematoxylin-eosin and toluidine blue. RESULTS: No
      relevant complications were found during the clinical follow-up. All the eyes
      showed no abnormalities in the histologic evaluation. CONCLUSION: Grepafloxacin
      can be considered as a safe alternative for intravitreal injection for the
      treatment of intraocular infections.

PMID- 14688425
TI  - Effects of topical corticosteroids and nonsteroidal anti-inflammatory drugs on
      prostaglandin e2-induced aqueous flare elevation in pigmented rabbits.
AB  - We evaluated the effects of anti-inflammatory potency of corticosteroids and
      nonsteroidal anti-inflammatory drugs on prostaglandin E2 (PGE2)-induced aqueous
      flare elevation in pigmented rabbits. Transcorneal diffusion of PGE2, 25
      microg/ml (7.09 x 10(-2) mmol/l), with the use of a glass cylinder was achieved
      to produce aqueous flare elevation. Anti-inflammatory drugs were topically
      administered once before PGE2 application. Aqueous flare was measured with a
      laser flare-cell meter. Topical single instillation of dexamethasone sodium
      metasulfobenzoate 0.1%, dexamethasone sodium phosphate 0.1%, and fluorometholone
      0.1% 6 h before PGE2 application inhibited 56, 59, and 43% of flare elevation,
      respectively. Topical single instillation of bromfenac sodium 0.1% and
      pranoprofen 0.1% 1 h before PGE2 application inhibited 33 and 15% of flare
      elevation, respectively. Indomethacin 0.5% did not inhibit flare elevation.
      Corticosteroid eyedrops needed several hours from topical instillation to exhibit
      inhibition of flare elevation. Most nonsteroidal anti-inflammatory drug eyedrops
      inhibited aqueous flare elevation when instilled 1 h before PGE2 application.

PMID- 14688426
TI  - Variants of the myocilin gene in Japanese patients with normal-tension glaucoma.
AB  - Myocilin (MYOC) mutations are associated with juvenile- and adult-onset primary
      open-angle glaucoma (POAG). The purpose of this study was to determine whether
      MYOC gene mutations are associated with normal-tension glaucoma (NTG). The
      prevalence of MYOC mutations was determined in 80 Japanese NTG patients and 100
      control subjects. In addition, the expression of mutant MYOC was determined by
      transforming COS-1 cells with five myocilin variants (R158Q, D208E, I360N, A363T,
      and I477S) and examining whether myocilin was present in the cultured cells
      and/or the culture medium by western blotting. Six different nucleotide sequence
      variants, R46Stop, R76K, R158Q, D208E, A488A, and one in the 3' non-coding
      region, were identified in 80 NTG patients. Variants in codon 46 (R46Stop), codon
      158 (R158Q), and codon 488 (A488A) were not found in the 100 normal controls. The
      frequency of other sequence changes (R76K, D208E, and 3' non-coding) in NTG
      patients did not differ significantly from the frequencies in the control
      subjects. COS-1 cells transfected with the wild type, R158Q, or D208E variants
      secreted myocilin into the culture medium. On the other hand, the detected
      myocilin was significantly reduced in the medium of cells transfected with the
      I360N, A363T, or I477S variants that were previously identified as mutations for
      POAG. Definitive evidence of MYOC variants associated with NTG was not found.

PMID- 14688427
TI  - CS-088, an angiotensin type 1 receptor antagonist, ameliorated the impaired blood
      flow in the optic nerve head of rabbits.
AB  - The effect of CS-088, an angiotensin type 1 receptor antagonist, on optic nerve
      head (ONH) circulation was investigated in anesthetized rabbits. ONH blood flow
      was measured for 3 h using laser Doppler flowmetry. ONH blood flow disturbance
      was induced by intravenous injection of endothelin-1. Blood flow was decreased by
      30%; this decrease was reversed by the injection of CS-088. A single injection of
      CS-088, however, did not alter the baseline ONH blood flow. It is concluded that
      CS-088 can have a beneficial effect on disturbed ONH blood flow.

PMID- 14688428
TI  - Scientific misconduct: from salami slicing to data fabrication.

PMID- 14688429
TI  - Principles of pseudophakic photic phenomena.
AB  - As ophthalmic science develops, the expectations of surgeons and patients
      undergoing cataract or refractive surgery also advance. Good Snellen visual
      acuity is not always an indicator for patient satisfaction, and the surgeon must
      understand the nature and pathogenesis of problems with other less recognised
      visual functions. This paper discusses the phenomenon of unwanted light images
      that may occur after surgery due to optical media imperfections, termed
      pseudophakic photic phenomena. It covers definitions, assessment, high-risk
      groups and possible explanations for the occurrence of such phenomena.

PMID- 14688430
TI  - 20-MHz ultrasound and its value in imaging of lacrimal plugs.
AB  - BACKGROUND: High-frequency B scan ultrasonography is a proven method for the
      assessment of anterior segment diseases. Only few studies have used sonography to
      examine the lacrimal drainage system. We examined the proximal lacrimal drainage
      system by high-resolution 20-MHz ultrasound to verify the possibility to identify
      intracanalicular lacrimal plugs. METHODS: Eight patients who had received 12
      lacrimal plug implants were examined by high-resolution ultrasound. A 20-MHz
      sector scanner was used for detection and localization of 2 types of
      intracanalicular plugs (Herrick) lacrimal silicone plug, Smart trade mark acrylic
      polymer plug) and 1 punctum plug. Ultrasound examinations were performed 1-24
      months after plug placement. Cross-sections of the lacrimal canaliculi were
      obtained. RESULTS: The various intracanalicular implants were successfully viewed
      using the 20-MHz ultrasound sector scanner. Intracanalicular plugs were located
      at the appropriate position as intended. The silicone plugs could be seen as
      areas of higher reflectivity. In contrast, acrylic polymer plugs were seen as low
      reflective inner structures. In a longitudinal echogram, the interface between
      the acrylic polymer plug and the lacrimal canaliculus produced a strong acoustic
      impedance. In patients with an intracanalicular acrylic polymer plug, the caliber
      of the plug could be ascertained and the diameter measured. CONCLUSION: High
      resolution ultrasound with a 20-MHz sector scanner is helpful in detecting
      intracanalicular plugs and is a valuable tool to assess the migration of lacrimal
      plugs through lacrimal canaliculi. A 20-MHz sector scanner can be used to
      identify and locate lacrimal plugs in the proximal drainage system even if
      biomicroscopic signs or clinical data are absent.

PMID- 14688431
TI  - One-year follow-up of selective laser trabeculoplasty in open-angle glaucoma.
AB  - BACKGROUND: Selective laser trabeculoplasty (SLT) targets the pigmented
      trabecular meshwork (TM) cells without damage to the adjacent non-pigmented
      tissue. A study was conducted to evaluate the efficacy and safety of SLT in the
      treatment of uncontrolled open-angle glaucoma. METHODS: In a prospective non
      randomized study 44 eyes of 31 patients with uncontrolled open-angle glaucoma
      were treated with a frequency-doubled, Q-switched Nd:YAG laser. A total of
      approximately 50 spots were placed over 180 degrees of the TM at energy levels
      ranging from 0.7 to 0.9 mJ. Intraocular pressure (IOP) was measured 1, 2, and 24
      h, 1 and 2 weeks and 1, 2, 3, 6, 9, and 12 months after treatment. RESULTS: The
      average pre-operative IOP was 25.6 (SD 2.6) mm Hg (range 22-34). The mean IOP
      reduction from baseline at 24 h, 3, 6 and 12 months was 7.1 mm Hg (SD 3.5) or
      27.6%; 4.2 mm Hg (SD 3.5) or 16.4%; 4.7 mm Hg (SD 4.2) or 18.6%, and 4.4 mm Hg
      (SD 3.8) or 17.1%, respectively. The percent of eyes with IOP reduction of 3 mm
      Hg or more at 3, 6 and 12 months was 66, 78 and 62%. A pressure spike of 8 mm Hg
      or more was detected in 4 eyes (9.1%). Anterior chamber reaction was seen 1 h
      after SLT and was mild to moderate in 16 eyes (40.4%) and marked in 3 eyes
      (6.8%). CONCLUSIONS: SLT has shown reasonable efficacy in lowering IOP over 1
      year follow-up, but there was a tendency for IOP to increase with a longer follow
      up. Long-term follow-up studies with a large sample size are needed to determine
      whether the IOP lowering effect is sustained over time, and to assess the
      efficacy of repeated SLT.

PMID- 14688432
TI  - Visual function, quality of life and patient satisfaction after ophthalmic
      surgery: a comparative study.
AB  - PURPOSE: To compare visual acuity, functional visual performance (VF-14), quality
      of life (QOL) gain (VF-14 gain) and patient satisfaction in a series of patients
      undergoing common types of ophthalmic surgery. METHOD: In a prospective trial,
      the VF-14 QOL questionnaire was administered to 100 patients who underwent
      surgery by one surgeon between May 2001 and April 2002. The following surgeries
      were compared: (1) cataract surgery (non-diabetic patients), (2) cataract surgery
      (diabetic patients), (3) retinal detachment cryo-buckle procedure, (4) pars plana
      vitrectomy, (5) silicone oil removal. VF-14 questionnaire responses, visual
      function and clinical data of all patients were recorded pre-operatively and 1
      and 3 months postoperatively. RESULTS: In comparison to vitreoretinal surgery,
      patients who underwent cataract surgery achieved higher VF-14 scores and required
      less time to recover from the procedure (1 month). The QOL gain (VF-14 gain) was
      significantly higher in patients who had undergone retinal detachment surgery and
      vitrectomy (p < 0.0001). The lowest QOL gain was registered in diabetic patients
      after cataract surgery. Patients with pre-existing eye disease, including
      patients with improved visual acuity, were least satisfied with the final outcome
      of surgery. CONCLUSIONS: The highest VF-14 score was achieved by patients with no
      pre-existing ocular disease, who had undergone cataract surgery. The QOL gain was
      greater in patients with severer initial ocular conditions. Better patient
      satisfaction can be achieved in patients with pre-existing eye disease by
      improving pre-operative patient education.

PMID- 14688433
TI  - Clinicopathological study of the idiopathic macular hole: comparison of
      epiretinal membrane peeling and internal limiting membrane peeling.
AB  - The aim of this study was to identify the internal limiting membrane (ILM) and
      epiretinal membrane (ERM) harvested during macular hole surgery under light
      microscopy and electron microscopy and to evaluate the difference in specimen
      loss rate with and without the aid of indocyanine green (ICG) staining. Thirty
      two consecutive patients (34 eyes) with stage 2-4 macular holes were included.
      ERM peeling (macular hole with ERM) or ILM peeling (macular hole without ERM),
      with or without the use of ICG, was used during macular hole surgery with
      vitrectomy. There were 26 specimens for pathology; 12 specimens (46%) were lost
      during processing. ICG staining did not reduce the specimen loss rate. The
      specimens harvested from intentional ILM peeling displayed a smooth, translucent
      ILM. The specimens harvested from ERM peeling showed moderate cellular
      proliferation abutting on the ILM, and all specimens had an ILM. The pathological
      findings confirmed the clinical observations in all the cases studied. The ILM
      appeared in all specimens harvested by ERM peeling during macular hole surgery.
      ICG staining does not alter the specimen loss rate during pathological
      processing.

PMID- 14688434
TI  - Tropoelastin biosynthesis by corneal cells. Epithelial inhibition of keratocyte
      tropoelastin biosynthesis.
AB  - The vertebrate cornea is an avascular tissue and does not contain elastic fibers.
      We tested the capacity of corneal epithelial cells and stromal keratocytes to
      synthesize tropoelastin. Explant cultures and cell cultures were obtained from
      these two cell types in standard culture conditions. Their elastin-synthetic
      activity was compared to skin explant cultures and to dermal fibroblast cell
      cultures. Both corneal cell types synthesized tropoelastin as shown by the
      incorporation of a radioactive precursor followed by immunoprecipitation of
      tropoelastin. When serial cultures of keratocytes were tested, tropoelastin
      biosynthesis strongly increased after the 3rd passage and was at the 9th passage
      more than the double of that of the first passage. When cocultures were studied
      with or without cell contact, epithelial cells partially inhibited tropoelastin
      biosynthesis by keratocytes. This inhibition was somewhat stronger (-36%, p <
      0.005) with cell-to-cell contact than keeping separate epithelial cells and
      keratocytes bathing in the same medium (-18%, p < 0.005). When human skin
      fibroblasts were substituted for keratocytes with cell-to-cell contact, their
      tropoelastin biosynthesis was also inhibited by corneal epithelial cells (-42%, p
      < 0.005), to the same extent as for keratocytes. In Transwell culture, this
      inhibition was again somewhat lower (-36%, p < 0.005). Some diffusible factor
      produced by epithelial cells is apparently involved. The epithelial inhibition of
      tropoelastin biosynthesis by stromal keratocytes might represent one of the
      mechanisms keeping corneal stroma exempt of elastin fibers.

PMID- 14688435
TI  - PCR with the aqueous humor, blood leukocytes and vitreous of patients affected by
      cytomegalovirus retinitis and immune recovery uveitis.
AB  - PURPOSE: To detect the cytomegalovirus (CMV) genome by PCR in the aqueous humor,
      blood leukocytes and vitreous of patients affected by retinitis and immune
      recovery uveitis (IRU). METHODS: A PCR for CMV genome detection was carried out
      with the aqueous humor, vitreous and blood leukocytes of 54 patients with
      retinitis, including 25 HIV-infected patients presenting CMV retinitis in
      different stages (active lesion 6 cases, healed lesion 14 cases and IRU 5 cases),
      and 29 non-HIV-infected patients (retinitis unrelated to CMV) as negative
      controls. RESULTS: The CMV genome was detected in the vitreous, aqueous humor and
      blood leukocytes of 3 out of 6 HIV-infected patients, presenting active lesions
      in the retina. No CMV genome was detected in the vitreous, aqueous humor and
      blood leukocytes of the 5 HIV-infected patients presenting IRU. CONCLUSIONS: CMV
      genome detection by PCR in aqueous humor could be used as a specific and highly
      predictive technique for confirmation of this infection in the retina. The
      absence of CMV, based on the results of PCR done in clinical samples of the 5 IRU
      cases, does not confirm the hypothesis of a viral replication in the vitreous
      body and aqueous humor of these patients.

PMID- 14688436
TI  - Role of retinal detachment subretinal fluid on extracellular matrix metabolism.
AB  - PURPOSE: To examine the in vitro effects of subretinal fluid (SRF) from patients
      with retinal detachment on extracellular matrix turnover. METHODS: Matrix
      metalloproteinase (MMP) activity was explored by radiolabeled substrate
      degradation and zymography. Human lung fibroblasts were used to analyze SRF
      effects on collagen synthesis and cell proliferation. Transforming growth factor
      beta(2) (TGF-beta(2)) concentration was determined in SRF samples by a
      quantitative sandwich enzyme immunoassay. RESULTS: MMP-2 and MMP-9 gelatinolytic
      activity was observed in all SRF samples. Collagenase activity was not detected
      in SRF from patients with holes and recurrent retinal detachment. All SRF samples
      stimulated fibroblast proliferation and collagen synthesis but SRF samples from
      recurrent retinal detachment patients with previous retinal tears had the largest
      effect with the largest TGF-beta(2) concentration. CONCLUSIONS: The gelatinolytic
      activity found in all SRF samples might be associated with the retinal detachment
      process. Low collagenase activity with an increase in collagen synthesis could
      indicate a risk factor to the development of proliferative vitreoretinopathy.

PMID- 14688437
TI  - Material properties of various intraocular lenses in an experimental study.
AB  - INTRODUCTION: With the recent introduction of small-incision cataract surgery,
      requirements for intraocular lens (IOL) flexibility, strength and hydrophilicity
      have rapidly evolved. The IOL surface, however, remains a critical factor
      influencing uveal biocompatibility. PURPOSE: To objectively quantify factors of
      material properties of various IOLs using contact angle measurements,
      differential scanning calorimetry, dynamic-mechanical measurements and scanning
      electron microscopy. MATERIAL AND METHODS: In our study, 17 currently available
      IOLs were investigated using contact angle measurements to assess hydrophilicity
      and biocompatibility, as well as differential scanning calorimetry for the
      estimation of glass transition temperature. Mechanical capacity and flexibility
      were investigated using dynamic-mechanical measurements. Additional analysis of
      the IOL surface was performed using scanning electron microscopy. RESULTS: The
      contact angle measurements of the studied IOLs revealed similar values within
      each group. The silicone IOLs had values between 106 and 119 degrees. The PMMA
      IOLs were found to have a narrower range of values, between 73.2 and 75.5
      degrees. Lenses made of hydrogel had values between 59.2 and 69.1 degrees. The
      heparin-modified surface showed the lowest contact angle of 56.5 degrees. The
      glass transition temperature was determined by dynamic differential scanning
      calorimetry. The resulting values were between 118.8 and 113.5 degrees C for PMMA
      IOLs, 15.5 and 14.0 degrees C for acrylic IOLs, and -91.7 and -119.6 degrees C
      for silicone IOLs. The dynamic-mechanical measurements revealed that PMMA lenses
      manifested characteristics similar to glass, whereas silicone lenses had
      characteristics similar to rubber. Acrylic lenses were between rubber and glass.
      Scanning electron microscopy revealed smooth dispersion of fibrin on hydrophobic
      IOLs and a relative lack of fibrin adhesion on hydrophilic materials. CONCLUSION:
      These results demonstrate that material properties of various IOL materials are
      consistent within classes of IOL materials. This suggests that the intraoperative
      and postoperative behavior of an IOL is predictable and related to its
      composition, thus allowing surgeons to choose IOLs more appropriate for different
      surgical situations and individual patient characteristics.

PMID- 14688438
TI  - Intravitreal r-TPA and gas injection in traumatic submacular hemorrhage.
AB  - AIM: To present the technique and efficiency of intravitreal recombinant tissue
      plasminogen activator (r-TPA) and gas injection in acute submacular hemorrhage
      (SMH) due to traumatic choroidal rupture. PATIENTS AND METHODS: 0.4 ml of sulfur
      hexafluoride was injected into the vitreous cavity in 2 patients with SMH due to
      traumatic choroidal rupture. In 1 patient gas injection was combined with 50
      microg r-TPA. Both patients were closely followed. RESULTS: Preoperative visual
      acuity was 20/125 in one eye and 20/100 in the other. At the end of the follow
      up, visual acuity had improved to 20/32 in both eyes. CONCLUSION: r-TPA and gas
      injection into the vitreous body may be an efficient therapy in patients with
      submacular hemorrhage due to choroidal rupture.

PMID- 14688439
TI  - Treatment of granular dystrophy with soft contact lenses.
AB  - PURPOSE: To prevent recurrence of granular dystrophy by treatment with soft
      contact lenses. METHODS: After penetrating keratoplasty, a soft contact lens was
      fitted in a 61-year-old woman patient with granular corneal dystrophy. The lens
      was worn continuously for 53 months. RESULTS: No recurrence was observed.
      However, the other eye, which was operated on first and not treated with a
      contact lens, showed severe recurrence of the underlying disease, with granular
      deposits in the stroma. CONCLUSIONS: Fitting of a soft contact lens should be
      considered in this disease after penetrating keratoplasty.

PMID- 14688440
TI  - Surgical management of epiretinal membrane with indocyanine-green-assisted
      peeling.

PMID- 14688441
TI  - Pulsatile luteinizing hormone and follicle-stimulating hormone secretion and
      gonadotropin subunit mRNA levels in the ovariectomized GPR-4 transgenic rat.
AB  - Genetic targeting of the cAMP-specific phosphodiesterase 4D1 (PDE4D1) to
      gonadotropin-releasing hormone (GnRH) neurons in the GPR-4 transgenic rat
      resulted in decreased luteinizing hormone (LH) pulse frequency in castrated
      female and male rats. A similar decrease in the intrinsic GnRH pulse frequency
      was observed in GT1 GnRH cells expressing the PDE4D1 phosphodiesterase. We have
      extended these findings in ovariectomized (OVX) GPR-4 rats by asking what effect
      transgene expression had on pulsatile LH and follicle-stimulating hormone (FSH)
      secretion, plasma and pituitary levels of LH and FSH, and levels of the alpha
      glycoprotein hormone subunit (alpha-GSU), LH-beta and FSH-beta subunit mRNAs. In
      OVX GPR-4 rats the LH pulse frequency but not pulse amplitude was decreased by
      50% compared to wild-type littermate controls. Assaying the same samples for FSH,
      the FSH pulse frequency and amplitude were unchanged. The plasma and anterior
      pituitary levels of LH in the GPR-4 rats were significantly decreased by
      approximately 45%, while the plasma but not anterior pituitary level of FSH was
      significantly decreased by 25%. As measured by real-time RT-PCR, the mRNA levels
      for the alpha-GSU in the GPR-4 rats were significantly decreased by 41%, the LH
      beta subunit by 38% and the FSH-beta subunit by 28%. We conclude that in the
      castrated female GPR-4 rats the decreased GnRH pulse frequency results in
      decreased levels of LH and FSH and in the alpha- and beta-subunit mRNA levels.

PMID- 14688442
TI  - The endogenous cannabinoid, anandamide, activates the hypothalamo-pituitary
      adrenal axis in CB1 cannabinoid receptor knockout mice.
AB  - The purpose of this study was to investigate the effects of the endogenous
      cannabinoid arachidonoyl-ethanolamide, anandamide (AEA), on the activity of the
      hypothalamo-pituitary-adrenal (HPA) axis in cannabinoid receptor (CB(1) receptor)
      inactivated (KO) mice. A low dose (0.01 mg/kg i.p.) of AEA significantly
      increased plasma corticotropin (ACTH) and corticosterone concentrations in both
      wild-type (+/+) and in mutant (-/-) animals. In each case, hormone levels reached
      their peaks at 90 min after AEA administration. In a parallel experiment, AEA
      administration was preceded by the injection of SR 141716A (1.0 mg/kg), a
      selective and potent CB(1) receptor antagonist, or of capsazepine (5.0 mg/kg), a
      potent vanilloid receptor of type 1 (VR1) antagonist. The latter drugs did not
      prevent the effects of AEA on the HPA axis. Using Fos protein
      immunohistochemistry, we observed that the parvocellular part of the hypothalamic
      paraventricular nucleus (PVN) was activated as early as 45 min after AEA
      injection and reached peak levels after 60 min in both +/+ and -/- mice.
      Furthermore, the CB(1) and VR1 receptor antagonists did not block the effects of
      AEA on Fos immunoreactivity. The results strongly support the view that
      activation of the HPA axis produced by AEA possibly occurs via a currently
      unknown (CB(x)) cannabinoid receptor present in PVN.

PMID- 14688443
TI  - Regulation of corticosterone production by vasopressin during water restriction
      and after drinking in rats.
AB  - Plasma vasopressin (VP) and corticosterone have each been shown to be rapidly
      suppressed after drinking in different models of osmotic stimulation in rats;
      however, no causal relationship between these responses has been investigated.
      Studies were performed to determine if plasma VP and corticosterone are reduced
      in parallel after drinking and if manipulation of plasma VP affects plasma, ACTH
      corticotropins and corticosterone in a model of water restriction. A strong
      correlation between changes in plasma VP and corticosterone, but not between
      plasma ACTH and corticosterone, was observed after drinking induced by 6 days of
      water restriction. Similarly, ingestion of isotonic saline resulted in a biphasic
      VP response that was paralleled by adrenal and plasma corticosterone, but not by
      plasma ACTH. Administration of an immunoneutralizing antibody directed against VP
      resulted in a rapid decrease in plasma corticosterone, but not ACTH, in water
      restricted rats, but not in rats receiving water ad libitum. These data suggest
      that during dehydration, elevated plasma VP can stimulate the production of
      corticosterone by the adrenal, independently of ACTH. Moreover, they support the
      hypothesis that the decline in corticosterone after restriction-induced drinking
      is due, in part, to a decline in plasma VP.

PMID- 14688444
TI  - Adrenocorticotropin stress response but not glucocorticoid-negative feedback is
      altered by prenatal morphine exposure in adult male rats.
AB  - The present study was designed to investigate the effects of prenatal morphine
      exposure on the hypothalamic-pituitary-adrenal (HPA) axis-regulated stress
      responses by measuring restraint stress-induced changes in the
      adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels. In
      experiment 1, plasma levels of ACTH and CORT in prenatally morphine-, saline
      exposed and control male rats were determined before and at several times after
      restraint stress. There were no statistically significant differences in plasma
      ACTH and CORT levels before restraint stress between the groups. However,
      prenatal morphine exposure dampened the stress-induced increase and spontaneous
      recovery of ACTH levels after the restraint stress. There were no differences in
      plasma CORT levels between the three groups either before or at any time after
      restraint stress. Experiment 2 was designed to investigate the sensitivity of
      negative feedback of glucocorticoids using the dexamethasone (DEX) suppression
      test. DEX was administered at different doses (0.001, 0.01, 0.1 and 1.0 mg/kg)
      and ACTH and CORT plasma levels were measured before and at several times after
      restraint stress in prenatally morphine- and saline-exposed males. DEX
      pretreatment eliminated the differences observed in ACTH responses to stress in
      morphine- and saline-exposed males. DEX pretreatment dose dependently suppressed
      the restraint stress-induced increased plasma ACTH concentration. In plasma CORT
      levels, DEX pretreatment dose dependently suppressed the restraint stress-induced
      increased plasma CORT concentration regardless of prenatal drug exposure. Thus,
      the present study demonstrates that prenatal morphine exposure alters the ACTH
      and CORT responses to stress but not the sensitivity of negative feedback of
      glucocorticoids.

PMID- 14688445
TI  - Hypothalamic neuropeptide Y/Y1 receptor pathway activated by a reduction in
      circulating leptin, but not by an increase in circulating ghrelin, contributes to
      hyperphagia associated with triiodothyronine-induced thyrotoxicosis.
AB  - Food intake is regulated by hypothalamic neuropeptides which respond to
      peripheral signals. Plasma ghrelin and leptin levels reflect peripheral energy
      balance and regulate hypothalamic neuropeptides such as neuropeptide Y (NPY), pro
      opiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART),
      melanin-concentrating hormone (MCH), and orexins. Thyroid hormone stimulates food
      intake in humans and rodents. However, the mechanisms responsible for this
      stimulation have not been fully elucidated. To investigate the hyperphagic
      response to triiodothyronine (T(3))-induced thyrotoxicosis, adult male rats were
      studied 7 days after daily intraperitoneal injections of T(3) or vehicle. T(3)
      treated rats were markedly hyperphagic. During this hyperphagia, plasma leptin
      levels were markedly decreased. However, the expression of the ghrelin gene in
      the stomach and the plasma ghrelin concentrations did not differ between the 2
      groups. Hypothalamic NPY mRNA levels were significantly increased and associated
      with a marked decreased in both hypothalamic POMC and CART mRNA levels in the
      T(3)-treated rats. Hypothalamic MCH and orexin mRNA levels did not differ between
      the 2 groups. In addition, hyperphagia was partially reversed by
      intracerebroventricular administration of the NPY Y1 receptor antagonist
      BIBO3304. Therefore, the decreased plasma leptin levels could contribute to
      hyperphagia in T(3)-induced thyrotoxicosis. However, plasma ghrelin levels did
      not contribute to this hyperphagia.

PMID- 14688446
TI  - Evaluation of the role of melanocortin 3 and 4 receptors in leptin-stimulated and
      spontaneous growth hormone secretion in rats.
AB  - It has been reported that the melanocortin 4-receptor (MC4-R) may act downstream
      of leptin to mediate its effects on food intake and several neuroendocrine
      functions (the reproductive system, the hypothalamo-pituitary-thyroid axis, and
      prolactin secretion). However, no previous study examined whether MC4-R mediates
      leptin stimulatory actions on growth hormone (GH) secretion, or whether MC4-R
      signaling is involved in spontaneous pulsatile GH release in fed rats. Therefore
      in this study we examined the involvement of both MC3-R and MC4-R (the
      predominant MC-R subtypes expressed in the brain) in these two aspects of GH
      secretion in freely-moving male rats. In both fed and 3-day fasted rats, plasma
      GH levels were determined every 15 min over 5 h after single
      intracerebroventricular injections of the following substances or vehicle.
      Fasting diminished and leptin (0.3 nmol) reinstated the GH pulse amplitude
      without affecting the pulse frequency. Neither HS014 (1.0 nmol, a selective MC4-R
      antagonist) nor agouti-related peptide (1.0 nmol, a non-selective MC3/4-R
      antagonist) was effective in altering leptin-stimulated or spontaneous GH
      secretion. In addition, neither melanotan-II (1.0 nmol, a non-selective MC3/4-R
      agonist) nor gamma(1)-melanocyte-stimulating hormone (10 nmol, a selective MC3-R
      agonist) affected significantly GH release in fasted rats. We have previously
      demonstrated that stimulation or blockade of MC4-R, achieved by the same drug
      dosage as in this study, significantly affect luteinizing hormone and prolactin
      secretion in rats. The present results thus suggest that neither MC4-R nor MC3-R
      is involved in leptin-stimulated or spontaneous GH secretion, or at least that
      the level of MC4-R involvement in GH secretion is much lower than that in
      luteinizing hormone and prolactin release regulation.

PMID- 14688448
TI  - Classifying hepatitis B virus genotypes.
AB  - In 1988, hepatitis B virus (HBV) was classified into four genotypes by a sequence
      divergence in the entire genome exceeding 8%, and designated by capital letters
      of the alphabet from A to D. There are seven genotypes of HBV (A-G) at present,
      and an eighth is on the horizon. They have an uneven geographical distribution,
      and only a few of them are prevalent in a given area of the world. Thus genotype
      A is frequent in northwest Europe, Sub-Saharan Africa, India and the North,
      Central and South America, B as well as C are common in Southeast Asia and
      Oceania, and D is prevalent in the Mediterranean area, Central Asia and South
      America. Genotype E is restricted to West Africa, and F is localized in Central
      and South America. The distribution of genotype G added to the alphabet list very
      recently has yet to be determined. Coinfection with HBV of distinct genotypes is
      not infrequent and found in about 10% of infected individuals, and is responsible
      for intertypic recombination of HBV genomes. The mutation for a stop codon in the
      precore region (G1896A) for aborting the translation of hepatitis B e antigen
      (HBeAg) is prohibited in HBV genomes of genotype A, as well as some of genotypes
      C and F, because they possess C at position 1858 that makes a Watson-Crick pair
      with G at position 1896. Hence, seroconversion to antibody to HBeAg is forbidden
      or delayed in individuals who carry them. Evidence is accumulating as regards the
      influence of HBV genotypes on the progression of chronic hepatitis B and response
      to antiviral therapies. HBV isolates even of the same genotype can differ in
      virological and clinical characteristics, and therefore, the genotype needs to be
      classified further into subtypes, especially if they are clinically relevant.

PMID- 14688447
TI  - Blood glucose is correlated with cerebrospinal fluid neurotransmitter
      metabolites.
AB  - Medications which influence monoaminergic neurotransmission can also have an
      effect on glucose regulation. In order to better understand the role of central
      monoaminergic neurotransmission in blood glucose homeostasis, we explored the
      relation between blood glucose and cerebrospinal fluid metabolite concentrations
      of monoaminergic neurotransmitters. Under stringently controlled resting
      conditions, we measured fasting blood glucose and performed lumbar punctures on
      41 healthy participants. Peripheral blood glucose concentrations were
      significantly correlated with the cerebrospinal fluid concentrations of the
      dopamine metabolite, homovanillic acid and the noradrenaline metabolite, 3
      methoxy-4-hydroxyphenylglycol. These correlations may represent a homeostatic
      relation between brain neurotransmitter activity and blood glucose.

PMID- 14688449
TI  - Influence of the hepatitis B e antigen/anti-HBe status on the response to
      lamivudine.
AB  - OBJECTIVE: The optimal therapeutic regimen of lamivudine for chronic hepatitis B
      is not agreed upon, especially with reference to hepatitis B e antigen (HBeAg) or
      the corresponding antibody (anti-HBe) in sera of patients. METHODS: We analyzed
      249 Japanese patients with chronic HBV infection who were treated with lamivudine
      for more than 12 months. HBeAg was detected in sera from 117 of them (47%). HBV
      DNA sequences in serum samples from the pretreatment period and during therapy
      were amplified by polymerase chain reaction, and analyzed for mutations. RESULTS:
      Lamivudine normalized serum levels of alanine aminotransferase at 6 and 12
      months, and suppressed serum HBV DNA to levels undetectable by the bDNA method in
      most patients. Lamivudine suppressed HBV DNA levels to a greater extent in
      patients with anti-HBe than HBeAg. In patients treated with lamivudine for 5
      years, HBV mutants with mutations in the precore region and core promoter
      reverted to the wild-type in some of them within 1 year. CONCLUSION: Lamivudine
      induces a better response in patients without than in those with HBeAg. It
      initially selects the wild-type HBV from among precore or core promoter mutants.

PMID- 14688450
TI  - Viral breakthrough during lamivudine therapy for chronic hepatitis B.
AB  - The mainstay of therapy for patients with chronic hepatitis B is inhibition of
      the replicative cycle of hepatitis B virus (HBV) in hepatocytes. Antiviral agents
      have different potencies. The measurement of HBV DNA in serum can monitor the
      potency of these therapeutic agents. Viral breakthrough may occur during therapy,
      which is defined as an abrupt increase in serum HBV DNA levels after a period of
      persistent suppression. The accuracy of HBV DNA detection depends on the
      sensitivity of assays. The third-generation quantitative assays have a lower
      limit of detection in ranges similar to those of quantitative PCR reaching 2
      log10 copies/ml. The sensitive assays also give insight into the pathophysiology
      of chronic hepatitis B. Monotherapy usually suppresses the viral replication
      inadequately. It only brings about a reduction of serum HBV DNA levels from 8 to
      4 log10 copies/ml. In other words, HBV is not completely eliminated. Viral
      breakthrough occurs with noncompliance to therapy and, also, when drug-resistant
      mutants emerge. Mutations in the YMDD motif of HBV polymerase lead to resistance
      to antivirals, such as lamivudine and famciclovir. In clinical practice, the
      diagnosis and management of viral breakthroughs are problematic and
      controversial. Due to advances in therapy, more potent agents are available such
      as adefovir dipivoxil that seldom induce viral breakthroughs for up to 134 weeks
      of therapy. Potent antiviral agents also lead to the decline of cccDNA in
      hepatocytes. Combination therapies may further improve efficacy and avoid viral
      breakthroughs.

PMID- 14688451
TI  - Subclones of drug-resistant hepatitis B virus mutants and the outcome of
      breakthrough hepatitis in patients treated with lamivudine.
AB  - Breakthroughs during lamivudine therapy were assessed according to hepatitis
      flares and mutational polymorphism of hepatitis B virus (HBV) infecting patients.
      Of 42 patients with chronic hepatitis B and positive for hepatitis B e antigen in
      serum, 13 (30%) harbored HBV mutants with lamivudine resistance after a mean
      duration of 29 months on lamivudine. The virological breakthrough occurred 14.5
      months after the start of lamivudine treatment, and all the patients with it
      developed breakthrough hepatitis 3 months later. The clinical course of
      breakthrough hepatitis was self-limited except in one patient who had already
      developed cirrhosis at the baseline. One year after breakthrough hepatitis, serum
      ALT, albumin, prothrombin time and platelet counts were maintained well on
      conventional treatments without resorting to interferon. Major HBV mutants during
      breakthrough hepatitis were those with M552I in the YMDD motif of viral DNA
      polymerase/reverse transcriptase in 7 patients (54%), M552I/L528M in 4 patients
      (31%) and M552V/L528M in 2 patients (15%). There were no patients in whom
      mutations at nucleotide 529 occurred including the 2 who later developed
      hepatocellular carcinoma. There was no clear relationship between distinct
      mutational patterns and clinical courses. Further studies are needed for making
      out the effects of lamivudine-resistant mutants on clinical outcomes, taking into
      considerations genotypes of HBV.

PMID- 14688452
TI  - Rare quasispecies in the YMDD motif of hepatitis B virus detected by polymerase
      chain reaction with peptide nucleic acid clamping.
AB  - The emergence of drug-resistant mutants of hepatitis B virus (HBV) is a serious
      problem during antiviral therapy of patients with chronic hepatitis B. Lamivudine
      resistant mutants with a mutation in the YMDD motif of reverse transcriptase of
      HBV emerge in approximately one half of the treated patients within 5 years. To
      date, the detection of YMDD mutants by polymerase chain reaction (PCR) with
      peptide nucleic acid (PNA) clamping is most sensitive. In this study, the
      performance of this method was evaluated in various clinical settings. The PCR
      PNA method was able to detect the emergence of YMDD mutants 2-3 months earlier
      than the previously developed method involving restriction fragment length
      polymorphism. Further, rare quasispecies were detected by PCR-PNA in patients
      with chronic hepatitis B who were positive for hepatitis B e antigen (HBeAg).
      Many previously unrecognized mutants, such as those with YLDD and YMED, were
      found in them. Although precise sequence analyses of 10 patients identified YVDD
      and YIDD sequences in 6 of them, only 1 patient had a typical YVDD sequence that
      was identical with that in the reported lamivudine-resistant strain. All HBV
      mutants with the YIDD sequence accompanied stop codon(s) in the overlapping
      envelope (S) gene, suggesting that these strains would have no relevance as
      regards the emergence of lamivudine resistance. These results suggest that it
      would be difficult to detect lamivudine-resistant mutants before the therapy and
      that they would have a greater ability to evade the attack of antiviral drugs by
      frequent nucleotide substitutions than previously expected.

PMID- 14688453
TI  - Short-term lamivudine therapy in patients with chronic hepatitis B.
AB  - Lamivudine is a nucleoside analogue with potent inhibitory effects on hepatitis B
      virus (HBV) polymerase/reverse transcriptase activity. The rate of hepatitis B e
      antigen (HBeAg) seroconversion in a large series of Asian patients treated with
      lamivudine 100 mg daily for 1 year was only 16% and the incidence of YMDD mutants
      was 14%. Further analysis of this Asian trial has shown that patients with a
      pretreatment alanine aminotransferase (ALT) level higher than 5-fold the upper
      limit of normal (ULN) have a much higher HBeAg seroconversion rate as compared
      with patients with a pretreatment ALT level <2 x upper limit of normal (64 vs.
      5%; p < 0.001). In order to avoid the development of YMDD mutants, we selected
      186 patients with acute exacerbation for treatment with lamivudine during 9
      months, if possible, and not more than 15 months. They were all seropositive for
      both hepatitis B surface antigen and HBeAg for more than 6 months and also had
      serum HBV DNA; 138 (74%) of them were male. HBV genotypes were A in 2 (1%), B in
      115 (62%), C in 65 (35%), D in 2 (1%) and F in the remaining 2 (1%). Four
      patients (2%) had liver cirrhosis. They had mean pretreatment levels of ALT at
      608 IU/l (range: 184-2,400 IU/l), total bilirubin at 1.5 mg/dl (0.3-14.8 mg/dl),
      and HBV DNA at 2,246 pg/ml (0.5-25,903 pg/ml). After a median of 8.2 months (3-15
      months) on lamivudine, 96 patients (51%) achieved HBeAg seroconversion, while the
      other 90 (48%) patients did not. Genotype B was detected comparably frequently in
      seroconverters and nonconverters (63 vs. 61%). During 1-year follow-up after
      withdrawal of lamivudine, 56 (58%) of the 96 seroconverters experienced flare-ups
      with ALT levels elevated higher than 5 x ULN in 50 (89%). Of 90 patients who
      remained HBeAg-positive, in contrast, 80 (86%) experienced ALT flares (with ALT
      >5 x ULN in 84%) within 1 year. YMDD mutants did not develop in any of these 186
      patients during the course of lamivudine therapy. In conclusion, short-term
      lamivudine therapy in patients with chronic active hepatitis B can reduce the
      incidence of YMDD mutants and achieve an acceptable HBeAg seroconversion rate.
      However, the relapse rate was high (60% during 1-year follow-up). Further study
      is needed to establish how to improve a sustained HBeAg response.

PMID- 14688454
TI  - Short-term lamivudine for the treatment of chronic hepatitis B.
AB  - Short-term lamivudine and its withdrawal were evaluated as regards an
      immunomodulatory therapy of chronic hepatitis B. Lamivudine was given for 3 or 6
      months to 23 patients with chronic hepatitis B who were infected with hepatitis B
      virus (HBV) genotype C, including 15 with hepatitis B e antigen (HBeAg) and 8
      without it. It decreased serum levels of alanine aminotransferase (ALT) and HBV
      DNA in HBeAg-positive patients. Flare-ups of ALT and HBV DNA after treatment were
      observed in most patients, and 4 of the 12 (33%) patients with 6-month lamivudine
      treatment remained in remission 6 months after withdrawal of the therapy. In
      HBeAg-negative patients, however, flare-ups of ALT and HBV DNA were mild.
      Normalization of ALT and a decrease in serum HBV DNA were accomplished in 6 of
      the 9 (75%) patients. Breakthroughs or serious side effects were not observed in
      any patients. Short-term lamivudine is safe and may offer a therapeutic option to
      patients with chronic hepatitis B.

PMID- 14688455
TI  - Hepatitis B genotypes in chronic hepatitis B and lamivudine therapy.
AB  - The influence of hepatitis B virus (HBV) genotypes on the natural history and the
      response to treatment of patients with chronic hepatitis B are of potential
      interest. Compared to the patients with HBV genotype C, those with genotype B
      were of a younger age and had a higher cumulative rate of hepatitis B e antigen
      (HBeAg) seroconversion during the initial 6 years of follow-up. The earlier HBeAg
      seroconversion in the patients with genotype B, however, did not provide them
      with a benefit in terms of a reduced risk of developing long-term complications.
      The response to lamivudine therapy was evaluated in 21 patients infected with HBV
      genotype B (all of subtype Ba) and 61 with genotype C. There were no differences
      in the virological response to lamivudine therapy, based on the reduction in
      median logarithmic HBV DNA titer as well as alanine aminotransferase (ALT)
      levels, normalization of ALT and the rate of HBeAg seroconversion between the
      patients with genotypes B and C. No differences were noted either, in the
      frequency of YMDD mutants at week 52 or the cumulative risk of HBV DNA
      breakthroughs with YMDD mutations during long-term lamivudine therapy (median
      37.5 months). In conclusion, there is no influence of HBV genotypes on the
      development of long-term complications and lamivudine therapy in Hong Kong.

PMID- 14688456
TI  - Continued lamivudine therapy in patients with chronic hepatitis B.
AB  - From September 1995 through April 2002, 286 patients with chronic hepatitis B
      were started on lamivudine at the Toranomon Hospital in Tokyo, Japan, and most of
      them continued with it. At present, 16 patients received lamivudine for 5 years,
      7 of whom for 7 years or longer. YMDD mutants increased gradually and developed
      in 69% of them during the 7 years on lamivudine. Biochemical and virological
      responses were achieved in 9 of the 16 patients (56%) at 5 years, and in 4 of the
      7 patients (57%) at 7 years. Histological assessments were performed at 3 years
      in the 16 patients and further at 4 and 7 years in the 7 patients.
      Necroinflammatory changes improved remarkably with a decrease in the total
      histological activity score from 11.3 +/- 3.0 to 4.1 +/- 1.7 (p < 0.0001) at 3
      years in the 16 patients. Histological improvements continued in 4 of the 7
      patients (57%) at 7 years on lamivudine, while the pathology was unchanged in 2
      patients (29%) and aggravated in the remaining 1 patient (14%). Severe acute
      exacerbation of hepatitis developed in 1 patient, who received additional
      interferon-alpha therapy to cope with it. Based on my experience, the
      continuation of lamivudine in patients with chronic hepatitis B benefits
      approximately two thirds of them with persistent virological and biochemical
      responses accompanied by histological improvements. Breakthrough hepatitis
      induced by YMDD mutants along the way in a small number of patients needs to be
      diagnosed promptly by regular monitoring for transaminases and, if it develops,
      it can be treated with interferon or other antiviral agents.

PMID- 14688457
TI  - Lamivudine therapy for decompensated liver cirrhosis related to hepatitis B virus
      infection.
AB  - Chronic hepatitis B virus (HBV) infection is the major cause of chronic liver
      disease worldwide. Although the clinical course of HBV infection varies widely,
      the prognosis of decompensated liver cirrhosis is quite poor and the 5-year
      survival rate has been estimated to be only 14-35%. While the ultimate treatment
      of decompensated cirrhosis is orthotopic liver transplantation (OLT), recent
      studies have suggested that lamivudine can also improve the clinical outcomes in
      this group of patients. Lamivudine rapidly suppresses HBV replication and can
      improve several parameters of liver function tests and afford prolonged periods
      of pretransplantation survival. However, the proportion of clinical improvement
      as defined by a decrease in Child-Pugh score as well as the prolonged survival
      rate varied widely from study to study. These discrepancies might result from
      differences in the severity of cirrhosis at entry, the presence of active viral
      replication or inflammation, and the proportions of patients who received OLT
      during the study period. Overall, about half of the patients achieved a clinical
      improvement with lamivudine therapy. However, data are still lacking on whether
      lamivudine can prolong survival before OLT and even replace OLT. Most of the
      deaths or clinical improvement occurred or started to occur within the first 6
      months of treatment. Therefore, OLT should be actively considered in patients
      with risk factors for early mortality or those without clinical improvement
      within the first 6 months of lamivudine treatment.

PMID- 14688458
TI  - Lamivudine therapy for Japanese patients with cirrhosis B.
AB  - OBJECTIVE: The aim of this study was to investigate the emergence of YMDD mutants
      in patients with chronic hepatitis B during lamivudine therapy and to compare the
      emergence patterns of YMDD mutants in cirrhotic and noncirrhotic patients.
      METHODS: Eighteen cirrhotic and 37 noncirrhotic patients with chronic hepatitis B
      were studied. The emergence of YMDD mutants was determined before, as well as at
      1, 3, 6, 9 and 12 months after treatment using a highly sensitive method based on
      polymerase chain reaction. RESULTS: Although YMDD mutants were elicited early,
      the emergence of YMDD mutants was not always associated with breakthrough
      hepatitis. YMDD mutants appeared in cirrhotic and noncirrhotic patients: in 22
      and 8% at 1 month, 13 and 21% at 3 months, 46 and 19% at 6 months, 30 and 19% at
      9 months, and 83 and 27% at 12 months, respectively. CONCLUSION: YMDD mutants
      emerge more frequently in cirrhotic than noncirrhotic patients during the early
      period on lamivudine treatment. The highly sensitive method may be useful for
      monitoring the development of YMDD mutants in patients with chronic hepatitis B
      during lamivudine therapy.

PMID- 14688459
TI  - Hepatitis B virus genotypes and hepatocellular carcinoma in Taiwan.
AB  - With phylogenetic analysis of hepatitis B virus (HBV) isolates, eight different
      genotypes (A to H) have been recognized worldwide. The impact of HBV genotypes on
      the clinical aspects of HBV infection in Taiwan, including the clinical outcome
      of chronic infection and therapeutic response to antiviral treatments, has been
      clarified. Our data showed that genotypes B and C are the predominant HBV strains
      in Taiwan, and genotype C is associated with more severe liver disease including
      cirrhosis and hepatocellular carcinoma (HCC), whereas genotype B is associated
      with the development of HCC in young noncirrhotic patients. Serologically,
      genotype C tends to have a higher frequency of hepatitis B e antigen (HBeAg)
      positivity and a higher serum HBV DNA level than genotype B. In addition,
      genotype C patients, compared to genotype B patients, have a delayed HBeAg
      seroconversion in the immune clearance phase of chronic HBV infection.
      Virologically, genotype C bears a higher frequency of basal core promoter
      mutation than genotype B. Our recent data further indicated that patients with
      basal core promoter mutation are significantly more associated with the
      development of HCC than those without, which applies to both genotypes B and C.
      In addition, the prevalence of basal core promoter mutation in young HCC patients
      is comparable to older HCC patients but is significantly higher than that in age
      matched inactive carriers, irrespective of genotypes. Although superinfection of
      HBV on hepatitis B carriers indeed occurs in Taiwan, it is rarely associated with
      acute exacerbations. As to the response to antiviral treatments, genotype C is
      associated with a lower response rate to interferon therapy compared to genotype
      B. In addition, genotype B seems to have a better virological response to
      lamivudine as compared to genotype C, but both genotypes have a similar risk in
      the development of lamivudine resistance. These lines of evidence highlight the
      remarkable differences in the clinical and virological characteristics between
      Taiwanese patients infected with different genotypes. In conclusion, pathogenic
      and therapeutic differences do exist among HBV genotypes in Taiwan, and
      determining the genotype in patients with chronic HBV infection would help gain
      further information in anthropologic, clinical, virological and prognostic
      investigations.

PMID- 14688460
TI  - Hepatitis B virus genotypes and hepatocellular carcinoma in Japan.
AB  - Hepatitis B virus (HBV) is one of the major causative agents of hepatocellular
      carcinoma (HCC) in Southeast Asia where HBV genotype B (HBV/B) and genotype C
      (HBV/C) are prevalent. Clinical and virological differences were evaluated
      between HCC patients in Japan and Taiwan, all of whom were infected with HBV/B
      and HBV/C. In Japan, the prevalence rates of HBV/B and HBV/C were 12 and 85%,
      respectively, in patients with chronic HBV infection, which is similar to those
      of 13 and 86% in patients with HCC. In the HCC patients with HBV/B, the mean age
      was 70 years and higher than that of 55 years in those with HBV/C. In Taiwan,
      however, HBV/B was detected in 61% and HBV/C in 31% of patients with HCC.
      Furthermore, the mean age of HCC patients with HBV/B in Taiwan was 50 years and
      younger compared to the 59 years of those with HBV/C. These differences may be
      explained by a distinct distribution of subtypes of HBV/B between the two
      countries. In Taiwan as well as in most Asian countries only the subtype Ba of
      HBV/B is found, while the majority of Japanese patients with HBV/B have the
      subtype Bj. Although the risk factors associated with HCC should be investigated
      with respect to host and environmental factors, the differences in genotypes and
      subtypes of HBV would need to be taken into consideration in etiological and
      clinical studies on HCC.

PMID- 14688461
TI  - Antivirals for the treatment of chronic hepatitis B: current and future options.
AB  - Despite effective vaccination programmes, new hepatitis B virus (HBV) infections
      remain common and there are many millions of individuals already infected.
      Therapeutic agents are needed to reverse existing liver disease and prevent
      future disease progression. This article reviews recently published clinical data
      on the two currently available antivirals for the treatment of chronic hepatitis
      B infection, lamivudine and adefovir dipivoxil. Lamivudine, a nucleoside
      analogue, is currently the only licensed antiviral for the treatment of chronic
      hepatitis B in Asia. Extensive clinical trials have shown that lamivudine is
      effective and well tolerated in a wide range of patients. YMDD variants have been
      identified in some patients with reduced sensitivity to lamivudine after extended
      therapy. Adefovir dipivoxil, a nucleotide analogue, will soon be commercially
      available in Asia. Adefovir dipivoxil 10 mg is well tolerated and is as effective
      as lamivudine in reducing serum HBV DNA and alanine aminotransaminase levels and
      increasing seroconversion in patients with hepatitis B e antigen. No adefovir
      resistant mutants have been reported during 48-week clinical trials. The addition
      of adefovir dipivoxil to ongoing lamivudine therapy, in patients with YMDD
      variants and a reduced response to lamivudine, leads to significant inhibition of
      viral replication and improvement in liver function after 1 year of therapy.

PMID- 14688462
TI  - Recent advances of molecular targeted agents: opportunities for imaging.
AB  - A number of agents targeting components of pathways and processes critical to
      neoplastic transformation and progression are ongoing clinical development.
      Notable successes include imatinib mesylate (STI571, Gleevec) in Chronic
      Myelogenous Leukemia (CML), and Gastrointestinal Stromal Tumors (GIST) and
      trastuzumab (Herceptin) in HER2 amplified breast carcinoma. More recently,
      gefitinib (ZD1839, Iressa) and bortezomib (PS-341, Velcade) have been approved
      for refractory nonsmall cell lung carcinoma (NSCLC) and multiple myeloma (MM),
      respectively. In addition, promising results from randomized studies of
      bevacizumab (Avastin) and cetuximab (IMC-225, Erbitux) have been reported and
      shortly may lead to their approval for the treatment of colorectal carcinoma
      (CRC). To what degree the success or failure of these agents has been due to
      target, the agent, the dose or the selection of patients is uncertain. Certainly,
      further evaluation of these factors is required to optimize the therapeutic
      impact of targeted agents and imaging modalities may play a vital role in this
      process. The purpose of this review is to summarize recent results from trials of
      selected targeted agents and to suggest roles imaging may play in the further
      development of these and other targeted agents.

PMID- 14688463
TI  - Regulation of natural killer cell function.
AB  - Individuals lacking natural killer (NK) cells have persistent viral infections
      and as a consequence die prematurely. In addition, mice with decreased NK cell
      function are more susceptible to carcinogen-induced cancers. Current evidence
      strongly suggests that downregulation of MHC by certain tumors and virally
      infected cells results in NK cell attack due to the inability to trigger
      inhibitory Ly49, KIR, and NKG2A/CD94 class Ia and Ib MHC receptors. Extreme
      haplotype diversity is present in both mouse and human chromosomal segments
      coding for NK cell class Ia MHC receptors resulting in different numbers and
      types of receptors being expressed in individuals and different inbred mouse
      strains. Whether the absence or presence of a particular NK cell receptor gene is
      advantageous or deleterious for an individual with respect to immunity to
      pathogens and cancer is a question of paramount importance. Recent advances in
      our understanding of NK cell function are due to the identification of activating
      NK cell receptors, such as Ly49H and NKG2D, for specific viral and tumor ligands
      (m157 and Rae1, respectively). In a clinical setting, such MHC class I receptor
      diversity is advantageous with respect to preventing leukemic relapse in
      individuals treated for leukemia and receiving bone marrow transplants. Further
      delineation of NK cell receptors and tumor ligands will help researchers to
      exploit the innate immune system to better treat such diseases.

PMID- 14688464
TI  - Egr1 signaling in prostate cancer.
AB  - Egr1 is a multifunctional transcription factor regulating a remarkable spectrum
      of cellular responses from survival to apoptosis, growth to growth arrest,
      differentiation to transformation, senescence as well as memory and learning
      effects. In prostate cancer, Egr1 levels are constitutively high and closely
      linked to cancer development and progression. This zinc-finger protein is a short
      lived, immediate early growth response gene known to be induced by a large number
      of extracellular stimuli such as irradiation (all wavelengths tested), hypoxia,
      hyperoxia, chemotherapy agents, and more. Therefore the target genes that Egr1
      regulates in prostate cancer cells play an important role in generating many of
      the cellular responses that characterize these cells. After Egr1 binds to its
      binding sites on gene promoters, specificity of response is determined by whether
      Egr1 transcriptionally up- or downregulates the target genes. Expression
      microarray analyses combined with binding data promise new ways to identify stage
      specific cancer markers, to aid in patient risk assessment and in therapeutic
      choices.

PMID- 14688465
TI  - Targeting E3 ubiquitin ligases for cancer therapy.
AB  - E3 ubiquitin ligases are a large family of proteins that can be classified into
      three major structurally distinct types: N-end rule E3s, E3s containing the HECT
      (Homology to E6AP C-Terminus) domain, and E3s with the RING (Really Interesting
      New Gene) finger, including its derivatives, the U- Box and the PHD (Plant Homeo
      Domain). E3 ubiquitin ligases exist as single polypeptide or multimeric
      complexes. Together with ubiquitin activating enzyme E1 and ubiquitin conjugating
      enzyme E2, E3 ubiquitin ligases catalyze the ubiquitination of a variety of
      protein substrates for targeted degradation via the 26S proteasome. E3 ubiqutin
      ligases, therefore, play an essential role in regulation of many biological
      processes. Furthermore, E3s are enzymes that determine the specificity of protein
      substrates; they represent a class of "drugable" targets for pharmaceutical
      intervention. In this review, I will mainly focus on E3 ubiquitin ligases as
      potential cancer targets and discuss three of the most promising E3s, Mdm2/Hdm2,
      IAPs, and SCF, for their target rationales, target validation, and critical
      issues associated with them. These E3 ligases or their components are
      overexpressed in many human cancers and their inhibition leads to growth
      suppression or apoptosis. In addition, I will evaluate two current methodologies
      available for the high throughput screening for small molecular weight chemical
      inhibitors of the E3 ubiquitin ligases. Although targeting E3 ubiquitin ligases
      is still in its infancy, speedy approval of the general proteasome inhibitor,
      Velcade (bortezomib) by the FDA for the treatment of relapsed and refractory
      multiple myeloma suggests the promise of specific E3 inhibitors in anti-cancer
      therapy. Emerging technologies, such as siRNA, will provide a better validation
      of many E3s. It is anticipated that E3 ubiquitin ligases will represent an
      important new target platform for future mechanism-driven drug discovery.

PMID- 14688467
TI  - Role of the retinoblastoma family in gynecological cancer.
AB  - The cell cycle consists of a series of events that regulate cell life. The
      regulation and coordination result from a combination of several signals from
      different regulatory pathways which are activated in response to the presence of
      the right stimuli. Tumor suppressor genes represent a crucial milestone in the
      understanding of cancer genetics. The RB gene family includes three members:
      Rb/p105, p107 and RB2/p130. The regulation of all three members of the
      retinoblastoma family of proteins is complex and unique for each single member.
      Each member of the RB family of growth suppressive nuclear phosphoproteins
      elicits G1 growth arrest upon ectopic expression in sensitive cell lines, and
      their phosphorylation status is regulated in a cell cycle-dependent manner. In
      this review, we will discuss the role of Rb family members in the pathogenesis
      and prognosis of and their therapeutic impact on gynecological cancer.

PMID- 14688466
TI  - Mechanisms by which IGF-I may promote cancer.
AB  - Multiple large case-control studies in the past five years have reported positive
      associations between high circulating levels of the insulin-like growth factor
      (IGF)-I and risk for different types of cancer. Correlations certainly do not
      prove causation, but the reproducibility of this finding implies this is a
      hypothesis worth further examination through more mechanistic studies. IGF-I
      binds to the IGF-I receptor, a tyrosine kinase receptor that transduces signals
      to the nucleus and mitochondrion primarily via the mitogen-activated protein
      kinase (MAPK) and PI3K/Akt pathways. Examples will be provided to illustrate how
      IGF-I signaling may contribute to each stage of cancer progression: malignant
      transformation, tumor growth, local invasion and distant metastases, and
      resistance to treatment. In addition to direct contributions to each of these
      stages, IGF-I may promote cancer indirectly, through interactions with oncogenes
      and tumor suppressors, interactions with other hormones (especially the sex
      steroids in breast and prostate cancers) and interactions with the IGF binding
      proteins (IGFBPs). Finally, circulating IGF-I may facilitate cancer development
      though it likely does not cause cancer to form. Prompted by the accumulating
      evidence, investigations are also being pursued to modulate the IGF system as a
      possible means of cancer prevention or treatment.

PMID- 14688469
TI  - Radiotherapy and endothelial cells--(green) tea for two?

PMID- 14688468
TI  - Radiation induced-tubulogenesis in endothelial cells is antagonized by the
      antiangiogenic properties of green tea polyphenol (-) epigallocatechin-3-gallate.
AB  - Radiation therapy is a widely-used option for the treatment of a variety of solid
      tumors. Although effective, ionizing radiation (IR) may give rise to various side
      effects, including secondary tumors. In agreement with this, recent reports have
      demonstrated increased invasive potential in different tumor-derived cell lines
      following radiation treatment. Many of the molecular effects of IR specifically
      on the endothelial cells involved in tumor neo-vascularization remain unknown. In
      this study, we found that low sublethal single doses of IR applied to human
      umbilical vein endothelial cells stimulated cell migration and in vitro
      tubulogenesis. This correlated with an increase in membrane type-1 matrix
      metalloproteinase (MT1-MMP) protein expression, a crucial enzyme that promotes
      endothelial cell migration and tube formation, and of caveolin-1, a protein that
      regulates tube formation. Cell adhesion was also promoted by IR, reflected in
      increased gene expression levels of cell surface beta(3) integrin. Pretreatment
      of the cells with epigallocatechin-3-gallate (EGCg), a green tea catechin that
      possesses anti-angiogenic properties, prevented most of the IR-induced cellular
      and molecular events. These observations suggest that current protocols involving
      radiation therapy for the treatment of cancer can paradoxically promote
      angiogenesis, but can be improved by combination with anti-angiogenic molecules
      such as EGCg to target those tumor-derived endothelial cells that escaped IR
      induced apoptosis.

PMID- 14688470
TI  - Polymorphisms of SPINK1 N34S and CFTR in patients with sporadic and familial
      pancreatic cancer.
AB  - Long standing chronic pancreatitis is a risk factor for developing pancreatic
      cancer. Inheritance of polymorphisms in SPINK1 and CFTR are associated with an
      increased risk of developing pancreatitis. The aim of this study was to determine
      if patients who carry polymorphisms in SPINK1 and CFTR are at increased risk of
      developing pancreatic cancer through the development of chronic pancreatitis. DNA
      from patients with histologically-confirmed surgically-treated chronic
      pancreatitis, familial and sporadic pancreatic adenocarcinoma and controls were
      analyzed for the N34S polymorphism of SPINK1 and the two commonest polymorphisms
      of the CFTR gene, the DF508 mutation and the 5T polymorphism. These polymorphisms
      were determined using restriction fragment length polymorphism, PCR and cycle
      sequencing methods. The SPINK1 N34S polymorphism was detected in 5 of 172 (2.9%)
      patients with chronic pancreatitis, in 4 of 200 (2.0%) patients with sporadic
      pancreatic adenocarcinoma, in 0 of 36 (0%) of patients with familial pancreatic
      cancer and in 3 of 177 (1.7%) controls of chronic cholecystitis. The CFTR 5T
      polymorphism was identified in 31 of 334 (9.3%) patients of sporadic pancreatic
      cancer, in 5 of 43 (11.6%) patients with familial pancreatic cancer and in 10 of
      112 (8.9%) controls with colorectal cancer. The CFTR DF508 mutation was
      recognized in 6 of the 240 (2.5%) patients with pancreatic adenocarcinoma, a
      prevalence similar to that of control populations. We conclude that the N34S
      polymorphism of SPINK1 and the 5T and DF508 CFTR polymorphisms do not predispose
      to the development of pancreatic adenocarcinoma. Furthermore, the N34S
      polymorphism is rarely found in patients with severe idiopathic chronic
      pancreatitis.

PMID- 14688471
TI  - In vivo visualization of metastatic prostate cancer and quantitation of disease
      progression in immunocompromised mice.
AB  - While survival periods for patients with localized prostate cancer have
      increased, there is still no curative therapy for metastatic disease. Using non
      invasive bioluminescent imaging, we designed a comprehensive murine model to
      monitor tumor location and expansion. We detected micrometastases after one week
      that correlated by gross necropsy, autoradiography, and histopathology with organ
      and skeletal lesions seen clinically. We calculated in vivo kinetics for tumor
      growth based on biophoton emissions and observed significantly faster growth of
      bone lesions and of overall tumor burden in young mice compared to old mice. This
      model provides a controllable biological system for further investigation into
      the pathogenesis of metastatic prostate cancer and evaluation of new therapies.

PMID- 14688472
TI  - In vivo visualization of metastatic prostate cancer.

PMID- 14688473
TI  - Heat shock protein 72 does not modulate ionizing radiation-induced apoptosis in
      U1810 non-small cell lung carcinoma cells.
AB  - Heat shock proteins (HSP) have been shown to interfere with apoptosis signaling,
      suggesting that there might be a role for these proteins as mediators of
      resistance to ionizing radiation (IR)-induced apoptosis. Protein expression of
      the stress inducible heat shock proteins, HSP72 and HSP27, was analyzed in a
      panel of lung carcinoma cell lines displaying various degrees of
      radiosensitivity. Expression of HSP72 was high in all cell lines investigated
      while HSP27 was present in all non-small cell lung carcinoma (NSCLC) and 6/9
      small cell lung carcinoma (SCLC) cell lines. Heat shock, but not IR, induced or
      further increased the expression of HSP27 and HSP72. Moreover, elevation of heat
      shock protein level prior to irradiation did not attenuate IR-induced apoptotic
      signaling or the induction of apoptosis. Protein level of HSP72 was downregulated
      in a radioresistant NSCLC cell line by RNA interference. However, this did not
      sensitize cells to treatment with DNA-damaging agents such as IR, cisplatin or
      VP16. Thus, the results from this first study on the relationship between stress
      inducible HSP expression and IR-induced apoptosis in lung cancer cells do not
      support a role for HSP 27 and 72 in the radioresistance of NSCLC cells.

PMID- 14688474
TI  - Sequence dependent exposure of mammary carcinoma cells to Taxotere and the MEK1/2
      inhibitor U0126 causes enhanced cell killing in vitro.
AB  - Taxol (paclitaxel) and Taxotere (docetaxel) are considered as two of the most
      important anti-cancer chemotherapy drugs. The cytotoxic action of these drugs has
      been linked to their ability to inhibit microtubule depolymerization, causing
      growth arrest and subsequent cell death. Studies by a number of laboratories have
      also linked suppression of mitogen activated protein kinase (MAPK) signaling to
      enhanced Taxol toxicity. The present study examined the interactions of the semi
      synthetic taxane Taxotere with MEK1/2 inhibitors in epithelial tumor cells.
      Concurrent treatment of MDA-MB-231 mammary and DU145 prostate carcinoma cells
      with Taxotere and MEK1/2 inhibitor resulted in protection from the anti
      proliferative effects of Taxotere in MTT assays. In contrast, in MCF-7 mammary
      cells, concurrent Taxotere and MEK1/2 inhibitor treatment weakly enhanced the
      anti-proliferative effects of the taxane. Sequential treatment of MDA-MB-231 and
      MCF-7 cells with Taxotere followed by MEK1/2 inhibitor also enhanced the anti
      proliferative effects of the taxane in MTT assays. However, no enhancement was
      observed in DU145 or PC-3 cells. Colony formation assays, including isobologram
      analyses, provided a more definitive demonstration that MCF-7 and MDA-MB-231
      cells were sensitized to the toxic effects of Taxotere by U0126. Similar data
      were observed using Laulimalide, which binds to tubulin at a different site to
      Taxotere. The enhancement in Taxotere anti-proliferative effects by U0126
      correlated with increased cell killing, 48-72h after treatment of cells that was
      blocked by inhibition of caspase 9, but not caspase 8, function. This observation
      was associated with prolonged suppression of ERK1/2 and AKT activity, without
      alteration in either p38 or JNK1/2 activity. Collectively these findings
      demonstrate that sequential administration of Taxotere followed by MEK1/2
      inhibition can lead to increased cell death and loss of reproductive capacity in
      some, but not all, human tumor cells.

PMID- 14688475
TI  - Docetaxel cytotoxicity is enhanced by inhibition of the Raf/MEK/ERK signal
      transduction pathway.

PMID- 14688476
TI  - Haploinsufficiency of hTERT leads to telomere dysfunction and radiosensitivity in
      human cancer cells.
AB  - One of the most consistent differences between cancer cells and normal somatic
      cells is the continuous expression of telomerase, an enzyme that is important for
      maintenance of chromosome ends, or telomeres. It is believed that telomerase
      expression allows cancer cells to maintain their telomeres after many cell
      divisions and thereby avoid replicative senescence. We have tested this
      hypothesis by targeting the gene encoding the catalytic subunit of the telomerase
      holoenzyme, hTERT, in a human cancer cell line. Heterozygous disruption of hTERT
      led to a reduction in telomerase activity, telomere shortening, activation of DNA
      damage signaling and the appearance of a subpopulation of cells that displayed
      features of senescence. Targeted cells were radiosensitive, as compared with
      parental controls that had two intact hTERT alleles, and expressed a classical
      marker of senescence after irradiation. These results suggest that telomerase
      inhibitors might be useful in the sensitization of cancer cells to DNA damaging
      agents.

PMID- 14688477
TI  - Telomerase expression--only half the story.

PMID- 14688478
TI  - An essential role of Th1 responses and interferon gamma in infection-mediated
      suppression of neoplastic growth.
AB  - We had previously demonstrated that in mice acute toxoplasmosis leads to systemic
      inhibition of angiogenesis and, consequently, strong suppression of neoplastic
      growth. Here we investigated the role of Th1 cytokines, in particular interferon
      gamma (IFN-gamma), in this phenomenon. Besides toxoplasma, neoplastic growth was
      readily blocked during acute infection with other Th1 response-inducing pathogens
      such as Listeria monocytogenes and lymphocytic choriomeningitis virus (LCMV). In
      contrast, chronic infection with LCMV (when Th1 responses were strongly
      suppressed) and acute infection with Schistosoma mansoni (when Th2 responses
      predominated) afforded no anti-tumor protection. To corroborate the involvement
      of Th1 cytokines in infection-mediated suppression of neoplastic growth, we
      utilized mice deficient in interleukin-10 (IL10), a suppressor of Th1 responses.
      When challenged with B16 cells concomitantly with toxoplasma infection, both IL10
      null and wild type mice exhibited resistance to neoplastic growth. However,
      tumors borne by IL10-null animals were even smaller than those borne by their
      wild type counterparts. This enhanced resistance correlated with dramatically
      elevated levels of circulating IFN-gamma, a principal Th1 cytokine. Furthermore,
      while interleukin-12 and tumor necrosis factor a were dispensable for tumor
      suppression, in animals deficient in IFN-gamma production or signaling, tumor
      growth and neovascularization were markedly enhanced. Interestingly, the
      enhancement was also apparent in uninfected animals suggesting that IFN-gamma and
      its anti-angiogenic effects underlie both infection-dependent and -independent
      tumor surveillance.

PMID- 14688479
TI  - Differential apoptotic response to the proteasome inhibitor Bortezomib [VELCADE,
      PS-341] in Bax-deficient and p21-deficient colon cancer cells.
AB  - Targeting the ubiquitin-proteasome pathway has emerged as a promising approach
      for treating cancer. Bortezomib (VELCADE, formerly known as PS-341), a potent and
      reversible proteasome inhibitor, is being evaluated in clinical trials for
      treating multiple myeloma, and various other types of hematologic and solid
      tumors. Proteasome inhibitors are known to induce apoptosis in human cancer
      cells. Nevertheless, the mechanisms of apoptosis induced by proteasome inhibitors
      remain unclear. In this study, we investigated the role of p53 and its downstream
      targets in bortezomib-induced apoptosis in HCT116 human colon cancer cells. We
      demonstrated that bortezomib induced p53, and activated its downstream genes p21,
      PUMA and Bax in a p53-dependent fashion. However, apoptotic response to
      bortezomib was not affected by the deletion of p53. Surprisingly, we found that
      bortezomib-induced apoptosis was markedly enhanced in the p21-knockout cells,
      while significantly decreased in the BAX-knockout cells. Furthermore, in the
      cells deficient for both Bax and p21, apoptosis was restored to the level in the
      parental or the p53-deficient cells. The opposite effects of Bax and p21 were
      unrelated to the extent of proteasome inhibition, and were also observed in cells
      treated with different proteasome inhibitors. These results indicate that p53
      downstream targets can collectively modulate apoptotic response to bortezomib and
      other proteasome inhibitors.

PMID- 14688480
TI  - Human somatic cell knockouts reveal determinants of sensitivity and resistance to
      proteasome inhibitor PS-341.

PMID- 14688482
TI  - Caspase 10 levels are increased following DNA damage in a p53-dependent manner.
AB  - p53 plays a central role in the cellular response to stressful stimuli, including
      DNA damage, aberrant growth signals, and hypoxia. Upon activation, it binds to a
      specific DNA binding motif and functions to transcriptionally activate or repress
      different groups of genes. The biologic outcome of these events can lead to cell
      cycle arrest, DNA repair, or apoptosis. While many downstream targets of p53 have
      been identified, the factors that determine which of these outcomes will occur in
      an individual cell are less clear. In this study, we show that caspase 10, an
      initiator caspase, is induced in response to DNA damaging chemotherapeutic agents
      in a p53-dependent manner. Following treatment with etoposide or adriamycin,
      induction of caspase 10 occurred at both the mRNA and protein levels. In
      contrast, DNA damage did not affect levels of caspase 8, another initiator
      caspase with significant structural and functional homology to caspase 10. By
      chromatin immunoprecipitation assay, p53 bound in vivo to multiple p53-specific
      binding sites located within the caspase 10 gene locus, suggesting that caspase
      10 is a direct transcriptional target of p53. Upregulation of caspase 10 may
      represent one factor that determines how p53 activation leads to cellular
      apoptosis following DNA damage.

PMID- 14688481
TI  - MUC1 cytoplasmic domain coactivates Wnt target gene transcription and confers
      transformation.
AB  - The DF3/MUC1 mucin-like transmembrane oncoprotein is overexpressed by most human
      carcinomas. The MUC1 cytoplasmic domain (CD) binds directly to the Wnt effector,
      beta-catenin, and colocalizes with beta-catenin in the nucleus; however, the
      nuclear function of MUC1 is unknown. The present results demonstrate that MUC1
      coactivates transcription of beta-catenin-Tcf-binding sites in the pTOPFLASH
      reporter. Activation of transcription was abrogated by expression of MUC1 with a
      Y-46->F mutation in the CD that attenuates binding of MUC1 and beta-catenin. We
      also show that transcription of the Wnt responsive cyclin D1 promoter is
      activated by MUC1, but not MUC1(Y46F), and that the cyclin D1 gene is upregulated
      in MUC1-positive cells. In concert with these results, MUC1-induced anchorage
      independent growth and tumorigenicity were also abrogated by mutating MUC1 at the
      Y-46 site. These findings support a model in which the MUC1 functions as a
      transforming protein by coactivating transcription of Wnt target genes.

PMID- 14688483
TI  - Analysis of cyclooxygenase 2 (COX-2) expression during malignant melanoma
      progression.
AB  - Cyclooxygenase 2 (COX-2) is an inducible enzyme involved in the production of
      prostaglandins and thromboxanes during inflammation. There are now several lines
      of evidence indicating that increased expression of COX-2 plays a functional role
      in the development and progression of malignant epithelial cancers. However,
      there is only limited data regarding the role of COX-2 in melanoma pathogenesis.
      In the present work, we retrospectively examined lesions through out the
      development of melanoma and metastatic disease (dysplastic nevi n = 10, melanoma
      in situ n = 4, stage II melanoma n = 10, stage III n = 4, stage IV n = 3, stage V
      n = 2, melanoma metastasis lymph nodes n = 13 metastasis to other sites n = 3).
      COX-2 was consistently observed in keratinocytes, dermal fibroblasts, and
      inflammatory cells in regions adjacent to benign evi and primary cutaneous
      melanomas. However, no COX-2 staining was detected in the nevi nor in the primary
      skin melanoma cells. In addition, COX-2 was undetected in all vertical and radial
      growth phase cases Interestingly, 13 out of 13 of the lymph node metastasis
      expressed extremely high levels of COX-2 in overlying epithelium and inflammatory
      cells, and COX-2 was strongly detected in the metastatic cancer cells per se. For
      additional information on the expression of COX-2 in malignant melanoma, we
      determined the expression of COX-2 protein in several different melanoma cell
      lines. We found that 3We found that 5 out of 7 of the melanoma cells over
      expressed COX-2 compared to normal melanocytes. Collectively, these data suggest
      that COX-2 may play a functional role in metastases of melanoma, and treatment
      with COX-2 inhibitors may be efficacious for malignant melanoma.

PMID- 14688484
TI  - A passion for discovery.

PMID- 14688485
TI  - First international melanoma research congress.

PMID- 14688488
TI  - Hypertension in the metabolic syndrome and diabetes: pathogenesis, clinical
      studies, and treatment.
AB  - The increasing prevalence of obesity, hypertension, and abnormal glucose
      metabolism is a major challenge to health care in industrialized societies. This
      brief review summarizes the mechanistic evidence and clinical studies related to
      the problem of hypertension in the metabolic syndrome and diabetes to allow
      clinicians to provide more effective and enlightened management of these common,
      interrelated problems.

PMID- 14688489
TI  - Management of older hypertensive patients: is there a difference in approach?
AB  - Hypertension is the most common reason Americans visit a physician. Recent
      analyses from the Framingham Heart Study and others have shown that there will be
      70 million hypertensive Americans by the year 2020 and that the overwhelming
      majority of hypertensives will be 65 years of age or older (what we used to call
      elderly). The lifetime risk of Americans who live to age 85 years of becoming
      hypertensive is approximately 90% for both men and women. These individuals, even
      if they develop an elevated blood pressure late in life, are at significantly
      increased risk of the many medical complications attributable to hypertension
      (coronary artery disease, strokes, heart failure, chronic renal disease, and
      more). Older hypertensives are more likely to have an elevated systolic blood
      pressure and a low diastolic blood pressure, both of which are related to a loss
      of article compliance and have an increase in left ventricular mass and a
      decrease in peripheral resistance. We now have a substantial body of evidence
      from well done clinical trials that older hypertensives benefit as much or more
      than younger patients from antihypertensive therapy, so there is no longer any
      justification for withholding medication from any hypertensive patient whose
      competing risk or other medical problems are not a contraindication to treatment.
      These same studies, and practice-based analyses, have shown that the major
      barrier to reaching blood pressure goal is our failure to reduce systolic blood
      pressure to <140 mm Hg in most patients and to <130 mm Hg in diabetics and those
      with renal failure. The basis for all antihypertensive therapy, especially in
      older people, is thiazide diuretics with either angiotensin-converting enzyme
      inhibitors, angiotensin receptor blockers, beta blockers, or calcium entry
      blockers as appropriate add-on treatment. The choice of the second agent depends
      on other factors, such as comorbidity, lifestyle, and affordability. We must be
      more aggressive in getting the message out that older hypertensives benefit from
      treatment and we must overcome the clinical inertia that seems to be a factor in
      the decision of many physicians not to treat an older patient. No older person
      should suffer a preventable, life-threatening event or become confined to a wheel
      chair if attention to lifestyle issues and a few pills a day could avoid that
      outcome.

PMID- 14688490
TI  - Rationale for combination therapy in the management of hypertension.
AB  - Combination drug therapy in the management of hypertension has been used for many
      years. Recent recommendations of the Seventh Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and the
      results of several new multiple-drug trials have focused on using the approach as
      initial therapy in many hypertensive patients. Results of these long-term outcome
      trials, as well as short-term and smaller studies, indicate the advantage of
      multiple-drug therapy in the management of hypertension.

PMID- 14688491
TI  - Plasma renin measurement in the management of hypertension: the V and R
      hypothesis.

PMID- 14688492
TI  - Characteristics and lipid distribution of a large, high-risk, hypertensive
      population: the lipid-lowering component of the Antihypertensive and Lipid
      Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
AB  - The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
      (ALLHAT) consisted of 42,418 participants randomized to one of four
      antihypertensive treatment groups: chlorthalidone, amlodipine, lisinopril, or
      doxazosin. A subset of these participants with fasting low-density lipoprotein
      cholesterol levels 100-189 mg/dL were randomized into a lipid-lowering component:
      5170 to receive pravastatin (40 mg daily) and 5185 to receive usual care. This
      report describes the characteristics and lipid distribution of these
      participants. There were no important differences between the randomized
      treatment groups. Women had higher total cholesterol, low-density lipoprotein
      cholesterol, and high-density lipoprotein cholesterol than men. There was a
      similar finding for black participants compared with whites, except blacks had
      lower triglycerides. Diabetics had lower high-density lipoprotein cholesterol and
      higher triglycerides than nondiabetics, and patients with body mass index <25
      kg/m(2) had higher high-density lipoprotein cholesterol but lower low-density
      lipoprotein cholesterol and triglycerides than patients with higher body mass
      index. The success of the randomization of this large, diverse population and the
      differences in the lipid distributions among its subgroups will allow further
      understanding of optimal lipid-lowering treatment.

PMID- 14688493
TI  - Physician-nurse team approaches to improve blood pressure control.
AB  - Hypertension is an asymptomatic chronic disease that contributes to the
      development of serious health problems including coronary artery disease, chronic
      renal failure, and stroke. Despite published guidelines addressing goals for the
      treatment of hypertension, control rates (defined as a blood pressure <140/90 mm
      Hg) have not increased in recent years, and uncontrolled hypertension remains a
      serious public health issue. Both patient- and provider-related factors
      contribute to these poor control rates, and new approaches to the management of
      hypertension must be sought. In this review, we describe unique physician-nurse
      team approaches to improve the control of hypertension both in a subspecialty
      hypertension practice and in a primary care clinic setting. By implementing
      practice models that result in sustainable improvements in blood pressure control
      rates, the morbidity and mortality resulting from target organ damage and ensuing
      costs to society may be expected to decline as well.

PMID- 14688495
TI  - Roundtable discussion: Electrolytes in cardiovascular disease and hypertension.

PMID- 14688494
TI  - Meeting the challenge to improve the treatment of hypertension in blacks.
AB  - Hypertension is more prevalent and severe in African descendent populations
      living outside Africa than in any other population. Given this greater burden of
      hypertension in blacks, it is increasingly necessary to refine strategies to
      prevent the disorder as well as improve its treatment and control. This review
      assesses results from clinical trials on lifestyle and pharmacologic
      interventions to identify which approaches most effectively prevent adverse
      hypertension-related outcomes in African descendent populations. The Dietary
      Approaches to Stop Hypertension (DASH) study provided evidence that a carefully
      controlled diet rich in fruits, vegetables, low-fat dairy foods, and reduced in
      saturated fat, total fat, and cholesterol (i.e., the DASH diet) reduces blood
      pressure in blacks and is well accepted. The combination of the DASH diet with
      reduction in dietary sodium below 100 mmol/d may provide a reduction in blood
      pressure beyond that reached by the DASH diet alone. Physical exercise and
      interventions to reduce psychological stress may also reduce blood pressure in
      blacks. Strong evidence from numerous studies is a compelling argument for
      continuing to recommend diuretics and beta blockers as first-line
      antihypertensive therapy for persons of all races. Some new studies also favor
      angiotensin-converting enzyme inhibitors as first-line antihypertensive drugs.
      The African American Study of Kidney Disease and Hypertension provided evidence
      that an angiotensin-converting enzyme inhibitor-based treatment program is more
      beneficial than calcium channel blockers and beta blockers in reducing the
      progression of renal failure in blacks with hypertensive nephropathy. Studies in
      patients with diabetes have also shown evidence that both angiotensin-converting
      enzyme inhibitors and angiotensin receptor antagonists are more effective than
      other classes of antihypertensives in reducing adverse renal events. Studies to
      evaluate the effects of the new antihypertensives in improving outcomes in blacks
      living outside the United States are needed.

PMID- 14688497
TI  - Isolated diastolic hypertension.

PMID- 14688498
TI  - Combination angiotensin-converting enzyme inhibitor and angiotensin receptor
      blocker therapy: its role in clinical practice.
AB  - Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are
      commonly prescribed for the management of hypertension. In addition, each of
      these drug classes has been shown to be effective in the treatment of congestive
      heart failure, proteinuric chronic kidney disease, and most recently the high
      cardiac-risk profile patient. The individual success of each of these drug
      classes has fueled the theory that given together, the overall biologic effect of
      both would surpass that of either given alone. The foundation of this premise,
      although biologically plausible, has yet to be proven in a compelling enough
      fashion to support the everyday use of these two drug classes in combination.
      Additional clarifying studies are required to establish whether specific patient
      subsets exist that might benefit from such combination therapy.

PMID- 14688499
TI  - Is funduscopy clinically useful in the evaluation of the hypertensive patient?

PMID- 14688500
TI  - Amlodipine and losartan: reaction to comparison.

PMID- 14688501
TI  - Safety and efficacy of therapeutically equivalent doses of sustained-release
      formulations of isradipine and felodipine.
AB  - This open-label, drug substitution study was conducted to determine if subjects
      receiving sustained-release isradipine (SR-I) can be safely switched to sustained
      release felodipine (SR-F) and to assess whether SR-I provides better 24-hour
      blood pressure (BP) control than SR-F. Forty-one men receiving either SR-F 5 mg
      or SR-F 10 mg once daily for at least 6 months were switched to an equivalent
      dose of SR-I; BP was measured 2, 4, and 6 weeks after substitution. Significant
      reductions in systolic BP were seen in the SR-I 10 mg group after 4 weeks and
      they remained significantly lower through 6 weeks (p< or =0.05). Diastolic BP was
      reduced, but not significantly. After 6 weeks, SR-F therapy was reinstated, and
      BP returned toward baseline values. No serious adverse events were reported. SR-I
      can be safely substituted for SR-F and may provide better 24-hour control of BP
      than SR-F.

PMID- 14688502
TI  - Retrospective review: the incidence of non-ST segment elevation MI in emergency
      department patients presenting with decompensated heart failure.
AB  - The authors performed a 6-month review of heart failure patients presenting to a
      teaching hospital emergency department to determine the rate of positive serum
      myocardial infarction markers. All patients with an emergency department
      discharge diagnosis of heart failure were included; those with a creatinine level
      >2.0 mg/dL were excluded. There were 151 patients who met the entry criteria,
      with a mean age of 68.6 +/- 13.6 years, and 84 (56%) were men. The mean ejection
      fraction was 32%, and the mean Framingham score was 3.8 +/- 1.6. Twenty (14%) had
      positive markers. Troponin T was positive in 17 (11%), and creatine kinase was
      positive in nine (6%). Both markers were positive in six (4%). Chest pain was
      absent in 70% of the positive marker group. The authors conclude that elevated
      cardiac markers are not rare in decompensated heart failure. These pilot data
      suggest these tests should be routinely obtained on heart failure patients.

PMID- 14688504
TI  - Heart failure in the elderly.
AB  - Incidence and prevalence of heart failure are particularly common with advancing
      age, with notoriously grim prognoses. The absolute number of heart failure
      patients will undoubtedly surge as the population of older adults continues to
      escalate. This review emphasizes the importance of factors inherent in aging
      itself and the resulting predisposition to disease. Physiologic changes
      associated with cardiovascular aging fundamentally increase susceptibility to
      heart failure and to complexity of heart failure management. Likewise, typical
      age-associated diet and lifestyle changes compound risks of heart failure through
      mechanisms connected to the substrate of disease. In this review, the authors
      first summarize the demographics of heart failure and the intrinsic aspects of
      aging and lifestyle that predispose to heart failure. They then expand on related
      intricacies of diagnosis and therapy. Orientation to heart failure, particularly
      as a disease of aging, can help critically refine management of acute and chronic
      disease, as well as foster preventive strategies to reduce incidence of this
      common malady.

PMID- 14688505
TI  - Adherence to antihypertensive therapy with fixed-dose amlodipine
      besylate/benazepril HCl versus comparable component-based therapy.
AB  - Adhering to medication regimens has the potential to significantly improve
      clinical outcomes for persons with high blood pressure. A patient-related factor
      likely to affect adherence to treatment is the convenience of the prescribed drug
      regimen. The authors hypothesized that medication adherence would be superior and
      cost benefits would accrue in subjects who receive a once-daily, single-capsule,
      fixed-dose combination product for blood pressure control, compared with subjects
      who receive a similar regimen of separate components. A managed care organization
      that provides benefits for members enrolled in various health plans provided the
      data for this retrospective analysis. The database was used to assess medication
      adherence patterns for two groups of hypertensive subjects. Group 1 included
      subjects who had been prescribed the single-capsule, fixed-dose combination of
      amlodipine besylate/benazepril HCl. Group 2 comprised subjects who had been
      prescribed a regimen including an angiotensin-converting enzyme inhibitor and a
      dihydropyridine calcium channel blocker as separate drugs. Adherence was measured
      by the medication possession ratio, and medical resource utilization by the two
      groups was assessed during the study period. Group 1 (n=2754) and Group 2
      (n=2978) were balanced with regard to age (mean, 53 years; range, 18-64 years)
      and sex (men, 50%; women, 50%). The overall medication possession ratio for Group
      1 was significantly higher than that for Group 2 (80.8% vs. 73.8%; p<0.001). The
      average annual cost of cardiovascular-related care per subject was significantly
      lower in Group 1 compared with Group 2 (p<0.001). Subjects receiving the once
      daily, single-capsule, fixed-dose combination of amlodipine/benazepril HCl
      demonstrated significantly better medication adherence and required fewer medical
      resources than did subjects receiving an angiotensin-converting enzyme inhibitor
      and a dihydropyridine calcium channel blocker as separate components.

PMID- 14688506
TI  - Prevalence, prognostic significance, and treatment of atrial fibrillation in
      congestive heart failure with particular reference to the DIAMOND-CHF study.
AB  - Atrial fibrillation is a growing health problem and the most common cardiac
      arrhythmia, affecting 5% of persons above the age of 65 years. The number of
      hospital discharges for atrial fibrillation has more than doubled in the past
      decade. It occurs very often in patients with congestive heart failure and the
      prevalence increases with the severity of the disease. These two conditions seem
      to be linked together, and congestive heart failure may either be the cause or
      the consequence of atrial fibrillation. The prognosis of atrial fibrillation is
      controversial, but studies indicate that atrial fibrillation is a risk factor in
      congestive heart failure patients. In the last 10-15 years, significant advances
      in the treatment of heart failure have improved survival, whereas effective
      management of atrial fibrillation in heart failure patients still awaits similar
      progress. Empirically, two strategies have evolved for treatment of atrial
      fibrillation: 1) rhythm control, which means conversion to sinus rhythm and
      maintenance of sinus rhythm; and 2) rate control, which means reduction of heart
      rate to an acceptable frequency. It is unknown whether one of these strategies is
      better than the other. In this review the authors discuss the prevalence, impact,
      and treatment of atrial fibrillation in heart failure patients.

PMID- 14688507
TI  - New therapy update. Inspra (eplerenone tablets).

PMID- 14688508
TI  - Difficult cases in heart failure. Percutaneous transluminal septal myocardial
      ablation in the management of hypertrophic obstructive cardiomyopathy.
AB  - Hypertrophic cardiomyopathy is a complex genetic condition with a heterogeneous
      clinical course. Some patients remain asymptomatic throughout life while others
      develop one or more of the adverse clinical consequences including symptoms of
      congestive heart failure with exertional dyspnea and functional disability
      (usually with preserved left ventricular systolic function), atrial fibrillation,
      or sudden cardiac death. Because of this heterogenicity in the clinical
      presentations, management of patients with hypertrophic cardiomyopathy includes a
      wide range of pharmacologic therapies as well as invasive approaches. In recent
      years, nonsurgical catheter-based treatment of hypertrophic cardiomyopathy has
      been increasingly used in the management of a subset of these patients. The
      authors present a case of percutaneous transluminal septal myocardial ablation in
      a patient with hypertrophic cardiomyopathy who was symptomatic despite maximal
      medical treatment.

PMID- 14688511
TI  - Interfacing dendritic and natural killer cells: a tool for targeted tolerance
      induction?

PMID- 14688512
TI  - Donor-specific tolerance in fully major histocompatibility major
      histocompatibility complex-mismatched limb allograft transplants under an anti
      alphabeta T-cell receptor monoclonal antibody and cyclosporine A protocol.
AB  - BACKGROUND: Recent studies have demonstrated that treatment with alphabeta-T-cell
      receptor (TCR) monoclonal antibody and cyclosporine A (CsA) can extend survival
      in composite tissue allografts (CTA). The purpose of this study was to induce
      tolerance in fully major histocompatibility complex (MHC)-mismatched rat limb
      allografts under 7 days of a combined alphabeta-TCR-CsA protocol. METHODS: The
      authors performed 30 hind-limb allotransplantations across the MHC barrier
      between Brown Norway donors (BN; RT1n) and Lewis recipients (LEW; RT1l). Isograft
      and allograft controls received no treatment. The experimental groups received
      monotherapy of alphabeta-TCR and CsA or a combination of alphabeta-TCR and CsA
      for 7 days only. Donor-specific tolerance and immunocompetence were determined by
      standard skin grafting in vivo and mixed lymphocyte reaction (MLR) in vitro. The
      efficacy of immunosuppressive therapy and the level of donor-specific chimerism
      were determined by flow cytometry. RESULTS: Long-term survival (>350 days) was
      achieved in allograft recipients (n=6) under the 7-day protocol of combined
      alphabeta-TCR-CsA. Donor-specific tolerance and immunocompetence of long-term
      chimeras were confirmed by acceptance of skin grafts from the donors and
      rejection of the third-party alloantigens (AxC Irish). At day 120, MLR
      demonstrated unresponsiveness to the host and donor antigens but strong
      reactivity against third-party alloantigens. Flow cytometry confirmed the high
      efficacy of immunosuppressive treatment and the development of donor-specific
      chimerism (7.6% of CD4+-RT1n+ cells, 1.3% of CD8+-RT1n+ cells, and 16.5% of
      CD45RA+-RT1n+ cells) in the periphery of tolerated recipients. CONCLUSIONS:
      Combined therapy of alphabeta-TCR-CsA for 7 days resulted in tolerance induction
      in fully MHC-mismatched rat hind-limb allografts. Tolerance was directly
      associated with stable, donor-specific chimerism.

PMID- 14688513
TI  - The effect of simultaneous CD154 and LFA-1 blockade on the survival of allogeneic
      islet grafts in nonobese diabetic mice.
AB  - BACKGROUND: The rate of success in clinical transplantation of islets of
      Langerhans has dramatically improved with perspectives of wide-scale
      applicability for patients with type 1 diabetes. One drawback is the need for
      lifelong immunosuppression, which is associated with significant side effects.
      Immunomodulatory strategies devoid of side effects and with tolerogenic
      potential, such as co-stimulatory blockade, would be a great improvement if
      successful. In this study, the authors have explored the effect of simultaneous
      blockade of CD40/CD154 and intercellular adhesion molecule (ICAM)/lymphocyte
      function-associated antigen (LFA)-1 interactions. METHODS: Spontaneously diabetic
      nonobese diabetic (NOD) mice underwent transplantation with allogeneic (C57BL/6)
      islets and were treated with anti-CD154 monoclonal antibody (mAb) (500 microg,
      three doses), anti-LFA-1 mAb (100 microg, three doses), or a combination of both
      in the early peritransplant period. In another set of experiments, LFA-1
      engagement was impaired by transplanting islets isolated from ICAM-1-knockout
      (KO) mice. RESULTS: Untreated animals rejected their grafts within 10 days. LFA-1
      blockade alone did not result in improved islet graft survival, whereas CD154
      blockade alone increased graft survival to 18 days. Simultaneous blockade of both
      pathways led to significantly improved islet graft survival to 30 days (ICAM-1-KO
      islets plus anti-CD154), 35 days (anti-LFA-1 plus anti-CD154), and 44 days (ICAM
      1-KO islets plus anti-LFA-1 plus anti-CD154). CONCLUSIONS: These data suggest
      that a synergistic effect for prolonged graft survival can be obtained by
      simultaneously targeting CD154 and LFA-1 in the challenging model of islet
      allotransplantation in NOD mice. The observation of similar results with anti-LFA
      1 mAb and with ICAM-1-KO grafts suggests a key role of direct antigen
      presentation for the activation of LFA-1-driven signaling.

PMID- 14688514
TI  - Cell-mediated cytotoxicity to porcine aortic endothelial cells is not dependent
      on galactosyl residues when baboon peripheral blood lymphocytes are previously
      primed with pig xenoantigens.
AB  - BACKGROUND: In the pig-to-baboon model, acute vascular rejection remains the main
      hurdle for successful long-term xenograft survival. The production of galactosyl
      knockout pigs could solve concomitantly the problem of hyperacute and acute
      vascular rejection. This work studies in vitro the cell-mediated cytotoxicity of
      natural killer (NK) and T cells after priming of baboon peripheral blood
      lymphocytes (PBLs) with pig antigens to evaluate whether cytotoxicity is
      galactosyl-dependent. MATERIAL AND METHODS: PBLs from naive and primed baboons
      were used as effectors on primary porcine aortic endothelial cells (PAECs) to
      assess cytotoxicity. Untreated or galactosidase-digested PAECs were used to
      evidence the role of galactosyl residues on cell-mediated cytotoxicity. Two rat
      anti baboon monoclonal antibodies were tested to inhibit either T+NK cells (LO
      CD2b) or NK cells alone (LO-CD94). RESULTS: When using PBLs from naive animals,
      spontaneous lysis occurred and was inhibited by both LOCD-2b and LO-CD94. In
      comparison, lysis of PAECs was significantly higher when baboon PBLs were first
      primed in vivo with pig xenoantigens. In this case, cytotoxicity was completely
      inhibited by LO-CD2b but only partially by LO-CD94. Reduction of galactosyl
      residues by galactosidase digestion showed that PAEC lysis almost completely
      disappeared with naive baboon PBLs but not with primed baboon PBLs, thereby
      indicating that anti-pig T-cell response is not dependent on galactosyl residues.
      CONCLUSION: Galactosyl knockout pigs could solve hyperacute rejection and also
      prevent the activation of NK cells even after xenogeneic priming. T cells will
      then be the next hurdle for the success of xenografting.

PMID- 14688515
TI  - L-carnitine ameliorates abnormal vulnerability of steatotic rat livers to cold
      ischemic preservation.
AB  - BACKGROUND: Up to 30% of all livers retrieved for organ transplantation exhibit
      steatotic transformations. Chronic organ-donor shortage has led to the acceptance
      of these organs for transplantation, although a higher risk of graft nonfunction
      is associated with the preservation of steatotic livers. METHODS: A dietary
      steatosis was induced in Wistar rats by fasting them for 2 days and feeding them
      with a fat-free diet. Fatty livers (n=14) were retrieved and flushed with 60 mL
      of histidine, tryptophane, alpha-ketoglutarate (HTK) solution. In half of the
      experiments, L-carnitine (5 mM) was added to the HTK. Functional integrity of the
      livers was evaluated by isolated reperfusion with KHB in a recirculating system
      at 37 degrees C for 45 minutes. RESULTS: Addition of L-carnitine to the HTK
      promoted a significant reduction of the enzyme leakage from the livers upon
      reperfusion. Release of alanine-aminotransferase was reduced to one third (127+/
      22 vs. 423+/-61 U/L), and the loss of glutamate dehydrogenase in the perfusate
      could be reduced significantly (42+/-7 vs. 542+/-134 U/L) when compared with
      livers stored without additional medication. Morphologic corroboration of these
      data was obtained by electron microscopy. Although normal appearance of liver
      mitochondria was preserved at the end of the cold ischemic storage, reperfusion
      of cold-stored fatty livers entailed massive alterations and frequent destruction
      of hepatic mitochondria. However, these morphologic impairments were remarkably
      mitigated in the carnitine-treated group. CONCLUSIONS: L-carnitine represents a
      feasible metabolic adjunct for a safe and more successful preservation of
      ischemia-reperfusion-sensitive steatotic livers.

PMID- 14688517
TI  - Prothrombotic disorders in uremic type-1 diabetics undergoing simultaneous
      pancreas and kidney transplantation.
AB  - BACKGROUND: Although prothrombotic disorders (PTD) are known to increase the risk
      of graft failure in kidney transplantation only, there are no data on PTD in
      simultaneous pancreas and kidney transplantation (SPK). METHODS: Forty-seven SPK
      performed between September 2000 and July 2002 underwent routine screening for
      PTD. Data were retrospectively analyzed in view of complications (relaparotomy,
      graft thrombosis, pancreatitis, rejection) and graft function (HbA1c, serum
      creatinine) 3 months posttransplantation. RESULTS: Twenty-five of forty-seven
      (53.2%) patients had 30 PTDs. Homozygous mutations of the MTHFR gene (C677T) were
      found in six, factor-V Leiden mutation (homo- or heterozygous G1691A) in seven,
      and prothrombin mutation (20210A) in one patient (group 1). Group 2 consists of
      deficiencies of protein C (n=1), of protein S (n=12), of antithrombin (n=1), and
      antiphospholipid syndromes (n=2). Overall, PTD had no influence on graft
      thrombosis (P=0.36) or rejection (P=0.56). In patients with homozygous mutations,
      relaparotomies were more often necessary than in patients without mutations
      (42.9% vs. 11.8%, P=0.046). In group 1, there was a trend toward a higher
      incidence of graft pancreatitis than in patients without mutations (38.5% vs.
      14.7%, P=0.075). Three months posttransplantation, HbA1c was 6.0% in patients
      with and 5.5% in patients without PTD (P=0.023). With regard to serum creatinine,
      no significant differences were observed. CONCLUSION: PTD are frequent in type-1
      diabetics receiving SPK and may have a role in relaparotomies, graft
      pancreatitis, and pancreas graft function.

PMID- 14688516
TI  - Three-year posttransplant graft survival in renal-transplant patients with graft
      function at 6 months receiving tacrolimus or cyclosporine microemulsion within a
      triple-drug regimen.
AB  - BACKGROUND: Registry data can provide valuable information about possible
      treatment effects; however, pretreatment differences in patient characteristics
      may influence treatment assignment. Careful analysis must therefore be undertaken
      when evaluating treatment differences in the context of nonrandomized studies so
      that the impact of treatment selection bias is minimized. METHODS: A
      multivariable risk factor analysis of adult patients registered in the US Renal
      Data System who received a primary renal allograft during 1995 to 1998 was
      undertaken to compare 3-year graft survival using tacrolimus or Neoral with
      mycophenolate mofetil (MMF) and steroids. RESULTS: In total, 9,449 patients were
      included (cadaveric donor n=6,011; living donor n=3,438). Patients (2,130)
      received tacrolimus, and 7,319 received Neoral. At 3 years posttransplant, the
      proportion of cadaveric donor recipients experiencing all causes of graft loss
      was 10.0% for tacrolimus and 10.6% for Neoral; for living donor recipients these
      figures were 6.5% and 6.7%, respectively (unadjusted Kaplan-Meier analysis). The
      incidence of graft failure excluding death was also similar between the two
      groups. With Cox proportional hazards modeling, the adjusted relative hazard of 3
      year graft failure for cadaveric donor patients taking tacrolimus versus Neoral
      was 1.02 (95% confidence interval [CI] 0.8-1.3), and for living-donor recipients
      it was 1.15 (95% CI 0.8-1.8). CONCLUSIONS: These results indicate excellent 3
      year graft survival for both cadaveric and living-donor renal-transplant patients
      receiving either Neoral or tacrolimus with MMF and steroids, with no significant
      differences between treatment groups. On the basis of these results, relative
      cost-effectiveness may become increasingly important in selection of tacrolimus
      or Neoral as primary immunosuppressant for renal-transplant patients.

PMID- 14688518
TI  - A multiorgan donor cancer screening protocol: the Italian Emilia-Romagna region
      experience.
AB  - BACKGROUND: We describe the Emilia-Romagna screening protocol for all multiorgan
      donors within this region of Italy and report on the first 2 years of
      implementation. SETTING: Setting is a 24-hour multidisciplinary call service
      covering the 16 intensive care units in Emilia-Romagna (3,969,000 inhabitants)
      and a centralised pathology center, directed by a transplant coordination center.
      STUDY POPULATION AND PERIOD: All 271 effective donor candidates presenting in
      Emilia-Romagna in 2001-2002. PROTOCOL: Anamnesis, external examination, and
      thorough laboratory and instrumental screening is followed by sampling of
      internal effusions and evaluation of all internal organs. All suspect findings
      are then investigated by extemporary pathologic evaluation. To fit national legal
      requirements, candidates are classified as standard risk (no transmissible risk);
      nonstandard risk (low-risk of transmission, eligibility restricted to certified
      clinical emergencies pending informed consent); and unacceptable risk
      (unconditional exclusion because of high-risk pathologies). RESULTS: The protocol
      was successfully implemented for all 271 candidates. In addition to 14
      independent exclusions, clinical suspicion of cancer was raised for 61 donors
      presenting with 82 lesions or effusions. Along with one case of lymph-node
      tuberculosis (unacceptable risk), histocytologic screening revealed eight cases
      of malignancy (5 prostate, 1 papillary-thyroid, 1 follicular-thyroid, and 1 renal
      cell, all nonstandard risk); the remainder were benign (standard risk). Protocol
      implementation led to exclusion of 8 (3.0%) candidates (1 nonstandard risk
      transplantation was performed). CONCLUSIONS: This stringent protocol-now adopted
      with some modifications at a national level-provides an initial example of a
      feasible intervention aimed at maximising donation safety while rationalizing use
      of marginal donors.

PMID- 14688519
TI  - Quality of life in adult survivors beyond 10 years after liver, kidney, and heart
      transplantation.
AB  - BACKGROUND: The yearly increasing survival rates testify to the success of
      transplantation, but questions remain relating to the quality of life (QOL)
      associated with long-term survival. METHODS: A sample of 126 liver recipients
      (Liver-R), 229 kidney recipients (Kidney-R), and 113 heart recipients (Heart-R)
      with more than 10 years posttransplant follow-up were included in the study with
      a response rate of 86%. Respondents were matched with healthy subjects recruited
      from general population (GP). The three groups of recipients and GP subjects
      completed a French version of the questionnaire used by the National Institute of
      Diabetes and Digestive and Kidney Disease, Pittsburgh, PA, and were compared for
      each score, with adjustments for age and sex. RESULTS: Personal function and
      measures of disease by the transplant recipients were significantly worse than in
      the GP (P<0.0001), with the worst score in Kidney-R. No difference, either
      between organs or between organs and GP, was found regarding the perceived social
      and role function. However, for psychologic status and general health perception,
      Kidney-R had the least favorable performance when compared with GP (P<0.01) and
      also when compared with Liver-R (P<0.05). With the exception of Kidney-R, the
      well-being index of Liver-R and Heart-R was significantly better than the GP
      (P<0.001 and P<0.05, respectively). CONCLUSIONS: The QOL beyond 10 years after
      liver, heart, and kidney transplantation is quite similar to the GP, with Kidney
      R starting out as the worst, Heart-R as intermediate, and Liver-R the best.

PMID- 14688520
TI  - T-cell reconstitution after unmanipulated, CD8-depleted or CD34-selected
      nonmyeloablative peripheral blood stem-cell transplantation.
AB  - BACKGROUND: We have previously shown that CD8 depletion or CD34 selection of
      peripheral blood stem cells (PBSC) reduced the incidence of acute graft-versus
      host disease (GvHD) after nonmyeloablative stem-cell transplantation (NMSCT). In
      this study, we analyze the effect of CD8 depletion or CD34 selection of the graft
      on early T-cell reconstitution. METHODS: Nonmyeloablative conditioning regimen
      consisted in 2 Gy total-body irradiation (TBI) alone, 2 Gy TBI and fludarabine,
      or cyclophosphamide and fludarabine. Patients 1 to 18 received unmanipulated
      PBSC, patients 19 to 29 CD8-depleted PBSC, and patients 30 to 35 CD34-selected
      PBSC. RESULTS: T-cell counts, and particularly CD4+ and CD4CD45RA+ counts,
      remained low the first 6 months after nonmyeloablative stem-cell transplantation
      (NMSCT) in all patients. CD34 selection (P<0.0001) but not CD8 depletion of PBSC
      significantly decreased T-cell chimerism. Donor T-cell count was similar in
      unmanipulated compared with CD8-depleted PBSC recipients but was significantly
      lower in CD34-selected PBSC recipients (P=0.0012). T cells of recipient origin
      remained stable over time in unmanipulated and CD8-depleted PBSC patients but
      expanded in some CD34-selected PBSC recipients between day 28 and 100 after
      transplant. Moreover, whereas CD8 depletion only decreased CD8+ counts (P<0.047),
      CD34 selection reduced CD3+(P<0.001), CD8+(P<0.016), CD4+ (P<0.001), and
      CD4+CD45RA+ (P<0.001) cell counts. T-cell repertoire was restricted in all
      patients on day 100 after hematopoietic stem-cell transplantation but was even
      more limited after CD34 selection (P=0.002). CONCLUSIONS: Despite of the
      persistence of a significant number of T cells of recipient origin, T-cell counts
      were low the first 6 months after NMSCT. Moreover, contrary with CD8 depletion of
      the graft that only affects CD8+ lymphocyte counts, CD34 selection dramatically
      decreased both CD8 and CD4 counts.

PMID- 14688521
TI  - How to improve the quality of kidneys from non-heart-beating donors: a randomised
      controlled trial of thrombolysis in non-heart-beating donors.
AB  - BACKGROUND: The growth in the prevalence of end-stage renal failure has been
      accompanied with a rise in the waiting list for renal transplantation, which has
      not been matched by an increase in the kidney donor pool. Non-heart-beating
      donors (NHBD) offer a potential source of kidneys that are not currently being
      significantly used. Cardiac arrest for a protracted period of time leads to in
      situ thrombosis, and, as a consequence, the discard rates for harvested kidneys
      is higher than brain-stem-dead donors. METHODS: A double-blinded, randomised,
      controlled trial of streptokinase preflush or placebo for NHBD was performed. An
      initial 30 donors were entered into the study. After routine nephrectomy, NHBD
      kidneys were machine perfused as part of viability screening before
      transplantation. Kidneys were then transplanted within 24 hours of cardiac
      arrest. The primary objectives were the improvements of viability parameters
      (perfusion, enzyme levels, and histopathology) of the kidneys. The secondary
      objective was to increase the number of kidneys passing the viability tests and
      thus transplanted. RESULTS: The two groups of NHBD donors and their kidneys were
      similar in their descriptive epidemiologic characteristics. The NHBD kidneys from
      the streptokinase-treated donors had a better appearance at procurement (P<0.001)
      and performed better during machine preservation (P<0.001). Enzyme biomarkers
      present in the kidney perfusate were all significantly reduced by the use of
      streptokinase. These included glutathione S-transferase (P<0.001), fatty acid
      binding protein (P<0.001), and alanine aminopeptidase (P<0.001). However,
      although there was a higher proportion of kidneys transplanted through the use of
      streptokinase (63.6% with streptokinase vs. 42.6% with placebo), this did not
      achieve significance. There was no difference with respect to postoperative
      bleeding and transfusion requirements in the recipient whether streptokinase
      preflush or placebo was used. CONCLUSION: This study using streptokinase preflush
      in the NHBD was found to improve the condition of the kidneys retrieved. The
      improvement in the quality of the donor kidneys was not associated with an
      increased morbidity in the recipient.

PMID- 14688522
TI  - Phenotypic changes in lymphocyte subpopulations in pediatric renal-transplant
      patients after T-cell depletion.
AB  - BACKGROUND: T-cell depletion causes a novel homeostasis in lymphocyte subsets in
      adult transplant recipients. Little is known about long-term changes in pediatric
      patients. METHODS: Twenty-one pediatric renal-transplant patients (mean age 11.8
      years) were selected according to their initial postoperative immunosuppressive
      therapy: (1) baseline immunosuppression (BI) with cyclosporine, azathioprine, and
      steroids, n=11; and (2) BI plus polyclonal antibodies, n=10. Lymphocyte surface
      markers were measured in the mean 2.3 years after transplantation and analyzed
      between the patient groups and in regard to 46 age-matched healthy controls.
      RESULTS: The patient groups did not differ with respect to age, sex, renal
      function, and previous infections. Total lymphocyte counts, CD4+ T-cell numbers,
      and distribution of naive to memory CD4+ T cells were not different between
      transplant groups and controls. However, patients with postoperative T-cell
      depletion showed significantly lower ratios of CD4+ to CD8+ T cells, elevated
      CD8+ T-cell numbers, increased counts of CD8+ T cells coexpressing CD57, and
      higher numbers of CD8+ cells with a naive phenotype. In addition, the numbers of
      double-positive T cells and lymphocytes bearing both natural killer (NK) and T
      cell markers were elevated in the patients with postoperative depletion. NK and B
      cell counts were lower in the transplant patient groups compared with the healthy
      controls. CONCLUSIONS: Pediatric transplant patients show characteristic long
      term changes in lymphocyte subsets after T-cell depletion. In contrast with adult
      patients, these perturbations are less pronounced and predominant in the CD8+ T
      cell compartment.

PMID- 14688523
TI  - Vasopressor agents without volume expansion as a safe alternative to venovenous
      bypass during cavaplasty liver transplantation.
AB  - BACKGROUND: Cavaplasty orthotopic liver transplantation (OLT) offers advantages
      for hepatectomy and implantation and eliminates the risk of outflow obstruction.
      However, it does require clamping of the cava. This study describes the use of a
      vasopressor without fluid expansion or venovenous bypass (VB) for hemodynamic
      control during the anhepatic phase. METHODS: The cavaplasty OLT technique was
      used routinely. A vasopressor was administered if the mean arterial blood
      pressure (MAP) was less than 60 mm Hg after clamping of the cava. If the MAP did
      not reach 60 mm Hg after adjusting the dosage of the vasopressor, femoro-axillary
      VB would be used. VB was also indicated for preexisting cardiac disease or for
      massive hemorrhage from severe portal hypertension and extensive adhesions.
      RESULTS: Among all the 121 adult cavaplasty OLTs, 33 were supported with VB and
      50 received a vasopressor. The remaining 38 were excluded. However, baseline
      variables were well matched, except that preexisting cardiac disease was more
      frequent in the VB group. The median dosage of epinephrine was 0.07 microg/kg/min
      (range 0.01-0.6). The VB and vasopressor groups were similar in the reduction in
      mean MAP and the accumulation in arterial lactate upon clamping as well as in the
      central venous pressure upon unclamping. Postreperfusion hypotension was more
      frequent in the VB than in the vasopressor group (27.3% vs. 4.0%, P=0.006). There
      was no primary graft nonfunction or intraoperative right heart failure. One
      patient in the vasopressor group required postoperative temporary dialysis.
      Ninety-day patient and graft survival for the VB and vasopressor groups were
      97.0% vs. 98.0% and 97.0% vs. 94.0%, respectively. CONCLUSION: Modest doses of
      vasopressor without volume expansion or VB can maintain hemodynamic stability
      during the anhepatic phase of cavaplasty OLT.

PMID- 14688524
TI  - The impact of sirolimus, mycophenolate mofetil, cyclosporine, azathioprine, and
      steroids on wound healing in 513 kidney-transplant recipients.
AB  - BACKGROUND: The aim of this study was to determine whether there has been an
      increase in the incidence or severity of wound-healing complications that can be
      attributed to the introduction of newer immunosuppressive drugs. METHODS:
      Consecutive series of adult kidney-only transplant recipients were selected from
      our Unified Transplant Database backward from September 2002. There were 513
      patients divided into groups on the basis of their maintenance immunosuppression
      given for at least the first 30 days posttransplant. Group I (152) was given
      sirolimus, mycophenolate mofetil, and prednisone (SRL/MMF/P) between March 2000
      and September 2002; group II (168) was given cyclosporine A (CsA)/MMF/P between
      January 1999 and July 2002; and group III (193) was given azathioprine
      (AzA)/CsA/P between January 1993 and December 1997. A classification system for
      wound-healing problems was developed, and each of the three groups was analyzed
      by univariate and multivariate analysis. RESULTS: From groups III to II to I,
      there was a significant increase in mean age (42.4 vs. 49 years), percent of
      patients diabetic (17% vs. 29%), mean body mass index (BMI) (24.2 vs. 27.1
      kg/m2), and percent BMI greater than 30 (13.5% vs. 27%). The cumulative
      percentage of all wound-healing problems between group I (19.7%) vs. group II
      (16.1%) and group III (15.6%) was not significantly different. The most
      significant risk factor was a recipient BMI greater than 30 (P=0.0012) and
      delayed graft function (P=0.0041). CONCLUSIONS: During a 10-year period marked by
      changing recipient demographics, the introduction of MMF and SRL did not result
      in a significant increase in transplant wound-healing complications. The most
      significant risk factor associated with transplant wound-healing complications
      remains body weight, which was the major influence for each of the
      immunosuppressive drug combinations described.

PMID- 14688525
TI  - Mycophenolate mofetil increases adhesion capacity of tumor cells in vitro.
AB  - BACKGROUND: The immunosuppressive drug mycophenolate mofetil (MMF) reduces
      expression of the heterophilic binding elements intercellular adhesion molecule-1
      and vascular cell adhesion molecule-1 and thereby prevents attachment of
      alloactivated leukocytes to donor endothelium. The authors speculated that MMF
      might further diminish receptors of the immunoglobulin superfamily which,
      however, act as homophilic binding elements. Because decrease of homophilic
      adhesion receptors correlates with tumor dissemination and metastasis, MMF could
      trigger development or recurrence of neoplastic tumors. METHODS: The authors
      analyzed the influence of MMF on homotypic adhesion receptors and its consequence
      for tumor cell attachment to an endothelial cell monolayer. Neuroblastoma (NB)
      cells, which self-aggregate by means of the homophilic-binding element neural
      cell adhesion molecule (NCAM), were used. Effects of MMF on the 140- and 180-kDa
      NCAM isoforms were investigated quantitatively by flow cytometry, Western blot,
      and reverse-transcriptase (RT) polymerase chain reaction (PCR). The relevance of
      NCAM for tumor cell binding was proven by treating NB with NCAM antisense
      oligonucleotides. RESULTS: MMF profoundly increased the number of adherent NB
      cells, with a maximum effect at 0.1 microM, compared with controls. Decrease of
      NCAM on the cell surface was detected by flow cytometry. Western blot and RT-PCR
      demonstrated reduced protein and RNA levels of the 140- and 180-kDa isoforms.
      Treatment of NB cells with NCAM antisense oligonucleotides showed that reduced
      NCAM expression leads to enhanced tumor cell adhesion. CONCLUSIONS: MMF decreases
      NCAM receptors, which is associated with enhanced tumor cell invasiveness. The
      authors conclude that an MMF-based immunosuppressive regimen might increase the
      risk of tumor metastasis if this process is predominantly conveyed by means of
      homophilic adhesion proteins.

PMID- 14688526
TI  - Tumour necrosis factor receptor type II 196M/R genotype correlates with
      circulating soluble receptor levels in normal subjects and with graft-versus-host
      disease after sibling allogeneic bone marrow transplantation.
AB  - BACKGROUND: A single nucleotide polymorphism in the tumor necrosis factor type II
      receptor (TNFRII) gene, codon 196, results in the substitution of arginine (R
      allele) for methionine (M allele). The 196R allele is reportedly associated with
      an increased susceptibility to autoimmune disease, and donor 196R allele carriage
      correlates with increased severity of acute graft-versus-host disease (GVHD)
      after matched unrelated bone marrow transplantation (BMT). METHODS: We
      investigated the impact of donor and recipient TNFRII genotype on GVHD incidence
      and severity among 104 adult recipients of myeloablative sibling BMTs. RESULTS:
      196R allele frequency was 0.28 among recipients, donors, and controls. There was
      an increased incidence of acute GVHD among 196R-positive recipients (odds ratio
      [OR] 3.6, P=0.05). This association was confirmed in multivariate analysis
      (relative risk 4, P=0.04), correcting for previously established clinical and
      genetic risk factors. Donor 196R homozygosity was associated with an increased
      incidence of extensive chronic GVHD (OR 18.5, P=0.02). This association was also
      confirmed in multivariate analysis (OR 11, P=0.02). To investigate the functional
      impact of the TNFRII 196 M/R polymorphism, 79 volunteer blood donors were
      genotyped at this locus, by polymerase chain reaction and single-strand
      conformational polymorphism analysis, and plasma soluble TNFRII (sTNFRII) levels
      were measured by ELISA. Mean plasma sTNFRII levels (pg/mL: +/-SEM) were 1224 (+/
      26) and 1063 (+/-65) for 196M-postive (196 M homozygous or heterozygous)
      individuals and 196R homozygotes, respectively (P=0.02). CONCLUSIONS: Because
      sTNFRIIs can act as TNF antagonists, the association between recipient and donor
      TNFRII 196R allele status and acute or extensive chronic GVHD incidence,
      respectively, may reflect reduced circulating sTNFRII.

PMID- 14688527
TI  - Analysis of cytokine functions in graft rejection by gene expression profiles.
AB  - BACKGROUND: The function of interferon (IFN)gamma in the regulation of the immune
      response after allogeneic transplantation is still poorly understood. Previous
      studies have suggested that IFNgamma can promote rejection and be important in
      tolerance induction. METHODS: To analyze the various IFNgamma-dependent functions
      in terms of T helpers 1 and 2 responses during rejection, we investigated mice
      deficient in the transcription factors (signal transducer of activated T cells
      [STAT]4 and 6) and IFNgamma in fully major histocompatibility complex-mismatched
      vascularized cardiac transplants. Serum levels of the cytokines tumor necrosis
      factor-alpha, IFNgamma, and interleukin (IL)-1beta were evaluated by enzyme
      linked immunosorbent assay, and the graft-infiltrating cells were examined by
      immunohistochemical staining. To analyze a large panel of immune parameters, we
      determined the expression of chemokines, chemokine receptors, and clusters of
      differentiation markers by RNAase protection assays. The data were analyzed with
      algorithms that generated hierarchic clustering dendrograms. Also, the expression
      profiles of individual genes were determined with self-organizing maps. RESULTS:
      Our data show that both the STAT4- and STAT6-deficient groups have statistically
      prolonged graft survival (P<0.04 and P<0.01). Despite the absence of prolongation
      of graft survival in the IFNgamma-deficient group, our analysis of variance data
      show that more genes (18) were modulated in the IFNgamma-deficient group compared
      with the other two STAT4- and STAT6-deficient groups (five each). CONCLUSIONS:
      Our results indicate that IFNgamma plays a distinct role in the modulation of
      gene expression that includes STAT4-independent mechanisms. Our study identifies
      eight genes (IL-1beta, IL-1RA, macrophage inflammatory protein-1beta, monocyte
      chemoattractant protein-1, CC-chemokine receptor (CCR)-1, CCR2, CCR5, and F4/80)
      that are highly expressed in all of our experimental groups. Thus, these genes
      become candidates for essential functions during rejection.

PMID- 14688528
TI  - High-producer interleukin-2 genotype increases risk for acute graft-versus-host
      disease after unrelated donor bone marrow transplantation.
AB  - BACKGROUND: Cytokine polymorphisms may modulate immunologic reactivity, including
      graft-versus-host disease (GVHD). A single nucleotide polymorphism resulting in a
      thymine-to-guanine transition in the interleukin (IL)-2 gene promoter region
      occurs at position -330. In vitro studies have shown that the G allele is
      associated with early and sustained enhancement of IL-2 production, a so-called
      high-producer genotype. Because IL-2 is a proinflammatory cytokine, we
      hypothesized that recipients with high-producer genotypes would have increased
      frequency of GVHD after allogeneic bone marrow transplantation (BMT). METHODS: We
      studied 95 consecutive donor and recipient pairs who received an unrelated donor
      BMT at the University of Minnesota. The median age at time of BMT was 14.1 years
      (range 0.9-54.8 years). Stem cells were human leukocyte antigen-A, B, and DRB1
      matched in 70 cases (74%) and single-antigen mismatched in 25 cases (26%). GVHD
      prophylaxis consisted of cyclosporine-containing regimens (53%), T-cell depletion
      by elutriation (42%), and others (2%). RESULTS: The probability of grade II-IV
      acute GVHD at day 100 was 36% (95% confidence interval 26%-46%) and was
      significantly affected by the presence of recipient IL-2 G allele. The
      probability of acute GVHD was 49% in 49 patients (52%) with at least one G allele
      compared with 24% in 42 patients (44%) with no G allele (P<0.01). In the Cox
      regression analysis, the presence of at least one IL-2 G allele was associated
      with a twofold increased risk of acute GVHD. CONCLUSIONS: If confirmed by others,
      our results indicate that more intensive GVHD prophylaxis is needed for patients
      with at least one IL-2 G allele, possibly directed toward blunting early host
      cell production of IL-2.

PMID- 14688529
TI  - Induction of tolerance in a rat model of laryngeal transplantation.
AB  - BACKGROUND: The major limitation preventing expansion of laryngeal
      transplantation as a therapeutic modality is the necessity of lifelong
      immunosuppression. In this report, we describe an immunomodulatory strategy for
      tolerance induction in laryngeal allotransplantation that permits escape from
      chronic immunosuppression. MATERIALS AND METHODS: Larynges were transplanted from
      Lewis-Brown-Norway (RT1l/n, F1) donors to Lewis (RT1l) recipients. Recipients
      received 7 days of treatment with tacrolimus and mouse anti-rat alphabeta T-cell
      receptor (TCR) monoclonal antibodies. Histology, mixed lymphocyte reaction (MLR),
      skin grafting, and flow cytometry assessed functional tolerance, efficacy of
      immunodepletion, and donor-specific chimerism. RESULTS: All 10 recipients
      survived until sacrifice at 100 days. Histology suggested functional allograft
      tolerance. Skin grafting, MLR, and flow cytometry revealed that tolerance is
      neither donor-specific nor related to systemic immunocompromise. CONCLUSIONS: In
      this rat laryngeal-transplantation model, functional tolerance was induced under
      combined tacrolimus and alphabeta TCR protocol. Mechanisms responsible for this
      tolerance induction require future elucidation.

PMID- 14688530
TI  - Sirolimus inhibits oxidative burst activity in transplant recipients.
AB  - Increased susceptibility to bacterial infection is a recognized side-effect of
      sirolimus treatment after transplantation, which could be caused by inhibition of
      neutrophil activation. Blood from 24 healthy subjects was equilibrated with 0 to
      50 ng/mL sirolimus or 60 microg/mL propofol. Blood was also collected from 23
      transplant recipients (13 kidney, 10 liver) with renal impairment, randomized to
      remain on calcineurin inhibitors (n=12) or to be switched to sirolimus
      monotherapy (n=11). Phorbol myristate acetate (PMA)-stimulated oxidative burst
      was measured by flow cytometry at 0 and 3 months after randomization. There was a
      linear relationship between inhibition of neutrophil activation in vitro and
      sirolimus concentrations spanning the therapeutic range (P=0.01). Neutrophil
      activation was decreased significantly in transplant recipients 3 months after
      switching from calcineurin inhibitors to sirolimus therapy (mean percentage
      change -24.4%; 95% confidence interval -7.5, -41.2%, P=0.009), but no changes
      were observed in patients who remained on calcineurin inhibitors.

PMID- 14688531
TI  - Changes in serum levels of hepatocyte growth factor in patients undergoing adult
      to-adult living-donor liver transplantation.
AB  - Changes in the serum concentration of hepatocyte growth factor (HGF), a potent
      mitogen for hepatocytes, were investigated in adult-to-adult living-donor liver
      transplantation (LDLT) in which liver regeneration is involved. Between August
      2000 and November 2002, 15 consecutive adult-to-adult LDLTs were performed using
      the right lobe graft. The recipients were divided into two groups: acute liver
      failure (n=6) and chronic liver failure (n=9). In addition, right lobe donors
      (n=12) were evaluated. Measurement of HGF was performed on preoperative and
      postoperative days 1, 3, 7, and 14 after LDLT. The pretransplant levels of serum
      HGF were higher in the acute liver failure group than in the chronic liver
      failure group (P<0.05). After liver replacement, serum HGF levels normalized
      rapidly in both groups and remained rather low. Despite vigorous liver
      regeneration in all groups, serum HGF levels did not change significantly after
      adult-to-adult LDLT with right lobe graft.

PMID- 14688532
TI  - Renal transplantation and immunosuppressive therapy do not contraindicate stem
      cell donation for bone-marrow transplantation.

PMID- 14688533
TI  - A clinical renal-transplant case from a non-heart-beating donor using
      percutaneous cardiopulmonary support.

PMID- 14688534
TI  - Sirolimus myopathy.

PMID- 14688535
TI  - Failure of endovascular abdominal aortic aneurysm graft limb in a kidney
      transplant patient: a case report.

PMID- 14688536
TI  - Methylenetetrahydrofolate reductase C677T polymorphism and toxicity in allogeneic
      hematopoietic cell transplantation.

PMID- 14688537
TI  - A systematic search for anti-food IgEs in organ donors is needed.

PMID- 14688538
TI  - Tacrolimus and food allergy.

PMID- 14688541
TI  - Reversibility of corneal pigmented arc associated with orthokeratology.
AB  - Corneal pigmented (brown) arcs were observed in two orthokeratology patients,
      both aged 23 years. The preorthokeratology refractive data were OD -5.25 -0.50 x
      175 and OS -6.00 -0.75 x 5 for patient A and OD -3.75 -1.00 x 10 and OS -3.00 
      1.25 x 175 for patient B. The time course for the development of the arcs was
      different not only between the two patients but also between the two eyes of
      patient A. For patient A, the pigmented arc was observed in the left eye 1 week
      after commencement of lens wear and was not observed in his right eye until a
      visit about 6 weeks later. For patient B, the arcs were only observed at an
      aftercare visit about 28 weeks after commencing lens wear. Both patients had been
      participating in an orthokeratology research study for about 12 months and
      decided to stop the treatment after completion of the study. The pigmented arcs
      were no longer present when they returned about 2 months later for assessment of
      the regression of the refractive and corneal changes induced by the procedure.

PMID- 14688542
TI  - Comparison of reverse-geometry lens designs for overnight orthokeratology.
AB  - PURPOSE: The efficacy of overnight wear of four types of reverse-geometry lenses
      was compared. The length of time needed to achieve correction and any adverse
      events that occurred during the course of the study were recorded. METHODS: In
      this prospective, randomized study, 60 subjects (18 to 35 years old) with
      refractive error between -1.00 to -4.00 D (cyl </= -1.50) wore reverse-geometry
      lenses overnight only. All subjects were assigned a Rinehart Reeves lens in one
      eye, and subsets of 20 subjects were randomly assigned a Mountford BE, DreimLens,
      or Contex D Series 4 lens for the contralateral eye. Visits included baseline,
      dispensing, 1 day, 1 week, and 1 month. Biomicroscopy, unaided visual acuity,
      subjective refraction, best-corrected visual acuity at high and low contrast and
      high and low illumination, corneal topography, and subjective rating data were
      collected. RESULTS: Forty-six subjects completed the study. At 1 month, there
      were no significant differences between lens types in their effect on unaided
      visual acuity, subjective sphere, subjective cylinder, best-corrected visual
      acuity at high and low contrast at high illumination and low contrast at low
      illumination, apical corneal radius, corneal eccentricity, and subjective
      ratings. Between 1 week and 1 month, there was a significant improvement in
      subjective ratings of quality of day and night vision (p < 0.05) but no
      significant change in the objective measures. No significant ocular adverse
      events were observed during the trial. CONCLUSIONS: The lens types tested were
      all similarly effective in the reduction of myopic refractive error. Subjective
      ratings continued to improve after objective measures stabilized at 1 week.
      Overnight lens wear proceeded for 1 month without significant adverse reactions.

PMID- 14688543
TI  - Higher-order wavefront aberrations in corneal refractive therapy.
AB  - PURPOSE: To assess the changes in higher-order (third through sixth) ocular
      wavefront aberrations produced by Corneal Refractive Therapy (CRT; Paragon Vision
      Sciences, Mesa, AZ). METHODS: Eighteen eyes of nine myopic subjects were fit with
      CRT contact lenses. Baseline subjective spherical refraction ranged from -2.25 to
      -6.00 D (mean +/- SD, -3.33 +/- 1.26 D), and baseline logarithm of the minimum
      angle of resolution (logMAR) best-corrected visual acuity was -0.13 +/- 0.06
      (20/15 Snellen equivalent). Whole-eye ocular wavefront aberrations were measured
      using a previously validated Shack-Hartmann aberrometer. Measurements were taken
      at baseline and 1 month after treatment initiation. Nine measurements per dilated
      subject were taken and averaged. Zernike coefficients were used to calculate the
      third-, fourth-, fifth-, and sixth-order root-mean-square values for each eye for
      both 3- and 6-mm pupil sizes, and aberrations were averaged and compared with
      prior baseline readings. RESULTS: The mean (+/-SD) myopia reduction was 3.08 +/-
      0.93 D, resulting in a subjective refraction of -0.22 +/- 0.38 D after 1 month of
      lens wear. Both logMAR uncorrected visual acuity (-0.07 +/- 0.18; 20/15- Snellen
      equivalent) and best-corrected visual acuity (-0.14 +/- 0.09) after CRT wear were
      not significantly different from baseline logMAR best-corrected visual acuity
      (paired two-tailed t-test; p = 0.41 and 0.65, respectively). Whole-eye
      aberrations showed a statistically significant increase in higher-order
      aberrations for both 3-mm (factor of 2.66; p = 0.01) and 6-mm pupils (factor of
      2.50; p = 0.005). Each individual higher-order aberration also increased, ranging
      from a factor of 2.01 to 3.20 for 3-mm pupil sizes and 2.52 to 2.98 for 6-mm
      pupil sizes. Spherical-like aberrations (S4 and S6) increased by a factor of 1.79
      for 3-mm pupil sizes and 2.42 for 6-mm pupil sizes. The Zernike coefficient most
      affected by CRT was spherical aberration (Z40), which increased from 0.084 +/-
      0.16 to 0.39 +/- 0.16 microm (p = 0.0002) for 6-mm pupils. CONCLUSIONS: Use of
      current CRT lenses for the reduction of myopia increased higher-order wavefront
      aberrations and spherical aberration (Z40) in particular.

PMID- 14688544
TI  - Predicting and assessing visual performance with multizone bifocal contact
      lenses.
AB  - PURPOSE: To investigate how bifocal contact lenses, when combined with the
      aberrations of the eye, will affect visual performance. Also, to investigate the
      relationship between the patient's predicted and actual visual benefit with
      bifocal contact lenses. METHODS: The monochromatic aberrations of 16 subjects
      were measured and used to simulate visual quality with three bifocal contact lens
      designs. Actual and computed visual benefit was compared for an Acuvue bifocal
      contact lens in 5 of the 16 subjects. RESULTS: Subjects were predicted to have
      either a bifocal response or an increase in depth of focus for all lens designs.
      Our subjects were predicted to have a decrease in visual benefit for distance
      viewing and a gain in visual benefit at near compared with not wearing a contact
      lens. We found a statistically significant association between our subjects'
      predicted and actual visual benefit with the Acuvue Bifocal contact lens (r =
      0.685, p = 0.008). CONCLUSIONS: Bifocal contact lens designs, when combined with
      the aberrations of the eye, will not always provide bifocal vision. Visual
      quality with a bifocal contact lens can be predicted based on a patient's ocular
      aberrations.

PMID- 14688545
TI  - Interexaminer difference and the effect of training on the phenol red thread test
      results in Hong Kong-Chinese.
AB  - PURPOSE: This study evaluated interexaminer agreement in the measurement of tear
      volume using the phenol red thread (PRT) test on Hong Kong-Chinese subjects. The
      effect of an intensive training session on interexaminer agreement was also
      investigated. METHODS: Three postgraduate students without an optometry
      background were introduced to the use of the PRT test. After a general
      introduction (including a demonstration and some practice among themselves), the
      examiners collecting the first set of data from 38 subjects. They were then given
      an intensive 30-min training that involved strict standardization of
      instructions/procedures and practice. PRT values were collected from 27 subjects
      (four subjects participated in both phases of the study) after the intensive
      training. RESULTS: Significant differences were found among the examiners before
      and after the intensive training, which was mainly due to examiner 1, who
      consistently obtained relatively lower mean PRT values in both testing sessions.
      The intraclass correlation values estimated for all examiners were 0.35 and 0.58
      before and after the training session, respectively. The 95% limits of agreement
      after the training session ranged from -14.8 to 8.0 mm/15 s between examiners 1
      and 3, who showed the largest difference, and from -8.8 to 9.3 mm/15 s between
      examiners 2 and 3, who showed the smallest difference. The latter pair also
      showed the most significant increase in agreement after the intensive training
      (intraclass correlation value increase from 0.29 to 0.65), although no
      significant differences in the PRT results were found between the two examiners
      before and after training. CONCLUSIONS: Our results suggest that the
      interexaminer agreement of PRT results is influenced by both examiner- and
      training-specific factors. Intensive training is important for ensuring the
      highest consistency among examiners. The moderate interexaminer agreement
      suggests that clinicians should seek a substantial difference in tear volume when
      making decisions regarding interventions for their Hong Kong-Chinese patients.

PMID- 14688546
TI  - The effect of artificial tears on visual performance in normal subjects wearing
      contact lenses.
AB  - PURPOSE: Disruption of the anterior refracting surface of the eye reduces visual
      performance. In the case of a contact lens wearer, this surface is the prelens
      tear film. This study determined whether artificial tears stabilize the tear film
      in contact lens wearers and maintained optimal visual performance for a prolonged
      period. METHODS: Five normal subjects all in good general and ocular health and
      adapted to contact lens wear were fitted with Acuvue lenses. A temporal, two
      alternative, forced-choice paradigm was used to measure contrast sensitivity. The
      stimuli were vertically oriented sine-wave gratings (between 0.5 and 14 cpd)
      presented for 16.67 ms. The stimuli were presented at two different times after
      blink detection: 2 s after blink detection (i.e., before tear layer break-up) or
      4 s after tear film break-up. Three conditions were investigated at 4 s after
      tear layer break-up: (1) without artificial tears added, (2) with Clerz2 (Ciba
      Vision) instilled, and (3) with Sensitive Eyes (Bausch & Lomb) applied. The
      artificial tears were instilled at 10-min intervals during the experimental run.
      RESULTS: High spatial frequency contrast sensitivity was found to be reduced
      after tear film break-up and was not enhanced by either tear solution.
      CONCLUSIONS: This study indicates that there is no effect of Clerz2 or Sensitive
      Eyes in maintaining or improving visual performance beyond the normal prelens
      tear film break-up time in normal subjects wearing Acuvue lenses.

PMID- 14688547
TI  - Validity and reliability of the revised convergence insufficiency symptom survey
      in children aged 9 to 18 years.
AB  - PURPOSE: To assess the validity and reliability of the Convergence Insufficiency
      Symptom Survey (CISS) in children aged 9 to 18 years. The CISS is the primary
      outcome measure for a pilot study evaluating two different treatments for
      convergence insufficiency (CI). METHODS: Children with CI were given the CISS
      twice to assess reliability. CISS scores for the first administration were also
      compared with scores from children with normal binocular vision to assess the
      validity of the CISS. RESULTS: Forty-seven children with CI and 56 children with
      normal binocular vision participated in the study. Reliability was assessed using
      intraclass correlation and 95% limits of agreement for the children with CI. For
      children with CI, the intraclass correlation was 0.77 (95% confidence interval,
      0.613 to 0.873), and the 95% limits of agreement were -10.2 to +12.1. The mean
      (+/-SD) CISS score was 30.8 +/- 8.4 for the children with CI and 8.4 +/- 6.4 for
      the children with normal binocular vision. These means were significantly
      different (p < 0.0001). Good discrimination (sensitivity, 96%; specificity, 88%)
      was obtained using a score of >/=16. CONCLUSIONS: Children with CI showed a
      significantly higher CISS symptom score than children with normal binocular
      vision. The results of the study indicate that the CISS is a valid and reliable
      instrument to use as an outcome measure for children aged 9 to 18 who are
      enrolled in clinical research concerning CI.

PMID- 14688548
TI  - Tolerancing and budget in design and production of test lenses for calibration of
      focimeters.
AB  - A focimeter is one of the basic clinical instruments used in every optometric
      practice, and verification of the accuracy and calibration of the instrument are
      of the utmost importance. Calibration is accomplished using special test lenses.
      These lenses must be of high quality and of nominal ophthalmic power that is
      known with high accuracy. The standard ISO 9342:1996 Optics and Optical
      Instruments: Test Lenses for Calibration of Focimeters imposes stringent
      requirements on permitted deviation from nominal ophthalmic power of test lenses.
      In this study, the influence of tolerancing and uncertainties in design and
      production of standard test lenses for calibration of focimeters was analyzed.
      Two approaches were used. First, the paraxial approximation was used to relate
      the lens parameters with ophthalmic power and to calculate the uncertainty
      budget. Second, exact ray tracing using a professional optical design program and
      tolerancing sensitivity analysis in conjunction with Monte Carlo simulation were
      used to evaluate the uncertainty budget and balance the required tolerances. The
      results of both approaches are compared and discussed in detail. The customary
      uncertainty budgeting based on simple paraxial approximation does not guarantee
      the compliance with the requirements of the ISO 9342:1996 standard. Consequently,
      such an approach is inadequate for characterization and tolerancing of test
      lenses for calibration of focimeters.

PMID- 14688551
TI  - The changing distribution of arm circumferences in NHANES III and NHANES 2000 and
      its impact on the utility of the 'standard adult' blood pressure cuff.
AB  - BACKGROUND: Accurate blood pressure measurement is dependent on using a blood
      pressure cuff that is appropriate to the patient's arm circumference. OBJECTIVE:
      This study identifies the change in distribution of arm circumferences in the
      United States and its impact on usage of the 'standard adult' cuff. METHOD: The
      most current National Health and Nutritional Examination Survey (NHANES) data,
      available on the website (http://www.cdc.gov/nchswww/nchshome.htm), covers NHANES
      III (Cycle 1, 1988-1991; 8381 subjects and Cycle 2, 1991-1994; 8566 subjects) and
      NHANES 2000 (1999-2000; 4,444 subjects). The weighted change in arm circumference
      between NHANES III as a whole and NHANES 2000 was calculated. Correlates for
      increased arm circumference were obtained via multivariate analysis. The
      predicted change in blood pressure cuff usage based on the changing prevalence of
      arm circumferences was calculated. RESULTS: The mean arm circumference for the
      whole population increased significantly from NHANES III to NHANES 2000 (31.83 +/
      0.08 cm versus 32.86 +/- 0.15 cm, p < 0.001) and in the hypertension population
      without reaching statistical significance (33.07 +/- 0.16 to 33.61 +/- 0.30 cm, p
      = 0.11). When adjusted regressions were performed, the increases in arm
      circumference were due to increasing weight in both the whole population and the
      hypertensives. The numbers of Americans predicted to require the 'standard adult'
      cuff to accurately measure blood pressure decreased from 76.2% to 66.3% while the
      number of Americans increased from 42.2% to 45%. CONCLUSIONS: The increasing
      prevalence of overweight and obese Americans found in NHANES III and NHANES 2000
      has led to larger mean arm circumferences in hypertensives and the total
      population. This increased frequency of larger arm circumferences predicts that
      the 'large adult' cuff will be increasingly required in clinician's offices for
      accurate blood pressure measurement.

PMID- 14688552
TI  - Validation of a two-axis accelerometer for monitoring patient activity during
      blood pressure or ECG holter monitoring.
AB  - OBJECTIVES: The aim of the study was to evaluate the efficiency of a
      position/activity monitoring system based on a dual-axis accelerometer strapped
      to the subject's thigh and a position sensor located within a monitor placed on
      the subject's belt. METHODS: Twenty-six subjects wearing two monitors (one
      accelerometer on each thigh) were submitted to various activities and positions
      under the control of an observer. An analysis of each tracing was performed both
      manually by a technician and automatically by dedicated software before being
      compared with the information gathered during the study. RESULTS: The
      accelerometer allowed accurate discrimination between the standing versus the
      sitting and lying positions. The sitting and lying positions were correctly
      detected by the built-in position sensor provided the unit was firmly attached.
      Walking was adequately detected by the accelerometer. The activity score was well
      correlated with treadmill speed. Changes in position and activity were detected
      with a mean error of less than 3 s. CONCLUSIONS: The combination of an
      accelerometer placed on the subject's thigh and a position sensor located at the
      subject's waist appeared to be a suitable system for position/activity monitoring
      during ambulatory ECG and blood pressure monitoring.

PMID- 14688553
TI  - Job strain and physiological stress responses in nurses and nurse's aides:
      predictors of daily blood pressure variability.
AB  - BACKGROUND: Job strain has been implicated in risk of cardiovascular disease, and
      there is evidence for increased blood pressure among men with job strain. It is
      unclear, however, to what degree job strain affects blood pressure in women. This
      study examined the relationships between job strain, norepinephrine and
      epinephrine excretion in the workplace, and ambulatory blood pressure variability
      during waking hours in women working as nurses or nurse's aides in Hilo, Hawaii.
      METHODS: Women from two ethnic groups, Filipino-Americans (n = 36) and Euro
      Americans (n = 23), were measured on a workday, urinary catecholamine excretion
      and ambulatory blood pressure being measured over a 4-h period at work and home,
      and overnight over an 8-h period. The rates of catecholamine excretion were
      measured in timed urine samples using high-performance liquid chromatography with
      electrochemical detection, and ambulatory blood pressure was measured at 15-min
      intervals using a SpaceLabs 90207 monitor. The women filled out the Job Content
      Questionnaire prior to the physiological measurements. RESULTS: Scores on the Job
      Content Questionnaire were not significantly associated with the physiological
      measures, although correlations were higher for Euro-American participants than
      Filipino-Americans. Catecholamine excretion rates in the workplace were
      significantly related to blood pressure variability throughout the day and to
      systolic blood pressure means, but catecholamine excretion rates in other daily
      settings were not significantly related to blood pressure. CONCLUSIONS: These
      results support the idea that stress in the workplace has special significance
      for the prediction of cardiovascular health risk, and that catecholamine
      excretion at work is significantly associated with increased blood pressure
      variability during the day. Job strain, as measured by subscales from the Job
      Content Questionnaire, was not associated with any of the physiological measures.
      This lack of association may be the result of ethnic and circumstantial bias in
      the questionnaire, suggesting that job strain should be evaluated in a more
      critical manner in populations differing from the ones in which the concept was
      developed.

PMID- 14688554
TI  - The use of peridialysis blood pressure and intradialytic blood pressure changes
      in the prediction of interdialytic blood pressure in haemodialysis patients.
AB  - OBJECTIVE: It is uncertain which blood pressure values (pre- or post
      haemodialysis) best represent the average daily blood pressure in haemodialysis
      patients. The purpose of this study was to verify the power of peridialysis blood
      pressure to predict interdialytic blood pressure, and to ascertain the influence
      of blood pressure fluctuations during dialysis on this predictive ability.
      METHODS AND RESULTS: We performed ambulatory blood pressure monitoring during the
      interdialytic period on 60 stable haemodialysis patients (mean age 53 +/- 16
      years, 33 male) between two mid-week haemodialysis sessions. Pre- and post
      haemodialysis blood pressures were 154/82 and 142/77 mmHg, respectively, and 44-h
      interdialytic blood pressure was 136/77 mmHg. Overall, post-haemodialysis blood
      pressure values correlated with interdialytic ambulatory blood pressure
      marginally better than did pre-haemodialysis values (r = 0.52 versus 0.61 for pre
      and post-dialysis systolic pressure, respectively; r = 0.67 versus 0.72 for pre-
      and post-dialysis diastolic pressure, respectively). The average of the pre- and
      post-haemodialysis values showed a slightly better correlation with interdialytic
      blood pressure (r = 0.65 and 0.75 for systolic and diastolic pressure,
      respectively). When we stratified patients according to systolic blood pressure
      behaviour during dialysis, pre-dialysis blood pressure was the stronger predictor
      of interdialytic blood pressure in the quartile with greatest intradialytic blood
      pressure fall (r = 0.67 versus 0.44 for pre- and post-dialysis systolic blood
      pressure, respectively), whereas post-dialysis values were substantially better
      in the group with a rise in systolic pressure during dialysis (r = 0.26 versus
      0.59 for pre- and post-dialysis systolic blood pressure, respectively).
      CONCLUSIONS: These data demonstrate that peridialysis blood pressure values are
      of limited accuracy in predicting interdialytic blood pressure, post-dialysis
      values are minimally better predictors than pre-dialysis blood pressures, and the
      average of pre- and post-haemodialysis values is marginally better than both. In
      addition, blood pressure fluctuations during dialysis have a sizable impact on
      this predictive ability. Clinical decisions related to blood pressure management
      and research design in haemodialysis hypertension should take these factors into
      account.

PMID- 14688555
TI  - Primary care physician beliefs regarding usefulness of self-monitoring of blood
      pressure.
AB  - BACKGROUND: Recent studies suggest that the self-monitoring of blood pressure
      (SMBP) may improve the identification and control of hypertension. Although
      endorsed by the Joint National Committee VII guidelines, home monitoring is not
      currently part of the standard care of hypertension. OBJECTIVE: To assess
      community- and university-based primary care physicians' opinions of SMBP.
      METHODS: A written, 5-point, Likert-scale questionnaire was mailed to physicians
      in a primary care research network. RESULTS: We received completed surveys from
      138 of 170 providers (81%). Physician ages ranged from 25 to 72 years. Half of
      the providers were female, and approximately half were residents. Most physicians
      (63%) reported having patients using SMBP. Physician opinions of SMBP were
      unrelated to age, gender and number of years in practice. Three key beliefs were
      expressed: SMBP could be useful, economical and problematic. Community-based
      physicians were more likely than university-based physicians to believe in the
      benefits of SMBP use, and to disagree that the use of SMBP could cause problems
      for them or their patients (P < 0.05). Compared with their peers, physicians with
      fewer than five patients using SMBP agreed more strongly with statements that
      SMBP use could cause problems for themselves and their patients in hypertension
      treatment. CONCLUSIONS: Overall, the providers responded that SMBP could be
      useful to them in managing hypertension but seem hesitant to endorse it fully at
      this time, possibly anticipating potential problems that could arise with SMBP
      use. Physicians with more patients using self-monitoring were more likely to
      endorse it.

PMID- 14688556
TI  - Validation of the TONOPORT V ambulatory blood pressure monitor according to the
      European Society of Hypertension International Protocol for Validation of Blood
      Pressure Measuring Devices in Adults.
AB  - BACKGROUND: It is now accepted that blood pressure measuring devices should be
      subjected to an independent evaluation of their accuracy before they are marketed
      for clinical use. The results of validation of the TONOPORT V blood pressure
      monitor for the measurement of ambulatory blood pressure according to the
      European Society of Hypertension International Protocol for Validation of Blood
      Pressure Measuring Devices in Adults are presented in this paper. POPULATION:
      Thirty-three subjects were recruited from among staff and patients at Beaumont
      Hospital, Dublin, Ireland. METHODS: The TONOPORT V monitor was connected to the
      Sphygmocorder, an audiovisual system for validation, which records blood pressure
      on tape and video for later analysis. Nine sequential same-arm measurements
      between the device and a standard mercury sphygmomanometer were recorded using
      the Sphygmocorder. RESULTS: In phase 1, the TONOPORT V monitor produced 28
      measurements within 5 mmHg, 37 within 10 mmHg and 40 within 15 mmHg for systolic
      blood pressure (SBP), and 26 within 5 mmHg, 38 within 10 mmHg and 44 within 15
      mmHg for diastolic blood pressure (DBP). The mean differences were -2.2 (8.6)
      [mean (SD)] mmHg for SBP and +0.5 (7.2) mmHg for DBP. The TONOPORT V monitor
      passed all the criteria for both SBP and DBP. In phase 2.1, the TONOPORT V
      monitor had 56 measurements within 5 mmHg, 78 within 10 mmHg and 88 within 15
      mmHg for SBP, and 60 measurements within 5 mmHg, 83 within 10 mmHg and 97 within
      15 mmHg for DBP. The mean differences were -1.4 (8.7) mmHg for SBP and -0.2 (6.8)
      mmHg for DBP. The TONOPORT V monitor passed the criteria for DBP but failed to
      meet any of the criteria for SBP. In phase 2.2, 19 subjects had at least two of
      the differences within 5 mmHg and six subjects had no differences within 5 mmHg
      for SBP, and 22 subjects had at least two of the differences within 5 mmHg and
      six subjects no differences within 5 mmHg for DBP. The TONOPORT V monitor failed
      to meet the criteria for SBP and for DBP. CONCLUSIONS: The TONOPORT V monitor
      cannot be recommended for clinical use in an adult population because it records
      SBP inaccurately and because it records DBP inaccurately in an unacceptably high
      proportion of people.

PMID- 14688557
TI  - Validation of the ROSSMAX blood pressure measuring monitor according to the
      European Society of Hypertension International Protocol for Validation of Blood
      Pressure Measuring Devices in Adults.
AB  - BACKGROUND: It is now accepted that blood pressure measuring devices should be
      subjected to an independent evaluation of their accuracy before they are marketed
      for clinical use. The results of validation of the ROSSMAX Blood Pressure
      Measuring Monitor for self-measurement according to the European Society of
      Hypertension International Protocol for Validation of Blood Pressure Measuring
      Devices in Adults are presented in this paper. POPULATION: Thirty-three subjects
      were recruited from among staff and patients at Beaumont Hospital, Dublin,
      Ireland. METHODS: The ROSSMAX monitor was connected to the Sphygmocorder, an
      audiovisual system for validation, which records blood pressure on tape and video
      for later analysis. Nine sequential same-arm measurements between the device and
      a standard mercury sphygmomanometer were recorded using the Sphygmocorder.
      RESULTS: In phase 1, the ROSSMAX monitor produced 21 measurements within 5 mmHg,
      31 within 10 mmHg and 38 within 15 mmHg for systolic blood pressure (SBP), and 36
      within 5 mmHg, 43 within 10 mmHg and 45 within 15 mmHg for diastolic blood
      pressure (DBP). The mean differences were -5.6 (10.2) [mean (SD)] mmHg for SBP
      and -0.5 (4.5) mmHg for DBP. The ROSSMAX monitor failed to meet any of the
      criteria for SBP but comfortably passed all of the criteria for DBP. In phase
      2.1, the ROSSMAX monitor had 51 measurements within 5 mmHg, 73 within 10 mmHg and
      86 within 15 mmHg for SBP, and 71 measurements within 5 mmHg, 93 within 10 mmHg
      and 98 within 15 mmHg for DBP. The mean differences were -4.5. (9.5) mmHg for SBP
      and -1.8 (5.0) mmHg for DBP. The ROSSMAX monitor failed to meet any of the
      criteria for SBP but comfortably passed all of the criteria for DBP. In phase
      2.2, 16 subjects had at least two of the differences lying within 5 mmHg and 10
      subjects had no differences within 5 mmHg for SBP; 26 subjects had at least two
      of the differences falling within 5 mmHg and three subjects no differences within
      5 mmHg for DBP. The ROSSMAX monitor failed to meet the criteria for SBP but
      passed the criteria for DBP. CONCLUSIONS: The ROSSMAX monitor cannot be
      recommended for clinical use in an adult population because it records SBP
      inaccurately.

PMID- 14688558
TI  - Ambulatory blood pressure monitoring: is the daytime period enough for making
      clinical decisions?
AB  - AIM: To assess the agreement between the clinical information provided by the
      ambulatory daytime average and 24 h average blood pressure value for diagnosing
      hypertension and assessing the effects of antihypertensive treatment. METHODS: We
      analysed 261 24 h ambulatory monitoring records (SpaceLabs 90207, SpaceLabs,
      Redmond, Washington, USA) obtained from hypertensives over 18 years of age (mean
      age 55.8 years) in order to make a diagnosis of hypertension or assess its
      control in response to treatment. Recording was programmed to occur every 20 min
      during waking periods and every 30 min during sleep, daily activity also being
      registered. The criteria compared in the diagnosis of hypertension were: (1) the
      evaluation criterion: an average blood pressure for the activity period of less
      than 135/85 mmHg (Joint National Committee VI); (2) the gold standard: an average
      blood pressure over 24 h of less than 125/80 mmHg (World Health Organization
      International Society of Hypertension, 1999). RESULTS: In 90% of the records,
      there was agreement between both criteria. In 7.2%, the awake blood pressure
      average was normal and the 24 h average high. Values obtained were: sensitivity,
      89% (95% confidence interval 84-89%); specificity, 92% (95% CI 88-95%); positive
      predictive value, 95.6% (95% CI 93-98%); negative predictive value, 81% (95% CI
      75-85%); pretest probability, 66% (95% CI 60-72%); positive likelihood ratio, 11;
      and negative likelihood ratio, 0.3. There were no significant differences in age,
      gender or percentage of treated subjects between the groups with and without
      agreement. CONCLUSIONS: Daytime and 24 h average blood pressure may indeed carry
      similar information for diagnosing hypertension and assessing the effects of
      antihypertensive treatment in clinical practice. Ambulatory blood pressure
      monitoring used only during the daytime period could be better tolerated and
      agreed to by patients than 24 h monitoring.

PMID- 14688560
TI  - Growth, survival and viral load in symptomatic childhood human immunodeficiency
      virus infection.
AB  - BACKGROUND: The relationships among weight and height growth, viral load and
      survival in HIV-infected children remain unclear. OBJECTIVES: To determine
      whether weight or height growth velocity independently predicts survival and to
      investigate associations of weight, height and head circumference growth
      velocities with viral loads in symptomatic HIV-infected children. METHODS: We
      analyzed data from a prospective antiretroviral study utilizing clinical
      endpoints (PACTG 152). Viral load [log(RNA PCR)] and anthropometric measures 12
      weeks before and after viral load measures were available in 494 of 831 children.
      Interval changes during 24 weeks in z-scores for weight-for-age (DeltaWAZ),
      height-for-age (DeltaHAZ) and head circumference-for-age (DeltaHCZ) were used as
      growth velocity surrogates. Logistic regression determined whether DeltaWAZ
      and/or DeltaHAZ correlated with survival when age, viral load and CD4+ cell count
      were controlled. Bivariate analysis assessed correlation among viral load and
      DeltaWAZ, DeltaHAZ and/or DeltaHCZ. RESULTS: Survival related significantly to
      height growth velocity (P = 0.03, n = 434) but not to weight growth velocity (P =
      0.84, n = 446) or head circumference growth velocity (P = 0.67, n = 148). Viral
      load was not significantly associated with changes in weight-, height-, or head
      circumference-for-age z scores (P = 0.86, n = 235; P = 0.07, n = 226; and P =
      0.09, n = 165, respectively) in children <30 months of age or with changes in
      weight- or height-for-age z scores (P = 0.27, n = 259; P = 0.11, n = 251) in
      older children. CONCLUSIONS: Height growth velocity predicted survival
      independently of age, viral load and CD4+ cell count. Weight, height and head
      circumference growth velocities were not significantly associated with viral load
      in symptomatic HIV-infected children in this large prospective trial of
      nucleoside reverse transcriptase therapy.

PMID- 14688561
TI  - Aseptic meningitis in infants younger than six months of age hospitalized with
      urinary tract infections.
AB  - BACKGROUND: Aseptic meningitis associated with urinary tract infection (UTI) in
      young infants has not been described in detail in the literature. We performed a
      retrospective study to determine the incidence and clinical features of aseptic
      meningitis accompanying UTI. METHODS: We retrospectively reviewed the medical
      records of all infants younger than 6 months of age hospitalized with a UTI at
      Miller Children's Hospital from March 1995 through March 2000. UTI was defined as
      a urine culture growing > or =10,000 colony-forming units/ml of a single organism
      from a catheterized specimen or > or =100,000 colony-forming units/ml of a single
      organism from a bagged urine specimen. Meningitis was defined as a positive
      cerebrospinal fluid culture or cerebrospinal fluid with >35 white blood cells/mm3
      in infants < or =30 days of age or with >10 white blood cells/mm3 in infants >30
      days of age. RESULTS: Of 386 infants with UTI, a lumbar puncture was performed in
      260, and 31 (11.9%) had aseptic meningitis. One infant had bacterial meningitis.
      None of the 26 infants with UTI and bacteremia had aseptic meningitis. Two
      infants with meningitis had confirmed enteroviral infections, but aseptic
      meningitis did not occur more frequently in any particular month or during times
      of peak enteroviral activity. CONCLUSIONS: A cerebrospinal fluid pleocytosis is
      relatively common in hospitalized infants <6 months of age who have a UTI and
      usually does not reflect bacterial meningitis. Knowledge of this may prevent
      unnecessary courses of antibiotics for presumed bacterial meningitis and lead to
      evaluation for other possible causes of aseptic meningitis including viral or
      congenital infections.

PMID- 14688562
TI  - Improving diagnostic testing and reducing overuse of antibiotics for children
      with pharyngitis: a useful role for the electronic medical record.
AB  - BACKGROUND: Because of rising resistance to antibiotics, appropriate use of
      antibiotics is an important measure of quality of care. The purpose of this study
      was to use an electronic medical record (EMR) to assess use of diagnostic testing
      and of antibiotics for pharyngitis in a pediatric outpatient setting and to
      target areas for improvement. METHODS: Using data retrieved from the EMR, we
      analyzed visits from March 1, 2001 to February 28, 2002 for children 3 to 18
      years old diagnosed with pharyngitis. We determined the proportion of episodes
      with a diagnostic test for group A streptococci, the proportion for which a
      prescription for an antibiotic was dispensed and factors that predicted
      prescribing and testing. RESULTS: Of 391 episodes of pharyngitis, a test was
      ordered for 303 (78%). Antibiotics were prescribed for 90 (23%); for 76 of 90
      (84%) a test was ordered. Clinicians were less likely to order tests late in the
      week [relative risk (RR), 0.76; 95% confidence interval (CI), 0.66, 0.87)], more
      likely to order tests for patients with an exudate (RR 1.2; 95% CI 1.1, 1.3) and
      more likely to prescribe an antibiotic for patients with an exudate (RR 1.5; 95%
      CI 1.1, 2.1). When prescribing an antibiotic clinicians were less likely to order
      tests late in the week (RR 0.1; 95% CI 0.02, 0.5) and for patients diagnosed with
      scarlet fever (RR 0.07; 95% CI 0.01, 0.4). CONCLUSION: Using data from the EMR,
      we could assess adherence to the guidelines for antibiotic use and identify areas
      to target for improving diagnostic testing and reducing overuse of antibiotics in
      our clinic.

PMID- 14688563
TI  - Infective endocarditis in Arkansan children from 1990 through 2002.
AB  - BACKGROUND: Recent medical and surgical advances have increased the potential
      risk of endocarditis. Epidemiology, pathogens, morbidity and/or mortality may
      have evolved in the past decade in pediatric patients diagnosed with
      endocarditis. METHODS: Retrospective reviews of medical records from Arkansas
      Children's Hospital were done to identify patients with infective endocarditis
      from January 1990 through December 2002. Basic demographic and clinical data were
      gathered and reviewed. RESULTS: Of 76 patients identified, 57 were included based
      on diagnostic criteria. Congenital heart disease with (56%) and without (25%)
      correction were the most common risk factors. Echocardiograms revealed
      vegetations in 67%. Echocardiograms remain relatively deficient in patients with
      complex cyanotic heart disease (50% positive) vs. those with normal anatomy (83%
      positive). Streptococci (30%) and Staphylococcus aureus (21%) were the most
      common organisms identified overall; however, we observed a predominance of
      enterococci in infants <2 years of age (41%). Our study revealed a reduced rate
      of complications, especially of the central nervous system (7% vs. 25 and 33% in
      prior studies); however, our rate of S. aureus was lower (21% vs. 32 and 39%),
      and this pathogen continues to be associated with a higher incidence of
      complications. CONCLUSIONS: Infective endocarditis continues to present a
      difficult challenge in pediatrics; its associated pathogens and outcomes have
      changed little in the past decade.

PMID- 14688564
TI  - Utility of sepsis evaluation in infants 90 days of age or younger with fever and
      clinical bronchiolitis.
AB  - OBJECTIVE: To identify the clinical utility of obtaining blood, urine and
      cerebrospinal fluid for bacterial culture among febrile infants <90 days of age
      with clinical bronchiolitis. DESIGN: Retrospective chart review from 1995 to
      2000. SETTING: Urban emergency department of a tertiary children's hospital.
      PARTICIPANTS: All infants <90 days of age presenting with fever and clinical
      bronchiolitis. MAIN OUTCOME MEASURES: Result of the cultures of blood, urine and
      cerebrospinal fluid. RESULTS: Of 3051 (11%) febrile infants, 329 met criteria for
      clinical bronchiolitis. Blood for culture was obtained from 309 (94%), urine for
      culture was obtained from 273 (83%) and cerebrospinal fluid for culture was
      obtained from 200 (61%). One hundred eighty-seven (57%) infants had all 3
      specimens sent for culture. No cases of bacteremia [0%; 95% confidence interval
      (CI), 0, 1.1%] or meningitis (0%; 95% CI 0, 1.8%) occurred among these infants.
      However, 6 infants (2%; 95% CI 0.8, 5.7%), all male, had a culture of urine
      consistent with infection (4 Escherichia coli, 1 Staphylococcus aureus, 1
      viridans streptococci). CONCLUSION: The risk of bacteremia or meningitis among
      infants <90 days with fever and bronchiolitis is low in this age group. The risk
      of urinary tract infection in this age group is also low, but not negligible, at
      2%.

PMID- 14688565
TI  - Childhood malaria in a region of unstable transmission and high human
      immunodeficiency virus prevalence.
AB  - BACKGROUND: Malaria and HIV are important pediatric problems in sub-Saharan
      Africa. It is uncertain how HIV-related immunosuppression and malaria interact in
      children. We aimed to describe associations among HIV status, presentation and
      outcome from malaria in children from Hlabisa district, KwaZulu-Natal, South
      Africa, a region of high HIV prevalence and unstable Plasmodium falciparum
      transmission. METHODS: Consecutive febrile children were screened for malaria
      with a rapid antigen test. After consent was given, clinical data were recorded,
      and blood spots were obtained for HIV antibody testing. Cases were managed
      according to national guidelines. RESULTS: Malaria was diagnosed in 663 children,
      of whom 10.1% were HIV antibody-positive. Semiquantitative asexual and sexual
      stage parasitemia densities were unrelated to HIV status. Overall 161 children
      were hospitalized; 19 (12%) were <1 year old; and 41 (25%) had severe/complicated
      malaria. Severe disease presented more frequently in HIV antibody-positive than
      in HIV-uninfected children (P = 0.05), particularly in those >1 year old with
      coma (P = 0.02) and hypoglycemia (P = 0.05). Receiving parenteral antibiotics was
      associated with severe disease (odds ratio, 3.0; 95% confidence interval, 1.3 to
      6.7) whereas a low white blood cell count (<4 x 10(6)/l) was associated with
      nonsevere disease (odds ratio, 0.4; 95% confidence interval, 0.2 to 0.8). Seven
      children (4.3%) died. Coma, age <1 year and low white blood cell count were the
      clearest predictors of poor outcome. CONCLUSION: HIV infection was associated
      with severe/complicated malaria, although the magnitude of the effect may be
      relatively small. Given that both malaria and HIV are widespread in Africa, even
      small effects may generate significant morbidity and mortality and major public
      health consequences.

PMID- 14688566
TI  - Microbiology of otitis media in Costa Rican children, 1999 through 2001.
AB  - BACKGROUND: Because of the increasing number of resistant middle ear pathogens
      and the impact of the new conjugate Streptococcus pneumoniae vaccine, an active
      surveillance of the microbiology and susceptibility pattern of middle ear
      pathogens is required. OBJECTIVE: To study the microbiology and susceptibility
      pattern of middle ear pathogens obtained from Costa Rican children with acute
      otitis media (AOM), recurrent otitis media (ROM) and therapeutic failure otitis
      media (FOM). METHODS: Between 1999 and 2001 middle ear fluid (MEF) was collected
      from 276 Costa Rican patients. S. pneumoniae serotyping and pulsed field gel
      electrophoresis analysis was done on available strains. RESULTS: Among the total
      study population, 102 were AOM patients, 98 were ROM patients and 76 were FOM
      patients. Overall S. pneumoniae (88 strains) was the most common pathogen
      isolated followed by Haemophilus influenzae (41 strains) and Streptococcus
      pyogenes (10 strains). H. influenzae was the most common agent in FOM patients (P
      = 0.015). Beta-lactamase production was observed in 3 of 41 (7%) H. influenzae
      strains and 3 of 3 (100%) Moraxella catarrhalis strains. Penicillin
      nonsusceptible S. pneumoniae strains were more common in FOM (64%) and ROM (63%)
      patients than in AOM (42%) patients (P = 0.05). S. pneumoniae serotype 19F was
      the most prevalent serotype, mainly within one distinct clone. CONCLUSIONS:
      Overall S. pneumoniae serotype 19F was the most common isolate from the middle
      ear fluid of Costa Rican children. Beta-lactamase-negative H. influenzae was the
      most prevalent in the subpopulation of patients with FOM. S. pyogenes was the
      third most common isolate and M. catarrhalis was uncommon.

PMID- 14688567
TI  - Invasive pneumococcal disease in Costa Rican children: a seven year survey.
AB  - BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive bacterial
      disease in children worldwide. Although morbidity and mortality associated with
      invasive pneumococcal disease (IPD) are known to be high in Latin American
      infants, the current situation for Central American children is unclear. METHODS:
      A 7-year retrospective review of IPD cases (January 1995 to December 2001)
      treated at the National Children's Hospital in San Jose, Costa Rica. RESULTS: We
      analyzed 135 episodes that occurred in 132 patients. The mean age of presentation
      was 35.7 months (range, 0 to 11.4 ys), with 73.3% of all episodes occurring in
      patients <5 years of age and 56% occurring in patients <24 months of age.
      Underlying medical conditions were present in 47% of children. The most common
      clinical presentations were meningitis in 56 (41.5%) patients, pneumonia in 36
      (26.7%), bacteremia alone in 30 (22.2%), peritonitis in 10 (7.4%), septic
      arthritis in 2 (1.5%) and osteomyelitis in 1 (0.7%). The case fatality rate was
      14.4%, and children <2 years of age had the highest rates of complications,
      sequelae and death. Penicillin or cefotaxime nonsusceptibility was observed in
      14.3% (10.7% intermediate, 3.6% resistant) and 4.5% (1.5% intermediate, 3%
      resistant) of tested isolates, respectively. CONCLUSIONS: IPD in Costa Rica is
      associated with high morbidity and mortality, particularly among young infants.
      Most prevalent IPD are the ones observed in developed countries before the
      introduction of current conjugated vaccine. Penicillin and third generation
      cephalosporin resistance in invasive cases is present at low rates.

PMID- 14688568
TI  - Penicillin concentrations in sera and tonsils after intramuscular administration
      of benzathine penicillin G to children.
AB  - BACKGROUND: The optimal regimen of benzathine penicillin G for secondary
      prevention of rheumatic fever is controversial. Data from serum pharmacokinetic
      studies do not fully agree on the period of protection after drug administration.
      Data from concentration of penicillin in tonsils may provide additional
      information. METHODS: To evaluate penicillin concentrations in palatine tonsils
      and in sera 1, 10, 14 and 21 days after intramuscular injection of benzathine
      penicillin G 40,000 IU/kg, 58 children between 4 and 12 years of age with chronic
      tonsillitis and indication for tonsillectomy were given the study drug 1, 10, 14
      or 21 days before surgery. Blood and tonsil samples were obtained during surgery,
      and penicillin concentrations were determined microbiologically by the agar well
      diffusion technique. RESULTS: Mean serum penicillin concentrations 1, 10, 14 and
      21 days after drug administration were, respectively, 0.080, 0.031, 0.023 and
      0.014 microg/ml. Mean penicillin concentrations in tonsils at 1, 10, 14 and 21
      days were 0.023, 0.010, 0.007 and 0.002 microg/g, respectively. Detectable
      penicillin concentration in tonsils (method sensitivity, 0.006 microg/g) was
      obtained in all patients on Day 1 and in 91% and 83.3% of patients on Days 10 and
      14, respectively. By Day 21 this proportion was reduced to 30%. CONCLUSIONS: The
      results of this study suggest that penicillin values may be inadequate for
      prevention of rheumatic fever by Week 3 of administration in a majority of
      children.

PMID- 14688569
TI  - Causes of febrile illnesses after a tick bite in Slovenian children.
AB  - BACKGROUND: To establish the etiology in Slovenian children with febrile
      illnesses occurring after a tick bite. METHODS: Eighty-six febrile patients
      younger than 15 years referred to our institution in 2001 with a history of a
      tick bite within 6 weeks before onset of the illness were included in this
      prospective study. Acute and convalescent serum samples were tested for the
      presence of antibodies to tick-borne encephalitis virus, Borrelia burgdorferi
      sensu lato, Anaplasma phagocytophilum, Ehrlichia chaffeensis, Rickettsia conorii,
      Babesia microti, Bartonella henselae, Bartonella quintana and Francisella
      tularensis. Cerebrospinal fluid was investigated in patients in whom meningeal
      involvement was clinically suspected. Blood and/or cerebrospinal fluid from the
      patients were cultured in modified Kelly-Pettenkofer medium. PCR was performed to
      detect ribosomal DNA of A. phagocytophilum and E. chaffeensis. RESULTS: Of 86
      patients 33 (38%) were excluded because a well-defined febrile illness not
      associated with tick bite was established. Tick-borne illness was diagnosed in 28
      (53%) of the 53 remaining patients. The most common diagnosis was tick-borne
      encephalitis (64%), followed by Lyme borreliosis (46%), human monocytic
      ehrlichiosis and human granulocytic ehrlichiosis (serologic evidence of infection
      in 9 and 4%, respectively). In 6 (21%) patients there was evidence for infection
      with more than 1 tick-borne agent. CONCLUSIONS: Tick-borne illness was
      established in 53% of the patients younger than 15 years presenting with febrile
      illness occurring within 6 weeks after a tick bite. The most common identified
      illnesses were tick-borne encephalitis and Lyme borreliosis.

PMID- 14688570
TI  - Human immunodeficiency virus protease inhibitors.

PMID- 14688571
TI  - Impact of intrapartum chemoprophylaxis on neonatal sepsis.

PMID- 14688572
TI  - A ten-year-old boy with a pulmonary nodule secondary to Cryptococcus neoformans:
      case report and review of the literature.
AB  - Pulmonary cryptococcosis is an uncommonly recognized disease of childhood. Among
      immunocompetent and non-HIV-infected individuals, pulmonary cryptococcosis may be
      asymptomatic or present with chronic, nondescript symptomatology. In this report
      we describe a 10-year-old with malignant fibrous histiocytoma of bone and a
      pulmonary nodule secondary to Cryptococcus neoformans. We use this case as a
      background to review the pediatric literature regarding pulmonary cryptococcosis
      and to discuss the utility of immunohistochemistry for diagnosis of this clinical
      entity.

PMID- 14688573
TI  - A case of severe monkeypox virus disease in an American child: emerging
      infections and changing professional values.
AB  - Monkeypox virus disease is a rare zoonosis that until recently was limited to
      Central Africa. We describe the clinical features of the third child in the
      United States reported with this newly emerging infection. This child was part of
      a large cluster of individuals in the Midwest infected by prairie dogs that had
      contracted the virus when housed with infected small mammals imported from
      Africa. The differential and laboratory diagnoses and the difficulty finding
      physicians and nurses to care for this patient are discussed.

PMID- 14688575
TI  - Clinical presentation of parvovirus B19 infection in children with aplastic
      crisis.
AB  - The records of 22 children with parvovirus B19-induced aplastic crisis were
      reviewed. The group consisted of 16 children with sickle cell hemoglobinopathies
      and 6 with hereditary spherocytosis. Children presented to the hospital 0.5 to 8
      days (mean, 2.4 days) after the onset of symptoms. The children with sickle-cell
      disease presented earlier (mean, 1.4 days) than did children with hereditary
      spherocytosis (mean, 5 days; P = 0.02. Fever was the most common symptom,
      occurring in 73% of children. Rash did not occur in either group. Reticulocyte
      counts began to rise 1 week after onset of illness associated with a rise in
      parvovirus B19-specific IgG antibody. These data suggest that parvovirus B19
      infection in children with sickle-cell hemoglobinopathies and heredity
      spherocytosis differs from infection in normal children.

PMID- 14688576
TI  - Vancomycin-resistant Enterococcus faecium endocarditis in a premature infant
      successfully treated with linezolid.
AB  - A 4 1/2-month-old, 26-week premature infant with multiple complications of
      prematurity required a central venous catheter for venous access and antibiotic
      treatment of bacterial nosocomial infections. He developed tricuspid valve
      endocarditis with vegetation caused by Enterococcus faecium resistant to
      ampicillin, vancomycin and quinupristin-dalfopristin but susceptible to
      linezolid. He was successfully treated with linezolid intravenously (7 weeks) and
      then orally (2 weeks).

PMID- 14688577
TI  - Acute nephritis and respiratory tract infection caused by Mycoplasma pneumoniae:
      case report and review of the literature.
AB  - A 6-year-old boy presented with an acute infection caused by Mycoplasma
      pneumoniae associated with respiratory tract and kidney involvement. Renal
      manifestations included acute nephritis with decreased C3 fraction of serum
      complement, occurring concomitantly with the respiratory symptoms. The child had
      an excellent outcome, with rapid normalization of C3 and complete resolution of
      the acute nephritis.

PMID- 14688578
TI  - Macrophage infiltration of pancreatic acini and islets in acute Kawasaki disease.
AB  - A report of 2 patients who developed diabetes after Kawasaki disease (KD) led us
      to determine whether macrophages and/or T cells infiltrate acute KD pancreas.
      Three of 10 acute fatal KD cases had diffuse macrophage infiltration of the
      pancreas; T cells were not prominent. Affected islets were seen in close
      proximity to normal islets. These findings may explain the rarity of diabetes
      after KD.

PMID- 14688579
TI  - Mycobacterium aurum bacteremia in an immunocompromised child.
AB  - Mycobacterium aurum was cultured from the Broviac catheter of a 5-year-old child
      with metastatic Wilms tumor. Removal of the catheter resulted in prompt
      resolution of the fever and sterilization of the blood culture. This rapidly
      growing mycobacterium, previously believed to be a commensal, can cause disease
      in the immunocompromised host.

PMID- 14688580
TI  - Case report: Invasive aspergillosis successfully treated with voriconazole
      without recurrence during subsequent bone marrow transplantation.
AB  - Invasive aspergillosis is an important cause of morbidity and mortality among
      immunosuppressed oncology patients. We report a 17-year-old patient with a T cell
      acute lymphocytic leukemia and invasive aspergillosis treated with voriconazole
      who remained infection-free during bone marrow transplant.

PMID- 14688581
TI  - Are Gilbert's syndrome and liver involvement genetically linked in infectious
      mononucleosis?

PMID- 14688584
TI  - The march toward rational therapeutics in children.
AB  - Although children suffer from many of the same diseases as adults, the majority
      of drugs are not approved for pediatric use. This places children at risk, either
      that they will not be treated adequately because of the lack of approved agents
      or that their physician will be lacking the necessary labeling information to
      treat appropriately with a given agent. This paper details the slow progress over
      the last 25 years toward providing pediatric labeling and thus providing children
      with optimal protection and range of treatment options.

PMID- 14688585
TI  - Pediatric clinical trial experience: government, child, parent and physician's
      perspective.
AB  - In contrast to investigations in adults, investigation of drugs via clinical
      trials has been lacking in the pediatric population. Until recently there was
      little incentive on the part of the pharmaceutical industry to conduct clinical
      trials of new drugs in children. However, government legislation approved in the
      late 1990s has promoted efforts to investigate the effects of drugs in the
      treatment of a variety of children's diseases. Such data provide important and
      needed information on appropriate dosing, rates and types of adverse reactions
      and efficacy for treatment of pediatric illnesses. The conduct of clinical trials
      in children is dependent on a careful dialogue between the investigator, child
      and guardians wherein a detailed description of benefits vs. risks is conveyed.
      The focus of this paper is to summarize various perspectives on conducting
      clinical trials in children, including those of the government, the child, the
      parents or guardians and the investigator. Although children now have access to
      new medicines during the development process, their participation in clinical
      trials must still protect them from undue risk and secure their well being.

PMID- 14688586
TI  - Safety profile of quinolone antibiotics in the pediatric population.
AB  - Fluoroquinolone-induced joint/cartilage toxicity has been observed in juvenile
      animal studies and is species- and dose-specific with canines exhibiting the
      highest rate of arthralgias. These early observations led to the contraindication
      of fluoroquinolones in the pediatric population. Despite these recommendations
      fluoroquinolones continue to be prescribed for select children with difficult-to
      treat infections for whom the benefit of quinolone therapy may outweigh the risk
      of cartilage toxicity. A review of retrospective and prospective safety data of
      ciprofloxacin-treated children showed that the rates of arthralgia and quinolone
      induced cartilage toxicity were low. Episodes of arthralgia were mostly
      reversible based on published surveillance data in children. Recent data from
      Bayer's ciprofloxacin clinical trials database found that the incidence of
      arthralgia in children did not differ between the ciprofloxacin and nonquinolone
      antimicrobial control groups. The role of fluoroquinolones in the treatment of
      certain serious infections in children does not appear to be compromised by
      safety concerns when used appropriately.

PMID- 14688587
TI  - Pediatric urinary tract infections: the role of fluoroquinolones.
AB  - Infections of the urinary tract (UTI) occur commonly in the pediatric population.
      Because of the high association of pediatric UTI with congenital structural
      anomalies of the urinary tract and with dysfunctional elimination syndromes, it
      is far more common for children to be categorized as having complicated UTI than
      their adult counterparts. And for children more intensive therapy is often
      required. Early and effective treatment of UTIs in the pediatric patient is
      considered essential to prevent long term morbidity and potential mortality from
      end stage renal disease. An oral antimicrobial is more convenient than parenteral
      therapy and is preferable as long as clinical efficacy and safety can be assured.
      Oral fluoroquinolones are an attractive alternative for the treatment of
      complicated UTI in children, and safety must always be a factor in considering
      their use in this population. Although the role of fluoroquinolones in pediatric
      UTI is still under investigation, the limited data available demonstrate a
      likelihood of efficacy and safety.

PMID- 14688588
TI  - Ciprofloxacin in treatment of fever and neutropenia in pediatric cancer patients.
AB  - This article reviews clinical trials of outpatient management of fever and
      neutropenia in pediatric cancer patients. The syndrome of fever and neutropenia
      is discussed, and strategies of identifying patients at low risk for complex or
      fatal infections are described. A number of clinical trials in a wide range of
      clinical settings and countries have demonstrated that low risk pediatric cancer
      patients with fever and neutropenia can be prospectively identified and safely
      treated as outpatients. In addition outpatient management has been shown to be
      less costly than conventional intravenous therapy in hospitalized patients. Oral
      fluoroquinolones, including ciprofloxacin, have been used as a component of
      therapy in several trials because of their ease of administration and their
      activity against the majority of pathogenic bacteria causing illness in this
      group. The article also discusses the role of antibiotic prophylaxis of fever and
      neutropenia in certain high risk settings, such as hematopoietic stem cell
      transplantation. In selected high risk patients, prophylactic use of limited
      spectrum fluoroquinolones such as ciprofloxacin may reduce the incidence of Gram
      negative bacteremias. Use of fluoroquinolone therapy as prophylaxis, however, is
      controversial because of concerns about an emergence of resistant organisms.
      Prudent use of fluoroquinolones as therapy and prophylaxis is essential to
      prolonging the benefits of this class of compounds.

PMID- 14688589
TI  - Appropriate antibiotic use and why it is important: the challenges of bacterial
      resistance.
AB  - After the introduction of antibiotics in the mid-20th century, clinicians soon
      witnessed clinical failures secondary to bacterial resistance. Despite
      scientists' efforts to synthesize more potent antibiotics during the last five
      decades, bacterial resistance continues to evolve, in large part because of the
      overuse and misuse of antibiotics. The treatment of several pathogens, including
      methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus
      pneumoniae and vancomycin-resistant enterococci, is problematic. New solutions
      are needed to preserve the activity of our current antibiotic armamentarium, to
      lower the overall risk of bacterial resistance and to successfully treat patients
      with resistant bacterial infections. Options include: development of new
      antibiotics to treat resistant organisms; vaccination to prevent infections; and
      improved use of antibiotics. Because bacteria will eventually develop means to
      avoid being killed by antibiotics, judicious use of antibiotics by all clinicians
      is imperative. Appropriate antibiotic use involves selection of a "targeted
      spectrum" antibiotic, as well as an appropriate dose and duration.

PMID- 14688590
TI  - Patterns of papillary muscle ischemia in myocardial PET.
AB  - PURPOSE: Conventional nuclear medicine equipment lacks sufficient spatial
      resolution to reliably visualize the papillary muscles (PM). Positron emission
      tomography (PET), however, can adequately visualize these structures using
      various positron emitters. METHODS AND PATIENTS: We present various patterns of
      PM observed on myocardial PET imaging in 4 patients. These patterns demonstrate
      different pathologic conditions such as PM ischemia of varying severity, as well
      as hibernation, using both N-13 NH3 and F-18 FDG as perfusion and metabolic
      agents, respectively. These patterns of infarction, stress-induced myocardial
      ischemia, or hibernation can be identified in one or both PM using PET scanning.
      Normal PM visualization on chest F-18 FDG PET images is also presented.
      CONCLUSION: This report illustrates the potential ability of myocardial PET as a
      noninvasive modality to study the perfusion and metabolic abnormalities of the
      PM.

PMID- 14688591
TI  - Positron emission tomography/computed tomography fusion imaging in brown adipose
      tissue.
AB  - Fluorine-18 fluoro deoxyglucose positron emission tomography (F-18 FDG PET)
      imaging is an exciting modality for the study of pathophysiology. The fusion of
      computed tomography (CT) anatomic data to metabolic F-18 FDG PET data allows
      accurate mapping of the metabolic activity of the body. With each patient
      evaluated with fusion PET/CT imaging, valuable information is obtained regarding
      anatomic and physiological abnormalities and normal variants. We describe 4 cases
      in which the unusual distribution of increased FDG metabolism localized to fat,
      which we propose represents brown adipose tissue. The accurate anatomic
      localization of this hypermetabolic fat is aided by imaging these patients on a
      combined PET/CT system.

PMID- 14688592
TI  - Bone scintiscanning in osteolytic lesions.
AB  - Osteolytic lesions seen on plain radiographs can be caused by various disorders
      of the bones such as simple bone cyst, aneurysmal bone cyst, plasmacytoma, giant
      cell tumor, eosinophilic granuloma and tuberculosis. We studied prospectively Tc
      99m-methylene diphosphonate bone scan findings in osteolytic lesions seen
      radiologically and followed them to histopathology. Interestingly, the scans in
      these patients helped to show if the lesions were monoostotic or polyostotic and,
      in some cases, ruled out malignant or infective etiology.

PMID- 14688593
TI  - Can thallium-pertechnetate subtraction scanning play a role in the preoperative
      imaging for minimally invasive parathyroidectomy?
AB  - PURPOSE: Preoperative Tc-99m sestamibi scanning can identify candidates for
      minimally invasive parathyroid surgery. However, a significant number of patients
      with single gland disease have negative scans and are not considered for the
      minimally invasive procedure. MATERIALS AND METHODS: To determine if T1-201/Tc
      99m sodium pertechnetate subtraction scanning (TPSS) is a viable alternative
      imaging technique for patients with primary hyperparathyroidism (1 degrees HPTH),
      we reviewed our experience. The outcomes of 100 consecutive patients with 1
      degrees HPTH who underwent preoperative TPSS and parathyroid exploration between
      1995 and 2000 at our institution were retrospectively reviewed. RESULTS: The mean
      preoperative calcium and parathyroid hormone levels were 10.8 mg/dL and 220
      pg/mL, respectively. The overall cure rate was 96%. Single gland disease was
      present in 88%. Of the 100 patients studied, 15 underwent both a Tc-99m sestamibi
      scan and TPSS, whereas the other 85 had only the TPSS. CONCLUSIONS: The
      sensitivity and positive predictive value of the TPSS were 73.3% and 90.4%,
      respectively. In the patients undergoing both TPSS and Tc-99m sestamibi scans,
      the results concurred in 60%. However, in 20% of the remaining patients, TPSS
      correctly localized the abnormal parathyroid(s) when Tc-99m sestamibi failed.
      TPSS has a comparable sensitivity and positive predictive value to Tc-99m
      sestamibi scanning. In patients with a negative Tc-99m sestamibi scan, TPSS can
      provide additional localizing information. As a result of the high positive
      predictive value of TPSS, a single parathyroid gland localized by TPSS alone can
      then be approached by minimally invasive parathyroidectomy.

PMID- 14688594
TI  - Can exercise renography be an alternative to ACE inhibitor renography in
      hypertensive patients who are suspicious for renal artery stenosis?
AB  - The aim of this study was to evaluate the value of Tc-99m ethylenedicysteine
      exercise renography in patients with hypertension who were suspicious for renal
      artery stenosis and compare the results with captopril renography. METHODS:
      Twenty-nine patients with hypertension who were highly suspect for having renal
      artery stenosis were included in the study. Basal captopril exercise renograms
      were performed within 1 week in all patients with Tc-99m EC. Exercise was
      performed with a bicycle ergometer as described in the literature.
      Interpretations of renograms were made according to the consensus report on
      angiotensin converting enzyme (ACE) inhibitor renography as high, low, or
      intermediate probability. The sensitivity, specificity, and positive and negative
      predictive values were also obtained on both the kidneys and a patient basis. The
      results were compared with renal angiography in 19 patients. RESULTS: Twenty of
      29 patients had concordant results with both captopril and exercise studies. All
      discordant tests were normal with captopril but positive with exercise renograms.
      Nineteen patients with 38 kidneys were included for statistical data analysis.
      Nine kidneys, which were either atrophic or abnormal during the basal study, were
      excluded from the kidney-based analysis. With contrast angiography, 8 patients
      had renal artery stenosis. When evaluated on a kidney basis, the sensitivity,
      specificity, and positive and negative predictive values for captopril scans were
      87%, 100%, 100%, and 95%, and for the exercise scans were 100%, 90%, 80%, and
      100% respectively. When calculated on a patient basis with regard to the
      captopril scans, the sensitivity, specificity, and positive and negative
      predictive values were 87%, 81%, 77%, and 88%, and for exercise scans were 100%,
      54%, 61%, and 100% respectively. There were 2 false-positive exercise scans that
      were found to be the result of dilated minor collecting systems and changes in
      kidney contours as a result of motion during exercise. CONCLUSIONS: These results
      indicate that exercise renography has a similar sensitivity but lower specificity
      compared with captopril scintigraphy in the diagnosis of renal artery stenosis.
      Because of the lower specificity, its use in the screening of renovascular
      hypertension may be limited. Exercise renography may be more useful as an
      investigative tool for essential hypertension.

PMID- 14688595
TI  - F-18 fluorodeoxyglucose positron emission tomographic imaging in a patient with
      persistent hiccups.

PMID- 14688596
TI  - Splenic infarction mimicking gastric remnant on PET imaging.

PMID- 14688597
TI  - Fusion positron emission tomography-computed tomography demonstration of epidural
      metastases.

PMID- 14688598
TI  - Stress-induced fracture involving a nonossifying fibroma.

PMID- 14688599
TI  - Bone scan 14 days after a toxic lignocaine reaction.

PMID- 14688600
TI  - Ollier disease with synchronous multicentric chondrosarcomas: scintigraphic and
      radiologic demonstration.

PMID- 14688601
TI  - Mixed form lymphatic malformation of the foot simulating acute soft-tissue lesion
      on 3-phase bone scintigraphy.

PMID- 14688602
TI  - Ga-67 citrate and Tc-99m pertechnetate scintigraphy in thyroid lymphoma.

PMID- 14688603
TI  - Ga-67 citrate scintigraphy in the diagnosis of primary hepatic lymphoma.

PMID- 14688604
TI  - Congenital hepatic fibrosis in a patient with suspected postcholecystectomy
      syndrome: hepatobiliary scintigraphy at diagnosis and during follow-up.

PMID- 14688605
TI  - Multisystemic sarcoidosis with uncommon osseous involvement demonstrated by Ga-67
      citrate and Tc-99m MDP.

PMID- 14688606
TI  - False-positive Tc-99m HMPAO leukocyte scan secondary to adenocarcinoma of the
      ileum.

PMID- 14688607
TI  - Bone scintigraphy in cleidocranial dysplasia.

PMID- 14688608
TI  - Post-traumatic cerebral venous infarct mimicking an infiltrative glioma.

PMID- 14688609
TI  - Incidental detection of atelectasis on Tc-99m MDP bone scans.

PMID- 14688610
TI  - Detection of recurrent skull osteosarcoma by skull single photon emission
      computed tomography using Tc-99m methylene diphosphonate.

PMID- 14688611
TI  - Coupling of changes in cerebral blood flow with neural activity: what must
      initially dip must come back up.
AB  - Activation flow coupling, increases in neuronal activity leading to changes in
      cerebral blood flow (CBF), is the basis of many neuroimaging methods. An early
      rise in deoxygenation, the "initial dip," occurs before changes in CBF and
      cerebral blood volume (CBV) and may provide a better spatial localizer of early
      neuronal activity compared with subsequent increases in CBF. Imaging modality,
      anesthetic, degree of oxygenation, and species can influence the magnitude of
      this initial dip. The observed initial dip may reflect a depletion of
      mitochondrial oxygen (O(2)) buffers caused by increased neuronal activity.
      Changes in CBF mediated by nitric oxide (NO) or other metabolites and not caused
      by a lack of O(2) or energy depletion most likely lead to an increased delivery
      of capillary O(2) in an attempt to maintain intracellular O(2) buffers.

PMID- 14688612
TI  - Subthalamic nucleus stimulation restores glucose metabolism in associative and
      limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced
      Parkinson's disease.
AB  - Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a highly effective
      surgical treatment in patients with advanced Parkinson's disease (PD). Because
      the STN has been shown to represent an important relay station not only in motor
      basal ganglia circuits, the modification of brain areas also involved in non
      motor functioning can be expected by this intervention. To determine the impact
      of STN-DBS upon the regional cerebral metabolic rate of glucose (rCMRGlc), we
      performed positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) in
      eight patients with advanced PD before surgery as well as in the DBS on- and off
      conditions 4 months after electrode implantation and in ten age-matched healthy
      controls. Before surgery, PD patients showed widespread bilateral reductions of
      cortical rCMRGlc versus controls but a hypermetabolic state in the left rostral
      cerebellum. In the STN-DBS on-condition, clusters of significantly increased
      rCMRGlc were found in both lower thalami reaching down to the midbrain area and
      remote from the stimulation site in the right frontal cortex, temporal cortex,
      and parietal cortex, whereas rCMRGlc significantly decreased in the left rostral
      cerebellum. Therefore, STN-DBS was found to suppress cerebellar hypermetabolism
      and to partly restore physiologic glucose consumption in limbic and associative
      projection territories of the basal ganglia. These data suggest an activating
      effect of DBS upon its target structures and confirm a central role of the STN in
      motor as well as associative, limbic, and cerebellar basal ganglia circuits.

PMID- 14688613
TI  - Normal pressure hydrocephalus and cerebral blood flow: a PET study of baseline
      values.
AB  - Regional cerebral blood flow (CBF) was studied with O(15)-water positron emission
      tomography and anatomic region-of-interest analysis on co-registered magnetic
      resonance in patients with idiopathic (n = 12) and secondary (n = 5) normal
      pressure hydrocephalus (NPH). Mean CBF was compared with values obtained from
      healthy volunteers (n = 12) and with clinical parameters. Mean CBF was
      significantly decreased in the cerebrum and cerebellum of patients with NPH. The
      regional analysis demonstrated that CBF was reduced in the basal ganglia and the
      thalamus but not in white matter regions. The results suggest that the role of
      the basal ganglia and thalamus in NPH may be more prominent than currently
      appreciated. The implications for theories regarding the pathogenesis of NPH are
      discussed.

PMID- 14688614
TI  - A new primate model of focal stroke: endothelin-1-induced middle cerebral artery
      occlusion and reperfusion in the common marmoset.
AB  - The purpose of the present set of studies was to develop a new primate model of
      focal ischemia with reperfusion for long-term functional assessment in the common
      marmoset. Initially, the cerebral vascular anatomy of the marmoset was
      interrogated by Araldite-cast and ink-perfusion methods to determine the
      feasibility of an intravascular surgical approach. The methods showed that the
      internal carotid artery was highly tortuous in its passage, precluding the
      development of an extracranial method of inducing temporary middle cerebral
      artery occlusion in the marmoset. A pilot dose-response study investigated an
      intracranial approach of topically applying endothelin-1 (ET-1) to the M2 portion
      of the middle cerebral artery in a small sample of marmosets for up to 6 hours (n
      = 2 or 3 per group). Dose-dependent reductions in middle cerebral artery vessel
      caliber followed by gradual reperfusion were inversely related to increases in
      corrected lesion volume after ET-1 treatment, relative to vehicle control
      application. Finally, the functional consequences of ET-1-induced lesions to the
      M2 vascular territory were assessed up to 24 hours after surgery using the
      optimal dose established in the pilot study (2.5 nmol/25 microL). ET-1-treated
      marmosets (n = 4) showed marked contralateral motor deficits in grip strength and
      retrieval of food rewards and contralateral sensory/motor neglect towards tactile
      stimulation, relative to their ipsilateral side and vehicle-treated marmosets (n
      = 4). Strong correlations were shown between contralateral impairments and
      histopathologic parameters, which revealed unilateral putamen and cortical damage
      to the middle cerebral artery territory. No deficits were shown on general
      mobility, and self-care was promptly resumed in ET-1 marmosets after surgery.
      These results show that this novel model of ischemia with reperfusion in the
      marmoset has the potential to assess long-term function and to gauge the efficacy
      of novel therapeutic strategies targeted for clinical stroke.

PMID- 14688615
TI  - Hypothermic protection in rat focal ischemia models: strain differences and
      relevance to "reperfusion injury".
AB  - Hypothermic protection was compared in Long-Evans and spontaneously hypertensive
      rat (SHR) strains using transient focal ischemia, and in Wistar and SHR strains
      using permanent focal ischemia. Focal ischemia was produced by distal surgical
      occlusion of the middle cerebral artery and tandem occlusion of the ipsilateral
      common carotid artery (MCA/CCAO). Moderate hypothermia of 2 hours' duration was
      produced by systemic cooling to 32 degrees C, with further cooling of the brain
      achieved by reducing to 30 degrees C the temperature of the saline drip
      superfusing the exposed occlusion site. Infarct volume was determined from serial
      hematoxylin and eosin-stained frozen sections obtained routinely at 24 hours, or
      in some cases after 3 days' survival. In the SHR, moderate hypothermia was only
      effective when initiated before recirculation after a 90-minute occlusion period.
      In contrast, the same intervention was strikingly effective in the Long-Evans rat
      even when initiated after as long as 30-minute reperfusion after a 3-hour
      occlusion. This magnitude and duration of cooling was not protective in permanent
      MCA/CCAO in the SHR, but such transient hypothermia did effectively reduce
      infarct volume after permanent occlusions in Wistar rats. These results show
      striking differences in the temporal window for hypothermic protection among rat
      focal ischemia models. As expected, "reperfusion injury" in the Long-Evans strain
      is particularly responsive to delayed cooling. The finding that the SHR can be
      protected by hypothermia initiated immediately before recirculation suggests a
      rapidly evolving component of injury occurs subsequent to reperfusion in this
      model as well. Hypothermic protection after permanent occlusion in Wistar rats
      identifies a transient, temperature-sensitive phase of infarct evolution that is
      not evident in the unreperfused SHR. These observations confirm that distinct
      mechanisms can underlie the temporal progression of injury in rat stroke models,
      and emphasize the critical importance of considering model and strain differences
      in extrapolating results of hypothermic protection studies in animals to the
      design of interventions in clinical stroke.

PMID- 14688616
TI  - Protein kinase C-gamma and calcium/calmodulin-dependent protein kinase II-alpha
      are persistently translocated to cell membranes of the rat brain during and after
      middle cerebral artery occlusion.
AB  - The levels of protein kinase C-gamma (PKC-gamma ) and the calcium/calmodulin
      dependent kinase II-alpha (CaMKII-alpha) were measured in crude synaptosomal
      (P2), particulate (P3), and cytosolic (S3) fractions of the neocortex of rats
      exposed to 1-hour and 2-hour middle cerebral artery occlusion (MCAO) and 2-hour
      MCAO followed by 2-hour reperfusion. During MCAO, PKC levels increased in P2 and
      P3 in the most severe ischemic areas concomitantly with a decrease in S3. In the
      penumbra, PKCgamma decreased in S3 without any significant increases in P2 and
      P3. Total PKC-gamma also decreased in the penumbra but not in the ischemic core,
      suggesting that the protein is degraded by an energy-dependent mechanism,
      possibly by the 26S proteasome. The CaMKII-alpha levels increased in P2 but not
      P3 during ischemia and reperfusion in all ischemic regions, particularly in the
      ischemic core. Concomitantly, the levels in S3 decreased by 20% to 40% in the
      penumbra and by approximately 80% in the ischemic core. There were no changes in
      the total levels of CaMKII-alpha during MCAO. The authors conclude that during
      and after ischemia, PKC and CaMKII-alpha are translocated to the cell membranes,
      particularly synaptic membranes, where they may modulate cellular function, such
      as neurotransmission, and also affect cell survival. Drugs preventing PKC and/or
      CaMKII-alpha translocation may prove beneficial against ischemic cell death.

PMID- 14688617
TI  - Neuroprotection after transient global cerebral ischemia in Wld(s) mutant mice.
AB  - The Wld(s) mouse mutant demonstrates a remarkable phenotype of delayed axonal and
      synaptic degeneration after nerve lesion. In this study, the authors tested the
      hypothesis that expression of Wld protein is neuroprotective in an in vivo mouse
      model of global cerebral ischemia. This model is associated with selective
      neuronal degeneration in specific brain regions such as the caudate nucleus and
      CA2 hippocampal pyramidal cell layer. The extent of neuronal damage was
      quantified in Wld(s) compared to wild-type mice after an identical episode of
      global cerebral ischemia. The results demonstrated a significant and marked
      reduction in the extent of neuronal damage in Wld(s) as compared to wild-type
      C57Bl/6 mice. In the caudate nucleus, Wld expression significantly reduced the
      percentage of ischemic neuronal damage after global ischemia (Wld(s), 27.7 +/-
      16.8%; wild-type mice, 58.7 +/- 32.3%; P = 0.036). Similarly, in the CA2
      pyramidal cell layer, there was a significant reduction of neuronal damage in the
      Wld(s) mice as compared to wild-type mice after ischemia (Wld(s), 17.7 +/- 23.0%;
      wild-type mice, 41.9 +/- 28.0%; P < 0.023). Thus, these results clearly
      demonstrate that the Wld gene confers substantial neuroprotection after cerebral
      ischemia, and suggest a new role to that previously described for Wld(s).

PMID- 14688618
TI  - Regulation of the profile of iron-management proteins in brain microvasculature.
AB  - The distribution of brain iron is heterogeneous, but the mechanism by which these
      regional differences are achieved and maintained is unknown. In this study, the
      authors test two hypotheses related to brain iron transport. The first is that
      there is regional variability in the profile of proteins associated with iron
      transport and storage in the brain microvasculature. The second hypothesis is
      that the iron status of the brain will dictate the response of the protein
      profile in the microvasculature to changes in systemic iron status. The profile
      analysis consists of transferrin (iron transport), ferritin (iron storage),
      transferrin receptor (iron uptake), and divalent metal transporter 1 (release of
      iron from endosomes). An additional protein involved in cellular iron efflux,
      ferroportin, was not detected in brain microvasculature. The results show that
      there are significantly higher levels of these proteins in the microvasculature
      from each area of the brain compared to a whole brain homogenate, but no regional
      differences within the microvasculature. The levels of ferritin observed in the
      microvasculature indicate that the microvascular endothelial cells have
      significant iron storage capacity. There are no significant changes in the
      regional protein profiles in response to systemic iron manipulation when brain
      iron status was normal. In contrast, in Belgrade rats, whose brain is iron
      deficient, the expression of both divalent metal transporter 1 and transferrin
      receptor was increased compared with control in almost all brain regions
      examined, but not transferrin or ferritin. These findings indicate that regional
      brain iron heterogeneity is not maintained by differences in microvascular iron
      management protein levels. The results also indicate that brain iron status
      dictates the response of the microvascular protein profile to systemic iron
      manipulation.

PMID- 14688620
TI  - Induced hippocampal neuron protection in an optimized gerbil ischemia model:
      insult thresholds for tolerance induction and altered gene expression defined by
      ischemic depolarization.
AB  - Preconditioning of hippocampal CA1 neurons was evaluated in a gerbil model of
      transient global ischemia using extracellular recording of DC potential shifts
      characteristic of ischemic depolarization to precisely define the duration of
      both priming and test insults. Brief ischemia resulting in depolarizations of 2.5
      to 3.5 minutes consistently induced maximal tolerance (95% protection) against
      subsequent challenges 2 days later with an approximate doubling of the insult
      duration required for complete CA1 neuron loss from 6 to 12 minutes
      depolarization when evaluated 1 week after the test insult. Significant
      protection persisted at 2 months survival, although the apparent injury threshold
      regressed to approximately 8 minutes, indicating delayed progression of injury
      after longer test insults. In situ hybridization was used to evaluate
      depolarization thresholds for induction of mRNAs encoding the 70 kDa heat
      shock/stress protein, hsp72, as well as several immediate-early genes (c-fos, c
      jun, junB, and junD). Immediate-early genes were prominently expressed after
      short insults inducing tolerance, whereas appreciable hsp72 induction only
      occurred after insults approaching the threshold for neuron injury. These results
      establish an ischemic preconditioning model with the predictability needed for
      mechanistic studies and demonstrate that prior transcriptional activation of the
      postischemic heat shock response is not required for expression of delayed
      tolerance.

PMID- 14688619
TI  - Molecular profile of vascular ion channels after experimental subarachnoid
      hemorrhage.
AB  - Cerebral vasospasm is a transient, delayed constriction of cerebral arteries that
      occurs after subarachnoid hemorrhage (SAH). Smooth muscle cells show impaired
      relaxation after SAH, which may be caused by a defect in the ionic mechanisms
      regulating smooth muscle membrane potential and Ca(2+) permeability. We tested
      this hypothesis by examining changes in expression of mRNA and protein for ion
      channels in the basilar arteries of dogs after SAH using quantitative real-time
      polymerase chain reaction (PCR) and western blotting. SAH was associated with a
      significant reduction in basilar artery diameter to 41 +/- 8% of pre-SAH diameter
      (P < 0.001) after 7 days. There was significant downregulation of the voltage
      gated K(+) channel K(v) 2.2 (65% reduction in mRNA, P < 0.001; 49% reduction in
      protein, P < 0.05) and the beta1 subunit of the large-conductance, Ca(2+) -
      activated K(+) (BK) channel (53% reduction in mRNA, P < 0.02). There was no
      change in BK beta1 subunit protein. Changes in mRNA levels of K(v) 2.2 and the BK
      beta1 subunit correlated with the degree of vasospasm (r(2) = 0.490 and 0.529
      respectively, P < 0.05). The inwardly rectifying K(+) (K(ir)) channel K(ir) 2.1
      was upregulated (234% increase in mRNA, P < 0.001; 350% increase in protein, P <
      0.001). There was no significant change in mRNA expression of L- type Ca(2+)
      channels and the BK-alpha subunit. These data suggest that K(+) channel
      dysfunction may contribute to the pathogenesis of cerebral vasospasm.

PMID- 14688621
TI  - Accumulation of calpain and caspase-3 proteolytic fragments of brain-derived
      alphaII-spectrin in cerebral spinal fluid after middle cerebral artery occlusion
      in rats.
AB  - Preclinical studies have identified numerous neuroprotective drugs that attenuate
      brain damage and improve functional outcome after cerebral ischemia. Despite this
      success in animal models, neuroprotective therapies in the clinical setting have
      been unsuccessful. Identification of biochemical markers common to preclinical
      and clinical cerebral ischemia will provide a more sensitive and objective
      measure of injury severity and outcome to facilitate clinical management and
      treatment. However, there are currently no effective biomarkers available for
      assessment of stroke. Nonerythroid alphaII-spectrin is a cytoskeletal protein
      that is cleaved by calpain and caspase-3 proteases to signature alphaII-spectrin
      breakdown products (alphaII-SBDPs) after cerebral ischemia in rodents. This
      investigation examined accumulation of calpain- and caspase-3-cleaved alphaII
      SBDPs in cerebrospinal fluid (CSF) of rodents subjected to 2 hours of transient
      focal cerebral ischemia produced by middle cerebral artery occlusion (MCAO)
      followed by reperfusion. After MCAO injury, full-length alphaII-spectrin protein
      was decreased in brain tissue and increased in CSF from 24 to 72 hours after
      injury. Whereas alphaII-SBDPs were undetectable in sham-injured control animals,
      calpain but not caspase-3 specific alphaII-SBDPs were significantly increased in
      CSF after injury. However, caspase-3 alphaII-SBDPS were observed in CSF of some
      injured animals. These results indicate that alphaII-SBDPs detected in CSF after
      injury, particularly those mediated by calpain, may be useful diagnostic
      indicators of cerebral infarction that can provide important information about
      specific neurochemical events that have occurred in the brain after acute stroke.

PMID- 14688622
TI  - Amelioration of hippocampal neuronal damage after transient forebrain ischemia in
      cyclooxygenase-2-deficient mice.
AB  - Several studies have suggested that cyclooxygenase-2 (COX-2) plays a role in
      ischemic neuronal death. Genetic disruption of COX-2 has been shown to reduce
      susceptibility to focal ischemic injury and N-methyl-d-aspartate-mediated
      neurotoxicity. The purpose of this study was to examine the effects of COX-2
      deficiency on neuronal vulnerability after transient forebrain ischemia. Marked
      upregulation of COX-2 immunostaining in neurons was observed at the early stage
      and prominent COX-2 staining persisted in the CA1 medial sector and CA2 sector
      over 3 days after ischemia. The immunohistologic pattern of COX-2 staining in
      these sectors gradually condensed to a perinuclear location. The degree of
      hippocampal neuronal injury produced by global ischemia in COX-2-deficient mice
      was less than that in wild-type mice, coincident with attenuation of DNA
      fragmentation in the hippocampus. Also, treatment with a selective COX-2
      inhibitor, nimesulide, after ischemia decreased hippocampal neuronal damages.
      These results of genetic disruption and chemical inhibition of cyclooxygenase-2
      show that inhibition of COX-2 ameliorates selective neuronal death after
      transient forebrain ischemia in mice.

PMID- 14688623
TI  - Time window of fibroblast growth factor-18-mediated neuroprotection after
      occlusion of the middle cerebral artery in rats.
AB  - To assess the time window for fibroblast growth factor-18 (FGF18)-mediated
      neuroprotection, FGF18 was administered by intravenous infusion at various times
      after transient occlusion of the middle cerebral artery (MCAO) in rats. Vehicle
      or FGF18 (100 microg x kg(-1) x h(-1)) was infused at 0.25, 0.5, 1.0, 2.0, 4.0,
      or 8.0 hours after MCAO with infarct volumes and behavioral deficits measured at
      24.0 hours after MCAO. A separate group of animals received the infusions 24
      hours after MCAO with endpoints measured at 48 hours after MCAO. Infusion of
      FGF18 reduced infarct volumes and improved scores in tests of reference and
      working memory, motor ability, and exploratory behavior. FGF18 was most
      efficacious when infused within 2 hours after MCAO. Significant reductions in
      infarct volumes and reductions in deficits of reference memory and motor activity
      were also observed with FGF18 infused 24 hours after MCAO. Measurements taken at
      infusion times before 2 hours after MCAO showed that regional cerebral blood flow
      was increased by FGF18. Administration of vehicle or FGF18 had no significant
      effect on mean arterial blood pressure, heart rate, brain temperature, blood pH,
      Pco2, or Po2. These results demonstrate that FGF18 is an effective
      neuroprotective agent when administered early after transient MCAO in rats.
      Efficacy observed with infusions at later times suggests an expanded time window
      for FGF18-mediated neuroprotection.

PMID- 14688624
TI  - Caspase inhibition after neonatal ischemia in the rat brain.
AB  - Caspase-3 has been identified as a key protease in the execution of apoptosis and
      appears to be an important downstream event after hypoxia-ischemia in the
      immature brain. The efficacy of a pan-caspase inhibitor, boc-aspartyl-(Ome)
      fluoromethyl-ketone (BAF), was tested in a model of unilateral focal ischemia
      with reperfusion in 7-day-old rats. The BAF inhibitor was given intraperitoneally
      5 minutes before reperfusion via the carotid artery. This procedure reduced the
      activity of caspase-3 by 79% but did not induce a significant reduction in
      infarct volume (23.8 +/- 7.5% versus 30.1 +/- 6.4%). Animals were distributed in
      two populations. One population exhibited an infarct, whereas the other appeared
      to be fully protected. BAF-treated animals exhibiting an infarct mostly displayed
      necrotic cell death, whereas apoptotic nuclei were observed in untreated or
      vehicle-treated animals. Repeated dose of BAF (5 minutes before and 9 hours after
      reperfusion) did not also provide benefit after neonatal ischemia, although a
      general trend to reduce lesion was observed (20.5 +/- 3.7% versus 34.4 +/- 5.9%).
      These findings raise critical questions about the use of peptide ketone apoptotic
      inhibitors in improving histopathologic outcomes after neonatal stroke.

PMID- 14688628
TI  - An update on clinical trials in pacing: is dual chamber pacing better?
AB  - PURPOSE OF REVIEW: As pacemaker technology has increased in complexity and now
      offers a variety of additional capabilities, there is uncertainty as to which
      pacing mode offers more benefit-dual-chamber or single-chamber. RECENT FINDINGS:
      Two large-scale randomized trials, the Canadian Trial of Physiologic Pacing and
      the Mode Selection Trial, demonstrated that dual-chamber pacing does not reduce
      the incidence of stroke or improve survival when compared with ventricular
      pacing. However, dual-chamber pacing does reduce the incidence of atrial
      fibrillation and in patients with sinus node dysfunction, reduces heart failure
      symptoms when compared with ventricular pacing. The modest results of these
      trials were unexpected when viewed in the context of the very favorable
      retrospective studies. SUMMARY: A rethinking of the physiology of cardiac pacing
      has led to the concept that although atrioventricular synchrony supports an
      improvement in cardiac output and ventricular pressures, these favorable
      hemodynamics may be attenuated by ventricular dyssynchrony from right ventricular
      apical pacing. In patients with a reduced ejection fraction, this dyssynchrony
      may be especially detrimental. Two trials (DANPACE and SAVE-PACE) are currently
      underway that will clarify the clinical significance of reducing forced
      ventricular desynchronization. The results of these trials may direct pacemaker
      physicians away from the right ventricular apical lead toward a new imperative of
      atrioventricular and right ventricular-left ventricular synchrony.

PMID- 14688629
TI  - Pacemaker and defibrillator lead extraction.
AB  - PURPOSE OF REVIEW: Continued growth in the elderly population and expanding
      indications have resulted in a progressive increase in the number of implants of
      pacemakers and defibrillators. Concomitant with these expanding numbers, more
      leads require removal, due especially to mechanical dysfunction, the need to
      upgrade to more complex devices, or local or systemic infection. Further, leads
      have become more complex, particularly for defibrillator systems, resulting in
      the development of powered extraction sheaths to expedite their removal. For
      these reasons, it is important to understand the expanding indications,
      procedural aspects, and limitations of arrhythmia device extraction. RECENT
      FINDINGS: Expanded indications for lead extraction include upgrade to more
      complex systems, particularly pacemaker to defibrillator or biventricular device,
      extraction through occluded vasculature to produce a conduit for reimplantation,
      more frequent removal due to vascular overload with multiple leads, and a finite
      frequency of infection, occurring particularly with device replacement or
      revision. Powered sheaths now include laser and electrocautery systems, both
      improving the ease of lead explantation. SUMMARY: Complication rates remain low
      but constant with extraction of larger numbers of leads using new technologies.
      Expansion of the use of biventricular systems, with implantation of coronary
      sinus electrodes, will continue to challenge lead extraction in terms of
      technology and safety. Design of leads that are easier to remove remains of
      paramount importance.

PMID- 14688630
TI  - An update on implantable cardioverter-defibrillator guidelines.
AB  - PURPOSE OF REVIEW: This review describes changes in indications for implantable
      cardioverter-defibrillator (ICD) implantation made in the American College of
      Cardiology, American Heart Association, and North American Society of Pacing and
      Electrophysiology 2002 update of the 1998 guideline for the implantation of
      cardiac pacemakers and antiarrhythmia devices. RECENT FINDINGS: Recent
      observational and clinical data support changes in the guidelines for ICD
      implantation to include patients with no structural heart disease and spontaneous
      ventricular tachycardia not amenable to other treatments; left ventricular
      ejection fractions of 0.30 or less at least 1 month after myocardial infarction
      and at least 3 months after coronary revascularization surgery (the Multicenter
      Automatic Defibrillator Implantation Trial II); syncope of unexplained origin or
      a family history of unexplained sudden cardiac death in association with typical
      or atypical right bundle branch block and ST-segment elevations (Brugada
      syndrome); and syncope in the setting of advanced structural heart disease when
      thorough invasive and noninvasive investigations have failed to define a cause.
      SUMMARY: With the completion of multiple important randomized clinical trials,
      the application of ICD technology continues to evolve. Indications have expanded
      from secondary to primary prevention. Most importantly, currently available data
      support the prophylactic use of ICDs in patients with coronary artery disease and
      poor left ventricular function. Further trial data are awaited to determine if
      the same benefits for survival and quality of life will be afforded to patients
      with nonischemic heart diseases and poor left ventricular function.

PMID- 14688631
TI  - Subanalyses of secondary prevention implantable cardioverter-defibrillator
      trials: antiarrhythmics versus implantable defibrillators (AVID), Canadian
      Implantable Defibrillator Study (CIDS), and Cardiac Arrest Study Hamburg (CASH).
AB  - PURPOSE OF REVIEW: Controlled trials for secondary prevention of sudden death-
      Antiarrhythmics Versus Implantable Defibrillators (AVID), Canadian Implantable
      Defibrillator Study (CIDS), and Cardiac Arrest Study Hamburg (CASH)--have been
      published and subanalyses of them provide useful clinical information on the
      outcome during the follow-up of this population. RECENT FINDINGS: Results from a
      meta-analysis showed a significant risk reduction (RR) of 25 to 27% of total
      mortality (P < 0.001) and 50 to 52% of arrhythmic death (P < 0.001). Compared
      with amiodarone, patients treated with an implantable cardioverter-defibrillator
      (ICD) in AVID had a maximal benefit in survival when the ejection fraction (EF)
      was between 20 and 34%. In CIDS, the group of higher risk (older than 70 years,
      EF less than 3.5%, and New York Heart Association class III-IV) presented a 50%
      RR of mortality. It has been demonstrated that the imbalance in beta-blocker use
      cannot explain the better survival in the ICD patients. After 3 years the
      recurrence of arrhythmia was 64% in the ICD group of the AVID trial. Patients
      enrolled after an episode of ventricular tachycardia were more likely to have
      appropriate therapy during follow-up. Older age, lower blood pressure, history of
      atrial fibrillation, diabetes, congestive heart failure, and prior pacemaker were
      parameters used for high-risk stratification. Conversely, inducibility of
      ventricular tachyarrhythmias on electrophysiology did not predict death. SUMMARY:
      Patients with ICD after ventricular tachyarrhythmias have a 28% RR in total
      mortality. Individuals with EF between 20 to 34% received the highest benefit
      with ICD therapy.

PMID- 14688627
TI  - Autonomic aspects of arrhythmogenesis: the enduring and the new.
AB  - PURPOSE OF REVIEW: Recent progress in understanding the role of the autonomic
      nervous system in the development of cardiac arrhythmias is reviewed. The focus
      is on the translation of basic principles of neural control of heart rhythm that
      have emerged from experimental studies to clinical applications. RECENT FINDINGS:
      Recent studies have made significant strides in defining the function of
      intrinsic cardiac innervation and the importance of nerve sprouting in electrical
      remodeling. A recurring theme is that heterogeneity of sympathetic innervation in
      response to injury is highly arrhythmogenic. In addition, both sympathetic and
      parasympathetic influences on ion channel activity have been found to accentuate
      electrical heterogeneities and thus to contribute to arrhythmogenesis in the long
      QT and Brugada syndromes. In the clinic, heart rate variability continues to be a
      useful tool in delineating pathophysiologic changes that result from the
      progression of heart disease and the impact of diabetic neuropathy. Heart rate
      turbulence, a noninvasive indicator of baroreceptor sensitivity, has emerged as a
      simple, practical tool to assess risk for cardiovascular mortality in patients
      with ischemic heart disease and heart failure. Evidence of the proarrhythmic
      influence of behavioral stress has been further bolstered by defibrillator
      discharge studies and ambulatory ECG-based T-wave alternans measurement. SUMMARY:
      The results of recent investigations underscore the importance of the autonomic
      influences as triggers of arrhythmia and provide important mechanistic insights
      into the ionic and cellular mechanisms involved.

PMID- 14688632
TI  - Complications of biventricular pacing.
AB  - PURPOSE OF REVIEW: Cardiac resynchronization therapy, a biventricular pacemaker
      based therapy for heart failure, is increasingly being used based on a variety of
      clinical studies. However, the complications and risks related to different
      aspects of this novel therapy are not well documented. This review summarizes the
      data derived from major clinical trials about the complications related to
      implantation, hardware, and programming of biventricular devices. RECENT
      FINDINGS: Several clinical trials have reported the complications related to
      biventricular device implantation. However, there are no reports available
      providing a comprehensive review on all the possible complications related to
      cardiac resynchronization devices. SUMMARY: With a clear understanding of the
      potential complications and meticulous approach to implant and programming, the
      incidence of complications can be minimized.

PMID- 14688633
TI  - Troubleshooting pacemakers and implantable cardioverter-defibrillators.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an update on stored
      diagnostic information furnished by new model pacemakers and implantable
      cardioverter-defibrillators (ICDs). This information provides crucial information
      about both device function and arrhythmias discovered with device interrogation
      and is invaluable when troubleshooting problems with devices. RECENT FINDINGS:
      The most recent generation of pacemakers and ICDs provides extensive diagnostic
      data regarding both device and lead function. Regular measurements of lead
      impedance and pacing thresholds allow for early detection of lead insulation
      break, fracture, dislodgement, or other problems. Analysis of stored intracardiac
      electrograms (EGMs) alerts the physician to oversensing and undersensing
      problems, which may manifest as abnormal device function, inappropriate
      arrhythmia detection, or inappropriate therapy. Simultaneous dual-chamber EGMs
      help the clinician diagnose the electrophysiologic mechanism of atrial and
      ventricular tachyarrhythmias, whether they are sustained, nonsustained,
      symptomatic, or asymptomatic. Detection and specific diagnosis of arrhythmias
      with EGMs may determine the need for anticoagulation, institution or change of
      antiarrhythmic drug therapy, or reprogramming of device detection or therapy
      parameters. Some devices also have the ability to function as patient-activated
      monitors. SUMMARY: Better diagnostic data by current pacemakers and ICDs allow
      for earlier and more accurate identification of device and lead malfunctions as
      well as better arrhythmia management. In addition, detection of asymptomatic
      clinically relevant arrhythmias may prompt actions by the physician that can
      alter clinical outcome.

PMID- 14688634
TI  - Oral class III antiarrhythmics: what is new?
AB  - PURPOSE OF REVIEW: This review describes the latest developments in the clinical
      usage of class III antiarrhythmics. It also discusses some new studies providing
      insight into the mechanism of action of these drugs. RECENT FINDINGS: New data
      suggest that amiodarone is one of the most effective drugs for management of
      ventricular as well as supraventricular tachyarrhythmias. As over the years we
      have learned to deal with the toxic side effects of this drug, the risk of
      bradyarrhythmias requiring placement of a pacemaker is becoming more significant.
      Sotalol was approved for treatment of atrial fibrillation and atrial flutter
      (AF). It was also found to be effective in management of postoperative AF.
      Dofetilide has been approved for the conversion and maintenance of sinus rhythm
      in AF; its role in ventricular arrhythmias remains unclear. Data are emerging
      regarding clinical efficacy of azimilide and dronedarone. SUMMARY: Management of
      arrhythmias in patients with structural heart disease remains a challenge. Class
      III antiarrhythmics are the mainstay of treatment in this group of patients.

PMID- 14688635
TI  - Role of intracardiac ultrasound in interventional electrophysiology.
AB  - PURPOSE OF REVIEW: Interventional procedures in the electrophysiology and
      catheterization laboratory are rapidly advancing. Critical to the advancement of
      these procedures is accurate identification of critical anatomic landmarks and
      catheter position. Fluoroscopy remains the mainstay for general identification of
      anatomic landmarks but is inadequate for the precise imaging needed for complex
      procedures. Precise imaging of anatomic landmarks and catheter position is now
      possible during the procedure with the use of intracardiac echocardiography
      (ICE). This paper reviews the rapid development and utilization of ICE in
      interventional electrophysiology. RECENT FINDINGS: Several recent studies show
      ICE as a major contribution to providing a safer, more reliable, and more cost
      effective means of accomplishing the tasks performed by existing techniques. In
      the electrophysiology laboratory, the dependence on this new technology has been
      due to the rapid development of catheter-based radiofrequency ablation of the
      pulmonary veins for treatment of atrial fibrillation. Since the initial use of
      ICE in facilitating ablation of atrial fibrillation, other uses for ICE are
      continuously being identified. SUMMARY: A comprehensive look is provided at the
      history and development of this new technology along with the most recent
      applications of ICE in interventional electrophysiology.

PMID- 14688636
TI  - Will direct thrombin inhibitors replace warfarin for preventing embolic events in
      atrial fibrillation?
AB  - PURPOSE OF REVIEW: Atrial fibrillation is the most frequently encountered
      tachyarrhythmia requiring therapy. Treatment issues include therapy for any
      reversible cause; the identification and treatment of any underlying structural
      disorder; control of the ventricular rate, both for symptom reduction and
      prevention of tachycardic-induced cardiomyopathy; restoration and maintenance of
      sinus rhythm when symptoms persist despite rhythm control; and anticoagulation in
      patients with high-risk markers for systemic embolization: age over 65 years,
      hypertension, diabetes, ventricular failure, rheumatic valvular disease, and
      prior stroke or other embolic event. In such patients, anticoagulation with
      warfarin is currently recommended. Warfarin therapy carries significant risks
      (especially bleeding), inconveniences (the cost of prothrombin time monitoring,
      the need for rigid dietary stability, the concerns of drug and herbal
      interactions), and other concerns (the issue of generic formulation
      substitution). RECENT FINDINGS: Under development are oral thrombin inhibitors.
      The first to reach clinical approval will likely be ximelagatran. In clinical
      trials to date, ximelagatran has proven to be equal to or superior to warfarin in
      the prevention and treatment of thrombophlebitis. In atrial fibrillation
      patients, the Stroke Prevention Using Oral Thrombin Inhibitor in Atrial
      Fibrillation (SPORTIF) trials completed so far appear to show a similar or better
      efficacy for ximelagatran versus warfarin as regards both prevention of embolic
      events and lower risks of major bleeding, with no serious adverse effects except
      for apparently reversible alterations in liver function tests in approximately 6%
      of subjects, all occurring early in therapy to date. If the remaining SPORTIF
      trial (SPORTIF V) is confirmatory (results to be available in late 2003), it is
      expected that this exciting new product will be submitted this winter to the Food
      and Drug Administration for approval. Recent findings also include the
      observations in the Atrial Fibrillation Follow-up Investigation of Rhythm
      Management (AFFIRM) and Rate Control Versus Electrical Cardioversion (RACE)
      trials that anticoagulation should not be discontinued despite the restoration
      and maintenance of sinus rhythm. SUMMARY: Oral direct thrombin inhibitors, such
      as ximelagatran, appear likely to replace the use of warfarin in most patients in
      the near future, because of a better risk-benefit profile.

PMID- 14688638
TI  - Learning takes a lifetime.

PMID- 14688637
TI  - Ablation of tachyarrhythmias in pediatric patients.
AB  - PURPOSE OF REVIEW: Radiofrequency (RF) ablation treatment for tachyarrhythmias
      has been available only for the past 15 years. The success rates have been
      excellent with a very low frequency of complications. Because of this efficacy,
      the use of RF ablation in children has become standard of care even though long
      term data are unavailable. In this review, common tachyarrhythmias and their
      current treatments in children will be discussed. RECENT FINDINGS: Novel
      electrophysiology technologies such as electroanatomic mapping and sophisticated
      ablating catheters have improved success rates and decreased complications. The
      improvement is also due to better understanding of the mechanisms and etiologies
      of tachyarrhythmias. Both have positively impacted success rates and have made
      more complicated tachyarrhythmias treatable with ablation. SUMMARY: The
      technologic advances in ablation and improved understanding of tachyarrhythmias
      over the past 15 years have greatly improved outcomes in ablative treatment of
      tachyarrhythmias in children. In most cases this method of treatment is the
      preferred first-line approach to symptomatic tachyarrhythmias in children.

PMID- 14688639
TI  - Care tips for chronic wounds: lower-extremity ulcers.

PMID- 14688640
TI  - Wound care for patients with diabetes.

PMID- 14688642
TI  - Healing wounds from the inside out.

PMID- 14688643
TI  - Diverse learning opportunities mark the clinical symposium.

PMID- 14688644
TI  - Use of electrotherapy to reverse expanding cutaneous gangrene in end-stage renal
      disease.

PMID- 14688645
TI  - Nutritional nonadherence and wound healing.

PMID- 14688646
TI  - 5 Questions--and answers--about MIRE treatment.

PMID- 14688647
TI  - Skin and wound biopsy: when, why, and how.

PMID- 14688648
TI  - Academic nature of nurse education gets criticized.

PMID- 14688649
TI  - Language relating to mental health must be used with care.

PMID- 14688650
TI  - Nurse manager's persistent neglect of residents in a nursing home.

PMID- 14688651
TI  - 12-lead ECG interpretation 2: right ventricular and posterior infarcts.
AB  - Some myocardial abnormalities can have serious consequences if not detected, and
      may negatively affect overall patient outcomes. Right ventricular and posterior
      myocardial infarction are two types of myocardial injury that may seriously
      affect the patient's haemodynamics status, but can be recognized easily if
      appropriate specialized 12-lead electrocardiograms (ECGs) are recorded and
      analysed. The nurse is best-placed to conduct advanced ECG interpretation, in
      partnership with medical colleagues, and taking into account the patient's
      clinical symptoms and cardiac risk factors. This article should be read in
      conjunction with the first article (Vol 12(21): 1248-55).

PMID- 14688652
TI  - Perceptions of nurses with regard to doctor-patient communication.
AB  - The objective of this study was to evaluate nurses' perceptions of communication
      between doctors and patients with cancer, AIDS and rheumatoid arthritis. A cross
      sectional study was conducted with 741 nurses in 12 hospitals. Nurses received a
      self-questionnaire that included questions on personal value and attitudes. The
      answers were used in constructing affective variables (religious beliefs,
      attitude towards death, paternalism). The prevalence of explicit communication in
      'nurse perception of doctor-patient communication' in the case of cancer was
      4.5%, with AIDS 30%, and with rheumatoid arthritis 41.8%. When the value of
      communication was evaluated, it became evident that the likelihood of a nurse
      perceiving explicit communication in reference to a diagnosis of cancer was 6.5
      time greater when communication was considered to be of greater value (CI 95% 2.6
      6.6). For nurses who accept the possibility of death, the likelihood of
      perceiving explicit communication in the case of AIDs was 7.4 times greater than
      for nurses who deny this possibility (CI 95% 3.7-14.7), and when nurses displayed
      a deeply religious attitude, the likelihood of perceiving explicit communication
      was 80% greater than for nurses without this attitude (CI 95% 1.1-2.9). Nurses
      participate actively in the process of attending to patients with cancer and
      other disabling illnesses. Thus, there is a need for health professionals who
      provide compassionate attention, which will improve the various
      interrelationships between nurses and patients.

PMID- 14688653
TI  - Issues involved in promoting patient autonomy in health care.
AB  - Respecting patient autonomy is a central part of the Royal College of Nursing's
      definition of nursing (RCN, 2003). Although autonomy is a fundamental ethical
      principle in health care, it stands alongside the principles of beneficence, non
      maleficence and justice (Wilmot, 2003), and these principles may be interpreted
      differently by individuals and professional groups. In seeking to promote patient
      autonomy, it is therefore necessary for nurses to consider how these principles
      interlink, and to understand the potentially differing interpretations that they
      may encounter in practice. This article sets out to address these issues and
      suggests that facilitating patient autonomy includes engaging in debates which
      include uncertainties, considering the resource implications of patient autonomy
      and the responsibilities that patients have themselves. It also identifies that
      nurses who aim to promote patient autonomy and holistic decision making need to
      be able to facilitate discussion that may include questioning the dominant
      biomedical view of health. This will be problematic if nurses do not themselves
      feel empowered or autonomous.

PMID- 14688654
TI  - Consent and the mentally disordered detained patient.

PMID- 14688655
TI  - Interprofessional practice and learning disability nursing.
AB  - Several decades of policy and service change in the field of learning disability
      have set in place new service boundaries in health and social care, leading to
      different working relationships for professionals based on interprofessional and
      interagency collaboration. However, economic pressures may result in agencies
      offering resource-led rather than needs-led services, resulting in fragmented
      services and tensions between professional groups faced with tough choices in
      order to meet the long-term needs of people with learning disabilities. One of
      the key roles of the registered learning disability nurse (RLDN) is that of
      facilitator in meeting the healthcare needs of people with learning disabilities,
      which involves interprofessional working across these new health and social care
      boundaries. The aim of this article is to present the findings from a small scale
      research study that was undertaken to explore the views of the RLDN group in
      relation to interprofessional practice in the long-term support of people with
      learning disabilities. Set within a grounded theory methodology, this article
      focuses on one element of the research study, which was a descriptive analysis of
      individual practitioners' experiences. In documenting the practitioners'
      accounts, the research begins to identify a series of key roles and significant
      practice knowledge held by those employed in learning disability nursing
      positions.

PMID- 14688658
TI  - Communication must improve for success.

PMID- 14688656
TI  - Pain related to Optiva 2, Biovalve, and Venflon 2 intravenous catheters.
AB  - Pain related to the insertion of intravenous catheters is a major issue for many
      patients. This study investigated differences in pain on insertion for three
      different catheters - Optiva 1, Biovalve and Venflon 2 - as assessed by 100
      volunteers. Clinicians also assessed a variety of parameters related to their
      overall ease of use. This study demonstrates that Optiva 2 can offer significant
      benefits for both patient and clinician. Pain on insertion was significantly
      lower with Optiva 2 than with Venflon 2, but comparable with Biovalve. Ease of
      insertion and flashback were significantly better for Optiva 2 than for Venflon
      2, but similar to Biovalve. For the parameters 'ease of catheter advancement' and
      'overall ease of use', the operators rated Optiva 2 significantly better than
      Biovalve and Venflon 2.

PMID- 14688657
TI  - Value of clinical teaching must be recognized.

PMID- 14688659
TI  - Hospital secondments of community nurses to improve stoma care.
AB  - As clinical nurse specialists working in a busy and proactive colorectal team we
      are continually looking for different ways of working to enhance patient care.
      The opportunity to review the range of skills in the team highlighted the need
      for a staff nurse. It was decided that this role should be an educational
      secondment (on a rolling programme) to give staff nurses the opportunity to
      develop skills in colorectal nursing. The post was piloted with a community staff
      nurse for it was felt that this would improve the primary/secondary interface,
      communication and collaborative working between the teams. The aim was to empower
      generalist and community nurses in the care of patients with colorectal diseases.
      This was delivered through a work-based programme to help develop the knowledge
      and skills of the nurses, in addition to enhancing multidisciplinary teamworking,
      in an environment of mutual regard and shared understanding.

PMID- 14688660
TI  - Multidisciplinary communication in the Irish public health nursing service: a
      study.
AB  - Public health nurses (PHNs) in the Republic of Ireland work as part of a
      multidisciplinary team in the delivery of community care services. Good
      interdisciplinary communication is therefore vital to enable them to offer the
      best possible care to their clients. This article reports on one section of a
      national survey of PHNs who work with families with infants. The findings suggest
      that although in general, PHNs reported good working relationships with other
      professionals - particularly with speech therapists, area medical officers and
      community welfare officers - the same could not be said for hearing and eye
      specialists. Feedback also varied according to professional groups, with less
      than one third of PHNs reporting they always received feedback from GPs, eye
      specialists or social workers. A significant statistical correlation was found
      between reported working relationships and the frequency that feedback was
      received. These findings have implications for communication and teamworking in
      primary care in the Republic of Ireland and elsewhere.

PMID- 14688662
TI  - Court appearance 1: the English and Welsh court system.

PMID- 14688661
TI  - Management of functional constipation in childhood.
AB  - Functional constipation is a common condition. In the majority of cases the
      constipation develops as a result of a complex weave of factors including
      specific triggers, e.g. reduced fluid intake following a viral infection or
      periods of restricted access to the toilet. The passage of large painful stools
      perpetuates the problem when the child begins to associate pain with defecation.
      The management of constipation can often be a challenge in children, who
      initially may be reluctant to sit on the toilet. This article will discuss the
      contributory factors to the cause of constipation and identify the keys to
      successful treatment, including ensuring a holistic child-focused approach with
      effective initial evacuation and appropriate maintenance therapy.

PMID- 14688663
TI  - The role of cranberry juice in the treatment of urinary tract infections.
AB  - There has long been an interest in the use of cranberry, usually as a juice, to
      prevent and treat urinary tract infections (UTI). This mini-review examined the
      evidence available using a simple search on an internet-based resource designed
      to make evidence readily available to practitioners in the South Eastern NHS
      regions of the UK. The resource, known as KA24, provides access to a range of
      databases and full text of journal articles. The first stage of the review
      identified two existing Cochrane Reviews, one examining cranberry as a treatment,
      the other as prevention. Both concluded that there was insufficient evidence to
      recommend the use of cranberry in treating UTIs, although some weak research did
      offer support for cranberry juice in preventing UTIs. A search for further
      evidence not included in the Cochrane review identified several new reviews and
      two randomized controlled trials (RCTs) of cranberry as prevention. The reviews
      were not systematic and came to contradictory conclusions. They were based on a
      selective reading of the evidence base and gave no criteria for determining the
      inclusion or validity of studies. One of the RCTs was available for full scrutiny
      and was appraised as a valid study. Both RCTs found that cranberry (as juice or
      capsule) significantly reduced the rate of UTI in sexually active women. There is
      evidence to support the use of cranberry to prevent UTI in some populations but
      none to support its use as a treatment.

PMID- 14688664
TI  - So you want to do research? 5: Questionnaire design.
AB  - This article describes the key aspects in the design, construction and adaptation
      of survey questionnaires. There are different types of questionnaire, each of
      which has its advantages and disadvantages. Aspects of constructing the
      questionnaire are discussed in detail; choosing the mode of administration; the
      objectives of the survey; availability of resources; characteristics of the
      target population; and quality of data. Issues concerning the identification of
      the questionnaire's content, wording and sequencing of the questions through to
      the overall appearance and layout of the questionnaire are also considered.
      Differences in the role of open-ended and closed questions, together with their
      strengths and weaknesses, are outlined, and the need to undertake pre-testing and
      piloting as an integral part of questionnaire development is highlighted.
      Finally, issues around the adaptation of existing questionnaires are discussed
      with particular emphasis on their use in different language and cultural groups,
      and the need to achieve conceptual, content, semantic, operational and functional
      equivalence is described. An overview of the translation process is provided.

PMID- 14688665
TI  - Nurses are more than the sum of their parts.

PMID- 14688670
TI  - Peer review.

PMID- 14688671
TI  - The peer-review process in medical publishing: a reviewer's perspective.

PMID- 14688672
TI  - Atrial fibrillation I: a new classification system.

PMID- 14688673
TI  - Atrial fibrillation II: rationale for surgical treatment.

PMID- 14688674
TI  - Positron emission tomography with 2-[18f]fluoro-2-deoxy-D-glucose: can it be used
      to accurately stage the mediastinum in non-small cell lung cancer as an
      alternative to mediastinoscopy?

PMID- 14688675
TI  - Improving outcomes for women after coronary artery bypass grafting: a case for
      prevention.

PMID- 14688676
TI  - Long-term benefits of coronary bypass surgery: are the gains for women less than
      for men?

PMID- 14688677
TI  - Regional low-flow perfusion provides comparable blood flow and oxygenation to
      both cerebral hemispheres during neonatal aortic arch reconstruction.
AB  - OBJECTIVE: The aim of this study was to measure cerebral oxygenation, cerebral
      blood volume index, and cerebral blood flow velocity values in both cerebral
      hemispheres before, during, and after regional low-flow cerebral perfusion for
      neonatal aortic arch reconstruction and to test the hypothesis that cerebral
      blood volume index measured by near infrared spectroscopy correlates with
      cerebral blood flow velocity measured by transcranial Doppler ultrasonography.
      METHODS: Bilateral near infrared spectroscopy and transcranial Doppler
      ultrasonography sensors were placed, and values were recorded immediately before,
      during, and after regional low-flow cerebral perfusion at 18 degrees C. Cerebral
      oxygen saturations, cerebral blood flow velocities, and cerebral blood volume
      index values were compared by Mann-Whitney U test. Correlations between values of
      cerebral blood volume index and cerebral blood flow velocity were tested with
      Spearman rank order correlation. RESULTS: Twenty patients were studied. Median
      cerebral oxygen saturations for the right and left sides were 95% and 95% before
      regional low-flow cerebral perfusion, 95% and 87% during regional low-flow
      cerebral perfusion (P =.054), and 93% and 94% after regional low-flow cerebral
      perfusion. Median cerebral blood flow velocity values did not change during
      regional low-flow cerebral perfusion. Cerebral blood volume index exhibited a
      poor correlation with cerebral blood flow velocity. CONCLUSIONS: Regional low
      flow cerebral perfusion provides comparable blood flows and oxygenation to both
      cerebral hemispheres. Transcranial Doppler ultrasonography is recommended as a
      corroborative method with near-infrared spectroscopy to guide flow during
      regional low-flow cerebral perfusion, because cerebral blood volume index does
      not correlate with cerebral blood flow velocity.

PMID- 14688678
TI  - Perventricular device closure of muscular ventricular septal defects on the
      beating heart: technique and results.
AB  - OBJECTIVE: Both surgical management and percutaneous device closure of muscular
      ventricular septal defects have drawbacks and limitations. This report describes
      our initial experience with intraoperative device closure of muscular ventricular
      septal defects without cardiopulmonary bypass in 6 consecutive patients. METHODS:
      A median sternotomy or a subxiphoid minimally invasive incision was performed.
      Under continuous transesophageal echocardiographic guidance, the right ventricle
      free wall was punctured, and a wire was introduced across the largest defect. The
      Amplatzer (AGA Medical Corporation, Golden Valley, Minn) muscular ventricular
      septal defect occluding device (a self-expandable double-disk device) was used.
      An introducer sheath was fed over the wire, with the sheath tip positioned in the
      left ventricle cavity. The device was then advanced inside the sheath and
      deployed by retracting the sheath. Associated cardiac lesions, if any, can then
      be repaired during cardiopulmonary bypass. A similar technique can also be
      applied for periatrial closure of complex atrial septal defects. RESULTS: The
      initial 6 patients are presented. Cardiopulmonary bypass was not needed in any
      patient for placement of the device and needed in 4 patients for repair of
      concomitant malformations only (double-outlet right ventricle, aortic arch
      hypoplasia, pulmonary artery band removal). No complications from using this
      technique occurred. Discharge echocardiograms showed no significant shunting
      across the ventricular septum. CONCLUSIONS: Perventricular closure of multiple
      muscular ventricular septal defects is safe and effective. We believe that this
      could become the treatment of choice for any infant with muscular ventricular
      septal defects or any child with muscular ventricular septal defect and
      associated cardiac defects.

PMID- 14688679
TI  - Pulmonary blood pressure, not flow, is associated with net endothelin-1
      production in the lungs of patients with congenital heart disease and normal
      pulmonary vascular resistance.
AB  - OBJECTIVE: Endothelin-1 concentrations are increased in patients with increased
      mean pulmonary arterial pressure, pulmonary blood flow, and pulmonary vascular
      resistance. However, endothelin-1 concentrations have not been well characterized
      in patients with congenital heart disease and normal pulmonary vascular
      resistance. In particular, it is unclear whether pressure or flow is the key
      regulator of endothelin- 1 in this setting. We tested the hypothesis that
      pulmonary blood pressure and not flow is associated with net endothelin-1
      production in patients with congenital heart disease and normal pulmonary
      vascular resistance. METHODS: With a commercially available immunoassay, we
      measured endothelin-1 concentrations in pulmonary arterial and pulmonary venous
      plasma of 56 consecutive patients with congenital heart disease and pulmonary
      vascular resistance less than 2 U. m(2) undergoing cardiac catheterization. We
      used multiple linear regression to analyze the effect of demographic and
      hemodynamic variables on pulmonary arterial and venous endothelin-1
      concentrations and on the change of endothelin-1 concentration over the pulmonary
      vascular bed. RESULTS: Multiple linear regression revealed that of all the
      hemodynamic variables tested, mean pulmonary arterial pressure had the greatest
      effect on increasing the change of endothelin-1 concentration over the pulmonary
      vascular bed (P <.0001). Pulmonary blood flow did not have any effect on
      endothelin-1 concentrations or on the change of endothelin-1 concentration over
      the pulmonary vascular bed. CONCLUSIONS: This study shows that pulmonary blood
      pressure and not flow is associated with net endothelin-1 production in patients
      with congenital heart disease and normal pulmonary vascular resistance.

PMID- 14688680
TI  - Does hyperoxia affect glucose regulation and transport in the newborn?
AB  - OBJECTIVE: Hyperglycemia has been found to occur in children placed on
      cardiopulmonary bypass. Our laboratory demonstrated that hyperoxia plays a role
      in this hyperglycemic response and also occurs in the absence of cardiopulmonary
      bypass. The purpose of this study was to elucidate potential mechanisms
      underlying the hyperoxic-induced hyperglycemia by examining glucagon, insulin,
      and epinephrine, which are important in glucose regulation and skeletal and
      cardiac glucose transporters (GLUT1 and GLUT4), which facilitate glucose entry.
      METHODS: Three-day-old piglets were anesthetized, intubated, and ventilated to
      normoxia. Animals were then randomly allocated to either 5 hours of normoxia (n =
      4) or hyperoxia (n = 6). Measurements of oxygen, blood glucose, plasma glucagon,
      insulin, and epinephrine levels were made. Total GLUT1 and GLUT4 content in
      cardiac and skeletal muscle was measured using Western blotting analysis.
      RESULTS: A sustained hyperglycemic response (P <.001) was seen throughout the 5
      hour ventilatory period. A significant twofold elevation in glucagon levels (P
      <.001) and a threefold elevation (P <.003) in plasma insulin levels occurred,
      despite no significant changes in plasma epinephrine. Total GLUT1 and GLUT4
      content were significantly reduced in skeletal muscle by 66% and 59%,
      respectively, while no significant changes occurred in cardiac muscle.
      CONCLUSION: This study demonstrates that significant elevations in glucagon and
      insulin and reductions in total skeletal muscle GLUT1 and GLUT4 content all
      contribute to hyperoxia-induced hyperglycemia seen in newborns. To optimize
      postoperative recovery of newborns, consideration should be given to the levels
      of oxygen used to avoid the potential development of insulin resistance and
      subsequent decrease in glucose entry.

PMID- 14688681
TI  - Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac
      surgery.
AB  - BACKGROUND: There has been increasing recognition of adverse neurodevelopmental
      sequelae in some children after repair of congenital heart defects. Even among
      children with the same cardiac defect, significant interindividual variation
      exists in developmental outcome. Polymorphisms of apolipoprotein E have been
      identified as a risk factor for worse neurologic recovery after central nervous
      system injury. METHODS: A single-institution prospective study of patients <or=6
      months of age undergoing cardiopulmonary bypass for repair of congenital heart
      defects was undertaken to evaluate the association between apolipoprotein E
      genotype and postoperative neurodevelopmental dysfunction. Developmental outcomes
      were evaluated at 1 year of age by using the Bayley Scales of Infant Development.
      RESULTS: One-year evaluation was performed in 244 patients. After adjustment for
      preoperative and postoperative covariates-including gestational age, age at
      operation, sex, race, socioeconomic status, cardiac defect, and use of deep
      hypothermic circulatory arrest-the apolipoprotein E epsilon2 allele was
      associated with a worse neurologic outcome as assessed by the Psychomotor
      Developmental Index of the Bayley Scales of Infant Development (P =.036).
      Patients with the apolipoprotein E epsilon2 allele had approximately a 7-point
      decrease in the Psychomotor Developmental Index. CONCLUSIONS: Apolipoprotein E
      epsilon2 allele carriers had significantly lower Psychomotor Development Index
      scores at 1 year of age after infant cardiac surgery. The effect was independent
      of ethnicity, socioeconomic status, cardiac defect, and use of deep hypothermic
      circulatory arrest. An effect of the apolipoprotein E epsilon4 allele was not
      detected. Genetic polymorphisms that decrease neuroresiliency and impair neuronal
      repair after central nervous system injury are important risk factors for
      neurodevelopmental dysfunction after infant cardiac surgery.

PMID- 14688682
TI  - Staged repair of pulmonary atresia with ventricular septal defect and major
      aortopulmonary collateral arteries: experience with 104 patients.
AB  - OBJECTIVE: To determine the early and intermediate-term outcome of the staged
      repair used to treat children with pulmonary atresia with ventricular septal
      defect and major aortopulmonary collateral arteries. METHODS: We reviewed a
      retrospective case series of 104 patients with this complex lesion. Information
      was obtained from medical records and referring physicians. RESULTS: Of the 104
      patients treated with the staged repair, 58 achieved completion of anatomic
      repair. The 10-year mortality was 16.5%. In the patients with complete repair,
      the median right-to-left ventricle pressure ratio was 0.5. The overall surgical
      reoperation rate was 17%, and 15.5% of patients required postoperative
      interventional cardiac catheterization. In the multivariate analysis, the number
      of collateral vessels incorporated in the repair was found to be an independent
      risk factor for postoperative mortality and an elevated right-to-left ventricle
      pressure ratio after complete repair. CONCLUSION: The staged repair can be
      successfully used to treat patients with pulmonary atresia with ventricular
      septal defect and major aortopulmonary collateral arteries. This method yields a
      relatively low mortality with good functional results.

PMID- 14688683
TI  - Prevalence and predictors of neoaortic regurgitation after arterial switch
      operation for transposition of the great arteries.
AB  - BACKGROUND: The fate of the native pulmonary valve after arterial switch
      operation is still unknown and may become a cause for a secondary aortic valve
      operation during adult life. We evaluated the prevalence and predictive factors
      associated with neoaortic valvular regurgitation by a retrospective study of
      children who underwent arterial switch operation for transposition of the great
      arteries. METHODS: The onset of neoaortic valvular regurgitation was correlated
      with demographic data, cardiac anatomy, surgical technique, and postoperative
      ventricular function. The size of the neoaortic root and ascending aorta was
      measured in a selected subset of patients. RESULTS: Among 253 survivors, 173 were
      eligible for the study. After a median follow-up time of 8.2 years, 61 patients
      showed echocardiographic or angiographic evidence of valvular incompetence, which
      was progressive in 14 cases; this led to surgical intervention in 2 patients, and
      there was 1 operative death. At multivariate analysis, the onset of valvular
      regurgitation was correlated with the trap-door technique for coronary
      reimplantation (P <.01). A smooth transition from the aortic sinus to the
      ascending aorta, with loss of the normal sinotubular junction geometry, may be
      associated with valvular incompetence. CONCLUSIONS: After arterial switch
      operation, there is an increasing frequency of neoaortic regurgitation, which may
      lead to significant valvular dysfunction later in life. The trap-door type of
      coronary reimplantation is associated with an increased risk for valvular
      dysfunction, possibly because of a distortion of the sinotubular junction
      geometry. For this reason, we recommend the punch technique for repair in all but
      the most complicated coronary pattern.

PMID- 14688684
TI  - Impaired systemic ventricular relaxation affects postoperative short-term outcome
      in Fontan patients.
AB  - OBJECTIVES: Systemic ventricular end-diastolic pressure has been used as a
      predictor of outcome in patients undergoing the Fontan operation. However, this
      index only evaluates late diastolic function and does not assess active
      ventricular relaxation during the phase of early diastole, a key component of
      systemic venous pathway flow. This study sought to examine whether impaired
      preoperative systemic ventricular relaxation, expressed as the time constant of
      isovolumic relaxation (tau), affects short-term postoperative outcome in Fontan
      patients. METHODS: All patients who underwent Fontan operation between May 1998
      and November 2001 were enrolled. Tau was calculated from digitized preoperative
      systemic ventricular pressure tracings. Standard preoperative invasive indices
      were also recorded and analyzed. These independent variables were then entered
      into a multiple stepwise regression model, with length of intensive care unit
      stay, length of hospital stay, and prolonged pleural effusion as outcome
      variables. RESULTS: Twenty-seven patients fulfilled inclusion criteria. Systemic
      left ventricle predominated, and all patients had undergone prior staged
      palliation. Extracardiac Fontan was the commonest operative technique. Of the
      independent variables examined, tau was the only statistically significant
      predictor of length of intensive care unit stay (P <.001) and length of hospital
      stay (P =.002). None of the independent variables predicted pleural effusion
      greater than 10 days. CONCLUSIONS: Tau was the only significant preoperative
      invasive predictor of short-term outcome in the Fontan patients. This illustrates
      the importance of systemic ventricular relaxation and highlights the need for a
      more comprehensive assessment of diastolic function before the Fontan operation.

PMID- 14688685
TI  - The influence of hemodilution on outcome after hypothermic cardiopulmonary
      bypass: results of a randomized trial in infants.
AB  - BACKGROUND: We hypothesized that cognitive impairment and hemodynamic instability
      after infant cardiac surgery with cardiopulmonary bypass might be exacerbated by
      hemodilution. METHODS: In a single-center randomized trial with blinded
      assessment of outcomes, we compared use of 2 hemodilution protocols during
      hypothermic cardiopulmonary bypass with infant cardiac surgery. The primary
      perioperative end point was lowest cardiac index in the first 24 hours
      postoperatively, and primary end points at age 1 year were scores on the
      Psychomotor Development Index and Mental Developmental Index of the Bayley
      Scales. RESULTS: Among 147 subjects, 74 were assigned to the lower-hematocrit
      strategy (21.5% +/- 2.9%, mean +/- SD at onset of low-flow bypass) and 73 to the
      higher-hematocrit strategy (27.8% +/- 3.2%). In intent-to-treat analyses the
      lower-hematocrit group had lower nadirs of cardiac index (P =.02), higher serum
      lactate levels 60 minutes after cardiopulmonary bypass (P =.03), and a greater
      percentage increase in total body water on the first postoperative day (P =.006).
      Blood product use and adverse events were similar in the 2 groups. At age 1 year
      (113 children), the lower-hematocrit group had worse scores on the Psychomotor
      Development Index (81.9 +/- 15.7 vs 89.7 +/- 14.7, P =.008), as well as more
      Psychomotor Development Index scores at least 2 SDs below the population mean
      (16/56 [29%] vs 5/53 [9%], P =.01). The groups had similar Mental Developmental
      Index scores and findings on neurologic examination. Inferences using hematocrit
      as a continuous variable were similar to those based on intent-to-treat analyses.
      CONCLUSIONS: Hemodilution to a hematocrit level in wide use for cardiopulmonary
      bypass and thought to be safe is associated with adverse perioperative and
      developmental outcomes in infants.

PMID- 14688686
TI  - Remote control of pulmonary blood flow: initial clinical experience.
AB  - OBJECTIVE: After positive experimental results were obtained with the FloWatch-R
      PAB (EndoArt S.A., Lausanne, Switzerland), an implantable device for pulmonary
      artery banding with telemetric control, it was tested in a prospective,
      multicenter clinical trial. METHODS: From June to September 2002, 6 patients with
      a mean age of 10.6 months (1-31 months) and a mean weight of 6.5 kg (3.5-11 kg)
      underwent pulmonary artery banding with the implantation of the FloWatch-R-PAB
      device through median sternotomy (4 patients) or left thoracotomy (2 patients).
      The diagnoses were the following: univentricular heart (2 patients), complete
      atrioventricular septal defect (2 patients), ventricular septal defect (1
      patient), and multiple ventricular septal defects with double aortic arch (1
      patient). The associated procedures were atrioseptostomy with cardiopulmonary
      bypass (2 patients), closure of patent ductus arteriosus (2 patients), and
      division of double aortic arch (1 patient). RESULTS: In a mean follow-up of 7
      months (6-9 months), there were no early or late deaths, reoperations, or device
      related complications. A mean of 5 regulations per patient (range 2-14) were
      required to adjust the tightening of the pulmonary artery banding, 50% (15/30)
      within the first postoperative week, 20% (6/30) during the second week, and 30%
      (9/30) within 8 months after surgery. In 70% (21/30) of the cases, the regulation
      was required to further narrow the pulmonary artery, and in 30% (9/30) of the
      cases, the regulation was required to release the pulmonary artery. CONCLUSIONS:
      The initial trial confirmed the adequate functioning of the FloWatch-R-PAB device
      as telemetrically adjustable pulmonary artery banding. Repeated pulmonary artery
      banding adjustments, dictated by the clinical need in all patients even weeks
      after surgery, were accomplished without need for reoperation or invasive
      procedures. In children requiring pulmonary artery banding, the therapeutic
      strategies can be expanded by this promising technology. This device should be
      particularly indicated in patients with transposition of the great arteries
      requiring left ventricular retraining.

PMID- 14688687
TI  - Improved early outcome for end-stage dilated cardiomyopathy in children.
AB  - OBJECTIVE: To review the impact of management changes on the early outcomes of
      end-stage dilated cardiomyopathy in children. METHODS: We conducted a
      retrospective study of all consecutive children with end-stage dilated
      cardiomyopathy who received hospital treatment since 1992. Over the past 3 years
      the following management changes were made: (1) more aggressive use of mechanical
      cardiac assistance; (2) high priority listing for transplantation; and (3) ABO
      incompatible transplants for infants. Outcomes for 46 patients admitted between
      1992 and 1999 (group I) were compared with 53 patients between 2000 and March
      2003 (group II). RESULTS: In group I, 12 (26%) patients received mechanical
      support with recovery in 3 and transplantation in 5 (1 died). In group II, 19
      (36%) patients received extracorporeal membrane oxygenation, with recovery in 5
      and transplantation in 12 (all survived). The use of mechanical assistance was
      associated with high morbidity related to bleeding, end-organ failure, and long
      term mechanical ventilation. Five patients in group II received ABO incompatible
      transplants and all survived. There have been no episodes of rejection or need
      for increased immunosuppressive therapy. Hospital mortality has been
      significantly reduced (group I, 37% vs group II, 11%; P <.05). CONCLUSIONS:
      Recent refinements in the management of end-stage dilated cardiomyopathy in
      children have significantly reduced early mortality. Identification of markers of
      early myocardial recovery and development of mechanical devices for longer term
      and more physiologic support are essential to achieve further improvements in
      outcome.

PMID- 14688688
TI  - Surgery for atrial fibrillation using radiofrequency catheter ablation.
AB  - OBJECTIVE: We present the results obtained in 40 patients with chronic atrial
      fibrillation using direct intraoperative radiofrequency to perform atrial
      fibrillation surgery. METHODS: Between April 2001 and June 2002, 40 patients
      underwent surgery for atrial fibrillation using radiofrequency ablation and
      cardiac surgery at the Department of Cardiovascular Surgery of the University of
      Bologna [corrected]. There were 8 men and 32 women with a mean age of 62 +/- 11.6
      years (range: 20 to 80 years). RESULTS: Concomitant surgical procedures were:
      mitral valve replacement (n = 13), mitral valve replacement plus tricuspid
      valvuloplasty (n = 11), combined mitral and aortic valve replacement (n = 8), and
      combined mitral and aortic valve replacement plus tricuspid valvuloplasty (n =
      5). Moreover, 1 patient underwent tricuspid valvuloplasty plus atrial septal
      defect repair, another required aortic valve replacement plus coronary artery
      bypass graft, and a third underwent aortic valve replacement. After the mean
      follow-up time of 16.5 +/- 2.5 months survival was 92.8% and the overall
      cumulative rate of sinus rhythm was 88.5%. CONCLUSIONS: We conclude that the
      radiofrequency ablation procedure is a safe and effective means of curing atrial
      fibrillation with negligible technical and time requirements, allowing recovery
      of the sinus rhythm and atrial function in the great majority of patients with
      atrial fibrillation who underwent cardiac surgery (88.5% of our study
      population).

PMID- 14688689
TI  - Surgery modifies cardiac sensory transduction.
AB  - OBJECTIVE: We sought to determine whether cardiac surgery, specifically the
      placement of an incision within a ventricular wall, affects the capacity of
      regional cardiac sensory nerve terminals (neurites) to transduce the local
      cardiac milieu. METHODS: The capacity of sensory neurites in the right
      ventricular outflow tract associated with afferent neurons in nodose ganglia to
      transduce their mechanical and chemical milieu was studied in 11 anesthetized
      pigs before and after performing a local ventriculotomy. RESULTS: Right
      ventricular outflow tract sensory neurites associated with 23 nodose ganglion
      afferent neurons were identified that transduced local mechanical deformation
      along with substance P. The capacity of these sensory neurites to transduce these
      stimuli was almost totally obtunded after local ventriculotomy. CONCLUSIONS: The
      capacity of afferent neurons to transduce the cardiac milieu can be modified by
      cardiac surgical interventions. This may have negative implications with respect
      to how the entire cardiac neuronal hierarchy transduces alterations in the
      cardiac milieu postsurgery. This fact should be taken into account when
      contemplating the placement of cardiac incisions during surgery.

PMID- 14688690
TI  - Comparative efficacies and durations of action of phenoxybenzamine,
      verapamil/nitroglycerin solution, and papaverine as topical antispasmodics for
      radial artery coronary bypass grafting.
AB  - OBJECTIVE: Radial arteries are increasingly used as conduits for coronary artery
      bypass grafts, but perioperative graft vasospasm continues to be a concern.
      Phenoxybenzamine, verapamil/nitroglycerin solution, and papaverine have been
      advocated as topical antispasmodic agents. We compared the relative efficacies
      and durations of action of these agents. METHODS: Isometric tension developed in
      response to clinically important vasoconstrictors was measured in 100 radial
      artery rings (from patients undergoing coronary artery bypass grafting, n = 25)
      after 15 minutes of ex vivo incubation with phenoxybenzamine,
      verapamil/nitroglycerin solution, papaverine, or vehicle (control). Duration of
      action was assessed by measuring responses to vasoconstrictors in antispasmodic
      pretreated and control rings at intervals through 5 hours. RESULTS:
      Verapamil/nitroglycerin solution reduced vasoconstriction in response to
      epinephrine, angiotensin II, prostaglandin F(2alpha), and phenylephrine but its
      effect had almost completely waned after 5 hours. Phenoxybenzamine prevented
      vasoconstriction in response to epinephrine, dopamine, and phenylephrine, with
      its effect lasting at least 5 hours. Papaverine had limited antispasmodic
      efficacy and prevented vasoconstriction in response to potassium (60 mmol/L) and
      phenylephrine for only 1 hour at the longest. CONCLUSIONS:
      Verapamil/nitroglycerin solution has a broad efficacy against a range of
      vasoconstrictors but a limited duration of action. Papaverine has the shortest
      duration of action. Phenoxybenzamine is an effective agent with a prolonged
      duration of action, specifically preventing catecholamine mediated vasospasm of
      radial artery conduits.

PMID- 14688691
TI  - Insulin-induced improvement of postischemic recovery is abolished by inhibition
      of protein kinase C in rat heart.
AB  - OBJECTIVE: We demonstrated earlier that postischemic addition of insulin improves
      recovery of function in isolated rat heart by phosphatidylinositol 3-kinase.
      Activation of phosphatidylinositol 3-kinase before ischemia improves recovery of
      the heart after ischemia through protein kinase C. We tested whether protein
      kinase C activation is required for the positive inotropic effect of insulin
      during reperfusion. METHODS: Isolated working rat hearts were perfused with Krebs
      Henseleit buffer containing [2-(3)H]glucose (5 mmol/L, 0.05 microCi/mL) plus
      oleate (0.4 mmol/L) and were subjected to 15 minutes of global ischemia followed
      by 35 minutes of reperfusion with or without insulin (1 mU/mL). We measured
      cardiac power, glucose uptake, and tissue metabolites. The protein kinase C
      inhibitor chelerythrine (5 micromol/L) was added either at the beginning of the
      experiment or together with insulin. Experiments were repeated under normoxic
      conditions. RESULTS: Cardiac power before ischemia was 9.63 to 12.4 mW. Insulin
      improved recovery of power after ischemia (96.3% +/- 10.8% versus 65.7% +/-
      3.79%, P <.05). This effect was abolished by chelerythrine (55.3% +/- 6.49%).
      However, chelerythrine given at reperfusion did not block insulin's effect on
      recovery (101.0% +/- 4.25%, P <.05). Postischemic glucose uptake was not
      increased by insulin (3.07 +/- 0.32 before, 3.45 +/- 0.34 micromol/min/gdw after
      ischemia, not significant) and was not affected by chelerythrine (3.01 +/- 0.26
      before, 3.29 +/- 0.32 micromol/min/gdw after ischemia, not significant). Under
      normoxic conditions, chelerythrine did not influence insulin's effects on glucose
      uptake or power. CONCLUSION: The results suggest that (1) insulin's effect on
      recovery is dependent on ischemia-induced protein kinase C activation, (2) the
      activity of protein kinase C during reperfusion may not be important for this
      effect of insulin, and (3) protein kinase C plays no role in insulin's effect on
      glucose uptake under normoxic or postischemic conditions.

PMID- 14688692
TI  - Leukocyte-depleted terminal blood cardioplegia provides superior myocardial
      protective effects in association with myocardium-derived nitric oxide and
      peroxynitrite production for patients undergoing prolonged aortic crossclamping
      for more than 120 minutes.
AB  - OBJECTIVES: This study was designed to examine the myocardial protective effect
      of leukocyte-depleted terminal blood cardioplegia in association with nitric
      oxide and peroxynitrite production, especially for patients undergoing prolonged
      aortic crossclamping. METHODS: Fifty-four patients (34 men, 20 women, mean age
      56.7 +/- 12.7 years) undergoing aortic valve replacement were randomly allocated
      to one of two groups; group LDTC (n = 27) received 10 minutes of leukocyte
      depleted terminal blood cardioplegic solution, and group CONT (n = 27) served as
      controls. Each group was subdivided into 2 groups: aortic crossclamping for less
      than 120 minutes in groups LDTC-S (n = 13) and CONT-S (n = 14); aortic
      crossclamping for 120 minutes or more in groups LDTC-L (n = 14) and CONT-L (n =
      13). RESULTS: After aortic unclamping, group LDTC-L showed higher incidence of
      spontaneous defibrillation (78.6% vs 30.8%, P =.0213), higher plasma nitrate +
      nitrite in the coronary sinus effluent (32.5 +/- 4.1 vs 28.7 +/- 3.0 micromol/L,
      P =.0013), lower differences between coronary sinus effluent and arterial blood
      in the percentage ratio of nitrotyrosine to tyrosine (myocardium-derived
      peroxynitrite; 2.987% +/- 0.576% vs 3.951% +/- 0.952%, P =.0036), and plasma
      polymorphonuclear-elastase (113.9 +/- 21.3 vs 155.5 +/- 41.6 microg/L, P =.0029)
      and malondialdehyde (2.75 +/- 0.67 vs 4.02 +/- 0.96 micromol/L, P =.0005) than
      group CONT did. Postoperatively, group LDTC-L showed lower human-heart fatty acid
      binding protein (111.4 +/- 25.2 vs 156.4 +/- 38.6 IU/L, P =.0013), lower creatine
      kinase-muscle and brain (19.2 +/- 4.7 vs 24.8 +/- 6.5 IU/L, P =.0120), and
      smaller requirement of catecholamine (5.44 +/- 2.29 vs 8.45 +/- 3.42 microg x kg(
      1) x min(-1), P =.0122). There were no significant differences in these
      parameters between groups LDTC-S and CONT-S. CONCLUSIONS: This study demonstrated
      that leukocyte-depleted terminal blood cardioplegia provided superior myocardial
      protective effects and regulated myocardial-derived nitric oxide and
      peroxynitrite production only for patients undergoing aortic crossclamping for
      more than 120 minutes. The results suggest that prolonged aortic crossclamping
      deteriorates the tolerance to leukocyte-mediated myocardial injury accompanied by
      endothelial dysfunction associated with nitric oxide and peroxynitrite
      production.

PMID- 14688693
TI  - The Cox maze III procedure for atrial fibrillation: long-term efficacy in
      patients undergoing lone versus concomitant procedures.
AB  - BACKGROUND: For the last decade, the Cox maze III procedure has been available
      for the treatment of atrial fibrillation. It is unknown whether the operation has
      similar efficacy in patients with lone atrial fibrillation compared with that in
      patients with atrial fibrillation associated with coronary, valve, or congenital
      heart disease. This study examined the long-term outcome of patients who
      underwent this procedure either as a lone operation or as a concomitant
      procedure. METHODS: From 1988 to 2001, 198 patients underwent a Cox maze III
      procedure; 112 were lone operations, and 86 were concomitant procedures. Major
      complications included renal failure, reoperation for bleeding, mediastinitis,
      stroke, and balloon pump insertion. Follow-up was performed by means of mail and
      telephone questionnaires with both the patients and their cardiologists. All
      patients who had any history of arrhythmia or who were taking medication had
      their rhythm documented by means of electrocardiography. RESULTS: The lone
      operation group was significantly younger (51.3 +/- 10.5 vs 58.8 +/- 9.9 years)
      and had a higher male/female ratio (4:1 vs 2:1). There was no difference in
      operative mortality between groups (1.8% vs 1.2%). At a follow-up of 5.4 +/- 2.9
      years, 96.6% (172/178) of all patients were free of atrial fibrillation. There
      was no difference between the lone operation and concomitant procedure groups
      (95.9% vs 97.5%). CONCLUSION: The Cox maze III procedure has equivalent operative
      risk and long-term efficacy in patients undergoing both lone operations and
      concomitant procedures. The Cox maze III procedure remains the standard against
      which alternative procedures for atrial fibrillation must be judged.

PMID- 14688694
TI  - Can particulate extraction from the ascending aorta reduce neurologic injury in
      cardiac surgery?
AB  - OBJECTIVE: This study examined whether extraction of particulate emboli using
      intra-aortic filtration could decrease neurologic outcomes. METHODS: Patients (N
      = 582) were enrolled in a prospective, controlled study and alternately assigned
      to the therapy arm (n = 304; intra-aortic filtration) or control arm (n = 278).
      Preoperative, procedural, and postoperative data were collected. Neurologic
      examinations included the National Institutes of Health Stroke Scale, Glasgow
      Coma Scale, and memory tests. Investigators administering neurologic tests were
      blinded to the study arm. By the use of logistic regression and propensity
      matching, composite neurologic outcomes (transient ischemic attack, stroke,
      delirium, coma, and memory deficit) were evaluated. RESULTS: Patients in the
      filter group experienced a lower incidence of adverse neurologic outcomes than
      patients in the control group (4.3% vs 11.9%) (P <.001). There were significantly
      less transient ischemic attacks (0% vs 1.4%), delirium (3.0% vs 6.5%), and memory
      deficit (1.3% vs 6.2%). There were fewer strokes in the filter group compared
      with the control group (0.7% vs 2.2%), although the sample size was too small for
      a significant finding. Both groups experienced 1 coma outcome. The use of a
      filter was associated with an adjusted odds ratio of 0.375, implying that a
      patient who does not receive a filter is 2.7 times more likely to experience an
      adverse neurologic event. Logistic modeling also demonstrated that there are
      increasing chances of poor neurologic outcome with increasing age. The model
      indicates that there may be an increasing protective benefit from the filter with
      increasing age, although the interaction was not significant. CONCLUSIONS: The
      extraction of particulate emboli using intra-aortic filtration resulted in
      decreased neurologic outcomes.

PMID- 14688695
TI  - Inflammatory response to cardiac bypass in ewe fetuses: effects of steroid
      administration or continuous hemodiafiltration.
AB  - OBJECTIVES: We sought to investigate the effectiveness of glucocorticoid
      administration or continuous venovenous hemodiafiltration on endothelin and
      corticotropin-releasing factor release or clearance during prolonged fetal
      cardiac bypass and on the overall performance of fetuses. METHODS: Circulating
      endothelin 1, 2, and 3 and corticotropin-releasing factor levels were measured in
      fetal ewes during a 60-minute cardiac bypass period performed with an inline
      axial flow pump. Blood samples were collected before, during, and 90 minutes
      after cardiac bypass. Animals were divided into 4 groups. The betamethasone group
      (n = 6) received maternal treatment with 12 mg of betamethasone 1 and 2 days
      before the experiment. The methylprednisolone group (n = 5) received fetal
      treatment with 40 mg/kg intravenous methylprednisolone at the beginning of
      cardiac bypass. The continuous venovenous hemodiafiltration group (n = 4)
      underwent continuous venovenous hemodiafiltration with a 0.3-m(2) polysulfone
      filter during cardiac bypass. The final group was the control group (n = 4).
      RESULTS: Maternal steroid pretreatment failed to decrease endothelin or
      corticotropin-releasing factor production when compared with levels in the
      control animals. Fetal treatment with methylprednisolone produced a significant
      decrease in endothelin 2 production during cardiac bypass (P <.02) and endothelin
      1 production at the end of the experiment (P <.02). Continuous venovenous
      hemodiafiltration blocked completely the increase of endothelin and corticotropin
      releasing factor levels during cardiac bypass (P <.02), which was maintained 90
      minutes after cardiac bypass. Acid-base balance was preserved during cardiac
      bypass by the continuous venovenous hemodiafiltration but worsened after
      disconnection of the extracorporeal circuit, whereas animals treated with
      methylprednisolone had better pH, Paco(2), and bicarbonate levels by the end of
      the experiment. The overall tolerance of the procedure was better in the
      continuous venovenous hemodiafiltration group during cardiac bypass and in the
      methylprednisolone group at the end of the experiment. CONCLUSIONS: Continuous
      venovenous hemodiafiltration provides sustained stability of endothelin levels
      during fetal cardiac bypass. This technique might help, in association with fetal
      steroid treatment, to contain the inflammatory response leading to postbypass
      placental dysfunction.

PMID- 14688696
TI  - Conditioned blood reperfusion markedly enhances neurologic recovery after
      prolonged cerebral ischemia.
AB  - OBJECTIVES: To determine whether controlled reperfusion using conditioned
      leukodepleted blood can substantially limit cerebral reperfusion injury following
      prolonged ischemia. METHODS: Eighteen pigs (25-35 kg) underwent 90 minutes of
      hypothermic circulatory arrest (19 degrees C) to produce brain ischemia. At the
      start of rewarming, 10 pigs received uncontrolled reperfusion with unmodified
      (normal) blood. The other 8 pigs underwent 10 minutes of controlled reperfusion
      by selectively perfusing both common carotid arteries with blood passed through a
      CoBRA filter. This filter conditions the blood by removing white blood cells,
      platelets, and attenuating complement. Two other pigs underwent cooling and
      rewarming only (controls) without ischemia. Neurologic assessment was done using
      neurologic deficit scoring (0 = normal, 500 = brain death), and jugular venous
      samples were obtained for biochemical analysis postreperfusion. RESULTS: There
      were no statistical differences in hemodynamics between groups. At 6 hours
      postanesthesia, all animals receiving normal blood were substantially
      neurologically impaired. At 24 hours, they all had abnormal positioning and all
      but 1 were unable to sit or stand (neurologic score 124 +/- 19). In contrast,
      nonischemic controls and pigs receiving conditioned blood reperfusion showed only
      minor neurologic deficits at 6 hours, and at 24 hours all were considered normal
      (neurologic scores 0 and 6 +/- 5; P <.005 vs uncontrolled reperfusion). Compared
      with pigs receiving normal blood reperfusion, oxygen free radical formation
      (conjugated dienes 1.70 +/- 0.03 vs 1.60 +/- 0.02 Abs 240 nm; P <.05 vs
      uncontrolled reperfusion), and endothelin-1 release (2.12 +/- 0.09 vs 1.84 +/-
      0.06 pg/mL; P <.05 vs uncontrolled reperfusion) were also significantly lower in
      animals receiving conditioned blood. CONCLUSIONS: Following prolonged cerebral
      ischemia, reperfusion injury is avoided by delivering conditioned blood, which is
      devoid of white cells, platelets, and membrane attack complex. These results
      suggest that this modality is clinically useful in situations where the brain is
      subjected to prolonged ischemia.

PMID- 14688697
TI  - A new device for beating heart bipolar radiofrequency atrial ablation.
AB  - OBJECTIVE: A technique for mimicking left atrial atriotomies using an ablation
      device that can be deployed without cardiopulmonary bypass has been developed.
      METHODS: In 12 healthy large (35-50 kg) adult pigs, maze-like ablation lesions
      were directly applied to the left atrial epicardium on the beating heart. The
      ablation device is irrigated, with a bipolar "hemostat" morphology, utilizing
      radiofrequency energy. Prior to and after ablation, left atrial electromechanical
      properties were measured during sinus rhythm in the latest 5 pigs using
      percutaneous endocardial catheter electromechanical mapping and intracardiac
      echocardiography. Pathologic analysis was performed acutely. RESULTS: All
      ablation lesions demonstrated conduction block along their entire course. Global
      left atrial conduction time (49.4 +/- 8.8 milliseconds before vs 58.8 +/- 9
      milliseconds after) and pattern were not significantly altered. Although a
      significant amount (17.12% +/- 9%) of myocardium was either ablated or
      electrically isolated, ablation was not associated with significant alterations
      in global left atrial mechanics (left atrium ejection fraction 19% before vs 17%
      after; pulmonary vein peak flow velocity 1.22 m/s before vs 1.38 m/s after; peak
      mitral inflow velocity 2.34 m/s before vs 2.64 m/s after), mitral valve function,
      nor left ventricular function. There was no evidence of atrial thrombus
      formation. Transmurality was achieved in most lesions with no evidence of
      charring or barotrauma. CONCLUSIONS: Utilizing this ablation device, atrial
      lesions similar to the left component of the Maze procedure were deployed with
      uniform success in a beating heart without cardiopulmonary bypass or atriotomy
      and without adverse effects on left atrial electromechanics.

PMID- 14688698
TI  - Exhaled carbon monoxide and inducible heme oxygenase expression in a rat model of
      postperfusion acute lung injury.
AB  - OBJECTIVE: Expression of inducible heme oxygenase has been shown to be increased
      in various visceral inflammatory disorders, which may confer a protective role.
      The purpose of our study was to determine whether the expression of inducible
      heme oxygenase was up-regulated within lungs in a rat model of extracorporeal
      circulation. METHODS: Wistar rats underwent either a partial femoro-femoral
      extracorporeal circulation in normothermia for 3 hours (n = 5) or a sham
      procedure (n = 5). Exhaled carbon monoxide concentration was monitored with an
      infrared analyzer. After the rats were killed, lungs were harvested for
      determination of heme oxygenase activity and inducible heme oxygenase expression
      (by Western blot and immunohistochemistry). Lung injury was also assessed by
      arterial blood gas analysis and microscopic study. RESULTS: Extracorporeal
      circulation was responsible for a lung injury characterized by decreased arterial
      blood oxygen saturation and typical morphologic findings (marked alveolar
      neutrophil infiltration; interstitial edema). Exhaled carbon monoxide
      concentration remained stable throughout the experiment in all sham rats, whereas
      it increased after extracorporeal circulation (from 0.16 +/- 0.05 ppm at baseline
      to 0.7 +/- 0.2 ppm at end of experiment; P =.0001). Pulmonary heme oxygenase
      activity and inducible heme oxygenase content (assessed by Western blot) were
      increased within lungs of rats that underwent extracorporeal circulation.
      Immunohistochemistry revealed that the expression of inducible heme oxygenase was
      mainly localized to inflammatory cells. CONCLUSIONS: Post-extracorporeal
      circulation acute lung injury in rats was associated with an increased expression
      of inducible heme oxygenase, the functional significance of which remains to be
      determined.

PMID- 14688699
TI  - Preoperative use of enoxaparin is not a risk factor for postoperative bleeding
      after coronary artery bypass surgery.
AB  - BACKGROUND: The purpose of this study was to determine whether the use of low
      molecular-weight heparin before coronary artery bypass surgery would be
      associated with an increase in bleeding and use of blood products after the
      operation. METHODS: Sixty-four patients (48 men and 16 women) aged 64 +/- 10
      years who were undergoing primary coronary artery bypass surgery were
      prospectively studied. Forty-one patients were treated with either subcutaneous
      enoxaparin 1 mg/kg twice daily (n = 21; enoxaparin group) or intravenous heparin
      (n = 20; heparin group). Patients received the last dose of enoxaparin 8.7 +/-
      0.75 hours (range, 8-10 hours) before skin incision. Heparin was stopped before
      transfer to the operating room. An additional 23 consecutive patients who
      received neither enoxaparin nor heparin served as controls (n = 23). Anti-factor
      Xa activity, a measure of enoxaparin and heparin activity, was measured at the
      start of the operation in all patients. RESULTS: There was no perioperative
      mortality. The length of stay and frequency of postoperative complications were
      similar between groups. Preoperative anti-factor Xa activity was present only in
      the enoxaparin group (0.43 +/- 0.25 IU/mL). Chest tube drainage at 24 hours was
      553 +/- 160 mL, 532 +/- 140 mL, and 587 +/- 230 mL for the enoxaparin, heparin,
      and control groups, respectively (P =.48). There was no difference among groups
      in the amount of blood products transfused. CONCLUSIONS: Enoxaparin
      administration more than 8 hours before coronary artery bypass surgery is not
      associated with increased postoperative bleeding or blood product transfusion.

PMID- 14688700
TI  - Subcellular distribution of protein kinase C isozymes during cardioplegic arrest.
AB  - BACKGROUND: On the basis of the hypothesis that cardioplegia-associated
      myocardial depression was due to activation of protein kinase C, we examined
      whether specific protein kinase C isozymes would translocate to a cellular
      fraction containing myofilaments. METHODS: Isolated rat hearts were perfused with
      Krebs-Ringer bicarbonate buffer for 30 minutes and arrested with 4 degrees C St
      Thomas No. 2 cardioplegic solution for 0 to 120 minutes (n = 5 per group). The 3
      fractions of the left ventricle tissue represented the myofibrillar/nuclear
      fraction (P1), membranes (P2), and cytosol (supernatant). The distributions of
      protein kinase C isozymes alpha, delta, epsilon, and eta were examined after
      separation by electrophoresis, immunoblotting/chemiluminescence, and
      densitometry. RESULTS: A significant increase in protein kinase C-delta in the P1
      fraction was detected after 5 minutes of cardioplegic arrest and remained
      increased for 60 minutes. Increases in P1 protein kinase C-alpha and -epsilon
      were seen transiently at 5 minutes, and protein kinase C-epsilon demonstrated a
      secondary increase in P1 at 30 to 60 minutes. There was also a significant
      relative increase in protein kinase C-alpha and protein kinase C-delta in the P2
      fraction after 60 minutes of cardioplegia. CONCLUSIONS: These data are consistent
      with our hypothesis that activation of protein kinase C isozymes is associated
      with altered myofilament function after cardioplegic arrest.

PMID- 14688701
TI  - C-reactive protein activates the nuclear factor-kappaB signal transduction
      pathway in saphenous vein endothelial cells: implications for atherosclerosis and
      restenosis.
AB  - OBJECTIVES: Elevated levels of C-reactive protein are one of the strongest
      prognostic factors in atherosclerosis. In addition to predicting vascular
      disease, C-reactive protein may directly facilitate the development of a
      proinflammatory and proatherosclerotic phenotype. Recent studies have
      demonstrated marked up-regulation of various adhesion molecules and inflammatory
      responses in endothelial cells subjected to C-reactive protein. The nuclear
      factor-kappaB signal transduction is known to play a key role in the expression
      of these proatherogenic entities. This study examines the direct effects of C
      reactive protein on nuclear factor-kappaB activation and related mechanisms in
      saphenous vein endothelial cells. METHODS: The activation of nuclear factor
      kappaB was determined by confocal microscopy assessing the nuclear localization
      of nuclear factor-kappaB in endothelial cells incubated with C-reactive protein
      (50 microg/mL) for 30 minutes and 3 hours. Cells not incubated with C-reactive
      protein were used as negative controls, and cells incubated with tumor necrosis
      factor-alpha (10 ng/mL) for 15 minutes were used as positive controls in all
      studies. The degradation of IkappaB-alpha and IkappaB-beta was assessed by
      Western blotting of the cell lysates obtained from cells incubated with human
      recombinant C-reactive protein (50 microg/mL) for 15 minutes, 30 minutes, and 1
      hour. RESULTS: Nuclear factor-kappaB nuclear translocation in endothelial cells
      increased significantly after 30 minutes of incubation with C-reactive protein (P
      <.01). Nuclear localization of nuclear factor-kappaB returned to baseline levels
      after 3 hours of incubation with C-reactive protein. Incubation with C-reactive
      protein resulted in degradation of IkappaB-alpha that was maximal at 30 minutes
      (P <.05). C-reactive protein showed no significant effect on IkappaB-beta
      degradation. CONCLUSIONS: These data demonstrate, for the first time, that C
      reactive protein activates the nuclear factor-kappaB signal transduction pathway
      in endothelial cells. Degradation of IkappaB-alpha, but not IkappaB-beta, seems
      to be the major pathway leading to nuclear factor-kappaB nuclear translocation
      and activation induced by C-reactive protein. These data support the concept that
      C-reactive protein, at concentrations known to predict diverse vascular insults,
      directly facilitates a proinflammatory and proatherosclerotic phenotype through
      activation of nuclear factor-kappaB. These data have important implications for
      saphenous vein atherosclerosis in patients with elevated C-reactive protein
      levels.

PMID- 14688702
TI  - Pharmacologic inhibition of intracellular caspases after myocardial infarction
      attenuates left ventricular remodeling: a potentially novel pathway.
AB  - OBJECTIVE: Myocyte death occurs by necrosis and caspase-mediated apoptosis in the
      setting of myocardial infarction. In vitro studies suggest that caspase
      activation within myocytes causes contractile protein degradation without
      inducing cell death. Thus, caspase activation may evoke left ventricular
      remodeling through 2 independent processes post-myocardial infarction. However,
      the effects of caspase activation on left ventricular geometry post-myocardial
      infarction remain unclear. This project applied broad-spectrum caspase inhibition
      to a chronic porcine model of myocardial infarction. METHODS: Coronary snares and
      sonomicrometry crystals in remote and area-at-risk regions were placed in pigs (n
      = 22, 34 kg). Geometric measurements at end diastole and end systole, including
      left ventricular area by echocardiography and interregional distance by
      sonomicrometry, were obtained at baseline. Coronary occlusion was instituted for
      60 minutes, followed by reperfusion and repeated geometric measurements at 7
      days, including left ventriculography. At reperfusion, pigs were randomized to
      saline (n = 12) or caspase inhibition (n = 10, IDN6734, 2 mg/kg intravenously,
      then 2 mg x kg x h for 24 hours) at a dose that achieved desired plasma
      concentrations (790 +/- 142 ng/mL) as predicted by prior pharmacokinetic studies.
      RESULTS: Infarct size and 24-hour troponin-I values were not significantly
      different between the saline and caspase inhibition groups (51% +/- 8% vs 42% +/-
      6% and 189 +/- 20 ng/mL vs 152 +/- 26 ng/mL, respectively, P >.10). At 7 days,
      end-diastole volume was increased in both groups compared with reference control
      values (47 +/- 1 mL, P <.05), but it was decreased with caspase inhibition (72 +/
      4 mL) compared with saline (84 +/- 4 mL, P <.05). Similarly, end-diastole and
      end-systole areas increased by 32% +/- 3% and 81% +/- 16% in the saline group but
      were attenuated with caspase inhibition (19% +/- 3% and 31% +/- 10%,
      respectively, P <.05). End-diastole interregional distance increased by 30% +/-
      7% in the saline group but was attenuated with caspase inhibition (12% +/- 5%, P
      <.05). CONCLUSION: Despite equivalent degrees of myocardial injury, caspase
      inhibition reduced post-myocardial infarction left ventricular remodeling as
      evidenced by multiple, independent assessments of left ventricular dilation.
      Thus, caspase activation alters left ventricular geometry in the absence of
      significant effects on myocardial injury.

PMID- 14688703
TI  - A comparative analysis of positron emission tomography and mediastinoscopy in
      staging non-small cell lung cancer.
AB  - OBJECTIVES: Positron emission tomography has been demonstrated to improve the
      detection of distant metastases in patients with lung cancer. This study compares
      the efficacy of PET to mediastinoscopy in mediastinal staging of patients with
      non-small cell lung cancer. METHODS: Between May 1995 and May 2000, positron
      emission tomography was performed on 1988 patients with known or suspected non
      small cell lung cancer at Duke University Medical Center. Cervical
      mediastinoscopy was subsequently performed in patients without demonstrable
      evidence of distant metastases. The efficacy of mediastinal staging was analyzed
      by comparing the prospective results of positron emission tomography with the
      histopathologic results of mediastinoscopy by nodal station. RESULTS: In this
      study 202 patients with non-small cell lung cancer (116 of whom were male)
      underwent mediastinoscopy after positron emission tomography. Of the 65 patients
      with positive results of positron emission tomography, only 29 patients had
      positive results of mediastinoscopy in the corresponding nodal station. Of the
      137 patients with negative results of positron emission tomography, 16 patients
      were demonstrated to have N2 or N3 disease. The sensitivity, specificity,
      positive and negative predictive values, and accuracy for positron emission
      tomography were 64.4%, 77.1%, 44.6%, 88.3%, and 74.3%, respectively. Histologic
      findings in patients with non-small cell lung cancer and false-positive results
      of mediastinal positron emission tomography included granulomatous inflammation,
      sinus histiocytosis, and silicosis. CONCLUSIONS: Positron emission tomography
      neither confirms nor excludes involvement of the mediastinum in patients with non
      small cell lung cancer. Cervical mediastinoscopy with lymph node biopsy remains
      the criterion standard for mediastinal staging.

PMID- 14688704
TI  - Fluorodeoxyglucose positron emission tomography improves preoperative staging of
      resectable lung metastasis.
AB  - OBJECTIVE: F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is now
      a procedure of proven clinical value in the staging of primary lung cancer. This
      study evaluated the role of PET in the preoperative assessment of resectable lung
      metastases. METHODS: Eighty-six patients with previously treated malignancy and
      proven or suspected lung metastases, deemed resectable at computed tomography
      scan, were investigated with 89 preoperative PET procedures. Primary tumor sites
      were: gastrointestinal in 32 cases, sarcoma in 13, urologic in 14, breast in 8,
      head and neck in 7, gynecologic in 5, thymus in 5, other in 5. Seventy lung
      resections were performed in 68 patients of whom only 54 proved to be lung
      metastasis, 7 were primary lung tumors, and 9 were benign lesions. RESULTS: In 19
      cases (21%) lung surgery was excluded on the basis of PET scan results due to
      extrapulmonary metastases (11 cases), primary site recurrence (2), mediastinal
      adenopathy (2), or benign disease (4). All mediastinal node metastases (7 cases)
      were detected by PET with a sensitivity, accuracy, and negative predictive value
      for mediastinal staging of 100%, 96%, and 100%, respectively, versus 71%, 92%,
      and 95% of the computed tomography scan. In the group of patients who underwent
      lung resection, PET sensitivity for detection of lung metastasis was 87%.
      CONCLUSIONS: PET scan proved to be a valuable staging procedure in patients with
      clinically resectable lung metastasis and changed the therapeutic management in a
      high proportion of cases.

PMID- 14688705
TI  - Pleural lavage cytology in non-small cell lung cancer: lessons from 1000
      consecutive resections.
AB  - OBJECTIVE: Intraoperative pleural lavage cytology for lung cancer has not been
      widely accepted. The prognostic significance of this procedure has yet to be
      intensively analyzed because the reports published thus far have involved small
      patient populations. We therefore performed a large prospective trial of pleural
      lavage cytology to elucidate its importance. METHODS: Cytologic status of pleural
      lavage fluid before any manipulation of the lung was examined in 1000 consecutive
      patients with non-small cell lung cancer but no pleural effusion who underwent
      tumor resection. RESULTS: Forty-five (4.5%) of 1000 patients had positive
      cytologic findings. Positive cytologic findings were observed more frequently in
      patients with adenocarcinoma, advanced stage, higher involvement of lymph nodes,
      pleural involvement of the tumor, lymphatic permeation, vascular invasion, high
      level of serum carcinoembryonic antigen, and male sex. The survival rate for 5
      years was 28% in patients with positive findings and 67% in patients with
      negative findings (P <.0001). Among 587 patients with stage I disease, 13 (2.2%)
      had positive findings, and their 5-year survival was 43%, which was significantly
      poor compared with that of patients with negative findings (81%, P =.0009).
      Multivariable analysis demonstrated that pleural lavage cytology was an
      independent prognostic determinant (P =.0290). Regarding the recurrence pattern
      in patients with positive findings, distant metastases (19/45 [42.2%]) were
      observed more frequently rather than local recurrences (19/45 [22.2%]).
      CONCLUSIONS: Cytologic status of pleural lavage fluid immediately after
      thoracotomy, an independent significant prognostic factor, constitutes valuable
      information to detect patients at a high risk of recurrence. Therefore cytology
      should be performed at the time of curative resection for non-small cell lung
      cancer.

PMID- 14688706
TI  - Development of a canine model of pulmonary emphysema and imaging of the
      emphysematous lung with infrared thoracoscopy.
AB  - BACKGROUND: The surgeon must use the results of preoperative computed tomography
      findings and scintigraphic studies to make a subjective decision during lung
      volume reduction surgery with regard to the best incision line. OBJECTIVES: Our
      purpose was to develop an objective and real-time method of detecting areas of
      pulmonary emphysema by using infrared thoracoscopy. METHODS: Pulmonary emphysema
      was developed in various lobes of the lung in the dog by injecting porcine
      pancreatic elastase through the bronchi. One month after the injection, chest
      computed tomography and lung biopsy were performed. Infrared thoracoscopic study
      was then performed to reveal the presence of the emphysematous lung tissue.
      Simultaneously, indocyanine green was injected intravenously, and the time taken
      for each type of lung tissue to stain blue was measured. RESULTS: Chest computed
      tomography and histologic examinations revealed pulmonary emphysema-like areas in
      the porcine pancreatic elastase-injected lung. The computed tomography numbers of
      the porcine pancreatic elastase-injected lung tissue, normal lung tissue, and the
      tracheal lumen were -868.8 +/- 18.6, -752.2 +/- 32.5, and -1013 +/- 27.1,
      respectively. There were significant differences between the porcine pancreatic
      elastase-injected lung and the normal lung (P <.0001). The time for staining to
      begin was 10.7 +/- 4.8 seconds for normal lung tissue and 25.8 +/- 9.4 seconds
      for the emphysematous tissue; the onset of staining emphysematous lung tissue was
      significantly delayed (P =.003). CONCLUSIONS: We developed a successful canine
      model of pulmonary emphysema by injecting porcine pancreatic elastase. Infrared
      thoracoscopic examination revealed that the staining of emphysematous lung using
      indocyanine green injection was significantly greater than of normal lung.

PMID- 14688707
TI  - The immunologic role of thymectomy in the treatment of myasthenia gravis:
      implication of thymus-associated B-lymphocyte subset in reduction of the anti
      acetylcholine receptor antibody titer.
AB  - BACKGROUND AND PURPOSE: Thymectomy is generally accepted as the major option of
      treatment for myasthenia gravis. To elucidate the biological role of thymectomy
      in the treatment of myasthenia gravis, the immunologic characteristics of the
      thymus was studied in association with the postoperative kinetics of the anti
      acetylcholine receptor antibody titer. MATERIALS AND METHODS: Thirty-four
      patients with nonthymomatous myasthenia gravis who had positive anti
      acetylcholine receptor antibody titer and undergoing extended thymectomy were
      subjected to the study. Reduction of anti-acetylcholine receptor antibody titer
      was evaluated in terms of the proportion of anti-acetylcholine receptor antibody
      titer at 1 year after thymectomy to that before the operation. The numbers of B
      lymphocytes (CD19(+) cells) and the germinal center B lymphocytes
      (CD19(+)CD38(high) cells) present in 1 g of the thymic tissue were calculated by
      flow cytometry. RESULTS: The proportion of anti-acetylcholine receptor antibody
      titer at 1 year after thymectomy ranged from 27.5% to 150%. The numbers of B
      lymphocytes and the germinal center B lymphocytes in 1 g of the thymic tissue
      ranged from 0.19 x 10(6)/g to 162.8 x 10(6)/g and from 0.09 x 10(6)/g to 33.4 x
      10(6)/g, respectively. The proportion of anti-acetylcholine receptor antibody
      titer at 1 year after thymectomy had a significant inverted correlation with the
      number of B lymphocytes (P =.002) as well as that of the germinal center B
      lymphocytes (P =.007). CONCLUSION: Effectiveness of thymectomy was dependent on
      predominance of B lymphocytes and the germinal center B lymphocytes in the
      thymus, suggesting that one of the biological roles of thymectomy in the
      treatment of myasthenia gravis is removing the thymus-associated germinal
      centers.

PMID- 14688708
TI  - Modified reperfusion and ischemia-reperfusion injury in human lung
      transplantation.
AB  - OBJECTIVE: Ischemia-reperfusion injury remains a major cause of mortality and
      morbidity in clinical lung transplantation. Interaction of activated leukocytes
      with injured graft endothelial cells participates in the development of ischemia
      reperfusion injury. We sought to determine if modification of the reperfusate
      (with depletion of leukocytes and alteration of its composition) would decrease
      the incidence of ischemia-reperfusion injury in human lung transplantation when
      compared with whole blood reperfusion in a historical group of patients. METHODS:
      Between June 1999 and July 2001, 23 adult patients undergoing lung
      transplantation consented to modified reperfusion. After implantation, a catheter
      was inserted into the main or individual pulmonary arteries, and modified
      reperfusate was administered at a pressure less than 20 mm Hg. The modified
      reperfusate was depleted of leukocytes, supplemented with nitroglycerin, adjusted
      for pH and calcium level, and enriched with aspartate, glutamate, and dextrose.
      After 10 minutes of modified reperfusion, the removal of pulmonary artery clamp
      or weaning of cardiopulmonary bypass was performed per usual protocol. Age- and
      diagnosis-matched historical patients served as the control group. Ischemia
      reperfusion injury was defined as Pao(2)/Fio(2) < 150 with diffuse infiltrate on
      the radiograph in absence of other causes. RESULTS: There was no difference in
      donor age or oxygenation indices, recipient age, the number of patients requiring
      cardiopulmonary bypass, ischemia time, and recipient oxygenation indices between
      the modified reperfusate group and the control group. However, none of the
      patients in the modified reperfusate group developed ischemia-reperfusion injury
      in contrast to 5 patients in the control group (P <.05). The early survival in
      the modified reperfusate group was 96% versus 81% in the control group (P = NS).
      CONCLUSION: This study suggests that modification of the reperfusate content
      decreases the incidence of ischemia-reperfusion injury in human lung
      transplantation when compared with whole blood reperfusion in a historical group
      of patients. Modified reperfusate may allow acceptance of marginal lungs and
      expansion of the donor pool.

PMID- 14688709
TI  - Optimal management when unsuspected N2 nodal disease is identified during
      thoracotomy for lung cancer: cost-effectiveness analysis.
AB  - OBJECTIVES: Whether to proceed with lung resection when N2 nodal disease is
      identified at the time of thoracotomy for lung cancer is controversial. A
      decision analysis model was developed to address this question. METHODS: A meta
      analysis was performed on data from reports published between 1990 and 2002
      evaluating survival for (1) patients who were treated by initial resection for
      clinically unsuspected N2 nodal disease (initial resection) and (2) survival for
      patients undergoing resection after neoadjuvant therapy for N2 nodal disease (no
      initial resection). Hospital cost data for surgery were derived from our
      institution, and cost data for chemotherapy and radiation therapy were obtained
      from current literature. A decision model was developed to compare initial
      resection to no initial resection from the perspective of the medical center
      using survival, quality-adjusted life years survival, and cost-effectiveness as
      outcomes. RESULTS: The no initial resection option provided better median
      survival (2.1 versus 1.7 years), quality-adjusted life years (1.8 versus 1.3),
      and cost-effectiveness, with an incremental cost-effectiveness ratio of 17,119
      dollars/quality-adjusted life year. Outcomes were influenced by survival
      estimates for each treatment option. CONCLUSIONS: When N2 nodal disease is
      discovered during thoracotomy, the approach of delaying resection until after
      neoadjuvant therapy provides the best survival and is more cost-effective. This
      is likely due to the beneficial effects of neoadjuvant therapy and the exclusion
      of patients with more aggressive disease from the surgical candidate pool.

PMID- 14688710
TI  - Results of the American College of Surgeons Oncology Group Z0050 trial: the
      utility of positron emission tomography in staging potentially operable non-small
      cell lung cancer.
AB  - OBJECTIVES: The American College of Surgeons Oncology Group undertook a trial to
      ascertain whether positron emission tomography with 18F-fluorodeoxyglucose could
      detect lesions that would preclude pulmonary resection in a group of patients
      with documented or suspected non-small cell lung cancer found to be surgical
      candidates by routine staging procedures. METHODS: A total of 303 eligible
      patients registered from 22 institutions underwent positron emission tomography
      after routine staging (computed tomography of chest and upper abdomen, bone
      scintigraphy, and brain imaging) had deemed their tumors resectable. Positive
      findings required confirmatory procedures. RESULTS: Positron emission tomography
      was significantly better than computed tomography for the detection of N1 and
      N2/N3 disease (42% vs 13%, P =.0177, and 58% vs 32%, P =.0041, respectively). The
      negative predictive value of positron emission tomography for mediastinal node
      disease was 87%. Unsuspected metastatic disease or second primary malignancy was
      identified in 18 of 287 patients (6.3%). Distant metastatic disease indicated in
      19 of 287 patients (6.6%) was subsequently shown to be benign. By correctly
      identifying advanced disease (stages IIIA, IIIB, and IV) or benign lesions,
      positron emission tomography potentially avoided unnecessary thoracotomy in 1 of
      5 patients. CONCLUSIONS: In patients with suspected or proven non-small cell lung
      cancer considered resectable by standard staging procedures, positron emission
      tomography can prevent nontherapeutic thoracotomy in a significant number of
      cases. Use of positron emission tomography for mediastinal staging should not be
      relied on as a sole staging modality, and positive findings should be confirmed
      by mediastinoscopy. Metastatic disease, especially a single site, identified by
      positron emission tomography requires further confirmatory evaluation.

PMID- 14688711
TI  - Simultaneous progression of oxidative stress and angiogenesis in malignant
      transformation of Barrett esophagus.
AB  - BACKGROUND: Oxidative stress and angiogenesis are important elements in the
      pathogenesis of inflammatory diseases and cancer. Our aim was to evaluate the
      role of both and of antioxidant capacity in the metaplasia-dysplasia
      adenocarcinoma sequence in Barrett epithelium. METHODS: In mucosal specimens from
      59 patients grouped as having symptomatic gastroesophageal reflux disease,
      Barrett epithelium, or adenocarcinoma in the esophagus, plus controls, we
      measured myeloperoxidase activity, superoxidase dismutase activity, glutathione
      content, and total aromatic DNA adducts. To evaluate blood vessel densities and
      angioarchitecture, we used immunohistochemistry and a modified whole-mount
      technique. Sections were stained with endothelium-specific markers and smooth
      muscle cell actin. RESULTS: The reflux disease-metaplasia-carcinoma sequence
      revealed progressively increased oxidative stress (increased myeloperoxidase
      activity), decreased antioxidant capacity (glutathione content), and simultaneous
      formation of DNA adducts. Pooled data show a negative correlation between
      glutathione content and DNA adducts (-0.28; P =.05). This sequence was also
      characterized by increased intensity in microvessels and an increasing percentage
      of immature blood vessels. In addition, the whole-mount technique offered 3
      dimensional evidence that the rich new vascular bed is highly abnormal, with
      repeated twists, bends, or turns, even in nonmalignant Barrett esophagus.
      CONCLUSIONS: Increased oxidative stress, decreased antioxidant capacity, and a
      negative correlation between glutathione content and DNA adduct formation
      indicate a link between oxidative stress and malignant transformation of Barrett
      epithelium. Simultaneously, this transformation acquires angiogenic capacity,
      strong neovascularization, and abnormal angioarchitecture.

PMID- 14688712
TI  - Extracardiac total cavopulmonary connection using a tissue-engineered graft.
AB  - OBJECTIVE: Extracardiac and lateral tunnel total cavopulmonary connection are
      currently 2 major options for patients with a single ventricle physiology.
      However, each procedure has some disadvantages over the other. We developed a new
      technique of extracardiac total cavopulmonary connection using a tissue
      engineered graft to overcome some of the disadvantages previously associated with
      both the extracardiac and lateral tunnel procedures. METHODS: Between February
      2001 and October 2002, 8 patients underwent an extracardiac total cavopulmonary
      connection using a tissue-engineered graft in our institution. Collected bone
      marrow cells (1 x 10(8) mononucleocytes) from a patient (approximately 1-4 mL/kg
      body weight) were seeded onto a biodegradable scaffold composed of
      polycaprolactone-polylactic acid copolymer reinforced with woven polylactic acid.
      After a 2- to 4-hour cultivation, the seeded scaffold was implanted as an
      extracardiac conduit during the total cavopulmonary connection operation.
      RESULTS: There were no hospital or late deaths. At a mean follow-up of 13.4
      months (range 4-25 months), all patients are alive and asymptomatic with no need
      for repeat surgery. A postoperative catheter examination or computed tomography
      showed all tissue-engineered grafts to be patent and revealed no stenosis,
      obstruction, or aneurysmal change in the 8 patients. CONCLUSION: We believe that
      extracardiac total cavopulmonary connection using a tissue-engineered graft has
      the potential to overcome some of the disadvantages previously associated with
      extracardiac or lateral tunnel total cavopulmonary connection. However, an
      extended follow-up period is required to clarify the long-term clinical outcome
      for the tissue-engineered graft.

PMID- 14688713
TI  - A novel technique for light delivery through branched or bent anatomic
      structures.
AB  - OBJECTIVE: Photodynamic therapy is an effective cancer treatment, but light
      delivery constraints currently limit its application to superficial, easily
      visualized tumors. The goal of this study was to determine whether it would be
      possible to manipulate the optical properties of irregularly shaped anatomic
      structures for the purpose of light delivery. Such a technique could potentially
      expand the role of photodynamic therapy to treat tumors currently viewed as
      inaccessible to visible light. METHODS: Ex vivo sheep tracheas and lungs were
      filled with substances of varying refractive indices. The effects on transmission
      of visible light of a known wavelength introduced into the proximal lumen of the
      organs were studied. Data were collected with naked-eye observation, standard
      photography, charge-coupled device imaging, and direct light measurement.
      RESULTS: Filling a lung or trachea with a liquid possessing a refractive index
      higher than that of tissue dramatically increases the ability to deliver light
      around bends and through a branched network. CONCLUSION: It is possible to
      manipulate the optical properties of an ex vivo organ for the purpose of enhanced
      light delivery.

PMID- 14688714
TI  - Atherosclerotic involvement of the radial artery in patients with coronary artery
      disease and its relation with midterm radial artery graft patency and endothelial
      function.
AB  - BACKGROUND: The radial artery has recently been proposed as an alternative
      arterial conduit for surgical myocardial revascularization. This study was
      conceived to evaluate the degree of atherosclerotic involvement of the radial
      artery in patients with coronary artery disease and the eventual influence of a
      subtle degree of preoperative atherosclerosis on the midterm results of radial
      artery grafts. METHODS AND RESULTS: The intima-media thickness of the radial
      artery, common carotid artery, and internal thoracic artery was evaluated in 42
      coronary artery disease patients and in 26 control patients. All radial arteries
      were then used for myocardial revascularization; 30 patients submitted to control
      angiography after 5 years. The mean intima-media thickness was 0.92 +/- 0.22 mm
      for the common carotid artery, 0.54 +/- 0.16 mm for the internal thoracic artery,
      0.55 +/- 0.11 mm for the radial artery in coronary artery disease patients versus
      0.79 +/- 0.14 mm, 0.52 +/- 0.11 mm, and 0.56 +/- 0.09 mm, respectively, in
      control patients (P =.001 only for the common carotid artery). No correlation was
      found between the intima-media thickness of the carotid, internal thoracic, and
      radial artery. No correlation was found between the preoperative intima-media
      thickness of the radial artery and the midterm patency and endothelial-mediated
      vasodilating capacity of radial artery grafts. CONCLUSION: In coronary artery
      disease patients, radial artery atherosclerotic involvement is more frequent than
      that of the gold standard internal thoracic artery but still by far less severe
      than that of the common carotid artery. The early atherosclerotic signs often
      observed in the radial artery do not seem to have the potential to influence
      radial artery graft patency and endothelial function.

PMID- 14688715
TI  - Factors affecting saphenous vein graft patency: clinical and angiographic study
      in 1402 symptomatic patients operated on between 1977 and 1999.
AB  - BACKGROUND: The purpose of this study was to find the preoperative and
      intraoperative factors that affect vein graft patency. METHODS: A total of 3715
      graft angiograms in 1607 patients were studied for recurrence of angina. The
      preoperative patient characteristics and intraoperative variables were
      prospectively collected from patients who had primary coronary artery bypass
      grafting during the period from 1977 to 1999. A total of 1339 (83%) patients were
      male, with a mean age of 59 years. The mean period from operation to reangiogram
      was 99 months. The saphenous vein was grafted to the left anterior descending
      artery in 557 (15%), to the diagonal artery in 669 (18%), to the obtuse marginal
      artery in 1300 (35%), to the right coronary artery in 409 (11%), and to the
      posterior descending artery in 780 (21%) cases. Graft failure was defined as
      >or=80% stenosis. RESULTS: During the course of the study, 2266 (61%) grafts were
      patent, and 1449 (39%) had failed. The patient variables that significantly
      reduced graft patency were a younger age (P <.001) and an ejection fraction <30%
      (P =.047). Operative variables associated with reduced graft patency were small
      coronary artery diameter (P <.001), large conduit diameter (P =.001), and the
      coronary artery grafted (lowest patency in the right coronary artery and maximum
      patency in the left anterior descending artery territory; P =.002). The interval
      from operation to repeat angiogram (P <.001, with 78% patent at 1 year, 78% at 5
      years, 60% at 10 years, and 50% at 15 years) and the year in which the operation
      was performed (more recent operations had better patency; P <.001) significantly
      affected graft patency. CONCLUSIONS: Saphenous vein graft patency improved over
      the course of the study. The best results were obtained in older patients with
      good left ventricular function. Large-caliber arteries on the left system, when
      grafted with a small-diameter vein, were associated with the best outcome.

PMID- 14688716
TI  - Acute type A aortic dissection complicated by aortic regurgitation: composite
      valve graft versus separate valve graft versus conservative valve repair.
AB  - OBJECTIVE: To clarify the merits of various surgical approaches, we studied the
      outcome after composite valve graft versus separate valve and graft replacement
      versus conservative valve treatment with replacement of the ascending aorta in
      patients with acute type A aortic dissection complicated by aortic regurgitation.
      METHODS: Between 1967 and 1999, 123 patients (mean age 56 +/- 15 years) underwent
      composite valve graft replacement (n = 21), separate valve and graft replacement
      (n = 20), or conservative valve treatment (n = 82 [commissural resuspension in
      46]); follow-up averaged 6.5 years (95% complete). RESULTS: The 30-day, 1-year,
      and 6-year survival estimates of 85% +/- 4%, 79% +/- 5%, and 69% +/- 5% (+/-1
      standard error of mean), respectively, after conservative valve treatment were
      similar to 86% +/- 8%, 81% +/- 9%, and 65% +/- 16%, respectively, with composite
      valve graft replacement and better (but insignificantly so) than 70% +/- 10%, 70%
      +/- 10%, and 45% +/- 11%, respectively, with separate valve and graft
      replacement. The 6-year freedom from proximal reoperation was 95% +/- 3%, 89% +/-
      10%, and 100% in conservative valve graft, separate valve and graft, and
      composite valve graft subgroups, respectively (P = not significant). Cox
      regression multivariable analysis identified that previous sternotomy (hazard
      ratio [or e(beta)] 95% confidence interval 1.4-10.9, P =.006), hypertension (0.99
      2.9, P =.05), cardiac tamponade (1.1-4.0, P =.03), and stroke (1.7-7.0, P =.001)
      increased the hazard of death. No factors predicting a higher likelihood of late
      proximal reoperation were identified. CONCLUSIONS: In patients with acute type A
      aortic dissection and aortic regurgitation, there was no significant difference
      in overall survival or reoperation rates among these surgical approaches. We try
      to save the valve whenever possible unless the aortic root is pathologically
      dilated (eg, Marfan syndrome or annuloaortic ectasia) or destroyed by the
      dissection process, when composite valve graft or valve-sparing aortic root
      replacement is indicated.

PMID- 14688717
TI  - Midterm results of edge-to-edge mitral valve repair without annuloplasty.
AB  - OBJECTIVE: Edge-to-edge mitral valve repair is usually performed in association
      with annuloplasty, with rare exceptions. We retrospectively analyzed the results
      of ringless edge-to-edge repair, particularly in view of minimally invasive and
      percutaneous approaches. METHODS: From November 1993 to December 2001, 81
      patients underwent edge-to-edge mitral repair without associated annuloplasty.
      The cause was degenerative in most patients. In 32 patients the annulus was
      severely calcified. Type I lesions were present in 6 patients, type II lesions in
      60 patients, and type III lesions in 15 patients. A double-orifice repair was
      done in 69 patients, and paracommissural repair was done in 12 patients. In 5
      patients edge-to-edge repair was used as a rescue procedure. RESULTS: There were
      3 hospital and 4 late deaths, for a 4-year survival of 85% +/- 6.7%. At latest
      follow-up, 63 patients were in New York Heart Association classes I or II, and 9
      patients were in classes III or IV. Nine patients required reoperation (89% +/-
      3.9% overall freedom from reoperation at 4 years). Annular calcification was
      associated with a greater reoperation rate (77% +/- 22% vs 95% +/- 4.6% freedom
      from reoperation, P =.03). Intraoperative water testing and postrepair
      transesophageal echocardiography predicted late failure. Only 1 of 42 patients
      required reoperation in the follow-up period when annular calcification,
      rheumatic disease, or rescue procedure were not present as risk factors.
      CONCLUSIONS: Our data confirm overall suboptimal results of the edge-to-edge
      technique when annuloplasty is not added to the repair. Annular calcification,
      rheumatic cause, and edge-to-edge repair done as a rescue procedure were
      associated with the worst outcome. Midterm results in selected patients encourage
      future developments in catheter-based edge-to-edge procedures.

PMID- 14688718
TI  - Laparoscopic omental flap for the treatment of major sternal wound infection
      after cardiac surgery.
AB  - BACKGROUND: The ideal reconstructive procedure after sternal debridement is still
      a matter of debate. The omentum might be theoretically preferable for its
      favorable properties, but it is seldom used because it entails the added trauma
      of a laparotomy. METHODS: Three female patients with severe osteomyelitis after
      myocardial revascularization underwent sternal debridement and filling of the
      defect with a laparoscopically prepared omental flap. Sternal wound closure was
      achieved as a single-stage procedure in 2 patients. The third patient had a
      poststernotomy septicemia and required a 2-stage procedure. The abdominal
      procedures were conducted through 3 operating 5-mm ports. Omental flaps were
      developed by complete separation from the transverse colon and lengthening by
      division of some anastomosing arteries between gastroepiploic vessels and
      Barkow's arcade. Thoracic transposition of the omentum was achieved through a 5
      cm diaphragmatic incision. The flaps were able to reach the base of the neck and
      fill the sternal defect in all patients. RESULTS: A smooth postoperative course
      was observed. Oral intake was started from day 2; sole oral nutrition was
      maintained from day 3 or 4. Optimal wound healing was observed with minimal or
      absent local discomfort. Minor transient paradoxical movements of the anterior
      chest wall disappeared within 1 month. Postoperative hospital stay was 9, 14, and
      14 days, respectively. CONCLUSIONS: Laparoscopic omentoplasty, compared with the
      open procedure, entails several advantages for the treatment of sternal
      osteomyelitis. The introduction of minimally invasive techniques may widen the
      indications for the use of the omentum in the treatment of major sternal wound
      infections.

PMID- 14688719
TI  - Decellularization of rat aortic valve allografts reduces leaflet destruction and
      extracellular matrix remodeling.
AB  - OBJECTIVES: Decellularization of aortic valve allografts in advance of
      transplantation is a promising approach to overcome immune-induced early graft
      failure. In this study the effects of in vitro cell extraction on extracellular
      matrix molecules and in vivo remodeling of decellularized aortic valves were
      investigated in a heterotopic aortic valve rat implantation model. METHODS: Rat
      aortic valve conduits were decellularized by a 2-step detergent-enzymatic
      extraction method involving sodium dodecyl sulfate in combination with RNase and
      DNase. Cellular and acellular allogeneic (2x, n = 4) and syngeneic valve grafts
      (2x, n = 3) were grafted infrarenally into the descending aorta for 21 days.
      Immunohistochemical techniques were used to study extracellular matrix
      constitution (elastin, collagen, fibronectin, and chondroitin sulfate) and
      cellular infiltration. RESULTS: The decellularization procedure resulted in a
      complete loss of all cellular structures from the entire valve conduit with
      minimal damage to the extracellular matrix. All transplanted cellular allografts
      became deformed, swollen, and acellular with major changes in extracellular
      matrix structure. The transplanted decellularized allografts, however, retained
      normal preserved valve leaflets comparable to transplanted cellular and acellular
      syngeneic grafts. With the exception of cellular syngeneic grafts, all other
      grafts showed retrovalvular thrombi. CONCLUSIONS: Damage to the valves caused by
      decellularization technique is much less than the damage caused by the
      recipient's immune response. In vitro removal of viable cells in (cryopreserved)
      homografts may decrease graft failure. Seeding with autologous or major
      histocompatibility complex-matched donor endothelial cells will be necessary to
      diminish damage induced by an absent blood-tissue barrier.

PMID- 14688720
TI  - Carbon dioxide embolism during endoscopic saphenous vein harvesting in coronary
      artery bypass surgery.
AB  - OBJECTIVES: Our objectives were to determine the incidence and severity and the
      time course of the CO(2) embolism during endoscopic saphenous vein harvesting
      with CO(2) insufflation in coronary artery bypass surgery with transesophageal
      echocardiography monitoring. METHODS: Four hundred three consecutive patients
      scheduled for off-pump coronary artery bypass grafting surgery or femoral-to
      popliteal artery bypass grafting surgery were prospectively studied. Multiplane
      transesophageal echocardiography with a new transgastric view was used to monitor
      CO(2) bubbles in the inferior vena cava and hepatic vein. RESULTS: CO(2)
      embolisms occurred in 17.1% of patients. Minimal, moderate, and massive CO(2)
      embolisms occurred in 13.1%, 3.5%, and 0.5%, respectively. The occurrence of
      moderate and massive CO(2) embolisms was frequently associated with the surgical
      manipulation of branches of saphenous veins. No significant risk factors were
      identified in multiple logistic regression analysis. CONCLUSION: The incidence of
      significant CO(2) embolism during endoscopic saphenous vein harvesting with CO(2)
      insufflation procedures was more than 4%. Continuous transesophageal
      echocardiographic monitoring of the CO(2) bubbles in the inferior vena cava is
      essential in early detection and can help to prevent the development of
      significant CO(2) embolisms in these patients.

PMID- 14688721
TI  - The long-term outcome of patients with coronary disease and atrial fibrillation
      undergoing the Cox maze procedure.
AB  - BACKGROUND: A significant number of patients presenting for coronary
      revascularization have chronic atrial fibrillation. Although the Cox maze III
      procedure is the gold standard for the surgical treatment of this arrhythmia, few
      of these patients undergo atrial fibrillation operations at the time of their
      coronary bypass grafting. This study examined the long-term outcome of patients
      with ischemic heart disease who underwent the Cox maze procedure at our
      institution. METHODS: From 1990 to 2002, 47 patients undergoing operations for
      ischemic heart disease underwent a concomitant Cox maze III procedure. All
      patients underwent coronary bypass grafting, and 7 (15%) patients underwent
      coronary bypass grafting plus a mitral valve repair. Follow-up was performed by
      means of mail and telephone questionnaires with both the patients and their
      cardiologists. All patients who had any history of arrhythmia or who were taking
      medications had their rhythm documented by electrocardiogram. RESULTS: The mean
      age of these patients was 62 +/- 8 years, with a marked male predominance (45 men
      and 2 women). Twenty-eight (60%) of the patients had paroxysmal atrial
      fibrillation, and the remainder had persistent arrhythmias. The mean duration of
      atrial fibrillation was 7.6 +/- 6.5 years. The operative mortality in this series
      was 2%. Nine (19%) patients required postoperative pacemakers. At last follow-up
      (mean of 5.7 +/- 3.3 years), 98% of patients were free of atrial fibrillation.
      CONCLUSION: The Cox maze III procedure has a low operative mortality and
      excellent long-term efficacy in patients with ischemic heart disease. These data
      suggest a more widespread use of this procedure in these patients.

PMID- 14688722
TI  - Twenty-year experience with the St Jude Medical mechanical valve prosthesis.
AB  - BACKGROUND: We have prospectively followed all adult St Jude Medical mechanical
      valve recipients at the Medical University of South Carolina since the initial
      implant in January 1979 and now present our 20-year experience. METHODS: We
      prospectively followed 837 valve recipients (aortic valve replacement; n = 478;
      mitral valve replacement; n = 359) from January 1979 to December 2000 at 12-month
      intervals. RESULTS: Ages ranged from 19 to 84 years. Follow-up averaged (mean +/-
      standard deviation) 7 +/- 5 years (98% complete). Patients were in New York Heart
      Association class III or IV in 77% (aortic valve replacement) and 89% (mitral
      valve replacement) preoperatively. A 19-mm valve was implanted in 15.5% of aortic
      valve replacement patients. Coronary bypass was required in 31% of aortic valve
      replacements and 20% of mitral valve replacements. Operative mortality was 17/478
      (3.6%) in aortic valve replacement and 19/359 (5.3%) in mitral valve replacement,
      and multivariable predictors were 19-mm valve size, 3 or more coronary bypass
      grafts, and New York Heart Association class IV for aortic valve replacement and
      New York Heart Association class IV and age for mitral valve replacement.
      Actuarial survivorship at 10 and 20 years was 57% +/- 3% and 26% +/- 5% for
      aortic valve replacement and 61% +/- 3% and 39% +/- 4% for mitral valve
      replacement. Multivariable predictors of late death were African-American
      ethnicity, New York Heart Association class III or IV, coronary bypass, and age
      for aortic valve replacement and New York Heart Association class III or IV,
      coronary bypass, and age for mitral valve replacement. For aortic valve
      replacement, effective orifice area was univariately (P =.002) but not
      multivariately (P =.378) predictive of late death. Structural valve deterioration
      was not observed. For aortic valve replacement, actuarial freedom (at 10 and 20
      years) from reoperation was 93% +/- 1% and 90% +/- 2%; thromboembolism, 82% +/-
      3% and 68% +/- 8%; bleeding events, 77% +/- 3% and 66% +/- 6%; prosthetic valve
      endocarditis, 94% +/- 1% and 94% +/- 1%; valve-related mortality, 94% +/- 2% and
      86% +/- 4%; and valve-related mortality or morbidity, 58% +/- 3% and 32% +/- 8%.
      For mitral valve replacement, actuarial freedom (at 10 and 20 years) from
      reoperation was 96% +/- 1% and 90% +/- 3%; thromboembolism, 77% +/- 3% and 59% +/
      7%; bleeding events, 86% +/- 2% and 65% +/- 8%; prosthetic valve endocarditis,
      98% +/- 1% and 96% +/- 2%; valve-related mortality, 89% +/- 0.2% and 74% +/- 8%;
      and valve-related mortality or morbidity, 63% +/- 3% and 29% +/- 7%. CONCLUSIONS:
      After 2 decades of observation with close follow-up, the St Jude Medical
      mechanical valve continues to be a reliable prosthesis.

PMID- 14688723
TI  - Gender and outcomes after coronary artery bypass grafting: a propensity-matched
      comparison.
AB  - OBJECTIVE: Our objective is to determine whether gender is a marker or a causal
      influence for poor outcomes after coronary revascularization. METHODS: Propensity
      modeling techniques were used to investigate whether gender adversely impacts
      outcomes after coronary revascularization. A parsimonious explanatory model was
      developed by bootstrap bagging with variable selection from 64 baseline and 37
      operative variables. Propensity scores were calculated from a logistic model that
      included the parsimonious model and additional baseline variables. Greedy
      matching techniques were applied to match female and male patients to the nearest
      propensity scores. Comparisons were made among the propensity-matched women and
      men. RESULTS: Of the 15,597 patients undergoing isolated coronary artery bypass
      graft surgery, only 26% of the 3596 women were matched on propensity scores with
      men. Distribution of covariates among the matched pairs was, on average, equal.
      Postoperative mortality (P =.76), neurologic morbidity (global deficit P =.07,
      focal deficit P =.51), infection (sepsis P =.88), mediastinitis (P =.18), renal
      failure (P =.84), intra-aortic balloon pump usage (P =.61), and reoperation for
      bleeding (P =.10) were similar among women and men. Occurrence of Q-wave
      myocardial infarction (P = <.01), postoperative inotropic usage (P = <.01), and
      prolonged ventilatory support (P =.02) were more common in women compared with
      propensity-matched men. CONCLUSIONS: The preoperative profiles of women and men
      are markedly different. Propensity matching women and men was difficult, because
      only 26% of women were able to be matched with men. However, in well-matched
      patients, female gender was not associated with increased mortality and had
      minimal impact on morbidity after coronary artery bypass grafting.

PMID- 14688724
TI  - Gender profiling in coronary artery bypass grafting.
AB  - OBJECTIVE: Although women are reported to be at increased risk of poor outcome
      after coronary artery bypass grafting, female gender may simply be a marker of a
      high-risk profile. Therefore, the objective of this study was to characterize the
      difference between the female and male profiles of patients presenting for
      coronary artery bypass grafting. METHODS: From January 1993 to June 2002, 15,597
      patients underwent isolated coronary artery bypass grafting at a single
      institution. Multivariable logistic regression was used to develop a model of
      female gender. RESULTS: Of 15,597 patients, 3596 (23%) were women. Eighteen
      variables were predictive of the female gender profile, including shorter
      stature, increased weight, more hypertension, insulin-treated diabetes mellitus,
      heart failure, and higher triglyceride and high-density lipoprotein cholesterol
      levels. Hematocrit, bilirubin, and creatinine values were lower in women compared
      with men. CONCLUSIONS: The preoperative profiles of women and men undergoing
      coronary artery bypass grafting are dissimilar. Statistical modeling techniques
      provide a unique perspective on the preoperative profile of the female patient,
      who is known to be at a higher risk undergoing coronary artery bypass grafting.

PMID- 14688725
TI  - Pentoxifylline is as effective as leukocyte depletion for modulating pulmonary
      reperfusion injury.
AB  - OBJECTIVE: Previous studies have suggested the amelioration of lung reperfusion
      injury when initial reperfusion is undertaken with leukocyte-depleted blood.
      Pharmacologic agents, such as pentoxifylline, are also effective, but no previous
      studies have demonstrated which is superior. We investigated these agents in a
      porcine model of left single-lung transplantation. METHODS: Donor lungs were
      preserved with modified Euro-Collins solution for a mean ischemic time of 18.6
      hours. Gas exchange, pulmonary vascular resistance, neutrophil elastase level,
      and free radical release (measured on the basis of malonaldehyde levels) were
      assessed over a 12-hour period. Group A (n = 5) was a control group with no
      interventions added. Group B was reperfused through an extracorporeal circuit
      incorporating a leukocyte-depleting filter for 30 minutes before conventional
      blood flow was restored. Group C was reperfused with the addition of intravenous
      pentoxifylline (2 mg x kg(-1) x h(-1)). RESULTS: Groups B and C were similar in
      terms of oxygenation, pulmonary vascular resistance, and free radical release.
      Group B displayed increased levels of neutrophil elastase. Both groups were
      superior with regard to these outcome measures compared with control group A.
      CONCLUSIONS: Pentoxifylline, when administered to recipient animals, attenuates
      reperfusion injury to a degree similar to that seen with leukocyte-depleted
      reperfusion. This technique is simple, safe, and as effective as using a more
      complex extracorporeal circuit incorporating a leukocyte-depleting filter to
      ameliorate acute lung injury.

PMID- 14688726
TI  - Rapamycin has no effect on fibrosis-associated gene expression or extracellular
      matrix accumulation when administered to animals with established or early
      allograft vasculopathy.
AB  - BACKGROUND: Most patients with functioning heart transplants have established and
      progressive chronic allograft vasculopathy, a fibroproliferative process for
      which there is no effective treatment. Coronary artery disease is characterized
      by histologic evidence of extracellular matrix accumulation (fibrosis). This
      study compares the effect of rapamycin administered to rats with established
      allograft vasculopathy on histologic indices of disease progression,
      extracellular matrix accumulation (fibrosis), and the expression of genes known
      to regulate extracellular matrix turnover in this model. METHODS: Lewis
      recipients of Fisher 344 rat thoracic to abdominal aorta transplants were
      administered rapamycin starting at 8, 12, and 16 weeks posttransplant or no
      treatment. Six grafts in each group were harvested at 24 weeks. Vascular
      remodeling and collagen accumulation (Sirius red) were measured by computerized
      histomorphometry of aortic sections. mRNA was extracted from frozen tissue, and
      the expression of fibrosis-associated genes was studied by means of
      semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS:
      Rapamycin had no effect on the progression of early or established allograft
      vasculopathy with regard to intimal thickening, remodeling, extracellular matrix
      accumulation, or profibrotic gene expression, regardless of the time commenced.
      CONCLUSION: The attenuation of the fibroproliferative response in rodents by
      rapamycin is not seen if the onset of rapamycin therapy is delayed.

PMID- 14688727
TI  - Ten-year follow-up in patients with combined heart and kidney transplantation.
AB  - BACKGROUND: Combined heart and kidney transplantation has been documented,
      although data regarding immunosuppression, rejection episodes, and graft or
      patient survival have not been detailed. We evaluated our experience and more
      than 10-year outcome with patients selected for combined heart and kidney
      transplantation. METHODS: Eight patients aged 29 to 59 years were selected for
      combined heart and kidney transplantation. The indications were end-stage heart
      disease and underlying renal pathology, or secondary renal insufficiency, or
      renal failure. Six patients were dialysis dependent before transplantation. There
      were 7 simultaneous procedures and 1 staged procedure. The heart was transplanted
      first in all cases. All patients were maintained after transplantation on
      azathioprine (2 mg x kg(-1) x d(-1)) and whole-blood monoclonal cyclosporine
      levels at greater than 200 microg/L; prednisone was not decreased to less than 10
      mg/d. RESULTS: Seven (87.5%) patients have survived a mean duration of 100.4
      months (range, 51-144 months), and each allograft has continued to function. The
      only death was due to pulmonary emboli and was not related to allograft rejection
      or failure. Only 4 cardiac and 4 kidney allograft rejections have occurred. Five
      patients have been free of kidney rejection, 1 patient has been rejection free
      for more than 8 years, and no patient has had simultaneous rejection.
      CONCLUSIONS: In select patients, combined heart and kidney transplantation can
      provide long-term graft function and patient survival. The low rates of rejection
      support our current approach to immunosuppression. Our experience indicates that
      end-stage failure of either heart or kidney does not necessarily preclude dual
      organ transplantation.

PMID- 14688728
TI  - Ventricular assist surprise: giant cell myocarditis or sarcoidosis?

PMID- 14688729
TI  - Intraparenchymal replacement of the left pulmonary artery with implantation of
      segmental arteries in a 26-year-old patient.

PMID- 14688730
TI  - Chondrosarcoma arising in the trachea: a case report and review of the
      literature.

PMID- 14688731
TI  - Videothoracoscopic extrapleural insertion of Walter Lorenz surgical bar for
      pectus excavatum.

PMID- 14688732
TI  - Total thoracoscopic pneumonectomy: indications and technical considerations.

PMID- 14688733
TI  - Intralobar sequestration in the middle-aged and elderly adult: recognition and
      radiographic evaluation.

PMID- 14688734
TI  - Staged dilation and stenting for long segmental tracheobronchial stenosis caused
      by tuberculosis.

PMID- 14688735
TI  - Multilocular tuberculous cyst of thymus gland.

PMID- 14688736
TI  - Cervical cannulation for resternotomy in pediatric patients.

PMID- 14688737
TI  - Axillary artery cannulation for extracorporeal membrane oxygenator support in
      adults: an approach to minimize complications.

PMID- 14688738
TI  - Left-sided cervical aortic arch aneurysm: case report.

PMID- 14688739
TI  - Mechanical support of the unrepaired postinfarction ventricular septal defect
      with the Abiomed BVS 5000 ventricular assist device.

PMID- 14688740
TI  - Urgent inferior vena cava replacement with an autologous pericardium tube graft.

PMID- 14688741
TI  - Foreign bodies expectorated through the pneumonectomy stump.

PMID- 14688742
TI  - Chronic and adjustable pulmonary artery banding: reflections on old knowledge.

PMID- 14688743
TI  - Lobar transplantation.

PMID- 14688744
TI  - Brachial artery cannulation.

PMID- 14688745
TI  - Medical resources and capital punishment.

PMID- 14688746
TI  - Bivalirudin as alternative to both danaparoid and heparin in off-pump coronary
      artery bypass grafting.

PMID- 14688747
TI  - Apical versus basal partial ventriculectomy.

PMID- 14688748
TI  - Study of warm perfusion rather than cardioplegia.

PMID- 14688749
TI  - Nickel allergy to the percutaneous patent foramen ovale occluder and subsequent
      systemic nickel allergy.

PMID- 14688750
TI  - Activated prothrombin complex concentrates and recombinant factor VIIa in the
      bleeding patient: are they appropriate and safe?

PMID- 14688751
TI  - A few critical aspects--and Achilles heels--of tissue engineering approaches to
      restore injured myocardium.

PMID- 14688752
TI  - Coagulation, fibrinolysis, and cell activation in patients and in shed
      mediastinal blood during coronary artery bypass grafting with a new heparin
      coated surface.

PMID- 14688753
TI  - Myogenesis after myocardial stem cell transplantation.

PMID- 14688754
TI  - Asymptomatic mitral valve incompetence: is there evidence for surgery?

PMID- 14688755
TI  - Esophageal perforation during left atrial radiofrequency ablation.

PMID- 14688756
TI  - Mentoring: to everything a season.

PMID- 14688757
TI  - Charting a course and course corrections: challenges in leadership.

PMID- 14688759
TI  - The Leadership Enhancement and Development (LEAD) Project for minority nurses (in
      the new millennium model).
AB  - This article describes the development of a model designed to enhance and develop
      minority nurses. Select literature on leadership and diversity are highlighted.
      Background information that was pertinent to the development of the model is
      provided, as well as some brief information on how the model is being used in an
      ongoing project.

PMID- 14688760
TI  - Participatory action research: the Indian Family Stories Project.
AB  - Community-based research projects are critically needed to reduce health
      disparities and ensure the delivery of health care that is culturally appropriate
      and relevant to families and communities. The purpose of this article is to share
      experiences and lessons learned from utilizing a participatory action approach in
      a series of five subprojects within the Indian Family Stories Project.
      Participatory action research (PAR) focuses on identifying community needs and
      designing action plans in partnership with the community. To effectively
      implement PAR projects, investigators need to: (a) Build and maintain strong,
      collaborative working relationships with a broad network of community
      representatives, (b) Secure funding that addresses community needs and provides
      mechanisms for giving back to the community, (c) Ensure that the project fits the
      particular cultural and community context, (d) Evaluate and adapt the project as
      needed, (e) Keep the community informed, (f) Develop sustainable community
      resources, and (g) Advocate on behalf of the community.

PMID- 14688761
TI  - Minimizing disincentives for collaborative research.
AB  - While collaborative research partnerships offer a number of advantages, the
      disincentives to collaboration which are present in the academic environment can
      be daunting and can result in failure unless they are explicitly and proactively
      addressed. Based on successful models of collaboration and a review of the
      literature, four disincentives to collaboration-increased requirements for time
      and communication, lack of clarity regarding leadership, need to share resources
      and revenue, and the problem of partners who do not fulfill their commitments-are
      discussed and strategies to minimize these disincentives are presented.

PMID- 14688767
TI  - Working Group on Health Services Research and Nursing established.

PMID- 14688763
TI  - Interactive voice response system (IVRS) in health care services.
AB  - Recent advances in telecommunications technology have created opportunities to
      enhance the quality of health care services through telehealth, the use of
      telecommunications and information technologies to deliver health care. However,
      the diverse technologies and applications encompassed by telehealth have tended
      to confuse discussions of the effectiveness of these programs. An interactive
      voice response system (IVRS) is a simple, yet effective telehealth application
      that improves access to health care by continuing care beyond the hospital
      setting, with specially tailored programs that are easily accessible to patients
      around the clock. Often described as a telephone connected to a "talking
      computer," an IVRS allows patient interaction for data collection or to deliver
      recorded telephone messages related to medication compliance or behavior
      modification. Despite easy access to touchtone telephone services and growing
      familiarity with IVRS, many health care providers are unaware of these programs.
      This paper reviews the infrastructure of IVRS technology and its uses in health
      care.

PMID- 14688762
TI  - The perceived value of certification by certified perioperative nurses.
AB  - We conducted this study to determine the perceived value of certification in
      perioperative nursing. Following development and pilot-testing, we mailed the 18
      item Likert-type instrument, the Perceived Value of Certification Tool (PVCT), to
      a sample of 2750 perioperative nurses who had earned the CNOR or CRNFA credential
      or both. A total of 1398 surveys were returned (50.8% response rate). Factor
      analysis extracted three factors, accounting for 61% of the variance: personal
      value, recognition by others, and professional practice. Internal consistency
      reliability testing (Cronbach's alpha) identified a standardized alpha of.924.
      Over 90% of respondents agreed or strongly agreed with statements about the value
      of certification related to feelings of personal accomplishment and satisfaction,
      validating specialized knowledge, indicating professional growth, attainment of a
      practice standard, personal challenge, and professional commitment, challenge,
      and credibility. These results are consistent with previously published
      literature on specialty certification in nursing.

PMID- 14688771
TI  - Whither podiatry?

PMID- 14688772
TI  - The zero-plus first metatarsal and its relationship to bunion deformity.
AB  - The relationship between first metatarsal length and hallux valgus (HV) deformity
      was examined. Retrospectively, 210 randomly selected radiographic files were
      reviewed between 1988 and 1993. The morbid population consisted of 110 feet with
      HV deformities. The control population consisted of 100 healthy feet (no
      deformity). Seventy-seven percent of the patients with HV deformity had a first
      metatarsal length that was equal to or longer than the second metatarsal. This
      was defined as a zero-plus first metatarsal. Only 28% of the control population
      had this same proportion in length. Thus, prevalence of zero-plus first
      metatarsal was significantly associated with HV formation (chi(2)(1) = 51.15, P
      <.001). The mean first metatarsal protrusion distance was significantly higher in
      the bunion population (+1.58 mm) than in the control patients (-2.05 mm) (P
      <.001). The distribution of head shape differed significantly between the
      patients with HV and control patients; patients with HV had predominantly round
      heads (91%) and the control patients had predominantly square and square with a
      ridge heads (80%) (chi(2)(2) = 107.7, P <.001). All zero-plus first metatarsals
      in the HV population had a round first metatarsal head. Only 7.1% of the control
      patients had a round head with a zero-plus metatarsal. There was a positive
      relationship between the protrusion distance of the first metatarsal and the
      severity of the intermetatarsal angle, particularly in those patients with
      intermetatarsal angles ranging from 13 degrees to 20 degrees (P <.01). It was
      concluded that a zero-plus first metatarsal is a significant etiologic factor in
      the development of bunion deformity and should be part of the preoperative
      evaluation.

PMID- 14688773
TI  - Intrinsic pedal musculature support of the medial longitudinal arch: an
      electromyography study.
AB  - Much of the work describing support of the medial longitudinal arch has focused
      on the plantar fascia and the extrinsic muscles. There is little research
      concerning the function of intrinsic muscles in the maintenance of the medial
      longitudinal arch. Ten healthy volunteer adults served as subjects for this
      study, which was approved by the University Investigational Review Board. The
      height of the navicular tubercle above the floor was measured in both feet while
      subjects were seated with the foot in a subtalar neutral position and then when
      standing in a relaxed calcaneal stance. Subtalar neutral was found by palpating
      for talar congruency. Recordings of muscle activity from the abductor hallucis
      muscle were performed while the subjects maintained a maximal voluntary
      contraction in a supine position by plantarflexing their great toes. An injection
      of lidocaine (1% with epinephrine) was then administered by a Board-certified
      orthopedic surgeon in the region of the tibial nerve, posterior and inferior to
      the medial malleolus. Measurements were repeated and compared by using a paired t
      test. After the nerve block, the muscle activity was 26.8% of the control
      condition (P =.011). This corresponded with an increase in navicular drop of 3.8
      mm. (P =.022). The observation that navicular drop increased when the activity of
      the intrinsic muscles decreased indicates that the intrinsic pedal muscles play
      an important role in support of the medial longitudinal arch.

PMID- 14688774
TI  - Comparison of pullout strength of small-diameter cannulated and solid-core
      screws.
AB  - The purpose of this study was to determine the difference in pullout strength
      between cannulated and solid-core small-diameter bone screws. Cannulated screws
      from different manufacturers were compared against solid-core screws with 2.0-mm,
      2.4-/2.5-mm, and 3.0-mm diameters. A synthetic material made to simulate
      bicortical bone was used as the test medium. The screws were extracted under
      servohydraulic control. There was no statistically significant difference between
      any of the cannulated and solid-core 2.0-mm screws used in this study (P <.05).
      In the 2.4-/2.5-mm screw tests, both of the cannulated screw designs had a
      significantly higher pullout strength when compared with the solid-core screw (P
      <.05). In the testing of 3.0-mm screw test, 1 of the cannulated screw designs
      showed a significantly higher pullout strength than the other cannulated and
      solid-core screws that were tested (P <.05). The results of this study suggest
      that small-diameter cannulated bone screws are similar in mechanical pullout
      strength to solid-core screws.

PMID- 14688775
TI  - Mechanical comparison of fixation techniques for the offset V osteotomy: a saw
      bone study.
AB  - Four different techniques for the fixation of an offset V bunionectomy were
      tested on solid-foam saw-bone models for the purpose of determining the strongest
      form of fixation for the osteotomy. Twenty identical models were placed into 4
      different groups. Groups varied as to the placement and caliber of fixation.
      Models were loaded with a servo-hydraulic testing machine until failure of
      fixation occurred. Video analysis was used to record the pattern of failure of
      the fixation. Failure occurred either distal to the first screw, through the
      first screw hole, between the 2 screws, through the second screw hole, or
      proximal to the second screw. The mean force to failure of the groups was group
      1, 58.1 N; group 2, 59.3 N; group 3, 64.0 N; and group 4, 105.66 N. There was a
      statistical significant difference between group 4 and the other 3 groups (F(1) =
      55.45, P < 0.05). There was no statistical difference between groups 1 to 3. In
      groups 1 to 3, 87% of the failures were through the distal screw hole, whereas
      the remaining 13% were through the proximal screw hole. In group 4, 60% of the
      failures were through the proximal screw hole and 40% were through the distal
      screw hole. It was concluded that, in this model, the strongest form of fixation
      for an offset V osteotomy was the 2.7-mm cortical screw placed distally with the
      proximal point of fixation being a threaded 0.062-inch Kirschner wire.

PMID- 14688776
TI  - Mechanical characteristics of the new BONE-LOK bi-cortical internal fixation
      device.
AB  - The purpose of this study was to evaluate the mechanical characteristics of a new
      and unique titanium compression anchor with BONE-LOK (Triage Medical, Inc,
      Irvine, CA) technology for compressive, bi-cortical internal fixation of bone.
      This device provides fixation through the use of a distal grasping anchor and an
      adjustable proximal collar that are joined by an axially movable pin and guide
      wire. The titanium compression anchor, in 2.0-, 2.7-, and 3.5-mm diameters, were
      compared with cortex screws (Synthes USA, Paoli, PA) of the same diameter and
      material for pullout strength in 20 lb/cu ft and 30 lb/cu ft solid rigid
      polyurethane foam; and for compression strength in 20 lb/cu ft foam. Retention
      strength of the collar was tested independently. The results showed significantly
      greater pullout strength of the 2.7-mm and 3.5-mm titanium compression anchor as
      compared with the 2.7-mm and 3.5-mm cortex screws in these test models. Pullout
      strength of the 2.0-mm titanium compression anchor was not statistically
      different in comparison with the 2.0-mm cortical screws. Compression strength of
      the titanium compression anchor was significantly greater than the cortical
      screws for all diameters tested. These differences represent a distinct advantage
      with the new device, which warrants further in vivo testing. Collar retention
      strength testing values were obtained for reference only and have no comparative
      significance.

PMID- 14688777
TI  - BIOPRO resurfacing endoprosthesis versus periarticular osteotomy for hallux
      rigidus: short-term follow-up and analysis.
AB  - Forty-four patients (47 feet) were enrolled in a prospective hallux rigidus
      study. A subjective evaluation, physical examination, and radiographic analysis
      were performed preoperatively and at a 1-year follow-up. Twenty patients (20
      feet) underwent a periarticular osteotomy, with 16 patients (16 feet) returning.
      Seven patients (9 feet) underwent a BIOPRO resurfacing endoprosthesis, with all
      patients returning. The subjective evaluation was based on a modified American
      Orthopaedic Foot and Ankle Society Hallux Metatarsophalangeal-Interphalangeal 100
      Point scale. The physical examination included first metatarsophalangeal joint
      range of motion. Radiographic analysis included the metatarsal protrusion
      distance, transverse plane angulation of the second digit, lateral talo-first
      metatarsal angle, sagittal plane relationship of the first and second
      metatarsals, and hallux equinus angle. Statistically significant differences
      between preoperative and postoperative values were found for the periarticular
      osteotomy group for the metatarsal protrusion distance (P =.000), transverse
      plane angulation of the second digit (P =.000), and lateral talo-first metatarsal
      angle (P =.015). No other statistically significant differences between the pre
      operative and post-operative values for either procedure group were found to
      exist. For this specific patient population the short-term results of surgical
      intervention for hallux rigidus, whether through a periarticular osteotomy or
      resurfacing endoprosthesis, provided subjective patient improvement and
      satisfaction, as well as, minimal increase in first metatarsophalangeal joint
      range of motion.

PMID- 14688778
TI  - Arthroscopic removal of a juxtaarticular osteoid osteoma of the talar neck.
AB  - The authors report a case of a 21-year-old woman with osteoid osteoma of the
      talar neck that was treated with arthroscopic resection. The nidus was removed in
      one piece with grasping forceps, and histopathologic findings confirmed the
      preoperative diagnosis of osteoid osteoma. Postoperatively, the patient was
      immediately relieved of ankle pain and there was no recurrence at the 1-year
      follow-up. If possible, the nidus should be removed without the use of a
      motorized instrument to ensure the correct histolologic diagnosis.

PMID- 14688779
TI  - True posterior dislocation of subtalar joint: a case report.
AB  - Posterior dislocation subtalar joint is rare and usually results from a high
      velocity injury. Previous reports of all complete posterior dislocations of the
      subtalar joint have had some degree of a rotational component. We report a case
      of a true complete posterior dislocation of subtalar joint with no rotation.

PMID- 14688780
TI  - Autoamputation of the foot caused by untreated gas gangrene: a case report.
AB  - Gas-producing diabetic foot infections are limb-threatening emergencies commonly
      encountered by foot and ankle surgeons. Appropriate treatment includes aggressive
      surgical debridement, parenteral antibiotics, and postoperative wound care. The
      authors present a unique case of a patient who refused treatment for a deep-space
      gas-producing infection, resulting in autoamputation of the foot. The authors
      also discuss the confusion surrounding the definition of gas gangrene.

PMID- 14688781
TI  - Maggot therapy for wound debridement in a traumatic foot-degloving injury: a case
      report.
AB  - A 43-year-old man was treated for a traumatic degloving injury to his foot with a
      transmetatarsal amputation and wound care because of the extensive soft tissue
      loss. After biweekly sharp debridements in the office for 4 weeks, very minimal
      skin ingrowth was noted. Maggot therapy was then implemented for a 48-hour
      treatment and a second treatment for 72 hours to help reduce excessive fibrosis
      and to painlessly debride the tissues to expose the granular base. Daily dressing
      changes for the next 6 weeks successfully allowed complete wound closure without
      any additional interventions. During the follow-up course, no complications were
      encountered and the patient has returned to ambulation with the use of a cane.

PMID- 14688782
TI  - Hypermobility of the first ray: a critical review of the literature.
AB  - The authors provide a detailed review of the available literature regarding first
      ray sagittal plane direction and range of motion with special emphasis on whether
      or not hypermobility of the first ray can truly be supported as a definable
      clinical entity. They also describe a novel clinical test for assessing sagittal
      plane instability of the first ray. The authors believe that this test, when
      combined with previously defined clinical tests, helps to identify those few
      patients that would benefit from an arthrodesis procedure of the medial pillar of
      the foot for the treatment of the hallux valgus deformity.

PMID- 14688783
TI  - Minicondylar plates: an alternative method of fixation for first ray procedures.

PMID- 14688784
TI  - Use of a hybrid kickstand external fixator for pressure relief after soft-tissue
      reconstruction of heel defects.

PMID- 14688789
TI  - Chemoradiation for upper aerodigestive tract cancer: balancing evidence from
      clinical trials with individual patient recommendations.

PMID- 14688790
TI  - Late-G1 cyclin-CDK activity is essential for control of cell morphogenesis in
      budding yeast.
AB  - The accurate spatial and temporal coordination of cell polarization with DNA
      replication and segregation guarantees the fidelity of genetic transmission. Here
      we report that in Saccharomyces cerevisiae, a build-up or burst of G1 cyclin
      dependent kinase (CDK) activity through activation of the cyclin genes CLN1,2 and
      PCL1,2 is essential for cell morphogenesis, but not for other events associated
      with the G1-S-phase transition, including DNA replication. Strains lacking a
      burst of late-G1 cyclin-CDK activity (LG1C(-)) undergo a catastrophic
      morphogenesis and halt the nuclear cycle at the morphogenesis checkpoint in G2
      phase. Consistent with a role in morphogenesis, the Pho85 G1 cyclins Pcl1 and
      Pcl2 show a unique pattern of localization to sites of polarized cell growth, and
      strains lacking PCL1 and PCL2 show genetic interactions with the cell polarity
      GTPase Cdc42, its regulators and downstream effectors. Our data suggest that
      inability to assemble a septin ring and localize the GTP exchange factor Cdc24 at
      the incipient bud site may be the primary morphogenetic defects in LG1C-depleted
      cells. We conclude that a burst of late G1 cyclin-CDK activity is essential for
      establishing cell polarity and development of the cleavage apparatus.

PMID- 14688791
TI  - An NDPase links ADAM protease glycosylation with organ morphogenesis in C.
      elegans.
AB  - In the nematode Caenorhabditis elegans, the gonad acquires two U-shaped arms
      through the directed migration of its distal tip cells (DTCs), which are located
      at the tip of the growing gonad arms. A member of the ADAM (a disintegrin and
      metalloprotease) family, MIG-17, regulates directional migration of DTCs: MIG-17
      is synthesized and secreted from the muscle cells of the body wall, and diffuses
      to the gonad where it is required for DTC migration. The mig-23 mutation causes
      defective migration of DTCs and interacts genetically with mig-17. Here, we
      report that mig-23 encodes a membrane-bound nucleoside diphosphatase (NDPase)
      required for glycosylation and proper localization of MIG-17. Our findings
      indicate that an NDPase affects organ morphogenesis through glycosylation of the
      MIG-17 ADAM protease.

PMID- 14688792
TI  - Nitric oxide switches on glycolysis through the AMP protein kinase and 6
      phosphofructo-2-kinase pathway.
AB  - After inhibition of cytochrome c oxidase by nitric oxide, astrocytes maintain
      energy production by upregulating glycolysis--a response which does not seem to
      be available to neurons. Here, we show that in astrocytes, after inhibition of
      respiration by nitric oxide, there is a rapid, cyclic GMP-independent increase in
      the activity of 6-phosphofructo-1-kinase (PFK1), a master regulator of
      glycolysis, and an increase in the concentration of its most powerful positive
      allosteric activator, fructose-2,6-bisphosphate (F2,6P(2)). In neurons, nitric
      oxide failed to alter F2,6P(2) concentration or PFK1 activity. This failure could
      be accounted for by the much lower amount of 6-phosphofructo-2-kinase (PFK2, the
      enzyme responsible for F2,6P(2) biosynthesis) in neurons. Indeed, full activation
      of neuronal PFK1 was achieved by adding cytosol from nitric oxide-treated
      astrocytes. Furthermore, using the small interfering RNA (siRNA) strategy, we
      demonstrated that the rapid activation of glycolysis by nitric oxide is dependent
      on phosphorylation of the energy charge-sensitive AMP-activated protein kinase,
      resulting in activation of PFK2 and protection of cells from apoptosis. Thus the
      virtual absence of PFK2 in neurons may explain their extreme sensitivity to
      energy depletion and degeneration.

PMID- 14688793
TI  - Mutant Frizzled 4 associated with vitreoretinopathy traps wild-type Frizzled in
      the endoplasmic reticulum by oligomerization.
AB  - nt signalling pathways regulate cell proliferation, cell fate and morphogenetic
      movements. Here, we demonstrate that the Frizzled (Fz) family of Wnt receptors,
      similarly to G-protein-coupled receptors (GPCRs), form specific homo- and hetero
      oligomers. Two lines of evidence suggest that oligomerization occurs in the
      endoplasmic reticulum: first, a mutant allele of Fz4, encoding a truncated
      protein that is retained in the endoplasmic reticulum, is linked to the autosomal
      dominant retinal degenerative disease, familial exudative vitreoretinopathy
      (FEVR). We show that this mutant form of Fz4 oligomerizes with wild-type Fz4,
      retains it in the endoplasmic reticulum and inhibits its signalling. Second, a
      derivative of Fz1 targeted to the endoplasmic reticulum traps wild-type Fz1 in
      the endoplasmic reticulum and blocks its signalling. These data support the
      hypothesis that oligomerization of mutant and wild-type Fz proteins occurs in the
      endoplasmic reticulum and may explain the genetic dominance of this FEVR allele.

PMID- 14688794
TI  - The transmembrane protein XFLRT3 forms a complex with FGF receptors and promotes
      FGF signalling.
AB  - Fibroblast growth factors (FGFs) signal through high-affinity tyrosine kinase
      receptors to regulate a diverse range of cellular processes, including cell
      growth, differentiation and migration, as well as cell death. Here we identify
      XFLRT3, a member of a leucine-rich-repeat transmembrane protein family, as a
      novel modulator of FGF signalling. XFLRT3 is co-expressed with FGFs, and its
      expression is both induced after activation and downregulated after inhibition of
      FGF signalling. In gain- and loss-of function experiments, FLRT3 and FLRT2
      phenocopy FGF signalling in Xenopus laevis. XFLRT3 signalling results in
      phosphorylation of ERK and is blocked by MAPK phosphatase 1, but not by
      expression of a dominant-negative phosphatidyl inositol 3-OH kinase (PI(3)K)
      mutant. XFLRT3 interacts with FGF receptors (FGFRs) in co-immunoprecipitation
      experiments in vitro and in bioluminescence resonance energy transfer assays in
      vivo. The results indicate that XFLRT3 is a transmembrane modulator of FGF-MAP
      kinase signalling in vertebrates.

PMID- 14688795
TI  - SOS response promotes horizontal dissemination of antibiotic resistance genes.
AB  - Mobile genetic elements have a crucial role in spreading antibiotic resistance
      genes among bacterial populations. Environmental and genetic factors that
      regulate conjugative transfer of antibiotic resistance genes in bacterial
      populations are largely unknown. Integrating conjugative elements (ICEs) are a
      diverse group of mobile elements that are transferred by means of cell-cell
      contact and integrate into the chromosome of the new host. SXT is a approximately
      100-kilobase ICE derived from Vibrio cholerae that encodes genes that confer
      resistance to chloramphenicol, sulphamethoxazole, trimethoprim and streptomycin.
      SXT-related elements were not detected in V. cholerae before 1993 but are now
      present in almost all clinical V. cholerae isolates from Asia. ICEs related to
      SXT are also present in several other bacterial species and encode a variety of
      antibiotic and heavy metal resistance genes. Here we show that SetR, an SXT
      encoded repressor, represses the expression of activators of SXT transfer. The
      'SOS response' to DNA damage alleviates this repression, increasing the
      expression of genes necessary for SXT transfer and hence the frequency of
      transfer. SOS is induced by a variety of environmental factors and antibiotics,
      for example ciprofloxacin, and we show that ciprofloxacin induces SXT transfer as
      well. Thus, we present a mechanism by which therapeutic agents can promote the
      spread of antibiotic resistance genes.

PMID- 14688796
TI  - Spinal cord involvement in the nonhuman primate model of Lyme disease.
AB  - Lyme borreliosis is a multisystemic disease caused by infection with various
      genospecies of the spirochete Borrelia burgdorferi. The organs most often
      affected are the skin, joints, the heart, and the central and peripheral nervous
      systems. Multiple neurological complications can occur, including aseptic
      meningitis, encephalopathy, facial nerve palsy, radiculitis, myelitis, and
      peripheral neuropathy. To investigate spinal cord involvement in the nonhuman
      primate (NHP) model of Lyme borreliosis, we inoculated 25 adult Macaca mulatta
      with B. burgdorferi sensu strictu strains N40 by needle (N=9) or by tick (N=4) or
      297 by needle (N=2), or with B. burgdorferi genospecies garinii strains Pbi
      (N=4), 793 (N=2), or Pli (N=4) by needle. Immunosuppression either transiently
      (TISP) or permanently (IS) was used to facilitate establishment of infection.
      Tissues and fluids were collected at necropsy 7-24 weeks later. Hematoxylin and
      eosin staining was used to study inflammation, and immunohistochemistry and
      digital image analysis to measure inflammation and localize spirochetes. The
      spirochetal load and C1q expression were measured by TaqMan RT-PCR. The results
      showed meningoradiculitis developed in only one of the 25 NHP's examined, TISP
      NHP 321 inoculated with B. garinii strain Pbi. Inflammation was localized to
      nerve roots, dorsal root ganglia, and leptomeninges but rarely to the spinal cord
      parenchyma itself. T cells and plasma cells were the predominant inflammatory
      cells. Significantly increased amounts of IgG, IgM, and C1q were found in
      inflamed spinal cord. Taqman RT-PCR found spirochetes in the spinal cord only in
      IS-NHP's, mostly in nerve roots and ganglia rather than in the cord parenchyma.
      C1q mRNA expression was significantly increased in inflamed spinal cord. This is
      the first comprehensive study of spinal cord involvement in Lyme borreliosis.

PMID- 14688797
TI  - Indications for peripheral light-chain revision and somatic hypermutation without
      a functional B-cell receptor in precursors of a composite diffuse large B-cell
      and Hodgkin's lymphoma.
AB  - Composite lymphomas are rare combinations of Hodgkin's lymphoma (HL) and non
      Hodgkin's lymphoma in the same patient, where clonal relatedness has been
      observed in most of the few cases analyzed. Here, we report a composite classical
      HL and diffuse large B-cell lymphoma (DLBCL) with interesting molecular features.
      Micromanipulation of single cells and analysis of V gene rearrangements revealed
      clonal relatedness with shared and distinct mutations, indicative of derivation
      from a common germinal center (GC) B-cell precursor and also of further
      development of both lymphomas in a GC. In the DLBCL, a very high mutation load,
      including inactivating mutations, and two copies of the same clonal rearrangement
      with different mutations in single cells were observed. Intriguingly, in the
      DLBCL precursor somatic hypermutation activity continued after acquisition of
      destructive V gene mutations, a feature previously found only in Epstein-Barr
      virus (EBV) infected B-cell expansions. Furthermore, we found evidence of light
      chain receptor revision in the lymphoma precursor during a GC reaction. Re
      expression of the V(D)J recombination machinery may enhance genomic instability
      in GC B cells and contribute to lymphomagenesis.

PMID- 14688798
TI  - Low O2 and high CO2 in LLC-PK1 cells culture mimics renal ischemia-induced
      apoptosis.
AB  - Ischemia, absence or loss of blood flow in organs always presents as a dual
      phenomenon: tissue oxygen deficit and CO(2) excess (hypercapnia). Commonly
      hypoxic cell culture models kept CO(2) at normal nonischemic values. We report a
      study of apoptosis in an in vitro model of renal hypoxia that mimics in vivo
      tissue gas atmosphere composition determined during experimental ischemia in rat
      kidney (low O(2) plus high CO(2)). Renal tubular LLC-PK1 cell were transiently
      exposed to hypoxia, to hypercapnia or to both conditions (simulated ischemia).
      Exposure to simulated ischemic atmosphere, but not to low O(2) or high CO(2)
      alone, induced cell apoptosis in vitro. This suggests that ischemia-induced
      apoptosis in vivo would be dependent on the natural, joint action of hypoxia and
      hypercapnia. This should be taken into account in cell culture studies that would
      like to mimic in vivo ischemic conditions.

PMID- 14688799
TI  - Hematopoietic progenitor cells as possible origins of epithelial thymoma in a
      human T lymphocyte virus type I pX gene transgenic rat model.
AB  - We earlier reported that Fischer 344/jcl strain (F344) rats carrying a unique pX
      gene of human T lymphocyte virus type I (HTLV-I) under control of a rat
      lymphocyte-specific protein tyrosine kinase (p56lck) type I promoter (lck-pX
      rats) spontaneously developed epithelial thymomas from the thymic medulla. To
      investigate the role of bone marrow cells carrying the HTLV-I pX gene in
      development of thymomas, the bone marrow of normal F344 rats after lethal
      irradiation was reconstituted by bone marrow mononuclear cells (BMMC) of lck-pX
      rats. Epithelial thymomas similar to the original thymoma of lck-pX rats
      frequently developed in the nontransgenic recipients within 5 months after the
      BMMC transplantation. The thymomas expressed the pX gene, thereby indicating the
      thymoma cells to be of donor BMMC origin. Since the thymoma also developed in
      nontransgenic recipients reconstituted by BMMC depleted of adherent cells, it is
      suggested that nonadherent BMMC of donor lck-pX rats may migrate to and lodge in
      the thymus of recipient nontransgenic rats then transform into thymoma cells with
      epithelial characteristics. The thymoma cells were shown to bind to Ulex
      europaeus Agglutinin-1 (UEA-1) lectin, which binds epithelial cells in the thymic
      medulla. It was also shown that the nonadherent BMMC fraction used for bone
      marrow reconstitution contained a number of UEA-1-positive cells. Taken together,
      UEA-1 positive BMMC may be progenitor cells of the epithelial thymoma. The
      epithelial thymoma in lck-pX rats sheds light on epithelial cell development in
      thymic medulla and for oncogenesis of epithelial thymoma in humans.

PMID- 14688800
TI  - Portal tract fibrogenesis in the liver.
AB  - The portal area is the 'main entrance' and one of the two main exits of the liver
      lobule. Through the main entrance portal and arterial blood reach the liver
      sinusoids. Through the exit the bile flows towards the duodenum. The three main
      structures, portal vein and artery with their own wall (and vascular smooth
      muscle cells) and bile duct with its basal membrane, are surrounded by loose
      myofibroblasts and by the first layer of hepatocytes and non-parenchymal cells.
      Chronic diseases of the liver can lead to development of liver cirrhosis,
      characterized by formation of fibrotic septa which can be portal-portal in the
      case of the chronic biliary damage or portal-central in the case of the chronic
      viral hepatitis. Central-central septa can also be observed under other
      pathological conditions. When damaging noxae are introduced to the liver,
      inflammatory cells are first recruited to the portal field, the first layer of
      hepatocytes may be destroyed (enlargement of the portal field) and portal
      (myo)fibroblasts become activated. A similar reaction may take place when the
      target of inflammation is the bile duct with consecutive reduction of the bile
      flow, activation of the portal (myo)fibroblasts, proliferation of bile ducts and
      destruction of the hepatocytes around the portal field. Increased matrix
      deposition may be the consequence. During the past years several publications
      dealt with the pathomechanisms of portal fibrogenesis as well as with its
      resolution. One of the most intriguing observations was that it is not hepatic
      stellate cells of the hepatic sinusoid, but portal (myo)fibroblasts which rapidly
      acquire the phenotype of 'activated' (myo)fibroblasts in the early stages of
      cholestatic fibrosis. These may also become the main mesenchymal cells of the
      porto-portal or porto-central fibrotic septa. This article reviews the
      similarities as well as differences between the mesenchymal cells of the portal
      tract and of the fibrotic septa vs 'activated' stellate cells of the hepatic
      sinusoids, and discusses the debate over their relative contributions to liver
      fibrogenesis.

PMID- 14688801
TI  - Toll-like receptor 4 is expressed with enteroviral replication in myocardium from
      patients with dilated cardiomyopathy.
AB  - Expressions of innate immune response proteins, most notably proinflammatory
      cytokines, against enteroviral (EV) infection have been documented in the heart
      of human dilated cardiomyopathy (DCM). Toll-like receptor 4 (TLR4) activates
      signaling pathways leading to the expression of proinflammatory cytokines
      implicated the etiology of DCM. We sought to determine whether EV replication
      activates TLR4-dependent immune response in myocardium obtained from patients
      with DCM. Endomyocardial biopsy tissues were obtained from 56 patients with DCM
      and 10 controls. Levels of plus- and minus-strand EV RNA and TLR4 mRNA were
      measured by real-time RT-PCR. Immunohistochemical analysis was performed to
      identify the cellular source of EV capsid protein VP1 and TLR4. Both plus- and
      minus-strand EV RNA were detected in 19 DCM patients (34%). Neither strand of EV
      RNA was detected in controls. TLR4 mRNA levels were higher in DCM patients than
      in controls (P<0.001). A positive correlation was found between TLR4 levels and
      each strand type of EV RNA in EV RNA-positive patients (plus-strand vs TLR4:
      r=0.69, P<0.001; minus-strand vs TLR4: r=0.65, P=0.002). VP1/TLR4 double staining
      showed extensive colocalization of VP1 and TLR4 proteins in cytoplasm of cardiac
      myocytes in myocardium obtained from DCM patients. EV RNA-positive patients
      showed lower systolic function and larger ventricular volume compared with EV RNA
      negative patients left ventricular ejection fraction (LVEF): P=0.002; left
      ventricular end-systolic diameter (LVESD): P=0.004). The DCM subgroup with high
      TLR4 levels showed lower LVEF and larger LVESD than the subgroup with TLR4 levels
      (both P<0.001). This study suggests that myocardial expression of TLR4 associates
      with EV replication in human DCM. EV RNA and TLR4 mRNA levels may correlate with
      LV dysfunction in DCM. The expression of TLR4 against EV replication may be
      involved in the pathogenesis of DCM.

PMID- 14688802
TI  - Pre-eclampsia is associated with the failure of melanoma cell adhesion molecule
      (MCAM/CD146) expression by intermediate trophoblast.
AB  - The purpose of this study was to determine whether the expression of melanoma
      cell adhesion molecule (MCAM/CD146), like most other endothelial adhesion
      molecules, is reduced in the pregnancy disorder pre-eclampsia, and whether it is
      associated with the invasiveness of trophoblast. We used immunohistochemical
      approaches and analyzed 42 placentas from control and pre-eclamptic patients
      using an anti-CD146 monoclonal antibody. Our data show that in normal placentas,
      CD146 staining was specifically detected in intermediate trophoblasts that are
      most invasive and migratory, but not detected in noninvasive cytotrophoblasts or
      syncytiotrophoblasts. However in pre-eclampsia, CD146 was no longer present in
      the intermediate trophoblasts, although it was detectable in the blood vessels.
      At the same time, we tested CD31/PECAM-1, another endothelial adhesion molecule,
      and found its negative staining for all kinds of trophoblasts in both normal and
      pre-eclamptic placentas. The different staining patterns of CD146 in the normal
      and pre-eclamptic placentas provide the first evidence that in pre-eclampsia,
      intermediate trophoblasts fail to express CD146, implicating that CD146 plays an
      important role in trophoblast invasion.

PMID- 14688803
TI  - Rapid tumor death model for evaluation of new therapeutic agents for adult T-cell
      leukemia.
AB  - Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasm. The health
      of ATL patients rapidly deteriorates resulting in death; however, the induction
      of death in a small animal model due to tumor has not yet been reported. SCID
      mice, 5 weeks old, younger than those previously used, which were inoculated with
      ATL cells, eliminated NK cell activity and showed rapid tumor formation resulting
      in death. Age is the crucial factor influencing tumor formation and death in the
      SCID mice model for cancer.

PMID- 14688804
TI  - Relation between insulin and aortic stiffness: a population-based study.
AB  - Recent studies have suggested that a high pulse wave velocity (PWV), a measure of
      aortic stiffness, may be a stronger risk factor for cardiovascular disease (CVD)
      than a high blood pressure (BP). The relation between insulin, believed to play
      an important role in the development and clinical course of high BP, and PWV is
      not yet clear. Therefore, we decided to examine the relationship between insulin
      and PWV in a large population-based study. The study population consisted of a
      random sample of 1213 women and 1207 men (age range, 41-72 years) without a
      history of myocardial infarction or stroke. Fasting insulin was determined
      together with conventional risk factors for CVD. PWV was recorded
      transcutaneously by a mechanical electrical principle with one transducer
      positioned over the left common carotid artery, and another over the left femoral
      artery. In univariate analysis, insulin was highly significantly related to PWV
      (standardized regression coefficient: 0.0669+/-0.0051; P<0.001). In multivariate
      analysis, controlling for all well-established predictors of PWV, such as age,
      systolic BP or mean BP and pulse pressure, sex, and heart rate, as well as
      controlling for conventional risk factors for CVD and use of BP-lowering drugs,
      the level of insulin remained a significant predictor of PWV (standardized
      regression coefficient: 0.0122+/-0.0048; P=0.012). In conclusion, the present
      study found that a higher insulin level was related to a higher PWV. This
      indicates that hyperinsulinaemia may affect BP and risk of CVD by increasing
      aortic stiffness.

PMID- 14688805
TI  - Specific alcoholic beverage and blood pressure in a middle-aged Japanese
      population: the High-risk and Population Strategy for Occupational Health
      Promotion (HIPOP-OHP) Study.
AB  - The purpose of this study was to clarify the effects of popular Japanese
      alcoholic beverages on blood pressure. We performed a cross-sectional study on
      4335 Japanese male workers using baseline data from an intervention study. We
      defined six groups according to the type of alcoholic beverage that provided two
      thirds of the subject's total alcohol consumption: beer, sake (rice wine), shochu
      (traditional Japanese spirits), whiskey, wine and others. The partial regression
      coefficients of daily alcohol intake (1 drink=11.5 g of ethanol) to systolic
      blood pressure (SBP) and diastolic blood pressure (DBP) were 0.87(P<0.001,
      standard error (s.e.)=0.09) and 0.77(P<0.001, s.e.=0.06), respectively. A
      comparison among the types of alcoholic beverages mainly consumed revealed
      significant differences in SBP and DBP. Both SBP and DBP were highest in the
      shochu group. However, an analysis of covariance adjusting for total alcohol
      consumption resulted in the disappearance of these differences. Although after
      adjustment for total alcohol consumption, the shochu group exhibited a
      significant positive association with 'high-normal blood pressure or greater'
      (odds ratio 1.43, 95% confidence interval 1.06-1.95) compared with the beer
      group, this significant relation disappeared after adjusting for the body mass
      index (BMI), urinary sodium and potassium excretion. The pressor effect, per se,
      of popular Japanese alcoholic beverages on blood pressure may not be different
      among the types of alcoholic beverages after adjusting for other lifestyle
      factors.

PMID- 14688806
TI  - Diagnostic value of carotid intima-media thickness and plaque score for
      predicting target organ damage in patients with essential hypertension.
AB  - Carotid intima-media thickness (IMT) assessed by ultrasonography is regarded as
      an early predictor of general arteriosclerosis in patients with essential
      hypertension. However, the methods of measuring IMT have not been globally
      standardized, and it remains unclear whether conventional measurement of IMT
      represents the prevalence of hypertensive target organ damage. In this study, we
      verified the association between several commonly used carotid ultrasonographical
      parameters and the severity of hypertensive target organ damage (retinal
      arteriosclerosis, microalbuminuria, left ventricular hypertrophy (LVH)). Carotid
      ultrasonography, echocardiography, urinalysis, and funduscopy were performed in
      184 patients (64 +/- 12 years, 96 males and 88 females) with various stages of
      essential hypertension. Carotid arteriosclerosis was assessed using four
      methodologically different methods: conventional-IMT, maximum-IMT (Max-IMT), Mean
      IMT, and Plaque Score (the sum of all plaque thicknesses). Age and all carotid
      ultrasonographical parameters were significantly associated with albuminuria,
      retinal arteriosclerosis, and left ventricular mass index. High-sensitivity CRP
      was significantly correlated with retinopathy and LVH. Carotid parameters in
      patients with histories of cardiovascular events were significantly greater in
      those without events. Among all carotid parameters, Max-IMT showed the highest
      correlation coefficient of the severity of target organ damage, and showed
      significant association with CRP. Stepwise regression analysis revealed that Max
      IMT was the independent factor for predicting target organ damage. Max-IMT is
      suggested to be the most reliable and simplest parameter for predicting
      hypertensive target organ damage including microangiopathy in patients with
      essential hypertension.

PMID- 14688807
TI  - Polymorphisms of the angiotensinogen gene and the outcome of microalbuminuria in
      essential hypertension: a 3-year follow-up study.
AB  - BACKGROUND: The objective of this study was to analyse the relationship of
      polymorphisms of the angiotensinogen (AGT) gene with the changes in
      microalbuminuria during 3 years of antihypertensive treatment in a group of young
      adults with essential hypertension. METHODS: Essential hypertensives, less than
      50 years old, never previously treated with antihypertensive drugs and in the
      absence of diabetes mellitus were included. After the initial evaluation,
      patients were treated using only nonpharmacological measures (n=23), only beta
      blockers (n=26), only angiotensin-converting enzyme inhibitors (ACEi) (n=57) or a
      combination of treatments (n=25). The office blood pressure, biochemical profile
      and urinary albumin excretion (UAE) were measured at the beginning and then
      yearly. The polymorphism A-6G of the AGT gene located in the promoter region was
      analysed. RESULTS: In total, 131 patients, 35 (27%) microalbuminurics, were
      included. Although no significant differences in systolic blood pressure (SBP),
      diastolic blood pressure (DBP), fasting glucose and UAE were observed among
      genotypes at the initial examination, during the 3 years of antihypertensive
      treatment the slope values for the DBP, fasting glucose and UAE differed
      significantly despite no differences in the distribution of treatments being
      present. The subjects carrying the AA-6 genotype had the largest DBP decrease,
      but the lowest UAE reduction and the highest slope of glucose. Out of 35
      initially microalbuminuric patients, 24 became normoalbuminuric and the lowest
      reduction rates were observed in subjects who carried the allele A-6. No
      interaction between the type of treatment and genotype was observed on the
      changes in UAE, BP or glucose values. In the subset of 57 patients treated with
      ACEi, the changes in UAE, BP and glucose had the same trend as was observed in
      the total population. CONCLUSIONS: Subjects carrying the AA genotype of the A-6G
      AGT gene polymorphism are resistant to a reduction of microalbuminuria. Whether
      this can be attributed to a predisposition to glucose metabolic disturbance or
      not needs to be confirmed in further studies.

PMID- 14688808
TI  - Electrocardiographic assessment of left ventricular hypertrophy with time-voltage
      QRS and QRST-wave areas.
AB  - The sum of time-voltage QRS areas in the 12-lead electrocardiogram (ECG) has
      outperformed other 12-lead ECG indices for detection of left ventricular
      hypertrophy (LVH). We assessed indices of time-voltage QRS and T-wave (QRST)
      areas from body surface potential mapping (BSPM) for detection of and
      quantitation of the degree of LVH. We studied 42 patients with echocardiographic
      LVH (LVH group) and 11 healthy controls (controls). QRST area sums were
      calculated from 123-lead BSPM and from the 12-lead ECG for comparison. Leadwise
      discriminant indices and correlation coefficients were used to identify optimal
      recording locations for QRST area-based LVH assessment. BSPM QRS area sum was
      greater in the LVH group than in controls (3752 +/- 1259 vs 2278 +/- 627 microV
      s, respectively; P<0.001) and at 91% specificity showed 74% sensitivity for LVH
      detection. The 12-lead QRS area sum performed similarly. Taking T-wave areas into
      account did not improve the results. QRS area sum from two most informative leads
      (located in the upper and lower right precordium) also separated the LVH group
      from controls (61.1 +/- 23.5 vs 27.8 +/- 6.5 microV s, respectively; P<0.00001).
      This 2-lead QRS area sum showed 90% sensitivity with 100% specificity for LVH
      detection and maintained high correlation to indexed left ventricular mass
      (r=0.732; P<0.001). In conclusion, the BSPM QRS area sum compared to 12-lead QRS
      area sum does not substantially improve LVH assessment. The 2-lead QRS area sum
      may improve ECG QRS area-based LVH assessment.

PMID- 14688809
TI  - Longevity-associated mitochondrial DNA 5178 A/C polymorphism and blood pressure
      in the Japanese population.
AB  - It has been reported that the mitochondrial DNA 5178 adenine/cytosine (mt5178
      A/C) polymorphism, also called NADH dehydrogenase subunit 2-237
      methionine/leucine (ND2-237 Met/Leu) polymorphism, may be associated with
      longevity in Japanese individuals, and that the mt5178A genotype may have an
      antiatherogenic influence. To determine whether mt5178 A/C polymorphism
      influences blood pressure, we genotyped 412 healthy Japanese individuals and
      performed a cross-sectional study investigating the relationship between genotype
      and blood pressure. In women with mt5178A, the mean diastolic blood pressure was
      higher than in those with mt5178C by 3.2 mmHg (P=0.040). In men, no statistically
      significant difference in systolic or diastolic blood pressure was observed
      between mt5178 A/C genotypes. However, a significant correlation between mt5178
      A/C genotypes and the effects of habitual drinking on blood pressure was found.
      After adjustment for several factors, in men carrying mt5178C, both systolic and
      diastolic blood pressure were significantly higher in daily drinkers than in
      occasional (P=0.002 and 0.002, respectively) as well as nondrinkers (P<0.001 and
      0.001, respectively), whereas in men carrying mt5178A, no significant differences
      in blood pressure were detected, irrespective of alcohol consumption. These
      results suggest that mt5178 A/C (=ND2-237 Met/Leu) polymorphism may influence
      both diastolic blood pressure in Japanese women and the blood-pressure-increasing
      effect of drinking in Japanese men.

PMID- 14688810
TI  - Coexistence of different phenotypes in a family with glucocorticoid-remediable
      aldosteronism.
AB  - In glucocorticoid-remediable aldosteronism (GRA), there is a large interfamily
      variation of phenotype. We report three subjects with GRA in a single family
      (parents, two brothers and two sisters), of whom only one (proband) displayed
      classical features of the mineralocorticoid excess. The proband was a man found
      to be hypertensive and hypokalaemic at the age of 24 years. Plasma renin activity
      was suppressed and plasma aldosterone was repeatedly elevated. Blood pressure and
      aldosterone levels normalized within 5 days of dexamethasone therapy. The
      presence of a chimaeric CYP11B1/CYP11B2 gene was demonstrated by long-PCR and
      Southern blotting (crossover site at the end of intron 3) in the proband, in the
      younger sister (sibling 1) and in the father. In these patients, sequencing of
      the chimaeric portion of CYP11B1 did not reveal any mutation, while sequencing of
      the chimaeric portion of CYP11B2 showed a V386A polymorphism in exon 7, known to
      cause only a minimal impairment of enzymatic activity. Sibling 1 was
      normotensive, normokalaemic and had normal PRA and aldosterone. The father had
      normal blood pressure and potassium, low-normal PRA and normal aldosterone. All
      three subjects had elevated levels of urinary 18-hydroxycortisol and 18
      oxocortisol. Baseline 11-deoxycorticosterone (DOC), corticosterone (B) and
      aldosterone were high in the proband and normal in the father and sibling 1; 11
      deoxycortisol (S) and cortisol (F) were normal. ACTH induced a normal increase of
      B, DOC, S and F, and an excessive aldosterone increase in all three patients.
      Abnormalities in the chimaeric portions of CYB11B1 or CYP11B2 genes did not
      account for the phenotypic disparity of the different members in a single GRA
      family. Altered regulation of the chimaeric gene may be responsible for
      differences in its activity.

PMID- 14688811
TI  - Freehand three-dimensional echocardiographic evaluation of the effect of
      telmisartan compared with hydrochlorothiazide on left ventricular mass in
      hypertensive patients with mild-to-moderate hypertension: a multicentre study.
AB  - Antihypertensive efficacy, effects on left ventricular mass index (LVMI) and
      tolerability of telmisartan, an angiotensin II receptor blocker, were compared
      with those of hydrochlorothiazide (HCTZ). Adult patients with mild-to-moderate
      hypertension and an optimal acoustic window by two-dimensional echocardiography
      were randomised at baseline to 12 months' double-blind, once-daily treatment with
      telmisartan 80 mg or HCTZ 25 mg. Two-dimensional echocardiography and freehand
      precordial three-dimensional echocardiography and 24-h ambulatory blood pressure
      monitoring were performed at baseline and after treatment. Of the 41 telmisartan
      group patients and 28 HCTZ group patients, 40 and 25, respectively, completed the
      study. Following treatment, 24-h mean SBP (telmisartan 157 +/- 11 vs 133 +/- 7
      mmHg, P<0.001; HCTZ 154 +/- 10 vs 144 +/- 11 mmHg, P<0.003) and DBP (telmisartan
      96 +/- 6 vs 83 +/- 5 mmHg, P<0.001; HCTZ 95 +/- 7 vs 87 +/- 8 mmHg, P<0.003) were
      significantly reduced. Telmisartan produced significantly greater 24-h mean SBP
      and DBP reductions than HCTZ (P<0.001). LVMI was significantly reduced by
      telmisartan (141 +/- 16 vs 125 +/- 19 g/m2, P<0.001), but not by HCTZ (139 +/- 20
      vs 135 +/- 22 g/m(2)). Incidences of adverse events in both the treatment groups
      were low; two cases of hypokalaemia occurred with HCTZ. In conclusion,
      telmisartan 80 mg was well tolerated and significantly reduced SBP, DBP and LVMI
      after 12 months' treatment compared with HCTZ.

PMID- 14688812
TI  - Socioeconomic inequality in blood pressure and its determinants: cross-sectional
      data from Trinidad and Tobago.
AB  - We evaluated income- and education-related inequalities in blood pressure,
      hypertension and hypertension treatment in the general population of Trinidad and
      Tobago. The design included survey of 300 households in north central Trinidad,
      including 631 adults in 2001. Measurements of blood pressure, weight, height,
      waist and hip circumferences, and educational attainment, household income and
      alcohol intake by questionnaire. The slope index of inequality (SII) was used to
      estimate the difference in blood pressure between those with highest, as compared
      to lowest, socioeconomic status. Complete measurements and questionnaires were
      obtained for 461 (73%) including 202 men and 259 women. In women, after adjusting
      for age and ethnicity, the SII for systolic blood pressure by income was -12.6,
      95% confidence interval -22.6 to -2.6 mmHg (P=0.013); and -10.8 (-21.4 to -0.2)
      mmHg (P=0.045) by educational attainment. After additionally adjusting for body
      mass index, waist-hip circumference ratio and self-reported diabetes, the SII for
      income was -7.3 (-16.5 to 1.9) mmHg (P=0.120) and for educational attainment was 
      3.0 (-13.0 to 6.9) mmHg (P=0.551). In men, after adjusting for age and ethnicity,
      the SII for systolic blood pressure by income was -4.3 (-15.4 to 6.8) mmHg
      (P=0.447) and for education -8.1 (-19.0 to 2.8) (P=0.145). There is a negative
      association of systolic blood pressure with increasing income or education in
      women. This is associated with body mass index, abdominal obesity and diabetes.
      There is no consistent association between education or income and blood pressure
      in men.

PMID- 14688813
TI  - Endothelial dysfunction in patients with white coat hypertension.

PMID- 14688814
TI  - Prognostic importance of the platelet count 100 days post allogeneic bone marrow
      transplant.
AB  - We assessed the prognostic importance of the platelet count 100 days post
      transplant of 107 consecutive patients receiving ablative allogeneic bone marrow
      transplant (BMT) between 7/96 and 12/00 who survived at least 100 days. Diagnoses
      included AML (n=36), chronic myelogenous leukemia (n=27), NHL (n=14), ALL (n=16),
      MDS (n=9), aplastic anemia (n=3), and one Hodgkin's disease and myelofibrosis
      each. In total, 64% were in remission or in chronic phase or had aplastic anemia
      (good risk), and 36% had active disease at the time of transplant (bad risk). In
      all, 70% were matched sibling transplants and 30% were matched unrelated donor
      transplants. The mean follow-up for the patients remaining alive is 48 months.
      Survival was powerfully influenced by the 100-day platelet count: 4-year survival
      was 19% for patients with a platelet count <30 x 10(9)/l; 41% for patients with a
      platelet count of 30-50; and 72% for those with a platelet count >50 (P<0.001;
      log-rank test). In a multivariable analysis, the most powerful risk factors for
      mortality after allogeneic BMT were low 100-day platelet count (P<0.001) and bad
      risk disease (P=0.009). We conclude that the platelet count 100 days post
      transplant is a powerful predictor of overall survival.

PMID- 14688815
TI  - Enterovirus infections following T-cell depleted allogeneic transplants in
      adults.
AB  - Anecdotally, enteroviruses have been reported to cause serious complications post
      BMT, but the exact impact of these viruses in the post transplant period has not
      been reported. We prospectively evaluated stool, urine and throat samples for
      enteroviruses by viral culture together with relevant body fluids by RT-PCR in 64
      allograft recipients receiving grafts T-cell depleted by Campath-1H, following
      both conventional and reduced-intensity conditioning. Seven patients (10.4%)
      developed nine episodes of enterovirus infections at a median of 146 days post
      transplant. Four episodes were associated with symptomatic illnesses, which could
      be attributable to enteroviruses. There was no mortality directly related to
      enteroviruses. There was no correlation between dose and mode of Campath-1H use,
      lymphocyte recovery, IgG and IgA levels and enterovirus isolation. Although
      enteroviruses tended to be more frequent in TBI-based conventional conditioning
      recipients, the only significant risk factor for enterovirus infection was
      unrelated donor graft. The low incidence of the severe enterovirus infections
      could have been related to a low lymphocyte count in this cohort in the absence
      of GVHD, particularly CD4+ count, which has been implicated in tissue damage in
      experimental animals. Further studies are needed to define its impact in
      different allograft settings.

PMID- 14688816
TI  - The role of allogeneic bone marrow transplantation in adult patients below the
      age of 55 years with acute lymphoblastic leukemia in first complete remission: a
      donor vs no donor comparison.
AB  - The role of allogeneic bone marrow transplantation (alloBMT) in adults with acute
      lymphoblastic leukemia (ALL) in first complete remission (CR1) remains
      controversial. At our institution, the policy is to offer alloBMT to ALL patients
      in CR1 up to the age of 55 years if a related donor is available. In addition,
      unrelated donor transplants are offered to patients with Philadelphia (Ph+) ALL.
      We report the results on 92 patients with ALL treated according to this policy
      from September 1992 to October 2001. Of the 87 patients achieving CR1, the
      comparison of patients with (n=48) or without donors (n=39) was done using an
      intention-to-treat approach. Of the 48 patients with donors (39 related and nine
      unrelated), 35 (73%) received alloBMT in CR1. No significant difference in 3-year
      event-free survival (EFS) (40 vs 39%, P=0.74) or overall survival (OS) (46 vs
      58%, P=0.41) was seen in 'donor' vs 'no-donor' groups. For Ph+ patients, 3-year
      EFS and OS in 'donor' group were 46 and 57%, respectively, none of the patients
      in 'no-donor' group survived beyond 3 years. With our treatment strategy, 3-year
      OS of Ph+ patients was equivalent to Ph-negative (Ph-) patients (51 vs 52%,
      P=0.77). In conclusion, our data show that the policy of performing alloBMT if a
      sibling donor is available has not resulted in better outcome in Ph- patients.

PMID- 14688817
TI  - Donor and liability insurance of donor registries, donor centers, and collection
      centers--recommendations.
AB  - The article presents views and recommendations of the World Marrow Donor
      Association regarding the need for donor and liability insurance for
      hematopoietic stem cell donor registries, and donor and collection centers.

PMID- 14688818
TI  - Umbilical cord blood transplant in hepatitis C-associated severe aplastic anemia.

PMID- 14688819
TI  - Pulmonary function after autologous bone marrow transplantation in children: a
      long-term prospective study.
AB  - We performed serial pulmonary function tests (PFTs) consisting of spirometry and
      diffusing capacity in 26 children after BMT. The median follow-up was 10 years.
      The influence of total body irradiation (TBI) on long-term pulmonary function was
      of particular interest. In the 20 children who had received TBI, after an initial
      decrease the PFTs showed recovery, but the mean lung volumes were still
      significantly decreased 5 years after BMT at 10% below baseline. The proportions
      of children with restrictive impairment 5 and 10 years after BMT were 20 and 21%,
      respectively. Only one child was diagnosed with obstructive impairment. The
      proportions of children with isolated diffusing impairment at 5 and 10 years were
      7/20 (35%) and 7/13 (54%), respectively. Six children had received chemotherapy
      only and showed isolated diffusing impairment as the only long-term sequela in
      4/5 and 1/3 at 5 and 10 years. Our main finding was that there was little change
      in PFTs 1-10 years after BMT. TBI was associated with persistently decreased lung
      volumes in a proportion of patients, whereas chemotherapy also might have been of
      importance for the development of impaired gas exchange.

PMID- 14688820
TI  - Evaluation of histogenesis of B-lymphocytes in pediatric EBV-related post
      transplant lymphoproliferative disorders.
AB  - Post-transplant lymphoproliferative disorders (PTLD) are
      morphologically/clinically heterogeneous. The main goal of this study was to
      define the histogenesis of PTLD (B-cell phenotype, EBV-related) in seven
      pediatric patients after allogeneic T-cell-depleted bone marrow transplantation.
      Immunohistochemical stains using histogenetic markers, including Bcl-6 (expressed
      by germinal center (GC) B cells), MUM1/IFR4 (late GC and post GC B cells), and
      CD138 (post GC B cells), were performed on paraffin-embedded tissue. By
      morphology, four cases were classified as polymorphic PTLD and three as
      monomorphic PTLD, according to the WHO classification. By the expression pattern
      of histogenetic markers, five cases (two polymorphic, three monomorphic PTLD)
      were of late GC/early post GC B-cell origin expressing only MUM1/IRF4. The
      remaining two cases (one monomorphic, one polymorphic PTLD) were of post GC B
      cell origin expressing MUM1/IRF4 and CD138, but not Bcl-6. Our study indicates
      that histogenesis of PTLD may be defined by histogenetic markers using
      immunohistochemistry. The results suggest that most pediatric PTLD are of late
      GC/early post GC B-cell origin, and a minor group is of post GC B-cell origin.
      The histogenesis of PTLD appears independent of morphologic appearance. Further
      studies are warranted to confirm our observation and to evaluate the clinical
      significance of histogenetic pattern of PTLD.

PMID- 14688821
TI  - The effect of ovarian steroid deficiency on regeneration of oviductal mucosa
      following reconstructive surgery.
AB  - In patients with distal tubal occlusion a microsurgical oviductal reconstruction
      is, apart from the in vitro fertilization, the only treatment option.
      Unfortunately, the results of reconstructive surgery are often unsatisfactory.
      The effects of sex steroids on the regeneration process after reconstructive
      surgery have not been well investigated. This study was aimed to evaluate the
      effect of decreased concentrations of ovarian sex steroids (castration) on
      regeneration of the oviduct mucosa after the reconstructive surgery of distally
      occluded oviducts. The study was performed on 32 female rabbits that underwent
      unilateral oviduct ligature and resection of fimbriae. The occlusion lasted six
      (group I) or twelve weeks (group II). After this time the animals were re
      operated, and allocated into 4 groups: castration with reconstructive surgery
      (IA, IIA), reconstructive surgery only (IB, IIB). After next six or twelve weeks
      the fallopian tubes were examined under light, scanning and transmission electron
      microscopes. An immunohistochemical reaction for Ki-67 proliferative antigen was
      also performed. Ovarian steroid levels were evaluated by radioimmunoassays. The
      castrated animals had significantly lower levels of estradiol, progesterone and
      17-hydroxyprogesterone than the control groups. Long lasting tubal occlusion
      caused pronounced histological changes of tubal mucous membrane (group II). In
      the rabbits with preserved ovaries and twelve-week long oviductal occlusion
      (group IIB), the regeneration of the distal end and restoration of fimbria were
      not complete twelve weeks after microsurgical reconstruction. In castrated
      animals with long-lasting occlusion (group IIA) the destructive changes, found in
      the mucosa of tubal ampullas of occluded oviducts before reconstruction, were
      still present and even intensified twelve weeks following reconstructive surgery.
      The castration hampered proliferation of the mucosa cells, thus no fimbriae were
      restored. Low levels of ovarian steroids were found to have adverse effect on
      fallopian tube regeneration following reconstructive surgery. The effect was
      noted even in cases with minor preoperative fallopian tube damage. Therefore, the
      treatment of concomitant endometriosis or uterine fibroids with GnRH analogues
      should not be recommended simultaneously with microsurgical tubal reconstruction.

PMID- 14688822
TI  - Changes in germ cell population in young and adult female mice from two inbred
      strains: CBA/Kw and KE.
AB  - Female mice from two inbred strains CBA/Kw and KE differ markedly in fertility.
      The gametes of females from KE strain are of poorer quality than those of CBA/Kw.
      We analyzed the number of oocytes per ovary in KE and CBA/Kw mice aged 5, 25, 90,
      180 and 360 days. The ovaries were dissected and processed according to the
      routine histological methods. In case of five-day-old females we used a modified
      distributed point counting method while in order to examine the gonads of older
      females, the nucleoli counting method was applied. In general, we observed
      gradual decrease in germ cell number throughout the whole life of females from
      both strains. The noticeable wave of oocyte loss occurs between 5th and 25th days
      of life. The mice from KE inbred strain on day 25th (1650 +/- 322 vs. 1140 +/-
      210) and 90(th) (1040 +/- 211 vs. 692 +/- 89) days have significantly (p<0.005)
      more germ cells than the females from CBA/Kw strain. In older females the
      differences were not statistically significant. Interestingly, CBA/Kw females
      were found to have more rapid loss of primordial follicles throughout their
      lives. This can explain their shortened reproductive lifespan which was observed
      earlier.

PMID- 14688823
TI  - In vitro effect of leptin on steroids' secretion by FSH- and LH-treated porcine
      small, medium and large preovulatory follicles.
AB  - The role of exogenous leptin in the follicular steroidogenesis in pigs has not
      been fully elucidated and available data are controversial. In the current study
      porcine follicles were recovered from ovaries during early, middle, and
      preovulatory stages of the follicular phase of the estrous cycle. Follicles were
      cultured in the presence of the recombinant ovine leptin (oLEP) with or without
      LH (100 ng/ml) or FSH (100 ng/ml). Medium estradiol (E(2)), testosterone (T) and
      progesterone (P(4)) concentrations were determined after 48h of culture. Leptin
      at a dose of 2 ng/ml had no effect on basal E(2) and T secretion by small and
      medium follicles but decreased E(2) secretion by large follicles. Significant
      synergistic action of FSH and leptin resulting in a 2 - 5 fold stimulation of
      E(2) secretion by small and medium follicles was observed. The aromatase
      inhibitor, CGS 16949A augmented T secretion and inhibited E(2) secretion by
      control and FSH-treated medium follicles. In FSH and leptin-treated follicles,
      the inhibitory action of CGS 16949A on E(2) secretion was observed. However,
      there was no augmentation of T secretion. In leptin-treated follicles the
      stimulatory action on P(4) secretion was observed only during the preovulatory
      stage. In these follicles, significant synergistic action of leptin with LH on
      P(4) secretion was also noted. These results indicate that there is a maturation
      dependent action of leptin on both E(2) and P(4) secretion. They also suggest a
      synergistic action of leptin and FSH on E(2) secretion by small and medium
      follicles as well as leptin and LH on P(4) secretion by large follicles in pigs.

PMID- 14688824
TI  - Intramuscular injections of male pheromone 5 alpha-androstenol change the
      secretory ovarian function in gilts during sexual maturation.
AB  - In addition to the standard olfactory pathway typical for signaling pheromones,
      the existence of a humoral pathway for the priming action of pheromones has been
      earlier postulated. In this study in vivo experiment was performed to establish
      whether intramuscular injections of boar pheromone, 5 alpha-androstenol (5 alpha
      androst-16-en-3-ol), might change the development and secretory function of the
      ovarian follicles during sexual maturation of gilts. Gilts from groups I (n=15)
      and II (n=13) received androstenol (10 microg/gilt/injection; i.m.) three times a
      week from day 192 to 234 of age. Similar, control gilts (group C; n=13) received
      saline. Additionally, the nasal cavity of animals from group II was irrigated
      with zinc sulfate solution to depress olfactory function. The reproductive organs
      and follicular fluid were collected on day 240 of age. There were no significant
      differences among groups concerning the weight of the ovary and uterus, the
      length of the uterine horns and intensity of cytochrome P450(scc) and P450(arom)
      immunoexpression. However, gilts treated with boar pheromone had a higher
      (p<0.01) total number of follicles > 3 mm in diameter and a lower index of
      atresia. In addition, androstenol-treated animals were characterized by higher
      concentrations of progesterone (the 1-3 mm and 3-6 mm follicles; p<0.01 and
      0.001, respectively) and estradiol (follicles 3-6 mm; p<0.001) than those of
      controls. The results of the present study demonstrate that intramuscular
      injections of androstenol stimulate the development and secretory function of the
      ovarian follicles in gilts during sexual maturation. They also support the
      hypothesis that androstenol, as a priming boar pheromone, may influence
      reproductive processes in female pigs acting as a chemical signal via humoral
      pathway.

PMID- 14688825
TI  - The assessment of LIF in uterine flushing--a possible new diagnostic tool in
      states of impaired fertility.
AB  - The objective of this study was to assess the LIF (leukemia inhibitory factor)
      concentration in uterine flushing and serum (ELISA) of women with proven
      fertility, infertile women and women with recurrent miscarriage. In addition,
      progesterone level was determined in serum. A decreased production of LIF in the
      uterine microenvironment was found in states of impaired fertility. With a cut
      off point of 8.23 pg/ml for LIF level in uterine flushings we have achieved 86.7%
      sensitivity and 100% specificity in detection of women with idiopathic
      infertility compared to fertile controls. No correlation between LIF in serum and
      uterine flushing was demonstrated, rendering LIF measurements in serum useless
      for diagnosis of impaired infertility. We conclude that LIF measurement in
      uterine flushing could be a useful diagnostic tool to predict unsuccessful
      implantation.

PMID- 14688826
TI  - Viral hepatitis: new data on hepatitis C infection.
AB  - Viral hepatitis (VH) is almost as old as human beings, at least as old as known
      human history. However, the natural history and the epidemiology of the disease
      has undergone changes during the centuries and even recently we have been facing
      several new aspects. The estimated global prevalence is around 3-5%, which means
      that approximately 400 million patients are infected with hepatitis B virus and
      that there are 170 million infections with hepatitis C virus. The mortality
      figures are projected to show a 2- to 3-fold increase over the next two decades
      as hepatitis C virus-infected patients develop cirrhosis, which makes this the
      leading indication for liver transplantation. These data point to the importance
      of VH being a significant public health problem worldwide. The list of
      hepatotropic viruses is well known, including hepatitis A (HAV), B (HBV), C
      (HCV), D (HDV), E (HEV), G (HGV) and F (HFV). HGV and HFV are excluded from the
      present review, mainly because they are questionable in relation to the causation
      of liver disease. Our knowledge of HAV, HBV, HDV and HEV has accumulated over the
      last decade, so the present discussion is focused on HCV, which is currently
      generating considerable concern and controversy, and is the leading cause of
      chronic liver disease worldwide. The main questions to be discussed, are: the
      characterization of the agents' viral genotypes/subtypes, the viral-cell
      interaction, the pathogenesis of VH, the extrahepatic manifestations of viral
      infection and hepatocarcinogenesis.

PMID- 14688827
TI  - HCV and HGV infection in Hodgkin's disease.
AB  - Numerous observations imply that the pathogenesis of malignant lymphomas is
      multifactorial and that viruses probably play an important etiologic role.
      Besides Epstein-Barr virus, there might be other viruses among the causes of
      Hodgkin's disease. A total of 111 randomly selected patients with Hodgkin's
      disease were included in this study, and hepatitis C and G viruses were tested
      with polymerase chain reaction. The results were compared to hepatitis C and G
      virus infection ratios assessed by polymerase chain reaction in the Hungarian
      blood bank. Hepatitis C virus was diagnosed in 10 (9%) patients, and hepatitis G
      virus in 9 (8,1%), which is a 12-fold and a 1,5-fold infection rate as compared
      to that of the Hungarian blood bank, respectively. There was no significant
      difference between hepatitis positive and negative patients concerning mean age
      at the time of diagnosis, sex, disease stage, histology type, treatment applied,
      risk factors in the history of the infection and liver enzymes. Hepatitis C virus
      positivity in patients with Hodgkin's disease differs significantly from that in
      blood donors. Based on these results and data in the literature, no definite
      statement can be made on the etiological role of viruses, but further studies are
      needed.

PMID- 14688829
TI  - Pseudohyperplastic prostatic adenocarcinoma in transurethral resections of the
      prostate.
AB  - Pseudohyperplastic prostatic adenocarcinoma is a recently described variety of
      adenocarcinoma that has been studied in core-needle biopsies and prostatectomy
      specimens. It is characterized by malignant glands that simulate benign
      hyperplastic glands with complex, medium to large-sized glands with papillary
      infoldings, luminal undulations, branching or cystic dilatations, and columnar
      cells with macronucleoli and nuclear enlargement. Our aim was to define
      frequency, tumor volume, and histologic features of pseudohyperplastic prostatic
      adenocarcinoma in transurethral resections of prostate. We studied 250 specimens
      from transurethral resections; 150 specimens were originally diagnosed as benign
      glandular hyperplasia, and 100 as conventional prostate adenocarcinomas. Of the
      150 biopsies originally diagnosed as benign glandular hyperplasia, two (1.3%) had
      areas of pseudohyperplastic carcinoma. In both cases the neoplasm was limited to
      two chips and measured 3 and 4 mm in diameter, respectively. Both patients were
      asymptomatic 2 and 4 years after diagnosis. Of the 100 biopsies with
      adenocarcinoma, areas of pseudohyperplastic carcinoma were found in three cases.
      In the first two these areas were found in two fragments, and in the other case
      they were found in three chips, and measured 3, 4, and 6 mm, respectively. The
      clinical course in these cases was unfavorable, and two patients had metastasis.
      Main histologic findings included crowded glands (5/5), papillary projections
      (5/5), nuclear enlargement (5/5) macronucleoli (4/5) cystic glandular dilatation
      (4/5) straight luminal borders (4/5), pink amorphous secretions (4/5) nuclear
      hyperchromasia (3/5) and transition to small acinar pattern of adenocarcinoma
      (3/5). In conclusion, pseudohyperplastic prostate carcinoma is rare in
      transurethral resection specimens and is found in scarce chips. Frequency of
      false negative results in biopsies originally diagnosed as benign glandular
      hyperplasia was 1.3%. In biopsies diagnosed as carcinoma, this frequency was 3%.
      These patients had an adverse clinical course, apparently due to association with
      areas of conventional adenocarcinoma.

PMID- 14688828
TI  - Significance of p53, Bcl-2, and HER-2/neu protein expression in Omani Arab
      females with breast cancer.
AB  - Racial disparity in the presentation of breast cancer and the outcome of its
      treatment is well established. However, the causes remain unexplained. The
      scarcity of reports about the prognostic significance of p53, bcl-2, and HER
      2/neu in Arab females with breast cancer has been the impetus to this study. We
      evaluated the prognostic significance of altered expression of p53, bcl-2, HER
      2/neu in Omani Arab females with non-metastatic breast cancer with correlation to
      other established prognostic factors. We have retrospectively analyzed the
      immunohistochemical expression of p53, HER-2/neu and bcl-2 in paraffin embedded
      blocks of 72 females diagnosed with invasive breast cancer between 1992 and 2002.
      The expression of the above proteins was correlated with other prognostic factors
      and univariate and multivariate analysis was carried out for all prognostic
      factors. Overexpression of p53 significantly correlated with younger age (<40),
      pre-menopausal status, poor differentiation with inverse correlation with bcl-2
      expression. Expression of bcl-2 immunopostivity significantly correlated to low
      histological grade and positive estrogen and progesterone receptor status. On
      univariate and multivariate p53 overexpression and lack of bcl-2 immunostaining
      resulted in worse survival outcome, but not Her-2/neu overexpression. Expression
      patterns of p53 and bcl-2 are independent predictors of survival in Omani Arab
      population which may help to stratify these patients into different risk groups.

PMID- 14688830
TI  - hMLH1 and hMSH2 somatic inactivation mechanisms in sporadic colorectal cancer
      patients.
AB  - Much is known about the role of germline inactivation in mismatch repair (MMR)
      genes in hereditary non-polyposis colorectal cancer (HNPCC), but the impact of
      somatic MMR gene changes on sporadic colorectal cancer remains to be elucidated.
      In hereditary cases the hMLH1 and hMSH2 genes were shown to have a great
      importance, and in order to examine the somatic inactivation mechanisms of the
      two MMR genes hMLH1 and hMSH2 we screened 37 Hungarian sporadic colorectal cancer
      patients for allelic imbalance (AI), microsatellite instability (MSI), hMLH1
      promoter hypermethylation and somatic mutations. Thirteen of the examined tumours
      (35%) were characterized by low-level MSI and none of the cases belonged to the
      high MSI group. Nine (24%) and seven (19%) cases had AI at the hMLH1 and hMSH2
      genes, respectively. Seven tumours (19%) showed dense promoter hypermethylation
      of hMLH1, but only two patients had somatic mutations, one for each MMR gene.
      According to our study on this limited set of cases the most prominent mismatch
      repair inactivation mechanism in sporadic colorectal cancer patients is the hMLH1
      promoter hypermethylation which may have a role in the carcinogenesis of sporadic
      colorectal cancer.

PMID- 14688831
TI  - Synovial sarcoma: a rare tumor of larynx.
AB  - Synovial sarcoma is a soft tissue sarcoma of unknown histogenesis and occurs
      predominantly in the lower extremities of young adults. The head and neck is a
      relative rare location. There are about 10 cases with laryngeal localization in
      the literature. We present a 24 year-old male with an endolaryngeal mass.
      Incisional biopsy and the hemilaryngectomy material revealed a biphasic synovial
      sarcoma. One year later a local recurrence occurred. Tumor excision and neck
      dissection were performed. Radiotherapy was added. Six months later lung
      metastases was discovered on thoracic CT. The patient received chemotherapy for 6
      courses. The metastases responded well to chemotherapy and the patient is now
      alive without tumor on radiological and clinical examination after 3.5 years of
      follow-up.

PMID- 14688832
TI  - Renal tumor causing haematuria and sepsis.
AB  - A 28 year old female patient developed hematuria in the 32th week of her
      pregnancy. She was given antibiotic treatment, since a urinary tract infection
      was suspected. After delivery symptoms of acute pyelonephritis, then sepsis
      developed, and conservative therapy had no effect. Ultrasound examination showed
      unusual renal destruction, so nephrectomy was performed. Surgical intervention
      revealed the presence of an advanced tumor of the kidney, while histological
      examination confirmed a Bellini duct carcinoma of the kidney.

PMID- 14688833
TI  - Giant cell fibroblastoma in a 3-year-old boy.
AB  - Giant cell fibroblastoma (GCF) is a rare soft tissue tumor most often discovered
      during the first two decades of life. We present a case of a 3-year-old boy with
      a history of a recurrent lesion in the knee, the tumor growth progressively and
      enlarged to 2.1 cm in the previous two years before diagnosis. It involved the
      subcutaneous tissue, had infiltrative borders and extended into the superficial
      dermis. The tumor was surgically excised with free margins. There was no evidence
      of local recurrence, and a metastatic workup was negative after 10 years of
      follow up. We review herein the clinicopathologic features, histogenesis,
      differential diagnosis and relationship to dermatofibrosarcoma protuberans
      (DFSP).

PMID- 14688836
TI  - [Cryptorchidism].

PMID- 14688837
TI  - [Human chorionic gonadotropin: a feasible option for treating undescended
      testes].
AB  - In order to shed light on the controversy in the literature about the efficacy of
      medical treatment of undescended testes, HCG was administered to 73 boys. They
      were seven month to twelve years old and none of them had puberty signs.
      Cryptorchidism was unilateral in 75.4%; it was bilateral in 24.6%. Children with
      retractile testes were excluded from the study. The patients received IM HCG 1500
      to 2000 IU/sqm twice a week for 5 weeks. Testicular descent was noted in 23.0% of
      the undescended testes, often in the first 2.5 weeks of therapy. All children
      were followed up for at least a year and relapse was observed in 8.3%. Clinical
      signs of testosterone action faded off shortly after the end of injections. No
      side effects were apparent by the third month after treatment. We conclude that
      the administration of HCG is worth of a trial before the surgical approach is
      contemplated in the management of the cryptorchidism.

PMID- 14688834
TI  - Pancreatic cancer - a continuing challenge in oncology.
AB  - Pancreatic cancer is still one of the major health problems because of its rising
      incidence and the modest therapeutic results. The paper surveys the statistical
      data, the risk factors, the preneoplastic ductal lesions, the hormonal
      sensitivity, the possible transdifferentiation in the endocrine and exocrine
      parts and the possibilities for chemoprevention. Hungary is peculiar among the
      European countries because during the last 50 years the incidence of pancreatic
      cancer has displayed a 15-fold increase. Apart from smoking, additional risk
      factors seem to be important, and recently a puzzling association between
      Helicobacter pylori seropositivity and pancreatic cancer was found. First-degree
      relatives of patients with pancreatic cancer are also at increased risk of this
      tumor. The term pancreatic intraepithelial neoplasia (PanIN) seems yet to be
      established, but the dynamics of these lesions needs to be further elucidated.
      Several lines of firmly established data indicate the hormonal sensitivity of
      this tumor, but still an unexplained discrepancy exists between the experimental
      and the clinical results. In addition to the somatostatin analogs, anti-gastrin
      vaccine is being tested. The mixed exocrine-endocrine tumors might suggest a real
      possibility of transdifferentiation between different compartments of the
      pancreas. Finally, the paper outlines the available data about the possibility of
      chemoprevention, including the role of cyclooxygenase inhibitors.

PMID- 14688838
TI  - [Cryptorchism: basic concepts and hormonal therapy].
AB  - The authors analyze the clinical results of 368 cryptorchid testis that received
      intramuscular human chorionic gonadotropin (HCG), at the dose of 50 U/kg once a
      week for 6 weeks. The patients with inguinal anatomical abnormalities or only
      with subtle retractility were excluded. There was a correlation among the
      testicle position, the cryptorchism side, the patient's age at the time of the
      therapy and the results obtained. We observed (i) a delay on child referral; (ii)
      concurrence of cryptorchism and systemic diseases, most of them with genetical
      origin; (iii) better results was obtained in children with retractile testis,
      older than 4 years old and with bilateral cryptorchism. The efficacy of second
      hormonal treatment was only present in retractile testis that showed partial
      response to the first hormonal therapy. It is argued that, although the treatment
      of children under 2 is less effective, the possible prevention of testicular
      lesions for this early intervention justify the hormonal therapy between 6 and 9
      months of life.

PMID- 14688839
TI  - [Use of polimerase chain reaction for neonatal diagnosis of human
      immunodeficiency virus type 1 (HIV-1) perinatal infection].
AB  - The polymerase chain reaction (PCR) was evaluated for its ability to diagnose
      perinatal HIV-1 infection before the development of signs or symptoms of the
      disease in thirty-seven infants (median age of 5.5 days) born to HIV-1 infected
      women. Of 30 children with complete follow up (median of 25 months), 9 (30%) had
      serological and clinical features of HIV-1 infection and 21 (70%) were
      uninfected. Among the infected infants, 5/9 (56%) had positive neonatal PCR tests
      and 4/9 (44%) had negative PCR tests. None of the 21 uninfected children had
      positive PCR tests. The prognosis of HIV-1 disease in infected infants with a
      positive neonatal PCR positive test was similar to that of infected infants with
      a negative PCR test. In spite of not identifying all the infected infants, the
      PCR test is a useful tool for early diagnosis of HIV-1 perinatal infection,
      detecting infected newborns during gestation.

PMID- 14688840
TI  - [BCG test reaction in previously BCG Moreaux-Rio de Janeiro-vaccinated healthy
      children].
AB  - BCG-test reaction was carried out in 91 non-tuberculous children between 2 and 11
      years old, who had received BCG vaccination during the first six months of life
      to critically evaluate the usefulness of this test in Pediatric practice. The BCG
      test profile of the vaccinated group was shown to have a unimodal distribution,
      varying from 3 to 17 millimeters, with a median of 6 millimeters. It was
      demonstrated that the degree of reaction decreases with time. Nevertheless, false
      positives could be expected in a significant percentage when reactions larger
      than 10 millimeters are considered as a cutoff. The specificity can be increased
      using only reactions with diameter equal or greater than 15 millimeters as an
      indicator of tuberculous disease.

PMID- 14688841
TI  - [Quantitative Growth of the human fetal larynx: allometric study between the 9th
      and 38th weeks post-conception].
AB  - The ponderal growth of the larynx was studied in human fetal period between the
      9th and 38th weeks post-conception (w.p.c.). The larynx weight (in grams - g) was
      related with body weight (in grams -g) using the allometric equation Y= ax(b).
      Our results indicated that relative growth of the larynx is allometric negative
      (b= 0.55, p < 0.001). These data are important in estimating the fetal
      gestational age after non-invasive investigation (MR, CT and ultrasound).

PMID- 14688842
TI  - [CFR - Continuous Flow Reviver - a new device for respiratory resuscitation].
AB  - We developed a new device for respiratory revival in order to do it better than
      by using the auto inflating reanimation purse, which is common in this emergency
      situation. This is a portable equipment, handly operated, that controls a
      continuous flow of gas with until 100% of oxygen, that permits to define both
      peak inspiratory pressure and positive end expiratory pressure. Both inspiratory
      and expiratory time can be controlled by the operator during the revive process.
      All process can be effected using endotracheal tube or mask.

PMID- 14688843
TI  - [Biliary tract dilatation and abnormal choledocho-pancreatic ductal junction in
      children].
AB  - Nine children aged between 2 months and 11 years, who had congenital dilatation
      of extrahepatic biliary tract, with or without intrahepatic dilatation, are
      presented. The radiological studies performed in eight patients demonstrated
      abnormal choledochopancreatico ductal junction. Thus, a long common channel is
      formed out of the duodenal wall, leading to a continuous reflux of pancreatic
      juice into the biliary system, chronic inflammation of biliary tract wall,
      fibrosis of muscular layer and finally different types of dilatations. The main
      clinical findings were upper abdominal pain, vomiting, or obstructive jaundice.
      In only one child the dilatation was cystic type and the clinical manifestation
      was palpable abdominal mass. In eight patients the initial diagnosis of biliary
      tract dilatation was made through abdominal ultrasound and in one case by direct
      visualization through emergent exploratory laparotomy. The final confirmation of
      the presence of long common channel was made by preoperative endoscopic
      retrograde cholangiopancreatography or intraoperative cholangiogram. The
      radiologic investigation was not performed in only one case due to bad clinical
      conditions. The surgical treatment indicated to all cases was Roux- en- Y hepatic
      jejunostomy. The late follow up demonstrated that all patients are well and
      assymptomatic.

PMID- 14688844
TI  - [Leiomyoma of the esophagus in children - case report and review of the
      literature].
AB  - The leiomyoma of the esophagus is very rare in children, contrary to what has
      been observed in adults, with only 26 cases reported up to now. In this paper we
      present the case of a 9 year-old child in which the tumor was located in the
      abdominal esophagus, being progressive dysphagia its most important
      manifestation. Diagnosis was done during the surgical procedure, and the
      treatment involved sub-total esophagotomy and pyloroplasty, with ulterior
      esophageal substitution for a colon segment. The only post-surgical complication
      was dumping which resulted from the pyloroplasty. Its symptoms receded with
      appropriate diet. The review of the literature shows that leiomyomas in children
      may be diffuse or located, the former being the more common case (90%). Twelve
      children presented association with Alport's syndrome (nephropathy with
      hematuria, deafness and cataract) while others had hiatus hernia, esophageal
      peptic ulcer and cholelithiasis. In two children the tumor affected the tracheo
      bronchial tree, and in four girls there was vulvar or perianal hypertrophy.
      Finally, there is a rarer kind of tumor in the esophageal muscular layer called
      benign idiopathic hypertrophy, which has been described for six children. Its
      basic histological characteristic is non neoplastic hyperplasia of the cells of
      the internal muscular layer. We conclude that the leiomyomas of the esophagus,
      although rare, must be considered in the differential diagnosis of the
      mediastinal mass and the esophageal stenosis in children.

PMID- 14688845
TI  - [Health and violence in infancy and adolescence].

PMID- 14688846
TI  - [Short stature: a Brazilian social disease].

PMID- 14688847
TI  - [Health and violence in infancy and adolescence].
AB  - This paper deals with the conceptualization and problematization of data on
      violence against infancy and adolescence in Brazil, varying from mortality data
      to the most subtle and concealed forms of domestic violence. It suggests the
      appropriation of such information by the health system and its professionals,
      aiming at the adequacy of their services and policies.

PMID- 14688848
TI  - [The height census of first grade schoolchildren: data quality and cost analysis
      in two Brazilian municipalities].
AB  - The present study describes a first attempt in Brazil to establish a nutrition
      surveillance system based on the systematic collection of the height of children
      entering the first grade of primary school. The strategy used recognized the
      School District as the nuclear institution to operate the system. A quality
      control system showed that trained people were able to collect anthropometric
      data with margin of error compatible with the purposes of the system. Costs were
      low, around 30 cents US per child examined, and they can be further reduced since
      the system is operated in large scale.

PMID- 14688849
TI  - [The height census of first grade schoolchildren: anthropometric data analysis].
AB  - The present study aims at identifying prior areas for nutritional programs
      considering growth scores of children entering the first grade of school. Data
      were obtained through the nutritional surveillance system in a Brazilian city
      called Osasco, Sao Paulo. The analysis was meant to determine the magnitude and
      distribution of growth retardation. In order to establish the nutritional status
      of children the indicator height/age expressed by standard deviation scores (z
      score) was used. Values below -2 s.d. of the reference population median (NCHS)
      were considered height retarded. Children's growth was geographically distributed
      into groups of schools according to height deficit prevalence. Results showed
      marked differences among the schools with deficit prevalence varying between 0
      and 16.1%. This led to the identification of communities with good health and
      nutrition levels, and communities exposed to different levels of malnutrition.
      The level of dissociation was such that it was possible to pinpoint areas and
      micro-areas where social programs and investments are most needed.

PMID- 14688850
TI  - [Clinical and alimentary history of children attending a pediatric
      gastroenterology outpatient clinic with functional chronic constipation and its
      possible complications].
AB  - In order to better understand the natural history of chronic functional
      constipation, a questionnaire was applied to 163 children and infants, before
      beginning standardized treatment. Median age (range) at start was 3 mo(0-108 mo)
      but age at arrival at the Pediatric Gastroenterology Unit was 53 mo(2-146 mo). In
      62.4% of the cases symptoms began before or up to 3 mo after cow's milk
      introduction and rarely around (-/+ 6 mo) toilet training. Possible complications
      appeared progressively, often at preschool or school age or as the first
      noticeable manifestation: recurrent abdominal pain (61.1%), fecal soiling
      (45.4%), fecal blood (35%), enuresis (23.3%), vomiting (19%), urinary infection
      (17.9%), urinary retention (8.6%). Abdominal distension was rarely detected on
      physical examination and was usually discrete. In conclusion, children attended
      in Botucatu begin their constipation at an early age, frequently associated with
      weaning,and important complications may ensue along years. This evolution should
      be avoided by prevention and early treatment of constipation.

PMID- 14688851
TI  - [Comparative study of breastfeeding period among children from internal and
      external day-care centers].
AB  - A cross-sectional study was performed with 137 mothers and their children aged 0 
      35.9 months attending day-care centers (DCC) of Parobe and Tres Coroas, Rio
      Grande do Sul, Brazil. The study analyzed the duration of breastfeeding among the
      children according to DCC in the same mothers' working place (internal DCC) or
      far from mothers' working place (external DCC). The prevalence of breastfeeding
      at 3, 6 and 12 months was 60%, 26% and 7%, respectively. There was a high
      statistically significant association between children in internal DCC and
      breastfeeding over 3 months of life (X(2)= 18.65; p = 0.00001). Mothers with
      children in internal DCC breastfed more during their working period then mothers
      with children in external DCC. The closeness of internal DCC to the working place
      may give the mothers a sense of serenity and safety. There is also more
      availability of the mothers to breastfeed during working time,this way
      maintaining the stimulation to breastmilk production and avoiding the
      introduction of bottle complements.

PMID- 14688852
TI  - [Antral choanal polyp--cause of nasal obstruction in children: report of 12
      cases].
AB  - Nasal obstruction is a common pediatric clinical complaint that involves a great
      number of pathologies (allergic rhinopathy,adenoid hypertrophy, septal
      deformities, infectious sinusitis, tumours, choanal atresia, nasal foreign
      bodies, etc.). Not only the history, and a through physical examination but also,
      the subsidiary exams are of great value in the etiologic diagnostic. Antro
      choanal polyp (Killian's polyp) must be remembered in the differential diagnosis
      of nasal obstruction, when a sinus roentgenogram with unilateral maxillary
      opacification is seen. Clinically, the lesion often protrudes into the
      nasopharynx and in some cases it may even be seen extending into the oropharynx.
      The surgical procedure usually employed is a unilateral Caldwell-Luc antrostomy,
      with oropharyngeal remotion. We present 12 pediatric patients with antral-choanal
      polyps,and discuss history, radiology, nasal/nasopharyngeal endoscopic
      evaluation, considerations about the origin and surgical treatment of choice.

PMID- 14688853
TI  - [Nasal rhinosporidiosis in children].
AB  - Rhinosporidiosis is a rare fungal disease resulting from infection by
      Rhinosporidium seeberi. There seems to be a relationship between the disease and
      agriculture, suggesting that Rhinosporidium lives in soil, and many authors agree
      that water is a necessary medium of transmission. The sites of infection are the
      nose (most common), eye, nasopharynx, penile urethra and external ear. Nasal
      cases generally present obstruction, epistaxis, watery or mucopurulent discharge,
      presence of tumoral pedunculated polypoid mass, generally with septal
      implantation. Histological examination presents characteristic sporangia in large
      numbers and in the submucosa a granulomatous host response. The treatment is by
      surgical excision (recurrence occurs in 10% of cases), and medical treatment used
      diaminodiphenylsulfone or Amphotericin B to avoid recurrent cases. We present a
      case of Rhinosporidiosis in a 10 years-old child, female, with 3 months history
      of nasal obstruction, epistaxis and presence of nasal mass in left nasal cavity
      that was submitted to surgical excision.

PMID- 14688854
TI  - [Xanthogranulomatous pyelonephritis].
AB  - A four years-old boy with Xanthogranulomatous pyelonephritis was surgically
      treated at the Pediatric Surgery Unit of the Santa Casa de Misericordia of
      Maceio. Comments are made upon pathology, pre-operative diagnostic difficulties,
      differential diagnosis, and the rare occurrence in children.

PMID- 14688855
TI  - [Anthropometry and pediatrics].

PMID- 14688856
TI  - [Viral acute diarrhea].

PMID- 14688857
TI  - [Haemophilus influenzae type b infections and its prevention by vaccines].
AB  - Haemophilus influenzae type b (Hib) infections and its prevention by vaccines are
      reviewed. Its prevalence is underestimated, due to technical pitfalls in the
      laboratory and to the difficulties of diagnosing respiratory infections, chiefly
      pneumonia. Taking into account all infections (respiratory, meningitis and
      others), Hib is probably the most important pathogen, compared to S. pneumoniae
      and N. meningitidis. The incidence of Hib meningitis in Brazil is presented and
      risk factors are discussed, as well as the preventive alternatives. The different
      Hib vaccines are analyzed and schedules of immunization with two of them (PRP-T
      and HbOC) are presented. Possible eradication of Hib diseases is discussed.

PMID- 14688858
TI  - [Evaluation of body composition by means of anthropometric measures in obese and
      non obese adolescents from two socioeconomic levels].
AB  - Anthropometric measures of 120 female adolescents were analyzed, 60 of them from
      a low socio-economic level (LSEL),and 60 from a high socio-economic level (HSEL),
      with 30 obese and 30 non-obese in each group, in an attempt to verify differences
      between the socio-economic levels in relation to the body-composition and the
      distribution of fat throughout the body. The weight,height, upper arm
      circumference and 4 skin folds (triceps, biceps,subscapular and suprailiac) were
      measured, and the arm muscle area, arm fat area and percentage of body fat were
      estimated. Those who were obese from LSEL presented an average height lower
      (p<0.05) than the obese from HSEL, and a greater proportion of this group
      presented a height deficit for their age. The arm muscle area was greater
      (p<0.05) in the obese from HSEL, but the percentage of body fat was similar in
      the two groups as well as the measures of the isolated skin folds. The increase
      in fat in the obese from LSEL, when compared with the non-obese, was 2.8 times
      greater than the muscle. In the HSEL, this increase was 1.3 times greater. It was
      concluded that the obese from both socio-economic levels presented different
      types of obesity in relation to body composition,but were similar in relation to
      body fat distribution.

PMID- 14688859
TI  - [Clinical aspects of children presenting specific IgM antibodies to
      cytomegalovirus by immunofluorescent test].
AB  - Clinical data observed in 25 children presenting IgM specific antibodies to
      cytomegalovirus (CMV) by immunofluorescent test are reported. The children were
      grouped by the presented clinical picture in: neonatal hepatitis, mononucleosis
      syndrome,pneumonitis, neurologic disease, ocular abnormalities, and
      thrombocytopenic purpure. Clinical aspects of CMV infection were analyzed and
      compared with data reported in the literature. CMV infections can involve
      multiple organs and this viral disease must to be considered on differential
      diagnosis of many infectious diseases.

PMID- 14688860
TI  - [Prospective study of rotavirus infections in Belem, Para, Brazil: clinical and
      epidemiological features].
AB  - A prospective study of acute diarrhoeal diseases was carried out from April 1990
      to September 1992 with the purpose of assessing the immunogenicity, safety and
      efficacy of a Rhesus-human reassortant rotavirus ("RRV-TV") vaccine, involving
      540 children living in Belem, Para, Brazil. As half of the children received
      placebo, this trial provided the opportunity of broadening the knowledge on both
      clinical and epidemiological aspects of rotavirus infection in the Amazon region.
      There were 2,789 diarrhoeal episodes during the above mentioned period, of which
      86 (3.1%) associated with rotavirus; serotype 1 was the more prevalent,
      accounting for 67.9% of serotyped strains. Rates of 5.9 and 0.2 episodes of
      diarrhoea per child/year were noted for all cases and the rotavirus-related ones,
      respectively. This agent was the only pathogen found in 70.9% of the 86 rotavirus
      related episodes of acute diarrhoea, whereas the most frequent associations
      involved Giardia intestinalis and enteropathogenic Escherichia coli, accounting
      for 7.0% and 11.6% of mixed infections,respectively. The monthly rates of
      rotavirus-related episodes of diarrhoea ranged from 0.8% to 9.6%, reaching the
      highest peaks during the dry months of the year. Means of clinical severity
      scores of 9.4 and 5.3 were recorded for the rotavirus-related episodes of
      diarrhoea and those of other aetiology, respectively.

PMID- 14688861
TI  - [Hypertension: retrospective study in children from a pediatric nephrology unit].
AB  - 300 hypertensive children, from newborn to 18 years old,were studied,
      retrospectively, from 1975 to 1992, 105 from those lost for follow-up. In 244 the
      diagnosis of the primary disease, predominantly glomerulopathy, was established.
      122 had chronic renal failure (CRF). From them, 74 arrived at end stage renal
      disease (ESRD) and 13 have been transplanted. From 12 submitted to surgical
      treatment, hypertension has been controlled in 8. 54 died, 48 with CRF and 38
      with ESRD. Difficulties in controlling those patients are discussed, mainly
      therapy diet, the use of hypotensive drugs on dialysis treatment. Our conclusion
      is for the necessity of a precocious diagnosis for hypertension and primary
      diseases, of a trained interprofessional team as well as availability of adequate
      equipment to children, mainly for dialytic therapy. For many of these children,
      renal transplantation is the only definite therapy.

PMID- 14688862
TI  - [Clinical, laboratorial, and therapeutic aspects of 46 children with Henoch
      Schonlein purpura].
AB  - Forty-six children with Henoch-Schonlein purpura were studied.Their clinical
      manifestations included palpable purpura in 100%, subcutaneous edema in 30%,
      arthritis/arthralgia in 78%, gastrointestinal involvement in 56% and renal
      abnormalities in 30%. Serum IgA was elevated in 12%, ASLO titers in 27% and
      microscopic hematuria and proteinuria were detected in 30% of the children,
      including two with nephrotic syndrome. Treatment with non-steroidal
      antiinflammatory drugs or corticosteroid was indicated in 43% of the children.
      Recurrence of the disease was observed in 22% and the prognosis seems to be
      related to severity of renal involvement.

PMID- 14688863
TI  - [Three successive rotavirus infections in a child from Belem, Brazil].

PMID- 14688864
TI  - [Kwashiorkor as early clinical manifestation in a baby with cystic fibrosis].
AB  - A case of cystic fibrosis in a baby presenting Kwashiorkor (edema,
      hypoalbuminemia and anemia ) is described. This is a very unusual presentation,
      easily attributed to unfavourable socio-economic conditions of the population,
      and classically considered a marker for severe pulmonary disease during the first
      year of life. Presence of severe pancreatic insufficiency is related to genotype
      delta F508 (homozygote) but colonization and early infection with Staphylococcus
      aureus and Pseudomonas aeruginosa in this baby requires further study. Cystic
      Fibrosis is the most frequent genetic disease among Caucasians, and early
      diagnosis has prognostic implications, agreed upon by all.

PMID- 14688865
TI  - [Surfactant therapy for respiratory distress syndrome in preterm neonates].

PMID- 14688866
TI  - [Prenatal and neonatal hearing].

PMID- 14688867
TI  - [Breast-feeding: how and why to promote it].
AB  - Breastfeeding promotion must be seen as a priority for the improvement of health
      and quality of life of children and their families. The strategies should vary
      according to the population, its culture, habits, beliefs, socio-economic level
      and other characteristics. Nevertheless, awareness of the importance of
      breastfeeding is crucial in any strategy. This review article aims to increase
      this awareness among health professionals. Epidemiologic evidences of the
      importance of breast feeding for the mother and child health are addressed.
      Emphasis is given to the impact of breastfeeding on infant mortality, morbidity
      and nutritional status, as well as on birth spacing. Further, this article
      discusses some breastfeeding promotion activities, specially educational programs
      for health professionals, pregnant women, parturients and general population.
      Changes in hospital routines, mass media,milk substitute marketing, protection of
      working mothers and community activities are also addressed.

PMID- 14688868
TI  - [Surfactant replacement therapy: a multicentric trial comparing two dosage
      approaches].
AB  - This is an interim analysis of a multicentric trial that took place in 7 Neonatal
      Units to compare two initial doses of exigenous pulmonary surfactant (100 mg/kg
      and 200 mg/kg of phospholipids)by using a porcine surfactant for the treatment of
      very severe Hyaline Membrane Disease. The initial higher dose produced better
      oxigenation of arterial blood, reducing the time in high oxygen
      concentrations,while retreatments were necessary in less than half of the infants
      receiving 200 mg/kg as initial dose. The protocol of this study allowed the
      administration of additional doses only when FiO(2) was equal or greater than
      0.40 instead of > 0.21, as in a large study recently published, where the same
      initial doses were given. This resulted in more than 40% reduction in the amount
      of surfactant administered,with apparently similar clinical outcome.

PMID- 14688869
TI  - [Incubator noise evaluation].
AB  - Measurements of noise produced by incubators and their associated live support
      equipment (oxygen central network)has been performed. In 33.3% of the incubators
      the noise level was above the standard specification (60 dB(A)) according to
      International Standards. Without live support equipment, the mean noise level was
      58.9 dB(A). Using live support equipment with oxygen flow of 3,5 and 81/min, the
      mean noise level has increased to 60.5 dB(A) (P=0.53), 60.9 dB(A) (P=0.39) and
      67.2dB(A) (P=0.017) respectively, showing a remarkable influence of the central
      gas distribution on the incubator internal noise. In 82.5% of the incubators
      using a plastic box over the infant's head an injecting moist oxygen/compressed
      air the noise level was above the standard specification; when oxygen proportion
      was increased the internal incubator noise level increased as well showing a
      statistically significant relationship between them. Measurements of impulse
      noise produced by incubators lateral access door handling has shown a 107.0 dB
      (F).

PMID- 14688870
TI  - [Pulmonary mechanics in the full-term newborn].
AB  - The objective of this study is evaluate the pulmonary function in full term
      newborn infants, comparing classic with non-invasive techniques. We describe the
      pulmonary function laboratory and software developed at Instituto Fernandes
      Figueira. We studied 10 healthy full-term newborn infants (birthweight 3.260 g + 
      460 g) Occlusions were performed at inspiration end and during expiration which
      allowed us to calculate values for total pulmonary resistance (TPR) and total
      pulmonary compliance (TPC). Esophageal pressure was measured with a water filled
      catheter positioned in the lower third of the esophagus, to obtain lung
      resistance (RL) and compliance (CL). All signals were digitized at 60 Hz into a
      microcomputer for further analysis. Mean results of our study are: CL= 1.78 + -
      0.36 ml/cm H(2)O/kg, TPC= 1.12 + - 0.27 ml/cm H(2)O/kg and TPR= 16 + - 4 cm
      H(2)O/l/seg/kg. Our values are very similar to the ones in the current
      literature.

PMID- 14688871
TI  - [Use of pacifiers in children: patterns and determinants].
AB  - Although pacifiers are commonly used by Brazilian children and are potentially
      harmful, there are no studies about their patterns and determinants. These were
      investigated in a cross-sectional study of 354 children under two years of age
      living in two slum areas of Pelotas, southern Brazil. Most children (79%) were
      pacifiers users, 15% had never used them, and 6% had used them in the past. Among
      users, 38% spent most of the time sucking a pacifier. For two-thirds of the
      children, pacifiers were offered on the very first day of life. Pacifier use was
      most common among younger children,among those of low-schooling mothers and among
      non-breastfed infants.

PMID- 14688872
TI  - [Short stature and Turner syndrome: an association more frequent than expected].
AB  - Turner syndrome is a well-known cause of proportionately short stature in girls,
      but its frequency among these patients must vary in different populations. In
      Brazil, the cytogenetic study of 38 short girls without psychoneuromotor
      retardation, and without taking into account the presence or absence of
      dysmorphic signs, revealed that at least 1:8 had Turner syndrome. This is an
      unexpectedly high frequency ina population which is largely subject to adverse
      environmental conditions leading to growth deficiency.

PMID- 14688873
TI  - [Odontogenic osteomyelitis of the maxillary bone].
AB  - The authors present the case of a two-year and eleven month old boy with gray
      skin who had chronic focal suppurative osteomyelitis diagnosed by clinical,
      surgical and histopathological examination. Its probable dental origin is
      commented as well as its therapeutics and evolution.

PMID- 14688874
TI  - [Subcutaneous fat necrosis or adipo necrosis in the newborn. Report of a case].
AB  - A case of subcutaneous fat necrosis that occurred at Hospital e Maternidade Sao
      Luiz is described. A brief review of the literature is made and the authors
      verify that the risk group for fat necrosis is constituted by full-term newborns
      who experienced fetal distress. It is shown that hypercalcemia is frequently
      present in this condition and its symptomatology,etiology, and treatment are also
      discussed. Finally, the authors suggest the close follow up of these patients
      until 16 weeks of life to try to identify the laboratorial and clinical signs of
      hypercalcemia promptly.

PMID- 14688875
TI  - [Growth through quality].

PMID- 14688876
TI  - [Pain in the newborn infant].

PMID- 14688877
TI  - [Tuberculosis--an old and ever present problem].

PMID- 14688878
TI  - [Pneumococcal vaccine: overview about the protective efficacy in different high
      risk groups and new progress in the development of a conjugate pneumococcal
      vaccine].
AB  - The author presents a review about the protective efficacy of polyvalent
      pneumococcal polysaccharide vaccines in different groups at high risk for severe
      pneumococcal infection and the difficulties in the development of a conjugate
      pneumococcal vaccine capable of offering protection to younger children.

PMID- 14688879
TI  - [Pain in intubated and ventilated preterm neonate: multidimensional assessment
      and response to fentanyl analgesia].
AB  - The purpose of this study was to verify if multidimensional pain assessment,
      performed through physiologic and behavioral measures, together with this
      assessment modifications in response to opioid analgesia, could determine the
      presence of pain in preterm neonates (PT) under mechanical ventilation through
      endotracheal tube (ETT). The population consisted of 22 PT with gest. age < or =
      32 weeks, between 12-48 h of life. All of them had an ETT and an umbilical
      arterial line in place and were on mechanical ventilation. The infants were
      admitted at Sao Paulo Hospital NICU from 11/91 to 11/92. Neonates' observation
      was performed in three 10 minute periods: prior medication (Pre-Analgesia), 30
      min (Analgesia 1) and 60 min (Analgesia 2) after the injection of either fentanyl
      (3 mcg/kg) or sterile water (0.2 ml). In each period an arterial blood gas was
      drawn and the following parameters were recorded: ventilator settings, heart
      rate, non-invasive blood pressure and 02 saturation. Behavioral measures were
      also observed: ATTIA scale, MCGRATH scale and GRUNAU & CRAIG pain facial
      features. In Pre-Analgesia and Analgesia 2 periods, blood samples were obtained
      and serum cortisol, serum GH, plasmatic glucose and lactate were measured.
      Patients were filmed through the study and behavioral measures applied for each
      patient film. The research author was blind to the medication until final
      results. High levels of serum cortisol, serum GH and plasmatic lactate were
      present in the whole study population prior to medication. They also presented
      low ATTIA scale scores and pain facial mimic, as per MCGRATH and GRUNAU & CRAIG
      evaluations. Patients that received fentanyl exhibited decrease in the maximum
      heart rate, decrease in serum cortisol, increase in serum GH, stability in blood
      glucose levels, better ATTIA scale comfort scores and less pain facial movements.
      None of these occurred in neonates that received placebo. Critically ill
      intubated and ventilated PT do feel pain, as assessed by this multidimensional
      evaluation. Analgesia should be considered in order to treat these patients'
      pain.

PMID- 14688880
TI  - [Can the Mantoux test be used in BCG vaccinated children?].
AB  - This prospective trial was realized in 371 children previously vaccinated with
      BCG in the first month of life in whom the Mantoux tuberculin test was done and
      read 48-72 hours afterwards. Among 371 BCG-vaccinated children, 106 (28.57%) were
      Mantoux reactive, 10 of whom with clinical tuberculosis. There was no
      statistically significant difference in the tuberculin test between the control
      group (59 non-BCG-vaccinated children) and 180 vaccinated children, considering
      those under 6 years old. When we compared by age, we verified that just 36.36% of
      the children at the age 2 reacted positively to PPD.

PMID- 14688881
TI  - [The effect of the supernatants of enteropathogenic Escherichia coli strains on
      the intestinal transport of sodium in rats "in vivo"].
AB  - We studied the effect of the supernatants of 2 to 5 samples of one of the
      following serotypes of EPC: 026:H, 086:H34, 0111:H-, 0119:H6, 0126:H21,
      0128ab:H35 and 0142:H-, isolated from the stools of infants with gastroenteritis.
      We also studied 3 samples of the serotype 0157:HNT, that produces the Shiga-like
      toxin. The following control solutions were selected 1-SC1 (glucose-saline
      solution); 2-SC2 (TSB broth culture solution); 3-SC3 (E.coli K12 711 culture
      supernatant, a non enterotoxigenic serotype). These solutions were perfused in
      the small intestine of rats "in vivo" and sodium transport was determined. The
      comparison among the 3 control solutions revealed that there was always sodium
      absorption, but there was a difference in the intensity of the transport (SC1
      >SC2 and SC3). The serotypes 0111:H-, 026:H-, 0126:H21, and 0142:H2, as well as
      the serotype 0157:HNT, induced sodium secretion and these values were
      significantly different in comparison with the 3 control solutions. On the other
      hand, the serotypes 0128ab:H35 and 0119:H6 induced sodium secretion but the
      differences were only significant in comparison with the SC1 and SC2, and SC1,
      respectively. The supernatants of the serotypes investigated provoked an
      important derangement in sodium transport probably due to the presence of an
      enterotoxin.

PMID- 14688882
TI  - [Intestinal transport of coconut water sodium and glucose in rats "in vivo"].
AB  - The chemical composition of coconut water shows a great variability during its
      maturational process and in no instance this fluid can be considered as an oral
      rehydration under scientific basis. The jejunal transport of water, sodium and
      glucose was studied in rats in vivo with coconut water during the different
      stages of maturation of the fruit. There was water absorption (mean = 1.07 -/+
      0.45 microl/min/cm), sodium secretion (mean =-169.04 -/+ 29.06 microEq/min/cm)
      and glucose absorption (mean = 5212.70 -/+ 2098.47 microg%/min/cm) in all the
      stages studied. This study demonstrates that sodium secretion impedes considering
      coconut water a rehydrating solution.

PMID- 14688883
TI  - [Rigid respiratory endoscopy in children].
AB  - From march 1989 to march 1992, three hundred and fifty six respiratory
      endoscopies were performed at "Hospital da Crianca Santo Antonio", Porto Alegre,
      Brazil. The endoscopies were performed with a rigid pediatric bronchoscope and
      under general anaesthesia. The most common indications for endoscopy were stridor
      (52%), suspected foreign body (16%), atelectasis (16%) and difficult tracheal
      extubation (8%). The most frequent diagnosis were laryngomalacia (36%) and
      subglottic stenosis (6%) in the glottic and subglottic areas, and foreign body
      (9%) and tracheomalacia (7%) in the tracheobronchial area. Normal endoscopy was
      observed in 54 (21%) of the children. Only three slight complications of the
      endoscopy were observed. Two patients presented bradycardia during the exam, and
      the third needed tracheal intubation due to post-endoscopic subglottic edema.
      This confirms that the rigid endoscopy in children is efficient and has no
      serious complications.

PMID- 14688884
TI  - [Non-reactive tuberculosis: a clinicopathological study].
AB  - The authors report a case of non-reactive tuberculosis diagnosed at autopsy. This
      is a very rare type of clinical presentation of tuberculosis and is usually
      associated with immunosuppression and gross abnormalities of haemopoiesis.

PMID- 14688885
TI  - [Ceftriaxione associated biliary lithiasis in newborns-report of two cases].
AB  - The occurrence of biliary calculosis as a complication of the use of ceftriaxone
      was first described in an 18-year-old patient with chronic granulomatosis. Since
      then many reports have been published on this type of complication both in
      children and in adults, but until the present moment, this complication had never
      been reported in pre-term neonates.The authors describe two cases of biliary
      calculosis associated with the use of ceftriaxone in preterm-newborns,
      emphasizing that due to the frequent use of this type of antibiotic in neonatal
      I.C.U., routine ultrasonographic control exams should be performed to diagnose
      this possible complication in all neonates receiving ceftriaxone.

PMID- 14688886
TI  - [So much to hate, and so little time].

PMID- 14688887
TI  - [AIDS in childhood: basic guidance for attending].
AB  - The pandemic expansion of AIDS demands that all health care staff and
      institutions are prepared to diagnose and control this disease. The HIV virus
      destroys the immune response and causes a series of other organ and system
      dysfunctions, leading to diverse clinical manifestations. This article reviews
      the pathophysiology, clinical manifestations, diagnosis, treatment and prevention
      of HIV infection. The role of the health care worker as an educator is also
      reviewed.

PMID- 14688888
TI  - [Influence of the different types of room on newborns during breastfeeding].
AB  - The present study was developed in the CMSCVL, which is a primary medical
      attendment clinic for children and pregnant women, during the period of
      01/10/1980 to 31/12/1984, containing 132 children. The study was longitudinal and
      respective and the two distinct groups of children may be established, differing
      in accordance to the hospital stay period of postpartum, in rooming-in or
      traditional nursery. After the statistic analysis of all the variables involved
      in the study, the only variable that really resulted was the site of internation
      during the postpartum period. Although these exist a tendency to the greater
      frequency of breast feeding in the group that utilized the rooming-in, the
      statistics analysis showed that this difference is not significant. However
      should consider the important paper carried out by the CMSCVL, in the
      encouragement of the practice of the breast-feeding, what may have homogenized
      the two groups. The medium time of weaning found for the population of 132
      children studied was 8 months, while for those children that utilized the rooming
      in is system was 10 months and for those that stayed in the traditional nursery
      it took 9 months. The motives of weaning were also identified for the studied
      population that showed similarity to other published projects.

PMID- 14688889
TI  - [Reflections on the causes of early weaning observed through group dynamics in
      groups for encouraging breastfeeding].

PMID- 14688890
TI  - [Some psychological consequences in children cured from cancer. A parent's view].
AB  - This is a qualitative study, preliminary considered, whose objective is listening
      to children's parents who have carried out the cancer treatment trying insights
      about the meanings which relate to lived experiences by and with their children.
      From the question: "How is your kid, since he became free from the disease and
      treatment?" emerged interesting themes of cirunscrit problematic on the
      psychosocial area.

PMID- 14688891
TI  - [Evaluation of child care program in the COHAB Pestano primary health center].
AB  - This article describes an evaluation method that involves the health team. This
      method is fast and cheap. The major objective is the use of the health team to
      improve the health attention quality. This method gives information about
      children inscription, consults.

PMID- 14688892
TI  - [Management of tricuspid atresia in neonates. Report of three cases and review of
      literature].
AB  - The present article describes the management of three neonates with tricuspid
      atresia and duct dependent pulmonary circulation referred to the Instituto de
      Coracao de Pernambuco in November 1992. A brief literature review of the
      condition is added. Full diagnosis was established with echocardiography at the
      neonatal ICU; all of them were intubated, mechanically ventilated and started on
      PGE1 and Dopamine infusions. Within 10h to 24h of hospitalization, all were
      submitted to surgery. One patient died on the third postoperative day the other
      two were discharged in good clinical condition. Despite the small our experience
      shows that clinical and surgical management of tricuspid atresia with duct
      dependent pulmonary circulation can reach satisfactory results in our region
      providing that early diagnosis of cyanotic heart disease is established by the
      pediatrician with timely transferal of the neonate to a reference center in
      paediatric cardiology.

PMID- 14688893
TI  - [Evaluation of the psychoaffective development of adolescents aged 15-18. A study
      on adolescents in the town of Botucatu, SP-aspects of sexuality].
AB  - The authors present data obtained from the analysis of a questionnaire regarding
      sexuality among 1,437 adolescent students in the Botucatu municipal district. The
      student's age varied from 15 to 19 years. The results demonstrate the evolving
      characteristics of the student's sexuality and suggest that sexual orientation
      and guidance should be part of the child and adolescent educational process. The
      authors pointed out that the members of Health care team should stimulate the
      discussion of sexuality while providing medical advice.

PMID- 14688894
TI  - [Acute infant diarrhea associated to Cryptosporidium sp., in the city of Recife].
AB  - From February through June 1990 the frequency of Cryptosporidium sp. among 156
      infants with acute diarrhea and 80 controls were analyzed. The study was carried
      out in the Hospital Geral de Pediatria do Instituto Materno-Infantil de
      Pernambuco. Cryptosporidium sp. was detected in 6.4% of infants with diarrhea; it
      was not found in the controls. The clinical patterns and the disease evolution
      were the same in the infants Cryptosporidium-positive and Cryptosporidium
      negative.

PMID- 14688895
TI  - [Mixed papillary follicular carcinoma of the thyroid gland in childhood. Report
      of a case].
AB  - The authors have reported a case of childhood Thyroid Carcinoma at a Pediatric
      Service. This report has been justified since this is an uncommon pathology in
      children and a very unusual clinical picture for children. The etiology and
      diagnostic have been reviewed by the authors. The clinical investigation as well
      as the clinical course of the disease has been present. The literature for
      thyroid cancer in children has also been reviewed. The need for a careful
      investigation in children with unusual radiologic finding has been emphasized;
      being the thyroid carcinoma metastasis diagnosis one of the possibilities.

PMID- 14688896
TI  - [Use of alcoholic beverages by children: a not yet investigated phenomenon].
AB  - The essay discourses on the ethanol prescription to children, their dependence
      and the scientific data related to the social abuse. The toxic effects, social
      and economical perspectives are well exemplified on the follow-up of a child of
      three years old in a university hospital during eighteen months. At the end, the
      prevalence of such practice is highlighted as essential for preventive approach
      on public health.

PMID- 14688897
TI  - [The abused and neglected child].
AB  - The study of mistreatment of the child and adolescent, with its historical,
      social and cultural roots, grow amidst conceptual and methodological difficulties
      which oppose a more realistic understanding of the problem. The physical and
      emotional consequences, long-term and immediate, are to a great extent, known.
      However, an attempt to understanding minimize such phenomenon faces great
      obstacles. At present, the interdisciplinary practice is a possible solution.

PMID- 14688900
TI  - [Risk factors of stillbirths in Fortaleza: a case-control study].

PMID- 14688901
TI  - [Promoting and supporting breast-feeding: Baby Friendly Hospital Initiative].
AB  - The objective of this article is to analyze the "Baby Friendly Hospital
      Initiative" in Brazil. This initiative, that intends to support, protect and
      promote breast-feeding, has been proposed in a meeting in Florence, Italy, in
      1990, promoted by OMS and UNICEF. The basic goal of this initiative is to
      mobilize health professionals and hospital or maternity workers to change their
      routines and conducts in order to prevent early wean. Health establishments are
      evaluated based on the "Ten steps for the success of breast-feeding" (a group of
      goals created in the same meeting by a group of health and nutrition
      specialists). In Brazil, the evaluation is coordinated by PINAM, and carried out
      in two steps. If approved, the hospital receives extra payment for childbirth
      assistance and prenatal follow-up. Up to now 64 hospitals in Brazil have received
      approval. Data from PNIAM show that the implementation of the ten steps and the
      encouragement of breast-feeding resulted in significant increase of its levels in
      Brazil.

PMID- 14688899
TI  - [Risk factors for low birth weight in a rural community in southern Brazil].

PMID- 14688902
TI  - [Risk factors for low birth weight in a rural community in southern Brazil].
AB  - This paper reports a study assessing risk factors for low birth weight (LBW),
      preterm and intrauterine growth retardation (IUGR) in a sample of 936 mothers who
      delivered babies in the Cangucu Hospital, a rural area of southern Brazil.
      Traditional risk factors for delivering LBW, preterm and IUGR were examined. The
      relative importance of the risk factors was studied through risk calculation and
      logistic regression analysis. Some risk factors for LBW such as low maternal
      education and number of prenatal consultations were not associated with the risk
      of delivering babies in any of the three risk groups. Hospitalization during
      pregnancy and maternal age less than 20 years were confirmed as risk factors for
      LBW. In the preterm group, low maternal weight and hospitalization during
      pregnancy showed significant association after control for confounders. The
      results suggest that there are specific targets for intervention in each of the
      three groups, and some traditional risk factors must be redefined according to
      the characteristics of each population.

PMID- 14688903
TI  - [Risk factors of stillbirths in Fortaleza-Brazil: a case-control study].
AB  - Stillbirths are a common event in areas where reproductive health care is poorly
      delivered, such as the Northeast region of Brazil. This case-control study aimed
      to identify risk factors associated to foetal deaths occurred in a major
      obstetric facility of Fortaleza, 1.7 million inhabitants, Northeastern Brazil.
      125 stillborn foetus over 20 weeks of gestation (cases) were compared to 250
      healthy newborns (controls), in relation to socioeconomic, reproductive,
      behavioral and morbidity characteristics of their mothers. Crude and adjusted
      Odds Ratios were then calculated. After adjustment for confounders, the following
      characteristics of the mother remained as risk factors for stillbirths, with OR
      statistically significant at the 95% level: attending <5 antenatal consultations
      during pregnancy (OR=3.30; CI=1.92 - 5.07 ), illiterate mother (OR=3.30; CI=1.84 
      5.92 ), mother's age above 19 (OR=2.73; CI=1.42 - 5.24 ), monthly family income
      of 1 minimum wage or less (OR=2.12; CI=1.03 - 4.35 ) and severe illnesses or
      complication during pregnancy (OR=1.75; CI=1.01 - 3.03 ). Inadequate attendance
      to antenatal care consultations was the risk factor most strongly associated to
      stillbirths. Similarly, it was the condition most amenable to change in a short
      term, among those identified as risk factors.

PMID- 14688904
TI  - [Perinatal factors related to the morbidity and mortality of newborns in nine
      neonatal care units in the city of Sao Paulo].
AB  - This study was carried out in nine hospitals in the city of Sao Paulo, in 1991
      (between July 1 and November 30), when 10,235 live children were born. The aim of
      this study was to analyze the characteristics of the 1975 pathologic newborn
      (PNB) who were put into those neonatal care units (NCU) of the hospitals; besides
      that, the most common morbidity conditions, breast feeding prevalent and
      therapies were studied. It was calculated the odds ratio, its confidence interval
      and the c(2) test in order to evaluate the association between the variables and
      the death of the PNB. The results have demonstrated that the low weight PNB
      lethality (especially those with weight <1500 g) was higher than those PNB whose
      weight was > or = 2500 g. The lethality for both premature PNB and small for
      gestational age PNB was higher than the other categories of babies. The PNB with
      hypoxia until the 5th minute had the worst prognostic: their lethality was 10
      times higher than the other category. The PNB who had Apgar < or =7 until the 5th
      minute had twice as much lethality when compared with PNB who had Apgar < or =7
      just until the 1st minute. Conventional therapies have been used and only 25.4%
      have received breast feeding. Several risk factors (maternal, delivery, newborn)
      were associated with the PNB mortality, as well as most of the morbidity
      conditions. Those factors reflect the perinatal assistance in our environment.

PMID- 14688905
TI  - [Weight gain of very-low-birth-weight newborns].
AB  - The objective of this investigation was to study weight changes at the postnatal
      period of 61 very-low-birth-weight newborns who survived out of 114 alive
      newborns from October 93 to October 94. They were grouped according to their
      birth-weight (750-999 g, 1000-1249 g, 1250-1499 g), gestational age (<30 weeks,
      30-31 weeks, 32-33 weeks, > or = 34 weeks) and adequacy of weight for gestational
      age (AGA, SGA). The weight variation was expressed in percentage according to the
      birth-weight and in g/kg/day. In all groups there was an initial loss of weight
      within the first five days of life. The groups which were smaller than 1250 g and
      younger than 30 weeks presented the greatest loss of weight and the longest
      period to recover it. The recovery of birth occurred similarly in all groups,
      with an average of 15 g/kg/day. The difference between the SGA and the AGA may be
      attributed to the groups' different gestational ages. Being aware of the way the
      newborns grow will permit early detection of deviations which may affect their
      quality of life.

PMID- 14688906
TI  - [Intranasal azelastine in the treatment of perennial allergic rhinitis in
      children].
AB  - Twenty-five patients (5-15 years old) with perennial allergic rhinitis (PAR) for
      at least one year were treated with intranasal azelastine. The study was
      conducted in two separate occasions. In the first study, in a special prepared
      room, the patients underwent Active Anterior Rhinomanometry (AAR). Twenty minutes
      later, after 2 drops of saline installed in each nostril, the Total Nasal
      Resistance (TNR) and Total Nasal Conductance (TNC) were measured. This was
      followed by the intranasal application of azelastine (0.14 mg/nostril ) and the
      TNR and TNC were measured at 15,30,60,90 and 120 minutes. At the end of this
      period, a topical vasoconstrictor (fenoxazoline 0.05%) was instilled and TNR and
      TNC measured after 15 and 30 minutes. The patients were discharged with a
      prescription of intranasal azelastine, same dose, for 14 days, with diary cards.
      Clinical evaluation and clinical score were performed at days 3,7 and 14. There
      were no changes in TNR and TNC after the acute and prolonged (14 days) use of
      azelastine, which was observed after the use of fenoxazoline. Clinical scores
      (physician and patient), according to the diary card, were significant for
      itching and sneezing after 7 days of treatment. Intranasal azelastine is useful
      for the therapeutic management of PAR, mainly in those for whom nasal blockage is
      not important.

PMID- 14688907
TI  - [Non-Hodgkin's lymphoma in children: analysis of nutritional status and other
      prognostic factors].
AB  - The influence of the nutritional status and other prognostic factors on the
      survival of 43 children with non-Hodgkins lymphoma was investigated in a
      retrospective study. The median age was 5.3 years. Most children had advanced
      abdominal disease and Rappaport's diffuse undifferentiated type. The median time
      of follow-up was 4.7 years (0.1 to 12.9 years). The estimated probability of 5
      and 10-year survival was 69% -/+ 7%. The unfavorable prognostic factors were
      metabolic disturbances, treatment with the LSA(2)L(2) protocol, unresectable
      tumoral mass, age below 2 years and stage III or IV disease. The nutritional
      status did not influence the outcome. Eight children died within the first days
      of hospital admission; five had extensive abdominal Burkitt's type lymphoma with
      elevated uric acid concentration. All had been treated with nonfractionated high
      dose cyclophosphamide in the first four years of the study and had metabolic
      complications which probably led to their death. The authors conclude that the
      overall survival is similar to that reported in the literature; the nutritional
      status did not influence the outcome; the high frequency of early death in the
      first days of treatment was probably due to the toxic-metabolic effects of
      nonfractionated high-dose cyclophosphamide, but other adverse factors were
      clearly associated.

PMID- 14688908
TI  - [Predictive score of infectious complications on kalazar of child].
AB  - The reports on fifty four children under thirteen years old with visceral
      leishmaniasis were evaluated to find a prediction criterion for the risk of
      infectious complications on the course of this disease. The children were divided
      into two groups according the presence or absence of infectious complications.
      The statistic model adopted was the Fisher Discriminant Analysis by the method of
      Wilks. The variables presenting a good discriminant power were: heart rate, white
      blood cells count, blood lymphocytes count, platelets count and glutamic
      oxalacetic transaminase. The discriminant score for the risk of infectious
      complications in each case was estimated by means of the defined discriminant
      function, resulting in 75.93% of correct classification in each group, with
      80.60% of correct prediction of the risk. This procedure is then valid as a
      prediction instrument for infectious complications on the course of kalazar in
      children and may contribute to improve the quality of treatment of this disease.

PMID- 14688909
TI  - [Cytomegalovirus infection in an infant with epidermolysis bullosa].
AB  - The authors report and discuss the case of an infant bearer of Epidermolysis
      Bullosa who was affected by acquired Cytomegalovirus infection.

PMID- 14688910
TI  - [Intravaginal perinatal torsion of the spermatic cord].
AB  - Spermatic cord torsion is an urologic emergency that requires urgent evaluation
      and possibly emergency surgical management. In a neonate it occurs during
      testicular descent and is usually due to an extravaginal torsion, where the
      testis and sperinatic cord twist. We present a case of intravaginal testicular
      torsion in a neonate. In this situation, as the anomalous implant of the tunica
      vaginalis can occur bilaterally, it is important to fix the contralateral testis
      in order to prevent late torsion of this gonad.

PMID- 14688911
TI  - [Lead poisoning: an important pediatric problem].

PMID- 14688912
TI  - [Outpatient treatment of the child with complicated urinary tract infection].

PMID- 14688913
TI  - [Bronchodilators in asthma: bypassing controversies].
AB  - Inhaled bronchodilators are used in acute asthma for relief of airway
      obstruction. Continuous monotherapy with beta 2 adrenergic can increase
      hyperresponsiveness because these drugs do not control inflammation. Asthma
      mortality and morbidity have been related to an increased beta 2-agonists use.
      Epidemiologic data however do not show a cause/effect relationship. Until
      controversies are cleared on, beta 2-agonists should be used for relieving acute
      asthma attacks, for preventing exercise-induced bronchospasm and eventually on an
      as needed basis. Long acting beta 2-agonists can be effective in moderate/severe
      asthma. Daily short acting beta 2 use by inhalation, a partial clinical response
      and its overuse in acute asthma suggest the need for antiinflammatory treatment.

PMID- 14688914
TI  - [The children of the Valley of Death--reflections on terminal children].
AB  - The author ponders on the role of the pediatrician facing the death issue and its
      philosophical and existential implications. The author also ponders on the death
      issue in todays culture, as well as the transformation undergone by exequies, and
      modern man's death in the loneliness of emergency rooms, where he dies
      technologically well assisted but in a lonely, impersonal environment far away
      from his loved ones, and deprived of the sheltering warmth of his home. The
      author considers the difficult task of revealing a diagnosis and prognosis of a
      terminal illness to the patient's family and to the patient himself. He studies
      the several stages of such a revelation and offers an extensive bibliography of
      the literature concerning the issue. He judges the terminal patient's family's
      different reactions to the revelation, from the search for impossible miracles
      through wonderworkers and charlatans to the confrontation of natural products and
      magical fluids with scientific knowledge. He considers the role of the
      pediatricians in finding a solution to the dialectics of his own death, for only
      by doing so will the pediatrician be able to competently and maturely handle the
      challenge represented by the death of his terminal patients. He finishes by
      drawing attention to the importance of psychological assistance to the terminal
      child and its family.

PMID- 14688915
TI  - [Lead poisoning: Zinc protoporphyrin in blood of children from Santo Amaro da
      Purificacao, Bahia, Brazil].
AB  - A cross-sectional epidemiological study has investigated lead poisoning among all
      the 101 children aged 1 to 5 years, living at less then 500 m from a lead smelter
      which has been operating since 1960 in Santo Amaro da Purificacao, State of
      Bahia, Brazil. Lead poisoning was evaluated by determining the concentrations of
      zinc protoporphyrin (ZPP) in whole blood. Results were compared with those
      obtained from 98 children of the same age range, in a nursery from Salvador,
      capital of the State of Bahia. In Santo Amaro, ZPP geometric mean was 65.5 mg/dl
      (geometric S.D. = 1.7), much higher, therefore, than the normal threshold of 30
      microg/dl recommended by the CDC-USA. A child was excluded from statistical
      analyses because of very high ZPP level: 789 mg/dl. In Salvador, ZPP geometric
      mean was 31.0 mg/dl (geometric SD = 1.6). "Extremely elevated" ZPP levels (above
      156 mg/dl) were observed in 8% of the children from Santo Amaro and in none (0%)
      of the children from Salvador, this statistical difference being highly
      significant. Anaemia was present among 35.0% of the children from Santo Amaro and
      among 25.5% of those from Salvador. One year-old children showed the highest
      levels of ZPP and anaemia. No marked statistical association was found between
      ZPP levels and anaemia. Lead contamination of this children population remained
      in a permanently high level during, at least, the period from 1980 to 1992. In
      December, 1993 the lead smelter has definitively ceased its industrial activities
      in Santo Amaro da Purificacao.

PMID- 14688916
TI  - [Mercury hazard in pediatric practice].
AB  - Medical doctors, nurses, attendants, and patients at the UFRJ paediatric hospital
      were accidentally exposed to inorganic mercury. From July to December 1992, 228
      mercury thermometers were broken in 6 paediatric wards. Contamination of the
      exposed group was assessed by a comparative cross sectional study in January 93.
      Mercury concentration was found to be two times higher in the urine of these
      professionals than in the control group (p<0.001).

PMID- 14688917
TI  - [Treatment of pediatric outpatients with complicated urinary tract infections].
AB  - In an open and prospective study involving outpatient children with complicated
      urinary tract infections (UTI), we evaluated the therapeutic efficacy of
      ceftriaxone administered intramuscularly, once-daily--50 to 70 mg/kg, during 8 to
      10 days. Initially, the selected patients exhibited at least two of the following
      clinical criteria: age below 6 months, any degree of toxicity, fever, strong
      suspicion or proved abnormalities of their urinary tracts and lumbar pain in
      children older than 4 years. Significant bacteriuria was demonstrated by urine
      culture in 40 patients (21 boys, 19 girls), whose ages ranged from 15 days to 6
      years 9 months (median 3 months). The radiological studies revealed
      vesicoureteral reflux in 6 patients, urethral posterior valve in 1, and
      neurogenic bladder in 4. The main causative agents were Escherichia coli isolated
      in 30 patients, Klebsiella (4) and Proteus (4). The treatment was found to be
      effective in 38 patients (95%). There was failure of treatment in 1 patient and a
      symptomatic reinfection in another one. It was concluded that children with
      complicated UTI could be treated alternatively by once daily ceftriaxone.

PMID- 14688918
TI  - [Comparison of seroconversion rates between well-nourished and malnourished
      children after measles immunization at nine months of age].
AB  - The study was based on activities developed at Embu, SP, between October 1989 and
      June 1990. Its purpose was to study serological turning after child vaccination
      against measles at the age of nine months. Two groups were compared, both within
      the same age limits. Group number I included eutrophic children and group number
      II included undernourished children. Gomes criteria was used to evaluate the
      childrens nutritional state. Antibodies (AB) dosage was done through
      hemagglutination inhibition (HI) and ELISA. These two laboratory methods were
      also checked regarding its sensibility. Out of 130 children studied, 80 could be
      evaluated. From this total, 56 (70%) belonged to group I and 24 (30%) belonged to
      group II. When the ELISA method was used, a significantly higher seroconversion
      percentage (P < 0.05 or 5%) was found among children belonging to group II. This
      percentage was not detected when the HI method was used.

PMID- 14688919
TI  - [Computerized ambulatory adolescent care--the experience of PAIA/ABEB].
AB  - PAIA (Program for Adolescent Integral Assistance from ABEB) is one of the
      preventive medicine programs of the Employee Beneficent Association at Belgo
      Mineira Metallurgy Company. Since its implementation, in February 1992, it has
      been offering specific medical assistance and educational instruction to
      adolescents from 11 to 18 years old through informative group dynamics. Age and
      maturity level are the guidelines for group formation. The groups are supervised
      by a multidisciplinary team and the methodology is playful and participatory. The
      themes approached in the meetings are chosen according to the adolescents'
      interest and maturity. After two years, the program was completely computerized
      aiming at improving the quality of assistance and accelerating services.
      PAIA/ABEB Program has surpassed all expectations concerning adolescents' and
      parents' interest and participation and the adolescents have become extra sources
      of information about the program and health education in their community.
      Behavioral changes like more concern about health care and more search for
      dialogue with meaningful adults have been observed. The observations and research
      carried out with adolescents have become a guideline for the preventive medicine
      campaigns at the firms belonging to Belgo Mineira Group. Indeed, differentiated
      medical assistance and global approach towards adolescence have been created in
      the clinic centers.

PMID- 14688920
TI  - [The importance of clinical examination for the diagnosis of innocent heart
      murmur in adolescents].
AB  - PURPOSE: To determine the prevalence of innocent murmur among adolescents, and to
      evaluate the clinical features in comparison with echocardiogram (two
      dimensional, M-mode, Doppler, and color-Doppler) in the assessment of heart
      murmurs. METHODS: The study was carried out from March to December, 1992, and
      involved high school students coming from families of the medium and low-medium
      social classes. Considering the total of 1400 students registered in a public
      school, 536 adolescents aging from 10 to 20 years were admitted in this study.
      Twenty seven students with heart murmur were submitted to Echocardiography in
      order to find any cardiac lesions. RESULTS: Among 536 adolescents, 171 (32%) had
      some kind of heart murmur. On the basis of the clinical diagnosis, 160 (29.9%)
      patients were classified as having innocent murmur and 11 (2.1%) as having
      "pathologic murmur". Out of 27 students submitted to echocardiography, 20 of them
      with clinical diagnosis of innocent murmur showed normal results. Among seven
      students with clinical diagnosis of "pathologic murmur", the echocardiography
      recognized cardiac lesions in two (small ventricular septal defect and rheumatic
      heart disease: combined mitral incompetence and stenosis, and aortic
      incompetence). CONCLUSION: From the data obtained, the prevalence of innocent
      murmur among adolescents was 29.9% on the basis of clinical diagnosis. It is
      suggested that careful clinical examination by physicians skilled in cardiac
      examination is the recommended method for the diagnosis of innocent murmur
      (sensitivity of 100% and specificity of 80%).

PMID- 14688921
TI  - [Prevention of anemia in the first year of life in health centers of Santo Andre,
      Sao Paulo].
AB  - The aim of this study was to evaluate the efficacy of an iron prophylactic
      supplementation program, in three health centers of Santo Andre, in Sao Paulo
      state. The prevalence of anemia was identified in a control group consisting of
      201 children of 1 year old. The intervention group consisted of 308 children
      younger than 3 months, but 55% of them gave up during the survey. The mothers
      were instructed to give them daily prophylactic doses of iron sulfate (6 mg of
      iron/day) when they were 4 or 6 months old, according to the kind of breast
      feeding. The mothers were also instructed about feeding and anemia and its risk
      to children's health. When the children were 12 months old, the diagnosis of
      anemia was made through dosage of hemoglobin concentration and the results were
      compared with those of the control group. It was verified that the 2 groups
      presented similar prevalences. It is important to realize that children with low
      frequency of visits to the health centers had prevalence of anemia significantly
      higher than those with high frequency. Some factors that possibly contributed to
      the result of the intervention are discussed.

PMID- 14688922
TI  - [Abdominal cystic lymphangioma in childhood: report of eight cases].
AB  - Lymphangioma is a common pathology in children, however intra-abdominal cystic
      lymphangioma is rare. Morphology and clinical symptoms are variable and can be
      mixed up with other etiology. Ultrasound can make the diagnosis in the majority
      of the cases. Surgery is the best choice of treatment and prognosis is in general
      good. Authors present eight cases in a period of fifteen years, all of them
      treated surgically. Results were good in seven cases. One late death was
      observed.

PMID- 14688923
TI  - [Kabuki make-up syndrome].
AB  - The authors present an original case, the first in Brazil and Latin America, of
      the Kabuki make-up syndrome. To diagnose KMS, the authors point out the
      importance of the "Pentad of Niikawa", a term created by them to indicate the
      five basic features of the syndrome. Also new symptoms and signs which might be
      part of the phenotype of KMS are described. The authors emphasize that studies
      concerning KMS be widely spread, in order to identify new cases.

PMID- 14688925
TI  - [Autologous bone marrow transplantation in pediatric oncology. A procedure for
      the future?].

PMID- 14688924
TI  - [Post-parotitis myocarditis: case report].
AB  - In November, 1993,M.G., a 6 year and 11 month-old girl, was admitted at Hospital
      Infantil Joana de Gusmao--Florianopolis, SC, Brazil--with post-parotitis
      myocarditis and congestive heart failure. Three days after admission it was
      evidenced, on an echocardiogram, a thrombus in the left ventricle apex which,
      despite of correct treatment, embolized to iliac and small mesenteric arteries.
      Epidemic parotitis (mumps) is very common, being endemic around the world.
      Complications are rare and myocarditis, one of them, is more common than
      diagnosed because of its poor and benign manifestations, generally transient
      abnormalities of cardiac rhythm and conduction. This case was astonishing because
      of its rare subsequent event, that is, the formation of a ventricular mural
      thrombus during an acute myocarditis.

PMID- 14688926
TI  - [Allergy skin testing after topical anesthesia].

PMID- 14688927
TI  - [Islet cell autoantibodies and development of diabetes in relatives of patients
      with insulin-dependent diabetes mellitus].

PMID- 14688928
TI  - [Occupational risks in childhood and adolescence: a review].
AB  - The authors present a brief bibliographic review of the health risks to which
      children and youth are often exposed in the workplace. The concern regarding
      these risk factors is justified based on the fact that children and youth
      comprise a large portion of the work force and begin working at early ages. At
      the same time these children and youth are undergoing profound biological,
      psychological and social changes and therefore are susceptible to occupational
      illnesses. With this in mind, the article seeks to alert health professionals
      regarding possible occupational health risks to children and youth in the
      workplace.

PMID- 14688929
TI  - [Autologous bone marrow transplantation in pediatric oncology--preliminary
      results from the ICR].
AB  - The initial results of 19 autologous and 1 syngeneic bone marrow
      transplantations, done in children with neuroblastomas (14), non-Hodgkin's
      lymphomas (3), Ewing sarcoma (1), acute lymphocytic (1) and non-lymphocytic (1)
      leukemias, pioneerely started in Brazil in February, 1987, and specially after
      the beginning of the ICR Marrow Transplantation Program, in October, 1989, are
      here described. Methodology, toxicity and survival are discussed. The efforts for
      establishing a high technology program in a public and universitarian
      institution, deeply supported by the community, are emphasized. Future directions
      are also discussed.

PMID- 14688930
TI  - [Allergy skin testing after topical anesthesia].
AB  - Immediate skin test reactions are the hallmark of atopic diseases. EMLA (eutectic
      mixture of local anesthetics) is a local anesthetic that reduces the pain and
      apprehension for skin testing. We studied EMLA effects on the skin prick test
      with allergen and histamine. Reactions were evaluated by means of wheal and flare
      crossed diameters, speed of reaction and local temperature changes. One hour
      occlusion dressing with EMLA significantly delayed the beginning of reaction with
      antigen (129%) and histamine (101%). It decreased wheal diameter (33% and 15%) as
      well as local temperature variation (55% and 80%) respectively with antigen and
      histamine. Local anesthesia with EMLA probably interferes with histamine action
      and reduces the immediate skin test reaction. Therefore, it should not be used to
      reduce the pain of allergy skin testing.

PMID- 14688931
TI  - [Progression to IDDM and islet cell antibodies (ICA; ICA-CF)].
AB  - We have followed eight first-degree relatives of IDDM patients (insulin
      dependent, type I diabetes) attending the outpatient diabetes clinic at the State
      University of Rio de Janeiro for three years, all of them with positive islet
      cell antibodies (ICA and/or ICA-CF). Three out of eight relatives less than
      fifteen years old have subsequently progressed to overt Insulin-Dependent
      Diabetes Mellitus (IDDM) 12, 21 and 8 months after the first positive
      autoantibodies detection. Four relatives have remained with ICA and/or ICA-CF
      positive, and in another one the reaction became negative during the observation
      period. A positive correlation has been found between high titles of ICA (> or =
      1/16) and development of IDDM. We have concluded from our prospective study
      during three years that of our antibody-positive relatives, 37.5 % have developed
      overt diabetes, all of them being less than fifteen years old, with high titles
      of ICA and ICA-CF positive.

PMID- 14688932
TI  - [Monitorization of blood levels of vancomycin in children with multi-resistant
      bacterial infections].
AB  - Pharmacokinetics of vancomycin depends on many factors and one of them is the age
      of the patient. It is better known in adults and there are few studies in
      children. Therefore, we studied the serum concentrations in 22 children with
      multi-resistant bacteria infections that received vancomycin. The doses
      administered followed the recommended rules for its utilization. This study was
      made at the equilibrium phase and immunofluorescence was the method utilized. The
      peak serum concentrations varied from 23 to 99 mcg/ml and only in 8 children
      (36%) they varied from 30 to 40 mcg/ml. In 10 cases (45%) we found valley serum
      concentration between 5 to 10 mcg/ml. These observations confirm the
      imprevisibility of serum concentrations obtained from one single recommended
      dose. Therefore, due to the complexity of vancomycin pharmacokinetics, the
      monitoring of blood levels is recommended in order to obtain therapeutic success.

PMID- 14688933
TI  - [Septicaemia caused by Klebsiella pneumoniae--a review of 28 cases].
AB  - Twenty-eight children with septicaemia and positive blood cultures for Klebsiella
      pneumoniae were retrospectively studied and compared with 190 children with
      sepsis caused by other organisms, identified or not in blood cultures.
      Septicaemia due to Klebsiella pneumoniae occurred more frequently in children
      older than 2 years of age, especially those who had an underlying disease and,
      therefore, were malnourished or had an impaired immune defense system that had
      required invasive procedures and previous hospitalization. Although the case
      fatality rate was high in both groups, Klebsiella pneumoniae did not contribute
      to elevate the relative risk of death. In this study, Klebsiella pneumoniae
      isolates were highly sensitive to colistin (92.9%) and cefoxitin (82.1%), but
      poorly sensitive to third generation cephalosporin and imipenen.

PMID- 14688934
TI  - [Anthropometric evolution during hospitalization of severe malnourished children
      with persistent diarrhea receiving standardized nutritional support].
AB  - In order to estimate the nutritional rehabilitation (NR) during admission of
      malnourished children with persistent diarrhea (PD) receiving standardized
      nutritional support (NS), we prospectively evaluated the weight, height, head
      circumference and arm measurements (AM) of 20 children, 19 below 1 year, admitted
      to the ward with weigh/age -2.89 to -5.21 standard deviation. Four infants
      comprised the death group (DG) and 16 survived (SG). The SG was separated,
      according to initial weight behavior, into weight gain (WG) or weight loss (WL).
      Compared to SG at admission, DG only had lower AM and more metabolic-infectious
      alterations (p<05). The survivors presented NR but this was evident for WL only
      when considering the minimum weight. DG received less calories than SG and weight
      loss during the pre-death period was higher than for WL (p<05). It was concluded
      that very altered AM, severe metabolic-infectious insults, low caloric input and
      high weight loss velocity are associated to bad prognosis; severely malnourished
      infants with PD began NR during hospitalization while receiving adequate NS, but
      minimum weight must be considered for this evaluation; AM must be obtained at
      admission, due to its prognostic value, and adequate NS as well as anthropometric
      follow-up during the hospital stay are essential.

PMID- 14688935
TI  - [Congenital rubella syndrome and the occurrence of congenital heart disease].
AB  - Aiming to document the incidence and type of associated congenital heart disease,
      20 children affected with the congenital rubella syndrome have been evaluated
      during a 5 year period, starting 1988. Congenital heart disease was detected in
      45% of the cases. Persistent ductus arteriosus was the most frequent finding,
      followed by ventricular and atrial septal defects. Hearing disturbances occurred
      in 83% of the 12 cases studied. Ophthalmic lesions appeared in 69% of the 13
      cases analysed, congenital cataracts being the most frequent one. An association
      of 66% was found between ophthalmic and heart lesions. Regarding the nutritional
      index, 70% of the cases were situated between the 25th and 50th percentile. The
      relevant incidence of congenital defects and the documentation of an important
      number of cases in a short period of time point out to a significant prevalence
      of the syndrome with imperative need improve the vaccination programs.

PMID- 14688936
TI  - [Growth analysis of 566 children from the fourteen day care centers of Paulinia
      (Sao Paulo, Brazil), with ages ranging from 3 months to 3 years].
AB  - To study the growth of 566 children (273 males and 293 females) from fourteen day
      care centers of Paulinia (Sao Paulo, Brazil), with ages ranging from 3 months to
      3 years, admitted from March 1st to May 31st, 1993, the authors analyzed the z
      score distribution of height for age and weight for height in relation to age
      group, per capita family income, social class levels, mothers education level and
      child birth weight. The Kruskal-Wallis test and the Multiple Comparison test were
      used in the statistical analysis. The children with less than 24 months or with
      birth weight less than 3000 g as the children with mothers education level less
      than four years, presented left deviated distribution in the height for age z
      score. The weight for height score was less satisfactory in the group with per
      capita income less than one salary, in the group with birth weight less than 3000
      g, and in the group with ages superior to 18 months.Therefore, institutional
      actions concerning the children and their parents are recommended in order to
      attenuate these factors.

PMID- 14688937
TI  - [Ultrasonographic diagnosis of hidrohematometrocolpos: case report].
AB  - After reviewing the literature, the authors report a case and the
      ultrasonographic findings of hidrohematometrocolpos. They also report the
      differential diagnoses and the diagnostic criteria.

PMID- 14688938
TI  - [Tubular duplication of the colon: a case report and review of the literature].
AB  - Among Gastrointestinal Duplications, colonic duplications are the less common.
      The case presented here consist of a duplication of the transverse colon,
      difficult to diagnose, which had abdominal distension as the main symptom. A 4
      year-old child was referred to the Unity of Pediatric Surgery, Hospital de Base,
      Brasilia, DF with a history of progressive abdominal distension. Plain X-Rays of
      the abdomen demonstrated a large fecaloma, which demanded removal. A Barium Enema
      was done suggesting Congenital Megacolon. A rectal biopsy was performed under
      general anesthesia, demonstrating normal ganglion cells. Medical treatment was
      instituted for chronic constipation in the Pediatric Gastroenterology clinic. The
      patient returned three months later with the same complaints. A new rectal biopsy
      was done; normal ganglion cells were described, ruling out Hirschsprung's
      disease. The parents were told to insist on the medical treatment diets. Four
      years later the patient was seen in the Emergency Room with signs and symptoms of
      low intestinal obstruction. Exploratory Laparotomy was undertaken as an emergency
      and the findings were complete volvulus of the large bowel involving the
      transverse colon up to the splenic flexure, demonstrating a large duplication of
      the transverse colon. A resection of the duplication and end-to-end colonic
      anastomosis was performed with an uneventful postoperative care. Discharged on
      excellent conditions.

PMID- 14688939
TI  - [Septic sacroiliitis: case report].
AB  - Bacterial pyogenic sacroiliitis is a relatively rare infection that may be
      difficult to diagnose. A delay in the diagnosis may be associated with marked
      toxemia and demanded surgical drainage of the septic joint. We report clinical
      and laboratorial findings in a 12-year-old white girl with onset low back and leg
      pain two weeks before admission to the hospital. Bone scintigraphy showed
      increased uptake in the right sacroiliac joint and radiologic changes were
      typical of sacroiliitis. Oxacilin-sensitive S. aureus was cultured from fluid of
      surgical biopsy. Antibiotic treatment leads to complete recovery after long time
      with low back pain. The diagnosis and treatment of this rare disease are
      discussed based upon our finding and the literature data.

PMID- 14688940
TI  - [Psoas muscular abscess in children].
AB  - Symptoms of psoas muscular abscess in children are nonspecific and differential
      diagnosis is made among diseases included in childrens acute hip pain syndrome,
      imaging tests being necessary for diagnostic confirmation. During the first
      semester of 1995, 48,550 children were examined in Pronto Socorro do Instituto da
      Crianca do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao
      Paulo, four of them diagnosed as having psoas muscular abscess (2 females and 2
      males, ages varying from 1 to 12 years). All of them had nonspecific clinical
      features and diagnosis was confirmed by abdominal ultrasound and/or computerized
      tomography. Staphylococcus aureus was isolated as the etiologic agent in 3
      children, findings similar to the ones in literature.

PMID- 14688942
TI  - [Apgar score and fetal acidemia].

PMID- 14688941
TI  - [Nitric oxide in persistent pulmonary hypertension of the newborn].

PMID- 14688943
TI  - [Congenital ChagasDisease: epidemiology, laboratorial diagnosis, prognosis and
      treatment].
AB  - The authors review studies about epidemiology, clinical aspects and methods used
      in laboratorial diagnosis of congenital Chagas'disease, emphasizing the
      limitations in their specificity and sensibility, and suggest alternative methods
      to improve the accuracy and the quality of the laboratorial diagnosis of
      congenital Chagasdisease, essential to an efficient treatment.

PMID- 14688944
TI  - [Nitric oxide in the treatment of neonatal pulmonary hypertension].
AB  - This study describes the effects of nitric oxide in newborns with persistent
      pulmonary hypertension. We studied 9 infants with severe respiratory failure
      characterized by hypoxemia and pulmonary hypertension. All infants met ECMO
      criteria and the oxygenation index (OI) was greater than 25. Mean birth weight
      was 2698 -/+ 661 g and gestational age was 36.4 -/+ 2.6 weeks. Nitric oxide was
      administered in a Y circuit in the inspiratory line of the mechanical ventilator.
      Nitric oxide and NO2 concentrations were monitored with electrochemical analyzers
      (PACI and PACII-Draeger). Pulmonary hypertension was diagnosed with clinical and
      echocardiografic criteria, with detection of right to left shunt with color
      doppler. All patients showed a dramatic improvement in oxigenation after nitric
      oxide administration. The drug reduced the mean OI, which was 48.5 before its
      administration, to 17.7 after 30', 14.1 after 6 hours, and 10.5 after 12 hours.
      We observed in all patients a reduction in pulmonary vascular resistance,
      reversal of the right to left shunt without any effects on systemic arterial
      pressure. Metahemoglobin levels did not reach 1.5% in any patient. Only one out
      of the 9 patients died, after reversal of the pulmonary hypertension, from other
      complications of perinatal asphyxia. Our data show that nitric oxide is a
      promising drug in the treatment of neonatal pulmonary hypertension and that it
      may reduce the need of ECMO in severe respiratory failure.

PMID- 14688946
TI  - [Hyperkalemia in very low birthweight infants: incidence and associated factors].
AB  - The present study evaluated the incidence of hyperkalemia in premature babies
      born at the Hospital de Clinicas de Porto Alegre (birthweight <or= 1250 grams and
      gestational age <or= 32 weeks) during the first 72 hours of life in a one year
      period. The incidence of hyperkalemia was of 38.5% (potassium levels >or=6 mEq/l)
      and 15.4% with potassium levels subject to cardiac arrhythmia (>or= 6.7 mEq/l).
      The population was divided into two groups: group KN with potassium < 6 mEq/l
      (n=16) and group KE with potassium >or= 6 mEq/l (n=10). The hydroelectrolyte
      management and maintenance of neutral thermal environment was the same for both
      groups. Neither group received potassium in the first 36 hours of life. The KE
      group presented higher potassium levels during all the study. The mean
      birthweights of the groups were similar (KN = 963 gr; KE = 987 gr). The KN group
      presented a mean gestational age (29.3 weeks x 30.8 weeks) and Apgar Score in the
      first minute of life (3.18 x 5.7) significantly lower (p = 0.004 and p = 0,015
      respectively) than the KE group. There were no significant differences between
      both groups in relation to the intraventricular hemorrhage, acidosis, hialine
      membrane disease, insulin level, glycemia, glycemia/insulin index, glomerular
      filtration rate, diurese, urinary potassium level, fractional sodium excretion,
      fractional potassium excretion and aldosterone tubular index. The level of
      aldosterone was significantly higher in the KE group (p = 0.029) within 24 hours
      of life (212.8 ng/dl x 110.2 ng/dl). It is suggested that none of the studied
      factors is responsible for the non-oliguric hyperkalemia of the very low
      birthweight newborn infant, stressing, however, that the serum potassium level
      must be carefully controlled in those infants.

PMID- 14688945
TI  - [Evaluation of umbilical cord pH and its relationship with Apgar score in term
      newborn infants].
AB  - The value of the Apgar score as an index of birth asphyxia has been recently
      questioned. The purpose of the present study is to evaluate the relationship
      between cord blood pH and Apgar score in term newborn infants.A cross-sectional
      study involving 76 term newborn infants was performed from March through
      September 1995 at the Obstetric Unit of Hospital de Clinicas de Porto Alegre. The
      blood samples were obtained from umbilical cord artery and vein at the moment of
      delivery. Infants were divided in three different groups according to the Apgar
      score: Group A (n=60): >or=7 at one and five minutes; Group B (n=13): < 7 at one
      minute and >or=7 at five minutes; Group C (n=3): < 7 at one and five minutes. The
      frequency of acidemia in Group A was 18.3% (11 newborn infants) considering
      arterial pH < 7.20 and 5% considering arterial pH <or= 7.10. Three newborn
      infants (23%) of Group B had arterial pH >or= 7.20 and nine (56.2%) had arterial
      pH > 7.10. None of the newborn infants in Group C had arterial pH > 7.10. The
      sensitivity and specificity values for Apgar score less than 7 at one minute for
      detection of fetal acidemia were, respectively, 54.1% and 94.1%. This study
      confirms a poor correlation between Apgar score and umbilical blood cord pH, even
      in a term newborn, and emphasizes the importance of obtaining umbilical cord pH
      to consider the diagnosis of perinatal asphyxia.

PMID- 14688947
TI  - [Single x double phototherapy for the treatment of hyperbilirubinemia in high
      risk newborn infants].
AB  - This is a randomized, prospective, controlled study to compare the efficacy of
      single versus double halogen phototherapy in high risk patients admitted to a
      newborn intensive care unit. Eighty patients were allocated to receive single
      (N=43) or double (N=37) phototherapy. The groups were similar in clinical and
      laboratory characteristics. Total serum bilirubin (SB), hematocrit and total
      serum protein were assessed by microanalysis prior to the beginning of the study
      and at 6, 12, 18 and 24 hours of treatment. The percent decline of SB was
      significantly higher in the double phototherapy group. This difference is first
      noted at 12h of treatment (10% vs 1.8%, p< 0.01) and is acentuated at the end of
      the study (19.4% vs 1.6%, p< 0.0001). Weight loss, variations in the hematocrit
      and total serum protein were similar in both groups. Cutaneous rash and
      temperature instability were not noted among the patients studied.Our results
      demonstrate that double phototherapy is more efficient than single phototherapy
      in treating hyperbilirubinemia in high risk newborn infants.

PMID- 14688948
TI  - [Evolution of systemic arterial blood pressure during neonatal period in term
      newborns adequate for gestacional age].
AB  - The authors studied the levels and evolution of systolic, mean and diastolic
      arterial blood pressure in term newborns adequate for gestacional age during the
      first month of life. The applied technique was oscillometric, using a non
      invasive monitor. The study was prospective, including newborns who had received
      first minute Apgar score above 6, with no clinical disturbances or use of any
      drug with possible arterial blood pressure side effects. The measurements of
      systolic, mean and diastolic arterial blood pressure were taken at 12 hours of
      life and 3rd, 7th, 14th and 28th days of life. The authors observed an increase
      in arterial blood pressure mean values from the 1st to the 7th day of life and
      that there was no significant changes on the same measurements from the 1st to
      the 4th week of life.

PMID- 14688949
TI  - [Neonatal cholestasis and cytomegalovirus infection: clinical and histopathologic
      forms].
AB  - Cytomegalovirus infection is symptomatic in only 10% of cases. The most frequent
      findings are cholestasis and hepatosplenomegaly. Ten patients who presented
      neonatal cholestasis associated with cytomegalovirus infection were studied. The
      majority had elevation of serum aminotransferases and mild abnormality of hepatic
      function. The histopathologic findings were: normal, giant cell hepatitis, bile
      duct proliferation (confused with extrahepatic biliary atresia) and ductopenia.
      The clinical course of the patients varied from disappearance of the symptoms (2
      cases) to death (2 cases). Because of the possibility of confusing the histologic
      findings with extrahepatic biliary atresia, the etiology of neonatal cholestasis,
      including cytomegalovirus infection, should be determined as soon as possible.

PMID- 14688950
TI  - [Growth of premature infants fed own mother's milk supplied with two milk
      formulas].
AB  - The purpose of the authors in this article was to evaluate the effects of
      supplementing maternal milk with two different caloric formulas on the growth of
      premature newborns until they reached 40 weeks of post-conceptional age. Seventy
      premature infants weighing < 1750g at birth were randomized: 35 adequate for
      gestational age (AGA) and 35 small for gestational age received maternal milk and
      either a special preterm formula or a modified formula. Anthropometric
      measurements and clinical evaluations were used to determine the nutritional
      status and the postnatal growth of these infants, who were analyzed in six
      different moments: at maximum weight loss, at return to birth weight, at definite
      weight gain, when exclusively fed with formula, at 2000g, and when they reached
      40 weeks of post-conceptional age. The AGA premature newborns on preterm formula
      had greater daily weight gain, cephalic circumference increase and growth. The
      SGA premature newborns on preterm formula had greater daily weight gain and
      cephalic circumference increase observed from the third week of life onward. The
      AGA premature newborns on modified formula had less weight gain and smaller
      increments in the cephalic circumference. The SGA premature on modified formula
      had the worst anthropometric results. The preterm formula was more efficient than
      the modified formula in promoting postnatal growth of AGA and SGA premature
      infants. We believe that, due to their special characteristics, SGA premature
      should receive individualized nutritional caloric planning

PMID- 14688951
TI  - [Babkin's reflex in newborn: new reflexogenous zone].
AB  - The authors have studied the hand-mouth reflex of Babkin on 422 newborns. 413 out
      of 422 newborns were considered normal. We have found responses not yet published
      such as accentuation of inferior limb flexion, trunk flexion, upper limb
      adduction, contraction of the mentalis muscle, contraction of the orbicular of
      the lips, extension of the inferior limb, extension of the pododactiles and cry.
      We obtained the same responses by pressing the infraclavicular space just near
      the esternal bone. We compared statistically: a) responses to the stimulus on the
      palm of the hand and on the new reflexogenous zone; b) responses presented by
      term and preterm newborns; c) responses of newborns less than 12 hours of age and
      more than 24 hours of age.

PMID- 14688952
TI  - [Rectal atresia].
AB  - The authors report a case of rectal atresia by diaphragm in a newborn four days
      old, male, with colon obstruction. Diagnosis was made by clinical
      characteristics, physical examination and radiographic features. After
      compensation of hydro-electrolytic disturbances, the patient was submitted to
      surgical treatment. Discharged one week from operation.

PMID- 14688954
TI  - [Striving for the improvement of the nutritional status of our children and
      adolescents: we shall not abandon our position!].

PMID- 14688953
TI  - [Harlequin fetus].
AB  - The authors show a typical case of harlequin fetus. After a description of the
      gross features found in a male newborn, several aspects concerning genetics,
      physiopathology, diagnosis, treatment and prognosis are discussed.

PMID- 14688955
TI  - [Symptoms and signs in acute otitis media].

PMID- 14688956
TI  - [Inborn errors of metabolism: practical guidelines for clinical diagnosis in
      acutely ill children and infants].
AB  - The manifestations of Inborn Errors of Metabolism (IEM) with an acute
      presentation are extremely unspecific, which makes its diagnosis a task of
      laboratorial interpretation. At the same time, the early diagnosis of many of
      these IEM allows quite satisfactory therapeutic interventions, followed by
      favorable clinical evolutions. To make the work of pediatricians and
      neonatologists easier in the diagnosis and immediate management of these
      conditions with an acute onset, a flowchart of procedures is suggested. The
      different steps suggested are justified and complemented by adjacent comments,
      which are restricted to the more serious and common manifestations of these
      disorders, like metabolic acidosis, hyperammonemia and hypoglycemia. Finally, the
      reading of specific and more detailed literature is suggested for the
      understanding of the different families of specific IEM.

PMID- 14688957
TI  - [Evaluation of the Malnourished Children's Recuperation Program in the town of
      Embu, located in the Metropolitan Area of Sao Paulo].
AB  - The objective of this study is to assess the anthropometric evolution of children
      who had been assisted by the Malnourished Children's Recuperation Program in the
      town of Embu, as well as to analyze some variables that interfered in this
      evaluation. The study included 233 children aged under five, enrolled in the
      program from January 1984 to December 1985. 201 (86,3%) were undernourished grade
      II and 32 (13,7%) grade III, according to Gomez. The percentage increase of
      Weight in relation to Age (W/A) and Height in relation to Age (H/A) - outcome
      variables, in the first and last examinations in the program - were analyzed,
      using the multiple linear regression. Younger children and in worse nutritional
      conditions showed higher W/A and H/A increases. Low birth weight, more frequent
      examinations, and longer stay in the program were associated to lower W/A
      increases. The presence of chronical pathologies jeopardized the H/A rate
      increases. This result strengthens the importance of developing programs for the
      assistance of undernourished children, due to higher risk of morbi-mortality in
      this group, mainly in younger children and with worse nutritional conditions.

PMID- 14688959
TI  - [Relations among arm, arm muscle, arm fat areas and menarche in adolescents in
      the municipality of Botucatu].
AB  - The authors show the relations among arm circumference, arm muscle and arm fat
      areas with or without menarche, by carrying out an anthropometric study in 717
      adolescents in the municipality of Botucatu. It must be emphasized that those
      adolescents who had already menstruated presented significantly higher
      nutritional indicators than those who had not menstruated yet. There was an
      increase in fat tissue and lean body mass in those adolescents who had already
      menstruated. Body changes might be expressed by calculating muscle and arm fat
      areas using triceps skinfold and arm circumference.

PMID- 14688958
TI  - [Assessment of the nutritional status of Brazilian adolescents by body mass
      index].
AB  - The assessment of nutritional status of adolescents is not an easy task because
      it should take into account sex, age, weight, stature and sexual maturation of
      the adolescents. In addition, an adequate classification should also be related
      to subsequent health-related outcomes during adult life. On the other side,
      screening for overweight and underweight among adolescents is highly desirable
      since nutritional status during adolescence correlates with adult body habitus.
      The objective of this study was to propose a classification for screening the
      nutritional status of Brazilian adolescents based on the body mass index
      (kg/m(2)) provided by the Pesquisa Nacional sobre Saude e Nutricao-PNSN, a
      national survey of the Brazilian population carried out on 1989. We defined as
      cutoff the 10th and 90th percentile of the body mass index distribution and the
      10th percentile for stature.

PMID- 14688960
TI  - [Evaluation of the diagnostic power of symptoms and signs in acute otitis media].
AB  - The diagnosis of acute otitis media (AOM) is made on clinical basis. The gold
      standard tests are invasive. There are few studies quantifying the diagnostic
      power of the signs and symptoms. A sample of 300 children were analyzed to
      establish the diagnostic power of isolated and combinated signs and symptoms in
      AOM. The most important diagnostic signs were bulging, fluid level, acute
      perforation, and change in color of the tympanic membrane. Fever was the single
      symptom with statistical significance. We concluded that we can do an accurate
      and noninvasive AOM diagnosis using otomicroscopic findings.

PMID- 14688961
TI  - [Lupic nephropathy in childhood: morphologic analysis of 18 cases].
AB  - Serum IgE concentration was determined in 17 newborn and 171 children with ages
      between 1 and 12 months. In the first group, blood was taken from the umbilical
      cord, and in the second, we used a periferic blood sample. The selection implied
      the exclusion of children with any suspicion of atopic disease, family history of
      atopy and recent viral infection. The serum IgE concentration was determined by
      enzyme linked immunoabsorbent assay (PRIST). The sex, race ( white and non white)
      and age were analyzed in the children studied. During a follow-up period (24
      months) seven children (3,7%) developed atopic symptoms. The serum IgE
      concentration of the groups studied was higher than in other studies. The mean
      IgE in each group was as follows : newborns = 0.24 IU/ml; 1-3 months = 1.57
      IU/ml; 4-6 months = 7.72 IU/ml; 7-9 months 12.07 IU/ml; 10-12 months = 12.14
      IU/ml.

PMID- 14688962
TI  - [Congenital Malaria. Case reports and a brief review of literature].
AB  - Two cases of congenital malaria due to Plasmodium vivax and Plasmodium falciparum
      respectively are reported. The children were born in Sao Paulo and Parana to
      mothers from endemic area of malaria. The mothers had malaria during pregnancy.
      The children were admitted with severe anemia and hepatosplenomegaly. Despite
      congenital malaria is being considered a rare event it is a preventable disease
      and these cases should draw attention to the importance of adequate treatment
      during pregnancy. Clinical manifestations and management of congenital malaria
      are also discussed.

PMID- 14688963
TI  - [Medullary sponge kidney, nephrolithiasis, hypercalciuria and hyperuricosuria in
      a child. Report of a case and follow-up].
AB  - The medullary sponge kidney is rare in children and may present it self with
      hematuria and nephrolithiasis. We report a case of medullary sponge kidney in a
      child with nephrolithiasis, hypercalciuria, hyperuricosuria and prolonged
      treatment which avoided the recurrence of nephrolithiasis.

PMID- 14688964
TI  - [Megacystis-microcolon-intestinal hypoperistalsis syndrome. A case report].
AB  - A case of intestinal pseudo-obstruction in the neonatal period is presented. It
      is known as Megacistis-microcolon-intestinal Hypoperistalsis Syndrome and is a
      rare cause of intestinal dismotility.A white female newborn weighing 3,110 g was
      admitted to the Neonatal Surgical Unit of the Hospital de Base with a small
      omphalocele and a history of biliary vomit. Abdominal X-rays revealed complete
      absence of intestinal gas. Exploratory laparotomy was carried out, and the
      findings were great distension of the bladder, a short poorly developed and
      malrotated bowel with a non-fixed cecum. Surgical treatment consisted of
      gastrostomy, sigmoid colostomy, vesicostomy and repair of the omphalocele.
      Multiple biopsies were done in the small and large bowel. Ganglion cells were
      present in all specimens. The patient did not tolerate enteral feeding, and total
      parenteral nutrition was readily initiated. Nonetheless, death occurred on the
      51st postoperative day. This is a rare syndrome which presents itself at birth as
      chronic intestinal obstruction. A postmortem examination confirmed the diagnosis.

PMID- 14688965
TI  - [Biliary atresia - evolution in the last two decades].

PMID- 14688966
TI  - [Missed opportunities for immunization].

PMID- 14688967
TI  - [Biliary atresia - study of 19 patients].
AB  - This is a retrospective analysis of 19 babies born with biliary atresia (12
      girls, 7 boys) who were treated at the Hospital das Clinicas of the Ribeirao
      Preto Medicine School. The portoenterostomy operation was performed in 16
      patients. All operations were performed before 12 weeks of postnatal life.
      Diagnostic laboratory studies are discussed. The authors conclude that the
      cholestatic jaundice protocol employed proved to be very necessary, can lead to
      early diagnosis can improve survival.

PMID- 14688968
TI  - [Missed opportunities for immunization in a pediatric hospital in Fortaleza,
      State of Ceara - Brazil].
AB  - To define missed opportunities for immunization (MOI) at Albert Sabin Children's
      Hospital, in the city of Fortaleza, Brazil, the author studied 119 outpatients
      aged under 24 months that were attended at the hospital. Thirty-seven children
      (31%) were missing vaccines. Ninety percent of the children had immunization
      cards but only 40% had their cards verified by health workers.Fifty-eight percent
      out of 43 inpatients were missing vaccines without contraindication and 54% of
      the mothers were missing doses of tetanus toxoid vaccine.Eighty-six percent of 22
      health workers had good knowledge about the vaccination schedule, but only 23%
      did know 3 true contraindications to vaccines. The most important causes of MOI
      were health workers' neglect to ask for the vaccination card and false
      contraindications.

PMID- 14688969
TI  - [Duration of bronchodilator effect of inhaled Salmeterol (dry powder x metered
      dose inhaler) in children with acute asthma attack].
AB  - Patients during a mild to moderate acute attack of asthma (FEV1: 50 - 80% of
      predicted) were treated with Salmeterol MDI - 50mcg or Rotadisk - 50mcg or
      Salbutamol (MDI -200mcg). The children were followed by Spirometry, measuring
      FEV1 (basal) and after treatment: at 30 minutes, 60 minutes and thereafter every
      60 minutes until 780 minutes, if the patients maintained the FEV1 above 80% of
      the predicted value and/or an increment of 20% in the VEF1 basal value. The
      Salmeterol group showed a significant bronchodilation at 60 minutes which was
      maintained in half of the patients up to 9 hours. This was not observed in the
      Salbutamol group: the peak bronchodilatation was observed at 30 minutes and the
      bronchodilation effect was observed in half of the patients up to 6 hours. There
      were no significant differences between both presentations of Salmeterol. This
      drug allowed a prolonged bronchodilator effect and is, according to the several
      consensus on management of asthma, an adequate option in the treatment of
      moderate to severe asthma.

PMID- 14688970
TI  - [Autonomic dysfunction in Guillain-Barre Syndrome: a 13 year experience in
      pediatric intensive care unit].
AB  - The acute inflammatory demyelinating polyneuropathy (Guillain-Barre Syndrome)
      might have a severe presentation but a good prognosis in children. It is an
      immune-mediated and inflammatory disorder of the peripheral nervous system. This
      retrospective study observed that GBS is frequently complicated by hypertension
      and other autonomic disorders. Cardiovascular instability is due to the
      involvement of the autonomic nervous system and results in labile blood pressure,
      cardiac dysrhythmias and hypovolemia. During a 13-year period (1982-1995), 21
      children were admitted to the Pediatric Intensive Care Unit of Sao Lucas
      Hospital, Porto Alegre, south of Brazil. Eight patients were mechanically
      ventilated. Symptoms of autonomic disturbance were frequently seen, especially in
      patients with severe clinical evolution. Previous investigations of the mechanism
      of hypertension associated with GBS did not evaluate the etiology of these
      phenomena. With modern pediatric intensive care support the deaths are rare.
      There is no death in this studied group.

PMID- 14688971
TI  - [Prescription of herbal teas for children under six months of age: the opinion of
      physicians from a middle size city in Southern Brazil].
AB  - A cross sectional study survey was carried out among physicians who work at
      children's clinics in Pelotas. The doctors were interviewed by medical students
      about the prescription of tea for children under six months, risk factors and
      breastfeeding. About half of the interviewed physicians prescribed tea. The main
      reasons for that were: intestinal colic (35%), diet supplementation (21%), and
      oral rehydration (18%). The relationship between tea and diarrhoea, tea and
      malnutrition, tea and weanning was acknowledged by 19%, 47% and 83% of them,
      respectively. These association remained significant (p<0.05) even after
      adjustments were allowed for graduation time and pos-graduation courses. The
      conclusion is that some common aspects of children's diet are not well managed by
      most of these doctors.

PMID- 14688972
TI  - [Lupic nephropathy in childhood: morphologic analysis of 18 cases].
AB  - The present study describes 21 cases (17 females and 01 male) of 12 year old
      patients, or younger, with diagnosis of SLE, that were submitted to renal biopsy.
      The histologic study demonstrated 10 cases of membranoproliferative
      glomerulonephritis (Class IV-WHO); 4 cases of focal proliferative
      glomerulonephritis (Class III-WHO; 2 cases of mesangial proliferative
      glomerulonephritis (Class II-WHO) and 2 cases of membranous glomerulonephritis
      (Class V-WHO). Three cases were excluded. In this study the incidence of lupus
      nephritis in children was small, similar to what has been described by other
      authors, and presenting unfavorable histologic patterns.

PMID- 14688973
TI  - [Munchausen's syndrome by proxy: a case report of a girl with a recurrent
      factitious bleeding ear].
AB  - This is a case report of a three-year-old girl with recurrent ear bleeding which
      was actually recurrent factitious symptomatology, perpetrated by the mother,
      which caused the child to undergo many harmful diagnostic procedures. This is a
      documented case, probably the first case reported in Latin America, and it is
      also the only one in which there is mention of the mother demonstrating interest
      in divulging the case. Munchausen's Syndrome by Proxy (MSBP) is a specific
      modality of child abuse. The mother, often the perpretator, affect concern and
      affection. The consequences are both psychological and physical and can determine
      child's death. Diagnosis is rarely considered.

PMID- 14688974
TI  - [Arterial hypertension due to mercury intoxication with clinical and laboratorial
      syndrome simulating pheochromocytoma].
AB  - A 17-year-old boy was admitted to hospital because of severe hypertension
      (200/130 mmHg), headache, irritability, sweating, etc. Initial biochemical tests
      suggested pheochromocytoma, being treated with nifedipina, clonidina and
      propranolol. On reporting exposure to mercury vapour, he underwent twenty-four
      hour urine screening and measurement of blood mercury which confirmed
      intoxication. The patient received courses of chelation therapy with dimercaprol
      (BAL) and penicillamine with remission of symptoms and normalisation of
      hypertension after 2 months. This case is relevant to current practice regarding
      similarity between mercury intoxication and hypertension secondary to
      pheochromocytoma.

PMID- 14688975
TI  - [Renal vein thrombosis in newborn infants].
AB  - The authors reviewed renal venous thrombosis (RVT), a frequent cause of acute
      renal failure in newborns. Clinical manifestations and prognosis are unsteady
      and, although there is agreement about the management of underlying conditions
      and general abnormalities, the relative role of anticoagulant and fibrinolytic
      therapy has not been clearly established. The 5 RVT described cases were treated
      in our hospital in the last 5 years. Four out of five were followed and one of
      these was submitted to nefrectomy to control arterial hypertension. The findings
      are compared to literature and present therapy is discussed.

PMID- 14688977
TI  - [Violence in childhood and adolescence].

PMID- 14688978
TI  - [Genetic deafness: a brief review].
AB  - In this article, we present a brief literature review of hereditary deafness,
      considering the main historical aspects, genetic heterogeneity, gene mapping and
      the problems related to genetic counseling.

PMID- 14688979
TI  - [Morbidity due to violence against children and adolescents in Rio de Janeiro].
AB  - An analysis of police records was carried out in the Programatic Areas (Aps) of
      the city of Rio de Janeiro in 1990. 8000 non-fatal records were investigated,
      covering children and adolescents from 0 to 19 years old. These violent events
      were categorized as traffic accidents, physical abuse, robbery/theft and attempt
      of robbery/theft, sexual abuse, extortion/sequestration, threat, neglect
      abandon,drugs use/traffic, and attempt of suicide/homicide. The aim of this paper
      is to identify the most frequent type of violence in the different Aps. According
      to the findings, traffic accidents, physical abuse and robbery/theft are the most
      common violent events affecting, especially boys in 10-19 age group. The APs 1
      and 3.3 show the highest rates. The article concludes with difficulties and
      possibilities of dealing with violence in the health field, especially in the
      professional training.

PMID- 14688980
TI  - [Domestic violence against children (First Part)].
AB  - The authors interviewed 76.2% of the pediatricians from the Pediatric Department
      School of Medical Sciences-Campinas University-UNICAMP, to analyse the
      difficulties of this professional group in the evaluation of the domestic
      violence against children. From the group of professionals, 86.7% had already
      attended a situation involving child abuse; the therapeutic aspects were referred
      in 44.4% as most important, and in 46%, the difficulties in the diagnostic
      aspects were referred. They conclude that, despite the experiences with the
      theme, a lot more could be done and studied.

PMID- 14688981
TI  - [Myelomeningocele: surgical treatment and results].
AB  - The authors made a retrospective study of 72 patients with myelomeningocele
      treated at a pediatric hospital in Rio de Janeiro, Brazil. 65 (90.2%) lesions
      involved the inferior segments of the spine and 87.5% of the patients needed
      shunt procedures for hydrocephalus control. Shunt infections in spina bifida
      cystica patients were more frequent than in any other group of hydrocephalic
      patients treated at the institution. There was a great incidence of postoperative
      complications such as wound infections and skin necrosis. 11 (15.3%) patients
      developed signs and symptoms related to Chiari II malformation. The overall
      mortality was 8.3%, and in most of the cases, ascribed to the Chiari
      malformation.

PMID- 14688982
TI  - [Management of febrile infants younger than 2 months of age at the Emergency Care
      Unit: diagnosis aspects and therapeutics].
AB  - 82 febrile young infants were studied, prospectively, at the Emergency Service in
      Hospital Universitario-University of Sao Paulo. All the children were kept at the
      Emergency ward for 24 hours. Clinical and laboratory investigations were
      performed and when necessary, administration of antibiotic agents were started.
      18 infants exhibited potentially severe bacterial infections (21.9%). Several
      important disorders were recognized in 40 infants (48.8%). All infants were
      followed until the end of the febrile episode: 20 children as inpatients and 62
      as outpatients. 38 infants received antibiotic therapy (46.3%). Evolution was
      satisfactory in all patients. The authors detected in young febrile infants
      potentially dangerous clinical conditions that need close observation,
      laboratorial investigation and frequently antimicrobial therapy. The observation
      period at the Emergency ward was important to allow these procedures and to
      decide about hospitalization need.

PMID- 14688983
TI  - [The influence of the mode of delivery on the umbilical cord serum aldosterone
      levels in preterm newborn infants].
AB  - The influence of the mode of delivery on the umbilical cord serum aldosterone
      levels in preterm newborn infants was studied. Sixty-four newborn infants
      gestational age less than 37 weeks were sequentially included in the study.
      Umbilical cord blood was collected just after birth and the aldosterone level was
      measured by radioimmunoassay. The median aldosterone level of the whole studied
      sample was 74.5 ng/dl (range: 22.00-280.00 ng/dl). The aldosterone level of the
      31 newborn infants delivered vaginally was similar of the 33 newborn infants
      delivered by cesarean-section. When the cesarean group was subdivided in presence
      or not of labor prior to delivery, the aldosterone levels of those delivered
      after labor was significantly higher than those without labor. It is suggested
      that some event associated to the mode of delivery or the presence of labor prior
      to delivery may influence aldosterone levels in preterm newborn infants.

PMID- 14688984
TI  - [Beals-Hecht Syndrome: report of a neonatal case].
AB  - Congenital contractural arachnodactyly (CCA) is an inherited disorder of
      connective tissue. The most characteristic features are arachnodactyly, multiple
      congenital contractures, dolichostenomelia, deformed external ears,
      kyphoscoliosis and camptodactyly. We report a case of CCA diagnosed at birth.

PMID- 14688985
TI  - [Trichosporon beigelii peritonitis in a child during treatment by continuous
      ambulatory peritoneal dialysis].
AB  - We report a case of peritonitis caused by Trichosporon beigelii in a 2-year-old
      child during treatment by continuous ambulatory peritoneal dialysis (CAPD).
      Diagnosis was established by direct examination and culture of dialysis effluent.
      Infections caused by Trichosporon beigelii in children are commented.

PMID- 14688986
TI  - [Cockayne syndrome in two brothers].
AB  - We report the clinical history of two brothers with the classical Cockayne
      syndrome. The main manifestations consisted of cachectic dwarfism, mental
      retardation, intracranial calcifications, microcephaly, enophthalmos, senile
      appearance, joint hypomotility and skin photosensitivity. In one of these
      children, who died at 10 years of age of bronchopneumonia, necropsy studies
      revealed a variety of anomalies, mainly encephalic,which included an arachnoidal
      cyst at the base of the cerebellum, a defect apparently previously undescribed
      inpatients with this syndrome.

PMID- 14688987
TI  - [Hepatic dysfunction and parenteral nutrition].

PMID- 14688988
TI  - [Visceral Leishmaniasis (Kala-azar)].

PMID- 14688989
TI  - [Mucosal immune response development: breastfeeding and environmental influence].
AB  - A review of the current knowledge of mucosal immune response development
      indicates that migration of immunocytes to mucosal surfaces is an early event
      during fetal life. The morphologic development of gut-associated lymphoid tissues
      (lymphoid follicles, Peyer's patches and tonsils) occurs from 11-20 weeks'
      gestation upwards. But they are active only after birth, when usually antigenic
      challenge takes place. The complete development of secretory immunity is a
      postnatal achievement. In infancy, some environmental factors such as feeding and
      oral antigenic challenge seems to modulate immune response development.
      Breastfeeding, by means of antiinfectious, antiinflammatory and immunomodulating
      properties, besides completing infant secretory immunity, also stimulates
      immunological maturation on mucosal surfaces.

PMID- 14688990
TI  - [Television and sexual education].
AB  - The author describes television as a factor of influence in the sexual
      (mis)education in adolescence. He considers the role of eroticism in television
      as a dysfunctional factor in the sexual education of youth. In accordance with
      its pervasion, accessibility and attractive and seductive contents TV may be
      considered an alternative source and an efficient instrument of sexual
      (mis)education, because adolescents find in it a lot of information that
      satisfies their curiosity about the sexual world of adults. This occurs through a
      process of more and more explicit eroticism that abuses the freedom of sexual
      expression and exhibition and transmits all kinds of sexual information:
      faithful, correct, tendentious, preconceptual, ambiguous and distorted.

PMID- 14688991
TI  - [Parenteral nutrition related cholestasis: infection as the main risk factor].
AB  - Total parenteral nutrition-associated cholestasis (TPN-AC) is a clinical problem
      of special interest in neonates and in other age groups. This retrospective
      cohort study attempted to determine the incidence and the appearing time of
      cholestasis in Intensive Care Unit (ICU) patients beyond neonatal period,
      submitted to total parenteral nutrition (TPN) for more than five consecutive
      days, focusing on the relation of TPN-AC and severe infection. Data on one
      hundred and thirteen patients, aged from one month to 14 years, collected over a
      period of ten years, were analyzed. All patients, followed up to the TPN stop or
      their death, were classified in two groups: with and without cholestasis. They
      were evaluated in relation to cholestasis potential risk factors, such as severe
      infection. Cholestasis was identified by a conjugated bilirubin (DB) and total
      bilirubin rate equal or superior to 40% and/or a DB equal or superior to 0.5
      mg/dl during the TPN laboratory monitoring. Logistic regression analysis was used
      to control and to adjust for the cholestasis confusion factors. The incidence of
      cholestasis was 18%, but it was very important in patients younger than 6 months
      (26% vs 12%) (p=0.06), in patients that use TPN for more than 2 weeks (25% vs 8%)
      (p=0.01), as well as in patients with severe infection (24% vs 3%) (p=0.02). On
      the average cholestasis appeared 17.6 days after TPN inception, with a range of 5
      to 35 days. Control of the simultaneous effect of age, TPN duration, and severe
      infection has shown that in patients with less than 6 months the relative risk
      was 2.6 (NS); in patients with TPN longer than 2 weeks it was 3.1 (p=0.02); and
      in patients with severe infection it was 7.4 (p=0.006). The results suggest that
      TPN-AC in children beyond neonatal period is a relatively frequent event (18%),
      and severe infection is the most important risk factor for cholestasis.

PMID- 14688992
TI  - [Clinical and epidemiological features of Kala-Azar in children].
AB  - The author reviewed the records of 75 patients under thirteen years old, with
      Visceral Leishmaniasis, admitted in the public hospitals of Brasilia, during the
      period from January 1982 to June 1991. All children were referred to Brasilia
      hospitals from other states of the country, and most of them from the rural areas
      of Bahia state. In 78.6% of the patients the diagnosis of Visceral Leishmaniasis
      was confirmed one to six months after the appearance of the first clinical sign
      of the disease. The clinical manifestations observed in this study were similar
      to those previously described in the literature. Moderate to severe malnutrition
      was present in half of the patients. The laboratory tests showed expected results
      for the disease. All patients were treated with N-methyl-glucamine, and this
      therapeutic was successful in 91.4% of the children. The complications more
      frequently seen were infections and hemorrhage. There were 7 deaths due to
      pneumonia with respiratory failure and digestive bleeding.

PMID- 14688993
TI  - [Validation of therapeutic test in the diagnosis and treatment of Kala-Azar in
      children].
AB  - The author studied the value of therapeutic test for the diagnosis and treatment
      of kala-azar in children by comparing two groups of patients. The identification
      of Leishmania donovani in smears of bone marrow confirmed the diagnosis in all
      fifty seven patients of the control group. In another group with sixteen
      children, the diagnosis was based on the successful response to the treatment
      with meglumine antimonate. In none of the patients of the second group the
      protozoa was identified and the decision to give the specific treatment was based
      on epidemiological, clinical, biochemical and hematological criteria for the
      disease. Statistical analysis was performed by Student t test to compare
      clinical, biochemical and hematological variables between the groups. None of the
      differences between the groups was statistically significant, suggesting that the
      therapeutic test was valid, and all patients who received treatment had kala
      azar.

PMID- 14688994
TI  - [Risk factors for childhood asthma in Fernando de Noronha: a case control study].
AB  - Fernando de Noronha Island, because of its ecological characteristics,has
      virtually no atmospheric pollution that could cause asthma. Nevertheless, asthma
      prevalence in children younger than 6 years old is 11.22%. 17 asthmatic children
      and 68 healthy ones were included in this case control study (1:4 case/controls)
      conducted in a closed community free from atmosphere pollution. Maternal asthma
      and exposure to smoking were more frequently associated with asthmatic children
      than with controls, the risk of asthmatic syndrome being respectively 6.9 and 4.6
      times bigger. As for breastfeeding no protective effect was found in both cases
      and controls.

PMID- 14688995
TI  - [The Steatocrit Test: a semiquantitative method to evaluate the fecal fat
      excretion--method standardization].
AB  - The main objective of this study was to introduce among us this technique. In a
      first step, steatocrit was compared to Van de Kamer test for 30 fecal samples. A
      significant positive correlation was found. In a second step, a steatocrit value
      was determined for normal children aged 0 to 72 months. In children from 0 to 3
      months of age, no influence was found of diet (whether exclusively maternal milk
      or artificial one) on steatocrit value. However, upto the age of 3 months a
      significant and negative correlation was found between age and steatocrit value.
      Finally, three age groups were identified with different steatocrit values, as
      follows: 0-1 month, 4.04%; 1-3 months, 1.38%, 3-72 months, 0.29%. Thus the
      steatocrit test for fecal fat excretion was again shown to be not only simple,
      rapid, painless and inexpensive but also a reliable one.

PMID- 14688996
TI  - [Management of a case of maple syrup urine disease--the use of gluco
      insulinotherapy].
AB  - We report here the treatment and poor outcome of a case of Maple Syrup Urine
      Disease with late diagnosis and retrieval (2 and 5 months, respectively). As the
      proband had quite high levels of plasmatic leucine (1956 micromol/L for a normal
      upper limit of 77), we started immediately with a gluco-insulin therapy to
      produce anabolism in the infant. When leucine has fallen to 275.3 micromol/L, we
      instituted feeding with branched chain amino acid-free protein and high energy
      from carbohydrates. After reviewing briefly the clinical, biochemical and
      therapeutic aspects of this disorder, we comment on the great difficulties of
      making early diagnosis and of obtaining the specific dietetic formulas to Maple
      Syrup Urine Disease, in Brazil.

PMID- 14688997
TI  - [Breast-feeding: women's view and the world breastfeeding week].

PMID- 14688998
TI  - [Initial cardiological examination in pediatrics: it's role in primary
      attention].

PMID- 14688999
TI  - [Vesicoureteral reflux in children].
AB  - The association between vesicoureteral reflux and urinary tract infection
      represents a significant threat to the kidney, in the form of pyelonephritic
      scarring. The physiopathologic events that allow the upward migration of bacteria
      and their inoculation in the renal tissue, causing irreversible damage if not
      adequately treated, are reasonably understood. Reflux nephropathy is a major
      cause of childhood hypertension and renal insufficiency. Early diagnosis of
      reflux, and identification of the pyelonephritic aggression are important for
      successful therapy. Long-term chemoprophylaxis,to prevent urinary tract infection
      and renal scarring is the adequate form of treating low-grade vesicoureteric
      reflux, since spontaneous cure is expected in most of these cases. Although the
      same approach can be employed in high-grade reflux, surgery is a favorable
      alternative, with high rates of primary success,reducing the need of long-term
      medication and the exposure of the kidney to recurring pyelonephritic aggression.
      The retrograde flow of urine from the bladder to the upper urinary tract is an
      abnormal situation in the human being, known as vesicoureteral reflux (VUR). It
      results either from an intrinsic anatomical deficiency of the vesicoureteral
      junction or from an increased bladder pressure, due to mechanical or
      dysfunctional vesicourethral obstruction. The recognition of the association
      between VUR, urinary tract infection (UTI) and renal scars has led to an
      increased study of this disease in the last two decades.

PMID- 14689000
TI  - [Indications of phototherapy for full term newborn infants with non-hemolytic
      hyperbilirubinemia: a critical analysis].
AB  - Phototherapy is a common procedure in the neonatal period. However there is great
      controversy in the literature about when and at which serum bilirubin levels
      phototherapy and exchange transfusion should be indicated. The aim of this paper
      is to review the literature and to suggest guidelines to help pediatricians in
      deciding when to treat non-hemolytic jaundice in full-term newborn infants.

PMID- 14689001
TI  - [Breast-feeding--the view of women who breast-feed].
AB  - This is a qualitative study, the result of questions about breast-feeding in
      terms of the meaning it has for the woman who experiences it. The
      phenomenological theoretical background led to understand breast-feeding based on
      the dimension of a being who breast-feeds. Thus, we sought the discourse of women
      using the following guiding question: "What did it mean for you to experience
      breast-feeding?". Analysis of the discourses as a whole revealed that the breast
      feeding experience affects the various possibilities of woman's being in the
      world with others. From this perspective, new horizons were opened with respect
      to thinking, experiencing and educating for breast-feeding.

PMID- 14689002
TI  - [Analysis of the efficacy of the maternal breast-feeding incentive program in a
      peripheric district of Belo Horizonte (Brazil): 1980/1986/1992].
AB  - Three institutions worked together in order to combat early weaning in a
      peripheric district of Belo Horizonte (Brazil): the Department of Pediatrics of
      the Faculty of Medicine (Federal University of Minas Gerais), the Secretary of
      Health of Belo Horizonte and a Brazilian assistential institution ("LBA"). One
      initial survey, in 1980, documented breast-feeding practices in this community,
      when there were no systematized actions of incentive to human milk, at local or
      national levels. Two similar surveys were also conducted, in 1986 and in 1992. In
      each one, 152 mothers with children under two years old were randomly selected
      and interviewed. The results showed significant progress in the breast-feeding
      period in the first six years, and a stabilization between 1986 and 1992. For
      example: if only 39.0% of the children received human milk for six months or more
      in 1980, 54.3% received it in 1986 and 52.4% in 1992. In 1980, 80.6% of the
      children were nourished with cow's milk before three months of age, to 56.5% in
      1986 and 56.3% in 1992. Prenatal influence to increase the level of breast
      feeding has always been weak. Besides, a reflux was detected in the last few
      years with regard to the participation of the maternity hospital in the educative
      process.

PMID- 14689003
TI  - [Cardiac evaluation in children with suspected heart disease. Preliminary results
      in 2000 patients].
AB  - Two thousand consecutive children have been evaluated for suspected heart disease
      in a 27-month period. The main reasons for referral were: murmur (70%),
      precordial pain (9.5%), suspicion of arrhythmia (8.5%) and breathless (5%). Five
      hundred and six (25%) cases did not complete the investigation and the results
      were not computed. A final diagnosis was obtained based on the reason for
      referral and the main conclusions were: 1) a high incidence of normality was
      found: murmur (83%), pain (98%), arrhythmia (97%) and breathless (94%); 2) heart
      disease is unlikely when other referral reasons were analyzed; 3) 14% of the
      children were considered abnormal and the necessity of therapeutic procedures was
      0.8%. A pediatric cardiology outpatient clinic in a public setting seems to be
      justifiable in the region, due to the high current demand.

PMID- 14689004
TI  - [Nutritional, psychological and social aspects of mothers of malnourished
      children].
AB  - Mothers of malnourished children were evaluated by psychologist, nutritionist,
      social worker and pediatrician with the objective of verifying in which ways the
      psychological, social and nutritional aspects interact. All mothers were from the
      low socioeconomic level, with extremely low family incomes, lower school levels
      were predominant,with 57.6% up to 4 years of formal education; 27.3% of the
      mothers were single, 48.5% single with male partners, 18.2% married and 6%
      separated. Main personality traits found: immaturity, difficulties in
      relationships, low self-regard, feelings of insufficiency/inferiority,
      aggressiveness. The intellectual level was average or below average in 82.6%.
      Concerning food preparation,we observed that 80% were disorganized and showed
      poor hygiene, 64% did not show interest, 77% wasted foodstuffs, 61.9% were
      insecure in handling foods and 37% prepared foods with inadequate aspect and
      consistency. Results confirm that social aspects effectively are a risk factor
      for malnutrition in families from the low socioeconomic level. Other aspects are
      also very relevant, since certain characteristics of the mothers personality
      disturb her performance and determine external disorder and absence of interest
      during preparation of meals, an activity directly related to child care.

PMID- 14689005
TI  - [Intestinal parasites in children aged 4-12 months attending day-care centers of
      Federal University-Uberlandia-MG].
AB  - The objective of this study was to search for the presence of intestinal
      parasites in 56 suckling babies, ranging from 4 to 12 months in age hosted during
      the year of 1989 at the nursery kept by the "Universidade Federal de Uberlandia",
      at Uberlandia, Minas Gerais State, Brazil. From each child a foecal sample was
      collected and preserved in 10% formalin until processed, what was done by the
      Hoffman, Pons and Janer's method, in which the sediment is stained by lugol
      solution. For each sample 6 slides were prepared and examined, what added up to a
      total of 336 slides. The percentual of positivity was 23.21%, including 17.85%
      Ancylostomidae eggs, 5.36% Giardia lamblia and 1.78% Endolimax nana. Only one
      child presented the associated infections of Ancylostomidae and Giardia lamblia.
      In what host age is concerned, one child was shown to be infected by
      Ancylostomidae after it reached 6 months; generally speaking there was evidence
      of an increase of parasitic infections of hosts beyond the age of 9 months. The
      above results point out to the necessity of searching for the presence of
      parasitic intestinal infections covering suckling babies in public nurseries, by
      means of foecal semestral examinations,even when such babies do not manifest
      clinical signs of parasitism, in order that adequate treatment and preventive
      sanitary measures may be adopted to avoid or suppress ambiental contamination
      with the causative organisms.

PMID- 14689006
TI  - [Abnormal sweat test in patient with Diabetes Insipidus unresponsive to ADH].
AB  - Increased sweat concentrations (92, 76 and 80 mEq/l) were observed in a 7-year
      old boy with pitressin-resistant diabetes insipidus. All previous observations of
      elevated sweat electrolytes in diabetes insipidus have been in infants less than
      10 months of age. The sweat test is an exceptionally reliable, sensitive and
      specific test for the diagnosis of Cystic Fibrosis. Pitressin-resistant diabetes
      insipidus is one of the diseases associated with elevated sweat test results.

PMID- 14689007
TI  - [Evaluation of nutritional status].

PMID- 14689008
TI  - [Maternal cigarette smoking effect upon the fetus].

PMID- 14689009
TI  - [Varicella vaccine].
AB  - The varicella vaccine developed by Takahashi and cols. in 1974, in Japan, shows
      outstanding features. Its development, site and route of administration and final
      results are reviewed in this article.The varicella vaccine is highly effective in
      normal children (with almost 100% seroconversion rate), and with good protective
      responses in immunocompromised children (82% to 90% seroconversion rate). This is
      the first attenuated live virus vaccine that may be recommended for these
      patients. Its indications and side effects, along with needed precautions and
      contraindications are reviewed. Simultaneous administration of varicella vaccine
      with other vaccines can be done, each vaccine should be injected at different
      sites. New studies are ongoing for the association of the varicella vaccine with
      others vaccines. Several countries licensed this vaccine for administration in
      selected high-risk individuals. Probably, in the future, the varicella vaccine
      will be included in the preventive immunization schedule.

PMID- 14689010
TI  - [Epidemiology applied to the investigation of infant health determinants: basic
      concepts and methods].
AB  - Epidemiologic principles and methods have been widely employed in clinical
      research. The purpose of this paper is to discuss basic epidemiological concepts
      applied to the investigation of the determinants of infant diseases. The
      theoretical framework outlines the hypothesis of the investigation. The design of
      the study is chosen accordingly. Exposure and outcome are defined, and the
      sampling criteria and the strategies for its implementation are specified. The
      researcher can be an observer (as in cross-sectional, cohort and case-control
      studies) or can determine who will be exposed in the experimental studies
      (clinical trials). Cross-sectional study is the easiest one to conduct, since
      exposure and outcome are assessed simultaneously in a well-defined population. In
      a cohort study, a group of people is assembled according to the exposure and
      followed over time to detect who will develop the outcome. In a case-control
      study,people are selected based on disease status. Then, they are investigated
      about previous exposures which could be associated with the development of the
      disease. The investigator allocates the exposure and then follows the
      participants to assess the outcome in clinical trials. Contrasting with the
      experiment developed in laboratory, the subjects are human beings.

PMID- 14689011
TI  - [Nutritional status of young children: a comparison among three anthropometric
      classifications].
AB  - OBJECTIVE: to compare the usefulness of the methods proposed by Gomez, Waterlow
      and W.H.O., to classify the nutritional status of children under 2 years of age.
      METHOD: the nutritional diagnosis of 436 infants was defined at 6, 12, 18 and 24
      months of age, using the three proposed methods. Predictive values, positive
      (PV+) and negative (PV-), and agreement coefficient (K) were calculated,
      comparing the nutritional classification of the children on each method with a
      gold standard of nutritional diagnosis, based on individual growth performance
      since their birth. RESULTS: the three methods showed a good PV-, nearby 0.9, at
      all tested ages whereas the PV+ and K exhibited lower values. Among the three
      methods of classification of nutritional status, the method proposed by Gomez
      achieved the best levels of PV+, PV- and K, at all considered ages, mainly at 18
      and 24 months of age. CONCLUSIONS: the Gomez' method, as an unique criterion, is
      better than the others, because it has a lower risk of misdiagnosing a case of
      malnutrition. Nevertheless, this risk is big enough to not recommend its isolated
      use, mainly during the first year of life,when the risk of a false positive
      diagnosis of malnutrition is still higher.

PMID- 14689012
TI  - [Tissue weight and histologic alterations in pregnant rats submitted to
      malnutrition and chronic nicotine distress, and in their neonates].
AB  - The effects of a gestational exposure of 80 rats Wistar EPM-1 to nicotine and
      undernutrition was examined. The weight and histological alterations on the liver
      and lungs was evaluated on the rats and their offspring. A significantly lower
      weight gain, including liver and lung weight, was observed in nicotine exposed
      groups. There was no alteration of the placental weight. Decidual necrosis and
      hepatic congestion was frequent in the rats. Lung emphysema was found in the
      neonates.

PMID- 14689013
TI  - [Psychosocial and sexual aspects of pregnant adolescents at Belem-Para].
AB  - Pregnancy is a major factor that modifies psychosocial aspects of the
      adolescents. A study with 120 pregnant adolescents aged 12 to 18 years, without
      regarding gestational age, was carried out at Prenatal Risk Program in the
      Secretaria Estadual de Saude, Belem-Para, from 10/1991 to 04/1992. At the first
      encounter, it was made an approach of psychosocial and sexual subjects, with the
      following results: onset of menarche primarily between 12-13 years old (median
      12.2 years old); beginning of sexual practice at 14 years old in 50.9% of the
      adolescents. 56.6% were pregnant at 16 years old. Most of the adolescents (98.4%)
      first had sexual intercourse with their boy friends and by their own wish
      (72.5%). In one year of loving affair, 67.5% of the adolescents have already
      begun sexual activities, this attitude more prevalent among the younger(79.4%).
      Adolescents had learned about sexuality mainly from mates (65.1%). Although 55.9%
      of the adolescents were aware of some contraceptive method, just 13.3% of them
      used one. The majority of the pregnant adolescents (96.7%) were financially
      supported by their families. Respectively, 30.3% and 32.1% of these girls left
      school before or during pregnancy. The risk factors that may contribute to an
      early and unintended pregnancy among adolescents, specially the younger ones,
      were pointed out: little information about sex and contraceptive methods, limited
      practice on their use and a high rate of precocious sexual activities.

PMID- 14689014
TI  - [Proliferation of anaerobic flora in the small intestine of infants with acute
      and protracted diarrhea].
AB  - Bacterial proliferation in the small intestine can induce the protraction of
      diarrhea due to malabsorption of the nutrients. We performed the culture of the
      small intestine juice for the aerobic and anaerobic flora in 40 infants with
      persistent and acute diarrhea. Bacterial proliferation was observed in 32 (80%)
      patients, being 30 (75%) due to the aerobic microflora and 17 (43%) due to the
      anaerobic microflora. There was no statistical difference in the bacterial growth
      between acute and persistent diarrhea. The aerobic bacteria most frequently
      isolated was E. coli in 23 patients, and Bacteroides sp was the most prevalent
      anaerobic bacteria, isolated in 9 cases. The transitory flora was significantly
      more abundant in patients with persistent diarrhea.

PMID- 14689015
TI  - [Congenital malaria in the county of Leme, SP].
AB  - Congenital malaria associated to Plasmodium vivax in a newborn baby (14 days old)
      is reported. The mother lived in a malaria-prone area, and came up to the county
      of Leme, Sao Paulo state, 40 days before baby's birth. Congenital malaria was
      classified through precocious symptoms, absence of malaria in the county and no
      history of blood transfusion or parenteral intervention of any sort. The case
      arises interest because of the necessity of malaria diagnoses suspicion on
      febrile newborns in non endemic areas, since the mother have lived or stayed in a
      malarious region.

PMID- 14689016
TI  - [Neonatal arthritis of the hip due to group B streptococcus].
AB  - The authors describe a case of neonatal osteoarthritis of the hip due to group B
      streptococcus and discuss the importance of recognizing this bacteria in the late
      focal infections of the newborn.

PMID- 14689017
TI  - [Nutritional anemia: prevention or treatment?].

PMID- 14689018
TI  - [Bronchodilator dry powder inhaled in acute asthma].

PMID- 14689019
TI  - [Vaccines against meningococcal disease].
AB  - The meningococcal disease has been a source of preoccupation all over the world.
      Epidemics have been registered periodically in developed or developing countries.
      The most frequent meningococci are those concerned with serogroups A, B and C.
      Researches to develop effective vaccines against the disease have been taking
      place since the 40's. Presently, only vaccines against the meningococci from the
      serogroups A, C, Y and W-135 are available. These vaccines have important
      limitations both due to the age range that they protect and the period of time
      that the protection lasts. They are not routinely used in vaccination programs
      and are indicated only in risky situations. This demands a strict epidemiological
      surveillance of the disease. There are no vaccines against the serogroup B
      meningococci with recognized effectiveness, although, in the last decades, many
      have been tested. There are perspectives of important advances in this area,
      mainly with the development of conjugated vaccines, like the Haemophilus
      influenzae type B vaccine. Until the present, the chemoprophylaxis of the
      intimate communicants of a case is the best way to avoid secondary cases.

PMID- 14689020
TI  - [Iron content of infant diets cooked in iron utensils].
AB  - Iron deficiency is the most frequent form of nutritional anemia, and infants
      represent one of the major risk groups. The present study was meant to evaluate
      the iron content of infant diets cooked in iron utensils and in aluminum utensils
      prepared by volunteer mothers at home. The iron content was analyzed by atomic
      absorption spectrophotometry. The increase of iron in diets cooked in iron
      utensils was 12 to 44 times greater than in diets cooked in aluminum utensils.
      The pH and moisture of the diets cooked in the two types of utensils did not
      differ in a statistically significant manner. On the basis of these results, it
      was estimated that the increase in daily iron supply obtained by cooking the diet
      in iron utensils would be sufficient to satisfy the iron requirements of infants.

PMID- 14689021
TI  - [Accidental extubation in a pediatric intensive care unit].
AB  - It is an on-going practice in the pediatric ICUs to obtain and to maintain a
      working artificial airway. Nevertheless this procedure bears not infrequent risks
      of accidental extubation (AE) which ranges in several services from 0.9 to 3.3
      for each 100 days of intubation. The risk factors that are involved in AE are
      related to: sedation level, age-group, intubation path, and others. The purpose
      of the authors in this article was to observe the incidence of AE in their
      service and to compare the relative risk in the rate of AE among orotracheal and
      nasotracheal intubation population. A prospective study was taken during six
      months, in which every patients with artificial airway admitted at the PICU of
      the Santo Antonio Hospital in Porto Alegre (Brazil) was included except those
      with tracheostomy. The total number of cases were 673 patients-day with
      artificial airway, with an average of 3.7 patients with tracheal tube per day. In
      the period there were 18 AE, with a rate of 2.7 AE/ 100 days. The incidence rate
      of AE in the orotracheal group was 3.1% and 1.6% in the nasotracheal group with
      no statistically significant difference (p=0.6). The authors concluded that the
      pathway of intubation in their study does not carry any additional risk in the
      incidence of accidental extubation.

PMID- 14689022
TI  - [Maternal knowledge on breastfeeding and related factors].
AB  - The influence of maternal knowledge about breastfeeding on the initiation and
      duration of lactation has been described. The present study evaluated the
      maternal knowledge about breastfeeding and its relationship with prenatal and
      postnatal orientation and prevalence of breastfeeding at 3 months. A cross
      sectional study was designed involving 100 mothers of first-born babies between 6
      and 12 months old receiving medical care in the Hospital de Clinicas de Porto
      Alegre. The mothers answered a standardized questionnaire containing 14 questions
      to test knowledge on breastfeeding. The majority of mothers (62%) could not
      answer correctly half of the questions. Those more educated, who received
      prenatal orientation about breastfeeding and who had at least 5 prenatal visits
      had better knowledge. On the other hand, mothers who received postnatal
      orientation did not present a better knowledge. Prevalence of breastfeeding at 3
      months was not related to maternal knowledge on the subject. The maternal
      knowledge about many aspects of breastfeeding was low. Postnatal orientation did
      not increase this knowledge. On the other hand, prenatal orientation had a
      positive impact on maternal knowledge about breastfeeding. Nonetheless this
      increase in knowledge was not sufficient to interfere with the prevalence of
      early interruption of breastfeeding.

PMID- 14689023
TI  - [Effect of inhaled terbutaline sulphate (dry powder, Turbuhaler and nebulizer
      solution) in children with acute asthma].
AB  - Forty seven children (6-14 years), with an acute mild or moderate attack of
      asthma (clinical score 3 or FEV1 > 50% of the predicted), were treated with
      terbutaline sulphate, by inhalation route with a dry powder inhaler (Turbuhaler -
      0,5 mg - group T; N=27, or by a nebulizer 1% solution-in saline-compressed air (6
      l/min.) group S; N=20. The children were evaluated at 5, 15, 25 and 30 minutes
      after the initial treatment. In both groups a significant fall of the clinical
      score (starting at 15 minutes) (p < 0.05) and a significant improvement of the
      FEV(1), VC and FEF25-75% (starting at 5 minutes), were observed (p < 0.05). There
      were no significant changes in heart rates, respiratory rates and blood pressure
      (p > 0.05). At the end of the first treatment, the number of patients with a
      FEV(1) < 80% was similar in both groups (T = 13/27 and S = 10/20). The same
      treatment was repeated, and all the children showed a marked improvement, except
      for one boy of the group T was hospitalized. In conclusion, children with mild or
      moderate acute attacks of asthma can be treated up to a week with an inhalation
      of dry powder, resulting in adequate bronchodilatation without important side
      effects.

PMID- 14689024
TI  - [Down Syndrome--a clinical, cytogenetic and epidemiologic analysis of 165
      patients].
AB  - A clinical follow up of 165 Down Syndrome (DS) patients in an outpatient clinic
      programme at the Centro de Genetica Medica (IFF - FIOCRUZ) was undertaken
      retrospectively. Clinical and laboratorial investigations were performed, such as
      cytogenetics and hematological analysis, thyroid hormones survey, abdominal
      ultrasound and cervical column X Rays. The clinical diagnosis of Down Syndrome
      was mostly performed during the first year of life, and 70% of all patients were
      under 4 years of age, being predominantly males. Trisomy 21 derived from non
      disjunction was found in 85% of the patients. The most common congenital
      malformation was cardiopathy (37.5%) and among all the clinical complications,
      repeated pneumonia could be evidenced in 30% of the patients, mainly during the
      first year of life. Leukopenia was observed in 14% of the patients and abdominal
      ultrasound scans allowed the early detection of biliary stones in 4.3% of the
      patients examined, a significative finding in the paediatric population. A
      prospective clinical programme aiming to anticipate the detection of clinical
      complications on at risk DS populations will fulfill its objectives and may act
      as a reducing factor in the infantile mortality rate.

PMID- 14689025
TI  - [Accessory perineal scrotum].
AB  - Congenital anomalies of genital region frequently occur but congenital scrotal
      anomalies are not common and few cases have been reported in the literature.
      Among these reported anomalies the accessory scrotum is the lowest incidence
      principally when not associated with other congenital anomalies. The authors
      reports a case of accessory perineal scrotum without associated anomalies.

PMID- 14689026
TI  - [Early diagnosis of childhood deafness and therapeutic workup].
AB  - The aim of this paper is to emphasize the importance of hearing as the main
      component of human communication, the identification of the risk group for
      hearing deficiencies and the role of brainstem evoked auditory potentials as an
      early detection method, which is essential for starting both medical and
      educational intervention in order to optimize the child's communication
      development and social abilities. The author presents a case report of a severe
      hearing loss patient whose diagnosis was done on his first day of life.

PMID- 14689027
TI  - [Fetal and neonatal growth. Should we use national growth charts?].

PMID- 14689028
TI  - [True precocious puberty in girls].

PMID- 14689029
TI  - [Decision making about the child in CIU--participation of the family].
AB  - This paper focuses attention on the moral and ethical principles in the treatment
      of a very sick newborn infant and child. Special attention is given to the risk
      benefit balance of the employment of sophisticated technology with the purpose of
      prolonging the survival of a possible handicapped child. The authors analyzed the
      different ways of facing this problem according to different cultural
      backgrounds. The concept of a terminal patient is not applied to the neonatal
      period. The principle of autonomy is discussed, and the familiar feelings are
      analyzed.

PMID- 14689030
TI  - [Intrauterine growth curves: study of 4413 single live births of normal
      pregnancies].
AB  - Having the purpose of identifying those newborn who have suffered from abnormal
      intrauterine growth, a standard of intrauterine growth has been drawn at the
      maternity ward of Hospital Regional da Asa Sul (HRAS-FHDF-Brasilia), by studying
      the variables of weight, length, cephalic perimeter, weight of the placenta (with
      the cord and membranes), weight rate and the relative placentary rate. The
      starting number of 8,271 live births which happened between July 1989 and March
      1991 was cut down to 4,413 due to the exclusion of interfering factors of foetus
      growth (smoking mother, multiple gestation, hemorrhage during the 2nd and 3rd
      trimesters chronic anaemia, arterial hypertension, pre-eclampsia and eclampsia),
      in addition to the exclusion of those mothers who could not remember the date of
      their last period or were in doubt about it. Comparing this standard of
      intrauterine growth to the ones in literature, the present values are higher,
      most of the times, from weeks 30 to 37-38, and after that there is a slowing down
      similar to the pattern observed in placentary growth. This study proposes a
      standard adequate to the assessment of intrauterine growth in Brasilia and other
      regions, mainly at the Centre-West Region, where the population should be similar
      to the one studied here.

PMID- 14689031
TI  - [Growth of preterm infants].
AB  - A hundred-forty-one infants born from 26 to 36 weeks, appropriate-for-gestational
      age, were followed from birth until the corrected postmenstrual age of 42 weeks.
      Weight, height and cephalic perimeter were measured on a weekly basis. Based on
      the average values and percentiles of these measurements it was adjusted a third
      degree polynomial function. The growth curves obtained, when compared with the so
      called intra-uterine growth curves, showed that during the 40th and 42nd
      postmenstrual weeks the averages and medians are similar. It was observed that
      the growth dynamics of the preterm infants showed a catch-up pattern in the
      immediate postnatal period.

PMID- 14689032
TI  - [Incidence of heart defects in Down syndrome].
AB  - Eighty-six patients with Down Syndrome were studied with the main purpose of
      quantifying the incidence of congenital heart defects and the risk of occurrence
      according to the mothers age. Thirty-eight patients had the cariotypes
      determined, 35 of them having trissomy of chromosome 21 and translocation in 3
      cases. Congenital heart disease was found in 44 (51%) of the patients, the most
      common one being ventricular septal defect. An important incidence of Fallot's
      tetralogy was also found (20%). These 86 children were submitted to 41 surgical
      procedures, most of them on the cardiovascular system. The maternal mean age was
      33 -/+ 8.6 years and the estimated risk of Down Syndrome was 1/590, a lower value
      than the one reported in other studies.

PMID- 14689033
TI  - [Atopic diseases in Brazilian children--etiologic multicentric study].
AB  - In order to determine the etiologic agents involved in atopic diseases in
      Brazilian children, we have performed this multicentric study in 8 areas in
      Brazil. We have done prick tests with inhalants and food antigens and analyzed
      skin tests results, considering positive the wheal mean diameter 3 mm. 22,2% of
      skin tests were negative and the majority were positive to inhalants:
      D.pteronyssinus(Dpt) (66.6%) and D. farinae(Df) (66.0%), house dust extract
      (29.0%), dogs epithelium (19.2%), cat's epithelium (8.8%), feather (5.5%), molds
      (4.2%), Penicillium sp (2.2%) and Lollium perene (0.6%). We have had 9,1% of food
      positive tests: cow milk (5.2%), peanut (3.5%), corn (3.2%), cocoa and soya
      (2.2%), eggs and wheat (1.9%). We have concluded that the domestic mites are the
      most important agents involved in the etiology of atopic diseases in Brazilian
      children, and the extracts involved, in line with the sensitization of each
      geographical area.

PMID- 14689034
TI  - [Study of true precocious puberty in girls using clinical, laboratorial and
      imaging techniques].
AB  - This paper reviews the clinical findings, pituitary gonadotrophin reserve, plasma
      estradiol and androgens, radiological findings and pelvic ultrasound appearance
      in 17 girls with true precocious puberty (PP), and attempts to asses the value of
      these tests diagnosis in the clinical management of such patients and better
      understanding of the pathogenesis of this disorder. As noted in other series,
      acceleration of growth is one of the earliest features of PP and at the time of
      diagnosis bone age can be already significantly advanced. In 3 (18%) patients
      intracranial abnormalities were present. Ultrasound examination showed changes
      similar to those seen during normal puberty. To conclude, the introduction of
      high-resolution methods (CT scan and RM) and techniques for ultrasound
      examination have greatly simplified the clinical investigation of female
      precocious puberty.

PMID- 14689035
TI  - [Giant epignathus in the newborn: report of a case and review of the literature].
AB  - Epignathus is a congenital teratoide tumor in the oral cavity. It is extremely
      rare and usually lethal. The authors present a case treated successfully.
      Important aspects of the diagnosis, clinical management and surgical procedures
      are discussed. Extensive review of the literature is presented.

PMID- 14689036
TI  - [Recurrent bronchopneumonia and Morgagni hernia].
AB  - The Morgagni hernia occurs behind the sternum and is a rare diaphragmatic defect
      although the late diagnosis may result in important clinic symptoms and poor
      prognosis. The authors present a case report of a child with 11 months and
      respiratory symptoms with chronic pulmonary infections and several
      hospitalizations without etiologic diagnosis. The conclusion was for the early
      Morgagni hernia diagnosis and the prevention of chronic complications.

PMID- 14689037
TI  - Possible etiologies for tropical spastic paraparesis and human T lymphotropic
      virus I-associated myelopathy.
AB  - The epidemiology of tropical spastic paraparesis/human T lymphotropic virus I
      (HTLV-I)-associated myelopathy (TSP/HAM) is frequently inconsistent and suggests
      environmental factors in the etiology of these syndromes. The neuropathology
      corresponds to a toxometabolic or autoimmune process and possibly not to a viral
      disease. Some logical hypotheses about the etiology and physiopathology of TSP
      and HAM are proposed. Glutamate-mediated excitotoxicity, central distal
      axonopathies, cassava, lathyrism and cycad toxicity may explain most cases of
      TSP. The damage caused to astrocytes and to the blood-brain barrier by HTLV-I
      plus xenobiotics may explain most cases of HAM. Analysis of the HTLV-I/xenobiotic
      ratio clarifies most of the paradoxical epidemiology of TSP and HAM. Modern
      neurotoxicology, neuroimmunology and molecular biology may explain the
      neuropathology of TSP and HAM. It is quite possible that there are other
      xenobiotics implicated in the etiology of some TSP/HAMs. The prevention of these
      syndromes appears to be possible today.

PMID- 14689038
TI  - Autoantibody production in chronic idiopathic urticaria is not associated with
      Helicobacter pylori infection.
AB  - Chronic idiopathic urticaria (CIU) is a dermatological syndrome, characterized by
      raised erythematous skin lesions, that affects 20% of the general population and
      has been associated with autoimmunity. However, some reports have also suggested
      a close relationship between CIU and Helicobacter pylori infection, which is
      endemic in developing countries and associated with chronic gastritis, peptic
      ulcer disease, and gastric carcinoma. In the present study, we investigated the
      occurrence of autoantibodies in sera from 23 CIU subjects infected with H. pylori
      and from 23 CIU subjects without this infection. The presence of anti-thyroid
      antibodies was determined by indirect hemagglutination assay and the presence of
      autoantibodies to IgE and C1INH was determined by ELISA. Antibodies to thyroid
      antigens were detected at low titers from 100 to 400 in three of 23 (13%) CIU
      infected subjects and in four of 23 (17%) CIU-noninfected subjects. The titers of
      anti-IgE autoantibodies were similar in these CIU groups, presenting absorbances
      of 1.16 +/- 0.09 and 1.07 +/- 0.16, respectively, while a titer of 1.14 +/- 0.15
      was detected in the healthy control group. The concentration of anti-C1INH
      autoantibodies was the same in the CIU-infected and -noninfected subjects (7.28
      +/- 1.31 and 7.91 +/- 2.45 ng/ml, respectively), and was 7.20 +/- 2.25 ng/ml in
      the healthy control group. However, the serum levels of complexed anti-C1INH
      antibodies were increased in CIU-infected subjects compared to CIU-noninfected
      subjects and healthy controls with an absorbance of 1.51 +/- 0.21 vs 1.36 +/-
      0.16 and 1.26 +/- 0.23, respectively (P<0.05), indicating an impaired clearance
      of immune complexes in CIU-infected patients. In conclusion, no correlation was
      observed between H. pylori infection and autoantibody production in CIU patients
      consistent with reports of clinical studies.

PMID- 14689039
TI  - Use of neuron-specific enolase for assessing the severity and outcome in patients
      with neurological disorders.
AB  - Neuron-specific enolase (NSE) is a glycolytic enzyme present almost exclusively
      in neurons and neuroendocrine cells. NSE levels in cerebrospinal fluid (CSF) are
      assumed to be useful to estimate neuronal injury and clinical outcome of patients
      with serious clinical manifestations such as those observed in stroke, head
      injury, anoxic encephalopathy, encephalitis, brain metastasis, and status
      epilepticus. We compared levels of NSE in serum (sNSE) and in CSF (cNSE) among
      four groups: patients with meningitis (N=11), patients with encephalic injuries
      associated with impairment of consciousness (ENC, N=7), patients with
      neurocysticercosis (N=25), and normal subjects (N=8). Albumin was determined in
      serum and CSF samples, and the albumin quotient was used to estimate blood-brain
      barrier permeability. The Glasgow Coma Scale score was calculated at the time of
      lumbar puncture and the Glasgow Outcome Scale (GOS) score was calculated at the
      time of patient discharge or death. The ENC group had significantly higher cNSE
      (P=0.01) and albumin quotient (P=0.005), but not sNSE (P=0.14), levels than the
      other groups (Kruskal-Wallis test). Patients with lower GOS scores had higher
      cNSE levels (P=0.035) than patients with favorable outcomes. Our findings
      indicate that sNSE is not sensitive enough to detect neuronal damage, but cNSE
      seems to be reliable for assessing patients with considerable neurological insult
      and cases with adverse outcome. However, one should be cautious about estimating
      the severity of neurological status as well as outcome based exclusively on cNSE
      in a single patient.

PMID- 14689040
TI  - An analysis of the electrocardiogram QT interval.
AB  - No reports testing the efficacy of the use of the QT/RR ratio <1/2 for detecting
      a normal QTc interval were found in the literature. The objective of the present
      study was to determine if a QT/RR ratio < or =1/2 can be considered to be equal
      to the normal QTc and to compare the QT and QTc measured and calculated
      clinically and by a computerized electrocardiograph. Ratios (140 QT/RR) of 28
      successive electrocardiograms obtained from 28 consecutive patients in a tertiary
      level teaching hospital were analyzed clinically by 5 independent observers and
      by a computerized electrocardiograph. The QT/RR ratio provided 56% sensitivity
      and 78% specificity, with an area under the receiver operator characteristic
      curve of 75.8% (95%CI: 0.68 to 0.84). The divergence in QT and QTc interval
      measurements between clinical and computerized evaluation were 0.01 +/- 0.03 s
      (95%CI: 0.04-0.02) and 0.01 +/- 0.04 s (95%CI: -0.05-0.03), respectively. The QT
      and QTc values measured clinically and by a computerized electrocardiograph were
      similar. The QT/RR ratio < or =1/2 was not a satisfactory index for QTc
      evaluation because it could not predict a normal QTc value.

PMID- 14689041
TI  - Alternative parameters for echocardiographic assessment of fetal diastolic
      function.
AB  - Alternative methods to assess ventricular diastolic function in the fetus are
      proposed. Fetal myocardial hypertrophy in maternal diabetes was used as a model
      of decreased left ventricular compliance (LVC), and fetal respiratory movements
      as a model of increased LVC. Comparison of three groups of fetuses showed that,
      in 10 fetuses of diabetic mothers (FDM) with septal hypertrophy (SH), the mean
      excursion index of the septum primum (EISP) (ratio between the linear excursion
      of the flap valve and the left atrial diameter) was 0.36 +/- 0.09, in 8 FDM
      without SH it was 0.51 +/- 0.09 (P=0.001), and in the 8 normal control fetuses
      (NCF) it was 0.49 +/- 0.12 (P=0.003). In another study, 28 fetuses in apnea had a
      mean EISP of 0.39 +/- 0.05 which increased to 0.57 +/- 0.07 during respiration
      (P<0.001). These two studies showed that the mobility of the septum primum was
      reduced when LVC was decreased and was increased when LVC was enhanced. Mean
      pulmonary vein pulsatility was higher in 14 FDM (1.83 +/- 1.21) than in 26 NCF
      (1.02 +/- 0.31; P=0.02). In the same fetuses, mean left atrial shortening was
      decreased (0.40 +/- 0.11) in relation to NCF (0.51 +/- 0.09; P=0.011). These
      results suggest that FDM may have a higher preload than normal controls, probably
      as a result of increased myocardial mass and LV hypertrophy. Prenatal assessment
      of LV diastolic function by fetal echocardiography should include analysis of
      septum primum mobility, pulmonary vein pulsatility, and left atrial shortening.

PMID- 14689042
TI  - Presence of autoantibodies against HeLa small nuclear ribonucleoproteins in
      chagasic and non-chagasic cardiac patients.
AB  - We detected anti-human small nuclear ribonucleoprotein (snRNP) autoantibodies in
      chagasic patients by different immunological methods using HeLa snRNPs. ELISA
      with Trypanosoma cruzi total lysate antigen or HeLa human U small nuclear
      ribonucleoproteins (UsnRNPs) followed by incubation with sera from chronic
      chagasic and non-chagasic cardiac patients was used to screen and compare serum
      reactivity. Western blot analysis using a T. cruzi total cell extract was also
      performed in order to select some sera for Western blot and immunoprecipitation
      assays with HeLa nuclear extract. ELISA showed that 73 and 95% of chronic
      chagasic sera reacted with HeLa UsnRNPs and T. cruzi antigens, respectively. The
      Western blot assay demonstrated that non-chagasic cardiac sera reacted with high
      molecular weight proteins present in T. cruzi total extract, probably explaining
      the 31% reactivity found by ELISA. However, these sera reacted weakly with HeLa
      UsnRNPs, in contrast to the chagasic sera, which showed autoantibodies with human
      Sm (from Stefanie Smith, the first patient in whom this activity was identified)
      proteins (B/B', D1, D2, D3, E, F, and G UsnRNP). Immunoprecipitation reactions
      using HeLa nuclear extracts confirmed the reactivity of chagasic sera and human
      UsnRNA/RNPs, while the other sera reacted weakly only with U1snRNP. These
      findings agree with previously reported data, thus supporting the idea of the
      presence of autoimmune antibodies in chagasic patients. Interestingly, non
      chagasic cardiac sera also showed reactivity with T. cruzi antigen and HeLa
      UsnRNPs, which suggests that individuals with heart disease of unknown etiology
      may develop autoimmune antibodies at any time. The detection of UsnRNP
      autoantibodies in chagasic patients might contribute to our understanding of how
      they develop upon initial T. cruzi infection.

PMID- 14689043
TI  - Postprandial symptoms in dysmotility-like functional dyspepsia are not related to
      disturbances of gastric myoelectrical activity.
AB  - Gastric dysrhythmias, such as tachy- or bradygastria, have been reported in
      patients with functional dyspepsia (FD), but their role in symptom production is
      uncertain. It is also not known whether gastric dysrhythmias in these patients
      can be elicited by physiological gastric distension with a meal. We investigated
      the relationships between symptoms after ingestion of different volumes of water
      following a test meal and gastric dysrhythmias in FD patients. Fourteen patients
      with dysmotility-like FD and 13 healthy volunteers underwent paired
      electrogastrography (EGG) studies. Fasted subjects ingested 150 ml of yoghurt
      with either 150 ml (low volume) or 300 ml (high volume) water in random order.
      Fasting and fed EGGs with monitoring of symptoms were performed in both studies.
      Ten FD patients (71.4%) reported upper abdominal discomfort and bloating after
      the low volume meal, but only one (7.1%) presented an abnormal EGG (dominant
      frequency in the 2-4-cpm range: 58%). Following the high volume meal, 7 patients
      (50%) had symptoms, but none had EGG abnormalities. No significant differences
      were found between FD patients and controls for any of the EGG variables, in any
      test. In FD patients with postprandial symptoms, the percentage of the EGG
      dominant frequency in the normal range (median, 84.6%; range, 76.0-100.0%) was
      similar (P>0.20) to that in those without symptoms (88.5%; 75.0-100.0%). We
      conclude that disturbances of gastric myoelectrical activity are unlikely to play
      a role in the origin of postprandial upper abdominal discomfort and bloating in
      dysmotility-like FD.

PMID- 14689044
TI  - Prevalence of celiac disease in Brazilian children of short stature.
AB  - The aim of the present study was to determine the prevalence of celiac disease in
      children of short stature and to assess whether some of the routine laboratory
      examinations performed to determine the cause of short stature could suggest the
      presence of celiac disease. A total of 106 children of short stature and no
      gastrointestinal symptoms were studied. An extensive endocrine work-up had been
      negative for all of them and an additional investigation was performed by
      measuring the concentration of antiendomysial antibody. Patients who were
      positive for antiendomysial antibody (> or =1:10) or who exhibited IgA deficiency
      (less than 5 mg/dl) were referred for an endoscopic intestinal biopsy. We
      detected a pathological titer of antiendomysial IgA in six of these patients.
      Five of them showed histological abnormalities compatible with celiac disease and
      one had normal histology and was considered to have potential celiac disease. The
      prevalence of celiac disease in the population studied was 4.7% (with another
      0.9% of the subjects being considered to have potential celiac disease). The
      children with celiac disease did not differ in any of the parameters tested when
      compared to those without celiac disease, though they showed an improvement in
      growth velocity after treatment with a gluten-free diet. We conclude that it is
      important to test all children with short stature for celiac disease by measuring
      antiendomysial IgA.

PMID- 14689045
TI  - Impact of congenital calcitonin deficiency due to dysgenetic hypothyroidism on
      bone mineral density.
AB  - The objective of the present study was to determine the effect of chronic
      calcitonin deficiency on bone mass development. The results of 11 patients with
      thyroid dysgenesis (TD) were compared to those of 17 normal individuals (C) and
      of 9 patients with other forms of hypothyroidism (OH): 4 with hypothyroidism due
      to inborn errors of thyroid hormone synthesis and 5 with Hashimoto's thyroiditis.
      The subjects received an intravenous calcium stimulus and blood was collected for
      the determination of ionized calcium (Ca2+), calcitonin, and intact parathyroid
      hormone. Bone mineral density (BMD) was determined by dual-energy X-ray
      absorptiometry. After calcium administration the levels of Ca2+ in the two groups
      of hypothyroidism were significantly higher than in the normal control group (10
      min after starting calcium infusion: C=1.29 +/- 0.08 vs TD=1.34 +/- 0.03 vs
      OH=1.34 +/- 0.02 mmol/l; P<0.05), and only the TD group showed no calcitonin
      response (5 min after starting calcium infusion: C = 27.9 5.8 vs TD = 6.6 0.3 vs
      OH = 43.0 13.4 ng/l). BMD values did not differ significantly between groups (L2
      L4: C=1.116 +/- 0.02 vs TD=1.109 +/- 0.03 vs OH=1.050 +/- 0.04 g/cm2). These
      results indicate that early deficiency of calcitonin secretion has no detrimental
      effect on bone mass development. Furthermore, the increased calcitonin secretion
      observed in patients with inborn errors of thyroid hormone biosynthesis does not
      confer any advantage in terms of BMD.

PMID- 14689046
TI  - A comparison of public and private obstructive sleep apnea clinics.
AB  - The aim of the present study was to compare the clinical findings and
      polysomnography results obtained at public and private clinics in Brazil, the
      follow-up after diagnosis, and the therapeutic aspects related to continuous
      positive airway pressure. Patients who snore and who have obstructive sleep apnea
      were retrospectively divided into two groups, i.e., public clinic (N=307) and
      private clinic (N=317). Data concerning age, sex, body mass index (BMI), neck
      circumference, medical history, sleepiness scale, follow-up after diagnosis, and
      acceptance of continuous positive airway pressure therapy were collected. Mean
      age was 50 +/- 12 (range: 15-80) for public patients and 48 +/- 12 years (range:
      19-91) for private patients. Mean BMI was 30 +/- 6 (range: 19-67) for public
      patients and 31 +/- 6 kg/m (range: 21-59) for private patients. The public clinic
      had a significantly higher frequency of women than the private clinic (M:F ratio
      of 2.0:1 and 6.9:1, respectively). The condition of private patients (apnea
      hypopnea index=31 +/- 25) was more severe than that of public patients (apnea
      hypopnea index=25 +/- 24 events/h; P=0.0004). In the public and private clinics,
      19 and 15% of patients were snorers, respectively, and 81 and 85% of them had
      sleep apnea. After diagnosis, follow-up was longer in the private group. The
      continuous positive airway pressure acceptance was similar for both groups (32 vs
      35%), but patients from the public clinic abandoned treatment more than private
      ones (65 vs 13%). Social status was significant in terms of the severity of
      obstructive sleep apnea age and gender distribution. Private patients look for a
      diagnosis earlier in the course of the disease than public patients, adhere more
      to follow-up, and abandon continuous positive airway pressure treatment less than
      public patients do.

PMID- 14689047
TI  - Typing of Pseudomonas aeruginosa from hospitalized patients: a comparison of
      susceptibility and biochemical profiles with genotype.
AB  - Typing techniques are essential for understanding hospital epidemiology,
      permitting the elucidation of the source of infection and routes of bacterial
      transmission. Although DNA-based techniques are the "gold standard" for the
      epidemiological study of Pseudomonas aeruginosa, antibiotic profiles and
      biochemical results are used because they are easy to perform and to interpret
      and relatively inexpensive. Antibiotypes (susceptibility profiles) and biotypes
      (biochemical profiles) were compared to genotypes established by DNA restriction
      enzyme analysis in 81 clinical isolates of P. aeruginosa from three hospitals in
      Porto Alegre, Brazil. The epidemiological relationship among patients was also
      evaluated. Susceptibility and restriction profiles were discrepant in more than
      50% of the cases, and many antibiotypes were observed among isolates from the
      same genotype. Furthermore, susceptibility profiles did not allow the distinction
      of isolates from unrelated genotypes. Since a large number of isolates (63%)
      yielded the same biochemical results, only 10 biotypes were detected, showing
      that this typing method has a low discriminatory power. On the other hand, DNA
      restriction enzyme typing allowed us to establish 71 distinct types.
      Epidemiological data about the relation among P. aeruginosa isolates were not
      conclusive. The results of the present study indicate that the only method that
      can establish a clonal relation is DNA restriction enzyme typing, whereas the
      other methods may cause misleading interpretations and are inadequate to guide
      proper infection control measures.

PMID- 14689048
TI  - Estrogen and progesterone receptors in human papilloma virus-related cervical
      neoplasia.
AB  - Estrogen (ER) and progesterone (PR) receptors in the normal uterine cervix,
      cervical intraepithelial neoplasia and invasive carcinoma were studied in
      consecutive samples from Hospital do Cancer, Sao Paulo, between 1996 and 1997.
      Tissue was collected by removing a fragment of the tumoral area using a 5-mm
      diameter biopsy punch, followed by removal of a macroscopically normal area as
      close as possible from the tumor. Histopathological confirmation was obtained for
      all specimens analyzed. A total of 24 normal tissues, 17 cases of cervical
      intraepithelial neoplasia and 7 of invasive carcinomas were studied. The ER/PR
      ratio was determined by immunohistochemistry using monoclonal antibodies specific
      for each receptor. Adjacent tissue slides were submitted to generic PCR for human
      papillomavirus (HPV) DNA detection followed by typing by dot blot hybridization.
      About half (45.8%) of the tumors were HPV DNA positive while 29.1% of the
      patients were also HPV positive in their respective normal tissue. ER was
      negative in the tumoral epithelium of 11 HPV-positive patients (P=0.04). There
      was a trend in the ER distribution in normal tissue that was opposite to that
      from lesions, but it was not statistically significant (P=0.069). No difference
      in ER distribution in stromal tissues was observed between HPV-positive and HPV
      negative tissues. PR staining was negative in the epithelium of all cases
      studied. The results obtained from this small number of cases cannot be
      considered to be conclusive but do suggest that factors related to viral
      infection affect the expression of these ER/PR cervix receptors.

PMID- 14689049
TI  - Does the correlation between EBNA-1 and p63 expression in breast carcinomas
      provide a clue to tumorigenesis in Epstein-Barr virus-related breast
      malignancies?
AB  - Several investigators have identified Epstein-Barr virus (EBV) particles in
      breast carcinomas, a fact that supports a role for EBV in mammary tumorigenesis.
      The possible mechanism involved in this process is not clear. The present study
      was carried out in an attempt to determine whether there is a relationship
      between latent infection with EBV and p53 and p63 expression in breast
      carcinomas. Immunohistochemistry developed with 3.3-diaminobenzidine
      tetrahydrochloride was performed in 85 formalin-fixed paraffin-embedded breast
      carcinomas using anti-EBV EBNA-1, anti-p63, anti-p53, anti-estrogen receptor (ER)
      and anti-progesterone receptor (PR) antibodies. The cases were selected to
      represent each of the various histologic types: intraductal carcinoma (N=12),
      grade I invasive ductal carcinoma (N=15), grade II invasive ductal carcinoma
      (N=15), grade III invasive ductal carcinoma (N=15), tubular carcinoma (N=8),
      lobular carcinoma (N=10), and medullary carcinoma (N=10). The ductal breast
      carcinomas were graded I, II and III based on the Scarff-Bloom and Richardson
      grading system modified by Elston and Ellis. One slide containing at least 1000
      neoplastic cells was examined in each case. ER, PR, p63, p53 and EBNA-1 were
      positive in 60, 40, 11.8, 21.2 and 37.6% of carcinomas, respectively. There was a
      correlation between EBNA-1 and p63 expression (P<0.001), but not between EBNA-1
      and p53 (P=0.10). These data suggest a possible role for p63 in the mammary
      tumorigenesis associated with Epstein-Barr virus infection.

PMID- 14689050
TI  - Topographic abnormality of slow cortical potentials in schizophrenia.
AB  - A recent study from our laboratory has provided evidence for the generation of
      slow potentials occurring in anticipation to task-performance feedback stimuli,
      in multiple association cortical areas, consistently including two prefrontal
      areas. In the present study, we intended to determine whether these slow
      potentials would indicate some abnormality (topographic) in schizophrenic
      patients, and thus serve as an indication of abnormal association cortex
      activity. We recorded slow potentials while subjects performed a paired
      associates memory task. A 123-channel EEG montage and common average reference
      were used for 20 unmedicated schizophrenic (mean duration of illness: 11.3 +/-
      9.2 years; mean number of previous hospitalizations: 1.2 +/- 1.9) and 22 healthy
      control subjects during a visual paired-associates matching task. For the
      topographic analysis, we used a simple index of individual topographic deviation
      from normality, corrected for absolute potential intensities. Slow potentials
      were observed in all subjects. Control subjects showed a simple spatial pattern
      of voltage extrema (left central positive and right prefrontal negative), whereas
      schizophrenic patients presented a more complex, fragmented pattern. Topographic
      deviation was significantly different between groups (P<0.001). The increased
      topographic complexity in schizophrenics could be visualized in grand averages
      computed across subjects. Increased topographic complexity could also be seen
      when grand averages were computed for subgroups of patients assembled either
      according to task-performance (high versus low) or by their scores on
      psychopathological scales. There was no significant correlation between
      topographic deviation and psychopathology scores. We conclude that the slow
      potential topographic abnormalities of schizophrenia indicate an abnormality in
      the configuration of large-scale electrical activity in association cortices.

PMID- 14689051
TI  - Measurement of epidermal thickness in a patient with psoriasis by computer
      supported image analysis.
AB  - The aim of the present study was to measure full epidermal thickness, stratum
      corneum thickness, rete length, dermal papilla widening and suprapapillary
      epidermal thickness in psoriasis patients using a light microscope and computer
      supported image analysis. The data obtained were analyzed in terms of patient
      age, type of psoriasis, total body surface area involvement, scalp and nail
      involvement, duration of psoriasis, and family history of the disease. The study
      was conducted on 64 patients and 57 controls whose skin biopsies were examined by
      light microscopy. The acquired microscopic images were transferred to a computer
      and measurements were made using image analysis. The skin biopsies, taken from
      different body areas, were examined for different parameters such as epidermal,
      corneal and suprapapillary epidermal thickness. The most prominent increase in
      thickness was detected in the palmar region. Corneal thickness was more
      pronounced in patients with scalp involvement than in patients without scalp
      involvement (t=-2.651, P=0.008). The most prominent increase in rete length was
      observed in the knees (median: 491 microm, t=10.117, P=0.000). The difference in
      rete length between patients with a positive and a negative family history was
      significant (t=-3.334, P=0.03), being 27% greater in psoriasis patients without a
      family history. The differences in dermal papilla distances among patients were
      very small. We conclude that microscope-supported thickness measurements provide
      objective results.

PMID- 14689052
TI  - Cardiovascular complications and increased levels of circulating modified low
      density lipoprotein in HIV patients and patients with lipodystrophy.
AB  - The introduction of highly active antiretroviral therapy (HAART) for patients
      infected with HIV has significantly prolonged the life expectancy and to some
      extent has restored a functional immune response. However, the premature
      introduction of HAART has led to a significant and alarming increase in
      cardiovascular complications, including myocardial infarction and the appearance
      of abnormal distribution of body fat seen as lipodystrophy. One key element in
      the development of ischemic coronary artery disease is the presence of
      circulating and tissue-fixed modified low density lipoprotein (mLDL) that
      contributes to the initiation and progression of arterial lesions and to the
      formation of foam cells. Even though not completely elucidated, the most likely
      mechanism involves mLDL in the inflammatory response and the induction of a
      specific immune response against mLDL. Circulating antibodies against mLDL can
      serve as an indirect marker of the presence of circulating and vessel-fixed mLDL.
      In the present study, we measured antibodies to mLDL and correlated them with
      immune status (i.e., number of CD4+ T cells) in 59 HIV patients and with the
      clinical manifestation of lipodystrophy in 10 patients. We observed a significant
      reduction in anti-mLDL antibody levels related both to lipodystrophy and to an
      immunocompromised state in HIV patients. We speculate that these antibodies may
      explain in part the rapid development of ischemic coronary artery disease in some
      patients.

PMID- 14689053
TI  - Prevalence of antibodies to human herpesvirus-8 in populations with and without
      risk for infection in Sao Paulo State.
AB  - Human herpesvirus 8 (HHV-8) is a newly described herpesvirus that is
      etiologically associated with all forms of Kaposi's sarcoma (KS).
      Seroepidemiological studies have shown high prevalence rates of HHV-8 antibodies
      among men who have sex with men (MSM) and AIDS patients, African children,
      Brazilian Amerindians, and elderly individuals in certain regions of Europe. The
      aim of the present study was to determine the prevalence of HHV-8 antibodies in
      healthy children and young adults from different cities in Sao Paulo State, and
      in a population at high risk for HHV-8 infection: HIV-negative MSM, and AIDS
      patients with and without KS. Antibodies to HHV-8 latency-associated nuclear
      antigen and lytic-phase antigens were detected by immunofluorescence assays. In
      643 healthy children and young adults from the general population attending a
      vaccination program for yellow fever in ten different cities in Sao Paulo State,
      the prevalence of HHV-8 antibodies detected by the presence of latent or lytic
      antigens ranged from 1.0 to 4.1% in the different age groups (mean=2.5%). In the
      MSM group, the prevalence was 31/95 (32.6%). In the group of patients with AIDS,
      the prevalence was 39.2% (51/130) for non-KS patients and 98.7% (77/78) for AIDS
      patients with the diagnosis of KS confirmed by histopathological examination. We
      conclude that HHV-8 has a restricted circulation among healthy children and young
      adults in the general population of Sao Paulo State and a high prevalence among
      MSM and AIDS patients.

PMID- 14689054
TI  - Serum cytokine profile in the subclinical form of visceral leishmaniasis.
AB  - The factors determining the development or not of visceral leishmaniasis (VL)
      have not been completely identified, but a Leishmania-specific cellular immune
      response seems to play a fundamental role in the final control of infection. Few
      studies are available regarding the production of cytokines in the subclinical
      form of VL, with only the production of IFN-gamma and TNF-alpha known. The aim of
      the present study was to identify immunological markers for the oligosymptomatic
      or subclinical form of VL. A prospective cohort study was conducted on 784
      children aged 0 to 5 years from an endemic area in the State of Maranhao, Brazil,
      between January 1998 and December 2001. During 30 consecutive months of follow
      up, 33 children developed the oligosymptomatic form of the disease and 12 the
      acute form. During the clinical manifestations, serum cytokine levels were
      determined in 27 oligosymptomatic children and in nine patients with the acute
      form using a quantitative sandwich enzyme immunoassay. In the subclinical form of
      VL, variable levels of IL-2 were detected in 52.3% of the children, IL-12 in
      85.2%, IFN-gamma in 48.1%, IL-10 in 88.9%, and TNF-alpha in 100.0%, with the last
      two cytokines showing significantly lower levels than in the acute form. IL-4 was
      not detected in oligosymptomatic individuals. Multiple discriminant analysis used
      to determine the profile or combination of cytokines predominating in the
      subclinical form revealed both a Leishmania resistance (Th1) and susceptibility
      (Th2) profile. The detection of both Th1 and Th2 cytokine profiles explains the
      self-limited evolution accompanied by the discrete alterations observed for the
      subclinical form of VL.

PMID- 14689055
TI  - Clinical and molecular analysis of human reproductive disorders in Brazilian
      patients.
AB  - Several genes that influence the development and function of the hypothalamic
      pituitary-gonadal-axis (HPG) have been identified. These genes encode an array of
      transcription factors, matrix proteins, hormones, receptors, and enzymes that are
      expressed at multiple levels of the HPG. We report the experience of a single
      Endocrinology Unit in the identification and characterization of naturally
      occurring mutations in families affected by HPG disorders, including forms of
      precocious puberty, hypogonadism and abnormal sexual development due to impaired
      gonadotropin function. Eight distinct genes implicated in HPG function were
      studied: KAL, SF1, DAX1, GnRH, GnRHR, FSHbeta, FSHR, and LHR. Most mutations
      identified in our cohort are described for the first time in literature. New
      mutations in SF1, DAX1 and GnRHR genes were identified in three Brazilian
      patients with hypogonadism. Eight boys with luteinizing hormone- (LH) independent
      precocious puberty due to testotoxicosis were studied, and all have their LH
      receptor (LHR) defects elucidated. Among the identified LHR molecular defects,
      three were new activating mutations. In addition, these mutations were frequently
      associated with new clinical and hormonal aspects, contributing significantly to
      the knowledge of the molecular basis of reproductive disorders. In conclusion,
      the naturally occurring genetic mutations described in the Brazilian families
      studied provide important insights into the regulation of the HPG.

PMID- 14689056
TI  - Mutations in the SRY, DAX1, SF1 and WNT4 genes in Brazilian sex-reversed
      patients.
AB  - In most mammals, male development is triggered by the transient expression of the
      SRY gene, which initiates a cascade of gene interactions ultimately leading to
      the formation of a testis from the indifferent fetal gonad. Mutation studies have
      identified several genes essential for early gonadal development. We report here
      a molecular study of the SRY, DAX1, SF1 and WNT4 genes, mainly involved in sexual
      determination, in Brazilian 46,XX and 46,XY sex-reversed patients. The group of
      46,XX sex-reversed patients consisted of thirteen 46,XX true hermaphrodites and
      four 46,XX males, and was examined for the presence of the SRY gene and for the
      loss of function (inactivating mutations and deletions) of DAX1 and WNT4 genes.
      In the second group consisting of thirty-three 46,XY sex-reversed patients we
      investigated the presence of inactivating mutations in the SRY and SF1 genes as
      well as the overexpression (duplication) of the DAX1 and WNT4 genes. The SRY gene
      was present in two 46,XX male patients and in none of the true hermaphrodites.
      Only one mutation, located outside homeobox domain of the 5' region of the HMG
      box of SRY (S18N), was identified in a patient with 46,XY sex reversal. A novel 8
      bp microdeletion of the SF1 gene was identified in a 46,XY sex-reversed patient
      without adrenal insufficiency. The dosage of DAX1 and WNT4 was normal in the sex
      reversed patients studied. We conclude that these genes are rarely involved in
      the etiology of male gonadal development in sex-reversed patients, a fact
      suggesting the presence of other genes in the sex determination cascade.

PMID- 14689057
TI  - Reimmunization after bone marrow transplantation--current recommendations and
      perspectives.
AB  - Autologous and allogeneic bone marrow transplantation (BMT) recipients lose
      immune memory of exposure to infectious agents and vaccines accumulated through a
      lifetime and therefore need to be revaccinated. Diphtheria toxoid, tetanus
      toxoid, pertussis vaccine (children <7 years old), Haemophilus influenzae type b
      conjugate, 23-valent pneumococcal polysaccharide, inactivated influenza vaccine,
      inactivated polio vaccine and live-attenuated measles-mumps-rubella vaccine are
      the currently recommended vaccines to be included in a vaccination program after
      BMT. For most of them, the best time to vaccinate, the number of vaccine doses
      and/or the duration of immunity after vaccination have not been established.
      Vaccination protocols vary greatly among BMT centers, suggesting that the lack of
      sufficient data has not permitted the formulation of reliable recommendations.
      The use of other vaccines and the perspectives for different vaccination
      protocols are analyzed in this review.

PMID- 14689058
TI  - Involvement of the nucleotide excision repair proteins in the removal of
      oxidative DNA base damage in mammalian cells.
AB  - Oxidative DNA base damage produced primarily by reactive oxygen species is
      assumed to be the most important endogenous damage. Lack of its repair may
      contribute to mutagenesis, carcinogenesis and aging. It is supposed that most
      oxidative DNA base damage is removed by the base excision repair pathway;
      although it was shown recently that other DNA repair pathways could be involved.
      This review is focused on the role of nucleotide excision repair (NER) and
      transcription-coupled repair (TCR) in the removal of oxidative DNA base damage in
      mammalian cells.

PMID- 14689059
TI  - Paget's disease of the nipple: a copy number of the genes ERBB2 and CCND1 versus
      expression of the proteins ERBB-2 and cyclin D1.
AB  - Paget's disease of the nipple (PDN) is characterized by Paget's cells
      infiltrating from an underlying breast carcinoma into the epidermis of the
      nipple. The tumor cells were reported to overexpress ERBB-2 protein. There is no
      evidence, whether the overexpression is caused by amplification of the ERBB2 gene
      (as is the case of invasive duct carcinomas) or by other causes. Because the
      Paget's cells proliferate vividly we were interested also in cyclin D1 expression
      and in its relation to the number of CCND1 gene copies. To address these issues,
      we performed a study using fluorescence in situ hybridization on interphasic
      nuclei (I-FISH) on formalin fixed / paraffin embedded tissue sections from twelve
      women with PDN. We compared immunohistochemical (IHC) expression of the ERBB-2
      protein and cyclin D1 with the copy number of the gene ERBB2 and CCND1,
      respectively (I-FISH). In all cases of our series we found overexpression of the
      ERBB-2 protein (3+), and in all of them there was a strong amplification of the
      ERBB2 gene (more than 10 signals per a nucleus, usually about 20). Keratinocytes
      of the epidermis had two signals of the gene. IHC and I-FISH revealed comparable
      findings in successive biopsies in two patients. Cyclin D1 was positive in seven
      cases. We found a moderate amplification of the CCND1 gene (up to 10 signals per
      a nucleus) in three patients only. Any correlation between the cyclin D1
      overexpression anda copy number of the CCND1 gene was observed. Combined
      numerical changes of chromosome 17 and of chromosome 11 were found in seven
      women. It is concluded that in PDN, the ERBB-2 protein overexpression is caused
      by amplification of the ERBB2 gene. A specific immuno-therapy with trastuzumab
      (Herceptin) used in patients with invasive duct carcinoma may be also effective
      in patients with PDN.

PMID- 14689060
TI  - The novel exon 11 mutation of BRCA1 gene in a high-risk family.
AB  - Germline mutations in the BRCA1 and BRCA2 genes are required for the initiation
      of the development of hereditary forms of breast and ovarian cancer, which
      represent 10-15% of all cases. The course of the disease varies from case to case
      that can be due even to the possibility of multiple genetic changes including
      inactivation of other tumor suppressor genes--TP53 and APC genes or activation of
      oncogenes, especially K-ras oncogene. The combination of these changes results in
      an early expression of the broad variety of malignancies. The analyzed proband
      (II-5) comes from a high-risk family, in which various types of cancer were
      observed. The novel BRCA1 mutation in exon 11 (2057delCAGTGAAGAG) was detected by
      SSCP, HDA techniques and confirmed by automatic sequencing. The same deletion was
      observed in DNA sample of her first daughter (III-1), but DNA of her second one
      was without any mutational changes (III-2). Due to the occurrence of different
      types of cancer in this family, the incidental mutations in the APC; resp. TP53
      tumor supressor genes and K-ras oncogene were searched as well. Any mutation was
      found after sequencing of SSCP interesting exons of these genes. The reasons for
      such strong malignant manifestation in this high risk family are discussed.

PMID- 14689061
TI  - Argyrophilic nucleolar organizer regions (AgNORs) in relation to p53 and bcl-2
      protein expression in leukemia patients.
AB  - The aim of this study was to assess the possible relationship between the silver
      stained nucleolar organizer regions (AgNOR) and immunocytochemically detected p53
      and bcl-2 proteins in ALL, AML, B-CLL and CML patients (adults and children) at
      the initial presentation. AgNORs are loops of DNA, correlated with proliferative
      potential of cells. Alteration in p53 and bcl-2 proteins expression may
      characterize the malignant potential of leukemic cells. The patients were
      subdivided according to the p53 positivity and negativity. The frequency of p53
      positive patients was relatively low in T-ALL (29%) and B-CLL (16%). B-ALL, AML
      and CML patients revealed higher frequency of p53 protein (46%, 47% and 88%,
      respectively). The overall frequency of positive cytoplasmic staining for bcl-2
      protein was demonstrated in the majority of patients. No significant differences
      in the percentage of p53-positive cells among leukemia subtypes were seen. The
      proportion of bcl-2 protein positive cells did not differ significantly among
      various leukemia subtypes, except for significant differences between p53
      positive and p53-negative peripheral blood (p=0.0073) and bone marrow (p=0.0175)
      cells of B-CLL patients. The samples from healthy subjects used as controls
      exhibited relatively low numbers of AgNOR dots in both, peripheral blood and bone
      marrow cells. Highly significant differences in AgNOR quantities between healthy
      donors and p53 protein positive peripheral blood as well as bone marrow cells of
      distinct leukemia subtypes (except for bone marrow cells in B-CLL patients,
      p=0.1727) were observed. Significant differences in AgNOR count between p53
      protein positive and p53 protein negative samples of peripheral blood cells of B
      ALL (p=0.0099) as well as B-CLL (p=0.0117) cases were found. No significant
      differences (except for B-CLL, p=0.0558) were encountered in bone marrow cells.
      P53 protein positivity or negativity did not influence the amount of AgNOR
      proteins in cells of our T-ALL and AML cases. Mutual comparing the number of
      AgNOR dots among different leukemias showed that for both peripheral blood and
      bone marrow cells the differences between ALL and AML (p=0.0383 and p=0.0033,
      respectively) as well as for peripheral blood of AML and CML (p=0.0302) were
      statistically significant. The bcl-2 protein positivity did not affect
      significantly the AgNOR distribution either in p53 protein positive or p53
      negative cases of our leukemia patients. However, an association between the
      lowest AgNOR quantity and highest bcl-2 protein expression in p53-negative B-CLL
      patients was seen for both peripheral blood and bone marrow cells. The
      correlation between relatively high AgNOR numbers and relatively increased
      percentage of bcl-2 protein in the p53-positive cases of CML patients was found
      in some cases. Regarding the age and sex, the AgNOR distribution in p53-positive
      and p53-negative leukemia cases in children and adults showed neither
      relationship nor dependence. The WBC count differed evidently among distinct
      leukemia subtypes, with enormous heterogeneity in range as well. Larger studies
      are needed in order to consolidate these preliminary results and characterize the
      possible prognostic value of AgNOR in association with p53 and bcl-2 proteins
      expression.

PMID- 14689062
TI  - Multiparametric flow cytometry in detection of minimal residual disease in acute
      lymphoblastic leukemia of early B-cell phenotype.
AB  - Leukemic cells can be distinguished from normal hematopoietic cells on the basis
      of chromosomal or molecular abnormalities, antigen receptor gene rearrangements
      and immunophenotype. Set of 3-, 4-combination of monoclonal antibodies was used
      for exact definition of immunophenotypic characteristics of B-cells populations
      from healthy donors and aberrant, asynchronous, over/under-expressed phenotypes
      and detection changes in intensity expression of markers that characterized
      pathological leukemic B-cells at diagnosis. These differences in normal and
      abnormal cell patterns were very important and could be utilized for analysis of
      minimal residual disease. On the basis of these findings we were able to clearly
      distinguish residual leukemic cells from hematogones (healthy B-lymphocyte
      precursors) too. We also verified that in some cases the CD58 marker is
      overexpressed on CD10+, CD34+ blast cells at diagnosis and can be feasible used
      for detection of minimal residual disease (MRD).

PMID- 14689063
TI  - Leukemic cells and aberrant phenotypes in acute leukemia patients: a flow
      cytometry analysis.
AB  - The aim of this study was to evaluate the heterogeneity of immunophenotype
      features in acute leukemia patients and to detect the presence of leukemia
      associated immunophenotypes. We prospectively investigated the phenotype of blast
      cells from 44 adult acute leukemia patients using a large panel of monoclonal
      antibodies by multiparametric flow cytometry. Thirty-three patients were
      classified as AML according to the FAB classification. Eleven patients were
      diagnosed as ALL (10 cases B-ALL, 1 case T-ALL) according to both FAB and
      immunnophenotyping. We found leukemia-associated phenotypes in 28 of 33 AML
      patients (84.8%) and in 8 of 11 ALL patients (72.7%). In 61.1% of patients more
      than one aberrant phenotype was observed. Linear infidelity was the most frequent
      aberrancy in both AML (64.3%) and ALL (37.5%) subgroups. The present study shows
      that MFC is a helpful method for sufficient identification of leukemic cells and
      for determination of blast cells immunophenotype heterogeneity. The double stain
      flow cytometry in our study revealed aberrant phenotypes in up to 81.8% patients.

PMID- 14689064
TI  - NMU-induced mammary carcinogenesis in female rats is influenced by repeated
      psychoemotional stress.
AB  - Epidemiological and experimental studies indicate psychoemotional stress as an
      important factor in carcinogenesis. The aim of this study was to evaluate the
      effect of restraint stress on N-nitroso-N-methylurea (NMU)-induced mammary
      carcinogenesis. Female Sprague-Dawley rats were injected with two intraperitoneal
      NMU doses each per 50 mg/kg b.w. between 39-49 postnatal days. Three experimental
      groups were created: 1. NMU (without restraint--control group, 12 animals), 2.
      NMU+1IMS (group with single restraint, IMS--immobilization stress, 12 animals),
      3. NMU+7IMS (group restrained 7 times during a week, 12 animals). Animals were
      immobilized daily in special boxes for 120 minutes or 7 x 120 minutes,
      respectively from third day after carcinogen administration. The observation
      lasted for 20 weeks. The incidence, frequency, latency and volume of mammary
      tumors were evaluated. In repeatedly immobilized group NMU+7IMS increase in tumor
      incidence by 57% (p<0.05), marked increase in frequency per group by 153%
      (p<0.01), increase in frequency per animal by 61% and shortened latency period by
      7 days were recorded. The effect of single restraint was not seen. In this
      experiment repeated immobilization carried out early after carcinogen
      administration had a remarkable stimulatory effect on chemically-induced mammary
      carcinogenesis in female rats.

PMID- 14689065
TI  - Fludarabine combined with cyclophosphamid is highly effective in the treatment of
      chronic lymphocytic leukemia.
AB  - Combined treatment of fludarabine (FLU) with cyclophosphamide (CY) may increase
      the complete remission (CR) rate, decreased minimal residual disease (MRD) and,
      possibly, prolong survival in B-chronic lymphocytic leukemia patient's (B-CLL).
      The aim of study was to evaluate the activity and toxicity of FLU in combination
      with CY, the FLU-CY schedule, in patients with previously untreated B-CLL. From
      May 1999 to December 2002, 57 patients with advanced or progressive B-CLL
      received treatment with FLU at a dose of 30 mg/m2 for three consecutive days and
      CY at a dose of 300 mg/m2 for three days. The cycles were repeated at four week
      intervals or longer if severe myelosupression occurred. Guidelines for the
      evalution of response and toxicity were those developed by the National Cancer
      Institute Sponsored Working Group. Minimal residual disease (MRD) was detected by
      immunophenotyping only in patients with CR by standard criteria. In the analyzed
      group an overall response (OR) rate (CR+PR) of 89.5% (95% CI 80.6-94.7%) was
      achieved, including complete response in 29.8%. At the time of analysis 15 of 17
      patients with CR are still in remission. Median duration of follow up in these is
      12 (range 4-29.2) months. MRD was detected only in five out of 17(29.4%) patients
      with CR. Grade III/IV thrombocytopenia was seen in 3 (5.2%) patients and grade
      III/IV neutropenia in 6 (10.5%). Severe infections were noted in 14 (24%)
      patients. Two (3.5%) patients died, one due to sepsis, one as a result of disease
      progression. The FLU-CY regimen is highly effective combination in previously
      untreated CLL patients with acceptable toxicity. The efficacy of the regimen
      seems to be higher than that observed earlier after treatment with FLU alone.

PMID- 14689066
TI  - The clinical characteristics and the role of surgery and imatinib treatment in
      patients with liver metastases from c-Kit positive gastrointestinal stromal
      tumors (GIST).
AB  - The purpose of this study was to analyze the clinical features of the group of c
      KIT positive GIST patients with liver metastases evaluated and treated in two
      referral institutions as well as to attempt to define the role of surgery in the
      management of GIST given the emergence to imatinib as an important part of
      treatment strategy in GIST patients. Between August 2001 and December 2002, 90
      patients with c-KIT positive GIST were referred to our institutions. In 50
      patients metastatic disease were disclosed. Of these, 35 patients (35/50; 70%)
      were rendered to have liver metastases and therefore offered imatinib or surgical
      therapy depend on CT assessment. The median follow-up of these 35 patients
      calculated from the time of first operation was 23 months (range 3-246 months).
      Male patients comprised the majority of patients (70%) with liver metastases. In
      14 patients (40%) the metastases were confined only to the liver, in the others
      21 patients (60%) the liver metastases were accompanied by intraperitoneal
      dissemination (17; 48.6%) or local recurrences (4; 11.4%). The period of time
      between the diagnosis of primary lesion and occurring liver metastases ranged
      from 0 to 164 months (median time of liver metastases presentation was 16 months
      for patients undergone primary curative surgery). The liver metastases were
      estimated as resectable in 3 cases (8.6%) and hepatic resection of all gross
      lesions was possible. Group of 32 patients with unresectable liver involvement
      was considered to treatment with imatinib. The median time of imatinib treatment
      for survivors is 7.5 months (range: 3.5-18.5 months). Twelve patients (37.5%)
      demonstrated partial response (PR) and 16 patients (50%) stable disease (SD)
      according to RECIST criteria. We did not observe any complete response (CR). At
      median follow-up 7 months, 32 of 35 patients (91.4%) were alive, 3 patients
      (8.6%)remained free of disease and 28 patients (87.5%) remained on imatinib
      treatment and have maintained disease although with partial response or
      stabilization only. Radical surgical resection remains the only possibility of
      cure for GIST patients because the complete response after imatinib therapy is
      restricted to a few patients only. However, despite the advanced metastatic
      disease, approximately 90% of patients are alive and continue imatinib treatment
      with median follow-up time more than 7 months. Surgery in combination with
      adjuvant imatinib treatment may result in improved survival with patients with
      advanced GIST.

PMID- 14689067
TI  - Effects of flavonoids on glutathione and glutathione-related enzymes in cisplatin
      treated L1210 leukemia cells.
AB  - Connections between the ability of quercetin (Qu)and galangin (Ga) to
      differentially modulate cis-Pt-induced apoptosis and their effects on glutathione
      system of murine L1210 leukemia cells were studied. The results showed that total
      glutathione (GSHt) level is increased significantly (cca 123% of control level),
      both in cells treated with 10 microM Qu and in cells treated with 4 microM cis-Pt
      and 10 microM Qu in combination. 10 microM Ga had no effect on GSHt content.
      Activities of glutathione S-transferase (GST) and glutathione reductase (GR) were
      not changed significantly when 10 microM flavonoids were used. Significant
      inhibition of GR activity was observed when flavonoids were used in
      concentrations higher than 25 microM. The presented data indicate that Qu change
      the redox state of the cells that is implicated in regulation of apoptosis, due
      to its ability to increase the GSHt level, and thus may potentiate cis-Pt-induced
      apoptosis of L1210 cells.

PMID- 14689068
TI  - Serum thrombopoietin levels in patients with reactive thrombocytosis due to lung
      cancer and in patients with essential thrombocythemia.
AB  - In patients with thrombocytosis normal to increased serum thrombopoietin (TPO)
      levels have been reported. The aim of this study was to investigate the
      relationship between serum TPO concentration, platelet number and plasma levels
      of fibrinogen in patients with reactive thrombocytosis (RT) due to lung cancer
      and in patients with essential (primary) thrombocythemia (ET). A total of 70
      newly diagnosed patients with RT or ET (platelet counts >600 G/l) were studied:
      45 with RT due to lung cancer (25 with non-small cell lung cancer, NSCLC and 20
      with small cell lung cancer, SCLC), and 25 with ET. Twenty normal volunteers were
      used as controls. TPO was measured by immunoassay technique (ELISA). Mean serum
      TPO values in patients with RT due to lung cancer were statistically
      significantly higher than those in patients with ET or in controls. The highest
      platelet count was seen in patients with ET, and mean plasma fibrinogen levels
      were the highest in RT patients. In NSCLC patients mean serum TPO concentrations
      were higher (not statistically significant) than in SCLC, and a statistically
      significant relationship between TPO serum concentration and fibrinogen level was
      observed. No correlations between platelet counts and TPO serum concentrations
      were found. Our results indicate increased serum TPO levels in patients with
      thrombocytosis in lung cancer which may be related to the activity of neoplasms.
      In addition, it is postulated that the relatively low TPO values in patients with
      ET may result from a dysregulation of the feedback loop involved in platelet
      production.

PMID- 14689069
TI  - Hemoglobin as a factor influencing the outcome in inoperable oropharyngeal
      carcinoma treated by concomitant radiochemotherapy.
AB  - The aim of the study was to analyze the prognostic significance of hemoglobin
      (Hb) concentration for loco-regional control and survival of patients with
      inoperable carcinoma of the oropharynx. Seventy patients with inoperable squamous
      cell carcinoma of the oropharynx were prospectively treated by concomitant
      regimen of conventional radiotherapy and chemotherapy with Mitomycin C and
      Bleomycin. The prognostic value of Hb concentration before the therapy (Hb-S) and
      at the end of the therapy (Hb-E), the difference between both (DHb), and the
      average Hb concentration (Hb-Av) were analyzed. Hb concentration was falling
      significantly (median values, from 139 g/L to p<0.0001) during the first three
      weeks of the therapy; after that, it reached a plateau. In the last week of
      therapy, a slight increase (p=0.08) in Hb concentration was recorded. Significant
      correlation (p<0.0001) was found between Hb-S and other Hb-related parameters.
      The median follow-up of the patients alive on close-out date was 5.7 years (range
      4-10.5 years). Longer disease-free survival (DFS) and disease-specific survival
      (DSS) correlated with higher values of Hb-S (p=0.0005, p=0.008) and Hb-E (p=0.02,
      p=0.02), while the Hb-Av was predictive for DFS only (p=0.004). The most
      significant difference between low- and high-Hb groups was calculated at cut-off
      concentrations of 122 (Hb-S), 116 (Hb-E), and 120 (Hb-Av) g/L. Only Hb-S was
      tested in multi- variate model where its independent value for predicting both,
      DFS (p=0.002; RR 3.6) and DSS (p=0.01; RR 2.9), was confirmed. In our patients,
      Hb-Swas proved to bean independent prognostic factor in predicting DFS and DSS.
      We believe that the concentration of Hb > or =120 g/L should be maintained during
      radiotherapy course.

PMID- 14689070
TI  - Lens-sparing external beam radiotherapy of intraocular metastases: our
      experiences with twenty four eyes.
AB  - Occurrence of uveal metastases is higher, than the number of clinically diagnosed
      cases, furthermore all cases are not amenable to therapy. Treatment of primary
      cancer is permanently improving, as a result life prospective is better, with an
      increasing number of late distant metastases in an unusual location, as e.g.
      intraocular metastasis. As surgical approach is not suitable, and chemo/hormonal
      therapy often has a limited effect on intraocular dissemination, other treatment
      modalities are needed for the maintenance of visual acuity, and prevention of
      further deterioration of the quality of life. The study was made to evaluate the
      efficacy of external beam radiotherapy (EBRT) with lens-sparing techniques in the
      management of patients developing intraocular metastases (IOM). Between March
      1994 and March 2002, 24 eyes of 17 patients with tumors metastatic to the eye
      were treated by EBRT. The female:male ratio was 8.5:1, age ranged between 37 and
      74 years (mean: 56 years). The site of the primary tumor was: breast (11), lung
      (4) and others (2). The visual acuity at the beginning of irradiation was between
      0.1-0.7 (mean 0.5) and a mean KPS of 60% was detected. The mean time elapsed from
      the diagnosis of primary tumor and recognition of metastasis was 38.9 months in
      case of breast, and 6.7 months in lung cancer. Eyes were treated by 6 MV photon
      beams, using a modified technique of Schipper's lens-sparing retinoblastoma
      treatment method. The following parameters were studied: visual acuity changes,
      local response rate, survival times from irradiation and ocular complications.
      Mean follow-up time was 24 months. Mean visual acuity improved two lines on the
      Snellen chart. The mean survival time after treatment of IOM was 21 months in
      breast and 4.9 months in lung cancer patients. Local response rate was 78%. No
      radiation cataract was observed. Only one patient developed radiation retinopathy
      32 months after the treatment. External beam radiotherapy is recommended for the
      treatment of intraocular metastases to improve quality of life. In selected cases
      -especially breast cancer patients--lens-sparing technique is the treatment of
      choice.

PMID- 14689071
TI  - [Epidemiology of tuberculosis in Germany].

PMID- 14689072
TI  - [Pathomorphogenesis of tubercular histologic changes: mechanisms of granuloma
      formation, maintenance and necrosis].
AB  - The histopathological hallmark of infections with Mycobacterium tuberculosis is
      the development of centrally necrotizing granulomatous lesions. Granulomas are
      focal accumulations of mononuclear cells in various states of differentiation, in
      which the local activation of mycobacteria-infected macrophages by specific T
      cells takes place. On the one hand, this assures efficient containment of
      mycobacterial growth and demarcation of the infectious focus. On the other hand
      this is associated with the displacement of and irreversible damage to
      functionally vital organ tissue (predominantly in the lungs). New insights,
      emerging from animal models of infection, into the dynamic mechanisms regulating
      the induction, maintenance and caseation of tuberculous granulomas explain why
      highly effective anti-inflammatory therapies, e. g. administration of anti-TNF
      monoclonal antibodies, may result in reactivation of tuberculosis.

PMID- 14689073
TI  - [Immunology of tuberculosis: impact on the development of novel vaccines].
AB  - Tuberculosis is an ancient health problem that is still not under control
      worldwide. High infection rates with the etiologic pathogen, Mycobacterium
      tuberculosis, persisting within the host organism and waiting for the opportunity
      to disseminate when the immune system is suppressed, and the long and cost
      intensive chemotherapeutic treatment urgently require the development of a novel
      vaccine. This article reviews the immune response to M. tuberculosis infection
      resulting in new strategies for the improvement of the available vaccine
      Mycobacterium bovis BCG or for the development of alternative vaccines. A new
      vaccine should elicit a better immune response than the natural infection and
      reliably protect from TB disease, regardless if given prior or post infection
      with M. tuberculosis.

PMID- 14689074
TI  - [Genetics of susceptibility and resistance to tuberculosis].
AB  - As shown in twin studies, the inherited predisposition plays an important role in
      tuberculosis. Genetic influences may be specified in two ways. First, variants of
      genes whose products are involved in apparently disease-relevant pathways may be
      tested in population-based studies. Applying this approach, associations with
      pulmonary tuberculosis have been reported for variants of the genes encoding
      mannose-binding protein, the vitamin-D receptor, natural-resistance associated
      macrophage protein 1, interferon-gamma, of HLA alleles and of the interleukin-1
      gene cluster. Second, genetic influences can be identified by genome-wide studies
      of members of affected families. Thus, linkage has been found between pulmonary
      tuberculosis and as yet undefined genetic variants on chromosome 15q and the X
      chromosome. Further genomic regions of interest have been identified in mouse
      models.

PMID- 14689075
TI  - [Tuberculosis-current therapeutic principles].
AB  - Chemotherapy for tuberculosis is indicated in case of disease as well as in
      latent tuberculosis infection. Standard medication for drug-susceptible
      tuberculosis consists of isoniazid and rifampicin for six months with additional
      pyrazinamide and ethambutol for the first two months. Prolonged treatment is
      necessary in cases of cavernous pulmonary tuberculosis with lack of negative
      cultures by two months of therapy, in tuberculosis of the central nervous system
      and in some cases of superficial lymph node disease. Especially in multiple-drug
      resistant tuberculosis prolonged treatment with three or more drugs, that have
      been proven to be effective by susceptability testing, is mandatory. Attention
      must be payed to reliable delivery of chemotherapy as well as to side effects of
      antituberculosis medications. The classical treatment for latent tuberculosis
      infection is isoniazid. Multidrug short-course therapy, which has been shown to
      be equally effective, enhances patients' compliance, but toxicity is increased.

PMID- 14689076
TI  - [Surgical therapy of pulmonary tuberculosis].
AB  - In individual cases of tuberculosis surgical therapy is part of an
      interdisciplinary therapeutic concept. Identifying the optimal point of time for
      surgery has a strong impact on the further course of the healing process and thus
      on the prognosis. Indications for surgical therapy are: 1. multi-drug-resistant
      pulmonary tuberculosis (MDR-TB), 2. late-onset complications (apergilloma,
      tuberculosis of the tracheobronchial tree or of mediastinal or hilar lymph
      nodes), 3. tuberculosis of the pleura. In MDR-TB an individual concept for
      therapy based on all chemotherapeutic options as well as thorough planning of the
      surgical procedure must be provided. Resections in tuberculotic late-onset
      complications should be performed in patients with persisting cavernous pulmonary
      tuberculosis as well as in patients with post tuberculosis complex; main goal is
      the prevention of tuberculotic relapse. Surgical strategies for tuberculosis of
      the pleura include the debridement of the pleural cavity in video assisted
      surgical technique, decortication, partial thoracoplasty with musculoplasty or
      chest fenestration.

PMID- 14689077
TI  - [44-year-old female patient with cutaneous rash, sore throat, fever and
      arthritis].
AB  - We report on a 44 year old woman with fever, cutaneous rash, severe sore throat,
      arthritis, leukocytosis, splenomegaly and liver dysfunction. After exclusion of
      an infectious or malignant disease, adult onset Still's disease was diagnosed
      according to the Yamaguchi criteria. Reduction of the initial treatment with
      corticosteroids after 4 month caused a relapse of disease. Thus methotrexate
      treatment was started, which resulted in improvement of symptoms and inflammatory
      activity.

PMID- 14689078
TI  - [Acrocyanosis: crucial symptom in a case of chronic diarrhea and weight loss].
AB  - The patient reported here was admitted because of severe dehydration caused by
      watery diarrhea. As underlying disease we found bacterial overgrowth of the small
      bowel due to myopathic dysmotility of the small bowel as a manifestation of CREST
      syndrome. An important clue to the diagnosis was the result of a ward round: the
      patient showed Raynaud's phenomenon when exposed to the cold at an open window
      airing the room. A leading tool for diagnosis and therapy proved to be small
      bowel manometry which is further discussed in this case report.

PMID- 14689079
TI  - [Drug interactions. Mechanisms and clinical relevance].
AB  - During the last few years 3 important drugs (terfenadine, mibefradil, cisapride)
      had to been withdrawn from the market because of serious drug-drug interactions.
      Polypragmacy, not only in advanced age, is often applied. Consequently the
      possibility of pharmacokinetic and/or pharmacodynamic drug interactions has
      always to be taken into account which can cause adverse effects, therapeutic
      failures, hospital admissions and extra costs. Clinically relevant interactions
      can be observed especially on the level of drug metabolism and transport. Both
      pharmacokinetic processes can be induced or inhibited by numerous agents. Taking
      proton pump inhibitors as an example it could be shown that the various compounds
      can differ in their interaction potential.

PMID- 14689080
TI  - [Pravastatin for older patients with risk of vascular disease. The PROSPER
      Study].

PMID- 14689081
TI  - [Internet presence of internist clinics in Germany. Results of a country-wide
      survey of 400 listed clinics].

PMID- 14689083
TI  - [Thyrotoxic crisis].
AB  - Besides the typical and in this case severe signs of hyperthyroidism the
      thyrotoxic crisis is characterized by additional signs and symptoms such as
      fever, cardiac involvement (tachycardia, arrhythmia, heart failure) and central
      nervous impairment eventually leading to coma. Additional diseases and
      comorbidities impair the diagnostic process and may mask the symptoms of
      thyrotoxicosis. If undiagnosed, this situation harbors a mortality of
      approximately 90%. The precise knowledge of typical (and atypical) symptoms is
      mandatory in order to rapidly recognize this situation and to initiate
      pharmacological treatment and/or surgery. An experienced endocrinologist should
      always be involved in this decision process.

PMID- 14689084
TI  - [Hypercalcemic crisis].
AB  - Severe hypercalcemia is a life-threatening medical emergency. It is most commonly
      caused by malignant tumors, but can also be caused by primary hyperparathyroidism
      or less often by a dysregulated production of active vitamin D in granulomatous
      disorders. Symptoms include nausea, vomiting, renal insufficiency, severe
      dehydration, lethargy, confusion, and even coma. Severity of symptoms, calcium
      concentrations, and the overall status of the patient are important
      considerations in selecting appropriate therapy. Hydration to correct volume
      depletion is the cornerstone of acute therapy. Loop diuretics may be added to
      saline hydration after extracellular fluid volume has been replenished to enhance
      urinary calcium excretion and mitigate fluid overload from rehydration.
      Calcitonin and intravenous infusion of bisphosphonates reduce serum calcium
      levels by interfering with calcium release from the skeleton. Dialysis with a low
      or zero calcium dialysate is reserved for patients who are refractory to these
      measures. Corticosteroids are effective with hypercalcemia due to increased
      vitamin D levels and in multiple myeloma.

PMID- 14689085
TI  - [Tetany].
AB  - The hallmark of acute hypocalcemia (ionized calcium <0.75 mmol/l) is tetany,
      which is characterized by neuromuscular irritability. The symptoms may be mild
      with circumoral numbness, paresthesias of hands and feet, and muscular cramps or
      severe with laryngospasm, focal or generalized tonic muscle cramps, or seizures.
      Myocardial dysfunction and prolongation of QT interval also may occur. Most
      often, acute hypocalcemia occurs after thyroid or parathyroid surgery. Rarer
      cases are intravascular binding of ionized calcium by phosphate, citrate, or
      drugs such as foscarnet or bisphosphonates. The most appropriate treatment is
      intravenous calcium, in the form of 100-200 mg of elemental calcium. Thereafter,
      the therapy depends on the underlying disease. In most cases vitamin D has to be
      added to calcium substitution. In cases of hypomagnesemia, magnesium and not
      calcium has to be substituted. It has not yet been proven in clinical trials
      whether substitution of magnesium and/or calcium influences the clinical outcome
      in patients with severe sepsis or pancreatitis who show both hypomagnesemia and
      hypocalcemia.

PMID- 14689086
TI  - [Adrenal crisis. Diagnostic and therapeutic management of acute adrenal cortex
      insufficiency].
AB  - Acute adrenal insufficiency is a rare but life-threatening disorder that develops
      as a result of inadequate adrenal steroid production. Early diagnosis is key for
      effective and life-saving treatment of the affected patients. The main clinical
      features are non-specific, thus often leading to misdiagnosis and invasive
      diagnostic work up, in particular in patients with previously unknown disease.
      Adrenal crisis in patients with known chronic adrenal insufficiency is nowadays
      rare, but can only be prevented by structured patient education on stress-related
      glucocorticoid dose adjustment. Outcome of adrenal crisis is crucially determined
      by the physician's clinical competence and immediate initiation of specific
      treatment.

PMID- 14689087
TI  - [Hypophyseal coma].
AB  - Pituitary coma is a rare case of emergency and primarily due to ACTH and TSH
      deficiency. Pituitary coma occurs more often in patients with well-known
      pituitary deficiency than in patients with intrasellar tumor. Clinical
      manifestations are hypotonia, bradycardia, decreased skin and nipple
      pigmentation, muscle weakness, vomitus, nausea, obstipation, hypothermia, and
      hypoventilation. A postpartal agalactia is often the first sign of Sheehan's
      syndrome. Unlike primary adrenal insufficiency (Addison's disease) ACTH
      deficiency does not cause hyperpigmentation, hyperkalemia, or salt loss. The
      suspicion of pituitary coma requires replacement with 100 mg hydrocortisone iv,
      200 mg hydrocortisone iv/24 h, 500 micro g levothyroxine iv and fluid
      substitution. Since thyroxine accelerates the degradation of cortisol and can
      precipitate adrenal crisis in patients with limited pituitary reserve,
      hydrocortisone replacement should always precede levothyroxine therapy. ACTH
      stimulation test, CRH stimulation test and insulin tolerance test (optional)
      should be performed after therapeutic compensation to determine pituitary
      function.

PMID- 14689088
TI  - [Diabetic coma. Management of diabetic ketoacidosis and nonketotic hyperosmolar
      coma].
AB  - This review describes the current guidelines of German diabetes association for
      the management of diabetic coma, both of diabetic ketoacidosis and hyperosmolal
      coma. The outline focuses on emergency treatment and the management on the
      intensive care unit, in particular, volume and insulin therapy, and potassium
      replacement. The delineation of the concept of low insulin therapy is emphasized
      to avoid the incidence of disequilibrium syndrome. Also, the indications for
      bicarbonate therapy in diabetic ketoacidosis are critically discussed, as well as
      phosphate and magnesium replacement. With today's therapeutic possibilities the
      therapeutic goal, i.e. a low mortality, may be achieved, dependent on the
      underlying illness.

PMID- 14689090
TI  - [44-year-old patient with fulminant liver failure].
AB  - The 44-year old female patient was admitted with acute hepatic failure and
      extensive haemolysis under the preliminary diagnosis of Wilson's disease. General
      characteristic criteria of Wilson's disease as Kayser-Fleischer ring, low serum
      copper and low ceruloplasmin levels were not observed. The preliminary diagnosis
      of acute Wilson's disease was established on the basis of the characteristic
      laboratory values with an AP/bilirubin ratio <2, an AST/ALT ratio >4,
      accompanying hemolysis and a highly elevated cupruresis. The definitive diagnosis
      of Wilson's disease was verified after orthotopic liver transplantation by
      quantitative copper evaluation in the explanted liver. The case represents the
      yet oldest patient reported with an acute manifestation of Wilson's disease.

PMID- 14689089
TI  - [Hypoglycemia, classification, therapy and preventable errors].
AB  - Hypoglycemia is a multifactorial problem that is caused by the interaction of
      numerous variables such as a individual pathophysiological response, treatment
      aspects and self control. In particular, the increasing use of intensified
      insulin therapy and thus the goal of normoglycemia has made hypoglycaemia to
      become a major hazard among the acute complications of diabetes mellitus. Early
      diagnosis and treatment is thus mandatory to reduce the increased morbidity and
      mortality of hypoglycaemia. Among the acute therapy of hypoglycaemia treatment
      includes a modification of diabetes therapy, patient education and a special
      training of hypoglycaemia awareness.

PMID- 14689091
TI  - [Syncope in a young man of Turkish origin].
AB  - A young male patient of Turkish origin developed a syncope after the consumption
      of so-called "pontic honey" from the black sea coast. Further symptoms were sinus
      bradycardia, hypotension and gastrointestinal problems. Intoxication caused by
      grayanotoxins was presumed. Complete recovery occurred within a few hours under
      symptomatic therapy. Intoxication due to grayanotoxins from "pontic" honey are
      rare in Western Europe and should be taken into consideration in patients with
      unexplained bradycardia and a travel history to countries of the black sea coast.

PMID- 14689092
TI  - [Hypogonadism in the elderly man. Reliable diagnosis and therapy].
AB  - The definition of late-onset-hypogonadism as a hybrid form of primary and
      secondary hypogonadism corresponds to pathophysiological facts of the age-related
      decline in gonadal as well as hypothalamic-pituitary functions, eventually
      manifesting in clinically relevant hypogonadism. To what extent advancing age
      modulates incidence and nature of hypogonadal symptoms has not been completely
      investigated. The benefits of testosterone substitution therapy in older men
      await demonstration in long-term studies and to date, it should be restricted to
      specialized centers. Currently, serum testosterone levels <12 nmol/l, accompanied
      by symptoms of androgen deficiency, are regarded as an indication for
      substitution, provided a prostate carcinoma has been excluded. While late-onset
      hypogonadism decreases libido, it does not play a direct role in the increasing
      incidence of erectile dysfunction with advancing age; this symptom is rather
      associated with vessel-endothelial impairment and may serve as a sentinel symptom
      for cardiovascular disease. Treatment with phosphodiesterase-5-inhibitors can be
      regarded as standard; in case of concomitant late-onset hypogonadism,
      testosterone will have a positive synergistic effect on erectile function.

PMID- 14689093
TI  - [Acetylsalicylic acid for prevention of colorectal adenomas. The APP Study].

PMID- 14689095
TI  - [Adequate anticoagulation in atrial fibrillation].

PMID- 14689096
TI  - [No increased costs with PET scan].

PMID- 14689097
TI  - [Hypertension--only high blood pressure?].

PMID- 14689098
TI  - Genetics of human hypertension.
AB  - BACKGROUND: Hypertension is a multifactorial disease involving interactions among
      genetic, environmental, demographic, vascular and neuroendocrine factors.
      Essential hypertension is the most frequent diagnosis in this syndrome,
      indicating that a monocausal etiology has not been identified. However, a number
      of risk factors underlying essential hypertension have also been identified
      including age, sex, genetics, demographic factors, and others. Remarkable
      progress in molecular biological research has been achieved in clarifying the
      molecular basis of Mendelian hypertensive disorders. Causative genes and
      chromosomal fragments harboring disease susceptibility genes have been
      identified, e. g., for glucocorticoid-remediable aldosteronism, Liddle's
      syndrome, mineralocorticoid excess. MOLECULAR GENETIC STUDIES: Molecular genetic
      studies have now identified mutations in eight genes that cause Mendelian forms
      of hypertension and nine genes that cause Mendelian forms of hypotension in
      humans. No single genetic variant has emerged from linkage or association
      analyses as consistently related to blood pressure level in every sample and in
      all populations. However, a number of polymorphisms in candidate genes have been
      associated with differences in blood pressure. Most prominent have been the
      polymorphisms in the renin-angiotensin-aldosterone system. CONCLUSION: Essential
      hypertension is likely to be a polygenic disorder that results from the
      inheritance of a number of susceptibility genes and involves multiple
      environmental determinants. These determinants complicate the study of blood
      pressure variations in the general population. The complex nature of the
      hypertension phenotype makes large-scale studies indispensable, when screening of
      familial and genetic factors is intended.

PMID- 14689099
TI  - Kidney and hypertension-causes. Update 2003.
AB  - Renal disease is closely associated with hypertension. On the one hand, kidney
      disease provokes hypertension. On the other hand, hypertension aggravates the
      progression of renal dysfunction. The pathomechanisms through which the kidney
      raises blood pressure have been considerably clarified in recent years. In
      experimental and clinical studies, it could be shown that "hypertension goes with
      the kidney". This suggests that some renal anomalies predispose to hypertension.
      Recently, it could be shown that the kidneys of individuals with so-called
      essential hypertension have less glomeruli than the kidneys of control
      individuals. In renal patients the kidney raises blood pressure through several
      mechanisms. First, the pressure-natriuresis relationship is shifted to the right,
      i. e., sodium excretion requires higher renal perfusion pressures. Second, there
      is inappropriate activation of the renin-angiotensin system. Third, as only
      recently documented in detail, renal injury raises the sympathetic tone, even
      when whole kidney glomerular filtration rate (GFR) is unchanged. This results
      from stimulating afferent signals emanating from the kidney. Fourth, there is
      evidence of impaired endothelial cell dependent vasodilatation even in very early
      stages of renal dysfunction. Fifth, the pulse pressure profile is altered as a
      consequence of premature and accelerated aging causing stiffening of the aorta.
      Knowledge of these pathomechanisms is important for selection of appropriate
      antihypertensive treatment.

PMID- 14689100
TI  - Abdominal fat and sympathetic overactivity. From calorie intake to postmenopausal
      hypertension.
AB  - BACKGROUND: Epidemiologic studies have found an association between overweight
      and increased mortality arising primarily from cardiovascular disorders. A major
      determinant is a chronically raised sympathetic nervous system activity which can
      arise from calorie intake-dependent and -independent mechanisms. Calorie
      dependent parameters reflecting sympathetic overactivity are an increased body
      fat mass and body mass index. VISCERAL FAT: Although influenced by calorie intake
      to a certain extent, visceral fat accumulation is a mechanism which is determined
      also by estrogen deficiency (postmenopausal hypertension) or enhanced corticoid
      influences. It is hypothesized that excess catecholamines trigger various adverse
      processes which, if they persist, can lead or aggravate hypertension and insulin
      resistance. Visceral but not peripheral fat mass was correlated with atherogenic
      metabolites. EXCESS CATECHOLAMINE SYNDROME: The present focus on visceral fat
      accumulation strengthens the concept of an "excess catecholamine syndrome" of
      which the "metabolic syndrome" appears as one consequence. It is proposed to
      further assess the potential of transthoracic echocardiography as routine imaging
      method for the prediction of visceral fat accumulation and its adverse health
      consequences.

PMID- 14689101
TI  - [Arterial hypertension and metabolic syndrome].
AB  - BACKGROUND AND THERAPY: The metabolic syndrome comprises a virulent and lethal
      group of atherosclerotic risk factors, including dyslipidemia, obesity, systemic
      hypertension and insulin resistance. The prevalence of the metabolic syndrome has
      continuously grown in industrialized and developing countries during the last
      decades, and affects tens of millions of people in Germany and Europe.
      Particularly prominent as a risk factor for the development of insulin resistance
      is central obesity, which is causally involved in the pathogenesis of insulin
      resistance in addition to genetic predisposition. The metabolic syndrome can
      easily be diagnosed in clinical practice (guidelines of the WHO and ATP III
      panel), and immediate treatment of the metabolic syndrome is mandatory because
      those patients are at increased risk to develop overt diabetes mellitus, coronary
      artery disease and stroke. The high risk for cardiovascular diseases is supported
      by findings that the risk for myocardial infarction in patients with insulin
      resistance is as high as the risk of patients after their first myocardial
      infarction. Intentional weight reduction reduces abdominal obesity and
      beneficially modulates all features of the metabolic syndrome, while the benefits
      of aerobic exercise training are discussed controversially. Thus, weight
      reduction causally undoes essential features of the metabolic syndrome, but
      effects are often not enduring. Therefore, the treatment of cardiovascular risk
      factors such as hypertension and dislipidemia is essential. Of note,
      antihypertensive treatment is more effective than tight glucose control to reduce
      cardiovascular events. Diuretics, ACE-inhibitors and angiotensin II type 1
      receptor antagonists are suggested as first line therapeutics. However, at least
      two antihypertensives are usually necessary to achieve the suggested goals of
      blood pressure reduction. In conclusion, the prevalence of the metabolic syndrome
      is continuously growing. Due to its adverse impact on cardiovascular disease,
      early detection and aggressive treatment is mandatory to ensure longlasting
      benefits for affected patients.

PMID- 14689102
TI  - [The aldosterone to Renin ratio in secondary hypertension].
AB  - CLASSICAL FEATURES AND SCREENING: The classical features of primary aldosteronism
      hypertension, hypokalemia and metabolic alkalosis-were first described by J. Conn
      in the midfifties of the last century. The classical form of primary
      aldosteronism is a rare disease with prevalence rates of 0.1-0.5% within the
      hypertensive population. The normokalemic variant of primary aldosteronism seems
      to be much more frequent (5-13%). Although a validated and standardized
      diagnostic protocol for this entity is still missing recent studies established
      the aldosterone to renin ratio as a useful screening test. To increase diagnostic
      sensitivity and specificity of the ratio aldosterone should be added as second
      screening criterion (sensitivity and specificity about 90%). Dynamic confirmatory
      testing proving autonomous aldosterone secretion is required to verify the
      diagnosis in case of a positive screening test. A simple confirmatory test is the
      salt loading test. Alternatively, the fludrocortisone-suppression-test, the
      Captopril-challenge- test or the daily exretion rate of aldosterone-18
      glucuronide and tetrahydroaldosterone in urine can be used. In case of proven
      primary aldosteronism further diagnostic evaluation (e. g. CT scanning, postural
      test and in case of discrepancy adrenal vein catheterization) is mandatory to
      differentiate the most common forms of primary aldosteronism, aldosterone
      producing adenoma and idiopathic hyperaldosteronism. Since many patients with
      primary aldosteronism can be cured by surgery and missing the diagnosis often
      leads to significant end-organ damage it is important to evaluate hypertensive
      patients with therapy-resistant hypertension for primary aldosteronism.

PMID- 14689103
TI  - A neuroendocrine-immune interface. The immunostimulatory state of aldosteronism.
AB  - Hypertension is an important determinant of heart failure. Ventricular systolic
      and/or diastolic dysfunction can eventuate in an activation of the renin
      angiotensin-aldosterone system (RAAS). Circulating RAAS effector hormones lead
      to: the appearance of the congestive heart failure syndrome; and a systemic
      illness that features oxi/nitrosative stress in various tissues, including blood,
      together with circulating pro-inflammatory cytokines, anorexia and, ultimately,
      cachexia. In addition to its well-known endocrine properties, expressed in
      epithelial cells of classic target tissues, aldosterone (ALDO) has an emerging
      portfolio of actions in nonclassic target tissues, such as circulating
      lymphocytes and monocytes (or peripheral blood mononuclear cells [PBMC]). This
      neuroendocrine-immune interface is based on Na(+)-dependent, ALDO-induced
      iterations in PBMC cytosolic free [Mg(2+)](i) and [Ca(2+)](i). Ca(2+) loading
      contributes to an induction of oxi/nitrosative stress and activation of PBMC
      transcriptome. This immunostimulatory state begets a pro-inflammatory/fibrogenic
      vascular phenotype involving the heart and systemic organs and can be prevented
      by either ALDO receptor antagonism or antioxidant. The established efficacy of
      ALDO receptor antagonism as an integral component of the overall management of
      symptomatic heart failure may include its immunomodulatory properties. This brief
      review traces studies that led to and then identified the neuroendocrine-immune
      interface that accompanies aldosteronism.

PMID- 14689104
TI  - [Systolic hypertension-treat or not to treat?].
AB  - HEMODYNAMICS: Elevated diastolic as well as elevated systolic blood pressure
      substantially contribute to the increase of cardiovascular risk. Conclusive
      results have proven that lowering diastolic and/or systolic blood pressure can
      reduce cardiovascular risk. There is evidence that not only the absolute values
      for diastolic and systolic blood pressure alone but also the pulse pressure as an
      additional indicator of cardiovascular risk have to be considered. The prevalence
      of isolated systolic hypertension increases with age. Remodeling of the arterial
      wall with increase of collagen and decrease of elastic fibers are leading to an
      impaired arterial compliance. Decreased compliance and acceleration of the pulse
      wave velocity can elevate systolic and lower diastolic blood pressure. In
      consequence cardiac stress and pulse pressure will rise. CONCLUSION: There is a
      strong correlation in elderly patients between cardiovascular mortality and
      morbidity and systolic blood pressure. Antihypertensive therapy is able to lower
      cardiovascular event rate in elderly patients with isolated systolic hypertension
      with a predominant risk reduction for stroke.

PMID- 14689105
TI  - [Cerebrovascular sequelae of hypertension].
AB  - Hypertension is the most important risk factor for stroke and vascular dementia.
      Antihypertensive treatment reduces stroke risk by 40%. Most probably, all
      antihypertensive drugs are equally effective with the exception of alpha
      blockers. One study showed superiority of an angiotensin (AT) II antagonist
      versus beta blocker in patients with hypertension and left ventricular
      hypertrophy. Blood pressure is increased in many patients with acute stroke. In
      this phase, sudden drops in blood pressure should be avoided. All guidelines
      concerning antihypertensive treatment in acute stroke are not based on evidence.
      For secondary prevention, the combination of an angiotensin- converting enzyme
      (ACE) inhibitor and diuretic reduced strokes by 28% after transient ischemic
      attack (TIA) or a first stroke. Whether this is a drug-specific effect or due to
      lowering blood pressure per se is investigated at the moment. Antihypertensive
      treatment can reduce the incidence of vascular dementia and cognitive impairment.

PMID- 14689106
TI  - [Hypertensive emergency and urgence].
AB  - DEFINITION, PATHOPHYSIOLOGY, THERAPY: The hypertensive crisis is characterized by
      a massive, acute rise in blood pressure. Patients with underlying hypertensive
      disease usually have an increase in systolic blood pressure values > 220 mmHg and
      diastolic values > 120 mmHg. The severity of the condition, however, is not
      determined by the absolute blood pressure level but by the magnitude of the acute
      increase in blood pressure. Thus, in the presence of primarily normotensive
      baseline values (such as those in eclampsia), even a systolic blood pressure >
      170 mmHg may lead to a life-threatening condition. The most important causes are
      non-compliance (reduction or interruption of therapy), inadequate therapy,
      endocrine disease, renal (vessel) disease, pregnancy and intoxication (drugs).
      The management of this condition greatly depends on whether the patient has a
      hypertensive crisis with organ manifestation (hypertensive emergency) or a crisis
      without organ manifestation (hypertensive urgency). By documenting the medical
      history, the medical status and by simple diagnostic procedures, the differential
      diagnosis can be established at the emergency site within a very short period of
      time. In the absence of organ manifestations (hypertensive urgency) the patient
      may have non-specific symptoms such as palpitations, headache, malaise and a
      general feeling of illness in addition to the increase in blood pressure. In a
      hypertensive urgency the patient's blood pressure should not be reduced within a
      few minutes but within a period of 24 to 48 hours. Such adjustment can be
      achieved on an out-patient basis, however, only if the patient can be followed up
      adequately for early detection of a renewed attack. In the absence of follow-up
      facilities, the patient's blood pressure should be reduced over a period of 4 to
      6 hours, if necessary in an out-patient emergency service. While intravenous
      medication is given preference when a rapid effect is desired, oral medication
      may be used for gradual reduction on an out-patient basis, depending on the
      patient's medical history and on any underlying chronic disease. Organ
      manifestations in the course of a hypertensive emergency concern the
      cardiovascular system and are associated with the symptoms of acute left
      ventricular heart failure, the acute coronary syndrome or acute aortic
      dissection. In the brain the patient may have symptoms of hypertensive
      encephalopathy, hemorrhage, ischemia; in the kidney he/she may develop acute
      failure. The patient's blood pressure should be reduced rapidly during the
      treatment. It should not be reduced to the normal value, but by approximately 20
      30% of the baseline value. The reason for a stepwise reduction in blood pressure
      is the fact that patients with chronic hypertension have an altered
      autoregulation curve. Acute normotension would lead to hypoperfusion in these
      patients. Those with aortic dissection or pulmonary edema are excepted from the
      rule of gradual blood pressure reduction. In the presence of these diseases,
      blood pressure must be reduced rapidly to normal values. Patients with a
      hypertensive emergency should always be admitted to the hospital. Parenteral
      treatment is given preference, since the effect of the treatment is rapid and
      occurs within a calculable period of time. Thus, parenteral treatment can also be
      better regulated than medication administered orally or by the sublingual route.
      Several antihypertensives are available for this purpose. The selection of the
      substance greatly depends on the existing organ failure as well as the reliable
      effectiveness and the regulability of the applied antihypertensive.

PMID- 14689107
TI  - Combination versus Monotherapy as Initial Treatment in Hypertension.
AB  - Monotherapy is able to normalize blood pressure in less than a quarter of
      patients with hypertension. However, for a disease of multifactorial pathogenesis
      like essential hypertension, a therapeutic strategy employing different
      principles of actions is most suitable. In addition, combination therapy has many
      advantages. Blood pressure reduction is improved by an additive effect and
      through neutralization of compensatory counter-regulatory reactions. The number
      and severity of adverse effects are reduced by lower dose requirements. Some
      clinical trials have documented blood pressure-independent, i. e., true
      synergistic, organ-protective effects. Furthermore, combination therapy is
      expected to reduce costs and to improve therapeutic compliance. In a clinical
      trial, initial low-dose combination therapy has been shown to be superior as
      compared to treatment by the stepped-care and the sequential monotherapy
      approach. Recently, therefore, low-dose combination therapy has been recommended
      for initial antihypertensive therapy instead of the stepped-care approach or of
      sequential monotherapy.

PMID- 14689108
TI  - Angiotensin II antagonists in the treatment of hypertension-effective and
      efficient?
AB  - AIM: Aspects of care such as efficacy, effectiveness and efficiency have to be
      taken into account prior to the implementation of any new antihypertensive
      medication into routine medical care. METHODS AND RESULTS: The efficacy of
      angiotensin (AT) II antagonists in lowering blood pressure was summarized in a
      meta-analysis including 43 trials and a total of 11,281 patients. The four AT II
      antagonist classes losartan, valsartan, irbesartan, and candesartan were studied
      and achieved a mean reduction in systolic blood pressure between 10.4 und 11.8
      mmHg and in diastolic blood pressure between 8.2 und 8.9 mmHg. The effectiveness
      of AT II antagonist therapy in reducing clinical events such as stroke or end
      stage renal disease in hypertension and associated conditions was shown in a
      number of large trials. Also, less adverse events were reported for AT II
      antagonist therapy compared to other antihypertensive medication such as beta
      blockers and angiotensin-converting enzyme (ACE) inhibitors. However, the number
      of trials is still comparatively small. Several ongoing trials will provide
      further insight into the effectiveness of AT II antagonist therapy. CONCLUSION:
      The efficiency of AT II antagonist therapy in being a cost-effective alternative
      for reducing clinical events in patients with hypertension requires further
      research. The combination of data from clinical trials with epidemiologic data
      about the natural history of the disease and factors such as patient compliance,
      side effects, acquisition costs or medication switch is needed to reflect costs
      in the "real-world" situation.

PMID- 14689109
TI  - [Diuretics-first line treatment for hypertension?].
AB  - STUDY RESULTS: The role of diuretics in the treatment of arterial hypertension
      remains a matter of controversy. On the basis of the results of recent studies
      and economic considerations a broader use of diuretics in the initial
      antihypertensive therapy has been proposed. The present review analyses two
      aspects of diuretics which are of interest in this debate. Thus, several studies
      demonstrate that diuretic therapy is associated with a greater incidence of new
      onset diabetes as compared to calcium channel blockers, ACE-inhibitors and AT(1)
      antagonists. The clinical relevance of this effect becomes clear when calculating
      the "numbers needed to treat" (NNT) on the basis of a long-term therapy over
      several decades. Based on the assumption of linear increases in the incidence of
      diabetes over time NNT then become remarkably small and in some studies number <
      10. Another problem associated with diuretics is the low compliance and
      persistence with this type of drugs established in "real life" studies in which
      patients were not disciplined by the study design. These characteristics of
      diuretic therapy of hypertensive patients challenge the proposed medical and also
      economic benefit of diuretics as compared to more "modern" antihypertensive
      agents.

PMID- 14689110
TI  - Effects of ACE inhibition versus non-ACE inhibitor antihypertensive treatment on
      myocardial fibrosis in patients with arterial hypertension. Retrospective
      analysis of 120 patients with left ventricular endomyocardial biopsies.
AB  - BACKGROUND AND PURPOSE: In experimental arterial hypertension, left ventricular
      hypertrophy (LVH) becomes pathologic with impaired myocardial function if
      myocardial fibrosis occurs. Myocardial fibrosis is associated with activated
      circulating or local renin-angiotensin-aldosterone systems. The primary objective
      of this retrospective study was to determine whether patients with arterial
      hypertension treated with angiotensin-converting enzyme inhibitors (ACEI) have
      less myocardial fibrosis than patients on non-ACEI treatment. MATERIAL AND
      METHODS: We examined left ventricular (LV) endomyocardial biopsies of 97
      consecutive patients with hypertensive heart disease due to primary hypertension
      treated with either any ACEI for at least 6 months (n = 34; HTN + ACEI) or non
      ACEI antihypertensive drugs (n = 63; HTN). Normal hearts designated for heart
      transplantation served as controls (n = 23; CTR). Myocyte diameter (MyoD) and
      collagen volume fraction (CVF) were measured by morphometry, and pro-matrix
      metalloproteinases (proMMPs) 2 and 9 by zymography. In a subset of 35 patients,
      LV myocardial stiffness was determined by left heart catheterization with
      calculation of stiffness constant k. RESULTS: In HTN + ACEI or HTN, MyoD (21.8 +/
      0.3 micro m and 22.4 +/- 0.3 micro m, respectively) and CVF (5.3 +/- 0.6% and
      7.6 +/- 0.7%, respectively) were increased (p < 0.01) compared with CTR (16.0 +/-
      0.4 micro m and 0.5 +/- 0.2%, respectively). In HTN + ACEI, CVF was significantly
      lower (p < 0.02) and proMMP 2 was higher (0.063 +/- 0.013 OD/mg) compared with
      HTN (0.037 +/- 0.006 OD/mg; p < 0.05) while no significant difference of MyoD was
      evident. We found no correlation between CVF and MyoD (r = 0.13; p = 0.47), a
      positive correlation between k and CVF (r = 0.71; p < 0.00001), and no
      correlation between k and MyoD (r = 0.22; p = 0.24). CONCLUSION: In patients with
      hypertensive heart disease, myocyte hypertrophy and myocardial fibrosis are
      present. Myocardial fibrosis and not myocyte hypertrophy determines myocardial
      stiffness. ACEI appear to diminish myocardial fibrosis associated with enhanced
      collagen degradation irrespective of LVH regression.

PMID- 14689111
TI  - [Differential therapy with calcium antagonists].
AB  - EFFICACY OF CALCIUM ANTAGONISTS: Calcium-channel blockers (CCBs) have long been
      recognized as potent agents for hypertensive therapy, with substantial blood
      pressure reduction in all age groups and races. CCBs improve endothelial
      function, may positively influence atherosclerosis in carotid arteries, reduce
      left ventricular hypertrophy, and hypertrophy of the resistance vessels, and
      improve arterial compliance. They do not adversely affect lipids and serum
      glucose. USE IN PRACTICE: CCBs are also a heterogenous class of drugs composed of
      the phenylalkylamine verapamil, the benzothiazepine diltiazem, and the large
      group of dihydropyridines (DHPs) with the prototype nifedipine, and an increasing
      number of newer agents (e. g. nitrendipine, nisoldipine, amlodipine, felodipine,
      lacidipine and lercanidipine). DHPs are primarily vasodilators, lowering blood
      pressure by decreasing peripheral vascular resistance at the level of the small
      arterioles which can be followed by an autonomic counterregulation especially in
      drugs with a rapid onset of action. This is markedly reduced or abolished in the
      treatment with the modern long acting DHPs and is also not the case in the
      treatment with non-DHPs. Prospective randomized controlled outcome studies
      demonstrated a significant reduction in stroke in elderly patients with isolated
      systolic hypertension compared with placebo (Syst-Eur [Syst-China]), and no
      significant differences in cardiovascular mortality and combined morbidity
      compared with diuretics, beta blockers or ACE-Inhibitors (STOP-2, INSIGHT,
      NORDIL, ALLHAT, INVEST). To normalize the blood pressure it is mostly necessary
      to combine antihypertensive drugs. Here are CCBs ideal partners for a therapy
      with ACE-inhibitors, AT1 antagonists or beta blockers (DHP) and diuretics
      (verapamil). With respect to the antihypertensive differential therapy the author
      recommends CCBs based on studies with the evidence grade 1-3; especially for
      elderly hypertensives (with isolated systolic neuhypertension and a high risk of
      stroke), for patients with COPD and asthma bronchiale, Raynaud's syndrome or
      Prinzmetal-angina, patients with diastolic function disturbances including
      diastolic heart failure or hypertensives with massive left ventricular
      hypertrophy (in combination with ACE or AT1 inhibitors).

PMID- 14689112
TI  - [Regression of left ventricular hypertrophy in hypertensive heart disease].
AB  - PATHOPHYSIOLOGY AND THERAPY: Left ventricular hypertrophy represents an important
      factor determining the prognosis of hypertensive patients. Hypertrophy as
      identified by electrocardiography (Table 1) or echocardiography (Table 2)
      characterizes patients with a significantly increased risk of mortality and
      arrhythmia. From the pathophysiological point of view this is based on
      hypertrophy of the media in resistance vessels, on interstitial fibrosis, on a
      reduced coronary flow reserve and on the occurrence of ischemia (Figure 1). The
      diastolic and (later) systolic function of the heart are disturbed (Figures 2 to
      4). Antihypertensive therapy with beta blockers and diuretics leads to a
      reduction of left ventricular mass by 5-8%, with ACE-inhibitors and AT-blockers
      by 13% (Figure 5). Particularly ACE-inhibitors can effectively reverse of the
      above mentioned pathological processes. Regression of hypertrophy goes along with
      an improved prognosis and a reduction of atrial and ventricular arrhythmias
      (Figure 6). A symptomatic treatment of arrhythmias should always be accompanied
      by medical therapy aimed at regression of hypertrophy. Optimal therapy results in
      normalizes of blood pressure, leads to a regression of hypertrophy and induces
      cardiac reparation, which in turn improve left ventricular function, reduces
      microvascular ischemia stress and arrhythmias. These therapeutic desiderates are
      also pertinent for hypertensive heart disease in the prehypertrophic state, as in
      juvenile hypertension.

PMID- 14689113
TI  - Alpha 1-antitrypsin deficiency associated iatrogenic coronary artery dissection
      during intracoronary ultrasound examination.

PMID- 14689115
TI  - [Three-dimensional reconstruction of pulmonary veins and left atrium.
      Implications for catheter ablation of atrial fibrillation].
AB  - BACKGROUND: Selective pulmonary vein (PV) isolation to eliminate triggers is
      commonly used for curative catheter ablation of atrial fibrillation guided by two
      dimensional (2-D) PV angiography, which is somewhat limited to depict the complex
      morphology of the PVs. 3-D mapping systems are limited to reconstruct the
      complete "true" anatomy by the reach of the mapping electrode related to catheter
      properties (maximum deflection and curve). New 3-D imaging systems (spiral
      computed tomography [CT] or magnetic resonance imaging [MRI]) provide detailed
      knowledge of the individual left atrial and PV morphology. Especially with the
      tampering, funnel-shaped PV ostia, identification of the PV ostium in selective
      PV isolation procedures aiming at the interruption of myocardial fibers is rather
      challenging using the 2-D imaging technique of contrast angiography. PATIENTS AND
      METHODS: In a total of 16 patients (13 male, three female, mean age 57 +/- 8
      years), cardiac 3-D magnetic resonance angiography (MRA; 1.5 T, ACS Intera
      Philips, Germany) using an ECG-gated technique (1.3-1.7 mm slices) was performed.
      Using the postprocessing software Leonardo (Siemens, Germany), all adjacent
      anatomic structures such as the pulmonary artery were cut off to focus on the
      left atrium (LA) and PV anatomy. RESULTS: Left-sided PVs always entered in close
      proximity into the LA (common ostium in two patients). The right PVs entered more
      separately into the LA with a predominance of oval shapes. CONCLUSION: MRA is a
      noninvasive tool providing knowledge of the individual 3-D anatomy in a
      photorealistic fashion. Ultimately, image fusion with 3-D mappings systems would
      allow for true 3-D electrophysiologic mapping and could facilitate further
      understanding of the underlying substrate of so far "unsolved" complex
      arrhythmias such as atrial fibrillation in the future.

PMID- 14689116
TI  - [3-d mapping of pulmonary veins using a multipolar basket catheter. Implications
      for catheter ablation of atrial fibrillation].
AB  - BACKGROUND: Focal discharges from pulmonary veins are the major sources of
      paroxysmal atrial fibrillation. The aim of this study was to analyze the
      activation pattern of pulmonary veins during sinus rhythm and ectopy with the
      help of a multipolar basket catheter and to disconnect them from the left atrium
      by localized radiofrequency catheter ablation. PATIENTS AND METHODS: We studied
      65 patients (43 male, 22 female, mean age 54 +/- 12 years) with drug-refractory
      atrial fibrillation (paroxysmal n = 42, persistent n = 23). A 64-pole basket
      catheter (Figure 1) with a diameter of 31 or 38 mm (Constellation, Boston
      Scientific) was placed transseptally into the pulmonary veins to record its
      activation during ectopic beats and during sinus rhythm or coronary sinus pacing
      (Figure 2). The ablation catheter was placed as ostial as possible next to the
      electrodes showing the earliest pulmonary vein activation during sinus rhythm or
      coronary sinus pacing (Figures 3 and 4a). The radiofrequency energy was delivered
      with a maximum temperature of 50 degrees C and a maximum power of 30 W. In 32
      patients, an irrigated-tip catheter (Thermocool, Biosense-Webster) was used.
      Endpoint of the procedure was the complete elimination of all distal pulmonary
      vein potentials during sinus rhythm (Figure 4b). RESULTS: The mean number of
      procedures per patients was 1.25, mean procedure time 236 +/- 79 min, and mean
      fluoroscopy time 40 +/- 17 min, respectively. In 16 veins, repetitive discharges
      (more than three) could be recorded under stable conditions (Figures 2 and 5). In
      twelve of these 16 pulmonary veins (75%), the activation pattern during ectopic
      beats was identical in the same vein, but different from one vein to another
      (Figure 2). In four veins, changing activation patterns were observed in the same
      vein. Focal atrial fibrillation was recorded in four pulmonary veins (Figures 6
      and 7). A total of 187 out of 190 mapped veins were successfully isolated at the
      ostium by ablating 2.3 +/- 1.1 separated conduction pathways. In 16 patients, a
      second EP study was performed for recurrence of atrial fibrillation. Recovery of
      conduction of a previously isolated pulmonary vein was identified as the primary
      reason for recurrence of atrial fibrillation. The second reason were ostial foci,
      localized proximal to the ablation line (Figure 8). COMPLICATIONS AND FOLLOW-UP:
      One pericardial tamponade occurred. Carbonization on the splines of the basket
      catheter-observed in twelve cases with use of a nonirrigated-tip catheter-was
      prevented by use of irrigated-tip catheters. At 12 months, 36 out of 65 patients
      (55%) are in sinus rhythm without antiarrhythmic drug use, 28 of 42 patients
      (67%) with paroxysmal atrial fibrillation. Only one pulmonary vein stenosis > 50%
      was detected by angiomagnetic resonance imaging 1 year after the procedure.
      CONCLUSION: 75% of the arrhythmogenic pulmonary veins showed a stable and
      specific pattern during repetitive ectopic activity. Ostial ablation of 2.3 +/-
      1.1 separated conduction pathways from the left atrium into the pulmonary veins
      resulted in complete conduction block in 187 of 190 veins.

PMID- 14689117
TI  - [Non-contact mapping of the left atrium using a multi electrode mapping array].
AB  - In contrast to the sequential mapping systems such as the conventional and the
      electroanatomic mapping, the non-contact mapping provides simultaneous mapping.
      The non-contact-mapping system detects far-field endocardial potentials from a
      multielectrode-array catheter and reconstructs over 3,000 unipolar virtual
      electrograms. Based on the virtual electrograms, the system produces an
      instantaneous three-dimensional (3-D) isopotential map. High-density mapping of
      the endocardial activation sequence allows immediate and simultaneous
      identification of a propagation vector along the line and the identification of
      an arrhythmogenic focus on a single beat. The methods and results of different
      ablation strategies for atrial fibrillation using the non-contact-mapping system
      are reported.

PMID- 14689118
TI  - Electroanatomic mapping of the endocardium. Implication for catheter ablation of
      ventricular tachycardia.
AB  - The electroanatomic mapping system Carto((R)) with its combination of anatomic
      and electrophysiologic information has substantially improved our understanding
      of arrhythmia mechanisms and substrates in patients with ventricular tachycardia
      (VT) and structural heart disease. Identification of the individual
      arrhythmogenic substrate and successful ablation guided by the combination of
      sinus rhythm voltage mapping and conventional electrophysiologic techniques like
      pace and activation/entrainment mapping are best described for patients with
      recurrent VT in remote myocardial infarction. In about 75-90% of the patients,
      the target VT can be ablated with acute success and the patients remain free of
      any VT recurrence in up to 75%. First results of electroanatomically guided
      ablation in patients with arrhythmogenic right ventricular dysplasia are
      promising. Data on ablation of VT in other structural heart diseases are very
      limited, since the arrhythmogenic substrate is very diffuse, e. g., in dilated
      cardiomyopathy, or there are only small patient numbers, e. g., for cardiac
      sarcoidosis or monomorphic VT after repair of congenital heart disease. In this
      article, the current status of electroanatomically guided endocardial mapping and
      ablation of VT in patients with structural heart disease is described.

PMID- 14689119
TI  - Catheter ablation of subepicardial ventricular tachycardia using electroanatomic
      mapping.
AB  - BACKGROUND: In patients with left ventricular tachycardia (VT) and failed
      endocardial ablation, a subepicardial substrate may be considered. PATIENTS AND
      METHODS: Seven patients with drug-refractory VT of right bundle branch block
      morphology were investigated to identify the arrhythmogenic substrate using three
      dimensional (3-D) electroanatomic endocardial and epicardial mapping. RESULTS: In
      three patients with repetitive monomorphic VT, endocardial and epicardial mapping
      during tachycardia showed a focal pattern with an earliest activation preceding
      the onset of the QRS complex by 20 and 28 ms in the lateral aspect of the
      epicardial outflow tract in two patients and by 24 ms near the posterolateral
      mitral annulus in one patient; in two patients with sustained VT, endocardial
      mapping during tachycardia displayed a focal pattern with a wide breakthrough,
      and epicardial mapping showed a macroreentrant VT with an isthmus located in the
      left anterior wall in one patient and in the left inferolateral wall in the
      other. In the remaining two patients, endocardial and epicardial mapping were
      performed during sinus rhythm. An area with fragmented and late potentials as
      well as low amplitude was only identified in the epicardial left inferolateral
      wall. During tachycardia, a diastolic potential was only recorded on the
      epicardium and coincided with the late potential during sinus rhythm in the same
      area. A focal or linear epicardial irrigated lesion terminated the VT and
      resulted in noninducibility in all seven patients. During a median follow-up of
      16 months, VT recurred in two patients without antiarrhythmic drugs. The
      recurrent VT was successfully reablated in one patient and treated with oral
      amiodarone in the other. CONCLUSION: Subepicardial left focal and macroreentrant
      VT may present as focal origin on endocardial mapping and can only be abolished
      by radiofrequency (RF) applications in the epicardial space.

PMID- 14689120
TI  - Catheter Ablation of Ventricular Fibrillation in Structurally Normal Hearts
      Targeting the RVOT and Purkinje Ectopy.
AB  - Catheter ablation for ventricular fibrillation in structurally normal hearts is
      in its infancy. Recently, catheter ablation of idiopathic ventricular
      fibrillation as well as ventricular fibrillation associated with the long QT and
      Brugada syndromes has been described. This review article is a summary of our
      current understanding of the technique and results of catheter ablation of
      ventricular fibrillation in structurally normal hearts.

PMID- 14689121
TI  - [Cardiac resynchronization therapy-current status and future perspectives].
AB  - BACKGROUND AND AIM: Cardiac resynchronization therapy (CRT) by pacemakers is a
      new therapeutic principle in the treatment of advanced heart failure. It aims to
      correct the intracardiac conduction disturbances that are frequently associated
      with left ventricular dysfunction and thus reduce their negative hemodynamic
      consequences. In early studies on CRT, acute improvement in cardiac hemodynamics
      could be shown. Nowadays it is accepted that cardiopulmonary exercise capacity is
      also improved in the long term with CRT. In addition, reduction of functional
      mitral regurgitation and reverse left ventricular remodeling have been
      demonstrated in the majoriy of patients. The results of recent studies
      demonstrate a reduction in mortality and hospitalizations by CRT. The results of
      these trials have led to an accepted indication for CRT as an adjunct treatment
      in heart failure in the updated US guidelines. However, about 30% of patients
      undergoing device implantation according to currently accepted implant criteria
      will show no substantial improvement with CRT. Therefore, other indicators to
      identify therapy responders must be developed in the future, e.g. by using
      echocardiographic techniques. Moreover, it is yet unclear in how many patients a
      defibrillator backup is necessary for a CRT patient. This article summarizes the
      current status of CRT with regard to indications and clinical results. In
      addition, unresolved issues are discussed and potential developments for the
      future highlighted.

PMID- 14689122
TI  - [Echocardiography in cardiac resynchronization therapy: identification of
      suitable patients, follow-up and therapy optimization].
AB  - BACKGROUND AND AIM: Cardiac resynchronization therapy (CRT) with biventricular
      stimulation is a new therapeutic option for patients with advanced heart failure
      and left ventricular asynchrony. The presence of a left bundle branch block
      morphology in the electrocardiogram is presently the most important selection
      criterion. Transthoracic echocardiography provides important additional
      information on the ventricular contraction sequence and the hemodynamic
      consequences of asynchrony. This may help to identify suitable patients, to
      improve the selection criteria and to optimize CRT during follow-up. This article
      discusses the potential techniques and limitations and provides practical
      guidance for the individual patient follow-up.

PMID- 14689123
TI  - Oxidative stress, antioxidant vitamins, and atherosclerosis. From basic research
      to clinical practice.
AB  - Oxidative stress is involved in the pathogenesis of atherosclerosis, while a
      variety of antioxidants has been used in clinical studies, during the past few
      years, for the prevention and treatment of atherosclerosis. In small clinical
      studies it was found that both vitamins C and E may improve endothelial function
      in patients with risk factors for atherosclerosis such as diabetes mellitus,
      smoking, hypertension, or hypercholesterolemia. However, the initial, hopeful
      reports regarding the beneficial role of antioxidant vitamins against
      atherosclerosis, derived from purely observational studies, were followed by the
      negative results of almost all large randomized trials. Therefore, treatment with
      antioxidant vitamins C and E should not be recommended for the prevention or
      treatment of coronary atherosclerosis. New antioxidant strategies are needed to
      clarify the exact role of antioxidant treatment in coronary atherosclerosis.

PMID- 14689124
TI  - Letter to the Editors: concerning the article "Amyloid of heart and lungs in a
      patient with low output syndrome after coronary artery bypass grafting" by
      Massoudy P, Szabo AK, Dirsch O, et al. Herz 2003;28;453-6.

PMID- 14689125
TI  - Delayed oedema in the pyramidal tracts remote from intracerebral missile path
      following gunshot injury.
AB  - A 60-year-old man developed a severe left hemiparesis and central facial palsy,
      accompanied by somnolence and dysarthria 9 days after a gunshot wound to the
      right temporal region, from which he slowly recovered over 3 months. MRI
      disclosed bilateral oedema of the pyramidal tracts. This was interpreted as a
      consequence of the impact of the pressure wave caused by the bullet, after
      excluding an infectious or vascular cause.

PMID- 14689126
TI  - Acute endovascular treatment of ruptured aneurysms in poor-grade patients.
AB  - We reviewed the 6-month outcome of 45 consecutive patients in poor grade treated
      acutely by coiling after subarachnoid haemorrhage (SAH). About half had a
      favourable outcome, a promising result in accordance with some surgical and
      endovascular reports proposing early aggressive treatment of an aneurysm causing
      SAH. The poor clinical grade, due to parenchyma damage from the SAH, remains the
      main prognostic factor, rebleeding from the untreated aneurysm being only one
      cause of poor outcome. It is therefore difficult to isolate the impact of any
      treatment of the aneurysm on outcome, and unavoidable selection bias may strongly
      influence favourable results. Nevertheless, available evidence and the limited
      invasiveness suggest that acute endovascular treatment is reasonable in these
      patients.

PMID- 14689127
TI  - Respiratory tract infections in general practice: considerable differences in
      prescribing habits between general practitioners in Denmark and Spain.
AB  - OBJECTIVE: The prevalence of antibiotic resistance in a country reflects the
      local consumption of antibiotics. The majority of antibiotics are prescribed in
      general practice and most prescriptions are attributable to treatment of
      respiratory tract infections (RTIs). The aim of this study was to compare general
      practitioners' (GPs') prescribing of antibiotics for respiratory tract infections
      in a country with a high prevalence of antibiotic resistance (Spain) with a
      country with a low prevalence of antibiotic resistance (Denmark). METHODS: A
      group of GPs in Copenhagen and Barcelona registered all contacts ( n=2833) with
      patients with RTIs during a 3-week period between 1 November 2001 and 31 January
      2002. RESULTS: Overall, Spanish GPs treated a higher proportion of patients than
      Danish GPs. After adjusting for unequal distribution of age and sex, we found
      that Spanish GPs prescribed significantly more antibiotics to patients with focus
      of infection in tonsils and bronchi/lungs. Narrow-spectrum penicillin was the
      most used antibiotic in Denmark, representing 58% of all prescriptions issued,
      followed by macrolide and broad-spectrum penicillin. In Spain, prescriptions were
      distributed among a great number of compounds, with broad-spectrum penicillins
      and combinations of amoxicillin plus beta-lactamase inhibitors most frequently
      used. CONCLUSION: The substantial difference in the way GPs manage respiratory
      tract infections in Denmark and Spain cannot be explained by different patterns
      of RTIs in general practice. The discrepancies indicate variations in national
      recommendations, different treatment traditions or different impact of
      pharmaceutical marketing.

PMID- 14689131
TI  - Altered synaptic and electrical properties of lumbar motoneurons in the
      neurological glial mutant taiep rat.
AB  - Maturation and differentiation of electrical properties of neurons and synaptic
      transmission are modulated by neuronal interaction. In vitro experiments have
      shown that these processes also seem to be regulated by signals from non-neuronal
      elements such as glial cells. It is not known, however, whether glial alterations
      in intact neural networks may also affect the maturation of electrical properties
      and synaptic transmission during development. We used the taiep rat, a
      neurological mutant with a progressive demyelination and astrogliosis, as an
      experimental model to study the postnatal development of motoneurons in an
      altered glial environment. Using the patch-clamp technique, we made intracellular
      recording from motoneurons of Rexed's lamina IX in spinal cord slices of neonatal
      rats (postnatal day P4-P10). The electrical properties of normal motoneurons
      changed significantly with age, showing decreasing input resistance (R(in)) and
      increasing membrane capacity (C(m)). The rheobase increased with age, accompanied
      by an increase of the amplitude and a decrease of the duration of action
      potentials (APs). In contrast, mutant neurons showed no age-dependent changes of
      R(in), C(m), or AP characteristics. After blocking inhibitory transmission,
      intralaminar bipolar stimulation elicited, in both control and taiep motoneurons,
      fast glutamatergic excitatory postsynaptic potentials (EPSPs). Two types of taiep
      motoneurons were identified according to the temporal patterns of synaptic
      responses; (1). taiep(SYN) neurons, which showed no significant differences to
      control motoneurons, and (2). taiep(ASYN) neurons, in which the initial EPSP was
      followed by a variable number of delayed, asynchronous EPSP responses (for up to
      300 ms). All these electrophysiological findings suggest that the mutation in
      taiep rats interfered with the development of the electrical properties of
      neurons and with the maturation of synaptic transmission, probably due to
      alterations in the neuron-glia interactions.

PMID- 14689132
TI  - Proposed cortical and sub-cortical contributions to the long-latency stretch
      reflex in the forearm.
AB  - The short- and long-latency (SLSR, LLSR) components of the stretch reflex
      response were investigated in the forearm using a paired transcranial magnetic
      stimulation (TMS)-stretch reflex protocol. Responses to TMS were recorded in the
      flexor and extensor carpi radialis muscles (FCR, ECR) after conditioning with a
      rapid wrist extension movement. The cortical stimuli were timed to elicit a motor
      evoked potential (MEP) at either the SLSR or LLSR onset in the FCR muscle.
      Responses were also collected in TMS-alone and stretch reflex-alone conditions.
      Six intensities of magnetic stimulation were applied in all conditions. In the
      FCR muscle, MEP amplitude when timed to arrive at the LLSR onset was
      significantly greater than the sum of the MEP and stretch reflex responses when
      given separately. MEP amplitudes at the SLSR onset in the FCR muscle and in the
      ECR muscle at both SLSR and LLSR onset were not significantly different from that
      expected from the sum of the two stimuli given separately. This indicates
      heightened corticospinal excitability at a time corresponding to the passage of
      an afferent volley induced by the stretch, and raises the possibility of a
      transcortical loop of the LLSR in the forearm. The extent of MEP facilitation was
      generally consistent across all stimulus intensities tested. A reduced component
      of the LLSR was evident when the stretch response was timed to arrive during the
      silent period following the cortical stimulus, suggesting both cortical and sub
      cortical components to the reflex response.

PMID- 14689133
TI  - Pain differs from non-painful attention-demanding or stressful tasks in its
      effect on postural control patterns of trunk muscles.
AB  - Pain changes postural activation of the trunk muscles. The cause of these changes
      is not known but one possibility relates to the information processing
      requirements and the stressful nature of pain. This study investigated this
      possibility by evaluating electromyographic activity (EMG) of the deep and
      superficial trunk muscles associated with voluntary rapid arm movement. Data were
      collected from control trials, trials during low back pain (LBP) elicited by
      injection of hypertonic saline into the back muscles, trials during a non-painful
      attention-demanding task, and during the same task that was also stressful. Pain
      did not change the reaction time (RT) of the movement, had variable effects on RT
      of the superficial trunk muscles, but consistently increased RT of the deepest
      abdominal muscle. The effect of the attention-demanding task was opposite:
      increased RT of the movement and the superficial trunk muscles but no effect on
      RT of the deep trunk muscles. Thus, activation of the deep trunk muscles occurred
      earlier relative to the movement. When the attention-demanding task was made
      stressful, the RT of the movement and superficial trunk muscles was unchanged but
      the RT of the deep trunk muscles was increased. Thus, the temporal relationship
      between deep trunk muscle activation and arm movement was restored. This means
      that although postural activation of the deep trunk muscles is not affected when
      central nervous system resources are limited, it is delayed when the individual
      is also under stress. However, a non-painful attention-demanding task does not
      replicate the effect of pain on postural control of the trunk muscles even when
      the task is stressful.

PMID- 14689134
TI  - Learning a single limb multijoint coordination pattern: the impact of a
      mechanical constraint on the coordination dynamics of learning and transfer.
AB  - The coordination dynamics of learning and transfer were studied in a single limb
      multijoint task requiring rhythmic elbow and wrist motions. Participants were
      required to learn a continuous 90 degrees relative phase pattern between the
      elbow and wrist such that an angle-angle plot of elbow and wrist motion produced
      a circle with a diameter of 80 degrees. Joint motion was restricted to elbow and
      wrist flexion-extension on the sagittal plane and the to-be-learned 90 degrees
      relative phase pattern was always practiced with the learning arm supine. Cycling
      frequency was controlled by a pacing metronome set at 0.75 Hz. Issues regarding
      effector-independent and effector-specific transfer were addressed with three
      transfer conditions: (1). learning arm prone (LP), (2). non-learning arm supine
      (NS), and (3). non-learning arm prone (NP). Four subjects learned the required
      relative phase (90 degrees ) and amplitude (80 degrees ) pattern with their
      dominant arm and four with their non-dominant arm. The experiment produced three
      main findings with regard to elbow-wrist control processes: First, seven of eight
      participants spontaneously produced a wrist-lagging coordination pattern (wrist
      motion lagged elbow motion) in learning to produce a continuous relative phase
      pattern of 90 degrees between the elbow and wrist. The wrist-lagging pattern may
      emerge as a result of the central nervous system exploiting the transfer of
      angular momentum from the elbow to the wrist as the elbow rotates up and down.
      The influence of interactive torque on elbow-wrist coordination represents an
      important mechanical constraint on the selection of intralimb coordination
      strategies during learning. The transfer conditions revealed that this mechanical
      constraint was effector-independent with regard to ipsilateral limb transfer (LP)
      and contralateral limb transfer (NS and NP). Second, consistent transfer of the
      learned relative phase pattern across ipsilateral and contralateral conditions
      demonstrates an effector-independent representation for this control variable.
      The effector-independent and effector-specific nature of joint amplitude transfer
      was dependent to some degree on learning arm, dominant or non-dominant, and the
      amount of practice, 1 day versus 5 days. Third, learning of the required 90
      degrees relative phase pattern may be characterized as a phase transition leading
      to the formation of a stable attractor in the elbow-wrist coordination landscape.
      The above findings are discussed with respect to motor programming and
      coordination dynamic viewpoints on effector-independent and effector-specific
      aspects of motor equivalence.

PMID- 14689135
TI  - Bimanual coordination: constraints imposed by the relative timing of homologous
      muscle activation.
AB  - It has often been supposed that patterns of rhythmic bimanual coordination in
      which homologous muscles are engaged simultaneously, are performed in a more
      stable manner than those in which the same muscles are activated in an
      alternating fashion. In order to assess the efficacy of this constraint, the
      present study investigated the effect of forearm posture (prone or supine) on
      bimanual abduction-adduction movements of the wrist in isodirectional and non
      isodirectional modes of coordination. Irrespective of forearm posture, non
      isodirectional coordination was observed to be more stable than isodirectional
      coordination. In the latter condition, there was a more severe deterioration of
      coordination accuracy/stability as a function of cycling frequency than in the
      former condition. With elevations in cycling frequency, the performers recruited
      extra mechanical degrees of freedom, principally via flexion-extension of the
      wrist, which gave rise to increasing motion in the vertical plane. The increases
      in movement amplitude in the vertical plane were accompanied by decreasing
      amplitude in the horizontal plane. In agreement with previous studies, the
      present findings confirm that the relative timing of homologous muscle activation
      acts as a principal constraint upon the stability of interlimb coordination.
      Furthermore, it is argued that the use of manipulations of limb posture to
      investigate the role of other classes of constraint (e.g. perceptual) should be
      approached with caution because such manipulations affect the mapping between
      muscle activation patterns, movement dynamics and kinematics.

PMID- 14689136
TI  - Redox state of near infrared spectroscopy-measured cytochrome aa(3) correlates
      with delayed cerebral energy failure following perinatal hypoxia-ischaemia in the
      newborn pig.
AB  - Early detection of delayed cerebral energy failure may be important in the
      prevention of reperfusion injury of the brain after severe perinatal hypoxia
      ischaemia (HI). This study investigated whether monitoring of the redox state of
      cytochrome aa(3) (Cytaa(3)) with near infrared spectroscopy (NIRS) after severe
      perinatal asphyxia may allow us to detect early a compromised energy metabolism
      of the developing brain. We therefore correlated serial Cytaa(3) measurements (to
      estimate mitochondrial oxygenation) simultaneously with the (31)phosphorous
      magnetic resonance spectroscopy ((31)P-MRS)-measured phosphocreatin/inorganic
      phosphate (PCr/Pi) ratio (to estimate cerebral energy reserve) in newborn piglets
      before and after severe hypoxia-ischaemia. The animals were treated upon
      reperfusion with either allopurinol, deferoxamine, or 2-iminobiotin or with a
      vehicle to reduce post-HI reperfusion injury of the brain. Four sham-operated
      piglets served as controls. Before HI, the individual Cytaa(3) values ranged
      between -0.02 and 0.71 micromol/L (mean value: -0.07) relative to baseline. The
      pattern over post-HI time of the vehicle-treated animals was remarkably different
      from the other groups in as far Cytaa(3) became more oxidised from 3 h after
      start of HI onwards (increase of Cytaa(3) as compared with baseline), whereas the
      other groups showed a significant reduction over time (decrease of Cytaa(3) as
      compared with baseline: allopurinol and deferoxamine) or hardly any change (2
      iminobiotin and sham-operated piglets). Vehicle-treated piglets showed a
      significant reduction in PCr/Pi at 24 h after start of HI, but the cerebral
      energy state was preserved in 2-iminobiotin-, allopurinol- and deferoxamine
      treated piglets. With severe reduction in PCr/Pi-ratio, major changes in the
      redox-state of Cytaa(3) also occurred: Cytaa(3) was mostly either in a reduced
      state (down to -6.45 micromol/L) or in an oxidised state (up to 6.84 micromol/L)
      at these low PCr/Pi ratios. The positive predictive value (PPV) of Cytaa(3) to
      predict severe reduction of the PCr/Pi ratio was 42%; the negative PPV was 87%. A
      similar relation was found for Cytaa(3) with histologically determined loss of
      neurons.

PMID- 14689137
TI  - Active eye fixation performance in 940 young men: effects of IQ, schizotypy,
      anxiety and depression.
AB  - A total of 940 young men performed a task in which they actively maintained
      fixation for 50 s in three conditions: a). on a visual target, b). on a visual
      target while distracting targets appeared briefly on the periphery and c). with
      no visual target present. The same individuals completed psychometric evaluation
      tests measuring IQ, schizotypy and current state-dependent psychopathology. The
      proportion of fixation time decreased and saccade frequency increased in
      condition b compared wih condition a, and sequentially in condition c compared
      with condition b. A trend towards a decrease in proportion of fixation time and
      increase in saccade frequency was found as the subjects maintained fixation
      during the task and this time-dependent deterioration of performance was again
      most pronounced in condition c, less so in condition b and absent in condition a.
      Psychometric test scores were significantly correlated with fixation performance
      in the population. Worse performance in all three fixation conditions was
      observed for individuals with lower IQ scores. A deterioration of fixation
      performance with time in condition b was correlated with disorganization
      characteristics of schizotypy, suggesting that these individuals had difficulty
      maintaining active fixation in the presence of increased inhibitory load. A
      connection of such a difficulty with the frontal lobes and their role in the
      control of voluntary inhibitory functions is discussed.

PMID- 14689138
TI  - Temporospatial properties of the effects of bottom-up attention on smooth pursuit
      initiation in humans.
AB  - We examined the temporal and spatial properties of the effects of target saliency
      on the initiation of smooth pursuit eye movement in humans. Visual stimuli
      consisted of random dots projected on a large-field screen. During a fixation
      period, a cluster of dots (2 x 2 deg) was blinked (turned off for a short period)
      to make that region stand out from the remaining background and serve as a cue.
      After a delay (cue lead time), a cluster of dots (2 x 2 deg) started to move as a
      pursuit target. The target and cue were presented at either identical or
      different locations so that the subject could not predict the target location
      from the cue location. We examined the time course of the effect of the cue on
      pursuit initiation by changing the cue lead time. In half of the trials, the cue
      and target locations were identical, and in the other trials, they were not
      identical. There was a clear effect of the cue only for the trials where the cue
      and target locations were identical. The effect of the cue increased as cue lead
      time increased, peaked at approximately 160 ms, and then decreased. We also
      examined the spatial extent of the effect of the cue by varying the distance
      between the target and the cue. The largest effect was observed when the cue and
      the target were presented at the same location. Facilitating effects were
      observed when the target and the cue were presented in the same hemifield but not
      when presented in the opposite hemifield.

PMID- 14689139
TI  - Identification of dorsal root ganglion neurons that innervate the common bile
      duct of rats.
AB  - Pain originating in the bile duct is common and many patients who have suffered
      from it report that it is one of the most intense forms of pain that they have
      experienced. Many uncertainties remain about the mechanisms underlying pain
      originating in the bile duct. For example, the dorsal root ganglion (DRG) neurons
      that give rise to the sensory innervation of the common bile duct (CBD) have not
      been identified and examined in any species. The goal of the present study was to
      determine the number, distribution, and size of DRG neurons that innervate the
      CBD in rats. Injections of WGA-HRP or CTB-HRP were restricted to the lumen of the
      bile duct. Injections of WGA-HRP labeled a mean number of about 500 DRG neurons
      bilaterally throughout all thoracic and upper lumbar levels. Injections of CTB
      HRP labeled smaller numbers of DRG neurons. Application of colchicine onto the
      surface of the CBD reduced the number of cells labeled following injections of
      WGA-HRP into the lumen of the CBD by roughly 86%, suggesting that tracer had not
      spread in large amounts out of the CBD and labeled afferent fibers in other
      tissues. Approximately 85% of the neurons labeled with WGA-HRP had cell bodies
      that were classified as small; the remainder were medium in size. Injections of
      CTB-HRP labeled cell bodies of varying sizes, including a few large diameter cell
      bodies. These results indicate that a large number of primarily small DRG cells,
      located bilaterally at many segmental levels, provide a rich innervation of the
      common bile duct.

PMID- 14689140
TI  - Latency and accuracy of saccades to somatosensory targets.
AB  - PURPOSE: To examine the accuracy and latency of reflexive saccades to vibratory
      stimulation of the fingertips made by normal human subjects and to compare the
      findings to those of visually guided saccades. METHODS: Eye movements were
      recorded using infrared oculography. Stimuli were presented via an array of
      audiometric bone vibrator transducers driven at 250 Hz and positioned at eye
      level in a darkened room. Target locations were at 0 and +/-5, 10, and 15 deg.
      Visual stimuli were green LEDs. Saccades were analysed interactively off-line and
      latency and amplitude measured for both types of saccade. RESULTS: Saccades to
      tactile stimuli had longer latencies and showed less accurate final eye positions
      than those to equivalent visual targets; they were unaffected by subject age.
      Error magnitude for the tactile saccades increased monotonically with increasing
      target eccentricity; because the fingers remained in a fixed position throughout
      the testing, this also meant that error was lowest for the thumb and increased
      with progression outwards towards the ring finger. Visually guided refixations
      were accurate and differed less than 0.2 deg across target locations. Subject age
      had no effect on performance. CONCLUSIONS: Human subjects may make relatively
      accurate refixations to tactile targets in the absence of visual cues, but only
      to certain locations/fingers; others were localised very poorly. Further studies
      are needed to determine whether finger selection or target location is the
      primary determinant of accuracy in this task.

PMID- 14689141
TI  - Grip responses to object load perturbations are stimulus and phase sensitive.
AB  - Responses to load changes of a held object that challenge grasp stability are
      known to be adept and fast, but the responses to changes in load where grasp
      stability is not challenged are not well understood. In order to compare
      responses to these functionally opposite perturbations, the grasp response to
      increases and decreases in the load of a held object was examined. A pulling
      force used to create object load was abruptly altered so that it felt lighter
      (decreased load) or felt heavier (increased load). The perturbation occurred
      either during movement of the object (lift) or when the object was held steady
      (hold). Grip force modulation was earlier, larger, had a faster maximum rate and
      a smaller change in relative safety margin when load increased. Also, the grip
      force modulation was earlier, larger, had a faster maximum grip force rate and a
      smaller change in relative safety margin when the perturbation occurred during
      active lift. In the decreased loading condition, participants were not required
      to make a grip force adjustment to maintain grip. Interestingly, participants
      chose to make the adjustment (decreasing grasp force), albeit more slowly. During
      the lift phase, the nature of the task is more dynamic and the resulting
      additional mechanical stimulation may have lead to a facilitated response. The
      results point to the greater functional significance of increasing load for grip
      force modulation and the potential for greater sensory or motor facilitation
      during dynamic lifting.

PMID- 14689142
TI  - Unconscious perception of non-threatening facial emotion in parietal extinction.
AB  - The success of humans as social animals relies heavily on our ability to perceive
      the emotional expressions conveyed by others' faces. Functional brain imaging has
      shown that expressions of fear and anger selectively activate the amygdala, even
      when the faces conveying the emotion are presented briefly and masked to prevent
      conscious perception (Morris et al. 1998; Whalen et al. 1998). Such results
      suggest that facial emotions signalling potential threat can be extracted rapidly
      and automatically by the human visual system, in the absence of conscious face
      perception. Here we asked whether a patient with spatial extinction, a profound
      disorder of perception due to right parietal lobe damage, would be sensitive to
      non-threatening (happy and sad) emotional expressions of faces that are not
      consciously perceived. We show that the emotion conveyed by an extinguished face
      in the contralesional hemifield can influence judgements of the emotion of a
      subsequent target face presented foveally. The finding of significant affective
      priming from extinguished faces fits with the proposal that facial emotion can be
      processed in the absence of conscious perception, and that preserved limbic and
      inferotemporal structures retain privileged access to the emotional content of
      'unseen' faces.

PMID- 14689143
TI  - Tactile feedback contributes to consistency of finger movements during typing.
AB  - Touch typing movements are typically too brief to use on-line feedback. Yet,
      previous studies have shown that blocking tactile feedback of the fingertip of
      typists leads to an increase in typing errors. To determine the contribution of
      tactile information to rapid fine motor skills, we analyzed kinematics of the
      right index finger during typing with and without tactile feedback. Twelve expert
      touch typists copy-typed sentences on a computer keyboard without vision of their
      hands or the computer screen. Following control trials, their right index
      fingertip was anesthetized, and sentences were typed again. The movements of the
      finger were recorded with an instrumented glove and electromagnetic position
      sensor. During anesthesia, typing errors of that finger increased sevenfold.
      While the inter-keypress timing and average kinematics were unaffected, there was
      an increase in variability of all measures. Regression analysis showed that
      endpoint variability was largely accounted for by start location variability. The
      results suggest that tactile cues provide information about the start location of
      the finger, which is necessary to perform typing movements accurately.

PMID- 14689145
TI  - Foot equilibrium position controls partition of voluntary command to antagonists
      during foot oscillations.
AB  - During low-frequency (< 1.5 Hz) voluntary oscillations of the foot, placed on a
      rotating platform, onset of the Tibialis Anterior (TA) EMG paradoxically phase
      lags the onset of dorsiflexion, suggesting that initial dorsiflexion is sustained
      by recoil of elastic structures that were stretched during plantarflexion. It is
      argued that the lag would disappear if the EMG onset were referred to the foot
      passive equilibrium position rather than to the movement onset. This hypothesis
      was tested in ten subjects who, after assessment of foot equilibrium position,
      voluntarily oscillated their foot at various frequencies (0.2-3 Hz) over three
      angular ranges: a mid range (foot crossing the equilibrium symmetrically), a high
      range (whole excursion above equilibrium) and a low range (whole excursion below
      equilibrium). In the mid range, phase relations were measured between the
      crossing of equilibrium position and the onset of the TA EMG during dorsiflexion
      or the onset of Soleus EMG during plantarflexion. In both cases, the paradoxical
      lag of EMG on movement was absent, phase curves started around zero and could be
      well fitted by a second order model. Phase curves with similar features were also
      obtained in the high and low ranges (no crossing of equilibrium) but correlating
      the onset of the EMG burst to the onset of the related movement. Altogether,
      these findings show that in all ranges of the joint excursion, the homology is
      between the EMG onset and the moment when the foot draws away from equilibrium.
      Based on the observed pattern of muscular activation, we suggest that voluntary
      foot oscillation in any movement range is sustained by one sinusoidal central
      command that, when equilibrium is crossed, is clipped in two half-waves
      reciprocally distributed to the couple of antagonist muscles. A simple neural
      circuit for this operation is proposed.

PMID- 14689144
TI  - Ultrastructural observations of efferent terminals in the crista Ampullaris of
      the toadfish, opsanus tau.
AB  - The present study was conducted to visualize the ultrastructural features of
      vestibular efferent boutons in the oyster toadfish, Opsanus tau. The crista
      ampullaris of the horizontal semicircular canal was processed for and examined by
      routine transmission electron microscopy. The results demonstrate that such
      boutons vary in size and shape, and contain a heterogeneous population of lucent
      vesicles with scattered dense core vesicles. Efferent contacts with hair cells
      are characterized by local vesicle accumulations in the presynaptic terminal and
      a subsynaptic cistern in the postsynaptic region of the hair cell. Serial
      efferent to hair cell to afferent synaptic arrangements are common, particularly
      in the central portion of the crista. However, direct contacts between efferent
      terminals and afferent neurites were not observed in our specimens. The existence
      of serial synaptic contacts, often with a row of vesicles in the efferent boutons
      lining the efferent-afferent membrane apposition, suggests that the efferent
      influence on the crista may involve both synaptic and nonsynaptic, secretory
      mechanisms. Further, it is suggested that differences in more subtle aspects of
      synaptic architecture and/or transmitter and receptor localization and
      interaction may render the efferent innervation of the peripheral crista less
      effective in influencing sensory processing.

PMID- 14689151
TI  - Ultrasonic agitation in microchannels.
AB  - This paper describes an acoustic method for inducing rotating vortex flows in
      microchannels. An ultrasonic crystal is used to create an acoustic standing wave
      field in the channel and thus induce a Rayleigh flow transverse to the laminar
      flow in the channel. Mixing in microchannels is strictly diffusion-limited
      because of the laminar flow, a transverse flow will greatly enhance mixing of the
      reactants. This is especially evident in chemical microsystems in which the
      chemical reaction is performed on a solid phase and only one reactant is actually
      diffusing. The method has been evaluated on two different systems, a mixing
      channel with two parallel flows and a porous silicon micro enzyme reactor for
      protein digestion. In both systems a significant increase of the mixing ratio is
      detected in a narrow band of frequency for the actuating ultrasound.

PMID- 14689146
TI  - Trunk recruitment during spoon use in tetraparetic cerebral palsy.
AB  - In the present study we investigated the extent to which individuals suffering
      from spastic tetraparesis as a consequence of cerebral palsy tune their trunk
      involvement to accuracy demands in a spoon-handling task. Twenty-two participants
      (ten adolescents with spastic tetraparesis and 12 control participants) had to
      transport a spoon filled with water or sugar to a small or a large bowl that was
      placed within reach. Even though trunk displacement was larger in the
      tetraparetic participants than it was in the control participants, the effects of
      the imposed accuracy constraints were remarkably similar. Participants in both
      groups increased trunk displacement with increasing precision requirements.
      Furthermore, in both groups the largest trunk involvement was found in the
      initial and final part of the substance-transporting phase, when wrist velocity
      was lowest. We propose several explanations for these findings and conclude that
      the large trunk involvement in individuals with tetraparetic cerebral palsy
      should, in any case, not be regarded as a primary symptom of the disorder, but
      rather as an adaptive reaction to increased task demands.

PMID- 14689152
TI  - Size-based analysis of incinerator fly ash using gravitational SPLITT
      fractionation, sedimentation field-flow fractionation, and inductively coupled
      plasma-atomic emission spectroscopy.
AB  - Fly ash has been regarded as hazardous because of its high adsorption of toxic
      organic and/or inorganic pollutants. Fly ash is also known to have broad
      distributions of different chemical and physical properties, such as size and
      density. In this study, fly ash emitted from a solid waste incinerator was pre
      fractionated into six sub-populations by use of gravitational SPLITT
      fractionation (GSF). The GSF fractions were then analyzed by sedimentation field
      flow fractionation (SdFFF) and ICP-AES. SdFFF analysis showed the fly ash has a
      broad size distribution ranging from a few nanometers up to about 50 microm.
      SdFFF results were confirmed by electron microscopy. Inductively coupled plasma
      atomic emission spectroscopy (ICP-AES) analysis of the GSF fractions showed the
      fly-ash particles contain a variety of inorganic elements including Ca, Si, Mg,
      Fe, and Pb. The most abundant in fly ash was Ca, followed by Si then Mg. No
      correlations were found between trace element concentration and particle size.

PMID- 14689153
TI  - Doehlert matrix for optimisation of procedure for determination of nickel in
      saline oil-refinery effluents by use of flame atomic absorption spectrometry
      after preconcentration by cloud-point extraction.
AB  - This paper proposes a preconcentration procedure for determination of nickel in
      saline aqueous waste samples by flame atomic absorption spectrometry (FAAS). It
      is based on cloud-point extraction of nickel(II) ions as 2-(5-bromo-2-pyridylazo)
      5-diethilaminophenol (Br-PADAP) complexes using octylphenoxypolyethoxyethanol
      (Triton X-114) as surfactant. The optimisation step was performed using a four
      variable Doehlert design, involving the factors centrifugation time (CT) of
      system after addition of surfactant, solution pH, methanol volume (MV) added at
      micellar phase, and buffer concentration (BC). The analytical response used was
      absorbance, after volume correction. Using the established experimental
      conditions in the optimisation step the procedure enables nickel determination
      with a detection limit (3 delta/ S) of 0.2 microg L(-1), quantification limit (10
      delta/ S) of 0.7 microg L(-1), and precision, calculated as relative standard
      deviation ( RSD) of 4.7 ( n=8) and 3.5% ( n=8) for nickel concentration of 1 and
      5 microg L(-1), respectively. The preconcentration factor, determined from the
      ratio of the slopes of the analytical curves with and without preconcentration,
      is 74. The recovery achieved for nickel determination in the presence of several
      cations demonstrated that this procedure could be applied for analysis of water
      samples. The robustness was checked by using saturated fractional factorial
      designs, centred on the established experimental conditions in the optimisation
      step. The results of these tests demonstrated that the variables centrifugation
      time and buffer concentration are robust for modification by 10% and that
      solution pH and methanol volume are robust for 5%. Accuracy was evaluated by
      using the certified material reference SLEW-3 estuarine water for trace metals.
      The procedure was used for determination of nickel in saline effluents from oil
      refinery samples. Recovery results (95-104%) indicate that the procedure has
      satisfactory accuracy for nickel determination in these samples.

PMID- 14689154
TI  - Simple and selective method for determination of iodide in pharmaceutical
      products by flow injection analysis using the iodine-starch reaction.
AB  - This work exploited the well-known iodine-starch reaction for development of a
      simple flow-injection (FI) method for determination of iodide in pharmaceutical
      samples. Iodide in an injected zone was oxidized to iodine. A gas diffusion unit
      enables selective permeation of iodine through a hydrophobic membrane. Detection
      was made very selective for elemental iodine by employing formation of the I(3)(
      )-starch complex. The detection limit (3 S/ N) of the system was 1 mg I L(-1).
      For a liquid patent medicine used for asthma treatment we suggested modification
      of the system. Direct injection of this sample, which contains a particularly
      high concentration level of iodide (ca. 9000 mg I L(-1)), can be achieved by
      coupling a dialysis unit to the FI system. This has increased the working range
      to 6000-10,000 mg I L(-1) without employing complicated nanoliter injection.

PMID- 14689155
TI  - Cloned plasmid DNA fragments as calibrators for controlling GMOs: different real
      time duplex quantitative PCR methods.
AB  - Analytical real-time PCR technology is a powerful tool for implementation of the
      GMO labeling regulations enforced in the EU. The quality of analytical
      measurement data obtained by quantitative real-time PCR depends on the correct
      use of calibrator and reference materials (RMs). For GMO methods of analysis, the
      choice of appropriate RMs is currently under debate. So far, genomic DNA
      solutions from certified reference materials (CRMs) are most often used as
      calibrators for GMO quantification by means of real-time PCR. However, due to
      some intrinsic features of these CRMs, errors may be expected in the estimations
      of DNA sequence quantities. In this paper, two new real-time PCR methods are
      presented for Roundup Ready soybean, in which two types of plasmid DNA fragments
      are used as calibrators. Single-target plasmids (STPs) diluted in a background of
      genomic DNA were used in the first method. Multiple-target plasmids (MTPs)
      containing both sequences in one molecule were used as calibrators for the second
      method. Both methods simultaneously detect a promoter 35S sequence as GMO
      specific target and a lectin gene sequence as endogenous reference target in a
      duplex PCR. For the estimation of relative GMO percentages both "delta C(T)" and
      "standard curve" approaches are tested. Delta C(T) methods are based on direct
      comparison of measured C(T) values of both the GMO-specific target and the
      endogenous target. Standard curve methods measure absolute amounts of target
      copies or haploid genome equivalents. A duplex delta C(T) method with STP
      calibrators performed at least as well as a similar method with genomic DNA
      calibrators from commercial CRMs. Besides this, high quality results were
      obtained with a standard curve method using MTP calibrators. This paper
      demonstrates that plasmid DNA molecules containing either one or multiple target
      sequences form perfect alternative calibrators for GMO quantification and are
      especially suitable for duplex PCR reactions.

PMID- 14689156
TI  - Filling the AOAC triangle with food-matrix standard reference materials.
AB  - Well-characterized reference materials are needed by laboratories in the food
      testing and nutrition communities to facilitate compliance with nutritional
      labeling laws, to provide traceability for food exports needed for acceptance in
      many foreign markets, and to improve the accuracy of nutrition information that
      is provided to assist consumers in making sound dietary choices. As a result of
      the enactment of the Nutrition Labeling and Education Act of 1990 and the Infant
      Formula Act of 1980, the National Institute of Standards and Technology (NIST)
      has developed a suite of food-matrix Standard Reference Materials (SRMs)
      characterized for nutrient concentrations. These include SRM 1544 Fatty Acids and
      Cholesterol in a Frozen Diet Composite, SRM 1546 Meat Homogenate, SRM 1548a
      Typical Diet, SRM 1566b Oyster Tissue, SRM 1846 Infant Formula, SRM 1946 Lake
      Superior Fish Tissue, SRM 2383 Baby Food Composite, SRM 2384 Baking Chocolate,
      SRM 2385 Spinach, and SRM 2387 Peanut Butter. Many of these materials were
      developed at the request of the food industry to populate a nine-sectored fat
      protein-carbohydrate triangle developed by AOAC International. With the
      completion of SRM 2387, SRMs representing each sector of the triangle are now
      available. These food-matrix reference materials are intended primarily for
      validation of analytical methods for the measurement of proximates, fatty acids,
      vitamins, minerals, and so on in foods of similar composition. They may also be
      used as "primary control materials" in the value-assignment of in-house,
      secondary, control materials to confirm accuracy as well as to establish
      traceability to NIST.

PMID- 14689159
TI  - Multianalyte determination of different classes of pesticides (acidic, triazines,
      phenyl ureas, anilines, organophosphates, molinate and propanil) by liquid
      chromatography-electrospray-tandem mass spectrometry.
AB  - This work describes the optimization of a liquid chromatography-electrospray
      tandem mass spectrometry (LC-ESI-MS-MS) method for the multianalyte determination
      of twenty pesticides, selected based on current regulations and extent of use.
      Chromatographic separation was carried out on a Purospher STAR RP-18e column
      using gradient acetonitrile-water as mobile phase. Triazines, phenylureas,
      organophosphates, anilines, and molinate were determined in the positive
      ionization mode, and acidic pesticides and propanil in the negative ion mode. Two
      different precursor ion-product ion transitions were selected for each analyte
      and monitored under time scheduled multiple reaction monitoring (MRM) conditions.
      The optimized method was shown to be linear in the range 1 to 1000 ng/mL with
      correlation coefficients higher than 0.99 for all but one (diazinon) of the
      analytes, very sensitive (with limits of detection between 0.010 and 4.528
      ng/mL), and repeatable (with relative standard deviations, calculated from the
      replicate analysis of standard mixtures, lower than 14%). The present work was
      also devoted to the elucidation of the structures of the principal fragment ions
      obtained after collision-induced dissociation of the pesticides investigated, an
      aspect often overlooked in the literature.

PMID- 14689160
TI  - Liquid chromatography-mass spectrometry: reaching maturity rapidly.

PMID- 14689161
TI  - Evaluation of three calibration methods to compensate matrix effects in
      environmental analysis with LC-ESI-MS.
AB  - In quantitative analysis of environmental samples using high-performance liquid
      chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS) one of the
      major problems is the suppression or, less frequently, the enhancement of the
      analyte signals in the presence of matrix components. Standard addition is the
      most suitable method for compensating matrix effects, but it is time-consuming
      and laborious. In this study we compare the potential of three calibration
      approaches to compensate matrix effects that occurred when seven analytes
      (naphthalene sulfonates) were quantified in time series samples of waters with
      different matrices (untreated and treated industrial wastewater). The data
      obtained by external calibration, internal calibration with one standard, and
      external sample calibration (corresponding to matrix-matched calibration) were
      compared with those obtained by standard addition. None of the three approaches
      were suitable for a sample series of highly loaded, untreated wastewater with
      highly variable matrix. For less heavily loaded and less variable samples
      (treated wastewater effluents), the external sample calibration provided
      reasonable results for most analytes with deviations mostly below 25% as compared
      to standard addition. External sample calibration can be suitable to compensate
      matrix effects from moderately loaded samples with more uniform matrices, but it
      is recommended to verify this for each sample series against the standard
      addition approach.

PMID- 14689162
TI  - Diazepam produces disinhibitory cognitive effects in male volunteers.
AB  - RATIONALE: Diazepam has well known amnestic and sedative effects but effects on
      fronto-executive function remain largely uninvestigated, especially on
      neuropsychologically validated tests of risk taking and orbitofrontal cortex
      function. OBJECTIVES: We aimed to determine the impact of diazepam on a variety
      of executive tasks. METHODS: The effects of 5, 10 and 20 mg of diazepam on a
      battery of neuropsychological tests were investigated using a randomised, double
      blind, placebo-controlled design. Seventy-five adult men were recruited. The
      Rogers et al. (1999b) test of risk-taking was given along with tasks from the
      CANTAB battery. RESULTS: Diazepam impaired performance on the Tower of London
      test of planning, without influencing visual pattern recognition memory. Subjects
      who had taken diazepam made more risky choices on the risk-taking task. On two
      speeded reaction time tasks diazepam impaired discrimination sensitivity and
      increased the bias to respond. CONCLUSIONS: In contrast to the well-known
      sedative effects of diazepam, we demonstrate disinhibitory effects on two speeded
      reaction time tasks. Our results show that diazepam can impair performance on
      reaction time tasks both by impairing sensitivity and by increasing the bias to
      respond. Furthermore diazepam impaired performance on tests of planning and risky
      decision making that depend predominantly on dorsolateral and orbitofrontal
      regions of the prefrontal cortex, respectively.

PMID- 14689164
TI  - Comparative responses of three rat strains (DA/Han, Sprague-Dawley and Wistar) to
      treatment with environmental estrogens.
AB  - The rat uterotrophic assay is a widely used screening test for the detection of
      estrogenic, endocrine-disrupting chemicals. Although much attention has been paid
      to identifying protocol variables and reproducibility between laboratories the
      question whether toxicodynamic and toxicokinetic variations of different strains
      may affect their sensitivity to estrogenic stimuli has been rarely addressed. We
      have compared the estrogenic activity of the environmental chemicals genistein
      (GEN), bisphenol A (BPA) and p- tert-octylphenol (OCT) in DA/Han (DA), Sprague
      Dawley (SD) and Wistar (WIS) rats after repeated oral application. Rats were
      treated per os for 3 days with different doses of these weakly estrogenic
      compounds and the potent reference estrogen ethinylestradiol (EE). Then uterine
      wet weight, thickness of the uterine epithelium, uterine gene expression of
      clusterin (CLU), and thickness of the vaginal epithelium were examined as
      parameters for estrogenic potency of the test compounds in the three strains of
      rats. The uterotrophic response to treatment with BPA, OCT and GEN was similar in
      the three strains, and allowed us to rank them as GEN being more potent than OCT,
      and BPA being the weakest estrogen. This was confirmed by analysis of other
      biological endpoints, despite some differences in the magnitude of their response
      among strains and to distinct compounds. For instance, the uterus wet weight
      response to EE treatment indicated lower sensitivity of SD rats than that of DA
      and WIS rats, but this was not observed for responses of the uterine or vaginal
      epithelium. Moreover, blood concentrations were assessed at the time of killing
      and related to biological responses: plasma levels of total and unconjugated BPA
      and GEN depended upon the dose administered and varied to some extent within
      treatment groups and among the three rat strains. However, there was no good
      correlation in the three strains between individual compound concentrations
      analysed 24 h after the last dose and the uterotrophic wet weights. Summarising
      our results, we conclude that the sensitivity of various biological endpoints can
      differ slightly between strains of rats. On the other hand, our data demonstrate
      that the choice of the rat strain does not lead to pronounced differences in the
      evaluation of estrogenic activities of chemicals, especially when different
      biological endpoints are included in the analysis.

PMID- 14689165
TI  - The effect of FITA mutations on the symbiotic properties of Sinorhizobium fredii
      varies in a chromosomal-background-dependent manner.
AB  - nodD1 of Sinorhizobium fredii HH103, which is identical to that of S. fredii
      USDA257 and USDA191, repressed its own expression. Spontaneous flavonoid
      independent transcription activation (FITA) mutants of S. fredii HH103 M (=HH103
      RifR pSym::Tn 5-Mob) showing constitutive expression of nod genes were isolated.
      No differences were found among soybean cultivar Williams plants inoculated with
      FITA mutants SVQ250 or SVQ253 or with the parental strain HH103M. Soybean plants
      inoculated with mutant SVQ255 formed more nodules, and those inoculated with
      mutant SVQ251 had symptoms of nitrogen starvation. Sequence analyses showed that
      all of the FITA mutants carried a point mutation in their nodD1 coding region.
      Mutants SVQ251 and SVQ253 carried the same mutation, but only the former was
      symbiotically impaired, which indicated the presence of an additional mutation
      elsewhere in the genome of mutant SVQ251. Mutants SVQ251 and SVQ255 were
      outcompeted by the parental strain for nodulation of soybean cultivar Williams.
      The symbiotic plasmids of mutants SVQ251 and SVQ255 (pSym251 and pSym255,
      respectively) and that (pSymHH103M) of the parental strain were transferred to
      pSym-cured derivatives of S. fredii USDA192 and USDA193 (USDA192C and USDA193C,
      respectively). Soybean responses to inoculation with S. fredii USDA192C and
      USDA193C transconjugants carrying pSym251 and pSymHH103M were not significantly
      different, whereas more nodules were formed after inoculation with
      transconjugants carrying pSym255. Only transconjugant USDA192C(pSym255) produced
      a significant increase in soybean dry weight.

PMID- 14689166
TI  - Substrate specificities and electron paramagnetic resonance properties of
      benzylsuccinate synthases in anaerobic toluene and m-xylene metabolism.
AB  - The anaerobic degradation pathways of toluene and m-xylene are initiated by
      addition of a fumarate cosubstrate to the methyl group of the hydrocarbon,
      yielding (R)-benzylsuccinate and (3-methylbenzyl)succinate, respectively, as
      first intermediates. These reactions are catalyzed by a novel glycyl-radical
      enzyme, (R)-benzylsuccinate synthase. Substrate specificities of benzylsuccinate
      synthases were analyzed in Azoarcus sp. strain T and Thauera aromatica strain
      K172. The enzyme of Azoarcus sp. strain T converts toluene, but also all xylene
      and cresol isomers, to the corresponding succinate adducts, whereas the enzyme of
      T. aromatica is active with toluene and all cresols, but not with any xylene
      isomer. This corresponds to the capabilities of Azoarcus sp. strain T to grow on
      either toluene or m-xylene, and of T. aromatica to grow on toluene as sole
      hydrocarbon substrate. Thus, differences in the substrate spectra of the
      respective benzylsuccinate synthases of the two strains contribute to utilization
      of different aromatic hydrocarbons, although growth on different substrates also
      depends on additional determinants. We also provide direct evidence by electron
      paramagnetic resonance (EPR) spectroscopy that glycyl radical enzymes
      corresponding to substrate-induced benzylsuccinate synthases are specifically
      detectable in anoxically prepared extracts of toluene- or m-xylene-grown cells.
      The presence of the EPR signals and the determined amount of the radical are
      consistent with the respective benzylsuccinate synthase activities. The
      properties of the EPR signals are highly similar to those of the prototype glycyl
      radical enzyme pyruvate formate lyase, but differ slightly from previously
      reported parameters for partially purified benzylsuccinate synthase.

PMID- 14689167
TI  - Interjoint coordination in lower limbs in patients with a rupture of the anterior
      cruciate ligament of the knee joint.
AB  - Previous studies of movement kinematics in patients with a ruptured anterior
      cruciate ligament (ACL) have focused on changes in angular displacement in a
      single joint, usually flexion/extension of the knee. In the present study, we
      investigated the effect of an ACL injury on the overall limb interjoint
      coordination. We asked healthy and chronic ACL-deficient male subjects to perform
      eight types of movements: forward squats, backward squats, sideways squats,
      squats on one leg, going up a step, going down a step, walking three steps, and
      stepping in place. Depending on the movement concerned, we applied principal
      component (PC) analysis to 3 or 4 degrees of freedom (DFs): thigh
      flexion/extension, knee flexion/extension, ankle flexion/extension, thigh
      abduction/adduction. The first three DFs were investigated in all movements. PC
      analysis identifies linear combinations of DFs. Movements with a fixed ratio
      between DFs are thus described by only one PC or synergy. PCs were computed for
      the entire movement as well as for the period of time when the foot was in
      contact with the ground. For both the control and the injured groups, two
      synergies (PC vectors) usually accounted for more than 95% of the DFs' angular
      excursions. It was possible to describe 95-99% of some movements using only one
      synergy. Compared to control subjects, injured subjects employed different
      synergies for going up a step, walking three steps, squatting sideways, and
      squatting forward, both in the injured and uninjured legs. Those movements may
      thus be more indicative of injury than other movements. Although ACL-deficiency
      did not increase asymmetry (angle between the PCs of the same movement performed
      on the right and the left sides), this result is not conclusive because of the
      comparatively low number of subjects who participated in the study. However, the
      finding that synergies in both legs of patients were different from those in
      control subjects for going up a step and walking three steps suggests that
      interjoint coordination was affected for both legs, so that the asymmetry index
      might have been preserved despite the injury. There was also a relationship
      between the asymmetry index for squatting on one leg, squatting forward, walking
      three steps and some of the outcomes of the knee injury and osteoarthritis
      outcome score (pain, symptoms, activities of daily living, sport and recreation
      function, and knee-related quality of life). This suggests that significant
      differences in the asymmetry index could be obtained if more severely-injured
      patients participated in this study. It is possible that subjects compensated for
      their mechanical deficiencies by modifying muscle activation patterns. Synergies
      were not only modified in injured subjects, but also rearranged: the percentage
      of movement explained by the first PC was different for the injured and/or
      uninjured legs of patients, as compared to the legs of the control group, for
      going up a step, going down a step, walking three steps, and squatting forward.
      We concluded that the analysis of interjoint coordination may be efficient in
      characterizing motor deficits in people with knee injuries.

PMID- 14689169
TI  - Boundary conditions at the tendon-bone interface.
AB  - The reconstruction of a tendon-bone interface, as in rotator-cuff repairs,
      remains a challenging surgical problem. There is however, little data to show
      what effect joint position or repair loading under physiological conditions have
      on the repaired tendon-bone interface. A change in the amount of contact area or
      load at the tendon-bone interface may influence healing. In this study we
      investigated the effect of limb position and boundary conditions on the tendon
      bone interface in an in vitro rabbit tendon-bone repair model using both unlinked
      and linked suture repairs.

PMID- 14689168
TI  - A new rigid biodegradable anchor for meniscus refixation: biomechanical
      evaluation.
AB  - All-inside repair devices have been developed to overcome the disadvantages of
      conventional suture techniques (such as vein and nerve damage and increased OR
      time). The Contour Meniscus Arrow is a second generation of the first
      biodegradable all-inside implant, the Meniscus Arrow. The aim of this study was
      to compare the biomechanical properties of the Contour Meniscus Arrow to the
      first-generation Meniscus Arrow and vertical or horizontal suture techniques. In
      fresh frozen bovine menisci, initial fixation strength, stiffness and failure
      mode of four different meniscus refixation techniques (Meniscus Arrow, Contour
      Meniscus Arrow, vertical and horizontal 2-0 Ethibond suture techniques) were
      evaluated in a computer-based material-testing machine at a rate of 12.5 mm/s.
      Vertical meniscus sutures showed the highest initial fixation strength, followed
      by the horizontal suture technique and the Contour Arrow. The Meniscus Arrow
      showed inferior pull-out strength. Subjecting the different refixation techniques
      to cyclic testing decreased the fixation strength in all groups. The modified
      Meniscus Anchor (Contour Arrow) provides biomechanical properties that are
      superior (pull-out strength) or similar (stiffness) compared to the first
      biodegradable all-inside implant, the Meniscus Arrow. The pull-out strength of
      the Contour Arrow was comparable to the pull-out strength reported for horizontal
      meniscus sutures in the literature. These biomechanical characteristics of this
      new implant justify clinical use.

PMID- 14689170
TI  - Young adults' relationship transitions and the incidence of mental disorders: a
      three-wave longitudinal study.
AB  - BACKGROUND: Relationship transitions have consistently been found to be
      associated with mental health in young adulthood, but previous studies have not
      demonstrated clearly whether such relationship transitions actually precede the
      development of mental health problems and have focused almost exclusively on
      subclinical levels of problem behavior. METHODS: Longitudinal associations
      between the incidence of mood, anxiety, and substance disorders (DSM-III-R) and
      relationship transitions during young adulthood were examined using data from
      1,581 Dutch young adults aged 18-34, who participated in three waves (1996, 1997,
      and 1999) of a nationwide epidemiological survey. RESULTS: Concurrent 3-year
      longitudinal associations showed that the incidence of mood and substance
      disorders was linked to relationship stability and change (i. e., staying single,
      breaking up/divorcing), but more rigorous, prospective analyses demonstrated that
      only the incidence of substance disorders was associated with previous
      relationship developments. Earlier prevalence of mood disorders increased young
      adults' likelihood of subsequently experiencing a break-up/divorce and lowered
      the likelihood of becoming a parent, but mood disorders were in turn predicted by
      previously experienced relationship difficulties. CONCLUSIONS: Apart from the
      negative consequences of a break-up/divorce, having a relatively unattached
      relationship status (i. e., not stably cohabiting/married, not being a parent)
      may be an important factor in explaining the onset of substance disorders.
      Furthermore, results qualify the notion of de-selection in certain partner roles
      by mood disorders; mood disorders negatively affect individuals' chances of
      staying with one's partner, but are in turn dependent on earlier partner
      relationship quality.

PMID- 14689171
TI  - Sociodemographic and health-related correlates of psychiatric distress in a
      general population.
AB  - BACKGROUND: Measuring factors related to psychiatric distress in public health
      surveys helps to identify groups at risk for developing psychiatric morbidity.
      AIMS: The aim of this study was to determine which socio-demographic and health
      related factors are associated with psychiatric distress in the general
      population. METHOD: Data were from the Catalan Health Interview Survey (CHIS), a
      cross-sectional survey of 15000 members of the general population of Catalonia,
      Spain. The association between scores on the General Health Questionnaire-12 and
      socio-demographic and healthrelated variables was analyzed using logistic
      regression. RESULTS: Several socio-demographic and health-related variables were
      significantly associated with increased psychiatric distress. The factor most
      consistently related to psychiatric distress was the presence of one or more
      chronic physical conditions. The number rather than the type of declared chronic
      conditions was the most important factor,with the odds ratios (OR) for presence
      of psychiatric distress ranging from 1.1 [95% confidence interval (CI) = 1.0-1.4]
      for one declared chronic condition to 5.6 (95% CI = 4.2-7.4) in persons with over
      five chronic conditions. Other significant related variables varied by age and
      gender. CONCLUSIONS: The number of declared chronic physical conditions appears
      to be a relevant correlate of the presence of psychiatric distress, independently
      of other factors, including the type of chronic condition.

PMID- 14689172
TI  - Use of antidepressants in deliberate self-poisoning: psychiatric diagnoses and
      drugs used between 1987 and 1997 in Lund, Sweden.
AB  - OBJECTIVE: Based on the increased prescription of antidepressants, the aim of
      this study was to analyse the changes in self-poisonings with antidepressants
      during the period 1987-1997. METHODS: A total of 909 patients who were admitted
      to hospital after deliberate self-poisoning were investigated regarding
      psychiatric diagnoses and drugs ingested. RESULTS: In the whole group, there was
      no significant change in the rate of antidepressant overdoses between 1987 and
      1990 (20%) and 1995 and 1997 (17 %), but among females with a mood disorder
      overdoses decreased from 43% to 22% (p = 0.01). The proportion of selective
      serotonin reuptake inhibitors (SSRIs) in self-poisonings was significantly lower
      than expected from sales figures. CONCLUSION: The increased antidepressant sales
      have not caused an increased use of antidepressants in self-poisonings. It is,
      therefore, tempting to assume that an increased use of antidepressants for
      appropriate indications causes decreased self-poisoning rates.

PMID- 14689173
TI  - Pathways to care and psychological problems of general practice patients in a
      "gate keeper" and an "open access" health care system: a comparison of Germany
      and the Netherlands.
AB  - BACKGROUND: The comparison of different health care systems is one way to give
      empirical evidence to health care reform and policy. The differences between
      health care systems in which general practitioners serve as gate keepers in
      comparison to systems in which patients are free to contact every physician and
      specialist they like are a question of high interest. METHOD: This study compares
      the Netherlands and Germany, two countries with very similar political, social,
      and health system structures, but different types of access to the health care
      system. While Germany offers unconstrained access to specialist ambulatory care,
      the Netherlands restricts health care utilization by giving primary care a 'gate
      keeper' function not allowing patients direct access to specialist care. Data
      from the WHO international collaborative study on psychological problems in
      general health care (Ustun and Sartorius 1995) were analysed with respect to
      pathways to care, treatment, and health status. In an initial cross-sectional
      assessment, in 3-month and 12-month follow-ups, contacts to physicians or
      hospital admission have also been monitored. RESULTS: There were only marginal
      differences between the Dutch and the German sample in the sociodemographic
      characteristics as well as in the diagnostic status with respect to mental
      disorders. In the Netherlands, 95.5%, and in Germany, 68.8% of the patients
      presented their 'reason for visit' for the first time to any physician at this
      index contact with a general practitioner. During the following 3 months, 24% of
      the Dutch patients, but 60.2% of the German patients, additionally contacted
      other physicians ( P < 0.001). At 12 months, this rate was 62.9% vs. 78.6% ( P <
      0.001). During the 12-month follow-up period, there were 15.7 0/00 hospital
      admissions in Germany vs. 25.4 0/00 in the Netherlands ( P < 0.005) [corrected].
      CONCLUSIONS: Family physicians in a gate keeper system reduce the number of
      contacts to other physicians and the intensity of treatment, while at the same
      time the rate of hospital admissions is increased.

PMID- 14689174
TI  - Mediators of neighbourhood socioeconomic deprivation and quality of life.
AB  - OBJECTIVE: We examined associations between neighbourhood socioeconomic
      deprivation and health-related quality of life, and estimated the mediating
      effects of individual-level lifestyle, housing, and perception of the
      neighbourhood environment. METHODS: Two different data sources were used: 1)
      neighbourhood- level objective socioeconomic indicators, and 2) individual-level
      questionnaires from a community survey (response rate: 48%) to assess quality of
      life, neighbourhood perceptions, housing variables, and lifestyle. Multilevel
      analyses were conducted using both neighbourhood-level and individual-level data.
      RESULTS: Neighbourhood-level socioeconomic deprivation was associated with two
      aspects of individual-level quality of life: mental health and perceived health.
      Individual-level neighbourhood perceptions regarding social cohesion mediated
      these associations. Lifestyle also had mediating effects. CONCLUSION:
      Neighbourhood socioeconomic deprivation variables may impact on the individual
      through cognitive mechanisms that are associated with appraisal of the wider
      social environment.

PMID- 14689175
TI  - Subjective quality of life of recently discharged Nigerian psychiatric patients.
AB  - OBJECTIVES: The objectives of the study were to examine the perceptions of
      recently recovered psychiatric patients on their feeling of well-being, their
      satisfaction with domains of living experience, and the correlates of subjective
      quality of life (QOL). METHOD: Patients (n = 118, aged 18-60) with schizophrenia
      and major affective disorders were assessed with the 26- item WHOQOL instrument,
      2 weeks after discharge. Satisfaction with the items was graded as follows:
      dissatisfaction (< 50% positive appreciation), bare satisfaction (50-65 %),
      moderate (66-74 %), and highest satisfaction (> or = 75 %). In the six domains of
      QOL, patients were categorized as high, average or poor, based on domain mean
      score plus/minus 1 SD. RESULTS: Items of highest satisfaction included overall
      sense of well-being and satisfaction with self; satisfaction with personal
      relationships and ability to work were moderate; while there was dissatisfaction
      with adequacy of money to meet needs, dependence on treatment and sex life. At
      least two-thirds of the subjects were categorized as having average QOL in each
      of the six domains of living experience. There were no significant associations
      between psychiatric diagnosis, socio-demographic characteristics and QOL.
      CONCLUSION: Our data support the impression that effective medical treatment is
      the first step to ensure QOL. Subjective QOL ratings realistically reflect the
      strengths and weaknesses of socio-cultural circumstances and patients' perceived
      personal qualities. High subjective sense of well-being should be a tool in
      public mental health education to dispel the gloom of psychiatric outcome and
      combat stigma.

PMID- 14689176
TI  - Community attitudes toward and knowledge of mental illness in South Africa.
AB  - BACKGROUND: Although recent advances in psychiatry have increased our
      understanding of psychiatric disorders,many people with chronic or severe
      psychiatric disorders may be unaware that effective treatment is available. It is
      possible that ignorance and stigma prevent such persons from seeking appropriate
      help, and that community attitudes and beliefs play a role in determining the
      help-seeking behaviour and successful treatment of the mentally ill.
      Nevertheless, there is little research on the attitudes of lay persons toward
      mental illness within the South African community. OBJECTIVES: The aim of this
      study was to investigate the knowledge and attitudes of the general South African
      public toward mental illness, specifically regarding the causes of illness and
      treatment options. METHOD: The study design employed a questionnaire survey.
      Structured interviews (n = 667) were conducted with members of the general
      public. One of eight vignettes, portraying depression, schizophrenia, panic
      disorder or substance abuse, with subtle or obvious symptoms, was presented to
      each respondent. RESULTS: The main findings were that cases were most often
      conceptualised as stress-related or due to a lack of willpower rather than as
      medical disorders. Treatment advocated was more often to talk the problem over
      than to consult professional medical help. Psychotherapy was the preferred
      treatment option, particularly in vignettes where symptom presentation was
      subtle, and in cases of substance abuse. CONCLUSIONS: These data suggest that
      stigma and misinformation regarding mental illness exist, influencing preferred
      treatment modality and help-seeking behaviour. More work needs to be done to
      educate the public about the psychobiological underpinnings of psychiatric
      disorders and about the value of effective treatments. A better understanding of
      these disorders amongst the public would presumably lessen stigmatisation and
      encourage the use of currently available and effective interventions.

PMID- 14689177
TI  - Patients' understanding and participation in a trial designed to improve the
      management of anti-psychotic medication: a qualitative study.
AB  - BACKGROUND: Combining qualitative methods alongside randomised controlled trials
      in the health field has been advocated but has only been used rarely in mental
      health services research. The aim of this study was to illuminate patients'
      understanding of the nature and purpose and outcomes of a trial designed to
      improve the management of neuroleptic medication. METHODS: Qualitative interviews
      were carried out with a group of patients participating in a trial comparing a
      psycho-educational and therapeutic alliance intervention in managing anti
      psychotic medication. RESULTS: Our findings highlighted aspects of the
      experience, process and outcome of the trial, which remain latent in the
      quantitative assessment. The issue of enlarged selfefficacy emerging when
      patients were involved in communications with professionals in the trial was
      important. Whilst the participants provided positive feedback about their
      involvement in the trial, they struggled to recall the details of the
      intervention to which they had been exposed. Patients did not readily identify
      the content and concepts characterising each condition; rather they prioritised
      the opportunity for communication and contact with the researchers. CONCLUSIONS:
      Qualitative research accompanying trials illuminates and adds to the quantitative
      outcomes. The key to interpreting participants' accounts of the process and
      outcomes of this trial suggests the need to give greater emphasis to
      participants' past and current experience of service contact.

PMID- 14689178
TI  - Considering comorbidity in social phobia.
AB  - BACKGROUND: Considering comorbidity in social phobia contributes to our
      understanding of causal pathways and improved classifications for psychiatric
      disorders. Comorbidity also has important clinical implications. While a number
      of studies have investigated comorbidity in social phobia, only one other study
      has used the Composite International Diagnostic Interview (CIDI) and considered
      comorbidity in subtypes of social phobia. This study evaluated lifetime social
      phobia comorbidity with other common mental disorders as well as comorbidity in
      subtypes of social phobia. We also considered whether social fears, reported by
      respondents with social phobia, had an earlier or later age of onset than other
      disorders. METHODS: Data came from the Mental Health Supplement to the Ontario
      Health Survey, a survey of 8,116 Canadian respondents, ages 15-64. Psychiatric
      diagnoses were determined using the CIDI. This instrument is considered more
      sensitive than earlier instruments for diagnosing social phobia. RESULTS: Fifty
      two percent of respondents with lifetime social phobia reported at least one
      other lifetime mental disorder and 27% reported three or more lifetime mental
      disorders. Social phobia, in this sample, is strongly comorbid with anxiety and
      affective disorders, and moderately comorbid with substance abuse disorders. When
      two social phobia subgroups were considered, the largest odds ratios were found
      among the not-exclusively-speaking social phobia group. This subgroup would
      include most of the respondents with a generalized form of social phobia. Age of
      onset of social fears, in respondents with social phobia, preceded age of onset
      of the comorbid disorder in 32% of cases with comorbid anxiety disorder, 71% of
      cases with comorbid affective disorder and 80% of cases with comorbid substance
      dependence/abuse disorder. CONCLUSIONS: Comorbidity and relative age of onset
      among respondents with social phobia in this study are generally consistent with
      previous epidemiologic studies. Clinicians should be vigilant for comorbidity in
      social phobia and should select treatments that target the full range of comorbid
      disorders. Early intervention or prevention of social fears or social phobia has
      the potential to reduce the risk of comorbid disorders.

PMID- 14689184
TI  - Identification of incompatibility alleles in the tetraploid species sour cherry.
AB  - The incompatibility genetics of sour cherry ( Prunus cerasus), an allotetraploid
      species thought to be derived from sweet cherry (diploid) and ground cherry
      (tetraploid), were investigated by test crossing and by analysis of stylar
      ribonucleases which are known to be the products of incompatibility alleles in
      sweet cherry. Stylar extracts of 36 accessions of sour cherry were separated
      electrophoretically and stained for ribonuclease activity. The zymograms of most
      accessions showed three bands, some two or four. Of the ten bands seen, six co
      migrated with bands that in sweet cherry are attributed to the incompatibility
      alleles S(1), S(3), S(4), S(6, ) S(9) and S(13). 'Cacanski Rubin', 'Erdi Botermo
      B', 'Koros' and 'Ujfehertoi Furtos', which showed bands apparently corresponding
      to S(1) and S(4), were test pollinated with the sweet cherry 'Merton Late' ( S(1)
      S(4)). Monitoring pollen tube growth, and, in one case, fruit set, showed that
      these crosses were incompatible and that the four sour cherries indeed have the
      alleles S(1) and S(4). Likewise, test pollination of 'Marasca Piemonte', 'Marasca
      Savena' and 'Morello, Dutch' with 'Noble' ( S(6) S(13)) showed that these three
      sour cherries have the alleles S(6) and S(13). S(13) was very frequent in sour
      cherry cultivars, but is rare in sweet cherry cultivars, whereas with S(3) the
      situation is reversed. It was suggested that the other four bands are derived
      from ground cherry and one of these, provisionally attributed to S(B), occurred
      frequently in a small set of ground cherry accessions surveyed. Analysing some
      progenies from sour by sweet crosses by S allele-specific PCR and monitoring the
      success of some sweet by sour crosses were informative. They indicated mostly
      disomic inheritance, with sweet cherry S alleles belonging to one locus and,
      presumably, the ground cherry alleles to the other, and helped clarify the
      genomic arrangement of the alleles and the interactions in heteroallelic pollen.

PMID- 14689186
TI  - Advantage of single-trial models for response to selection in wheat breeding
      multi-environment trials.
AB  - An investigation was conducted to evaluate the impact of experimental designs and
      spatial analyses (single-trial models) of the response to selection for grain
      yield in the northern grains region of Australia (Queensland and northern New
      South Wales). Two sets of multi-environment experiments were considered. One set,
      based on 33 trials conducted from 1994 to 1996, was used to represent the testing
      system of the wheat breeding program and is referred to as the multi-environment
      trial (MET). The second set, based on 47 trials conducted from 1986 to 1993,
      sampled a more diverse set of years and management regimes and was used to
      represent the target population of environments (TPE). There were 18 genotypes in
      common between the MET and TPE sets of trials. From indirect selection theory,
      the phenotypic correlation coefficient between the MET and TPE single-trial
      adjusted genotype means [ r(p(MT))] was used to determine the effect of the
      single-trial model on the expected indirect response to selection for grain yield
      in the TPE based on selection in the MET. Five single-trial models were
      considered: randomised complete block (RCB), incomplete block (IB), spatial
      analysis (SS), spatial analysis with a measurement error (SSM) and a combination
      of spatial analysis and experimental design information to identify the preferred
      (PF) model. Bootstrap-resampling methodology was used to construct multiple MET
      data sets, ranging in size from 2 to 20 environments per MET sample. The size and
      environmental composition of the MET and the single-trial model influenced the
      r(p(MT)). On average, the PF model resulted in a higher r(p(MT)) than the IB, SS
      and SSM models, which were in turn superior to the RCB model for MET sizes based
      on fewer than ten environments. For METs based on ten or more environments, the
      r(p(MT)) was similar for all single-trial models.

PMID- 14689183
TI  - Insulin secretion profiles are modified by overexpression of glutamate
      dehydrogenase in pancreatic islets.
AB  - AIMS/HYPOTHESIS: Glutamate dehydrogenase (GDH) is a mitochondrial enzyme playing
      a key role in the control of insulin secretion. However, it is not known whether
      GDH expression levels in beta cells are rate-limiting for the secretory response
      to glucose. GDH also controls glutamine and glutamate oxidative metabolism, which
      is only weak in islets if GDH is not allosterically activated by L-leucine or (+/
      )-2-aminobicyclo-[2,2,1]heptane-2-carboxylic acid (BCH). METHODS: We constructed
      an adenovirus encoding for GDH to overexpress the enzyme in the beta-cell line
      INS-1E, as well as in isolated rat and mouse pancreatic islets. The secretory
      responses to glucose and glutamine were studied in static and perifusion
      experiments. Amino acid concentrations and metabolic parameters were measured in
      parallel. RESULTS: GDH overexpression in rat islets did not change insulin
      release at basal or intermediate glucose (2.8 and 8.3 mmol/l respectively), but
      potentiated the secretory response at high glucose concentrations (16.7 mmol/l)
      compared to controls (+35%). Control islets exposed to 5 mmol/l glutamine at
      basal glucose did not increase insulin release, unless BCH was added with a
      resulting 2.5-fold response. In islets overexpressing GDH glutamine alone
      stimulated insulin secretion (2.7-fold), which was potentiated 2.2-fold by adding
      BCH. The secretory responses evoked by glutamine under these conditions
      correlated with enhanced cellular metabolism. CONCLUSIONS/INTERPRETATION: GDH
      could be rate-limiting in glucose-induced insulin secretion, as GDH
      overexpression enhanced secretory responses. Moreover, GDH overexpression made
      islets responsive to glutamine, indicating that under physiological conditions
      this enzyme acts as a gatekeeper to prevent amino acids from being inappropriate
      efficient secretagogues.

PMID- 14689187
TI  - Molecular comparison of waxy null alleles in common wheat and identification of a
      unique null allele.
AB  - PCR selection markers for the identification of null waxy alleles were used to
      screen for waxy mutations in 168 common wheat cultivars. In all cultivars where
      the Wx-B1 protein was absent, the Wx-B1 allele was identical to the previously
      identified mutation carried by Kanto 107. Although most cultivars missing the Wx
      A1 protein also carried the same Wx-A1 mutation as found in Kanto 107, all of the
      Turkey Wx-A1 mutants produced a different PCR fragment, implying the presence of
      a different mutation. Sequencing of this fragment indicated the mutation, which
      consisted of a 173-bp insertion in an exon, was in a different location than the
      previously identified Wx-A1 mutation. An 8-bp duplication of the Wx-A1 sequence
      flanked each end of the insertion, and an element with reverse complementary
      sequences was present at both ends of the insertion. These structures correspond
      with the features of class II transposable elements. Hence, the Turkey null Wx-A1
      mutation was likely caused by the movement of a transposon, and this spontaneous
      mutation appears to be present in a limited geographical area.

PMID- 14689189
TI  - Molecular mapping of Fusarium oxysporum f. sp. ciceris race 3 resistance gene in
      chickpea.
AB  - Sequence-tagged microsatellite site (STMS) and sequence-tagged site (STS) markers
      linked closely to Fusarium oxysporum f. sp. ciceris race 3 resistance gene in
      chickpea were identified, and linkage between three wilt resistance genes was
      elucidated. The resistance to race 3 in chickpea germplasm accession WR-315 was
      inherited as a single gene, designated foc-3, in 100 F(7) recombinant inbred
      lines derived from the cross of WR-315 (resistant) x C-104 (susceptible). The foc
      3 gene was mapped 0.6 cM from STMS markers TA96 and TA27 and STS marker CS27A.
      Another STMS marker, TA194, at 14.3 cM, flanked the gene on the other side.
      Linkage between foc-3 and two other chickpea wilt resistance genes, foc-1 (syn.
      h(1)) and foc-4, was established. foc-3 was mapped 9.8 cM from foc-1 and 8.7 cM
      from foc-4, whereas foc-1 and foc-4 are closely linked at 1.1 cM. The
      identification of closely linked markers to resistance genes will facilitate
      marker-assisted selection for introgression of the race 3 resistance gene to
      susceptible chickpea lines.

PMID- 14689188
TI  - High-resolution genetic mapping of the leaf stripe resistance gene Rdg2a in
      barley.
AB  - The dominant gene Rdg2a of barley conferring resistance to the hemi-biotrophic
      seed-borne pathogen Pyrenophora graminea is located in the distal region of
      chromosome arm 1 (7H)S. As the first step towards isolating the gene, a high
      resolution genetic map of the region was constructed using an F(2) population of
      1,400 plants (Thibaut Rdg2axMirco). The map included six classes of resistance
      gene analogues (RGAs) tightly associated with Rdg2a. Rdg2a was delimited to a
      genetic interval of 0.14 cM between the RGAs ssCH4 and MWG851. Additional markers
      were generated using the sequence from the corresponding region on rice
      chromosome 6, allowing delimitation of the Rdg2a syntenic interval in rice to a
      115 kbp stretch of sequence. Analysis of the rice sequence failed to reveal any
      genes with similarity to characterized resistance genes. Therefore, either the
      rice-barley synteny is disrupted in this region, or Rdg2a encodes a novel type of
      resistance protein.

PMID- 14689191
TI  - [Therapy and secondary prevention of venous thromboembolism with vitamin K
      antagonists].
AB  - Oral anticoagulation with vitamin-K-antagonists is very effective in secondary
      prevention of venous thromboembolism. In Germany, most commonly Phenprocoumon is
      used, while most of the evidence-based data are available for Warfarin. The
      initial treatment of acute venous thromboembolism requires immediate
      anticoagulation with heparin and a subsequent overlapping treatment with oral
      anticoagulants. During this phase, anticoagulation may be unstable with increased
      risk for bleeding. An INR target range between 2 and 3 provides effective
      protection with minimal risk for major bleeding. The individual risk for bleeding
      may be estimated by a clinical score. Six months of oral anticoagulation is the
      standard duration for a first episode of venous thromboembolism, while
      recurrencies are treated for at least one to two years. The duration may be
      tailored to the individual patient according to underlying risk factors for
      recurrencies and for bleeding. Because of a plethora of practical problems and
      the narrow therapeutic window, there is a need for new antithrombotic agents.
      These may allow a longer duration of secondary prevention with improved
      protection against recurrencies without sacrificing safety.

PMID- 14689190
TI  - [Liver replacement therapy. Reliable indications in acute liver failure].
AB  - Extracorporeal liver support devices aim at improving the therapeutical options
      for liver failure. Numerous artificial and bioartificial devices have been tested
      to reduce the high mortality of this dynamic disease. In particular, the
      detoxification function of the liver should be upheld, by means of a number of
      different procedures, either until liver function is restored or until
      transplantation. Both purely artificial, machine-based procedures including
      different forms of dialysis and hemoadsorption as well as bioartificial
      procedures based on hepatocytes are being tested, as are different types of
      extracorporeal liver perfusion. This paper provides an overview of the different
      methods and devices and their clinical evidence in order to give a recommendation
      for the handling of the expensive devices. There is no current indication for the
      application of liver support devices outside of clinical studies at specialised
      centres.

PMID- 14689192
TI  - [Hormone therapy in menopause. A current update].
AB  - While the use of hormone replacement therapy (HRT) for prophylactic indications
      such as cardiovascular disease, osteoporosis, and Alzheimer's disease was
      increasingly propagated during the 1990s, recent studies have reported no risk
      reduction for women after myocardial infarction (HERS) or women from a mixed
      population with an average age of 63 years (Women's Health Initiative [WHI]
      Study). The results of the latter study even suggest an increased risk for
      cardiovascular events and breast cancer with previous or ongoing combined oral
      estrogen plus progestin. A final risk-benefit assessment for estrogen monotherapy
      will only be possible after the ongoing part of the WHI Study has been evaluated,
      expected in 2005. As effects, side effects, and contraindications for HRT in
      postmenopausal women are better known, the need for individualized risk
      assessment and the definition of therapeutic goals increases. Since the WHI Study
      did not address the risk-benefit ratio for women with perimenopausal complaints
      or osteoporosis or with lower dose hormone preparations commonly used in Germany,
      there is an urgent need to answer these open questions with large confirmative
      studies.

PMID- 14689193
TI  - [Therapy of acute pancreatitis].
AB  - Despite our increasing knowledge in the pathophysiology of acute pancreatitis
      therapeutic strategies based on this knowledge, such as inhibition of proteases,
      are not convincing. It is most likely that these strategies are initiated to late
      after the onset of pancreatitis. It is of utmost importance to clarify the
      severity of the disease for planning interdisciplinary approaches: therapy of
      pain, enteral nutrition via a jejunal tube, as well as treatment of
      extrapancreatic complications, such as respiratory insufficiency, coagulopathy,
      and renal insufficiency. A key role plays the exact balance of potential high
      fluid losses. Prophylactic application of antibiotics such as imipenem in cases
      of necrotizing pancreatitis to prevent infection is widely used. Infected
      necroses are an indication for surgery. In biliary pancreatitis one has to remove
      impacted bile duct stones via ERCP and papillotomy followed by elective
      cholecystectomy.

PMID- 14689195
TI  - [Pharmacogenomics. What is relevant for the internal medicine specialist?].
AB  - Epidemiological observational studies have shown existing interindividual and
      interethnical differences in drug metabolism. This results in a great variety of
      effects and side effects of drugs. One reason for these variabilities are genetic
      polymorphisms which occur on the basis of single-nucleotide exchanges or
      insertional and deletional mutations. Such mutations may involve transport
      proteins or metabolizing enzymes of phase I and phase II reactions, as cytochrome
      P450, glucuronidases and enzymes which metabolize cytostatics. The differences in
      pharmacokinetics and pharmacodynamics have an impact on therapeutical outcome.
      Dosage adjustments should be undertaken before the initiation of therapy in
      reflection of modern genotyping. This is particularly important in oncology to
      avoid life-threatening adverse drug reactions. Examples of cardiovascular and
      neurological diseases are presented to demonstrate the impact of genetic
      polymorphisms on the incidence and prevalence of diseases as well as the
      responses to medications like beta blockers, ACE inhibitors and psychotropic
      drugs. Finally, additional factors are summarized, which may contribute to the
      large diversity of drug reactions.

PMID- 14689194
TI  - [Therapy of chronic pancreatitis].
AB  - Treatment of chronic pancreatitis is dependend on the stage of the disease and
      its complications. Pain therapy should be based on the knowledge of various
      causes of pain. In therapy of complications such as bile duct or pancreatic duct
      strictures interventional endoscopy is usually the first choice followed by
      surgery. Exocrine insufficiency is treated by porcine pancreatic extracts,
      endocrine insufficiency by insulin. One has to apply various imaging procedures
      such as sonography, MRCP, ERCP, endosonography, CT for exact diagnosis of
      complications and planning various therapeutic strategies. Pseudocysts may be
      drained via the transgastric, transduodenal, transpapillary or transcutaneous
      route. Distal prepapillary stenosis of the main pancreatic duct and bile duct
      stenoses can be drained by stents. Pancreatic duct stones can be desintegrated by
      shock waves and removed by endoscopy. Early diagnosis of pancreatic carcinoma as
      a potential complication of long standing inflammation of the pancreas remains an
      unsolved problem.

PMID- 14689196
TI  - [Progress in therapy of infection].

PMID- 14689197
TI  - [Therapy of primary systemic vasculitis].
AB  - The treatment of systemic vasculitides has changed during the past ten years from
      a uniform immunosuppressive regimen consisting of cyclophosphamide and
      prednisolone to a stage- and activity-adapted, more differentiated
      immunosuppressive and immunomodulating therapy. Due to the low incidence of these
      diseases, the assessment of these regimens by prospective, randomized, controlled
      trials has only been enabled through multicenter cooperation. In primary systemic
      vasculitides of small- or medium-sized vessels induction of remission therapy
      comprises methotrexate in early generalized disease without significant renal
      insufficiency, cyclophosphamide in full-blown generalized disease and additional
      plasma exchanges in cases of rapidly progressive glomerulonephritis if oliguric,
      each in conjunction with oral prednisolone. After achievement of remission
      patients are switched to a less potent maintenance of remission therapy with
      better long-term tolerability, such as azathioprine. Glucocorticoids are the
      mainstay for large vessel vasculitides, supplemented by azathioprine or
      methotrexate in cases of critical organ perfusion or demand for high steroid
      doses. Therapy for secondary vasculitides relies essentially on the treatment of
      the underlying disease, which means virus elimination in cases of hepatitis B or
      C associated vasculitides. Immunosuppression in these diseases is reserved for
      organ- or life-threatening manifestations only.

PMID- 14689199
TI  - ["Peculiar infection" with fever, splenomegaly and acute kidney failure in a 24
      year-old forestry student].
AB  - When confronted by the combination of initial high fever associated with intense
      malaise, splenomegaly, elevated levels of transaminases, and acute renal failure,
      consideration must be given to the differential diagnosis of leptospirosis even
      in Germany. As a rule, the diagnosis is confirmed by serological testing based on
      the titer curve. Renal involvement is frequent, but usually has a good prognosis,
      especially if jaundice has not developed. Treatment with doxycycline or
      penicillin can shorten the disease course and exudation, possibly also the
      nephritis, or hinder it.

PMID- 14689198
TI  - [Therapy of severe fungal infections].
AB  - Severe fungal infections increase in numbers in the Western world. This is due to
      more intensive therapies against cancers leading to severe and prolonged
      immunosuppression. For many years treatment of severe fungal infections had to be
      done solely with amphothericin B desoxycholate and 5-fluorocytosine. With the
      advent of triazoles such as fluconazole, lipid formulations of amphotericin B and
      the development of echinocandines such as caspofungin also severe candidiasis and
      invasive aspergillosis has become treatable. In particular, caspofungin for
      invasive candidiasis and voriconazole for invasive aspergillosis seem at least
      equivalent to amphotericin B. A clear advantage is the advent of lipid
      formulations of amphotericin B. This regards especially side effects which are
      reduced with these newer formulations, i.e. nephrotoxicity. Due to the fact that
      prospective trials are difficult to conduct because patient populations may vary
      considerably (especially the underlying disease) many comparisons were not yet
      performed. Nevertheless, promising results indicate that certain combinations of
      antifungals may enhance prognosis of refractory fungal infections with a so far
      very serious prognosis.

PMID- 14689200
TI  - [62-year-old patient with progressive dyspnea and positional left-sided thoracic
      pain].
AB  - A 62-year-old male patient presented with left-sided chest pain experienced in a
      lying position and progressive dyspnea. He had a history of thyroid carcinoma
      treated 22 years ago and a nodular shadow in the left lung first identified 9
      years ago. He refused any further diagnostic and therapeutic measures for the
      nodular shadow as he had been free of symptoms. The clinical findings at
      presentation included labial and acral cyanosis. Breathing sounds over the lower
      left lung were diminished. A chest X-ray revealed a 9 x 8-cm cloudiness lateral
      to the left border of the heart, which was confirmed in a contrast thoracic CT
      evidencing a smooth surface and a wall absorbing contrast medium. Staging
      diagnostics indicated no further tumor manifestations. Needle biopsy showed
      fibrous tissue. Thoracotomy with tumor extirpation exhibited a solitary fibrous
      tumor of the pleura. Solitary fibrous tumor of the pleura is a rare cause for a
      nodular shadow of the lung. Clinical findings are rather nonspecific. Complete
      resection is the therapy of choice. Resection of functional lung tissue has to be
      avoided because the tumor often is pediculated.

PMID- 14689201
TI  - [Pharmacotherapy of patients with dementia].
AB  - Dementing illnesses present among the most frequent and most consequential
      psychiatric disorders in old age. They thus constitute a particular challenge for
      science politics and society as a whole. Knowledge about multifactorial
      etiological and pathological factors is still rather limited. By way of
      stratified diagnostic procedures various dementia disorders can be differentiated
      rather reliably. Anti-dementia drugs can enhance cognitive performance and
      temporarily slow down the progress of the most frequently occurring dementias
      (Alzheimer-dementia, vascular dementia). In the treatment of behavioral symptoms
      in dementia newly developed psychopharmological agents are of particular
      relevance. They constitute an important element of a multi-modal therapeutic
      strategy.

PMID- 14689202
TI  - [Highly active antiretroviral therapy of HIV patients. ART Cohort Collaboration].

PMID- 14689203
TI  - [Nephrology as scientific focus. Report on the World Congress of Nephrology, 8-12
      June 2003].

PMID- 14689204
TI  - Active stress kinase p38 enhances and perpetuates abnormal tau phosphorylation
      and deposition in Pick's disease.
AB  - Abnormal tau hyperphosphorylation and deposition in Pick bodies is a major
      abnormality in Pick's disease (PiD). This is associated with increased expression
      of the stress-activated protein kinase, p38 kinase, which has the capacity to
      phosphorylate tau in vitro. The present study has shown increased expression of
      phosphorylated p38 (p38-P), which does not cross-react with phospho-tau, in
      sarcosyl-insoluble fractions enriched in abnormal filaments, and
      hyperphosphorylated tau in the brain of two PiD cases obtained and processed with
      very short (less than 2 h) post-mortem delay. Immunohistochemical studies have
      shown p38-P co-localization in 90% of neurons with Pick bodies, whereas no
      positive cells are encountered in control brains processed in parallel. Moreover,
      p38-immunoprecipitated from sarcosyl-insoluble fractions in PiD brains is
      functionally active as it has the capacity to phosphorylate its specific
      substrate ATF-2. Combined biochemical, immunohistochemical and functional studies
      indicate that active p38 kinase is expressed in a very high percentage of Pick
      bodies, thus suggesting a critical role of this kinase in enhancing and
      perpetuating tau hyperphosphorylation in PiD.

PMID- 14689205
TI  - Phagocytosis of Escherichia coli by amoeboid microglial cells in the developing
      brain.
AB  - Amoeboid microglial cells (AMC) in the corpus callosum of 1-day-old rats
      receiving a single intracerebral injection of Escherichia coli ( E. Coli) were
      examined at various time intervals following the injection. A large number of E.
      coli were internalized by the AMC at 1-3 h after the injection. However, no E.
      coli were identifiable at 1 day after the injection, but large phagosomes were
      observed in the cytoplasm of AMC. With time, the phagosomes in the AMC were
      reduced so that by 7 days the cells appeared comparable to the controls.
      Apoptotic or necrotic AMC were not encountered during the study period. This is
      consistent with the results of cell counts, which showed no significant change in
      the AMC population following E. coli injection compared with controls. The
      present results suggest that AMC are capable of removing live bacteria from their
      vicinity. Up-regulation of complement type 3 receptors and induction of major
      histocompatibility complex class II antigens were observed in the AMC at days 1-3
      and 7 following E. coli administration. This may be related to their involvement
      in mediating endocytosis and their possible role in antigen presentation.

PMID- 14689206
TI  - 50-Hz magnetic field exposure influences DNA repair and mitochondrial DNA
      synthesis of distinct cell types in brain and kidney of adult mice.
AB  - Despite several recent investigations, the impact of whole-body magnetic field
      exposure on cell-type-specific alterations due to DNA damage and DNA repair
      remains unclear. In this pilot study adult mice were exposed to 50-Hz magnetic
      field (mean value 1.5 mT) for 8 weeks or left unexposed. Five minutes after
      ending exposure, the mice received [(3)H]thymidine and were killed 2 h later.
      Autoradiographs were prepared from paraffin sections of brains and kidneys for
      measuring unscheduled DNA synthesis and mitochondrial DNA synthesis, or in situ
      nick translation with DNA polymerase-I and [(3)H]dTTP. A significant (P<0.05)
      increase in both unscheduled DNA synthesis and in situ nick translation was only
      found for epithelial cells of the choroid plexus. Thus, these two independent
      methods indicate that nuclear DNA damage is produced by long-lasting and strong
      magnetic field exposure. The fact that only plexus epithelial cells were affected
      might point to possible effects of magnetic fields on iron transport across the
      blood-cerebrospinal fluid barrier, but the mechanisms are currently not
      understood. Mitochondrial DNA synthesis was exclusively increased in renal
      epithelial cells of distal convoluted tubules and collecting ducts, i.e., cells
      with a very high content of mitochondria, possibly indicating increased metabolic
      activity of these cells.

PMID- 14689207
TI  - A case of primary extramedullary plasmacytoma of the colon.

PMID- 14689208
TI  - Pseudo-colonic carcinoma caused by abdominal actinomycosis: report of two cases.
AB  - BACKGROUND: Abdominal actinomycosis is an infrequent chronic, suppurative
      infection caused by the aerobic gram-positive bands Actinomyces israelii. PATIENT
      PRESENTATION: We report two cases of abdominal actinomycosis, simulating colon
      cancer. Before operation, both patients presented with abdominal pain and a
      palpable mass. Abdominal computed tomography (CT) revealed an infiltrating
      irregular mass in the cecum and transverse colon, respectively. Surgical
      intervention was then performed under the impression of colonic malignancy.
      CONCLUSION: Postoperatively, pathologic examination confirmed the diagnosis of
      abdominal actinomycosis in which the characteristic finding of sulfur granules in
      the resected specimen was demonstrated. After surgery, the patients continued
      antibiotic treatment with ampicillin for 2 months at our OPD and had no signs of
      recurrence 1 year after surgery.

PMID- 14689209
TI  - Seven cases of neonatal appendicitis with a review of the English language
      literature of the last century.
AB  - Neonatal appendicitis (NA) is a very rare surgical condition. The aim of this
      study is to once again draw attention to this subject by collecting our cases
      with NA and cases of NA reported separately in English-language literature over
      the period from 1901 to 2000. We performed a retrospective chart review of
      patients admitted to our hospital, with the clinical diagnosis of NA from 1990 to
      2000. A survey of the English-language literature together with our own 7 cases
      revealed a total of 141 cases of NA during the period of 1901-2000. 128 cases had
      sufficient information for analysis. The patients are grouped and discussed
      according to these 3 time- periods: 1901-1975, 1976-1984 and 1985-2000. The
      incidence, etiology, and presenting signs and symptoms of appendicitis in
      newborns are discussed. Despite the similar perforation rates in the 3 time-
      periods (73%, 70%, 82%), mortality rate in NA has decreased from 78% in the 1901
      1975 period, to 33% in the 1976-1984 period, and to 28% in the 1985-2000 period.
      A newborn baby presenting with continuous vomiting, refusal to feed, and, showing
      signs of pain through irritability, restlessness, sleep disturbance, and a
      distended abdomen; one should strongly suspect an abdominal disorder, perhaps
      appendicitis.

PMID- 14689210
TI  - Plasticity of the enteric nervous system in patients with intestinal neuronal
      dysplasia associated with Hirschsprung's disease: a report of three patients.
AB  - Intestinal neuronal dysplasia is a controversial form of dysganglionosis that has
      been described both as an isolated disorder and in association with
      Hirschsprung's disease. It has been blamed for the bad outcome of bowel function
      in patients operated on for Hirschsprung's disease. According to various authors,
      intestinal neuronal dysplasia could be a primary disorder or secondary to other
      diseases of the bowel. The aim of this study was to assess the plasticity of the
      enteric nervous system in patients with Hirschsprung's disease-associated
      intestinal neuronal dysplasia and its ability to evolve spontaneously to normal
      innervation patterns. Since we prospectively introduced the assessment of the
      enteric nervous system of the ganglionated bowel in patients operated on for
      Hirschsprung's disease, 31 patients have been operated on for Hirschsprung's
      disease in our institution between 1995 and 2002. Among these patients, nine
      suffered postoperatively from severe constipation and five from bouts of
      entocolitis. IND was found in eight of them. We studied the evolution of the
      innervation in three of these patients by repeated serial full-thickness biopsies
      of the colon. All three patients underwent a colostomy before or after the pull
      through procedure. Histopathological assessment of the enteric nervous system was
      made with conventional acetylcholinesterase histochemistry, rapid
      acetylcholinesterase histochemistry and immunohistochemistry for the Protein Gene
      Product 9.5 and the antigen CD56. This evolution was compared with the clinical
      outcome of bowel function. In our three patients with Hirschsprung's disease
      associated intestinal neuronal dysplasia, this form of dysganglionosis evolved to
      normal innervation patterns within a period ranging from 9 to 18 months. This
      evolution was accompanied by an improvement of bowel function in all. We conclude
      that Hirschsprung's disease-associated intestinal neuronal dysplasia can evolve
      to a normal innervation, at least under certain circumstances such as a
      colostomy. Specific histopathological techniques are required to assess
      accurately the enteric nervous system.

PMID- 14689211
TI  - Neuroblastoma detected by mass screening: the Tumor Board's role in its
      treatment.
AB  - Japan has a nationwide mass-screening program for neuroblastoma in 6-month-old
      infants. Neuroblastoma can regress spontaneously, and some institutions observe
      selected cases. We evaluated the management of screened neuroblastoma at our
      hospital since 1997 when an observation program was introduced. Criteria for the
      observation program were stage-I, stage-II, or stage-IVs tumors, urinary
      vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels <40 microg/mg
      creatinine, tumor <5 cm in diameter, no invasion to the intraspinal canal or
      great vessels, and parental consent to participate. Patients who did not meet
      observation criteria underwent surgery or mild chemotherapy according to the
      location of the tumor. If patients met observation criteria after chemotherapy,
      surgical intervention was no longer performed. Thirty-six patients attended our
      hospital for screened neuroblastoma from 1997 to 2002. Thirty-three patients who
      were managed at our hospital participated in this study. Ten subjects met
      observation criteria. Tumors regressed in 7 patients (mean follow-up period 36.3
      months) with corresponding decreases in VMA and HVA levels (group A). Three
      underwent surgery (group B) because of increasing VMA and HVA levels, increase in
      tumor size, or guardian's request. Twenty-three subjects did not meet observation
      criteria. Four patients underwent primary surgery (group C), and 19 patients had
      chemotherapy initially. Fourteen patients met observation criteria after
      chemotherapy and two are still having chemotherapy (group D). Three patients
      required surgery due to insufficient regression of their tumors (group E).
      Fourteen subjects in group D had marked decreases in VMA and HVA levels and tumor
      size (mean follow-up period 29.1 months), and tumors were not detected using
      imaging techniques in 8 patients. Histological examination of all resected
      specimens during the study period showed favorable histology and no N-myc
      amplification. There was no evidence of unfavorable prognosis in any of the 33
      subjects, although 1 patient who underwent primary surgery had a vanishing kidney
      1 year later and 1 patient had multiple bony metastases after complete resection
      of tumor, which was treated by chemotherapy. Until the real significance of mass
      screening for neuroblastoma as a public health measure is confirmed, observation
      with careful follow-up should be adopted more extensively because it has a
      favorable outcome in many cases, and is associated with minimal therapeutic
      complications.

PMID- 14689212
TI  - Fetal surgery for repair of myelomeningocele allows normal development of anal
      sphincter muscles in sheep.
AB  - One major problem for patients with myelomeningocele (MMC) is fecal incontinence.
      To prevent this problem, fetal surgery for repair of MMC has been recently
      undertaken. The strategy behind this surgery is to allow normal development of
      anal sphincter muscles. The purpose of this study was to determine whether fetal
      surgery for repair of MMC allows normal development of anal sphincter muscles.
      Myelomeningocele was surgically created in fetal sheep at 75 days of gestation.
      At 100 days of gestation, fetal surgery for repair of the MMC lesion was
      performed. Three repair methods were used: standard neurosurgical repair (4 fetal
      sheep), covering the MMC lesion with Alloderm (2 fetal sheep), and covering the
      MMC lesion with Gore-Tex (2 fetal sheep). After the sheep were delivered (140
      days of gestation), external and internal anal sphincter muscles were analyzed
      histopathologically. In control fetal sheep (not repaired) anal sphincter muscles
      did not develop normally. In contrast, in fetal sheep that underwent repair of
      the MMC, the external and internal anal sphincter muscles developed normally.
      Histopathologically, in the external sphincter muscles, muscle fibers were dense.
      In the internal sphincter muscles, endomysial spaces were small, myofibrils were
      numerous, and fascicular units were larger than those in unrepaired fetal sheep.
      There was no difference in muscle development for the repair methods. Fetal
      surgery for repair of MMC allows normal development of anal sphincter muscles.

PMID- 14689213
TI  - Efficacy of real-time monitoring to determine motility in porcine small
      intestinal transplantation.
AB  - Orthotropic small intestinal transplantation (SIT) was performed in outbred 20
      pigs. The interdigestive motor patterns were evaluated using strain gage (SG)
      force transducers. Seven pigs without SIT were treated as control (C) group.
      Based on the obtained data, the group, which could be detected the migrating
      motor complex (MMC) in the graft and alive with adequate oral feeding, was
      regarded as functional graft (FG) group, whereas the group which had available
      data recorded within 10 days before the death due to rejection was regarded as
      rejection (R) group. The MMC was analyzed using following parameters: duration;
      amplitude; and interval. In group FG, all parameters were almost same as group C,
      thus suggesting that the allograft in group FG had a normal motor function. In
      contrast, all parameters in group R were significantly lower than those in group
      FG, suggesting that the motility in group R was impaired. The SG method could
      monitor the real-time motility and was efficient for detecting the rejection of
      SIT.

PMID- 14689214
TI  - Effect of a nucleoside/nucleotide-free diet in rat allogenic small intestinal
      transplantation.
AB  - The aim of this study is to estimate the effect of nucleoside (NS) and nucleotide
      (NT) on the recipient and graft immune response after rat allogenic small
      intestinal transplantation. Seven-week-old Lewis rats were randomly assigned to
      two groups, including the NS/NT free group ( n=6) and the NS/NT supplemented
      group ( n=6), according to the diet received. The recipient Lewis rats were each
      given diet for 12 days, and then, on the nineteenth day of gestation, a 2 cm
      jejunum from the donor fetal Fischer rat was transplanted into the abdominal wall
      of the recipient rats using a non-vascular anastomotic technique. The recipient
      rats were killed on day 2 after transplantation, and then the recipient plasma
      interleukin-2 (IL-2) level was measured. In addition, the histological findings
      of the graft were analyzed. The IL-2 level of the NS/NT free group was
      significantly lower than that of the NS/NT supplemented group. In order to
      determine the grade of rejection, the morphological findings were blindly graded
      on a scale of 0-4. The mean grade of the NS/NT free group was also significantly
      lower than that of the NS/NT supplemented group. The NS/NT free diet is therefore
      considered to have an immunosuppressive effect on rat allogenic small intestinal
      transplantation based on the recipient plasma IL-2 levels and the histological
      findings of the grafts.

PMID- 14689215
TI  - Magnetic resonance cholangiopancreatography on postoperative work-up in children
      with choledochal cysts.
AB  - This study aimed to assess the clinical usefulness of magnetic resonance
      cholangiopancreatography (MRCP) as a postoperative diagnostic tool in children
      with choledochal cysts. Magnetic resonance cholangiopancreatography was performed
      postoperatively in 19 patients and image quality was compared with that obtained
      by intravenous cholangiography spiral computed tomography (IVC-SCT). While the
      detectability by MRCP was inferior to that by IVC-SCT, MRCP highly (84.2%)
      depicted the anastomotic site together with the reconstructed bowel and
      intrahepatic bile ducts. Magnetic resonance cholangiopancreatography also clearly
      delineated the postoperative condition of pancreaticobiliary maljunction (PBM),
      residual distal common bile duct, common channel, and pancreatic duct. Since MRCP
      is noninvasive and requires neither radiation exposure nor a contrast agent, and
      is useful for detecting both anastomosis and pancreatico-biliary ducts around
      PBM, MRCP might be superior to IVC-SCT as an imaging technique for outpatient
      clinics performing long-term follow-up studies in children with choledochal
      cysts.

PMID- 14689216
TI  - Six cases of children with a benign cervical tumor who required tracheostomy.
AB  - Cervical tumors sometimes cause airway obstruction. We have treated six children
      with benign cervical tumors who required tracheostomy. Two cervical and one
      glossal lymphangiomata treated with local injection of OK432 after creating a
      tracheostomy were successfully decannulated after the treatment. One patient with
      a giant cervical lymphangioma needed an EXIT (ex utero intrapartum treatment)
      procedure. He underwent tracheostomy at 10 months of age after long-term
      endotracheal intubation, but he died of sepsis and hypoxic brain damage at 18
      months. One patient with a subglottic hemangioma treated with steroids finally
      achieved closure of the tracheostomy at 2 years of age. A 7-year-old girl with a
      tracheal schwannoma underwent tracheostomy performed a week after admission, but
      she already had hypoxic brain damage resulting from problems with intubation.
      Most patients with a lymphangioma or hemangioma in the cervical region have
      required early tracheostomy before commencing treatment with OK-432 or steroids.
      If there is any sign of possible airway compromise, then it is vital to perform
      an early tracheostomy, even for benign tumors.

PMID- 14689217
TI  - Ilio-psoas abscess caused by methicillin-resistant Staphylococcus aureus (MRSA):
      a rare but potentially dangerous condition in neonates.
AB  - We report a case of methicillin-resistant Staphylococcus aureus ilio-psoas
      abscess (IPA) in a neonate. This case has clinical importance because this
      neonate had toxic shock syndrome-like exanthematous disease, known as NTED,
      before developing IPA. A high index of suspicion is required for IPA if a neonate
      presents with limb disuse and fever of unknown origin. Our case required surgical
      drainage, since ultrasound-guided percutaneous needle aspiration failed.

PMID- 14689218
TI  - Paediatric anal endosonography.
AB  - PURPOSE: This study was performed to determine the endosonographic features of
      the anal canal in normal children and to compare these findings with the
      endosonographic features in children with congenital anorectal malformations.
      METHODS: Two groups of children were examined by anal endosonography (AES): group
      1 ( n=30) were controls, and group 2 ( n=15) were children born with anorectal
      malformations. RESULTS: In the normal group, the sphincter elements were clearly
      visualised. The intersphincteric plane produced a double image, which differs
      from the adult appearance. Of 15 patients who had anorectoplasty, AES identified
      accurate placement of the neoanus within the sphincters in 13 and slight
      malposition in two patients. CONCLUSIONS: This study details the endosonographic
      appearances of the anal canal in healthy children aged from 1 month to 14 years.
      AES provided useful anatomical detail in patients following anorectoplasty.

PMID- 14689219
TI  - Endoscopic aqueductoplasty: stent or not to stent?
AB  - OBJECTIVE: The aim of this study is to evaluate if the long-term interventricular
      communication following aqueductoplasty is determined by the etiology of the
      aqueductal stenosis (AS). METHODS: We retrospectively analyzed 27 patients who
      underwent endoscopic aqueductoplasty or endoscopic interventriculostomy with or
      without a stent for the treatment of AS or isolated fourth ventricle. Surgeries
      were performed between July 1997 and June 2003. Mean age at the time of surgery
      was 8 years. Mean follow-up is 24 months. RESULTS: We divided the patients into
      three groups. Group 1 consisted of 5 patients with membranous distal AS. Four
      patients were sufficiently treated by aqueductoplasty alone and 1 asymptomatic
      restenosis occurred. Group 2 consisted of 4 patients with AS due to a
      periaqueductal tumor. Three patients underwent aqueductoplasty and tumor biopsy
      with subsequent restenosis of the aqueduct. One patient underwent aqueductoplasty
      with a stent and tumor biopsy at the same time. Group 3 consisted of 18 patients
      with isolated fourth ventricle. The initial surgery was successful in 11
      patients. Seven patients required revisions. CONCLUSION: The long-term
      communication following aqueductoplasty is determined by the etiology and
      morphology of the AS. In patients with a membranous distal AS aqueductoplasty
      alone will suffice. In patients with tumor-associated AS aqueductoplasty alone
      will not stay open. Those patients would better be treated with third
      ventriculostomy. In patients with isolated fourth ventricle the risk of
      restenosis is high. Therefore, we favor primary stent placement.

PMID- 14689220
TI  - A comparison of responses from olfactory receptor neurons of Heliothis subflexa
      and Heliothis virescens to components of their sex pheromone.
AB  - Single-cell electrophysiological recordings were obtained from olfactory receptor
      neurons in sensilla trichodea on male antennae of the heliothine species
      Heliothis subflexa and the closely related congener H. virescens. A large
      percentage of sensilla (72% and 81%, respectively, of all sensilla sampled)
      contained a single odor-responsive receptor neuron tuned to the major pheromone
      component of both species, Z-11-hexadecenal. A second population of sensilla on
      H. subflexa antennae (18%) housed receptor neurons that were tuned to Z-9
      hexadecenal but also responded with less sensitivity to Z-9-tetradecenal. A
      similar population of sensilla (4%) on H. virescens male antennae housed receptor
      neurons that were shown to be tuned specifically only to Z-9-tetradecenal, with
      no response to even high dosages of Z-9-hexadecenal. A third population of
      sensilla (comprising 8% and 16% of the sensilla sampled in H. subflexa and H.
      virescens, respectively) housed two olfactory receptor neurons, one of which was
      tuned to Z-11-hexadecenyl acetate and the other tuned to Z-11-hexadecenol. In H.
      subflexa the Z-11-hexadecenyl acetate-tuned neuron also responded to Z-9
      tetradecenal with nearly equivalent sensitivity. The behavioral requirements of
      males of these two species for distinct pheromonal blends was, therefore,
      reflected by the subtle differences in the tuning properties of antennal
      olfactory receptor neurons.

PMID- 14689221
TI  - Electrophysiological evidence for detection and discrimination of pheromonal bile
      acids by the olfactory epithelium of female sea lampreys ( Petromyzon marinus).
AB  - Electro-olfactograms were used to determine sensitivity and specificity of
      olfactory organs of female sea lampreys ( Petromyzon marinus) to four bile acids:
      3-keto petromyzonol sulfate and 3-keto allocholic acid from spermiating males and
      petromyzonol sulfate and allocholic acid from larvae. Spermiating male bile acids
      are thought to function as a mating pheromone and larval bile acids as a
      migratory pheromone. The response threshold was 10(-12) mol l(-1) for 3-keto
      petromyzonol sulfate and 10(-10) mol l(-1) for the other bile acids. At
      concentrations above 10(-9) mol l(-1), the sulfated bile acids showed almost
      identical potency, as did the non-sulfated bile acids. The two sulfated bile
      acids were more potent than the two non-sulfated ones. In addition, 3-keto
      petromyzonol sulfate and water conditioned with spermiating males induced similar
      concentration-response curves and response thresholds. Cross-adaptation
      experiments demonstrated that the sulfated and non-sulfated bile acids represent
      different odors to the olfactory epithelium of females. Further exploration
      revealed that 3-keto petromyzonol sulfate represents a different odor than
      petromyzonol sulfate, while 3-keto allocholic acid and allocholic acid represent
      the same odor. Results indicate that male-specific bile acids are potent and
      specific stimulants to the female olfactory organ, supporting the previous
      hypothesis that these bile acids function as a pheromone.

PMID- 14689223
TI  - Premalignant lesions of the kidney share the same genetics changes as
      conventional renal cell carcinoma.
AB  - This study investigated the frequency of allelic imbalance (AI) in particular
      loci in conventional renal cell carcinoma tissue and premalignant lesions of the
      kidney. DNA from the tumor tissue, premalignant lesions and normal kidney tissue
      of radical nephrectomy specimens from 33 patients was obtained. It was amplified
      with a set of eight microsatellite markers, which are located on chromosomes 2,
      3, 5, 8, 9, 11, 16, 17. AI in DNA samples was determined by analysis of the
      alteration in (CA)n repeats. The rates of AI in tumor tissue were found to be
      between 22.2% and 53.3% and in premalignant lesions between 11.1% and 40.0%.
      Premalignant lesions and tumor tissues in conventional renal cell carcinoma have
      the same genotypic changes in 50.0-87.8% (informative cases). These results
      suggest that the progressive accumulation of AI in areas of premalignant lesions
      may contribute to the development of renal cell carcinoma, representing an
      important molecular event in the multistep renal carcinogenesis cascade.

PMID- 14689222
TI  - Predictive medicine in non-malignant urological disorders.
AB  - The potential of disease prediction in non-malignant disorders should not be
      undervalued. Such disorders present several characteristics which make them
      suitable for disease prediction: they can be wide-spread, strongly affect the
      patients' quality of life, lead to a heavy burden on social health expenses and
      have a protracted clinical course. Moreover, people who present a high risk for
      non-malignant disease can be successfully introduced to long-term preventive
      measures such as lifestyle modifications, dietary changes and improvement in
      hygienic conditions. There is a growing demand for developing predictive medical
      strategies in urology. While urological cancers are the main focus of interest,
      we analyse the potentialities and challenges of predictive medicine in non
      malignant urological disorders, with particular attention to benign prostate
      hyperplasia and urolithiasis.

PMID- 14689224
TI  - Pain during transrectal ultrasonography guided prostate biopsy: a randomized
      prospective trial comparing periprostatic infiltration with lidocaine with the
      intrarectal instillation of lidocaine-prilocain cream.
AB  - Prostate biopsy is usually performed without anesthesia. We evaluated the
      patient's perception of pain/discomfort experienced during the procedure in terms
      of the type of anesthesia used: periprostatic infiltration with 2% lidocaine, or
      intrarectal instillation of lidocaine-prilocain cream. A total of 198 patients
      were divided into three groups: group 1 (control group, n=40) received
      sonographic gel intrarectally prior to biopsy, group 2 (n=75) were given
      intrarectal instillation of lidocaine-prilocain cream, and group 3 (n=80)
      received periprostatic anesthesia by injecting 10 ml of 2% lidocaine. Pain after
      each biopsy was assessed using an 11-point linear visual analog pain scale. The
      mean pain scores were 5.1 in group 1, 4.8 in group 2, and 2.5 in group 3,
      resulting in a significant difference between group 3 and both groups 1 and 2,
      but not between groups 1 and 2. The incidence of biopsy-related adverse events
      did not differ among groups. Transrectal ultrasonographic guided periprostatic
      anesthesia is superior to intarectal instillation of lidocaine-prilocain cream.

PMID- 14689225
TI  - Environmental exposure, chlorinated drinking water, and bladder cancer.
AB  - Environmental and/or occupational factors have been proposed to play a critical
      role in urological malignancies and, in particular, in bladder cancer.
      Epidemiological studies have demonstrated with sufficient evidence that factors
      such as smoking and exposure to aromatic amines, paints and solvents, leather
      dust, inks, some metals, polycyclic aromatic hydrocarbons, combustion products,
      or diesel exhaust fumes are associated with the development of bladder cancer.
      Candidates with an uncertain potential for inducing this type of cancer include
      dietary factors, specifically fats and cholesterol, and the exposure to
      contaminants in drinking water. This chapter will describe and discuss the
      respective literature on environmental and occupational factors linked to
      carcinogenesis in bladder cancer. For several reasons, the potential effects of
      tea and coffee consumption will also be considered. A solid epidemiological
      evaluation of environmental and occupational factors linked to carcinogenesis has
      to meet many challenges: the number of confounding factors is often large,
      exposure needs to be determined retrospectively, and elevation of the
      attributable risk is low in most cases. In view of the long-term exposure of the
      vast majority of the population to, for instance, drinking- water contaminants,
      however, the impact of even small elevations of risk warrants evaluation. This
      complex task needs comprehensive approaches on a large scale including modern
      analytical, molecular biological and epidemiological methods.

PMID- 14689226
TI  - Mediastinal lymphadenopathy in congestive heart failure: a sequential CT
      evaluation with clinical and echocardiographic correlations.
AB  - The aim of this study was to evaluate the frequency and evolution after treatment
      of mediastinal lymphadenopathy associated with congestive left heart failure on
      CT scans in correlation with clinical and echocardiographic findings. Thirty-one
      consecutive patients with subacute left heart failure underwent a clinical
      evaluation using the NYHA classification, a CT examination, and transthoracic
      echocardiography at the time of initial presentation (T1). After initiation of
      medical treatment (T2), follow-up CT scans were systematically obtained together
      with a clinical evaluation. At T1, all patients showed severe (type III: n=12,
      39%; type IV: n=12, 39%) to moderate (type I, n=1, 3%; type II, n=6, 19%) dyspnea
      with a mean ejection fraction of 39% (range 22-74%). On initial CT scans,
      enlarged mediastinal lymph nodes were seen in 13 patients (42%) with blurred
      contours in 5 patients (16%) and hazy mediastinal fat in 1 patient (3%).
      Significant decrease in the size of lymphadenopathy was observed between T1 and
      T2 (T1, n=13, 42% vs T2, n=10, 32%; p<0.05) with a concurrent decrease in the
      severity of dyspnea (grade III-IV dyspnea at T1, n=24, 78% vs grade I-II dyspnea
      at T2, n=26, 83.5%). Patients with enlarged lymph nodes at T1 showed: (a) a
      significantly lower ejection fraction at echocardiography than those without
      lymphadenopathy (mean+/-SD value: 34+/-12.9 vs 43+/-13.8%; p=0.04); (b) a
      significantly larger diameter of the right superior pulmonary vein (mean+/-SD
      value: 17+/-2.75 vs 14+/-3.9 mm; p=0.04); and (c) a higher frequency of abnormal
      peribronchovascular thickening ( n=5 vs n=1; p=0.06). Mediastinal lymphadenopathy
      associated with subacute left heart failure was observed in 13 patients (42%),
      showing regression after initiation of treatment in 8 of 13 patients (62%).

PMID- 14689227
TI  - Non-invasive 16-row multislice CT coronary angiography: usefulness of saline
      chaser.
AB  - The aim of this study was to investigate the usefulness of saline chaser in 16
      row multislice CT (16-MSCT) coronary angiography. Forty-two patients were divided
      into two groups for contrast material (CM) administration: group 1 (140 ml at 4
      ml/s) and group 2 (100 ml at 4 ml/s followed by 40 ml of saline chaser at 4
      ml/s). All patients underwent retrospectively ECG-gated 16-MSCT coronary
      angiography. The attenuation at the origin coronary vessels was assessed. Three
      regions of interest (ROIs) were drawn throughout the data set: (a) ascending
      aorta (ROI 1); (b) descending aorta (ROI 2); and (c) pulmonary artery (ROI 3).
      The attenuation in the superior vena cava was recorded (ROI 4). The average
      attenuation and the slope were calculated in each ROI and differences were
      assessed with a Student's t test. The average attenuation in the coronary vessels
      was not significantly different in the two groups. The average attenuations in
      ROI 1 were 325 and 327 HU, in ROI 2 were 328 and 329 HU and in ROI 3 were 357 and
      320 HU, for groups 1 and 2, respectively (p>0.05). The slopes in ROI 1 were -0.2
      and 1.1, in ROI 2 were 2.8 and 2.1 (p>0.05) and in ROI 3 were 3.9 and -9.0
      (p<0.05), for groups 1 and 2, respectively. The average attenuations in ROI 4
      were 927 and 643 HU (p<0.05), for groups 1 and 2, respectively. One hundred
      milliliters of CM with 40 ml of saline chaser provides the same attenuation as
      140 ml of CM (35% less) with decreased hyper-attenuation in the superior vena
      cava.

PMID- 14689228
TI  - Intravascular papillary endothelial hyperplasia of the extremities: MR imaging
      findings with pathologic correlation.
AB  - We report the MRI findings of three cases of intravascular papillary endothelial
      hyperplasia (IPEH) of the extremities with correlation of the pathologic
      findings. The IPEH is a non-neoplastic reactive lesion within the vessels and is
      commonly associated with thrombi. Signal intensity of the IPEH is complex due to
      the thrombi and the PEH itself. The thrombi are characterized by a slightly
      hyperintense signal on T1- and T2-weighted images compared with that of muscle
      when it comes at the medium stage of hemorrhage. Papillary endothelial
      hyperplastic tissue appears either as iso- or hyperintense to the muscle on T2-
      and T1-weighted images and shows variable enhancement on Gd-DTPA-enhanced images.

PMID- 14689229
TI  - Multidetector-row cardiac CT: diagnostic value of calcium scoring and CT coronary
      angiography in patients with symptomatic, but atypical, chest pain.
AB  - The aim of this study was to investigate the accuracy of multidetector-row
      cardiac CT (MDCT), calcium scoring (Ca-Sc), and MDCT coronary angiography (MD
      CTA) in the assessment of coronary atherosclerosis. Thirty-eight patients
      underwent invasive coronary angiography (CA) and MDCT (collimation 4x1 mm, pitch
      1.5 mm, TI 500 ms, 120 kV, 300 mAs, and retrospective ECG-gating). Calcium
      scoring was calculated for the total coronary artery territory and for RCA, LCA,
      and LCX separately. The MD CTA served to assess the degree and the localization
      of stenoses. All findings were compared to invasive coronary angiography.
      Approximately 68.4% (390 of 570) of all coronary segments could be visualized by
      MDCT. Correlation coefficient for MD CTA and CA amounted to r=0.58, showing
      distinct differences for the individual segments. Proximal segments generally
      showed better correlation (range 0.81-0.77) than medial segments (range 0.91
      0.20), distal segments (range 0.55-0.04), or side branches (range 0.76-0.00).
      Patients with hemodynamically relevant (>75%) stenoses were detected by MD CTA
      with 72.2% sensitivity (13 of 18) and 100% specificity (20 of 20). For Ca-Sc
      sensitivity ranged between 94.7% (17 of 18) and 66.7% (12 of 18), specificity
      between 20% (4 of 20) and 80% (16 of 20) respectively, depending on the
      prevailing cutoff value. Combination of both methods led to 83.3% sensitivity (15
      of 18) and 100% specificity (20 of 20), reaching no level of significance as
      compared with Ca-Sc (p=0.73) or MD CTA (p=0.23) alone. Calcium scoring as a
      single method showed highest sensitivity in the detection of coronary
      atherosclerosis but at the expense of low specificity. In patients with no or
      moderate calcifications, combination with MD CTA helped to distinctly increase
      specificity and NPV.

PMID- 14689230
TI  - Free radicals and antioxidants in primary fibromyalgia: an oxidative stress
      disorder?
AB  - The role of free radicals in fibromyalgia is controversial. In this study, 85
      female patients with primary fibromyalgia and 80 age-, height-, and weight
      matched healthy women were evaluated for oxidant/antioxidant balance.
      Malondialdehyde is a toxic metabolite of lipid peroxidation used as a marker of
      free radical damage. Superoxide dismutase is an intracellular antioxidant enzyme
      and shows antioxidant capacity. Pain was assessed by visual analog scale. Tender
      points were assessed by palpation. Age, smoking, body mass index (BMI), and
      duration of disease were also recorded. Malondialdehyde levels were significantly
      higher and superoxide dismutase levels significantly lower in fibromyalgic
      patients than controls. Age, BMI, smoking, and duration of disease did not affect
      these parameters. We found no correlation between pain and number of tender
      points. In conclusion, oxidant/antioxidant balances were changed in fibromyalgia.
      Increased free radical levels may be responsible for the development of
      fibromyalgia. These findings may support the hypothesis of fibromyalgia as an
      oxidative disorder.

PMID- 14689231
TI  - The efficacy of the combination therapy of 5-fluorouracil, cisplatin and
      leucovorin for hepatocellular carcinoma and its predictable factors.
AB  - PURPOSE: Several clinical trials in human neoplasms have demonstrated the
      effectiveness of combination therapy with 5-fluorouracil (FUra), cisplatin
      (CDDP), and leucovorin (LV). Thymidylate synthase (TS), the target enzyme of
      FUra, and dihydropyrimidine dehydrogenase (DPD), the rate-limiting catabolic
      enzyme of pyrimidines, have both been reported to be predictors of the response
      to FUra-based chemotherapies. Therefore, we aimed to clarify the effects of a
      combination of the three drugs against hepatoma cells and to determine the role
      of these two enzymes using in vitro models. METHODS: Five human hepatoma cell
      lines (Hep3B, HepG2, HuH7, PLC/PRF/5 and Chang) were used. Cytotoxicity was
      determined after exposure to various concentrations and combinations of antitumor
      agents. The combination effects of FUra and CDDP in terms of synergy, additivity
      or antagonism were evaluated by median effect analysis. The mRNA levels of TS and
      DPD were measured by quantitative real-time PCR. Expression of TS and DPD
      proteins was also investigated. RESULTS: LV alone did not show any cytotoxicity,
      although it enhanced the cytotoxicity of FUra, but not that of CDDP. Synergistic
      enhancement was observed with the combination of FUra and CDDP against all cells.
      The median combination index at fraction 0.5 was 0.554 (range 0.273-0.616). All
      cells expressed TS and DPD with median relative quantities of mRNA normalized to
      that of HuH7 cells of 1.04 (range 1.00-1.32) and 1.18 (range 0.88-1.55),
      respectively. A strong correlation was found between the IC(50) of FUra and the
      mRNA level of DPD (r=0.912, P=0.0295). CONCLUSIONS: LV and CDDP enhanced the
      cytotoxicity of FUra, which provided a rationale for the regimen combining the
      three drugs for the treatment of hepatocellular carcinoma. DPD plays an important
      role in the sensitivity to FUra, and the DPD mRNA expression level may be used to
      predict the response to FUra-based chemotherapy for HCC.

PMID- 14689232
TI  - Pulmonary nocardiosis in a patient with CML relapse undergoing imatinib therapy
      after bone marrow transplantation.
AB  - We describe a case of pulmonary nocardiosis in a female patient with graft-versus
      host disease (GVHD) underwent therapy with imatinib mesylate for a relapse of
      chronic myeloid leukemia (CML) after allogeneic bone marrow transplantation
      (BMT). The patient developed chronic GVHD 8 months after the use of imatinib and
      was on corticosteroid therapy. Three months after the development of chronic
      GVHD, she acquired pulmonary nocardiosis and a computed tomography (CT) scan of
      the chest showed multiple nodular lesions with cavitations over both lungs. She
      was successfully treated with single-agent trimethoprim-sulfamethoxazole
      (TMP/SMX) and the infection did not recur. Our case indicated that pulmonary
      nocardiosis could occur in patients with GVHD undergoing imatinib and
      corticosteroid therapy and might be treated by single-agent TMP/SMX.

PMID- 14689233
TI  - Fatal deep vein thrombosis after allogeneic reduced intensity hematopoietic stem
      cell transplantation for the treatment of metastatic gastric cancer.
AB  - A 61-year-old man received reduced intensity stem cell transplantation (RIST) for
      the treatment of metastatic gastric cancer. The cytoreductive course of RIST was
      uneventful until day 0, when fever suddenly developed and his performance status
      deteriorated. Edema developed in the bilateral lower extremities by day 7, which
      was diagnosed by Doppler ultrasonography as deep vein thrombosis (DVT) involving
      the femoral veins to the inferior vena cava. While the edema improved with
      anticoagulation treatment, gastrointestinal graft-versus-host disease (GVHD)
      followed on day 13. Diarrhea subsided spontaneously, but hypoalbuminemia
      persisted, with the subsequent development of oliguria and jaundice on day 18. He
      died of sepsis on day 30, without any evidence of cancer progression. This case
      demonstrates that DVT is a potentially significant problem following RIST for
      solid tumors.

PMID- 14689234
TI  - Fatal hemorrhagic pneumonia caused by infection due to Kytococcus sedentarius--a
      pathogen or passenger?
AB  - A 55-year old man developed a hemorrhagic pneumonia, likely due to infection with
      Kytococcus sedentarius during neutropenia following induction chemotherapy for
      acute myeloid leukemia. Severe mucosal barrier injury and the selective pressure
      of broad-spectrum antibiotics probably made it possible for this normally
      harmless commensal to penetrate the gut, spread through the blood stream, and
      invade the lungs.

PMID- 14689236
TI  - Remission induced by Campath-1H for thymoma-associated agranulocytosis.
AB  - Thymoma-associated agranulocytosis is a rare but almost universally fatal
      condition. Reports to date have described several immunosuppressive therapies
      including steroids, cyclophosphamide and vincristine as adjuvants to thymectomy,
      in an effort to improve neutropenia. We report the response to the monoclonal
      antibody Campath-1H of a patient with a thymoma and associated agranulocytosis
      with complete absence of bone marrow granulocyte precursors, which had failed to
      respond to thymectomy. Treatment with Campath-1H resulted in complete responses
      of promising durability sustained with the addition of cyclosporin and
      mycophenolate mofetil as maintenance therapy.

PMID- 14689237
TI  - The role of cephalo-condylic nailing of the proximal femur in terms of the basic
      stability of inter-trochanteric fractures.

PMID- 14689239
TI  - Identification of tumor antigens and T-cell epitopes, and its clinical
      application.
AB  - The capability of antigen-specific CD8(+) and CD4(+) T lymphocytes to mediate
      antitumor immunity has generated remarkable interest in the identification of
      target antigens and their epitopes. The classical strategy to define tumor
      antigens is based on the employment of in vivo sensitized tumor-reactive T
      lymphocytes from cancer patients. These lymphocytes are used to screen an
      autologous tumor cDNA expression library for the target antigen. Alternatively,
      antibodies from the serum of cancer patients can be applied to screen a tumor
      derived phage expression library for immunogenic cellular structures. In
      addition, potential target antigens have been selected by gene expression
      profiling searching for overexpressed gene products in neoplastic cells compared
      with normal tissues. B-cell target structures and overexpressed gene products
      have to be verified as T-cell antigens by the strategy of "reverse immunology."
      Therefore, T cells are sensitized in vitro by autologous dendritic cells loaded
      with predicted antigenic peptide ligands for a given HLA allele or with the
      global antigen. These different approaches led to the identification of a still
      growing number of antigenic peptides providing the basis for the development of
      new active and passive immunotherapies and for the monitoring of spontaneous and
      vaccine-induced T-cell responses. Some of these antigens and/or their epitopes
      are now validated in different clinical regimens for their capability to mediate
      potent T-cell immunity in cancer patients.

PMID- 14689240
TI  - Heat shock proteins: biological functions and clinical application as
      personalized vaccines for human cancer.
AB  - Heat shock proteins (HSPs) are a large family of proteins with different
      molecular weights and different intracellular localizations. These proteins
      undertake crucial functions in maintaining cell homeostasis, and therefore they
      have been conserved during evolution. Hsp70 and Grp94/gp96, due to their peptide
      chaperone capacity and their ability to actively interact with professional
      antigen-presenting cells (APCs), are also endowed with crucial immunological
      functions. The immunological properties of these proteins and their implications
      for vaccine in human cancer will be discussed. Immunological and clinical data of
      phase I/II studies in melanoma and colorectal cancer patients will be reviewed.

PMID- 14689241
TI  - Non-invasive assessment of distribution volume ratios and binding potential:
      tissue heterogeneity and interindividually averaged time-activity curves.
AB  - Due to the stochastic nature of radioactive decay, any measurement of
      radioactivity concentration requires spatial averaging. In pharmacokinetic
      analysis of time-activity curves (TAC), such averaging over heterogeneous tissues
      may introduce a systematic error (heterogeneity error) but may also improve the
      accuracy and precision of parameter estimation. In addition to spatial averaging
      (inevitable due to limited scanner resolution and intended in ROI analysis),
      interindividual averaging may theoretically be beneficial, too. The aim of this
      study was to investigate the effect of such averaging on the binding potential (
      BP) calculated with Logan's non-invasive graphical analysis and the "simplified
      reference tissue method" (SRTM) proposed by Lammertsma and Hume, on the basis of
      simulated and measured positron emission tomography data [[(11)C] d- threo
      methylphenidate (dMP) and [(11)C]raclopride (RAC) PET]. dMP was not quantified
      with SRTM since the low k(2) (washout rate constant from the first tissue
      compartment) introduced a high noise sensitivity. Even for considerably different
      shapes of TAC (dMP PET in parkinsonian patients and healthy controls,
      [(11)C]raclopride in patients with and without haloperidol medication) and a high
      variance in the rate constants (e.g. simulated standard deviation of K(1)=25%),
      the BP obtained from average TAC was close to the mean BP (error <5%). However,
      unfavourably distributed parameters, especially a correlated large variance in
      two or more parameters, may lead to larger errors. In Monte Carlo simulations,
      interindividual averaging before quantification reduced the variance from the
      SRTM (beyond a critical signal to noise ratio) and the bias in Logan's method.
      Interindividual averaging may further increase accuracy when there is an error
      term in the reference tissue assumption E= DV(2)- DV' ( DV(2) = distribution
      volume of the first tissue compartment, DV' = distribution volume of the
      reference tissue). This can be explained by the fact that the distribution volume
      ratio ( DVR= DV/DV') obtained from averaged TAC is an approximation for Sigma
      DV/Sigma DV' rather than for Sigma DVR/ n. We conclude that Logan's non-invasive
      method and SRTM are suitable for heterogeneous tissues and that discussion of
      group differences in PET studies generally should include qualitative and
      quantitative assessment of interindividually averaged TAC.

PMID- 14689243
TI  - The acrophysis: a unifying concept for understanding enchondral bone growth and
      its disorders. II. Abnormal growth.
AB  - In order to discuss and illustrate the effects common to normal and abnormal
      enchondral bone at the physes and at all other growth plates of the developing
      child, the term "acrophysis" was proposed. Acrophyses include the growth plates
      of secondary growth centers including carpals and tarsals and apophyses, and the
      growth plates at the nonphyseal ends of small tubular bones. Abnormalities at
      acrophyseal sites are analogous to those at the physeal growth plates and their
      metaphyses. For example, changes relating to the zone of provisional
      calcification (ZPC) are often important to the demonstration of such
      similarities. Lead lines were an early example of the concept of analogy from
      abnormality due to physeal and to acrophyseal disturbance. The ZPC is a key
      factor in understanding patterns of rickets and its healing. Examples (including
      hypothyroidism, scurvy and other osteoporosis, Ollier disease, achondroplasia,
      and osteopetrosis, as well as the family of frostbite, Kashin-Beck disease, and
      rat bite fever) illustrate the acrophysis principle and in turn their
      manifestations are explained by that principle.

PMID- 14689242
TI  - Feasibility of sodium/iodide symporter gene as a new imaging reporter gene:
      comparison with HSV1-tk.
AB  - Positron emission tomography (PET) imaging reporter genes, such as HSV1-tk and
      D(2) receptor genes, make it possible to visualise gene expression non-invasively
      and repetitively in vivo. However, these systems require the synthesis of
      complicated substrates and the availability of expensive PET equipment.
      Expression of the sodium/iodide symporter ( NIS) gene can be easily monitored
      with radioiodines and technetium-99m using a gamma camera. To evaluate the
      possibility of using NIS as an imaging reporter gene, we compared its
      characteristics with those of the conventional HSV1-tk gene. The CM cell line was
      made by transfecting the HSV1-tk gene into CT-26 (mouse colon carcinoma cell
      line). The CTN and CMN cell lines were then made by transfecting the NIS gene
      into CT-26 and CM. We measured the uptake of iodine-125 iodovinyldeoxyuridine
      ([(125)I]IVDU) and (125)I to evaluate the expression of the HSV1-tk and NIS
      genes, respectively. Each cell line was injected into four flank sites in Balb/c
      mice. The biodistribution study was performed after intravenously injecting
      [(125)I]IVDU and (131)I, and (131)I scintigraphy was performed for the evaluation
      of NIS expression. In vitro studies indicated that CTN and CMN had 40- to 79-fold
      and 150- to 256-fold higher uptake of (125)I than CT-26 and CM, respectively.
      Furthermore, CM and CMN showed 57- to 69-fold higher uptake of [(125)I]IVDU than
      CT-26 and CTN. NIS gene expression and (125)I accumulation were found to be
      directly correlated ( R(2)=0.923), as were HSV1-tk gene expression and
      [(125)I]IVDU accumulation ( R(2)=0.956). Calculated signal per unit NIS and HSV1
      tk mRNA expression was 23,240+/-3,755 cpm and 34,039+/-5,346 cpm, respectively.
      In vivo study indicated that CTN and CMN had 2.3- and 5.8-fold higher uptake of
      (131)I than CT-26 and CM, and 1.8- and 3.5-fold higher uptake of [(125)I]IVDU
      than CT-26 and CTN. Scintigraphy using (131)I easily visualised CTN and CMN
      tumours. In conclusion, the NIS gene may be viewed as an imaging reporter gene
      with comparable performance to the HSV1-tk gene for monitoring target gene
      expression.

PMID- 14689244
TI  - Enantioselective transesterification using lipase-displaying yeast whole-cell
      biocatalyst.
AB  - An enantioselective transesterification in non-aqueous organic solvent was
      developed by utilizing a lipase-displaying yeast whole cell biocatalyst
      constructed in our previous study. As a model reaction, optical resolution of
      (RS)-1-phenylethanol, which serves as one of chiral building blocks, was carried
      out by enantioselective transesterification with vinyl acetate. Recombinant
      Rhizopus oryzae lipase displayed on the yeast cell surface retained its activity
      in hexane, heptane, cyclohexane and octane. The effective amount of whole-cell
      biocatalyst in the reaction mixture was 10 mg/ml solvent. In a reaction mixture
      incubated for 36 h with molecular sieves 4A, the concentration of (R)-1
      phenylethyl acetate reached 39.8 mM (97.3% yield) with high enantiomeric excess
      (93.3%ee). In contrast, a reaction mixture incubated without molecular sieves 4A
      produced little (R)- and (S)-1-phenylethyl acetate. The results obtained in this
      study demonstrate the applicability of the lipase-displaying yeast whole cell
      biocatalyst to bioconversion processes in non-aqueous organic solvents.

PMID- 14689245
TI  - The relative glucose uptake abilities of non-Saccharomyces yeasts play a role in
      their coexistence with Saccharomyces cerevisiae in mixed cultures.
AB  - The growth and glucose uptake of single cultures of the wine-related yeasts
      Kluyveromyces thermotolerans, Torulaspora delbrueckii, and Saccharomyces
      cerevisiae were investigated. The yeasts had different specific glucose uptake
      rates (qs) that depended on the residual glucose concentration and the oxygen
      availability. In mixed cultures, the qs values of the yeasts were not subject to
      any interaction effects over a wide range of glucose concentrations. Our results
      strongly indicate that the relative glucose uptake abilities of both non
      Saccharomyces yeasts, i.e. the qs(non-Saccharomyces)/qs(S. cerevisiae) ratios,
      regulated their abilities to compete for space in mixed cultures with S.
      cerevisiae, which, in turn, regulated their early deaths. This hypothesis enabled
      us to explain why K. thermotolerans was less able than T. delbrueckii to coexist
      with S. cerevisiae in mixed cultures. Furthermore, it enabled us to explain why
      oxygen increased the abilities of K. thermotolerans and T. delbrueckii to coexist
      with S. cerevisiae in the mixed cultures.

PMID- 14689246
TI  - Avermectin: biochemical and molecular basis of its biosynthesis and regulation.
AB  - Avermectin and its analogues, produced by Streptomyces avermitilis, are major
      commercial antiparasitic agents in the field of animal health, agriculture, and
      human infections. They are 16-membered pentacyclic lactone compounds derived from
      polyketide and linked to a disaccharide of the methylated deoxysugar l
      oleandrose. Labeling studies, analyses of the biosynthetically blocked mutants,
      and the identification of the avermectin gene cluster allows characterization of
      most of the biosynthetic pathway. Recent completion of S. avermitilis genome
      sequencing is also expected to help in revealing the precise biosynthetic
      sequence and the complicated regulatory mechanism for avermectin biosynthesis,
      which has been long-awaited to be elucidated. The well characterized avermectin
      biosynthetic pathway and availability of S. avermitilis genome information in
      combination with the recent development of combinatorial biosynthesis should
      allow us to redesign more potent avermectin analogues and to engineer S.
      avermitilis as a more efficient host for the production of important commercial
      analogues.

PMID- 14689247
TI  - Behaviour of Mycobacterium sp. NRRL B-3805 whole cells in aqueous, organic
      aqueous and organic media studied by fluorescence microscopy.
AB  - The present work aimed at quantifying the viability and morphological changes
      occurring during the time course of the side-chain cleavage of beta-sitosterol,
      in aqueous, two-phase organic-aqueous and organic media by free resting cells of
      Mycobacterium sp. NRRL B-3805. The solvent used was bis(2-ethylhexyl) phthalate
      (BEHP). A 66.3% reduction in cell viability was observed after 24 h when the
      cells were incubated in phosphate buffer only, but the percentage of viable cells
      was constant thereafter. In biphasic systems with BEHP, cell viability was
      maintained at higher values in the first 48 h, during which complete degradation
      of substrate was achieved. The availability of oxygen, which should be higher in
      the biphasic system than in the aqueous system, and of a carbon and energy
      source, thus seem important for the cells to retain their viability. In biphasic
      systems, cells tended to shrink and decrease their surface roughness, i.e. to
      decrease their surface area, possibly as a way to protect themselves from
      mechanical stress due to the presence of organic-aqueous interfacial forces,
      which resulted in disaggregation of cell clusters. A method used to visualise
      BEHP droplets with a standard optical microscope showed that the cells adhered to
      the surface of the solvent droplets, but no cells were observed inside these. In
      pure BEHP medium, cells retained their viability level for at least 150 h,
      independently of a pre-incubation period, which did not seem to induce any
      adaptation effect. Solvent biocompatibility, higher oxygen availability and
      reduced interfacial stress could have contributed to this maintenance of
      viability.

PMID- 14689248
TI  - Divergence of mobile genetic elements involved in the distribution of xenobiotic
      catabolic capacity.
AB  - Bacteria adapt rapidly to environmental stimuli, such as exposure to xenobiotics.
      Mobile genetic elements (MGEs) play a major role in such bacterial adaptation,
      via the dispersal of catabolic capacity; and, in fact, genes that encode the
      degradation enzymes for xenobiotics are often located on MGEs. The list of
      reported catabolic MGEs keeps growing as researchers continue to isolate and
      characterize xenobiotic degraders and the corresponding catabolic genes. Major
      catabolic MGEs include (conjugative) plasmids, transposons, and conjugative
      transposons. Catabolic transposons can be divided into class I elements
      (composite transposons) and class II elements (Tn 3 family transposons). This
      review includes a comprehensive list of naturally occurring discrete catabolic
      MGEs, together with a brief description for each. While MGEs are often rather
      large, genome-wide or large-scale sequence analyses have provided useful
      information on the whole genetic structure of MGEs, with clues to their function
      (transfer, maintenance, catabolism, etc.) and behavior in a complex natural
      environment. This review also gives an insight into MGE functions, based on the
      complete sequencing of several catabolic plasmids and two Pseudomonas genomes.

PMID- 14689249
TI  - Accumulation of astaxanthin and lutein in Chlorella zofingiensis (Chlorophyta).
AB  - When grown photoautotrophically, Chlorella zofingiensis strain CCAP 211/14
      accumulates a significant amount of valuable carotenoids, namely astaxanthin and
      lutein, of increasing demand for use as feed additives in fish and poultry
      farming, as colorants in food, and in health care products. Under standard batch
      culture conditions, this microalgal strain exhibits high values of both growth
      rate (about 0.04 h(-1)) and standing cell population (over 10(11) cells l(-1), or
      7 g dry weight l(-1)). Lutein, in a free (unesterified) form, was the prevalent
      carotenoid during early stages of cultivation (over 0.3 pg cell(-1), equal to 4
      mg g(-1) dry weight, or 20 mg l(-1) culture), whereas esterified astaxanthin
      accumulated progressively, to reach a maximum (over 0.1 pg cell(-1), equal to 1.5
      mg g(-1) dry weight, or 15 mg l(-1) culture) in the late stationary phase. A
      differential response of lutein and astaxanthin accumulation was also recorded
      with regard to the action of some environmental and nutritional factors. C.
      zofingiensis CCAP 211/14 represents a unique model system for analyzing the
      differential regulation of the levels of primary (lutein) and secondary
      (astaxanthin) carotenoids. Relevant also from the biotechnological viewpoint,
      this photosynthetic organism, with outstanding attributes for fast photosynthetic
      growth and carotenoid accumulation, might prove most valuable for its application
      to the mass production of either or both lutein and astaxanthin.

PMID- 14689250
TI  - Molecular cloning and expression of the pyranose 2-oxidase cDNA from Trametes
      ochracea MB49 in Escherichia coli.
AB  - A cDNA of a structural gene encoding pyranose 2-oxidase (P2O) from Trametes
      ochracea strain MB49 was cloned into Escherichia coli strain BL21(DE3) on a
      multicopy plasmid under the control of the trc promoter. Synthesis of P2O was
      studied in batch cultures in LB or M9-based mineral medium at 28 degrees C. While
      there was a low specific activity of P2O in LB medium, the enzyme was synthesised
      constitutively in mineral medium and represented 3% of the cell soluble protein
      (0.3 U mg(-1)). The effect of isopropyl beta-D-thiogalactoside on the expression
      of P2O was studied in mineral medium at 25 and 28 degrees C. The synthesis of P2O
      at 28 degrees C corresponded to 39% of the cell soluble protein but the major
      portion of P2O (93%) was in the form of non-active inclusion bodies (activity of
      P2O equalled 0.19 U mg(-1)). At 25 degrees C, the amount of P2O represented 14%
      of the cell soluble protein and the activity of P2O was 1.1 U mg(-1). The soluble
      enzyme represented 70% of the total amount of P2O.

PMID- 14689251
TI  - Pseudoaneurysm of the bulbourethral branch of the internal pudendal artery
      presenting as a urethral pseudodiverticulum in a child.
AB  - Pseudoaneurysm of the internal pudendal artery or its branches is a rare
      complication of pelvic trauma. It generally causes arteriocavernosal fistula
      leading to priapism. Connection between the urethra and the pseudoaneurysm has
      been documented in a few cases; however, pseudoaneurysm causing a urethral
      pseudodiverticulum has not been reported. We report a 7-year-old boy with a
      pseudoaneurysm of the bulbourethral branch of the left internal pudendal artery
      leading to a urethral pseudodiverticulum.

PMID- 14689252
TI  - MR imaging of calcifying aponeurotic fibroma of the thigh.
AB  - Calcifying aponeurotic fibroma is a rare, benign soft-tissue proliferation that
      occurs in the distal extremities in children. Because this lesion has a tendency
      to recur after surgical resection, MR imaging to determine the extent of the
      tumor for surgical planning is optimal. We report the MR findings in a 4-year-old
      boy with a calcifying aponeurotic fibroma of the thigh.

PMID- 14689254
TI  - Friedreich ataxia-update on pathogenesis and possible therapies.
AB  - Friedreich ataxia is the most-common inherited ataxia. Since the causative
      genetic basis was described in 1996, much has been learnt about the pathogenesis
      from human, animal, and yeast studies. This has led to the development of
      rational therapeutic approaches. In this review, the current state of knowledge
      regarding the pathogenesis of Friedreich ataxia is presented and possible
      therapeutic strategies based on this knowledge are discussed.

PMID- 14689256
TI  - A quantitative structure-antifungal activity relationship study of oxygenated
      aromatic essential oil compounds using data structuring and PLS regression
      analysis.
AB  - Twenty two oxygenated aromatic essential oil compounds were chosen for the study
      of the antifungal activity against two wood-decaying fungi, the white-rot
      Trametes versicolor, which mainly metabolizes lignin, and the brown-rot
      Coniophoha puteana, which digests cellulose in plant cell walls. Minimal
      inhibitory concentrations (MICs) were determined by the agar dilution method,
      using dimethyl sulfoxide (DMSO) as the solvent for the selected compounds and
      potato-dextrose agar (PDA) as the growth medium for both fungi. The MICs were
      then used to generate a tree structure, which represents the structuring of the
      essential oil compounds by the nature and position of the substituents in their
      aromatic rings, and as dependent variables (log(1/MIC)) in the QSAR analysis.
      Data structuring proved that a relationship between the molecular structures of
      the essential oil compounds and their antifungal activity exists, and the
      hypotheses derived therefrom were complemented by performing a QSAR analysis
      using the partial least squares (PLS) method. Statistically significant PLS
      models were obtained with the 1-octanol-water partition coefficient (C log P),
      the energy of the highest occupied molecular orbital (E(HOMO)), and the number of
      hydrogen-bond donor atoms in the molecules of the compounds studied (Donor) for
      T. versicolor and with C log P and the fractional negative surface area (FNSA1)
      for C. puteana.

PMID- 14689257
TI  - Posttraumatic stress symptoms after childhood cancer.
AB  - The posttraumatic stress model has recently been applied to understand the impact
      of life-threatening illness in adults and in children. From 1991 to 2001, 20
      studies have reported posttraumatic stress symptoms and/or posttraumatic stress
      disorder (PTSD) in childhood cancer survivors and/or their parents. A review of
      these studies is proposed. Prevalence of posttraumatic stress symptoms and/or
      PTSD in children and in their parents has been estimated, across studies, between
      2 and 20 % in survivors and between 10 and 30 % in their parents, even many years
      after the end of cancer treatment. Time elapsed since the diagnosis of cancer is
      usually not predictive of persistent symptoms. Subjective appraisal of life
      threat and illness beliefs are more important predictors than objective medical
      data. The presence of symptoms in survivors is not always related to that in
      their parents. The posttraumatic stress model renews the approach and
      understanding of psychopathological reactions of children with cancer, regarding
      trauma features and the role of parental responses. This model has important
      implications for individual and family clinical interventions. A reflection on
      the disruption of family functioning by childhood cancer (an example being bone
      marrow transplantation with a related donor) and on the recovery processes is
      needed.

PMID- 14689258
TI  - Prevalence and determinants of PTSD among Palestinian children exposed to
      military violence.
AB  - The prevalence and determinants of PTSD were assessed among 121 Palestinian
      children (6-16 years; 45% girls and 55% boys) living in the area of bombardment.
      The mothers (21-55 years) and the children themselves reported their exposure to
      military violence (being personally the target of violence or witnessing it
      towards others) and symptoms of posttraumatic stress disorders (PTSD: intrusion,
      avoidance and hypervigilance). The results showed that 54% of the children
      suffered from severe, 33.5 % from moderate and 11 % from mild and doubtful levels
      of PTSD. Girls were more vulnerable; 58% of them suffered from severe PTSD, and
      none scored on the mild or doubtful levels of PTSD. The child's gender and age,
      mother's education and PTSD symptoms were significant, and the exposure to
      traumatic experiences marginally significant determinants of children's PTSD
      symptoms. The most vulnerable to intrusion symptoms were younger girls whose
      mothers showed a high level of PTSD symptoms, whereas those most vulnerable to
      avoidance symptoms were children who had personally been targets of military
      violence and whose mothers were better educated and showed a high level of PTSD
      symptoms. The results are discussed in the context of military violence
      interfering with the protective function of family and home.

PMID- 14689259
TI  - Posttraumatic stress reactions among children following the Athens earthquake of
      September 1999.
AB  - The objective of the present study was to assess symptoms of posttraumatic stress
      disorder (PTSD), depression and anxiety among children 6 months after they had
      been exposed to an earthquake (EQ) affecting the northwestern suburbs of Athens
      in September 1999. A total of 115 children attending two elementary schools
      located at the epicentre of the EQ were assessed. A group of 48 children not
      affected by the EQ attending a school not affected by the EQ were used as
      controls. The children and their parents completed a number of questionnaires.
      Overall, there was a high rate (78%) of severe to mild PTSD symptoms in the EQ
      exposed group. Additionally, a substantial proportion of these children scored
      above criteria (32%) for depression compared to the control group (12.5%). Severe
      or moderate symptoms of PTSD were associated with high scores of depression (p =
      0.002). The relationship between PTSD symptoms and anxiety was limited to the
      "avoidance" factor of the anxiety questionnaire (p = 0.029). Those who were most
      likely to be affected were children alone at the time of the EQ, and children who
      sustained injuries. In summary, countries where EQs are frequent should be
      prepared to offer psychological support to a substantial proportion of children
      presenting with PTSD and depressive symptoms and should educate and prepare
      children to cope with these events.

PMID- 14689260
TI  - Dutch version of the Strengths and Difficulties Questionnaire (SDQ).
AB  - A Dutch translation of the Strengths and Difficulties Questionnaire (SDQ) was
      made. In the first wave of data collection, self-report data of 11- to 16
      yearolds (N = 970) were collected on the SDQ and other measures of
      psychopathology. In the second wave of data collection, extended versions of the
      SDQ were completed by 11- to 16-year-olds (N = 268), by parents of 8- to 16-year
      olds (N = 300) and by teachers of 8- to 12-year-olds (N = 208); in addition, the
      Child Behaviour Checklist (CBCL) was completed by the parents and the Youth Self
      Report (YSR) by the 11- to 16-year-olds. The results reveal that the internal
      consistency of the teacher SDQ is good; and the parent and self-report SDQ are
      generally acceptable and comparable with the internal consistencies of CBCL/YSR.
      The mean inter-informant product-moment correlations of the SDQ scales were
      satisfactory (parent-teacher 0.38; teacher-self-report 0.27; parent-self-report
      0.35) and comparable with the mean inter-informant correlations of the CBCL and
      YSR (0.34). The inter-informant rank correlations of the impact questions were
      also satisfactory (mean parent-teacher 0.48; mean parent-self-report 0.24).
      Concurrent validity with the other measures of psychopathology used in the
      present study was good.

PMID- 14689261
TI  - Is juvenile obsessive-compulsive disorder a developmental subtype of the
      disorder?--Findings from an Indian study.
AB  - Juvenile obsessive-compulsive disorder (OCD) has been hypothesized to be
      different from adult-onset OCD suggesting that juvenile OCD may be a
      developmental subtype of the disorder. There is some evidence that juvenile OCD
      may be phenotypically different from juvenile-onset adult OCD. This study
      examines the phenotypic characteristics of juvenile OCD (current age < or = 18
      years, n = 39), juvenile-onset adult OCD (onset < or = 18 years, current age >18
      years, n = 87) and adult-onset OCD (onset > 18 years, n = 105). Qualified
      psychiatrists expert in evaluating OCD subjects conducted clinical and structured
      interviews. In the multinomial logistic regression analysis, controlling for
      chronological age and gender, the juvenile OCD was associated with male
      preponderance, elevated rates of certain obsessive-compulsive symptoms, attention
      deficit hyperactivity disorder, chronic tics, body dysmorphic disorder and major
      depression. In addition, juvenile-onset adult OCD differed from juvenile OCD by
      having later age-at-onset and low rate of ADHD. The juvenile-onset adult OCD was
      positively associated with social phobia and chronic tics compared to adult-onset
      OCD. The juvenile OCD appears to be different from both juvenile-onset adult OCD
      and adult-onset OCD supporting previous observations that juvenile OCD could be a
      developmental subtype of the disorder.

PMID- 14689262
TI  - Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA)-
      results of a Danish field trial.
AB  - INTRODUCTION: Assessment of the effectiveness of clinical practice requires
      appropriate outcome measures. Health of the Nation Outcome Scales for Children
      and Adolescents (HoNOSCA) is a recently developed measure of outcome for use in
      child and adolescent mental health services (CAMHS). The aims of the present
      study were to evaluate sensitivity to change, face validity and clinical
      feasibility of HoNOSCA in a Danish field trial. METHOD: A prospective design in
      which HoNOSCA, Global Assessment of Psychosocial Disability (GAPD) and a
      clinician rated global outcome measure were completed at 15 field sites. 173
      patients were rated both at initial assessment and at follow-up after three
      months. RESULTS: HoNOSCA demonstrated satisfactory face validity. There was a
      strong correlation between HoNOSCA scores and GAPD scores ( r = 0.6, P < 0.001)
      and a highly significant association (ANOVA (F = 25.4, P < 0.001)) between change
      in HoNOSCA scores and global clinical ratings of change. Mean HoNOSCA scores
      varied between psychiatric diagnoses. CONCLUSIONS: HoNOSCA is a sensitive and
      valid measure of change for children and adolescents attending CAMHS.

PMID- 14689263
TI  - Deliberate self-harm in children and adolescents: association with social
      deprivation.
AB  - BACKGROUND: It has been demonstrated that adult suicidal behaviour is associated
      with unemployment and social deprivation. The association between self-harm and
      social deprivation in young people is less clear. AIMS: To examine the
      relationship between social deprivation and deliberate self-harm in children and
      adolescents in an UK district. METHOD: Computer records of patients under 18
      years of age presenting with self-harm at the district casualty department were
      analysed in Hull and East Yorkshire. The relationship with social deprivation was
      examined using Townsend scores. RESULTS: 730 young people presented with self
      harm during a period of two years. Socio-economic deprivation was associated with
      overdose, self-injury, and poisoning by illicit substances. After controlling for
      the proportion of single parent households, moving households with children, and
      adult long-term sickness in each ward, partial correlations remained significant
      between overdose, self-injury, and Townsend scores. CONCLUSIONS: The results
      highlight the importance of socio-economic deprivation in the aetiology of
      deliberate self-harm in young people. Primary and secondary prevention programs
      cannot be successful without taking this into consideration.

PMID- 14689264
TI  - How should we measure social disadvantage in clinic settings?
AB  - BACKGROUND: Despite a large research literature supporting their validity,
      deprivation indices derived from census data have not been routinely applied to
      clinic populations. METHOD: A case-note sample of 201 cases was examined, to
      identify whether such data (Jarman indices) predicted presenting disability
      separately from diagnostic class (behaviour, emotional, mixed, other, and no
      diagnosable disorder), or conventional clinic measures of social adversity (ICD
      10 psychosocial diagnostic codes). RESULTS: Jarman index scores predicted
      disability in behaviour disorders or other disorders. Conventional clinic
      measures of adversity predicted disability in mixed disorders. For emotional
      disorders, and those cases with no diagnosed disorder, clinically measured
      adversity and Jarman scores interacted. CONCLUSIONS: Postcode related census data
      capture information about clinic children's presenting disability that is not
      available from routine clinic assessment of psychosocial adversity. It should
      therefore be collected as part of the routine clinical child psychiatry
      assessment.

PMID- 14689272
TI  - Can genes transduced by adeno-associated virus vectors elicit or evade an immune
      response?
AB  - Vectors derived from the adeno-associated viruses (AAV) have been successfully
      used for the long-term expression of therapeutic genes in animal models and in
      patients. Stable expression of the transgene in the transduced cells can be used
      to correct disease stemming from genetic deficiencies. One of the major
      advantages of these vectors is reported to be the absence of deleterious immune
      responses following gene transfer. However, recent studies have shown that AAV
      vectors elicit humoral and cellular responses against the transgene products.
      This review article will focus on these two unique yet converse aspects of AAV:
      the ability to elicit host immune response to destroy target cells containing the
      transduced protein and the ability to evade immune response leading to stable
      expression of the transduced genes.

PMID- 14689273
TI  - Induction of interferon-inducible protein-10 and monokine induced by interferon
      gamma from human endothelial cells infected with Influenza A virus.
AB  - Primary human umbilical vein endothelial cells (HUVECs) were infected with
      Influenza virus A/Aichi/2/68 (H3N2) in order to determine the role of endothelial
      cells in mediating inflammation induced upon virus infection. Structural proteins
      of the virus and mRNA of the M2 protein were detected in the infected cells,
      indicating that virus infection had occurred in HUVECs. The Influenza A virus
      infected HUVECs showed elevated levels of gene expression of interferon (IFN)
      inducible protein (IP)-10 and monokine induced by IFN-gamma (Mig), while heat-,
      formalin- and diethyl ether-inactivated viruses did not enhance the IP-10 and Mig
      gene expression. The results thus indicate that infection of live Influenza A
      virus is responsible for elevation of IP-10 and Mig gene expression. The
      elevation of IP-10 and Mig gene expression in infected HUVECs was not accompanied
      by the elevation of IFN-gamma gene expression, indicating that the elevation of
      IP-10 and Mig gene expression was independent of the IFN-gamma pathway.

PMID- 14689274
TI  - Detection of ion channel activity in Xenopus laevis oocytes expressing Influenza
      C virus CM2 protein.
AB  - To demonstrate the ion channel activity of Influenza C virus CM2, we expressed
      this protein in oocytes of Xenopus laevis and measured whole cell currents by a
      two-electrode voltage-clamp method. It was found that the inward currents were
      induced upon hyperpolarizing the oocyte membranes. The amplitude of the currents
      increased slowly with time during the hyperpolarizing pulse, and the current
      voltage relationship was nonlinear, having a slope that increased with the level
      of hyperpolarization. These results suggest strongly that CM2 forms a voltage
      activated ion channel. The current amplitude was increased to a small extent by
      lowering the external pH. We also found that the anti-influenza A virus drug
      amantadine hydrochloride failed to attenuate the inward currents of CM2
      expressing oocytes induced by hyperpolarization. The reversal voltage of tail
      currents was affected by the reduction of [Cl-], but neither by the change of
      [Na+] nor by that of [K+]. Furthermore, the amplitude of the inward currents was
      decreased by an anion channel blocker. The data presented here suggest that CM2
      protein forms a voltage-activated ion channel permeable to chloride ion.

PMID- 14689275
TI  - High efficiency gene transfer into mammalian kidney cells using baculovirus
      vectors.
AB  - Gene delivery into kidney cells is essential to the development of gene therapy
      for nephropathy. This paper describes the use of baculovirus Autographa
      californica nucleopolyhedrovirus (AcMNPV) as a vector for gene delivery into
      several mammalian kidney cells. High-level expression of a reporter gene encoding
      for the green fluorescent protein (GFP) under a heterogonous promoter was
      observed in kidney cells from mouse, hamster, monkey, pig, and human. The level
      of transgene expression exhibited viral dose dependence and was enhanced by the
      addition of butyrate. Baculovirus transduction could also provided long-term
      target gene expression in kidney cell lines without cytotoxic effects. High
      efficiency transduction was also observed in primary mouse kidney cells. These
      results indicate that baculovirus can be used as a vector for kidney-directed
      gene transfer.

PMID- 14689276
TI  - Cell cycle perturbation in a human hepatoblastoma cell line constitutively
      expressing Hepatitis C virus core protein.
AB  - Hepatitis C virus (HCV) is one of the major causes of chronic liver disease with
      the potential for development of hepatocellular carcinoma (HCC). The core protein
      of HCV has been shown to modulate expression of various cellular genes and to
      influence a number of cellular functions. We investigated the effect of
      constitutively expressed HCV core protein on cell cycle progression in HepG2 cell
      line, which is derived from a differentiated human hepatoblastoma and shows
      biosynthetic features similar to human hepatocytes. The results indicated that
      stable expression of the core protein in unsynchronized HepG2 cells induced a
      perturbation of the cell cycle with reduced cell doubling meantime and increased
      S phase fraction. Increase of c-myc protein above the basal expression level was
      demonstrated with a significant increase of c-myc stability, as revealed by its
      prolonged intracellular half-life, in HepG2 expressing HCV core protein. In
      contrast, p53 and p21 levels were unchanged. These results suggest that HCV core
      protein may promote cell cycle progression in HepG2 cells possibly through
      increasing stability of c-myc oncoprotein. These results are in support of
      important role played by HCV core protein in virus-mediated pathogenesis in
      persistently infected hosts and in hepatocarcinogenesis.

PMID- 14689277
TI  - Fucosylated lactosamines participate in adhesion of HIV-1 envelope glycoprotein
      to dendritic cells.
AB  - Carbohydrates expressed on HIV-1 gp160 are purported to bind to several receptor
      types that affect virus pathophysiology. Here, we define a potential role for
      fucosylated glycans involved in the adhesion of cells expressing anchored HIV-1
      glycoprotein or HIV virions to human dendritic cells (DCs). We observe that a
      monoclonal antibody (FH6), with reactivity toward an extended dimeric form of a
      fucosyl lactosamine, binds to gp120 transfectants, blocking adhesion of these
      cells and virus particles to human DCs. We observe that serum antibodies induced
      by peptide mimetic of fucosylated carbohydrate core structures emulate the
      monoclonal antibody reactivity pattern, showing enhanced reactivity to HIV-1
      envelope-expressing cell line and blocking the adhesion of these cells to human
      DCs. These results suggest a potential role for initial adherence of virally
      infected cells or virions mediated by fucosylated lactosamines expressed on the
      envelope protein. As these carbohydrates function as adhesion molecules
      associated with homing and dissemination processes, such interactions may
      contribute to the HIV infection process.

PMID- 14689278
TI  - Mitochondrial HSP70, HSP40, and HSP60 bind to the 3' untranslated region of the
      Murine hepatitis virus genome.
AB  - We have previously shown that mitochondrial-aconitase binds specifically to the
      3' terminal 42 nucleotides of the Murine hepatitis virus (MHV) RNA along with
      three additional proteins of 70, 58 and 40 kDa to form a stable RNA-protein
      complex. Supershift and western blot assays have identified these three proteins
      as mitochondrial HSP70 (mtHSP70), HSP60, and HSP40. A series of co
      immunoprecipitation assays have established that these four MHV RNA binding
      proteins are associated, even in the absence of MHV RNA. However, the presence of
      a synthetic RNA containing the sequence bound by these four proteins does
      increase the amount of co-precipitated protein, in particular the amount of HSP60
      which is brought down with antibodies directed against HSP40 and mtHSP70. We have
      provided evidence for the interaction of these four proteins with the 3' end
      region of MHV RNA in infected cells by a series of immunoprecipitation RT-PCR
      assays. We believe it is likely that MHV RNA interacts with m-aconitase prior to
      its import into mitochondria in cooperation with extra-mitochondrial mtHSP70,
      HSP60, and HSP40.

PMID- 14689279
TI  - Codon usage bias amongst plant viruses.
AB  - An internet database (DPVweb) was established containing details of all sequences
      of viruses, viroids and satellites of plants that are complete or that contain at
      least one complete gene (n>4600). The start and end positions of each feature
      (genes, non-translated regions etc) were recorded and checked for accuracy.
      Client software was written to enable easy selection of sequences and features of
      a chosen virus and to analyse codon usage bias. Codon usage was analysed for each
      gene of one example of each fully-sequenced plant virus. There were large
      differences in codon preferences, related to the nucleotide composition of the
      genome, particularly the GC content of the third codon position. There was no
      effect of gene size on codon bias. Genes from the same genome usually had similar
      coding strategies except where constrained by the overlap of reading frames.
      Although some synonymous codons were consistently used with low frequency by both
      plants and viruses, viruses were not generally adapted to use (or avoid) those
      codons most frequently used by their host plants and there was no obvious
      association with the type of transmission. Mutational bias, rather than
      translational selection appears to account for the majority of the variation
      detected. The software is available at http://www.dpvweb.net/analysis/codons.php.

PMID- 14689280
TI  - Cucumber mosaic virus as carrier of a hepatitis C virus-derived epitope.
AB  - Cucumber mosaic virus (CMV) is a three component isodiametric plant virus which
      is common worldwide and has an extremely wide host range. A pseudorecombinant was
      made, derived from the RNA3 component of the CMV-S strain, carrying the coat
      protein (CP) gene, and the RNA1,2 components of the CMV-D strain. This system
      developed mild mosaic and vein clearing in Xanthi tobacco three weeks after
      inoculation. The CP gene was then engineered in three different positions, to
      encode a Hepatitis C virus (HCV) epitope. The selected peptide was the so-called
      R9 mimotope, a synthetic surrogate derived from a consensus profile of many
      hypervariable region 1 (HVR1) sequences of the putative HCV envelope protein E2.
      Serum samples from 60 patients with chronic hepatitis C displayed a significant
      immunoreactivity to crude plant extracts infected with the chimeric CMV. These
      results suggest that further investigation should be made into a possible vaccine
      function for the CMV-HCV mimotope system.

PMID- 14689281
TI  - Molecular characterization of a human rotavirus reveals porcine characteristics
      in most of the genes including VP6 and NSP4.
AB  - Long electropherotype with Subgroup I specificity is a common feature of animal
      rotaviruses. In an epidemic of infantile gastroenteritis in Manipur, India, long
      but SG I strains predominated in the outbreak in the year 1987-88. One such
      strain isolated from that region, following the outbreak had G9P [19]
      specificity. As this is a rare combination, the gene sequences encoding VP4, VP6,
      VP7, NSP1, NSP2, NSP3, NSP4 and NSP5 of this strain were analyzed. All these
      genes except VP7 were closely related to porcine rotaviruses (95-99% identity at
      amino acid level) and clustered with the porcine strains in phylogenetic
      analysis. In addition, it had subgroup I nature and belonged to NSP4 genotype B
      which is characteristic of animal rotaviruses. This is the first report of a
      rotavirus with VP6 and NSP4, two crucial proteins thought to be involved in host
      range restriction and pathogenicity, were of porcine origin and caused diarrhoea
      in a human host. Among the genes of this strain sequenced so far, only VP7 had
      highest identity to human strains at amino acid level. This study suggests
      reassortment may be occurring between human and other animal strains and some of
      the reassortant viruses may be virulent to humans.

PMID- 14689282
TI  - Effect of a single mutation in neuraminidase on the properties of Influenza B
      virus isolates.
AB  - Two strains of Influenza B virus were isolated in Vero cells. Subclones with
      improved efficiency of plaque formation were selected. The activity of the
      neuraminidase (NA) of the two subclones compared to their respective isolates
      dropped 20- and 100-fold, respectively. Both subclones had a common mutation in
      segment 6 leading to a change from Asp to Asn at position 457 in the NA. This
      mutation destroyed a salt bridge of the contact surface between the monomers,
      thereby causing the loss in enzymatic activity. The decreased NA activity caused
      improved plaque formation but had no significant impact on the replication in
      liquid culture.

PMID- 14689283
TI  - Nucleotide sequences of genome segments S6, S7 and S10 of Dendrolimus punctatus
      cypovirus 1.
AB  - The nucleotide sequences of genome segments S6, S7 and S10 of Dendrolimus
      punctatus cypovirus 1 Hunan I (DpCPV-HN(I)) and DpCPV-HN(I)-Se(3) (DpCPV-HN(I)
      passed three times in Spodoptera exigua) were determined. Segment S10 was 944
      nucleotides in length and encoded a polyhedrin of 248 amino acids (28,439 Da).
      Only two nucleotide mutations were found between DpCPV-HN(I) S10 and DpCPV-HN(I)
      Se3 S10, and the deduced amino acid sequences of the polyhedrin proteins were
      identical. Segment S7, 1 501 nucleotides, encoded a protein of 448 amino acids (
      approximately 50 kDa; p50). Thirty-one nucleotide mutations were found between
      DpCPV-HN(I) S7 and DpCPV-HN(I)-Se3 S7, but these resulted in only four amino acid
      changes. DpCPV-HN(I) S6 encoded a protein of 561 amino acids (63,688 Da; p64).
      The amino acid sequence of p64, had a high leucine content (10%), and contained a
      leucine zipper motif and one ATP/GTP-binding site motif.

PMID- 14689284
TI  - A naturally occurring recombinant isolate of Lettuce mosaic virus.
AB  - LMV-Common and LMV-Most are two seed-borne types of Lettuce mosaic virus (LMV),
      genus Potyvirus. LMV-Most, but not LMV-Common, overcomes the resistance afforded
      to lettuce by two recessive genes, mo11 and mo12. An RT-PCR-based assay thought
      to be specific for LMV-Most also amplified LMV-Tn2, previously typified as LMV
      Common. The sequence of selected regions along the genome indicated that LMV-Tn2
      is a natural recombinant between LMV-Most and LMV-Common isolates, with a
      putative recombination site located within the P3 coding region. This is the
      first evidence of a naturally occurring LMV recombinant isolate.

PMID- 14689285
TI  - Association of matrix protein of respiratory syncytial virus with the host cell
      membrane of infected cells.
AB  - The matrix protein of paramyxoviruses plays an important role in virus assembly
      through its interactions with cell membrane, virus envelope and virus
      nucleocapsid. In the present study, we investigated the possible association of
      respiratory syncytial virus (RSV) matrix (M) protein with the plasma membrane of
      infected cells. Using confocal microscopy we found that M was present at the
      cytoplasmic side of the plasma membrane. We used flotation gradients to purify
      membranes from RSV infected cells and treated them with cold Triton X-100 to
      obtain lipid rafts in the insoluble fraction. Western blot of the lipid raft
      fraction with specific antibodies showed that it contained M, as well as G
      (attachment) and N (nucleocapsid) proteins. We also found that RSV purified on
      sucrose gradients contained lipid raft markers. Together, our data suggest that
      RSV uses lipid rafts for assembly and budding.

PMID- 14689286
TI  - Cauda equina syndrome due to an intra-dural sacral cyst in type-1 Gaucher
      disease.
AB  - The authors report a rare case of type-1 Gaucher disease with neurological and
      haematological involvement. The first onset was epilepsy, the diagnosis of GD1
      was then confirmed and the patient experienced parkinsonism. The biological
      analysis revealed monoclonal gammapathy and factor-II mutation. The patient's
      condition worsened due to cauda equina syndrome. Magnetic resonance imaging and
      surgery revealed an intra-thecal sacral cyst which, to our knowledge, has not
      been reported previously; therefore, when confronted with the fractures commonly
      observed in GD1, other unusual causes of spinal cord and root compression should
      not be overlooked.

PMID- 14689287
TI  - Extradural lumbosacral cavernous hemangioma.
AB  - Purely extradural cavernous hemangiomas of the spinal canal are extremely rare.
      Their occurrence at the lumbosacral level is a true exception. We describe a case
      of lumbosacral extradural hemangioma and review the behaviour and MR imaging
      characteristics of these lesions. Cavernous hemangioma should be considered in
      the differential diagnosis of an enhancing extradural periradicular mass causing
      chronic lumbar radiculopathy especially in fertile women. Lumbar extradural
      hemangiomas appear and behave differently, not only from intramedullary cavernous
      hemangiomas but also from extradural hemangiomas of other spinal locations.

PMID- 14689288
TI  - Mycorrhizal symbionts of Populus to be sequenced by the United States Department
      of Energy's Joint Genome Institute.

PMID- 14689289
TI  - Post-streptococcal acute glomerulonephritis in Chile--20 years of experience.
AB  - In order to characterize the epidemiological and clinical picture of post
      streptococcal acute glomerulonephritis (PSAGN), a prospective study was designed
      to investigate all admissions to a general hospital of a local health service in
      Chile. The protocol included the investigation of previous streptococcal
      infections (SI), clinical symptoms and signs, socioeconomic situation (SES),
      throat and skin swabs for the isolation of group A beta-hemolytic streptococci,
      sequential determination of serum antistreptolysin O (ASO) titer, anti-DNAase B
      antibodies, and C3. During the 20 years studied, 926 cases were admitted (56%
      males). Incidence showed an endemic period (EP) 1980-1983, an epidemic outbreak
      (EO) 1984-1989, and a late period (LP) 1990-1999, with a rate per 100,000
      inhabitants of 6.2, 13.2, and 1.7, respectively. The clinical picture was similar
      in the three periods. SES was homogeneous, with 80% of the population in low and
      middle-low categories. The average size of the family was 6.9 compared with 4.8
      in the general population. Pyoderma was more frequent than pharyngeal infection,
      and more so during the EO. The isolation rate of group A beta-hemolytic
      streptococci from the pharynx was 20% compared with 60% from skin swabs. During
      EP, the most prevalent serotypes were T14-M0 and T1-M1 from the pharynx and
      TImp19-M0 from the skin. During EO, T14-M0 was more prevalent (30%). M or T
      classification was possible in EP and EO in 80%-85% of all strains isolated from
      the two locations. Significant titers for ASO and anti-DNAase B were found on
      admission: 55% and 75%, respectively. Both tests allowed identification of 100%
      of previous SI. In conclusion, the incidence of PSAGN had an uneven trend during
      the observed period. EO was mainly due to skin infection and a predominance of
      one serotype, T14-MO, was observed. After the EO, the yearly rate gradually
      decreased from 13.2 in 1988 to 0.0 in 1999, a rate similar to that of
      industrialized nations.

PMID- 14689290
TI  - Videourodynamics in the diagnosis of urinary tract abnormalities in a single
      center.
AB  - The lower urinary tract is a complicated structure and there has been some
      controversy regarding the biomechanics and dynamics of bladder and sphincter
      function. Investigation of the function and morphological anomalies is very
      important. Videourodynamics (VUD) combined with conventional voiding
      cystourethrography (VCUG) seems to be the most appropriate method. Over a 12-year
      study period (January 1990 to December 2001), 422 children (aged 5 days to 20
      years) prospectively underwent VUD to further define their urinary tract
      abnormalities. In all children the history was recorded, clinical examination,
      urinalysis, culture, and ultrasonography performed, and serum creatinine
      determined before VUD. The selection criteria included a history of recurrent
      urinary tract infections (UTI) in 310 patients (74%), urinary tract dilatation
      without UTI in 31 patients (7%), suspected neurogenic bladder dysfunction in 42
      patients (10%), and voiding difficulties in 39 patients (9%). VUD consists of
      cystometry (CM), which is the measurement of detrusor pressure during controlled
      bladder filling and subsequent voiding, and was combined with VCUG using X-ray
      contrast material. CM is used to assess detrusor activity, sensation, capacity,
      and compliance. CM measurements were recorded on a computer and vesicoureteric
      reflux (VUR) was documented at the same time with plain films and later in a PACS
      system. The VUD diagnosis was of normal bladder function in 46 patients (9%), VUR
      in 212 (43%), unstable bladder dysfunction in 152 (31%), neurogenic bladder
      dysfunction in 35 (7%), urine outflow obstruction in 15 (3%), wide bladder neck
      in 22 (4%), and vaginal reflux in 9 (2%). Neurogenic bladder dysfunction was
      excluded in 7 patients (1%). VUD is useful for the investigation of the lower
      urinary tract function together with X-ray morphology. The advantage of these
      studies is that they combine the objectivity of urodynamics with the visual
      radiographic image, leading to lower radiation doses and a more logical
      interpretation of the results.

PMID- 14689291
TI  - Laparoscopic identification and removal of focal lesions in persistent
      hyperinsulinemic hypoglycemia of infancy.
AB  - BACKGROUND: Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a
      heterogeneous condition. A number of children have focal lesions, and removal of
      these lesions is curative. However, these lesions are difficult to detect, even
      during surgery. A laparoscopic approach is beneficial. METHODS: Two children with
      PHHI underwent laparoscopic pancreatic inspection at 32 and 29 days of age,
      respectively. RESULTS: In both children, a lesion was easily found in the head of
      the pancreas. The lesions looked more lobular, had a more pronounced blood
      supply, and appeared to have a firmer texture than the remaining pancreas.
      Enucleation was curative. CONCLUSION: A laparoscopic approach seems to be ideal
      for patients with PHHI not only because of the magnification but also because of
      the delicate surgery it allows and the avoidance of major abdominal wall
      problems.

PMID- 14689292
TI  - Response of desert biological soil crusts to alterations in precipitation
      frequency.
AB  - Biological soil crusts, a community of cyanobacteria, lichens, and mosses that
      live on the soil surface, occur in deserts throughout the world. They are a
      critical component of desert ecosystems, as they are important contributors to
      soil fertility and stability. Future climate scenarios predict alteration of the
      timing and amount of precipitation in desert environments. Because biological
      soil crust organisms are only metabolically active when wet, and as soil surfaces
      dry quickly in deserts during late spring, summer, and early fall, the amount and
      timing of precipitation is likely to have significant impacts on the
      physiological functioning of these communities. Using the three dominant soil
      crust types found in the western United States, we applied three levels of
      precipitation frequency (50% below-average, average, and 50% above-average) while
      maintaining average precipitation amount (therefore changing both timing and size
      of applied events). We measured the impact of these treatments on photosynthetic
      performance (as indicated by dark-adapted quantum yield and chlorophyll a
      concentrations), nitrogenase activity, and the ability of these organisms to
      maintain concentrations of radiation-protective pigments (scytonemin, beta
      carotene, echinenone, xanthophylls, and canthaxanthin). Increased precipitation
      frequency produced little response after 2.5 months exposure during spring (1
      April-15 June) or summer (15 June-31 August). In contrast, most of the above
      variables had a large, negative response after exposure to increased
      precipitation frequency for 6 months spring-fall (1 April-31 October) treatment.
      The crusts dominated by the soil lichen Collema, being dark and protruding above
      the surface, dried the most rapidly, followed by the dark surface cyanobacterial
      crusts (Nostoc- Scytonema- Microcoleus), and then by the light cyanobacterial
      crusts (Microcoleus). This order reflected the magnitude of the observed
      response: crusts dominated by the lichen Collema showed the largest decline in
      quantum yield, chlorophyll a, and protective pigments; crusts dominated by Nostoc
      Scytonema-Microcoleus showed an intermediate decline in these variables; and the
      crusts dominated by Microcoleus showed the least negative response. Most previous
      studies of crust response to radiation stress have been short-term laboratory
      studies, where organisms were watered and kept under moderate temperatures. Such
      conditions would give crust organisms access to ample carbon to respond to
      imposed stresses (e.g., production of UV-protective pigments, replacement of
      degraded chlorophyll). In contrast, our longer-term study showed that under field
      conditions of high air temperatures and frequent, small precipitation events,
      crust organisms appear unable to produce protective pigments in response to
      radiation stress, as they likely dried more quickly than when they received
      larger, less frequent events. Reduced activity time likely resulted in less
      carbon available to produce or repair chlorophyll a and/or protective pigments.
      Our findings may partially explain the global observation that soil lichen cover
      and richness declines as the frequency of summer rainfall increases.

PMID- 14689293
TI  - Bridging meta-analysis and the comparative method: a test of seed size effect on
      germination after frugivores' gut passage.
AB  - Most studies using meta-analysis try to establish relationships between traits
      across taxa from interspecific databases and, thus, the phylogenetic relatedness
      among these taxa should be taken into account to avoid pseudoreplication derived
      from common ancestry. This paper illustrates, with a representative example of
      the relationship between seed size and the effect of frugivore's gut on seed
      germination, that meta-analytic procedures can also be phylogenetically corrected
      by means of the comparative method. The conclusions obtained in the meta
      analytical and phylogenetical approaches are very different. The meta-analysis
      revealed that the positive effects that gut passage had on seed germination
      increased with seed size in the case of gut passage through birds whereas
      decreased in the case of gut passage through non-flying mammals. However, once
      the phylogenetic relatedness among plant species was taken into account, the
      effects of gut passage on seed germination did not depend on seed size and were
      similar between birds and non-flying mammals. Some methodological considerations
      are given to improve the bridge between the meta-analysis and the comparative
      method.

PMID- 14689294
TI  - Effects of forest fragmentation on male and female reproductive success in
      Cestrum parqui (Solanaceae).
AB  - In this paper we evaluate the effects of forest fragmentation on male (pollen
      removal, pollen load, and pollen tubes) and female reproductive success (fruit-
      and seed-set) of Cestrum parqui, a self-incompatible, pollination-specialist
      plant species. We also measure focal individual conspecific density to account
      for possible density-related effects that could influence the response variables.
      We calculate an index which incorporates male and female fitness and gives an
      integrated assessment of overall reproductive success. Forest fragmentation
      strongly affected the amount of pollen grains on stigmas and number of pollen
      tubes as well as seed-set, decreasing from continuous forest to small forest
      fragments, whereas focal individual conspecific density failed to explain any of
      the variability for the studied variables. Declines in overall reproductive
      success (i.e. male and female) in small forest fragments are ascribed to
      decreases in both the quality and quantity of pollination. Self-incompatibility
      coupled with a specialist pollination system may be particularly important traits
      determining the negative fragmentation effects observed in C. parqui. Logarithmic
      regression models described the behaviour of the variables along the
      fragmentation size gradient, allowing us to detect a threshold below which the
      effects of fragmentation begin to negatively affect reproductive success in C.
      parqui. Our results emphasize the importance of evaluating both components of the
      total plant fitness, as well as including simultaneously several aspects of
      pollination and reproduction processes when assessing the effects of forest
      fragmentation on plant reproductive success.

PMID- 14689295
TI  - Interspecific variation in the defensive responses of obligate plant-ants:
      experimental tests and consequences for herbivory.
AB  - The aggressive behavior of ants that protect plants from herbivores in exchange
      for rewards such as shelter or food is thought to be an important form of biotic
      defense against herbivory, particularly in tropical systems. To date, however, no
      one has compared the defensive responses of different ant taxa associated with
      the same plant species, and attempted to relate these differences to longer-term
      efficacy of ant defense. We used experimental cues associated with herbivory-
      physical damage and extracts of chemical volatiles from leaf tissue--to compare
      the aggressive responses of two ant species obligately associated with the
      Amazonian myrmecophyte Tococa bullifera (Melastomataceae). We also conducted a
      colony removal experiment to quantify the level of resistance from herbivores
      provided to plants by each ant species. Our experiments demonstrate that some
      cues eliciting a strong response from one ant species elicited no response by the
      other. For cues that do elicit responses, the magnitude of these responses can
      vary interspecifically. These patterns were consistent with the level of
      resistance provided from herbivores to plants. The colony removal experiment
      showed that both ant species defend plants from herbivores: however, herbivory
      was higher on plants colonized by the less aggressive ant species. Our results
      add to the growing body of literature indicating defensive ant responses are
      stimulated by cues associated with herbivory. However, they also suggest the
      local and regional variation in the composition of potential partner taxa could
      influence the ecology and evolution of defensive mutualisms in ways that have
      previously remained unexplored.

PMID- 14689296
TI  - Trophodynamic linkage between river runoff and coastal fishery yield elucidated
      by stable isotope data in the Gulf of Lions (NW Mediterranean).
AB  - The link between climate-driven river runoff and sole fishery yields observed in
      the Gulf of Lions (NW Mediterranean) was analysed using carbon- and nitrogen
      stable isotopes along the flatfish food webs. Off the Rhone River, the main
      terrestrial (river POM) and marine (seawater POM) sources of carbon differed in
      delta(13)C (-26.11 per thousand and -22.36 per thousand, respectively). Surface
      sediment and suspended POM in plume water exhibited low delta(13)C (-24.38 per
      thousand and -24.70 per thousand, respectively) that differed more from the
      seawater POM than from river POM, demonstrating the dominance of terrestrial
      material in those carbon pools. Benthic invertebrates showed a wide range in
      delta(15)N (mean 4.30 per thousand to 9.77 per thousand ) and delta(13)C (mean 
      23.81 per thousand to -18.47 per thousand ), suggesting different trophic levels,
      diets and organic sources. Among the macroinvertebrates, the surface (mean
      delta(13)C -23.71 per thousand ) and subsurface (mean delta(13)C -23.81 per
      thousand ) deposit-feeding polychaetes were particularly (13)C depleted,
      indicating that their carbon was mainly derived from terrestrial material. In
      flatfish, delta(15)N (mean 9.42 to 10.93 per thousand ) and delta(13)C (mean 
      19.95 per thousand to -17.69 per thousand ) varied among species, indicating
      differences in food source and terrestrial POM use. A significant negative
      correlation was observed between the percentage by weight of polychaetes in the
      diet and the delta(13)C of flatfish white muscle. Solea solea (the main
      polychaete feeder) had the lowest mean delta(13)C, Arnoglossus laterna and
      Buglossidium luteum (crustacean, mollusc and polychaete feeders) had intermediate
      values, and Solea impar (mollusc feeder) and Citharus linguatula (crustacean and
      fish feeder) exhibited the highest delta(13)C. Two different benthic food webs
      were thus identified off the Rhone River, one based on marine planktonic carbon
      and the other on the terrestrial POM carried by the river. Deposit-feeding
      polychaetes were responsible for the main transfer of terrestrial POM to upper
      trophic levels, linking sole population dynamics to river runoff fluctuations.

PMID- 14689297
TI  - Experimental evidence that terrestrial carbon subsidies increase CO2 flux from
      lake ecosystems.
AB  - Subsidies are donor-controlled inputs of nutrients and energy that can affect
      ecosystem-level processes in a recipient environment. Lake ecosystems receive
      large inputs of terrestrial carbon (C) in the form of dissolved organic matter
      (DOM). DOM inputs may energetically subsidize heterotrophic bacteria and
      determine whether lakes function as sources or sinks of atmospheric CO(2). I
      experimentally tested this hypothesis using a series of mesocosm experiments in
      New England lakes. In the first experiment, I observed that CO(2) flux increased
      by 160% 4 days following a 1,000 microM C addition in the form of DOM. However,
      this response was relatively short lived, as there was no effect of DOM
      enrichment on CO(2) flux beyond 8 days. In a second experiment, I demonstrated
      that peak CO(2) flux from mesocosms in two lakes increased linearly over a broad
      DOM gradient (slope for both lakes=0.02+/-0.001 mM CO(2).m(-2) day(-1) per microM
      DOC, mean+/-SE). Concomitant changes in bacterial productivity and dissolved
      oxygen strengthen the inference that increasing CO(2) flux resulted from the
      metabolism of DOM. I conducted two additional studies to test whether DOM
      correlated attributes were responsible for the observed change in plankton
      metabolism along the subsidy gradient. First, terrestrial DOM reduced light
      transmittance, but experimental shading revealed that this was not responsible
      for the observed patterns of CO(2) flux. Second, organically bound nitrogen (N)
      and phosphorus (P) accompanied DOM inputs, but experimental nutrient additions
      (without organic C) caused mesocosms to be saturated with CO(2). Together, these
      results suggest that C content of terrestrial DOM may be an important subsidy for
      freshwater bacteria that can influence whether recipient aquatic ecosystems are
      sources or sinks of atmospheric CO(2).

PMID- 14689298
TI  - Species-specific patterns of hydraulic lift in co-occurring adult trees and
      grasses in a sandhill community.
AB  - Plants can significantly affect ecosystem water balance by hydraulic
      redistribution (HR) from dry to wet soil layers via roots (also called hydraulic
      lift, HL, when the redistribution is from deep to shallow soil). However, the
      information on how co-occurring species in natural habitats differ in HL ability
      is insufficient. In a field study, we compared HL ability of four tree species
      (including three congeneric oak species) and two C4 bunch grass species that co
      occur in subxeric habitats of fall-line sandhills in southeastern USA. Soil water
      potentials (psi(s)) were recorded hourly for 3 years both in large chambers that
      isolated roots for each species and outside the chambers. Outside of root
      chambers, soil drying occurred periodically in the top 25 cm and corresponded
      with lack of precipitation during the summer growing season. Soil moisture was
      continuously available at a 1 m depth. HL activity was observed in three of the
      tree species, with greater frequency for Pinus palustris than for Quercus laevis
      and Q. incana. The fourth tree species Q. margaretta did not exhibit HL activity
      even though it experienced a similar psi(s) gradient. For the C4 bunch grasses,
      Aristida stricta exhibited a small amount of HL activity, but Schizachyrium
      scoparium did not. The capacity for HL activity may be linked to the species
      ecological distribution. The four species that exhibited HL activity in this
      subxeric habitat are also dominant in adjacent xeric sandhill habitats, whereas
      the species that did not exhibit HL are scarcely found in the xeric areas. This
      is consistent with other studies that found greater fine root survival in dry
      soil for the four xeric species exhibiting HL activity. The differential ability
      of these species to redistribute water from the deep soil to the rapidly drying
      shallow soil likely has a strong effect on the water balance of sandhill plant
      communities, and is likely linked to their differential distribution across
      edaphic gradients.

PMID- 14689299
TI  - Biomass allocation, growth, and photosynthesis of genotypes from native and
      introduced ranges of the tropical shrub Clidemia hirta.
AB  - We tested the hypothesis that the tropical shrub Clidemia hirta appears more
      shade tolerant and is more abundant in its introduced than native range because
      of genetic differences in resource acquisition, allocation, and phenotypic
      plasticity between native and introduced genotypes. We examined growth, biomass
      allocation, and photosynthetic parameters of C. hirta grown in a greenhouse from
      seed collected from four populations in part of its native range (Costa Rica) and
      four populations in part of its introduced range (Hawaiian Islands). Six-month
      old seedlings were placed in high (10.3-13.9 mol m(-2) day(-1)) or low (1.4-4.5
      mol m(-2) day(-1)) light treatments and grown for an additional 6 months. Our
      study provided little evidence that Hawaiian genotypes of C. hirta differed
      genetically from Costa Rican genotypes in ways that would contribute to
      differences in habitat distribution or abundance. Some of the genetic differences
      that were apparent, such as greater allocation to stems and leaf area relative to
      whole plant biomass in Costa Rican genotypes and greater allocation to roots in
      Hawaiian genotypes, were contrary to predictions that genotypes from the
      introduced range would allocate more biomass to growth and less to storage than
      those from the native range. Hawaiian and Costa Rican genotypes displayed no
      significant differences in relative growth rates, maximal photosynthetic rates,
      or specific leaf areas in either light treatment. In the high light environment,
      however, Hawaiian genotypes allocated more biomass to reproductive parts than
      Costa Rican genotypes. Phenotypic plasticity for only 1 of 12 morphological and
      photosynthetic variables was greater for Hawaiian than Costa Rican genotypes. We
      conclude that genetic shifts in resource use, resource allocation, or plasticity
      do not contribute to differences in habitat distribution and abundance between
      the native and introduced ranges of C. hirta.

PMID- 14689300
TI  - Host-specific performance and host use in the kleptoparasitic marine snail
      Trichotropis cancellata.
AB  - Generalist parasites may disproportionately use certain hosts because of
      different benefits associated with each host species. I measured the growth rate
      of the marine snail Trichotropis cancellata, a facultative kleptoparasite that
      can suspension feed and steal food, on different hosts to determine the relative
      nutritional benefits of each host. The variation in tentacle (feeding structure)
      area among the hosts studied had the potential to provide parasitic snails with
      different amounts of nutrition for growth. In field experiments, suspension
      feeding snails isolated from potential hosts grew at a similar rate to snails on
      brachiopods and significantly more slowly than snails on the following polychaete
      worms: Serpula columbiana (Serpulidae), Pseudopotamilla ocellata (Sabellidae),
      Schizobranchia insignis (Sabellidae), and Eudistylia vancouveri (Sabellidae).
      However, choice among worm hosts affected snail growth rates only in the fall,
      when phytoplankton levels are low. At this time, snails parasitizing the
      sabellids Schizobranchia and Eudistylia grew more quickly than snails on Serpula.
      In the spring and summer, with high levels of phytoplankton, Trichotropis grew at
      similar rates on all worm species tested. Trichotropis spent approximately the
      same time stealing food from each worm host species, >50% of the time the worms
      had their tentacles extended (the difference among hosts was not significant).
      This finding demonstrates that the similarity of snail growth rates on different
      worm species is not due to the snails compensating for poor hosts (worms that
      provide food at a slower rate) by spending more time stealing food. Snails in
      choice experiments preferred live Serpula to empty Serpula tubes, indicating that
      at least some of the cue(s) snails use to identify hosts are derived from living
      host tissues. In choice racks containing live Serpula and live Schizobranchia,
      snails did not choose one host worm significantly more often than the other.
      Because Trichotropis grows faster on sabellids than serpulids in the fall, I
      predicted that snails in nature would infect sabellids more often than other
      species. However, snails were usually distributed randomly among host species. In
      the few cases where the snails showed a significant preference among host
      species, proportionally more snails were found on serpulids than on sabellids or
      sabellarids. This study is the first to quantify under natural conditions the
      growth benefits of a kleptoparasite across the range of possible hosts, and
      implies that factors other than growth rate influence host choice specificity in
      the marine kleptoparasite T. cancellata.

PMID- 14689301
TI  - Spatio-temporal patterns of soil available nutrients following experimental
      disturbance in a pine forest.
AB  - Although disturbance is known to alter soil nutrient heterogeneity, it remains
      unclear whether spatial patterns in soil nutrients after disturbance follow
      predictable temporal changes that reflect underlying processes. This study
      examined the effects of tree harvesting and girdling on overall variability,
      geostatistical patterns, and resource congruence of soil available nutrients in a
      mature Pinus elliottii Engelm. forest. The two disturbances led to different
      patterns of vegetation removal, forest floor redistribution, and revegetation,
      but showed similar post-disturbance changes in overall soil nutrient variability.
      Soil nutrient variability increased after both disturbances by more than 5-fold,
      and then decreased, returning to the undisturbed level in 4 years. Spatial
      structures assessed using geostatistics did not show predictable temporal trends.
      However, girdled plots showed more persistent spatial structures in soil
      nutrients than harvested plots, and had semivariogram ranges mostly equal to or
      less than 10 m, reflecting effects of persistent and spatially stable patches of
      undisturbed hardwoods that had an average patch size of 10 m. Resource congruence
      examined with Spearman rank correlations was nil before disturbance, increased
      after disturbance and then became nil again by the 4th year post-disturbance. The
      timing of the increase was related to treatment, occurring in the 1st year after
      disturbance in the girdled plots, but not until the 2nd year in the harvested
      plots. These two patterns of congruence were potentially caused by different
      rates of nutrient patch formation and resource uptake by plants during early
      succession. Although temporal changes in soil heterogeneity have been documented
      previously, the present study indicates that temporal trends in nutrient
      variability after disturbance may be predictable, and that the marked changes in
      spatio-temporal patterns of soil nutrients as a result of disturbance are
      ephemeral.

PMID- 14689303
TI  - PTEN immunohistochemical expression is suppressed in G1 endometrioid
      adenocarcinoma of the uterine corpus.
AB  - PURPOSE: PTEN is a tumor suppressor gene that inhibits cell proliferation by
      regulating intracellular signaling pathways, and this activity can be abolished
      by mutations of the PTEN gene. This study was designed to examine the correlation
      of PTEN expression with the expression of cell cycle regulators and with
      clinicopathological parameters in endometrioid adenocarcinoma of the uterine
      corpus. METHODS: Tissue samples of 117 endometrioid adenocarcinomas in addition
      to those of 19 normal endometria and 20 endometrial hyperplasias were used for
      the study. Immunohistochemical staining for PTEN protein was performed with the
      labeled streptavidin-biotin method on formalin-fixed and paraffin-embedded tissue
      samples. PTEN expression was represented as the staining score. RESULTS:
      Immunohistochemistry showed that the nuclei of cells were positive for PTEN. The
      PTEN staining score of normal endometrium was significantly higher in the
      proliferative phase than in the secretory phase. The scores of various
      endometrial hyperplasias were not significantly different from each other,
      regardless of the type of hyperplasia. The PTEN staining scores of endometrioid
      adenocarcinomas were 7.6+/-5.2 in G1, 9.6+/-5.2 in G2, and 11.9+/-3.7 in G3, and
      increased significantly as the histological grade increased. PTEN staining score
      was not significantly correlated with clinicopathological parameters such as FIGO
      stage, myometrial invasion, lymph-vascular space invasion (LVSI), lymph node
      metastasis or group, but was significantly correlated with labeling indices (LIs)
      of cell cycle regulators such as Ki-67, cdk2, cyclin A, cyclin D1, cyclin E, p27,
      and p53. The PTEN staining score of p53-wild cases was significantly lower than
      that of p53-mutant ones, but there was no significant difference of the score in
      cases with different PTEN gene status. PTEN expression was significantly lower in
      cases with both high levels of estrogen receptor and progesterone receptor.
      CONCLUSION: PTEN protein expression was decreased in well-differentiated and less
      growth-aggressive endometrial carcinoma with wild-type p53 gene and high levels
      of ER and PR. This suggests that disturbed PTEN expression occurs in an early
      phase of the tumorigenesis of well-differentiated endometrial carcinoma.

PMID- 14689304
TI  - Premature pubarche as an indicator of how body weight influences the onset of
      adrenarche.
AB  - Premature pubarche (PP) is defined as the development of pubic and/or axillary
      hair before the age of 8 years in girls and 9 years in boys. The objective was to
      obtain a clearer picture of the physiology of adrenarche by evaluating clinical
      laboratory features of PP. The 216 consecutive children were classified according
      to their sex and age of onset of PP: PP occurred before 2 years in 21 girls and
      one boy, between 4 and 7.9 years in 162 girls and between 5 and 8.9 years in 28
      boys. It occurred between 2 and 4 years in only four girls. The body mass index
      (BMI) was >/=+2 SD in 2 children aged <2 years (9.1%), in 52 girls aged >4 years
      (32.5%) and in 13 boys aged >5 years (46.4%). The plasma dehydroepiandrosterone
      sulphate (S-DHEA) concentrations in children aged <2 years were lower than those
      expected in Tanner stage 2. They were higher in obese girls >4 years than in lean
      ones ( P=0.009), with a positive correlation between S-DHEA and BMI z-score (
      P=0.004). Birth weights of girls >4 years were lower than those of the general
      population ( P<0.01). CONCLUSION: premature pubarche is rare in boys. The cause
      in children aged <2 years is probably different than in older ones. Premature
      pubarche is associated with low birth weight in girls. The frequency of obesity
      and the correlation between dehydroepiandrosterone sulphate levels and body mass
      index suggest that body weight is involved in the onset of adrenarche.

PMID- 14689302
TI  - A novel missense mutation in the paired domain of PAX9 causes non-syndromic
      oligodontia.
AB  - PAX9, a paired domain transcription factor, has important functions in
      craniofacial and limb development. Heterozygous mutations of PAX9, including
      deletion, nonsense, or frameshift mutations that lead to a premature stop codon,
      and missense mutations, were previously shown to be associated with autosomal
      dominant oligodontia. Here, we report a novel missense mutation that lies in the
      highly conserved paired domain of PAX9 and that is associated with non-syndromic
      oligodontia in one family. The mutation, 83G-->C, is predicted to result in the
      substitution of arginine by proline (R28P) in the N-terminal subdomain of PAX9
      paired domain. To rule out the possibility that this substitution is a rare
      polymorphism and to test whether the predicted amino acid substitution disrupts
      protein-DNA binding, we analyzed the binding of wild-type and mutant PAX9 paired
      domain to double-stranded DNA targets. The R28P mutation dramatically reduces DNA
      binding of the PAX9 paired domain and supports the hypothesis that loss of DNA
      binding is the pathogenic mechanism by which the mutation causes oligodontia.

PMID- 14689305
TI  - Idiopathic CD4+ T-lymphocytopenia in a boy with Down syndrome. Report of a
      patient and a review of the literature.

PMID- 14689307
TI  - Pseudomonas aeruginosa sepsis and ecthyma gangrenosum as initial manifestations
      of primary immunodeficiency.

PMID- 14689306
TI  - Electro-stimulation in preterm neonates with congenital auriculo-ventricular
      block. Report of three cases.
AB  - Congenital auriculo-ventricular blocks (CAVB) are usually linked to maternal auto
      immune diseases and their management remains controversial. We report three cases
      of CAVB in preterm newborns managed using electro-stimulation with an external,
      followed by an internal pacemaker. Results and long-term follow-up were
      satisfactory in all three children. CONCLUSION: the transitory placement of an
      external pacemaker seems necessary in low birth weight infants in order to allow
      weight gain and therefore the insertion of a permanent pacemaker. The prognosis
      seems good but a regular echocardiographic surveillance is of great importance in
      order to detect the onset of cardiac failure secondary to dilated cardiomyopathy.

PMID- 14689308
TI  - Frequent detection of parvovirus B19 genome in the myocardium of adult patients
      with idiopathic dilated cardiomyopathy.
AB  - Aside from enteroviruses and other viruses, e.g., adenoviruses, which are known
      to be associated with idiopathic dilated cardiomyopathy (IDC), a cardiac tropism
      is also attributed to parvovirus B19 (PVB19). The purpose of the present study
      was to determine the prevalence of enterovirus, adenovirus and PVB19 genomes in
      the myocardium of adult patients with IDC and to analyze the significance of
      PVB19 with regard to the course of the disease, as compared to the other
      cardiotropic viruses. In 52 adult patients with IDC and 10 control patients with
      normal left ventricular ejection fraction (> or =55%) undergoing coronary artery
      bypass surgery, myocardial tissue samples were investigated for enteroviral RNA
      using polymerase chain reaction (PCR) and Southern blot hybridization of the PCR
      product. Specific nested PCR was used to assess the prevalence of adenovirus and
      PVB19 DNA, in addition to sequencing of the latter. The clinical and
      echocardiographic course of the disease was followed for a mean (+/- SD) period
      of 21.1+/-9.5 months. Fourteen of the 52 patients (27%) were enterovirus
      positive, 2/52 (4%) patients were adenovirus-positive, 14/52 (27%) patients were
      PVB19-positive, 8/52 (15%) patients were enterovirus plus PVB19-positive, and in
      14/52 (27%) patients no viral genomes were found. Six patients died during the
      follow-up period, without any significant difference between the patient groups:
      1/14 (7%) in the enterovirus-positive, 0/2 (0%) in the adenovirus-positive, 2/14
      (14%) in the PVB19-positive, 1/8 (12.5%) in the enterovirus plus PVB19-positive,
      and 2/14 (14%) in the virus-negative group. PVB19 genome was found in 4 of the 10
      (40%) control patients, but no enterovirus or adenovirus genomes were detected in
      these patients. In conclusion, in the myocardium of patients with IDC, PVB19 is
      detectable as frequently as enteroviral genome. PVB19-positive patients with IDC
      have a rather favorable prognosis and do not differ significantly from the other
      virus-positive or virus-negative patient groups with respect to survival.
      Finally, the pathogenetic and prognostic significance of PVB19 in IDC still
      remains unclear.

PMID- 14689309
TI  - Indoor air quality and health problems associated with damp floor coverings.
AB  - OBJECTIVES: To study the relationship between a high incidence of bronchial
      asthma among employees working in an office building and an indoor air problem
      related to the degradation of polyvinyl chloride (PVC) floor coverings in the
      building. The indoor air measurements and results of renovations are also
      described. METHODS: Employees' symptoms were surveyed by a questionnaire, and the
      incidence of asthma was calculated from the medical records for 1997-2000. The
      quality of indoor air was assessed by microbial sampling and by investigation of
      the building for possible moisture damage. Indoor air was sampled for volatile
      organic compounds (VOCs) through Tenax adsorbent tubes. In situ volatile emission
      measurements from the concrete floor were performed via the field and laboratory
      emission cell (FLEC) method. RESULTS: In an office with approximately 150
      employees, eight new cases of asthma were found in 4 years. In addition, the
      workers complained of respiratory, conjunctival and nasal symptoms. Emissions
      indicating the degradation of plastic floor coverings (e.g. 2-ethyl-1-hexanol, 1
      butanol) were found in the indoor air and floor material samples. The plastic
      floor coverings, adhesives and the levelling layers were carefully removed from
      12 rooms. The VOCs had diffused into the underlying concrete slabs. The concrete
      was warmed to remove the diffused VOCs from these areas. After the repairs the
      concentrations of the VOCs indicating the degradation of PVC, decreased, as did
      the prevalence of the employees' symptoms and several asthma patients' need for
      medication. CONCLUSIONS: The workers in the office building complained of several
      respiratory, conjunctival and dermal symptoms. The incidence of adult-onset
      asthma was approximately nine-times higher than that among Finns employed in
      similar work. The most probable single cause of the indoor air problem was the
      degradation of the plastic floor coverings.

PMID- 14689310
TI  - Immunohistochemical localization of two otolith matrix proteins in the otolith
      and inner ear of the rainbow trout, Oncorhynchus mykiss: comparative aspects
      between the adult inner ear and embryonic otocysts.
AB  - The fish otolith consists mainly of calcium carbonate and organic matrices, the
      latter of which may play important roles in the process of otolith formation. We
      previously identified two otolith matrix proteins, named otolith matrix protein-1
      (OMP-1) and otolin-1, from the rainbow trout, Oncorhynchus mykiss, and the chum
      salmon, O. keta. In this study, recombinant proteins corresponding to OMP-1 and
      otolin-1 were synthesized using yeast and bacterial expression systems,
      respectively, to produce specific antibodies against each protein.
      Immunohistochemical analysis using these antisera revealed that in the otoliths
      of adult fish, OMP-1 and otolin-1 were colocalized along the daily rings possibly
      formed by alternate deposition of calcium carbonate and organic matrices. In the
      adult inner ear, OMP-1 was produced at most of the saccular epithelium, while
      otolin-1 was produced at a limited part of cylindrical cells located at the
      marginal zone of the sensory epithelium. In the embryonic inner ear, these
      proteins had already existed in the otolith primordia when calcification had
      commenced. In addition, otolin-1 was localized in the fibrous materials
      connecting otolith primordia and sensory epithelium at this stage. These results
      indicate that these proteins are required as essential components for otolith
      formation and calcification.

PMID- 14689311
TI  - Regional Symposium WFSBP "Joining forces for future challenges in Biological
      Psychiatry"11-13 December 2003, Bruges, Belgium. Abstracts.

PMID- 14689312
TI  - Effect of amalgam fillings on the mercury concentration in human amniotic fluid.
AB  - BACKGROUND: Methyl mercury (MeHg) and metallic Hg are well known as neurotoxic
      agents. Dental amalgam contributes significantly to elemental Hg vapour exposure
      in the general population. There is little information about Hg concentration in
      human amniotic fluid (AF) of pregnant women and its potential toxic effect on the
      fetuses. OBJECTIVE: Primary to assess the relationship between the presence of
      detectable mercury (Hg) concentration in human AF, number and surface areas of
      amalgam fillings of pregnant women; secondary to analyse their obstetric history
      and perinatal complications. METHODS: Seventy-two pregnant women took part in
      this prospective study. One dentist recorded the dental status, presence, number
      and surface areas of amalgam fillings. Total Hg concentration in AF was
      determined in digested samples using automatic cold vapour atomic absorption
      equipment. The detection limit of Hg in AF, determined from blank readings, was
      0.08 ng/ml. To estimate the dependence of the explanatory variables (such as
      number and surface areas of amalgam fillings, fish consumption, presence of liver
      or neurological diseases and smoking habits) on mercury concentration several
      linear regression models were built up. Stepwise logistic regression procedures
      were running on total sample and on patients with at least one amalgam filling
      (Positive Filling group = PF). Principal component analysis (PCA) provided two
      factors, which explained for more the 60% of the variance among the variables.
      RESULTS: The overall mean Hg concentration in AF among all patients was 0.37+/
      0.49 ng/ml. Nineteen (26.4%) women had a Hg concentration <0.08 ng/ml (Hg
      negative group). In 53 (73.6%) patients, with a concentration > or = 0.08 ng/ml
      (Hg positive group), the mean value of Hg was 0.49+/-0.52 ng/ml. The average
      number of amalgam fillings was 2.26 +/- 3.19 in the Hg negative group and 5.32+/
      3.03 in the Hg positive group (ANOVA one-way p=0.04). A dependence of mercury
      concentration on number of amalgam fillings (p=0.03), surface area of the amalgam
      fillings (p=0.04) and fish consumption (p=0.04) was observed but not at a
      significant level. In stepwise logistic procedure the number of amalgam fillings
      gave a contribution to the model (p=0.04), although null value was included in
      the confidence intervals. We observed no statistically significant differences
      (chi2 test) among the patients with a Hg concentration <0.08 ng/ml (n=19) and
      those with a concentration > or = 0.08 (n=53) with regard to obstetric history
      and perinatal complications. CONCLUSIONS: Number and surface areas of amalgam
      fillings influenced positively Hg concentration in AF but not at a significant
      level. Moreover Hg levels detected in AF were low and no adverse outcomes were
      observed through pregnancies and in the newborns.

PMID- 14689314
TI  - Urinary testosterone-metabolite levels and dominance rank in male and female
      bonobos (Pan paniscus).
AB  - The correlation between testosterone (T) and dominance rank may vary among
      species, and is expected to become stronger as the importance of aggressive
      competition for rank increases. However, it may also vary among social situations
      within a species, showing a stronger correlation during socially unstable
      periods. Knowledge on this topic in great apes, especially in females, is scant.
      This study presents the first data on the relationship between T and dominance
      rank in both sexes of the bonobo ( Pan paniscus). For each period (four socially
      unstable and two stable ones), linear rank orders were determined and
      subsequently correlated with the accompanying mean urinary T-metabolite
      concentrations (measured as immunoreactive 5alpha-androstan-17alpha-ol-3-one). No
      correlation between these two variables was found for either sex among
      individuals during socially unstable or stable periods. Also, within an
      individual over the six periods, no relationship of T with rank could be
      demonstrated. These results suggest that either the outcomes of aggressions have
      no influence on T levels, or such clear outcomes appear insufficiently frequent
      to affect T levels over longer periods. Even during the unstable periods, the
      rate of aggressions was not higher than during stable periods, suggesting that
      frequencies of aggression have little effect on rank. Further analyses indeed
      demonstrated no correlation between frequencies of overall aggressions or any
      type of aggressive behavior separately, or rank. Perhaps factors other than the
      frequency of displayed aggressions alone have a marked influence on a bonobo's
      rank, for example, coalition partners. Overall, in bonobos, T apparently does not
      form a physiological reflection of social status.

PMID- 14689315
TI  - Evaluation of Kluyveromyces marxianus FII 510700 grown on a lactose-based medium
      as a source of a natural bioemulsifier.
AB  - Mannoprotein with emulsification properties was extracted from the cell walls of
      Kluyveromyces marxianus grown on a lactose-based medium by autoclaving cells in a
      citrate buffer at pH 7. The purified product was evaluated for chemical and
      physical stability to establish its potential use as a natural emulsifier in
      processed foods. The yield of purified bioemulsifier from this strain of K.
      marxianus was 4-7% of the original dry cell weight. The purified product, at a
      concentration of 12 g l(-1), formed emulsions that were stable for 3 months when
      subjected to a range of pH (3-11) and NaCl concentrations (2-50 g l(-1)). The
      composition of this mannoprotein was 90% carbohydrate (mannan) and 4-6% protein.
      These values are similar to mannoprotein extracted from cells of Saccharomyces
      cerevisiae, which is the traditional source. Consequently K. marxianus cultivated
      on a low-cost lactose-based medium such as whey, a lactose-rich clean waste of
      the dairy industry, could be developed as a source of bioemulsifier for use in
      the food industry.

PMID- 14689316
TI  - Use of quantitative and semiquantitative procalcitonin measurements to identify
      children with sepsis and meningitis.

PMID- 14689317
TI  - Mycobacterium avium brain abscess at the initiation of highly active
      antiretroviral therapy.

PMID- 14689318
TI  - [Ancillary tests in uveitis].

PMID- 14689319
TI  - [Intravitreal administration of antiviral agents: repeated injections or
      implants?].

PMID- 14689320
TI  - [So many questions for such a few answers].

PMID- 14689321
TI  - [Retinal shortening: the most severe form of proliferative vitreoretinopathy
      (PVR)].
AB  - PURPOSE: To identify the clinical characteristics of patients developing retinal
      shortening due to intraretinal PVR. METHODS: Observational and retrospective
      cohort study on 110 PVR patients operated on between 2000 and 2001. During
      surgery, after removing epiretinal membranes and ruling out the presence of
      subretinal membranes, a perfluorocarbon liquid was injected. Those cases in which
      retinal flattening was not accomplished, were considered intraretinal PVR (group
      1). Those in which retinal flattening allowed endolaser application, were taken
      as the control group (group 2). Clinical features of both groups were compared by
      chi-square test. RESULTS: 60 cases (54.5%, CI 95%: 40.5-68.5) showed retinal
      shortening (group 1). In 24 cases (21.8%, CI 95%: 12.9-30.7) complete retinal
      flattening was accomplished (group 2). In 26 cases (23.6%), evaluation was
      inconclusive. In 9 out of the 60 cases of group 1 (15%) a retinectomy was
      necessary to reattach the retina. Differences between both groups were not
      statistically significant for any of the clinical variables. However, the number
      of retinal detachments of more than 60 days of evolution was significantly higher
      in retinectomized eyes (20.7%) than in group 1 (3.7%) (p=0.04). CONCLUSIONS:
      Retinal shortening is a relatively frequent phenomenon in PVR. Further studies
      are necessary to characterize this clinical presentation of PVR and its
      pathogenesis.

PMID- 14689322
TI  - [Subclinical keratoconus diagnosis by elevation topography].
AB  - PURPOSE: To evaluate the most effective parameters of Orbscan Corneal Topography
      System for subclinical keratoconus screening. METHODS: The study includes corneas
      from patients with clinical diagnosis of keratoconus (group 1, n=35), patients
      with subclinical keratoconus (group 2, n=14) and a control group of myopic
      subjects paired in gender, age and refractive spherical equivalent (group 3,
      n=35). Placement of the apex, anterior and posterior corneal elevation, minimal
      corneal thickness, anterior chamber depth and corneal diameter were evaluated.
      RESULTS: The most frequent location of the apex was at the inferotemporal sector
      (53%). Mean anterior elevation was 56.73 S.D. 25.95 mm in group 1 and 20.35 S.D.
      8.04 mm in group 2; results that are statistically significant different from the
      control group (p<0.001). Mean posterior elevation was 126.23 S.D. 57.7 mm in
      group 1 and 54.28 S.D. 19.55 mm in group 2, both showing a statistically
      significant difference from the control group (p<0.001). Minimal corneal
      thickness and anterior chamber depth also showed statistically significant
      differences between the three groups. No differences were found in corneal
      diameter values. CONCLUSIONS: Statistically significant differences were found in
      anterior and posterior elevation, minimal corneal thickness and anterior chamber
      depth parameters, as measured by the Orbscan system, between normal myopic
      subjects and those with clinical and sub-clinical keratoconus. These parameters
      should be considered in the detection of patients with increased risk for
      developing secondary keratectasia following corneal refractive surgery.

PMID- 14689323
TI  - [Comparative clinical study of visual results between two different types of
      bifocal intraocular lenses].
AB  - PURPOSE: To compare visual results after cataract surgery in patients who
      underwent bilateral implantation of two different types of bifocal intraocular
      lenses: the model 811E (Pharmacia), and the model MF4 (Ioltech). METHODS: This
      prospective study comprised 99 patients who underwent phacoemulsification with
      bifocal IOL implantation. The model 811E was implanted in forty-seven eyes of 47
      patients (group I) and the model MF4 in fifty-two eyes of 52 patients (group II).
      Visual acuity (distance and near), complications, and adverse events were
      measured. The postoperative follow-up in all patients was of 6 months. Patient
      satisfaction was also valued using a questionnaire. RESULTS: There was no
      significant difference in uncorrected distance visual acuity between both groups,
      which was respectively 0.63 (S.D.: 0.2) for group I and 0.58 (S.D.: 0.16) for
      group II (p=0.17). Nonetheless a significant difference was found when measuring
      corrected distance visual acuity, which was 0.86 (S.D.: 0.1) for group I and 0.77
      (S.D.: 0.12) for group II (p=0.01). Mean uncorrected near visual acuity was
      statistically better in group I: J2.00 (S.D.:1.16) in comparison with J2.48
      (S.D.:0.83) for group II (p=0.021). Subjectively, both groups indicated high
      levels of satisfaction, without significant difference between them, being
      respectively 78% (group I) and 73.4% (group II). CONCLUSIONS: Our results reveal
      a superiority of the bifocal diffractive lens over the refractive bifocal lens
      for corrected distance visual acuity and distance-corrected near visual acuity.
      Postoperatory complications and satisfaction degree were similar for both IOL
      models.

PMID- 14689324
TI  - [Indocyanine green angiography in chorioretinal inflammatory diseases].
AB  - PURPOSE: To determine the role of indocyanine green angiography (ICG) in handling
      chorioretinal inflammatory disorders. METHOD: We present several posterior
      uveitis whose diagnosis and therapeutic approach was facilitated with ICG.
      RESULTS: ICG is useful in the differential diagnosis of <<white-dot syndromes>>.
      In serpiginous choroiditis, the edges and the progression of the inflammatory
      areas are clearly delineated. In infectious uveitis such as toxoplasmosis, ICG
      determines the presence or absence of active lesions. There are granulomatous
      diseases such as sarcoidosis where some areas of choroidal inflammation that
      cannot be detected with other methods are shown by ICG. Moreover, ICG can detect
      areas of subretinal neovascularization in some choroidal pathologies such as
      polypoidal choroidal vasculopathy. CONCLUSIONS: ICG appears to be a useful and
      complementary tool in the clinical interpretation of posterior uveitis.

PMID- 14689325
TI  - [Fundus albipunctatus associated with cone dystrophy. A familial case report].
AB  - We report a familial case of fundus albipunctatus associated with cone dystrophy.
      CASE REPORT: Thirty-eight year-old male diagnosed with retinitis pigmentosa in
      another center. The main complain is a worsening of his night and color vision.
      Clinical and electrophysiological studies confirm the association of fundus
      albipuncatus with cone dystrophy. The family study found another cone dystrophy
      associated case in his thirty-three year-old affected brother. DISCUSSION: Though
      it is considerated a stationary disease, we report the association of fundus
      albipunctatus with symptoms and signs related to cone dysfunction. We review the
      possible nature of this association.

PMID- 14689326
TI  - [Saint Lucia in pictures].

PMID- 14689327
TI  - [Solana and the blindness].

PMID- 14689328
TI  - [Plans to reduce pain in the neonatal intensive care].
AB  - Prolonged pain influences behaviour and physiological regulation in preterm
      infants undergoing intensive care. Insufficient pain treatment results in
      increased morbidity and mortality. Long-term consequences of stress and pain yet
      are not clear, but associations with neurobehavioral and developmental sequelae
      are discussed. A number of psychometric constructs (pain scales) are available to
      identify pain indicators. These pain scales represent the basis to consider
      treatment strategies. Main indications are painful interventional procedures,
      analgesia during mechanical ventilation and the reduction of pain following
      surgery. Supporting approaches to reduce pain and stress relate to infant's
      behaviour, care of the professionals and improvement of "infant's world".
      Pharmacologic interventions are practicable with acetaminophen in mild pain and
      with opioid drugs (fentanyl and morphine) in moderate and severe pain. A pure or
      complementary sedative agent can provide physiological stability in settings in
      which there are less acutely painful stimuli. After standard pain evaluation it
      is necessary to individualize treatment, to monitor clinical situation and to
      adjust dosage. Actual knowledge allows an effective reduction of pain even in
      very premature infants. Because of lack of clarity about early development of
      pain and stress reactivity at the time it is necessary to estimate benefits
      against potential risks of therapy.

PMID- 14689329
TI  - [The clinical relevance of subcutaneous-thoracic ratio in preterm newborns as a
      possibility for quantification of capillary leak syndrome].
AB  - BACKGROUND: Capillary leak syndrome (CLS) is associated with increased morbidity
      and mortality in preterm newborns (PN) with sepsis or necrotizing enterocolitis.
      PATIENTS AND METHODS: In order to provide improved standards for measuring edema
      and for the definition of CLS, subcutaneous-thoracic ratios (S/T) were calculated
      from 821 anteroposterior supine chest radiographs of 119 PN with a birth weight
      below 1500 g. The S/T was computed by 100 % minus ratio of dividing the outer
      margins of the eighth rib by the total diameter of the thorax at the same
      position. Birth weight, gestational age, need for assisted ventilation and the
      position of the diaphragm did not significantly affect S/T. The S/T drifted
      downwards slightly with postnatal age. RESULTS: To provide normal standards of
      S/T in PN, the ratio was calculated in percentiles and the higher percentiles
      correlated with diseases. 771 S/T were lower than 10.1 % (95th percentile), 21
      were 10.1 - 12.6 % (97.5th percentile) and 20 were even higher. 3 of the 100 PN
      (84 %) with an S/T < 10.1 % died because of extreme immaturity. Eight patients
      (6.7 %) had an S/T between the 95th and the 97.5th percentile in at least one of
      their radiographs. Four of them had a respiratory distress syndrome and one died.
      Eleven PN had an S/T > 12.6 %. All of them showed a multiple organ failure and
      four died. When the SIT was > 15 % the edema became visible. A CLS was diagnosed
      in two PN with an S/T > 20 %. CONCLUSIONS: The threshold for the capillary leak
      syndrome was found to be 12.6 % also in reference to the course of diseases. The
      S/T is a useful tool because it is simple to measure and calculate, and is
      available from a single frontal film. The ratio can measure objectively the edema
      and the CLS in PN.

PMID- 14689330
TI  - [Osteonecrosis and HELLP-Syndrome].
AB  - BACKGROUND: In 25 % of patients who develope gestosis a Hemolysis- Elevated-
      Liver-enzymes-and- Low- Platelet-count-Syndrome (HELLP-Syndrome) may occur, which
      is characterized by activation of the coagulation mechanism and bone marrow
      alterations. Besides this therapeutical steroid application and an elevated age
      of primigravidity are responsible for an increased osteonecrosis risk in women,
      too. Because of anatomical and biomechanical reasons the highest incidence of
      pregnancy-associated osteonecrosis are the subchondral areas of the femoral
      epiphysial head. PATIENTS/METHODS: In this investigation data of pathogenesis,
      diagnostic work up and therapy in HELLP-associated osteonecrosis are reviewed and
      discussed based on a case report. We report of a 37-year old HELLP-patient
      showing bilateral femoral head osteonecrosis, who sustained a proximal femur
      fracture after bone marrow core decompression surgery. RESULTS/CONCLUSIONS: In
      pregnant patients with joint or bone associated pain an early MRI screening is
      recommended to detect osteonecrosis at early stages. This allows for therapeutic
      procedures which may be successful at early stages. If steroids are applicated
      for HELLP-treatment, the risk of osteonecrosis is elevated. DISCUSSION: Only
      early stages of osteonecrosis can be treated curatively. Sometimes it can be
      difficult to differentiate between early osteonecrosis stages, a bone marrow
      edema syndrome and a transient osteoporosis.

PMID- 14689331
TI  - [Prenatal diagnosis of obstructive uropathies - positive predictive value and
      effect on postnatal therapy].
AB  - INTRODUCTION: Prenatal diagnosis of urological anomalies is a standard procedure
      nowadays. The aim of this study was first to define the frequency of urinary
      tract anomalies in the selected patients in a level III center for prenatal
      diagnostics and therapy. The second aim was to show the accuracy of prenatal
      diagnosis in the special groups of obstructive uropathies. PATIENTS AND METHODS:
      Postnatal diagnoses were used for control of the prenatal findings. In the 12
      year retrospective study, we analyzed 21 616 pregnancies scanned for fetal
      anomalies. In 1 574 fetuses pediatric surgical anomalies were diagnosed. Out of 1
      077 follow-ups 618 patients with urinary tract anomalies were found. RESULTS: It
      could be shown that prenatal ultrasound has a high sensitivity for the diagnosis
      of obstructive renal tract anomalies. The diagnosis of subpelvine obstruction and
      muticystic kidney dysplasia can be made with an accuracy of 97 and 98 %. The
      therapeutic relevance of the diagnosis "isolated hydronephrosis" increases up to
      60 % when mild dilatation is neglected. False negative scans for urinary tract
      anomalies are low at 10 %. CONCLUSION: Hence, prenatal ultrasound for urinary
      tract anomalies is a method of high sensitivity. The therapeutic relevance is
      rather high. The most important question is to find all those patients who need a
      postnatal therapeutic approach immediately.

PMID- 14689332
TI  - [Music therapy for prematures].
AB  - BACKGROUND: More than ever before the neonatal care besides the medical and
      nursing work has to been balanced between protecting the child against over
      extension due to the concept of "minimal handling" and on the other hand the
      necessary fostering of the young patients psychic and sensomotor development
      during the long stationary treatment. In addition to known approaches of auditive
      stimulation as receptive music therapy a concept of active music therapy methods
      based on the Nordoff/Robbins creative music-therapy (University Witten/Herdecke)
      is presented in a case-report. PATIENT AND METHODS: The report describes in a
      single case-report the music-therapeutic work with a premature of the 23 + 3 (th)
      week of pregnancy at the neonatological unit of the Vestische Kinder- und
      Jugendklinik Datteln, Universitat Witten/Herdecke. The main focus was the
      observation of the prematures reactions on specific synchronisation of motoric,
      sensor and acoustical stimulation. RESULTS: Positive reactions allow to presume
      the effectiveness of music therapy with early born children as they are already
      shown in clinical studies about receptive music therapy. On the level of
      involuntary motional actions in the area of head-, face- and hand movements
      increased directly reactions of awareness on the coordination of sensomotor and
      acoustical stimulation have been observed. Temporary increase of oxygen partial
      pressure and reduction of heart/pulse rate seem to cause positive physiological
      effects. CONCLUSIONS: Active music therapeutic treatment does not seem to be an
      other risk of over-tension for prematures, but offers through the coordination of
      different levels of perception an adequate development fostering stimulation.

PMID- 14689333
TI  - [Reversible loss of vision in severe preeclampsia: case report and review of the
      literature].
AB  - Visual disturbances occur in up to 25 % of the patients with preeclampsia.
      However, blindness remains a rare phenomenon. A 39 year old primigravida was
      admitted for observation at 30 weeks gestation with signs of preeclampsia. After
      11 days she suffered a complete loss of vision. The blindness reversed completely
      after cesarean section and antihypertensive treatment. Blindness in preeclamptic
      patients is mostly caused by hypertensive encephalopathy. We discuss
      pathophysiological aspects as well as diagnostic approaches and therapeutic
      options with respect to the available literature.

PMID- 14689334
TI  - [Paroxetine withdrawal syndrome as differential diagnosis of acute neonatal
      encephalopathy?].
AB  - Paroxetine, a selective serotonin reuptake inhibitor (SSRI) may be given in
      severe cases of maternal depression and panic disorders during pregnancy.
      However, it may lead to severe withdrawal symptoms: respiratory distress,
      jitteriness, convulsions, hypoglycaemia, an impaired muscle tone and necrotising
      enterocolitis. These symptoms, also called neonatal withdrawal syndrome, may last
      up to one month. We report a girl born at 37 weeks of gestation presenting 12
      hours after birth with hypopnea, bradycardia and a decreased muscular tone of
      unknown origin. The child was transferred to the NICU and was intubated and
      ventilated mechanically. Within the first days the patient also developed
      cerebral seizures. The EEG showed severe abnormalities. Later we learned that the
      patient's mother had been treated with Paroxetine during pregnancy. The patient
      recovered after two days of ventilation and anticonvulsive medication with
      phenobarbital. The EEG result showed a siginificant improvement. At day 10 she
      was discharged in good condition. Recognition and treatment of the presented
      neonatal problems could have been more effective and faster, if the attending
      pediatricians had been informed earlier about the maternal medication with SSRIs.
      Neonates of mothers who were treated with SSRIs during pregnancy should be
      monitored. Paroxetine withdrawal syndrome should be considered as one of the
      differential diagnosis of neonatal encephalopathy.

PMID- 14689335
TI  - A multistate outbreak of Salmonella enterica Serotype Newport infection linked to
      mango consumption: impact of water-dip disinfestation technology.
AB  - Fresh produce increasingly is recognized as an important source of salmonellosis
      in the United States. In December 1999, the Centers for Disease Control and
      Prevention detected a nationwide increase in Salmonella serotype Newport (SN)
      infections that had occurred during the previous month. SN isolates recovered
      from patients in this cluster had indistinguishable pulsed-field gel
      electrophoresis (PFGE) patterns (which identified the outbreak strain),
      suggesting a common source. Seventy-eight patients from 13 states were infected
      with the outbreak strain. Fifteen patients were hospitalized; 2 died. Among 28
      patients enrolled in the matched case-control study, 14 (50%) reported they ate
      mangoes in the 5 days before illness onset, compared with 4 (10%) of the control
      subjects during the same period (matched odds ratio, 21.6; 95% confidence
      interval, 3.53- infinity; P=.0001). Traceback of the implicated mangoes led to a
      single Brazilian farm, where we identified hot water treatment as a possible
      point of contamination; this is a relatively new process to prevent importation
      of an agricultural pest, the Mediterranean fruit fly. This is the first reported
      outbreak of salmonellosis implicating mangoes. PFGE was critical to the timely
      recognition of this nationwide outbreak. This outbreak highlights the potential
      global health impact of foodborne diseases and newly implemented food processes.

PMID- 14689336
TI  - Salmonella in imported mangos: shoeleather and contemporary epidemiologic
      techniques together meet the challenge.

PMID- 14689337
TI  - High incidence of Haemophilus influenzae type b infection in children in Pacific
      island countries.
AB  - The Haemophilus influenzae type b (Hib) disease burden among children <5 years
      old in 4 Pacific island countries (PICs) was estimated. The incidence of
      confirmed Hib meningitis was calculated using the numbers of culture-confirmed
      isolates. In addition, the World Health Organization (WHO) Hib Rapid Assessment
      Tool (RAT) was used to estimate the true Hib meningitis incidence and the number
      of Hib meningitis and pneumonia cases, as well as the number of deaths due to Hib
      meningitis and pneumonia. The Hib meningitis annual incidence in 3 PICs was 70-84
      cases per 100,000 children <5 years old. For PICs, the RAT is likely to
      overestimate the Hib pneumonia burden, as it assumes a 5 : 1 ratio of Hib
      pneumonia to Hib meningitis. The true ratio is likely to be 1 : 1. The high Hib
      disease burden and the relative cost-effectiveness of Hib vaccine make the
      introduction of Hib vaccine a good investment for PICs, costing US1000 dollars
      US10,000 dollars for each death prevented--a number that ignores savings from
      reductions in the cost of treatment.

PMID- 14689338
TI  - Toward global Haemophilus influenzae type b immunization.

PMID- 14689339
TI  - Cytomegalovirus infection in immunocompetent patients.
AB  - Symptoms associated with cytomegalovirus (CMV) infection in immunocompetent
      patients are not well documented. From December 1998 through June 2001, serum
      samples obtained from 7630 patients in Cambridge and Chelmsford, United Kingdom,
      were tested for CMV immunoglobulin M. CMV immunoglobulin G avidity was used to
      confirm CMV infection. A total of 124 patients (106 patients treated by general
      practitioners [GPs] and 18 hospitalized patients) with CMV infection were
      identified. The most frequent symptoms were malaise (67%), fever (46%), and
      sweats (46%), and the most frequent finding was abnormal liver function test
      results (69%). Twelve percent of patients had a relapsing illness, and many had
      symptoms that lasted for up to 32 weeks (mean duration of symptoms, 7.8 weeks).
      GPs reported that there was a significant benefit in making the diagnosis of CMV
      infection; it provided reassurance and avoided the need for further
      investigations. We have identified symptoms associated with CMV infection in
      immunocompetent patients who present to GPs or who are admitted to the hospital.

PMID- 14689340
TI  - Look and ye shall find...cytomegalovirus infection in immunocompetent patients.

PMID- 14689341
TI  - Linezolid does not increase the risk of thrombocytopenia in patients with
      nosocomial pneumonia: comparative analysis of linezolid and vancomycin use.
AB  - Reports from uncontrolled studies suggest that linezolid is associated with rates
      of thrombocytopenia higher than those reported in clinical studies. We assessed
      the risk of thrombocytopenia in 686 patients with nosocomial pneumonia who
      received linezolid or vancomycin for > or =5 days in 2 randomized, double-blind
      studies and for whom follow-up platelet counts had been measured. New-onset
      thrombocytopenia (platelet count of <150x10(9) platelets/L) occurred in 19 (6.4%)
      of 295 linezolid recipients and 22 (7.7%) of 285 vancomycin recipients with
      baseline platelet counts of > or =150x10(9) platelets/L; severe thrombocytopenia
      (platelet count of <50x10(9) platelets/L) occurred in only 1 patient in each
      group. Platelet counts decreased to less than the baseline level in 4 (6.6%) of
      61 linezolid recipients and 5 (11.1%) of 45 vancomycin recipients who had
      baseline counts of <150x10(9) platelets/L. No patient had a decrease to <20x10(9)
      platelets/L. There were no statistically significant differences between groups
      in these or any other platelet assessments. Clinically significant
      thrombocytopenia was uncommon in our analysis, and linezolid was not associated
      with a greater risk of thrombocytopenia in seriously ill patients than was
      vancomycin.

PMID- 14689342
TI  - Assessment of mortality after long-term follow-up of patients with community
      acquired pneumonia.
AB  - Although studies have assessed short-term mortality among patients with community
      acquired pneumonia, there is limited data on prognosis and risk factors that
      affect long-term mortality. The mortality among patients enrolled at 4 sites of
      the Pneumonia Patient Outcome Research Team cohort study who survived at least 90
      days after presentation to the hospital was compared with that among age-matched
      control subjects. Overall, 1419 of 1555 patients survived for >90 days, with a
      mean follow-up period of 5.9 years. There was significantly higher long-term
      mortality among patients with pneumonia than among age-matched controls. Factors
      significantly associated with long-term mortality were age (stratified by
      decade), do-not-resuscitate status, poor nutritional status, pleural effusion,
      glucocorticoid use, nursing home residence, high school graduation level or less,
      male sex, preexisting comorbid illnesses, and the lack of feverishness. This
      study demonstrates that there is significantly higher long-term mortality among
      patients with pneumonia than among age-matched controls and that long-term
      mortality largely is not affected by acute physiologic derangements.

PMID- 14689343
TI  - Increased long-term mortality after an episode of community-acquired pneumonia-
      time to move beyond descriptive studies.

PMID- 14689344
TI  - Mupirocin prophylaxis to prevent Staphylococcus aureus infection in patients
      undergoing dialysis: a meta-analysis.
AB  - A systematic review of the English-language literature was performed to determine
      the overall benefit of mupirocin therapy in reducing the rate of Staphylococcus
      aureus infection among patients undergoing hemodialysis (HD) or peritoneal
      dialysis (PD). Included studies met the following criteria: they were randomized
      clinical trials or cohort studies; cohorts consisted of adults (age, > or =18
      years) requiring HD or PD; mupirocin therapy was administered to the treatment
      group, and placebo or no therapy was administered to the control group; and the
      primary outcome of interest was the difference in the number of S. aureus
      infections among mupirocin-treated and -untreated patients. Ten studies described
      in 9 articles were analyzed. A total of 2445 patients were included in the
      analysis. Use of mupirocin reduced the rate of S. aureus infections by 68% (95%
      confidence interval [CI], 57%-76%) among all patients undergoing dialysis; risk
      reductions were 80% (95% CI, 65%-89%) among patients undergoing HD and 63% (95%
      CI, 50%-73%) among patients undergoing PD. When data were stratified by type of
      infection, S. aureus bacteremia was found to be reduced by 78% among patients
      undergoing HD, and peritonitis and exit-site infections were found to be reduced
      by 66% and 62%, respectively, among patients undergoing PD. Mupirocin prophylaxis
      substantially reduces the rate of S. aureus infection in the dialysis population.
      Optimal regimens that minimize the emergence of mupirocin resistance need to be
      explored.

PMID- 14689345
TI  - The role of particular strains of Neisseria meningitidis in meningococcal
      arthritis, pericarditis, and pneumonia.
AB  - The clinical presentations of meningococcal diseases other than meningitis or
      meningococcemia may lead to erroneous diagnosis. Although several reports have
      described unusual meningococcal diseases, the Neisseria meningitidis strains
      involved in these forms have been poorly characterized. In this study,
      meningococcal arthritis and pericarditis were confirmed by isolation of N.
      meningitidis and/or detection of meningococcal DNA in synovial or pericardial
      fluid, respectively, and meningococcal pneumonia was detected by isolation of N.
      meningitidis from blood. From 1999 through 2002, meningococcal disease was
      bacteriologically confirmed in 26 cases of arthritis, 6 cases of pericarditis,
      and 33 cases of pneumonia by the National Reference Center for the Meningococci
      in Paris. We found a statistically significant association between strains of
      serogroup W135, mostly of the clonal complex ET-37, and arthritis. Pneumonia was
      most frequently diagnosed in patients aged >70 years, and 54.5% of the strains
      belonged to serogroup W135, although these strains had heterogeneous phenotypes.
      Bacteremia is a key step in the pathophysiology of meningococcal disease and
      precedes any form of invasive infection.

PMID- 14689346
TI  - Relationship between fluoroquinolone use and changes in susceptibility to
      fluoroquinolones of selected pathogens in 10 United States teaching hospitals,
      1991-2000.
AB  - We retrospectively examined the relationship between fluoroquinolone use and the
      susceptibilities of 11 bacterial pathogens to fluoroquinolones in 10 US teaching
      hospitals from 1991 through 2000. Statistical significance was determined by 2
      way analysis of variance, with the number of isolates tested each year as a
      weighting factor. The analysis of baseline-to-end point change in the percentage
      of susceptibility and the slope of the regression line (trend line) for logit
      percentage of susceptibility showed that the overall percentage of susceptibility
      to fluoroquinolones decreased significantly during the study period (P<.05) and
      that change in percentage of susceptibility was significantly related to change
      in fluoroquinolone use (P<.05). Particularly notable were the decreases in the
      susceptibilities of Pseudomonas aeruginosa, Proteus mirabilis, and Escherichia
      coli (decreases of 25.1%, 11.9%, and 6.8%, respectively).

PMID- 14689347
TI  - Comparison of bronchoscopy and gastric washings in the investigation of smear
      negative pulmonary tuberculosis.
AB  - This study compares the utility of gastric washings (GWs) and bronchoscopy in the
      diagnosis of smear-negative pulmonary tuberculosis (TB). The aim of the study was
      to identify which investigation or combination of investigations provided the
      greatest yield of positive Mycobacterium tuberculosis cultures of samples from
      patients with smear-negative pulmonary TB. We retrospectively analyzed the
      medical records of 180 patients with smear-negative pulmonary TB. The positive
      culture yield for bronchoalveolar lavage fluid (62 [34%] of 180 patients) was
      significantly greater than that for specimens from 3 GWs (32 [21%] of 149
      patients) (P=.02). Combining GW and bronchoscopy increased the positive culture
      yield: bronchoscopy combined with 2 GWs resulted in a positive culture rate of
      38%. Bronchoscopy is superior to GW in the diagnosis of smear-negative pulmonary
      TB; however, the combination of bronchoscopy and 2 GWs should be regarded as
      optimal for the diagnosis of smear-negative pulmonary TB.

PMID- 14689348
TI  - Plasma concentrations of tafenoquine, a new long-acting antimalarial agent, in
      thai soldiers receiving monthly prophylaxis.
AB  - We measured plasma tafenoquine concentrations in Thai soldiers given a monthly
      regimen of tafenoquine to determine whether these concentrations adequately
      suppressed malarial infections on the Thai-Cambodian border. After receiving a
      treatment course of artesunate and doxycycline, 104 male soldiers were
      administered a loading dose of tafenoquine (400 mg daily for 3 days), followed by
      tafenoquine monthly (400 mg every 4 weeks) for 5 months. Consecutive monthly mean
      (+/- standard deviation) trough plasma tafenoquine concentrations were 223+/-41,
      127+/-29, 157+/-51, 120+/-24, and 88+/-20 ng/mL. Only 1 soldier developed malaria
      during the study. At the time of malaria diagnosis, his plasma tafenoquine
      concentration was 40 ng/mL, which was approximately 3-fold lower than the trough
      concentrations of the other soldiers. Although low tafenoquine concentrations
      appear to be uncommon, additional investigations are needed to determine the
      relationship between plasma tafenoquine concentrations and suppression of
      malaria.

PMID- 14689349
TI  - Primaquine for prevention of malaria in travelers.
AB  - An expanding risk and range of endemic malaria threatens travelers. Primaquine is
      an old drug recently demonstrated to offer effective prophylaxis. Clinical trials
      conducted in Indonesia, Kenya, and Colombia showed that a primaquine base (30 mg
      per day) had protective efficacy against Plasmodium falciparum and Plasmodium
      vivax of 85%-93%. Among 339 children (age, >8 years) and adults taking this
      regimen for 12-52 weeks, there was no greater risk of adverse symptomatic events
      among primaquine users than among recipients of placebo in double-blind studies.
      Among 151 subjects evaluated after 20 or 52 weeks of daily primaquine therapy,
      methemoglobinemia was found to be mild (<13%; typically <6%) and transient
      (duration, <2 weeks). We consider primaquine base (0.5 mg/kg per day consumed
      with food) to be safe, well-tolerated, and effective prophylaxis against malaria
      for nonpregnant persons and those with normal glucose-6-phosphate dehydrogenase
      levels. Primaquine's major advantage over most drugs for chemoprophylaxis is that
      it does not have to be taken before entering or beyond 3 days after leaving a
      malarious area.

PMID- 14689350
TI  - Progress in the development of respiratory syncytial virus and parainfluenza
      virus vaccines.
AB  - Respiratory syncytial virus (RSV) and human parainfluenza viruses (hPIVs) are
      leading causes of viral lower respiratory tract illness in children and in high
      risk adult populations. Despite decades of research, licensed vaccines for RSV
      and hPIVs do not exist. Recently, however, genetically engineered live attenuated
      RSV and hPIV candidate vaccines have been generated, several of which are already
      being evaluated in clinical trials. Recombinant technology allows candidate
      vaccines to be "fine-tuned" in response to clinical data, which should hasten the
      development of vaccines against these important respiratory pathogens.

PMID- 14689351
TI  - Treatment of chronic hepatitis B in the human immunodeficiency virus-infected
      patient: present and future.
AB  - The management of chronic hepatitis B poses specific problems in the presence of
      human immunodeficiency virus (HIV) coinfection, because therapeutic approaches
      have to address both hepatitis B virus (HBV) and HIV infections. Response to
      interferon (IFN-alpha) is lower in HBV-HIV-coinfected than in HIV-negative
      subjects, especially in patients in advanced stages of immunosuppression. Thus
      far, there are no data on the performance of the new pegylated forms of IFN-alpha
      in HBV- and HIV-coinfected persons. After prolonged use of lamivudine, resistance
      develops in the majority of HBV-HIV-coinfected patients treated with the drug.
      The more recently approved tenofovir has shown excellent short-term results, and
      data from longer follow-up studies are eagerly awaited. Several drugs with
      combined anti-HIV and anti-HBV activity have recently been approved
      (emtricitabine) or are currently under development. Preliminary results with some
      of them are quite promising and probably will widen the therapeutic armamentarium
      against hepatitis B in patients with HIV infection.

PMID- 14689352
TI  - Effectiveness of isoniazid treatment for latent tuberculosis infection among
      human immunodeficiency virus (HIV)-infected and HIV-uninfected injection drug
      users in methadone programs.
AB  - Injection drug users (IDUs) were heavily affected by the tuberculosis (TB)
      resurgence in New York City in the 1990s. We assessed the effectiveness of
      screening for latent TB infection in methadone users and of selective treatment
      with isoniazid. Risk for future TB was classified as low or high on the basis of
      tuberculin, anergy, and HIV test results. The cohort of 2212 IDUs was followed up
      for a median of 4.2 years; 25 IDUs, of whom 20 (80%) were infected with human
      immunodeficiency virus (HIV), developed TB. In an adjusted Cox proportional
      hazards model of high-risk IDUs, the risk of TB was associated with HIV infection
      (HR 10.3; 95% CI, 3.4-31.3); receipt of <6 months of isoniazid therapy (HR 7.6;
      95% CI, 1.02-57.1); a CD4+ T lymphocyte count of <200 cells/mm3 (HR 6.6; 95% CI,
      1.7-25.9); and tuberculin positivity (HR 4.0; 95% CI, 1.6-10.2). Treatment with
      isoniazid was beneficial in HIV-infected, tuberculin-positive IDUs.

PMID- 14689353
TI  - Progressive reversion of human immunodeficiency virus type 1 resistance mutations
      in vivo after transmission of a multiply drug-resistant virus.
AB  - Evolution and transmission of multiply drug-resistant human immunodeficiency
      virus type 1 (HIV-1) may limit therapeutic options as global treatment efforts
      expand. However, the stability of these mutants in the absence of drug selection
      pressure is not known. We performed a longitudinal analysis of plasma virus from
      a person who acquired HIV-1 that contained multiple reverse transcriptase (RT)
      and protease (PR) mutations. In the absence of therapy, 5 of 12 drug resistance
      mutations reverted in a stepwise fashion to wild type over the course of 52
      weeks. Reversion of the M184V mutation alone did not change viral replicative
      capacity (RC), but it led to enhanced resistance to zidovudine and tenofovir.
      However, reversions of a second RT mutation and 3 PR mutations were associated
      with an increase in viral RC, and this was temporally correlated with a marked
      decrease in CD4 cell number. This study demonstrates the gradual stepwise back
      mutation of certain drug resistance mutations in vivo in the absence of ongoing
      drug selection pressure. Moreover, it suggests that, despite initially impaired
      viral fitness, a transmitted HIV-1 isolate with multiple drug resistance
      mutations can evolve to develop increased RC and significant pathogenicity.

PMID- 14689355
TI  - Human metapneumovirus-associated lower respiratory tract infections among
      hospitalized human immunodeficiency virus type 1 (HIV-1)-infected and HIV-1
      uninfected African infants.
AB  - Respiratory tract infections due to human metapneumovirus (hMPV) have been
      reported worldwide, with the exception of Africa. The prevalence of hMPV
      infection was studied among human immunodeficiency virus type 1 (HIV-1)-infected
      and HIV-1-uninfected African infants who were hospitalized for lower respiratory
      tract infections (LRTIs). Nasopharyngeal aspirate samples obtained from 81 HIV-1
      infected and 110 HIV-1-uninfected infants who had tested negative for other
      respiratory viruses were selected for investigation. hMPV was detected in 10 HIV
      1-uninfected infants (9.1%) and 3 HIV-1-infected infants (3.7%). Compared with
      the entire cohort of HIV-1-uninfected infants, hMPV was 4.6-fold less common than
      respiratory syncytial virus, but it was 3.2-fold more common than influenza virus
      and 2.1-fold more common than parainfluenza virus types 1-3. Genotyping of 7 of
      14 isolates revealed the circulation of 2 major phylogenetic groups of the virus,
      which were similar to those described in North America and Europe.

PMID- 14689354
TI  - Acute human immunodeficiency virus infection in patients presenting to an urban
      urgent care center.
AB  - Acute infection with human immunodeficiency virus (HIV) is often accompanied by a
      flu-like illness, and early identification and treatment may help control the
      infection and prevent transmission. We enrolled patients who presented to an
      urban urgent care center with any symptoms of a viral illness and any recent
      potential risk for HIV infection, and we tested them for acute HIV infection
      using enzyme-linked immunosorbent and RNA assays. Of 499 patients enrolled over a
      1-year period, acute HIV infection was diagnosed in 5 (1.0%; 95% confidence
      interval [CI], 0.1%-1.9%), and chronic HIV infection was diagnosed in 6 (1.2%;
      95% CI, 0.2%-2.2%). There were no false-positive results of the RNA assay. No
      signs or symptoms reliably distinguished patients with acute HIV infection from
      those who were HIV uninfected. Given the importance of this diagnosis, testing
      for acute HIV infection using RNA and antibody assays should be offered to all
      patients in similar settings with viral symptoms and any risk factors for HIV
      infection.

PMID- 14689356
TI  - Oxidant stress is increased during treatment of human immunodeficiency virus
      infection.
AB  - Some diseases and environmental exposures, including those that are risk factors
      for atherosclerosis, are associated with increased oxidant stress. The objective
      of this cross-sectional, observational study was to determine whether oxidant
      stress is increased during human immunodeficiency virus type 1 (HIV-1) infection
      or its therapy. To quantify oxidant stress, plasma F2 isoprostane (F2-IsoP)
      concentrations were determined by gas chromatography/mass spectroscopy. A total
      of 120 subjects were enrolled during routine primary care visits. The median CD4+
      T cell count was 341 cells/mm3, the median HIV-1 RNA level was 3.4 log10
      copies/mL, and 74% of patients were receiving antiretroviral therapy. Plasma F2
      IsoP concentrations were 12-149 pg/mL (median, 31 pg/mL). In univariate analysis,
      higher F2-IsoP concentrations were associated with lower log10 plasma HIV-1 RNA
      levels (P=.009) and with efavirenz use (P=.02). Both factors remained associated
      with plasma F2-IsoP concentrations in multivariate analysis. Oxidant stress
      associated with therapeutic control of viral replication may have important
      implications for long-term complications of antiretroviral therapy.

PMID- 14689357
TI  - Infection with hepatitis C virus transmitted by accidental needlesticks.

PMID- 14689358
TI  - Rifampin and recurrence of tuberculosis among patients infected with HIV.

PMID- 14689361
TI  - Antiretroviral drug resistance testing: potential use following nosocomial
      exposure to HIV.

PMID- 14689362
TI  - Safety and efficacy evaluation of pleconaril for treatment of the common cold.

PMID- 14689363
TI  - Tenofovir-related Fanconi syndrome with nephrogenic diabetes insipidus in a
      patient with acquired immunodeficiency syndrome: the role of lopinavir-ritonavir
      didanosine.
AB  - Tenofovir-related tubular damage, like all other recently reported cases,
      occurred in patients receiving the protease inhibitor (PI) ritonavir, often with
      lopinavir. Increased plasma concentrations of didanosine were also observed after
      the addition of tenofovir. It was suspected that tenofovir with PIs interacted
      with renal organic anion transporters, leading to nephrotoxic tubular
      concentrations of tenofovir and systemic accumulation of didanosine. Until there
      is a better understanding of these interactions, close monitoring is recommended
      for patients receiving tenofovir, PIs, and didanosine.

PMID- 14689364
TI  - Schistosomiasis does not contribute to death or recurrence of nontyphoid
      Salmonella bacteremia in human immunodeficiency virus-infected Malawian adults.
AB  - Nontyphoid Salmonella (NTS) bacteremia has a very high mortality and recurrence
      rate among human immunodeficiency virus (HIV)-infected Malawian adults.
      Concurrent schistosomal infection might cause persistence of NTS infection and
      poor response to antibiotic therapy. Therefore, we tested serum samples for
      Schistosoma-specific circulating anodic antigen to diagnose coinfection with
      schistosomiasis among consecutive HIV-positive adults with NTS bacteremia. The
      results suggest that active schistosomiasis is not associated with adverse
      outcome of NTS bacteremia in this population, in contrast to other groups.

PMID- 14689366
TI  - Blocking the renin-angiotensin-aldosterone system or lowering the blood pressure:
      does EUROPA help?
AB  - The EUropean trial on Reduction Of cardiac events with Perindopril in stable
      coronary Artery disease (EUROPA) demonstrated that the angiotensin- converting
      enzyme inhibitor, perindopril, compared with placebo, in patients with
      established coronary artery disease, reduced cardiovascular endpoints by 20% over
      a four-year follow-up period. Although the authors of this study claim that the
      risk reduction was best explained by blockade of the renin-angiotensin
      aldosterone system, reference to recent meta-analyses of blood pressure (BP)
      lowering trials provides compelling evidence that the benefits observed in the
      trial could be explained by the 5/2 mmHg BP difference between active and placebo
      treatments.

PMID- 14689367
TI  - Subfornical organ lesion attenuates chronic hypotensive effects of losartan in
      salt-replete rats.
AB  - HYPOTHESIS/INTRODUCTION: Circumventricular organs are central nervous system
      brain sites thought to participate in neuroendocrine regulation of neural output.
      We have previously demonstrated a profound chronic hypotensive response to the
      angiotensin II (Ang II) AT(1) antagonist, losartan (10 mg/kg/day), in normal
      rats. In addition, we have demonstrated that the area postrema, one of the
      circumventricular organs, partially mediates this response. The subfornical organ
      (SFO) is another circumventricular organ which has been shown to mediate actions
      of Ang II. The present study was designed to test the hypothesis that the SFO
      mediates the chronic hypotensive effects of losartan in normal rats. MATERIALS
      AND METHODS: Rats were randomly chosen for lesion of the SFO or sham operation
      and instrumented with intravenous catheters and radiotelemetric blood pressure
      transducers. After a control period, rats were infused with losartan (10
      mg/kg/day) for nine days. Mean arterial pressure and heart rate responses were
      measured continuously throughout the protocol and examined as 12-hour day/night
      averages. RESULTS: By day 7 of losartan treatment, night-time mean arterial
      pressure had dropped to 75+2 mmHg in sham rats (n=8) but only to 83+2 mmHg in SFO
      lesioned rats (n=10). This trend continued throughout the treatment protocol.
      CONCLUSIONS: These results suggest that the SFO partially mediates the chronic
      hypotensive effects of chronic losartan treatment in normal rats.

PMID- 14689368
TI  - Combined renin-angiotensin system blockade and dietary sodium restriction impairs
      cardiomyocyte contractility.
AB  - INTRODUCTION: Blockade of the renin-angiotensin system (RAS) by combined
      angiotensin-converting enzyme inhibitor and angiotensin type 1 receptor (AT(1))
      antagonist treatment with reduced dietary sodium intake produces suppression of
      cardiac growth and regression of cardiac hypertrophy. The purpose of this study
      was to investigate whether cardiac growth suppression by combined RAS blockade
      under conditions of dietary sodium restriction is associated with cardiomyocyte
      atrophy and contractile dysfunction and whether this intervention modifies
      cardiomyocyte inotropic responsiveness to angiotensin II (Ang II). METHODS: Rats
      were fed a high (4% w/w) or low (0.2% w/w) NaCl diet for six days. Both groups
      were then given a combined intraperitoneal injection of perindopril (6 mg/kg/day)
      and losartan (10 mg/kg/day) with maintained dietary treatment for another seven
      days. At the end of the treatment period, animals were anaesthetised and their
      hearts were removed and weighed. Left ventricular cardiomyocytes were isolated by
      enzymatic dissociation and cell dimensions were evaluated. A line scan camera and
      digital imaging technique were used to assess cardiomyocyte contraction and
      inotropic responses to exogenous Ang II (10 to 10(-8) M). RESULTS: Dietary
      treatment alone had no effect on body growth, whereas combined RAS blockade
      suppressed somatic growth in the low sodium (LS) group, compared with the high
      sodium (HS) group. This growth suppression in the LS group was also evident in
      the heart at the organ and cellular level. Studies of cardiomyocyte contraction
      showed that myocytes from the LS group exhibited contractile instability and
      depression of contractile performance. Compared with the HS group, myocytes from
      the LS group showed a significant reduction in maximum cell shortening (6.40+0.17
      vs. 7.32+0.16% resting length, p<0.05), and maximum rate of shortening (3.85+0.14
      vs. 4.29+0.11 cell length/ms, p<0.05). Myocytes of the HS group exhibited
      negative inotropic responses to Ang II at all concentrations tested, with a
      significant reduction in maximum cell shortening by 11 16% after 12 minutes
      peptide exposure (p<0.05 vs. non-treated control). In comparison, Ang II elicited
      both positive and negative responses in myocytes from the LS group, with a
      predominant negative inotropic effect. CONCLUSIONS: This study provides evidence
      that combined RAS blockade treatment under restricted sodium intake conditions
      can impair cardiomyocyte contractile function in association with cardiomyocyte
      growth suppression. Chronic RAS blockade qualitatively alters the intrinsic
      inotropic status and responsiveness of ventricular cardiomyocytes, and this shift
      is further modulated by dietary sodium intake conditions.

PMID- 14689369
TI  - Impaired neuronal and vascular responses to angiotensin II in a rabbit congestive
      heart failure model.
AB  - Congestive heart failure (CHF) is characterised by activation of the renin
      angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS).
      Both systems are known to interact and to potentiate each other s activities. We
      recently demonstrated that angiotensin II (Ang II) enhances sympathetic nerve
      traffic via prejunctionally-located AT1-receptors. At present, little is known
      about the effects of Ang II at the level of the sympathetic neurones in CHF.
      Accordingly, we investigated the effect of Ang II in the presence and absence of
      the AT1-receptor antagonist, eprosartan, on stimulation-induced nerve traffic in
      isolated thoracic aorta preparations obtained from rabbits suffering from
      experimentally-induced CHF. Control-preparations were obtained from age-matched
      animals. Sympathetic activity was assessed by a [3H]noradrenaline spill-over
      model. Additionally, Ang II constrictor responses were compared between CHF and
      control vessels in the presence and absence of eprosartan. Additionally, to study
      postjunctional facilitation, the effects of Ang II on postsynaptic a-adrenoceptor
      mediated responses were studied using noradrenaline. Stimulation-evoked SNS
      neurotransmission was similar in both groups (CHF versus control). Ang II (0.1 nM
      0.1  M) caused a concentration-dependent increase of the stimulation-evoked
      sympathetic outflow in both groups, with a maximum at 10 nM (control [n=7],
      FR2/FR1 2.03+0.11 and CHF- preparations [n=7], FR2/FR1 1.71+0.07). The
      enhancement by Ang II was decreased in CHF- preparations compared with controls
      (p<0.05). Eprosartan concentration-dependently attenuated the Ang II-enhanced (10
      nM) sympathetic outflow in both CHF- and control preparations. The sympatho
      inhibitory potency of eprosartan was similar in both groups (control pIC50 8.81
      0.31; CHF 8.65+0.42). Ang II (1 nM 0.3  M) concentration-dependently increased
      the contractile force in control preparations (Emax 21.64+3.86 mN, pD2 7.63+0.02,
      n=7). Eprosartan (1 nM 0.1  M) influenced the Ang II- contractions via a mixed
      form of antagonism. In CHF-preparations, Ang II caused impaired vascular
      contraction. The KCl-induced contraction was decreased in the CHF- compared with
      control preparations (13.02+0.64 mN versus 30.40+0.89 mN). The relative Ang II
      contraction (% of KCl) was also decreased (2.3% vs. 58.0%). Concentration
      response curves to noradrenaline (%KCl) were similar (control pD2 6.93+0.05, Emax
      131.0+2.7; CHF pD2 7.00+0.05, Emax 136.7+2.6) (p>0.05) and were not affected by
      Ang II. We conclude that Ang II-enhanced sympathetic neurotransmission is
      mediated by the prejunctional AT1-receptor in both control and CHF-preparations.
      The decreased facilitation of SNS effects by Ang II may be explained by down
      regulation or desensitisation of the neuronal AT1-receptor. Additionally, the
      aortic contractile capacity in heart failure rabbits appears to be decreased,
      probably as a result of heart failure-associated neuroendocrine and functional
      changes.

PMID- 14689370
TI  - Neutral endopeptidase expression in mesangial cells.
AB  - In the kidney, neutral endopeptidase (NEP) is implicated in the metabolism of
      several peptides involved in blood pressure and sodium homeostasis control, such
      as the atrial natriuretic peptide, bradykinin and angiotensin I. Due to its
      physiological importance in the modulation of pressor responses, the presence of
      NEP in mouse mesangial cells has been investigated, since these cells control
      glomerular function and are able to synthesise components of the renin
      angiotensin system. A NEP-like activity (NEP-like) that cleaves the fluorogenic
      substrates Abz-BKQ-EDDnp and Abz-DRRL-EDDnp was purified from mesangial cell
      lysate by ion-exchange, followed by gel filtration chromatography. The enzyme was
      able to hydrolyse bradykinin at the G4-F5 peptide bond and was inhibited by
      thiorphan. A pH study established that enzyme activity was maximal at pH 7.5 and
      the determined K(m) was 4.86  M using Abz-DRRL-EDDnp as substrate. NEP-like was
      recognised by monoclonal anti-NEP and had a molecular mass of 95 kDa. The
      purified enzyme was sequenced and showed similarity with human, rat, mouse and
      rabbit NEPs. We isolated, for the first time, NEP-like from mesangial cells. This
      enzyme could have an important role in the renal physiology by its action upon
      different peptides that are able to alter renal haemodynamics.

PMID- 14689371
TI  - Reduction (TELMAR) as assessed by magnetic resonance imaging in patients with
      mild-to-moderate hypertension--a prospective, randomised, double-blind comparison
      of telmisartan with metoprolol over a period of six months rationale and study
      design.
AB  - The Telmisartan Effectiveness on Left ventricular MAss Reduction (TELMAR) trial
      will assess the effect of the angiotensin II (Ang II) receptor blocker,
      telmisartan, on left ventricular hypertrophy (LVH) compared with the b-blocker,
      metoprolol, at similar antihypertensive doses. The rationale is that
      antihypertensives reduce LVH, a cardiac adaptation to pressure overload,
      principally by pressure-related effects. Ang II plays a key role in pressure
      independent mechanisms causing LVH, and angiotensin-converting enzyme (ACE)
      inhibitors induce more pronounced LVH regression than some other
      antihypertensives. Blocking Ang II Type 1 receptors may be more effective than
      ACE inhibition in reducing LVH. TELMAR is a prospective, randomised, double
      blind, double-dummy, parallel-group trial. A total of 140 patients (age 18 80
      years) with uncontrolled essential hypertension (mean daytime systolic blood
      pressure [SBP] >140 mmHg or diastolic blood pressure [DBP] >90 mmHg and/or night
      time SBP >120 mmHg or DBP >70 mmHg, measured by ambulatory blood pressure
      monitoring [ABPM]) and left ventricular mass index related to height (LVMI) >0.8
      g/cm for females, >1.1 g/cm for males (defined by magnetic resonance imaging
      [MRI]) will be randomised to once-daily telmisartan or metoprolol. The
      telmisartan dose will be 40 mg for the first two weeks, 80 mg for 5.5 months and
      40 mg for the last two weeks. Metoprolol will be given at a dose of 47.5 mg for
      two weeks, 95 mg for 5.5 months and 47.5 mg for two weeks. Concomitant add-on
      medication with hydrochlorothiazide and amlodipine will be allowed. The primary
      endpoint is the percentage change in LVMI at treatment end versus baseline, using
      MRI. Secondary variables include blood pressure changes and response rates
      assessed by ABPM and manual cuff sphygmomanometry, and end-systolic wall stress,
      systolic left ventricular function (LVF) and diastolic LVF determined by MRI. A
      separate study was performed prior to the main trial to define the normal range
      of MRI data in an age-matched population.

PMID- 14689372
TI  - Haemodynamic and pulse wave responses to intravenous infusions of angiotensin II
      during chronic telmisartan therapy in normal volunteers.
AB  - INTRODUCTION: This study investigated the central haemodynamic, blood pressure
      (BP) and pulse wave responses to progressively increasing infusion rates of
      intravenous angiotensin II (Ang II) in normal volunteers during chronic therapy
      with telmisartan or placebo. MATERIALS AND METHODS: Ten normal volunteers, aged
      21 33 years, completed a randomised, double-blind crossover study. Ang II was
      infused intravenously at increasing infusion rates (0 512 ng/minute) at the end
      of one week of telmisartan therapy (40 80 mg/day) and one week of placebo
      therapy. BP, central haemodynamics and pulse wave parameters were monitored
      continuously using a CardioDynamics Recorder, a Pulse Tracer Recorder and a
      Finipress Recorder. RESULTS: Baseline diastolic BP (57+12 vs. 67+13 mmHg) and
      pulse wave reflection index (RI) (38.4+18.6 vs. 60.6+12.5%) were significantly
      lower on telmisartan than on placebo therapy. Cardiac index (CI), systolic BP,
      systemic vascular resistance index (SVRI), RI and pulse wave stiffness index (SI)
      were all significantly increased in a dose-dependent manner by Ang II on placebo
      therapy. Telmisartan significantly (p<0.05) attenuated all of these responses to
      Ang II. Increases in BP during Ang II infusion were associated with increases in
      SVRI and CI. CONCLUSIONS: Telmisartan effectively blocked the effects of
      intravenous Ang II on CI, BP, RI and SI in healthy volunteers. Changes in CI make
      a major contribution to increase in BP response to intravenous Ang II in normal
      volunteers.

PMID- 14689373
TI  - Expensive blood safety technologies: understanding and managing cost and access
      to-care issues.
AB  - With a succession of recent blood safety enhancements driving up blood component
      costs for their hospital customers, the blood banking industry has called for
      changes in Medicare inpatient payment policy to narrow the gap between costs and
      reimbursement. In the specific case of leukoreduction of red blood cells, the
      interplay of intense cost pressures and the absence of authoritative clinical
      practice guidelines have created wide hospital-to-hospital disparities in patient
      access to leukoreduced blood components. This review examines the financial
      implications of costly nonmandated blood safety-related technologies for US
      hospitals, using leukoreduced red blood cells as a case example. An approach is
      offered to (1) standardize clinical practice with respect to the administration
      of nonmandated blood component innovations, (2) reduce the influence of hospital
      financial priorities on patient access, and (3) better address medicoeconomic
      tradeoff concerns.

PMID- 14689374
TI  - Improving the bacteriological safety of platelet transfusions.
AB  - Despite the increased application of aseptic techniques for blood collection and
      the preparation of platelet concentrates, morbidity and mortality arising from
      the transfusion of bacterially contaminated allogeneic platelet products persist.
      This problem exists because stored platelet concentrates represent a nearly ideal
      growth medium for bacteria and because they are stored at temperatures (22
      degrees +/- 2 degrees C) that facilitate bacterial growth. The presence of
      bacteria in blood components including platelets has been a problem for many
      decades and currently is the most common microbiological cause of transfusion
      associated morbidity and mortality. A variety of strategies have been devised
      and/or proposed in an attempt to try to reduce the risk of transfusion-associated
      sepsis. These include pretransfusion bacterial detection, efforts to reduce the
      likelihood of bacterial contamination, the optimization of blood product
      processing and storage, reducing recipient exposure, and the introduction of
      pathogen inactivation methodology. With regard to doing bacterial detection, a
      number of automated detection systems have become available to test for
      contaminated platelet components, but their utility to some extent is restricted
      by the time they take to indicate the presence of bacteria and/or their lack of
      sensitivity to detect initially low bacterial loads. A variety of other
      approaches has been shown to reduce the risk of bacterial contamination and
      include filtration to remove leukocytes and bacteria, diversion of the initial
      aliquot of blood during donation, and improved donor skin disinfection. Platelet
      pathogen inactivation methods under investigation include the addition of L
      carnitine, gamma-irradiation, riboflavin plus UVA irradiation, and amotosalen HCl
      plus UVA irradiation. The latter process is licensed for clinical use with
      platelets in some countries in Europe. All of these approaches, either
      collectively or individually, hold considerable promise that the prevalence of
      adverse events associated with bacteria in platelet products will decline
      significantly in the very foreseeable future.

PMID- 14689375
TI  - Review of the quality monitoring methods used by countries using or implementing
      universal leukoreduction.
AB  - Several countries are implementing or have implemented universal leukoreduction
      (ULR). Specifications, leukocyte counting, and monitoring methods were essential
      elements in achieving process confidence and conformance. A review of these
      protocols is presented. A questionnaire was prepared, agreed, and circulated, and
      responses were collated. Different specifications have been adopted as well as
      disparate approaches to leukocyte counting and residual leukocyte monitoring.
      Parametric, nonparametric, and pass-rate methods of analysis were used. Despite
      these differences, users were satisfied that the methodologies were providing
      assurance of component quality.

PMID- 14689376
TI  - Managing recalls and withdrawals of blood components.
AB  - Donor centers are issuing a growing number of recalls and market withdrawals to
      hospital transfusion services about blood components. More than 1 in 2,000 units
      were recalled in the late 1990s in the United States. The most common reason for
      these notices from donor centers is postdonation donor information. Most of these
      units had been transfused, and many present a "risk of a risk" (ie, a problem
      might have been present that might have affected the recipient). A few
      regulations and standards address recalls in general terms, but transfusion
      services generally have wide discretion in the management of specific common
      recall problems. The Food and Drug Administration (FDA) is now including
      posttransfusion evaluations in its guidelines for emerging infectious threats to
      the blood supply. We suggest that hospital transfusion services should have
      standard operating procedures for managing recalls and that the hospital
      transfusion committee and the quality management program should provide local
      input or oversight. Using the FDA's categories of donor center biological product
      deviations, we provide recommendations to consider for when to notify the
      recipient's physician, after postdonation information is received about a
      previously transfused blood component. More study of this important everyday
      issue in transfusion medicine is highly desirable.

PMID- 14689377
TI  - HTLV-I/II prevalence in different geographic locations.
AB  - Human T-cell lymphotropic virus (HTLV) type I (HTLV-I) is the etiological agent
      of adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP). HTLV-II is a closely related virus, and this infection is
      not clearly associated with clinical disease, although neurologic disorders are
      observed resembling HAM/TSP. Prevalence rates for HTLV-I infection in the general
      population are greater than 1% in the Caribbean Basin, Central Africa, and South
      Japan. In most other areas in the world, as far as we know, HTLV-I/II infections
      are mainly found in high-risk groups (ie, immigrants from endemic areas, their
      offspring, their sexual contacts and in patients and intravenous injection users
      attending sexually transmitted disease clinics). Also, a high rate of infection
      for both HTLV-I and HTLV-II infection was observed in the native Amerindian
      population in North America as well as South America. Blood donors are routinely
      screened for HTLV-I/II in North America, several countries in Europe, Japan, and
      Taiwan.

PMID- 14689378
TI  - L-carnitine and its possible role in red cell and platelet storage.
AB  - The storage of red cells or platelets in the liquid state results in changes in
      quality over time. These changes are collectively known as the storage lesion and
      are associated with decreased in vivo viability and functionality. Modification
      of the components of the liquid milieu could favorably influence these changes. L
      carnitine is a naturally occurring compound, which is best known for its role in
      facilitating the transport of long chain fatty acids across the mitochondrial
      membrane. An additional role for this compound may also exist as a reservoir of
      acylcarnitines to replace oxidized fatty acids in membrane phospholipids. In
      experimental studies, L-carnitine has been shown to reduce hemolysis and to
      improve in vivo survival in nonleukoreduced red cells. This effect on hemolysis
      appears to be attenuated by prestorage leukoreduction, but the practical benefit
      of this effect to transfusion recipients is unclear. L-carnitine has also been
      shown to reduce glycolysis and maintain a better pH in liquid stored platelets.
      This effect could result in extended platelet storage to 7 or 10 days. Based on
      such results, a role for L-carnitine as an additive to improve platelet quality
      in extended platelet storage is suggested.

PMID- 14689385
TI  - Enervated and exhausted or energized and enthused?

PMID- 14689386
TI  - Honoring diversity: First do no harm.

PMID- 14689387
TI  - The faculty role in assuring patient safety.

PMID- 14689388
TI  - Science and freedom in a democracy.

PMID- 14689389
TI  - Peer mentoring for tenure-track faculty.
AB  - Four tenure-track nursing faculty members at a large, research-intensive
      university came together to help each other learn the role of faculty scholar and
      to provide discipline, critique, and collegiality for each other with the goal of
      building research careers. Peer mentoring is usually construed more as senior
      faculty mentoring newer faculty. In this model, new faculty members mentor each
      other based on the knowledge gained in their doctoral programs and through
      sharing experiences with their own mentors. The value of this strategy includes
      building relationships among diverse faculty members, creating opportunities for
      collaboration on research projects, and developing camaraderie among members that
      might not otherwise develop. One year after implementing this innovative strategy
      for faculty peer mentoring, group members report success in individual and
      collective scholarship productivity, more research collaboration, improved mutual
      expertise, and stronger relationships with each other.

PMID- 14689390
TI  - The influence of concept mapping on critical thinking in baccalaureate nursing
      students.
AB  - This article describes a quasi-experimental study that used a pretest-posttest
      design with a control group to evaluate the effectiveness of concept mapping in
      developing critical thinking skills in baccalaureate nursing students. A
      convenience sample (n = 76) was randomly assigned to experimental (n = 44) and
      control (n = 32) groups. The experimental group was taught to use concept mapping
      of patient information to prepare for clinical experiences. The control group was
      taught to use traditional nursing care plans. Critical thinking skills were
      measured with the California Critical Thinking Skills Test, which yielded six
      scores: an overall score and five subscales (analysis, evaluation, inference,
      deductive reasoning, and inductive reasoning). A significant difference (p <.05)
      was found between the mean pretest and posttest scores and each subscale. Post
      hoc tests found differences between groups to be insignificant, while various
      differences within a group were significant. Experimental-group scores improved
      significantly (p <.05) on the overall score and the analysis and evaluation
      subscales, while control-group scores improved significantly only on the
      evaluation subscale and declined significantly on the inference subscale. The
      findings suggest that concept mapping is effective in helping students develop
      critical thinking skills.

PMID- 14689391
TI  - Blended roles: preparing the advanced practice nurse educator/clinician with a
      Web-based nurse educator certificate program.
AB  - Changing demographics, a nursing shortage, and various societal changes
      underscore the need for nurse educators and new nurse educator programs. This
      article describes a Web-based nurse educator program designed to prepare advanced
      practice nurses for faculty roles while simultaneously preparing them as
      clinicians. Guided by adult education theory and self-directed learning theory,
      the Web-based Nurse Educator Certificate (four Web-based nurse educator courses
      including a teaching practicum) has been developed and offered to clinical
      master's and postmaster's students. This article also describes student work with
      mentors, interactive Web-based teaching strategies, portfolios, graduate
      competencies, and initial evaluative data. In the first two years of the program,
      48 students have taken at least one course in the Nurse Educator Certificate
      program and eight students have completed it. A Web-based nurse educator
      certificate program, as part of a clinical master's or postmaster's program, has
      the potential to help meet the faculty shortage.

PMID- 14689392
TI  - Education of nurse practitioners in academic nurse-managed centers: student
      perspectives.
AB  - Clinical experiences for advanced practice nurses are increasingly a challenge.
      Finding settings that demonstrate primary care nursing practice in its finest
      form can be difficult. This article reports on nurse practitioner (NP) student
      feedback on clinical placements in the academic nurse-managed centers (ANMCs)
      associated with four Michigan schools or colleges of nursing. Student feedback
      was solicited over three years through site and preceptor evaluation tools and
      focus groups. Students were overwhelmingly satisfied with their experience in
      ANMCs. Being mentored by an NP preceptor in an ANMC was a valuable experience for
      students. They valued the role modeling of the NP and the quality of their
      preceptors' instruction. Students stated that the nursing model of care to which
      they were exposed was congruent with classroom learning. They reported learning
      to apply an understanding of their patients' economic, social, and cultural
      situations to treatment decisions and patient-education efforts and learning to
      understand the role of community-based care. One limitation of ANMCs from the
      students' perspective was a relatively low volume of patients, particularly in
      the initial years. However, the benefit of having time to spend with clients and
      to reflect on clinical practice was also articulated.

PMID- 14689393
TI  - Exploring and developing a college's community of interest: an appreciative
      inquiry.
AB  - This study examined what the Commission on Collegiate Nursing Education
      identifies as a college of nursing's internal and external "community of
      interest." Using "appreciative inquiry" in this study of a college campus, we
      examined the parts of the historical past that the community believed should be
      maintained, its vision of excellence for the college, the ways in which the
      vision could be realized, and its part in fulfilling the expectations of a
      shared, co-created vision. Investigators collected data using a self-developed,
      one-on-one interview and focus-group format and analyzed the data using content
      analysis. The findings suggest that the community shared values of preserving the
      college's past and of its vision for the college's future. However, it differed
      in the means of putting its co-created vision into practice and in defining its
      contributions in realizing the vision it created for the college.

PMID- 14689394
TI  - Analysis of end-of-life content in critical care nursing textbooks.
AB  - Nurses have identified a need for improving their knowledge and skills in
      providing end-of-life care. Critical care nursing textbooks can serve as an
      important source of information on end-of-life care for critical care nurses.
      Hence, an analysis of end-of-life content in 14 critical care nursing textbooks
      was conducted. Critical care nursing textbooks used for review were published in
      1995 or later and identified from the libraries at the University of Wisconsin
      Madison and Brigham Young University. The end-of-life content areas identified by
      the American Association of Colleges of Nursing (AACN), under which the AACN end
      of-life competencies for undergraduate nursing students can be taught, were used
      as a framework for assessing the presence or absence of end-of-life content in
      the textbooks. When end-of-life content was present, two reviewers judged whether
      the information was helpful. Four additional end-of-life content areas were
      identified in some textbooks during the study, and reviewers also judged whether
      these were helpful. None of the textbooks had end-of-life content in all the
      content areas used for the analysis. Three textbooks did not contain any end-of
      life content.

PMID- 14689395
TI  - Standards of holistic nursing practice as guidelines for quality undergraduate
      nursing curricula.
AB  - The accreditation criteria of the Commission for Collegiate Nursing Education
      (CCNE) direct faculty to select nationally developed standards for professional
      practice to guide curricula and to articulate curriculum outcomes. Recently, the
      CCNE proposed that all undergraduate programs should adopt the American
      Association of Colleges of Nursing (AACN) Essentials of Baccalaureate Education
      as one set of national standards for undergraduate and prelicensure programs.
      Standards of Holistic Nursing Practice, developed by the American Holistic
      Nurses' Association, is an additional set of standards that assists in defining
      quality for undergraduate nursing education. Standards of Holistic Nursing shares
      major concepts with Essentials; however, it accentuates the concepts of nurse
      self-care, articulated nursing theory as a foundation for practice, managing the
      care environment to promote healing, and care of the environment as essential to
      professional practice. These standards do not change the care being provided by
      professional nurses adhering to nursing theory and current evidence, but they do
      raise awareness and change emphasis of practice to reflect a holistic
      perspective. Used together, Standards and Essentials provide complementary
      guidelines for curricula-preparing professional nurses to care for client and
      self.

PMID- 14689396
TI  - Complementary therapies and healing practices: faculty/student beliefs and
      attitudes and the implications for nursing education.
AB  - The purpose of this study was to describe the knowledge and attitudes of nursing
      faculty and students (BSN and MS) regarding complementary/alternative therapies
      (C/AT) and their integration into nursing practice. Implications for curricular
      and faculty development were also identified. A cross-sectional survey (n = 170)
      of graduating BSN students (n = 73) and MS and PhD students (n = 47) and faculty
      (n = 50) was conducted in a university-based nursing program. The self
      administered questionnaire contained 134 forced choice items. Questions assessed
      attitudes and knowledge about training in, personal use of, perceived barriers
      to, and intent to integrate C/AT into clinical practice. Over 95 percent of the
      students and faculty agreed that clinical care should integrate the best of
      conventional and C/AT practices. Few had received formal C/AT education; the
      highest number had received some education about massage, music, prayer/spiritual
      healing, and therapeutic/healing touch. They desired more education but not
      necessarily the skills to perform these therapies themselves. Faculty and
      students expressed positive attitudes about incorporating C/AT into curricula and
      nursing practice. Current knowledge lags behind interest, however, suggesting a
      situation ripe for change. The most important perceived barrier to incorporation
      was lack of evidence. Curricular change is needed to fully integrate C/AT in
      nursing programs at all levels; faculty development and nursing research is
      needed to facilitate these changes.

PMID- 14689404
TI  - An anesthesiologist for all pediatric cardiac catheterizations: luxury or
      necessity?

PMID- 14689405
TI  - Which anesthetic agent alters the hemodynamic status during pediatric
      catheterization? Comparison of propofol versus ketamine.
AB  - OBJECTIVE: To compare the effects of propofol and ketamine on systemic and
      pulmonary circulations in pediatric patients scheduled for elective cardiac
      catheterization. DESIGN: Prospective, randomized, and blinded. SETTING:
      University hospital. PARTICIPANTS: Children (n = 41) undergoing cardiac
      catheterization. INTERVENTIONS: All children were premedicated with oral
      midazolam 60 minutes before the procedure. Patients were separated into 3 groups
      according to shunts diagnosed by transthoracic echocardiography before the
      catheterization procedure: patients without cardiac shunt (Group I, n = 11), left
      to-right shunt (Group II, n = 12), and right-to-left shunt (Group III, n = 18). A
      continuous infusion of propofol (100-200 microg/kg/min) or ketamine (50-75
      microg/kg/min) was randomly started in all groups to obtain immobility during the
      procedure. Hemodynamic data, including systemic venous, pulmonary artery and
      vein, aortic saturations and pressures, were recorded; Qp/Qs were calculated. The
      same set of data was recorded before discontinuation of infusions at the end of
      the procedure. MEASUREMENTS AND MAIN RESULTS: After the propofol administration,
      in all 3 patient groups propofol infusion was associated with significant
      decreases in systemic mean arterial pressure. In groups with cardiac shunts
      (Group II and III), propofol infusion significantly decreased systemic vascular
      resistance and increased systemic blood flow, whereas pulmonary vascular
      resistance and pulmonary blood flow did not change significantly. These changes
      resulted in decreased left-to-right shunting and increased right-to-left
      shunting; the pulmonary-to-systemic flow ratio decreased significantly. On the
      other hand, after ketamine infusion, systemic mean arterial pressure increased
      significantly in all patient groups, but pulmonary mean arterial pressure,
      systemic vascular resistance, and pulmonary vascular resistance were unchanged.
      CONCLUSION: In children with cardiac shunting, the principal hemodynamic effect
      of propofol is a decrease in systemic vascular resistance. In children with
      intracardiac shunting, this results in an increase in right-to-left shunting and
      a decrease in the ratio of pulmonary to systemic blood flow, which may lead to
      arterial desaturation. Ketamine did not produce these changes. The authors
      suggested that during cardiac catheterization in children, both the
      anesthesiologists and cardiologists need to know that anesthetic agents can
      significantly alter the hemodynamic status in children with complex congenital
      heart defects and affect the results of hemodynamic calculations that are
      important for decision-making and treatment of these patients.

PMID- 14689406
TI  - Propofol-ketamine mixture for anesthesia in pediatric patients undergoing cardiac
      catheterization.
AB  - OBJECTIVE: To evaluate the safety of a propofol-ketamine mixture to induce and
      maintain anesthesia in spontaneously breathing pediatric patents during cardiac
      catheterization. DESIGN: Prospective clinical study. SETTING: Departments of
      Cardiothoracic Surgery, Anesthesiology, and Pediatric Anesthesiology in a
      university hospital. PARTICIPANTS: Forty-five children aged 6 months to 16 years
      with ASA grade II to III undergoing cardiac catheterization. INTERVENTIONS:
      Continuous intravenous infusion of a mixture of propofol (4 mg/mL) and ketamine
      (2 mg/mL) with spontaneous ventilation. The infusion rate was changed and
      additional boluses of propofol or/and ketamine were given as needed. Hemodynamic,
      respiratory, and other variables were recorded during the procedure and recovery.
      RESULTS: Mean dose of ketamine was 26 +/- 8.3 microg/kg/min and of propofol, 68.3
      +/- 21.7 microg/kg/min. Changes in heart rate and mean arterial pressure of more
      than 20% from baseline were observed in 4 and 5 patients, respectively. A
      transient reduction in oxygen saturation because of hypoventilation was observed
      in 3 patients and responded to oxygen administration and manual assisted
      ventilation. No other complications were observed. CONCLUSIONS: The propofol
      ketamine mixture is a safe, practical alternative for general anesthesia in
      pediatric patients undergoing cardiac catheterization.

PMID- 14689407
TI  - The value of preoperative pharmacologic stress testing before vascular surgery
      using ACC/AHA guidelines: a prospective, randomized trial.
AB  - OBJECTIVE: To evaluate the validity of preoperative cardiac stress testing using
      clinical predictors from the American College of Cardiology/American Heart
      Association Guidelines on Perioperative Evaluation before Noncardiac Surgery in
      patients undergoing vascular surgery. DESIGN: Prospective, randomized pilot
      study. SETTING: Academic medical center. PARTICIPANTS: Patients undergoing
      elective abdominal aortic, infrainguinal, and carotid vascular surgery.
      INTERVENTIONS: After stratification by American College of Cardiology/American
      Heart Association (ACC/AHA) Guideline parameters, 99 patients were randomized to
      preoperative cardiac stress testing or to no stress testing and followed for up
      to 12 months postoperatively for adverse cardiac outcomes. MEASUREMENTS AND MAIN
      RESULTS: Before hospital discharge of 46 patients who underwent preoperative
      stress testing, 7 (15%) had inducible ischemia with no adverse postoperative
      cardiac outcomes, whereas only 1 (3%) of 39 patients (85%) with no ischemia had a
      nonfatal adverse cardiac outcome (p = not significant). Of 53 patients without
      preoperative stress testing, only 2 (4%) had a nonfatal adverse postoperative
      cardiac outcome. There were no cardiac deaths. At 12-month follow-up in 79 (80%)
      patients, there was 1 nonfatal adverse cardiac outcome (no stress test) and 1
      cardiac death (abnormal stress test), reflecting a 1% 12-month cardiac morbidity
      and mortality. CONCLUSION: In this small prospective, randomized study evaluating
      the validity of preoperative cardiac stress testing using ACC/AHA Guidelines
      before major vascular surgery, preoperative cardiac stress testing offered no
      incremental value for determining postoperative adverse cardiac outcomes. Larger
      randomized clinical trials are needed to confirm these findings.

PMID- 14689408
TI  - Association of intraoperative hypotension and pulmonary hypertension with adverse
      outcomes after orthotopic liver transplantation.
AB  - BACKGROUND: Various preoperative, surgical, and postoperative markers of impaired
      outcome after orthotopic liver transplantation have been reported, but the
      influence of intraoperative hemodynamic aberrations has not been thoroughly
      investigated. SETTING: University Hospital.Study design Retrospective cohort
      analysis. METHODS: The authors retrospectively reviewed computerized anesthesia
      records to determine associations between occurrences of abnormally low or high
      mean pulmonary artery pressure (MPAP), cardiac output, heart rate, systolic
      arterial pressure, diastolic arterial pressure, and mean arterial pressure (MAP)
      with negative surgical outcome. Negative surgical outcome was defined as poor
      early graft function, primary graft nonfunction, or death attributable to
      hemodynamic causes. RESULTS: Of 789 patients, 142 (18.0%) had negative surgical
      outcome. Controlling for the influence of United Network for Organ Sharing (UNOS)
      status > 1, long operation time, cold donor organ ischemia time, and donor age,
      the only hemodynamic parameters that were independently associated with negative
      surgical outcome were MAP < 40 mmHg at least once during the procedure (odds
      ratio [OR] 2.39, p = 0.0016) and MPAP > 40 mmHg at least 3 times during the
      procedure (OR 2.2, p = 0.035). The occurrence of MAP < 40 mmHg was temporally
      associated with donor graft reperfusion. Hepatic artery thromboses were not
      associated with hemodynamic aberrations. CONCLUSIONS: Hemodynamic events are
      independently associated with adverse outcomes after orthotopic liver
      transplantation.

PMID- 14689409
TI  - Quantitative analysis of left ventricular regional wall motion with color kinesis
      during abdominal aortic cross-clamping.
AB  - OBJECTIVES: The authors aimed to establish a technique for quantitative analysis
      of regional wall motion abnormality (RWMA) using color kinesis (CK) of
      transesophageal echocardiography (TEE) in surgical patients. This technique was
      used to determine whether RWMAs develop de novo after infrarenal aortic cross
      clamping in patients undergoing vascular surgery with a preoperative dipyridamole
      thallium stress test (DTST). DESIGN: An observational study. SETTING: University
      hospital. PARTICIPANTS: Thirty-eight patients undergoing infrarenal abdominal
      aortic aneurysm resection or aortofemoral bypass. MEASUREMENTS AND MAIN RESULTS:
      CK images of the left ventricle (LV) were obtained from the midventricular
      transgastric short-axis view before and after infrarenal aortic cross-clamping
      using TEE and analyzed off-line using custom software. The predictive value of
      the category "reversible perfusion defect" (RD) was also estimated from DTST for
      predicting new RWMAs with CK. CK analysis is suitable for clinical use based on
      the comparison with conventional two-dimensional echocardiogram measurements and
      interobserver variability. CK analysis showed all 7 patients with persistent
      perfusion defects on DTST had RWMAs. New RWMAs occurred in 2 of 9 patients with
      RD and in 2 of 15 patients with normal DTST, indicating that there was no
      significant difference between RD and normal DTST in the incidence of new RWMAs.
      CONCLUSIONS: A new method is available for clinical use, which is capable of
      visualizing RWMAs. These results suggest that new RWMAs introduced by aortic
      cross-clamping occur irrespective of the risk as assessed by preoperative DTST.
      CK with the new analysis method might be a useful tool to quantitatively evaluate
      RWMAs during surgery.

PMID- 14689410
TI  - Influence of isoflurane on left atrial function in dogs with pacing-induced
      cardiomyopathy: evaluation with pressure-volume relationships.
AB  - OBJECTIVE: The actions of volatile anesthetics on left ventricular (LV) function
      in normal and failing hearts have been previously evaluated, but the effects of
      these agents on left atrial (LA) function in the presence of LV dysfunction are
      unknown. The hypothesis was tested that isoflurane alters LA mechanics evaluated
      with pressure-volume relations. DESIGN: Prospective. SETTING: Laboratory.
      PARTICIPANTS: Barbiturate-anesthetized dogs (n = 8) were instrumented for
      measurement of aortic, LA, and LV pressures (micromanometers), and LA volume
      (epicardial orthogonal sonomicrometers) after 3 weeks of rapid ventricular pacing
      (220 beats/min). INTERVENTIONS: LA myocardial contractility (E(es)) was assessed
      with end-systolic pressure-volume relations. LA stroke work and reservoir
      function were assessed by A and V loop area, respectively, from the steady-state
      pressure-volume diagram. LA-LV coupling was determined by the ratio of E(es) to
      LV elastance (E(LV)). Dogs received 0.6, 0.9, and 1.2 minimum alveolar
      concentration isoflurane in a random manner, and LA function was determined after
      a 20-minute equilibration at each dose. MEASUREMENTS AND MAIN RESULTS: Isoflurane
      significantly (p < 0.05) decreased heart rate, mean arterial pressure, LV end
      systolic pressure, and LV +dP/dt(max). Isoflurane produced dose-related
      reductions in E(es) and E(es)/E(LV). Declines in LA stroke work, emptying
      fraction, reservoir volume, V loop area, and the active LA contribution to LV
      filling also occurred. CONCLUSIONS: The results indicate that isoflurane
      depresses LA myocardial contractility, impairs LA-LV coupling, and reduces active
      LA contribution to LV filling in dogs with pacing-induced cardiomyopathy. The
      impact of isoflurane on LA function in the presence of LV dysfunction has
      profound effects on cardiac performance.

PMID- 14689411
TI  - Pyruvate-enhanced cardioprotection during surgery with cardiopulmonary bypass.
AB  - OBJECTIVES: To determine whether pyruvate-fortified cardioplegia solution
      provides cardioprotection superior to lactate-based cardioplegia solutions in
      patients undergoing elective coronary revascularization, with specific attention
      to post-surgical recovery of left ventricular performance as well as biochemical
      markers of ischemic injury. DESIGN: Prospective, randomized, semi-blinded human
      trial. SETTING: Community-based academic medical center. PARTICIPANTS: Thirty
      adult patients undergoing elective coronary artery bypass graft surgery.
      INTERVENTIONS: Patients were randomized to two 4:1 blood cardioplegia solutions,
      one pyruvate enhanced and the other lactate based. Hemodynamic and laboratory
      variables were measured in all patients at pre-cross-clamp, post-cross-clamp, and
      4, 6, 8, and 12 hours after bypass. MEASUREMENTS AND MAIN RESULTS: Relative to
      lactate-based cardioplegia, pyruvate-fortified cardioplegia sharply increased
      left ventricular stroke work at 4 to 12 hours after bypass (p < 0.001), lowered
      coronary sinus troponin I and creatine phosphokinase-MB activities 67% (p <
      0.001) and 53% (p < 0.01), respectively, and increased coronary sinus hemoglobin
      O(2) saturation 18% (p < 0.001). Ten patients treated with lactate cardioplegia
      required beta-adrenergic inotropic support postbypass, but only 4 pyruvate
      treated patients required beta-adrenergic support (p = 0.067). Pyruvate
      cardioplegia shortened postsurgery hospitalization from 6.3 +/- 0.3 to 5.2 +/-
      0.1 days (p < 0.002). CONCLUSIONS: Pyruvate-fortified cardioplegia mitigated
      myocardial injury during coronary artery bypass surgery and facilitated
      postsurgical recovery of cardiac performance. Thus, pyruvate-enhanced
      cardioplegia may provide cardioprotection superior to lactate-based solutions
      during surgical cardiac arrest.

PMID- 14689412
TI  - Dose-related effects of theophylline added to modified Euro-Collins solution used
      for hypothermic preservation of lung.
AB  - OBJECTIVE: To investigate the dose-related effects of theophylline in prevention
      of ischemia-reperfusion injury of the lung. DESIGN: Experimental study. SETTINGS:
      University hospital. PARTICIPANTS: Thirty Wistar rats. INTERVENTIONS: In
      experimental group 1 (G-I) (n = 5) 20 mg/L, in G-II (n = 5) 100 mg/L, in G-III (n
      = 5) 400 mg/L, and in G-IV (n = 5) 1000 mg/L of theophylline was added to
      modified Euro-Collins solution and perfused the lungs. Lungs were extracted
      without an ischemic period in control group 1 (C-I) and perfused with modified
      Euro-Collins solution in control group 2 (C-II). Lungs were kept in a hypothermic
      state for 6 hours and then ventilated for 30 minutes with 100% O(2). MEASUREMENTS
      AND MAIN RESULTS: Tissue levels of dien congugate (DC) and malonylaldehyde (MDA)
      were measured. Comparison of 6 groups revealed statistically significant
      differences for DC and MDA (p < 0.0001 for both comparisons). Both DC and MDA
      levels of C-II were found to be higher than G-III and G-IV (p = 0.008). DC and
      MDA levels of G-III and G-IV were significantly lower than G-I and G-II (p =
      0.008 for all comparisons). CONCLUSION: The results of this study showed that 400
      mg/L and 1000 mg/L of theophylline added to the modified Euro-Collins solution
      decreased the intermediate products of lipid peroxidation. Theophylline merits
      further investigation in ischemia-reperfusion studies as a potentially beneficial
      agent.

PMID- 14689413
TI  - Lung isolation during port-access cardiac surgery: double-lumen endotracheal tube
      versus single-lumen endotracheal tube with a bronchial blocker.
AB  - OBJECTIVE: The purpose of this study was to compare the use of a double-lumen
      endotracheal tube to a single-lumen tube combined with a bronchial blocker for
      lung isolation during Port-Access cardiac surgery. DESIGN: Prospective,
      randomized, controlled trial. SETTING: Tertiary care university hospital.
      PARTICIPANTS: Thirty-two patients undergoing Port-Access cardiac surgery via a
      right minithoracotomy. INTERVENTIONS: Patients were randomized to intubation with
      either a left-sided double-lumen tube (double-lumen group) or a single-lumen tube
      with concomitant use of a bronchial blocker (blocker group). Comparisons between
      groups included (1) intubation time, (2) number of laryngoscopy attempts, (3)
      time required for tube exchange at the end of the operation, and (4) surgical
      satisfaction with the lung deflation (1-5 scale: 5 = excellent). MEASUREMENTS AND
      MAIN RESULTS: The initial intubation time was similar between groups (118 +/- 82
      seconds, double-lumen v 144 +/- 32 seconds, blocker; p = 0.2781). An additional
      105 +/- 37 seconds was needed to exchange the double-lumen tube at the end of the
      operation. The double-lumen group also required more laryngoscopy attempts
      compared with the blocker group (2.3 +/- 0.6, double-lumen v 1.1 +/- 0.4,
      blocker; p = 0.0001). The lung deflation was better in the double-lumen group (5
      [4-5], double-lumen v 4 [3-5], blocker, p = 0.0414). CONCLUSIONS: Compared with a
      single-lumen tube/bronchial blocker combination the double-lumen endotracheal
      tube required more laryngoscopy attempts and additional time to replace the tube
      at the end of the case but resulted in slightly better overall lung deflation.

PMID- 14689414
TI  - A comparison of CardioQ and thermodilution cardiac output during off-pump
      coronary artery surgery.
AB  - OBJECTIVE: To compare CardioQ esophageal Doppler cardiac output and
      thermodilution cardiac output during off-pump coronary artery bypass surgery.
      DESIGN: Prospective clinical study. SETTING: University-affiliated teaching
      hospital PARTICIPANTS: Adult patients (n = 20) undergoing elective coronary
      artery bypass surgery without cardiopulmonary bypass. MEASUREMENTS AND MAIN
      RESULTS: Three hundred thirty-one comparisons of simultaneous CardioQ and
      thermodilution cardiac outputs were made. The Pearson correlation coefficient for
      the pooled data was 0.62. Using a Bland-Altman approach, the overall bias was 
      0.56 L/min with a precision of 0.64 L/min. The 95% limits of agreement (bias +/-
      2 SD) were -0.56 +/- 1.28 L/min. For individual patients, the bias ranged from 
      1.35 L/min to 0.27 L/min and the precision from 0.24 L/min to 0.74 L/min.
      CONCLUSION: Because of the wide limits of agreement and the large interpatient
      differences in both bias and precision, the CardioQ esophageal Doppler cardiac
      output cannot currently be recommended as an alternative to thermodilution
      cardiac output during off-pump coronary artery bypass surgery.

PMID- 14689415
TI  - Echocardiographic localization of left ventricular free wall rupture after
      minimally invasive mitral valve replacement.

PMID- 14689416
TI  - Intraoperative transesophageal echocardiographic imaging of an intra-aortic
      balloon pump placed via the ascending aorta.

PMID- 14689417
TI  - Anesthetic management for a hypertensive patent ductus arteriosus (PDA) closure
      in a patient with surgically uncorrectable long-segment right pulmonary artery
      hypoplasia and a ventricular septal defect.

PMID- 14689418
TI  - Management of a bronchopleural fistula using differential lung airway pressure
      release ventilation.

PMID- 14689419
TI  - Acute normovolemic hemodilution: physiology, limitations, and clinical use.

PMID- 14689420
TI  - Case 6-2003: embolization of an atrial septal occluder device.

PMID- 14689421
TI  - Pro: Retrograde cerebral perfusion is useful for deep hypothermic circulatory
      arrest.

PMID- 14689422
TI  - Con: Retrograde cerebral perfusion is not an optimal method of neuroprotection in
      thoracic aortic surgery.

PMID- 14689423
TI  - Surgical approach for a patient with aortic stenosis and a frozen mediastinum.

PMID- 14689424
TI  - Asymmetric cerebral near-infrared oximetric measurements during cardiac surgery.

PMID- 14689427
TI  - Accurate placement of double-lumen tubes: clinical signs are important.

PMID- 14689428
TI  - Hemodynamic compromise after bougie placement.

PMID- 14689429
TI  - Facial nerve paralysis during cervical plexus block for carotid artery
      endarterectomy.

PMID- 14689430
TI  - The use of nitric oxide as part of the sweep gas infusion during cardiopulmonary
      bypass.

PMID- 14689443
TI  - The TIMPs tango with MMPs and more in the central nervous system.
AB  - The matrix metalloproteinases (MMPs) are a family of zinc-dependent extracellular
      proteases that have been implicated in CNS development and disease. Crucial
      homeostatic regulation of MMPs is mediated through the expression and actions of
      the tissue inhibitors of metalloproteinases (TIMPs). Although the TIMPs are
      recognized inhibitors of the MMPs, recent studies have revealed that these
      proteins also can exhibit biological activities that are distinct from their
      interactions with or inhibition of the MMPs. With our understanding of the roles
      of the TIMPs in the CNS continuously emerging, this review examines the current
      state of knowledge regarding the multifarious and novel functions of this family
      of proteins, with particular attention to their increasing potential in the
      development, plasticity, and pathology of the CNS.

PMID- 14689444
TI  - Isoform-specific knockout of FE65 leads to impaired learning and memory.
AB  - FE65 is a multimodular adapter protein that is expressed predominantly in brain.
      Its C-terminal phosphotyrosine interaction domain (PID) binds to the
      intracellular tail of the beta-amyloid precursor protein (betaPP), a protein of
      central importance to the pathogenesis of dementias of the Alzheimer type. To
      study the physiological functions of FE65, we generated a line of FE65 knockout
      mice via gene targeting. By Western analysis with a panel of FE65-specific
      antibodies, we demonstrate that the 97-kDa full-length FE65 (p97) was ablated in
      the mutant mice, and that a previously undescribed FE65 isoform with apparent
      molecular mass of 60 kDa (p60) was expressed in both wild-type and mutant mice.
      p60 had a truncated N-terminus and was likely to be generated through alternative
      translation. Expressions of the two isoforms appeared to be brain region distinct
      and age dependent. The p97FE65(-/-) mice were viable and showed no obvious
      physical impairments or histopathological abnormalities. However, p97FE65(-/-)
      and p97FE65(+/-) mice exhibited poorer performances than wild-type mice on a
      passive avoidance task when tested at 14 months (P <.05). p97FE65(-/-) mice at 14
      months also exhibited impaired hidden-platform acquisition (P <.05) and a severe
      reversal-learning deficit (P <.002) but normal visual-platform acquisition in the
      Morris water maze tests. Probe trials confirmed impairments in p97FE65(-/-) mice
      in relearning of new spatial information, suggesting a hippocampus-dependent
      memory-extinction deficit. Reduced secretion of Abeta peptides was observed in
      primary neuronal cultures of hybrids of p97FE65(-/-)/betaPP transgenic (Tg2576)
      mice. These studies suggest an important and novel function of FE65 in learning
      and memory.

PMID- 14689445
TI  - Genomic structure, cochlear expression, and mutation screening of KCNK6, a
      candidate gene for DFNA4.
AB  - KCNK6 encodes a tandem pore domain potassium channel, TWIK-2, that maps to
      chromosome 19. Both STS and linkage maps established KCNK6 as a positional
      candidate gene for DFNA4, a form of autosomal dominant nonsyndromic hereditary
      hearing loss. Identification and characterization of Kcnk6 expression within the
      mammalian cochlea established the gene as a functional candidate for DFNA4.
      Identification of Twik-2 expression in the mouse cochlea was initially
      established via RT-PCR assay of cochlear RNA. Subsequent immunoblot analysis of
      cochlear homogenate yielded a distinct 35-kDa band corresponding to the
      calculated molecular weight of the mouse Twik-2. Immunohistochemical studies
      localized Twik-2 expression in the cochlea predominantly within the stria
      vascularis. This vascular tissue borders the cochlear duct and is a critical
      regulator of potassium concentration in the endolymph. Genomic structure of TWIK
      2 was subsequently determined and shown to consist of three coding exons with
      splice acceptor and donor sites in accordance with the consensus GT-AG rule. Two
      separate DFNA4 families were screened for KCNK6 sequence alterations. No
      mutations were found, thus excluding TWIK-2 as the DFNA4 candidate disease gene.
      Nevertheless, expression of Twik-2 within the stria vascularis suggests a
      potential role for this protein as one of the terminal components of the
      potassium ion-recycling pathway that contributes toward its reabsorption into the
      endolymph.

PMID- 14689446
TI  - Distribution of sensorin immunoreactivity in the central nervous system of Helix
      pomatia: functional aspects.
AB  - Land snails belonging to the genus Helix are commonly used to study several
      behaviors and their plasticity at the cellular level. Because the knowledge of
      sensory neurons in these species is far from being complete, we have investigated
      the presence and distribution in Helix pomatia central nervous system of the
      immunoreactivity for sensorin, a peptide specific for mechanosensory neurons in
      Aplysia. We found that the majority of immunopositive cells were grouped in
      clusters located in all the central ganglia, except for the pedal ganglion, where
      only a single large neuron was stained. A symmetrical cluster of stained cells in
      the cerebral ganglia showed homology with the cerebral J clusters in Aplysia.
      Most of the somata of these Helix cerebral clusters send their axons in the
      ipsilateral cerebropedal connective and lip nerves and make monosynaptic
      connections with cells located in a medial adjacent cluster. This monosynaptic
      circuit can be reestablished in culture, where it shows homosynaptic depression
      as it does in the ganglionic preparation.

PMID- 14689447
TI  - Maturation of spiking activity in trout retinal ganglion cells coincides with
      upregulation of Kv3.1- and BK-related potassium channels.
AB  - Developmental changes in membrane excitability and the potassium channel profile
      were monitored in acutely isolated trout retinal ganglion cells by patch-clamp
      recording in combination with single-cell RT-PCR. During embryonic development in
      the egg, a sustained above-threshold stimulation of ganglion cells elicited in
      most cases only a single spike response. After hatching, the proportion of
      multiply spiking cells increased strongly and the ability of spike frequency
      coding was acquired. This was accompanied by the occurrence of a highly
      tetraethylammonium (TEA)- and quinine-sensitive delayed rectifier current, which
      gradually masked a rapidly inactivating A-type potassium current that was
      predominant at earlier stages. Pharmacology of the delayed rectifier current
      closely matched those of recombinant Traw1, a Kv3.1-related potassium channel in
      trout. The appearance of this current correlated closely with initial expression
      of Traw1 and Traw2 channel transcripts, as revealed by multiplex single-cell RT
      PCR, whereas mRNA, encoding Shaker-related channel genes in trout (termed Tsha1
      Tsha4), were already detectable at early embryonic stages. Iberiotoxin-sensitive,
      calcium-activated potassium currents (BK) were extremely low before hatching, but
      increased significantly thereafter. These developmental changes in potassium
      channel expression occurred after the arrival of retinal fibers in the optic
      tectum and the initiation of synapse formation in the visual center. It is
      suggested that early expressed Shaker-related potassium channels could act to
      influence neuronal differentiation, whereas proper neuronal signaling requires
      expression of Kv3.1- and BK-related potassium channels.

PMID- 14689448
TI  - Neuritogenic and survival-promoting effects of the P2 peptide derived from a
      homophilic binding site in the neural cell adhesion molecule.
AB  - The neural cell adhesion molecule (NCAM) plays a pivotal role in neural
      development, regeneration, and plasticity. NCAM mediates adhesion and subsequent
      signal transduction through NCAM-NCAM binding. Recently, a peptide ligand termed
      P2 corresponding to a 12-amino-acid sequence in the FG loop of the second Ig
      domain of NCAM was shown to mimic NCAM homophilic binding as reflected by
      induction of neurite outgrowth in hippocampal neurons. We demonstrate here that
      in concentrations between 0.1 and 10 microM, P2 also induced neuritogenesis in
      primary dopaminergic and cerebellar neurons. Furthermore, it enhanced the
      survival rate of cerebellar neurons although not of mesencephalic dopaminergic
      neurons. Moreover, our data indicate that the protective effect of P2 in
      cerebellar neurons was due to an inhibition of the apoptotic process, in that
      caspase-3 activity and the level of DNA fragmentation were lowered by P2.
      Finally, treatment of neurons with P2 resulted in phosphorylation of the ser/thr
      kinase Akt. Thus, a small peptide mimicking homophilic NCAM interaction is
      capable of inducing differentiation as reflected by neurite outgrowth in several
      neuronal cell types and inhibiting apoptosis in cerebellar granule neurons.

PMID- 14689449
TI  - Regulation of sphingomyelinases in cells of the oligodendrocyte lineage.
AB  - Controversy exists regarding the nature of the "executioner" sphingomyelinase
      (SMase) in cells and its subcellular localization. A new fluorescence-based assay
      with the substrate 6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine
      allowed rapid and reliable microassays of neutral (N) and acid (A) SMase activity
      in cell extracts from primary cultures of neonatal rat oligodendrocytes (OPC) and
      a human oligodendroglioma cell line (HOG). Total SMase activity was much higher
      in OPC than in HOG cells. Both staurosporine and tumor necrosis factor-alpha (TNF
      alpha) induced apoptosis and activated NSMase in a multiphasic manner in both OPC
      and HOG cells. The increase in caspase 8 activity preceded the 1 hr peak of
      NSMase activation, which was followed by caspase 3 activation. In contrast,
      ASMase activity, which constituted >90% of the total SMase activity, was
      unresponsive to proapoptotic drugs. Neither reducing ASMase levels by 50% by
      pretreatment with desipramine nor inhibiting sphingolipid synthesis by 50% with
      fumonisin B1 had any effect on cell death. Isolation of sphingolipid-rich plasma
      membrane microdomains (rafts) from the cells by sucrose density gradient
      ultracentrifugation revealed an enrichment of sphingomyelin, ceramide, and
      caspase 8. Proapoptotic drugs such as staurosporine promoted the translocation of
      NSMase to the raft fraction. In contrast, ASMase, other lysosomal hydrolases, and
      caspase 3 remained absent from rafts even after staurosporine treatment. The
      staurosporine-induced concomitant increase of ceramide in the raft fraction and
      caspase 3 in the cytosol could be mimicked by the addition of exogenous bacterial
      SMase. We conclude that caspase 8 activates NSMase in rafts in oligodendrocytes
      and that the downstream apoptotic signal is via caspase 3.

PMID- 14689450
TI  - The chemokine receptor CXCR4 and not the N-methyl-D-aspartate receptor mediates
      gp120 neurotoxicity in cerebellar granule cells.
AB  - The human immunodeficiency virus type 1 (HIV-1) glycoprotein gp120 causes
      neuronal cell death; however, the molecular mechanisms of the neurotoxic effect
      remain largely unresolved. It has been suggested that gp120 evokes cell death by
      inducing the release of neurotoxins, including glutamate. The objective of this
      work was to examine the role of glutamate in gp120-mediated neurotoxicity. We
      used as an experimental tool cerebellar granule cells prepared from 8-day-old rat
      cerebella, in which both glutamate and gp120 cause cell death. Cerebellar granule
      neurons were exposed to gp120 or glutamate alone or in combination with the
      glutamate receptor antagonist MK801 as well as other antiglutamatergic compounds.
      Cell viability was measured at various times by using several markers of cell
      death and apoptosis. MK801, at a concentration that blocked glutamate-induced
      neuronal cell death, failed to prevent gp120-mediated apoptotic cell death.
      Moreover, interleukin-10, which has previously been shown to block glutamate
      toxicity in these neurons, was not neuroprotective against gp120. Because gp120
      toxicity is mediated by activation of the chemokine receptor CXCR4, neurons were
      incubated with the CXCR4 inhibitor AMD3100. This compound prevented gp120- but
      not glutamate-mediated cell death. These findings suggest that gp120 is toxic to
      neurons even in the absence of the virus and that the toxic mechanism involves
      primarily activation of CXCR4 receptor. Therefore, antagonists to the CXCR4
      receptor may be more suitable compounds for inhibiting HIV-1 neurotoxicity.

PMID- 14689451
TI  - Oxidative stress induces p53-mediated apoptosis in glia: p53 transcription
      independent way to die.
AB  - Oxidative stress has been implicated in the pathogenesis of stroke, traumatic
      brain injuries, and neurodegenerative diseases affecting both neuronal and glial
      cells in the central nervous system (CNS). The tumor suppressor protein p53 plays
      a pivotal function in neuronal apoptosis triggered by oxidative stress. We
      investigated the role of p53 and related molecular mechanisms that support
      oxidative stress-induced apoptosis in glia. For this purpose, we exposed C6
      glioma cells and primary cultures of rat cortical astrocytes to an H(2)O(2)
      induced oxidative stress protocol followed by a recovery period. We evaluated the
      effects of pifithrin-alpha (PF-alpha), which has been reported to protect neurons
      from ischemic insult by specifically inhibiting p53 DNA-binding activity.
      Strikingly, PF-alpha was unable to prevent oxidative stress-induced astrocyte
      apoptosis. We demonstrate that p53 is able to mediate an apoptotic response by
      direct signaling at mitochondria, despite its transcriptional activity. The z-VAD
      fmk-sensitive apoptotic response requires a caspase-dependent MDM-2 degradation,
      leading to p53 mitochondrial targeting accompanied by cytochrome c release and
      nucleosomal fragmentation.

PMID- 14689452
TI  - Astrocytes in culture require docosahexaenoic acid to restore the n-3/n-6
      polyunsaturated fatty acid balance in their membrane phospholipids.
AB  - Docosahexaenoic acid (DHA), the main n-3 polyunsaturated fatty acid (PUFA) in
      membranes, is particularly abundant in brain cells. Decreased cerebral
      concentrations of DHA, resulting from dietary n-3 deficiency, are associated with
      impaired cognitive function. Because the cellular causes of this impairment are
      still unknown, we need in vitro models that mimic the variations in n-3/n-6 PUFA
      seen in vivo. We have compared the PUFA profiles of hamster astrocytes cultured
      in medium supplemented with long-chain PUFA [DHA and/or arachidonic acid (AA)]
      with those of brain tissue from hamsters fed an n-6/n-3 PUFA-balanced diet or one
      lacking n-3 PUFA. Astrocytes were obtained from the brain cortex of newborn
      hamsters and cultured in minimum essential medium + 5% fetal calf serum (FCS)
      supplemented with DHA and/or AA for 10 days. The astrocytes cultured in medium +
      FCS had low n-3 PUFA contents, comparable to those of brain tissue from hamsters
      fed an n-3-deficient diet. We have shown that astrocytes grown in medium
      supplemented with DHA and/or AA, plus alpha-tocopherol to prevent lipid
      peroxidation, incorporated large amounts of these long-chain PUFA, so that the n
      6/n-3 PUFA compositions of the phosphatidylethanolamine and phosphatidylcholine,
      the two main classes of membrane phospholipids, were greatly altered. Astrocytes
      cultured in medium plus DHA had a more physiological n-3 status, grew better, and
      retained their astrocyte phenotype. Thus astrocytes in culture are likely to be
      physiologically relevant only when provided with adequate DHA. This reliable
      method of altering membrane phospholipid composition promises to be useful for
      studying the influence of n-6/n-3 imbalance on astrocyte function.

PMID- 14689453
TI  - Estrogen interacts with the IGF-1 system to protect nigrostriatal dopamine and
      maintain motoric behavior after 6-hydroxdopamine lesions.
AB  - The most prominent neurochemical hallmark of Parkinson's disease (PD) is the loss
      of nigrostriatal dopamine (DA). Animal models of PD have concentrated on
      depleting DA and therapies have focused on maintaining or restoring DA. Within
      this context estrogen protects against 6-hydroxdopamine (6-OHDA) and 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions of the nigrostriatal DA pathway.
      Present studies tested the hypothesis that neuroprotective estrogen actions
      involve activation of the insulin-like growth factor-1 (IGF-1) system.
      Ovariectomized rats were treated with either a single subcutaneous injection of
      17beta-estradiol benzoate or centrally or peripherally IGF-1. All rats were
      infused unilaterally with 6-OHDA into the medial forebrain bundle (MFB) to lesion
      the nigrostriatal DA pathway. Tyrosine hydroxylase (TH) immunocytochemistry
      confirmed that rats injected with 6-OHDA had a massive loss of TH
      immunoreactivity in both the ipsilateral substantia nigra compacta (60% loss) and
      the striatum (>95% loss) compared to the contralateral side. Loss of TH
      immunoreactivity was correlated with loss of asymmetric forelimb movements, a
      behavioral assay for motor deficits. Pretreatment with estrogen or IGF-1
      significantly prevented 6-OHDA-induced loss of substantia nigra compacta neurons
      (20% loss) and TH immunoreactivity in DA fibers in the striatum (<20% loss) and
      prevented the loss of asymmetric forelimb use. Blockage of IGF-1 receptors by
      intracerebroventricular JB-1, an IGF-1 receptor antagonist, attenuated both
      estrogen and IGF-1 neuroprotection of nigrostriatal DA neurons and motor
      behavior. These findings suggest that IGF-1 and estrogen acting through the IGF-1
      system may be critical for neuroprotective effects of estrogen on nigrostriatal
      DA neurons in this model of PD.

PMID- 14689454
TI  - Inhibition of histone deacetylation enhances the neurotoxicity induced by the C
      terminal fragments of amyloid precursor protein.
AB  - The AICD (APP intracellular Domain) and C31, caspase-cleaved C-terminal fragment
      of APP, have been found in Alzheimer's disease (AD) patients' brains and have
      been reported to induce apoptosis in neuronal cells. In recent, the C-terminal
      fragments of amyloid precursor protein (APP-CTs) have been reported to form a
      complex with Fe65 and the histone acetyltransferase Tip60 and are thought to be
      involved in gene transcription. In this study, based on the hypothesis that APP
      CTs might exert neurotoxicity by inducing some gene transcription, we
      investigated the effects of APP-CTs on histone acetylation which indicates that
      transcription is actively going on and also on the relationship between histone
      acetylation and the cytotoxicity induced by APP-CTs in nerve growth factor (NGF)
      differentiated PC12 cells and rat primary cortical neurons. Here we demonstrate
      that the expression of APP-CTs [C31, AICD (C59) and C99] induces increases in
      acetylation of histone 3 and histone 4 and that treatment with sodium butyrate,
      an inhibitor of histone deacetylase, significantly enhances the cytotoxicity
      induced by APP-CTs. The acetylation of histone plays an important role in
      allowing regulatory proteins to access DNA and is likely to be a major factor in
      the regulation of gene transcription. Taken together, our results suggest that
      APP-CTs exert neurotoxicity by transcription-dependent mechanisms and this might
      contribute to the pathogenesis of AD.

PMID- 14689456
TI  - Influence of hypnogenic brain areas on wakefulness- and rapid-eye-movement sleep
      related neurons in the brainstem of freely moving cats.
AB  - Rapid-eye-movement (REM) sleep is normally preceded by non-REM sleep; however,
      every non-REM sleep episode is not followed by REM sleep. It has been proposed
      that, for the regulation of REM sleep, the brain areas modulating waking and non
      REM sleep are likely to communicate with neurons promoting REM sleep. The former
      has been reported earlier, and in this study the latter has been investigated.
      Under surgical anaesthesia, cats were prepared for electrophysiological recording
      of sleep-wakefulness and electrical stimulation of caudal brainstem as well as
      preopticoanterior hypothalamic hypnogenic areas. Insulated microwires of 25-32
      microm were used to record 52 single neuronal activities from the brainstem along
      with bipolar electroencephalogram, electromyogram, electrooculogram, and
      pontogeniculooccipital waves in freely moving, normally behaving cats. The
      neurons were classified into five groups based on changes in firing rates
      associated with different sleep-waking states compared with quiet wakefulness.
      Thereafter, the responses of these neurons to 1-Hz stimulation of the two non-REM
      sleep-promoting areas were studied. At the end of experiment, the stimulating and
      recording sites were histologically identified. It was observed that, among the
      affected neurons, the caudal brainstem non-REM sleep-promoting area excited more
      REM-on neurons, whereas the preopticoanterior hypothalamus hypnogenic area
      inhibited more awake-active neurons. Thus, the results suggest that, at the
      single neuronal level, the caudal brainstem non-REM sleep-modulating area, rather
      than the preopticoanterior hypothalamic hypnogenic area in the brain, plays a
      modulatory role in triggering REM sleep initiation at a certain depth of sleep.

PMID- 14689455
TI  - Prenatal infection obliterates glutamate-related protection against free hydroxyl
      radicals in neonatal rat brain.
AB  - Prenatal infection constitutes an important risk factor for brain injury, in both
      premature and full-term infants. Unfortunately, as the mechanisms involved are
      far from understood, no therapeutic strategy emerges to prevent the damage. We
      tested the hypothesis that administration of lipopolysaccharide (LPS) to gravid
      female rats enhanced glutamate-induced oxidative stress in brain of pups. A
      microdialysis probe was implanted into the striatum of 14-day-old animals and the
      release of hydroxyl radicals (.OH) in the perfusion medium was evaluated.
      Glutamate promoted a delayed.OH release in the offspring of dams given LPS,
      contrasting with the.OH decreases observed in control animals. A similar response
      occurred after infusion of (R,S)-3,5-dihydroxyphenylglycine (DHPG), a Group I
      metabotropic glutamate receptor (mGluR) agonist. This response was not
      consecutive to a remote activation of N-methyl-D-aspartate (NMDA) receptors, as
      it was unaffected by an NMDA receptor antagonist. Furthermore, the response to
      NMDA itself decreased in the offspring of dams given LPS. Massive amounts of
      DHPG, however, likely internalizing the mGlu receptor, still blunted the response
      to NMDA, as in controls. No quantitative variation occurred in mGluR1, mGluR5, or
      the NR1 subunit of the NMDA receptor between controls and neonates born from LPS
      treated dams. Direct LPS injection into age-matched pups, by contrast, affected
      the response to neither glutamate nor DHPG. These results confirm that normally
      during perinatal development, the brain is protected from any oxidative stress
      resulting from excess glutamate, and the results support the hypothesis that
      maternal infection before delivery may lead to critical brain damage via the
      release of toxic free radicals.

PMID- 14689457
TI  - An immunohistochemical method that distinguishes free from complexed SNAP-25.
AB  - Soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein
      receptor (SNARE) complexes composed of target (t-) SNAREs syntaxin and SNAP-25
      and vesicle SNARE synaptobrevin play an essential role in neurosecretion. It is
      hypothesized that a transient intermediate complex between the t-SNAREs is formed
      during the assembly of the ternary complex. The existence of the t-SNARE binary
      complexes in vivo, however, has not been demonstrated. By using an affinity
      absorption scheme with preformed syntaxin-SNAP-25 complexes, we isolated
      antibodies capable of distinguishing free SNAP-25 from those associated with
      syntaxin. By semiquantitative immunohistochemistry, we estimated that, in
      cultured cerebellar neurons, the majority of SNAP-25 existed as complexes.
      Compared with the cultured neurons, PC12 cells expressed significantly less
      syntaxin, and we found that SNAP-25 was primarily in free forms. In contrast, a
      PC12 line that stably expressed a recombinant syntaxin showed a marked increase
      in SNAP-25 complexes. By using fluorescence resonance energy transfer (FRET)
      techniques, we observed FRET between cyan fluorescence protein-syntaxin and
      yellow fluorescence protein-SNAP-25 fusion proteins expressed in COS-7 and PC12
      cells, suggesting a physiological interaction between syntaxin and SNAP-25. Our
      results demonstrate that, unlike what was previously hypothesized, syntaxin and
      SNAP-25 exist preferably as stable binary complexes in neurons. These findings
      offer novel insight into the mechanisms underlying the initiation and regulation
      of SNARE complex assembly.

PMID- 14689458
TI  - Psychoneuroimmunology in nursing research: a biobehavioral model.

PMID- 14689459
TI  - Multisensory intervention improves physical growth and illness rates in Korean
      orphaned newborn infants.
AB  - The purpose of this study was to evaluate the effectiveness of a multisensory
      intervention on the physical growth and health of Korean orphaned infants. Fifty
      eight full-term infants were randomly assigned to a control (n = 28) or an
      experimental (n = 30) group within 14 days postbirth. In addition to receiving
      the routine orphanage care, infants in the experimental group received 15 min of
      auditory (female voice), tactile (massage), and visual (eye-to-eye contact)
      stimulation twice a day, 5 days a week, for 4 weeks. Compared to the control
      group, the experimental group had gained significantly more weight and had larger
      increases in length and head circumference after the 4-week intervention period
      and at 6 months of age. In addition, the experimental group had significantly
      fewer illnesses and clinic visits. These data demonstrate that multisensory
      intervention in conjunction with human/social contact may be effective in
      facilitating growth for newborn infants placed in orphanages.

PMID- 14689460
TI  - Correlates of fatigue in critical care nurses.
AB  - The purposes of this study were to examine shift-related differences in chronic
      fatigue and the contributions of sleep quality, anxiety, and depression to
      chronic fatigue among a random nationwide sample (N = 142) of female critical
      care nurses. Twenty-three percent of this sample met criteria for clinical
      depression. Day and night nurses did not differ in their reports of chronic
      fatigue. Night nurses reported more depression and poorer sleep quality than did
      day nurses. Regression analyses indicated that among the variables of global
      sleep quality, depression, and anxiety, depression and sleep quality were the
      most relevant to the explanation of chronic fatigue. These findings suggest the
      need for studies of strategies to promote sleep and improve mood in critical care
      nurses.

PMID- 14689461
TI  - Appraisal, coping, hardiness, and self-perceived health in community-dwelling
      spouse caregivers of persons with dementia.
AB  - Although researchers have suggested that hardiness is associated with improved
      outcomes in stressful situations, findings regarding its moderating effects have
      been mixed. Relationships among hardiness, appraisal, coping, self-perceived
      health, and other antecedent variables were examined in a convenience sample of
      72 community-dwelling spouse caregivers for persons with dementia. In this
      descriptive correlational design, participants completed a mailed survey.
      Regression analyses were used to detect main and moderating effects. Antecedent
      variables predicted 27% of the variance in caregiver appraisal, 23% of the
      variance in emotion-focused coping, and 22% of the variance in self-perceived
      health. In addition to its significant main effects, hardiness functioned as a
      significant moderator between the set of antecedent variables and caregiver
      appraisal. More research is needed to support the presence of main and moderating
      effects of hardiness in dementia caregivers.

PMID- 14689462
TI  - Barriers and facilitators of self-reported physical activity in cardiac patients.
AB  - The purpose of this study was to examine the relationships of personal factors
      (age and gender), barriers (symptom distress and negative well-being), and
      facilitators (self-efficacy to exercise and positive well-being) with self
      reported physical activity in cardiac patients. Sixty-four participants (50 men,
      14 women) 6-12 months post-cardiac event participated in this study. We found
      that age and gender accounted for 14.7% of the variance, symptom distress and
      negative well-being accounted for an additional 21.6% of the variance, and self
      efficacy accounted for the remaining 7.6% of the variance for a total of 44% of
      the variance in physical activity levels explained. These results suggest that
      personal factors and barriers are central variables, in addition to self
      efficacy, in understanding the levels of physical activity achieved by patients
      after a cardiac event.

PMID- 14689463
TI  - Motherhood in the context of maternal HIV infection.
AB  - Metasummary and metasynthesis techniques were used to integrate findings
      pertaining to motherhood in 56 reports of qualitative studies conducted with HIV
      positive women. Motherhood in the context of maternal HIV infection entailed work
      directed toward the illness itself and the social consequences of having HIV
      infection in the service of two primary goals: the protection of children from
      HIV infection and HIV-related stigma and the preservation of a positive maternal
      identity. Motherhood both intensified and mitigated the negative physical and
      social effects of HIV infection. HIV-positive mothers engaged in a distinctive
      kind of maternal practice-virtual motherhood-to resist forces that disrupted
      their relationships with and ability to care for their children, as well as their
      identities as mothers.

PMID- 14689464
TI  - Developing risk-adjusted 30-day hospital mortality rates.
AB  - This article describes one risk-adjustment method useful for minimizing threats
      to internal validity that stem from the impact on the outcomes under
      investigation from patients' own characteristics and their associated risks.
      Mortality is the outcome used to illustrate the risk-adjustment approach. A two
      step approach to outcomes research is suggested. The first step includes risk
      adjusting outcomes for patient characteristics by developing standard mortality
      rates. In the second step these risk-adjusted standard rates can be used as
      dependent variables in outcomes analytic models. This article focuses on the
      first step. In the current study risk adjustment resulted in changes in both
      absolute values and rank ordering of hospital mortality rates compared to crude
      rates. This procedure is useful for developing risk-adjusted outcomes with
      administrative data similar to those used in this study.

PMID- 14689465
TI  - Single-point plasma or urine dextromethorphan method for determining CYP3A
      activity.
AB  - Dextromethorphan is used widely in vivo to phenotype the polymorphically
      expressed cytochrome P450 (CYP) 2D6. Also dextromethorphan is N-demethylated in
      vivo to 3-methoxymorphinan by human CYP3A4/5. The metabolic ratio (MR) of
      dextromethorphan/3-methoxymorphinan in plasma, saliva and urinary were examined
      as a possible in vivo probe of CYP3A activity. In limited previous studies, 4 h
      urinary samples were collected for determining the MR. To evaluate the
      repeatability and validity of previously reported and other potential phenotyping
      methods, the MR from urine samples (at various intervals), from plasma and from
      saliva (at varying time points) were determined after repetitive single doses of
      immediate-release or repetitive multiple doses of controlled-release
      dextromethorphan preparations. For the single-dose study, each of 12 subjects
      received 15 mg of immediate-release dextromethorphan in periods II and I,
      respectively, with a 1 week washout period. For the multiple dose study, each of
      16 subjects received 60 mg controlled release dextromethorphan twice daily for 5
      days in periods I and II, respectively, with a 2 week washout period.
      Dextromethorphan and 3-methoxymorphinan are assayed by high-performance liquid
      chromatography. In the single-dose study, all of the urine MR revealed good
      repeatabilities for the periods (paired t-test). The urine MR at any time
      interval of 0-6 h, 0-8 h and 0-12 h correlated significantly with the MR from 0
      24 h urine (r>0.8, p<0.05). In the multiple-dose study, all MR revealed good
      repeatabilities for the two periods (paired t-test). The plasma MR at any time
      between 0.5 h and 12 h, the saliva MR at 12 h and the urine MR at any interval
      between 0-2 h, 0-4 h, 0-6 h, 0-8 h, 0-12 h and 0-24 h could predict the MR from
      AUCtau(ss). In conclusion, the urine sample as 0-6 h, 0-8 h or 0-12 h in the
      single immediate-release dose (15 mg) or in the multiple controlled-release dose
      (60 mg) procedure, the saliva sample at 12 h, the urine sample at 0-2 h, 0-4 h, 0
      6 h, 0-8 h, 0-12 h, 0-24 h or all plasma-sampling points 0.5-12 h could be used
      as the dextromethorphan MR for determining the CYP3A activity.

PMID- 14689466
TI  - Rapid determination of enzyme activities of recombinant human cytochromes P450,
      human liver microsomes and hepatocytes.
AB  - Cytochrome P450 (CYP) substrates that yield fluorescent metabolites were used for
      rapid screening of drug metabolism activities of 13 recombinant human cytochromes
      P450, human liver microsomes and human hepatocytes. Reproducible results were
      obtained using a fluorescent plate reader (CytoFluor) more expediently than those
      generated using conventional HPLC methods. Typically, results for 96 samples were
      obtained with the plate reader in less than 10 min as opposed to 15-35 min/sample
      required by conventional HPLC. The fluorescent substrates used to measure CYP
      activities were as follows: 3-cyano-7-ethoxycoumarin (CEC) for CYP1A1, CYP1A2,
      CYP2C9 and CYP2C19; 7-ethoxyresorufin (7-ER) for CYP1A1, CYP1A2 and CYP1B1; 3-[2
      (N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin (AMMC) for
      CYP2D6; dibenzylfluorescein (DBF) for CYP3A4, CYP3A5 and CYP2C8; 7-methoxy-4
      trifluoromethylcoumarin (7-MFC) for CYP2E1, CYP2B6 and CYP2C18; and coumarin for
      CYP2A6. The chemical inhibition and correlation data indicated that the following
      substrates can be used as specific functional probes for individual cytochrome
      P450 present in human liver microsomes: coumarin for CYP2A6 (r=0.82), AMMC for
      CYP2D6 (r=0.83) and DBF for CYP3A4 (r=0.92). The fluorescent plate reader was
      found to be useful for the rapid assessment of CYP activities (positive control)
      in both intact cells and subcellular fractions.

PMID- 14689467
TI  - Dose-dependent pharmacokinetics of 1-(2-deoxy-beta-D- ribofuranosyl)-2,4-difluoro
      5-iodobenzene: a potential mimic of 5-iodo-2'-deoxyuridine.
AB  - The dose-range pharmacokinetics of l-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluoro
      5-iodobenzene (5-IDFPdR), a C-aryl nucleoside mimic of IUdR, were studied in male
      Sprague-Dawley rats following single intravenous (i.v.) and oral doses. After
      i.v. administration, the blood clearance decreased from approximately 32
      ml/min/kg at a dose of 15 mg/kg, to approximately 19 ml/min/kg when dosed at 54
      mg/kg, and the elimination half-life increased from 8.4 min to 21.5 min, for the
      respective doses. While the dose-normalized area under the concentration-time
      curve (AUCnorm) remained practically unchanged (0.132 kg min ml(-1)) upon
      increasing the i.v. dose from 5 to 15 mg/kg, it increased by about 44% (
      approximately 0.19 kg min ml(-1)) when the i.v. dose was increased from 15 to 54
      mg/kg. Similarly, there was a dose-dependent increase in AUCnorm with increasing
      oral doses: AUCnorm increased by 49% as the oral dose increased from 20 to 40
      mg/kg, and further by 55% as the oral dose was increased from 40 mg/kg to 54
      mg/kg. For the respective oral doses, the elimination half-life increased from
      24.5 min to 176 min, while blood clearance was reduced from approximately 37
      ml/min/kg to approximately 17 ml/min/kg. The urinary recoveries of unchanged 5
      IDFPdR and its glucuronides (as percent of the dose) were somewhat increased at
      higher doses. This increase was more pronounced following the highest oral dose.
      The total biliary recovery of 5-IDFPdR (as percent of the dose) was, however,
      decreased with increasing doses. The overall kinetic profile of 5-IDFPdR based on
      these data is suggestive of dose-dependent pharmacokinetics. Decreased
      elimination of 5-IDFPdR with increasing dose, as supported by longer elimination
      half-lives at higher doses, is one likely mechanism contributing to the dose
      dependent behaviour of this compound. Saturable non-renal metabolism might
      explain the reduced total body clearance of 5-IDFPdR at higher doses, despite the
      unchanged or increased urinary clearance. For drugs exhibiting nonlinear
      kinetics, the dosage regimens may need to be carefully designed to avoid
      potential unpredictable toxicity and/or lack of pharmacological response
      associated with the disproportional changes in steady state drug concentrations
      on changing dose. Manifestation in the rat of nonlinear kinetics at doses of 5
      IDFPdR, which may be of therapeutic relevance, warrants extended dose-range
      evaluations of this compound in future preclinical and clinical studies, to
      establish safe and efficacious dosage regimens.

PMID- 14689468
TI  - Preclinical evaluation of the pharmacokinetics, brain uptake and metabolism of
      E121, an antiepileptic enaminone ester, in rats.
AB  - The present study describes the brain uptake, pharmacokinetics and metabolism of
      an anticonvulsant enaminone ester E121, which belongs to a new and active series
      of compounds with potential in vivo anticonvulsant activity in rodent models, in
      rats. A single dose of E121 was administered i.p. to male Sprague Dawley rats at
      10 mg E121/kg body weight. Cohorts of animals (n=3) were killed at varying times
      over 0-24 h to collect plasma and brain samples. Urinary excretion of E121 was
      studied in a separate group of five rats at the same dose. A validated HPLC
      method was used to quantify E121 and its metabolites in plasma, brain and urine.
      LC-MS/MS was used to characterize the metabolites. The plasma and brain Cmax of
      11.0+/-3.0 mg/l and 10.4+/-1.4 mg/kg, respectively, were observed for E121 at 15
      min post dose and they declined in a mono-exponential fashion. The plasma Cl/F
      and t1/2 were 0.57 l/h/kg and 0.75 h, respectively. The brain uptake ratio of
      E121 was 0.9. Mass spectral analysis of urine showed two major metabolites (m/z
      280) and one minor metabolite (m/z 236) that were consistent with initial
      hydrolysis of the compound to the acid followed by further decarboxylation and
      appears to be the major route of elimination of E121. The rapid and moderate
      brain uptake of E121 correlates well with its potential anticonvulsant activity
      (ED50 3.0 mg/kg p.o. in rats). The brain uptake, pharmacokinetic and metabolic
      profile of E121 supports the need to further evaluate this compound for its
      potential as an antiepileptic.

PMID- 14689469
TI  - Subacute toxicities and toxicokinetics of DA-8159, a new phosphodiesterase type V
      inhibitor, after single and 4-week repeated oral administration in rats.
AB  - The subacute toxicities (10 male and 10 female rats at each dose) and the
      toxicokinetics (5 male rats at each dose) of DA-8159, a new phosphodiesterase
      type V (PDE V) inhibitor, were evaluated after single (at day 1) and 4-week (at
      day 28) oral administration of the drug at doses of 0 (to serve as a control),
      20, 80 and 320 mg/kg/day to rats. DA-8159 showed a decrease in body weight gain,
      clinical signs such as chromodacryohaemorrhoea, ptosis and decreased locomotor
      activity, an increase in WBC number, changes in parameters related to RBCs, an
      increase in organ weight of the liver, spleen and lung, and finally microscopic
      lesions such as cholangiofibrosis and inflammatory cell infiltration in the
      liver, alveolar macrophage accumulation, and inflammatory cell infiltration in
      the lung, an increase in bone marrow density and extrahaematopoiesis in the
      spleen. These changes were observed mainly at a dose of 80 mg/kg or above. While
      some changes were observed at a dose of 20 mg/kg, these changes were non-specific
      and transient since this were also observed in control rats. In addition, there
      was no dose-dependency in these changes. Based on these results, the NOAEL (No
      Observed-Adverse-Effect-Level) for DA-8159 in rats was estimated to be 20
      mg/kg/day, and the target organs were determined to be liver, bone marrow,
      spleen, lung and blood cells. After a 4-week oral administration, accumulation of
      DA-8159 was evident at a dose of 20 mg/kg/day, but was not considerable at toxic
      doses (80 and 320 mg/kg/day). After a single oral administration, the dose
      normalized area under the plasma concentration-time curve from time zero to the
      last measured time, 24 h, in plasma (AUC(0-24 h)) was significantly different
      among the three doses (the AUC(0-24 h) based on 20 mg/kg/day was 2.33, 7.00 and
      4.19 microg h/ml for 20, 80 and 320 mg/kg/day, respectively). Similar results
      were also obtained from DA-8164, a metabolite of DA-8159; the AUC(0-24 h) of DA
      8164 after dose-normalized to 20 mg/kg/day of DA-8159 were 2.74, 5.00 and 1.68
      microg h/ml, respectively.

PMID- 14689470
TI  - Mechanical stimulation releases nucleotides that activate P2Y1 receptors to
      trigger neural reflex chloride secretion in guinea pig distal colon.
AB  - Stroking the mucosal lining of the guinea pig colon with a brush elicits an
      intestinal neural reflex, and an increase in short-circuit current (Isc)
      indicative of chloride secretion. We tested whether endogenous and exogenous
      nucleotides are physiologic regulators of mucosal reflexes that modulate chloride
      secretion. The basal Isc was augmented by 6-N,N-diethyl-beta,gamma
      dibromomethylene-D-adenosine-5'-triphosphate (ARL67156) inhibition of nucleotide
      breakdown or adenosine A1 receptor blockade and reduced by apyrase inactivation
      of nucleotidases, P2 receptor antagonists, tetrodotoxin (TTX), or piroxicam.
      ARL67156 augmented, and apyrase inhibited, stroking-evoked Isc responses. TTX and
      atropine inhibited nucleotide-evoked Isc responses. The agonist potency profile
      for Isc, 2-methylthioadenosine-diphosphate (2MeSADP) = 2-methioadenosine
      triphosphate >> 5'adenosine-triphosphate (ATP) > or = 5'adenosine-diphosphate >
      5'uridine-triphosphate > or = 5'uridine-diphosphate, supports a P2Y1 receptor
      (R). The P2 receptor antagonists suramin and pyridoxalphosphate-6-azophenyl-2'4'
      disulfonic acid, reduced stroking responses (36%) and their effects were
      additive. The selective P2Y1 R antagonist, 2'deoxy-N6-methyl adenosine 3',5'
      diphosphate diammonium salt, reduced stroking (54%) and 2MeSADP (70%) responses
      at P2Y1 Rs. The P2X1/3 R agonist, alpha,betaMeATP, increased Isc. A desensitizing
      dose of alpha,betaMeATP reduced stroking Isc responses but did not prevent the
      2MeSADP-evoked Isc response. Reverse transcriptase polymerase chain reaction
      analysis revealed mRNAs for P2Y1 R, P2Y2 R, P2Y4 R, P2Y6 R, and P2Y12 R in
      submucosa. The expression of P2Y R immunoreactivity (ir) in cell bodies of
      submucous neurons followed the order of P2Y1 = P2Y2 >> P2Y4 R ir; P2Y1 Rs and
      P2Y2 R ir were abundant (21-50% of neurons). P2Y1 R ir was abundant in
      cholinergic secretomotor neurons and fewer than 2% of neuropeptide Y
      (NPY)/choline acetyltransferase secretomotor neurons, and P2Y2 R ir was expressed
      in virtually all NPY secretomotor neurons and approximately 30% of
      calbindin/intrinsic primary afferent neurons. P2Y4 R ir was present in NPY
      positive neurons. P2Y ir was rare or absent in varicose nerve fibers. The
      functional data support the hypothesis that mechanical stimulation with a brush
      releases nucleotides that act predominantly at P2Y1 Rs and to a lesser extent on
      P2X1/3 Rs to mediate reflex chloride secretion. A separate P2Y2 R neural circuit
      pathway exists that is not activated by mechanical forces. Other receptors
      including P2Y4, P2Y6, P2Y12, or P4 Rs cannot be excluded.

PMID- 14689471
TI  - Mechanically evoked reflex electrogenic chloride secretion in rat distal colon is
      triggered by endogenous nucleotides acting at P2Y1, P2Y2, and P2Y4 receptors.
AB  - Mechanical activation of the mucosal lining of the colon by brush stroking
      elicits an intestinal neural reflex and an increase in short circuit current
      (Isc) indicative of electrogenic chloride ion transport. We tested whether
      endogenous nucleotides are physiologic regulators of mucosal reflexes that
      control ion transport. The brush stroking-evoked Isc response in mucosa and
      submucosa preparations (M-SMP) of rat colon was reduced by the P2Y1 receptor (R)
      antagonist 2'deoxy-N6-methyl adenosine 3',5'-diphosphate diammonium salt (MRS
      2179) and further blocked by tetrodotoxin (TTX). M-SMP Isc responses to serosal
      application of the P2Y1 R agonist 2-methylthioadenosine-diphosphate (2MeSADP) or
      the P2Y2/P2Y4 R agonist 5'uridine-triphosphate (UTP) were reduced but not
      abolished by TTX. The potency profile of nucleotides for increasing Isc was
      5'adenosine-triphosphate (ATP; effective concentration at half maximal response
      [EC50] 0.65 x 10(4) M) congruent with UTP (EC50 1.0 x 10(-4) M) congruent with
      2MeSADP (EC50 = 1.60 x 10(-4) M). Mucosal touch and distention-induced Ca2+
      transients in submucous neurons were reduced by apyrase and prevented by blocking
      the P2Y1 R with MRS 2179 and TTX; denervation of the mucosa. It did not occur by
      touching a ganglion directly. 2MeSADP Ca2+ responses occurred in subsets of
      neurons with or without substance P (SP) responses. The potency profile of
      nucleotides on the neural Ca2+ response was 2MeSADP (5 x 10(-7) M) > UTP (6 x 10(
      6) M) > ATP (9 x 10(-5) M). The expression of P2Y R immunoreactivity (ir) in
      nerve cell bodies was in the order of P2Y1 R > P2Y4 R >> P2Y2 R. P2Y1R ir
      occurred in the cell somas of more than 90% of neuronal nitric oxide synthase,
      vasoactive intestinal peptide (VIP), calretinin, or neuropeptide Y (NPY)-ir
      neurons, 78% of somatostatin neurons, but not in calbindin or SP neurons. P2Y2 R
      ir was expressed in a minority of SP, VIP, NPY, vesicular acetylcholine
      transporter, and calcitonin gene-related peptide-ir varicose fibers (5-20%) and
      those surrounding calbindin (5-20%) neurons. P2Y4 ir occurred mainly in the cell
      somas of 93% of NPY neurons. Reverse transcriptase polymerase chain reaction of
      the submucosa demonstrated mRNA for P2Y1R, P2Y2, P2Y4, P2Y6, and P2Y12 Rs.
      Expression of P2Y1, P2Y2, and P2Y4 protein was confirmed by western blots. In
      conclusion, endogenous nucleotides acting at P2YRs transduce mechanically evoked
      reflex chloride ion transport in rat distal colon. Nucleotides evoke reflexes by
      acting primarily at postsynaptic P2Y1 Rs and P2Y4 R on VIP+/NPY+ secretomotor
      neurons, at P2Y2 Rs on no more than 2% of VIP+ secretomotor neurons, and 2Y2 Rs
      mainly of extrinsic varicose fibers surrounding putative intrinsic primary
      afferent and secretomotor neurons. During mucosal mechanical reflexes, it is
      postulated that P2Y1 R, P2Y2 R, and P2Y4 R are activated by endogenous ATP, UTP,
      and 5'uridine-diphosphate.

PMID- 14689472
TI  - Cytoarchitecture and cortical connections of the posterior cingulate and adjacent
      somatosensory fields in the rhesus monkey.
AB  - The cytoarchitecture and connections of the caudal cingulate and medial
      somatosensory areas were investigated in the rhesus monkey. There is a stepwise
      laminar differentiation starting from retrosplenial area 30 towards the
      isocortical regions of the medial parietal cortex. This includes a gradational
      emphasis on supragranular laminar organization and general reduction of the
      infragranular neurons as one proceeds from area 30 toward the medial parietal
      regions, including areas 3, 1, 2, 5, 31, and the supplementary sensory area
      (SSA). This trend includes a progressive increase in layer IV neurons. Area 23c
      in the lower bank and transitional somatosensory area (TSA) in the upper bank of
      the cingulate sulcus appear as nodal points. From area 23c and TSA the
      architectonic progression can be traced in three directions: one culminates in
      areas 3a and 3b (core line), the second in areas 1, 2, and 5 (belt line), and the
      third in areas 31 and SSA (root line). These architectonic gradients are
      reflected in the connections of these regions. Thus, cingulate areas (30, 23a,
      and 23b) are connected with area 23c and TSA on the one hand and have widespread
      connections with parieto-temporal, frontal, and parahippocampal (limbic) regions
      on the other. Area 23c has connections with areas 30, 23a and b, and TSA as well
      as with medial somatosensory areas 3, 1, 2, 5, and SSA. Area 23c also has
      connections with parietotemporal, frontal, and limbic areas similar to areas 30,
      23a, and 23b. Area TSA, like area 23c, has connections with areas 3, 1, 2, 5, and
      SSA. However, it has only limited connections with the parietotemporal and
      frontal regions and none with the parahippocampal gyrus. Medial area 3 is mainly
      connected to medial and dorsal sensory areas 3, 1, 2, 5, and SSA and to areas 4
      and 6 as well as to supplementary (M2 or area 6m), rostral cingulate (M3 or areas
      24c and d), and caudal cingulate (M4 or areas 23c and d) motor cortices. Thus, in
      parallel with the architectonic gradient of laminar differentiation, there is
      also a progressive shift in the pattern of corticocortical connections. Cingulate
      areas have widespread connections with limbic, parietotemporal, and frontal
      association areas, whereas parietal area 3 has more restricted connections with
      adjacent somatosensory and motor cortices. TSA is primarily related to the
      somatosensory-motor areas and has limited connections with the parietotemporal
      and frontal association cortices.

PMID- 14689473
TI  - Types of bipolar cells in the mouse retina.
AB  - We studied the morphology of bipolar cells in fixed vertical tissue sections
      (slices) of the mouse retina by injecting the cells with Lucifer Yellow and
      Neurobiotin. Nine different cone bipolar cell types and one rod bipolar cell type
      were distinguished. The major criteria for classifying the cells were the
      branching pattern and stratification level of their axon terminals in the inner
      plexiform layer (IPL). To assess this, the IPL was subdivided into five strata of
      equal width. The slices were immunostained for calretinin, which labels three
      horizontal bands serving as a standard measure for the precise localization of
      the axon terminals. Immunostaining the retina with antibodies against the G
      protein Ggamma13, a marker for ON-bipolar cells, made it possible to separate OFF
      and ON-bipolar cells. At least two OFF-cone bipolar cells (Types 1 and 2) were
      immunolabeled with antibodies against the neurokinin 3 receptors (NK3R). A
      further OFF- and an ON-cone bipolar cell (Types 3 and 5) were immunostained with
      antibodies against the calcium-binding protein CaB5. The bipolar cell types
      described here were compared with previous schemes of rat and primate bipolar
      cells. Homologous types between the three species are discussed.

PMID- 14689474
TI  - Parasympathetic nerve fibers invade the upper dermis following sensory
      denervation of the rat lower lip skin.
AB  - The sympathetic division of the autonomic nervous system is known to play a role
      in the genesis of neuropathic pain. In the skin of the rat lower lip (hairy
      skin), sympathetic and parasympathetic fibers normally innervate the same blood
      vessels in the lower dermis but do not occur in the upper dermis. However, we
      have shown that sympathetic fiber migration into the upper dermis occurs
      following mental nerve lesions (Ruocco et al. [2000] J. Comp. Neurol. 422:287
      296). As sensory denervation has a dramatic effect on sympathetic fiber
      innervation patterns in the rat lower lip skin, we decided to investigate the
      possible changes in the other autonomic fiber type in the skin-the
      parasympathetic fiber. Sensory denervation of the rat lower lip was achieved by
      bilateral transection of the mental nerve, and animals were allowed to recover
      for 1-8 weeks. Lower lip tissue was processed for double-labeling light
      microscopic immunocytochemistry (ICC), using antibodies against substance P (SP),
      which labels a subpopulation of peptidergic sensory fibers, and against the
      vesicular acetycholine transporter (VAChT), as a marker for parasympathetic
      fibers. In sham-operated rats, SP-immunoreactive (IR) sensory fibers were found
      in the epidermis and upper and lower dermal regions, whereas VAChT-IR fibers were
      confined to the lower dermis. Mental nerve lesions induced the gradual
      disappearance of SP-IR fibers from all skin layers accompanied by the progressive
      migration of VAChT-IR fibers into the upper dermis. Cholinergic fiber migration
      was evident by the second week post surgery, and the ectopic innervation of the
      upper dermis by these fibers persisted even at the last time point studied (8
      weeks) when SP-IR fibers have completely regrown. VAChT-IR fibers were observed
      in the upper dermis, well above the opening of the sebaceous glands into the hair
      follicles. These results show that considerable changes occur in the innervation
      patterns of parasympathetic fibers following mental nerve lesions.

PMID- 14689475
TI  - Testosterone manipulation protects motoneurons from dendritic atrophy after
      contralateral motoneuron depletion.
AB  - Dendritic morphology is reactive to many kinds of injuries, including axotomy and
      deafferentation. In this study, we examined the response of motoneurons in the
      spinal nucleus of the bulbocavernosus (SNB), an androgen-dependent population of
      motoneurons in the lumbar spinal cord of the rat, to partial motoneuron
      depletion. We depleted SNB motoneurons on one side only of the spinal cord by
      unilateral intramuscular injection of a retrogradely transported form of saporin,
      and examined the morphology of contralateral SNB motoneurons. Motoneuron
      morphology was assessed in normal control males, gonadally intact saporin-treated
      males, and saporin-treated males who had been castrated 6 weeks previously and
      given testosterone replacement beginning at the time of saporin injection.
      Untreated castrated males served as an additional control group. Four weeks after
      saporin treatment, SNB motoneurons contralateral to the saporin injection were
      retrogradely labeled with horseradish peroxidase conjugated to the cholera toxin
      B subunit and reconstructed in three dimensions. In gonadally intact males,
      unilateral motoneuron depletion caused regressive changes in contralateral SNB
      motoneurons: Soma size and dendritic length were both decreased. However,
      testosterone manipulation (i.e., castration followed by testosterone replacement)
      completely prevented the dendritic retraction. These data suggest a therapeutic
      role for testosterone in preventing, or accelerating recovery from, dendritic
      atrophy induced by motoneuron injury.

PMID- 14689476
TI  - Neuronal types expressing mu- and delta-opioid receptor mRNA in the rat
      hippocampal formation.
AB  - Opioids are thought to control the excitability of hippocampal principal neurons
      indirectly by inhibiting GABAergic interneurons. However, direct inhibition of
      hippocampal principal neurons by opioids has also been reported. To understand
      better the neuromodulatory role of opioids in rat hippocampal circuits, we
      analyzed types of micro- and delta-opioid receptor (MOR, DOR)-expressing
      hippocampal neurons. Most MOR-immunoreactive neurons in the granular and
      pyramidal cell layers exhibited multipolar morphologies characteristic of
      GABAergic neurons. Virtually all neurons in the hippocampal formation expressing
      high MOR mRNA levels cocontained the mRNA for glutamic acid decarboxylase (GAD).
      Most parvalbumin-, several calretinin-, and several pre-proenkephalin-containing
      neurons expressed the MOR gene in the hippocampal formation. Expression of high
      DOR mRNA levels was restricted to GAD-positive neurons in the principal cell
      layers, oriens layer and hilus. More than 90% of the parvalbumin-positive neurons
      in the hippocampal formation strongly expressed the DOR gene. Granule cells
      expressing vesicular glutamate transporter 1 (VGLUT1) mRNA contained very low MOR
      and DOR transcript levels. In VGLUT1-positive pyramidal cells, weak DOR but no
      MOR gene expression was detected. Whereas most somatostatinergic hilar neurons
      were negative for MOR and DOR mRNA, somatostatinergic oriens layer neurons
      frequently expressed these receptors. Taken together, weak expression of MOR and
      DOR genes in hippocampal principal cells is in concordance with direct opioid
      mediated inhibition of principal cells. However, strong expression of the MOR and
      DOR genes in the hippocampus is restricted to gamma-aminobutyric acid (GABA)ergic
      neurons, with DORs being selectively expressed in the parvalbumin- and
      somatostatin-containing subpopulations. Activation of MOR and/or DOR in
      parvalbumin- and somatostatin-containing neurons, which provide GABAergic
      inhibition to the perisomatic and distal dendritic regions of principal cells,
      respectively, is likely to facilitate principal cell excitation.

PMID- 14689477
TI  - Compartmentation of the mouse cerebellar cortex by sphingosine kinase.
AB  - Classic cerebellar anatomy is based on the characteristic array of lobes and
      lobules. However, there is substantial evidence to suggest that more fundamental
      architecture is built around arrays of parasagittal stripes, which encompass both
      the inputs and outputs of the Purkinje cells (PCs). Sphingosine kinase (SPHK) is
      an enzyme that converts sphingosine (Sph) into sphingosine-1-phosphate (S1P).
      Recent reports have indicated that ceramide, Sph, and S1P play a role in cell
      survival, growth, and differentiation in several cell types, including neurons.
      In this study, we examined the localization of SPHK in the mouse cerebellum by
      using immunohistochemistry. Anti-SPHK immunoreactivity appeared in the cerebellar
      molecular layer and the PC membranes. The staining pattern is striped. In the
      molecular layer, the staining pattern probably reflects dendritic spines and
      dendrites. By electron microscopy, peroxidase reaction product was deposited
      within dendrites especially along the plasma membranes near spines. Seen at
      higher magnification, the staining was in and near the postsynaptic complexes. By
      double immunostaining, the striped pattern of SPHK expression was shown to be
      identical to that revealed by anti-zebrin II, although the subcellular
      distribution within PC's is not. This is the first demonstration of the
      cerebellar compartmentation of an enzyme related to lipid metabolism, and as
      such, it provides an insight into the roles of SPHK and formation of S1P. The
      selective expression of SPHK in the zebrin II-immunoreactive PCs may explain
      their resistance to cell death when ceramide metabolism is disrupted, as in the
      acid sphingomyelinase knockout model of Niemann-Pick type A/B disease.

PMID- 14689478
TI  - Unique expression patterns of 5-HT2A and 5-HT2C receptors in the rat brain during
      postnatal development: Western blot and immunohistochemical analyses.
AB  - Serotonin (5-HT) is recognized as a potential regulatory factor in neuronal
      development. Two subtypes of receptors for it, 5-HT2A and 5-HT2C, are distributed
      broadly in the rat brain, suggesting their role in a variety of brain functions.
      Here, we investigated the expression patterns of these 5-HT2 receptors in the rat
      brain during postnatal development by using Western blot and immunohistochemical
      analyses. By Western blot analysis, the expression of the 5-HT2A receptor was at
      a low level at postnatal day 3 (P3) and increased greatly during the first 3
      postnatal weeks; whereas the 5-HT2C receptor was already expressed at a high
      level at P3, and its expression increased only slightly during postnatal
      development. Immunohistochemical analysis showed the different expression
      patterns of 5-HT2A and 5-HT2C receptor subtypes during postnatal development: the
      transient expression of the 5-HT2C receptor was observed in layer IV of the
      somatosensory, visual, and auditory cortices from P10 to P28, and in the
      thalamus, mainly in the ventral posterolateral and ventral posteromedial nuclei,
      from P7 to P21; however, the immunoreactivity of the 5-HT2A receptor was
      detectable slightly at P3, but thereafter the intensity of immunolabeling
      increased with postnatal development and at P21 reached the adult level and
      pattern. These results suggest that 5-HT2 receptors have potential significance
      in brain development, with a functional difference between 5-HT2A and 5-HT2C
      receptor subtypes.

PMID- 14689479
TI  - Copper/zinc superoxide dismutase-like immunoreactivity in the metamorphosing
      brain of the sphinx moth Manduca sexta.
AB  - Cu/Zn superoxide dismutase (SOD) is part of the defense mechanism that protects
      cells from being damaged by reactive oxygen species. During metamorphosis of the
      nervous system, neurons undergo various fates, which are all coupled to high
      metabolic activities, such as proliferation, differentiation, pathfinding, and
      synaptogenesis. We describe the pattern of SOD immunoreactivity of identified
      neurons and neuron groups in the brain of Manduca sexta from the late larva
      through metamorphosis into adult. We focused on neurons of the developing
      antennal lobes, the optic lobes, and the central brain. Our results indicate the
      transient expression of SOD during phases in which the neurons develop their
      final adult identities. Our data also suggest that the SOD immunoreactivity may
      be used as an indicator for the period in which developing neurons form their
      synapses. We also observed SOD immunoreactivity within nitric oxide-sensitive
      cells as characterized by immunolabeling against 3'5'-cyclic guanosine
      monophosphate and soluble guanylyl cyclase, a novel finding in insects.

PMID- 14689480
TI  - Dynamic expression patterns of Robo (Robo1 and Robo2) in the developing murine
      central nervous system.
AB  - The Robo family of molecules is important for axon guidance across the midline
      during central nervous system (CNS) development in invertebrates and vertebrates.
      Here we describe the patterns of Robo protein expression in the developing mouse
      CNS from embryonic day (E) 9.5 to postnatal day (P) 4, as determined by
      immunohistochemical labeling with an antibody (S3) raised against a common
      epitope present in the Robo ectodomain of Robos 1 and 2. In the spinal cord,
      midline-crossing axons are initially (at E11) S3-positive. At later times,
      midline Robo expression disappears, but is strongly upregulated in longitudinally
      running postcrossing axons. It is also strongly expressed in noncrossing
      longitudinal axons. Differential expression of Robo along axons was also found in
      axons cultured from E14 spinal cord. These findings resemble those from the
      Drosophila ventral nerve cord and indicate that in vertebrates a low level of
      Robo expression occurs in the initial crossing of the midline, while a high level
      of expression in the postcrossing fibers prevents recrossing. Likewise, Robo
      positive ipsilateral axons are prevented from crossing at all. However, in the
      brain different rules appear to apply. Most commissural axons including those of
      the corpus callosum are strongly S3-positive along their whole length from their
      time of formation to postnatal life, but some have more complex age-dependent
      expression patterns. S3 labeling of the optic pathway is also complex, being
      initially strong in the retinal ganglion cells, optic tract, and chiasma but
      thereafter being lost except in a proportion of postchiasmal axons. The
      corticospinal tract is strongly positive throughout its course at all stages
      examined, including its decussation, formed at about P2 in the central part of
      the medulla oblongata.

PMID- 14689481
TI  - Evidence for a glutamatergic projection from the zona incerta to the basal
      ganglia of rats.
AB  - This study explores the organisation and neurochemical nature of the projections
      from the zona incerta (ZI) to the basal ganglia. Sprague-Dawley rats were
      anaesthetised with ketamine (100 mg/kg) and Rompun (10 mg/kg), and injections of
      cholera toxin subunit B were made into each of the following nuclei: the ZI, the
      substantia nigra (SN), the pedunculopontine tegmental nucleus (PpT), and the
      entopeduncular nucleus (Ep). Brains were aldehyde fixed, sectioned, and processed
      using standard methods. Tracer-labelled sections were then doubly labelled with
      antibodies to glutamate (Glu), nitric oxide synthase (NOS), parvalbumin (Pv), or
      glutamic acid decarboxylase (GAD; the latter two are markers for GABAergic
      cells); these neurochemicals characterise most types of ZI cells. After ZI
      injections, labelling was nonuniform across the different basal ganglia nuclei.
      The bulk of labelling, both anterograde and retrograde, was seen in the SN and
      PpT and, to a lesser extent, within the other nuclei of the basal ganglia (e.g.,
      caudate-putamen, globus pallidus, subthalamus, Ep). In the SN, labelling was
      found in both major parts of the nucleus, the pars compacta and pars reticulata.
      Within the PpT, however, the bulk of labelling was limited to only one of the two
      sectors of the nucleus, namely, the pars dissipata (PpTd). The pars compacta of
      the PpT (PpTc) remained largely free of labelled profiles. After CTb injections
      into three basal ganglia nuclei (SN, PpT, Ep), most labelled cells in the ZI were
      glutamate+ and very few were NOS+ or gamma-aminobutyric acidergic. Overall, the
      results indicate that the ZI is in a position to influence preferentially the
      activity of the SN and PpTd of the basal ganglia via an excitatory, glutamatergic
      input.

PMID- 14689482
TI  - Expression of axonin-1 in developing amacrine cells in the chick retina.
AB  - This study focused on the temporal and spatial pattern of expression of the cell
      adhesion molecule axonin-1 in amacrine cells and the identification of these
      cells in the developing chick retina. We analyzed 5-20-day-old chick embryos. The
      antigen was localized and visualized by the indirect immunogold and the
      immunofluorescence technique. Colocalization studies with antibodies against
      tyrosine hydroxylase, acetylcholinesterase, choline acetyltransferase,
      parvalbumin, calbindin, and calretinin served to characterize these cells further
      and to explore whether they have other properties in common. Axonin-1 was
      expressed in amacrine cells from E8 onward in the inner nuclear, in the inner
      plexiform, and in the ganglion cell layer. Their maturation showed a gradient
      similar to that found for amacrinogenesis. Expression was closely correlated with
      the period when the cells develop and shape their processes. The interneurons
      were classified with reference to Cajal, and most of the morphological types
      described by him were found. In addition, some cells were considered as axon
      bearing amacrine cells. However, the total number of labeled cells was rather
      small. At least two morphologically different types terminated in each of the
      inner plexiform sublayers. Narrow- and wide-field arbors indicated the existence
      of a diversified network. The colocalization studies revealed that the
      neurotransmitters and neuropeptides overlapped partially with axonin-1
      expression. This indicated that axonin-1-immunoreactive amacrine cells were also
      functionally diverse.

PMID- 14689483
TI  - Preservation of hippocampal neuron numbers and hippocampal subfield volumes in
      behaviorally characterized aged tree shrews.
AB  - Aging is associated with a decreased ability to store and retrieve information.
      The hippocampal formation plays a critical role in such memory processes, and its
      integrity is affected during normal aging. We used tree shrews (Tupaia belangeri)
      as an animal model of aging, because in many characteristics, tree shrews are
      closer to primates than they are to rodents. Young and aged male tree shrews
      performed a holeboard spatial memory task, which permits assessment of reference
      and working memory. Upon completion of the behavioral measurements, we carried
      out modified stereological analyses of neuronal numbers in various subdivisions
      of the hippocampus and used the Cavalieri method to calculate the volumes of
      these subfields. Results showed that the working memory of aged tree shrews was
      significantly impaired compared with that of young animals, whereas the
      hippocampus-dependent reference memory remained unchanged by aging. Estimation of
      the number of neurons revealed preserved neuron numbers in the subiculum, in the
      subregions CA1, CA2, CA3, and in the hilus of the dentate gyrus. Volume
      measurements showed no aging-related changes in the volume of any of these
      hippocampal subregions, or in the molecular and granule cell layers of the
      dentate gyrus of tree shrews. We conclude that the observed changes in memory
      performance in aging tree shrews are not accompanied by observable reductions of
      hippocampal neuron numbers or hippocampal volume, rather, the changes in memory
      performance are more likely the result of modified subcellular mechanisms that
      are affected by the aging process.

PMID- 14689484
TI  - Prefrontal cortical projections to the rat dorsal raphe nucleus: ultrastructural
      features and associations with serotonin and gamma-aminobutyric acid neurons.
AB  - Studies of human brain indicate that both the ventromedial prefrontal cortex
      (PFC) and the dorsal raphe nucleus (DRN) may be dysfunctional in major depressive
      illness, making it important to understand the functional interactions between
      these brain regions. Anatomical studies have shown that the PFC projects to the
      DRN, although the synaptic targets of this excitatory pathway have not yet been
      identified. Electrophysiological investigations in the rat DRN report that most
      serotonin neurons are inhibited by electrical stimulation of the PFC, suggesting
      that this pathway is more likely to synapse onto neighboring gamma-aminobutyric
      acid (GABA) neurons than onto serotonin cells. We tested this hypothesis by
      electron microscopic examination of DRN sections dually labeled for biotin
      dextran amine anterogradely transported from the PFC and immunogold-silver
      labeling for tryptophan hydroxylase (TrH) or for GABA. In the DRN, the majority
      of PFC axons either synapsed onto unlabeled dendrites or failed to form
      detectable synapses in single sections. Other PFC axons synapsed onto either TrH-
      or GABA-immunolabeled processes. Considerably more tissue sampling was necessary
      to detect PFC synapses onto TrH- than onto GABA-labeled dendrites, suggesting
      that the latter connections are more common. In other cases, PFC terminals and
      TrH- or GABA-immunoreactive dendrites either were closely apposed, without
      forming detectable synapses, or were separated by glial processes. These results
      provide potential anatomical substrates whereby the PFC can both directly and
      indirectly regulate the activity of serotonin neurons in the DRN and possibly
      contribute to the pathophysiology of depression.

PMID- 14689485
TI  - Expression of transcripts encoding AMPA receptor subunits and associated
      postsynaptic proteins in the macaque brain.
AB  - Glutamate is the primary excitatory neurotransmitter in the central nervous
      system, regulating numerous cellular signaling pathways and controlling the
      excitability of central synapses both pre- and postsynaptically. Localization,
      cell surface expression, and activity-dependent regulation of glutamate receptors
      in both neurons and glia are performed and maintained by a complex network of
      protein-protein interactions associated with targeting, anchoring, and spatially
      organizing synaptic proteins at the cell membrane. Using in situ hybridization,
      we examined the expression of transcripts encoding the AMPA receptor subunits
      (GluR1-GluR4) and a family of AMPA-related intracellular proteins. We focused on
      PDZ-proteins that are involved in the regulated pool and anchoring AMPA subunits
      to the cell membrane (PICK1, syntenin), and those maintaining the constitutive
      pool of AMPA receptors at the glutamatergic synapse (NSF, stargazin). In
      addition, we studied a fifth protein, KIAA1719, with high homology to the rat PDZ
      protein ABP, associated with the clustering of AMPA receptors at the glutamate
      synapse. The AMPA subunits showed significant differences in regional expression,
      especially in the neocortex, thalamus, striatum, and cerebellum. The expression
      of other proteins, even those related to a specific AMPA subunit (such as ABP and
      PICK1 to GluR2 and GluR3), often had different distributions, whereas others
      (like NSF) are ubiquitously distributed in the brain. These results suggest that
      AMPA subunits and related intracellular proteins are differentially distributed
      in the macaque brain, and in numerous structures there are significant
      mismatches, suggesting additional functional properties of the associated
      intracellular proteins..

PMID- 14689486
TI  - Ventral striatopallidal oxytocin and vasopressin V1a receptors in the monogamous
      prairie vole (Microtus ochrogaster).
AB  - Oxytocin receptors (OTR) and vasopressin V1a receptors (V1aR) in the ventral
      forebrain play critical roles in the formation of pair bonds in the monogamous
      prairie vole. Previous reports have been inconsistent in the identification of
      the specific brain regions in the ventral forebrain that express these receptors.
      To delineate more clearly the neuroanatomical boundaries of the OTR and V1aR
      fields in this species, we compared OTR and V1aR binding in adjacent brain
      sections and also with markers that delineate neuroanatomical boundaries in the
      ventral forebrain. OTR binding displayed an overlapping distribution with
      substance P mRNA and preproenkephalin mRNA, both markers for the shell and core
      of the nucleus accumbens. V1aR binding was nonoverlapping with each of these
      markers but colocalized with iron accumulation as shown by Perls' iron stain as
      well as leucine-enkephalin immunoreactivity, both markers for the ventral
      pallidum. OTR and V1aR mRNA were also restricted within the nucleus accumbens and
      ventral pallidum, respectively. Furthermore, destruction of ventral striatal
      dopaminergic terminals with 6-hydroxydopamine infusions into the nucleus
      accumbens did not alter OTR binding. Immunocytochemical analysis of oxytocin and
      vasopressin in the ventral forebrain demonstrated the presence of oxytocin
      immunoreactive fibers in the nucleus accumbens and vasopressin-immunoreactive
      fibers in the ventral pallidum, with males showing a greater density of
      vasopressin fibers than females, but there was no such sex difference in the
      oxytocin system. Based on these results, we discuss potential neural mechanisms
      by which receptors in these brain regions mediate pair bond formation in this
      monogamous species. J. Comp. Neurol. 468:555-570, 2004.

PMID- 14689487
TI  - Effects of anesthetics on hypoglossal nerve discharge and c-Fos expression in
      brainstem hypoglossal premotor neurons.
AB  - This study examined the effects of anesthesia on the hypoglossal nerve and
      diaphragm activities and on c-Fos expression in brainstem hypoglossal premotor
      neurons (pmXII). Experiments were performed in 71 rats by using halothane
      inhalation, pentobarbital sodium, or mixtures of alpha-chloralose and urethane or
      ketamine and xylazine. First, various cardiorespiratory parameters were measured
      in the rats (n = 31) during both awake and anesthetized conditions. The volatile
      anesthetic halothane, but not the other anesthetics, was always associated with a
      strong phasic inspiratory activity in the hypoglossal nerve. Second, a double
      immunohistochemical study was performed in awake and anesthetized rats (n = 40)
      to gauge the level of activity of pmXII neurons. Brainstem pmXII neurons were
      identified after microiontophoresis of the retrograde tracer Fluoro-Gold in the
      right hypoglossal motor nucleus. Patterns of c-Fos expression at different
      brainstem levels were compared in five groups of rats (i.e., awake or
      anesthetized with halothane, pentobarbital, chloralose-urethane, and ketamine
      xylazine). Sections were processed for double detection of c-Fos protein and
      Fluoro-Gold by using the standard ABC method and a two-color peroxidase
      technique. Anesthesia with halothane induced the strongest c-Fos expression in a
      restricted pool of pmXII located in the pons at the level of the Kolliker-Fuse
      nucleus and the intertrigeminal region. The results demonstrated a major effect
      of halothane in inducing changes in hypoglossal activity and revealed a
      differential expression of c-Fos protein in pmXII neurons among groups of
      anesthetized rats. We suggest that halothane mediates changes in respiratory
      hypoglossal nerve discharge by altering activity of premotor neurons in the
      Kolliker-Fuse and intertrigeminal region.

PMID- 14689488
TI  - Circling behavior in the Ecl mouse is caused by lateral semicircular canal
      defects.
AB  - The epistatic circler mouse (Ecl mouse) is a preexisting mutant, which displays a
      circling phenotype and hyperactivity. It has been shown that the circling
      phenotype in this mutant results from a complex inheritance pattern, but the
      vestibular pathology has not been analyzed. The present study deals with the
      morphological and functional basis responsible for the circling behavior in the
      Ecl mouse. Morphological examination of the inner ears revealed a bilateral
      malformation of the horizontal (lateral) semicircular canal and duct. No cochlear
      abnormalities were detected, and auditory brainstem response (ABR) measurements
      indicated that the auditory system is not affected. Investigation of the
      vestibuloocular reflex (VOR) in Ecl mice showed that their horizontal VOR on
      stimulation is virtually absent, which correlates with the morphological
      findings.

PMID- 14689489
TI  - Morphology and molecular organization of the adult neuromuscular junction of
      Drosophila.
AB  - While the larval neuromuscular junction (NMJ) of Drosophila has emerged as a
      model system to study synaptic function and development, little attention has
      been given to the study of the adult NMJ. Here we report an immunocytochemical
      and morphological characterization of an adult NMJ preparation of the prothorax.
      All muscles examined were innervated by small, uniform type II terminals (0.5-1.5
      microm), a subset of which contained octopamine. Terminals classified as type I
      varied in their morphology across different muscles, ranging from strings or
      clusters of boutons (0.8-5.5 microm) to an elongate terminal (80-100 microm long)
      with few branches and contiguous swellings (3-15 microm) along its length.
      Analysis of the molecular composition of the NMJs during the first 5 days after
      eclosion revealed four major findings: 1) type I boutons increase in size during
      early adulthood; 2) Fasciclin II-immunoreactivity is not detectable at type I
      terminals, while DLG-immunoreactivity is observed at the synapse; 3) a Shaker-GFP
      fusion protein that localizes to all type I boutons in the larva is
      differentially localized at adult prothoracic NMJs; and 4) while all type I
      terminals contain glutamate, the glutamate receptor subunits, DGluRIIA and
      DGluRIIB, are expressed and clustered in only a subset of muscles. These findings
      suggest that maturation of the adult NMJ occurs during early adulthood and that
      muscle-specific properties may play a role in organizing synaptic components in
      the adult. Furthermore, these results demonstrate that there are major
      differences in the molecular organization of the adult and larval NMJs.

PMID- 14689490
TI  - Wear evaluation of cobalt-chromium alloy for use in a metal-on-metal hip
      prosthesis.
AB  - Wear of the polyethylene in total joint prostheses has been a source of morbidity
      and early device failure, which has been extensively reported in the last 20
      years. Although research continues to attempt to reduce the wear of polyethylene
      joint-bearing surfaces by modifications in polymer processing, there is a renewed
      interest in the use of metal-on-metal bearing couples for hip prostheses. Wear
      testing of total hip replacement systems involving the couple of metal or ceramic
      heads on polymeric acetabular components has been performed and reported, but,
      until recently, there has been little data published for pin-on-disk or hip
      simulator wear studies involving the combination of a metallic femoral head
      component with an acetabular cup composed of the same or a dissimilar metal. This
      study investigated the in vitro wear resistance of two cobalt/chromium/molybdenum
      alloys, which differed primarily in the carbon content, as potential alloys for
      use in a metal-on-metal hip-bearing couple. The results of pin-on-disk testing
      showed that the alloy with the higher (0.25%) carbon content was more wear
      resistant, and this alloy was therefore chosen for testing in a hip-simulator
      system, which modeled the loads and motions that might be exerted clinically.
      Comparison of the results of metal-on-polyethylene samples to metal-on-metal
      samples showed that the volumetric wear of the metal-on-polyethylene bearing
      couple after 5,000,000 cycles was 110-180 times that for the metal-bearing
      couple. Polyethylene and metal particles retrieved from either the lubricant for
      pin-on-disk testing or hip simulator testing were characterized and compared with
      particles retrieved from periprosthetic tissues by other researchers, and found
      to be similar. Based upon the results of this study, metal-on-metal hip
      prostheses manufactured from the high carbon cobalt/chromium alloy that was
      investigated hold sufficient promise to justify human clinical trials.

PMID- 14689491
TI  - Tendon surface modification by chemically modified HA coating after flexor
      digitorum profundus tendon repair.
AB  - Carbodiimide derivatized HA (cd-HA) is less soluble in water than normal HA, and
      therefore has an increased tissue residence time. The purpose of this study was
      to study the effect of cd-HA gel on gliding and repair integrity during simulated
      repetitive motion of a repaired tendon in vitro. A total of 36 flexor digitorum
      profundus (FDP) tendons from six adult mongrel dogs were used and divided into
      three groups of control, simple HA, and cd-HA. The gliding resistance between the
      FDP and the proximal pulley, FDS, and bone was measured before laceration and
      after modified Kessler technique repair at 1, 5, 10, 50, 100, 200, 300, 400, and
      500 cycles. After gliding testing, failure load, tendon stiffness, and resistance
      to gap formation were measured. The results showed from the first cycle to the
      10th cycle, there were no significant differences in gliding resistance between
      the three testing groups (p > 0.05). From the 50th cycle onwards, the friction
      was significantly lower in the cd-HA gel group than in the control group (p <
      0.05). Neither breaking strength, nor tendon stiffness, nor resistance to gap
      formation of the repairs were significantly different between the three groups (p
      > 0.05).

PMID- 14689493
TI  - Deproteinizing effects on resin-tooth bond structures.
AB  - This study investigated the effects of NaOCl on resin-tooth bonds to simulate the
      situations of long-term durability and caries invasion. Resin-tooth bonded
      specimens were produced with the use of two resin adhesives (Excite and One
      Bond). Resin-tooth bonded beams (adhesive area; 0.9 mm2) were serially sectioned
      and the specimens were immersed in 10% NaOCl medium for 0 (control), 2, 4, and 6
      h after being stored in water for 24 h. After immersion, microtensile bond tests
      were performed. SEM fractography was conducted to calculate each failure mode by
      image analysis. In addition, the adhesive interface was examined with the use of
      TEM. In the control specimens, enamel bond strengths had no difference between
      Excite (45.6 +/- 15.0) and One-Bond (56.9 +/- 12.9). On the other hand, dentin
      bond strengths had significant difference between Excite (80.6 +/- 21.2) and One
      Bond (50.7 +/- 11.2). The bond strengths decreased with increased storage time
      for both systems with enamel and dentin bonds. The deteriorated mineralized
      dentin of beams resulted in bond-strength reduction for resin-enamel bonds. For
      dentin bonding, the adhesive interface was gradually dissolved from the outer to
      the center portion of the beam. The depletion of collagen fibrils within the
      demineralized dentin or hybrid layer deformation was found under SEM and TEM
      examinations. These morphological changes are responsible for bond strength
      reduction of resin-dentin bonds.

PMID- 14689492
TI  - Does low-intensity pulsed ultrasound stimulate maturation of tissue-engineered
      cartilage?
AB  - Traumatic events are a primary cause of local lesions of articular cartilage.
      Tissue engineered, cartilage-like structures represent an alternative to current
      treatment methods. The time necessary for tissue maturation and the mechanical
      quality of the regenerate at implantation are both critical factors for clinical
      success. Low-intensity pulsed ultrasound has proven to accelerate chondrogenesis
      in vitro. The goal of this study was to evaluate whether low-intensity pulsed
      ultrasound is capable of accelerating the process of cartilage maturation and
      increasing regenerate stability. Hyaline-like cartilage specimens were generated
      in vitro and subcutaneously implanted in the backs of nude mice. Twenty-eight
      animals received 20 min of low-intensity pulsed ultrasound treatment daily, and
      28 animals received a sham treatment. Specimens were explanted after 1, 3, 6, and
      12 weeks, mechanically tested with the use of an indentation test, histologically
      examined, and processed for RT-PCR. The Young's moduli significantly increased
      from 3 to 12 weeks, and at 6 weeks were comparable to those of native articular
      cartilage. In histological examination, specimens showed neocartilage formation.
      There was no significant difference between ultrasound-treated and sham-treated
      groups. The mechanical stability of the neocartilage specimens increased with
      treatment time and reached values of native cartilage after 6 weeks in vivo. Low
      intensity pulsed-ultrasound stimulation showed no stimulatory effect on tissue
      maturation. In contrast, ultrasound-treated specimens showed a reduced Col 2
      expression at 1 week and were significantly less stiff compared to native
      cartilage at 6 and 12 weeks. An acceleration of the maturation of tissue
      engineered neocartilage in a clinical setting by means of low-intensity pulsed
      ultrasound therefore appears rather unrealistic.

PMID- 14689494
TI  - Factors affecting the structure and properties of bioactive foam scaffolds for
      tissue engineering.
AB  - Resorbable 3D macroporous bioactive scaffolds have been produced for tissue
      engineering applications by foaming sol-gel-derived bioactive glasses of the 58S
      (60 mol% SiO2, 36 mol% CaO, 4 mol% P2O5) composition with the aid of a
      surfactant. Bioactive glasses are known to have the ability to regenerate bone,
      and to release ionic biological stimuli that promote bone-cell proliferation by
      gene activation. The foams exhibit a hierarchical structure, with interconnected
      macropores (10-500 microm), which provide the potential for tissue ingrowth and
      mesopores (2-50 nm), which enhance bioactivity and release of ionic products.
      Many factors in the sol-gel and foaming processes can be used to control these
      pore sizes and distributions. This work concentrates on the effect of the
      processing temperature, gelling agent concentration, and the amount of water used
      for the foam generation on the structure, pore morphology, and the properties of
      the foam scaffold. The simplest and most reproducible method for controlling the
      modal pore diameter was by the amount of water added during the foaming process.
      The in vitro dissolution and bioactivity of the bioactive foams were compared to
      that of unfoamed monoliths and powders (< 20 microm in diameter) of the same
      composition.

PMID- 14689495
TI  - The effects of lubricant composition on in vitro wear testing of polymeric
      acetabular components.
AB  - Lubricant composition is known to affect in vitro (simulator) wear of polymeric
      acetabular components. Clinical acetabular components, fabricated from both
      ultrahigh molecular weight polyethylene (UHMWPE) and polytetrafluoroethylene
      (PTFE), were tested against cobalt-chromium 32-mm ball heads, with the use of
      various lubricants, with different compositions and concentrations of bovine and
      calf serum as well as hyaluronic acid, in tests which lasted one million cycles.
      The type of proteins and their relative concentration in the lubricant affected
      the wear rate of both UHMWPE and PTFE. Increasing protein concentration reduced
      the UHMWPE wear rate but increased the PTFE wear rate. For a given total protein
      concentration, increasing the albumin/globulin (A/G) ratio led to a significant
      reduction in the wear rate for PTFE. A similar but smaller effect was found for
      UHMWPE. The relative wear-rate ratio between PTFE and UHMWPE depends on both the
      total protein concentration and the specific protein concentration
      (albumin/globulin ratio). The average clinical wear rates for both PTFE and
      UHMWPE and the average wear-rate ratios between them were reproduced when the
      serum lubricant contained total protein concentration and A/G ratio within
      normally observed physiological ranges. It is recommended that lubricants for
      simulator testing be standardized to control total protein content as well as
      albumin/globulin ratio.

PMID- 14689496
TI  - Platelet adhesion and aggregation on polyethylene: effect of exhaustive exercise.
AB  - The aim of the present study was to evaluate the effect of an exhaustive exercise
      on platelet adhesion and aggregation on polyethylene (PE) in relation to changes
      in plasma cortisol concentration in order to ascertain the effect of physical
      stress response in the blood-contacting properties of polymeric materials. Twelve
      healthy sedentary subjects, six males and six females, were studied. Each subject
      performed an exercise test on a bicycle ergometer at intensity corresponding to
      70% VO2 max until exhaustion. One month after the exercise session, each subject
      participated in a control rest session. In both sessions, blood samples were
      drawn every 5 min for cortisol, lactate, hemoglobin, and hematocrit
      determinations and every 15 min for evaluation of platelet adhesion and
      aggregation. Individual comparisons between the rest and exercise cortisol
      patterns identified three categories of cortisol responders to exercise: positive
      responders (C +, showing higher concentrations during exercise than during rest),
      negative responders (C -, showing lower concentrations during exercise than
      during rest), and nonresponders (NR, showing similar concentrations during
      exercise and rest). The results revealed that C + had lower platelet adhesion and
      aggregation scores during exercise than during rest; moreover C - had higher
      scores than C + and NR during exercise. The results obtained demonstrated no
      effects of sex or exercise on either cortisol plasma levels or platelet adhesion
      and aggregation on PE surface. With regard to cardiovascular risk, the results
      suggest that exercise favorably affects platelet functions when mechanisms of
      metabolic adaptation to prolonged muscular work, expressed by a cortisol
      increase, are activated during exercise.

PMID- 14689497
TI  - Attachment of artificial cartilage to underlying bone.
AB  - The key problem with artificial joint materials is obtaining quick and firm
      attachment onto the underlying bone. In developing artificial articular
      cartilage, composed of polyvinyl alcohol hydrogel (PVA-H), this problem was
      solved by using a composite osteo-chondral device (COD). This enables attachment
      within four weeks post-operation by massive bone ingrowth into the pores. The COD
      consists of PVA-H as an artificial cartilage and titanium fiber mesh (TFM) as
      porous artificial bone. In this study, the strength of the shear resistance force
      at the interface of the PVA-H and the TFM fabricated by injection molding and the
      changes in the mechanical properties of the PVA-H fabricated by high temperature
      during the injection-molding process were examined. The shear resistance force
      was strengthened markedly by using injection molding and no important
      deterioration of the PVA-H was found. Morphological examination of canine spines,
      to which artificial intervertebral discs made of the COD were implanted, showed
      good bonding of the COD with the vertebral bodies for an extended period of 30
      months, and encouraged us to use the COD clinically.

PMID- 14689498
TI  - Chemical, structural properties, and osteoconductive effectiveness of bone block
      derived from porcine cancellous bone.
AB  - The purpose of this study is to determine the efficacy of bioactive calcium
      phosphate obtained from porcine cancellous bone for the treatment of bone defects
      and nonunion. Porcine cancellous bone blocks were heat treated at 1300 degrees C
      for 2 h. The chemical composition, calcium-to-phosphate ratio, and microstructure
      of the porcine bone blocks were examined. For in vivo implantation, bone defects
      were created on the anteromedial aspect of the proximal tibia in seven beagle
      dogs and the xenograft bone blocks were placed into these defects. Plain
      radiographs were taken at 2-week intervals for roentgenographic evaluation. At 12
      weeks, the specimens were stained with hematoxylin and eosin (H&E). The
      composition and morphology of heat-treated porcine cancellous bone were found to
      be similar to heat-treated human cancellous bone. Radiographs showed union
      between the host bone/bone-block interfaces. At 12 weeks, uniform and substantial
      new bone formation was observed. It is concluded that heat-treated porcine
      cancellous bone demonstrated effective osteoconductivity. This high-temperature
      heat-treatment technique has several advantages, including decreased risk of
      disease transmission and immunoreactivity, while also offering excellent
      biocompatibility.

PMID- 14689499
TI  - Comparison of Th1/Th2 cytokine profiles of initial wound healing of rats induced
      by PDCM and e-PTFE.
AB  - Because periodontal regeneration is vital in the modern treatment of periodontal
      defects, artificial membranes have become a key component for predictable
      outcomes. Herein a new ranking system to analyze the expression of different
      cytokines around regenerative membranes is introduced. Porcine dermal collagen
      membranes (PDCMs) and GORE-TEX (e-PTFE) membranes were used for implantation in a
      Sprague Dawley rat model. Tissue samples were harvested at three time intervals
      (7, 10, and 14 days); then an immunohistochemical ranking process was conducted
      to determine the intensity of the selected Th1/Th2 cytokines [Th1: interleukin-2
      (IL-2) and interferone-gamma (IFN-gamma); Th2: IL-4, IL-10, and IL-13]. The
      results show that the intensities of IL-2 cytokine in PDCM groups were slightly
      higher than those of e-PTFE groups but without statistical significance. The
      level of interferon-gamma in PDCM groups was lower than that of e-PTFE groups,
      but also without significant differences. However, expressions of Th2 cytokines
      (IL-4, IL-10, and IL-13) induced by e-PTFE were generally higher than those of
      PDCM and control groups at all times (Mann-Whitney U test, p < 0.05). In a
      comparison of the mean ratio of IL-2/IL-4 with the use of the Mann-Whitney U
      test, data for the PDCM group were generally higher than those of the e-PTFE
      group, with statistical significance at all time intervals (p < 0.05). A
      descending order of the intensity ratio of IL-2/IL-4 was PDCM groups > control
      groups > e-PTFE groups. These findings indicate that the cytokine profiles of
      PDCM, in connection with the GTR technique, demonstrate a higher trend toward Th1
      dominated responses and may protect against periodontal tissue destruction, as
      compared to the Th2-dominated responses of e-PTFE.

PMID- 14689500
TI  - Abrasion resistance of medical glove materials.
AB  - Due to the increasing demand for nonlatex medical gloves in the health-care
      community, there is a need to assess the durability of alternative glove
      materials. This study examines durability characteristics of various glove
      materials by abrasion resistance testing. Natural rubber latex (latex), polyvinyl
      chloride (vinyl), acrylonitrile butadiene (nitrile), polychloroprene (neoprene),
      and a styrene-ethylene/butylene-styrene block copolymer (SEBS) were tested. All
      test specimens, with the exception of the vinyl, were obtained from surgical
      gloves. Unaged out-of-the-box specimens as well as those subjected to various
      degrees of artificial aging were included in the study. After the abrasion
      sequence, the barrier integrity of the material was assessed through the use of a
      static leak test. Other traditional tests performed on these materials were viral
      penetration to validate the abrasion data and tear testing for comparative
      purposes. The results indicate that specific glove-material performance is
      dependent upon the particular test under consideration. Most notably, abrasion,
      even in controlled nonsevere conditions, may compromise to varying degrees the
      barrier integrity of latex, vinyl, SEBS, nitrile, and neoprene glove materials.
      However, as evidenced by the results of testing three brands of neoprene gloves,
      the abrasion resistance of any one glove material may be significantly affected
      by variations in production processes.

PMID- 14689501
TI  - Porous Ti-6Al-4V alloy fabricated by spark plasma sintering for biomimetic
      surface modification.
AB  - Porous compacts with both biological and biomechanical compatibilities and high
      strength were developed. Spherical powders of Ti-6Al-4V alloy, which were either
      as received or surface modified with the use of calcium ions by hydrothermal
      treatment (HTT), were fabricated by a spark plasma sintering process. The porous
      compacts of pure Ti were used as reference materials. Porosity was approximately
      30%, and compressive strengths were 113 and 125 MPa for the as-received Ti alloy
      powders and those modified by the HTT process, respectively. The bending strength
      and elastic modulus of as-received Ti alloy powders were 128-178 MPa and 16-18
      GPa, respectively. Each of the compacts was immersed in simulated body fluid
      (SBF). The amount of adsorption/precipitation of calcium phosphate through the
      compacts was measured by weight change and was observed by SEM. The compacts were
      covered with calcium phosphate after 2 weeks of immersion in SBF. The compacts of
      Ti alloy had plenty of precipitated apatite crystals, and modification by HTT
      accumulated more precipitation. Because calcium phosphate is a mineral component
      of bone, apatite, which is precipitated on the surface of the compacts, could
      adsorb proteins and/or drugs such as antibiotics. It is expected that a large
      amount of proteins and/or drugs could be impregnated when the porous compacts
      developed are used.

PMID- 14689502
TI  - Injectable acrylic bone cements for vertebroplasty with improved properties.
AB  - Currently commercially available acrylic bone cements lack adequate radiopacity
      and viscosity when they are used in percutaneous vertebroplasty (PVP). In this
      work improved formulations of radiopaque and injectable poly(methyl methacrylate)
      bone cements were prepared with different amounts (10-50 wt.%) of BaTiO3 or
      SrTiO3 particles as the radiopaque agent. Two sets of cements were prepared by
      using untreated or silanated radiopaque particles, respectively. The influence of
      the content and nature of the radiopaque agent as well as its silanation with 3
      (trimethoxysilyl) propyl methacrylate (gamma-MPS), on the curing parameters,
      residual monomer content, radiopacity, mechanical properties, and injectability
      of the resulting materials, was examined. Doughing and setting times, maximum
      temperature, and compressive strength of all formulations fulfilled the
      requirements of standard specifications, with values of peak temperature in the
      range 57-72 degrees C and those of compressive strength between 114 and 135 MPa.
      Formulations containing at least 20 wt.% BaTiO3 or SrTiO3 had radiopacities equal
      to or greater than that corresponding to 2 mm of Al as required for surgical
      plastics. Injectability of any of the formulations provided 75-80 wt.% of the
      total mass manually injected through a conventional biopsy needle 4 min after
      mixing. Silanation of the BaTiO3 or SrTiO3 particles led to formulations with
      improved mechanical properties and injectability compared to those obtained with
      the untreated fillers.

PMID- 14689503
TI  - Influence of oscillatory mixing on the injectability of three acrylic and two
      calcium-phosphate bone cements for vertebroplasty.
AB  - Injecting acrylic and, increasingly, calcium-phosphate cements into the porous
      bone structure is an emerging procedure, referred to as vertebroplasty, for the
      augmentation of osteoporotic vertebrae. Despite the benefits of vertebroplasty,
      it has limitations. The limitations of interest in this study are the
      injectability of bone cements and their mixing variability (i.e., low
      reproducibility of resulting viscosity). The objective of this study is to
      investigate the effect of oscillatory versus manual mixing on cement viscosity
      and mixing variability. Five cements are tested: (a) Vertebroplastic, (b) DP
      Pour, (c) Antibiotic Simplex, (d) chronOS Inject, and (e) Biopex. Compared to
      manual mixing, oscillatory mixing significantly decreased the mean viscosity and
      the mixing variability, which was inferred from the coefficient of variation. For
      example, under oscillatory mixing, the viscosity and the variability for
      Vertebroplastic decreased to one-third of the corresponding values for manual
      mixing. Similar results were obtained for the other cements. The decrease in
      viscosity is attributed to the pseudo-plastic behavior of bone cements. The
      decrease in the variability of cement viscosity was attributed to greater
      dispersive mixing of the cement components under oscillatory mixing. The decrease
      in viscosity eases the injection by reducing the pressure required. The decrease
      in the variability of cement viscosity increases reproducibility of the cement
      injection. Oscillatory mixing appears to have the potential to contribute to
      improving vertebroplasty.

PMID- 14689504
TI  - Influence of mixing method on the cement temperature-mixing time history and
      doughing time of three acrylic cements for vertebroplasty.
AB  - Acrylic cements are increasingly being used to augment osteoporotic vertebrae in
      a procedure called vertebroplasty. Two significant factors that may complicate
      the use of acrylic cements are: (a) short handling time, which may result in
      insufficient filling of the vertebra; and (b) exothermic setting (curing)
      behavior, which may result in thermal damage of the surrounding tissue. It has
      been previously reported that mixing the cement components under oscillation, as
      compared to manual mixing, increases the handling time. More specifically, it
      seems that oscillatory mixing slows down the cement polymerization process and,
      consequently, widens the time window during which cement is injectable. However,
      the effect of oscillatory mixing on the exothermic setting behavior of cement
      undergoing polymerization has not been examined. In this study, the exothermic
      setting behavior of three commercially available acrylic cements--Antibiotic
      Simplex, DP-Pour&trade, and Vertebroplastic--were examined for both manual and
      oscillatory mixing methods. For each combination of cement and mixing method, the
      parameters that were measured were the exothermic setting curve (and hence the
      cement setting temperature and setting time) and the cement doughing time. It was
      found that oscillatory mixing had no significant effect on any of these
      parameters. Based on the results of this study, it can be concluded that, for the
      tested cements, the setting process is a reaction-controlled process rather than
      a diffusion-controlled one. Clinically, this implies that oscillatory mixing may
      be used to increase the working period for acrylic cements without increasing the
      risk of thermal damage to surrounding tissue.

PMID- 14689505
TI  - fMRI differences in encoding and retrieval of pictures due to encoding strategy
      in the elderly.
AB  - Functional MRI (fMRI) was used to examine the neural correlates of depth of
      processing during encoding and retrieval of photographs in older normal
      volunteers (n = 12). Separate scans were run during deep (natural vs. man-made
      decision) and shallow (color vs. black-and-white decision) encoding and during
      old/new recognition of pictures initially presented in one of the two encoding
      conditions. A baseline condition consisting of a scrambled, color photograph was
      used as a contrast in each scan. Recognition accuracy was greater for the
      pictures on which semantic decisions were made at encoding, consistent with the
      expected levels of processing effect. A mixed-effects model was used to compare
      fMRI differences between conditions (deep-baseline vs. shallow-baseline) in both
      encoding and retrieval. For encoding, this contrast revealed greater activation
      associated with deep encoding in several areas, including the left
      parahippocampal gyrus (PHG), left middle temporal gyrus, and left anterior
      thalamus. Increased left hippocampal, right dorsolateral, and inferior frontal
      activations were found for recognition of items that had been presented in the
      deep relative to the shallow encoding condition. We speculate that the modulation
      of activity in these regions by the depth of processing manipulation shows that
      these regions support effective encoding and successful retrieval. A direct
      comparison between encoding and retrieval revealed greater activation during
      retrieval in the medial temporal (right hippocampus and bilateral PHG), anterior
      cingulate, and bilateral prefrontal (inferior and dorsolateral). Most notably,
      greater right posterior PHG was found during encoding compared to recognition.
      Focusing on the medial temporal lobe (MTL) region, our results suggest a greater
      involvement of both anterior MTL and prefrontal regions in retrieval compared to
      encoding.

PMID- 14689507
TI  - Feature uncertainty activates anterior cingulate cortex.
AB  - In visual discrimination tasks, the relevant feature to discriminate is defined
      before stimulus presentation. In feature uncertainty tasks, a cue about the
      relevant feature is provided after stimulus offset. We used (15)O-butanol
      positron emission tomography (PET) in order to investigate brain activation
      during a feature uncertainty task. There was greater activity during the feature
      uncertainty task, compared with stimulus detection and discrimination of
      orientation and spatial frequency, in the lateral and medial prefrontal cortex,
      the cuneus, superior temporal and inferior parietal cortex, cortical motor areas,
      and the cerebellum. The most robust and consistent activation was observed in the
      dorsal anterior cingulate cortex (Brodmann area 32; x = 0 y = 16, z = 40). The
      insula, located near the claustrum (x = -38, y = 8, z = 4), was activated during
      the discrimination tasks compared with the feature uncertainty condition. These
      results suggest that the dorsal anterior cingulate cortex is important in feature
      uncertainty conditions, which include divided attention, expectancy under
      uncertainty, and cognitive monitoring.

PMID- 14689506
TI  - Alcohol intoxication effects on visual perception: an fMRI study.
AB  - We examined the effects of two doses of alcohol (EtOH) on functional magnetic
      resonance imaging (fMRI) activation during a visual perception task. The Motor
      Free Visual Perception Test-Revised (MVPT-R) provides measures of overall visual
      perceptual processing ability. It incorporates different cognitive elements
      including visual discrimination, spatial relationships, and mental rotation. We
      used the MVPT-R to study brain activation patterns in healthy controls (1) sober,
      and (2) at two doses of alcohol intoxication with event-related fMRI. The fMRI
      data were analyzed using a general linear model approach based upon a model of
      the time course and a hemodynamic response estimate. Additionally, a correlation
      analysis was performed to examine dose-dependent amplitude changes. With regard
      to alcohol-free task-related brain activation, we replicate our previous finding
      in which SPM group analysis revealed robust activation in visual and visual
      association areas, frontal eye field (FEF)/dorsolateral prefrontal cortex
      (DLPFC), and the supplemental motor area (SMA). Consistent with a previous study
      of EtOH and visual stimulation, EtOH resulted in a dose-dependent decrease in
      activation amplitude over much of the visual perception network and in a decrease
      in the maximum contrast-to-noise ratio (in the lingual gyrus). Despite only
      modest behavior changes (in the expected direction), significant dose-dependent
      activation increases were observed in insula, DLPFC, and precentral regions,
      whereas dose-dependent activation decreases were observed in anterior and
      posterior cingulate, precuneus, and middle frontal areas. Some areas
      (FEF/DLPFC/SMA) became more diffusely activated (i.e., increased in spatial
      extent) at the higher dose. Alcohol, thus, appears to have both global and local
      effects upon the neural correlates of the MVPT-R task, some of which are dose
      dependent.

PMID- 14689508
TI  - Evaluating requirements for spatial resolution of fMRI for neurosurgical
      planning.
AB  - The unambiguous localization of eloquent functional areas is necessary to
      decrease the neurological morbidity of neurosurgical procedures. We explored the
      minimum spatial resolution requirements for functional magnetic resonance imaging
      (fMRI) data acquisition when brain mapping is used in neurosurgical planning and
      navigation. Using a 1.5 Tesla clinical MRI scanner, eight patients with brain
      tumors underwent fMRI scans using spatial resolution of approximately 4 x 4 x 4
      mm(3) to map the eloquent motor and language areas during the performance of
      cognitive/sensorimotor tasks. The fMRI results were then used intra-operatively
      in an open MRI system to delineate eloquent areas. Retrospectively, activation
      patterns were visually inspected by a neurosurgeon to determine qualitatively
      whether ambiguity with respect to the activation boundaries, due to low spatial
      resolution, could be of potential significance for surgical guidance. A
      significant degree of ambiguity in both the extent and shape of activation was
      judged to be present in data from six of the eight patients. Analysis of fMRI
      data at multiple resolutions from a normal volunteer showed that at 3 mm
      isotropic resolution, eloquent areas were better localized within the gray matter
      although there was still some potential for ambiguity caused by activations
      appearing to cross a sulcus. The data acquired with 2-mm isotropic voxels
      significantly enhanced the spatial localization of activation to within the gray
      matter. Thus, isotropic spatial resolution on the order of 2 x 2 x 2 mm(3), which
      is much higher than the resolutions used in typical fMRI examinations, may be
      needed for the unambiguous identification of cortical activation with respect to
      tumors and important anatomical landmarks.

PMID- 14689509
TI  - Left parietal lobe activation to auditory mismatch?
AB  - The original article to which this Commentary refers was published in the
      November, 2002 issue of Human Brain Mapping (Park H-J, Kwon JS, Youn T, Pae JS,
      Kim J-J, Kim M-S, Ha K-S. Statistical Parametric Mapping of LORETA Using High
      Density EEG and Individual MRI: Application to Mismatch Negativities in
      Schizophrenia. Hum Brain Mapp 2002;17:168-178).

PMID- 14689511
TI  - A new protocol for evaluating putative causes for multiple variables in a spatial
      setting, illustrated by its application to European cancer rates.
AB  - We introduce a statistical protocol for analyzing spatially varying data,
      including putative explanatory variables. The procedures comprise preliminary
      spatial autocorrelation analysis (from an earlier study), path analysis,
      clustering of the resulting set of path diagrams, ordination of these diagrams,
      and confirmatory tests against extrinsic information. To illustrate the
      application of these methods, we present incidence and mortality rates of 31
      organ- and sex-specific cancers in Europe; these rates vary markedly with
      geography and type of cancer. Additionally, we investigated three factors
      (ethnohistory, genetics, and geography) putatively affecting these rates. The
      five variables were correlated separately for the 31 cancers over European
      reporting stations. We analyzed the correlations by path analysis, k-means
      clustering, and nonmetric multidimensional scaling; coefficients of the 31 path
      diagrams modeling the correlations vary substantially. To simplify
      interpretation, we grouped the diagrams into five clusters, for which we describe
      the differential effects of the three putative causes on incidence and mortality.
      When scaled, the path coefficients intergrade without marked gaps between
      clusters. Ethnic differences make for differences in cancer rates, even when the
      populations tested are ancient and complex mixtures. Path analysis usefully
      decomposes a structural model involving effects and putative causes, and
      estimates the magnitude of the model's components. Smooth intergradation of the
      path coefficients suggests the putative causes are the results of multiple
      forces. Despite this continuity of the path diagrams of the 31 cancers,
      clustering offers a useful segmentation of the continuum. Etiological and other
      extrinsic information on the cancers map significantly into the five clusters,
      demonstrating their epidemiological relevance.

PMID- 14689512
TI  - Monthly distribution of menarche among schoolgirls from a municipality in
      Southeastern Brazil.
AB  - We studied the monthly distribution of menarche among schoolgirls from Barrinha,
      Brazil, a municipality of rural characteristics in the process of transition to
      urbanization, economically dependent on sugar cane culture and processing. The
      association between season of the year, month of the year, and birth month and
      the occurrence of menarche was evaluated. The schoolgirls who provided the date
      of menarche (month and year) by the recall method and who had menarche up to 36
      months before the interview were selected for analysis (460 girls). The
      correlations between month of occurrence of menarche and month of birth and
      between menarche and seasons of the year were determined by the chi-square test
      and the mean monthly ages at menarche were compared by Student's t-test, with a
      significance level of 0.05. There was a correlation between month of birth and
      month at menarche, with a peak of occurrence of menarche in December not affected
      by the menstruating patterns of maturation, but no correlation between menarche
      and seasons of the year. The difference between mean age at menarche in December
      (spring-summer transition) and in June (autumn-winter transition) was not
      significant. Mean age at menarche during the month following school vacations was
      lower. We conclude that situations of stress-relaxation transition, such as end
      of the school year, beginning of school vacation, and, perhaps most important,
      the socioeconomic factor-the end of the sugar cane harvest, when rural workers
      receive their final payments-favor the occurrence of the peak of menarche in
      December.

PMID- 14689513
TI  - Why are human newborns so fat? Relationship between fatness and brain size at
      birth.
AB  - The plumpness of the human newborn has long been recognized as a trait in need of
      explanation among researchers. Using a linear regression analysis, we find that
      head circumference is significantly and positively associated with BMI at birth,
      after gestational age and birthlength were controlled for, in a sample of 1,069
      healthy liveborn routinely delivered at the University Hospital of Coimbra
      (partial correlation r = 0.409, P < 0.0001). This significant association is
      consistent with the idea that newborn fatness is related to the higher need of
      lipids in newborn humans as an energetic and plastic substrate during its
      accelerated brain growth period. As birthweight and birth head size are
      associated with head size and cognitive abilities in childhood and adult life, it
      could be postulated that these cognitive abilities could have acted as selective
      pressure responsible for the newborn fatness increase in our lineage.

PMID- 14689514
TI  - Month-of-birth effect on height and weight in Polish rural children.
AB  - This study investigated a hypothesis of dependence of child height and weight on
      the month of their birth. The sample comprised 1,241 subjects, 568 boys and 673
      girls, age 6-20 years, from villages in Olsztyn Province, Northeast Poland.
      Individuals' height and weight data were standardized by sex and age to allow
      grouping of individuals born in the same month irrespective of their sex and age
      at examination. Subjects born in October to March proved to be significantly
      taller and heavier than those born in April to September. The magnitude of
      differences between the semiannual groupings equaled 13.1% of a standard
      deviation (SD) in height (P = 0.03) and 14.2% of SD in weight (P = 0.02). The
      month-of-birth effect was much stronger for children characterized by high
      socioeconomic status, where these differences amounted to 39.1% of SD in height
      (P = 0.02) and 49.4% of SD in weight (P = 0.01). There were no regular changes of
      the effect with age and no differences between the sexes were found. Fitted
      cosine functions identified the highest values of examined traits for individuals
      born in December with the lowest values being found in those born in June.
      Possible explanations of the month-of-birth effect are considered in terms of age
      categorizing, seasonal variety of growth rates, as well as birth-related or
      conception-related global, hemispheric, and local factors. This study rejects the
      first two possibilities and suggests this effect requires further research to be
      conducted in various geographical locations, climates, and cultures, on humans as
      well as on other species.

PMID- 14689515
TI  - Contemporary work characteristics, stress, and ill health.
AB  - This study investigates the relationship between work and ill health resulting
      from stressors originating in the work environment. The association between work
      and health has been well-documented. Factors in the work environment leading to
      ill health have included generalized psychological stress and/or specific
      physical environmental characteristics. Data for this study come from a 1998
      telephone survey, the Indiana Survey of Work in a Polarized Economy, under the
      auspices of the Center for Survey Research at Indiana University. The dependent
      variable is an index that measures ill health among workers; control variables
      include sociodemographic and lifestyle characteristics of these workers as well
      as their job characteristics; and the four key independent variables are
      occupational status, organizational disruption, layoff experience, and
      educational discordance of the workers. Multiple regression analysis on the
      entire sample (n = 919) demonstrates that occupational status is negatively
      associated with ill health, while organizational disruption, layoff experience,
      and educational discordance are positively associated with it. Separate analyses
      for male (n = 474) and female (n = 445) respondents find significant sex
      differences in the effects of the key variables: for males, organizational
      disruption is positively related to ill health while for women occupational
      status is negatively related and layoff experience and educational discordance
      are positively related to ill health. The findings from the present research
      provide insight into the interrelationship of occupational environment and health
      within the framework of evolutionary medicine.

PMID- 14689516
TI  - Binary and microsatellite polymorphisms of the Y-chromosome in the Mbenzele
      pygmies from the Central African Republic.
AB  - This study analyzes the variation of six binary polymorphisms and six
      microsatellites in the Mbenzele Pygmies from the Central African Republic. Five
      different haplogroups (B2b, E(xE3a), E3a, P and BR(xB2b,DE,P)) were observed,
      with frequencies ranging from 0.022 (haplogroup P) to 0.609 (haplogroup E3a). A
      comparison of haplogroup frequencies indicates a close genetic affinity between
      the Mbenzele and the Biaka Pygmies, a finding consistent with the common origin
      and the geographical proximity of the two populations. The haplogroups P,
      BR(xB2b,DE,P) and E(xE3a), which are rare in sub-Saharan Africa but common in
      western Eurasia, were observed with frequencies ranging from 0.022 (haplogroup P)
      to 0.087 (haplogroup E(xE3a)). Thirty different microsatellite haplotypes were
      detected, with frequencies ranging from 0.022 to 0.152. The Mbenzele share the
      highest percent of microsatellite haplotypes with the Biaka Pygmies. Five out
      seven haplotypes which are shared by the Mbenzele and Biaka Pygmies belong to
      haplogroup E3a, which suggests that they are of Bantu origin. The plot based on
      F(st) genetic distances calculated using microsatellite data provides a picture
      of population relationships which is in part congruent and in part complementary
      to that obtained using haplogroup frequencies. Finally, the Mbenzele and Biaka
      Pygmies were found to be markedly more genetically similar using Y-chromosomal
      than autosomal microsatellites. We suggest that this could be due to the higher
      phylogenetic stability of Y-chromosome and to the effect of the male-biased gene
      flow during the Bantu expansion.

PMID- 14689517
TI  - Evidence for a major gene underlying bone size variation in the Chinese.
AB  - Osteoporosis is a major public health problem defined as a loss of bone strength,
      of which bone size is an important determinant. In the present study, familial
      correlation and segregation analyses for the spine and hip bone sizes were
      performed for the first time in a Chinese sample composed of 393 nuclear families
      with a total of 1,193 individuals. The results indicate a major gene of
      codominant inheritance for spine bone size; however, there is no evidence of a
      major gene influencing hip bone size. Significant familial residual effects are
      found for both traits, suggesting their polygenic inheritance. Heritability
      estimates (+/-SE) for spine and hip bone size were 0.62 (0.13) and 0.59 (0.12),
      respectively. Sex and age differences in genotype-specific average bone size were
      observed. Compared with our previous study on bone mineral density (BMD) in the
      same population, this study suggests that genetic determination of bone size may
      be different from that of BMD, and thus studying bone size as one surrogate
      phenotype for osteoporotic fractures may be necessary.

PMID- 14689518
TI  - Duffy blood group genotyping in French Basques using polymerase chain reaction
      with allele-specific primers (PCR-ASP).
AB  - Blood group antigens such as Duffy represent interesting models for population
      genetics studies. The distribution of the Duffy blood group was determined using
      PCR in a sample of Basque (n = 126) and non-Basque (n = 110) patients from the
      general hospital of the French Basque Country. The frequency of FY*A allele was
      significantly lower among autochthonous French Basques (P < 0.001). This result,
      obtained for the first time by PCR analysis in this population, was within the
      range of previous historical studies in various Basque subpopulations using
      traditional hemagglutination methods. When compared with European data, our
      Basque sample demonstrated the lowest FY*A/FY*B ratio, this fact confirming
      hemotypology data published before the molecular biology era. Our results with
      FY*X were quite similar to those reported in European populations.

PMID- 14689519
TI  - Prevalence of eight molecular markers associated with thrombotic diseases in six
      Amerindian tribes and two African groups of Costa Rica.
AB  - Individuals belonging to six different Amerindian tribes and two African groups
      of Costa Rica were genotyped for factor V Leiden (FV), factor V haplotype HR2 (FV
      HR2), Factor II 20210G>A (FII), the methylenetetrahydrofolate reductase (MTHFR),
      factor VII polymorphisms (FVII IVS7, FVII R353Q), factor XIII (FXIII V34L), and
      the insertion/deletion (I/D) polymorphism of the gene of angiotensin converting
      enzyme (ACE). Clear differences in the prevalence were found and are first
      reported. The prevalence of some of the established genetic risk factors was low
      in Amerindians of Costa Rica (ACE) or even absent (FVL, FII), and others (MTHFR,
      FVHR2) had an extremely high prevalence. People of African origin carried very
      rare FVL or FII polymorphisms, but the DD genotype of ACE is the highest
      reported. Concerning the protective factors, the QQ genotype of FVII R353Q was
      absent in Amerindians, but the protective 7/7 genotype of FVII IVS7 frequently
      found. Novel alleles of FVII IVS7 (4, 8, and 9 monomers) were found. Intertribal
      heterogeneity was observed that may reflect the evolutionary history of these
      tribal groups and their admixture with other populations.

PMID- 14689523
TI  - Interpregnancy intervals and reproductive success.

PMID- 14689520
TI  - Interpreting skinfold sums. Use of absolute or relative typical error?
AB  - The main aims of this study were to: 1) quantify how divergent the sum of seven
      skinfolds (Sigma7(skinfolds)) of athletes have to be before a general index of
      measurement imprecision (typical error, TE) is no longer appropriate to very lean
      or somewhat overweight athletes, and 2) discuss the application of absolute or
      relative (TE%) typical errors. The Sigma7(skinfolds) was measured in duplicate on
      101 athletes by one level 3 anthropometrist with one calibrated skinfold caliper.
      The TE and TE% for Sigma7(skinfolds) were calculated for all data (TE(ALL),
      TE%(ALL)), as well as for results less than 50 mm (TE(<50), TE%(<50)), inclusive
      of 50-74.9 mm (TE(50-74.9), TE%(50-74.9)), inclusive of 75-99.9 mm (TE(75-99.9),
      TE%(75-99.9)) and 100 mm and greater (TE(>or=100), TE%(>or=100)). At least 20
      samples were taken for each measurement range. Limits of agreement (LoA) at the
      68% and 95% confidence level were also calculated for all data and the four
      skinfold ranges. The TE, TE 68, and 95% LoA increased as a direct function of the
      total Sigma7(skinfolds) and the general TE(ALL) was inappropriate for TE(<50) and
      TE(>or=100). In contrast, the %TE was very similar within each confidence level
      (ranging from 1.6-2.1% and 3.1-4.2% for the 68% and 95% LoA, respectively)
      regardless of the skinfold total. To minimise inaccurate feedback to individuals,
      anthropometrists dealing with skinfolds of elite athletes should establish an
      absolute TE on a homogeneous sample of athletes with a Sigma7(skinfolds) in a
      narrow band, for instance <50 mm. We also urge prudence in interpreting change in
      skinfold totals and suggest that the 95% level of confidence is appropriate in
      most instances.

PMID- 14689521
TI  - D1S80 VNTR locus genotypes in a population of Southeastern Sicily: distribution
      and genetic disequilibrium.
AB  - Locus D1S80 is one of the best-known polymorphic loci, showing a variable number
      of tandem repeats. This article presents the results on D1S80 allele
      distributions in a sample of 324 unrelated Sicilian individuals, collected and
      analyzed in two distinct laboratory centers. Although, as expected, the two most
      frequent alleles were those with 18 and 24 repeat units, the population sample
      from southeastern Sicily showed a relatively low frequency of allele 29 (2.9%)
      and allele 31 (3.4%) and a relatively high frequency of allele 25 (6.0%), allele
      30 (1.9%), and allele 32 (1.5%) in comparison with other populations. Statistical
      analysis performed by the five alleles model provided evidence that the
      population did not follow the Hardy-Weinberg equilibrium expectations (observed
      heterozygosity 70.99% vs. expected heterozygosity 76.31%). The calculated F
      (fixation index), as a measure of heterozygote deficiency or excess, was positive
      for four allele groups and negative for one allele group. This finding was
      consistent with a substantial diversity of human ethnic groups when tested with
      VNTR systems and might represent a genuine inconsistency, not due to a
      methodological bias. This scenario deserves further investigation, i.e., by
      performing a short tandem repeat (STR) units analysis on a greater number of loci
      in the same population sample.

PMID- 14689524
TI  - Mass screening for fetal malformations: the Eurofetus study.

PMID- 14689525
TI  - The role of anal endosonography in obstetrics.

PMID- 14689526
TI  - Relationship between placental blood flow resistance and precordial venous
      Doppler indices.
AB  - OBJECTIVE: To characterize the relationship between placental blood flow
      resistance and precordial venous Doppler indices in normal fetuses. METHODS: This
      was a prospective cross-sectional Doppler study of uncomplicated pregnancies.
      Umbilical artery (UA), inferior vena cava (IVC) and ductus venosus (DV) were
      examined. Multiple indices were calculated for each vein and correlated with the
      UA pulsatility index (PI) and gestational age (GA). In addition, an arteriovenous
      ratio (AV ratio) between the UA PI and multiple venous indices was calculated and
      related to GA. RESULTS: In the 237 patients studied all venous indices showed a
      linear relationship with the UA PI. All venous indices except the IVC preload
      index (PLI) had a significant positive correlation with the UA PI. Seven AV
      ratios were calculated and each had a linear negative relationship with GA. The
      relationship between UA PI and IVC pulsatility index for veins (PIV) and DV PIV
      remained constant throughout gestation. The AV ratio that utilized the IVC PLI
      and DV systolic/a-wave ratio showed a significant decline with GA. CONCLUSION:
      Placental blood flow resistance least influences the IVC PLI while the converse
      is true for the PIV in both veins. A differential effect of placental afterload
      on various venous indices needs to be accounted for in situations of elevated
      placental blood flow resistance. AV Doppler ratios may be useful for this
      purpose.

PMID- 14689527
TI  - Single umbilical artery at 11-14 weeks' gestation: relation to chromosomal
      defects.
AB  - OBJECTIVE: To determine the possible association between single umbilical artery
      (SUA) at 11-14 weeks of gestation and the incidence of chromosomal abnormalities.
      METHODS: Color flow imaging of the fetal pelvis was used to determine the number
      of umbilical arteries in 717 fetuses immediately before chorionic villus sampling
      for karyotyping at 11-14 weeks' gestation. RESULTS: Single umbilical artery (SUA)
      was diagnosed in 21/634 (3.3%) chromosomally normal fetuses, in 5/44 (11.4%) with
      trisomy 21, 14/18 (77.8%) with trisomy 18 and 2/21 (9.5%) with other chromosomal
      defects. In the chromosomally normal group there was no significant difference in
      median fetal crown-rump length or nuchal translucency (NT) between those with a
      single and those with two umbilical arteries. In the 42 fetuses with SUA the
      expected number of cases of trisomy 21, estimated on the basis of maternal age,
      gestational age and fetal NT, was 4.7, which was not significantly different from
      the observed 5. The corresponding numbers for trisomy 18 were 2.0 for expected
      and 14 for observed (Fisher's exact test P = 0.0016). CONCLUSION: A SUA at 11-14
      weeks' gestation has a high association with trisomy 18 and other chromosomal
      defects.

PMID- 14689528
TI  - Ultrasound prediction of risk of spontaneous miscarriage in live embryos from
      assisted conceptions.
AB  - OBJECTIVE: An accurate method to predict subsequent miscarriage in live embryos
      has not yet been established. This pilot study aimed to determine the most
      discriminatory ultrasound-based model for predicting spontaneous miscarriage
      after embryonic life was first detected in assisted conceptions. A method for
      estimating individual risk of miscarriage was developed. METHODS: This was a
      prospective cross-sectional survey of 322 live singleton embryos in women from an
      assisted reproductive technology program. Mean sac diameter (MSD), crown-rump
      length (CRL), embryonic heart rate (EHR), maternal age and gestational age at the
      first transvaginal scan detecting embryonic life (between 42 and 62 days) were
      observed. These variables were included in a multivariate model for predicting
      spontaneous miscarriage occurring prior to 20 weeks. MSD, CRL and MSD minus CRL
      were assessed in univariate logistic regression analyses. The global diagnostic
      accuracy of each model was compared directly using receiver-operating
      characteristics (ROC) curves. RESULTS: The multivariate model demonstrated the
      best ROC curve for predicting miscarriage (ROC area 0.87; 95% CI, 0.80-0.95). The
      separate univariate analyses had less diagnostic accuracy. In particular, MSD -
      CRL had a significantly smaller ROC area (0.65) than did the multivariate model
      (P < 0.01). CONCLUSIONS: The most discriminatory test for predicting spontaneous
      miscarriage in live embryos was a multivariate model, which allows estimation of
      individual risk levels.

PMID- 14689529
TI  - Uterine artery blood flow velocity waveforms during uterine contractions.
AB  - OBJECTIVE: No quantitative or qualitative Doppler velocimetry classification of
      vascular flow resistance covering all stages of forward and reversed flows
      exists. The objective of this study was to characterize uterine artery (UtA) flow
      velocity waveforms (FVWs) obtained during an oxytocin challenge test (OCT) and
      compare them to FVWs in spontaneous normal labor. METHODS: Uterine artery Doppler
      velocimetry was performed during and between uterine contractions in 61 high-risk
      pregnancies subjected to an OCT and in 20 normal pregnancies undergoing
      spontaneous labor. FVWs were classified relative to the presence of
      forward/absent/reversed flow during systole and diastole, and the time-averaged
      flow velocity over the heart cycle. RESULTS: Eleven different FVW classes were
      identified. No relationship between FVWs recorded during uterine inertia and
      contractions was found (P >/= 0.2). In both groups, only forward FVWs were
      recorded between contractions, whereas during contractions flow reversal was more
      common in the OCT group (P </= 0.002). In cases of predominantly reversed flow, a
      reciprocal relationship to FVW classes recorded in the contralateral artery was
      found. CONCLUSIONS: UtA FVW patterns recorded during uterine contractions were
      not predicted by flow patterns recorded during uterine inertia. Reversal of flow
      direction was more common during oxytocin-induced uterine contractions than
      during spontaneous contractions. In cases of predominantly reversed flow, domains
      of the uterus may be supplied by blood from the contralateral UtA. These
      observations give new insights into the circulatory dynamics of the uterus during
      labor, and also point to a possible vasoconstrictory effect in the UtAs of
      oxytocin at high concentrations.

PMID- 14689530
TI  - Evaluation of the measurement of the fetal fat layer, interventricular septum and
      abdominal circumference percentile in the prediction of macrosomia in pregnancies
      affected by gestational diabetes.
AB  - OBJECTIVES: To evaluate the measurement of the fetal abdominal fat layer (FFL),
      cardiac interventricular septum (IVS) and abdominal circumference (AC) percentile
      in the early third trimester as predictors of macrosomia at birth in the fetuses
      of women with gestational diabetes. METHODS: Ninety patients attending the
      hospital's special diabetic clinic were recruited prospectively. FFL and IVS were
      measured in addition to the routine biometry in the early third trimester. AC was
      measured routinely and AC percentile was determined from established antenatal
      charts. These measurements were then assessed as predictors of macrosomia.
      RESULTS: A fetal fat layer of >/=5 mm was the most useful predictor of macrosomia
      at term as assessed using the likelihood ratio. An AC >/=90th percentile,
      however, had a better sensitivity. CONCLUSION: The usefulness of routine FFL
      measurement in the early third trimester in the management of diabetic
      pregnancies is worthy of further evaluation.

PMID- 14689531
TI  - Fetal subcutaneous tissue thickness (SCTT) in healthy and gestational diabetic
      pregnancies.
AB  - OBJECTIVE: To determine reference values of fetal subcutaneous tissue thickness
      (SCTT) throughout gestation in a healthy population and to compare them with
      those from a population of pregnant women with gestational diabetes under
      standard therapy. METHODS: Three hundred and three women recruited from a high
      risk pregnancy clinic were classified as being healthy (n = 218) or as having
      gestational diabetes (n = 85) on the basis of a negative or positive oral glucose
      tolerance test, respectively. They were enrolled into the cross-sectional study
      at 20 weeks' gestation. Ultrasound examinations were performed approximately
      every 3 weeks until delivery at term. The mid-arm fat mass and lean mass (MAFM,
      MALM), the mid-thigh fat mass and lean mass (MTFM, MTLM), the abdominal fat mass
      (AFM) and the subscapular fat mass (SSFM) were evaluated. Time-specific reference
      ranges were constructed from the 218 healthy women and a conventional Student's t
      test was performed to compare SCTT values between the two study groups throughout
      gestation. RESULTS: Normal ranges, including 5th, 50th and 95th centiles of the
      distribution, were generated for each SCTT parameter obtained in each of the two
      groups of women. Significant differences were found between the two study groups
      at 37-40 weeks' gestation for MTFM, at 20-22 and 26-28 weeks for MTLM, at 31-34
      and 35-37 weeks for MAFM, at 26-28 and 38-40 weeks for SSFM, and at 39-40 weeks
      for AFM, the mean residual values always being greater in gestational diabetic
      women than they were in the group of healthy pregnant women. CONCLUSIONS: We
      provide gestational age-specific reference values for fetal SCTT. Fetal fat mass
      values, particularly in late gestation, are greater in women with gestational
      diabetes compared with healthy women. The reference values may have a role in
      assessing the influence of maternal metabolic control on fetal state.

PMID- 14689532
TI  - Ultrasound examination at 37 weeks' gestation in the prediction of pregnancy
      outcome: the value of cervical assessment.
AB  - OBJECTIVE: To examine the potential value of routine measurement of cervical
      length in singleton low-risk pregnancies at 37 weeks of gestation in the
      prediction of onset and outcome of labor. METHODS: Cervical length was measured
      by transvaginal sonography at 37 weeks in 1571 singleton low-risk pregnancies.
      Outcome measures were gestation at spontaneous onset of labor, post-term
      delivery, duration of labor and mode of delivery. RESULTS: The median cervical
      length at 37 weeks was 30 mm and there was a significant association between
      cervical length and gestation at delivery, which increased from a mean of 38
      weeks for cervical length of 10 mm to 41 weeks for cervical length of 35 mm. The
      incidence of delivery after 40 weeks and 10 days was 296 (18.8%) and the
      incidence increased with cervical length at 37 weeks from 0% to 6%, 35% and 68%
      for respective cervical lengths of < 20, 21-30, 31-40 and 41-50 mm. In the
      pregnancies with spontaneous onset of labor the incidence of Cesarean section for
      failure to progress increased from 3.6% to 6.0%, 6.4% and 11.8% for cervical
      lengths of < 20, 21-30, 31-40 and 41-50 mm, respectively. In the pregnancies
      requiring induction for post-term the incidence of Cesarean section for failed
      induction or failure to progress increased from 7.5% to 20.1% to 25.0% for
      cervical lengths of 21-30, 31-40 and 41-50 mm, respectively. CONCLUSION:
      Measurement of cervical length at 37 weeks can define the likelihood of
      spontaneous delivery before 40 weeks and 10 days and the risk of Cesarean section
      in those requiring induction for prolonged pregnancy.

PMID- 14689533
TI  - Sonographic assessment of the cervix before, during and after a uterine
      contraction is effective in predicting the course of labor.
AB  - OBJECTIVE: To investigate whether the degree of change in cervical length during
      a uterine contraction is predictive of subsequent progression of labor. METHODS:
      The subjects were 73 uncomplicated parturient women at term. We observed the
      cervix before, during and after a uterine contraction by transvaginal ultrasound
      in the first stage of labor and determined the degree of cervical shortening
      during the contraction relative to the cervical length before contraction. We
      related the degree of cervical shortening to labor patterns at the time of the
      ultrasound examination, which were retrospectively determined by reviewing the
      partogram. RESULTS: The cervix was shortened in length by about 50% on average
      during a uterine contraction in the normal course of labor. The degree of
      cervical shortening was significantly greater in the normal latent and active
      phases than it was in the prolonged latent phase, protracted active phase and
      false labor, whereas there were no differences between the former two phases nor
      between the latter three phases. Nulliparous and parous women exhibited almost
      the same degree of shortening in the normal latent and active phases.
      CONCLUSIONS: Real-time ultrasound observation of the cervix during uterine
      contraction could help differentiate inefficient uterine contractions from normal
      ones and thus predict the subsequent course of labor.

PMID- 14689534
TI  - Results of endosonographic imaging of the anal sphincter 2-7 days after primary
      repair of third- or fourth-degree obstetric sphincter tears.
AB  - OBJECTIVES: To describe the endosonographic image of the anal sphincter 2-7 days
      after delivery in women who had undergone a primary repair of an obstetric
      sphincter tear. METHODS: Forty-eight women who had suffered a third- or fourth
      degree sphincter tear at delivery and had undergone primary sphincter repair were
      examined with endoanal sonography 2-7 days after delivery. A score from 0 to 16
      was used to describe the extent of the endosonographic defects, a score of 0
      indicating no defect and a score of 16 a defect > 180 degrees involving the whole
      length and depth of the sphincter. Clinical information was retrieved from the
      delivery and operation records after the analysis of the ultrasound images and
      the classification of the sonographic defects had been completed. RESULTS:
      Clinically, 34 (71%) women had a partial third-degree tear, 11 (23%) had a total
      third-degree tear, and three (6%) had a fourth-degree tear. Forty-three (90%; 95%
      CI, 77-97%) women had sonographic defects, all hypoechoic. Twenty-three (54%)
      sonographic defects were confined to the proximal part of the anal canal and
      involved less than half of the length of the anal canal. Thirty (63%) defects
      were confined to the external sphincter. Five of nine women (56%) with an
      endosonographic sphincter defect score >/= 8 had undergone primary sphincter
      repair by a doctor in training vs. 9 of 39 women (23%) with an endosonographic
      sphincter score < 8 (P = 0.05), despite the fact that 86% (12/14) of the tears
      sutured by doctors in training were clinically partial third-degree tears vs. 65%
      (22/34) of those sutured by specialists (P = 0.15). Five (15%) of 34 women with a
      clinical partial third-degree tear had an endosonographic sphincter score >/= 8
      vs. four (29%) of 14 with a clinical total third- or fourth-degree sphincter tear
      (P = 0.26). CONCLUSIONS: Most women (90%) with a clinical third- or fourth-degree
      obstetric sphincter tear have endosonographic sphincter defects if they are
      examined 2-7 days after primary repair. The extent of the endosonographic defects
      seems to be determined mainly by the surgical experience of the doctor performing
      the repair, and not by the clinical degree of the tear.

PMID- 14689535
TI  - Endoanal sonography in assessment of fecal incontinence following obstetric
      trauma.
AB  - OBJECTIVES: Fecal incontinence is a common, incapacitating and largely
      unrecognized medical problem and can be caused by various factors. Obstetric
      trauma is the most common cause of fecal incontinence secondary to trauma. We
      aimed to analyze the role of endoanal ultrasound in assessment of this type of
      fecal incontinence, and report the functional results of surgical treatment.
      METHODS: We reviewed the records of all 22 patients with fecal incontinence
      secondary to obstetric trauma who were evaluated by endoanal ultrasound and
      underwent surgical management in our department from April to 1997 to April 2002.
      Pre- and postoperative evaluation of the degree of incontinence was done using
      the incontinence score of Jorge and Wexner. RESULTS: The patients had a median
      age of 43 (range, 29-68) years. All had vaginal deliveries, five of which (22.7%)
      were instrumental. Most of the patients had total fecal incontinence (solids)
      with preoperative incontinence score values of 15-20 (median, 18). Endoanal
      ultrasound confirmed structural defects in the anterior external anal sphincter
      alone in 16 (72.7%) patients, and both anterior external and internal sphincter
      defects in six (27.3%) patients. A thinned perineal body was present in all
      patients. All patients received surgical treatment with overlapping
      sphincteroplasty and there was improvement of continence in 19 (86.4%) patients
      with postoperative incontinence score values between 4 and 0 (median, 2).
      CONCLUSIONS: Endoanal sonography is an accurate method for assessing sphincter
      anatomy, delineating both internal and external anal sphincters. Surgical
      treatment of sphincter defects is associated with good outcome.

PMID- 14689536
TI  - Assessment of para-aortic lymph nodes by intraoperative sonography in
      gynecological malignancies: a preliminary report.
AB  - OBJECTIVE: To investigate the usefulness of intraoperative sonography for the
      assessment of para-aortic lymph nodes in gynecological malignancies. METHODS: The
      assessment of para-aortic lymph node swelling by computed tomography (CT),
      palpation during surgery and intraoperative sonography was performed in 43 women
      with a gynecological malignancy. The sensitivity, specificity and predictive
      values of each technique for assessment of node metastasis were examined in the
      33 women who underwent para-aortic lymphadenectomy. For each of the three
      assessment techniques, the number of para-aortic lymphadenectomies that would
      have been performed and the number of women who would have had missed metastasis
      were evaluated assuming a para-aortic lymphadenectomy would be performed only
      when swollen nodes were detected. RESULTS: Para-aortic nodes were assessed to be
      swollen by CT, palpation, and intraoperative sonography, respectively, in one,
      six and 10 of 43 women in total, and in one, six and nine of the 33 women who
      underwent para-aortic lymphadenectomy. The sensitivity and negative predictive
      value of intraoperative sonography were 100%, while the specificity and positive
      predictive value of CT were 100%. If para-aortic lymphadenectomy had been
      performed only when swollen nodes were detected by intraoperative sonography, the
      number performed would have decreased from 33 to nine without missing lymph-node
      metastasis. CONCLUSION: Intraoperative sonography has potential for the
      assessment of para-aortic lymph nodes in gynecological malignancies.

PMID- 14689537
TI  - Oscillations of cerebrovascular resistance throughout the menstrual cycle in
      healthy women.
AB  - OBJECTIVES: Increased concentration of endogenous estrogen during a typical
      menstrual cycle has been shown to correlate with augmentation of blood flow
      through the internal carotid arteries (ICAs), which may be related to changes in
      vascular resistance within the brain. In this study we investigated the effects
      of endogenous estrogen and progesterone on cerebrovascular impedance in young
      healthy women. METHODS: The blood flow in the ICA and the common (CCA) and
      external (ECA) carotid arteries was studied with duplex Doppler sonography. The
      resistance index (RI) was determined and correlated with plasma 17beta-estradiol
      concentration in 14 young healthy women throughout their menstrual cycle.
      RESULTS: The concentration of 17beta-estradiol increased in the follicular phase
      of the cycle and reached a peak on day 14, whereas concentration of progesterone
      remained low. Along with an increase in estrogen concentration, the ICA RI had
      decreased from its initial level on average by 9.2% on day 13 and by 6.7% on day
      14 (P < 0.05). In contrast, the trend of the ECA RI was to increase during the
      peak of estrogen concentration. There were no significant changes in the CCA RI
      or in the systolic blood pressure, heart rate, hematocrit and hemoglobin
      concentration through the menstrual cycle. CONCLUSIONS: Estrogen-related
      augmentation of blood flow through the ICA is caused mainly by decreased
      cerebrovascular impedance, as shown by a decrease in the ICA RI. These changes in
      RI suggest that estrogen influences cerebral impedance mainly by altering the
      resistance of cerebral microvasculature.

PMID- 14689538
TI  - The reliability of virtual organ computer-aided analysis (VOCAL) for the
      semiquantification of ovarian, endometrial and subendometrial perfusion.
AB  - OBJECTIVES: Three-dimensional power Doppler angiography (3D-PDA) has been largely
      used for the subjective assessment of vascular patterns but semiquantification of
      the power Doppler signal is now possible. We examined the intraobserver and
      interobserver reliability of the semiquantification of ovarian, endometrial and
      subendometrial blood flow using 3D-PDA, virtual organ computer-aided analysis
      (VOCAL) and shell-imaging. METHODS: 3D-PDA was used to acquire 20 ovarian and 20
      endometrial volumes from 40 different patients at various stages of in vitro
      fertilization treatment. VOCAL was then used to delineate the 3D areas of
      interest and the 'histogram facility' employed to generate three indices of
      vascularity: the vascular index, the flow index and the vascularization flow
      index. Intraobserver and interobserver reliability was assessed by two-way,
      mixed, intraclass correlation coefficients (ICCs) and general linear modeling was
      used to examine for differences in the mean values between each observer.
      RESULTS: The intraobserver reliability for both observers was extremely high and
      there were no differences in reliability between the observers for measurements
      of both volume and vascularity within the ovary or endometrium and its shells.
      With the exception of the outside subendometrial shell volumes, there were no
      significant differences between the two observers in the mean values obtained for
      either endometrial or ovarian volume and vascularity measurements. The
      interobserver reliability of measurements was equally high throughout with all
      measurements obtaining a mean ICC of above 0.985. CONCLUSIONS: 3D-PDA and shell
      imaging offer a reliable, practical and non-invasive method for the assessment of
      ovarian, endometrial and subendometrial blood flow. Future work should
      concentrate upon confirming the reliability of data acquisition and the validity
      of the technique before its predictive value can be truly tested in prospective
      clinical studies.

PMID- 14689539
TI  - Late onset microcephaly: failure of prenatal diagnosis.
AB  - We present a case of recurrent primary developmental microcephaly of late onset,
      the prenatal diagnosis of which could not be achieved despite performing targeted
      serial ultrasound scans that revealed no obvious fetal abnormality. Serial scans
      for head measurements and detailed examination of the brain anatomy by both
      transabdominal and transvaginal sonography including color and power Doppler
      assessment revealed no obvious brain abnormality. Frontal lobe distance and
      thalamic frontal lobe distance at 36 weeks were on the 30th and 50th centiles,
      respectively. Growth velocity remained on the 50th centile up to 36 weeks;
      between 36 and 38 weeks measurements were between the 35th and 40th centiles. The
      infant was delivered by Cesarean section at 38 weeks on parental request. On
      examination after birth the head circumference was on the 9th centile, but the
      facies was that of a microcephalic child with a sloping forehead and
      neurologically he was severely abnormal. The adequacy of the normal reference
      ranges used is reviewed: the use of sex-specific growth charts at 38 weeks would
      have demonstrated the biparietal diameter and the head circumference to be on the
      20th and 15th centiles, respectively, rather than just below the 40th centile.
      However, even sex-specific charts may not allow the recognition of a substantial
      number of affected fetuses.

PMID- 14689540
TI  - Prenatal diagnosis of congenital genu recurvatum following amniocentesis
      complicated by leakage.
AB  - Congenital genu recurvatum (CGR) is an extremely rare condition observed at
      birth. It is associated with, among other malformations, genetic entities such as
      the Larsen syndrome. When CGR is isolated, orthopedic treatment will usually lead
      to a good functional prognosis. We report the first case of isolated CGR
      diagnosed prenatally and suspected to be a consequence of reduced amniotic fluid
      volume due to leakage following amniocentesis. The etiology and management
      options for CGR are briefly discussed.

PMID- 14689541
TI  - Umbilical cord edema associated with patent urachus.
AB  - Umbilical cord anomalies can often be detected prenatally by ultrasound, but a
      definitive prenatal diagnosis is not always possible. We present a case with
      increasing edema of the Wharton's jelly followed by the development of
      pseudocysts in the proximal umbilical cord due to a patent urachus. The first
      abnormal findings were detected by ultrasound in the 14th week of gestation.
      Differential diagnoses and their influence on surveillance and birth management
      are discussed.

PMID- 14689542
TI  - Prenatal diagnosis of a cleidocranial dysplasia-like phenotype associated with a
      de novo balanced t(2q;6q)(q36;q16) translocation.
AB  - Cleidocranial dysplasia (CCD) is a congenital disorder of bone development
      characterized by persistently open or delayed closure of cranial sutures and
      wormian bones, hypoplastic and/or aplastic clavicles, wide pubic symphysis,
      dental anomalies and short stature. The condition is inherited as an autosomal
      dominant trait and the human CBFA1 gene has been identified as the CCD gene. We
      describe a prenatal form of the skeletal disorder that included clavicular
      hypoplasia, absence of ossification of the cranial parietal bones and very poor
      ossification of the frontal and pubic bones. Growth restriction affecting only
      the long bones was also noted. The fetal karyotype revealed an apparently de novo
      balanced t(2q;6q)(q36;q16) translocation. This particular form of skeletal
      disorder associated with the absence of family history and an apparently de novo
      balanced translocation led the parents to opt for termination of the pregnancy.

PMID- 14689543
TI  - First-trimester reversed end-diastolic flow in the umbilical artery is not always
      an ominous sign.
AB  - We report five cases of first-trimester reversed end-diastolic flow in the
      umbilical artery. Diagnoses were performed between 8 and 12 gestational weeks.
      All but one case appeared as a transient early finding. Second-trimester fetal
      demise occurred in two cases. One case delivered at 32 weeks with severe growth
      restriction but recovered well. The other two cases had a good pregnancy outcome.
      Our experience suggests that this early Doppler finding is not always an ominous
      sign.

PMID- 14689544
TI  - Prenatal diagnosis of duodenal atresia with three-dimensional sonography.

PMID- 14689545
TI  - Transvaginal sonographic diagnosis of iniencephaly apertus and craniorachischisis
      at 9 weeks' gestation.

PMID- 14689547
TI  - Choice between using delta-NT or NT MoM.

PMID- 14689548
TI  - Right aortic arch with vascular ring and aberrant left subclavian artery:
      prenatal diagnosis assisted by three-dimensional power Doppler ultrasound.

PMID- 14689549
TI  - John Herbert Beynon.

PMID- 14689550
TI  - John Beynon at Purdue.

PMID- 14689551
TI  - The elusive metastable peak.

PMID- 14689552
TI  - John H. Beynon: the Swansea years 1974-1986.

PMID- 14689556
TI  - J. H. Beynon: list of publications.

PMID- 14689557
TI  - Negative ion electrospray mass spectrometry of aminomethylphosphonic acid and
      glyphosate: elucidation of fragmentation mechanisms by multistage mass
      spectrometry incorporating in-source deuterium labelling.
AB  - Glyphosate and its main metabolite, aminomethylphosphonic acid, introduced by
      direct infusion in (2)H(2)O, appear in negative ion electrospray mass
      spectrometry (ES-MS) as triply deuteriated [M[bond]H](-) ions. Sites of deuterium
      residence and loss were established using the multistage (MS(n)) capabilities of
      an ion trap mass spectrometer to assist in the determination of fragmentation
      mechanisms. The study reveals specific mechanisms, common to each analyte, such
      as those involving a five-membered transition state between the amine and
      phosphonate group, as well as analyte specific transitions.

PMID- 14689558
TI  - Mass spectrometric studies of some novel sulfonamides.
AB  - A recent paper described the overall 5-endo cyclisation of homoallylic
      sulfonamides to give pyrrolidines. This reaction was also used to prepare
      polycyclic systems. Mass spectrometric analysis using classical electron
      ionisation spectra and accurate mass measurement played a vital role in
      confirming the proposed structures for the products. These materials were not
      amenable to newer mass spectrometric methods and this study shows the continuing
      importance of older techniques.

PMID- 14689559
TI  - A study of ion suppression effects in electrospray ionization from mobile phase
      additives and solid-phase extracts.
AB  - Since the wide adoption of liquid chromatography/tandem mass spectrometry
      (LC/MS/MS), the ion suppression/enhancement phenomenon is the latest barrier to
      high-throughput analysis. This consequence of a nonoptimized analytical method
      can lead to adverse effects during quantitation (i.e. poor accuracy and
      precision). Previous papers have reported that ion suppression is a direct result
      of endogenous material present in biological samples. However, in the case of a
      solid-phase liquid chromatography/tandem mass spectrometry (SPE/LC/MS/MS) system,
      the measured result is the combination of several operating conditions and
      parameters. Little has been done to effectively monitor and/or choose optimized
      conditions for the complete sequence of extraction, clean up, separation and
      analysis. This paper describes a simple setup for quantification of ion
      suppression/enhancement. Several mobile phase additives, ion-pairing agents and
      SPE extracts were measured and compared against a standard reference. The results
      demonstrated that a clean up of plasma extracts based on ion exchange leads to
      minimal ion suppression/enhancement for the compounds that were investigated.

PMID- 14689560
TI  - Electron and electrospray ionization mass spectrometry in the characterization of
      some 1-allyl-3-phenylaziridines.
AB  - A series of cis- and trans-isomeric aziridines has been studied under electron
      impact (EI) and electrospray ionization (ESI) conditions. The fragmentation
      patterns of the examined compounds have been elucidated by means of sequential
      product ion fragmentation experiments (MS(n)) performed using an ion trap mass
      spectrometer. Particular attention has been paid to isomer characterization in
      these precursors of azetidinones, that in turn are precursors of new beta-lactam
      antibiotics.

PMID- 14689561
TI  - Study of peptides containing modified lysine residues by tandem mass
      spectrometry: precursor ion scanning of hexanal-modified peptides.
AB  - Upon hexanal-modification in the presence of NaCNBH(3), the oxidized B chain of
      insulin becomes mono- and further dialkylated on both the N-terminal and Lys(29)
      residues. A pseudo-MS(3) study was performed with a triple-quadrupole mass
      spectrometer on the different modified lysine-containing species to gain further
      insights into the characteristic fragmentation pattern. These fragmentations, in
      good agreement with true MS(3) measurements obtained using an ion trap mass
      spectrometer, highlighted characteristic monoalkylated lysine (immonium-NH(3))
      and protonated modified caprolactam ions at m/z 168 and 213, respectively. In
      contrast, no fragment ion derived from a modified lysine residue (immonium or
      caprolactam) was observed when dialkylation occurs on Lys(29). However, a
      fragment ion corresponding to a protonated dihexylamine was observed at m/z 186.
      This loss, characteristic of dialkylated lysine fragmentation, was also observed
      upon dialkylation of N(alpha)-acetyllysine with either hexanal or pentanal. On
      the other hand, acetylation and malondialdehyde-modification of the N(alpha)
      acetyllysine side chain led mainly to the corresponding modified (immonium-NH(3))
      fragment ions at m/z 126 and 138, respectively. Finally, it was demonstrated that
      precursor ion scanning for both m/z 168 and 213 ions led to specific and
      sensitive identification of peptides containing hexanal-modified lysine residues
      within an unfractionated tryptic digest of hexanal-modified apomyoglobin. Thus,
      Lys(42), Lys(45), Lys(62), Lys(63), Lys(77), Lys(87), Lys(96), Lys(98), Lys(145)
      and Lys(147) were found to be modified upon reaction with hexanal.

PMID- 14689562
TI  - Analysis of 21-deoxycortisol, a marker of congenital adrenal hyperplasia, in
      blood by atmospheric pressure chemical ionization and electrospray ionization
      using multiple reaction monitoring.
AB  - Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder mainly
      caused by 21-hydroxylase deficit (21-OHD). Deletions or mutations of the CYP21
      gene induce the impairment of glucocorticoid and mineralcorticoid synthesis. 17
      Hydroxyprogesterone (17-OHP) is the hormonal marker in patients, but not in the
      heterozygous subjects. Excess 17-OHP is hydroxylated into 21-deoxycortisol (21
      DF), and therefore 21-DF can be used as a specific marker for diagnosis of
      heterozygous individuals. We report an analytical method for analysis of 21-DF in
      blood samples using electrospray (ESI) and atmospheric pressure chemical
      ionization (APCI), showing that ESI is very sensitive for the analysis of this
      marker molecule. The multiple reaction monitoring (MRM) approach was used to
      increase the specificity and the sensitivity of the method.

PMID- 14689563
TI  - Sensitive high-performance liquid chromatography/mass spectrometry method for
      determination of steviol in rat plasma.
AB  - The main toxicological concern of stevioside, a highly potent sweetener from S.
      rebaudiana, is its main metabolite, steviol. To determine very low levels of
      steviol in in vivo experiments, a sensitive liquid chromatography/atmospheric
      pressure chemical ionization mass spectrometry (LC/APCI-MS) method was developed
      for quantifying steviol in rat plasma after oral administration of a single dose
      of stevioside (0.5 g/kg). The sample preparation uses liquid-liquid extraction
      with tert-butyl methyl ether in an acidic environment. The retention time of
      steviol was 10.5 min. The assay was linear over the range 2-1000 ng/mL with a
      lower limit of detection of 1 ng/mL. The intra- and inter-day precision were <5
      and <7%, respectively, and the accuracy was in the range 95-108%. The steviol
      concentration profile in rat plasma was determined.

PMID- 14689564
TI  - Regioselective syntheses, structural characterization, and electron ionization
      mass spectrometric behavior of regioisomeric 2,3-disubstituted 2-imino-1,3
      thiazolidin-4-ones.
AB  - The regioselective syntheses of 3-alkyl(aryl)-2-(anthracen-9'-ylimino)-1,3
      thiazolidin-4-ones (2) and 2-alkyl(aryl)imino-3-(anthracen-9'-yl)-1,3-thiazolidin
      4-ones (3) from N-(anthracen-9-yl)-N'-alkyl(aryl)thioureas were accomplished
      effectively using methyl bromoacetate and bromoacetyl bromide, respectively.
      Detailed structural characteristics were confirmed mainly by NMR techniques. The
      mass spectrometric behavior of the resulting sets of compounds of known
      structures was shown to be characteristic for each set. Some interesting
      fragmentation pathways involving the transfer and rearrangements of various
      moieties were also revealed, as well as regioisomerization for particular
      substituent-specific fragmentations.

PMID- 14689565
TI  - Improved procedures for N-terminal sulfonation of peptides for matrix-assisted
      laser desorption/ionization post-source decay peptide sequencing.
AB  - Post source decay (PSD) analysis of precursor ions generated from matrix-assisted
      laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is a
      powerful tool for amino acid sequencing and primary structure analysis of
      proteins. N-Terminal sulfonation has become an effective derivatization strategy
      in facilitating de novo peptide sequencing by the formation of predominate y-type
      ion series in MALDI PSD spectra. Recently, an effective and inexpensive N
      terminal derivatization method has been reported using 4-sulfophenyl
      isothiocyanate (SPITC) as the derivatization reagent (J. Mass. Spectrom. 2003;
      38: 373-377). In this paper, we report an improvement in the derivatization
      procedure with this reagent that involves replacing an organic co-reagent with
      other chemicals and eliminating the use of organic solvent. The method is
      demonstrated on a model peptide and on tryptic digests of two proteins. The
      results indicate that the improved sulfonation reaction can be implemented with
      high efficiency under aqueous conditions and that the sensitivity of mass
      detection can be increased considerably.

PMID- 14689566
TI  - Assignment of quinone derivatives as the main compound class composing
      'interstellar' grains based on both polarity ions detected by the 'Cometary and
      Interstellar Dust Analyser' (CIDA) onboard the spacecraft STARDUST.
AB  - The 'Cometary and Interstellar Dust Analyser' (CIDA) is a particle impact time-of
      flight mass spectrometer onboard the NASA spacecraft STARDUST. A series of
      positive and negative ion mass spectra from the impact of (apparently)
      interstellar dust particles has been collected since 1999. In the meantime
      laboratory work has been performed to better understand the ion formation
      processes of organic grains impacting at those speeds (>15 km/s) and to relate
      them to some other ion formation methods. The key ion types were the negative
      ions, with some additional information from the positive ions. Here, first the
      principal ion formation rules are briefly reviewed. Secondly, the common
      substance class is inferred mainly by the application of exclusion principles,
      and appears to be partly condensed aromatic and quinonoid compounds with high
      oxygen and low nitrogen content. Oxygen appears to be present in quinone-type
      structures with condensed aromatic rings, possibly with furan substructures and
      some hydroxyl moieties. Some nitrogen may be present in pyrrole- or quinoline
      type structures. Considerations of thermodynamics and radiation physics of these
      dust particles within the solar system are consistent with this interpretation.
      Quinoenzyme cofactors such as the known compound pyrroloquinoline-quinone (PQQ)
      and its subconstituents would be expected to yield similar mass spectra.

PMID- 14689567
TI  - Thermodynamic study of some chromium-containing gaseous molecules by high
      temperature mass spectrometry.
AB  - A number of gaseous oxyacid salts have been identified by Knudsen effusion mass
      spectrometry, while vaporizing Cr(2)O(3) and mixtures of Cr(2)O(3)+Nb(2)O(5),
      Cr(2)O(3)+Ta(2)O(5), Cr(2)O(3)+BaO, and Cr(2)O(3)+Mg(2)P(2)O(7) from molybdenum
      and tungsten cells. The stabilities of the gaseous molecules CrMoO(3), CrMoO(4),
      CrMoO(5), CrWO(3), CrWO(4), CrWO(5), CrNbO(3), CrTaO(3), CrPO(2), CrPO(3),
      BaCrO(2) and BaCrO(3) were deduced from the measurements. The thermodynamic
      properties of this gaseous chromium-containing species are summarized. Prediction
      is tentatively made of the stability of as-yet unstudied gaseous molecules.

PMID- 14689568
TI  - N-t-butyliodoacetamide and iodoacetanilide: two new cysteine alkylating reagents
      for relative quantitation of proteins.
AB  - The synthesis and application of two new alkylating reagents, N-tert-butyl-2
      iodoacetamide (N-t-butyliodoacetamide) and 2-iodo-N-phenylacetamide
      (iodoacetanilide), are described. N-t-Butyliodoacetamide and iodoacetanilide were
      synthesised to purity in their d(0)-light and in their respective d(9)- and d(5)
      heavy forms. The newly synthesised reagents are covalently bound to peptides
      containing cysteines via an alkylation reaction. The mass differences of 5 and 9
      Da avoid possible problems of overlapping isotope distribution. For each
      alkylated cysteine a peptide mass increases, respectively, by a multiple of 113
      and 133 Da for the d(0)-light form of N-t-butyliodoacetamide and iodoacetanilide.
      These reagents can therefore replace common alkylating reagents in existing
      proteomics-based applications. Alkylated peptides increase in mass in the same
      mass range as amino acids and remain suitable for tandem mass spectrometry
      (MS/MS) data acquisition and analysis. The compounds are simple to use and
      derivatisation is based on widely applied alkylating procedures. Preliminary
      results show that these reagents can be applied for both protein quantitation and
      identification by peptide mass finger printing and/or MS/MS techniques. Using
      these chemicals and the suggested workflow enables the quantitative analysis of
      the whole protein sample and realises access to peptides that may contain
      potential post-translational modifications. Other approaches that incorporate a
      matrix-assisted laser desorption/ionisation (MALDI) interface prior to MS can
      take advantage of these chemicals, such as the molecular scanner.

PMID- 14689569
TI  - Determination of nabilone in bulk powders and capsules by high-performance liquid
      chromatography/tandem mass spectrometry.

PMID- 14689570
TI  - Flow injection analysis mass spectrometry, a tool to investigate the problems in
      the quantitative analysis of hypericin using reversed-phase high-performance
      liquid chromatography.

PMID- 14689571
TI  - Two additional advantages of proton-transfer ion trap mass spectrometry.

PMID- 14689572
TI  - Hydrophobic component in noncovalent binding of fusion peptides to lipids as
      observed by electrospray mass spectrometry.

PMID- 14689575
TI  - Advances in prostate cancer research.

PMID- 14689576
TI  - Molecular basis for the antiandrogen withdrawal syndrome.
AB  - In patients with prostate cancer who manifest disease progression during combined
      androgen blockade therapy, discontinuation of antiandrogen treatment might result
      in prostate-specific antigen decline, often associated with clinical improvement.
      The response called antiandrogen withdrawal syndrome is thus acknowledged as a
      general phenomenon. However, molecular mechanisms responsible for this syndrome
      are not completely understood. This article outlines the proposed mechanisms,
      including alterations of androgen receptor gene and its coregulatory proteins and
      activation of the signal transduction pathway, and the potential therapeutic
      approaches based on the specific mechanisms.

PMID- 14689577
TI  - Ras signaling in prostate cancer progression.
AB  - When prostate cancer is first detected it generally is dependent on the presence
      of androgens for growth, and responds to androgen ablation therapies. However,
      the disease often recurs in a disseminated and apparently androgen independent
      (AI) form, and in this state is almost invariably fatal. Considerable evidence
      indicates that the Androgen receptor (AR) continues to be required even in
      androgen independent (AI) disease. Thus, a key to understanding hormone
      independent prostate cancer is to determine the mechanism(s) by which the AR can
      function even in the absence of physiologic levels of androgen. In this article,
      we argue that growth factors and receptors that utilize Ras family members drive
      prostate cancer progression to a state of androgen hypersensitivity; and that
      post-translational modifications (e.g., phosphorylations) of transcriptional
      cofactors might be responsible for modulating the function of the AR so that it
      is active even at low concentrations of androgen.

PMID- 14689579
TI  - Role of the extracellular matrix in prostate carcinogenesis.
AB  - This review summarizes the current state of knowledge regarding the proteins
      composing the extracellular matrix in the human prostate. The normal expression
      as well as the changes which occur in PIN and carcinoma are described for the
      lamins, collagens, and glycosaminoglycans.

PMID- 14689580
TI  - Emerging views of integrin signaling: implications for prostate cancer.
AB  - Integrins are heterodimeric transmembrane cellular receptors that link the cell
      to its underlying substratum. Alterations in integrin expression and signaling
      have been implicated in many aspects of tumorigenesis and metastasis including
      cell survival, migration, and invasion. In prostate cancer, the progression from
      normal to metastatic cells is accompanied by changes in the repertoire of
      integrins expressed and up-regulation of key adhesion-dependent signaling
      pathways. Recent work from several laboratories indicates the emergence of new
      mechanisms for the regulation of growth and migratory pathways by integrin
      engagement. These pathways are likely to provide novel sites of therapeutic
      intervention for the treatment of prostate cancer.

PMID- 14689578
TI  - Integrin clipping: a novel adhesion switch?
AB  - During human prostate cancer progression, the majority of normally expressed
      integrins are suppressed with the exception of the alpha6, alpha3, and beta1
      integrins. We have shown that in prostate cancer, the alpha6 integrin is found
      paired with the beta1 integrin and that a novel form of the alpha6 integrin that
      lacks a large portion of the extracellular domain (alpha6p) exists. The
      alpha6pbeta1 integrin is found in human prostate cancer tissue specimens as well
      as tissue culture cell lines and is formed on the cell surface. This review
      discusses the mechanism of alpha6pbeta1 production and the potential functions of
      this integrin variant. Our current working model predicts that the alpha6pbeta1
      integrin maintains the intracellular cytoskeletal connections associated with the
      heterodimer while allowing for an alteration in cell adhesion. The mechanism
      provides a selective advantage for cancer cell metastasis.

PMID- 14689581
TI  - Fatty acid synthase: a metabolic oncogene in prostate cancer?
AB  - In 1920, Warburg suggested that tumors consistently rely on anaerobic pathways to
      convert glucose to ATP even in the presence of abundant oxygen [Warberg, 1956]
      despite the fact that it is less efficient for energy supply than aerobic
      glycolysis. The reasons for this remain obscure to date. More often than not, the
      microenvironment of solid tumors contains regions of poor oxygenation and high
      acidity. In this context hypoxia can act in an epigenetic fashion, inducing
      changes in gene expression and in metabolism for survival. It is reasonable to
      assume that only the tumor cells capable of developing an unusual tolerance to
      limiting oxygen availability and to the acidosis resulting from excessive lactate
      production, can survive. In addition to the striking changes that occur in
      glucose metabolism, studies in human cancer patients suggest that there is often
      also an increase in free fatty acid turnover, oxidation and clearance [Legaspi et
      al., 1987; Hyltander et al., 1991]. For instance, a lipid mobilizing factor
      produced by tumor cells appears to be responsible for the increase in whole body
      fatty acid oxidation [Russell and Tisdale, 2002]. Fatty acids synthesis in tumor
      tissues also occurs at very high rates, as first demonstrated more than half a
      century ago [Medes et al., 1953]. Importantly, (14)C glucose studies have shown
      that in tumor cells almost all fatty acids derive from de novo synthesis despite
      adequate nutritional supply [Sabine and Abraham, 1967; Ookhtens et al., 1984;
      Weiss et al., 1986]. In addition, tumors overexpressing fatty acid synthase
      (FAS), the enzyme responsible for de novo synthesis of fatty acids, display
      aggressive biologic behavior compared to those tumors with normal FAS levels,
      suggesting that FAS overexpression confers a selective growth advantage. Here, we
      will review the roles that FAS plays in important cellular processes such as
      apoptosis and proliferation. In addition, speculations on the putative role of
      FAS in the altered metabolic pathways of prostate cancer cells will be explored.
      Because of the frequent overexpression of this enzyme prostate cancer, FAS
      constitutes a therapeutic target in this disease.

PMID- 14689582
TI  - Cholesterol and prostate cancer.
AB  - Cholesterol is a neutral lipid that accumulates in liquid-ordered, detergent
      resistant membrane domains called lipid rafts. Lipid rafts serve as membrane
      platforms for signal transduction mechanisms that mediate cell growth, survival,
      and a variety of other processes relevant to cancer. A number of studies, going
      back many years, demonstrate that cholesterol accumulates in solid tumors and
      that cholesterol homeostasis breaks down in the prostate with aging and with the
      transition to the malignant state. This review summarizes the established links
      between cholesterol and prostate cancer (PCa), with a focus on how accumulation
      of cholesterol within the lipid raft component of the plasma membrane may
      stimulate signaling pathways that promote progression to hormone refractory
      disease. We propose that increases in cholesterol in prostate tumor cell
      membranes, resulting from increases in circulating levels or from dysregulation
      of endogenous synthesis, results in the coalescence of raft domains. This would
      have the effect of sequestering positive regulators of oncogenic signaling within
      rafts, while maintaining negative regulators in the liquid-disordered membrane
      fraction. This approach toward examining the function of lipid rafts in prostate
      cancer cells may provide insight into the role of circulating cholesterol in
      malignant growth and on the potential relationship between diet and aggressive
      disease. Large-scale characterization of proteins that localize to cholesterol
      rich domains may help unveil signaling networks and pathways that will lead to
      identification of new biomarkers for disease progression and potentially to novel
      targets for therapeutic intervention.

PMID- 14689583
TI  - Death receptor-induced cell death in prostate cancer.
AB  - Prostate cancer mortality results from metastasis and is often coupled with
      progression from androgen-dependent to androgen-independent growth.
      Unfortunately, no effective treatment for metastatic prostate cancer increasing
      patient survival is available. The absence of effective therapies reflects in
      part a lack of knowledge about the molecular mechanisms involved in the
      development and progression of this disease. Apoptosis, or programmed cell death,
      is a cell suicide mechanism that enables multicellular organisms to regulate cell
      number in tissues. Inhibition of apoptosis appears to be a critical
      pathophysiological factor contributing to the development and progression of
      prostate cancer. Understanding the mechanism(s) of apoptosis inhibition may be
      the basis for developing more effective therapeutic approaches. Our understanding
      of apoptosis in prostate cancer is relatively limited when compared to other
      malignancies, in particular, hematopoietic tumors. Thus, a clear need for a
      better understanding of apoptosis in this malignancy remains. In this review we
      have focused on what is known about apoptosis in prostate cancer and, more
      specifically, the receptor/ligand-mediated pathways of apoptosis as potential
      therapeutic targets.

PMID- 14689584
TI  - NF-kappaB activation in human prostate cancer: important mediator or
      epiphenomenon?
AB  - The NF-kappaB family of transcription factors has been shown to be constitutively
      activated in various human malignancies, including leukemias, lymphomas, and a
      number of solid tumors. NF-kappaB is hypothesized to contribute to development
      and/or progression of malignancy by regulating the expression of genes involved
      in cell growth and proliferation, anti-apoptosis, angiogenesis, and metastasis.
      Prostate cancer cells have been reported to have constitutive NF-kappaB activity
      due to increased activity of the IkappaB kinase complex. Furthermore, an inverse
      correlation between androgen receptor (AR) status and NF-kappaB activity was
      observed in prostate cancer cell lines. NF-kappaB may promote cell growth and
      proliferation in prostate cancer cells by regulating expression of genes such as
      c-myc, cyclin D1, and IL-6. NF-kappaB may also inhibit apoptosis in prostate
      cancer cells through activation of expression of anti-apoptotic genes, such as
      Bcl-2, although pro-apoptotic activity of NF-kappaB has also been reported. NF
      kappaB-mediated expression of genes involved in angiogenesis (IL-8, VEGF), and
      invasion and metastasis (MMP9, uPA, uPA receptor) may further contribute to the
      progression of prostate cancer. Constitutive NF-kappaB activity has also been
      demonstrated in primary prostate cancer tissue samples and suggested to have
      prognostic importance for a subset of primary tumors. The limited number of
      samples analyzed in those studies and the relative lack of NF-kappaB target genes
      identified in RNA expression microarray analyses of prostate cancer cells suggest
      that further studies will be required in order to determine if NF-kappaB actually
      plays a role in human prostate cancer development, and/or progression, and to
      characterize its potential as a therapeutic target.

PMID- 14689585
TI  - Galectins and urological cancer.
AB  - Galectins are a family of proteins defined by their affinity for beta-galactoside
      and by their conserved sequence. Each galectins exhibits a specific expression
      pattern in various tissues and their expression is regulated during development.
      Their expression is altered in many types of cancers and non-cancerous disorders.
      They interact with glycoproteins in both extracellular and intracellular milieu
      and regulate various biological phenomenon including cell growth, cell
      differentiation, cell adhesion, and apoptosis. A series of experimental and
      clinical evidences have been reported to support correlation between galectin
      expressions and neoplastic transformation. The recent findings show that
      expressions of galectins are elevated with neoplastic progression in certain
      malignancies, and therefore, galectins are expected to serve as reliable tumor
      markers. In this review, we describe the expression and role of galectins in
      urological cancers and their clinical applications for diagnostic and therapeutic
      use.

PMID- 14689586
TI  - Angiogenesis and prostate cancer tumor growth.
AB  - The initiation of new blood vessels through angiogenesis is critical to tumor
      growth. Tumor cells release soluble angiogenic factors that induce
      neovascularization, without which nutrients and oxygen would not be available to
      allow tumors to grow more than 2-3 mm in diameter. This "angiogenic switch" or
      angiogenic phenotype requires an imbalance between proangiogenic and
      antiangiogenic factors since the formation of new blood vessels is highly
      regulated. This review discusses angiogenesis mediators, and the potential for
      manipulation of angiogenic factors as a practical cancer therapy, particularly in
      prostate cancer.

PMID- 14689587
TI  - Bone morphogenetic protein signaling in prostate cancer cell lines.
AB  - Prostate cancer is the most commonly diagnosed malignancy in men and is often
      associated with bone metastases. Prostate cancer bone lesions can be lytic or
      schlerotic, with the latter predominating. Bone morphogenetic proteins (BMPs) are
      a family of growth factors, which may play a role in the formation of prostate
      cancer osteoblastic bone metastases. This study evaluated the effects of BMPs on
      prostate cancer cell lines. We observed growth inhibitory effects of BMP-2 and -4
      on LNCaP, while PC-3 was unaffected. Flow cytometric analysis determined that
      LNCaP cell growth was arrested in G(1) after bone morphogenetic protein-2
      treatment. Treatment of LNCaP and PC-3 with BMP-2 and -4 activated downstream
      signaling pathways involving SMAD-1, up-regulation of p21(CIP1/WAF1) and changes
      in retinoblastoma (Rb) phosphorylation. Interestingly, bone morphogenetic protein
      2 treatment stimulated a 2.7-fold increase in osteoprotegerin (OPG), a molecule,
      which inhibits osteoclastogenesis, production in PC-3.

PMID- 14689588
TI  - Fingerprinting the diseased prostate: associations between BPH and prostate
      cancer.
AB  - Two of the most common diseases which occur in ageing men relate to their
      prostate. BPH and prostate cancer are prevalent diseases which have an impact on
      most men as they age. The advent of gene expression analysis has provided an
      opportunity to examine these diseases in a novel fashion. These analyses, to
      date, have revealed associations between these two diseases which have not been
      previously identified. These commonalities include global genetic changes which
      occur throughout the prostates in individuals with these diseases. Understanding
      the fingerprints of these diseases is providing novel markers and treatment
      strategies for both BPH and prostate cancer.

PMID- 14689589
TI  - Molecular aspects of diagnostic nucleolar and nuclear envelope changes in
      prostate cancer.
AB  - Prostate cancer is still diagnosed by pathologists based on subjective assessment
      of altered cell and tissue structure. The cellular-level structural changes
      diagnostic of some forms of cancer are known to be induced by cancer genes, but
      the relation between specific cellular-level structural features and cancer genes
      has not been explored in the prostate. Two important cell structural changes in
      prostate cancer-nucleolar enlargement and nuclear envelope (NE) irregularity-are
      discussed from the perspective that they should also relate to the function of
      the genes active in prostate cancer. Enlargement of the nucleolus is the key
      diagnostic feature of high-grade prostatic intraepithelial neoplasia (PIN), an
      early stage that appears to be the precursor to the majority of invasive prostate
      cancers. Nucleolar enlargement classically is associated with increased ribosome
      production, and production of new ribosomes appears essential for cell-cycle
      progression. Several cancer genes implicated in PIN are known (in other cell
      types) to augment ribosome production, including c-Myc, p27, retinoblastoma, p53,
      and growth factors that impact on ERK signaling. However, critical review of the
      available information suggests that increased ribosome production per se may be
      insufficient to explain nucleolar enlargement in PIN, and other newer functions
      of nucleoli may therefore need to be invoked. NE irregularity develops later in
      the clonal evolution of some prostate cancers, and it has adverse prognostic
      significance. Nuclear irregularity has recently been shown to develop dynamically
      during interphase following oncogene expression, without a requirement for post
      mitotic NE reassembly. NE irregularity characteristic of some aggressive prostate
      cancers could reflect cytoskeletal forces exerted on the NE during active cell
      locomotion. NE irregularity could also promote chromosomal instability because it
      leads to chromosomal asymmetry in metaphase. Finally, NE irregularity could
      impact replication competence, transcriptional programming and nuclear pore
      function.

PMID- 14689590
TI  - Are primary cultures realistic models of prostate cancer?
AB  - Primary cultures fill a unique niche among the repertoire of in vitro model
      systems available to investigate the biology of the normal and malignant human
      prostate. This review summarizes some of the properties of primary cultures, with
      special emphasis on two questions: are primary cultures from adenocarcinomas
      really comprised of cancer rather than normal cells, and do primary cultures
      faithfully retain characteristics of cells of origin?

PMID- 14689591
TI  - In vitro culturing and characteristics of transit amplifying epithelial cells
      from human prostate tissue.
AB  - The prostatic epithelium is functionally organized in stem cell units. This unit
      consists of a slow turn over stem cell within the basal epithelial layer which
      can replenish itself and provide progeny which differentiate down either a
      neuroendocrine or exocrine pathway. The maturation along the exocrine pathway
      initially involves transit amplifying cells within the basal layer proliferating
      and subsequently the progeny maturing into intermediate cells. These intermediate
      cells migrate into the luminal layer where they terminally differentiate into non
      proliferative secretory luminal cells which express prostate specific
      differentiation markers, like PSA. A growing body of experimental evidence has
      identified the proliferating transit amplifying/intermediate cells as the cells
      of origin for the common prostatic adenocarcinomas. Using a series of growth
      characteristics, and mRNA and protein markers, we have validated that primary
      cultures can be established in serum free defined media from surgically resected
      human prostates which are composed of essentially pure population of transit
      amplifying cells. At each serial passage, the subsequent cultures undergo
      enhanced maturation into intermediate cells and by the 7-10th passage these cells
      eventually lose their proliferative ability. This study validates that these
      cells are a useful and relevant system for the determination of molecular events
      involved in prostatic carcinogenesis.

PMID- 14689592
TI  - p75 neurotrophin receptor functions as a survival receptor in brain-metastatic
      melanoma cells.
AB  - The p75 neurotrophin receptor (p75(NTR)), a common receptor for members of the
      neurotrophins (NT) family, was previously identified as a molecular determinant
      of brain metastasis. We have also reported that NT treatment of murine and human
      brain-metastatic melanoma cells affects their invasive capacities and increases
      the production of heparanase, an important and unique extracellular matrix (ECM)
      degradative enzyme. Neurotrophism can be a survival-support mechanism for brain
      metastatic cells and a survival assay was devised to mimic the growth limiting
      conditions of rapidly expanding metastatic tumors prior to neoangiogenesis. We
      report that p75(NTR) promoted the survival of brain-metastatic melanoma cells but
      not melanocytes in stress cultures conditions. Secondly, melanoma cells
      fluorescently sorted for high p75(NTR) expression (p75(NTR-H) cells) had an up to
      a 15-fold greater survival than those sorted for low p75(NTR) expression (p75(NTR
      L) cells). Thirdly, cells overexpressing p75(NTR) associated with the growth
      fraction and provided these cells with an inherent growth advantage. Finally, we
      observed an increased survival of sorted p75(NTR-L) cells, dependent upon
      treatment of NT members whose functional receptors are present on these cells.
      Together, these results delineate that p75(NTR)-mediated trophic support
      profoundly affects competitive melanoma-cell survival when the tumor cell
      microenvironment becomes growth limiting.

PMID- 14689593
TI  - Who pays the piper?

PMID- 14689594
TI  - Never say never again.

PMID- 14689595
TI  - One in four.

PMID- 14689596
TI  - Acting out.

PMID- 14689597
TI  - Open doors.

PMID- 14689598
TI  - As well as the problem of stigma, there's the problem of getting better.

PMID- 14689599
TI  - Making us better.

PMID- 14689600
TI  - Double blind random bluff.

PMID- 14689601
TI  - Conspiracy of consensus.

PMID- 14689602
TI  - Substitution for protease inhibitors in HIV therapy.

PMID- 14689603
TI  - Costs of health care administration in the United States and Canada.

PMID- 14689604
TI  - Costs of health care administration in the United States and Canada.

PMID- 14689605
TI  - Costs of health care administration in the United States and Canada.

PMID- 14689606
TI  - Sudden death in young athletes.

PMID- 14689607
TI  - Origin and possible roles of the Sox8 transcription factor gene during sexual
      development.
AB  - Sox8 is a member of the Sox family of developmental transcription factor genes
      and is closely related to Sox9, a critical gene involved in mammalian sex
      determination and differentiation. Both genes encode proteins with the ability to
      bind similar DNA target sequences, and to activate transcription in in vitro
      assays. Expression studies indicate that the two genes have largely overlapping
      patterns of activity during mammalian embryonic development. A knockout of Sox8
      in mice has no obvious developmental phenotype, suggesting that the two genes are
      able to act redundantly in a variety of developmental contexts. In particular,
      both genes are expressed in the developing Sertoli cell lineage of the developing
      testes in mice, and both proteins are able to activate transcription of the gene
      encoding anti-Mullerian hormone (AMH), through synergistic action with
      steroidogenic factor 1 (SF1). We have hypothesized that Sox8 may substitute for
      Sox9 in species where Sox9 is expressed too late to be involved in sex
      determination or regulation of Amh expression. However, our studies involving the
      red-eared slider turtle indicate that Sox8 is expressed at similar levels in
      males and females throughout the sex-determining period, suggesting that Sox8 is
      neither a transcriptional regulator for Amh, nor responsible for sex
      determination or gonad differentiation in that species. Similarly, Sox8 is not
      expressed in a sexually dimorphic pattern during gonadogenesis in the chicken.
      Since a functional role(s) for Sox8 is implied by its conservation during
      evolution, the significance of Sox8 for sexual and other aspects of development
      will need to be uncovered through more directed lines of experimentation.

PMID- 14689608
TI  - Regarding "Cryopreserved saphenous vein allografts in infrainguinal
      revascularization: analysis of 240 grafts".

PMID- 14689609
TI  - Regarding "External iliac artery endofibrosis: a new possible predisposing
      factor".

PMID- 14689610
TI  - Introduction of Prof. Dr. Claus-Frenz Claussen: advances in tinnitology, 1999.

PMID- 14689611
TI  - Between fine arts and science: aspects of the interdisciplinary activities of
      Prof. Dr. Claus-Frenz Claussen. Considerations on the occasion of his sixtieth
      birthday.

PMID- 14689612
TI  - Intratympanic drug therapy with steroids for tinnitus control: a preliminary
      report.
AB  - Intratympanic drug therapy (ITDT) is a surgical technique of instilling
      medication into the middle ear to perfuse the inner ear in treating hearing loss,
      tinnitus, vertigo, and ear blockage, alone or in combination, in patients with a
      predominantly inner-ear site of lesion. This preliminary report of ITDT focuses
      on attempts at tinnitus control (TC). Between November 1997 and February 1999, 10
      patients with severe tinnitus were treated with steroid medication and were last
      seen in February 2000. TC was established in 7 of these 10 patients (70%). The
      clinical diagnosis of a predominantly cochlear-type tinnitus was established in
      each patient by a correlation of the clinical history with a medical-audiological
      tinnitus patient protocol that included cochleovestibular testing. An additional
      single patient with sudden hearing loss experienced no hearing improvement on
      ITDT steroid therapy. Vertigo as an associated complaint was reported by 6 of 10
      patients with subjective idiopathic tinnitus. Significant control of the
      associated vertigo complaint was reported by 5 of 10 patients. Duration of
      tinnitus relief in 7 of 10 patients was hours in 1 of the 7; days in another of
      the 7; and 1 year or more in 5 of the 7. One of the seven patients reported TC 3
      months after the procedure. Complications included tympanic membrane perforation
      that persisted for more than 6 months in two patients and an increase in the
      complaint of ear blockage and tinnitus intensity in one patient. In our
      preliminary study, ITDT with steroid has resulted in both short- and long-term
      tinnitus relief in 7 of 10 patients (70%) identified to have a predominantly
      cochlear-type tinnitus.

PMID- 14689613
TI  - Electroencephalography correlates in tinnitus.
AB  - This study was conducted in an attempt to determine whether the quantitative
      electroencephalograph activity differs between normal control subjects and
      subjects suffering from tinnitus. Results indicated that male tinnitus patients
      as a group had a significantly reduced average total power as compared to control
      subjects. This finding contrasted with female tinnitus patients, who as a group
      had a higher average total power as compared to normal female control subjects.
      Topographical maps (control value-tinnitus value) indicate that with male
      patients, the frontocentral regions of the brain show the greatest difference.
      For the female tinnitus patients, the brain regions most affected are the
      central, parietal, temporal, and occipital regions.

PMID- 14689614
TI  - Cortical evoked response audiometry thresholds and neuroleptic, sedative,
      hypnotic drugs.
AB  - Cortical evoked response audiometry is adequate for approximating hearing
      threshold levels with frequency specificity when the psychoacoustic responses
      lack reliability and reproducibility (compensation claim). It is well-known that
      control of wakefulness is essential for the reliability of slow vertex responses
      (SVR). Therefore, sedative, hypnotic, and neuroleptic drugs are supposed to have
      possible adverse effects on the detection of SVR. In contrast, brainstem evoked
      responses (BER) have proved not to be significantly affected by therapeutic doses
      of these compounds. The purpose of our study was to assess the reliability of SVR
      threshold definition in subjects taking neuroleptic, sedative, and hypnotic
      drugs. Fifteen subjects examined for occupational hearing loss at the Fund for
      Occupational Diseases in Brussels and regularly taking one or several of these
      drugs were compared with 27 comparable controls. In each subject the auditory
      thresholds were defined with both techniques: SVR (1, 2, and 3 kHz) and BER
      (clicks). A highly significant difference is observed between the two groups: In
      the group receiving drugs, the SVR threshold for 3 kHz is 12.1 dB (average)
      higher than the BER threshold, whereas in the group without drugs, the SVR
      threshold for 3 kHz is 7.77 dB (average) lower than the BER threshold. In the
      drug group, large interindividual differences are observed. It may be concluded
      that the use of neuroleptics, sedatives, and hypnotics renders the auditory
      threshold definition with SVR completely unreliable. In using SVR for medicolegal
      threshold definition, controlling the 3-kHz threshold with BER always is
      necessary.

PMID- 14689615
TI  - Competitive-kinesthetic interaction therapy.
AB  - The competitive-kinesthetic interaction therapy is based on several clinical
      observations of patients who are treated with the Brugger therapy in the "Murnau
      approach" and who are suffering from different pain syndromes in their movement
      system. These patients reported definite lessening of their tinnitus, including
      (in some cases) a complete cessation of their subjective ear noise, as a result
      of our therapy on the movement system. Our goal is to modulate and automate the
      civilizatory unforable engraved individual global movement patterns. This
      success, which accompanied the therapeutic removal of movement imbalance and
      related posture and motion disorders, suggests the possibility of influencing the
      balance-surveying organs of the complex equilibrium system, summarizing the
      information from the equilibrium tetrad within a central space-oriented data
      processing system, via the muscles of the entire locomotor system. A very
      important point is that the subjective improvements can be objectified in brain
      electrical activity mapping of vestibular evoked potentials. Two-hundred patients
      were treated with this therapy and were examined between April 1998 and April
      1999.

PMID- 14689616
TI  - Transtympanic pilocarpine in tinnitus.
AB  - In 48 patients who had neurosensory hypoacusia and whose main complaint was
      tinnitus, a 1% pilocarpine solution or a 2% carbachol Isopto solution was placed
      in the tympanic cavity by means of a No. 26 pencil-tipped lumbar puncture needle
      through the front quadrant of the eardrum. Patients were chosen without regard
      for age, gender, or topographical damage of the acoustic pathway. Evaluation of
      the drug's effect was performed audiometrically by masking with the minimum
      intensity of the pure sound or narrow band that most closely resembled the
      patients' own noises. The results of this medical therapy were positive and
      ranged from complete annulment to attenuation of the tinnitus, which was
      confirmed by audiometric masking 30 minutes after the intratympanic injection.
      These positive results reached 50% and would have been higher if the several
      cases submitted by accident insurance companies and cases of presbyacusia were
      discarded. The unsatisfactory element of the study was the short-term effect of
      the therapy, which usually lasted no more than 12-72 hours. Tinnitus reappeared
      in all patients at its original intensity. The best results involved the use of
      carbachol as compared with pilocarpine. The decision to replace pilocarpine with
      carbachol was based on the idea that the inhibitory cholinergic efferent pathways
      are damaged before the afferent pathways. The use of pilocarpine depends on
      efficient cholinergic functioning, as its activity is as an indirect agonist
      (i.e., to annul the cholinesterase enzyme).

PMID- 14689617
TI  - Stress and the onset of sudden hearing loss and tinnitus.
AB  - Forty hospitalized patients with sudden hearing loss and tinnitus were compared
      to a control group (N = 28) of inpatients of an ear-nose-throat ward. They were
      similar in various background variables except for the kind of disorder itself.
      The main objective of our study was to test the hypothesis of stress as a
      predisposing risk factor in the development of sudden hearing loss and tinnitus.
      Thus, differences in life events and daily "hassles" were expected between
      groups, as were differences in coping styles, habitual worrying, and social
      support. The hypothesis of more frequent and more stressful life events and daily
      hassles was supported empirically. The dominant role of daily hassles, especially
      their stressfulness as a risk factor, was shown clearly. Those in the
      experimental group also reported more coping endeavors and more worrying. Social
      support had no discriminating function. The prospective part of the study aimed
      at the prediction of chronicity of sudden hearing loss and tinnitus (3 months
      after onset) by sociodemographic, psychological, and disease-associated
      variables. The strongest predictor of chronicity was the degree of well-being at
      the time of first assessment (soon after disease onset). Coping and a fatalistic
      locus of control also had some predictive power. Methodological limitations of
      the study are discussed.

PMID- 14689618
TI  - Different treatment modalities of tinnitus at the EuromedClinic.
AB  - A retrospective study at the ear, nose, and throat department of the
      EuromedClinic showed considerable improvements immediately after the end of the
      treatments for acute and for chronic tinnitus. Eighty percent of our patients
      suffering from acute tinnitus showed an improvement with intravenous medication
      without hyperbaric oxygen treatment, and 65.7% showed improvement with infusion
      therapy and hyperbaric oxygen. However, at 3 months and then later (long-term
      results), the figures decreased to 67% and 46%, respectively. In the chronic
      tinnitus group, the therapeutic effect dropped from 66.7% to 34% (with only
      intravenous medication) and from 60% to 28% (with combined therapy). These facts
      can explain the importance of beginning the treatment of patients suffering from
      tinnitus as early as possible (i.e., acute stage).

PMID- 14689619
TI  - Ginkgo biloba: local experiences.
AB  - Ginkgo biloba (EGb 761) as a phytotherapeutic agent used in otoneurology,
      psychiatry, and ophthalmology. We studied the efficacy of therapy with EGb 761 in
      72 patients (44 male and 28 female) with chronic cochleovestibular disorders. We
      used pure-tone audiology, measuring pure-tone average, speech reception
      threshold, and speech discrimination score. Then we used craniocorpography to
      measure lateral body sway and angular deviation. Finally, we used nystagmography
      (central nystagmic frequency). Also, we assessed subjectively the variation in
      patients' comfort. We concluded that EGb 761 has a very good effect on both
      postural and oculovestibular reflexes. Also, hearing was improved, and patients'
      comfort was considered to be heightened by the therapy.

PMID- 14689620
TI  - Gingko biloba (Rokan) therapy in tinnitus patients and measurable interactions
      between tinnitus and vestibular disturbances.
AB  - Tinnitus is one of the most important symptoms in neurootology after vertigo,
      nausea, and hearing loss. In most cases, the origin of the tinnitus remains
      inexplicable. Well-known, however, is that tinnitus may arise in any part of the
      hearing pathway (i.e., both within the cochlea receptor and in the temporal lobe
      and projections). Tinnitus also is associated frequently with vertigo, nausea and
      hearing loss. An age predominance exists, with tinnitus more common among those
      older than 40 years. From this starting point, a great demand exists today for
      new ideas and developments in the diagnosis and treatment of tinnitus.

PMID- 14689621
TI  - Drug treatments for tinnitus: the Tulane experience.
AB  - It has recently been estimated that 12 million Americans have a severe form of
      tinnitus and that nearly 40 million Americans suffer from some form of tinnitus
      related complaints [1]. The nature of patients' concerns at the time of the
      initial evaluation is very important in our overall patient management. Specific
      issues that we address in our practice include the following: (1) Why are
      patients here? (2) What do patients want and what do they expect of me? (3) Whom
      have they seen before and what if anything has been tried and proved ineffective
      in treating their condition? Each of these basic questions must be answered to
      ensure that we are addressing affected patients' concerns and are targeting our
      efforts according to individual patients' needs.

PMID- 14689622
TI  - Audiovestibular findings prior to and after acoustic neuroma surgery.
AB  - We performed a retrospective study of 131 patients who underwent microsurgical
      removal of statoacoustic neuroma at the University of Wuerzburg. Our goal was to
      evaluate objective audiovestibular findings prior to and after surgery. Our
      analysis focused on the evaluation of quantitative parameters in speech and pure
      tone audiometry and on the reactivity of the vestibular system.

PMID- 14689624
TI  - Development of clinical neurootological network diagnostics during the last three
      decades.

PMID- 14689625
TI  - Computer applications in neurootology.

PMID- 14689627
TI  - Degeneration of the hearing nerve and its detection by distorted-speech testing.
AB  - A detailed description of the physiology of the auditory system (including new
      essential knowledge) is provided, followed by the description of five
      morphological levels of acoustic signal analysis, of which four play a
      significant part in establishing the selection capacity of human hearing. As an
      essential phenomenon connected with loss of the analyzing capacity of the ear,
      ascending degeneration of the afferent nerve fibers of the inner hair cells and
      of the hearing nerve (after destruction of the inner hair cells) develops. A
      distorted-speech test is submitted that offers a simple and easily performed
      calculation of a ratio, which value renders a reliable estimation of the
      pathological analyzing capacity of the ear caused by ascending degeneration. The
      test is recommended as a reliable basic component of an audiometric battery of
      tests.

PMID- 14689626
TI  - Benzodiazepine receptor deficiency and tinnitus.
AB  - As regards the symptom of a predominantly central tinnitus of the severe,
      disabling type, it has been hypothesized that a deficiency in the benzodiazepine
      receptor exists in the medial temporal lobe system of brain and is directly
      related to affect impairments including anxiety, stress, depression, and fear.
      This hypothesis has been investigated with single-photon emission computed
      tomography using the benzodiazepine radioligand 123I Iomazenil. Visual analysis
      revealed preliminary results of diminished benzodiazepine-binding sites in the
      medial temporal cortex of all patients with severe tinnitus (N = 6), a finding
      that is consistent with the hypothesis implicating GABAergic mechanisms in the
      pathophysiology of the disorder. An abnormal gamma-aminobutyric acid--A
      benzodiazepine receptor density may be an objective neurochemical measure of the
      severity of a central-type tinnitus and a rationale for treatment. Clinical
      correlation with the history, clinical course of the patient, and stress
      questionnaire are presented.

PMID- 14689628
TI  - Effect of microgravitation on the human equilibrium.
AB  - The 38-year period of human space exploration has gained for us a lot of
      experience in the problem of space motion sickness. The authors collected some
      causes of space sickness from the literature and from their research results. We
      collaborated with the Soviet-Russian space researchers and elaborated those
      vestibular research methods that were carried out by human space missions in the
      Soviet-Russian space station, on Earth, and after flight: spontaneous eye
      movement, foveal and peripheral optokinetic nystagmus, and vestibular
      stimulation. Using an earthly model of the effect of microgravitation on the
      human body, we tried to provide explanations of the origin of space motion
      sickness.

PMID- 14689629
TI  - Quantitative electroencephalography and tinnitus: a case study.
AB  - We report changes in quantitative electroencephalography activity in a male
      tinnitus patient when his tinnitus suddenly disappeared. Topographical
      illustration of the quantitative electroencephalography data showed beta foci in
      T3 and C4 with tinnitus, which resolved on spontaneous remission of the tinnitus.
      Comparison of the power spectra in the presence and absence of tinnitus revealed
      significant changes of a 16-Hz band. Also, a significant increase in alpha power
      was observed after remission of the tinnitus.

PMID- 14689630
TI  - Longitudinal follow-up of occupational status in tinnitus patients.
AB  - In this study, the long-term outcome of tinnitus patients was studied in terms of
      changes in occupational status from admission to follow-up for an average
      duration of 5 years. A consecutive series of 189 tinnitus patients seen between
      the years 1988 and 1995 were sent a postal questionnaire booklet; 146 provided
      usable responses (a 77% response rate). Results showed a significant change in
      occupational status, which was explained partly by retirement because of old age.
      Few were unemployed at follow-up, and relatively few were on sick leave. These
      data suggest that tinnitus patients may be less of a demand for the sickness
      benefit system in Sweden, but it may reflect also that tinnitus is not accepted
      as a cause for sick absenteeism.

PMID- 14689631
TI  - Secondary tinnitus as a symptom of instability of the upper cervical spine:
      operative management.
AB  - Tinnitus very often is caused by instability of the craniocervical junction. It
      very frequently manifests as a high-pitched whistle that disappears after
      operative correction and stabilization of the articular geometry. Prolapsed
      intervertebral disks, discoligamentous injury, and even metastases as low as
      level C3 can cause tinnitus, which also usually disappears after surgery.

PMID- 14689632
TI  - Functional magnetic resonance imaging--video diagnosis of soft-tissue trauma to
      the craniocervical joints and ligaments.
AB  - Patients suffering from distortion of the cervical spine after an acceleration
      trauma present problems with respect to the correct diagnostic recognition of the
      existing injuries. To define instability of the craniocervical junction,
      attention should be given to the position of the dens and the dimension of its
      subarachnoid space during the entire rotational maneuver. Our diagnosis via
      functional magnetic resonance imaging (fMRI) with video did not focus on injuries
      to the ligamentous microstructure as visualized with high-resolution MRI. Our
      purpose was to demonstrate the cause of instability of the craniocervical
      junction by direct visualization during fMRI-video technique. Between December
      1997 and March 1999, 200 patients were studied using fMRI on a 0.2-Tesla Magnetom
      Open. Routine evaluation of the extracranial vertebral circulation by MRI
      angiography as an additional preinvestigative requirement is recommended. The
      earliest examination time from injury to MRI evaluation was 3 months and the
      maximum, 5 years (average, 2.6 years). Among the 200 patients investigated, 30
      showed instability of the ligamentous dens complex. Of the same 200, 8 (4%) had a
      complete rupture and 22 (11%) an incomplete rupture of the alar ligament, with
      instability signs. In another 45 patients (22.5%), fMRI-video showed evidence of
      instability, and all these patients had coexisting intraligamentous signal
      pattern variation, probably due to granulation tissue. Eighty patients of the 200
      (40%) had signal indifference without demonstrable video instability signs, and
      43 patients (21.5%) showed no evidence of instability and no signal variation in
      the alar ligaments. On the basis of recognition of instability and the
      malfunction of the ligaments, the fibrous capsula, and the tiny dens capsula, we
      now can distinguish between lesions caused by rotatory trauma to the
      craniocervical junction and those from classic whiplash injury.

PMID- 14689633
TI  - Sonovestibular symptoms evaluated by computed dynamic posturography.
AB  - The investigation of stability under bilateral acoustic stimulation was
      undertaken in an attempt to mimic the real-life conditions of noisy environment
      (e.g., industry, aviation). The Tullio phenomenon evaluated by computed dynamic
      posturography (CDP) under acoustic stimulation is reflected in postural
      unsteadiness, rather than in the classic nystagmus. With such a method, the
      dangerous effects of noise-induced instability can be assessed and prevented.
      Three groups of subjects were submitted. The first (group A) included 20 patients
      who complained of sonovestibular symptoms (i.e., Tullio phenomenon) on the
      background of an inner-ear disease. The second group (B) included 20
      neurootological patients without a history of Tullio phenomenon. Group C
      consisted of 20 patients with normal hearing, as controls. A pure-tone stimulus
      of 1,000 Hz at 110 dB was delivered binaurally for 20 seconds during condition 5
      and condition 6 of the CDP sensory organization test. The sequence of six sensory
      organization conditions was performed three times with two intermissions of 15-20
      minutes between the trials. The first was performed in the regular mode (quiet
      stance). This was followed 20 minutes by a trial carried out in quiet stance in
      sensory organizations tests (SOTs) 1 through 4, and with acoustic stimulation in
      SOT 5 and SOT 6. The last test was performed in quiet stance throughout
      (identical to the first trial). A significant drop in the composite equilibrium
      score was witnessed in group A patients upon acoustic stimulation (p < .0001).
      This imbalance did not disappear completely until 20 minutes later when the third
      sensory organization trial was performed. In fact, the composite score obtained
      on the last SOT was still significantly worse than the baseline. Group B and the
      normal subjects (group C) showed no significant change in composite score. As
      regards the vestibular ratio score, again, group A marked a drop on stimulation
      with sound (p < .004). This decrease contrasted once more with the other two
      groups. The leading sensory organization pattern was vestibular dysfunction
      (i.e., 40%, 10%, and 0% before acoustic stimulation in groups A, B, and C,
      respectively). The initial proportion of vestibular dysfunction increased on
      acoustic stimulation to 55% in group A, but this subsequently decreased in the
      third trial. The percentages of vestibular dysfunction remained constant during
      repeated trials in the other two groups. The positive medical history of
      sonovestibular symptoms was confirmed objectively by CDP with sound stimulation
      with a high statistical significance. This establishes the described method as a
      sensitive testing technique for validating the existence of the Tullio phenomenon
      in patients with a variety of disorders of the inner ear, especially chronic
      noise-induced hearing loss and acute acoustic trauma. All patients who suffered
      phonic trauma, chronic exposure to noise (e.g., aviation employees, industry and
      army personnel), or other neurootological disorders and who complain of
      sonovestibular symptoms should be tested for the presence of the Tullio
      phenomenon. This should be carried out preferably by means of CDP with acoustic
      stimulation for an objective corroboration of their complaint before continuing
      activity in a noisy environment, thus preventing dangerous loss of balance when
      exposed to noise.

PMID- 14689634
TI  - Effect of aging on saccadic eye movements to visual and auditory targets.
AB  - Elderly patients with diseases of the central nervous system often show saccadic
      disorders. Before these disorders can be called pathological, they must be
      distinguished from the physiological effects of aging. The purpose of this study
      was to determine the effect of aging on visual and auditory saccadic eye
      movements. Ninety healthy volunteers were divided into three groups (younger than
      30 years; 30-50 years; older than 50 years), with 30 volunteers in each group.
      Visual and auditory predictive 15-degree saccades were evoked and recorded with
      electrooculography. Recorded parameters were peak velocity, duration, and
      latency. Both stimuli showed increasing latencies with increasing age and a
      higher peak velocity in the middle group as compared to the oldest group. The
      latter result was significant only for saccades to visual targets. Duration was
      almost identical for both patterns and all age groups. Between the age groups,
      latencies were significantly shorter for the saccades to auditory targets, and no
      differences in peak velocity occurred. The results stress the importance of an
      age-related assessment for saccadic parameters. The increasing latency and
      decreasing peak velocity in elderly people probably result from age-related
      degenerative changes in central nervous system parts that are involved in the
      generation of saccadic eye movements. We found no indications of a different
      effect of aging through either the visual or the auditory pathway for saccadic
      parameters.

PMID- 14689635
TI  - Olfactory evoked responses in Alzheimer's disease.
AB  - In Alzheimer's disease, a rapid adaptation was recognized by suprathreshold
      odorant stimulation. This adaptation in Alzheimer's disease may be caused by
      dysfunction of the mechanism in adaptation of a quickly recovering central
      process.

PMID- 14689636
TI  - Caloric eye-tracking pattern test: visual suppression and the possibility of
      simplified differential diagnosis between peripheral and central vertigo.
AB  - During the examination of patients who complain of vertigo or who have
      equilibrium disorders, often identifying the etiology of the disorders is
      difficult (i.e., determining whether it is dependent on a peripheral or a central
      vestibular disorder). To attempt to determine the etiology in these cases, we
      devised a new method: the caloric eye-tracking pattern test. In normal subjects
      and in patients with peripheral disorders, as is well-known, caloric nystagmus
      has little influence on the eye-tracking pattern. In contrast, in patients with
      central vestibular disorders, caloric nystagmus evoked abnormalities in the eye
      tracking pattern, either superimposed or as saccades, despite the fact that the
      eye-tracking pattern before caloric stimulation was normal. These findings result
      from the visual suppression mechanism to vestibular nystagmus. We can conclude
      that the visual suppression to vestibular nystagmus is evoked more strongly by
      pursuing a moving visual stimulus than by gazing at a stationary target. These
      results are interesting, not only from the physiological viewpoint but from the
      clinical viewpoint. The differential diagnosis should include both peripheral and
      central vertigo.

PMID- 14689637
TI  - Spontaneous otoacoustic emissions in neonates and effect of contralateral white
      noise stimulation.
AB  - Neonates younger than the age of 12 weeks (10 full-term, 20 preterm) had an
      audiological assessment consisting of brainstem audiometry, tympanometry,
      transiently evoked otoacoustic emissions, and spontaneous otoacoustic emissions
      with contralateral white noise stimulation. Results from brainstem audiometry,
      tympanometry, and transiently evoked otoacoustic emissions suggested normal
      middle ear function and normal cochlear function. All full-term neonates had
      multiple spontaneous otoacoustic emissions, and contralateral white noise
      stimulation resulted in enhancement of emissions in 80%, whereas in 20% the
      emissions were suppressed. In preterm neonates, spontaneous otoacoustic emissions
      were present in 55%. These emissions were mostly solitary and, in 64%, showed
      suppression with contralateral white noise stimulation. Embryological data taken
      into consideration suggest that the pattern of spontaneous otoacoustic emissions
      in preterm neonates is more likely related to immaturity of the central auditory
      pathway rather than the cochlea.

PMID- 14689638
TI  - Electronystagmographic study in chronic schizophrenia.
AB  - The authors reached the neurological and psychiatric diagnosis of chronic
      schizophrenia in 20 patients after examination of both vestibulooculomotor and
      visuooculomotor reflexes on electronystagmography. The type and intensity of the
      disease were established on adequate scales, and the entire group was tested in
      the remission stage, during the absence of psychotic signs.
      Electronystagmographic study, particularly the eye-tracking test with caloric
      modification, revealed the significant pathology of optokinetic nystagmus. The
      disturbances of the suppression effect of fixation on caloric nystagmus were
      observed in one-half the cases. Caloric stimulation demonstrated no case of canal
      paresis and a very small amount of directional preponderance.

PMID- 14689639
TI  - A comparison between middle latency responses and late auditory evoked potentials
      for approximating frequency-specific hearing levels in medicolegal patients with
      occupational hearing loss.
AB  - To evaluate the medicolegal relevance of middle latency responses for objectively
      approximating frequency-specific hearing levels in subjects with occupational
      hearing loss, we compared the middle latency response with the cortical response
      in 22 reliable subjects who had noise-induced hearing loss and were submitting
      claims for compensation and 21 subjects who had noise-induced hearing loss but
      were exaggerating the level of this loss and also were submitting claims for
      compensation. Middle latency components of auditory evoked potentials, especially
      the time-saving 40-Hz response, seem efficient and reliable for evaluating the
      true pure-tone thresholds (1, 2, and 3 kHz). A good correlation exists between
      the 40-Hz response threshold and the slow vertex response (SVR) threshold (long
      latency). Both also show a fairly close correlation with behavioral thresholds in
      cooperating subjects. However, in most cases, the 40-Hz response is less
      sensitive (mode of difference, 10 dB) than is the SVR. As middle latency response
      audiometry is not actually a time-saving procedure in comparison with cortical
      evoked response audiometry and as it seems less sensitive than the SVR for
      approximating the true threshold, the use of middle latency response audiometry
      seems best limited to situations in which a control or a confirmation of the SVR
      is wanted. Further information about the sensitivity of middle latency response
      to drug effects and to subject wakefulness (specifically, whether the patient is
      more or less sleepy) is expected.

PMID- 14689640
TI  - Neurootological aspects of medical expertise in whiplash-associated disorders.
AB  - After summarizing the neurophysiological aspects of whiplash injury, the author
      proposes a guide for neurootological evaluation in relation to the
      pathophysiology of the injury.

PMID- 14689642
TI  - Blood-labyrinth barrier and fluid dynamics of the inner ear.
AB  - Under normal conditions, the inner ear possesses remarkably stable homeostatic
      mechanisms for the maintenance of functional integrity of the inner ear fluid.
      The inner ear fluid maintains its homeostasis by a variety of regulatory
      mechanisms such as an ion transport system, a blood-labyrinth barrier, and a
      constant blood supply. Highly regulated transport of ions into and out of the
      inner ear provides for the maintenance of inner ear fluid composition necessary
      for auditory transduction. Any disturbance in one of these mechanisms can disrupt
      homeostasis expressed by ionic, osmotic, or metabolic imbalance between the
      compartments. Free radicals, stress hormones, noise exposure, and aminoglycoside
      antibiotics may induce short- and long-term effects on cellular function of the
      auditory or vestibular system (or both) and serve as a triggering mechanism for
      abrupt functional disturbances of inner ear fluid ion homeostasis. In this
      article, we present a comprehensive review of the mechanisms underlying inner ear
      fluid homeostasis necessary for normal auditory function and factors that can
      disrupt homeostasis and lead to functional disturbances, namely sensorineural
      hearing loss, tinnitus, and vertigo.

PMID- 14689643
TI  - Neck flexion, extension, and rotation test.

PMID- 14689644
TI  - Noise exposure and its effect on the labyrinth, Part I.
AB  - According to the author, the assumption is made that in Meniere's disease,
      compensation should be paid in acoustic trauma cases. Meniere's disease is an
      aftereffect of noise exposure, even if the time lapse exceeds 10 years. A
      historical review of existing literature (from 1872 to 1958) shows no convincing
      evidence of this matter. Ten patients were chosen at random. All were exposed to
      noise and presented with vestibular dysfunction at a certain time.

PMID- 14689645
TI  - Noise exposure and its effect on the labyrinth, Part II.
AB  - The neurootological data of 12 patients attending our ear, nose, and throat
      clinic were analyzed. The patients submitted to a neurootological routine
      evaluation consisting of patient history recording and audiometric and
      equilibriometric investigations (i.e., electronystagmography). The conclusion was
      that many tinnitus patients--even those who had no vestibular symptoms--showed
      some disturbance in the vestibular tests, such as spontaneous and positional
      nystagmus and nystagmus alternans. Laurikainen came to the same conclusion in
      1995, after examining 10 patients with sudden deafness but no vestibular
      complaints. It is recommended that all patients with noise exposure, sudden
      deafness, and tinnitus of the severe disabling type undergo a complete
      cochleovestibular investigation.

PMID- 14689646
TI  - Falls in the elderly: the development of a risk questionnaire and posturographic
      findings.
AB  - In elderly people, owing to a perturbation at several levels, including the
      motor, sensory and cognitive levels, a condition of dizziness and unsteadiness
      complicated by frequent falls often appears. In this article, we review the most
      recent information about clinical and instrumental tools available for preventing
      mobility-related accidents and report the results of a comparative study of
      postural control, carried out through tetraataxiometry (by Tetrax, Tel Aviv,
      Israel), in two samples of elderly women belonging to two different populations:
      24 Italian women (11 reporting falls and 13 without falls) having a mean age of
      73.1 years, and 37 Israeli women (12 with falls and 25 without falls) having a
      mean age of 72.5 years. The posturographic findings show that the falling
      subjects, to maintain postural control, are highly dependent on somatosensory
      inputs and have a weaker "systeme postural fin" (fine postural system), according
      to Gagey. They also show that an elderly subpopulation exists that, for unknown
      reasons, is immune to destabilization and falls.

PMID- 14689647
TI  - Are demographic and socioeconomic factors predictive for perceived tinnitus
      impairment?
AB  - Patients suffering from chronic tinnitus were analyzed to examine whether
      tinnitus impairments can be predicted by demographic and socioeconomic factors.
      For this purpose, subjective tinnitus complaints were measured in 153 patients
      using the tinnitus impairment questionnaire (THI-12) that distinguishes between
      emotional-cognitive and functional-communicative factors. Age, gender, marital
      status, and education levels were assessed and treated as predictive variables.
      In computing canonical correlations, only the level of education served as a
      significant emotional-cognitive predictor for tinnitus impairment. Patients with
      lower education demonstrated impairments in the emotional-cognitive domain that
      were more marked than those in higher-educated people. The results indicated that
      demographic and socioeconomic variables have no predictive value for tinnitus
      impairments, with the exception of a person's level of education.

PMID- 14689648
TI  - Visuoocular reflexes in presbyvertigo.
AB  - Using electronystagmography, we tested 100 patients (ages 65-80 years)
      manifesting the clinical signs of presbyvertigo, for the purpose of demonstrating
      their visuoocular reflexes. We administered not only simple optokinetic and eye
      tracking stimuli but caloric modification of each one as well (with contrary
      directed optokinetic trace movement). The results were compared with those
      obtained in a group of 40 healthy subjects between the ages of 20 and 25 years.
      In the older group, we observed a statistically significant increased frequency
      of asymmetry of optokinetic nystagmus and pathological patterns revealed by the
      eye-tracking test and caloric modification of both the optokinetic and eye
      tracking tests. We discuss the hypothetical predominant localization of age
      dependent changes, with emphasis on the disturbances of visual-vestibular
      integration, on the basis of data obtained from anamnesis and other
      electronystagmographic findings.

PMID- 14689649
TI  - Special features of old age vertigo.
AB  - In daily clinical practice, it is seen that elderly patients complain most
      frequently of dizziness, tinnitus, and hearing loss. Listening to those
      complaints, do we not tend just to attribute them to age? Against this
      background, we review vertigo in elderly patients briefly and consider the key
      points of its treatment. In comparison to younger people, what is first
      noticeable about elderly people is that they have a lot of fat in the body and a
      markedly low level of intracellular water. In other words, elderly people are
      always at risk of dehydration and liable to enter a shock state. The dorsal root
      in the elderly is also degenerated, and this explains such diverse complaints as
      dizziness, tinnitus, ringing in the head, headache, neck and shoulder stiffness,
      and lumbago. However, these complaints cannot be dismissed simply as "an
      unidentified syndrome." Behind these complaints is invariably one or another
      organic disorder. This is the conclusion we have reached from our day-to-day
      clinical practice.

PMID- 14689650
TI  - Results of otovestibular tests in mild head injuries.
AB  - The neurotological workup of patients with minor head trauma was carried out
      prospectively. The preliminary results of the ongoing study were derived from 38
      subjects (12 female, 26 male) at an average age of 33.5 years. All had been
      hospitalized after having suffered minimum head trauma followed by a temporary
      loss of consciousness, by amnesia, or by vomitting. The 38 subjects underwent the
      examination within 72 hours of the event and were summoned for a follow-up visit
      3 months later. The anamnestic data show that the most frequent complaint was
      dizziness (81%). Tinnitus was noted in fewer than one-half of the patients, with
      a variety of descriptions. Twenty-six percent complained of hearing loss. The
      correlation between reported hearing loss and the finding on subsequent
      behavioral audiometry (within 72 hours after the event) was studied. The
      sensitivity of hearing loss (as complaint) was found to be only 40%, but its
      specificity was much higher at 83%. The overall equilibrium reflected in the
      composite score of the sensory testing in computed dynamic posturography actually
      worsened between tests. A good correlation was found between posturography
      results and symptomatology. We concluded that, after minor head trauma, most
      patients suffer from dizziness, and more than one-half complain of tinnitus or
      hearing loss. The unsteadiness does not subside within 3 months after concussion.
      A more protracted follow-up is required to summarize the outcome of head injury
      from a neurootological point of view. A clear correlation is found between
      complaints and posturography results. After minor head trauma, pure vestibular
      injuries are much less frequent than are central lesions. Motor dysfunction is
      less frequent than are the sensory abnormalities.

PMID- 14689652
TI  - Effects of orofacial myofunctional therapy on speech intelligibility in
      individuals with persistent articulatory impairments.
AB  - This study examined the effects of orofacial myofunctional therapy (OMT) on
      speech intelligibility in adults with persistent articulation impairments. Six
      adults in the age range of 18-23 years were selected to receive orofacial
      myofunctional therapy for a period of six weeks. The results showed that five out
      of six clients made significant progress in oral postures and speech sound
      production across all three speech production tasks: single words, sentences, and
      spontaneous speech. Speech intelligibility increased significantly in all clients
      except the one diagnosed with developmental apraxia of speech. Orofacial
      myofunctional therapists, speech-language pathologists, and other professionals
      need to rule out underlying orofacial myofunctional variables when targeting
      speech sounds for intervention. Speech production tasks may be considered as
      important measures to understand the efficacy of OMT in clinical settings.

PMID- 14689653
TI  - Oral structures and sleep disorders: a literature review.
AB  - In recent years, a wealth of studies revealed the many physiological and
      histological changes the oropharyngeal muscles go through as a result of sleep
      disorders, in particular, as a result of Obstructive Sleep Apnea (OSA). This
      article presents a literature review of the most recent findings regarding sleep
      disorders and their effect on oropharyngeal structures. The article includes
      classifications and definitions of various sleep disorders; explains the negative
      implications of sleep disorders in children, as well as in adults; reviews the
      viable options to treat sleep disorders; suggests steps in which the orofacial
      myologists could be instrumental in identifying and referring patients with
      possible sleep disorders; and suggests further studies on the subject conducted
      by orofacial myologists.

PMID- 14689651
TI  - Long-term inhibition of tinnitus by UltraQuiet therapy: preliminary report.
AB  - Masking of tinnitus by noise can produce residual inhibition, a persistence in
      the reduction in tinnitus after the noise is removed. Typically, this relief is
      very short-lived, on the order of minutes. This report highlights long-term
      inhibition of tinnitus by UltraQuiet therapy, a new technique that employs
      patterned sound in the 10- to 20-kHz range, presented through bone conduction.
      Nine subjects participated in a study of the efficacy of this tinnitus
      suppression technique. Eight reported improvement in tinnitus symptoms; one did
      not complete the study. The duration of the improvement ranged from days to
      weeks. This long-term inhibition may involve a truly plastic change in the brain
      at the central level.

PMID- 14689654
TI  - Cephalometric evaluation in children presenting adapted swallowing during mixed
      dentition.
AB  - The tongue trust and anterior projection through the dental arcades during
      swallowing is known as Adapted Swallowing (AS) and is a common finding during
      mixed dentition. The authors studied the morphologic dentofacial characteristics
      through cephalometric measures in 38 girls and 35 boys, aged seven to nine years,
      presenting AS, as determined by the speech therapist evaluation. Cephalometric
      evaluation was obtained by Radiocef 2.0 software. The measurements studied were
      the mandibular and maxillary relations to the cranial base, the nasolabial angle,
      and the upper airway patency, as proposed by McNamara Jr (1984), and the
      convexity and facial axis angles and maxillary height from Ricketts (1960; 1981).
      Results, analyzed in relation to sex and racial group, showed an association of
      Class II facial convexity with the African Brazilian children with dark black
      skin. This classification does not reflect an abnormality as all African
      Brazilians studied were classified as class II, due to the fact that the standard
      measurements are based in the white American population. These findings point to
      the need of specific racial normative standard for evaluating orofacial and
      dental structures.

PMID- 14689655
TI  - Lip sucking and lip biting in the primary dentition: two cases treated with a
      morphological approach combined with lip exercises and habituation.
AB  - Lip sucking and lip biting in the primary-dentition period can cause the upper
      incisors to tip labially and the lower incisors to collapse lingually with the
      lower lip wedged between the upper and lower anterior teeth. The resulting lip
      incompetence further aggravates maxillary protrusion. Thus, there is a causal
      relationship between lip sucking/lip biting and maxillary protrusion. Orofacial
      myologists provide lip training to activate the flaccid upper lip and raise the
      child's awareness to help stop the sucking or biting of the lower lip, sometimes
      using an oral screen. Two primary-dentition cases with lip sucking and lip biting
      were treated with a functional appliance (F.A.), resulting in the elimination of
      the habits in 5 to 6 months along with the improvement of the overjet, overbite
      and facial profile. The authors prioritize myofunctional therapy (MFT) when
      treating open bite cases with tongue thrust in the primary dentition. However,
      the treatment of maxillary protrusion due to lip sucking and lip biting is
      approached differently with priority given to morphological improvement to create
      an oral environment that makes lip sucking and lip biting difficult, which is
      complimented with lip exercises and habituation. This combined approach was found
      to be effective in breaking the lip-sucking and lip-biting habits.

PMID- 14689656
TI  - Power to the people.

PMID- 14689657
TI  - Idyll or nightmare?

PMID- 14689658
TI  - Hidden from history.

PMID- 14689659
TI  - White cells count.

PMID- 14689660
TI  - Nice and easy does it.

PMID- 14689661
TI  - Enquiring minds.

PMID- 14689662
TI  - Weights and measures.

PMID- 14689663
TI  - Nursing should carry a health warning.

PMID- 14689664
TI  - Racism and personal safety: black community practitioners.
AB  - BACKGROUND: The potential risks for and implications of black community
      practitioners working in racist areas is the subject of this article. It provides
      an overview of the risk of racial harassment and discusses the legal and ethical
      implications for NHS employees. This article has been written as a result of the
      author being confronted with the possibility of being sent to work in an area
      known to be racist. The British National Party's (BNP) recent gains in local
      elections demonstrate that such areas exist in the UK's towns and cities (BBC
      News 2003). CONCLUSION: The author argues that employers should do all in their
      power to benefit their employees and this means protecting them from working in
      racist areas or with racist clients who pose a potential risk.

PMID- 14689665
TI  - Supporting students with disabilities.
AB  - The use of workshops to inform and question practice is common. Two workshops on
      supporting learners with disabilities in the clinical environment are described
      with support from the literature. Examples of discrimination are outlined showing
      a wide variation in the NHS before the implementation of the Disability
      Discrimination Act 1995. Participants outlined barriers to learning in clinical
      environments and ways of overcoming those barriers. They also discussed the need
      to develop support mechanisms.

PMID- 14689666
TI  - Acquired brain injury: acute management.
AB  - Acquired brain injury is a non-degenerative brain injury that may affect anyone
      at any time. Patients with acquired brain injury are often critically ill and
      this injury can have a devastating and long-lasting effect on the patient's
      quality of life. Although hospital treatment cannot change the initial injury,
      good nursing care will help to limit and prevent secondary damage thus reducing
      the probability of long-term disability.

PMID- 14689667
TI  - Nurses expected to deliver on patient choice.

PMID- 14689668
TI  - Dying wishes.

PMID- 14689669
TI  - Creative care for older people.

PMID- 14689670
TI  - 'I'm delighted the new role is making a difference'.

PMID- 14689671
TI  - Legionellosis: epidemiology, management and prevention.
AB  - Legionellosis is an acute bacterial pneumonia, which is associated with a
      mortality rate of approximately 10-15 per cent in healthy individuals. It was
      first identified in the USA following an outbreak of pneumonia among delegates at
      a legionnaires' convention. Antibiotics provide effective treatment. Outbreaks
      continue to occur and have the most significant effects on older people and other
      vulnerable groups.

PMID- 14689673
TI  - Evaluation of the use of drama in sex and relationship education.
AB  - A programme of sex and relationship education was delivered in a comprehensive
      school in North Yorkshire by a theatre company. The programme was supported by a
      series of preparatory and follow-up workshops and was evaluated by a
      questionnaire before and after the intervention to measure changes in pupil's
      knowledge and attitudes. The evaluation found that the theatre production made a
      useful contribution to sex and relationship education. It also suggested
      improvements in the way the programme could be delivered.

PMID- 14689672
TI  - Patient-controlled analgesia after coronary artery bypass grafting.
AB  - Patient-controlled analgesia is a method of pain control that allows the patient
      to self-administer opioid medication as and when it is needed. Pain is a personal
      experience and one pain-relieving intervention may not be effective for all
      patients. This article reviews the literature on patient-controlled analgesia,
      particularly with reference to patients after coronary artery bypass grafting.
      Pain policies and education programmes need to be proactive in addressing staff
      and patient gaps in knowledge and misconceptions about pain assessment and
      management. Nurses need to appreciate the nature and importance of research in
      promoting a more critical approach to patient care and the development of quality
      nursing practice.

PMID- 14689674
TI  - What you need to know about ... chronic obstructive pulmonary disease.

PMID- 14689675
TI  - Simple coping strategies for people who hear voices.
AB  - High levels of stress are common among people who hear voices, but few receive
      help to cope with the problem. The reason for this appears to be that many mental
      health nurses are not aware that there are simple coping strategies that could be
      used to help these people. Some of these are explained in this article. They
      represent an example of providing person-centred care, which is at the centre of
      good mental health nursing.

PMID- 14689676
TI  - [IgA nephropathy, isolated hematuria and renal biopsy].

PMID- 14689677
TI  - [What are indications for surgery in patients with chronic mitral
      insufficiency?].

PMID- 14689678
TI  - [Chronic mitral regurgitation].

PMID- 14689679
TI  - [Streptokinase--yes or no--a black and white view].

PMID- 14689680
TI  - [Factor V Leiden and the Slovak population].
AB  - The resistance to activated protein C (APC-resistance) based on the presence of
      factor V Leiden (F V Leiden) is the most frequent thrombophilic condition in the
      white race population. It contributes to the origin of thrombosis especially in
      the venous part of blood vessels. Significant geographic differences have been
      detected within Europe. The aim of this retrospective study was to determine the
      frequency in the occurrence of F V Leiden: 1. in healthy (asymptomatic) Slovak
      population, 2. in their consanguineously unrelated members with thrombosis and 3.
      in patients with myocardial infarction (IM) without or with other known risk
      factors of this disease (nicotinism, obesity, hypertension, dyslipoproteinemia,
      diabetes mellitus), respectively. The detection of FV Leiden was made by
      molecular biology methods. The occurrence in a group of 152 healthy individuals
      was four % (6 persons) and this frequency corresponds to the geographic
      localization of the Slovak Republic in Europe. In a group of 349 patients with
      thrombosis in anamnesis, FV Leiden was detected in 103 persons (29.5%). The
      occurrence was higher than the usually reported incidence in these patients
      (20%). Likewise, in a group of 35 patients with IM without risk factors in
      anamnesis, the occurrence of FV Leiden (8.6%) was significantly higher in
      comparison with healthy population and the incidence further increased
      significantly in a group of 41 patients with IM and the presence of at least one
      risk factor (14.6%). The authors therefore suppose an active role of the Leiden
      mutation of FV gene in the pathogenesis of this disease.

PMID- 14689681
TI  - [Comprehensive care of drug addiction during a 5-year period at the methadone
      center in Prague].
AB  - Methadone maintenance program in General Faculty Hospital in Prague has been in
      operation for five years since August 1997. During this period a broad spectrum
      of complex care was supported to opioid drug addicts. Not only substitution of
      methadone or buprenorphine but also psychiatric, social and health care was
      guaranteed. The goal of this article is the information about our experience
      achieved during the five-year existence of the methadone maintenance program.

PMID- 14689682
TI  - [Desirable and undesirable effects of thalidomide in patients with multiple
      myeloma].
AB  - Thalidomide, an antiemetic administered in 60th of the 20th century to pregnant
      women, has become notorious for a range of adverse effects which led to its
      taking off market. In recent years, its antimyeloma effect was discovered. The
      aim of the work was to evaluate the incidence of adverse reactions to
      thalidomide. Its therapeutic effect has not been assessed because of a short
      period of monitoring and diversity of a sample. The assessed sample consisted of
      17 patients with diagnosis of multiple myeloma (10 men and 7 women). An average
      age of patients was 62.9 +/- 9.4. An average time elapsed from making the
      diagnosis to starting the treatment with thalidomide was 51.0 +/- 23.7 months. An
      average length of therapy was 20.1 +/- 9.6 weeks. An average daily maximum
      therapeutic dose was 138.3 +/- 83.2 mg. Data were collected from outpatient
      physicians reports, regular laboratory tests, and direct interviews with
      patients. To classify severity of adverse drug effects (grades 0-4) we used WHO
      criteria, Cancer and Leukemia Group B criteria, and in cases where certain
      adverse effects were not included in the above mentioned criteria, we defined our
      own criteria. The most frequent adverse effects included: leucopenia or
      neutropenia in 12 (70.6%) patients, altered state of consciousness in 11 (64.7%)
      patients, obstipation in 10 (58.8%) patients, skin alterations in 9 (52.9%)
      patients, dizziness in 8 (47.1%) patients, peripheral neuropathy in 7 (41.2%)
      patients, spasms and spasmodic convulsions in 7 (41.2%) patients, and altered
      liver tests in 6 (35.3%) patients. From the perspective of necessity to interrupt
      treatment or reduce the dose the most severe disorders included: peripheral
      neuropathy in 2 patients (inability to control lower extremities), altered
      consciousness in 1 patient (protracted somnolence during a day), skin alteration
      in 1 patient (generalized toxoalergic reaction), leucopenia or neutropenia in 1
      patient (1.0 resp < 0.5 x 10(9)/l), altered vision in 1 patient (blurred vision),
      hypothyroidism in 1 patient, and altered mood in 1 patient (subjective feeling of
      depression). This work proved thalidomide to be beneficial for the patients with
      multiple myeloma but it also shoved necessity to intensively monitor its adverse
      effects and to adjust its doses.

PMID- 14689683
TI  - [IgA nephropathy. Use of modern laboratory methods and renal biopsy for
      diagnosis].
AB  - IgA nephropathy is the most frequent primary glomerulonephritis worldwide. At its
      onset, the most common laboratory sign is isolated haematuria often accompanied
      with mild proteinuria (up to 1.5 g/24 h). The disease displays a progressive
      course with end-stage renal disease occurring in up to half of patients 20 years
      after onset. Diagnosis is established by immunofluorescent microscopy of a renal
      biopsy specimen. Discoveries in the past decade on the pathogenesis of IgA
      nephropathy together with complex evaluation of its clinical presentation enable
      to establish diagnosis with a satisfactory degree of probability even without
      biopsy. IgA nephropathy patients display increased or borderline serum IgA
      levels; increased serum levels of IgA fraction with degalactosylated O-linked
      side sugar chains; increased serum levels of anti-N-acetylgalactosamine
      antibodies; increased levels of circulating immune complexes composed of IgA1
      complexed with IgG or IgA1; increased serum levels of circulating complexes
      composed of IgA and fibronectin; and frequent occurrence of the rheumatoid IgA
      factor. Clinical use of these still generally unavailable methods would reduce
      the renal biopsy indication in patients with isolated or predominant haematuria.

PMID- 14689684
TI  - [What are indications for surgery in patients with chronic mitral
      regurgitation?].
AB  - This review has been aimed at the presentation of present etiological spectrum of
      mitral regurgitation and its natural course. A basal survey of pathophysiology of
      this complicated and insidious defect, which should help to understand its
      clinical and hemodynamic classification, is presented. The developmental phases,
      characterized by very long asymptomatic period, when the heart function is
      compensated and the prognosis is good, are outlined. However, as a paradox of
      this defect, the contractile function of the left ventricle is damaged as early
      as in the compensation phase in spite of normal value of the ejection fraction.
      In the advanced phase the defect threatens that the carrier may suddenly die.
      Basic methods of quantification are presented as well as their principles. The
      development cardiosurgical techniques, which enable reconstruction of the mitral
      valve, and very good long-term and short-term results in large cohorts
      significantly influenced indication criteria. The causes of increasing interest
      in surgical treatment of mitral regurgitation, which is aimed at maintaining the
      inotropic function of myocardium and improvement of quality and duration of life,
      are presented. A successful mitral reconstruction, often connected with
      modification of the left atrium function, is associated with lower post-operation
      mortality, higher resistance of the native valve against infectious endocarditis
      and very frequently maintaining sinus rhythm as well. The review draws attention
      of wider medical audience, especially general physicians and general internal
      physicians, to the present possibilities of cardiosurgical treatment of mitral
      regurgitation. The therapy of mitral regurgitation is dramatically changing and
      the indication shift to markedly earlier stages.

PMID- 14689685
TI  - [Does streptokinase still have a role in the treatment of acute myocardial
      infarct?].
AB  - Streptokinase was discovered in 1933. Its importance has gradually grown since
      1950's of the last century when it was used as the utterly first thrombolytic
      agent. Since the discovery that majority of acute myocardial infarctions is
      caused by thrombus in the area of ruptured endothel above the atherosclerotic
      platelet, it has become the first remedy able of real causal treatment of acute
      myocardial infarction (AMI). These days it becomes an obsolete remedy because of
      a range of disadvantages. Neutralizing antibodies for instance remain in organism
      for many years after its administration, which results in an inefficacious
      treatment. Moreover it causes allergic reactions or anaphylaxis in a part of
      population, hypotension, and decrease of its fibrinolytic effect after more then
      3 hours after development of AMI. The most problematic is its anticoagulant
      effect lasting more than 24 hours after its administration and simultaneous
      increase in prothrombotic activity, which is a disadvantage if intervention
      treatment methods are appropriate (direct coronary angioplasty). The only
      advantage of streptokinase is its relatively low price. However, it cannot
      justify its use as a thrombolytic agent of the first choice and it is high time
      for it to be replaced in its treatment indications by plasminogen activator or by
      thrombolytic agents of the third generation derived from it, which can be
      conveniently administered in the bolus form.

PMID- 14689686
TI  - Case reports and review of Postural Orthostatic Tachycardia syndrome (POTS).
AB  - Postural Orthostatic Tachycardia Syndrome (POTS) is a type of orthostatic
      intolerance that is characterized by excessive tachycardia and decreased cerebral
      blood flow in the upright position. This can result in significant symptoms of
      dizziness and light-headedness that can eventually lead to syncope. In this
      review, we describe two patients with POTS that varied in their degree of
      symptoms and treatment. One patient was able to be treated as an outpatient,
      while the other required hospitalization and extensive medical therapy. We would
      like to emphasize with this review that POTS is probably more common than it is
      diagnosed and is often confused with other conditions, such as chronic fatigue
      syndrome or functional syncope. It is important to make the correct diagnosis in
      order to allow appropriate treatment and to improve the quality of life for these
      patients.

PMID- 14689687
TI  - Nurturing our resources.

PMID- 14689689
TI  - Preface to volume 60 the flaviviruses: pathogenesis and immunity.

PMID- 14689688
TI  - Preface to the flaviviruses.

PMID- 14689690
TI  - Molecular determinants of virulence: the structural and functional basis for
      flavivirus attenuation.

PMID- 14689691
TI  - Genetic resistance to flaviviruses.
AB  - Resistance to flavivirus-induced disease in mice was first discovered in the
      1920s and was subsequently shown to be controlled by the resistant allele of a
      single dominant autosomal gene. While the majority of current laboratory mouse
      stains have a homozygous-susceptible phenotype, the resistant allele has been
      found to segregate in wild mouse populations in many different parts of the
      world. Resistance is flavivirus specific and extends to both mosquito- and tick
      borne flaviviruses. Resistant animals are infected productively by flaviviruses
      but produce lower virus titers, especially in their brains, as compared to
      susceptible mice. Decreased virus production is observed in resistant animals
      even during a lethal infection and the times of disease onset and death are also
      delayed as compared to susceptible mice. An intact immune response is required to
      clear flaviviruses from resistant mice. The resistant phenotype is expressed
      constitutively and does not require interferon induction. The Flv gene was
      discovered using a positional cloning approach and identified as Oas1b.
      Susceptible mice produce a truncated Oas1b protein. A C820T transition in the
      fourth exon of the gene introduced a premature stop codon and was found in all
      susceptible mouse strains tested. Possible mechanisms by which the product of the
      resistant allele could confer the resistant phenotype are discussed.

PMID- 14689692
TI  - Immunobiology of mosquito-borne encephalitic flaviviruses.

PMID- 14689693
TI  - Immune modulation by flaviviruses.
AB  - Flaviviruses cause pleomorphic disease with significant morbidity and mortality
      worldwide. Interestingly, in contrast to most viruses, which subvert or avoid
      host immune systems, members of the neurotropic Japanese encephalitis serocomplex
      cause functional changes associated with increased efficacy of the immune
      response. These viruses induce increased cell surface expression of immune
      recognition molecules, including class I and II major histocompatibility complex
      (MHC) and various adhesion molecules. Increases are functional: infected cells
      are significantly more susceptible to both virus- and MHC-specific cytotoxic T
      cell lysis. Induced changes are modulated positively or negatively by Th1 and Th2
      cytokines, as well as by cell cycle position and adherence status at infection.
      Infection also increases costimulatory molecule expression on Langerhans cells in
      the skin. Local interleukin-1 beta production causes accelerated migration of
      phenotypically altered Langerhans cells to local draining lymph nodes, where
      initiation of antiviral immune responses occur. The exact mechanism(s) of
      upregulation is unclear, but changes are associated with NF-kappa B activation
      and increased MHC and ICAM-1 gene transcription, independently of interferon
      (IFN) or other proinflammatory cytokines. Increased MHC and adhesion molecule
      expression may contribute to the pathogenesis of flavivirus encephalitis. Results
      from a murine model of flavivirus encephalitis developed in this laboratory
      suggest that fatal disease is immunopathological in nature, with IFN-gamma
      playing a crucial role. We hypothesize that these viruses may decoy the adaptive
      immune system into generating low-affinity T cells, which clear virus poorly, as
      part of their survival strategy. This may enable viral growth and immune escape
      in cycling cells, which do not significantly upregulate cell surface molecules.

PMID- 14689694
TI  - Mechanisms of dengue virus-induced cell death.
AB  - The outcome of virus infection depends on viral and host factors. The
      interactions between flaviviruses and their target cells must be investigated if
      we are to understood the pathogenicity of these RNA viruses. Host cells are
      thought to respond to viral infection by initiation of apoptotic cell death.
      Apoptosis is an active process of cellular self-destruction with distinctive
      morphological and biochemical features. There is mounting evidence that dengue
      (DEN) virus can trigger the host cell to undergo apoptosis in a cell-dependent
      manner. Virally induced apoptosis contributes directly to the cytopathogenic
      effects of DEN virus in cultured cells. The induction of apoptosis involves the
      activation of intracellular signaling systems. Although the underlying molecular
      processes that trigger apoptosis are not well characterized, our knowledge
      regarding the cellular mechanisms and viral determinants of the outcome of DEN
      virus infection of target cells is improving. The cellular factors that regulate
      cell death, such as Bcl-2 family members, can modulate the outcome of DEN virus
      infection in cultured cells. Apoptosis inhibitors delay DEN virus-induced
      apoptosis, thereby providing a suitable environment for the virus. During DEN
      virus infection, cell death is also modulated by the virulence of the infecting
      strains. The purpose of this review is to present recent information on the
      cellular mechanisms and viral proteins associated with apoptosis in response to
      DEN virus. This knowledge may provide new insights into the viral pathogenicity.

PMID- 14689695
TI  - Dynamics of flavivirus infection in mosquitoes.

PMID- 14689696
TI  - Dynamics of infection in tick vectors and at the tick-host interface.
AB  - Tick-borne flaviviruses are common, widespread, and successfully adapted to their
      mode of transmission. Most tick vectors of flaviviruses are ixodid species. These
      ticks are characterized by a comparatively long life cycle, lasting several
      years, during which the infecting virus may be maintained from one developmental
      stage of the tick to the next. Hence ticks act as highly efficient reservoirs of
      flaviviruses. Many tick-borne flaviviruses are transmitted vertically, from adult
      to offspring, although the frequency is too low to maintain the viruses solely in
      the tick population. Instead, the survival of tick-borne flaviviruses is
      dependent on horizontal transmission, both from an infected tick to a susceptible
      vertebrate host and from an infected vertebrate to uninfected ticks feeding on
      the animal. The dynamics of transmission and infection have traditionally been
      considered in isolation: in the tick, following virus uptake in the infected
      blood meal, infection of the midgut, passage through the hemocoel to the salivary
      glands, and transmission via the saliva; and in the vertebrate host, virus
      delivery into the skin at the site of tick feeding, infection of the draining
      lymph nodes, and dissemination to target organs. However, there is now compelling
      evidence of a complex interaction between the tick vector and its vertebrate host
      that affects virus transmission profoundly. The feeding site in the skin is a
      battleground in which the hemostatic, inflammatory, and immune responses of the
      host are countered by antihemostatic, anti-inflammatory, and immunomodulatory
      molecules (mostly proteins and peptides) secreted in tick saliva. Here we
      speculate that exploitation of the tick pharmacopeia, rather than development of
      viremia, is the key step in successful tick-borne flavivirus transmission.

PMID- 14689697
TI  - Pathogenesis of flavivirus encephalitis.

PMID- 14689698
TI  - Pathogenesis and pathophysiology of yellow fever.
AB  - It will be apparent to the reader that there is much to learn about the
      pathogenesis of YF. The role of specific genes and molecular determinants of
      neurotropism and viscerotropism has been defined only partially. The availability
      of infectious clones and a small animal (hamster) model should allow dissection
      of virulence factors, which can then be tested in the more difficult monkey
      model. The marked differences between wild-type YF strains should be evaluated by
      evaluating the relationships between virulence and genome sequence. The role of
      cytokine dysregulation and endothelial injury in YF will be elucidated as access
      to patients and of patients to more sophisticated medical care improves. The
      number of cases of YF in unvaccinated travelers hospitalized after return from
      the tropics has unfortunately increased, but such cases afford unique
      opportunities to study the pathogenesis of renal failure, coagulopathy, vascular
      instability, and shock, as well as new treatment modalities. At the cellular
      level, there are also important opportunities for research on YF virus-cell
      receptor interactions, the control of apoptotic cell death, and the predilection
      for cells of the midzone of the liver lobule. The role of dendritic cells in the
      early stage of YF infection is deserving of study. Finally, the role of the
      immune response to infection, particularly cellular immunity, is poorly
      characterized, and the suggestion that immune clearance may aggravate the
      condition of the host during the period of intoxication should be evaluated in
      appropriate animal models.

PMID- 14689699
TI  - Immunology and immunopathogenesis of dengue disease.
AB  - The pathophysiological basis of severe dengue disease (i.e., dengue hemorrhagic
      fever [DHF]), appears to be multifactorial, involving complex interactions among
      viral factors, host genetics, and the immunologic background of the host,
      principally prior exposure to dengue virus. Analysis of these processes has been
      limited to observational studies of naturally infected humans because there have
      not been useful animal models of dengue disease. Substantial evidence points to
      dengue virus-reactive T cells as a critical effector in the development of DHF.
      We are beginning to define the critical elements of T-cell epitope specificity
      and functional responses that contribute to DHF. Additional studies in well
      characterized patient cohorts from different geographic regions will be needed to
      advance this research and guide new approaches to prevention and treatment of
      DHF.

PMID- 14689700
TI  - Neutralization and antibody-dependent enhancement of dengue viruses.

PMID- 14689701
TI  - [Impairment of cardiovascular function in subclinical hypothyroidism].
AB  - Subclinical hypothyroidism (SH) is the most frequent thyroid disease, but
      administration of replacement L-thyroxin in it is not obvious. SH may present
      both with general nonspecific symptoms and disturbance of lipid metabolism,
      myocardial dysfunction. Many physicians think it valid to restore euthyroid
      condition, as it may improve general condition of the patients, diastolic and
      systolic myocardial function, prognosis in ischemic heart disease. However, there
      are no definite indications to starting L-thyroxin in SH.

PMID- 14689702
TI  - [Primary ciliary dyskinesia: an attempt at classification of mucociliary
      clearance disorders (analysis of literature and original data)].
AB  - The article presents a review of literature and original data on diagnosis of
      genetically determined pathology of the lungs--primary ciliary dyskinesia.
      Clinical, functional-morphological and genetic aspects are considered. A
      classification is proposed of dysfunction of mucociliary clearance.

PMID- 14689703
TI  - [Effects of monotherapy with an alpha1-adrenoblocker doxazosin and its
      combination with beta1-adrenoblocker atenolol on hemodynamics, reversible
      myocardial ischemia in postmyocardial infarction patients with arterial
      hypertension].
AB  - Effects of doxasozine and atenolol on hemodynamics and myocardial ischemia were
      studied in 20 males (mean age 52.5 +/- 5.3 years) who had survived macrofocal
      myocardial infarction associated with arterial hypertension stage I-II. The
      treatment efficacy was assessed clinically, by functional and radionuclide tests.
      A new long-acting alpha 1-adrenoblocker doxasozine was given in a mean dose 4-8
      mg/day. A course of this treatment lowered systolic arterial pressure by 8.3% and
      diastolic one by 8.1%. As all the patients developed sinus tachycardia on day 5
      10 of doxasozine treatment, the patients received additionally beta 1
      adrenoblocker atenolol (12.5-25 mg/day) which adequately controlled heart rate.
      The combined therapy reduced frequency and severity of angina by 34.7%, 24-h need
      in nitroglycerine by 37.9%, exercise tolerance--by 18.4% as well as improved
      myocardial perfusion. Patients with concomitant benign prostatic hyperplasia
      showed attenuation of disuric disorders. Side effects (vertigo, anxiety) occurred
      in 3 cases (15%), but were not severe enough to demand the treatment
      discontinuation.

PMID- 14689704
TI  - [Phenomenon of myocardial ischemia in patients with essential arterial
      hypertension with unaffected coronary arteries].
AB  - Cause-effect relationships (CER) between development of ischemia and ischemic
      damage to hypertrophic myocardium were studied in 128 hypertensive patients (23
      females, 105 males aged 35 to 58 years, mean age 52.3 +/- 1.2 years). CER were
      assessed basing on clinical condition of the patient, results of functional
      stress tests (transesophageal atrial pacing-TAP), Holter ECG and arterial
      pressure monitoring, changes in serum myoglobin levels. The analysis of
      correlations between development of left-ventricular myocardial hypertrophy,
      frequency and duration of painless ischemic episodes, severity of ischemic damage
      has established that duration of painless ST depression directly and
      significantly correlated with left ventricular myocardial mass (r = 0.88, p <
      0.01). It was found that hypertensive patients with elevated serum myoglobin and
      its normal values differed significantly both by after-TAP number of episodes of
      painless ST depression (12.5 +/- 2.69 vs 5.66 +/- 0.86; p < 0.002) and by their
      duration (4.1 +/- 1.02 min vs 2.45 +/- 0.41 min, respectively; p < 0.001).
      Clinical implications of elevated concentration of serum myoglobin in
      hypertensive patients with unaffected coronary arteries were defined.

PMID- 14689705
TI  - [Prognostic value of elevation of plasma concentration of atrial natriuretic
      peptide in patients with cardiac failure. Results of a cohort study].
AB  - A total of 172 patients with cardiac failure (CF) of functional class II-IV aged
      46-62 years were studied. Clinical condition of the patients was stabilized by
      the conventional therapy including ACE inhibitor--enalapril in a dose 10-20
      mg/day. In 3 weeks this therapy was combined with losartan in a dose 25-50
      mg/day. The course of treatment was 48 weeks. Cardiodynamics was assessed by
      duplex echocardiography and dopplerography. Plasmic concentrations of atrial
      sodiumuretic peptide (ASUP), renin, angiotensin-II, aldosteron, norepinephrine,
      epinephrine, serotonin, hydrocortisone, endothelin-1 were measured with
      radioimmunoassay. In the study group there were 31 deaths for 48 weeks. ASUP
      concentration in the deceased was significantly higher than in the survivors (n =
      141). The stepwise regression analysis discovered correlation between plasmic
      ASUP and end-diastolic volume of the left ventricle (r = 0.62; p = 0.01),
      dopplerographic index (r = 0.52; p = 0.001), left ventricular ejection fraction
      (r = -0.66; p = 0.002), velocity of early diastolic filling (r = -0.84; p =
      0.001), plasmic pool of norepinephrine (r = 0.66; p = 0.001), endotheline-1 (r =
      0.70; p = 0.03) and angiotensin-II (r = 0.55; p = 0.02), daily dose of furosemide
      (r = 0.80; p = 0.001), heart rate (r = 0.64; p = 0.02). The strongest negative
      effect on CF patients' survival was linked with plasmic content of ASUP (relative
      risk = 4.55), angiotensin-II (RR = 3.2), ejection fraction < 25% (RR = 3.02).
      Thus, elevation of ASUP in blood plasm can be regarded a marker of a high
      cardiovascular risk of CF patients treated with AT-antagonist.

PMID- 14689706
TI  - [Phototherapy of hemorheological disorders in coronary failure].
AB  - Blood rheology (viscosity of the whole blood and plasm, hematocrit and fibrinogen
      concentration) was studied in 34 anginal inpatients. All the above indices were
      found elevated. Medication in 16 patients was combined with photopherapy (PT)-
      extracorporeal autoblood exposure to blue light (BL). 8 patients' blood was
      exposed to UV-radiation. Only BL PT produced a positive effect on blood viscosity
      due, primarily, to hematocrit reduction.

PMID- 14689707
TI  - [Psychosomatic correlations and autonomic regulation of functions in peptic ulcer
      in inhabitants of the European North of the Russian Federation].
AB  - The study of 71 patients with ulcer disease has found correlations between
      psychological status (personality and reactive anxiety, neurotism, type of
      personality response to the disease) and many clinical symptoms of the disease.
      Autonomic regulation features in ulcer citizens of the European North,
      correlations between vegetative tone and psychological status of the patients are
      characterized.

PMID- 14689708
TI  - [Hypoxic therapy of arterial hypertension in patients with different variability
      of arterial pressure].
AB  - Sixty two patients with essential hypertension stage II were divided into two
      groups. 32 patients of group 1 received combined therapy including a course of
      inhalations of gas hypoxic mixture containing 10% oxygen and conventional
      medication (ACE inhibitors, beta-blockers, calcium antagonists, diuretics). 30
      patients of group 2 (controls) were given medication alone. 24-h monitoring of
      arterial pressure (AP) and echocardiography suggested that high AP variability
      (APV) in hypertensive subjects leads to more significant changes in left
      ventricular and atrial structure and function typical for hypertensive heart. In
      high VAP, its night values are subnormal while daytime values are high in
      patients on combined medication and hypoxic therapy. The patients on standard
      medication had significantly low VAP at night while their daytime VAP tended to
      decrease. VAP positively correlated with hypertensive load. In high VAP hypoxic
      and drug therapies are less effective.

PMID- 14689709
TI  - [A 24-hour profile of arterial pressure: vegetative regulation in persons with
      isolated systolic arterial hypertension].
AB  - A total of 117 persons were studied: 60 patients with isolated systolic arterial
      hypertension (ISAH) (22 males, 38 females; mean age 68.7 +/- 4.2 years), 22 males
      with ISAH (mean age 20.1 +/- 2.7 years), 15 healthy elderly subjects and 20
      healthy young males. The analysis of heart rhythm variability and the results of
      24-h arterial pressure monitoring specified an individual 24-h profile of
      arterial pressure and effects of vegetative regulation on this profile.

PMID- 14689710
TI  - [Arterial hypertension and ischemic heart disease: clinico-echocardiographic
      aspects].
AB  - Doppler M-mode echocardiography was made in 156 males with ischemic heart disease
      (IHD) verified coronarographically. The patients were normotensive or had mild,
      moderate and severe arterial hypertension (AH) (groups 1, 2, 3 and 4,
      respectively). The groups were similar by functional anginal class.
      Echocardiographic findings were in many cases similar. This supports the
      hypothesis that IHD and AH are closely related. However, the addition of AH to
      atherosclerotic affection of the coronary artery or atherosclerosis rise in the
      presence of AH is associated with development of myocardial hypertrophy which is
      registered at echocardiography and correlates in severity with severity of AH.
      Myocardial hypertrophy is, on the one side, compensatory as it prevents dilation
      of the left ventricle and impairment of its contractility rising at later stage
      of the disease with depletion of the myocardial and coronary reserves, but, on
      the other side, it promotes diastolic dysfunction of the left ventricle, lowers
      its performance. The above phenomena are most pronounced in combination of IHD
      with severe AH. This combination presents a new qualitative state and, therefore,
      needs new approaches to its correction.

PMID- 14689711
TI  - [Optimization of sanatorium treatment of patients with essential hypertension
      stage II by chronotherapy].
AB  - A comprehensive chronodiagnostic examination and treatment were performed in 45
      patients with essential hypertension stage II aged 37 to 68 years taking 21-day
      treatment at sanatorium Osetia. The patients were divided into 2 groups: 20
      patients of group 1 received basic antihypertensive treatment (enap,
      hypothiaside) and sulfurated hydrogen balneotherapy not adjusted to individual
      biorhythm; 25 patients of group 2 received the same treatment by adjusted to
      biorhythmic phases of basic cardiovascular indices and chronotype established
      according to Estberg's questionnaire. Estimation of the rhythms of the integral
      indices of physiological functions (systolic and diastolic arterial pressure,
      heart rate, body temperature) and "individual minute" was made within 3 days in 4
      h intervals. Hemodynamics was studied before and in the end of the treatment with
      echocardiography, dopplerechocardiography and rheoencephalography. Positive
      shifts were registered in both groups: a significant fall in arterial pressure,
      total peripheral vascular resistance, double product and cardiac performance.
      Patients of group 2 had greater number of significant rhythms of physiological
      function parameters, primarily circadian, more frequent recovery of amplitude and
      phase parametric characteristics, better improvement of cerebral circulation,
      contractile and diastolic functions of the myocardium, reduction of the required
      medication doses and 2-fold lowering of side effects rate.

PMID- 14689713
TI  - [Nitrates in therapy of effort angina in hypotensive patients].
AB  - A randomized single blind cross-over trial with placebo lead-in has been
      conducted in 71 anginal patients with arterial hypotension (group 1) and 38
      ischemic heart disease patients with normal arterial pressure (group 2) to
      compare efficacy of therapy with isosorbide dinitrate (ID), sustac-forte (SF),
      isosorbide dinitrate retard (IDR) and trinitrolong (TN). Paired bicycle exercises
      revealed that in group 1 patients ID was low effective in 49%, SF--in 61%, IDR
      was highly effective in 97% and TN--in 96%. In group 1 tolerance to antianginal
      effect of ID, SF and IDR shown by stress myocardial scintigraphy with Tl-199
      developed earlier--in 2-4 weeks in 63-70% patients (versus 22-27% in group 2; p <
      0.01). Recovery of ID, SF, IDR effect required prolongation of the drug
      withdrawal period to 8-16 days (versus 3-5 days in group 2; p < 0.05). TN therapy
      remained effective for 3 months. Resistance to ID, SF in group 1 was relative and
      depended on dosage form of nitrates.

PMID- 14689712
TI  - [Assessment of anti-arrhythmic efficacy of a domestic drug allapinin in patients
      with ischemic heart disease and cardiac arrhythmia].
AB  - Antiarrhythmic activity of oral allapinin was studied in 64 patients with
      ischemic heart disease. 27 of the patients had undergone coronary artery bypass
      grafting 2 to 12 months before, 19 patients had postinfarction cardiosclerosis,
      38--arterial hypertension, 30--circulation insufficiency stage I. Arrhythmia
      presented as ventricular extrasystole (n = 28), paroxysmal atrial fibrillation (n
      = 18), paroxysmal atrial tachycardia (n = 11), frequent supraventricular
      extrasystole (n = 7). Arrhythmia continued from 6 months to 8 years. An effective
      single dose was defined with acute pharmacological test. The treatment course
      lasted for 21 days. Allapinin proved to be highly effective: ventricular ectopic
      activity was suppressed in 71.4% patients, atrial tachycardia paroxysms were
      prevented in 72.7%, paroxysms of atrial fibrillation--in 77.8%. Allapinin
      tolerance was good. Extracardiac side effects occurred most frequently, but dose
      lowering was necessary only in 6.2%. The drug was discontinued because of cardiac
      side effects in 4.7% cases. ECG monitoring is a highly informative method of the
      treatment efficacy control.

PMID- 14689714
TI  - [Experience in the use of immunomodulator likopid in ulcer disease].
AB  - We studied the effect of immunomodulator likopid on leukocytic immunity and
      duodenal ulcer (DU) course in 92 DU patients (70 males, 22 females; mean age 32
      +/- 1.2 years) having positive tests for Helicobacter pylori. The diameter of
      ulcer defects in the duodenal bulb ranged from 0.2 to 1.3 cm, mean size of ulcer
      was 0.8 +/- 0.1 cm. We measured lymphocyte population with rosette formation
      test, T-lymphocyte subpopulation by determination of sensitivity to teophylline,
      humoral immunity--with Manchini. The addition of likopid to present-day antiulcer
      therapy with antisecretory and antihelicobacter drugs shortens ulcer healing by 3
      4 days, raised H. pylori eradication to 100%. In the course of the treatment
      lymphocyte and monocytes count increased, neutrophil count reduced. The course
      treatment normalized cellular immunity: count of T-lymphocytes rose to 1.27 x
      10(9) +/- 0.01 to 1.78 x 10(9) +/- 0.04 g/l (p < 0.05), T-suppressors--from 11.36
      +/- 0.56 to 14.05 +/- 0.52% (p < 0.05), count of B-lymphocytes fell from 32.44 +/
      0.31 to 28.7 +/- 0.28%. A positive trend in the number of T-lymphocytes was
      accompanied with normalization of T-helpers/T-suppressors which increased from
      2.51 +/- 0.21 to 3.52 +/- 0.18 (p < 0.01). CIC tended to lowering from 118.1 +/-
      0.43 to 110.6 +/- 0.27 U (p < 0.05). Complement concentration in the serum rose
      from 30.1 +/- 0.3 to 32.6 +/- 0.2 (p < 0.001). This improved DU course. Thus,
      inclusion of likopid improves immune status of the patients, free radical
      oxidation of lipids and, consequently shortens ulcer healing.

PMID- 14689715
TI  - [Clinical efficiency of prognostic rules in patients with nonhospital pneumonia].
AB  - We studied efficacy of predicting outcomes of the disease in 345 patients (mean
      age 48.3 +/- 4.5 years) with extra hospital pneumonia (EHP). The risk of an
      unfavourable outcome was determined according to three prognostic rules (PR) of
      the British Thoracic Society. Ambiguity of the results necessitates specification
      of the PR indicators' prognostic value in respect to age and social aspects while
      PR assessment of the disease severity can serve an important tool in perfection
      of care for EHP patients.

PMID- 14689716
TI  - [Alcohol pathology in a general hospital].
AB  - Screening of chronic alcohol intoxication (CAI) based on parallel use of test
      questionnaires (CAGE, PAS-questionnaire) and assessment of organic evidence of
      alcohol abuse were employed in a clinicoepidemiological case-control survey
      covering 1191 patients aged 16-91 years admitted to a general hospital. 3335
      autopsy protocols were analysed by pathoanatomical and forensic-medical criteria
      of CAI. It was found that CAI, directly or indirectly, raises risk of a wide
      spectrum of internal diseases which, according to ICD-10, are not directly
      related to alcohol. Each 5th hospitalization was caused by CAI sequela. Combined
      use of tests-questionnaires and consideration of physical stigms of CAI are
      proposed for screening of alcohol abuse and latent alcoholism in general medical
      practice. The authors think it necessary to establish addictological service at
      large general hospitals.

PMID- 14689717
TI  - [Deontological education of students in the Internal Medicine Department].

PMID- 14689718
TI  - Another approach to hip fracture prevention.

PMID- 14689719
TI  - CT and nodules revisited.

PMID- 14689720
TI  - Taming the malpractice wildfire. Physicians, patients, and the public can cool
      the flames of litigation.

PMID- 14689721
TI  - Evaluation of obesity. Who are the obese?
AB  - Obesity has become increasingly prevalent in westernized countries, and in the
      United States it has reached epidemic proportions. The risks linked to obesity-
      such as cardiovascular disease, hypertension, and type 2 diabetes--make this
      condition one that deserves time and recognition by primary care physicians.
      Here, Dr Bray reviews the characteristics that define overweight and obesity, the
      factors that contribute to the pathogenesis of obesity, and current approaches to
      its management.

PMID- 14689722
TI  - Future directions in weight control. Molecular and genetic discoveries pave the
      way.
AB  - Obesity is the result of a long-standing imbalance between energy intake and
      energy expenditure, aided by a complex biologic system that regulates appetite
      and favors intake. New knowledge about substances that stimulate or inhibit
      appetite offers hope that drug-based solutions will be found for the current high
      prevalence of obesity in the United States. In this article, Dr Bessesen
      highlights some of the new molecular and genetic discoveries related to obesity
      and outlines the hypothalamic neural pathways involved in regulating food intake.

PMID- 14689723
TI  - C-reactive protein as a novel biomarker. Reactant can flag atherosclerosis and
      help predict cardiac events.
AB  - C-reactive protein (CRP) is a relatively nonspecific marker of inflammation.
      However, it can be used to monitor the severity and progression of some well
      defined cardiovascular diseases. For example, it can predict serious events in
      patients with coronary artery disease (CAD) who are hospitalized with acute
      coronary syndrome, myocardial infarction (MI), or advanced peripheral vascular
      disease. In this article, the authors review the role of CRP in the diagnosis,
      monitoring, and treatment of various forms of ischemic and inflammatory
      cardiovascular disease.

PMID- 14689724
TI  - How to monitor during testosterone replacement therapy?

PMID- 14689725
TI  - Patient notes: interstitial cystitis.

PMID- 14689726
TI  - [Sensitivity of cholinesterases from various sources to organophosphate
      inhibitors with S-alkyl radicals of various lengths].

PMID- 14689728
TI  - [Adaptive changes in the rate of oxygen consumption and lipid metabolism by
      Littorina saxatilis during parasitic invasion].

PMID- 14689727
TI  - [Unproductive substrate binding as one aspect of substrate specificity of
      cholinesterases of different adhesiveness].

PMID- 14689729
TI  - [Proteolytic activity of microflora associated with digestive intestinal surface
      transportation of burbot Lota lota parasitized by Eubothrium rugosum].

PMID- 14689730
TI  - [Lysozyme content in viscera and blood serum in different fish species of the
      Volga river].

PMID- 14689731
TI  - [Insulin-regulating adenylate cyclase signaling system in cultured fibroblasts of
      the mouse L cell line].

PMID- 14689732
TI  - [Acid-base equilibrium modulates respiratory and digestive behavior in the
      mollusc Lymnaea stagnalis].

PMID- 14689733
TI  - [Reciprocal interaction of the ON- and OFF-system--mechanism of sensitivity of
      visual neurons to the orientation of brightness gradient vectors in cats].

PMID- 14689734
TI  - [Development of laterality of the unconditioned motor reaction in early
      ontogenesis in albino rats].

PMID- 14689735
TI  - [Early effect of neonatal rat sympathectomy on secondary cardiac rhythm].

PMID- 14689736
TI  - [Comparative physiological studies of features for the recognition of two
      dimensional images and three-dimensional objects of different colors and their
      identification by lower and higher monkeys].

PMID- 14689737
TI  - [Localization of NO-ergic elements in mouth, lips and esophagus of the bivalve
      mollusc Crenomytilus grayanus].

PMID- 14689738
TI  - [Effect of interferon-alpha on the hypothalamo-hypophyseal system and the
      pituitary-adrenal system of mice during aging].

PMID- 14689739
TI  - [Evolution of the genetic alphabet and amino acid code].

PMID- 14689740
TI  - Men's health needs attention.

PMID- 14689741
TI  - HIPAA in action.

PMID- 14689742
TI  - Lipid-lowering strategies. Today's therapies and co-therapies can reduce CHD
      risk.

PMID- 14689743
TI  - Patient information. OTC pain relievers: which one is right?

PMID- 14689744
TI  - Breaking down barriers to practice.

PMID- 14689745
TI  - Annual legislative update.

PMID- 14689746
TI  - You must remember this.... An overview of memory loss.

PMID- 14689747
TI  - Hidden dangers. Self-medication by hypertension patients.

PMID- 14689748
TI  - Chronic fatigue syndrome. An overview of current concepts.

PMID- 14689749
TI  - Initial experience with ovarian vein embolization for the treatment of chronic
      pelvic pain syndrome.
AB  - BACKGROUND: Ovarian vein embolization was recently suggested as the preferred
      treatment for chronic pelvic pain syndrome. OBJECTIVE: To evaluate the technical
      feasibility, complications and early clinical and radiographic results of ovarian
      vein embolization in women with pelvic pain syndrome. METHODS: Percutaneous
      transcatheter ovarian vein embolization with coils was performed in six patients
      aged 27-53 years who presented with pelvic pain syndrome. All had lower abdominal
      pain, and pelvic varicosities were found on Doppler ultrasound and retrograde
      ovarian vein venography. Embolization was done unilaterally in three patients (on
      the left side) and bilaterally in three. Mean follow-up by telephone
      questionnaire was 7.3 months. RESULTS: The procedure was technically successful
      in all patients. Two patients reported partial relief of symptoms (33.3%) and
      three had complete relief (50%), for a total of 5 patients (83.3%) with some
      measure of improvement. There were no complications following the procedure.
      CONCLUSIONS: Percutaneous transcatheter ovarian vein embolization seems to be
      safe and feasible for the treatment of pelvic pain syndrome. The procedure is
      performed on an outpatient basis and is well tolerated by patients.

PMID- 14689750
TI  - Methicillin-resistant Staphylococcus aureus nasal colonization in children in
      Jerusalem: community vs. chronic care institutions.
AB  - BACKGROUND: Nasal colonization with methicillin-resistant Staphylococcus aureus
      in the community is being increasingly reported, but there is a general lack of
      data on MRSA colonization in children in chronic care institutions and on
      colonization rates in Israeli children. OBJECTIVES: To define the rate of MRSA
      nasal colonization in a generally healthy pediatric population in Jerusalem, to
      compare it with that of children in chronic care institutions, to define risk
      factors for colonization, and to compare community and hospital-acquired MRSA
      strains. METHODS: Anterior nares culture for the presence of methicillin
      sensitive and methicillin-resistant S. aureus was taken from 831 healthy children
      attending primary pediatric clinics or emergency departments and from 118
      children hospitalized in three chronic care institutions in Jerusalem. RESULTS:
      Of the 831 healthy children, 195 (23.5%) were colonized with S. aureus, as
      compared to 43 of 118 (36.4%) chronically institutionalized children (P < 0.005).
      Five of the 195 S. aureus isolates from healthy children (2.6%) were MRSA, as
      compared to 9 of 43 (21%) from chronically institutionalized children (P <
      0.001). Older age and a family member who is a healthcare worker were associated
      with S. aureus colonization in the population of healthy children, and older age
      was associated with MRSA colonization in the chronically institutionalized
      children. The antibiotic susceptibility pattern was similar for both groups, and
      pulsed field gel electrophoresis of the isolates showed a wide and random
      distribution in both groups. CONCLUSIONS: MRSA colonization in the studied
      pediatric community in Jerusalem was very low, whereas that of patients
      hospitalized in chronic care institutions was significantly higher. In the small
      number of isolates detected, no significant differences were found in antibiotic
      susceptibility or PFGE pattern between hospital-acquired and community-acquired
      strains.

PMID- 14689751
TI  - Door to balloon and door to needle: temporal trends in delays to reperfusion.
AB  - BACKGROUND: Reperfusion practices have changed markedly over the last few years
      with the introduction of primary percutaneous coronary intervention. This
      technique has gained growing popularity in Israel, but little published data are
      available regarding the delays to primary PCI in real life in this country.
      OBJECTIVES: To examine temporal trends in time to reperfusion achieved in a large
      tertiary center over 6 years. RESULTS: Between 1997 and 2002, 1,031 patients were
      admitted to our hospital with ST elevation myocardial infarction. Of these, 62%
      underwent thrombolysis and 38% primary PCI. The proportion of patients referred
      for primary PCI increased steadily, from 14% in 1997 to 68% in 2002. Door to
      treatment time among patients referred for thrombolysis or primary PCI was 54 +/-
      42 and 117 +/- 77 minutes, respectively (P < 0.00001). The door to needle time in
      patients given thrombolysis remained virtually unchanged during the study period
      at around 54 minutes. In contrast, the door to balloon time progressively and
      substantially decreased, from 175 +/- 164 minutes in 1997 to 96 +/- 52 minutes in
      2002. CONCLUSIONS: There is a steady increase in the proportion of patients
      referred for primary PCI than for thrombolysis. The door to needle delay in
      patients given thrombolysis substantially exceeds the recommended time. The door
      to balloon time has declined considerably but still slightly exceeds the
      recommended time. Given the inherent delay between initiation of lysis and
      arterial recanalization, it appears from our experience that PCI does not
      substantially delay arterial reperfusion as compared to thrombolysis. Efforts
      should continue to minimize delays to reperfusion therapy.

PMID- 14689752
TI  - Near-drowning in the Dead Sea: a retrospective observational analysis of 69
      patients.
AB  - BACKGROUND: The Dead Sea in Israel has a very high mineral content. Near-drowning
      in the Dead Sea is expected to result in severe electrolyte abnormalities and
      respiratory failure. Previous limited studies reported a high mortality rate.
      OBJECTIVE: To evaluate the clinical and biochemical manifestations and disease
      outcome of near-drowning in the Dead Sea. METHODS: Data were abstracted from the
      archives of Soroka University Medical Center. The cohort comprised 69 patients
      who nearly drowned in the Dead Sea. RESULTS: The median age of the patients was
      68 years (range 21-84). There were two major manifestations of near-drowning in
      the Dead Sea: electrolyte imbalance and acute lung injury. Serum calcium,
      magnesium and phosphorus (but not sodium, potassium and chloride) were abnormal
      in most patients. Median serum electrolyte levels (and range) on admission were
      10.9 mg/dl (9-24) for calcium, 4.3 mg/dl (1-30) for magnesium, and 4.1 mg/dl (2
      9) for phosphorus. These levels quickly normalized with forced diuresis within 24
      hours. Acute lung injury--namely, hypoxic bilateral pneumonitis--occurred in 29
      patients. Mechanical ventilation was required in 11 patients. Sixty-five patients
      recovered fully, while the remaining 4 had minor sequelae. CONCLUSIONS: Near
      drowning in the Dead Sea is a syndrome of severe electrolyte abnormalities and
      lung injury. Early treatment with forced diuresis and supportive care results in
      prompt recovery.

PMID- 14689753
TI  - Compliance of osteoporotic patients with different treatment regimens.
AB  - BACKGROUND: The treatment of osteoporosis among postmenopausal women represents a
      major public health challenge since long-term therapy is needed to prevent
      fractures and chronic disability. OBJECTIVES: To assess compliance with
      osteoporosis drug therapy among Israeli postmenopausal women treated with either
      a bisphosphonate (alendronate) or a selective estrogen receptor modulator
      (raloxifene); to identify factors affecting compliance among these patients; and
      to compare adherence to the treatment in these two groups. METHODS: Our study
      included 178 consecutive patients aged 67.41 +/- 8.52 years who were treated for
      osteoporosis with alendronate or raloxifene in the Metabolic Bone Diseases Unit.
      All the patients received supplementation with calcium carbonate 1,500 mg and 600
      IU vitamin D daily. Compliance was assessed at a clinic visit 6 months after
      starting therapy. RESULTS: The dropout rate was 23% (41 patients): 20 patients
      (31%) in the raloxifene group and 21 (18%) in the alendronate group (P = 0.0041).
      The main reasons for dropout were side effects and/or noncompliance, 16 and 24
      patients (39% and 58.53%) respectively. The most frequent side effect was
      abdominal pain in 9 patients (42.8%) who discontinued alendronate use. The
      reasons for non-compliance were a fear of side effects and high drug price in 6
      (30%) and 4 (20%) patients respectively in the raloxifene group, and
      inconvenience caused by medication use in 3 patients (14.3%) in the alendronate
      group. Logistic regression analysis of factors that may influence compliance
      included age, previous fractures, family history of osteoporosis, bone density T
      score less than -2.5, and presence and number of concomitant diseases. Age was
      the only statistically significant parameter in this model: 67.8 +/- 8.8 in non
      compliant versus 64.11 +/- 7.4 in compliant patients (P = 0.029). CONCLUSION: At
      least 20% of the patients discontinued chronic treatment for osteoporosis during
      the initial 6 months of therapy. The main reasons were gastrointestinal side
      effects in the alendronate group and fear of side effects and high drug price in
      the raloxifene group. Older age was the only statistically significant factor
      influencing compliance.

PMID- 14689754
TI  - Gene therapy for human immunodeficiency virus infection in the humanized SCID
      mouse model.
AB  - BACKGROUND: The humanized SCID mouse model is an attractive tool for testing gene
      therapy to combat human immunodeficiency virus infection in vivo. OBJECTIVES: To
      devise a more specific gene therapy directed against HIV, replacing the formerly
      used interferon with either soluble CD4 molecule immunoadhesin (sCD4-IgG) and/or
      anti-gp41 monoclonal antibody (2F5), or HIV-negative transdominants genes (Tat,
      Rev). METHODS: Human monocytoid cell line (U937) was transfected with IFN alpha,
      beta or gamma genes. 3T3 murine fibroblastic cell line was transfected with sCD4
      IgG or 2F5, or both genes, and a human T4 cell line (CEM) was grafted to SCID
      mice. Negative transdominant genes (Tat, Rev or both) were also transduced in CEM
      T cell line. Animals were then challenged with HIV-1, Viral load was followed.
      RESULTS: IFN alpha or beta were potent anti-HIV, reducing viral load in vivo and
      inhibiting reverse transcriptase activity in human-removed cells from animals.
      sCD4-IgG immunoadhesin and gp41 monoclonal antibody resulted in a dramatic
      reduction of HIV-1 cellular and plasmatic viral load in humanized SCID mice. The
      simultaneous introduction of negative Tat and Rev genes resulted in a synergistic
      inhibition of HIV-1 replication in vivo. CONCLUSIONS: Despite the marked
      reduction of HIV-1 propagation by IFN genes or by negative Tat and Rev
      transdominants, the gene therapy using soluble CD4 immunoadhesin or anti-gp41 was
      a more efficient preventive treatment against HIV infection.

PMID- 14689755
TI  - Hereditary partial transcobalamin II deficiency with neurologic, mental and
      hematologic abnormalities in children and adults.
AB  - BACKGROUND: Transcobalamin II is a serum transport protein for vitamin B12. Small
      variations in TC-II affinity were recently linked to a high homocysteine level
      and increased frequency of neural tube defects. Complete absence of TC-II or
      total functional abnormality causes tissue vitamin B12 deficiency resulting in a
      severe disease with megaloblastic anemia and immunologic and intestinal
      abnormalities in the first months of life. This condition was described in
      hereditary autosomal-recessive form. Low serum TC-II without any symptoms or
      clinical significance was noted in relatives of affected homozygotes. OBJECTIVES:
      To study 23 members of a four-generation family with hereditary vitamin B12
      deficiency and neurologic disorders. METHODS: Thorough neurologic, hematologic
      and family studies were supplemented by transcobalamin studies in 20 family
      members. RESULTS: Partial TC-II deficiency was found in 19 subjects. Apo TC-II
      (free TC-II unbound to vitamin B12) and total unsaturated B12 binding capacity
      were low in all tested individuals but one, and holo TC-II (TC-II bound by
      vitamin B12) was low in all family members. The presentation of the disease was
      chronic rather than acute. Early signs in children and young adults were
      dyslexia, decreased IQ, vertigo, plantar clonus and personality disorders.
      Interestingly, affected children and young adults had normal or slightly
      decreased serum vitamin B12 levels but were not anemic. Low serum B12 levels were
      measured in early adulthood. In mid-late adulthood megaloblastic anemia and
      subacute combined degeneration of the spinal cord were diagnosed. Treatment with
      B12 injections resulted in a significant improvement. The pedigree is compatible
      with an autosomal-dominant transmission. This family study suggests a genetic
      heterogeneity of TC-II deficiency. CONCLUSIONS: We report the first family with a
      hereditary transmitted condition of low serum TC-II (partial TC-II deficiency)
      associated with neurologic and mental manifestations in childhood. Partial TC-II
      deficiency may decrease the amount of stored cobalamin, resulting in increased
      susceptibility to impaired intestinal delivery of cobalamin and predisposing to
      clinically expressed megaloblastic anemia at a later age. Partial TC-II
      deficiency should be suspected in families with megaloblastic anemia and in
      individuals with neurologic and mental disturbances--despite normal serum vitamin
      B12 levels. Low serum UBBC and apo TC-II should confirm the diagnosis. Early
      vitamin B12 therapy may prevent irreversible neurologic damage.

PMID- 14689756
TI  - New aspects in placental drug transfer.
AB  - The human placenta is the interface between the mother and fetus in the uterus.
      Until recently it was generally believed that the uterus provides a protective
      environment for the fetus. It is now accepted that any chemical substance,
      including any therapeutic agent, administered to a mother is able to permeate
      across the placental barrier. Unfortunately, the placental transfer of substances
      and their distribution in the placenta is not well established. Understanding the
      structure of placental transporters and their function may serve as the ideal
      tool for drug development and the cure of mother and fetus during pregnancy.

PMID- 14689757
TI  - Children born small for gestational age: growth patterns, growth hormone
      treatment and long-term sequelae.

PMID- 14689758
TI  - Gene therapy--where do we go?

PMID- 14689759
TI  - Fibromyalgia: a distinct entity or a biopsychosocial syndrome?

PMID- 14689760
TI  - Fibromyalgia: a distinct entity?

PMID- 14689761
TI  - Fibromyalgia: a biopsychosocial syndrome.

PMID- 14689762
TI  - Laparoscopic-endoscopic assisted treatment of acute bleeding from gastric fundus.

PMID- 14689763
TI  - D-lactic acidosis in a patient after subtotal colectomy.

PMID- 14689764
TI  - Primary genital herpes simplex infection associated with Jewish ritual
      circumcision.

PMID- 14689765
TI  - Lactobezoar and necrotizing enterocolitis in a preterm infant.

PMID- 14689766
TI  - Presentation of Crohn's disease as metastatic cutaneous non-caseating
      granulomatous lesions.

PMID- 14689767
TI  - Traumatic rupture of the diaphragm: CT diagnosis.

PMID- 14689768
TI  - Hypertension control in the family practice.

PMID- 14689769
TI  - Issues of medication administration and control in Iowa schools.
AB  - Who is responsible for medication administration at school? To answer this
      question, a descriptive, self-administered survey was mailed to a random sample
      of 850 school principals in Iowa. The eight-page, 57-item, anonymous survey was
      mailed first class, and a follow-up reminder post card was mailed two weeks
      later. Descriptive analyses were conducted, with type of respondent (principal
      versus school nurse), grade level, and size of school examined to explore
      differences. A 46.6% response rate was obtained; 97% of respondents indicated
      their schools had written guidelines for medication administration. Principals
      (41%) and school nurses (34%) reported that they have the ultimate legal
      responsibility for medication administration. Policies for medication
      administration on field trips were available in schools of 73.6% of respondents.
      High schools were more likely to allow self-medication than other grade levels.
      "Missed dose" was the most common medication error. The main reasons contributing
      to medication administration errors included poor communication among school,
      family, and healthcare providers, and the increased number of students on
      medication. It remains unclear who holds ultimate responsibility for medication
      administration in schools. Written policies typically exist for medication
      administration at school, but not field trips. Communicating medication changes
      to schools, and ensuring medications are available at school, likely can reduce
      medication administration errors.

PMID- 14689770
TI  - Impact of the life skills training curriculum on middle school students tobacco
      use in Marion County, Indiana, 1997-2000.
AB  - Evaluation of school-based tobacco prevention and control programs have yielded
      mixed results. This study assessed the impact of the Life Skills Training
      curriculum on Marion County, Ind., middle school students' knowledge, attitudes,
      and ability to make good lifestyle decisions. From 1997 to 2000, students in
      grades six to eight in the study schools received the Life Skills Training
      curriculum. Survey data (n = 1,598) were used to compare tobacco use behavior,
      attitudes, and knowledge of those exposed with those not exposed to the program.
      Of the students surveyed, 12.5% were currently smoking. There were significantly
      fewer current smokers, and more students exposed to the program indicated they
      intended to stay smoke-free. Fewer of those participating in the program "hung
      out" with smokers and more said they could easily refuse a cigarette if offered
      one. Students completing the Life Skills Training curriculum were more
      knowledgeable about the health effects of smoking. Program effects were different
      for male and female students as well as for White and Black students.

PMID- 14689771
TI  - Teacher perceptions and practices regarding school bullying prevention.
AB  - This study examined a national random sample of teachers regarding their
      perceptions and practices concerning school bullying prevention activities. A
      total of 359 of 700 (52.4%) teachers responded. Most (86.3%) teachers had serious
      talks with both the bully and victim. Less than one-third set aside classroom
      time to discuss bullying (31.7%) or involved students in creating classroom rules
      against bullying (31.2%). Most perceived no barriers to implementing these
      activities. Teachers perceived post-bullying activities as the most effective
      means of reducing bullying problems, followed by improved student supervision,
      and by environmental bullying prevention activities. The findings suggest that
      preprofessional and continuing education are needed to improve teacher knowledge
      about effective classroom-based bullying prevention activities.

PMID- 14689772
TI  - Using counterfactual exercises to enhance decision-making in sexual health.

PMID- 14689773
TI  - The role of vision screening and classroom illumination in the vision health of
      Korean school children.

PMID- 14689774
TI  - [Forensic medical assessment of the skull bone fractures owing to blow impacts
      depending on anatomical characteristics and a nature of a trauma-causing
      objects].
AB  - Fractures in bones of the skull base (BSB) are preconditioned by the contact zone
      of interaction between the two below surfaces, i.e. the trace-forming one
      (object) and the trace-receiving one (bone). On the basis of their independent
      research, the authors suggest a set of criteria for the expert evaluation of
      fractures in BSB for the purpose of specifying the properties of the trauma
      causing object, which is made with due regard for the anatomic specific features
      of the trauma zone.

PMID- 14689775
TI  - [Peculiarities of destruction in the facial area of the skull].
AB  - Injuries observed in the facial skull area (FSA) in trauma made by hard blunt
      objects are registered within the forensic medical examinations of cadavers by
      far more rare than they are actually encountered in life. At the same time, a
      statement made to the effect that it was FSA that was affected in injuries of the
      cerebral skull area (CSA) is of an important forensic medical value. According to
      our research, the "strength beams" present in FSA and CSA are ovals and semi
      ovals positioned above one another in 3 layers (top, medium and low ones). The
      anterior sections of all layers of FSA "strength beams" and of adjoining CSA
      regions, i.e. the squama of frontal bone (low one third of it) as well as
      anterior and middle cranial fossas, are a single deformative strength system.
      Specific features of each impact-zone region affect greatly a character of
      injuries in FSA at traumas in the medium facial third. Bones in the anterior and
      middle cranial fossas are damaged, apart from cranial injuries, in certain
      variations of impacts to FSA.

PMID- 14689776
TI  - [Forensic medical assessment of hemorrhages in hyaline cartilages of the larynx].
AB  - The diagnostic value of hemorrhages to hyaline cartilages of the larynx (CL),
      which is a sign of a trauma in the neck, were investigated. The application of
      term "hemorrhage" in respect to foci of reddish (brownish) coloring of the CL
      tissue was shown to be not always justifiable. Thus, genuine hemorrhages to the
      CL tissue are not altogether possible in children and teenagers owing to the
      original avascularity of their hyaline cartilage tissue; as for women, they are
      possible only in the dorsal CL sections. The reddish coloring results often from
      the imbibition of the CL tissue by hemoglobin at the places of contact of the
      cartilage surface with blood. Such false "hemorrhages" can occur not only in
      trauma but also in nonviolent death and also as artifacts of sectional
      examinations. It was established experimentally that 10 to 12 minutes are
      sufficient for postmortal hemorrhage to set on. The differential diagnosis should
      be made with due respect to the anatomic-and-physiological peculiarities of the
      dead and by applying the hyaline method.

PMID- 14689777
TI  - [Diagnostics of the AB group of AB0(H) system in saliva traces].
AB  - On the basis of the mixed agglutination reaction of the saliva spots, obtained
      from persons with groups A, B, and AB (extractors) as well as mixtures of saliva
      obtained from the above subjects in various combinations, were experimentally
      studied. It was shown to be possible to diagnose the AB group both in the "pure"
      saliva traces and as an admixture of the AB group saliva to the groups A and B
      saliva obtained by using the anti-A and anti-B hetero-immune gemagglutinating
      sera. Our results confirm the previously published opinion on that antigens A and
      B of the ABse group saliva are positioned in the cis-acting mode, i.e. they are
      located on one molecule of surface structure of the epithelial (buccal) cell.

PMID- 14689778
TI  - [Advanced technique for the preparation of bone and tooth tissue for molecular
      genetic expert tests].
AB  - Laboratory schemes related with the procedure of purifying the osseous and dental
      samples by applying the dental drilling machine, dental technical carborundum
      shapes, fogging discs and hard-alloy dental drills were made use of to improve
      the quality and effectiveness of the mentioned schemes used prior to molecular
      and-genetic expertise tests.

PMID- 14689779
TI  - [Diagnostics of the skeletal massiveness and human somatotype using hand bones].
AB  - The skeleton massiveness (SM) and the somatotype of human constitution were
      determined on the basis of osteometry of bones of carpal and metacarpal bones
      (MB) and of phalanxes. Seventy male and 13 female skeletons from the collection
      of the chair for anthropology, Moscow State University, were investigated.
      Described are the results of examinations of 8 carpal bones made according to 3
      signs (length, width, and height), and of 5 metacarpal bones made according to 4
      signs (length, base and head width, and base height); investigation findings of
      finger phalanxes (in full) are also presented. Methods of current
      multidimensional statistics were used within the case study, i.e. related with
      the key components--for SM specification and the discriminative analysis--for
      constitution specification. The SM determination accuracy according to type A was
      40%, according to type B--80%, according to type C--37.5% and according to type D
      -52.9%. The classification accuracy of constitutions by carpal bones was 50.0%,
      by MB--46.4%, and by MB plus finger phalanxes--48.1%. It is pointed out that it
      was for the first time that the elaborated quantitative criteria of osteometry of
      hand bones could be used in the expertise practice for the purpose of personality
      identification by osseous remains.

PMID- 14689780
TI  - [Variants of the signs of death from acute alcohol poisoning stipulated by
      different features of thanatogenesis].
AB  - Two variants of thanatogenesis were formulated in cases of death of acute alcohol
      intoxication; according to the above variants, different combinations of macro-
      and micro signs as well as of biochemical indices of carbohydrates content in the
      hepatic tissues and blood are revealed during cadaver examinations. The
      diagnostic value of the mentioned signs demands that the thanatogenesis specific
      features must be taken into account in each separate case.

PMID- 14689781
TI  - [Forensic medical specificity of death in atypical sexual behavior:
      asphyxiophilia, autoerotism].
AB  - The diagnosis of death of autoerotic asphyxia has not been virtually stated by
      Russian forensic medical expert. All such cases were interpreted as mechanical
      asphyxia entailing suicide, and "accidental" or "fatal" death. The authors
      observed, during the recent 5 years, 10 lethal cases in different-type autoerotic
      practice. Strangulation asphyxia was the death cause in 7 cases. Compression
      asphyxia, inhaling of glue vapor and electric shock caused death, each in one
      case. Death of asphyxia seizes to be exceptional; it is rather a regular
      phenomenon in the present-day life, which needs a proper research from 2
      standpoints--etiopathogenesis, and forensic medical diagnosis.

PMID- 14689782
TI  - [Gas chromatography in quantitative analysis of hydrocyanic acid and its salts in
      cadaveric blood].
AB  - A direct gas chromatography method was designed for the quantitative
      determination of cyanides (prussic acid) in cadaveric blood. Its sensitivity is
      0.05 mg/ml. The routine volatile products, including substances, which emerge due
      to putrefaction of organic matters, do not affect the accuracy and
      reproducibility of the method; the exception is H-propanol that was used as the
      internal standard. The method was used in legal chemical expertise related with
      acute cyanide poisoning (suicide) as well as with poisoning of products of
      combustion of nonmetals (foam-rubber). The absolute error does not exceed 10%
      with a mean quadratic deviation of 0.0029-0.0033 mg.

PMID- 14689783
TI  - [Detection of metals in human tissues by spectrum analysis].
AB  - Potentialities of spectrography experts were demonstrated to be helpful to the
      employees of patient-care facilities (expertise and research institutions) in
      solving a variety of burning issues by joint effort. Tissue samplings, hairs and
      daily urine were comparatively analyzed, by the example of using the low-friction
      hip arthroplasty by comochrome friction Protasu-21WF, for the content of
      microelements (ME) belonging to the hip endoprosthesis. We found that MEs (Co,
      Cr, Mo) are mostly discharged during the first year of endoprosthesis
      utilization, after which, a regular reduction of concentrations was noted. No
      exceeding norms were registered in any cases, which denotes a minimal wear of the
      friction pair.

PMID- 14689785
TI  - [Professor M.E.Stiks--founder of forensic medicine teaching in Tartu (former
      Derpt) university].

PMID- 14689784
TI  - [Differential diagnosis of acute poisoning with narcotics and ethanol].

PMID- 14689786
TI  - [Grigorii Iosifovich Zaslavskii (on 70th anniversary of the birthday)].

PMID- 14689787
TI  - [The epidemic situation in the Russian Federation and measures for its
      stabilization].

PMID- 14689788
TI  - [Efficacy of BCG vaccination].
AB  - Adults born in 1961-1962 and later were found to have skin vaccination marks by 3
      times more less those born before this period. The high risk of diseases in young
      individuals from the family contact inoculated with BCG vaccine was due to
      massive superinfection. The incidence of tuberculosis in individuals under latent
      tuberculous infection is promoted by no or low-grade BCG vaccination.

PMID- 14689789
TI  - [Connective tissue metabolic parameters in differential diagnosis of infiltrative
      pulmonary tuberculosis and pneumonia in patients with signs of connective tissue
      dysplasia].
AB  - Connective tissue dysplasia is a systemic process that modifies the clinical
      picture and course of an acquired pathology. To search additional criteria for
      differential diagnosis, connective tissue metabolic parameters were studied in
      patients with infiltrative pulmonary tuberculosis and nosocomial pneumonia. A
      significant excess of the parameters of free urinary oxyproline and serum
      glycosaminoglycans was found in patients with infiltrative pulmonary
      tuberculosis.

PMID- 14689790
TI  - [Pleural biopsy in the diagnosis of pleurisy: potentialities and efficiency].
AB  - The results of pleural biopsy were analyzed in 293 patients with exudative
      pleurisy, among whom a group of free pleurisy included 88 cases, encapsulated
      pleurisy and pleural obliteration were observed in 156 and 11 patients,
      respectively. Thoracoscopy with visual pinching pleural biopsy was performed in
      59 patients puncture pleural biopsy was made in 234 patients. There is evidence
      for that thoracoscopic pleural biopsy had a significant advantage in pleurisy in
      the phase of organization. An original procedure that has allowed indications for
      thoracoscopic pleural biopsy to be expanded by covering patients with pleurisy in
      the phase of organization is presented.

PMID- 14689791
TI  - [Lung tissue destructive lesions caused by nontuberculous mycobacteria].
AB  - Forty-two patients with pulmonary mycobacteriosis were clinically characterized.
      In most patients, mycobacteriosis developed in the presence of residual changes
      in the lungs after cured tuberculosis. The torpid onset of mycobacteriosis with a
      gradual augmentation of symptoms of intoxication was observed. All the examinees
      were found to have destructive lung tissue changes that were characterized by the
      presence of caverns with a significantly transformed lung pattern.

PMID- 14689792
TI  - [Drug correction of myocardial ischemia in patients with chronic obstructive
      bronchitis].
AB  - To compare the impact of therapy with dialtiazem and enapril on myocardial
      ischemia, this randomized study included 25 patients with chronic obstructive
      bronchitis and myocardial ischemia. A comparative assessment of the results of
      therapy showed a uniform time course of changes in the parameters of Holter
      monitoring and bicycle ergometry (BEM). In a group of patients receiving
      dialthizem, there were reduces in the number of episodes of painful and silent
      ischemia by 66.6 and 72.2%, respectively; the duration of myocardial ischemia and
      the value of the maximum ST depression decreased by 47.4%. In patients receiving
      enalapril, the episodes of painful and silent ischemia became fewer by 55.9 and
      63.6%, respectively; the duration of ischemia and the value of the maximum ST
      depression decreased by 46 and 43%, respectively.

PMID- 14689793
TI  - [Assessment of the use of a multicomponent drug in the treatment of new cases of
      pulmonary tuberculosis].
AB  - The multicomponent drug Mairin-P that contains isoniazid, 60 mg, rifampicin, 120
      mg, pyrazinamide, 300 mg, and ethambutol hydrochloride, 225 mg, has been
      pharmacokinetically and clinically studied. There was no significant difference
      in the pharmacokinetic parameters of rifampicin as a component of Mairin-P and in
      combination with antitubercuous agents as free dosage forms. Treatment of first
      detected patients with pulmonary tuberculosis who isolate drug-sensitive
      Mycobacterium tuberculosis with Mairin-P is as effective as conventional
      treatment regimens with antituberculous drugs. Adverse reactions, including non
      correctable one, due to the use of Mairin-P occur less frequently than to that of
      antituberculous drugs.

PMID- 14689794
TI  - [Efficiency of perstarium in the treatment of patients with chronic obstructive
      bronchitis and pulmonary hypertension].
AB  - Thirty-two patients with chronic obstructive bronchitis (COB) aged 38 to 52 years
      (mean 40.5 +/- 3.8 years) who had clinical and functional parameters of NYHA
      functional class (FC) IV (WHO, 1998) pulmonary hypertension (PH). Hemodynamic
      parameters were recorded by M- and B-mode and Doppler echocardiography. The
      gaseous composition of blood was studied by the Astrup micromethod; the
      rheological properties of venous blood were explored by an AKP-2 rotational
      viscometer. According to their therapy, the examinees were divided into 2 groups.
      Group 1 included 18 patients given prestarium (Servier, France) in a dose of 2-4
      mg/day. Group 2 (a control group) comprised 14 patients receiving the basal
      therapy provided by the medical and economical standards of therapy for COB. The
      studies have indicated that the inclusion of prestarium into the combined
      treatment of COB patients with FC IV PH promotes a significant improvement of the
      clinical status of patients, causes a reduction in the size of the right atrium
      (by 16.2%; p < 0.05) and the right ventricle (by 12.4%; p < 0.001), a 12.0%-fold
      increase in left ventricular ejection fraction. The drug produced no negative
      effect on ERF and blood gaseous composition and rheological properties.
      Therefore, a course and long-term use of prestarium in the combined therapy of
      COB patients with FC IV PH leads to clinical improvement, to correction of basic
      cardiohemodynamic parameters, and exerts a remodeling effect on the right and
      left ventricles, and improves life quality in patients.

PMID- 14689795
TI  - [Functional activity of alveolar macrophages in exacerbation of pulmonary
      tuberculosis].
AB  - The authors estimated the cellular composition of bronchoalveolar lavage fluid,
      the functional activity of alveolar macrophages from the recovery of tetrazolium
      nitroblue (TNB test) in 39 patients with an exacerbation of secondary forms of
      pulmonary tuberculosis before and after prodigiosane stimulation, made a
      correlation analysis in order to elucidate the correlations between the
      parameters of a TNB test and the count of macrophages and neutrophils. On an
      exacerbation of tuberculosis, the activity of a population of alveolar
      macrophages did not increase, but in its infiltrative form, it even decreased as
      compared with the normal values. After prodiogiosane stimulation, the in vitro
      activity of alveolar macrophages increased by almost 60% in infiltrative
      tuberculosis and by 100% in fibrocavernous tuberculosis; there was no substantial
      rise in the activity in tuberculoma. The poor protective functions of alveolar
      macrophages were compensated by the enhanced inflow of alveolar macrophages and
      neutrophils into the airway lumens, as suggested by the correlation between their
      activity and count.

PMID- 14689796
TI  - [Serodiagnostic monitoring of leprosy].

PMID- 14689797
TI  - [Molecular genetics of tuberculosis].

PMID- 14689798
TI  - [Clinical and morphological diagnosis of chronic inflammatory lung diseases].

PMID- 14689799
TI  - Continuing professional development. Evidence-based radiology problems
      transcatheter embolization of rectal laceration: December 2003--November 2004.

PMID- 14689800
TI  - Primary amyloidosis of the breast presenting as nonpalpable microcalcifications:
      case report.

PMID- 14689801
TI  - Ultrasonography or computed tomography for diagnosis in hemodynamically stable
      patients with recent blunt abdominal trauma? Critically appraised topic.

PMID- 14689802
TI  - Computed tomographic features of intraperitoneal fat-containing lesions:
      pictorial essay.
AB  - Abdominal CT, which is a common imaging modality performed for a variety of
      clinical indications, provides an important tool in the diagnosis and evaluation
      of various lesions with fatty components affecting the peritoneal cavity and its
      contents.

PMID- 14689803
TI  - Manually respiratory-triggered single-shot fast spin-echo: a non-breath-hold T2
      weighted method for liver lesion detection.
AB  - OBJECTIVES: To determine whether manual respiratory triggering of a T2-weighted
      single-shot fast spin-echo sequence (M-SSFSE) improves detection and
      characterization of liver lesions compared with conventional breath-held single
      shot fast spin-echo (C-SSFSE) technique. METHODS: M-SSFSE is performed by
      manually triggering a series of single-slice acquisitions through the liver at
      end of expiration. There were 171 hepatic lesions in 49 patients. Images were
      randomized and reviewed by 3 radiologists. Lesions were characterized as
      hemangiomas, cystic or solid. Dynamic gadolinium-enhanced sequences were used as
      the reference standard. Contrast-to-noise ratios (CNR) were calculated for all
      lesions that measured 1 cm or more. RESULTS: M-SSFSE was more sensitive than C
      SSFSE in the detection of liver lesions (48%-58% v. 37%-46%, p < 0.001). There
      were no significant differences in the specificity of lesion detection between
      the 2 sequences. Artifacts were significantly less severe for M-SSFSE compared
      with C-SSFSE (p = 0.001). The CNR was significantly higher for all liver lesions
      on M-SSFSE compared with C-SSFSE (p < 0.001). CONCLUSION: M-SSFSE significantly
      improved hepatic lesion detection and, in particular, improved characterization
      of solid liver lesions and hemangiomas compared with C-SSFSE imaging.

PMID- 14689804
TI  - Diabetic muscle infarction: case report.

PMID- 14689805
TI  - Subperiosteal aneurysmal bone cysts: 2 case reports.

PMID- 14689806
TI  - Effects of metal implants on whole-body dual-energy x-ray absorptiometry
      measurements of bone mineral content and body composition.
AB  - OBJECTIVE: The purpose of this study was to evaluate the influence of metal
      implants on measurements of bone mineral content and body composition by x-ray
      based dual-photon absorptiometry. METHODS: Four whole-body dual-photon
      absorptiometry scans were performed on 13 participants with metal rods either
      present or absent during the scans. The influence of the amount of metal (50 g,
      100 g and 150 g), the proximity of the metal rod to the x-ray source and the
      reproducibility of any metal-induced effects were evaluated by altering the
      position or the size of the metal rod used, or both. RESULTS: The presence of
      metal rods weighing 100 g or 150 g significantly increased reported total body
      mass and bone mineral content (p < 0.034). Soft-tissue mass was increased when
      the scan included the 100-g rod (p < 0.003). The proximity of the metal to the x
      ray source did not have a significant influence on the body composition changes
      induced by the metal. The effects of the metal rods on body composition variables
      were reproducible. CONCLUSION: The presence of metal rods inflated body
      composition variables measured by dual-photon absorptiometry; however, the
      effects are reproducible during repeat scans of an individual patient. Metal had
      the largest impact on whole-body bone mineral content, causing errors of 1.5%-3%.

PMID- 14689807
TI  - Resident's corner. Answer to case of the month #93.  Exercise-induced
      rhabdomyolysis.

PMID- 14689808
TI  - Resident's corner. Answer to case of the month #94. Accessory soleus muscle.

PMID- 14689809
TI  - Internet and scientific publishing.

PMID- 14689810
TI  - Pharmacoeconomic research.
AB  - Efficacy and safety are crucial considerations in judging drugs, for example,
      whether or not to include them in a local formulary. More and more,
      pharmacoeconomic aspects are becoming of additional importance. How should we
      interpret such pharmacoeconomic studies? To enhance accurate interpretation of
      such studies among our readership, we present the basic concepts of
      pharmacoeconomics in this commentary.

PMID- 14689811
TI  - Drug information in psychiatric hospitals in Flanders: a study of patient
      oriented leaflets.
AB  - OBJECTIVE: This study reviews written information sources that inform patients
      about their drugs used in psychiatric institutions in Flanders. METHODS:
      Pharmacists working in psychiatry were asked to participate. Seven leaflets were
      collected and evaluated using the Flesh readability formula and twelve hospital
      pharmacists scored ten propositions on a Likert scale. Questionnaires were mailed
      to the participants. RESULTS: There was wide variation within the three
      readability parameters: reading ease varied from easy to difficult, personal
      interest from tedious/scientific to very interesting/illustrated magazines and
      the quick reading test varied from formal to very popular. Two brochures were
      tedious and formal. As to the content, only three were significantly considered
      'very interesting for patients' (P < 0.05). Most were found to be clear and not
      too long. Concrete information about administration, dosage and duration of
      therapy appeared to be absent from several leaflets. Adverse effects and possible
      complications were thought to be well rendered in most screened sources.
      According to the respondents, the role of the pharmacist was not sufficiently
      mentioned. CONCLUSION: Only three leaflets appeared to be suitable as a patient
      oriented information tool. Pharmacists in psychiatric institutions can contribute
      to patient counselling by providing high-quality leaflets.

PMID- 14689812
TI  - Investigator barriers and preferences to conduct clinical drug trials in Finland:
      a qualitative study.
AB  - OBJECTIVE: To explore investigator barriers, preferences, and attitudes towards
      conducting clinical trials in Finland. METHOD: In-depth, semi-structured
      interviews with 20 clinicians working in the field of cardiovascular medicine
      were performed. The interviews were audiotaped, transcribed verbatim and analysed
      qualitatively. Twenty clinicians from all (five) university hospitals in Finland
      and from three subgroups: 1) with long experience, 2) with limited experience and
      3) reluctant to carry out clinical trials, were sampled purposefully. MAIN
      OUTCOME MEASURES: Barriers and (de)motivating factors in carrying out clinical
      trials and need for training in Good Clinical Practice (GCP). RESULTS: Overall,
      the investigators had a positive attitude towards conducting clinical trials. The
      major barriers seemed to occur at the beginning of the trial: bureaucracy, lack
      of time and laboriousness. The informants hoped for more specific inhouse rules
      and flexibility in hospitals. The greatest investigator barriers were
      insufficient financial incentives, trial-related reasons and administrative
      affairs/bureaucracy. The smallest barriers were reported in subject recruitment,
      clinical work, documentation, investigational product logistics and communication
      with ethics committees. Financial incentives, a possibility to incorporate a
      personal sub-study or other benefits for personal research and scientific and
      clinical interest in the trial were reported as the most motivating factors.
      Carrying out studies in practice and an opportunity to participate in a trial
      during one's postgraduate specialist education were considered beneficial.
      Training in GCP, mainly in the course of postgraduate education, and a
      certificate or equivalent were generally considered necessary, although a
      voluntary system was preferred. CONCLUSION: The interviews of clinicians provide
      valuable information about the barriers and preferences related to the practical
      implementation of clinical trials. If the trial is scientifically/clinically
      interesting and involves a small administrative burden and sufficient financial
      compensation, investigators are motivated to participate. The barriers and
      preferences should be considered in decision-making, to meet the various needs of
      all parties involved and to produce high-quality GCP-compliant clinical drug
      research. This would ensure the availability of sufficient conditions to carry
      out clinical trials also in the future.

PMID- 14689813
TI  - The Weber-curve pitfall: effects of a forced introduction on reporting rates and
      reported adverse reaction profiles.
AB  - BACKGROUND: In May 1999 Losec MUPS (MUPS) were granted a marketing authorization
      in the Netherlands, followed by the withdrawal of the Losec capsules (capsules)
      in September 1999. Both formulations contain omeprazole as active substance. This
      forced switch resulted in a large number of spontaneous reports of adverse drug
      reactions (ADRs) to the Netherlands Pharmacovigilance Centre Lareb. METHODS: We
      calculated and compared the reporting rate of both formulations and grouped the
      reported adverse reactions into system and organ classes (SOCs) in order to
      analyse possible differences in the type of reported ADRs. RESULTS: Lareb
      received 480 reports on omeprazole formulations between May 1997 and December
      2000. A quarter of the reports concerned a decrease in therapeutic effect. The
      reporting rate on MUPS showed a sharp rise after withdrawal of the capsules, but
      did not differ significantly from the reporting rate on the capsules. A
      comparison of the type of reported ADRs showed differences in six SOCs.
      Elimination of the reports concerning a decreased therapeutic effect reduced the
      number of different SOC reporting rates. Certain gastrointestinal complaints were
      reported more frequently as an ADR of MUPS. CONCLUSION: The forced switch caused
      an increase in reports resembling an early Weber effect rather than a decrease in
      safety of the newer formulation. However, our analysis cannot exclude differences
      in pharmacokinetic, pharmacodynamic or safety characteristics.

PMID- 14689814
TI  - Observational study of potential risk factors of medication administration
      errors.
AB  - OBJECTIVE: Medication administration errors (MAEs) are the second most frequent
      type of medication errors, as has been shown in different studies in the
      literature. The aims of this observational study were to assess the rate and the
      potential clinical significance of MAEs and to determine the associated risk
      factors. DESIGN: In two departments, Geriatric Unit (GU) and Cardiovascular
      Thoracic Surgery Unit (CTSU) of Besancon University Hospital (France), MAEs were
      identified using the undisguised observation technique and classified according
      to the definitions of the American Society of Health-System Pharmacists.
      Injectable administration, lack of nurses's standardized protocol for the
      preparation and administration of drugs, incomplete or illegible prescription and
      nurse's workload were analysed as potential risk factors of MAEs in multivariate
      logistic regression analysis. RESULTS: During a period of 20 days, opportunities
      for error concerning 56 patients and 78 MAEs (58 in CTSU and 26 in GU) were
      observed. The medication administration error rate was 14.9%. Dose errors were
      the most frequent (41%) errors, followed by wrong time (26%) and wrong rate
      errors (1996). No potential fatal errors were observed, 8 (10%) were estimated as
      potentially life-threatening, 20 (26%) potentially significant and 50 (64%)
      potentially minor. Nurse workload and incomplete or illegible prescriptions were
      two independent risk factors of MAEs. CONCLUSION: According to these data, the
      quality of the medication administration process needs to be optimized in
      hospitals in order to minimize the incidence of iatrogenic preventable diseases.

PMID- 14689815
TI  - A qualitative approach to the use of economic data in the selection of medicines
      for hospital formularies: a French survey.
AB  - OBJECTIVE: Qualitative interviews were conducted with pharmacists in hospitals
      and clinics in the Rhone-Alpes region of France to determine the role of economic
      data when selecting medicines for formularies, to identify barriers to the use of
      this information and to study to what degree a healthcare establishment's
      financing system influences the use of this data. METHOD: A stratified sample of
      healthcare establishments with over 100 short-stay beds were included: (1)
      thirteen public and semi-private hospitals financed through annual global budgets
      and (2) six private clinics financed on a fee-for-service basis. Interviews were
      carried out between October 1999 and January 2000, and coded independently by two
      researchers. MAIN OUTCOME MEASURE: A multiple correspondence analysis was
      performed to compare the two groups of healthcare establishments. RESULTS: The
      influence of economic data in the decision-making process is limited, for other
      factors appear to have greater weight: (1) efficacy and safety of medicines (2)
      relations between decision-makers and the pharmaceutical industry and (3) patient
      quality of life. Economic data used was mainly related to medication prices and
      quantities consumed. This data was used in a large number of decisions and seemed
      to have more importance in hospitals than in clinics. Information related to
      resources that could be saved by the inclusion of a new medicine on formularies
      was seldom used and apparently considered less important in hospitals than in
      clinics. Pharmacoeconomic evaluations were very rarely used. Six barriers to the
      use of economic data were raised by the pharmacists, including: lack of time,
      which limits the collection and analysis of such information; insufficient health
      economics training, an obstacle to decision-makers' analytical capacity; and
      closed budgets within hospitals. CONCLUSION: Economic data concerning 'medication
      budgets' appears to have a greater impact in public and semi-private hospitals
      than in private clinics. Obstacles linked to the decision-making context itself
      were particularly highlighted, and it can be concluded that in order to increase
      the use of economic data, it is first necessary to create an environment that is
      more favourable to its application.

PMID- 14689816
TI  - Intravenous drug preparation practices: a survey in a French university hospital.
AB  - OBJECTIVE: To describe current practices for i.v. drug admixture preparation, to
      identify potential improvements for the enhancement of patient safety. DESIGN: A
      survey was conducted in a University hospital in Paris. Nurse practices were
      explored through the evaluation of five i.v. drug delivery systems: reconstituted
      freeze-dried drugs administered by syringe or i.v. bags, reconstituted drugs from
      vials administered by syringe or i.v. bags Ready to Use (RtU). PARTICIPANTS: i.v.
      drug preparation practices were documented by a representative sample of nurses
      in the following departments: intensive care, emergency, abdominal surgery,
      cardiology, infectious diseases, hepatology. MAIN OUTCOME MEASURES: Data were
      collected regarding: existence of written procedures for preparations, sources of
      information, labelling, methods of preparation and calculation of doses, nurse
      satisfaction regarding safety and ease of use of the different i.v. systems.
      RESULTS: A total of 299 questionnaires were completed and 100 nurses from the
      chosen wards were surveyed. The study highlighted a lack of procedure (71-85%)
      and a lack of labelling (37%). CONCLUSION: This survey highlighted areas for
      improvement in the preparation of i.v. drugs. It may contribute to raising
      awareness among nurses and physicians about the risks of medication errors. This
      survey also helped the pharmacy department in supporting the development of
      pharmaceutical procedures, the development of satellite pharmacy, the set up of
      training sessions for i.v. preparation and the switch toward ready to use
      packages when these are available.

PMID- 14689817
TI  - Frequency, nature and determinants of pharmacy compounded medicines in Dutch
      community pharmacies.
AB  - AIMS: To examine the frequency, nature and determinants of pharmacy compounded
      medicines in Dutch community pharmacies. METHODS: A prospective nested case
      control study comparing prescriptions for pharmacy compounded medicines (cases)
      with non-pharmacy compounded medicines (controls) was carried out in 79 Dutch
      community pharmacies. 991 Prescriptions for compounded medicines (cases),
      dispensed by the pharmacy on a predetermined day in a specific period (29 March
      until 11 April 2001), and 993 prescriptions for non-compounded medicines
      (controls) randomly selected on the same day, were studied. The nature and
      frequency of compounded medicines as well as patient, drug and prescriber related
      determinants were assessed. In addition, some organisational characteristics,
      like compounding site and use of protocols, were investigated. Also, the value of
      compounded medicines in terms of the availability of an industrially compounded
      equivalent and patient specific reasons, as perceived by the participating
      pharmacists, was evaluated. RESULTS: The overall frequency of prescriptions for
      pharmacy compounded medicines in relation to the total number of prescriptions
      was 3.4%. This means 12.5 compounded medicines per pharmacy per day on average,
      but there was a large variation between pharmacies. Excluding the products
      purchased from specialised compounding companies (28.4%) and the small part of
      medicines coming from other pharmacies (5.2%), we found an overall frequency of
      2.3% of actual compounding in the pharmacy itself. On average, approximately one
      employee was needed for compounding activities with a large variation between
      pharmacies. More than 13% of the pharmacists stated that they delivered more than
      25% of their compounded medicines to other pharmacies. In 2 pharmacies (2.6%) no
      actual compounding took place. For 58% of the products manufactured in the
      pharmacy itself or coming from other pharmacies a (semi-) standardised protocol
      was used. Compared to non-compounded medicines we found a huge share of
      dermatological dosage forms among compounded medicines (62.1% versus 5.3%). Oral
      solutions and ear-nose-throat (ENT) products were also found relatively often.
      While no ATC class was very pronounced in the control group, the group of
      dermatologicals was prominently present in the case group (57%) followed by CNS
      agents (8.4%). The dermatologist was a very strong determinant of compounded
      medicines compared to GPs (ORadj 12.2 [6.3-23.6]). Patients of 12 years or
      younger received a significantly higher rate of compounded medicines than persons
      older than 12 years of age (ORadj 3.4 [2.5-4.8]). Compounding occurred almost
      twice as often when a medicine was prescribed for the first time compared to a
      repeat prescription (ORadj 1.8 [1.5-2.2]). In about 63% of the cases the
      pharmacist judged that an industrially produced medicine could not substitute for
      the compounded medicine. In about 33% of the compounded products they indicated a
      patient specific reason. In about 10% this reason concerned a strictly defined
      pharmaceutical care issue. CONCLUSIONS: Based upon our research, all Dutch
      community pharmacies compound more than 13,000 medicines per day (2.3% of all
      prescriptions). They consist mainly of dermatological preparations. Younger
      children (< 12 yr) receive a significantly higher rate of compounded medicines
      than other people. At least 1.2 compounded prescriptions per pharmacy per day
      have a specific pharmaceutical care reason according to the pharmacists.

PMID- 14689818
TI  - "Death was a blessing"--should it ever be pharmaceutically hastened? British
      pharmacists' views.
AB  - OBJECTIVES: To investigate the views and experiences of British pharmacists in
      physician-assisted suicide (PAS) and voluntary active euthanasia (VAE) and to
      examine whether differences in views were associated with personal
      characteristics. METHOD: A postal questionnaire was mailed to a random sample of
      500 registered pharmacists, with addresses in England or Wales, stratified
      according to sex and community/hospital working environments. MAIN OUTCOME
      MEASURE: Pharmacists' reports of their views and experiences of PAS and VAE.
      RESULTS: Completed questionnaires were received from 295 respondents (response
      rate: 59%). The majority of respondents (83%) reported that at times, a person
      had the right to choose their own manner of death; 61% and 53% thought that there
      should be changes in the Law to legalise VAE and PAS, respectively. If it were
      legal to do so, 63% stated that they would be willing to dispense medication for
      VAE and 64% for PAS. However, only 45% agreed that the pharmacist should have a
      role in advising the prescriber on the choice and dose of drugs used. Sex, age,
      and years registered as a pharmacist were not found to be significantly
      associated with views on the practices of PAS and VAE. However, pharmacists who
      reported having a religion were significantly less likely to favour such
      practices. On comparing the views of community and hospital pharmacists,
      community pharmacists were significantly less likely than expected to want to be
      informed about the intended purpose of lethal drugs. CONCLUSION: In this survey,
      while over half of British pharmacists did not disagree in principle to the
      legalisation of VAE and/or PAS, they were less supportive of direct involvement
      in such procedures. Religion was a discriminatory factor associated with negative
      views of VAE and PAS. The significant minority of pharmacists not wanting to know
      the purpose of drugs they suspected might be for PAS or VAE is not in accordance
      with professional accountability, reflecting the complex and sometimes
      conflicting legal and moral aspects of such practices when deciding upon a course
      of action.

PMID- 14689819
TI  - The clinical and economic impact of a secondary heart disease prevention clinic
      jointly implemented by a practice nurse and pharmacist.
AB  - BACKGROUND: A primary care practice in the West of Scotland used clinical
      governance funding to develop a heart disease prevention clinic to target
      patients with existing heart disease. The practice nurse enlisted the help of the
      practice pharmacist and the protocol for the clinic was subsequently developed
      with the involvement of both practitioners. OBJECTIVE: The aim of this project
      was to identify and offer health screening and appropriate disease modifying
      treatment to patients of a primary care (or general medical) practice suffering
      from cardiovascular heart disease in a clinic run jointly by a practice nurse and
      pharmacist. METHOD: Patients identified by the practice pharmacist were offered a
      full health screen. Their clinical parameters were assessed and appropriate
      disease modifying drug therapy and lifestyle advice was offered in a review
      clinic with the practice nurse and pharmacist. RESULTS: The practice pharmacist
      identified over 212 patients over a 30-month period. A majority demonstrated
      hypertension (91%) and angina (89%), while over half (57%) had suffered a heart
      attack. Statin therapy was modified in a large number of patients (47%) and the
      number of patients with satisfactory total cholesterol levels has increased from
      30% to 57% (P < 0.001). Aspirin and beta-blocker therapy has been initiated in a
      significant number of patients (53% and 26% respectively). Twelve patients (6%)
      stopped smoking; however, many 42% continued to smoke. The general medical
      doctors (GPs) who demonstrated a change in their own practice readily accepted
      changes to therapy recommended by the practice nurse and pharmacist. The practice
      pharmacist offset the additional cost of drug spend on statin therapy by making
      savings in other therapeutic areas. CONCLUSION: A secondary heart disease clinic
      can benefit patients by optimising drug and lifestyle therapy. While the
      inclusion of a pharmacist confers clinical and economic benefits.

PMID- 14689820
TI  - Impact of pharmacist recommendations on the cost of drug therapy in ICU patients
      at a Malaysian hospital.
AB  - OBJECTIVES: To analyse clinical pharmacists interventions in the ICU of the
      Penang General Hospital (Penang, Malaysia) and to assess the pharmaco-economic
      impact of these interventions. METHODS: A clinical pharmacist reviewed drug
      prescriptions during one month. Drug-related problems were documented on a
      prepared from including a suggestion for a change in prescribing. Such
      recommendations were submitted to the nursing/medical staff. Acceptance of the
      recommendation was entirely at the discretion of the medical staff. All
      recommendations were analysed with respect to potential pharmaco-economic impact:
      cost savings, cost avoidance or cost addition. RESULTS: The ICU pharmacist made
      57 recommendations, of which the medical staff rejected only 5%. The majority of
      detected drug-related problems referred to unnecessary drug therapy (37%).
      Recommendations resulted in net cost savings of RM 15,227 (USD 4,007). This
      corresponded with RM 634 per patient intervened by the pharmacist. CONCLUSION:
      Pharmacists interventions in the ICU of a Malaysian hospital resulted in
      significant cost savings in terms of drug expenses and can therefore be suggested
      as a routine practice in our hospital.

PMID- 14689821
TI  - [Subclinical hypothyroidism with emphasis on the cardiovascular system].
AB  - Subclinical hypothyroidism is comparatively frequent disorder with incidence
      between 3 to 7% in the general population; in females over 60 it can exceed 10%.
      There is no unequivocal view on the clinical significance of the syndrome;
      however, it may correspond with increased risk of atherosclerosis and its
      complications. Especially in elderly women, screening for subclinical
      hypothyroidism is recommended with possible hormone replacement according to
      given criteria. Decision about the therapy of subclinical hypothyroidism should
      be done together with cardiologist, psychiatrist or neurologist in order to
      correct possible clinical impacts and prevent further manifestations.

PMID- 14689822
TI  - [Amyopathic dermatomyositis].
AB  - Dermatomyositis represents a progressive autoimmune disease of the connective
      tissue with SLE-like dermatitis, with inflammatory myopathy and muscular
      weakness. It is an infrequent and serious disease affecting not only the skin and
      striated muscle. Cases without skin affection are classified as polymyositis.
      Beside autoimmune mechanisms, aetiology includes also genetic, environmental and
      paraneoplastic factors. Clinical skin symptoms as well as histopathological
      findings include Gottron's papulae, heliotropic periorbital erythrema, which,
      together with palpebral oedema, brings about the weepy look of patients. None of
      these signs is pathognomic and beside the cutaneous symptoms the diagnosis
      requires 3 out of 4 other diagnostic criteria for the muscle symptoms. Cutaneous
      symptoms can precede myositis with various time intervals; such situation is
      sometimes classified as Amyopathic dermatomyositis (ADM), dermatitis sine
      myositis or skin dermatomyositis. A case of an ADM patient and the analysis of
      problematic including the strategy of therapy are presented.

PMID- 14689823
TI  - [Correlation of results of flow cytometry and morphologic findings in the
      diagnosis of malignant B-cell lymphoma].
AB  - BACKGROUND: Immunophenotyping of malignant lymphomas becomes necessary for the
      correct classification, for the design of therapy and for prognosis projection
      (WHO). Although the spectrum of classic immunohistochemical (IHC) examinations in
      paraffin embedded or frozen sections has recently considerably extended, IHC
      should preferably be combined with flow cytometry. The main advantage of flow
      cytometry is a synchronous application of two or more antibodies marked with
      various fluorochromes in one sample. The method is limited by utilizing native
      material only. METHODS AND RESULTS: The flow cytometry combined with histological
      and IHC investigations were used in diagnosis of primary non-Hodgkin's lymphomas
      of B-cell origin (B-NHL) and for bone marrow staging or restaging. We studied 90
      patients with confirmed or suspected B-NHL and we found a good correlation in 89%
      of samples of primary lymphomas and in 85% of bone marrow samples when IHC and
      flow cytometry results were compared. The overall efficacy of the flow cytometry
      determination in lymphoma infiltration of the samples was 89%. CONCLUSIONS:
      Immunophenotyping utilizing flow cytometry contributes to diagnosis and
      classification of B-cell lymphomas in the significant proportion of investigated
      patients. In some cases it is even unnecessary to employ IHC examination of
      tissue sections. The method is especially suitable for determination of
      monoclonal populations of B-cells by detection of cell surface markers because it
      is more specific and sensitive than IHC. The immunophenotyping by flow cytometry
      as an auxiliary method and in correlation with morphological findings it can make
      the diagnosis of B-cell lymphomas faster and more specific.

PMID- 14689824
TI  - [Initial experience with magnetic resonance cholangiopancreatography].
AB  - BACKGROUND: Magnetic resonance cholangiopancreaticography (MRCP) is based on
      heavily weighted T2 sequences (ETSE--echo-train spin echo) with suppression of
      fat, giving visualisation of slowly flowing or stagnating fluid. MRCP are short
      sequences in coronary plane with thickness of 8 cm or 4 mm. Retrospective
      analysis of all MRCP examinations performed during last 12 months is presented.
      METHODS AND RESULTS: Eighty-eight examinations were done, of which 67 ones with
      both adequate technical quality and clinical indication were included into the
      study (20 males aged 25-83 years, 47 women aged 19-82 years). Patients were
      divided into 4 groups regarding to the indications (group I.--temporary
      cholestasis, normal abdominal ultrasound, II.--definite cholestasis, III.-
      pathologic findings on pancreas, IV.--other). Vast majority of patients were
      included into group I (35 subjects). In 7 (20%) of them choledocholithiasis
      and/or stenoses (including multiple stenoses in primary sclerotizing
      cholangoitis) were found. MRCP brought diagnostic information in subjects with
      cholestasis (group II.) and answered questions given by clinicians. However, in 1
      of 4 subjects with primary sclerotizing cholangoitis, MRCP did not reveal intra
      hepatic stenoses, which were later visualised by classical ERCP. Only the
      extrahepatic stenoses were diagnosed by MRCP in the latter subject. CONCLUSIONS:
      MRCP should become a standard examination in the diagnostic algorithm in patients
      with cholangiopathies. MRCP has its value not only in subjects with unsuccessful
      or contraindicated ERCP, but also in subjects with temporary cholestasis with
      negative ultrasound finding.

PMID- 14689825
TI  - [Heat shock protein antibodies and other chlamydial antigens in various diseases
      and their occurrence in blood donors].
AB  - BACKGROUND: The chlamydial infections are very frequently considered in the
      causal connection with some diseases e.g. atherosclerosis or chronic joint
      infections. The evidence of the antibodies against the heat shock protein of
      chlamydial origin is not the usual part of practical serological diagnostics. The
      aim of this study is an attempt to identify antibodies against the heat shock
      protein and other antigens of chlamydiae in the sera of two groups of patients
      and in the sera of blood donors. METHODS AND RESULTS: The sera of patients
      suffering from unstable angina pectoris (NAP = 69), sera of patients waiting for
      the application of endoprothesis due to coxarthrosis (EKK = 49), and sera of 100
      blood donors have been examined for antibodies against the heat shock protein,
      against the major outer membrane protein (MOMP) of C. pneumoniae, and against the
      chlamydial genus specific lipolysaccharides. The antibodies against the cHSP60 in
      the sera of patients suffering from NAP have been identified in 41 cases (59.4%),
      in orthopaedic patients in 21 cases (42.9%) and in 23 of the blood donors (23%).
      The difference of the antibody-occurrence in the sera of patients is
      significantly higher than in case of blood donors. The antibodies against the
      MOMP of C. pneumoniae prevailed in all sera of the persons examined. Their
      occurrence in the IgG class had a high statistical frequency. The genus specific
      positive reaction occurred more frequently also in the sera of the probands that
      reacted positively against the cHSP60 than in those negatively reacting.
      According to our results, the significance of C. pneumoniae in the genesis of the
      antibodies against of cHSP60 can be concluded. CONCLUSIONS: The proof of the anti
      cHSP60 antibody and of the species-specific chlamydial antibodies may be a useful
      contribution to the exact diagnosis of the disease with possible chlamydial
      participation. The C. pneumoniae infection was probably of the main importance
      for the origin of the anti-cHSP60 antibody in examined persons.

PMID- 14689826
TI  - [Detection of Helicobacter pylori in the saliva of patients with recurrent
      aphthous stomatitis].
AB  - BACKGROUND: Helicobacter pylori participates significantly on the pathogeny of
      chronic gastritis, duodenal and gastric ulcer, carcinoma and lymphoma of the
      stomach. There are some more diseases requiring attention--for example
      cardiovascular, dermatologic, and autoimmune. METHODS AND RESULTS: Helicobacter
      pylori was detected in saliva and faeces of 28 persons by the Premier platinum
      HpSA diagnostic set. Levels of IgA and IgG antibodies were determined by EIA and
      Western Blott methods. Parameters of salivary immunity were investigated as well.
      Levels of IgG, SIgA, IgM, lysozyme and albumin were determined. Recommended
      therapy of Helicobacter infection led to an evident clinical improvement and
      descent of the documented Helicobacter pylori antigen. CONCLUSIONS: Helicobacter
      pylori infection can probably participate in some cases of relapsing aphtous
      stomatitis.

PMID- 14689827
TI  - [Chromosome Y microdeletions in Czech men with severe reproductive disorders].
AB  - BACKGROUND: The Y chromosome microdeletions belong to the frequent genetical
      causes of male infertility. The aim of our study was to introduce reliable
      molecular genetic diagnosis of Y chromosomal microdeletions and to determine the
      prevalence of Y chromosomal microdeletions in Czech males with serious
      reproductive disorders. METHODS AND RESULTS: The Y chromosome microdeletions were
      screened in 198 Czech men with serious reproductive disorders with decreased
      sperm count. The Y chromosome microdeletions were disclosed in 8/198 (4.0%)
      examined males. The AZFc deletion type was revealed in 62.5% (5/8) and the
      combined AZFc + b microdeletion in 37.5% (3/8) of cases. Neither isolated AZFb
      nor AZFa microdeletion were found in any subject of the investigated group.
      CONCLUSIONS: Incidence of individual types of Y chromosomal microdeletions in
      Czech males with serious reproductive disorders was assessed. The standardised
      molecular genetic diagnosis of Y chromosomal microdeletions was introduced into
      the practice.

PMID- 14689828
TI  - [Epidemiology of severe injuries from the viewpoint of the trauma center].
AB  - BACKGROUND: Injuries represent the major cause of mortality in the age group up
      to 45 years. In the Czech Republic, the majority of injuries is caused by traffic
      accidents. According of statistic data incidence of injuries is increasing.
      METHODS AND RESULTS: Traumatological Hospital Brno is Trauma Centre level I for
      two districts (2 mil. people). In 1999, the epidemiological prospective study was
      initiated, monitoring patients with injured at least two body structures and with
      Injury Severity Score higher than 16. After four years, the group includes 880
      patients (75.7% of males). The average age was 39.3 years (14-97 years). The main
      cause of injury was a traffic accident (72%), the second cause was a downfall
      (20%). CONCLUSIONS: The average value of ISS is 27, the mortality decreased
      significantly from 22% in 1999 to 11% in 2002. Occurrence and types of injuries
      in traffic participants are analysed.

PMID- 14689829
TI  - [Comparative pathology of early stress-induced changes in the duodenal mucosa in
      laboratory rats and in humans].
AB  - BACKGROUND: Our presentation comprises results of two studies: The first was an
      experimental investigation of 60 Wistar-strain rats used in a toxicological
      study. The other part analysed stress changes in the duodenal mucosa in the human
      autopsy material. Both humans and rats had been exposed to stress and showed
      similar histological changes. METHODS AND RESULTS: In the rats the same duodenal
      lesions were present both in the test group and the control animals in the
      toxicological study. Lesions consisted of oedema of the duodenal villi and
      erosions in the tips of the villi. We believe that in the experimental group the
      stress was caused by restraining the animals by daily introduction of the gastric
      metallic tube, by taking blood from the retrobulbar plexus, and by anaesthesia.
      CONCLUSIONS: The autopsy study comprised 35 cases displaying congestion and
      macroscopically recognizable multifocal bleeding into the duodenal mucosal folds.
      The microscopic investigation revealed bleeding into the mucosal villi and small
      erosions. In some cases there were cuneiform mucosal infarcts extending into the
      submucosa. In the humans, severe cardiovascular diseases and circulatory
      disturbances represented the main causes of the stress. Local hypoxia and gastric
      juice acidity were involved in the pathogenesis of the duodenal mucosal changes.

PMID- 14689830
TI  - [Hereditary thrombocytopenia. Differential diagnosis of a case].
AB  - Hereditary thrombocytopenias are a heterogeneous group of extremely rare diseases
      characterized by a reduced number of blood platelets and by bleeding tendency of
      variable severity. Some of these diseases are exclusive to platelets, while in
      others the pathology extends to other cell types. Although rare, hereditary
      thrombocytopenias should be considered in the diagnosis. Hereditary
      thrombocytopenias have been classified into three groups depending on platelet
      volume. Hereditary thrombocytopenias with giant platelets form one of these
      groups. About fourteen clinical entities of inherited giant platelet disorders
      have been described. Bernard-Soulier syndrome, grey platelet syndrome and May
      Hegglin anomaly are the most common giant platelet thrombocytopenias. May-Hegglin
      anomaly is condition characterized by the triad of thrombocytopenia, giant
      platelets, and pale-blue inclusions in leukocytes. May-Hegglin anomaly has an
      autosomal-dominant mode of inheritance. We described clinical and laboratory
      features of three adult women from one family with recently diagnosed May-Hegglin
      anomaly. Described cases are probably the first observed cases of May-Hegglin
      anomaly in the Czech lands.

PMID- 14689831
TI  - [Diagnosis of Helicobacter pylori infection in childhood with a novel
      immunoenzyme method (HpStAR) which detects antigens in feces using monoclonal
      antibodies ].
AB  - BACKGROUND: Premier Platinum HpSA EIA is an enzyme immunoassay developed for
      diagnosis of H. pylori infection using polyclonal antibodies against H. pylori in
      human stool. A new H. pylori stool antigen test, based on monoclonal antibodies,
      has been developed. Our aim was to evaluate prospectively the accuracy of the
      novel antigen stool test (DAKO HpStAR) using monoclonal antibodies for detection
      of H. pylori infection in children. METHODS AND RESULTS: Total of 93 children
      undergoing upper gastrointestinal endoscopy were included in the study. Biopsy
      specimens were sampled from the gastric antrum and from the corpus. Patients were
      classified as H. pylori positive if histology and urease test were positive. All
      children provided a stool sample within 3 days after gastroscopy. IgG serology
      against H. pylori was also employed. HpStAR test was performed according to the
      manufacturers protocol. Results were read at 450/630 nm by spectrophotometry (cut
      off point 0.150). Of the 93 children, 26 were H. pylori positive (13.1 +/- 3.2
      yr), and 67 patients were H. pylori negative (12.8 +/- 4.7 yr). Only 2 children
      were misclassified (1 false negative, and 1 false positive). Sensitivity was
      96.1%, specificity 98.5%, the positive and negative predicting values were 96.1%
      and 98.5%, respectively. Serology showed sensitivity 88.5%, specificity 70.2%;
      the positive and negative predicting values were 53.5% and 94% respectively.
      CONCLUSION: HpStAR test based on monoclonal antibodies can be considered an
      accurate, non-invasive, reliable method for the diagnosis of H. pylori infection
      in children.

PMID- 14689832
TI  - [General medicine as an academic discipline].
AB  - The aim of the article is to show emerging changes in the health care, which will
      require some adaptation of curricula of medical faculties. It also considers the
      role of general practice in those changes and it emphasizes the potential of
      general practice for the undergraduate medical education and for the primary care
      research. Three questions are discussed: What can the subject of general practice
      offer to medical faculties? What can the medical faculties do for the general
      practice? At universities, the discipline "General practice" should become,
      similarly to the real health care, the first bridge between books and the live
      human. At higher classes, it should represent a clinical field with its position
      in the health care system, with its definition and characteristics. Similarly to
      other countries, general practice should offer all attributes of a medical branch
      for the full accomplishment of medicals, including their scientific work and
      teaching. It would require further developing of its academic basis. Society will
      be then awarded with higher quality of medical care offered by general
      practitioners.

PMID- 14689833
TI  - [Role of morphology in medical education, clinical practice and research].
AB  - Rapid development of molecular biology, biochemistry, physiology and other
      sciences has diminished the previously dominant role of morphology in the
      theoretical part of medical studies. Morphology, closely related to various
      disciplines, should, however, be included in clinical lectures. Changes in the
      curricula would require concise and well-structured textbooks, based on recent
      clinico-morphological studies, for the theoretical parts of both medical and
      allied health care study programmes. Comprehensive textbooks are still necessary
      for the specific needs of clinicians and researches.

PMID- 14689834
TI  - [Anatomy today differs from that of the last half of the past century].

PMID- 14689835
TI  - [Tempora mutant et nos mutamur in illis (reply to the article by Dr. J. Valenta].

PMID- 14689836
TI  - [Aging and immunity].

PMID- 14689837
TI  - [Current state of understanding of SARS and infection control measures].

PMID- 14689838
TI  - [The ideal aged society--important roles of gerontology].

PMID- 14689839
TI  - [Stress and aging].

PMID- 14689840
TI  - [A new strategy of aging and geriatric epidemiology in Japan].
AB  - Global trends of increases in the aging population will continue in the 21st
      century, and geriatric medicine will be a most important field of medicine.
      Increase in the aging population naturally causes increases in numbers of
      patients with geriatric disease. Geriatric diseases are often chronic, slowly
      progressive, and hard to cure. Medical care expenses for the patients will expand
      dramatically. Therefore, the most important key for future geriatric medicine is
      prevention. For prevention, detailed data on normal aging process are required.
      At the National Institute for Longevity Sciences (NILS), a comprehensive
      longitudinal study of aging, the NILS-Longitudinal Study of Aging (NILS-LSA)
      started in November 1997. The subjects of this study were about 2,300 residents
      aged 40 to 79 years who were stratified random samples selected from the
      neighborhood area of the NILS. They are examined every two years at the NILS-LSA
      Examination Center. The third wave of examinations started in 2002. Examined
      variables were over 1,000, including clinical evaluations, medical examinations,
      anthropometry, body composition, physical functions, physical activities,
      psychological assessments, nutritional analysis and molecular epidemiology.

PMID- 14689841
TI  - [Progress and problems in the research on Alzheimer's disease].

PMID- 14689842
TI  - [Osteoporosis: from pathogenesis to therapy].

PMID- 14689843
TI  - [Toward the effective control of aging via energy metabolism and stress
      response].

PMID- 14689844
TI  - [Rehabilitation for the promotion of functioning: a program based on the goal
      oriented approach].

PMID- 14689845
TI  - [Functional brain imaging in the aged].

PMID- 14689846
TI  - [The assistive device in self-support for the elderly--role of assistive devices
      as independence from the physical and mental restrictions].
AB  - The development of assistive self-support devices was an important strategy for
      improving quality of life in the elderly. After introduction of care insurance,
      independence from the physical and metal restrictions was recommended. In order
      to improve quality of life and independence form restrictions, we have developed
      several assistive devices. A baby-doll mimicking a baby was made add applied to
      the therapeutic program. This doll therapy has been used in several facilities
      for healing elderly, especially dementia patients. To prevent falls, a power
      assisted walker was developed to compensate and support elderly gait. A fall
      detector was used to estimate falling and to develop guidelines for the
      prevention of fall.

PMID- 14689847
TI  - [DNA damage, repair and aging].
AB  - Oxidative DNA damage has been shown to accumulate with age in the nuclear and
      mitochondrial genome and cause cancer. Among DNA lesions produced by reactive
      oxygen species, base lesions and single-strand breaks are most frequently
      produced and cause mutation and cell death. However, these lesions are
      effectively repaired by base excision repair, which is very well conserved from
      bacteria to human. Since many proteins are involved in the repair process,
      understanding of their functions and the effects of repair deficiency will
      provide the relation between DNA damage and aging-related diseases. For this
      purpose we analyzed the proteins involved in the repair of oxidative DNA damage
      and found novel mechanisms protecting mammals against oxidative stresses.

PMID- 14689848
TI  - [Longevity and genes].

PMID- 14689849
TI  - [Up to date of Japanese health care].

PMID- 14689850
TI  - [Strategy for the medical care of the elderly--establishment of net work system
      in the region].

PMID- 14689851
TI  - [Medical association activities and geriatric medicine].

PMID- 14689852
TI  - [To live in the hospital; being made alive in the hospital--consideration about
      the terminal care of the aged patient].

PMID- 14689853
TI  - [Relation of hypertension and glucose tolerance impairment in elderly people to
      the development of arteriosclerosis--investigation using pulse wave velocity].
AB  - Hypertension and diabetes are risk factors for arteriosclerosis and have a
      synergistic effect on the progression of arteriosclerosis. The aim of this study
      was to determine the correlation between complications of hypertension and
      diabetes and arteriosclerosis as assessed by pulse wave velocity (PWV) in elderly
      subjects. The subjects of this study were 186 people aged 60 years or older (mean
      age: 68.8 +/- 5.8 years) who were scheduled to undergo health examinations. PWV,
      systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index
      (BMI), fasting blood sugar (FBS), total cholesterol (TC), triglyceride (TG) and
      HDL cholesterol (HDL) were measured in each subject. The patients were divided
      according to the American Diabetes Association (ADA) diagnostic criteria for
      diabetes based on fasting blood sugar level into the following three groups: a
      normal (NGT) group (FBS < 110 mg/dl), an impaired fasting glucose (IFG) group
      (110 < or = FBS < 126 mg/dl) and a diabetes mellitus (DM) group (FBS > or = 126
      mg/dl or receiving treatment for diabetes). Based on the JNC-VI and WHO/ISH
      diagnostic criteria, subjects who had a SBP of 140 mmHg or higher or a DBP of 90
      mmHg or higher or who had been taking hypotensive drugs were assigned to the
      hypertension (HT) group, and the other subjects were assigned to the normotension
      (NT) group. PWV showed significant positive correlations with SBP and FBS (r =
      0.499 and r = 0.300, respectively). The effects of hypertension on PWV were
      significantly higher in subjects with HT than in subjects with NT in all of the
      glucose tolerance groups (all p < 0.01). Moreover, in the subjects with HT, PWV
      started to increase from the IFG stage, and PWV was significantly higher in the
      DM groups than in the NGT group (p < 0.01). In multiple regression analysis using
      PWV as an objective variable, SBP and FBS were selected as significant
      explanatory variables. The results of this study indicate the need for stricter
      management of elderly people with slight glucose tolerance impairment and
      hypertension in order to prevent the occurrence of arteriosclerosis.

PMID- 14689854
TI  - [Effect of pneumonia on clinical course and prognosis after hip fracture].
AB  - The records of 38 elderly patients with hip fracture admitted to our hospital
      between January and December 2002 were retrospectively reviewed to determine the
      incidence and outcomes of medical complications. The mean age was 84.5 +/- 6.83
      years old, 32 women and 6 men. 27 patients (71%) suffered from dementia. Of the
      38 patients, 33 (86.8%) had one and more underlying diseases: hypertension 29,
      cerebrovascular episode 7, congestive heart failure 5, diabetes mellitus 4,
      gastric ulcer or chronic gastritis 3, ischemic heart disease 4, depression 2.
      Three patients had a past history of hip fracture. Fourteen patients (37%)
      developed medical complications after hip fracture, most frequently pneumonia
      (64%). Other complications were dizziness, nausea, congestive heart failure,
      choledocholithiasis, and GI tract bleeding. Eight patients who suffered pneumonia
      cancelled elective surgery. Severity of pneumonia was mild in 2, moderate in 5,
      and severe in 2. Both cases with severe pneumonia died in hospital. Patients with
      pneumonia (pneumonia group) were significantly older and had more severe dementia
      than patients without pneumonia (non-pneumonia group). Although there were no
      significant differences in physical ability between the two groups before
      admission, physical ability on discharge was lower in the pneumonia group. The
      pneumonia group had a significantly longer mean hospital stay than the non
      pneumonia group. Our results suggest that the prevention of pneumonia is
      necessary to improve the outcome of hip fracture.

PMID- 14689855
TI  - [Age-related changes of lipid peroxidation in food-restricted rats based on
      determination of phosphatidylcholine hydroperoxide in the plasma, liver and
      kidney by high-performance liquid chromatography with fluorometric post-column
      detection].
AB  - Age-related changes of phosphatidylcholine hydroperoxide (PCOOH) were
      investigated in male Dawley rats aged 3 to 18 months, either fed ad libitum or
      dietary restricted (maintained on 60% of ad libitum food intake). Although there
      are many reports dealing with age-related changes of lipid peroxidation, they
      were exclusively results obtained by the non-specific thiobarbituric acid method.
      In this study, we measured PCOOH as an index of oxidative stress by a specific
      assay method using high-performance liquid chromatography with fluorometric post
      column detection. The PCOOH levels in ad libitum-fed rat plasma, liver and kidney
      increased with age. Dietary restriction significantly suppressed the age-related
      PCOOH accumulation in the plasma. In dietary restricted rat liver, PCOOH levels
      tended to be suppressed by the restriction. In dietary restricted rat kidney,
      they were not due to until 12 months of age, but the levels at 18-months of age
      were suppressed by the restriction. Life span is mainly influenced by pathologic
      lesions. The increase in PCOOH levels with age can cause biomembrane damage, and
      appears to be involved in the development of lesions. Suppression of PCOOH level
      by dietary restriction appears to suppress the morbid conditions which shorten
      life span.

PMID- 14689856
TI  - [Factors associated with municipality officers' recognition of relief for elderly
      life in each municipalities: the community health care white paper survey].
AB  - To elucidate the present condition about health, medicine and welfare, and to
      evaluate factors associated with relief for elderly life in each community, a
      questionnaire survey was conducted among officers of all the municipalities in
      Japan. We asked officers about their recognition whether older people can live
      feeling relieved or not, and other factors about health, medicine and welfare
      condition in each municipality. Demographic data of each municipality were also
      used as dependent variables. Odds ratios and their 95% confidence intervals for
      the officers' evaluation of relief for life of the elderly were calculated using
      unconditional logistic models. Of the 3.252 municipalities, 3,059 (94%) responded
      to the survey. Of the respondents, 2,957 municipalities (91%) answered questions
      about relief for elderly life. "Receiving satisfactory medical home care
      service", "cooperative function between medicine, health, and welfare sections",
      and "receiving complete welfare service" were associated with their recognition
      about relief for elderly life in both of cities and rural towns. In addition,
      "the rate of elderly households" and "the easiness to maintain nursing staff"
      were associated in the cities. This study indicated that more arrangements are
      needed not only about health and welfare aspects, but also about medical service,
      especially medical home care service systems to support older peoples' life in
      the community.

PMID- 14689857
TI  - [A case of serious aspiration pneumonia associated with multiple cerebral
      infarctions and Alzheimer's disease followed by hospital and home care service
      team].
AB  - A 81-year-old man, who had been diagnosed in multiple cerebral infarction and
      Alzheimer's disease, was followed up in his local clinic since 1997. He had been
      bedridden before admission, but could eat. He was admitted with severe aspiration
      pneumonia in December 1999. Since severe dementia and dysphagia were noted after
      admission, he was examined to find out whether or not he could swallow while the
      treatment of his pneumonia was conducted at the same time. The water swallowing
      test indicated a risk of aspiration, thus, percutaneous endoscopic gastrostomy
      was performed on January 26, 2000 after the completion of the treatment for
      pneumonia. Although the patient's condition was complicated by aspiration
      pneumonia, enteral feeding through the gastric fistula gradually became
      successful, and he was discharged in June 2000. His family physician followed him
      up by visiting at home to examine and observe his general physical condition
      including consciousness, vital signs, skin and respiration, while taking measures
      in cooperation with the local health care visiting nurse. The patient,
      thereafter, was repeatedly admitted and discharged because of exacerbation and
      remission of symptoms, including coughing, sputum and fever, probably caused by
      aspiration pneumonia. When he was admitted in December 2001, which was his sixth
      admission, since there were troubles with the infusion tube and frequent
      gastroesophageal reflux, the gastric fistula management was judged to be a great
      burden on the patient. In January 2002, the gastrostomy tube was removed and the
      patients, whose alimentation was managed using intra-venous hyperalimentation
      (IVH), was discharged. Besides periodic visits by his family physician, a 24-hour
      house visit system was introduced to control his IVH and deal with his family
      members' anxiety. His general condition, thereafter, has not markedly changed.
      The patient has continuously received medical treatment for 14 months after being
      discharged and his condition is stable.

PMID- 14689858
TI  - [Principal features of the present issue of the Journal of Anatomy].

PMID- 14689859
TI  - [Balancing teaching and research in anatomy and medical schools].

PMID- 14689860
TI  - [Does gross anatomy have a future?].

PMID- 14689861
TI  - [Special plans for training young anatomical scientists with teaching ability: is
      it effective to introduce the team system of employment?].

PMID- 14689862
TI  - [Education and research in anatomy in Japan--present and future].

PMID- 14689863
TI  - [Novel approach to respiratory pharmacology--pharmacological basis of cough,
      sputum and airway clearance].
AB  - Disturbance of the normal mucociliary clearance due to hyperproduction of mucus
      and modification of its physicochemical characteristics is a common finding in
      airway diseases. Drugs that affect airway secretion have been developed and used
      to cleanse the respiratory tract for many centuries and in many countries. On the
      basis of the mechanism of their actions, the mucoactive drugs are classified into
      several groups. Some mucoactive drugs have direct effects on the production or
      composition of airway secretions, resulting in increased effectiveness of
      mucociliary clearance. Other mucoactive drugs do not have a specific action on
      mucus, but have beneficial effects on airway structure and function, which lead
      to correction of the pathophysiologic mechanisms that result in abnormal
      secretions. However, since many drugs have overlapping effects, it is difficult
      to classify these drugs into groups based on their major actions. Taken together
      with previous findings on mucoactive drugs, it appears that an antioxidant effect
      is a common property of mucoactive drugs and that it is a crucial action to exert
      their effects against airway diseases. In light of this idea, we must use
      specific experimental models to simulate pharmacologic events in airway
      inflammation. The development of new techniques has made it possible to identify
      and measure the mucus components, measure the rheologic parameters more
      accurately, and evaluate mucociliary clearance precisely in animals and humans.
      Therefore, with modifications of methods, we have investigated airway-cleansing
      drugs from various points of view to reflect actions in inflammatory states for
      more than two decades. Here, I introduce the methods we have used to study many
      of the parameters involved in airway clearance, including cough reflex, and
      describe some of the mucoactive-antitussive drugs that we have studied recently.
      There is an increasing usage of traditional Chinese herbal medicines in clinics
      and hospitals, because they tend to have moderate side effects and sometimes
      remarkable efficacy. To renormalize overall defects in airway disorders, Chinese
      medicines may be adequate, because they are composed of various herbs with weak
      but ubiquitous pharmacologic activities. We have been investigating Bakumondo-to.
      Bakumondo-to has been used for the treatment of bronchitis and pharyngitis
      accompanying severe dry cough. We found that unlike codeine Bakumondo-to had a
      notable antitussive activity against the cough associated with bronchitis and the
      cough increased by angiotensin-converting enzyme inhibitors. Recently, we have
      found that, in alveolar type II cells, Bakumondo-to attenuated
      phosphatidylcholine secretion increased by oxygen radicals from activated PMNLS.
      In addition, we found that Bakumondo-to itself stimulated phosphatidylcholine
      secretion and increased beta-adrenoceptor gene expression in rat alveolar type II
      cells. We studied the mechanism of action and clarified that Bakumondo-to
      increased glucocorticoid-sensitive promotor activity. The effect may contribute
      to its ubiquitous effectiveness in the treatment of airway diseases. Various
      parameters (chemical properties, physical properties, mucus production,
      surfactant phospholipid production, and mucociliary clearance) are considered to
      be important for the dynamics and mobilization of airway secretions.
      Pharmacologic investigation, with appropriate techniques, of the ability of an
      agent to modify these parameters can provide useful information about its
      mechanism of action. However, since these parameters are interconnected, it is
      very complicated to elucidate the precise mechanisms of action of mucoactive
      drugs. This means that the goal of treatment cannot always be achieved by the
      modification of a single parameter, but should, more realistically, be aimed at a
      renormalization of several parameters. On the basis of this idea, glucocorticoids
      are ideal mucoactive drugs because they exert various pharmacologic effects in
      the lung. From a polypharmacologic point of view, a traditional Chinese medicine
      can be classified as a glucocorticoid-like drug because Chinese medicines consist
      of many types of active components that have various pharmacologic effects. As
      one future course of research, we believe that efforts to seek compatible actions
      between glucocorticoids and Oriental medicines may lead to new opportunities for
      development of ideal airway-cleansing drugs with specific actions, i.e.,
      suppression of gene expression.

PMID- 14689864
TI  - [Development of new synthetic methods and their application to synthesis of
      useful compounds].
AB  - Development of novel synthetic methodologies and their application to synthesis
      of natural products are described. The first topic is about an extension of the
      scope of our indole synthesis by radical cyclization of o-alkenylphenyl
      isocyanides. By utilizing this methodology and nitrogenzenesulfonamide chemistry,
      an efficient total synthesis of hexacyclic aspidosperma indole alkaloid,
      aspidophytine, was accomplished. As the second generation indole synthesis, we
      then developed the method by radical cyclization of o-akenylthioanilides.
      Synthetic utility of this method was fully demonstrated by a total synthesis of
      iboga alkaloid, catharanthine. Furthermore, a total synthesis of vinca alkaloid,
      vinblastine through a practical synthesis of vindoline was achieved, in which the
      stereochemistry of the crucial coupling reaction of two indole fragments could be
      completely controlled. In addition to the indole chemistry, exceptionally mild
      transformations of thiol esters to ketones and alkenyl ketones have been
      developed. Examples of application of the protocols for the synthesis of natural
      products are also described.

PMID- 14689865
TI  - [The effects of indomethacin spray on the pain of stomatitis in the patients for
      hematopoietic stem cell transplantation].
AB  - We studied the effects of 0.25% indomethacin (IM) spray as an in-hospital
      preparation on the pain of stomatitis after hematopoietic stem cell
      transplantation in 9 patients with various types of leukemia by measuring the
      change in pain and the decrease in morphine dose. Stomatitis above grade 2
      (painful erythema, edema, or ulcers but can eat or swallow) appeared in all
      patients as white blood cell (WBC) counts declined after transplantation, and
      clockwise hysteresis was observed between WBC counts and the grade of stomatitis.
      When the patients used IM spray for the pain of stomatitis and were judged the
      grade of pain using a face scale of five grades (0-4) before and after the use of
      this spray, the mean grades of pain at the maximal pain during the appearance of
      stomatitis declined from 3.4 to 1.8 (n = 5). Furthermore, the concurrent
      intravenous dose of morphine markedly decreased during IM spray use. There was no
      complaint concerning the taste and convenience of IM spray by patients. The risk
      of systemic adverse effects was considered relatively low based on the small
      amounts of IM applied to the mouth mucosa. In conclusion, it is suggested that IM
      spray is effective for the relief of stomatitis pain in patients who have
      undergone hematopoietic stem cell transplantation and is a useful preparation for
      immediate self-medication upon the appearance of stomatitis pain. We considered
      that the application of IM spray will contribute to the improvement of patient
      quality of life.

PMID- 14689867
TI  - [Calculation of drug information necessity factor of generic drugs].
AB  - The utilization of generic drugs has been promoted, but there is concern about
      the insufficiency of the information provided on generic drugs. To make an
      objective evaluation of the amount of information supplied by generic drug
      manufactures, we tried to quantify the information supply. The information
      described in the package insert and the interview form were used in the
      evaluation. We sent a questionnaire to 1000 randomly selected hospitals
      nationwide to determine the necessity of each information item in medical
      practice, and weighted the score allotted to each item based on replies from 524
      hospitals. We applied these procedures to diclofenac sodium products and found
      that the score for a branded drug was 60.5 points and that for generic drugs
      ranged from 1.6 to 58.3 points. This indicates that there were great variations
      in information supply activities among the manufacturers. The Qua value, which
      was the ratio of the points of a generic drug per unit price in the drug tariff
      to the points of the branded drug, ranged from 0.1 to 2.4. We think that these
      procedures will make it possible to select the appropriate generic drugs in
      medical practice.

PMID- 14689866
TI  - [Does collagenase affect the electrophysiological parameters of nerve trunk?].
AB  - Collegenase is widely used in the process of teasing a nerve in order to perform
      single fiber action potential (SFAP) recordings. In this study, the effects of
      collagenase on nerve conduction parameters were investigated. To accomplish this,
      normal compound action potentials (nCAPs) were recorded from isolated frog
      sciatic nerve at various distances using the suction technique. Then, the same
      nerve was treated with collagenased Ringer's solution (3.5 mg/ml, Sigma Type XI)
      for 90 minutes and action potentials (cCAPs) were recorded again. Numerical
      analysis of these records was performed and the results were compared. Using the
      nCAP and cCAP recordings, the conduction velocity distributions (CVD) of the
      individual nerve trunks were determined by a method that we have previously
      described. Statistical results indicated significant differences (p < 0.05)
      between the nCAP and cCAP CVD data. From these findings it is concluded that,
      when used for teasing the nerve fibers, collagenase may affect the nerve trunk
      conduction parameters. Specifically, a significant amount of decrease has been
      observed in conduction velocities of myelinated fibers having diameters smaller
      than 8 microns.

PMID- 14689868
TI  - [Analysis of the oral hypoglycemic agent, glibenclamide, in a health food].
AB  - Glibenclamide, a sulfonylurea derivative (SU) antidiabetic agent was detected in
      a health food by three different methods: TLC, HPLC, and liquid chromatography
      mass spectrometry (LC-MS). For analysis of SU antidiabetics, the sample was
      extracted with acetone as a sample solution. TLC analysis of the sample solution
      showed a specific spot that had the same characteristics as those of
      glibenclamide standard solution. HPLC analysis monitored using a photo-diode
      array detector showed that the sample solution had a peak with a unique UV
      spectrum, with coincided with that of standard glibenclamide. In sample solution,
      LC-MS analysis in positive and negative modes indicated that the (M + H)+ and (M 
      H)- ions occurred at m/z 494 and m/z 492, respectively. These results indicate
      that the monoisotopic mass is 493, coincident with that of glibenclamide.
      Quantitative HPLC analysis showed that the glibenclamide content in the health
      food was 0.78 mg/capsule (1.55 mg/g of sample contents). Because the initial
      dosage of glibenclamide for diabetics is 1.25-2.5 mg per day, this health food
      has sufficient medicinal effect and also has the potential to cause adverse
      effects.

PMID- 14689869
TI  - [Long-term follow up of re-induction with a new synthetic retinoid, Am-80, for
      relapse of acute promyelocytic leukemia previously treated with all-trans
      retinoic acid: results of 7 cases from a single institute].
AB  - Seven patients experiencing first (n = 5) or second (n = 2) relapse of acute
      promyelocytic leukemia (APL) were treated with a new synthetic retinoid, Am-80.
      All 7 patients were previously treated with all-trans retinoic acid (ATRA). Am-80
      was orally administered at a dose of 6 mg/m2 daily. Chemotherapy was combined in
      3 patients because of leukocytosis. All 7 patients achieved a complete remission
      (CR) during periods ranging from 36-56 days (median 52 days). Adverse effects
      such as hyperlipidemia and skin lesions, were tolerable. After achieving CR, 3
      patients underwent allogeneic bone marrow transplantation and 4 patients received
      only consolidation chemotherapy. In 2 of 3 patients who received allogeneic
      transplantation, relapse free survival has lasted for 9.7 and 28.3 months.
      Furthermore, in 2 of 4 patients who received only chemotherapy, relapse free
      survival has lasted for 84.7 and 90.1 months. Am-80 is an active agent for APL
      patients who have relapsed from ATRA-induced remission.

PMID- 14689870
TI  - ['Reverse' variant of follicular lymphoma with monoclonality of the
      immunoglobulin heavy chain and T cell receptor gamma chain genes].
AB  - We report an unusual case of the 'reverse' variant of follicular lymphoma in
      which the nodules had central parts that stained dark and cuffs that stained
      pale. Because diagnosis was difficult relying only on formalin-fixed
      histopathology, we examined the cell surface markers and karyotype. The patient,
      a 65-year-old man, presented with multiple lymphadenopathy, low-grade fever,
      night sweats, anorexia, dry cough and sense of chest oppression. Cell surface
      marker analysis showed that pathologic lymphocytes were positive for CD 10, CD
      19, CD 20, HLA-DR, IgM/IgD and kappa, and t (14; 18) (q 32; q 21) was detected by
      karyotypic analysis. The 'reverse' variant of follicular lymphoma, clinical stage
      IVB was diagnosed the rearrangement band was detected with PCR-based clonality
      analysis in not only the immunoglobulin heavy chain gene but also the T cell
      receptor gamma chain gene, thus confirming monoclonal proliferation of both B
      cells and T cells.

PMID- 14689871
TI  - [Successful T-cell-replete peripheral blood stem cell transplantation from an HLA
      2 loci mismatched mother to her son with refractory anemia in myelodysplastic
      syndrome].
AB  - A 15-year-old male with refractory anemia in myelodysplastic syndrome underwent
      peripheral blood stem cell transplantation from his two-loci-mismatched
      haploidentical mother. The conditioning regimen was comprised of
      cyclophosphamide, busulfan, and fludarabine. Non-T-cell-depleted peripheral blood
      stem cells were infused with graft-versus-host disease (GVHD) prophylaxis
      consisting of tacrolimus and short-course methotrexate. Engraftment was confirmed
      on day 18, and complete chimera on day 29. Although the patient developed grade
      II acute GVHD following the transplantation, it responded rapidly to steroid
      administration. The subsequent course was uneventful, and he remains well in
      complete remission in 26 months after transplant. This successful experience
      suggests that maternal hematopoietic stem cell transplant for children, in
      specific immune tolerance based on the presence of microchimerism and
      compatibility of minor histocompatibility antigens between mother and child, may
      have given rise to the favorable preventing effect against severe GVHD.

PMID- 14689872
TI  - [Sustained remission of MDS overt leukemia associated with abrupt discontinuation
      of immunosuppression following relapse after the second course of allogeneic
      hematopoietic stem cell transplantation].
AB  - The case of a 32-year-old female with relapsed myelodysplastic syndrome (MDS)
      after second course of allogeneic transplantation is described. The peripheral
      blood stem cell transplantation was performed as early as 3 months after the
      initial bone marrow transplantation because of rejection and relapse; however,
      the patient again relapsed 2 months later. Immediate discontinuation of
      cyclosporine resulted in the progression of pancytopenia and the development of
      high fever, liver dysfunction and skin eruption. The patient was then treated
      with dexamethasone, which successfully stabilized these symptoms. After these
      clinical events, a dramatic hematological response was obtained; the blast rate
      was reduced from 10.6 to 0% in bone marrow aspiration, and pancytopenia was
      restored to normal levels. Moreover, fluorescence in situ hybridization analyses
      with X and Y chromosome-specific probes revealed that hematopoietic precursor
      cells were predominantly of donor origin. The patient subsequently received donor
      lymphocyte infusion (DLI) from the original donor. Currently, 2 years after DLI,
      the patient continues to be in remission.

PMID- 14689873
TI  - [Successful recovery of an acute myelogenous leukemia patient from a coma
      possibly due to leukoencephalopathy].
AB  - A-36-year-old male diagnosed with acute myelogenous leukemia (AML, M2) failed to
      achieve a complete remission after having undergone two courses of induction
      chemotherapy (idarubicin hydrochloride + cytarabine, high-dose cytarabine), and
      moreover, his cerebrospinal fluid (CSF) then revealed abnormal blasts. Dosages of
      30 mg of methotrexate, 80 mg of cytarabine, and 40 mg of prednisolone acetate
      were given via lumbar puncture, and following this treatment, the leukemic cells
      were no longer detectable in his CSF. As a prophylaxis for meningeal leukemia
      relapse, he continued to receive intrathecal chemotherapy (methotrexate,
      prednisolone acetate) twice a week, and later he underwent reinduction therapy
      (second high-dose cytarabine). He displayed mental disorientation on the thirty
      seventh day after he had been given a high-dose of cytarabine (araC). Up to the
      thirty-seventh day, he had also been given a total of 135 mg of intrathecal
      methotrexate. On the thirty-ninth day he fell into a coma, and his brain computed
      tomography (CT) demonstrated low density areas in the white matter, in addition
      to edema. These findings were compatible with leukoencephalopathy. With the
      administration of glycerin and methylprednisolone, his condition, however, began
      to reverse, and by the fifty-third day his brain edema had subsided and his
      mental condition had improved. On the ninetieth day he began to walk without
      assistance, and after the third course of re-induction chemotherapy, he achieved
      complete remission. He is currently doing well.

PMID- 14689874
TI  - [Successful radiotherapy for the thoracic cord infiltration of adult T-cell
      leukemia/lymphoma].
AB  - A-51-year-old woman with a sixteen-year history of mixed connective tissue
      disease was admitted to the Kitasato University Hospital because of hypogastric
      pain in September 1999. Colonofiberscopy and computed tomography in the abdomen
      demonstrated thickening of the intestinal wall with a hemorrhagic ulcer in the
      terminal ileum. The histopathologic findings of the lesion revealed diffuse
      infiltration of atypical T-lymphocytes. The titers of anti-HTLV-I antibody and
      serum soluble IL-2 receptor were elevated. The diagnosis of adult T-cell
      leukemia/lymphoma (ATLL) infiltrating the terminal ileum was made. Combination
      chemotherapy including VEPA-M was undertaken, and resulted in a partial response.
      ATLL became refractory about June 2000. Flaccid paralysis, dysesthesia in the
      left lower limb and bladder-bowel disturbance emerged in a few days, July 2000.
      T2-weighed MRCT images demonstrated that a lesion with a high intensity signal
      was present in the spinal cord around Th 7. Flower-like cells were detected in
      the cerebrospinal fluid. Infiltration of ATLL into the thoracic cord was
      diagnosed. Administration of intrathecal methotrexate and prednisolone, systemic
      dexamethasone and local irradiation of 30 Gy improved the paralysis and the
      abnormal MRCT findings. Rehabilitation restored the patient's ability to walk.

PMID- 14689875
TI  - [Acute lymphoblastic leukemia in childhood treated with non-T-cell depleted bone
      marrow transplantation from an HLA 2 loci (HLA-A and-DRB1)-mismatched mother
      after early graft failure of cord blood transplantation].
AB  - An 11-year-old boy with acute lymphoblastic leukemia received unrelated cord
      blood transplantation at the second remission. Because of early graft failure, he
      was given a second non-T-cell depleted bone marrow transplant from his HLA 2 loci
      (HLA-A and -DRB1)-mismatched mother 36 days after the first transplantation. Feto
      maternal microchimerism was verified before transplantation. The second
      transplantation was performed with fludarabine/melphalan as a conditioning
      regimen, and tacrolimus/short-course methotrexate as graft-versus-host disease
      (GVHD) prophylaxis. Engraftment was prompt with a recovery of neutrophils (> 0.5
      x 10(9)/1) by day +10, reticulocytes (> 1%) by day +17 and platelets (> 50 x
      10(9)/l) by day +18. Mild regimen-related toxicities (grade I gastrointestinal,
      grade II hepatic) were observed and acute GVHD was grade I (skin: stage 2). No
      severe complication was noted. At 6 months post-transplantation, he had no
      chronic GVHD or leukemia relapse. This experience indicates the future
      feasibility of a back-up non-T-cell depleted transplantation from HLA 2 loci
      mismatched and feto-maternal microchimerism-positive mothers in cases with
      primary graft failure.

PMID- 14689877
TI  - [Philadelphia chromosome-positive acute lymphoblastic leukemia showing normal
      karyotype at presentation].
AB  - 21-year-old male was diagnosed as having acute lymphoblastic leukemia (ALL) in
      March 2001. Standard G-banding analysis revealed normal karyotype. He achieved
      complete remission after the first course of induction therapy and underwent
      allogeneic PBSCT in August 2001. However, leukemic cells appeared in the
      peripheral blood demonstrating complex chromosomal abnormalities with
      Philadelphia chromosome (Ph1) and expressing minor BCR/ABL transcripts. We thus
      retrospectively examined the bone marrow sample at presentation with both
      interphase FISH and RT-PCR methods. Surprisingly, almost all leukemic blasts at
      presentation turned out to possess the minor type of BCR/ABL fusion gene. In
      spite of the second allogeneic PBSCT, the patient died of pneumonia and graft
      versus-host disease in the liver in September 2002. This case is rare in that
      cytogenetic analysis failed to detect Ph1 due to leukemic cells dormancy. The
      application of both FISH and RT-PCR studies would appear to be essential to avoid
      overlooking Ph1-positive ALL.

PMID- 14689876
TI  - [Primary malignant lymphoma arising from the nipple and areolar area of the
      breast].
AB  - A 56-year-old woman noticed soreness and swelling in the right nipple. Two weeks
      later, she noticed a mass in the outer lower region of the right areolar area,
      which was excised and the pathology of which was consistent with diffuse large B
      cell lymphoma (DLBCL). She was admitted when the right nipple mass was noted to
      be increasing, and was diagnosed as having stage I lymphoma. Her nipple mass was
      excised, and the pathology was consistent with DLBCL. CHOP therapy was
      administered three times and she was judged as having complete remission.
      Malignant lymphoma accounts for 0.15-0.17% of primary breast malignancies. Though
      the nipple and areolar area seem to be a rare primary site, this should be
      recognized as a sentinel zone for malignant lymphoma.

PMID- 14689878
TI  - [Acute myelogenous leukemia complicated with severe tumor lysis syndrome after a
      single day of idarubicin/cytarabine chemotherapy].
AB  - We describe a patient with acute myelogenous leukemia (AML) who was complicated
      with severe tumor lysis syndrome (TLS) after a single day of chemotherapy; a
      previously unreported occurrence. A 48-year-old man was admitted because of fever
      and bleeding tendency, and was diagnosed as having AML: M1. His white blood cell
      count (WBC) was 66, 300/microliter with 96% myeloblasts. Chemotherapy with
      idarubicin and cytarabine was started. On the second day of the therapy, he
      developed acute renal failure (ARF) and deterioration of disseminated
      intravascular coagulation (DIC) with a marked reduction in his WBC
      (8500/microliter). Immediately after a diagnosis of tumor lysis syndrome (TLS),
      the following chemotherapy was discontinued. Hemodiafiltration and hemofiltration
      were initiated to treat the ARF, concomitant with anticoagulant and
      antifibrinolysis therapy for the DIC. Chemotherapy with daunorubicin and
      cytarabine was resumed on the 12th day, recognizing a regrowth of leukemic cells.
      Thereafter a complete remission was achieved without recurrence of the TLS.

PMID- 14689879
TI  - [Hypereosinophilic syndrome developing after prednisolone therapy for autoimmune
      hemolytic anemia].
AB  - A 26-year-old woman was diagnosed as having autoimmune hemolytic anemia in
      September 2002. Her eosinophil count was already high (2,190/microliter) at that
      time. She received prednisolone therapy with a good response and was released
      from the treatment in April 2003. Eosinophil numbers were within the normal range
      under the prednisolone administration. However, they began to increase after its
      completion. No underlying causes for the eosinophilia were evident. When the
      eosinophil count reached 5,474/microliter, the patient developed massive pleural
      effusion as well as palpebral swelling and myalgia, leading to a diagnosis of
      hypereosinophilic syndrome. Re-administration of prednisolone resulted in the
      disappearance of these symptoms and eosinophilia. Her eosinophils seemed to have
      reactivated after cessation of the prednisolone therapy and infiltrated into her
      organs.

PMID- 14689880
TI  - [Treatment of gastric cancer: current state and future prospect].

PMID- 14689881
TI  - Distance of the femorotibial joint gap can be controlled in the modified ligament
      dependent cut procedure during total knee arthroplasty.
AB  - During total knee arthroplasty in fifty consecutive cases, the distal femur and
      proximal tibia were initially cut. After posterior cruciate ligament excision,
      the femorotibial joint was expanded by a Tensor/balancer device with 30 inch
      pounds of torque (in.lbs) both in extension and flexion, and ligament balancing
      was obtained in full extension. Then the knee was flexed at 90 degrees, and the
      femoral rotational axis was decided so that the axis was parallel to the tibial
      cut surface and the joint gap was the same between extension and flexion. The
      relationship between the distance of the joint gap expanded by a Tensor/balancer
      device with 30 in.lbs and the size of the bearing insert was assessed. The
      results showed that a 24 or 25-mm joint gap expanded by a Tensor/balancer device
      in full extension was optimal for a 10-mm bearing insert. Therefore, if the
      resection level of the tibia is set 24 or 25 mm from the femoral cut surface, a
      10-mm bearing insert can be used. In 49 cases, the size of the femoral component
      was one size (4 mm) larger than that predicted based on the bony structure shown
      in the radiographs of the knee. With this procedure, ligament balancing and
      optimal joint gap both in extension and flexion can be obtained based on the
      predicted bearing insert in the knee.

PMID- 14689882
TI  - [Mass screening for prostate cancer is the best approach to early diagnosis and
      treatment of prostate cancer].
AB  - To achieve the goal of early detection, diagnosis and treatment of prostate
      cancer in China, mass screening for prostate cancer using serum prostate specific
      antigen (PSA) has been performed in men over 50 years. We compared this result
      with the clinical cases. It proved that only through the mass screening can we
      really find the early stage prostate cancer and be given the chance of curing the
      cancer. We also investigated the current treatment situation and problems and
      figured out the further direction on the prostate cancer research.

PMID- 14689883
TI  - [Effects of daidzein on sperm quality, testis gain and testosterone in mice].
AB  - OBJECTIVE: To evaluate the effects of daidzein on sperm quality of male mice.
      METHODS: Three different doses of daidzein were supplemented to pubertal male
      mice for 21 days(5 mg/kg, 100 mg/kg, 1,000 mg/kg ration). The viability of sperm
      was determined by eosin-Y, the acrosome was observed by Wright-Giemsa staining,
      and the testosterone was measured by radioimmunoassay. RESULTS: Daidzein at the
      dose of 5 mg/kg ration significantly increased serum testosterone levels (P <
      0.01), prompted testis gain (P < 0.05), and improved spermatozoa quality.
      Daidzein at dose of 1,000 mg/kg ration could inhibit the secretion of serum
      testosterone (P < 0.01), without significant variation in spermatozoa quality.
      Daidzein at dose of 100 mg/kg ration did not significantly affect sperm quality
      and other index. CONCLUSIONS: Daidzein can affect sperm quality and in dosage
      dependant ways.

PMID- 14689884
TI  - [Effects of testosterone on GDNF mRNA expression in rat ventral prostate].
AB  - OBJECTIVE: To investigate the effects of testosterone on GDNF(glial cell-derived
      neurotrophic factor) expression in rat ventral prostate. METHODS: Twenty-four
      male Sprague-Dawley rats were randomized into 3 groups, group A(n = 8, sham
      operation, uncastrated controls), group B (n = 8, castrated), group C (n = 8,
      castrated and given testosterone undecanoate (TU) 50 mg/kg by intramuscular
      injection). Ventral prostate tissues removed from adult male rats at 3 days after
      operation were analyzed for the expression of GDNF mRNA by semiquantitative RT
      PCR assay. RESULTS: The ventral prostate tissues shrank remarkably in the
      castrated rats, and prostatic hyperplasia accurred in those that had received
      both castration and testosterone undecanoate. GDNF mRNA expressed in the normal
      rats ventral prostates, and the prostatic expression of GDNF mRNA decreased
      significantly at 3 days after castration(P < 0.05), but increased significantly
      (P < 0.05) in those that had received both castration and TU. CONCLUSIONS: The
      gene expression of glial cell-derived neurotrophic factor in the ventral prostate
      of rats is dependent on testosterone, and GDNF is involved in the growth of rat
      ventral prostate.

PMID- 14689885
TI  - [Effects of catheter depth and infused semen volume on the pregnancy of
      intrauterine insemination].
AB  - OBJECTIVE: To evaluate the effects of catheter depth and infused semen volume on
      the pregnancy rate of intrauterine insemination(IUI) with the husband's semen.
      METHODS: According to different catheterizing distances from the fundus and
      infused semen volumes, 330 patients undergoing intrauterine insemination were
      randomly divided into 6 groups: A, 1 cm/0.5 ml; B, 1 cm/0.3 ml; C, 2 cm/0.5 ml;
      D, 2 cm/0.3 ml; E, 3 cm/0.5 ml and F, 3 cm/0.3 ml. The pregnancy rate was
      investigated in each group. RESULTS: The pregnancy rates from group A to group E
      were 9.09% (5/55), 12.73% (7/55), 10.91% (6/55), 29.09% (16/55), 9.09% (5/55) and
      12.73% (7/55), respectively. It was significantly higher in group D than in
      groups A, B, C, E and F(P < 0.05). CONCLUSIONS: Catheterizing distance of 2 cm
      from the fundus with infused semen volume of 0.3 ml can significantly improve
      pregnancy rate in patients undergoing IUI with the husband's semen.

PMID- 14689886
TI  - [A long-term follow-up study of deep penile vein resection patients].
AB  - OBJECTIVE: To study the five-year postoperative effect of the ligation and
      resection of the deep penile vein for the patient of erectile dysfunction (ED)
      caused by penile venous leakage. METHODS: Sixteen ED patients received deep
      penile vein ligation and resection. Observations of the penile erection had been
      recorded for 5 years after surgery. RESULTS: Eight cases demonstrated erectile
      hypofunction after 18 months postoperatively and total ED after 21-30 months of
      which 6 were improved by chemotherapy, and 2 showed no improvement. Seven cases
      remained normal and 1 case get out of touch at the 24th month postoperatively.
      CONCLUSIONS: The ligation and resection of the deep penile vein can be considered
      as an easy and effective method to treat patients of ED caused by penile venous
      leakage.

PMID- 14689887
TI  - [Clinical investigation of the treatment of children urethral calculi with
      pneumatic lithotripsy under ureteroscopy].
AB  - OBJECTIVE: To evaluate the therapeutic effects of pneumatic lithotripsy on
      children urethral calculi. METHODS: Twenty-two cases of the male children with
      urethral calculi were treated with pneumatic lithotripsy under ureteroscopy.
      RESULTS: All the patients were treated successfully in a single procedure. The
      time of lithotripsy was (5.5 +/- 2.2) minutes, and no serious complication such
      as obvious hematuria, infection and urethral stricture occurred. CONCLUSIONS: It
      is suggested that pneumatic lithotripsy under ureteroscopy is an effective and
      simple way for the treatment of urethral calculi in children.

PMID- 14689888
TI  - [Treatment of chronic bacterial prostatitis by perfusion with double-balloon and
      triple-channel catheter: a control study].
AB  - OBJECTIVE: To investigate the efficacy of the double-balloon and triple-channel
      catheter (DBTC) in the treatment of chronic bacterial prostatitis (CBP). METHODS:
      One hundred and three CBP patients were randomly assigned to three different
      groups and received three different therapies, respectively: 1. 61 cases by
      transurethral perfusion and drainage with antibiotics with DBTC catheter; 2. 29
      cases by intravenous antibiotics, and 3. 13 cases by transurethral irrigation
      with 0.9% saline. The lecithin, white blood cells (WBC) in expressed prostatic
      secretion (EPS) and Meares-Stamey's test fractionary urine culture pre- and post
      therapies were compared. RESULTS: The improvement rates of clinical symptoms and
      lecithin corpuscles were 81.9% and 68.9%, respectively. And the decline rate of
      WBC and bacteriological efficacy rate were 75.4% and 91.8%, respectively. There
      was a significant statistical difference between the DBTC group and the
      intravenous group in the lecithin, WBC and bacterial culture (P < 0.05, < 0.01
      and < 0.01, respectively), and so was there between the saline group and the
      intravenous group in the decline of WBC(chi 2 = 5.6, P < 0.05), but with no
      difference in lecithin and bacterial culture. Among 61 patients treated with
      DBTC, 3 developed mild allergic reaction in urethra. CONCLUSIONS: Transurethral
      DBTC has a better clinical efficacy than traditional intravenous treatment for
      CBP. DBTC perfusion combined with other hypurgia holds obvious advantages of
      being safe, effective, easy and repeatable in the treatment of CBP.

PMID- 14689889
TI  - [Combined use of TUVP and TURP for treating BPH (report of 179 cases)].
AB  - OBJECTIVE: To investigate a new operation method for the treatment of benign
      prostate hyperplasia(BPH). METHODS: One hundred and seventy-nine patients with
      BPH were treated by the combined use of transurethral electrovaporization
      ablation of the prostate(TUVP) and transurethral resection of the prostate(TURP).
      RESULTS: The procedure was successful and the results were satisfactory, with
      little bleeding and no serious complication. IPSS decreased from 29.0
      preoperatively to 7.6 postoperatively (P < 0.05) and Qmax increased from 5.8 ml/s
      preoperatively to 14.8 ml/s postoperatively(P < 0.05). CONCLUSIONS: The combined
      use of TUVP and TURP is a safe, effective and ideal method for the treatment of
      BPH.

PMID- 14689890
TI  - [Experimental study of contralateral testicular changes after unilateral
      testicular torsion in rats].
AB  - OBJECTIVE: To study the changes of the contralateral testicular histology and
      germ cell apoptosis after unilateral testicular torsion (UTT) and to determine
      whether the contralateral testis is injured or not. METHODS: Sixty SD male rats
      were divided into control group (12 rats) and experimental group(48 rats). The
      former underwent sham operation of the left testis under general anaesthesia. The
      latter underwent left testis torsion(720 degrees) for 6 h, and then 4 of them
      were sacrificed and the other 44 were subdivided into the torsed testis untwisted
      group (22 rats) and the torsed testis removal group (22 rats), 7-8 rats were
      sacrificed and both testes (twisted and untwisted) were removed 1 day, 1 week and
      4 weeks after surgery. All testes underwent histological and germ cell apoptosis
      examination. RESULTS: There were significant histological changes in the
      contralateral testis, and the germ cell apoptosis was increased greatly in the
      contralateral testis. CONCLUSIONS: UTT can cause contralateral testicular injury,
      whose mechanism may be related to reperfusion, and torsed testis removal can
      prevent or reduce damage to the contralateral testis.

PMID- 14689891
TI  - [Studies on dihydrotestosterone-binding capacity in prostate tissue].
AB  - OBJECTIVE: To explore the effect of the binding ability of the
      dihydrotestosterone(DHT) in prostate. METHODS: Twenty-two normal prostate tissues
      taken from accident-death corpses without serious diseases, and cytosolic and
      nuclear fractions were prepared with all the endogenous hormone removed from the
      cytosolic and nuclear fractions by ether stripping. The content of the bound 3H
      DHT was assayed by adding 3H-DHT. RESULTS: The average DHT-binding capacity of
      the DHT-binding protein in prostate was (0.0263 +/- 0.0047) nmol/g wet tissue.
      The DHT-binding capacities of cytosolic and nuclear fractions were (0.0103 +/-
      0.0015) nmol/g wet tissue and (0.0155 +/- 0.0035) nmol/g wet tissue respectively,
      and the difference between them was very significant(P < 0.01). CONCLUSIONS: The
      DHT-binding capacity of the DHT-binding protein in prostate is high and
      maintaining the high DHT level facilitates the effect of DHT.

PMID- 14689892
TI  - [Effect of sildenafil ciltrate on the sexual activities of male rats].
AB  - OBJECTIVE: To obtain related pharmacodynamic data for the clinical experiment by
      observing the sexual activities of male rats after using sildenafil ciltrate
      through stomach irrigation. METHODS: Forty male Sprague-Dawley rats were
      distributed into 4 groups with different dosages (control with distilled water,
      low dosage: 0.08%, medium dosage: 0.24% and high dosage: 0.72%). After the male
      Sprague-Dawlay rats were mated with their female counterparts in pairs, the
      latent period of chasing, the frequencies of chasing in 60 minutes, the latent
      period of intercourse and the frequencies of intercourse in 60 minutes were
      recorded. RESULTS: Compared with the control, the frequencies of chasing were
      significantly increased and the latent periods of chasing were significantly
      shortened in both high dosage and medium dosage groups after using sildenafil (P
      < 0.01); The frequencies of intercourse in 60 minutes were significantly
      increased and the latent periods of intercourse were significantly shortened in
      all the groups after the use of sildenafil. CONCLUSIONS: The sexual activities of
      male rats treated with sildenafil were significantly activated.

PMID- 14689893
TI  - [Effects of jing'an capsule on rat sperm quality].
AB  - OBJECTIVE: The effects of Jing'an capsule on the quality of rat sperm were
      studied to supply data for its safe clinical use. METHODS: Eighty SD male rats
      were evenly and randomly divided into three test groups and one control group.
      Then the test groups were continuously given Jing'an capsule at different
      dosages: 557.1 mg/kg, 5,571 mg/kg or 11,420 mg/kg and the control group was given
      starch (20 g/L). Sixty days later, one of the epididymides, the sperm density was
      made and the sperm motility and morphology were investigated. The data obtained
      were analyzed by ANOVA, chi 2 test and Kruskal-Wallis test. RESULTS: The sperm
      density, motility and morphology were variable at different dosages. Compared
      with the control, the sperm density increased significantly at the dosage of
      557.1 mg/kg(P < 0.05), and a significant decrease was observed in the sperm
      density and motility (P < 0.05) at the dosage of 11,420 mg/kg. Although the rate
      of abnormal sperm morphology decreased at the dosage of 557.1 mg/kg and increased
      at the dosage of 5,571 mg/kg or 11,420 mg/kg compared with the control, there was
      no statistic significance(P < 0.05). CONCLUSIONS: A low dosage of Jing'an capsule
      might ameliorate the quality of sperm, while a high dosage could do damage to
      sperm.

PMID- 14689894
TI  - [Examination and significance of semenial prostate specific antigen in infertile
      patients].
AB  - OBJECTIVE: To investigate the significance of prostate specific antigen (PSA)
      examination in seminal plasma of infertile patients. METHODS: Eighty-five
      infertile patients were collected randomly. The level of PSA in seminal plasma
      was detected by ELISA method. The correlations between PSA and several seminal
      parameters including sperm density, motility and acid phosphatase (ACP) were
      analyzed. RESULTS: The PSA, ACP concentrations and sperm motility in 65 cases of
      abnormal liquefaction patients were obviously lower than those in normal
      liquefaction patients(P < 0.01). But there were no significant differences in
      sperm density among the three groups(P > 0.05). PSA levels were significantly
      correlated with ACP and sperm motility(P < 0.01). CONCLUSIONS: The seminal PSA in
      infertile patients is markedly correlated with semen liquefaction. The abnormal
      quality and quantity of PSA can result in a depression of sperm motility and
      subinfertility.

PMID- 14689895
TI  - [Prevalence and drug tolerance of mycoplasma in patients with urogenital
      inflammation].
AB  - OBJECTIVE: To observe the prevalence and drug tolerance of mycoplasma(Ureaplasma
      urealyticum and Mycoplasma hominis) in patients with urogenital inflammation.
      METHODS: Three thousand and fifty-five patients with urogenital inflammation such
      as non-gonococcal urethritis(NGU), chronic prostatitis or pelvic inflammation
      from 1999 to 2003 were included. The results of mycoplasma culture and drug
      sensitivity test were analyzed. RESULTS: A total of 992(32.5%) cases were
      mycoplasma positive in the 3,055 patients, and there was no significant
      difference in the yearly positive percentage in the 5 years (P < 0.05). Among
      them, 701(70.7%) were infected with Ureaplasma urealyticum, 44(4.4%) with
      Mycoplasma hominis, and 247(24.9%) with both Ureaplasma urealyticum and
      Mycoplasma hominis, the Ureaplasma urealyticum infection rate being much higher
      than that of Mycoplasma hominis and mixed infection (P < 0.01). The high colony
      counting(> or = 10(4) cfu/ml) in Ureaplasma urealyticum infection patients
      accounted for 76.7%, while Mycoplasma hominis infection represented only 18.2%.
      The results of drug tolerance test showed a higher sensitivity to doxycycline,
      pristinamycin, josamycin and tetracycline (94.3%, 96.6%, 86.5% and 97.4%
      respectively), and a lower sensitivity to erythromycin and ofloxacin (54.8% and
      29.4% respectively). CONCLUSIONS: Ureaplasma urealyticum and Mycoplasma hominis
      should be detected simultaneously and the drug tolerance test is needed for the
      selection of appropriate antibiotics.

PMID- 14689896
TI  - [Detection and significance of succinate dehydrogenase of sperm mitochondria].
AB  - OBJECTIVE: To detect succinate dehydrogenase (SDH) of sperm mitochondria by an
      improved method, and to evaluate the relationship between SDH and the motility
      and viability of sperm. METHODS: In 46 fertile and infertile men (aged from 25 to
      36), the motility, viability and mitochondrial SDH of sperm were detected by
      computer-assisted semen analysis system, dead/live sperm molecular fluorescent
      probe and an improved cytochemical method. Then, the correlation between the
      motility and viability of sperm and the positive percentage of sperm
      mitochondrial SDH were analyzed. RESULTS: In the 46 fertile and infertile men,
      the motility and viability of sperm were (67.33 +/- 7.37)% and (79.78 +/- 7.65)%,
      and the positive percentage of sperm mitochondrial SDH was (74.74 +/- 8.29)%. The
      motility and viability of sperm and positive percentage of sperm mitochondrial
      SDH had significant correlation (r = 0.901, P < 0.01; r = 0.876, P < 0.01; r =
      0.917, P < 0.01). CONCLUSIONS: Detection of sperm mitochondrial SDH has
      significance in evaluation of sperm mitochondrial function and may serve as an
      assisted marker of sperm viability.

PMID- 14689897
TI  - [Animal models for erectile dysfunction researches].
AB  - Knowledge about the physiology, pathophysiology and pharmacology of human
      erection is mostly obtained through researches on animals and animal models.
      However each animal or animal model has its own advantages and limitations and no
      single animal model completely satisfies all studies. The credibility of the
      research results primarily lies on the rational selection of animal models. So it
      is very important to recognize the characteristics of every animal and animal
      model and select appropriate models for studies. This article is meant for a
      review: the characteristics of the animals widely used for erectile dysfunction
      researches, the selection of appropriate animals for researches, and the methods
      and mechanisms of making the animal models of the clinically ever-present kinds
      of erectile dysfunction.

PMID- 14689898
TI  - [Advances in researches on lactate dehydrogenase-C4 isozyme].
AB  - Lactate dehydrogenase-C4 isozyme has been widely studied as the sperm-specific
      antigen in the research of the contraceptive vaccine. Developmental and testis
      specific expression of the LDH-C gene requires mechanisms for activation in germ
      cells and repression in somatic cells. LDH-C promoter, several transcription
      factors and methylation of CpG dinucleotides have been proved of governing action
      on LDH-C gene transcription. The strategy is to induce antibodies in the female
      reproductive tract against LDH-C antigens at a sufficient level to block
      fertilization. Chemically modified LDH-C4 offers a potential application in the
      induction of infertility of homologous species in marked contrast to native LDH
      C4. In addition, advances are being made in researches on the male contraceptive
      vaccine and synthetic peptide immunocontraceptive.

PMID- 14689899
TI  - [Advances in epidemiology, diagnosis and treatment of genital herpes].
AB  - Changes in sexual behavior may constitute an important contribution to relative
      increase in genital herpes. Many research results suggest that HSV-2 plays a big
      part in the transmission of HIV infection. There is an urgent need to identify
      effective HSV-2 control measures in order to reduce HIV incidence. The detection
      of HSV-2-specific antibodies in serum is especially useful and reliable. During
      the past 2 decades, selective and specific inhibitors of replication have been
      developed. Such agents as acyclovir, valaciclovir and famciclovir, have reduced
      the time of healing and the possibility of virus excretion. Efforts have been
      made in different directions including the exploration of new targets for
      antiviral chemotherapy, the use of immunomodulators and the development of
      specific vaccines.

PMID- 14689900
TI  - [Advances in studies of Chinese herbs for improving relaxability of corporal
      smooth muscle].
AB  - Erectile dysfunction (ED) is a commonly and frequently encountered disease among
      middle-aged and old males. The traditional Chinese medicine has a long history of
      medical treatment for ED has been focusing too much on clinical experience
      researches, without obtaining sufficient evidence for the curative effect of
      related traditional medicines. Recently, with important breakthroughs the
      researches on the molecular biochemical mechanisms of erection,
      sildenafil(Viagra), a phosphodiesterase type 5 (PDE5) inhibitor, has been
      developed, and exciting progress achieved in the treatment of ED with Chinese
      herbal medicine and the presentation of the pharmacological mechanism. This
      article presents an overview on recent advances in the studies of ED treatment
      with traditional Chinese medicine.

PMID- 14689901
TI  - [Chinese traditional medicine yi kang ling to treat immunity infertility caused
      by anti-sperm antibody: the experimental research. I].
AB  - OBJECTIVE: To observe the effects of Chinese traditional medicine Yi Kang Ling
      (YKL) on immunity infertility caused by anti-sperm antibodies (AsAb). METHODS:
      Based on the animal model of immunity infertility, seventy-five pairs of New
      Zealand rabbits were divided into three groups: YKL treatment group (sub-divided
      into mini-, midi- and maxi-dosage groups), prednisone treatment group and non
      treatment group. Five pairs of normal rabbits were used as control. The AsAb from
      the rabbit serum were detected on the 15th, 30th and 45th day of treatment
      respectively. The sperm density, activity, the mobility and AsAb of seminal
      plasma from the obedient rabbits were determined. RESULTS: Statistics showed that
      on the 45th day in mini- and maxi-YKL and prednisone treatment groups the
      positive serum AsAb reversing ratio reached 100%, and the seminal plasma AsAb
      reversing ratios were 85% in mini- and maxi-YKL group, 83% in midi-YKL and
      prednisone groups, while in non-treatment group the reversing ratios of the
      positive serum AsAb and seminal plasma AsAb were only 20% and 25% respectively.
      There were also remarkable differences (P < 0.05) in both serum AsAb and seminal
      plasma AsAb on the 45th day of treatment between YKL, prednisone treatment groups
      and the non-treatment group. CONCLUSIONS: YKL can effectively reverse the AsAb
      positive results, hence increasing sperm mobility and improving sperm quality.

PMID- 14689902
TI  - [Practice and experience of the scientific research management].
AB  - The practice and experience of the scientific research management in Nanjing
      General Hospital from 1997 to 2002 is summarized in this review. By presenting
      the achievement gained in the past 6 years, the author prove to the scientific
      research managers that the effective manage thought is the key of scientific
      research management, and also expatriate the experience of the key points
      management in the management of scientific research subjects.

PMID- 14689903
TI  - [Positron emission tomography: a revolution in oncology?].

PMID- 14689904
TI  - [Helicobacter pylori. Prevalence diminishes in industrialized countries].

PMID- 14689905
TI  - [Thalidomide and others: new treatment for myeloma].

PMID- 14689906
TI  - [Abdominal hernia. 15 years of major progress].

PMID- 14689907
TI  - [How is an abdominal hernia formed?].
AB  - Abdomen can be compared in broad outline with an irregular cylinder, limited at
      the top by the diaphragm and below by the pond. The walls of this cylinder are
      musculo-aponevrotic and present "zones of weakness" seats of the hernias of the
      abdominal wall. We propose a topographic anatomical approach of abdominal
      hernias.

PMID- 14689908
TI  - [Diagnosis and complications of inguinal hernias].
AB  - The medical history and the physical examination are the most important parts of
      the diagnosis of groin adults' hernias. The examination will be done the patient
      initially stand up. The doctor examines the external inguinal ring, the internal
      inguinal ring and the floor of the inguinal canal. Usually, this exam will be
      sufficient for a groin hernia diagnosis. However this physical exam will be
      insufficient in more than 50% for the diagnosis of the exact type of hernia. This
      diagnosis will be difficult with a pain syndrome without physical examination
      anomalies. Much other diagnosis must be considered before surgical exploration.
      In these cases, ultrasonography could be a good opportunity, like in cases of
      unexplained groin tumours. TDM is a good exam, only to explore the content and
      the parietal defect of large, old, fixed hernias. In fact, it is important to
      remember that groin hernia could be a symptom of colon, rectum, or prostatic
      diseases, secondary to intraabdominal pressure.

PMID- 14689909
TI  - [Surgery for inguinal hernia: indications and operative principles].
AB  - During the last century, many surgical techniques have been reported for inguinal
      hernia repair. The goal of theses methods is to repair or reinforce the posterior
      wall of inguinal canal. The raphies performed by suturing and closing the
      inguinal ring may lead to excessive tension resulting in pain and recurrence. The
      use of prosthetic mesh reinforces the posterior wall and allows tension-free
      repair whether performed by inguinal route or laparoscopically. No consensus has
      yet been reached about the best surgical approach to inguinal hernia repair in
      view of the literature (especially randomised-controlled trials). Mesh repairs
      are associated with a low recurrence rate. Laparoscopy seems not to be superior
      to open mesh repair. Therefore, it is not possible to use only a single technique
      and the surgeon must adjust the choice of repair to each patient.

PMID- 14689910
TI  - [Postoperative complications after inguinal hernia repair].
AB  - Most complications after inguinal hernia repair are transitory and do not affect
      the functional outcome. On the other hand, some last longer or become permanent
      and will be a daily problem for the patient as well as the attending physician.
      Most prevalent and difficult to treat is pain. Bruising and hematoma are banal
      and usually resolved spontaneously. Infection can prolong care and promote
      recurrence. Recurrence seems less frequent after mesh repair, whether by
      traditional or laparoscopic surgery. Potential complications specific to
      laparoscopic hernia repair, rare but sometimes severe, must be weighed against
      the benefits expected by the patient. The patient must be duly informed of the
      risks and advantages of each technique, whether traditional, laparoscopic, with
      or without prosthetic material.

PMID- 14689911
TI  - [Is it always necessary to operate on inguinal hernias?].

PMID- 14689912
TI  - [Inguinal hernias in children].
AB  - The inguinal hernia repair account among surgical procedures the most frequently
      performed in children. Most inguinal hernias in infants and children are indirect
      due to patent processus vaginalis. Failure of closure of the processus vaginalis
      accounts for nearly all the inguino scrotal abnormalities seen in infancy and
      childhood. In little girls, the processus (canal de Nuck) may remain patent and
      may allow the ovary and fallopian tube to enter the inguinal region.
      Incarceration represents the most common complications associated (30 per-cent
      during the first year of life). Consequences concern in the first place the
      testicular blood supply before to interest the vitality of the incarcerated
      intestine. The surgically repair is recommended shortly after the diagnosis. The
      concurrence rate of recurrent inguinal hernia after uncomplicated inguinal hernia
      repairs is generally reported at 0.5-1 per cent, increasing for premature infant
      and complicated inguinal hernia.

PMID- 14689913
TI  - [Umbilical hernia].
AB  - Frequent and well known pathology, umbilical hernias are different if they occur
      in children or adults. Embryology and anatomy are necessary to understand all
      mechanisms which can explain a weakness or non complete closure of the umbilical
      ring. An umbilical hernia during infancy, is congenital. The diagnosis is easy,
      as well as its surgical treatment, usually without recurrence. In adulthood such
      an hernia has an acquired origin. Its treatment is often more complex, especially
      in obese middle-aged multiparous women, and cirrhotics. The most important is to
      choose the right time for surgery before complications occur: strangulation or
      umbilical ruptures in cirrhotics, above all with ascites. In these cases, the
      rate of morbidity and mortality is high, and recurrences as well.

PMID- 14689914
TI  - [Eventration of the abdominal wall].
AB  - Incisional hernia is one of the most common complications after abdominal
      surgery, secondary to postoperative infection and intraabdominal hyperpressure.
      The chronicity with gradual increase in size of some of these hernias is such
      that the hernial ring enlarges resulting in a real parietal defect, the herniated
      organs can be strangulated and the poor abdominal motility alters the respiratory
      function. All incisional hernias require surgical repair, except small
      asymptomatic hernias. Surgical treatment depends on several factors, especially
      the size of the defect: Simple hernioplasty can be recommended for small hernias
      (ring < 5 cm); for large hernias, the reinforcement of the abdominal wall with a
      prosthesis is mandatory for long term successful repair. The type and the site of
      the prosthesis depend on the surgical technique.

PMID- 14689915
TI  - [Diaphragmatic hernia].
AB  - A diaphragmatic hernia is the protrusion of abdominal contents into the thoracic
      cavity, via a hole in the diaphragm, which either presence or size is abnormal.
      Congenital hernias are rare and often diagnosed at birth. Adults are diagnosed
      accidentally. Symptoms can be digestive or respiratory, and the risk of volvulus
      calls for surgery. Diaphragmatic ruptures are seen more often, and are a
      consequence of violent thoraco-abdominal trauma, or penetrating wound. They
      should be treated surgically in emergency, but the operation can be delayed if
      they are not diagnosed at once. Videosurgery has been used more and more often
      recently to treat diaphragmatic hernias.

PMID- 14689916
TI  - [Diaphragmatic eventration which is neither hernia nor rupture].

PMID- 14689917
TI  - [Abdominal hernias in MEDLINE].

PMID- 14689918
TI  - [Patient memo. A cure for hernia].

PMID- 14689919
TI  - [Type 1 and 2 diabetes in children and adults. Third part: diabetic
      complications].

PMID- 14689920
TI  - [Complications of immobility and bedrest. Prevention and management].

PMID- 14689921
TI  - [Medical ethics and deontology; patient rights. Diagnostic problems, with respect
      to the person and to death].

PMID- 14689922
TI  - [Anxiety and adjustment disorders].

PMID- 14689923
TI  - [Acute respiratory distress in the newborn, the child and the adult. Foreign
      bodies of the upper respiratory tract. 2nd part: in the infant and child].

PMID- 14689924
TI  - [In the 19th center, physiognomy of scrofulas].

PMID- 14689925
TI  - The burden of disease. HIV, TB, malaria and hepatitis.

PMID- 14689926
TI  - TB treatment evolves.

PMID- 14689927
TI  - Targeting persistence: the next frontier in TB drug development.

PMID- 14689929
TI  - The ecology of drug resistance.

PMID- 14689928
TI  - Vaccinate to prevent hepatitis B.

PMID- 14689930
TI  - HCV snapshots: macro to micro.

PMID- 14689931
TI  - TB is about people.

PMID- 14689932
TI  - Targeted therapies - First International Congress.

PMID- 14689933
TI  - Central European Lung Cancer Conference - Eighth International Meeting.

PMID- 14689934
TI  - International Society for Oncodevelopmental Biology and Medicine - XXXth Meeting.

PMID- 14689935
TI  - Medicinal Chemistry - XVIIth International Symposium.

PMID- 14689937
TI  - Antimicrobial and antiviral agents.

PMID- 14689936
TI  - Pulmonary disease.

PMID- 14689938
TI  - British Pharmacology Society - Autumn Meeting 2002.

PMID- 14689940
TI  - Bionetwork 2002: The Biopharm Licensing and Partnering Forum.

PMID- 14689939
TI  - European CEO and Investor Conference - Third Annual BIA Meeting.

PMID- 14689941
TI  - Strategies for successful collaborations and alliances in drug discovery.

PMID- 14689942
TI  - Evolution 2002 summit.

PMID- 14689943
TI  - Global drug development.

PMID- 14689944
TI  - A new era in pharma.

PMID- 14689946
TI  - New drugs.

PMID- 14689945
TI  - Society for Neuroscience - 32nd Annual Meeting.

PMID- 14689947
TI  - Ischemia & Alzheimer's disease.

PMID- 14689948
TI  - The glutamatergic system.

PMID- 14689949
TI  - Anti-aging therapies - SMi Conference.

PMID- 14689950
TI  - American College of Gastroenterology - 67th Meeting.

PMID- 14689951
TI  - Evolution of COX isozymes and their inhibitors - William Harvey Research
      Conference.

PMID- 14689952
TI  - Chemical genomics - Active Communications International Conference.

PMID- 14689953
TI  - Genomex 2002.

PMID- 14689954
TI  - Sixth COngress of the European Federation of Neurological Societies.

PMID- 14689955
TI  - Diabetes 2002 - SMi Conference.

PMID- 14689956
TI  - Advances in cardiovascular drug development. Biomarkers, surrogates and clinical
      progress.

PMID- 14689957
TI  - EUFEPS 2002 - new safe medicines faster.

PMID- 14689958
TI  - Infectious Diseases Society of America - 40th Annual Meeting.

PMID- 14689959
TI  - Bilateral buccal radicular groove in maxillary incisors: case report.
AB  - AIM: To present the rare localization of a radicular groove on the buccal aspect
      of a tooth and to discuss the pathology and management of the concomitant endo
      periodontal defect. SUMMARY: Bilateral buccal radicular grooves were found on the
      maxillary central incisors of a 60-year-old female Caucasian. One groove was
      associated with deep local pocketing resulting in pulp necrosis and the formation
      of a periodontal-endodontic lesion. After endodontic treatment of the affected
      tooth, periodontal surgery was performed during which an apicoectomy was carried
      out on the root-filled tooth. Both the buccal grooves were removed by grinding,
      the roots were planed with curettes and a guided-tissue regeneration technique
      applied using amelogenin (Emdogain, Biora, Sweden). Following a period of 2
      years, re-examination showed excellent healing with the complete elimination of
      the periodontal pocket on both incisors and significant radiographic evidence of
      bone regeneration. KEY LEARNING POINTS: Deep radicular grooves can predispose to
      pulp necrosis and the establishment of combined periodontal-endodontic lesions.
      Evaluation of clinical signs and appropriate diagnostic tests are of paramount
      importance in order to prevent incorrect diagnosis and treatment. Endodontists
      must be capable of performing advanced periodontal regeneration techniques during
      endodontic surgery.

PMID- 14689960
TI  - Focal cemento-osseous dysplasia involving a mandibular lateral incisor.
AB  - AIM: To report a case of focal cemento-osseous dysplasia (FCOD) affecting a
      single tooth misdiagnosed as an inflammatory periapical lesion. SUMMARY: The
      patient, a black 47-year-old woman complained of pain affecting the right side of
      the mandible. Routine X-ray examination discovered a periapical radiolucency on
      the mandibular left lateral incisor (tooth 32), which was otherwise normal and
      not carious. As the response of this tooth to a vitality test was doubtful, the
      lesion was diagnosed as a periapical granuloma or cyst secondary to pulpal
      necrosis. Endodontic treatment and curettage of the periapical lesion were
      performed, and histological examination of the curettage material revealed a
      localized osseous dysplasia. KEY LEARNING POINTS: FCOD may rarely affect only one
      tooth, resembling a periapical granuloma or cyst. Careful diagnosis is of
      paramount importance in cases of questionable periapical lesions affecting normal
      looking teeth, before beginning treatment. FCOD generally requires no treatment.
      Biopsy is warranted in case of doubt.

PMID- 14689962
TI  - Retraction of publication.

PMID- 14689963
TI  - Add liability issue to 'to-do' list.

PMID- 14689961
TI  - Diagnosis and root canal treatment of a mandibular second premolar with three
      root canals.
AB  - AIM: To present a case of a mandibular second premolar with three root canals.
      SUMMARY: An accurate diagnosis of the morphology of the root canal system is a
      prerequisite for successful root canal treatment. A review of the literature
      reveals a low incidence of all types of premolars with three root canals.
      Diagnostic means such as preoperative radiographs and examination of the pulp
      chamber floor aid the location of root canal orifices. The diagnostic and
      therapeutic problems concerning premolars with unusual anatomy are described on
      the basis of a clinical example. A case report describes the successful treatment
      of a mandibular second premolar with three root canals. KEY LEARNING POINTS:
      Clinicians should be aware of unusual root canal anatomy in mandibular premolars.
      Radiographs exposed at two different horizontal angles and their careful
      interpretation facilitate the search of additional root canals. The use of
      magnification and additional lighting are recommended for the clinical
      examination of the pulpal floor.

PMID- 14689964
TI  - Unite for change.

PMID- 14689965
TI  - Medication safety issue brief. Series II, Part 6: Tapping into your staff's
      energy.
AB  - The front-line workers in a hospital are its greatest resources, particularly
      when it comes to improving safety. After all, they know the crucial details about
      day-to-day operations and can offer innovative solutions to problems. But staff
      members don't always feel comfortable getting involved in change. To tap this
      hidden well of talent, hospitals leaders should train staff in systems thinking,
      cultivate a culture of safety and make it easy for employees to contribute their
      ideas.

PMID- 14689966
TI  - Practical ethics. Say ah! or nah! to a spa?

PMID- 14689967
TI  - Lateral phosphorylation propagation: an aspect of feedback signalling?

PMID- 14689968
TI  - Arsenic trioxide enhances radiation response of 9L glioma in the rat brain.
AB  - Arsenic trioxide (ATO) at low doses induces leukemia cells to undergo apoptosis
      and at higher doses causes blood flow to solid tumors to shut down. To determine
      whether a potential synergistic interaction exists between ATO at the non-toxic
      dose level in the rat and radiation, the present study was carried out with
      orthotopic 9L malignant gliomas growing in the brains of rats. Animals died
      within 50 days of treatment when 12-day-old 9L gliomas growing in the brain of
      Fischer rats were treated with either the drug alone (8 mg/kg) or radiation alone
      (25 Gy). In contrast, the overall tumor cure rate exceeded 50% at a follow-up
      time of 120 days after the combined treatment with radiation and ATO. Long-term
      surviving animals showed no clinical or disproportionately enhanced
      histopathological changes in the brain parenchyma. Early changes in tumor
      physiology showed that the vascular leakage of FITC-dextran conjugates was
      apparent within 8 h of drug administration. Last, the use of diffusion magnetic
      resonance imaging as an early surrogate marker of therapeutic efficacy
      corroborated the effects of drug with and without radiation on brain histology
      and animal survival.

PMID- 14689969
TI  - Employers embrace disease management despite limited proof of benefits.

PMID- 14689970
TI  - Casualty of court. Oregon verdict sends message: 'Watch out for juries'.

PMID- 14689971
TI  - Abstracts of the British Thoracic Society winter meeting. 3-5 December 2003,
      London, United Kingdom.

PMID- 14689972
TI  - [Excretion of catecholamines in development of the opium and alcohol abstinence
      syndrome and in post-abstinence period].
AB  - Excretion of catecholamines has been studied in patients with opium narcotic and
      alcoholic dependence in developmental dynamics of the opium and alcoholic
      abstinence syndrome and in the postabstinence period. It has been revealed that 8
      10 h after cessation of the psychoactive substances (the preabstinence period)
      the level of excretion of adrenaline [A], dioxyphenylalanine [DOPA], dopamine
      [DA] and, to the greatest extent, of noradrenaline [NA] especially in patients
      with alcoholic dependence decreases in comparison with the control variant. As
      compared to the control variant the acute form of abstinence syndrome (1-3 days
      after cessation of the psychoactive substances is characterized by the higher
      level of the A and DA excretion and the lower level of the NA excretion
      (especially in patients with opium narcotic dependence). As compared to the
      preabstinence period under conditions of the acute abstinence syndrome there is
      an essential increase in the level of the A, NA, DOPA and DA excretion. As
      compared to the control variant the postabstinence period (10-20 days after
      cessation) is characterized by the lower level of the NA excretion, especially in
      patients with alcoholic dependence, and of DOPA. The level of DA decreases in
      patients with alcoholic dependence. As compared to the acute abstienence syndrome
      the postabstinence period differs by the lower level of the A, NA (especially in
      patients with alcoholic dependence), DOPA (only inpatients with alcoholic
      dependence) and of DA excretion.

PMID- 14689973
TI  - Is there a room for vitamins?

PMID- 14689974
TI  - Florida Dental Association membership directory.

PMID- 14689975
TI  - Abstracts of the XIIIth International Symposium on Atherosclerosis. September 28
      October 2, 2003. Kyoto, Japan.

PMID- 14689976
TI  - Abstracts of the American Society for Histocompatibility and Immunogenetics 29th
      annual meeting. October 28-November 1, 2003. Miami Beach, Florida, USA.

PMID- 14689977
TI  - Abstracts of the Bariloche Protein Symposium. Argentine Society for Biochemistry
      and Molecular Biology XXXIX annual meeting and Biophysical Society of Argentina
      XXXII annual meeting. November 17-21, 2003, San Carlos de Bariloche, Argentina.

PMID- 14689978
TI  - Abstracts from the 14th International Symposium on Amyotrophic Lateral
      Sclerosis/Motor Neuron Disorders. Milan, Italy, 17-19 November 2003.

PMID- 14689979
TI  - Abstracts of the 7th World Congress on Sleep Apnea. June 29-July 3, 2003.
      Helsinki, Finland.

PMID- 14689980
TI  - Abstracts from the 27th Congress of The Scandinavian Society of Anaesthesiology
      and Intensive Care Medicine. August 16-20, 2003, Helsinki, Finland.

PMID- 14689981
TI  - Abstracts of the European Association of Nuclear Medicine. Amsterdam, The
      Netherlands, 23-27 August 2003.

PMID- 14689982
TI  - The trends in modern psychiatry are complex.

PMID- 14689983
TI  - [Dermatologic Days of Paris. 2-6 December 2003, Paris, France. Abstracts].

PMID- 14689984
TI  - Proceedings and abstracts of the International Symposium on Recent Advances in
      Molecular Genetics of the Maghreb and Middle East Populations. Hammamet, Tunisia,
      16-20 December 1997.

PMID- 14689985
TI  - Abstracts of the Irish Endocrine Society 28th Annual Meeting. 7-8 November 2003.

PMID- 14689987
TI  - Abstracts of the Irish Thoracic Society Annual Meeting. 14-15 November 2003,
      Belfast.

PMID- 14689988
TI  - The Digital Future and Radiation Oncology. Abstracts of the Canadian Association
      of Radiation Oncologists annual meeting. October 3-5, 2003, Montreal, Canada.

PMID- 14689986
TI  - Psychiatric evidence on trial.

PMID- 14689989
TI  - Abstracts of the British Geriatrics Society spring meeting. 10-11 April 2003,
      Aberdeen, United Kingdom.

PMID- 14689990
TI  - Bibliography. Current world literature.

PMID- 14689991
TI  - Photon attenuation, natural radioactivity content and radon exhalation rate of
      building materials.
AB  - High concentrations of natural radionuclides in building materials can result in
      high dose rates indoors, from both internal and external exposure. In dose
      calculations, the main radionuclides of interest are 226Ra, 232Th and 40K.
      Usually much attention is paid to 226Ra due to 222Rn exhalation and the
      subsequent internal exposure. Other radionuclides of the uranium series such as
      238U and 210Pb, emitting low energy photons are not usually determined and an
      assumption of radioactive equilibrium is made. The above assumption is seldom
      checked mainly because of the difficulties in the gamma-spectroscopic analysis of
      low energy photons. For the determination of radionuclides emitting low-energy
      photons, in samples like building materials where intense self-absorption of the
      photons exists, a method for self-absorption correction has been developed. The
      method needs as input the linear attenuation coefficient mu for the material
      under analysis. This paper presents: 1. Correlations in the form mu = f(rho,E)
      developed for the estimation of the linear attenuation coefficient mu (cm(-1)),
      as a function of the material packing density p (g cm(-3)) and the photon energy
      E (keV), for building materials as well as other materials of environmental
      importance. 2. Gamma-spectroscopic analysis techniques used for the determination
      of 238U, 226Ra, 210Pb, 232Th and 40K in environmental samples, together with the
      results obtained from the analysis of building materials used in Greece, and
      industrial by-products used for the production of building materials. Among the
      techniques used, one is based on the direct determination of 226Ra and 235U from
      the analysis of the multiplet photopeak at approximarely186 keV. 3. Results from
      radon exhalation measurements of building materials such as cement and fly-ash
      and building structures conducted in the radon chambers in our Laboratory. Based
      on the above results, dosimetric calculations are also reported.

PMID- 14689992
TI  - Survey of natural and anthropogenic radioactivity in environmental samples from
      Yugoslavia.
AB  - The radioactivity of 238U, 226Ra, 232Th, 40K and 137Cs in sediments, soil, turf
      and honey from Serbia and Kosovo (Yugoslavia) was measured using gamma and alpha
      spectrometry in order to estimate the radiation hazard from natural and man-made
      sources, as well as to compile a database for radioactivity levels in those
      regions. One sample, collected in the vicinity of a "depleted uranium" (DU) shell
      of the recent Balkan war, revealed a high 238U activity and a non-natural
      235U/238U activity ratio, confirming therefore its anthropogenic origin. However,
      some other soil samples coming from characteristic DU craters did not show any
      characteristic level of radioactivity. The other sediment and turf samples taken
      all around the country show low radioactivity levels for all the isotopes here
      considered. With the aim of obtaining some indication about radioactivity
      migration in the food chain, several honey samples have been examined too. All
      samples show very low radioactivity content, often indistinguishable from natural
      background.

PMID- 14689993
TI  - Radon flux at King George Island, Antarctic Peninsula.
AB  - Fluxes of 222Rn from the ice-free terrain to the atmosphere were measured
      directly, for the first time, at the Brazilian Antarctic Station Ferraz during
      the summer field campaign of 1998/99. Average value for the flux was 7.7 +/- 4.8
      x 10(-2) atoms cm(-2) s(-1) and it ranged between 0.21 x 10(-2) atoms cm(-2) s(
      1) and 28 x l0(-2) atoms cm(-2) s(-1). The average flux of 220Rn was estimated to
      be 23 atoms cm(-2) s(-1), using a combination of two techniques: nuclear track
      detection and alpha spectrometry of radon daughters. It was found that the
      production of radon by uranium (41.54 + /-7.17 Bq kg(-1)) and thorium (57.97 +/-
      12.14 Bq kg(-1)) equivalent soil contents, and a diffusion coefficient derived
      from experimental data for the local terrain could account for this average flux.
      Nevertheless, the large surges of 222Rn in the atmosphere frequently observed for
      that area could not be explained by this flux only.

PMID- 14689994
TI  - Effects of different deposition models on the calculated dose conversion factors
      from 222Rn progeny.
AB  - Regional lung deposition for radon progeny (size range, 1 nm to 1000 nm,
      monodispersed) has been determined employing Gormley-Kennedy, Ingham, Cohen
      Asgharian and Yu-Cohen expressions (which describe diffusion deposition),
      together with Gurman and Cheng formulae for impaction and sedimentation,
      respectively. The deposition values have been compared with those obtained by
      using the algebraic expressions recommended by ICRP66. The behavior of the
      deposition curves for breathing rates of 0.45, 0.78 and 1.2 m3 h(-1) are similar,
      with a broad maximum in the range (1-100) nm. In the particle size range (1-100)
      nm, where the thermodynamic efficiency predominates, there are large differences
      among the five approaches, with ICRP values lying somewhat in the middle. Dose
      Conversion Factors nearly follow the regional deposition trends, Cohen-Asgharian
      and Ingham, close to the highest values, Yu-Cohen the lowest and ICRP, again,
      somewhat in the middle.

PMID- 14689995
TI  - A validation study for the transport of 134Cs to strawberry.
AB  - The paper presents results on model validation by field experiment for transport
      of 134Cs to strawberry. The transfer of 134Cs to herbaceous plants was
      investigated following a wet deposition after an acute release during 2000. Leaf
      to-fruit, soil-to-fruit and direct fruit pathways were examined. The available
      meteorological and local soil information together with the experimental data
      were taken into account by the model RUVFRU. The processes are described by first
      order differential equations. In the case of foliar contamination scenarios
      measured and calculated results for fruit are in good agreement. However, the
      results of soil contamination scenarios provide large differences of up to three
      orders of magnitude between model predictions and experimental values for either
      fruit or other parts of the plant. The bias could be explained by the
      underestimation of the interception of the plant at the beginning of the season,
      in the soil contamination scenario. The model output permits prompt assessment of
      emergency situations and provides aid making decisions concerning mitigation of
      the consequences of the accident.

PMID- 14689996
TI  - Level and origin of iodine-129 in the Baltic Sea.
AB  - Environmental samples, such as seawater, seaweed, lake water, lake sediment and
      grass collected from the Baltic Sea area were analyzed for 129I and 127I by
      radiochemical neutron activation analysis. In 2000, the concentration of 129I in
      the seawater from Borholm and Moen in the Baltic Sea has reached 6.0 x 10(-13)
      and 16 x 10(-13) g/l, respectively, these are more than two orders of magnitude
      higher than the global fallout level. The highest value of 270 x 10(-13) g/l
      being found in the seawater from the Kattegat. By comparison of the level of 129I
      in the lake water and precipitation in this region, it is estimated that more
      than 95% of 129I in the Baltic Sea originates from reprocessing emissions,
      especially from the French nuclear fuel reprocessing plant at La Hague. More than
      30% of 129I in the south Baltic and 93% in the Kattegat directly originates from
      the marine discharges of the European reprocessing plants.

PMID- 14689997
TI  - 234U and 238U isotopes in water and sediments of the southern Baltic.
AB  - The aim of this work was to determine the concentration of 234U and 238U and
      calculate the values of the 234U/238U activity ratio in waters and sediments from
      the various regions of the southern Baltic Sea: Gdansk Deep, Slupsk Narrow and
      Bornholm Deep. The concentration of uranium in analysed sediments from southern
      Baltic increase with core depth to what probably is connected with diffusion from
      sediments to water through interstitial water, where uranium concentration is
      much higher than in bottom water. The highest concentrations of uranium were
      observed in sediments of Slupsk Narrow (0.66-7.11 mg kg(-1) d.w.) and Slupsk Bank
      (0.61-6.93 mg kg(-1) d.w.), the lowest in sediments from Bornholm Deep (0.54-3.77
      mg kg(-1) d.w.). The 234U/238U activity ratio results indicated that the
      sedimentation of terrigenic material and Vistula River transport are the general
      sources of uranium in the southern Baltic sediments. The value of 234U/238U
      activity ratio in sediments from reduction areas from southern Baltic (Gdansk
      Deep and Bornholm Deep) indicated that reduction process of U(VI) to U(IV) and
      removing of anthropogenic uranium from seawater to sediments constitutes a small
      part only in Gdansk Deep.

PMID- 14689998
TI  - Search for radon sources in buildings--kindergartens.
AB  - In ten high radon level kindergartens, radon sources were sought by applying a
      combination of several radon measuring techniques: etched track detectors to
      obtain average indoor air radon concentration, continuous devices to record radon
      concentration and see its diurnal variation, and alpha scintillation cells to
      determine radon concentration in the air entering a room from cracks, holes and
      sinks in the floor and from under-floor channels. In three cases, a strong local
      radon source was identified while, in the others, the bad quality of the basic
      concrete slab was responsible for the high indoor radon concentration.

PMID- 14689999
TI  - Nutritional deterioration in cancer: the role of disease and diet.
AB  - AIMS: Under-nutrition is a major source of morbidity and mortality in cancer
      patients. This prospective, cross-sectional study aimed to evaluate the relative
      contributions of cancer staging, duration and diet on patients' nutritional
      deterioration. MATERIALS AND METHODS: We included 205 consecutive patients (133
      men and 72 women) with head and neck, gastro-oesophageal, colon and rectum
      cancer, age 53 +/- 12 (33-86) years, referred for radiotherapy (primary,
      adjunctive to surgery, combined with chemotherapy or with palliative intent). We
      registered clinical variables, nutritional status (percentage of weight loss,
      Patient-Generated Subjective Global Assessment and body mass index), nutritional
      requirements, usual diet intake (diet history) and current intake (24-h recall).
      RESULTS: In stage III and IV, we observed a significant decrease of usual and
      current energy and protein intake (P=0.002), which were not observed in stage I
      and II. Reduction in nutritional intake was influenced by disease duration
      (P=0.04), but when the latter was evaluated in a multivariate analysis, current
      dietary intake was associated only with staging (P=0.004), thus disclosing a
      distinct pattern of nutritional intake between stages and diagnosis. Using a
      general linear model, advanced staging showed the most significant association
      with nutritional depletion (P=0.0001). We also found significant associations for
      tumour location (P=0.001), disease duration (P=0.002), nutritional intake
      (P=0.003) and previous surgery or chemotherapy (P=0.02). Percentage weight loss
      showed a consistently superior performance with regard to clinical variables and
      ability to detect mild to extreme nutritional changes. Patient-Generated
      Subjective Global Assessment had a very high sensitivity and specificity, and a
      strong capacity for detecting patients at nutritional risk compared with body
      mass index. CONCLUSIONS: Nutritional depletion is multifactorial, dependent
      mainly on the tumour burden of the host. Percentage weight loss is a sensitive
      and specific tool that can screen and identify malnutrition effectively. Its
      joint use with Patient-Generated Subjective Global Assessment, which establishes
      boundaries for nutritional therapy, will optimise the efficacy of nutritional
      assessment and support in cancer patients.

PMID- 14690000
TI  - Timing of chemoradiotherapy and patient selection for locally advanced
      nasopharyngeal carcinoma.
AB  - AIMS: Predictors of outcome after radiotherapy alone for nasopharyngeal carcinoma
      (NPC) are now available from several retrospective studies. On the basis of
      these, it is theoretically possible to separate patients at risk of local failure
      from patients at risk of distant metastases (DM). According to classical
      principles of chemoradiotherapy timing, patients at risk of local failure would
      benefit mostly from concomitant chemoradiotherapy, whereas patients at risk
      distantly would benefit from sequential combinations. MATERIALS AND METHODS: We
      reviewed the literature on combined chemoradiotherapy treatment for
      nasopharyngeal carcinoma to assess whether timing of combined treatment matches
      pattern of failure. RESULTS: Available data show a significant overlap of
      activity, sequential treatments reducing local failure and concomitant treatments
      reducing DM. Therefore, in the individual patient, the strict adoption of
      traditional risk profiles in therapeutic decision-making may not fully exploit
      all the potential therapeutic effects derived from the maximal association of
      both sequential and concomitant therapies. CONCLUSION: Whether such combination
      is clinically worthwhile in every patient with locoregionally advanced
      nasopharyngeal carcinoma needs prospective validation, because of the high
      toxicity of this modality.

PMID- 14690001
TI  - The impact of FDG PET on the management of occult primary head and neck tumours.
AB  - AIMS: The aim of this study was to investigate the impact of positron-emission
      tomography (PET) with 18F-labelled fluoro-2-deoxy-D-glucose (FDG) in the
      management of occult primary head and neck tumours. MATERIALS AND METHODS: We
      reviewed 16 patients with squamous cell carcinoma (SCC) and one patient with
      undifferentiated carcinoma of cervical lymph nodes (N1-4; N2a-9; N2b-2; N3-2).
      All patients had full clinical assessment, including examination under
      anaesthesia (EUA), with biopsy of all suspicious areas and random biopsies of
      sites likely to harbour an occult primary site. Nine patients underwent magnetic
      resonance imaging (MRI) of the head and neck, three underwent computed tomography
      (CT) and five underwent both CT and MRI. None of these studies were able to
      locate a primary tumour. Patients received 350 MBq FDG intravenously. Emission
      transmission scans of the extra-cranial head, neck and thorax were obtained using
      an ECAT Exact 47 at least 60 min after injection. The images were interpreted by
      the same radiologist experienced in PET, independent of the final outcome. The
      influence of FDG PET on management was assessed on review of the patients' notes
      after treatment or when treatment had been deemed unnecessary. RESULTS: FDG PET
      suggested a primary site in eight of the 17 patients (tongue base 5; nasopharynx
      1; tonsil 1: supraglottis 1). Pathological confirmation was obtained in four
      patients and one patient died of progressive disease at the primary site. In nine
      patients, the primary site was not identified on FDG PET. In six of these
      patients, no primary site was found during follow-up (range 8-36 months: mean 20
      months). One patient died before treatment commenced, and there were two
      histologically confirmed false-negative FDG PET results: one tonsil SCC and one
      lateral pharyngeal wall SCC. FDG PET affected treatment plans in nine of the 17
      (53%) patients in whom a primary site was suggested (altered radiotherapy plan 6;
      radiotherapy with curative intent to palliative radiotherapy 1; radiotherapy to
      surgery and post-operative radiotherapy 1), and in one patient where no occult
      primary was localised (radiotherapy to surgery 1). FDG PET had a sensitivity,
      specificity, positive and negative predictive value of 62%, 66%, 62% and 62%,
      respectively.

PMID- 14690002
TI  - Efficacy of intra-arterial infusion therapy using a combination of cisplatin and
      docetaxel for recurrent head and neck cancers compared with cisplatin alone.
AB  - AIMS: To compare the initial effect and toxicity, response duration and survival
      time of intra-arterial infusion therapy using a combination of cisplatin (CDDP)
      and docetaxel (DXT) with those using CDDP alone for treatment of recurrent head
      and neck cancers. MATERIALS AND METHODS: Twenty-nine patients with recurrent head
      and neck cancers were treated using intra-arterial infusion chemotherapy. The
      chemotherapeutic regimens consisted of CDDP alone (n=12) or a combination of CDDP
      and DTX (n=17). In the CDDP-DTX group, both CDDP 70 mg/m2 and DTX 60 mg/m2 were
      administrated via the external carotid artery (ECA) or via branches of the ECA or
      subclavian artery. In the CDDP-alone group, CDDP 70 mg/m2 was infused. The tumour
      response (response rate = complete response + partial response) and toxicities
      (World Health Organization [WHO] classification grades 3 and 4) were evaluated in
      both groups and compared by Fisher's exact probability test. RESULTS: The
      response rates in the CDDP-DTX group and the CDDP-alone group were 71% (12/17)
      and 50% (6/12), respectively (P=0.44). Leucocytopenia and neutropenia (grades 3
      and 4) were significantly more prevalent in the former than in the latter group
      (11/17 vs 1/12; 10/17 vs 1/12) (P<0.01). However, there were no infectious
      diseases in any of the patients. CONCLUSION: Combined cisplatin-docetaxel intra
      arterial infusion therapy was shown to be effective and safe for recurrent head
      and neck cancers.

PMID- 14690003
TI  - Radiation induced mucositis: co-ordinating a research agenda.
AB  - AIMS: A one-day workshop was hosted by the Symptom Control Committee of the
      National Cancer Institute of Canada, Clinical Trials Group (NCIC-CTG), in
      conjunction with the October 2002 annual meeting of the Canadian Association of
      Radiation Oncologists in Toronto, Ontario. The primary intention of the workshop
      was to direct the future research agenda of the Symptom Control Committee. Large
      group presentations were held initially to review the contemporary research
      issues of four selected areas of interest: fatigue, brain metastasis, bone
      metastasis and radiation-induced mucositis. Panel members were then charged with
      the identification of specific research proposals that could be considered for
      further development. Research questions were to be clinically relevant and
      currently appropriate. Any additional information needed before the launch of any
      potential trial was also requested. In this paper, we will review and summarise
      the outcomes from the radiation-induced mucositis sessions. MATERIALS AND
      METHODS: Thirty-four participants participated in the large group sessions and
      contributed to one of four panel discussions on selected supportive care issues
      relevant to radiation oncologists. RESULTS: Three potential and non-overlapping
      research questions were identified; two involving mucositis management in
      patients receiving radical radiation for head and neck cancer, and a third for
      patients with advanced lung cancer undergoing combined radiation and chemotherapy
      and at risk for the development of symptomatic oesophagitis. CONCLUSION: The
      workshop successfully identified three potential research questions. The large
      group and the smaller panel discussions successfully established consensus on
      important aspects of future study designs. The current 'standard of care',
      appropriate experimental treatments, primary outcomes of interest and study
      population parameters were each important issues that were discussed. The
      importance of developing meaningful biological assays was reviewed, as was the
      need to ensure the appropriate storage of biological samples from patients for
      future study.

PMID- 14690004
TI  - Neuro-oncology practice in the UK.
AB  - The aim of the study was to determine current U.K. neuro-oncology practice. A
      questionnaire was sent to all U.K. clinical oncologists who treat primary brain
      tumours. Results were distributed to these doctors with an invitation to attend a
      workshop in September 2000 to debate areas of differing practice and to review
      the existing related evidence. A further workshop was held in May 2002. The
      questionnaire responses and discussion of controversial areas, including the
      management of high-grade gliomas, low-grade gliomas, meningiomas, pituitary
      adenomas and multiple-brain metastases are included in this paper.

PMID- 14690005
TI  - The impact of clinical guidelines on surgical management in patients with thyroid
      cancer.
AB  - AIMS: Thyroid cancer is an uncommon but highly curable disease if treated
      optimally. The aim of this study was to determine whether clinical guidelines
      introduced locally at the beginning of 1999 were associated with better surgical
      outcome, using radioiodine uptake as a surrogate measure of completeness of
      thyroidectomy. MATERIALS AND METHODS: We reviewed the medical records of all
      patients with thyroid cancer referred to a cancer centre (n=176) 3 years before
      and 3 years after the introduction of guidelines. The uptake of radioiodine in
      the thyroid bed after thyroidectomy and before radioiodine ablation was used to
      assess the completeness of primary surgical treatment. RESULTS: The number of new
      cases referred to our centre increased from 80 in the 1996-1998 period to 94
      during 1999-2001. This was largely because of an excess of papillary thyroid
      cancers. Documentation in the medical records of the pathological primary tumour
      size improved from 47.5% to 80.8% following the introduction of guidelines. A
      significant reduction in radioiodine uptake in the thyroid bed was observed
      following the introduction of guidelines (5.03% +/- 6.82 (SD) vs 2.75% +/- 5.10
      (SD); P=0.005). Linear regression analysis of clinical variables indicated that
      the year of surgery was the only significant factor influencing radioiodine
      uptake in the thyroid bed (P=0.014). Twelve hospitals within the Northern Cancer
      Network carried out thyroid surgery for thyroid cancer in the pre-guideline era
      compared with seven hospitals in the post-guideline era. Surgeons who were
      members of the regional multidisciplinary thyroid cancer team operated on 35% of
      cases in the 1996-1998 period and 56.4% in the 1999-2001 period (P<0.01).
      CONCLUSIONS: The introduction of clinical guidelines in 1999 was associated with
      a reduction in the size of thyroid remnant after primary surgical treatment. This
      was accompanied by fewer hospitals undertaking thyroid surgery and more patients
      being operated on by surgeons who were members of the thyroid cancer
      multidisciplinary team.

PMID- 14690006
TI  - Spindle epithelial tumour with thymus-like differentiation (SETTLE) of the
      thyroid gland with widespread metastases in a 13-year-old girl.

PMID- 14690007
TI  - A consensus development approach to define national research priorities in bone
      metastases: proceedings from NCIC CTG workshop.
AB  - AIMS: A 1-day workshop was conducted to gather interested Canadian radiation
      oncologists to identify priority research questions that could be answered
      through clinical trials under the auspices of the National Cancer Institute of
      Canada--Clinical Trials Group (NCIC-CTG) Symptom Control committee. MATERIALS AND
      METHODS: In preparation for the workshop, a survey of Canadian radiation
      oncologists resulted in four research areas in symptom control, including
      radiation-induced mucosal reactions, fatigue, radiotherapy for brain metastases
      and radiotherapy for bone metastases. The first half of the workshop consisted of
      plenary sessions where the research setting and perspective was defined for each
      area. This was followed by deliberations by a subgroup of researchers with
      special interest in the topic area. The bone-metastases subgroup deliberated the
      clinical context, the scientific merits and the required methodology of research
      questions related to the role of radiotherapy in early treatment of bone
      metastases, the role of re-irradiation, the role of systemic radiotherapy and
      patient selection for different fractionation schedules. A list of prioritised
      clinical studies was proposed. RESULTS: The question of single vs multi-fraction
      re-irradiation for symptomatic bone metastases was identified as most pertinent
      to the Canadian radiation oncologists present. A multi-centre, international
      intergroup study is undergoing protocol development. Other study concepts, such
      as an alternative dose-schedule of 17 Gy/2 fractions/1 week for intermediate
      prognosis patients, and early referral for radiation oncologist assessment of
      early or mildly symptomatic bone metastases for good-prognosis patients, require
      further methodological development before a clinical trial can be proposed.
      CONCLUSION: An NCIC-CTG workshop provided an update on current evidence-based
      knowledge in palliative radiotherapy for bone metastases. New trial concepts were
      discussed among practitioners and clinical investigators to promote dialogue and
      collaboration. The proposal of an international intergroup randomised trial of
      single vs multiple fraction re-irradiation for painful bone metastases received
      the most support among participants.

PMID- 14690008
TI  - A late relapse of primary Krukenberg tumour with bone metastases.

PMID- 14690009
TI  - Bullous pemphigoid: an unusual and insidious presentation of breast cancer.

PMID- 14690010
TI  - Bilateral retinal detachment as presentation of metastatic mucin secreting
      adenocarcinoma with unknown primary.

PMID- 14690011
TI  - Koebnerized psoriasis masquerading as recurrent breast cancer.

PMID- 14690012
TI  - Changes in plasma lactate and pyruvate concentrations after taking a bath in hot
      deep seawater.
AB  - The use of deep seawater (DSW) in thalassotherapy has begun in Japan. To clarify
      the health effects of DSW on the human body, we investigated the changes in
      plasma lactate and pyruvate concentrations, or subjective judgment scores, after
      bathing at rest in 9 healthy young men. Subjects were immersed for 10 minutes in
      DSW, surface seawater (SSW), and tap water (TW) heated to 42 degrees C. Plasma
      samples were collected before bathing, immediately after bathing, and 60 minutes
      after bathing. The scores were obtained by an oral comprehension test. In the DSW
      bathing, plasma lactate and pyruvate concentrations showed no significant changes
      immediately after bathing or 60 minutes after bathing. In contrast, subjects who
      bathed in SSW showed a significant decrease in lactate concentrations 60 minutes
      after bathing compared with immediately after bathing. Subjects who bathed in TW
      showed a significant increase in lactate concentrations immediately after bathing
      compared with before bathing, and they showed a significant decrease in lactate
      and pyruvate concentrations 60 minutes after bathing. We found no significant
      change in the thermal sensation score in the DSW bathing, though significant
      differences were found between before and immediately after bathing in the SSW
      and TW groups. Moreover, the score decreased significantly 60 minutes after
      bathing compared to immediately after bathing in the TW bathing. Higher
      concentrations of salts contained DSW such as sodium, nitrate-nitrogen, phosphate
      phosphorus, and silicate-silicon may have a good influence on human health.
      Although additional studies are needed to support our findings, DSW is the
      mildest water to the human body among the three kinds of water, since no
      significant changes in the items measured were found only in DSW.

PMID- 14690013
TI  - Partial regeneration/proliferation of the beta-cells in the islets of Langerhans
      by Nigella sativa L. in streptozotocin-induced diabetic rats.
AB  - This experiment was carried out to investigate the effect of N. sativa L. on
      histopathology of pancreatic beta-cells, and blood insulin and glucose
      concentrations in streptozotocin-induced diabetic rats. Fifty male Wistar rats
      (200-250 g) were divided into two experimental groups (diabetics with no
      treatment and diabetics with N. sativa L. treatment), each containing twenty-five
      rats. Diabetes was induced in both groups by a single intraperitoneal injection
      of streptozotocin (STZ) (50 mg/kg). The experimental animals in both groups
      became diabetic within 24 hours after the administration of STZ. The rats in N.
      sativa L.-treated group were given the daily intraperitoneal injection of 0.20
      ml/kg of N. sativa L. volatile oil for 30 days starting the day after STZ
      injection. Control rats received only the same amount of normal saline solution.
      The rats in both groups received the last injection 24 hours before the
      sacrification and 5 randomly-selected rats in each group were sacrificed before,
      and the 1, 10, 20 and 30 days after the STZ injection to collect blood and
      pancreatic tissue samples. The N. sativa L. treatment caused a decrease in the
      elevated serum glucose, an increase in the lowered serum insulin concentrations
      and partial regeneration/ proliferation of pancreatic beta-cells in STZ-induced
      diabetic rats with the elapse of the experiment. It is concluded that the
      hypoglycaemic action of N. sativa L. could be partly due to amelioration in the
      beta-cells of pancreatic islets causing an increase in insulin secretion. More
      studies are needed to demonstrate the exact mechanism of action of N. sativa L.
      on ameliorated blood glucose concentration in STZ-induced diabetes.

PMID- 14690014
TI  - The effect of levamisole combined with the classical treatment in chronic
      brucellosis.
AB  - Levamisole is an immunopotenciator drug which is used as an antihelmintic drug as
      well as very effective remedy on cellular immunity compared with humoral
      immunity. A total 71 patients (37 men, 34 women) who referred to our department
      between March 1997 and December 2001, with a history of the disease for about 1
      year, were diagnosed as having chronic brucellosis through those tests brucella
      serum agglutination test (SAT), SAT with Coombs and SAT with 2-mercaptoethanol.
      The patients were randomly divided into levamisole group (36 patients) and
      control group (35 patients). All patients were given rifampicin 600 mg/day +
      doxycycline 200 mg/day for 6 weeks as a standard classical combined therapy for
      brucellosis. In the levamisole group, oral levamisole 80 mg every other day for 6
      weeks was added to the treatment. There was a statistically significant
      difference between two groups, in complaints of arthralgia, fatigue and sweats
      before and 6 months after treatment, as well as in erythrocyte sedimentation rate
      and C-reactive protein elevations and lymphomonocytosis finding. While it was
      provided both clinical and serological improvement in all patients in the
      levamisole group; 11 patients in the control group did not improve both
      clinically and in view of specific and nonspecific laboratory findings and a
      recurrence occurred in one case, in this group. In conclusion, levamisole added
      to classical antibiotic therapy in treatment of chronic brucellosis was found
      quite efficient in all patients in providing adequate clinical and laboratory
      response in comparison to classical antibiotic therapy alone.

PMID- 14690015
TI  - A novel dysfunctional p53 mutation in the human neuroblastoma cell line TGW.
AB  - Mutations of p53 are rare in primary and advanced neuroblastomas. The p53 gene
      was studied in a TGW cell line established from a TNB1 xenograft, derived from
      metastasized neuroblastoma. The p53 protein level in TGW was elevated at
      baseline. Treatment with doxorubicin to induce genotoxic stress neither altered
      the p53 protein level nor induced p21 protein within 24 hours. DNA sequencing
      analysis revealed a novel triplet deletion mutation at codon 282 (R282del) of the
      p53 gene, a mutation also found in TNB1, indicating that the mutation occurred in
      the relapsed tumor. The mutant was incapable of transactivation and had no effect
      on the transactivational activity of the wild-type p53 gene product in reporter
      assays using a plasmid possessing a p53 responsive element of p21, bax or mdm2.
      These results suggest that the mutant p53R282del found in TGW is a non-functional
      mutant and has no dominant negative nature.

PMID- 14690016
TI  - The role of rho and rho-dependent kinase in serotonin-induced contraction
      observed in bovine middle cerebral artery.
AB  - The current study was designed to characterize the role of Rho and Rho-dependent
      kinase (Rho-kinase) in isometric contractile responses induced by serotonin (5
      HT) and a solution containing 40 mM K(+) (high K(+)) in ring preparations of the
      middle cerebral artery of bovine. Application of W-7, a Ca(2+)-calmodulin
      inhibitor, reversibly and equally attenuated the amplitudes of contractions
      produced by both 5-HT and high K(+). Similar effects were observed with ML-7, an
      inhibitor of myosin light chain kinase. Surprisingly, the protein kinase C
      inhibitors, calphostin C and Ro-31-8220, had no effect on the 5-HT-induced
      contraction. Incubation of preparations with Clostridium difficile toxin A and B
      or with Clostridium botulinum C3 exoenzyme for 48 hours attenuated the 5-HT
      induced response but not the high K(+)-induced response. Application of the Rho
      kinase inhibitor, Y-27632, resulted in marked inhibition of the 5-HT-induced
      response but had negligible effect on the high K(+)-induced response. These
      results suggest that the activation of Rho and Rho-kinase may be involved in the
      generation of the contraction produced by 5-HT in the bovine middle cerebral
      artery, while protein kinase C plays, if any, an insignificant role on the
      contraction.

PMID- 14690017
TI  - Clofibrate, a peroxisome-proliferator, enhances reverse cholesterol transport
      through cytochrome P450 activation and oxysterol generation.
AB  - Fibrates are widely used hypolipidemic agents that activate the peroxisome
      proliferator-activated receptor a (PPARalpha) and regulate the expression of many
      genes involved in lipid metabolism. We studied the mechanism of the effect of
      clofibrate on cholesterol homeostasis. Rats were fed with chow containing
      clofibrate, cytochrome P-450 inhibitor ketoconazole, or clofibrate plus
      ketoconazole. Control rats were fed only with normal chow. The levels of six
      oxysterols in liver microsome were determined. The levels of mRNAs for liver X
      receptor alpha (LXRalpha), ATP-binding cassette A1 (ABCA1), PPARalpha and
      cholesterol 7alpha-hydroxylase (CYP7A) in the liver were analyzed by northern
      blotting. Clofibrate administration decreased plasma levels of total cholesterol
      and triglyceride and increased high-density lipoprotein-cholesterol (HDL-C).
      Clofibrate increased the levels of liver microsomal oxysterols including 25- and
      27-hydroxycholesterol, which are potent activators of LXRalpha. Clofibrate also
      enhanced the expression of mRNAs for PPARalpha, LXRalpha, and ABCA1. Simultaneous
      administration of ketoconazole suppressed the effects of clofibrate on plasma
      lipids, hepatic oxysterol levels, and the expression of the genes. Clofibrate
      increases cytochrome P450 content and the resulting oxysterol generation may
      partly mediate the clofibrate-induced up-regulattion of LXRa and ABCA1, which are
      related to reverse cholesterol transport.

PMID- 14690018
TI  - Clinical relationship of myocardial sympathetic nervous activity to
      cardiovascular functions in chronic heart failure: assessment by myocardial
      scintigraphy with 123I-metaiodobenzylguanidine.
AB  - The aim of this study was to clarify the relationship between cardiac sympathetic
      nervous activity (SNA) assessed by radioiodinated metaiodobenzylguanidine (123I
      MIBG), an analogue of norepinephrine and cardiovascular functions in patients
      with chronic heart failure (CHF). Subjects were 17 patients with CHF. A dose of
      111 MBq of 123I-MIBG was administered intravenously, and 5-minute anterior planar
      images were obtained 15 minutes (early image) and 3 hours (delayed image) after
      the injection. The heart/mediastinum (H/M) count ratio was defined to quantify
      cardiac 123I-MIBG uptake. The washout ratio (WR) of 123I-MIBG from the heart was
      calculated as follows: (early counts-delayed counts)/early counts x 100 (%).
      Echocardiography was performed on all patients within 1 week of 123I-MIBG
      scintigraphy to measure stroke volume index (SVI). Blood pressure and heart rate
      (HR) in the resting state were also recorded to calculate cardiovascular
      functions including cardiac output, pulse pressure (PP), and mean blood pressure.
      Significant linear correlations were found between the early H/M ratio of 123I
      MIBG and SVI, and between the delayed H/M ratio of 123I-MIBG and SVI,
      respectively. WR of 123I-MIBG was correlated with HR, and was inversely
      correlated with SVI and with PP, respectively. It is likely that a decrease in
      SVI is associated with enhanced cardiac SNA in severe CHF. 123I-MIBG scintigraphy
      is effective in assessing the cardiac functional status and SNA in patients with
      CHF in vivo. Moreover, changes in PP and HR indicate well alteration in SNA.

PMID- 14690019
TI  - Relationship between the beta3-adrenoceptor gene variant and body fat in Japanese
      children.
AB  - In this study, we investigated whether the variant of the beta3-adrenoceptor gene
      is associated with accumulation of body fat in Japanese junior high school
      students. A total of 87 junior high school students, 50 boys and 37 girls,
      participated in this survey. The beta3-adrenoceptor gene variant was detected by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
      Accumulation of body fat was assessed by skinfold thickness at the triceps and
      subscapular with a skinfold caliper. There was no difference between boys and
      girls in the frequency of the beta3-adrenoceptor gene allele. There were no
      significant differences in body mass index and percent body fat between the Arg
      carriers (Trp/Arg or Arg/Arg) and the Arg noncarriers (Trp/Trp) for either sex.
      The Trp64Arg variant of the beta3-adrenoceptor gene does not seem to have a
      strong effect on the accumulation of body fat in this group of Japanese junior
      high school students.

PMID- 14690020
TI  - The bony malformations of lumbosacral junction and sacrum: case reports and
      literature review.
AB  - The lumbosacral region, with its manifold variations and anomalies, is one of the
      most important section of the entire spine. From the fusion defects to the
      segmentation anomalies, a wide variety of malformation exists in this region.
      Individuals with such anomalies usually have no physical complaints until their
      spines undergo pathological conditions. Two patients with a variety of
      lumbosacral vertebra anomalies are described. Each of them had a different
      malformation, but low back pain was the common complaint of these patients.
      According to our knowledge, these cases have never been reported before. We
      analysed their clinical and radiological features and discussed with the
      literature.

PMID- 14690021
TI  - Poland's environment--past, present and future state of the environment in the
      Vistula and Odra River basins.
AB  - In the middle of the last century in the case of many river basins, it became
      obvious that the targets of the Helsinki-Commission (HELCOM) concerning a 50%
      reduction of nitrogen and phosphorus inputs to the Baltic Sea had not been
      reached. Such conclusions could be derived from the observed loads. But the
      measurements regarding the analysis were not sufficient to determine what the
      reasons for this report were, what has to be done to fulfil this agreement and to
      evaluate the time at which the targets can be reached. This contribution presents
      the current state of Polish surface water quality as well as results of modelling
      nutrient and heavy metal emissions into the two biggest Polish river basins:
      Vistula and Odra, which both cover approximately 90% of Poland's territory.

PMID- 14690022
TI  - Reconstructed mass-spectrometric pattern for characterization of carbon compounds
      in smoker's lung in situ.
AB  - BACKGROUND: Cigarette smoke is a major anthropogenic pollutant and contributes to
      the permanent load of ambient particulate matter in the air, particularly
      indoors. It is the leading risk factor for premature loss of life due to chronic
      bronchitis, emphysema and lung cancer. Smoker's lung and graphite pneumoconiosis
      are pathological states characterized by the deposition of carbonaceous
      particles. METHODS: Mass spectrometry was used to evaluate unstained lung
      sections obtained in vivo from a heavy smoker and a patient with occupationally
      acquired graphite pneumoconiosis. RESULTS AND DISCUSSION: The composition of
      carbon compounds deposited in lung tissue samples is demonstrated here for the
      first time. Thirty carbonaceous-containing microareas from ten biopsies (three
      areas per biopsy) of lung tissues were analyzed mass-spectrometrically. In each
      case, the samples were taken from a smoker's lung or those demonstrating a
      graphite pneumoconiosis. The lung-tissue samples were selected by light
      microscopy before they were evaporated for mass spectrometry. First-order
      criteria were anionic and cationic mass peaks which occur within the mass
      patterns in lung tissues of smoker's lung, although not in graphite
      pneumoconiosis. Second-order criteria were mass peaks from smoker's lung with
      standard deviations SD < or = 14% of the mean value. First and second-order mass
      peaks matched the mass peaks of experimental cigarette-smoke condensate in 9 out
      of 11 peaks. A software program was developed that enabled fast, automated
      recognition of the typical mass peaks, and thereby confirmed the histological
      diagnosis of smoker's lung. CONCLUSIONS: The analysis of carbonaceous particles
      within lung biopsies from a heavy smoker corresponded to the spectra of tobacco
      condensate and not to the investigated biopsies of graphite peneumoconiosis.
      RECOMMENDATION AND OUTLOOK: The analyses were performed in order to find out
      whether mass-spectrometric criteria exist for the differentiation of carbonaceous
      lung-tissue deposits. Mass spectrometry may be a valuable tool in determining the
      composition of carbon compounds deposited in human lung tissue. So far,
      qualitative assessment of the composition of deposits in lung tissue is only
      possible after the patient is deceased (autopsy).

PMID- 14690023
TI  - A comparative study on the recovery of polycyclic aromatic hydrocarbons from fly
      ash and lignite coal.
AB  - The recovery of polycyclic aromatic hydrocarbons (PAHs) from lignite coal burnt
      in Greek power stations and the fly ash produced is examined comparatively using
      Soxhlet, ultrasonic and accelerated solvent extraction procedures with various
      organic solvents. Soxhlet using toluene/methanol mixture and accelerated solvent
      extraction/toluene were found to be the most efficient methods for fly ash PAHs,
      yielding average recoveries of about 80%. The accelerated solvent
      extraction/toluene procedure was superior for lignite PAHs, yielding 96% average
      recovery, whereas ultrasonic and Soxhlet extraction yielded relatively lower
      recoveries (75% and 67%, respectively).

PMID- 14690024
TI  - Persistence of methyl tertiary butyl ether (MTBE) against metabolism by Danish
      vegetation.
AB  - BACKGROUND: Methyl tertiary butyl ether (MTBE) is the second most highly produced
      industrial chemical in the US and a frequent groundwater pollutant. At the same
      time, MTBE is quite persistent to biotic and abiotic decomposition. The goal of
      this study was to find plant species that could degrade MTBE and might be used in
      phytoremediation. METHODS: Excised roots and leaves (0.3 g) from more than 24
      Danish plant species out of 15 families were kept in glass vessels with 25 ml
      spiked aqueous solution for 2 to 4 days. MTBE concentrations were 1 to 5 mg/L.
      Samples were taken directly from the solution with a needle and injected to a
      purge and trap unit. MTBE and the main metabolite, TBA, were measured by GC/FID.
      RESULTS AND DISCUSSION: Solutions with roots of poplar (Populus robusta) and a
      willow hybrid (Salix viminalis x schwerinii) produced TBA in trace amounts,
      probably stemming from bacteria. Significant MTBE reduction (> 10%) was not
      observed in any of the tests. Leaves from none of the species (trees, grasses and
      herbs) reduced the concentration of MTBE in the solution and no TBA, nor any
      other known metabolite of MTBE, was detected. CONCLUSION: It was not possible to
      find plants capable of efficiently degrading MTBE. This gives rise to the
      conclusion that plants probably cannot degrade MTBE at all, or only very slowly.
      RECOMMENDATIONS AND OUTLOOK: For phytoremediation projects, this has, as
      consequence, that the volatilization by plants (except with genetically
      engineered plants) is the only relevant removal process for MTBE. For risk
      assessment of MTBE, degradation by the plant empire is not a relevant sink
      process.

PMID- 14690025
TI  - Traffic congestion and ozone precursor emissions in Bilbao, Spain.
AB  - GOAL, SCOPE AND BACKGROUND: In urban environments, the measured levels of ozone
      are the result of the interaction between emissions of precursors (mainly VOCs
      and NOx) and meteorological effects. In this work, time series of daily values of
      ozone, measured at three locations in Bilbao (Spain), have been built. Then,
      after removing meteorological effects from them, ozone and traffic data have been
      analyzed jointly. The goal was to identify traffic situations and link them to
      ozone levels in the area of Bilbao. METHODS: To remove meteorological effects
      from the selected ozone time series, the technique developed by Rao and Zurbenko
      was used. This is a widely used technique and, after its application, the
      fraction obtained from a given ozone time series represents an ozone forming
      capability attributable to emissions of precursors. This fraction is devoid of
      any meteorological influence and includes only the apportion of periodicities
      above 1.7 years. In the case of Bilbao, the ozone fractions obtained at three
      locations have been compared on that time scale with traffic data from the area.
      RESULTS AND DISCUSSION: For the 1993-1996 period, a regression analysis of the
      ozone and traffic fractions due to periodicities above 1.7 years (long-term
      fractions), shows that traffic is the main explanatory factor for ozone with R2
      ranging from 0.916 to 0.996 at the three locations studied. Analysis of these
      longterm fractions has made it possible to identify two traffic regimes for the
      whole area, associated to different profiles of ozone forming capability. The
      first one favors low ozone forming capability, and is associated with a situation
      of fluent traffic. The second one shows high ozone forming capability and
      represents congestion. Joint analysis of raw data of ozone and traffic do not
      show any clear pattern due to the strong masking effects that seasonal
      meteorological effects (mainly radiation) have on the measured ozone signal. If
      only immission data of ozone are available, as in this case, a comparison between
      ozone and traffic can only be made on the long-term time scale, since that is the
      only fraction embedded in the ozone time series that can exclusively be
      attributed to emissions of precursors. This fact stresses the need to study the
      different fractions embedded in the time series of ozone measured levels
      separately. CONCLUSION: Though the coefficients obtained in the regression are
      only valid for the 1993-1996 period, these traffic regimes represent long-term
      targets (congestion or fluent traffic) that can inspire policies for a joint
      management of the traffic and pollution by ozone in the area of Bilbao beyond
      that period. RECOMMENDATIONS AND OUTLOOK: The results of this work show the need
      of a joint management of ozone and traffic in Bilbao. Since an accurate knowledge
      of traffic was not available, the use of emission factors to relate traffic and
      actual ozone levels has not been possible. For this reason, this study has
      focused on the long-term fractions of traffic and ozone. In the future, if a more
      accurate knowledge of traffic is available, it will be possible to find
      relationships between traffic and ozone on all time scales.

PMID- 14690026
TI  - The occurrence of disinfection by-products in the drinking water of Athens,
      Greece.
AB  - Application of chlorination for the disinfection of drinking water results in the
      formation of a wide range of organic compounds, called disinfection by-products
      (DBPs), which occur due to the reaction of chlorine with natural organic
      materials. The occurrence of DBPs was studied in samples from four drinking-water
      treatment plants (WTPs) and from the distribution network of Athens, Greece.
      Twenty-four compounds, which belong to different categories of DBPs, were
      monitored, including trihalomethanes (THMs), haloacetic acids (HAAs),
      haloacetonitriles (HANs), haloketones (HAKs), chloral hydrate (CH) and
      chloropicrin (CP). Sampling was performed monthly for a period of two years, from
      three different points at each WTP and from eight points atthe distribution
      network. Samples were analyzed by GC-ECD methods, which included pretreatment
      with liquid-liquid extraction for volatile DBPs and acidic methanol
      esterification for HAAs. The results of the analyses have shown the presence of
      disinfection by-products belonging to all categories studied in all water samples
      collected after prechlorination. The major categories of DBPs detected were THMs
      and HAAs, while the other volatile DBPs occurred at lower concentrations. The
      concentrations of DBPs did not in any case exceed the maximum contaminant levels
      (MCL) set by USEPA and WHO. However, monitoring these compounds needs to be
      continued, because their levels could increase due to changes in the quality of
      water entering the water treatment plants. Reduction of the concentrations of
      DBPs could be achieved by optimization of the chlorination conditions, taking
      into account the effect of time. Moreover, research on alternative disinfection
      methods (e.g. ozone, chlorine dioxide, chloramines) and their by-products should
      be conducted to evaluate their applicability in the case of the drinking water of
      Greece.

PMID- 14690027
TI  - Detection of dioxygenase genes present in various activated sludge.
AB  - GOAL, SCOPE AND BACKGROUND: Activated sludge from refineries contains various
      microorganisms that could utilize aromatics under aerobic conditions due to the
      oxygenase enzymes. Dioxygenase enzymes are oxygenases, which are involved in the
      ring cleavage step of aromatic hydrocarbons. In this study, the selected
      catabolic loci involved in ring cleavage have been monitored in the activated
      sludge samples at different time intervals. The investigation of the dioxygenase
      genes in the Effluent Treatment Plants (ETPs) and evaluation of their presence at
      different time points provides a clue for the aromatic utilizing potential of the
      inherent microbial flora. METHODS: The catabolic gene loci pheB, xylE, tod-isp,
      bed and nahG responsible for the enzymes catechol 1,2-dioxygenase, catechol 2,3
      dioxygenase, toluene dioxygenase-iron-sulphur protein component, benzene
      dioxygenase and naphthalene dioxygenase were used respectively. The time
      dependent change in eubacterial population was demonstrated by the amplification
      of 16S rDNA product, followed by restriction digestion. The template DNA was
      obtained from the activated sludge collected from ETPs. The supporting
      physiological data for the overall performance of sludge was developed using
      respirometric analysis. The on-site COD and MLSS analysis for ETP was used in
      final evaluation. The study was carried out with samples collected from three
      different ETPs and also from a selected ETP at different time intervals. RESULTS
      AND DISCUSSION: The respirometric studies were carried out with phenol, catechol,
      toluene, and naphthalene to arrive at the target genotypes for further study by
      PCR protocol. The respirometric analysis coupled with the COD and MLSS analysis
      represented the physiological capacity of the various sludges. Initially, the
      tracking protocol was optimized by using different sludge samples, which were
      collected from refineries. The selected genotypes were amplified and their
      presence has been confirmed using Southern analysis. The gene loci tod-isp, bed
      and xylE were commonly observed at various time intervals of the sludge from the
      same source. The gene loci pheB and nahG were found to be relatively rare.
      CONCLUSION: The 16S rDNA PCR products after restriction digestion produced
      different DNA fingerprint patterns, suggesting that the microbial community
      composition was diverse in the three sources. Similarly, the presence of the
      catechol 2,3-dioxygenase, benzene dioxygenase and toluene dioxygenase genes
      confirmed the aromatic degrading potential in the various sludges. The probes
      could not pick the nahG and pheB genes. However, the respirometeric assay
      suggested that the oxidative capacity to use naphthalene as a substrate exists.
      RECOMMENDATION AND PERSPECTIVE: Our study of the diversity at various time points
      from the ETP provided an overview of the shifts of the catabolic composition of
      the sludge. This also depends on the influential parameters like the incoming
      pollutant level and the environmental conditions that are prevailing and often
      changing from time to time. The results of direct DNA extraction and PCR
      amplification do reflect the relative abundance of a particular catabolic
      genotype, which could be used to monitor the efficiency of treatment.

PMID- 14690028
TI  - Practical applications of the Fenton reaction to the removal of chlorinated
      aromatic pollutants. Oxidative degradation of 2,4-dichlorophenol.
AB  - BACKGROUND: Chlorophenols (CPs) constitute a group of organic pollutants that are
      introduced into the environment as a result of several man-made activities, such
      as uncontrolled use of pesticides and herbicides, and as byproducts in the paper
      pulp bleaching. Promising removal technologies of chlorinated aromatics consist
      in the application of advanced oxidation processes (AOPs) that can provide an
      almost total degradation of a variety of contaminants. Among these, wide
      application find Fenton systems based on generation of reactive species having a
      high oxidizing power, such as hydroxyl radical HO*. Our objective was that of
      determining the overall degradation efficiency of the model compound 2,4
      dichlorophenol (DCP) by thermal Fenton-type oxidation systems with a view toward
      defining in more details relevant process parameters, the effect of reaction
      temperature and of co-catalyst Cu2+. METHODS: Reaction conditions were similar to
      those generally adopted as optimal in many practical applications, i.e.
      pollutant/Fe2+ (as FeSO4) ratio ca. 20, Fe2+/Cu2+ (co-catalyst) 2:1, pH adjusted
      and controlled at pH 3, and H2O2 in excess (up to four-fold over the
      stoichiometric amount required for complete mineralization). RESULTS AND
      DISCUSSION: The results demonstrate that it is advantageous to carry out the
      reaction at a temperature markedly higher (70 degrees C) than ambient. The
      stepwise addition of H2O2 in aliquots yields an efficient transformation, while
      allowing a convenient control of the reaction exothermicity. Under these
      conditions, the essentially complete removal of the initial DCP is accomplished
      using just one equiv of H2O2 during 15 min; excess H2O2 (5 equivalents) yields
      extensive substrate mineralization. Also relevant, at 70 degrees C dechlorination
      of the initial DCP (and of derived reaction intermediates) is remarkably
      extensive (3-5% residual TOX), already with the addition of 1 equiv of H2O2. At
      the end of the reaction, IC and IC-MS analyses of the solution reveal that only
      low-molecular weight carboxylic acid (acetic, formic, oxalic, malonic, tartaric,
      etc.) contribute to the residual TOC. CONCLUSIONS: The whole of the results
      herein point to the advantage of performing the process at temperatures
      substantially higher than ambient (70 degrees C). Under the conditions adopted,
      almost complete degradation of the initial toxic compound can be achieved using
      hydrogen peroxide in fair excess (e.g., 3.5 equiv H2O2). RECOMMENDATIONS AND
      OUTLOOK: In applying practical Fenton-type degradation systems to heavily
      polluted wastes, either for the pre-treatment of waters with a high COD value
      prior to biodegradation or for complete mineralization of pollutants, the set up
      of appropriate reaction conditions appears to be a key factor. Also, it is
      desirable to keep the concentration of iron salts within the lower limits in
      order to minimize the production and disposal of iron oxide sludges.

PMID- 14690029
TI  - Electrochemical or UV-photochemical oxidation of industrial wastes containing
      polar aromatic sulphonates.
AB  - BACKGROUND AND INTENTION: Aromatic sulphonates other than surfactants and their
      hydroxy and amino-derivatives are important intermediates for the production of
      azo dyes. Their production on a large scale can be detrimental for the
      environment, if the by-products of their synthesis are not disposed of
      appropriately. An industrial waste, the organic components of which were mainly
      amino and hydroxy-substituted aromatic sulphonates, seriously endangers the
      environment close to an dismissed Italian industrial site. Inorganic sulphates
      and chlorides contained in the waste seriously hinder its disposal by
      incineration, since they corrode furnace walls. In this work, preliminary
      exploration of aqueous-phase electrochemically and photochemically induced
      oxidation techniques have been performed as possible alternatives to
      incineration. METHODS: Electrochemically-induced oxidation was experimented on
      individual aromatic sulphonates and on an industrial waste by electrolysing them
      between smooth platinum electrodes at low temperature (5 degrees C) and high
      current densities (0.4 A/cm2) with aqueous 0.5 M NaHSO4 electrolyte.
      Photochemically-induced oxidation was performed by irradiating individual
      aromatic sulphonates or industrial waste with a 500 W mercury lamp in the
      presence of sodium peroxydisulphate. RESULTS AND DISCUSSION: After 200 min
      electrodegradation, 90% of the original compounds disappeared, while 50% Total
      Organic Carbon (TOC) of an industrial waste was removed from solution after 10
      hours. After 180 min UV-photodegradation, 90% of two test aromatic sulphonates
      disappeared, while 65% of TOC of industrial waste was removed after 5 hours.
      CONCLUSIONS: Two methods, electrochemical and UV-persulphate oxidation of an
      industrial waste, were used in order to propose a disposal procedure alternative
      to incineration. Electrodegradation with smooth Pt anode in 0.5 M NaHSO4 at 5
      degrees C halved TOC concentration within 10 hours, while persulphate-assisted UV
      photochemical oxidation with a 500 W high pressure Hg lamp abated two-thirds of
      TOC concentration after 5 hours. Energetic consumption of electrodegradation was
      0.33 kWh/g TOC, while that of photooxidation was larger than 2 kWh/g TOC.
      Although both techniques can be considered efficient from a purely chemical point
      of view, since both are capable of wet-oxidising the aromatic sulphonates and the
      industrial waste, electrodegradation seems more promising than a photochemical
      degradation if economical considerations are also taken into account. Considering
      also that neither cell design nor catalyst were optimised in this preliminary
      study, the energy yield of electrodegradation seems likely to be largely
      improved.

PMID- 14690030
TI  - Control of mercury vapor emissions from combustion flue gas.
AB  - GOAL, SCOPE AND BACKGROUND: Mercury (Hg) emission from combustion flue gas is a
      significant environmental concern due to its toxicity and high volatility. A
      number of the research efforts have been carried out in the past decade
      exploiting mercury emission, monitoring and control from combustion flue gases.
      Most recently, increasing activities are focused on evaluating the behavior of
      mercury in coal combustion systems and developing novel Hg control technologies.
      This is partly due to the new regulatory requirement on mercury emissions from
      coal-fired combustors to be enacted under the U.S. Title III of the 1990 Clean
      Air Act Amendments. The aim of this review work is to better understand the state
      of-the-art technologies of flue gas mercury control and identify the gaps of
      knowledge hence areas for further opportunities in research and development. MAIN
      FEATURES: This paper examines mercury behaviors in combustion systems through a
      comprehensive review of the available literature. About 70 published papers and
      reports were cited and studied. RESULTS AND DISCUSSION: This paper summarizes the
      mechanisms of formation of mercury containing compounds during combustion, its
      speciation and reaction in flue gas, as well as subsequent mobilization in the
      environment. It also provides a review of the current techniques designed for
      real-time, continuous emission monitoring (CEM) for mercury. Most importantly,
      current flue gas mercury control technologies are reviewed while activated carbon
      adsorption, a technology that offers the greatest potential for the control of
      gas-phase mercury emissions, is highlighted. CONCLUSIONS AND RECOMMENDATIONS:
      Although much progress has been achieved in the last decade, techniques developed
      for the monitoring and control of mercury from combustion flue gases are not yet
      mature and gaps in knowledge exist for further advancement. More R&D efforts are
      required for the effective control of Hg emissions and the main focuses are
      identified.

PMID- 14690031
TI  - Water technology for specific water usage.
AB  - BACKGROUND: Water is the basis for life and culture. In addition to the
      availability of water its quality has become a major issue in industrialized
      areas and in developing countries as well. Water usage has to be seen as part of
      the hydrological cycle. As a consequence water management has to be sustainable.
      The aim of the contribution is to give water usage oriented quality criteria and
      to focus on the technical means to achieve them. MAIN FEATURES: Water is used for
      many purposes, ranging from drinking and irrigation to a broad variety of
      technical processes. Most applications need specific hygienic, chemical and/or
      physical properties. RESULTS: To meet these demands separation and reaction
      principles are applied. The reuse of water and the application of water treatment
      with little or no waste and by-product formation is the way to go. Membrane
      separation and advanced oxidation including catalytic reactions are promising
      methods that apply natural processes in sustainable technical performance. Thus
      elimination of specific water constituents (e.g. salts and metals,
      microorganisms) and waste water cleaning (e.g. pollutants, nutrients and organic
      water) can be done efficiently. OUTLOOK: Learning from nature and helping nature
      with appropriate technology is a convincing strategy for sustainable water
      management.

PMID- 14690032
TI  - Professing public health nutrition.

PMID- 14690033
TI  - Out of the box. Nutritional requirements.

PMID- 14690034
TI  - Evaluation of the impact of an iodine supplementation programme on severely
      iodine-deficient schoolchildren with hypothyroidism.
AB  - BACKGROUND: Northern rural areas of Tehran have been shown to have severe iodine
      deficiency in our previous studies. In 1989 the inhabitants of these villages
      received an injection of iodised oil, followed by iodised salt distribution in
      1993. The aim of the present study was to evaluate the effect of the iodine
      supplementation on iodine-deficient schoolchildren with hypothyroidism in these
      villages. METHODS: In total, 571 students aged 6-14 years were studied. Goitre
      was graded according to the World Health Organization classification. Serum
      concentrations of thyroid hormones (thyroxine (T4) and triiodothyronine (T3)) and
      thyroid-stimulating hormone (TSH) were determined using commercial kits, and
      urinary iodine was measured using a digestion method. The results were compared
      with data from our previous study in 1989. RESULTS: Total goitre rate decreased
      by 42% in 1999 compared with that in 1989. A significant decrease in Grade 2
      goitre concomitant with an increase in Grade 1 goitre was seen (P < 0.001).
      Values of the variables studied before (1989) and 10 years after iodine
      supplementation (1999) were: median urinary iodine excretion, 2.0 vs. 19.0 microg
      dl(-1) (P < 0.001); T4, 6.5 +/- 2.0 vs. 8.4 +/- 1.6 microg dl(-1) (P < 0.001);
      T3, 177 +/- 38.0 vs. 145 +/- 29.0 ng dl(-1) (P < 0.001); TSH, 10.8 +/- 15.1 vs.
      1.8 +/- 0.8 microU ml(-1) (P < 0.001). No correlation was found between thyroid
      hormones and TSH on the one hand, and goitre and urinary iodine, on the other.
      Serum T4, T3 and TSH concentrations were within normal ranges in all
      schoolchildren in 1999. CONCLUSION: This study showed that euthyroidism induced
      by administration of iodised oil in iodine-deficient schoolchildren with
      hypothyroidism is sustained following the consumption of iodised salt.

PMID- 14690035
TI  - Impact of the health and living conditions of migrant and non-migrant Senegalese
      adolescent girls on their nutritional status and growth.
AB  - OBJECTIVE: To describe the living conditions of Senegalese adolescent girls
      according to their migration status, and to define the main socio-economic and
      biological determinants of their nutritional and growth status. DESIGN: Health
      and living conditions, sexual maturation, and nutritional and growth status of
      adolescent girls were determined within the framework of a longitudinal study on
      growth. SETTINGS: The capital city of Senegal (Dakar) and a rural community
      (Niakhar), 120 km south-east of Dakar. SUBJECTS: Three hundred and thirty-one
      girls, 14.5-16.6 years of age, were recruited from the same villages. Thirty-six
      per cent of the sample remained in the villages to attend school and/or to help
      with household subsistence tasks (non-migrants). The remaining (64%) migrated to
      cities to work as maids (migrants) and lived in two different socio-economic
      environments: at the home of a guardian during the night and in the house of the
      employer during the daytime. RESULTS: Family rural environment and guardian and
      employer urban environments were socio-economically different (P < 0.001). Living
      conditions in urban areas were better than in rural areas and the employer's
      environment was socio-economically more favourable. Migrants had more advanced
      sexual maturation and higher body mass index (BMI), fat mass index (FMI) and mid
      upper arm circumference than non-migrants. However, migrants were smaller than
      non-migrants. BMI, FMI and weight-for-age were related to socio-economic levels
      and duration of migration. Schooling was positively related to height and
      negatively related to BMI. CONCLUSIONS: Migrants enjoyed better living conditions
      than non-migrants. This could be partly due to the better socio-economic
      environment of the employer. It was associated with earlier puberty and better
      nutritional status, but not with a better growth.

PMID- 14690036
TI  - Why do some overweight children remain overweight, whereas others do not?
AB  - OBJECTIVE: To study the dynamics of childhood overweight and the influence of
      dietary intake on tracking of overweight. DESIGN AND SETTING: A follow-up study
      conducted in China. SUBJECTS: Ninety-five overweight children, 6-13 years old,
      identified from 1455 children at baseline, were followed over a 2-year period.
      METHODS: Data on anthropometry and 3-day dietary intake were collected at
      baseline and during follow-up. Overweight was defined using the International
      Obesity Task Force reference of body mass index (BMI)-for-age. Differences
      between groups were tested using analysis of variance and Cochran-Mantel-Haenszel
      tests. RESULTS: Of the 95 overweight children, 36.8% remained overweight 2 years
      later ('tracking group'). Urban boys were three times more likely than rural boys
      to remain overweight (63.2% vs. 21.9%). At baseline, the tracking group had
      higher BMI, body weight and fat intake (% of energy), and lower carbohydrate
      intake (% of energy), than the non-tracking group (who shifted from overweight to
      not overweight); they were more likely to have a high-fat or high-meat diet, but
      less likely to have a diet high in carbohydrate or vegetables and fruit. During
      the follow-up, the tracking group increased fat intake and reduced carbohydrate
      intake while the non-tracking group did not; and they also grew slower in height
      but faster in weight. Tracking of overweight seemed to be related to tracking of
      high-meat (relative risk (RR) 2.4, 95% confidence interval (CI) 1.0-5.6, P <
      0.05) and high-fat (RR 1.5, 95% CI 0.9-2.5, P < 0.1) diets. CONCLUSION:
      Considerable changes in children's overweight status during childhood and
      adolescence were observed in China, a transitional society. Dietary patterns,
      particularly dietary composition, seemed to influence the tracking patterns of
      overweight.

PMID- 14690037
TI  - Dietary fat intake--food sources and dietary correlates in the Malmo Diet and
      Cancer cohort.
AB  - OBJECTIVES: To identify food sources of fat, to compare food and nutrient intakes
      at different levels of relative fat intake, and to examine the contribution of
      different food groups to the variation in relative fat intake. Relative fat
      intake was expressed as energy contributed by fat in percentage of non-alcohol
      energy. DESIGN: Cross-sectional analysis of baseline data from the Malmo Diet and
      Cancer STUDY: An interview-based diet history method, a structured questionnaire
      and anthropometric measurements were used to obtain data. Analysis of variance
      compared food and nutrient intakes across quintiles of relative fat intake.
      Stepwise regression examined the contribution of food groups to the variation in
      relative fat intake. SETTING: Baseline examinations were conducted between 1991
      and 1996 in the city of Malmo, southern Sweden. SUBJECTS: A sub-sample of 7055
      women and 3240 men of the Malmo Diet and Cancer cohort. RESULTS: The major fat
      sources were dairy products, margarines, meat & meat products, and cakes & buns.
      Most plant foods, especially fruit, vegetables and breakfast cereals, were
      negatively associated with fat intake. Low fat consumers had significantly higher
      intakes of dietary fibre, vitamin C, beta-carotene, folic acid, iron, zinc and
      calcium. Intakes of all types of fatty acids and fat-soluble vitamins were
      positively associated with fat consumption. CONCLUSIONS: The results suggest that
      many food groups and nutrients may confound the associations between relative fat
      intake and disease. Plant foods, especially, are important to consider in studies
      of fat intake and disease risk.

PMID- 14690038
TI  - A comparison between the National Food Survey and the Family Expenditure Survey
      food expenditure data.
AB  - OBJECTIVE: Household budget surveys (HBSs) have been used to assess nutritional
      information for epidemiological purposes. The agreement between this information
      and other comparable data needs to be examined. The aim of this project was to
      compare household food expenditure data between two British HBSs: the National
      Food Survey (NFS) and the Family Expenditure Survey (FES). DESIGN: Household food
      expenditure data were compared between the NFS and the FES for the years from
      1982 to 1993. Differences in expenditure were assessed by year, by household
      composition, by income group and by region; for trends across time for all
      households and for regional, household composition and income group variations.
      SETTING: Great Britain. SUBJECTS: Approximately 88 000 NFS households and 85 000
      FES households surveyed between 1982 and 1993 were used in this analysis.
      RESULTS: Marked differences between the food expenditure data provided by the two
      surveys were observed. Furthermore, differences in time trends were substantial,
      which can lead to different conclusions regarding changes in consumption
      patterns. CONCLUSIONS: There is no obvious reason for the differences in
      household food expenditure between the NFS and the FES. Methodological
      differences between the two surveys cannot provide a full explanation for these
      discrepancies. The NFS and FES are now merged into a single survey (the
      Expenditure and Food Survey). If HBSs are to be used for epidemiological purposes
      their validity needs to be established.

PMID- 14690039
TI  - A Belgian study on the reliability and relative validity of the Health Behaviour
      in School-Aged Children food-frequency questionnaire.
AB  - OBJECTIVE: In the Health Behaviour in School-Aged Children (HBSC) survey, the
      frequency of consumption of a limited number of food items--focusing on fibre,
      calcium and less healthy items--is queried using a 15-item food-frequency
      questionnaire (FFQ). The present study was conducted to assess the reliability
      and relative validity of the HBSC FFQ among school pupils in Belgium. DESIGN AND
      SUBJECTS: To assess the reliability of the FFQ, 207 pupils aged 11-12 years and
      560 pupils aged 13-14 years completed the questionnaire twice, with a test-retest
      interval of 6 to 15 days. To assess the relative validity of the FFQ, in a first
      study data were collected as part of the Flemish HBSC 2000 survey: 7072 pupils
      (11-18 years) completed the FFQ and a 24-hour food behaviour checklist (FBC). In
      a second study, 101 pupils (11-12 years) completed the FFQ and a 7-day food diary
      (FD). RESULTS: Reliability--weighted kappa values between test and retest ranged
      from 0.43 to 0.70, percentage agreement from 37 to 87%, and Spearman correlations
      from 0.52 to 0.82. Relative validity--comparison of the FBC with the percentage
      of respondents who should have consumed the food items on a random day, computed
      from the FFQ, showed good agreement between the FFQ and the FBC for most items.
      Only for cereals, diet soft drinks and other milk products were considerably
      higher food frequencies than expected found from the FBC. Comparison of the FFQ
      with the FD showed overestimation for all but three food items (cheese, soft
      drinks and chips). Spearman correlations ranged between 0.10 for crisps and 0.65
      for semi-skimmed milk. CONCLUSION: The HBSC FFQ is a reliable questionnaire that
      can be used for ranking subjects for most food items, although one must consider
      the overestimation when the FFQ is used for estimating prevalences.

PMID- 14690040
TI  - The relationship between low income and household food expenditure patterns in
      Canada.
AB  - OBJECTIVES: To compare food expenditure patterns between low-income households
      and higher- income households in the Canadian population, and to examine the
      relationship between food expenditure patterns and the presence or absence of
      housing payments among low-income households. DESIGN: Secondary data analysis of
      the 1996 Family Food Expenditure Survey conducted by Statistics Canada. SETTING:
      Sociodemographic data and 1-week food expenditure data for 9793 households were
      analysed. SUBJECTS: Data were collected from a nationally representative sample
      drawn through stratified multistage sampling. Low-income households were
      identified using Statistics Canada's Low Income Measures. RESULTS: Total food
      expenditures, expenditures at stores and expenditures in restaurants were lower
      among low-income households compared with other households. Despite allocating a
      slightly greater proportion of their food dollars to milk products, low-income
      households purchased significantly fewer servings of these foods. They also
      purchased fewer servings of fruits and vegetables than did higher-income
      households. The effect of low income on milk product purchases persisted when the
      sample was stratified by education and expenditure patterns were examined in
      relation to income within strata. Among low-income households, the purchase of
      milk products and meat and alternatives was significantly lower for households
      that had to pay rents or mortgages than for those without housing payments.
      CONCLUSIONS: Our findings indicate that, among Canadian households, access to
      milk products and fruits and vegetables may be constrained in the context of low
      incomes. This study highlights the need for greater attention to the
      affordability of nutritious foods for low-income groups.

PMID- 14690041
TI  - A conceptual framework for intelligence-based public health nutrition workforce
      development.
AB  - OBJECTIVE: This paper describes a conceptual framework and associated
      intelligence requirements for problem-based workforce development for public
      health nutrition. METHODS: A conceptual framework for public health nutrition
      workforce development was constructed based on a review of the literature and
      consideration of the intelligence needs to inform workforce development planning.
      RESULTS: A cyclical conceptual framework including five intelligence-linked
      components including public health nutrition problems and priorities, solutions
      and best buys, work needed, capacity to do the work and workforce development
      needs. This framework applied to the Australian situation illustrates its
      applications in workforce development research and planning. Although the
      existing availability of workforce development intelligence in each of these
      components varies, the framework does provide a systematic approach for workforce
      development research and planning directly related to public health nutrition
      problem resolution. CONCLUSIONS: This framework highlights deficiencies in the
      existing public health nutrition workforce development intelligence and the need
      for further research to inform workforce development strategy planning.

PMID- 14690042
TI  - Public health nutrition workforce composition, core functions, competencies and
      capacity: perspectives of advanced-level practitioners in Australia.
AB  - OBJECTIVES: To investigate the attitudes, experiences and beliefs of advanced
      level public health nutritionists with respect to public health nutrition
      workforce composition, core functions, competency requirements and existing
      workforce capacity. DESIGN: Qualitative study using structured interviews.
      SETTING: Australia. SUBJECTS: Forty-one advanced-level public health
      nutritionists employed in academic and senior technocratic positions in state
      health systems. RESULTS: Advanced-level public health nutritionists recognise the
      diversity of the public health nutrition workforce but clearly identify the need
      for a specialist public health nutrition workforce tier to provide workforce
      leadership. Nominated core functions for public health nutrition reflect broader
      public health core functions but, in the context of nutrition, specific problem
      resolution. Opinions about competency needs were similar to many of the cross
      cutting competencies identified in the public health field but with specific
      application to nutrition problems. Competency in the scientific underpinning of
      nutrition was considered particularly important and delineated this public health
      nutrition workforce from the broader public health workforce. Public health
      nutrition was identified as a specialisation within public health and dietetics.
      Workforce capacity assessments by this group indicate a need for workforce
      development. CONCLUSIONS: Qualitative data from a large proportion of the
      Australian public health nutrition leadership group have identified core
      functions, competencies and workforce development priorities that can be a basis
      for further systematic research and workforce strategy development.

PMID- 14690043
TI  - Definitions for public health nutrition: a developing consensus.
AB  - OBJECTIVES: To assess the level of agreement amongst a panel of public health
      nutrition leaders regarding the key descriptors used to define the field of
      public health nutrition. DESIGN: Cross-sectional survey requiring quantitative
      and qualitative responses representing the first round of a consensus development
      Delphi technique. SETTING: International. SUBJECTS: Expert panel of 24 public
      health nutrition leaders from nine countries in the European Union, the USA and
      Australia. RESULTS: All but one of the panel agreed it was important to have a
      consensus definition for public health nutrition to describe the field
      consistently. Opinion about the length and complexity of this definition tended
      to vary depending on the intended use of the definition. The large majority
      (18/24) supported the inclusion of specific reference to physical activity in a
      definition of public health nutrition, although there was not consensus (> 83%
      agreement as criterion) on this point. Consensus descriptors regarded as
      important in a definition of public health nutrition included: population-based,
      focus on health promotion, food and nutrition systems focus, wellness
      maintenance, primary prevention, applies public health principles, education,
      environmental and political descriptors. Treatment as a descriptor was rated as
      unimportant by a majority (14/24) of panellists, delineating public health
      nutrition from clinical practice. CONCLUSIONS: There is strong international
      agreement amongst public health nutrition leaders in Europe, the USA and
      Australia about a range of descriptors that can be used to define public health
      nutrition. The limitations of using word-for-word definitions between and within
      countries may be overcome by explicit use of the consensus descriptors identified
      in this process.

PMID- 14690044
TI  - Genomics and immunology.

PMID- 14690045
TI  - Serial analysis of gene expression provides new insights into regulatory T cells.
AB  - It is now possible to induce donor-specific transplantation tolerance in adult
      rodents using a number of therapeutic strategies. Such peripheral tolerance is
      maintained by regulatory CD4+ T cells, not only in transplantation models, but
      also in autoimmunity. Differential gene expression analyses have been used to
      identify potential new markers for regulatory T cells, aiming to reveal new
      insights into their mechanisms of action, and to find novel targets for
      therapeutic manipulation of the immune system.

PMID- 14690046
TI  - Membrane proteins with immunoglobulin-like domains--a master superfamily of
      interaction molecules.
AB  - Recent genomic analysis has shown that proteins with immunoglobulin superfamily
      (IgSF) domains are extremely abundant and their number has increased markedly in
      evolution correlating with the development of the adaptive immune system. The
      IgSF domain is particularly good at being recognised and is involved in many
      different kinds of interactions. Thus, analysis of the properties of these
      domains can act as a paradigm for thinking about the roles of newly identified
      gene products. This review summarises the identification, function and properties
      of IgSF domains including, their size, variety of interactions, their strength of
      binding, role of glycosylation and organisation with other proteins.

PMID- 14690047
TI  - Informatics and the immune system: the expanding IL-1 and B7 protein families.
AB  - Remarkable advances in our knowledge of the genome sequence have led to the
      creation of databases that afford the opportunity to discover genes based on the
      presence of specific sequence motifs. The application of this strategy to the
      identification of proteins in families of immunological interest has had a
      visible impact on the sizes of the interleukin 1/18 and the CD28/B7 costimulatory
      molecule families, among many others. This accelerated pace of discovery presents
      a new challenge to match the rate of discovery with biological understanding of
      the functions of these extended protein families.

PMID- 14690048
TI  - Exploring the immunogenome with bioinformatics.
AB  - A better description of the immune system can be afforded if the latest
      developments in bioinformatics are applied to integrate sequence with structure
      and function. Clear guidelines for the upgrade of the bioinformatic capability of
      the immunogenetics laboratory are discussed in the light of more powerful methods
      to detect homology, combined approaches to predict the three dimensional
      properties of a protein and a robust strategy to represent the biological role of
      a gene.

PMID- 14690049
TI  - Quantifying the information in auditory-nerve responses for level discrimination.
AB  - An analytical approach for quantifying the information in auditory-nerve (AN)
      fiber responses for the task of level discrimination is described. A simple
      analytical model for ANT responses is extended to include temporal response
      properties, including the nonlinear-phase effects of the cochlear amplifier. Use
      of simple analytical models for AN discharge patterns allows quantification of
      the contributions of level-dependent aspects of the patterns to level
      discrimination. Specifically, the individual and combined contributions of the
      information contained in discharge rate, synchrony, and relative phase cues are
      explicitly examined for level discrimination of tonal stimuli. It is shown that
      the rate information provided by individual AN fibers is more constrained by
      increases in variance with increases in rate than by saturation. As noted in
      previous studies, there is sufficient average-rate information within a narrow-CF
      region to account for robust behavioral performance over a wide dynamic range;
      however, there is no model based on a simple limitation or use of AN information
      consistent with parametric variations in performance. This issue is explored in
      the current study through analysis of performance based on different aspects of
      AN patterns. For example, we show that performance predicted from use of all rate
      information degrades significantly as level increases above low-medium levels,
      inconsistent with Weber's Law. At low frequencies, synchrony information extends
      the range over which behavioral performance can be explained by 10-15 dB, but
      only at low levels. In contrast to rate and synchrony, nonlinear-phase cues are
      shown to provide robust information at medium and high levels in near-CF fibers
      for low-frequency stimuli. The level dependence of the discharge rate and phase
      properties of AN fibers are influenced by the compressive nonlinearity of the
      inner ear. Evaluating the role of the compressive nonlinearity in level coding is
      important for understanding neural encoding mechanisms and because of its
      association with the cochlear amplifier, which is a fragile aspect of the ear
      believed to be affected in common forms of hearing impairment.

PMID- 14690050
TI  - Neural correlates of an auditory afterimage in primary auditory cortex.
AB  - The Zwicker tone (ZT) is defined as an auditory negative afterimage, perceived
      after the presentation of an appropriate inducer. Typically, a notched noise (NN)
      with a notch width of 1/2 octave induces a ZT with a pitch falling in the
      frequency range of the notch. The aim of the present study was to find potential
      neural correlates of the ZT in the primary auditory cortex of ketamine
      anesthetized cats. Responses of multiunits were recorded simultaneously with two
      8-electrode arrays during 1 s and over 2 s after the presentation of a white
      noise (WN) and three NNs differing by the width of the notch, namely, 1/3 octave
      (NN1), 1/2 octave (NN2), and 2/3 octave (NN3). Both firing rate (FR) and peak
      cross-correlation coefficient (p) were evaluated for time windows of 500 ms. The
      cortical units were grouped according to whether their characteristic frequency
      (CF) was inside ("In" neurons) or outside ("Out" neurons) a 1-octave-wide
      frequency band centered on the notch center frequency. The ratios between the FRs
      and the rhos for each NN and the WN condition and for each group of neurons were
      then statistically evaluated. The ratios of FRs were significantly increased
      during and after the presentation of the NN for the "In" neurons. In contrast,
      the changes for the t" neurons were small and most often insignificant. The
      ratios of the p values differed significantly from 1 in the "In-In" and "In-Out"
      groups during stimulation as well as after it. We also found that the ps of "Out"
      neurons were dependent on the type of NN. Potentially, a combination of increased
      p and increased FR might be a neurophysiological correlate of the ZT.

PMID- 14690051
TI  - Selective expression of beta tubulin isotypes in gerbil vestibular sensory
      epithelia and neurons.
AB  - The seven mammalian isotypes of beta tubulin are strikingly similar in amino acid
      sequence. The differences in isotypic sequence, although small, are nonetheless
      conserved in evolution, which suggests that they may confer distinct functional
      roles. If so, such roles should be reflected in the selective expression of
      isotypes by cell type, or even in the sorting of isotypes to within-cell pools.
      Hair cells of the vestibular sensory epithelia each possess a kinocilium, a
      microtubule-based organelle that could represent a distinct microtubule
      compartment, separate from the extensive microtubule network in the soma. The
      afferent neurons that innervate the vestibular sensory epithelia may also be
      functionally divided into dendritic, somatic, and axonal compartments, each with
      its own complement of microtubules. We have examined the distribution of beta
      tubulin isotypes in gerbil vestibular epithelia using isotype-specific antibodies
      to four isotypes and indirect immunofluorescence. We found that hair cells
      selectively express betaI and betaIV tubulin, while supporting cells express
      betaI, betaII, and betaIV tubulin. However, no sorting of isotypes between
      somatic and kinocilia compartments was found in hair cells. Vestibular ganglion
      cells display three isotypes in the soma, axon, and terminal dendrite
      compartments (betaI, betaII, and betaIII tubulin), but only betaIII tubulin was
      found in calyceal nerve endings. The implication of these findings is that beta
      tubulin isotypes are not sorted to within-cell compartments in hair cells but are
      sorted in some vestibular neurons.

PMID- 14690052
TI  - Lateral wall histopathology and endocochlear potential in the noise-damaged mouse
      cochlea.
AB  - Noise exposure damages the stria and spiral ligament and may contribute to noise
      induced threshold shift by altering the endocochlear potential (EP). The aim of
      this study was to correlate lateral wall histopathology with changes in EP and
      ABR thresholds. CBA/CaJ mice were exposed to octave band (8-16 kHz) noise for 2 h
      at intensities ranging from 94 to 116 dB SPL and evaluated 0 h to 8 weeks
      postexposure. EP in control mice averaged 86 and 101 mV in apical and basal
      turns, respectively. The 94 dB exposures caused a 40 dB temporary threshold shift
      (TTS), and there was with no corresponding change in EP. The 112 and 116 dB
      exposures caused >60 dB threshold shifts at 24 h, and EP was transiently
      decreased, e.g., to 21 and 27 mV in apical and basal turns after 116 dB. By 1
      week postexposure, EP returned to control values in all exposure groups, although
      those exposed to 112 or 116 dB showed large permanent threshold shifts (PTS).
      Cochleas were plastic-embedded and serial-sectioned for light microscopic and
      ultrastructural analysis. Acute changes included degeneration of type II
      fibrocytes of the spiral ligament and strial edema. The strial swelling peaked at
      24 h when significant EP recovery, had taken place, suggesting that these changes
      reflect compensatory volume changes. In the chronic state, massive loss of type
      II fibrocytes and degeneration of strial intermediate and marginal cells was
      observed with drastic reduction in membrane surface area. The results suggest
      that EP shifts do not occur with TTS and also do not add significantly to PTS in
      the steady state. However, EP loss could contribute to acute threshold shifts
      that resolve to a PTS. EP recovery despite significant strial degeneration may be
      partly due to decreased transduction current caused by hair cell damage.

PMID- 14690053
TI  - Age-related changes in cochlear endolymphatic potassium and potential in CD-1 and
      CBA/CaJ mice.
AB  - The CD-1 mouse strain is known to have early onset of hearing loss that is
      progressive with aging. We sought to determine whether a disturbance of K+
      homeostasis and pathological changes in the cochlear lateral wall were involved
      in the age-related hearing loss (AHL) of CD-1 as compared to the CBA/CaJ strain
      which has minimal AHL. In the present study, the endocochlear potential (EP) and
      endolymphatic K+ concentration ([K+]e) were measured in both strains of mice with
      double-barrel microelectrodes at "young" (1-2 mo) and "old" (5-9 mo) ages.
      CBA/CaJ mice displayed no changes with aging in EP and [K+]e of the basal turn.
      In the apical turn, there was a small positive shift of the EP (10 mV) with aging
      under both normoxic and acute anoxic conditions (-EP), without any change of
      [K+]e. Further, there were no obvious pathological changes in the lateral wall of
      CBA/CaJ mice. By contrast, old CD-1 mice displayed a significantly reduced [K+]e
      by 30% in both basal and apical turns with no significant changes in normoxic EP.
      The -EP in the apical turn was significantly reduced in magnitude by 6 mV. A
      severe loss of cells with aging was observed in the region of type IV fibrocytes
      of the apical and basal turns and of type II fibrocytes in the basal turn. A
      complete degeneration of organ of Corti was also observed at the basal turn of
      old CD-1 mice, as well as a basalward decline of spiral ganglion neuron density.
      The pathological changes in spiral ligament of CD-1 mice were similar to those of
      an inbred mouse strain C57BL/6J that expresses an AHL gene (ahl) and might be a
      primary etiology of AHL of CD-1 mice. These findings have ramifications for our
      understanding of AHL and for interpretation of genetic mutations in a CD-1
      background.

PMID- 14690054
TI  - Mechanical noise enhances signal transmission in the bullfrog sacculus.
AB  - Noise has been commonly thought to degrade the performance of sensory systems.
      However, it is now clear that the detection and transmission of weak signals in
      sensory systems can be enhanced by noise via stochastic resonance (SR). In hair
      cells, the quality of mechanoelectrical transduction is enhanced up to twofold by
      nanometer level mechanical noise acting on the hair bundle. We wanted to know
      whether these gains could be preserved, perhaps even enhanced, as information
      flows across hair cell synapses, and into the stream of action potentials that in
      the frog conveys acoustic information to the central nervous system. To approach
      this question, we studied the effects of noise on the signal-to-noise ratio (SNR)
      of the 8th nerve's response to small mechanical stimuli directly applied to the
      amphibian sacculus. We found that approximately 2.5 nm of mechanical noise
      enhanced the response of the saccular nerve up to fourfold, suggesting that the
      positive effects of low-amplitude mechanical noise result in improved
      transmission of acoustic information.

PMID- 14690055
TI  - The aging of the middle ear in 129S6/SvEvTac and CBA/CaJ mice: measurements of
      umbo velocity, hearing function, and the incidence of pathology.
AB  - Measurements of umbo velocity and auditory brainstem response (ABR) were made on
      two different strains of mice, 129S6/SvEvTac (129S6) and CBA/CaJ (CB), within
      three different age ranges. The velocity measurements were made with a laser
      Doppler vibrometer using a semiclosed sound delivery system; the frequency range
      of accurate velocity measurements is from 1 to 21 kHz. The visual detection
      threshold of the ABR was determined at selected frequencies between 2 and 32 kHz.
      The velocity results suggest a small but significant change in umbo velocity with
      age in both strains, between the youngest (1.5-3 months) and mid-aged (12-14
      months) groups. There is also a clear difference in the umbo velocity in the
      youngest animals of the two strains, with the 129S6 having more sensitive middle
      ear function than the CB. These results support the existence of a small age
      related loss in middle-ear sensitivity in the mouse that was first described in
      the BALB/6J strain. The age-related changes in middle-ear function observed in
      both CB and 129S6 are much smaller than the age-related decreases in ABR. Our
      results also describe a statistically significant increase in the incidence of
      middle-ear pathology with age in the 129S6.

PMID- 14690056
TI  - Expression of mucins in mucoid otitis media.
AB  - A hallmark of mucoid otitis media (MOM, i.e., chronic otitis media with mucoid
      effusion) is mucus accumulation in the middle ear cavity, a condition that
      impairs transduction of sounds in the ear and causes hearing loss. The mucin
      identities of mucus and the underlying mechanism for the production of mucins in
      MOM are poorly understood. In this study, we demonstrated that the MUC5B and MUC4
      were major mucins in MOM that formed distinct treelike polymers (mucus strands).
      The MUC5B and MUC4 mRNAs in the middle ear mucosa with MOM were up regulated 5
      fold and 6-fold, compared with the controls. This upregulation was accompanied by
      the extensive proliferation of the MUC5B- and MUC4-producing cells in the middle
      ear epithelium. Further study indicated that the mucin hyperproduction was
      significantly linked to CD4+ and CD8+ T cells and/or CD68+ monocyte macrophages.
      It suggests that MUC5B and MUC4 expression may be regulated by the products of
      these cells.

PMID- 14690057
TI  - Localization and functional studies of pendrin in the mouse inner ear provide
      insight about the etiology of deafness in pendred syndrome.
AB  - Immunolocalization studies of mouse cochlea and vestibular end-organ were
      performed to study the expression pattern of pendrin, the protein encoded by the
      Pendred syndrome gene (PDS), in the inner ear. The protein was restricted to the
      areas composed of specialized epithelial cells thought to play a key role in
      regulating the composition and resorption of endolymph. In the cochlea, pendrin
      was abundant in the apical membrane of cells in the spiral prominence and outer
      sulcus cells (along with their root processes). In the vestibular end-organ,
      pendrin was found in the transitional cells of the cristae ampullaris, utriculi,
      and sacculi as well as in the apical membrane of cells in the endolymphatic sac.
      Pds-knockout (Pds-/-) mice were found to lack pendrin immunoreactivity in all of
      these locations. Histological studies revealed that the stria vascularis in Pds-/
      mice was only two-thirds the thickness seen in wild-type mice, with the strial
      marginal cells showing irregular shapes and sizes. Functional studies were also
      performed to examine the role of pendrin in endolymph homeostasis. Using double
      barreled electrodes placed in both the cochlea and the utricle, the endocochlear
      potential and endolymph potassium concentration were measured in wild-type and
      Pds-/- mice. Consistent with the altered strial morphology, the endocochlear
      potential in Pds-/- mice was near zero and did not change during anoxia. On the
      other hand, the endolymphatic potassium concentration in Pds-/- mice was near
      normal in the cochlea and utricle. Together, these results suggest that pendrin
      serves a key role in the functioning of the basal and/or intermediate cells of
      the stria vascularis to maintain the endocochlear potential, but not in the
      potassium secretory function of the marginal cells.

PMID- 14690058
TI  - Forward masking additivity and auditory compression at low and high frequencies.
AB  - The additivity of nonsimultaneous masking can be used as a measure of
      nonlinearity in the auditory system. For example, two equally effective forward
      maskers should produce 3 dB of additional masking when they are combined,
      assuming linearity with respect to intensity. A combined effect greater than this
      (excess masking) indicates compression. In the present experiments, the signal
      was a 10-ms pure tone presented 20 ms after a 200-ms narrowband noise masker
      and/or immediately after a 20-ms narrow-band noise masker. The signal frequency
      was 250, 500, or 4000 Hz. The signal threshold produced by combining two equally
      effective maskers was measured. At all three frequencies, little excess masking
      was observed for a signal 10 dB above absolute threshold, indicating linear
      additivity (no compression). At signal levels 30 dB above absolute threshold,
      excess masking was observed at all three frequencies. The estimated compression
      exponents were 0.29 at 250 Hz, 0.34 at 500 Hz, and 0.17 at 4000 Hz. In contrast
      with physiological studies on other mammals, the present results provide evidence
      for substantial compression at low frequencies in humans.

PMID- 14690059
TI  - Organ of Corti kinematics.
AB  - The internal workings of the organ of Corti and their relation to basilar
      membrane motion are examined with the aid of a simple kinematic model. It is
      shown that, due to the lever system embodied in the organ of Corti, there is a
      significant transformer gain between basilar membrane and cilia displacements.
      While this transformation is nonlinear, linear response prevails in the narrow
      physiologically relevant operating range of the ciliary transducer. The model
      also simulates cilia deflection when the mechanical stimulus is the length change
      of outer hair cells.

PMID- 14690062
TI  - Update on treatment regimens: prophylaxis versus on-demand therapy.
AB  - Prophylaxis, or the routine scheduled replacement of clotting factor concentrate
      in patients with hemophilia, greatly decreases episodes of joint hemorrhage and
      effectively prevents the development of chronic joint arthropathy and disability.
      Despite clear evidence of its effectiveness and the fact that it is recommended
      by international authorities, prophylaxis still is not widely accepted in the
      hemophilia community. In the United States, approximately half of children with
      severe hemophilia A and one third of those with hemophilia B are on prophylactic
      regimens. Factors limiting acceptance include the need for venous access, factor
      availability, poor acceptance of injection therapy, safety concerns, cost, and a
      perceived lack of need. Questions remaining to be answered include the reasons
      for inter-individual variability in bleeding patterns, predictors for and
      reversibility of joint damage, and the optimal regimen for prophylaxis. A need
      exists for validated and standardized outcome measures in future research, as
      well as for research into factors that affect families' adherence to prophylactic
      regimens for their children.

PMID- 14690060
TI  - ErbB expression: the mouse inner ear and maturation of the mitogenic response to
      heregulin.
AB  - In humans, hair cell loss often leads to hearing and balance impairments. Hair
      cell replacement is vigorous and spontaneous in avians and nonmammalian
      vertebrates. In mammals, in contrast, it occurs at a very low rate, or not at
      all, presumably because of a very low level of supporting cell proliferation
      following injury. Heregulin (HRG), a member of the epidermal growth factor (EGF)
      family of growth factors, is reported to be a potent mitogen for neonatal rat
      vestibular sensory epithelium, but its effects in adults are unknown. We report
      here that HRG-alpha stimulates cell proliferation in organotypic cultures of
      neonatal, but not adult, mouse utricular sensory epithelia. Our findings support
      the idea that the proliferative capabilities of the adult mammalian vestibular
      sensory epithelia differ significantly from that seen in neonatal animals.
      Immunohistochemistry reveals that HRG-binding receptors (erbBs 2-4) and erbB1 are
      widely expressed in vestibular and auditory sensory epithelia in neonatal and
      adult mouse inner ear. The distribution of erbBs in the neonatal and adult mouse
      ear is consistent with the EGF receptor/ligand family regulating diverse cellular
      processes in the inner ear, including cell proliferation and differentiation.

PMID- 14690065
TI  - The promise of third-generation recombinant therapy and gene therapy.
AB  - Recombinant factor VIII and IX products have well-established efficacy and safety
      records. However, concerns about the possibility of viral transmission have
      prompted efforts to develop recombinant products that are free of added human and
      animal proteins. The currently licensed second-generation recombinant factor VIII
      concentrates were introduced in 2000. Two new third-generation products,
      manufactured without any human- or animal-derived materials, are currently in
      development and clinical testing. As an alternative to exogenous factor
      replacement, gene therapy is under investigation for use in the treatment of
      hemophilia. Gene therapy involves the stable insertion of a functional gene for
      long-term expression and secretion of endogenous factor VIII or IX protein.
      Methods used to date have been based on retroviral, adenoviral, and adeno
      associated viral vectors, as well as nonviral electroporation. Three phase I
      trials using these approaches have been completed as of 2002, and one more is
      ongoing. This article reviews the results of recent clinical studies
      investigating third-generation recombinant products and gene-based approaches to
      hemophilia treatment.

PMID- 14690063
TI  - The spectrum of safety: a review of the safety of current hemophilia products.
AB  - The safety of whole blood and blood products has been ensured by several
      different mechanisms introduced over the years, each of which reduces the risk of
      blood-borne infectious diseases. An exhaustive donor selection and screening
      process aims to exclude individuals at risk for infectious disease, and numerous
      screening tests are used to detect infectious pathogens in collected blood.
      During processing, blood is further subjected to various removal or inactivation
      procedures directed against specific pathogens, as well as additional screening
      with nucleic acid testing or polymerase chain reaction (PCR)-based assays.
      Despite these measures, sporadic cases of infection continue to occur, caused by
      both known pathogens and newly emergent ones. Other challenges remain to be met,
      including the detection of infectious blood donated during the seronegative
      window period of infection and the rapid identification of and screening for
      emerging infectious diseases.

PMID- 14690064
TI  - The spectrum of safety: variant Creutzfeldt-Jakob disease in the United Kingdom.
AB  - Beginning in the mid 1980s, an epidemic of bovine spongiform encephalopathy (BSE)
      was seen among cattle in the United Kingdom. The cause was recognized as a prion
      agent transmitted in the meat and bone meal products used as animal feed, a
      practice that was banned in 1988. Unfortunately, by that time, infected cattle
      had already entered the human food supply, and by 1996, several individuals were
      identified with a variant form of Creutzfeldt-Jakob disease (CJD), caused by the
      same infectious agent that had caused the disease in cattle. In the United
      Kingdom, 137 cases of variant CJD have been reported to date. The culprit prion
      protein causes no immune response and contains no nucleic acid, making
      preclinical detection impossible. It is also very resistant to conventional forms
      of inactivation and decontamination. Although no cases of variant CJD have been
      linked to transfusion of infected blood, there is concern that the prion agent
      may be transmissible in blood, and evidence from sheep models suggests that it
      can be. Because it is impossible to detect presymptomatic individuals who carry
      the etiologic prion agent, the United Kingdom has adopted measures to secure the
      safety of its blood supply and to minimize potential routes of infection.

PMID- 14690066
TI  - The epidemiology and definition of the acute respiratory distress syndrome.
AB  - Acute lung injury and ARDS have been clinically recognized syndromes for nearly
      30 years. During that time, the understanding of the risks, pathophysiology, and
      outcomes has changed and improved. The definition for this disease has evolved in
      an attempt to identify more accurately and reliably a more homogeneous patient
      population that could be expected to have similar responses to the disease and
      therapies. The most widely accepted definition is that developed by the AECC in
      1994 and now commonly used in epidemiologic studies and clinical trials.
      Estimates of the incidence of the disease and of mortality are significantly
      affected by variability in definitions used. Current estimates of the incidence
      of ALI, however, range from 3 to 75 cases/100,000 population/year. Mortality
      estimates range from 30% to 40%. Although mortality has improved from more than
      60% 20 years ago, ALI survivors are still faced with an increased risk of death
      as well as significant decrements in physical function and quality of life
      through the first 12 months after hospital discharge. A great deal of progress
      has been made in the understanding and management of ALI patients. Now, as the
      search for new therapeutic options continues, equal attention must be focused on
      studying and improving qualitative outcomes for this group of patients.

PMID- 14690067
TI  - The pathophysiology of acute respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is a heterogeneous process that
      results in diffuse alveolar damage. It is associated with a variety of causative
      factors that can be grouped into two general categories, those associated with
      direct lung injury through the airways and those associated with indirect lung
      injury through the blood stream. Regardless of whether injury originates within
      or outside the lung, a systematic inflammatory response is triggered. This
      article reviews some of the physiologic alterations associated with ARDS before
      focusing on the derangement in the cellular environment.

PMID- 14690069
TI  - Pressure-volume curves in the management of acute respiratory distress syndrome.
AB  - The interpretation of P-V curves is uncertain for several reasons: the influence
      of chest wall compliance, differences in regional lung compliance and
      intrapulmonary gas distribution, lung volume history, lung recruitment beyond the
      LIP, peripheral airway fluid movement, expiratory-flow limitation, differences
      between inflation and deflation limb characteristics, and interobserver
      variability in curve analysis. In addition, many studies of acute lung injury
      have constructed P-V curves following disconnection from the ventilator. The
      inevitable lung volume changes that occur may alter the elastic and viscoelastic
      behavior so that the resulting P-V curve characteristics may not accurately
      reflect conditions during mechanical ventilation. More extensive research seems
      to be required before P-V curves are used as a routine guide for mechanical
      ventilation therapy in ARDS. Furthermore, this article suggests that titrating
      PEEP or VT according to the inflation-limb P-V curve should be done with caution,
      because the mechanical significance of this information is open to question.
      Current research suggests the possibility that PEEP could be targeted according
      to the slope of deflation-limb compliance, because this measure may more
      accurately reflect global alveolar closing pressures. This type of analysis can
      be done only by transferring data into software programs that can perform
      sophisticated curve fitting, and such programs are not readily available to most
      clinicians. From a practical standpoint, there is no compelling clinical evidence
      that adjusting mechanical ventilation according to the P-V curve improves
      mortality or morbidity in ARDS as much or more than can be achieved simply by
      decreasing the VT and Pplat.

PMID- 14690068
TI  - Respiratory system mechanics in acute respiratory distress syndrome.
AB  - Respiratory mechanics research is important to the advancement of ARDS
      management. Twenty-eight years ago, research on the effects of PEEP and VT
      indicated that the lungs of ARDS patients did not behave in a manner consistent
      with homogenously distributed lung injury. Both Suter and colleagues] and Katz
      and colleagues reported that oxygenation continued to improve as PEEP increased
      (suggesting lung recruitment), even though static Crs decreased and dead-space
      ventilation increased (suggesting concurrent lung overdistension). This research
      strongly suggested that without VT reduction, the favorable effects of PEEP on
      lung recruitment are offset by lung overdistension at end-inspiration. The
      implications of these studies were not fully appreciated at that time, in part
      because the concept of ventilator-associated lung injury was in its nascent
      state. Ten years later. Gattinoni and colleagues compared measurements of static
      pressure-volume curves with FRC and CT scans of the chest in ARDS. They found
      that although PEEP recruits collapsed (primarily dorsal) lung segments, it
      simultaneously causes overdistension of non-dependent, inflated lung regions.
      Furthermore, the specific compliance of the aerated, residually healthy lung
      tissue is essentially normal. The main implication of these findings is that
      traditional mechanical ventilation practice was injecting excessive volumes of
      gas into functionally small lungs. Therefore, the emblematic low static Crs
      measured in ARDS reflects not only surface tension phenomena and recruitment of
      collapsed airspaces but also overdistension of the remaining healthy lung. The
      studies reviewed in this article support the concept that lung injury in ARDS is
      heterogeneously distributed, with resulting disparate mechanical stresses, and
      indicate the additional complexity from alterations in chest wall mechanics. Most
      of these studies, however, were published before lung-protective ventilation.
      Therefore, further studies are needed to refine the understanding of the
      mechanical effects of lung-protective ventilation. Although low-VT ventilation is
      becoming a standard of care for ARDS patients, many issues remain unresolved;
      among them are the role of PEEP and recruitment maneuvers in either preventing or
      promoting lung injury and the effects of respiratory rate and graded VT reduction
      on mechanical stress in the lungs. The authors believe that advances in
      mechanical ventilation that may further improve patient outcomes are likely to
      come from more sophisticated monitoring capabilities (ie, the ability to measure
      P1 or perhaps Cslice) than from the creation of new modes of ventilatory support.

PMID- 14690070
TI  - Ventilator-induced lung injury.
AB  - Ventilator-induced lung injury has been established as a significant risk to
      patients receiving PPV. Animal studies have provided definitive experimental data
      that support the existence of VILI. Clinical studies have implied the role of
      VILI in ARDS and ALI patients. In patients who have ARDS or ALI, however, VILI
      cannot be distinguished from exacerbation of the primary condition. Animal and
      clinical studies that clearly show elevated levels of cytokines when PPV is
      applied beyond certain limits support the concept that an inflammatory process is
      activated by PPV. Whether the induction of inflammatory mediators contributes to
      the mortality or morbidity of the ventilated patient has not been established. A
      potential role for anti-inflammatory therapeutic agents is promising. Therefore,
      the following considerations can guide the clinical care of ventilator patients:
      Alveolar pressure exposure (plateau pressure) should be limited to less than 32
      cm H2O. Positive end-expiratory pressure should be applied to avoid end
      expiratory collapse and reopening. Tidal volume should be set at approximately 6
      mL/kg or further guided by plateau pressure limitation. Although studies suggest
      that reducing Ti, flow, and f may be important in avoiding VILI, there are no
      current guidelines. The results of preliminary studies investigating the
      preventative potential of respiratory acidosis, prone positioning, or careful
      vascular pressure management seem promising. Inflammatory response in VILI has
      been established, but a role for intervention, such as general or specific
      suppression of the response, has not been established.

PMID- 14690071
TI  - Lung protective mechanical ventilation in acute respiratory distress syndrome.
AB  - The evidence supports the idea that mechanical ventilation can potentially cause
      further lung injury. The only ventilator manipulation that so far has been shown
      definitively to reduce injury and improve mortality is the reduction of VT to 6
      mL/kg PBW or lower and targeting Pplat to 30 cm H2O or lower. Much research is
      needed to provide further guidance in applying ventilatory support techniques.

PMID- 14690072
TI  - Cleanliness of broilers when they arrive at poultry processing plants.
AB  - An eight-point photographic scale from 1 (very clean) to 8 (very dirty) was used
      to assess the cleanliness of the plumage of 69,783 live broiler chickens
      delivered in 54 loads to three processing plants which were each visited in
      spring, summer and winter. There were considerable variations between the plants
      and between the visits, but most birds were given scores of 6 or 7. The average
      plant scores were 6.07, 6.56 and 6.84, which were associated with frequencies of
      birds with scores of 7 or more of approximately 38, 56 and 73 per cent. There was
      some indication that longer feed-withdrawal times of up to 10 hours were
      associated with dirtier birds.

PMID- 14690075
TI  - Bovine spongiform encephalopathy in Italian herds.

PMID- 14690074
TI  - Mineralised deposits in the uterine glands of mares with chronic endometrial
      degeneration.
AB  - Chronic degenerative disease of the mare's endometrium is characterised by
      changes in the uterine glands, including cystic dilation, hyperplasia and
      periglandular fibrosis. Endometrial biopsies were taken from 23 mares with
      different grades of endometrial degeneration. Solid structures were identified
      within the lumina of the uterine glands and shown to be calcified by
      histochemical staining. Most of them were not homogenous but composed of a
      mixture of mineral and organic substances. Further examinations of these
      mineralised structures by immunohistochemical methods revealed the presence of
      the non-collagenous matrix proteins osteopontin, osteonectin and bone
      sialoprotein, which are known to be involved in calcification processes such as
      urolithiosis. Osteopontin and bone sialoprotein were identified within the
      calculi, frequently arranged in concentric layers. Osteonectin was the only
      matrix protein that was also present in the glandular epithelium. Osteocalcin was
      not found in either the calculi or the glandular epithelial cells.

PMID- 14690073
TI  - Purulent rhinitis and otitis caused by Pseudomonas aeruginosa in sheep showered
      with contaminated 'shower wash'.
AB  - Three crossbred lowland ewes developed a severe purulent rhinitis and another
      three ewes developed a severe purulent otitis externa/media after being showered
      with a wash that had been used 24 to 48 hours before on a separate group of
      Cheviot ewes with lesions of dermatitis. Pseudomonas aeruginosa was isolated in
      pure growth from the aural and nasal abscesses and also from the dermatitis
      lesions. Extended antibiotic susceptibility testing and the random amplification
      of polymorphic DNA indicated that a single clonal type was associated with the
      rhinitis and otitis and with the dermatitis, providing strong evidence of an
      epidemiological link between the lesions of dermatitis and the aural and nasal
      abscesses through the use of the contaminated 'shower wash'.

PMID- 14690076
TI  - Use of in vivo-recovered oocytes and adult somatic cells from the same donor for
      nuclear transfer in cattle.

PMID- 14690077
TI  - Disseminated ciliated protozoan infection in a Pacific dolphin (Tursiops gilli).

PMID- 14690078
TI  - Cheilospirura species (gizzard worm) infection in battery-caged commercial layer
      chickens.

PMID- 14690079
TI  - Priapism in a semiwild Asian elephant (Elephas maximus) in Vietnam.

PMID- 14690080
TI  - Doramectin toxicity in a collie.

PMID- 14690081
TI  - Continuing anxiety about BSE.

PMID- 14690082
TI  - Use of Immobilon in deer.

PMID- 14690083
TI  - Voluntary scrapie flocks scheme.

PMID- 14690084
TI  - Increased mortality on a free-range layer site.

PMID- 14690085
TI  - Top-up fees and university funding.

PMID- 14690086
TI  - Veterinary pathology.

PMID- 14690087
TI  - Lamb and kid mortality in village flocks in the coastal savanna zone of Ghana.
AB  - A cohort study was designed to observe and follow up mortality in lambs and kids
      in 88 flocks of sheep and goats under the traditional production system in five
      villages within the coastal savanna zone of Ghana over a 2-year period. The
      overall mortality rates for kids and lambs were 30.8% and 33.5%, respectively.
      Significantly higher proportions of kids (80.2%) and lambs (75.6%) up to 3 months
      of age died compared to kids and lambs from 4 to 12 months of age. The
      differences in mortality rates, either between male and female kids and lambs or
      between single-born and multiple-birth kids and lambs, were not significant. The
      odds ratio (OR) and relative risks (RR) for lambs and kids, on the basis of sex
      and birth types, were not significant; neither were the values obtained for
      attributable risk, attributable fraction, population attributable risk and
      population attributable fraction. The overall mortality rate on the basis of
      species of animal was not significant. At the village level, significant
      differences in the proportions of mortality on the basis of sex were seen in two
      villages. At Akotokyir, more male lambs (54.2%) died compared to females (27.6%),
      while at Apewosika more female lambs (42.2%) died compared to males (16.7%). The
      only significant difference in mortality proportions on the basis of birth type
      at the village level was seen at Apewosika, where more single-born kids died
      (52.8%) compared to kids born with sibling(s) (28.4%). The significant ORs for
      mortalities were 3.10 for male lambs at Akotokyir, 3.35 for female lambs at
      Apewosika and 2.82 for single-born kids at Apewosika. The corresponding RRs were
      equally significant. On the basis of species, significantly more lambs died at
      Akotokyir (44.2%) and Kwesimprah (44.7%) compared to kids. The implications of
      these findings are discussed.

PMID- 14690088
TI  - Foot and mouth disease and livestock husbandry practices in the Adamawa Province
      of Cameroon.
AB  - Foot and mouth disease (FMD) is a highly contagious viral disease of even-toed
      ungulates and is endemic in most of the tropics. A cross-sectional study using a
      stratified, two-stage random sample design was undertaken in the Adamawa Province
      of Cameroon. The objectives were to measure the reported herd-level prevalence of
      FMD and a range of husbandry practices important for its transmission. The owner
      reported prevalence for the previous 12 months was 57.9% (50.4-65.4%), although
      there was a significant variation across the Province. During the previous dry
      season, 46.5% (38.6-54.4%) of herds had gone on transhumance. Herds had high
      numbers of contacts with other herds while on transhumance (98.6%), at pasture
      (95.8%) and at night (74.4%), with medians of 7-10, 4-6 and 1-3 daily contacts,
      respectively. The high level of endemic FMD and potential for disease spread
      presents a significant challenge for control and eradication. Locally sustainable
      methods need to be developed upon which larger regional control programmes could
      be built in the future.

PMID- 14690089
TI  - Immunization of crossbred cattle (Bos indicus x Bos taurus) with fractionated
      midgut antigens against Hyalomma anatolicum anatolicum.
AB  - Crossbred calves (Bos indicus x Bos taurus) were immunized with a fractionated
      midgut supernate antigen (GS-F Ag from Hyalomma anatolicum anatolicum). The first
      inoculation on day 0 was given intramuscularly after emulsification with Freund's
      complete adjuvant; the second was given subcutaneously on day 14 in incomplete
      Freund's adjuvant; and the third on day 35 was given subcutaneously without
      adjuvant. Each injection comprised 1 mg of antigen protein. Ten days after the
      last inoculation, the immunized calves were challenged simultaneously with 1000
      larvae and 20 pairs (20 males and 20 females) of adult H. a. anatolicum on one
      ear and a similar number of Hyalomma dromedarii ticks on the other ear. There was
      a significant decrease in the percentage larval engorgement and larval rejection
      of up to 34% on the immunized calves. A significant increase in the engorgement
      and preoviposition periods and a significant decrease in the engorged weight, egg
      mass weight and reproductive index were observed for adult female ticks when fed
      on the immunized calves. The GS-F Ag also induced a considerable degree of cross
      protection in calves against H. dromedarii larval ticks.

PMID- 14690091
TI  - Abnormalities of the testes and epididymis in bucks and rams slaughtered at Debre
      Zeit abattoir, Ethiopia.
AB  - A study was conducted at Debre Zeit export abattoir on 404 bucks belonging to
      four breeds and 167 rams of two breeds. The animals were selected from the
      slaughter flock using stratified sampling based on breed. Ante-mortem and post
      mortem examinations were carried out after each animal was carefully identified.
      Various genital abnormalities were observed, among which testicular atrophy and
      epididymitis were the predominant genital problems in both bucks and rams. The
      prevalence of cryptorchidism was higher (p<0.05) in bucks than in rams, while
      epididymitis (p<0.05), sperm granuloma (p<0.01) and epididymal cysts (p<0.05)
      were more frequent in rams. In bucks, none of these abnormalities was
      significantly associated with age (p>0.05). However, testicular atrophy (p<0.01),
      epididymitis (p<0.01) and haemorrhagic lesions (p<0.05) were associated with
      breed, the prevalence being higher in Woito-Guji and Boran bucks than in the Arsi
      Bale and Afar breeds. In rams, age affected (p<0.05) the incidence of testicular
      atrophy, epididymitis and sperm granulomas. Epididymitis, sperm granuloma and
      epididymal cysts were more frequent (p<0.01) in Adal rams than in Black Head
      Somalis.

PMID- 14690090
TI  - Studies on the epidemiology of tropical theileriosis (Theileria annulata
      infection) in cattle in Central Anatolia, Turkey.
AB  - An epidemiological survey for Theileria annulata infection was conducted in 12
      selected villages around Ankara in Central Anatolia, Turkey, during the period
      April 1990 to January 1993. During the survey, 198 cattle of 30 local breeds, 84
      Holstein-Friesian x local breeds and 84 Holstein-Friesian breed were examined for
      antibodies to T. annulata and the presence of the vector ticks. Four species of
      Hyalomma ticks were identified: Hyalomma anatolicum anatolicum, Hyalomma
      anatolicum excavtum, Hyalomma detritum and Hyalomma marginatum marginatum.
      Salivary gland staining indicated that infected adult ticks of all four species
      were present and, therefore, were implicated in the transmission of tropical
      theileriosis in the field. Generally, the Hyalomma infestation rate was low, with
      the heaviest infestations occurring on the older animals. Young adults and calves
      had very low infestation rates. Most ticks seen on cattle were adults, very few
      nymphs were found. The blood smear and serological examination of the 198 cattle
      conducted in March, before the start of the first disease season, showed that the
      prevalence of piroplasmosis was 11.1% (22 out of 198) and the seroprevalence of
      T. annulata was 10.6% (21 out of 198). Forty-three animals were then excluded
      from the study because they were seropositive and/or harboured piroplasms. Ninety
      two seronegative animals showed piroplasmosis (92 out of 155) and 34 seronegative
      animals became seropositive for T. annulata (34 out of 155) during the three
      disease seasons. One animal became clinically ill with tropical theileriosis and
      required treatment. The incidence of cattle showing piroplasmosis and disease in
      the total study sample was 50.7% and 0.5% per disease season, respectively. The
      seroconversion rate of new infection with T. annulata in the total study was
      14.3% per animal season. The number of cattle showing piroplasmosis was much
      greater than the number of seropositive cattle, which may indicate the presence
      of another species of Theileria. The two different management systems encountered
      in the study were considered to have influenced the tick infestation levels.

PMID- 14690092
TI  - Reproductive performance of crossbred dairy cows in different production systems
      in the Central Highlands of Ethiopia.
AB  - The study was conducted to examine the fertility status of crossbred dairy cows
      in mixed crop-livestock production (MCLP), market-oriented specialized dairy
      production (MSDP) and urban dairy production (UDP) systems, including the Holetta
      Agricultural Research Center (HARC). Data on general farm management variables
      and reproductive histories were collected from study farms by questionnaire and
      from individual cow records. Age at first service and age at first calving were
      29.58 months (n = 424) and 40.6 months (n = 348), respectively. Cows managed
      under UDP were younger at first service and at first calving (p<0.05). The mean
      intervals from calving to first service and to conception were 141.98 days (n =
      284) and 185.02 days (n = 219), respectively. The mean calving interval for cows
      was 551.82 days (n = 258). Cows in MCLP had longer intervals from calving to
      first service and to conception and longer calving intervals than those managed
      under MSDP, UDP and HARC. First service conception rate (43.42%), number of
      services per conception (1.75) and pregnancy rate (79.29%) did not differ
      significantly between production systems. Reproductive performance was best in
      UDP followed by HARC and MSDP. The difference between MCLP and the rest points to
      particular difficulties in that system. To improve reproductive performance and
      economic benefit, there should be conservative stocking rate, sensible year-round
      feeding, a herd health plan, and sustainable extension service.

PMID- 14690093
TI  - Comparative analysis of village chicken production in two farming systems in
      Burkina Faso.
AB  - This study aimed to describe and compare village chicken production in two
      farming systems in Burkina Faso. The systems were those in which crops and
      livestock production were, respectively, the most important. A rapid rural
      appraisal preceded a monitoring study in which data were collected fortnightly
      for 2 months. The study revealed that village chickens are used as sacrifices,
      gifts and objects of exchange for traditional medicine, or are sold for a little
      money under both systems. Chicken production is a free-range procedure in both
      farming systems, but there are differences in management. On average, the flock
      size was 33.5 +/- 3 birds, of which 57% were chicks. During the period of 2
      months in the rainy season, the overall mortality was relatively low (8.8% +/-
      1.5) but mortality in chicks was high (31.7%). The main cause of financial loss
      in the village chickens was mortality, which represented up to 84% of the total
      exits. The hatching rate and mortality in young chicks differed significantly (p
      < 0.05) between the two farming systems.

PMID- 14690094
TI  - The efficacy of nicorandil, calcium chloride and nitroglycerin in treatment of
      ropivacaine-induced cardiotoxicity.
AB  - BACKGROUND AND OBJECTIVE: The amide-linked local anaesthetics, bupivacaine and
      ropivacaine, can cause depression of cardiac contractility and dysrhythmias. In a
      previous study, we observed decreased contractility and ST segment depression
      following ropivacaine administration in anaesthetized dogs. The efficacy of
      intravenous (i.v.) and intracoronary nicorandil (30 and 100 microg kg(-1)), i.v.
      nitroglycerin (glyceryl trinitrate) (5 microg kg(-1)) and calcium chloride (1, 2
      and 4 mmol) in reversing the cardiotoxic effects of intracoronary ropivacaine
      were studied following the administration of intracoronary ropivacaine. METHODS:
      Six dogs were studied. The dogs were anaesthetized with i.v. pentobarbital (30 mg
      kg(-1)). A left-sided thoracotomy was performed and the left circumflex coronary
      was cannulated. For each dog, the dose of ropivacaine was identified, which
      produced measurable cardiotoxicity. In each case, ropivacaine was followed by one
      of the three resuscitation drugs. The effects of each resuscitation drug on ST
      segments and left ventricular contractility (dP/dt) produced by ropivacaine alone
      were compared with those produced by ropivacaine followed by each of the three
      resuscitation drugs using Fisher's exact test. RESULTS: The doses of ropivacaine
      required to produce depression of left ventricular dP/dt and ST segments ranged
      from 1 to 8 mg. Ropivacaine-induced depression of left ventricular contractility
      (dP/dt) was more rapidly and completely reversed by calcium chloride than by
      either nitroglycerin or nicorandil (P = 0.008). CONCLUSIONS: Calcium chloride may
      be effective in the treatment of inadvertent intravascular administration of
      amide local anaesthetic agents.

PMID- 14690095
TI  - Desflurane increases heart rate independent of sympathetic activity in dogs.
AB  - BACKGROUND AND OBJECTIVE: Desflurane has been shown to increase sympathetic
      activity and heart rate (HR) in a concentration-dependent manner. Nevertheless,
      desflurane, like all other volatile anaesthetics, increased HR in parallel to
      vagal inhibition in a previous study. Therefore, our hypothesis is that
      desflurane elicits tachycardia by vagal inhibition rather than by activation of
      the sympathetic nervous system. METHODS: Six dogs were studied awake and during
      desflurane anaesthesia (1 and 2 MAC) alone, after pretreatment with propranolol
      (2 mg kg(-1) followed by 1 mg kg(-1) h(-1)), or after pre-treatment with atropine
      (0.1 mg kg(-1) followed by 0.05 mg kg(-1) h(-1)). The effects on HR and HR
      variability were compared by an analysis of variance (P < 0.05). HR variability
      was analysed in the frequency domain as power in the high-(0.15-0.5 Hz, vagal
      activity) and low-frequency range (0.04-0.15 Hz, sympathetic and vagal activity).
      RESULTS: HR increased during 2 MAC of desflurane from about 60 (awake) to 118 +/-
      2 beats min(-1) (mean +/- SEM) in controls and to 106 +/- 3 beats min(-1) in dogs
      pre-treated with propranolol. In contrast, pretreatment with atropine increased
      HR from 64 +/- 2 to 147 +/- 5 beats min(-1) (awake) and HR decreased to 120 +/- 5
      beats min(-1) after adding desflurane. High-frequency power correlated inversely
      with HR (r2 = 0.95/0.93) during desflurane alone and in the presence of beta
      adrenoceptor blockade, with no significant difference between regression lines.
      There was no correlation between these variables during atropine/desflurane.
      CONCLUSIONS: The increase in HR elicited by desflurane mainly results from vagal
      inhibition and not from sympathetic activation.

PMID- 14690096
TI  - Intraoperative catecholamine release in brain-dead organ donors is not suppressed
      by administration of fentanyl.
AB  - BACKGROUND AND OBJECTIVE: Endogenous catecholamines are released in brain-dead
      organ donors following painful stimulation during retrieval surgery, and might be
      harmful to harvested organs. Our hypothesis was that inhibition of pain by
      fentanyl would inhibit such catecholamine release. METHODS: We tested 17 brain
      dead organ donors in a randomized, placebo-controlled, double-blinded study.
      Blood samples for determination of epinephrine and norepinephrine concentrations
      were obtained before and 10 min after in take of either fentanyl 7 microg kg(-1)
      or an equivalent volume of placebo. Further points of measurement were taken
      after skin incision and sternotomy. Mean arterial pressure and heart rate at
      these points were recorded. RESULTS: Catecholamine concentrations rose following
      painful stimuli. No differences in haemodynamics, between the fentanyl and the
      placebo group were detectable. Epinephrine concentrations, but not those of
      norepinephrine, were higher in the fentanyl group, reaching significance
      following sternotomy. CONCLUSION: We conclude that the use of fentanyl (7 microg
      kg(-1)) was not effective in suppressing the catecholamine release, following
      painful surgical stimulation in brain-dead organ donors.

PMID- 14690097
TI  - Inflammation increases sufentanil requirements during surgery for inflammatory
      bowel diseases.
AB  - BACKGROUND AND OBJECTIVE: Inflammation promotes hyperalgesia and increases opioid
      binding protein (alpha1-acid glycoprotein) inducing increased opioid requirement.
      To investigate the influence of an acute episode of inflammatory bowel disease in
      opioid requirement during major abdominal surgery, 17 patients with Crohn's
      disease, 12 patients with ulcerative colitis and seven patients without any
      inflammatory process (control group) were prospectively studied. Sufentanil
      requirements were assessed during surgery. METHODS: Sufentanil administration was
      adjusted when haemodynamic variables changed more than 20% of preoperative
      values. In a subgroup of 20 patients (Crohn's disease: 7, ulcerative colitis: 7,
      control group: 6), plasma concentrations of alpha1-acid glycoprotein and unbound
      sufentanil were measured. Total plasma clearance of sufentanil was also
      determined. Data presented as median (25-75 per thousand) were analysed by non
      parametric and ANOVA tests. RESULTS: Despite similar surgery duration,
      intraoperative sufentanil requirements were significantly larger in both the
      Crohn's disease group (0.9 (0.6-1.6) microg kg(-1) h(-1)) and the ulcerative
      colitis group (1.1 (0.6-1.7) microg kg(-1) h(-1)) than in the control group (0.5
      (0.4-0.5) microg kg(-1) h(-1)). Total plasma clearance of sufentanil was larger
      in patients with inflammatory bowel disease than in the control group. The plasma
      alpha1-acid glycoprotein concentration was increased in the inflammatory bowel
      disease group. However, the free fraction of sufentanil was similar in all three
      groups. The largest sufentanil consumption in patients with inflammatory bowel
      disease was observed during time of pain stimulation in the area of referred
      hyperalgesia from the affected viscus. In the control group, the sufentanil
      requirement was constant throughout surgery. CONCLUSION: Inflammatory bowel
      disease increases opioid requirement during major abdominal surgery.

PMID- 14690098
TI  - COX 2 selectivity of non-steroidal anti-inflammatory drugs and perioperative
      blood loss in hip surgery. A randomized comparison of indomethacin and meloxicam.
AB  - BACKGROUND: In this prospective randomized study we tested the hypothesis that
      use of more cyclo-oxygenase 2 (COX 2)-selective non-steroidal anti-inflammatory
      drugs (NSAIDs) can reduce perioperative blood loss compared with non-selective
      NSAIDs. METHODS: Data from 200 patients who underwent total hip replacement were
      studied. Two NSAIDs were compared: indomethacin 50 mg (n = 82) and meloxicam 15
      mg (n = 86). Both NSAIDs were given orally 1 h before surgery. RESULTS: The two
      groups were not different with respect to age, gender, ASA class or duration of
      surgery. When indomethacin was used preoperatively, intraoperative blood loss was
      623 +/- 243 mL (mean +/- SD) and postoperative blood loss 410 +/- 340 mL. After
      meloxicam, these values were 524 +/- 304 mL and 358 +/- 272 mL, respectively.
      Total perioperative blood loss after meloxicam was 17% (P < 0.05) less than that
      observed after indomethacin. CONCLUSION: Perioperative blood loss after meloxicam
      is less than after indomethacin. These in vivo findings are consistent with in
      vitro results using selective COX 2 NSAIDs.

PMID- 14690099
TI  - User acceptance of an anaesthesia information management system.
AB  - BACKGROUND AND OBJECTIVE: This paper describes the user acceptance of an
      anaesthesia information management system at the University Hospital in Giessen,
      Germany, after 5 yr of routine use. METHODS: A questionnaire with 75 items was
      distributed to all anaesthesiologists and anaesthetic nurses of the Department of
      Anaesthesiology. The questions were answered anonymously on a five-point Likert
      scale. RESULTS: The return rate was 60% (44 physicians and 24 nurses). The
      results indicated that the system generally met user expectations. The
      respondents thought that electronic record keeping improved the quality of their
      work, and they did not want to switch back to paper records. Problems arose with
      hardware placement and software features, e.g. coding tools for diagnoses and
      type of surgery. The perceived quality of training strongly influenced user
      acceptance. CONCLUSIONS: Despite the deficits revealed by the survey, the
      respondents did not want to switch back to manual record keeping. A structured
      user survey is a useful tool for the development, adaptation and implementation
      of an anaesthesia information management system. A training strategy that takes
      the needs of the users into account is recommended.

PMID- 14690101
TI  - A prospective, randomized, double-blind comparison of epidural levobupivacaine
      0.5% with epidural ropivacaine 0.75% for lower limb procedures.
AB  - BACKGROUND AND OBJECTIVE: This prospective, randomized, observer-blinded study
      compared onset time and duration of epidural anaesthesia produced by with
      levobupivacaine and ropivacaine for lower limb surgery. METHODS: ASA I-III adult
      patients undergoing elective lower limb procedures were randomized to receive
      epidural levobupivacaine 0.5% 15 mL (n = 30) or epidural ropivacaine 0.75% 15 mL
      (n = 35). A blinded observer evaluated onset time and regression of motor and
      sensory block, and intraoperative needs for fentanyl supplementation (0.1 mg
      intravenously). RESULTS: With levobupivacaine, onset time was 29 +/- 24 min, with
      ropivacaine it was 25 +/- 22 min (P = 0.41). Complete resolution of motor block
      required 105 +/- 63 min with levobupivacaine and 95 +/- 48 min with ropivacaine
      (P = 0.86). The time for regression of sensory block to T12 was 185 +/- 77 min
      with levobupivacaine and 201 +/- 75 min with ropivacaine (P = 0.46). Analgesic
      supplementation was required in one patient receiving levobupivacaine (3.5%) and
      in two patients receiving ropivacaine (5.7%) (P = 0.99). CONCLUSIONS: In adults
      undergoing lower limb surgery, levobupivacaine 0.5% 15 mL produces an epidural
      block with the same clinical profile as ropivacaine 0.75% 15 mL.

PMID- 14690100
TI  - Sub-Tenon's block reduces both intraoperative and postoperative analgesia
      requirement in vitreo-retinal surgery under general anaesthesia.
AB  - BACKGROUND AND OBJECTIVE: We compared the effects of sub-Tenon's local
      anaesthetic block and placebo on peri-operative opioid requirement and
      cardiovascular stability and on postoperative pain, nausea and vomiting in
      patients undergoing vitreo-retinal surgery under general anaesthesia. METHODS: We
      studied 43 patients undergoing vitreo-retinal surgery under general anaesthesia
      in a randomized double blind study. Patients received a standard general
      anaesthetic followed by a sub-Tenon's injection of 4-5 mL of either bupivacaine
      0.75% or saline. We recorded intraoperative invasive arterial pressure, then the
      incidence and severity of pain and of nausea and vomiting, for 24 h
      postoperatively. RESULTS: In the sub-Tenon's bupivacaine group, there was a
      significant reduction in the perioperative opioid use and a reduction in the
      frequency of bradycardia and hypertensive episodes, defined as a rise > 25% of
      baseline for a duration of > 3 min. The sub-Tenon's bupivacaine group also had
      significantly lower pain scores and nausea scores at 12 h, concomitant with a
      lower consumption of analgesia and antiemetics. CONCLUSIONS: This local
      anaesthetic technique is effective in vitreo-retinal surgery and can be safely
      applied to this population of patients regardless of axial length.

PMID- 14690102
TI  - Analgesic effects of intrathecal neostigmine.

PMID- 14690103
TI  - Central venous catheter malposition in an anomalous pulmonary vein.

PMID- 14690104
TI  - A double-lumen tube technique for selective lobar isolation.

PMID- 14690105
TI  - Life-threatening airway obstruction caused by cervical osteophytes.

PMID- 14690106
TI  - Morphine-sparing effect of nefopam by continuous intravenous injection after
      abdominal surgery by laparotomy.

PMID- 14690107
TI  - Photonic molecule lasing.
AB  - Lasing at resonantly coupled whispering-gallery mode frequencies is observed in
      photonic molecules consisting of bispheres of 4.2 and 5.1 microm in diameter
      placed in a silicon V-groove. We examine spatial profiles of photonic molecule
      modes by use of frequency-resolved imaging and reveal bonding and antibonding
      mode features. From the lasing threshold characteristics, we quantitatively
      measure the quality factor and the spontaneous-emission coupling ratio of the
      photonic molecule modes and confirm that strong coherent coupling leads to
      photonic molecule modes.

PMID- 14690108
TI  - Nonparaxial propagation of vectorial Gaussian beams diffracted at a circular
      aperture.
AB  - Based on the vectorial Rayleigh diffraction integral, the nonparaxial propagation
      of vectorial Gaussian beams diffracted at a circular aperture is studied. The far
      field and paraxial cases are treated as special cases of our general result. It
      is shown that for the apertured case the f parameter still plays an important
      role in determining the nonparaxiality of vectorial diffracted Gaussian beams,
      but both the f parameter and truncation affect the beam evolution behavior.

PMID- 14690109
TI  - Moments of the Wigner distribution of rotationally symmetric partially coherent
      light.
AB  - The Wigner distribution of rotationally symmetric partially coherent light is
      considered, and the constraints for its moments are derived. Although all odd
      order moments vanish, these constraints lead to a drastic reduction in the number
      of parameters that we need to describe all even-order moments: whereas in general
      we have (N + 1)(N + 2)(N + 3)/6 different moments of order N, this number reduces
      to (1 + N/2)2 in the case of rotational symmetry. A way to measure the moments as
      intensity moments in the output planes of (generally anamorphic) fractional
      Fourier-transform systems is presented.

PMID- 14690110
TI  - Optically tunable fiber grating transmission filters.
AB  - We propose and demonstrate single- and multiple-passband fiber grating
      transmission filters that are remotely tunable by exploitation of the optical
      pump-induced thermal effects in Er/Yb-codoped fiber sections. A repeatable,
      wavelength-independent induced phase shift of 0.1 pi/mW is obtained without
      hysteresis and anisotropic effects. A transmission extinction ratio of >23 dB
      with a 3-mW change in pump power is achieved.

PMID- 14690111
TI  - Holey optical fiber with circularly distributed holes analyzed by the radial
      effective-index method.
AB  - We analyze a holey fiber that consists of a circular distribution of air holes by
      the radial effective-index method. By this method, we show that the holey fiber
      is a leaky structure and its extended single-mode operation is governed by the
      differential leakage loss between the first two modes of the fiber. The effects
      of the hole size and the hole separation on the leakage losses of the first two
      modes are calculated. The leakage loss of the fundamental mode of the fiber is
      found to be comparable to that of a conventional holey fiber that has a hexagonal
      distribution of air holes.

PMID- 14690112
TI  - Ultracompact resonant filters in photonic crystals.
AB  - A novel design for an ultracompact, high-Q notch-rejection filter is presented,
      and an analytic expression for the transmission properties is derived. This
      folded directional coupler shares the properties of a Fabry-Perot resonator and a
      directional coupler. We compare and contrast the device to high-Q Fabry-Perot
      cavities in photonic crystal waveguides.

PMID- 14690113
TI  - Effect of chromatic dispersion on nonlinear phase noise.
AB  - We consider the combined effects of amplified spontaneous emission noise, optical
      Kerr nonlinearity, and chromatic dispersion on phase noise in an optical
      communication system. The effect of amplified spontaneous emission noise and Kerr
      nonlinearity were considered previously by Gordon and Mollenauer [Opt. Lett. 15,
      1351 (1990)], and the effect of nonlinearity was found to be severe. We
      investigate the effect of chromatic dispersion on phase noise and show that it
      can either enhance or suppress the nonlinear noise amplification. For large
      absolute values of dispersion the nonlinear effect is suppressed, and the phase
      noise is reduced to its linear value. For a range of negative values of
      dispersion, however, nonlinear phase noise is enhanced and exhibits a maximum
      related to the modulation instability found in amplitude fluctuations. Nonlinear
      phase noise is quenched by these effects even in dispersion-compensated systems;
      the degree of suppression is sensitively dependent on the dispersion map. We
      demonstrate these results analytically with a simple linearized model.

PMID- 14690114
TI  - Ultrasensitive long-period fiber gratings for broadband modulators and sensors.
AB  - We demonstrate long-period fiber gratings whose attenuation can be changed by 25
      dB over a 48-nm spectral band, with ambient-index changes of only 2.7 x 10(-4).
      To achieve this, the fiber waveguide is engineered to induce coupling between the
      core and a highly ambient-sensitive cladding mode with identical group
      velocities. The device schematic allows arbitrarily high index sensitivities to
      be achieved, which makes it an attractive platform for realizing sensors and
      modulators that respond to small index changes.

PMID- 14690115
TI  - Generation and detection of 80-Gbit/s return-to-zero differential phase-shift
      keying signals.
AB  - Nonlinear polarization rotation between a pump and a probe signal in a highly
      nonlinear fiber is used as a modulation process to generate 80-Gbit/s return-to
      zero differential phase-shift keying signals. Its performance is analyzed and
      compared with a conventional on-off keying modulated signal.

PMID- 14690116
TI  - Deep-notch, ultracompact long-period grating in a large-mode-area photonic
      crystal fiber.
AB  - An extremely short long-period grating (LPG) with strong resonance has been
      developed in a large-mode-area photonic crystal fiber (PCF) by use of the heat
      source of a CO2 laser. We believe that such a LPG in pure silica PCF is the first
      example to be obtained with the point-by-point technique. The fabrication method
      is simple and repeatable. The resulting LPG has 8 periods, written by a CO2
      laser, within a 2.8-mm length of fiber, which yields a deep notch of core
      cladding mode coupling of -31.5 dB at the telecommunication wavelength of 1529.2
      nm, with a FWHM of approximately 0.7 nm. The principal advantages of this LPG are
      that it is practical, cost effective, and compact.

PMID- 14690117
TI  - Enhancement of lateral resolution in confocal self-interference microscopy.
AB  - We describe confocal self-interference microscopy with enhanced lateral
      resolution. A uniaxial anisotropic crystal is used to cause interference between
      two linearly polarized beams that are reflected from the same pointlike object in
      the focal plane of the objective lens. Theory and the optimal design that
      maximizes the sensitivity of the interference signal are presented. A numerical
      experiment shows a 38% decrease in the lateral FWHM for simple confocal self
      interference microscopy.

PMID- 14690118
TI  - Multimode reverse-symmetry waveguide sensor for broad-range refractometry.
AB  - A sensor design that uses a grating-coupled multimode planar optical waveguide
      for absolute detection of the refractive indices of liquids or gases is
      presented. The waveguide consists of a simple 50-microm-thick, free-standing
      glass plate with air beneath it and the sample to be analyzed on top of it. This
      design offers a simple alternative to the well-known monomode waveguides, and,
      owing to its so-called reverse-symmetry configuration, a large detection range
      can be obtained.

PMID- 14690119
TI  - Self-referenced method for optical path difference calibration in low-coherence
      interferometry.
AB  - A simple method for the calibration of optical path difference modulation in low
      coherence interferometry is presented. Spectrally filtering a part of the
      detected interference signal results in a high-coherence signal that encodes the
      scan imperfections and permits their correction. The method is self-referenced in
      the sense that no secondary high-coherence light source is necessary. Using a
      spectrometer setup for spectral filtering allows for flexibility in both the
      choice of calibration wavelength and the maximum scan range. To demonstrate the
      method's usefulness, it is combined with a recently published digital spectral
      shaping technique to measure the thickness of a pellicle beam splitter with a
      white-light source.

PMID- 14690120
TI  - Resolution enhancement of pHe+ atomic line profiles measured with a pulsed dye
      laser and a Fizeau wavelength meter.
AB  - A Fizeau wavelength meter was used to compensate for fluctuations in the
      longitudinal mode structure and wavelength of a pulsed dye laser. The average
      laser linewidth was effectively narrowed by selection of laser pulses with a
      single longitudinal mode. These techniques were recently employed to measure some
      atomic transition wavelengths in pHe+ to fractional precisions greater than 1
      part in 10(7). The wavelengths were absolutely calibrated against iodine or
      tellurium lines by absorption spectroscopy or against neon or argon lines by
      optogalvanic spectroscopy.

PMID- 14690121
TI  - Shot-noise detection of ultrasound-tagged photons in ultrasound-modulated optical
      imaging.
AB  - We propose a new detection method for ultrasound-modulated optical tomography
      that allows us to perform parallel speckle detection with optimum shot-noise
      sensitivity, using a CCD camera. Moreover, we show that making use of a spatial
      filter system allows us to fully filter out speckle decorrelation noise. This
      method is confirmed by a test experiment.

PMID- 14690122
TI  - Enhancing early bladder cancer detection with fluorescence-guided endoscopic
      optical coherence tomography.
AB  - We report an experimental study of the possibility of enhancing early bladder
      cancer diagnosis with fluorescence-image-guided endoscopic optical coherence
      tomography (OCT). After the intravesical instillation of a 10% solution of 5
      aminolevulinic acid, simultaneous fluorescence imaging (excitation of 380-420 nm,
      emission of 620-700 nm) and OCT are performed on rat bladders to identify the
      photochemical and morphological changes associated with uroepithelial
      tumorigenesis. The preliminary results of our ex vivo study reveal that both
      fluorescence and OCT can identify early uroepithelial cancers, and OCT can detect
      precancerous lesions (e.g., hyperplasia) that fluorescence may miss. This
      suggests that a cystoscope combining 5-aminolevulinic acid fluorescence and OCT
      imaging has the potential to enhance the efficiency and sensitivity of early
      bladder cancer diagnosis.

PMID- 14690123
TI  - Multiharmonic-generation biopsy of skin.
AB  - Because it avoids the in-focus photodamage and phototoxicity problem of two
      photon-fluorescence excitation, multiharmonic-generation biopsy based on a 1200
      1300-nm light source could provide a truly noninvasive and highly penetrative
      optical sectioning of skin. We study multiharmonic-generation biopsy of fixed
      mouse skin. Our preliminary study suggests that this technique could provide
      submicrometer-resolution deep-tissue noninvasive biopsy images in skin without
      the use of fluorescence and exogenous markers.

PMID- 14690124
TI  - Wavelength division with three-dimensional couplers fabricated by filamentation
      of femtosecond laser pulses.
AB  - Refractive-index changes can be induced by filamentation of 800-nm, 1-kHz
      femtosecond laser pulses in silica glass. Two-dimensional translation of a 40
      microm-long filament leads to the formation of a curved waveguide because of
      bending by the previously induced refractive-index change. The fabrication of 2
      mm directional couplers to split the coupled beam into 1:1 at a wavelength of
      632.8 nm is demonstrated. The realization of three-dimensional directional
      couplers and wavelength division in the output from the couplers is also
      demonstrated.

PMID- 14690125
TI  - 14.5% near-normal incidence reflectance of Cr/Sc x-ray multilayer mirrors for the
      water window.
AB  - Cr/Sc multilayer mirrors, synthesized by ion-assisted magnetron sputter
      deposition, are proved to have a high near-normal reflectivity of R = 14.5% at a
      grazing angle of 87.5 degrees measured at the wavelength lambda = 3.11 nm, which
      is an improvement of more than 31% compared with previously published results.
      Elastic recoil detection analyses show that the mirrors contained as much as 15
      at. % of N and traces of C and O. Soft x-ray reflectivity simulations reveal
      interface widths of sigma = 0.34 nm and an exceptionally small layer thickness
      drift of approximately 1.6 x 10(-5) nm/multilayer period throughout the stack.
      Simulations show that a reflectivity of R = 25.6% is attainable if impurities and
      layer thickness drift can be eliminated. The abrupt interfaces are achieved with
      ion assistance with a low ion energy of 24 eV and high ion-to-metal flux ratios
      of 7.1 and 23.1 during Cr and Sc sputter deposition, respectively. In addition, a
      near-normal incidence reflectivity of 5.5% for the C VI emission line (lambda =
      3.374 nm) from a laser plasma source was verified.

PMID- 14690126
TI  - Continuous-wave operation of a single-frequency optical parametric oscillator at
      4-5 microm based on periodically poled LiNbO3.
AB  - We present a cw, Nd:YAG-pumped singly resonant single-frequency narrow-linewidth
      high-power optical parametric oscillator with idler tuning from 3.7 to 4.7
      microm. In this spectral range the absorption of the idler wave in the LiNbO3
      crystal is significant, causing the oscillation threshold to increase with a
      subsequent decrease in output power from 1.2 W at 3.9 microm to 120 mW at 4.7
      microm. The optical parametric oscillator's cavity was stabilized and mode-hop
      tuned with a rotatable solid etalon but with a subsequent reduction in idler
      power of as much as 50%. We demonstrated the usefulness for spectroscopy by
      recording the photoacoustic spectrum of a strong CO2 absorption, using a 24-GHz
      continuous idler scan.

PMID- 14690127
TI  - Enhanced second-harmonic generation from planar photonic crystals.
AB  - Strongly enhanced second-harmonic generation is observed from a two-dimensional
      square lattice GaAs/AlGaAs photonic crystal waveguide when the fundamental beam,
      the second-harmonic beam, or both beams resonantly couple to a leaky eigenmode. P
      polarized second-harmonic spectra are obtained for s-polarized, 150-fs pump
      pulses that are tuned from 5000 to 5600 cm(-1) and directed along the gamma-chi
      direction of the crystal for various angles of incidence. Compared with off
      resonant conditions, enhancements of >1200x in the second-harmonic conversion are
      observed for resonant coupling of both the fundamental and the second-harmonic
      fields to leaky eigenmnodes. The angular and spectral positions of the peaks are
      in good agreement with simulations.

PMID- 14690128
TI  - Optically tunable superprism effect in nonlinear photonic crystals.
AB  - An analysis of the tunable superprism effect in a two-dimensional nonlinear
      photonic crystal is presented. We show that, by shifting the photonic bands of
      the crystal through the Kerr effect induced by a pump beam, one can tune the
      refraction angle of a transmitted signal beam over tens of degrees. We also
      demonstrate that the optical power required to tune the refracted angle is
      dramatically reduced if the frequency of the pump beam is close to a bandgap
      edge.

PMID- 14690129
TI  - All-optical transistor action with bistable switching in a photonic crystal cross
      waveguide geometry.
AB  - We demonstrate all-optical switching action in a nonlinear photonic crystal cross
      waveguide geometry with instantaneous Kerr nonlinearity, in which the
      transmission of a signal can be reversibly switched on and off by a control
      input. Our geometry accomplishes both spatial and spectral separation between the
      signal and the control in the nonlinear regime. The device occupies a small
      footprint of a few micrometers squared and requires only a few milliwatts of
      power at a 10-Gbit/s switching rate by use of Kerr nonlinearity in AlGaAs below
      half the electronic bandgap. We also show that the switching dynamics, as
      revealed by both coupled-mode theory and finite-difference time domain
      simulations, exhibits collective behavior that can be exploited to generate high
      contrast logic levels and all-optical memory.

PMID- 14690130
TI  - Self-trapping of light in an organic photorefractive glass.
AB  - We report the first observation, to our knowledge, of self-trapping of light as
      well as optically induced focusing-to-defocusing switching in an organic
      photorefractive glass, owing to the orientationally enhanced photorefractive
      nonlinearity of the material.

PMID- 14690131
TI  - Soliton self-frequency shift in highly nonlinear fiber with extension by external
      Raman pumping.
AB  - A completely fiber-integrated, wavelength-tunable subpicosecond pulse source is
      demonstrated using the soliton self-frequency shift in highly nonlinear
      dispersion-shifted fiber from a 1.56-microm 10-GHz 400-fs signal. Solitons as
      short as 100 fs are obtained at tunable wavelengths as high as 1.72 microm. Raman
      gain from an external pump is used to extend the soliton self-frequency shift to
      longer wavelengths.

PMID- 14690132
TI  - Visualization of ferroelectric domains with coherent light.
AB  - Illumination of a lithium niobate or lithium tantalate crystal along the
      crystallographic c axis with coherent light while simultaneously applying an
      external electrical field through transparent electrodes allows real-time, in
      situ, nondestructive monitoring of ferroelectric domain patterns. Imaging of the
      optical near-field through a lens directly visualizes the domain walls, whereas
      the far-field yields averaged information about the spatial orientation of the
      domain boundaries.

PMID- 14690134
TI  - Optimum on-axis computer-generated hologram encoded into low-resolution phase
      modulation devices.
AB  - A computer-generated hologram with minimum spatial complexity is proposed for
      encoding arbitrary complex transmittance with low-resolution phase-modulation
      devices. The phase modulation of the proposed hologram is determined such that on
      axis reconstruction with high signal-to-noise ratio, optimum reconstruction
      efficiency, and the largest possible signal bandwidth can be obtained.

PMID- 14690133
TI  - Holographic three-dimensional display synthesized from three-dimensional fourier
      spectra of real existing objects.
AB  - A method of synthesizing computer-generated holograms of real existing objects is
      proposed that is based on a series of projection images of an incoherently
      illuminated object recorded from different perspectives. In accordance with the
      principles of computer tomography, the three-dimensional Fourier spectrum of the
      object is calculated by use of several projection images. A method of calculating
      a Fresnel hologram from the three-dimensional Fourier spectrum is proposed.
      Experimental results in the form of a computer simulation and optical
      reconstruction are presented.

PMID- 14690135
TI  - Coherent optical neural network that learns desirable phase values in the
      frequency domain by use of multiple optical-path differences.
AB  - A coherent optical neural network is proposed that has the learning ability to
      achieve desirable phase values in the frequency domain. It is composed of
      multiple optical-path differences whose lengths are different from one another.
      The system learns a phase value at each discrete position in the frequency domain
      by obeying the complex-valued Hebbian rule. The learning curve also agrees with
      theoretical evolution.

PMID- 14690136
TI  - Integrated optical Mach-Zehnder modulator based on polycrystalline BaTiO3.
AB  - Good-quality polycrystalline BaTiO3 thin films are deposited on MgO substrates by
      pulsed laserdeposition. The deposition parameters are optimized to achieve
      optical-quality films with an attenuation coefficient of 4 dB/cm at the 633-nm
      wavelength. Thin-film electro-optic Mach-Zehnder modulators are fabricated with
      standard lithography and ion-beam etching. The waveguides patterned by
      lithography are the ridge type, and they ensure single-mode propagation in the
      wavelength range of 633-1550 nm. An electro-optic coefficient of 22 pm/V is
      estimated for the polycrystalline BaTiO3 films.

PMID- 14690137
TI  - Clinical improvement in systemic sclerosis resulting from urokinase therapy
      explained by light and electron microscopy skin examination.
AB  - OBJECTIVE: In our previous work, patients affected by SSc were treated with
      intravenous urokinase and showed clinical improvement. In this study we used
      microscopy to document ultrastructural alterations occurring in sclerodermic skin
      from SSc patients treated with urokinase. METHODS: Ten patients with SSc were
      selected for this study. Skin biopsies were taken from the medial side of the
      right forearm on the third proximal on the volar surface. The patients were then
      treated with urokinase for 7 consecutive days. At the end of the treatment, the
      patients were examined and a new skin biopsy was taken close to the above
      mentioned zone of the forearm for optic and electron microscopy examination.
      RESULTS: The patients showed a gradual improvement of the skin after urokinase
      treatment. Raynaud's appeared to be less intense, and they had an increased
      articular range, with the restoration of movements that had previously been
      limited. Histological findings showed that, after treatment, skin alterations
      appeared attenuated, in particular the connective tissue showed a decreased
      density and inflammatory infiltrate was slight. Electron microscopy findings
      showed that collagen fibres appeared to have a more regular diameter, and the
      capillary vessels' lining was thicker, with fewer pinocytotic vesicles.
      CONCLUSION: These observations show that urokinase treatment seems to be an
      interesting therapeutic strategy to consider for the treatment of SSc.

PMID- 14690138
TI  - Analysis of B-cell clonality in the hepatic tissue of patients with Sjogren's
      syndrome.
AB  - OBJECTIVE: We investigated the incidence of B-cell clonality in the minor
      salivary gland and liver (extra-glandular lesion) of patients with Sjogren's
      syndrome (SS). We also compared B-cell clonality in the minor salivary gland and
      liver in the same individuals, and compared its incidence among patients with
      various liver diseases, such as primary biliary cirrhosis (PBC) and autoimmune
      hepatitis (AIH). METHODS: A minor salivary gland biopsy was performed on 35
      patients with SS (30 patients with primary SS, and five patients with secondary
      SS). A liver biopsy was performed on nine patients with SS associated with bile
      duct lesions, two patients with PBC, one patient with AIH, one patient with drug
      induced liver dysfunction, and three patients with viral hepatitis. DNA was
      extracted from each tissue sample and then subjected to Polymerase Chain Reaction
      (PCR). B-cell clonality was analysed by assessing the rearrangement of the
      immunoglobulin heavy chain (IgH) gene by PCR. RESULTS: B-cell clonality was
      confirmed in the minor salivary gland biopsy sample in 23 of the 35 patients
      (65.7%), and in the liver biopsy sample (non-exocrine organ involvement) in seven
      of the nine patients (77.8%). The presence or absence of B-cell clonality was
      investigated in both the minor salivary gland and liver in seven patients, but B
      cell clonality was confirmed in both tissues in only one patient, and the pattern
      of clonality in the minor salivary gland differed from that in the liver. B-cell
      clonality was detected in the liver of the PBC and AIH patients. CONCLUSION: B
      cell clonality is a phenomenon that is observed frequently in SS lesions in the
      salivary glands and liver. The appearance of B-cell clonality was shown to be
      attributable to antigen-driven clonal expansion.

PMID- 14690139
TI  - High proliferative potential colony-forming cells (HPP-CFCs) in the peripheral
      blood of rheumatoid arthritis patients with interstitial lung disease.
AB  - OBJECTIVE: To examine the presence of high proliferative potential colony-forming
      cells (HPP-CFCs) in the peripheral blood of rheumatoid arthritis (RA) patients
      with and without interstitial lung disease (ILD). METHODS: Peripheral blood
      mononuclear cells from 35 RA patients with and without ILD, 12 patients with
      infectious pulmonary diseases, 10 patients with idiopathic pulmonary fibrosis
      (IPF), and 20 healthy volunteers, were assayed for in vitro colony formation.
      RESULTS: HPP-CFCs were detected significantly more frequently in the peripheral
      blood of patients with ILD (11/14: 78%, p<0.05) than in that of patients without
      ILD (4/21: 19%). HPP-CFCs were not detected in the peripheral blood of patients
      with infectious pulmonary diseases, those with IPF or healthy volunteers.
      CONCLUSIONS: HPP-CFCs were frequently found in the peripheral blood of RA
      patients with ILD compared with those without ILD, suggesting the mobilization of
      HPP-CFCs from the bone marrow into the peripheral blood in association with ILD
      in RA.

PMID- 14690140
TI  - HLA-DRB1 genes and disease severity in rheumatoid arthritis in Turkey.
AB  - OBJECTIVE: Association with human leukocyte antigen (HLA)-DRB alleles, implicated
      in the aetiopathogenesis of rheumatoid arthritis (RA), is found to be different
      in various ethnic groups. This study aimed to investigate DRB1 alleles in RA
      patients in Turkey, and to examine the effect of these alleles on disease
      severity. METHODS: We performed PCR-based DRBI genotyping of 104 RA patients
      recruited from clinical settings and 110 healthy controls. HLA DRB1 alleles
      frequencies in RA patients and healthy controls were determined. Phenotype
      frequencies of patients and controls were compared. Disease severity was assessed
      by radiological erosion, presence of extra-articular involvement, and functional
      index. RESULTS: Significant differences were in the frequencies of DRB1*04 (46.2%
      versus 20.9%, p < 0.001), DRB1*0401 (10.6% versus 0%, p < 0.001), DRB1*0405 (8.7%
      versus 0%, p = 0.001), DRB1* 0404 (15.4% versus 3.6%, p < 0.01), DRB1*01 (21.2%
      versus 10.9%, p < 0.05) and DRB1*0101 (16.3% versus 5.5%, p = 0.01) between RA
      patients and controls. HLA-DRB1 alleles did not show any association with
      seropositivity, extra-articular involvement, radiological erosion, or functional
      index. CONCLUSION: Our results suggest that the HLA-DRB1 alleles, particularly
      HLA-DRB1*04 and subtypes, were associated with RA.

PMID- 14690141
TI  - A correlative study of clinical and histological findings of revision hip
      arthroplasty for rheumatoid arthritis and inflammatory joint disease.
AB  - OBJECTIVE: Primary hip arthroplasty in rheumatoid arthritis (RA) and other forms
      of inflammatory joint disease (IJD) is generally thought to be associated with a
      less favourable outcome in terms of implant survival and other complications.
      Whether the duration of implant survival correlates with the degree of rheumatoid
      like inflammatory changes in periprosthetic tissues is uncertain. METHODS:
      Histopathological changes in periprosthetic tissues obtained following revision
      surgery of 34 total hip replacements on 27 patients with IJD (RA 18 cases:
      ankylosing spondylitis three cases; juvenile chronic arthritis six cases) were
      examined. RESULTS: A heavy diffuse lymphocyte and plasma cell infiltrate +/-
      lymphoid aggregates was noted in 29% of cases in whom the mean implant survival
      was 5.6 years (range: 2-8 years). Where little or no lymphocytic infiltrate was
      noted in periprosthetic tissues, the mean implant survival was 8.6 years (range:
      1-17 years). Revision arthroplasty was not undertaken for early or late infection
      of a primary hip replacement. CONCLUSIONS: Our findings indicate that implant
      survival is less in those cases where there is a heavy lymphocyte and plasma-cell
      infiltrate in periprosthetic tissues. These findings suggest that the presence of
      a heavy chronic inflammatory-cell infiltrate in periprosthetic tissues is likely
      to be a contributory factor in causing early implant failure in RA.

PMID- 14690142
TI  - Receptor activator of nuclear factor kappaB ligand is expressed in resident and
      inflammatory cells in aseptic and septic prosthesis loosening.
AB  - OBJECTIVE: The pathogenesis of periprosthetic bone loss in aseptic and septic
      prosthesis loosening is unclear. There is considerable evidence that macrophages
      and osteoclasts play a key role in focal bone erosion and osteolysis around the
      prosthesis. RANKL (receptor activator of nuclear factor kappaB ligand) was shown
      to be a potent osteoclastogenic factor, and to be involved in bone destruction of
      myeloma and rheumatoid arthritis patients. Osteoprotegerin (OPG) is the natural
      RANKL inhibitor and may prevent periprosthetic bone loss. METHODS: The presence
      and distribution of RANKL, its receptor RANK and OPG in the periprosthetic
      interface of septically (n = 5) and aseptically (n = 6) loosened prostheses was
      examined by immunohistochemistry and immunoblotting. Additionally, the
      immunophenotype of the inflammatory infiltrate was determined [CD3, CD68, Ki-67,
      tartrate-resistant acid posphatase (TRAP)]. RESULTS: Aseptic and septic cases
      revealed a different histopathologic pattern. However, in all cases RANKL and
      RANK could be demonstrated in macrophages and giant cells. In addition, RANKL
      detected by immunoblot analysis proved to have the same molecular weight as a
      recombinant RANKL used as a control (31 kD and approximately 48 kD). OPG was
      detected in aseptic loosening, where macrophages showed a strong staining, but
      multinucleated giant cells were only weakly stained. A weak OPG staining was also
      observed in septic loosening. CONCLUSION: The pathogenesis of bone loss in septic
      loosening remains unclear, because the septic membrane bears few macrophages and
      giant cells, and half of them express OPG. In aseptic loosening, macrophages
      might not be stimulated by RANKL as a result of OPG expression. But
      multinucleated giant cells may be activated, as they hardly express OPG. They
      might be responsible for periprosthetic bone loss in aseptic loosening as a
      result of their RANKL and RANK expression.

PMID- 14690143
TI  - Assessment of trabecular bone structure in postmenopausal and senile osteoporosis
      in women by image analysis.
AB  - OBJECTIVE: The aim of the study was to assess bone trabecular structure in
      postmenopausal and senile osteoporosis. METHODS: The study was performed on
      transiliac specimens obtained from women with postmenopausal (n=10) and senile
      osteoporosis (n=10) and on normal autopsy bone (n=7). Digitalized
      microradiographs were analysed using dedicated software allowing for selection of
      longitudinal and transversal elements. RESULTS: Significant differences between
      transversal and control, as well as between longitudinal and control trabecular
      areas were observed in senile osteoporosis (p<0.005). In postmenopausal
      osteoporosis, such differences were found for longitudinal trabeculae only
      (p<0.005). Mean longitudinal trabecular area loss in senile and postmenopausal
      osteoporosis as compared to control group was 57.2% and 25.7%, respectively.
      Respective values for transversal trabecular area were 35.0% and 59.4%.
      CONCLUSION: Structural anisotropy of trabecular bone is greater in postmenopausal
      than in senile osteoporosis and control group. The method developed allows the
      evaluation of bone structures in radiographs with uneven exposure.

PMID- 14690144
TI  - Evaluation of the arthritis impact measurement scales (AIMS2) in Finnish patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the validity and reliability of the Finnish version of the
      Arthritis Impact Measurement Scales (AIMS2) in Finnish patients with rheumatoid
      arthritis (RA). METHODS: The reliability of the Finnish AIMS2 (Finn-AIMS2)
      questionnaire was assessed by test retest procedure and internal consistency of
      health-status scales. Construct validity was assessed by factor analysis, and
      convergent validity by correlation coefficients, with several disease activity
      and functional status variables. RESULTS: Internal consistency was 0.79-0.89 and
      test retest reliability 0.72-0.97. Factor analysis identified three factors:
      physical, psychosocial, and pain. There were strong correlations between the Finn
      AIMS2 health-status scales and the Health Assessment Questionnaire (HAQ).
      CONCLUSION: The Finn-AIMS2 questionnaire is a reliable and valid instrument for
      measuring health status in middle-aged Finnish patients with RA. The results also
      support the applicability of AIMS2 in comparisons in multinational studies.

PMID- 14690145
TI  - Intravenous cyclophosphamide improves cardiac dysfunction in lupus myocarditis.
AB  - We describe a Chinese woman who developed severe heart failure 3 years from the
      onset of systemic lupus erythematosus (SLE). Endomyocardial biopsy confirmed
      lupus myocarditis, with focal infiltrates of small lymphocytes and some
      polymorphic neutrophils. The conventional treatment for cardiac failure plus oral
      prednisolone failed to bring clinical and echocardiographical improvement until
      the addition of intravenous (i.v.) 'pulse' cyclophosphamide. Three weeks after
      i.v. cyclophosphamide treatment, there was significant improvement of her heart
      failure symptoms with improvement in the ejection fraction from 19% to 63%.

PMID- 14690146
TI  - Juvenile onset psoriatic arthritis in a patient with X-linked agammaglobulinemia
      (Bruton's disease).
AB  - We describe a 47-year-old male patient suffering from X-linked (or Bruton's)
      agammaglobulinemia with severe psoriatic arthritis (PsA), which started in
      childhood. PsA has been previously described in T-cell defective disorders, such
      as HIV infection, but our observation demonstrates that this rheumatic disease
      can also occur in subjects with B-lymphocyte cell functional impairment. Chronic
      inflammatory (bacterial?) involvement of the bowel could represent a pathogenetic
      connection between X-linked agammaglobulinemia and PsA.

PMID- 14690147
TI  - Etanercept induces improvement of arthropathy in chronic infantile neurological
      cutaneous articular (CINCA) syndrome.
AB  - Chronic infantile neurological cutaneous articular (CINCA) syndrome is a rare
      disorder of unknown aetiology with neonatal onset, characterized by severe
      arthropathy, persistent skin rash and central nervous system disease. Joint
      involvement may vary from minimal swelling to destructive arthritis, with
      inability to stand or walk. The most striking findings of CINCA syndrome are
      cartilage anomalies with epiphyseal modifications and abnormal ossification, for
      which a pathogenetic role of tumour necrosis factor-alpha (TNF-alpha) is
      postulated. We describe a 4-year-old child affected with CINCA syndrome and
      presenting progressive joint disease, in whom non-steroidal anti-inflammatory
      drugs (NSAID) and systemic corticosteroidal therapy had been ineffective.
      Etanercept, anti-TNF-alpha therapy, was administered over a 6-month-period
      resulting in a dramatic improvement of the arthropathy. This good response to
      anti-cytokine treatment supports our hypothesis that TNF-alpha might play an
      important role in the pathogenesis of CINCA syndrome, which needs to be evaluated
      and confirmed in further studies.

PMID- 14690148
TI  - Ochronotic arthropathy.
AB  - The authors report on 18 members of four generations of an alkaptonuric family.
      All three males in the third generation are clinically affected; two members of
      the family tree have undergone major joint surgery.

PMID- 14690149
TI  - No major differences in incidence of temporal arteritis in northern and western
      Norway compared with reports from southern Norway.

PMID- 14690150
TI  - Adapting the Rheumatoid Arthritis Quality of Life Instrument (RAQoL) for use in
      Sweden.

PMID- 14690151
TI  - Cancer survival in Sweden 1960-1998--developments across four decades.
AB  - This paper summarizes a comprehensive study of cancer survival in Sweden from
      1960 to 1998. A total of 1021421 persons and 40 different cancer sites were
      included in the analyses. The main outcome measure is the relative survival rate
      (RSR) for different sites and follow-up times after diagnosis. The 10-year RSR
      for all sites combined has increased steadily-from 26.6% among men and 41.8%
      among women in the 1960s, to 44.6% (men) and 57.6% (women) in the 1990s. The
      expectation of life for a person diagnosed with cancer today is about 7 years
      longer than that of one diagnosed during the mid-1960s. About 3 years are gained
      due to changes in the relative distribution of various cancer types and about 4
      years due to improved relative survival. During the 1990s substantial survival
      improvements were observed not only for uncommon types, such as testicular
      cancer, Hodgkin's lymphoma and some other haematologic malignancies, but also for
      cancer of the rectum, kidney and malignant melanoma. Survival for breast and
      cervical cancer also improved during the 1990s, but not that for pancreatic,
      liver or lung cancer.

PMID- 14690152
TI  - Oncolytic herpes viruses as a potential mechanism for cancer therapy.
AB  - Oncolytic viruses have been considered as a potential form of cancer treatment
      throughout the last century because of their ability to lyse and destroy tumor
      cells both in tissue culture and in animal models of cancer. However, it is only
      during the past decade that new molecular technologies have become available and
      understanding of genetic and molecular components of these viruses has increased
      to the point that they can be manipulated and made safe for use in treatment in
      humans. Thus there has been a revival of the concepts of conditionally
      replication-competent viruses and suicide gene therapy to supplement currently
      existing cancer therapies. While a wide variety of viruses have been closely
      studied for this purpose, herpes simplex virus type-1 (HSV-1) has received
      particularly close attention. The inherent cytotoxicity of this virus, if
      harnessed and made to be selective in the context of a tumor microenvironment,
      makes this an ideal candidate for further development. Furthermore, its large
      genome size, ability to infect cells with a high degree of efficiency, and the
      presence of an inherent viral-specific thymidine kinase gene add to its potential
      capabilities. This review explores work performed in this field and its potential
      for application in the treatment of cancers in humans.

PMID- 14690153
TI  - Carcinoid--a comprehensive review.
AB  - Carcinoid tumors originate from the neuroendocrine cells throughout the body and
      are capable of producing various peptides. Their clinical course is often
      indolent but can also be aggressive and resistant to therapy. We examined all
      aspects of carcinoid tumors including the molecular biology oncogenesis, role of
      angiogenesis, recent advances in imaging, and therapy. The Medline and Cancerlit
      databases were searched using carcinoid as the keyword. English language
      manuscripts were reviewed and relevant references from a total of 7741 were
      found. All titles were screened and all the relevant manuscripts were analyzed;
      we found 307 references pertinent to the history, epidemiology, clinical
      behavior, pathology, pathophysiology, molecular biology, radiologic imaging,
      supportive care of carcinoid syndrome, and results of therapeutic clinical
      trials. Management of patients with carcinoid tumors requires an understanding of
      the disease process and a multimodality approach. Introduction of long-acting
      somatostatin analogues has resulted in significant advances in the palliative
      care of patients with carcinoid syndrome. However, advanced carcinoid tumor
      remains incurable. Existing therapies for advanced disease have low biologic
      activity, high toxicity, or both. Clearly, more research is necessary in the
      areas of molecular biology, targeted therapy, and development of new drugs Future
      advances in this field need to focus on clinical and biological predictors of
      outcome. Early works in the area of tumor biology such as the role of p53, bcl-2,
      bax, MEN1, FGF TGF PDGF and VEGF expression are of interest and need to be
      explored further.

PMID- 14690154
TI  - Docetaxel in advanced gastric cancer--review of the main clinical trials.
AB  - The aim was to investigate the activity of docetaxel in advanced gastric cancer
      either as single agent or in combination with other drugs. A systematic review
      was carried out using the databases of Medline, Embase and CancerLit. Results
      from ASCO and ESMO meetings during 2002 were also included. Eight phase II trials
      focused on docetaxel as a single agent. Considering collectively the 262
      evaluable patients enrolled in these studies, the mean response rate (RR) was 19%
      (CI 95% 14-24%). Docetaxel was well tolerated with a dose-limiting
      myelosuppression (grade 3-4 neutropenia in 36-95% of cases). Adding fluorouracil,
      an RR ranging from 22% to 86% was registered, due to differences in populations
      studied (young vs elderly) and modalities of drug administration (continuous vs.
      bolus infusion). RRs for docetaxel-cisplatin combination were 56%, 37% and 36% in
      three phase II trials and 35% in a phase III trial. The addition of both
      cisplatin and fluorouracil to docetaxel did not increase toxicity. Randomized
      trials comparing docetaxel-cisplatin-fluorouracil with ciplatin-fluorouoracil or
      epirubicin-cisplatin-fluorouracil, the most commonly used regimens, are ongoing.
      The future results of the above phase III studies could indicate docetaxel as a
      key drug to improve treatment of patients with advanced gastric cancer.

PMID- 14690155
TI  - Stage and survival in breast cancer patients in screened and non-screened Danish
      and Swedish populations.
AB  - Comparisons between the Danish and Swedish Cancer Registry revealed a 9%
      difference in 5-year survival for breast cancer patients diagnosed between 1983
      and 1989. The purpose of this study was to determine whether previous differences
      in survival and stage still exist or whether the Danish figures approach those of
      the Swedish registry. Complete population-based cohorts of patients with breast
      cancer in the years 1996-1997 from well-defined areas in Denmark and Sweden were
      compared. The study regions were a Danish (Funen) and a Swedish (Malmo) county
      with mammography screening and two Danish counties without screening. No
      difference in extent of disease or survival was observed between screening areas
      regardless of country. However, there were significant differences in stage
      distribution and survival between screening populations and Danish non-screening
      populations, to the benefit of populations provided with a screening programme.
      Five-year survival was 5-6%, higher in screening populations than in Danish non
      screening counties. Corresponding disease-specific survival enhanced the
      difference. In a multivariate analysis increasing age, tumour size and stage
      decreased survival. Adjusting for these factors eliminated differences in
      survival according to country/county. Survival difference could be attributed to
      early diagnosis and favourable stage in populations offered mammography screening
      and was not related to nation. Denmark may, through early detection, approach the
      beneficial stage distribution and survival observed in Sweden.

PMID- 14690156
TI  - Predictors of quality of life of breast cancer patients.
AB  - Research has indicated that several demographic and clinical factors may affect
      the quality of life of breast cancer patients. Few studies, however, have
      sufficient sample sizes for multivariate analyses to be tested. Furthermore,
      several important factors, such as arm morbidity, communication and comorbid
      illness, have not been included in quality of life models The aim of this study
      was to predict the simultaneous effect of these factors on long-term quality of
      life. Breast cancer patients (n = 990) completed a quality of life survey,
      including the EORTC QLQ-C30, over five years. Clinical details were registered in
      the Munich Cancer Registry. Eleven predictors across eight quality of life
      domains were analyzed over a period of five years using a logistic regression
      model. Arm problems, communication, comorbidity, age, surgery. and, to a lesser
      extent, marital, educational and employment status were significantly associated
      with quality of life. Adjuvant therapy, medical insurance and pT category were
      not significant predictors. This study is the first to demonstrate the
      consistency and strength of arm dysfunction and doctor-patient communication on
      breast cancer patients' quality of life. These important factors in breast cancer
      care can be improved and should be regarded as a priority.

PMID- 14690157
TI  - Comparison of immunohistochemical and biochemical assay of steroid receptors in
      primary breast cancer--clinical associations and reasons for discrepancies.
AB  - Estrogen (ER) and progesterone receptor (PgR) status was analysed in paraffin
      embedded breast cancer material with immunohistochemical (IHC) technique and
      compared with corresponding analyses in cytosols (CYT). ER showed the same status
      (positive/negative) with both methods in 88% of the samples (352/402). The
      concordance was also high for PgR status (81% [321/394]). Besides values near cut
      off, heterogeneity in the distribution of receptor positive and negative nuclei
      within a tumour sample was the main reason for discordances. Histological type,
      presence of sclerosis, necrosis and non-invasive cells, and technical artefacts
      seem to be of only limited importance for explaining discordances All patients
      have been treated with adjuvant tamoxifen for two years. The two subgroups, which
      were ER(CYT)+/ ER(IHC) + or ER(CYT)-/ER(IHC) +, both had a significantly better
      progression-free survival (PFS; median follow-up: almost 6 years) than the
      ER(CYT)-/ER(IHC)- group (p < 0.001 and p = 0.007, respectively). The remaining
      group, ER(CYT)+/ER(IHC)-, had an intermediate PFS. For PgR, the associations with
      PFS were weaker, with significantly better PFS than the PgR(CYT)-/PgR(IHC)- group
      being found only for the PgR(CYT) +/PgR(IHC)- group (p = 0.03).

PMID- 14690158
TI  - Genetic counselling for cancer and risk perception.
AB  - The main aim was to investigate risk perception and psychological distress in
      individuals attending genetic counselling. A consecutive series of 86 individuals
      with a diagnosis and/or family history of breast, ovarian or colorectal cancer
      was included. Risk assessments were performed before and immediately after
      genetic counselling and at a one-year follow-up. Psychological distress was
      assessed 1 week before, and 6 weeks, 6 months and 1 year after genetic
      counselling. The number of individuals who correctly-estimated the general risk
      in the population increased significantly from 35%, before to 82% after
      counselling (p < 0.001). One year later, data on general risk estimates showed a
      significant reduction of the number of correct estimations to 51%, compared with
      directly after the counselling (p < 0.005). In total, 54% estimated their own
      lifetime risk correctly after the counselling, compared with 17% before (p <
      0.001) (those with a cancer diagnosis estimated the risk of their children
      developing cancer). One year later, the number of correct estimations had dropped
      to 28%. Before the counselling, the majority of the participants overestimated
      both the general risk and their own/children's risk. The participants experienced
      moderate levels of psychological distress before the counselling and a decrease
      of anxiety afterwards (p < 0.02). However, half of the participants reported
      moderate or high distress. There were no differences in psychological distress
      between those who estimated their risk/ children's risk as low, moderate or high
      or between those who over-, under- or correctly estimated their own/children's
      risk. Further investigations are needed to develop and adjust the risk
      information provided to the individual in order to avoid misunderstanding,
      especially as this information is going to be revealed to family members
      Counselling support should be offered to those individuals who experience
      psychological distress.

PMID- 14690160
TI  - Profiles and time course of acute radiation toxicity symptoms during conformal
      radiotherapy for cancer of the prostate.
AB  - Symptoms of gastrointestinal toxicity are dose-limiting for pelvic radiotherapy
      (RT). Existing toxicity registrations (RTOG/EORTC) are helpful in defining
      maximal tolerated doses, but tend to underestimate the total toxicity burden by
      excluding several minor complaints. We have applied a more detailed and
      quantitative recording of symptoms and related these scores to RT-induced
      endoscopic and histopathologic changes. Prevalence and severity of specific
      toxicity symptoms were recorded before, during (weeks 2 and 6) and 2 and 8 weeks
      after RT in 96 patients undergoing external beam RT for localized prostate
      cancer. RTOG/EORTC acute toxicity and ad hoc total toxicity scores (TTS) were
      recorded. TTS scores were calculated by adding scores based on visual analog
      scale (VAS) grading of individual symptoms Fifty of the patients also underwent
      sequential proctoscopy with mucosal biopsy. Individual symptoms increased, but
      differed in prevalence and intensity during and after RT TTS increased during the
      entire treatment course in spite of normalizing histopathologic and endoscopic
      changes from week 2 onwards. Twenty-seven patients had no RTOG/EORTC toxicity,
      four had grade 3 and none had grade 4 toxicity. All patients with grade 0 had
      increased TTS. Thus, TTS appeared more sensitive than RTOG/EORTC scoring. The
      study demonstrates that multiple toxicity symptoms contribute to total toxicity
      in response to pelvic RT. TTS is a feasible and sensitive method for detecting
      and quantifying acute toxicity and unveils morbidity which remains hidden with
      the RTOG/EORTC score system. The development and timing of symptoms may give
      clues to pathogenesis, treatment, and prophylaxis.

PMID- 14690159
TI  - Clodronate as a single-dose intravenous infusion effectively provides short-term
      correction of malignant hypercalcemia.
AB  - The efficacy and safety of a single intravenous (I.V.) infusion of clodronate
      1500 mg or 900 mg was compared with a single I.V. infusion of pamidronate 90 mg
      in the treatment of malignant hypercalcemia. Primary efficacy data from two
      separate, but parallel, randomized double-blind controlled multi-center studies
      (N = 63), involving patients with malignant hypercalcemia (S-Ca(cor) > 2.68
      mmol/l), were pooled along with results from a study (N = 4), in which an open
      I.V. phase was followed by a randomized oral phase. The primary efficacy
      variable, the proportion of normocalcemic patients at day 5 could be evaluated
      from 51 subjects. Of them, 21 were in the clodronate 1500 mg group, 10 in the
      clodronate 900 mg group and 20 in the pamidronate 90 mg group. After the
      rehydration, the patients were given a single I.V. infusion of clodronate 1500
      mg, clodronate 900 mg or pamidronate 90 mg. The patients were followed up for
      five days and S-Ca(cor) was measured daily. At day 5, a total of 16 patients
      (76%) in the clodronate 1500 mg group, six patients (60%) in the clodronate 900
      mg group and 17 patients (85%) in the pamidronate 90 mg group were normocalcemic,
      the differences between the treatment groups being statistically non-significant.
      The differences in the mean S-Ca(cor) between the treatment groups were
      statistically non-significant. I.V. clodronate given either as 900 mg or 1500 mg
      single-dose was safe and well tolerated.

PMID- 14690161
TI  - Androgen-independent prostate cancer--the clinical problem of a growing pelvic
      tumour.
AB  - This retrospective study describes three clinically different groups of patients
      with symptomatic androgen-independent prostate cancer (AIPC) referred to
      palliative radiotherapy (RT): those with a symptomatic pelvic tumour and pelvis
      confined disease (M0 P-RT: 35 patients), those with a symptomatic pelvic tumour
      and distant metastases (M + P-RT: 97 patients) and those with painful bone
      metastases (BM-RT: 193 patients). The study emphasises the need of a combined
      surgical and radiotherapeutic palliation in AIPC patients with symptomatic pelvic
      tumours. Median overall survival from time of palliative RT was 19, 9 and 8
      months for M0 P-RT, M + P-RT and BM-RT patients, respectively (p < 0.001). The
      significantly prolonged natural course of P-RT patients without distant
      metastases has to be accounted for in clinical trials of AIPC patients in whom
      survival represents an endpoint. Furthermore, the optimal palliation regimens for
      P-RT patients are still to be defined.

PMID- 14690163
TI  - Stage I and II mobile tongue carcinomas treated by external radiation and gold
      seed implantation.
AB  - The purpose of this study was to analyze the influence of a protocol
      modification, in which the use of gold seeds was extended and elective neck
      irradiation was applied, on the treatment results of early carcinoma of the
      tongue. We analyzed 225 patients with Stage I (93 patients) and Stage II (132
      patients) squamous cell carcinomas of the oral tongue. We compared the results
      between the two periods before (171 patients) and after (54 patients) the
      modification. The main alterations were the expanded use of gold seeds for tumors
      less than 5 mm in thickness and the application of elective irradiation for T2
      tumors. The 5-year primary control and survival rates improved from 81% to 97%
      and from 81% to 93%, respectively. The occurrence of late complications-lingual
      muscle and mandibular bone necroses-was found not to deteriorate after the
      modification. We concluded that the modification was adequate.

PMID- 14690162
TI  - Treatment of squamous cell carcinoma of the oral cavity, oropharynx and
      hypopharynx--an analysis of 174 patients in south western Finland.
AB  - The purpose of this study was to determine the efficacy and feasibility of full
      dose preoperative radiation therapy (RT) in head and neck cancer presenting in
      the oral cavity, oro- and hypopharynx, within a single university hospital
      district. During a seven-year period, 1989 to 1995, 174 patients with squamous
      cell carcinoma (SCC) of the oral cavity (OC, 70% of all patients), oropharynx
      (OP, 15%) and hypopharynx (HP, 15%) were referred to Turku University Central
      Hospital. All patients were seen by a tumor board consisting of an ENT (ear-nose
      throat) head and neck surgeon, a radiation oncologist and a dentist. Potentially
      curative treatment was given to 142 patients. Of these, 88 (62%) had preoperative
      RT, 6 (4%) postoperative RT, 34 (24%) definitive RT and 14 patients (10%) were
      treated with surgery only. The radiation dose was > or = 50 Gy. averagely 64 Gy.
      The major endpoints of the study were local control, overall survival and major
      complications of the combined treatment. The 5-year relative survival rate (RSR)
      was 40% for all, and 43% for patients treated with curative intent. For these,
      the local control at 5 years was 60%; the disease-specific 5-year survival rate
      was 65% for the patients with lingual SCC, 45% for those with other oral tumor
      localizations. 64% for the oropharynx patients and 47% for those with tumor in
      their hypopharynx, while it was 55% for all patients. The preoperative
      radiotherapy was fairly well tolerated. Ten (7%) of the patients treated with
      curative intent suffered major complications, and four patients had evidence of
      osteoradionecrosis. With the exception of patients with early SCC the outcome
      remains rather poor in this group of cancer patients who often have marked co
      morbidity. In our opinion, preoperative radiotherapy to a dose of 62-64 Gy can
      safely be given, and remains a feasible means to treat patients with oral,
      oropharyngeal or hypopharyngeal cancer.

PMID- 14690164
TI  - Laryngeal carcinoma--multivariate analysis of prognostic factors in 1252
      consecutive patients treated with primary radiotherapy.
AB  - Multivariate analyses of prognostic factors were carried out in 1252 consecutive
      patients with laryngeal squamous cell carcinoma treated with primary radical
      radiotherapy. Ten percent of patients had positive neck nodes Most of the
      patients were in stage I (48%), the remainder in stage II (24%), III (18%) and IV
      (10%). Of these patients, 746/1 252 (60%) were controlled by primary treatment
      but 506/1 252 (40%) had residual tumor or recurrent disease. The larynx was
      preserved in 62% of patients. The 5-year actuarial values for disease-specific
      and overall survival were 78% and 60%, respectively. The results of a univariate
      analysis showed multiple significant prognostic factors, and in a Cox
      proportional hazards model it was found that gender and T-classification were
      significant for T-failure, locoregional failure, death from cancer and death from
      all causes. The region of origin, nodal involvement, differentiation and
      pretreatment hemoglobin value were significant for several of the above-mentioned
      endpoints. Laryngeal carcinoma is curable when treated with primary radiotherapy,
      and this treatment confers a high degree of organ preservation. Independent
      prognostic factors in the multivariate analyses were gender, region of origin, T
      stage, nodal involvement, differentiation and hemoglobin.

PMID- 14690165
TI  - Therapeutic outcome of extranodal NK/T-cell lymphoma initially treated with
      chemotherapy--result of chemotherapy in NK/T-cell lymphoma.
AB  - The therapeutic outcome of chemotherapy in NK/T cell lymphoma (NTCL) has not been
      well documented until now. The aims of this study were to investigate the outcome
      of chemotherapy and to evaluate the clinical factors influencing the
      responsiveness to chemotherapy. Between 1995 and 2000, 59 patients received
      anthracycline-based chemotherapy as an initial treatment. Forty-five patients had
      nasal NTCL, whereas 14 had extranasal NTCL. Forty-one patients had stage I/II and
      18 had stage III/IV disease. Epstein-Barr virus status was positive in 67.6% of
      cases. The results of initial chemotherapy were complete remission in 35.6% of
      the patients, 2-year disease-free survival in 22.9% and 2-year overall survival
      in 44.2%. Adjuvant radiotherapy after chemotherapy did not improve outcome in
      stage I/II nasal NTCL. The International Prognostic Index was a significant
      prognostic factor of complete remission rate, and stage was also significant for
      disease-free survival.

PMID- 14690166
TI  - 2-Chloro-deoxyadenosine induces durable complete remission in Castleman's disease
      but may accelerate its transformation to non-Hodgkin's lymphoma.
AB  - There is currently no consensus on the best treatment for unresectable hyaline
      vascular variant or for multicentric Castleman's disease (MCD), because none of
      the reported regimens have consistently produced complete response or durable
      remission in the majority of patients In the present study, we report on the use
      of 2-CdA (2-chloro-deoxyadenosine) in three patients, two of them with MCD and
      one with unresectable hyaline-vascular type disease. Relapse-free survival of the
      responding patients was 24 and 20 months. Later, both patients evolved to non
      Hodgkin's lymphoma (NHL) (diffuse large B-cell lymphoma and peripheral T-cell
      NHL, respectively). 2-CdA typically causes a long-lasting state of
      immunodeficiency and the profound influence of this drug on the immune system has
      raised questions concerning the emergence of secondary neoplasms after its use.
      Therefore, it is reasonable to conclude that: 1) 2-CdA can induce durable
      complete remission in MCD patients but unfortunately it cannot cure the disease;
      2) the possibility that 2-CdA may accelerate the transformation of MCD to NHL
      cannot be ruled out.

PMID- 14690167
TI  - Exhaled nitric oxide is highly increased in a case of Hodgkin's disease.

PMID- 14690168
TI  - A sarcoid-like reaction in a patient with hemangiopericytoma--mediastinal
      lymphadenopathy resulting in confusion about therapy.

PMID- 14690169
TI  - Histone acetylation and cancer.

PMID- 14690170
TI  - Actin filaments in human renal tubulo-interstitial fibrosis: significance for the
      concept of epithelial-myofibroblast transformation.
AB  - Epithelial-myofibroblast transformation has been argued as playing a role in
      tubulo-interstitial fibrosis. To investigate this hypothesis, we examined 9 renal
      biopsy specimens from patients with chronic renal disease by light and electron
      microscopy. In all cases, electron microscopy confirmed light microscope
      observations in relation to tubulo-interstitial fibrosis-tubular atrophy,
      accumulation of extracellular matrix and of mesenchymal interstitial cells, and
      infiltration by inflammatory cells. Tubular epithelial cells (TECs) contained
      bundles of actin filaments: mostly lacking the focal densities typical of smooth
      muscle myofilaments. The interstitium contained collagen and inflammatory cells.
      Some endothelial cells showed bundles of myofilaments. Free mesenchymal cells in
      the matrix were spindled and had sparse rough endoplasmic reticulum (rER), small
      attachment plaques, few actin filaments and no lamina. In one case,
      myofibroblasts (defined by abundant rER, myofilaments and fibronexuses) were
      present. Most of the mesenchymal cells, therefore, did not correspond to
      myofibroblasts, nor to classical fibroblasts because of the sparse rER and the
      presence of actin filaments. We therefore called these cells myoid stromal cells,
      regarding them as stromal mesenchymal elements showing partial activation towards
      a smooth-muscle phenotype. This paper demonstrates a greater phenotypic
      complexity of actin-containing stromal cells in the interstitium than previously
      appreciated, with only a minority conforming to true or fully differentiated
      myofibroblasts. The widespread presence of actin (as filaments or
      immunoreactivity) in both TECs and interstitial cells, combined with the absence
      of evidence of intermediate forms or of migration from epithelium into
      interstitium, may point to epithelium and interstitium as separate targets for
      actin upregulation as an alternative hypothesis to epithelial-myofibroblast
      transformation.

PMID- 14690171
TI  - Ultrastructural study of Entamoeba invadens encystation and excystation.
AB  - In the life cycle of Entamoeba species, the cyst and all the processes associated
      to it have been poorly studied. Entamoeba invadens, a serpent's parasite, has
      been commonly accepted as a model for the study of encystation and excystation.
      Here we analyzed through scanning and transmission electron microscopy the in
      vitro morphological differentiation of both processes. During encystation, the
      formation of an irregular net of fibrillar material on the surface of precysts
      was observed. In thin sections of cryofixed and cryosubstituted specimens,
      abundant vacuoles containing a microfibrillar material of similar appearance to
      the structural components of the cyst wall were found in the cytoplasm. Assays
      with a calcofluor probe on cryosections of encysting trophozoites and precysts
      showed the presence of fluorescent circular cytoplasmic structures. In the cyst
      stage, the fluorescence was located on the surface. During excystation, the
      detachment of the metacyst from the cyst wall was observed through scanning
      electron microscopy. Metacysts endocyting amorphous material which may correspond
      to cyst wall residues were commonly found. By transmission electron microscopy
      the formation of a crescent-shaped space between the plasma membrane and the cyst
      wall was observed. Abundant small electrondense bodies were found in the
      cytoplasm. Many of them were in close apposition to the plasma membrane and
      frequently some of them were seen projecting towards this newly formed space. Our
      results suggest that the microfibrillar content of the vacuoles corresponds to
      the cyst wall material, that the electrondense bodies may be involved in the
      excystation process, and that part of the cyst wall residues may be endocyted by
      the parasite.

PMID- 14690172
TI  - Protein phosphorylation during the process of interaction of Toxoplasma gondii
      with host cells.
AB  - Previous studies have shown that tachyzoites of Toxoplasma gondii were able to
      penetrate into macrophages using two mechanisms: phagocytosis and active
      penetration. We show here that previous incubation of the macrophages or the
      parasites with staurosporine, a wide range inhibitor of protein kinases,
      tyrfostin and genistein, specific inhibitors of tyrosine kinases, significantly
      interfered with the process of parasite-macrophage interaction. Staurosporine
      treatment induced the formation of many filopodium-like surface projections of
      the macrophages and markedly increased the attachment of the tachyzoites to the
      cell surface. Genistein inhibited about 50% penetration of T. gondii into
      macrophages. Previous incubation of tachyzoites with genistein also significantly
      inhibited their attachment to and penetration into the macrophages. Confocal
      laser scanning microscopy was used to locate phosphoproteins in macrophages
      interacting with tachyzoites. Antiphosphotyrosine antibodies labeled the surface
      of macrophages, but not L929 cells, incubated in presence of T. gondii, even
      those cells did not show associated parasites. Anti phosphotyrosine,
      phosphothreonine and phosphoserine antibodies labeled the region surrounding the
      parasitophorous vacuoles. These observations suggest that protein phosphorylation
      is a key event in the process of T. gondii-host cell interaction.

PMID- 14690173
TI  - X-ray contrast media induce aortic endothelial damage, which can be prevented
      with prior heparin treatment.
AB  - X-ray contrast media induce damage to the endothelial layer of vessels and
      initiate the formation of thrombosis, which is a complication for clinical
      diagnostic procedures. The future determination of the mechanisms, which underlie
      the damaging effect of X-ray contrast medium on vascular wall cells, especially
      vascular endothelium and possible prevention of this damage by vasoprotector,
      will result in a larger application in diagnostic procedures. The aim of the
      present study is to analyze the effect of X-ray contrast media (Verographin,
      Iodamid and Iodolipol) on the arterial endothelium morphology by using
      ultrastructural techniques (scanning and transmission electron microscopy, SEM
      and TEM respectively). Experiments have been carried out on New Zealand white
      rabbits (6 month old) and Wistar rats (6-8 month old) after a single injection of
      X-ray contrast media with and without prior heparin treatment. Control groups of
      animals were exposed to the same procedure but without X-ray contrast media
      injection and only received isotonic saline solution. The following time points
      were selected: 1, 6, 24, 72 h and 7 days. At the end of the experiments, animals
      were anesthetized by pentobarbital and then perfused with a balanced buffer for 1
      min and followed by perfusion fixation with Karnovsky's fixative containing
      buffered solution of 2.5% paraformaldehyde and 2.5% glutaraldehyde (pH 7.36) at
      least 30 min. The aortic tissue was removed and immediately placed into a fresh
      portion of the same fixative. Aortic samples were then prepared for scanning and
      transmission electron microscopy (SEM and TEM respectively). Immediately after
      the injection of X-ray contrast media, the number of microvilli and blebs on the
      luminal surface of the endothelial cells (EC) significantly increased. Very
      often, nuclear portions of the EC sharply protruded into the vessel lumen.
      Clusters of spindle-shaped EC were seen throughout the endothelial monolayer.
      These changes persist through the 72-h period after X-ray contrast media
      injection. Moreover, the desquamation and denudation of the EC from the monolayer
      is often observed and this is accompanied by the presence of a microthrombus on
      the vessel surface. Seven days after the post-injection period, endothelial
      monolayers still show severe damage, which often coexists with the presence of a
      different sized microthrombus on the vessel surface. However, the degree of
      lesion formation in most areas is substantially decreased as compared to the
      early period of post-injection (24 and 72 h). Heparin treated group shows intact
      morphology similar to the control experimental groups (saline injected group).
      Infrequently, minimal morphological changes of the endothelium, such as increased
      number of microblebs and microvilli, were seen with heparin treatment. We
      conclude that the negative side effects of the X-ray contrast media can be
      eliminated by a single injection of heparin or other vasoprotector prior to the
      diagnostic procedure.

PMID- 14690174
TI  - The Golgi apparatus of satellite cells associated with spinal ganglion neurons:
      changes with age in the rabbit.
AB  - We studied the Golgi apparatus in the satellite cell sheaths enveloping spinal
      ganglion neurons of rabbits aged 12, 42, and 79 months. We found neither
      structural changes nor indications of peripheral displacement of this organelle
      with advancing age. The mean percentage of cytoplasmic volume occupied by the
      Golgi apparatus decreased significantly passing from young adult to old rabbits.
      This decrease was only in very minor part a consequence of lipofuscin
      accumulation, so that the ratio between the total volume of the Golgi apparatus
      and the functionally active volume of cytoplasm decreased with age. The mean
      cytoplasmic volume of perineuronal satellite cell sheaths did not change
      significantly with increasing age, whereas the total volume of the Golgi
      apparatus within these sheaths decreased significantly with age. This decrease
      strongly suggests that the activity of satellite cells diminishes in old age,
      further suggesting that these cells are unable to compensate for the decrease in
      the neuronal metabolism that a number of authors have described in old age.

PMID- 14690175
TI  - The formation and dissolution of the bridge-partitioning complex in intercellular
      bridges of dividing germ cells in the testis of the golden hamster.
AB  - Intercellular bridges (IBs) connecting mammalian germ cells get transiently
      closed during cell divisions by a structure termed the bridge-partitioning
      complex (BPC). It is composed of a compact stack of transverse endomembrane
      cisterns that are laterally anchored to the thickened bridge wall (bridge
      density). Studying male gonads of the golden hamster, the formation of the BPC
      during prophase/prometaphase transition and its dissolution in late telophase of
      germ cell divisions was followed. 1) There are strong indications for the
      involvement of a microtubule-based transport mechanism in the movement of
      membrane-bound vesicles toward and away from the site of the BPC during its
      formation or dissolution, respectively. 2) The BPC is built up exactly within the
      central segment of the IB carrying the bridge density. This feature suggests a
      specific interaction between components of the (forming) BPC and the material
      constituting the bridge density. The bridge density might be involved in locally
      directing the process of BPC formation within germ cell IBs.

PMID- 14690176
TI  - Morphology of the male genitalia and sperm fine structure in siluroid fish.
AB  - Morphology of male genitalia and sperm fine structure of 4 siluroid fish,
      Callichthys thoracatus (Callichthyidae), Dysichthys coracoideus (Aspredinidae),
      Mystus armatus (Bagridae) and Ancistrus triradiatus (Loricariidae) were studied.
      In Dysichthys coracoideus and Ancistrus triradiatus the male genitalia consisted
      of paired testes and spermatic ducts but had no seminal vesicles. In Callichthys
      thoracatus the male genitalia had also paired seminal vesicles which were
      separated from the testis and emptied into the spermatic duct. Also in Mystus
      armatus seminal vesicles were found. They were not separated from the testes but
      the seminiferous tubules changed into seminal vesicle lobes which finally emptied
      into the spermatic ducts. All the investigated species had simply organized
      aquasperms typical for external fertilizing teleosts which were characterized by
      an ovoid or elliptoid head, by a small midpiece and by the absence of an
      acrosome. The spermatozoa of Dysichthys coracoideus and Mystus armatus were
      biflagellate, while they were monoflagellate in Ancistrus triradiatus and
      Callichthys thoracatus. The proximal centriole was reduced in Dysichthys
      coracoideus and Mystus armatus and the basal body attached to the nucleus. Single
      mitochondria were found in Dysichthys coracoideus, Ancistrus triradiatus, and
      Callichthys thoracatus. On the contrary, in Mystus armatus mitochondria were
      fused to a more complex chondriosome.

PMID- 14690177
TI  - Biological and ultrastructural effects of the anti-microtubule agent taxol
      against Trypanosoma cruzi.
AB  - Microtubules play fundamental roles in eukaryotic cells and have been
      investigated as target for drugs. Several studies showed the potential use of
      anti-microtubule agents against pathogenic protozoa. Taxol has been intensively
      studied in Leishmania spp. and microtubules have been considered as a promising
      antileishmanial drug target. It has been also shown that taxol interferes with
      the proliferation of Trypanosoma cruzi, leading to morphological alterations and
      interruption of nuclear division and cytokinesis. In the present work we show
      that T. cruzi bloodstream trypomastigotes were much more susceptible than
      epimastigotes, and in both forms taxol caused severe ultrastructural damage,
      especially associated to changes in the shape of the parasites. In
      trypomastigotes, different degrees of body contortion along the longitudinal axis
      and a marked dilatation of the flagellar pocket were detected. Treated
      epimastigotes presented a decrease in the electron density of the mitochondrial
      matrix, absence of mitochondrial cristae and an increase in the number of lipid
      droplets. Bizarre multi-flagellar epimastigotes were also detected, suggesting an
      interruption of the cytokinesis. Taxol caused no noticeable ultrastructural
      alterations on sub-pellicular and flagellar microtubules of both evolutive forms
      of T. cruzi. As already described in the literature, such structures in
      trypanosomatids are very resistant to microtubule disrupters when compared to
      those in mammalian cells. Taxol prevented the endocytosis of albumin-gold
      complexes by epimastigotes, and this result could be associated to the loss of
      the dynamic stability of the microtubules of the cytostome.

PMID- 14690178
TI  - The spherule cells of Holothuria polii Delle Chiaie, 1823 (Aspidochirota,
      Holothuroidea) during brown body formation: an ultrastructural study.
AB  - Spherule cells are specific types of coelomocytes found in both the coelomic
      fluids and the connective tissues of many echinoderm groups and are characterised
      by large membrane-bound inclusions which completely fill their cytoplasm. In
      holothurians they are present in massive number in the coelomic fluids and are
      employed in brown body formation. Brown bodies are products of encapsulation and
      mainly consist of phagocytic amoebocytes and spherule cells: they surround
      foreign particles too large to be ingested by circulating phagocytes. During
      brown body formation, phagocytic amoebocytes flatten out over the surface of
      foreign particles to form unpigmented nodules which eventually aggregate into a
      single brown body in which many spherule cells are entrapped. Morphological
      modifications of spherule cells were studied in Holothuria polii following the
      induction of brown body formation by intracoelomic injection of sheep
      erythrocytes. Our ultrastructural observations provide evidence that the granules
      undergo typical exocytosis after previous disorganisation of their content and
      suggest a specific secretory activity for the spherule cells. The possible
      functional role of the secreted vacuolar material in brown body formation is
      discussed.

PMID- 14690179
TI  - Cellular response to an intravascular catheter.
AB  - Central venous catheters are commonly used in clinics for the administration of
      infusion therapy and total parenteral nutrition. Catheter occlusion is the most
      common noninfectious complication associated with the long-term use of such
      devices. The cause of catheter occlusion is the formation of a tissue sleeve
      around the catheter. In this study, a rat model was used to investigate the
      effects of integrin antagonist peptide on the growth of the tissue sleeve around
      the jugular catheters. When integrin antagonist peptide was injected
      subcutaneously, twice daily, for 3 days, at a dosage of 10 mg/kg of body
      weight/day, the growth of the tissue sleeve was reduced by 40%, as compared to
      rats injected with saline or control peptide. Morphological study of the tissue
      sleeve indicated that catheter-related damage to the nearby endothelial cells was
      associated with the adhesion of platelets and leukocytes to the injured
      endothelium and accumulation of fibrin in the vicinity. This proposed sequence of
      events resulted in an increase in the thickness of the tissue sleeve and changes
      in sleeve transparency.

PMID- 14690180
TI  - Ultrastructural alterations in cortex of adrenal gland caused by the toxic effect
      of bee (Apis mellifera) venom.
AB  - Bee accidents incidence is underestimated because many people do not consult to
      the physicians. Here it is described for the first time the severe mice adrenal
      gland damage induced by Apis mellifera venom. Biopsy specimens were obtained from
      mice adrenal gland and after sample preparation observed in Hitachi H-7100
      electron microscope. In this work the ultrastructural analysis showed, 6 h after
      injection, a non homogeneous smooth endothelial reticulum, and in some places
      loss of plasma membrane. The fenestrae spaces were bigger and detritus in the
      capillary lumen were observed. Erythrocytes were seen in a cortical cell. After
      48 h of venom injection, expanded fenestrae were observed. Capillary basal
      membrane was interrupted. Myelin-like figures and autophagic vacuoles were
      noticed. Swollen smooth endoplasmic reticulum elements and endothelial unfolding
      to the light were seen. Moreover, swollen Golgi and mitochondria were observed,
      in some places forming myelinic-like figures. At 144 h after venom injection,
      widened spaces were noticed in capillary fenestrae. Cellular section showed
      swollen and lost smooth endoplasmic reticulum elements. Smooth endoplasmic
      reticulum tubules disappearance suggested non steroidogenesis. In conclusion, we
      suggest that some of the bee envenoming human clinical manifestations, as is
      observed in mice, are determined by suprarenal gland damage produced by toxins
      present in this venom.

PMID- 14690182
TI  - The development of the chicken small intestine: a scanning electron microscopy
      study.
AB  - The surface pattern of the small intestine of the chicken was studied using SEM
      in stages ranging from 11th day of foetal development to 60 days of post-natal
      life. The definite villi of the small intestine were preceded by the development
      of the previllous ridges. The villi were finger like and of unequal length during
      incubation. After hatching, gradually, the villi were longer, well formed with
      furrows along their sides. Respectively, the crypts, being present at late
      incubation, increased with age. Columnar epithelial cells with dense microvilli
      lined the luminal surface of the intestine with obvious goblet cells openings
      among them.

PMID- 14690181
TI  - An implanted hamster greene melanoma expressing multiple host-tissue
      differentiation.
AB  - After Greene melanoma tissue had been implanted subcutaneously in a Syrian Golden
      Hamster and allowed to grow there for 10 days, its tissue components were
      examined by transmission electron microscopy. Amelanotic and melanotic tumor
      cells, blood vessels and nerve fibers were present. In the amelanotic and
      melanotic tumor cells the rough endoplasmic reticulum was colonized by spherical
      endogenous retroviruses, whereas no virus particles could be detected in
      endothelial or other cells. The cell-type-specific viruses thus mark separate
      cell lineages and indicate that blood vessels in Greene melanoma are not formed
      by tumor cells, so that the 'vasculogenic mimicry' currently under controversial
      discussion for other melanomas is not involved here. The tumor also comprised
      smooth muscle cells, skeletal muscle fibers and collagen fibers. This remarkable
      finding implies that tumor growth involves not only the stimulation of
      angiogenesis and neurogenesis by various growth factors, but also the activation
      of other cells/tissues in the adjacent host tissues. This influence of the
      surrounding host tissue produces the observed epiphenomena and can also cause the
      genotypic character of a tumor to be phenotypically masked (mimicry).

PMID- 14690183
TI  - Morphology of the vas deferens in an ethanol-drinking strain of rats (UChA and
      UChB).
AB  - Chronic alcoholism alters reproduction and therefore may be responsible for
      alterations of vas deferens, which are the subject of this analysis in UCh
      ethanol-drinking rats. The proximal and distal segments of the vas deferens of 20
      animals were submitted to macroscopic, light microscopy, electron microscopy and
      morphometric analysis. The UCh rats showed atrophy of the epithelium of the vas
      deferens and alterations of the hypothalamus-pituitary axis. Ethanol induces
      changes in the epithelium of the vas deferens and hypothalamus-pituitary axis of
      UCh rats.

PMID- 14690184
TI  - Variability of quantitative coronary angiography: an evaluation of on-site versus
      core laboratory analysis.
AB  - To assess the validity of locally performed off-line quantitative coronary
      angiography (QCA) measurement in clinical trials, we carried out a comparative
      study between on-site QCA analysis and analysis performed at an independent
      external core laboratory. One local operator analyzed the pre, post and follow-up
      angiograms of 116 patients participating in the Stenting in Small Coronary
      Arteries Study (SISCA) prior to final QCA analysis in the core laboratory. The
      mean values of the reference diameter (RD), minimal lumen diameter (MLD) and
      diameter stenosis (DS) showed acceptable agreement between study site and core
      laboratory. However, on the level of individuals the interobserver differences
      were large, affecting the outcome of restenosis rate significantly, and in a such
      way that the conclusions in the SISCA trial might have come out differently if a
      core laboratory had not been used. This emphasizes the importance of using
      independent core laboratories in coronary interventional trials.

PMID- 14690185
TI  - Evaluation of overall fibrinolytic activity in patients with coronary artery
      ectasia: global fibrinolytic capacity.
AB  - OBJECTIVE: Since the role of fibrinolytic activity is unclear in coronary artery
      ectasia, we investigated the entire fibrinolytic activity by a new test, global
      fibrinolytic capacity (GFC) in the ectasia patients. METHODS AND RESULTS: Thirty
      four ectasia patients (18 male, mean age: 58 +/- 8 years) presenting with acute
      coronary syndrome and 25 controls (14 male, mean age: 56 +/- 9 years) with normal
      coronary artery were evaluated. GFC, D-dimer and other hemostatic factors were
      assessed. Clinical characteristics were comparable in both groups. Serum GFC (4.6
      +/- 2.1 vs. 3.1 +/- 2.1 microg/ml, p = 0.03) and D-dimer levels (0.69 +/- 0.42
      vs. 0.41 +/- 0.38 ng/ml, p = 0.02, respectively) were significantly higher in
      ectasia patients than in controls. They were also higher in subgroup of patients
      with myocardial infarction (four patients) compared with other ectasia patients
      and controls (p = 0.04, 0.01, respectively). Other hemostatic factors were not
      different in both groups. GFC was correlated with D-dimer (r = 0.76, p = 0.01).
      CONCLUSION: Our results suggest that fibrinolytic system activation may develop
      in ectasia patients with acute coronary syndrome. It can be induced by thrombus
      formation in ectatic segment of coronary artery.

PMID- 14690186
TI  - Feasibility of continuous venous infusion of SonoVue for qualitative assessment
      of reversible coronary perfusion defects in stress myocardial contrast
      echocardiography.
AB  - OBJECTIVE: To study the feasibility of continuous intravenous SonoVue contrast
      echocardiography for qualitative assessment of reversible myocardial perfusion in
      dipyridamole stress tests. METHODS: Eleven patients (10 male and 1 female, mean
      age 66 years) with a history of chest pain and a clinical indication for stress
      sestamibi single photon emission computed tomography (SPECT) underwent concurrent
      SonoVue 99mTc myocardial contrast echocardiography (MCE). RESULTS: Of the total
      176 segments obtained, 53 (30%) were regarded as indeterminate, 39 (22%) as
      discordant, and 84 (48%) as concordant between MCE and SPECT imaging. Two
      patients had abnormal SPECT results. The overall feasibility and specificity of
      MCE were 70 and 74%, respectively. The concordant (p = 0.59) and discordant (p =
      0.55) segments were comparable with either MCE technique. However, continuous low
      mechanical-index imaging produced fewer indeterminate segments (17 segments, 32%)
      than intermittent harmonic B-mode imaging (36 segments, 68%) (p = 0.04).
      Significantly more indeterminate segments were found in the left anterior
      descending artery territory. However, the overall concordance was similar (p =
      0.5) in all three coronary artery territories. The concordance and discordance
      rates at different left ventricular levels (i.e., basal, mid, and apical) were
      similar (p = 0.50 and 0.08, respectively). CONCLUSION: Continuous-infusion
      SonoVue contrast echocardiography is feasible, with high specificity, for
      detecting myocardial perfusion defects as assessed by dipyridamole SPECT.

PMID- 14690187
TI  - Mutual information-based multimodality registration of cardiac ultrasound and
      SPECT images: a preliminary investigation.
AB  - BACKGROUND: Ultrasound (US) and single photon emission computed tomography
      (SPECT) are the two most commonly prescribed procedures for diagnosing coronary
      artery disease (CAD). We have demonstrated the feasibility of multimodality
      registration of two-dimensional (2D) and three-dimensional (3D) cardiac US images
      with cardiac SPECT images with an aim to simultaneously present the complementary
      anatomical and perfusion information from the two modalities. We have also tested
      the clinicians' assessment of the clinical adequacy of the registered images.
      METHODS AND RESULTS: We have demonstrated temporal and spatial registration for
      nine sets of cardiac US and SPECT cine loops covering the entire cardiac cycle.
      Temporal alignment was performed by interpolation of existing SPECT images at
      cardiac phases corresponding to available US images. Spatial registration was
      performed in 3D image space using a mutual information-based approach. Experts
      from echocardiography and nuclear medicine determined the clinical utility of the
      registration by rating each registration on a scale of 1 to 5, a rating of 3 or
      above indicating clinical utility. 2DUS-SPECT registration (five cases) received
      an average rating of 4.2, whereas 3DUS-SPECT registration (four cases) received
      an average rating of 2.85. By one-sample t test, the overall evaluations (mean
      3.58) were greater than the pre-specified clinical cut-off of 3 with p < 0.05,
      indicating likelihood of clinical utility. CONCLUSION: Our method demonstrates
      the feasibility of registering cardiac US and SPECT images in their present as
      well as possible future forms. Such registration has the potential to provide a
      more accurate and powerful tool for diagnosing CAD.

PMID- 14690188
TI  - Left atrial appendage aneurysm presenting with recurrent embolic strokes.
AB  - A case of left atrial appendage aneurysm is described in a 40-year-old man, who
      presented with recurrent embolic strokes and was asymptomatic until the last 6
      months. Chest X-ray revealed a slightly prominent upper left heart border. The
      diagnosis was made by transthoracic two-dimensional echocardiography and
      confirmed by transesophageal echocardiography, magnetic resonance imaging and
      also by surgery.

PMID- 14690189
TI  - Is I-123-beta-methyl-p-iodophenyl-methylpentadecanoic acid imaging useful to
      evaluate asymptomatic patients with hypertrophic cardiomyopathy? I-123 BMIPP
      imaging to evaluate asymptomatic hypertrophic cardiomyopathy.
AB  - PURPOSE: Myocardial imaging with I-123-beta-methyl-p-iodophenyl
      methylpentadecanoic acid (BMIPP) is useful for predicting the outcome of patients
      with hypertrophic cardiomyopathy (HCM). But its usefulness in asymptomatic
      patients is unclear. MATERIALS AND METHODS: Eighteen patients with asymptomatic
      HCM were examined with BMIPP and exercise stress perfusion imaging and then
      followed for 4.0 +/- 0.8 years. Extent of the defect (total defect score, TDS)
      and myocardial uptake of BMIPP (%uptake) were calculated to evaluate the BMIPP
      images. RESULTS: In the first study abnormal findings in the BMIPP and perfusion
      images were detected of 67 and 22% of the patients, respectively. In the second
      BMIPP study, the TDS had increased (2.1 +/- 2.7 to 4.1 +/- 4.9, p < 0.005) and
      the %uptake had decreased (5.67 +/- 0.88% to 4.81 +/- 0.91%, p < 0.001), but
      there were no differences in myocardial perfusion between the first and second
      study. Exertional dyspnea developed in 17% of the patients, and they were among
      the one third of the patients with the greatest reduction of %uptake. This group
      also showed deterioration of left ventricular (LV) %fractional shortening and LV
      volume in the second study. CONCLUSIONS: Abnormal findings on BMIPP images were
      frequently observed in patients with asymptomatic HCM, and these abnormal
      findings progressed with time. The greater reduction of %uptake during the follow
      up period reflects the deterioration of the LV function.

PMID- 14690190
TI  - Acute rest perfusion imaging in high risk unstable angina: association with
      troponin T and clinical endpoints.
AB  - BACKGROUND: Troponin T (TnT) and rest perfusion imaging (RPI) have been reported
      to be important diagnostic tools for risk stratification in patients with chest
      pain. METHODS: We investigated the association between two methods in 60 patients
      presenting with typical chest pain at rest within the last 6 h before admission.
      All patients underwent Tc-99m gated SPECT imaging and serial TnT measurements and
      were followed for occurrence of adverse cardiac events up to 30 days. RESULTS:
      Perfusion defect was detected in 42 patients and elevated TnT was observed in 23
      patients. All of the patients with an elevated TnT have also perfusion defect in
      RPI. Half of the patients with normal TnT level (51%) presented a perfusion
      defect detected by RPI (p = NS). The patients with elevated TnT levels had more
      perfusion defect numbers than those with normal TnT levels (8.2 +/- 2.9 vs. 5.3
      +/- 2.2; p = 0.0007). Cardiac events occurred in 38 patients (14 MI, 24
      revascularisation). In predicting cardiac events, RPI and TnT had sensitivities
      (97 vs. 58%; p < 0.001), specificities (77 vs. 95%, p = NS), positive predictive
      values (PPV) (88 vs. 96%; p = NS) and negative predictive values (NPV) (94% vs.
      57%; p = NS), respectively. In predicting MI, the two tests had sensitivities (93
      vs. 93%; p = NS), specificities (37 vs. 78%; p < 0.001), PPVs (31 vs. 57%; p =
      NS) and NPVs (94 vs. 97%; p = NS), respectively. CONCLUSIONS: These results
      suggest that in patients with rest angina (1) TnT elevation is associated with
      the extent of myocardial perfusion defect; (2) both tests are valuable, while
      positive RPI is more sensitive in predicting all cardiac events irrespective of
      TnT; both positive TnT and positive RPI predict a high probability to have MI;
      (3) both negative test results predict a very low probability to have cardiac
      event, including MI.

PMID- 14690191
TI  - Biphasic response to dobutamine predicts improvement of left ventricular
      dysfunction after revascularization: correlation with positron emission and rest
      redistribution 201Tl tomographies.
AB  - BACKGROUND: Dobutamine echocardiography (DSE), positron emission tomography (PET)
      and 201Tl-single photon emission computed tomography (SPECT) have been used to
      identify myocardial viability. There are few reports, however, that compare high
      doses DSE with myocardial metabolic and perfusion imaging techniques in the same
      patient population. The aim of this study was to determine the correlation
      between high doses DSE, metabolic PET and 201Tl-SPECT imaging to predict the
      recovery of function after revascularization in patients with severe left
      ventricular (LV) dysfunction. METHODS: Twenty-five patients underwent DSE (up to
      40 microg/kg/min), rest and 4-hour redistribution 201Tl SPECT, rest 13N-ammonia
      and 18fluoro-deoxy-glucose PET imaging and coronary angiography 7-10 days before
      surgical revascularization. A follow-up 2D-echocardiography was performed 6 weeks
      after surgery. RESULTS: Of the 109 successfully revascularized segments with
      severe dysfunction, 62 (57%) improved. LV ejection fraction increased from 30 +/-
      10% to 42 +/- 13 at follow-up (p < 0.05). 201Tl SPECT, PET and the presence of
      contractile reserve determined by DSE had a similar sensitivity (77-87%) to
      predict recovery of function, but specificity was higher for the PET mismatch
      pattern and biphasic DSE (85-89%) than for any of the 201Tl viability patterns
      (19-64%). The highest positive predictive values were obtained by biphasic DSE
      and PET mismatch pattern (78-79%) compared to all other criteria (54-67%). In a
      multivariate model, which included evidence of viability by all imaging
      modalities, biphasic response was the best predictor of regional recovery of
      function (Odds ratio, OR: 9.9, 95% confidence intervals, 95% CI: 3.5-27.8).
      CONCLUSIONS: Although DSE and PET had overall comparable results, the presence of
      contractile reserve by the biphasic response to dobutamine was a best predictor
      for the improvement of LV contractile function in this group of patients.

PMID- 14690192
TI  - Viability assessment: nuclear imaging vs. dobutamine echocardiography.

PMID- 14690193
TI  - A case of coronary artery fistula with mitral stenosis.
AB  - Coronary artery fistulae, being a rare form of congenital anomalies of the
      coronary arteries, are usually discovered by chance during coronary
      arteriography. However, these fistulae can cause an important coronary morbidity
      and mortality leading to angina, syncope, congestive heart failure, myocardial
      infarction and sudden death. The coincidence of mitral stenosis and congenital
      artery fistula is rare in the literature. In our case report, a patient with a
      coronary artery fistula originating from the circumflex, draining to the main
      pulmonary artery, discovered at cardiac catheterization and coronary angiography
      done with a prediagnosis of mitral stenosis is presented in the light of the
      literature.

PMID- 14690194
TI  - Arrhythmogenic right ventricular cardiomyopathy: diagnostic and prognostic value
      of the cardiac MRI in relation to arrhythmia-free survival.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a potentially fatal
      disease, which is often difficult to diagnose. As a non-invasive test cardiac
      magnetic resonance imaging (CMR) has become an important tool in establishing the
      diagnosis. The aim of this study was to evaluate the diagnostic and prognostic
      value of CMR in patients with suspected ARVC and to assess the long-term outcome
      of patients with CMR-diagnosed ARVC. Thirty-six patients with suspected ARVC (26
      male, 10 female, median age 41 years) underwent non-invasive and invasive
      clinical tests as gold standard for ARVC diagnosis. ARVC was clinically diagnosed
      in 19 patients and excluded in 17 patients. Both groups underwent CMR, and
      diagnosis was confirmed by CMR in 16/18 patients with clinically diagnosed ARVC
      (sensitivity 89%), and correctly excluded in 14/17 of patients with clinically
      excluded ARVC (specificity 82%). This result indicates a positive predictive
      value of the CMR of 84%, and a negative predictive value of 88%, respectively (p
      < 0.0001). Using a scoring system, multiple CMR parameters were compared in the
      two groups in regard of the clinical diagnosis. By univariate analysis, right
      ventricular fatty tissue infiltration (p = 0.0003) was predictive for diagnosis.
      Compared by outcome, 37% of patients with clinically and by CMR-diagnosed ARVC
      had an arrhythmic event during a mean follow-up of 16 +/- 11 months. These data
      suggest that CMR is a highly sensitive and specific method to diagnose or exclude
      ARVC, and thus, has an important prognostic impact on predicting arrhythmia free
      survival.

PMID- 14690195
TI  - MR imaging in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

PMID- 14690196
TI  - FDA guidance on antimicrobials aims to prevent resistance.

PMID- 14690197
TI  - Wildfires pack a wallop.

PMID- 14690198
TI  - OIE: too few countries follow international BSE guidelines.

PMID- 14690199
TI  - More feedback on taurine deficiencies in cats, dogs.

PMID- 14690200
TI  - Additional input on feral cat debate.

PMID- 14690201
TI  - What is your diagnosis? Transitional cell carcinoma.

PMID- 14690202
TI  - ECG of the month. Second degree atrioventricular (AV) block.

PMID- 14690203
TI  - Rabies surveillance in the United States during 2002.
AB  - During 2002, 49 states and Puerto Rico reported 7,967 cases of rabies in nonhuman
      animals and 3 cases in human beings to the Centers for Disease Control and
      Prevention, an increase of 7.2% from the 7,436 cases in non-human animals and 1
      case in a human being reported in 2001. More than 92% (7,375 cases) were in wild
      animals, whereas 7.4% (592) were in domestic species (compared with 93.3% in wild
      animals and 6.7% in domestic species in 2001). Compared with cases reported in
      2001, the numbers of cases reported in 2002 increased among all major reporting
      groups with the exception of swine and rodents and lagomorphs. The relative
      contributions of the major groups of animals were as follows: raccoons (36.3%;
      2,891 cases), skunks (30.5%; 2,433), bats (17.2%; 1,373), foxes (6.4%; 508), cats
      (3.8%; 299), dogs (1.2%; 99), and cattle (1.5%; 116). Thirteen of the 19 states
      in which the raccoon-associated variant of the rabies virus has been enzootic
      reported increases in the numbers of rabid raccoons during 2002. Among those
      states that have engaged in wildlife rabies control programs, Ohio reported 1
      case of raccoon rabies associated with the epizootic of rabies in raccoons and 1
      case in an equid that was infected with a bat variant of the rabies virus,
      compared with 2 cases reported in terrestrial animals during 2001. Texas reported
      no cases of rabies associated with the dog/coyote variant of the rabies virus
      (compared with 1 case in 2001) and 65 cases associated with the gray fox variant
      of the virus (an increase of 225% from 20 cases reported in 2001). In
      Massachusetts and Rhode Island, states with enzootic raccoon rabies, reports of
      rabid skunks again exceeded those of rabid raccoons (the sixth consecutive year,
      although in Rhode Island, this difference decreased to only 7 more skunks than
      raccoons [38/31]). Tennessee reported a single case of raccoon rabies in a pet
      raccoon from the central part of the state; the captive animal had been
      transported toTennessee from northern Georgia. Nationally, the number of rabies
      cases in skunks during 2002 increased by 6.6% over those reported in 2001. Texas
      reported the greatest number (740) of rabid skunks and the greatest overall state
      total of rabies cases (1,049) during 2002. The 1,373 cases of rabies reported in
      bats during 2002 surpassed the previous year's record (1,281 cases) as the
      largest number of reported cases ever recorded for this group of mammals. Cases
      of rabies reported in cats (299), cattle (116), and dogs (99) increased by 10.7%,
      41.5%, and 11.24%, respectively, from 2001 to 2002. Rabies among sheep and goats
      increased 400% from 3 cases in 2001 to 15 in 2002, and cases among horses and
      mules increased 13.7% (51 cases in 2001 to 58 in 2002). Reported cases of rabies
      in mongooses in Puerto Rico decreased 4.3% from the previous year (70 cases in
      2001 to 67 cases in 2002), while cases of rabies in dogs increased 77% (13 to
      14). California, Tennessee, and Iowa each reported a case of rabies in a human
      being during 2002. All cases of rabies in humans were the result of infection
      with bat variants of the rabies virus.

PMID- 14690204
TI  - Ehrlichiosis and related infections.

PMID- 14690205
TI  - Economic consequences of control programs for paratuberculosis in midsize dairy
      farms in the United States.
AB  - OBJECTIVE: To evaluate the epidemiologic efficacy and economic efficiency of
      current and potential future control programs for paratuberculosis (Johne's
      disease) on midsize dairy herds in the United States. DESIGN: Stochastic dynamic
      computer simulation model. SAMPLE POPULATION: Data on prices and other input
      variables collected from various sources were used to represent a population of
      midsize US dairy herds infected with paratuberculosis. PROCEDURE: The simulation
      model was modified to reflect management and production characteristics of
      midsize dairy herds in the United States. The model was validated by use of field
      data and expert opinion. Various control strategies then were simulated and
      compared on an epidemiologic basis and on the basis of economic efficiency.
      RESULTS: Test-and-cull strategies and vaccination against paratuberculosis were
      not able to decrease the mean prevalence of disease in the United States.
      Typically, only vaccination was economically attractive. Improved management
      strategies decreased the prevalence of paratuberculosis considerably and had high
      economic benefits. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results of
      this study suggests that test-and-cull strategies alone do not reduce the
      prevalence of paratuberculosis in cattle and are costly for producers to pursue.
      Vaccination did not reduce the prevalence but was economically attractive.
      Finally, improved calf-hygiene strategies were found to be critically important
      in every paratuberculosis control program and most were economically attractive
      programs for midsize US dairy farms with the disease.

PMID- 14690206
TI  - Glomerulocystic kidney disease in a kitten.
AB  - A 4-month-old 1-kg female Siamese-Manx cross kitten was evaluated because of
      renomegaly and renal failure. Ultrasonography and cytologic examination of a
      renal aspirate failed to provide an antemortem diagnosis. Histologic lesions
      included diffuse cystic dilatation of all tubules and Bowman's spaces in the
      renal cortex and occasional small glomerular tufts; the lesions were similar to
      those of glomerulocystic kidney disease of humans. Glomerulocystic kidney disease
      is a rare cause of early-onset renal failure, but should be considered when
      renomegaly is detected, cysts are not detected in the kidney by ultrasonography,
      and cytologic examination of a renal aspirate is nondiagnostic.

PMID- 14690207
TI  - Lobar holoprosencephaly in a Miniature Schnauzer with hypodipsic hypernatremia.
AB  - A 9-month-old male Miniature Schnauzer was examined because of a lifelong history
      of behavioral abnormalities, including hypodipsia. Diagnostic evaluation revealed
      marked hypernatremia and a single forebrain ventricle. The behavioral
      abnormalities did not resolve with correction of the hypernatremia, and the dog
      was euthanatized. At necropsy, midline forebrain structures were absent or
      reduced in size, and normally paired forebrain structures were incompletely
      separated. Findings were diagnostic for holoprosencephaly, a potentially genetic
      disorder and the likely cause of the hypodipsia. Similar evaluation of affected
      Miniature Schnauzer dogs may reveal whether holoprosencephaly routinely underlies
      the thirst deficiency that may be seen in dogs of this breed.

PMID- 14690208
TI  - Risk factors and prevalence of injuries in horses during various types of
      steeplechase races.
AB  - OBJECTIVE: To identify the types of injuries sustained by horses that competed in
      steeplechase races and determine the prevalence of and risk factors for those
      injuries. DESIGN: Prospective study. ANIMALS: 2,680 horses that competed in
      various types of steeplechase races from 1996 through 2000. PROCEDURE: Data
      regarding races; environment; equipment problems; the number of horses that
      entered, started, and finished races; the number of riders that fell; and the
      number of horses that were slowed or stopped by the rider, ran off the course,
      fell, and sustained injuries or physical abnormalities during races were
      collected on a standard form by the official veterinarian who attended each meet.
      Data from all meets were not recorded; however, in recorded meets, data from
      every race were reported. RESULTS: Data for 197 hurdle, 65 timber, 76 flat, and 8
      mixed races were recorded. Nine (3.4/1,000 horses that started in races) horses
      died or were euthanatized, and 7 of those were associated with catastrophic
      musculoskeletal injury. Seven fractures were recorded. Four fractures involved
      forelimbs, 1 involved a hind limb, and 2 involved the cervical portion of the
      vertebral column. All horses with fractures were euthanatized. Deep or hard
      course conditions were associated with an increased risk of breakdown injuries.
      CONCLUSIONS AND CLINICAL RELEVANCE: Successful development and implementation of
      strategies to prevent injuries and death in horses in steeplechase races depend
      on a clear understanding of the types and prevalence of injuries involved and
      risk factors associated with those injuries.

PMID- 14690209
TI  - Foal-related risk factors associated with development of Rhodococcus equi
      pneumonia on farms with endemic infection.
AB  - OBJECTIVE: To identify foal-related risk factors associated with development of
      Rhodococcus equi pneumonia among foals on farms with endemic R. equi infection.
      DESIGN: Prospective case-control study. ANIMALS: 220 foals at 2 equine breeding
      farms in Texas during a 2-year period. PROCEDURE: Information collected for each
      dam included age, time housed on the farm prior to parturition, whether there
      were any peripartum illnesses, parity, and health of previous foals. Information
      collected for each foal included breed, sex, gestational age, month and year of
      birth, location of birth, type of flooring and bedding in stall, postpartum
      management and preventive health care, passive immunity status, supplementation
      of immunoglobulins, exposure to other farms or foals affected with R. equi
      pneumonia, stall and pasture exposure, commingling with other mare-foal pairs,
      age at weaning, and whether the foal developed R. equi pneumonia. RESULTS: 32 of
      the 220 (15%) foals developed R. equi pneumonia, of which 4 (13%) died. Foals at
      1 of the 2 farms and foals born during the second year of the study were more
      likely to develop R. equi pneumonia. Foal-related factors that were examined were
      not significantly associated with risk of R. equi pneumonia in multivariate
      analyses. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that there are farm
      and year-related effects on the risk that foals will develop R. equi pneumonia.
      Other foal-related factors significantly associated with R. equi pneumonia were
      not identified.

PMID- 14690210
TI  - Use of a three-drill-tract technique for arthrodesis of the distal tarsal joints
      in horses with distal tarsal osteoarthritis: 54 cases (1990-1999).
AB  - OBJECTIVE: To assess the long-term clinical outcome of horses with distal tarsal
      osteoarthritis (OA) in which a 3-drill-tract technique was used to induce
      arthrodesis of the affected joints, identify any preoperative or operative
      factors associated with outcome, and describe any complications associated with
      the technique. DESIGN: Retrospective study. ANIMALS: 54 horses. PROCEDURE:
      Medical records were reviewed for information on signalment, use, history,
      physical and lameness examination findings, surgical technique, and postoperative
      care. Radiographs were examined, and severity of OA was graded. Follow-up
      information was obtained through telephone interviews with owners at least 13
      months after the procedure. RESULTS: 32 (59%) horses had a successful outcome, 6
      (11%) improved but were not sound after surgery, and 16 (30%) did not improve
      following surgery. Outcome was negatively associated with the previous use of
      intra-articular injections. Few postoperative complications were evident.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that distal tarsal OA in
      horses can be successfully treated by means of distal tarsal arthrodesis with a 3
      drill-tract technique. Horses with advanced distal tarsal OA are likely to have
      poorer outcomes, and the procedure will likely be of minimal benefit in horses
      with concomitant causes of hind limb lameness prior to surgery and in horses with
      preexisting proximal intertarsal joint disease.

PMID- 14690211
TI  - Potential pathogens in feces from unweaned llamas and alpacas with diarrhea.
AB  - OBJECTIVE: To identify potential pathogens in feces from llama and alpaca crias
      with diarrhea. DESIGN: Prospective observational study. ANIMALS: 45 unweaned
      crias with diarrhea. PROCEDURE: Fecal samples were evaluated for Eimeria spp,
      Giardia spp, Cryptosporidium spp, enteric viruses, and Salmonella spp. A
      questionnaire yielded information concerning herd management and presence of
      other affected camelids. RESULTS: 28 crias were < or = 31 days old, 11 were 32 to
      62 days old, and 6 were 63 to 210 days old. Potential pathogens were isolated
      from feces from 32 of the 45 crias. A total of 39 potential pathogens were
      obtained, including coronavirus (n = 19 crias; 42%), Giardia spp (8; 18%),
      Eimeria spp (6; 13%), Cryptosporidium spp (4; 9%), rotavirus (1; 2%), and
      nematode ova (1; 2%). Salmonella spp were not isolated. Most crias from which
      potential pathogens were isolated were identified during outbreaks of diarrhea
      involving other camelids, although only coronavirus was isolated from crias
      identified during outbreaks involving adult camelids. Coronavirus was detected
      throughout the year, whereas protozoa were most commonly isolated during the fall
      and winter. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that a variety of
      potential pathogens may be isolated from young crias with diarrhea. Many crias
      shed coronavirus, which may also have been affecting older camelids. Protozoa
      were isolated most often during wetter months, suggesting that crias born during
      these months may have greater exposure to protozoal pathogens.

PMID- 14690213
TI  - Asymmetric synthesis in a Norrish type II cleavage reaction induced by crystal
      chirality.
AB  - Moderate to high enantiomeric excesses for the cis and trans olefinic products of
      a Norrish type II cleavage reaction have been obtained for the first time through
      the use of the solid-state ionic chiral auxiliary approach.

PMID- 14690212
TI  - Dermatophytosis in three colony-born spotted hyenas.
AB  - An adult female hyena and her two 4-month-old cubs were found to have multifocal
      areas of alopecia and dermatitis. Dermatophyte culture of hair and skin samples
      collected from the lesions yielded Trichophyton mentagrophytes. None of 10 other
      animals in the colony that were tested were found to have dermatophytes. Lesions
      were treated twice, at 3-week intervals, with thorough cleansing with
      chlorhexidine scrub followed by topical application of antifungal agents. Lesions
      resolved, and dermatophyte culture of samples collected 6 weeks after the
      initiation of treatment did not yield growth.

PMID- 14690214
TI  - Enhancement effect of Mg(ClO4)2 on TiO2-catalyzed photooxygenation of 1,2
      diarylcyclopropanes.
AB  - The TiO2-catalyzed photooxygenation of electron-rich 1,2-diarylcyclopropanes via
      electron transfer in acetonitrile is significantly accelerated by the addition of
      Mg(ClO4)2.

PMID- 14690215
TI  - Conformer-specific photoisomerizaton of some 2-vinylbiphenyls.
AB  - The ground-state conformations, spectroscopy, and photochemistry of 2
      vinylbiphenyl and three of its vinylsubstituted derivatives have been
      investigated. The ground state exists as a mixture of syn and anti conformers in
      which the vinyl group is directed either toward or away from the unsubstituted
      phenyl ring. Both conformers are highly non-planarn having large phenyl phenyl
      and phenyl vinyl dihedral angles. The vinylbiphenyls are found to undergo
      conformer-specific photochemistry. The syn rotamers are non-fluorescent and
      undergo rapid and efficient cyclization to 8a,9-dihydrophenanthrene
      intermediates, which undergo rapid thermal sigmatropic rearrangements to yield
      9,10-dihydrophenanthrenes. The intermediates have been generated at 77 K and
      detected by absorption spectroscopy. The singlet states of the anti rotamers are
      fluorescent, and undergo competing intersystem crossing and activated C=C
      torsion. The torsional barriers are of the order of those for styrenes with
      similar vinyl substituents.

PMID- 14690216
TI  - A topologically new ruthenium porphyrin-fullerene donor-acceptor ensemble.
AB  - A novel ruthenium porphyrin complex bearing an axially coordinated fullerene
      ligand (RuP-C60), that is, a fulleropyrrolidine that bears a pyridine moiety, was
      developed as an artificial reaction center mimic. Generally, the new donor
      acceptor dyad gives rise to rapid intramolecular deactivation of the ruthenium
      porphyrin triplet excited state, which evolves from instantaneous intersystem
      crossing. The product of the ruthenium porphyrin excited-state deactivation
      depends on the solvent polarity. While in non-polar solvents a transduction of
      triplet excited energy predominates, in medium and strongly polar media, charge
      separation leads to the formation of RuP*+ C60*-.

PMID- 14690217
TI  - Laser flash photolysis of bismaleimides.
AB  - Bismaleimides containing between 2 and 12 methylene spacer units have been
      synthesized and characterized using laser flash photolysis spectroscopy. In the
      case of the monofunctional N-methylmaleimide, the 1,4-biradical was observed only
      at maleimide concentrations high enough to effectively quench the triplet state,
      indicating that the 1,4-biradical is Formed from self-quenching of the triplet
      excited state. The transient spectral features and the transient lifetimes of
      bismaleimides containing 2 and 9 methylene spacer units closely resemble those of
      N-methylmaleimide and are attributed to triplet-state transients. N,N'
      Alkylenebismaleimides with 3 and 6 methylene spacer groups exhibit a transient
      with a very short lifetime attributed to a singlet 1,4-biradical species formed
      from intramolecular interaction. The absence of triplet spectra in these latter
      bismaleimides indicate that the 1,4-biradical is formed directly from the excited
      singlet state. The large difference in the lifetime of the 1,4-biradical formed
      in monofunctional maleimide solutions and bismaleimide solutions is reflective of
      differences in the biradical spin-state multiplicity. The bismaleimide with a 12
      methylene spacer group exhibits transient spectra corresponding to both a triplet
      state of the maleimide and a 1,4-biradical formed by exo interaction of two
      maleimide groups. As a demonstration of the ability of acrylate monomers to react
      with the short-lived singlet biradicals, it is shown that the photopolymerization
      of a multifunctional acrylate monomer is readily initiated by the 1,4-biradical
      formed from the bismaleimides with 3 and 6 methylene spacer groups, presumably by
      direct reaction of the biradical with the acrylate.

PMID- 14690219
TI  - Photochromism of diarylethenes in nanolayers of a single crystal.
AB  - 1,2-Bis(2-methyl-5-pentafluorophenyl-3-thienyl)perfluorocyclopentene (1a) and 1,2
      bis(2-ethyl-5-phenyl-3-thienyl)-perfluorocyclopentene (2a) were found to form a
      1:1 stoichiometric co-crystal. The crystal is composed of alternate nanolayers of
      1a and 2a molecular sheets. pi-pi Stacking of 1a and 2a molecules by aryl
      perfluoroaryl interactions was not discerned. One-component 1a and 2a crystals
      and the co-crystal showed a reversible colour change from colourless to blue upon
      irradiation with ultraviolet and visible light. Although both 1a and 2a molecules
      underwent efficient photochromic reactions in the one-component crystals upon
      photoirradiation, only 2a underwent the reaction up to a conversion of 20% in the
      co-crystal, as confirmed by HPLC and X-ray crystallography. This indicates that
      excited energy transfer occurs from 1a to 2a in the crystal.

PMID- 14690218
TI  - Photoinduced electron transfer in alpha-helical polypeptides: dependence on
      conformation and electron donor-acceptor distance.
AB  - Long distance electron transfer in proteins is a multiple-pathway process whose
      kinetics is modulated by the dynamics of flexible peptide chains. Such complexity
      can be observed even in relatively simple systems, eg. donor bridge acceptor,
      where the bridge is a polypeptide alpha-helix. We have investigated a series of
      24-residue helical polypeptides that exist as monomers in water alcohol media.
      The principal chromophore and electron acceptor, a pyrene moiety, is connected to
      the N-terminus via a flexible linker. The electron donor, a tryptophan residue,
      was placed various distances away from the pyrene-labeled terminus. Time-resolved
      emission spectroscopy, associated with the fluorescent pendant, pyrene, was
      employed to study the photoinduced electron-transfer kinetics for the polypeptide
      analogs. Mechanisms involving only through-bond pathways could not account for
      the pattern of measured fast charge-separation rates. When the electron donor was
      placed far enough from the acceptor (i.e. at least six residues apart), a
      decrease in the electron-transfer rates with the donor acceptor distance was
      observed. The emission decays for polypeptides with the electron donor exhibited
      complex behavior and could not be fit using a single-exponential function. For
      the treatment of the time-resolved data, a multi-exponential model was developed
      that is based on the assumption of a Gaussian distribution of the classical
      electronic coupling beta values among the conformers responsible for the observed
      electron-transfer processes. This approach proved to be informative because, in
      addition to the mean values of the electron-transfer rate constants, the widths
      of the distributions of these rates illustrate the size of the conformational
      space explored by the flexible chains that provide pathways for electron
      transfer.

PMID- 14690220
TI  - In situ EPR investigation of the addition of persistent benzyl radicals to
      acrylates on ZSM-5 zeolites. Direct spectroscopic detection of the initial steps
      in a supramolecular photopolymerization.
AB  - Photolysis of dibenzyl ketone derivatives adsorbed on ZSM-5 zeolites produces
      persistent benzyl radicals (initiator radicals), which add to methyl acrylates
      (monomers) to generate persistent adduct radicals. Both initiator and adduct
      radicals are readily observable by conventional steady-state EPR spectroscopy at
      room temperature and are persistent for time periods ranging from seconds to many
      days. The rate of the formation and the amount of the adduct persistent radical
      formed depends on the structure of the initiator radical (benzyl radical
      derivative) and the structure of the monomer (acrylate derivative). The lifetimes
      of the initiator and adduct radicals depend on the supramolecular structure of
      the radical@zeolite complex and the diffusion and reaction dynamics of the
      radicals in the complex. The most intense signal and highest addition rate to
      methyl acrylate were observed for the smallest initiator radical, the benzyl
      radical, because of its high mobility and relatively rapid diffusion within the
      internal zeolite surface. With increasing length of an alkyl chain (methyl,
      ethyl, and pentyl) on either the initiator (alpha position of the radical) or
      monomer (alkyl group of acrylate ester), the rate of radical addition to the
      monomer decreased, a result that is consistent with the decreased mobility and
      diffusion of the initiator radical or monomer. Deuterium isotope experiments and
      variation of the methyl acrylate concentration demonstrated that the initial
      adduct radical from methyl acrylate adds to another methyl acrylate to generate a
      secondary adduct radical, which, in turn, can continue to propagate to form a
      polymer that is cross-linked to the zeolite crystals. The results demonstrate
      that EPR can be a powerful tool for the direct in situ analysis of supramolecular
      photochemistry involving radicals rendered persistent by supramolecular steric
      effects. The latter eliminate the need for sophisticated flash photolysis
      equipment to investigate the structure and dynamics of reactive radicals and
      require only the use of simpler steady-state lamps.

PMID- 14690221
TI  - Photoisomerization of 2,3-diphenylcyclopropane-1-carboxylic acid derivatives.
AB  - Contrary to what is known about cis-1,2-diphenylcyclopropane and its derivatives,
      we find that they have triplet energies of ca. 311 kJ mol(-1), do not undergo
      intersystem crossing upon direct excitation, undergo the less common adiabatic
      photoisomerization to the corresponding trans isomers, and show emission from
      excited 1,3-diradical intermediates.

PMID- 14690222
TI  - Fluorescence kinetics of aqueous solutions of tetracycline and its complexes with
      Mg2+ and Ca2+.
AB  - The fluorescence spectra of acidified aqueous solutions of tetracycline (tcH3+)
      exhibit three components with slightly different degrees of anisotropy: the
      'blue' component (lambdad approximately equal to 475 nm) decays on the timescale
      of a few picoseconds; the second, most intense component (lambdad approximately
      equal to 530 nm) shows decay times of about 25 (H3O+) and 70 ps (D3O+); the third
      component (lambdad approximately equal to 650 nm) is longer lived (tau
      approximately equal to 200 ps). All three fluorescence components appear quasi
      instantaneously, thus providing evidence that the relaxation processes which give
      rise to the unusually large Stokes shifts occur on a (sub-)picosecond timescale.
      The effect of H/D exchange suggests that these relaxation processes involve
      excited-state intramolecular proton transfer (ESIPT) of OH10 and/or OH12, but
      does not exclude a change in the hydrogen-bonding pattern to the solvent
      molecules. The low overall fluorescence yield of the fully protonated form must
      be correlated to the presence of a very fast decaying species. In alkaline
      aqueous solution, the fluorescence of the dianion (tc2-) essentially comprises
      two components; the decay time of the stronger, shorter-lived component is about
      30 ps, that of the weaker, longer-lived one about 160 ps. The relative amplitude
      of the latter is larger at pH 11 than at pH 8.5, in accordance with the increase
      in the steady-state fluorescence intensity upon increasing the pH from 8.5 to 11.
      Complexation of the dianion with divalent metal ions like Mg2+ or Ca2+ leads to a
      strong enhancement of the steady-state fluorescence. In the time-resolved
      spectra, the decay time of the major fluorescence component exhibits
      approximately a five-fold increase in comparison to the major component of the
      dianion. It is about 150 ps in both types of complexes. The decay times of the
      minor component are increased to about 500 (Mg2+) and 320 ps (Ca2+). The absence
      of the ultra-fast component in the fluorescence of the dianion and its metal
      complexes provides evidence that a reaction of OH 12 must be responsible for the
      ultra-fast fluorescence component in tcH3+. The existence of a component with a
      lifetime of several tens of picoseconds in all samples suggests the involvement
      of hydrogen bonding at OH10 during the formation of the emitting species. DFT
      calculations for the isolated molecule provide evidence that ESIPT is indeed an
      energetically allowed relaxation process for those isomers that have only one
      intramolecular hydrogen bond to O11. The ESIPT process yields primary
      photoproducts that should emit at much longer wavelengths, thereby explaining the
      unusually large fluorescence Stokes shift.

PMID- 14690223
TI  - Generation dependent singlet-singlet annihilation within multichromophoric
      dendrimers studied by polychromatic transient absorption.
AB  - Intramolecular kinetic processes in a series of shape-persistent meta- and para
      substituted polyphenylene dendrimers bearing different peryleneimide chromophores
      at the rim have been investigated using time-resolved polychromatic transient
      absorption measurements. The influence of the generation number and different
      substitution patterns upon these processes was revealed by comparing different
      compounds. In particular, in multichromophoric systems a singlet-singlet
      annihilation process was detected. The corresponding time constant was dependent
      on the generation number.

PMID- 14690224
TI  - Monitoring photodecomposition of dibenzyl ketone within NaY zeolite with a pre
      fluorescent nitroxide compound.
AB  - Benzyl radicals derived from photodecomposition of dibenzyl ketone have been
      monitored in NaY zeolite using the pre-fluorescent probe 4-(3-hydroxy-2-methyl-4
      quinolinoyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl free radical (QT). The
      steady-state and time-resolved fluorescence show a strong interaction of QT
      within the zeolite cavities. Furthermore, the increase in the fluorescence with
      the irradiation time reveals the efficient trapping of benzyl radicals by QT
      under vacuum. Dispersion of the zeolite composites in liquid polymers results in
      an improvement in the fluorescence measurement and faster kinetics in comparison
      with the solid samples. These results are interpreted in terms of partial
      refractive index matching as a consequence of polymer reptation into the zeolite
      cavities. Analysis of the fluorescence lifetime distribution shows the presence
      of different fluorescence ensembles with different fluorescence quantum yields,
      depending on the microenvironment within the zeolite particle. Pre-fluorescent
      probes offer a novel and useful methodology for studying radical processes in
      zeolites.

PMID- 14690225
TI  - Photofragmentation of C,N-protected alpha-amino acids: comparing tert-leucine
      with sulfur-containing amino acids methionine and cysteine.
AB  - The photochemical fingerprint for the N-acetyl methyl ester of the aliphatic
      amino acid tert-leucine 1 was investigated. This reaction path was compared with
      the electron transfer active amino acids methionine (N-acetyl methyl ester
      derivative 2a as well as the methyl ester derivative 2b) and the cysteine
      derivatives 3a and 3b (penicillamine derivative). Photofragmenation of the ester
      group dominated the photolysis of 1, whereas loss of methylmercaptane was
      observed for 2a and 3a. Vinylglycine derivatives 11 and 14 were formed to a minor
      extent. The gem-dimethylated compound 3b gave a solvent-characteristic product
      pattern with photoelimination products 18 and 19 in acetonitrile and loss of
      methylmercaptane to give 20 in methanol.

PMID- 14690226
TI  - Decay pathways of charge-separated states in strongly fluorescent electron donor
      acceptor compounds.
AB  - The nonradiative decay pathways are studied of the 1-cyano-4
      cyclohexylidenenaphthalene chromophore and electron donor acceptor compounds
      containing the same chromophore. It is argued that the rapid decay at room
      temperature of the locally excited singlet state of the electron acceptor
      chromophore involves twisting of the double bond via a low barrier, and a polar
      transition state. In non-polar solvents the charge transfer excited states also
      decay mostly via a thermally activated decay process, possibly via a similar
      pathway as the locally excited state of the acceptor unit. In more polar
      solvents, decay via direct charge recombination to the ground state obeys the
      energy gap law, but in contrast to the prediction of semiclassical Marcus theory
      an activation energy of 1-2 kcal mol(-1) is found.

PMID- 14690227
TI  - Probing the binding dynamics to sodium cholate aggregates using naphthalene
      derivatives as guests.
AB  - The binding dynamics with bile salt aggregates for a series of naphthalene
      derivatives of different polarities was studied using fluorescence and laser
      flash photolysis. Fluorescence was employed to determine the nature of the
      binding site for each guest and the accessibility of the bound guest to
      quenchers. Laser flash photolysis was employed to study the mobility of the
      triplet states of the naphthalenes between the sodium cholate aggregates and the
      aqueous phase. Primary aggregates, which provide an environment protected from
      quenchers in the aqueous phase, bind 1- and 2-ethylnaphthalene as guests. The
      complexation dynamics with this type of aggregate is slow. 1- and 2-Naphthyl-1
      ethanol, and 1- and 2-acetonaphthone bind to the secondary aggregates, which
      provide moderate protection from quenching and faster binding dynamics. The
      addition of salts lowered the cholate concentration at which primary aggregates
      were formed, but did not influence the formation of secondary aggregates.

PMID- 14690228
TI  - Supramolecular control of [2 + 2] photodimerization via hydrogen bonding.
AB  - The use of supramolecular catalysis to control the photoinduced dimerization of
      styrene, cinnamate, and stilbene chromophores is reported. The strategy employs
      the formation of a 2:1 supramolecular assembly in the presence of 5,5
      dihexylbarbituric acid (DHB). A 3- to 10-fold increase in dimerization efficiency
      is observed in its presence, concomitant with accrued selectivity for the syn
      photodimers. The origin of the regioselectivity in the presence of DHB is
      discussed in terms of topochemical control within the supramolecular
      architecture.

PMID- 14690229
TI  - The effect of solvent polarizability on the fluorescence of trans-1-(2-naphthyl)
      2-phenylethene conformers. Conformer-specific fluorescence from the cis isomer.
AB  - A matrix of trans-1-(2-naphthyl)-1-phenylethene (t-NPE) fluorescence spectra
      obtained from benzene solutions at 20 degrees C by varying the excitation
      wavelength (lambdaexc) and the oxygen concentration is resolved into pure
      conformer fluorescence spectra by use of principal component analysis with self
      modeling based on optimum global Stern Volmer constant criteria. The resulting
      fractional contributions of the two components to the fluorescence spectra are
      combined with observed fluorescence quantum yields as a function of lambdaexc to
      obtain the conformer-specific quantum yields. These quantum yields and
      fluorescence lifetimes are used to determine conformer-specific radiative and
      radiationless rate constants. Comparison with results from an analogous study in
      methylcyclohexane reveals pronounced, diferential enhancements of all these rate
      constants in benzene (Bz). Preliminary measurements of emission from a cis-1-(2
      naphthyl)-1-phenylethene (c-NPE) solution in Bz at 20 degrees C, under static
      cell conditions, are dominated by sequential two-photon-induced t-NPE
      fluorescence due to excitation of t-NPE formed photochemically from the cis
      isomer. The spectra also reveal a weak structureless broad emission, which is
      assigned to 1c-NPE* by comparison with the published low temperature fluorescence
      spectrum of c-NPE in a hydrocarbon glass. The conformational origin of this
      emission is addressed.

PMID- 14690230
TI  - Associative return electron transfer. A bond-coupled electron transfer in the
      photoreactions of cyclopropylamines.
AB  - The dynamics of the geminate radical-ion pairs formed by electron transfer to the
      excited states of cyanoanthracenes from 2-phenylcyclopropylamines are dominated
      by exothermic bond cleavage of the amine radical cations. Quantitative studies of
      product formation as a function of the energetics of the photochemical and
      corresponding thermal reactions provide support for a novel mechanism in which
      return electron transfer in the geminate pair occurs in concert with bond
      formation from the ring-opened radical cations. This bond-coupled electron
      transfer process is referred to as an associative return electron transfer
      reaction. The important features of the associative electron transfer process
      that explain the experimental observations are described in terms of potential
      energy surfaces and competition between adiabatic and non-adiabatic deactivation
      paths.

PMID- 14690231
TI  - The influence of core size on electronic coupling in shell-core nanoparticles:
      gold clusters capped with pyrenoxylalkylthiolate.
AB  - The mean size of the metallic core of monolayer-protected gold clusters densely
      capped with 9-(1-pyrenoxyl)octane-1-thiol or 1-dodecanethiol can be adjusted by
      controlling the thiol/HAuCl4 ratio during synthesis. Upon reduction of
      tetrachloroaurate by NaBH4, lower mean metal core diameters were attained in
      those composites prepared from mixtures with higher thiol/Au ratios. The
      efficiency of electronic coupling between the core metal cluster and pyrenyl
      groups appended as an outer shell in this size-graded family was studied by
      absorption and fluorescence spectroscopy. The observed emission intensity from
      the bound fluorophores is independent of the gold core size.

PMID- 14690232
TI  - Photoisomerisation and fluorescence behaviour of polyphenylene-based stilbene
      dendrimers.
AB  - The photoinduced structural changes of three polyphenylene-based stilbene
      dendrimers, G1, G2, and G3, has been studied. They all exhibit fluorescence
      emission with considerably higher quantum efficiency and longer fluorescence
      lifetimes compared with the parent stilbene. These dendrimers undergo mutual cis 
      -> trans isomerisation on direct irradiation with 310 nm light at room
      temperature. In a solvent glass at 77 K, one-way cis --> trans isomerisation was
      observed for G2. A volume-conserving isomerisation mechanism is presumed to be
      operating in the cis-to-trans isomerisation of G2 at 77 K.

PMID- 14690233
TI  - Acid-controlled photoreactions of aryl alkanoates: competition of
      transesterification, decarboxylation, Fries-rearrangement and/or transposition.
AB  - 2,4,6-Trimethylphenyl (mesityl) cyclohexanecarboxylate 1c and related mesityl
      esters 1a,b and d-f were photodecarboxylated upon irradiation at 254 nm in
      neutral solvents to give alkylmesitylenes 15 in good yields. In contrast, in the
      presence of a catalytic amount of acid and a sufficient amount of alcohol, the
      same compounds underwent facile phototransesterification to afford the
      corresponding ester 9 and phenol 10 in almost quantitative yields. Photolyses of
      less-substituted aryl alkanoates such as 2,6-dimethylphenyl (xylenyl), phenyl, 4
      methoxyphenyl (4-anisyl) and 4-methoxynaphthyl alkanoates 2-4 and 8 were also
      investigated to elucidate the reaction mechanism of acid-catalyzed
      phototransesterification. Irradiation of these esters afforded the corresponding
      photo-Fries rearrangement products 20-23 both in neutral and acidic acetonitrile
      with significant acceleration of the processes in the presence of acid. It was
      elucidated that the photolysis of the esters affords the geminate radical pair
      28, which in turn recombines to cyclohexadienone intermediates 29 and 30. Added
      acid accelerates not only the nucleophilic attack of alcohol to 29 and 30 but
      also other processes. Prolonged irradiation of the esters in neutral solution led
      to skeletal rearrangements of the initial product, affording isomeric
      alkylbenzenes. The phototransposition of cyclohexylmesitylene 15c via benzvalene
      intermediates was, on the contrary, retarded under acidic conditions. These acid
      controlled competitive photoreactions are representative examples, in which a
      catalytic amount of acid can alter the fate of reactive intermediates on both
      ground-state and excited-state surfaces.

PMID- 14690234
TI  - Steady-state and time-resolved studies on the formation of skatolyl radicals
      photosensitized by 2-benzoylthiophene.
AB  - Quenching of the excited triplet state of 2-benzoylthiophene (BT) by 3
      methylindole (CH3InH) leads to several neutral radicals resulting from formal
      hydrogen-atom abstraction. The transient absorption spectra of the BT ketyl
      radical (BTH) and the N-centered (CH3In) radical are directly detected by laser
      flash photolysis. From the differences between the spectra in the presence and
      the absence of oxygen, the C-centered skatolyl radical (CH2InH) is also observed.
      Accordingly, product studies demonstrate the formation of homodimers as well as
      cross-coupling products. They include BTH dimers (BTH-BTH, two stereoisomers),
      indolyl dimers (three different products) and products derived from reaction of
      skatolyl and BT ketyl radicals.

PMID- 14690235
TI  - Photochemically generated arylnitrenium ions: substituent effects on reactivity
      studied by laser flash photolysis.
AB  - Laser flash photolysis is used to examine reaction rates of four arylnitrenium
      ions: N-methyl-N-(4-chlorophenyl)-, -(4-biphenylyl)-, -(4-methylphenyl)-, and -(4
      methoxyphenyl)nitrenium ion. These intermediates are generated from photolysis of
      appropriately substituted N-aminopyridinium ions. Kinetic analysis of trapping
      rates shows that the nitrenium ions react with weak nucleophiles in the order 4
      Cl approximately 4-Me > 4-Ph > 4-OMe. Generally, amines react with the
      arylnitrenium ions at or near the diffusion-limited rate. Only in cases where the
      least reactive nitrenium ion (4-OMe) reacts with sterically hindered amines is
      any deviation from this generalization observed. The addition of a 2-acetyl
      substituent to these structures produces an interesting effect. In the case of
      the 4-Cl and 4-Ph analogs, the electron-withdrawing acetyl group decreases the
      rate of nucleophilic addition, yet with the 4-OMe and 4-Me compounds, the acetyl
      group increases the rate of addition. These results are discussed in terms of
      competing electronic and steric effects.

PMID- 14690236
TI  - Benzophenones in the higher triplet excited states.
AB  - Transient phenomena of benzophenone (BP) in the higher triplet excited state (Tn)
      have been investigated by the two-colour two-laser excitation method. Triplet
      energy transfer from BP(Tn) to quenchers (Q) occurred within the duration of a
      laser pulse (5 ns) to give Q(T1) with higher triplet energy than that of BP(T1).
      The quantum yield of the triplet energy-transfer quenching of BP(Tn) by CCl4 was
      found to be 0.0023 +/- 0.0002 from the bleaching of the transient absorption of
      BP(T1) and the absorbed photon number. It appears that internal conversion from
      BP(Tn) to BP(T1) is the predominant process. The lifetimes (tauTn) of BP(Tn) and
      several substituted benzophenones (BPs) in the higher triplet excited state
      [BPs(Tn)] were estimated from the dependence of the Q concentration on the
      efficiency of the triplet energy-transfer quenching of BP(Tn) by Q, and found to
      be 110-450 ps, depending on the nature of the substituents on the BPs. The effect
      of the substituents on tauTn may be explained by the energy gap between the Tn
      and T1 states, because the main deactivation pathway for BPs(Tn) is the internal
      conversion process. In contrast, the substituent effect on the lifetimes of
      BPs(T1) cannot be explained by the energy gap law. The transient behaviour of
      Q(T1) depends on the properties of the quencher. Sequential triplet energy
      transfer from Q(T1) to BP occurred for p-dichlorobenzene and tert-butylbenzene as
      quenchers, while Q(T1) reacted partly with Q to form triplet excimers (3Q2*) for
      benzene, chlorobenzene, and o-dichlorobenzene as quenchers. When CCl4 was used as
      the quencher, the homolytic cleavage of a C-Cl bond of CCl4(T1) occurred to give
      Cl* and Cl3C* radicals.

PMID- 14690237
TI  - The factor which determines whether excitation of charge-transfer complexes leads
      to final net products in comparison with the reactivity on excitation of one of
      the components.
AB  - Selective excitation of charge-transfer complexes of indene or acenaphthylene
      with various electron acceptors does or does not afford final net reaction
      products, depending on the free energy of the resulting radical ion pairs over
      the ground state, -deltaGBET, with threshold values. A similar factor governs the
      efficiency of the reaction on direct excitation of either the donor or the
      acceptor of their components, except that it does not fall to nil below the
      threshold and the reaction affords higher quantum yields than the selective
      excitation of the charge-transfer complex.

PMID- 14690238
TI  - Synthesis and photochemistry of isothiocoumarins fused to an additional pyranone
      or thiopyranone ring.
AB  - Both 4H,7H-benzo[1,2-c:4,3-c']dithiin-4,7-dione (3) and 4H,7H-thiino[4,3
      f][2]benzopyran- 4,7-dione (4) were synthesized from 1,2-bis(2
      hydroxyethyl)benzene (7). On irradiation (lambda > 390 nm) in acetonitrile the
      symmetric tricycle 3 affords selectively the two-fold cis-cisoid-cis dimer 10
      while the asymmetric tricycle 4 gives a 5:1 mixture of the cis-cisoid-cis dimers
      11 and 12. On irradiation in benzene in the presence of 2,3-dimethylbut-2-ene 3
      affords quantitatively a 3:2 mixture of the diastereomeric monocycloadducts 14c
      and 14t. Similarly, 4 gives a 3:2 mixture of 15c and 15t on irradiation in
      benzene in the presence of the same alkene, while in the presence of
      tetrachloroethene 17 is obtained selectively, all these monocycloadducts
      resulting from chemoselective addition of the alkene to the thiinone C-C double
      bond of 4, respectively.

PMID- 14690239
TI  - Origin of the N-methyl and N-phenyl substituent effects on the fluorescence
      vibronic structures of trans-4-aminostilbene and its derivatives in hexane.
AB  - The origin of the N-substituent effect on the room temperature fluorescence
      vibronic structures of trans-4-aminostilbene (1), its disubstituted derivatives
      (2 and 3), and the fused-ring analogs (4) in hexane has been investigated. The
      fluorescence spectra of aminostilbenes 1-4 in hexane are structured and the
      intensity ratio of the 0,1 vs. the 0,0 band decreases upon N-methyl or N-phenyl
      substitution, indicating that the N-substituents reduce the displacement in the
      equilibrium configuration (deltaQe) between the ground and the excited states.
      Our data are consistent with a planar fluorescing state for 1-4 in hexane. The N
      substituents affect the planarity of the ground state structures as well as the
      conjugation length allowed for exciton resonance, both of which are in accord
      with the observed progression in fluorescence vibronic structures. According to
      our analysis, the conformation effect that is associated with the geometry of the
      amino group appears to play a major role. The corresponding studies on the
      solvent effect suggest that the fluorescing state of 1-4 in more polar solvents
      is also a planar charge-transfer state.

PMID- 14690240
TI  - Excimer and intramolecular charge transfer chemiluminescence from
      electrogenerated ion radicals of donor-acceptor stilbenoids.
AB  - Electrongenerated chemiluminescence (ECL) of a series of intramolecular charge
      transfer (ICT) donor acceptor stilbenoid systems (2-9) bearing N,N-dimethylamino
      group as donor and pyridine, thiophene, quinoline or aryl groups as acceptors are
      studied. Most of the compounds (3-9) show ICT ECL through direct annihilation of
      the radical ions. For the weaker ICT compound (2), excimer ECL is observed
      instead.

PMID- 14690241
TI  - The unfolding intermediate state of calf intestinal alkaline phosphatase during
      denaturation in guanidine solutions.
AB  - The equilibrium unfolding of calf intestinal alkaline phosphatase in guanidinium
      chloride (GdmCl) solutions was studied by following the fluorescence and
      ultraviolet difference spectra. At low concentrations of GdmCl (< 1.6 M), the
      fluorescence intensity decreased with a slight red shift of the emission maximum
      from 332 nm to 344 nm. An unfolding intermediate state was observed at a broad
      concentration range of GdmCl as a denaturant (between 1.6 and 2.6 M). This
      intermediate was characterized by increased fluorescence emission intensity,
      ultraviolet difference absorption at 236 nm and 260 nm, as well as increased
      binding to the protein and red shift of the fluorescence probe 1
      anilinonaphthalene-8-sulfonic acid.

PMID- 14690242
TI  - Preparation and characterization of dimeric bovine hemoglobin tetramers.
AB  - Dimeric bovine hemoglobin (Hb) tetramers were prepared by a one-step solid phase
      adsorption method. Briefly, Hb was absorbed by the solid phase, Q Sepharose Fast
      Flow media, followed by reaction with the glutaraldehyde and elution procedure.
      Then, dimeric bovine Hb tetramers were formed and purified from Hb tetramers by
      anion-exchange chromatography based on Protein-Pak DEAE 8HR. The dimeric Hb
      tetramer showed a P50 value of 15.9 mm Hg, oxygen transporting efficiency of
      14.2%, and Hill coefficient of 1.72. The number of Bohr protons released for
      dimeric Hb tetramers was 0.59 H/tetramer, which was 39% of that of native bovine
      Hb. The number of chloride ions released on oxygenation was 0.60/tetramer for
      dimeric Hb tetramers, which was 46% of that of native bovine Hb.

PMID- 14690243
TI  - Study of refolding of calf intestinal alkaline phosphatase.
AB  - Calf intestinal alkaline phosphatase (CIP) was denatured in 3.0 M guanidine
      hydrochloride for 2 h at 25 degrees C, before being diluted 20-fold with 0.1 M,
      pH 8.0, Tris-HCl buffer solution containing various effector molecules such as
      Mg2+, Zn2+, and nucleotide phosphate. The reactivation courses of the enzyme were
      investigated by the level of activity recovery, the recovery rate constant, and
      the relative standard deviation of the data. In the presence of effectors, the
      courses under reducing and nonreducing conditions of disulfide bonds of protein
      were compared. It was concluded that for CIP, Mg2+ is a more efficient inducer of
      reconstitution of the active site and appears to play a specific role. In
      addition, the present study discusses the differences in the refolding effectors
      between bacterial and mammalian enzymes.

PMID- 14690244
TI  - Identification of gp17 glycoprotein and characterization of prostatic acid
      phosphatase (PAP) and carboxypeptidase E (CPE) fragments in a human seminal
      plasma fraction interacting with concanavalin A.
AB  - The decapacitating fraction of human seminal plasma, which strongly interacts
      with concanavalin A, is constituted by high mannose-type N-linked glycoproteins,
      most of them of less than 44 kDa. Each component with apparent molecular mass of
      30, 18, and 17 kDa respectively, as judged by SDS-PAGE, was submitted to "in gel"
      digestion with trypsin followed by HPLC separation of the peptides and
      sequencing. They were characterized at microscale as gp17, an aspartyl protease
      that possibly contributes to liquefaction of the seminal plasma coagulum, two
      fragments of human acid phosphatase (17 and 30 kDa, respectively), and a 17-kDa
      fragment of carboxypeptidase E. Neither the fragments of prostatic acid
      phosphatase nor that of carboxypeptidase E had been described before in the human
      seminal fluid. Very weak bands, of apparent molecular masses 44 and 52 kDa, are
      consistent with presence of small amounts of parent compounds, prostatic acid
      phosphatase and carboxypeptidase E.

PMID- 14690245
TI  - Effects of macromolecular crowding on the unfolding and the refolding of D
      glyceraldehyde-3-phosophospate dehydrogenase.
AB  - The effects of crowding agents, polyethylene glycol (PEG 20K), Dextran 70, and
      bovine serum albumin, on the denaturation of homotetrameric D-glyceraldehyde-3
      phosphate dehydrogenase (GAPDH, EC 1.2.1.12) in 0.5 M guanidine hydrochloride and
      the reactivation of the fully denatured enzyme have been examined quantitatively.
      Increasing the concentration of PEG 20K to 225 mg/ml decreases the rate constant
      of slow phase of GAPDH inactivation to 5% but with no change for the fast phase.
      Chaperone GroEL assists GAPDH refolding greatly and shows even higher efficiency
      under crowding condition. Crowding mainly affects refolding steps after the
      formation of the dimeric folding intermediate.

PMID- 14690246
TI  - A capillary electrophoresis technique for evaluating botulinum neurotoxin B light
      chain activity.
AB  - Botulinum neurotoxin B (BoNT/B) produces muscle paralysis by cleaving
      synaptobrevin/vesicle-associated membrane protein (VAMP), an 18-kDa membrane
      associated protein located on the surface of small synaptic vesicles. A capillary
      electrophoresis (CE) assay was developed to evaluate inhibitors of the
      proteolytic activity of BoNT/B with the objective of identifying suitable
      candidates for treatment of botulism. The assay was based on monitoring the
      cleavage of a peptide that corresponds to residues 44-94 of human VAMP-2 (V51)
      following reaction with the catalytic light chain (LC) of BoNT/B. Cleavage of V51
      generated peptide fragments of 18 and 33 amino acids by scission of the bond
      between Q76 and F77. The fragments and parent peptide were clearly resolved by
      CE, allowing accurate quantification of the BoNT/B LC-mediated reaction rates.
      The results indicate that CE is suitable for assessing the enzymatic activity of
      BoNT/B LC.

PMID- 14690247
TI  - Hypochlorite action on plasma fibronectin promotes its extended conformation in
      complexes with antibodies.
AB  - We investigated the influence of hypochlorite (HOCl/OCl-) on plasma fibronectin
      (Fn) aggregation and examined an affinity of Fn aggregates to Fn specific
      antibodies. Human plasma Fn HOCl/OCl(-)-mediated modification was monitored with
      differential OD method and with measurements of tryptophan fluorescence followed
      by acrylamide quenching of tryptophan emission. Antibody fibronectin complex
      formation was examined in ELISA systems with chemiluminescence (CL) detection.
      Results were expressed as an average of three experiments performed in
      triplicate. Fn aggregation/fragmentation was monitored with dynamic light
      scattering method. It was showed that HOCl/OCl- mediated chlorination promotes Fn
      aggregation/fragmentation with concomitant oxidation of tryptophan moieties and
      dichlorotyrosine formation. Quenching experiments revealed that in chlorinated Fn
      the percentage of intact tryptophan moieties buried in the hydrophobic Fn core
      increases as compared to unchlorinated Fn. In general, ELISA experiments showed
      that chlorination of plasma Fn diminished the number of available epitopes but
      for lower HOCl/OCl- concentrations (1-2 mM) the reverse effect is observed--the
      number of accessible fibronectin epitopes is increased when Fn adopts extended
      conformation in complex with antibody. Our results suggest that HOCl/OCl(-)
      mediated plasma Fn chlorination leads to the formation of soluble aggregates and
      is followed by refolding processes. Fn chlorination with low doses of HOCl/OCl-
      promotes extended Fn conformation which in turn increases affinity toward
      specific antibodies and may promote Fn-IgG cluster formation. Thus it seems
      possible that mildly chlorinated plasma Fn promotes formation of IgG clusters
      which in turn may activate neutrophils.

PMID- 14690248
TI  - Inhibition of nicotinoprotein (NAD+-containing) alcohol dehydrogenase by trans-4
      (N,N-dimethylamino)-cinnamaldehyde binding to the active site.
AB  - Ethanol oxidation by nicotinoprotein alcohol dehydrogenase (np-ADH) from the
      bacterium Amycolatopsis methanolica is inhibited by trans-4-(N,N-dimethylamino)
      cinnamaldehyde through direct binding to the catalytic zinc ion in a substrate
      like geometry. This binding is accompanied by a characteristic red shift of the
      aldehyde absorbance from 398 nm to 467 nm. Np-ADH is structurally related to
      mammalian ADH class I, and a model of np-ADH shows how the cinnamaldehyde
      derivative can be accommodated in the active site of the nicotinoprotein,
      correlating the structural and enzymological data.

PMID- 14690249
TI  - Kinetic inactivation study of mushroom tyrosinase: intermediate detection by
      denaturants.
AB  - The unfolding and inhibition study of mushroom tyrosinase have been studied in
      the presence of different denaturants such as sodium dodecyl sulfate (SDS),
      guanidine hydrochloride (GdnHCl), and urea. The kinetic two-phase rate constants
      were commonly measured from semilogarithmic plots of the activity versus time,
      which resolved into two straight lines, indicating that the inactivation process
      consisted of fast and slow phases as a first-order reaction. This result also
      implied that transient partially folded intermediate existed during tyrosinase
      unfolding pathway. Mushroom tyrosinase had different behaviors to denaturants in
      regard with: noncooperative binding manner by SDS while cooperative interactions
      by GdnHCl and urea; in equilibrium state, SDS-micelle never completely
      inactivated enzyme activity while GdnHCl has single step denaturation and urea
      induced a typical transition-like process. Various kinetic parameters for each
      denaturant were calculated and the possible unfolding pathway scheme was
      discussed.

PMID- 14690250
TI  - A new continuous spectrophotometric assay method for DOPA oxidase activity of
      tyrosinase.
AB  - Sensitive assay methods for tyrosinase are essential not only for the
      understanding the process of pigment production but also for the development of
      effective inhibitors of tyrosinase. To develop an efficient assay method, we
      applied thymol blue to reaction mixtures. The enzyme kinetic study revealed that
      DOPA oxidase activity of tyrosinase in thymol blue-applied reaction system was
      more sensitively measured, even under lower enzyme units compared with the
      previous report with significant enhancement of Vmax while affinity change on
      substrate was not observed. To test whether this method could be applicable to
      the inhibition and the inactivation kinetic study of tyrosinase, the effect of
      kojic acid, a well-known tyrosinase inhibitor, and sodium chloride respectively,
      have been studied. Conclusively, thymol blue method can assay tyrosinase activity
      with sensitivity and is applicable to the inhibition and the inactivation study
      of tyrosinase.

PMID- 14690251
TI  - Inactivation kinetics of mushroom tyrosinase by cetylpyridinium chloride.
AB  - Cetylpyridinium chloride (CPC) was found to inactivate tyrosinase from mushroom
      (Agaricus bisporus). CPC can bind to the enzyme molecule and induce the enzyme
      conformation changes. The fluorescence intensity (at 338.4 nm) of the enzyme
      decreased distinctly with increasing CPC concentrations, and a new little
      fluorescence emission peak appeared near 372 nm. The inactivation of the enzyme
      by CPC had first been studied by using the kinetic method of the substrate
      reaction described by Tsou. The results showed that the enzyme was inactivated by
      a complex mechanism that had not been previously identified. The enzyme first
      quickly binds with CPC reversibly and then undergoes a slow irreversible
      inactivation. The inactivation reaction is a single molecule reaction and the
      apparent inactivation rate constant is a saturated trend being independent of CPC
      concentration if the concentration is sufficiently high. The micro rate constants
      of inactivation and the association constant were determined.

PMID- 14690252
TI  - Amino acid sequence of the alpha- and beta-globin chains of the Erabu sea snake
      (Laticaudia semifasciata).
AB  - We determined the complete amino acid sequences of the Erabu sea snake
      (Laticaudia semifasciata) hemoglobin by analyzing the intact globin chains,
      enzymatically digested fragments, and chemical cleavage fragments to clarify the
      molecular evolution and phylogenetic classification of the sea snake. The Erabu
      sea snake has two types of hemoglobin components, Hb-I and Hb-II, which contain
      different alpha- and beta-chains. This is the second report of the complete
      primary structure for hemoglobin of snakes. The sequences were compared with
      those of other reptilian hemoglobins. Amino acids at positions critical for the
      structure and physiological functions of hemoglobin were loosely conserved. The
      requirements for binding of ATP and of diphosphoglycerate as allosteric effectors
      of beta-globins seemed to be fulfilled.

PMID- 14690253
TI  - Homocysteine-lowering therapy in renal disease.
AB  - Hyperhomocysteinemia is a potential risk factor for vascular disease and is
      associated with endothelial dysfunction, a predictor of adverse cardiovascular
      events. Renal patients (end-stage renal failure (ESRF) and transplant recipients
      (RTR)) exhibit both hyperhomocysteinemia and endothelial dysfunction with
      increasing evidence of a causative link between the 2 conditions. The elevated
      homocysteine appears to be due to altered metabolism in the kidney (intra-renal)
      and in the uremic circulation (extra-renal). This review will discuss 18
      supplementation studies conducted in ESRF and 6 in RTR investigating the effects
      of nutritional therapy to lower homocysteine. The clinical significance of
      lowering homocysteine in renal patients will be discussed with data on the
      effects of B vitamin supplementation on cardiovascular outcomes such as
      endothelial function presented. Folic acid is the most effective nutritional
      therapy to lower homocysteine. In ESRF patients, supplementation with folic acid
      over a wide dose range (2 - 20 mg/day) either individually or in combination with
      other B vitamins will decrease but not normalize homocysteine. In contrast, in
      RTR similar doses of folic acid normalizes homocysteine. Folic acid improves
      endothelial function in ESRF patients, however this has yet to be investigated in
      RTR. Homocysteine-lowering therapy is more effective in ESRF patients than RTR.

PMID- 14690254
TI  - ACE inhibitorenalapril diminishes albuminuria in patients with cystinosis.
AB  - BACKGROUND/AIMS: Cystinosis, a rare autosomal recessive disease, manifests with
      renal Fanconi syndrome during the first year of life. Interstitial damage is a
      major cause of renal failure in patients with cystinosis. We presume that
      albuminuria contributes to the development of renal failure in these patients.
      The aim of this study was to examine whether the administration of ACE inhibitor
      enalapril diminishes albuminuria in patients with cystinosis. METHODS: Five
      patients with cystinosis aged 4 - 9 years were studied. All patients had Fanconi
      syndrome and were treated with cysteamine. Median creatinine clearance was 48
      ml/min/1.73 m2 (range 21 - 61). The excretion of albumin and alpha1 microglobulin
      as well as arterial blood pressure and serum creatinine were evaluated before and
      at 3 months on oral administration of enalapril (0.15 mg/kg once daily). RESULTS:
      At 3 months on enalapril, albuminuria decreased in all patients (1,042 vs 629 mg
      per 24 h, p < 0.05). The median reduction of albuminuria was 43% (range: 4 - 72%,
      p < 0.05). Urinary excretion of alpha1 microglobulin remained constant. Systolic
      blood pressure decreased from median 110 - 100 mmHg (p < 0.05), while diastolic
      blood pressure remained stable (median 60 mmHg). Creatinine clearance decreased
      from median 48 - 45 ml/min/1.73 m2 (p < 0.05) and returned to previous values
      after discontinuation of enalapril. CONCLUSION: ACE inhibitor enalapril
      diminishes albuminuria in patients with cystinosis and might be used in these
      patients in order to slow the progression of renal insufficiency attributed to
      proteinuria.

PMID- 14690255
TI  - Mizoribine oral pulse therapy for patients with disease flare of lupus nephritis.
AB  - AIM: Mizoribine (MZR) is a newly developed immunosuppressive agent in Japan. To
      relieve disease flare of lupus nephritis, a prospective pilot study of oral MZR
      pulse therapy (a phase II trial) is conducted as an alternative therapy to dose
      up of corticosteroids. METHODS: Six Japanese patients with biopsy-proven lupus
      nephritis who experienced disease flare were prospectively evaluated. MZR at a
      dose of 5 - 10 mg/kg per day (up to 500 mg) in 1 or 2 divided daily doses was
      orally administered twice a week for 3 months. At the time of disease flare, 4
      patients had refused to take dose up of corticosteroids, and the other 2 had
      complained of opportunistic infection. RESULTS: At presentation, urine protein
      excretion, serum hemolytic complement activity (CH50) and serum anti-dsDNA
      antibody were 1.9 +/- 0.6 g/day, 15.7 +/- 5.8 U/ml (normal 23 - 46 U/ml) and
      164.8 +/- 184.0 IU/ml (normal < 12.0 IU/ml), respectively. Urine protein
      excretion and serum anti-dsDNA antibody decreased significantly following MZR
      oral pulse therapy (0.2 +/- 0.1 g/day and 29.7 +/- 23.4 IU/ml (p < 0.05),
      respectively), and serum CH50 recovered to normal (35.1 +/- 10.4 U/ml, p < 0.05).
      Moreover, a significant histologic improvement was observed in a patient who
      received repeat renal biopsies at pre- and post-treatment. Reported peak serum
      MZR levels enough to inhibit human mixed-lymphocyte reaction (3.0 - 6.0
      microg/ml) were achieved in all patients. No serious adverse effects were
      observed. CONCLUSION: Although we had no control subjects in this series, MZR
      oral pulse therapy may be of benefit to a proportion of patients with disease
      flare of lupus nephritis as an alternative therapy to dose up of corticosteroids.

PMID- 14690256
TI  - Diagnostic role of [F-18]-FDG positron emission tomography in restaging renal
      cell carcinoma.
AB  - AIMS: To retrospectively assess the diagnostic utility of positron emission
      tomography (PET) with 18F-fluorodeoxyglucose (FDG) in restaging renal cell
      carcinoma. MATERIALS AND METHODS: We performed whole-body PET scans (45 minutes
      after intravenous injection of 10 - 15 mCi FDG) for restaging 25 patients (18
      male, 7 female, 42 - 81 years old) with known or suspected metastatic renal cell
      carcinoma. Prior treatments included immunotherapy (n = 1), nephrectomy (n = 16),
      nephrectomy followed by chemotherapy (n = 3), by radiation therapy (n = 1), and
      by combined chemoradiation therapy (n = 4). Contrast-enhanced chest, abdomen and
      pelvis CT studies were available for all patients. Diagnostic validation was by
      histological sampling (n = 2) and clinical and imaging follow-up for up to 1 year
      (n = 23). RESULTS: PET was concordant with the findings of CT in 18 patients (3
      TN, 15 TP). PET was discordant with CT in 7 patients (28% of total). PET was
      falsely negative in 6 of these patients and did not demonstrate hypermetabolism
      in pulmonary (n = 4), mediastinal (n = 2), adrenal (n = 1) and lytic osseous (n =
      2) metastatic lesions. PET was falsely positive in the remaining 1 patient in the
      discordant group with lumbar facet arthropathy. The diagnostic performance of PET
      in detection of recurrent and metastatic renal cell carcinoma revealed a
      sensitivity of 71%, specificity of 75%, accuracy of 72%, negative predictive
      value of 33% and positive predictive value of 94%. CONCLUSIONS: FDG PET
      demonstrates modest accuracy in the diagnostic imaging evaluation of patients
      with suspected or known metastatic renal cell carcinoma. A negative study may not
      exclude disease while a positive study is suspicious for malignancy.

PMID- 14690257
TI  - Does hepatitis C virus infection increase hematocrit and hemoglobin levels in
      hemodialyzed patients?
AB  - OBJECTIVE: Some case reports indicated that red cell status increased after
      hepatitis C viral infection. The aim of study was to define the influence of
      hepatitis C infection (HCV) on red cell status in hemodialyzed patients.
      MATERIALS AND METHODS: A total of 49 (21 anti-HCV-positive and 28 anti-HCV
      negative) patients with ESRD were included in this study. Exclusion criteria were
      blood transfusion and massive blood loss in the last 6 months preceding the
      study. None of the patients used any drug containing aluminum. RESULTS: The
      prevalence of anti-HCV antibody was 42.8%. Mean age was 51.6 +/- 14.3 in anti-HCV
      (+) group and 50.4 +/- 17.0 in anti-HCV (-) group. There was no statistically
      significant difference between the ages of the 2 groups. Mean duration time of
      hemodialysis was significantly longer in patients with anti-HCV antibody (+)
      group (54.9 +/- 34.2 months) compared to anti-HCV-negative group (12.5 +/- 9.0
      months) (p < 0.001). Mean hemoglobin (Hb) and hematocrit (Htc) levels were
      significantly higher in anti-HCV-positive patients than in anti-HCV-negative
      patients (Hb: 10.4 +/- 1.8 g/dl, Htc: 30.5 +/- 5.5% vs Hb: 8.8 +/- 1.7 g/dl, Htc:
      26.1 +/- 5.3%) (for Hb p < 0.005, for Htc p < 0.007). There was no significant
      difference regarding the usage ofrHuEPO between the 2 study groups (57.1% in anti
      HCV antibody (+)/59.3% in anti-HCV antibody (-)) (p > 0.05). All patients not
      receiving rHuEPO did so because of economical reasons. Serum AST and ALT levels
      were significantly higher in the anti-HCV antibody-positive group compared with
      the anti-HCV antibody-negative group. (AST p < 0.04, ALT p < 0.04). CONCLUSION:
      Anti-HCV antibody-positive ESRD patients have higher hemoglobin and hematocrit
      levels compared to HCV-negative patients.

PMID- 14690258
TI  - Delayed renal allograft dysfunction and cystitis associated with human
      polyomavirus (BK) infection in a renal transplant recipient: a case report and
      review of literature.
AB  - Human polyomavirus type BK (BKV) associated nephritis (BKVAN) has recently
      emerged as an important cause of renal allograft dysfunction and failure. Early
      recognition of this entity as a cause of allograft dysfunction is extremely
      important since misdiagnosis can accelerate graft loss. We report a case of BKVAN
      that presented with symptoms related to cystitis, and review the risk factors,
      the diagnostic tools and the approach to treatment of BK virus associated
      allograft nephropathy.

PMID- 14690259
TI  - Disseminated ochroconis gallopavum infection in a renal transplant recipient: the
      first reported case and a review of the literature.
AB  - Ochroconis gallopavum is a potentially fatal dematiaceous fungus causing
      opportunistic infections in immunocompromised hosts. We report the first case of
      disseminated O. gallopavum infection in a 13-year-old renal transplant recipient,
      which involved the brain, lung and spleen. He was treated with amphotericin B,
      itraconazole and voriconazole, a new antifungal agent first used to treat such an
      infection. Besides antifungal treatment, all immunosuppressive agents were
      stopped and automated peritoneal dialysis was resumed. The initial infection was
      under control with both clinical and radiological improvements after treatment.
      However, the patient later acquired Acremonium spp. peritonitis; he failed to
      respond to high-dose amphotericin B, and finally succumbed. A total of 13
      reported O. gallopavum human infections, including the one described here, are
      reviewed. The most common site of involvement is the brain and the crude
      mortality rate is up to 46%. As the disease is potentially lethal in
      immunocompromised hosts, empirical antifungal coverage should be considered in
      post-renal transplant recipients with suspected brain abscess. Early biopsy of
      lesion for histopathological and microbiological diagnosis would be essential in
      managing such cases.

PMID- 14690261
TI  - Acute renal failure in a hypothyroid patient with rhabdomyolysis.
AB  - A 49-year-old hypothyroid man developed rhabdomyolysis and acute renal failure.
      He had been on thyroid replacement therapy for 17 years following removal of a
      benign pituitary tumor. Rhabdomyolysis was diagnosed by elevated liver enzymes,
      CPK, and creatinine. The case illustrates how hypothyroidism can cause
      rhabdomyolysis and subsequently, acute renal failure.

PMID- 14690260
TI  - Improved pregnancy outcome in a patient with renal allograft nephropathy
      undergoing temporary hemodialysis.
AB  - We report a case of a woman with a poorly functioning renal allograft and a
      positive anti-cardiolipin antibody who was dialysis-independent and conceived 18
      months following her transplant. She was electively maintained on hemodialysis
      during the pregnancy and delivered a live infant at 31 weeks gestation. Her renal
      function returned to prepregnancy levels post partum and she remained dialysis
      independent.

PMID- 14690262
TI  - Idiopathic spontaneous bladder rupture in an intoxicated patient.
AB  - Spontaneous bladder rupture is a rare condition associated with significant
      morbidity and mortality. We describe a case that occured following a period of
      alcohol intoxication and presented as acute renal failure. The factors that
      contribute to this condition in an intoxicated person are outlined and useful
      clinical markers are suggested. This case demonstrates the difficulties with
      diagnosis and the need for a high index of suspicion.

PMID- 14690263
TI  - A rare case of central post-gravid diabetes insipidus.
AB  - Central diabetes insipidus (CDI) arising in the puerperal period has been
      attributed mainly to Sheehan's syndrome or to lymphocytic infundibulo
      neurohypophysitis. We report the case of a 24-year-old woman who came to our
      observation for the appearance, 3 weeks after a normal delivery, of a polyuric
      polydipsic syndrome. Measurements of urinary volumes, plasma osmolality and
      urinary osmolality, in conditions of free water intake, water deprivation and a
      water deprivation-vasopressin administration test, demonstrated CDI. Brain
      magnetic resonance imaging showed a normal morphology of the adenohypophysis and
      total absence of the neurohypophysis. Assays of the pituitary hormones were found
      to be within normal limits. These results, incompatible with a diagnosis of
      Sheehan's syndrome and lymphocytic infundibulo-neurohypophysis, excluded all the
      other known causes of acquired CDI. Our diagnosis was therefore of post-gravid
      idiopathic CDI. Thus, it is possible that in the puerperal period other diseases
      of the posterior hypophysis may develop, of unknown etiopathogenesis but equally
      responsible for CDI.

PMID- 14690264
TI  - Nephrotic syndrome associated with carcinoma of the breast.

PMID- 14690266
TI  - Acute IgA nephropathy following keloid scar formation due to burn injury.

PMID- 14690265
TI  - Minimal change nephropathy and renal tuberculosis.

PMID- 14690267
TI  - Left atrial myxoma associated with systemic AA amyloidosis.

PMID- 14690268
TI  - CRP and depression in patients on chronic dialysis.

PMID- 14690269
TI  - Proceedings of the International Workshop on Weak Electric Field Effects in the
      Body. United Kingdom, March 24-25, 2003.

PMID- 14690270
TI  - WHO's health risk assessment of ELF fields.
AB  - The World Health Organization (WHO), the International Commission on Non-Ionizing
      Radiation Protection (ICNIRP), WHO's scientific collaborating centres (including
      the UK's National Radiological Protection Board (NRPB)) and over 50 participating
      Member States are participants of WHO's International EMF Project. As part of
      WHO's health risk assessment process for extremely low frequency fields (ELF),
      this workshop was convened by NRPB to assist WHO in evaluating the potential
      health impacts of electrical currents and fields induced by ELF in molecules,
      cells, tissues and organs of the body. This paper describes the process by which
      WHO will conduct its health risk assessment. WHO is also trying to provide
      information on why exposure to ELF magnetic fields seems to be associated with an
      increased incidence of childhood leukaemia. Are there mechanisms that could lead
      to this health outcome or does the epidemiological evidence incorporate biases or
      other factors that need to be further explored?

PMID- 14690271
TI  - Mechanisms of interaction of extremely low frequency electric fields and
      biological systems.
AB  - This article reviews mechanisms of interaction between extremely-low frequency
      (ELF) fields and biological systems. The emphasis is on simple quantitative
      models, supplemented by results of more detailed computer analysis. Scaling
      relations are reviewed which underlie the coupling of external fields to the
      inside of the body, and of extracellular fields to potentials induced in cell
      membranes. The relation between time domain and frequency thresholds for
      stimulating excitable tissues is reviewed, based on the work of Reilly. A range
      of thermal and non-thermal interaction mechanisms are reviewed, with respect to
      the question of possible effects of weak ELF fields in biological systems. Each
      mechanism is characterised by a threshold field strength (below which no
      observable response is produced) and dynamics; in each case, the anticipated in
      situ tissue strengths for producing observable effects are far higher than the
      range of 'weak' fields considered in this review. However, the bioeffects
      literature is unclear in many places, with numerous speculations about possible
      mechanisms for weak field effects and many reports of effects that are not
      clearly interpretable in terms of the mechanisms discussed in this article.

PMID- 14690272
TI  - Neuronal ion channels and their sensitivity to extremely low frequency weak
      electric field effects.
AB  - Neuronal ion channels are gated pores whose opening and closing is usually
      regulated by factors such as voltage or ligands. They are often selectively
      permeable to ions such as sodium, potassium or calcium. Rapid signalling in
      neurons requires fast voltage sensitive mechanisms for closing and opening the
      pore. Anything that interferes with the membrane voltage can alter channel gating
      and comparatively small changes in the gating properties of a channel can have
      profound effects. Extremely low frequency electrical or magnetic fields are
      thought to produce, at most, microvolt changes in neuronal membrane potential. At
      first sight, such changes in membrane potential seem orders of magnitude too
      small to significantly influence neuronal signalling. However, in the central
      nervous system, a number of mechanisms exist which amplify signals. This may
      allow such small changes in membrane potential to induce significant
      physiological effects.

PMID- 14690273
TI  - Rapporteur report: interaction mechanisms.
AB  - Three papers were presented in the session on the interaction mechanisms of weak
      electric fields induced in the body by exposure to extremely low frequency
      electromagnetic fields with biological systems, particularly the central nervous
      system. The first paper considered the plausibility of various interaction
      mechanisms. The second paper dealt with voltage gated ion channels and the way in
      which they could be involved in the generation of biological effects. The final
      paper described a kinetic proofreading mechanism, sensitive, in theory, to very
      low level perturbations. These papers were discussed in a plenary session and in
      one breakout group, all of which are briefly summarised in this report.

PMID- 14690274
TI  - Effects of weak electric fields on the activity of neurons and neuronal networks.
AB  - Electric fields applied to brain tissue will affect cellular properties. They
      will hyperpolarise the ends of cells closest to the positive part of the field,
      and depolarise ends closest to the negative. In the case of neurons this affects
      excitability. How these changes in transmembrane potential are distributed
      depends on the length constant of the neuron, and on its geometry; if the neuron
      is electrically compact, the change in transmembrane potential becomes an almost
      linear function of distance in the direction of the field. Neurons from the
      mammalian hippocampus, maintained in tissue slices in vitro, are significantly
      affected by fields of around 1-5 V m(-1).

PMID- 14690275
TI  - Electric field effects in hyperexcitable neural tissue: a review.
AB  - Uniform electric fields applied to neural tissue can modulate neuronal
      excitability with a threshold value of about 1 mV mm(-1) in normal physiological
      conditions. However, electric fields could have a lower threshold in conditions
      where field sensitivity is enhanced, such as those simulating epilepsy. Uniform
      electrical fields were applied to hippocampal brain slices exposed to picrotoxin,
      high potassium or low calcium solutions. The results in the low calcium medium
      show that neuronal activity can be completely blocked in 10% of the 30 slices
      tested with a field amplitude of 1 mV mm(-1). These results suggest that the
      threshold for this effect is clearly smaller than 1 mV mm(-1). The hypothesis
      that the extracellular resistance could affect the sensitivity to the electrical
      fields was tested by measuring the effect of the osmolarity of the extracellular
      solution on the efficacy of the field. A 10% decrease in osmolarity resulted in a
      56% decrease (n = 4) in the minimum field required for full suppression. A 14% in
      osmolarity produced an 81% increase in the minimum field required for full
      suppression. These results show that the extracellular volume can modulate the
      efficacy of the field and could lower the threshold field amplitudes to values
      lower than approximately 1 mmV mm(-1).

PMID- 14690276
TI  - 50-60 Hz electric and magnetic field effects on cognitive function in humans: a
      review.
AB  - This paper reviews the effect of 50-60 Hz weak electric, magnetic and combined
      electric and magnetic field exposure on cognitive functions such as memory,
      attention, information processing and time perception, as determined by
      electroencephalographic methods and performance measures. Overall, laboratory
      studies that have investigated the acute effects of power frequency fields on
      cognitive functioning in humans are heterogeneous, in terms of both electric and
      magnetic field (EMF) exposure and the experimental design and measures used.
      Results are inconsistent and difficult to interpret with regard to functional
      relevance for possible health risks. Statistically significant differences
      between field and control exposure, when they are found, are small, subtle,
      transitory, without any clear dose-response relationship and difficult to
      reproduce. The human performance or event related potentials (ERPs) measures that
      might specifically be affected by EMF exposure, as well as a possible cerebral
      structure or function that could be more sensitive to EMF, cannot be better
      determined.

PMID- 14690277
TI  - Interaction of low frequency electric fields with the nervous system: the retina
      as a model system.
AB  - The retina provides an example of effects, the visually perceived 'phosphenes',
      being generated in nervous tissue by external electric or magnetic fields of low
      frequency and intensity. What is known about the cellular mechanisms by which the
      phosphenes are generated is reviewed, whether they provide useful information for
      setting limits on the magnitude of induced electric fields to which nervous
      tissue can be safely exposed is assessed, and some difficulties in translating
      these values of internal fields into safe values of external electric or magnetic
      fields are considered.

PMID- 14690278
TI  - Dosimetry considerations in the head and retina for extremely low frequency
      electric fields.
AB  - Magnetophosphenes are investigated from the viewpoint of electromagnetic
      dosimetry. Induced current density and internal electric fields at the threshold
      of perception are estimated by analytical and numerical calculations, assuming
      different models. Dosimetry for electrophosphenes is also discussed and compared
      with that for magnetophosphenes. The distribution of current density and internal
      electric fields is consistent with the experimental observation that flashing
      sensations reach their greatest intensity at the periphery of the visual field,
      for both electro and magnetophosphenes. The estimated thresholds in internal
      electric fields are consistent for magnetophosphenes and for electrophosphenes,
      respectively. The magnitudes of the thresholds, however, differ by about 10-fold.
      The thresholds in induced current density are critically dependent on the
      conductivity of the eye assumed for the calculations. The effect of thin membrane
      structure is also discussed with regard to the difference between electric field
      and magnetic field exposures.

PMID- 14690279
TI  - Rapporteur report: weak field interactions in the central nervous system.
AB  - Experimental evidence was presented of the interaction of extremely low frequency
      (ELF) physiologically weak electric fields (that is, internal fields of around 1
      1000 mV m(-1)) with tissues of the central nervous system and the consequences of
      this for visual and cognitive function. These internal fields are higher than
      those induced in the body by exposure to environmental EMFs, but are small
      compared to nerve excitation thresholds. Two papers considered the effect of weak
      electric fields directly applied to hippocampal tissue in vitro on neuronal
      excitability assessed from evoked responses and on the modulation of neural
      network activity involving large numbers of individual neurons. A review was
      presented of the effects on electrical measures of perceptual and cognitive
      processes and on the performance of various behavioural tasks in volunteers
      exposed to electromagnetic fields. Finally, two papers addressed the visual
      perception of flickering light--phosphenes--in volunteers exposed to ELF magnetic
      fields. The first examined possible physiological origins of this phenomenon and
      the second assessed the induced electric fields and currents in the retina, using
      complex dosimetric modelling. These papers were discussed in several plenary
      sessions and in one breakout group, all of which are briefly summarised in this
      report.

PMID- 14690280
TI  - Cardiac electrophysiology: theoretical considerations of a potential target for
      weak electromagnetic field effects.
AB  - With the widespread introduction of extra high voltage power transmission lines
      in the 1960s, and subsequent to early reports from Soviet Union scientists about
      health risks for transformer station personnel, public concern regarding the
      effects of electromagnetic fields (EMFs) on biological function has given rise to
      a large number of investigations and legislation to limit domestic and
      occupational exposure to EMFs. The underlying rationale for concern is related to
      the fact that living cells are electrically active, which makes them potentially
      vulnerable to electromagnetic interference. In the heart, electrical activity is
      crucial in coordinating the contraction of millions of cardiac cells, and
      disturbances in cardiac electrical activity, also known as arrhythmias, are often
      life threatening. Electrical fields induced in the heart by weak external EMFs
      (such as those encountered in a domestic setting) are understood to be at least 2
      orders of magnitude smaller (< 1%) than those that occur naturally as an
      intrinsic consequence of cardiac activity. Using quantitative models of cardiac
      cellular electrophysiology, the effect of weak (1%) manipulation of key current
      mechanisms that give rise to the electrical activity of the heart is therefore
      assessed.

PMID- 14690281
TI  - Circadian neuroendocrine physiology and electromagnetic field studies:
      precautions and complexities.
AB  - The suppression of melatonin by exposure to low frequency electromagnetic fields
      (EMFs) 'the melatonin hypothesis'. has been invoked as a possible mechanism
      through which exposure to these fields may result in an increased incidence of
      cancer. While the effect of light on melatonin is well established, data showing
      a similar effect due to EMF exposure are sparse and, where present, are often
      poorly controlled. The current review focuses on the complexities associated with
      using melatonin as a marker and the dynamic nature of normal melatonin regulation
      by the circadian neuroendocrine axis. These are issues which the authors believe
      contribute significantly to the lack of consistency of results in the current
      literature. Recommendations on protocol design are also made which, if followed,
      should enable researchers to eliminate or control for many of the confounding
      factors associated with melatonin being an output from the circadian clock.

PMID- 14690282
TI  - Endogenous electric fields in embryos during development, regeneration and wound
      healing.
AB  - All embryos that have been investigated drive ionic currents through themselves
      and these currents will generate internal electric fields. Here, those examples
      in which such fields have been measured directly are discussed. The first such
      measurements were made in chick embryos and about 20 mV mm(-1) was measured near
      the posterior intestinal portal in 2-4 day-old embryos. This electric field is
      important for the development of tail structures because reducing its magnitude
      results in abnormal tail development. The second embryonic electric field
      measured directly was in the axolotl, where a rostral-caudal field of about the
      same magnitude was detected. Modification of this field during neurulation but
      not gastrulation caused developmental abnormalities. Most recently, the
      development of left-right asymmetry in frog and chick embryos was found to
      require a voltage difference between blastomeres at a very early developmental
      stage. This field was measured in the chick embryo to be 10-20 mV mm(-1) across
      the primitive streak. Mammalian skin wounds generate 150 mV mm(-1) fields lateral
      to the wound and corneal epidermal wounds exhibit lateral fields of 40 mV mm(-1).
      The presence of these endogenous fields would suggest that exposures to external
      electric fields should be limited to magnitudes of less than 0.1 V m(-1).

PMID- 14690283
TI  - Developmental effects of extremely low frequency electric and magnetic fields.
AB  - Developmental effects of extremely low frequency (ELF) electric and magnetic
      fields are briefly reviewed in this paper. The results of animal studies on ELF
      electric fields are rather consistent, and do not suggest adverse effects on
      development. The results of studies on ELF magnetic fields suggest effects on
      bird embryo development, but not consistently in all studies. Results from
      experiments with other non-mammalian species have also suggested effects on
      developmental stability. In mammals, pre-natal exposure to ELF magnetic fields
      does not result in strong adverse effects on development. The only finding that
      shows some consistency is increase of minor skeleton alterations. Epidemiological
      studies do not establish an association between human adverse pregnancy outcomes
      and maternal exposure to ELF lields, although a few studies have reported
      increased risks associated with some characteristics of magnetic field exposure.
      Taken as a whole, the results do not show strong adverse effects on development.
      However, additional studies on the suggested subtle effects on developmental
      stability might increase our understanding of the sensitivity of organisms to
      weak ELF fields.

PMID- 14690284
TI  - Rapporteur report: other tissues.
AB  - This report covers the session devoted to 'other tissues'. It considers the
      effects of internal electric fields such as those induced by exposure to weak,
      extremely low frequency (ELF) electromagnetic fields, on cardiac physiology,
      neuroendocrine (pineal) function and on the processes of tissue repair and
      embryonic development. Summaries are provided for each of the papers presented,
      and the major aspects of the plenary session are discussed. Overall, these
      tissues and processes were not considered to be sensitive to the direct effects
      of weak ELF fields, although indirect effects may occur via field induced changes
      to the central nervous system.

PMID- 14690285
TI  - Less access to care for children with Medicaid.

PMID- 14690286
TI  - Radiologic case study. Hibernoma.

PMID- 14690287
TI  - A technique to prevent Ender nail back-out.
AB  - Ender nails are advantageous in the treatment of certain fractures; however,
      inadequate fixation and back-out are frequent complications. This article
      presents a simple looping technique that prevents Ender nail back-out.

PMID- 14690288
TI  - Economic consequences of operative delay for hip fractures in a non-profit
      institution.
AB  - This retrospective study evaluated the economic consequences of delaying hip
      fracture surgery in 191 elderly patients. Data was collected regarding fracture
      type, surgery, timing of surgery, background diseases, postoperative hospital
      stay, and complications. In addition, calculation of the drugs administered to
      the patients, cost of the surgery, blood transfusion, physiotherapy, laboratory
      examinations, radiographs, and any financial data were evaluated. Spending more
      resources for performing hip surgery within 48 hours is more cost-effective than
      delaying surgery past the third day.

PMID- 14690289
TI  - Immunohistological detection of relaxin binding to anterior cruciate ligaments.
AB  - Relaxin, a member of the insulin-like growth factor family, alters collagen
      metabolism in fibroblasts. It was hypothesized that relaxin interacts with the
      anterior cruciate ligament (ACL), contributing to its elasticity. Twelve ACL
      specimens were collected from reconstruction surgeries, sectioned, rinsed, and
      exposed to rh-relaxin overnight. Polyclonal antirelaxin antibodies, in
      conjunction with HRP-AEC, localized areas of tissue binding. Controls were used
      to infer binding specificity. Staining was present in the positive control and
      all 12 ACL specimens; little or no staining occurred in the negative controls.
      These data suggest that relaxin binding to the ACL is specific, indicative of a
      receptor-mediated event.

PMID- 14690290
TI  - Allograft reconstruction for extensor mechanism rupture after total knee
      arthroplasty: 4.8-year follow-up.
AB  - Three patients who experienced extensor mechanism rupture after total knee
      arthroplasty underwent reconstruction using an allograft consisting of quadriceps
      tendon, patella, patellar tendon, and tibial tubercle. All patients who failed
      initial attempts to repair the extensor mechanism disruption achieved pain relief
      at average 4.8-year follow-up. Patients were able to extend their knee actively
      against resistance. Ambulation with full weight bearing was possible in all
      patients; however, one patient required a cane. Few reports have been published
      on allograft reconstruction of the extensor mechanism. The current study supports
      its use for patients who have failed to achieve knee extension with
      reconstruction by other means.

PMID- 14690291
TI  - Giant-cell tumors of bone and progesterone receptors.
AB  - Estrogen receptors, progesterone receptors, and cathepsin D were determined in 10
      patients with giant-cell bone tumor. Progesterone receptors were expressed in 5
      of 10 patients tested, whereas low levels of estrogen receptors were found in 1
      patient. Cathepsin D levels were elevated in 5 of 5 samples studied. High values
      of progesterone receptors correlated with low tumor grade. Cathepsin D levels
      correlated negatively with tumor grade but positively with local tumor expansion.
      Giant-cell bone tumor expressing progesterone receptors may manifest benign
      behavior. Cathepsin D may be involved in tumor expansion, possibly through its
      effect on bone resorption.

PMID- 14690292
TI  - Noninvasive measurement of compartment syndrome.
AB  - This study compared the effectiveness of a commercially available invasive
      intracompartmental pressure measuring device with an investigational noninvasive
      hardness measuring device in 75 patients undergoing examination for possible
      compartment syndrome. Legs, forearms, thighs, and arms were tested. Pressure
      values and hardness ratios were compared to one another as continuous variables
      and to the clinical diagnosis of compartment syndrome as discrete variables. The
      compartment with the highest pressure reading within a limb diagnosed with
      compartment syndrome was compared to limbs without compartment syndrome. Due to
      the low specificity of the noninvasive measurement of hardness compared to the
      invasive pressure measurement (0.82 versus 0.96), this study does not support the
      use of the hardness monitor in the diagnosis of compartment syndrome.

PMID- 14690293
TI  - Comparison of different anti-inflammatory agents in suppressing the monocyte
      response to orthopedic particles.
AB  - Three different anti-inflammatory agents--diclofenac, dexamethasone, and N
      acetylcysteine--were compared to evaluate their effectiveness in suppressing
      monocyte-macrophage cell culture activation and mediator release (tumor necrosis
      factor-alpha [TNF-alpha] and interleukin-1beta [IL-1beta]) in response to
      polymethylmethacrylate particulate debris. N-acetylcysteine and diclofenac were
      most effective in suppressing TNF-alpha and IL-1beta expression by the monocyte
      macrophages. Dexamethasone reduced TNF-alpha expression but was not as effective
      suppressing IL-1beta expression. N-acetylcysteine and dexamethasone had no effect
      on cell viability whereas diclofenac at the highest concentrations decreased cell
      viabilities. N-acetylcysteine and diclofenac, but less so dexamethasone, are
      effective in suppressing wear debris-related cell activation and mediator release
      and thus potentially represent therapeutic or preventive modalities for
      periprosthetic osteolysis.

PMID- 14690294
TI  - Proximal tibia nonunion in a patient with a previous knee fusion.

PMID- 14690295
TI  - Collagenous fibroma (desmoplastic fibroblastoma) of pectoralis minor muscle.

PMID- 14690296
TI  - Aneurysmal bone cyst of the thumb metacarpal: en-block resection and free toe
      phalanx transplantation.

PMID- 14690297
TI  - Proximal dissection of a popliteal cyst with sciatic nerve compression.

PMID- 14690298
TI  - Osteomyelitis of the pubic symphysis.

PMID- 14690299
TI  - Joint arthroplasty registries: historical and current overview--the Hungarian Hip
      and Knee Registries.

PMID- 14690300
TI  - SARS 3: are we ready?

PMID- 14690301
TI  - Institute of Cancer Research.

PMID- 14690302
TI  - Relation of erythrocyte Na+-K+ ATPase activity and cholesterol and oxidative
      stress in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Diabetic patients are at high risk of atherosclerotic complications,
      and factors associated with this include hypercholesterolemia, hemorheologic
      disturbances in erythrocytes and oxidative stress. We, therefore, carried out a
      study in type 2 diabetic patients to determine the relationships of erythrocyte
      Na+-K+ ATPase activity, plasma cholesterol and oxidative stress in this
      population. METHODS: Erythrocyte Na+-K+ ATPase activity and its relationship
      between plasma cholesterol and thiobarbituric acid reactive substance (TBARS, a
      marker of oxidative stress) were studied in type 2 diabetic patients with (n =
      26) or without angiopathy (n = 30). Na+-K+ ATPase activity was measured by a
      colorimetric enzymatic method. Plasma TBARS levels were determined
      spectrophotometrically. Diabetic patients were classified according to plasma
      cholesterol concentrations as normo- or hypercholesterolemic (plasma total
      cholesterol > 5.18 mmol/L). RESULTS: Diabetic patients with or without angiopathy
      had lower erythrocyte Na+-K+ ATPase activity (p < 0.001 and p < 0.001
      respectively) and higher plasma TBARS levels than healthy subjects (n = 20) (p <
      0.001 and p < 0.001 respectively). Na+-K+ ATPase activity in the diabetic
      patients with angiopathy was lower than in the diabetic patients without
      angiopathy (p < 0.001). In the diabetic patients both with and without
      angiopathy, hypercholesterolemic patients had lower erythrocyte Na+-K+ ATPase
      activity and higher plasma TBARS levels than normocholesterolemic patients (p <
      0.001, p < 0.001 respectively) There was no difference in the plasma TBARS
      concentrations between diabetic patients with and without angiopathy. There were
      negative correlations between erythrocyte Na+-K+ ATPase activity and both plasma
      cholesterol (r = -0.72) and plasma TBARS (r = -0.46) and a positive correlation
      between plasma cholesterol and TBARS (r = 0.42). CONCLUSIONS: Elevated plasma
      cholesterol may be responsible for the inhibition of erythrocyte Na+-K+ ATPase
      activity. Together with elevated cholesterol, free radical-induced mechanisms may
      be involved in the inhibition of Na+-K+ ATPase activity.

PMID- 14690303
TI  - Genetic analysis of psychiatric disorders associated with human chromosome 18.
AB  - Current models on the etiology of psychiatric disorders support the idea of a
      biologic cause as well as interactions of biologic systems with the environment.
      The elucidation of the genetic etiology is of paramount importance to understand
      the cause of psychiatric disorders. Human chromosome 18 was identified as one of
      the first chromosomes to be aberrant in psychiatric patients and has subsequently
      served as a model to identify the molecular cause. In this article I review a
      multitude of methodologies that can be used in determining the genetic basis of
      schizophrenia, affective disorder and autism associated with human chromosome 18.
      These strategies include the use of chromosome aberrations, linkage and
      association studies, mouse-human comparative genomics, mutation analysis on
      candidate genes, trinucleotide repeat expansion studies, search for genes
      demonstrating parental effects and bioinformatics. Current data from the use of
      these methods are cited from the literature. Linkage and association studies have
      suggested at least 2 candidate loci on the short and long arms of chromosome 18
      for each of these psychiatric disorders. Some loci are supported by the mapping
      of chromosome aberrations from psychiatric patients. Mutation analyses of
      psychiatric patients with 4 candidate genes (NEDD4L, IMPA2, PACAP and GNAL)
      mapping within these loci have been unsuccessful, although an association was
      found with the IMPA2 gene in patients with schizophrenia. With these methods and
      findings, our understanding of the cause of psychiatric disorders associated with
      human chromosome 18 has improved and will advance, especially with emerging data
      from the human and rodent genome projects.

PMID- 14690304
TI  - Inflammatory bowel disease: Crohn's disease and the success of NODern genetics.
AB  - The inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis,
      are multifactorial in etiology, but a major causative role for genetic factors
      has long been recognized. Recent advances in genetic technologies have made
      dissection of the genes underlying common diseases possible; consequently, there
      is an emerging understanding of the inherited factors that predispose to IBD. In
      this review, we summarize current information on the genetics of IBD, emphasizing
      the discovery of CARD15 variants as susceptibility alleles for Crohn's disease
      and the impact of this discovery on patient care and in delineating pathogenesis
      of this complex disease.

PMID- 14690305
TI  - Academic health leadership: looking to the future. Proceedings of a workshop held
      at the Canadian Institute of Academic Medicine meeting Quebec, Que., Canada, Apr.
      25 and 26, 2003.
AB  - The academic health sector will face major changes in governance, health care
      delivery, educational requirements and research programs over the next decade.
      Increased emphasis on disease prevention and health outcomes, the need for
      evidence to support both clinical and policy decisions, educational changes both
      in content and delivery, and the importance of working in teams will challenge
      the academic health care community. Large research teams may require new ways of
      training and nurturing young investigators, including improved grant writing and
      knowledge translation, human resource management skills and the ability to
      interact with disciplines that have different research methodologies. MD/PhD and
      Clinician Investigator Programs may help to fill these gaps in medicine, but
      nursing is faced with a serious shortage of doctoral-trained educators and
      researchers and may need targeted programs to achieve a critical mass of
      academics able to accept leadership roles. The success of the Quebec model of
      support for health research networks and researchers is encouraging. There is a
      leadership gap within health care institutions that spans jurisdictions and
      affects both institutional performance and individual careers. Young
      investigators need good mentors and adequate protected time to acquire the skills
      necessary for leadership roles. Policy changes within health care institutions
      and academic organizations will be necessary to adapt to the coming decade. The
      Canadian Institute of Academic Medicine is committed to developing better
      mentoring strategies for the next generation of academic leaders and to creating
      formal assessments of major Canadian health issues that can be used by health
      care advocacy groups when talking with policy-makers.

PMID- 14690306
TI  - Cervical cancer: an opportunity to prevent and cure.

PMID- 14690307
TI  - Cervical cytology classification and the Bethesda System.
AB  - Cervical cancer screening represents one of the great success stories in cancer
      prevention. Cervical cytology results were reported by use of various
      terminologies during the first 40 years of widespread screening. These terms did
      not correspond to current knowledge of cervical carcinogenesis. The Bethesda
      System for reporting cervical cytology was developed to provide a uniform system
      of terminology that would promote clear management guidelines. The Bethesda
      System has been widely adopted since the first workshop was convened by the
      National Cancer Institute in 1988. Two additional workshops were held in 1991 and
      2001 in order to address scientific advances and controversial areas. The 2001
      workshop was attended by more than 400 participants and was preceded by Internet
      discussion groups. Major changes include specimen adequacy designation and
      criteria, general categorization, and terminology for atypical epithelial cells.
      The "within normal limits" and "benign cellular changes" categories have been
      combined into a single category called "negative for intraepithelial lesion or
      malignancy." The "favor reactive" descriptors have been removed from the atypical
      epithelial categories, and new terms correlate better with management guidelines.
      Other changes are discussed, and a brief update of cancer screening guidelines is
      also provided.

PMID- 14690308
TI  - Pathology of cervical cancer.
AB  - Squamous cell carcinoma is the most common malignant cervical tumor, but the
      incidence of adenocarcinomas has been rising during the past few decades. This
      article discusses the epidemiology and pathogenesis of the squamous cell
      carcinoma, its clinical and histologic features, including microinvasive
      carcinoma, its histologic grade, and variant tumors. The prognostic impact of
      these features and the differential diagnosis are also covered. The second
      portion of this article is devoted to the glandular tumors of the cervix,
      including adenocarcinoma in situ and invasive adenocarcinoma and its variants.
      The differential diagnosis of these tumors with tumor like glandular lesions is
      given special attention. Finally, less common malignant cervical tumors are
      covered, with an emphasis being placed on their significance.

PMID- 14690309
TI  - The epidemiology of cervical cancer.
AB  - Cervical cancer is one of the most common neoplastic diseases affecting women,
      with a combined worldwide incidence of almost half a million new cases annually,
      second only to breast cancer. Basic and epidemiologic research conducted during
      the past 15-20 years have provided overwhelming evidence for an etiologic role
      for infection with certain types of sexually-transmitted human papillomavirus
      (HPV) as the primary cause of cervical cancer. The relative risks of cervical
      cancer following HPV infection as ascertained in case-control and cohort studies
      are among the highest in cancer epidemiology. The available evidence indicates
      that the HPV-cervical cancer association satisfies all relevant causal criteria
      for public health action. Other cervical cancer risk factors, such as smoking,
      parity, use of oral contraceptives, diet, other infections, and host
      susceptibility traits must be understood in the context of mediation of
      acquisition of HPV infection or in influencing events of the natural history of
      cervical neoplasia that occur following the establishment of a persistent HPV
      infection. Virtually all cervical carcinoma specimens contain HPV DNA, which
      suggests that HPV infection is a necessary cause of cervical neoplasia. This is
      the first instance in which a necessary cause has been demonstrated in cancer
      epidemiology--a realization that has obvious implications for primary and
      secondary prevention of this neoplastic disease.

PMID- 14690310
TI  - The virology of cervical neoplasia: an HPV-associated malignancy.
AB  - Human papillomaviruses are present in virtually all cervical cancers and cancer
      precursors. Understanding the epithelial virology of this group of viruses has
      greatly influenced current concepts of cervical carcinogenesis, has provided a
      framework for understanding the biologic basis of many diagnostic criteria, and
      has led to revised classification schemes, diagnostic testing, and modifications
      in clinical management. This paper briefly reviews virologic concepts supporting
      the pathogenetic role of these viruses in cervical neoplasia.

PMID- 14690311
TI  - Vaccines for cervical cancer.
AB  - Human papillomaviruses (HPVs) are responsible for the nearly 450,000 cervical
      cancers that occur each year throughout the world. In the United States, the
      cancer rate is low (13,500 cases per year); nevertheless, HPVs affect millions of
      men and women annually in the form of genital warts and preinvasive diseases of
      the cervix and anogenital region. The expense of cancer prevention via precancer
      and cancer management is high, yet most HPV infections resolve spontaneously as a
      result of a successful host immune response. Recently, the discovery of methods
      to reproduce HPV virions (viral-like particles) in vitro has resulted in a
      successful clinical trial of preventing HPV infection and its associated
      precursor lesions. Although prevention is type-specific and duration of immunity
      is unknown, these results validate a vaccine strategy targeting prepubertal
      children that could prevent a significant proportion of genital warts and
      cervical precancers and cancers from occurring during reproductive life.
      Reversing advanced preinvasive and invasive cervical neoplasia with
      immunotherapeutics is a more difficult challenge, inasmuch as little or no
      evidence for natural immune-mediated regression of these diseases exists.
      Nonetheless, recent controlled trials have shown some success in inducing
      precursor regression with vaccines targeting viral oncoproteins. Anecdotal
      reports of therapies that augmentcellular immunity raise hopesthattherapeutics
      targeting multiple pathways of anti-viral or anti-tumor immunity will be
      beneficial to women with established cervical cancer. However, success will
      require identifying and circumventing the mechanisms by which tumor cells evade
      the immune system.

PMID- 14690312
TI  - Management of atypical and low-grade cervical cytology.
AB  - The finding of atypical and low-grade cervical cytology on routine Papanicolaou
      test is considered problematic for gynecologists and pathologists. The
      interpretation and management of these cases can be difficult when Papanicolaou
      test results fall into the Bethesda 2001 categories of atypical squamous cells,
      atypical squamous cells--cannot rule out high-grade, atypical glandular cells, or
      low-grade squamous intraepithelial lesion. Although liquid-based Papanicolaou
      tests may have resulted in some improvement in detection, a large amount of
      variability in cytologic interpretations continues to exist. The recent approval
      of concurrent use of high-risk human papillomavirus DNA testing with cytology in
      the screening of women for cervical neoplasia adds a new dilemma to patient
      management: What should we do with women who are positive for high-risk human
      papillomavirus DNA but have negative cervical cytologic results?

PMID- 14690313
TI  - High-grade squamous intraepithelial lesions.

PMID- 14690314
TI  - Cervical cancer staging.
AB  - The "International Classification of the Stages of Carcinoma of the Uterine
      Cervix" dates back to 1950; since then, seven changes have been made to the
      staging system for cervical cancer (almost all were made to Stage I), the most
      recent being in 1995. The FIGO system of classification of cervical cancer is
      originally based on the results of clinical examination, essentially of the
      anatomical extent of disease, and is determined at the time of primary diagnosis.
      Only if the rules for clinical staging are strictly observed is it possible to
      compare results using different modalities of treatment. Cervical cancer remains
      a clinically staged malignancy according to the FIGO staging system. Surgical
      pathologic staging would not be feasible for advanced-stage disease or in early
      stage patients treated primarily with radiation, especially in nations that do
      not routinely offer surgical extirpation due to different or limited health care
      resources. However, surgical and pathological data are important for precise
      analysis of survival and prognostic risk factors.

PMID- 14690315
TI  - Stage Ia-IIa cancer of the cervix.
AB  - Early-stage cervical cancer is unique among malignancies in that two radically
      different yet equally efficacious treatments can be offered to most patients with
      the disease. The choice between surgery and radiation therapy depends on the
      patient's age and comorbidities, tumor factors, physician bias, and discussion of
      the risks and benefits of each modality. A thorough discussion between the
      physician and patient is necessary to determine the optimal management for each
      individual. This review discusses the major factors that influence physician and
      patient management choices.

PMID- 14690316
TI  - Stage IIB-IVA cancer of the cervix.
AB  - Stage IIB-IVA cancer of the cervix represents locally advanced-stage disease that
      has extended beyond the cervix without clinical evidence of extrapelvic
      metastasis. Localized surgery is seldom used as the extent of the disease
      precludes and an adequate surgical margin. Both sophisticated imaging and
      surgical staging have been utilized to accurately assess the extent of disease
      for treatment planning. Careful attention to radiation technique and the use of
      brachytherapy impact survival and treatment morbidity. Concurrent cisplatin-based
      chemotherapy has become the accepted standard based on randomized clinical trials
      (level 1 evidence). Further improvements may be achieved with combination
      chemotherapy, hyperthermia or prophylactic extended field radiation. However,
      these improvements, currently practiced in developed countries, must be
      implemented in underdeveloped countries which have the greatest burden of this
      disease.

PMID- 14690317
TI  - Pelvic exenteration and reconstruction.
AB  - For the past six decades, pelvic extenteration has been utilized in the treatment
      of localized central pelvic recurrences after chemo/radiotherapy. The radicality
      of the procedure that includes resection of the bladder, vulva/vagina, and
      rectum, although with curative intent, results in comprehensive changes for the
      patient. For this reason, all patients should undergo extensive psychosocial
      counseling to prepare them for the changes in body image and lifestyle.
      Extirpation of the pelvic viscera has undergone a number of modifications since
      Brunschwig first described it in 1948 to maximize survivability and minimized
      anatomical distortion. Most of the advancements have been focused on the
      reconstructive phase after pelvic exenteration. A few select patients can be free
      of any external appliances such as a colostomy bag with utilization of a low
      colorectal anastomosis, and can maintain sexual intimacy with creation of a
      neovagina. In addition, reconstruction of the pelvic floor with omental flaps,
      dura mater grafts and myocutaneous flaps have decreased postoperative morbidity.
      In this article, we provide a review of pelvic exenteration in gynecologic
      oncology, emphasizing preoperative evaluation, surgical techniques and their
      postoperative management.

PMID- 14690318
TI  - The role of chemotherapy in the management of carcinoma of the cervix.
AB  - Carcinoma of the cervix remains the most common form of cancer to affect women
      worldwide despite effective screening techniques. Advances in treatment,
      particularly systemic therapies, have improved outcomes for cervical cancer. This
      article examines the role of chemotherapy, particularly in those patients with
      disseminated disease and those with locally advanced disease in the pelvis.

PMID- 14690319
TI  - The concept of LET in thermoluminescence dosimetry--is it meaningful or helpful?

PMID- 14690320
TI  - Dose assessment from activated sodium within a body in criticality accidents.
AB  - Some data were derived using recent sophisticated methods to rapidly convert
      specific activity of induced 24Na to average dose over a whole body in
      criticality accidents. Monte Carlo calculations using the MCNP-4B code were
      performed to study energy spectra of neutrons and gamma rays for some criticality
      systems with fissile uranium. Absorbed dose to the human body and the activation
      of sodium were also analysed against external radiation by simulations using a
      MIRD-5 type phantom and the calculated energy spectra. It was found that the
      neutron dose assessment from induced 24Na would be important to give medical
      staff initial guidance for treatment of a victim. However, the energy
      distribution of incident neutrons to the human body did not significantly
      influence the conversion from the specific activity of 24Na to dose from gamma
      rays induced within a body. Analyses were made to clarify the dependence of
      conversion from 24Na specific activity to neutron dose on the orientation toward
      the source and the size of the human body. The total dose estimated based upon
      the obtained data ranged from 33 mGy to 514 mGy for a given specific activity of
      1.4 kBq 24Na per g 23Na for some criticality assemblies. This study suggested
      that the size of uranium solution and material around the fuel should be defined
      to properly estimate the total dose, including the dose from external photons.

PMID- 14690321
TI  - Shielding experiment of heavy-ion produced neutrons using a tissue-equivalent
      proportional counter.
AB  - A shielding experiment was performed at the HIMAC (Heavy Ion Medical Accelerator
      in Chiba), of National Institute of Radiological Sciences (NIRS), to measure
      neutron dose using a spherical TEPC (tissue-equivalent proportional counter) of
      12.55 cm inner diameter. Neutrons are produced from a 5 cm thick stopping length
      Cu target bombarded by 400 MeV/nucleon C6+ ions and penetrate concrete or iron
      shields of various thicknesses at 0 degree to the beam direction. From this
      shielding experiment. y-distribution, mean lineal energy, absorbed dose, dose
      equivalent and mean-quality factor were obtained behind the shield as a function
      of shield thickness. The neutron dose attenuation lengths were also obtained as
      126 g cm(-2) for concrete and 211 g cm(-2) for iron. The measured results were
      compared with the calculated results using the MARS Monte Carlo code.

PMID- 14690322
TI  - Study of a Greek area with enhanced indoor radon concentrations.
AB  - In this paper the focus is on Arnea Chalkidikis, an area in Greece with granitic
      geological background and indications of possible elevated radon concentration
      indoors. Data are reported of indoor radon measurements with etched track
      detectors and those are used for dosimetric estimations. Moreover, data are
      reported on soil gas and soil radon concentrations in Arnea, as well as radon and
      uranium concentrations in water samples. From the measured radon concentrations
      in water samples the contribution to the overall dose has been calculated. For a
      period of 1 month, indoor radon and progeny activity has also been monitored in
      the dwelling that has the maximum indoor radon concentration in Greece. This
      dwelling is in Arnea and the dose delivered to the inhabitants has been
      calculated. The mean annual effective dose due to indoor radon was 4.5 mSv and
      about 11% of this was due to the use of water. Mean soil gas concentration and
      soil radon concentration were (90 +/- 30) kBq m(-3) (p<0.05) and (30 +/- 5) kBq
      m(-3) (p<0.05) respectively. Mean uranium concentration of the water samples was
      (98 +/- 13) mBq l(-1) (p<0.05).

PMID- 14690323
TI  - Indoor radon survey in dwellings of nine cities in the Eastern and the Western
      provinces of Saudi Arabia.
AB  - The results of a first phase of an indoor radon survey in a total of 1610
      dwellings distributed in nine cities of the Eastern and the Western provinces of
      Saudi Arabia are presented. The objective of this radon survey was to obtain
      representative indoor radon data for seven cities in the Eastern province.
      Khafji, Hafr Al-Batin, Abqaiq, Qatif, Al-Ahsa, Dammam and Khobar and to compare
      this with two cities in the Western province, Madina and Taif. So far, detailed
      radon data is not available for Saudi Arabia: therefore, this radon survey
      provides a base line for Saudi Arabia in the Radon World Atlas. On average, 200
      indoor radon dosemeters were distributed in each city and placed for a period of
      one year starting from May 2001 to May 2002. The total number of collected
      dosemeters was 847. A total of 724 houses and 98 schools were covered in this
      survey. The results of the survey in the cities showed that the overall minimum,
      maximum and average radon concentrations were 1, 137 and 22 Bq m(-3),
      respectively. Geometric mean and geometric standard deviations of the radon
      distribution were found to be 18 and 1.92, respectively. In one of the dwellings
      in Qatif city, radon concentration, measured by a passive system and then
      confirmed by an active system, was found to be 535 +/- 23 and 523 +/- 22 Bq m(
      3), respectively. The result of a radon survey in 98 schools showed that the
      minimum, maximum and average radon concentrations were 1, 70 and 19 Bq m(-3),
      respectively. The average radon concentration for each city was also determined.
      The lowest average radon concentration (8 Bq m(-3)) was found in Al-Ahsa while
      the highest average concentration (40 Bq m(-3)) was found in Khafji.

PMID- 14690324
TI  - Recall of past use of mobile phone handsets.
AB  - Previous studies investigating health effects of mobile phones have based their
      estimation of exposure on self-reported levels of phone use. This UK validation
      study assesses the accuracy of reported voice calls made from mobile handsets.
      Data collected by postal questionnaire from 93 volunteers was compared to records
      obtained prospectively over 6 months from four network operators. Agreement was
      measured for outgoing calls using the kappa statistic, log-linear modelling,
      Spearman correlation coefficient and graphical methods. Agreement for number of
      calls gained moderate classification (kappa = 0.39) with better agreement for
      duration (kappa = 0.50). Log-linear modelling produced similar results. The
      Spearman correlation coefficient was 0.48 for number of calls and 0.60 for
      duration. Graphical agreement methods demonstrated patterns of over-reporting
      call numbers (by a factor of 1.7) and duration (by a factor of 2.8). These
      results suggest that self-reported mobile phone use may not fully represent
      patterns of actual use. This has implications for calculating exposures from
      questionnaire data.

PMID- 14690325
TI  - Radiation doses to patients from endoscopic retrograde cholangiopancreatography
      examinations and image quality considerations.
AB  - The purpose of this investigation was to measure the dose-area product (DAP) and
      the other relevant dosimetric quantities in diagnostic and therapeutic endoscopic
      retrograde cholangiopancreatography (ERCP). Furthermore, the dependence of
      patient dose and image quality on the tube potential was investigated. A DAP
      meter was used for dose monitoring in seven diagnostic and 21 therapeutic ERCPs.
      For each ERCP the DAP meter readings, fluoroscopy time, number of radiographs and
      exposure data were recorded. From these data the fluoroscopy and radiography
      contributions to DAP, the entrance skin dose and the effective dose for each
      examination were estimated. For the investigation of the effect of tube potential
      on patient dose and image quality, a water phantom containing syringes filled
      with diluted contrast media was used. The average DAP was 13.7 Gy cm2 in
      diagnostic and 41.8 Gy cm2 in therapeutic ERCP whereas the average fluoroscopy
      times were 3.1 and 6.0 min respectively. DAP was strongly correlated to the
      fluoroscopy time. Measurements in the phantom showed that a good compromise
      between image quality and patient dose is obtained for tube potentials around 80
      kV. Therapeutic ERCPs deliver on average higher doses to patients than diagnostic
      ERCPs. However, for a difficult diagnostic ERCP more patient exposure may be
      required than for a simple therapeutic ERCP.

PMID- 14690326
TI  - Measurement of the peripheral doses for linac stereotactic radiotherapy.
AB  - The purpose of this study was to establish peripheral doses during stereotactic
      treatments. The doses to different organs were measured by thermoluminescence
      dosemeters. A simple power function can describe the relationship between the
      measured peripheral dose and the distance from target. The dependence of measured
      peripheral dose at a particular point on the collimator size can also be
      described by a simple exponential function. Leakage radiation contributes very
      little to the dose, but becomes dominant at distances of more than 50 cm from the
      target. The arrangement of arcs as well as the collimator size influence the
      magnitude of the peripheral dose due to the contribution of exit dose and due to
      the increasing scattering volume of target. By changing the arc arrangement and
      using smaller collimators one can reduce the peripheral dose significantly and
      minimise the total body radiation burden.

PMID- 14690327
TI  - Energy dependence of new thermoluminescent detectors in terms of HP(10) values.
AB  - The aim of this work was to determine energy dependence characteristics in terms
      of values of the personal dose equivalent, HP(10). The following types of
      thermoluminescent detectors (TLDs) were investigated: (a) two new types based on
      lithium borate, Li2B4O7:Cu,In and Li2B4O7:Cu,In,Ag; (b) two types based on the
      highly sensitive material LiF:Mg,Cu,P, TLD-700H and GR 200A; (c) two well-known
      types of LiF:Mg,Ti detector, TLD-100 and TLD-700 and (d) highly sensitive Al2O3:C
      detectors. TLDs previously calibrated with 137Cs gamma rays were simultaneously
      irradiated with X ray beams in the range of mean energies between 33 and 116 keV.
      The irradiations were performed with detectors in polymethyl methacrylate (PMMA)
      holders placed on a 30 cm x 30 cm x 15 cm water phantom with PMMA walls (ISO
      phantom). Measured energy responses were compared with calculated data for HP(10)
      values. The results confirmed the satisfactory tissue equivalent characteristics
      of all investigated TLDs except Al2O3:C, which (due to its large energy
      dependence) is suitable for personal dosimetry only with an appropriate filter.

PMID- 14690328
TI  - A GIS-based prediction and assessment system of off-site accident consequence for
      Guangdong nuclear power plant.
AB  - GNARD (Guangdong Nuclear Accident Real-time Decision support system) is a
      decision support system for off-site emergency management in the event of an
      accidental release from the nuclear power plants located in Guangdong province,
      China. The system is capable of calculating wind field, concentrations of
      radionuclide in environmental media and radiation doses. It can also estimate the
      size of the area where protective actions should be taken and provide other
      information about population distribution and emergency facilities available in
      the area. Furthermore, the system can simulate and evaluate the effectiveness of
      countermeasures assumed and calculate averted doses by protective actions. All of
      the results can be shown and analysed on the platform of a geographical
      information system (GIS).

PMID- 14690329
TI  - Occupational and patient doses in the therapeutic cave, Tapolca (Hungary).
AB  - The radon concentration has been measured for three years in a hospital cave used
      for medical treatment of respiratory diseases. A mean value of the actual
      equilibrium factor measured in the cave in different seasons was used, different
      from the commonly used 0.4. The dose contribution to the patients and the staff
      was calculated using these data. The results of the dose assessment show that the
      staff in the hospital cave can receive doses up to the dose limit for
      occupational exposure (20 mSv y(-1)) when working 4 h per day in the cave.
      Patients receive 0.18-4.22 mSv committed effective dose during the treatment
      period depending on the exposure periods. The only solution to reduce the dose to
      the staff seems to be decreasing the time they spend underground, because
      intensive ventilation would disturb the special microclimate of the cave.

PMID- 14690330
TI  - Thermal diffusion of radon in porous media.
AB  - Based on the non-intersection model of cylindrical capillaries, the mean radius
      of the pores of some soils and building materials are estimated. In size, the
      above-mentioned radii are usually of the order of the free path of gas molecules
      at atmospheric pressure. A review of pore size distribution data also reveals
      that a large fraction of concrete pores belong to Knudsen's region. This fact
      indicates that the thermal gradient in these media must cause gas (radon)
      transport. The interpretation of the experimental data concerning the rate of
      emanation of 222Rn from a concrete-capped source subjected to a sudden increase
      in temperature is given, based on irreversible thermodynamics theory. The
      calculations given here for radon flux, caused by concentration and thermal
      gradients, are in satisfactory agreement with the experimental data. It is shown
      that thermodiffusion can significantly contribute to radon flux in concrete. The
      need to include the thermodiffusion radon flux in the radon entry model is
      discussed.

PMID- 14690331
TI  - Absorbed dose determination with plane-parallel chambers.
AB  - According to IAEA TRS 398 recommendations the determination of absorbed dose with
      plane-parallel ionisation chambers calibrated in terms of N(K,Q0) can be done
      using N(D,W,Q0) = (M(Q0)(free air)/M(Q0)(surface))
      N(K,Q0)B[(mu(en)/rho)(W,air)](free air) P(Q0). This equation takes into account
      only the scattering from the stem of the soft ionisation chamber, not the total
      scattering published in the scientific literature. That makes it difficult to
      perform dosimetry with field sizes different from those used in the
      standardisation laboratory to calibrate the chamber. This paper describes a
      method to calculate D(W,Q0) by using either N(K,Q0) or N(D,W,Q0) for different
      radiation field sizes.

PMID- 14690332
TI  - The helix-loop-helix transcription factor Id1 is highly expressed in psoriatic
      involved skin.
AB  - The helix-loop-helix transcription factor Id1 (inhibitor of
      differentiation/inhibitor of DNA binding) functions as an inhibitor of
      differentiation. We have examined Id1 gene expression in cultured keratinocytes
      in punch biopsies from psoriatic involved and uninvolved skin, and in skin
      specimens from normal individuals. Id1 mRNA expression was measured with an RNase
      protection assay and with Northern blot. Id1 immunoreactivity was determined in
      skin biopsies by immunofluorescence using a polyclonal antibody directed against
      the Id1 protein. In cultured keratinocytes, the expression of Id1 mRNA was
      strongest in small cells with high proliferative potential, whereas in large
      cells, which are terminally differentiated, the expression was low. Expression of
      the Id1 mRNA in psoriatic involved skin (n = 9) was significantly elevated
      compared to uninvolved skin from the same patient (n = 5) and to skin from normal
      controls (n = 9). Id1 immunoreactivity was intranuclear throughout all the layers
      in psoriatic involved epidermis, except in the stratum corneum, while no
      immunoreactivity was detected in uninvolved epidermis. In normal controls,
      cytoplasmatic Id1 immunoreactivity was detected in the basal layer in epidermis
      obtained from newborns, while no immunoreactivity was detected in epidermis
      obtained from the adults in the control group. We conclude that Id1 is expressed
      in cells with high proliferative potential, and is downregulated in cells that
      undergo terminal differentiation. Along with the overexpression of the Id1 gene
      in psoriatic involved skin, these observations suggest that Id1 is involved in
      the process of differentiation of keratinocytes seen in normal skin and that the
      Id1 pathway is activated in psoriasis.

PMID- 14690333
TI  - Epidermal thickness at different body sites: relationship to age, gender,
      pigmentation, blood content, skin type and smoking habits.
AB  - Epidermal thickness and its relationship to age, gender, skin type, pigmentation,
      blood content, smoking habits and body site is important in dermatologic research
      and was investigated in this study. Biopsies from three different body sites of
      71 human volunteers were obtained, and thickness of the stratum corneum and
      cellular epidermis was measured microscopically using a preparation technique
      preventing tissue damage. Multiple regressions analysis was used to evaluate the
      effect of the various factors independently of each other. Mean (SD) thickness of
      the stratum corneum was 18.3 (4.9) microm at the dorsal aspect of the forearm,
      11.0 (2.2) microm at the shoulder and 14.9 (3.4) microm at the buttock.
      Corresponding values for the cellular epidermis were 56.6 (11.5) microm, 70.3
      (13.6) microm and 81.5 (15.7) microm, respectively. Body site largely explains
      the variation in epidermal thickness, but also a significant individual variation
      was observed. Thickness of the stratum corneum correlated positively to
      pigmentation (p = 0.0008) and negatively to the number of years of smoking (p <
      0.0001). Thickness of the cellular epidermis correlated positively to blood
      content (P = 0.028) and was greater in males than in females (P < 0.0001).
      Epidermal thickness was not correlated to age or skin type.

PMID- 14690334
TI  - Defective cyclic guanosine monophosphate-gated calcium channels and the
      pathogenesis of psoriasis.
AB  - A positive association between intake of calcium channel blockers and psoriasis
      has been observed recently. Intake of blockers of voltage-gated calcium ion
      channels is associated with outbreaks of psoriasis after a latent period in
      patients with and without a previous family history of psoriasis. This suggests
      that interfering with calcium influx may trigger psoriasis. Calcium influx also
      occurs via cyclic guanosine monophosphate-gated channels; human keratinocytes
      contain functional and non-functional (splice variants) versions of these
      channels. We show here that keratinocytes and skin from psoriatic individuals
      express higher levels of mRNA encoding a non-functional cyclic guanosine
      monophosphate-gated calcium channel and that high expression of the splice
      variant by transfection of cells in culture leads to loss of protein expression
      for the functional cyclic guanosine monophosphate-gated Ca2+ channels.

PMID- 14690335
TI  - Effect of pregnancy and menopause on facial wrinkling in women.
AB  - Women appear to be at greater risk of developing wrinkles with age than men. To
      evaluate the effect of pregnancy and menopause on facial wrinkling, a total of
      186 Korean women volunteers aged between 20 and 89 years were interviewed for
      information on menstrual and reproductive factors. An 8-point photographic scale
      developed for assessing the severity of wrinkles in Asian skin was used.
      Cumulative sun exposure, both occupational and recreational, was estimated. In
      Korean women, the risk of facial wrinkling increases significantly with
      increasing number of full-term pregnancies (OR = 1.835, 95% confidence interval
      (CI) 1.017-3.314) and menopausal age (number of years since menopause) (OR =
      3.909, 95% CI 1.071-14.275), while hormone replacement therapy is associated with
      a significantly lower risk for the development of facial wrinkling in
      postmenopausal women (OR = 0.221, 95% CI 0.047-0.949). Hypo-oestrogenism may play
      a part in the decrease of skin collagen leading to skin wrinkling in
      postmenopausal women.

PMID- 14690336
TI  - Gluten-free diet in psoriasis patients with antibodies to gliadin results in
      decreased expression of tissue transglutaminase and fewer Ki67+ cells in the
      dermis.
AB  - Previous studies have shown that 16% of patients with psoriasis vulgaris have IgA
      and/or IgG antibodies to gliadin, but few have antibodies to endomysium. The
      increase in duodenal intraepithelial lymphocytes was mild. Still, highly
      significant clinical improvement was observed after 3 months on a gluten-free
      diet. This study surveys certain immunohistological aspects of involved and non
      involved skin in 28 AGA-positive psoriasis patients before and after 3 months of
      a gluten-free diet. Staining was performed for CD4+ T lymphocytes, Langerhans'
      cells, endothelium, proliferating (Ki67) cells and tissue transglutaminase. In
      the entire group of patients, as well as in those on a gluten-free diet as the
      only treatment, Ki67 + cells in involved dermis were highly significantly
      decreased after the diet. There was a significant decrease in Ki67 + cells even
      in patients without increased intraepithelial lymphocytes. Tissue
      transglutaminase was highly overexpressed in involved skin in the papillary
      endothelium, and decreased by 50% after gluten-free diet. The possible role of
      tissue transglutaminase in the pathogenesis of psoriasis needs further
      investigation.

PMID- 14690337
TI  - High-dose intravenous immunoglobulin for severe drug reactions: efficacy in toxic
      epidermal necrolysis.
AB  - High-dose intravenous immunoglobulin has been proposed as an alternative
      treatment for several immuno-mediated inflammatory skin diseases, usually at a
      dosage of 1 - 2 g/kg. We describe the treatment of 10 patients affected by toxic
      epidermal necrolysis using 400 mg/kg per day on 5 consecutive days--a schedule
      that is lower than previously reported schedules. According to the SCORTEN, the
      earlier predicted mortality rate was 35%. After high-dose intravenous
      immunoglobulin therapy, a mortality rate of 10% and a survival rate of 90% were
      reached. In particular, nine patients showed a dramatic improvement already after
      one course of infusion started at an early stage of the disease. It is our
      experience, and that of others, that high-dose intravenous immunoglobulin can be
      considered the drug of first choice for toxic epidermal necrolysis, one of the
      most severe life-threatening dermatological conditions, and a valid alternative
      therapy for different long-standing chronic dermatological diseases. This therapy
      can also be effective in avoiding high steroid dosages and consequently steroid
      related or immunosuppressive-related side effects. It is therefore reasonable to
      propose high-dose intravenous immunoglobulin treatment as a valuable therapeutic
      tool for dermatologists.

PMID- 14690338
TI  - Adjunctive high-dose intravenous immunoglobulin treatment for resistant atopic
      dermatitis: efficacy and effects on intracellular cytokine levels and CD4 counts.
AB  - Although atopic dermatitis generally responds to topical therapy, small numbers
      of patients have severe resistant disease despite second-line therapies. High
      dose intravenous immunoglobulin has been suggested to be of benefit in a small
      number of reports. We have conducted an open, single-centre study of adjunctive
      high-dose intravenous immunoglobulin (Flebogamma 5%). Six patients received
      treatment at 2 g kg(-1) month(-1) for 6 cycles, with a 3-month follow-up period.
      Skin scores, lymphocyte phenotypes and intracellular cytokine analysis were
      performed. Four of six patients had major improvements in skin scores and the
      overall reduction was significant (p = 0.035). CD4+ T-cell numbers fell following
      high-dose intravenous immunoglobulin infusions, recovering by the next cycle. T
      cell CD69 expression decreased to 60% of baseline values. Reductions in the
      proinflammatory cytokines IFN-gamma and TNF-alpha were non-significant.
      Adjunctive high-dose intravenous immunoglobulin may be a useful therapeutic
      approach in adults with severe treatment-resistant atopic dermatitis, but it will
      require further assessment in randomized controlled trials to establish this.

PMID- 14690339
TI  - Scalp psoriasis: synergy between the Malassezia yeasts and skin irritation due to
      calcipotriol.
AB  - To investigate if there is a synergy between the presence of the Malassezia
      yeasts and the adverse reaction during treatment of scalp psoriasis with
      calcipotriol scalp solution, patients were treated with itraconazole to reduce
      the number of Malassezia yeasts. This study was a double-blind, placebo
      controlled parallel group study between oral itraconazole or placebo for 8 weeks
      in patients with scalp psoriasis. After 2 weeks, calcipotriol scalp solution was
      applied twice daily for 6 weeks. Altogether 137 patients, 67 in the itraconazole
      group and 70 in the placebo group, comprised the intention-to-treat population.
      There were 13 (19.4%) patients with local skin irritation in the itraconazole
      group compared to 33 (47.1%) in the placebo group (p < 0.001). The skin
      irritation was significantly lower in patients with a low number of cultured
      Malassezia yeasts (p = 0.017). Thus, when Malasessia was eliminated or the
      numbers reduced, the irritation produced by calcipotriol was significantly
      diminished.

PMID- 14690340
TI  - Prostacyclin reduces symptoms and sympathetic dysfunction in erythromelalgia in a
      double-blind randomized pilot study.
AB  - Sympathetic dysfunction and skin microvascular arteriovenous shunting with
      insufficient nutritive perfusion and tissue hypoxia have been reported in
      patients with erythromelalgia. The objective of this study was to determine
      whether iloprost, a synthetic prostacyclin analogue--primarily a vasodilator and
      inhibitor of platelet activation--improves symptoms and sympathetic function in
      patients with erythromelalgia. Erythromelalgia is a rare condition, but we
      managed to collect 12 primary cases for a double-blind, randomized, parallel
      group pilot trial evaluating the effect of iloprost (n = 8) and placebo (n = 4).
      The treatment effect was determined by the need for cooling of affected skin and
      by vasoconstrictor tests following Valsalva's manoeuvre and contralateral
      cooling. The results show a significant reduction in symptoms (p < 0.05) and
      sympathetic dysfunction (p < 0.05) in the iloprost group. Further studies with
      oral prostacyclins or analogues are suggested.

PMID- 14690341
TI  - Atopic dermatitis is increased following vaccination for measles, mumps and
      rubella or measles infection.
AB  - The prevalence of atopic dermatitis increased markedly in the period 1960s to the
      1990s. Earlier findings indicate that infections acquired in early life enhance
      or suppress the expression of atopic disease as a result of a change in immune
      reactivity. Our objectives were to examine the association between measles, mumps
      and rubella vaccination, measles infection and the risk of atopic dermatitis. A
      random sample of 9,744 children were followed up from birth to 3-15 years. Their
      parents responded to a questionnaire including highly structured questions on
      atopic dermatitis, measles, mumps and rubella vaccination and measles infection.
      Information on parental educational level was obtained from Statistics Denmark.
      The cumulative incidence of atopic dermatitis at age 14 was 19.7%. The confounder
      adjusted incidence ratio of atopic dermatitis among measles, mumps and rubella
      vaccinated children versus children not subjected to measles, mumps and rubella
      vaccination and measles infection was 1.86 (95% CI 1.25-2.79); the incidence
      ratio for measles-infected children was similar. The incidence of atopic
      dermatitis increased after measles, mumps and rubella vaccination and measles
      infection, which is surprising in view of the hygiene hypothesis. We suggest
      further study of the possible short-term and long-term effects of virus and
      bacteria on the immune responses and expression of atopic disease.

PMID- 14690342
TI  - Juvenile mycosis fungoides diagnosed before 18 years of age.
AB  - The literature regarding mycosis fungoides in children is sparse. To shed further
      light on the characteristics of mycosis fungoides in the paediatric population we
      analysed the clinicopathological features of 10 patients in whom this malignancy
      was diagnosed before the age of 18 years. All were Jews and Arabs with
      histologically proven patch/early plaque stage disease: 4 in stage IA, 4 in IB
      and 2 with unilesional disease. Seven patients had hypopigmented lesions either
      constituting the sole manifestation (2 patients) or in combination with classic
      lesions (5 patients); of these, 3 had light skin and 4 pigmented skin. Most
      patients had immunohistochemical features characteristic of mycosis fungoides,
      with a predominance of CD4+ T cells. Some had deletion of CD7+ cells. In 3
      patients, however, the epidermotropic cells were exclusively or predominantly
      CD8+ cells. All patients responded to conventional therapy and during an average
      follow-up of 3.4 years only one patient showed stage progression, but without
      extracutaneous involvement. It is concluded that juvenile mycosis fungoides is
      characterized by early stage disease, occasionally with unilesional disease,
      usually with hypopigmented lesions irrespective of skin colour, and a good
      response to therapy. On the basis of our experience and review of the literature,
      it appears that the CD8+ phenotype is over-represented in juvenile disease.

PMID- 14690343
TI  - Widespread livedoid vasculopathy.
AB  - A 37-year-old woman with a 13-year history of widespread livedo reticularis and
      recurrent, painful ulcerative skin lesions was referred to our department because
      of a relapse of cutaneous manifestations of the skin lesions involving almost the
      whole body surface; malar erythema and oedema, non-scarring alopecia and fever
      were also associated. Routine laboratory data, immunological investigations and
      coagulation parameters were normal or negative. Histology was consistent with
      livedoid vasculopathy. A good clinical response was obtained using intravenous
      methylprednisolone combined with pentoxifylline. Livedoid vasculopathy is a rare,
      distinctive dermatosis that can be associated with systemic autoimmune disorders
      or present in an "idiopathic" form. The latter is at present regarded as a non
      inflammatory thrombotic disease that may occur in patients with coagulation
      abnormalities. It is noteworthy that, in the present case, despite long-standing
      and dramatic cutaneous features, serious systemic complications have not
      developed and the patient's seroimmunologic and coagulative profile has remained
      normal.

PMID- 14690344
TI  - Secondary anetoderma following molluscum contagiosum infection.

PMID- 14690345
TI  - Treatment of panniculitis associated with alpha-1-antitrypsin deficiency with
      alpha-1-protease inhibitor.

PMID- 14690346
TI  - Cutaneous manifestations in male anorexia nervosa: four cases.

PMID- 14690347
TI  - Parietal/occipital ratio of the hair diameter as a measure of baldness severity
      in men.

PMID- 14690348
TI  - Vesicant-type reaction due to docetaxel extravasation.

PMID- 14690349
TI  - Recurrent aphthous stomatitis and atopy.

PMID- 14690350
TI  - Causes of death among male veterans who received residential treatment for PTSD.
AB  - Previous studies have shown elevated mortality among psychiatric and substance
      abusing patients, including veterans with PTSD. Although early studies showed
      elevated deaths from external causes among Vietnam veterans in the early postwar
      years, more recent studies have also shown increased health problems among
      veterans with PTSD. This study compared mortality due to behavioral causes versus
      other diseases among 1,866 male veterans treated for PTSD. Death certificates
      obtained for 110 veterans indicated behavioral causes accounted for 62.4% of
      deaths, standardized mortality ratio = 3.4-5.5, including accidents (29.4%),
      chronic substance abuse (14.7%), and intentional death by suicide, homicide, or
      police (13.8%). Results suggest possible opportunities to improve outcomes of
      this at-risk patient population through harm reduction interventions and improved
      continuity of care.

PMID- 14690351
TI  - A descriptive analysis of PTSD chronicity in Vietnam veterans.
AB  - This study examined the chronicity of PTSD in 530 male and female Vietnam
      veterans who were drawn from 2 large, ethnically diverse samples. Delayed onset
      was common, as was a failure to fully remit: 78% of the 239 veterans with full or
      partial lifetime PTSD were symptomatic in the 3 months prior to assessment.
      Cluster analysis identified 4 subtypes of posttraumatic response, with women most
      likely to be in a delayed onset cluster, and minority men most likely to be in a
      severe chronic cluster. The extent of chronicity observed in this sample
      underscores the need for treatments that address the persistence of posttraumatic
      symptoms.

PMID- 14690352
TI  - Do patients drop out prematurely from exposure therapy for PTSD?
AB  - Many studies have demonstrated the efficacy of exposure therapy in the treatment
      of chronic post-traumatic stress disorder (PTSD). Despite the convincing outcome
      literature, a concern that this treatment may exacerbate symptoms and lead to
      premature dropout has been voiced on the basis of a few reports. In this paper,
      we examined the hypothesis that treatments that include exposure will be
      associated with a higher dropout rate than treatments that do not include
      exposure. A literature search identified 25 controlled studies of cognitive
      behavioral treatment for PTSD that included data on dropout. The results
      indicated no difference in dropout rates among exposure therapy, cognitive
      therapy, stress inoculation training, and EMDR. These findings are consistent
      with previous research about the tolerability of exposure therapy.

PMID- 14690353
TI  - Peritraumatic versus persistent dissociation in acute stress disorder.
AB  - The DSM-IV definition of acute stress disorder (ASD) regards dissociation that
      occurs during a trauma (peritraumatic dissociation) comparably to persistent
      dissociation. This study investigated the relative contributions of peritraumatic
      dissociation and persistent dissociation to acute posttraumatic stress reactions.
      Civilian trauma (N = 53) survivors with either acute stress disorder (ASD),
      subclinical ASD, or no ASD were administered modified versions of the
      Peritraumatic Dissociative Experiences Questionnaire that indexed both
      dissociation during the trauma and dissociation at the time of assessment.
      Persistent dissociation was more strongly associated with ASD severity and
      intrusive symptoms than peritraumatic dissociation. These results are consistent
      with the proposition that persistent, rather than peritraumatic, dissociation is
      associated with posttraumatic psychopathology.

PMID- 14690354
TI  - Effects of trauma-focused research on recent domestic violence survivors.
AB  - This study investigated the impact of trauma-focused research on domestic
      violence survivors. At the end of a survey assessing psychological distress,
      abuse severity, coping self-efficacy (CSE), and cognitions, questionnaire items
      were utilized to assess participants' levels of gain, unexpected upset, and
      regret of participation. Participants were 55 women who had recently experienced
      abuse by a partner. Forty-five percent reported positive gain from participation,
      25% reported they were more upset than anticipated, and a minority of women (6%)
      expressed regret for participation. Results indicated that women who were more
      upset than expected scored significantly higher on depression, PTSD, and number
      of lifetime traumas, and significantly lower on CSE. Implications for enhancement
      of consent form documents and debriefing procedures are addressed.

PMID- 14690355
TI  - Comment on Hembree and Foa (2003) and EMDR.

PMID- 14690356
TI  - Long-term effects of the Dresden bombing: relationships to control beliefs,
      religious belief, and personal growth.
AB  - Aftereffects of the Dresden bombing of February 1945 on 47 survivors were
      investigated using a comprehensive framework of trauma sequelae including
      pathogenetic, salutogenetic, and further mediating or moderating variables. A
      relatively low rate of PTSD symptomatology was noted. Traumatic exposure was
      related to current PTSD symptoms and to personal growth, with no systematic
      relationships between the 2 outcome variables. PTSD symptoms were primarily
      related to external control, whereas personal growth was primarily associated
      with internal control. Religious belief in the afterlife moderated effects
      between exposure and posttraumatic avoidance or personal growth. Furthermore,
      belonging to particular age groups at traumatization (adolescents, middle-aged
      adults) was associated with increased posttraumatic intrusions at the time of
      data collection.

PMID- 14690357
TI  - Stress reactions among Swedish peacekeeping soldiers serving in Bosnia: a
      longitudinal study.
AB  - Assessments of mental health (GHQ-28) were performed on a Swedish battalion
      serving in Bosnia at 4 times: before deployment, immediately after deployment, 6
      months after deployment, and 1 year after deployment. Complete responses were
      obtained from 316 participants (61% response rate). No significant change of
      mental health over time was noted. Individuals having experienced traumatic
      events in Bosnia, as well as stressful life events postdeployment, reported the
      poorest mental health. Logistic regression analysis showed that postdeployment
      stressors made the strongest contribution to registering a poor mental health
      score after one year.

PMID- 14690358
TI  - Health effects of war stress on Norwegian World War II resistance groups: a
      comparative study.
AB  - The main aim of this study was to investigate the extent to which adverse long
      term health effects of World War II stress exposure were present in 3 groups of
      resistance veterans. The groups had been exposed to different types of war
      stressors: concentration camp incarceration, resistance participation within the
      illegal press, and a secret military organization. With the differences in war
      stressors as a basis, we assumed that those incarcerated in a concentration camp
      would display more adverse health effect compared to the resistance veterans. The
      findings point to a relationship between the severity of war stressors and
      postwar health in all 3 groups.

PMID- 14690359
TI  - Positive adaptation to trauma: wisdom as both process and outcome.
AB  - Positive adaptation to psychological trauma and wisdom both have a rich history
      in European literature and philosophy. Although the literature on posttraumatic
      growth has recognized the possibility of wisdom as an outcome of adaptation, its
      role in the process of adaptation has been neglected. A theoretical framework is
      presented that conceptualizes three dimensions of wisdom as crucial to an
      understanding of the role it can play in posttraumatic positive adaptation. These
      dimensions are the recognition and management of uncertainty; the integration of
      affect and cognition; and the recognition and acceptance of human limitation. The
      role of these dimensions in the process and outcome of traumatic adaptation is
      considered, together with limitations of the framework and directions for future
      research.

PMID- 14690360
TI  - Predictors of nonpathological dissociation in Northern Ireland: the affects of
      trauma and exposure to political violence.
AB  - Recent work has identified an empirical distinction between pathological and
      nonpathological dissociation. This study examined the correlates of
      nonpathological dissociation in a Northern Irish sample. The Dissociative
      Experiences Scale, the Traumatic Experiences Checklist, the Guilt Inventory, and
      the General Health Questionnaire, as well as two open-ended questions assessing
      exposure to political violence were completed by 119 participants.
      Nonpathological dissociation was predicted by age, perceived impact of traumatic
      events, and adherence to moral standards. Moreover, dissociation was found to be
      significantly higher in those exposed directly to political violence and those
      experiencing childhood emotional abuse. Results are consistent with previous
      theoretical and empirical work and it is proposed that nonpathological
      dissociation is related to traumatic experience in Northern Ireland.

PMID- 14690361
TI  - Molecular structures of fructans from Agave tequilana Weber var. azul.
AB  - Agave plants utilize crassulacean acid metabolism (CAM) for CO(2) fixation.
      Fructans are the principal photosynthetic products generated by agave plants.
      These carbohydrates are fructose-bound polymers frequently with a single glucose
      moiety. Agave tequilana Weber var. azul is an economically important CAM species
      not only because it is the sole plant allowed for tequila production but because
      it is a potential source of prebiotics. Because of the large amounts of
      carbohydrates in A. tequilana, in this study the molecular structures of its
      fructans were determined by fructan derivatization for linkage analysis coupled
      with gas chromatography-mass spectrometry (GC-MS), nuclear magnetic resonance
      (NMR), and matrix-assisted laser desorption time-of-flight mass spectrometry
      (MALDI-TOF-MS). Fructans were extracted from 8-year-old A. tequilana plants. The
      linkage types present in fructans from A. tequilana were determined by
      permethylation followed by reductive cleavage, acetylation, and finally GC-MS
      analysis. Analysis of the degree of polymerization (DP) estimated by (1)H NMR
      integration and (13)C NMR and confirmed by MALDI-TOF-MS showed a wide DP ranging
      from 3 to 29 units. All of the analyses performed demonstrated that fructans from
      A. tequilana consist of a complex mixture of fructooligosaccharides containing
      principally beta(2 --> 1) linkages, but also beta(2 --> 6) and branch moieties
      were observed. Finally, it can be stated that fructans from A. tequilana Weber
      var. azul are not an inulin type as previously thought.

PMID- 14690362
TI  - Microwave-assisted headspace solid-phase microextraction for the analysis of
      bioemissions from Eucalyptus citriodora leaves.
AB  - Microwave-assisted headspace solid-phase microextraction (MA-HS-SPME) was
      developed as a simple and effective method for fast sampling of volatile organic
      compounds (VOCs) from Eucalyptus citriodora Hook (E. citriodora) leaves. During
      microwave heating, a simple shielding device made of aluminum foil was used to
      protect the SPME fiber from microwave irradiation while allowing the sample to be
      heated. A room temperature water bath was also used to allow microwave heating to
      be conducted in a more controlled manner. The inner heating caused by microwave
      irradiation dramatically accelerated the emission of VOCs from the sample, but no
      marked change in headspace temperature in the sample vial was found. Under
      optimum conditions, the extraction efficiencies obtained with microwave heating
      were much higher than those obtained without microwave heating for all fibers
      used, namely, 7-microm polydimethylsiloxane (PDMS), 100-microm
      polydimethylsiloxane (PDMS), 65-microm polydimethylsiloxane/divinylbenzene
      (PDMS/DVB), and 75-microm carboxen/polydimethylsiloxane (CAR/PDMS). The
      improvement of extraction efficiency using MA-HS-SPME allowed more VOC events to
      be detected, with more balanced extraction of VOCs of lower and higher molecular
      masses. Moreover, a good linear relationship was found between sample size and GC
      FID response (total peak area of VOCs), indicating the usefulness of MA-HS-SPME
      for quantitative analysis of individual volatile compounds in E. citriodora
      leaves.

PMID- 14690363
TI  - Correlations between pulp properties of eucalyptus clones and leaf volatiles
      using automated solid-phase microextraction.
AB  - Analysis of biogenic volatile organic compounds (BVOC) of 14 Eucalyptus clones
      has been performed using an automated headspace solid-phase microextraction (HS
      SPME) coupled to gas chromatography (GC)/ion trap mass spectrometry (ITMS)
      method. Correlations between pulp properties of Eucalyptus clones and the BVOC of
      their leaf headspaces were studied. The compounds alpha-terpineol and the
      sesquiterpene beta-eudesmol were positively correlated with S5, a property
      related to the hemicelluose content in the pulp. Qualitative results obtained
      with automated HS-SPME were sufficient to group together the same species and
      related hybrids through cluster analysis and were confirmed through principal
      component analysis. A preliminary separation of the essential oils of Eucalyptus
      dunnii through comprehensive two-dimensional gas chromatography (GC x GC) showed
      approximately 580 peaks compared to approximately 60 in a typical GC/ITMS first
      dimension chromatogram. The potential of HS-SPME coupled to GC x GC to improve
      the separation of Eucalyptus volatiles and other plant essential oils looks
      extremely promising for new applications of unsupervised learning methods.

PMID- 14690364
TI  - Development of a microtiter plate ELISA and a dipstick ELISA for the
      determination of the organophosphorus insecticide fenthion.
AB  - In previous studies, polyclonal antibodies against the organophosphorus
      insecticide fenthion were obtained and an indirect competitive enzyme-linked
      immunosorbent assay (ELISA) was developed for this pesticide. In this study,
      using these antibodies and an enzyme tracer, direct competitive ELISAs for
      fenthion in microtiter plate and dipstick formats were developed. The microtiter
      plate ELISA showed an IC(50) value of 1.2 microg/L with a detection limit of 0.1
      microg/L. The antibodies showed negligible cross-reactivity with other
      organophosphorus pesticides. The use of the dipstick format using Immunodyne as a
      support membrane allowed the quick visual detection of fenthion in concentrations
      >10 microg/L. The IC(50) value of the dipstick format using reflectance detection
      was 15 microg/L with a detection limit of 0.5 microg/L. The recoveries of
      fenthion from spiked vegetable samples using the two formats without any prior
      enrichment or cleanup steps were 87-116%.

PMID- 14690365
TI  - Solid-phase microextraction and gas chromatography olfactometry analysis of
      successively diluted samples. A new approach of the aroma extract dilution
      analysis applied to the characterization of wine aroma.
AB  - The relationship between the composition and the aroma of the wine can be
      established by using gas chromatography with olfactometric detection (sniffing or
      GCO), which combines the chromatographic response with the human nose response.
      To evaluate the contribution of the odor compounds in wine aroma, we designed a
      new approach of the aroma extract dilution analysis (AEDA) that lies in the GCO
      analysis of serially diluted wine samples using headspace solid-phase
      microextraction (HS-SPME) as the extraction technique. The fiber coating used was
      Flex divinyl-carboxen-polydimethylsiloxane. The method developed was applied to
      determine the aromatic composition of a red Grenache wine from Priorat (Spain).
      The method allows 38 important odorants to be determined in the AEDA study, 30 of
      them precisely identified. These results are similar to those reported by other
      studies related to this variety of wine. HS-SPME is a suitable technique to
      obtain representative extracts of wine aroma with several advantages such as
      simplicity, speediness, and little sample manipulation.

PMID- 14690366
TI  - A new LC/MS-method for the quantitation of acrylamide based on a stable isotope
      dilution assay and derivatization with 2-mercaptobenzoic acid. Comparison with
      two GC/MS methods.
AB  - Acrylamide (AA) was found to form a stable thioether in reasonable yields (45
      50%) when reacted with 2-mercaptobenzoic acid at 20 degrees C for 3 h. On the
      basis of this finding and using [(13)C(3)]-acrylamide as the internal standard, a
      sensitive and selective new stable isotope dilution analysis for AA quantitation
      in food samples was developed based on single stage LC/MS. Comparison of the
      quantitative results obtained by applying the new method to potato chips,
      crispbread or butter cookies with data obtained by two stable isotope dilution
      analysis, using direct measurement of AA by GC/MS, but differing in the workup
      procedure, revealed detection limits in the same order of magnitude (6.6
      microg/kg). Quantitative data obtained by application of the three methods on the
      same samples of potato chips or cookies, respectively, were also in very good
      agreement. Quantitation of AA in crispbreads treated with an amylase/protease
      mixture did not show increased AA levels, thereby indicating that inclusion of AA
      in starch/protein gels is not very probable during breadmaking.

PMID- 14690367
TI  - Determination of total folate in plant material by chemical conversion into para
      aminobenzoic acid followed by high performance liquid chromatography combined
      with on-line postcolumn derivatization and fluorescence detection.
AB  - A procedure involving chemical conversion of all forms of folate present in plant
      material into para-aminobenzoic acid (PABA) and a liquid chromatographic
      fluorimetric determination with on-line postcolumn derivatization is reported.
      All folates are cleaved with liberation of PABA by hydrogen peroxide followed by
      acid hydrolysis using concentrated hydrochloric acid (37%) at 110 degrees C for 6
      h. The reaction yield for individual folates conversion to PABA ranged from 44.4
      to 97.3%. PABA could be determined sensitively by on-line postcolumn
      derivatization with fluorescamine, the detection limit for PABA being 3.02 nM. On
      the basis of this principle, a method for the determination of total folate in
      plant material, including a purification step on an affinity column, is
      presented, which offers a sufficient sensitivity and selectivity for routine
      analysis of total folate in natural samples. The total folate contents of
      tomatoes, carrots, white cabbage, and spinach were determined, and the results
      were quite comparable to the data reported. The recovery of PABA and the
      comparison of total folate analysis in spinach on different occasions (over 6
      months) are also reported. The method is reliable, universal for all folates,
      including polyglutamate and monoglutamate forms, and eliminates the need for a
      deconjugation step and multiple conversion reactions.

PMID- 14690368
TI  - Antioxidant activity of extracts, condensed tannin fractions, and pure flavonoids
      from Phaseolus vulgaris L. seed coat color genotypes.
AB  - Twelve different seed coat color genotypes of Phaseolus vulgaris L. were
      extracted and pure flavonoids isolated from 10 of these. The seed coat methanol
      extracts, tannin fractions, and pure flavonoids all displayed antioxidant
      activity in a fluorescence-based liposome assay. The relatively high activity of
      the condensed tannin (proanthocyanidin) fractions indicates that these may play
      an important role in the overall activity of the extracts. This activity also
      indicates that although these polyphenols cause problems in digestibility, they
      may be important dietary supplements with beneficial health effects. The pure
      anthocyanins delphinidin 3-O-glucoside (1), petunidin 3-O-glucoside (2), and
      malvidin 3-O-glucoside (3) and the flavonol quercetin 3-O-glucoside (4) isolated
      from seed coats also had significantly higher antioxidant activity than the
      Fe(2+) control. The activity of kaempferol 3-O-glucoside (5) was not different
      from that of the Fe(2+) control. These findings suggest that variously colored
      dry beans may be an important source of dietary antioxidants.

PMID- 14690369
TI  - Characterization of metabolites of hydroxycinnamates in the in vitro model of
      human small intestinal epithelium caco-2 cells.
AB  - Hydroxycinnamic acids are antioxidant phenolic compounds which are widespread in
      plant foods, contribute significantly to total polyphenol intakes, and are
      absorbed by humans. The extent of their putative health benefit in vivo depends
      largely on their bioavailability. However, the mechanisms of absorption and
      metabolism of these phenolic compounds have not been described. In this study, we
      used the in vitro Caco-2 model of human small intestinal epithelium to
      investigate the metabolism of the major dietary hydroxycinnamates (ferulate,
      sinapate, p-coumarate, and caffeate) and of diferulates. The appearance of
      metabolites in the medium versus time was monitored, and the various conjugates
      and derivatives produced were identified by HPLC-DAD, LC/MS, and enzyme treatment
      with beta-glucuronidase or sulfatase. Enterocyte-like differentiated Caco-2 cells
      have extra- and intracellular esterases able to de-esterify hydroxycinnamate and
      diferulate esters. In addition, intracellular UDP-glucuronosyltransferases and
      sulfotransferases existing in Caco-2 cells are able to form the sulfate and the
      glucuronide conjugates of methyl ferulate, methyl sinapate, methyl caffeate, and
      methyl p-coumarate. However, only the sulfate conjugates of the free acids,
      ferulic acid, sinapic acid, and p-coumaric acid, were detected after 24 h. The O
      methylated derivatives, ferulic and isoferulic acid, were the only metabolites
      detected following incubation of Caco-2 cells with caffeic acid. These results
      show that the in vitro model system differentiated Caco-2 cells have the capacity
      to metabolize dietary hydroxycinnamates, including various phase I (de
      esterification) and phase II (glucuronidation, sulfation, and O-methylation)
      reactions, and suggests that the human small intestinal epithelium plays a role
      in the metabolism and bioavailability of these phenolic compounds.

PMID- 14690370
TI  - Inhibition of reactive nitrogen species effects in vitro and in vivo by
      isoflavones and soy-based food extracts.
AB  - Recent studies have shown that soy isoflavone inhibits inducible nitric oxide
      (NO) synthase activities and is reported to have peroxynitrite scavenging
      ability. Consequently, we investigated whether isoflavones (daidzein and
      genistein) and extracts from soy-based products (miso, soymilk, tofu, soy sprout,
      black soybean, soybean, and yuba) would inhibit the reactive nitrogen species
      (RNS) effect in vitro and in vivo. In the in vitro experiments [including the
      protection of cellular DNA from peroxynitrite or sodium nitroprusside damage, an
      inhibitory effect on nitric oxide production from lipopolysaccharide (LPS)
      induced RAW 264.7 cells, and nitric oxide scavenging ability], extracts from soy
      based foods showed a potent antioxidant activity and an inhibiting effect on RNS
      activity. These effects were correlated with total isoflavone content. In the in
      vivo experiments, rats were given isoflavones (4.0 mg/kg bw) or soy-based product
      extracts (1.0 g/kg bw) orally for 1 week and were injected with vehicle H(2)O (1
      mL/kg bw) or LPS (10 mg/kg bw) on the day 7. Twelve hours after treatment, the
      rats were killed, and blood serum was collected for analysis. The intraperitoneal
      administration of LPS resulted in an increase in serum nitrite, nitrate, and
      nitrotyrosine concentrations. These are stable metabolite end products of nitric
      oxide, to 4-, 16-, and 5-fold levels, (4, 10 microM and 58 +/- 14 pmol/mL), of
      the placebo control, respectively. Results showed that oral administration of
      isoflavones and extracts from soy-based products significantly decreased serum
      nitrite, nitrate, and nitrotyrosine levels in LPS-induced rats. This study
      demonstrates that soy isoflavone supplementation may inhibit RNS-induced
      oxidation both in vitro and in vivo.

PMID- 14690371
TI  - Characterization of lunasin isolated from soybean.
AB  - Lunasin is a novel and promising chemopreventive peptide from soybean. We have
      shown previously that lunasin suppresses transformation of mammalian cells caused
      by chemical carcinogens and inhibits skin carcinogenesis in mice when applied
      topically. Although the lunasin gene was cloned from soybean, all experiments
      carried out so far in our lab have used synthetic lunasin and therefore there is
      no detailed description of natural lunasin isolated from soybean. We report here
      the first characterization of soybean lunasin that includes definitive
      identification by mass peptide mapping, partial purification, and measurement of
      bioactivities of the various purified fractions and protein expression in the
      developing seed. The identity of lunasin in the seed extracts was established by
      Western blot analysis and mass spectrometric peptide mapping. All lunasin
      fractions partially purified by anion exchange and immunoaffinity column
      chromatography suppress colony formation induced by the ras-oncogene and inhibit
      core H3-histone acetylation. During seed development, lunasin peptide appears 5
      weeks after flowering and persists in the mature seed. Western blot analysis of
      different soybean varieties and commercially available soy proteins shows the
      presence of the peptide in varying amounts. These results demonstrate the
      feasibility of producing large quantities of natural lunasin from soybean for
      animal and human studies.

PMID- 14690372
TI  - Inhibitory effect of caffeic acid phenethyl ester on angiogenesis, tumor
      invasion, and metastasis.
AB  - Caffeic acid phenethyl ester (CAPE) derived from honeybee propolis has been used
      as a folk medicine and has several proven biological activities. The present
      study investigated the effect of CAPE on angiogenesis, tumor invasion, and
      metastasis. A cytotoxicity assay of CAPE in CT26 colon adenocarcinoma cells
      showed a dose-dependent decrease in cell viability but no significant influence
      on the growth of human umbilical vein epithelial cells (HUVEC). A low
      concentration of CAPE (1.5 microg/mL) inhibited 52.7% of capillary-like tube
      formation in HUVEC culture on Matrigel. CAPE (6 microg/mL)-treated CT26 cells
      showed not only inhibited cell invasion by 47.8% but also decreased expression of
      matrix metalloproteinase (MMP)-2 and -9. Vascular endothelial growth factor
      (VEGF) production from CT26 cells was also inhibited by treatment with CAPE (6
      microg/mL). Intraperitoneal injection of CAPE (10 mg/kg/day) in BALB/c mice
      reduced the pulmonary metastatic capacity of CT26 cells accompanied with a
      decreased plasma VEGF level. CAPE treatment also prolonged the survival of mice
      implanted with CT26 cells. These results indicate that CAPE has potential as an
      antimetastatic agent.

PMID- 14690373
TI  - Oil and squalene in amaranthus grain and leaf.
AB  - Amaranthus grain of 104 genotypes from 30 species was investigated for oil and
      squalene contents and fatty acid profiles. The overall average oil content in
      Amaranthus grain was 5.0%, ranging from 1.9 to 8.7%. Squalene concentration in
      extracted oils ranged from trace to 7.3%, with an average concentration of 4.2%.
      The average contents of three major fatty acids in Amaranthus grain were 22.2,
      29.1, and 44.6% for palmitic, oleic, and linoleic, respectively. The average fat
      content in dried mature leaves of 45 Amaranthus genotypes was 1.63%, ranging from
      1.08 to 2.18%. The squalene concentration in leaf lipid extracts averaged 0.26%,
      ranging from trace to 0.77%, which is much lower than that from seeds. The major
      fatty acids of leaf extracts were linolenic, linoleic, and palmitic. Linolenic
      ranged from 56.5 to 62.0% of total fatty acids; linoleic, from 15.5 to 24.7%; and
      palmitic acid, from 13.5 to 15.5%. As for the fatty acid compositions at
      different growth stages, fatty acid content in leaf lipid was lower in mature
      leaves than in young leaves. The saturated/unsaturated ratio decreased when the
      leaf grew to maturity. Principal component analysis (PCA) was carried out on
      compositional characteristics of grain. The first two components accounted for
      70% of the total variance (38.3 and 21.7%, respectively). There was a positive
      correlation between oil content and squalene yield, and a negative correlations
      were found between linoleic and either of the other two major fatty acids,
      palmitic and oleic. The taxonomic relationship among the species was also
      elucidated by PCA.

PMID- 14690374
TI  - Supercritical carbon dioxide extraction of oil and squalene from amaranthus
      grain.
AB  - Supercritical carbon dioxide (SC CO(2)) was used for the extraction of oil and
      squalene from Amaranthus grain. Very small amounts of oil could be extracted by
      SC CO(2) from undisrupted grains, although SC CO(2) possesses higher diffusivity.
      Grinding increased the extraction rate and oil yield, and smaller particle size
      gave higher extraction rate. The oil yield and initial extraction rate increased
      linearly with the increasing SC CO(2) flow rate from 1 to 2 L/min. Increasing the
      flow rate of SC CO(2) above 2 L/min resulted in only a slight increase of oil
      yield and extraction rate. In the pressure range of 150-250 bar, extraction
      decreased with increasing temperature at a constant pressure, whereas at a
      pressure of 300 bar, the extraction yield increased with increasing temperature.
      Possible reasons for this are discussed. Effects of temperature and pressure on
      squalene yield were different from those on oil yield. A good oil yield (4.77 g
      of oil/100 g of grain) was obtained at 40 degrees C and 250 bar. The highest
      squalene yield (0.31 g of squalene/100 g of grain) and concentration (15.3% in
      extract) were obtained at 50 degrees C and 200 bar, although the oil yield under
      this condition was low (2.07 g of oil/100 g of grain). The moisture content
      within 0-10% had little influence on yields of oil and squalene at 40 degrees C
      and 250 bar. Finally, the oil yield and the squalene concentration in the
      extracts by SC CO(2) were compared to those by solvent extraction.

PMID- 14690375
TI  - Qualitative investigation on hydrothermal treatment of Hinoki (Chamaecyparis
      obtusa) bark for production of useful chemicals.
AB  - Hydrothermal treatment of an outer layer of a bark of Hinoki (Chamaecyparis
      obtusa) tree was investigated qualitatively for the possibility of utilizing
      residual forest biomass to produce valuable chemicals. Experiments were carried
      out in a semibatch reactor apparatus that allows the study of the effect of
      reaction temperatures in a single run. Gas chromatography-mass spectrometry
      analyses show the presence of useful chemicals such as furfural, aromatic
      compounds (1,3-di-tert-butyl benzene and 2,4-di-tert-butyl phenol), and fatty
      acids (myristic acid, palmitic acid, and stearic acid) in the products.

PMID- 14690376
TI  - Multiple forms of xylose reductase in Candida intermedia: comparison of their
      functional properties using quantitative structure-activity relationships, steady
      state kinetic analysis, and pH studies.
AB  - The xylose-fermenting yeast Candida intermedia produces two isoforms of xylose
      reductase: one is NADPH-dependent (monospecific xylose reductase; msXR), and
      another is shown here to prefer NADH approximately 4-fold over NADPH (dual
      specific xylose reductase; dsXR). To compare the functional properties of the
      isozymes, a steady-state kinetic analysis for the reaction d-xylose + NAD(P)H +
      H(+) <--> xylitol + NAD(P)(+) was carried out and specificity constants
      (k(cat)/K(aldehyde)) were measured for the reduction of a series of aldehydes
      differing in side-chain size as well as hydrogen-bonding capabilities with the
      substrate binding pocket of the enzyme. dsXR binds NAD(P)(+) (K(iNAD+) = 70
      microM; K(iNADP+) = 55 microM) weakly and NADH (K(i) = 8 microM) about as tightly
      as NADPH (K(i) = 14 microM). msXR shows uniform binding of NADPH and NADP(+)
      (K(iNADP+) approximately K(iNADPH) = 20 microM). A quantitative structure
      activity relationship analysis was carried out by correlating logarithmic
      k(cat)/K(aldehyde) values for dsXR with corresponding logarithmic
      k(cat)/K(aldehyde) values for msXR. This correlation is linear with a slope of
      approximately 1 (r (2) = 0.912), indicating that no isozyme-related pattern of
      substrate specificity prevails and aldehyde-binding modes are identical in both
      XR forms. Binary complexes of dsXR-NADH and msXR-NADPH show the same macroscopic
      pK of approximately 9.0-9.5, above which the activity is lost in both enzymes. A
      lower pK of 7.4 is seen for dsXR-NADPH. Specificity for NADH and greater binding
      affinity for NAD(P)H than NAD(P)(+) are thus the main features of enzymic
      function that distinguish dsXR from msXR.

PMID- 14690377
TI  - Characterization of a fusarium 2-gene cluster involved in trichothecene C-8
      modification.
AB  - The Fusarium trichothecenes T-2 toxin and deoxynivalenol (DON) are potent
      inhibitors of eukaryotic protein synthesis and are a significant agricultural
      problem. Three coregulated loci are required for T-2 toxin synthesis by Fusarium
      sporotrichioides. The core-trichothecene gene cluster consists of 12 genes (Tri3
      Tri14) while the second locus consists of a single gene (Tri101). The third locus
      was recently partially described and encodes 1-2 biosynthetic enzymes and a
      putative regulatory gene. Here, we describe a detailed characterization of this
      locus. Located adjacent to Tri1 is Tri16, which is required for esterification of
      the C-8 hydroxyl. A putative regulatory gene, also adjacent to Tri1, is not
      required for T-2 toxin synthesis. The genomic sequence of Fusarium graminearum (a
      DON producer) contains a putative functional Tri1 and a nonfunctional Tri16. The
      presence of the Tri16 pseudogene is consistent with the chemical structure of
      DON, which has a C-8 keto group rather than the C-8 ester of T-2 toxin.

PMID- 14690378
TI  - Flavoring components of raw monsooned arabica coffee and their changes during
      radiation processing.
AB  - Volatile aroma principles, nonvolatile taste constituents (caffeine and
      chlorogenic and caffeic acids), and glycosidically bound aroma compounds of
      monsooned and nonmonsooned raw arabica coffee were analyzed using gas
      chromatography-mass spectrometry (GC-MS) and high-performance liquid
      chromatography (HPLC). Among the most potent odor active constituents known to
      contribute to the aroma of the green beans, 3-isopropyl-2-methoxypyrazine, 3
      isobutyl-2-methoxypyrazine, 4-vinylguaiacol, beta-damascenone, (E)-2-nonenal,
      trans,trans-2,4-decadienal, phenylacetaldehyde, and 3-methylbutyric acid were
      detected by GC-MS in both samples. A decrease in content of methoxypyrazines and
      an increase in 4-vinylguaiacol and isoeugenol resulted in a dominant spicy note
      of monsooned coffee. These phenolic compounds exist partly as their glycosides,
      and their release from the bound precursors during monsooning accounted for their
      higher content in monsooned coffee. A considerable decrease in astringent
      chlorogenic acid as a consequence of hydrolysis to bitter caffeic acid was noted
      in monsooned coffee. Radiation processing of nonmonsooned beans at a dose of 5
      kGy resulted in an increased rate of monsooning. At this dose a quantitative
      increase in most of the aroma active components could be observed in all samples
      studied. Hydrolysis of chlorogenic acid to caffeic acid was noted in radiation
      processed monsooned coffee beans irrespective of whether the treatment was
      carried out before or after monsooning. These changes were, however, not observed
      in irradiated, nonmonsooned coffee beans, suggesting an enzymatic rather than a
      radiolytic cleavage of chlorogenic acid. A rationale behind the mechanism of
      monsooning and radiation-induced enhancement of the monsooning process is
      discussed.

PMID- 14690379
TI  - Reactions of anthocyanins and tannins in model solutions.
AB  - The reaction between procyanidin dimer Ec-EcG (B2 3'-O-gallate) and malvidin 3-O
      glucoside (Mv3glc) was studied in a model solution system at two different pH
      values, 2.0 and 3.8. Disappearance of both species was much faster at pH 3.8 than
      at pH 2.0. That of Mv3glc was increased in the presence of Ec-EcG, whereas that
      of Ec-EcG was the same in the presence or absence of the anthocyanin. Values of
      absorbance at 520 nm measured at pH 2.0 were correlated with the amount of
      residual Mv3glc. Those measured at pH 3.8 hardly changed during the incubation,
      but absorbance values at 420 and 620 nm as well as resistance to sulfite
      bleaching were much increased, confirming that Mv3glc was converted to other
      pigments. Anthocyanin-flavanol adducts were observed at both pH values, but their
      structures were different. At pH 2.0, cleavage of the procyanidin linkage
      followed by nucleophilic addition of flavanol or anthocyanin moieties led to
      (Ec)(n)-EcG and (Ec)(n)-Mv3glc, respectively. At pH 3.8, nucleophilic addition of
      Ec-EcG onto the anthocyanin yielded Mv3glc-(Ec-EcG).

PMID- 14690380
TI  - Alterations of vitamin C, total phenolics, and antioxidant capacity as affected
      by processing tomatoes to different products.
AB  - This study was conducted to investigate the antioxidant vitamin C, the polyphenol
      content, and the hydrophilic antioxidant capacity of tomato juice, baked
      tomatoes, tomato sauce, and tomato soup. During the production of tomato juice
      and during the preparation of the other tomato products, samples were taken after
      different times, respectively, after each particular production step. High
      performance liquid chromatography was used to determine the content of vitamin C.
      The total phenolics content was analyzed spectrophotometrically by using the
      Folin-Ciocalteu method. The hydrophilic antioxidant capacity was measured by
      using three different methods: the Trolox equivalent antioxidant capacity assay,
      the ferric reducing antioxidant power test, and the photochemiluminescence assay.
      The vitamin C contents of the tomato products decreased during the thermal
      processing of tomatoes. In contrast, the total phenolics concentration and the
      water soluble antioxidant capacity increased.

PMID- 14690381
TI  - Influence of distillation system, oak wood type, and aging time on composition of
      cider brandy in phenolic and furanic compounds.
AB  - A control of phenolic and furanic compounds in cider brandy was carried out
      during maturation in oak casks, studying three technological factors:
      distillation (rectification column vs double distillation), oak wood type (French
      vs American), and aging time (32 months). Gallic acid and benzoic and cinnamic
      aldehydes significantly increased during maturation of cider brandies, the
      highest level of these phenolics being obtained when aging was conducted in
      French oak casks. Benzoic acids increased during aging, though furanic compounds
      were not influenced by the time factor. Distillation and wood factors
      significantly influenced furanic concentration; 5-hydroxymethylfurfural not was
      detected in fresh spirits and was extracted in the highest proportion in French
      oak. Volatile furanics, such as 5-methylfurfural, furfural, and 2-furylmethyl
      ketone, were influenced by the distillation factor, with the use of the double
      distillation system producing a higher level of these compounds. Scopoletin was
      the majority coumarin detected in cider brandies, the highest yield of which was
      obtained with the use of American oak.

PMID- 14690382
TI  - Effect of mild-heat and high-pressure processing on banana pectin methylesterase:
      a kinetic study.
AB  - Pectin methylesterase (PME) was extracted from bananas and purified by affinity
      chromatography. The thermal-high-pressure inactivation (at moderate temperature,
      30-76 degrees C, in combination with high pressure, 0.1-900 MPa) of PME was
      investigated in a model system at pH 7.0. Under these conditions, the stable
      fraction was not inactivated and isobaric-isothermal inactivation followed a
      fractional-conversion model. At lower pressure (< or =300-400 MPa) and higher
      temperature (> or =64 degrees C), an antagonistic effect of pressure and heat was
      observed. Third-degree polynomial models (derived from the thermodynamic model)
      were successfully used to describe the heat-pressure dependence of the
      inactivation rate constants.

PMID- 14690383
TI  - Volatile compounds and phenolic composition of virgin olive oil: optimization of
      temperature and time of exposure of olive pastes to air contact during the
      mechanical extraction process.
AB  - The operative conditions of malaxation such as temperature and time of exposure
      of olive pastes to air contact (TEOPAC) affect volatile and phenolic composition
      of virgin olive oil (VOO) and, as a consequence, its sensory and healthy
      qualities. In this paper, optimal temperature and TEOPAC during malaxation were
      studied, in lab scale, in two Italian cultivars using phenolic compounds,
      volatile composition, and sensory analysis of VOO as markers. The optimal
      temperature and TEOPAC, selected by response surface modeling,were cultivar
      dependent being 30 min of TEOPAC at the lowest temperature investigated (22
      degrees C) and 0 min of TEOPAC at 26 degrees C for Frantoio and Moraiolo
      cultivars, respectively.

PMID- 14690384
TI  - Anthocyanin transformation in Cabernet Sauvignon wine during aging.
AB  - Anthocyanins in Cabernet Sauvignon grapes and wines were elucidated by HPLC
      MS/MS. Major anthocyanins in Cabernet Sauvignon grape extract are malvidin 3-O
      glucoside and malvidin 3-O-acetylglucoside. In matured wine, anthocyanins are
      transformed to anthocyanin-vinyl derivatives, ethyl bridged anthocyanin-flavanol
      adducts, and anthocyanin-flavanol adducts. The major anthocyanin pigments are
      malvidin 3-O-glucoside-pyruvate, malvidin 3-O-acetylglucoside-pyruvate, malvidin
      3-O-coumaroylglucoside-pyruvate, malvidin 3-O-glucoside-4-vinylphenol, malvidin 3
      O-acetylglucoside-4-vinylphenol, and malvidin 3-O-coumaroylglucoside-4
      vinylphenol. The presence of syringetin 3-O-glucoside and syringetin 3-O
      acetylglucoside has been established for the first time in grape and wine.

PMID- 14690385
TI  - Variation in surface chemical constituents of cotton (Gossypium hirsutum) fiber
      as a function of maturity.
AB  - Modern cotton yarn production technology has made it imperative that new
      predictors of yarn spinning efficiency be determined. Surface frictional forces
      play a large role in spinning efficiency, yet little is known about the chemical
      constituents comprising the cotton fiber surface or their respective roles in
      inter-fiber frictional behavior. Major cotton fiber surface chemical components
      including pectin, wax, soluble salts, and sugars were quantified, and their
      respective relationships to cotton fiber maturity, as measured by micronaire,
      determined for 87 cotton samples exhibiting large variations in age, micronaire,
      genetics, and growing region. In the case of pectin and wax, inverse
      relationships with micronaire were found, whereas salts and sugars exhibit linear
      relationships with micronaire. Using these mathematical relationships, it will be
      possible to develop predictive models of whether spinning performance of
      different cottons is affected by deviations of the chemical constituents from the
      determined relationships.

PMID- 14690386
TI  - Proanthocyanidin composition in the seed coat of lentils (Lens culinaris L.).
AB  - Lentils (Lens culinaris L.) are a popular food in many countries. However, little
      is known about their phenolic composition. Because polyphenols in lentils are
      located essentially in their seed coat, the objective of this work was to study
      the composition of proanthocyanidins, the major group of polyphenols, in this
      part of the tissue. The use of C(18) Sep-Pak cartridges permitted the
      fractionation of lentil seed coat extract into monomer, oligomer, and polymer
      proanthocyanidin fractions. Subsequent thiolysis of oligomer and polymer
      fractions followed by HPLC analysis allowed the mean degree of polymerization
      (mDP) and the structural composition of proanthocyanidins to be determined. A
      fractionation of lentil seed coat extracts on a polyamide column followed by HPLC
      and HPLC-DAD-MS analyses was used to identify the individual proanthocyanidins.
      The results showed that the major monomeric flavan-3-ol was (+) catechin-3
      glucose, with lesser amounts of (+)-catechin and (-)-epicatechin. In the oligomer
      fraction, various dimer, trimer, and tetramer proanthocyanidins constituted of
      catechin, gallocatechin, and catechin gallate units were identified, and several
      procyanidins and prodelphinidins from pentamers to nonamers constitute the
      polymer fraction. The most abundant proanthocyanidins in the seed coat of lentils
      are the polymers (65-75%), with a mDP of 7-9, followed by the oligomers (20-30%),
      with a mDP of 4-5.

PMID- 14690387
TI  - Distribution of [(14)C]imidacloprid in sunflowers (Helianthus annuus L.)
      following seed treatment.
AB  - Imidacloprid, a neonicotinic insecticide, has been used as a seed dressing
      (Gaucho) to protect crops against soil and aerial insects. However, French
      beekeepers observed abnormal behavior of bees foraging on sunflowers and
      suspected a link between the imidacloprid seed treatment and the observed bee
      syndrome. This work studies the distribution of [(14)C-imidazolidin]imidacloprid
      (1 mg/seed) in three stages of Gaucho-treated sunflowers grown in an outdoor
      lysimeter. Plants absorbed <10% of [(14)C]imidacloprid spiked on seeds, and 75%
      of that absorbed radioactivity was found in cotyledons. Concentrations in the
      upper leaves were 20 times lower than in the first leaves. From the extracted
      radioactivity, imidacloprid accounted for 50% and metabolites for the other 50%.
      Four major metabolites can be detected, in variable concentrations, among which
      the hydroxy- and olefin-imidacloprid have toxicities equivalent to that of
      imidacloprid. In pollen, concentrations of imidacloprid were 13 ng x g(-1). Thus,
      imidacloprid residues from Gaucho seed treatment contaminated sunflower pollen,
      involving the translocation of imidacloprid within the plant.

PMID- 14690388
TI  - Degradation of isoxaflutole (balance) herbicide by hypochlorite in tap water.
AB  - Chlorine has been widely employed for the disinfection of drinking water.
      Additionally, it has the capacity to oxidize many organic compounds in water.
      Isoxaflutole (Balance; IXF) belongs to a new class of isoxazole herbicides.
      Isoxaflutole has a very short soil half-life and rapidly degrades to a stable and
      phytotoxic metabolite, diketonitrile (DKN). Further degradation of DKN produces a
      nonbiologically active benzoic acid (BA) metabolite. In experiments using high
      performance liquid chromatography-UV spectroscopy (HPLC-UV) and HPLC tandem mass
      spectrometry (HPLC-MS/MS), DKN was found to rapidly react with hypochlorite in
      tap water, yielding the BA metabolite as the major end product. One milligram per
      liter (19 microM) of hypochlorite residue in tap water was able to completely
      oxidize up to 1600 microg/L (4.45 micromol/L) of DKN. In tap water, the
      disappearance of IXF was much more rapid than in DI water. As soon as the IXF is
      hydrolyzed to DKN, the DKN quickly reacts with the OCl(-) to form nonphytotoxic
      BA. As a result, the herbicide solutions prepared with tap water at 500 microg/L
      will no longer possess any herbicidal activity after 48 h of storage. However, in
      agronomic settings, highly concentrated tank solutions (600-800 mg/L) may be
      prepared with tap water since the conversion of IXF to BA would represent <5% of
      the herbicide; therefore, any impact on the herbicide efficacy would be
      negligible. Results of this study show that current chlorination disinfection
      protocols in municipal water systems would completely eliminate the phytotoxic
      form of this new herbicide, DKN, from drinking water supplies; yet, farmers can
      use chlorinated tap water without significant loss of efficacy.

PMID- 14690389
TI  - Biodegradation kinetics of endosulfan by Fusarium ventricosum and a Pandoraea
      species.
AB  - Endosulfan, classified as an organochlorine pesticide, is rated by the U.S. EPA
      as a Category 1 pesticide with extremely high acute toxicity. This study
      describes the biodegradation kinetics of endosulfan and the metabolic pathway
      utilized by Fusarium ventricosum and a Pandoraea sp. Complete disappearance of
      both alpha- and beta-endosulfan was observed during 12 days of incubation with F.
      ventricosum in flasks containing 100 mg L(-)(1) of endosulfan. The rate constants
      (k) for biodegradation of alpha- and beta-endosulfan by F. ventricosum using zero
      order kinetics were 14.22 and 6.60 mg L(-)(1) day(-)(1), respectively. The
      Pandoraea sp. degraded about 95 and 100% of alpha- and beta-endosulfan,
      respectively, in 18 days of incubation in flasks spiked with 100 mg L(-)(1) of
      endosulfan. The rate constants (k) for biodegradation of alpha- and beta
      endosulfan by the Pandoraea sp. were 8.19 and 3.78 mg L(-)(1) day(-)(1),
      respectively. Both fungal and bacterial strains formed less toxic endosulfan diol
      and endosulfan ether as metabolites during metabolism of endosulfan. The results
      of this study suggest that these novel strains may be used for the bioremediation
      of endosulfan-contaminated sites.

PMID- 14690390
TI  - Changes in macroscopic viscosity do not affect the release of aroma aldehydes
      from a pectinaceous food model system of low sucrose content.
AB  - The effects of pectin and viscosity on the release of a systematic series of
      aldehydes (alkanals, methyl-alkanals, alkenals, and alkandienals) were studied in
      a food model system of low sucrose content (10% w/w). The viscosity was varied by
      adding different amounts of Ca(2+) (0, 13.5, and 27 mg/g pectin) to the model
      system of constant pectin concentration (0.4% w/w). Air-liquid partition
      coefficients, K (37 degrees C), of the aroma compounds were determined in aqueous
      and pectin-thickened solutions. Diffusivities of the aroma compounds in water and
      three pectin-thickened solutions were estimated from release rate constants that
      were obtained via timed collection of volatiles in the gas phase and
      quantifications by dynamic headspace-gas chromatography. The partition
      coefficients increased as the carbon chain increased within each homologous
      series. Overall, no significant difference was found between partition
      coefficients of aldehydes in water and in pectin solutions except for 2-methyl
      propanal and butanal that showed higher K values when pectin was present.
      Furthermore, the diffusional properties of the model system with a constant
      pectin level (0.4% w/w) remained constant when the viscosity was increased from
      0.001 to 150 Pa s. It was concluded that neither pectin nor alterations in
      macroscopic viscosity as such influenced the release of aldehydes from the pectin
      thickened food model system.

PMID- 14690391
TI  - On-line gas chromatography combustion/pyrolysis isotope ratio mass spectrometry
      (HRGC-C/P-IRMS) of pineapple (Ananas comosus L. Merr.) volatiles.
AB  - By use of extracts prepared by liquid-liquid separation of the volatiles from
      self-prepared juices of pineapple fruits (Ananas comosus) (n = 14) as well as
      commercial pineapple recovery aromas/water phases (n = 3), on-line capillary gas
      chromatography-isotope ratio mass spectrometry was employed in the combustion (C)
      and the pyrolysis (P) modes (HRGC-C/P-IRMS) to determine the delta(13)C(VPDB) and
      delta(2)H(VSMOW) values of selected pineapple flavor constituents. In addition to
      methyl 2-methylbutanoate 1, ethyl 2-methylbutanoate 2, methyl hexanoate 3, ethyl
      hexanoate 4, and 2,5-dimethyl-4-methoxy-3[2H]-furanone 5, each originating from
      the fruit, the delta(13)C(VPDB) and delta(2)H(VSMOW) data of commercial synthetic
      1-5 and "natural" (biotechnologically derived) 1-4 were determined. With
      delta(13)C(VPDB) data of pineapple volatiles 1-4 varying from -12.8 to -24.4 per
      thousand, the range expected for CAM metabolism was observed. Compound 5 showed
      higher depletion from -20.9 to -28.6 per thousand. A similar situation was given
      for the delta(2)H(VSMOW) values of 3-5 from pineapple ranging from -118 to -191
      per thousand, whereas 1 and 2 showed higher depleted values from -184 to -263 per
      thousand. In nearly all cases, analytical differentiation of 1-5 from pineapple
      and natural as well as synthetic origin was possible. In general, natural and
      synthetic 1-5 exhibited delta(13)C(VPDB) data ranging from -11.8 to -32.2 per
      thousand and -22.7 to -35.9 per thousand, respectively. Their delta(2)H(VSMOW)
      data were in the range from -242 to -323 per thousand and -49 to -163 per
      thousand, respectively.

PMID- 14690392
TI  - Effect of pH on the thermal stability of potent roasty odorants, 3-mercapto-3
      methylbutyl esters, in coffee drink.
AB  - The effect of pH on the thermal stability of potent roasty odorants, 3-mercapto-3
      methylbutyl esters, in coffee drinks was investigated. The concentration of 3
      mercapto-3-methylbutyl formate in the coffee drink was drastically decreased
      during the heat processing. However, the residual ratio of this compound in the
      coffee drink adjusted to pH 5.0 was higher than that of pH 6.5. On the other
      hand, the residual ratios of 3-mercapto-3-methylbutyl acetate showed high values
      in the coffee drinks adjusted to both pHs. In the pH range of 3-7, the residual
      ratios of 3-mercapto-3-methylbutyl formate in aqueous model solutions varied
      depending on the pH value. It had a thermal stability maximum at pH 4.0, while 3
      mercapto-3-methylbutyl acetate showed stability during heat processing over all
      the pH values tested. In addition, the residual ratios of the formate and acetate
      esters, which were composed of various alcohol derivatives, showed the same
      tendency as that of the 3-mercapto-3-methylbutyl esters. These results suggested
      that the low thermal stability and pH dependence of 3-mercapto-3-methylbutyl
      formate are based on the structure of the formate ester.

PMID- 14690393
TI  - Characterization of odor-active compounds in Californian chardonnay wines using
      GC-olfactometry and GC-mass spectrometry.
AB  - Nineteen commercial Californian Chardonnay wines were analyzed by gas
      chromatography-mass spectrometry (GC-MS). Freon extracts of wines were separated
      by silica gel chromatography into three fractions. Volatiles were quantified by
      GC analysis of each fraction using internal standards added to the wine prior to
      Freon extraction. Twelve of the 19 wines were evaluated by GC-Olfactometry (GC
      O). Of the 81 compounds shown to be odor-active (OA) by GC/O, 74 were quantified
      and 61 were tentatively identified, all of which had been previously reported in
      grapes or wines. Overall concentrations of compounds with floral or oak-related
      aromas were higher in wines shown by descriptive analysis to be high in intensity
      of either floral or oak notes, respectively. The relationship between sensory
      intensity ratings from a previous descriptive analysis of the wines and 74 OA
      compounds was modeled by partial least-squares regression (PLS) analysis. This
      PLS model only explained 17% of the variation in the OA variables, whereas a PLS
      using a subset of 16 OA peaks explained 64 and 47% of variance in the sensory and
      GC data, respectively. Fruity wines high in peach, citrus, and floral terms were
      separated from those high in oak-related sensory attributes (oak, vanilla,
      caramel, spice, and butter). In both PLS models, the fruity and floral terms were
      associated with isoamyl acetate, 2-phenylethyl acetate, linalool and two unknowns
      exhibiting minty and bandaid-caramel odors; the oaky attributes were associated
      with vanillin, oak-lactones, 4-ethyl guaiacol, gamma-nonalactone, 2-acetyl furan,
      eugenol, 2-methoxy phenol, and two unknowns with plastic and smoky odors.

PMID- 14690394
TI  - Reaction of lentil trypsin-chymotrypsin inhibitors with human and bovine
      proteinases.
AB  - Four trypsin-chymotrypsin inhibitors from Syrian local small lentils were
      selected to study the reasons for their different action against human and bovine
      proteinases. Chemical modification experiments, enzymatic modifications followed
      by carboxypeptidase degradation, and characterization of the inhibitor/enzyme
      complexes formed were performed. All four Lens culinaris inhibitors (LCI)
      contained arginine at the trypsin-reactive site, and tyrosine (LCI-1.7 and LCI
      2.2), phenylalanine (LCI-3.3), or leucine (LCI-4.6) at the chymotrypsin-reactive
      site. The inhibition of more than one molecule of human chymotrypsin per molecule
      of inhibitor was caused by the additional and atypical binding at the trypsin
      reactive site of all four inhibitors. The approximately 2.5-fold higher
      inhibition of human chymotrypsin compared to bovine chymotrypsin was the result
      of two effects, the additional binding of human chymotrypsin at the trypsin
      reactive site and the low inhibition of bovine chymotrypsin. As a consequence,
      human enzyme preparations or suitable conversion factors should be used to
      evaluate the effect of such inhibitors in foods.

PMID- 14690395
TI  - Composition and cellular localization of tannins in grape seeds during
      maturation.
AB  - Cell walls were isolated from seeds of grape berries (Vitis vinifera L.), and
      proanthocyanidin composition was determined over the course of ripening for
      different levels of vine water status. During the ripening period the tannins
      from the cell walls were always more polymerized than those from the inner part
      of the cell. At maturity this difference becomes more significant compared to
      veraison, due to a significant increase in the mean degree of polymerization of
      the cell wall tannins. The tannin composition was typical of grape seed tannins
      and was quite similar in the two cell fractions studied, but the epicatechin
      gallate proportion was significantly higher in the cell wall fraction. There were
      no significant effects of water deficit on composition and polymerization of seed
      tannins.

PMID- 14690396
TI  - Principal component and linear discriminant analyses of free amino acids and
      biogenic amines in hungarian wines.
AB  - Principal component analysis (PCA) and linear discriminant analysis (LDA) were
      used to classify 187 Hungarian white and red wines according to wine-making
      technology, geographic origin (wine-making region), grape variety, and year of
      vintage based on free amino acid and biogenic amine contents. Determination of
      free amino acids and biogenic amines was accomplished by ion-exchange
      chromatography. Six principal components accounted for >77% of the total variance
      in the data. The plots of component loadings showed significant groupings of free
      amino acids and biogenic amines. The component scores grouped according to wines
      made by different wine-making technologies. Using LDA the variables with a major
      discriminant capacity were determined. Almost complete classification (94.7%) was
      achieved concerning both white and red wines and wines made by different wine
      making technologies. The results of differentiation between white wines according
      to geographic origin, grape variety, and year of vintage were 70.8, 62.4, and
      73.5%, respectively. The same numbers for red wines according to geographic
      origin, grape variety, and year of vintage were 64.9, 71.6, and 82.4%,
      respectively.

PMID- 14690397
TI  - Antioxidant constituents of radish sprout (Kaiware-daikon), Raphanus sativus L.
AB  - Methanol extracts of 11 kinds of commonly available vegetables were examined for
      hydroxyl radical scavenging potency using the bleomycin-Fe method. In this
      method, the iron ion and bleomycin in water form hydroxyl radicals, and the
      scavenging activity is monitored by the modified thiobarbituric acid method. All
      extracts showed scavenging capacity, even though the activity of some of them was
      lower than that of l-ascorbic acid. Those vegetables were classified into three
      groups according to their activity, groups showing strong activity, moderate
      activity, and weak activity, as compared to the activity of l-ascorbic acid at
      the same concentration. Among them, the methanol extract of radish sprout
      (Japanese name "kaiware-daikon") exhibited the highest potency (1.8 times as l
      ascorbic acid). Then, we investigated the constituents of the methanol extract of
      radish sprout and the contribution to the overall activity of each compound by
      examining their activity. As the result, several kinds of sinapinic acid esters
      and flavonoids were isolated with high radical scavenging potency, which must
      contribute substantially to the activity.

PMID- 14690398
TI  - Superoxide radical scavenging activity of the major polyphenols in fresh plums.
AB  - The effect of polyphenols among different varieties of plums on superoxide
      radical scavenging activity (SRSA) was studied by an enzymatic method and their
      IC(50) values were determined. We found that the SRSA levels of the polyphenols
      were closely related to their chemical structures; cyanidin showed the lowest
      IC(50) among the polyphenols examined, and aglycones are more effective than
      their glycosides. BY 69-339 cultivar exhibited the lowest IC(50) among the eleven
      plum cultivars, which means the highest antioxidant activity in scavenging
      superoxide radicals, followed by French Damson, Cacaks Best, Beltsville Elite
      B70197, Empress, Castleton, Stanley, NY 6, NY 101, Mirabellier, and NY 9. IC(50)
      values showed a higher correlation with total flavonoids (r (2) = 0.8699) than
      total phenolics (r (2) = 0.8355), which indicated that flavonoids might
      contribute to the total SRSA more directly than other polyphenols. Anthocyanins
      in plums appeared to be the major contributors to the total SRSA, except for two
      yellow cultivars having no anthocyanins. Chlorogenic acid was the predominant
      phenolic acid, and it also exhibited SRSA significantly in the range of 1.0 to
      94.9%. Quercetins were the major flavonols in plums. However, they showed
      relatively low contribution to the total SRSA.

PMID- 14690399
TI  - Size, stability, and entrapment efficiency of phospholipid nanocapsules
      containing polypeptide antimicrobials.
AB  - The effect of lipid composition [phosphatidylcholine (PC), phosphatidylglycerol
      (PG), and cholesterol] on size, stability, and entrapment efficiency of
      polypeptide antimicrobials in liposomal nanocapsules was investigated. PC,
      PC/cholesterol (70:30), and PC/PG/cholesterol (50:20:30) liposomes had entrapment
      efficiencies with calcein of 71, 57, and 54% with particle sizes of 85, 133, and
      145 nm, respectively. Co-encapsulation of calcein and nisin resulted in
      entrapment efficiencies of 63, 54, and 59% with particle sizes of 144, 223, and
      167 nm for PC, PC/cholesterol (70:30), and PC/PG/cholesterol (50:20:30),
      respectively. Co-encapsulation of calcein and lysozyme yielded entrapment
      efficiencies of 61, 60, and 61% with particle sizes of 161, 162, and 174 nm,
      respectively. The highest concentration of antimicrobials was encapsulated in
      100% PC liposomes. Nisin induced more calcein release compared to lysozyme.
      Results demonstrate that production and optimization of stable nanoparticulate
      aqueous dispersions of polypeptide antimicrobials for microbiological
      stabilization of food products depend on selection of suitable lipid
      antimicrobial combinations.

PMID- 14690400
TI  - Variation in cell wall composition among forage maize (Zea mays L.) inbred lines
      and its impact on digestibility: analysis of neutral detergent fiber composition
      by pyrolysis-gas chromatography-mass spectrometry.
AB  - Cell wall digestibility is an important determinant of forage quality, but the
      relationship between cell wall composition and digestibility is poorly
      understood. We analyzed the neutral detergent fiber (NDF) fraction of nine maize
      inbred lines and one brown midrib3 mutant with pyrolysis-gas chromatography-mass
      spectrometry (Py-GC-MS). Among 29 pyrolysis fragments that were quantified, two
      carbohydrate-derived and six lignin-derived fragments showed statistically
      significant genetic variation. The pyrolysis products 4-vinyl phenol and 2,6
      dimethoxy-4-vinyl phenol were negatively correlated with digestibility, whereas
      furfural and 3-(4-hydroxyphenyl)-3-oxopropanal showed a positive correlation with
      digestibility. Linear discriminant analysis of the pyrolysis data resulted in the
      resolution of groups of inbred lines with different digestibility properties
      based on their chemical composition. These analyses reveal that digestibility is
      governed by complex interactions between different cell wall compounds, but that
      several pyrolysis fragments can be used as markers to distinguish between maize
      lines with different digestibility.

PMID- 14690401
TI  - Biochemical properties of black drum and sheepshead seabream skin collagen.
AB  - Acid-soluble collagen (ASC) and pepsin solubilized collagen (PSC) were isolated
      from the skins of black drum (Pogonias cromis) and sheepshead seabream
      (Archosargus probatocephalus) harvested in the Gulf of Mexico coastal waters. The
      yields of ASCs on dry basis from black drum and sheepshead were estimated at 2.3
      and 2.6%, and the yields of PSCs were 15.8 and 29.3%, respectively. Analyses of
      molecular weight profile, amino acid composition, and secondary structure showed
      that the skin collagens from both species were typical type-I collagen. The
      molecular mass of alpha(1) and alpha(2) subunits, as determined by SDS-PAGE using
      Tris-Acetate gels, was 127 kDa and 116 kDa, respectively. The amino acid
      composition of ASC and PSC for both species was closer to calf skin ASC than to
      cod skin ASC. Thermal denaturation temperatures, measured by melting point using
      circular dichroism, gave the following values: black drum ASC, 34.2 degrees C;
      sheepshead ASC, 34.0 degrees C; black drum PSC, 35.8 degrees C; sheepshead PSC,
      34.3 degrees C. The literature value for the heat stability of calf skin collagen
      is 36.3 degrees C. The potentials of collagens from black drum and sheepshead
      skins in the functional food, healthcare, and pharmaceutical industries are
      discussed.

PMID- 14690402
TI  - Pressure/temperature combined treatments of precursors yield hormone-like
      peptides with pyroglutamate at the N terminus.
AB  - Peptides containing the cyclic product of glutamine at the N terminus are usually
      biologically active. If the cyclization of glutamine was associated with a volume
      reduction, pressure should displace the equilibrium in the direction of the lower
      volume. Here, results in model solutions and in whey are discussed, showing that
      the theorized cyclization of glutamine in Gln-His-ProNH(2) or Gln-Leu-ProNH(2) is
      significantly accelerated during the application of heat and even more strongly
      when elevated temperature and pressure combinations are used. The reaction rate
      depended on the intensity of the pressure treatment, the pH, and the nature of
      the amino acids adjacent to glutamine. The products of the reaction were
      identified as thyrotropin-releasing hormone (TRH) and [Leu(2)]TRH. The reported
      reactions could affect the naturally balanced concentration of short-chain
      peptides in foods and therefore induce unpredictable biological effects.

PMID- 14690403
TI  - Steric effects governing disulfide bond interchange during thermal aggregation in
      solutions of beta-lactoglobulin B and alpha-lactalbumin.
AB  - Intermolecular disulfide bond formation in pure beta-lactoglobulin (beta-Lg) B
      and in its 1:1 mixture with alpha-lactalbumin (alpha-La), heated at 85 degrees C
      for 10 min in solutions of low and high (100 mM NaCl) ionic strength and pH 6.0,
      was studied by reverse-phase HPLC and MALDI-TOF mass spectrometry. Disulfide
      bonding between beta-Lg monomers was more extensive than reported in the
      literature for a temperature of 68.5 degrees C, including formation of trimers
      connected by two of the three adjacent cysteines, C106/C119/C121. The
      participation of the different thiol groups in disulfide bonds appeared to depend
      on their location in the native structure, with surface-located cysteines more
      involved than internally located ones. This also applied to alpha-La-beta-Lg
      interactions, where the predominant participants were the surface-located
      alphaC111, alphaC120, alphaC61, and alphaC6. The least active participant was
      alphaC28, suggesting that it becomes sterically inaccessible during unfolding of
      the protein. High ionic strength apparently promoted disulfide bonding. The order
      of cysteine participation at the high ionic strength was similar to that at low
      ionic strength, with fewer native-location bonds observed and a lower activity of
      some groups, such as beta-C106/C119/C121 and alphaC61.

PMID- 14690404
TI  - Combined influence of NaCl and sucrose on heat-induced gelation of bovine serum
      albumin.
AB  - The combined influence of a strongly interacting cosolvent (NaCl) and a weakly
      interacting cosolvent (sucrose) on the heat-induced gelation of bovine serum
      albumin (BSA) was studied. The dynamic shear rheology of 4 wt % BSA solutions
      containing 0 or 20 wt % sucrose and 0-200 mM NaCl was monitored as they were
      heated from 30 to 90 degrees C at 1.5 degrees C min(-)(1), held at 90 degrees C
      for 120 min, and then cooled back to 30 degrees C at -1.5 degrees C min(-)(1).
      The turbidity of the same solutions was monitored as they were heated from 30 to
      95 degrees C at 1.5 degrees C min(-)(1) or held isothermally at 90 degrees C for
      10 min. NaCl had a similar effect on BSA solutions that contained 0 or 20 wt %
      sucrose, with the gelation temperature decreasing and the final gel strength
      increasing with increasing salt concentration and the greatest changes occurring
      between 25 and 100 mM NaCl. Nevertheless, the presence of sucrose did lead to an
      increase in the gelation temperature and final gel strength and a decrease in the
      final gel turbidity. The impact of NaCl on gel characteristics was attributed
      primarily to its ability to screen electrostatic interactions between charged
      protein surfaces, whereas the impact of sucrose was attributed mainly to its
      ability to increase protein thermal stability and strengthen the attractive
      forces between proteins through a preferential interaction mechanism.

PMID- 14690405
TI  - Modulation of hepatic drug metabolizing enzymes and oxidative status by rooibos
      (Aspalathus linearis) and Honeybush (Cyclopia intermedia), green and black
      (Camellia sinensis) teas in rats.
AB  - Rooibos and honeybush teas significantly (P < 0.05) enhanced the activity of
      cytosolic glutathione S-transferase alpha. A significant (P < 0.05) to marginal
      (P < 0.1) increase in the activity of the microsomal UDP-glucuronosyl transferase
      was obtained with unprocessed rooibos and honeybush teas, respectively. Oxidized
      glutathione (GSSG) levels were significantly (P < 0.05) reduced in the liver of
      all tea treated rats while reduced glutathione (GSH) was markedly increased in
      the liver of the herbal tea treated rats. These changes resulted in a significant
      (P < 0.05) increase in the GSH/GSSG ratio by the unprocessed, processed rooibos
      and unprocessed honeybush teas. Green and black teas markedly to significantly
      decreased the oxygen radical absorbance capacity in liver homogenates,
      respectively. Modulation of phase II drug metabolizing enzymes and oxidative
      status in the liver may be important events in the protection against adverse
      effects related to mutagenesis and oxidative damage.

PMID- 14690406
TI  - Volatile organic compounds in foods: a five year study.
AB  - A purge and trap procedure was used with gas chromatography-mass spectrometry
      determination to analyze 70 foods for volatile organic compounds (VOCs). The
      results from analyses over a 5 year period (1996-2000) are reported. VOCs were
      found in at least one sample of all foods tested, although no single compound was
      found in each of the foods. The total amount of VOCs found in a single food item
      over the 5 year period ranged from 24 to 5328 ppb, with creamed corn (canned) the
      lowest and cheddar cheese the highest. Benzene was found in all foods except
      American cheese and vanilla ice cream. Benzene levels ranged from 1 to 190 ppb,
      with the highest level found in fully cooked ground beef. Benzene was found in 12
      samples of cooked ground beef, with an average of 40 ppb. Benzene levels above
      100 ppb were also seen in at least one sample each of a cola (138 ppb), raw
      bananas (132 ppb), and cole slaw (102 ppb). This compares to a maximum
      contaminant level of 5 ppb set by the U.S. EPA for drinking water.

PMID- 14690407
TI  - Evaluation of conventional and organic italian foodstuffs for deoxynivalenol and
      fumonisins B(1) and B(2).
AB  - Two lots of human foodstuffs from conventional and organic brand foods were
      purchased from supermarkets and analyzed for three Fusarium toxins,
      deoxynivalenol, by GC-ECD, and fumonisins B(1) and B(2) (FB(1)-FB(2)), by LC-MS.
      The occurrence of deoxynivalenol contamination was higher than 80% in both
      organic and conventional foods; fumonisin B(1) was found in 20% of organic foods
      and in 31% of conventional ones and fumonisin B(2) in more than the 32% of the
      food samples from both the agricultural practices. The highest median
      concentration of deoxynivalenol occurred in conventional rice-based foodstuffs
      (207 microg/kg): that of fumonisin B(1) in conventional maize-based foods (345
      microg/kg) and that of fumonisin B(2) in organic wheat-based foods (210
      microg/kg).

PMID- 14690408
TI  - Assessment of pesticide residues in honey samples from portugal and Spain.
AB  - Fifty samples of honey collected from local markets of Portugal and Spain during
      year 2002 were analyzed for 42 organochlorine, carbamate, and organophosphorus
      pesticide residues. An analytical procedure based on solid-phase extraction with
      octadecyl sorbent followed by gas chromatography-mass spectrometry (GC-MS), for
      organochlorines, and by liquid chromatography-atmospheric pressure chemical
      ionization-mass spectrometry (LC-APCI-MS), for organophosphorus and carbamates,
      has been developed. Recoveries of spiked samples ranged from 73 to 98%, except
      for dimethoate (40%), with relative standard deviations from 3 to16% in terms of
      repeatability, and from 6 to 19% in terms of reproducibility. Limits of
      quantification were from 0.003 to 0.1 mg kg(-)(1). Most of the pesticides found
      in honey were organochlorines. Among them, gamma-HCH was the most frequently
      detected in 50% of the samples, followed by HCB in 32% of the samples and the
      other isomers of HCH (alpha-HCH and beta-HCH) in 28 and 26% of the samples,
      respectively. Residues of DDT and their metabolites were detected in 20% of the
      samples. Of the studied carbamates, both methiocarb and carbofuran were detected
      in 10% of the samples, pirimicarb in 4% and carbaryl in 2%. The only
      organophosphorus pesticides found were heptenophos in 16%, methidathion in 4%,
      and parathion methyl in 2% of honey samples. Results indicate that Portuguese
      honeys were more contaminated than Spanish ones. However, honey consumers of both
      countries should not be concerned about the amounts of pesticide residues found
      in honeys available on the market.

PMID- 14690409
TI  - Modeling tau polymerization in vitro: a review and synthesis.
AB  - The major antigenic component of neurofibrillary pathology in a large number of
      neurodegenerative diseases consists of the microtubule-associated protein tau. It
      is currently unclear how tau protein makes the transition from an important
      component of the microtubule-based cytoskeleton to an insoluble polymerized
      state. In vitro techniques have been employed to study the polymerization of tau
      in an effort to understand the underlying molecular mechanisms responsible for
      this process. These efforts have resulted in the elucidation of roles played by
      the different parts of the molecule in the polymerization process. Here we
      discuss the advantages and disadvantages of the various techniques used to model
      tau polymerization and the discoveries arising from these techniques that have
      led to a better structural understanding of tau polymerization in relation to
      Alzheimer's disease and other tauopathies.

PMID- 14690410
TI  - Peptide ketobenzoxazole inhibitors bound to cathepsin K.
AB  - Potent inhibitors of human cysteine proteases of the papain family have been made
      and assayed versus a number of relevant family members. We describe the synthesis
      of peptide alpha-ketoheterocyclic inhibitors that occupy binding subsites S1'-S3
      of the cysteine protease substrate recognition cleft and that form a reversible
      covalent bond with the Cys 25 nucleophile. X-ray crystal structures of cathepsin
      K both unbound and complexed with inhibitors provide detailed information on
      protease/inhibitor interactions and suggestions for the design of tight-binding,
      selective molecules.

PMID- 14690411
TI  - Secondary mutations M36I and A71V in the human immunodeficiency virus type 1
      protease can provide an advantage for the emergence of the primary mutation D30N.
AB  - Development of resistance mutations in enzymatic targets of human
      immunodeficiency virus 1 (HIV-1) hampers the ability to provide adequate therapy.
      Of special interest is the effect mutations outside the active site of HIV-1
      protease have on inhibitor binding and virus viability. We engineered protease
      mutants containing the active site mutation D30N alone and with the nonactive
      site polymorphisms M36I and/or A71V. We determined the K(i) values for the
      inhibitors nelfinavir, ritonavir, indinavir, KNI272, and AG1776 as well as the
      catalytic efficiency of the mutants. Single and double mutation combinations
      exhibited a decrease in catalytic efficiency, while the triple mutant displayed
      catalytic efficiency greater than that of the wild type. Variants containing M36I
      or A71V alone did not display a significant change in binding affinities to the
      inhibitors tested. The variant containing mutation D30N displayed a 2-6-fold
      increase in K(i) for all inhibitors tested, with nelfinavir showing the greatest
      increase. The double mutants containing a combination of mutations D30N, M36I,
      and A71V displayed -0.5-fold to +6-fold changes in the K(i) of all inhibitors
      tested, with ritonavir and nelfinavir most affected. Only the triple mutant
      showed a significant increase (>10-fold) in K(i) for inhibitor nelfinavir,
      ritonavir, or AG-1776 displaying 22-, 19-, or 15-fold increases, respectively.
      Our study shows that the M36I and A71V mutations provide a greater level of
      inhibitor cross-resistance combined with active site mutation D30N. M36I and
      A71V, when present as natural polymorphisms, could aid the virus in developing
      active site mutations to escape inhibitor binding while maintaining catalytic
      efficiency.

PMID- 14690412
TI  - DNA damage and mutations induced by arachidonic acid peroxidation.
AB  - Endogenous cellular oxidation of omega6-polyunsaturated fatty acids (PUFAs) has
      long been recognized as a contributing factor in the development of various
      cancers. The accrual of DNA damage as a result of reaction with free radical and
      electrophilic aldehyde products of lipid peroxidation is believed to be involved;
      however, the genotoxic and mutation-inducing potential of specific membrane PUFAs
      remains poorly defined. In the present study we have examined the ability of
      peroxidizing arachidonic acid (AA, 20:4omega6) to induce DNA strand breaks, base
      modifications, and mutations. The time-dependent induction of single-strand
      breaks and oxidative base modifications by AA in genomic DNA was quantified using
      denaturing glyoxal gel electrophoresis. Mutation spectra were determined in XP-G
      fibroblasts and a repair-proficient line corrected for this defect by c-DNA
      complementation (XP-G(+)). Mutation frequencies were elevated from approximately
      5- to 30-fold over the background following reaction of DNA with AA for various
      times. The XPG gene product was found to be involved in the suppression of
      mutations after extended reaction of DNA with AA. Arachidonic acid-induced base
      substitutions were consistent with the presence of both oxidized and aldehyde
      base adducts in DNA. The frequency of multiple-base substitutions induced by AA
      was significantly reduced upon correction for the XPG defect (14% vs 2%, P =
      0.0015). Evidence is also presented which suggests that the induced frequency of
      multiple mutations is lesion dependent. These results are compared to published
      data for mutations stimulated by alpha,beta-unsaturated aldehydes identified as
      products of lipid peroxidation.

PMID- 14690413
TI  - Interaction and stimulation of human FEN-1 nuclease activities by heterogeneous
      nuclear ribonucleoprotein A1 in alpha-segment processing during Okazaki fragment
      maturation.
AB  - High-fidelity DNA replication depends on both accurate incorporation of
      nucleotides in the newly synthesized strand and the maturation of Okazaki
      fragments. In eukaryotic cells, the latter is accomplished by a series of
      coordinated actions of a set of structure-specific nucleases, which, with the
      assistance of accessory proteins, recognize branched RNA/DNA configurations. In
      the current model of Okazaki fragment maturation, displacement of a 27-nucleotide
      or longer flap is envisioned to attract replication protein A (RPA), which
      inhibits flap endonuclease-1 (FEN-1) but stimulates Dna2 nuclease for cleavage.
      Dna2 cleavage generates a short flap of 5-7 nucleotides, which resists binding by
      RPA and further cleavage by Dna2. FEN-1 then removes the remaining flap to
      produce a suitable substrate for ligation. However, FEN-1 is not efficient in
      cleaving the short flap, and we therefore set out to identify cellular factors
      that might regulate FEN-1 activity. Through co-immunoprecipitation experiments,
      we have isolated heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), which
      forms a direct complex with FEN-1 and stimulates its enzymatic activities. The
      stimulation by hnRNP A1 is most dramatic using DNA substrates with short flaps.
      With longer flap substrates the hnRNP A1 effect is more modest and is suppressed
      by the addition of RPA. A model is provided to explain the possible in vivo role
      of this interaction and activity in Okazaki fragment maturation.

PMID- 14690414
TI  - Biophysical analyses of the transthyretin variants, Tyr114His and Tyr116Ser,
      associated with familial amyloidotic polyneuropathy.
AB  - The familial amyloidotic polyneuropathy is strictly associated with point
      mutations in the coding region of the transthyretin gene. Here, we focused on the
      mutations in the monomer-monomer and dimer-dimer interaction site of the
      transthyretin tetramer. The naturally occurring amyloidogenic Tyr114His (Y114H)
      and Tyr116Ser (Y116S) variants formed more amyloid fibrils than the wild-type
      transthyretin, nonamyloidogenic Tyr116Val (Y116V) variant, and other
      amyloidogenic variants in previous studies. The secondary, tertiary, and
      quaternary structural stabilities of the Y114H and Y116S variants were compared
      with those of the wild-type transthyretin and nonamyloidogenic Y116V variant. The
      unfolding data indicated that the amyloidogenic Y114H and Y116S mutations reduced
      the stability of the secondary, tertiary, and quaternary structure. Our results
      also indicated that the unfolding of Y114H and Y116S is less cooperative than
      that of the wild-type transthyretin. Moreover, the tetramer of the amyloidogenic
      variants dissociated to the monomer even at pH 7.0, indicating the importance of
      Tyr114 and Tyr116 in strengthening the contacts between monomers and/or dimers of
      the transthyretin molecule.

PMID- 14690415
TI  - Role of helices and loops in the ability of apolipophorin-III to interact with
      native lipoproteins and form discoidal lipoprotein complexes.
AB  - The structure of Locusta migratoria apolipophorin-III consists of a five-helix
      bundle connected by four short loops. The role of the conformational flexibility
      of helices and loops on the lipid-binding activity of this apolipoprotein was
      investigated by disulfide mediated tethering experiments. One disulfide mutant
      tethering the second and fourth loops (L2-L4), and two disulfide mutants
      restricting the flexibility of the neighboring alpha-helices 3 and 4 (H3-H4) and
      1 and 5 (H1-H5), were studied. The ability of the disulfide mutants to interact
      with phospholipid vesicles, mixed micelles of phosphatidylcholine and cholate,
      and in vivo with native spherical lipoprotein particles was studied. The L2-L4
      mutant was active with native lipoproteins as well as being able to form
      discoidal lipoproteins upon incubation with either liposomes or discoidal
      micelles. The H3-H4 mutant was not able to interact with liposomes or native
      lipoproteins but interacted with discoidal micelles. The H1-H5 mutant was unable
      to interact with lipid in any of the three systems. Three conclusions were
      reached: (1) opening of the helix bundle does not require the separation of loops
      2 and 4 as recently proposed by others and (2) alpha-helices 3 and/or 4 are
      involved in the insertion of apoLp-III in both phospholipid bilayers and
      monolayers. The conformational flexibility of helices 3 and 4 is required for the
      lipid-binding activity of apoLp-III. (3) Interaction of helices 1 and/or 5 with
      the lipid surface is required to the formation of stable lipoprotein complexes of
      any kind.

PMID- 14690416
TI  - Direct interaction between substrates and endogenous steroids in the active site
      may change the activity of cytochrome P450 3A4.
AB  - CYP3A4 exhibits unusual kinetic characteristics that result from the metabolism
      of multiple substrate including endogenous steroids and some drugs that coexist
      at the active site. To clarify the mechanism of the effect of endogenous steroids
      on the drug metabolism, the interaction between substrates, nevirapine (NVP) and
      carbamazepine (CBZ), and endogenous steroids was investigated by theoretical
      calculations. When the activities of NVP 2-hydroxylation and CBZ 10,11
      epoxidation by expressed CYP3A4 were measured in the presence of steroids, NVP 2
      hydroxylation was found to be remarkably increased by aldosterone and inhibited
      by estradiol. CBZ 10,11-epoxidation was increased by androstenedione. Three
      dimensional computer modeling has shown that the active site of CYP3A4 is
      especially large, permitting access of two substrate molecules. The interactions
      between NVP and aldosterone and between CBZ and androstenedione were estimated by
      theoretical calculations assuming the substrate and steroids to be present in the
      active site at the same time. It was shown that NVP or CBZ would be stably fixed
      close to the oxygen atom at the sixth ligand of heme by interaction with
      steroids, suggesting that NVP and CBZ may be hydroxylated more easily due to the
      interaction with steroids. Estradiol was also expected to interact with NVP via a
      pi/pi interaction between a benzene ring, in which the NVP hydroxylation site is
      located, and a benzene ring of estradiol, suggested to inhibit the reaction. From
      these results, interactions between the substrate and endogenous steroids in the
      active site may change the activity of CYP3A4.

PMID- 14690417
TI  - Relative influence of hydrophobicity and net charge in the aggregation of two
      homologous proteins.
AB  - A potentially amyloidogenic protein has to be at least partially unfolded to form
      amyloid aggregates. However, aggregation of the partially or totally unfolded
      state of a protein is modulated by at least three other factors: hydrophobicity,
      propensity to form secondary structure, and net charge of the polypeptide chain.
      We propose to evaluate the relative importance of net charge, as opposed to the
      other factors, on protein aggregation and amyloidogenicity. For this aim, we have
      used two homologous proteins that were previously shown to be able to form
      amyloid fibrils in vitro, the N-terminal domain of HypF from Escherichia coli
      (HypF-N) and human muscle acylphosphatase (AcP). The aggregation process from an
      ensemble of partially unfolded conformations is ca. 1000-fold faster for HypF-N
      than for AcP. This difference can mainly be attributed to a higher hydrophobicity
      and a lower net charge for HypF-N than for AcP. By using protein engineering
      methods, we have decreased the net charge of AcP to a value identical to that of
      wild-type HypF-N and increased the net charge of HypF-N to a value identical to
      that of wild-type AcP. Amino acid substitutions were selected to minimize changes
      in hydrophobicity and secondary structure propensities. We were able to estimate
      that the difference in net charge between the two wild-type proteins contributes
      to 20-25% of the difference in their aggregation rates. An understanding of the
      relative influences of these forces in protein aggregation has implications for
      elucidating the complexity of the aggregation process, for predicting the effect
      of natural mutations, and for accurate protein design.

PMID- 14690418
TI  - Nucleosome positioning in the human c-Fos promoter analyzed by in vivo
      footprinting with psoralen and ionizing radiation.
AB  - We performed detailed footprinting analysis of nucleosome positioning in the c
      FOS promoter of living human fibroblasts. The translational position was
      determined by terminal transferase-dependent PCR with 4,5',8-trimethylpsoralen.
      The rotational position was determined by ligation-mediated PCR with ionizing
      radiation. In the middle of the c-FOS promoter, a nucleosome was positioned not
      only translationally but also rotationally. The comparison of the results of our
      in vivo footprinting with those of a previous report on the in vitro footprinting
      of reconstituted nucleosomes revealed that the major in vivo translational
      position was approximately 70 bp upstream of the in vitro position, whereas the
      rotational position was unchanged. The in vivo translational position appears to
      be strongly influenced by the presence of transcription factors, which may
      function as boundaries, while the rotational position appears to be determined
      predominantly by the DNA sequence. We also investigated the influence of the
      transcriptional activation of the c-FOS gene on the positioning of this
      nucleosome. Although it is well-known that there are rapid changes in general
      nuclease sensitivity and chemical modifications of histone in the c-FOS gene upon
      activation, we could not detect any change in the translational or rotational
      position of this nucleosome. The nucleoprotein complex in the c-FOS promoter
      containing the positioned nucleosome and several transcription factors seems to
      be structurally unaltered upon activation, despite the rapid chemical
      modifications of the nucleosome and some of the transcription factors.

PMID- 14690419
TI  - Limited set of amino acid residues in a class Ia aminoacyl-tRNA synthetase is
      crucial for tRNA binding.
AB  - The aim of this work was to characterize crucial amino acids for the
      aminoacylation of tRNA(Arg) by yeast arginyl-tRNA synthetase. Alanine mutagenesis
      was used to probe all the side chain mediated interactions that occur between
      tRNA(Arg2)(ICG) and ArgRS. The effects of the substitutions were analyzed in vivo
      in an ArgRS-knockout strain and in vitro by measuring the aminoacylation
      efficiencies for two distinct tRNA(Arg) isoacceptors. Nine mutants that generate
      lethal phenotypes were identified, suggesting that only a limited set of side
      chain mediated interactions is essential for tRNA recognition. The majority of
      the lethal mutants was mapped to the anticodon binding domain of ArgRS, a helix
      bundle that is characteristic for class Ia synthetases. The alanine mutations
      induce drastic decreases in the tRNA charging rates, which is correlated with a
      loss in affinity in the catalytic site for ATP. One of those lethal mutations
      corresponds to an Arg residue that is strictly conserved in all class Ia
      synthetases. In the known crystallographic structures of complexes of tRNAs and
      class Ia synthetases, this invariant Arg residue stabilizes the idiosyncratic
      conformation of the anticodon loop. This paper also highlights the crucial role
      of the tRNA and enzyme plasticity upon binding. Divalent ions are also shown to
      contribute to the induced fit process as they may stabilize the local tRNA-enzyme
      interface. Furthermore, one lethal phenotype can be reverted in the presence of
      high Mg(2+) concentrations. In contrast with the bacterial system, in yeast
      arginyl-tRNA synthetase, no lethal mutation has been found in the ArgRS specific
      domain recognizing the Dhu-loop of the tRNA(Arg). Mutations in this domain have
      no effects on tRNA(Arg) aminoacylation, thus confirming that Saccharomyces
      cerevisiae and other fungi belong to a distinct class of ArgRS.

PMID- 14690420
TI  - Induced fit and kinetic mechanism of adenylation catalyzed by Escherichia coli
      threonyl-tRNA synthetase.
AB  - Threonyl-tRNA synthetase (ThrRS) must discriminate among closely related amino
      acids to maintain the fidelity of protein synthesis. Here, a pre-steady state
      kinetic analysis of the ThRS-catalyzed adenylation reaction was carried out by
      monitoring changes in intrinsic tryptophan fluorescence. Stopped flow fluorimetry
      for the forward reaction gave a saturable fluorescence quench whose apparent rate
      increased hyperbolically with ATP concentration, consistent with a two-step
      mechanism in which rapid substrate binding precedes an isomerization step. From
      similar experiments, the equilibrium dissociation constants for dissociation of
      ATP from the E.Thr complex (K(3) = 450 +/- 180 microM) and threonine from the
      E.ATP complex (K'(4) = 135 microM) and the forward rate constant for adenylation
      (k(+5) = 29 +/- 4 s(-1)) were determined. A saturable fluorescence increase
      accompanied the pyrophosphorolysis of the E.Thr - AMP complex, affording the
      dissociation constant for PP(i) (K(6) = 170 +/- 50 microM) and the reverse rate
      constant (k(-5) = 47 +/- 4 s(-1)). The longer side chain of beta-hydroxynorvaline
      increased the apparent dissociation constant (K(4[HNV]) = 6.8 +/- 2.8 mM) with
      only a small reduction in the forward rate (k'(+5[HNV]) = 20 +/- 3.1 s(-1)). In
      contrast, two nonproductive substrates, threoninol and the adenylate analogue 5'
      O-[N-(L-threonyl)sulfamoyl]adenosine (Thr-AMS), exhibited linear increases in
      k(app) with ligand concentration, suggesting that their binding is slow relative
      to isomerization. The proposed mechanism is consistent with steady state kinetic
      parameters. The role of threonine binding loop residue Trp434 in fluorescence
      changes was established by mutagenesis. The combined kinetic and molecular
      genetic analyses presented here support the principle of induced fit in the ThrRS
      catalyzed adenylation reaction, in which substrate binding drives conformational
      changes that orient substrates and active site groups for catalysis.

PMID- 14690421
TI  - Role of the C-terminal extrinsic region of the alpha polypeptide of the light
      harvesting 2 complex of Rhodobacter sphaeroides: a domain swap study.
AB  - The LH1 and LH2 complexes of Rhodobacter sphaeroides form ring structures of 16
      and 9 protomers, respectively, comprising alpha and beta polypeptides,
      bacteriochlorophylls (Bchl), and carotenoids. Using the LH2 complex as a starting
      point, two chimeric LH complexes were constructed incorporating the alphaC
      terminal domain of either the Rb. sphaeroides LH1 complex or the Rhodospirillum
      molischianum LH2 complex. The LH1 domain swap produced a new red-shifted
      component that comprised approximately 30% of the total absorbance. In the
      LH1alpha C-terminal mutant this new red-shifted species acts as the terminal
      emitter, with the new emission maximum located 10 nm further to the red than for
      the WT. Raman spectroscopy indicates that a fraction of the B850 Bchls is
      involved in relatively weak H-bonds, possibly involving the alphaTrp(+11) residue
      within the new alphaC-terminus, consistent with a more LH1-like character for one
      of the Bchls. The CD data indicate that the domain swaps have perturbed the
      native arrangement of the B850 Bchls, including the site energy difference
      between the alpha- and beta-bound Bchls. Thus, the normal energetic structure of
      the ring system has been disrupted, with one component blue shifted due to the
      presumed loss of an H-bond donor and the other red shifted by the influence of
      the new alphaC-terminal domain. The dichotomous response of the mutants to the
      carotenoids incorporated, spheroidenone or neurosporene, strongly suggests that
      the C-terminal region of the alpha polypeptide is involved in binding a
      carotenoid. The projection map of the LH1alpha C-terminal mutant complex was
      determined in negative stain at 25 A resolution, and it shows a diameter of 53 A,
      compared to 50 A for the WT. Hence these new spectral properties have not been
      accompanied by an alteration in ring size.

PMID- 14690422
TI  - Caveolin-1 null (-/-) mice show dramatic reductions in life span.
AB  - Caveolae are 50-100 nm flask-shaped invaginations of the plasma membrane found in
      most cell types. Caveolin-1 is the principal protein component of caveolae
      membranes in nonmuscle cells. The recent development of Cav-1-deficient mice has
      allowed investigators to study the in vivo functional role of caveolae in the
      context of a whole animal model, as these mice lack morphologically detectable
      caveolae membrane domains. Surprisingly, Cav-1 null mice are both viable and
      fertile. However, it remains unknown whether loss of caveolin-1 significantly
      affects the overall life span of these animals. To quantitatively determine
      whether loss of Cav-1 gene expression confers any survival disadvantages with
      increasing age, we generated a large cohort of mice (n = 180), consisting of Cav
      1 wild-type (+/+) (n = 53), Cav-1 heterozygous (+/-) (n = 70), and Cav-1 knockout
      (-/-) (n = 57) animals, and monitored their long-term survival over a 2 year
      period. Here, we show that Cav-1 null (-/-) mice exhibit an approximately 50%
      reduction in life span, with major declines in viability occurring between 27 and
      65 weeks of age. However, Cav-1 heterozygous (+/-) mice did not show any changes
      in long-term survival, indicating that loss of both Cav-1 alleles is required to
      mediate a reduction in life span. Mechanistically, these dramatic reductions in
      life span appear to be secondary to a combination of pulmonary fibrosis,
      pulmonary hypertension, and cardiac hypertrophy in Cav-1 null mice. Taken
      together, our results provide the first demonstration that loss of Cav-1 gene
      expression and caveolae organelles dramatically affects the long-term survival of
      an organism. In addition, aged Cav-1 null mice may provide a new animal model to
      study the pathogenesis and treatment of progressive hypertrophic cardiomyopathy
      and sudden cardiac death syndrome.

PMID- 14690423
TI  - Correlation between the activities and the oligomeric forms of pig gastric H/K
      ATPase.
AB  - Membrane-bound H/K-ATPase was solubilized by octaethylene glycol dodecyl ether
      (C(12)E(8)) or n-octyl glucoside (nOG). H/K-ATPase activity and the distribution
      of protomeric and oligomeric components were evaluated by high-performance gel
      chromatography (HPGC) and by single-molecule detection using total internal
      reflection fluorescence microscopy (TIRFM). As evidenced by HPGC of the C(12)E(8)
      solubilized enzyme, the distribution of oligomers was 12% higher oligomeric, 44%
      diprotomeric, and 44% protomeric species, although solubilization by C(12)E(8)
      reduced the H/K-ATPase activity to 1.8% of that of the membrane-bound enzyme. The
      electron microscopic images of the C(12)E(8)-solubilized enzyme showed the
      presence of protomers and a combination of two and more protomers. While the nOG
      solubilized H/K-ATPase retained the same turnover number and 71% of the specific
      activity as that of the membrane-bound enzyme, 56% higher oligomeric, 34%
      diprotomeric, and 10% protomeric species were detected. TIRFM analysis of
      solubilized fluorescein 5'-isothiocyanate (FITC)-modified H/K-ATPase at Lys-518
      of the alpha-chain showed a quantized photobleaching of the FITC fluorescence
      intensity. For the C(12)E(8)-solubilized FITC-enzyme, the fraction of each of the
      initial relative fluorescence intensity units of 4, 2, and 1 was, respectively,
      5%, 44% and 51%. In the case of the nOG-solubilized FITC-enzyme, each fraction of
      4 and 2 units was, respectively, 54% and 46% with no detectable 1 unit fraction.
      This represents the first direct observation of H/K-ATPase in aqueous solution.
      The correlation between the enzymatic activities and distribution of oligomeric
      forms of H/K-ATPase by HPGC and the observation of a single molecule of H/K
      ATPase and others suggests that the tetraprotomeric form of H/K-ATPase molecules
      represents the functional species in the membrane.

PMID- 14690424
TI  - Solution structure of the disulfide-linked dimer of human intestinal trefoil
      factor (TFF3): the intermolecular orientation and interactions are markedly
      different from those of other dimeric trefoil proteins.
AB  - The trefoil protein TFF3 forms a homodimer (via a disulfide linkage) that is
      thought to have increased biological activity over the monomer. The solution
      structure of the TFF3 dimer has been determined by NMR and compared with the
      structure of the TFF3 monomer and with other trefoil dimer structures (TFF1 and
      TFF2). The most significant structural differences between the trefoil domain in
      the monomer and dimer TFF3 are in the orientations of the N-terminal 3(10)-helix
      (residues 10-12) and in the presence in the dimer of an additional 3(10)-helix
      (residues 53-55) outside of the core region. The TFF3 dimer forms a more compact
      structure as compared with the TFF1 dimer where the two trefoil domains are
      connected by a flexible region with the monomer units being at variable distances
      from each other and in many different orientations. Although TFF2 is also a
      compact structure, the dispositions of its monomer units are very different from
      those of TFF3. The structural differences between the dimers result in the two
      putative receptor/ligand binding sites that remain solvent exposed in the dimeric
      structures having very different dispositions in the different dimers. Such
      differences have significant implications for the mechanism of action and
      functional specificity for the TFF class of proteins.

PMID- 14690425
TI  - The crystal structure of Pichia pastoris lysyl oxidase.
AB  - Pichia pastoris lysyl oxidase (PPLO) is unique among the structurally
      characterized copper amine oxidases in being able to oxidize the side chain of
      lysine residues in polypeptides. Remarkably, the yeast PPLO is nearly as
      effective in oxidizing a mammalian tropoelastin substrate as is a true mammalian
      lysyl oxidase isolated from bovine aorta. Thus, PPLO is functionally related to
      the copper-containing lysyl oxidases despite the lack of any significant sequence
      similarity with these enzymes. The structure of PPLO has been determined at 1.65
      A resolution. PPLO is a homodimer in which each subunit contains a Type II copper
      atom and a topaquinone cofactor (TPQ) formed by the posttranslational
      modification of a tyrosine residue. While PPLO has tertiary and quaternary
      topologies similar to those found in other quinone-containing copper amine
      oxidases, its active site is substantially more exposed and accessible. The
      structural elements that are responsible for the accessibility of the active site
      are identified and discussed.

PMID- 14690426
TI  - Tight binding of deoxyribonucleotide triphosphates to human thymidine kinase 2
      expressed in Escherichia coli. Purification and partial characterization of its
      dimeric and tetrameric forms.
AB  - Human thymidine kinase 2 (hTK2) phosphorylates pyrimidine deoxyribonucleosides to
      the corresponding nucleoside monophosphates, using a nucleotide triphosphate as a
      phosphate donor. In this study, hTK2 was cloned and expressed at high levels in
      Escherichia coli as a fusion protein with maltose-binding protein. Induction of a
      heat-shock response by ethanol and coexpression of plasmid-encoded GroEL/ES
      chaperonins at 28 degrees C minimized the nonspecific aggregation of the hybrid
      protein and improved the recovery of three homooligomeric forms of the properly
      folded enzyme, i.e., dimer > tetramer > hexamer. The dimer and the tetramer were
      isolated in stable and highly purified forms after proteolytic removal of the
      fusion partner. Both oligomers contained a substoichiometric amount of
      deoxyribonucleotide triphosphates (dTTP > dCTP > dATP), known to be strong
      feedback inhibitors of the enzyme. Steady-state kinetic studies were consistent
      with the presence of endogenous inhibitors, and both oligomeric forms revealed a
      lag phase of at least approximately 5 min, which was abolished on preincubation
      with substrate (dThd or dCyd). The rather similar kinetic properties of the two
      oligomeric forms indicate that the basic functional unit is a dimer. Molecular
      docking experiments with a modeled hTK2 three-dimensional structure accurately
      predicted the binding positions at the active site of the natural substrates
      (dThd, dCyd, and ATP) and inhibitors (dTTP and dCTP), with highly conserved
      orientations obtained for all ligands. The calculated relative nonbonded
      interaction energies are in agreement with the biochemical data and show that the
      inhibitor complexes have lower stabilization energies (higher affinity) than the
      substrates.

PMID- 14690427
TI  - Detection of alpha-helical coiled-coil dimer formation by spin-labeled synthetic
      peptides: a model parallel coiled-coil peptide and the antiparallel coiled coil
      formed by a replica of the ProP C-terminus.
AB  - Electron paramagnetic resonance spectroscopy was used to determine relative
      peptide orientation within homodimeric, alpha-helical coiled-coil structures.
      Introduction of cysteine (Cys) residues into peptides/proteins for spin labeling
      allows detection of their oligomerization from exchange broadening or dipolar
      interactions between residues within 25 A of each other. Two synthetic peptides
      containing Cys substitutions were used: a 35-residue model peptide and the 30
      residue ProP peptide. The model peptide is known to form a stable, parallel
      homodimeric coiled coil, which is partially destabilized by Cys substitutions at
      heptad a and d positions (peptides C30a and C33d). The ProP peptide, a 30-residue
      synthetic peptide, corresponds to residues 468-497 of osmoregulatory transporter
      ProP from Escherichia coli. It forms a relatively unstable, homodimeric coiled
      coil that is predicted to be antiparallel in orientation. Cys was introduced in
      heptad g positions of the ProP peptide, near the N-terminus (K473C, creating
      peptide C473g) or closer to the center of the sequence (E480C, creating peptide
      C480g). In contrast to the destabilizing effect of Cys substitution at the core
      heptad a or d positions of model peptides C30a and C33d, circular dichroism
      spectroscopy showed that Cys substitutions at the heptad g positions of the ProP
      peptide had little or no effect on coiled-coil stability. Thermal denaturation
      analysis showed that spin labeling increased the stability of the coiled coil for
      all peptides. Strong exchange broadening was detected for both C30a and C33d, in
      agreement with a parallel structure. EPR spectra of C480g had a large hyperfine
      splitting of about 90 G, indicative of strong dipole-dipole interactions and a
      distance between spin-labeled residues of less than 9 A. Spin-spin interactions
      were much weaker for C473g. These results supported the hypothesis that the ProP
      peptide primarily formed an antiparallel coiled coil, since formation of a
      parallel dimer should result in similar spin-spin interactions for the spin
      labeled Cys at both sites.

PMID- 14690428
TI  - Spectroscopic and kinetic properties of recombinant choline oxidase from
      Arthrobacter globiformis.
AB  - Choline oxidase catalyzes the four-electron oxidation of choline to glycine
      betaine, with molecular oxygen acting as primary electron acceptor. Recently, the
      recombinant enzyme expressed in Escherichia coli was purified to homogeneity and
      shown to contain FAD in a mixture of oxidized and anionic semiquinone redox
      states [Fan et al. (2003) Arch. Biochem. Biophys., in press]. In this study,
      methods have been devised to convert the enzyme-bound flavin semiquinone to
      oxidized FAD and vice versa, allowing characterization of the resulting forms of
      choline oxidase. The enzyme-bound oxidized flavin showed typical UV-vis
      absorbance peaks at 359 and 452 nm (with epsilon(452) = 11.4 M(-1) cm(-1)) and
      emitted light at 530 nm (with lambda(ex) at 452 nm). The affinity of the enzyme
      for sulfite was high (with a K(d) value of approximately 50 microM at pH 7 and 15
      degrees C), suggesting the presence of a positive charge near the N(1)C(2)=O
      locus of the flavin. The enzyme-bound anionic flavin semiquinone was unusually
      insensitive to oxygen or ferricyanide at pH 8 and showed absorbance peaks at 372
      and 495 nm (with epsilon(372) = 19.95 M(-1) cm(-1)), maximal fluorescence
      emission at 454 nm (with lambda(ex) at 372 nm), circular dichroic signals at 370
      and 406 nm, and an ESR peak-to-peak line width of 13.9 G. Both UV-vis absorbance
      studies on the enzyme under turnover with choline and steady-state kinetic data
      with either choline or betaine aldehyde were consistent with the flavin
      semiquinone being not involved in catalysis. The pH dependence of the kinetic
      parameters at varying concentrations of both choline and oxygen indicated that a
      catalytic base is required for choline oxidation but not for oxygen reduction and
      that the order of the kinetic steps involving substrate binding and product
      release is not affected by pH.

PMID- 14690429
TI  - Spectrophotometric and steady-state kinetic analysis of the biosynthetic arginine
      decarboxylase of Yersinia pestis utilizing arginine analogues as inhibitors and
      alternative substrates.
AB  - The PLP-dependent, biosynthetic arginine decarboxylase (ADC) of Yersinia pestis
      was investigated using steady-state kinetics employing structural analogues of
      arginine as both alternative substrates and competitive inhibitors. The inhibitor
      analysis indicates that binding of the carboxyl and guanidinium groups of the
      substrate, l-arginine, provides essentially all of the free energy change
      realized upon substrate binding in the ground state. Furthermore, recognition of
      the guanidinium group is primarily responsible for substrate specificity.
      Comparison of the steady-state parameters for a series of alternative substrates
      that contained chemically modified guanidinium moieties provides evidence of a
      role for induced fit in ADC catalysis. ADC was also characterized by UV/vis and
      fluorescence spectrophotometry in the presence or absence of a number of arginine
      analogues. The enzyme complexes formed served as models for the adsorption
      complex and the external aldimine complex of the enzyme with the substrate.

PMID- 14690430
TI  - Intramolecular dephosphorylation of ERK by MKP3.
AB  - The dual specificity mitogen-activated protein kinase phosphatase MKP3
      downregulates mitogenic signaling through dephosphorylation of extracellular
      signal-regulated kinase (ERK). Like other MKPs, MKP3 consists of a noncatalytic N
      terminal domain and a catalytic C-terminal domain. ERK binding to the N-terminal
      noncatalytic domain of MKP3 has been shown to increase (up to 100-fold) the
      catalytic activity of MKP3 toward small artificial substrates. Here, we address
      the function of the N-terminal domain of MKP3 in either inter- or intramolecular
      dephosphorylation of pERK (phosphorylated ERK) and the stoichiometry of the
      MKP3/pERK Michaelis complex. These are important mechanistic distinctions given
      the observation that ERK exists in a monomer/dimer equilibrium that is shifted
      toward the dimer when phosphorylated and given that MKP3 undergoes catalytic
      activation toward other substrates when bound to ERK. Wild-type and engineered
      mutants of ERK and MKP3, binding analyses, reaction kinetics, and chemical cross
      linking studies were used to demonstrate that the monomer of MKP3 binds to the
      monomeric form of pERK and that MKP3 within the resulting heterodimer performs
      intramolecular dephosphorylation of pERK. This study provides the first direct
      evidence that MKP3 utilizes intramolecular dephosphorylation between a complex
      consisting of one molecule each of MKP3 and ERK. Catalytic activation and
      substrate tethering by MKP3 lead to a >or=4000-fold rate enhancement
      (k(cat)/K(m)) for dephosphorylation of pERK.

PMID- 14690431
TI  - Solvent and primary deuterium isotope effects show that lactate CH and OH bond
      cleavages are concerted in Y254F flavocytochrome b2, consistent with a hydride
      transfer mechanism.
AB  - Yeast flavocytochrome b(2) catalyzes the oxidation of lactate to pyruvate;
      because of the wealth of structural and mechanistic information available, this
      enzyme has served as the model for the family of flavoproteins catalyzing
      oxidation of alpha-hydroxy acids. Primary deuterium and solvent isotope effects
      have now been used to analyze the effects of mutating the active site residue
      Tyr254 to phenylalanine. Both the V(max) and the V/K(lactate) values decrease
      about 40-fold in the mutant enzyme. The primary deuterium isotope effects on the
      V(max) and the V/K(lactate) values increase to 5.0, equivalent to the intrinsic
      isotope effect for the wild-type enzyme. In addition, both the V(max) and the
      V/K(lactate) values exhibit solvent isotope effects of 1.5. Measurement of the
      solvent isotope effect with deuterated lactate establishes that the primary and
      solvent isotope effects arise from the same chemical step, consistent with
      concerted cleavage of the lactate OH and CH bonds. The pH dependence of the
      mutant enzyme is not significantly different from that of the wild-type enzyme;
      this is most consistent with a requirement that the side chain of Tyr254 be
      uncharged for catalysis. The results support a hydride transfer mechanism for the
      mutant protein and, by extension, wild-type flavocytochrome b(2) and the other
      flavoproteins catalyzing oxidation of alpha-hydroxy acids.

PMID- 14690432
TI  - Engineering sialic acid synthetic ability into insect cells: identifying
      metabolic bottlenecks and devising strategies to overcome them.
AB  - Previous studies have indicated negligible levels of both sialylation and the
      precursor N-acetylneuraminic acid (Neu5Ac) in a number of insect cell lines grown
      in serum-free medium. The overexpression of the human sialic acid 9-phosphate
      synthase (SAS) in combination with N-acetylmannosamine (ManNAc) feeding has been
      shown to overcome this limitation. In this study we evaluated the potential
      bottlenecks in the sialic acid synthesis pathway in a Spodoptera frugiperda (Sf9)
      insect cell line and devised strategies to overcome them by overexpression of the
      enzymatic pathway enzymes combined with appropriate substrate feeding.
      Coexpression of SAS and UDP-GlcNAc 2-epimerase/ManNAc kinase, the bifunctional
      enzyme initiating sialic acid biosynthesis in mammals, resulted in Neu5Ac
      synthesis without use of any external media supplementation to demonstrate that
      Neu5Ac could be generated intracellularly in Sf9 cells using natural metabolic
      precursors. N-Acetylglucosamine (GlcNAc) feeding in combination with this
      coexpression resulted in much higher levels of Neu5Ac compared to levels obtained
      with ManNAc feeding with SAS expression alone. The lower Neu5Ac levels obtained
      with ManNAc feeding suggested limitations in the transport and phosphorylation of
      ManNAc. The bottleneck in phosphorylation was likely due to utilization of GlcNAc
      kinase for phosphorylation of ManNAc in insect cells and was overcome by
      expression of ManNAc kinase. The transport limitation was addressed by the
      addition of tetra-O-acetylated ManNAc, which is easily taken up by the cells. An
      alternative sialic acid, 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN),
      could also be generated in insect cells, suggesting the potential for controlling
      not only the production of sialic acids but also the type of sialic acid
      generated. The levels of KDN could be increased with virtually no Neu5Ac
      generation when Sf9 cells were fed excess GlcNAc. The results of these studies
      may be used to enhance the sialylation of target glycoproteins in insect and
      other eukaryotic expression systems.

PMID- 14690433
TI  - Interactions of the QacR multidrug-binding protein with structurally diverse
      ligands: implications for the evolution of the binding pocket.
AB  - The QacR multidrug-binding repressor protein regulates the expression of the
      Staphylococcus aureus qacA gene, a multidrug resistance (MDR) locus that is
      prevalent in clinical isolates of this important human pathogen. In this paper we
      demonstrate that the range of structurally diverse compounds capable of inducing
      qacA transcription is significantly more varied than previously appreciated,
      particularly in relation to bivalent cations. For all of the newly identified
      inducing compounds, induction of qacAexpression was correlated with a matching
      ability to dissociate QacR from operator DNA. Development of a ligand-binding
      assay based on intrinsic tryptophan fluorescence permitted dissociation constants
      to be determined for the majority of known QacR ligands, with values ranging from
      0.2 to 82 microM. High-affinity binding of a compound to QacR in vitro was not
      found to correlate very strongly with either its in vivo inducing abilities or
      its structure. The latter observation indicated that the QacR ligand-binding
      pocket appears to have evolved to accommodate a wide range of toxic hydrophobic
      cations, rather than a specific class of compound. Importantly, the antimicrobial
      ligands of QacR included several plant alkaloids that share structural
      similarities with synthetic MDR substrates. This is consistent with the
      suggestion that the qacA-qacR MDR locus was recently derived from genes that
      protect against natural antimicrobial compounds.

PMID- 14690434
TI  - Human Rad52 facilitates a three-stranded pairing that follows no strand exchange:
      a novel pairing function of the protein.
AB  - Human Rad52 protein, by analogy with the genetics of yeast Rad52, is believed to
      mediate a pathway of homologous recombination even independent of Rad51. Current
      study is focused on unraveling the molecular properties of hRad52 that endow the
      protein such an ability. We show here that the hRad52 protein binds single
      stranded DNA (ssDNA) as well as 3'- and 5'-tailed duplexes severalfold better
      than blunt-ended duplexes, altering the sensitivity of the bound DNA to the
      action of DNase I. Protein binding is sensitive to the length of the ssDNA:
      targets as short as a 33mer poorly bind the protein, whereas that of a 61mer and
      above bind the protein stably well. Such stable ssDNA-hRad52 complexes are highly
      competent in mediating not only the annealing of two complementary strands but
      also three-stranded pairing. The latter involves homologous recognition of linear
      duplex DNA by the ssDNA-hRad52 complex. We show that the hRad52 protein
      facilitates homologous recognition between ssDNA and duplex-DNA through a process
      that involves unwinding or transient unpairing of the interacting duplex via a
      novel three-stranded intermediate that does not lead to strand exchange. The
      results enable us to visualize a novel role for hRad52 that may model its
      function in a pathway requiring no hRad51.

PMID- 14690435
TI  - Characterization of deoxyribozymes that synthesize branched RNA.
AB  - We recently reported deoxyribozymes (DNA enzymes) that synthesize 2',5'-branched
      RNA. The in vitro-selected 9F7 and 9F21 deoxyribozymes mediate reaction of a
      branch-site adenosine 2'-hydroxyl on one RNA substrate with the 5'-triphosphate
      of another RNA substrate. Here we characterize these DNA enzymes with respect to
      their branch-forming activity. Both 9F7 and 9F21 are much more active with Mn(2+)
      than with Mg(2+). The K(d,app)(Mg(2+)) > 400 mM but K(d,app)(Mn(2+))
      approximately 20-50 mM, and the ligation rates k(obs) are orders of magnitude
      faster with Mn(2+) than with Mg(2+) (e.g., 9F7 approximately 0.3 min(-1) with 20
      mM Mn(2+) versus 0.4 h(-1) with 100 mM Mg(2+), both at pH 7.5 and 37 degrees C).
      Of the other tested transition metal ions Zn(2+), Ni(2+), Co(2+), and Cd(2+),
      only Co(2+) supports a trace amount of activity. 9F7 is more tolerant than 9F21
      of varying the RNA substrate sequences. For the RNA substrate that donates the
      adenosine 2'-hydroxyl, 9F7 requires YUA, where Y = pyrimidine and A is the branch
      site. The 3'-tail emerging from the branch-site A may have indefinite length, but
      it must be at least one nucleotide long for high activity. The 5'-triphosphate
      RNA substrate requires several additional nucleotides with varying sequence
      requirements (5'-pppGRMWR). Outside of these regions that flank the ligation
      site, 9F7 and 9F21 tolerate any RNA substrate sequences via Watson-Crick
      covariation of the DNA binding arms that interact directly with the substrates.
      9F7 provides a high yield of 2',5'-branched RNA on the preparative nanomole
      scale. The ligation reaction is effectively irreversible; the pyrophosphate
      leaving group in the ligation reaction does not induce 2',5'-cleavage, and
      pyrophosphate does not significantly inhibit ligation except in 1000-fold excess.
      Deleting a specific nucleotide in one of the DNA binding arms near the ligation
      junction enhances ligation activity, suggesting an interesting structure near
      this region of the deoxyribozyme-substrate complex. These data support the
      utility of deoxyribozymes in creating synthetic 2',5'-branched RNAs for
      investigations of group II intron splicing, debranching enzyme (Dbr) activity,
      and other biochemical reactions.

PMID- 14690436
TI  - Two 14-3-3 binding motifs are required for stable association of Forkhead
      transcription factor FOXO4 with 14-3-3 proteins and inhibition of DNA binding.
AB  - The 14-3-3 proteins, a family of dimeric regulatory proteins, are involved in
      many biologically important processes. The common feature of 14-3-3 proteins is
      their ability to bind to other proteins in a phosphorylation-dependent manner.
      Through these binding interactions, 14-3-3 proteins work as molecular scaffolds,
      modulating the biological functions of their partners. 14-3-3 proteins recognize
      short motifs containing a phosphorylated serine or threonine residue. In this
      study, we have quantitatively characterized the in vitro interactions among 14-3
      3, the Forkhead transcription factor FOXO4, and its target DNA, the insulin
      response element. Phosphorylation of FOXO4 (residues 11-213) by protein kinase B
      at Thr-28 and Ser-193 creates two 14-3-3 binding motifs. Analytical gel
      filtration and sedimentation equilibrium experiments indicate that doubly
      phosphorylated FOXO4 and 14-3-3zeta form a complex with 1:2 molar stoichiometry
      and a K(D) of less than 30 nM. In contrast, singly phosphorylated FOXO4 mutants
      bind 14-3-3zeta with significantly lower affinity while retaining the ability to
      bind DNA. An active role for 14-3-3 in the disassembly of the FOXO4/DNA complex
      is demonstrated by the fact that, in the presence of 14-3-3, two phosphorylated
      14-3-3 binding motifs are needed for the complete inhibition of FOXO4 binding to
      its target DNA.

PMID- 14690437
TI  - Differential mechanisms for calcium-dependent protein/membrane association as
      evidenced from SPR-binding studies on supported biomimetic membranes.
AB  - In this work, two different types of supported biomimetic membranes were designed
      to study the membrane binding properties of two different proteins that both
      interact with cellular membranes in a calcium-dependent manner. The first one,
      neurocalcin, is a member of a subfamilly of EF-hand calcium-binding proteins that
      exhibit a calcium-myristoyl switch. The second protein is a bacterial toxin, the
      adenylate cyclase produced by Bordetella pertussis, the causative agent of
      whooping cough. The biomimetic membranes constructed in this study were either
      hybrid bilayer membranes or polymer-tethered membranes. Hemimembrane formation
      was obtained in two steps: a monolayer of 1-octadecanethiol or
      octadecyltrichlorosilane was self-assembled on top of the gold or glass surface,
      respectively, and then the egg-phosphatidyl choline (PC) vesicle fused on the
      hydrophobic alkyl layer. Polymer-tethered membranes on solid support were
      obtained using N-hydroxysuccinimide (NHS)-terminated-poly(ethyleneglycol) (PEG)
      phospholipids as anchoring molecules. Egg-PC/1,2-distearoyl-sn-glycero-3-phospho
      ethanolamine-poly(ethyleneglycol)-N-hydroxy-succinimide (DSPE-PEG-NHS) mixture
      liposomes were injected on the top of an amine grafted surface (cysteamine-coated
      gold or silanized glass); vesicles were linked to the surface and disrupted,
      leading to the formation of a bilayer. The biomimetic membrane constructions were
      followed by surface plasmon spectroscopy, while membrane fluidity and continuity
      were observed by fluorescence microscopy. Protein/membrane binding properties
      were determined by resonance surface plasmon measurements. The tethered bilayer,
      designed here, is very versatile as it can be adapted easily to different types
      of support. The results demonstrate the potentialities of such polymer-tethered
      artificial membranes for the study of proteins that insert into biological
      membranes such as toxins and/or integral membrane proteins.

PMID- 14690438
TI  - Cellular uptake of Clostridium botulinum C2 toxin: membrane translocation of a
      fusion toxin requires unfolding of its dihydrofolate reductase domain.
AB  - The Clostridium botulinum C2 toxin is the prototype of the family of binary actin
      ADP-ribosylating toxins. C2 toxin is composed of two separated nonlinked
      proteins. The enzyme component C2I ADP-ribosylates actin in the cytosol of target
      cells. The binding/translocation component C2II mediates cell binding of the
      enzyme component and its translocation from acidic endosomes into the cytosol.
      After proteolytic activation, C2II forms heptameric pores in endosomal membranes,
      and most likely, C2I translocates through these pores into the cytosol. For this
      step, the cellular heat shock protein Hsp90 is essential. We analyzed the effect
      of methotrexate on the cellular uptake of a fusion toxin in which the enzyme
      dihydrofolate reductase (DHFR) was fused to the C-terminus of C2I. Here, we
      report that unfolding of C2I-DHFR is required for cellular uptake of the toxin
      via the C2IIa component. The C2I-DHFR fusion toxin catalyzed ADP-ribosylation of
      actin in vitro and was able to intoxicate cultured cells when applied together
      with C2IIa. Binding of the folate analogue methotrexate favors a stable three
      dimensional structure of the dihydrofolate reductase domain. Pretreatment of C2I
      DHFR with methotrexate prevented cleavage of C2I-DHFR by trypsin. In the presence
      of methotrexate, intoxication of cells with C2I-DHFR/C2II was inhibited. The
      presence of methotrexate diminished the translocation of the C2I-DHFR fusion
      toxin from endosomal compartments into the cytosol and the direct C2IIa-mediated
      translocation of C2I-DHFR across cell membranes. Methotrexate had no influence on
      the intoxication of cells with C2I/C2IIa and did not alter the C2IIa-mediated
      binding of C2I-DHFR to cells. The data indicate that methotrexate prevented
      unfolding of the C2I-DHFR fusion toxin, and thereby the translocation of
      methotrexate-bound C2I-DHFR from endosomes into the cytosol of target cells is
      inhibited.

PMID- 14690439
TI  - Natural monomeric form of fetal bovine serum acetylcholinesterase lacks the C
      terminal tetramerization domain.
AB  - Acetylcholinesterase isolated from fetal bovine serum (FBS AChE) was previously
      characterized as a globular tetrameric form. Analysis of purified preparations of
      FBS AChE by gel permeation chromatography revealed the presence of a stable,
      catalytically active, monomeric form of this enzyme. The two forms could be
      distinguished from each other based on their molecular weight, hydrodynamic
      properties, kinetic properties, thermal stability, and the type of glycans they
      carry. No differences between the two forms were observed for the binding of
      classical inhibitors such as edrophonium and propidium or inhibitors that are
      current or potential drugs for the treatment of Alzheimer's disease such as (-)
      huperzine A and E2020; tacrine inhibited the monomeric form 2-3-fold more
      potently than the tetrameric form. Sequencing of peptides obtained from an in-gel
      tryptic digest of the monomer and tetramer by tandem mass spectrometry indicated
      that the tetramer consists of 583 amino acid residues corresponding to the mature
      form of the enzyme, whereas the monomer consists of 543-547 amino acid residues.
      The subunit molecular weight of the protein component of the monomer (major
      species) was determined to be 59 414 Da and that of the tetramer as 64 239 Da.
      The N-terminal of the monomer and the tetramer was Glu, suggesting that the
      monomer is not a result of truncation at the N-terminal. The only differences
      detected were at the C-terminus. The tetramer yielded the expected C-terminus,
      CSDL, whereas the C-terminus of the monomer yielded a mixture of peptides, of
      which LLSATDTLD was the most abundant. These results suggest that monomeric FBS
      AChE is trimmed at the C-terminus, and the results are consistent with the
      involvement of C-terminal amino acids in the assembly of monomers into tetramers.

PMID- 14690440
TI  - An FHA phosphoprotein recognition domain mediates protein EmbR phosphorylation by
      PknH, a Ser/Thr protein kinase from Mycobacterium tuberculosis.
AB  - In bacteria, regulatory phosphorylation of proteins at serine and/or threonine
      residues by Ser/Thr protein kinase (STPK) is an emerging theme in prokaryotic
      signaling, particularly since the prediction of the occurrence of several STPKs
      from genome sequencing and sequence surveys. Here we show that protein PknH
      possesses an autokinase activity and belongs to the large STPK family found in
      Mycobacterium tuberculosis. Evidence is presented that PknH can also
      phosphorylate EmbR, a protein suspected to modulate the level of
      arabinosyltransferase activity involved in arabinan biosynthesis of
      arabinogalactan, a key molecule of the mycobacterial cell wall. Interestingly,
      EmbR possesses an FHA (forkhead-associated) domain, a newly described
      phosphoprotein recognition domain, which plays an essential role in PknH-EmbR
      interaction and phosphorylation of EmbR by PknH. It is demonstrated that mutation
      of each of three particular residues of this FHA domain, Arg312, Ser326, and
      Asn348, totally abolishes the PknH-mediated phosphorylation of EmbR, thus
      highlighting the critical role of this domain in the direct interaction between
      EmbR and PknH.

PMID- 14690441
TI  - Modified alpha A crystallin in the retina: altered expression and truncation with
      aging.
AB  - Crystallins are small heat shock proteins with chaperone function that prevent
      heat- and oxidative stress-induced aggregation of proteins. This is the first
      report describing modifications of alphaA crystallin in the sensory retina,
      including altered content and truncation with aging. Proteins from adult, middle
      age, and old Fischer 344 Brown Norway rats were compared. Western immunoblotting
      was used to evaluate alphaA crystallin content and identify protein spots on two
      dimensional gels containing alphaA crystallin. The type and site of multiple post
      translational modifications were identified by mass spectrometry. We found the
      content of alphaA crystallin was significantly decreased in the oldest rats. On
      two-dimensional gels, retinal crystallins resolved into multiple spots with
      altered migration, indicative of changes in intrinsic charge and/or truncation.
      Post-translational modifications that were identified included oxidation,
      phosphorylation, deamidation, acetylation, and truncation. In samples from rats
      of all ages, a highly modified N-terminus containing these modifications was
      found. We also observed an age-dependent difference in the extent of N- and C
      terminal truncation. These results suggest that protection against stress-induced
      protein aggregation is compromised in the aged retina.

PMID- 14690442
TI  - Residue 219 impacts on the dynamics of the C-terminal region in glutathione
      transferase A1-1: implications for stability and catalytic and ligandin
      functions.
AB  - The C-terminal region in class alpha glutathione transferases (GSTs) modulates
      the catalytic and nonsubstrate ligand binding functions of these enzymes. Except
      for mouse GST A1-1 (mGST A1-1), the structures of class alpha GSTs have a bulky
      aliphatic side chain topologically equivalent to Ile219 in human GST A1-1 (hGST
      A1-1). In mGST A1-1, the corresponding residue is an alanine. To investigate the
      role of Ile219 in determining the conformational dynamics of the C-terminal
      region in hGST A1-1, the residue was replaced by alanine. The substitution had no
      effect on the global structure of hGST A1-1 but did reduce the conformational
      stability of the C-terminal region of the protein. This region could be
      stabilized by ligands bound at the active site. The catalytic behavior of hGST A1
      1 was significantly compromised by the I219A mutation as demonstrated by reduced
      enzyme activity, increased K(m) for the substrates glutathione (GSH) and 1-chloro
      2,4-dinitrobenzene (CDNB), and reduced catalytic efficiencies. Inhibition studies
      also indicated that the binding affinities for product and substrate analogues
      were dramatically decreased. The affinity of the mutant for GSH was, however,
      only slightly increased, indicating that the G-site was unaltered by the
      mutation. The binding affinity and stoichiometry for the anionic dye 8-anilino-1
      naphthalene sulfonate (ANS) was also not significantly affected by the I219A
      mutation. However, the lower DeltaC(p) for ANS binding to the mutant (-0.34
      kJ/mol per K compared with -0.84 kJ/mol per K for the wild-type protein) suggests
      that ANS binding to the mutant results in the burial of less hydrophobic surface
      area. Fluorescence data also indicates that ANS bound to the mutant is more prone
      to quenching by water. Overall, the data from this study, together with the
      structural details of the C-terminal region in mGST A1-1, show that Ile219 is an
      important structural determinant of the stability and dynamics of the C-terminal
      region of hGST A1-1.

PMID- 14690443
TI  - Recombinant expression, purification, and comparative characterization of torsinA
      and its torsion dystonia-associated variant Delta E-torsinA.
AB  - Early-onset torsion dystonia is an autosomal dominant movement disorder that has
      been linked to the deletion of one of a pair of glutamic acid residues in the
      protein torsinA (E(302/303); DeltaE-torsinA). In transfected cells, DeltaE
      torsinA exhibits similar biochemical properties to wild type (WT)-torsinA, but
      displays a distinct subcellular localization. Primary structural analysis of
      torsinA suggests that this protein is a membrane-associated member of the AAA
      family of ATP-binding proteins. However, to date, neither WT- nor DeltaE-torsinA
      has been obtained in sufficient quantity and purity to permit detailed
      biochemical and biophysical characterization. Here, we report a baculovirus
      expression system that provides milligram quantities of purified torsin proteins.
      Recombinant WT- and DeltaE-torsinA were found to be membrane-associated
      glycoproteins that required detergents for solubilization and purification.
      Analysis of the biophysical properties of WT- and DeltaE-torsinA indicated that
      both proteins were folded monomers in solution that exhibited equivalent
      denaturation behaviors under thermal and chaotropic (guanidinium chloride)
      stress. Additionally, both forms of torsinA were found to display ATPase activity
      with similar k(cat) and K(m) values. Collectively, these data reveal that torsinA
      is a membrane-associated ATPase and indicate that the DeltaE(302/303) dystonia
      associated mutation in this protein does not cause gross changes in its catalytic
      or structural properties. These findings are consistent with a disease mechanism
      in which DeltaE-torsinA promotes dystonia through a gain rather than loss of
      function. The recombinant expression system for torsinA proteins described herein
      should facilitate further biochemical and structural investigations to test this
      hypothesis.

PMID- 14690444
TI  - 1H NMR structural characterization of the cytochrome c modifications in a
      micellar environment.
AB  - The interaction of cytochrome c with micelles of sodium dodecyl sulfate was
      studied by proton NMR spectroscopy. The protein/micelles ratio was found to be
      crucial in controlling the extent of the conformational changes in the heme
      crevice. Over a range of ratios between 1:30 and 1:60, the NMR spectra of the
      ferric form display no paramagnetic signals due to a moderately fast exchange
      between intermediate species on the NMR time scale. This is consistent with an
      interconversion of bis-histidine derivatives (His18-Fe-His26 and His18-Fe-His33).
      Further addition of micelles induces a high-spin species that is proposed to
      involve pentacoordinated iron. The resulting free binding site, also encountered
      in the ferrous form, is used to complex exogenous ligands such as cyanide or
      carbon monoxide. Attribution of the heme methyls was performed by means of
      exchange spectroscopy through ligand exchange or electron transfer. The heme
      methyl shift pattern of the micellar cyanocytochrome in the ferric low spin form
      is different from the pattern of both the native and the cyanide cytochrome c
      adduct, in the absence of micelles, reflecting a complete change of the heme
      electronic structure. Analysis of the electron self-exchange reaction between the
      two redox states of the micellar cyanocytochrome c yields a rate constant of 2.4
      x 10(4) M(-1) s(-1) at 298 K, which is surprisingly close to the value observed
      in the native protein.

PMID- 14690445
TI  - Stress-induced apoptosis in Spodoptera frugiperda (Sf9) cells: baculovirus p35
      mitigates eIF2 alpha phosphorylation.
AB  - Spodoptera frugiperda (Sf9) ovarian cells, natural hosts for baculovirus, are
      good model systems to study apoptosis and also heterologous gene expression. We
      report that uninfected Sf9 cells readily undergo apoptosis and show increased
      phosphorylation of the alpha subunit of eukaryotic initiation factor 2
      (eIF2alpha) in the presence of agents such as UVB light, etoposide, high
      concentrations of cycloheximide, and EGTA. In contrast, tunicamycin, A23187, and
      low concentrations of cycloheximide promoted eIF2alpha phosphorylation in Sf9
      cells but without apoptosis. These findings therefore suggest that increased
      eIF2alpha phosphorylation does not always necessarily lead to apoptosis, but it
      is a characteristic hallmark of stressed cells and also of cells undergoing
      apoptosis. Cell death induced by the above agents was abrogated by infection of
      Sf9 cells with wild-type (wt) AcNPV. In contrast, Sf9 cells when infected with
      vAcdelta35, a virus carrying deletion of the antiapoptotic p35 gene, showed
      increased apoptosis and enhanced eIF2alpha phosphorylation. Further, a
      recombinant wt virus vAcS51D expressing human S51D, a phosphomimetic form of
      eIF2alpha, induced apoptosis in UVB pretreated Sf9 cells. However, infection with
      vAcS51A expressing a nonphosphorylatable form (S51A) of human eIF2alpha partially
      reduced apoptosis. Consistent with these findings, it has been observed here that
      caspase activation has led to increased eIF2alpha phosphorylation, while caspase
      inhibition by z-VAD-fmk reduced eIF2alpha phosphorylation selectively in cells
      exposed to proapoptotic agents. These findings therefore suggest that the stress
      signaling pathway determines apoptosis, and caspase activation is a prerequisite
      for increased eIF2alpha phosphorylation in Sf9 cells undergoing apoptosis. The
      findings also reinforce the conclusion for the first time that the "pancaspase
      inhibitor" baculovirus p35 mitigates eIF2alpha phosphorylation.

PMID- 14690446
TI  - Glutamate 346 of human Na+-H+ exchanger NHE1 is crucial for modulating both the
      affinity for Na+ and the interaction with amiloride derivatives.
AB  - A NHE1 variant that exhibits very high resistance to (3-methyl sulfonyl-4
      piperidinobenzoyl) guanidine methane sulfonate (HOE694), a potent inhibitor of
      Na(+)-H(+) exchangers, was selected and characterized. Sequencing of the coding
      region corresponding to the N-terminal domain of this variant revealed the
      presence of only one mutation located within membrane-spanning segment 9 (M9).
      This base pair change replaces a glutamate (Glu) with an aspartate (Asp). We
      reproduced this amino acid change in wild-type NHE1 and found that this mutation
      alone is responsible for the huge decrease in sensitivity to the HOE694 compound
      and to ethylisopropylamiloride (EIPA). We found that the NHE1-Glu(346)Asp mutant
      was more than 2000-fold more resistant to HOE694 and up to 300-fold more
      resistant to EIPA than wild-type NHE1, with the size, rather than the charge, of
      the amino acid in position 346 having the greatest effect. Interestingly, its
      affinity for Na(+) was at least 4-fold lower than that of wild-type NHE1.
      Mutation of amino acids in the vicinity of Glu(346) did not change the
      sensitivity of mutated NHE1 proteins to inhibitors. We suggest there is a direct
      interaction of Glu(346) or involvement of Glu(346) in a coordination site with
      NHE inhibitors and with Na(+).

PMID- 14690447
TI  - Identification of proteins that interact with the central coiled-coil region of
      the human protein kinase NEK1.
AB  - NEK protein kinases are evolutionarily conserved kinases structurally related to
      the Aspergillus nidulans mitotic regulator NIMA. At least nine members of the NEK
      family in vertebrates have been described to date, but for most of them the
      interacting protein partners are unknown. The pleiotropic deleterious effects and
      the formation of kidney cysts caused by NEK1 mutation in mice emphasize its
      involvement in the regulation of diverse cellular processes and in the etiology
      of polycystic kidney disease (PKD), respectively. Here we report the
      identification of proteins that interacted with the human NEK1 protein kinase in
      a yeast two-hybrid screen of a human fetal brain cDNA library, using the
      catalytic and regulatory domains of NEK1 separately as baits. These proteins are
      known to take part either in the development of PKD, in the double-strand DNA
      break repair at the G2/M transition phase of the cell cycle, or in neural cell
      development. The proteins involved in PKD include the motor protein KIF3A and the
      proteins tuberin and alpha-catulin. Mapping studies of the human NEK1 regulatory
      domain (NRD) indicated a strong interaction of most of the proteins retrieved
      from the library with putative coiled coils located in the central region of NRD.
      Our results give further support to the previous observation that NEK1 is of
      functional importance for the etiology of PKD.

PMID- 14690448
TI  - Membrane properties induced by anionic phospholipids and phosphatidylethanolamine
      are critical for the membrane binding and catalytic activity of human cytochrome
      P450 3A4.
AB  - Human cytochrome P450 (CYP) 3A4, a membrane anchoring protein, is the major CYP
      enzyme present in both liver and small intestine. The enzyme plays a major role
      in the metabolism of many drugs and procarcinogens. The roles of individual
      phospholipids and membrane properties in the catalytic activity, membrane
      binding, and insertion into the membrane of CYP3A4 are poorly understood. Here we
      report that the catalytic activity of testosterone 6beta-hydroxylation, membrane
      binding, and membrane insertion of CYP3A4 increase as a function of anionic
      phospholipid concentration in the order phosphatidic acid (PA) >
      phosphatidylserine (PS) in a binary system of phosphatidylcholine (PC)/anionic
      phospholipid and as a function of phosphatidylethanolamine (PE) content in
      ternary systems of PC/PE/PA or PC/PE/PS having a fixed concentration of anionic
      phospholipids. These results suggest that PA and PE might help the binding of
      CYP3A4 to the membrane and the interaction with NPR. Cytochrome b(5) (b(5)) and
      apolipoprotein b(5) further enhanced the testosterone 6beta-hydroxylation
      activities of CYP3A4 in all tested phospholipids vesicles with various
      compositions. Phospholipid-dependent changes of the CYP3A4 conformation were also
      revealed by altered Trp fluorescence and CD spectra. We also found that PE
      induced the formation of anionic phospholipid-enriched domains in ternary systems
      using extrinsic fluorescent probes incorporated into lipid bilayers. Taken
      together, it can be suggested that the chemical and physical properties of
      membranes induced by anionic phospholipids and PE are critical for the membrane
      binding and catalytic activity of CYP3A4.

PMID- 14690449
TI  - Probing Ca2+-induced conformational changes in porcine calmodulin by H/D exchange
      and ESI-MS: effect of cations and ionic strength.
AB  - We applied a new method, "protein-ligand interaction using mass spectrometry,
      titration, and H/D exchange" (PLIMSTEX) [Zhu, M. M. (2003) J. Am. Chem. Soc. 125,
      5252-5253], to determine the conformational changes, binding stoichiometry, and
      binding constants for Ca(2+) interactions with calmodulin (CaM) under varying
      conditions of electrolyte identity and ionic strength. The outcome shows that CaM
      becomes less solvent-accessible and more compact upon Ca(2+)-binding, as revealed
      by the PLIMSTEX curve. The formation of CaM-4Ca species is the biggest
      contributor to the shape of the titration curve, indicating that the formation of
      this species accounts for the largest conformational change in the stepwise
      Ca(2+) binding. The Ca(2+)-binding constants, when comparisons permit, agree with
      those in the literature within a factor of 3. The binding is influenced by ionic
      strength and the presence of other cations, although many of these cations do not
      cause conformational change in apo-CaM. Furthermore, Ca(2+)-saturated CaM
      exhibits larger protection and higher Ca(2+) affinity in media of low rather than
      high ionic strength. Both Ca(2+) and Mg(2+) bind to CaM with different
      affinities, causing different conformational changes. K(+), if it does bind,
      causes no detectable conformational change, and interactions of Ca(2+) with CaM
      in the presence of Li(+), Na(+), and K(+) occur with similar affinities and
      associated changes in solvent accessibility. These metal ion effects point to
      nonspecific rather than competitive binding of alkali-metal ions. The rates of
      deuterium uptake by the various CaM-xCa species follow a three-group (fast,
      intermediate, slow), pseudo-first-order kinetics model. Calcium binding causes
      the number of amide hydrogens to shift from the fast to the slow group. The
      results taken together not only provide new insight into CaM but also indicate
      that both PLIMSTEX and kinetic modeling of H/D exchange data may become general
      methods for probing protein conformations and quantifying protein-ligand
      interactions.

PMID- 14690451
TI  - A stepwise method for the isolation of endothelial cells and smooth muscle cells
      from individual canine coronary arteries.
AB  - Methods for the stepwise isolation of endothelial cells and smooth muscle cells
      from individual canine coronary arteries are described. Both cell types can be
      isolated in pure culture with high yields. Dogs are a common species used in the
      study of atherosclerosis and coronary artery disease. Capacity to isolate
      endothelial cells and smooth muscle cells from individual canine coronary
      arteries should prove useful in the study of coronary artery disease.

PMID- 14690452
TI  - Bovine pituitary extract provides remarkable protection against oxidative stress
      in human prostate epithelial cells.
AB  - Bovine pituitary extract (BPE) is routinely used as a mitogenic supplement in
      serum-free growth medium. In addition to its mitogenic activity, BPE contains a
      variety of growth factors and hormones with reported antioxidant activity. This
      study examines the antioxidant potential of BPE in nontumorigenic human prostate
      epithelial cells (RWPE-1). Treatment of RWPE-1 cells with BPE (50 microg/ml)
      provided significant protection against H(2)O(2)-induced cell death,
      deoxyribonucleic acid fragmentation, protein oxidation, and membrane damage.
      Treatment with heat (71 degrees C, 10 min) and proteolytic enzymes reduced the
      antioxidant activity of BPE, suggesting that proteins present in BPE may be
      responsible for the antioxidant activity. Residual catalase activity present in
      BPE was responsible for a portion (30%) of the antioxidant activity.
      Interestingly, RWPE-1 cells treated with BPE and H(2)O(2) rapidly accumulated
      intracellular reactive oxygen species (ROS) to a greater extent than cells
      receiving only H(2)O(2). Pretreatment of RWPE-1 cells with tyrosine kinase
      inhibitors (genistein, tyrphostin 47, and AG-1296) before the addition of
      H(2)O(2) diminished BPE protection against H(2)O(2)-induced cell death, whereas
      treatment with purified mitogens commonly found in BPE, growth hormone and basic
      fibroblast growth factor, did not protect against oxidative damage. Taken
      together, these data suggest that BPE contains proteins or protein complexes with
      remarkable antioxidant activity. These yet unidentified compounds appear to
      confer protection against H(2)O(2)-induced cell death by tyrosine kinase
      dependent pathways that increase intracellular ROS generation. The antioxidant
      activity of BPE may represent a confounding variable when studying oxidative
      stress in cells maintained in BPE-supplemented serum-free medium.

PMID- 14690453
TI  - Critical cysteine residues for regulation of integrin alphaIIbbeta3 are clustered
      in the epidermal growth factor domains of the beta3 subunit.
AB  - Chemical or enzymic reduction/oxidation of integrin cysteine residues (e.g. by
      reducing agents and protein disulphide isomerase) may be a mechanism for
      regulating integrin function. It has also been proposed that unique cysteine
      residues in the integrin beta3 subunit are involved in the regulation of
      alphaIIbbeta3. In the present study, we studied systematically the role of
      disulphide bonds in beta3 on the ligand-binding function of alphaIIbbeta3 by
      mutating individual cysteine residues of beta3 to serine. We found that the
      disulphide bonds that are critical for alphaIIbbeta3 regulation are clustered
      within the EGF (epidermal growth factor) domains. Interestingly, disrupting only
      a single disulphide bond in the EGF domains was enough to activate alphaIIbbeta3
      fully. In contrast, only two (of 13) disulphide bonds tested outside the EGF
      domains activated alphaIIbbeta3. These results suggest that the disulphide bonds
      in the EGF domains should be intact to keep alphaIIbbeta3 in an inactive state,
      and that there is no unique cysteine residue in the EGF domain critical for
      regulating the receptor. The cysteine residues in the EGF domains are potential
      targets for chemical or enzymic reduction.

PMID- 14690454
TI  - Interferon-gamma inhibits interferon-alpha signalling in hepatic cells: evidence
      for the involvement of STAT1 induction and hyperexpression of STAT1 in chronic
      hepatitis C.
AB  - IFN-gamma (interferon-gamma) modulates IFN-alpha therapy in chronic hepatitis C
      infection; however, the underlying mechanism remains unclear. Here we demonstrate
      that long-term (3-6 days) but not short-term (up to 1 day) IFN-gamma treatment of
      human hepatoma Hep3B cells attenuates IFN-alpha activation of STAT1 (signal
      transducers and activators of transcription factor 1), STAT2 and STAT3, but
      enhances IFN-gamma and interleukin 6 activation of STATs. Prolonged exposure to
      IFN-gamma also significantly induces STAT1 protein expression without affecting
      STAT2, STAT3 and ERK (extracellular-signal-regulated kinase) 1/2 protein
      expression. To determine the role of STAT1 protein overexpression in regulation
      of IFN-alpha signalling, Hep3B cells were stably transfected with wild-type
      STAT1. Overexpression of STAT1 via stable transfection enhances IFN-gamma
      activation of STAT1, but surprisingly attenuates IFN-alpha activation of STAT1,
      STAT2 and STAT3 without affecting Janus kinase activation. This STAT1-mediated
      inhibition does not require STAT1 tyrosine phosphorylation because overexpression
      of dominant-negative STAT1 with a mutation on tyrosine residue 701 also blocks
      IFN-alpha activation of STAT1, STAT2 and STAT3. Moreover, overexpression of STAT1
      blocks IFN-alpha-activated STAT2 translocation from IFN-alpha receptor 2 to IFN
      alpha receptor 1, a critical step in IFN-alpha signalling activation. Finally,
      significantly higher levels of STAT1 protein expression, which is probably
      induced by IFN-gamma, are detected in the majority of hepatitis C virus-infected
      livers compared with healthy controls. In conclusion, long-term IFN-gamma
      treatment inhibits IFN-alpha-activated signals most probably, at least in part,
      through the induction of STAT1 protein expression, which could partly contribute
      to IFN-alpha treatment failure in hepatitis C patients.

PMID- 14690455
TI  - Over-expression of sterol-regulatory-element-binding protein-1c (SREBP1c) in rat
      pancreatic islets induces lipogenesis and decreases glucose-stimulated insulin
      release: modulation by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR).
AB  - Accumulation of intracellular lipid by pancreatic islet beta-cells has been
      proposed to inhibit normal glucose-regulated insulin secretion
      ('glucolipotoxicity'). In the present study, we determine whether over-expression
      in rat islets of the lipogenic transcription factor SREBP1c (sterol-regulatory
      element-binding protein-1c) affects insulin release, and whether changes in islet
      lipid content may be reversed by activation of AMPK (AMP-activated protein
      kinase). Infection with an adenovirus encoding the constitutively active nuclear
      fragment of SREBP1c resulted in expression of the protein in approx. 20% of islet
      cell nuclei, with a preference for beta-cells at the islet periphery. Real-time
      PCR (TaqMan) analysis showed that SREBP1c up-regulated the expression of FAS
      (fatty acid synthase; 6-fold), acetyl-CoA carboxylase-1 (2-fold), as well as
      peroxisomal-proliferator-activated receptor-gamma (7-fold), uncoupling protein-2
      (1.4-fold) and Bcl2 (B-cell lymphocytic-leukaemia proto-oncogene 2; 1.3-fold). By
      contrast, levels of pre-proinsulin, pancreatic duodenal homeobox-1, glucokinase
      and GLUT2 (glucose transporter isoform-2) mRNAs were unaltered. SREBP1c
      transduced islets displayed a 3-fold increase in triacylglycerol content,
      decreased glucose oxidation and ATP levels, and a profound inhibition of glucose
      , but not depolarisation-, induced insulin secretion. Culture of islets with the
      AMPK activator 5-amino-4-imidazolecarboxamide riboside decreased the expression
      of the endogenous SREBP1c and FAS genes, and reversed the effect of over
      expressing active SREBP1c on FAS mRNA levels and cellular triacylglycerol
      content. We conclude that SREBP1c over-expression, even when confined to a subset
      of beta-cells, leads to defective insulin secretion from islets and may
      contribute to some forms of Type II diabetes.

PMID- 14690457
TI  - Melanocytic nevi of the breast: a histologic case-control study.
AB  - BACKGROUND: Melanocytic nevi in the genital, acral, and flexural sites often
      display clinical and histologic features that may simulate melanoma. We verified
      whether this is the case also for nevi of the breast. METHODS: Eleven
      dermatopathologists, from nine Italian Institutions, collected the specimens of
      melanocytic lesions from the breast and other body sites, excluding the acral,
      genital, and flexural areas, as controls. Cases and controls were matched for sex
      and age. All nevi were observed 'blindly' and simultaneously by all participants.
      For each lesion, 10 histological parameters were analyzed: asymmetry, absence of
      lateral demarcation of melanocytes, lentiginous proliferation, nested and
      dyshesive pattern, intraepidermal melanocytes above the basal layer, involvement
      of the hair follicle, absence of maturation of dermal melanocytes, melanocytic
      atypia, fibroplasia of the papillary dermis, and lymphocytic dermal infiltrate.
      Each parameter was scored 2 when present and 1 when absent or not valuable. A
      total score was calculated for each lesion. Results were statistically analyzed
      by the chi-square test and the Mann-Whitney U-test. RESULTS: One hundred and one
      nevi came from the breast area and 97 from elsewhere. Breast nevi exhibited
      significantly more atypical features than nevi from other sites. In particular,
      breast nevi with intraepidermal melanocytes, melanocytic atypia, and dermal
      fibroplasia were significantly more numerous. We did not find any sexual
      difference. CONCLUSIONS: To avoid undue concerns, dermatopathologists should be
      aware that melanocytic nevi of the breast may show a high degree of atypical
      features.

PMID- 14690456
TI  - Pyridoxine biosynthesis in yeast: participation of ribose 5-phosphate ketol
      isomerase.
AB  - To identify the genes involved in pyridoxine synthesis in yeast, auxotrophic
      mutants were prepared. After transformation with a yeast genomic library, a
      transformant (A22t1) was obtained from one of the auxotrophs, A22, which lost the
      pyridoxine auxotrophy. From an analysis of the plasmid harboured in A22t1, the
      RKI1 gene coding for ribose 5-phosphate ketol-isomerase and residing on
      chromosome no. 15 was identified as the responsible gene. This notion was
      confirmed by gene disruption and tetrad analysis on a diploid prepared from the
      wild-type and the auxotroph. The site of mutation on the RKI1 gene was identified
      as position 566 with a transition from guanine to adenine, resulting in amino
      acid substitution of Arg-189 with lysine. The enzymic activity of the Arg189-
      >Lys (R189K) mutant of ribose 5-phosphate ketolisomerase was 0.6% when compared
      with the wild-type enzyme. Loss of the structural integrity of the protein seems
      to be responsible for the greatly diminished activity, which eventually leads to
      a shortage of either ribose 5-phosphate or ribulose 5-phosphate as the starting
      or intermediary material for pyridoxine synthesis.

PMID- 14690458
TI  - A reappraisal of the histologic findings of pigmented pretibial patches of
      diabetes mellitus.
AB  - BACKGROUND: Pigmented pretibial patches (PPPs) are the most common cutaneous
      alterations in diabetes mellitus, found in up to 50% of diabetic patients. They
      classically present as flat-topped, dull-red papules on the pretibial areas,
      later becoming hyperpigmented and atrophic. Little is known regarding the
      pathogenesis of these lesions, and the histopathologic findings have been
      regarded as non-specific. METHODS: We investigated the clinical and pathologic
      attributes of a series of 12 diabetic patients with PPP in an effort to discern
      any specific histologic attributes compared to normal skin removed from diabetic
      patients with cutaneous carcinoma. RESULTS: All cases of PPP showed hyaline
      microangiopathy, all patients showed extravasated erythrocytes and/or hemosiderin
      deposits, and 10 patients showed an appreciable number of perivascular plasma
      cells. The average number of plasma cells per vascular plexus was 2.2. Control
      specimens removed from five diabetic patients showed hyaline microangiopathy, and
      three showed extravasated erythrocytes and hemosiderin. One patient showed a
      single vascular plexus with two plasma cells, p = 0.01. CONCLUSION: The presence
      of increased dermal perivascular plasma cells in the appropriate clinical context
      might be an important and under-recognized clue for PPP. The pathogenic
      significance of this finding is unknown.

PMID- 14690459
TI  - The diagnostic utility of p63, CK5/6, CK 7, and CK 20 in distinguishing primary
      cutaneous adnexal neoplasms from metastatic carcinomas.
AB  - BACKGROUND: Distinguishing primary cutaneous adnexal neoplasms (PCANs) from
      metastatic carcinomas (MCs) can be difficult. We study the utility of p63, CK
      5/6, CK 7, and 20 expression in PCAN vs. MC. METHODS: Twenty-one PCAN with sweat
      gland differentiation (six benign, 15 malignant), one sebaceous carcinoma, and 15
      MC (14 adenocarcinomas, one urothelial carcinoma) to skin were retrieved from the
      pathology files. Immunostains for p63, CK 5/6, CK 7, and CK 20 were performed and
      graded as follows: 1, <10; 2, 11-50; and 3 >50% of tumor cells stained. RESULTS:
      Twenty of 22 PCAN expressed p63 and CK 5/6. Four of 15 and two of 15 MC were
      positive for CK 5/6 and p63, respectively. Thirteen of 22 PCAN and 13 of 15 MC
      were positive for CK 7, respectively. All PCAN were negative for CK 20, two of 15
      MC were positive. The sensitivity and specificity for the diagnosis of PCAN were
      91 and 73% for CK 5/6, 91 and 100% for p63, and 60 and 13% for CK 7,
      respectively. CONCLUSIONS: For distinguishing PCAN from MC: (1) positivity for
      p63 and CK 5/6 are relatively specific and sensitive for PCAN, (2) CK 7 and 20
      are neither sensitive nor specific, and (3) CK 7 positivity in PCAN was focal
      with a specific pattern in contrast to the diffuse positivity for MC.

PMID- 14690460
TI  - Cellular nodules in congenital pattern nevi.
AB  - BACKGROUND: The diagnosis of 'cellular dermal nodule in melanocytic nevi' is
      challenging, as it can simulate invasive and tumorigenic melanoma. Because
      cellular nodules are presumed benign, it is essential to differentiate them from
      true malignant melanoma arising within a nevus, which portends a poor prognosis.
      Although presumed benign, to date, no published long-term follow-up studies have
      proved the benignity of this lesion. METHODS: To better understand the clinical
      behavior and histological features of these lesions, we present a clinical
      pathological study of a cohort of 26 cases, for which we obtained clinical follow
      up by chart review and questionnaires. RESULTS: Clinical follow up was obtained
      on 16 out of 26 patients (61.5%) and ranged from 12 to 132 months (average 62.3
      months). The cellular nodules in congenital pattern nevi, reported here, had an
      invariably benign clinical course. CONCLUSIONS: Features useful in
      differentiating cellular nodule from melanoma include: (1) lack of high-grade
      uniform cellular atypia; (2) lack of necrosis within the nodule; (3) rarity of
      mitoses; (4) evidence of maturation in the form of blending or transitional forms
      between the cells in the nodule and the adjacent nevus cells; (5) lack of
      pagetoid spread into the overlying epidermis; and (6) no destructive expansile
      growth. The difference between cellular nodule and melanoma arising from nevus
      can be very subtle, and it is important to emphasize that these lesions must be
      assessed on an individual case-by-case basis.

PMID- 14690461
TI  - The histologic spectrum of cutaneous sarcoidosis: a study of twenty-eight cases.
AB  - BACKGROUND: Naked sarcoidal granulomas (NSGs) are the characteristic histologic
      finding in sarcoidosis. This descriptive study was designed to identify the
      frequency of other histologic changes in cutaneous sarcoidosis. METHODS: The
      slides from 28 sequential biopsies previously diagnosed as sarcoidosis in
      patients with known systemic sarcoidosis were reviewed. RESULTS: Classic NSGs
      were identified in 25 biopsies (89%). Four biopsies contained tuberculoid
      granulomas, two with neutrophils suggesting infection (cultures negative). Five
      biopsies contained interstitial granulomas that resembled granuloma annulare and
      necrobiosis lipoidica in one case each. Additional histologic findings included
      birefringent foreign material in 14 biopsies (50%), focal necrosis (43%),
      elastophagocytosis (39%), linear peri-neural granulomas resembling leprosy (25%),
      increased dermal mucin (18%) and lichenoid inflammation (14%) [two with plasma
      cells resembling syphilis (7%)]. In all but three cases, the clinical morphology
      of the lesions suggested sarcoidosis. Special stains for mycobacteria and fungi
      were negative. CONCLUSIONS: The histologic changes in cutaneous sarcoidosis are
      more diverse than previously recognized. In sarcoidosis, foreign material may be
      a frequent nidus for cutaneous granuloma formation. Histologic examination
      without the clinical history could lead to a misdiagnosis of leprosy, syphilis,
      other infectious granulomas, rosacea, granuloma annulare, necrobiosis lipoidica,
      and foreign body reaction in selected cases from this series.

PMID- 14690462
TI  - Immunolabeling pattern of syndecan-1 expression may distinguish pagetoid Bowen's
      disease, extramammary Paget's disease, and pagetoid malignant melanoma in situ.
AB  - The differential diagnosis of pagetoid cells within the epidermis rests primarily
      between pagetoid Bowen's disease (PBD), extramammary Paget's disease (EPD), and
      pagetoid malignant melanoma (MIS) in situ. Although morphologic clues are often
      helpful in differentiating these lesions, the use of immunohistochemistry is
      often necessary to arrive at the correct diagnosis. Syndecan-1 is a cell-surface
      proteoglycan that mediates adhesion between cells and the extracellular matrix,
      and between cells themselves. Twenty-two cases of PBD, four cases of
      intraepidermal EPD, and 13 cases of MIS were examined for syndecan-1
      immunoreactivity. Cell-membrane syndecan-1 immunoreactivity was evident in PBD,
      cytoplasmic syndecan-1 immunoreactivity was evident in EPD, whereas
      immunoreactivity for syndecan-1 was not present in MIS. The patterns of syndecan
      1 immunoreactivity in these lesions may be a useful adjunct in the
      differentiation of PBD, EPD, and MIS.

PMID- 14690463
TI  - Giant basal cell carcinoma associated with human papillomaviruses infection.
AB  - Different criteria have been used to define giant basal cell carcinoma (BCC).
      However, the majority of tumors of 10 cm or greater in diameter have a
      characteristic clinical and histopathologic presentation. As a group, these
      tumors often show metastatic spread as opposed to all other BCCs that rarely
      metastasize. We present an additional patient with a giant BCC greater than 100
      cm2. This tumor had a characteristic location and infiltrative growth pattern.
      Unusual features of this tumor included a lack of expression of BCL-2 with a
      greater proportion of cycling tumor cells expressing proliferation markers than
      conventional BCC, as well as expression of anogenital human papillomaviruses
      (HPV) subtypes with oncogenic potential. The association of HPV with BCCs has
      rarely been studied and may not be identical to HPV-induced genital squamous cell
      carcinomas. However, the findings in this patient suggest that HPV may play a
      role in the development of some chronic giant BCCs.

PMID- 14690464
TI  - Lichenoid graft vs. host disease following liver transplantation.
AB  - BACKGROUND: Graft vs. host disease (GVHD) is a common complication of bone marrow
      transplantation (BMT) but is rarely seen after solid organ transplantation.
      METHODS: We report a case of lichenoid GVDH arising in a 60-year-old man 10 weeks
      after orthotopic liver transplantation. RESULTS: Skin biopsies revealed changes
      suggestive of lichenoid GVHD, but histological features differed from those
      described in post bone marrow (stem cell) transplant GVHD, in that a dense
      lymphoid infiltrate was present. The brisk infiltrate contained eosinophils that
      initially led to concern for a lichenoid drug eruption. The patient developed
      multiorgan GVHD after reduction in immunosuppression. The diagnosis of chronic
      GVHD was confirmed by the demonstration of chimerism in the patient's peripheral
      blood. The generalized cutaneous eruption and systemic manifestations responded
      to salvage therapy including intravenous immunoglobulin infusion, increased
      immunosuppression with high-dose steroids, mycophenolate mofetil, and systemic
      and topical tacrolimus. CONCLUSIONS: In interpreting skin biopsies, it is
      important to recognize that brisk inflammation may be seen in GVHD in the setting
      of solid organ transplantation, in contrast to the more sparse inflammation
      typical of GVHD following BMT. The clinical and histologic differential diagnosis
      included the eruption of lymphocyte recovery, drug reaction, and viral exanthem.
      We provide a conceptual framework for evaluating generalized cutaneous changes
      that may occur post transplantation.

PMID- 14690465
TI  - Eruptive multiple blue nevi of the penis: a clinical dermoscopic pathologic case
      study.
AB  - Multiple blue nevi have rarely been reported, and the majority of the lesions are
      located on the trunk and lower extremities. The blue nevus is a rare lesion on
      genital mucosa and may cause confusion in differential diagnosis with other
      pigmented lesions such as genital melanocytic macules, lentigo simplex, and
      malignant melanoma. Here, we describe an unusual patient who presented with a
      sudden onset in adulthood of multiple blue nevi on the glans penis. The
      epiluminescence examination revealed a substantially homogenous bluish
      pigmentation, which led us to favor a diagnosis of blue nevus, whereas not
      entirely excluding the possibility of a regressing melanoma or a metastatic
      melanoma. Because of the well-known diagnostic value of the blue hue in the
      diagnosis of malignancy by dermoscopy, a careful examination of these lesions
      should be made in order to minimize any risk of misclassification with melanoma.

PMID- 14690466
TI  - Photo-distributed neutrophilic drug eruption and adult respiratory distress
      syndrome associated with antidepressant therapy.
AB  - Drug reactions are well-known complications of antidepressant therapy, often
      related to photosensitization. Herein is reported a singular case of
      antidepressant (amoxapine and citalopram) and anxiolytic related (perphenazine)
      photo-distributed neutrophilic dermatosis and adult respiratory distress syndrome
      (ARDS). The clinicopathologic findings displayed overlapping features with drug
      induced Sweet's syndrome, acute generalized exanthematous pustulosis (AGEP), and
      so-called sterile neutrophilic folliculitis with perifollicular vasculopathy. Of
      the three medications, only amoxapine has been associated with AGEP. Treatment
      with high-dose systemic corticosteroids and cessation of drug therapy was
      followed by rapid resolution of the cutaneous eruption and respiratory distress.
      The possibility that neutrophil infiltration of the lung and/or accumulation of
      neutrophils in the skin and blood served as a source for reactive oxygen species,
      leading to lung injury and subsequent ARDS, is discussed.

PMID- 14690467
TI  - Benign ectopic thyroid tissue in a cutaneous location: a case report and review.
AB  - BACKGROUND: For many years, lateral, aberrant thyroid tissue in adults was a term
      used almost exclusively for metastatic thyroid carcinoma. However, aberrant,
      benign ectopic thyroid tissue does occur, and it is most commonly found as a part
      of the evaluation of endocrine dysfunction. Rarely, aberrant, benign ectopic
      thyroid presents as a primary mass. CASE REPORT: We present a 35-year-old female
      who presented for removal of a lifelong posterior lateral neck nodule. RESULTS:
      Histologic examination and immunohistochemical studies confirmed the presence of
      aberrant, benign ectopic thyroid tissue. The patient had no endocrine problems,
      and she had a normally located and functioning thyroid gland. CONCLUSIONS: This
      case illustrates that not all aberrant thyroid tissues in adults are malignant or
      associated with endocrine disorders. This case also illustrates the rare
      association of ectopic thyroid and a normally located and functioning thyroid
      gland. In this patient, a somatic mutation in a transcription factor important in
      thyroid migration could explain these findings.

PMID- 14690468
TI  - Verrucous carcinoma of the axilla: case report and review.
AB  - BACKGROUND: Verrucous carcinoma, a variant of squamous cell carcinoma, is
      distinct from squamous cell carcinoma in morphology and behavior. It
      preferentially occurs on the oropharyngeal mucosa, the urogenital mucosa, and the
      soles. In contrast to its malignant clinical picture, the tumor grows locally
      invasive but is histologically benign and metastasizes rarely. METHODS: We report
      the uncommon occurrence of a large verrucous carcinoma on apparently uninvolved
      skin in the right axilla in a 47-year-old male. RESULTS: Histologic examination
      reveals a cauliflower-like tumor consisting of deep invaginated epidermal
      proliferation with rabbit burrow-like, keratin-filled sinus formations; the
      basement membrane, however, remains intact. Immunohistology showed positivity for
      pancytokeratin (KL-1) and cytokeratin (CK) 18 and negativity for CK7, and
      assessment of the proliferative activity of the tumor cells revealed low
      percentage of Ki-67 expression. Furthermore, there were only scattered cells
      expressing p53 or bcl-2. Polymerase chain reaction excluded the presence of human
      papillomavirus. After complete excision, no signs of recurrence occurred over a
      follow-up period of three years. CONCLUSION: Verrucous carcinoma should be
      distinguished from typical squamous cell carcinoma. The clinicopathological
      features, differential diagnosis, and therapy are discussed here together with
      the molecular biologic aspects of the tumor.

PMID- 14690469
TI  - Tumefactive lipedema with pseudoxanthoma elasticum-like microscopic changes.
AB  - BACKGROUND: Lipedema is a condition characterized by diffuse, bilaterally
      symmetrical, painful swelling of the legs and buttocks. Microscopically, there
      are dermal and septal edema, adipocyte degeneration, and numerous mast cells,
      features held in common with lipedematous alopecia. CASE REPORT: We present the
      case of a 60-year-old woman with a long history of bilateral leg masses with
      microscopic features of lipedema. In addition, elastic-fiber changes typical of
      pseudoxanthoma elasticum (PXE) were discovered within the subcutaneous septa in
      three separate specimens obtained from an affected extremity. The patient did not
      have other clinical findings of PXE, although there was a history of both
      hypertension and congestive heart failure. CONCLUSION: This tumefactive
      presentation of lipedema has not been previously described. Regarding the elastic
      tissue abnormalities, the patient could have either a subclinical form of PXE,
      perhaps predisposing to lipedema, or secondary elastic-tissue changes resulting
      from the massive edema. If the latter is the case, then this could represent an
      unusual manifestation of localized acquired cutaneous PXE (calcific elastosis).

PMID- 14690470
TI  - Alopecia mucinosa or follicular mucinosis - the problem is terminology!

PMID- 14690473
TI  - Strategies for identifying genes that play a role in spinal cord regeneration.
AB  - A search for genes that promote or block CNS regeneration requires numerous
      approaches; for example, tests can be made on individual candidate molecules.
      Here, however, we describe methods for comprehensive identification of genes up-
      and down-regulated in neurons that can and cannot regenerate after injury. One
      problem concerns identification of low-abundance genes out of the 30,000 or so
      genes expressed by neurons. Another difficulty is knowing whether a single gene
      or multiple genes are necessary. When microchips and subtractive differential
      display are used to identify genes turned on or off, the numbers are still too
      great to test which molecules are actually important for regeneration. Candidates
      are genes coding for trophic, inhibitory, receptor and extracellular matrix
      molecules, as well as unknown genes. A preparation useful for narrowing the
      search is the neonatal opossum. The spinal cord and optic nerve can regenerate
      after injury at 9 days but cannot at 12 days after birth. This narrow window
      allows genes responsible for the turning off of regeneration to be identified. As
      a next step, sites at which they are expressed (forebrain, midbrain, spinal cord,
      neurons or glia, intracellular or extracellular) must be determined. An essential
      step is to characterize proteins, their levels of expression, and their
      importance for regeneration. Comprehensive searches for molecular mechanisms
      represent a lengthy series of experiments that could help in devising strategies
      for repairing injured spinal cord.

PMID- 14690474
TI  - Identifying genes for neuron survival and axon outgrowth in Hirudo medicinalis.
AB  - We have studied the molecular basis of nervous system repair in invertebrate
      (Hirudo medicinalis) nerve cells. Unlike in mammals, neurons in invertebrates
      survive injury and regrow processes to restore the connections that they held
      before the damage occurred. To identify genes whose expression is regulated after
      injury, we have used subtractive probes, constructed from regenerating and non
      regenerating ganglia from the leech Hirudo medicinalis, to screen cDNA libraries
      made from whole leech CNS or from identified microdissected neurons. We have
      identified genes of known or predicted function as well as novel genes. Known
      genes up-regulated within hours of injury and that are widely expressed in
      invertebrate and mammalian cells include thioredoxin and tubulin. Other known
      genes, e.g. Cysteine Rich Intestinal Protein (CRIP), have previously been
      identified in mammalian cells though not in regenerating adult neurons. Two
      regulated genes identified, myohemerythrin and the novel protein ReN3 are
      exclusively expressed in invertebrates. Thus our approach has enabled us to
      identify genes, present in a neuron of known function, that are up- and down
      regulated within hours of axotomy, and that may underpin the intrinsic ability of
      invertebrate neurons to survive damage and initiate regrowth programmes.

PMID- 14690475
TI  - Factors secreted by Schwann cells stimulate the regeneration of neonatal retinal
      ganglion cells.
AB  - The adult mammalian central nervous system (CNS) does not repair after injury.
      However, we and others have shown in earlier work that the neonatal CNS is
      capable of repair and importantly of allowing regenerating axons to re-navigate
      through the same pathways as they did during development. This phase of neonatal
      repair is restricted by the fragility of neurons after injury and a lack of
      trophic factors that enable their survival. Our aim is to define better the
      factors that sustain neurons after injury and allow regeneration to occur. We
      describe some of our work using Schwann cells to promote the regeneration of
      neurons from young postnatal rodents. We have established rapid methods for
      purifying Schwann cells without the use of either anti-mitotic agents to suppress
      contaminating fibroblasts or mitotic stimulation to generate large numbers of
      Schwann cells. The rapidly purified Schwann cells have been used to generate
      conditioned medium that we have shown stimulates axon regeneration in cultured
      retinal ganglion cell neurons. We also show that the positive effects of Schwann
      cells are still present after pharmacological blockade of the neurotrophin
      receptors, suggesting that novel factors mediate these effects.

PMID- 14690477
TI  - A role for cAMP in regeneration of the adult mammalian CNS.
AB  - Injury to the adult mammalian central nervous system (CNS) often results in
      permanent loss of sensory and motor function. This is due to the failure of
      injured axons to regenerate. The inhibitory nature of the CNS can be attributed
      to several factors, including formation of the glial scar, the presence of
      several molecules, associated with myelin, which inhibit axonal regrowth, and the
      intrinsic growth state of these neurons. Encouraging regeneration in the adult
      mammalian CNS therefore will require targeting one or all of these factors
      following injury. Here we illustrate recent work from our laboratory that
      identifies some of the signalling components involved in modulation of the
      intrinsic growth state of adult neurons. When activated, these signalling
      pathways can induce axonal regeneration in the presence of the myelin-associated
      inhibitors both in vitro and in vivo.

PMID- 14690478
TI  - Olfactory ensheathing cells (OECs) and the treatment of CNS injury: advantages
      and possible caveats.
AB  - One of the main research strategies to improve treatment for spinal cord injury
      involves the use of cell transplantation. This review looks at the advantages and
      possible caveats of using glial cells from the olfactory system in transplant
      mediated repair. These glial cells, termed olfactory ensheathing cells (OECs),
      ensheath the axons of the olfactory receptor neurons. The primary olfactory
      system is an unusual tissue in that it can support neurogenesis throughout life.
      In addition, newly generated olfactory receptor neurons are able to grow into the
      CNS environment of the olfactory bulb tissue and reform synapses. It is thought
      that this unique regenerative property depends in part on the presence of OECs.
      OECs share some of the properties of both astrocytes and Schwann cells but appear
      to have advantages over these and other glial cells for CNS repair. In
      particular, OECs are less likely to induce hypertrophy of CNS astrocytes. As well
      as remyelinating demyelinated axons, OEC grafts appear to promote the restoration
      of functions lost following a spinal cord lesion. However, much of the evidence
      for this is based on behavioural tests, and the mechanisms that underlie their
      potential benefits in transplant-mediated repair remain to be clarified.

PMID- 14690476
TI  - Chondroitin sulphate proteoglycans: preventing plasticity or protecting the CNS?
AB  - It is well established that axonal regeneration in the adult CNS is largely
      unsuccessful. Numerous axon-inhibitory molecules are now known to be present in
      the injured CNS, and various strategies for overcoming these obstacles and
      enhancing CNS regeneration have been experimentally developed. Recently, the use
      of chondroitinase-ABC to treat models of CNS injury in vivo has proven to be
      highly beneficial towards regenerating axons, by degrading the axon-inhibitory
      chondroitin sulphate glycosaminoglycan chains found on many proteoglycans in the
      astroglial scar. This enzyme has now been shown to restore synaptic plasticity in
      the visual cortex of adult rats by disrupting perineuronal nets, which contain
      high levels of chondroitin sulphate proteoglycans (CS-PGs) and are expressed
      postnatally around groups of certain neurons in the normal CNS. The findings
      suggest exciting prospects for enhancing growth and plasticity in the adult CNS;
      however, some protective roles of CS-PGs in the CNS have also been demonstrated.
      Clearly many questions concerning the mechanisms regulating expression of
      extracellular matrix molecules in CNS pathology remain to be answered.

PMID- 14690479
TI  - Application of differential display, with in situ hybridization verification, to
      microscopic samples of breast cancer tissue.
AB  - The technique of differential display (DD) has been used widely to identify
      potentially interesting overexpressed or repressed genes in a variety of compared
      samples. When used in studying tissue samples, it inevitably confronts problems
      of limited amount of input material and cell-type heterogeneity. We report here
      the application of in situ hybridization as a method of confirmatory test for DD
      as well as definition of cell type expressing differential cDNA. This procedure
      employed material derived from a single case of human mammary, grade III,
      infiltrating ductal carcinoma, using free-hand microdissection, where we have
      compared gene expression profiles in invasive tumour with those in adjacent
      normal tissue. A total of 21 cDNAs were found to be differentially expressed
      between the two tissue types; 11 upregulated in the tumour sample and 10
      upregulated in the normal sample. Six cDNAs were utilized as probes for in situ
      hybridization analysis of a further five cases of comparably staged breast
      cancer. One of these clones, 11AT1, which was found to be homologous to Hsc70,
      was shown to be overexpressed in tumour cells relative to adjacent normal stroma
      and to benign glandular epithelium in all five cases; an increase in expression
      was further confirmed at protein level by immunohistochemistry. The study
      demonstrated the applicability of in situ hybridization as a screening test in DD
      strategy for studying tissue material and a reasonable technique combination of
      identifying changes in gene expression associated with tumour development.

PMID- 14690480
TI  - Roles of inducible nitric oxide synthase in the development and healing of
      experimentally induced gastric ulcers.
AB  - The roles of inducible nitric oxide synthase (iNOS) in the development and
      healing of gastric ulcers have not been fully characterized. We characterized
      iNOS expression in experimentally induced ulcers in rat and mouse stomachs and
      investigated the roles of iNOS using iNOS gene-deficient (iNOS-/-) mice and
      wildtype mice. Gastric ulcers were induced in rats and mice by the application of
      acetic acid and cryoinjury, respectively. iNOS expression was detected on days 1
      7 and peaked 3 days after ulcer induction in the rat. iNOS-positive cells were
      distributed mainly among the infiltrating cells and fibroblasts in the ulcer bed.
      The almost similar courses of healing and iNOS expression were observed in the
      ulcers of mice. During the course of healing, the iNOS gene status did not affect
      cell proliferation in the healing zone or vessel formation in the ulcer bed. iNOS
      deficiency, however, caused larger ulcers and severer inflammation during ulcer
      healing; the clearance of inflammatory cells in the ulcer bed by apoptosis was
      also delayed when the ulcer was re-epithelialized in the iNOS-deficient mice.
      These results indicate that iNOS is expressed in the ulcer bed and that iNOS
      activity may play beneficial roles in the ulcer repair process, possibly by
      regulating inflammation.

PMID- 14690481
TI  - The endothelin-1 receptor antagonists ameliorate histology and ultrastructural
      alterations in the pancreas and decrease trypsinogen activation in severe
      taurocholate pancreatitis in rats.
AB  - The role of potent vasoconstrictor endothelin-1 (ET-1) in acute pancreatitis (AP)
      remains controversial. The aim was to compare the effect of nonselective ET RA/B
      (LU-302872) and selective ET RA (LU-302146) antagonists on pancreatic histology,
      ultrastructure and trypsinogen activation in severe taurocholate AP in rats. Male
      Wistar rats with AP were treated with an intraperitoneous injection of 1, 5 and
      10 mg/kg of body weight of each antagonist at 0, 6, 12 and 18 h after
      taurocholate administration. After 24 h, the samples of pancreases were taken for
      histological and ultrastructural examinations and for assessment of trypsinogen
      activation. Both antagonists, at all investigated doses, decreased the damage to
      the acinar cells detected in the light microscope and ultrastructurally.
      Trypsinogen activation increased to 29.7 +/- 3.9% in the AP untreated in
      comparison to the control group [12.7 +/- 1.4% (P<0.001)]. This increase was
      attenuated to 13.8 +/- 2.2% in AP treated with a high dose of the nonselective
      antagonist and to 8.4 +/- 1.7% with low dose of selective antagonist. The
      obtained results indicate that ET-1 could participate in the damage to the
      pancreas during AP. Both antagonists of ET-1 receptors exerted a similar
      beneficial effect on the morphological changes of the pancreas in AP. One of the
      probable mechanism could be the attenuation of trypsinogen activation.

PMID- 14690482
TI  - The effects of lectins on indomethacin-induced small intestinal ulceration.
AB  - Growth factors, such as epidermal growth factor and keratinocyte growth factor,
      have considerable therapeutic potential for repairing mucosal injury in the
      intestine when given systemically. Recently, several lectins have been shown to
      have trophic effects on the intestine when given orally. We examined the effects
      of phytohaemagglutinin (PHA) and concanavalin A (Con-A) on indomethacin-induced
      intestinal injury in rat. Five-week-old rats were randomized to four groups
      (n=5), and intestinal injury was induced by indomethacin injection in three of
      these groups. Elemental diet (ED) feeding was then commenced. The groups were
      thus ED feeding/indomethacin untreated (control group), ED feeding/indomethacin
      treated (ED group), 0.1% PHA-supplemented ED feeding/indomethacin treated (PHA
      group) and 0.1% Con-A-supplemented ED feeding/indomethacin treated (Con-A group).
      After 7 days of feeding, macroscopic inflammatory scores, mucosal permeability,
      myeloperoxidase (MPO) activities and cell proliferation were determined.
      Macroscopic inflammatory scores, mucosal permeability and MPO activities were
      significantly lower in both lectin groups than that in control group. Twenty-four
      hour excretion rate of phenolsulphonphthalein was significantly lower in both
      lectin groups than that in ED group. Cell proliferation of the small intestine
      was significantly increased by both lectins. Lectin supplementation can induce
      ulcer healing following indomethacin-induced damage.

PMID- 14690483
TI  - Extracellular matrix: from structure to function. Proceedings and abstracts of
      the BSMB Spring 2003 Meeting. Oxford, United Kingdom. March 31-April 1, 2003.

PMID- 14690484
TI  - Lifelong premature ejaculation: from authority-based to evidence-based medicine.
AB  - Historically, four periods can be distinguished in the approach to and treatment
      of lifelong premature ejaculation. Although drug treatment has been an option for
      many decades, psychotherapy prevailed as the first choice of treatment. However,
      the application of the principles of evidence-based medicine shows that there is
      little evidence to support the psychological approach and behavioural treatment.
      In contrast, controlled trials with selective serotonin reuptake inhibitors,
      clomipramine and anaesthetic ointments have repeatedly shown the efficacy of both
      daily and 'as-needed' drug treatment to delay ejaculation. Currently, an evidence
      based approach is gradually replacing the authority-based psychological attitude
      that characterized the view of premature ejaculation. Based on
      psychopharmacological studies there is evidence that premature ejaculation is
      related to a diminished serotonergic neurotransmission, and 5-HT2C or 5-HT1A
      receptor disturbances. Moreover, animal studies show the presence of a distinct
      ejaculation-related neural circuit in the central nervous system; its role in
      premature ejaculation remains to be elucidated.

PMID- 14690485
TI  - The management of Peyronie's disease.
AB  - Peyronie's disease has no known cause; recent understanding of the molecular
      mechanisms involved and the development of an animal model will aid the medical
      management of early disease. The medical management of chronic disease is futile
      as the delicate tunical architecture cannot regenerate. Surgical correction of
      the penile deformity is required in a minority of patients, and a choice lies
      between a Nesbit operation and a plaque incision and venous patch in patients who
      are concerned with penile shortening.

PMID- 14690486
TI  - Squamous cell carcinoma of the bladder: pathology, diagnosis and treatment.
AB  - Squamous cell carcinoma (SCC) can occur in both nonbilharzial and bilharzial
      bladders; the two subtypes differ in epidemiology, pathogenesis and
      clinicopathological features. The nonbilharzial type occurs in Western countries
      and represents < 5% of all vesical tumours; it occurs most often in the seventh
      decade with a slight male predominance. The principal predisposing factor is
      prolonged indwelling urethral catheterization in patients with spinal cord injury
      and the main symptom is haematuria. Patients are usually diagnosed at an advanced
      stage and most of the tumours are of moderate and high grades. At cystoscopy
      tumours are predominantly ulcerative and commonly involve the trigone and lateral
      walls. Although distant metastasis is infrequent (8-10%) the prognosis is grave
      and most patients die after failure of locoregional control; radical cystectomy
      provides the best therapy. To avoid nonbilharzial SCC, patients with spinal cord
      injury should be free of catheterization if possible. The outcome can be improved
      by early detection with frequent cytology, cystoscopy and biopsy. Bilharzial SCC
      occurs commonly in the Middle East, South-east Asia and South America where
      schistosomiasis is endemic. In an Egyptian series SCC represented 59% of 1026
      cystectomy specimens. The tumour is diagnosed in the fifth decade, and five times
      more common in men than women. Bladder carcinogenesis is probably related to
      bacterial and viral infections, commonly associated with bilharzial infestation
      rather than the parasite itself. The presentation is often with irritative
      bladder symptoms and haematuria, and many patients present at an advanced stage,
      although most tumours are of low and moderate grades. At cystoscopy tumours are
      predominantly nodular and usually arise from the upper vesical hemisphere. Lymph
      node metastasis occurs in approximately 19% and significantly decreases survival;
      radical cystectomy remains the main treatment, giving a 5-year survival rate of
      50%. Early detection improves the therapeutic yield and prevention is possible by
      combining snail control and mass therapy of the infested rural population by oral
      antibilharzial drugs.

PMID- 14690487
TI  - Laparoscopic treatment of adrenal diseases: 10 years on.
AB  - Since it was initially described in 1992 laparoscopic adrenalectomy (LA) has been
      gaining popularity amongst urologists and its range of applications has
      progressively widened. Ten years after the first report of LA this type of
      operation is presently considered to be the 'standard of care' for most adrenal
      diseases requiring surgery. We define the current role of laparoscopy in the
      management of surgical adrenal diseases, using a Medline search (1997-2002) to
      assess reports of LA, focusing on indications, approaches (transperitoneal and
      retroperitoneoscopic) and comparative analyses, taking particular care to
      evaluate operative duration, rate of conversion and transfusion, complications
      and hospital stay. With both approaches LA is safe and effective and, when
      compared with open surgery, offers the same functional results with all the
      advantages of minimally invasive surgery. We conclude that LA based on either
      approach should be considered the treatment of choice for benign adrenal lesions.
      Although very promising, conservative surgery and LA should still be evaluated in
      cases of malignancy.

PMID- 14690489
TI  - The enhanced spontaneous activity of the diabetic colon is not the consequence of
      impaired inhibitory control mechanisms.
AB  - 1. Approximately 45% of patients with diabetes mellitus have gastrointestinal
      complications such as diarrhoea and constipation, but the underlying aetiology is
      unclear. The present study investigates alterations in spontaneous motility of
      the colon that may be, in part, responsible for these symptoms using an
      established animal model of diabetes. 2. Rats were rendered diabetic by a single
      intraperitoneal injection of streptozotocin and age-matched controls were
      injected with citrate buffer. Rats were sacrificed after 8-weeks and proximal
      colonic circular muscle tissue mounted in organ baths. 3. Spontaneous activity
      was observed in both control and diabetic tissues, but this activity was almost
      doubled in colonic tissue taken from diabetic rats. It was hypothesized that this
      increase was due to a deficit in inhibitory control of the colon in the diabetic
      state. 4. Possible alterations in nitrergic and vasoactive intestinal polypeptide
      (VIP)ergic control were investigated using a range of pharmacological tools. 5.
      Sodium nitroprusside, VIP and antioxidants (reduced glutathione, ascorbate and
      alpha-tocopherol) inhibited the spontaneous activity, but the level of inhibition
      observed was not different in diabetic tissue compared with control. 6. Arginine,
      [D-p-Cl-Phe6, Leu17]-VIP and alpha-chymotrypsin had no effect on spontaneous
      activity in either sets of tissue. 7. N omega-nitro-L-arginine produced a small,
      but significant, increase in the level of spontaneous activity, but the degree of
      increase was not different between control and diabetic tissues. 8. Western blots
      demonstrated that there was no inducible-nitric oxide synthase (iNOS) in control
      or diabetic tissues and that the levels of endothelial-NOS (eNOS) and neuronal
      NOS (nNOS) detected were not statistically significantly different. The [3H]
      citrulline assay established that the functionality of the NOS isoforms present
      were unaltered in the diabetic state. 9. This study demonstrates that there is a
      marked alteration in motility in the colon taken from diabetic animals. However,
      the change in motility is unlikely to be due to a change in inhibitory control
      mechanisms and may be due to an increased excitability.

PMID- 14690490
TI  - NO/cyclic GMP pathway mediates the relaxation of feline lower oesophageal
      sphincter.
AB  - 1. We examined the role of the NO/cyclic GMP (cyclic GMP) pathway in nitric oxide
      (NO)- and vasoactive intestinal peptide (VIP)-induced relaxation of feline lower
      oesophageal sphincter (LES). Furthermore, it was studied whether methylene blue,
      LY83583 and ODQ, which are soluble guanylate cyclase (sGC) inhibitors, could
      inhibit NO-induced relaxation. 2. The nitric oxide synthase (NOS) inhibitor, N
      omega-nitro-L-arginine (L-NNA) had no effect in sodium nitropruside (SNP)-induced
      relaxation, but 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1)-induced
      relaxation was decreased by the pretreatment of L-NNA, which showed that SIN-1,
      not SNP, could activate NOS to cause relaxation. Methylene blue and LY83583 did
      not inhibit the relaxation by SNP and SIN-1. However, the more specific sGC
      inhibitor ODQ blocked the relaxation induced by NO donors. 3. To identify the
      relationship of NOS, sGC and adenylate cyclase in VIP-induced relaxation, tissue
      were pretreated with L-NNA and ODQ and SQ22536. These inhibitors produced
      significant inhibition of this response to VIP. The adenylyl cyclase inhibitor SQ
      22536 also inhibited relaxation by VIP. 4. In conclusion, our data showed that
      SNP- and SIN-1-induced relaxation was mediated by sGC. Of sGC inhibitors,
      methylene blue and LY83583 were not adequate for the examination of NO donor
      induced feline LES smooth muscle relaxation. VIP also caused relaxation by the
      pathway involving NO and cGMP and cAMP.

PMID- 14690491
TI  - Opposite effects of endogenous nitric oxide and prostaglandin F2 alpha in the rat
      mesenteric bed.
AB  - 1. The relationship between the effects of endogenous nitric oxide (NO) and
      prostanoids on the noradrenaline (NA)-induced contractions and the mechanisms
      involved were investigated in the rat perfused mesenteric bed, using NG-nitro-L
      arginine methyl ester (l-NAME), a NO synthase inhibitor and sodium nitroprusside
      (SNP), a NO donor. 2. The constrictor responses to NA were reduced to 50% by the
      cyclooxygenase inhibitor 10 microm indomethacin as well as by 1 microM SNP. When
      indomethacin and SNP were perfused simultaneously the contractions were further
      reduced. 3. The NA-induced contractions were increased by the addition of 400
      microM L-NAME and the addition of either indomethacin or SNP abolished such
      increases. The simultaneous perfusion of both agents further reduced the
      contractions. 4. Removal of the endothelium increased NA-induced contractions to
      a similar extent as L-NAME and this increase was abolished by indomethacin as
      well as by SNP. 5. The perfusion of 10 microM NA augmented the release of
      prostaglandin (PG) F2 alpha by the mesenteric bed without modifications in any
      other prostanoid. In the presence of L-NAME, this effect was further increased.
      However, SNP abolished the NA-induced stimulation of PGF2 alpha release. 6. In de
      endothelialized preparations NA also stimulated PGF2 alpha production as observed
      in intact preparations. This effect was more marked in the presence of L-NAME; in
      contrast, SNP abolished the stimulation. 7. In conclusion, the present results
      suggest an opposite action between NO and PGF2 alpha on the NA-induced
      contractions in the rat mesenteric bed.

PMID- 14690492
TI  - Effect of cardiac vagal outflow on complexity and fractal correlation properties
      of heart rate dynamics.
AB  - 1. Cardiac vagal outflow is the major factor determining the magnitude of heart
      rate (HR) variability analysed by traditional time and frequency domain methods.
      New analysis techniques, such as fractal and complexity methods, have been
      developed to probe non-linear features in HR behaviour that may not be detectable
      by traditional methods. 2. We investigated the effects of vagal blockade
      (glycopyrrolate i.v. 5 microg kg-1 h-1 for 2 h, n = 8 vs. unmedicated control
      group, n = 8) and various breathing patterns (n = 12) on two non-linear measures
      of HR variability--detrended fluctuation analysis (DFA) and approximate entropy
      (ApEn)--in healthy male volunteers. 3. Glycopyrrolate decreased the mean (+/-SD)
      ApEn from 1.46 +/- 0.18 to 0.85 +/- 0.24 (P = 0.001 in comparison with the
      control group), and increased the short-term (alpha 1) and intermediate-term
      (alpha 2) fractal scaling exponents of DFA, alpha 1 from 0.96 +/- 0.19 to 1.43 +/
      0.29 (P = 0.003) and alpha 2 from 1.13 +/- 0.10 to 1.34 +/- 0.14 (P < 0.001). 4.
      Decrease in fixed respiration rate from 15 to 6 breaths min-1 increased alpha 1
      from 0.83 +/- 0.25 to 1.18 +/- 0.27 (P < 0.001), but decreased alpha 2 from 0.88
      +/- 0.09 to 0.45 +/- 0.17 (P < 0.001) and ApEn from 1.26 +/- 0.12 to 1.10 +/-
      0.14 (P = 0.028). Rapid breathing (24 min-1) had no influence on these non-linear
      measures of HR variability. Hyperventilation (15 min-1, tidal volume increased
      voluntarily by 0.5 l) decreased alpha 1 from 0.83 +/- 0.25 to 0.66 +/- 0.28 (P =
      0.002) but did not affect alpha 2 or ApEn. 5. To conclude, vagal blockade alters
      the fractal scaling properties of R-R intervals (alpha 1, alpha 2) and reduces
      the complexity (ApEn) of HR behaviour. Both the fractal and complexity measures
      of HR variability can also be influenced by changes in the breathing pattern.

PMID- 14690493
TI  - Adenosine affects the calcium dynamics of rat portal vein.
AB  - 1. The present study was carried out to characterize the effect of adenosine on
      calcium dynamics in the rat portal vein. Isolated portal vein of male albino rats
      was used as the experimental model as it exhibits autorhythmicity. 2. Adenosine
      and its analogues 2-CAD, N6-CHA and NECA were used to characterize the type of
      adenosine receptor involved and 2-CAD was used along with adenosine throughout
      the other part of study to characterize the effect of adenosine on Ca2+ dynamics.
      Adenosine and its analogues were found to inhibit the spontaneous contractions of
      rat portal vein in a concentration-related manner. The order of potency was NECA
      > 2-CAD > N6-CHA > adenosine. Incubation of the tissue with CGS-15943A, an
      adenosine receptor antagonist, had a per se enhancing effect on autorhythmicity.
      Adenosine and 2-CAD failed to reverse the contractile response produced by
      hypertonic KCl (80 or 30 mM). Whereas adenosine and 2-CAD effectively relaxed the
      tissues contracted with phenylephrine (10(-5) m). 3. Preincubation of the tissue
      with 2-CAD (10(-4), 10(-5) or 10(-6) m) for 5 min raised the threshold
      concentration of CaCl2 to evoke contractile response and also significantly
      increased the mean EC50 values of CaCl2. Nifedipine was found to be more potent
      than 2-CAD on Ca2+ channels. 4. The results of the present study suggest that the
      endogenous adenosine plays a significant role in producing vascular relaxation
      through the participation of A2 receptor subtype. This effect may be due to its
      inhibitory effect on release of Ca2+ from the intracellular stores. Further to
      this effect, 2-CAD had a major inhibitory effect on voltage-operated Ca2+
      channels compared with receptor-operated Ca2+ channels. 5. It can be concluded
      that adenosine through its A2 receptor produces vasorelaxant effect by
      interfering with the release of Ca2+ from the intracellular stores coupled with
      influx of Ca2+ from the extracellular sources.

PMID- 14690494
TI  - Demonstration of functional receptors for noradrenaline and adenosine-5'
      triphosphate, but not for prostaglandin E2, in HT-29 human colon cancer cell
      line.
AB  - 1. The aim of the current study was to investigate in HT-29 human colon cancer
      cell line, the existence of functional receptors for the signalling molecules,
      noradrenaline (NA), prostaglandin E2 (PGE2), and adenosine-5'-triphosphate (ATP).
      2. We utilized microphysiometry, which monitors on-line extracellular
      acidification rate (ECAR) as a measure of cellular metabolic activity, and how
      this variable is altered by signalling molecules. 3. Challenge with NA (5.9
      microM) resulted in an increase in ECAR by approximately 24% of basal. 4. PGE2
      (0.0284, 0.284 and 2.84 microM) hardly affected ECAR. 5. ATP (100 microM)
      elicited a biphasic effect on ECAR (increase and decrease in ECAR by about 58 and
      10% of basal, respectively). 6. HT-29 cells were shown to express COX-2 by
      immunocytochemistry. 7. These data suggest the presence of functional receptors
      for NA and ATP, but not for PGE2 in HT-29 human colon cancer cell line.

PMID- 14690495
TI  - Out with a bang! Tetrahymena as a model system to study secretory granule
      biogenesis.
AB  - The release of polypeptides in response to extracellular cues is a notable
      feature of endocrine, exocrine and neuronal cells, and is based on regulated
      exocytosis via dense-core secretory granules. There is interest in this mode of
      secretion because of its importance in human physiology and also because
      regulated exocytosis reflects a complex pathway of membrane traffic that includes
      compartment-specific reversible macromolecular assembly, coat-independent vesicle
      budding, maturation/remodeling of both lumenal and membrane constituents, and
      stimulus-dependent membrane fusion. Secretory granules are absent in most
      unicellular model organisms but are highly developed in the Ciliates, which
      therefore offer attractive systems to study these phenomena. In Tetrahymena
      thermophila, biochemical and genetic approaches have begun yielding insights into
      issues ranging from control of granule core assembly, based on reverse genetic
      analysis of granule cargo, to questions about factors involved in granule
      biogenesis, based on random mutational approaches.

PMID- 14690496
TI  - How to roll an endothelial cigar: the biogenesis of Weibel-Palade bodies.
AB  - Weibel-Palade bodies (WPB) are the regulated secretory organelles of endothelial
      cells. These cigar-shaped membrane-bound structures function in both hemostasis
      and inflammation but their biogenesis is poorly understood. Here, we review what
      is currently known about their formation. The content of WPBs is dominated by the
      hemostatic factor von Willebrand factor (VWF), whose complex biogenesis ends in
      the formation of high molecular weight multimers. VWF is also organized into
      proteinaceous tubules which underlie the striated interior of WPBs as seen in the
      EM. VWF expression is necessary for formation of WPBs, and its heterologous
      expression can even lead to the specific recruitment of WPB membrane proteins,
      including the leukocyte receptor P-selectin, the tetraspanin CD63, and Rab27a.
      Unusually, the VWF propeptide is implicated in the biogenesis of WPBs, being
      essential for formation of the storage compartment. The elongation of the cigars
      and the formation of the tubules are determined by non-covalent interactions
      between pro- and mature VWF proteins. Surprisingly, high molecular weight
      multimers seem neither necessary nor sufficient to trigger formation of a storage
      compartment, and do not seem to have any role in WPB biogenesis. Von Willebrand's
      disease, usually caused by mutations within VWF, has provided many of the
      insights into the way in which VWF drives the formation of these organelles.

PMID- 14690497
TI  - Gamma-COP appendage domain - structure and function.
AB  - COPI-coated vesicles mediate retrograde transport from the Golgi back to the ER
      and intra-Golgi transport. The cytosolic precursor of the COPI coat, the
      heptameric coatomer complex, can be thought of as composed of two subcomplexes.
      The first consists of the beta-, gamma-, delta- and zeta-COP subunits which are
      distantly homologous to AP clathrin adaptor subunits. The second consists of the
      alpha-, beta'- and epsilon-COP subunits. Here, we present the structure of the
      appendage domain of gamma-COP and show that it has a similar overall fold as the
      alpha-appendage of AP2. Again, like the alpha-appendage the gamma-COP appendage
      possesses a single protein/protein interaction site on its platform subdomain. We
      show that in yeast this site binds to the ARFGAP Glo3p, and in mammalian gamma
      COP this site binds to a Glo3p orthologue, ARFGAP2. On the basis of mutations in
      the yeast homologue of gamma-COP, Sec21p, a second binding site is proposed to
      exist on the gamma-COP appendage that interacts with the alpha,beta',epsilon COPI
      subcomplex.

PMID- 14690498
TI  - Endoplasmic reticulum-localized amyloid beta-peptide is degraded in the cytosol
      by two distinct degradation pathways.
AB  - The paradigm of endoplasmic reticulum (ER)-associated degradation (ERAD) holds
      that misfolded secretory and membrane proteins are translocated back to the
      cytosol and degraded by the proteasome in a coupled process. Analyzing the
      degradation of ER-localized amyloid beta-peptide (Abeta), we found a divergence
      from this general model. Cell-free reconstitution of the export in
      biosynthetically loaded ER-derived brain microsomes showed that the export was
      mediated by the Sec61p complex and required a cytosolic factor but was
      independent of ATP. In contrast to the ERAD substrates known so far, the exported
      Abeta was degraded by both, a proteasome-dependent and a proteasome-independent
      pathway. RNA interference experiments in Abeta-transfected cells identified the
      protease of the proteasome-independent pathway as insulin-degrading enzyme (IDE).
      The IDE-mediated clearance mechanism for ER-localized Abeta represents an as yet
      unknown type of ERAD which is not entirely dependent on the proteasome.

PMID- 14690499
TI  - Multiple phosphorylation events regulate the subcellular localization of GGA1.
AB  - GGAs comprise a family of Arf-dependent coat proteins or adaptors that regulate
      vesicle traffic from the trans-Golgi network (TGN). GGAs bind activated Arf,
      cargo, and additional components necessary for vesicle budding through
      interactions with their four functional domains: VHS, GAT, hinge, and GAE. We
      identified three sites of phosphorylation in GGA1 by tandem mass spectrometry:
      S268 and T270 in the GAT domain and S480 in the hinge. Expression of HA-GGA1 in
      mammalian cells and comparison to endogenous GGA1 confirmed their localization to
      late Golgi compartments. In contrast, mutations that mimic the phosphoprotein (HA
      GGA1[S268D] or HA-GGA1[T270D]) at either of the sites in the GAT domain caused a
      decrease in the colocalization with markers of the Golgi and TGN and an increase
      in puncta in cytoplasm. Quantitative comparisons of the extent of colocalization
      of GGA1 proteins with the known components of GGA1 vesicles revealed that the
      composition of those markers tested in HA-GGA1[S268D] and HA-GGA1[T270D] vesicles
      were indistinguishable from those of HA-GGA1 vesicles. We conclude that
      phosphorylation of the GAT domain can stabilize the coat proteins bound and thus
      regulate the rate of coat protein dissociation.

PMID- 14690500
TI  - The plasma membrane aquaporin NtAQP1 is a key component of the leaf unfolding
      mechanism in tobacco.
AB  - Epinastic leaf movement of tobacco is based on differential growth of the upper
      and lower leaf surface and is distinct from the motor organ-driven mechanism of
      nyctinastic leaf movement of, for example, mimosa species. The epinastic leaf
      movement of tobacco is observed not only under diurnal light regimes but also in
      continuous light, indicating a control by light and the circadian clock. As the
      transport of water across membranes by aquaporins is an important component of
      rapid plant cell elongation, the role of the tobacco aquaporin Nt aquaporin
      (AQP)1 in the epinastic response was studied in detail. In planta NtAQP1
      luciferase (LUC) activity studies, Northern and Western blot analyses
      demonstrated a diurnal and circadian oscillation in the expression of this plasma
      membrane intrinsic protein (PIP)1-type aquaporin in leaf petioles, exhibiting
      peaks of expression coinciding with leaf unfolding. Cellular water permeability
      of protoplasts isolated from leaf petioles was found to be high in the morning,
      i.e. during the unfolding reaction, and low in the evening. Moreover, diurnal
      epinastic leaf movement was shown to be reduced in transgenic tobacco lines with
      an impaired expression of NtAQP1. It is concluded that the cyclic expression of
      PIP1-aquaporin represents an important component of the leaf movement mechanism.

PMID- 14690501
TI  - Membrane-bound fatty acid desaturases are inserted co-translationally into the ER
      and contain different ER retrieval motifs at their carboxy termini.
AB  - Fatty acid desaturases (FADs) play a prominent role in plant lipid metabolism and
      are located in various subcellular compartments, including the endoplasmic
      reticulum (ER). To investigate the biogenesis of ER-localized membrane-bound
      FADs, we characterized the mechanisms responsible for insertion of Arabidopsis
      FAD2 and Brassica FAD3 into ER membranes and determined the molecular signals
      that maintain their ER residency. Using in vitro transcription/translation
      reactions with ER-derived microsomes, we show that both FAD2 and FAD3 are
      efficiently integrated into membranes by a co-translational, translocon-mediated
      pathway. We also demonstrate that while the C-terminus of FAD3 (-KSKIN) contains
      a functional prototypic dilysine ER retrieval motif, FAD2 contains a novel C
      terminal aromatic amino acid-containing sequence (-YNNKL) that is both necessary
      and sufficient for maintaining localization in the ER. Co-expression of a
      membrane-bound reporter protein containing the FAD2 C-terminus with a dominant
      negative mutant of ADP-ribosylation factor (Arf)1 abolished transient
      localization of the reporter protein in the Golgi, indicating that the FAD2
      peptide signal acts as an ER retrieval motif. Mutational analysis of the FAD2 ER
      retrieval signal revealed a sequence-specific motif consisting of Phi-X-X-K/R/D/E
      Phi-COOH, where -Phi- are large hydrophobic amino acid residues. Interestingly,
      this aromatic motif was present in a variety of other known and putative ER
      membrane proteins, including cytochrome P450 and the peroxisomal biogenesis
      factor Pex10p. Taken together, these data describe the insertion and retrieval
      mechanisms of FADs and define a new ER localization signal in plants that is
      responsible for the retrieval of escaped membrane proteins back to the ER.

PMID- 14690502
TI  - The universally conserved HCF101 protein is involved in assembly of [4Fe-4S]
      cluster-containing complexes in Arabidopsis thaliana chloroplasts.
AB  - The seedling-lethal nuclear Arabidopsis hcf101 (high chlorophyll fluorescence)
      mutant is impaired in photosynthesis and complemented by the wild-type HCF101
      cDNA. Photosystem I (PSI) activity is abolished, and PSI core complexes fail to
      accumulate in hcf101, whereas levels of other thylakoid membrane proteins are
      unaffected. Northern and in vivo labelling analyses as well as studies on
      polysome loading show that PSI transcript levels and translation rates of
      proteins, which belong to PSI, are normal in hcf101. PSI-specific fluorescence at
      77 K is shifted from 735 to 728 nm in hcf101, indicating that exitons cannot
      efficiently be transferred to the PSI reaction centre, whereby the PSI antenna is
      almost unaffected. Mutant plants not only fail to accumulate mature PSI, which
      contains three [4Fe-4S]clusters (FSCs), but also are characterized by reduced
      levels of the soluble FSC-containing complex ferredoxin-thioredoxin reductase
      (FTR) in the stroma. Inhibited FTR maturation is not a secondary effect stemming
      from lack of PSI because the mutant hcf145, which also lacks PSI, accumulates FTR
      at normal levels. Levels of the [2Fe-2S] cluster-containing soluble and membrane
      proteins, ferredoxin and PetC, respectively, were unchanged in hcf101 plants.
      These data suggest a specific role of HCF101 in FSC biogenesis. HCF101 is plastid
      localized and belongs to an ancient and universally conserved family of P-loop
      ATPases previously designated as the 'MRP' (metGrelated protein) family. The
      function identified for HCF101 suggests a new designation, FSC, for this family.

PMID- 14690503
TI  - Pathogenesis-related protein 10 isolated from hot pepper functions as a
      ribonuclease in an antiviral pathway.
AB  - A hot pepper (Capsicum annuum) cDNA clone encoding pathogenesis-related protein
      10 (CaPR-10) was isolated by differential screening of a cDNA library prepared
      from pepper leaves inoculated with tobacco mosaic virus pathotype (TMV-P0). CaPR
      10 transcripts were induced in the incompatible interaction with TMV-P0 or
      Xanthomonas campestris pv. vesicatoria (Xcv) but not induced in the compatible
      interaction. Characterization of enzymatic properties of CaPR-10 indicated that
      the recombinant protein exhibits a ribonucleolytic activity against TMV RNA, as
      well as against pepper total RNA, and shows its putative antiviral activity in
      several conditions. The CaPR-10 protein existed at very low level in leaf tissue
      but was dramatically induced as soon as plants were inoculated with TMV-P0, and
      this was correlated with the increase of its ribonucleolytic activity. Immunoblot
      analysis and pull-down assays using proteins extracted from pepper leaves showed
      that TMV-P0 inoculation led to the phosphorylation of CaPR-10, a modification
      that should affect its capacity for RNase function. We present data that the
      induction and subsequent phosphorylation of CaPR-10 increased its ribonucleolytic
      activity to cleave invading viral RNAs, and this activity should be important to
      its antiviral pathway during viral attack in vivo.

PMID- 14690504
TI  - Cytoplasmic regulation of the accumulation of nuclear-encoded proteins in the
      mitochondrial proteome of maize.
AB  - Mitochondria from normal (NA)- and Texas (T)-cytoplasm maize (Zea mays L.) were
      purified from unpollinated ears via Percoll centrifugation. Approximately 300
      mitochondrial proteins were resolved using two-dimensional (2-D) electrophoresis.
      The 197 most abundant proteins were analyzed by matrix-assisted laser desorption
      ionization time-of-flight (MALDI-ToF) mass spectrometry involving overlapping pH
      gradients (pH 4-7 and 6-9). Database searches identified 58 genes that encode 100
      of these protein spots. Functions could be predicted for 38 of the 58 genes
      (66%). All but one of these genes are located in the nuclear genome. Thirteen per
      cent of the analyzed protein spots (25 out of 197) exhibited at least a threefold
      difference in accumulation between the mitochondrial proteomes of NA- or T
      cytoplasm maize plants that had essentially identical nuclear genomes. As most of
      these proteins were nuclear-encoded, these findings demonstrate that the genotype
      of a mitochondrion can regulate the accumulation of the nuclear-encoded fraction
      of its proteome. About half (27 out of 58) of the maize mitochondrial proteins
      identified in this study were not recovered in previous analyses of the
      Arabidopsis and rice mitochondrial proteomes.

PMID- 14690505
TI  - Salicylic acid regulates flowering time and links defence responses and
      reproductive development.
AB  - Flowering relies on signaling networks that integrate endogenous and external
      cues. Normally, plants flower at a particular season, reflecting day length
      and/or temperature cues. However, plants can surpass this seasonal regulation and
      show precocious flowering under stress environmental conditions. Here, we show
      that UV-C light stress activates the transition to flowering in Arabidopsis
      thaliana through salicylic acid (SA). Moreover, SA also regulates flowering time
      in non-stressed plants, as SA-deficient plants are late flowering. The regulation
      of flowering time by SA seems to involve the photoperiod and autonomous pathways,
      but it does not require the function of the flowering time genes CONSTANS (CO),
      FCA, or FLOWERING LOCUS C (FLC).

PMID- 14690506
TI  - New plant growth-modifying properties of the Agrobacterium T-6b oncogene revealed
      by the use of a dexamethasone-inducible promoter.
AB  - Agrobacterium 6b oncogenes induce tumours on Nicotiana glauca and enations and
      associated modifications in transgenic N. tabacum plants. 2x35S-AB-6b tobacco
      rootstocks produced a graft-transmissible factor that induced enations in wild
      type scions; the nature of this enation factor remains to be identified. Here, we
      report on the properties of tobacco plants carrying a dexamethasone-inducible T
      6b gene (dex-T-6b). Induction with dex led to complex growth modifications, many
      of which have not been reported previously. Modifications were only found in
      growing tissues; mature tissues remained unaffected. Growth could be either
      stimulated or inhibited. Dex induction of young plants led to morphogenetic
      gradients that included enations, tubular leaves and fragmented leaf primordia.
      Root elongation was increased or slowed down, while radial root growth was
      strongly enhanced. Additional cell divisions were found in the root pericycle and
      vasculature. Enation factor import from mature tissues did not have the same
      effects on growing tissues as local T-6b synthesis: normal scions grafted on
      induced dex-T-6b rootstocks formed enations, whereas local dex-T-6b induction at
      the shoot apex led to numerous dark-green spots on the abaxial side of the
      leaves. In leaf patch assays, the 23-kDa T-6b protein was found to move through
      leaves and to enter the vascular system. This and the fact that rootstocks of
      spontaneous tobacco enation mutants did not modify wild-type scions contrary to
      6b plants indicate that the 6b protein might be the enation factor.

PMID- 14690507
TI  - GIP, a Petunia hybrida GA-induced cysteine-rich protein: a possible role in shoot
      elongation and transition to flowering.
AB  - The Petunia hybrida GA-induced proteins (GIPs) belong to a large group of
      proteins identified in numerous plant species. These proteins share a similar C
      terminal region containing 12 cysteine residues in conserved positions. To date,
      the function of these proteins remains unclear. We previously found that GIP1
      expression coincides with cell elongation in stems and flowers and is induced by
      gibberellic acid (GA3). Transient expression of a GIP1:green fluorescent protein
      (GFP) fusion in tobacco bright yellow 2 (BY2) cells and immunoblot analyses
      suggest microsomal compartmentalization with possible endoplasmic reticulum (ER)
      localization. However, the polyclonal anti-GIP1 antibodies also reacted with
      proteins extracted from the cell wall. Three novel GIP homologs, GIP2, GIP4, and
      GIP5, were isolated. While GIP4, similar to GIP1, is putatively localized to the
      ER membrane, the cleavable hydrophobic N-terminal sequences of GIP2 and GIP5
      suggest cell wall localization. GIP1 and GIP2 are expressed during cell
      elongation, whereas GIP4 and GIP5 are expressed during cell division;
      nevertheless, they all were induced by GA3. We generated transgenic petunia in
      which we repressed the putative cell wall protein GIP2. The transgenic plants
      exhibited late flowering and reduced stem elongation. These phenotypic
      alterations were found under low, but not moderate-high temperatures, suggesting
      functional redundancy under normal growth conditions. The expression pattern and
      cellular localization of GIP2, its regulation by GA, and the phenotype of the
      transgenic plants suggest a role in GA-mediated cell elongation and transition to
      flowering.

PMID- 14690508
TI  - Involvement of the R2R3-MYB, AtMYB61, in the ectopic lignification and dark
      photomorphogenic components of the det3 mutant phenotype.
AB  - Overexpression of a pine MYB, PtMYB4, in Arabidopsis caused ectopic lignin
      deposition and allowed the plants to undergo photomorphogenesis even when they
      were grown in the dark. The phenotype caused by PtMYB4 overexpression was
      reminiscent of the previously characterised dark-photomorphogenic mutant, de
      etiolated 3 (det3); consequently, we tested the hypothesis that MYB misexpression
      may explain aspects of the det3 phenotype. We show here that AtMYB61, a member of
      the Arabidopsis R2R3-MYB family, is misexpressed in the det3 mutant. Semi
      quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) experiments
      suggested that AtMYB61 was misexpressed in a det3 background relative to wild
      type plants. Examination of AtMYB61 promoter activity in a det3 background showed
      that the spatial control of AtMYB61 expression was lost. In order to determine if
      such misexpression could explain the mutant phenotype, AtMYB61 was overexpressed
      in wild-type Arabidopsis plants. Transgenic plants that overexpressed AtMYB61 had
      the same ectopic lignification and dark-photomorphogenic phenotype as that of the
      det3 mutant. In order to test if AtMYB61 was necessary for these aspects of the
      det3 phenotype, AtMYB61 expression was downregulated in det3 plants in both
      antisense and sense suppression experiments. Suppression of AtMYB61 in a det3
      mutant background restored all mutant phenotypes of the det3 mutant associated
      with development in the dark. Taken together, these results suggest that AtMYB61
      misexpression was both sufficient and necessary to explain the ectopic
      lignification and dark-photomorphogenic phenotypes of the det3 mutant.

PMID- 14690509
TI  - Cross-species microarray transcript profiling reveals high constitutive
      expression of metal homeostasis genes in shoots of the zinc hyperaccumulator
      Arabidopsis halleri.
AB  - Arabidopsis halleri ssp. halleri (accession Langelsheim) is a naturally selected
      zinc (Zn)- and cadmium-tolerant Zn hyperaccumulator. This plant differs
      strikingly from its close relative A. thaliana by accumulating Zn specifically in
      above-ground tissues. A. thaliana GeneChips were used in order to identify, on a
      transcriptome-wide scale, genes with a potential involvement in cellular metal
      uptake or detoxification in the shoots of A. halleri. Compared to A. thaliana,
      transcript abundance of several genes was found and confirmed to be substantially
      higher in A. halleri after 4 days of exposure to low as well as high Zn
      concentrations in the hydroponic culture medium. The identified candidate genes
      encode proteins closely related to the following A. thaliana proteins: AtZIP6, a
      putative cellular Zn uptake system and member of the zinc-regulated transporter
      (ZRT)-iron regulated transporter (IRT)-like protein (ZIP)-family of metal
      transporters, the putative P-type metal ATPase AtHMA3, the cation diffusion
      facilitator ZAT/AtCDF1, and the nicotianamine synthase AtNAS3. Heterologous
      expression in mutant strains of the yeast Saccharomyces cerevisiae suggested that
      AhHMA3, AhCDF1-3, and AhNAS3 can function in cellular Zn detoxification. Our data
      indicate that, at the transcript level, the Zn tolerance strategy of A. halleri
      involves high constitutive expression of metal homeostasis genes in the shoots to
      accommodate higher basal levels of Zn accumulation, and possibly to prepare for
      sudden increases in Zn influx into shoot cells. Furthermore, profiling of metal
      homeostasis gene transcripts in shoot and root tissues by real-time RT-PCR
      indicated that A. halleri and A. thaliana respond differently to changes in plant
      Zn status.

PMID- 14690510
TI  - Comparative microarray analysis of Arabidopsis thaliana and Arabidopsis halleri
      roots identifies nicotianamine synthase, a ZIP transporter and other genes as
      potential metal hyperaccumulation factors.
AB  - The hyperaccumulation of zinc (Zn) and cadmium (Cd) is a constitutive property of
      the metallophyte Arabidopsis halleri. We therefore used Arabidopsis GeneChips to
      identify genes more active in roots of A. halleri as compared to A. thaliana
      under control conditions. The two genes showing highest expression in A. halleri
      roots relative to A. thaliana roots out of more than 8000 genes present on the
      chip encode a nicotianamine (NA) synthase and a putative Zn2+ uptake system. The
      significantly higher activity of these and other genes involved in metal
      homeostasis under various growth conditions was confirmed by Northern and RT-PCR
      analyses. A. halleri roots also show higher NA synthase protein levels.
      Furthermore, we developed a capillary liquid chromatography electrospray
      ionization quadrupole time-of-flight mass spectrometry (CapLC-ESI-QTOF-MS)-based
      NA analysis procedure and consistently found higher NA levels in roots of A.
      halleri. Expression of a NA synthase in Zn2+-hypersensitive Schizosaccharomyces
      pombe cells demonstrated that formation of NA can confer Zn2+ tolerance. Taken
      together, these observations implicate NA in plant Zn homeostasis and NA synthase
      in the hyperaccumulation of Zn by A. halleri. Furthermore, the results show that
      comparative microarray analysis of closely related species can be a valuable tool
      for the elucidation of phenotypic differences between such species.

PMID- 14690511
TI  - Rac regulation of NtrbohD, the oxidase responsible for the oxidative burst in
      elicited tobacco cell.
AB  - Five cDNAs encoding Rac protein homologues to the Rho-related proteins from
      plants (Rop) were isolated in tobacco, and the function of one of them, Ntrac5,
      was studied. The Ntrac5 mRNA is repressed when tobacco leaves and cells are
      treated with the fungal elicitor cryptogein. Tobacco cells were transformed with
      sense constructs of Ntrac5 or Ntrac5V15, encoding the native GTP/GDP-bound form
      of this Rac protein homologue or the constitutively active mutant in its GTP
      bound form, respectively. Immunological studies indicate that the corresponding
      protein is continuously located on the plasma membrane (PM). Both types of
      transformed cells show the same extra-cellular alkalinization as the control, but
      a high decrease in the active oxygen species (AOS) production after elicitation
      with cryptogein. Moreover, the regulation of NtrbohD, the oxidase involved in AOS
      production upon elicitation, is affected at both transcriptional and
      translational levels in cells overexpressing Ntrac5. Thus, Ntrac5 could be
      considered as a negative regulator of NtrbohD.

PMID- 14690512
TI  - Two functionally different vacuoles for static and dynamic purposes in one plant
      mesophyll leaf cell.
AB  - It is a common belief that plant mesophyll cells are occupied up to 95% by a
      single multipurpose vacuole. The common ice plant, Mesembryanthemum crystallinum
      L., however, requires two contrasting functions of the vacuole under salt stress.
      Large amounts of NaCl have to be sequestered permanently for osmotic purpose and
      for protecting the cytoplasm from NaCl toxicity. A dynamic exchange with the
      cytoplasm is required because photosynthesis proceeds under these conditions via
      the metabolic cycle of crassulacean acid metabolism (CAM). Nocturnally acquired
      CO2 must be kept as malate in the vacuole and re-mobilized in the daytime. Here,
      we show that two large independent types of vacuoles with different transport
      properties meet the requirements for the contrasting functions within the same
      cell.

PMID- 14690513
TI  - Establishing an efficient Ac/Ds tagging system in rice: large-scale analysis of
      Ds flanking sequences.
AB  - A two-element Activator/Dissociation (Ac/Ds) gene trap system was successfully
      established in rice (Oryza sativa ssp. japonica cv. Nipponbare) to generate a
      collection of stable, unlinked and single-copy Ds transposants. The germinal
      transposition frequency of Ds was estimated as an average of 51% by analyzing
      4413 families. Study of Ds transposition pattern in siblings revealed that 79%
      had at least two different insertions, suggesting late transposition during rice
      development. Analysis of 2057 Ds flanking sequences showed that 88% of them were
      unique, whereas the rest within T-DNA. The insertions were distributed randomly
      throughout the genome; however, there was a bias toward chromosomes 4 and 7,
      which had two times as many insertions as that expected. A hot spot for Ds
      insertions was identified on chromosome 7 within a 40-kbp region. One-third of Ds
      flanking sequences was homologous to either proteins or rice expressed sequence
      tags (ESTs), confirming a preference for Ds transposition into coding regions.
      Analysis of 200 Ds lines on chromosome 1 revealed that 72% insertions were found
      in genic region. Anchoring of more than 800 insertions to yeast artificial
      chromosome (YAC)-based EST map showed that Ds transposes preferentially into
      regions rich in expressed sequences. High germinal transposition frequency and
      independent transpositions among siblings show that the efficiency of this system
      is suitable for large-scale transposon mutagenesis in rice.

PMID- 14690514
TI  - Applications of nucleic acid technology in the CNS.
AB  - This review examines applications of nucleic acid technology in the form of
      catalytic nucleic acids (ribozymes and DNAzymes) and RNA interference (RNAi) in
      the CNS. The basic mechanism of catalytic nucleic acids and RNAi is reviewed, and
      potentials and problems highlighted. Recent advances in chemical modifications
      and delivery techniques are summarized. Applications in the CNS, including their
      use in primary neuronal cells, organotypic slice culture and the brain in vivo
      are further discussed.

PMID- 14690515
TI  - Determination of the oxidation states of manganese in brain, liver, and heart
      mitochondria.
AB  - Excess brain manganese can produce toxicity with symptoms that resemble those of
      Parkinsonism and causes that remain elusive. Manganese accumulates in
      mitochondria, a major source of superoxide, which can oxidize Mn2+ to the
      powerful oxidizing agent Mn3+. Oxidation of important cell components by Mn3+ has
      been suggested as a cause of the toxic effects of manganese. Determining the
      oxidation states of intramitochondrial manganese could help to identify the
      dominant mechanism of manganese toxicity. Using X-ray absorbance near edge
      structure (XANES) spectroscopy, we have characterized the oxidation state of
      manganese in mitochondria isolated from brain, liver, and heart over
      concentrations ranging from physiological to pathological. Results showed that
      (i) spectra from different model manganese complexes of the same oxidation state
      were similar to each other and different from those of other oxidation states and
      that the position of the absorption edge increases with oxidation state; (ii)
      spectra from intramitochondrial manganese in isolated brain, heart and liver
      mitochondria were virtually identical; and (iii) under these conditions
      intramitochondrial manganese exists primarily as a combination of Mn2+ complexes.
      No evidence for Mn3+ was detected in samples containing more than endogenous
      manganese levels, even after incubation under conditions promoting reactive
      oxygen species (ROS) production. While the presence of Mn3+ complexes cannot be
      proven in the spectrum of endogenous mitochondrial manganese, the shape of this
      spectrum could suggest the presence of Mn3+ near the limit of detection, probably
      as MnSOD.

PMID- 14690516
TI  - Oligomerization and neurotoxicity of the amyloid ADan peptide implicated in
      familial Danish dementia.
AB  - Familial Danish dementia (FDD) is a rare neurodegenerative disorder, which is
      pathologically characterized by widespread cerebral amyloid angiopathy,
      parenchymal protein deposits and neurofibrillary degeneration. FDD is associated
      with mutation in the BRI gene. In FDD a decamer duplication between codons 265
      and 266 in the 3' region of the BRI gene originates an amyloid peptide named
      ADan, 11 residues longer than the wild-type peptide produced from the normal BRI
      gene. ADan deposits have been found widely distributed in the CNS of FDD cases.
      The deposits of ADan are predominantly non-fibrillar aggregates. We show here
      that synthetic ADan forms oligomers in vitro, seen by Tricine-PAGE and gel
      filtration, and higher aggregates, which are seen by atomic force spectroscopy
      and electron microscopy as carrot-shaped objects that bunch together. Here we
      report that oligomeric ADan is toxic to neuronal cell lines. We find that the
      soluble non-fibrillar oligomeric species of both the reduced and oxidized forms
      of ADan are toxic. These results support the idea that the non-fibrillar soluble
      aggregates are the pathogenic species, which may play a central role in the
      pathogenesis of FDD, and imply that similar mechanism may also be involved in
      other neurodegenerative diseases associated with amyloid deposits.

PMID- 14690517
TI  - The localisation of the extraneuronal monoamine transporter (EMT) in rat brain.
AB  - The extraneuronal monoamine transporter plays an important role in the
      inactivation of monoamine transmitters. A basal extraneuronal tissue expression
      of this transporter has been reported, but it is also expressed in CNS glia. As
      little is known about the expression pattern and the function of the
      extraneuronal monoamine transporter in the brain, we performed a detailed
      investigation. Firstly, a northern blot analysis of different rat organs revealed
      that the transporter is strongly expressed in placenta, lung and heart and less
      prominently in the whole brain, brain stem, intestine, testis, epididymis,
      stomach, kidney and skeletal muscle. It was not expressed in cerebellum, liver
      and embryo. Using an in situ hybridization to the rat brain, we detected a marked
      and highly confined expression of the extraneuronal monoamine transporter in the
      area postrema, but in no other brain areas. These findings were confirmed by
      polyclonal antibodies against rat extraneuronal monoamine transporter showing an
      intensive signal in the area postrema, although a few cells in the cerebellum and
      the brain stem also showed a signal. Additionally, a partly overlapping
      expression pattern of the monoamine oxidase-B was detected. Summarizing, we
      firstly describe a marked and highly confined expression of the extraneuronal
      monoamine transporter in the rat area postrema by in situ hybridisation which may
      play a role in physiological functions of this circumventricular organ such as
      emesis, food intake and the regulation of cardiovascular functions.

PMID- 14690518
TI  - Dephosphorylation of microtubule-associated protein tau by protein phosphatase 5.
AB  - Protein phosphatase 5 (PP5) is a 58-kDa novel phosphoseryl/phosphothreonyl
      protein phosphatase. It is ubiquitously expressed in all mammalian tissues
      examined, with a high level in the brain, but little is known about its
      physiological substrates. We found that this phosphatase dephosphorylated
      recombinant tau phosphorylated with cAMP-dependent protein kinase and glycogen
      synthase kinase-3beta, as well as abnormally hyperphosphorylated tau isolated
      from brains of patients with Alzheimer's disease. The specific activity of PP5
      toward tau was comparable to those reported with other protein substrates
      examined to date. The PP5 activity toward tau was stimulated by arachidonic acid
      by 30- to 45-fold. Immunostaining demonstrated that PP5 was primarily cytoplasmic
      in PC12 cells and in neurons of postmortem human brain tissue. A small pool of
      PP5 associated with microtubules. Expression of active PP5 in PC12 cells resulted
      in reduced phosphorylation of tau, suggesting that PP5 can also dephosphorylate
      tau in cells. These results suggest that PP5 plays a role in the
      dephosphorylation of tau and might be involved in the molecular pathogenesis of
      Alzheimer's disease.

PMID- 14690519
TI  - Expression of a novel neuropeptide, NVGTLARDFQLPIPNamide, in the larval and adult
      brain of Drosophila melanogaster.
AB  - Advances in mass spectrometry and the availability of genomic databases made it
      possible to determine the peptidome or peptide content of a specific tissue.
      Peptidomics by nanoflow capillary liquid chromatography tandem mass spectrometry
      of an extract of 50 larval Drosophila brains, yielded 28 neuropeptides. Eight
      were entirely novel and encoded by five not yet annotated genes; only two genes
      had a homologue in the Anopheles gambiae genome. Seven of the eight peptides did
      not show relevant sequence homology to any known peptide. Therefore, no evidence
      towards the physiological role of these 'orphan' peptides was available. We
      identified one of the eight peptides, IPNamide, in an extract of the Drosophila
      adult brain as well. Next, specific antisera were raised to reveal the
      distribution pattern of IPNamide and other peptides from the same precursor, in
      larval and adult brains by means of whole-mount immunocytochemistry and confocal
      microscopy. IPNamide immunoreactivity is abundantly present in both stages and a
      striking similarity was found between the distribution patterns of IPNamide and
      TPAEDFMRFamide, a member of the FMRFamide peptide family. Based on this
      distribution pattern, IPNamide might be involved in phototransduction, in
      processing sensory stimuli, as well as in controlling the activity of the
      oesophagus.

PMID- 14690520
TI  - Topiramate modulation of kainate-induced calcium currents is inversely related to
      channel phosphorylation level.
AB  - Topiramate (TPM) is a structurally novel broad-spectrum anticonvulsant known to
      modulate the activity of several ligand- and voltage-gated ion channels in
      neurons. These include an inhibitory effect on the AMPA and kainate subtypes of
      glutamate receptors, mixed modulatory effects (usually positive) on some types of
      GABAA receptors, negative modulatory effects on some types of voltage-gated Na+
      and Ca2+ channels, and a positive modulatory effect on at least one type of K+
      channel. The nature of these effects at the molecular level has not been
      established, but two previous studies have implicated the phosphorylation state
      of these receptor/channel complexes as an influencing factor in the activity of
      TPM. Here, we report that the ability of TPM to inhibit a kainate-induced
      accumulation of free Ca2+ in cultured neurons from rat cerebral cortex is
      inversely related to the level of cAMP-dependent protein kinase (cAPK) mediated
      phosphorylation of kainate-activated receptors/channels. Specifically, when cell
      cultures were pre-treated with forskolin or dibutyryl cAMP, indirect activators
      of cAPK, the activity of TPM was abolished, whereas when the cells were pre
      treated with H89, an inhibitor of cAPK, the relative activity of TPM was
      enhanced. The results of this study support the hypothesis that TPM binds to
      phosphorylation sites on AMPA and kainate receptors, but only in the
      dephosphorylated state and thereby exerts an allosteric modulatory effect on
      channel conductance.

PMID- 14690521
TI  - Identification of gene structure and subcellular localization of human centaurin
      alpha 2, and p42IP4, a family of two highly homologous, Ins 1,3,4,5-P4-/PtdIns
      3,4,5-P3-binding, adapter proteins.
AB  - Proteins which recognize the two messengers phosphatidylinositol 3,4,5
      trisphosphate (PtdInsP3), a membrane lipid, and inositol 1,3,4,5
      tetrakisphosphate (InsP4), a water-soluble ligand, play important roles by
      integrating external stimuli, which lead to differentiation, cell death or
      survival. p42IP4, a PtdInsP3/InsP4-binding protein, is predominantly expressed in
      brain. The recently described centaurin alpha2 of similar molecular mass which is
      58% identical and 75% homologous to the human p42IP4 orthologue, is expressed
      rather ubiquitously in many tissues. Here, elucidating the gene structure for
      both proteins, we found the human gene for centaurin alpha2 located on chromosome
      17, position 17q11.2, near to the NF1 locus, and human p42IP4 on chromosome 7,
      position 7p22.3. The two isoforms, which both have 11 exons and conserved
      exon/intron transitions, seem to result from gene duplication. Furthermore, we
      studied binding of the two second messengers, PtdInsP3 and InsP4, and subcellular
      localization of the two proteins. Using recombinant baculovirus we expressed
      centaurin alpha2 and p42IP4 in Sf9 cells and purified the proteins to
      homogeneity. Recombinant centaurin alpha2 bound both InsP4 and PtdInsP3 equally
      well in vitro. Furthermore, fusion proteins of centaurin alpha2 and p42IP4,
      respectively, with the green fluorescent protein (GFP) were expressed in HEK 293
      cells to visualize subcellular distribution. In contrast to p42IP4, which was
      distributed throughout the cell, centaurin alpha2 was concentrated at the plasma
      membrane already in unstimulated cells. The protein centaurin alpha2 was released
      from the membrane upon addition of wortmannin, which inhibits PI3-kinase. p42IP4,
      however, translocated to plasma membrane upon growth factor stimulation. Thus, in
      spite of the high homology between centaurin alpha2 and p42IP4 and comparable
      affinities for InsP4 and PtdInsP3, both proteins showed clear differences in
      subcellular distribution. We suggest a model, which is based on the difference in
      phosphoinositide binding stoichiometry of the two proteins, to account for the
      difference in subcellular localization.

PMID- 14690522
TI  - Modulation of beta-amyloid metabolism by non-steroidal anti-inflammatory drugs in
      neuronal cell cultures.
AB  - Alzheimer disease (AD) is characterized by cerebral deposits of beta-amyloid
      (Abeta) peptides, which are surrounded by neuroinflammatory cells.
      Epidemiological studies have shown that prolonged use of non-steroidal anti
      inflammatory drugs (NSAIDs) reduces the risk of developing AD. In addition,
      biological data indicate that certain NSAIDs specifically lower Abeta42 levels in
      cultures of peripheral cells independently of cyclooxygenase (COX) activity and
      reduce cerebral Abeta levels in AD transgenic mice. Whether other NSAIDs,
      including COX-selective compounds, modulate Abeta levels in neuronal cells
      remains unexploited. Here, we investigated the effects of compounds from every
      chemical class of NSAIDs on Abeta40 and Abeta42 secretion using both Neuro-2a
      cells and rat primary cortical neurons. Among non-selective NSAIDs, flurbiprofen
      and sulindac sulfide concentration-dependently reduced the secretion not only of
      Abeta42 but also of Abeta40. Surprisingly, both COX-2 (celecoxib; sc-125) or COX
      1 (sc-560) selective compounds significantly increased Abeta42 secretion, and
      either did not alter (sc-560; sc-125) or reduced (celecoxib) Abeta40 levels. The
      levels of betaAPP C-terminal fragments and Notch cleavage were not altered by any
      of the NSAIDs, indicating that gamma-secretase activity was not overall changed
      by these drugs. The present findings show that only a few non-selective NSAIDs
      possess Abeta-lowering properties and therefore have a profile potentially
      relevant to their clinical use in AD.

PMID- 14690523
TI  - Primed phosphorylation of tau at Thr231 by glycogen synthase kinase 3beta
      (GSK3beta) plays a critical role in regulating tau's ability to bind and
      stabilize microtubules.
AB  - Site-specific phosphorylation of tau negatively regulates its ability to bind and
      stabilize microtubule structure. Although tau is a substrate of glycogen synthase
      kinase 3beta (GSK3beta), the exact sites on tau that are phosphorylated by this
      kinase in situ have not yet been established, and the effect of these
      phosphorylation events on tau-microtubule interactions have not been fully
      elucidated. GSK3beta phosphorylates both primed and unprimed sites on tau, but
      only primed phosphorylation events significantly decrease the ability of tau to
      bind microtubules. The focus of the present study is on determining the
      importance of the GSK3beta-mediated phosphorylation of a specific primed site,
      Thr231, in regulating tau's function. Pre-phosphorylation of Ser235 primes tau
      for phosphorylation by GSK3beta at Thr231. Phosphorylation by GSK3beta of wild
      type tau or tau with Ser235 mutated to Ala decreases tau-microtubule
      interactions. However, when Thr231 alone or Thr231 and Ser235 in tau were mutated
      to Ala, phosphorylation by GSK3beta did not decrease the association of tau with
      the cytoskeleton. Further, T231A tau was still able to efficiently bind
      microtubules after phosphorylation by GSK3beta. Expression of each tau construct
      alone increased tubulin acetylation, a marker of microtubule stability. However,
      when cells were cotransfected with wild-type tau and GSK3beta, the level of
      tubulin acetylation was decreased to vector-transfected levels. In contrast,
      coexpression of GSK3beta with mutated tau (T231A/S235A) did not significantly
      decrease the levels of acetylated tubulin. These results strongly indicate that
      phosphorylation of Thr231 in tau by GSK3beta plays a critical role in regulating
      tau's ability to bind and stabilize microtubules.

PMID- 14690524
TI  - Phosphatidylinositol 3'-OH kinase and protein kinase A pathways mediate the anti
      apoptotic effect of pituitary adenylyl cyclase-activating polypeptide in cultured
      cerebellar granule neurons: modulation by ethanol.
AB  - Cerebellar granule neurons cultured in the presence of 5 mm KCl undergo
      spontaneous apoptosis, which is reduced by exposure to pituitary adenylyl cyclase
      activating polypeptide (PACAP). Previous work has suggested roles for the cyclic
      AMP/PKA and MAP kinase signaling pathways in the anti-apoptotic effect of PACAP.
      In the present study, the use of specific inhibitors confirmed the role of the
      cyclic AMP/PKA pathway, and also demonstrated a role for the phosphatidylinositol
      3'-OH kinase (PI 3-kinase) neuroprotective pathway in the action of PACAP.
      Ethanol exposure accelerates the anti-apoptotic effect of PACAP by a mechanism
      that involves the PKA and PI-3 kinase pathways. The results demonstrate that
      ethanol can increase neuroprotection induced by PACAP. As previous work has shown
      that ethanol can increase apoptosis of cerebellar granule neurons by inhibiting
      the protective effect of agents such as NMDA or IGF-1, the overall effect of
      ethanol on cerebellar neuron apoptosis during development may reflect the balance
      between inhibition and enhancement of the actions of various endogenous
      neuroprotective agents.

PMID- 14690525
TI  - Differential enantioselective effects of pentyl-4-yn-valproate on spatial
      learning in the rat, and neurite outgrowth and cyclin D3 expression in vitro.
AB  - Previously, we demonstrated the racemic form of the valproate (VPA) analogue, 2-n
      pentyl-4-pentynoic acid ([+/-]pentyl-4-yn-VPA), to be neuritogenic in vitro and
      to enhance cognition in vivo. To determine the enantioselectivity of these
      effects, the racemate and purified enantiomers of [+/-]pentyl-4-yn-VPA (84 mg/kg,
      i.p.) were administered to rodents 20 min prior to multi-session water maze
      training. The racemate and R-enantiomer significantly reduced escape latencies
      during water maze learning and enhanced its recall in a probe trial 3 days later.
      In contrast, S-pentyl-4-yn-VPA did not influence these behavioural parameters.
      The enantiomer-specific effects of [+/-]pentyl-4-yn-VPA were further
      discriminated in vitro using neuro 2A neuroblastoma and C6 glioma cell lines. In
      neuro 2A, the S-enantiomer induced profound neurite outgrowth at concentrations
      up to 0.5 mm, with the R-enantiomer and racemate being less neuritogenic.
      Immunoblot analysis of cyclin D3 expression in C6 glioma indicated the racemate
      and S-pentyl-4-yn-VPA to induce dose-dependent up-regulation of this protein,
      similar to that associated with G1-phase cell cycle arrest mediated by VPA,
      whereas R-pentyl-4-yn-VPA was without effect. These results indicate that the
      cognition-enhancing effects of pentyl-4-yn-VPA are due to the actions of the R
      enantiomer, and that cyclin D3 up-regulation and associated anti-proliferative
      and pro-differentiative actions are predominantly associated with the S
      enantiomer.

PMID- 14690526
TI  - Identification of differentially regulated transcripts in mouse striatum
      following methamphetamine treatment--an oligonucleotide microarray approach.
AB  - Methamphetamine is an addictive drug of abuse that can produce neurotoxic effects
      in dopamine nerve endings of the striatum. The purpose of this study was to
      identify new genes that may play a role in the highly complex cascade of events
      associated with methamphetamine intoxication. Using Affymetrix oligonucleotide
      arrays, 12 488 genes were simultaneously interrogated and there were 152 whose
      expression levels were changed following methamphetamine treatment. The genes are
      grouped into broad functional categories with inflammatory/immune response
      elements, receptor/signal transduction components and ion channel/transport
      proteins among the most populated. Many genes within these categories can be
      linked to ion regulation and apoptosis, both of which have been implicated in
      methamphetamine toxicity, and numerous factors associated with microglial
      activation emerged with significant changes in expression. For example, brain
      derived neurotrophic factor (BDNF), chemokine (C-C) receptor 6 (CCr6) and
      numerous chemokine transcripts were increased or decreased in expression more
      than 2.8-fold. These results point to activated microglia as a potential source
      of the reactive oxygen/nitrogen species and cytokines that have been previously
      associated with methamphetamine toxicity and other neurotoxic conditions.

PMID- 14690527
TI  - Developmental changes in expression and subcellular localization of the DNA
      repair glycosylase, MYH, in the rat brain.
AB  - Mammalian cells employ a network of DNA repair pathways. DNA repair is required
      during development to ensure accuracy of DNA replication in the rapidly dividing
      embryonic cells and to maintain genomic integrity in the mature organism. An
      enzyme involved in repair of replication errors generated on either normal or
      oxidatively damaged DNA templates, is the mammalian ortholog of the Escherichia
      coli MutY DNA glycosylase (MYH). We show that levels of MYH isoform, detected at
      the E14 embryonic stage, decrease during embryonic and neonatal rat development,
      while new isoforms appear and gradually increase in the neonate and adult brain.
      The temporally declining expression of embryonic MYH resembles the pattern of
      proliferating cell nuclear antigen (PCNA) decline during this period.
      Immunohistochemical analyses of the embryonic brain show that cells staining for
      MYH initially coincide with cells staining for PCNA. At later stages PCNA
      declines, while MYH is detected primarily outside the nucleus. MutY-like
      glycosylase activity for adenines misincorporated opposite oxidized guanines is
      detected in both, embryonic and adult brain extracts. Together, these findings
      suggest that in proliferating embryonic cells, MYH might be primarily involved in
      post replicative repair of nuclear DNA, whereas in post mitotic neurons, in the
      repair of mitochondrial DNA.

PMID- 14690528
TI  - Axonal transport of human alpha-synuclein slows with aging but is not affected by
      familial Parkinson's disease-linked mutations.
AB  - Biochemical and genetic abnormalities of alpha-synuclein (alpha-Syn) are
      implicated in the pathogenesis of Parkinson's disease (PD) and other alpha
      synucleinopathies. The abnormal intraneuronal accumulations of alpha-Syn in Lewy
      bodies (LBs) and Lewy neurites (LNs) have implicated defects in axonal transport
      of alpha-Syn in the alpha-synucleinopathies. Using human (Hu) alpha-Syn
      transgenic (Tg) mice, we have examined whether familial PD (FPD)-linked mutations
      (A30P and A53T) alter axonal transport of Hualpha-Syn. Our studies using
      peripheral nerves show that Hualpha-Syn and Moalpha-Syn are almost exclusively
      transported in the slow component (SC) of axonal transport and that the FPD
      linked alpha-Syn mutations do not have obvious effects on the axonal transport of
      alpha-Syn. Moreover, older pre-symptomatic A53T Hualpha-Syn Tg mice do not show
      gross alterations in the axonal transport of alpha-Syn and other proteins in the
      SC, indicating that the early stages of alpha-synucleinopathy in A53T alpha-Syn
      Tg mice are not associated with gross alterations in the slow axonal transport.
      However, the axonal transport of alpha-Syn slows significantly with aging.
      Because the rate of axonal transport affects the stability and accumulation of
      proteins in axons, age-dependent-slowing alpha-Syn is a likely contributor to
      axonal aggregation of alpha-Syn in alpha-synucleinopathy.

PMID- 14690529
TI  - Tumour necrosis factor alpha inhibits purinergic calcium signalling in blood
      brain barrier endothelial cells.
AB  - The breaching of the blood-brain barrier is an essential aspect in the
      pathogenesis of neuroinflammatory diseases, in which tumour necrosis factor alpha
      (TNF-alpha) as well as endothelial calcium ions play a key role. We investigated
      whether TNF-alpha could influence the communication of calcium signals between
      brain endothelial cells (GP8 and RBE4). Intercellular calcium waves triggered by
      mechanical stimulation or photoliberation of InsP3 in single cells were
      significantly reduced in size after TNF-alpha exposure (1000 U/mL, 2 and 24 h).
      Calcium signals are communicated between cells by means of gap junctional and
      paracrine purinergic signalling. TNF-alpha significantly inhibited gap junctional
      coupling, stimulated the basal release of ATP, and dose-dependently blocked the
      triggered component of ATP release. The cytokine displayed similar effects on the
      uptake of a fluorescent reporter dye into the cells. Previous work with connexin
      mimetic peptides demonstrated that the triggered ATP release in these cells is
      connexin-related; these peptides did, however, not influence the elevated basal
      ATP release caused by TNF-alpha. We conclude that TNF-alpha depresses calcium
      signal communication in blood-brain barrier endothelial cells, by reducing gap
      junctional coupling and by inhibiting triggered ATP release. The cytokine thus
      inhibits connexin-related communication pathways like gap junctions and connexin
      hemichannels.

PMID- 14690530
TI  - Trk is a calmodulin-binding protein: implications for receptor processing.
AB  - The tyrosine kinase receptors for the neurotrophins (Trk) are a family of
      transmembrane receptors that regulate the differentiation and survival of
      different neuronal populations. Neurotrophin binding to Trk leads to the
      activation of several signalling pathways including a rapid, but moderate,
      increase in intracellular calcium levels. We have previously described the role
      of calcium and its sensor protein, calmodulin, in Trk-activated intracellular
      pathways. Here we demonstrate that calmodulin is able to precipitate TrkA from
      PC12 cell lysates. Using recombinant GST-fusion proteins containing the complete
      intracellular domain of TrkA, or fragments of this region, we show that
      calmodulin binds directly to the C-terminal domain of TrkA in a Ca2+-dependent
      manner. We have also co-immunoprecipitated endogenous Trk and calmodulin in
      primary cultures of cortical neurones. Moreover, we provide evidence that
      calmodulin is involved in the regulation of TrkA processing in PC12 cells.
      Calmodulin inhibition results in the generation of a TrkA-derived p41 fragment
      from the cytosolic portion of the protein. This fragment is autophosphorylated in
      tyrosines and can recruit PLCgamma and Shc adaptor proteins. These results
      suggest that calmodulin binding to Trk may be important for the regulation of Trk
      intracellular localization and cleavage.

PMID- 14690531
TI  - Amyloid suppresses induction of genes critical for memory consolidation in APP +
      PS1 transgenic mice.
AB  - Mice transgenic for mutated forms of the amyloid precursor protein (APP) plus
      presenilin-1 (PS1) genes (APP + PS1 mice) gradually develop memory deficits which
      correlate with the extent of amyloid deposition. The expression of several
      immediate-early genes (IEGs: Arc, Nur77 and Zif268) and several other plasticity
      related genes (GluR1, CaMKIIalpha and Na-K- ATPase alphaIII) critical for
      learning and memory was normal in young APP + PS1 mice preceding amyloid
      deposition, but declined as mice grew older and amyloid deposits accumulated.
      Gene repression was less in APP + PS1 mouse brain regions that contain less Abeta
      and in APP mice compared with APP + PS1 mice, further linking the extent of
      amyloid deposition and the extent of gene repression. Critically, we demonstrated
      that amyloid deposition led specifically to impaired induction of the IEGs with
      no effects on basal expression using exposure to a novel environment 30 min prior
      to being killed to induce IEGs. These data imply that Abeta deposition can
      selectively reduce expression of multiple genes linked to synaptic plasticity,
      and provide a molecular basis for memory deficiencies found in transgenic APP
      mice and, most likely, in early stage Alzheimer's disease (AD). Presumably,
      pharmacological agents blocking the Abeta-related inhibition of gene expression
      will have benefit in AD.

PMID- 14690532
TI  - Neurochemical and behavioural changes in zebrafish Danio rerio after systemic
      administration of 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine.
AB  - Dopaminergic deficiency in the brain of zebrafish was produced by systemic
      administration of two catecholaminergic neurotoxins, 6-hydroxydopamine (6-OHDA)
      and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and the neurochemical
      and behavioural changes were characterized. The levels of dopamine and
      noradrenaline decreased significantly after the injection of MPTP and 6-OHDA.
      Corresponding to these changes, fish exhibited characteristic changes in
      locomotor behaviour, i.e. the total distance moved and velocity decreased after
      both neurotoxins. Tyrosine hydroxylase and caspase 3 protein levels were not
      altered after MPTP or 6-OHDA injections, as studied by immunohistochemistry and
      western blotting. The catecholaminergic cell clusters suggested to correspond to
      the mammalian nigrostriatal cell group displayed normal tyrosine hydroxylase
      immunoreactivity after the toxin treatment and did not show signs of DNA
      fragmentation that would indicate activation of cascades that lead to cell death.
      The results show that single systemic injections of MPTP and 6-OHDA induce both
      biochemical and behavioural changes in zebrafish, albeit failing to produce any
      significant morphological alteration in catecholaminergic cell clusters at the
      tested doses. This approach may be used for the screening of chemicals affecting
      the dopaminergic system. The model may be especially useful for evaluation of the
      role of novel genes in neurotoxicity, as a large number of zebrafish mutants are
      becoming available.

PMID- 14690533
TI  - Neuron-glia communication: metallothionein expression is specifically up
      regulated by astrocytes in response to neuronal injury.
AB  - Recent data suggests that metallothioneins (MTs) are major neuroprotective
      proteins within the CNS. In this regard, we have recently demonstrated that MT
      IIA (the major human MT-I/-II isoform) promotes neural recovery following focal
      cortical brain injury. To further investigate the role of MTs in cortical brain
      injury, MT-I/-II expression was examined in several different experimental models
      of cortical neuron injury. While MT-I/-II immunoreactivity was not detectable in
      the uninjured rat neocortex, by 4 days, following a focal cortical brain injury,
      MT-I/-II was found in astrocytes aligned along the injury site. At latter time
      points, astrocytes, at a distance up to several hundred microns from the original
      injury tract, were MT-I/-II immunoreactive. Induced MT-I/-II was found both
      within the cell body and processes. Using a cortical neuron/astrocyte co-culture
      model, we observed a similar MT-I/-II response following in vitro injury.
      Intriguingly, scratch wound injury in pure astrocyte cultures resulted in no
      change in MT-I/-II expression. This suggests that MT induction was specifically
      elicited by neuronal injury. Based upon recent reports indicating that MT-I/-II
      are major neuroprotective proteins within the brain, our results provide further
      evidence that MT-I/-II plays an important role in the cellular response to
      neuronal injury.

PMID- 14690534
TI  - Signalling pathways for insulin-like growth factor type 1-mediated expression of
      uncoupling protein 3.
AB  - Uncoupling protein 3 (UCP3) is a mitochondrial protein with antioxidant
      properties and its regulation by factors promoting cell-survival may be important
      for protection of, for instance, neurons in states of oxidative stress. In the
      present study, we investigated regulatory pathways for UCP3 expression mediated
      by the neuroprotective hormone insulin-like growth factor type 1 (IGF-1) in human
      neuroblastoma SH-SY5Y cells. Northern blot analysis and RT-PCR showed that
      treatment with 10 nm IGF-1 increased the UCP3 mRNA levels 2.5-fold after 5 h. Co
      incubation with the phosphatidylinositol 3 (PI3)-kinase inhibitor LY294002
      prohibited IGF-1-mediated induction of both UCP3 mRNA and protein in a
      concentration-dependent manner, with a complete blockage at 1 microm, as shown by
      RT-PCR and western blot analyses. The mitogen-activated protein (MAP) kinase
      kinase 1 (MKK1 or MEK) inhibitor PD98059 also decreased the UCP3 mRNA expression
      at 10 microm, however, this concentration only partly inhibited the protein
      expression. We conclude that IGF-1 enhanced UCP3 expression at transcriptional
      level, primarily through the PI3-kinase-dependent pathway and partly through the
      MAP kinase pathway.

PMID- 14690535
TI  - CEP11004, a novel inhibitor of the mixed lineage kinases, suppresses apoptotic
      death in dopamine neurons of the substantia nigra induced by 6-hydroxydopamine.
AB  - There is much evidence that the kinase cascade which leads to the phosphorylation
      of c-jun plays an important signaling role in the mediation of programmed cell
      death. We have previously shown that c-jun is phosphorylated in a model of
      induced apoptotic death in dopamine neurons of the substantia nigra in vivo. To
      determine the generality and functional significance of this response, we have
      examined c-jun phosphorylation and the effect on cell death of a novel mixed
      lineage kinase inhibitor, CEP11004, in the 6-hydroxydopamine model of induced
      apoptotic death in dopamine neurons. We found that expression of total c-jun and
      Ser73-phosphorylated c-jun is increased in this model and both colocalize with
      apoptotic morphology. CEP11004 suppresses apoptotic death to levels of 44 and 58%
      of control values at doses of 1.0 and 3.0 mg/kg, respectively. It also
      suppresses, to approximately equal levels, the number of profiles positive for
      the activated form of capase 9. CEP11004 markedly suppresses striatal
      dopaminergic fiber loss in these models, to only 22% of control levels. We
      conclude that c-jun phosphorylation is a general feature of apoptosis in living
      dopamine neurons and that the mixed lineage kinases play a functional role as up
      stream mediators of cell death in these neurons.

PMID- 14690536
TI  - Expression of SOD1 G93A or wild-type SOD1 in primary cultures of astrocytes down
      regulates the glutamate transporter GLT-1: lack of involvement of oxidative
      stress.
AB  - Glutamate excitotoxicity is implicated in the aetiology of amyotrophic lateral
      sclerosis (ALS) with impairment of glutamate transport into astrocytes a possible
      cause of glutamate-induced injury to motor neurons. It is possible that mutations
      of Cu/Zn superoxide dismutase (SOD1), responsible for about 20% of familial ALS,
      down-regulates glutamate transporters via oxidative stress. We transfected
      primary mouse astrocytes to investigate the effect of the FALS-linked mutant
      hSOD1(G93A) and wild-type SOD1 (hSOD1wt) on the glutamate uptake system. Using
      western blotting, immunocytochemistry and RT-PCR it was shown that expression of
      either hSOD1(G93A) or hSOD1wt in astrocytes produced down-regulation of the
      levels of a glutamate transporter GLT-1, without alterations in its mRNA level.
      hSOD1(G93A) or hSOD1wt expression caused a decrease of the monomeric form of GLT
      1 without increasing oxidative multimers of GLT-1. The effects were selective to
      GLT-1, since another glutamate transporter GLAST protein and mRNA levels were not
      altered. Reflecting the decrease in GLT-1 protein, [3H]d-aspartate uptake was
      reduced in cultures expressing hSOD1(G93A) or hSOD1wt. The hSOD1-induced decline
      in GLT-1 protein and [3H]d-aspartate uptake was not blocked by the antioxidant
      Trolox nor potentiated by antioxidant depletion using catalase and glutathione
      peroxidase inhibitors. Measurement of 2',7'-dichlorofluorescein (DCF)-induced
      fluorescence revealed that expression of hSOD1(G93A) or hSOD1wt in astrocytes
      does not lead to detectable increase of intracellular reactive oxygen species.
      This study suggests that levels of GLT-1 protein in astrocytes are reduced
      rapidly by overexpression of hSOD1, and is due to a property shared between the
      wild-type and G93A mutant form, but does not involve the production of
      intracellular oxidative stress.

PMID- 14690537
TI  - Protection by pioglitazone in the MPTP model of Parkinson's disease correlates
      with I kappa B alpha induction and block of NF kappa B and iNOS activation.
AB  - Inflammation has been implicated in the pathogenesis of Parkinson's disease (PD).
      In the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD,
      inducible NO synthase (iNOS) derived nitric oxide (NO) is an important mediator
      of dopaminergic cell death. Ligands of the peroxisome proliferator-activated
      receptor (PPAR) exert anti-inflammatory effects. We here investigated whether
      pioglitazone, a PPARgamma agonist, protected mice from MPTP-induced dopaminergic
      cell loss, glial activation, and loss of catecholamines in the striatum. As shown
      by western blot, PPARgamma was expressed in the striatum and the substantia nigra
      of vehicle- and MPTP-treated mice. Oral administration of 20 mg/(kg day) of
      pioglitazone protected tyrosine hydroxylase (TH)-positive substantia nigra
      neurons from death induced by 5 x 30 mg/kg MPTP. However, the decrease of
      dopamine in the striatum was only partially prevented. In mice treated with
      pioglitazone, there were a reduced activation of microglia, reduced induction of
      iNOS-positive cells and less glial fibrillary acidic protein positive cells in
      both striatum and substantia nigra pars compacta. In addition, treatment with
      pioglitazone almost completely blocked staining of TH-positive neurons for
      nitrotyrosine, a marker of NO-mediated cell damage. Because an increase in
      inhibitory protein-kappa-Balpha (IkappaBalpha) expression and inhibition of
      translocation of the nuclear factor kappaB (NFkappaB) subunit p65 to the nucleus
      in dopaminergic neurons, glial cells and astrocytes correlated with the
      protective effects of pioglitazone, our results suggest that pioglitazone
      sequentially acts through PPARgamma activation, IkappaBalpha induction, block of
      NFkappaB activation, iNOS induction and NO-mediated toxicity. In conclusion,
      treatment with pioglitazone may offer a treatment opportunity in PD to slow the
      progression of disease that is mediated by inflammation.

PMID- 14690538
TI  - Acetylcholine turnover rates in rat brain regions during cocaine self
      administration.
AB  - The involvement of cholinergic neurons in the brain processes underlying
      reinforcement has been recently demonstrated. This experiment assessed the
      potential role of cholinergic neurons in cocaine reinforcement by measuring the
      turnover rates of acetylcholine in brain regions of rats self-administering
      cocaine and in yoked cocaine and yoked vehicle-infused controls. The activity of
      cholinergic innervations of and/or interneurons in the olfactory tubercle,
      caudate putamen, diagonal band-pre-optic region, ventral pallidum, lateral and
      medial hypothalamus, hippocampus, ventral tegmental area and visual cortices
      reflected by the turnover rates of acetylcholine were significantly altered in
      rats self-administering cocaine compared to yoked cocaine infused controls. These
      changes implicate the involvement of cholinergic neurons with cell bodies in the
      diagonal band-pre-optic region, the medial septum and several brainstem nuclei
      and interneurons in the caudate-putamen and ventral pallidum in the processes
      underlying cocaine self-administration. The identified cholinergic neuronal
      systems may have a broader role in the brain processes for natural reinforcers
      (i.e. food, water, etc.) since drugs of abuse are believed to produce reinforcing
      effects through these systems.

PMID- 14690539
TI  - Riboflavin synthase of Schizosaccharomyces pombe. Protein dynamics revealed by
      19F NMR protein perturbation experiments.
AB  - BACKGROUND: Riboflavin synthase catalyzes the transformation of 6,7-dimethyl-8
      ribityllumazine into riboflavin in the last step of the riboflavin biosynthetic
      pathway. Gram-negative bacteria and certain yeasts are unable to incorporate
      riboflavin from the environment and are therefore absolutely dependent on
      endogenous synthesis of the vitamin. Riboflavin synthase is therefore a potential
      target for the development of antiinfective drugs. RESULTS: A cDNA sequence from
      Schizosaccharomyces pombe comprising a hypothetical open reading frame with
      similarity to riboflavin synthase of Escherichia coli was expressed in a
      recombinant E. coli strain. The recombinant protein is a homotrimer of 23 kDa
      subunits as shown by sedimentation equilibrium centrifugation. The protein
      sediments at an apparent velocity of 4.1 S at 20 degrees C. The amino acid
      sequence is characterized by internal sequence similarity indicating two similar
      folding domains per subunit. The enzyme catalyzes the formation of riboflavin
      from 6,7-dimethyl-8-ribityllumazine at a rate of 158 nmol mg(-1) min(-1) with an
      apparent KM of 5.7 microM. 19F NMR protein perturbation experiments using
      fluorine-substituted intermediate analogs show multiple signals indicating that a
      given ligand can be bound in at least 4 different states. 19F NMR signals of
      enzyme-bound intermediate analogs were assigned to ligands bound by the N
      terminal respectively C-terminal folding domain on basis of NMR studies with
      mutant proteins. CONCLUSION: Riboflavin synthase of Schizosaccharomyces pombe is
      a trimer of identical 23-kDa subunits. The primary structure is characterized by
      considerable similarity of the C-terminal and N-terminal parts. Riboflavin
      synthase catalyzes a mechanistically complex dismutation of 6,7-dimethyl-8
      ribityllumazine affording riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H)
      pyrimidinedione. The 19F NMR data suggest large scale dynamic mobility in the
      trimeric protein which may play an important role in the reaction mechanism.

PMID- 14690540
TI  - Hospital care for children and young adults in the last year of life: a
      population-based study.
AB  - BACKGROUND: To help design population-based pediatric palliative care services,
      we sought to describe the hospital care received in the last year of life by
      children and young adults who died. We also determined the proportion with
      complex chronic conditions (CCCs) and tested whether the use of hospital services
      increased as the date of death drew nearer. METHODS: For all deaths occurring
      under 25 years of age from 1990 to 1996 in Washington State, USA, we linked death
      certificate information to hospital utilization records and analyzed the timing
      and duration of hospitalizations and the nature of hospital procedures during the
      year prior to death. RESULTS: Of the 8 893 deaths, 25 % had CCCs. Among infants
      with CCCs, 84 % were hospitalized at the time of death and 50 % had been
      mechanically ventilated during their terminal admission. Among the 458 CCC
      neonates dying under a week of age, 92% of all days of life were spent in the
      hospital; among the 172 CCC neonates dying during the second to fourth weeks of
      life, 85 % of all days of life were spent hospitalized; among the 286 CCC infants
      dying during the second to twelfth month of life, 41 % of all days of life were
      spent hospitalized. Among children and young adults with CCCs, 55 % were
      hospitalized at the time of death, and 19 % had been mechanically ventilated
      during their terminal admission. For these older patients, the median number of
      days spent in the hospital during the year preceding death was 18, yet less than
      a third of this group was hospitalized at any point in time until the last week
      of their lives. The rate of hospital use increased as death drew near. For
      subjects who had received hospital care, 44 % had governmental insurance as the
      source of primary payment. CONCLUSIONS: Infants who died spent a substantial
      proportion of their lives in hospitals, whereas children and adolescents who died
      from CCCs predominantly lived outside of the hospital during the last year of
      life. To serve these patients, pediatric palliative and end-of-life care will
      have to be provided in an integrated, coordinated manner both in hospitals and
      home communities.

PMID- 14690541
TI  - Fibrinogen: a novel predictor of responsiveness in metastatic melanoma patients
      treated with bio-chemotherapy: IMI (italian melanoma inter-group) trial.
AB  - PURPOSE: To evaluate a panel of pretreatment clinical and laboratory parameters
      in metastatic melanoma (MM) in order to verify their impact on response and
      survival in a single prospective multi-institutional phase III study comparing
      out-patient chemotherapy (CT) vs bioCT. METHODS: A total of 176 patients were
      randomised to receive CT (cisplatin, dacarbazine, optional carmustine) or bioCT
      (the same CT followed by subcutaneous IL-2 plus intramuscular alpha-IFN-2b).
      Pretreatment total leucocytes, lymphocytes, eosinophyls, C-reactive protein
      (CRP), lactate dehydrogenase (LDH), erytrosedimentation rate (ESR), and
      fibrinogen were analyzed. Some clinical parameters (performance status, age, sex,
      and disease site) were also considered. As we found a positive trend for bio-CT
      with no statistical significance in OR (25.3% vs 20.2%) and OS (11 Mo vs 9.5 Mo),
      all analyses are stratified by treatment arm. RESULTS: In univariate analysis,
      higher value of lymphocytes percentage (P <.0001), lower value of total
      leucocytes (P=.005), CRP (P=.003), LHD (P <.0001), ESR (P <.027), fibrinogen (P
      <.0001), and no liver disease were strongly related to a better survival. In a
      multivariate analysis, using the Cox proportional hazards model, only fibrinogen
      (P=.004), LDH (P=.009) and liver disease (P=.04) were found to have an
      independent role on clinical outcome in metastatic melanoma patients. CONCLUSION:
      Liver disease and higher LDH and fibrinogen levels had an important impact on
      survival in MM patients. In particular, fibrinogen has been recently reconsidered
      both for its determinant role in the host hemostatic system, and for its
      capability to provide protection against NK and LAK-cell-induced lysis. These
      observations could have some important implications for therapeutic approaches,
      in particular when immunological strategies are used.

PMID- 14690542
TI  - Cervicopectoral flap in head and neck cancer surgery.
AB  - BACKGROUND: Reconstruction of the head and neck after adequate resection of
      primary tumor and neck dissection is a challenge. It should be performed at one
      sitting in advanced tumors. Defects caused by the resection should be closed with
      flaps which match in color, texture and hair bearing characteristics with the
      face. Cervicopectoral flap is a one such flap from chest and neck skin mainly
      used to cover the cheek defects. METHODS: This study included twelve patients
      presenting with cancer of the head and neck to Izmir Ataturk Training Hospital
      and Adnan Menderes University Hospital. Tumor resection and neck dissection was
      performed in one session by the same surgeon. A single incision was made and a
      medially based cervicopectoral fascio-cutaneous flap was used for surgical
      exposure in neck dissection and for closure of defects after tumor resection.
      RESULTS: There was no major complication. Two flaps had partial superficial
      epidermolysis at the suture line. Good aesthetic and functional results were
      achieved. CONCLUSION: The cervicopectoral flap is an excellent alternative for
      the reconstruction of head and neck. Harvesting and application of the flap is
      rapid and safe. Only a single incision is sufficient for dissection and flap
      elevation. This flap achieves perfect surgical exposure, makes neck dissection
      easy and allows one to perform both tumor resection and neck dissection in one
      session.

PMID- 14690543
TI  - Health related quality of life in 3 and 4 year old children and their parents:
      preliminary findings about a new questionnaire.
AB  - BACKGROUND: Few measures of health related quality of life exist for use with
      preschool aged children. The objective of this study was to assess reliability
      and validity of a new multidimensional generic measure of health-related quality
      of life developed for use with preschool children. METHODS: Cross-sectional
      survey sent to parents as their child turned 3 1/2 years of age. The setting was
      the province of British Columbia, Canada. Patients included all babies admitted
      to tertiary level neonatal intensive care units (NICU) at birth over a 16-month
      period, and a consecutive sample of healthy babies. The main outcome measure was
      a new full-length questionnaire consisting of 3 global items and 10 multi-item
      scales constructed to measure the physical and emotional well-being of toddlers
      and their families. RESULTS: The response rate was 67.9%. 91% (NICU) and 84%
      (healthy baby) of items correlated with their own domain above the recommended
      standard (0.40). 97% (NICU) and 87% (healthy baby) of items correlated more
      highly (> or = 2 S.E.) with their hypothesized scale than with other scales.
      Cronbach's alpha coefficients varied between.80 and.96. Intra-class correlation
      coefficients were above.70. Correlations between scales in the new measure and
      other instruments were moderate to large, and were stronger than between non
      related domains. Statistically significant differences in scale scores were
      observed between the NICU and healthy baby samples, as well as between those
      diagnosed with a health problem requiring medical attention in the past year
      versus those with no health problems. CONCLUSIONS: Preliminary results indicate
      the new measure demonstrates acceptable reliability and construct validity in a
      sample of children requiring NICU care and a sample of healthy children. However,
      further development work is warranted.

PMID- 14690544
TI  - Bending out and breaking away: host-cell accomplices in retroviral escape.
AB  - Budding through the host-cell membrane is a key step in the life cycle of many
      viruses. Recent studies of retrovirus replication implicate a large number of
      cellular proteins in this process.

PMID- 14690545
TI  - Budding viral hijackers co-opt the endocytic machinery to make a getaway.

PMID- 14690546
TI  - High levels of tissue plasminogen activator (tPA) antigen precede the development
      of type 2 diabetes in a longitudinal population study. The Northern Sweden MONICA
      study.
AB  - BACKGROUND: Impaired fibrinolysis is found in impaired glucose tolerance and type
      2 diabetes, associated with components of the metabolic syndrome. There are no
      data concerning fibrinolysis in subjects with normal glucose tolerance that
      convert to diabetes. METHODS: We studied the activities of tissue plasminogen
      activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) and the levels of
      tPA antigen (a marker of endothelial dysfunction) in 551 subjects with normal
      glucose tolerance in 1990 in relation to incident diabetes during nine years of
      follow-up. RESULTS: Subjects with diabetes at follow-up (n = 15) had
      significantly lower baseline tPA activity and higher PAI-1 activity and tPA
      antigen than non-converters. The risk of diabetes increased linearly across
      quartiles of PAI-activity (p = 0.007) and tPA antigen (p < 0.001) and decreased
      across quartiles of tPA activity (p = 0.026). The risk of diabetes with low tPA
      activity or high PAI-1 activity persisted after adjustment for age and sex but
      diminished to a non-significant level after further adjustments. The odds ratio
      of diabetes for high tPA antigen was 10.4 (95% confidence interval 2.7-40)
      adjusted for age and sex. After further adjustment for diastolic blood pressure,
      waist circumference, insulin, triglycerides, fasting and post load glucose the
      odds ratio was 6.5 (1.3-33, p = 0.024). CONCLUSIONS: Impaired fibrinolysis and
      endothelial dysfunction are evident in subjects with normal glucose tolerance who
      later develop diabetes. High tPA antigen is predictive of future diabetes
      independent from the metabolic syndrome.

PMID- 14690547
TI  - Clinical psychoacoustics in Alzheimer's disease central auditory processing
      disorders and speech deterioration.
AB  - BACKGROUND: Difficulty in speech understanding in the presence of background
      noise or competing auditory signals is typically present in central auditory
      processing disorders. These disorders may be diagnosed in Alzheimer's disease as
      a result of degeneration in the central auditory system. In addition perception
      and processing of speech may be affected. MATERIAL AND METHODS: A MEDLINE
      research was conducted in order to answer the question whether there is a central
      auditory processing disorder involved in Alzheimer's disease. A second question
      to be investigated was what, if any is the connection, between central auditory
      processing disorders and speech deterioration?Articles were retrieved from the
      Medline to find relevance of Alzheimer's dis ease with central auditory
      processing disorders, they summed up to 34. Twelve papers were studied that
      contained testing for CAPD through psychoacoustic investigation. An additional
      search using the keywords 'speech production' and 'AD' produced a result of 33
      articles, of them 14 are thoroughly discussed in this review as they have
      references concerning CAPD. The rest do not contain any relavent information on
      the central auditory system. RESULTS: Psychoacoustic tests reveal significantly
      lower scores in patients with Alzheimer's disease compared with normal subjects.
      Tests concerning sound localization and perception of tones as well as phoneme
      discrimination and tonal memory reveal deficits in Alzheimer's disease. Central
      auditory processing disorders may exist several years before the onset of
      clinical diagnosis of Alzheimer's disease. Segmental characteristics of speech
      are normal. Deficits exist concerning the supra-segmental components of speech.
      CONCLUSIONS: Central auditory processing disorders have been found in many cases
      when patients with Alzheimer's disease are tested. They may present as an early
      manifestation of Alzheimer's disease, preceding the disease by a minimum of 5 and
      a maximum of 10 years. During these years changes in the central auditory system,
      starting in the temporal lobe, may produce deficits in speech processing and
      production as hearing and speech are highly connected human functions. Another
      theory may be that spread of degeneration of the central nervous system has as a
      consequence, speech deterioration. Further research and central auditory
      processing disorders testing in the elderly population are needed to validate one
      theory over the other.

PMID- 14690548
TI  - Circulating soluble Fas levels and risk of ovarian cancer.
AB  - BACKGROUND: Dysregulation of apoptosis, specifically overexpression of soluble
      Fas (sFas), has been proposed to play a role in the development of ovarian
      cancer. The main objective of the present study was to evaluate serum sFas as a
      potential biomarker of ovarian cancer risk. METHODS: The association between
      serum sFas levels and the risk of ovarian cancer was examined in a case-control
      study nested within three prospective cohorts in New York (USA), Umea (Sweden),
      and Milan (Italy). Case subjects were 138 women with primary invasive epithelial
      ovarian cancer diagnosed between 2 months and 13.2 years after the initial blood
      donation. Control subjects were 263 women who were free of cancer, and matched
      the case on cohort, menopausal status, age, and enrollment date. Serum sFas
      levels were determined using a quantitative sandwich enzyme immunoassay. RESULTS:
      Serum sFas levels were similar in women subsequently diagnosed with ovarian
      cancer (median, 6.5 ng/mL; range, 4.4-10.2) and in controls (median, 6.8 ng/mL;
      range, 4.5-10.1). Statistically significant trends of increasing serum sFas with
      age were observed among cases (r = 0.39, p < 0.0001) and controls (r = 0.42, p <
      0.0001). Compared to women in the lowest third, women in the highest third of
      serum sFas were not at increased risk of ovarian cancer after adjustment for
      potential confounders (odd ratio (OR), 0.87; 95% confidence interval (CI), 0.42
      1.82). CONCLUSION: The results suggest that serum sFas may not be a suitable
      marker for identification of women at increased risk of ovarian cancer.

PMID- 14690549
TI  - Medication-related problem type and appearance rate in ambulatory hemodialysis
      patients.
AB  - BACKGROUND: Hemodialysis (HD) patients are at risk for medication-related
      problems (MRP). The MRP number, type, and appearance rate over time in ambulatory
      HD patients has not been investigated. METHODS: Randomly selected HD patients
      were enrolled to receive monthly pharmaceutical care visits. At each visit, MRP
      were identified through review of the patient chart, electronic medical record,
      patient interview, and communications with other healthcare disciplines. All MRP
      were categorized by type and medication class. MRP appearance rate was determined
      as the number of MRP identified per month/number of months in study. The number
      of MRP per patient-drug exposures were determined using: [[(number of patients) x
      (mean number of medications)]/(number of months of study)] /number of MRP
      identified. Results were expressed as mean +/- standard deviation or percentages.
      RESULTS: Patients were 62.6 +/- 15.9 years old, had 6.4 +/- 2.0 comorbid
      conditions, were taking 12.5 +/- 4.2 medications, and 15.7 +/- 7.2 doses per day
      at baseline. Medication-dosing problems (33.5%), adverse drug reactions (20.7%),
      and an indication that was not currently being treated (13.5%) were the most
      common MRP. 5,373 medication orders were reviewed and a MRP was identified every
      15.2 medication exposures. Overall MRP appearance rate was 0.68 +/- 0.46 per
      patient per month. CONCLUSION: MRP continue to occur at a high rate in ambulatory
      HD patients. Healthcare providers taking care of HD patients should be aware of
      this problem and efforts to avoid or resolve MRP should be undertaken at all HD
      clinics.

PMID- 14690550
TI  - Pragmatic controlled clinical trials in primary care: the struggle between
      external and internal validity.
AB  - BACKGROUND: Controlled clinical trials of health care interventions are either
      explanatory or pragmatic. Explanatory trials test whether an intervention is
      efficacious; that is, whether it can have a beneficial effect in an ideal
      situation. Pragmatic trials measure effectiveness; they measure the degree of
      beneficial effect in real clinical practice. In pragmatic trials, a balance
      between external validity (generalizability of the results) and internal validity
      (reliability or accuracy of the results) needs to be achieved. The explanatory
      trial seeks to maximize the internal validity by assuring rigorous control of all
      variables other than the intervention. The pragmatic trial seeks to maximize
      external validity to ensure that the results can be generalized. However the
      danger of pragmatic trials is that internal validity may be overly compromised in
      the effort to ensure generalizability. We are conducting two pragmatic randomized
      controlled trials on interventions in the management of hypertension in primary
      care. We describe the design of the trials and the steps taken to deal with the
      competing demands of external and internal validity. DISCUSSION: External
      validity is maximized by having few exclusion criteria and by allowing
      flexibility in the interpretation of the intervention and in management
      decisions. Internal validity is maximized by decreasing contamination bias
      through cluster randomization, and decreasing observer and assessment bias, in
      these non-blinded trials, through baseline data collection prior to
      randomization, automating the outcomes assessment with 24 hour ambulatory blood
      pressure monitors, and blinding the data analysis. SUMMARY: Clinical trials
      conducted in community practices present investigators with difficult
      methodological choices related to maintaining a balance between internal validity
      (reliability of the results) and external validity (generalizability). The
      attempt to achieve methodological purity can result in clinically meaningless
      results, while attempting to achieve full generalizability can result in invalid
      and unreliable results. Achieving a creative tension between the two is crucial.

PMID- 14690552
TI  - [Correlation between the expression of collgen IV, VEGF and vasculogenic
      mimicry].
AB  - OBJECTIVE: To study the relationship between collgen (Col) IV, VEGF secreted by
      the tumor cells and vasculogenic mimicry (VM). METHODS: 158 bi-phase differential
      malignant tumor specimens were alloted and made into tissue microarray. These
      tissue microarray sections were stained with CD31, periodic acid-Schiff (PAS) and
      Col IV. Subsequently, distributive trait of Col IV and the difference of VEGF
      expression were analyzed. RESULTS: The basement membrane of VM was PAS and Col IV
      positive. The expression of VEGF in bi-phase differential malignant tumor with VM
      was less than that in those without VM. The difference of VEGF expression in
      malignant melanoma and alveolar rhabdomyosarcoma was significant (P < 0.05).
      CONCLUSION: Collgen IV and periodic acid-Schiff positive material take part in
      constructing the basement membrane of vasculogenic mimicry. The difference of the
      VEGF expression proves that vasculogenic mimicry can sustain the tumor blood
      supply.

PMID- 14690551
TI  - Statistical extraction of Drosophila cis-regulatory modules using exhaustive
      assessment of local word frequency.
AB  - BACKGROUND: Transcription regulatory regions in higher eukaryotes are often
      represented by cis-regulatory modules (CRM) and are responsible for the formation
      of specific spatial and temporal gene expression patterns. These extended,
      approximately 1 KB, regions are found far from coding sequences and cannot be
      extracted from genome on the basis of their relative position to the coding
      regions. RESULTS: To explore the feasibility of CRM extraction from a genome, we
      generated an original training set, containing annotated sequence data for most
      of the known developmental CRMs from Drosophila. Based on this set of
      experimental data, we developed a strategy for statistical extraction of cis
      regulatory modules from the genome, using exhaustive analysis of local word
      frequency (LWF). To assess the performance of our analysis, we measured the
      correlation between predictions generated by the LWF algorithm and the
      distribution of conserved non-coding regions in a number of Drosophila
      developmental genes. CONCLUSIONS: In most of the cases tested, we observed high
      correlation (up to 0.6-0.8, measured on the entire gene locus) between the two
      independent techniques. We discuss computational strategies available for
      extraction of Drosophila CRMs and possible extensions of these methods.

PMID- 14690553
TI  - [Inhibitory effect of p53 with deletion of c-terminal 356 - 393 amino acids on
      malignant phenotype of human lung cancer cell line].
AB  - OBJECTIVE: To study the effect of extraneous p53 gene with deletion of c-terminal
      356 - 393 amino acids on inhibition of malignant phenotype of human lung cancer
      cell line. METHODS: Recombinant plasmid pEGFP-p53 (del) with codon deletion of c
      terminal 37 amino acids from 393 to 356 region and pEGFP-p53 (wild type) were
      constructed. The human lung cancer cell line 801D served as a receipt cell had
      p53 deletion and mutation at 248 codon. 801D cells, having been transfected by
      pEGFP-p53 (wild type), pEGFP-p53 (del) or pEGFP, were selected by G418. Growing
      transfected cells were cloned respectively by method of dilution. Presence of
      extraneous gene was detected by PCR, their expression in cells was examined by
      fluorescence microscopy. Cloning efficiency was in vitro tested to examine the
      cellular proliferating ability. The xenograft in nude mice was performed and
      xenograft tumors were weighed one month later. Expression of GFP in tumor and
      transplanted cellular mass were detected by blot slices. RESULTS: pEGFP-p53 (del)
      801D, pEGFP-p53-801D and pEGFP-801D were established. Extraneous p53 gene and
      expression of GFP were found in pEGFP-p53 (del)-801D and pEGFP-p53-801D.
      Inhibitory rate of colony was 99.6% for pEGFP-p53 (del)-801D and 81.0% for pEGFP
      p53-801D. Inhibition of malignant proliferation of extraneous p53 (del) was
      higher than that of p53 (wild type) (P < 0.01). Even when inhibition of malignant
      proliferation extraneous pEGFP-p53 (del) was obvious, 0.2% colonies were formed,
      extraneous p53 and expression of GFP were observed. Animal test showed that tumor
      on the nude mice was positive (4/4, 4/4) in the control group (801D and pEGFP
      801D), but negative (0/4, 0/4) in the experiment group [pEGFP-p53 (del) 801D and
      pEGFP-p53 (wild type) 801D]. Expression of GFP in the cells of cellular mass
      transplanted by pEGFP-p53 (del) 801D or pEGFP-p53 (wild type) 801D was observed.
      CONCLUSION: In vitro inhibitory effect of extraneous p53 gene with deletion of C
      terminal 356 - 393 amino acids on malignant growth of lung cancer cell with p53
      mutation or deletion at 248 codon is marked. Inhibitory action of p53 on
      malignant proliferation of cancer cells is heterogeneous.

PMID- 14690554
TI  - [Study on differentially expressed molecules influencing the metastatic potential
      between highly and poorly metastatic human lung giant cell carcinoma].
AB  - OBJECTIVE: To study the metastasis-associated molecules differentially expressed
      in highly and poorly metastatic sublines and the mechanism of metastasis in lung
      giant cell carcinoma. METHODS: Highly and poorly metastatic sublines (PLA801D and
      PLA801C)were used as metastasis model. Cell motility and invasion assay in vitro
      were first compared between the two sublines. Then, gelatin zymography analysis
      was used to determine the MMP-2 and MMP-9 activity. The protein expression level
      of secreted MMP-2, MMP-9, TIMP-1, TIMP-2 and intracellular expression level of
      p53, p16, PCNA, CD44(V6) isomeride, E-cadherin, CK18, nm23-H1 as well as the mRNA
      expression level of MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF were compared through
      Western blot. Semi-quantitative RT-PCR analysis was used to determine the
      intracellular mRNA expression of MMP-2, MMP-9, TIMP-1, TIMP-2 and VEGF. RESULTS:
      The in vitro cell invasion potential of highly metastatic subline PLA801D was
      significantly higher than that of poorly metastatic subline PLA801C by about 4
      folds, while the cell motility potential was similar. The secreted MMP-2 activity
      was notably higher in PLA801D, which was initiated by the higher expression of
      MMP-2 at protein and mRNA level. In addition, the expression level of p53, PCNA,
      CK18 protein and VEGF mRNA were significantly higher, while the expression level
      of p16, E-cadherin and nm23-H1 protein were significantly lower in PLA801D. Some
      molecules such as MMP-9, TIMP-1, TIMP-2, CD44(V6) isomeride, which had been
      reported to be associated with tumor metastasis, were not observed to change
      significantly between the two sublines. CONCLUSION: There are significant
      differences in metastatic potential and phenotypes between highly and poorly
      metastatic sublines of lung giant cell carcinoma. Some differentially expressed
      molecules might be playing roles in promoting or inhibiting metastasis of lung
      giant cell carcinoma, which may be useful to elucidate the mechanism of
      metastasis.

PMID- 14690555
TI  - [Heterogeneity of human breast cancer cells and their biological behavior].
AB  - OBJECTIVE: To investigate the heterogeneity of human breast cancer cells, their
      influence on biological behavior of tumor cells and clinical implications.
      METHODS: The subpopulations of MCF-7 breast cancer cells were isolated by Percoll
      gradient centrifugation. DNA content and cell cycle distribution were detected
      with flow cytometry. Tumor chemosensitivity analysis was performed with MTT
      assay. RESULTS: Heterogeneity was observed in DNA content and cell cycle
      distribution among four subpopulations of breast cancer cells, which were related
      to their proliferation ability and chemosensitivity results. CONCLUSION:
      Hereditary instability and intrinsic characteristics of most tumor cells, not
      only lead to tumor progression and heterogeneity but also cause the loss of
      monoclonality and the generation of subclones. Further study on some profiles of
      tumor heterogeneity such as DNA content, cell cycle distribution and their
      influence on tumor proliferation and chemosensitivity may very well improve the
      clinical treatment.

PMID- 14690556
TI  - [Antisense DNMT1 gene fragment in the sensitivity change of SMMC-7721 cells to
      tumor necrosis factor related apoptosis inducing ligand and its mechanism].
AB  - OBJECTIVE: To observe the sensitivity change of SMMC-7721 cells transfected with
      antisense DNMT1 gene fragment to tumor necrosis factor related apoptosis inducing
      ligand (TRAIL) and its mechanism. METHODS: Cell survival rate was measured by
      trypan blue, apoptosis rate by TUNEL method and the expression of bcl-2, bax and
      bad by flow cytometry. RESULTS: Cell survival rate of SMMC-7721 cells transfected
      with antisense DNMT1 gene fragment was markedly lower than that transfected with
      sense DNMT1 gene fragment or empty vector (P < 0.05 and 0.01), but the apoptosis
      rate was on the contrary (P < 0.05 or 0.01). The expression of bax and bad
      (especially the former), but not bcl-2 of SMMC-7721 cells transfected with
      antisense DNMT1 gene fragment was markedly higher than those of SMMC-7721 cells
      transfected with sense DNMT1 gene fragment or empty vector. CONCLUSION: The
      sensitivity of SMMC-7721 cells to TRAIL can be enhanced by the transfection of
      antisense DNMT1 gene fragment, which may be related to the increase of bax and
      bad expression.

PMID- 14690557
TI  - [Contribution of eukaryotic initiation factor-4E inhibition to heparanase
      expression and activity in human colon adenocarcinoma cell line LS-174T].
AB  - OBJECTIVE: To determine whether the eukaryotic initiation factor-4E (eIF-4E) is
      involved in the cap-dependent translational regulation of heparanase and study
      the correlation between heparanase expression and metastatic potential of LS-174T
      cells. METHODS: The protein and mRNA levels of inhibited eIF-4E were tested by
      Western blot and RT-PCR. Heparanase activity was defined as the ability to
      degrade high molecular weight (40-100 000) radiolabeled ((35)S) heparan sulfate
      (HS) substrate into low molecular weight (5-15 000) HS fragments. The invasive
      potential of tumor cells in vitro was observed by Matrigel invasion assay system.
      RESULTS: The 20-mer antisense oligonucleotide (asODN) against eIF-4E specifically
      and significantly inhibited eIF-4E expression at both transcriptional and
      translational levels. The expression and the activity of heparanase were
      effectively lowered, which further decreased the invasive potential of LS-174T.
      CONCLUSION: eIF-4E, probably being involved in translational regulation of
      heparanase in colon adenocarcinoma cell line LS-174T, can be a particularly
      interesting target for heparanase regulation, based on of its critical function.

PMID- 14690558
TI  - [Effect of hepatic artery embolization on the microwave coagulated area].
AB  - OBJECTIVE: To study the effect of hepatic artery embolization on the microwave
      coagulated area, an in vivo animal experiment. METHODS: Twenty-four suitable
      hepatic lobes of ten dogs were divided into two groups: microwave coagulation
      alone 12 lobes (control group) and hepatic artery occlusion with iodized oil and
      gelatin sponge particles followed by microwave coagulation 12 (experiment group).
      Microwave coagulation was delivered with an output of 50 W for 300 or 400 seconds
      with thermal needles introduced parallel to and 5 approximately 20 mm from the
      puncture needle. After sacrifice of the dogs, their hepatic lobes were sectioned
      along the puncture line. Then, the appearance and size of the coagulated area
      were recorded. The tissue specimens were fixed in formalin for light microscopic
      evaluation. RESULTS: A decline in temperature gradient was detected from the
      center to the periphery of the affected tissue after the application of microwave
      coagulation, which was sharper in the control group than in the experimental
      group. Single polar microwave coagulation at 50 W for 300 seconds produced a
      necrotic volume of 25 approximately 33 mm in longitudinal diameter and 13
      approximately 22 mm in transverse diameter in control group, 33 approximately 44
      mm and 24 approximately 32 mm in the experimental group. The coagulation area was
      slightly bigger when the duration of coagulation was 400 seconds than 300
      seconds, without significant difference. CONCLUSION: Hepatic artery occlusion,
      inhibiting the heat loss caused by hepatic arterial blood flow, is able to
      significantly enlarge the necrotic volume of microwave coagulation.

PMID- 14690559
TI  - [Melatonin in in vitro apoptosis of H22 hepatocarcinoma cells].
AB  - OBJECTIVE: To study the effect of melatonin (MLT) in in vitro apoptosis of
      hepatocarcinoma cells and its mechanism. METHODS: The apoptotic cells, bcl-2 and
      bax were detected through immunocytochemical method (ICC) and Tolt-mediated x
      duTP nick end labeling (TUNEL). Computer image analysis system was used to
      quantify the expression of bcl-2 and bax by detecting the absorbance value of
      positive products. Apoptosis index (AI) was used to quantify the number of
      apoptotic cells. RESULTS: In vitro, AI increase was both concentration- and time
      dependent through TUNEL. During the same duration, AI of medium dose group was
      higher than that of low dose and control group (P < 0.05); AI of high dose,
      medium dose and 5-Fu group were higher than those of low dose and control group
      (P < 0.01), however, there was no significant difference between the low dose and
      control group (P > 0.05). At the same dose, in high dose, medium dose and 5-Fu
      group, the change of AI showed significant difference from 24 to 36 hours (P <
      0.05). The expression of bcl-2 was down-regulated as the MLT increased, and there
      was significant difference between the low dose and control group (P < 0.01).
      But, the expression of bax was up-regulated as the dose of MLT increased, showing
      significant difference between the high dose and control groups (P < 0.01). As
      time went on, the expression of bcl-2 was decreased and in every group, with the
      change in absorbance value of bcl-2 significantly different from 24 to 36 hours
      (P < 0.05), whereas that of bax remained almost unchanged. The ratio of bax/bcl-2
      was increased with the increase in the concentration of MLT. CONCLUSION:
      Melatonin may induce apoptosis in the hepatocarcinoma cells which is
      concentration- and time-dependent, in which bcl-2 and bax are involved.

PMID- 14690560
TI  - [Poly(AT) polymorphism in DNA repair gene XPC and lung cancer risk].
AB  - OBJECTIVE: It has been shown that suboptimal DNA repair capacity is associated
      with cancer risk and that a poly(AT) polymorphism in XPC gene (XPC PAT) may
      influence DNA capacity. This study was designed to assess the relationship
      between XPC PAT polymorphism and susceptibility to lung cancer in the Chinese
      population. METHODS: XPC genotypes were determined by PCR methods in 509 healthy
      controls and 597 patients with lung cancer. The adjusted odds ratios (ORs) and
      95% confidence intervals (CIs) were calculated using multivariate logistic
      regression model. RESULTS: Genotype frequencies of XPC PAT among controls were
      37.9% (PAT-/-), 49.7% (PAT+/-) and 12.4% (PAT+/+), respectively. They were not
      significantly different from those among lung cancer patients (42.1%, 46.7% and
      11.2%, respectively; P = 0.37). Individuals carrying XPC PAT+/+ genotype were not
      at increased risk for lung cancer as compared with those with PAT+/- or PAT-/-
      genotype (adjusted OR, 0.8; 95% CI, 0.55 approximately 1.16). No interaction
      between XPC genotype and smoking was observed. CONCLUSION: Our findings indicate
      that the XPC PAT polymorphism may not be associated with risk of lung cancer in
      the Chinese population.

PMID- 14690561
TI  - [Effect of p53 expression in the primary lesion and the surgical margin on the
      postoperative radiotherapy for laryngeal squamous carcinoma].
AB  - OBJECTIVE: To analyze the correlation between prognosis and p53 expression in
      primary lesion and the surgical margin of laryngeal squamous cell carcinoma (SCC)
      as an indication of postoperative radiotherapy. METHODS: Sixty-seven laryngeal
      SCC with pathological negative margin were analyzed retrospectively.
      Immunohistochemical method was used to detect the expression of p53. RESULTS: The
      p53 positive rates in the primary tumor and the surgical margin were 19.4%
      (13/67) and 50.7% (34/67). In p53 positive primary tumor group, the survival rate
      was higher in patients who received postoperative radiotherapy than those without
      (60.6% vs 20.0%, P = 0.000 5) and the recurrent rate was just the reverse (42.1%
      vs 93.3%, P = 0.002), though these differences were not significant in p53
      negative primary tumor group (87.5% vs 94.1%, P = 0.409 6; 25.0% vs 5.9%, P =
      0.175). The recurrent rate and survival rate between patients with and without
      postoperative radiotherapy did not show any significant difference either in p53
      positive surgical margin group (47.4% vs 20.0%, P = 0.378 1; 62.5% vs 80.0%, P =
      1.0) or p53 negative ones (84.9% vs 66.6%, P = 0.074 3; 20.6% vs 40.7%, P =
      0.248). CONCLUSION: Postoperative radiotherapy should be given to patients with
      p53 positive primary laryngeal cancer. But those who are pathologically margin
      negative but p53 positive should not be taken, at least for the present, as
      candidates for postoperative radiotherapy.

PMID- 14690562
TI  - [Relation between vascular endothelial growth factor and reoccurence-metastasis
      after transcatheter arterial chemoembolization in hepatocellar carcinoma].
AB  - OBJECTIVE: To investigate the relation between changes in serum vascular
      endothelial growth factor (VEGF) level after transcatheter arterial
      chemoembolization (TACE) and hepatocellular carcinoma (HCC) progression,
      especially in relation to metastasis. METHODS: Serum VEGF expression level,
      measured by quatitative sandwich enzyme-linked immunosorbent assay (ELISA, R&D
      system), was measured before, 3 days and 4 weeks after TACE in 30 patients with
      HCC. The development of metastasis was evaluated at the end of the third month
      after TACE. RESULTS: 1. The serum VEGF level in 30 patients was 154.47 +/- 90.17
      pg/ml, 2. Post-TACE total serum VEGF level increased as compared with their basal
      level in 30 patients (P < 0.05) and serum VEGF level had a tendency to increase
      in patients with heterogeneous uptake of iodized oil and portal vein thrombosis.
      During the follow-up of 1 - 2 years, metastatic foci were found in 74% (20)
      patients with SVEGF increase, while none of the patients showing SVEGF decrease
      developed metastasis. CONCLUSION: Serum VEGF expression increase is associated
      with the development of metastasis in hepatocellular carcinoma after TACE.

PMID- 14690563
TI  - [A comparative study on radiology and pathology target volume in non-small-cell
      lung cancer].
AB  - OBJECTIVE: Defining the margin of clinical target volume (CTV) is very important
      for three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated
      radiation therapy (IMRT). In this study, according to the comparison between
      gross tumor volume (GTV) silhouetted by radiology and pathology in non-small-cell
      lung cancer (NSCLC), we tried to define the correlation of GTV by radiology and
      pathology, and assess the degree of correlation to local microscopic extension
      (ME) among different pathologic types of NSCLC, so as to define the margin of CTV
      precisely. METHODS: From February 2001 to February 2002, forty-three NSCLC
      patients after surgical resection were studied. All patients had had CT scans of
      the chest before surgery and routine pathology examination after surgery. The
      tumor size at X (lateral direction), Y (ventrodorsal direction) and Z
      (craniocaudal direction) axes were measured on CT. Also by pathology examination,
      the tumor size at X, Y, Z axes and the degree of ME at X, Y, Z axes were
      measured, respectively. RESULTS: Without taking into account the value of ME,
      there was almost total agreement on the GTV by radiology and pathology in three
      dimensions. The mean value of ME was 2.18 mm for adenocarcinoma (ADC) and 1.33 mm
      for squamous cell carcinoma (SCC) (P = 0.001). But, taking into account 95% of
      the ME, a margin of 7 mm and 5 mm must be allowed for ADC and SCC, respectively.
      CONCLUSION: There exists a correlation of GTV by radiology and pathology. In the
      target volume defining for 3DCRT and IMRT, we could use the GTV by radiology
      instead of the GTV by pathology, with the ME being different for ADC and SCC. To
      cover 95% of the ME, the margin from GTV to CTV must be extended to 7 mm and 5 mm
      for ADC and SCC, respectively.

PMID- 14690564
TI  - [Relationship between early enhanced helical CT and tumor angiogenesis in bladder
      cancer].
AB  - OBJECTIVE: To study the relationship between enhanced degree in the cancer lesion
      and angiogenesis in the tumor through early manifestations in enhanced helical CT
      in patients with bladder cancer. METHODS: Fifty-three patients with bladder
      carcinoma were examined by pelvic plain CT and helical CT scan at peak
      enhancement of cancer lesion. Histologic grade, vascular endothelial growth
      factor (VEGF) and micro-vascular density (MVD) were analyzed for each resected
      cancer lesion. Pearson and Spearman correlation tests were used to assess the
      relationship between CT enhancement and histologic grade, VEGF or MVD. RESULTS:
      In early enhancing phase of helical CT, different degrees of enhancement were
      observed in 73 bladder cancer lesions. The difference between average CT
      attenuation and MVD in different histologic grade cancer lesions was
      statistically significant (P < 0.001). A positive correlation was found between
      the CT enhancement and MVD (gamma = 0.936, P < 0.001), histologic grade (gamma =
      0.75, P < 0.001), but VEGF of bladder cancer did not correlate with the CT
      enhancement or MVD. CONCLUSION: The early enhancement of helical CT enhancement
      of bladder cancer, showing a positive relation to MVD and histologic grade, can
      reflect the tumor angiogenesis and blood supply.

PMID- 14690565
TI  - [Serum her-2/neu level and related factors in patients with breast cancer].
AB  - OBJECTIVE: To detect serum her-2/neu level in patients with breast cancer of
      different stages and its relationship with tissue her-2/neu overexpression as
      well as other factors. METHODS: A total of 120 women were alloted in this study,
      including 10 healthy volunteers, 31 breast benign disease patients, 53 primary
      breast cancer and 26 metastatic breast cancer patients. The level of serum her
      2/neu was detected with enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Elevated serum her-2/neu levels were observed in 0/10 healthy volunteers, 0/31
      patients with benign tumor and 10/53 (18.9%) operable breast cancer patients.
      Serum concentration of soluble her-2/neu was correlated with tumor size (P <
      0.05), but not with axillary lymph nodes nor estrogen receptor status. In
      patients with metastatic disease, soluble her-2/neu serum level was elevated in
      61.5% (16/26) of patients, which was not correlated with the site of metastasis
      (P > 0.05). CONCLUSION: Serum her-2/neu level is correlated with tumor
      malignancy, stage and cancer load. It could be helpful in directing the treatment
      of recurrent or metastatic breast cancer.

PMID- 14690566
TI  - [Risk factors of lung cancer in Tianjin].
AB  - OBJECTIVE: To investigate the risk factors of lung cancer in Tianjin and to
      provide evidence for further monitor there of. METHODS: A case-control study
      involving interviews with 193 new cases and 259 controls aged 30 - 76 years was
      carried out. Structured questionnaires were used to collect information on
      general condition, living environment, living style, disease and family history,
      etc. Logistic regression model univariate and multivariate analysis were used to
      pick out the significant lung cancer risk factors. RESULTS: By monovariate
      analysis, risk factors such as smoking, passive smoking, drinking, history of
      malignancy in family and occupation were found. By multivariate analysis,
      smoking, passive smoking, higher body mass index (BMI) and average income and
      living space per capita ten years earlier were ascertained, their operations
      research (OR) values were 3.302, 1.193, 1.003, 1.067 and 0.913. CONCLUSION:
      Smoking and passive smoking are independent risk factors of lung cancer. Monthly
      income per person and living space per person 10 years earlier are associated
      with elevated risk of lung cancer. Higher body mass index has protective effects
      on lung cancer risk.

PMID- 14690567
TI  - [Result of phase II clinical trial of herceptin in advanced Chinese breast cancer
      patients].
AB  - OBJECTIVE: To observe the clinical efficacy and adverse effects of herceptin for
      advanced Chinese breast cancer patients. METHODS: Thirty-one pathologically
      proved advanced breast cancer women were treated by herceptin. In the first week,
      a loading dose 4 mg/kg was administered by intravenous infusion and from the
      second week, a routine dose of 2 mg/kg was given every week for at least 3
      months. RESULTS: There were 2 CR, 6 PR, 7 SD, and 16 PD among 31 patients after
      treatment by herceptin, the response rate being 25.8%. In factors influencing the
      prognosis, age and general condition were factors favoring the results, and
      pathological type, site of metastasis, grade of her-2 over expression and prior
      treatment were irrelevant to the results. The adverse effects were mild but
      different from those of the common anticancer drugs. CONCLUSION: Herceptin is
      effective and well tolerated by the Chinese breast cancer patients.

PMID- 14690569
TI  - [Vinorelbine plus cisplatin in the treatment of advanced non-small cell lung
      cancer previously treated with taxane-based chemotherapy].
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of vinorelbine plus cisplatin in
      the treatment of advanced non-small cell lung cancer (NSCLC) previously treated
      with taxane-based chemotherapy. METHODS: Thirty patients (0 - 1 score ECOG
      performance status) with stage IIIB/IV NSCLC previously treated with taxane-based
      chemotherapy were eligible for the study. Fifteen patients received the regimen
      of vinorelbine plus cisplatin (NP), the others received mitomycin, vindesine plus
      cisplatin (MVP). RESULTS: The overall response rates were 13.3% in NP and 0 in
      MVP (P > 0.05). Time to progression was longer for NP patients than that for MVP
      ones (6 v 3 months, P < 0.05), so was median survival (9 v 6 months, P < 0.05).
      The 1-year survival rate of 40.0% in the NP group was significantly higher than
      that of 0 in MVP (P < 0.05). Grade III-IV toxicity was observed at a similar rate
      in both groups (P > 0.05), though both well tolerated. CONCLUSION: Regimen of
      vinorelbine plus cisplatin is appropriate for good performance status patients
      with advanced non-small cell lung cancer previously treated with taxane-based
      chemotherapy. Time to progression, median survival and 1-year survival are
      satisfactory in patients treated with NP, which is complicated with acceptable
      toxicity.

PMID- 14690568
TI  - [Phase II clinical trial on gemcitabine in the treatment of stage IIIB-IV non
      small cell lung cancer].
AB  - OBJECTIVE: To evaluate the efficacy and safety of domestic Gemcitabine in the
      treatment of patients with stage IIIB approximately IV non-small cell lung cancer
      (NSCLC). METHODS: 124 NSCLC patients were randomized into three groups: Group A:
      single drug group, 40 cases, gemcitabine 1 000 mg/m(2) + NS 100 ml or 200 ml was
      infused within 30 approximately 60 minutes on D1, 8 and 15, with 28 days taken as
      one cycle. Group B: combined treatment group, 36 cases, in addition to the above
      protocol, cisplatin 30 mg/m(2) was infused within 60 approximately 120 min, on
      D1, 2 and 3. Group C: combined control group: 39 cases, the protocol applied was
      the same as group B except domestic gemcitabine being replaced by imported
      gemzar. The efficacy and side effects of treatment were evaluated after 8 weeks
      of treatment. RESULTS: 115 patients could be evaluated for response rate. PR was
      observed in 9/40 (22.5%) of group A, 15/36 (41.6%) in group B and 15/39 (38.36%)
      in group C. There was no significant difference of PR rates between group B and
      group C (P = 0.552). 117 patients who received the second cycle of treatment were
      evaluated for toxicity. The incidence of grade III approximately IV nausea,
      vomiting and loss of appetite was much higher in group B. Hematological toxicity
      of groups B and C was higher than that of group A. There was no significant
      difference between groups B and C. CONCLUSION: The efficacy and incidence of side
      effects between domestic gemcitabine and the imported gemzar are similar.

PMID- 14690570
TI  - [Combined gemcitabine and cisplatin in the treatment of advanced non-small cell
      lung cancer].
AB  - OBJECTIVE: To investigate the clinical efficacy and side effects of advanced non
      small cell lung cancer (NSCLC) treated by combined gemcitabine and cisplatin.
      METHODS: Forty-six patients with locally advanced (Stage IIIB) or metastatic
      (Stage IV) NSCLC were alloted to the study. The patients received gemcitabine 1
      000 mg/m(2) on D 1, 8, and cisplatin 80 mg on D 1 approximately 3 in the 21-day
      cycle. RESULTS: An objective response was obtained in 46% (21/46) of patients (1
      CR and 21 PR), whereas 19 patients had stable disease and 6 patients showed
      progressive disease. The response rate was 58.3% in untreated patients and 31.8%
      was obtained in treated ones. Significant difference was observed between the two
      groups (P < 0.05). The main toxicities were leukopenia and thrombocytopenia.
      CONCLUSION: The combination of gemcitabine and cisplatin, being feasible and well
      tolerated, should be taken as an energetic scheme in the treatment of advanced
      NSCLC.

PMID- 14690571
TI  - [Autologous peripheral blood stem cell transplantation in the treatment of
      patients with primary large mediastinal B-cell lymphoma].
AB  - OBJECTIVE: To evaluate the therapeutic effectiveness and safety of high dose
      chemoradiotherapy (HDC) combined with autologous peripheral blood stem cell
      transplantation (APBSCT) in the treatment of patients with primary large
      mediastinal B-cell lymphoma (PMLBL). METHODS: Among nine patients with PMLBL
      treated with APBSCT, high dose chemotherapy combined with total body irradiation
      (TBI) or total lymph node irradiation (TLI)/subtotal lymph node irradiation
      (STLI) were given to 7 patients and high dose chemotherapy only as pre
      transplantation regimen in 2 patients. All patients received supplementary
      irradiation at the primary mediastinum after transplantation. RESULTS: After a
      median follow-up of 24 (10 - 84) months, 5 patients achieved complete remission
      (CR) and 3 patients partial remission (PR) after induction chemotherapy. One
      patient developed progressive disease before transplantation. All 5 patients who
      achieved CR after induction chemotherapy became disease-free survivors (DFS). One
      of 3 patients who achieved PR after induction chemotherapy was DFS, the other two
      died in the third and fifth month, respectively. The patient who relapsed before
      transplantation died in the sixth month carrying the disease all along. According
      to the life table method, the cumulative probability of 7-year DFS and overall
      survival (OS) were both 66.7%. No transplant-related mortality was found.
      CONCLUSION: High dose chemoradiotherapy combined with autologous peripheral blood
      stem cell transplantation is a highly potential therapeutic treatment for poor
      prognostic primary mediastinal large B-cell lymphoma.

PMID- 14690572
TI  - [Surgical treatment of tonsillar cancer].
AB  - OBJECTIVE: To study the surgical treatment of tonsillar cancer. METHODS: Twenty
      four patients with tonsillar cancer were treated with surgery and postoperative
      radiotherapy. The choice of surgical procedure was decided on the condition of
      the lesion. The tumor was resected through the transoral approach, mandibular
      swing approach, mandibular resection approach or hyoid approach. Surgical defect
      was repaired by pectoralis major myocutaneous flap, sternohyoid myofascial flap,
      tongue flap or soft palate flap. RESULTS: The 3- and 5-year survival rates were
      76.0% and 60.8%. Function of chewing, deglutition, respiration and speech was
      restored well. CONCLUSION: Method of total resection of the tonsillar carcinoma
      through the optimum approach is best chosen according to the condition of the
      lesion, while preserving the oropharyngeal function. When combined with
      postoperative radiotherapy, the survival rate and quality of life of patients can
      be improved.

PMID- 14690573
TI  - [Topotecan-based combined chemotherapy for refractory or relapsed hematologic
      malignancies].
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of topotecan-based combined
      chemotherapy for refractory or relapsed hematologic malignancies. METHODS: Twenty
      one patients with refractory or relapsed acute leukemia (AL), non-Hodgkin's
      lymphoma (NHL) or high risk myelodysplastic syndrome (MDS) were treated by
      topotecan with cytarabine, amsacrine or cyclophosphamide. All patients received a
      single course as salvage therapy. RESULTS: The overall response rate of one
      course was 61.9% with 9/21 (42.9%) CR and 4/21 (19%) PR. Severe myelosuppression
      was observed in all patients. Agranulocytic time was 12.6 days in AL and 7.5 days
      in NHL. Sixteen of 21 patients received G-CSF 300 micro g/d All patients received
      supportive treatment of transfusion. Fever and documented infection developed in
      15 patients. Non-hematologic toxicity was mild. CONCLUSION: Topotecan-based
      combined chemotherapy has significant antitumour activity and acceptable toxicity
      as salvage therapy for high risk hematologic malignancies.

PMID- 14690574
TI  - [Combined preoperative xeloda and radiotherapy for lower rectal cancer].
AB  - OBJECTIVE: To evaluate the effect of combined preoperative xeloda and pelvic
      radiotherapy on locally advanced lower rectal cancer. METHODS: Sixty lower rectal
      cancer patients were divided randomly into two groups. 30 patients (Group A) were
      treated with operation alone and 30 patients (Group B) were treated with xeloda
      and radiotherapy before operation. RESULTS: The operative resection, anal
      preservation and local recurrence rates were 86.66%, 33.33%, 15.38% in group A
      and 100%, 83.33%, 0% in group B (P < 0.05 and P < 0.01). CONCLUSION: Combined
      preoperative xeloda and radiotherapy for lower rectal cancer is able to
      significantly improve the operative resection, anal preservation and decrease the
      local recurrence rates.

PMID- 14690575
TI  - [Intra-operative radionuclide lymphatic mapping in sentinel lymph node biopsy of
      breast cancer].
AB  - OBJECTIVE: To study intra-operative radionuclide lymphatic mapping in sentinel
      lymph node (SLN) biopsy of breast cancer. METHODS: Forty-two breast cancer
      (diameter </= 5.0 cm) patients with clinically negative axillary node were
      analyzed. 18.5 MBq/0.5 ml technetium-99m labeled sulfur colloid (labeling yield >
      98%, size of colloid granule 100 approximately 200 nm) was injected into the
      mammary tissue around the tumor or biopsy site at four points. SLN in breast
      cancer was detected and dissected with the help of lymphoscintigraphy and intra
      operative gamma probe. Routine lymph node dissection was performed for all
      patients. RESULTS: The detection rate was 88.1% in lymphoscintigraphy and 97.6%
      in intra-operative gamma probe detection for SLN in breast cancer. The
      sensitivity, accuracy, false negative and specificity of SLN biopsy were 93.3%
      (14 in 15), 97.6% (40 in 41), 6.7% (1 in 15) and 100% (26 in 26). CONCLUSION:
      Sentinel lymph node in breast cancer, detected by preoperative lymphoscintigraphy
      combined with intra-operative gamma probe, is able to predict regional lymph node
      metastasis. The successful rate of SLN biopsy can be raised by improvement in the
      quality of nuclear imaging agent, technic of injection and method of measurement.

PMID- 14690576
TI  - [Campto (CPT-11) treatment of advanced large intestinal cancer: clinical
      experience].
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of campto (CPT-11) monotherapy
      or combined with 5Fu + leucovorin (CF) in advanced large intestinal cancer.
      METHODS: 186 such patients were divided into campto monotherapy group and CPT-11
      plus 5Fu + CF [De Gramont (DGM) or Mayo protocal] groups. The mean dose of CPT-11
      was 270 mg/m(2) alone in the monotherapy group and 150 mg/m(2) in the combination
      group. Campto was given as iv infusion in no less than 30-minutes. RESULTS: 186
      patients were eligible for response evaluation. The response rates were 27.9% in
      the monotherapy group, 32.7% in CPT-11 + DGM and 27.3% in CPT-11 + Mayo group.
      For 55 untreated patients, the response rates of monotherapy, Campto + DGM and
      Campto + Mayo regime groups were 33.3%, 28.9% and 50.0%. For 131 treated
      patients, they were 26.4%, 34.8% and 22.2%, respectively. The toxicities of the
      whole group were 16.0% cholinergic syndrome, 51.9% delayed diarrhea and 19.8%
      leucopenia. There were 2 treatment-related deaths. CONCLUSION: The efficacy and
      toxicities of campto are similar as compared with the reports by other
      investigators.

PMID- 14690577
TI  - [Study of the pathology, immunophenotype, etiology and genetic marker of NK/T
      cell lymphoma].
AB  - OBJECTIVE: To study the NK/T-cell lymphoma, search for a more efficacious and
      simpler method and establish a standard guideline for distinguishing the NK-like
      T-cell lymphoma from the NK-cell lymphoma. METHODS: Thirty-four NK or T-cell
      lymphomas from the upper aerodigestive tract (n = 22), skin (n = 2),
      gastrointestinal (GI) tract (n = 2), lymph nodes (n = 7), and other sites (n = 1)
      were studied. Immunophenotype was analyzed by immunohistochemistry. In situ
      hybridization with EBER 1/2 RNA probes was performed. T-cell receptor (TCR)-beta
      and -gamma gene rearrangement was analyzed by polymerase chain reaction (PCR).
      RESULTS: Eighteen cases were positive for CD(56) and 16 for TIA-1 in 34 lymphomas
      cases. All tumor cells in the skin cases were positive for Ki-67. Epstein-Barr
      virus (EBV) mRNA was detected in 12 upper aerodigestive tumors including 9 of 12
      nasal and 3 extranasal tumors. EBER was also detected in 1 of 2 skin lymphomas
      and both of the 2 GI lymphomas. Clonal TCR-beta and -gamma gene rearrangement was
      detected in 2 of 22 upper aerodigestive, all of the skin and GI lymphomas, and 6
      of 9 nodal and other site lymphomas. CONCLUSION: Most upper aerodigestive NK/T
      cell lymphomas are genotypically NK derivation, and a few belong to T lineage.
      However, NK-like T-cell lymphomas more frequently seen in skin and GI tract.
      Nodal NK-cell lymphoma are quite rare. These two kinds of lymphomas can only be
      diagnosed with additional immunohistochemical markers, EBER detection by ISH, TCR
      gene rearrangement or NK-cell receptors (NKRs) RNA detection. Detection of TCR
      rearrangement remains the important standard for the diagnosis of T-cell
      lymphoma.

PMID- 14690578
TI  - [Explore the origin of H/RS cells on protein and gene].
AB  - OBJECTIVE: To explore the origin and clonality of H/RS cells. METHODS:
      Immunohistochemical method was used to detect the expression of B-cell-specific
      activator protein (BSAP) and CD(20) in 33 paraffin-embedded tissues of classical
      Hodgkin lymphoma (cHL). IgH gene rearrangement was detected in 33 paraffin
      embedded cHL tissue and 6 microsectioned H/RS cell samples. The PCR products of a
      case of cHL and its microsectioned cells were sequenced. RESULTS: H/RS cells were
      positive for BSAP in 30 of 33 (90.91%) cHL cases and positive for CD(20) in 10/33
      (30.30%) cases. There was a significant difference between the expression of BSAP
      and CD(20) in H/RS cells (P = 0.000). BSAP and CD(20) were positive in almost all
      B cells of lymph node reactive hyperplasia and malignant cells in B-cell
      lymphomas while were negative in all malignant cells of T-cell lymphomas. 16 of
      33 cHL were positive for gene rearrangement, and microsectioned H/RS cells in 14
      of 19 tubes displayed clonal bands of rearrangement. There was no significant
      difference among the rearrangement rates in tubes containing different numbers of
      H/RS cells (P = 0.280). Sequencing analyses of the PCR products from both
      paraffin-embedded tissue and microsection of the same patient revealed the
      rearranged V segments, but the sequences were not identical. CONCLUSION: H/RS
      cells were originated from B cells of different differentiation stage.

PMID- 14690579
TI  - [Detection of IgH-MMSET fusion gene in multiple myeloma patients and its
      significance].
AB  - OBJECTIVE: To detect the IgH-MMSET fusion gene resulted from t (4;14)
      translocation in multiple myeloma and illuminate its significance. METHODS: IgH
      MMSET fusion gene was detected in bone marrow specimens of 25 multiple myeloma
      (MM) patients and MM cell line NCI-H929 using reverse-transcription PCR (RT-PCR)
      assay followed by nested PCR to increase the sensitivity. The purified PCR
      products were cloned into pGEM-T vector and then sequenced using M13 forward
      primers. The fragment sequences were compared with that in GenBank to find
      matched sequences. RESULTS: Only a 438 base pair long fragment was obtained after
      RT-PCR assay and was confirmed by sequencing to be a fusion gene product of IgH
      gene and MMSET gene in MM cell line NCI-H929. The breakpoints were located within
      the C micro region of IgH gene on chromosome 14 and intron 3 of MMSET gene on
      chromosome 4. IgH-MMSET hybrid transcripts were detected in 3 of 25 MM patients
      through nested PCR assay. The amplified fragments of the 3 patients were 237 base
      pairs (bp), 239 bp and 239 bp in length, respectively. The breakpoints on
      chromosome 4 were identical to that of NCI-H929 cell. CONCLUSIONS: The formation
      of IgH-MMSET fusion gene is resulted from t (4;14) translocation in MM. The
      incidence rate is 12.0%. The presence of IgH-MMSET fusion gene may predict poor
      prognosis.

PMID- 14690580
TI  - [The WHO (1997) classification of 370 cases of malignant lymphomas].
AB  - OBJECTIVE: To reclassify retrospectively 370 cases of malignant lymphomas.
      METHODS: According to the WHO new classification, the clinical features and
      pathology as well as immunophenotype of 370 lymphomas were analysed. RESULTS: In
      the 370 lymphomas, there were 359 non-Hodgkin's lymphomas (NHL) (97.03%) and 11
      Hodgkin's lymphomas (HL) (2.97%). Of the 359 NHL, 246 were B-cell lymphomas
      (68.52%), 108 T-cell lymphomas (30.08%), 1 each histiocytic lymphoma and
      follicular dendritic cell sarcoma, and 3 NK cell lymphomas. The extranodal
      lymphomas were 196 cases (54.6%) and the nodal lymphomas 163 cases (45.4%). The
      incidence of NHL categories were in proper order as follows: diffuse large B cell
      lymphoma (173 cases, 48.2%) > peripheral T cell lymphoma (54 cases, 15.0%) >
      mucosa associated lymphoid tissue (MALT) lymphoma (31 cases, 8.6%) > NK/T cell
      lymphoma (25 cases, 7.0%) > follicular lymphoma (21 cases, 5.8%) > anaplastic
      large cell lymphoma (12 cases, 3.3%). CONCLUSION: The results suggested that the
      study of malignant lymphomas with WHO new classification have important clinical
      significance.

PMID- 14690581
TI  - [The clinical significance of cyclin B1 expression in adult acute leukemia
      patients].
AB  - OBJECTIVE: To investigate the clinical significance of cyclin B1 expression in
      adult acute leukemia (AL) patients. METHODS: The expression of cyclin B1 and p21
      and their cell cycle distribution were measured by flow cytometry in 85 adult
      patients with de novo AL, 10 continuous complete remission (CCR) AL and 17 normal
      controls (NC). The mRNAs of cyclin B1, p21 cip1 and proliferation cell nuclear
      antigen (PCNA) in patients and NCs were measured with semi-quantity reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: Cyclin B1 protein
      expression in de novo AL patients was significantly higher than that in NC (P <
      0.001). It was higher in relapsed patients than in NC (P < 0.05) but was lower
      than in de novo AL (P < 0.01). There was no difference between the remission
      cases and NC (P = 0.21), and between CCR patients and NC (P > 0.05). The cyclin
      B1 overexpression ratio was higher than that of NC. A negative correlation
      between the expression levels of cyclin B1 and P21 was observed (r = -0.266, P <
      0.05). The cyclin B1 protein expression level was positively correlated with its
      mRNA level. The expression of cyclin B1 was positively correlated with
      proliferation index (PI) levels, and with PCNA levels (rPI = 0.7314, rPCNA =
      0.7152). Remission rate was higher in high cyclin B1 expression patients than in
      normal cyclin B1 expression patients (P < 0.01), so did the relapse rate (P <
      0.01). Patients with higher cyclin B1 expression had higher survival rate.
      CONCLUSION: Cyclin B1 was overexpressed and abnormally distributed in cell cycle
      phases in de novo AL patients. Overexpression of cyclin B1 might be a favorable
      prognostic factor for patients with AL.

PMID- 14690582
TI  - [Study on DNA methylation status of WT1 gene promoter in leukemia cell].
AB  - OBJECTIVE: To analyse the WT1 expression and its DNA methylation status of its
      promoter domain. METHOD: The expression of WT1 gene and its DNA methylation
      status were assayed in leukemia cell lines and normal peripheral blood
      mononuclear cells (PBMNC) by RT-PCR and MS-PCR. RESULTS: WT1 was overexpressed in
      HL60, K562 and KG1 leukemia cell lines, but not in U937 and PBMNC. Methylation of
      WT1 promoter was not observed in HL60 cells. CONCLUSION: DNA methylation of WT1
      gene promotor did not inhibit its expression. Other mechanisms may appear to
      regulate the WT1 expression.

PMID- 14690583
TI  - [The clinical features of severe aplastic anemia patients with complication of
      infection].
AB  - OBJECTIVE: To study the clinical features of severe aplastic anemia (SAA)
      patients with complication of infection. METHODS: A retrospective analysis of
      prevalence of infection occurring in 229 SAA patients, their bacterial spectrum,
      and the effect of GM-CSF or G-CSF on the infection were done. RESULT: The
      prevalence of infection in SAA patients was 86.0%, among which 54.2% was infected
      with gram-positive organisms, 40.0% with gram-negative bacilli and 5.8% with
      fungal infections. Septicemia occurred mostly with E. coli and Pseudomonas
      infection. Patient's neutropenia was significantly related to the infection. The
      patients with neutrophil count less than 0.2 x 10(9)/L had more frequent and
      severe infection. Age, hemoglobin level, subtype of T lymphocytes and
      antithymocyte globulin therapy were not related to infection. Prophylaxis usage
      of floxacin could not reduce patient' gastrointestinal infection. The total
      mortality of SAA patients with infection was 23.1%. Pulmonary infection and
      septicemia increased mortality, and GM-CSF/G-CSF therapy reduce mortality.
      CONCLUSION: SAA patients were at high risk of infection which was significantly
      associated with severe neutropenia. GM-CSF or G-CSF therapy exerts an assistant
      role to antibiotics in controlling the infections.

PMID- 14690584
TI  - [An analysis of relapse and risk factors of autoimmune hemolytic anemia and Evans
      syndrome].
AB  - OBJECTIVE: To analyse the relapse rate and risk factors of autoimmune hemolytic
      anemia (AIHA) and Evans syndrome. METHODS: Fifty two cases of AIHA and Evans
      syndrome in remission being followed up for 1 - 14 years (median time 3.8 years)
      were analysed for relapse rate. The risk factors of relapse were analysed by case
      control study. RESULTS: The total relapse rate of these AIHA and Evans syndrome
      patients was 57.7%, and the median remission duration to the first relapse was 9
      months. The relapse rates in patients with negative Coombs test, warm
      autoantibodies and both of warm and cold autoantibodies were 30.8% (4/13), 54.0%
      (13/24) and 86.7% (13/15), respectively. The relapse rate in patients with cold
      antibody was the highest (P < 0.05). The relapse rate in patients with antibody
      titer >or= 100 was 92.9% (13/14) and was higher than that in patients with
      antibody titer < 100 [59.5% (13/22)] (P < 0.05). Patients treated with prednisone
      and cyclosporin relapsed less than those treated with prednisone alone, and the
      relapse was related to the therapy course of prednisone and CsA. CONCLUSION:
      Because of the high relapse rate, AIHA and Evans syndrome should be treated
      according to the class of autoantibodies, and with longer course of prednisone
      and cyclosporin and prophylaxis of infection.

PMID- 14690586
TI  - Functional Genomics: all the king's horses and all the king's men can put Humpty
      together again.
AB  - The integration of data from different kinds of high-throughput functional
      genomic analyses not only permits the accurate determination of the functions of
      novel genes, but also presents the prospect of a "systems" approach to biology in
      the future.

PMID- 14690587
TI  - Pinning NF-kappaB to the nucleus.
AB  - The peptidyl-prolyl isomerase Pin1 binds and stabilizes several phosphorylated
      transcription and mitosis regulators via its WW interacting domain. It is
      overexpressed in breast tumors and, as discuss in this issue of Molecular Cell,
      could account for their constitutive nuclear NF-kappaB expression. The proposed
      mechanism involves protection of Pin1-bound p65 against SOCS-1-mediated
      ubiquitination.

PMID- 14690588
TI  - Myosins motor Miranda.
AB  - New evidence shows that myosin motors drive the spatial segregation of cell fate
      determinants during asymmetric cell division. How they do so remains a mystery.

PMID- 14690589
TI  - Posttranscriptional generation of macromolecular complexes.
AB  - Discrete classes of mRNAs that encode functionally related proteins are
      associated with sequence-specific RNA-binding proteins in yeast and mammalian
      cells. recently reported that pre-mRNAs encoding components of inhibitory
      synapses are bound to neuron-specific Nova RNA-binding proteins.

PMID- 14690590
TI  - The missing linker: an unexpected role for a histone deacetylase.
AB  - Molecular motors are the long-haul carriers of eukaryotic cells, moving cargos
      bidirectionally along microtubule tracks. In the December 12th issue of Cell,
      report that HDAC6, a tubulin deacetylase, functions as an adaptor that links
      cargos of aggregated protein to the minus end-directed motor, cytoplasmic dynein.

PMID- 14690591
TI  - Assigning function to yeast proteins by integration of technologies.
AB  - Interpreting genome sequences requires the functional analysis of thousands of
      predicted proteins, many of which are uncharacterized and without obvious
      homologs. To assess whether the roles of large sets of uncharacterized genes can
      be assigned by targeted application of a suite of technologies, we used four
      complementary protein-based methods to analyze a set of 100 uncharacterized but
      essential open reading frames (ORFs) of the yeast Saccharomyces cerevisiae. These
      proteins were subjected to affinity purification and mass spectrometry analysis
      to identify copurifying proteins, two-hybrid analysis to identify interacting
      proteins, fluorescence microscopy to localize the proteins, and structure
      prediction methodology to predict structural domains or identify remote
      homologies. Integration of the data assigned function to 48 ORFs using at least
      two of the Gene Ontology (GO) categories of biological process, molecular
      function, and cellular component; 77 ORFs were annotated by at least one method.
      This combination of technologies, coupled with annotation using GO, is a powerful
      approach to classifying genes.

PMID- 14690592
TI  - Evidence that structural rearrangements and/or flexibility during TCR binding can
      contribute to T cell activation.
AB  - While in many cases the half-life of T cell receptor (TCR) binding to a
      particular ligand is a good predictor of activation potential, numerous
      exceptions suggest that other physical parameter(s) must also play a role.
      Accordingly, we analyzed the thermodynamics of TCR binding to a series of peptide
      MHC ligands, three of which are more stimulatory than their stability of binding
      would predict. Strikingly, we find that during TCR binding these outliers show
      anomalously large changes in heat capacity, an indicator of conformational change
      or flexibility in a binding interaction. By combining the values for heat
      capacity (DeltaCp) and the half-life of TCR binding (t(1/2)), we find that we can
      accurately predict the degree of T cell stimulation. Structural analysis shows
      significant changes in the central TCR contact residue of the peptide-MHC,
      indicating that structural rearrangements within the TCR-peptide-MHC interface
      can contribute to T cell activation.

PMID- 14690593
TI  - Structural basis for recruitment of the adaptor protein APS to the activated
      insulin receptor.
AB  - The adaptor protein APS is a substrate of the insulin receptor and couples
      receptor activation with phosphorylation of Cbl to facilitate glucose uptake. The
      interaction with the activated insulin receptor is mediated by the Src homology 2
      (SH2) domain of APS. Here, we present the crystal structure of the APS SH2 domain
      in complex with the phosphorylated tyrosine kinase domain of the insulin
      receptor. The structure reveals a novel dimeric configuration of the APS SH2
      domain, wherein the C-terminal half of each protomer is structurally divergent
      from conventional, monomeric SH2 domains. The APS SH2 dimer engages two kinase
      molecules, with pTyr-1158 of the kinase activation loop bound in the canonical
      phosphotyrosine binding pocket of the SH2 domain and a second phosphotyrosine,
      pTyr-1162, coordinated by two lysine residues in beta strand D. This structure
      provides a molecular visualization of one of the initial downstream recruitment
      events following insulin activation of its dimeric receptor.

PMID- 14690594
TI  - Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into
      myotubular myopathy and Charcot-Marie-Tooth syndrome.
AB  - Myotubularin-related proteins are a large subfamily of protein tyrosine
      phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids.
      Mutations in members of the myotubularin family cause the human neuromuscular
      disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. The
      crystal structure of a representative member of this family, MTMR2, reveals a
      phosphatase domain that is structurally unique among PTPs. A series of mutants
      are described that exhibit altered enzymatic activity and provide insight into
      the specificity of myotubularin phosphatases toward phosphoinositide substrates.
      The structure also reveals that the GRAM domain, found in myotubularin family
      phosphatases and predicted to occur in approximately 180 proteins, is part of a
      larger motif with a pleckstrin homology (PH) domain fold. Finally, the MTMR2
      structure will serve as a model for other members of the myotubularin family and
      provide a framework for understanding the mechanism whereby mutations in these
      proteins lead to disease.

PMID- 14690595
TI  - Crystal structure of ARF1*Sec7 complexed with Brefeldin A and its implications
      for the guanine nucleotide exchange mechanism.
AB  - ARF GTPases are activated by guanine nucleotide exchange factors (GEFs) of the
      Sec7 family that promote the exchange of GDP for GTP. Brefeldin A (BFA) is a
      fungal metabolite that binds to the ARF1*GDP*Sec7 complex and blocks GEF activity
      at an early stage of the reaction, prior to guanine nucleotide release. The
      crystal structure of the ARF1*GDP*Sec7*BFA complex shows that BFA binds at the
      protein-protein interface to inhibit conformational changes in ARF1 required for
      Sec7 to dislodge the GDP molecule. Based on a comparative analysis of the
      inhibited complex, nucleotide-free ARF1*Sec7 and ARF1*GDP, we suggest that, in
      addition to forcing nucleotide release, the ARF1-Sec7 binding energy is used to
      open a cavity on ARF1 to facilitate the rearrangement of hydrophobic core
      residues between the GDP and GTP conformations. Thus, the Sec7 domain may act as
      a dual catalyst, facilitating both nucleotide release and conformational
      switching on ARF proteins.

PMID- 14690596
TI  - Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and
      ubiquitin-mediated proteolysis of p65/RelA.
AB  - The transcription factor NF-kappaB is activated by the degradation of its
      inhibitor IkappaBalpha, resulting in its nuclear translocation. However, the
      mechanism by which nuclear NF-kappaB is subsequently regulated is not clear. Here
      we demonstrate that NF-kappaB function is regulated by Pin1-mediated prolyl
      isomerization and ubiquitin-mediated proteolysis of its p65/RelA subunit. Upon
      cytokine treatment, Pin1 binds to the pThr254-Pro motif in p65 and inhibits p65
      binding to IkappaBalpha, resulting in increased nuclear accumulation and protein
      stability of p65 and enhanced NF-kappaB activity. Significantly, Pin1-deficient
      mice and cells are refractory to NF-kappaB activation by cytokine signals.
      Moreover, the stability of p65 is controlled by ubiquitin-mediated proteolysis,
      facilitated by a cytokine signal inhibitor, SOCS-1, acting as a ubiquitin ligase.
      These findings uncover two important mechanisms of regulating NF-kappaB signaling
      and offer new insight into the pathogenesis and treatment of some human diseases
      such as cancers.

PMID- 14690597
TI  - The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for
      selective ubiquitin-like protein activation by an E1.
AB  - E1 enzymes initiate ubiquitin-like protein (ubl) transfer cascades by catalyzing
      adenylation of the ubl's C terminus. An E1's selectivity for its cognate ubl is
      essential because the E1 subsequently coordinates the ubl with its correct
      downstream pathway. We report here the structure of the 120 kDa quaternary
      complex between human APPBP1-UBA3, a heterodimeric E1, its ubl NEDD8, and ATP.
      The E1 selectively recruits NEDD8 through a bipartite interface, involving a
      domain common to all ubl activating enzymes including bacterial ancestors, and
      also eukaryotic E1-specific sequences. By modeling ubiquitin into the NEDD8
      binding site and performing mutational analysis, we identify a single conserved
      arginine in APPBP1-UBA3 that acts as a selectivity gate, preventing misactivation
      of ubiquitin by NEDD8's E1. NEDD8 residues that interact with E1 correspond to
      residues in ubiquitin important for binding the proteasome and other ubiquitin
      interacting proteins, suggesting that the conjugation and recognition machineries
      have coevolved for each specific ubl.

PMID- 14690598
TI  - Genome-wide analysis of mRNAs regulated by the nonsense-mediated and 5' to 3'
      mRNA decay pathways in yeast.
AB  - Transcripts regulated by the yeast nonsense-mediated and 5' to 3' mRNA decay
      pathways were identified by expression profiling of wild-type, upf1Delta,
      nmd2Delta, upf3Delta, dcp1Delta, and xrn1Delta cells. This analysis revealed that
      inactivation of Upf1p, Nmd2p, or Upf3p has identical effects on global RNA
      accumulation; inactivation of Dcp1p or Xrn1p exhibits both common and unique
      effects on global RNA accumulation but causes upregulation of only a small
      fraction of transcripts; and the majority of transcripts upregulated in upf/nmd
      strains are also upregulated to similar extents in dcp1Delta and xrn1Delta
      strains. Our results define the core transcripts regulated by NMD, identify
      several novel structural classes of NMD substrates, demonstrate that nonsense
      containing mRNAs are primarily degraded by the 5' to 3' decay pathway even in the
      absence of functional NMD, and indicate that 3' to 5' decay, not 5' to 3' decay,
      may be the major mRNA decay activity in yeast cells.

PMID- 14690599
TI  - Cytoplasmic degradation of splice-defective pre-mRNAs and intermediates.
AB  - Specific systems of nuclear RNA degradation appear to target and degrade aberrant
      pre-mRNA molecules. In this work we report on a Dbr1p-dependent RNA decay pathway
      that limits the accumulation of splice-defective lariat intermediates stalled at
      the second step of splicing. In this pathway, splice-defective lariat
      intermediates are debranched by Dbr1p and subsequently degraded 5' to 3'
      primarily by the cytoplasmic exonuclease, Xrn1p. When debranching is blocked,
      these splicing intermediates can be degraded in a 3' to 5' direction in a manner
      dependent on Ski2p, a cofactor for the cytoplasmic exosome. In that Xrn1p and
      Ski2p are cytoplasmic and Dbr1p localizes to both the nucleus and the cytoplasm,
      these data suggest that this decay pathway occurs within the cytoplasm.
      Furthermore, the finding that lariat intermediates accumulate in the dbr1Delta
      strain suggests that this pathway also functions as an inherent quality control
      mechanism for the process of pre-mRNA splicing.

PMID- 14690600
TI  - A mechanism for the regulation of pre-mRNA 3' processing by human cleavage factor
      Im.
AB  - Human cleavage factor I(m) (CFI(m)) is a heterodimeric RNA binding protein
      complex that functions at an early step in the assembly of the pre-mRNA 3'
      processing complex. In this report we show that CFI(m) can stimulate both
      cleavage and poly(A) addition, and can act to suppress poly(A) site cleavage in a
      sequence-dependent manner. Elevated levels of CFI(m) suppressed cleavage at the
      primary poly(A) site of the pre-mRNA encoding the 68 kDa subunit of CFI(m).
      CFI(m)-mediated suppression of poly(A) site cleavage was dependent upon the
      presence of three copies of an RNA element initially identified by CFI(m)-SELEX.
      These data provide evidence for a mechanism for the regulation of poly(A) site
      selection by a basal pre-mRNA 3' processing factor.

PMID- 14690601
TI  - Bacterial mitosis: ParM of plasmid R1 moves plasmid DNA by an actin-like
      insertional polymerization mechanism.
AB  - Bacterial DNA segregation takes place in an active and ordered fashion. In the
      case of Escherichia coli plasmid R1, the partitioning system (par) separates
      paired plasmid copies and moves them to opposite cell poles. Here we address the
      mechanism by which the three components of the R1 par system act together to
      generate the force required for plasmid movement during segregation. ParR protein
      binds cooperatively to the centromeric parC DNA region, thereby forming a complex
      that interacts with the filament-forming actin-like ParM protein in an ATP
      dependent manner, suggesting that plasmid movement is powered by insertional
      polymerization of ParM. Consistently, we find that segregating plasmids are
      positioned at the ends of extending ParM filaments. Thus, the process of R1
      plasmid segregation in E. coli appears to be mechanistically analogous to the
      actin-based motility operating in eukaryotic cells. In addition, we find evidence
      suggesting that plasmid pairing is required for ParM polymerization.

PMID- 14690602
TI  - ERCC1/XPF removes the 3' overhang from uncapped telomeres and represses formation
      of telomeric DNA-containing double minute chromosomes.
AB  - Human telomeres are protected by TRF2. Inhibition of this telomeric protein
      results in partial loss of the telomeric 3' overhang and chromosome end fusions
      formed through nonhomologous end-joining (NHEJ). Here we report that ERCC1/XPF
      deficient cells retained the telomeric overhang after TRF2 inhibition,
      identifying this nucleotide excision repair endonuclease as the culprit in
      overhang removal. Furthermore, these cells did not accumulate telomere fusions,
      suggesting that overhang processing is a prerequisite for NHEJ of telomeres.
      ERCC1/XPF was also identified as a component of the telomeric TRF2 complex.
      ERCC1/XPF-deficient mouse cells had a novel telomere phenotype, characterized by
      Telomeric DNA-containing Double Minute chromosomes (TDMs). We speculate that TDMs
      are formed through the recombination of telomeres with interstitial telomere
      related sequences and that ERCC1/XPF functions to repress this process.
      Collectively, these data reveal an unanticipated involvement of the ERCC1/XPF NER
      endonuclease in the regulation of telomere integrity and establish that TRF2
      prevents NHEJ at telomeres through protection of the telomeric overhang from
      ERCC1/XPF.

PMID- 14690603
TI  - Branch migrating sister chromatid junctions form at replication origins through
      Rad51/Rad52-independent mechanisms.
AB  - Cells overcome intra-S DNA damage and replication impediments by coupling
      chromosome replication to sister chromatid-mediated recombination and replication
      bypass processes. Further, molecular junctions between replicated molecules have
      been suggested to assist sister chromatid cohesion until anaphase. Using two
      dimensional gel electrophoresis, we have identified, in yeast cells, replication
      dependent X-shaped molecules that appear during origin activation, branch
      migrate, and distribute along the replicon through a mechanism influenced by the
      rate of fork progression. Their formation is independent of Rad51- and Rad52
      mediated homologous recombination events and is not affected by DNA damage or
      replication blocks. Further, in hydroxyurea-treated rad53 mutants, altered in the
      replication checkpoint, the branched molecules progressively degenerate and
      likely contribute to generate pathological structures. We suggest that cells
      couple sister chromatid tethering with replication initiation by generating
      specialized joint molecules resembling hemicatenanes: this process might prime
      cohesion and assist sister chromatid-mediated recombination and replication
      events.

PMID- 14690604
TI  - Checkpoint failure and chromosomal instability without lymphomagenesis in
      Mre11(ATLD1/ATLD1) mice.
AB  - In this study, mice expressing one of the two Mre11 alleles inherited in the
      human ataxia-telangiectasia like disorder (A-TLD) were derived. The mutation had
      a profound maternal effect on embryonic viability, revealing an acute requirement
      for Mre11 complex function in early embryogenesis. Mre11(ATLD1/ATLD1) mice
      exhibited several indices of impaired ATM function. The mice also exhibited
      pronounced chromosomal instability. Despite this phenotypic spectrum, the animals
      were not prone to malignancy. These data indicate that defective cell cycle
      checkpoints and chromosomal instability are insufficient to significantly enhance
      the initiation of tumorigenesis. In contrast, the latency of malignancy in p53(+/
      ) mice was dramatically reduced. We propose that in Mre11(ATLD1/ATLD1) mice,
      genome instability and cell cycle checkpoint defects reduce viability in early
      embryos and in proliferating cells, while promoting malignancy in the context of
      an initiating lesion.

PMID- 14690605
TI  - The Saccharomyces cerevisiae helicase Rrm3p facilitates replication past
      nonhistone protein-DNA complexes.
AB  - The Saccharomyces cerevisiae RRM3 gene encodes a 5' to 3' DNA helicase. While
      replication of most of the yeast genome was not dependent upon Rrm3p, in its
      absence, replication forks paused and often broke at an estimated 1400 discrete
      sites, including tRNA genes, centromeres, inactive replication origins, and
      transcriptional silencers. These replication defects were associated with
      activation of the intra-S phase checkpoint. Activation of the checkpoint was
      critical for viability of rrm3Delta cells, especially at low temperatures. Each
      site whose replication was affected by Rrm3p is assembled into a nonnucleosomal
      protein-DNA complex. At tRNA genes and the silent mating type loci, disruption of
      these complexes eliminated dependence upon Rrm3p. These data indicate that the
      Rrm3p DNA helicase helps replication forks traverse protein-DNA complexes,
      naturally occurring impediments that are encountered in each S phase.

PMID- 14690606
TI  - CoCoA, a nuclear receptor coactivator which acts through an N-terminal activation
      domain of p160 coactivators.
AB  - The p160 coactivators bind to and potentiate transcriptional activation by
      nuclear receptors by recruiting secondary coactivators such as the histone
      acetyltransferases p300 and CBP and the protein methyltransferase CARM1. The
      function of the highly conserved N-terminal basic-helix-loop-helix/Per-Arnt-Sim
      (bHLH-PAS) domain of p160 coactivators is unknown. This region is required for
      coactivator synergy among p160, p300, and CARM1 coactivators. We identified a
      coactivator, coiled-coil coactivator (CoCoA), which binds to this domain and
      thereby enhances transcriptional activation by the estrogen receptor and other
      nuclear receptors. Endogenous CoCoA was found simultaneously with p160
      coactivators on the promoter of an endogenous estrogen-responsive gene. Reduction
      of endogenous cellular CoCoA levels inhibited the estrogen-stimulated expression
      of transiently transfected and endogenous genes. Moreover, CoCoA cooperated
      synergistically with GRIP1, CARM1, and p300 to enhance ER-mediated transcription.
      Thus, the N-terminal region of p160 coactivators contains an additional
      activation domain which contributes to coactivator function by recruitment of
      CoCoA.

PMID- 14690607
TI  - Mechanism of SMRT corepressor recruitment by the BCL6 BTB domain.
AB  - BCL6 encodes a transcription factor that represses genes necessary for the
      terminal differentiation of lymphocytes within germinal centers, and the
      misregulated expression of this factor is strongly implicated in several types of
      B cell lymphoma. The homodimeric BTB domain of BCL6 (also known as the POZ
      domain) is required for the repression activity of the protein and interacts
      directly with the SMRT and N-CoR corepressors that are found within large
      multiprotein histone deacetylase-containing complexes. We have identified a 17
      residue fragment from SMRT that binds to the BCL6 BTB domain, and determined the
      crystal structure of the complex to 2.2 A. Two SMRT fragments bind symmetrically
      to the BCL6 BTB homodimer and, in combination with biochemical and in vivo data,
      the structure provides insight into the basis of transcriptional repression by
      this critical B cell lymphoma protein.

PMID- 14690608
TI  - A Snf2 family ATPase complex required for recruitment of the histone H2A variant
      Htz1.
AB  - Deletions of three yeast genes, SET2, CDC73, and DST1, involved in
      transcriptional elongation and/or chromatin metabolism were used in conjunction
      with genetic array technology to screen approximately 4700 yeast deletions and
      identify double deletion mutants that produce synthetic growth defects. Of the
      five deletions interacting genetically with all three starting mutations, one
      encoded the histone H2A variant Htz1 and three encoded components of a novel 13
      protein complex, SWR-C, containing the Snf2 family ATPase, Swr1. The SWR-C also
      copurified with Htz1 and Bdf1, a TFIID-interacting protein that recognizes
      acetylated histone tails. Deletions of the genes encoding Htz1 and seven
      nonessential SWR-C components caused a similar spectrum of synthetic growth
      defects when combined with deletions of 384 genes involved in transcription,
      suggesting that Htz1 and SWR-C belong to the same pathway. We show that
      recruitment of Htz1 to chromatin requires the SWR-C. Moreover, like Htz1 and
      Bdf1, the SWR-C promotes gene expression near silent heterochromatin.

PMID- 14690609
TI  - Partitioning and plasticity of repressive histone methylation states in mammalian
      chromatin.
AB  - Methylation of position-specific lysine residues in histone N termini is a
      central modification for regulating epigenetic transitions in chromatin. Each
      methylatable lysine residue can exist in a mono-, di-, or trimethylated state,
      thereby extending the indexing potential of this particular modification. Here,
      we examine all possible methylation states for histone H3 lysine 9 (H3-K9) and
      lysine 27 (H3-K27) in mammalian chromatin. Using highly specific antibodies
      together with quantitative mass spectrometry, we demonstrate that pericentric
      heterochromatin is selectively enriched for H3-K27 monomethylation and H3-K9
      trimethylation. This heterochromatic methylation profile is dependent on the
      Suv39h histone methyltransferases (HMTases) but independent of the euchromatic
      G9a HMTase. In Suv39h double null cells, pericentric heterochromatin is converted
      to alternative methylation imprints and accumulates H3-K27 trimethylation and H3
      K9 monomethylation. Our data underscore the selective presence of distinct
      histone lysine methylation states in partitioning chromosomal subdomains but also
      reveal a surprising plasticity in propagating methylation patterns in eukaryotic
      chromatin.

PMID- 14690610
TI  - Histone methyltransferases direct different degrees of methylation to define
      distinct chromatin domains.
AB  - The functional significance of mono-, di-, and trimethylation of lysine residues
      within histone proteins remains unclear. Antibodies developed to selectively
      recognize each of these methylated states at histone H3 lysine 9 (H3 Lys9)
      demonstrated that mono- and dimethylation localized specifically to silent
      domains within euchromatin. In contrast, trimethylated H3 Lys9 was enriched at
      pericentric heterochromatin. Enzymes known to methylate H3 Lys9 displayed
      remarkably different enzymatic properties in vivo. G9a was responsible for all
      detectable H3 Lys9 dimethylation and a significant amount of monomethylation
      within silent euchromatin. In contrast, Suv39h1 and Suv39h2 directed H3 Lys9
      trimethylation specifically at pericentric heterochromatin. Thus, different
      methylated states of H3 Lys9 are directed by specific histone methyltransferases
      to "mark" distinct domains of silent chromatin.

PMID- 14690612
TI  - TOR and PKA signaling pathways converge on the protein kinase Rim15 to control
      entry into G0.
AB  - The highly conserved Tor kinases (TOR) and the protein kinase A (PKA) pathway
      regulate cell proliferation in response to growth factors and/or nutrients. In
      Saccharomyces cerevisiae, loss of either TOR or PKA causes cells to arrest growth
      early in G(1) and to enter G(0) by mechanisms that are poorly understood. Here we
      demonstrate that the protein kinase Rim15 is required for entry into G(0)
      following inactivation of TOR and/or PKA. Induction of Rim15-dependent G(0)
      traits requires two discrete processes, i.e., nuclear accumulation of Rim15,
      which is negatively regulated both by a Sit4-independent TOR effector branch and
      the protein kinase B (PKB/Akt) homolog Sch9, and release from PKA-mediated
      inhibition of its protein kinase activity. Thus, Rim15 integrates signals from at
      least three nutrient-sensory kinases (TOR, PKA, and Sch9) to properly control
      entry into G(0), a key developmental process in eukaryotic cells.

PMID- 14690611
TI  - Histone H2A/H2B dimer exchange by ATP-dependent chromatin remodeling activities.
AB  - ATP-dependent chromatin remodeling activities function to manipulate chromatin
      structure during gene regulation. One of the ways in which they do this is by
      altering the positions of nucleosomes along DNA. Here we provide support for the
      ability of these complexes to move nucleosomes into positions in which DNA is
      unraveled from one edge. This is expected to result in the loss of histone-DNA
      contacts that are important for retention of one H2A/H2B dimer within the
      nucleosome. Consistent with this we find that several chromatin remodeling
      complexes are capable of catalyzing the exchange of H2A/H2B dimers between
      chromatin fragments in an ATP-dependent reaction. This provides eukaryotes with
      additional means by which they may manipulate chromatin structure.

PMID- 14690613
TI  - Conditional protein alleles using knockin mice and a chemical inducer of
      dimerization.
AB  - We have developed a general method of making conditional alleles that allows the
      rapid and reversible regulation of specific proteins. A mouse line was produced
      in which proteins encoded by the endogenous glycogen synthase kinase-3 beta (GSK
      3beta) gene are fused to an 89 amino acid tag, FRB*. FRB* causes the
      destabilization of GSK-3beta, producing a severe loss-of-function allele. In the
      presence of C20-MaRap, a highly specific, nontoxic, cell-permeable small
      molecule, GSK-3betaFRB* binds to the ubiquitously expressed FKBP12 protein. This
      interaction stabilizes GSK-3betaFRB* and restores both protein levels and
      activity. C20-MaRap-mediated stabilization is rapidly reversed by the addition of
      an FKBP12 binding competitor molecule. This technology may be applied to a wide
      range of FRB*-tagged mouse genes while retaining their native transcriptional
      control. Inducible stabilization could be valuable for many developmental and
      physiological studies and for drug target validation.

PMID- 14690614
TI  - Nano-dynamics: engineering allostery via tandem duplication and turn energetics.

PMID- 14690615
TI  - Greener vaccine production with GM yeasts.

PMID- 14690616
TI  - The proteomics bottleneck: strategies for preliminary validation of potential
      biomarkers and drug targets.

PMID- 14690617
TI  - Mating antibody phage display with proteomics.

PMID- 14690618
TI  - High content screening applied to large-scale cell biology.

PMID- 14690619
TI  - Interrogating the transcriptome.

PMID- 14690620
TI  - Oligosaccharide synthesis by glycosynthases.

PMID- 14690621
TI  - Recent developments in ligase-mediated amplification and detection.

PMID- 14690623
TI  - Electronic lab notebooks -- a crossroads is passed.

PMID- 14690622
TI  - Transgenic microalgae as green cell-factories.

PMID- 14690624
TI  - Sending out the cytokine search party.

PMID- 14690625
TI  - Bacteria learn antibiotic resistance in the sludge.

PMID- 14690626
TI  - Drug designers seek a structural solution.

PMID- 14690629
TI  - Peter Goodfellow on how automation can aid innovation in the pharma industry.
      Interview by Joanna Owens.

PMID- 14690630
TI  - Inhibitory processes in the brain.

PMID- 14690631
TI  - HPLC-NMR-MS: past, present and future.

PMID- 14690632
TI  - Ion channels in drug discovery and development.

PMID- 14690633
TI  - Non-nicotinic neuropharmacological strategies for nicotine dependence: beyond
      bupropion.
AB  - Smoking is a major health problem and is propelled, at least in part, by the
      addictive properties of nicotine. Two types of pharmacological therapies have
      been approved for smoking cessation by the US Food and Drug Administration. The
      first therapy consists of nicotine replacement, substituting the nicotine from
      cigarettes with safer nicotine formulations. The second therapy is bupropion
      (Zyban), an atypical antidepressant, whose use has raised much debate as to how a
      non-nicotine-based agent can aid in smoking cessation. This review focuses on
      recent advances that could lead to the development of improved novel
      pharmacological treatments. These strategies focus on altering reward processes
      in the brain by modulating various neurotransmitter systems: the most promising
      include dopamine D(3) receptor antagonists, noradrenaline reuptake inhibitors,
      GABA(B) receptor agonists, metabotropic glutamate 5 (mGluR5) receptor
      antagonists, cannabinoid CB1 receptor antagonists, and corticotropin releasing
      factor (CRF) 1 receptor antagonists.

PMID- 14690634
TI  - Fluorescence readouts in HTS: no gain without pain?
AB  - Fluorescence-based detection technologies are frequently applied in biological
      testing, due to their unique advantages in setting up homogeneous, sensitive
      assays in miniaturized formats. However, the wide application of these readouts
      has highlighted challenges in reagent design and problems with interference from
      biological reagents and compounds. Here, we summarize the current application of
      fluorescence-based detection methodologies, focusing on the problems faced by
      assay developers and on solutions to reduce false positive and negative results
      in fluorescence-based HTS.

PMID- 14690635
TI  - Idiosyncratic toxicity: the role of toxicophores and bioactivation.
AB  - Drugs and chemicals can undergo enzyme-catalyzed bioactivation reactions within
      cellular systems, with the formation of reactive chemical species. These reactive
      metabolites can lead to thiol depletion, reversible protein modification
      (glutathionylation and nitration), further irreversible protein adduct formation
      and subsequent irreversible protein damage. The incorporation of potentially
      reactive chemical moieties - toxicophores - within new therapeutic agents should
      be limited. However, this cannot always be prevented, particularly when the
      structural feature responsible for toxicity is also responsible for the
      pharmacological efficacy. The identification and further knowledge of critical
      levels of thiol depletion and/or covalent modification of protein will aid in the
      development of new drugs. Importantly, the identification of drug-thiol
      conjugation should provide a warning of potential problems, yet not hinder the
      development of a potentially therapeutically useful drug.

PMID- 14690638
TI  - Nursing through the genetics lens: convergent thinking on education and
      professional development.

PMID- 14690639
TI  - Is our student portfolio valued?
AB  - A student portfolio was introduced for pre-registration nursing students at the
      University of Glamorgan in October 1997. The impetus for doing so was the
      recognised need to address:the 'theory-practice' divide;the need to provide nurse
      students with skills that will enable them to maintain the Professional Profile
      for registration purposes (). This article reports a research study evaluating
      the student portfolio. The main objectives of the evaluation were to investigate
      whether the portfolio addressed the perceived needs and to identify if students
      were experiencing potential benefits by using the portfolio. Semi-structured
      interviews and focus groups were conducted with students and staff about their
      usage and perceptions of the portfolio. These findings were used to inform the
      design of the questionnaire to investigate students' experiences of using the
      portfolio, and their views about its usefulness. The questionnaires (n=219)
      confirmed the impression that students are not making frequent use of the
      portfolio. Students mainly discussed sections relating to academic aspects of the
      course. The summative assessment (essays) section was discussed by the greatest
      proportion of students (51% n=108). More students (74%) felt that too little time
      was spent on the portfolio than any other aspect of the course. Although many
      students and staff appreciate the potential value of using the portfolio, it is
      not a requirement of the course and so tends not to be treated as a high
      priority. Many of the recommendations from this study focussed on ways of
      integrating the portfolio into the course in order to increase its use. The
      results of this study have informed the development of an All Wales Student
      Portfolio introduced in April 2002 (Welsh Assembly Government, 2002).

PMID- 14690640
TI  - Supporting nurses study: lay supporters and their work.
AB  - Nurse teachers are familiar with the study support arrangements made through the
      university, but what sorts of support do nurse learners obtain from lay sources?
      Within part time modes of study and particularly where students have multiple
      other commitments as professionals, partners and parents, the support obtained
      from friends and family may be critical to student success. This paper describes
      the work of lay supporters who assisted post registration, undergraduate nurses
      completing a Bachelor of Science degree in nursing studies by distance learning.
      Research was designed using grounded theory methodology and provided a
      substantive account of the ways in which students and lay supporters negotiated
      help. Data gathering centred upon 41 interviews with students, including 11 joint
      interviews with the student and a chosen lay supporter. Additionally 59 field
      observations and 24 tutorial observations were made where further student
      reported data was gathered about lay support. This study concluded that lay
      support contributed a significant amount to student progress but that academic
      staff remained largely unaware of the types and variety of help received there.
      Lay support in part determined the nature of requests for help that was then made
      to tutors.

PMID- 14690641
TI  - Student nurses' use of their interpersonal skills within clinical role-plays.
AB  - Heron's six-category intervention analysis is a component of many counselling
      courses and is used extensively by teachers of interpersonal skills within
      nursing curricula. In addition, researchers have used six-category intervention
      analysis as a theoretical framework for exploring nurses' perceptions of their
      interpersonal skills. This study aimed to advance previous research by using
      Heron's framework to analyse student nurses' actual skills, as deployed in
      clinical role-plays, and then to compare them to earlier findings. Analysis of
      the data produced the following rank order of interventions based on Heron's
      framework: catalytic, prescriptive, supportive, informative, confronting and
      cathartic. The findings both challenge and support previous findings on nurses'
      perceptions of their interpersonal skills. The paper discusses these findings and
      their implications for clinical practice.

PMID- 14690642
TI  - Mentor preparation: reasons for undertaking the course and expectations of the
      candidates.
AB  - This study sought to explore the assumption that potential participants to do the
      English National Board Teaching and Assessing in Clinical Practice course (ENB
      998) were motivated to undertake the programme by a commitment to become a
      mentor. Two cohorts of students (n=127) were invited to complete a specifically
      constructed questionnaire and the majority responded (n=115, response rate
      90.6%). The results were analysed using SPSS v10 [SPSS Inc., SPSS for Windows,
      1999]. The findings suggest that commitment to undertaking the role of the mentor
      was not the only motivator for those undertaking this programme of preparation.
      Fifty-eight percentage (n=67) identified enhanced job prospects as a benefit of
      the course. Recommendations are made that the course should not be universally
      required for promotion and that it be, solely, identified as a course for mentor
      preparation. It is also recognised that this approach requires a national
      movement in this area if it is to succeed.

PMID- 14690643
TI  - Concept mapping for meaningful learning.
AB  - The complexity of teaching, learning and assessment strategies remains a problem
      in nurse education especially with the changes in new curricula. This article
      explains one solution, which was considered and explored prior to implementation
      for the assessment of an inquiry-based module in nurse education. The overall aim
      for selecting this method of assessment was to provide consolidation of prior
      learning from the core content of the module and to give the students an
      opportunity to gain further, wide and varied knowledge on a number of concepts in
      a short period. Concept mapping has proved to be one of the most challenging
      learning experiences for nursing students. It has been identified as a
      stimulating learning and assessing tool as predominantly acknowledged over the
      last year, by nursing students on the Inquiry-Based Learning (IBL) BSc and Dip HE
      nursing education programmes, and also nurse educators who have the
      responsibility of facilitating the learners.

PMID- 14690644
TI  - Information-seeking behaviour of nurse teachers in a school of health studies: a
      soft systems analysis.
AB  - AIM: This paper reports a small-scale study, undertaken as part of a higher
      degree, which aims to explore the information-seeking behaviour of a group of
      lecturers, based on one site, delivering a nursing and midwifery curriculum in
      the School of Health Studies of a higher education institution. METHODOLOGY:
      Checkland's [System thinking, System practice, Wiley, Chichester, 1981] soft
      systems methodology (SSM) was used as a theoretical model both to derive deeper
      insights into the survey data and suggest enhancements to this aspect of teacher
      activity. To obtain statistical data a survey design was employed, research
      methods including postal questionnaires complemented by selected interviews and a
      small amount of informal observation. RESULTS: Findings showed that, in order to
      access information, lecturers were most likely to access the School libraries,
      the Internet, advice from colleagues and their personal collections. Refereed
      journals were the top-ranked information resource with professional studies and
      research cited as the most sought after topics. Lecturers mentioned the role of
      library staff as integral to the information-seeking process. Main problems
      included their variable literature searching skills and time pressures. The
      methodology identified several features related to the information-seeking
      behaviour of lecturers that has resulted in an improved training programme for
      lecturers and prompted enhancements to the School's current awareness service and
      Library Intranet pages. CONCLUSIONS: The use of SSM for this study allowed the
      analysis of a broad and complex situation which enabled key changes to the
      information-seeking behaviour of lecturers to be implemented.

PMID- 14690645
TI  - Qualifying from the pre-registration nurse diploma course: the demand for career
      guidance.
AB  - A previous paper in Nurse Education Today [Marsland, L. (1996) Career guidance
      for student nurses: an unmet need, Vol. 16, No. 1, p. 10] presented research
      about career guidance received during nurse education by 1015 Registered General
      Nurses (RGNs) who qualified in 1990/1991. The findings revealed a substantial
      unmet need for guidance amongst this group, especially in relation to discussions
      about individual career planning. The paper argued that the greater variety of
      training experiences incorporated into the Project 2000 diploma course
      curriculum, plus the opportunity in some colleges to defer branch selection until
      after the common foundation programme, would increase rather than decrease the
      need for pre-registration guidance. The research presented in this subsequent
      paper investigates career guidance received by a cohort of adult branch nurses
      who qualified from the nurse diploma course in 1997/1998. Similarities and
      differences between the guidance experiences of the two cohorts are discussed,
      and deficits experienced by the diploma course nurses identified.

PMID- 14690651
TI  - Educational programs of IAOMS.

PMID- 14690652
TI  - The quantification of angiogenesis in relation to metastasis in oral cancer: a
      review.
AB  - Tumours need vessels to grow into clinically significant dimensions, and to
      metastasize. Varying results have been reported for the relation between
      angiogenic activity in oral carcinomas, and the occurrence of metastasis.
      Quantification of microvessels in tissue sections is mostly used to assess
      angiogenesis, but appears subject to biases as reflected in contradicting
      reports. Especially the choice of immunohistochemical staining technique appears
      pivotal. Although microvessel density measurements (MVD) appear promising for
      other tumour types, in oral carcinomas no unambiguous relation could be
      established. Furthermore, MVD assessment appears more elaborate than expected.
      New, more time efficient techniques may replace MVD as we know it.

PMID- 14690653
TI  - Temporomandibular joint discectomy for treatment of unilateral internal
      derangements--a 5 year follow-up evaluation.
AB  - Fifteen fully dentated patients with pain and functional impairment due to
      unilateral temporomandibular joint disc displacements, who had undergone
      unsuccessful nonsurgical treatment, were treated with discectomies without any
      disc substitutes and followed for 5 years. Their contralateral temporomandibular
      joints were without any clinical or radiographic evidence of pathology.
      Functional pain was reduced and mandible opening ability increased although a
      full range of motion was not restored. This study verified that discectomies can
      reduce pain on chewing, however, pain at rest was not significantly changed. At 5
      years 87% of the patients fulfilled the criteria for a successful result of TMJ
      surgery.

PMID- 14690654
TI  - The diagnostic value of ultrasonography in the detection of orbital floor
      fractures with a curved array transducer.
AB  - The aim of the study was to investigate the diagnostic value of ultrasonography
      (US) in orbital floor fractures and orbital rim fractures with a curved array
      scanner. Over a period of 10 months, 60 patients with an orbital trauma have been
      investigated. Orbital trauma was defined by clinical and ophthalmologic
      investigation. Computed tomography (CT) was used as the reference method to
      evaluate the diagnostic value of US in the determination of an orbital floor
      fracture and was performed by a well-experienced radiologist. Coronal and
      sagittal images were made. The US investigation was performed with a 7.5 MHz
      curved array transducer.The US investigation of the infraorbital rim showed a
      sensitivity of 94% and a specificity of 92% with a diagnostic accuracy of 92%.
      The positive predictive value (PPV) reached 91% and the negative predictive value
      (NPV) reached 92%, while the US investigation of the orbital floor showed a
      sensitivity of 95% and a specificity of 100% with a diagnostic accuracy of 98%.
      PPV reached 100% and NPV reached 77%. Ultrasonography is a cost-effective and
      widely available method without disadvantages such as radiation exposure. The
      results in the current study imply that ultrasonography can be used as an
      alternative method in the investigation of orbital floor fractures.

PMID- 14690655
TI  - Combined space management through Delaire/Joos osteotomy and postoperative
      orthodontic treatment. A retrospective longitudinal study.
AB  - The diagnostic records of all patients who had undergone Delaire/Joos osteotomy
      with mandibular setback at the Muenster University Hospital (period 1995-2000,
      n=22) were used for space management evaluation in the context of combined
      surgical-orthodontic treatment.Twenty-eight dental spaces were present prior to
      the start of treatment and 14 were created by extracting teeth as a pretreatment
      measure. In two patients, unilateral setback was performed according to
      Obwegeser/Dal Pont. Thus, 42 tooth-bounded spaces were present at the time of
      Delaire/Joos osteotomy with mandibular setback, most of them in the first molar
      region, followed by the second premolar region. A significant space reduction was
      achieved by the surgical intervention, but not by the subsequent orthodontic
      treatment. The best results with respect to complete space closure by
      orthognathic surgery/orthodontic treatment without the need for subsequent
      prosthetic rehabilitation were recorded in the second premolar region. In the
      absence of spaces and with a similar long-term prognosis for all potentially
      extractable teeth and adequate space for the necessary surgical repositioning,
      the second premolars should therefore be regarded as the 'extraction teeth of
      choice' for mandibular setback within the context of Delaire/Joos osteotomy.

PMID- 14690656
TI  - Adenoid cystic carcinoma of the head and neck--a 20 years experience.
AB  - In this retrospective study we give a clinical review of our experience with
      adenoid cystic carcinoma (ACC) and compare our results with those reported in the
      literature. Between 1981 and 2000, 74 patients with this disease were treated at
      our department. Complete resection was reached in 45 cases. Fourteen patients
      received postoperative radiation. Local control rates at 5, 10 and 15 years were
      64%, 56% and 52% with a mean local control time of 11.1 years. Tumour size (P<or=
      0.001), perineural invasion (P<or= 0.001) and margin status (P<or= 0.001) showed
      significant influence on local control. Statistically, we were not able to
      demonstrate a positive effect for postoperative radiation. Distant control rates
      at 5, 10 and 15 years were 72%, 62% and 59% with a mean distant control time of
      14.4 years. Distant failure was diagnosed in lungs and bones and occurred
      independently of local treatment outcome. Overall survival rates at 5, 10 and 15
      years were 71%, 54% and 37% with a mean overall survival of 11.2 years.
      Recurrence-free survival rates at 5, 10 and 15 years were 57%, 45% and 37% with a
      mean recurrence-free survival of 9.1 years. The survival rates at 5, 10 and 15
      years after diagnosis of tumour progression were 35%, 15% and 0% with a mean
      survival time of 4.7 years. Our results provide insights to the unusual nature of
      ACC, which may be useful for making clinical decisions. However, prospective
      randomized multicentric studies are needed to define the optimal treatment for
      ACC with special regard to adjuvant treatment modalities.

PMID- 14690657
TI  - Periodontal healing after mandibular third molar surgery--A comparison of
      distolingual alveolectomy and tooth division techniques.
AB  - The purpose of this study was to compare the periodontal healing of mandibular
      second molars after the removal of impacted mandibular third molars using
      distolingual alveolectomy and tooth division techniques. A total of 120
      consecutive healthy patients who presented with bilaterally impacted mandibular
      third molars were included in this study. The same operator removed the impacted
      third molars on both sides in all patients. The third molar on one side was
      removed by distolingual alveolectomy using a chisel, whereas the contralateral
      tooth was removed by the tooth division technique using burs. Attachment level,
      periodontal pocket depth and bone healing distal to the mandibular second molars
      were assessed at 7 days, 3 months and 6 months after surgery. The results showed
      better periodontal healing and bone healing when distolingual alveolectomy was
      employed, especially in the removal of deeply impacted mandibular third molars.

PMID- 14690658
TI  - Preliminary investigation into the effects of electrical stimulation on
      mandibular distraction osteogenesis in goats.
AB  - Craniofacial distraction osteogenesis (DO) was found to be a procedure with low
      preoperative and postoperative morbidity. Direct current electrical stimulation
      is used clinically to treat different orthopaedic problems. It provided a
      significant increase in new-bone formation, and a higher mechanical strength of
      healing. The purpose of this study was to test the effect of electric current on
      distraction osteogenesis and to establish the best period to apply an electric
      current during the different distraction phases. Twelve healthy adult goats were
      subjected to a vertical osteotomy in the symphyseal area. A distraction device
      was fixed to the bone. Animals were divided into two groups, Group I (three
      goats) and group II (nine goats). In group I, the device was activated 1mm per
      day for 10 days; while in group II, the device was activated 1mm per day for 10
      days with the application of direct electric current stimulation of 10 microA
      either during the first 3 days of latency in a continuous mode (ESL group), or
      during the first 3 days of the activation period in a continuous mode (ESA
      group); or during the first 3 days of the consolidation period in a continuous
      mode (ESC group). After the activation period was completed, the distraction
      device left in place for additional 15 days for bone consolidation in all
      animals. Animals were then sacrificed, the mandible was harvested, and the
      distracted areas were removed and processed for mechanical and histological
      studies. The results of this study suggested that direct current electrical
      stimulation display synergism on mandibular distraction when this stimulation
      applied to the distraction zone during activation or consolidation periods.

PMID- 14690659
TI  - Mandibular reconstruction: a histological and histomorphometric study on the use
      of autogenous scaffolds, particulate cortico-cancellous bone grafts and platelet
      rich plasma in goats.
AB  - Twenty-eight goats underwent a continuity resection of the mandibular angle. In
      all goats primary reconstruction was carried out using specially designed pre
      shaped osteosynthesis plates and monocortical screws. The original cortical
      scaffold was used to bridge the defect, filled with an autogenous particulate
      bone graft in 14 goats, whereas platelet-rich-plasma (PRP) was added in another
      14 goats. Both groups were divided in three subgroups that were sacrificed after
      3, 6 and 12 weeks. Histological and histomorphometric evaluation revealed that
      the use of PRP enhanced the bone healing considerably. This effect was
      statistically significant and particularly visible in the 6 and 12 weeks' groups

PMID- 14690660
TI  - Effect of platelet-rich plasma on bone regeneration in autogenous bone graft.
AB  - In this study, we evaluated the effect of platelet-rich plasma (PRP) on bone
      regeneration in an autogenous bone graft in a canine model. The mandibular
      premolar teeth had been bilaterally extracted previously, and the ridges had been
      allowed to heal for 3 months. After this period, continuity resection was
      performed on both sides of the mandible. One defect (the PRP group) was
      reconstructed with the original particulate bone mixed with PRP. As a control,
      the contralateral defect (non-PRP group) was reconstructed with the original
      particulate bone alone. Biopsies after 6 weeks showed lower levels of bone
      formation in the PRP group than in the non-PRP group, and fluorescence microscopy
      revealed a delay in the remodelling of grafts loaded with PRP. These findings
      suggest that the addition of PRP does not appear to enhance new bone formation in
      autogenous bone grafts.

PMID- 14690661
TI  - Influence of platelet-rich plasma (PRP) on osteogenic differentiation of rat bone
      marrow stromal cells. An in vitro study.
AB  - Recent clinical reports suggest that the application of an autologous blood
      plasma enriched with thrombocytes by centrifugal concentration (platelet-rich
      plasma: PRP) can enhance the formation of new bone. There are very fewin vitro or
      in vivo studies published on the efficiency of PRP. In this project a three
      dimensional cell culture system was used to compare PRP and rhBMP-2 in vitro.
      Marrow derived bone forming cells from Spraque-Dawley (SD) rats were seeded on
      porous collagenous carriers (d=5mm, h=3mm) at a density of 4 x 10(4)
      cells/carrier and exposed to different concentrations of PRP (platelet counts
      from 2.5 x 10(8)-1.6 x 10(7) platelets/culture), rhBMP-2 (300 ng) or plasma poor
      in thrombocytes (platelet-poor plasma, PPP). Cultures without additional
      supplements were used as controls. During a culture period of 21 days cell
      proliferation, alkaline phosphatase activity (ALP) and calcium content (days 18,
      21) were measured in 3 day intervals.PRP showed a dose dependent stimulation of
      cell proliferation, while reducing ALP activity and calcium deposition in the
      culture. BMP-2 led to an opposite cell response and induced the highest ALP
      activity and mineral deposition. These data suggest that PRP inhibited osteogenic
      differentiation of marrow derived pre-osteoblasts in a dose dependent manner. PRP
      is not a substitute for BMP-2 in osteogenic induction.

PMID- 14690662
TI  - Human papillomavirus type 16 and 18 DNA in oral squamous cell carcinoma and
      normal mucosa.
AB  - The aim of this study was to ascertain the prevalence of HPV 16/18 DNA in oral
      squamous cell carcinoma (OSCC) vs. normal oral mucosa, and to correlate the
      virologic data with other factors obtained from the patients' records. One
      hundred and thirteen paraffin embedded tissue samples (73 OSCC and 40 normal oral
      mucosa) were studied using HPV type specific primer-mediated polymerase chain
      reaction (PCR). Seventy-four per cent (54/73) of OSCC and 55% (22/44) of normal
      oral mucosa were positive for HPV 16/18 DNA. Statistical analysis indicated there
      was a significant difference between HPV16/18 positive OSCC vs. normal oral
      mucosa (P=0.040), and that age (<60 years) and gender (male) were correlated with
      the presence of HPV16/18 in the tumour. No significant association was found
      between the presence of HPV and other risk factors, including tobacco use,
      alcohol use, tumour location, histologic grade or TNM staging. We found a
      significant association of HPV16/18 with oral squamous cell carcinoma. Also,
      HPV16/18 is a co-factor in oral carcinogenesis, particularly in male patients and
      patients under the sixth decade. In addition, we found that HPV infection is a
      common event in the normal oral mucosa.

PMID- 14690663
TI  - Cell proliferation and tumour suppressor gene expression in iodine unstained area
      surrounding oral squamous cell carcinoma.
AB  - The purpose of this study was to investigate the relationship between epithelial
      dysplasia unstained with iodine and the expression of proliferating cell nuclear
      antigen (PCNA) and/or tumour suppressor gene (p53) and the existence of glycogen.
      Thirty cases of squamous cell carcinomas arising from the buccal mucosa and floor
      of the mouth were examined. Iodine unstained areas were diagnosed
      histopathologically as mild, moderate or severe epithelial dysplasia. Normal oral
      mucosa stained with iodine was used as a control group. There was no
      histochemical difference in the distribution or ratio of PAS-positive cells
      between the control and the mild epithelial dysplasia groups, however PAS stained
      areas of the moderate and the severe dysplasia groups were significantly
      decreased. Ultrastructurally, glycogen granules were not recognized in the
      moderate or severe dysplastic epithelia. Immunoreactive ratios of PCNA and p53 in
      the moderate and severe dysplastic groups were significantly higher than those of
      the control and the mild dysplasia groups. The positive ratio of PCNA was higher
      than that of p53, although the immunostaining patterns of PCNA- and p53-positive
      cells were quite similar. These results suggest that mild dysplastic epithelia
      that are stained with iodine may be in the category of normal epithelia, whereas
      both moderate and severe dysplasia that are un-stained with iodine may be
      suspected of malignant lesions.

PMID- 14690664
TI  - Autologous fibrin glue with growth factors in reconstructive maxillofacial
      surgery.
AB  - The aim of this paper was to describe a method for the preparation of autologous
      fibrin glue with platelet growth factors and to report its use with particulate
      cancellous bone in reconstructive maxillofacial surgery. The fibrin glue is a two
      component glue, where the one component is a concentrated fibrinogen solution
      with platelet growth factors and the other component is a thrombin solution. Both
      components were produced from the patients own blood, thus making the glue
      entirely autologous. The glue was prepared from platelet rich plasma separated
      from 200 ml of the patient's blood prior to the operation. The fibrinogen in the
      glue was precipitated from the platelet rich plasma by ethanol precipitation at
      low temperature and separated together with the platelets by centrifugation.
      Raising the temperature to 37 degrees C redissolved the precipitate. The thrombin
      solution in the glue was produced from prothrombin precipitated from 10 ml of the
      platelet rich plasma by lowering the pH and the ionic strength. The precipitate
      was separated by centrifugation and dissolved in a calcium ion solution.
      Increasing the pH to neutral value induced activation to thrombin. Preparation of
      the fibrin glue was performed in the blood bank within 60 to 90 min with the use
      of standard equipment. The outcome from 200 ml of blood was approximately 8 ml of
      fibrin glue: 6 ml fibrinogen to be coagulated with 2 ml of thrombin. The glue had
      a fibrinogen concentration of approximately 12 times the value in platelet rich
      plasma and the concentration of growth factors was approximately eight times the
      value in platelet rich plasma. We have used this glue successfully with
      particulate bone grafts for reconstructive purposes within the oral and
      maxillofacial field. It might as well be applied to other surgical areas.
      Whenever larger amount of the glue will be needed, a whole unit of blood may be
      taken from the patient, and the red cells re-transfused to the patient during or
      after the operation.

PMID- 14690665
TI  - Ocular palsy following Le Fort 1 osteotomy: a case report.
AB  - A 33-year-old female patient developed an ipsilateral sixth nerve palsy and
      partial third nerve palsy following a Le Fort 1 osteotomy. Complete resolution
      occurred at 10 weeks. The likely mechanism of injury secondary to pterygo
      maxillary dysjunction is highlighted, with description of the relevant anatomy.
      Previous cases of ocular motility complications following Le Fort 1 osteotomy are
      discussed. We recommend that significant care be taken in osteotome placement in
      the pterygo-maxillary fissure, particularly in those prone to unpredicted
      fractures such as older patients, or where the anatomy is congenitally abnormal
      or altered by previous surgery.

PMID- 14690666
TI  - An adult case of oral infection with Kingella kingae.
AB  - An exceptional case of microbiologically confirmed oral infection with Kingella
      kingae in an immunocompetent adult (30-year-old woman) is presented and the
      pathogenesis is discussed and related to known literature data.K. kingae is a
      rather common but yet relatively unknown commensal corroding bacterium from the
      oro- and nasopharynx in healthy children, which might turn into a human pathogen
      causing osteomyelitis, arthritis, spondylitis, endocarditis and intervertebral
      diskitis in young children and rarely endocarditis, septic arthritis, meningitis,
      epiglottitis, diskitis and bacteraemia in adults. Sofar K. kingae associated
      stomatitis was reported in children and a few adults, however, with concomitant
      herpes simplex virus infections, and without microbiological confirmation. In the
      described case no viral infection was found. The proven K. kingae stomatitis
      represents an extension of the pathogenic spectrum and suggests that the breach
      of the oral mucosal barrier can be caused by the bacterial pathogen itself.
      Whether a concomitant viral infection is necessary forK. kingae to actually
      invade the bloodstream remains to be considered.

PMID- 14690668
TI  - Immunophenotype of the juxtaoral organ.

PMID- 14690669
TI  - Measures of anxiety: is there a difference in their ability to predict
      functioning at three-month follow-up among pain patients?
AB  - Independent investigators have found that pain is related to health anxiety,
      trait anxiety, pain-related anxiety, and anxiety sensitivity. To date, the
      relationship among these anxiety-related constructs has not been studied directly
      and little is known about their relative ability to predict adjustment to pain
      over time. This paper presents longitudinal data from measures given to 227
      musculoskeletal pain patients. Patients were asked at the time of their first
      visit (T1) to a physiotherapy clinic to complete a questionnaire package
      including measures of these different forms of anxiety as well as pain severity,
      disability, negative affect, and perceived control. Approximately 3 months later
      (T2), 50% of patients responded to these same questionnaires. Results showed that
      correlations among the anxiety measures at T1 ranged from 0.35 to 0.56. Using
      multiple regression analyses, measures of T1 anxiety were each examined for their
      ability to predict unique variance in disability, negative affect, and
      perceptions of control measured at T1 and T2. At T1, after controlling for pain
      severity and other measures of anxiety, pain-related anxiety uniquely predicted
      both disability and negative affect, trait anxiety uniquely predicted negative
      affect and perceptions of control, and anxiety sensitivity uniquely predicted
      negative affect. At T2, after controlling for pain severity, other measures of
      anxiety and each respective measure of functioning at T1, health anxiety uniquely
      predicted disability and negative affect, although anxiety sensitivity also
      uniquely contributed to the prediction of negative affect. It is concluded that
      the importance of various forms of anxiety is dependent on the timeframe and
      outcome examined. Clinical implications of the findings as well as directions for
      future research are discussed.

PMID- 14690670
TI  - When pain is not fully explained by organic lesion: a psychiatric perspective on
      chronic pain patients.
AB  - Recent literature demonstrates the relationship between psychopathology and
      medically unexplained pain, even if the results of several studies show a high
      degree of variability. The present study was planned with the aim of analysing
      both the possible relationship between the level (low/high) of organicity and the
      presence of psychopathology, and the degree to which these differences are
      related to methodological problems. Between 1998 and 2000, four hundred and
      thirty six consecutive patients seen at the Pisa Pain Therapy and Palliative Care
      Unit were requested to fill in a questionnaire, the GHQ-12, to screen the
      subjects probably with (GHQ-12>3) or without (GHQ-12</=3) psychopathology. All
      the patients scoring above the GHQ-12 threshold (score of 3), and a randomised
      sample of those scoring below the GHQ-12 threshold, were included in the study.
      These patients were then interviewed using three different instruments: the Mini
      International Neuropsychiatric Interview (MINI) for a standardised psychiatric
      diagnosis, the Semistructured Interview for Depression (SID) for the
      characterisation of temperament, and the Italian Pain Questionnaire (IPQ) for the
      evaluation of pain. Our results suggest that Somatisation Disorders are more
      frequent in the medically unexplained pain group than in the medically explained
      pain group, whereas the other psychiatric disorders have a similar prevalence in
      the two pain groups. Mood and anxiety disorders are correlated with high scores
      on GHQ-12 and medically explained pain has a higher prevalence of GHQ-12>3 than
      the medically unexplained pain group. These results confirm that methodology is
      an important factor that could modify results in psychiatric research. Both
      medically unexplained pain and the presence of psychopathology are significantly
      correlated with sex, and age: females and young patients have a higher prevalence
      of psychopathology and of medically unexplained pain. Our results suggest that in
      the correlation between the low organicity of pain and psychopathology, the age
      and sex play a relevant role.

PMID- 14690671
TI  - Impaired health status, sleep disorders, and pain in the craniomandibular and
      cervical spinal regions.
AB  - This study investigated the relationship between health status (i.e., physical
      well-being and quality of life), sleep disorders (e.g., insomnia, sleep-related
      depression and anxiety), and musculoskeletal pain in the craniomandibular and
      cervical spinal regions. The number of painful body areas below the cervical
      spine (i.e., widespread pain) was also taken into account. Two questionnaires,
      viz., the RAND 36-item Health Survey Questionnaire and the Dutch Sleep Disorders
      Questionnaire (SDQ), were administered to 103 persons who could unequivocally be
      classified into one of four mutually exclusive groups: No pain, craniomandibular
      pain (CMP), cervical spinal pain (CSP), and both CMP and CSP. Body drawings were
      used for the self-report of widespread pain. Multivariate analysis of variance
      showed effects of gender, group, and widespread pain on the questionnaire scales;
      not of age. As shown by univariate analysis of variance, men suffered more from
      sleep apnea than did women. No other gender differences were found. Simple
      contrast analyses following univariate analyses of the group and widespread pain
      effects showed that, in general, more questionnaire scales, both of the RAND-36
      and of the SDQ, reached statistical significance with an increase in the number
      of painful areas. It was concluded that both musculoskeletal pain in the
      trigemino-cervical area and widespread body pain are associated with an increased
      impairment of health status. Also, sleep disorders are frequently found in
      patients with chronic pain in the craniomandibular and cervical spinal regions as
      well as in patients with widespread pain. The more painful areas there are, the
      likelier it is that sleep disorders are present.

PMID- 14690672
TI  - The tridimensional personality theory and pain: harm avoidance and reward
      dependence traits correlate with pain perception in healthy volunteers.
AB  - The aim of the present study was to examine the possible role of personality
      traits in determining the variability of pain perception among individuals. More
      specifically, it was intended to test whether or not the three personality
      dimensions suggested by Cloninger in 1987 - mainly harm avoidance (HA), but also
      reward dependence (RD), and novelty seeking (NS), can predict interpersonal
      differences in responsiveness to experimental pain. Seventy healthy volunteers
      participated in the study. Their personality traits were evaluated through
      Cloninger's tridimensional personality questionnaire (TPQ). Pain threshold
      (latency to pain onset), pain magnitude (VAS), and pain tolerance (time to
      withdrawal) were measured by using the cold pressor test. Bonferroni-adjusted
      correlations were found between HA and the pain parameters as follows: a negative
      correlation between HA and threshold (rho=-0.297, P(adj)=0.039); no significant
      correlation between HA and tolerance (rho=-0.219, P(adj)=0.207); and a trend for
      a positive correlation between HA and VAS (rho=0.266, P(adj)=0.081). Possible
      correlations between pain perception and the various possible combinations of
      high and low scoring for each of the three traits were also investigated.
      Correlations were found only for the combinations of high/low HA and high/low RD.
      The low HA/low RD combination demonstrated the lowest responsiveness to pain (VAS
      65.2+/-21.4; tolerance 107.6+/-71.8 s), whereas the high HA/low RD combination
      was correlated with the highest responsiveness (VAS 83.3+/-10.8; tolerance 30.8+/
      28.4 s). The results indicate that HA personality trait correlates best with pain
      responsiveness. As such, a high HA are likely to predict a heightened pain
      response. RD may modify this pattern. The possible relevant behavioral and neuro
      chemical mechanisms are discussed.

PMID- 14690673
TI  - Evidence for a direct relationship between cognitive and physical change during
      an education intervention in people with chronic low back pain.
AB  - BACKGROUND: Unhelpful pain cognitions of patients with chronic low back pain
      (LBP) may limit physical performance and undermine physical assessment. It is not
      known whether a direct relationship exists between pain cognitions and physical
      performance. AIMS: To determine if a relationship exists between change in pain
      cognitions and change in physical performance when chronic LBP patients
      participate in a single one-to-one education intervention during which they have
      no opportunity to be active. METHODS: In a quasi-experiment using a convenience
      sample, moderately disabled chronic LBP patients (n=121) participated in a one-to
      one education session about either lumbar spine physiology or pain physiology.
      Multiple regression analysis evaluated the relationship between change in pain
      cognitions measured by the survey of pain attitudes (SOPA) and the pain
      catastrophising scale (PCS) and change in physical performance, measured by the
      straight leg raise (SLR) and standing forward bending range. RESULTS: There was a
      strong relationship between cognitive change and change in straight leg raise
      (SLR) and forward bending (r=0.88 and 0.79, respectively, P<0.01), mostly
      explained by change in the conviction that pain means tissue damage and
      catastrophising. CONCLUSIONS: Change in pain cognitions is associated with change
      in physical performance, even when there is no opportunity to be physically
      active. Unhelpful pain cognitions should be considered when interpreting physical
      assessments.

PMID- 14690674
TI  - The course of non-malignant chronic pain: a 12-year follow-up of a cohort from
      the general population.
AB  - The high prevalence of chronic pain (duration >3 months) reported from different
      populations indicates a public health problem. Knowledge of the long-term course
      of chronic non-malignant pain is incomplete and scarce. This paper describes a
      follow-up of a cohort recruited from a survey in the general population. The
      cohort (n=214) consisted initially of individuals with widespread or located
      (neck-shoulder) pain or without chronic pain. The individuals were initially
      examined and replied to questionnaires on pain, social factors, lifestyle,
      medication and health care after two and 12 years. The deaths during the period
      were obtained from the population register. Complete data exist for 77% of the
      eligible individuals. After 12 years one-third of the individuals initially
      without pain reported chronic pain, and among those with initial chronic pain 85%
      still reported chronic pain. The number of painful areas was the strongest
      predictor of chronic pain 12 years later (OR 15.8; >3 locations vs. 0) whereas a
      social factor (having a close friend) decreased the risk (OR 0.44). The onset of
      chronic pain during the same period was related to the physical workload (work
      with bent positions; OR 5.31; yes vs. no). Mortality was significantly higher in
      the group initially reporting widespread pain compared with the other groups. The
      chronicity of widespread chronic pain supports early and intense intervention
      among individuals with located pain. The association between chronic widespread
      pain and increased mortality needs further investigation but may deepen the view
      of chronic pain as a public health problem.

PMID- 14690675
TI  - Clinical study of chronic pain in hereditary myopathies.
AB  - In the field of neuromuscular diseases, pain and its management remain
      imperfectly understood and described. We study 68 unselected, consecutive adult
      patients attending a multidisciplinary consultation for hereditary myopathy.
      Forty-six (67%) were suffering from chronic pain. Pain was assessed with self
      report questionnaire and a standardized clinical evaluation. Mean duration of the
      pain was 7.2+/-8.9 years, and multiple body sites were involved in 91% of cases.
      Usual pain intensity (Visual Analogue Scale 0-100) was moderate (39.5+/-26.2).
      For 42 patients (91%) the principal cause of the pain was of muscular origin,
      with frequent features of myofascial pain syndromes (MPS, 50%) and fibromyalgia
      (FMS, 26%). Pain was the major complaint for 6.3% of the patients. Pain
      management was essentially based on physiotherapy. Only a minority of patients
      (38%) has an appropriate drug treatment. Common analgesics appeared to be very
      effective in these patients.

PMID- 14690676
TI  - Comorbidity of pain problems and depressive symptoms in young women: results from
      a cross-sectional survey among women aged 15-24 in Hungary.
AB  - Frequent headaches and musculoskeletal pain problems were assessed as part of a
      cross-sectional health survey in a representative sample of 3615 young Hungarian
      women, aged 15-24 (mean age: 19.0 years). The representative sample was obtained
      by a multilevel stratified sampling procedure based on national statistical data,
      the refusal rate was 6%. Depressive symptomatology was assessed as well using the
      shortened form of the Beck Depression Inventory. The overall prevalence of
      frequent headaches was 43.8% in the sample, 25.8% of the investigated population
      reported chronic musculoskeletal pain problems. The co-prevalence rate of
      depression was significantly higher in the group of interviewees reporting pain
      problems, 11.2% in the group indicating frequent headaches (chi(2)=53.1,
      p<0.001), 10.3% in the group reporting musculoskeletal pain problems
      (chi(2)=12.4, p<0.001). In contrast, the prevalence of depressive symptomatology
      was 4.6% and 6.6% in the subgroups denying frequent headaches and musculoskeletal
      pain, respectively. The prevalence of chronic pain problems decreased with higher
      age, increased with the smaller size of residence and was lower in the non
      student employment group, however, these differences across sociodemographic
      variables did not remain significant if tested by a multivariate logistic
      regression analysis. The high co-prevalence rates of depression in interviewees
      reporting chronic pain problem draws attention to the development of such
      secondary health problems and underscores the importance of early prevention.
      Epidemiological studies provide data for the better planning and management of
      prevention programs.

PMID- 14690677
TI  - Neck flexor muscle fatigue is side specific in patients with unilateral neck
      pain.
AB  - Despite the evidence of greater fatigability of the cervical flexor muscles in
      neck pain patients, the effect of unilaterality of neck pain on muscle fatigue
      has not been investigated. This study compared myoelectric manifestations of
      sternocleidomastoid (SCM) and anterior scalene (AS) muscle fatigue between the
      painful and non-painful sides in patients with chronic unilateral neck pain.
      Myoelectric signals were recorded from the sternal head of SCM and the AS muscles
      bilaterally during sub-maximal isometric cervical flexion contractions at 25% and
      50% of the maximum voluntary contraction (MVC). The time course of the mean power
      frequency, average rectified value and conduction velocity of the
      electromyographic signals were calculated to quantify myoelectric manifestations
      of muscle fatigue. Results revealed greater estimates of the initial value and
      slope of the mean frequency for both the SCM and AS muscles on the side of the
      patient's neck pain at 25% and 50% of MVC. These results indicate greater
      myoelectric manifestations of muscle fatigue of the superficial cervical flexor
      muscles ipsilateral to the side of pain. This suggests a specificity of the
      effect of pain on muscle function and hence the need for specificity of
      therapeutic exercise in the management of neck pain patients.

PMID- 14690678
TI  - Psychosocial experiences among primary care patients with and without
      musculoskeletal pain.
AB  - We examined differences in demographic/financial characteristics, burnout, job
      demands/control/strain and symptoms of depression as measured by GHQ among
      primary care patients with (n=838) and without pain (n=135). In addition, we
      examined factors associated with the presence of pain by means of logistic
      regression analyses among all participants, and inter-relations between
      demographic/financial/pain/health variables, symptoms of depression, burnout, and
      disability by means of multivariate regression analyses among pain patients. The
      patients completed a questionnaire about areas such as job strain and burnout.
      The design was cross-sectional and data were collected during 15 consecutive
      days. The univariate analyses showed that pain patients, compared with patients
      without pain, were more often females, older, divorced, foreign-born, had been
      more often on sick-leave, were more preoccupied with how to make ends meet and
      had greater difficulties in raising a reasonable sum of money within a specific
      period of time. In addition, they had greater levels of depression symptoms,
      burnout, and job strain. However, the multivariate analyses showed that symptoms
      of depression and burnout were more associated with such variables as sick-leave
      and divorce than by pain parameters. The logistic regression revealed that the
      presence of pain was associated with female gender, sick-leave, and high levels
      of job strain and mean total burnout. Finally, pain patients had a severe
      clinical situation in terms of, for example, constant, intense, and prolonged
      pain, and experienced a high degree of disability due to pain. We corroborated
      previous findings and may have provided new insights into the experiences of pain
      patients that may be of importance when considering intervention. Although we
      pointed to some important factors associated with pain, symptoms of depression
      and burnout, much of their variation remains to be explained. Thus, further
      research appears necessary, not least concerning the role of burnout as an
      antecedent to pain.

PMID- 14690679
TI  - Radiative decay engineering 3. Surface plasmon-coupled directional emission.
AB  - A new method of fluorescence detection that promises to increase sensitivity by
      20- to 1000-fold is described. This method will also decrease the contribution of
      sample autofluorescence to the detected signal. The method depends on the
      coupling of excited fluorophores with the surface plasmon resonance present in
      thin metal films, typically silver and gold. The phenomenon of surface plasmon
      coupled emission (SPCE) occurs for fluorophores 20-250 nm from the metal surface,
      allowing detection of fluorophores over substantial distances beyond the metal
      sample interface. SPCE depends on interactions of the excited fluorophore with
      the metal surface. This interaction is independent of the mode of excitation;
      that is, it does not require evanescent wave or surface-plasmon excitation. In a
      sense, SPCE is the inverse process of the surface plasmon resonance absorption of
      thin metal films. Importantly, SPCE occurs over a narrow angular distribution,
      converting normally isotropic emission into easily collected directional
      emission. Up to 50% of the emission from unoriented samples can be collected,
      much larger than typical fluorescence collection efficiencies near 1% or less.
      SPCE is due only to fluorophores near the metal surface and may be regarded as
      emission from the induced surface plasmons. Autofluorescence from more distal
      parts of the sample is decreased due to decreased coupling. SPCE is highly
      polarized and autofluorescence can be further decreased by collecting only the
      polarized component or only the light propagating with the appropriate angle.
      Examples showing how simple optical configurations can be used in diagnostics,
      sensing, or biotechnology applications are presented. Surface plasmon-coupled
      emission is likely to find widespread applications throughout the biosciences.

PMID- 14690680
TI  - Radiative decay engineering 4. Experimental studies of surface plasmon-coupled
      directional emission.
AB  - Fluorescence is typically isotropic in space and collected with low efficiency.
      In this paper we describe surface plasmon-coupled emission (SPCE), which displays
      unique optical properties and can be collected with an efficiency near 50%. SPCE
      occurs for fluorophores within about 200 nm of a thin metallic film, in our case
      a 50-nm-thick silver film on a glass substrate. We show that fluorophore
      proximity to this film converts the normally isotropic emission into highly
      directional emission through the glass substrate at a well-defined angle from the
      normal axis. Depending on the thickness of the polyvinyl alcohol (PVA) film on
      the silver, the coupling efficiency of sulforhodamine 101 in PVA ranged from 30
      to 49%. Directional SPCE was observed whether the fluorophore was excited
      directly or by the evanescent field due to the surface plasmon resonance. The
      emission is always polarized perpendicular to the plane of incidence,
      irrespective of the polarization of the incident light. The lifetimes are not
      substantially changed, indicating a mechanism somewhat different from that
      observed previously for the effects of silver particles on fluorophores.
      Remarkably, the directional emission shows intrinsic spectral resolution because
      the coupling angles depend on wavelength. The distances over which SPCE occurs,
      10 to 200 nm, are useful because a large number of fluorophores can be localized
      within this volume. The emission of more distant fluorophores does not couple
      into the glass, allowing background suppression from biological samples. SPCE can
      be expected to become rapidly useful in a variety of analytical and medical
      sensing applications.

PMID- 14690681
TI  - A fluorescence-based assay for multisubunit DNA-dependent RNA polymerases.
AB  - The properties of DNA-dependent RNA polymerases have been studied since the
      1960s, but considerable interest in probing RNA polymerase structure/function
      relationships, the roles of different classes of RNA polymerases in cellular
      processes, and the feasibility of using RNA polymerases as drug targets still
      exists. Historically, RNA polymerase activity has been measured by the
      incorporation into RNA of radioisotopically labeled nucleotides. We report the
      development of an assay for RNA polymerase activity that uses the dye RiboGreen
      to detect transcripts by fluorescence and is thus free of the expense, short
      shelf life, and high handling costs of radioisotopes. The method is relatively
      quick and can be performed entirely in microplate format, allowing for the
      processing of dozens to hundreds of samples in parallel. It should thus be well
      suited to use in drug screening and analysis of chromatographic fractions. As
      RiboGreen fluorescence is enhanced by binding to either RNA or DNA, template DNA
      must be removed by DNase digestion and ultrafiltration between the transcription
      and the detection phases of the assay procedure. Although RiboGreen fluorescence
      is sensitive to changes in solvent environment, solvent exchange in the
      ultrafiltration step allows comparison of transcription levels even under
      extremes of salt, pH, etc.

PMID- 14690682
TI  - Detection of protein Z in a renal calculus composed of calcium oxalate
      monohydrate with the use of liquid chromatography-mass spectrometry/mass
      spectrometry following two-dimensional polyacrylamide gel electrophoresis
      separation.
AB  - Protein Z, a vitamin K-dependent plasma protein, has been detected for the first
      time in a renal calculus along with osteopontin and prothrombin. The renal
      calculus was obtained from a hyperuricemic patient. Following two-dimensional
      polyacrylamide gel electrophoresis, the calculus was analyzed with the use of
      liquid chromatography mass spectrometry (LC-MS). The spectrometer was equipped
      with a nanoelectrospray interface and an ion trap. Four peptides were determined
      from a protein in the calculus through LC-MS/MS analysis. Tandem mass spectrum
      database matching tools were used to identify the protein as protein Z. Authentic
      protein Z was also analyzed using the same method, and all four peptides
      determined in the calculus were similarly identified. Whereas protein Z has been
      reported to be one of the vitamin K-dependent calcium-binding proteins, its role
      has not been well established. The fact that protein Z exists in a renal calculus
      composed of calcium oxalate will be beneficial in any future investigations into
      its role in the body.

PMID- 14690683
TI  - Avoidance of nonspecific hybridization by employing oligonucleotide micro-arrays
      generated from hydrolysis polymerase chain reaction probe sequences.
AB  - We have developed a low-density oligonucleotide-based micro-array where 5'-end
      tethered capture probe sequences were derived from Primer Express software. The
      capture probes represent hydrolysis probe sequences devoid of any fluorochromes
      and were shown to retain hybridization binding specificity to their amplicons;
      hybridization specificity was retained independent to probe sequences. This
      procedure allowed the specificity of each capture probe to be verified using real
      time polymerase chain reaction (PCR) in the presence of nucleic acid sequences
      typically expected to be present within a sample and therefore has reduced
      possibility of nonspecific hybridization when used in a micro-array format. We
      propose that specificity-validated probes are applied to form a micro-array for
      the purpose of general target screening, with incumbent multiparallelization and
      cost and time savings. However, if required, the subset of probe sequences of
      interest can be used for quantitative assessment in conventional real-time PCR.

PMID- 14690684
TI  - Characterization of protein kinase A phosphorylation: multi-technique approach to
      phosphate mapping.
AB  - A multi-technique approach to identification and mapping of phosphorylation on
      protein kinase A (PKA) is described. X-ray crystallography revealed
      phosphorylation at T197 and S338 while mass spectrometry (MS) on the intact
      protein suggested phosphorylation at three sites. Tryptic digestion, followed by
      MS, confirmed the presence of three phosphates. However, metal affinity treatment
      of the digest prior to MS revealed the presence of a fourth phosphopeptide.
      Subsequent analysis of the digests using liquid chromatography (LC) coupled with
      quadrupole ion trap (QIT) MS confirmed phosphorylation at S10 and S338 and
      suggested phosphorylation at S139 and T195/197. Unfortunately, identification of
      pS139 was inconclusive due to low signal intensity and early elution in reversed
      phase LC while poor MS/MS data prevented localization of the phosphate to T195 or
      T197. Phosphopeptide modification with ethanethiol, followed by LC QIT-MS/MS,
      identified four phosphopeptides in a single experiment. In addition, the
      fragmentation data provided significantly more sequence information than data
      obtained from unmodified peptides. Data from this study suggested that PKA was
      completely phosphorylated at S10, T197, and S338 and partially phosphorylated at
      S139. These results illustrate that critical information can be lost unless
      multiple MS techniques are used for identification and validation of
      phosphorylation.

PMID- 14690685
TI  - A protein A-based orientation-controlled immobilization strategy for antibodies
      using nanometer-sized gold particles and plasma-polymerized film.
AB  - A novel protein A (PA)-based strategy for the orientation-controlled
      immobilization of antibodies using nanometer-sized gold (Nano-gold) particles and
      an amine-terminated plasma-polymerized film (PPF) has been proposed. A quartz
      crystal microbalance was fabricated, accordingly, coupling with haptoglobin (HP)
      antibody followed by HP immunoassay, as a model test system. The crystal was
      modified with plasma-polymerized n-butyl amine film to deposit Nano-gold
      particles and PA, on which HP antibodies were immobilized. The surface topology
      of the as-prepared crystal was characterized by use of scanning electron
      microscopy. In contrast to the traditional flat gold surface, the assembled Nano
      gold particle monolayer could allow PA molecules bound with higher bioactivity
      and loading amount (density), achieving better antibody-binding capabilities.
      Results indicate that immunosensors prepared using the developed PPF-Nano-gold-PA
      binding procedure exhibit increased analytical performance compared with those
      produced using the direct PA binding procedure and the PPF-based glutaraldehyde
      cross-linking procedure. A HP serum concentration as low as 0.41 nM can be
      determined by this new system. Regenerated simply by rinsing in the acid buffer,
      the proposed sensor can achieve up to 11 assay cycles without significant loss of
      sensitivity.

PMID- 14690686
TI  - Preparation and characterization of Alexa Fluor 594-labeled epidermal growth
      factor for fluorescence resonance energy transfer studies: application to the
      epidermal growth factor receptor.
AB  - We have prepared and characterized a new fluorescent derivative of murine
      epidermal growth factor (EGF), Alexa Fluor 594-labeled EGF (A-EGF), for
      fluorescence studies of EGF-EGF receptor interactions. We describe the synthesis
      of this derivative and its physical and biological characterization. The
      significant overlap between the excitation and the emission spectra of A-EGF
      makes this probe well suited to fluorescence resonance energy homo-transfer.
      Using time-resolved fluorescence to examine the oligomeric state of the EGF
      receptor, we have observed resonance energy homo-transfer of A-EGF bound to EGF
      receptors in cells, but not of A-EGF bound to EGF receptors in membrane vesicles.
      Our results, interpreted in the context of recent crystallographic studies of the
      ligand-binding domains of EGF receptors, suggest that observed fluorescence
      resonance energy transfer does not result from transfer within receptor dimers,
      but rather results from transfer within higher-order oligomers. Furthermore, our
      results support a structural model for oligomerization of EGF receptors in which
      dimers are positioned head-to-head with respect to the ligand-binding site,
      consistent with the head-to-head interactions observed between adjacent receptor
      dimers by X-ray crystallography.

PMID- 14690687
TI  - Detection of protease inhibitors by a reverse zymography method, performed in a
      tris(hydroxymethyl)aminomethane-Tricine buffer system.
AB  - A new detecting method for protease inhibitors, especially for low-molecular
      weight inhibitors, is reported. Inhibitor samples were separated on a protein
      substrate-SDS-polyacrylamide gel in a Tris-Tricine buffer system that improves
      the separation and identification of peptides and low-molecular-weight proteins.
      After electrophoresis, the gel was incubated with the target proteases to
      hydrolyze the background protein substrate. The inhibitor bands, which were
      protected from proteolysis by the target proteases, were stained. Standard low
      molecular-weight inhibitors, such as pepstatin A for pepsin or matrix
      metalloproteases inhibitor I for collagenase, as well as larger inhibitors, such
      as soybean trypsin inhibitor or aprotinin for tryspin and cystatin C for papain,
      were demonstrated by this method and showed clear blue inhibitor bands in the
      white background when the gels were treated with the target proteases. Some
      significant applications of this method are introduced. This method is an ideal
      system for discovering new protease inhibitors in small natural samples.

PMID- 14690688
TI  - SpeedScreen: label-free liquid chromatography-mass spectrometry-based high
      throughput screening for the discovery of orphan protein ligands.
AB  - A high-throughput screening methodology tailored to the discovery of ligands for
      known and orphan proteins is presented. With this method, labeling of neither
      target protein nor screened compounds is required, as the ligands are affinity
      selected by incubation of the protein with mixtures of compounds in aqueous
      binding buffer. Unbound small-molecular-weight compounds are removed from the
      target protein:ligand complex by rapid size-exclusion chromatography in the 96
      well format. The protein fraction is analyzed subsequently by liquid
      chromatography-mass spectrometry for detection and identification of the bound
      ligand. This screening method was validated with known protein:ligand model
      systems and optimized for selection of high-affinity binders in an industrial
      screening environment. All sample handling steps and the analytics are rapid,
      robust, and largely automated, adopting this technology to the needs of present
      high-throughput screening processes. This affinity-selection technology, termed
      SpeedScreen, is currently an integral part of our lead discovery process.

PMID- 14690689
TI  - Estimation of guanine deaminase using guanosine as a "prosubstrate".
AB  - Plasma guanine deaminase (guanase; GD) is well established as an indicator of
      hepatocellular disease, recently being applied in the detection of hepatitis C in
      donor blood and in the diagnosis of hepatoma. No totally efficient, simple method
      for the estimation of plasma GD activity is routine since both guanine and 8
      azaguanine, the substrates of the enzyme, are scarcely soluble in water. This
      difficulty in preparing stable substrates of sufficient concentration has
      resulted in methods that are both troublesome and inaccurate. Here we describe
      the development of new colorimetric and high-performance liquid chromatography
      (HPLC) methods utilizing guanosine as a "prosubstrate." After an initial
      breakdown of the guanosine to guanine using purine nucleoside phosphorylase, the
      ammonia formed as a result of the breakdown of the guanine by GD was estimated
      colorimetrically by the Berthelot reaction. As an alternative or a complementary
      assay, the xanthine also formed was measured using an isocratic HPLC method.
      These methods are suitable for routine assays for measuring plasma GD over a wide
      range of activities.

PMID- 14690690
TI  - Ca2+ transport in mitochondria from yeast expressing recombinant aequorin.
AB  - We have expressed aequorin in mitochondria of the yeast Saccharomyces cerevisiae
      and characterized the resulting strain with respect to mitochondrial Ca(2+)
      transport in vivo and in vitro. When intact cells are suspended in water
      containing 1.4 mM ethanol and 14 mM CaCl(2), the matrix free Ca(2+) concentration
      is 200 nM, similar to the values expected in cytoplasm. Addition of ionophore ETH
      129 allows an active accumulation of Ca(2+) and promptly increases the value to
      1.2 microM. Elevated Ca(2+) concentrations are maintained for periods of 6 min or
      longer under these conditions. Isolated yeast mitochondria oxidizing ethanol also
      accumulate Ca(2+) when ETH 129 is present, but the cation is not retained
      depending on the medium conditions. This finding confirms the presence of a
      Ca(2+) release mechanism that requires free fatty acids as previously described
      [P.C. Bradshaw et al. (2001) J. Biol. Chem. 276, 40502-40509]. When a respiratory
      substrate is not present, Ca(2+) enters and leaves yeast mitochondria slowly, at
      a specific activity near 0.2 nmol/min/mg protein. Transport under these
      conditions equilibrates the internal and external concentrations of Ca(2+) and is
      not affected by ruthenium red, uncouplers, or ionophores that perturb
      transmembrane gradients of charge and pH. This activity displays sigmoid kinetics
      and a K(1/2) value for Ca(2+) that is near to 900 nM, in the absence of ethanol
      or when it is present. It is furthermore shown that the activity coefficient of
      Ca(2+) in yeast mitochondria is a function of the matrix Ca(2+) content and is
      substantially larger than that in mammalian mitochondria. Characteristics of the
      aequorin-expressing strain appear suitable for its use in expression-based
      methods directed at cloning Ca(2+) transporters from mammalian mitochondria and
      for further examining the interrelationships between mitochondrial and
      cytoplasmic Ca(2+) in yeast.

PMID- 14690691
TI  - Hydrogen sulfide consumption measured at low steady state concentrations using a
      sulfidostat.
AB  - Although >10 microM hydrogen sulfide typically is toxic to eukaryotic cells, <1
      microM sulfide is rapidly consumed and oxidized. To measure sulfide consumption
      in such low concentrations, we built a "Sulfidostat." The apparatus uses a
      sulfide-specific electrode to measure the concentration of free sulfide. The
      electrode is connected to a computer that controls a syringe pump. The pump
      injects Na(2)S solution into the sample chamber to maintain a constant
      concentration. Since the response of the electrode to low sulfide concentrations
      at neutral pH had not been previously validated, that was measured. Then using
      the Sulfidostat, the rate of sulfide consumption is the rate at which it is
      pumped into the sample to maintain a constant concentration. The protozoan
      Tetrahymena pyriformis was used to demonstrate the apparatus; maximum sulfide
      consumption occurred near 0.5 microM sulfide at a rate of 250 nmol (g protein)(
      1) s(-1). That is higher than the rate calculated from the disappearance of
      sulfide following a bolus addition, a difference that can be explained by the
      slow response of the electrode and by reversible binding of sulfide by the cells.
      The Sulfidostat can measure sulfide consumption at concentrations lower than
      previously have been possible.

PMID- 14690692
TI  - Simultaneous analysis of docetaxel and the formulation vehicle polysorbate 80 in
      human plasma by liquid chromatography/tandem mass spectrometry.
AB  - An analytical procedure for the simultaneous determination of the anticancer
      agent docetaxel (Taxotere) and its formulation vehicle polysorbate 80 (Tween 80)
      in human plasma samples is described. Sample pretreatment involved a double
      liquid-liquid extraction step with a mixture of acetonitrile/n-butyl chloride
      (1/4, v/v). Separation of the compounds of interest, including the internal
      standard paclitaxel, was achieved on a reversed-phase Waters X-Terra mass
      spectrometry (MS) column (50 x 2.1mm internal diameter) packed with a 3.5-microm
      octadecyl stationary phase, using isocratic elution. Detection of docetaxel and
      polysorbate 80 was performed using tandem MS detection with electrospray
      ionization. Validation results indicated that the method is accurate and precise
      and has lower limits of quantitation of 0.500 nM (approximately 0.4 ng/ml) and
      1.00 microg/ml for docetaxel and polysorbate 80, respectively. The method was
      subsequently used to measure concentrations of docetaxel and polysorbate 80 in
      plasma samples in support of a project to assess the influence of polysorbate 80
      concentrations on the disposition and toxicity profile of docetaxel in cancer
      patients receiving Taxotere.

PMID- 14690693
TI  - Multiple site-directed mutagenesis of more than 10 sites simultaneously and in a
      single round.
AB  - Site-directed mutagenesis is a powerful tool to explore the structure-function
      relationship of proteins, but most traditional methods rely on the mutation of
      only one site at a time and efficiencies drop drastically when more than three
      sites are targeted simultaneously. Many applications in functional proteomics and
      genetic engineering, including codon optimization for heterologous expression,
      generation of cysteine-less proteins, and alanine-scanning mutagenesis, would
      greatly benefit from a multiple-site mutagenesis method with high efficiency.
      Here we describe the development of a simple and rapid method for site-directed
      mutagenesis of more than 10 sites simultaneously with up to 100% efficiency. The
      method uses two terminal tailed primers with a unique 25-nucleotide tail each
      that are simultaneously annealed to template DNA together with the set of
      mutagenic primers in between. Following synthesis of the mutant strand by primer
      extension and ligation with T4 DNA polymerase and ligase, the unique mutant
      strand-specific tails of the terminal primers are used as anchors to specifically
      amplify the mutant strand by high-fidelity polymerase chain reaction. We have
      employed this novel method to mutate simultaneously all 9 and 11 CUG leucine
      codons of the Hyg and Neo resistance genes, respectively, to the Candida albicans
      friendly UUG leucine codon at 100% efficiency.

PMID- 14690694
TI  - 1H NMR spectroscopic evidence of interaction between ibuprofen and lipoproteins
      in human blood plasma.
AB  - Recent studies have suggested that ibuprofen inhibits low-density lipoprotein
      oxidation in a high dose-dependent manner and is a promising drug for treatment
      of the conditions associated with atherosclerosis. In this article, we present
      the NMR spectroscopic evidence for the interaction between ibuprofen and
      phospholipids in lipoprotein particles in intact human plasma. Ibuprofen caused
      chemical shift upfield drifts for the protons of -N(+)(CH(3))(3) moieties of
      phosphatidylcholine and sphingomyelin, olefinic chains (-CH[double bond]CH[bond],
      [bond]CH[triple bond]CHCH(2)CH[triple bond]CH[bond],
      [bond](CH(2))(n)CH(2)CH[double bond]), and (CH(2))(n) and CH(3) groups, from
      unsaturated lipids in lipoprotein particles. The ibuprofen may interact directly
      with the above-mentioned groups of phospholipids or induce structural changes in
      the lipoproteins. This may shed light on the mechanism by which the drug protects
      against oxidative modification of lipoproteins.

PMID- 14690695
TI  - A high-throughput resonance energy transfer assay for Staphylococcus aureus DNA
      ligase.

PMID- 14690696
TI  - A one-tube, two-step polymerase chain reaction-based site-directed mutagenesis
      method with simple identification of the mutated product.

PMID- 14690697
TI  - Determination of granulocyte colony stimulating factor and its antibody in human
      serum samples using the BIAcore 3000 biosensor.

PMID- 14690698
TI  - An enzymatic bioluminescent assay of DNA ligation.

PMID- 14690699
TI  - Dynamic allele-specific oligonucleotide hybridization on solid support.

PMID- 14690700
TI  - Whole-genome amplification of DNA from residual cells left by incidental contact.

PMID- 14690703
TI  - Self-organising continuous attractor networks with multiple activity packets, and
      the representation of space.
AB  - 'Continuous attractor' neural networks can maintain a localised packet of
      neuronal activity representing the current state of an agent in a continuous
      space without external sensory input. In applications such as the representation
      of head direction or location in the environment, only one packet of activity is
      needed. For some spatial computations a number of different locations, each with
      its own features, must be held in memory. We extend previous approaches to
      continuous attractor networks (in which one packet of activity is maintained
      active) by showing that a single continuous attractor network can maintain
      multiple packets of activity simultaneously, if each packet is in a different
      state space or map. We also show how such a network could by learning self
      organise to enable the packets in each space to be moved continuously in that
      space by idiothetic (motion) inputs. We show how such multi-packet continuous
      attractor networks could be used to maintain different types of feature (such as
      form vs colour) simultaneously active in the correct location in a spatial
      representation. We also show how high-order synapses can improve the performance
      of these networks, and how the location of a packet could be read by motor
      networks. The multiple packet continuous attractor networks described here may be
      used for spatial representations in brain areas such as the parietal cortex and
      hippocampus.

PMID- 14690704
TI  - Combining Hebbian and reinforcement learning in a minibrain model.
AB  - A toy model of a neural network in which both Hebbian learning and reinforcement
      learning occur is studied. The problem of 'path interference', which makes that
      the neural net quickly forgets previously learned input-output relations is
      tackled by adding a Hebbian term (proportional to the learning rate nu) to the
      reinforcement term (proportional to delta) in the learning rule. It is shown that
      the number of learning steps is reduced considerably if 1/4<nu/delta<1/2, i.e. if
      the Hebbian term is neither too small nor too large compared to the reinforcement
      term.

PMID- 14690705
TI  - Neocognitron capable of incremental learning.
AB  - This paper proposes a new neocognitron that accepts incremental learning, without
      giving a severe damage to old memories or reducing learning speed. The new
      neocognitron uses a competitive learning, and the learning of all stages of the
      hierarchical network progresses simultaneously. To increase the learning speed,
      conventional neocognitrons of recent versions sacrificed the ability of
      incremental learning, and used a technique of sequential construction of layers,
      by which the learning of a layer started after the learning of the preceding
      layers had completely finished. If the learning speed is simply set high for the
      conventional neocognitron, simultaneous construction of layers produces many
      garbage cells, which become always silent after having finished the learning. The
      proposed neocognitron with a new learning method can prevent the generation of
      such garbage cells even with a high learning speed, allowing incremental
      learning.

PMID- 14690706
TI  - Global asymptotic stability of Hopfield neural network involving distributed
      delays.
AB  - In the paper, we study dynamical behaviors of Hopfield neural networks system
      with distributed delays. Some new criteria ensuring the existence and uniqueness,
      and the global asymptotic stability (GAS) of equilibrium point are derived. In
      the results, we do not assume that the signal propagation functions satisfy the
      Lipschitz condition and do not require them to be bounded, differentiable or
      strictly increasing. Moreover, the symmetry of the connection matrix is not also
      necessary. Thus, we improve some previous works of other researchers. These
      conditions are presented in terms of system parameters and have importance
      leading significance in designs and applications of the GAS for Hopfield neural
      networks system with distributed delays. Two examples are also worked out to
      demonstrate the advantages of our results.

PMID- 14690707
TI  - Associative memory by recurrent neural networks with delay elements.
AB  - The synapses of real neural systems seem to have delays. Therefore, it is
      worthwhile to analyze associative memory models with delayed synapses. Thus, a
      sequential associative memory model with delayed synapses is discussed, where a
      discrete synchronous updating rule and a correlation learning rule are employed.
      Its dynamic properties are analyzed by the statistical neurodynamics. In this
      paper, we first re-derive the Yanai-Kim theory, which involves macrodynamical
      equations for the dynamics of the network with serial delay elements. Since their
      theory needs a computational complexity of O(L4t) to obtain the macroscopic state
      at time step t where L is the length of delay, it is intractable to discuss the
      macroscopic properties for a large L limit. Thus, we derive steady state
      equations using the discrete Fourier transformation, where the computational
      complexity does not formally depend on L. We show that the storage capacity
      alphaC is in proportion to the delay length L with a large L limit, and the
      proportion constant is 0.195, i.e. alphaC=0.195L. These results are supported by
      computer simulations.

PMID- 14690708
TI  - Steepest descent with momentum for quadratic functions is a version of the
      conjugate gradient method.
AB  - It is pointed out that the so called momentum method, much used in the neural
      network literature as an acceleration of the backpropagation method, is a
      stationary version of the conjugate gradient method. Connections with the
      continuous optimization method known as heavy ball with friction are also made.
      In both cases, adaptive (dynamic) choices of the so called learning rate and
      momentum parameters are obtained using a control Liapunov function analysis of
      the system.

PMID- 14690709
TI  - A comparative study of two modeling approaches in neural networks.
AB  - The neuron state modeling and the local field modeling provides two fundamental
      modeling approaches to neural network research, based on which a neural network
      system can be called either as a static neural network model or as a local field
      neural network model. These two models are theoretically compared in terms of
      their trajectory transformation property, equilibrium correspondence property,
      nontrivial attractive manifold property, global convergence as well as stability
      in many different senses. The comparison reveals an important stability
      invariance property of the two models in the sense that the stability (in any
      sense) of the static model is equivalent to that of a subsystem deduced from the
      local field model when restricted to a specific manifold. Such stability
      invariance property lays a sound theoretical foundation of validity of a useful,
      cross-fertilization type stability analysis methodology for various neural
      network models.

PMID- 14690710
TI  - Dynamics of periodic delayed neural networks.
AB  - This paper formulates and studies a model of periodic delayed neural networks.
      This model can well describe many practical architectures of delayed neural
      networks, which is generalization of some additive delayed neural networks such
      as delayed Hopfield neural networks and delayed cellular neural networks, under a
      time-varying environment, particularly when the network parameters and input
      stimuli are varied periodically with time. Without assuming the smoothness,
      monotonicity and boundedness of the activation functions, the two functional
      issues on neuronal dynamics of this periodic networks, i.e. the existence and
      global exponential stability of its periodic solutions, are investigated. Some
      explicit and conclusive results are established, which are natural extension and
      generalization of the corresponding results existing in the literature.
      Furthermore, some examples and simulations are presented to illustrate the
      practical nature of the new results.

PMID- 14690711
TI  - Mixed states on neural network with structural learning.
AB  - We investigated the properties of mixed states in a sparsely encoded associative
      memory model with a structural learning method. When mixed states are made of s
      memory patterns, s types of mixed states, which become equilibrium states of the
      model, can be generated. To investigate the properties of s types of the mixed
      states, we analyzed them using the statistical mechanical method. We found that
      the storage capacity of the memory pattern and the storage capacity of only a
      particular mixed state diverge at the sparse limit. We also found that the
      threshold value needed to recall the memory pattern is nearly equal to the
      threshold value needed to recall the particular mixed state. This means that the
      memory pattern and the particular mixed state can be made to easily coexist at
      the sparse limit. The properties of the model obtained by the analysis are also
      useful for constructing a transform-invariant recognition model.

PMID- 14690712
TI  - Practical selection of SVM parameters and noise estimation for SVM regression.
AB  - We investigate practical selection of hyper-parameters for support vector
      machines (SVM) regression (that is, epsilon-insensitive zone and regularization
      parameter C). The proposed methodology advocates analytic parameter selection
      directly from the training data, rather than re-sampling approaches commonly used
      in SVM applications. In particular, we describe a new analytical prescription for
      setting the value of insensitive zone epsilon, as a function of training sample
      size. Good generalization performance of the proposed parameter selection is
      demonstrated empirically using several low- and high-dimensional regression
      problems. Further, we point out the importance of Vapnik's epsilon-insensitive
      loss for regression problems with finite samples. To this end, we compare
      generalization performance of SVM regression (using proposed selection of epsilon
      values) with regression using 'least-modulus' loss (epsilon=0) and standard
      squared loss. These comparisons indicate superior generalization performance of
      SVM regression under sparse sample settings, for various types of additive noise.

PMID- 14690713
TI  - Experimentally optimal nu in support vector regression for different noise models
      and parameter settings.
AB  - In Support Vector (SV) regression, a parameter nu controls the number of Support
      Vectors and the number of points that come to lie outside of the so-called
      epsilon-insensitive tube. For various noise models and SV parameter settings, we
      experimentally determine the values of nu that lead to the lowest generalization
      error. We find good agreement with the values that had previously been predicted
      by a theoretical argument based on the asymptotic efficiency of a simplified
      model of SV regression. As a side effect of the experiments, valuable information
      about the generalization behavior of the remaining SVM parameters and their
      dependencies is gained. The experimental findings are valid even for complex
      'real-world' data sets. Based on our results on the role of the nu-SVM
      parameters, we discuss various model selection methods.

PMID- 14690714
TI  - Discrimination networks for maximum selection.
AB  - We construct a novel discrimination network using differentiating units for
      maximum selection. In contrast to traditional competitive architectures like
      MAXNET the discrimination network does not only signal the winning unit, but also
      provides information about its evidence. In particular, we show that a
      discrimination network converges to a stable state within finite time and derive
      three characteristics: intensity normalization (P1), contrast enhancement (P2),
      and evidential response (P3). In order to improve the accuracy of the evidential
      response we incorporate distributed redundancy into the network. This leads to a
      system which is not only robust against failure of single units and noisy data,
      but also enables us to sharpen the focus on the problem given in terms of a more
      accurate evidential response. The proposed discrimination network can be regarded
      as a connectionist model for competitive learning by evidence.

PMID- 14690717
TI  - Soft-tissue abscess involving Actinomyces odontolyticus and two Prevotella
      species in an intravenous drug abuser.
AB  - Skin and soft-tissue infections in intravenous users comprise a variety of
      microorganisms and anaerobic bacteria are frequently involved in these
      suppurative infections. A case of subcutaneous abscess into anterior femoral
      muscles involving Actinomyces odontolyticus and two Prevotella species
      (Prevotella buccae and Prevotella melaninogenica) in an intravenous drug abuser
      is presented. This combination of microorganisms has not previously been
      described in soft-tissue infections. The patient volunteering that he licked his
      hypodermic needle prior to cocaine injection supports that the implicating
      bacteria originated from the oral cavity. Eventually, the patient recovered and
      at a 6-month follow-up a gradual improvement of his subcutaneous infection was
      noticed.

PMID- 14690718
TI  - Analysis of protein expression by mammalian cell lines stably expressing lactate
      dehydrogenase-elevating virus ORF 5 and ORF 6 proteins.
AB  - Lactate dehydrogenase-elevating virus (LDV) has a strict species-specificity.
      Because only a subset of mouse primary macrophages have been identified that can
      support LDV replication in vitro, the precise molecular mechanism of viral entry
      and replication remains unclear. To analyze the LDV envelope proteins, which
      probably mediate viral attachment to the host cell, we developed a mammalian
      system for stable co-expression of LDV open reading frame (ORF) 5- and ORF 6
      encoded proteins (ORF 5 and ORF 6 proteins), which correspond to envelope VP-3
      and M/VP-2, respectively, and compared these expressed proteins to the native
      ones. Western blotting analysis combined with N-glycanase digestion revealed that
      ORF 5 and ORF 6 proteins were similar in size to native VP-3 and M/VP-2, and that
      ORF 5 protein was N-glycosylated, like the native VP-3. Immunofluorescence
      microscopy revealed that both ORF 5 and ORF 6 proteins were distributed
      throughout the cytoplasm and were colocalized in most cells. Moreover, ORF 5
      protein was localized both in the perinuclear region and the Golgi complex and
      transported to the cell surface. This mammalian expression system in which the
      exogenously expressed proteins closely resemble the native proteins will provide
      the experimental basis for further studies of the interactions between LDV
      envelope proteins and host cells.

PMID- 14690719
TI  - Induction of T cell anergy by the treatment with IL-10-treated dendritic cells.
AB  - In order to apply for reducing graft versus host disease in allogeneic stem cell
      transplantation, the study concerning the induction of specific T cell anergy was
      designed. Normal allogeneic lymphocytes, which were co-cultured with IL-10
      treated immature dendritic cells in the first mixed leukocyte culture (MLC), were
      cultured with mature dendritic cells of the same origin as IL-10-treated immature
      dendritic cells in the second MLC. By co-culturing with IL-10-treated immature
      dendritic cells, the response of normal lymphocytes to mature dendritic cells
      cultured from the same individual as that of IL-10-treated dendritic cells was
      markedly reduced, compared with the lymphocytes cultured with non-treated
      dendritic cells or IL-10-treated dendritic cells from a third party individual.
      The present study demonstrated that antigen specific T cell anergy was generated
      by priming allogeneic lymphocytes with IL-10-treated immature dendritic cells.
      These data suggested the applicability of IL-10-treated recipient dendritic cells
      for the induction of recipient cell-specific donor T cell anergy in donor graft.

PMID- 14690720
TI  - Production and evaluation of alloantibodies against sheep MHC Class I antigens.
AB  - In this work more than 600 sera obtained from three different sources (parous
      ewes and directed immunizations with whole blood or leucocytes) were tested for
      cytotoxic antilymphocyte antibodies. A high incidence of cytotoxic antibodies in
      pregnancy-stimulated animals was confirmed. For the sake of comparison, a
      comprehensive review of other studies in sheep and other species was performed.
      There are several different reasons that could explain the differences found
      between these studies, among them the time of sampling and the cytotoxic assay
      procedures. Moreover, antibodies were also found in non-pregnant females which
      may imply that pregnancy is not the only stimulus for antibody production and
      environmental factors, such as molecular mimicry between infectious agents and
      lymphocyte antigens, could be the reason for their appearance. In the case of
      alloimmunizations with leucocytes or whole blood the results were very close to
      those obtained in goats. Taking into account the Strength Index, the immunization
      sera were of higher quality. Our results support the methodology of Nesse and
      Larsen since one injection of whole blood of the lamb is an easy procedure that
      produces alloantisera with a high value for major histocompatibility complex
      Class I antigens typing.

PMID- 14690721
TI  - Polymerase chain reaction with a primer pair in the 16S-23S rRNA spacer region
      for detection of Mycoplasma pulmonis in clinical isolates.
AB  - To develop a diagnostic tool to identify Mycoplasma pulmonis (M. pulmonis) in
      clinical isolates, we developed a polymerase chain reaction (PCR) assay using
      primers specific for the 16S-23S rRNA intergenic spacer region (SR) of M.
      pulmonis. One pair of PCR primers reacted specifically with two reference strains
      of M. pulmonis tested and seven samples isolated from naturally infected rats.
      The primer pair did not produce PCR products of the correct size from any other
      rodent or human mycoplasmas or cellular DNA from rodent lungs. Specificity of the
      PCR assay was confirmed by Southern blotting with probe specific for the SR of M.
      pulmonis. The PCR assay for detection of M. pulmonis established in this study is
      suitable for diagnosis of M. pulmonis infection in clinical cases.

PMID- 14690722
TI  - Serotypes and anti-microbial susceptibility of Plesiomonas shigelloides isolates
      from humans, animals and aquatic environments in different countries.
AB  - A total of 73 strains of Plesiomonas shigelloides isolated from humans (24
      strains) animals (21 strains) and aquatic environment (28 strains) were
      determined for their O:H serotype and susceptibility to 18 anti-microbial
      substances and to the vibriostatic agent O/129. Of all strains, 86.3% were
      typeable by the O and 94.5% by the H anti-sera used. The serotype distribution
      was heterogeneous within a country and between the countries. Of the 57 different
      serotypes identified, O11:H2 (2 strains), O22:H3 (4 strains), O35:HH11 (2
      strains), O52:H3 (2 strains) and O90:H6 (2 strains) were found among isolates
      from humans and animals (mainly in cats) in Finland and Cuba, and O23:H1a1b (3
      strains) among isolates from environmental sources in Slovak Republic and Italy.
      Most (93-100%) of all strains were susceptible to all anti-microbials tested but
      resistant (92-96%) to the broad-spectrum penicillins (ampicillin, mezlocillin).
      No correlation between anti-microbial resistance patterns and serotypes was
      found.

PMID- 14690723
TI  - Isolation of pathogenic Listeria monocytogenes and detection of antibodies
      against phosphatidylinositol-specific phospholipase C in buffaloes.
AB  - The isolation of pathogenic Listeria spp. in bacteriological samples, and anti
      phosphatidylinositol-specific phospholipase C (anti-PIPLC) antibodies in sera of
      buffaloes were studied. Isolation of the pathogen was attempted from the samples
      by selective enrichment in University of Vermont Medium and plating onto
      Dominguez-Rodriguez isolation agar. Pathogenicity of the isolates was tested by
      Christie, Atkins, Munch Petersen test and mice incoulation test. Listeria spp.
      and L. monocytogenes were isolated from 8.8 and 2.4%, and 4.8 and 1.6% of 125
      each meat and blood samples, respectively. Out of the 125 samples each of feacal,
      nasal and vaginal swabs from buffaloes 8 and 4%, 13.6 and 2.4%, and 6.4 and 2.4%
      were positive for Listeria spp. and L. monocytogenes, respectively. L. ivanovii
      was confirmed from 0.8% vaginal sample. A total of 125 serum samples were tested
      by phosphatidylinositol-specific phospholipase C (PIPLC) based indirect ELISA of
      which 4.0% turned out to be seropositive.

PMID- 14690725
TI  - Visions and revisions--a society visiting its roots.

PMID- 14690726
TI  - Aortic valve repair for aortic insufficiency in adults: a contemporary review and
      comparison with replacement techniques.
AB  - In evaluating the goal of aortic valve preservation, there have been 11 reports
      of large series of aortic valve repair for aortic insufficiency in adults
      published in recent years. We sought to analyze the validity of these methods and
      compare them to published results for bioprosthetic valves, pulmonary autografts,
      and aortic homografts. From 1990 to 2002, 761 adult aortic valve repairs were
      reported. Perioperative morbidity ranged from 3.6 to 23% (mean 14%), early
      mortality 0-8% (mean 3.6%), and late mortality 0-8% (mean 2.8%). The 5- and 10
      year freedom from reoperation rates for repair were 89 and 64%. Although early
      results are good, long-term analysis suggests that, as a group, the durability of
      repair is unclear. Patients with rheumatic valvular disease appear to have an
      increased incidence of recurrence and repair failure. Although suture line
      dehiscence continues to be both an early and late complication with repair, the
      long-term morbidity and mortality is low and valve repair may be an option in
      carefully selected patients. However, the inability to break down the results by
      techniques does not allow for a definitive conclusion. Further subanalysis is
      necessary as larger series are reported. Proponents must attempt to separate
      successful from unsuccessful techniques. Aortic valve repair is a technique in
      evolution.

PMID- 14690727
TI  - Prevention of atrial fibrillation after cardiac valvular surgery by epicardial,
      biatrial synchronous pacing.
AB  - OBJECTIVE: Postoperative atrial fibrillation (AF) after cardiac surgery is a
      frequent complication after valvular surgery (30-60%). The purpose of this
      prospective, randomized study was to determine if biatrial synchronous pacing
      reduces postoperative AF after cardiac valvular surgery as compared to
      conventional therapy. METHODS: Eighty patients subjected to valvular surgery (52
      men, age 66 +/- 10 years) were randomized to one of two groups: one group was
      treated with biatrial, synchronous pacing (BAP) for 72 h postoperatively (n=40)
      the other group received no atrial pacing (controls; n=40). All patients had one
      pair of epicardial wires attached to the right atrium. An additional electrode
      was placed to the left atrium in the BAP group. These patients were continuously
      paced at a rate of 10 beats per minute higher than the intrinsic rate starting
      immediately after surgery. All patients were monitored with full disclosure
      telemetry or Holter monitors to identify onset of AF. RESULTS: Eighteen of the 40
      patients in the control group (45%) developed AF within the first 3 days
      postoperatively as compared to eight patients (20%) in the BAP group (P=0.02). No
      complications occurred associated with the placement, maintenance and removal of
      the atrial pacing electrodes. CONCLUSIONS: Temporary, biatrial synchronous pacing
      during the first 3 postoperative days is safe and has a significant rhythm
      stabilizing effect in patients undergoing valvular cardiac surgery.

PMID- 14690728
TI  - Surgical angioplasty of the left main coronary artery and/or proximal segment of
      the right coronary artery by pulmonary autograft patch.
AB  - OBJECTIVES: There are controversial opinions about the expediency of performance
      of the surgical angioplasty of the left main coronary artery (LMCA) and/or
      proximal segment of the right coronary artery (RCA) in rare cases of isolated
      lesion or with limited involving of distal coronary branches. One of the many
      fears restraining a wider performance of this operation is the uncertainty in
      longevity of patch material. It is supposed that the autovein has tendency to
      proliferating degeneration similar to that in case of coronary artery bypass
      grafting (CABG), while the autopericardium may be subjected to calcification.
      Autoarterial patches have a limited width. To withdraw these real or hypothetical
      negative properties of patch materials we offer to harvest the pulmonary
      autograft patch (PAP) for coronary angioplasty. METHODS: Our experience with PAP
      angioplasty of LMCA and/or proximal segment of RCA includes four cases.
      Simultaneous angioplasty of LMCA and proximal segment of RCA was performed in one
      patient; angioplasty of LMCA--in two patients; angioplasty of RCA--in one
      patient. In two cases the stenosis of LMCA was accompanied by stenotic lesion of
      left anterior descending coronary artery (LAD). The surgical approach to LMCA was
      performed by complete crossing of pulmonary artery (PA). There was no necessity
      to use any plastic material for restoring of PA integrity in all cases. RESULTS:
      All patients survived after the operation. The postoperative course was
      uncomplicated except one case of LMCA/LAD lesion. There was a temporary low
      cardiac output syndrome and ventricular arrhythmia resulting in additional CABG
      as 'back-up' procedure. This complication was not a consequence of impassability
      of LMCA because its good patency was established at control coronary angiograms.
      The postoperative coronary angiograms were performed in all cases. They showed a
      satisfactory width of the main coronary vessels. The maximal follow-up period is
      30 months. CONCLUSION: We suppose that the use of viable pulmonary autograft
      patch for surgical angioplasty of LMCA and proximal segment of RCA removes one of
      a lot of fears, which restrain the wider use of this alternative to CABG
      operation.

PMID- 14690729
TI  - Analysis of thoracic aortic blood flow during off-pump coronary artery bypass
      surgery.
AB  - OBJECTIVES: The non-invasive monitoring of thoracic aortic blood flow (TABF)
      during off-pump coronary artery bypass (OPCAB) surgery is becoming more commonly
      used and proved to be invaluable in the early detection of haemodynamic
      compromise due to heart displacement. The aim of this study was to analyze the
      changes in the TABF during OPCAB using transoesophageal Doppler and compare them
      with the changes observed by other monitoring methods as cardiac output, invasive
      pulmonary and radial pressures and mixed venous oxygen saturation. METHODS: The
      measurements obtained from classic haemodynamic monitoring methods including the
      radial artery line and the pulmonary artery catheter with continuous monitoring
      of the cardiac output and mixed venous blood oxygen saturation were compared to
      the measurements of TABF obtained from a transoesophageal Doppler probe in 15
      consecutive patients who underwent OPCAB surgery. RESULTS: The TABF decreased
      significantly during the construction of coronary anastomoses from 3.42 +/- 0.94
      l/min (baseline) to 2.2 +/- 0.8 l/min during the first coronary anastomosis and
      then to 2.14 +/- 1.12 l/min during the second coronary anastomosis (F=4.29,
      P=0.008). TABF returned to the baseline values (2.85 +/- 1.19 l/min) at chest
      closure. The cardiac output measurement showed no significant decrease compared
      to baseline. CONCLUSIONS: Low TABF occurred without significant changes in the
      measurements obtained from classic haemodynamic monitoring methods during OPCAB
      surgery. This finding could be of vital importance in helping improve the
      monitoring and consequently the management of patients undergoing OPCAB surgery.

PMID- 14690730
TI  - Activation of complement and leukocyte receptors during on- and off pump coronary
      artery bypass surgery.
AB  - OBJECTIVE: The aim of this prospective, randomised study was to investigate the
      influence of extracorporeal circulation on the inflammatory response, our
      hypothesis being that off pump coronary artery bypass grafting (OFFCAB)
      procedures would generate less activation than on pump procedures (ONCAB).
      METHODS: Patients admitted for elective CABG were randomised to either ONCAB or
      OFFCAB surgery and blood samples were taken during and up to 24 h after the
      operation. We measured complement factors C5a and the terminal complement complex
      (TCC, C59-b), and the interleukins IL-6 and IL-8. Leukocytes were studied for
      cellular counts and adhesion molecules (CD11b, CD35 and CD62L) by flow cytometry.
      We included a combination of activity markers with different aspects of
      neutrophil function and combined these with in vitro activation. RESULTS: The
      complement factors C5a and TCC showed a more rapid (P=0.02, P<0.001) and TCC a
      more profound (P<0.001) increase in the ONCAB group than in the OFFCAB group
      during the operation, after that there were no inter-group differences. Cellular
      markers, cell counts and interleukin levels were activated by surgery but with no
      difference between groups. CONCLUSION: This prospective, randomised study showed
      less complement activation in low risk OFFCAB, compared to ONCAB patients.

PMID- 14690731
TI  - Description and evaluation of a ventriculo-coronary artery bypass device that
      provides bi-directional coronary flow.
AB  - OBJECTIVE: The objective of this study was to assess acute patency of a new
      myocardial revascularization device that connects the left ventricular cavity to
      a coronary artery (termed ventriculo-coronary artery bypass, VCAB) thereby
      providing proximal and distal blood flow from the site of the anastomosis.
      METHODS: A device made of expanded polytetrafluoroethylene and low density
      polyethylene was implanted from the base of the left ventricle to the mid left
      anterior descending coronary artery (LAD) in 11 juvenile domestic pigs using a
      beating heart approach. Flow rates were measured in the distal LAD before and
      after implant using ultrasonic flow techniques, and patency was assessed at
      explant at either 2 or 4 weeks post-implantation. Myocardial perfusion using
      positron emission tomography (PET) was assessed in a separate set of pigs (n=2)
      revascularized by VCAB 2 weeks post-implant. RESULTS: Net forward flow distal to
      the implanted device was 73 +/- 15% of native LAD flow. PET demonstrated that the
      target myocardium was perfused at 85% of that seen in the remote, control
      myocardium. Device patency rate was 80% (4/5) at 2 weeks in one set of pigs and
      83% (5/6) at 4 weeks in a second set of pigs. Histologic analysis showed
      formation of neointima along the extraventricular segment of the device.
      CONCLUSIONS: This study demonstrates the promise of perfusing ischemic myocardium
      using a VCAB approach with a device that provides blood flow both proximal and
      distal to the anastomosis. Patency of the transmyocardial device was encouraging
      at 2 and 4 weeks and warrants further investigation.

PMID- 14690732
TI  - European system for cardiac operative risk evaluation predicts long-term survival
      in patients with coronary artery bypass grafting.
AB  - OBJECTIVE: To evaluate the accuracy of predicting long-term mortality in patients
      with coronary artery bypass grafting (CABG) by using the European system for
      cardiac operative risk evaluation (EuroSCORE). METHODS: Medical records of
      patients with CABG (n=3760) between January 1992 and March 2002 were
      retrospectively reviewed and their predicted surgical risk was calculated
      according to the standard (study A) and logistic (study B) EuroSCORE. In study A
      the patients were divided into six groups: 0-2 (n=610), 3-5 (n=1479), 6-8
      (n=1099), 9-11 (n=452), 12-14 (n=103) and >14 (n=17). In study B the patients
      were divided into seven groups: 0.00-2.00 (n=447), 2.01-5.00 (n=1190), 5.01-10.00
      (n=890), 10.01-20.00 (n=686), 20.01-30.00 (n=234), 30.01-60.00 (n=254) and >60.00
      (n=59). Long-term survival was obtained by the National Death Index and Kaplan
      Meier curves were constructed and compared employing the log-rank test.
      Multivariate Cox regression analysis was performed in order to control for pre,
      intra and postoperative factors and adjusted hazard ratios were calculated for
      standard and logistic EuroSCORE groups. The receiver operating characteristic
      (ROC) curves were plotted to assess the discrimination ability of the EuroSCORE.
      RESULTS: In study A there were differences among the six groups in 30-day
      mortality (0.7%, 1.0%, 3.1%, 4.6%, 13.6% and 23.5%; P<0.001), in major
      complications (8.5%, 10.4%, 16.2%, 20.4%, 31.1% and 35.3%; P<0.001) as well as in
      actuarial long-term survival (86.2%, 79.6%, 53.6%, 37.9%, 24.9% and 0% from
      EuroSCORE 0-2 to >14; P<0.001). In study B there were differences among the seven
      groups in 30-day mortality (0.9%, 1.1%, 1.2%, 3.6%, 3.4%, 8.7% and 15.3%;
      P<0.001), major complications (8.5%, 10.1%, 12.1%, 18.4%, 16.2%, 26.0% and 30.5%;
      P<0.001) as well as in actuarial long-term survival (89.5%, 79.9%, 66.9%, 51.0%,
      40.3%, 38.4% and 13.7% from EuroSCORE 0.00-2.00 to >60.00; P<0.001). Multivariate
      Cox regression analysis confirmed that EuroSCORE (standard or logistic) was a
      statistically significant predictor for long-term mortality, while the area under
      the ROC curve was 0.72 for either standard or logistic EuroSCORE. CONCLUSION: The
      predicted surgical risk in CABG patients as calculated by standard or logistic
      EuroSCORE is a strong predictor for long-term survival in addition to predicting
      operative survival for which it was originally designed.

PMID- 14690733
TI  - Long-term cardiac survival after reoperative coronary artery bypass grafting.
AB  - OBJECTIVE: Despite advances in cardiac surgery, the risk of reoperative coronary
      artery bypass surgery (RECABG) still exceeds those of a primary myocardial
      revascularization and also the late results are not so favourable. In this study,
      long-term cardiac survival is analyzed. METHODS: We analyzed long-term cardiac
      survival of 466 patients who survived the first 6 months after a RECABG between
      January 1987 and December 1998. Actuarial survival estimates were calculated and
      pre- and peroperative variables were analyzed to identify predictors of long-term
      cardiac related mortality. RESULTS: Mean follow-up was 7.7 +/- 3.8 years (1-17
      years), and follow-up was 95.6% complete. One-year cardiac survival was 98.2%, 5
      year: 91.0%, 10-year: 78.7% and 14-year survival 60.2%. Cardiac survival was only
      significantly superior for patients under 65 years of age at the moment of the
      RECABG. Impaired left ventricular function was identified as the only independent
      predictor of late cardiac-related mortality. CONCLUSION: The long-term survival
      in patients undergoing RECABG is acceptable. Once patients survived the first 6
      postoperative months, advanced age (>65 years) is affecting long-term cardiac
      survival and impaired left ventricular function is the only independent predictor
      of late cardiac mortality.

PMID- 14690734
TI  - High prevalence of unsuspected abdominal aortic aneurysms in patients
      hospitalised for surgical coronary revascularisation.
AB  - OBJECTIVES: Prevalence of abdominal aortic aneurysms (AAA) is not exactly known
      among patients with coronary artery disease (CAD) who are considered for surgical
      revascularisation. We evaluated the value of screening AAA among coronary
      patients admitted in our cardiovascular surgery unit. METHODS: Over a 24-month
      period, an abdominal echography was proposed to male patients aged 60 or more
      while hospitalised for surgical coronary revascularisation. Patients with
      previous investigation of the aorta were excluded. The aorta was considered
      aneurysmal when the anterior-posterior diameter was of 30 mm or more. RESULTS:
      Three hundred and ninety-five consecutive patients all accepted a proposed
      abdominal echographic screening for AAA. Forty unsuspected AAA were detected
      (10.1%). The mean diameter was 38.9 +/- 1.3 mm. Four AAA were larger than 50 mm
      and considered for surgery after the CABG procedure. Surveillance was proposed to
      the other 36, especially the 10 patients with an AAA larger than 40 mm. Patients
      with AAA were significantly older than those without AAA (71.3 +/- 0.8 vs. 69.4
      +/- 0.3 years, P<0.05). Smoking history (P<0.05) and hypertension (P<0.05) were
      also associated more frequently with AAA. More than 16% of the patients being
      smokers and suffering hypertension presented with unsuspected AAA. CONCLUSIONS:
      In-hospital screening of AAA is very efficient among patients with coronary
      artery disease. Therefore, patients with CAD may be considered for routine AAA
      screening.

PMID- 14690735
TI  - Metabolic changes induced by ischemia and cardioplegia: a study employing cardiac
      microdialysis in pigs.
AB  - OBJECTIVE: The present study investigates dynamic changes of myocardial
      metabolism in response to ischemia, cardioplegia, and extracorporeal circulation
      (ECC) in order to differentiate between the contributing effects of each of these
      interventions. Furthermore, warm blood cardioplegia versus empty beating of the
      heart were compared as methods to resuscitate the ischemic myocardial metabolism.
      METHODS: Swedish Landrace pigs on ECC (ECC) were compared with pigs on ECC with
      warm ischemic cardiac arrest (ischemia) or on ECC with warm ischemic arrest
      followed by warm blood cardioplegia (ischemia-cardioplegia), using sham-operated
      pigs as controls (n=7 in each group). Microdialysis probes were placed on the
      surface of the left ventricle and in the femoral artery for serial evaluation of
      metabolites in the intracardiac extracellular fluid and arterial blood. When
      hearts started in ventricular fibrillation (VF), it was electroconverted after 10
      min of normal blood reperfusion. If VF started after 10 min of reperfusion
      electroconversion was immediately performed. RESULTS: There were no differences
      between groups in arterial contents of serine, citrulline, arginine, inosine,
      hypoxanthine, guanosine, aspartate, glutamate, pyruvate, or asparagine throughout
      the observation period. Systemic lactate increased in pigs subjected to ischemia
      (P<0.001) or ischemia and cardioplegia (P=0.002), highest in the ischemia only
      group (P=0.002). In left ventricular microdialysates, lactate increased in pigs
      subjected to ischemia alone (P<0.001 vs. ECC) and ischemia and cardioplegia
      (P=0.004 vs. ECC). Guanosine increased in ischemia versus ECC (P=0.002), while
      hypoxanthine was increased in microdialysates of both ischemic (P=0.002) and
      ischemic-cardioplegic (P=0.001) pig hearts. Inosine was increased in pigs
      subjected to ischemia and cardioplegia (P<0.001 vs. ECC). All ischemic hearts
      started with VF, but while in the warm ischemia group VF started within 10 min of
      reperfusion, the ischemia-cardioplegia group had a longer asystolia with VF
      starting 11-22 min of blood reperfusion. CONCLUSION: The heart should be allowed
      to start empty beating rather than by the use of warm continuous blood
      cardioplegia. Microdialysis and sampling of interstitial metabolites may be
      advantageous when an increased sensitivity is needed or when repeated blood
      sampling is difficult or contraindicated in monitoring of the myocardium.

PMID- 14690736
TI  - Frizzled A, a novel angiogenic factor: promises for cardiac repair.
AB  - OBJECTIVE: Frizzled A is a very recent protein expressed in the cardiovascular
      hood by cardiomyocytes and by endothelial cells. This protein plays key roles in
      vitro in vascular cell proliferation and is able to induce an in vivo angiogenic
      response. Regarding these properties, we assess the hypothesis that Frizzled A
      could act in the healing process after myocardial infarction. METHODS: To
      investigate the role of Frizzled A, we established a transgenic mouse line
      overexpressing the protein and developed a model of myocardial infarction by
      coronary artery ligation. RESULTS: The incidence of cardiac rupture after
      myocardial infarction was reduced in transgenic mice (6.5 versus 26.4% in
      controls, n=165; P<0.01). Infarct sizes were smaller in transgenic mice (18% of
      left ventricle circumference versus 28.1% in control at day 30; P<0.001; n=6) and
      the cardiac function was improved (3800 +/- 370 versus 2800 +/- 840 mmHg/s
      dp/dtmax in controls, -2800 +/- 440 versus -1800 +/- 211 dp/dtmin in controls at
      day 15; P<0.001; n=6). Early leukocyte infiltration had decreased in transgenic
      mice during the first week (103 +/- 59 versus 730 +/- 463 cells/mm2 in controls
      at day 7; P<0.001; n=6) and the apoptotic index was decreased by 50% at day 7.
      Capillary density in the scar was higher in transgenic mice (290 +/- 103 versus
      104 +/- 43 vessels/mm2 in control at day 15; P<0.001) and vessels were more
      muscularized and mean lumen area was 3-fold higher (952 +/- 902 versus 313 +/-
      350 microm2 in control; P<0.001). CONCLUSION: Overexpression of Frizzled A
      reduced the infarct size, improved cardiac recovery, modified inflammatory
      response and amplified angiogenesis. For these reasons, this protein would be of
      interest for cardiac surgeons using angiogenic therapy (as gene or protein
      injection) in ischemic heart diseases in non-revascularizable patients.

PMID- 14690737
TI  - Passive external cardiac constraint improves segmental left ventricular wall
      motion and reduces akinetic area in patients with non-ischemic dilated
      cardiomyopathy.
AB  - OBJECTIVE: To verify changes in left ventricular (LV) volumes and regional
      myocardial wall motion after implantation of a textile cardiac support device
      (CSD) for passive external constraint in non-ischemic dilated cardiomyopathy.
      METHODS: In nine male patients participating in a non-randomized clinical trial
      LV volumes were determined and the segmental LV wall motion was studied by
      contrast-enhanced electron-beam CT in a sectionwise manner at three ventricular
      levels (base, middle and apex of ventricle) before and 32+/-6 months after CSD
      implantation. In 16 myocardial segments ejection fraction and wall thickening
      were measured semiautomatically after drawing the myocardial contours. The wall
      motion score index was calculated based on semiquantitative visual grading in
      each segment. RESULTS: The global LV volumes decreased significantly from 304.3
      +/- 90.9 to 231.5 +/- 103.9 ml at end-diastole and from 239.7 +/- 83.7 to 164.0
      +/- 97.7 at end-systole (P<0.05). Overall ejection fraction increased from 14.8
      +/- 8.2 to 25.7 +/- 17.1% (P<0.05). A segment-by-segment analysis demonstrated a
      significant increase of regional ejection fraction in the basal myocardium as
      well as in the mid-inferior, mid-inferolateral, and mid-anterolateral myocardium.
      Overall wall thickening increased from 16.4 +/- 13.3 to 24.2 +/- 18.1% (P<0.05),
      but without significant differences in a segment-by-segment comparison. The mean
      wall motion score index improved from 2.70 +/- 0.26 to 2.20 +/- 0.71 (P<0.05),
      with an increased wall motion in eight (89%) patients. A section-by-section
      analysis demonstrated significantly improved wall motion in the inferior and
      lateral segments at each ventricular level. Postoperatively, the number of
      akinetic and markedly hypokinetic segments decreased significantly (P<0.05) from
      56 (39%) to 26 (18%) and from 76 (53%) to 56 (37%), respectively. CONCLUSION: CSD
      implantation improves segmental wall motion, predominantly in the inferior and
      lateral myocardium, and reduces the number of akinetic and hypokinetic segments.

PMID- 14690738
TI  - The role of platelet derived growth factor in endomyocardial biopsies shortly
      after heart transplantation in relation to postoperative course.
AB  - OBJECTIVE: Platelet-derived growth factor (PDGF) plays an important role in
      structural alterations of blood vessels after heart transplantation (HTx). The
      aim of this study was to clarify the effect of peritransplant injury and
      postoperative complications on the expression of PDGF ligand and receptor.
      METHODS: Right ventricular endomyocardial biopsies were collected from 46
      patients before implantation, and then 1 and 2 weeks after HTx. According to the
      clinical course in the first postoperative year and to histopathological
      evaluation (based on the standardised 'International Society for Heart and Lung
      Transplantation' grading system) three groups were formed: (a) clinical
      uneventful course; (b) histologically and/or serologically proven cardiac or
      systemic infections; and (c) acute rejection episodes > or =grade 3A. Both,
      infections and rejections were detectable after the second postoperative week.
      The expression of PDGF AA/BB and PDGF receptors alpha/beta was examined
      immunohistochemically. The infiltrating cells were characterised by using
      monoclonal antibodies against CD3, CD4, CD8, CD57 and CD68. RESULTS: Only
      endothelial cells revealed a relevant expression of PDGF ligand and receptor.
      Prior to implantation there was no or only weak reactivity of single cells for
      all PDGF factors. One week after HTx a significantly increased immunoreactivity
      of all PDGF factors was observed in all groups. Two weeks after HTx the
      expression of PDGF AA in the infection group and the expression of all four PDGF
      factors in the rejection group remained significantly elevated. In contrast, in
      the group with an uneventful course there was no statistical difference in the
      expression of all the four PDGF factors. Compared with the uneventful group,
      there were significantly more CD3+ cells in the infection and rejection group at
      all three time points. Two weeks after HTx, the rejection group showed a
      significantly elevated number of CD3+ cells compared to the values before
      implantation. Two weeks after HTx there were significant more CD68+ cells in the
      infection and rejection group compared with before implantation. CONCLUSIONS: One
      week after HTx the peritransplant injury predominantly influences the endothelial
      expression of PDGF ligand and receptor. In the first postoperative week,
      expression of PDGF could be detected. The persistence of evaluated PDGF
      expression might be of prognostic value in terms of a risk for either infection
      or rejection. These patients should be carefully monitored.

PMID- 14690739
TI  - Maintenance of physiological coronary endothelial function after 3.3 h of
      hypothermic oxygen persufflation preservation and orthotopic transplantation of
      non-heart-beating donor hearts.
AB  - OBJECTIVE: The use of non-heart-beating donors (NHBD) might increase the number
      of grafts available for transplantation. Experiments on heart transplantation
      from NHBDs demonstrated the necessity for oxygenation during preservation to
      allow sufficient myocardial recovery. It has been shown that, after 16 min
      normothermic ischemia followed by 3.3-h hypothermic preservation, excellent
      myocardial and cardiovascular recovery is attained, if coronary oxygen
      persufflation (COP) is included in the preservation protocol. Here tests are
      presented on the recovery of coronary endothelium derived relaxation (EDR) of
      NHBD hearts after preservation including COP. METHODS: After 16 min normothermic
      ischemia, pig hearts were stored for 3.3 h at 0-1 degrees C in modified HTK plus
      COP (mBHTK+COP, n=6) or in two control groups without COP: (1) with mBHTK (n=6);
      and (2) with HTK (n=4). Following orthotopic transplantation and 3 h of
      reperfusion with full blood, coronary EDR was tested in vitro using Substance P
      (SP) under indomethacin for prostaglandin blockage. Additional tests were
      performed adding L-NIL to block the NO-production by iNOS or L-NNA to block total
      NO production. RESULTS: The EDR in percent of precontraction was 78 +/- 7% after
      mBHTK+COP and 77 +/- 20% (mBHTK) or 72 +/- 7% (HTK) in the controls without
      significant differences between the groups. Physiologic values of normal
      coronaries were 75 +/- 9%. L-NIL for blockage of NO-production by iNOS resulted
      in unchanged relaxations. After blockage of total NO production by L-NNA, the SP
      induced dilation was significantly reduced to 58 +/- 8% (mBHTK+COP) and to 48 +/-
      8% (mBHTK) or 55 +/- 13% (HTK) in the controls. CONCLUSIONS: Even after 16 min of
      warm ischemia followed by 3.3 h of preservation with gaseous oxygen
      persufflation, orthotopic transplantation, and reperfusion the endothelium
      derived coronary dilatation was unchanged from physiologic values and similar to
      the controls without COP. Blockage of NO production by L-NNA resulted in equal
      values of EDR with or without COP, while blockage of NO production by iNOS did
      not influence the EDR reaction. Thus COP preservation, which has been shown to
      allow excellent recovery of preserved NHBD hearts, caused no damage to the
      coronary EDR mechanisms.

PMID- 14690740
TI  - Neuroprotective effects of FK-506, L-carnitine and azathioprine on spinal cord
      ischemia-reperfusion injury.
AB  - OBJECTIVE: In our experimental study, we aimed to test the effect of FK506,
      azathioprine and L-carnitine on protection of spinal cord injury due to ischemia
      reperfusion. METHODS: Twenty-seven Sprague-Dawley male rats were randomly divided
      into five groups. They were subjected to spinal cord ischemia by clamping the
      abdominal aorta for 45 min. Thirty minutes before the aortic clamping, group I
      received 0.5 mg/kg FK506, group II received 100 mg/kg L-carnitine, group III
      received 4 mg/kg azathioprine, the fourth group was the control group and
      received only normal saline injection intravenously and the last group was the
      sham group. Neurological status was scored by using the Tarlov scoring system.
      Sections of the lumbar cord were harvested for histopathological grades (1-4),
      having regard to percentage of the apoptotic cells. RESULTS: Hind-limb motor
      function had recovered normally 48 h after the operation in all rats which
      received FK506, azathioprine and L-carnitine prophylactically. In contrast, all
      rats in the control group had deteriorated to paraplegia by 48 h after the
      operation (P<0.05). Histopathologic sections in the involved spinal cord segment
      showed that a greater number of motor neuron cells were preserved and there were
      less apoptotic cells in the rats that received FK506, azathioprine and L
      carnitine than those in control group. CONCLUSIONS: These results suggest that
      prophylactic use of FK506, azathioprine and L-carnitine protects motor neuron
      cells from ischemic spinal cord injury.

PMID- 14690741
TI  - Surgical nurse assistants in cardiac surgery: a UK trainee's perspective.
AB  - OBJECTIVE: To assess the impact of surgical nurse assistants on surgical training
      based on a comparative audit of case-mix and outcome of coronary
      revascularizations assisted by surgical nurse assistants vs. surgical trainees.
      METHODS: Relevant recent articles on Calman reform of specialist training and
      European working time directive (EWTD) on junior doctor working hours were
      reviewed for the discussion. For the audit prospectively entered data of elective
      and expedite first time coronary artery bypass grafting cases from 2000 to 2003
      were analysed. Group A (n=233, Consultant+Surgical nurse assistant), group B
      (n=1067, Consultant+Junior surgical trainee). Chi-square test, t-test and
      Fisher's test were used as appropriate for statistical analysis. RESULTS:
      Comparative preoperative variables were gender (P=0.8), body mass index (P=0.9),
      smoking (P=0.3), diabetes mellitus (P=0.2), hypertension (P=1), peripheral
      vascular disease (P=0.5), previous cerebrovascular accident (CVA)/transient
      ischemic attack (TIA) (P=0.3), renal dysfunction (P=0.4), preoperative rhythm
      disturbances (P=0.3), previous Q-wave myocardial infarction (MI) (P=0.4),
      Canadian Cardiovascular Society angina class (P=0.4), New York Heart Association
      heart failure class (P=0.4) and left ventricular function (P=0.4). Patients in
      group B were of higher risk due to age (P=0.01), coronary disease severity
      (P=0.05), left main stem disease (P=0.001), Parsonnet score (P=0.0001) and
      Euroscore (P=0.005. Regarding the myocardial protection technique, intermittent
      cross-clamp fibrillation was used more frequently in group A while antegrade
      retrograde cold blood cardioplegia and off-pump coronary artery bypass were used
      more in group B (P=0.0001). The cross-clamp (P=0.0001) and operation time
      (P=0.0001) were significantly lower in group A despite a comparable mean number
      of grafts (P=0.2). There was no significant difference in the immediate
      postoperative outcome ventilation time (P=0.2), intensive care unit stay,
      postoperative stay (P=0.2), re-exploration for bleeding (P=0.5), inotrope+intra
      aortic balloon pump (P=0.2), postoperative MI (P=0.9), postoperative rhythm
      disturbances (P=0.9), CVA/TIA (P=0.8), renal dysfunction (P=0.6), wound infection
      (P=0.7), sternal re-wiring (P=0.2), multi-organ failure (P=0.4) or mortality
      (P=0.1). CONCLUSIONS: Surgical nurse assistants can be used effectively in low
      risk cases without compromising postoperative results. However, initiatives to
      tackle the EWTD should be focused on areas that do not compromise the training
      needs of junior surgical trainees. An intermediate grade between the present
      senior house officer and registrar grades could be a way forward.

PMID- 14690742
TI  - Fast-tracking revisited: routine cardiac surgical patients need minimal intensive
      care.
AB  - OBJECTIVE: Following cardiac surgery, patients are transferred from the operating
      theatre to intensive care. This clinical environment has one nurse per patient
      and facilities for mechanical ventilation. Patients are kept in this setting
      until the following day. This practice has been challenged with early extubation
      of patients. At our institution we have established a fast-track policy including
      the following features: (1) patient selection; (2) operating list scheduling with
      fast-track patients first; (3) anaesthetic tailored to early extubation; (4)
      methodical procedure with warm cardiopulmonary bypass; (5) removal of the
      arterial line; (6) transfer from intensive care to a separate high dependency
      unit ('step-down') on the day of operation, where the ratio of nurse to patient
      is one to three and there are no ventilatory facilities and no invasive
      monitoring; or (7) to keep these patients on ICU but decrease the nurse to
      patient ratio. METHOD: The case notes of 572 patients who predominantly had
      myocardial revascularisation, undergoing this process from July 1996 to July 2000
      at our institution were reviewed. RESULTS: Mean EUROSCORE for the study group was
      1.42. The 30-day mortality rate for the study group was 0.34%, mean intensive
      care time was 5 h 52 min, mean time to extubation was 3 h 10 min, mean
      readmission rate to intensive care was 0.34% and mean hospital stay from day of
      operation (inclusive) was 5.65 days. This process increased our throughput by
      14.6% (compared to standard practices). COMMENT: This study demonstrates that
      transfer of appropriate patients to a high dependency area from intensive care
      following cardiac surgery is safe. It allows intensive care beds to be used by
      more than one patient each day and allows significant cost savings by reducing
      the nursing ratio per patient.

PMID- 14690743
TI  - The effectiveness of high dependency unit in the management of high risk thoracic
      surgical cases.
AB  - OBJECTIVE: To assess the effectiveness of high dependency unit (HDU) in the
      management of high-risk thoracic surgical cases at a single dedicated thoracic
      surgical unit. INTRODUCTION: There is a strong drive to improve postoperative
      management in a cost-effective way. The number of high-risk thoracic surgical
      procedures undertaken is increasing rapidly. The HDU can be an effective weapon
      in the armoury of thoracic surgeons to treat these patients effectively without
      the need for managing in the extreme environment of expensive intensive care
      beds. METHOD: Patients who had undergone lobectomy, pneumonectomy and
      oesophagectomy were included in the study, as they formed the bulk of the high
      risk thoracic surgical procedures undertaken by our unit. All data were collected
      retrospectively from case notes and computerised patient tracking system, for the
      period between April 2000 and March 2001. RESULT: One hundred and ninety-one
      lobectomies (174 for malignancy), 86 pneumonectomies and 50 oesophagectomies were
      performed during the time period of the study. Of these, 189 (99%) lobectomies,
      82 (95%) pneumonectomies and 47 (94%) oesophagectomies were electively admitted
      to HDU. The mean HDU stay was 21.8 h. Operation discharge time was 7.3 days for
      lung resections and 9.1 days for oesophagectomy. The overall 30-day mortality was
      1.9% for lobectomy, 11% for pneumonectomy and 2% for oesophagectomy. Two
      oesophagectomies, one lobectomy and three pneumonectomies had to be transferred
      from HDU to ITU for either mechanical ventilation or more invasive monitoring.
      Four pneumonectomies, two lobectomies and two oesophagectomies had to be
      readmitted to HDU with respiratory failure or cardiac instability. Of all the
      readmitted patients, one pneumonectomy and one lobectomy died. The causes of
      death were myocardial infarction, pulmonary embolism, adult respiratory distress
      syndrome and septicaemia. DISCUSSION: The above results clearly demonstrate that
      a well-equipped and properly manned HDU can greatly facilitate management of high
      risk cases with favourable outcome. It provides excellent pain control
      facilities, detects complications early and avoids unnecessary ITU admissions. It
      also provides an excellent training opportunity for both medical and nursing
      staff.

PMID- 14690744
TI  - Tracheal stenosis complicated with tracheoesophageal fistula.
AB  - OBJECTIVE: The aim of the present study was to evaluate the results of surgical
      treatment in patients with simultaneous occurrence of postintubation tracheal
      stenosis (TS) and tracheoesophageal fistula (TEF). METHODS: In the group of 51
      patients with postcannulation tracheal stenosis who underwent segmental
      resection, TEF was identified simultaneously in five (10%) of them. The mean age
      of the TS-TEF patients was 43 years (range 35-60 years). The patients underwent a
      single-stage operation during which TEF was sealed and resection of the stenotic
      tracheal segment was performed. RESULTS: The cause of TEF and of TS was
      artificial pulmonary ventilation by tracheostomy tube (n=4) or by endotracheal
      tube (n=1) with a simultaneous insertion of nasogastric tube. In one of the
      patients with tracheostomy the fistula resulted from an injury to the pars
      membranacea tracheae and the esophageal wall during tracheostomy. All the
      patients were respiring spontaneously before the surgical treatment. The mean
      length of the fistula was 24.0 mm (range 15-30 mm), the fistulae were located at
      the junction of the upper and middle third of the trachea. The mean length of the
      resected tracheal segment was 29.6 mm (range 26-32 mm). Postoperative
      complications were not observed in the group of the TS-TEF patients, none of them
      died. CONCLUSIONS: The method of choice of the surgical treatment of TEF
      associated with TS is a single-stage procedure in the patient who respires
      spontaneously.

PMID- 14690745
TI  - Melanoma associated antigen (MAGE)-A3 expression in Stages I and II non-small
      cell lung cancer: results of a multi-center study.
AB  - OBJECTIVES: Adjuvant immunotherapy is an innovative therapeutic option that might
      potentially improve outcome of early-stage non-small cell lung cancer. Melanoma
      associated antigen (MAGE)-A3 is a promising target for immunotherapy because it
      is exclusively presented on the cell surface of cancer cells and might be
      associated with an aggressive cancer phenotype. The present study was performed
      to determine the rate of MAGE-A3 expression in early-stage non-small cell lung
      cancer (NSCLC). PATIENTS AND METHODS: Primary tumor samples from 204 patients
      with operable clinical Stages I or II NSCLC were collected between March and
      November 2001. Pathological Stage was determined by the local pathologist in each
      of the 16 participating institutions. Tissue samples were stored immediately
      after surgery in a RNA-stabilizing solution and were frozen at -20 degrees C.
      MAGE-A3 expression was analyzed by detection of MAGE-A3 transcripts using reverse
      transcriptase polymerase chain reaction. RESULTS: MAGE-A3 expression was observed
      in 80 out of the 204 (39.2%) examined Stages I-II primary tumors. Stratification
      into UICC-Stages showed that 31 out of 105 (29.5%) Stage I non-small cell lung
      cancers and 49 out of 99 (49.5%) Stage II non-small cell lung cancers expressed
      MAGE-A3. In comparison to Stage I, the rate of MAGE-A3 positive tumors was
      significantly increased in Stage II (P=0.004; Chi-square test). CONCLUSION: The
      MAGE-A3 expression rate showed that a promising proportion of operable patients
      with early-stage non-small cell lung cancers are possible candidates for trials
      investigating adjuvant therapy with MAGE-A3 immunization. Currently, a phase two
      trial of adjuvant MAGE-A3 vaccination is in progress.

PMID- 14690746
TI  - Mediastinal Castleman disease with calcific deposits.

PMID- 14690747
TI  - Pulmonary azygous lobe: a potential obstacle during thoracoscopic sympathectomy.

PMID- 14690748
TI  - Right coronary artery aneurysm: transesophageal echocardiography view.

PMID- 14690749
TI  - Safety and efficacy of epidural cooling for regional spinal cord hypothermia
      during thoracoabdominal aneurysm repair.
AB  - Twenty-four consecutive patients underwent epidural cooling as an adjunct to
      elective thoracoabdominal aortic repair under moderate systemic hypothermia. One
      patient suffered from postoperative paraplegia (4%), and another died from
      subarachnoidal hemorrhage (4%). Details of the technique, the associated care,
      and the pitfalls will be discussed.

PMID- 14690751
TI  - Risk factors for sternal wound infection following coronary artery bypass graft
      surgery.

PMID- 14690752
TI  - A retrospective audit of long-term lower limb complications following leg vein
      harvesting for coronary artery bypass grafting.

PMID- 14690754
TI  - Anastomotic devices for coronary bypass: lethal complications have been
      previously reported!

PMID- 14690755
TI  - The EuroSCORE does well for a single surgeon outside Europe.

PMID- 14690757
TI  - The latissimus dorsi muscle previously divided in the course of thoracotomy for
      empyema cavity obliteration.

PMID- 14690758
TI  - Bronchioloalveolar carcinoma: myths and realities in the surgical management.

PMID- 14690760
TI  - Regulation of gene expression by biotin (review).
AB  - In mammals, biotin serves as coenzyme for four carboxylases, which play essential
      roles in the metabolism of glucose, amino acids, and fatty acids. Biotin
      deficiency causes decreased rates of cell proliferation, impaired immune
      function, and abnormal fetal development. Evidence is accumulating that biotin
      also plays an important role in regulating gene expression, mediating some of the
      effects of biotin in cell biology and fetal development. DNA microarray studies
      and other gene expression studies have suggested that biotin affects
      transcription of genes encoding cytokines and their receptors, oncogenes, genes
      involved in glucose metabolism, and genes that play a role in cellular biotin
      homeostasis. In addition, evidence has been provided that biotin affects
      expression of the asialoglycoprotein receptor and propionyl-CoA carboxylase at
      the post-transcriptional level. Various pathways have been identified by which
      biotin might affect gene expression: activation of soluble guanylate cyclase by
      biotinyl-AMP, nuclear translocation of NF-kappaB (in response to biotin
      deficiency), and remodeling of chromatin by biotinylation of histones. Some
      biotin metabolites that cannot serve as coenzymes for carboxylases can mimic
      biotin with regard to its effects on gene expression. This observation suggests
      that biotin metabolites that have been considered "metabolic waste" in previous
      studies might have biotin-like activities. These new insights into biotin
      dependent gene expression are likely to lead to a better understanding of roles
      for biotin in cell biology and fetal development.

PMID- 14690761
TI  - Effect of zinc deficiency on the mRNA expression pattern in liver and jejunum of
      adult rats: monitoring gene expression using cDNA microarrays combined with real
      time RT-PCR.
AB  - In the study presented here, the effect of zinc deficiency on mRNA expression
      levels in liver and jejunum of adult rats was analyzed. Feed intake was
      restricted to 8 g/day. The semi-synthetic diet was fortified with pure phytate
      and contained either 2 microg Zn/g (Zn deficiency, n = 6) or 58 microg Zn/g
      (control, n = 7). After 29 days of Zn depletion feeding, entire jejunum and liver
      were retrieved and total RNA was extracted. Tissue specific expression pattern
      were screened and quantified by microarray analysis and verified individually via
      real-time RT-PCR. A relative quantification was performed with the newly
      developed Relative Expression Software Tool Copyright on numerous candidate genes
      which showed a differential expression. This study provides the first comparative
      view of gene expression regulation and fully quantitative expression analysis of
      35 candidate genes in a non-growing Zn deficient adult rat model. The expression
      results indicate the existence of individual expression pattern in liver and
      jejunum and their tissue specific regulation under Zn deficiency. In addition, in
      jejunum a number of B-cell related genes could be demonstrated to be suppressed
      at Zn deficiency. In liver, metallothionein subtype 1 and 2 (MT-1 and MT-2) genes
      could be shown to be dramatically repressed and therefore represent putative
      markers for Zn deficiency. Expression results imply that some genes are expressed
      constitutively, whereas others are highly regulated in tissues responsible for Zn
      homeostasis.

PMID- 14690762
TI  - Intestinal absorption and metabolism of retinoyl beta-glucuronide in humans, and
      of 15-[14C]-retinoyl beta-glucuronide in rats of different vitamin A status.
AB  - In order to prove the hypothesis that humans and animals with adequate vitamin A
      status do not absorb and metabolize orally administered all-trans retinoyl beta
      glucuronide, unlabeled retinoyl glucuronide (0.1 mmol) was orally dosed to
      fasting well-nourished young men. Neither retinoyl glucuronide nor retinoic acid,
      a possible metabolite, appeared in the blood within 12 h after ingestion. Next,
      radiolabeled all-trans 15-[14C]-retinoyl beta-glucuronide was chemically
      synthesized by a new procedure, and fed orally to rats of different vitamin A
      status. Analysis of blood and other tissues 5 or 24 h after the dose, showed the
      presence of radioactivity ( approximately 0.5%) in the blood of vitamin A
      deficient rats, but not in sufficient rats. Livers of all rats contained small,
      but detectable amounts (0.3 to 1.1% of the dose) of radioactivity. The
      accumulation of radioactivity in the liver was highest in deficient rats.
      Analysis of the retinoids showed that the radioactivity in serum and liver was
      due to retinoic acid formed from retinoyl glucuronide. Within 24 h after the
      dose, 31 to 40% of the administered radioactivity was excreted in the feces, and
      2 to 4.7% of the dose was excreted in the urine. Results of the present studies
      show that oral administration of retinoyl beta-glucuronide did not give rise to
      detectable changes in blood retinoyl glucuronide and/or retinoic acid
      concentrations in humans or rats with adequate vitamin A status.

PMID- 14690763
TI  - Plasma circulating fibrinogen stability and moderate beer consumption.
AB  - MODERATE BEER CONSUMPTION (MBC) IS CARDIOPROTECTIVE: it positively influences
      plasma lipid levels and plasma antioxidant activity in beer-consuming
      individuals. The connection between MBC and blood coagulation is not clearly
      defined. Forty-two volunteers were equally divided into experimental (EG) and
      control (CG) groups following coronary bypass surgery. For 30 consecutive days,
      only patients of the EG consumed 330 mL of beer per day (about 20 g of alcohol).
      A comprehensive clinical investigation of 42 patients was done. Blood samples
      were collected before and after the investigation for a wide range of laboratory
      tests. The plasma fibrinogen was denatured with 8 M urea and intrinsic
      fluorescence (IF), hydrophobicity and differential scanning calorimetry (DSC)
      were used to reveal possible qualitative changes. After 30 days of moderate beer
      consumption, positive changes in the plasma lipid levels, plasma anticoagulant
      and plasma antioxidant activities were registered in patients of the EG group. In
      17 out of 21 patients of the same group, differences in plasma circulating
      fibrinogen's (PCF), secondary and tertiary structures were found. The stability
      of fibrinogen, expressed in thermodynamic parameters, has shown that the
      loosening of the structure takes place under ethanol and urea denaturation. Also
      fluorescence stability of PCF was decreased. No changes in the lipid levels,
      anticoagulant and antioxidant activity or changes in PCF were detected in
      patients of CG. In conclusion, for the first time after a short term of moderate
      beer consumption some qualitative changes in the plasma circulating fibrinogen
      were detected: differences in the emission peak response, fluorescence intensity
      and all thermodynamic data. Together, with the decrease in the PCF concentration
      it may lead to an elevation of the blood anticoagulant activity.

PMID- 14690764
TI  - Deoxynivalenol-induced mitogen-activated protein kinase phosphorylation and IL-6
      expression in mice suppressed by fish oil.
AB  - The trichothecene mycotoxin deoxynivalenol (DON) induces IgA hyperelevation and
      mesangial IgA deposition in mice that mimics the early stages of human IgA
      nephropathy (IgAN). Among potential mediators of this disease, interleukin-6 (IL
      6) is likely to play a particularly critical role in IgA elevation and disease
      exacerbation. Based on previous findings that dietary fish oil (FO) suppresses
      DON-induced IgAN, we hypothesized that FO inhibits the induction of IL-6
      expression by this mycotoxin in vivo and in vitro. Mice were fed modified AIN 93G
      diet amended with 7% corn oil (CO) or with 1% corn oil plus 6% menhaden fish oil
      (FO) for up to 8 weeks and then exposed acutely to DON by oral gavage. DON
      induced plasma IL-6 and splenic mRNA elevation in FO-fed mice were significantly
      suppressed after 8 weeks when compared to the CO-fed group. The effects of FO on
      phosphorylation of mitogen-activated protein kinases (MAPKs), critical upstream
      transducers of IL-6 up-regulation, were also assessed. DON-induced
      phosphorylation of extracellular signal regulated protein kinases 1 and 2
      (ERK1/2) and c-Jun N-terminal kinases 1 and 2 (JNK1/2) was significantly
      suppressed in spleens of mice fed with FO, whereas p38 was not. Splenic COX-2
      mRNA expression, which has been previously shown to enhance DON-induced IL-6, was
      also significantly decreased by FO, whereas plasma levels of the COX-2
      metabolite, prostaglandin E2, were not affected. To confirm in vivo findings, the
      effects of pretreatment with the two primary n-3 PUFAs in FO, eicosapentaenoic
      acid (20:5[n-3]; EPA) and docosahexaenoic acid, (22:6[n-3]; DHA), on DON-induced
      IL-6 expression were assessed in LPS-treated RAW 264.7 macrophage cells.
      Consistent with the in vivo findings, both EPA and DHA significantly suppressed
      IL-6 superinduction by DON, as well as impaired DON-induced ERK1/2 and JNK1/2
      phosphorylation. In contrast, the n-6 PUFA arachidonic acid (20:4[n-3]) had
      markedly less effects on these MAPKs. Taken together, the capacity of FO and its
      component n-3 PUFAs to suppress IL-6 expression as well as ERK 1/2 and JNK 1/2
      activation might explain, in part, the reported suppressive effects of these
      lipids on DON-induced IgA nephropathy.

PMID- 14690765
TI  - Non-schizophrenic psychoses: common and distinguishing features.

PMID- 14690766
TI  - An overview of the genetics of psychotic mood disorders.
AB  - This article presents a conceptual review of the genetic underpinnings of
      psychotic mood disorders. Both unipolar and bipolar forms of mood disorder
      sometimes feature psychotic symptoms. Some evidence from epidemiological research
      suggests that psychotic forms of mood disorder specifically might be heritable.
      Linkage studies of mood disorders in general have also provided some support for
      that notion, as have associated studies involving serotonin and dopamine genes
      and psychotic mood disorder. Some research suggests there might be a genetic
      connection between schizophrenia and bipolar disorder, undermining the
      Kraepelinian dichotomous classification of the psychoses. Future research should
      continue to examine psychotic forms of mood disorder using both epidemiological
      and molecular approaches.

PMID- 14690767
TI  - Categorical versus dimensional approaches to diagnosis: methodological
      challenges.
AB  - The arguments pitting categorical versus dimensional approaches to psychiatric
      diagnosis have been long ongoing with little sign of imminent resolution. We
      argue that categorical and dimensional approaches are fundamentally equivalent,
      but that one or other approach is more appropriate depending on the clinical
      circumstances and research questions being addressed. This paper aims to
      demonstrate (a) how these two approaches necessarily interdigitate, (b) to
      clarify the conditions under which one should utilize one approach over the
      other, and (c) to alert psychiatric clinicians and researchers to issues in the
      methodology literature that might facilitate their considerations. Using an
      example from the Infant Health and Development Program (IHDP), we illustrate the
      importance of using dimensional approaches for hypothesis testing, identify the
      problems with power and with interpretation that arise from employing a
      categorical approach, and underscore the importance of identifying the
      appropriate cutpoints when a categorical approach is necessitated. We argue that
      failure to utilize the correct approach under the appropriate circumstances can
      result in impaired clinical and research decision-making.

PMID- 14690768
TI  - Neuropsychological correlates of psychotic features in major depressive
      disorders: a review and meta-analysis.
AB  - Neuropsychological functioning has been a focus of study in psychotic disorders
      for many decades. These studies have focused primarily on schizophrenia, and less
      so on the affective psychoses, including psychotic major depression PMD. Several
      studies have provided evidence of cognitive dysfunction in PMD. However, these
      studies have utilized different assessment methods and instruments. Consequently,
      a clear picture of the nature and severity of cognitive impairment in PMD has yet
      to emerge in the literature. The current review seeks to provide a summary of the
      literature by composing a quantitative and qualitative review of the research to
      date on the cognitive impairment in psychotic major depression, specifically as
      it contrasts to those deficits observed in nonpsychotic depression. This review
      also provides a summary model of the pathophysiology of PMD to provide the
      necessary context to understanding the biological mechanisms of these
      impairments.

PMID- 14690769
TI  - Electrophysiological evidence of corollary discharge dysfunction in schizophrenia
      during talking and thinking.
AB  - Failure of corollary discharge, a mechanism for distinguishing self-generated
      from externally-generated percepts, has been posited to underlie certain positive
      symptoms of schizophrenia, including auditory hallucinations. Although originally
      described in the visual system, corollary discharge may exist in the auditory
      system, whereby signals from motor speech commands prepare auditory cortex for
      self-generated speech. While associated with sensorimotor systems, it might also
      apply to inner speech or thought, regarded as our most complex motor act. We had
      four aims in the studies summarized in this paper: (1) to demonstrate the
      corollary discharge phenomenon during talking and inner speech in human
      volunteers using event-related brain potentials (ERPs), (2) to demonstrate that
      the corollary discharge is abnormal in patients with schizophrenia, (3) to
      demonstrate the role of frontal speech areas in the corollary discharge during
      talking, and (4) to relate the dysfunction of the corollary discharge in
      schizophrenia to auditory hallucinations. Using EEG and ERP measures, we
      addressed each aim in patients with schizophrenia (DSM IV) and healthy control
      subjects. The N1 component of the ERP reflected dampening of auditory cortex
      responsivity during talking and inner speech in control subjects but not in
      patients. EEG measures of coherence indicated inter-dependence of activity in the
      frontal speech production and temporal speech reception areas during talking in
      control subjects, but not in patients, especially those who hallucinated. These
      data suggest that a corollary discharge from frontal areas where thoughts are
      generated fails to alert auditory cortex that they are self-generated, leading to
      the misattribution of inner speech to external sources and producing the
      experience of auditory hallucinations.

PMID- 14690770
TI  - Psychotic bipolar disorders: dimensionally similar to or categorically different
      from schizophrenia?
AB  - For over a century, clinicians have struggled with how to conceptualize the
      primary psychoses, which include psychotic mood disorders and schizophrenia.
      Indeed, the nature of the relationship between mood disorders and schizophrenia
      is an area of ongoing controversy. Psychotic bipolar disorders have
      characteristics such as phenomenology, biology, therapeutic response, and brain
      imaging findings, suggesting both commonalities with and dissociations from
      schizophrenia. Taken together, these characteristics are in some instances most
      consistent with a dimensional view, with psychotic bipolar disorders being
      intermediate between non-psychotic bipolar disorders and schizophrenia spectrum
      disorders. However, in other instances, a categorical approach appears useful.
      Although more research is clearly necessary to address the dimensional versus
      categorical controversy, it is feasible that at least in the interim, a mixed
      dimensional/categorical approach could provide additional insights into
      pathophysiology and management options, which would not be available utilizing
      only one of these models.

PMID- 14690771
TI  - Psychosis in body dysmorphic disorder.
AB  - Body dysmorphic disorder (BDD) has both psychotic and nonpsychotic variants,
      which are classified as separate disorders in DSM-IV (delusional disorder and a
      somatoform disorder). Despite their separate classification, available evidence
      indicates that BDD's delusional and nondelusional forms have many similarities
      (although the delusional variant appears more severe), suggesting that they may
      actually be the same disorder, characterized by a spectrum of insight. And
      contrary to what might be expected, BDD's delusional form, although classified as
      a psychotic disorder, appears to respond to serotonin-reuptake inhibitors alone.
      These and other data suggest that a dimensional view of psychosis (in particular,
      delusions) in these disorders may be more accurate than DSM's current categorical
      view. A dimensional model might also facilitate more consistent and accurate
      classification of other disorders that are likely characterized by a spectrum of
      insight, such as obsessive compulsive disorder, hypochondriasis, and anorexia
      nervosa. Further research is needed to better understand these classification
      issues, which likely have treatment implications.

PMID- 14690772
TI  - Treatment of non-schizophrenic disorders: focus on atypical antipsychotics.
AB  - Antipsychotics are commonly used for conditions other than schizophrenia, yet
      support for such use in the literature is unclear. This article reviews the
      literature on the pharmacologic treatment of specific types of non-schizophrenic
      disorders: those associated with psychotic depression, obsessive-compulsive
      disorder, body dysmorphic disorder, bipolar disorder, and dementia. It focuses on
      the evidence for using antipsychotics in these conditions, placing emphasis on
      atypical antipsychotics. Medline/HealthStar and PsycInfo databases were used to
      identify published trials and reports of antipsychotics used specifically for non
      schizophrenic disorders. Numerous studies were found supporting the use of
      atypical antipsychotics for non-schizophrenic disorders; however, with the
      exception of dementia, few randomized, double-blind controlled trials have been
      published examining the efficacy and safety of these agents in non-schizophrenic
      disorders. In general, most trials were restricted to short-term use as
      adjunctive therapy. The literature reviewed was primarily comprised of small open
      label trials, thus making it difficult to draw definitive conclusions. Despite
      the limitations of the trials reviewed, atypical antipsychotics represent a
      promising treatment modality when considering their improved side effect profile
      compared to conventional agents. Appropriate dosing and the use of antipsychotics
      in combination with psychosocial treatments are important treatment
      considerations. Due to the frequent clinical use of atypical antipsychotics as
      adjunctive therapy, well-designed trials of these agents in non-schizophrenic
      disorders are necessary.

PMID- 14690773
TI  - Psychosis of Alzheimer's disease: clinical characteristics and history.
AB  - The concept of psychosis of Alzheimer's disease and dementia is developed with
      respect to prevalence, incidence, clinical characteristics, clinical course, and
      potential response to treatment. Psychosis frequently occurs subsequent to the
      onset of dementia. Published prevalence estimates of psychosis in patients with
      AD range from 10 to 73% with an overall median of 34% within clinic populations,
      and from 7 to 20% in community and clinical trials populations depending on
      definitions used. Among people with AD who have no psychotic symptoms there
      appears to be an annualized incidence of psychosis of about 20% in outpatients,
      and a much higher rate in nursing home patients. Female gender, somewhat greater
      cognitive impairment among outpatients, somewhat lesser cognitive impairment
      among nursing home patients, and physical aggression are more associated with
      psychotic signs and symptoms than not. Right frontal hypometabolism and greater
      frontal neuropsychological deficits occur in AD patients with psychosis in
      comparison to those without. Among nursing home patients with dementia who have
      clinically significant agitation, the substantial majority have delusions or
      hallucinations. Among patients in nursing homes with dementia and psychosis,
      nearly two-thirds have persistent symptoms over at least 12 weeks, and among
      outpatient studies, hallucinations and delusions may persist in approximately 40
      50% over periods of 3 months to one year. There is some evidence that psychotic
      symptoms improve modestly with antipsychotic medication treatment. There is
      sufficient descriptive and empirical research to support the validity of a
      syndrome of psychosis of Alzheimer's disease.

PMID- 14690775
TI  - Infectious diseases in the 21st century: old challenges and new opportunities.
AB  - Infectious diseases are the confrontation of two worlds, the microbial world and
      the world of human physiology. Although these two worlds are as a whole governed
      by the same laws of nature, they show substantial differences: the
      microbiological world is 1000 times older, and was initiated by the development
      of the archaea, the 'living organisms of the extreme': its biomass and its
      diversity are immense - two to three billion species or 60% of the total biomass
      of the planet. The number of pathogens that adapted to man, however, is extremely
      limited - barely 1000. Thus, over billions of years, an evolution of the
      microbial world took place from 'early life', characterized by chemosynthesis, to
      the 'modern pathogens', and entailed a dramatic 'concentration' of life
      conditions and an adaptation towards a narrow range of requirements - those
      allowing survival in the human body. Within the last two centuries, these two
      slowly evolving systems, microbial life and human life, were profoundly modified
      in an unprecedented manner by a third player, human civilization, with its global
      impact on the environment through physical, chemical, societal, and climatic
      determinants. An appreciation of the evolution of infectious diseases in the 21st
      century and of the development of new diagnostic and therapeutic strategies
      therefore requires a full understanding of these three domains: human physiology,
      microbiology, and the environment. This review will put major emphasis on the
      environmental role of civilization on infectious diseases before considering new
      opportunities to combat them through novel and creative solutions.

PMID- 14690776
TI  - Human papillomavirus cervical infection in Guarani Indians from the rainforest of
      Misiones, Argentina.
AB  - OBJECTIVE: To evaluate the prevalence of human papillomavirus (HPV) cervical
      infection in women from the South American Guarani Indian tribe located in the
      rain forest of Misiones, north-eastern Argentina; a region with a high incidence
      of cervical carcinoma. METHODS: A cross-sectional cytological and HPV screening
      of sexually active Guarani women from nine Indian settlements was conducted.
      Demographic data, information about sexual behavior, and gynaecological history
      were recorded. Fresh cervical specimens from 239 patients were collected, of
      which 207 were included in this study. Cytology and microbiological detection
      were carried out by the Papanicolaou and Gram stain methods, respectively. HPV
      detection and typing were analyzed by PCR and RFLP. RESULTS: Pap smears in 96% of
      all patients showed an inflammatory pattern. A possible etiologic agent was found
      in 58% of cases: 52% Trichomonas vaginalis, 35% Gardnerella vaginalis and 13%
      Candida sp. Seven cases had cytological changes compatible with Low Grade
      Intraepithelial Lesion (LGSIL), one with High Grade Intraepithelial Lesion
      (HGSIL) and one in situ cervical cancer. The prevalence for generic HPV infection
      was 64% (133/207). Genotyping gave a 26% prevalence for HPV types 16/18, 13% for
      types 6/11 and 30% for other types, with nine mixed infections. CONCLUSION: This
      work reports for the first time the prevalence of cervical HPV infection in
      Guarani women. Nearly all Guarani women had some grade of cervical disease.
      Generic HPV infection prevalence was elevated (64%), with predominance of high
      risk types 16/18. A large variety of viral types was detected, including high to
      intermediate risk types not found previously in the region.

PMID- 14690777
TI  - In vitro inactivation of the rabies virus by ascorbic acid.
AB  - OBJECTIVE: The current recommended inactivating agent for the rabies virus, beta
      propiolactone (BPL) is very expensive and potentially carcinogenic. There is a
      need to evaluate alternative chemicals, which will inactivate the virus without
      affecting its antigenicity. In this study the effect of ascorbic acid on the
      infectivity of the rabies virus has been investigated. METHOD: Vero cell grown
      fixed rabies virus CVS strain was treated with 0.1 mg/ml, 0.5 mg/ml and 1mg/ml
      final concentrations of ascorbic acid and 5 microg/ml of copper sulfate and kept
      at 4 degrees C along with untreated virus material. Each aliquot was titrated
      after various intervals for viral infectivity using both mice inoculation and
      titration in vero cells. The antigenicity of the virus material was determined by
      antibody induction in mice and modified NIH tests in parallel with virus material
      inactivated with a 1:4000 concentration of BPL. RESULTS: An optimal concentration
      of 0.5 mg/ml of ascorbic acid and 5 microg/ml of copper sulfate completely
      inactivated the virus after 72 hours. The inactivated virus retained good
      antigenicity and potency value, which was comparable with using BPL. CONCLUSION:
      These findings suggest that ascorbic acid can be used as an inactivating agent
      for fixed rabies virus grown in cell culture particularly for the preparation of
      diagnostic reagents. Further studies are required to evaluate its effect on the
      cell associated virus, probable therapeutic potential and feasibility of
      replacing BPL in production of inactivated rabies vaccine.

PMID- 14690778
TI  - Containing a haemorrhagic fever epidemic: the Ebola experience in Uganda (October
      2000-January 2001).
AB  - INTRODUCTION: The Ebola virus, belonging to the family of filoviruses, was first
      recognized in 1976 when it caused concurrent outbreaks in Yambuku in the
      Democratic Republic of Congo (DRC), and in the town of Nzara in Sudan. Both
      countries share borders with Uganda. A total of 425 cases and 224 deaths
      attributed to Ebola haemorrhagic fever (EHF) were recorded in Uganda in 2000/01.
      Although there was delayed detection at the community level, prompt and efficient
      outbreak investigation led to the confirmation of the causative agent on 14
      October 2000 by the National Institute of Virology in South Africa, and the
      subsequent institution of control interventions. CONTROL INTERVENTIONS: Public
      health interventions to contain the epidemic aimed at minimizing transmission in
      the health care setting and in the community, reducing the case fatality rate due
      to the epidemic, strengthening co-ordination for the response and building
      capacity for on-going surveillance and control. Co-ordination of the control
      interventions was organized through the Interministerial Committee, National
      Ebola Task Force, District Ebola Task Forces, and the Technical Committees at
      national and district levels. The World Health Organization (WHO) under the
      Global Outbreak Alert and Response Network co-ordinated the international
      response. The post-outbreak control interventions addressed weaknesses prior to
      outbreak detection and aimed at improving preparations for future outbreak
      detection and response. Challenges to control efforts included inadequate and
      poor quality protective materials, deaths of health workers, numerous rumors and
      the rejection of convalescent cases by members of the community. CONCLUSIONS:
      This was recognized as the largest reported outbreak of EHF in the world. Control
      interventions were very successful in containing the epidemic. The community
      structures used to contain the epidemic have continued to perform well after
      containment of the outbreak, and have proved useful in the identification of
      other outbreaks. This was also the first outbreak response co-ordinated by the
      WHO under the Global Outbreak Alert and Response Network, a voluntary
      organization recently created to co-ordinate technical and financial resources to
      developing countries during outbreaks.

PMID- 14690779
TI  - Well diffusion for antifungal susceptibility testing.
AB  - INTRODUCTION: The increasing clinical and microbiologic resistance of Candida
      spp. isolates to several antifungal agents is becoming a serious problem. It is
      now reasonable to propose the use of antifungal susceptibility testing in Candida
      spp. isolates from patients who have failed conventional therapy, before the
      selection of an empirical therapy. METHODS: One hundred and fifty eight isolates
      of Candida spp. were evaluated simultaneously by broth microdilution (NCCLS
      standard) and well diffusion testing (WD), a diffusion method similar to disc
      diffusion. RESULTS: According to the Wilcoxon Signed Ranks test performed, there
      was no significant difference (p>0.05) between both methodologies for all
      antifungal agents tested (fluconazole, itraconazole, posaconazole, caspofungin
      and amphotericin B, with C. tropicalis, C. krusei, C. dubliniensis, C.
      guillermondii, C. parapsilosis, C. albicans and C. glabrata). A significant
      difference was observed when comparing well diffusion with NCCLS for fluconazole
      WD 80% (p=0.008) in C. glabrata, as well as WD 80% (p=0.002) and WD 50% (p=0.002)
      in C. albicans. CONCLUSIONS: The well diffusion test is simple, easy to
      reproduce, inexpensive, easy both to read and interpret, and has a good
      correlation to the reference NCCLS microdilution test and may represent an
      alternative method for antifungal drug susceptibility testing of Candida spp.,
      mainly in laboratories with few resources.

PMID- 14690780
TI  - Implementation of clinical practice guidelines for upper respiratory infection in
      Thailand.
AB  - OBJECTIVE: To determine the effectiveness of implementing clinical practice
      guidelines (CPG) on antibiotic prescribing for adults with upper respiratory
      infection (URI) in terms of the changes in diagnosis and prevalence and patterns
      of antibiotic prescribing. METHODS: The CPG on antibiotic treatments for adults
      with URI published in the Annals of Internal Medicine 2001; 134: 479-52 were
      considered to be of high quality and applicable to Thai patients. A one-page
      clinical practice protocol in Thai was prepared from these guidelines. The
      dissemination strategy provided CPG and clinical practice protocol to 12 general
      practitioners in Siriraj Social Security Program in Bangkok during interactive
      educational meetings in April 2001. The information on 837 URI episodes from
      January to March (pre-CPG phase) and 774 URI episodes during May to July (post
      CPG phase) were extracted from the patients' medical records. Telephone follow up
      for patients without antibiotics in the post-CPG phase was also attempted.
      RESULTS: Changes in the post-CPG period included (1) The diagnosis of URI was
      used less frequently whereas the diagnosis of common cold, pharyngitis and acute
      bronchitis were used more frequently (p<0.05). (2) Antibiotic use fell from 74.0%
      to 44.1% (p<0.001). (3) Fewer prescriptions for amoxicillin, roxithromycin, co
      trimoxazole and doxycycline, and more for penicillin V (p<0.05). Patients (n=97)
      not given antibiotics reported recovery in 83.5% and improvement in 16.5%.
      CONCLUSION: A locally prepared clinical practice protocol based on US CPG for
      appropriate antibiotic use for URI combined with interactive educational meetings
      is effective in promoting appropriate diagnosis and antibiotic therapy in an
      ambulatory setting in a tertiary care hospital in Thailand.

PMID- 14690781
TI  - Pneumococcal bacteremia in a single center in Argentina.
AB  - OBJECTIVE: To determine the clinical and microbiologic characteristics of
      pneumococcal bacteremia at Sanatorio Mitre, Buenos Aires, Argentina. METHODS: One
      hundred-and-seven episodes of pneumococcal bacteremia were prospectively analyzed
      from 1993 to 1998. Demographics, clinical and microbiological variables were
      studied. RESULTS: Eighty-one patients (76%) were adults and 26 children (24%).
      Most cases (98%) were acquired in the community. Seventy-nine patients (74%) had
      at least one underlying condition. The primary source of bacteremia was found in
      91 patients (85%), the lungs being the most common source. Streptococcus
      pneumoniae was isolated from one sterile site other than the primary focus in 25
      patients (23%). Eighty-five (79%) of the Streptococcus pneumoniae were
      susceptible to penicillin and 22 (21%) showed intermediate or high resistance to
      penicillin and 2% were additionally resistant to ceftriaxone. Initial
      antimicrobial therapy was appropriate in 95% of the cases. The overall mortality
      was 21%, however adults admitted to the intensive care unit (ICU) had higher
      mortality (81%). No patients under 14 years old died. Multivariate analysis
      showed that age and recovery of the organisms from a sterile site other than the
      primary focus were statistically significant predictors of mortality. CONCLUSION:
      Bacteremic pneumococcal infections continue to be an important worldwide problem
      causing morbidity and high mortality despite supportive care and appropriate
      antimicrobial therapy.

PMID- 14690782
TI  - Cefepime-induced encephalopathy.

PMID- 14690784
TI  - Do irradiated foods cause or promote colon cancer?

PMID- 14690785
TI  - Niacin and carcinogenesis.
AB  - The dietary status of niacin (vitamin B3) has the potential to influence DNA
      repair, genomic stability, and the immune system, eventually having an impact on
      cancer risk, as well as the side effects of chemotherapy in the cancer patient.
      In addition to its well-known redox functions in energy metabolism, niacin, in
      the form of NAD, participates in a wide variety of ADP-ribosylation reactions.
      Poly(ADP-ribose) is a negatively charged polymer synthesized, predominantly on
      nuclear proteins, by at least seven different enzymes. Poly(ADP-ribose)
      polymerase-1 (PARP-1) is responsible for the majority of polymer synthesis and
      plays important roles in DNA damage responses, including repair, maintenance of
      genomic stability, and signaling events for stress responses such as apoptosis.
      NAD is also used in the synthesis of mono(ADP-ribose), often on G proteins, with
      poorly understood roles in signal transduction. Last, NAD and NADP are required
      for the synthesis of cyclic ADP-ribose and nicotinic acid adenine dinucleotide
      (NAADP), two mediators of intracellular calcium signaling pathways. Disruption of
      any of these processes has the potential to impair genomic stability and
      deregulate cell division, leading to enhanced cancer risk. There are various
      sources of evidence that niacin status does have an impact on cancer risk,
      including animal models of leukemogenesis and skin cancer, as well as
      epidemiological data from human populations.

PMID- 14690786
TI  - Glycemic index, glycemic load, and incidence of endometrial cancer: the Iowa
      women's health study.
AB  - Although specific foods or nutrients have not been linked consistently with risk
      of endometrial cancer, obesity and diabetes are associated with increased risk.
      These conditions may be influenced by the glycemic index or load of the usual
      diet. We therefore examined the association of glycemic index and load measured
      at baseline using a food frequency questionnaire in a cohort of 23335
      postmenopausal women. Over 15 yr of follow-up, we identified 415 incident
      endometrial cancers. The average glycemic index was not associated with
      endometrial cancer occurrence. After adjustment for other risk factors, the
      average glycemic load was positively but weakly associated, with a relative risk
      of 1.24 (95% CI = 0.90-1.72) for the highest versus lowest quintile of glycemic
      load (P for trend = 0.08). This relative risk was 1.46 (95% CI = 1.02-2.08; P for
      trend = 0.02) among nondiabetic women, but the trend was in the opposite
      direction among diabetic women. Our study indicates that a higher dietary
      glycemic load may be a risk factor for endometrial cancer incidence in
      nondiabetic women.

PMID- 14690787
TI  - Selenium supplementation enhances low selenium levels and stimulates glutathione
      peroxidase activity in peripheral blood and distal colon mucosa in past and
      present carriers of colon adenomas.
AB  - Selenoproteins such as glutathione peroxidases (GPx), thioredoxin reductases
      (TrxR), and selenoprotein P (SePP) contain molecular selenium in form of
      selenocysteines within their active center. They are involved in the defense of
      reactive oxygen species, which otherwise may cause DNA damage and alterations of
      protein function. Selenium intake has been linked to colon carcinogenesis in
      epidemiological and interventional studies. In a double-blinded, placebo
      controlled trial, we demonstrate that carriers of colon adenomas present with low
      basal serum levels of selenium and plasma glutathione peroxidase (pGPx) activity
      before treatment, but both parameters can be normalized by interventional
      selenium supplementation. GPx activity in colon mucosa was enhanced in the verum
      group, albeit this had only borderline significance. No change of activity was
      observed for mucosal TrxR activity on selenium supplementation. In summary, our
      results confirm the existence of low selenium levels in patients prone to colon
      adenomas and show that by selenium supplementation this can be normalized. If
      prospective trials confirm that selenium supplementation reduces colon cancer
      incidence rates, it may be concluded that selenium supplementation should be
      recommended for patients at risk.

PMID- 14690788
TI  - Raw and cooked vegetables, fruits, selected micronutrients, and breast cancer
      risk: a case-control study in Germany.
AB  - In 1998-2000, a case-control study of breast cancer was conducted in Heidelberg,
      Germany. Three hundred ten consecutively recruited cases with primary breast
      cancer were matched according to 10-yr age groups to 353 controls with conditions
      unrelated to diet or endocrine disorders. Intake of raw vegetables, total
      vegetables, and whole-grain products was inversely associated with breast cancer
      risk (highest vs. lowest quartile adjusted odds ratio [OR] 0.51, 95% confidence
      interval [CI] 0.31-0.84; OR = 0.62, 95% CI = 0.38-1.02; and OR = 0.57; 95% CI =
      0.34-0.95, respectively). Also, high intake of some selected vitamins and
      minerals possessing putative DNA-stabilizing properties displayed significant
      inverse risk associations. Adjusted ORs were as follows: vitamin C (OR = 0.49,
      95% CI = 0.2-0.88), folate equivalents (OR = 0.47, 95% CI = 0.25-0.88), b
      carotene (OR = 0.46, 95% CI = 0.27-0.80), zinc (OR = 0.35, 95% CI = 0.15-0.78),
      and copper (OR = 0.51, 95% CI = 0.31-1.03). In contrast, no significant
      association with risk was seen for an increased intake of fruits, cooked
      vegetables, fiber, calcium, manganese, or iron. In this population of German
      women, components of raw vegetables and some micronutrients appear to decrease
      breast cancer risk.

PMID- 14690790
TI  - Baseline nutritional assessment in advanced cancer patients receiving palliative
      chemotherapy.
AB  - Depletion of nutritional reserves and significant weight loss can lead to an
      increased risk of morbidity, reduced chemotherapy response, and shorter survival
      in patients with cancer. Weight loss and malnutrition are recognized to result
      from multifactorial processes, which if assessed and managed appropriately may
      lead to improved treatment outcome. Numerous methodologies are used for the
      assessment of nutritional status. However, it remains unclear which of these
      tools is the most appropriate in the setting of cancer chemotherapy. The aim of
      this study was to investigate the use of various fundamental assessment tools
      that could be applied to the routine clinical evaluation of nutritional status in
      patients with advanced solid malignancies before treatment with palliative
      chemotherapy. We investigated the interrelationships between biochemical indices,
      anthropometric measures, and a nutritional screening tool, the Mini-Nutritional
      Assessment, in 73 patients. Many of these measures were highly interrelated, but
      the baseline history of weight loss in these patients was strongly correlated to
      the Mini-Nutritional Assessment (MNA) score (P < 0.0005). In turn, baseline
      weight loss and the MNA score were strongly correlated to serum C-reactive
      protein (a marker of acute-phase response). In some patients, malnutrition was
      linked to disease- or treatment-related upper digestive tract morbidity. Testing
      for the serum concentration of C-reactive protein at baseline may identify a
      subset of patients for whom a decline in nutritional status is linked to the
      presence of an active inflammatory response, a recognized precursor of cachexia

PMID- 14690789
TI  - Cruciferous vegetables, mushrooms, and gastrointestinal cancer risks in a
      multicenter, hospital-based case-control study in Japan.
AB  - We assessed the possible association of gastrointestinal cancers with cruciferous
      vegetables and mushrooms in a multicenter, hospital-based case-control study in
      an agricultural area of Japan. One hundred forty-nine cases and 287 controls for
      stomach cancer and 115 cases and 230 controls for colorectal cancer were matched
      by age, sex, and residential area. In stomach cancer, the protective effect of
      vegetables (consumption of total vegetable) was obscure, but it became clearer
      when we examined specific kinds of vegetables. Marginal associations were
      observed in the group of the highest consumption of Chinese cabbage (odds ratio
      [OR] = 0.61; 95% confidence interval [CI] = 0.35-1.07), broccoli (OR = 0.60; 95%
      CI = 0.34-1.08), Hypsizigus marmoreus (Bunashimeji) (OR = 0.57; 95% CI = 0.31
      1.04) and Pholita nameko (Nameko) (OR = 0.56; 95% CI = 0.30-1.06). In colorectal
      cancer, we observed decreased risks from the highest tertile of total vegetables
      (OR = 0.22; 95% CI = 0.08-0.66) and low-carotene-containing vegetables (OR =
      0.28; 95% CI = 0.08-0.77), and inverse associations were observed in the group of
      the highest consumption of broccoli (OR = 0.18; 95% CI = 0.06-0.58). Although the
      sample size was limited, subgroup analyses showed that the associations differed
      with the histopathological subtype. These findings suggest that cruciferous
      vegetables decrease the risk of both stomach and colorectal cancer, and that
      mushrooms are associated with a decreased risk of stomach cancer.

PMID- 14690791
TI  - Egg consumption and mortality from colon and rectal cancers: an ecological study.
AB  - The relation between egg consumption and mortality from colon and rectal cancers
      remains unclear and was investigated in this study. Colon and rectal cancer
      mortality data, mostly around 1993-94 and egg consumption data in nine time
      periods (1964-94) in 34 countries were derived from World Health Organization and
      Food and Agriculture Organization, respectively. Egg consumption was
      significantly and positively correlated with mortality from colon and rectal
      cancers in both sexes in most of the nine time periods. The correlations were
      generally stronger for colon cancer (r = 0.39 to 0.63 in men and r = 0.33 to 0.65
      in women) than for rectal cancer (r = 0.18 to 0.49 in men and r = 0.08 to 0.45 in
      women). After adjustment for confounding factors, egg consumption was still
      significantly and positively associated with mortality from colon cancer in the
      earliest five time periods (1964-84) (P = 0.046 to 0.017 in men and P = 0.034 to
      0.014 in women) and rectal cancer in the latest five time periods except for the
      last time period (1982-91) (P = 0.046 to 0.024 in men and P = 0.045 to 0.026 in
      women). This study suggested that egg consumption was associated with an
      increased risk of colon and rectal cancers at the population level

PMID- 14690792
TI  - Energy balance and rectal cancer: an evaluation of energy intake, energy
      expenditure, and body mass index.
AB  - Lack of energy balance, or greater energy intake than expenditure as indicated by
      a large body mass index (BMI), has been associated with colon cancer, although
      less is known about its association with rectal cancer. In this study, we
      examined the association between BMI, energy intake, and energy expenditure and
      their combined effect on rectal cancer risk. A population-based case-control
      study was conducted in Utah and Northern California. Incident cases (n = 952) of
      rectal cancer and population-based controls (n = 1205) were interviewed between
      1997 and 2002 to obtain detailed information on body size, dietary intake, and
      physical activity patterns. BMI (kg/m(2)) was not associated with rectal cancer
      in either men or women. Participation in vigorous leisure-time physical activity
      over the past 20 yr was associated with a significant 40% reduction in rectal
      cancer risk. Energy intake was associated significantly with increased risk of
      rectal cancer, especially among people whose diagnosis was prior to age 60 yr
      (odds ratio [OR] = 3.9; 95% confidence interval [CI] = 1.7-9.1 for men; OR = 2.8;
      95% CI = 1.1-7.2 for women). There was a significant interaction between energy
      intake and energy expenditure, although not between BMI and either energy intake
      or energy expenditure. These data suggest that large BMI, an indicator of lack of
      energy balance, is not an important component of the etiology of rectal cancer.
      However, both physical activity and energy intake were significantly associated
      with rectal cancer risk. These data suggest that energy expenditure and energy
      intake alter rectal cancer risk through mechanisms other than energy balance.

PMID- 14690793
TI  - Effects of green tea and high-fat diet on arachidonic acid metabolism and
      aberrant crypt foci formation in an azoxymethane-induced colon carcinogenesis
      mouse model.
AB  - Excessive fat consumption is a risk factor for colon carcinogenesis, and green
      tea consumption may reduce the risk of colon and other cancers. The current study
      was designed to investigate the effects of green tea and a high-fat diet on
      arachidonic acid metabolism and aberrant crypt foci formation in an azoxymethane
      (AOM)-induced colon carcinogenesis mouse model. We also determined whether green
      tea consumption altered the size of regional fat pads. CF-1 female mice were
      maintained on either a high-fat (20% corn oil) or a low-fat (5% corn oil) diet.
      AOM was given subcutaneous at a dose of 7.5 mg/kg body weight at 6 wk and then a
      dose of 10 mg/kg at 7 wk of age. Two weeks after the second AOM injection, 0.6%
      green tea (6 mg tea solids/ml) was given as the drinking fluid and continued for
      10 wk until the experiment was terminated. In the AOM-treated mice not receiving
      green tea, the high-fat diet significantly enhanced colonic levels of 5
      lipoxygenase, leukotriene A4 hydrolase, and leukotriene B4, but it did not
      significantly alter prostaglandin E2 levels and aberrant crypt foci formation. In
      AOM-treated mice on the high-fat diet, green tea significantly decreased colonic
      levels of cytosolic phospholipase A2, 5-lipoxygenase, and leukotriene B4; green
      tea treatment also decreased the number of aberrant crypt foci (P < 0.05). The
      weights of parametrial and retroperitoneal fat pads were increased by the high
      fat diet and decreased by green tea treatment. The current results indicate that
      green tea consumption and dietary fat modulate 5-lipoxygenase-dependent pathway
      of arachidonic acid metabolism during AOM-induced colon carcinogenesis. Green tea
      inhibits ACF formation in mice on a high corn oil diet, suggesting its possible
      inhibitory effect on colon carcinogenesis in populations such as those in Western
      countries that consume high amounts of fat.

PMID- 14690794
TI  - Comparison of the chemopreventive efficacies of 1,4
      phenylenebis(methylene)selenocyanate and selenium-enriched yeast on 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone induced lung tumorigenesis in A/J
      mouse.
AB  - Epidemiological studies, clinical intervention trials (including the trial with
      selenium-enriched yeast by Clark et al. JAMA 276, 1957, 1996) and assays in
      laboratory animals provide evidence for a protective role of selenium against the
      development of several cancers, including lung cancer. We have demonstrated that
      selenium in the form of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) is a
      promising chemopreventive agent in the A/J mouse lung tumor model induced with
      the carcinogenic tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanone (NNK); under identical conditions, selenomethionine (SM), a component
      of selenium-enriched yeast, had no effect. The lack of an effect of SM suggests
      that other forms of selenium, or selenium-enriched yeast as a whole, are
      essential for lung cancer prevention; moreover, various species may respond
      differently to a given form of selenium. Therefore, in this study, we compared
      the chemopreventive efficacies of p-XSC with selenium-enriched yeast. Groups of 5
      wk-old mice were fed either control diet or experimental diet containing p-XSC (5
      or 10 ppm as selenium, equivalent to 20% and 40% maximum tolerated dose [MTD],
      respectively) or selenium-enriched yeast (5 or 10 ppm). Beginning at Wk 7, each
      mouse received NNK (3 mmol) in 0.1 ml cottonseed oil by intragastric intubation,
      once weekly for 8 wk. Twenty-six weeks after the first NNK administration, mice
      were killed and tumors in lung and forestomach were counted. p-XSC at 5 and 10
      ppm doses significantly reduced lung tumor induction by NNK from 10.4 -/+ 6.0
      (multiplicity) to 2.7 -/+ 1.5 (P < 0.001) and 1.8 -/+ 2.0 (P < 0.0001)
      respectively, whereas selenium-enriched yeast had no effect. p-XSC at 10 ppm also
      significantly reduced the incidence level from 96% to 68% (P < 0.01). The amounts
      of selenium that reach the target organ (lung) after dietary administration of p
      XSC (326 -/+ 69 ng Se/g lung tissue) were significantly higher than that from
      selenium-enriched yeast (34 -/+ 8.5 ng Se/g lung tissue). However, the levels of
      selenium in plasma from selenium-enriched yeast (620 -/+ 54 ng Se/g plasma) were
      twofold higher than those from p-XSC (355 -/+ 85 ng Se/g plasma). In biochemical
      studies, p-XSC was shown to significantly inhibit formation of O6-methylguanine
      (O6-MG) and 7-methylguanine (7-MG) in the lungs and livers of mice treated with
      NNK. The lack of effect of selenium-enriched yeast on these lesions agrees with
      the results of the bioassay. Collectively, the results of this study clearly
      indicate that as a chemopreventive agent, p-XSC is superior to selenium-enriched
      yeast under the conditions of the present protocol. The inhibition of DNA
      methylation and the significantly higher retention of selenium from p-XSC as
      compared with selenium-enriched yeast in the target organ may in part account for
      the inhibition of lung tumorigenesis.

PMID- 14690796
TI  - Cell cycle dysregulation induced by cytoplasm of Lactococcus lactis ssp lactis in
      SNUC2A, a colon cancer cell line.
AB  - The anticancer effect of cytoplasmic fraction from Lactococcus lactis ssp.
      lactis, which had showed strong antiproliferative activity against SNUC2A human
      colon cancer cell line in the previous study, was investigated. The proliferation
      of SNUC2A was inhibited by the treatment with cytoplasmic fraction of Lactococcus
      lactis ssp. lactis in a dose-dependent and partially reversible manner. After
      exposure to the cytoplasmic fraction of Lc. lactis for 72 h, strong
      antiproliferative activity was efficiently induced through S-phase accumulation
      in SNUC2A cells. Analysis of cell cycle regulatory proteins demonstrated that the
      cytoplasmic fraction enhanced the levels of p21CIP1 and cyclin A, decreased
      cyclin E protein, and slightly reduced the activity of cyclin-dependent kinase 2
      (CDK2).

PMID- 14690795
TI  - Anthocyanin-rich extract from Aronia meloncarpa E induces a cell cycle block in
      colon cancer but not normal colonic cells.
AB  - Anthocyanin-rich extracts, potent antioxidants and commercially available food
      coloring agents, have been reported to inhibit growth of various cancer cell
      lines. We investigated the effect of semipurified anthocyanin-rich extract from
      fruits of Aronia meloncarpa, on normal colon and colon cancer cell lines. A 24-h
      exposure to 50 mg monomeric anthocyanin/ml of Aronia extract resulted in 60%
      growth inhibition of human HT-29 colon cancer cells. The treated cells showed a
      blockage at G1/G0 and G2/M phases of the cell cycle. The cell cycle arrest
      coincided with an increased expression of the p21WAF1 and p27KIP1 genes and
      decreased expression of cyclin A and B genes. Prolonged exposure to the extract
      resulted in no further change in the cell number, indicating a cytostatic
      inhibition of cell growth. NCM460 normal colon cells demonstrated <10% growth
      inhibition at the highest concentration of 50 mg/ml extract. A 35% decrease in
      the cyclooxygenase-2 gene expression was observed within 24 h of exposure of HT
      29 cells but did not translate into decreased protein levels or protein activity.
      These results support the need for further research to identify the specific
      component(s) in this extract that suppress cancer cell growth and the genes
      affected by these natural compounds.

PMID- 14690797
TI  - Sodium butyrate inhibits cell growth and stimulates p21WAF1/CIP1 protein in human
      colonic adenocarcinoma cells independently of p53 status.
AB  - Butyric acid, one of the short-chain fatty acids produced by microbial
      fermentation in the colon, exhibits antiproliferative activities in various
      cancer cell lines. The initial objective of the study was to assess whether the
      effect of sodium butyrate (NaB) on cell growth differed by p53 status of the
      cells. Four human colorectal adenocarcinoma cell lines were used: HT29 (p53 point
      mutation), Caco2 (p53 truncation), LS513 (p53 wild type), and Lovo (p53 wild
      type). NaB significantly inhibited cell growth in all four cell lines. NaB
      arrested HT29 and LS513 cells in G0/G1 and Caco2 and Lovo in G2-phase. A second
      objective was to determine whether NaB similarly affected the cyclin-dependent
      kinase inhibitor, p21WAF1/CIP1. In all cell lines, p21 mRNA levels were
      immediately elevated after NaB exposure, and p21 protein levels were increased
      within 6 h. NaB increased p21 promoter activity in both Caco2 and Lovo,
      suggesting p53 independence. NaB did not influence p21 mRNA stability. Although
      three DNase I hypersensitivity sites were identified in the region of the p21
      gene, induction of p21 mRNA by NaB was not accompanied by relaxation of the
      chromatin in the region of the p21 gene.

PMID- 14690798
TI  - Effect of dietary constituents with chemopreventive potential on adduct formation
      of a low dose of the heterocyclic amines PhIP and IQ and phase II hepatic
      enzymes.
AB  - We conducted a study to evaluate dietary chemopreventive strategies to reduce
      genotoxic effects of the carcinogens 2-amino-1-methyl-6-phenyl-imidazo[4,5
      b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). PhIP and IQ
      are heterocyclic amines (HCAs) that are found in cooked meat and may be risk
      factors for cancer. Typical chemoprevention studies have used carcinogen doses
      many thousand-fold higher than usual human daily intake. Therefore, we
      administered a low dose of [14C]PhIP and [3H]IQ and utilized accelerator mass
      spectrometry to quantify PhIP adducts in the liver, colon, prostate, and blood
      plasma and IQ adducts in the liver and blood plasma with high sensitivity. Diets
      supplemented with phenethylisothiocyanate (PEITC), genistein, chlorophyllin, or
      lycopene were evaluated for their ability to decrease adduct formation of
      [14C]PhIP and [3H]IQ in rats. We also examined the effect of treatments on the
      activity of the phase II detoxification enzymes glutathione S-transferase (GST),
      UDP-glucuronyltransferase (UGT), phenol sulfotransferase (SULT) and quinone
      reductase (QR). PEITC and chlorophyllin significantly decreased PhIP-DNA adduct
      levels in all tissues examined, which was reflected by similar changes in PhIP
      binding to albumin in the blood. In contrast, genistein and lycopene tended to
      increase PhIP adduct levels. The treatments did not significantly alter the level
      of IQ-DNA or -protein adducts in the liver. With the exception of lycopene, the
      treatments had some effect on the activity of one or more hepatic phase II
      detoxification enzymes. We conclude that PEITC and chlorophyllin are protective
      of PhIP-induced genotoxicity after a low exposure dose of carcinogen, possibly
      through modification of HCA metabolism.

PMID- 14690800
TI  - A sociodemographic and neuropsychological characterization of an illiterate
      population.
AB  - The objectives of this article are to characterize the performance and to discuss
      the performance differences between literate and illiterate participants in a
      well-defined study population. We describe the participant-selection procedure
      used to investigate this population. Three groups with similar sociocultural
      backgrounds living in a relatively homogeneous fishing community in southern
      Portugal were characterized in terms of socioeconomic and sociocultural
      background variables and compared on a simple neuropsychological test battery;
      specifically, a literate group with more than 4 years of education (n = 9), a
      literate group with 4 years of education (n = 26), and an illiterate group (n =
      31) were included in this study. We compare and discuss our results with other
      similar studies on the effects of literacy and illiteracy. The results indicate
      that naming and identification of real objects, verbal fluency using ecologically
      relevant semantic criteria, verbal memory, and orientation are not affected by
      literacy or level of formal education. In contrast, verbal working memory
      assessed with digit span, verbal abstraction, long-term semantic memory, and
      calculation (i.e., multiplication) are significantly affected by the level of
      literacy. We indicate that it is possible, with proper participant-selection
      procedures, to exclude general cognitive impairment and to control important
      sociocultural factors that potentially could introduce bias when studying the
      specific effects of literacy and level of formal education on cognitive brain
      function.

PMID- 14690799
TI  - Composition, efficacy, and safety of spinach extracts.
AB  - Spinach leaves, containing several active components, including flavonoids,
      exhibit antioxidative, antiproliferative, and antiinflammatory properties in
      biological systems. Spinach extracts have been demonstrated to exert numerous
      beneficial effects, such as chemo- and central nervous system protection and
      anticancer and antiaging functions. In this review article, we present a
      compilation of data generated in our laboratories and those of other
      investigators describing the chemical composition of spinach, its beneficial
      effects, relative safety information, and its recommended inclusion in the human
      diet. A powerful, water-soluble, natural antioxidant mixture (NAO), which
      specifically inhibits the lipoxygenase enzyme, was isolated from spinach leaves.
      The antioxidative activity of NAO has been compared to that of other known
      antioxidants and found to be superior in vitro and in vivo to that of green tea,
      N-acetylcysteine (NAC), butylated hydroxytoluene (BHT), and vitamin E. NAO has
      been tested for safety and is well tolerated in several species, such as mouse,
      rat, and rabbit. NAO has been found to be nonmutagenic and has shown promising
      anticarcinogenic effects in a few experimental models, such as skin and prostate
      cancer; it has not shown any target-organ toxicity or side effects. The current
      review provides epidemiological and preclinical data supporting the efficacy of
      extracts of spinach and the safety of its consumption.

PMID- 14690801
TI  - Progressive agraphia, acalculia, and anomia: a single case report.
AB  - A case of a 50-year-old, right-handed female, mono-lingual native Spanish-speaker
      with a university-level education and cognitive changes is reported. Over
      approximately 2 years, she presented with a progressive deterioration of writing
      abilities associated with acalculia and anomia. An MRI disclosed a left parietal
      temporal atrophy. Two years later, further significant cognitive decline
      consistent with a dementia of the Alzheimer's type was observed. Amnesia,
      executive dysfunction, and ideomotor apraxia were found. Writing was severely
      impaired, and some difficulties in reading were observed. Copying abilities,
      however, were relatively well preserved, and the patient could drive and go to
      different city locations without significant spatial orientation difficulties. A
      second MRI approximately 2 years later showed that brain atrophy had progressed
      significantly. Spontaneous writing and writing to dictation were impossible. The
      ability to read words was preserved, but the ability to read pseudowords was
      lost. Changes in calligraphy were noted. This case clearly illustrates the
      progression of focal cognitive defects over time and the spread of abnormalities
      to other domains.

PMID- 14690802
TI  - Results of a randomized placebo-controlled study of memory training for mildly
      impaired Alzheimer's disease patients.
AB  - The efficacy of a memory-training program to improve word-list recall and
      recognition was evaluated in 34 patients with probable Alzheimer's disease (AD).
      The patients, who were all taking donepezil throughout the 6-week intervention,
      were randomly assigned to a cognitive intervention group or a control group. The
      Control group received didactic presentations but no formal memory training.
      Patients were assessed on neuropsychological tests before the 6-week training
      program, immediately after the training, and 8 weeks after completion of the
      training. Caregivers, who were blind to group assignment, completed activities of
      daily living (ADLs) and everyday memory questionnaires at all three time-points.
      No significant main effects of group (training vs. control) or time were observed
      on any outcome measures, nor were any significant interactions found. In terms of
      "process" measures during the 6-week training program, the patients demonstrated
      modest improvement on recall and recognition of test material presented during
      the training sessions. These results suggest that although modest gains in
      learning and memory may be evident in AD patients who are taught specific
      strategies, the benefits do not generalize to other measures of
      neuropsychological functioning after a brief intervention.

PMID- 14690803
TI  - Naming multiple objects: neural correlates as measured by positron emission
      tomography.
AB  - The aim of this study was to examine the neural substrates of multi-object naming
      by positron emission tomography in normals. Multi-object naming is used in a
      technique called contextual priming (CP) to elicit contextual effects on picture
      naming through systematic manipulation of the relatedness of to-be-named pictures
      in an array. Inhibitory and facilitatory effects of CP on naming have been used
      both to highlight the inner dynamics of the normal word retrieval system and to
      treat naming difficulties caused by acquired anomia. Because of the complexity of
      the CP technique, it is unclear whether it merely reflects lexical retrieval or
      whether it also recruits general cognitive resources such as attentional control
      and response selection to a significant degree. When compared with a baseline
      situation in which colored circles were named, multi-object naming elicited
      increased blood flow in the occipital lobe and in the left inferior temporal and
      fusiform gyri. These areas have been related to visual pattern recognition and
      semantic access, and the pattern of activation is in line with previous
      functional imaging studies on single picture naming. In conclusion, multi-object
      naming does not appear to activate brain regions beyond those needed for single
      object naming. These findings thus provide independent evidence for the claim
      that CP is a valid paradigm for the study of word production proper.

PMID- 14690804
TI  - Gambling as an executive function task.
AB  - The Iowa Gambling Task (IGT; Bechara, Damasio, Damasio, & Anderson, 1994) was
      investigated in relation to fluid intelligence and two conventional executive
      function tasks: letter fluency and the Wisconsin Card Sorting Test. Fifty-one
      children aged 8-10 years and a heterogeneous group of 40 adults served as
      participants. Adults outperformed children on all measures except one; this was
      the number of good cards selected in the IGT. Intercorrelations among executive
      function tasks were low. The number of good cards in the IGT appeared to be lower
      than in previous studies. Reasons for poor performance are discussed. The IGT may
      possess some shortcomings, which should be investigated in future studies. In
      clinical usage, the IGT may best serve as a complementary tool to the executive
      functions test battery.

PMID- 14690805
TI  - The effect of aging on script memory for typical and atypical actions.
AB  - When typical and atypical information about a situation are presented, the
      atypical is found to be better recognized. This phenomenon is referred to as the
      "typicality effect." To test whether the typicality effect is age related, 41
      younger and 36 older participants listened to two scripts that consisted of
      typical and atypical activities. The recognition was scored in two ways-with and
      without taking confidence rating into account. The two scoring systems yielded a
      similar pattern of results. Nevertheless, the weighted scores analyses were more
      sensitive to group differences than the unweighted scores. The older adults
      demonstrated typicality effect with the false alarm and hit rates corrected for
      false alarms scores but not with the hit rate score. A key factor in
      understanding the effect of age on the typicality effect is taking into
      consideration the conservative response bias found in the older group. The
      clinical contribution of these findings, in terms of assessment and remediation
      of age-related memory impairment, is discussed.

PMID- 14690806
TI  - Comparability of the standard WCST and WCST-64 in traumatic brain injury.
AB  - The aim of this study was to investigate the comparability of the Wisconsin Card
      Sorting Test short form (WCST-64) to the standard form in a clinical population
      with documented brain pathology: chronic severe traumatic brain injury (TBI).
      Participants were 61 patients at least 1 year after severe TBI living at a large
      residential rehabilitation facility. The WCST was administered in standard
      fashion with both the standard and 64-card versions scored. All derived scores
      with norms were examined. Results indicated that the WCST-64 scores were
      comparable to the standard version, and assigned impairment levels remained
      relatively stable. These results suggest the WCST-64 is a valid alternative to
      the standard version in chronic severe TBI.

PMID- 14690807
TI  - Exploratory factor analysis of the Wechsler Abbreviated Scale of Intelligence
      (WASI) in adult standardization and clinical samples.
AB  - Exploratory factor analyses were conducted separately on the Wechsler Abbreviated
      Scale of Intelligence (WASI; The Psychological Corporation, 1999) adult
      standardization sample (n = 1,145) and a diagnostically heterogeneous adult
      clinical sample (n = 201). In the latter group, means for age, education, and
      WASI Full Scale IQ were 59.25 years (SD = 17.52), 12.39 years (SD = 2.88), and
      89.91 (SD = 16.00). For each sample, the four WASI subtests were subjected to a
      principal-axis factor analysis followed by varimax and promax rotations. Two
      factors were specified to be retained. Verbal Comprehension and Perceptual
      Organization factors were identified in both analyses. Coefficients of congruence
      were 0.98 for Factor I and 0.99 for Factor II, suggesting factorial equivalence
      across the standardization and clinical samples.

PMID- 14690848
TI  - Within-compound associations in retrospective revaluation and in direct learning:
      a challenge for comparator theory.
AB  - In three human causal learning experiments we investigated the role of within
      compound associations in learning about absent cues versus learning about present
      cues. Different theoretical approaches agree that within-compound associations
      are essential for learning about absent cues-that is, for retrospective
      revaluation. They differ, however, with regard to the role of within-compound
      associations for learning about present cues-that is, for direct learning. A
      memory test was used to assess within-compound associations. Experiment 1 used a
      blocking/release from overshadowing design, Experiment 2 used a conditioned
      inhibition design, and Experiment 3 used a higher-order cue selection design. In
      all experiments, first-order retrospective revaluation was significantly
      correlated with within-compound associations, but no significant correlations
      were found for the direct learning conditions. In addition to this, second-order
      retrospective revaluation in Experiment 3 was positively correlated to joint
      knowledge of first-order and second-order within-compound associations.
      Furthermore, cue selection effects were stronger for direct learning conditions
      than for retrospective learning conditions. These results are at variance with
      the comparator hypothesis but are in agreement with a modified associative theory
      and with the suggestion that retrospective revaluation might be due to rehearsal
      processes.

PMID- 14690847
TI  - Comparing excitatory backward and forward conditioning.
AB  - Three Pavlovian lick suppression studies with rats were conducted to compare the
      role of the conditioning context in excitatory backward and forward conditioning.
      The experiments explored the possibility that excitatory backward conditioning,
      but not forward conditioning, is mediated by the context. That is, in excitatory
      backward conditioning, the conditioning context may function as an excitatory
      mediator, which supports second-order conditioning of the target cue. This
      possibility contrasts with traditional accounts, which suggests that common
      processes underlie excitatory backward and forward conditioning. Experiment 1
      found that conditioned responding following backward conditioning was attenuated
      as a result of posttraining extinction of the training context, but the same
      manipulation elevated responding after forward conditioning. Experiments 2 and 3
      found that posttraining and pretraining associative inflation of the context
      (presenting unsignalled USs) increased conditioned responding to the target of a
      backward conditioning procedure but either had no effect or reduced responding to
      the target of a forward conditioning procedure. Thus, excitatory backward and
      forward conditioning appear to differ in their dependence on the status of the
      conditioning context.

PMID- 14690849
TI  - Double standards: memory loading in temporal reference memory.
AB  - Three experiments compared human performance on temporal generalization tasks
      with either one or two different, and distinct, standard durations encoded. In
      the first two experiments participants received presentations of two different
      standards at the beginning of each trial block and were instructed to encode
      either one or both of them. When instructed to encode one standard they then had
      to judge whether each of a number of comparison stimuli was or was not that
      standard. When instructed to encode both they were then tested using just one of
      the standards but the participants were unaware, at the time of encoding, which
      standard would later be used as a reference. No marked effect of the number of
      temporal standards encoded was found. In Experiment 3 participants received
      either one or two temporal standards and had to use both when two were presented.
      This manipulation produced flatter generalization gradients when two standards
      were encoded than when just one was, and modelling attributed this difference
      mainly to an increase in reference memory variability in the double-standard
      case. This suggests that the variability of representation of durations in
      temporal reference memory can be systematically increased by increasing temporal
      reference memory load.

PMID- 14690850
TI  - Brief communication: the role of category structure in determining the effects of
      stimulus preexposure on categorization accuracy.
AB  - What are the effects of preexposure of stimuli on participants' subsequent
      ability to categorize them accurately? An experiment employing artificial,
      abstract, visual stimuli confirms that, for adult humans, the effect of
      preexposure is dependent upon category structure. Whether preexposure has
      beneficial or detrimental effects is shown to be dependent on the way category
      examples are generated from the category base patterns. The results are predicted
      by salience reduction accounts of perceptual learning but may be problematic for
      stimulus differentiation accounts.

PMID- 14690852
TI  - Virus infection and apoptosis (issue II) an introduction: cheating death or death
      as a fact of life?
AB  - Apoptosis represents the cell's innate ability to self-destruct and is an
      important cellular response mechanism against virus infection. The purpose of
      this series of articles is to critically review significant advances in important
      areas of virology with respect to virus infection and its relationship with
      apoptosis. In the Introduction to the first issue (Intern. Rev. Imm., 22: 321
      326, 2003), we dedicated these entire two issues to the memory of Dr. Lois K.
      Miller. Dr. Miller's Ph.D. advisor, Robert D. Wells, and two of her students,
      Rollie Clem and Lorena Passarelli, contributed touching remembrances of their
      associations with Dr. Miller. In the Introduction to this issue, an overview of
      key points of discussion detailed in each chapter of the two issues is provided.
      The future of the emerging field of viral apoptosis remains bright, indeed.

PMID- 14690853
TI  - Alphaviruses and apoptosis.
AB  - Many reports have indicated that infection with SV or SFV induces apoptosis both
      in cultured cells and in the CNS of mice. In general, the ability of virus
      strains to induce apoptosis correlates with their neurovirulence, although both
      apoptosis and neurovirulence are age dependent, i.e., resistance increases with
      age. SV can induce apoptosis simply by the process of membrane fusion and entry,
      by the expression of the envelope proteins, or by the expression of the
      nonstructural protein, nsP2. However, viral particles are not necessary to
      activate apoptosis, since transfection with viral RNA or even viral RNA
      expressing only the nonstructural proteins will result in apoptosis. The cellular
      pathways involved in alphavirus-induced apoptosis are complex, and much remains
      poorly understood. Experimental results point to the involvement of both the
      mitochondrial and the death receptor pathways. To date, there are no reports
      implicating the ER stress pathway.

PMID- 14690854
TI  - T-cell and neuronal apoptosis in HIV infection: implications for therapeutic
      intervention.
AB  - The pathogenesis of HIV infection involves the selective loss of CD4+ T cells
      contributing to immune deficiency. Although loss of T cells leading to immune
      dysfunction in HIV infection is mediated in part by viral infection, there is a
      much larger effect on noninfected T cells undergoing apoptosis in response to
      activation stimuli. In the subset of patients with HIV dementia complex, neuronal
      injury, loss, and apoptosis are observed. Viral proteins, gp120 and Tat, exhibit
      proapoptotic activities when applied to T cell and neuronal cultures by direct
      and indirect mechanisms. The pathways leading to cell death involve the
      activation of one or more death receptor pathways (i.e., TNF-alpha, Fas, and
      TRAIL receptors), chemokine receptor signaling, cytokine dysregulation, caspase
      activation, calcium mobilization, and loss of mitochondrial membrane potential.
      In this review, the mechanisms involved in T-cell and neuronal apoptosis, as well
      as antiapoptotic pathways potentially amenable to therapeutic application, are
      discussed.

PMID- 14690855
TI  - Poxvirus infection and apoptosis.
AB  - The following excellent reviews have been published on poxviruses and apoptosis
      during the last few years: P.C. Turner and R.W. Moyer, Semin. Virology, 8: 453
      469, 1998; J.L. Shisler and B. Moss, Semin. Immunol., 13: 67-72, 2001; and H.
      Everett and G. McFadden, Curr. Opin. Microbiol., 5: 395-402, 2002. These articles
      dealt with the viral products and the mechanisms by which they interfere with
      apoptosis. In this review, we summarize new and old information and also
      introduce a new approach to explore interactions between the host cell and the
      replicating virus.

PMID- 14690856
TI  - Functions and mechanisms of action of the adenovirus E3 proteins.
AB  - In the evolutionary battle between viruses and their hosts, viruses have armed
      themselves with weapons to defeat the host's attacks on infected cells. Various
      proteins encoded in the adenovirus (Ad) E3 transcription unit protect cells from
      killing mediated by cytotoxic T cells and death-inducing cytokines such as tumor
      necrosis factor (TNF), Fas ligand, and TNF-related apoptosis-inducing ligand
      (TRAIL). The viral protein E3-gp19 K blocks MHC class-I-restricted antigen
      presentation, which diminishes killing by cytotoxic T cells. The receptor
      internalization and degradation (RID) complex (formerly E3-10.4 K/14.5 K)
      stimulates the clearance from the cell surface and subsequent degradation of the
      receptors for Fas ligand and TRAIL, thereby preventing the action of these
      important immune mediators. RID also downmodulates the epidermal growth factor
      receptor (EGFR), although what role, if any, this function has in immune
      regulation is uncertain. In addition, RID antagonizes TNF-mediated apoptosis and
      inflammation through a mechanism that does not primarily involve receptor
      downregulation. E3-6.7 K functions together with RID in downregulating some TRAIL
      receptors and may block apoptosis independently of other E3 proteins.
      Furthermore, E3-14.7 K functions as a general inhibitor of TNF-mediated apoptosis
      and blocks TRAIL-induced apoptosis. Finally, after expending great effort to
      maintain cell viability during the early part of the virus replication cycle, Ads
      lyse the cell to allow efficient virus release and dissemination. To perform this
      task subgroup C Ads synthesize a protein late in infection named ADP (formerly E3
      11.6 K) that is required for efficient virus release. This review focuses on
      recent experiments aimed at discovering the mechanism of action of these
      critically important viral proteins.

PMID- 14690857
TI  - HCMV infection: modulating the cell cycle and cell death.
AB  - Human cytomegalovirus (HCMV) is a member of the Herpesviridae family and is
      recognized as a significant pathogen to certain subgroups of the human
      population. It has become apparent that HCMV manipulation of the host cell cycle
      as well as the immune response promotes the replication and propagation of the
      virus. The ability of HCMV to modulate components of the host immune system and
      the response to infection most likely contributes to the pathology associated
      with this virus. This review will address the mechanisms HCMV has adapted to
      modulate the cell cycle to promote viral replication as well as the different
      ways it can prevent the "death" of an infected cell.

PMID- 14690858
TI  - Herpes simplex virus infection and apoptosis.
AB  - Consequences of human herpes simplex virus (HSV) infection include the induction
      of apoptosis and the concomitant synthesis of proteins which act to block this
      process from killing the infected cell. Recent data has clarified our current
      understanding of the mechanisms of induction and prevention of apoptosis by HSV.
      These findings emphasize the fact that modulation of apoptosis by HSV during
      infection is a multicomponent phenomenon. We review recent evidence showing how
      this important human pathogen modulates the fundamental cell death process.

PMID- 14690859
TI  - A role for apoptosis induced by acute herpes simplex virus infection in mice.
AB  - Acute herpes simplex virus (HSV) infection causes apoptosis in the adrenal cortex
      and myenteric plexus of the gut, ovary, pituitary gland, and liver of mice.
      Apoptosis of infected cells is increased in immunosuppressed regions of the
      adrenal cortex and liver of macrophage-depleted mice. HSV carries the US3 gene
      which interferes with host cell apoptosis. When the livers of macrophage-depleted
      mice are infected with a US3-null virus, apoptosis occurs in the narrow areas of
      inflammatory cell infiltration, restricting viral replication and spread. Thus,
      these data suggest that apoptosis may function as a primitive immune response to
      HSV infection in mice.

PMID- 14690860
TI  - HSV LAT and neuronal survival.
AB  - Herpes Simplex Virus (HSV) establishes a latent infection within sensory neurons
      and periodically reactivates in response to stress. HSV's ability to inhabit
      neurons for the life of the host involves a number of virally encoded functions
      that tightly regulate the latency-reactivation cycle, preventing uncontrolled
      spread of reactivating virus and large-scale death of neurons. The HSV latency
      associated transcript (LAT) is a complex transcription unit expressed primarily
      in neurons containing latent genomes. While mutational analyses indicate LAT is
      nonessential for viral replication, the 5' exon of LAT greatly enhances
      reactivation. Several studies have also identified LAT mutations that reduce
      establishment of latency and enhance virulence. Recently, LAT has also been shown
      to inhibit cell death through by blocking caspase-8 and caspase-9 pathways. While
      blocking apoptosis is not essential for either establishment of latency or
      reactivation, it likely augments these processes and may contribute to HSV's long
      term persistence and spread.

PMID- 14690861
TI  - Neutralizing innate host defenses to control viral translation in HSV-1 infected
      cells.
AB  - Lytic replication of many viruses activates an innate host response designed to
      prevent the completion of the viral lifecycle, thus impeding the spread of the
      infection. One branch of the host's complex reaction functions to incapacitate
      the cellular translational machinery on which the synthesis of viral polypeptides
      completely depends. This is achieved through the activation of specific protein
      kinases that phosphorylate eIF2 on its alpha subunit and inactivate this critical
      translation initiation factor. However, as continued synthesis of viral proteins
      is required to assemble the viral progeny necessary to transmit the infection to
      neighboring cells, viruses have developed a variety of strategies to counter this
      cellular response. Genetic and biochemical studies with herpes simplex virus type
      1 (HSV-1) have revealed that the virus produces at least two discrete products at
      different times during its replicative program that act to prevent the
      accumulation of phosphorylated eIF2alpha. The gamma(1)34.5 gene product is
      expressed first, encoding a regulatory subunit that binds the cellular protein
      phosphatase 1alpha and regenerates pools of active eIF2 by removing the
      inhibitory phosphate from the alpha subunit. The second function, encoded by the
      product of the Us11 gene, specifies a double-stranded RNA-binding protein that
      prevents activation of PKR, a cellular eIF2alpha kinase. Together, both proteins
      cooperate to overcome the antiviral response of the host and properly regulate
      translation in HSV-1-infected cells.

PMID- 14690862
TI  - Music interventions for people with dementia: a review of the literature.
AB  - This paper provides a qualitative review of 21 published articles of clinical
      empirical studies looking at the effects of a variety of music activities on the
      emotional and behavioural responses in people with dementia. General information
      is reviewed such as the setting and context of studies, research findings and
      explanatory variables. Methodological issues are also discussed, particularly in
      relation to observational methods, and theoretical frameworks such as the
      progressively lowered stress threshold model are evaluated. Music appears to have
      a range of applications in dementia care but previous reviews have highlighted
      methodological weaknesses of studies. Recommendations for future research include
      the use of continuous time sampling methodology and to record the duration of
      observed behaviours. This review paper also argues for the use of Kitwood's
      theory of personhood as a framework to inform and guide future research.

PMID- 14690863
TI  - What factors influence mental health professionals when deciding whether or not
      to share a diagnosis of dementia with the person?
AB  - This study investigated what influences mental health professionals when deciding
      whether or not to tell someone with dementia their diagnosis. A qualitative
      methodology was employed and the data analysed using grounded theory. Currently
      people with dementia tend not to be told their diagnosis, despite evidence that
      sharing diagnostic information can improve psychological well-being and
      adjustment. Why professionals are reluctant to share diagnostic information with
      people with dementia is unclear, although the literature raises a number of
      possibilities. Seven professionals were interviewed (two clinical psychologists
      and five community psychiatric nurses). The main influence on their disclosure
      practice was uncertainty about whether the person with dementia would want to
      know the diagnosis, fueled by a fear that to tell them if they did not want to
      know would cause harm. Professionals also expressed a strong sense of both
      hopelessness and helplessness when confronted with dementia. This was then
      projected onto the person with dementia, which in turn led to the professionals
      adopting an overly protective stance towards them. If professionals are to
      resolve their sense of uncertainty about what the person with dementia wants, in
      terms of diagnostic information, services need to develop ways in which the views
      of people with dementia can be heard and start to influence service provision and
      policy.

PMID- 14690864
TI  - Self-efficacy, health locus of control, and psychological distress in elderly
      Chinese women with chronic illnesses.
AB  - This study examined the associations among self-efficacy, health locus of
      control, and psychological distress in 159 elderly Chinese women who had chronic
      physical illnesses. The present findings did not support the dual health control
      hypothesis that specifies the balance between internal and external health
      control beliefs is related to a low level of psychological distress. Correlation
      results showed that internal health locus of control was linked to general self
      efficacy. Results from hierarchical regression analysis indicated that health
      control beliefs did not interact with general self-efficacy; instead, these two
      variables each exerted their main effects on participants' negative mental health
      status. It was found that psychological distress was best predicted by a low
      level of general self-efficacy as well as a high level of external health locus
      of control. Internal health control beliefs did not contribute to the prediction
      of distress. Implications and limitations of this study were also discussed.

PMID- 14690865
TI  - The relationship between self-destructive behaviour and nursing home environment.
AB  - The aim of this study was to explore the relationship between self-destructive
      behaviour and nursing home environment. We performed a cross-sectional study
      comprising 647 residents in 11 nursing homes in Sydney, Australia using the
      Harmful Behaviours Scale (HBS), Abbreviated Mental Test Scale and the Resident
      Classification Index. The Directors of Nursing completed a questionnaire that
      rated physical design, staff and resident characteristics and demographics were
      obtained from nursing home records. On regression analysis a greater number of
      design features for frail and residents with dementia in general, and increased
      security measures were associated with greater HBS total score and risk-taking
      and passive self-harm subscales. A residential environment in which the residents
      were more functionally dependent and more likely to be in a shared room,
      managerial policies less geared towards managing difficult behaviour and less
      staff availability and training were associated with the 'uncooperativeness'
      factor. There were no significant predictors of the other two factors. The
      relationship between nursing home environment and self-destructive behaviours and
      the environment is complex and there needs to be an individualized approach to
      placement.

PMID- 14690866
TI  - Delayed discharge--a solvable problem? The place of intermediate care in mental
      health care of older people.
AB  - The National Service Framework for Older People envisages the development of
      intermediate care for older people. This study examined the possible role of
      intermediate care beds within mental health trusts. We interviewed senior
      clinicians in an inner city old age psychiatry service about the 91 current in
      patients on the old age psychiatric wards. Sixty-five were classified as acute
      patients and the remaining 26 were continuing care patients. Structured
      instruments were used to collect information regarding neuropsychiatric symptoms,
      activities of daily living and current met and unmet needs. Where discharge was
      delayed an assessment was made regarding the appropriateness for an intermediate
      care setting according to the criteria set by the Department of Health
      guidelines. A total of 30 (46%) patients' discharges were delayed. Of these, 19
      (29%) patients met the DOH criteria for intermediate care; 10 (53%) had dementia,
      five (26%) affective disorder, and four (21%) with schizophrenia. The 11 other
      delayed discharges were because of lack of availability of finance for
      placements. The study found that the prompt discharge of older patients from
      acute psychiatric care was a significant problem and many of those patients may
      benefit from the therapeutic and rehabilitative process afforded by intermediate
      care.

PMID- 14690867
TI  - Outcomes for patients with dementia from the Cleveland Alzheimer's Managed Care
      Demonstration.
AB  - This investigation evaluates effects of care consultation delivered within a
      partnership between a managed health care system and Alzheimer's Association
      chapter. Care consultation is a multi-component telephone intervention in which
      Association staff work with patients and caregivers to identify personal
      strengths and resources within the family, health plan, and community. The
      primary hypothesis is that care consultation will decrease utilization of managed
      care services and improve psychosocial outcomes. A secondary modifying-effects
      hypothesis posits benefits will be greater for patients with more severe memory
      impairment. The sample is composed of managed care patients whose medical records
      indicate a diagnosis of dementia or memory loss. Patients were randomly assigned
      to an intervention group, which was offered care consultation in addition to
      usual managed care services, or to a control group, which was offered only usual
      managed care services. Data come from two in-person interviews with patients, and
      medical and administrative records. Results supporting the primary hypothesis
      show intervention group patients feel less embarrassed and isolated because of
      their memory problems and report less difficulty coping. Findings consistent with
      the modifying-effects hypothesis show intervention group patients with more
      severe impairment have fewer physician visits, are less likely to have an
      emergency department visit or hospital admission, are more satisfied with managed
      care services, and have decreased depression and strain.

PMID- 14690868
TI  - The diagnostic value of IADL evaluation in the detection of dementia in general
      practice.
AB  - It is assumed that general practitioners can make an important contribution to
      the diagnosis of dementia. One of the used strategies comprises an evaluation of
      the Instrumental Activities of Daily Living (IADL). There are contradictory data
      on the value of this strategy. During one month, 21 Flemish general practitioners
      evaluated the IADL capacities of all subjects older than 65 years with whom they
      had contact. Subjects with dementia and/or living in a residential home for the
      elderly were excluded. Housing and living conditions, medication use and IADL
      were registered. The general practitioner formulated a clinical evaluation. All
      subjects with an IADL score > or = 1 and a random sample from the group IADL = 0
      underwent a Mini Mental State Examination. Subjects with an IADL score = 4 were
      referred for neuropsychological and specialist examination. The average age of
      the 1003 registered subjects was 75.1 years (SD = 6.8). A large majority of them
      (85%) were totally independent. There was a large discrepancy between the
      family's and the patient's judgment on the presence of memory problems. There was
      an inverse correlation between the IADL and MMSE: when the IADL score increased,
      the MMSE score fell. The diagnostic value of the IADL for the diagnosis of
      dementia with Camdex-N as a reference standard could not be evaluated because the
      number of tested subjects was too small. Against the MMSE, sensitivity was 0.81
      (SE = 0.03), and specificity was 0.48 (SE = 0.05). The evaluation of the IADL
      activities had some drawbacks as a detection method for dementia but the use of
      IADL data may still be clinically valuable in general practice. The correlation
      between the general practitioner's judgment and that of the specialist was very
      good. This study showed that the use of the IADL score might change the general
      practitioner's diagnostic judgment. Furthermore this study confirms the existence
      of a major threshold for the referral to a specialist of patients with suspected
      dementia by general practitioners.

PMID- 14690869
TI  - Positive illusions and mental and physical health in later life.
AB  - There are three competing conceptions concerning the relationship between
      positive illusions and mental health: the 'traditional' mental health model,
      according to which an accurate perception of the self and the world is a
      cornerstone of psychological well-adjustment; Taylor and Brown's Social
      Psychological Model on mental health, which assumes that positive illusions
      promote good mental health; and Baumeister's Optimal Margin Theory, which states
      that too much accuracy is harmful to mental health, as are exaggerated illusions.
      These three models were evaluated in the elderly (n = 857 retirees ages 60-95)
      using the youthful bias, which is the illusion of being younger than one's real
      age. As a whole, the Social Psychological Model obtained the strongest support.
      Retirees who harboured an exaggerated youthful bias (more than 15 years) reported
      more satisfaction with leisure time, higher self-esteem, better perceived health,
      and less boredom proneness than those who felt as old as they were or who, except
      for perceived health, entertained a moderate youthful bias (between 1 and 15
      years).

PMID- 14690870
TI  - Family involvement in nursing homes: effects on stress and well-being.
AB  - While it is clear that families remain involved in the lives of loved ones
      following placement in a nursing home, little research has examined whether
      visiting and the provision of care has effects on the emotional stress and
      psychological well-being of family members. Utilizing pre-placement and post
      placement data from the Caregiver Stress and Coping Study (n = 185) as well as a
      theoretical framework to delineate the manifestation of caregiver stress (i.e.,
      the stress process model), the goal of this analysis was to determine whether
      frequency of visits and provision of personal and instrumental activities of
      daily living assistance following institutionalization were related to post
      placement emotional distress, family conflict, and psychological well-being among
      family members. Following control of a wide array of pre-placement and post
      placement covariates, multiple regression models found that visiting was
      negatively associated with post-placement role overload; moreover, the provision
      of instrumental activities of daily living help was negatively related to loss of
      intimate exchange at post-placement. The results suggest that family involvement
      following institutionalization may operate differently than when in the
      community, and add to the literature emphasizing the positive implications of
      family involvement in residential long-term care.

PMID- 14690871
TI  - Screening for alcohol abuse and dependence in older people using DSM criteria: a
      review.
AB  - Alcohol abuse and dependence in older people are important problems, which
      frequently remain undetected by health services. Therefore, screening instruments
      for alcohol abuse and dependence in elderly people would be useful in clinical
      practice. To assess the quality of screening instruments we performed a
      literature search in Medline (1966-2002) and PsycINFO (1967-2002). Seven research
      reports were found. The MAST-G and especially the CAGE appear appropriate. The
      two questions of Cyr and Wartman, AUDIT and the MAST do not appear appropriate in
      screening for alcohol abuse and dependence in elderly people in a clinical
      environment.

PMID- 14690872
TI  - Congestive heart failure patients' perceptions of quality of life: the
      integration of physical and psychosocial factors.
AB  - Congestive heart failure (CHF) lowers survival and worsens the quality of life
      (QOL) of over four million older Americans. Both clinicians and standardized
      instruments used to assess the QOL of patients with CHF focus primarily on
      physical symptoms rather than capturing the full range of psychosocial concerns.
      The purpose of this study was to gather descriptions of the components of QOL as
      understood by patients living with CHF. Focus groups were conducted with patients
      with known CHF, New York Heart Association (NYHA) class I-IV, and left
      ventricular fraction of <40%. Focus groups were audiotaped, transcribed, and
      reviewed for common and recurrent themes using the methods of constant
      comparisons. We conducted three focus groups (n = 15) stratified by NYHA stage
      with male patients ranging in age from 47-82 years of age. Five patients were
      classified with NYHA stage III/IV and ten with NYHA stage I/II. Thirty attributes
      of QOL were identified which fell into five broad domains: symptoms, role loss,
      affective response, coping, and social support. Expectedly, patients reported the
      importance of physical symptoms; however, participants also identified concern
      for family, the uncertainty of prognosis, and cognitive function as dimensions of
      QOL. Changes in patients' lives attributed to CHF were not always considered
      deficiencies; rather, methods of coping with CHF were identified as important
      attributes representing possible opportunities for personal growth. Clinicians
      must understand the full range of concerns affecting the QOL of their older
      patients with CHF. The findings suggest that psychosocial aspects and patient
      uncertainty about their prognosis are important components of QOL among CHF
      patients.

PMID- 14690873
TI  - The effect of alcohol consumption on endothelial adhesion molecule expression.
AB  - Endothelial adhesion molecules (AM) play an important role in the pathogenesis of
      several diseases namely infections, neoplasms and chronic inflammatory diseases.
      Because alcoholic hepatitis and even atherosclerosis are considered as
      inflammatory diseases and ethanol may modulate inflammatory response, several
      researchers have investigated the link between ethanol consumption, endothelial
      AM and the development of both processes. In vitro, animal and human studies have
      analysed the effects of ethanol and non-alcoholic components of alcoholic
      beverages on inflammatory biomarkers of atherosclerosis such as monocyte and
      endothelial AM. These studies have shown that both ethanol and non-alcoholic
      components of alcoholic beverages, mainly polyphenols, reduce intercellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E
      selectin expression of vascular endothelium, as well as monocyte adhesion to this
      endothelium. These data suggest that moderate alcohol intake has an anti
      inflammatory effect on the cardiovascular system and reduces early serum markers
      of atherosclerosis. However, at higher doses ethanol may exert an inflammatory
      effect. In fact, chronic alcoholics exhibit significantly higher serum levels of
      endothelial AM than abstainers and moderate drinkers. In addition, an
      upregulation of E-selectin, ICAM-1 and VCAM-1 is also detected in liver biopsies
      obtained from patients with alcoholic hepatitis and cirrhosis. The clinical
      usefulness of the measurement of serum endothelial AM is discussed.

PMID- 14690874
TI  - Drug/substance reversal effects of a novel tri-substituted benzoflavone moiety
      (BZF) isolated from Passiflora incarnata Linn.--a brief perspective.
AB  - The present work is a mini-review of the author's original work on the plant
      Passiflora incarnata Linn., which is used in several parts of the world as a
      traditional medicine for the management of anxiety, insomnia, epilepsy and
      morphine addiction. A tri-substituted benzoflavone moiety (BZF) has been isolated
      from the bioactive methanol extract of this plant, which has been proposed in the
      author's earlier work to be responsible for the biological activities of this
      plant. The BZF moiety has exhibited significantly encouraging results in the
      reversal of tolerance and dependence of several addiction-prone psychotropic
      drugs, including morphine, nicotine, ethanol, diazepam and delta-9
      tetrahydrocannabinol, during earlier pharmacological studies conducted by the
      author. In addition to this, the BZF moiety has exhibited aphrodisiac, libido
      enhancing and virility-enhancing properties in 2-year-old male rats. When
      administered concomitantly with nicotine, ethanol and delta-9
      tetrahydrocannabinol for 30 days in male rats, the BZF also prevented the drug
      induced decline in sexuality in male rats. Because the BZF moiety isolated from
      P. incarnata is a tri-substituted derivative of alpha-naphthoflavone (7,8
      benzoflavone), a well-known aromatase-enzyme inhibitor, the mode of action of BZF
      has been postulated to be a neurosteroidal mechanism vide in which the BZF moiety
      prevents the metabolic degradation of testosterone and upregulates blood -
      testosterone levels in the body. As several flavonoids (e.g. chrysin, apigenin)
      and other phytoconstituents also possess aromatase-inhibiting properties, and the
      IC50 value of such phytomoieties is the main factor determining their biochemical
      efficacy, by altering their chemical structures to attain a desirable IC50 value
      new insights in medical therapeutics can be attained, keeping in view the menace
      of drug abuse worldwide.

PMID- 14690875
TI  - Brain mitochondrial aldehyde dehydrogenase: relation to acetaldehyde aversion in
      low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) rats.
AB  - Previous reports indicate that the low-drinker (UChA) rats, when compared to high
      drinker (UChB) rats, display lower mitochondrial aldehyde dehydrogenase (ALDH2)
      activity due to a mutation of the Aldh2 gene. Because a later study found line
      differences in sensitivity to the aversive effects of acetaldehyde (AcH)
      administered intraperitoneally (i.p.), which were not associated with the line
      difference detected in blood AcH levels, the present study examined the
      contribution of brain ALDH2 activity to AcH aversion in UChA and UChB rats. In
      experiment 1, we established the dose - response curves for AcH aversion (25, 50
      or 100 mg/kg i.p.) in rats of both lines by using a conditioned taste aversion
      (CTA) paradigm. The results confirm our previous finding that UChA and UChB rats
      presented marked differences in their AcH aversion thresholds, which were not
      associated with the line differences detected in blood AcH levels. In experiment
      2, the possibility that the inhibition of the brain ALDH2 would lower the AcH
      aversion threshold in both lines was studied by determining the effect of
      cyanamide (10 mg/kg i.p.) pretreatment, an inhibitor of ALDH, on AcH aversion,
      blood AcH levels and brain ALDH2 activity. The finding that blocking the brain
      ALDH2 (52%) by cyanamide can make a non-aversive dose of AcH (25 mg/kg) aversive
      to UChA and UChB rats at blood AcH levels comparable to those induced by a non
      aversive dose of AcH (100 mg/kg) in control UChB rats indicates that the line
      difference in AcH aversion is associated more with brain ALDH2 activity than with
      liver ALDH2 activity.

PMID- 14690876
TI  - Open field activity and EtOH activation of gamma-PKC null mutants.
AB  - Null mutants of the neural-specific gamma-isotype of protein kinase C (gamma-PKC)
      have demonstrated differential responses to acute administration of ethanol in
      comparison with wild-type animals. Previous studies have shown that the mutants
      are less sensitive to ethanol-induced loss of righting response. Null mutants
      also consume more ethanol and exhibit less behavioral inhibition. In order to
      determine if these sensitivity differences extend to ethanol activation of
      locomotor activity in an open-field arena, baseline activity and the effect of
      two low doses of ethanol were assessed in gamma-PKC null mutants and wild-type
      littermates. Null mutants demonstrated higher levels of baseline activity than
      did their wild-type counterparts. Further analysis revealed that a 1.0 g/kg dose
      of ethanol increased locomotor activity in males and females of both genotypes,
      whereas only null mutant males were activated by a 1.25 g/kg ethanol dose. The
      current study demonstrates that male gamma-PKC null mutants exhibit increased
      sensitivity to activating doses of ethanol in contrast to previous findings of
      decreased sensitivity to higher, depressive doses. This reflects the pleiotropic
      effects of the gamma-PKC null mutation on the behavioral effects of ethanol.

PMID- 14690877
TI  - P-glycoprotein modulation by the designer drugs methylenedioxymethamphetamine,
      methylenedioxyethylamphetamine and paramethoxyamphetamine.
AB  - There are increasing numbers of deaths related to taking MDMA, MDE and PMA
      reported where the deceased typically took several different drugs with these
      compounds. Hence, mutual modulation of the pharmacokinetics in drug combinations
      with "ecstasy" might be a risk factor for "ecstasy"-related morbidity. Regarding
      potential drug - drug interactions, there are no data evaluating a possible
      contribution of the multidrug resistance transporter P-glycoprotein (Pgp) in
      contrast to the cytochrome P450 enzyme system. Therefore, individual "ecstasy"
      compounds have been tested for their ability to interact with Pgp using a
      fluorometric calcein assay as a model for Pgp inhibition in porcine kidney
      epithelial cells with overexpression of human Pgp (L-MDR1). All three compounds
      increased calcein retention in L-MDR1 cells in a concentration-dependent manner,
      with MDE being the most potent and MDMA the weakest Pgp inhibitor. The effective
      concentrations were 1 - 3 orders of magnitude higher than plasma concentrations
      observed in vivo, suggesting that these compounds are only weak inhibitors of
      Pgp, which is unlikely to influence the access of other compounds to the brain.
      However, it cannot be excluded that co-administration of Pgp inhibitors such as
      ritonavir or paroxetine could increase MDMA, MDE and PMA bioavailability and also
      enhance brain entry leading to severe side effects.

PMID- 14690878
TI  - Age- and sex-related differences in alcohol and nicotine effects in C57BL/6J
      mice.
AB  - The present studies were aimed to identify possible age- and/or sex-related
      differences in the effects of alcohol and nicotine. Study 1 examined age-related
      differences in alcohol and nicotine effects. Adolescent and adult C57BL/6J male
      mice were injected with alcohol or nicotine. Results indicated that alcohol and
      nicotine induced hypothermia and reduced locomotor activity in both adolescent
      and adult mice. In both dependent variables, adults were more affected than
      adolescents that received the same alcohol or nicotine dose. Study 2 examined
      possible sex-related differences in the effects of these drugs. Results
      replicated the aged-related differences revealed in Study 1 after alcohol or
      nicotine administration in male mice. No sex-related differences were observed in
      alcohol effects. However, young animals of both sexes and adult females appeared
      to be more resistant to nicotine effects. In both studies, blood alcohol
      concentrations and cotinine plasma concentrations were assessed. These results
      suggest that young C57BL/6J mice are more resistant to both alcohol and nicotine
      effects. In addition, adult females may be more resistant to acute nicotine
      effects on temperature and locomotion.

PMID- 14690879
TI  - Maintenance treatment with depot opioid antagonists in subcutaneous implants: an
      alternative in the treatment of opioid dependence.
AB  - A report is presented of treatment of 156 patients (male 98%) with opioid
      dependence (ICD-10 criteria) using a maintenance programme with depot opioid
      antagonists (naltrexone) as subcutaneous implants, started after an outpatient
      rapid antagonization regimen. The retention index in the treatment was from 80%
      in the sixth month, and 65% after one year. The patients were followed-up for 1
      year after discharge. For 6 months after discharge 55.4% were still returning for
      follow-up visits and 20.8% after 1 year, all of them remaining abstinent to
      opioids. It is concluded that the programme is safe for the patients and shows a
      better retention index than programmes using oral antagonists, with an improved
      compliance (negative urine analysis) compared to the latter.

PMID- 14690880
TI  - An audit of the effectiveness of amphetamine isomer ratios as a marker of
      Dexedrine compliance in amphetamine abusers.
AB  - The effectiveness of using amphetamine isomer ratios to determine individual
      compliance with a Dexedrine (dexamphetamine, Celltech, Slough, UK) treatment
      regimen for the maintenance and detoxification from amphetamine abuse has been
      audited. The calculation of l/d-amphetamine isomer ratios in urine has been shown
      previously to provide an accurate method for determining the compliance of
      subjects prescribed dexamphetamine. This audit was performed on the results
      obtained subsequent to the analysis of 369 urine specimens collected from 87
      subjects (26 female, 61 male), all prescribed dexamphetamine collected from
      January 1999 to December 2002. The analysis was performed using a chiral
      derivatizing agent in conjunction with a gas chromatograph fitted with a mass
      spectrometer. It was found that only 245 specimens (66%) were deemed to be from
      compliant subjects. Of the remainder, 60 (16%) were collected when subjects were
      apparently supplementing their dexamphetamine prescription with illicit
      amphetamine, and 66 (18%) were collected when subjects were apparently using
      primarily illicit amphetamine. In summary, a sensitive and specific technique has
      been developed and applied to the analysis of urine specimens obtained from those
      prescribed dexamphetamine to facilitate the monitoring of their compliance. It is
      hoped that this technique may continue to be used to audit further the treatment
      in these individuals in the future to optimize their management.

PMID- 14690881
TI  - Alcohol beverages and biochemical changes in blood.
AB  - Coronary atherosclerosis is the major cause of death in western civilization: one
      of every three in men as well as in women. It was shown that diets supplemented
      with moderate quantities of alcoholic beverages could lead to positive
      biochemical changes in blood of the consumers, which are regarded widely as
      indicators of improved prevention of atherosclerosis. This review summarizes the
      recent epidemiological, experimental and clinical investigations concerning
      mainly the plasma biochemical changes in lipid levels, anticoagulant and
      antioxidant activities.

PMID- 14690882
TI  - Sequential studies of sleep disturbance and quality of life in abstaining
      alcoholics.
AB  - Previous studies in recently detoxified dependent alcoholics have shown severely
      disturbed sleep and impaired quality of life. Although this association has been
      found to predict short-term relapse to heavy drinking, no sequential studies have
      been conducted to monitor significant changes in sleep quality and quality of
      life in abstaining alcoholics. Fifty-seven inpatients at a voluntary sector 12
      Step alcohol detoxification unit in South London were administered a series of
      questionnaires assessing sleep (Pittsburgh Sleep Quality Index, PSQI), Quality of
      Life (Euro-Qol) and Depression and Anxiety (Hospital Anxiety and Depression
      Scales, HADS). Questionnaires were administered at baseline and for 12 weeks at
      monthly intervals. At baseline, PSQI scores showed that 52 of the 57 participants
      suffered from impaired sleep. The scores, however, did not correlate
      significantly with any of the other measurements. All except two participants
      acknowledged impaired Quality of Life in at least one area. With respect to the
      follow-up measurements 23 (40%) participants completed the study. Quality of life
      and depression scores improved significantly over a 12-week period but sleep and
      anxiety scores did not. At 12 weeks the mean PSQI score was still above the cut
      off point for 'sleep caseness'. Quality of life and depression show a significant
      improvement over a 3-month period of abstinence, although at this point the
      subjects are still experiencing difficulties with sleep and anxiety. This
      information could help in the planning of future rehabilitation and treatment
      programmes.

PMID- 14690883
TI  - Craving for cigarettes among low and high dependent smokers: impact of norharman.
AB  - Besides nicotine, other chemicals in tobacco smoke, such as norharman, may
      contribute to the addictive properties of cigarettes. More specifically, elevated
      blood plasma levels of norharman may reduce feelings of craving among tobacco
      dependent individuals. To test this hypothesis, plasma concentrations of
      norharman were measured in 38 male smokers (at least 15 cigarettes per day) at
      three time-points on 3 different days spread over a 4-month period. The first
      measurement (T0) was conducted in the morning at 8.30 a.m., after 12 hours of
      smoking abstinence. The T1 and T2 measurements were conducted at 13.00 p.m. and
      16.30 p.m., during a period of ad libitum smoking (after the T0 measurement,
      participants were not restricted in their smoking behaviour). At each of the nine
      time-points, craving was assessed by means of a shortened version of the
      Questionnaire of Smoking Urges. The Fagerstrom Test of Nicotine Dependence was
      used to obtain an indication of nicotine dependence. The results showed that,
      after a period of smoking abstinence, craving was stronger in those with a high
      tobacco dependence than in those with a low tobacco dependence. After resumption
      of smoking, craving declined to a similar low level in both low and high
      dependent smokers. Measurements during periods of ad libitum smoking indicate
      that plasma levels of norharman are related negatively to craving among low
      nicotine-dependent smokers, but not among high dependent smokers.

PMID- 14690885
TI  - Is health a right or common currency: a missed opportunity for Europe?

PMID- 14690887
TI  - To think or not to think: two pathways towards persuasion by short films on AIDS
      prevention.
AB  - Health messages are designed to stimulate an active cognitive process in those
      audiences generally with little involvement. The Elaboration Likelihood Model by
      Petty and Cacioppo sustains that subjects with high involvement and those with
      low involvement react differently to the persuasive message to which they are
      exposed. One efficient way to capture the attention of the low involvement
      audiences is to insert the messages within an entertainment context. Our study
      attempted to analyze affective and cognitive processes to explain the impact of
      these new formats, fictional shorts for HIV/AIDS prevention. A 2 x 2 factorial
      design was used, with involvement in the AIDS issue (high/low) and the type of
      format (musical/dialogue) as independent variables. The finding showed the better
      the quality of the short (with dialogue style) the more negative affectivity was
      stimulated, also the more cognitive processing was induced, and a more favorable
      attitude towards preventive behavior was stimulated.

PMID- 14690888
TI  - The determinants and consequences of information seeking among cancer patients.
AB  - This research was designed to examine information seeking behavior among cancer
      patients. We present a model which identifies the determinants and consequences
      of information seeking and, in turn, examines the effects of prior variables on
      four outcome variables: whether patients discussed with their physicians
      information that they received from other sources, whether the information they
      obtained helped them make decisions about treatment or care, whether the patient
      sought a second opinion about his/her diagnosis or treatment, and changes in self
      reported stress levels from diagnosis to the time of interview. The model is
      estimated separately for three groups: patients who sought information from
      multiple sources including the National Cancer Institute's Cancer Information
      Service, patients who sought information from multiple sources but did not call
      the Cancer Information Service, and patients who did not seek information other
      than from their physician(s). We discuss variables that have similar impacts on
      outcome variables in all three groups as well as variables that operate
      differently within the groups. The results indicate that the desire for
      information and the desire for involvement in medical care decisions are
      independent factors. Some patients have a strong desire for both information and
      involvement in making health care decisions. These patients actively seek
      involvement in their treatment plans. Other patients, however, want to be
      informed about their disease and treatment but prefer to delegate most decision
      making to their physicians. Still other patients choose to delegate information
      gathering and decision making exclusively to their physicians. We discuss the
      implications of these results for both patients and providers.

PMID- 14690889
TI  - Transcending intractable conflict in health care: an exploratory study of
      communication and conflict management among anesthesia providers.
AB  - This paper explores the contrast between the longstanding, intractable conflict
      between two anesthesia providers and the cooperation of many individual nurse
      anesthetists and anesthesiologists working side-by-side to provide safe,
      effective anesthesia. Analysis of interview transcripts reveals that
      communication among anesthesia nurses and anesthesiologists may enact or
      transcend the conflict. This article proposes recommendations for improving
      communication between anesthesiologists and certified registered nurse
      anesthetists in particular and de-escalating intractable conflict in general. It
      also contributes to communication theory in intractable conflict by examining how
      individual, interpersonal conflict management interactions lead to either
      transcendence or enactment of the larger group conflict.

PMID- 14690890
TI  - Let's talk about sex: how comfortable discussions about sex impact teen sexual
      behavior.
AB  - A secondary analysis of data from 1,039 Latino adolescents who participated in a
      study of a sex education program was conducted to examine the impact of
      comfortable communication about sex on intended and actual sexual behavior.
      Results indicate that Latino adolescents have a broad communicative network,
      including friends, dating partners, and extended family members, with whom they
      talk about sex. Regression analyses suggest comfortable sexual communication is
      predictive of less likelihood of being sexually active, older at first
      intercourse, and increased intentions to delay intercourse.

PMID- 14690891
TI  - Communication from a human rights perspective: responding to the HIV/AIDS
      pandemic in eastern and southern Africa. A working paper for use in HIV and AIDS
      programmes.

PMID- 14690962
TI  - Women and alcohol: keeping control. In deciding whether or how much to drink, you
      must weigh the risks and benefits--physical, mental, and social.

PMID- 14690963
TI  - Caregiving: strategies for caring for someone with Alzheimer's disease. Learning
      how to manage Alzheimer's-related behaviors can ease the burden for both the
      person with dementia and the family.

PMID- 14690964
TI  - Go with the grain, the whole grain.

PMID- 14690965
TI  - Partners in resistance: strength and power.

PMID- 14690966
TI  - By the way, doctor. I'm five years into menopause. Recently my breasts became
      tender and I noticed vaginal secretions, but no bleeding--as if I were about to
      have a period. Should I be concerned?

PMID- 14690967
TI  - By the way, doctor. I've had a burning sensation near the entrance to my vagina
      for about three years. After several tests, my doctor said I probably have
      vulvodynia. Can you tell me what causes it? Is there a cure?

PMID- 14690968
TI  - High blood pressure. New definitions, new priorities.

PMID- 14690969
TI  - Does sexual activity keep the prostate healthy?

PMID- 14690970
TI  - Less invasive surgery for prostate cancer.

PMID- 14690971
TI  - On call. I love beef, but I've been eating less of it since reading Harvard Men's
      Health Watch. Lately, however, I've been hearing about grass-fed beef. Do you
      think it's any healthier?

PMID- 14690972
TI  - Autism mysteries: new clues.

PMID- 14690973
TI  - Alzheimer's disease: a progress report, Part II. The continuing search for
      treatments and persistent hopes for prevention.

PMID- 14690974
TI  - Should children take antidepressants?

PMID- 14690975
TI  - How effective is Alcoholics Anonymous?

PMID- 14690976
TI  - Questions & answers. I've been reading conflicting reports about the role fo
      testosterone in depression. Does it have a place in the treatment of depressed
      men?

PMID- 14690977
TI  - Top 10 health stories of 2003.

PMID- 14690978
TI  - Yoga gets into a popular position. Once a spiritual journey for the few, yoga is
      now just a good workout for the many.

PMID- 14690979
TI  - Got milk? No thanks! Up to 20% of Americans believe they're lactose intolerant.
      Just how intolerant varies with the person and the food.

PMID- 14690980
TI  - Fish is heart to beat.

PMID- 14690981
TI  - By the way, doctor. My husband's total cholesterol was 71 for a few months. he
      cut back on his statin and now it's in the low 90s. His HDL is 50 and his LDL in
      the 40s. Should we be worried about such low levels?

PMID- 14690982
TI  - By the way, doctor. I'm 72, with no history of heart trouble. But my cholesterol
      is in the 220s, and I have been taking Lipitor for three years. I am thinking
      about buying a home defibrillator, primarily for myself but also for any
      emergency (although my wife is 52 and in excellent health). What's your advice?

PMID- 14690983
TI  - By the way, doctor. I've been on warfarin (Coumadin) since 1979 after having a
      Starr-Edwards valve put in. The cardiologist insists on aggressive therapy and
      wants my INR at 3.5. But I've had several serious bleeds in the past year and was
      hospitalized three times. What's the current thinking about adequate INR levels
      for patients with metal heart valves?

PMID- 14690984
TI  - Choose the statin that's right for you.
AB  - With a new cholesterol-lowering statin vying for your attention, keep in mind
      that which one you take isn't nearly as important as whether you take it every
      day and how you help it do its work.

PMID- 14690985
TI  - 10 steps for coping with a chronic condition. It pays to organize your approach
      to heart disease or any chronic medical problem.

PMID- 14690986
TI  - Are you getting enough magnesium? Low levels of this key mineral may cause or
      worsen some heart problems.

PMID- 14690987
TI  - Don't fade away with heart failure. Changes wrought by heart failure can attack
      your appetite and whittle away your weight. Some simple steps can help.

PMID- 14690988
TI  - Ask the doctor. I am a fit and healthy 42-year-old man. So I was disturbed when
      my latest electrocardiogram said I had "ST elevation consistent with early
      repolarization." I know from reading the Heart Letter that ST elevation can mean
      a heart attack, although I don't think I have had one of these. Should I be
      worried about this?

PMID- 14690989
TI  - Ask the doctor. Instead of nibbling on chips or crackers, I usually snack on
      nuts. I'm on a low-salt diet for high blood pressure, so I buy raw nuts at the
      store and roast them at home. Does this affect their fat or vitamin content?

PMID- 14690991
TI  - Integrating the social and behavioral sciences in an undergraduate medical
      curriculum: the UCSF essential core.
AB  - Dramatic global-migration patterns over recent decades have forever changed the
      racial, ethnic, social, and cultural makeup of the people of the United States.
      Simultaneously, the patterns of disease and risk factor distribution within the
      U.S. population are changing in ways that accentuate the role of lifestyle,
      behavior, and social and economic differences in the onset and outcomes of
      disease. Medical school curricula must prepare students to address these
      demographic realities. The University of California, San Francisco's (UCSF's)
      redesigned curriculum, launched in September 2001, integrates social, behavioral,
      and biomedical science education in an early and sustained way. The traditional
      undergraduate medical structure of two years of basic science plus two years of
      clinical rotations was replaced with a model divided into three stages spanning
      four years: the Essential Core, the Clinical Core, and Advanced Studies. The
      authors summarize the role of the social and behavioral sciences in the UCSF
      Essential Core-the first 16 months of instruction divided into integrated blocks,
      each centered on clinical cases. Basic thematic areas (e.g., behavior change,
      health disparities), content illustrations (e.g., Introduction to the
      Biopsychosocial Model, The Culture of Medicine), and process considerations
      (e.g., integration, content order, evaluations) are presented. Special challenges
      and limitations are also discussed.

PMID- 14690992
TI  - Faculty and the observation of trainees' clinical skills: problems and
      opportunities.
AB  - The clinical skills of medical interviewing, physical examination, and counseling
      remain vital to the effective care of patients, yet research continues to
      document serious deficiencies in clinical skills among students and residents.
      The most important method of evaluation is the direct observation of trainees
      performing these clinical skills. Standardized patients and other simulation
      technologies are important and reliable tools for teaching clinical skills and
      evaluating competence and will be incorporated in the near future as part of the
      United States Medical Licensing Examination. Standardized patients and
      simulation, however, cannot and should not replace the direct observation by
      faculty of trainees' clinical skills with actual patients. Faculty are in the
      best position to document improvement over time and to certify trainees have
      attained sophisticated levels of skill in medical interviewing, physical
      examination, and counseling. Unfortunately, current evidence suggests significant
      deficiencies in faculty direct observation evaluation skills. The author outlines
      the nature of the problems in clinical skills and their evaluation by faculty and
      ends with recommendations to improve the current state of faculty skills in
      evaluation.

PMID- 14690993
TI  - Bringing good teaching cases "to life": a simulator-based medical education
      service.
AB  - Realistic medical simulation has expanded worldwide over the last decade. Such
      technology is playing an increasing role in medical education not merely because
      simulator sessions are enjoyable, but because they can provide an enhanced
      environment for experiential learning and reflective thought. High-fidelity
      patient simulators allow students of all levels to "practice" medicine without
      risk, providing a natural framework for the integration of basic and clinical
      science in a safe environment. Often described as "flight simulation for
      doctors," the rationale, utility, and range of medical simulations have been
      described elsewhere, yet the challenges of integrating this technology into the
      medical school curriculum have received little attention. The authors report how
      Harvard Medical School established an on-campus simulator program for students in
      2001, building on the work of the Center for Medical Simulation in Boston. As an
      overarching structure for the process, faculty and residents developed a
      simulator-based "medical education service"-like any other medical teaching
      service, but designed exclusively to help students learn on the simulator
      alongside a clinician-mentor, on demand. Initial evaluations among both
      preclinical and clinical students suggest that simulation is highly accepted and
      increasingly demanded. For some learners, simulation may allow complex
      information to be understood and retained more efficiently than can occur with
      traditional methods. Moreover, the process outlined here suggests that simulation
      can be integrated into existing curricula of almost any medical school or
      teaching hospital in an efficient and cost-effective manner.

PMID- 14690994
TI  - Use of standardized patients to enhance a psychiatry clerkship.
AB  - Changes in psychiatric health care delivery driven by such major shifts as
      deinstitutionalization, community-based care, and managed care have greatly
      altered the educational milieu for third-year psychiatry clerkships. Students may
      be assigned exclusively to alcohol and substance abuse treatment units,
      consultation-liaison services, or outpatient clinics, and may not have as broad
      an exposure as is desirable to patients with a variety of psychiatric illnesses.
      The authors describe a pilot course they developed in 2001, Clinical Psychiatric
      Assessment and Diagnosis, for third-year medical students at the Uniformed
      Services University of the Health Sciences medical school. The course uses
      standardized patients (SPs) to help students gain broader clinical experience. In
      psychiatry, a growing body of literature supports the acceptability, reliability,
      and validity of objective structured clinical examination assessment using SPs
      for medical students. Only a few articles report the use of SPs to primarily
      teach psychiatry instead of evaluating student proficiency in clinical
      psychiatry. Since this course was developed, the National Board of Medical
      Examiners announced that all medical students will be required to pass a clinical
      skills test in order to practice medicine, beginning with the class of 2005. The
      examination will use SPs modeling different clinical scenarios. In light of this
      change, many medical schools may have to reevaluate and possibly revamp their
      curriculums to insure sufficient acquisition of clinical skills in different
      specialties. The use of SPs in psychiatry could provide an effective, primary
      clinical teaching experience to address this new requirement as well.

PMID- 14690995
TI  - Training U.S. medical students to care for the chronically ill.
AB  - PURPOSE: The growing prevalence of chronic illness has important implications for
      the training of all physicians. The authors assessed the degree to which
      undergraduate medical curricula explicitly address chronic care competencies
      selected through literature and expert review. METHOD: In 2001, trained student
      assistants interviewed directors of required medical school courses (internal
      medicine, pediatrics, family practice, and ambulatory care clerkships;
      longitudinal care; and other relevant courses) at 16 representative U.S. medical
      schools sampled by geography, curriculum reform activity, and primary care
      orientation of graduates. Course directors were asked whether chronic care
      competencies were addressed using specific curricular methods (written
      objectives, course materials, observational evaluations, written/oral
      examinations, other required course activities), and to rate the importance (1 =
      not important; 5 = essential) of each competency for their course and for the
      overall undergraduate curriculum. RESULTS: All 70 eligible course directors
      responded. Of 49 chronic care competencies, 29 (59%) received mean importance
      ratings for a course of >/=3, but only 14 (29%) were addressed using two or more
      specific curricular methods. Course directors gave highest importance ratings
      (mean > 3.9) to screening for abuse, awareness of patients' sociocultural
      perspectives, and protecting patients' confidentiality. They gave lowest
      importance ratings (mean </= 2.6) to knowing strategies to maximize patients'
      potential, ability to discuss alternative information sources, and ability to
      assess equipment needs. Their importance ratings correlated only moderately with
      the number of curricular methods used to address each competency (r(2) = 0.27
      0.80, p <.05). CONCLUSION: Course directors agreed about the importance of many
      competencies in chronic care but reported considerable variation in how they
      addressed competencies in their courses. Medical schools can improve training in
      chronic care by paying greater attention to specific methods for addressing
      important chronic care competencies.

PMID- 14690996
TI  - Effectiveness of the one-minute preceptor model for diagnosing the patient and
      the learner: proof of concept.
AB  - PURPOSE: To compare the One-Minute Preceptor (OMP) and traditional models of
      ambulatory teaching in terms of the preceptors' (1) ability to correctly diagnose
      patients' medical problems, (2) ability to rate students' skills and confidence
      in doing so, and (3) satisfaction with both models. METHOD: A within-groups
      experimental design study was conducted with 116 preceptors at seven universities
      in 2000. Participants viewed scripted, videotaped precepting encounters of both
      models using two cases and were asked to rate students' abilities, their
      confidence in rating the students' abilities, and the effectiveness and
      efficiency of the teaching encounters. RESULTS: Preceptors who viewed the
      videotapes of the OMP model were equally or better able to correctly diagnose the
      patients' medical conditions than those viewing the traditional model. Preceptors
      viewing the OMP rated students' abilities higher on history taking/physical
      examination, presentations, clinical reasoning, and fund of knowledge than did
      those viewing the traditional model. Preceptors viewing the OMP rated themselves
      as more confident in rating students' abilities in presentation, clinical
      reasoning, and fund of knowledge. Preceptors rated the OMP as more effective and
      more efficient than the traditional model. CONCLUSIONS: Preceptors viewing
      scripted, videotaped teaching encounters using the OMP model were equal to or
      better able to correctly diagnose patients' medical problems, had greater self
      confidence in rating students, and rated the encounter as more effective and
      efficient than when viewing the traditional model.

PMID- 14690997
TI  - Teaching points identified by preceptors observing one-minute preceptor and
      traditional preceptor encounters.
AB  - PURPOSE: This study examined the teaching points made by preceptors in response
      to two videotaped teaching encounters to determine if (1) different preceptors
      use similar teaching points in response to the same case, (2) preceptors'
      teaching points vary by case, and (3) preceptors' teaching points vary by
      teaching model (One-Minute Preceptor and traditional preceptor models). METHOD:
      Preceptors (n = 116) at seven universities participated in a within-groups
      experimental design study in 2000. The preceptors viewed videotaped encounters
      depicting two cases and two precepting models. They were asked to list two
      teaching points after viewing the initial case presentations and after the
      teaching encounters were completed. Frequency of teaching points listed by
      preceptors was examined for each case and teaching model. Teaching points were
      coded using qualitative methods and then analyzed using repeated-measures
      analysis of variance. RESULTS: Of the 843 total teaching points identified by
      preceptors, 63 were discrete teaching points that were aggregated into 15
      categories. Most preceptors (82%) listed three to five separate teaching points,
      which varied significantly by case and model. Those observing the traditional
      precepting model were more likely to teach generic skills such as history-taking
      skills, presentation skills, and risk factors, and those observing the One-Minute
      Preceptor were more likely to teach about the illness focusing on a broader
      differential diagnosis, further diagnostic tests, and the natural presentation of
      disease. CONCLUSIONS: Preceptors use three to five common teaching points that
      vary by case and teaching model. The One-Minute Preceptor model shifted teaching
      points away from generic clinical skills toward disease-specific teaching.

PMID- 14690998
TI  - Do clerkship directors think medical students are prepared for the clerkship
      years?
AB  - PURPOSE: Educators have begun to question whether medical students are adequately
      prepared for the core clerkships. Inadequate preclerkship preparation may hinder
      learning and may be predictive of future achievement. This study assessed and
      compared the views of clerkship directors regarding student preparation for the
      core clinical clerkships in six key competencies. METHOD: In 2002, a national
      survey was conducted of 190 clerkship directors in internal medicine, family
      medicine, pediatrics, surgery, obstetrics/gynecology, and psychiatry from 32 U.S.
      medical schools. Clerkship directors were asked to report their views on the
      appropriate level of student preparation needed to begin the core clinical
      clerkships (none, minimal, intermediate, advanced), and the adequacy of that
      preparation (ranging from "much less" to "much more than necessary") in six key
      clinical competencies. RESULTS: A total of 140 clerkship directors responded
      (74%). The majority reported that students need at least intermediate ability in
      five of six competencies: communication (96%), professionalism (96%),
      interviewing/physical examination (78%), life-cycle stages (57%),
      epidemiology/probabilistic thinking (56%), and systems of care (27%). Thirty to
      fifty percent of clerkship directors felt students are less prepared than
      necessary in the six competencies. Views were similar across all specialties and
      generally did not differ by other clerkship director characteristics.
      CONCLUSIONS: Almost half of clerkship directors were concerned that students do
      not receive adequate preparation in key competencies before starting the core
      clinical clerkships. Many medical schools may need to give more attention to the
      preclerkship preparation of students in these high-priority areas.

PMID- 14690999
TI  - Evaluating the Texas Statewide Family Practice Preceptorship Program, 1992-2000.
AB  - PURPOSE: Since 1979, the Texas Statewide Family Practice Preceptorship Program
      (TSFPPP) has conducted ambulatory preceptorships to increase the number of
      medical students selecting family practice residencies. The authors describe the
      evaluation of the TSFPPP's efficacy in terms of four evaluation questions and
      outcome measures identified by program users from eight Texas medical schools.
      METHOD: The authors compared the proportion of 10,081 Texas medical school
      students graduating from 1992-2000 who chose family practice or other primary
      care residencies following participation or nonparticipation in the TSFPPP's
      preclinical and clinical programs. RESULTS: The proportion of students choosing
      family practice residencies among TSFPPP participants was significantly greater
      than among nonparticipants. Participation in the TSFPPP was associated with an
      increased choice of a family practice residency for students who were involved in
      the TSFPPP at the preclinical level (odds ratio [OR], 1.62; 95% confidence
      interval [CI], 1.41-1.87); the clinical level (OR, 2.31; 95% CI, 1.99-2.68); and
      both levels (OR, 4.98; 95% CI, 3.75-6.68) compared to non-TSFPPP participation.
      There was a 44% increase in preceptors willing to teach medical students.
      CONCLUSIONS: Participation in the TSFPPP is associated with a greater likelihood
      of students selecting a family practice residency. The interinstitutional
      approach to analyzing effects of the preceptorship on students' specialty choices
      focuses attention on primary care issues that, in the long run, may affect an
      entire state's health care delivery system.

PMID- 14691001
TI  - Ambulatory care education: how do academic medical centers, affiliated residency
      teaching sites, and community-based practices compare?
AB  - PURPOSE: Little is known about how different ambulatory sites compare as clinical
      educational settings. The authors used students' log data to compare the
      educational content and processes in academic medical center-based clinics
      (AMCs), affiliated residency teaching sites (ARTs), and local community-based
      practices (CBPs) at one medical school. METHOD: Students recorded their
      experiences with symptoms, counseling, procedures, and common medical conditions
      as well as characteristics of the learning process during a required eight-week
      third-year ambulatory clerkship in family medicine. Descriptive statistics, chi
      square for differences in categorical variables, and analysis of variance and
      multivariate analysis of variance for differences in continuous variables were
      used to compare the educational settings. RESULTS: Over 9,000 encounters were
      analyzed; 29.7% occurred in AMCs, 14.8% in ARTs, and 55.5% in CBPs. The
      proportion of continuity visits was lowest in the AMCs and highest in CBPs (13%
      versus 22%, respectively; p <.01). Students saw almost 57,000 symptoms and
      conditions. Of 19 symptoms compared, seven differed significantly among the three
      settings: back pain, cough, dyspnea, ENT (ears, nose, throat problems), fatigue,
      knee pain, and vomiting. All but one of these were least likely to occur in ARTs.
      Procedures were performed more frequently, whereas counseling skills were called
      upon less frequently in CBPs. Students reported being more likely to work
      unobserved while conducting physical examinations in ARTs and CBPs. Amount of
      feedback provided on clinical skills did not differ, but students reported
      receiving more teaching about patient management in ARTs and AMCs versus CBPs
      (74%, 72%, and 66% of encounters, respectively; p <.01). CONCLUSIONS: Academic
      and community settings can complement each other as learning sites for an
      ambulatory clerkship in family medicine, and common curricular expectations can
      be achieved. Settings' differences and similarities should be taken into account
      when developing, implementing, or revising clerkship programs and should be
      considered with students' interests and previous clinical experiences before
      assigning students to a teaching site.

PMID- 14691002
TI  - Medical student evaluation of the quality of hospitalist and nonhospitalist
      teaching faculty on inpatient medicine rotations.
AB  - PURPOSE: To evaluate the impact of academic hospitalists on third-year medical
      students during inpatient medicine rotations. METHOD: The authors conducted a
      retrospective quantitative assessment of medical student evaluations of
      hospitalist and nonhospitalist Department of Medicine faculty at Oregon Health &
      Science University, for the 1998-00 academic years. Using a nine-point Likert
      type scale, students evaluated the faculty on the following characteristics:
      communication of rotation goals, establishing a favorable learning climate, use
      of educational time, teaching style, evaluation and feedback, contributions to
      the student's growth and development, and overall effectiveness as a clinical
      teacher. RESULTS: A total of 138 students rotated on the university wards during
      the study period; 100 with hospitalists, and 38 with nonhospitalists. Of these
      students, 99 (71.7%) returned evaluations. The hospitalists received higher
      numeric evaluations for all individual attending characteristics. Significance
      was achieved comparing communication of goals (p =.011), effectiveness as a
      clinical teacher (p =.016), and for the combined analysis of all parameters (p
      <.001). Despite lack of achieving statistical significance, there was a trend
      toward hospitalists being more likely to contribute to the medical student's
      perception of growth and development during the period evaluated (p =.065).
      CONCLUSIONS: In addition to performing the responsibilities required of full-time
      hospital-based physicians, hospitalists were able to provide at least as positive
      an educational experience as did highly rated nonhospitalist teaching faculty and
      in some areas performed better. A hospitalist model can be an effective method of
      delivering inpatient education to medical students.

PMID- 14691003
TI  - "The mirror" and "the village": a new method for teaching practice-based learning
      and improvement and systems-based practice.
AB  - PURPOSE: Practice-based learning and improvement (PBLI) and systems-based
      practice (SBP) may be conceptually difficult for both residents and faculty.
      Methods for introducing these concepts are needed if PBLI and SBP are to be
      incorporated into education and practice. METHOD: In 2001, PBLI and SBP were
      introduced at Johns Hopkins Bayview Medical Center in Baltimore, Maryland, using
      the metaphors "the mirror" and "the village." PBLI was likened to residents'
      holding up a mirror to document, assess, and improve their practice. Specific
      tools for residents (e.g., weekly morbidity and mortality morning reports,
      continuity clinic chart self-audits, and resident learning portfolios) became the
      mirrors. SBP was introduced through specific training activities (e.g.,
      multidisciplinary patient care rounds, nursing evaluations, and quality
      assessment-systems improvement exercises) using the metaphor of the village made
      famous by Hillary Clinton in the phrase: "It takes a village to raise a child."
      Residents completed a questionnaire in which they rated these initiatives' impact
      on their training. RESULTS: The majority of residents who participated in
      specific activities agreed that quality assessment-systems improvement exercises
      (92.9%), multidisciplinary rounds (92.1%), morbidity and mortality morning
      reports (86.8%), clinic chart self-audits (76.4%), and nursing evaluations
      (52.8%) helped to improve their proficiency in specific aspects of PBLI and SBP.
      Residents' retrospective self-assessments of their PBLI abilities demonstrated
      significant improvement after the introduction of specific training activities.
      CONCLUSIONS: PBLI and SBP can be introduced effectively in residency training by
      incorporating specific activities that use the metaphors of the mirror and the
      village.

PMID- 14691004
TI  - Medical students' use of information resources: is the digital age dawning?
AB  - PURPOSE: One of the many challenges clinicians face is applying growing medical
      knowledge to specific patients; however, there is an information gap between
      information needs and delivery. Digital information resources could potentially
      bridge this gap. Because most medical students are exposed to personal computers
      throughout their education, this study postulated that students may be more
      comfortable using computer-based information resources within clinical
      interactions. METHOD: In 2001, the authors monitored second-year medical
      students' use of a unique digital textbook, UpToDate, as they transitioned from
      preclinical to clinical years at the University of Iowa Roy J. and Lucille A.
      Carver College of Medicine. In 2002, at the end of their third year, students
      were surveyed about their preferred clinical information resources. RESULTS:
      Medical students rapidly adopted UpToDate as a clinical resource during their
      clinical clerkship as evidenced by a rapid growth in the electronic textbook's
      use. One hundred sixteen of a possible 154 students (75%) responded to the
      survey. More than 85% of respondents identified electronic sources as their
      primary resource (UpToDate 53%, MDConsult 33%; p <.001 when compared to paper
      resources). They also reported using the information resources on a daily basis
      and requiring less than 15 minutes to answer most of their clinical questions.
      CONCLUSIONS: This study clearly demonstrates that medical students embrace and
      use electronic information resources much more than has been reported among
      practicing clinicians. The current generation of students may be the leaders in a
      medical culture shift from paper to electronic resources.

PMID- 14691006
TI  - Medicine and the arts. A summer dilemma.

PMID- 14691005
TI  - Student attitudes about a clinical experience in abortion care during the
      obstetrics and gynecology clerkship.
AB  - PURPOSE: An optional half-day clinical experience in abortion care was offered to
      third-year medical students rotating through the core obstetrics and gynecology
      (Ob/Gyn) clerkship at the University of New Mexico to improve education about
      women's reproductive health. This study using survey methods was conducted to
      rate the acceptability of the clinical experience and to document any changes in
      students' attitudes toward women's access to abortion. METHOD: All 145 students
      who rotated through the Ob/Gyn clerkship between March 2000 and March 2002 were
      provided an 11-item, confidential questionnaire to complete. Students who did not
      participate in the abortion care experience were asked questions about their
      reasons for declining participation; students who did participate were asked
      questions about the value of the experience. RESULTS: Of the 145 students who
      rotated through the clerkship during the study period, 126 (87%) completed the
      questionnaire. Of these students, 86 (68%) participated in the clinical
      experience and 40 (32%) did not. The majority of students who participated in the
      clinical experience rated it very highly. Of the 86 students who participated in
      the clinical experience, 33 (38%) reported a change in their attitudes about
      abortion; 31 (94%) of these became more supportive of women's access to abortion
      services. CONCLUSION: Clinical experiences in abortion care are acceptable to and
      valued by a diverse group of medical students and should be offered at medical
      schools throughout the United States.

PMID- 14691008
TI  - Disparate effects of thyroid hormone on actions of epidermal growth factor and
      transforming growth factor-alpha are mediated by 3',5'-cyclic adenosine 5'
      monophosphate-dependent protein kinase II.
AB  - Epidermal growth factor (EGF) and TGFalpha share the same plasma membrane
      receptor. In the present studies in HeLa cells, both EGF and TGFalpha caused MAPK
      (ERK1/2) activation and expression of the immediate-early gene c-fos. Thyroid
      hormone (T(4)) nongenomically enhanced EGF- and TGFalpha-induced MAPK activation.
      This T(4) action was duplicated by T(4)-agarose and blocked by
      tetraiodothyroacetic acid, which inhibits binding of T(4) to plasma membranes.
      TGFalpha-induced MAPK activation was potentiated by 8-bromo-cyclic adenosine
      monophosphate (8-Br-cAMP) but not 8-chloro-cyclic adenosine monophosphate.
      TGFalpha, T(4), and 8-Br-cAMP each caused protein kinase A (PKA) II serine
      phosphorylation, whereas phosphorylation of PKA-II was not seen in cells treated
      with EGF or 8-chloro-cyclic adenosine monophosphate. In a PKA activity assay, the
      enzyme was stimulated by T(4), EGF, and TGFalpha; T(4) enhanced the effect of
      TGFalpha but not that of EGF. T(4), although it potentiated c-fos gene expression
      in EGF-treated cells, suppressed this effect in cells treated with TGFalpha.
      Cells exposed to 8-Br-cAMP also inhibited TGFalpha-stimulated c-fos expression.
      Studies of cell proliferation indicated that T(4) potentiated EGF action but
      inhibited that effect in TGFalpha-treated cells. The disparate effects of T(4) on
      actions of EGF and TGFalpha, which share the same cell surface receptor, are
      mediated by hormone phosphorylation and activation of PKA-II.

PMID- 14691009
TI  - The adrenal secretory serine protease AsP is a short secretory isoform of the
      transmembrane airway trypsin-like protease.
AB  - To further elucidate the role of proteases capable of cleaving N-terminal
      proopiomelanocortin (N-POMC)-derived peptides, we have cloned two cDNAs encoding
      isoforms of the airway trypsin-like protease (AT) from mouse (MAT) and rat (RAT),
      respectively. The open reading frames comprise 417 amino acids (aa) and 279 aa.
      The mouse AT gene was located at chromosome 5E1 and contains 10 exons. The longer
      isoform, which we designated MAT1 and RAT1, has a simple type II transmembrane
      protein structure, consisting of a short cytoplasmic domain, a transmembrane
      domain, a SEA (63-kDa sea urchin sperm protein, enteropeptidase, agrin) module,
      and a serine protease domain. The human homolog of MAT1 and RAT1 is the human AT
      (HAT). The shorter isoform, designated MAT2 and RAT2, which contains an
      alternative N terminus, was formerly described in the rat as adrenal secretory
      serine protease (AsP) and has been shown to be involved in the processing of N
      POMC-derived peptides. In contrast to the long isoform, neither MAT2 and RAT2
      (AsP) contain a transmembrane domain nor a SEA domain but an N-terminal signal
      peptide to direct the enzyme to the secretory pathway. The C terminus, covering
      the catalytic triad, is identical in both isoforms. Immunohistochemically,
      MAT/RAT was predominantly expressed in tissues of the upper gastrointestinal and
      the respiratory tract-but also in the adrenal gland. Moreover, isoform-specific
      RT-PCR and quantitative PCR analysis revealed a complex expression pattern of the
      two isoforms with differences between mice and rats. These findings indicate a
      multifunctional role of these proteases beyond adrenal proliferation.

PMID- 14691010
TI  - Oxytocin receptor is expressed in the penis and mediates an estrogen-dependent
      smooth muscle contractility.
AB  - Oxytocin (OT) is released by the posterior pituitary during male orgasm and is
      supposed to participate in the ejaculatory process. We now report evidence
      demonstrating the presence of an OT receptor gene (real-time RT-PCR and Northern
      blot) and protein (immunohistochemistry, Western blot, and binding studies)
      expression in the rabbit and human corpus cavernosum (CC) and its possible
      involvement in postorgasmic penile detumescence. OT receptor is expressed in the
      penis at a concentration similar to that present in other portions of the male
      genital tract and mediates CC contractility. OT-induced CC contractility is
      clearly regulated by the changing sex steroid milieu. In fact, we found that in a
      rabbit model of hypogonadotropic hypogonadism (induced by a single administration
      of the long-acting GnRH agonist triptorelin pamoate, 2.9 mg/kg), OT
      responsiveness was strongly reduced and was completely restored by estradiol
      valerate (3.3 mg/kg weekly), but not by testosterone enanthate (30 mg/kg weekly).
      As we found that CC expresses both subtypes of estrogen receptors and P450
      aromatase, we hypothesized a physiological role for endogenous estrogens in
      regulating OT responsiveness. We therefore treated adult rabbits with an
      aromatase inhibitor (letrozole, 2.5 mg/kg) or an antiestrogen (tamoxifen, 0.25
      mg/kg) for 3 wk. Both treatments significantly reduced CC responsiveness to OT
      stimulation. In conclusion, these findings indicate that OT might participate in
      inducing postorgasmic penile flaccidity and suggest a new role for estrogens in
      the male: regulation of CC responsiveness to OT.

PMID- 14691012
TI  - Glucocorticoids act directly on osteoblasts and osteocytes to induce their
      apoptosis and reduce bone formation and strength.
AB  - Whether the negative impact of excess glucocorticoids on the skeleton is due to
      direct effects on bone cells, indirect effects on extraskeletal tissues, or both
      is unknown. To determine the contribution of direct effects of glucocorticoids on
      osteoblastic/osteocytic cells in vivo, we blocked glucocorticoid action on these
      cells via transgenic expression of 11beta-hydroxysteroid dehydrogenase type 2, an
      enzyme that inactivates glucocorticoids. Osteoblast/osteocyte-specific expression
      was achieved by insertion of the 11beta-hydroxysteroid dehydrogenase type 2 cDNA
      downstream from the osteoblast-specific osteocalcin promoter. The transgene did
      not affect normal bone development or turnover as demonstrated by identical bone
      density, strength, and histomorphometry in adult transgenic and wild-type
      animals. Administration of excess glucocorticoids induced equivalent bone loss in
      wild-type and transgenic mice. As expected, cancellous osteoclasts were
      unaffected by the transgene. However, the increase in osteoblast apoptosis that
      occurred in wild-type mice was prevented in transgenic mice. Consistent with
      this, osteoblasts, osteoid area, and bone formation rate were significantly
      higher in glucocorticoid-treated transgenic mice compared with glucocorticoid
      treated wild-type mice. Glucocorticoid-induced osteocyte apoptosis was also
      prevented in transgenic mice. Strikingly, the loss of vertebral compression
      strength observed in glucocorticoid-treated wild-type mice was prevented in the
      transgenic mice, despite equivalent bone loss. These results demonstrate for the
      first time that excess glucocorticoids directly affect bone forming cells in
      vivo. Furthermore, our results suggest that glucocorticoid-induced loss of bone
      strength results in part from increased death of osteocytes, independent of bone
      loss.

PMID- 14691011
TI  - Inhibition of death-receptor mediated apoptosis in human adipocytes by the
      insulin-like growth factor I (IGF-I)/IGF-I receptor autocrine circuit.
AB  - Adipose tissue mass is reflected by the volume and the number of adipocytes and
      is subject to homeostatic regulation involving cell death mechanisms. In this
      study we have investigated the mechanisms of apoptosis in human preadipocytes and
      adipocytes that may play a role in the regulation of adipose tissue mass. We
      found that death receptors (CD95, TNF-related apoptosis-inducing ligand receptors
      1 and 2, and TNF receptor 1) are expressed in human fat cells and that apoptosis
      can be induced by specific ligands. Sensitivity to apoptosis could be stimulated
      by an inhibitor of biosynthesis. In addition, inhibition of auto-/paracrine
      action of IGF-I dramatically sensitizes human adipocytes for death ligand-induced
      apoptosis. Phosphoinositide 3-kinase and, to a weaker extent, p38 MAPK are
      involved in IGF-I-mediated survival. IGF-I protects human fat cells from
      apoptosis by maintaining the expression of antiapoptotic proteins, Bcl-x(L) and
      Fas-associated death domain-like IL-1-converting enzyme inhibitory protein. In
      conclusion, we identified mechanisms of apoptosis induction in human fat cells.
      We furthermore demonstrate that human fat cells protect themselves from apoptosis
      by IGF-I in an auto-/paracrine manner.

PMID- 14691013
TI  - Inhibition of extracellular signal-regulated protein kinase-2 phosphorylation by
      dihydrotestosterone reduces follicle-stimulating hormone-mediated cyclin D2
      messenger ribonucleic acid expression in rat granulosa cells.
AB  - Granulosa cell mitogenesis is critical for the development of normal ovarian
      follicles. FSH and other mitogenic stimuli play a crucial role in this process.
      We have shown that exposing granulosa cells to 5alpha-dihydrotestosterone (DHT)
      reduces forskolin-stimulated cyclin D2 mRNA expression, which leads to cell cycle
      arrest resulting in reduced cell proliferation. The present study investigated
      the signaling molecules upstream of cyclin D2 in FSH-mediated, cAMP-dependent
      signaling pathway that may be negatively affected by DHT, leading to inhibition
      of cell cycle progression. Because ERK is an important molecule in mitogenic
      signaling, the possible effect of DHT on its phosphorylation was examined.
      Granulosa cells from 3-d estradiol-primed immature rats were treated with DHT (90
      ng/ml) for 24 h and subsequently stimulated with forskolin. DHT treatment reduced
      forskolin stimulation of ERK phosphorylation. Although DHT exposure did not
      affect cellular cAMP production in response to forskolin, treating the cells with
      DHT for 24 h significantly reduced protein kinase A activity. DHT also caused a
      reduction in ERK-2 phosphorylation in response to FSH similar to that seen with
      forskolin. Furthermore, blocking ERK phosphorylation as well as DHT treatment
      resulted in a reduction in FSH-stimulated cyclin D2 mRNA expression. From these
      results, we conclude that DHT treatment reduces the FSH-mediated ERK
      phosphorylation in granulosa cells, leading to reduced cyclin D2 mRNA expression
      that culminates in cell cycle arrest.

PMID- 14691014
TI  - A benzimidazole fungicide, benomyl, and its metabolite, carbendazim, induce
      aromatase activity in a human ovarian granulose-like tumor cell line (KGN).
AB  - Endocrine disruptor chemicals are known to cause a range of abnormalities in
      sexual differentiation and reproduction. One mechanism underlying such effects
      may be via alteration of aromatase activity, which is responsible for estrogen
      production. A good screening system for identifying endocrine disruptors has long
      been desired. We have recently established a human ovarian granulosa-like tumor
      cell line, KGN, which possesses a relatively high level of aromatase expression
      and is considered a useful mammalian model for investigating the in vitro effects
      of various chemicals on aromatase activity. In this study we screened 55
      different candidate chemicals for endocrine disruptors by assaying aromatase
      activity. Only benomyl, known as both a benzimidazole fungicide and a microtubule
      interfering agent, was found to induce aromatase activity in association with
      increased levels of aromatase mRNA in KGN cells. The effect of benomyl was
      presumed to be mediated by its metabolite carbendazim, because it produced an
      effect equivalent to that of benomyl. The mechanism underlying the benomyl
      induced increase in aromatase activity appears independent of the cAMP-protein
      kinase A pathway. Treatment with taxol, another class of microtubule-interfering
      agents, also caused induction of aromatase in KGN cells. Both benomyl and taxol
      changed KGN cell morphology, including the development of cell roundness and a
      disorganized network of microtubules. These results indicate that benomyl is a
      potential endocrine disruptor that provides a novel estrogenicity and operates
      through a microtubule-interfering mechanism.

PMID- 14691015
TI  - Post-afterdischarge depolarization does not stimulate prolonged neurohormone
      secretion but is required for activity-dependent stimulation of neurohormone
      biosynthesis from peptidergic neurons.
AB  - Membrane depolarization plays a critical role in stimulating secretion of
      neuropeptides and can also be important in regulating transcriptional and
      translational events that control peptide biosynthesis. The purpose of this study
      was to test the hypothesis that persistent membrane depolarization after the end
      of an electrical afterdischarge plays an important role in stimulating both
      prolonged secretion of egg-laying hormone (ELH) and ELH synthesis from
      peptidergic bag cell neurons of Aplysia. Experimental preparations were treated
      with a low Na(+) solution to rapidly repolarize membrane potential (Vm). Compared
      with control preparations, the low Na(+) solution caused rapid membrane
      repolarization to resting levels, significant shortening of the duration of the
      afterdischarge, and significant decrease in the decay time constant of cytosolic
      Ca(2+) ([Ca(2+)](i)) concentrations, but no effect on peak [Ca(2+)](i), total
      [Ca(2+)](i) above baseline, or duration of elevated [Ca(2+)](i). Contrary to both
      theoretical expectations and findings in other cell types, low Na(+) treatment
      and the resulting premature repolarization of Vm did not inhibit ELH secretion.
      On the other hand, low Na(+) treatment that blocked prolonged depolarization, as
      well as inhibition of Ca(2+) influx, prevented the afterdischarge-induced
      stimulation of ELH synthesis. These findings provide support for membrane
      depolarization acting as a trigger mechanism, rather than a sustained driving
      force, for cellular events that control ELH secretion. It also demonstrates, for
      the first time, a critical role for postdischarge Vm in regulating an important
      aspect of neuroendocrine cell function-that of hormone synthesis.

PMID- 14691016
TI  - Inhibition of steroidogenic response to adrenocorticotropin by leptin:
      implications for the adrenal response to maternal separation in neonatal rats.
AB  - Previous studies have shown that leptin can regulate the adrenocortical axis.
      Neonatal rodents exhibit a period of adrenal hyporesponsiveness to stress in the
      first 2 wk of life, and we determined the role of leptin as a mediator of this
      process. We examined the direct effects of leptin on neonatal adrenal
      steroidogenic responses to ACTH under basal conditions and after 24-h maternal
      separation. In isolated adrenocortical cells from as early as postnatal d 5
      (PND5) and throughout the neonatal period, acute (2.5 h) incubation with leptin
      significantly inhibited ACTH-stimulated corticosterone and aldosterone secretion
      without affecting cAMP production. In PND10 pups, 24-h maternal separation and
      the resulting rapid decline in plasma leptin levels increased basal
      corticosterone and aldosterone secretion in vivo and in isolated cells, but did
      not modify the ability of leptin to inhibit stimulated steroid production in
      vitro. Maternal separation in PND10 pups increased adrenal expression of
      steroidogenic acute regulatory protein (StAR) and peripheral-type benzodiazepine
      receptor (PBR) proteins as well as all steroidogenic enzymes measured (3beta
      hydroxysteroid dehydrogenase, P450C11B1, and P450C11B2). Leptin (1 mg/kg body
      weight, i.p.) replacement during maternal separation did not affect basal
      corticosterone output, but reduced corticosterone secretion and StAR and PBR
      protein expression induced by exogenous ACTH challenge (20 or 80 microg/kg body
      weight, i.p.). These results indicate that leptin inhibits ACTH-stimulated
      secretion of corticosterone and aldosterone, at least through a rapid reduction
      in the expression of StAR and PBR protein in the neonatal adrenal gland. As
      leptin concentrations in pups are controlled to a large extent by the maternal
      diet, these results emphasize the key role of leptin to mediate the maternal
      influence on the adrenocortical axis of the infant.

PMID- 14691017
TI  - Cocaine- and amphetamine-regulated transcript co-contained in thyrotropin
      releasing hormone (TRH) neurons of the hypothalamic paraventricular nucleus
      modulates TRH-induced prolactin secretion.
AB  - TRH synthesized in hypophysiotropic neurons of the hypothalamic paraventricular
      nucleus (PVN) stimulates the release of TSH and prolactin from the anterior
      pituitary gland. Recent data from our laboratories have demonstrated that TRH and
      cocaine- and amphetamine-regulated transcript (CART) are co-contained only in
      hypophysiotropic neurons in the PVN. To determine whether CART and TRH interact
      in the regulation of anterior pituitary function, we have studied the effects of
      CART on TRH-induced release of TSH and prolactin in anterior pituitary cell
      cultures, and the effects of hypo- and hyperthyroidism on CART mRNA in the PVN.
      Dispersed anterior lobe cells from male rats were treated with CART (10(-6), 10(
      8), 10(-10), and 10(-12) m) or TRH (10(-7) m) alone and TRH (10(-7) m) combined
      with various concentrations of CART for 4 h at 37 C. The medium was assayed for
      prolactin and TSH by RIA. TRH resulted in a marked increase of both prolactin and
      TSH release, whereas CART had no effect on prolactin or TSH secretion. When the
      two peptides were used in combination, CART dose-dependently inhibited TRH
      induced prolactin release but had no significant effect on TRH-induced TSH
      release. By semiquantitative analysis of in situ hybridization autoradiographs,
      CART mRNA was significantly elevated in hypothyroid animals, whereas a reduction
      in CART mRNA was observed in hyperthyroid animals compared with euthyroid
      controls. These data raise the possibility that CART expressed in
      hypophysiotropic TRH neurons has an important role in the modulation of TRH
      induced prolactin secretion. Increased secretion of CART may be responsible for
      the reduced TRH-induced prolactin response during hypothyroidism.

PMID- 14691018
TI  - Transplant graft vasculopathy: a dark side of bone marrow stem cells?

PMID- 14691019
TI  - Left ventricular assist devices: bridges to transplantation, recovery, and
      destination for whom?

PMID- 14691020
TI  - Mechanical circulatory support for advanced heart failure: where does it stand in
      2003?

PMID- 14691021
TI  - Editors' commentary: mechanical circulatory support.

PMID- 14691022
TI  - Cardiovascular pharmacogenomics.

PMID- 14691023
TI  - Images in cardiovascular medicine. Santa Claus in the echo lab.

PMID- 14691026
TI  - Coronary artery calcium and cardiac events.

PMID- 14691027
TI  - Prognostic value of coronary artery calcification.

PMID- 14691028
TI  - Fibrinolytic therapy: what size to fit all?

PMID- 14691029
TI  - Infection, endothelial dysfunction, and atherogenesis.

PMID- 14691030
TI  - Aldosterone blockade in patients with acute myocardial infarction.

PMID- 14691031
TI  - Small left ventricular aneurysms in patients with ventricular tachyarrhythmias
      and normal coronary arteriograms.

PMID- 14691032
TI  - A possible explanation of statistical interaction, with application to the
      effects of soluble thrombomodulin and soluble intercellular adhesion molecule-1
      on coronary heart disease.

PMID- 14691034
TI  - Muscle interstitial calcium during head-up tilt in humans.
AB  - BACKGROUND: During head-up tilt (HUT), peripheral vasoconstriction occurs. This
      response requires appropriate communication between the sympathetic nerve
      terminal and vascular smooth muscle cell in the neurovascular space. Both of
      these cell types require extracellular calcium ([Ca2+]o) for proper activation
      and function. We hypothesize that [Ca2+]o rises with tilt and in the process
      contributes to vasoconstriction. METHODS AND RESULTS: We used microdialysis
      techniques in the lower-limb skeletal muscle to measure [Ca2+]o changes in this
      space with HUT. [Ca2+]o was measured in 10 healthy subjects during HUT. We found
      a 62% increase in the dialysate [Ca2+] (0.223+/-0.018 to 0.353+/-0.028 mmol/L)
      with HUT. CONCLUSIONS: This result implies a significant increase in [Ca2+]o in
      the neurovascular space during HUT. This represents the first report of such in
      situ [Ca2+]o measurements in humans. This rise in [Ca2+]o may provide a mechanism
      for proper cell-cell interaction, helping to promote peripheral vasoconstriction
      during HUT. How this [Ca2+]o transient affects the nerve terminal, vascular
      smooth muscle cells, or both remains to be determined.

PMID- 14691035
TI  - Differences between mainstream and sidestream cigarette smoke extracts and
      nicotine in the activation of platelets under static and flow conditions.
AB  - BACKGROUND: Cigarette smoke is a primary risk factor for cardiovascular diseases.
      Enhanced function of the hemostatic system, in which platelets play a major role,
      is a significant underlying mechanism in cardiovascular disease and its
      progression. Epidemiological studies, complemented by physiological and
      biochemical data, show that cigarette smoke adversely affects platelet function,
      both in smokers and in nonsmokers exposed to sidestream smoke. METHODS AND
      RESULTS: The thrombogenic potential of platelets subjected to mainstream smoke
      extracts, sidestream extracts, and nicotine was measured in vitro under static
      and dynamic flow conditions. Platelet activation state was measured with a
      modified prothrombinase-based method. Mainstream and sidestream smoke extracts
      caused increased platelet activation. Although low-tar mainstream extracts
      activated platelets less than high-tar extracts, the sidestream extracts were
      almost equally potent. Modification of the filters of low-tar cigarettes, by
      blocking the air-bypass holes, raised activation rates by mainstream extracts to
      the level of high-tar extracts. Nicotine (50 nmol/L and 5 micromol/L) inhibited
      platelet activation under both flow and static conditions. CONCLUSIONS: Cigarette
      smoke extracts directly cause platelet activation but also markedly increase the
      susceptibility of platelets to activation by shear stress. In contrast, nicotine,
      although also a constituent of cigarette smoke, significantly reduces platelet
      susceptibility to shear stress.

PMID- 14691036
TI  - Chronic arterial responses to polymer-controlled paclitaxel-eluting stents:
      comparison with bare metal stents by serial intravascular ultrasound analyses:
      data from the randomized TAXUS-II trial.
AB  - BACKGROUND: Polymer-controlled paclitaxel-eluting stents have shown a pronounced
      reduction in neointimal hyperplasia compared with bare metal stents (BMS). The
      aim of this substudy was to evaluate local arterial responses through the use of
      serial quantitative intravascular ultrasound (IVUS) analyses in the TAXUS II
      trial. METHODS AND RESULTS: TAXUS II was a randomized, double-blind study with
      536 patients in 2 consecutive cohorts comparing slow-release (SR; 131 patients)
      and moderate-release (MR; 135 patients) paclitaxel-eluting stents with BMS (270
      patients). This IVUS substudy included patients treated with one study stent who
      underwent serial IVUS examination after the procedure and at 6-month follow-up
      (BMS, 152 patients; SR, 81; MR, 81). The analyzed stented segment (15 mm) was
      divided into 5 subsegments in which mean vessel area (VA), stent area (SA), lumen
      area (LA), intrastent neointimal hyperplasia area (NIHA), and peristent area (VA
      SA) were measured. NIHA was significantly reduced in SR (0.7+/-0.9 mm2, P<0.001)
      and MR (0.6+/-0.8 mm2, P<0.001) compared with BMS (1.9+/-1.5 mm2), with no
      differences between the two paclitaxel-eluting release formulations. Longitudinal
      distribution of neointimal hyperplasia throughout the paclitaxel-eluting stent
      was uniform. Neointimal growth was independent of peristent area at postprocedure
      examination in all groups. There were progressive increases in peristent area
      from BMS to SR to MR (0.5+/-1.7, 1.0+/-1.8, and 1.4+/-2.0 mm2, respectively;
      P<0.001). The increase in peristent area was directly correlated with increases
      in VA. CONCLUSIONS: Both SR and MR paclitaxel-eluting stents prevent neointimal
      formation to the same degree compared with BMS. However, the difference in
      peristent remodeling suggests a release-dependent effect between SR and MR.

PMID- 14691037
TI  - Unrestricted utilization of sirolimus-eluting stents compared with conventional
      bare stent implantation in the "real world": the Rapamycin-Eluting Stent
      Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry.
AB  - BACKGROUND: The effectiveness of sirolimus-eluting stents in unselected patients
      treated in the daily practice is currently unknown. METHODS AND RESULTS:
      Sirolimus-eluting stent implantation has been used as the default strategy for
      all percutaneous procedures in our hospital as part of the Rapamycin-Eluting
      Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. Consecutive
      patients with de novo lesions (n=508) treated exclusively with sirolimus-eluting
      stents (SES group) were compared with 450 patients who received bare stents in
      the period just before (pre-SES group). Patients in the SES group more frequently
      had multivessel disease, more type C lesions, received more stents, and had more
      bifurcation stenting. At 1 year, the cumulative rate of major adverse cardiac
      events (death, myocardial infarction, or target vessel revascularization) was
      9.7% in the SES group and 14.8% in the pre-SES group (hazard ratio [HR], 0.62
      [95% CI, 0.44 to 0.89]; P=0.008). The 1-year risk of clinically driven target
      vessel revascularization in the SES group and in the pre-SES group was 3.7%
      versus 10.9%, respectively (HR, 0.35 [95% CI, 0.21 to 0.57]; P<0.001).
      CONCLUSIONS: Unrestricted utilization of sirolimus-eluting stents in the "real
      world" is safe and effective in reducing both repeat revascularization and major
      adverse cardiac events at 1 year compared with bare stent implantation.

PMID- 14691038
TI  - Endothelin A receptor antagonism in experimental congestive heart failure results
      in augmentation of the renin-angiotensin system and sustained sodium retention.
AB  - BACKGROUND: While both the endothelin-1 (ET-1) and renin-angiotensin systems
      (RAS) are activated in congestive heart failure (CHF), the temporal sequence of
      this activation remains unclear. Understanding this pattern of neurohumoral
      activation may aid in understanding the significance of ET-1 in CHF and provide
      strategies for ET-1 antagonism. Although acute endothelin (ET) receptor
      antagonism improves systemic hemodynamics in CHF, clinical trials with chronic ET
      receptor antagonism report worsening CHF symptoms. METHODS AND RESULTS: In a
      canine model of progressive left ventricular dysfunction, we demonstrated
      activation of myocardial and plasma ET-1 without activation of the RAS during
      transition to overt CHF, suggesting that ET-1 contributes to this transition. We
      next evaluated the effects of chronic oral ET-A receptor antagonism on
      neurohumoral function, renal hemodynamics, and sodium excretion in pacing-induced
      CHF. After 7 days of treatment (n=7) with ET-A receptor antagonism (with
      LU135252), sodium excretion did not improve in treated versus untreated CHF
      (n=6). Furthermore, both plasma renin activity and plasma ET-1 increased with ET
      A receptor blockade. CONCLUSIONS: Activation of the myocardial and plasma ET-1
      systems precedes activation of the myocardial and plasma RAS in CHF. ET-A
      receptor antagonism in experimental CHF further activates the RAS without
      improving sodium excretion. These findings suggest an important role for ET-1 in
      the progression of CHF and a potential mechanism for the exacerbation of CHF
      symptoms observed in clinical trials with chronic ET receptor antagonism. Further
      studies with combined modulation of the ET and other neurohumoral systems in CHF
      are required.

PMID- 14691039
TI  - Physical training increases endothelial progenitor cells, inhibits neointima
      formation, and enhances angiogenesis.
AB  - BACKGROUND: The molecular mechanisms by which physical training improves
      peripheral and coronary artery disease are poorly understood. Bone marrow-derived
      endothelial progenitor cells (EPCs) are thought to exert beneficial effects on
      atherosclerosis, angiogenesis, and vascular repair. METHODS AND RESULTS: To study
      the effect of physical activity on the bone marrow, EPCs were quantified by
      fluorescence-activated cell sorter analysis in mice randomized to running wheels
      (5.1+/-0.8 km/d, n=12 to 16 per group) or no running wheel. Numbers of EPCs
      circulating in the peripheral blood of trained mice were enhanced to 267+/-19%,
      289+/-22%, and 280+/-25% of control levels after 7, 14, and 28 days,
      respectively, accompanied by a similar increase of EPCs in the bone marrow and
      EPCs expanded from spleen-derived mononuclear cells. eNOS-/- mice and wild-type
      mice treated with N(G)-nitro-l-arginine methyl ester showed lower EPC numbers at
      baseline and a significantly attenuated increase of EPC in response to physical
      activity. Exercise NO dependently increased serum levels of vascular endothelial
      growth factor and reduced the rate of apoptosis in spleen-derived EPCs. Running
      inhibited neointima formation after carotid artery injury by 22+/-2%.
      Neoangiogenesis, as assessed in a subcutaneous disc model, was increased by 41+/
      16% compared with controls. In patients with stable coronary artery disease
      (n=19), moderate exercise training for 28 days led to a significant increase in
      circulating EPCs and reduced EPC apoptosis. CONCLUSIONS: Physical activity
      increases the production and circulating numbers of EPCs via a partially NO
      dependent, antiapoptotic effect that could potentially underlie exercise-related
      beneficial effects on cardiovascular diseases.

PMID- 14691040
TI  - Stabilization of atherosclerotic plaques by blockade of macrophage migration
      inhibitory factor after vascular injury in apolipoprotein E-deficient mice.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF), a cytokine that
      controls cell-mediated inflammatory responses, is upregulated in atherogenesis;
      however, its functional contribution to lesion development has not been
      evaluated. METHODS AND RESULTS: We studied the role of MIF on neointima lesion
      formation after wire-induced injury of carotid arteries in apolipoprotein E
      deficient (apoE(-/-)) mice. Immunohistochemistry revealed that MIF expression was
      detectable in endothelial cells before injury and upregulated in smooth muscle
      cells (SMCs) 24 hours after endothelial denudation. Three weeks after injury, MIF
      was predominantly found in endothelial cells and macrophage-derived foam cells.
      Neutralizing MIF with a monoclonal antibody resulted in a marked reduction of
      neointimal macrophages and inhibited transformation of macrophages into foam
      cells. Conversely, the content of SMCs and of collagen in the neointima were
      increased, amounting to a slight but not significant reduction in neointima and
      media size after 3 weeks of MIF monoclonal antibody treatment. Notably, serum
      levels of the cytokines IL-2, IL-4, IL-6, IL-10, and tumor necrosis factor were
      increased in MIF monoclonal antibody-treated mice. In vitro flow assays revealed
      that MIF pretreatment of aortic endothelium enhanced monocyte recruitment and
      that the monocyte arrest induced by oxidized LDL is mediated by endothelial MIF,
      as shown by monoclonal antibody inhibition. CONCLUSIONS: Inhibition of MIF
      resulted in a shift in the cellular composition of neointimal plaques toward a
      stabilized phenotype with reduced macrophage/foam cell content and increased SMC
      content. This might be attributable to a reduction of monocyte recruitment
      mediated by endothelial MIF.

PMID- 14691041
TI  - Adrenomedullin infusion attenuates myocardial ischemia/reperfusion injury through
      the phosphatidylinositol 3-kinase/Akt-dependent pathway.
AB  - BACKGROUND: Infusion of adrenomedullin (AM) has beneficial hemodynamic effects in
      patients with heart failure. However, the effect of AM on myocardial
      ischemia/reperfusion remains unknown. METHODS AND RESULTS: Male Sprague-Dawley
      rats were exposed to a 30-minute period of ischemia induced by ligation of the
      left coronary artery. They were randomized to receive AM, AM plus wortmannin (a
      phosphatidylinositol 3-kinase [PI3K] inhibitor), or saline for 60 minutes after
      coronary ligation. Hemodynamics and infarct size were examined 24 hours after
      reperfusion. Myocardial apoptosis was also examined 6 hours after reperfusion.
      The effect of AM on Akt phosphorylation in cardiac tissues was examined by
      Western blotting. Intravenous administration of AM significantly reduced
      myocardial infarct size (28+/-4% to 16+/-1%, P<0.01), left ventricular end
      diastolic pressure (19+/-2 to 8+/-2 mm Hg, P<0.05), and myocardial apoptotic
      death (19+/-2% to 9+/-4%, P<0.05). Western blot analysis showed that AM infusion
      accelerated Akt phosphorylation in cardiac tissues and that pretreatment with
      wortmannin significantly attenuated AM-induced Akt phosphorylation. Moreover,
      pretreatment with wortmannin abolished the beneficial effects of AM: a reduction
      of infarct size, a decrease in left ventricular end-diastolic pressure, and
      inhibition of myocardial apoptosis after ischemia/reperfusion. CONCLUSIONS: Short
      term infusion of AM significantly attenuated myocardial ischemia/reperfusion
      injury. These cardioprotective effects are attributed mainly to antiapoptotic
      effects of AM via a PI3K/Akt-dependent pathway.

PMID- 14691042
TI  - Focal atrial tachycardia: new insight from noncontact mapping and catheter
      ablation.
AB  - BACKGROUND: This study investigated the electrophysiologic characteristics,
      atrial activation pattern, and effects of radiofrequency (RF) catheter ablation
      guided by noncontact mapping system in patients with focal atrial tachycardia
      (AT). METHODS AND RESULTS: In 13 patients with 14 focal ATs, noncontact mapping
      system was used to map and guide ablation of AT. AT origins were in the crista
      terminalis (n=8), right atrial (RA) free wall (n=3), Koch triangle (n=1),
      anterior portion of RA-inferior vena cava junction (n=1), and superior portion of
      tricuspid annulus (n=1); breakout sites were in the crista terminalis (n=5), RA
      free wall (n=5), middle cavotricuspid isthmus (n=2), and RA-superior vena cava
      junction (n=2). ATs arose from the focal origins (11 ATs inside or at the border
      of low-voltage zone), with preferential conduction, breakout, and spread to the
      whole atrium. After applications of RF energy on the earliest activation site or
      the proximal portion of preferential conduction from AT origin, 13 ATs were
      eliminated without complication. During the follow-up period (8+/-5 months), 11
      (91.7%) of the 12 patients with successful ablation were free of focal ATs.
      CONCLUSIONS: Focal AT originates from a small area and spreads out to the whole
      atrium through a preferential conduction. Application of RF energy guided by
      noncontact mapping system was effective and safe in eliminating focal AT.

PMID- 14691043
TI  - Impaired renal clearance explains elevated troponin T fragments in hemodialysis
      patients.
AB  - BACKGROUND: Patients with severe renal dysfunction often have unexplained
      elevated serum concentrations of cardiac troponin T (cTnT). We investigated
      whether in vivo fragmentation of cTnT could explain these increases. METHODS AND
      RESULTS: cTnT, creatine kinase isoenzyme MB, and myoglobin serum concentrations
      were measured in all 63 dialysis patients of our in-hospital dialysis department.
      A highly sensitive immunoprecipitation assay, followed by electrophoresis and
      Western blotting, was used to extract and concentrate cTnT and its possible
      fragments from serum of these 63 hemodialysis patients. Although creatine kinase
      isoenzyme MB values excluded recent ischemic myocardial events in 55 of the 63
      cases, cTnT fragments ranging in size from 8 to 25 kDa were present in the serum
      samples of all dialysis patients. CONCLUSIONS: cTnT is fragmented into molecules
      small enough to be cleared by the kidneys of healthy subjects. Impaired renal
      function causes accumulation of these cTnT fragments and is very likely the cause
      of the unexplained elevations of serum cTnT found in patients with severe renal
      failure.

PMID- 14691044
TI  - Unusual effects of a QT-prolonging drug, arsenic trioxide, on cardiac potassium
      currents.
AB  - BACKGROUND: Cases of QT prolongation, torsades de pointes, and sudden death have
      been reported with arsenic trioxide (As2O3), a highly effective agent for acute
      promyelocytic leukemia. In this study, we evaluated the effects of As2O3 on
      repolarizing cardiac ion currents. METHODS AND RESULTS: In HERG- or KCNQ1+KCNE1
      transfected CHO cells (n=32; total), As2O3 caused concentration-dependent block
      of both IKr and IKs, with an IC50 for tail current block of 0.14+/-0.01
      micromol/L for IKr and 1.13+/-0.06 micromol/L for IKs. In contrast to other QT
      prolonging drugs, As2O3 also activated a time-independent current that additional
      experiments identified as IK-ATP. CONCLUSIONS: As2O3 blocks both IKr and IKs at
      clinically relevant concentrations. On the other hand, it also activates IK-ATP,
      which maintains normal repolarization. We infer that variability in the extent of
      QT interval prolongation and onset of ventricular arrhythmias during arsenic
      therapy represents competing effects to block and activate multiple repolarizing
      potassium currents.

PMID- 14691045
TI  - Detection of calcified and noncalcified coronary atherosclerotic plaque by
      contrast-enhanced, submillimeter multidetector spiral computed tomography: a
      segment-based comparison with intravascular ultrasound.
AB  - BACKGROUND: We investigated the ability of multidetector spiral computed
      tomography (MDCT) to detect atherosclerotic plaque in nonstenotic coronary
      arteries. METHODS AND RESULTS: In 22 patients without significant coronary
      stenoses, contrast-enhanced MDCT (0.75-mm collimation, 420-ms rotation) and
      intravascular ultrasound (IVUS) of one coronary artery were performed. A total of
      83 coronary segments were imaged by IVUS (left main, 19; left anterior
      descending, 51; left circumflex, 4; right coronary, 9). MDCT data sets were
      evaluated for the presence and volume of plaque in the coronary artery segments.
      Results were compared with IVUS in a blinded fashion. For the detection of
      segments with any plaque, MDCT had a sensitivity of 82% (41 of 50) and
      specificity of 88% (29 of 33). For calcified plaque, sensitivity was 94% (33 of
      36) and specificity 94% (45 of 47). Coronary segments containing noncalcified
      plaque were detected with a sensitivity of 78% (35 of 45) and specificity of 87%
      (33 of 38), but presence of exclusively noncalcified plaque was detected with
      only 53% sensitivity (8 of 15). If analysis was limited to the 41 proximal
      segments (segments 1, 5, 6, and 11 according to American Heart Association
      classification), sensitivity and specificity were 92% and 88% for any plaque, 95%
      and 91% for calcified plaque, and 91% and 89% for noncalcified plaque. MDCT
      substantially underestimated plaque volume per segment as compared with IVUS
      (24+/-35 mm3 versus 43+/-60 mm3, P<0.001). CONCLUSIONS: The results indicate the
      potential of MDCT to detect coronary atherosclerotic plaque in patients without
      significant coronary stenoses. However, further improvements in image quality
      will be necessary to achieve reliable assessment, especially of noncalcified
      plaque throughout the coronary tree.

PMID- 14691046
TI  - Protein kinase C modulation of the regulation of sarcoplasmic reticular function
      by protein kinase A-mediated phospholamban phosphorylation in diabetic rats.
AB  - 1. The goal of this study was to elucidate the possible mechanisms by which
      protein kinase A (PKA)-mediated regulation of the sarcoplasmic reticulum (SR) via
      phospholambin protein phosphorylation is functionally impaired in streptozotocin
      induced diabetic rats. 2. Phospholamban (PLB) protein and mRNA levels were 1.3
      fold higher in diabetic than in control hearts, while protein expression of
      cardiac SR Ca(2+)-ATPase (SERCA2a) was unchanged. 3. Basal and isoprenaline
      stimulated phosphorylation of PLB at Ser(16) or Thr(17) was unchanged in diabetic
      hearts. However, stronger immunoreactivity was observed at the basal level in
      diabetic hearts when antiphosphoserine antibody was used. 4. Basal (32)P
      incorporation into PLB was significantly higher in diabetic than in control SR
      vesicles, but the extent of the PKA-mediated increase in PLB phosphorylation was
      the same in the two groups of vesicles. 5. Stimulation of Ca(2+) uptake by PKA
      catalyzed PLB phosphorylation was weaker in diabetic than in control SR vesicles.
      The PKA-induced increase in Ca(2+) uptake was attenuated when control SR vesicles
      were preincubated with protein kinase C (PKC). 6. PKC activities were increased
      by more than two-fold in the membranous fractions from diabetic hearts in
      comparison with control values, regardless of whether Ca(2+) was present. This
      was associated with increases in the protein content of PKCdelta, PKCeta,
      PKCiota, and PKClambda in diabetic membranous fractions. 7. The changes observed
      in diabetic rats were reversed by insulin therapy. 8. These results suggest that
      PKA-dependent phosphorylation may incompletely counteract the function of PLB as
      an inhibitor of SERCA2a activity in diabetes in which PKC expression and activity
      are enhanced.

PMID- 14691047
TI  - Endosome sorting of beta 2-adrenoceptors is GRK5 independent.
AB  - 1. We have investigated the role of G protein-coupled receptor kinase 5 (GRK5) in
      the regulation of endosome sorting of human beta(2)-adrenoceptors. 2. Expressing
      GRK5 at a high level significantly increased the extent of internalization of
      wild-type beta(2)-adrenoceptors and of an internalization-defective mutant
      receptor, and increased receptor phosphorylation at serines 355 and 356 in the
      cytoplasmic tail. 3. Overexpressing GRK5 did not alter beta(2)-adrenoceptor
      recycling as assessed by immunofluorescence microscopy and radioligand binding
      assays nor was there any change in receptor downregulation. 4. These data
      indicate that GRK5 does not regulate the sorting of beta(2)-adrenoceptors in the
      endocytic pathway.

PMID- 14691048
TI  - Platelet-activating factor increases pH(i) in bovine neutrophils through the PI3K
      ERK1/2 pathway.
AB  - 1. Platelet-activating factor (PAF) is known to stimulate a variety of neutrophil
      activities, including chemotaxis, phagocytosis, degranulation, reactive oxygen
      species production and intracellular pH increase. The purpose of this study was
      to investigate the effect of PAF on pH((i)), specifically if these changes in pH
      are the result of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated
      protein kinase (MAPK) pathway activation in bovine neutrophils. 2. PAF caused
      intracellular alkalinization in 2',7'-bis-(2-carboxyethyl)-5-(and-6)
      carboxyfluorescein acetoxymethyl ester-loaded bovine neutrophils. This phenomenon
      seems to be mediated by amiloride-sensitive Na(+)/H(+) exchange, and is inhibited
      by WEB2086 (a selective PAF receptor antagonist), genistein (a tyrosine kinase
      inhibitor), wortmannin and LY294002 (PI3K inhibitors), and PD98059 and UO126 (MEK
      inhibitors). 3. PAF 100 nm induced an increase in tyrosine phosphorylation of
      proteins 62, 44 and 21 kDa with a maximum response at 2 min of incubation. 4.
      Unlike human neutrophils, bovine neutrophils are strongly stimulated by PAF via
      phosphorylation of ERK1/2 (extracellular-signal-regulated protein kinase) with an
      EC(50) of 30 and 13 nm, respectively. 5. PAF MAPK activation was also inhibited
      by WEB2086, pertussis toxin (PTX), genistein, wortmannin, LY294002, PD98059 and
      UO126 in bovine neutrophils. The ERK1/2 activation is dependent on PI3K pathway,
      because protein kinase B was phosphorylated by PAF and inhibited by wortmannin
      and LY294002, but not by U0126. 6. Our results suggest that PAF induces
      intracellular alkalinization via PI3K-MAPK activation. This effect is upstream
      regulated by PAF receptor, PTX-sensitive G protein, tyrosine kinase, PI3K and
      MEK1/2 in bovine neutrophils.

PMID- 14691049
TI  - Chronic treatment of male rats with daidzein and 17 beta-oestradiol induces the
      contribution of EDHF to endothelium-dependent relaxation.
AB  - 1. We investigated the effect of chronic (7 days) treatment of male rats with the
      isoflavone daidzein (0.2 mg kg(-1) sc per day) or 17beta-oestradiol (0.1 mg kg(
      1) sc per day) on the contribution of nitric oxide (NO), prostaglandins and
      endothelium-derived hyperpolarising factor (EDHF) to endothelium-dependent
      relaxation of isolated aortic rings. 2. The sensitivity and maximum relaxation to
      acetylcholine (ACh) were significantly greater in aortic rings from rats treated
      with daidzein or 17beta-oestradiol, in comparison to vehicle-treated rats.
      Inhibition of nitric oxide synthase with N-nitro-l-arginine (l-NOARG) abolished
      ACh-induced relaxation in the aortae from vehicle-treated rats, but only
      attenuated relaxation in aortae from daidzein or 17beta-oestradiol-treated rats.
      The presence of haemoglobin in addition to l-NOARG did not cause any further
      inhibition of relaxation. 3. The cyclooxygenase inhibitor indomethacin had no
      effect on endothelium-dependent relaxation in aortae from any treatment group.
      Charybdotoxin (ChTX), which blocks large-conductance calcium-activated potassium
      channels (BK(Ca)) and intermediate-conductance calcium-activated potassium
      channels (IK(Ca)), plus apamin, which blocks small-conductance calcium-activated
      potassium channels (SK(Ca)), but not iberiotoxin, which only blocks BK(Ca),
      attenuated endothelium-dependent relaxation of aortae from daidzein or 17beta
      oestradiol-treated rats. Blockade of K(Ca) channels had no effect on the
      responses to ACh in aortae from vehicle-treated rats. In aortae from daidzein- or
      17beta-oestradiol-treated rats, endothelium-dependent relaxation was also
      attenuated by inhibition of cytochrome P450 (CYP450) epoxygenase with 6-(2
      propargylloxyphenyl)hexanoic acid (PPOH) or inhibition of K(IR) channels and
      Na(+)/K(+)-ATPase with barium and oubain, respectively. 4. This study
      demonstrates that endothelium-dependent relaxation of male rat aorta is normally
      entirely mediated by NO, whereas treatment with daidzein or 17beta-oestradiol
      stimulates a contribution from a non-NO, nonprostaglandin factor acting through
      the opening of SK(Ca) and IK(Ca) channels, and involving activation of Na/K
      ATPase, K(IR) and CYP450 epoxygenase. This pattern of sensitivity to the tested
      inhibitors is consistent with the contribution of EDHF to relaxation. Thus, EDHF
      contributes to the enhanced endothelium-dependent relaxation that is observed
      after chronic treatment with the phytoestrogen daidzein or with 17beta
      oestradiol.

PMID- 14691050
TI  - Coupling of boswellic acid-induced Ca2+ mobilisation and MAPK activation to lipid
      metabolism and peroxide formation in human leucocytes.
AB  - 1. We have previously shown that 11-keto boswellic acids (11-keto-BAs), the
      active principles of Boswellia serrata gum resins, activate p38 MAPK and
      p42/44(MAPK) and stimulate Ca(2+) mobilisation in human polymorphonuclear
      leucocytes (PMNL). 2. In this study, we attempted to connect the activation of
      MAPK and mobilisation of Ca(2+) to functional responses of PMNL, including the
      formation of reactive oxygen species (ROS), release of arachidonic acid (AA), and
      leukotriene (LT) biosynthesis. 3. We found that, in PMNL, 11-keto-BAs stimulate
      the formation of ROS and cause release of AA as well as its transformation to LTs
      via 5-lipoxygenase. 4. Based on inhibitor studies, 11-keto-BA-induced ROS
      formation is Ca(2+)-dependent and is mediated by NADPH oxidase involving PI 3-K
      and p42/44(MAPK) signalling pathways. Also, the release of AA depends on Ca(2+)
      and p42/44(MAPK), whereas the pathways stimulating 5-LO are not readily apparent.
      5. Pertussis toxin, which inactivates G(i/0) protein subunits, prevents MAPK
      activation and Ca(2+) mobilisation induced by 11-keto-BAs, implying the
      involvement of a G(i/0) protein in BA signalling. 6. Expanding studies on
      differentiated haematopoietic cell lines (HL60, Mono Mac 6, BL41-E-95-A)
      demonstrate that the ability of BAs to activate MAPK and to mobilise Ca(2+) may
      depend on the cell type or the differentiation status. 7. In summary, we conclude
      that BAs act via G(i/0) protein(s) stimulating signalling pathways that control
      functional leucocyte responses, in a similar way as chemoattractants, that is, N
      formyl-methionyl-leucyl-phenylalanine or platelet-activating factor.

PMID- 14691051
TI  - Antitussive activity of sigma-1 receptor agonists in the guinea-pig.
AB  - 1. Current antitussive medications have limited efficacy and often contain the
      opiate-like agent dextromethorphan (DEX). The mechanism whereby DEX inhibits
      cough is ill defined. DEX displays affinity at both NMDA and sigma receptors,
      suggesting that the antitussive activity may involve central or peripheral
      activity at either of these receptors. This study examined and compared the
      antitussive activity of DEX and various putative sigma receptor agonists in the
      guinea-pig citric-acid cough model. 2. Intraperitoneal (i.p.) administration of
      DEX (30 mg kg(-1)) and the sigma-1 agonists SKF-10,047 (1-5 mg kg(-1)), Pre-084
      (5 mg kg(-1)), and carbetapentane (1-5 mg kg(-1)) inhibited citric-acid-induced
      cough in guinea-pigs. Intraperitoneal administration of a sigma-1 antagonist, BD
      1047 (1-5 mg kg(-1)), reversed the inhibition of cough elicited by SKF-10,047. In
      addition, two structurally dissimilar sigma agonists SKF-10,047 (1 mg ml(-1)) and
      Pre-084 (1 mg ml(-1)) inhibited cough when administered by aerosol. 3.
      Aerosolized BD 1047 (1 mg ml(-1), 30 min) prevented the antitussive action of SKF
      10,047 (5 mg kg(-1)) or DEX (30 mg kg(-1)) given by i.p. administration and,
      likewise, i.p. administration of BD 1047 (5 mg kg(-1)) prevented the antitussive
      action of SKF-10,047 given by aerosol (1 mg ml(-1)). 4. These results therefore
      support the argument that antitussive effects of DEX may be mediated via sigma
      receptors, since both systemic and aerosol administration of sigma-1 receptor
      agonists inhibit citric-acid-induced cough in guinea-pigs. While significant
      systemic exposure is possible with aerosol administration, the very low doses
      administered (estimated <0.3 mg kg(-1)) suggest that there may be a peripheral
      component to the antitussive effect.

PMID- 14691053
TI  - Oleamide: a member of the endocannabinoid family?
AB  - The fatty acid amide class of compounds, which include the endocannabinoid
      anandamide and the sleep-inducing compound oleamide, have been shown in vitro to
      have a multiplicity of actions upon different neurochemical systems. In the
      present issue of this journal, Leggett et al present data indicating that
      oleamide functionally activates CB(1) cannabinoid receptors in vitro. The
      significance of their finding is discussed in this commentary.

PMID- 14691052
TI  - Membrane type-1 matrix metalloproteinase stimulates tumour cell-induced platelet
      aggregation: role of receptor glycoproteins.
AB  - 1. Matrix metalloproteinase-2 (MMP-2) plays a role in agonist- and tumour cell
      induced platelet aggregation (TCIPA). 2. MMP-2 is synthesized as a proenzyme and
      is activated at the cell surface by membrane type-1 matrix metalloproteinase (MT1
      MMP, MMP-14). 3. The significance of tumour cell-associated MT1-MMP for TCIPA was
      investigated using human breast carcinoma MCF7 cells stably coexpressing the
      integrin alphavbeta3 with MT1-MMP, cells expressing alphavbeta3 alone and mock
      transfected cells. 4. Western blot and zymography confirmed that alphavbeta3/MT1
      MMP cells expressed MT1-MMP and efficiently processed proMMP-2 to MMP-2. 5.
      Aggregometry, phase-contrast and transmission electron microscopy and flow
      cytometry were used to characterize TCIPA induced by MCF7 cell lines. 6. The
      aggregating potency of cells was: alphavbeta3/MT1-MMP >alphavbeta3=mock cells, as
      shown by aggregometry and phase-contrast microscopy. 7. Electron microscopy
      revealed close, membrane-membrane interactions between activated platelets and
      alphavbeta3/MT1-MMP cells during TCIPA. 8. Inhibition of MMP-2 with the
      neutralizing anti-MMP-2 antibody (5 microg ml(-1)) and o-phenanthroline (100
      microm) reduced aggregation induced by alphavbeta3/MT1-MMP cells. 9. TCIPA
      induced by alphavbeta3/MT1-MMP cells was also reduced by inhibiting the
      generation and actions of ADP with apyrase (250 microg ml(-1)) and 2-methylthio
      AMP (2-MeSAMP) (30 microm), but not N(6)-methyl-2'-deoxyadenosine-3',5'
      bisphosphate (MRS2179) (30 microm). 10. Flow cytometry demonstrated that TCIPA
      enhanced expression of glycoprotein (GP) Ib and IIb/IIIa receptors not only on
      platelets but also on breast cancer cells. 11. Thus, (a) human breast carcinoma
      cell surface-associated MT1-MMP, via activating proMMP-2, stimulates TCIPA; (b)
      ADP amplifies the effects of MMPs via stimulation of P2Y(12) receptors and (c)
      both tumour- and platelet-derived GPIb and GPIIb/IIIa are involved in the
      aggregatory effects of MT1-MMP.

PMID- 14691054
TI  - Calcineurin-independent inhibition of mitochondrial Ca2+ uptake by cyclosporin A.
AB  - 1. Cyclosporin A (CsA) is a widely used compound because of its potent
      immunosupressive properties, derived mainly from the inhibition of calcineurin,
      and also because of its ability to block the mitochondrial permeability
      transition pore (PTP). This second effect has been involved in the protection
      against apoptosis mediated by release of mitochondrial factors. We show here that
      CsA (1-10 microm) has an additional effect on Ca(2+) homeostasis in mitochondria
      that cannot be attributed to inhibition of PTP. 2. By measuring specifically
      mitochondrial [Ca(2+)] with targeted aequorin, we show that CsA inhibited Ca(2+)
      entry into mitochondria both in intact and in permeabilized cells, and this
      effect was stronger when Ca(2+) entry was triggered by low cytosolic [Ca(2+)],
      below 5 microm. 3. Inhibition of mitochondrial Ca(2+) uptake required micromolar
      concentrations of CsA and was not mimicked by other inhibitors of calcineurin
      such as FK-506 or cypermethrin, nor by a different inhibitor of the PTP,
      bongkrekic acid. 4. CsA blocked the increase in mitochondrial Ca(2+) uptake rate
      induced by the mitochondrial Ca(2+) uniporter activator SB202190. 5. Our results
      suggest that CsA inhibits Ca(2+) entry through the Ca(2+) uniporter by a
      mechanism independent of the inhibition of PTP or calcineurin. This effect may
      contribute to reduce depolarization and Ca(2+) overloading in mitochondria after
      cell stimulation, and thus cooperate with the direct inhibition of PTP to prevent
      apoptosis.

PMID- 14691055
TI  - Characterisation of the binding of [3H]-SB-674042, a novel nonpeptide antagonist,
      to the human orexin-1 receptor.
AB  - 1. This study characterises the binding of a novel nonpeptide antagonist
      radioligand, [(3)H]SB-674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1
      ((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone), to the
      human orexin-1 (OX(1)) receptor stably expressed in Chinese hamster ovary (CHO)
      cells in both a whole cell assay and in a cell membrane-based scintillation
      proximity assay (SPA) format. 2. Specific binding of [(3)H]SB-674042 was
      saturable in both whole cell and membrane formats. Analyses suggested a single
      high-affinity site, with K(d) values of 3.76+/-0.45 and 5.03+/-0.31 nm, and
      corresponding B(max) values of 30.8+/-1.8 and 34.4+/-2.0 pmol mg protein(-1), in
      whole cell and membrane formats, respectively. Kinetic studies yielded similar
      K(d) values. 3. Competition studies in whole cells revealed that the native
      orexin peptides display a low affinity for the OX(1) receptor, with orexin-A
      displaying a approximately five-fold higher affinity than orexin-B (K(i) values
      of 318+/-158 and 1516+/-597 nm, respectively). 4. SB-334867, SB-408124 (1-(6,8
      difluoro-2-methyl-quinolin-4-yl)-3-(4-dimethylamino-phenyl)-urea) and SB-410220
      (1-(5,8-difluoro-quinolin-4-yl)-3-(4-dimethylamino-phenyl)-urea) all displayed
      high affinity for the OX(1) receptor in both whole cell (K(i) values 99+/-18,
      57+/-8.3 and 19+/-4.5 nm, respectively) and membrane (K(i) values 38+/-3.6, 27+/
      4.1 and 4.5+/-0.2 nm, respectively) formats. 5. Calcium mobilisation studies
      showed that SB-334867, SB-408124 and SB-410220 are all functional antagonists of
      the OX(1) receptor, with potencies in line with their affinities, as measured in
      the radioligand binding assays, and with approximately 50-fold selectivity over
      the orexin-2 receptor. 6. These studies indicate that [(3)H]SB-674042 is a
      specific, high-affinity radioligand for the OX(1) receptor. The availability of
      this radioligand will be a valuable tool with which to investigate the
      physiological functions of OX(1) receptors.

PMID- 14691056
TI  - Minoxidil opens mitochondrial K(ATP) channels and confers cardioprotection.
AB  - 1. ATP-sensitive potassium channel in the mitochondrial inner membrane
      (mitoK(ATP) channel) rather than in the sarcolemma (sarcK(ATP) channel) appears
      to play an important role in cardioprotection. We examined the effect of
      minoxidil, a potent antihypertensive agent and hair growth stimulator, on
      sarcK(ATP) and mitoK(ATP) channels in guinea-pig ventricular myocytes. 2.
      Minoxidil activated a glybenclamide-sensitive sarcK(ATP) channel current in the
      whole-cell recording mode with an EC(50) of 182.6 microm. Minoxidil reversibly
      increased the flavoprotein oxidation, an index of mitoK(ATP) channel activity, in
      a concentration-dependent manner. The EC(50) for mitoK(ATP) channel activation
      was estimated to be 7.3 microm; this value was notably approximately 25-fold
      lower than that for sarcK(ATP) channel activation. 3. Minoxidil (10 microm)
      significantly attenuated the ouabain-induced increase of mitochondrial Ca(2+)
      concentration, which was measured by loading cells with rhod-2 fluorescence.
      Furthermore, pretreatment with minoxidil (10 microm) before 20-min no-flow
      ischaemia significantly improved the recovery of developed tension measured after
      60 min of reperfusion in coronary perfused guinea-pig ventricular muscles. These
      cardioprotective effects of minoxidil were completely abolished by the mitoK(ATP)
      channel blocker 5-hydroxydecanoate (500 microm). 4. Our results indicate that
      minoxidil exerts a direct cardioprotective effect on heart muscle cells, an
      effect mediated by the selective activation of mitoK(ATP) channels.

PMID- 14691057
TI  - Effects of chloride channel blockers on hypotonicity-induced contractions of the
      rat trachea.
AB  - 1. We have investigated the inhibitory effects of blockers of volume-activated
      (Cl(vol)) and calcium-activated (Cl(Ca)) chloride channels on hypotonic solution
      (HS)-induced contractions of rat trachea, comparing their effects with those of
      the voltage-dependent calcium channel (VDCC) blocker nifedpine. 2. HS elicited
      large, stable contractions that were partially dependent on the cellular chloride
      gradient; a reduction to 41.45+/-7.71% of the control response was obtained when
      extracellular chloride was removed. In addition, HS-induced responses were
      reduced to 26.8+/-5.6% of the control by 1 microm nifedipine, and abolished under
      calcium-free conditions, indicating a substantial requirement for extracellular
      calcium entry, principally via VDCCs. 3. The established Cl(vol) blockers
      tamoxifen (</=10 microm) and 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid
      (1-100 microm), at concentrations previously reported to inhibit Cl(vol) in
      smooth muscle, did not significantly inhibit HS-induced contractions. 4. In
      contrast, the recognized Cl(Ca) blocker niflumic acid (NFA; 1-100 microm)
      produced a reversible, concentration-dependent inhibition of HS responses, with a
      reduction to 36.6+/-6.4% of control contractions at the highest concentration.
      The mixed Cl(vol) and Cl(Ca) blocker, 5-nitro 2-(3-phenylpropylamine) benzoic
      acid (NPPB; 10-100 microm) also elicited concentration-related inhibition of HS
      induced contractions, producing a decrease to 35.9+/-11.3% of the control at 100
      microm. 5. Our results show that HS induces reversible, chloride-dependent
      contractions of rat isolated trachea that were inhibited by NFA and NPPB, while
      exhibiting little sensitivity to recognized blockers of Cl(vol). The data support
      the possibility that opening of calcium-activated chloride channels under
      hypotonic conditions in respiratory smooth muscle may ultimately lead to VDCC
      mediated calcium entry and contraction.

PMID- 14691059
TI  - Visual exploration behaviour during clock reading in Alzheimer's disease.
AB  - Eye movement behaviour during visual exploration of 24 patients with probable
      Alzheimer's disease and 24 age-matched controls was compared in a clock reading
      task. Controls were found to focus exploration on distinct areas at the end of
      each clock hand. The sum of these two areas of highest fixation density was
      defined as the informative region of interest (ROI). In Alzheimer's disease
      patients, visual exploration was less focused, with fewer fixations inside the
      ROI, and the time until the first fixation was inside the ROI was significantly
      delayed. Changes of fixation distribution correlated significantly with the
      ability to read the clock correctly, but did not correlate with dementia
      severity. In Alzheimer's disease patients, fixations were longer and saccade
      amplitudes were smaller. The altered visual exploration in Alzheimer's disease
      might be related to parietal dysfunction or to an imbalance between a degraded
      occipito-parietal and relatively preserved occipito-temporal visual network.

PMID- 14691060
TI  - Subthalamic nucleus stimulation modulates motor cortex oscillatory activity in
      Parkinson's disease.
AB  - In Parkinson's disease, impaired motor preparation has been related to an
      increased latency in the appearance of movement-related desynchronization (MRD)
      throughout the contralateral primary sensorimotor (PSM) cortex. Internal globus
      pallidus (GPi) stimulation improved movement desynchronization over the PSM
      cortex during movement execution but failed to improve impaired motor
      preparation. PET studies indicate that subthalamic nucleus (STN) stimulation
      partly reverses the abnormal premotor pattern of brain activation during
      movement. By monitoring MRD, we aimed to assess changes in premotor and PSM
      cortex oscillatory activity induced by bilateral STN stimulation and to compare
      these changes with those induced by l-dopa. Ten Parkinson's disease patients and
      a group of healthy, age-matched controls performed self-paced wrist flexions in
      each of four conditions: without either stimulation or l-dopa (the 'off'
      condition), with stimulation and without l-dopa (On Stim), with l-dopa and
      without stimulation ('on drug'), and with both stimulation and l-dopa (On Both).
      Compared with the Off condition, in both the On Stim and the On Drug condition
      the Unified Parkinson's Disease Rating Scale (UPDRS) III score decreased by about
      60% and in the On Both condition it decreased by 80%. The desynchronization
      latency over central regions contralateral to movement and the movement
      desynchronization over bilateral central regions were significantly increased by
      stimulation and by l-dopa, with a maximal effect when the two were associated.
      Furthermore, desynchronization latency significantly decreased over bilateral
      frontocentral regions in the three treatment conditions compared with the Off
      condition. In Parkinson's disease, STN stimulation may induce a change in
      abnormal cortical oscillatory activity patterns (similar to that produced by l
      dopa) by decreasing the abnormal spreading of desynchronization over
      frontocentral regions and increasing PSM cortex activity during movement
      preparation and execution, with a correlated improvement in bradykinesia.
      Parkinsonians under treatment displayed a desynchronization pattern close to that
      seen in healthy, age-matched controls, although central latencies remained
      shorter. The study indicates that it is possible to influence cortical reactivity
      related to the planning and execution of voluntary movement through the basal
      ganglia, and furthermore that the oscillatory activity of the PSM cortex (in
      addition to that of premotor areas) could be of major importance in the control
      of movement-associated, neural activity in Parkinson's disease.

PMID- 14691058
TI  - Topiramate hyperpolarizes and modulates the slow poststimulus AHP of rat
      olfactory cortical neurones in vitro.
AB  - 1. The effects of the novel antiepileptic drug topiramate (TPM) were investigated
      in rat olfactory cortex neurones in vitro using a current/voltage clamp
      technique. 2. In 80% of recorded cells, bath application of TPM (20 microm)
      reversibly hyperpolarized and inhibited neuronal repetitive firing by inducing a
      slow outward membrane current, accompanied by a conductance increase. The
      response was reproducible after washout, and was most likely carried largely by
      K(+) ions, although other ionic conductances may also have contributed. 3. In 90%
      of cells, TPM (20 microm) also enhanced and prolonged the slow (Ca(2+)-dependent)
      poststimulus afterhyperpolarization (sAHP) and underlying slow outward tail
      current (sI(AHP)). This effect was due to a selective enhancement/prolongation of
      an underlying L-type Ca(2+) current that was blocked by nifedipine (20 microm);
      the TPM response was unlikely to involve an interaction at PKA-dependent
      phosphorylation sites. 4. The carbonic anhydrase (CA) inhibitor acetazolamide
      (ACTZ, 20 microm) and the poorly membrane permeant inhibitor benzolamide (BZ, 50
      microm) both mimicked the membrane effects of TPM, in generating a slow
      hyperpolarization (slow outward current under voltage clamp) and sAHP
      enhancement. ACTZ and BZ occluded the effects of TPM in generating the outward
      current response, but were additive in producing the sAHP modulatory effect,
      suggesting different underlying response mechanisms. 5. In bicarbonate/CO(2)
      free, HEPES-buffered medium, all the membrane effects of TPM and ACTZ were
      reproducible, therefore not dependent on CA inhibition. 6. We propose that both
      novel effects of TPM and ACTZ exerted on cortical neurones may contribute towards
      their clinical effectiveness as anticonvulsants.

PMID- 14691061
TI  - Neurophysiological factors in human information processing capacity.
AB  - What determines how well an individual can manage the complexity of information
      processing demands when several tasks have to be executed simultaneously? Various
      theoretical frameworks address the mechanisms of information processing and the
      changes that take place when processes become automated, and brain regions
      involved in various types of information processing have been identified, as well
      as sequences of events in the brain. The neurophysiological substrate of human
      information processing capacity, i.e. the amount that can be processed
      simultaneously, is, however, unresolved, as is the basis of inter-individual
      variability in capacity. Automatization of cognitive functions is known to
      increase capacity to process additional tasks, but behavioural indices of
      automatization are poor predictors of processing capacity in individuals.
      Automatization also leads to a decline of brain activity in the working memory
      system. In this study, we test the hypothesis that processing capacity is closely
      related to the way that the brain adjusts to practice of a single cognitive task,
      i.e. to the changes in neuronal activity that accompany automatization as
      measured with functional MRI (fMRI). Using a task that taxes the working memory
      system, and is sensitive to automatization, performance improved while activity
      in the network declined, as expected. The key finding is that the magnitude of
      automatization-induced reduction of activity in this system was a strong
      predictor for the ability to perform two different working memory tasks
      simultaneously (after scanning). It explained 60% of the variation in information
      processing capacity across individuals. In contrast, the behavioural measures of
      automatization did not predict this. We postulate that automatization involves at
      least two partially independent neurophysiological mechanisms, i.e. (i)
      streamlining of neuronal communication which improves performance on a single
      task; and (ii) functional trimming of neuronal ensembles which enhances the
      capacity to accommodate processing of additional tasks, potentially by
      facilitating rapid switching of instruction sets or contexts. Finally, this study
      shows that fMRI can provide information that predicts behavioural output, which
      is not provided by overt behavioural measures.

PMID- 14691062
TI  - The cognitive ability of an incident cohort of Parkinson's patients in the UK.
      The CamPaIGN study.
AB  - We have used multiple sources to identify a population-representative cohort of
      newly diagnosed patients with parkinsonism and Parkinson's disease in the UK over
      a 2-year period. All patients have been invited to participate in a detailed
      clinical assessment either at home or in an outpatient clinic. These assessments
      have been used to refine clinical diagnoses of parkinsonism using established
      criteria, and describe some of the phenotypic variability of Parkinson's disease
      at the time of diagnosis. The crude incidence of Parkinson's disease was
      13.6/10(5yr-1) [confidence interval (CI) 11.8-15.6 and of parkinsonism was
      20.9/10(5yr-1) (CI 18.7-23.3). Age-standardized to the 1991 European population,
      the incidence figures become 10.8/10(5yr-1) (CI 9.4-12.4) for Parkinson's disease
      and 16.6/10(5yr-1) (CI 14.8-18.6) for parkinsonism. Thirty-six per cent of the
      Parkinson's disease patients had evidence of cognitive impairment based on their
      performance in the Mini-Mental State Examination, a pattern recognition task, and
      the Tower of London task. The pattern of cognitive deficits seen among these
      patients using these and further cognitive tasks suggests that sub-groups of
      patients based on cognitive ability might be identifiable even in the early
      stages of disease, which may reflect regional differences in the underlying
      neuropathological processes.

PMID- 14691063
TI  - Blood-brain barrier permeability and monocyte infiltration in experimental
      allergic encephalomyelitis: a quantitative MRI study.
AB  - Enhanced cerebrovascular permeability and cellular infiltration mark the onset of
      early multiple sclerosis lesions. So far, the precise sequence of these events
      and their role in lesion formation and disease progression remain unknown. Here
      we provide quantitative evidence that blood-brain barrier leakage is an early
      event and precedes massive cellular infiltration in the development of acute
      experimental allergic encephalomyelitis (EAE), the animal correlate of multiple
      sclerosis. Cerebrovascular leakage and monocytes infiltrates were separately
      monitored by quantitative in vivo MRI during the course of the disease. Magnetic
      resonance enhancement of the contrast agent gadolinium
      diethylenetriaminepentaacetate (Gd-DTPA), reflecting vascular leakage, occurred
      concomitantly with the onset of neurological signs and was already at a maximal
      level at this stage of the disease. Immunohistochemical analysis also confirmed
      the presence of the serum-derived proteins such as fibrinogen around the brain
      vessels early in the disease, whereas no cellular infiltrates could be detected.
      MRI further demonstrated that Gd-DTPA leakage clearly preceded monocyte
      infiltration as imaged by the contrast agent based on ultra small particles of
      iron oxide (USPIO), which was maximal only during full-blown EAE. Ultrastructural
      and immunohistochemical investigation revealed that USPIOs were present in newly
      infiltrated macrophages within the inflammatory lesions. To validate the use of
      USPIOs as a non-invasive tool to evaluate therapeutic strategies, EAE animals
      were treated with the immunomodulator 3-hydroxy-3-methylglutaryl Coenzyme A
      reductase inhibitor, lovastatin, which ameliorated clinical scores. MRI showed
      that the USPIO load in the brain was significantly diminished in lovastatin
      treated animals. Data indicate that cerebrovascular leakage and monocytic
      trafficking into the brain are two distinct processes in the development of
      inflammatory lesions during multiple sclerosis, which can be monitored on-line
      with MRI using USPIOs and Gd-DTPA as contrast agents. These studies also
      implicate that USPIOs are a valuable tool to visualize monocyte infiltration in
      vivo and quantitatively assess the efficacy of new therapeutics like lovastatin.

PMID- 14691064
TI  - Olfactory ensheathing cells genetically modified to secrete GDNF to promote
      spinal cord repair.
AB  - Olfactory ensheathing cell (OEC) transplantation has emerged as a very promising
      therapy for spinal cord repair. In this study, we tested the ability of
      genetically modified OECs to secrete high levels of glial cell line-derived
      neurotrophic factor (GDNF) to promote spinal cord repair. The GDNF gene was
      transduced into OECs using a retroviral-based system. The engineered OECs were
      first characterized by their ability to express and secrete biologically active
      GDNF in vitro. After implantation into the spinal cord of adult rats with
      complete spinal cord transection, OEC survival and GDNF production were examined.
      The locomotor functions of animals were assessed and axon regeneration was
      evaluated at the morphological level. To our knowledge, we report for the first
      time that the genetically modified OECs are capable of producing GDNF in vivo to
      significantly improve recovery after spinal cord injury (SCI). This work combined
      the outgrowth-promoting property of OECs with the neuroprotective effects of the
      additionally overexpressed neurotrophic factors and opens new avenues for the
      treatment of SCI.

PMID- 14691065
TI  - Sickness certification system in the United Kingdom: qualitative study of views
      of general practitioners in Scotland.
AB  - OBJECTIVES: To explore how general practitioners operate the sickness
      certification system, their views on the system, and suggestions for change.
      DESIGN: Qualitative focus group study consisting of 11 focus groups with 67
      participants. SETTING: General practitioners in practices in Glasgow, Tayside,
      and Highland regions, Scotland. SAMPLE: Purposive sample of general
      practitioners, with further theoretical sampling of key informant general
      practitioners to examine emerging themes. RESULTS: General practitioners believed
      that the sickness certification system failed to address complex, chronic, or
      doubtful cases. They seemed to develop various operational strategies for its
      implementation. There appeared to be important deliberate misuse of the system by
      general practitioners, possibly related to conflicts about roles and
      incongruities in the system. The doctor-patient relationship was perceived to
      conflict with the current role of general practitioners in sickness
      certification. When making decisions about certification, the general
      practitioners considered a wide variety of factors. They experienced
      contradictory demands from other system stakeholders and felt blamed for failing
      to make impossible reconciliations. They clearly identified the difficulties of
      operating the system when there was no continuity of patient care. Many wished
      either to relinquish their gatekeeper role or to continue only with major
      changes. CONCLUSIONS: Policy makers need to recognise and accommodate the range
      and complexity of factors that influence the behaviour of general practitioners
      operating as gatekeepers to the sickness certification system, before making
      changes. Such changes are otherwise unlikely to result in improvement. Models
      other than the primary care gatekeeper model should be considered.

PMID- 14691066
TI  - Alcohol licensing laws: proposals for changes in Scottish law.
AB  - Scotland, England and Wales, and Ireland have each recently reviewed how
      licensing laws might influence the increasing levels of alcohol-related problems
      in each of these countries. Each legislature has arrived at somewhat different
      recommendations. Scotland may move towards liberalization, albeit within firm
      guidelines. It is unknown whether emphasis on local review, server training and
      some restrictions on bar venues offering discount pricing, will be sufficient to
      alter current trends in alcohol-related problems.

PMID- 14691067
TI  - Phosphatidylethanol formation and degradation in human and rat blood.
AB  - AIMS: To investigate the rate of formation and degradation of phosphatidylethanol
      (PEth) in rat blood as compared to human blood, as a model for a biological
      marker for ethanol exposure. METHODS: Rats were given 9% ethanol in liquid diet
      for 30 days. Control rats were pair fed with a control liquid diet. Blood and
      organs were analysed considering PEth formed in vivo. Blood from man, rat, pig
      and ferret as well as human HepG2 cells and rat C6 glioma cells were studied with
      respect to formation and degradation of PEth in vitro. PEth was analysed by high
      performance liquid chromatography (HPLC). RESULTS: Most rat organs accumulated
      considerable amounts of PEth whereas no PEth was found in the blood. After in
      vitro incubations of blood with ethanol, PEth was only formed by human blood, in
      contrast to the other species studied. HepG2 cells and C6 cells, like human
      blood, formed PEth in vitro but only the two cell lines had enzymatic degradation
      of PEth. CONCLUSIONS: The rat is not suitable as a model for assaying PEth in
      blood as a consequence of ethanol intake. Human blood seems to be particular in
      its ability to synthesize PEth and to maintain a stable level of PEth due to the
      lack of degrading activity.

PMID- 14691068
TI  - Effect of naltrexone administration on short-term memory in chronically ethanol
      treated outbred rats.
AB  - AIMS: The purpose of this study was to evaluate the effect of naltrexone
      treatment for 21 consecutive days on short-term memory in ethanol-preferring and
      non-preferring outbred rats. METHODS: Ethanol preferring, non-preferring and
      control Wistar rats were treated with naltrexone [0.1 mg/kg intraperitoneally
      (i.p.)] for 21 consecutive days. Short-term memory was assessed by using an
      olfactory social recognition test. RESULTS: A single administration of naltrexone
      (0.1 mg/kg i.p.) to non-ethanol-treated animals facilitated social memory,
      whereas the drug did not affect short-term memory in either group of chronically
      ethanol-treated rats. Multiple naltrexone treatment also lowered alcohol intake
      in ethanol-preferring rats. CONCLUSION: Naltrexone-ethanol interaction does not
      seem to produce any negative effect on the short-term memory in outbred rats.

PMID- 14691069
TI  - Genetic polymorphisms in alcohol-metabolizing enzymes and chronic pancreatitis.
AB  - AIMS: Alcohol misuse is now regarded as an important risk factor for development
      of chronic pancreatitis (CP). However, not every alcohol misuser develops CP and
      it therefore might be suggested that susceptibility could be further influenced
      by inter-individual variations in the activities of alcohol-metabolizing enzymes.
      Several genetic polymorphisms that may affect the activities of alcohol
      metabolizing enzymes have been described. Therefore we determined whether
      polymorphisms in the genes for alcohol dehydrogenase 3 (ADH3) or cytochrome p450
      2E1 (CYP2E1) predispose to the development of CP. METHODS: DNA samples were
      obtained from 142 adult CP patients with hereditary (n = 21), alcoholic (n = 82)
      or idiopathic (n = 39) CP. DNA from 128 healthy controls and from 93 alcoholic
      controls was analysed for comparison. Patients and controls were all of Caucasian
      origin. Genetic polymorphisms in ADH3 and CYP2E1 were determined by PCR, followed
      by restriction-fragment-length-polymorphism analyses in all subjects. RESULTS:
      The frequencies of ADH3 and CYP2E1 c1c2 genotypes did not differ between CP
      patients and alcoholic and healthy controls. However, a trend for a higher
      frequency of the CYP2E1 intron 6 D allele was demonstrated in patients with
      alcohol-induced CP, compared to that of healthy controls (OR = 3.03, 95%CI = 1.0
      9.1) or alcoholic controls (OR = 2.76, 95%CI = 0.9-8.7). CONCLUSIONS: These data
      suggest that the presence of the CYP2E1 intron 6 DD genotype might confer a
      higher risk of alcoholic CP.

PMID- 14691071
TI  - Down your drink: a web-based intervention for people with excessive alcohol
      consumption.
AB  - AIMS: To conduct a pilot study of the usefulness of Down Your Drink (DYD), a web
      based intervention to encourage excessive drinkers to adopt a healthy pattern of
      drinking and reduce alcohol-associated harm. The DYD website was structured as a
      6-week programme, derived from a manual which included elements of motivational
      approaches and cognitive behavioural therapy. METHODS: Visitors whose responses
      to the Fast Alcohol Screening Test were positive, and those indicating excessive
      alcohol consumption, were encouraged to register. Users completed alcohol
      dependence and mental health questionnaires before the programme, and a drinking
      diary at each of the weekly sessions. Follow-up questionnaires were sent
      electronically to those who completed the programme, or who missed three or more
      sessions. RESULTS: During the 6-month study there were 7581 visits to the site
      and 1319 registrations. Of the registrants, 61.8% completed week 1, and 6.0%
      stayed with the programme until the end. The 6% who stayed for 6 weeks provided
      encouraging feedback about the value of the site. Little information was obtained
      from those who dropped out, but some reported that the programme was too time
      consuming. CONCLUSIONS: Web site interventions for excessive drinkers are
      feasible and merit evaluation of their effectiveness.

PMID- 14691070
TI  - Association of cholecystokinin-A receptor gene polymorphism with alcohol
      dependence in a Japanese population.
AB  - AIMS: Cholecystokinin (CCK), one of the most abundant neurotransmitter peptides,
      interacts with dopamine. Dopaminergic neurotransmission between the ventral
      tegmental area and the limbic forebrain is a critical neurobiological component
      of alcohol and drug self-administration. CCK modulates dopamine release in the
      nucleus accumbens via the CCK-A receptor (R). We recently determined the
      transcriptional start site of the human CCK-AR gene, and detected two sequence
      changes (-81A/G and -128G/T) in the promoter region. The aims of the present
      study were to determine the prevalence of the -81A/G and -128G/T polymorphism of
      the CCK-AR gene between alcoholics and normal control subjects and the
      occurrences of the polymorphisms in subtypes of alcoholics. METHODS: The above
      polymorphisms were examined in 435 alcoholics and 1490 control subjects. We
      excluded subjects with inactive ALDH2 and employed the subjects with ALDH2*1/2*1
      (384 alcoholics and 792 controls). RESULTS: The allelic frequency of -81G in the
      CCK-AR gene polymorphism (-81A/G) was significantly higher in alcoholics than in
      control subjects. However, there were no differences between the two groups with
      respect to the frequency of -128G/T. Alcoholic patients with antisocial
      personality disorder and with first-degree alcoholic relatives were significantly
      associated with a higher frequency of the -81G allele. In addition, the age of
      onset of alcohol dependence was significantly earlier in patients with this
      allele. CONCLUSIONS: The CCK-AR gene -81A/G polymorphism, especially in the -81G
      allele, may be associated with intractable alcoholism.

PMID- 14691072
TI  - Concentration of fatty acid ethyl esters in hair of alcoholics: comparison to
      other biological state markers and self reported-ethanol intake.
AB  - AIMS: In a variety of clinical and forensic situations long term use of alcohol
      must be monitored. In this project we explore the utility of fatty acid ethyl
      esters (FAEE) in this regard. Additionally, we propose a cut-off value of FAEE to
      distinguish teetotallers/moderate/social drinkers from alcoholics or individuals
      drinking at harmful levels. PATIENTS AND METHODS: FAEE levels from 18 alcohol
      dependent patients in detoxification were contrasted with those of 10 social
      drinkers and 10 teetotallers. FAEE in hair were determined, using headspace solid
      phase microextraction and gas chromatography mass spectrometry. C(FAEE), as sum
      of the concentrations of four esters, was compared to a major FAEE, ethyl
      palmitate. PEth was measured in heparinized whole blood with a high pressure
      liquid chromatography (HPLC) method. Drinking validation criteria include self
      reports, phosphatidyl ethanol (PEth) in whole blood as well as the traditional
      markers of heavy drinking, gamma glutamyl transpeptidase (GGT), mean corpuscular
      volume (MCV) and carbohydrate deficient transferrin (CDT). RESULTS: Receiver
      operating characteristic (ROC) curve analysis for C(FAEE), indicated a
      sensitivity of 100% and a specificity of 90% for a cut-off of 0.29 ng/mg. By
      using a cut-off of 0.4 ng/mg, C(FAEE) identified 94.4% correctly. C(FAEE) and
      ethyl palmitate were significantly associated (r = 0.945; P < 0.001) as were
      C(FAEE) and PEth (r = 0.527; P = 0.025). No significant correlation was found
      between C(FAEE) and total grams of ethanol consumed last month, blood-alcohol
      concentration at admission to the hospital, CDT, MCV, or GGT. Among the serum and
      blood markers, %CDT identified 47.1%, MCV 38.8% and GGT 72.2% of patients with
      chronic intake of higher amounts of ethanol correctly, whereas PEth achieved 100%
      accuracy. CONCLUSIONS: The data suggest that C(FAEE) is a potentially valuable
      marker of chronic intake of high quantities of ethanol. Furthermore, the results
      indicate that a reasonable and provisional FAEE cut-off to distinguish between
      social/moderate and heavy drinking/alcoholism in hair is 0.4 ng/mg.

PMID- 14691073
TI  - Type of alcoholic beverage and high-risk drinking: how risky is beer drinking in
      Korea?
AB  - AIMS: To examine the association of beverage type with high-risk drinking in
      Korea. METHODS: Data were analysed from the Korea's 1997 behavioural risk factor
      surveillance system survey collected by a stratified random sampling method (n =
      1045). After alcohol consumption per drinking day was categorized into three risk
      levels for short-term or 'acute' harm on the basis of the World Health
      Organization's guidelines, logistic regression analysis adjusting for socio
      demographic factors was performed for each beverage type. RESULTS: Using beer
      drinkers as the reference, those who drank soju (the most widely consumed
      traditional beverage in Korea) showed an adjusted odds ratio (OR) of 3.62 [95%
      confidence interval (CI) = 2.28-5.76] for high and very high risk from drinking
      and those who drank spirits had adjusted OR of 10.65 (95%CI = 4.32-26.27).
      CONCLUSIONS: In Korea, unlike in many western countries, beer is not the highest
      risk beverage. The relatively high price of beer in Korea is likely to be one
      influence. It is concluded that country-specific differences are important in
      studies on associations between alcoholic beverage types and high risk drinking.

PMID- 14691074
TI  - Drinking and drinking patterns and health status in the general population of
      five areas of China.
AB  - AIMS: To understand drinking patterns, health status related to drinking and the
      level of unrecorded alcoholic beverage consumption for the general population
      living in five areas of China in 2001. METHODS: By cluster sampling, 24992
      community residents aged 15 years or older were interviewed by trained
      psychiatrists using structured questionnaires provided by WHO. RESULTS: The 1
      year drinking rate was 59.0%, and the point prevalence rate of dependence was
      3.8%. The average annual consumption of pure alcohol was 4.47 l. The 1-year
      morbidity from gastritis/ulcer in the whole sample was 7.9%, which associated
      nonlinearly to alcohol intake, and heart disease and cerebral infarction/cerebral
      haemorrhage showed V-shaped curve relationships. CONCLUSIONS: The rate of alcohol
      use was higher in men than in women, and the annual alcohol consumption per
      capita was higher than that in the 1990s in the selected areas. Alcohol
      consumption plays a role in the development of alcohol-related physical diseases.

PMID- 14691075
TI  - Relationship between ethanol-induced changes in brain regional metabolism and its
      motor, behavioural and cognitive effects.
AB  - AIMS AND METHODS: Acute alcohol administration induces marked decreases in
      glucose metabolism throughout the human brain. However, the relationship between
      alcohol's effects on brain metabolism and the behavioural changes that occur with
      intoxication are still unclear. Here we assessed this association using principal
      component analysis for dimension reduction and canonical correlations to gauge
      inter-class relationships. We also used canonical correlations in the polynomial
      space to assess for possible nonlinear relationships. RESULTS: After normalizing
      the regional measures to account for the large whole brain decreases observed
      with intoxication we show that the largest decreases occurred in occipital cortex
      and that there were relative increases in basal ganglia. Principal component
      analysis of the changes in the normalized measures revealed that 60% of the
      variance was accounted for by two factors; one that contrasted cerebellum versus
      frontal and anterior cingulate metabolism, and another that contrasted basal
      ganglia and insula. The square of the first factor was significantly correlated
      with the deterioration in cognitive performance. The second factor showed a
      significant linear correlation with self-reports of intoxication and with
      deterioration in cognitive and motor performance. CONCLUSIONS: These findings
      suggest that the contrasting effects of alcohol in basal ganglia versus the
      insula are involved in the perception of 'feeling drunk' and that its contrasting
      effects in cerebellum versus those in frontal and parietal cortices are involved
      in its motor incoordinating effects. On the other hand alcohol's impact on
      cognitive performance implicates a more complex pattern of brain effects that
      includes linear as well as non-linear associations.

PMID- 14691076
TI  - Method-dependent characteristics of carbohydrate-deficient transferrin
      measurements in the follow-up of alcoholics.
AB  - AIMS: There are only limited data comparing the diagnostic characteristics of
      carbohydrate-deficient transferrin (CDT) measurements in assays for excessive
      alcohol consumption under controlled conditions. METHODS: We compared different
      CDT assays and the conventional laboratory markers of ethanol consumption, gamma
      glutamyl transferase (gamma-GT) aspartate aminotransferase (AST) and mean
      corpuscular volume (MCV) in the assessment and follow-up of 36 alcoholics (31
      men, five women, mean age 44 years), who were admitted for detoxification.
      Detailed interviews to assess the amount of alcohol consumption were carried out
      for each patient. A hospital follow-up with supervised abstinence for 8 +/- 4
      days (range 5-19 days) was carried out for 17 patients. Controls were 30
      apparently healthy individuals (22 men, eight women, mean age 49 years), who had
      no history of hazardous drinking. RESULTS: At the time of admission, the %CDT
      method, which excludes the trisialotransferrin isoform from the measurement,
      yielded elevated values in 69% of the patients, compared to 61% for CDTect. The
      corresponding sensitivities for gamma-GT, AST and MCV were 61, 56 and 47%,
      respectively. The self-reported alcohol consumption for a period of 1 month prior
      to admission showed a stronger correlation with the %CDT results (r = 0.59, P =
      0.0003) than with the CDTect results (r = 0.36, P = 0.04), GT (r = 0.40, P =
      0.02) or AST (r = 0.35, P = 0.05). During follow-up with supervised abstinence
      the mean %CDT values were found to show a slower rate to normalization (mean 14
      +/- 4 days) than the CDT values measured with the CDTect method (mean 10 +/- 5
      days) (P < 0.05). CONCLUSIONS: The data indicate distinct differences and method
      dependent rates of normalization in CDT assays, possibly reflecting different
      degrees of transferrin desialylation in the alcoholics. The present findings
      should be considered in studies on alcohol markers for monitoring abstinence.

PMID- 14691077
TI  - Trends in alcohol intake by education and marital status in urban population in
      Russia between the mid 1980s and the mid 1990s.
AB  - AIMS: We investigated changes in the distribution of alcohol consumption by
      education and marital status in Russia during the period of societal
      transformation after 1990. Such changes would indicate the potential role of
      alcohol in the rising social inequalities in mortality. METHODS: We analysed data
      from three surveys in random population samples conducted in Novosibirsk as part
      of the WHO MONICA project in 1985/86 (1533 men, 1292 women), 1988/89 (1700 men,
      no women) and 1994/95 (1526 men, 1510 women), coinciding with the period of
      societal transformation. Four measures of drinking were examined in relation to
      education and marital status: prevalence of drinking at least twice a week; the
      mean intake in the last week; the mean intake per drinking occasion; and the
      prevalence of binge drinking (>80 g ethanol for men and >60 g for women) at least
      once a month. RESULTS: Among men, those with university education had the lowest
      levels of all measures of drinking. Drinking indices increased over time in all
      educational groups but most sharply in men with high education, thus leading to a
      smaller education-related difference in the last survey. With respect to marital
      status, divorced and widowed men tended to drink most, but the pattern was
      inconsistent, and the difference between divorced and married men also narrowed
      over time. Among women, alcohol intake increased between the first and last
      survey. Differences by education and marital status in women were smaller than in
      men, and binge drinking was inversely related to education. CONCLUSIONS: All
      indices of alcohol consumption in men increased between the mid 1980s and the mid
      1990s. The increase in alcohol intake among men was proportionally similar across
      categories of education and marital status but the absolute differences
      increased. The contribution of alcohol to the increase in social differentials in
      mortality in the 1990s was probably modest.

PMID- 14691086
TI  - The binding and recall of snapshot memories in wood ants (Formica rufa L.).
AB  - Insects can locate spatial goals by means of 2-D retinotopic views of the
      surrounding landmarks, which they memorise from the vantage point of the goal.
      Wood ants acquire such snapshot memories while fixating conspicuous landmarks
      with frontal retina, and their snapshots extend horizontally at least 120 degrees
      into the periphery. Are spatially separate items within such an extended snapshot
      bound together so that a snapshot is recalled as a whole, or are its components
      recognised individually? We approached this question by training ants to find
      food midway between two upright black cylinders of different sizes and then
      examined where they searched when they were given two cylinders of the same size.
      If the ants know which cylinder replaces the small cylinder and which the large,
      they should search at a position where the two equal-sized cylinders subtend the
      same angles as do the training cylinders when viewed from the feeder. Ants
      conformed to this prediction under one condition, searching at a shorter distance
      from the substitute for the large cylinder than from the substitute for the small
      cylinder. But, under another condition, ants were unable to distinguish between
      the two equal-sized cylinders. Ants failed when white curtains completely
      surrounded the platform on which the cylinders were placed. They succeeded when
      one side of the platform had a patterned curtain. We suggest that ants take two
      snapshots at the feeding site, one when facing the small cylinder and one when
      facing the large cylinder, and that each snapshot includes the patterned curtain,
      if it is there. Ants will view the patterned curtain with the lateral retina of
      one eye when facing the small cylinder and with the lateral retina of the other
      eye when facing the large cylinder. Our data suggest that there may be
      associative links between these spatially separate components of the snapshot,
      which cause the memory of the small cylinder or the large cylinder to be recalled
      according to which eye sees the curtain. It seems that an extended snapshot not
      only enhances the accuracy of localisation but can also increase the reliability
      of snapshot recall, provided that the components of a snapshot are bound
      together.

PMID- 14691087
TI  - Walking and running in the red-legged running frog, Kassina maculata.
AB  - Although most frog species are specialized for jumping or swimming, Kassina
      maculata (red-legged running frog) primarily uses a third type of locomotion
      during which the hindlimbs alternate. In the present study, we examined Kassina's
      distinct locomotory mode to determine whether these frogs walk or run and how
      their gait may change with speed. We used multiple methods to distinguish between
      terrestrial gaits: the existence or absence of an aerial phase, duty factor,
      relative footfall patterns and the mechanics of the animal's center of mass
      (COM). To measure kinematic and kinetic variables, we recorded digital video as
      the animals moved over a miniature force platform (N=12 individuals). With
      respect to footfall patterns, the frogs used a single gait and walked at all
      speeds examined. Duty factor always exceeded 0.59. Based on COM mechanics,
      however, the frogs used both walking and running gaits. At slower speeds, the
      fluctuations in the horizontal kinetic energy (E(k)) and gravitational potential
      energy (E(p)) of the COM were largely out of phase, indicating a vaulting or
      walking gait. In most of the trials, Kassina used a combined gait at intermediate
      speeds, unlike cursorial animals with distinct gait transitions. This combined
      gait, much like a mammalian gallop, exhibited the mechanics of both vaulting and
      bouncing gaits. At faster speeds, the E(k) and E(p) of Kassina's COM were more in
      phase, indicating the use of a bouncing or running gait. Depending on the
      definition used to distinguish between walking and running, Kassina either only
      used a walking gait at all speeds or used a walking gait at slower speeds but
      then switched to a running gait as speed increased.

PMID- 14691088
TI  - Stimulation of the alpha-adrenoceptor triggers the venom production cycle in the
      venom gland of Bothrops jararaca.
AB  - The noradrenergic innervation of Bothrops jararaca venom gland is thought to be
      important in the production and secretion of venom. We investigated the
      characteristics of the alpha-adrenoceptor in the venom gland and its role in
      venom production. This receptor had relatively low sensitivity to noradrenaline
      (pD(2)=4.77+/-0.09, N=7) and to phenylephrine (pD(2)=3.77+/-0.06, N=11). The
      receptor became desensitized just after venom extraction (pD(2) to phenylephrine
      fell to 3.27+/-0.02, N=6) and the sensitivity remained low for at least 15 days,
      returning to normal 30 days after venom extraction, by which time the snake was
      ready for a new cycle of venom production. Incubation of secretory cells with
      noradrenaline (10(-4) mol l(-1) for 5 min) reduced alpha-adrenoceptor sensitivity
      to the level seen after venom extraction. Blockade of catecholamine production
      with reserpine abolished the enlargement of the rough endoplasmic reticulum and
      the activation of the Golgi apparatus that are normally seen after venom
      extraction, and the venom production was restored by a single subcutaneous (s.c.)
      injection of phenylephrine (100 mg kg(-1)) immediately after venom extraction.
      Our data suggest that stimulation of the alpha-adrenoceptor during or shortly
      after biting is essential for the onset of the venom production cycle.

PMID- 14691089
TI  - Allometry of maximum vertical force production during hovering flight of
      neotropical orchid bees (Apidae: Euglossini).
AB  - The ability of orchid bees to generate vertical forces was evaluated using a load
      lifting method that imposed asymptotically increasing loads during ascending
      flight, ultimately eliciting maximum forces while hovering. Among 11 orchid bee
      species varying by approximately an order of magnitude in body mass, the capacity
      to produce vertical forces expressed relative either to body weight or to flight
      muscle weight declined linearly with increased body mass. Allometric analysis of
      log-transformed data, by contrast, found maximum vertical force to scale
      isometrically with body mass, but also to exhibit a slightly negative allometry
      with respect to flight muscle mass. Maximum stroke amplitude at limiting loads
      averaged 140 degrees and was remarkably constant among species, a result
      consistent with anatomical constraints of the hymenopteran thorax on wing
      motions. By contrast, wing-beat frequencies during maximum performance declined
      with increasing body mass. Repeated lifting by individual bees reduced
      performance only when the number of consecutive lifts exceeded 15. Variation in
      linear mass density of the lifted load did not systematically alter performance
      estimates, although measurements on one species in two consecutive years at
      different thermal environments yielded significant differences in estimates of
      maximum force production. These findings suggest an adverse scaling of vertical
      force production at greater body mass even if flight muscle mass scales
      isometrically.

PMID- 14691090
TI  - Noise-induced stress response and hearing loss in goldfish (Carassius auratus).
AB  - Fishes are often exposed to environmental sounds such as those associated with
      shipping, seismic experiments, sonar and/or aquaculture pump systems. While
      efforts have been made to document the effects of such anthropogenic (human
      generated) sounds on marine mammals, the effects of excess noise on fishes are
      poorly understood. We examined the short- and long-term effects of increased
      ambient sound on the stress and hearing of goldfish (Carassius auratus; a hearing
      specialist). We reared fish under either quiet (110-125 dB re 1 microPa) or noisy
      (white noise, 160-170 dB re 1 microPa) conditions and examined animals after
      specific durations of noise exposure. We assessed noise-induced alterations in
      physiological stress by measuring plasma cortisol and glucose levels and in
      hearing capabilities by using auditory brainstem responses. Noise exposure did
      not produce long-term physiological stress responses in goldfish, but a transient
      spike in plasma cortisol did occur within 10 min of the noise onset. Goldfish had
      significant threshold shifts in hearing after only 10 min of noise exposure, and
      these shifts increased linearly up to approximately 28 dB after 24 h of noise
      exposure. Further noise exposure did not increase threshold shifts, suggesting an
      asymptote of maximal hearing loss within 24 h. After 21 days of noise exposure,
      it took goldfish 14 days to fully recover to control hearing levels. This study
      shows that hearing-specialist fishes may be susceptible to noise-induced stress
      and hearing loss.

PMID- 14691091
TI  - Inhibition of the increased 17beta-estradiol-induced mast cell number by
      melatonin in the testis of the frog Rana esculenta, in vivo and in vitro.
AB  - In the present study, we have utilized 17beta-estradiol to induce the increase of
      mast cell number in order to verify the melatonin effect on mast cell
      accumulation in the frog testicular interstitium. Data obtained from in vivo
      experiments confirm that 17beta-estradiol increases the mast cell number and
      indicate a melatonin-inhibitory role in their accumulation in the frog testis. In
      addition, melatonin interferes with the effects of estradiol on the increase of
      mast cell number in short-term cultured testes, and this result has also been
      obtained in a dose-response experiment at physiological concentration. The data
      suggest that melatonin acts on mast cell number directly via its local action in
      the frog gonads. In conclusion, our study shows, for the first time, that
      melatonin may interfere, probably via estrogen receptors, with the
      differentiation and/or proliferation of mast cells induced by estradiol treatment
      either in vivo or in vitro in the testis of the frog Rana esculenta.

PMID- 14691092
TI  - Acoustic communication in noise: regulation of call characteristics in a New
      World monkey.
AB  - This study on common marmosets Callithrix jacchus is the first to examine noise
      dependent mechanisms of vocal plasticity in a New World monkey. Since acoustic
      communication can be considerably impaired by environmental noise, some animals
      have evolved adaptations to counteract its masking effects. The studied marmosets
      increased the sound level of their spontaneous calls in response to increased
      levels of white noise broadcast to them. Possibly, such noise-dependent
      adjustment of vocal amplitude serves to maintain a specific signal-to-noise ratio
      that is favourable for signal production. Concurrently, the adjustment of vocal
      amplitude can maintain a given active space for communication. In contrast to
      some bird species, no noise-induced increase in the number of syllables per call
      series could be found, showing that an increased serial redundancy of vocal
      signals was not used to communicate under noisy conditions. Finally, we examined
      a possible noise-dependent prolongation of vocal signals. This approach was
      guided by the findings of perceptional studies, which suggest an increased
      detection probability of prolonged signals in noise by temporal summation.
      Marmosets indeed increased the duration of their call syllables along with
      increasing background noise levels. This is the first evidence of such mechanism
      of vocal plasticity in an animal communication system.

PMID- 14691093
TI  - Unsteady forces and flows in low Reynolds number hovering flight: two-dimensional
      computations vs robotic wing experiments.
AB  - We compare computational, experimental and quasi-steady forces in a generic
      hovering wing undergoing sinusoidal motion along a horizontal stroke plane. In
      particular, we investigate unsteady effects and compare two-dimensional (2D)
      computations and three-dimensional (3D) experiments in several qualitatively
      different kinematic patterns. In all cases, the computed drag compares well with
      the experiments. The computed lift agrees in the cases in which the sinusoidal
      changes in angle of attack are symmetrical or advanced with respect to stroke
      positions, but lags behind the measured 3D lift in the delayed case. In the range
      of amplitudes studied here, 3-5 chords, the force coefficients have a weak
      dependence on stroke amplitude. As expected, the forces are sensitive to the
      phase between stroke angle and angle of attack, a result that can be explained by
      the orientation of the wing at reversal. This dependence on amplitude and phase
      suggests a simple maneuver strategy that could be used by a flapping wing device.
      In all cases the unsteady forces quickly reach an almost periodic state with
      continuous flapping. The fluid forces are dominated by the pressure contribution.
      The force component directly proportional to the linear acceleration is smaller
      by a factor proportional to the ratio of wing thickness and stroke amplitude; its
      net contribution is zero in hovering. The ratio of wing inertia and fluid force
      is proportional to the product of the ratio of wing and fluid density and the
      ratio of wing thickness and stroke amplitude; it is negligible in the robotic
      wing experiment, but need not be in insect flight. To identify unsteady effects
      associated with wing acceleration, and coupling between rotation and translation,
      as well as wake capture, we examine the difference between the unsteady forces
      and the estimates based on translational velocities, and compare them against the
      estimate of the coupling between rotation and translation, which have simple
      analytic forms for sinusoidal motions. The agreement and disagreement between the
      computed forces and experiments offer further insight into when the 3D effects
      are important. A main difference between a 3D revolving wing and a 2D translating
      wing is the absence of vortex shedding by a revolving wing over a distance much
      longer than the typical stroke length of insects. No doubt such a difference in
      shedding dynamics is responsible in part for the differences in steady state
      force coefficients measured in 2D and 3D. On the other hand, it is unclear
      whether such differences would have a significant effect on transient force
      coefficients before the onset of shedding. While the 2D steady state force
      coefficients underpredict 3D forces, the transient 2D forces measured prior to
      shedding are much closer to the 3D forces. In the cases studied here, the chord
      is moving between 3 to 5 chords, typical of hovering insect stroke length, and
      the flow does not appear to separate during each stroke in the cases of advanced
      and symmetrical rotation. In these cases, the wing reverses before the leading
      edge vortex would have time to separate even in 2D. This suggests that the time
      scale for flow separation in these strokes is dictated by the flapping frequency,
      which is dimensionally independent. In such cases, the 2D unsteady forces turn
      out to be good approximations of 3D experiments.

PMID- 14691094
TI  - Kinematics of the transition between aquatic and terrestrial locomotion in the
      newt Taricha torosa.
AB  - California newts (Taricha torosa) are capable of locomotion in both aquatic and
      terrestrial environments. The transition between swimming and terrestrial walking
      was examined by videotaping individual Taricha walking both up and down a ramp,
      inclined at 15 degrees to the horizontal, that had its lower end immersed in
      water and its upper end out of the water. When ascending the ramp, California
      newts first approached it by swimming, then used their limbs to walk while still
      in water, and finally left the water using a normal terrestrial walking gait. The
      reverse of this sequence was observed when individuals descended the ramp. In
      both directions, Taricha used a lateral sequence walk with a duty factor of
      approximately 76% when out of the water. Timing of footfalls was more variable in
      water and featured shorter duty factors, leading to periods of suspension.
      Comparison of angular and timing variables revealed effects due to direction and
      degree of immersion. Few timing variables showed differences according to stride
      within sequence (indicating whether the animal was in or out of the water),
      suggesting that the basic walking pattern is equally good in both environments.

PMID- 14691095
TI  - Effect of aestivation on long bone mechanical properties in the green-striped
      burrowing frog, Cyclorana alboguttata.
AB  - The green-striped burrowing frog, Cyclorana alboguttata, survives extended
      drought periods by burrowing underground and aestivating. These frogs remain
      immobile within cocoons of shed skin and mucus during aestivation and emerge from
      their burrows upon heavy rains to feed and reproduce. Extended periods of
      immobilisation in mammals typically result in bone remodelling and a decrease in
      bone strength. We examined the effect of aestivation and, hence, prolonged
      immobilisation on cross-sectional area, histology and bending strength in the
      femur and tibiofibula of C. alboguttata. Frogs were aestivated in soil for three
      and nine months and were compared with control animals that remained active, were
      fed and had a continual supply of water. Compared with the controls, long bone
      size, anatomy and bending strength remained unchanged, indicating an absence of
      disuse osteoporosis. This preservation of bone tissue properties enables C.
      alboguttata to compress the active portions of their life history into
      unpredictable windows of opportunity, whenever heavy rains occur.

PMID- 14691097
TI  - Development of respiratory function in the American locust Schistocerca
      americana. I. Across-instar effects.
AB  - We tested the hypothesis that oxygen delivery from the atmosphere to the tissues
      becomes more difficult as grasshoppers increase in body size throughout
      development due to increases in tracheal length. If this is true, then older,
      larger grasshoppers should have smaller safety margins [higher critical oxygen
      partial pressures (P(O2)s)] for oxygen delivery than younger, smaller
      grasshoppers. We exposed grasshoppers of first, third and fifth instars and
      adults to decreasing levels of atmospheric O2 and measured their ventilatory
      responses. Contrary to our prediction, we found that larger grasshoppers had
      critical P(O2)s eight times lower than juveniles due in part to their threefold
      lower mass-specific metabolic rates and their ability to quadruple convective gas
      exchange. Adults more than doubled abdominal pumping frequency and increased
      tidal volume by 25% as P(O2) decreased fourfold, whereas the youngest juveniles
      showed no such responses. This study indicates that juveniles may be more
      susceptible to hypoxia in natural situations, such as exposure to high altitude
      or restricted burrows. Also, larger size is not necessarily correlated with a
      smaller safety margin for oxygen delivery in insects.

PMID- 14691096
TI  - Morphological and functional maturation of a skeletal muscle regulated by
      juvenile hormone.
AB  - Reproductive behaviour of animals requires a well-adapted muscular system. This
      study examines the structural and functional development of ovipositor muscle
      properties in female locusts during reproductive development. A possible
      regulation by juvenile hormone (JH) was assessed by comparing muscle properties
      in immature and mature females and with those whose JH production was inhibited
      by allatectomy early in adult life. The results are related to the reproductive
      behaviour of locusts. Histological and ultrastructural comparison of muscle
      fibres and their associated cuticular structures (apodemes) revealed dramatic
      growth during the first 2 weeks of reproductive development. The cross-sectional
      area of muscle fibres increased sevenfold, and their mass-per-length 5.3-fold.
      Ultrastructural examination showed growth of mitochondria, development of
      sarcoplasmic reticulum and increasing levels of structural organisation of
      myofibrils. Muscles of mature females displayed pronounced fatigue resistance,
      contracted more powerfully (twitch, 33.22+/-10.8 mN; 50 Hz, 623.66+/-115.77 mN)
      and had almost two times faster kinetics than those of immature females (twitch,
      6.5+/-2.6 mN; 50 Hz, 14.19+/-2.58 mN). Together with muscular maturation,
      cuticular apodemes, which serve as attachment sides for ovipositor muscles, grow
      considerably in length and width and assume a complex surface structure. Most of
      the described changes were suppressed in females deprived of JH (allatectomised).
      The results demonstrate an adaptation of muscle properties to the requirements of
      reproductive behaviour that is largely regulated by juvenile hormone.

PMID- 14691098
TI  - Development of respiratory function in the American locust Schistocerca
      americana. II. Within-instar effects.
AB  - We hypothesized that oxygen delivery becomes more difficult for insects and
      tracheate arthropods as they progress throughout an intermolt period. During this
      time, body mass can more than double, yet the major tracheae and spiracles cannot
      be increased in size until molting. Also, tissue growth could compress air sacs
      used for convective gas exchange. To test these possibilities, we investigated
      the effect of within-instar growth on respiratory parameters, including CO(2)
      emission rate, ventilation frequency, tidal volume and critical oxygen partial
      pressure (P(O2)) for first-, third- and fifth-instar juveniles and adults of the
      American locust Schistocerca americana. We found that late-stage grasshoppers
      tended to have 40% higher total CO(2) emission rates but 15% lower mass-specific
      CO(2) emission rates and 35% higher ventilation frequencies than early-stage
      animals. Maximal tracheal system conductance decreased by 20-33% at the end of an
      instar, possibly due to compression of air sacs. In addition, animals nearing the
      end of an instar had higher critical P(O2) values for abdominal pumping, and late
      stage adults had 50% lower tidal volumes, suggesting that increases in tissue
      mass throughout an instar may hinder the ability of animals to breathe deeply.
      Late-stage adults had lower critical P(O2) values for CO(2) emission, although
      this pattern was not found in any juvenile instars, indicating that late-stage
      juveniles compensate for decreased conductance by increasing ventilation
      frequency or the use of diffusive gas exchange. Our data suggest that late-stage
      arthropods are more vulnerable to hypoxia and may have reduced aerobic capacities
      and lower tissue P(O2)s than early-stage arthropods.

PMID- 14691099
TI  - Effects of leucokinin-VIII on Aedes Malpighian tubule segments lacking stellate
      cells.
AB  - The diuretic peptide leucokinin is known to increase fluid secretion in
      Malpighian tubules of the yellow fever mosquito Aedes aegypti by increasing a
      transepithelial Cl(-) conductance. The present study sought to examine whether
      stellate cells provided this transepithelial conductance in Aedes Malpighian
      tubules as they do in Drosophila Malpighian tubules. Aedes Malpighian tubule
      segments with and without stellate cells were perfused in vitro for measurements
      of the transepithelial voltage (V(t)), resistance (R(t)) and Cl(-) diffusion
      potentials (DP(Cl)). In 11 tubule segments containing both principal cells and
      stellate cells, 1 micro mol l(-1) leucokinin-VIII added to the peritubular bath
      immediately and significantly decreased V(t) from 39.3+/-14.3 mV to 2.3+/-0.7 mV,
      decreased R(t) from 12.4+/-2.6 kOmegacm to 2.4+/-0.3 kOmegacm, and increased
      DP(Cl) from 8.2+/-1.2 mV to 42.1+/-5.4 mV. These effects of leucokinin-VIII were
      qualitatively and quantitatively similar in six tubule segments containing no
      stellate cells; V(t) decreased from 37.8+/-7.0 mV to 3.4+/-0.6 mV, R(t) decreased
      from 8.8+/-2.1 kOmegacm to 1.7+/-0.2 kOmegacm, and DP(Cl) increased from 5.8+/
      2.6 mV to 50.0+/-2.1 mV. Thus, stellate cells are not required for signaling or
      mediating the effects of leucokinin in Malpighian tubules of Aedes aegypti. The
      results further support previous observations that principal cells signal the
      effects of leucokinin to increase the Cl(-) conductance of the paracellular
      pathway through septate (or tight) junctions.

PMID- 14691100
TI  - Future migratory behaviour predicted from premigratory levels of gill Na+/K+
      ATPase activity in individual wild brown trout (Salmo trutta).
AB  - The relationship between premigratory gill Na+/K+-ATPase activity, determined at
      two dates during spring, and future migratory behaviour was investigated using
      non-lethal gill biopsies and PIT-tagging in wild brown trout (Salmo trutta) from
      two tributaries. No significant relationship between future migratory strategy
      (individuals eventually becoming migrants or residents) and gill Na+/K+-ATPase
      activity was found in late February-early March. By contrast, in mid-April, a
      highly significant logistic regression equation identifying the migratory
      strategy in 93% of the 75 individuals was obtained. The ability of this
      regression model from the tributaries to predict future migratory behaviour in an
      independent group of trout caught in early April in the mainstream was evaluated.
      A threshold probability of migration was used to predict the behaviour of the
      mainstream individuals as either future migrants or residents. The maximum
      percentage of correct predictions of future migratory behaviour in mainstream
      fish was observed at threshold probabilities between approximately 0.15 and 0.45
      (corresponding to threshold gill Na+/K+-ATPase activities between 2.7 and 3.7
      micromol ADP mg(-1) protein h(-1)), with an average of 91% of the predictions
      being correct. The present study shows that a non-lethal premigratory biochemical
      measurement can successfully select individual brown trout with high probability
      of migration.

PMID- 14691101
TI  - Strikes and startles of northern pike (Esox lucius): a comparison of muscle
      activity and kinematics between S-start behaviors.
AB  - S-starts are a major class of fast-start behaviors that serve diverse locomotor
      functions in fishes, playing roles in both feeding strike and escape startle
      events. While movement patterns are similar during strike and startle, their
      motor control mechanisms have not been compared. To investigate heterogeneity in
      S-start responses and to test the hypothesis that S-starts are generated by the
      same patterns of muscle activity regardless of the behavioral context in which
      they function, we examined kinematic and muscle activity patterns of northern
      pike (Esox lucius) performing feeding and escape S-starts. Movements were
      recorded with high-speed video (250 Hz). Muscle activity was recorded from seven
      electrodes, one in the left adductor mandibulae and bilaterally in the anterior,
      midbody and posterior epaxial white muscle. Although S-shaped movements are
      produced in both feeding and escape, kinematics and electromyogram (EMG) patterns
      differ. Stage 1 (pre-propulsive movement) is significantly slower and more
      variable during feeding strikes and involves caudal bending with less rostral
      movement than recorded for startle behaviors. Correspondingly, there is strong
      caudal muscle activity prior to rostral activity during strikes, whereas in
      startles caudal muscle activity had near simultaneous onset with contralateral
      rostral activity. Onset of jaw muscle activity occurred significantly after the
      onset of axial muscle activity during feeding strikes. By contrast, during
      startles, jaw activity onset was nearly simultaneous with the onset of axial
      muscle activity. Stage 2 kinematics generally did not differ between the strike
      and startle; however, EMGs indicate that stage 2 movements are generated by
      different patterns of muscle activity for the two behaviors. Although strikes and
      startles are similar in their propulsive performance, they appear to be initiated
      and driven by fundamentally different motor control mechanisms. We suggest that S
      start startle behavior is mediated by a simple system of descending
      reticulospinal input to spinal neurons while the S-start strike involves a more
      complex neural circuit, allowing greater modulation of stage 1 movements while
      maintaining high stage 2 performance.

PMID- 14691102
TI  - Metabolic activity and water vapour absorption in the mealworm Tenebrio molitor
      L. (Coleoptera, Tenebrionidae): real-time measurements by two-channel
      microcalorimetry.
AB  - This work describes a new calorimetric method in which the metabolic heat
      production and water exchange rates of an insect larva are measured
      simultaneously and in real time. The experimental set-up is based on two
      independent calorimetric cells, which are perfused by a stream of air at
      controlled relative humidity (RH). The resolution for metabolic heat flow and
      water flux is 1 microW and 5 microg h(-1), respectively. The method was used to
      investigate water vapour absorption (WVA) in drought-stressed larvae of the
      common mealworm Tenebrio molitor. It was found that during exposure to a linear
      increment in RH of 3% per hour, the larvae initiated WVA upon passing a threshold
      value of 92.7+/-0.6%RH. The rate of water absorption subsequently increased to
      reach a maximal level of 86+/-6 microg h(-1), 10-15 h after passing the threshold
      value. Concomitantly, the RH in the calorimetric cell was reduced to 88.6+/-0.5%.
      The metabolic heat production of the larvae was 5-6 J h(-1) g(-1) wet mass in the
      initial part of the experiment. However, this value doubled 2-3 h prior to the
      onset of WVA, when the RH had reached 88%. This increase in metabolic heat
      production gradually tapered off over the following 24 h of WVA, during which
      time WVA remained high. Animals exposed to RH protocols that did not induce WVA
      showed no such anomalies in metabolic heat flow. This may suggest that the
      increased metabolism reflects the preparation of the WVA apparatus. Finally, the
      method was used to quantify water losses in the microgram range associated with
      wriggling and tracheal ventilation.

PMID- 14691103
TI  - The tale of the tail: limb function and locomotor mechanics in Alligator
      mississippiensis.
AB  - Crocodilians tow their large muscular tail behind them during terrestrial bouts
      when they high walk (a walking trot). Analysis of ground reaction forces in the
      American alligator (Alligator mississippiensis) revealed the consequences of tail
      dragging. Individual limb and tail ground reaction force records show that the
      hindlimbs of Alligator take on a substantial role in body mass support consistent
      with the more caudal location of its center of mass due to the presence of a
      particularly heavy tail (representing nearly 28% of total body mass).
      Furthermore, because the constant drag imposed by the tail is substantial, both
      fore- and hindlimbs in Alligator have a heightened propulsive role as a means of
      countering the net braking effect of the tail. Ground reaction forces of the
      whole body were used to assess how well Alligator was able to utilize mechanical
      energy-saving mechanisms (inverse pendulum or mass-spring). A high-walking
      Alligator recovers, on average, about 20% of its mechanical energy by inverse
      pendulum mechanics. These modest energy recovery levels are likely to be due to a
      combination of factors that may include low locomotor speed, imprecise
      coordination of contralateral limbs in the trot, frequent dragging of feet of
      protracting limbs during swing phase and, possibly, tail dragging.

PMID- 14691105
TI  - Biomineralization: on the trail of the phosphate. Part II: Phosphophoryn, the
      DMPs, and more.

PMID- 14691106
TI  - Death in the life of a tooth.
AB  - Programmed cell death (apoptosis) constitutes an important mechanism in embryonic
      development. Although there is substantial evidence for essential roles of
      apoptosis in organ shaping and controlling of cell number, the mechanisms of
      these processes are poorly understood. The regulation of cell proliferation to
      form tooth buds of the appropriate size and at the correct positions must involve
      a balance between cell division and cell death. Apoptosis has been suggested to
      play both passive and active roles in bud formation and morphogenesis and in
      reduction of the dental lamina, as well as silencing of the enamel knot signaling
      centers. The location of apoptotic cells during tooth development has been
      described and suggests their temporospatial roles. Unfortunately, there is little
      functional evidence on these roles, and the aim of this review is to highlight
      areas where apoptosis may play key roles in odontogenesis.

PMID- 14691107
TI  - The induction of gene mutations and micronuclei by oxiranes and siloranes in
      mammalian cells in vitro.
AB  - Oxiranes and siloranes are candidate molecules for the development of composite
      materials with low shrinkage. Since some of these molecules are highly reactive,
      they could lead to adverse biological effects from underlying genetic mechanisms.
      Therefore, we analyzed the formation of micronuclei (chromosomal aberrations) and
      the induction of gene mutations (HPRT assay) in mammalian cells. The numbers of
      micronuclei induced by the oxirane di(cyclohexene-epoxidemethyl)ether (Eth-Ep) at
      low concentrations (10 micro M) were about five-fold higher than controls. The
      related compound epoxy cyclohexyl methyl-epoxy cyclo-hexane carboxylate (Est-Ep)
      was less effective. The activity of diglycidylether of bisphenol A (BADGE) was
      even lower but similar to the most reactive silorane, di-3,4-epoxy
      cyclohexylmethyl-dimethyl-silane (DiMe-Sil). No induction of micronuclei was
      detected in the presence of a rat liver homogenate (S9). Est-Ep and Eth-Ep also
      induced gene mutations. Our analyses indicated low mutagenic potentials of
      siloranes; however, some oxiranes induced strong effects at two genetic
      endpoints.

PMID- 14691108
TI  - Salivary esterase activity and its association with the biodegradation of dental
      composites.
AB  - Pseudocholinesterase (PCE) and cholesterol esterase (CE) can hydrolyze
      bisphenylglycidyl dimethacrylate (bisGMA) and triethylene glycol dimethacrylate
      (TEGDMA) monomers. This study will test the hypothesis that enzyme activities
      showing CE and PCE character are found in human saliva at levels sufficient to
      hydrolyze ester-containing composites important to restorative denstistry. The
      study also seeks to ask if the active sites of CE and PCE with respect to
      composite could be inhibited. Photo-polymerized model composite resin was
      incubated in PCE and CE solutions, in the presence and absence of a specific
      esterase inhibitor, phenylmethylsulfonyl fluoride (PMSF). Incubation solutions
      were analyzed for resin degradation products by high-performance liquid
      chromatography (HPLC), UV spectroscopy, and mass spectrometry. Saliva was found
      to contain both hydrolase activities at levels that could degrade composite
      resins. PMSF inhibited the composite degradation, indicating a material
      hydrolysis mechanism similar to the enzymes' common function.

PMID- 14691109
TI  - Mesenchymal stem cells acquire characteristics of cells in the periodontal
      ligament in vitro.
AB  - Mesenchymal stem cells differentiate into multiple types of cells derived from
      mesenchyme. Periodontal ligament cells are primarily derived from mesenchyme;
      thus, we expected mesenchymal stem cells to differentiate into periodontal
      ligament. Using a combination of immunohistochemistry and in situ hybridization
      on co-cultures of mesenchymal stem cells and periodontal ligament, we observed a
      significant increase in mesenchymal stem cells' expression of osteocalcin and
      osteopontin and a significant decrease in expression of bone sialoprotein,
      characteristics of periodontal ligament in vivo. Increased osteopontin and
      osteocalcin and decreased bone sialoprotein expression was detected within 7 days
      and maintained through 21 days of co-culture. We conclude that contact or factors
      from periodontal ligament induced mesenchymal stem cells to obtain periodontal
      ligament-like characteristics. Importantly, analysis of the data suggests the
      feasibility of utilizing mesenchymal stem cells in clinical applications for
      repairing and/or regenerating periodontal tissue.

PMID- 14691110
TI  - Mouse cellular cementum is highly dependent on growth hormone status.
AB  - Cementum is known to be growth-hormone (GH)-responsive, but to what extent is
      unclear. This study examines the effects of extremes of GH status on
      cementogenesis in three lines of genetically modified mice; GH excess (giant), GH
      antagonist excess (dwarf), and GH receptor-deleted (GHR-KO) (dwarf). Age-matched
      mandibular molar tissues were processed for light microscope histology. Digital
      images of sections of first molar teeth were captured for morphometric analysis
      of lingual root cementum. Cross-sectional area of the cellular cementum was a
      sensitive guide to GH status, being reduced nearly 10-fold in GHR-KO mice, three
      fold in GH antagonist mice, and increased almost two-fold in giant mice (p <
      0.001). Cellular cementum length was similarly influenced by GH status, but to a
      lesser extent. Acellular cementum was generally unaffected. This study reveals
      cellular cementum to be a highly responsive GH target tissue, which may have
      therapeutic applications in assisting regeneration of the periodontium.

PMID- 14691111
TI  - Effects of TGF-beta on hyaluronan anabolism in fibroblasts derived from the
      synovial membrane of the rabbit temporomandibular joint.
AB  - Hyaluronan (HA) synthesis in the synovial membrane is affected by various
      chemical mediators. It is hypothesized that transforming growth factor-beta 1
      (TGF-beta 1) would be a mediator to modulate HA synthesis in cultured synovial
      membrane fibroblasts of the temporomandibular joint (TMJ). Fibroblasts were
      extracted from the TMJ synovial membrane of four-week-old Japanese white rabbits.
      The amount of HA and expression levels of HA synthase (HAS) mRNAs induced by TGF
      beta 1 treatment were analyzed by means of high-performance liquid chromatography
      and real-time polymerase chain-reaction, respectively. Both medium and large
      amounts of HA were enhanced by the stimulation of TGF-beta 1. HAS2 mRNA
      expression was enhanced 13-fold after six-hour stimulation with TGF-beta 1 (10
      ng/mL), whereas HAS3 mRNA expression was not changed significantly. These results
      suggest that TGF-beta 1 enhances the expression of HAS2 mRNA in the TMJ synovial
      membrane fibroblasts and may contribute to the production of high-molecular
      weight HA in the joint fluid.

PMID- 14691112
TI  - Genetic analysis of crown size in the first molars using SMXA recombinant inbred
      mouse strains.
AB  - Tooth crown size may be determined by both genetic and environmental factors. The
      aim of this study was to identify quantitative trait loci (QTLs) affecting dental
      crown size and determine whether there is genetic independence between upper and
      lower teeth, using SMXA recombinant inbred strains of mice. Mesiodistal and
      buccolingual crown diameters (MD and BL, respectively) of the upper and lower
      first molars (M(1) and M(1), respectively) were measured. For each trait, mean
      values of substrains showed a continuous spectrum of distribution. Genome-wide
      scan detected QTLs exceeding suggestive threshold levels for MD of M(1)
      (chromosomes 7, 13, and 17), BL of M(1) (chromosomes 8 and 13), MD of M(1)
      (chromosomes 7 and 13), and BL of M(1) (chromosomes 3 and 15). These findings
      suggest that tooth crown size is controlled by multiple genes, and that there is
      some independence of genetic control between M(1) and M(1).

PMID- 14691113
TI  - C-fos expression in rat brain nuclei following incisor tooth movement.
AB  - In the rat experimental model, molar tooth movement induced by Waldo's method is
      known to cause a temporally and spatially defined pattern of brain neuronal
      activation. Since orthodontic correction usually involves the entire dental arch,
      we used a spring-activated appliance to extend the investigation to incisors, and
      we included brain regions related to antinociception. Adjustment of the non
      activated appliance on incisors resulted in c-fos expression in the dorsal raphe,
      peri-aqueductal gray matter, and the locus coeruleus, in addition to trigeminal
      sensory subnuclei and the parabrachial nucleus, where neuronal activation has
      already been detected in previous studies on molar tooth movement. Appliance
      activation with a 70-g force resulted in a further increase in Fos-immunoreactive
      neurons in the trigeminal sensory subnucleus caudalis and in the dorsal raphe.
      This result suggests that there is a recruitment of neurons related to
      nociception and to antinociception when tooth movement is increased.

PMID- 14691114
TI  - Variation in daily masticatory muscle activity in the rabbit.
AB  - The daily use of masticatory muscles remains largely unclear, since continuous
      recordings were limited in space and time. This study's purpose was to use radio
      telemetry to examine daily muscle use and its inter- and intra-individual
      variations. A telemetric device was implanted into the rabbit masseter, and the
      transmitted signals were digitally stored for 7 days. Muscle use was analyzed by
      calculation of the total time each muscle was activated above 5, 20, and 50% of
      the day's peak activity. Rabbits (n = 6) spent only 2% of the time chewing.
      Muscles were activated up to 20% of the total time at levels exceeding 5% of peak
      activity, and only about 0.5% of the time in forceful behaviors utilizing 50% of
      maximum contraction. It can be concluded that daily muscle use remained constant
      during succeeding days, but differed significantly among muscle regions and
      individuals.

PMID- 14691115
TI  - Identification of in vivo pellicle constituents by analysis of serum immune
      responses.
AB  - Human acquired enamel pellicle is composed of molecules that selectively adsorb
      from saliva onto tooth surfaces and provides a protective interface between the
      tooth enamel and the oral environment. To identify the micro-amounts of
      components present in pellicle, we immunized mice with in vivo-formed human
      acquired enamel pellicle and analyzed the serum immune responses. Selective
      reactivities of the serum (OD > 1.0 above background) against albumin, amylase,
      carbonic anhydrase II, sIgA, IgG, IgM, lactoferrin, lysozyme, proline-rich
      proteins, statherin, histatin 1, and mucous glycoprotein 1 were observed. We
      further confirmed the presence of proline-rich proteins, lactoferrin, lysozyme,
      and carbonic anhydrase II by probing in vivo pellicle with specific polyclonal
      anti-sera. The polyclonal antibody approach provided a powerful method for the
      identification of various pellicle proteins, including some which show mineral
      homeostasis or antimicrobial activity.

PMID- 14691116
TI  - Non-primate lentiviral vector administration in the TMJ.
AB  - Gene therapy is emerging as a novel treatment method for the management of
      temporomandibular joint disorders. The aim of this investigation was to study the
      effects of lentiviral vectors on the temporomandibular joint. Consequently, we
      injected into the articular joint space a defective feline immunodeficiency virus
      capable of infecting dividing as well as terminally differentiated cells with the
      reporter gene lacZ, the expression of which was studied by means of PCR, X-gal
      histochemistry, and beta-galactosidase immunocytochemistry. Our results showed
      successful transduction of hard and soft tissues of the temporomandibular joint.
      Interestingly, a subset of primary sensory neurons of the ipsilateral trigeminal
      ganglion also stained positive for the reporter gene, presumably following uptake
      of the lentiviral vector by peripheral nerve fibers and retrograde transport to
      the nucleus. These findings suggest that lentiviral vectors can potentially serve
      as a platform for the transfer of anti-nociceptive genes for the management of
      temporomandibular joint pain.

PMID- 14691117
TI  - In situ effect of frequent sucrose exposure on enamel demineralization and on
      plaque composition after APF application and F dentifrice use.
AB  - Since the effect of the combination of methods of fluoride use on enamel
      demineralization and on plaque composition is not clearly established, this study
      examined the effect of the combination of acidulated phosphate fluoride (APF)
      application and F dentifrice on enamel demineralization and on plaque
      composition. In this crossover study, 16 volunteers, wearing a palatal appliance
      containing bovine enamel blocks, were subjected to 4 treatment groups: non
      fluoridated dentifrice (PD), FD, APF+PD, and APF+FD. The APF was applied to the
      enamel before the 14-day experimental period. During the experimental period,
      test dentifrices were applied 3x/day, and a 20% sucrose solution was applied 4x
      and 8x/day by being dripped on the blocks. Although APF application was able
      either to increase F concentration in plaque or to reduce the % of mutans
      streptococci, its combination with F dentifrice use neither reduced enamel
      mineral loss nor changed any other measured plaque variable with respect to the
      FD group alone.

PMID- 14691118
TI  - Is fluoride concentration in dentin and enamel a good indicator of dental
      fluorosis?
AB  - Despite some studies correlating dental fluorosis (DF) and fluoride (F)
      concentration in dental enamel, no information is available about DF and dentin F
      concentration. Our objective was to determine the correlation between teeth F
      concentration and DF severity in unerupted human 3rd molars, and the correlation
      between dentin and enamel F concentrations in the same tooth. Ninety-nine 3rd
      molars were studied-53 from Fortaleza, Brazil (F water, 0.7 ppm), 22 from Toronto
      (1.0 ppm), and 24 from Montreal (0.2 ppm). DF severity was evaluated according to
      the Thylstrup-Fejerskov Index, while F concentration was analyzed by Instrumental
      Neutron Activation Analysis. DF severity varied between TF0 and TF4, while F
      concentration ranged between 39 and 550 ppm in enamel and 101 and 860 ppm in
      dentin. Our results showed correlation between dentin F concentration and DF
      (r(S) = 0.316, p = 0.001), but no correlation between enamel F concentration and
      DF (r(S) = 0.154, p = 0.133). No correlation was observed between dentin and
      enamel F concentrations in the same tooth (r(S) = 0.064, p = 0.536).

PMID- 14691119
TI  - Study on the organoleptic intensity scale for measuring oral malodor.
AB  - The 0-5 organoleptic scale is used widely in breath research and in trials to
      measure the efficacy of anti-odor agents. However, the precise relationship
      between odor scores and gas concentrations of target odorants is unknown. The
      purpose of this study was to relate mean organoleptic scores from odor judges (n
      = 7) for pure odorants (n = 8) representative of those found in oral malodor.
      Judges used a common 0-5 scale to report the odor intensity of sample sets in
      random order of concentration. Regression analysis of data showed that odor score
      was proportional to the log concentration of odorant, and comparison of slopes
      showed H(2)S to be the most significant in terms of odor power. Detection
      thresholds (mol.dm(-3)) were: Skatole (7.2 x 10(-13)) < methylmercaptan (1.0 x
      10(-11)) < trimethylamine (1.8 x 10(-11)) < isovalerate (1.8 x 10(-11)) <
      butyrate (2.3 x 10(-10)) < hydrogen sulphide (6.4 x 10(-10)) < putrescine (9.1 x
      10(-10)) < dimethyl disulphide (5.9 x 10(-8)). The study demonstrates the
      exponential nature of the olfactory response and shows that any single compound's
      contribution to malodor depends on odor power and threshold in addition to
      concentration.

PMID- 14691120
TI  - Pathologic variables and recurrence rates as related to obesity and race in men
      with prostate cancer undergoing radical prostatectomy.
AB  - PURPOSE: To determine if obesity is associated with higher prostate specific
      antigen recurrence rates after radical prostatectomy (RP), and to explore racial
      differences in body mass index (BMI) as a potential explanation for the disparity
      in outcome between black and white men. PATIENTS AND METHODS: A retrospective,
      multi-institutional pooled analysis of 3,162 men undergoing RP was conducted at
      nine US military medical centers between 1987 and 2002. Patients were initially
      categorized as obese (BMI > or = 30 kg/m(2)), overweight (BMI 25 to 30 kg/m(2)),
      or normal (BMI < or = 25 kg/m(2)). For analysis, normal and overweight groups
      were combined (BMI < 30 kg/m(2)) and compared with the obese group (BMI > or = 30
      kg/m(2)) with regard to biochemical recurrence (prostate-specific antigen > or =
      0.2 ng/mL) after RP. RESULTS: Of 3,162 patients, 600 (19.0%) were obese and 2,562
      (81%) were not obese. BMI was an independent predictor of higher Gleason grade
      cancer (P <.001) and was associated with a higher risk of biochemical recurrence
      (P =.027). Blacks had higher BMI (P <.001) and higher recurrence rates (P =.003)
      than whites. Both BMI (P =.028) and black race (P =.002) predicted higher
      prostate specific antigen recurrence rates. In multivariate analysis of race,
      BMI, and pathologic factors, black race (P =.021) remained a significant
      independent predictor of recurrence. CONCLUSION: Obesity is associated with
      higher grade cancer and higher recurrence rates after RP. Black men have higher
      recurrence rates and greater BMI than white men. These findings support the
      hypothesis that obesity is associated with progression of latent to clinically
      significant prostate cancer (PC) and suggest that BMI may account, in part, for
      the racial variability in PC risk.

PMID- 14691121
TI  - Are patients diagnosed with breast cancer before age 50 years ever cured?
AB  - PURPOSE: Breast cancer diagnosed before the age of 50 years has become a common
      disease in many developed countries. Although average remaining life expectancy
      in the affected age groups is usually several decades, data regarding survival
      perspectives beyond 10 to 20 years after diagnosis are sparse. The aim of this
      study was to assess long-term survival in a large population-based sample of
      patients diagnosed with breast cancer before age 50 years. PATIENTS AND METHODS:
      Relative survival within up to 40 years after diagnosis was assessed for cohorts
      of women diagnosed with breast cancer before age 50 years and notified to the
      nationwide Finnish Cancer Registry within various time intervals since 1953. In
      addition, up-to-date estimates of 40-year relative survival were obtained by
      exclusively looking at the survival experience of breast cancer patients in
      recent years (1993 to 1999) using period analysis, a new method of survival
      analysis. RESULTS: Prognosis of patients diagnosed with breast cancer before age
      50 years has considerably improved during the past decades. According to the
      latest estimates from period analysis, cumulative 40-year relative survival is
      now approximately 43% for all cancers combined, 57% for localized cancers, and
      24% for cancers with regional tumor spread. Nevertheless, patients diagnosed with
      breast cancer before age 50 years continue to have increased mortality throughout
      at least four decades after diagnosis. This applies even if breast cancer is
      diagnosed in a localized stage and in the absence of a second primary breast
      cancer. CONCLUSION: Despite major improvement in prognosis over time, breast
      cancer occurring among patients who are younger than 50 years remains a chronic
      disease that affects prognosis for decades.

PMID- 14691122
TI  - Impact of obesity on biochemical control after radical prostatectomy for
      clinically localized prostate cancer: a report by the Shared Equal Access
      Regional Cancer Hospital database study group.
AB  - PURPOSE: Given the limited information regarding the impact of obesity on
      treatment outcomes for prostate cancer, we sought to examine the relationship
      between body mass index (BMI) and cancer control after radical prostatectomy
      (RP). PATIENTS AND METHODS: We compared clinicopathologic and biochemical outcome
      information across BMI groups from 1,106 men treated with RP between 1988 and
      2002. Multivariate analysis was used to determine if BMI significantly predicted
      adverse pathology or biochemical recurrence. RESULTS: Obesity was related to year
      of surgery (P <.001) and race (P <.001), with black men having the highest
      obesity rates. Obese patients had higher biopsy and pathologic grade tumors (P
      <.001). On multivariate analysis, BMI > or = 35 kg/m(2) was associated with a
      trend for higher rates of positive surgical margins (P =.008). Overweight
      patients (BMI, 25 to 30 kg/m(2)) had a significantly decreased risk of seminal
      vesicle invasion (P =.039). After controlling for all preoperative clinical
      variables including year of surgery, BMI > or = 35 kg/m(2) significantly
      predicted biochemical failure after RP (P =.002). After controlling for surgical
      margin status, BMI > or = 35 kg/m(2) remained a significant predictor of
      biochemical failure (P =.012). There was a trend for BMI > or = 35 kg/m(2) to be
      associated with higher failure rates than BMI between 30 and 35 kg/m(2) (P
      =.053). CONCLUSION: The percentage of obese men undergoing RP in our data set
      doubled in the last 10 years. Obesity was associated with higher-grade tumors, a
      trend toward increased risk of positive surgical margins, and higher biochemical
      failure rates among men treated with RP. A BMI > or = 35 kg/m(2) was associated
      with a higher risk of failure than a BMI between 30 and 35 kg/m(2).

PMID- 14691123
TI  - Immunopharmacologic analysis of an autologous, hapten-modified human melanoma
      vaccine.
AB  - PURPOSE: We have previously reported a clinical trial of a human cancer vaccine
      consisting of autologous tumor cells modified with the hapten, dinitrophenyl
      (DNP), in patients with clinical stage III melanoma. Here we present a follow-up
      report expanded to 214 patients with 5-year follow-up. PATIENTS AND METHODS: Two
      hundred fourteen patients with clinical stage III melanoma (117 patients with
      stage IIIC and 97 patients with stage IIIB) who were melanoma-free after standard
      lymphadenectomy were treated with multiple intradermal injections of autologous,
      DNP-modified vaccine mixed with bacille Calmette-Guerin. Four vaccine dosage
      schedules were tested sequentially, all of which included low-dose
      cyclophosphamide. Patients were tested for delayed-type hypersensitivity (DTH) to
      autologous melanoma cells, both DNP-modified and unmodified, and to control
      materials. RESULTS: The 5-year overall survival (OS) rate of the 214 patients was
      44%. DTH responses to unmodified autologous melanoma were induced in 47% of
      patients. The OS of this DTH-positive group was double that of DTH-negative
      patients (59.3% v 29.3%; P <.001). In contrast, positive DTH responses to DNP
      modified autologous melanoma cells and to purified protein derivative developed
      in almost all patients but did not affect OS. Surprisingly, the OS after relapse
      was also significantly longer in patients who developed positive DTH to
      unmodified tumor cells (25.2% v 12.3%; P <.001). Finally, the development of DTH
      was dependent on the schedule of administration of the vaccine, specifically, the
      timing of an induction dose administered at the beginning of the treatment
      program. CONCLUSION: This study underscores the importance of the
      immunopharmacology of the autologous, DNP-modified vaccine and may be relevant to
      other cancer vaccine technologies.

PMID- 14691124
TI  - Treatment with granulocyte colony-stimulating factor after allogeneic bone marrow
      transplantation for acute leukemia increases the risk of graft-versus-host
      disease and death: a study from the Acute Leukemia Working Party of the European
      Group for Blood and Marrow Transplantation.
AB  - PURPOSE: Granulocyte colony-stimulating factor (G-CSF) is given after bone marrow
      transplantation (BMT) to shorten the neutropenic phase. Its effects have not been
      evaluated in a large patient population. PATIENTS AND METHODS: We studied 1,789
      patients with acute leukemia receiving BMT and 434 patients receiving peripheral
      blood stem cells (PBSCs) from HLA-identical siblings from 1992 to 2002 and
      reported the findings to the European Group for Blood and Marrow Transplantation.
      Among the BMT and PBSC patients, 501 (28%) and 175 (40%), respectively, were
      treated with G-CSF during the first 14 days after the transplantation. The
      outcome variables were entered into a Cox proportional hazards model. RESULTS:
      BMT and PBSC patients treated with G-CSF had a faster engraftment of absolute
      neutrophils greater than 0.5 x 10(9)/L (P <.01), but platelet engraftment ( > 50
      x 10(9)/L) was slower (P <.001). In the BMT patients, acute graft-versus-host
      disease (GVHD) grades II to IV was 50% +/- 5% (+/- 95% CI) in the G-CSF group
      versus 39% +/- 3% in the controls (relative risk [RR], 1.33; P =.007, in the
      multivariate analysis). The incidence of chronic GVHD was also increased (RR,
      1.29; P =.03). G-CSF was associated with an increase in transplantation-related
      mortality (TRM; RR, 1.73; P =.00016) and had no effect on relapse but reduced
      survival (RR, 0.59; P <.0001) and leukemia-free survival rates (LFS; RR, 0.64; P
      =.0003). No such effects of G-CSF were seen in patients receiving PBSC.
      CONCLUSION: After BMT, platelet engraftment was delayed, and GVHD and TRM were
      increased. Survival and LFS were reduced. This suggests that G-CSF should not be
      given shortly after BMT.

PMID- 14691125
TI  - American Society of Clinical Oncology treatment of unresectable non-small-cell
      lung cancer guideline: update 2003.

PMID- 14691126
TI  - When will melanoma vaccines be proven effective?

PMID- 14691127
TI  - Use of granulocyte colony-stimulating factor following hematopoietic cell
      transplantation: does haste make waste?

PMID- 14691128
TI  - Do estimates of long-term survival tell us whether patients diagnosed with breast
      cancer before age 50 years are ever cured?

PMID- 14691129
TI  - The "skinny" on obesity and prostate cancer prognosis.

PMID- 14691130
TI  - Cup-ling oskar RNA localization and translational control.
AB  - RNA localization and spatially restricted translational control can serve to
      deploy specific proteins to particular places within a cell. oskar (osk) RNA is a
      key initiatior of posterior patterning and germ cell specification in Drosophila,
      and its localization and translation are under elaborate control. In this issue,
      Wilhelm et al. (2003) show that the protein Cup both promotes osk localization
      and participates in repressing translation of unlocalized osk.

PMID- 14691131
TI  - Myosin V and the endoplasmic reticulum: the connection grows.
AB  - In this issue, Estrada et al. (2003) provide new and important insights into how
      the endoplasmic reticulum (ER) of budding yeast cells is inherited. Together with
      other studies in plant and animal cells, the results of Estrada et al. (2003)
      support the idea that myosin V acts as a universal motor for the transport of ER
      membranes.

PMID- 14691132
TI  - Cup is an eIF4E binding protein required for both the translational repression of
      oskar and the recruitment of Barentsz.
AB  - In Drosophila oocytes, precise localization of the posterior determinant, Oskar,
      is required for posterior patterning. This precision is accomplished by a
      localization-dependent translational control mechanism that ensures translation
      of only correctly localized oskar transcripts. Although progress has been made in
      identifying localization factors and translational repressors of oskar, none of
      the known components of the oskar complex is required for both processes. Here,
      we report the identification of Cup as a novel component of the oskar RNP
      complex. cup is required for oskar mRNA localization and is necessary to recruit
      the plus end-directed microtubule transport factor Barentsz to the complex.
      Surprisingly, Cup is also required to repress the translation of oskar.
      Furthermore, eukaryotic initiation factor 4E (eIF4E) is localized within the
      oocyte in a cup-dependent manner and binds directly to Cup in vitro. Thus, Cup is
      a translational repressor of oskar that is required to assemble the oskar mRNA
      localization machinery. We propose that Cup coordinates localization with
      translation.

PMID- 14691133
TI  - A role for cytoplasmic dynein and LIS1 in directed cell movement.
AB  - Cytoplasmic dynein has been implicated in numerous aspects of intracellular
      movement. We recently found dynein inhibitors to interfere with the reorientation
      of the microtubule cytoskeleton during healing of wounded NIH3T3 cell monolayers.
      We now find that dynein and its regulators dynactin and LIS1 localize to the
      leading cell cortex during this process. In the presence of serum, bright diffuse
      staining was observed in regions of active ruffling. This pattern was abolished
      by cytochalasin D, and was not observed in cells treated with lysophosphatidic
      acid, conditions which allow microtubule reorientation but not forward cell
      movement. Under the same conditions, using total internal reflection fluorescence
      microscopy, clear punctate dynein/dynactin containing structures were observed
      along the sides and at the tips of microtubules at the leading edge.
      Overexpression of dominant negative dynactin and LIS1 cDNAs or injection of
      antidynein antibody interfered with the rate of cell migration. Together, these
      results implicate a leading edge cortical pool of dynein in both early and
      persistent steps in directed cell movement.

PMID- 14691135
TI  - Mathematical model of the morphogenesis checkpoint in budding yeast.
AB  - The morphogenesis checkpoint in budding yeast delays progression through the cell
      cycle in response to stimuli that prevent bud formation. Central to the
      checkpoint mechanism is Swe1 kinase: normally inactive, its activation halts cell
      cycle progression in G2. We propose a molecular network for Swe1 control, based
      on published observations of budding yeast and analogous control signals in
      fission yeast. The proposed Swe1 network is merged with a model of cyclin
      dependent kinase regulation, converted into a set of differential equations and
      studied by numerical simulation. The simulations accurately reproduce the
      phenotypes of a dozen checkpoint mutants. Among other predictions, the model
      attributes a new role to Hsl1, a kinase known to play a role in Swe1 degradation:
      Hsl1 must also be indirectly responsible for potent inhibition of Swe1 activity.
      The model supports the idea that the morphogenesis checkpoint, like other
      checkpoints, raises the cell size threshold for progression from one phase of the
      cell cycle to the next.

PMID- 14691134
TI  - Spindle checkpoint proteins Mad1 and Mad2 are required for cytostatic factor
      mediated metaphase arrest.
AB  - In cells containing disrupted spindles, the spindle assembly checkpoint arrests
      the cell cycle in metaphase. The budding uninhibited by benzimidazole (Bub) 1,
      mitotic arrest-deficient (Mad) 1, and Mad2 proteins promote this checkpoint
      through sustained inhibition of the anaphase-promoting complex/cyclosome.
      Vertebrate oocytes undergoing meiotic maturation arrest in metaphase of meiosis
      II due to a cytoplasmic activity termed cytostatic factor (CSF), which appears
      not to be regulated by spindle dynamics. Here, we show that microinjection of
      Mad1 or Mad2 protein into early Xenopus laevis embryos causes metaphase arrest
      like that caused by Mos. Microinjection of antibodies to either Mad1 or Mad2 into
      maturing oocytes blocks the establishment of CSF arrest in meiosis II, and
      immunodepletion of either protein blocked the establishment of CSF arrest by Mos
      in egg extracts. A Mad2 mutant unable to oligomerize (Mad2 R133A) did not cause
      cell cycle arrest in blastomeres or in egg extracts. Once CSF arrest has been
      established, maintenance of metaphase arrest requires Mad1, but not Mad2 or Bub1.
      These results suggest a model in which CSF arrest by Mos is mediated by the Mad1
      and Mad2 proteins in a manner distinct from the spindle checkpoint.

PMID- 14691136
TI  - Myo4p and She3p are required for cortical ER inheritance in Saccharomyces
      cerevisiae.
AB  - Myo4p is a nonessential type V myosin required for the bud tip localization of
      ASH1 and IST2 mRNA. These mRNAs associate with Myo4p via the She2p and She3p
      proteins. She3p is an adaptor protein that links Myo4p to its cargo. She2p binds
      to ASH1 and IST2 mRNA, while She3p binds to both She2p and Myo4p. Here we show
      that Myo4p and She3p, but not She2p, are required for the inheritance of cortical
      ER in the budding yeast Saccharomyces cerevisiae. Consistent with this
      observation, we find that cortical ER inheritance is independent of mRNA
      transport. Cortical ER is a dynamic network that forms cytoplasmic tubular
      connections to the nuclear envelope. ER tubules failed to grow when actin
      polymerization was blocked with the drug latrunculin A (Lat-A). Additionally, a
      reduction in the number of cytoplasmic ER tubules was observed in Lat-A-treated
      and myo4Delta cells. Our results suggest that Myo4p and She3p facilitate the
      growth and orientation of ER tubules.

PMID- 14691137
TI  - Recognition of dileucine-based sorting signals from HIV-1 Nef and LIMP-II by the
      AP-1 gamma-sigma1 and AP-3 delta-sigma3 hemicomplexes.
AB  - The sorting of transmembrane proteins to endosomes and lysosomes is mediated by
      signals present in the cytosolic tails of the proteins. A subset of these signals
      conform to the [DE]XXXL[LI] consensus motif and mediate sorting via interactions
      with heterotetrameric adaptor protein (AP) complexes. However, the identity of
      the AP subunits that recognize these signals remains controversial. We have used
      a yeast three-hybrid assay to demonstrate that [DE]XXXL[LI]-type signals from the
      human immunodeficiency virus negative factor protein and the lysosomal integral
      membrane protein II interact with combinations of the gamma and sigma1 subunits
      of AP-1 and the delta and sigma3 subunits of AP-3, but not the analogous
      combinations of AP-2 and AP-4 subunits. The sequence requirements for these
      interactions are similar to those for binding to the whole AP complexes in vitro
      and for function of the signals in vivo. These observations reveal a novel mode
      of recognition of sorting signals involving the gamma/delta and sigma subunits of
      AP-1 and AP-3.

PMID- 14691138
TI  - TGFbeta3 signaling activates transcription of the LEF1 gene to induce epithelial
      mesenchymal transformation during mouse palate development.
AB  - Epithelial mesenchymal transformation (EMT) of the medial edge epithelial (MEE)
      seam creates palatal confluence. This work aims to elucidate the molecular
      mechanisms by which TGFbeta3 brings about palatal seam EMT. We collected mRNA for
      PCR analysis from individual transforming MEE cells by laser microdissection
      techniques and demonstrated that TGFbeta3 stimulates lymphoid-enhancing factor 1
      (LEF1) mRNA synthesis in MEE cells. We show with antisense beta-catenin
      oligonucleotides that up-regulated LEF1 is not activated by beta-catenin in
      palate EMT. We ruled out other TGFbeta3 targets, such as RhoA and MEK1/2
      pathways, and we present evidence using dominant-negative Smad4 and dominant
      negative LEF1 showing that TGFbeta3 uses Smads both to up-regulate synthesis of
      LEF1 and to activate LEF1 transcription during induction of palatal EMT. When
      phospho-Smad2 and Smad4 are present in the nucleus, LEF1 is activated without
      beta-catenin. Our paper is the first to show that the Smad2,4/LEF1 complex
      replaces beta-catenin/LEF1 during activation of EMT in vivo by TGFbeta3.

PMID- 14691139
TI  - Multiple EphB receptor tyrosine kinases shape dendritic spines in the
      hippocampus.
AB  - Here, using a genetic approach, we dissect the roles of EphB receptor tyrosine
      kinases in dendritic spine development. Analysis of EphB1, EphB2, and EphB3
      double and triple mutant mice lacking these receptors in different combinations
      indicates that all three, although to varying degrees, are involved in dendritic
      spine morphogenesis and synapse formation in the hippocampus. Hippocampal neurons
      lacking EphB expression fail to form dendritic spines in vitro and they develop
      abnormal spines in vivo. Defective spine formation in the mutants is associated
      with a drastic reduction in excitatory glutamatergic synapses and the clustering
      of NMDA and AMPA receptors. We show further that a kinase-defective, truncating
      mutation in EphB2 also results in abnormal spine development and that ephrin-B2
      mediated activation of the EphB receptors accelerates dendritic spine
      development. These results indicate EphB receptor cell autonomous forward
      signaling is responsible for dendritic spine formation and synaptic maturation in
      hippocampal neurons.

PMID- 14691140
TI  - Isoform-specific insulin receptor signaling involves different plasma membrane
      domains.
AB  - In pancreatic beta-cells, insulin selectively up-regulates the transcription of
      its own gene and that of the glucokinase gene by signaling through the two
      isoforms of the insulin receptor, i.e., A-type (Ex11-) and B-type (Ex11+), using
      different signaling pathways. However, the molecular mechanism(s) that allows the
      discrete activation of signaling cascades via the two receptor isoforms remains
      unclear. Here we show that activation of the insulin promoter via A-type and of
      the glucokinase promoter via B-type insulin receptor is not dependent on receptor
      isoform-specific differences in internalization but on the different localization
      of the receptor types in the plasma membrane. Our data demonstrate that
      localization and function of the two receptor types depend on the 12-amino acid
      string encoded by exon 11, which acts as a sorting signal rather than as a
      physical spacer. Moreover, our data suggest that selective activation of the
      insulin and glucokinase promoters occurs by signaling from noncaveolae lipid
      rafts that are differently sensitive toward cholesterol depletion.

PMID- 14691141
TI  - Tyrosine phosphorylation of type Igamma phosphatidylinositol phosphate kinase by
      Src regulates an integrin-talin switch.
AB  - Engagement of integrin receptors with the extracellular matrix induces the
      formation of focal adhesions (FAs). Dynamic regulation of FAs is necessary for
      cells to polarize and migrate. Key interactions between FA scaffolding and
      signaling proteins are dependent on tyrosine phosphorylation. However, the
      precise role of tyrosine phosphorylation in FA development and maturation is
      poorly defined. Here, we show that phosphorylation of type Igamma
      phosphatidylinositol phosphate kinase (PIPKIgamma661) on tyrosine 644 (Y644) is
      critical for its interaction with talin, and consequently, localization to FAs.
      PIPKIgamma661 is specifically phosphorylated on Y644 by Src. Phosphorylation is
      regulated by focal adhesion kinase, which enhances the association between
      PIPKIgamma661 and Src. The phosphorylation of Y644 results in an approximately 15
      fold increase in binding affinity to the talin head domain and blocks beta
      integrin binding to talin. This defines a novel phosphotyrosine-binding site on
      the talin F3 domain and a "molecular switch" for talin binding between
      PIPKIgamma661 and beta-integrin that may regulate dynamic FA turnover.

PMID- 14691142
TI  - alpha3beta1 integrin-CD151, a component of the cadherin-catenin complex,
      regulates PTPmu expression and cell-cell adhesion.
AB  - The beta1 family of integrins has been primarily studied as a set of receptors
      for the extracellular matrix. In this paper, we define a novel role for
      alpha3beta1 integrin in association with the tetraspanin CD151 as a component of
      a cell-cell adhesion complex in epithelial cells that directly stimulates
      cadherin-mediated adhesion. The integrin-tetraspanin complex affects epithelial
      cell-cell adhesion at the level of gene expression both by regulating expression
      of PTPmu and by organizing a multimolecular complex containing PKCbetaII, RACK1,
      PTPmu, beta-catenin, and E-cadherin. These findings demonstrate how integrin
      based signaling can regulate complex biological responses at multiple levels to
      determine cell morphology and behavior.

PMID- 14691143
TI  - Latent TGF-beta binding protein LTBP-2 decreases fibroblast adhesion to
      fibronectin.
AB  - We have analyzed the effects of latent TGF-beta binding protein 2 (LTBP-2) and
      its fragments on lung fibroblast adhesion. Quantitative cell adhesion assays
      indicated that fibroblasts do not adhere to full-length LTBP-2. Interestingly,
      LTBP-2 had dominant disrupting effects on the morphology of fibroblasts adhering
      to fibronectin (FN). Fibroblasts plated on LTBP-2 and FN substratum exhibited
      less adherent morphology and displayed clearly decreased actin stress fibers than
      cells plated on FN. These cells formed, instead, extensive membrane ruffles. LTBP
      2 had no effects on cells adhering to collagen type I. Fibroblasts adhered weakly
      to the NH2-terminal fragment of LTBP-2. Unlike FN, this fragment did not augment
      actin stress fiber formation. Interestingly, the adhesion-mediating and
      cytoskeleton-disrupting effects were localized to the same NH2-terminal proline
      rich region of LTBP-2. LTBP-2 and its antiadhesive fragment bound to FN in vitro,
      and the antiadhesive fragment associated with the extracellular matrix FN
      fibrils. These observations reveal a potentially important role for LTBP-2 as an
      antiadhesive matrix component.

PMID- 14691144
TI  - VEGF is a chemoattractant for FGF-2-stimulated neural progenitors.
AB  - Migration of undifferentiated neural progenitors is critical for the development
      and repair of the nervous system. However, the mechanisms and factors that
      regulate migration are not well understood. Here, we show that vascular
      endothelial growth factor (VEGF)-A, a major angiogenic factor, guides the
      directed migration of neural progenitors that do not display antigenic markers
      for neuron- or glia-restricted precursor cells. We demonstrate that progenitor
      cells express both VEGF receptor (VEGFR) 1 and VEGFR2, but signaling through
      VEGFR2 specifically mediates the chemotactic effect of VEGF. The expression of
      VEGFRs and the chemotaxis of progenitors in response to VEGF require the presence
      of fibroblast growth factor 2. These results demonstrate that VEGF is an
      attractive guidance cue for the migration of undifferentiated neural progenitors
      and offer a mechanistic link between neurogenesis and angiogenesis in the nervous
      system.

PMID- 14691145
TI  - Autocrine laminin-5 ligates alpha6beta4 integrin and activates RAC and NFkappaB
      to mediate anchorage-independent survival of mammary tumors.
AB  - Invasive carcinomas survive and evade apoptosis despite the absence of an
      exogenous basement membrane. How epithelial tumors acquire anchorage independence
      for survival remains poorly defined. Epithelial tumors often secrete abundant
      amounts of the extracellular matrix protein laminin 5 (LM-5) and frequently
      express alpha6beta4 integrin. Here, we show that autocrine LM-5 mediates
      anchorage-independent survival in breast tumors through ligation of a wild-type,
      but not a cytoplasmic tail-truncated alpha6beta4 integrin. alpha6beta4 integrin
      does not mediate tumor survival through activation of ERK or AKT. Instead, the
      cytoplasmic tail of beta4 integrin is necessary for basal and epidermal growth
      factor-induced RAC activity, and RAC mediates tumor survival. Indeed, a
      constitutively active RAC sustains the viability of mammary tumors lacking
      functional beta1 and beta4 integrin through activation of NFkappaB, and
      overexpression of NFkappaB p65 mediates anchorage-independent survival of
      nonmalignant mammary epithelial cells. Therefore, epithelial tumors could survive
      in the absence of exogenous basement membrane through autocrine LM-5-alpha6beta4
      integrin-RAC-NFkappaB signaling.

PMID- 14691146
TI  - Microcirculation and tumor-infiltrating macrophages in choroidal and ciliary body
      melanoma and corresponding metastases.
AB  - PURPOSE: To investigate the relationship between progression to hepatic
      metastasis and tumor-infiltrating macrophages and microcirculation attributes in
      uveal melanoma, a cancer that almost invariably disseminates hematogenously to
      the liver. METHODS: A cross-sectional histopathologic analysis of 48 hepatic
      metastases and corresponding primary choroidal and ciliary body melanomas was
      conducted, by using statistical tests appropriate for paired data. Main outcome
      measures were the number and type of CD68-immunopositive, tumor-infiltrating
      macrophages, extravascular matrix loops and networks identified with periodic
      acid-Schiff stain, and microvascular density (MVD) counted as the number of
      discrete structures labeled by monoclonal antibody QBEND/10 to the CD34 epitope.
      RESULTS: Hepatic metastases had a significantly lower grade of pigmentation (P <
      0.0001), more frequent epithelioid cells (P = 0.0027), more intermediate and
      dendritic types of CD68-immunopositive macrophages than round ones (P = 0.0031),
      and a higher MVD (median difference, 15 counts more/0.313 mm2, P = 0.0003) than
      the primary uveal melanomas that spawned the metastases. The frequency of tumors
      with extravascular loops and networks did not increase on metastasizing. The
      survival of the patient after diagnosis of disseminated disease tended to be
      shorter if hepatic metastases had a high MVD (P = 0.098), adjusting for the size
      of the specimen. CONCLUSIONS: Of the markers studied, the presence of epithelioid
      cells and MVD most closely parallel progression of uveal melanoma from primary
      tumor to metastasis. These two tumor characteristics may be interrelated, and
      high MVD may help to predict survival after detection of hepatic metastases. The
      results also suggest that the grade of pigmentation and morphologic type of tumor
      infiltrating macrophages are interrelated.

PMID- 14691147
TI  - VEGF and KDR gene expression during human embryonic and fetal eye development.
AB  - PURPOSE: It is important to understand the development of the normal retinal
      vascular system, because it may provide clues for understanding the mechanisms
      underlying the neovascularization associated with several retinopathies of
      infancy and adulthood. However, little is known about normal human ocular
      vascularization. VEGF is a key growth factor during vascular development and one
      of its receptors, KDR, plays a pivotal role in endothelial cell proliferation and
      differentiation. The purpose of this study was to analyze VEGF and KDR gene
      expression patterns during the development of the human eye during the embryonic
      and fetal stages. METHODS: The gene expression of VEGF and KDR was analyzed by in
      situ hybridization in 7-week-old embryos and in 10- and 18-week-old fetuses. In
      addition, we performed VEGF and KDR immunohistochemistry experiments on 18-week
      old fetus tissue sections. RESULTS: These results clearly demonstrated that the
      levels of VEGF and KDR transcripts are correlated during the normal development
      of the ocular vasculature in humans. The complementarity between the patterns of
      VEGF and KDR during the early stages of development suggests that VEGF-KDR
      interactions play a major role in the formation and regression of the hyaloid
      vascular system (HVS) and in the development of the choriocapillaris. In later
      stages (i.e., 18-weeks-old fetuses), the expression of KDR seems to be linked to
      the development of the retinal vascular system. VEGF and KDR transcripts were
      unexpectedly detected in some nonvascular tissues-that is, in the cornea and in
      the retina before the development of the retinal vascular system. CONCLUSIONS:
      The expression of VEGF and KDR correlates highly with the normal ocular
      vascularization in humans, but VEGF may also be necessary for nonvascular retinal
      developmental functions, especially for the coordination of neural retinal
      development and the preliminary steps of the establishment of the definitive
      stable retinal vasculature.

PMID- 14691148
TI  - Absence of functional and structural abnormalities associated with expression of
      EGFP in the retina.
AB  - PURPOSE: The present study was undertaken to evaluate the effect of uniform EGFP
      expression on retinal morphology and function. METHODS: Electroretinography (ERG)
      was used to evaluate the recovery of scotopic a- and b-wave amplitudes after a
      single 137-cd.sec/m2 flash exposure. The cellular distribution of enhanced green
      fluorescent protein (EGFP) in the retina and its effect on retinal morphology
      were evaluated by fluorescence microscopy and histology, respectively. To
      evaluate its effect on retinal sensitivity to light, EGFP-expressing and control
      mice were exposed to constant light for 76 hours (3500 lux), and eyes were
      assessed functionally and structurally at 3 weeks after light exposure. RESULTS:
      Fluorescence microscopy showed a pronounced EGFP expression in the photoreceptor
      cell bodies and inner segments. ERG analysis revealed no significant differences
      in either a- or b-wave amplitudes or recovery between EGFP(+/-) and control mice
      under dark- or light-adapted conditions. Histologic assessment at as late as 4
      months of age showed no difference in retinal morphology or photoreceptor nuclei
      count in EGFP(+/-) mice when compared with nontransgenic littermates. In
      addition, evaluation of animals, 3 weeks after constant light exposure, showed no
      difference between ERG amplitudes, recovery of the scotopic ERG response, or
      retinal morphology between EGFP(+/-) mice and control animals. CONCLUSIONS:
      Functional and morphologic evidence shows that long-term, high, uniform levels of
      EGFP expression have no deleterious effect on the mouse retina. This data
      demonstrates the safety of EGFP use as an indicator of viral transduction in
      retinal gene therapy.

PMID- 14691149
TI  - Catalase and peroxiredoxin 5 protect Xenopus embryos against alcohol-induced
      ocular anomalies.
AB  - PURPOSE: To study the molecular mechanisms underlying alcohol-induced ocular
      anomalies in Xenopus embryos. METHODS: Xenopus embryos were exposed to various
      concentrations (0.1%-0.5%) of alcohol, and the subsequent effects in eye
      development and in eye marker gene expression were determined. To investigate the
      role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in
      fetal alcohol syndrome (FAS)-associated ocular injury, two antioxidant enzymes,
      catalase and peroxiredoxin 5, were overexpressed in the two blastomeres of the
      two-cell stage Xenopus embryos. RESULTS: Exposure of Xenopus embryos to alcohol
      during eye development produced marked gross ocular anomalies, including
      microphthalmia, incomplete closure of the choroid fissure, and malformation of
      the retina in 40% of the eyes examined. In parallel, alcohol (0.1%-0.5%) dose
      dependently and significantly reduced the expression of several eye marker genes,
      of which TBX5, VAX2, and Pax6 were the most vulnerable. Overexpression of
      catalase and of cytosolic and mitochondrial peroxiredoxin 5 restored the
      expression of these alcohol-sensitive eye markers and significantly decreased the
      frequency of ocular malformation from 39% to 21%, 19%, and 13% respectively. All
      these enzymes reduced alcohol-induced ROS production, but only peroxiredoxin 5
      inhibited RNS formation in the alcohol-treated embryos. CONCLUSIONS: The results
      suggest that oxidative and nitrosative stresses both contribute to alcohol
      induced fetal ocular injury.

PMID- 14691150
TI  - The benign concentric annular macular dystrophy locus maps to 6p12.3-q16.
AB  - PURPOSE: To describe the clinical findings and to identify the genetic locus in a
      Dutch family with autosomal dominant benign concentric annular macular dystrophy
      (BCAMD). METHODS: All family members underwent ophthalmic examination. Linkage
      analysis of candidate retinal dystrophy loci and a whole genome scan were
      performed. Five candidate genes from the linked locus were analyzed for mutations
      by direct sequencing. RESULTS: The BCAMD phenotype is initially characterized by
      parafoveal hypopigmentation and good visual acuity, but progresses to a retinitis
      pigmentosa-like phenotype. Linkage analysis established complete segregation of
      the BCAMD phenotype (maximum multipoint LOD score, 3.8) with DNA markers at
      chromosome 6, region p12.3-q16. Recombination events defined a critical interval
      spanning 30.7 cM at the long arm of chromosome 6 between markers D6S269 and
      D6S300. This interval encompasses several retinal dystrophy loci, including the
      ELOVL4 gene, mutated in autosomal dominant Stargardt disease, and the RIM1 gene,
      mutated in autosomal dominant cone-rod dystrophy, as well as the retinally
      expressed GABRR1 and -2 genes. Mutation screening of these four genes revealed no
      mutations. Sequence analysis of the interphotoreceptor matrix proteoglycan 1 gene
      IMPG1, also residing in the BCAMD locus, revealed a single base-pair change (T-
      >C) of nucleotide 1866 in exon 13, resulting in a Leu579Pro amino acid
      substitution. This mutation was absent in 190 control individuals. CONCLUSIONS:
      Significant linkage was found for the BCAMD defect with chromosomal 6, region
      p12.3-q16. A Leu579Pro mutation in the IMPG1 gene may play a causal role.

PMID- 14691151
TI  - Dominant, gain-of-function mutant produced by truncation of RPGR.
AB  - PURPOSE: The retinitis pigmentosa GTPase regulator (RPGR) is essential in the
      maintenance of photoreceptor viability. Mutations in the X-linked RPGR gene have
      generally been assumed to be recessive. This study was undertaken to investigate
      whether certain mutant RPGR alleles may act dominantly. METHODS: An RPGR
      transgene representing the RPGR ORF15 variant was placed under a non-tissue
      specific promoter and introduced into transgenic mice. The transgene was crossed
      into both a wild type (WT) and an RPGR null background. Its expression was
      analyzed by RT-PCR, immunoblot analysis, and immunofluorescence. Photoreceptor
      survival was assessed by electroretinography and histology. RESULTS: The RPGR
      transgene transcript underwent photoreceptor-specific, alternative splicing
      involving the purine-rich region of the ORF15 exon, generating a shortened mRNA
      and a premature stop codon. This truncation mutant caused more rapid
      photoreceptor degeneration than that in the RPGR null (knockout) mutant. The
      disease course was similar, whether the transgene was coexpressed with WT RPGR or
      expressed alone in the RPGR null background. CONCLUSIONS: Certain truncated forms
      of RPGR can behave as a dominant, gain-of-function mutant. These data suggest
      that human RPGR mutations are not necessarily null and some may also act as
      dominant alleles, leading to a more severe phenotype than a null mutant.

PMID- 14691152
TI  - Transgenic mice expressing Cre-recombinase specifically in M- or S-cone
      photoreceptors.
AB  - PURPOSE: To establish lines of transgenic mice that express Cre-recombinase in M-
      or S-cone photoreceptors for generating cone photoreceptor-specific (conditional)
      mutants. METHODS: Five kilobases of 5' upstream sequence of the mouse red-green
      (M) opsin gene or 0.5 kb of the mouse blue (S) opsin gene was cloned into a Cre
      expression plasmid. Transgenic mice were generated and characterized, and
      appropriate lines were established. The Cre-transgenic mice were crossed with
      ROSA26-lacZ mice (containing floxed beta-galactosidase gene) and analyzed to
      determine Cre-recombinase activity. RESULTS: Immunofluorescence study showed
      successful targeting of Cre-recombinase expression to cone photoreceptors. Double
      staining with anti-Cre antibody and anti-M- or anti-S-opsin antibody revealed
      specificity of Cre expression in M-opsin- and/or S-opsin-positive photoreceptors.
      Mating with ROSA26-lacZ mice demonstrated that Cre-recombinase was functionally
      active in M- or S-cones. CONCLUSIONS: Lines of transgenic mice that specifically
      express functional Cre-recombinase in M- or S-cones were established in this
      study. Because mutations in several widely expressed genes lead to photoreceptor
      degeneration, these transgenic mice should be valuable in generating conditional
      mutants to investigate the function of various genes specifically in cone
      photoreceptors.

PMID- 14691154
TI  - Heritability of risk factors for primary open-angle glaucoma: the Beaver Dam Eye
      Study.
AB  - PURPOSE: To investigate the family aggregation and heritability of risk
      indicators of primary open-angle glaucoma. METHODS: During the baseline
      examination of the Beaver Dam Eye Study, standardized measurements of intraocular
      pressure were performed with a Goldmann applanation tonometer. Stereoscopic
      photographs of the optic discs were taken of both eyes of each study participant.
      The eyes were graded for the size of the optic disc and cup according to a
      standardized protocol, with graders masked to other subject characteristics.
      Family members who had participated in the examination phase were identified.
      RESULTS: Correlations in sibling pairs (n = 1136), parent-child pairs (n = 514),
      and cousin pairs (n = 1807) for intraocular pressure were 0.17, 0.18, and 0.12,
      respectively and were all statistically significant, whereas the spouse pair
      correlation was not. Correlations for sibling, parent-child, and avuncular pairs
      were higher for vertical optic disc, vertical optic cup, and vertical cup-to-disc
      ratio than for intraocular pressure. Heritability estimates were 0.36, 0.55,
      0.57, and 0.48 for intraocular pressure, optic cup diameter, optic disc diameter,
      and cup-to-disc ratio, respectively. Correlations for the optic disc parameters
      were compatible with the amount of gene sharing in relative pairs of different
      degrees. CONCLUSIONS: Risk indicators of open-angle glaucoma correlate highly in
      families, and the patterns are consistent with the hypothesis of genetic
      determinants of these factors.

PMID- 14691153
TI  - Requirement of neuroD for photoreceptor formation in the chick retina.
AB  - PURPOSE: The genetic control of photoreceptor cell fate in the vertebrate retina
      is poorly understood. Published studies suggest that the genetic program
      underlying photoreceptor production involves neuroD, a proneural basic helix-loop
      helix (bHLH) gene. The present study investigates whether neuroD is necessary for
      photoreceptor cell development, by using loss-of-function analyses. METHOD:
      Engrailed-mediated active repression, antisense oligonucleotides, and small
      interfering RNA (siRNA) were used to attenuate neuroD expression and function in
      embryonic chick retina. The development of the retina was subsequently analyzed
      to determine whether these experimental manipulations would yield photoreceptor
      deficits in otherwise normal retina. RESULTS: Chick embryos infected with
      retroviruses expressing an active repression construct, En-NeuroDDeltaC,
      exhibited severe photoreceptor deficits. The outer nuclear layer (ONL) of the
      retina was no longer a contiguous structure, but became fragmented with regions
      that contained fewer or no photoreceptor cells. Photoreceptor deficiency was
      evident even before the retina became laminated, suggesting that active
      repression of NeuroD may have affected photoreceptor genesis. No deficiency was
      observed in other types of retinal cells. Culturing retinal cells in the presence
      of siRNA against neuroD resulted in a more than 50% reduction in the number of
      photoreceptor cells and an increase in the number of chx10+ cells. Subjecting the
      developing retina to antisense oligonucleotides against neuroD yielded fewer
      photoreceptor cells both in vivo and in vitro. Consistent with these
      observations, anti-NeuroD antibody specifically labeled the nuclei of the ONL.
      CONCLUSIONS: The data suggest a specific and an essential role of neuroD in
      photoreceptor formation in the chick retina.

PMID- 14691155
TI  - Diurnal axial length fluctuations in human eyes.
AB  - PURPOSE: This study sought diurnal variations of eye length in human subjects,
      analogous to those reported in laboratory animals. METHODS: Seventeen subjects,
      ages 7 to 53 (median 16) years and mean spherical equivalent refractive error 
      0.68 D (range, -3.00 to +1.00 D), underwent axial length measurements at multiple
      times during the day between 7 AM and 1 AM the following day, using partial
      coherence interferometry (PCI), a highly precise, noncontact method. Diurnal
      axial length measurements were obtained on two or more days in 10 of these
      subjects. RESULTS: During at least 1 day, 15 subjects showed a statistically
      significant (ANOVA, P < 0.05) diurnal fluctuation of axial length, with a
      magnitude generally between 15 and 40 microm. From the diurnal tracings that fit
      a sine curve using statistical criteria, the mean period of fluctuation was 21.6
      +/- 4.33 hours (SD), the mean amplitude was 27.1 +/- 11.9 microm (SD; range, 12.8
      41.4 microm), and the maximum axial length tended to occur at midday. Each of the
      subjects with multiple daily measurements showed axial length fluctuations on at
      least 1 day, but there were day-to-day differences in the diurnal variations:
      most notably, four subjects showed axial length fluctuations on each day; in
      others, the fluctuations were not observed on each testing day. CONCLUSIONS: The
      human eye undergoes diurnal fluctuations in axial length, with a pattern
      suggesting maximum axial length at midday. Based on repeated measurements, these
      daily fluctuations may not appear regularly in all subjects, suggesting the
      possibility of physiologic influences that must be defined.

PMID- 14691156
TI  - Impact of bilateral visual impairment on health-related quality of life: the Blue
      Mountains Eye Study.
AB  - PURPOSE: To assess the impact of visual impairment on health-related quality of
      life (HRQOL) in an older population and compare it with the impact of major
      medical conditions. METHODS: Participants of the second cross-sectional Blue
      Mountains Eye Study (BMES; n = 3509; mean age, 66.7 years; 57% female) were asked
      to complete the self-administered 36-item Short-Form health survey (SF-36), a
      comprehensive interview, and an eye examination. Visual impairment was defined as
      visual acuity less than 20/40 (better eye). RESULTS: Of 3154 (89.9%) participants
      with complete data, 172 (5.5%) had visual impairment due to refractive errors
      (correctable visual impairment) and 66 (2.1%) due to eye conditions
      (noncorrectable visual impairment; 49 mild, 9 moderate, 8 severe). After
      adjustment for demographic and medical confounders, there was a trend toward
      lower SF-36 scores in participants with noncorrectable impairment than in those
      with correctable impairment (physical component score [PCS] Ptrend = 0.01 and
      mental component score [MCS] Ptrend = 0.02). Increasingly severe noncorrectable
      visual impairment was associated with significantly poorer SF-36 scores in all
      but two dimensions. The impact of noncorrectable visual impairment was comparable
      to that from major medical conditions (e.g., stroke) and had a greater impact on
      mental than physical domains (mean MCS = 46.2, PCS = 41). No significant
      differences in HRQOL were demonstrated between visual impairment cases caused by
      age-related maculopathy and cataract, after adjusting for severity of visual
      impairment. CONCLUSIONS: Noncorrectable visual impairment was associated with
      reduced functional status and well-being, with a magnitude comparable to major
      medical conditions. These data have implications for disability weights such as
      those developed by the Global Burden of Disease study.

PMID- 14691157
TI  - Importance of vitreous liquefaction in age-related cataract.
AB  - PURPOSE: Vitrectomy is associated with the rapid progression of nuclear
      cataracts. This study was conducted to test the hypothesis that age-related
      liquefaction of the vitreous gel may also be associated with lens opacification.
      METHODS: Lenses from eye bank eyes were graded for nuclear, cortical, and
      posterior subcapsular opacities, and the amount of liquid vitreous was measured.
      RESULTS: Nuclear sclerosis (NS) grade, percent liquefaction, and age all
      correlated highly (P < 0.0001). After adjustment was made for age, the
      correlation between NS and percent liquefaction was 0.37 (P < 0.0001), and the
      correlation between age and NS after adjustment for liquefaction was 0.57 (P <
      0.0001). After the eyes were stratified into age groups, the correlation between
      NS and percent liquefaction was found to be highest in eyes from donors aged 51
      to 70. Cortical and posterior subcapsular opacities increased with age, but
      scores for these cataract types did not significantly correlate with vitreous
      liquefaction. CONCLUSIONS: Loss of vitreous gel during aging increases the risk
      of nuclear cataracts. Preservation or replacement of the vitreous gel may protect
      patients from nuclear cataract.

PMID- 14691158
TI  - Evaluation for safety of cultured corneal fibroblasts with cotreatment of alcohol
      and mitomycin C.
AB  - PURPOSE: To investigate the effects of alcohol and mitomycin C (MMC) on cultured
      corneal fibroblast of the rabbit to determine the safety of this compound for
      clinical use. METHOD: Corneal fibroblasts of New Zealand rabbits were cultured.
      Various concentrations (0%, 10%, 20%, 30%, 40%, and 60%) of ethanol were applied
      for 10, 20, 30, and 40 seconds to estimate dose- and time-dependent responses of
      cultured corneal fibroblasts. Cell viability was assessed using the MTT assay.
      Treated cells were additionally stained with Hoechst and annexin V for the
      identification of apoptosis. To investigate the coeffects of ethanol and MMC,
      dose and time dependency were evaluated after treatment with various
      concentrations of ethanol and MMC at different exposure times, and cell viability
      was established. To determine the latent effects of ethanol and MMC, cultured
      corneal fibroblasts were cotreated with various concentrations of ethanol and
      0.02% MMC for various periods and washed out, and then one group was incubated
      for 24 hours and another group was not incubated. Cell viability was estimated,
      and Hoechst and annexin V staining were performed before and after incubation. To
      establish the pathway of cell death, caspase-3 activities were measured in
      cultured corneal fibroblasts treated with ethanol or MMC. RESULTS: Cell viability
      after ethanol treatment was dose and time dependent. After application of ethanol
      for 10 seconds, cell viability was significantly reduced with 20% ethanol (P =
      0.001). At 20, 30, and 40 seconds of treatment with 10% ethanol, cell viability
      was significantly reduced (P < 0.01). Hoechst and annexin V staining revealed
      typical characteristics of apoptosis, such as bright fluorescent chromatin
      condensation, low fluorescence of nuclear fragmentation, and cell membrane
      shrinkage. Cell viability was more significantly reduced after cotreatment with
      alcohol and MMC, compared with treatment with alcohol alone. Moreover, cell
      viability was considerably decreased in the incubated group, compared with the
      nonincubated group. After 24 hours of incubation, cultured corneal fibroblasts
      cotreated with 10% ethanol and 0.02% MMC were stained with Hoechst and annexin V.
      Results were similar to data obtained with ethanol-treated cells. However, after
      application of 20% alcohol and MMC, a significant number of cells were not viable
      and were detached from the well walls. Caspase-3 activity significantly increased
      after treatment with 30% ethanol only and 30% ethanol in conjunction with 0.02%
      MMC. CONCLUSIONS: Alcohol and MMC reduced cell viability in cultured corneal
      fibroblasts in a dose- and time-dependent manner and had synergistic effects.
      This is related to the caspase-3 pathway, especially with concentrations of
      ethanol over 30%. Cotreatment with these reagents may significantly damage
      cultured corneal fibroblasts.

PMID- 14691159
TI  - Sterilized, freeze-dried amniotic membrane: a useful substrate for ocular surface
      reconstruction.
AB  - PURPOSE: To examine the feasibility of using sterilized, freeze-dried amniotic
      membrane (FD-AM) as a substrate for cultivating autologous corneal epithelial
      cells for ocular surface reconstruction. METHODS: Human AM deprived of amniotic
      epithelial cells by incubation with EDTA was freeze dried, vacuum packed, and
      sterilized with gamma-irradiation. The resultant FD-AM was characterized for its
      physical, biological, and morphologic properties by stretch stress tests,
      immunohistochemistry, electron microscopy, and cell culture. In addition, 3 weeks
      after an ocular surface injury, the conjunctivalized corneal surfaces of eyes in
      eight rabbits were surgically reconstructed by transplantation of autologous
      cultivated corneal epithelial cells on FD-AM. RESULTS: A stretch stress test
      revealed no significant differences between sterilized FD-AM and cryopreserved
      AM. Immunohistochemistry for several extracellular matrix molecules and electron
      microscopic analysis of FD-AM revealed that the process of drying and irradiation
      did not affect its biological and morphologic properties. The corneal epithelial
      cells cultivated on FD-AM had four to five stratified, well-differentiated cell
      layers. Corneas that were grafted with the cultivated corneal epithelial cells on
      FD-AM were clear and were all epithelialized at 10 days after surgery.
      CONCLUSIONS: The sterilized, freeze-dried AM retained most of the physical,
      biological, and morphologic characteristics of cryopreserved AM; consequently, it
      is a useful biomaterial for ocular surface reconstruction.

PMID- 14691160
TI  - Role of p38 MAP kinase in regulation of cell migration and proliferation in
      healing corneal epithelium.
AB  - PURPOSE: The purpose of the present study was to examine the roles of signaling
      pathways potentially activated by TGFbeta (i.e., Smad and p38 mitogen-activated
      kinase [MAPK]) in regulation of cell migration and proliferation of healing mouse
      corneal epithelium. METHODS: Activation of Smads or p38MAPK was evaluated by
      immunohistochemistry in healing mouse corneal epithelium after debridement. The
      role of endogenous TGFbeta or p38MAPK in epithelial healing was determined in
      organ-cultured mouse corneas with an epithelial defect, in the presence or
      absence of a TGFbeta-neutralizing antibody or p38MAPK inhibitors, respectively.
      Cell proliferation was evaluated by incorporation of bromodeoxyuridine. RESULTS:
      Migrating mouse corneal epithelium had minimal cell proliferation. Smad3 and -4
      were found in nuclei of normal corneal epithelium, whereas they were absent in
      nuclei of migrating cells in association with Smad7 upregulation on epithelial
      debridement. Administration of TGFbeta-neutralizing antibody reduced the protein
      expression of Smad7 in vivo after a corneal injury. In contrast, phosphorylation
      and nuclear translocation of p38MAPK were markedly evident in migrating
      epithelium during healing, but not in uninjured epithelium. In organ culture,
      addition of p38MAPK inhibitors blocked cell migration more markedly than
      neutralizing TGFbeta-antibody and enhanced cell proliferation in the injured
      corneal epithelium, in association with phosphorylation of Erk. CONCLUSIONS:
      Endogenous TGFbeta enhances migration of corneal epithelium during wound healing
      in mice. The p38MAPK, but not the Smad, cascade plays a major role in promoting
      cell migration and in suppressing cell proliferation in migrating epithelium.

PMID- 14691161
TI  - Proliferative effects of heparin-binding epidermal growth factor-like growth
      factor on pterygium epithelial cells and fibroblasts.
AB  - PURPOSE: To investigate the growth promoting and chemotactic effects of heparin
      binding epidermal growth factor-like growth factor (HB-EGF), recently shown to be
      upregulated by ultraviolet irradiation in pterygium-derived epithelium cells
      (PECs) and pterygium fibroblasts (PFs). METHODS: PECs and PFs were incubated with
      various concentrations of HB-EGF. Cell proliferation was evaluated by measurement
      of [3H]thymidine incorporation. The potential chemotactic effect of HB-EGF on
      these two cell lines was assessed with migration assays, using modified Boyden
      chambers and checkerboard analysis. RESULTS: Incubation of PECs and PFs with HB
      EGF resulted in a significant increase in [3H]thymidine incorporation compared
      with that of control cells. HB-EGF stimulated chemotaxis of both PECs and PFs.
      Maximum stimulation occurred at 1 ng/mL for PFs and 10 ng/mL for PECs. These
      effects were abolished by the addition of a neutralizing antibody to HB-EGF.
      CONCLUSIONS: The findings demonstrate the potential proliferative and chemotactic
      effects of HB-EGF on both PECs and PFs. This is the first study to illustrate the
      positive effect of a specific growth or chemotactic factor on the cellular
      elements of a pterygium.

PMID- 14691163
TI  - Eye position specificity of saccadic adaptation.
AB  - PURPOSE: The accuracy of saccadic eye movements is maintained throughout life by
      adaptive mechanisms. With the double-step target paradigm, eight human subjects
      were investigated to determine whether saccadic adaptation depends only on the
      eye-displacement vector, or also on eye position as a context cue when two
      saccades of identical vector are adapted simultaneously. METHODS: First,
      bidirectional adaptations (BDAs) of horizontal saccades of the same vector were
      induced in a single training phase. Each direction of adaptation in BDAs
      (backward and forward) was linked to one vertical eye position (e.g., forward
      adaptation performed with the eyes directed 12.5 degrees upward and backward
      adaptation with the eyes 25 degrees downward) and alternated from trial to trial.
      Second, unidirectional adaptations (UDAs) were tested in two control conditions
      in which training trials of a single direction (backward or forward) were
      presented at both 12.5 degrees and -25 degrees eye elevations. RESULTS: Opposite
      changes in saccade amplitude could develop simultaneously in BDA, indicating that
      saccadic adaptation depends on orbital eye position. Comparing these data with
      the control conditions further indicated that eye position specificity was
      complete for backward, but not for forward, adaptation. CONCLUSIONS: The results
      indicate that saccadic adaptation mechanisms use vectorial eye displacement
      signals, but can also take eye position signals into account as a contextual cue
      when the training involves conflicting saccade amplitude changes.

PMID- 14691162
TI  - Differential regulation of membrane-associated mucins in the human ocular surface
      epithelium.
AB  - PURPOSE: Membrane-associated mucins present in the apical cells of the ocular
      surface epithelium (MUC1, -4, and -16) are believed to contribute to the
      maintenance of a hydrated and wet-surfaced epithelial phenotype. Serum and
      retinoic acid (RA) have been used to treat drying ocular surface diseases. The
      goal of this study was to determine whether serum or RA regulates the production
      of membrane-associated mucins in human conjunctival epithelial cells. METHODS: A
      telomerase-immortalized human conjunctival epithelial cell line (HCjE) was used.
      Cells were cultured in serum-free medium to confluence and then cultured with
      either 10% calf serum or with 100 nM RA for 0 to 72 hours. Conventional RT-PCR
      was used to determine the expression of retinoic acid receptors (RARs) and
      quantitative real-time PCR was used to investigate the mRNA expression of MUC1, 
      4, and -16. Protein levels were assayed by immunoblot analysis, using the
      antibodies HMFG-2, 1G8, or OC125, which are specific to MUC1, -4 and -16,
      respectively. To determine whether RA-associated MUC4 mRNA induction is a direct
      or indirect effect, HCjE cells were treated with RA and the protein synthesis
      inhibitor cycloheximide (1.0 microg/mL) for 12 hours. RESULTS: MUC1 and -16, but
      not -4, mRNAs were detectable in HCjE cells grown in serum-free medium. Real-time
      PCR revealed that MUC4 mRNA was significantly induced by serum 3 hours after its
      addition, and that MUC1 and MUC16 mRNA levels were significantly upregulated at
      72 hours. Western blot analysis demonstrated that the MUC1, -4, and -16 proteins
      increased over time after addition of serum. Conventional RT-PCR analysis
      demonstrated that RAR-alpha and -gamma mRNA were expressed in native human
      conjunctival tissue as well as in the HCjE cells. Treatment with RA upregulated
      the expression of both MUC4 and -16 mRNA and protein, but MUC1 was unaffected.
      Because the protein synthesis inhibitor cycloheximide did not prevent the RA
      associated induction of MUC4 mRNA, the action of RA on the MUC4 promoter may be
      direct. CONCLUSIONS: The membrane-associated mucins of the ocular surface
      epithelia, MUC1, -4, and -16, are differentially regulated by serum and RA in the
      telomerase-immortalized human conjunctival epithelial cell line. Serum derived
      from vessels in the conjunctiva may play an important role in mucin regulation in
      the ocular surface epithelia. These data also support the clinical efficacy of
      autologous serum and RA application in patients with ocular surface diseases.
      Furthermore, the data suggest that MUC4 and -16 are particularly important
      hydrophilic molecules involved in maintenance of a healthy ocular surface.

PMID- 14691164
TI  - Influence of orientation of exiting wire of search coil annulus on torsion after
      saccades.
AB  - PURPOSE: Research has shown that the orientation of the exiting wire from a
      scleral search coil (nasal in the original coil, inferior in the modified coil)
      influences the pattern of torsion associated with blinks, presumably due to the
      upper eyelid touching the wire. The present study was conducted to investigate
      whether coil wire orientation also influences the pattern of torsion during
      fixation after saccades and consequently influences parameters that determine
      Listing's plane and Donders' law. METHODS: Three-axis, binocular eye rotations
      were recorded in three healthy human subjects looking at an array of small light
      emitting diodes at a 124-cm distance. They made predominantly vertical or
      predominantly horizontal saccades (5-40 degrees, amplitude) at three (0 +/- 20
      degrees) azimuths, or elevations. RESULTS: With the modified coil, the horizontal
      component of Listing's primary position was similar for horizontal (mean temporal
      deviation, 2.9 degrees) and vertical (3.3 degrees) saccades. With the original
      coil, the horizontal component of primary position was more temporal after
      horizontal (12.3 degrees) than vertical (6.1 degrees) saccades. The vertical
      component of primary position was similar with both coils after horizontal and
      vertical saccades. Listing's plane was thinner with the modified coil after
      horizontal (standard deviation of torsion from a plane of 0.71 degrees vs. 1.31
      degrees) and vertical (0.84 degrees vs.1.67 degrees) saccades. The standard
      deviation of torsion at a given eye position (Donders' law) was smaller with the
      modified coil. CONCLUSIONS: Measures of torsion after horizontal or vertical
      saccades depend on whether the coil wire exits nasally or inferiorly and, with
      the original coil, whether the saccades are horizontal or vertical. Lid contact
      may account for these potential artifacts. They must be appreciated in the
      interpretation of three-dimensional search coil recordings, using the scleral
      annulus.

PMID- 14691165
TI  - Myosin light chain 1 isoforms in slow fibers from global and orbital layers of
      canine rectus muscles.
AB  - PURPOSE: Initial results of an examination of the low molecular mass (< or =45
      kDa) protein composition of canine rectus muscle homogenates, based on gel
      electrophoresis, revealed a distinct difference between the global and orbital
      layers in the myosin light chain (MLC)-1 region. The objectives of the present
      study were, therefore, to identify isoforms of MLC1 in homogenates of the global
      and orbital layers of adult canine rectus muscles and to determine the MLC1
      isoform expression pattern among single muscle fibers isolated from both layers.
      METHODS: Muscle homogenates and single fibers from the global and orbital layers
      of canine rectus muscles were analyzed, using sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). Matrix-assisted laser
      desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) was used to
      identify a protein band in the orbital layer that comigrated with MLC1 in the
      adult canine atrium. RESULTS: Adult canine extraocular rectus muscles expressed
      embryonic skeletal/atrial MLC1 (MLC1(E/A)), in addition to the fast-type MLC1
      (MLC1F) and slow-type MLC1 (MLC1S) isoforms expressed in limb skeletal muscles.
      MLC1(E/A) was detected in slow fibers of the orbital but not the global layer,
      and MLC1S was detected in slow fibers in only the global but not the orbital
      layer. Densitometric analysis of gel bands from homogenates supported these
      results, with significantly greater amounts of MLC1S in the global layer and of
      MLC1(E/A) in the orbital layer. CONCLUSIONS: MLC1(E/A) is expressed in rectus
      muscles of adult dogs. Furthermore, two types of slow fibers, distinguished on
      the basis of MLC1 isoform expression, exist in separate layers of canine rectus
      muscles.

PMID- 14691166
TI  - Model of endothelin-1-induced chronic optic neuropathy in rat.
AB  - PURPOSE: To describe a model of chronic endothelin (ET)-1 administration to the
      optic nerve and evaluate its effect on retinal ganglion cell (RGC) and axon
      survival in rat. METHODS: Osmotic minipumps were surgically implanted in one eye
      of 113 Brown Norway rats to deliver 0.05, 0.10, 0.20, or 0.40 microg ET-1 per day
      (3.3, 6.7, 13.4, and 26.8 microM, respectively), or balanced salt solution (BSS)
      to the immediate retrobulbar optic nerve; the fellow untreated eye served as the
      control. Before pump implantation, RGCs were retrogradely labeled with
      fluorochrome. Animals were killed at 21, 42, or 84 days. RGC survival was
      expressed as the ratio of RGC counts in experimental versus control eyes in
      wholemounted retinas, whereas axon survival was expressed similarly from electron
      micrographs of the optic nerves. Serial optic disc changes were evaluated using
      scanning laser tomography. The effect of ET-1 (3 microL topical application of
      10(-5) M) on blood flow in the surgically exposed optic nerve was measured using
      laser Doppler flowmetry in a separate group of five animals. RESULTS: ET-1 led to
      a mean reduction in optic nerve blood flow of 68%. There were no significant
      differences in RGC survival among the four ET-1 doses used in this study. Pooled
      across all ET-1 doses, RGC survival decreased incrementally at 21, 42, and 84
      days (P < 0.001; mean +/- SD, 0.77 +/- 0.25, 0.60 +/- 0.27, and 0.50 +/- 0.26,
      respectively) and was statistically significantly lower at each time point than
      in the BSS-treated animals. The axon survival data also showed a similar time
      dependent loss. Only one of 21 animals showed significantly increased disc
      cupping, and there was no relationship between RGC survival and change in
      cupping. CONCLUSIONS. Chronic administration of ET-1 to the rat optic nerve
      results in a time-dependent loss of RGCs and their axons without apparent change
      in optic disc topography.

PMID- 14691167
TI  - Effects of TGF-beta2 in perfused human eyes.
AB  - PURPOSE: TGF-beta2 is known to be present at elevated levels in the aqueous humor
      of patients with primary open-angle glaucoma (POAG). Studies have shown that TGF
      beta2 influences cultured trabecular meshwork (TM) cells, but the effects of this
      cytokine on intact TM and outflow facility have not been studied. The purpose of
      this study was to investigate whether TGF-beta2 treatment induces changes in
      outflow facility and morphologic changes in the TM tissue and whether these
      changes are comparable to those previously recorded in glaucomatous eyes.
      METHODS: Baseline facility was measured in paired human eyes (n = 8 pairs), with
      a constant-flow anterior segment culture system. Medium perfusing experimental
      eyes was then supplemented with activated human recombinant TGF-beta2 (3.0 ng/mL,
      comparable to or slightly greater than measured aqueous humor levels in patients
      with POAG), and facility was measured for at least 8 days. At the conclusion of
      the perfusion, eyes were fixed and processed for light microscopy, transmission
      electron microscopy, and immunolabeling studies. RESULTS: TGF-beta2 perfusion
      reduced outflow facility by 27% (P = 0.03) and promoted focal accumulation of
      fine fibrillar extracellular material in multilayered structures under the inner
      wall of Schlemm's canal. In treated eyes, Schlemm's canal was 27% shorter (P =
      0.02), and the length of the inner wall apparently available for fluid flow was
      33% less (P = 0.001), both compared with paired control eyes. CONCLUSIONS: TGF
      beta2 reduces outflow facility when perfused into cultured human anterior
      segments. Furthermore, TGF-beta2 affects the extracellular matrix of the
      trabecular meshwork in a manner that is consistent with the observed reduction in
      outflow facility. Although the distribution of accumulated fibrillar material was
      different in these perfused eyes than that in POAG, the difference could be due
      to variation in biomechanical environment for TM cells in cultured anterior
      segments compared with the living eye. Overall, these results support the
      hypothesis that elevated TGF-beta2 levels in the aqueous humor play a role in the
      pathogenesis of the ocular hypertension in POAG.

PMID- 14691168
TI  - Inhibition of endotoxin-induced uveitis and potentiation of cyclooxygenase-2
      protein expression by alpha-melanocyte-stimulating hormone.
AB  - PURPOSE: The efficacy of alpha-melanocyte-stimulating hormone (alpha-MSH) on
      endotoxin-induced uveitis (EIU) was investigated in rats. Several studies have
      demonstrated that there are various inflammatory reactions mediated by an alpha
      MSH receptor in macrophages. In addition, as it is known that cyclooxygenase
      (COX)-2 is induced by a variety of stimuli and plays an important role in
      inflammation, COX-2 expression was also investigated in macrophage cells treated
      with alpha-MSH in vitro to clarify its anti-inflammatory effect. METHODS: EIU was
      induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS).
      The number of infiltrating cells and protein concentration in the aqueous humor
      collected 24 hours after the LPS treatment was determined. The levels of
      prostaglandin (PG)-E2, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and
      monocyte chemoattractant protein (MCP)-1 production were determined. RAW 264.7
      cells were pretreated with various concentrations of alpha-MSH for 24 hours and
      subsequently incubated with 10 microg/mL LPS for 24 hours. COX-2 protein
      expression was analyzed by Western blot analysis. RESULTS: alpha-MSH suppressed
      the development of EIU in a dose-dependent fashion. The treatment with alpha-MSH
      reduced the PGE2, TNF-alpha, IL-6, and MCP-1 concentrations in aqueous humor. The
      COX-2 protein expression in the alpha-MSH group decreased. CONCLUSIONS: This
      study suggests that alpha-MSH has an antiocular inflammatory effect, by
      suppression of PGE2, TNF-alpha, IL-6, and MCP-1 production and blocking of COX-2
      expression.

PMID- 14691169
TI  - Acanthamoeba keratitis: the role of domestic tap water contamination in the
      United Kingdom.
AB  - PURPOSE: The incidence of acanthamoeba keratitis (AK) in the UK is some 15 times
      that in the United States and seven times that in Holland. To investigate reasons
      for this higher frequency, a study of the role of domestic tap water as a
      potential source of AK was undertaken. METHODS: Tap outlets from the homes of 27
      patients with culture-proven AK were sampled and cultured for free-living amoebae
      (FLA). For all Acanthamoeba isolates, mitochondrial DNA (mtDNA) restriction
      fragment length polymorphisms (RFLPs) and cytochrome oxidase (cox 1/2) sequence
      typing was performed to determine the similarity between corneal and tap water
      isolates. RESULTS: FLA, including Acanthamoeba, were isolated from 24 (89%) of 27
      homes, and the presence within the homes varied significantly with tap water
      temperature and location: 19 (76%) of 25 bathroom sink cold taps sampled compared
      with 6 (24%) of 25 hot and 9 (47%) of 19 kitchen cold taps compared with 3 (16%)
      of 19 of hot kitchen taps. Acanthamoeba were isolated from 8 (30%) of 27 homes
      (five bathroom sink cold taps, one cloakroom cold tap, one bath, and one bedroom
      sink mixer [hot/cold] taps). In six cases, identical Acanthamoeba mtDNA profiles
      were found for the clinical and home tap water isolates. In keeping with UK
      plumbing practice, 24 of 27 homes had internal roof water storage tanks to supply
      domestic taps, but the mains fed the kitchen cold tap. CONCLUSIONS: Water storage
      tanks promote colonization of domestic water with FLA, including Acanthamoeba,
      and hence increase the risk of AK. This accounts for the significantly greater
      incidence of AK in the UK and supports advice to avoid using tap water in contact
      lens care routines.

PMID- 14691170
TI  - Anti-TNFalpha therapy modulates the phenotype of peripheral blood CD4+ T cells in
      patients with posterior segment intraocular inflammation.
AB  - PURPOSE: Posterior segment intraocular inflammation (PSII) is a putative Th1 CD4+
      cell mediated autoimmune disorder. In experimental autoimmune uveoretinitis,
      neutralization of tumor necrosis factor (TNF)-alpha induces suppression of Th1
      cells, macrophage activation, and target organ damage. Previous studies
      implicated an efficacy of anti-TNFalpha therapies in patients with PSII. This
      study investigated the immunomodulatory effect of anti-TNFalpha therapy to find
      predictors of effective immunosuppression in PSII. METHODS: Fifteen patients with
      PSII refractory to conventional immunosuppressive therapy received a single
      infusion of a recombinant protein generated by fusing the p55 TNFalpha receptor
      with human IgG1. During 17 treatment periods, visual acuity (logarithm of the
      minimum angle of resolution [logMAR]) was monitored as a response criterion.
      Phenotype markers of CD4+ T cells were analyzed before and 2, 4, and 12 weeks
      after therapy. Expression of intracellular cytokines (interferon [IFN]-gamma,
      interleukin [IL]-10, and TNFalpha) and Th1/Th2-specific chemokine receptors
      (CXCR3, CCR4, and CCR5) on peripheral blood CD4+ T cells was determined using
      flow cytometry. RESULTS: The fraction of IL-10-expressing CD4+ T cells was
      increased during 12 of 17 treatment periods within 2 weeks after treatment.
      During eight treatment periods, this increase was associated with an improvement
      of visual acuity of at least 0.2 logMAR within 4 weeks (P = 0.029). The ratio
      between IL-10- and IFNgamma-expressing CD4+ T cells was significantly increased 2
      weeks after therapy (P = 0.015). There was no significant change of CXCR3, CCR4,
      or CCR5 expression. CONCLUSIONS: Neutralizing TNFalpha activity in PSII increases
      the fraction of peripheral blood CD4+ T cells expressing IL-10, which correlates
      with a recovery of visual function.

PMID- 14691171
TI  - Vulnerability of allogeneic retinal pigment epithelium to immune T-cell-mediated
      damage in vivo and in vitro.
AB  - PURPOSE: Because retinal pigment epithelium (RPE) constitutively expresses class
      I major histocompatibility complex (MHC) molecules, and CD95 ligand and secretes
      immunosuppressive factors, the vulnerability of these cells to attack by immune T
      cells is open to question. This study was conducted to determine the
      vulnerability of allogeneic RPE to damage by specifically sensitized T cells,
      both in vivo within the subretinal space, and in vitro. METHOD: BALB/c
      lymphocytes presensitized to C57BL/6 antigens were injected into the subretinal
      space of eyes of C57BL/6 and gld/gld mice, and the eyes were examined clinically
      and histologically. RPE eyecups were produced from mouse eyes by removing the
      anterior segment and neuronal retina, leaving an intact monolayer of RPE.
      Sensitized BALB/c lymphocytes were placed in the RPE eyecup and incubated for 4
      hours. The RPE layer of the eyecups was assessed by confocal microscopy for
      viability, after staining with propidium iodide and acridine orange. RESULT: Eyes
      that received T cells sensitized to C57BL/6 antigens displayed a circumscribed
      patch of persistent choroidal "whitening" clinically and a disrupted RPE cell
      layer histologically at the injection site at 5 days after injection. By 14 days,
      only RPE cells at the injection site were lost. RPE in eyecup preparations was
      relatively resistant in vitro to cytolysis by sensitized T cells, whether the
      eyecups were obtained from CD95-deficient or wild-type mice. CONCLUSIONS: RPE
      monolayers, both in vivo and in vitro, are relatively resistant to immune
      mediated attack by specifically sensitized T cells. This relative lack of
      vulnerability is independent of the expression of CD95 ligand by target RPE cells
      and implies that immune barriers to acceptance of allogeneic RPE transplants may
      be less than if transplanted cells are from nonocular tissues.

PMID- 14691172
TI  - Chemokines in autoimmune lacrimal gland disease in MRL/MpJ mice.
AB  - PURPOSE: MRL/MpJ-fas+/fas+ (MRL/+) and MRL/MpJ-fas(lpr)/fas(lpr) (MRL/lpr) mice
      undergo spontaneous development of inflammation of the lacrimal and salivary
      glands, similar to that in the human disorder Sjogren's syndrome. Previous work
      has shown that these lesions appear to be largely T helper (Th)-2-driven, as
      evidenced by the substantially greater expression of IL-4 than interferon-gamma.
      The relative contributions of selected chemokines associated with Th1 and Th2
      immune responses were assessed. METHODS: Lacrimal glands from MRL/+ and MRL/lpr
      mice, at ages 1.5 through 9 months were evaluated by immunohistochemistry for the
      chemokines monocyte chemoattractant protein (MCP)-1 (also known as chemokine
      ligand [CCL]-2), MCP-5 (CCL12), thymus activation regulated chemokine (TARC; or
      CCL17), and macrophage-derived chemokine (MDC; or CCL22). Additional lacrimal
      glands were tested by real-time RT-PCR for chemokines MCP-1 and -5, which are
      associated with Th2 and Th1 responses, respectively. RESULTS: By
      immunohistochemistry a significantly greater proportion of mononuclear
      inflammatory cells in the lacrimal gland lesions stained for MCP-1 (29%-48%
      depending on age) compared with MCP-5 (1%-3% depending on age) both in MRL/+
      (mean difference 34.2%, P < 0.001) and MRL/lpr (mean difference 33.6%, P < 0.001)
      substrains. Real-time RT-PCR studies showed higher transcript levels of MCP-1
      compared with MCP-5, in both MRL/+ (median difference, 37.3; P < 0.0001) and
      MRL/lpr (median difference, 77.1; P < 0.0001) mice. Relative transcripts of MCP-1
      increased with age in both MRL/+ mice (P = 0.02) and MRL/lpr mice (P = 0.03).
      Staining for TARC was present on lacrimal gland ductular cells but not on the
      infiltrating lymphocytes, and staining for MDC was present on scattered
      individual cells throughout the lacrimal gland, but not on infiltrating
      lymphocytes. CONCLUSIONS: The predominant expression of a Th2-associated
      chemokine in the lacrimal gland lesions in this murine model of Sjogren's
      syndrome may contribute to the predominantly Th2-type lymphoid infiltrate in
      these tissues.

PMID- 14691173
TI  - Gap junction processing and redistribution revealed by quantitative optical
      measurements of connexin46 epitopes in the lens.
AB  - PURPOSE: To map changes in the structure and function of fiber cell gap junctions
      that occur with lens differentiation. METHODS: Equatorial lens sections were
      fluorescently labeled with antibodies to the gap junction protein connexin
      (Cx)46, the membrane marker wheat germ agglutinin, and the nuclear stain
      propidium iodide. Two-photon microscopy and digital image analysis were used to
      quantify label and cell morphology as a function of radial distance (r/a) across
      the lens. Loop- and tail-specific Cx46 antibodies were used to identify regions
      of posttranslational modification. Local fiber cell coupling was imaged in situ
      using two-photon flash photolysis of caged fluorescein. RESULTS: Antibody
      labeling showed that the cytoplasmic tail of Cx46 was removed in two zones (r/a
      approximately 0.9 and r/a approximately 0.7). In addition, with increasing depth,
      the large radially aligned plaques of peripheral fiber cells became fragmented
      and dispersed around the cell membrane, and cells became more circular in cross
      section. Fluorescein transfer between peripheral fiber cells was highly
      anisotropic and occurred predominantly within a column of fiber cells, resulting
      in radially directed transport. In regions beyond the zone of nuclear loss,
      transport was more isotropic and occurred across columns of fiber cells.
      CONCLUSIONS: The cleavage of Cx46 is associated with a spatial redistribution of
      gap junction plaques. The distribution of gap junction plaques around the cell
      membrane can explain the observed directionality of intercellular solute
      transfer. The findings suggest that the processing and redistribution of gap
      junction proteins is central to controlling radial and circumferential solute
      gradients in different regions within the lens.

PMID- 14691174
TI  - Spatial characteristics of receptor-induced calcium signaling in human lens
      capsular bags.
AB  - PURPOSE: Despite recent improvements in intraocular lens (IOL) design, posterior
      capsule opacification (PCO) arising from lens cell growth remains a major
      problem. Calcium signaling has been shown to play a major role in driving human
      lens cell growth, and therefore it is necessary to understand the underlying
      mechanisms. METHODS: Calcium signaling was studied in capsular bags (ex vivo)
      removed from donors who had undergone earlier cataract surgery. Fresh capsular
      bags were also produced from intact donor lenses and cultured in serum-free EMEM
      for up to 8 weeks. Both preparations were loaded with Fura-2, and ratiometric
      imaging of cytoplasmic calcium was performed using epifluorescence techniques.
      Changes were monitored in response to 10 microM ATP (adenosine triphosphate), 10
      microM acetylcholine, and 10 ng/mL epidermal growth factor (EGF), and data were
      collected from equatorial, posterior, and anterior regions. Calcium transients
      were also recorded from anterior epithelial specimens in response to pilocarpine.
      RESULTS: All equatorial cells of ex vivo bags responded to ATP and EGF, but not
      to acetylcholine, and this pattern was maintained in the cultured bags. Posterior
      capsule cells of both preparations also had similar properties, in which a large
      proportion of the cells responded to ATP and EGF, but not to acetylcholine.
      Conversely, most anterior cells of the in vivo bags responded to pilocarpine,
      whereas no cells in the cultured bags responded. All cells in the fresh anterior
      epithelium responded to pilocarpine. CONCLUSIONS: Ex vivo capsular bags retain
      the region-specific calcium-signaling characteristics of the native lens. Apart
      from losing M1 muscarinic expression properties, the in vitro capsular bags also
      reflect region-specific signaling properties and therefore provide a good model
      for the investigation of the contribution of calcium-signaling to PCO.

PMID- 14691175
TI  - Effect of deamidation of asparagine 146 on functional and structural properties
      of human lens alphaB-crystallin.
AB  - PURPOSE: To elucidate the effect of deamidation on the structural and functional
      properties of human alphaB-crystallin. METHODS: Site-directed mutagenesis was
      used to generate three deamidated mutants of alphaB-crystallin: N78D, N146D, and
      N78D/N146D. The mutations were confirmed by DNA sequencing and matrix-assisted
      desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Recombinant
      native alphaB-crystallin (wild type [WT]) and the three mutated alphaB species
      were expressed, and each species was purified to homogeneity by ion-exchange
      chromatography followed by hydrophobic interaction chromatography. The structural
      and functional properties compared with WT protein were investigated,
      respectively, by static light scattering (SLS), circular dichroism (CD), and
      fluorescence spectroscopy and by determining chaperone activity with the use of
      three substrates. RESULTS: Native WT and the N78D mutant showed relatively higher
      chaperone activity compared with the N146D and N78D/N146D mutants with all the
      substrates. Further, during binding experiments with 1-anilino-8
      naphthalenesulfonate (ANS), the WT and N78D mutant showed relatively more solvent
      exposed hydrophobic residues than the N146D and N78D/N146D mutants. On
      determining far-UV circular dichroism and tryptophan (Trp) fluorescence spectra,
      significant secondary and tertiary structural changes were observed in the N146D
      and N78D/N146D mutants compared with WT and the N78D mutant. The static light
      scattering data showed a high order of oligomerization in all the three mutants.
      N146D and N78D/N146D formed the largest oligomers of 750 and 770 kDa,
      respectively, compared with WT (580 kDa). CONCLUSIONS: The results show that the
      deamidation of N146 but not of N78 have profound effects on the structural and
      functional properties of alphaB-crystallin.

PMID- 14691176
TI  - The effects of phenylephrine on pupil diameter and accommodation in rhesus
      monkeys.
AB  - PURPOSE: Phenylephrine is used to dilate the iris through alpha-adrenergic
      stimulation of the iris dilator muscle. Sympathetic stimulation of the ciliary
      muscle is believed to be inhibitory, decreasing accommodative amplitude.
      Investigations in humans have suggested some loss of functional accommodation
      after phenylephrine. It is unclear whether this loss is due to direct action of
      phenylephrine on the ciliary muscle or to secondary optical factors associated
      with mydriasis. The purpose of this study was to determine whether phenylephrine
      affects Edinger-Westphal (EW)-stimulated accommodation in rhesus monkeys.
      METHODS: The time course for maximum mydriasis was determined by videographic
      pupillography after phenylephrine instillation in 10 normal rhesus monkeys.
      Static and dynamic EW-stimulated accommodative responses were studied in five
      iridectomized rhesus monkeys before and after phenylephrine instillation.
      Accommodative amplitude was measured with a Hartinger coincidence refractometer.
      Dynamic accommodative responses were measured with infrared photorefraction, and
      functions were fitted to the data to determine peak velocity versus accommodative
      response relationships. RESULTS: The maximum dilated pupil diameter of 8.39 +/-
      0.23 mm occurred 15 minutes after administration of phenylephrine. In
      iridectomized monkeys, postphenylephrine accommodative amplitudes were similar to
      prephenylephrine amplitudes. Dynamic analysis of the accommodative responses
      showed linear peak velocity versus accommodative amplitude relationships that
      were not statistically different before and after phenylephrine. CONCLUSIONS:
      alpha-Adrenergic stimulation causes a strong pupil dilation in noniridectomized
      monkey eyes but does not affect EW-stimulated accommodative amplitude or dynamics
      in anesthetized, iridectomized rhesus monkeys.

PMID- 14691177
TI  - Interferon-gamma induces apoptosis of lens alphaTN4-1 cells and proteasome
      inhibition has an antiapoptotic effect.
AB  - PURPOSE: Targeted ectopic expression of interferon-gamma (IFN-gamma) in the eyes
      of transgenic mice disrupts lens differentiation, upregulates immunoproteasomes,
      and causes cataract. In this study, the hypothesis that IFN-gamma induces
      proteasome-dependent apoptosis of lens epithelial cells was tested. METHOD:
      Murine lens epithelial alphaTN4-1 cells were treated with IFN-gamma. Apoptosis
      was measured using annexin V-FITC and propidium iodide (PI) staining, and DNA
      fragmentation. IFN-gamma-inducible mRNA and protein expressions were measured by
      RT-PCR and Western blot analysis. Caspase activities were measured using
      colorimetric substrates and poly (ADP ribose) polymerase (PARP) cleavage. The
      effect of proteasome inhibition was tested with MG132 and lactacystin. RESULTS:
      IFN-gamma treatment at a concentration that induces immunoproteasome expression
      causes an approximately 20% increase in early apoptotic cells as observed by
      annexin V-FITC/PI staining and the increase in DNA fragmentation. IFN-gamma
      induced apoptosis was accompanied by upregulation of apoptosis-related genes,
      including a dramatic increase in signal transducer and activator of transcription
      (STAT)-1 and interferon consensus sequence binding protein (ICSBP), a more than 2
      fold increase in IRF-1, and a 1.7- to 2-fold increase in caspase-1 mRNA. Bcl-2
      mRNA decreased 2.4- to 3.0-fold, whereas Bax mRNA was unchanged. The Bax-to-Bcl-2
      protein ratio increased by 1.6-fold. Caspase-1 and -8 activities were higher, but
      there was no increase in caspase-3 activity. Proteasome inhibitors MG132 and
      lactacystin protected the cells against IFN-gamma-induced apoptosis. A positive
      control treatment with staurosporine (STP) caused increased caspase-3 activity,
      which was inhibited by MG132. CONCLUSIONS: IFN-gamma causes apoptosis of alphaTN4
      1 cells, accompanied by upregulation of known effectors. IFN-gamma-induced
      apoptosis involves Bcl-2 family proteins and caspases. Proteasome inhibition has
      antiapoptotic effects on IFN-gamma-induced apoptosis. It also inhibits the STP
      induced increase in caspase-3 activity. If IFN-gamma-induced apoptosis of lens
      epithelial cells contributes to cataractogenesis, the proteasome may be a
      therapeutic target.

PMID- 14691178
TI  - Thioltranferase mediated ascorbate recycling in human lens epithelial cells.
AB  - PURPOSE: This study was undertaken to investigate whether thioltransferase
      (TTase) exhibits dehydroascorbate (DHA) reductase activity in human lens
      epithelial cells. METHODS: TTase was investigated for DHA reductase activity in
      vitro by the method of glutathione reductase-coupled spectrophotometric assay.
      DHA reductase activities of human lens epithelial (HLE-B3) cell lysate and TTase
      depleted HLE-B3 cell lysate were determined with a 6-deoxy-6-fluoro-DHA probe and
      19F-nuclear magnetic resonance (NMR) spectroscopy. TTase-overexpressing and 
      depleted HLE-B3 cells were investigated for DHA reductase activity. RESULTS:
      TTase showed DHA reductase activity at a Km of 0.15 mM and Vmax of 35 nmol/min.
      Investigation of the DHA reductase activity in human lens epithelial (HLE-B3)
      cell lysate, by using a 6-deoxy-6-fluoro-DHA probe and 19F-NMR spectroscopy,
      revealed that cell lysate possesses significant DHA reductase activity. This
      activity decreased extensively when TTase was depleted from the cell lysate by
      immunoprecipitation. In a cell-free system with externally added DHA, nearly 70%
      of the recycling ability was diminished when TTase was removed from the lysate.
      The TTase-overexpressing cells increased DHA reductase activity twofold. HLE-B3
      cells showed an ability to take up and recycle DHA, and this ability was
      increased approximately twofold in the TTase-transfected cells. Suppression of
      TTase in HLE-B3 cells by an antisense cDNA strategy resulted in a 77% decrease in
      DHA reductase activity. CONCLUSIONS: The data provide evidence that TTase plays a
      major role in ascorbic acid recycling in human lens epithelial cells.

PMID- 14691179
TI  - Feasibility of drug delivery to the posterior pole of the rabbit eye with an
      episcleral implant.
AB  - PURPOSE: To evaluate the feasibility of a nonbiodegradable polymeric episcleral
      implant as a new controlled intraocular delivery system of betamethasone (BM) to
      the posterior pole of the eye. METHODS: The episcleral implant, which is composed
      of a drug-releasing component and a suture tag, released BM through an ethylene
      vinyl acetate membrane. The implants were placed on the sclera in 12 eyes of 12
      Japanese white rabbits so that the drug-releasing surface could attach to the
      sclera at the posterior pole. BM concentrations in the aqueous humor, vitreous,
      and retina-choroid (posterior half and anterior half) were determined by high
      performance liquid chromatography (HPLC) at weeks 1, 2, and 4 after implantation.
      In addition, the intraocular tissue distribution of the drug was evaluated by
      fluorescein microscopy after implantation of the implant loaded with 6-carboxy
      fluorescein diacetate (6-CFDA) as a drug marker. Retinal toxicity was evaluated
      by electroretinography and histologic examination. RESULTS: The implant showed
      zero-order release profiles both in vitro and in vivo for 4 weeks. BM
      concentrations in the retina-choroid after implantation were maintained above the
      concentrations effective for suppressing inflammatory reactions for at least 4
      weeks. The BM concentration was greater in the posterior half of the retina
      choroid than in the vitreous. It was confirmed that 6-CFDA penetrated through the
      sclera and dispersed into the retina-choroid. Fluorescence from 6-CFDA gradually
      decreased in intensity with increased distance from the implantation site.
      Electroretinography and histologic study showed no substantial toxic reactions.
      CONCLUSIONS: These findings suggest that the episcleral implant may be a useful
      drug carrier for intraocular delivery of BM, especially for the posterior part of
      the eye.

PMID- 14691180
TI  - Purification, molecular cloning, and expression of a novel growth-promoting
      factor for retinal pigment epithelial cells, REF-1/TFPI-2.
AB  - PURPOSE: Retinal pigment epithelial (RPE) cells are known to play important roles
      in maintaining the homeostasis of the retina and in controlling choroidal
      neovascularization. The purpose of this study was to identify a factor or factors
      that would stimulate RPE cells to proliferate. METHODS: To isolate such a factor,
      100 L of human-fibroblast-conditioned medium underwent ion-exchange, hydrophobic,
      and reverse-phase chromatographies followed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The growth-promoting activity of the factor
      was examined in a human K-1034 RPE cell line and human primary RPE cells.
      RESULTS: The different chromatographic processes isolated a 31-kDa factor that
      had RPE cell growth-promoting properties. This factor, which we have named RPE
      cell factor (REF)-1, promotes growth of RPE cells but not of human umbilical vein
      endothelial cells (HUVECs). The amino-terminal sequence and molecular cloned cDNA
      of REF-1 were identical with those of tissue-factor pathway inhibitor (TFPI)-2, a
      family of TFPIs, and placental protein (PP)-5, a serine protease inhibitor. The
      cDNA expression of REF-1/TFPI-2 with pcDL-pSRalpha vector in Chinese hamster
      ovary (CHO) cells confirmed the growth-promoting activity for RPE cells. The
      major component of the recombinant REF-1/TFPI-2 expressed in CHO cells had a
      molecular mass of 31 kDa and exerted growth-promoting activity in RPE cells but
      not in human endothelial cells and fibroblasts in vitro. REF-1/TFPI-2 also had
      protease inhibitory activity. The other family factor, TFPI-1, did not promote
      RPE cell growth. CONCLUSIONS: REF-1/TFPI-2 is a novel growth-promoting factor for
      RPE cells but not for endothelial cells and fibroblasts. Its properties make it
      potentially beneficial for intraocular therapy for the repair and maintenance of
      RPE cells.

PMID- 14691181
TI  - Myogenic tone and reactivity of the rat ophthalmic artery.
AB  - PURPOSE: To study and quantify myogenic behavior and reactivity of the rat
      ophthalmic artery to pressure and different vasoactive substances in vitro.
      METHODS: Rat ophthalmic arteries (diameter of 217 +/- 6 microm, n = 22) were
      isolated, cannulated with glass pipettes in an arteriograph and pressurized in a
      physiological buffer. Internal diameter was continuously monitored. The effect of
      intraluminal pressure on the diameter was assessed and concentration-response
      curves to different constrictor and dilator agonists were obtained at an
      intraluminal pressure of 70 mm Hg. RESULTS: Myogenic tone developed at an
      intraluminal pressure of 30 to 40 mm Hg, continued to increase, and was
      maintained up to a pressure of 199 mm Hg in these arteries. Arteries dilated and
      constricted in response to 16 and 60 mM potassium, respectively. Endothelin-1 was
      the most potent and efficacious constrictor, with a biphasic concentration
      response curve, followed by vasopressin, serotonin, U-46619 and phenylephrine.
      Carbachol was the most efficacious dilator, followed by isoprenaline. The peptide
      dilators calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide
      (VIP) were potent but less efficacious than carbachol and isoprenaline. Histamine
      and adenosine were even less potent and less efficacious dilators. NG-nitro-L
      arginine methyl ester (L-NAME) constricted and indomethacin dilated the arteries.
      CONCLUSIONS: This study provides the first direct evidence for myogenic
      autoregulatory properties and pharmacological heterogeneity in the rat ophthalmic
      artery.

PMID- 14691182
TI  - Basal laminar deposit formation in APO B100 transgenic mice: complex interactions
      between dietary fat, blue light, and vitamin E.
AB  - PURPOSE: Dietary fat intake has been proposed as a mechanism of sub-RPE deposit
      formation. It has been demonstrated recently that sub-RPE deposits develop in 16-
      to 18-month-old C57BL/6 mice fed a high-fat diet and exposed to blue-green light.
      Hyperlipidemia also develops in these mice after they consume a high-fat diet.
      Because hyperlipidemia also develops in young C57BL/6 mice that overexpress APO
      B100, the major apolipoprotein in LDL cholesterol, this research was conducted to
      determine whether high-fat diet and plasma hyperlipidemia correlate with
      formation of basal laminar deposits (BLD) in young transgenic mice. METHODS: APO
      B100 and wild-type C57BL/6 2-month-old mice were fed a high-fat diet for 4.5
      months. After the first month, the right eyes were exposed to seven 5-second
      doses of nonphototoxic levels of blue-green light (20 mJ of argon 488 nm) over 2
      weeks. Three months later, transmission electron microscopy (TEM) of the retina
      was performed to evaluate whether sub-RPE deposits correlate with plasma
      cholesterol and triglyceride levels. Several eyes were stained with filipin to
      detect cholesterol and osmium-thiocarbohydrazide-osmium (OTO) to detect neutral
      lipids in Bruch's membrane (BrM). A third group of APO B100 2-month-old mice were
      pretreated with vitamin E subcutaneously twice a week throughout the experiment
      and underwent the same light-exposure protocol. RESULTS: Mice fed a high-fat diet
      had a more elevated plasma triglyceride and cholesterol level than those that
      consumed a regular diet. Young APO B100 mice fed a high-fat diet had blood lipid
      levels higher than those in young wild-type mice that consumed high-fat diets,
      and these two groups had higher lipid levels than animals with regular diets, as
      shown previously in wild-type C57BL/6 (old and young). Eyes of APO B100 mice
      treated with blue-green light showed a high frequency of "moderate BLD", whereas
      the nonexposed eyes did not. In contrast, no BLD formed in either eye of the wild
      type young mice fed a high-fat diet. In individual affected mice, only a weak
      correlation was observed between deposit severity and plasma lipid concentration.
      None of the eyes in mice with sustained hyperlipidemia with or without BLD
      demonstrated obvious widespread neutral lipid or cholesterol deposition in BLD or
      BrM. However, vitamin E-treated mice showed minimal formation of BLD.
      CONCLUSIONS: Although a high-fat diet is a necessary precondition for this model
      of BLD, the findings demonstrated a convincing direct correlation between plasma
      lipidemia and deposit severity. The results suggest that age, as shown in
      previous studies, and high-fat predispose to formation of BLD by altering hepatic
      and/or RPE lipid metabolism in ways more complicated than plasma hyperlipidemia
      alone.

PMID- 14691183
TI  - Transplantation of Schwann cell line clones secreting GDNF or BDNF into the
      retinas of dystrophic Royal College of Surgeons rats.
AB  - PURPOSE: To assess the capacity of a retrovirus-engineered Schwann cell line
      (SCTM41), transfected with either a glial cell line-derived neurotrophic factor
      (GDNF) construct or a brain-derived neurotrophic factor (BDNF) construct, to
      sustain visual function in the dystrophic Royal College of Surgeons (RCS) rat.
      METHODS: Cell suspensions were injected into the subretinal space of the right
      eye of 3-week-old dystrophic RCS rats through a transscleral approach. The left
      eye remained as an unoperated control. Sham-surgery animals received injections
      of carrier medium plus DNase to the right eye. All animals were placed on oral
      cyclosporine. At 8, 12, 16, and 20 weeks of age, animals were placed in a head
      tracking apparatus and screened for their ability to track square-wave gratings
      at various spatial frequencies (0.125, 0.25, and 0.5 cyc/deg). At the end of the
      experiment, the animals were perfused and processed for histologic assessment of
      photoreceptor survival. RESULTS: Animals with SCTM41-GDNF-secreting cells, on
      average, head tracked longer than animals with SCTM41-BDNF-secreting cells, and
      both performed better than those injected with the parent SCTM41 line. All
      tracked longer than sham-surgery or nonsurgical dystrophic eyes. Each cell type
      demonstrated preservation of photoreceptors up to at least 4 months of age, over
      and above the sham-surgery control. CONCLUSIONS: Engineered Schwann cells sustain
      retinal structure and function in the dystrophic RCS rat. Cells overexpressing
      GDNF or BDNF had a greater effect on photoreceptor survival than the parent line
      or sham surgery. This study demonstrates that ex vivo gene therapy and subsequent
      cell transplantation can be effective in preserving photoreceptors from the cell
      death that normally accompanies retinal degeneration.

PMID- 14691184
TI  - Rod and cone photoreceptor function in patients with cone dystrophy.
AB  - PURPOSE: To determine the extent of rod and cone photoreceptor dysfunction in
      patients with cone dystrophy using psychophysical and electrophysiological tests.
      METHODS: Ten patients with cone dystrophy participated. Rod and cone system
      psychophysical thresholds were measured as a function of retinal eccentricity.
      Bright-flash full-field electroretinograms were obtained under dark-adapted (rod
      mediated) and light-adapted (cone-mediated) conditions. The a-wave data were
      fitted with a model based on photopigment transduction to obtain values for log
      Rmax (maximum response) and log S (sensitivity). b-Wave parameters were also
      examined by fitting a nonlinear, saturating function (the Naka-Rushton equation)
      to the rod-mediated responses. Oscillatory potentials were measured to the cone
      mediated high-intensity flashes. RESULTS: On average, the rod-mediated
      psychophysical thresholds were elevated by 0.5 log unit. These threshold
      elevations did not differ significantly with retinal eccentricity. In contrast,
      cone-mediated psychophysical thresholds were elevated up to 3.0 log units.
      Threshold elevation was greatest in the central retinal locations. For rod
      mediated conditions, the a-wave Rmax parameter was significantly reduced in three
      patients; the a-wave log S parameter was within normal limits. The rod-mediated b
      wave Rmax parameter was reduced in six patients; log k was abnormal in one
      patient. For cone-mediated conditions, the a-wave Rmax parameter was reduced in
      six patients and the a-wave log S parameter was reduced in two patients. The cone
      system oscillatory potentials were abnormal in nine patients. CONCLUSIONS:
      Patients with cone dystrophy show different patterns of psychophysical rod versus
      cone system sensitivity losses with retinal eccentricity. The full-field
      electrophysiological data indicate that most of the patients had abnormal cone
      photoreceptor function. Some patients also showed rod photoreceptor
      abnormalities. The rod system changes were smaller than the cone system changes.

PMID- 14691185
TI  - Histological findings in experimental macular surgery with indocyanine green.
AB  - PURPOSE: To analyze the effect of different concentrations and application
      intervals of indocyanine green (ICG) on the retina in an experimental setting of
      macular surgery. METHODS: Twenty-one porcine eyes were used within 5 hours after
      enucleation. The eyes were hemisected and the vitreous removed. Different doses
      of ICG (up to 1 mg) were applied over the trephined macula, and the remainder of
      the eyecup was filled with a balanced salt solution (BSS). Both the ICG solution
      and the BSS were drained after 30 or 60 seconds and the complete eyecup irrigated
      and filled with fresh BSS. The posterior pole was then illuminated with a
      standard surgical light pipe and light source at maximum power for 3 minutes.
      Both the ICG-treated retina and the nontreated surrounding retina were processed
      for histology. RESULTS: Exposure of the retina at different concentrations of ICG
      either for 30 or 60 seconds, followed by illumination, caused no histologically
      detectable damage compared with the controls. No microarchitectural
      disorganization or cellular disruption was detected. The vitreoretinal interface
      seemed unaffected. CONCLUSIONS: Previously described severe damage to the inner
      retina of human donor eyes could not be found with even higher doses of ICG in
      this porcine model. Although differences within the species may contribute to
      these contradictory results, it is conceivable that the postmortem time and the
      vitality of the tissue influence the outcome in this ex vivo system.

PMID- 14691186
TI  - Oncofetal fibronectin in diabetic retinopathy.
AB  - PURPOSE: Imbalance between extracellular matrix protein synthesis and degradation
      is a key feature of diabetic retinopathy. Fibronectin, a predominant constituent
      of the extracellular matrix, has been shown to undergo alternative splicing to
      produce embryonic isoforms in various pathologic conditions, such as fibrotic
      diseases and tumorigenesis. Two such isoforms, oncofetal fibronectin variants
      that are characterized by the inclusion of the oncofetal domains A and B, were
      the focus of the present study. METHODS: The expression of oncofetal fibronectin
      variants was determined in human vitreous samples obtained from patients
      undergoing vitrectomy for proliferative diabetic retinopathy and nondiabetes
      associated ocular conditions such as macular hole. In addition, an animal model
      of chronic diabetes and cultured endothelial cells was used to elucidate the
      mechanistic basis for this aberrant expression of oncofetal fibronectin. RESULTS:
      Expression of fibronectin containing the oncofetal domain B was upregulated in
      the vitreous of patients with diabetic retinopathy. CONCLUSIONS: Use of a well
      established animal model of chronic diabetic complications and cultured
      endothelial cells showed that diabetes-induced upregulation of oncofetal
      fibronectin is, in part, dependent on hyperglycemia-induced transforming growth
      factor-beta1 and endothelin-1. Furthermore, the data suggest that oncofetal
      fibronectin is involved in endothelial cell proliferation.

PMID- 14691187
TI  - Retinal function in normal and diabetic eyes mapped with the slow flash
      multifocal electroretinogram.
AB  - PURPOSE: It has been suggested that late components of the standard multifocal
      electroretinogram (mfERG) are preferentially affected by diabetes mellitus. The
      slow-flash (sf-)mfERG stimulates with flashes separated by dark periods,
      facilitating interpretation of late first-order response components compared with
      standard multifocal stimulation. Retinal function and response component changes
      were examined using the sf-mfERG in diabetic subjects with and without diabetic
      retinopathy. METHODS: Eighteen control subjects, 12 diabetic patients without
      retinopathy and 17 diabetic patients with nonproliferative diabetic retinopathy
      (NPDR), were tested monocularly. A total of 103 areas of the central 45 degrees
      were stimulated by pseudorandom 100-cd/m2 flashes separated by at least 53.3 ms.
      Major components and the amplitude of the first-order sf-mfERGs were examined.
      Each subject's N1, P1, and N2 implicit times (ITs) and scalar product amplitudes
      (SPs) were measured at all 103 retinal locations and converted into z-scores
      based on the control values. Abnormalities were defined as z-scores greater than
      2.33 (P < 0.01). RESULTS: Local functional abnormalities were found in both the
      diabetic patients with NPDR and in those without retinal disease. In both groups
      of diabetic patients, most abnormalities occurred more frequently in the inferior
      retina. Later components (P1 and N2) of the local sf-mfERGs were not
      preferentially affected by diabetes. The local SP and P1 IT measures
      distinguished the subject groups better than N1 IT and N2 IT. CONCLUSIONS: Local
      functional retinal abnormalities in diabetic persons with or without NPDR can be
      detected and mapped by the sf-mfERG. Diabetes and NPDR do not, however,
      preferentially affect the late P1 and N2 response components.

PMID- 14691188
TI  - Contrast-processing deficits in melanoma-associated retinopathy.
AB  - PURPOSE: To evaluate the hypothesis that patients with melanoma-associated
      retinopathy (MAR) have a selective functional loss within the magnocellular (MC)
      pathway of the cone system, with sparing of parvocellular (PC) pathway function.
      METHODS: Two patients with MAR, ages 57 and 61 years, with normal Snellen visual
      acuity, participated in the study. Contrast sensitivity was measured at spatial
      frequencies ranging from 0.25 to 8 cycles per degree (cpd), using two paradigms
      (steady pedestal and pulsed pedestal) designed to assess the functional integrity
      of the MC and PC pathways, respectively. Results in patients with MAR were
      compared with those in 10 visually normal observers, aged 23 to 57 years.
      RESULTS: Both patients with MAR showed a loss of contrast sensitivity compared to
      normal observers, but the pattern of loss differed for the two testing paradigms.
      For the steady-pedestal paradigm (presumed MC-pathway mediation), the patients'
      sensitivity loss was greatest at the lowest spatial frequency (0.25 cpd) and the
      sensitivity loss decreased systematically with increasing spatial frequency. For
      the pulsed-pedestal paradigm (presumed PC-pathway mediation), the sensitivity
      loss was greatest at an intermediate spatial frequency of 1 cpd. For both
      paradigms, the patients' sensitivities were within the normal range at the
      highest spatial frequency (8 cpd), consistent with their normal visual acuity.
      CONCLUSIONS: The contrast sensitivity deficits of patients with MAR under
      photopic conditions are not specific to the MC pathway, as proposed previously,
      but instead are related to the spatial frequency of the test target. The overall
      pattern of contrast sensitivity loss shown by the patients with MAR is consistent
      with the dysfunction at the level of the retinal bipolar cells that is presumed
      to underlie the MAR syndrome.

PMID- 14691189
TI  - Nicotine increases size and severity of experimental choroidal
      neovascularization.
AB  - PURPOSE: Cigarette smoking is the strongest environmental risk factor for all
      forms of age-related macular degeneration (AMD). In the present study, the
      influence of nicotine on the severity of choroidal neovascularization (CNV) in a
      mouse model of neovascular AMD and its effects on vascular smooth muscle cells
      derived from mouse choroid were investigated. METHODS: A mouse model for CNV was
      used to study the effects of nicotine in young and middle-aged mice. Nicotine was
      administered orally in the drinking water to achieve serum levels consistent with
      those of chronic smokers. Hexamethonium, a nonspecific nicotinic receptor
      antagonist, was injected subconjunctivally to counteract the effects of nicotine.
      A mouse choroidal vascular smooth muscle cell line was exposed to nicotine,
      vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF),
      or a combination of one of the factors and nicotine. Cell growth was determined
      by cell counts, and the activity of matrix metalloproteinase (MMP)-2 and -9 was
      quantified by gel zymography. RESULTS: Nicotine administration resulted in
      increased size and vascularity of CNV, and older mice developed a greater
      relative increase than younger mice. This effect was blocked by subconjunctival
      hexamethonium. Choroidal vascular smooth muscle cells demonstrated a
      statistically significant increase in growth after exposure to a combination of
      PDGF and nicotine. Nicotine also reversed VEGF-induced suppression of MMP-2
      activity. CONCLUSIONS: Nicotine increases size and severity of experimental CNV
      in the present mouse model, possibly by potentiating PDGF-mediated upregulation
      of proliferation of choroidal smooth muscle cells or by other mechanisms. These
      results suggest that non-neuronal nicotinic receptor activation probably mediates
      some of the harmful effects of cigarette smoking in wet AMD.

PMID- 14691190
TI  - Delayed regeneration of foveal cone photopigments in Vogt-Koyanagi-Harada disease
      at the convalescent stage.
AB  - PURPOSE: To evaluate the physiological characteristics of the macula in patients
      with Vogt-Koyanagi-Harada disease during the convalescent stage with specific
      reference to the kinetics of foveal cone photopigment regeneration. METHODS: Six
      eyes of three patients at the convalescent stage of Vogt-Koyanagi-Harada disease
      were studied. All the eyes had best corrected visual acuity of 1.0 or better and
      had had no recurrence of inflammation for at least 12 months after the last
      episode. Foveal cone densitometry (FCD), focal macular electroretinograms, color
      vision tests, two-color perimetry, and optical coherence tomography (OCT) were
      performed. RESULTS: No regeneration of cone photopigments was detected within the
      7-minute testing time by FCD in all eyes at the first examination after the last
      episode. However, the other functional tests were normal, and the OCT-determined
      macular morphology was also normal. The regeneration kinetics of the foveal cone
      photopigment improved in three of six eyes at 36, 37, and 19 months after the
      last episode, whereas the other three remained delayed at 18, 18, and 49 months.
      CONCLUSIONS: These findings suggest that a disorder of the foveal cone
      photopigment regeneration, and its recovery, requires a significantly longer time
      than that of other macular functions in some patients with Vogt-Koyanagi-Harada
      disease.

PMID- 14691191
TI  - Hepatocyte growth factor and its role in the pathogenesis of retinal detachment.
AB  - PURPOSE: Hepatocyte growth factor (HGF) regulates barrier function of retinal
      pigment epithelial (RPE) cells. The purpose of this study was to determine
      whether overexpression of HGF in the RPE induces retinal detachment (RD).
      METHODS: E1/E3-deleted adenoviral vectors encoding HGF (Ad CMV.HGF), green
      fluorescent protein (Ad CMV.GFP), or connective tissue growth factor (AdCMV.CTGF)
      were injected subretinally in adult pigmented rabbits (5 x 10(4) plaque-forming
      units [pfu]/eye). Animals were observed for up to 28 days with fundus
      photography. HGF expression in the retina and vitreous was determined using
      immunohistochemistry, and ELISA. Histopathologic examinations were performed with
      light and electron microscopy. RESULTS: Control eyes injected with AdCMV.GFP
      showed GFP expression almost exclusively in the RPE monolayer. Eyes injected with
      AdCMV.HGF showed strong HGF immunopositivity in RPE cells at the injection site.
      Elevated HGF levels were found in the vitreous peaking at postinjection day 7,
      diminishing to baseline by postinjection day 28. Eyes injected with AdCMV.HGF
      developed chronic RD and chronic inflammation in the choroid within the time
      frame of HGF expression. Groups of proliferating RPE cells were seen in the
      subretinal space in the region of the RD, and in some cases multilayered cellular
      membranes developed. No RD and minimal morphologic changes were seen in the eyes
      injected with AdCMV.GFP or AdCMV.CTGF. CONCLUSIONS: Overexpression of HGF in RPE
      induces chronic, serous RD with subretinal proliferation of RPE. This work
      provides insight into the pathogenesis of RD and suggests that HGF should be
      further investigated as a target for therapeutic intervention in RD.

PMID- 14691192
TI  - Ischemia-induced changes of AMPA-type glutamate receptor subunit expression
      pattern in the rat retina: a real-time quantitative PCR study.
AB  - PURPOSE: To investigate whether the previously observed decrease in
      immunoreactivity of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA)-type glutamate receptor subunits GluR1, -2, -3, and -4 after ischemia
      reperfusion in the rat retina is associated with changes at the mRNA expression
      level. Furthermore, to study possible changes in the ratios of alternative splice
      variants of GluR2 and -4 and possible changes in the subunit composition of the
      receptor complex after ischemia-reperfusion. The ischemia-induced changes were
      related to expression levels of immediate early genes, c-fos and c-jun, and to
      expression levels of different cell-type-specific transcripts. METHODS: A 60
      minute ischemic event was induced unilaterally in the rat eye by cannulating the
      anterior chamber and raising the intraocular pressure. Reperfusion was allowed to
      occur for 2 hours up to 28 days. Total RNA was isolated from the retinas and
      transcript levels were assessed by real-time quantitative PCR (qPCR). RESULTS: A
      differential decrease was observed in the expression levels of all AMPA-type GluR
      subunits 2 hours after ischemia-reperfusion, with a significant downregulation of
      GluR2 and -3 transcript levels. At the long-term (72 hours-4 weeks), expression
      levels for all four subunits were decreased by approximately 64%. No changes were
      observed, either in the expression ratio of GluR2 and -4 splice variants, or in
      the relative expression of the different subunits. Immediate early genes c-fos
      and c-jun were transiently upregulated. Expression levels of the ganglion-cell
      specific transcripts Thy-1 and neurofilament and of the AII-amacrine-specific
      transcript parvalbumin decreased after ischemia-reperfusion, whereas the ON
      bipolar cell transcripts mGluR6 and PKCalpha did not show ischemia-induced
      changes. CONCLUSIONS: Shortly after ischemia-reperfusion immunolabeling of GluR1,
      -2/3, and -4 is strongly decreased, whereas the corresponding mRNA levels are not
      affected, indicating degradation at the protein level. In contrast, the GluR2
      mRNA level is reduced, whereas immunostaining is not yet affected, suggesting
      that the GluR2 protein is relatively stable under postischemia conditions. The
      long-term decrease in mRNA levels of all AMPA-type GluR subunits suggests that
      ischemia affects a main component of the excitatory retinal neurotransmission. It
      remains to be investigated whether these changes contribute to the subsequent
      neurodegeneration.

PMID- 14691193
TI  - The effect of attention on conventional automated perimetry and luminance size
      threshold perimetry.
AB  - PURPOSE: To investigate the effects of divided attention on conventional
      automated perimetry (CAP) and luminance size threshold perimetry (LSTP). METHODS:
      Ten healthy subjects, ages 27 to 65, with two perimetry types (CAP and LSTP) were
      tested in random order. At a later session, these tests were given with a mental
      workload to simulate the effect of anxiety or distraction on subjects performing
      visual field testing, also in random order. The mental workload, the Paced
      Auditory Serial Addition Test (PASAT), was first administered to each subject,
      and the score was recorded. During the visual field testing, the PASAT was again
      administered continuously. Each subject was instructed to attend primarily to the
      PASAT while taking each visual field test. RESULTS: CAP was affected by the
      addition of the PASAT, with a worsening of sensitivity from an average of 30.0 +/
      0.67 to 24.2 +/- 7.4 dB with a range of -0.04 to -23.2 dB (P = 0.04). LSTP
      showed a generalized reduction in threshold 1.71 +/- 0.22 to 2.35 +/- 0.72 dB
      with a range of 0.12 to -2.17 dB (P = 0.25). The percentage of correct responses
      on the PASAT was not significantly different between CAP (76.9%) and LSTP
      (74.8%). False-positive and -negative catch trial responses were increased during
      CAP with PASAT testing (P = 0.009). A substantial increase of fixation losses
      occurred during CAP with PASAT (3.7-16.2, P = 0.002). LSTP with PASAT showed
      increases in localization error (P < 0.001) and reaction time (P = 0.004).
      CONCLUSIONS: Divided attention significantly affects performance on conventional
      automated perimetry with its fixed size stimuli and when the stimuli are scaled
      (LSTP). The deficits may simulate nerve-fiber-bundle-like defects.

PMID- 14691194
TI  - Test-retest reliability of clinical Shack-Hartmann measurements.
AB  - PURPOSE: To evaluate the stability of clinical monochromatic aberrometry
      measurements over a wide range of time scales. METHODS: Monochromatic aberrations
      in four normal eyes were measured with a clinical Shack-Hartmann aberrometer. A
      chin rest or a supplemental bite bar attachment was used to stabilize head and
      eye position. Five repeated measurements were taken within one test (5 frames, t
      < 1 second) without realignment. With realignment between each measurement,
      aberration measurements were repeated five times (t < 1 hour) on each day, at the
      same time of day on five consecutive days, and again on 5 days at monthly
      intervals. A control experiment studied the effect of systematically misaligning
      the eye to determine whether fixation errors can account for the variation in the
      repeated measurements. RESULTS: Variability of wavefront root mean square (RMS)
      error (excluding defocus and astigmatism) was tracked across repeated
      measurements. Variances for different time scales were: 8.10 x 10(-5) microm2 (t
      < 1 second), 3.24 x 10(-4) microm2 (t < 1 hour), 4.41 x 10(-4) microm2 (t < 1
      week), 9.73 x 10(-4) microm2 (t < 1 year). Bite bar and chin rest data were
      almost identical. Rotational fixation error up to 3 degrees accounts for only
      part of the variability. CONCLUSIONS: Increased variability in aberration maps
      between days and months indicates biological fluctuations that are large enough
      to prevent achievement of "perfect vision," even in the unlikely event that
      spherical and astigmatic refractive errors are corrected perfectly. However, lack
      of stability does not justify withholding treatment. A lasting benefit of
      aberration correction is expected despite temporal variability.

PMID- 14691196
TI  - Association between physical activity and blood pressure is modified by variants
      in the G-protein coupled receptor 10.
AB  - Hypertension is strongly related to cardiovascular disease and all-cause
      mortality. Exercise reduces blood pressure but the response varies between
      individuals. The mechanisms by which physical activity energy expenditure (PAEE)
      modifies blood pressure are not fully defined but include modulation of
      sympathetic tone. Novel polymorphisms in the G-protein coupled receptor (GPR10)
      have been linked with high blood pressure. GPR10 may mediate the relationship
      between PAEE and blood pressure via central nervous mechanisms. We examined
      whether two GPR10 polymorphisms (G-62A and C914T) modify the association between
      PAEE and blood pressure in the MRC Ely study (N=687). When stratified by the
      C914T genotype, there were between-group differences for body mass index (BMI)
      (P=0.05), diastolic blood pressure (DBP) (P=0.006), and systolic blood pressure
      (SBP) (P=0.005). No differences were found between G-62A genotypes. The
      previously reported inverse relationship between PAEE and blood pressure was not
      observed in minor allele carriers for either polymorphism (A62 carriers: DBP beta
      1.11, P=0.52; SBP beta-1.66, P=0.52. T914 carriers: SBP beta=3.27; P=0.60) but
      was in common allele homozygotes (G62G: DBP beta-6.18 P=0.00001; SBP beta-8.54
      P=0.0001. C914C: SBP beta-7.07; P=0.00001). This corresponded to a significant
      interaction between PAEE and GPR10 polymorphisms on DBP (G-62A: P=0.006) and SBP
      (G-62A: P=0.008. C914T: P=0.068). Significant interactions were observed between
      haplotype (derived from G-62A and C914T), PAEE, and blood pressure (DBP: P=0.08;
      SBP: P=0.023). The effect of physical activity on blood pressure is highly
      variable at population level. Knowledge of GPR10 genotype may define those who
      are least likely to benefit from physical activity. These findings may have
      relevance in the targeted treatment of hypertensive disease.

PMID- 14691195
TI  - Ac-SDKP reverses inflammation and fibrosis in rats with heart failure after
      myocardial infarction.
AB  - Inflammation may play an important role in the pathogenesis of cardiac fibrosis
      in heart failure (HF) after myocardial infarction (MI). N-acetyl-seryl-aspartyl
      lysyl-proline (Ac-SDKP) is a naturally occurring antifibrotic peptide whose
      plasma concentration is increased 4- to 5-fold by angiotensin-converting enzyme
      inhibitors. We tested the hypothesis that in rats with HF after MI, Ac-SDKP acts
      as an anti-inflammatory cytokine, preventing and also reversing cardiac fibrosis
      in the noninfarcted area (reactive fibrosis), and thus affording functional
      improvement. We found that Ac-SDKP significantly decreased total collagen content
      in the prevention group from 23.7+/-0.9 to 15.0+/-0.7 microg/mg and in the
      reversal group from 22.6+/-2.2 to 14.4+/-1.6 (P<0.01). Interstitial collagen
      volume fraction and perivascular collagen were likewise significantly reduced. We
      also found that infiltrating macrophages were reduced from 264.7+/-8.1 to 170.2+/
      9.2/mm2, P<0.001 (prevention), and from 257.5+/-9.1 to 153.1+/-8.5 mm2, P<0.001
      (reversal), while transforming growth factor (TGF)-beta-positive cells were
      decreased from 195.6+/-8.4 to 129.6+/-5.7/mm2, P<0.01 (prevention), and from
      195.6+/-8.4 to 130.7+/-10.8/mm2, P<0.01 (reversal). Ac-SDKP did not alter either
      blood pressure or left ventricular hypertrophy (LVH); however, it depressed
      systolic cardiac function in the prevention study while having no significant
      effect in the reversal group. We concluded that Ac-SDKP has an anti-inflammatory
      effect in HF that may contribute to its antifibrotic effect; however, this
      decrease in fibrosis without changes in LVH was not accompanied by an improvement
      in cardiac function.

PMID- 14691197
TI  - Mediators of bradykinin-induced vasorelaxation in human coronary microarteries.
AB  - To investigate the mediators of bradykinin-induced vasorelaxation in human
      coronary microarteries (HCMAs), HCMAs (diameter approximately 300 microm)
      obtained from 42 heart valve donors (20 men and 22 women; age range, 3 to 65
      years; mean age, 46 years) were mounted in Mulvany myographs. In the presence of
      the cyclooxygenase inhibitor indomethacin, bradykinin relaxed preconstricted
      HCMAs in a concentration-dependent manner. N(G)-nitro-L-arginine methyl ester and
      ODQ (inhibitors of nitric oxide [NO] synthase and guanylyl cyclase, respectively)
      and the NO scavenger hydroxocobalamin, either alone or in combination, shifted
      the bradykinin concentration-response curve to the right. Removal of H2O2 (with
      catalase), inhibition of cytochrome P450 epoxygenase (with sulfaphenazole or
      clotrimazole) or gap junctions (with 18alpha-glycyrrhetinic acid or
      carbenoxolone), and blockade of large- (BK(Ca)) and small- (SK(Ca)) conductance
      Ca2+-dependent K+ channels (with iberiotoxin and apamin), either alone or in
      addition to hydroxocobalamin, did not affect bradykinin. In contrast, complete
      blockade of bradykinin-induced relaxation was obtained when we combined the
      nonselective BK(Ca) and intermediate-conductance (IK(Ca)) Ca2+-dependent K+
      channel blocker charybdotoxin and apamin with hydroxocobalamin. Charybdotoxin
      plus apamin alone were without effect. Inhibition of inwardly rectifying K+
      channels (K(IR)) and Na+/K+-ATPase (with BaCl2 and ouabain, respectively) shifted
      the bradykinin concentration-response curve 10-fold to the right but did not
      exert an additional effect in the presence of hydroxocobalamin. In conclusion,
      bradykinin-induced relaxation in HCMAs depends on (1) the activation of guanylyl
      cyclase, K(IR), and Na(+)/K(+)-ATPase by NO and (2) IK(Ca) and SK(Ca) channels.
      The latter are activated by a factor other than NO. This factor is not a
      cytochrome P450 epoxygenase product or H2O2, nor does it depend on gap junctions
      or BK(Ca) channels.

PMID- 14691198
TI  - Forced homodimerization by site-directed mutagenesis alters guanylyl cyclase
      activity of natriuretic peptide receptor B.
AB  - Natriuretic peptides mediate their physiologic effects through activation of
      membrane-bound, guanylyl cyclase-coupled receptors (NPRs). Receptor dimerization
      is an important feature of signal transduction. This study was aimed at
      characterizing structurally important residues of the extracellular ligand
      binding domain of NPR-B for receptor dimerization and cGMP generation. Deletion
      mutagenesis was used to replace cysteine residues at positions 53 (C53S), 417
      (C417S), and 426 (C426S) by serine. Receptor expression, dimerization, whole-cell
      cGMP response, and guanylyl cyclase activity of membrane fractions were
      determined in stably transfected COS-7 cells. C53S, C417S, and C426S mutants were
      expressed and found to form disulfide-bridged covalent dimers. In contrast to NPR
      B and C53S, C417S and C426S mutants displayed constitutive activity in whole
      cells (C417S, 146+/-12%, P<0.01; C426S, 153+/-7% of ligand-independent NPR-B cGMP
      generation, P<0.01). The cGMP response of C417S and C426S mutants in whole cells
      was dose dependent and approximately 4 times lower than that in NPR-B, whereas it
      was blunted in C53S-transfected cells (1 micromol/L CNP, NPR-B 2868+/-436%; C53S,
      206+/-16% of control, P<0.001 vs NPR-B, C417S, and C426S). Guanylyl cyclase assay
      in transfected cells confirmed the constitutive activity of C417S and C426S
      mutants. These data suggest that receptor dimerization by covalent disulfide
      bridges alters ligand-independent as well as ligand-dependent receptor activity.
      Localization of the crosslink in relation to the cell membrane is important for
      configuration of the extracellular domain and the consecutive signal
      transduction.

PMID- 14691199
TI  - Apamin-sensitive K+ currents mediate arachidonic acid-induced relaxations of
      rabbit aorta.
AB  - Arachidonic acid induces an endothelium-dependent relaxation of the rabbit aorta
      that is blocked by lipoxygenase inhibitors. The cellular vasodilatory mechanisms
      activated by arachidonic acid metabolites remain undefined. In rabbit thoracic
      aortic rings pretreated with indomethacin (10 micromol/L) and contracted with
      phenylephrine, arachidonic acid (0.1 to 100 micromol/L) induced concentration
      dependent relaxations. Maximal relaxations averaged 45+/-3% and were inhibited by
      increasing extracellular K+ (30 mmol/L, 15+/-5%; P<0.001) or incubation with
      apamin (100 nmol/L, 26+/-7%; P<0.05) but not incubation with charybdotoxin (100
      nmol/L, 41+/-5%). In aortic strips with an intact endothelium that were treated
      with phenylephrine, arachidonic acid (10 micromol/L) increased the membrane
      potential from -28.7+/-1.3 to -37.8+/-3.0 mV (P<0.01). Preincubation with apamin
      did not alter basal membrane potential but inhibited arachidonic acid-induced
      hyperpolarization (-31.5+/-1.5 mV). Incubation of rabbit aortic segments with
      apamin or charybdotoxin did not alter [14C]arachidonic acid metabolism. Whole
      cell outward K+ currents from isolated rabbit aortic smooth muscle cells averaged
      43.0+/-4.8 pA/pF at 60 mV and were significantly decreased to 35.7+/-4.2 pA/pF by
      apamin (P<0.001). Subsequent addition of charybdotoxin further decreased maximal
      currents to 14.4+/-2.3 pA/pF. Addition of 11,12,15-trihydroxyeicosatrienoic acid
      increased the outward whole-cell K+ current. In inside-out patches of aortic
      smooth muscle, apamin inhibited the calcium activation (100 to 300 nmol/L;
      P<0.001) of a small-conductance K+ channel (approximately 24 pS). These results
      suggest that arachidonic acid induces endothelium-dependent hyperpolarization and
      relaxation of rabbit aorta through activation of smooth muscle, apamin-sensitive
      K+ currents.

PMID- 14691200
TI  - Endothelium-derived nitric oxide modulates vascular action of aldosterone in
      renal arteriole.
AB  - We have recently demonstrated that aldosterone causes nongenomic vasoconstriction
      by activating phospholipase C (PLC) in the preglomerular afferent arteriole (Af
      Art). In the present study, we tested the hypothesis that endothelium modulates
      this vasoconstrictor action by releasing nitric oxide (NO). In addition, to study
      the post-PLC mechanism, we examined possible contributions of phosphoinositol
      hydrolysis products. Rabbit Af-Arts were microperfused at 60 mm Hg in vitro, and
      increasing doses of aldosterone (10(-10) to 10(-8) mol/L) were added to the bath
      and lumen. Aldosterone caused dose-dependent vasoconstriction (within 10
      minutes); significant (P<0.01) constriction was observed from 5x10(-9) mol/L, and
      at 10(-8) mol/L, intraluminal diameter decreased by 29%+/-3% (n=9). Disrupting
      the endothelium augmented vasoconstriction; significant constriction was observed
      from 10(-10) mol/L, and at 10(-8) mol/L, the diameter decreased by 38%+/-2%
      (n=6). NO synthesis inhibition reproduced this augmentation (n=7). Pretreatment
      with chelerythrine (10(-6) mol/L), a protein kinase C (PKC) inhibitor, slightly
      attenuated the constriction; aldosterone at 10(-8) mol/L now decreased the
      diameter by 18%+/-3% (n=7). However, in Af-Arts treated with thapsigargin (10(-6)
      mol/L) or dantrolene (3x10(-5) mol/L), which blocks inositol 1,4,5-triphosphate
      (IP3)-induced intracellular calcium release, aldosterone at 10(-8) mol/L
      decreased the diameter by only 9%+/-1% (n=6) or 9%+/-2% (n=5), respectively.
      These results demonstrate that in the Af-Art endothelium-derived NO modulates
      vasoconstrictor actions of aldosterone that are mediated by the activation of
      both IP3 and PKC pathways. Such vasoconstrictor actions of aldosterone may
      contribute to the development or aggravation of hypertension by elevating renal
      vascular resistance in cardiovascular diseases associated with endothelium
      dysfunction.

PMID- 14691202
TI  - Toxicogenomic analysis of aberrant gene expression in liver tumors and
      nontumorous livers of adult mice exposed in utero to inorganic arsenic.
AB  - Arsenic is a known human carcinogen. We have reported that brief exposure of
      pregnant C3H mice to arsenite in their drinking water during gestation induced
      hepatocellular carcinoma (HCC) in male offspring after they became adults. Tumor
      formation is typically associated with multiple gene expression changes, and this
      study examined aberrant gene expression associated with transplacental arsenic
      hepatocarcinogenesis. Liver tumors and nontumorous liver samples were taken at
      necropsy from adult male mice exposed in utero to either 42.5 or 85 ppm arsenic
      as sodium arsenite or unaltered water from day 8 to 18 of gestation. Total RNA
      was extracted and subjected to microarray analysis. Among 600 genes, arsenic
      induced HCC showed a higher rate of aberrant gene expression (>2-fold and p <
      0.05, 14%) than spontaneous tumors (7.8%). Overexpression of alpha-fetoprotein, c
      myc, cyclin D1, proliferation-associated protein PAG, and cytokeratin-18 were
      more dramatic in arsenic-induced HCC than spontaneous tumors. In nontumorous
      liver samples of arsenic-exposed animals, 60 genes (10%) were differentially
      expressed, including the increased expression of alpha-fetoprotein, c-myc,
      insulin-like growth factor binding protein-1, superoxide dismutase, glutathione S
      transferases, and CYP2A4, and the depressed expression of CYP7B1. Real-time RT
      PCR analysis largely confirmed these findings. This toxicogenomic analysis
      revealed several aberrant gene expression changes associated with transplacental
      arsenic carcinogenesis. It is indeed remarkable that expression changes occurred
      in adulthood even though arsenic exposure ended during gestation. Some of these
      aberrantly expressed genes could play a role in the development of arsenic
      induced tumors, at least in the liver.

PMID- 14691203
TI  - Age and dose dependency of the pharmacokinetics and metabolism of bisphenol A in
      neonatal sprague-dawley rats following oral administration.
AB  - Previous studies demonstrated the rapid clearance of bisphenol A (BPA) from blood
      following oral administration to adult rats with the principal metabolite being
      BPA-monoglucuronide (BPA-glucuronide). Since the ontogeny of glucuronyl
      transferases (GT) differs with age, the pharmacokinetics of BPA were studied in
      neonatal animals. (14)C-BPA was administered via gavage at 1 or 10 mg/kg body
      weight to rats at postnatal day (pnd) 4, pnd 7, pnd 21, or to 11 week old adult
      rats (10 mg/kg dose only). Blood (neonates and adults) and selected tissues
      (neonates) were collected at 0.25, 0.75, 1.5, 3, 6, 12, 18, and 24 h postdosing.
      BPA and BPA-glucuronide in the plasma were quantified by high-performance liquid
      chromatography; radioactivity in the plasma and tissues was quantified by liquid
      scintillation spectrometry. The data indicate that neonatal rats at all three
      ages metabolized BPA to BPA-glucuronide, although an age dependency in the number
      and concentration of plasma metabolites was observed, consistent with the
      ontogeny of GT. BPA-glucuronide and BPA concentrations in the plasma were greater
      in neonates than in adults, except at 24 h postdosing, suggesting an immaturity
      in the development of hepatic excretory function in neonatal rats. Nevertheless,
      the half-lives for the elimination of BPA-glucuronide in plasma were more rapid
      in neonatal animals than in adults, likely due to reduced microflora beta
      glucuronidase activity and an absence of enterohepatic recirculation. A dose
      dependency in the metabolism and pharmacokinetics of BPA administered to neonates
      was also observed with nearly complete metabolism of BPA to BPA-glucuronide (94
      100% of the plasma radioactivity) at a dose of 1 mg/kg. This was in contrast to
      finding up to 13 different plasma metabolites observed at the 10 mg/kg dose.
      These data indicate that, from early in neonatal life through pnd 21, there is
      sufficient GT activity in rats to efficiently metabolize BPA to its nonestrogenic
      metabolite at low doses.

PMID- 14691204
TI  - Interactions between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and hypoxia
      signaling pathways in zebrafish: hypoxia decreases responses to TCDD in zebrafish
      embryos.
AB  - The aryl hydrocarbon receptor (AHR) interacts with the aryl hydrocarbon receptor
      nuclear translocator (ARNT) to form a heterodimer that binds to promoters in
      target genes to alter transcription in response to xenobiotics such as 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). The ARNT protein also forms heterodimers with
      other proteins such as HIF-1alpha and HIF-2alpha to alter gene expression in
      response to low oxygen conditions. Because ARNT is shared between multiple
      signaling pathways it is possible that activation of one ARNT-requiring pathway
      could inhibit the activation of other pathways that depend on ARNT. One
      hypothesis to explain TCDD toxicity in early life stage fish is that TCDD
      activation of zfAHR2 sequesters zfARNT2 away from the hypoxia signaling pathway.
      To test this hypothesis we measured the ability of TCDD to prevent induction of
      heme oxygenase by hypoxia (40% saturation), as well as the ability of hypoxia to
      increase the sensitivity of zebrafish to the effects of TCDD during the first
      week of life. As a further test of the model we examined mutant zebrafish that
      lack zfARNT2 for phenotypes that resemble the effects of TCDD exposure. Our
      results demonstrate that sequestration of zfARNT2 is not causing TCDD toxicity.
      TCDD did not inhibit hypoxia induction of heme oxygenase, hypoxia and TCDD
      exposures were not additive in causing developmental toxicity, and mutant embryos
      that lack zfARNT2 do not develop defects mimicking TCDD toxicity. However, our
      results demonstrate some level of cross talk between the two pathways in the
      zebrafish embryo. Hypoxia decreased TCDD induction of zfCYP1A mRNA, and decreased
      the potency of TCDD in causing edema. It is not clear whether this is mediated
      through competition for zfARNT2, or through other mechanisms.

PMID- 14691205
TI  - Dietary fibers reduce the urinary excretion of 1-hydroxypyrene following
      intravenous administration of pyrene.
AB  - During biological monitoring of exposure to a chemical, a possible source of
      interindividual variability in the measurement of a urinary metabolite that
      undergoes enterohepatic cycling is the presence of dietary fiber in the
      gastrointestinal tract. This study examined the effect of diets containing either
      the insoluble fiber Alphacel (nonnutritive bulk cellulose) or the soluble pectin
      (from citrus fruit, MW 20,000-40,000). Five groups of male Sprague-Dawley rats
      received one of the following diets: poor (5% w/w) or rich (15% w/w) in Alphacel,
      poor (5% w/w) or rich (15% w/w) in pectin, or no fiber (NF). Five micromol/kg of
      pyrene was administered by iv injection immediately after feeding the animals
      with their respective diet, and urine and feces collections started for the
      determination of 1-hydroxypyrene (1-OHP), a metabolite of pyrene. The type of
      fiber had no influence on the results. The rats receiving diets both poor and
      rich in fiber excreted less 1-OHP (18 +/- 8 and 15 +/- 7 pmol per g of rat,
      respectively) in the 24-h urine samples than the NF group (28 +/- 6 pmol/g).
      There was a nonstatistically significant trend towards increased fecal and total
      (urinary + fecal) 1-OHP excretion with increasing amount of fiber in the diet. An
      in vitro experiment showed an inverse correlation (r(2) = 0.98) between the
      amount of Alphacel in suspension in a 1-OHP aqueous solution and the recovery of
      1-OHP from the soluble fraction. The reduction in urinary output of the
      metabolite due to fiber reaching approximately 40% may contribute to its
      interindividual variability observed in occupational and environmental studies.

PMID- 14691206
TI  - Evaluation of fish early life-stage toxicity models of chronic embryonic
      exposures to complex polycyclic aromatic hydrocarbon mixtures.
AB  - Polycyclic aromatic hydrocarbons (PAHs) can cause a variety of effects in early
      life-stages of fish that have been chronically exposed as embryos, including
      mortality, deformities, and edemas. Mechanistic models of the chronic toxicity of
      complex mixtures of PAHs in fish have not been reported, with the exception of a
      previously untested model based on the lipids of fish as the site of action and
      toxicity caused through a narcosis mechanism. Four mechanism-based models of the
      chronic toxicity of embryonic exposures to complex mixtures of petrogenic PAHs in
      two species of fish, Pacific herring and pink salmon, were evaluated using a
      toxic-units approach: narcosis, aryl hydrocarbon receptor (AhR) agonism, alkyl
      phenanthrene toxicity, and combined toxicity. Alkyl phenanthrenes were the
      predominant PAH constituent determining early life-stage toxicity in both herring
      and salmon. The alkyl phenanthrene model had 67 to 80% accuracy in predicting the
      absence or presence of significant early life-stage toxicity, compared with a 40
      to 50% accuracy and general underprediction of toxicity with the narcosis model.
      PAHs with high relative AhR affinity did not appear to contribute substantially
      to the observed early life-stage toxicity because of low concentrations of the
      most potent AhR agonists. Narcosis appeared to primarily contribute to embryo
      mortality and to be predominantly controlled by the concentration of
      naphthalenes. Except for the highest PAH exposure to herring, the primary toxic
      unit contribution to the combined toxicity model was alkyl phenanthrene toxicity
      to both herring and salmon. We recommend the continued use of total PAHs as a
      metric of exposure until mechanistic models have been further evaluated.

PMID- 14691207
TI  - Thioredoxin and its role in toxicology.
AB  - Thioredoxins (Trx) are members of an evolutionarily conserved family of redox
      active proteins containing a conserved active site dithiol motif. Trx supports
      diverse reduction reactions, including several of direct toxicologic interest,
      but relatively little information is available concerning the roles of Trx under
      specific toxicologic conditions. Accumulating evidence suggests that Trx serves a
      partially overlapping and highly complementary role to the glutathione (GSH)
      system in protecting against toxicity. GSH and Trx both function in the reduction
      of peroxides through the action of multiple GSH peroxidases and Trx peroxidases
      (peroxiredoxins), respectively. However, GSH is a small molecule that is present
      at millimolar concentrations, thereby providing a potential mechanism for
      elimination of alkylating electrophiles. In contrast, even though Trx is only
      present at micromolar or submicromolar concentrations, its dithiol motif makes it
      suited to reverse oxidative changes to proteins, including reduction of protein
      disulfides, methioninyl sulfoxides, and cysteinyl sulfenic acids. Moreover, Trx
      functions in redox-sensitive signal transduction, transcriptional activation of
      stress response genes, ribonucleotide reduction in synthesis of
      deoxyribonucleotides for DNA repair, and post-injury cell proliferation.
      Molecular studies show that the predominant cytoplasmic/nuclear form, Trx-1, and
      the mitochondrial form, Trx-2, both protect against oxidative stress, that both
      are essential for embryonic development, and that Trx-1 is inducible in response
      to oxidative stress. Because of the differences between GSH and Trx in
      distribution, catalytic activities and reactivities with electrophiles,
      particularly with the important role to be played by glutathione S-transferases,
      considerable research is needed to clarify their respective roles in protection
      against specific toxicologic conditions.

PMID- 14691208
TI  - Extended histopathology in immunotoxicity testing: interlaboratory validation
      studies.
AB  - There has been considerable interest in the use of expanded histopathology as a
      primary screen for immunotoxicity assessment. To determine the utility of a
      semiquantitative histopathology approach for examining specific structural and
      architectural changes in lymphoid tissues, a validation effort was initiated.
      This study addresses the interlaboratory reproducibility of extended
      histopathology, using tissues from studies of ten test chemicals and both
      negative and positive controls from the National Toxicology Program's
      immunotoxicology testing program. We examined the consistency between experienced
      toxicologic pathologists, who had varied expertise in immunohistopathology in
      identifying lesions in immune tissues, and in the sensitivity of the individual
      and combined histopathological endpoints to detect chemical effects and dose
      response. Factor analysis was used to estimate the association of each
      pathologist with a so-called "common factor" and analysis-of-variance methods
      were used to evaluate biases. Agreement between pathologists was highest in the
      thymus, in particular, when evaluating cortical cellularity of the thymus; good
      in spleen follicular cellularity and in spleen and lymph node-germinal center
      development; and poorest in spleen red-pulp changes. In addition, the ability to
      identify histopathological change in lymphoid tissues was dependent upon the
      experience/training that the individual pathologist possessed in examining
      lymphoid tissue and the apparent severity of the specific lesion.

PMID- 14691209
TI  - Potent estrogenic metabolites of bisphenol A and bisphenol B formed by rat liver
      S9 fraction: their structures and estrogenic potency.
AB  - We previously demonstrated that the estrogenicity of either bisphenol A [BPA; 2,2
      bis(4-hydroxyphenyl)propane] or bisphenol B [BPB; 2,2-bis(4-hydroxyphenyl)butane]
      was increased several times after incubation with rat liver S9 fraction
      (Yoshihara et al., 2001). This metabolic activation, requiring both microsomal
      and cytosolic fractions, was observed with not only rat liver, but also human,
      monkey, and mouse liver S9 fractions. To characterize the active metabolites of
      BPA and BPB, we investigated the structures of the isolated active metabolites by
      negative mode LC/MS/MS and GC/MS. The active metabolite of BPA gave a negative
      mass peak at [M-H](-) 267 on LC/MS and a single daughter ion at m/z 133 on MS/MS
      analysis, suggesting an isopropenylphenol dimer structure. Finally, this active
      metabolite was confirmed to be identical with authentic 4-methyl-2,4-bis(p
      hydroxyphenyl)pent-1-ene (MBP) by means of various instrumental analyses. The
      corresponding peaks of the BPB metabolite were [M-H](-) 295 and m/z 147,
      respectively, suggesting an isobutenylphenol dimer structure. Further,
      coincubation of BPA and BPB with rat liver S9 afforded an additional active
      metabolite(s), which gave a negative mass peak at [M-H](-) 281 and two daughter
      ion peaks at m/z 133 and m/z 147 on MS/MS analysis. These results strongly
      suggest that the active metabolite of either BPA or BPB might be formed by
      recombination of a radical fragment, a one-electron oxidation product of carbon
      phenyl bond cleavage. It is noteworthy that the estrogenic activity of MBP, the
      active metabolite of BPA, is much more potent than that of the parent BPA in
      several assays, including two reporter assays using a recombinant yeast
      expressing human estrogen receptor alpha and an MCF-7-transfected firefly
      luciferase plasmid.

PMID- 14691210
TI  - Bromodichloromethane inhibits human placental trophoblast differentiation.
AB  - Epidemiological data suggest an association between exposures to
      bromodichloromethane (BDCM), a trihalomethane found in drinking water as a result
      of drinking water disinfection, and an increased risk of spontaneous abortion. We
      previously hypothesized that BDCM targets the placenta and showed that the
      secretion of chorionic gonadotrophin (CG) was reduced in primary cultures of
      human term syncytiotrophoblasts exposed to BDCM. In the present study we extend
      this observation by evaluating the effects of BDCM on the morphological
      differentiation of mononucleated cytotrophoblast cells to multinucleated
      syncytiotrophoblast-like colonies. Addition of BDCM to cytotrophoblast cultures
      inhibited the subsequent formation of multinucleated colonies in a dose-dependent
      manner, as determined by immunocytochemical staining for desmosomes and nuclei.
      The effect was seen at BDCM concentrations between 0.02 and 2 mM and was
      confirmed by quantitative image analysis. Secretion of bioactive and
      immunoreactive chorionic gonadotropin was also significantly inhibited in a dose
      dependent manner under these culture conditions, and cellular levels of CG were
      also reduced. Trophoblast viability was not compromised by exposure to BDCM. We
      conclude that BDCM disrupts syncytiotrophoblast formation and inhibits CG
      secretion in vitro. Although other tissue targets are not ruled out, these data
      substantiate the idea that BDCM targets the placenta and could have implications
      for understanding the adverse pregnancy outcomes associated with BDCM exposure in
      humans.

PMID- 14691211
TI  - Modulation of AhR-mediated CYP1A1 mRNA and EROD activities by 17beta-estradiol
      and dexamethasone in TCDD-induced H411E cells.
AB  - TCDD elicits a variety of species- and organ-specific pathological consequences.
      The differential toxicities are thought to relate to the de novo modulation of
      TCDD action by endogenous hormones. Previous studies from this laboratory
      demonstrated a dose- and time-dependent induction of CYP1A1 expression and 7
      ethoxyresorufin-O-deethylase (EROD) activities in H4IIE cells by picomolar levels
      of TCDD treatment. In this study, we examined the hormonal modulation of TCDD
      elicited AhR-mediated biochemical responses. Lipid-soluble hormones, 17beta
      estradiol (E(2)), diethylstilbestrol (DES), testosterone (T), 5alpha
      dihydrotestosterone (DHT), dexamethasone (DEX), and T(3), were studied for their
      possible interactions with the TCDD-mediated effects. Our results showed that
      CYP1A1 expression and EROD activities induced by TCDD were potentiated or
      suppressed, respectively, by DEX or E(2)/DES treatment. Other tested hormones,
      however, had no significant effect. Using a receptor antagonist (RU486), DEX
      mediated potentiation of TCDD-elicited EROD activity was completely abolished.
      E(2)-mediated suppression, however, was not affected by cotreatment with the
      estrogen receptor antagonists, 4-hydroxytamoxifen or ICI 182780. Taking a step
      further to dissect the possible mechanisms involved, with the aid of
      cycloheximide (CHX), DEX-mediated potentiation was found to depend on the
      posttranscriptional process. The DEX pretreatment study indicated that the
      potentiation was a time-dependent process. In contrast, E(2)-mediated suppression
      did not rely on the synthesis of protein factors. Presumably it might hinder the
      formation of the activated TCDD/AhR complex and so the subsequent binding on DRE.

PMID- 14691213
TI  - Chlorpyrifos induces apoptosis in rat cortical neurons that is regulated by a
      balance between p38 and ERK/JNK MAP kinases.
AB  - Chlorpyrifos, an acetylcholinesterase (AChE) inhibitor, is a widely used
      organophosphate pesticide. Recent concern has focused on its neurotoxicity that
      is not attributable to AChE inhibition. Here, we report that chlorpyrifos and
      chlorpyrifos-oxon, but not 3,5,6-trichloro-2-pyridinol (TCP; the breakdown
      product of chlorpyrifos and chlorpyrifos-oxon), induce apoptosis in primary
      cortical neurons cultured from embryonic day 17 or newborn rats. It is generally
      agreed that chlorpyrifos-oxon is approximately three orders of magnitude more
      potent than chlorpyrifos in inhibition of brain acetylcholinesterase activity.
      However, our data demonstrate that chlorpyrifos-oxon is only slightly more potent
      than chlorpyrifos in inducing apoptosis. This indicates that chlorpyrifos-induced
      apoptosis may occur independently of AChE inhibition, although AChE activity was
      not measured in this study. Furthermore, chlorpyrifos activates the ERK1/2 and
      p38 MAP kinases. Surprisingly, blocking ERK1/2 activation by the MEK inhibitor
      SL327 caused a small but statistically significant inhibition of apoptosis, while
      blocking p38 with SB202190 significantly accelerated apoptosis induced by
      chlorpyrifos. This suggests a pro- and anti-apoptotic role for ERK1/2 and p38,
      respectively. Although chlorpyrifos did not stimulate total JNK activity, it
      caused a sustained activation of a sub-pool of JNK in the nucleus and stimulated
      phosphorylation of c-Jun, a downstream target of JNK. Transient expression of a
      dominant negative c-Jun mutant inhibited chlorpyrifos-induced apoptosis,
      suggesting a role for JNK and JNK-mediated transcription in this cell death.
      Together, our data suggest apoptosis as a novel toxic endpoint of chlorpyrifos
      neurotoxicity in the brain that may be independent of AChE inhibition.
      Furthermore, activation of the ERK1/2 and JNK MAP kinases contributes to, while
      activation of the p38 MAP kinase counteracts chlorpyrifos-induced apoptosis in
      cortical neurons.

PMID- 14691214
TI  - DNA adduct formation in precision-cut rat liver and lung slices exposed to
      benzo[a]pyrene.
AB  - Chemical-DNA adducts provide an integrated measure of exposure, absorption,
      bioactivation, detoxification, and DNA repair following exposure to a genotoxic
      agent. Benzo[a]pyrene (BaP), a prototypical polycyclic aromatic hydrocarbon
      (PAH), can be bioactivated by cytochrome P-450s (CYPs) and epoxide hydrolase to
      genotoxic metabolites which form covalent adducts with DNA. In this study, we
      utilized precision-cut rat liver and lung slices exposed to BaP to investigate
      tissue-specific differences in chemical absorption and formation of DNA adducts.
      To investigate the contribution of bioactivating CYPs (such as CYP1A1 and CYP1B1)
      on the formation of BaP-DNA adducts, animals were also pretreated in vivo with
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) prior to in vitro incubation
      of tissue slices with BaP. Furthermore, the tissue distribution of BaP and BaP
      DNA adduct levels from in vivo studies were compared with those from the in vitro
      tissue slice experiments. The results indicate a time- and concentration
      dependent increase in tissue-associated BaP following exposure of rat liver and
      lung tissue slices to BaP in vitro, with generally higher levels of BaP retained
      in lung tissue. Furthermore, rat liver and lung slices metabolized BaP to
      reactive intermediates that formed covalent adducts with DNA. Total BaP-DNA
      adducts increased with concentration and incubation time. Adduct levels (fmol
      adduct/microg DNA) in lung slices were greater than liver at all doses. Liver
      slices contained one major and two minor adducts, while lung slices contained two
      major and 3 minor adducts. The tissue-specific qualitative profile of these
      adducts in tissue slices was similar to that observed from in vivo studies,
      further validating the use of this model. Pretreatment of animals with TCDD prior
      to in vitro incubation with BaP potentiated the levels of DNA adduct formation.
      TCDD pretreatment altered the adduct distribution in lung but not in liver
      slices. Together, the results suggest that tissue-specific qualitative and
      quantitative differences in BaP-DNA adducts could contribute to the lung being a
      target tissue for BaP carcinogenesis. Furthermore, the results validate the use
      of precision-cut tissue slices incubated in dynamic organ culture as a useful
      model for the study of chemical-DNA adduct formation.

PMID- 14691215
TI  - An in vitro human cell-based assay to rank the relative immunogenicity of
      proteins.
AB  - A method to rank proteins based on their relative immunogenicity has been
      devised. A statistical analysis of peptide-specific responses in large human
      donor pools provides a structure index value metric that ranked four industrial
      enzymes in the order determined by both mouse and guinea pig exposure models. The
      ranking method also compared favorably with human sensitization rates measured in
      occupationally exposed workers. Structure index values for other proteins known
      to cause immune responses in humans were also determined and found to be higher
      than the value determined for human beta2-microglobulin. Using values from known
      immunogenic and putative nonimmunogenic proteins, a cut-off value was
      established. The structure index value calculation provides a comparative method
      to predict subsequent immunogenicity on a human population basis without the need
      to use animal models. Information provided by this assay can be used in the early
      development of protein therapies and other protein-based applications to select
      or create reduced immunogenicity variants.

PMID- 14691216
TI  - Effect of multiple symmetries on the association of R67 DHFR subunits bearing
      interfacial complementing mutations.
AB  - It was shown previously that complementation could be a powerful mean to probe
      protein-protein interactions in the normally tetrameric R67 DHFR. Indeed, mixing
      complementing inactive dimeric mutants produced active heterotetramers. This
      approach turned a homo-oligomer into a hetero-oligomer and thus allowed the use
      of combinatorial assays, a subtle analysis of the association forces, and a
      precise determination of the equilibrium dissociation constants (K(D)) by
      titrimetry. However, for some of the complementing pairs, the experimental data
      implied multiple equilibria involving heterodimers, although no monomers could be
      detected. Thus, the reactions involved had to be identified to elaborate a
      suitable model to determine the K(D) of those pairs correctly. That model
      suggested that homodimers associated rapidly before the protomers could be
      redistributed in a multiple equilibrium system. Kinetic data confirmed that view.
      The association data at equilibrium were analyzed by multiple curve fitting with
      all plausible combinations of parameters. This gave a confidence interval for
      K(D) that is safer than the usual 67% or 90% confidence interval. Finally, the
      K(D) of one specific reaction, the dissociation of a heterotetramer with the
      relevant symmetry into two homodimers could be determined with the relevant model
      for each complementing pair, although multiple equilibria were present. These
      K(D) can thus be used as a set of references data to test and improve theoretical
      methods such as association free energy calculations.

PMID- 14691217
TI  - Using surface envelopes for discrimination of molecular models.
AB  - Shape information about macromolecules is increasingly available but is difficult
      to use in modeling efforts. We demonstrate that shape information alone can often
      distinguish structural models of biological macromolecules. By using a data
      structure called a surface envelope (SE) to represent the shape of the molecule,
      we propose a method that generates a fitness score for the shape of a particular
      molecular model. This score correlates well with root mean squared deviation
      (RMSD) of the model to the known test structures and can be used to filter models
      in decoy sets. The scoring method requires both alignment of the model to the SE
      in three-dimensional space and assessment of the degree to which atoms in the
      model fill the SE. Alignment combines a hybrid algorithm using principal
      components and a previously published iterated closest point algorithm. We test
      our method against models generated from random atom perturbation from crystal
      structures, published decoy sets used in structure prediction, and models created
      from the trajectories of atoms in molecular modeling runs. We also test our
      alignment algorithm against experimental electron microscopic data from rice
      dwarf virus. The alignment performance is reliable, and we show a high
      correlation between model RMSD and score function. This correlation is stronger
      for molecular models with greater oblong character (as measured by the ratio of
      largest to smallest principal component).

PMID- 14691218
TI  - Variability-based sequence alignment identifies residues responsible for
      functional differences in alpha and beta tubulin.
AB  - alpha and beta Tubulin are well-characterized paralogs with similar structures
      and functions. We quantify the variability of every amino acid position in both
      tubulins from the aligned sequences of their numerous known orthologs. By
      aligning the variability profiles, we identify residues that differ significantly
      in variability between alpha and beta tubulin. Most of these residues are part of
      well-defined secondary structures and are clustered around the nucleotide binding
      pocket, the site of greatest functional difference between the two paralogs. The
      remaining residues of large difference in variability are located in the N
      terminal loop between H1 and S2. We therefore predict that certain residues in
      this unstructured region also contribute to a functional difference between alpha
      and beta tubulin. Furthermore, we find the most restrictive variability-based
      alignment is nearly identical to the true structure-based alignment. Thus, by
      using a stringent variability-based alignment to approximate the true alignment,
      the method introduced here may predict sites of functional distinction between
      paralogous proteins even in the absence of structural information.

PMID- 14691219
TI  - Effect of the N3 residue on the stability of the alpha-helix.
AB  - N3 is the third position from the N terminus in the alpha-helix with helical
      backbone dihedral angles. All 20 amino acids have been placed in the N3 position
      of a synthetic helical peptide (CH(3)CO-[AAX AAAAKAAAAKAGY]-NH(2)) and the helix
      content measured by circular dichroism spectroscopy at 273 K. The dependence of
      peptide helicity on N3 residue identity has been used to determine a free energy
      scale by analysis with a modified Lifson-Roig helix coil theory that includes a
      parameter for the N3 energy (n3). The most stabilizing residues at N3 in rank
      order are Ala, Glu, Met/Ile, Leu, Lys, Ser, Gln, Thr, Tyr, Phe, Asp, His, and
      Trp. Free energies for the most destabilizing residues (Cys, Gly, Asn, Arg, and
      Pro) could not be fitted. The results correlate with N1, N2, and helix interior
      energies and not at all with N-cap preferences. This completes our work on
      studying the structural and energetic preferences of the amino acids for the N
      terminal positions of the alpha-helix. These results can be used to rationally
      modify protein stability, help design helices, and improve prediction of helix
      location and stability.

PMID- 14691220
TI  - Thermodynamics and stability of a beta-sheet complex: molecular dynamics
      simulations on simplified off-lattice protein models.
AB  - We have performed discontinuous molecular dynamics simulations of the
      thermodynamics and stability of a tetrameric beta-sheet complex that contains
      four identical four-stranded antiparallel beta-sheet peptides. The potential used
      in the simulation is a hybrid Go-type potential characterized by the bias gap
      parameter g, an artificial measure of the preference of a model protein for its
      native state, and the intermolecular contact parameter eta, which measures the
      ratio of intermolecular to intramolecular native attractions. Despite the
      simplicity of the model, a complex set of thermodynamic transitions for the beta
      sheet complex is revealed that shows there are three distinct oligomer (partially
      ordered, ordered, and highly ordered beta-sheet complex) states and four
      noninteracting monomers phases. The thermodynamic properties of the three
      oligomer states strongly depend on both the size of the intermolecular contact
      parameter eta and the temperature. The partially ordered beta-sheet complex is
      made up of four ordered globules and is observed at intermediate to large eta at
      high temperatures. The ordered beta-sheet complex contains four native beta
      sheets and is located at small to intermediate eta at low temperatures in the
      phase diagram. The highly ordered beta-sheet complex has fully-stiff beta-sheet
      strands, the same as the global energy minimum structure, and is observed for all
      eta at low temperatures.

PMID- 14691221
TI  - Detection of homologous proteins by an intermediate sequence search.
AB  - We developed a variant of the intermediate sequence search method (ISS(new)) for
      detection and alignment of weakly similar pairs of protein sequences. ISS(new)
      relates two query sequences by an intermediate sequence that is potentially
      homologous to both queries. The improvement was achieved by a more robust overlap
      score for a match between the queries through an intermediate. The approach was
      benchmarked on a data set of 2369 sequences of known structure with insignificant
      sequence similarity to each other (BLAST E-value larger than 0.001); 2050 of
      these sequences had a related structure in the set. ISS(new) performed
      significantly better than both PSI-BLAST and a previously described intermediate
      sequence search method. PSI-BLAST could not detect correct homologs for 1619 of
      the 2369 sequences. In contrast, ISS(new) assigned a correct homolog as the top
      hit for 121 of these 1619 sequences, while incorrectly assigning homologs for
      only nine targets; it did not assign homologs for the remainder of the sequences.
      By estimate, ISS(new) may be able to assign the folds of domains in approximately
      29,000 of the approximately 500,000 sequences unassigned by PSI-BLAST, with 90%
      specificity (1 - false positives fraction). In addition, we show that the 15
      alignments with the most significant BLAST E-values include the nearly best
      alignments constructed by ISS(new).

PMID- 14691222
TI  - Differences in aggregation properties of three site-specific mutants of
      recombinant human stefin B.
AB  - We describe expression, purification, and characterization of three site-specific
      mutants of recombinant human stefin B: H75W, P36G, and P79S. The far- and near-UV
      CD spectra have shown that they have similar secondary and tertiary structures to
      the parent protein. The elution on gel-filtration suggests that recombinant human
      stefin B and the P36G variant are predominantly monomers, whereas the P79S
      variant is a dimer. ANS dye binding, reflecting exposed hydrophobic patches, is
      highest for the P36G variant, both at pH 5 and 3. ANS dye binding also is
      increased for stefin B and the other two variants at pH 3. Under the chosen
      conditions the highest tendency to form amyloid fibrils has been shown for the
      recombinant human stefin B. The P79S variant demonstrates a longer lag phase and
      a lower rate of fibril formation, while the P36G variant is most prone to
      amorphous aggregation. This was demonstrated by ThT fluorescence as a function of
      time and by transmission electron microscopy.

PMID- 14691223
TI  - Protein flexibility and intrinsic disorder.
AB  - Comparisons were made among four categories of protein flexibility: (1) low-B
      factor ordered regions, (2) high-B-factor ordered regions, (3) short disordered
      regions, and (4) long disordered regions. Amino acid compositions of the four
      categories were found to be significantly different from each other, with high-B
      factor ordered and short disordered regions being the most similar pair. The high
      B-factor (flexible) ordered regions are characterized by a higher average
      flexibility index, higher average hydrophilicity, higher average absolute net
      charge, and higher total charge than disordered regions. The low-B-factor regions
      are significantly enriched in hydrophobic residues and depleted in the total
      number of charged residues compared to the other three categories. We examined
      the predictability of the high-B-factor regions and developed a predictor that
      discriminates between regions of low and high B-factors. This predictor achieved
      an accuracy of 70% and a correlation of 0.43 with experimental data,
      outperforming the 64% accuracy and 0.32 correlation of predictors based solely on
      flexibility indices. To further clarify the differences between short disordered
      regions and ordered regions, a predictor of short disordered regions was
      developed. Its relatively high accuracy of 81% indicates considerable differences
      between ordered and disordered regions. The distinctive amino acid biases of high
      B-factor ordered regions, short disordered regions, and long disordered regions
      indicate that the sequence determinants for these flexibility categories differ
      from one another, whereas the significantly-greater-than-chance predictability of
      these categories from sequence suggest that flexible ordered regions, short
      disorder, and long disorder are, to a significant degree, encoded at the primary
      structure level.

PMID- 14691224
TI  - Tubulin equilibrium unfolding followed by time-resolved fluorescence and
      fluorescence correlation spectroscopy.
AB  - The pathway for the in vitro equilibrium unfolding of the tubulin heterodimer by
      guanidinium chloride (GdmCl) has been studied using several spectroscopic
      techniques, specifically circular dichroism (CD), two-photon Fluorescence
      Correlation Spectroscopy (FCS), and time-resolved fluorescence, including
      lifetime and dynamic polarization. The results show that tubulin unfolding is
      characterized by distinct processes that occur in different GdmCl concentration
      ranges. From 0 to 0.5 M GdmCl, a slight alteration of the tubulin heterodimer
      occurs, as evidenced by a small, but reproducible increase in the rotational
      correlation time of the protein and a sharp decrease in the secondary structure
      monitored by CD. In the range 0.5-1.5 M GdmCl, significant decreases in the
      steady-state anisotropy and average lifetime of the intrinsic tryptophan
      fluorescence occur, as well as a decrease in the rotational correlation time,
      from 48 to 26 nsec. In the same GdmCl range, the number of protein molecules
      (labeled with Alexa 488), as determined by two-photon FCS measurements, increases
      by a factor of two, indicating dissociation of the tubulin dimer into monomers.
      From 1.5 to 4 M GdmCl, these monomers unfold, as evidenced by the continual
      decrease in the tryptophan steady-state anisotropy, average lifetime, and
      rotational correlation time, concomitant with secondary structural changes. These
      results help to elucidate the unfolding pathway of the tubulin heterodimer and
      demonstrate the value of FCS measurements in studies on oligomeric protein
      systems.

PMID- 14691225
TI  - Thermostability of multidomain proteins: elongation factors EF-Tu from
      Escherichia coli and Bacillus stearothermophilus and their chimeric forms.
AB  - Recombinant mesophilic Escherichia coli (Ec) and thermophilic Bacillus
      stearothermophilus (Bst) elongation factors EF-Tus, their isolated G-domains, and
      six chimeric EF-Tus composed of domains of either EF-Tu were prepared, and their
      GDP/GTP binding activities and thermostability were characterized. BstEF-Tu and
      BstG-domain bound GDP and GTP with affinities in nanomolar and submicromolar
      ranges, respectively, fully comparable with those of EcEF-Tu. In contrast, the
      EcG-domain bound the nucleotides with much lower, micromolar affinities. The
      exchange of domains 2 and 3 had essentially no effect on the GDP-binding
      activity; all complexes of chimeric EF-Tus with GDP retained K(d) values in the
      nanomolar range. The final thermostability level of either EF-Tu was the result
      of a cooperative interaction between the G-domains and domains 2 + 3. The G
      domains set up a "basic" level of the thermostability, which was approximately 20
      degrees C higher with the BstG-domain than with the EcG-domain. This correlated
      with the growth temperature optimum difference of both bacteria and two distinct
      thermostabilization features of the BstG-domain: an increase of charged residues
      at the expense of polar uncharged residues (CvP bias), and a decrease in the
      nonpolar solvent-accessible surface area. Domains 2 + 3 contributed by further
      stabilization of alpha-helical regions and, in turn, the functions of the G
      domains to the level of the respective growth temperature optima. Their
      contributions were similar irrespective of their origin but, with Ecdomains 2 +
      3, dependent on the guanine nucleotide binding state. It was lower in the GTP
      conformation, and the mechanism involved the destabilization of the alpha-helical
      regions of the G-domain by Ecdomain 2.

PMID- 14691226
TI  - On the analysis of membrane protein circular dichroism spectra.
AB  - Analysis of circular dichroism spectra of proteins provides information about
      protein secondary structure. Analytical methods developed for such an analysis
      use structures and spectra of a set of reference proteins. The reference protein
      sets currently in use include soluble proteins with a wide range of secondary
      structures, and perform quite well in analyzing CD spectra of soluble proteins.
      The utility of soluble protein reference sets in analyzing membrane protein CD
      spectra, however, has been questioned in a recent study that found current
      reference protein sets to be inadequate for analyzing membrane proteins. We have
      examined the performance of reference protein sets available in the CDPro
      software package for analyzing CD spectra of 13 membrane proteins with available
      crystal structures. Our results indicate that the reference protein sets
      currently available for CD analysis perform reasonably well in analyzing membrane
      protein CD spectra, with performance indices comparable to those for soluble
      proteins. Soluble + membrane protein reference sets, which were constructed by
      combining membrane proteins with soluble protein reference sets, gave improved
      performance in both soluble and membrane protein CD analysis.

PMID- 14691227
TI  - Understanding the determinants of stability and folding of small globular
      proteins from their energetics.
AB  - The results of minimal model calculations indicate that the stability and the
      kinetic accessibility of the native state of small globular proteins are
      controlled by few "hot" sites. By means of molecular dynamics simulations around
      the native conformation, which describe the protein and the surrounding solvent
      at the all-atom level, an accurate and compact energetic map of the native state
      of the protein is generated. This map is further simplified by means of an
      eigenvalue decomposition. The components of the eigenvector associated with the
      lowest eigenvalue indicate which hot sites are likely to be responsible for the
      stability and for the rapid folding of the protein. The comparison of the results
      of the model with the findings of mutagenesis experiments performed for four
      small proteins show that the eigenvalue decomposition method is able to identify
      between 60% and 80% of these (hot) sites.

PMID- 14691228
TI  - Protein folding by the effects of macromolecular crowding.
AB  - Unfolded states of ribonuclease A were used to investigate the effects of
      macromolecular crowding on macromolecular compactness and protein folding. The
      extent of protein folding and compactness were measured by circular dichroism
      spectroscopy, fluorescence correlation spectroscopy, and NMR spectroscopy in the
      presence of polyethylene glycol (PEG) or Ficoll as the crowding agent. The
      unfolded state of RNase A in a 2.4 M urea solution at pH 3.0 became native in
      conformation and compactness by the addition of 35% PEG 20000 or Ficoll 70. In
      addition, the effects of macromolecular crowding on inert macromolecule
      compactness were investigated by fluorescence correlation spectroscopy using
      Fluorescence-labeled PEG as a test macromolecule. The size of Fluorescence
      labeled PEG decreased remarkably with an increase in the concentration of PEG
      20000 or Ficoll 70. These results show that macromolecules are favored compact
      conformations in the presence of a high concentration of macromolecules and
      indicate the importance of a crowded environment for the folding and
      stabilization of globular proteins. Furthermore, the magnitude of the effects on
      macromolecular crowding by the different sizes of background molecules was
      investigated. RNase A and Fluorescence-labeled PEG did not become compact, and
      had folded conformation by the addition of PEG 200. The effect of the chemical
      potential on the compaction of a test molecule in relation to the relative sizes
      of the test and background molecules is also discussed.

PMID- 14691229
TI  - Expression and biochemical characterization of two small heat shock proteins from
      the thermoacidophilic crenarchaeon Sulfolobus tokodaii strain 7.
AB  - We expressed and characterized two sHsps, StHsp19.7 and StHsp14.0, from a
      thermoacidophilic crenarchaeon, Sulfolobus tokodaii strain 7. StHsp19.7 forms a
      filamentous structure consisting of spherical particles and lacks molecular
      chaperone activity. Fractionation of Sulfolobus extracts by size exclusion
      chromatography with immunoblotting indicates that StHsp19.7 exists as a
      filamentous structure in vivo. On the other hand, StHsp14.0 exists as a spherical
      oligomer like other sHsps. It showed molecular chaperone activity to protect
      thermophilic 3-isopropylmalate dehydrogenase (IPMDH) from thermal aggregation at
      87 degrees C. StHsp14.0 formed variable-sized complexes with denatured IPMDH at
      90 degrees C. Using StHsp14.0 labeled with fluorescence or biotin probe and
      magnetic separation, subunit exchanges between complexes were demonstrated. This
      is the first report on the filament formation of sHsp and also the high molecular
      chaperone activity of thermophilic archaeal sHsps.

PMID- 14691230
TI  - N-linked glycosylation of dipeptidyl peptidase IV (CD26): effects on enzyme
      activity, homodimer formation, and adenosine deaminase binding.
AB  - The type II transmembrane serine protease dipeptidyl peptidase IV (DPPIV), also
      known as CD26 or adenosine deaminase binding protein, is a major regulator of
      various physiological processes, including immune, inflammatory, nervous, and
      endocrine functions. It has been generally accepted that glycosylation of DPPIV
      and of other transmembrane dipeptidyl peptidases is a prerequisite for enzyme
      activity and correct protein folding. Crystallographic studies on DPPIV reveal
      clear N-linked glycosylation of nine Asn residues in DPPIV. However, the
      importance of each glycosylation site on physiologically relevant reactions such
      as dipeptide cleavage, dimer formation, and adenosine deaminase (ADA) binding
      remains obscure. Individual Asn-->Ala point mutants were introduced at the nine
      glycosylation sites in the extracellular domain of DPPIV (residues 39-766).
      Crystallographic and biochemical data demonstrate that N-linked glycosylation of
      DPPIV does not contribute significantly to its peptidase activity. The kinetic
      parameters of dipeptidyl peptidase cleavage of wild-type DPPIV and the N
      glycosylation site mutants were determined by using Ala-Pro-AFC and Gly-Pro-pNA
      as substrates and varied by <50%. DPPIV is active as a homodimer. Size-exclusion
      chromatographic analysis showed that the glycosylation site mutants do not affect
      dimerization. ADA binds to the highly glycosylated beta-propeller domain of
      DPPIV, but the impact of glycosylation on binding had not previously been
      determined. Our studies indicate that glycosylation of DPPIV is not required for
      ADA binding. Taken together, these data indicate that in contrast to the
      generally accepted view, glycosylation of DPPIV is not a prerequisite for
      catalysis, dimerization, or ADA binding.

PMID- 14691231
TI  - Intrasteric control of AMPK via the gamma1 subunit AMP allosteric regulatory
      site.
AB  - AMP-activated protein kinase (AMPK) is a alphabetagamma heterotrimer that is
      activated in response to both hormones and intracellular metabolic stress
      signals. AMPK is regulated by phosphorylation on the alpha subunit and by AMP
      allosteric control previously thought to be mediated by both alpha and gamma
      subunits. Here we present evidence that adjacent gamma subunit pairs of CBS
      repeat sequences (after Cystathionine Beta Synthase) form an AMP binding site
      related to, but distinct from the classical AMP binding site in phosphorylase,
      that can also bind ATP. The AMP binding site of the gamma(1) CBS1/CBS2 pair,
      modeled on the structures of the CBS sequences present in the inosine
      monophosphate dehydrogenase crystal structure, contains three arginine residues
      70, 152, and 171 and His151. The yeast gamma homolog, snf4 contains a His151Gly
      substitution, and when this is introduced into gamma(1), AMP allosteric control
      is substantially lost and explains why the yeast snf1p/snf4p complex is
      insensitive to AMP. Arg70 in gamma(1) corresponds to the site of mutation in
      human gamma(2) and pig gamma(3) genes previously identified to cause an unusual
      cardiac phenotype and glycogen storage disease, respectively. Mutation of any of
      AMP binding site Arg residues to Gln substantially abolishes AMP allosteric
      control in expressed AMPK holoenzyme. The Arg/Gln mutations also suppress the
      previously described inhibitory properties of ATP and render the enzyme
      constitutively active. We propose that ATP acts as an intrasteric inhibitor by
      bridging the alpha and gamma subunits and that AMP functions to derepress AMPK
      activity.

PMID- 14691232
TI  - Two different proteins that compete for binding to thrombin have opposite kinetic
      and thermodynamic profiles.
AB  - Thrombin binds thrombomodulin (TM) at anion binding exosite 1, an allosteric site
      far from the thrombin active site. A monoclonal antibody (mAb) has been isolated
      that competes with TM for binding to thrombin. Complete binding kinetic and
      thermodynamic profiles for these two protein-protein interactions have been
      generated. Binding kinetics were measured by Biacore. Although both interactions
      have similar K(D)s, TM binding is rapid and reversible while binding of the mAb
      is slow and nearly irreversible. The enthalpic contribution to the DeltaG(bind)
      was measured by isothermal titration calorimetry and van't Hoff analysis. The
      contribution to the DeltaG(bind) from electrostatic steering was assessed from
      the dependence of the k(a) on ionic strength. Release of solvent H(2)O molecules
      from the interface was assessed by monitoring the decrease in amide solvent
      accessibility at the interface upon protein-protein binding. The mAb binding is
      enthalpy driven and has a slow k(d). TM binding appears to be entropy driven and
      has a fast k(a). The favorable entropy of the thrombin-TM interaction seems to be
      derived from electrostatic steering and a contribution from solvent release. The
      two interactions have remarkably different thermodynamic driving forces for
      competing reactions. The possibility that optimization of binding kinetics for a
      particular function may be reflected in different thermodynamic driving forces is
      discussed.

PMID- 14691233
TI  - Helix formation and the unfolded state of a 52-residue helical protein.
AB  - A growing class of proteins in biological processes has been found to be unfolded
      on isolation under normal solution conditions. We have used NMR spectroscopy to
      characterize the structural and dynamic properties of the unfolded and partially
      folded states of a 52-residue alanine-rich protein (Ala-14) at temperatures from 
      5 degrees C to 40 degrees C. At 40 degrees C, alanine residues in Ala-14 adopt
      phi and psi angles, consistent with a significant ensemble population of
      polyproline II conformation. Analysis of relaxation rates in the protein reveals
      that a series of residues, Gln 35-Ala 36-Ala 37-Lys 38-Asp 39-Asp 40-Ala 41-Ala
      42, displays slow motional dynamics at both -5 degrees C and 40 degrees C.
      Temperature-dependent chemical shift changes indicate that this region is the
      site of helix initiation. The remaining N-terminal residues become increasingly
      dynamic as they extend from the nucleation site. The C terminus remains dynamic
      and changes less with temperature, indicating it is relatively unstructured. Ala
      14 provides a high-resolution portrait of the unfolded state and the process of
      helix nucleation and propagation in the absence of tertiary contacts, information
      that bears on early events in protein folding.

PMID- 14691234
TI  - Are protein-protein interfaces more conserved in sequence than the rest of the
      protein surface?
AB  - Protein interfaces are thought to be distinguishable from the rest of the protein
      surface by their greater degree of residue conservation. We test the validity of
      this approach on an expanded set of 64 protein-protein interfaces using
      conservation scores derived from two multiple sequence alignment types, one of
      close homologs/orthologs and one of diverse homologs/paralogs. Overall, we find
      that the interface is slightly more conserved than the rest of the protein
      surface when using either alignment type, with alignments of diverse homologs
      showing marginally better discrimination. However, using a novel surface-patch
      definition, we find that the interface is rarely significantly more conserved
      than other surface patches when using either alignment type. When an interface is
      among the most conserved surface patches, it tends to be part of an enzyme active
      site. The most conserved surface patch overlaps with 39% (+/- 28%) and 36% (+/-
      28%) of the actual interface for diverse and close homologs, respectively.
      Contrary to results obtained from smaller data sets, this work indicates that
      residue conservation is rarely sufficient for complete and accurate prediction of
      protein interfaces. Finally, we find that obligate interfaces differ from
      transient interfaces in that the former have significantly fewer alignment gaps
      at the interface than the rest of the protein surface, as well as having buried
      interface residues that are more conserved than partially buried interface
      residues.

PMID- 14691235
TI  - Packing, specificity, and mutability at the binding interface between the p160
      coactivator and CREB-binding protein.
AB  - Among the most common interaction motifs between nuclear proteins is the
      recognition of one or more amphipathic helices. In an effort to determine
      principles behind this recognition, we have investigated the interaction between
      the p160 coactivator protein ACTR and the ACTR-binding domain of the CREB-binding
      protein, CBP. The two proteins use relatively small portions of their primary
      sequences to form a single synergistically folded domain consisting of six
      intertwined alpha-helices, three from each protein. Neither of the component
      polypeptides forms a cooperatively folded domain in isolation. However, a
      considerable amount of residual secondary structure remains in the isolated CBP
      domain according to CD spectroscopy. Chemical denaturation, differential scanning
      calorimetry, and ANS binding experiments demonstrate that the isolated CBP domain
      is not entirely unfolded but forms a helical state with the characteristics of a
      molten globule. Mutations probing the functional and energetic significance of a
      buried intermolecular Arg-Asp salt bridge in the interface of the protein complex
      suggest that these residues are tuned for functional discrimination and not
      strictly for binding affinity or stability. These results suggest a mechanism for
      formation of the complex where the unfolded ACTR domain interacts with the partly
      folded CBP domain in a rapid and specific manner to form the final stable
      complex.

PMID- 14691236
TI  - Refinement of homology-based protein structures by molecular dynamics simulation
      techniques.
AB  - The use of classical molecular dynamics simulations, performed in explicit water,
      for the refinement of structural models of proteins generated ab initio or based
      on homology has been investigated. The study involved a test set of 15 proteins
      that were previously used by Baker and coworkers to assess the efficiency of the
      ROSETTA method for ab initio protein structure prediction. For each protein, four
      models generated using the ROSETTA procedure were simulated for periods of
      between 5 and 400 nsec in explicit solvent, under identical conditions. In
      addition, the experimentally determined structure and the experimentally derived
      structure in which the side chains of all residues had been deleted and then
      regenerated using the WHATIF program were simulated and used as controls. A
      significant improvement in the deviation of the model structures from the
      experimentally determined structures was observed in several cases. In addition,
      it was found that in certain cases in which the experimental structure deviated
      rapidly from the initial structure in the simulations, indicating internal
      strain, the structures were more stable after regenerating the side-chain
      positions. Overall, the results indicate that molecular dynamics simulations on a
      tens to hundreds of nanoseconds time scale are useful for the refinement of
      homology or ab initio models of small to medium-size proteins.

PMID- 14691237
TI  - PFIT and PFRIT: bioinformatic algorithms for detecting glycosidase function from
      structure and sequence.
AB  - The identification of the enzymes involved in the metabolism of simple and
      complex carbohydrates presents one bioinformatic challenge in the post-genomic
      era. Here, we present the PFIT and PFRIT algorithms for identifying those
      proteins adopting the alpha/beta barrel fold that function as glycosidases. These
      algorithms are based on the observation that proteins adopting the alpha/beta
      barrel fold share positions in their tertiary structures having equivalent sets
      of atomic interactions. These are conserved tertiary interaction positions, which
      have been implicated in both structure and function. Glycosidases adopting the
      alpha/beta barrel fold share more conserved tertiary interactions than alpha/beta
      barrel proteins having other functions. The enrichment pattern of conserved
      tertiary interactions in the glycosidases is the information that PFIT and PFRIT
      use to predict whether any given alpha/beta barrel will function as a glycosidase
      or not. Using as a test set a database of 19 glycosidase and 45 nonglycosidase
      alpha/beta barrel proteins with low sequence similarity, PFIT and PFRIT can
      correctly predict glycosidase function for 84% of the proteins known to function
      as glycosidases. PFIT and PFRIT incorrectly predict glycosidase function for 25%
      of the nonglycosidases. The program PSI-BLAST can also correctly identify 84% of
      the 19 glycosidases, however, it incorrectly predicts glycosidase function for
      50% of the nonglycosidases (twofold greater than PFIT and PFRIT). Overall, we
      demonstrate that the structure-based PFIT and PFRIT algorithms are both more
      selective and sensitive for predicting glycosidase function than the sequence
      based PSI-BLAST algorithm.

PMID- 14691238
TI  - The N-terminal domain (IF2N) of bacterial translation initiation factor IF2 is
      connected to the conserved C-terminal domains by a flexible linker.
AB  - Bacterial translation initiation factor IF2 is a multidomain protein that is an
      essential component of a system for ensuring that protein synthesis begins at the
      correct codon within a messenger RNA. Full-length IF2 from Escherichia coli and
      seven fragments of the protein were expressed, purified, and characterized using
      nuclear magnetic resonance (NMR) and circular dichroism (CD) methods.
      Interestingly, resonances of the 6 kD IF2N domain located at the extreme N
      terminus of IF2 can be clearly identified within the NMR spectra of the full
      length 97-kD protein. (15)N NMR relaxation rate data indicate that (1) the IF2N
      domain is internally well ordered and tumbles in solution in a manner that is
      independent of the other domains of the IF2 protein, and (2) the IF2N domain is
      connected to the C-terminal regions of IF2 by a flexible linker. Chemical shifts
      of resonances within the isolated IF2N domain do not significantly differ from
      those of the corresponding residues within the context of the full-length 97-kD
      protein, indicating that IF2N is a structurally independent unit that does not
      strongly interact with other regions of IF2. CD and NMR data together provide
      evidence that Domains I-III of IF2 have unstructured and flexible regions as well
      as substantial helical content; CD data indicate that the helical content of
      these regions decreases significantly at temperatures above 35 degrees C. The
      features of structurally well-ordered N- and C-terminal domains connected by a
      flexible linker with significant helical content are reminiscent of another
      translation initiation factor, IF3.

PMID- 14691239
TI  - Prediction of the odorant binding site of olfactory receptor proteins by human
      mouse comparisons.
AB  - Olfactory receptors (ORs) are a large family of proteins involved in the
      recognition and discrimination of numerous odorants. These receptors belong to
      the G-protein coupled receptor (GPCR) hyperfamily, for which little structural
      data are available. In this study we predict the binding site residues of OR
      proteins by analyzing a set of 1441 OR protein sequences from mouse and human.
      The central insight utilized is that functional contact residues would be
      conserved among pairs of orthologous receptors, but considerably less conserved
      among paralogous pairs. Using judiciously selected subsets of 218 ortholog pairs
      and 518 paralog pairs, we have identified 22 sequence positions that are both
      highly conserved among the putative orthologs and variable among paralogs. These
      residues are disposed on transmembrane helices 2 to 7, and on the second
      extracellular loop of the receptor. Strikingly, although the prediction makes no
      assumption about the location of the binding site, these amino acid positions are
      clustered around a pocket in a structural homology model of ORs, mostly facing
      the inner lumen. We propose that the identified positions constitute the odorant
      binding site. This conclusion is supported by the observation that all but one of
      the predicted binding site residues correspond to ligand-contact positions in
      other rhodopsin-like GPCRs.

PMID- 14691240
TI  - Comparison of the 1.85 A structure of CYP154A1 from Streptomyces coelicolor A3(2)
      with the closely related CYP154C1 and CYPs from antibiotic biosynthetic pathways.
AB  - The genus Streptomyces produces two-thirds of microbially derived antibiotics.
      Polyketides form the largest and most diverse group of these natural products.
      Antibiotic diversity of polyketides is generated during their biosynthesis by
      several means, including postpolyketide modification performed by
      oxidoreductases, a broad group of enzymes including cytochrome P450
      monooxygenases (CYPs). CYPs catalyze site-specific oxidation of macrolide
      antibiotic precursors significantly affecting antibiotic activity. Efficient
      manipulation of Streptomyces CYPs in generating new antibiotics will require
      identification and/or engineering of monooxygenases with activities toward a
      diverse array of chemical substrates. To begin to link structure to function of
      CYPs involved in secondary metabolic pathways of industrially important species,
      we determined the X-ray structure of Streptomyces coelicolor A3(2) CYP154A1 at
      1.85 A and analyzed it in the context of the closely related CYP154C1 and more
      distant CYPs from polyketide synthase (EryF) and nonribosomal peptide synthetase
      (OxyB) biosynthetic pathways. In contrast to CYP154C1, CYP154A1 reveals an active
      site inaccessible from the molecular surface, and an absence of catalytic
      activities observed for CYP154C1. Systematic variations in the amino acid
      patterns and length of the surface HI loop correlate with degree of rotation of
      the F and G helices relative to the active site in CYP154A1-related CYPs,
      presumably regulating the degree of active site accessibility and its dimensions.
      Heme in CYP154A1 is in a 180 degrees flipped orientation compared with most other
      structurally determined CYPs.

PMID- 14691241
TI  - A new native EcHsp31 structure suggests a key role of structural flexibility for
      chaperone function.
AB  - Heat shock proteins and proteases play a crucial role in cell survival under
      conditions of environmental stress. The heat shock protein Hsp31, produced by
      gene hchA at elevated temperatures in Escherichia coli, is a homodimeric protein
      consisting of a large A domain and a smaller P domain connected by a linker. Two
      catalytic triads are present per dimer, with the Cys and His contributed by the A
      domain and an Asp by the P domain. A new crystal Form II confirms the dimer and
      catalytic triad arrangement seen in the earlier crystal Form I. In addition,
      several loops exhibit increased flexibility compared to the previous Hsp31 dimer
      structure. In particular, loops D2 and D3 are intriguing because their mobility
      leads to the exposure of a sizable hydrophobic patch made up by surface areas of
      both subunits near the dimer interface. The residues creating this hydrophobic
      surface are completely conserved in the Hsp31 family. At the same time, access to
      the catalytic triad is increased. These observations lead to the hypothesis for
      the functioning of Hsp31 wherein loops D2 and D3 play a key role: first, at
      elevated temperatures, by becoming mobile and uncovering a large hydrophobic area
      that helps in binding to client proteins, and second, by removing the client
      protein from the hydrophobic patch when the temperature decreases and the loops
      adopt their low-temperature positions at the Hsp31 surface. The proposed mode of
      action of flexible loops in the functioning of Hsp31 may be a general principle
      employed by other chaperones.

PMID- 14691242
TI  - FoldMiner: structural motif discovery using an improved superposition algorithm.
AB  - We report an unsupervised structural motif discovery algorithm, FoldMiner, which
      is able to detect global and local motifs in a database of proteins without the
      need for multiple structure or sequence alignments and without relying on prior
      classification of proteins into families. Motifs, which are discovered from
      pairwise superpositions of a query structure to a database of targets, are
      described probabilistically in terms of the conservation of each secondary
      structure element's position and are used to improve detection of distant
      structural relationships. During each iteration of the algorithm, the motif is
      defined from the current set of homologs and is used both to recruit additional
      homologous structures and to discard false positives. FoldMiner thus achieves
      high specificity and sensitivity by distinguishing between homologous and
      nonhomologous structures by the regions of the query to which they align. We find
      that when two proteins of the same fold are aligned, highly conserved secondary
      structure elements in one protein tend to align to highly conserved elements in
      the second protein, suggesting that FoldMiner consistently identifies the same
      motif in members of a fold. Structural alignments are performed by an improved
      superposition algorithm, LOCK 2, which detects distant structural relationships
      by placing increased emphasis on the alignment of secondary structure elements.
      LOCK 2 obeys several properties essential in automated analysis of protein
      structure: It is symmetric, its alignments of secondary structure elements are
      transitive, its alignments of residues display a high degree of transitivity, and
      its scoring system is empirically found to behave as a metric.

PMID- 14691243
TI  - HNH family subclassification leads to identification of commonality in the His-Me
      endonuclease superfamily.
AB  - The HNHc (SMART ID: SM00507) domain (SCOP nomenclature: HNH family) can be
      subclassified into at least eight subsets by iterative refinement of HMM
      profiles. An initial clustering of 323 proteins containing the HNHc domain helped
      identify the subsets. The subsets could be differentiated on the basis of the
      pattern of occurrence of seven defining features. Domain association is also
      different between the subsets. The subsets show organism as well as domain-based
      clustering, suggestive of propagation by both duplication and horizontal transfer
      events. Structure-based sequence analysis of the subsets led to the
      identification of common structural and sequence motifs in the HNH family with
      the other three families under the His-Me endonuclease superfamily.

PMID- 14691244
TI  - Active-site alkylation destabilizes human O6-alkylguanine DNA alkyltransferase.
AB  - O(6)-alkylguanine-DNA alkyltransferase (AGT) repairs pro-mutagenic O(6)
      alkylguanine and O(4)-alkylthymine lesions in DNA. The alkylated form of the
      protein is not reactivated; instead, it is rapidly ubiquitinated and degraded.
      Here, we show that alkylation destabilizes the native fold of the protein by 0.5
      1.2 kcal/mole and the DNA-binding function by 0.8-1.4 kcal/mole. On this basis,
      we propose that destabilization of the native conformational ensemble acts as a
      signal for ubiquitination.

PMID- 14691245
TI  - Energetics of ion conduction through the gramicidin channel.
AB  - The free energy governing K(+) conduction through gramicidin A channels is
      characterized by using over 0.1 micros of all-atom molecular dynamics simulations
      with explicit solvent and membrane. The results provide encouraging agreement
      with experiments and insights into the permeation mechanism. The free energy
      surface of K(+), as a function of both axial and radial coordinates, is
      calculated. Correcting for simulation artifacts due to periodicity and the lack
      of hydrocarbon polarizability, the calculated single-channel conductance for K(+)
      ions is 0.8 pS, closer to experiment than any previous calculation. In addition,
      the estimated single ion dissociation constants are within the range of
      experimental determinations. The relatively small free energy barrier to ion
      translocation arises from a balance of large opposing contributions from protein,
      single-file water, bulk electrolyte, and membrane. Mean force decomposition
      reveals a remarkable ability of the single-file water molecules to stabilize K(+)
      by -40 kcal/mol, roughly half the bulk solvation free energy. The importance of
      the single-file water confirms the conjecture of Mackay et al. [Mackay, D. H. J.,
      Berens, P. H., Wilson, K. R. & Hagler, A. T. (1984) Biophys. J. 46, 229-248]. Ion
      association with the channel involves gradual dehydration from approximately six
      to seven water molecules in the first shell, to just two inside the narrow pore.
      Ion permeation is influenced by the orientation of the single-file water column,
      which can present a barrier to conduction and give rise to long-range coupling of
      ions on either side of the pore. Small changes in the potential function,
      including contributions from electronic polarization, are likely to be sufficient
      to obtain quantitative agreement with experiments.

PMID- 14691246
TI  - Sequence determinants of amyloid fibril formation.
AB  - The establishment of rules that link sequence and amyloid feature is critical for
      our understanding of misfolding diseases. To this end, we have performed a
      saturation mutagenesis analysis on the de novo-designed amyloid peptide STVIIE
      (1). The positional scanning mutagenesis has revealed that there is a position
      dependence on mutation of amyloid fibril formation and that both very tolerant
      and restrictive positions to mutation can be found within an amyloid sequence. In
      this system, mutations that accelerate beta-sheet polymerization do not always
      lead to an increase of amyloid products. On the contrary, abundant fibrils are
      typically found for mutants that polymerize slowly. From these experiments, we
      have extracted a sequence pattern to identify amyloidogenic stretches in
      proteins. The pattern has been validated experimentally. In silico sequence
      scanning of amyloid proteins also supports the pattern. Analysis of protein
      databases has shown that highly amyloidogenic sequences matching the pattern are
      less frequent in proteins than innocuous amino acid combinations and that, if
      present, they are surrounded by amino acids that disrupt their aggregating
      capability (amyloid breakers). This study provides the potential for a proteome
      wide scanning to detect fibril-forming regions in proteins, from which molecules
      can be designed to prevent and/or disrupt this process.

PMID- 14691247
TI  - Structural, dynamic, and energetic aspects of long-range electron transfer in
      photosynthetic reaction centers.
AB  - Intramolecular electron transfer within proteins plays an essential role in
      biological energy transduction. Electron donor and acceptor cofactors are bound
      in the protein matrix at specific locations, and protein-cofactor interactions as
      well as protein conformational changes can markedly influence the electron
      transfer rates. To assess these effects, we have investigated charge
      recombination from the primary quinone acceptor to the special pair
      bacteriochlorophyll dimer in wild-type reaction centers of Rhodobacter
      sphaeroides and four mutants with widely modified free energy gaps. After light
      induced charge separation, the recombination kinetics were measured in the light-
      and dark-adapted forms of the protein from 10 to 300 K. The data were analyzed by
      using the spin-boson model, which allowed us to self-consistently determine the
      electronic coupling energy, the distribution of energy gaps, the spectral density
      of phonons, and the reorganization energy. The analysis revealed slow changes of
      the energy gap after charge separation. Interesting correlations of the control
      parameters governing electron transfer were found and related to structural and
      dynamic properties of the protein.

PMID- 14691248
TI  - Identification of many microRNAs that copurify with polyribosomes in mammalian
      neurons.
AB  - Localized translation in mammalian dendrites may play a role in synaptic
      plasticity and contribute to the molecular basis for learning and memory. The
      regulatory mechanisms that control localized translation in neurons are not well
      understood. We propose a role for microRNAs (miRNAs), a class of noncoding RNAs,
      as mediators of neuronal translational regulation. We have identified 86 miRNAs
      expressed in mammalian neurons, of which 40 have not previously been reported. A
      subset of these miRNAs exhibits temporally regulated expression in cortical
      cultures. Moreover, all of the miRNAs that were tested cofractionate with
      polyribosomes, the sites of active translation. These findings indicate that a
      large, diverse population of miRNAs may function to regulate translation in
      mammalian neurons.

PMID- 14691249
TI  - Genetic introgression as a potential to widen a species' niche: insights from
      alpine Carex curvula.
AB  - Understanding what causes the decreasing abundance of species at the margins of
      their distributions along environmental gradients has drawn considerable
      interest, especially because of the recent need to predict shifts in species
      distribution patterns in response to climatic changes. Here, we address the
      ecological range limit problem by focusing on the sedge, Carex curvula, a
      dominant plant of high-elevation grasslands in Europe, for which two ecologically
      differentiated but crosscompatible taxa have been described in the Alps. Our
      study heuristically combines an extensive phytoecological survey of alpine plant
      communities to set the niche attributes of each taxon and a population genetic
      study to assess the multilocus genotypes of 177 individuals sampled in typical
      and marginal habitats. We found that ecological variation strongly correlates
      with genetic differentiation. Our data strongly suggest that ecologically
      marginal populations of each taxon are mainly composed of individuals with
      genotypes resulting from introgressive hybridization. Conversely, no hybrids were
      found in typical habitats, even though the two taxa were close enough to
      crossbreed. Thus, our results indicate that genotype integrity is maintained in
      optimal habitats, whereas introgressed individuals are favored in marginal
      habitats. We conclude that gene flow between closely related taxa might be an
      important, although underestimated, mechanism shaping species distribution along
      gradients.

PMID- 14691251
TI  - Thyroid hormone controls the development of connections between the spinal cord
      and limbs during Xenopus laevis metamorphosis.
AB  - During premetamorphic stages, Xenopus laevis tadpoles expressing either a
      dominant-negative thyroid hormone (TH) receptor or a type-III iodothyronine
      deiodinase transgene in the nervous system have reduced TH-induced proliferation
      in the spinal cord and produce fewer hindlimb-innervating motorneurons. During
      prometamorphic stages, innervation of the hindlimbs is reduced, and few
      functional neuromuscular connections are formed. By metamorphic climax, limb
      movement is impaired, ranging from uncoordinated leg swimming to complete
      quadriplegia. This phenotype is due to transgene action in the tadpole spinal
      cord. The requirement of TH for neurogenesis during premetamorphosis is the
      earliest TH-regulated process reported to date in the sequence of metamorphic
      changes in anurans. The muscle formed during limb growth was previously shown to
      be a direct target of TH control. Here, we show that the same is true of the
      development of spinal cord cells that innervate the limbs.

PMID- 14691250
TI  - Epstein-Barr virus latent infection membrane protein 1 TRAF-binding site induces
      NIK/IKK alpha-dependent noncanonical NF-kappaB activation.
AB  - Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1)-induced NF
      kappaB activation is important for infected cell survival. LMP1 activates NF
      kappaB, in part, by engaging tumor necrosis factor (TNF) receptor-associated
      factors (TRAFs), which also mediate NF-kappaB activation from LTbetaR and CD40.
      LTbetaR and CD40 activation of p100/NF-kappaB2 is now known to be NIK/IKKalpha
      dependent and IKKbeta/IKKgamma independent. In the experiments described here, we
      found that EBV LMP1 induced p100/NF-kappaB2 processing in human lymphoblasts and
      HEK293 cells. LMP1-induced p100 processing was NIK/IKKalpha dependent and
      IKKbeta/IKKgamma independent. Furthermore, the LMP1 TRAF-binding site was
      required for p100 processing and p52 nuclear localization, whereas the LMP1 death
      domain-binding site was not. Moreover, the LMP1 TRAF-binding site preferentially
      caused RelB nuclear accumulation. In murine embryo fibroblasts (MEFs), IKKbeta
      was essential for LMP1 up-regulation of macrophage inflammatory protein (MIP)-2,
      TNFalpha, I-TAC, ELC, MIG, and CXCR4 RNAs. Interestingly, in IKKalpha knockout
      MEFs, LMP1 hyperinduced MIP-2, TNFalpha, and I-TAC expression, consistent with a
      role for IKKalpha in down-modulating canonical IKKbeta activation or its effects.
      In contrast, LMP1 failed to up-regulate CXCR4 and MIG RNA in IKKalpha knockout
      MEFs, indicating a dependence on noncanonical IKKalpha activation. Furthermore,
      LMP1 up-regulation of MIP-2 RNA in MEFs was both IKKbeta- and IKKgamma-dependent,
      whereas LMP1 upregulation of MIG and I-TAC RNA was fully IKKgamma independent.
      Thus, LMP1 induces typical canonical IKKbeta/IKKgamma-dependent, atypical
      canonical IKKbeta-dependent/IKKgamma-independent, and noncanonical NIK/IKKalpha
      dependent NF-kappaB activations; NIK/IKKalpha-dependent NF-kappaB activation is
      principally mediated by the LMP1 TRAF-binding site.

PMID- 14691252
TI  - Activation of Smad transcriptional activity by protein inhibitor of activated
      STAT3 (PIAS3).
AB  - Smad proteins play pivotal roles in mediating the transforming growth factor beta
      (TGF-beta) transcriptional responses. We show in this report that PIAS3, a member
      of the protein inhibitor of activated STAT (PIAS) family, activates TGF-beta/Smad
      transcriptional responses. PIAS3 interacts with Smad proteins, most strongly with
      Smad3. PIAS3 and Smad3 interact with each other at the endogenous protein level
      in mammalian cells and also in vitro, and the association occurs through the C
      terminal domain of Smad3. We further show that PIAS3 can interact with the
      general coactivators p300/CBP, the first evidence that a PIAS protein can
      associate with p300/CBP. In contrast, PIASy, which inhibits Smad transcriptional
      activity and other transcriptional responses, is unable to interact with
      p300/CBP. The RING domain of PIAS3 is essential for interaction with p300/CBP,
      and a RING domain mutant PIAS3, which cannot bind p300/CBP, no longer activates
      TGF-beta/Smad-dependent transcription. Furthermore, we show that PIAS3, Smad3,
      and p300 can form a ternary complex, which is markedly increased by TGF-beta
      treatment. Taken together, our studies indicate that on TGF-beta treatment, PIAS3
      can form a complex with Smads and p300/CBP and activate Smad transcriptional
      activity.

PMID- 14691253
TI  - 3D structure of the influenza virus polymerase complex: localization of subunit
      domains.
AB  - The 3D structure of the influenza virus polymerase complex was determined by
      electron microscopy and image processing of recombinant ribonucleoproteins
      (RNPs). The RNPs were generated by in vivo amplification using cDNAs of the three
      polymerase subunits, the nucleoprotein, and a model virus-associated RNA
      containing 248 nt. The polymerase structure obtained is very compact, with no
      apparent boundaries among subunits. The position of specific regions of the PB1,
      PB2, and PA subunits was determined by 3D reconstruction of either RNP-mAb
      complexes or tagged RNPs. This structural model is available for the polymerase
      of a negative-stranded RNA virus and provides a general delineation of the
      complex and its interaction with the template-associated nucleoprotein monomers
      in the RNP.

PMID- 14691255
TI  - A deoxyribozyme that harnesses light to repair thymine dimers in DNA.
AB  - In vitro selection was used to investigate whether nucleic acid enzymes are
      capable of catalyzing photochemical reactions. The reaction chosen was
      photoreactivation of thymine cyclobutane dimers in DNA by using serotonin as
      cofactor and light of wavelengths longer than the absorption spectrum of DNA.
      Curiously, the dominant single-stranded DNA sequence selected, UV1A, was found to
      repair its internal thymine dimer substrate efficiently even in the absence of
      serotonin or any other cofactor. UV1C, a 42-nucleotide fragment of UV1A, repaired
      the thymine dimer substrate in trans (k(cat)/k(uncat) = 2.5 x 10(4)), showing
      optimal activity with 305 nm light and thus resembling naturally occurring
      photolyase enzymes. Mechanistic investigation of UV1C indicated that its
      catalytic role likely exceeded the mere positioning of the substrate in a
      conformation favorable for photoreactivation. A higher-order structure, likely a
      quadruplex, formed by specific guanine bases within the deoxyribozyme, was
      implicated as serving as a light-harvesting antenna, with photoreactivation of
      the thymine dimer proceeding possibly via electron donation from an excited
      guanine base. In a primordial "RNA world," self-replicating nucleic acid
      populations may have been vulnerable to deactivation via UV light-mediated
      pyrimidine dimer formation. Photolyase nucleic acid enzymes such as the one
      described here could thus have played a role in preserving the integrity of such
      an RNA world.

PMID- 14691256
TI  - Could CO(2)-induced land-cover feedbacks alter near-shore upwelling regimes?
AB  - The response of marine and terrestrial environments to global changes in
      atmospheric carbon dioxide (CO(2)) concentrations will likely be governed by both
      responses to direct environmental forcing and responses to Earth-system feedbacks
      induced by that forcing. It has been proposed that anthropogenic greenhouse
      forcing will intensify coastal upwelling in eastern boundary current regions
      [Bakun, A. (1990) Science 247, 198-201]. Focusing on the California Current, we
      show that biophysical land-cover-atmosphere feedbacks induced by CO(2) radiative
      forcing enhance the radiative effects of CO(2) on land-sea thermal contrast,
      resulting in changes in eastern boundary current total seasonal upwelling and
      upwelling seasonality. Specifically, relative to CO(2) radiative forcing, land
      cover-atmosphere feedbacks lead to a stronger increase in peak- and late-season
      near-shore upwelling in the northern limb of the California Current and a
      stronger decrease in peak- and late-season near-shore upwelling in the southern
      limb. Such changes will impact both marine and terrestrial communities [Bakun, A.
      (1990) Science 247, 198-201; Soto, C. G. (2001) Rev. Fish Biol. Fish. 11, 181
      195; and Agostini, V. N. & Bakun, A. (2002) Fish. Oceanogr. 11, 129-142], and
      these and other Earth-system feedbacks should be expected to play a substantial
      role in shaping the response of eastern boundary current regions to CO(2)
      radiative forcing.

PMID- 14691254
TI  - Mutant human cells with constitutive activation of NF-kappaB.
AB  - We have used a genetic approach to generate eight different mutant human cell
      lines in which NF-kappaB is constitutively activated. These independent clones
      have different phenotypes and belong to several different genetic complementation
      groups. In one clone inhibitor of kappaB(IkappaB) kinase is constitutively
      active, but in the seven others it is not, despite the fact that IkappaB is
      degraded in all eight clones. Thus, IkappaB kinase-independent mechanisms of
      IkappaB degradation and NF-kappaB activation are predominant in these mutants.
      Biochemical analyses of the mutants revealed that they fall into at least five
      different categories, differing in the sets of upstream kinases that are
      activated, confirming multiple mechanisms of NF-kappaB activation. By introducing
      a retroviral cDNA library into the Ras C6 cell line, with constitutively active
      NF-kappaB, followed by selection for functional complementation, we isolated a
      cDNA encoding a C-terminal fragment of enolase 1 and identified it as negative
      regulator of NF-kappaB.

PMID- 14691257
TI  - U4 small nuclear RNA can function in both the major and minor spliceosomes.
AB  - U4 small nuclear RNA (snRNA) and U6 snRNA form a base-paired di-snRNP complex
      that is essential for pre-mRNA splicing of the major class of metazoan nuclear
      introns. The functionally analogous but highly diverged U4atac and U6atac snRNAs
      form a similar complex that is involved in splicing of the minor class of
      introns. Previous results with mutants of U6atac in which a substructure was
      replaced by the analogous structure from U6 snRNA suggested that wild-type U4
      snRNA might be able to interact productively with the mutant U6atac snRNA. Here
      we show that a mutant U4 snRNA designed to base pair with a mutant U6atac snRNA
      can activate U12-dependent splicing when coexpressed in an in vivo genetic
      suppression assay. This genetic interaction could also be demonstrated in an in
      vitro crosslinking assay. These results show that a U4/U6atac di-snRNP can
      correctly splice a U12-dependent intron and suggest that the specificity for
      spliceosome type resides in the U6 and U6atac small nuclear ribonucleoproteins.
      Further experiments suggest that expression of a mutant U4 snRNA that can bind to
      wild-type U6atac snRNA alters the specificity of some splice sites, providing an
      evolutionary rationale for maintaining two U4-like snRNAs.

PMID- 14691258
TI  - Heptahelical domain of metabotropic glutamate receptor 5 behaves like rhodopsin
      like receptors.
AB  - Although agonists bind directly in the heptahelical domain (HD) of most class-I
      rhodopsin-like G protein coupled receptors (GPCRs), class-III agonists bind in
      the extracellular domain of their receptors. Indeed, the latter possess a large
      extracellular domain composed of a cysteine-rich domain and a Venus flytrap
      module. Both the low sequence homology and the structural organization of class
      III GPCRs raised the question of whether or not the HD of these receptors
      functions the same way as rhodopsin-like GPCRs. Here, we show that the HD of
      metabotropic glutamate receptor 5 (mGlu(5)) displays the same agonist-independent
      constitutive activity as the wild-type receptor. Moreover, we show that the
      noncompetitive antagonist MPEP [2-methyl-6-(phenylethynyl)-pyridine
      hydrochloride] and the positive allosteric modulator DFB (3,3'
      difluorobenzaldazine) act as inverse agonist and full agonist, respectively, on
      the mGlu(5) HD in the absence of the extracellular domain. This finding
      illustrates that, like rhodopsin-like receptors, the HD of mGluRs can
      constitutively couple to G proteins and be negatively and positively regulated by
      ligands. These data show that the HD of mGluRs behave like any other class-I
      GPCRs in terms of G protein coupling and regulation by various types of ligands.

PMID- 14691260
TI  - Distinct forms of cholinergic modulation in parallel thalamic sensory pathways.
AB  - Mammalian thalamus is a critical site where early perception of sensorimotor
      signals is dynamically regulated by acetylcholine in a behavioral state-dependent
      manner. In this study, we examined how synaptic transmission is modulated by
      acetylcholine in auditory thalamus where sensory relay neurons form parallel
      lemniscal and nonlemniscal pathways. The former mediates tonotopic relay of
      acoustic signals, whereas the latter is involved in detecting and transmitting
      auditory cues of behavioral relevance. We report here that activation of
      cholinergic muscarinic receptors had opposite membrane effects on these parallel
      synaptic pathways. In lemniscal neurons, muscarine induced a sustained membrane
      depolarization and tonic firing by closing a linear K(+) conductance. In
      contrast, in nonlemniscal neurons, muscarine evoked a membrane hyperpolarization
      by opening a voltage-independent K(+) conductance. Depending on the level of
      membrane hyperpolarization and the strength of local synaptic input, nonlemniscal
      neurons were either suppressed or selectively engaged in detecting and
      transmitting synchronized synaptic input by firing a high-frequency spike burst.
      Immunohistochemical and Western blotting experiments showed that nonlemniscal
      neurons predominantly expressed M2 muscarinic receptors, whereas lemniscal cells
      had a significantly higher level of M1 receptors. Our data indicate that
      cholinergic modulation in the thalamus is pathway-specific. Enhanced cholinergic
      tone during behavioral arousal or attention may render synaptic transmission in
      nonlemniscal thalamus highly sensitive to the context of local synaptic
      activities.

PMID- 14691259
TI  - Chronic exposure to nitric oxide alters the free iron pool in endothelial cells:
      role of mitochondrial respiratory complexes and heat shock proteins.
AB  - The mechanisms of nitric oxide (NO) signaling include binding to the iron centers
      in soluble guanylate cyclase and cytochrome c oxidase and posttranslational
      modification of proteins by S-nitrosation. Low levels of NO control mitochondrial
      number in cells, but little is known of the impact of chronic exposure to high
      levels of NO on mitochondrial function in endothelial cells. The focus of this
      study is the interaction of NO with mitochondrial respiratory complexes in cell
      culture and the effect this has on iron homeostasis. We demonstrate that chronic
      exposure of endothelial cells to NO decreased activity and protein levels of
      complexes I, II, and IV, whereas citrate synthase and ATP synthase were
      unaffected. Inhibition of these respiratory complexes was accompanied by an
      increase in cellular S-nitrosothiol levels, modification of cysteines residues,
      and an increase in the labile iron pool. The NO-dependent increase in the free
      iron pool and inhibition of complex II was prevented by inhibition of
      mitochondrial protein synthesis, consistent with a major contribution of the
      organelle to iron homeostasis. In addition, inhibition of mitochondrial protein
      synthesis was associated with an increase in heat shock protein 60 levels, which
      may be an additional mechanism leading to preservation of complex II activity.

PMID- 14691261
TI  - Dynamic alterations in the conformation of the Ifng gene region during T helper
      cell differentiation.
AB  - Gene expression and silencing in eukaryotic systems can be controlled by
      regulatory elements acting over a distance. Here, we analyze chromatin
      conformation of the 24-kb region of the Ifng gene during CD4(+) T helper (Th)
      cell differentiation. We find that chromatin within this region is a highly
      flexible structure that undergoes dynamic changes during the course of
      transcriptional activation and silencing of the Ifng gene. Each Th subset
      displays a common core conformation in this gene region and unique features that
      distinguish neutral and effector Th1 and Th2 lineages. This chromatin
      configuration brings distal regions into close proximity to the gene. Th1 cells
      that produce high levels of IFN-gamma display the most open conformation. In
      contrast, IFN-gamma silent Th2 cells have a tightly closed conformation.
      Therefore, we postulate that there is a direct structure-function relationship
      between the spatial organization of the chromatin around the Ifng gene and its
      transcriptional potential.

PMID- 14691262
TI  - The genomic arrangement of T cell receptor variable genes is a determinant of the
      developmental rearrangement pattern.
AB  - Developmentally regulated V(D)J recombination profoundly influences immune
      repertoires, but the underlying mechanisms are poorly understood. In the
      endogenous T cell receptor Cgamma1 cluster, the 3' Vgamma3 gene (closest to
      Jgamma1) rearranges preferentially in the fetal period whereas rearrangement of
      the 5' Vgamma2 gene predominates in the adult. Reversing the positions of the
      Vgamma2 and Vgamma3 genes in a genomic transgene resulted in decreased
      rearrangement of the now 5' Vgamma3 gene in the fetal thymus and increased
      rearrangement of the now 3' Vgamma2 gene. The reversed rearrangement pattern was
      not accompanied by significant changes in chromatin accessibility of the
      relocated Vgamma genes. The results support a model in which the 3' location is
      the key determinant of rearrangement in the fetus, after which there is a
      promoter-dependent inactivation of Vgamma3 rearrangement in favor of Vgamma2
      rearrangement.

PMID- 14691263
TI  - Cell swelling, heat, and chemical agonists use distinct pathways for the
      activation of the cation channel TRPV4.
AB  - TRPV4 is a Ca(2+)- and Mg(2+)-permeable cation channel within the vanilloid
      receptor subgroup of the transient receptor potential (TRP) family, and it has
      been implicated in Ca(2+)-dependent signal transduction in several tissues,
      including brain and vascular endothelium. TRPV4-activating stimuli include
      osmotic cell swelling, heat, phorbol ester compounds, and 5',6'
      epoxyeicosatrienoic acid, a cytochrome p450 epoxygenase metabolite of arachidonic
      acid (AA). It is presently unknown how these distinct activators converge on
      opening of the channel. Here, we demonstrate that blockers of phospholipase A(2)
      (PLA(2)) and cytochrome p450 epoxygenase inhibit activation of TRPV4 by osmotic
      cell swelling but not by heat and 4alpha-phorbol 12,13-didecanoate. Mutating a
      tyrosine residue (Tyr-555) in the N-terminal part of the third transmembrane
      domain to an alanine strongly impairs activation of TRPV4 by 4alpha-phorbol 12,13
      didecanoate and heat but has no effect on activation by cell swelling or AA. We
      conclude that TRPV4-activating stimuli promote channel opening by means of
      distinct pathways. Cell swelling activates TRPV4 by means of the PLA(2)-dependent
      formation of AA, and its subsequent metabolization to 5',6'-epoxyeicosatrienoic
      acid by means of a cytochrome p450 epoxygenase-dependent pathway. Phorbol esters
      and heat operate by means of a distinct, PLA(2)- and cytochrome p450 epoxygenase
      independent pathway, which critically depends on an aromatic residue at the N
      terminus of the third transmembrane domain.

PMID- 14691265
TI  - Ethylene oxide and cancer.

PMID- 14691264
TI  - Role of serotonin in cocaine effects in mice with reduced dopamine transporter
      function.
AB  - The mesolimbic dopaminergic system, especially the nucleus accumbens, has
      received attention for its involvement in the reinforcing and addictive
      properties of cocaine and other drugs of abuse. It is generally accepted that the
      ability of cocaine to inhibit the dopamine transporter (DAT) is directly related
      to its reinforcing actions. However, mice with a genetic deletion of the DAT (DAT
      KO mice) still experience the rewarding effects of cocaine. These behavioral
      findings suggest that there is an alternate site for cocaine reinforcement. We
      demonstrate here that modulation of the serotonergic system in the ventral
      tegmental area, where the mesolimbic dopamine system originates, is a target of
      cocaine action. The ultimate effect of this serotonin mechanism in animal models
      with sustained elevations of dopamine may be a feed-forward enhancement of
      dopamine levels in the nucleus accumbens.

PMID- 14691266
TI  - Mortality analyses in a cohort of 18 235 ethylene oxide exposed workers: follow
      up extended from 1987 to 1998.
AB  - AIMS: To extend mortality follow up from 1987 to 1998 for cohort of 18 235 men
      and women exposed to ethylene oxide. METHODS: Standard mortality follow up, life
      table and Cox regression analysis. RESULTS: There were 2852 deaths, compared with
      1177 in the earlier 1987 follow up. There was no overall excess of haematopoietic
      cancers combined or of non-Hodgkin's lymphoma. However, internal exposure
      response analyses found positive trends for haematopoietic cancers which were
      limited to males (15 year lag). The trend in haematopoietic cancer was driven by
      lymphoid tumours (non-Hodgkin's lymphoma, myeloma, lymphocytic leukaemia), which
      also have a positive trend with cumulative exposure for males with a 15 year lag.
      Haematopoietic cancer trends were somewhat weaker in this analysis than trends in
      the earlier follow up, and analyses restricted to the post-1987 data did not show
      any significant positive trends (exposure levels dropped sharply in the early
      1980s). Breast cancer did not show any overall excess, although there was an
      excess in the highest cumulative exposure quartile using a 20 year lag. Internal
      exposure-response analyses found positive trend for breast cancer using the log
      of cumulative exposure with a 20 year lag. CONCLUSIONS: There was little evidence
      of any excess cancer mortality for the cohort as a whole, with the exception of
      bone cancer based on small numbers. Positive exposure-response trends for
      lymphoid tumours were found for males only. Reasons for the sex specificity of
      this effect are not known. There was also some evidence of a positive exposure
      response for breast cancer mortality.

PMID- 14691267
TI  - Risk of congenital anomalies in the vicinity of municipal solid waste
      incinerators.
AB  - BACKGROUND: Although municipal solid waste incineration (MSWI) has contributed to
      increase the overall environmental load of particulate matter containing dioxins
      and metals, evidence of health consequences to populations is sparse. AIMS: To
      assess at a regional level (in southeast France) the impact of these emissions on
      birth defect rates. METHODS: Communities with fewer than 50 000 inhabitants
      surrounding the 70 incinerators that operated at least one year from 1988 to 1997
      were studied. Each exposed community (n = 194) was assigned an exposure index
      estimated from a Gaussian plume model. Poisson models and a reference population
      of the 2678 unexposed communities in the region were used to calculate relative
      risks for congenital malformations, adjusted for year of birth, maternal age,
      department of birth, population density, average family income, and when
      available, local road traffic. RESULTS: The rate of congenital anomalies was not
      significantly higher in exposed compared with unexposed communities. Some
      subgroups of major anomalies, specifically facial clefts and renal dysplasia,
      were more frequent in the exposed communities. Among exposed communities, a dose
      response trend of risk with increasing exposure was observed for obstructive
      uropathies. Risks of cardiac anomalies, obstructive uropathies, and skin
      anomalies increased linearly with road traffic density. CONCLUSIONS: Although
      both incinerator emissions and road traffic may plausibly explain some of the
      excess risks observed, several alternative explanations, including exposure
      misclassification, ascertainment bias, and residual confounding cannot be
      excluded. Some of the effects observed, if real, might be attributable to old
      technology MSWIs and the persistent pollution they have generated.

PMID- 14691268
TI  - Occupational mortality in British commercial fishing, 1976-95.
AB  - AIMS: To establish the causes and circumstances of all deaths occurring at work
      or related to work among fishermen in British commercial fishing between 1976 and
      1995. METHODS: A retrospective study, based on official mortality files, with a
      population of 440 355 fishermen-years at risk. RESULTS: Of 616 deaths in British
      fishing, 454 (74%) were due to accidents at work, and 394 (87%) of these
      fishermen drowned. A total of 270 accidents were caused by casualties to vessels
      and 184 by personal accidents. There was no significant decline in the fatal
      accident rate, 103.1 per 100 000 fishermen-years, between 1976 and 1995. The
      fatal accident rate was 52.4 times higher (95% CI 42.9 to 63.8) than for all
      workers in Great Britain during the same period, and this relative risk increased
      through the 1980s up to 76.6 during 1991-95. Relative risks with the construction
      (12.3) and manufacturing (46.0) industries were higher than 5 and 20
      respectively, during 1959-68. Trawlers foundering in adverse weather was the most
      frequent cause of mortality from casualties to vessels (115 deaths), and 82 of
      145 personal accidents at sea arose during operations involving trawling nets.
      CONCLUSIONS: When compared with shore based industries, fishing remains at least
      as hazardous as before. Prevention should be aimed, most importantly, at the
      unnecessary operation of small vessels and trawling net manoeuvres in hazardous
      weather and sea conditions. Other measures should focus on preventing falls
      overboard, reducing fatigue, a more widespread use of personal flotation devices,
      and improvements in weather forecast evaluation.

PMID- 14691269
TI  - Working conditions, visual fatigue, and mental health among systems analysts in
      Sao Paulo, Brazil.
AB  - AIMS: To evaluate the association between working conditions and visual fatigue
      and mental health among systems analysts living in Sao Paulo, Brazil. METHODS: A
      cross sectional study was carried out by a multidisciplinary team. It included:
      ergonomic analysis of work, individual and group interviews, and 553 self applied
      questionnaires in two enterprises. The comparison population numbered 136 workers
      in different occupations. RESULTS: The study population mainly comprised young
      males. Among systems analysts, visual fatigue was associated with mental
      workload, inadequate equipment and workstation, low level of worker
      participation, being a woman, and subject's attitude of fascination by the
      computer. Nervousness and intellectual performance were associated with mental
      workload, inadequate equipment, work environment, and tools. Continuing education
      and leisure were protective factors. Work interfering in family life was
      associated with mental workload, difficulties with clients, strict deadlines,
      subject's attitude of fascination by the computer, and finding solutions of work
      problems outside work. Family support, satisfaction in life and work, and
      adequate work environment and tools were protective factors. Work interfering in
      personal life was associated with subject's attitude of fascination by the
      computer, strict deadlines, inadequate equipment, and high level of work
      participation. Satisfaction in life and work and continuing education were
      protective factors. The comparison population did not share common working
      factors with the systems analysts in the regression analysis. CONCLUSIONS: The
      main health effects of systems analysts' work were expressed by machine
      anthropomorphism, being very demanding, mental acceleration, mental absorption,
      and difficulty in dealing with emotions.

PMID- 14691270
TI  - Assessment of indoor air problems at work with a questionnaire.
AB  - AIMS: To assess the extent of indoor air problems in office environments in
      Finland. METHODS: Complaints and symptoms related to the indoor environment
      experienced by office workers were collected from 122 workplaces in 1996-99 by
      using the modified Indoor Air Questionnaire established by the Finnish Institute
      of Occupational Health. Altogether 11 154 employees took part in the survey.
      RESULTS: The most common problems were dry air (35% of the respondents), stuffy
      air (34%), dust or dirt in the indoor environment (25%), and draught (22%). The
      most common work related symptoms were irritated, stuffy, or runny nose (20%),
      itching, burning, or irritation of the eyes (17%), and fatigue (16%). Women
      reported indoor air problems and work related symptoms more often than men.
      Allergic persons and smokers reported indoor air problems more often, and
      experienced work related symptoms more often than non-allergic persons and non
      smokers. CONCLUSIONS: The complaints and work related symptoms associated with
      indoor air problems were common in office workers. The present questionnaire is a
      suitable tool for the occupational health personnel in investigating indoor air
      problems and the data of the survey can be used as a reference when the results
      of a survey at work are being analysed.

PMID- 14691271
TI  - Incidence of shoulder pain in repetitive work.
AB  - AIMS: To determine the predictiveness of personal and occupational factors for
      the onset of shoulder pain in occupations requiring repetitive work. METHODS: A
      sample of 598 workers in five activity sectors completed a self administered
      questionnaire in 1993-94 and again three years later. Both questionnaires
      included questions about shoulder pain. The associations between various factors
      at baseline and subsequent shoulder pain were studied among subjects free from
      shoulder pain at baseline. RESULTS: The incidence of shoulder pain was associated
      with several independent risk factors: depressive symptoms, low level of job
      control, and biomechanical constraints. After adjustment for other risk factors,
      the presence of depressive symptoms predicted occurrence of shoulder pain. A low
      level of job control was also associated with the onset of shoulder pain in both
      sexes. For men, repetitive use of a tool was a strong predictor, while the two
      most important biomechanical risk factors for women were use of vibrating tools
      and working with arms above shoulder level. CONCLUSION: This study used a
      longitudinal approach to examine different sets of risk factors for shoulder pain
      simultaneously. The results confirm the role of several biomechanical
      constraints. Psychological symptoms and a low level of job control also play a
      role.

PMID- 14691272
TI  - Work factors as predictors of sickness absence attributed to airway infections; a
      three month prospective study of nurses' aides.
AB  - AIMS: To identify the work factors that are related to sickness absence
      attributed to airway infections (AAI) in nurses' aides. METHODS: The sample
      comprised 5563 Norwegian nurses' aides, not on sick leave when they completed a
      mailed questionnaire in 1999. Of these, 4931 (88.6%) completed a second
      questionnaire three months later. The outcome measure was the three month
      incidence proportion of certified AAI (>3 days), assessed by self reports at
      follow up. RESULTS: Working in a paediatric ward (odds ratio (OR) 2.42; 95%
      confidence interval (CI) 1.39 to 4.21), perceived lack of encouraging and
      supportive culture in the work unit (OR 1.78; 95% CI 1.21 to 2.61), and reporting
      medium (OR 1.52; 95% CI 1.09 to 2.12), and high levels (OR 1.60; 95% CI 1.13 to
      2.26) of role conflicts at work were associated with an increased risk of AAI,
      after adjustments for baseline health complaints, demographic and familial
      factors, smoking, and a series of physical, psychological, and organisational
      work factors. The individual level factors male gender, smoking 10 cigarettes per
      day or more, having widespread pain, having had an accident related neck injury,
      and having long term health problems also predicted AAI. CONCLUSIONS: In nurses'
      aides, sickness absence attributed to airway infections seems to be related to
      the type of ward in which the aides are working, and to psychological and social
      work factors. Declaring airway infections as occupational diseases would have
      important consequences for the social security system.

PMID- 14691273
TI  - Gender differences in the occurrence of farm related injuries.
AB  - AIMS: To use national surveillance data in Canada to describe gender differences
      in the pattern of farm fatalities and severe injuries (those requiring
      hospitalisation). METHODS: Data from the Canadian Agricultural Injury
      Surveillance Program (CAISP) included farm work related fatalities from 1990 to
      1996 for all Canadian provinces and abstracted information from hospital
      discharge records from eight provinces for the five fiscal years of 1990 to 1994.
      Gender differences in fatalities and injuries were examined by comparison of
      proportions and stratified by sex, injury class (machinery, non-machinery), and
      age group. RESULTS: Over the six year period of 1990 to 1996 there were
      approximately 11 times as many agriculture related fatalities for males compared
      to females (655 and 61, respectively). The most common machinery mechanisms of
      fatal injuries were roll-over (32%) for males and run-over (45%) for females.
      Agricultural machinery injuries requiring hospitalisation showed similar
      patterns, with proportionally more males over age 60 injured. The male:female
      ratio for non-machinery hospitalisations averaged 3:1. A greater percentage of
      males were struck by or caught against an object, whereas for females, animal
      related injuries predominated. CONCLUSIONS: Gender is an important factor to
      consider in the interpretation of fatal and non-fatal farm injuries. A greater
      number of males were injured, regardless of how the occurrence of injury was
      categorised, particularly when farm machinery was involved. As women increasingly
      participate in all aspects of agricultural production, there is a need to
      collect, interpret, and disseminate information on agricultural injury that is
      relevant for both sexes.

PMID- 14691274
TI  - Mortality among a cohort of uranium mill workers: an update.
AB  - AIMS: To evaluate the mortality experience of 1484 men employed in seven uranium
      mills in the Colorado Plateau for at least one year on or after 1 January 1940.
      METHODS: Vital status was updated through 1998, and life table analyses were
      conducted. RESULTS: Mortality from all causes and all cancers was less than
      expected based on US mortality rates. A statistically significant increase in non
      malignant respiratory disease mortality and non-significant increases in
      mortality from lymphatic and haematopoietic malignancies other than leukaemia,
      lung cancer, and chronic renal disease were observed. The excess in lymphatic and
      haematopoietic cancer mortality was due to an increase in mortality from
      lymphosarcoma and reticulosarcoma and Hodgkin's disease. Within the category of
      non-malignant respiratory disease, mortality from emphysema and pneumoconioses
      and other respiratory disease was increased. Mortality from lung cancer and
      emphysema was higher among workers hired prior to 1955 when exposures to uranium,
      silica, and vanadium were presumably higher. Mortality from these causes of death
      did not increase with employment duration. CONCLUSIONS: Although the observed
      excesses were consistent with our a priori hypotheses, positive trends with
      employment duration were not observed. Limitations included the small cohort size
      and limited power to detect a moderately increased risk for some outcomes of
      interest, the inability to estimate individual exposures, and the lack of smoking
      data. Because of these limitations, firm conclusions about the relation of the
      observed excesses in mortality and mill exposures are not possible.

PMID- 14691275
TI  - Assessing spatial fluctuations, temporal variability, and measurement error in
      estimated levels of disinfection by-products in tap water: implications for
      exposure assessment.
AB  - AIMS: To assess spatial fluctuations, temporal variability, and errors due to
      sampling and analysis in levels of disinfection by-products in routine monitoring
      tap water samples and in water samples collected in households within the same
      distribution system for an exposure assessment study. METHODS: Mixed effects
      models were applied to quantify seasonal effects and the degree to which
      trihalomethane (THM) levels vary among households or locations relative to
      variation over time within seasons for any given location. In a separate
      analysis, the proportion of total variation due to measurement error arising from
      sampling and analysis was also quantified. RESULTS: THM levels were higher in the
      summer relative to other seasons. Differences in the relative magnitude of the
      intra- and inter-household components of variation were observed between the two
      sets of THM measurements, with a greater proportion of the variation due to
      differences within seasons for the routine monitoring data and a greater
      proportion of the variation due to differences across locations for the exposure
      assessment study data. Such differences likely arose due to differences in the
      strategies used to select sites for sampling and in the time periods over which
      the data were collected. With the exception of bromodichloromethane, measurement
      errors due to sampling and analysis contributed a small proportion of the total
      variation in THM levels. CONCLUSIONS: The utility of routine monitoring data in
      assigning exposure in epidemiological studies is limited because such data may
      not represent the magnitude of spatial variability in levels of disinfection by
      products across the distribution system. Measurement error contributes a
      relatively small proportion to the total variation in THM levels, which suggests
      that gathering a greater number of samples over time with fewer replicates
      collected at each sampling location is more efficient and would likely yield
      improved estimates of household exposure.

PMID- 14691276
TI  - Dimethyl sulphate; a hidden problem in occupational medicine.
AB  - BACKGROUND: In a chemical plant, alkylating agents (mainly ethylene oxide and
      propylene oxide, but also dimethyl sulphate) are utilised for the production of
      special surfactants. AIMS: To determine possible uptakes of dimethyl sulphate by
      workers using N-methylvaline. METHODS: Sixty two workers in a chemical plant (38
      smokers, 24 non-smokers) with potential exposure to dimethyl sulphate were
      monitored with respect to their blood levels of N-methylvaline. Ten laboratory
      workers without exposure to methylating agents were controls. Blood samples of
      eight workers from a specific working area were analysed for N-methylvaline in a
      follow up investigation four months later. RESULTS: The 95th centile for N
      methylvaline was 80.7 microg/l blood in the exposed workers compared to 12.4
      microg/l blood in controls. In a hot spot area, 10 workers exceeded the German
      exposure equivalent value for dimethyl sulphate (40 microg/l blood) up to
      fourfold. In contrast, dimethyl sulphate has not been detectable in workplace air
      in this area. In a follow up investigation of eight of these 10 workers, N
      methylvaline levels were significantly lower, but still increased. CONCLUSIONS:
      The present study is to our knowledge the first to report increased N
      methylvaline levels after occupational exposure to dimethyl sulphate. As ambient
      monitoring values in the plant could not explain this exposure, skin contact was
      considered to be the main route of uptake for this substance. Dimethyl sulphate
      may therefore represent an occupational problem that has been generally
      underestimated in the past.

PMID- 14691277
TI  - Is colour vision impairment associated with cognitive impairment in solvent
      exposed workers?
AB  - AIMS: To determine whether acquired colour vision deficits in solvent exposed
      individuals are associated with cognitive impairment. METHODS: A sample of 82
      painters and 38 other subjects were studied. Alcohol, drug, and smoking histories
      were obtained. Colour vision was tested using the Lanthony D-15-d colour vision
      test. Cognitive impairment was measured using the Benton visual retention test,
      Trail making A, and Trail making B tests. Pre-morbid IQ was estimated using the
      National Adult Reading Test. Solvent exposure in all subjects was estimated using
      a previously validated, structured subjective assessment methodology. RESULTS:
      After exclusion of subjects with competing causes of colour vision impairment the
      final group of men numbered 78. There was a significant association on multiple
      linear regression between the mean colour confusion index (CCI) and three
      measures of cognitive impairment, the Benton visual retention test, Trail making
      A, and Trail making B tests after adjusting for the effects of age (or IQ as
      appropriate), alcohol, and smoking. CONCLUSION: Acquired colour vision loss is
      associated with cognitive impairment in solvent exposed workers. However, given
      the prevalence of acquired colour vision losses in the adult population, colour
      vision testing is unlikely to be of value as a screening test.

PMID- 14691278
TI  - Work status after workers' compensation claims for upper limb musculoskeletal
      disorders.
AB  - AIM: To provide information on employment status after workers' compensation (WC)
      claims for musculoskeletal disorders of the limbs (MSDs). METHODS: Two-year
      follow up of the workers who filed a WC claim for MSDs in 1996 in the Pays de la
      Loire region. Of the 701 eligible workers, 514 workers (70%) participated.
      Information was requested by means of a mailed questionnaire about the
      characteristics of the MSDs and job status at the time of the WC claim and two
      years later. RESULTS: Two years after the WC claim, 65% of the claimants had
      returned to work in the same company, often without any ergonomic improvement,
      12% had retired or had left employment voluntarily, and 18% had been dismissed.
      The risk of dismissal was associated with three factors: being older than 45
      years, having two or more MSDs at claim, and working in the cleaning services
      sector.

PMID- 14691279
TI  - Total body iron overload in welder's siderosis.
AB  - Welder's siderosis occurs as a consequence of the inhalation of iron dust. The
      iron overload of welder's siderosis is usually considered to be confined to the
      lungs. Here we present three proven cases of welder's siderosis associated with
      evidence of increased total systemic iron stores, as evidenced by increased serum
      ferritin levels. Multiple investigations including molecular genotyping for the
      common mutations found in genetic haemochromatosis failed to prove this was due
      to haemochromatosis, nor was there any evidence of any other recognised cause of
      systemic iron overload. Thus the systemic iron overload described seems likely to
      be due to either occupational exposure, an uncharacterised genetic
      haemochromatosis, or a combination of both.

PMID- 14691280
TI  - Risk of fatal industrial accidents and death from other external causes among
      asphalt workers.
AB  - The hypothesis that asphalt workers are at increased risk of mortality from
      industrial accidents and other external causes was tested. Mortality rates for
      external and violent causes of death in a cohort of asphalt industry employees
      from seven European countries and Israel were compared to that of the general
      population. There was no evidence that mortality from external causes was
      increased among long term employees in asphalt application and mixing. There was
      an increased risk for mortality due to external causes among short term workers.
      However, none of the fatal accidents among short term workers appear to have
      occurred during employment in the studied asphalt companies. Overall, no evidence
      was found supporting the hypothesis that asphalt workers are at increased risk of
      fatal industrial or road accidents. Mortality from other external causes did not
      increase in this population as a whole, but increased risks among short term
      workers deserve further attention.

PMID- 14691281
TI  - World at work: bricklayers and bricklayers' assistants.

PMID- 14691282
TI  - Severe acute respiratory syndrome (SARS).

PMID- 14691283
TI  - Psychosocial factors at work in relation to low back pain and consequences of low
      back pain; a systematic, critical review of prospective cohort studies.
AB  - Relevant studies of low back pain (LBP) published between 1990 and 2002 were
      systematically retrieved via electronic databases and checking of reference
      lists. Forty papers fulfilled the inclusion criteria; 10 were of high quality. A
      wide variety of instruments had been used for collection of data on work related
      psychosocial factors, many of which had not undergone any form of validation.
      Moderate evidence was found for no association between LBP and perception of
      work, organisational aspects of work, and social support at work. There was
      insufficient evidence for a positive association between stress at work and LBP.
      No conclusions could be drawn regarding perception of work and consequences of
      LBP. There was strong evidence for no association between organisational aspects
      of work and moderate evidence for no association between social support at work
      and stress at work and consequences of LBP.

PMID- 14691284
TI  - Microbiological evolution of hay and relapse in patients with farmer's lung.
AB  - BACKGROUND: Recent studies in France have shown that Absidia corymbifera and, to
      a lesser degree Eurotium amstelodami and Wallemia sebi, play a role in farmer's
      lung disease (FLD), but that Saccharopolyspora rectivirgula, classically
      incriminated, does not. Little is known about farmers' reactions to these fungi
      or the circumstances which lead to exposure. AIMS: To investigate the conditions
      which favour the development of these microorganisms in hay and to analyse the
      relation between their concentration and the risk of occurrence of FLD. METHODS:
      Sequential microbiological analyses of each batch of hay stored in 10 farms at
      risk for FLD and a serological survey of 10 farmers (five with a past history of
      FLD). RESULTS: Exposure to microorganisms varied widely according to farms and
      periods. These microorganisms usually reached a peak in January and proliferated
      when harvesting conditions favoured excessive humidity in hay (rain during
      harvest, soil in the hay). Three of the five FLD patients presented with FLD
      respiratory recurrence and positive serology for A corymbifera during the winter
      (2000-01), after exposure to a significantly higher amount of A corymbifera than
      other farmers. Similar, but less significant, results were found for E
      amstelodami exposure, but not with W sebi. CONCLUSIONS: Results contribute to
      confirming A corymbifera as a major aetiological agent of FLD in Doubs, and
      encourage further studies with a view to implementing preventive measures.

PMID- 14691285
TI  - Muscular strength and vibration thresholds during two years after acute poisoning
      with organophosphate insecticides.
AB  - AIMS: To evaluate the association of acute organophosphate (OP) poisoning with
      chronic sensory and motor neurological impairment. METHODS: This study concerns
      the third of a series of three examinations of hand strength and vibration
      thresholds in a two year period after acute OP poisoning among 48 Nicaraguan men.
      The first two examinations were performed at hospital discharge and seven weeks
      after poisoning, and the present examination two years later. Twenty eight cattle
      ranchers and fishermen who had never experienced pesticide poisoning were
      examined as controls, also three times over the two year period. The poisonings
      were categorised as caused by "non-neuropathic" OPs and "neuropathic" OPs, each
      subdivided in moderate and severe poisonings. RESULTS: Men poisoned with OP
      insecticides had persistent reduced hand strength. We previously reported
      weakness at hospital discharge for OP poisoned in all categories that worsened
      seven weeks later for those severely poisoned with neuropathic OPs. Strength
      improved over time, but the poisoned were still weaker than controls two years
      after the poisoning, most noticeably among the subjects most severely poisoned
      with neuropathic OPs. Also, index finger and toe vibration thresholds were
      slightly increased at the end of the two year period, among men with OP
      poisonings in all categories, but patterns of onset and evolvement of impairment
      of vibration sensitivity were less clear than with grip and pinch strength.
      CONCLUSIONS: Persistent, mainly motor, impairment of the peripheral nervous
      system was found in men two years after OP poisoning, in particular in severe
      occupational and intentional poisonings with neuropathic OPs. This finding is
      possibly due to remaining organophosphate induced delayed polyneuropathy.

PMID- 14691287
TI  - Normal and pathologic soft tissue remodeling: role of the myofibroblast, with
      special emphasis on liver and kidney fibrosis.

PMID- 14691288
TI  - Androgen receptor mutations in high-grade prostate cancer before hormonal
      therapy.
AB  - Androgen action is mediated through androgen receptor (AR), which appears to
      undergo structural and functional alterations during prostate cancer (CaP)
      progression. AR mutations have been infrequently reported in CaP before hormonal
      therapy, but in untreated, advanced tumors AR mutations are suggested to be more
      common. To investigate the frequency of AR mutations in aggressive CaP before
      hormonal therapy, we have analyzed AR coding region for aberrations in 21
      paraffin-embedded prostate carcinoma samples (14 primary tumors, 7 metastases) of
      poor histologic differentiation. Single-stranded conformational polymorphism and
      sequencing analyses revealed AR missense mutations in 29% (4/14) of the primary
      tumors and in one (14%) metastasis. Mutations resided in the transactivation
      domain and in the hinge region. One of the hinge region mutants, Ser646Phe, that
      was identified in a patient with short endocrine therapy response, exhibited a
      markedly increased transcriptional activity on single androgen response element
      containing promoters. In conclusion, AR mutations are frequent in high-grade CaP
      before initiation of hormonal therapy, and these mutations may play a role in
      poor therapy response and emergence of hormone-refractory CaP in some cases.

PMID- 14691289
TI  - Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist,
      attenuates myocardial ischemia/reperfusion injury in a rat model.
AB  - Thiazolidinediones are insulin-sensitizing drugs, ligands for peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma), which play an important role
      in the modulation of inflammatory responses. Myocardial ischemia/reperfusion
      (MI/R) injury is associated with inflammation, in which various cells,
      particularly monocytes and macrophages, are involved. This study examined the
      effects of the thiazolidinedione peroxisome proliferator-activated receptor-gamma
      ligand, pioglitazone, in a rat model of MI/R injury. Pioglitazone at 3 mg/kg/day
      or the vehicle was administered for 7 days before rats were subjected to 30
      minutes of coronary ligation followed by 24 hours of reperfusion. The mRNA
      expression [monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion
      molecule-1] in the ischemic region, the number of infiltrating macrophages in the
      ischemic region, and the myocardial infarct size were examined. The inhibitory
      effects of pioglitazone on activated macrophages were studied in vitro. Phorbol
      12-myristate 13-acetate-induced MCP-1 production, in the absence or presence of
      pioglitazone, were assayed in cultured macrophages. Compared with the control
      group, (1). mRNA levels of MCP-1 and intercellular adhesion molecule-1 and the
      number of infiltrating macrophages in the ischemic region were significantly
      lower in the pioglitazone-treated group; and (2). myocardial infarct size was
      significantly smaller in the pioglitazone-treated group. Phorbol 12-myristate 13
      acetate-stimulated cultured macrophages in the presence of pioglitazone produced
      significantly lower levels of MCP-1 than the stimulated control in the absence of
      pioglitazone. These observations demonstrate that pioglitazone has anti
      inflammatory effects in MI/R injury that are independent of its insulin
      sensitizing effect.

PMID- 14691290
TI  - Attenuated cerulein-induced pancreatitis in nuclear factor-kappaB-deficient mice.
AB  - Nuclear factor (NF)-kappaB plays a central role in acute pancreatitis. We studied
      cerulein (CER)-induced pancreatitis in NF-kappaB knockout (KO) mice. NF-kappaB KO
      mice and normal control littermate wild-type (WT) mice were given four
      hyperstimulating doses of cerulein every hour to elicit secreatagogue-induced
      pancreatitis. Malonildialdehyde activity, glutathione levels, myeloperoxidase
      activity, TNF-alpha, and NF-kappaB binding activity and its inhibitory protein
      IkappaBalpha were studied in the pancreas. Furthermore, we measured plasma lipase
      and amylase and the histological damage. KO mice had reduced malonildialdehyde
      levels (WT + CER = 4.083 +/- 0.95 micromol/g; KO + CER = 1.513 +/- 0.63
      microol/g), decreased myeloperoxidase activity (WT + CER = 19.3 +/- 2.39 mU/g; KO
      + CER = 10.21 +/- 2.05 mU/g), increased glutathione levels (WT + CER 6.22 +/-
      2.46 micromol/g; KO + CER = 15. 516 +/- 2.92 micromol/g), and reduced serum
      levels of amylase (WT + CER = 2519 +/- 656.9 U/L; KO + CER = 916 +/- 280.4 U/L)
      and lipase (WT + CER = 1420 +/- 170 U/L; KO + CER = 861 +/- 172. 3 U/L). KO mice
      showed reduced pancreatic NF-kappaB activation, decreased TNF-alpha tissue
      content, and reduced histologic alterations. Our data suggest that KO mice have
      an attenuated cerulein-induced pancreatitis and help to define the possible
      interaction between NF-kappaB activation and oxidative stress in this deleterious
      event.

PMID- 14691291
TI  - Differences in the involvement of prostanoids from Kupffer cells in the mediation
      of anaphylatoxin C5a-, zymosan-, and lipopolysaccharide-dependent hepatic glucose
      output and flow reduction.
AB  - Various inflammatory stimuli such as anaphylatoxin C5a, zymosan, and
      lipopolysaccharides (LPSs) have been reported both to enhance glucose output in
      the perfused rat liver and to induce prostanoid (ie, prostaglandin and
      thromboxane) release from Kupffer cells, the resident liver macrophages. Because
      prostanoids can enhance glucose output from hepatocytes, it was the aim of this
      study to compare the possible roles of prostanoids released after C5a, zymosan,
      and LPS in the mediation of hepatic glucose output. In perfused livers both C5a
      and zymosan immediately enhanced glucose output, reduced flow, and induced
      prostanoid overflow into the hepatic vein, but with different quantities and
      kinetics. Only the C5a-induced but not the zymosan-induced effects were abrogated
      by inhibitors of prostanoid signaling as the prostanoid synthesis inhibitor
      indomethacin and the thromboxane receptor antagonist daltroban. In contrast to
      C5a and zymosan, LPS had no effect on glucose output, flow rate, or prostanoid
      overflow. In isolated Kupffer cells, C5a and zymosan induced maximal release of
      prostaglandins D(2) and E(2) and of thromboxane A(2) within a period of 0 to 2
      minutes and 5 to 15 minutes, respectively. In pulse-chase experiments, maximal
      prostanoid release was already observed after 2 minutes of continuous stimulation
      with C5a, but only after 10 to 15 minutes of continuous stimulation with zymosan.
      LPS-dependent prostanoid release was not seen before 1 hour. Thus, even though
      C5a, zymosan, and LPS induced prostanoid release from Kupffer cells, only C5a
      quickly regulated hepatic glucose metabolism in a prostanoid-dependent manner
      (due to the kinetics and quantities of prostanoids released).

PMID- 14691292
TI  - TNF-independent development of transient anemia of chronic disease in a mouse
      model of protracted septic peritonitis.
AB  - TNF is considered one of the inflammatory cytokines and contributes mainly to the
      generation of anemia of chronic disease (ACD). In nude mice TNF has been reported
      to impair iron metabolism and erythropoiesis, leading to anemia with a low serum
      iron and preserved iron stores. In this work, we established a murine model for
      ACD based on sublethal cecal ligation and puncture (CLP) with ensuing protracted
      peritonitis. Starting on Day 3 after CLP, a severe protracted depression of
      erythropoiesis in the bone marrow was noted. Two weeks after CLP, we observed a
      moderate normochromic anemia, low serum iron concentration, and preserved iron
      stores consistent with transient ACD. To determine whether TNF contributes to the
      development of ACD in vivo, we neutralized TNF after CLP shortly before and
      during the phase of most severe bone marrow depression to prevent anemia.
      Additionally, we studied TNF-deficient mice undergoing CLP. Two weeks after CLP,
      we determined red blood count, hemoglobin concentration, hematocrit, serum iron
      concentration, and iron stores in spleens of wild-type mice, TNF-deficient mice,
      and mice after neutralization of TNF. Neutralization of TNF after CLP could not
      prevent mice from contracting anemia. Accordingly, TNF-deficient mice developed
      anemia to the same extent as wild-type mice. Serum iron concentration was lowered
      and iron stores were overloaded in both TNF-deficient and wild-type mice after
      CLP. Our results clearly demonstrate that TNF is not a mediator of ACD in our
      model with transient anemia induced by protracted septic peritonitis.

PMID- 14691293
TI  - A novel tool for detecting amyloid deposits in systemic amyloidosis in vitro and
      in vivo.
AB  - We synthesized (trans,trans)-1-bromo-2,5-bis-(3-hydroxycarbonyl-4
      hydroxy)styrylbenzene (BSB) and used this compound to detect amyloid fibrils in
      autopsy and biopsy samples from patients with localized amyloidosis, such as
      familial prion disease, and systemic amyloidosis, such as familial amyloidotic
      polyneuropathy, amyloid A (AA) amyloidosis, light chain (AL) amyloidosis, and
      dialysis-related amyloidosis. BSB showed reactions in all Congo red-positive and
      immunoreactive regions of the samples examined in the study, and some amyloid
      fibrils in the tissues could be detected more precisely with BSB than with the
      other methods. In the mouse model of AA amyloidosis, injected BSB reacted with
      amyloid in all regions in the serial sections in which Congo red staining was
      positive. A highly sensitive 27-MHz quartz crystal microbalance analysis revealed
      that BSB showed a significant affinity for amyloid fibrils purified from familial
      amyloidotic polyneuropathy and dialysis-related amyloidosis samples and
      suppressed formation of transthyretin amyloid in vitro. These results suggest
      that BSB may become a valuable tool for detection of amyloid deposits in
      amyloidosis and of the mechanism of amyloid formation.

PMID- 14691294
TI  - Specific MAP-kinase blockade protects against renal damage in homozygous
      TGR(mRen2)27 rats.
AB  - Angiotensin II (AngII) plays an important role in renal damage by acting on
      hemodynamics, cell-growth, proliferation, and fibrosis, mainly by effects on the
      AngII type 1 (AT(1)) receptor. The AT(1) receptor activates several intracellular
      signaling molecules such as mitogen-activated protein kinases extracellular
      signal-regulated kinase (ERK) and p38, but their role in AngII-mediated renal
      damage is not well characterized. We therefore investigated whether pharmacologic
      blockade of ERK and p38 could prevent renal damage in high-renin homozygous
      transgenic rats (Ren2), with the effects of an AT(1) receptor antagonist (AT(1)
      RA) as a reference. Seven-week-old homozygous Ren2 rats were treated with low
      dose AT(1)-RA candesartan, ERK inhibitor tyrphostin, or p38 inhibitor SB239063
      for 4 weeks. Untreated Ren2 and SD rats served as controls. Blood pressure was
      measured at 7 and 11 weeks. At 11 weeks, plasma renin activity (PRA) and serum
      aldosterone were determined, and the animals were killed. Kidney sections were
      scored for glomerular and interstitial smooth muscle actin and glomerular desmin
      expression as early markers for renal damage. Mesangial matrix expansion was
      determined as a marker for structural damage. PRA and aldosterone levels were
      elevated in untreated Ren2 rats in comparison to SD controls. AT(1)-RA further
      increased PRA but decreased aldosterone. All parameters of renal damage were
      elevated in untreated Ren2 rats. Blood pressure was not elevated at week 7 in
      Ren2 and not affected by either treatment. Mild signs of hypertensive damage were
      found in untreated Ren2 rats. All interventions significantly diminished damage
      to glomerular epithelium and interstitium. In addition, AT(1) receptor and p38
      blockade reduced mesangial matrix expansion. In homozygous Ren2 rats, renal
      damage was ameliorated by a nonhypotensive dose of an AT(1)-RA and, similarly, by
      blockade of ERK or p38. This suggests that ERK and p38 are involved in AngII
      mediated renal damage.

PMID- 14691295
TI  - Absence of mutations of the BRAF gene and constitutive activation of
      extracellular-regulated kinase in malignant melanomas of the uvea.
AB  - The v-raf murine sarcoma viral homolog B1 (BRAF) gene, one of the human isoforms
      of RAF, is activated by Ras, leading to cooperative effects in cells responsive
      to growth factor signals. Recently, somatic missense mutations of the BRAF gene
      have been detected in more than 66% of malignant melanomas of the skin. We
      analyzed 42 malignant melanomas of the uvea, 3 corresponding liver metastases,
      and 10 cutaneous melanomas for possible BRAF mutations: after microdissection,
      mutation analysis of BRAF and KRAS was performed. The expression of extracellular
      regulated kinase 1 and 2 (ERK1/2), an important downstream point of convergence
      in the Ras-RAF-MEK-Erk pathway, was analyzed immunohistochemically.
      Interestingly, we failed to detect activating BRAF mutations in uvea melanomas
      and their corresponding liver metastases. There were no mutations of BRAF in
      corresponding non-neoplastic uvea specimens, although we detected three BRAF
      mutations in sporadic cutaneous melanoma that led to a substitution of valine by
      glutamic acid at position 599 (V599E). KRAS mutations were detected in 1 of 10
      cutaneous melanoma but not in uveal or metastatic melanoma. Despite the lack of
      activating mutations in the BRAF gene, we identified constitutively activated ERK
      in almost all (86%) uveal melanoma tissues tested but not in corresponding normal
      retina or uveal cells. Our data indicate that BRAF gene mutations are rare to
      absent events in uveal melanoma. The finding of activated Erk suggests a
      causative role for MAPK activation in uveal melanoma independent of activating
      BRAF or RAS mutations.

PMID- 14691296
TI  - Effects of Helicobacter pylori infection on the link between regenerating gene
      expression and serum gastrin levels in Mongolian gerbils.
AB  - Although regenerating gene (Reg) protein is reported to have a trophic effect on
      gastric epithelial cells, its involvement in human gastric diseases is not clear.
      We have recently shown that both gastrin and gastric mucosal inflammation enhance
      Reg gene expression in the fundic mucosa in rats. This study was designed to
      clarify whether Reg protein is involved in Helicobacter pylori-induced gastritis
      and whether Reg gene expression is linked to serum gastrin levels in this
      condition. Mongolian gerbils were inoculated with an H. pylori strain isolated
      from a gastric cancer patient. Four weeks later, some of the gerbils with H.
      pylori infection were eradicated by lansoprazole, amoxicillin, and
      clarithromycin. The time courses of changes in Reg gene expression, serum gastrin
      levels, gastric acidity, and histopathologic factors were examined. Four weeks
      after H. pylori infection, gastritis started spreading to the fundic mucosa, and
      gastric acidity started reducing. Serum gastrin levels and Reg mRNA expression in
      the fundus were significantly increased 6 weeks after infection. Reg mRNA
      expression in the fundus correlated significantly with both serum gastrin levels
      and the severity of fundic mucosal inflammation. After H. pylori eradication,
      serum gastrin levels and fundic mucosal inflammation were normalized, and the
      increase in Reg mRNA expression was abolished. The Reg gene is associated with
      hypergastrinemia and fundic mucosal inflammation and may be involved in H. pylori
      induced gastritis.

PMID- 14691297
TI  - Induction of intercellular adhesion molecule-1 on human brain endothelial cells
      by HIV-1 gp120: role of CD4 and chemokine coreceptors.
AB  - Central nervous system dysfunction is commonly observed in children with HIV-1
      infection, but the mechanisms whereby HIV-1 causes encephalopathy are not
      completely understood. We have previously shown that human brain microvascular
      endothelial cells (HBMEC) from children are responsive to gp120 derived from X4
      HIV-1 by increasing expression of intercellular adhesion molecule (ICAM)-1 and
      vascular cell adhesion molecule-1. However, the mechanisms involved in gp120
      mediated up-regulation of cell adhesion molecule expression is unclear. In the
      present study, we found that gp120 derived from both X4 and R5 HIV-1 induced
      increased expression of ICAM-1 on HBMEC, but the degree of this up-regulation
      differed among the various HBMEC isolates. The up-regulation of ICAM-1 was
      inhibited by anti-CD4 antibodies as well as by specific antibodies directed
      against chemokine receptors and small-molecule coreceptor inhibitors. Anti-CD4
      antibodies inhibited the increase in ICAM-1 expression mediated by gp120 derived
      from X4 and R5 HIV-1, whereas antibodies against chemokine receptors displayed a
      differential inhibition depending on the source of gp120. Both X4 and R5 gp120
      induced ICAM-1 expression was sensitive to pertussis toxin and involved the
      nuclear factor-kB pathway. These findings indicate a direct involvement of CD4
      and a differential involvement of chemokine receptors in the activation of
      pediatric HBMEC by X4 and R5 gp120. The activation of brain endothelium of
      children by HIV-1 protein gp120 by way of CD4 and chemokine receptors may have
      implications for the pathogenesis of HIV-1 encephalopathy in the pediatric
      population.

PMID- 14691298
TI  - Expression of placental leucine aminopeptidase and adipocyte-derived leucine
      aminopeptidase in human normal and malignant invasive trophoblastic cells.
AB  - We recently identified two novel aminopeptidases, placental leucine
      aminopeptidase (P-LAP) and adipocyte-derived leucine aminopeptidase (A-LAP).
      Enzymatically, P-LAP degrades oxytocin, vasopressin, and angiotensin III, while A
      LAP degrades angiotensin II and kallidin. In this study we investigated the
      expression and localization of P-LAP and A-LAP in human trophoblastic cells in
      the normal placenta (n = 26), gestational choriocarcinoma (n = 8), and placental
      site trophoblastic tumor (n = 3). On immunoblot analysis both P-LAP and A-LAP
      proteins were detected in normal placenta and five choriocarcinoma tissues, as
      well as in two choriocarcinoma cell lines. Immunohistochemical staining of normal
      placental tissues demonstrated that P-LAP was not only localized in villous
      syncytiotrophoblasts but also highly expressed in extravillous trophoblasts
      (EVTs) invading the decidua or maternal spiral arteries. The expression level of
      P-LAP on these invasive EVTs reached a maximum during the late first to second
      trimesters of pregnancy, and it decreased in the third trimester. Similarly, A
      LAP was strongly expressed in EVTs invading the decidua or spiral arteries in the
      second trimester of pregnancy, while it was weakly or moderately expressed in
      villous cytotrophoblasts or EVTs located in the cell columns. These two
      aminopeptidases were more strongly expressed in all eight choriocarcinomas and
      three placental site trophoblastic tumors and mainly localized to the
      intermediate-type trophoblastic tumor cells invading the uterine myometrium or
      stromal vessels. In summary P-LAP and A-LAP were predominantly expressed in the
      invasive phenotype of EVTs during placentation, as well as in the invasive tumor
      cells of trophoblastic neoplasms. These results suggest the involvement of these
      aminopeptidases in invasiveness of both normal and malignant intermediate-type
      trophoblasts possibly through degradation of specific peptide substrates.

PMID- 14691299
TI  - Human embryonic stem cells as an in vitro model for human vascular development
      and the induction of vascular differentiation.
AB  - Early embryonic blood vessels are typically composed of fragile tubes of
      endothelial cells encircled by vascular smooth muscle cells. Early human
      vasculogenesis was explored in spontaneous and directed differentiation models
      derived from human embryonic stem (HES) cells. In a 3-dimensional (3D) model, HES
      cells were studied for their potential for vascular differentiation during the
      spontaneous formation of embryoid bodies. Directed differentiation was
      investigated by means of a 2-dimensional (2D) differentiation method to promote
      vascular differentiation from HES cells (without the formation of embryoid
      bodies). Using this latter approach, up-regulation of early lineage markers of
      endothelial progenitors were induced. Additional culture under strict conditions
      and exposure to angiogenic growth factors resulted in a prolonged differentiation
      pathway into mature endothelial cells and up-regulation of vascular smooth muscle
      cell markers. The use of 3D collagen gels and Matrigel assays for the induction
      and inhibition of human vascular sprouting in vitro further established the
      vascular potential of the cells generated by the 2D differentiation system. Our
      study shows that HES cells can provide useful models to study early
      differentiation and development of blood vessels. Moreover, the 2D
      differentiation model facilitates both the production of vascular lineage cells
      from HES cells for various potential therapeutic applications and also provides a
      model for studying the mechanisms involved in early human embryonic blood vessel
      development.

PMID- 14691300
TI  - A novel in vitro model of trophoblast-mediated decidual blood vessel remodeling.
AB  - In vivo the extravillous trophoblasts (EVTs) penetrate the decidua and the first
      third of the myometrium to remodel the uterine spiral arteries and achieve the
      high-flow, low-resistance circulation characteristic of the intervillous space of
      the term placenta. Much of our understanding of these processes comes from
      histologic analysis of placental bed biopsies, a limited tissue source and one
      that can provide only a snapshot of a dynamic process. To better characterize
      these cellular interactions, we have developed an in vitro co-culture system in
      which first trimester villous explants are cultured at low oxygen tension in
      contact with 2-mm(2) sections of decidua parietalis from the same patient.
      Hematoxylin eosin counterstaining of paraffin sections shows that EVT columns
      form at the tips of the placental villi and adhere and penetrate the decidual
      surface. The decidual blood vessels in the path of the EVT show morphologic
      disruption. Immunohistochemical analysis of the co-cultures using both an
      endothelial specific anti-CD31 and an anti-smooth muscle actin antibody show a
      disruption of the integrity of the vessel lining together with a complete loss of
      organized smooth muscle actin surrounding the blood vessels. In contrast control
      decidua samples in the absence of placental villi exhibit blood vessels with a
      complete endothelial lining and an organized muscular sheath. Using both an anti
      cytokeratin-7 and anti-Cdx-2 antibody specific to trophoblasts, we show that
      these changes coincide with invasion of the vessels by endovascular trophoblasts
      and penetration of the decidua by interstitial EVTs. No EVTs were found in the
      control decidua. Thus we conclude that this in vitro model mimics the physiologic
      change observed in vivo during trophoblast invasion into maternal decidual
      tissues, and as such it may provide useful information concerning the
      interactions between EVTs and decidual cells and vessels during early gestation.

PMID- 14691301
TI  - Transcription of sonic hedgehog, a potential factor for gastric morphogenesis and
      gastric mucosa maintenance, is up-regulated in acidic conditions.
AB  - Gastric body mucosa atrophy predisposes one to gastric cancer. Disturbances in
      the gastric differentiation process might play a role in the evolution of gastric
      atrophy. Sonic hedgehog (Shh) has recently been implicated as a crucial factor in
      gastric organogenesis and gland differentiation. In this study we investigated
      the expression of key factors in the Shh pathway, namely Shh and its receptor
      Patched (Ptc), in normal and pathologic stomach mucosa. Furthermore, the
      potential role of pH for Shh dysregulation was analyzed. Ten gastric biopsy
      specimens each from normal gastric mucosa, chronic nonatrophic gastritis,
      atrophic gastritis, and gastric cancer were included. Expression of Shh and Ptc
      was analyzed by immunohistochemistry. In normal body mucosa and in nonatrophic
      body gastritis, Shh was strongly expressed in parietal cells. Ptc was also
      expressed in gastric chief cells. Shh expression was almost completely lost in
      atrophic gastritis and in gastric cancer and absent in intestinal metaplasia. Ptc
      was markedly reduced in atrophy and only weakly positive in intestinal metaplasia
      and gastric cancer. In in vitro experiments, gastric cancer cell line 23132 was
      found positive for Shh. In long-term culture as well as in culture conditions
      with low pH, transcription of Shh in 23132 was significantly increased in
      quantitative reverse transcription PCR analyses. We concluded that the decreased
      expression of the Shh pathway in atrophic gastritis and gastric cancer might
      reflect altered differentiation processes within the gastric unit and contributes
      to the development of gastric atrophy. The increase of gastric pH might play a
      role in the development of gastric mucosa atrophy via reduction of Shh
      transcription.

PMID- 14691302
TI  - Programmed cell death in rheumatoid arthritis peripheral blood T-cell
      subpopulations determined by laser scanning cytometry.
AB  - Because peripheral blood mononuclear cells play an important role in the
      perpetuation of the autoimmune process in rheumatoid arthritis (RA) and because
      the maintenance of these cells might be caused by the dysregulation of apoptosis,
      we investigated the apoptosis susceptibility of peripheral blood mononuclear
      cells from patients with RA. Freshly separated peripheral blood lymphocytes were
      stained for apoptosis markers (CD95, Bax, Bcl-2, TNF receptor) and for an
      activation marker (CD45-RO), and the apoptosis frequency of cells bearing these
      markers were assessed by the terminal-deoxynucleotidyl transferase-mediated dUTP
      digoxigenin nick end labeling method and nuclear condensation analysis with laser
      scanning cytometry. Also, the ability of CD4(+) and CD8(+) T-cell populations to
      undergo apoptosis was investigated with 24-hour culture in medium alone or with
      different apoptosis inducers (anti-CD3, anti-CD95, anti-TNF receptor). Laser
      scanning cytometry analysis was used to enumerate the phenotype and apoptosis
      ratios of both freshly isolated and cultured lymphocytes. Quantitative ELISA was
      performed to detect plasma levels of TNF-alpha and soluble Fas ligand.
      Furthermore, we studied the relationship between marked apoptotic defects in
      patients with RA and the severity of clinical disease. CD4(+) T-cell counts in
      patients with RA were elevated compared with controls. A decreased rate of anti
      CD95-mediated apoptosis was found within the CD4(+) and CD8(+) lymphocytic
      subpopulations. In patients with RA, decreased Bax expression and decreased
      apoptosis rate within the Bax-positive cells were found, whereas Bcl-2 expression
      was elevated. The CD45-RO expression was higher, whereas the apoptosis within
      CD45-RO(+) cells were decreased in RA. Evaluation of plasma soluble Fas ligand
      revealed significantly decreased levels in patients compared with controls. The
      reduced susceptibility to CD95-mediated apoptosis may contribute to the expansion
      of an activated CD4(+) lymphocyte subpopulation and thus to the maintenance of
      peripheral autoreactive T-cell clones in RA. We also revealed a relationship
      between in vitro demonstrated lymphocyte apoptosis defects and clinical disease
      activity.

PMID- 14691303
TI  - Activated proliferation of B-cell lymphomas/leukemias with the SHP1 gene
      silencing by aberrant CpG methylation.
AB  - Previously we showed reduced protein and mRNA expression of the SHP1 gene in
      lymphoma/leukemia cell lines and patient specimens by Northern blot, RT-PCR,
      Western blot, and immunohistochemical analyses. In this study, aberrant
      methylation in the SHP1 gene promoter was detected in many B-cell
      leukemia/lymphoma cell lines as well as in patient specimens, including diffuse
      large B-cell lymphoma (methylation frequency 93%), MALT lymphoma (82%), mantle
      cell lymphoma (75%), plasmacytoma (100%) and follicular lymphoma (96%) by
      methylation-specific PCR, bisulfite sequencing, and restriction enzyme-mediated
      PCR analyses. The methylation frequency was significantly higher in high-grade
      MALT lymphoma cases (100%) than in low-grade MALT lymphoma cases (70%), which
      correlated well with the frequency of no expression of SHP1 protein in high-grade
      (80%) and low-grade MALT lymphoma (54%). It suggests that the SHP1 gene silencing
      with aberrant CpG methylation relates to the lymphoma progression. SHP1 protein
      expression was recovered in B-cell lines after the treatment of the demethylating
      reagent: 5-aza-2'-deoxycytidine. Transfection of the intact SHP1 gene to the
      hematopoietic cultured cells, which show no expression of the SHP1 gene, induced
      growth inhibition, indicating that gene silencing of the SHP1 gene by aberrant
      methylation plays an important role to get the growth advantage of the malignant
      lymphoma/leukemia cells. The extraordinarily high frequency (75 to 100%) of CpG
      methylation of the SHP1 gene in B-cell lymphoma/leukemia patient specimens
      indicates that the SHP1 gene silencing is one of the critical events to the onset
      of malignant lymphomas/leukemias as well as important implications for the
      diagnostic or prognostic markers and the target of gene therapy. These data
      support the possibility that the SHP1 gene is one of the tumor suppressor genes.

PMID- 14691304
TI  - APC haploinsufficiency, but not CTNNB1 or CDH1 gene mutations, accounts for a
      fraction of familial adenomatous polyposis patients without APC truncating
      mutations.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant condition
      characterized by the development of hundreds to thousands of colorectal
      adenomatous polyps. In addition to the classic form, there is also attenuated
      polyposis (attenuated adenomatous polyposis coli; AAPC), which is characterized
      by a milder phenotype. FAP/AAPC is caused by germline mutations in the
      adenomatous polyposis coli (APC) gene. Very recently, germline mutations in the
      base-excision repair gene MYH have been associated with recessive inheritance of
      multiple colorectal adenomas in a subset of patients. APC pathogenic alterations
      are mostly (>95%) represented by frameshift or nonsense mutations leading to the
      synthesis of a truncated protein. We identified 20 APC truncating mutation
      carriers out of 30 FAP/AAPC patients from different Italian kindreds. In the
      remaining 10 patients, we searched for alterations other than truncating
      mutations by enzymatic mutation detection, real-time quantitative RT-PCR, and
      genotyping of polymorphic markers encompassing the APC locus. Moreover, to assess
      whether mutations of genes interacting with APC can substitute or act in
      association with APC alterations, we sequenced both CTNNB1 (beta-catenin) and
      CDH1 (E-cadherin) genes. No CTNNB1 or CDH1 mutations were found. On the contrary,
      four patients showed a reduced APC gene expression compared with healthy
      subjects. In three of the four cases, genotyping results were compatible with a
      constitutive allelic deletion. In one case this conclusion was confirmed by
      haplotype segregation analysis. Our results support the notion that FAP/AAPC can
      result from APC constitutive haploinsufficiency, with gene deletion being a
      possible cause of reduced gene expression.

PMID- 14691305
TI  - Loss of heterozygosity and mutational analyses of the ACTRII gene locus in human
      colorectal tumors.
AB  - The activin type II receptorgene (ACTRII) is mutated in 58.1% of microsatellite
      unstable (MSI-H) colorectal cancers and is a close relative of the TGFbeta-1 type
      II receptor, which is known to be involved in both MSI-H and non-MSI-H colorectal
      carcinogenesis. We therefore sought to determine whether ACTRII was involved in
      non-MSI-H colorectal cancers. We evaluated ACTRII inactivation by allelic
      deletion, loss of mRNA expression, or somatic mutation in 51 non-MSI-H colon
      cancers. Loss of heterozygosity (LOH) at the ACTRII locus (2q23.1) was found in 9
      (17.6%) of 51 primary tumors. Loss of ACTRII mRNA expression was seen in one
      (14.3%) of the seven LOH-positive primary tumors from which total RNA was
      available. We also performed DNA sequencing analysis of tumors showing LOH. One
      LOH-positive primary tumor exhibited a novel germline missense sequence
      alteration (amino acid substitution, 117 Ile to Phe) that was not found in 23
      additional normal individuals, implying that this alteration is not a frequent
      polymorphism. We conclude that ACTRII is probably involved in both non-MSI-H and
      MSI-H colorectal carcinogenesis, but more frequently in the latter subgroup.

PMID- 14691306
TI  - VEGF(121) and VEGF(165) regulate blood vessel diameter through vascular
      endothelial growth factor receptor 2 in an in vitro angiogenesis model.
AB  - Vascular endothelial growth factor (VEGF) is essential for the induction of
      angiogenesis and drives both endothelial cell (EC) proliferation and migration.
      It has been suggested that VEGF also regulates vessel diameter, although this has
      not been tested explicitly. The two most abundant isoforms, VEGF(121) and
      VEGF(165), both signal through VEGF receptor 2 (VEGFR-2). We recently optimized a
      three-dimensional in vitro angiogenesis assay using HUVECs growing on Cytodex
      beads and embedded in fibrin gels. Fibroblasts provide critical factors that
      promote sprouting, lumen formation, and vessel stability. Using this assay, we
      have examined the role of VEGF in setting vessel diameter. Low concentrations of
      both VEGF(121) and VEGF(165) promote growth of long, thin vessels, whereas higher
      concentrations of VEGF remarkably enhance vessel diameter. Placental growth
      factor, which binds to VEGFR-1 but not VEGFR-2, does not promote capillary
      sprouting. Moreover, specific inhibition of VEGFR-2 signaling results in a
      dramatic reduction of EC sprouting in response to VEGF, indicating the critical
      importance of this receptor. The increase in vessel diameter is the result of
      cell proliferation and migration, rather than cellular hypertrophy, and likely
      depends on MEK1-ERK1/2 signaling. Both phosphatidylinositol 3-kinase and p38
      activity are required for cell survival. We conclude that the diameter of new
      capillary sprouts can be determined by the local concentration of VEGF and that
      the action of VEGF on angiogenic EC in this assay is critically dependent on
      signaling through VEGFR-2.

PMID- 14691308
TI  - SRC-induced disintegration of adherens junctions of madin-darby canine kidney
      cells is dependent on endocytosis of cadherin and antagonized by Tiam-1.
AB  - The effects of Src tyrosine kinase activation in subconfluent temperature
      sensitive (ts)-Src-transformed Madin-Darby canine kidney (MDCK) cells were
      analyzed by shifting them from nonpermissive (40.5 degrees C) to permissive (35
      degrees C) temperature. Already, in 15 minutes, adherens junction components were
      released from the lateral walls and accumulated to basal surfaces.
      Simultaneously, membranous actin staining vanished, actin bundles appeared at the
      basal surface, and the cells flattened. The only component phosphorylated and
      translocated after the shift to 35 degrees C was p120ctn. The epithelial
      mesenchymal transition could be inhibited by a specific inhibitor of Src kinase,
      PP2, or by inhibiting endocytosis. Therefore, Src activation was responsible for
      the transition, but not because of phosphorylation of adherens junction
      components but by way of activation of endocytic machinery and RhoGTPase.
      Expression of an RacGEF, Tiam-1 (T-lymphoma invasion and metastasis gene 1),
      prevented flattening of Src-transformed MDCK cells at 35 degrees C and resulted
      in accumulation of cadherin to lateral membranes. In the case where the Src-MDCK
      cells were cultivated at 35 degrees C and shifted for short time periods to 40.5
      degrees C, cadherin rapidly returned to lateral membranes, whereas actin and
      p120ctn followed hours afterward. This further supports the view that cadherin
      internalization is the primary target of Src kinase. We also looked at the cell
      morphology and distribution of cadherin and Tiam-1 in cells grown in three
      dimensional gels composed of collagen and laminin or in Matrigel. At
      nonpermissive temperature, both Src-MDCK and Tiam-1-transfected Src-MDCK cells
      exhibited nonpolarized morphology in collagen I, a loose cluster in the mixture
      of collagen I and laminin, and a differentiated cyst in Matrigel. In growth
      factor-depleted Matrigel, the Src-MDCK cells grew in nondifferentiated clusters,
      whereas Tiam-1-transfected cells went to apoptosis. The differentiated phenotype
      of both cell lines could be rescued by Matrigel-conditioned medium, platelet
      derived growth factor, or cholera toxin. Concomitantly, both cadherin and Tiam-1
      were recruited to lateral membranes. Therefore, cadherin and Tiam-1 seem to be
      the key players in the differentiation process of MDCK cells.

PMID- 14691307
TI  - Matrix metalloproteinase-21 is expressed epithelially during development and in
      cancer and is up-regulated by transforming growth factor-beta1 in keratinocytes.
AB  - Human matrix metalloproteinase-21 (MMP-21), the newest member of the MMP gene
      family, has been suggested to play an important role in embryogenesis and tumor
      progression and to be a target of the Wnt, Pax, and Notch signaling pathways.
      Here we report detection of MMP-21 by RT-PCR in mouse embryos aged 10.5, 12.5,
      13.5, and 16.5 days, as well as in various adult murine organs. In both humans
      and mice, MMP-21 protein was detected in the epithelial cells of developing
      kidney, intestine, neuroectoderm, and skin but not in normal adult skin using
      immunohistochemistry with two unrelated antibodies. However, it was present in
      invasive cancer cells of aggressive subtypes of basal and squamous cell
      carcinomas, although it was not expressed in skin disorders characterized by mere
      keratinocyte hyperproliferation. Of several cytokines tested, transforming growth
      factor-beta1 induced MMP-21 in vitro in HaCaTs and keratinocytes as judged by
      real-time quantitative TaqMan PCR. Although suprabasal differentiating
      keratinocytes expressed MMP-21 in developing skin in vivo, MMP-21-positive
      keratinocytes were detected by immunohistochemistry in both low and high calcium
      cultures. MMP-21 expression was not up-regulated by ras transformation in HaCaT
      cell lines (HaCaT, A5, II-4, and RT3); in skin and colon cancers, its expression
      did not associate with apoptosis, beta-catenin transactivation, or epithelial
      MMPs-9 and -10. However, MMP-21 protein was found in the same regions as MMP-7
      but not in the same cells. Our results suggest that during development, MMP-21
      expression is temporally and spatially tightly controlled. Unlike many classical
      MMPs, it is present in various normal adult tissues. Among epithelial MMPs, MMP
      21 has a unique expression pattern in cancer.

PMID- 14691309
TI  - Willet M. Hays, great benefactor to plant breeding and the founder of our
      association.
AB  - Willet M. Hays was a great benefactor to plant breeding and the founder of the
      American Genetic Association (AGA). We commemorate the AGA's centennial. We mined
      university archives, U.S. Department of Agriculture (USDA) yearbooks, plant
      breeding textbooks, scientific periodicals, and descendants for information.
      Willet Hays first recognized the individual plant as the unit of selection and
      started systematic pure-line selection and progeny tests in 1888. He developed
      useful plant breeding methods. He selected superior flax (Linum usitatissimum
      L.), wheat (Triticum vulgare L.), corn (Zea mays L.), barley (Hordeum vulgare
      L.), and oat (Avena sativa L.) varieties, and discovered Grimm alfalfa (Medicago
      sativa L.); all became commercially important. He initiated branch stations for
      better performance testing. Willet Hays befriended colleagues in other
      universities, in federal stations, in a London conference, and in Europe. He
      gathered and spread the scientific plant breeding gospel. He also improved rural
      roads and initiated animal breeding records and agricultural economics records.
      He started the AGA in 1903, serving as secretary for 10 years. He became
      assistant secretary of agriculture in 1904. He introduced the project system for
      agricultural research. He authored or coauthored the Nelson Amendment, the Smith
      Lever Act, the Smith-Hughes Act, and the protocol leading to the United Nations
      Food and Agriculture Organization-all involved teaching agricultural practices
      that improved the world.

PMID- 14691310
TI  - The genetic basis of a flower color polymorphism in the common morning glory
      (Ipomoea purpurea).
AB  - The common morning glory (Ipomoea purpurea) is highly polymorphic for flower
      color. Part of this phenotypic variation is due to allelic variation at the P
      locus. This locus determines whether flowers will be purple or pink, where purple
      is dominant to pink. We have determined that the anthocyanin biosynthetic gene
      flavonoid 3'-hydroxylase (f3'h) corresponds to the P locus. In the pink allele of
      f3'h there is a large insertion in the third exon, which results in the
      production of a truncated transcript. This shortened transcript produces a
      nonfunctional F3'H enzyme, resulting in the production of pink flowers rather
      than purple. In addition, we describe a polymerase chain reaction (PCR)-based
      assay that can be used to determine the genotype of a plant at this locus.

PMID- 14691311
TI  - Characterization and inheritance of the Anthocyanin fruit (Aft) tomato.
AB  - Tomato (Lycopersicon esculentum) accession LA1996 with the Anthocyanin fruit
      (Aft) gene has dark green foliage, elevated anthocyanin expression in the
      hypocotyls of seedlings, and anthocyanin in the skin and outer pericarp tissues
      of the fruit. Interest in the health benefits and antioxidant capacity of
      anthocyanins led to this study of the genetic potential for increased levels of
      this important class of phytonutrients in tomato fruit. In order to conform to
      tomato gene nomenclature rules, we propose changing the symbol Af for Anthocyanin
      fruit to Aft. Segregation ratios of anthocyanin expression in F(2) and BC(1)
      populations of a cross between the processing tomato UC82B and LA1996 were
      consistent with a single dominant gene hypothesis. Anthocyanin expression was
      reduced in backcross populations compared to F(2 )populations. Anthocyanin
      concentration, as measured by the pH differential method, of pigment-rich
      pericarp and skin tissues from LA1996 was estimated to be 20.6 mg/100 g and 66.5
      mg/100 g, respectively. Anthocyanidin composition was characterized by high
      performance liquid chromatography (HPLC). Fruit of accession LA1996 contained
      predominantly petunidin, followed by malvidin and delphinidinin. Lycopene, beta
      carotene, phytoene, and phytofluene levels were similar to those of normal
      tomatoes and lower than those found in high pigment tomatoes.

PMID- 14691312
TI  - Population genetic structure of Anopheles arabiensis mosquitoes in Ethiopia and
      Eritrea.
AB  - This study examined the population genetic structure of the major malaria vector,
      Anopheles arabiensis mosquitoes, in Ethiopia and Eritrea. Ethiopia and Eritrea
      have great geographical diversity, with high mountains, rugged plateaus, deep
      gorges, and rolling plains. The plateau is bisected diagonally by the Great Rift
      Valley into the Northwestern Highlands and the Southeastern Highlands. Five A.
      arabiensis populations from the Northwestern Highlands region and two populations
      from high-altitude sites in the Great Rift Valley were genotyped using six
      microsatellite markers to estimate the genetic diversity and population genetic
      structure of A. arabiensis. We found that A. arabiensis populations from the
      Northwestern Highlands and the Great Rift Valley region showed a similar level of
      genetic diversity. The genetic differentiation (F(ST)) of the five mosquito
      populations within the Northwestern Highlands region was 0.038 (P <.001), while
      the two populations within the Great Rift Valley showed little genetic
      differentiation (F(ST) = 0.007, P <.01). The degree of genetic differentiation
      between the Northwestern Highlands region and the Great Rift Valley region was
      small but statistically significant (F(ST) = 0.017, P <.001). The population
      genetic structure of A. arabiensis in the study area did not follow the isolation
      by-distance model (r(2) = 0.014, P >.05). The low F(ST) estimates for A.
      arabiensis populations in Ethiopia and Eritrea are consistent with the general
      population genetic structure of this species in East Africa based on other
      molecular markers.

PMID- 14691313
TI  - Evolutionary rearrangement of the amylase genomic regions between Drosophila
      melanogaster and Drosophila pseudoobscura.
AB  - Two Drosophila pseudoobscura genomic clones have sequence similarity to the
      Drosophila melanogaster amylase region that maps to the 53CD region on the D.
      melanogaster cytogenetic map. The two clones with similarity to amylase map to
      sections 73A and 78C of the D. pseudoobscura third chromosome cytogenetic map.
      The complete sequences of both the 73A and 78C regions were compared to the D.
      melanogaster genome to determine if the coding region for amylase is present in
      both regions and to determine the evolutionary mechanism responsible for the
      observed distribution of the amylase gene or genes. The D. pseudoobscura 73A and
      78C linkage groups are conserved with the D. melanogaster 41E and 53CD regions,
      respectively. The amylase gene, however, has not maintained its conserved linkage
      between the two species. These data indicate that amylase has moved via a
      transposition event in the D. melanogaster or D. pseudoobscura lineage. The
      predicted genes within the 73A and 78C regions show patterns of molecular
      evolution in synonymous and nonsynonymous sites that are consistent with previous
      studies of these two species.

PMID- 14691314
TI  - Phylogenetic relationships of the phasianidae reveals possible non-pheasant taxa.
AB  - The phylogenetic relationships of 21 pheasant and 6 non-pheasant species were
      determined using nucleotide sequences from the mitochondrial cytochrome b gene.
      Maximum parsimony and maximum likelihood analysis were used to try to resolve the
      phylogenetic relationships within Phasianidae. Both the degree of resolution and
      strength of support are improved over previous studies due to the testing of a
      number of species from multiple pheasant genera, but several major ambiguities
      persist. Polyplectron bicalcaratum (grey peacock pheasant) is shown not to be a
      pheasant. Alternatively, it appears ancestral to either the partridges or
      peafowl. Pucrasia macrolopha macrolopha (koklass) and Gallus gallus (red jungle
      fowl) both emerge as non-pheasant genera. Monophyly of the pheasant group is
      challenged if Pucrasia macrolopha macrolopha and Gallus gallus are considered to
      be pheasants. The placement of Catreus wallichii (cheer) within the pheasants
      also remains undetermined, as does the cause for the great sequence divergence in
      Chrysolophus pictus obscurus (black-throated golden). These results suggest that
      alterations in taxonomic classifications may be required for some pheasant
      species and genera.

PMID- 14691315
TI  - Restricted gene flow in Calomys musculinus (Rodentia, Muridae), the natural
      reservoir of Junin virus.
AB  - Random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) markers
      were used to evaluate the relative contribution of gene flow as a determinant of
      the population genetic structure of the wild rodent Calomys musculinus (the
      reservoir of Argentine hemorrhagic fever [AHF]) in central Argentina. One hundred
      eighty-seven individuals from 13 populations (9 of them from the endemic zone of
      AHF and 5 from areas outside it) were analyzed using 78 polymorphic RAPD loci.
      Genetic variation within each population was high; each individual was
      characterized by a unique RAPD phenotype. C. musculinus populations showed a
      moderate to high genetic subdivision and a random pattern of differentiation.
      Populations separated by the same geographic distance showed very different
      degrees of genetic divergence. The results indicate that populations of C.
      musculinus have colonized their present ranges relatively recently and
      differentiation by genetic drift has proceeded faster than homogenization by gene
      flow at the macrogeographic scale analyzed (10-700 km).

PMID- 14691317
TI  - AFLP to assess genetic variation in laboratory gerbils (Meriones unguiculatus).
AB  - The amplified fragment length polymorphism (AFLP) technique has been increasingly
      employed for characterizing inbred breeds of animals and detecting strain
      specific polymorphisms. The majority of animals studies conducted in biomedical
      research are performed on rodent species, among which laboratory-reared Mongolian
      gerbils can be included. Despite the wide use of gerbils in scientific studies,
      their genetics has rarely been studied. Therefore we investigated the genetic
      differentiation of laboratory bred gerbils by means of AFLP markers. Six
      EcoRI/TaqI primer combinations were selected among 13 different combinations to
      assess the genetic polymorphisms in four stocks of animals: Charles River (CR),
      Harlan (Ha), Parma (Pr), and Crossbred (Cb). CR and Ha gerbils were purchased
      from commercial vendors, while Pr and Cb were derived from animals bred in our
      animal colony. A total of 228 fragments ranging between 70 and 650 bp were
      obtained. The mean percentage of polymorphic loci across primer combinations was
      7.5%. Calculation of genetic distances through application of different
      algorithms (Nei's, BSI, and Jaccard's indexes) confirmed the poor genetic
      diversity between stocks. Nevertheless, a differentiation of the Pr and Cb stocks
      from the more homogeneous CR and Ha was revealed, in agreement with the different
      breeding derivation and management of the stocks.

PMID- 14691316
TI  - Mapping of QTL for Body Conformation and Behavior in Cattle.
AB  - Genome scans for quantitative trait loci (QTL) in farm animals have concentrated
      on primary production and health traits, and information on QTL for other
      important traits is rare. We performed a whole genome scan in a granddaughter
      design to detect QTL affecting body conformation and behavior in dairy cattle.
      The analysis included 16 paternal half-sib families of the Holstein breed with
      872 sons and 264 genetic markers. The markers were distributed across all 29
      autosomes and the pseudoautosomal region of the sex chromosomes with average
      intervals of 13.9 cM and covering an estimated 3155.5 cM. All families were
      analyzed jointly for 22 traits using multimarker regression and significance
      thresholds determined empirically by permutation. QTL that exceeded the
      experiment-wise significance threshold (5% level) were detected on chromosome 6
      for foot angle, teat placement, and udder depth, and on chromosome 29 for
      temperament. QTL approaching experiment-wise significance (10% level) were
      located on chromosome 6 for general quality of feet and legs and general quality
      of udder, on chromosome 13 for teat length, on chromosome 23 for general quality
      of feet and legs, and on chromosome 29 for milking speed. An additional 51 QTL
      significant at the 5% chromosome-wise level were distributed over 21 chromosomes.
      This study provides the first evidence for QTL involved in behavior of dairy
      cattle and identifies QTL for udder conformation on chromosome 6 that could form
      the basis of recently reported QTL for clinical mastitis.

PMID- 14691318
TI  - Cytomixis in pollen mother cells of Medicago sativa L.
AB  - Cytomixis (i.e., chromatin migration between meiocytes) has been detected in many
      plant species, but not in Medicago sativa spp. In the present study we report the
      identification of a few cytomictic alfalfa plants. Those plants, the "mother
      plants," were selfed and crossed with a normal control plant. Microsporogenesis
      analysis was performed on the mother plants, on the S(1) and F(1) plants, and on
      controls. The S(1) and F(1) plants, like the mother plants, were found to be
      cytomictic. Single or multiple chromatin bridges between two or more meiocytes
      were observed almost exclusively in prophase I. Some completely empty meiocytes
      were also observed. In addition to cytomixis, other meiotic abnormalities were
      found. Control plants showed an almost regular meiosis. The highest values of
      cytomixis were observed in the mother plants, and the lowest in their F(1)
      progenies. Variability of cytomixis in the F(1) plants is probably due to a
      heterozygotic condition of the parents for this trait. No significant correlation
      was found between cytomixis and pollen viability, even if the cytomictic plants
      showed low values of pollen viability.

PMID- 14691319
TI  - Effects of two-locus combinations, using the roux, lavender, and beige mutations,
      on plumage color of Japanese quail.
AB  - The interactions between the effects of three plumage color mutations taken two
      by-two (sex-linked recessive roux, autosomal recessive lavender, and autosomal
      dominant beige) were studied in Japanese quail by producing a total of 121 F(1)
      and 1118 F(2) quail from the three pure stocks. Three new plumage colors were
      obtained in F(2) quail: roux-diluted beige, cream, and lavender-diluted beige.
      Two of them, roux-diluted beige (from the roux and beige mutations) and cream
      (from the roux and lavender mutations) corresponded to double homozygotes or
      hemizygous birds, and could therefore be used to tag a quail line. On the other
      hand, an F(3) from F(2) birds with lavender-diluted beige plumage was necessary
      to show that quail with this plumage color were homozygous for the lavender
      mutation, but were either homozygous or heterozygous for the beige gene. In all
      three F(2)s, observed segregation of plumage colors fit simple two-locus
      Mendelian inheritance.

PMID- 14691320
TI  - Inheritance of resistance to clopyralid and picloram in yellow starthistle
      (Centaurea solstitialis L.) is controlled by a single nuclear recessive gene.
AB  - The noxious weed yellow starthistle (Centaurea solstitialis L.) can be controlled
      effectively at the seedling stage with foliar application of the auxinic
      herbicides picloram or clopyralid. Although resistance to these herbicides is
      rare, a yellow starthistle biotype resistant to picloram and cross-resistant to
      clopyralid was observed in 1989 near Dayton, WA, in a pasture that had been
      subjected to intensive picloram selective pressure. Our objective was to
      determine the mode of inheritance for this resistance trait. Transmission of the
      resistant phenotype was monitored in reciprocal F(1) crosses between susceptible
      (SCI) and resistant (RDW) plants, their testcross and pseudo-F(2) progeny.
      Progeny from all crosses, as well as RDW and SCI seedlings of original
      populations, were sprayed with picloram or clopyralid to distinguish between
      susceptible and resistant individuals. All F(1) progeny were susceptible to both
      herbicides, indicating that the resistance trait was of nuclear origin and
      recessive in nature. Segregation of the resistant phenotype among pseudo-F(2) and
      testcross progeny of F(1) genotypes demonstrated monofactorial inheritance (P
      >.25) for resistance to both herbicides. The conclusion that resistance is
      conferred by a single recessive allele is consistent with the observation that no
      other picloram-resistant yellow starthistle populations have been identified in
      the area since picloram selection pressure was abated.

PMID- 14691323
TI  - Topological density of nets: a direct calculation.
AB  - The topological density of a three-dimensional net is currently available after
      determining its entire coordination sequence. This paper shows that its value can
      be obtained directly from the set of cycles of the quotient graph of the net. A
      geometrical tool, the cycles figure of the net has been developed for this
      purpose. Its construction as a convex polyhedron with triangular faces is
      described as well as its use for topological density calculations. An exact
      expression is derived for three-dimensional nets and extended to arbitrary n
      dimensional nets. Additionally, this paper describes applications to three
      dimensional lattices and nets, n-dimensional diamonds and lonsdaleites.

PMID- 14691322
TI  - Numerically stable algorithms for the computation of reduced unit cells.
AB  - The computation of reduced unit cells is an important building block for a number
      of crystallographic applications, but unfortunately it is very easy to
      demonstrate that the conventional implementation of cell reduction algorithms is
      not numerically stable. A numerically stable implementation of the Niggli
      reduction algorithm of Krivy & Gruber [Acta Cryst. (1976), A32, 297-298] is
      presented. The stability is achieved by consistently using a tolerance in all
      floating-point comparisons. The tolerance must be greater than the accumulated
      rounding errors. A second stable algorithm is also presented, the minimum
      reduction, that does not require using a tolerance. It produces a cell with
      minimum lengths and all angles acute or obtuse. The algorithm is a simplified and
      modified version of the Buerger-reduction algorithm of Gruber [Acta Cryst.
      (1973), A29, 433-440]. Both algorithms have been enhanced to generate a change-of
      basis matrix along with the parameters of the reduced cell.

PMID- 14691324
TI  - On a fast calculation of structure factors at a subatomic resolution.
AB  - In the last decade, the progress of protein crystallography allowed several
      protein structures to be solved at a resolution higher than 0.9 A. Such studies
      provide researchers with important new information reflecting very fine
      structural details. The signal from these details is very weak with respect to
      that corresponding to the whole structure. Its analysis requires high-quality
      data, which previously were available only for crystals of small molecules, and a
      high accuracy of calculations. The calculation of structure factors using direct
      formulae, traditional for 'small-molecule' crystallography, allows a relatively
      simple accuracy control. For macromolecular crystals, diffraction data sets at a
      subatomic resolution contain hundreds of thousands of reflections, and the number
      of parameters used to describe the corresponding models may reach the same order.
      Therefore, the direct way of calculating structure factors becomes very time
      expensive when applied to large molecules. These problems of high accuracy and
      computational efficiency require a re-examination of computer tools and
      algorithms. The calculation of model structure factors through an intermediate
      generation of an electron density [Sayre (1951). Acta Cryst. 4, 362-367; Ten Eyck
      (1977). Acta Cryst. A33, 486-492] may be much more computationally efficient, but
      contains some parameters (grid step, 'effective' atom radii etc.) whose influence
      on the accuracy of the calculation is not straightforward. At the same time, the
      choice of parameters within safety margins that largely ensure a sufficient
      accuracy may result in a significant loss of the CPU time, making it close to the
      time for the direct-formulae calculations. The impact of the different parameters
      on the computer efficiency of structure-factor calculation is studied. It is
      shown that an appropriate choice of these parameters allows the structure factors
      to be obtained with a high accuracy and in a significantly shorter time than that
      required when using the direct formulae. Practical algorithms for the optimal
      choice of the parameters are suggested.

PMID- 14691325
TI  - Ultra-high-angle double-crystal X-ray diffractometry (U-HADOX) for determining a
      change in the lattice spacing: experiment.
AB  - An experiment is reported on ultra-high-angle double-crystal X-ray diffractometry
      (U-HADOX) at the Bragg angle theta up to 89.5 degrees, coupled with white X-rays
      from a conventional source. It is shown that the Bragg-peak shift associated with
      a change in the lattice spacing increases in proportion to tantheta as predicted;
      the relative accuracy of a change in the spacing to 10(-8) is attained. The
      performance is demonstrated for the determination of the linear thermal-expansion
      coefficient alpha of silicon and strontium titanate SrTiO(3), a value with four
      significant figures being determined with the data in a temperature range
      narrower than 1 K; the value of alpha for silicon (2.621 +/- 0.003) x 10(-6) K(
      1) at 300.4 K is compared with those in the literature based on experiments using
      the Bond method of X-ray diffraction and macroscopic thermal expansion. The
      advantages and characteristics of U-HADOX including the coupling with synchrotron
      X-rays are discussed.

PMID- 14691326
TI  - A Fourier optics approach to the dynamical theory of X-ray diffraction--perfect
      crystals.
AB  - A new formalism is presented concerning the dynamics of X-rays in crystals. It is
      based on Takagi's equations and Fourier optics; it also offers an alternative to
      the usual Ewald-von Laue approach. The article does not give new results but
      shows a new way to formulate the dynamical theory of X-ray diffraction. In
      addition, it proposes a novel description of X-ray propagation based on the
      analogy between the dynamics of X-rays in crystals and that of two-level quantum
      systems.

PMID- 14691327
TI  - Gamma-ray and neutron diffraction studies of CoF2: magnetostriction, electron
      density and magnetic moments.
AB  - Accurate structure factors up to sin theta/lambda = 1.6 A(-1) have been measured
      with 316.5 keV gamma-rays from CoF(2), both at room temperature and in the
      antiferromagnetic state at 10 K. The same crystal was used to collect extended
      time-of-flight neutron diffraction data in the two magnetic states, which allowed
      an accurate determination of the fluorine positional parameter. For room
      temperature, the standard structural parameters are reported. At 10 K, a complete
      charge-density study has been carried out. The total number of 3d electrons on Co
      is found to be 6.95 (3). The experimental populations of the d orbitals agree
      with expectation from crystal field theory. The fluorine valence region exhibits
      a strong dipolar deformation. Electronic properties at the bond critical points
      and integrated atomic properties are derived from the static model electron
      density, revealing the Co-F interactions as purely ionic. On magnetic ordering, a
      shift of the fluorine ions of 1.5 (4) x 10(-3) A is found which confirms a
      prediction from theory of optical birefringence. The effect of magnetostriction
      on the distortion of the ligand coordination octahedra is compared for the late
      members of the 3d transition-metal difluorides. From neutron powder diffraction,
      an ordered magnetic moment of 2.60 (4) mu(B) per cobalt ion is found. Despite the
      strong deviation from the ideal spin value of 3 mu(B), there is still an
      appreciable orbital contribution to the local magnetic moment.

PMID- 14691328
TI  - Dispersion corrections of the copper K edge measured by Fresnel diffraction.
AB  - Dispersion corrections to the atomic scattering factors for the copper K edge
      have been measured by a new technique, Fresnel diffraction. Fresnel diffraction
      fringes were measured at several sample-detector distances as a function of
      energy across the copper K-absorption edge. The dispersion corrections were
      obtained from optimizing a least-squares fit of Fresnel fringe simulations to the
      measured data.

PMID- 14691329
TI  - Phase-dependent polarization aspects of three-wave X-ray diffraction: an
      iterative Born approximation.
AB  - The iterative Born approximation is derived for three-wave dynamical X-ray
      diffraction. Dependence of the three-wave diffraction profiles of the diffracted
      wave on the polarization state of a linearly polarized incident wave is
      theoretically and experimentally investigated. General conditions of the phase
      sensitivity as well as the asymmetry of diffraction profiles are obtained from
      this approximation and compared with direct dynamical calculations. Reasonable
      qualitative agreement between the results obtained from this iterative approach
      and the exact dynamical calculation is shown. A new feature of reversing
      asymmetry of an intensity profile with respect to phase change is theoretically
      predicted.

PMID- 14691330
TI  - First-principles calculations as a tool for structure validation in electron
      crystallography.
AB  - The crystal structures of Ti(11)Se(4) [Weirich, Ramlau, Simon, Hovmoller & Zou
      (1996). Nature (London), 382, 144-146] and Ti(45)Se(16) [Weirich (2001). Acta
      Cryst. A57, 183-191] determined previously from selected-area electron
      diffraction (SAED) data have been checked for their correctness by means of total
      energy calculations within the non-local density functional theory. The
      reliability of the used method was verified by test calculations carried out for
      the structurally related compound Ti(8)Se(3), which is well known from single
      crystal X-ray diffraction [Weirich, Pottgen & Simon (1996). Z. Kristallogr. 212,
      929-930]. For Ti(8)Se(3), structural models from both experiment and calculation
      show a perfect match (average agreement 0.01 A). This proves that the geometrical
      optimized models from first-principles calculation can be used as a reliable
      alternative when good-quality X-ray results cannot be obtained. Calculations
      carried out for the two structures determined from electron crystallography
      yielded average improvement of the atomic coordinates of 0.04 and 0.09 A for
      Ti(11)Se(4) and Ti(45)Se(16), respectively. The optimized cell parameters of the
      monoclinic structures (both space group C2/m, No. 12) are a = 25.51, b = 3.43, c
      = 19.19 A, beta = 117.9 degrees for Ti(11)Se(4) and a = 36.31, b = 3.45, c =
      16.59 A, beta = 92.1 degrees for Ti(45)Se(16). These results prove that crystals
      that are too small for single-crystal X-ray diffraction and are difficult to
      solve by powder diffraction may nevertheless be amenable to accurate structure
      determination by electron diffraction structure analysis using data from standard
      SAED and the assumption of quasi-kinematical scattering. Moreover, this study
      shows that geometry optimization by first-principles calculations is the perfect
      tool for validation and improvement of complex structural models, which are
      suspected to have errors owing to the poor quality of experimental data.

PMID- 14691331
TI  - Ab initio crystal structure determination using X-ray fluorescence holography for
      different noise levels: numerical simulation and analysis.
AB  - X-ray fluorescence holography (XFH) two-dimensional angular scans with the
      fluorescing Cu atom of a Cu(3)Au single crystal for different noise levels have
      been calculated and the structure factors have been numerically restored,
      supporting the ab initio structure determination method first discussed by
      Chukhovskii & Poliakov [Acta Cryst. (2003), A59, 109-116]. In the case of
      resultant XFH scans where noise levels are up to the regular signal values at
      each angular scan point, the elaborated method is found to work well. With the
      use of the linear regression algorithm code [Chukhovskii & Poliakov Acta Cryst.
      (2003), A59, 109-116], the restored structure factors show clearly not just good
      accuracy of the restoration code procedure but also the efficiency of the
      structure-determination method that can utilize the XFH data even for high noise
      levels.

PMID- 14691332
TI  - Applied geminography--symmetry analysis of twinned crystals and definition of
      twinning by reticular polyholohedry.
AB  - The common classification of twinning into the four categories of twinning by
      merohedry (complete and exact overlap of the lattices of the twinned crystals),
      pseudomerohedry (complete but approximate overlap), reticular merohedry (partial
      but exact overlap) and reticular pseudomerohedry (partial and approximate
      overlap) is revised in terms of the complete (translational and point) lattice
      symmetry of the twin and of the individual. The new category of reticular
      polyholohedry is introduced for twins where the twin lattice has the same point
      symmetry but a different orientation of the individual lattice. It is shown that
      the degeneration to twin index 1 relates, in a parallel way, reticular merohedry
      to metric merohedry and reticular polyholohedry to syngonic merohedry. Some
      examples from the recent literature are analysed in terms of this revised
      classification.

PMID- 14691335
TI  - Endogenous nitric oxide reduces microvascular permeability and tissue oedema
      during exercise in cat skeletal muscle.
AB  - Based on a proposed increase in the release of the vasodilators nitric oxide (NO)
      and prostacyclin during exercise, and the fact that these substances have
      vascular permeability-reducing properties, this study was designed to evaluate
      (1) possible effects of exercise on hydraulic permeability, (2) whether
      permeability and muscle swelling are reduced by an increased release of NO and
      prostacyclin during exercise and (3) whether NO and prostacyclin are involved in
      exercise hyperaemia. The study was performed on an autoperfused cat calf muscle
      preparation with ligated lymph vessels, and exercise was induced by somatomotor
      nerve stimulation. Change in microvascular hydraulic permeability was estimated
      by a capillary filtration coefficient (CFC) technique. We found that the marked
      muscle volume increase after the start of the exercise gradually decreased,
      reaching an isovolumetric state within 25 min where CFC had decreased by about
      25% (p < 0.05). CFC recovered completely after exercise was stopped. The decrease
      in CFC was abolished during blockade of endogenous NO by the NO synthase
      inhibitor L-NAME, but was preserved during blockade of endogenous prostacyclin by
      tranylcypromine. The muscle volume increase during exercise was about 60% greater
      with L-NAME than during vehicle or tranylcypromine (p < 0.01). Neither L-NAME nor
      tranylcypromine had any effect on exercise hyperaemia. We conclude that
      microvascular hydraulic permeability is reduced during exercise, that this effect
      reduces exercise-induced muscle swelling, and that the effects are mediated via
      release of NO. NO and prostacyclin are not involved in exercise hyperaemia.

PMID- 14691336
TI  - Arterial structural changes in hypertension: a consideration of methodology,
      terminology and functional consequence.
AB  - Alteration of resistance artery geometric design is a hallmark of established
      hypertension. In particular, there is an increased media thickness: lumen
      diameter ratio. In this review, consideration is given to the methods available
      for assessment of vascular structure, the terminology used to describe vascular
      structural changes in hypertension and the possible functional consequences of
      altered arterial design in the maintenance of the hypertensive state. In light of
      these considerations, a number of proposals are made concerning quantification
      strategies and descriptor terminologies. In particular, a simple descriptor
      terminology is proposed that describes such structural differences but makes no
      assumptions concerning the underlying processes that account for altered arterial
      structure in hypertension.

PMID- 14691337
TI  - Structural abnormalities of the resistance vasculature in hypertension.

PMID- 14691338
TI  - Endothelium-dependent relaxant responses to selective 5-HT(1B/1D) receptor
      agonists in the isolated middle cerebral artery of the rat.
AB  - The vasomotor effects of triptans in the middle cerebral artery (MCA) of rats
      were studied using the pressurised arteriography method and in vitro vessel
      baths. Using the arteriograph, MCAs from Sprague-Dawley rats were mounted on two
      glass micropipettes, pressurised to 85 mm Hg and luminally perfused. Luminally
      added 5- hydroxytryptamine (5-HT), sumatriptan and rizatriptan induced maximal
      dilatations of 22 +/- 4, 10 +/- 2 and 13 +/- 5%, respectively, compared to the
      resting diameter. The relaxant effect of sumatriptan was blocked by the 5-
      HT(1B/1D) receptor selective antagonist GR 55562 (10(-6)M). The use of N(omega)
      nitro-L-arginine and charybdotoxin revealed that the dilatation involved both
      nitric oxide and endothelially derived hyperpolarising factor. Thus, the earlier
      demonstrated expression of 5-HT(1B/1D) immunoreactivity in the endothelium may
      well translate into a relaxant response to 5-HT and triptans. Using the vessel
      bath technique, MCA segments were mounted on two metal wires. The relaxant
      responses to sumatriptan could not be reproduced using this model; instead, weak
      contractile responses (6 +/- 3% of submaximal contractile capacity) were
      observed. The difference in observations between the experimental models may be
      related to the maintenance of shear stress in the arteriograph.

PMID- 14691339
TI  - Calcification of the medial layer of the internal thoracic artery in diabetic
      patients: relevance of glycoxidation.
AB  - OBJECTIVE: The aim of this study was to evaluate the role of glycoxidation in the
      calcification of the internal thoracic artery (ITA) in diabetes mellitus (DM).
      METHODS: ITA samples were obtained from 17 patients with type 2 DM (age 62.9 +/-
      10.5 years) and 12 age-matched, nondiabetic patients (age 62.5 +/- 10.2 years)
      who underwent coronary artery bypass grafting. These samples were analyzed
      histopathologically and assessed for calcification by von Kossa staining and for
      glycoxidation by immunohistochemistry using anti-N(epsilon)-(carboxymethyl)lysine
      (CML) antibody. Morphometric evaluation of calcification of the medial layer,
      intimal thickness and intima-to-media ratio was performed using NIH image
      software. To evaluate the mechanism of the interaction between calcification and
      glycoxidation, we developed an in vitro model of calcification of collagen that
      was chemically modified by glucose, glutaraldehyde or epoxy compound. The calcium
      binding activity of these collagens was determined in hydrolysates using atomic
      absorption spectrophotometry. RESULTS: ITAs of both diabetic and nondiabetic
      patients were free of atherosclerosis, and no differences were found between the
      two groups with regard to intimal thickness and intima-to-media ratio. Areas of
      calcification were noticed in both groups in the tunica media, but not in the
      tunica intima. Calcium deposits were localized within the extracellular matrix,
      which was immunohistochemically positive for CML. The extent of medial layer
      calcification was significantly greater in diabetic patients than nondiabetic
      subjects, but was independent of known risk factors such as hypertension,
      hyperlipidemia, obesity and history of old myocardial infarction. The binding
      activity of collagen was time-dependently increased with in vitro incubation of
      glucose. A significant increase in the calcium-binding ability was observed in
      glucose- and glutaraldehyde-modified collagens, but not in epoxy compound
      modified collagen. CONCLUSION: Our results suggest that glycoxidative
      modification of the extracellular matrix, in particular collagen, of the vascular
      wall may enhance the development of ITA calcification in diabetic patients.

PMID- 14691340
TI  - Relationships between serum IGF-1, IGFBP-2, interleukin-1beta and interleukin-6
      in inflammatory bowel disease.
AB  - AIMS: To study the relationships between serum IGF-1, IGFBP-3 and IGFBP-2 and
      interleukin (IL)-1beta and IL-6 in inflammatory bowel disease (IBD). METHODS:
      Thirty-seven patients (18 males, 19 females, aged 8.8-26.1 years) with IBD
      (Crohn's disease, CD, n = 17, and ulcerative colitis, UC, n = 20) were studied.
      Patients were in relapse or remission according to established criteria. Serum
      IGF-1, IGFBP-3, IGFBP-2, IL-1beta and IL-6 levels were determined in patients and
      15 healthy controls (aged 8.2-19.0 years). RESULTS: IGF-1 levels were lower in
      patients with CD in relapse compared with controls (p < 0.05). IGFBP-2 levels
      were higher in CD in relapse compared with other groups (all p < 0.05). In CD and
      UC patients (n = 37), IGF-1 levels were inversely correlated with the erythrocyte
      sedimentation rate (ESR) and C-reactive protein (CRP). IGFBP-2 levels correlated
      positively with ESR and IL-1beta. IL-6 levels correlated positively with ESR and
      CRP. IL-1beta levels were elevated in CD in relapse compared to controls (p <
      0.05) and were higher in UC in relapse than in other groups (all p < 0.05). In
      combined CD/UC patients in relapse (n = 20), IL-1beta levels were higher (p <
      0.05) in patients with recto-sigmoiditis (n = 5) than in other patients.
      CONCLUSIONS: IGF-1, IGFBP-2 levels were related to IL levels, disease activity
      and anatomical distribution, consistent with active inflammation modifying the
      IGF-IGFBP system, possibly relevant to disturbance of growth.

PMID- 14691341
TI  - The role of c-jun protein in proliferation and apoptosis of the endometrium
      throughout the menstrual cycle.
AB  - Proliferation and apoptosis of the endometrium throughout the menstrual cycle
      were evaluated. Sections from 30 premenopausal women were examined using
      antibodies of c-jun protein, c-fos protein, estrogen receptors alpha and beta (ER
      alpha and ER-beta), progesterone receptor (PR), and Ki-67. Apoptotic cells were
      identified using a modified terminal deoxynucleotidyl-transferase-mediated
      biotinylated deoxyuridine triphosphate nick-end labeling (TUNEL) method. The
      cyclic changes of c-jun protein, c-fos protein, ER-alpha, PR, and Ki-67 were
      shown in glandular epithelial cells. Although the stromal expression of ER-alpha
      decreased during the secretory phase, a high stromal expression of c-jun protein
      and PR was still observed during the late secretory phase. The expression of ER
      beta appeared lower as compared with that of ER-alpha, without a cyclic change.
      The apoptotic index was significantly elevated in the glandular epithelial cells
      of the late secretory phase, whereas a few apoptotic cells were detected in the
      stromal cells at any stage of the cycle. The cyclic change of c-jun protein
      probably plays an important role in proliferation and apoptosis of glandular
      epithelial cells. The persistent stromal expression of c-jun protein and PR is
      thus considered to prevent stromal cells from entering into apoptosis during the
      late secretory phase.

PMID- 14691342
TI  - Pregnancy outcome in patients with a history of recurrent spontaneous
      miscarriages and documented thrombophilias.
AB  - The aim of this study was to evaluate the effect of treatment in patients
      analyzed for recurrent spontaneous miscarriage with a diagnosis of a hereditary
      thrombophilia, the presence of antiphospholipid and/or autoimmune antibodies,
      and/or hyperhomocystinemia (HHC) with or without methylenetetrahydrofolate
      reductase (MTHFR) polymorphisms. In total, 76 women with 2 or more embryonic or
      fetal losses were analyzed. Of these, 49 (64.4%) women were found to have one or
      more thrombophilias and/or autoimmune antibodies, and 33 (43.4%) women were found
      to have a MTHFR polymorphism and/or HHC. Since completion of the recurrent
      miscarriage analysis, 39 women conceived again. All women with a thrombophilia
      were treated with low-dose aspirin plus low molecular weight heparin. All women
      with previously diagnosed HHC and/or MTHFR polymorphisms were treated with folate
      and vitamin B(6) and B(12) supplementation. In the thrombophilia group, 27 women
      conceived resulting in 20 successful pregnancies (74.1%) and 7 pregnancy losses
      (2 trisomy 16, 1 ectopic pregnancy and 4 unexplained miscarriages), i.e. an
      unexplained pregnancy loss rate of 14.8%. In the HHC/MTHFR group 22 women
      conceived, resulting in 17 successful pregnancies (77.3%) and 5 pregnancy losses
      (1 trisomy 16, 1 Turner syndrome and 3 unexplained miscarriages), i.e. an
      unexplained pregnancy loss rate of 13.6%.

PMID- 14691343
TI  - Prediction of adverse neonatal outcomes in preeclampsia by absent or reversed end
      diastolic flow velocity in the umbilical artery.
AB  - To evaluate the independent contribution of absent or reversed end-diastolic
      umbilical artery Doppler flow (AREDF) in the prediction of subsequent adverse
      neonatal outcomes, we performed Doppler examinations on 270 preeclamptic women
      with a singleton pregnancy. The end-point variables were low Apgar scores and
      adverse neonatal outcomes (respiratory distress syndrome, intracranial
      hemorrhage, sepsis, seizures, jaundice, hypoglycemia, hypocalcemia,
      thrombocytopenia, polycythemia, and neonatal mortality). Stepwise logistic
      regression was used to control for gestational age, oligohydramnios, and fetal
      growth restriction. Infants with AREDF had an increased frequency of hypoglycemia
      (odds ratio=1.7) and polycythemia (odds ratio=1.7), whereas the remaining
      neonatal outcomes were explained by gestational age and growth restriction.
      Therefore, live-born infants of preeclamptic patients with AREDF velocities,
      independent of prematurity and growth restriction, are prone to hypoglycemia and
      polycythemia.

PMID- 14691344
TI  - Intrauterine fetal death caused by pit viper venom poisoning in early pregnancy.
AB  - Poisonous snakebite is a rare complication of pregnancy. It has been suggested
      that snakebite poisoning during pregnancy may cause fetal loss. We report a case
      of intrauterine fetal death after a poisonous snakebite in the first trimester of
      pregnancy. A 29-year-old pregnant Japanese woman was admitted to hospital after
      being bitten by a pit viper on her right heel. The patient was at 10 weeks of
      gestation. In response to the bite, her right leg became extremely swollen, and
      paralysis of the right oculomotor nerve was observed. Intravenous administration
      of cepharanthine, ulinastatin, hydrocortisone sodium succinate, gabexate mesylate
      and antibiotics was started. Laboratory data suggested the presence of
      rhabdomyolysis. One week after admission, although she improved clinically and
      symptomatically, transvaginal ultrasonography revealed intrauterine fetal death.
      No vaginal bleeding was observed. A dilatation and curettage was performed. The
      patient made an uneventful recovery and was discharged from hospital 17 days
      after the snakebite. Consistent with other reports, in the first trimester
      intrauterine fetal death may especially occur when the mother has systemic
      symptoms, although its mechanism remains unclear.

PMID- 14691345
TI  - Esomeprazole 40 mg provides improved intragastric acid control as compared with
      lansoprazole 30 mg and rabeprazole 20 mg in healthy volunteers.
AB  - AIM: To compare the effects of standard-dose esomeprazole with those of standard
      doses of lansoprazole and rabeprazole on intragastric pH during repeated daily
      oral dosing in healthy volunteers. METHODS: In two standardized, randomized
      crossover studies, Helicobacter pylori negative healthy volunteers (study A: 19
      males, 5 females; study B: 13 males, 10 females) received esomeprazole 40 mg and
      either lansoprazole 30 mg (study A) or rabeprazole 20 mg (study B) orally once
      daily in the morning for 5 days. Continuous 24-hour intragastric pH recording was
      performed on day 5. RESULTS: The intragastric pH was maintained >4 for 65% (95%
      CI 59.5-71.3) of the 24-hour period with esomeprazole and for 53% of the time
      (95% CI 47.0-58.9) with lansoprazole in study A (p < 0.001). In study B, the
      proportion of time with pH >4 was 61% (95% CI 53.6-68.3) with esomeprazole versus
      45% (95% CI 37.7-52.5) with rabeprazole (p = 0.005). The 24-hour median pH and
      the proportion of volunteers with intragastric pH >4 for > or =12 h and > or =16
      h were significantly higher with esomeprazole than with either lansoprazole or
      rabeprazole. CONCLUSION: Esomeprazole 40 mg provides significantly more effective
      and more sustained gastric acid control than lansoprazole 30 mg or rabeprazole 20
      mg in healthy volunteers.

PMID- 14691346
TI  - Increased expression of cytokines and adhesion molecules in rat chronic
      esophagitis.
AB  - BACKGROUND/AIMS: Cytokines and adhesion molecules regulate many inflammatory
      processes in several gastrointestinal diseases. The dynamics of cytokines and
      adhesion molecules in reflux esophagitis are unknown in detail. We examined the
      expression and dynamics of interleukin-1beta (IL-1beta), tumor necrosis factor
      alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), macrophage
      inflammatory protein-1alpha (MIP-1alpha), MIP-2, GRO/cytokine-induced neutrophil
      chemoattractant-2alpha (CINC-2alpha), intercellular adhesion molecule-1 (ICAM-1),
      leukocyte function-associated antigen 1 (LFA-1; CD11a/CD18), and Mac-1
      (CD11b/CD18) in rat chronic reflux esophagitis. METHODS: Chronic acid reflux
      esophagitis was induced in Wistar rats by ligating the transitional region
      between the forestomach and the glandular portion and wrapping the duodenum near
      the pylorus with a small piece of an 18-Fr Nelaton catheter. Rats were killed 3
      or 21 days after operation. The levels of mRNA expression of cytokines and ICAM-1
      were determined by real-time quantitative RT-PCR. Localization of adhesion
      molecules and cytokines was investigated by immunohistochemical staining, and
      numbers of LFA-1- or Mac-1-positive cells were quantified. RESULTS: IL-1beta, TNF
      alpha, MCP-1, MIP-1alpha, MIP-2, CINC-2alpha, and ICAM-1 mRNA expression was
      significantly increased in esophageal lesions compared with normal esophagus.
      There were few these cytokines- or adhesion molecule-positive cells in normal
      esophagus. In regions of esophagitis, numerous inflammatory leukocytes in lamina
      propria and the submucosal layer exhibited positive reactions for these cytokines
      and endothelial cells were intensely stained for ICAM-1. Numbers of LFA-1- and
      Mac-1-positive cells were significantly increased in rat chronic esophagitis.
      Treatment with rabeprazole almost completely inhibited development of chronic
      acid reflux esophagitis and significantly decreased expression of cytokines and
      ICAM-1 mRNA in esophageal tissue compared with control. CONCLUSION: Cytokines and
      adhesion molecules play important roles in the pathogenesis of chronic reflux
      esophagitis in this rat model.

PMID- 14691347
TI  - Timing of fetal nucleated red blood cell count elevation in response to acute
      hypoxia.
AB  - We determined the effect of an acute episode of severe hypoxia on peripheral
      nucleated red blood cell (RBC) counts in the fetal rat. Timed pregnant rats were
      randomized to a 2-hour exposure to hypoxia (placement in a chamber containing a
      gas mixture with 9% O2 +3% CO2 + balanced N2) or to a 2-hour exposure to a sham
      chamber containing room air. Two maternal animals per group underwent cesarean
      section immediately after the 2-hour period and then 4, 12, 24, 36, 48, and 60 h
      after exposure. Fetal nucleated RBC counts were compared between groups at each
      time interval. The nucleated RBC counts were not significantly different in the
      hypoxia group until 12 h (mean +/- SEM 158.0 +/- 22.4 RBC/10 high-power fields
      vs. 90.6 +/- 11.0; p = 0.03) and 24 h (133.2 +/- 16.0 vs. 84.1 +/- 9.0; p = 0.04)
      after exposure. There were no differences between groups 36, 48, and 60 h after
      exposure. In the near-term rat fetus, acute hypoxia was associated with a delayed
      but transient increase in peripheral nucleated RBC counts.

PMID- 14691348
TI  - Exploring inflammation in hemodialysis patients: persistent and superimposed
      inflammation. A longitudinal study.
AB  - BACKGROUND: Inflammation is frequently elevated, and seems to be episodic in
      hemodialysis (HD) patients. Whether, its episodic character is due to the
      temporal variability, in periods free of clinical events, of the inflammatory
      indices or due, to the acute phase response induced by common inflammatory
      stimuli, has not been investigated yet in a longitudinal study. This study
      explores inflammation forms, characteristics and causes which are probably
      related to the high cardiovascular disease (CVD) morbidity in HD patients.
      METHODS: In 37 HD patients, high-sensitivity C-reactive protein (hs-CRP), serum
      amyloid A (SAA) and interleukin-6 (IL-6) were weekly measured for 16 consecutive
      weeks. Inflammatory clinical events, in the week before every measurement, were
      recorded. Repeated measures ANOVA were applied for statistical analysis. RESULTS:
      Fifty-one of 533 patient-weeks were positive for a clinical event. Mean +/- SD
      (range) hs-CRP was 7.01 +/- 16.06 (0.2-169) mg/l for all the weeks of the study,
      38.25 +/- 39.35 (2.1-169) mg/l for the weeks with clinical events and 3.70 +/-
      3.86 (0.2-26.1) mg/l for the weeks free of events. Variations for SAA and IL-6
      were similar. 'Clinical events' strongly influenced acute-phase proteins and IL-6
      levels. The effect of the factor 'time' (as assessed by inflammatory indices
      variation in weekly repeated measurements) was significant for all the 3 indices
      measured, independently of the factor 'clinical events'. CONCLUSIONS: In periods
      free of clinical events, microinflammation characterizes HD patients and
      fluctuates in time. Inflammation due to common clinical events is added,
      periodically, to this microinflammation. The high level persistent
      microinflammation as well as the superimposed--due to clinical events-
      inflammation could be related to the CVD in these patients.

PMID- 14691349
TI  - Endothelial cell injury markers in chronic renal failure on conservative
      treatment and continuous ambulatory peritoneal dialysis.
AB  - AIM: In chronic renal failure in dialyzed patients vascular damage is frequently
      observed and it is probable that disturbances in fibrinolytic activity and
      endothelial dysfunction may play a role in vascular complications such as stroke
      or ischemic heart disease. There have been a few data concerning hemostasis in
      chronic renal failure. Since hemostatic disturbances in nephrotic syndrome mimick
      those observed in patients maintained on chronic ambulatory peritoneal dialyses
      (CAPD), the aim of the study was to assess adhesion molecules (P-selectin, E
      selectin, ICAM, VCAM and markers of endothelial cell injury), von Willebrand
      factor, thrombomodulin, and TFPI (tissue factor pathway inhibitor) in CAPD
      patients as well as in subjects with chronic renal failure (CRF) treated
      conservatively. METHODS: The studies were performed on 23 CAPD patients, 24
      patients with nephrotic syndrome and 24 sex- and age-matched healthy volunteers.
      TFPI total, full length, truncated, von Willebrand factor, trombomodulin, P
      selectin, E-selectin, ICAM, VCAM and vascular endothelial growth factor (VEGF)
      and its receptor sFlt3 were assayed using commercially available kits. We
      evaluated also thrombin activity (thrombin-antithrombin complexes (TAT),
      prothrombin fragments 1 and 2) and the degree of plasmin generation. RESULTS: In
      CAPD and CRF patients, concentrations of the adhesion molecules P-selectin, E
      selectin, ICAM and VCAM were significantly higher when compared to the control
      group. Concentrations of total, free and truncated TFPI were significantly higher
      in CAPD and CRF patients when compared to the healthy volunteers. Concentrations
      of 'classical' markers of endothelial cell injury, von Willebrand factor and
      thrombomodulin, were significantly higher in CAPD and CRF patients when compared
      to the control group. In CAPD patients, VCAM and thrombomodulin were
      significantly elevated when compared to the CRF patients. CONCLUSIONS: The
      elevated levels of adhesion molecules in CAPD patients probably reflect
      inadequate clearance as well as enhanced synthesis/release. They may also
      indicate endothelial cell injury as well as elevated levels of von Willebrand
      factor and trombomodulin and increased ICAM and VCAM in CAPD patients. Our
      studies indicate that in renal failure patients, particularly on CAPD, there is
      evidence of endothelial cell injury and a high degree of hypercoagulation
      relative to healthy subjects. It may lead to fibrin deposition in the vascular
      wall, thrombus formation, and development and progression of atherosclerosis with
      its complications.

PMID- 14691350
TI  - Renal cyclooxygenase-2 (COX-2). Physiological, pathophysiological, and clinical
      implications.
AB  - BACKGROUND/AIMS: The role of COX-2 for renal function during renal development,
      for physiology and pathophysiology of renal diseases and the side effects of
      available COX-2 inhibitors, has gained increasing interest. We aimed therefore to
      review the respective role of renal COX-2. METHODS: Review of relevant recent
      publications in the field, and in addition of in part unpublished data obtained
      in our laboratories. RESULTS: COX-2 is 'constitutively' localized in the kidney
      i.e. in macula densa, TALH, interstitial cells, and is of utmost importance for
      normal renal development. Renal COX-2 is regulated by for example sodium and
      volume intake, angiotensin II, glucocorticoids often involving specific COX-2
      promotor response elements. COX-2 derived prostanoids are required for
      preservation of renal blood flow and glomerular filtration especially in states
      of fluid deficit, they promote natriuresis, and furthermore may stimulate renin
      secretion during low-sodium intake/loop diuretic use. Conversely, COX-2
      inhibitors decrease glomerular filtration, and renal perfusion, sometimes even
      causing acute renal failure. In addition, COX-2 inhibitors cause sodium
      retention, edema formation, cardiac failure and hypertension. The role of COX-2
      derived prostanoids in renal inflammation or failure including diabetic
      nephropathy and renal transplantation remains at present controversial.
      CONCLUSION: COX-2 is one of the major players in renal physiology and
      pathophysiology. One focus of future work should be placed on COX-2 in primary
      renal diseases.

PMID- 14691352
TI  - Defining subtypes of childhood bipolar illness.

PMID- 14691353
TI  - Next generation of preventive interventions.

PMID- 14691354
TI  - Citalopram and dystonia.

PMID- 14691355
TI  - Harry Potter and butterbeer.

PMID- 14691356
TI  - Current evolutionary perspectives on adolescent romantic relations and sexuality.
AB  - This article describes current evolutionary research on adolescent sexual and
      romantic behavior. It first reviews functional explanations for basic sex
      differences in behavior. As in other pair-bonding mammals, women seek dominant
      males, and men seek and guard young, fertile females. Recent work is then
      described on adolescent competitiveness, mate selection, and pair bonding. The
      outcomes of even childhood social competition can be profound, with healthy,
      early-maturing, attractive children deriving lifelong benefits. Adolescent
      competition is intense among girls as well as boys. Depression is more common for
      boys with few sex partners, and for girls with many. Based on cross-cultural data
      and on analysis of pubertal changes in girls and boys, it can be concluded that
      adolescents have an evolved propensity for early sexual experimentation, followed
      by more judicious mate choice. Yet the bond with a girl's first sex partner is
      often profound. Amorous infatuations are intense in both sexes and usually
      mitigate within 3 years, for plausible adaptive reasons. Early menarche and
      unmarried motherhood impose developmental disadvantages on children but may be an
      evolved adaptation for stressful family conditions and a shortage of marriageable
      men. Gaining an understanding of normal adolescence can help in diagnosing,
      preventing, and treating problematic behaviors.

PMID- 14691358
TI  - Review of child and adolescent refugee mental health.
AB  - OBJECTIVE: To review stressful experiences and stress reactions among child and
      adolescent refugees, as well as interventions and ethical considerations in
      research and clinical work, within the framework of the chronological experiences
      of child refugees; namely, the phases of preflight, flight, and resettlement.
      Highlighted are special refugee populations such as unaccompanied minors, asylum
      seekers, and former child soldiers. Pertinent medical findings are summarized.
      METHOD: The authors reviewed articles from 1990 to 2003 addressing the topics
      above. Literature was gathered from databases including PsycINFO, Medline, and
      SocioFile. Pertinent earlier papers and those from other disciplines cited in
      database-identified articles were also included. RESULTS: Child and adolescent
      refugees suffer from significant conflict-related exposures. Reactions to stress
      may be mediated by coping strategies, belief systems, and social relations.
      CONCLUSIONS: More research is needed on interventions, specifically on efficacy
      and cultural relevance. Interventions that have an impact on multiple ecological
      levels need further development and evaluation.

PMID- 14691359
TI  - Child and adolescent inpatient restraint reduction: a state initiative to promote
      strength-based care.
AB  - OBJECTIVE: To reduce the use of restraint and seclusion with children and
      adolescents in psychiatric inpatient units by promoting a preventive, strength
      based model of care. METHOD: The State Mental Health Authority used data
      analysis, quality improvement strategies, regulatory oversight, and technical
      assistance to develop and implement system change over a 22-month period. No
      changes in regulation or policy were undertaken. RESULTS: Comparative data
      collected before and after the interventions demonstrated substantial reductions
      in the use of restraint and seclusion. Child units (age 5-12) decreased from
      84.03 to 22.78 episodes per 1,000 patient days (72.9%), adolescent units from
      72.22 to 37.99 episodes (47.4%), and mixed child/adolescent units from 73.37 to
      30.08 episodes (59%). CONCLUSIONS: The use of restraint and seclusion in child
      and adolescent inpatient settings can be reduced through a systems approach,
      which may have applicability to other settings and systems.

PMID- 14691360
TI  - Cognitive-behavioral family treatment of childhood obsessive-compulsive disorder:
      a controlled trial.
AB  - OBJECTIVE: To evaluate the relative efficacy of (1) individual cognitive
      behavioral family-based therapy (CBFT); (2) group CBFT; and (3) a waitlist
      control group in the treatment of childhood obsessive-compulsive disorder (OCD).
      METHOD: This study, conducted at a university clinic in Brisbane, Australia,
      involved 77 children and adolescents with OCD who were randomized to individual
      CBFT, group CBFT, or a 4- to 6-week waitlist control condition. Children were
      assessed before and after treatment and at 3 months and 6 months following the
      completion of treatment using diagnostic interviews, symptom severity interviews,
      and self-report measures. Parental distress, family functioning, sibling
      distress, and levels of accommodation to OCD demands were also assessed. Active
      treatment involved a manualized 14-week cognitive-behavioral protocol, with
      parental and sibling components. RESULTS: By an evaluable patient analysis,
      statistically and clinically significant pretreatment-to-posttreatment change
      occurred in OCD diagnostic status and severity across both individual and group
      CBFT, with no significant differences in improvement ratings between these
      conditions. There were no significant changes across measures for the waitlist
      condition. Treatment gains were maintained up to 6 months of follow-up.
      CONCLUSIONS: Contrary to previous findings and expectations, group CBFT is as
      effective in reducing OCD symptoms for children and adolescents as individual
      treatment. Findings support the efficacy and durability of CBFT in treating
      childhood OCD.

PMID- 14691361
TI  - Clinical presentation and course of depression in youth: does onset in childhood
      differ from onset in adolescence?
AB  - OBJECTIVE: To simultaneously and prospectively compare the clinical presentation,
      course, and parental psychiatric history between children and adolescents with
      major depressive disorder. METHOD: A group of prepubertal children (n = 46) and
      postpubertal adolescents (n = 22) were assessed with structured interviews for
      psychopathology and parental psychiatric history and followed once every 2 years
      for approximately 5 years. RESULTS: With the exception of more depressive
      melancholic symptoms in the adolescents, both groups had similar depressive
      symptomatology, duration (average 17 months), severity of the index episode,
      rates of recovery (85%) and recurrence (40%), comorbid disorders, and parental
      psychiatric history. Female sex, increased guilt, prior episodes of depression,
      and parental psychopathology were associated with worse longitudinal course.
      CONCLUSIONS: In general, major depressive disorder is manifested similarly in
      children and adolescents, and both groups have a protracted clinical course and
      high family loading for psychiatric disorders.

PMID- 14691362
TI  - The Columbia Suicide Screen: validity and reliability of a screen for youth
      suicide and depression.
AB  - OBJECTIVE: This study reports on the psychometric properties of a brief, self
      administered screening questionnaire, the Columbia Suicide Screen (CSS), intended
      to identify high school students at risk for suicide. METHOD: Seventeen hundred
      twenty-nine 9th- to 12th-grade students completed the CSS and Beck Depression
      Inventory during school hours in 1991 to 1994. Three hundred fifty-six students
      who screened positively and 285, group matched on age, gender, and ethnicity, who
      screened negatively were examined on the Diagnostic Interview Schedule for
      Children (DISC), version 2.3, to assess validity. The DISC-based suicide risk
      criterion was suicidal ideation or prior suicide attempt and a DSM-III-R
      diagnosis of major depression or dysthymia or substance use. Test-retest
      reliability was assessed in a subsample of 85. RESULTS: The most balanced
      algorithm had a sensitivity of 0.75, specificity 0.83, and positive predictive
      value 16%. Suicidal ideation and prior attempt item reliabilities (kappa) were
      0.48 and 0.58, respectively. Eight-day test-retest reliability for the most
      balanced scoring algorithm was 0.32. CONCLUSIONS: The CSS demonstrated good
      sensitivity and reasonable specificity identifying students at risk for suicide.
      A second-stage evaluation would be needed to reduce the burden of low
      specificity.

PMID- 14691363
TI  - Reasons for deliberate self-harm: comparison of self-poisoners and self-cutters
      in a community sample of adolescents.
AB  - OBJECTIVE: To compare motives and premeditation between adolescent deliberate
      self-poisoners and self-cutters. METHOD: In a sample of 6,020 pupils aged 15 and
      16 years who completed a self-report questionnaire, those who had deliberately
      cut themselves in the previous year (n = 220) were compared with those who had
      taken overdoses (n = 86). RESULTS: More adolescents who took overdoses than those
      who cut themselves said that they had wanted to die (66.7% versus 40.2%, chi2 =
      14.94, p <.0001) and had wanted to find out if someone loved them (41.2% versus
      27.8%, chi2 = 4.14, p =.042). Female self-cutters were more likely than male self
      cutters to say that they had wanted to punish themselves (51.0% versus 25.0%,
      chi2 = 9.25, p =.002) and had tried to get relief from a terrible state of mind
      (77.2% versus 60.9%, chi2 = 4.78, p =.029). More self-cutters than self-poisoners
      had thought about the act of self-harm for less than an hour beforehand (50.9%
      versus 36.1%, chi2 = 5.25, p =.021). CONCLUSIONS: There are differences between
      adolescents' motives for overdoses and for self-cutting, and also gender
      differences in the reasons for self-cutting. The often impulsive nature of these
      acts (especially self-cutting) means that prevention should focus on encouraging
      alternative methods of managing distress, problem-solving, and help-seeking
      before thoughts of self-harm develop.

PMID- 14691364
TI  - Utility of TOCA-R scores during the elementary school years in identifying later
      violence among adolescent males.
AB  - OBJECTIVE: To evaluate the utility of a teacher-rating instrument (TOCA-R) of
      aggressive behavior during elementary school years in identifying boys at risk
      for later violence. METHOD: A community epidemiological sample of 415 public
      school boys was rated at six time points during elementary school regarding their
      level of aggressive/disruptive behavior. Violence was measured using juvenile
      police and court records. RESULTS: The risk for later violence varied as a
      function of the boys' level of aggressive behavior. This relationship peaked in
      third grade, where more aggressive boys compared to less aggressive boys were
      twice as likely to commit later violent acts. In respect to identifying at-risk
      boys, three intervention scenarios were compared. When minimizing false
      positives, the optimal test was found in the fall of first grade, with 83% of the
      high-risk compared to 22% of the low-risk boys later having a violent arrest
      record. When minimizing false negatives, the optimal test was found in the spring
      of fourth grade (30% of the high-risk boys versus 0% of the low-risk boys).
      Focusing on both false positives and false negatives, the optimal test was found
      in the spring of third grade (52% of the high-risk boys versus 14% of the low
      risk boys). CONCLUSIONS: Early levels of aggressive behavior are strong and
      robust predictors of later violence but are of limited utility in the early
      identification of boys at risk. Consequently, universal interventions followed by
      selected/indicated interventions based on a multistage assessment promise the
      highest utility in preventing youth violence. Future research is needed to
      identify other indicators that can strengthen the screening utility of aggressive
      behavior.

PMID- 14691365
TI  - Psychiatric disorders in a representative sample of incarcerated boys in the
      Netherlands.
AB  - OBJECTIVE: To determine the prevalence of psychiatric disorders among
      incarcerated male adolescents and to investigate the influence of psychopathology
      on allocation to either plain detention or detention with compulsory treatment.
      METHOD: A cross-sectional study of a representative sample (N = 204) of
      incarcerated boys aged 12 to 18, using the Diagnostic Interview Schedule for
      Children (DISC). Data were collected from December 1998 to December 1999.
      RESULTS: Of the eligible subjects, 79% agreed to participate. Ninety percent
      reported at least one psychiatric disorder: disruptive behavior disorder 75% (95%
      confidence interval [CI]: 68-81%), substance use disorder 55% (95% CI: 48-63%),
      psychotic symptoms 34% (95% CI: 27-41%), ADHD 8% (95% CI: 5-13%), anxiety
      disorder 9% (95% CI: 6-15%), and affective disorder 6% (95% CI: 3-10%). After
      controlling for a broad range of sociodemographic characteristics and former
      treatment parameters, the presence of a psychiatric disorder was not associated
      with allocation to compulsory treatment. CONCLUSIONS: Compared with North
      American studies, relatively low rates of anxiety and affective disorders were
      found, probably due to the better availability of mental health services to
      disadvantaged youths with internalizing problems in the Netherlands. It should be
      examined whether standardized psychiatric assessments can improve the efficiency
      of allocation to detention programs with or without psychiatric treatment
      options.

PMID- 14691366
TI  - Evidence-based thinking and the alliance with parents.

PMID- 14691369
TI  - Summary of the practice parameter for the use of electroconvulsive therapy with
      adolescents.
AB  - Electroconvulsive therapy (ECT) may be an effective treatment for adolescents
      with severe mood disorders and other Axis I psychiatric disorders when more
      conservative treatments have been unsuccessful. ECT may be considered when there
      is a lack of response to two or more trials of pharmacotherapy or when the
      severity of symptoms precludes waiting for a response to pharmacological
      treatment. The literature on ECT in adolescents, including studies and case
      reports, was reviewed and then integrated into clinically relevant guidelines for
      practitioners. Mood disorders have a high rate of response to ECT (75-100%),
      whereas psychotic disorders have a lower response rate (50-60%). Consent of the
      adolescent's legal guardian is mandatory, and the patient's consent or assent
      should be obtained. State legal guidelines and institutional guidelines must be
      followed. ECT techniques associated with the fewest adverse effects and greatest
      efficacy should be used. The presence of comorbid psychiatric disorder is not a
      contraindication. Systematic pretreatment and posttreatment evaluation, including
      symptom and cognitive assessment, is recommended.

PMID- 14691370
TI  - Summary of the practice parameter for the assessment and treatment of children
      and adolescents with enuresis.
AB  - Enuresis is a symptom that is frequently encountered in child psychiatric
      evaluations. Careful assessment is required to identify specific urologic,
      developmental, psychosocial, and sleep-related etiologies. For most children with
      enuresis, however, a specific etiology cannot be determined. Treatment then
      involves supportive approaches, conditioning with a urine alarm, or medications
      imipramine or desmopressin acetate. The psychosocial consequences of the symptom
      must be recognized and addressed with sensitivity during the evaluation and
      treatment of enuresis.

PMID- 14691371
TI  - Serotonergic agents and alcoholism treatment: a simulation.
AB  - BACKGROUND: Those with early-onset alcoholism may better respond to ondansetron
      (a 5-HT3 receptor antagonist) than to selective serotonin reuptake inhibitor
      (SSRI) treatment, whereas those with late-onset alcoholism may present the
      reverse response pattern. Johnson and colleagues proposed a model that attempts
      to explain the observed treatment response patterns of those with early and late
      alcoholism onset by focusing on the influence of a common genetic variant in the
      serotonin transporter regulatory region (5-HTTLPR) on serotonin (5-HT) and
      dopamine (DA) system function. METHODS: The present study formalizes and extends
      Johnson's descriptive model into a computer simulation consisting of differential
      equations. For each of 16 conditions defined by genotype, drinking status,
      diagnostic status, and drug treatment, data were generated by 100 simulation
      runs. RESULTS: In every condition, the S/_ genotype (S/S and S/L) had higher
      extracellular 5-HT levels than did the L/L genotype. The S/_ genotype also had
      higher rates of postsynaptic DA firing than did the L/L genotype with the
      exception of the SSRI treatment condition, where the firing rates were similar.
      Drinking generally increased levels of extracellular 5-HT, reduced rates of
      presynaptic 5-HT firing, and increased rates of postsynaptic DA firing. Drinking
      produced increases in DA activation that were greater for the L/L genotype in the
      SSRI treatment condition and for the S/_ genotype in the ondansetron treatment
      condition. CONCLUSIONS: Genotype at 5-HTTLPR may influence relative reward of
      drinking alcohol while a person is under pharmacological treatment for
      alcoholism. Alternatively, 5-HTTLPR genotype may influence pathways of alcohol
      craving. Clinical studies should examine these hypotheses.

PMID- 14691372
TI  - Identification of a retinoid receptor response element in the human aldehyde
      dehydrogenase-2 promoter.
AB  - BACKGROUND: The human aldehyde dehydrogenase-2 promoter contains sites that bind
      members of the nuclear receptor family, and one (designated FP330-3') is
      predicted to bind retinoic acid receptors. METHODS: Binding of retinoid receptors
      to the FP330-3' oligonucleotide duplex and point mutations thereof was assayed
      using electrophoretic mobility shift assays. The function of the promoter element
      was determined in transfection assays. RESULTS: Heterodimers of retinoic acid
      receptor (RAR)alpha, beta, and gamma with retinoid X receptor (RXR)alpha bound
      the FP330-3' site. Mutagenesis of the FP330-3' site suggested that either the
      upstream DR-5 or downstream DR-1 could mediate binding of RAR/RXR. FP330-3'
      oligonucleotide duplexes were not bound by in vitro translated RXR homodimers but
      weakly competed with a synthetic DR-1 oligonucleotide duplex for binding by RXR.
      A reporter construct carrying four copies of the FP330-3' element was induced by
      cotransfection of rat hepatoma cells with a construct encoding RARalpha, when the
      RAR-specific ligand AM580 was present. Each of the three RXR isoforms alpha,
      beta, and gamma stimulated the expression of reporter constructs containing the
      FP330-3' sites in a 9-cis retinoic acid-dependent fashion in cells in culture.
      This was confirmed in the case of RXRalpha using the RXR-specific ligand
      methoprene. CONCLUSION: The human aldehyde dehydrogenase-2 promoter contains a
      retinoid response element, which may contribute to regulation of the gene.

PMID- 14691373
TI  - Alpha 4 beta 2* nicotinic acetylcholine receptors modulate the effects of ethanol
      and nicotine on the acoustic startle response.
AB  - BACKGROUND: Ethanol modulates the functional activity of alpha4beta2 neuronal
      nicotinic cholinergic receptors (nAChR) when measured in vitro, but the potential
      role of alpha4beta2 nAChRs in regulating behavioral effects of ethanol is
      unknown. Recently, Tritto et al. (Tritto T, Stitzel JA, Marks MJ, Romm E, Collins
      AC (2002) Variability in response to nicotine in the LSxSS RI strains: potential
      role of polymorphisms in alpha4 and alpha6 nicotinic receptor genes.
      Pharmacogenetics 12:197-208) reported that a polymorphism (A529T) in the alpha4
      nAChR subunit gene is associated with variability in nicotine's effects on
      startle in the LSxSS recombinant inbred (RI) strains. Ethanol also alters the
      acoustic startle response. Thus, we evaluated the potential role of alpha4beta2
      nAChRs in modulating ethanol's effects on acoustic startle. METHODS: The effects
      of ethanol on acoustic startle were determined in the LSxSS RI strains. In
      addition, the effects of ethanol and nicotine were also measured in alpha4 gain
      of function and beta2 null mutant mice. The beta2 mutants do not express the
      major variant of alpha4 nAChRs, alpha4beta2. RESULTS: An association between the
      alpha4 A529T polymorphism and ethanol's effects on startle was found in the LSxSS
      RI strains; those strains that express the A529 variant of alpha4 were more
      sensitive to ethanol-induced depression of startle. The alpha4 gain of function
      mutants were more sensitive to the effects of both nicotine and ethanol and the
      beta2 null mutants were less sensitive to both drugs. CONCLUSIONS: alpha4beta2
      containing nAChRs may play important roles in modulating the effects of both
      ethanol and nicotine on the acoustic startle response. We suggest that nAChR
      subunit genes should be evaluated as potential contributors to both alcoholism
      and tobacco abuse.

PMID- 14691374
TI  - Ethanol sensitivity of recombinant homomeric and heteromeric AMPA receptor
      subunits expressed in Xenopus oocytes.
AB  - BACKGROUND: Ethanol is known to acutely inhibit AMPA receptor function, and
      sensitivity of AMPA receptors to ethanol is dependent on subunit composition in
      vivo and in vitro. A commonly used in vitro expression system for studying
      recombinant receptor subunits is the Xenopus laevis oocyte and two-electrode
      voltage-clamp electrophysiological recording. To date, ethanol sensitivity of
      injected receptor subunit complementary RNA (cRNA) has not been shown to be
      correlated with the actual expression of receptor subunits in oocytes. In this
      study, we compared ethanol sensitivity of homomeric and heteromeric AMPA receptor
      subunits microinjected into Xenopus oocytes and confirmed subunit expression in
      oocytes by immunoblot. METHODS: cRNAs coding for the "flop" type AMPA GluR1 or
      GluR3 (homomeric), GluR2/GluR3 (heteromeric combination), and GluR1/2/3
      (heteromeric combination) were microinjected in equimolar amounts of 16 to 20 ng
      into oocytes, which were studied for their sensitivity to ethanol. Oocytes
      injected with cRNA for homomeric or heteromeric subunit combinations were
      homogenized and the expressed subunits quantified with anti-GluR1, anti-GluR2,
      and anti-GluR2/3 antibodies. RESULTS: Ethanol concentrations of 10 to 500 mM
      consistently inhibited currents activated in oocytes by 200 microM kainic acid.
      The expressed homomeric GluR1 receptor and heteromeric GluR1/2/3 receptor
      combination currents showed similar sensitivity to ethanol inhibition with half
      maximal inhibition values of 170 +/- 12 mM and 176 +/- 8 mM, respectively. The
      expressed homomeric GluR3 receptor and heteromeric GluR2/3 receptor combination
      currents were differentially sensitive to ethanol inhibition with respective IC50
      values of 238 +/- 9 mM and 338 +/- 16 mM. CONCLUSION: The expressed homomeric and
      heteromeric "flop" type AMPA receptors were differentially sensitive to ethanol,
      which may in part explain differential ethanol sensitivity in native neurons.

PMID- 14691375
TI  - Intra-amygdala infusion of the NPY Y1 receptor antagonist BIBP 3226 attenuates
      operant ethanol self-administration.
AB  - BACKGROUND: Neuropeptide Y (NPY) is the most abundant and widely distributed
      peptide in the mammalian central nervous system. Evidence suggests that NPY
      transmission at Y1 receptors may regulate alcohol self-administration in rodent
      models. The purpose of the present study was to test the involvement of NPY Y1
      receptors in the amygdala in the reinforcing effects of alcohol. METHODS: Long
      Evans rats were trained to self-administer ethanol (10% v/v) vs. water on a
      concurrent FR-1 schedule of reinforcement using a sucrose fading procedure. After
      a 1 month baseline period, bilateral injector cannulae were surgically implanted
      to terminate 1 mm dorsal to the central nucleus of the amygdala. Daily (Monday
      through Friday) operant self-administration sessions were conducted for 6 months
      after surgery. Then, the effects of intra-amygdala infusion of the high-affinity
      nonpeptide NPY Y1 receptor antagonist BIBP 3226 (1, 10, or 20 microMg) were
      determined on parameters of operant alcohol self-administration. RESULTS: Intra
      amygdala administration of 10 microM or 20 microM BIBP 3226 decreased total
      alcohol-reinforced responding and dose of self-administered ethanol (g/kg)
      without significantly altering total water responses or intake compared with
      vehicle control. Response onset was unaffected. Analysis of the temporal pattern
      of ethanol- and water-reinforced responding showed that BIBP 3226 decreased
      cumulative ethanol-reinforced responding during the 30 to 60 min period of the
      sessions. Water-reinforced responses were increased by the low dose of BIBP 3226
      (1 microM) during the 50 to 60 min period. CONCLUSIONS: Results from this study
      indicate that alcohol-reinforced responding is reduced by acute blockade of NPY
      Y1 receptors in the amygdala of rats with a long-term history of alcohol self
      administration. These data are consistent with the hypothesis that alcohol self
      administration is maintained by NPY neurotransmission at Y1 receptors in the
      central nucleus of the amygdala.

PMID- 14691376
TI  - Chronic ethanol consumption by C57BL/6 mice promotes tolerance to its
      interoceptive cues and increases extracellular dopamine, an effect blocked by
      naltrexone.
AB  - BACKGROUND: C57BL/6 (B6) mice voluntarily consume ethanol. Although preingestive
      factors might be accountable, the fact that B6 mice voluntarily consume
      sufficient ethanol to set the conditions for an ethanol-deprivation effect
      suggest that post-ingestive pharmacological induced changes also occur. In this
      study, we determined the amounts of ethanol voluntarily consumed by B6 mice and
      associated blood ethanol levels (BEL), the effects of this consumption on
      extracellular dopamine (DA) and how this was altered by naltrexone, as well as on
      its interoceptive discriminative cues. METHODS: In experiment 1, the amounts of
      12% ethanol consumed at 2, 4, and 6 hr into the active phase of the circadian
      cycle and associated BEL were determined. In experiment 2, dialysate samples were
      collected for 1 hr to establish basal DA levels. Mice were then injected with
      saline or naltrexone (6 mg/kg) and given access to water and 12% ethanol or to
      water only, and samples were collected at 20-min intervals for the next 2 hr. In
      experiment 3, mice were trained to discriminate ethanol's interoceptive cues via
      operant techniques, and half were given 3 weeks access to ethanol and water, the
      other half water only. Ethanol-consuming and water control mice were again tested
      for their ability to discriminate the drug's interoceptive cues. RESULTS: Mice
      ingested nearly 6 g/kg of ethanol and attained BEL near 100 mg/100 mL by 6 hr
      into the active phase. Ethanol intake at 2-hr into the dark phase was
      approximately 2.5 g/kg, and increased DA to approximately 100% above basal
      levels. Naltrexone reduced ethanol consumption and blocked the DA increase.
      Ethanol consumption for 3 weeks attenuated its discriminative cues. CONCLUSIONS:
      B6 mice voluntarily consume sufficient ethanol (1) to produce intoxicating BEL;
      (2) to increase DA levels in nucleus accumbens, an effect blocked by naltrexone;
      and (3) to attenuate its discriminative cues.

PMID- 14691377
TI  - Altered affective modulation of the startle reflex in alcoholics with antisocial
      personality disorder.
AB  - BACKGROUND: Individual differences in neural circuitry that regulate emotional
      reactivity may be associated with alcoholism and antisocial personality disorder
      (ASPD), a common comorbid condition. The emotion-modulated startle reflex was
      used to investigate emotional reactivity among alcohol-dependent (AD) men with
      and without ASPD. METHODS: Sixty-two men were tested: (1) AD (n = 24), (2) AD
      ASPD (n = 17), and (3) non-AD, non-ASPD controls (n = 21). Participants completed
      self-report instruments and clinical interviews and had eye-blink electromyograms
      measured in response to acoustic startle probes while viewing color photographs
      rated as affectively pleasant, neutral, and unpleasant. RESULTS: Startle blink
      magnitudes were larger during unpleasant as compared with pleasant slides for
      control and AD groups, resulting in significant linear trend effects (p < 0.001)
      and nonsignificant quadratic trend effects. In contrast, AD-ASPD did not show a
      significant difference in blink magnitude during unpleasant and pleasant slides
      and did not show a significant linear valence trend or quadratic trend effect (p
      > 0.6). Subjective valence and arousal ratings of the photographs were similar
      across groups. CONCLUSIONS: Adult male alcoholics with ASPD have abnormal
      emotional responsiveness to both pleasant and unpleasant stimuli relative to
      alcoholics without ASPD and to controls.

PMID- 14691378
TI  - Neuropeptide-Y Y5 receptors modulate the onset and maintenance of operant ethanol
      self-administration.
AB  - BACKGROUND: Neuropeptide Y (NPY) is the most abundant and widely distributed
      peptide in the mammalian central nervous system and increases feeding behavior at
      NPY Y1 or Y5 receptor subtypes. Recent pharmacological and mutant mouse data
      indicate that NPY activity at its receptors can influence ethanol self
      administration, although the direction and strength of this influence are not
      clear. METHODS: Effects of the novel NPY Y5 receptor antagonist L-152,804 on the
      onset and maintenance of operant self-administration were examined in male
      C57BL/6J mice, which were trained to self-administer ethanol (10% v/v) versus
      water via the sucrose substitution method during 16 hr overnight sessions. After
      4 months of baseline responding, mice were injected with L-152,804 (0, 10, 30, or
      60 mg/kg, intraperitoneally) before operant sessions. Potential locomotor effects
      of L-152,804 and possible interaction with the sedative properties of ethanol
      also were examined. RESULTS: All three doses of L-152,804 significantly delayed
      the onset of ethanol-reinforced responding relative to vehicle injection. L
      152,804 produced no effect on the total number of ethanol- or water-reinforced
      responses per 16 hr session. However, L-152,804 selectively modulated the
      temporal distribution of ethanol-reinforced responding depending on the dose (10
      and 60 mg/kg) and time point measured in a manner consistent with blockade of
      ethanol reinforcement. Additional experiments determined that L-152,804 (10 or 60
      mg/kg) did not alter spontaneous locomotor activity or influence the sedative
      effects of ethanol (4 g/kg). CONCLUSIONS: These results indicate that blockade
      NPY Y5 receptor activity modulates the onset and maintenance of ethanol self
      administration. For this reason, NPY-Y5 receptor antagonists may be useful in
      medical management of alcohol abuse and alcoholism.

PMID- 14691379
TI  - Pain thresholds in alcohol preferring and non-preferring rats: diurnal and
      repeated trial line differences.
AB  - BACKGROUND: Studies in humans and animals suggest that those with a genetic
      predisposition toward high levels of alcohol consumption have decreased pain
      thresholds. The present study explores this association in rat lines selectively
      bred for alcohol preference or nonpreference. METHODS: 13 HAD1, 11 LAD1, 16 iP5C,
      and 16 iNP1 rats were tested in the Ugo Basile Plantar Analgesiometer and the
      IITC Tail Flick device. Five trials were conducted in each test session with one
      session per device conducted in the light and one in the dark. Trial one latency
      represents baseline latency. Decline in Latency over Repeated Trials (DLRT) was
      analyzed using linear regression. RESULTS: Testing in the Plantar Analgesiometer
      revealed no significant line differences in baseline latency (iP5C versus iNP1;
      HAD1 vs. LAD1). The alcohol preferring lines (iP5C and HAD1), however, both
      demonstrated an increase in baseline latency in the dark phase compared to the
      light phase (p < 0.05). The iNP1 line demonstrated highly significant DLRT in
      both the light phase (p < 0.001) and dark phase (p < 0.01) while the iP5C line
      demonstrated a significant DLRT only at night (p < 0.01). In the tail flick
      apparatus, the HAD1 line demonstrated a significantly increased baseline latency
      compared to the LAD1 line in both the light (p < 0.05) and dark (p < 0.01)
      phases. The HAD1 line also demonstrated a significant increase in baseline
      latency in the dark compared to the light phase (p < 0.05) and a significant DLRT
      in the light (p < 0.01) and the dark phase (p < 0.001). CONCLUSIONS: The alcohol
      preferring HAD1 line demonstrates a significantly increased baseline tail latency
      compared to the nonpreferring LAD1 line in both light and dark phases. There is a
      significant diurnal rhythm of paw and tail latency in both of the alcohol
      preferring lines (iP5C and HAD1) but not in the nonpreferring lines (iNP1 and
      LAD1). A novel finding of Decline in Latency with Repeated Trials (DLRT) was
      found in both alcohol preferring and nonpreferring lines; degree of DLRT differed
      as a function of line and circadian period.

PMID- 14691380
TI  - Association between sweet preference and paternal history of alcoholism in
      psychiatric and substance abuse patients.
AB  - BACKGROUND: The relationship between preference for stronger sweet solutions and
      propensity to excessive alcohol drinking is supported by both animal and human
      studies. This study was designed to test the hypothesis that sweet preference is
      associated with the genetic risk of alcoholism as measured by a paternal history
      of alcoholism. METHODS: Participants were 180 patients admitted to a residential
      treatment program for the treatment of alcoholism, drug dependence, or
      psychiatric conditions. In addition to a routine medical examination, patients
      completed the standard sweet preference test twice (on the 9th and 24th days
      after admission), and the family history of alcoholism was evaluated. RESULTS:
      Sweet preference was shown to be stable over time. It was strongly associated
      with a paternal history of alcoholism, with family history-positive patients
      approximately 5 times more likely to prefer stronger sweet solutions than family
      history-negative subjects. Such factors as dependence on alcohol, cocaine,
      opiates, cannabis, other drugs (including prescription drugs), and tobacco
      smoking, as well as demographics (gender and age), did not significantly
      interfere with association between sweet preference and paternal history of
      alcoholism. CONCLUSIONS: These findings provide some support for the hypothesis
      that preference for stronger sweet solutions is associated with a genetic
      predisposition to alcoholism as measured by a paternal history of alcoholism.

PMID- 14691381
TI  - Drinking to cope in socially anxious individuals: a controlled study.
AB  - BACKGROUND: Several hypotheses exist to account for the higher than normal rate
      of alcoholism in individuals with high trait anxiety (or anxiety disorders). Most
      of these suggest that the practice of drinking alcohol to reduce anxiety leads to
      an increased risk of alcoholism in vulnerable individuals. The first assumption
      of the hypothesis is that anxious individuals use alcohol to cope with their
      anxiety. Few studies have examined this issue systematically, and none have used
      a nonanxious matched control group. METHODS: Twenty-three individuals with high
      social anxiety and 23 nonsocially anxious matched controls were included in the
      study. Groups were similar on demographic variables and alcohol use. All
      participants were queried regarding the use of alcohol to cope, the practice of
      avoiding social situations if alcohol was not available, and the degree of relief
      attained by alcohol. Participants also were asked about using alcohol in 11
      specific situations. RESULTS: The socially anxious group was significantly more
      likely than controls to report using alcohol to feel more comfortable in social
      situations and to avoid social situations if alcohol was unavailable. They also
      reported a greater degree of relief of anxiety from alcohol. Exploratory analyses
      revealed that socially anxious individuals reported using alcohol more to cope
      with social interactions than with social performance situations. CONCLUSIONS:
      Individuals high in social anxiety deliberately drink alcohol to cope with their
      social fears. They report that alcohol is moderately effective at reducing their
      anxiety, which is seemingly sufficient to allow them to endure social situations.
      The data support the first assumption of the self-medication hypothesis-that
      alcohol is used to reduce social discomfort in socially anxious individuals;
      however, the study was not designed to address the veracity of the self
      medication hypothesis as a whole. Results can help guide future studies that
      examine the relationship between social anxiety and alcohol.

PMID- 14691382
TI  - The effects of affective, behavioral, and cognitive components of trait anger on
      the alcohol-aggression relation.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of affective,
      behavioral, and cognitive components of trait anger on alcohol-related aggression
      in men and women. METHODS: Subjects were 300 (150 men and 150 women) healthy
      social drinkers between 21 and 35 years of age. Trait anger was measured using
      the ABC Anger Inventory. Following the consumption of either an alcohol or a
      placebo beverage, subjects were tested on a modified version of the Taylor
      Aggression Paradigm in which mild electric shocks were received from, and
      administered to, a fictitious opponent during a competitive task. Aggressive
      behavior was operationalized as the shock intensities administered to the
      fictitious opponent under conditions of low and high provocation. RESULTS:
      Results indicated that alcohol increased aggression only for men with higher
      behavioral and cognitive anger scores and only for women with higher behavioral
      anger scores. Results also showed that when all anger components were taken into
      account, behavioral anger was the only factor that put one at risk for
      intoxicated aggression. CONCLUSIONS: Two recent studies demonstrated that the
      trait of "general" anger is a risk factor for intoxicated aggression (Giancola,
      2002a; Parrott and Zeichner, 2002). The present investigation confirmed and
      extended these findings by examining the role of three different components of
      anger. The results highlight the fact that alcohol consumption does not increase
      aggression in all persons and in all situations. An important goal for future
      research is to identify which individual difference and contextual factors are
      most important in determining who will, and will not, behave in an aggressive
      manner when intoxicated.

PMID- 14691383
TI  - Complexity changes of the EEG induced by alcohol cue exposure in alcoholics and
      social drinkers.
AB  - BACKGROUND: An understanding of the neurophysiological mechanisms underlying
      alcohol craving is important in the effective treatment of alcohol dependence.
      The aim of this study was to examine the utility of the electroencephalogram
      (EEG) to measure the changes in electrical brain activity of alcoholics when
      exposed to alcohol-specific cues. METHODS: Fifteen adult alcoholic subjects (four
      women) with a mean age of 35 (SD = 4.5) and 10 healthy social drinking controls
      (three women) with a mean age of 34 (SD = 5.6) were recruited. Subjects were
      serially rated for alcohol craving after presentations of pictures of control
      nonalcoholic and alcohol beverages. After the picture presentation, the EEG was
      recorded (16,384 data points for each epoch) with eyes closed. The dimensional
      complexity (D2) was estimated as a measure of complexity of the EEG. RESULTS:
      Alcoholic subjects exhibited a significant increase in the D2 values of the EEG
      in frontal (F3, F4), right posterior temporal (T6), and occipital (O1, O2)
      regions after viewing alcohol cues compared with viewing other beverage cues.
      These results indicate that more complex (or higher) cortical activity is induced
      over specific brain regions of alcoholic subjects by alcohol-specific cues.
      Changes in subscale of alcohol craving between nonalcoholic and alcohol pictures
      were correlated with changes in D2 values in the left frontal (F3) region in
      alcoholic subjects. CONCLUSIONS: These findings suggest that, when subjects are
      exposed to alcohol cues, changes in the EEG complexity are induced in frontal,
      right posterior temporal, and occipital areas, which may be key brain structures
      for alcohol craving. In addition, nonlinear measures like the D2 are useful in
      evaluating alcohol cue-induced brain activity from the EEG.

PMID- 14691384
TI  - Neurokinin type-3 receptor stimulation impairs ethanol-associated appetitive
      behavior in Wistar rats.
AB  - OBJECTIVES: Stimulating central neurokinin type-3 (NK-3) receptors decreases
      ethanol intake in rats. Although paraventricular nucleus of the hypothalamus
      (PVN) has a high density of NK-3 receptors, their influence on ethanol
      reinforcement has not been examined. This study's purpose was to assess the
      effects of intra-PVN infusion of senktide, a NK-3 receptor agonist, on ethanol
      self-administration. In a follow-up study, senktide's effects on ethanol self
      administration after intracerebroventricular (ICV) infusion were examined.
      METHODS: Male Wistar rats were trained to self-administer 10% ethanol (10E) in
      the "Sipper Tube" model described by Samson and colleagues, Guide cannula were
      then aimed bilaterally at the PVN or unilaterally at the lateral cerebral
      ventricle. Intra-PVN (5-100 ng/side) or ICV (30-500 ng/rat) effects of senktide
      on 10E self-administration were also examined as a preliminary test of senktide's
      selectivity. RESULTS: Intra-PVN and ICV infusion of senktide reduced the average
      number of consecutive lever presses and increased the time taken to complete the
      lever press requirement when 10E served as the reinforcer. Increased duration of
      the lever-pressing component was observed when senktide was administered prior to
      2S self-administration sessions. Neither PVN nor ICV senktide administration
      significantly altered 10E or 2S consumption. CONCLUSIONS: These data suggest that
      stimulation of central neurokinin typ-3 receptors in the Wistar rat reduces
      appetitive behavior while having little or no impact on consummatory behavior.
      Ethanol "seeking" appeared more sensitive to disruption by senktide than sucrose
      "seeking." However, further studies assessing the senktide's effects on sucrose
      maintained behavior are needed to verify this hypothesis. Lastly, it is
      hypothesized that lack of effect of senktide on intake is in part related to the
      use of outbred Wistar rats in these studies instead of selectively bred rats.

PMID- 14691385
TI  - The TWEAK is weak for alcohol screening among female Veterans Affairs
      outpatients.
AB  - BACKGROUND: The optimal brief questionnaire for alcohol screening among female
      patients has not yet been identified. This study compared the performance of the
      TWEAK (tolerance, worried, eye-opener, amnesia, cutdown), the Alcohol Use
      Disorders Identification Test (AUDIT), and the AUDIT Consumption (AUDIT-C) as
      self-administered screening tests for hazardous drinking and/or active alcohol
      abuse or dependence among female Veterans Affairs (VA) outpatients. METHODS:
      Women were included in the study if they received care at VA Puget Sound and
      completed both a self-administered survey containing the AUDIT and TWEAK
      screening questionnaires and subsequent in-person interviews with the Alcohol Use
      Disorders and Associated Disabilities Interview Schedule. Sensitivities,
      specificities, positive and negative likelihood ratios, and areas under Receiver
      Operating Characteristic curves were computed for each screening questionnaire
      compared with two interview-based comparison standards: (1) active DSM-IV alcohol
      abuse or dependence and (2) hazardous drinking and/or active DSM-IV alcohol abuse
      or dependence, the more appropriate target for primary care screening. RESULTS:
      Of 393 women who completed screening questionnaires and interviews, 39 (9.9%) met
      diagnostic criteria for alcohol abuse or dependence, and 89 (22.7%) met criteria
      for hazardous drinking or alcohol abuse or dependence. The TWEAK had relatively
      low sensitivities (0.62 and 0.44) but adequate specificities (0.86 and 0.89) for
      both interview-based comparison standards, even at its lowest cut-point (>/=1).
      The AUDIT and AUDIT-C were superior, with the following areas under the receiver
      operating characteristic curve for active alcohol abuse or dependence and
      hazardous drinking and/or active alcohol abuse or dependence, respectively:
      AUDIT, 0.90 [95% confidence interval (CI), 0.85-0.95] and 0.87 (95% CI, 0.84
      0.91); AUDIT-C, 0.91 (95% CI, 0.88-0.95) and 0.91 (95% CI, 0.88-0.94); and TWEAK,
      0.76 (95% CI, 0.66-0.86) and 0.67 (95% CI, 0.60-0.74). CONCLUSIONS: The TWEAK has
      low sensitivity as an alcohol-screening questionnaire among female VA outpatients
      and should be evaluated further before being used in other female primary care
      populations. The three-item AUDIT-C was the optimal brief alcohol-screening
      questionnaire in this study.

PMID- 14691386
TI  - Chronic ethanol consumption enhances interleukin-1-mediated signal transduction
      in rat liver and in cultured hepatocytes.
AB  - BACKGROUND: Interleukin-1 (IL-1) is a central mediator of the inflammatory
      process. Increased serum levels of IL-1 have been reported in alcoholics with
      liver damage, but it remains unknown whether chronic ethanol intake, in the
      presence or absence of lipopolysaccharide (LPS), activates IL-1 release and
      signaling in the hepatocyte. METHODS: IL-1beta and IL-10 release, expression of
      their receptors (IL-1RI and IL-10R), and the IL-1RI signal transduction response
      were evaluated in livers and cultured hepatocytes from ethanol-fed or pair-fed
      rats exposed in vivo or in vitro to LPS, ethanol, or both. RESULTS: Chronic
      ethanol intake increased both the serum levels of IL-1beta and IL-10 and the
      expression of IL-1RI, but not of IL-10R, in the liver microsomal fraction. In
      vivo LPS administration potentiated the ethanol-induced release of plasma
      cytokines. It is interesting to note that ethanol, either given in a single dose
      or chronically fed, stimulated IL-1beta and IL-10 release from cultured
      hepatocytes. Stimulation of hepatocytes with IL-1beta caused a higher activation
      of IL-1-associated kinase, extracellular receptor-activated kinases 1 and 2, and
      nuclear factor-kappaB (NF-kappaB) in hepatocytes from alcohol-fed animals than
      from controls. Furthermore, in the absence of any stimulation, hepatocytes from
      alcohol-fed animals showed an activation of both kinases, as well as an increase
      in NF-kappaB binding. Our results suggest the participation of the extracellular
      signal-regulated kinase (ERK)1/2 pathway in ethanol-induced NF-kappaB activation,
      because treatment with PD-98059, an ERK1/2 inhibitor, partially suppressed IL
      1beta-induced NF-kappaB expression. CONCLUSIONS: Chronic ethanol intake
      potentiates the action of the proinflammatory cytokine IL-1beta, enhancing the
      release and signaling response of IL-1beta in the hepatocyte, which in
      conjunction with other cytokines or LPS may exacerbate the inflammatory damage
      associated with alcoholic liver disease.

PMID- 14691387
TI  - Generation of aldehyde-derived protein modifications in ethanol-exposed heart.
AB  - BACKGROUND: Although excessive ethanol consumption is known to lead to a variety
      of adverse effects in the heart, the molecular mechanisms of such effects have
      remained poorly defined. We hypothesized that posttranslational covalent binding
      of reactive molecular species to proteins occurs in the heart in response to
      acute ethanol exposure. METHODS: The generation of protein adducts with several
      aldehydic species was examined by using monospecific antibodies against adducts
      with malondialdehyde (MDA), acetaldehyde (AA), MDA-AA hybrids, and hydroxyethyl
      radicals. Specimens of heart tissue were obtained from rats after intraperitoneal
      injections with alcohol (75 mmol/kg body weight) with or without pretreatment
      with cyanamide (0.05 mmol/kg body weight), an aldehyde dehydrogenase inhibitor.
      RESULTS: The amounts of MDA and unreduced AA adducts were found to be
      significantly increased in the heart of the rats treated with ethanol, cyanamide,
      or both, whereas no other adducts were detected in statistically significant
      quantities. Immunohistochemical studies for characterization of adduct
      distribution revealed sarcolemmal adducts of both MDA and AA in the rats treated
      with ethanol and cyanamide in addition to intracellular adducts, which were also
      present in the group treated with ethanol alone. CONCLUSIONS: These findings
      support the role of enhanced lipid peroxidation and the generation of protein
      aldehyde condensates in vivo as a result of excessive ethanol intake. These
      findings may have implications in the molecular mechanisms of cardiac dysfunction
      in alcoholics.

PMID- 14691388
TI  - Prenatal ethanol exposure modifies [3H]MK-801 binding to NMDA receptors:
      spermidine and ifenprodil.
AB  - BACKGROUND: It has been suggested that abnormalities seen in fetal alcohol
      syndrome are linked with NMDA receptor malfunction. Our laboratory has previously
      shown that prenatal ethanol treatment decreases [3H]MK-801 binding density at
      postnatal day 21, when NMDA receptor subunit protein levels were unaltered. Thus,
      the focus of the present study was to examine whether prenatal ethanol modifies
      native NMDA receptor levels. METHODS: Cerebral cortices were taken from offspring
      born to three treatment groups of pregnant Sprague Dawley(R) rats: an ethanol
      group given an ethanol liquid diet during the gestational period, a pair-fed
      control group that received a liquid diet without ethanol, and an ad libitum
      group fed rat chow and tap water. Western blot studies were carried out at
      postnatal days 1, 7, 14, and 21 to examine total protein expression of NR1 and
      NR1b splice variants. NR2 subunit levels were examined by [3H]MK-801 binding
      studies using spermidine, an endogenous polyamine, and ifenprodil, a selective
      NR2B antagonist. RESULTS: [3H]MK-801 binding density was significantly reduced in
      prenatal ethanol-treated groups compared with ad libitum and pair-fed control
      groups. Spermidine increased [3H]MK-801 binding, although potentiation by
      spermidine was not significantly different among all three experimental groups.
      Furthermore, no significant differences in total protein expression of NR1 or
      NR1b splice variants were observed in cortical membrane homogenates at postnatal
      days 1 through 21. [3H]MK-801 binding in the presence of ifenprodil showed that
      prenatal ethanol treatment significantly decreased low-affinity ifenprodil
      binding. High-affinity ifenprodil binding was reduced in both pair-fed and
      ethanol-treated groups. CONCLUSIONS: These results suggest that prenatal ethanol
      treatment reduces [3H]MK-801 binding and that this reduction may be due to a
      decrease in NR2A subunits.

PMID- 14691389
TI  - Effects of alcohol withdrawal on 24 hour ambulatory blood pressure among alcohol
      dependent patients.
AB  - BACKGROUND: Although epidemiologic studies have reported an association between
      alcohol intake and high blood pressure (BP), the results of intervention studies
      have shown inconsistent results. We embarked on a study to determine whether
      different subgroups of alcohol-dependent patients may be identified in relation
      to the effect of alcohol on BP. METHODS: Fifty alcohol-dependent men (mean age,
      41.4 years) received 0.4 g of ethanol per kilogram of body weight every 4 hr in
      200 ml of orange juice during 24 hr and the same amount of orange juice without
      ethanol during another 24 hr. Twenty-four hour ambulatory BP monitoring was
      performed during ethanol and orange juice intakes, as was hormonal and
      biochemical analysis. RESULTS: Thirty-five (75%) alcohol-dependent men were
      normotensive and 15 (30%) hypertensive. Eighteen (51%) normotensive and 12 (80%)
      hypertensive subjects showed a significant decrease in 24 hr mean BP after
      ethanol withdrawal (mean decrease of 8.4 mm Hg [95% confidence interval, -11.2 to
      -5.7] and 12.5 mm Hg [confidence interval, -16.2 to -8.8], respectively) and were
      considered as sensitive to alcohol. The remaining alcohol-dependent subjects were
      considered as resistant to alcohol. Normotensive subjects sensitive to ethanol
      showed a significantly greater left ventricular mass and a significantly lower
      ejection fraction than those normotensive patients whose BP did not change after
      ethanol withdrawal (both p < 0.01). CONCLUSIONS: More than three fourths of the
      hypertensive and more than half of the normotensive alcohol-dependent patients
      showed sensitivity to the pressor effects of ethanol. Impairment also was
      observed in heart function in normotensive patients sensitive to the pressor
      effects of ethanol.

PMID- 14691390
TI  - A mouse model of prenatal ethanol exposure using a voluntary drinking paradigm.
AB  - BACKGROUND: The incidence of fetal alcohol spectrum disorders is estimated to be
      as high as 1 in 100 births. Efforts to better understand the basis of prenatal
      ethanol-induced impairments in brain functioning, and the mechanisms by which
      ethanol produces these defects, will rely on the use of animal models of fetal
      alcohol exposure (FAE). METHODS: Using a saccharin-sweetened alcohol solution, we
      developed a free-choice, moderate alcohol access model of prenatal alcohol
      exposure. Stable drinking of a saccharin solution (0.066%) was established in
      female mice. Ethanol then was added to the saccharin in increasing concentrations
      (2%, 5%, 10% w/v) every 2 days. Water was always available, and mice consumed
      standard pellet chow. Control mice drank saccharin solution without ethanol.
      After a stable baseline of ethanol consumption (14 g/kg/day) was obtained,
      females were impregnated. Ethanol consumption continued throughout pregnancy and
      then was decreased to 0% in a step-wise fashion over a period of 6 days after
      pups were delivered. Characterization of the model included measurements of
      maternal drinking patterns, blood alcohol levels, food consumption, litter size,
      pup weight, pup retrieval times for the dams, and effects of FAE on performance
      in fear-conditioned learning and novelty exploration. RESULTS: Maternal food
      consumption, maternal care, and litter size and number were all found to be
      similar for the alcohol-exposed and saccharin control animals. FAE did not alter
      locomotor activity in an open field but did increase the time spent inspecting a
      novel object introduced into the open field. FAE mice displayed reduced
      contextual fear when trained using a delay fear conditioning procedure.
      CONCLUSIONS: The mouse model should be a useful tool in testing hypotheses about
      the neural mechanisms underlying the learning deficits present in fetal alcohol
      spectrum disorders. Moreover, a mouse prenatal ethanol model should increase the
      opportunity to use the power of genetically defined and genetically altered mouse
      populations.

PMID- 14691391
TI  - Developmental differences in the sensitivity of hippocampal GABAA receptor
      mediated IPSCS to ethanol.
AB  - BACKGROUND: Ethanol consumption by juveniles and adolescents is a public health
      problem of massive proportions. Recent studies have indicated that adolescents
      may be less sedated by ethanol than adults, and may thus be able to consume more
      ethanol, putting them at greater risk for ethanol addiction and other negative
      consequences of ethanol use. However, the mechanisms underlying this
      developmental difference are unknown. One contributing factor may be GABAA
      receptor-mediated inhibition, which is known to produce sedation. Ethanol is
      known to enhance this inhibitory process. METHODS: Using whole cell recording, we
      tested the response of GABAA receptor-mediated IPSCs in brain slices of rat
      hippocampus from animals representing three developmental stages: juvenile, early
      adolescent, and adult. RESULTS: We found significantly greater ethanol-induced
      enhancement of GABA-mediated IPSPs in cells from adult animals compared to those
      from juvenile or adolescent animals. CONCLUSIONS: We conclude that the
      sensitivity of GABAA receptor-mediated inhibitory processes to ethanol increases
      with development from the juvenile period to adulthood.

PMID- 14691392
TI  - [Trefoil factor family gene and peptide expression in pterygium].
AB  - PURPOSE: Trefoil factor family (TFF) peptides (formerly P-domain peptides;
      trefoil factor) are small (7-12 kDa) protease-resistant secreted peptides
      designated pS2 (or TFF1), SP (TFF2) and ITF (TFF3). Human conjunctival goblet
      cells (GCs) are known to synthesize TFF, but TFF expression by these cells has
      not been studied in pathological conditions. We quantified trefoil factor family
      (TFF) gene transcripts in pterygium, and we immunolocalized TFF protein. METHODS:
      Eleven pterygium specimens were studied, together with 19 biopsy specimens of
      normal human conjunctiva as controls. TFF1 (pS2), TFF2 (spasmolytic peptide) and
      TFF3 (intestinal trefoil factor) mRNA expression was semiquantified by means of
      reverse-transcription polymerase chain reaction amplification (RT-PCR). TFF1,
      TFF2 and TFF3 mRNA levels were determined individually, relative to beta2
      microglobulin housekeeping gene mRNA (internal standard), by coamplification of
      the target fragments and beta2 microglobulin in the same tube. Five pterygia and
      five normal human conjunctival biopsy specimens were also analyzed for TFF1 and
      mucin (MUC5AC) protein expression by immunostaining with monoclonal antibodies.
      Anti-PS2 (Zymed Laboratories, San Francisco), a mouse monoclonal antibody (MAb)
      against the 30 C-terminal amino acids of human TFF1, and P2802 (provided by
      Doctor Marie-Christine Rio, Institut de Genetique et de Biologie Moleculaire et
      Cellulaire, CNRS/INSERM, Strasbourg, France), a mouse MAb directed against a
      synthetic peptide corresponding to the last 28 amino acids of TFF1, were used at
      1/20 dilution. A mouse monoclonal antibody directed against the peptidic core of
      gastric M1 mucin was used as previously described. M1 immunoreactivity is encoded
      by the MUC5AC gene. RESULTS: TFF1 and TFF3 mRNA was expressed in all normal
      conjunctival and pterygium specimens. TFF2 mRNA was not expressed by either
      sample type, but was expressed by the positive control (human stomach cDNA). TFF1
      mRNA expression was stronger in pterygium than in controls (p=0.02). TFF3 mRNA
      expression was similar in the two sample types (p=0.89). TFF are coexpressed and
      act in concert with mucins to protect mucous epithelia and trigger wound-healing
      responses. Inflammation and ulceration of the gastrointestinal tract are
      associated with increased TFF expression. Conjunctival GCs secrete TFF in both
      pigs and humans. We found that TFF1 mRNA was overexpressed in pterygium relative
      to healthy conjunctiva, whereas the TFF1 immunostaining patterns were similar.
      TFF1 protein expression was confined to goblet cells. However, whereas all GCs
      were positive for MUC5AC, not all GC were labeled by anti-TFF1 mAbs in either
      normal conjunctiva or pterygium. The observed TFF1 mRNA overexpression in
      pterygium was not associated with abnormal TFF1 peptide localization. Increased
      MUC5AC protein expression would be expected in pterygium, because of increased GC
      density. Indeed, in conjunctival diseases such as dry-eye syndrome in which GC
      density is decreased, mucin secretion is also decreased. This could explain the
      increased expression of TFF1 mRNA in pterygium, although not all GCs expressed
      TFF1 protein. TFF proteins are copackaged within mucous cell granules; TFF1
      preferentially colocalizes with MUC5AC, and TFF3 with MUC2. However, we found
      some cell granules containing MUC5AC but not TFF1. The proportion of TFF1
      negative GCs was similar in pterygium and normal conjunctiva. The normal TFF3
      mRNA expression in pterygium was unexpected and suggests that only GCs involved
      in TFF1 secretion are overrepresented in this pathological tissue. TFF2 mRNA was
      undetectable in both normal conjunctiva and pterygium, possibly because of its
      copackaging in mucous cell granules and its preferential cosecretion with MUC6,
      which is not expressed in the conjunctiva. CONCLUSION: As in normal conjunctiva,
      the TFF1 and TFF3 genes are expressed by conjunctival goblet cells in pterygium,
      contrary to the TFF2 gene. Only TFF1 gene expression was elevated in pterygium
      compared to normal conjunctiva.

PMID- 14691393
TI  - [Quality of life after corneal transplantation: a retrospective study].
AB  - PURPOSE: To assess how clinical and social characteristics influence health
      related quality of life among patients who have undergone corneal
      transplantation. METHODS: Sixty-eight patients followed up for at least 1 year
      after corneal transplantation participated in this study. Data were collected on
      social status, systemic co-morbidities, ocular history, best corrected visual
      acuity, and a detailed ocular examination. Questionnaires that allowed
      calculation of VF14 and the SF36 scores were filled out for each participant
      interview. The associations between questionnaire outcomes and social status,
      ophthalmic status, and general health were evaluated using one-way analysis of
      variance and multiple stepwise linear regression. RESULTS: The mean best
      corrected visual acuity (BCVA) was significantly better in the operated eye for
      keratoconus and dystrophies than for bullous keratopathy. There is a strong
      relationship between BCVA in the operated eye and the VF14 score (beta=8.45,
      p=0.005) and also between BCVA of the contralateral eye and the VF14 score
      (beta=19.91, p<0.0001). Correlations between VF14 and SF36 were all positive
      (range r=0.29-0.49, p<0.01). CONCLUSION: This retrospective analysis provided
      strong evidence for the validity and reliability of the VF14 as an instrument for
      testing visual disabilities or satisfaction in patients who had corneal
      transplantation. Astigmatism or anisometropia did not affect VF14 and SF36
      scores. The most important factors associated with the VF14 score and SF36
      measures were the visual acuity of the operated eye as well as the contralateral
      one, including their physical function, vitality, and the patient's perception of
      mental and general health.

PMID- 14691394
TI  - [External beam radiation in treatment of subfoveal vascularized pigment
      epithelium detachment in age-related macular degeneration. Long-term results of a
      pilot study].
AB  - PURPOSE: The purpose of this study was to contribute to the evaluation of long
      term external beam radiation treatment in patients with subfoveal occult
      choroidal neovessels complicated with pigment epithelium detachment in age
      related macular degeneration. MATERIALS AND METHODS: This was a retrospective
      study of ten patients with a mean age of 75 years and a mean follow-up of 18.7
      months. External beam radiation of 14.4 Gy was administered with a daily dose of
      1.8 Gy. The efficacy of the treatment was assessed based on visual acuity, the
      size of the membrane and the persistence or not of neovascular activity. RESULTS:
      We observed stabilization of visual acuity in 44% of the cases at 6 months but
      only in 20% at 19 and 30 months. The mean initial visual acuity was measured at
      0.2 at presentation and 0.1 at the final evaluation. At the end of the study, 60%
      of patients attained the level of legal blindness; 90% of patients developed a
      disciform scar, with persistence of neovascular activity in 27% of the cases. On
      fluorescein angiography, the size of pigment epithelium detachment increased more
      than one optic disc diameter in 20% of the cases at 1 year. On the other hand, no
      radiation complication was observed. DISCUSSION: The visual and anatomical
      results of our study are similar to the natural progression of occult neovascular
      membrane. External beam radiation at a dose of 14.4 Gy did not seem to provide a
      long-term benefit in the treatment of subfoveal occult neovessels associated with
      pigment epithelium detachment.

PMID- 14691395
TI  - [Imaging the lacrimal canaliculus with 20-MHz ultrasonography: a normal diagnosis
      (Part 1)].
AB  - INTRODUCTION: High-frequency ultrasonography is used in ophthalmology with probes
      at 20, 30 and 50 MHz. The latter are used particularly for examining the anterior
      segments of the eye. The physical and acoustic parameters of the 20-MHz probes
      present an ideal compromise between resolution and penetration depth for
      examination of the lacrimal passages. These probes can be adapted to the I3
      ultrasound diagnostic device, offering a clear financial advantage. MATERIAL AND
      METHODS: During the ultrasound examination, the patient is in the supine position
      with the head back and turned away from the eye to be examined. For proper
      transmission, enough gel must be applied, so that the 20-MHz probe can easily
      navigate on the surface to be scanned. If there is no inflammation, Healon can be
      applied in the canal so that it is dilated and easier to visualize. RESULTS: In
      all patients, we were able to visualize the canaliculi in the main cross-sections
      with the ultrasound. The edge of the eyelid, the lacrimal caruncle, and the
      medial palpebral ligament can serve as landmarks in the search for the
      canaliculi. CONCLUSION: The 20-MHz probes are better adapted to visualizing the
      presaccular lacrimal passages than conventional 10-MHz probes and the 50-MHz
      biomicroscope, thus enhancing the spectrum of imaging methods.

PMID- 14691396
TI  - [High-frequency ultrasonography applied to disorders of the lacrimal canaliculi
      (Part 2)].
AB  - INTRODUCTION: Thirty patients presenting disorders of the lacrimal passages were
      examined using high-frequency ultrasonography in the hopes that this diagnostic
      tool would provide better image resolution and better reproduction quality than
      conventional 8- to 10-MHz ultrasound examination. MATERIAL AND METHODS: To carry
      out this examination, we were able to combine a 20-MHz ultrasound probe to the I3
      ultrasound diagnostic device. The patient was then positioned and the interior
      palpebral angle was filled with methylcellulose. RESULTS: In all patients, we
      succeeded in detecting the course and diameter of the lacrimal passages with
      better images than those provided by conventional ultrasound. We found that
      chronic canaliculitis was an important clinical domain for the 20-MHz ultrasound.
      Diagnosis is made easily and decisive information is provided. In all patients
      with this disorder (n=5), widening of the lacrimal passages, development of a
      diverticulum, and the presence of drusen concretions were observed. CONCLUSION:
      In our opinion, the use of high-frequency sonography as a noninvasive diagnostic
      technique is advised in cases of lacrimal passage disorders and is valuable in
      detecting chronic canaliculitis.

PMID- 14691397
TI  - [Compliance of medical treatment in primitive glaucoma open angle].
AB  - INTRODUCTION: Compliance to medical treatment expresses the patient's perception
      of the disease and the treatment prescribed by the doctors. Lack of compliance
      endangers chronic glaucoma care, which explains the importance it has been given
      these last years. The objectives of this survey were to evaluate the compliance
      of adult patients suffering from primary open angle glaucoma to discover the
      influential factors. MATERIALS AND METHODS: We conducted a survey at the
      ophthalmology clinic of Le Dantec Hospital from January 1997 to May 1998 among 31
      adults being treated for primary open angle glaucoma. An indirect evaluation of
      the patients' compliance was made on the basis of a questionnaire after
      examination of their medical files. It was deemed good, average, or bad depending
      on: regularity of the patient's visits to the doctors, regularity of the
      treatment, respect of the doctor's prescription and the prescribed times for
      taking the medicine. The Chi square independence test was used to study the
      influence of the following factors: age, sex, residence, socioeconomic status,
      duration of symptom progression, level of instruction, counseling, and treatment.
      RESULTS: The patients' mean age was 60.5 years. Compliance was deemed good for
      29% of the total cases, average for 32.3%, and bad for 38.7%. Only factors such
      as the regular visits to the doctor, the regularity of the treatment, and respect
      of the doctor's prescription and the prescribed times for taking the medicine
      were found to be influential (p<0.05). CONCLUSION: The medical treatment of
      primary open angle glaucoma, whether temporary or permanent, with a maximum of
      efficacy and a minimum of side-effects requires good compliance on the part of
      the patient. This compliance in turn requires a good doctor-patient relationship
      based on effective repeated counseling to educate patients, help them understand
      the disease, and act on the influential factors.

PMID- 14691398
TI  - [Ocular and systemic complications of homocystinuria: a report of five cases].
AB  - Homocystinuria is an autosomal recessive disorder of methionine metabolism due to
      cystathionine B-synthetase deficiency. It is the second most common inborn error
      of amino acid metabolism after phenylketonuria. In addition to the eyes, the
      skeletal, central nervous and vascular systems are usually affected by
      homocystinuria. We report two family cases of two sisters and two brothers with
      homocystinuria revealed by lenticular dislocation into the anterior chamber,
      associated with mental and growth retardation, and an isolated case of
      homocystinuria revealed by poor vision with Marfan syndrome and mental
      retardation. They all underwent surgical lensectomy with anterior vitrectomy
      under general anesthesia with anaesthesic precautions to prevent vascular
      thrombosis. Ocular complications are common in patients with homocystinuria.
      Treatment must include dietary changes to reduce the incidence of ectopia lentis
      and mental retardation. Surgical treatment with modern microsurgical techniques
      should be considered in advanced ocular manifestations of homocystinuria.

PMID- 14691399
TI  - [Sclerally fixated intraocular lens implant associated with vitrectomy: a study
      of 50 cases].
AB  - INTRODUCTION: We present a retrospective study of 50 cases of scleral fixation of
      intraocular lenses (IOLs) associated with vitrectomy. MATERIALS AND METHODS: From
      January 1996 to June 2001, 50 consecutive patients who underwent surgery with
      insertion of a sclerally fixated intraocular lens implant associated with
      vitrectomy were studied. Indications included luxated lenses due to ocular
      contusion, cataract surgery complicated by capsular rupture and luxated nucleus
      or implant into the vitreous, and replacement of anterior chamber lenses. The
      implant was sutured 2 mm behind the limbus into the scleral sulcus with 10.0
      Prolene. Vitrectomy was performed to treat pre-existing maculopathy, remove the
      lens or lens fragments luxated into the vitreous or to remove a luxated implant,
      and to provide for complete retinal examination during the operation. RESULTS:
      With a mean follow-up of 30 months, the mean postoperative visual acuity was
      20/30. For 95% of cases, final visual acuity was improved compared to
      preoperative visual acuity. No postoperative complications due to the implant
      were encountered. There were four cases of cystoid macular edema and two cases of
      retinal detachment. DISCUSSION: Despite the macula edema and retinal detachments,
      there was no loss of visual acuity compared to the preoperative state. There were
      eight cases of raised intraocular pressure; seven were controlled medically and
      one after hemi-cyclocryo-therapy. CONCLUSIONS: Scleral fixation of an IOL is a
      reliable means of correcting aphakia in the absence of capsular support and may
      be associated with a vitrectomy with very little risk.

PMID- 14691400
TI  - [Conjunctival-palpebral Kaposi's angiosarcoma: report of a case].
AB  - We describe the case of a 71-year-old man who developed classic Kaposi's sarcoma
      with conjunctival-palpebral involvement. The diagnosis was made based on clinical
      and histopathological findings. The lesions of the palpebral and conjunctival
      teguments were of a nodular tumorous aspect, their clinical particularities
      similar to other tegumental involvement. The clinical elements, histopathology,
      and pathogenesis are debated. The effects of local therapy, consisting of
      intralesional injections with alpha interferon and cryotherapy, were transient.

PMID- 14691401
TI  - [Childhood Leber hereditary optic neuropathy. A case of a 6-year-old girl with
      loss of vision].
AB  - Leber hereditary optic neuropathy, also known as hereditary optical atrophy, is
      passed on by the mother. It involves a papilledema and mostly affects young
      people. It is a mitochondrial DNA disease due to the mutation of the NADH
      dehydrogenase enzyme. Mutations are not sufficient to cause visual loss. Indeed,
      some individuals accommodate with mutations but do not express the disease. The
      heteroplasmic or homoplasmic character of the mutation among patients explains
      why they develop the disease or not even though they carry the mutation.
      Symptomatology starts with a central vision loss: a painless scotoma. The disease
      can progress either toward progressive vision loss, blindness, or spontaneous
      improvement. We report the rare case of a 6-year-old girl presenting a decline in
      central visual acuity. The genetic study revealed the presence of the G11778A
      primary mutation. The physiopathogenic mechanism, the genetic hypothesis of the
      female form, diagnostic means, and treatment options will be discussed.

PMID- 14691402
TI  - [Ocular manifestation in GAPO syndrome. Report of the first tunisian case].
AB  - GAPO syndrome is a rare autosomal recessive disorder whose main manifestations
      are: growth retardation, alopecia, pseudoanodontia and optic atrophy. We report
      here the ophthalmological findings in a 12-year-old Tunisian boy suffering from
      typical GAPO syndrome.

PMID- 14691403
TI  - [Orbital location of Kaposi's sarcoma].
AB  - Kaposi's sarcoma is a proliferative disease, probably induced by human herpes
      virus type 8 (HHV8). Its expression is cutaneous and visceral, with four clinical
      forms. An orbital location of Kaposi's sarcoma remains exceptional. In order to
      evaluate the epidemiological, clinical, and therapeutic objectives of this tumor
      location, we report a case of a 58-year-old patient hospitalized in the
      ophthalmology department for a surgically treated right orbital tumor.

PMID- 14691404
TI  - [Anterior lenticonus: diagnostic aid in Alport syndrome].
AB  - Anterior lenticonus is a rare condition in which the lens presents a conical
      protrusion of its anterior cortex. Sometimes isolated, it may be an ocular
      manifestation of Alport syndrome, a hereditary nephritis accompanied by deafness
      and other ocular signs such as flecked retinopathy or posterior polymorphous
      corneal dystrophy. All these manifestations are a result of a genetic defect in
      type IV collagen, a major component of basal membranes in the human body. The
      clinical aspects and therapy of anterior lenticonus and Alport syndrome are
      described, as well as the exploration that must begin when anterior lenticonus is
      discovered. This exploration is essential so that this diagnosis can be made as
      soon as possible.

PMID- 14691406
TI  - [Conjunctival pyogenic granuloma in a patient with chalazions].
AB  - A 28-year-old male patient had a chalazion on his left eyelid. Increased
      discomfort led to the discovery of a conjunctival mass under the inner part of
      his upper eyelid. On clinical examination, a small reddish mass on the palpebral
      conjunctiva of the upper left eyelid was only visible on the underside of the
      lid; the mass was diffusely reddish. Additionally, a chalazion was present in the
      middle of the lower left eyelid. As this condition was a source of discomfort to
      the patient, the mass was surgically resected. The histological study found a
      typical pyogenic granuloma, a possible complication in the course of a chalazion.

PMID- 14691407
TI  - [Centenary of the first radiotherapy treatment of retinoblastoma (Hilgartner,
      1903)].
AB  - One hundred years ago, Hilgartner used external radiotherapy for the first time
      in the treatment of retinoblastoma. This first case was published in the Texas
      Medical Journal in 1903. Immediate results were reported to be excellent but the
      long-term outcome was not known. The first documented cure of retinoblastoma over
      a long period of time was a case initially treated by Verhoeff (Boston) in 1917,
      with histopathological findings provided 71 years later by Marcus et al. at the
      patient's death. Henry Louis Hilgartner was born in 1868 in Baltimore and died in
      1937 at the age of 69. His revolutionary treatment developed from the discovery
      of X-rays in 1895 by Wilhelm Conrad Rontgen and the parallel discovery of
      radioactivity by Henri Bequerel and Marie and Pierre Curie. In the sociopolitical
      context of 1903, Emile Loubet was president of France and this same year saw the
      Wright brothers' first motorized flight with the first power-driven heavier-than
      air machine. The development of radiotherapy in the treatment of retinoblastoma
      can be divided into three distinct periods: an initial period of trial and error
      lasting from 1903 to 1928; a second period from 1929 to 1948 covering the
      introduction of calibrated radon needles up to the advent of external
      radiotherapy, and a third period, from 1948 to the present day, which can be
      considered a time of technical improvement and innovation. One hundred years ago,
      radiotherapy made a triumphant entry on the scene of retinoblastoma management.
      With our present knowledge of its side effects, we are now trying to remove it.

PMID- 14691408
TI  - Alfuzosin (uroxatral)--another alpha1-blocker for benign prostatic hyperplasia.

PMID- 14691409
TI  - Drug interactions with grapefruit juice.

PMID- 14691411
TI  - Access site for cardiac catheterization.

PMID- 14691412
TI  - Periprocedural thromboprophylaxis in patients receiving chronic anticoagulation
      therapy.
AB  - Patients receiving chronic anticoagulation therapy pose a clinical challenge when
      therapy needs to be interrupted for surgical or invasive procedures. Maintaining
      anticoagulation places them at risk for serious bleeding complications, whereas
      discontinuing anticoagulation puts them at risk of thromboembolic complications.
      Most patients can undergo dental procedures, cataract surgery, and diagnostic
      endoscopy without discontinuing anticoagulation. The main patient groups that may
      require a periprocedural alternative to oral anticoagulation (periprocedural
      thromboprophylaxis or bridging) include patients with prosthetic heart valves,
      atrial fibrillation, and hypercoagulable states and patients with chronic venous
      thrombosis who are undergoing surgery. Currently, there is little consensus on
      the appropriate perioperative treatment of patients on long-term warfarin
      therapy. There are an increasing number of studies that evaluate the benefits of
      periprocedural bridging with low-molecular-weight heparin (LMWH) in place of
      unfractionated heparin (UFH). An advantage of LMWH over UFH is that perioperative
      conversion from warfarin therapy with LMWH can be carried out in the outpatient
      setting, which is more convenient for patients and is cost effective. As with the
      use of UFH, there are reports of maternal thromboembolic complications with LMWHs
      in pregnant women with mechanical heart valves. This review brings together the
      available data on periprocedural bridging to assess the available options for
      patients on long-term warfarin therapy who are undergoing surgical procedures. It
      provides a rationale for using LMWHs while individualizing the risks versus
      benefits in a given patient population.

PMID- 14691413
TI  - Randomized trial of Rotational Atherectomy Versus Balloon Angioplasty for Diffuse
      In-stent Restenosis (ROSTER).
AB  - BACKGROUND: Various autopsy and intravascular ultrasound (IVUS) studies have
      shown neointimal proliferation as the main mechanism of in-stent restenosis (ISR)
      responsible for >95% of luminal narrowing while stent struts are not compressed.
      ISR of diffuse type has a high incidence of recurrence (up to 70%) after balloon
      angioplasty (PTCA). Tissue ablation with percutaneous rotational coronary
      atherectomy (PRCA) may be more efficacious compared to tissue compression or
      extrusion after PTCA for the interventional treatment of diffuse ISR. METHODS:
      The Rotational Atherectomy Versus Balloon Angioplasty for Diffuse In-Stent
      Restenosis (ROSTER) trial is a single-center, randomized trial comparing PRCA to
      PTCA (both with IVUS guidance) in the treatment of diffuse ISR in 200 patients.
      In the PRCA group (n = 100), rotablation was performed using a burr-to-artery
      ratio >0.7 followed by adjunctive balloon dilatation at low pressure (4-6 atm).
      In the PTCA group (n = 100), high-pressure (>12 atm) balloon dilatation was
      performed using an optimal size balloon. The study's primary end point was target
      lesion revascularization (TLR) at 9 months and secondary end points included
      clinical events at 1 year and angiographic restenosis in a substudy of the last
      75 patients enrolled. RESULTS: Baseline clinical and angiographic variables were
      comparable between the 2 groups with similar procedural and angiographic success,
      but a higher rate of repeat stenting occurred in the PTCA group (31% vs 10%; P
      <.001). Although the angiographic acute luminal gain was similar between the 2
      groups, IVUS analysis revealed lower residual intimal hyperplasia area after PRCA
      versus PTCA (2.1 +/- 0.9 mm2 vs. 3.3 +/- 1.8 mm2; P =.005). At a mean follow-up
      of 12 +/- 2 months, there were 2 deaths, 3 myocardial infarctions, and 3 coronary
      artery bypass graft procedures in each group. TLR incidence was 32% in the PRCA
      group and 45% in the PTCA group (P =.042), with a similar trend noted in the
      angiographic substudy. CONCLUSION: The ROSTER trial for diffuse ISR revealed both
      PRCA and PTCA to be safe and effective, but PRCA resulted in less residual
      intimal hyperplasia, lower repeat stent use, and decreased TLR.

PMID- 14691414
TI  - Exploring options for improving healthcare.
AB  - New medical technologies generally must receive clearance or approval for
      marketing by the US Food and Drug Administration and be covered by an insurer,
      such as the Centers for Medicare and Medicaid Services, before becoming available
      for widespread clinical use. These 2 approval processes are discrete and usually
      occur sequentially rather than collaboratively and simultaneously. To explore
      potential mechanisms for increasing regulatory collaboration between these 2 key
      health care agencies, the Duke Clinical Research Institute and Health Strategies
      Consultancy convened an informal meeting of agency, academic, and industry
      leaders on December 8 and 9, 2002, titled "Registration/Approval and
      Coverage/Payment: Exploring Options for Improving Healthcare." This article
      arises from the discussion at this conference; it does not represent the official
      views of any person or institution involved. Although the group did not attempt
      to reach a consensus, it examined several important issues surrounding this
      regulatory debate. Herein are proposed options for enhancing regulatory
      efficiency through greater coordination between the FDA and CMS, and discussion
      of these proposals from the perspectives of members of both agencies, members of
      stakeholder organizations, and academic observers.

PMID- 14691415
TI  - Triple antiplatelet therapy does not increase femoral access bleeding with
      vascular closure devices.
AB  - BACKGROUND: The use of arteriotomy closure devices (CDs) to achieve hemostasis
      after femoral artery access in percutaneous coronary intervention is steadily
      increasing. However, the safety information with these devices in the era of
      triple antiplatelet therapy is limited. METHODS: We reviewed prospectively
      collected data from the Do Tirofiban and ReoPro Give Similar Efficacy Outcomes
      Trial (TARGET), where all patients received aspirin, clopidogrel, and
      glycoprotein IIb/IIIa inhibitor therapy. At the treating physician's discretion,
      manual compression (MC) or a vascular hemostasis device was selected following
      femoral angiography. Patients receiving MC were to have sheaths removed 2 to 6
      hours postprocedure when the activated clotting time was < or = 175 seconds.
      RESULTS: Of 4809 patients, 4736 had femoral access, and 985 of these had a CD
      (Perclose 47%, Angio-Seal 43%, VasoSeal 5%, and other 5%). The MC and CD groups
      were similar regarding most demographic characteristics, including age, systolic
      blood pressure, and weight, but those with MC were more often female, diabetic,
      and had history of peripheral vascular disease. Patients with a CD had a lower
      ischemic event rate suggesting they were a lower risk cohort overall. There were
      no differences in major bleeding at the access site (0.4% vs 0.5%, P =.588),
      minor bleeding at the access site (1.9% vs. 3.1%, P =.142) or transfusions (0.8%
      vs 1.0%, P =.513) between the MC and CD groups, respectively. CONCLUSIONS: In
      contemporary percutaneous coronary intervention practice, with appropriate
      patient selection, a CD can be safely utilized despite aggressive polypharmacy
      for procedural anticoagulation.

PMID- 14691416
TI  - Patients with chest pain calling 9-1-1 or self-transporting to reach definitive
      care: which mode is quicker?
AB  - OBJECTIVE: We examined differences in transport times for patients with chest
      pain who used private transportation compared with patients who used emergency
      medical services (EMS) to reach definitive medical care. METHODS: This was a
      retrospective cohort study with data used from the Rapid Early Action for
      Coronary Treatment (REACT) trial conducted in 20 US cities. Elapsed time to care
      was examined through the use of (1) decision to seek care to initial care
      (emergency department [ED] arrival versus EMS arrival on scene [n=1209]); (2)
      decision to ED arrival (for both groups [n=2388]); (3) time to thrombolytic
      therapy once admitted to the ED (for both groups [n=309]); and (4) decision to
      seek care to thrombolytic therapy (n=276). Elapsed travel times were ranked
      within Zip Codes and submitted to a nested analysis of variance model to
      determine if elapsed times were different between modes of transport. RESULTS:
      Private transportation (35 minutes) resulted in faster ED arrival than using EMS
      (39 minutes, P =.0014). However, if one considers EMS treatment to be initial
      care, calling 9-1-1 (6 minutes) resulted in much quicker care than patients using
      private transportation to the ED (32 minutes, P <.001). Transport by EMS resulted
      in a shorter elapsed time to thrombolytic administration compared with patients
      using private transportation when considering ED "door-to-needle" time (32 vs 49
      minutes, respectively [P <.001]) or time from decision to seek care until
      administration of thrombolytic therapy (75 vs 92 minutes, respectively, [P
      =.042]). CONCLUSIONS: Although private transportation results in a faster trip to
      the ED, quicker care is obtained with the use of EMS.

PMID- 14691417
TI  - Elevated leukocyte count and adverse hospital events in patients with acute
      coronary syndromes: findings from the Global Registry of Acute Coronary Events
      (GRACE).
AB  - OBJECTIVE: To examine the association between elevated leukocyte count and
      hospital mortality and heart failure in patients enrolled in the multinational,
      observational Global Registry of Acute Coronary Events (GRACE). BACKGROUND:
      Elevated leukocyte count is associated with adverse hospital outcomes in patients
      presenting with acute myocardial infarction (AMI). The association of this
      prognostic factor with hospital mortality and heart failure in patients with
      other acute coronary syndromes (ACS) is unclear. METHODS: We examined the
      association between admission leukocyte count and hospital mortality and heart
      failure in 8269 patients presenting with an ACS. This association was examined
      separately in patients with ST-segment elevation AMI, non-ST-segment elevation
      AMI, and unstable angina. Leukocyte count was divided into 4 mutually exclusive
      groups (Q): Q1 <6000, Q2 = 6000-9999, Q3 = 10,000-11,999, Q4 >12,000. Multiple
      logistic regression analysis was performed to examine the association between
      elevated leukocyte count and hospital events while accounting for the
      simultaneous effect of several potentially confounding variables. RESULTS:
      Increasing leukocyte count was significantly associated with hospital death
      (adjusted odds ratio [OR] 2.8, 95% CI 2.1-3.6 for Q4 compared to Q2 [normal
      range]) and heart failure (OR 2.7, 95% CI 2.2-3.4) for patients presenting with
      ACS. This association was seen in patients with ST-segment elevation AMI (OR for
      hospital death 3.2, 95% CI 2.1-4.7; OR for heart failure 2.4, 95% CI 1.8-3.3),
      non-ST-segment elevation AMI (OR for hospital death 1.9, 95% CI 1.2-3.0; OR for
      heart failure 1.7, 95% CI 1.1-2.5), or unstable angina (OR for hospital death
      2.8, 95% CI 1.4-5.5; OR for heart failure 2.0, 95% CI 0.9-4.4). CONCLUSION: In
      men and women of all ages with the spectrum of ACS, initial leukocyte count is an
      independent predictor of hospital death and the development of heart failure.

PMID- 14691418
TI  - Predictors of exercise capacity and the impact of angiographic coronary artery
      disease in heart transplant recipients.
AB  - BACKGROUND: Maximal exercise capacity is limited in patients after heart
      transplantation. The extent to which transplant coronary artery disease
      contributes to exercise intolerance in these patients has not been well defined.
      METHODS: This prospective study examined exercise capacity among 174 heart
      transplant recipients who underwent 358 exercise tests 0.3 to 13 years after
      surgery. Data were collected as part of routine posttransplantation treatment
      that each year consist of clinical and hemodynamic measurements (including
      ejection fraction, cardiac index, pulmonary capillary wedge pressure, and the
      presence of coronary artery disease) and cardiopulmonary exercise test (including
      measures of peak VO2). The mean follow-up was 3.5 +/- 0.2 years after
      transplantation. Serial exercise test data were available in 102 patients
      RESULTS: Peak VO2 was 19.4 +/- 0.4 mL/kg per minute, representing 70% +/- 1.3% of
      the age-predicted value. Exercise capacity increased significantly after
      transplantation and then remained stable throughout long-term follow-up. Only
      age, maximal systolic blood pressure, pulmonary vascular resistance, and body
      mass index were independent determinants of exercise capacity (R2 = 0.51),
      whereas specific transplant factors such as denervation, hemodynamic variables,
      donor characteristics, immunosuppressive drugs, biochemical parameters, and
      transplant coronary artery disease (TxCAD) did not contribute to the explanation
      of reduced exercise capacity. Although TxCAD was not related to exercise capacity
      in the multivariate analysis, exercise capacity declined by 17.1% (P <.05) among
      those in whom CAD developed during follow-up. CONCLUSIONS: Exercise capacity is
      reduced among heart transplant recipients, and age is the strongest determinant
      of aerobic performance. Specific transplant-related factors, including TxCAD, do
      not contribute significantly to the explanation of exercise capacity. However,
      the occurrence of TxCAD may contribute to reduced exercise capacity during follow
      up, since peak VO2 appears to decline only among those who have TxCAD.

PMID- 14691419
TI  - Acute myocardial infarction in patients infected with human immunodeficiency
      virus.
AB  - BACKGROUND: Recent clinical and post-mortem reports suggests that human
      immunodeficiency virus (HIV) infection may participate in the process of
      atherosclerosis independent of other coronary risk factors. In this prospective
      and observational study, we investigated whether an associative link exists
      between HIV infection and coronary artery disease. METHODS: Of 690 patients
      admitted to our hospital in a 3-year period, 29 patients (28 men and 1 woman)
      with a mean age of 46 +/- 10 years had an acute myocardial infarction (AMI) on
      the basis of acute prolonged chest pain, ischemic electrocardiogram
      abnormalities, and elevated serum markers of myocardial necrosis at presentation.
      RESULTS: ST-segment elevation MI was present in 15 patients, and non-ST-segment
      elevation MI was present in 14 patients. Twenty-two patients (76%) were <55
      years; 17 of these patients had no or 1 coronary risk factor, and 5 patients had
      2 or 3 risk factors. Five patients >55 years had 1 coronary risk factor, and 2
      patients had 2 risk factors. Thirteen patients underwent a myocardial
      revascularization procedure, and 1 patient died during hospitalization.
      CONCLUSIONS: HIV infection, as a cause of endothelial injury, may initiate the
      inflammatory process of early atherosclerosis and participate in the evolution of
      the atherothrombotic lesion responsible for AMI. This study suggests that the
      association of HIV infection and acute coronary syndrome may be more common than
      previously reported and underscores the need for further clinical studies.

PMID- 14691420
TI  - Brain natriuretic peptide predicts right heart failure in patients with acute
      pulmonary embolism.
AB  - BACKGROUND: Plasma levels of brain natriuretic peptide (BNP) are increased in
      patients with left heart failure. In patients with severe pulmonary embolism
      (PE), primary right ventricular (RV) dysfunction is frequent. Little is known
      about BNP secretion in acute RV failure. METHODS: We prospectively studied 50
      consecutive patients with confirmed PE (age range, 57 +/- 19 years; 36 men). PE
      was confirmed with pulmonary angiography, spiral computed tomography, or
      echocardiography and subsidiary analyses. On admission, echocardiography and BNP
      measurements were performed in all patients. RESULTS: Patients without RV
      dysfunction had significantly lower BNP levels than patients with RV dysfunction
      (55 +/- 69 pg/mL vs 340 +/- 362 pg/mL, P <.001). There was a significant
      correlation between RV end-diastolic diameter and BNP (r = 0.43, P <.05). BNP
      discriminated patients with or without RV dysfunction (area under the receiver
      operating characteristic curve, 0.78; 95% CI, 0.64-0.92). A BNP >90 pg/mL was
      associated with a risk ratio of 28.4 (95% CI, 3.22-251.12) for the diagnosis of
      RV dysfunction. All patients without LV systolic dysfunction who had syncope
      necessitating cardiopulmonary resuscitation had normal BNP levels. Patients with
      RV dysfunction had significantly more in-hospital complications (cardiogenic
      shock, inotropic therapy, mechanical ventilation). However, BNP levels were not
      predictive of mortality or in-hospital complications. CONCLUSIONS: BNP levels are
      frequently increased in patients with PE who have RV dysfunction, whereas
      patients without RV dysfunction show reference range BNP levels in the absence of
      left ventricular dysfunction. In acute PE, BNP elevation is highly predictive of
      RV dysfunction, but not of in-hospital complications and mortality.

PMID- 14691421
TI  - Predictors of cardiologist care for older patients hospitalized for heart
      failure.
AB  - BACKGROUND: Studies have suggested that cardiologists may provide higher quality
      heart failure care than generalists. However, national rates of specialty care
      during hospitalization for heart failure and factors associated with care by a
      cardiologist are unknown. METHODS: We assessed specialty care in a sample of
      Medicare patients hospitalized nationwide with heart failure between 1998 and
      1999 (n = 25,869). Multivariable hierarchical logistic regression models were
      used to identify factors independently associated with treatment by a
      cardiologist. RESULTS: One-quarter (25.5%) of patients had a cardiologist as
      their attending physician, 31.3% of patients received a cardiology consult, and
      43.2% of patients were not treated by a cardiologist during hospitalization.
      Older patients (age <75 years: referent; age 75-84 years: risk ratio [RR], 0.92;
      95% CI, 0.86-0.98; age > or =85 years: RR, 0.81; 95% CI, 0.74-0.88) and women
      (RR, 0.87; 95% CI, 0.83-0.93) were less likely to have an attending cardiologist.
      Patients with a history of heart failure (RR, 1.13; 95% CI, 1.06-1.20), coronary
      disease (RR, 1.23; 95% CI, 1.14-1.32), coronary artery bypass grafting (RR, 1.42;
      95% CI, 1.32-1.42), or percutaneous transluminal coronary angioplasty (RR, 1.30;
      95% CI, 1.19-1.42) were more likely to be treated by a cardiologist, whereas
      patients with chronic obstructive pulmonary disease (RR, 0.74; 95% CI, 0.70-0.79)
      and dementia (RR, 0.61; 95% CI, 0.54-0.70) were less likely to be treated by a
      cardiologist. Patient race was not associated with treatment by a cardiologist.
      The strongest predictors of attending cardiology care were hospital factors,
      including large volume (>300 beds; RR, 1.45; 95% CI, 1.32-1.42) and geographic
      location (RR, 1.00 Northeast (referent) vs RR, 0.55; 95% CI 0.46-0.65 Midwest).
      CONCLUSIONS: Slightly more than half of older patients with heart failure
      received care from a cardiologist. Several patient characteristics, including age
      and sex, were associated with the use of specialty care, suggesting that factors
      other than clinical presentation may independently influence the use of specialty
      care.

PMID- 14691422
TI  - The expanding national burden of heart failure in the United States: the
      influence of heart failure in women.
AB  - BACKGROUND: Although some studies have shown that hospital admissions for heart
      failure doubled between 1973 and 1995, other data suggest that the heart failure
      hospitalization epidemic has stabilized in the United States. We sought to
      describe trends in heart failure hospitalizations over the past decade using data
      from the National Hospital Discharge Survey (NHDS). METHODS: The NHDS provides
      annual estimates of hospitalization discharges from a sample of hospitals in the
      United States. We combined the heart failure hospitalization frequencies with
      census estimates to calculate age and gender-specific annual hospitalization
      rates. RESULTS: Hospitalizations with a primary diagnosis of heart failure among
      adults (age > or =35) increased from 810,624 in 1990 to 989,500 in 1995 (annual
      increase 36,088, R2 = 0.816, P =.014), and to 1,088,349 in 1999 (annual increase
      31,091, R2 = 0.780, P =.047). The age-adjusted hospitalization rate (per 1000
      persons) increased from 7.186 in 1990 to 8.554 in 1999 for women (annual increase
      0.14/year, R2 = 0.731, P =.002) and from 6.892 in 1990 to 7.372 in 1999 for men
      (annual increase 0.011/year, R2 = 0.008, P = 0.80). For women, the annual
      hospitalization rate increased from 1990 to 1999 in each age group (35-64, 65-74,
      75-84, and > or =85), while the age-specific rates did not change in men.
      CONCLUSIONS: Heart failure hospitalizations have continued to increase from 1990
      to 1999. Although aging and growth of the US population contribute to this trend,
      the increases are substantially influenced by changes in hospitalization rates in
      women.

PMID- 14691423
TI  - Patterns of beta-blocker utilization in patients with chronic heart failure:
      experience from a specialized outpatient heart failure clinic.
AB  - BACKGROUND: Beta-blockers have been shown incontrovertibly to improve morbidity
      and survival in patients with heart failure. However, there is limited
      information regarding their use in clinical practice settings, and reasonable
      utilization targets for quality improvement initiatives have not been
      established. METHOD: We identified 500 consecutive patients with chronic heart
      failure seen at a specialized outpatient heart failure clinic from March 2001 to
      May 2001, and retrospectively extracted clinical and drug information from an
      electronic medical record. RESULTS: In this cross-sectional analysis, the rate of
      beta-blocker utilization was 69%. Seventy-five percent of patients had at least
      tried a beta-blocker. Among those with beta-blockers initiated, 16% experienced
      side effects that led to drug discontinuation (9.1%) or down-titration (6.9%)
      that was similar across all NYHA classes. A lower utilization rate of beta
      blockers was observed in patients of advanced age and those with diabetes
      mellitus, concomitant antiarrhythmic therapy, and preserved left ventricular
      ejection fraction (P <.05). Respiratory disease remained the most common reason
      for withholding beta-blocker therapy, especially with severe obstructive (rather
      than restrictive) physiology. CONCLUSION: It appears that about 70% of patients
      with chronic heart failure can be successfully treated with a beta-blocker in a
      specialized heart failure outpatient setting where physicians are committed to
      beta-blocker use in heart failure. It is possible that subgroups with lower
      utilization rates can be targeted for quality improvement initiatives.

PMID- 14691424
TI  - Evaluating the benefits of glycoprotein IIb/IIIa inhibitors in heart failure at
      baseline in acute coronary syndromes.
AB  - BACKGROUND: We evaluated whether the use of glycoprotein IIb/IIIa receptor
      inhibitors, in addition to heparin and aspirin, imparts an incremental benefit in
      a subgroup of patients with acute coronary syndromes (ACS) who had congestive
      heart failure (CHF) symptoms at presentation. METHODS: We analyzed patients
      enrolled in the Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using
      Integrilin Therapy (PURSUIT) trial, a randomized, double-blind, placebo
      controlled study evaluating the use of eptifibatide versus placebo for patients
      with ACS without persistent ST-elevation. We compared the clinical
      characteristics and 30-day outcomes for 861 patients who had Killip class II or
      III CHF symptoms with those of 8558 patients who had no CHF symptoms. RESULTS:
      Odds ratios for the primary end point, 30-day death or non-fatal myocardial
      infarction, in the placebo group versus the eptifibatide group were similar for
      patients with and without CHF (odds ratio, 1.11; 95% CI, 0.8-1.5; odds ratio,
      1.13; 95% CI, 1.0-1.3). However, adverse events were almost twice as frequent for
      patients with CHF compared with patients with no CHF (24.5% vs 14%). CONCLUSIONS:
      Although patients with non-ST-segment elevation ACS who have CHF have markedly
      worse outcomes than patients without CHF symptoms, we did not find an incremental
      benefit from the use of eptifibatide in this seriously ill subgroup.

PMID- 14691425
TI  - Microvascular alterations in patients with acute severe heart failure and
      cardiogenic shock.
AB  - BACKGROUND: Microvascular blood flow alterations may impair tissue oxygenation
      and may participate in the development of multiple organ failure in patients with
      severe heart failure. We hypothesized that microvascular blood flow alterations
      are present in patients with severe heart failure and cardiogenic shock. METHODS:
      We used an orthogonal polarization spectral imaging technique to investigate the
      sublingual microcirculation in 40 patients with acute severe heart failure,
      including 31 patients with cardiogenic shock, and in a control group of 15
      patients who were examined the day before cardiac surgery. The effects of topical
      application of acetylcholine (10-2M) were also tested in 5 patients with
      cardiogenic shock. Five sublingual areas were recorded, allocated a random
      number, and later analyzed semiquantitatively. Data were analyzed with non
      parametric tests and presented as medians (percentiles 25-75). RESULTS: The
      density of all the vessels was similar in the 3 groups. The proportion of
      perfused small (<20 microm) vessels was lower in patients with cardiac failure
      and cardiogenic shock than in control patients (63% [46%-65%] and 49% [38%-64%]
      vs 92% [90%-93%], P <.001). The perfusion of large vessels was preserved in all
      groups. The proportion of perfused vessels was higher in patients who survived
      than in patients who did not survive in all vessels (90% [84%-93%] vs 81% [74%
      87%], P <.05) and in small vessels (64% [49%-68%] vs 43% [37%-62%], P <.05). The
      topical application of acetylcholine totally reversed these alterations
      CONCLUSIONS: Microvascular blood flow alterations are frequently observed in
      patients with severe heart failure and are more severe in patients who do not
      survive.

PMID- 14691426
TI  - Change in circulating cytokines after 2 forms of exercise training in chronic
      stable heart failure.
AB  - BACKGROUND: A proinflammatory state is recognized in chronic heart failure and
      the degree of immune activation corresponds to disease severity and prognosis.
      Training is known to improve symptoms in heart failure but less is known about
      the effects of specific forms of training on the proinflammatory state. METHODS:
      Forty-six patients with stable chronic heart failure underwent a home-based
      program of exercise training for 30 minutes a day, 5 days per week over a 6-week
      period. Twenty-four used a bicycle ergometer and 22 used an electrical muscle
      stimulator applied to quadriceps and gastrocnemius muscles. Tumour necrosis
      factor-alpha (TNF-alpha), TNF-alpha soluble receptors 1 and 2, interleukin 6, and
      C-reactive protein were measured before and after the training period. RESULTS:
      Significant improvements in markers of exercise performance were seen in both
      training groups. Soluble TNF-alpha receptor 2 levels decreased after training in
      the bike group only (2900 +/- 1069 pg/mL to 2625 +/- 821 pg/mL, P =.013). Trends
      towards a decrease in levels of TNF-alpha and soluble receptor 1 were also seen
      in the bike group only. No change in circulating inflammatory markers was
      observed after stimulator training. CONCLUSIONS: Physical training improves
      exercise capacity for patients with chronic heart failure but degree of
      attenuation of the proinflammatory response may depend on the mode of training
      despite similar improvements in exercise capacity.

PMID- 14691427
TI  - Impact of lifestyle habits on the prevalence of the metabolic syndrome among
      Greek adults from the ATTICA study.
AB  - BACKGROUND: Individuals with the metabolic syndrome (MS) are at high risk for
      coronary heart disease and may benefit from aggressive lifestyle modification. In
      this study, we evaluated the effect of leisure time physical activity (PA) and
      the Mediterranean diet (MD) on the prevalence of the MS. METHODS: The ATTICA
      study is a health and nutritional survey. On the basis of a multistage, random
      sampling, 1128 men and 1154 women (>18 years old) without any evidence of
      cardiovascular disease or diabetes mellitus were enrolled from the greater Athens
      area during 2001 to 2002. The MS was defined according to the National
      Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria. PA
      was determined from a detailed questionnaire and graded according to the kcal/min
      expanded. MD was assessed through a validated nutrient questionnaire. RESULTS:
      The overall prevalence of the MS was 453 of 2282 subjects (19.8%). Of these
      subjects, 284 (25.2%) were men and 169 (14.6%) were women (P <.001). The
      prevalence of the MS increased accordingly to age (P for trend <.001). With
      multiple logistic regression analysis, the odds ratio of having the MS when the
      participant consumed the MD was 0.81 (95% CI, 0.68-0.976), and when even a little
      to moderate PA (<7 kcal/min)was reported, the odds ratio was 0.75 (95% CI, 0.65
      0.86). The higher levels of inflammation and coagulation markers among
      participants with MS did not explain much of the aforementioned effect of
      lifestyle modification. CONCLUSION: MS is common in Greece and is becoming even
      more common in the middle-aged population. The suggested therapeutic lifestyle
      approach may contribute to the reduction of the prevalence of the MS, beyond the
      levels of several lipid, inflammation, and coagulation markers.

PMID- 14691428
TI  - Exercise at ventilatory threshold aggravates left ventricular remodeling in
      patients with extensive anterior acute myocardial infarction.
AB  - BACKGROUND: The effects of physical training on ventricular remodeling after
      extensive anterior acute myocardial infarction (AMI) have not yet been defined.
      This randomized controlled study examines whether exercise aggravates left
      ventricular (LV) remodeling in patients with extensive anterior AMI. METHODS:
      Forty-eight consecutive patients with a first extensive anterior AMI and an LV
      ejection fraction (EF) of <45% assessed with left ventriculography (LVG) within 3
      days of onset were randomly allocated to a training group (n = 24) or a control
      group (n = 24). Exercise intensity was determined by the heart rate of each
      patient at ventilatory threshold (VT). Three weeks after onset, a second LVG was
      performed, followed by a supervised exercise program at VT for 12 weeks. The LVG
      was reassessed after the exercise program. We then calculated the global LV
      volume (end-diastolic volume index [EDVI], end-systolic volume index [ESVI]) and
      systolic expansion volume index (SEVI), a new parameter for measuring the
      infarction site expansion at the end-systolic phase. RESULTS: Both EDVI and ESVI
      significantly decreased in the control group from 1 to 4 months after onset (91.2
      +/- 26.1 to 83.3 +/- 24.0 mL/m2, P <.05; 52.4 +/- 22.5 to 45.7 +/- 18.8 mL/m2, P
      <.01, respectively), but not in the exercise group. The SEVI also significantly
      decreased in the control group from 1 to 4 months (33.1 +/- 16.9 to 25.7 +/- 13.9
      mL/m2, P <.05), but not in the training group (34.2 +/- 12.9 to 36.5 +/- 15.5
      mL/m2, P = not significant). CONCLUSION: Exercise while healing in patients with
      extensive anterior AMI, even at the VT level, induces LV enlargement and thus
      might aggravate LV remodeling. Therefore, in these patients, clinicians should
      consider withholding exercise training for at least 8 weeks, versus the 3-week
      period used in this trial.

PMID- 14691429
TI  - Cost of care distribution in atrial fibrillation patients: the COCAF study.
AB  - BACKGROUND: Atrial fibrillation (AF) currently represents a major economic burden
      for society. Very few studies have been performed to evaluate the cost of care
      for AF patients. This study is a large prospective survey designed to analyze the
      different cost drivers in the treatment of these patients. This survey, named
      Cost of Care in Atrial Fibrillation (COCAF), evaluated the cost of care for
      patients with AF treated by cardiologists in general office practice. METHODS: A
      group of 671 patients was recruited by 82 cardiologists distributed in all
      regions of France. The mean age of the patients was 69 years, and 64% were male.
      The mean follow-up was 329 +/- 120 days. The costs of care were analyzed from the
      health care payer and the societal perspectives. RESULTS: During the follow-up
      period, 21 patients (3.13%) died and 210 (31.3%) patients were hospitalized. The
      number of hospitalizations and deaths was significantly higher in the group of
      persistent or permanent AF (PEAF) patients, as compared to paroxysmal AF (PAAF)
      patients. Hospitalizations were much more frequent in the PEAF group (127) than
      in the PAAF group (83, P <.05). Deaths were also much more frequent in the PEAF
      group (17) as compared to the PAAF group (4, P <.001). From the societal
      perspective, the first cost driver was hospitalizations (52%), followed by drugs
      (23%), consultations (9%), further investigations (8%), loss of work (6%), and
      paramedical procedures (2%). In multivariate analysis the following parameters
      were significantly associated with higher costs: heart failure (P <.04), coronary
      artery disease (P <.001), use of class III antiarrhythmic drugs (P <.002),
      hypertension (P <.002) and metabolic disease (P <.001). CONCLUSIONS: This
      prospective survey shows that hospitalizations represent the major cost driver in
      the treatment of AF patients. Outpatient care programs must be proposed to AF
      patients in order to avoid readmissions and to reduce the cost of treatment.

PMID- 14691430
TI  - Automatic adjustment of pacing output in the clinical setting.
AB  - BACKGROUND: AutoCapture (AC) is a programmable feature that enables the pacemaker
      to both track the capture threshold and automatically adjust the output on a beat
      by-beat basis. Although AC safely and significantly reduces the current drainage,
      some authors have argued that the longevity benefit of such a system is
      overstated. This study aims to estimate the longevity extension that can be
      obtained, in the clinical routine, by turning the AC on in comparison to
      pacemakers programmed to operate at the shipped and manually optimized output.
      METHODS: We selected 83 consecutive patients who received implanted St Jude's
      Affinity pacemakers >6 months earlier. Eight patients died or were lost to follow
      up and in 9 subjects the AC could not be turned on. In the remaining 66 patients,
      current drain and estimated longevity were compared in 3 situations: (1) AC on;
      (2) AC off, optimized programming (100%-150% voltage threshold); (3) AC off,
      shipped output (3.5 V). RESULTS: Five patients had large variations (>1 V) of the
      AC threshold. Current drainage was 8.0 +/- 0.9 mA in the AC group, 8.7 +/- 1.8 mA
      with AC off and optimized programming, and 11.3 +/- 2.3 mA at shipped output (P
      <.01). Estimated longevity was significantly extended (P <.01) by AC (12.1 +/-
      1.0 years) when compared to shipped (8.9 +/- 1.7 years) and optimized programming
      (11.3 +/- 1.4 years). CONCLUSION: Reprogramming the pacemaker output
      significantly enhanced its estimated longevity; AC added a moderate but
      significant extension over manual reprogramming and was associated with increased
      safety in patients with large ventricular threshold variations.

PMID- 14691431
TI  - Benefits of direct angioplasty for women and men with acute myocardial
      infarction: results of the Global Use of Strategies to Open Occluded Arteries in
      Acute Coronary Syndromes Angioplasty (GUSTO II-B) Angioplasty Substudy.
AB  - BACKGROUND: Direct angioplasty (PTCA) and thrombolytic therapy are the chief
      therapies for treating an ST-segment elevation myocardial infarction (MI).
      OBJECTIVE: This study was designed to evaluate sex differences in the relative
      benefit of direct PTCA versus thrombolytic therapy among patients enrolled in the
      Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes
      Angioplasty (GUSTO II-B PTCA) Substudy. METHODS: Women and men presenting with an
      acute ST-segment elevation MI were randomized to receive either direct PTCA or
      accelerated tissue plasminogen activator (t-PA). Patients were then randomized to
      treatment with either heparin or bivalirudin. A gender analysis of outcome was
      performed. RESULTS: Women were older than men (68.6 +/- 11.5 vs 59.5 +/- 12.0
      years, P <.001) and were more likely to have diabetes (22.5% vs 13.5%, P <.0001)
      and hypertension (53.3% vs 34.8%, P =.001). After adjusting for differences in
      baseline variables, the odds ratio (OR) for reaching a 30-day clinical end point
      (death, nonfatal infarction, or nonfatal disabling stroke) was similar for women
      and men (1.35, 95% CI 0.88-2.08). The OR for reaching a clinical end point at 30
      days for the PTCA-treated women compared with the t-PA-treated women was 0.685
      (95% CI 0.36-1.32) and similar to the OR in men, 0.565 (95% CI 0.35-0.91), P for
      interaction =.535. Because women had a higher event rate than men, the absolute
      number of major events prevented when treating women with direct PTCA was higher
      than men (56 events/1000 women treated with PTCA vs 42 events per 1000 men
      treated with PTCA). CONCLUSIONS: Although the relative benefit of direct PTCA to
      t-PA for the treatment of an acute MI appears to be similar in women and men,
      women may derive a larger absolute benefit from direct PTCA.

PMID- 14691432
TI  - Incidence, correlates, management, and clinical outcome of coronary perforation:
      analysis of 16,298 procedures.
AB  - BACKGROUND: Coronary perforation is a serious but uncommon complication of
      percutaneous coronary intervention (PCI) and is associated with significant
      morbidity and mortality. METHODS: We performed an analysis of the Mayo Clinic PCI
      database. Clinical records, procedural reports, and angiographic studies were
      reviewed. Multiple logistic regression analysis was performed to identify
      clinical, procedural, anatomic, and angiographic correlates of coronary
      perforation. RESULTS: A total of 16,298 PCI procedures were performed between
      January 1990 and December 2001. We identified 95 coronary perforations (0.58%;
      95% CI, 0.47-0.71). The incidence of coronary perforation varied with time.
      Correlates of coronary perforation included the use of an atheroablative device
      and female sex. Twelve patients (12.6%) sustained an acute myocardial infarction,
      and cardiac tamponade developed in 11 patients (11.6%). Management strategies
      included reversal of heparin, pericardiocentesis, placement of a covered stent,
      and surgical repair. Seven patients died (7.4%). CONCLUSIONS: Coronary
      perforation during PCI is rare, but is associated with significant morbidity and
      mortality. The variable frequency of perforation may be explained by temporal
      variations in the use of atheroablative devices.

PMID- 14691433
TI  - Predictors of repeat revascularization after nonemergent, first percutaneous
      coronary intervention in the community.
AB  - BACKGROUND: We sought to determine the incidence of and risk factors for repeat
      revascularization after nonemergent, first percutaneous coronary intervention
      (PCI) performed in contemporary community practice. METHODS: We analyzed a
      prospective registry of consecutive patients undergoing isolated PCI in the state
      of Washington. Multivariate Cox regression analysis was used to determine
      predictors of repeat revascularization (by PCI or bypass surgery) within 1 year
      after first PCI. RESULTS: Between January 1, 1999, and December 31, 1999, there
      were 3571 nonemergent first PCIs, 87.7% of which involved stent placement. Repeat
      revascularization occurred in 577 (16.2%) patients. Repeat revascularization was
      predicted by multivessel disease (hazard ratio [HR] 1.36, 95% CI 1.12-1.66),
      stable versus no angina (HR 1.27, 95% CI 1.03-1.57), and maximum stent length
      used (per 1 mm longer: HR 1.01, 95% CI 1.002-1.02), while prior myocardial
      infarction (HR 0.77, 95% CI 0.62-0.96) and creatinine >1.2 mg/dL (HR 0.74, 95% CI
      0.56-0.98) were associated with lower risk of repeat revascularization. Diabetes
      was a significant predictor only when the outcome was limited to
      revascularization by coronary artery bypass surgery (HR 1.52, 95% CI 1.03-2.23).
      Although glycoprotein IIb/IIIa inhibitor use was a significant univariate
      predictor of freedom from early repeat revascularization (within 60 days after
      first PCI), after controlling for potential confounders, it was no longer
      significant. CONCLUSIONS: In this contemporary, community-based registry of
      patients undergoing nonemergent first PCI, clinical practice and outcomes are
      consistent with evidence from clinical trials and previous controlled studies.
      Results from controlled studies may reasonably be extrapolated to such a
      community setting.

PMID- 14691434
TI  - Importance of echocardiography in patients with severe nonischemic heart failure:
      the second Prospective Randomized Amlodipine Survival Evaluation (PRAISE-2)
      echocardiographic study.
AB  - BACKGROUND: Echocardiography is used commonly in clinical practice when caring
      for patients with heart failure. It is unknown whether the presence of certain
      findings provides an incremental ability to predict survival beyond the use of
      baseline clinical findings alone. The second PRAISE-2 echocardiographic study was
      prospectively designed to identify echocardiographic predictors of survival among
      patients with nonischemic cardiomyopathy and heart failure and to determine if
      components of the echocardiographic examination add prognostic information to
      baseline demographic and clinical information. METHODS: One hundred patients
      participated in the second Prospective Randomized Amlodipine Survival Evaluation
      Study (PRAISE-2) echocardiographic study; of these, 93 had full and interpretable
      echocardiographic examinations. Cox proportional hazards modeling was used to
      assess the relation between various characteristics and survival as well as to
      assess the incremental prognostic information gained by echocardiography beyond
      the clinical examination. RESULTS: Seven of 10 routine echocardiographic measures
      were significantly associated with death. These included mitral regurgitation
      (hazard ratio [HR], 2.31; 95% CI, 1.02, 5.27), left ventricular ejection fraction
      <20% (HR, 2.59; 95% CI, 1.14, 5.88), restrictive left ventricular filling pattern
      (HR, 2.37; 95% CI, 1.05, 5.32), and peak D velocity (HR, 1.62; 95% CI, 0.38,
      0.87). The only statistically significant clinical predictor of survival was
      dyspnea at rest. The addition any of several echocardiographic parameters to
      baseline clinical information significantly improved the ability to predict
      survival. CONCLUSIONS: Several readily available echocardiographic parameters are
      predictive of death and when added to clinical examination findings significantly
      improve the ability to determine prognosis among patients with nonischemic
      cardiomyopathy and heart failure.

PMID- 14691435
TI  - Association between plasmin activation system and intravascular ultrasound signs
      of plaque instability in patients with unstable angina and non-st-segment
      elevation myocardial infarction.
AB  - BACKGROUND: The association between intravascular ultrasound (IVUS) signs of
      plaque instability and plasma levels of biomarkers was determined in patients
      with unstable angina and non-ST-segment elevation myocardial infarction
      (UA/NSTEMI). METHODS: Fifty-two patients underwent coronary angiography and IVUS
      8 +/- 5 hours after the onset of chest pain. IVUS analysis included plaque
      morphology, disruption, thrombi and eccentricity, lumen, external elastic
      membrane, and plaque plus media areas of culprit lesion and reference segments
      and arterial remodeling. Plasma levels of the thrombin activation system
      (thrombin-antithrombin complex [TAT], tissue factor pathway inhibitor [TFPI], and
      prothrombin fragments 1+2 [F1+2]) and plasmin activation system (tissue and
      urokinase-type plasminogen activator [t-PA and u-PA], plasminogen activator
      inhibitor-1 [PAI-1], and D-dimer) were measured with enzyme-linked immunosorbent
      assay kits before angiography. RESULTS: Elevated levels of TAT (7.2 +/- 6.0
      microg/L), F1+2 (1.8 +/- 1.0 nmol/L), TFPI (179.1 +/- 131.0 ng/mL), PAI-1 (95.4
      +/- 54.6 ng/mL), t-PA (10.6 +/- 8.8 ng/mL), and u-PA (2.6 +/- 0.9 ng/mL) were
      found in patients with UA/NSTEMI. The serum levels of D-dimer (40.0 +/- 39.5
      ng/mL) remained in reference range. Expansive and constrictive remodeling were
      found in 18 (35%) and 12 (23%) patients, respectively. Expansive remodeling of
      the culprit lesion was associated with significantly higher plasma levels of PAI
      1 (121.6 +/- 55.0 vs 87.7 +/- 61.5 and 77.4 +/- 42.8 ng/ml, P =.039), and u-PA
      (3.0 +/- 1.2 vs 2.2 +/- 0.5 and 2.5 +/- 0.7 ng/mL, P =.026) as compared with
      constrictive and neutral remodeling. Increased plasma levels of u-PA were
      associated with plaque rupture (3.0 +/- 0.7 vs 2.5 +/- 0.9 ng/mL, P =.062).
      Plasma levels of PAI-1 and u-PA correlated positively with plaque plus media (P
      =.0297 and P =.0093) and external elastic membrane areas (P =.010 and P =.0002).
      CONCLUSIONS: Elevated levels of biomarkers of plasmin activation system are
      associated with signs of plaque instability of culprit lesion in UA/NSTEMI and
      might therefore serve as non-invasive determinants of the population that is at
      high risk for subsequent adverse events.

PMID- 14691436
TI  - Doppler-echocardiographic assessment of pulmonary regurgitation in adults with
      repaired tetralogy of Fallot: comparison with cardiovascular magnetic resonance
      imaging.
AB  - AIMS: The purpose of this study was to compare the noninvasive assessment of
      severity of pulmonary regurgitation with Doppler echocardiography versus
      cardiovascular magnetic resonance imaging (CMR) in adult patients with repaired
      tetralogy of Fallot (rTOF). METHODS: We studied 52 (22 females) consecutive
      patients (aged 32 +/- 2 years, 23 +/- 5 years after rTOF) using Doppler
      echocardiography and compared these findings with CMR. From the continuous-wave
      Doppler trace, the duration of pulmonary regurgitation and of total diastole was
      measured and the ratio between the 2 was defined as pulmonary regurgitation index
      (PRi). Pulmonary regurgitant fraction (PRF) was assessed with flow phase velocity
      mapping with CMR. RESULTS: Patients were divided into 2 groups according to the
      median value (24.5%) of PRF measured by CMR: Group I (26 patients) with PRF < or
      =24.5% and Group II with PRF >24.5%. There was no difference between patients'
      age, sex, or age at repair between the 2 groups. More patients from Group II had
      a right ventricular outflow or transannular patch repair compared to Group I
      (12/26 [46%] vs 6/26 [23%], P <.01). Mean pulmonary regurgitation time was
      shorter (340 +/- 60 vs 440 +/- 135 ms, P =.001) and PRi was lower (0.61 +/- 0.11
      vs 0.91 +/- 0.11, P <.001) in Group II compared to Group I. Color Doppler
      regurgitant jet was also broader in Group II (1.4 +/- 0.4 vs 0.7 +/- 0.5 cm, P
      <.001), signifying more severe pulmonary regurgitation. Doppler-measured PRi
      correlated closely with CMR regurgitant fraction (r = -0.82, P <.001) and with
      color Doppler pulmonary regurgitant jet width (r = -0.66, P <.001); the latter
      correlated with PRF assessed with CMR (r = 0.72, P <.001). A PRi <0.77 had 100%
      sensitivity and 84.6% specificity for identifying patients with pulmonary
      regurgitant fraction >24.5%, with a predictive accuracy of 95%. Furthermore,
      echocardiographically-assessed right ventricular end-diastolic dimensions
      correlated with CMR end-diastolic volume index (r = 0.49, P <.001 ). CONCLUSIONS:
      Pulmonary regurgitation is common in asymptomatic adults with rTOF. Severity of
      pulmonary regurgitation and its effects on right ventricular dimensions in these
      patients can be assessed noninvasively by Doppler echocardiography and CMR, with
      reasonable agreement between the 2 techniques.

PMID- 14691437
TI  - Pharmacokinetics and safety of TP10, soluble complement receptor 1, in infants
      undergoing cardiopulmonary bypass.
AB  - BACKGROUND: Increase in vascular permeability and multiorgan dysfunction after
      cardiopulmonary bypass (CPB) are barriers to successful cardiac surgery in
      infants. Complement inhibition with TP10, a C3/C5 convertase inhibitor (AVANT
      Immunotherapeutics, Needham, Mass), blunts post-CPB organ dysfunction in the
      neonatal pig. Methods and results The pharmacokinetics and safety of TP10 in
      infants (age <1 year, n = 15) undergoing CPB were examined in a phase I/II open
      label prospective trial. TP10 (10 mg/kg) was given intravenously before CPB and
      also added (10 mg/100 mL prime volume) to the CPB circuit. TP10 plasma levels
      correlated with C3a levels and measures of clinical course. All infants survived.
      No adverse events were attributed to TP10. TP10 plasma concentration fell to < or
      =60 microg/mL 12 hours after CPB. A 2-compartment model was fit to the TP10 blood
      levels as a function of time. Based on this model, an initial dose of 10 mg/kg
      over 0.5 hours followed by 10 mg/kg over 23.5 hours is the most appropriate for
      maintaining TP10 concentration between 100 microg/mL and 160 microg/mL for 24
      hours after CPB. C3a was lower 12 hours after CPB than before CPB and still lower
      24 hours after CPB. TP10 concentration was inversely correlated with the 12-hour
      post-CPB to pre-CPB ratio of C3a (Spearman rho -0.76, P = -.016), and with total
      (rho -0.56, P =.047) and net (rho -0.85, P =.0016) fluid and blood product
      administration/kg >24 hours after CPB. CONCLUSIONS: TP10 administration to
      infants appears safe. Pharmacokinetic analysis generated an optimal dosing
      strategy to achieve effective TP10 levels for 24 hours after CPB. In the infant,
      TP10 appears to decrease CPB-induced complement activation and protect vascular
      function. These results support a phase III trial of TP10 in infants requiring
      CPB.

PMID- 14691438
TI  - Interaction between a genetic variant of the platelet fibrinogen receptor and
      fibrinogen levels in determining the risk of cardiovascular events.
AB  - BACKGROUND: The PlA1A2 polymorphism of glycoprotein IIIa (GPIIIa), which affects
      postoccupancy signaling by the platelet fibrinogen receptor IIbIIIa, has been
      investigated as a potential genetic risk factor for cardiovascular events in
      numerous studies, without consistent results. We investigated whether the effect
      of this genetic variant of the platelet fibrinogen receptor on the risk of
      cardiovascular events is affected by fibrinogen plasma levels. METHODS: The
      GPIIIa PlA1A2 polymorphism and fibrinogen levels were determined in 455 men with
      angiographically documented coronary atherosclerosis. RESULTS: Neither
      carriership of the rare PlA2 allele nor fibrinogen plasma levels affected the
      time to cardiovascular event, as assessed in a proportional hazards model.
      However, there was a significant interaction between PlA2 carriership and
      fibrinogen plasma levels (P =.002). Carriership of the variant PlA2 allele
      significantly affected event-free survival only in individuals within the highest
      fibrinogen quartile (hazard ratio, 2.7; 95% CI, 1.1 to 7.1; P =.03). CONCLUSIONS:
      We observed a statistically significant interaction between a genetic variant of
      the platelet fibrinogen receptor and fibrinogen levels in determining the risk of
      cardiovascular events. This interaction may account for the inconsistent results
      of genetic association studies investigating this genotype as a genetic risk
      factor in thrombotic cardiovascular events.

PMID- 14691439
TI  - Effect of tirofiban on C-reactive protein in non-ST-elevation myocardial
      infarction.
AB  - OBJECTIVES: C-reactive protein (CRP) is a prototypic marker of inflammation. The
      effect of tirofiban on CRP levels in patients with non-ST-elevation myocardial
      infarction (NSTEMI) was investigated. METHODS: The present study was prospective
      and randomized. Patients with NSTEMI received aspirin, clopidogrel, statin, and
      unfractionated heparin. Patients with NSTEMI were enrolled into either the
      tirofiban + heparin group (group 1: n = 25) or the heparin group (group 2: n =
      32). Levels of CRP were determined at baseline and after 48 and 72 hours. Heparin
      and tirofiban were discontinued after 48 hours. RESULTS: Levels CRP of were
      similar in two groups at baseline; they increased significantly at 48 hours and
      72 hours in the control group but not in the tirofiban group. The differences on
      and after treatment were statistically significant. In group 1, CRP elevation was
      attenuated after tirofiban infusion compared with group 2. CONCLUSIONS: Products
      of platelet activation may aid neutrophil accumulation and enhance inflammation.
      Activated leukocytes and platelets potentate each others' effects. Tirofiban
      strongly inhibits the platelet aggregation. The decreased platelet aggregation
      can suppress the inflammatory protein, chemokine, and adhesion molecule
      expression. After the tirofiban infusion, CRP elevation was atteunated in
      patients with NSTEMI.

PMID- 14691440
TI  - Effects of carvedilol therapy on restrictive diastolic filling pattern in chronic
      heart failure.
AB  - BACKGROUND: Carvedilol therapy during congestive heart failure demonstrated a
      good efficacy in mortality rate reduction and in improvement of left ventricular
      (LV) systolic performance. However, currently there is not any finding about the
      drug's effect on diastolic filling. The aim of this study was to evaluate the
      effects of beta-blocker treatment on LV diastolic function with an eco-pulsed
      Doppler ultrasound scanning examination at transmitral level in a group of
      patients who were affected by heart failure with a restrictive filling pattern.
      METHODS: We studied 27 patients with idiopathic or ischemic dilated
      cardiomyopathy with LV severe systolic disfunction (ejection fraction <35%).
      Fourteen patients were randomized to receive carvedilol treatment (carvedilol
      group), and 13 patients continued to receive standard therapy with angiotensin
      converting enzyme inhibitors, diuretics, and vasodilators (placebo group). All
      patients underwent an echo-Doppler ultrasound scanning examination at the
      beginning of the study and after 4 and 12 months of treatment. RESULTS: In the
      carvedilol group, we found a progressive improvement of Doppler ultrasound
      scanning parameters after 4 months, with a significant increase of A wave (P
      <.005), deceleration time (DT; P <.02) and isovolumetric relaxation time (IVRT; P
      <.02). These improvements were confirmed after 1 year of follow-up, whereas
      patients in the placebo group did not shown any significant modifications. After
      1 year, the differences in these groups were more significant for A wave (39 +/-
      4 cm/sec carvedilol group vs 30 +/- 4 cm/sec placebo group; P <.0001), for E/A
      ratio (1.8 +/- 0.2 carvedilol group vs 2.6 +/- 0.5 placebo group; P <.0002), for
      DT 1(40 +/- 16 msec carvedilol group vs 112 +/- 13 msec placebo group; P <.001),
      and for IVRT (74 +/- 8 msec carvedilol group vs 57 +/- 7 mesc placebo group; P
      <.0002). These changes seem to happen before systolic and morphological
      modifications. CONCLUSION: Our results show that carvedilol therapy is a means of
      modifying parameters of diastolic filling favorably in patients with heart
      failure. These effects seem to be independent of those of systolic function. The
      improvement of systolic performance occurs after 1 year of treatment. The
      restrictive filling pattern, related to an unfavorable prognosis, changes toward
      pseudonormal or altered relaxation pattern during carvedilol therapy. Further
      investigations with a greater sample size will be necessary to confirm our
      findings.

PMID- 14691441
TI  - Rapid loading of sotalol or amiodarone for management of recent onset symptomatic
      atrial fibrillation: a randomized, digoxin-controlled trial.
AB  - BACKGROUND: Amiodarone and sotalol are commonly used for the maintenance of sinus
      rhythm, but the efficacy of these agents administered as high-dose infusions for
      rapid conversion of atrial fibrillation is unknown. Use in this context would
      facilitate drug initiation in patients in whom ongoing prophylactic therapy is
      indicated. METHODS: We assessed the efficacy and safety of rapid high-dose
      intravenous infusions of amiodarone and sotalol for heart rate control and rapid
      reversion to sinus rhythm in patients who came to the emergency department with
      recent-onset symptomatic atrial fibrillation. Patients (n = 140) were randomized
      to receive 1.5mg/kg of sotalol infused in 10 minutes, 10mg/kg of amiodarone in 30
      minutes, or 500 microg of digoxin in 20 minutes. Electrical cardioversion was
      attempted for patients not converting to sinus rhythm within 12 hours. RESULTS:
      The rapid infusion of sotalol or amiodarone resulted in more rapid rate control
      than digoxin. Each of the 3 trial strategies resulted in similar rates of
      pharmacological conversion to sinus rhythm (amiodarone, 51%; sotalol, 44%;
      digoxin, 50%; P = not significant). The overall rates of cardioversion after
      trial drug infusion and defibrillation were high for all groups (amiodarone, 94%;
      sotalol, 95%,; digoxin, 98%; P = not significant), but there was a trend toward a
      higher incidence of serious adverse reactions in the amiodarone group.
      CONCLUSION: The rapid infusion of sotalol or amiodarone in patients with
      symptomatic recent-onset atrial fibrillation results in rapid control of
      ventricular rate. Even with high-dose rapid infusions, all 3 agents are
      associated with a poor overall reversion rate within 12 hours. Almost all
      patients were returned to sinus rhythm with a combination of pharmacological
      therapy and electrical cardioversion.

PMID- 14691442
TI  - Promising efficacy of primary gradual and prolonged balloon angioplasty in small
      coronary arteries: a randomized comparison with cutting balloon angioplasty and
      conventional balloon angioplasty.
AB  - BACKGROUND: Small vessel size represents a critical risk factor for an adverse
      outcome after both conventional balloon angioplasty (POBA) and stenting. Gradual
      and prolonged balloon angioplasty (GPBA) has been shown to cause less arterial
      trauma, which results in higher procedural success rates and fewer in-hospital
      complications than POBA. The aim of this study was to assess the clinical and
      angiographic benefits of primary GPBA with a perfusion balloon in small coronary
      arteries, as compared with cutting balloon angioplasty (CBA) and POBA. METHODS: A
      total of 263 patients with symptoms and reference diameters <3.0 mm were randomly
      assigned to undergo GPBA (n = 85), CBA (n = 88), or POBA (n = 90). The cumulative
      inflation time must be >10 minutes in GPBA. Crossover to stent was allowed for
      inadequate results. Follow-up angiography was performed after 6 months. The
      primary end point was angiographic restenosis at follow-up. RESULTS: Compared
      with POBA, GPBA resulted in a lower final residual diameter stenosis (27.3% vs
      34.2%, P =.01) and decreased the need for stent placement (8.0% vs 22.2%, P
      =.031). At follow-up, the restenosis rates were lower with GPBA (31.3%, P =.034)
      and CBA (32.9%, P =.059) than POBA (50.6%). Target lesion revascularization was
      less frequently needed with GPBA (20.5%, P =.043) and CBA (20.0%, P =.033) than
      POBA (37.6%). Additionally, the event-free survival rate was higher with GPBA
      (77.1%, P =.033) and CBA (76.4%, P =.047) than POBA (58.8%). CONCLUSIONS: In
      small coronary arteries, both GPBA and CBA resulted in favorable angiographic and
      clinical outcomes. With a lower restenosis rate and target lesion
      revascularization rate, GPBA may be a superior strategy for small vessels
      compared with POBA.

PMID- 14691443
TI  - Targeted ultrasonic contrast agents for molecular imaging and therapy.
AB  - Targeted contrast agents are expanding the detectability and diagnosis of
      pathology from a strict anatomic to biochemical basis. Moreover, these new
      agents, in their various forms, offer the potential for site-specific drug and
      gene delivery, i.e., the "magic bullet" first postulated by Paul Erhlich 100
      years ago. The ability to direct drugs to the molecular signatures of disease, to
      confirm noninvasively their presence at the site-of-interest, and to quantify the
      adequacy of local drug concentration at the time of treatment, ie, rational
      targeted drug delivery, offers exciting new clinical paradigms in the near
      future.

PMID- 14691444
TI  - Bone morphogenetic protein-5, -6 and -7 inhibit growth and induce apoptosis in
      human myeloma cells.
AB  - Previously, bone morphogenetic protein (BMP)-2 and -4 have been shown to inhibit
      proliferation and induce apoptosis in human myeloma cells. BMP-2 and -4 belong to
      a subgroup of BMPs using the BMP receptors Alk-3 or -6. In this study, we
      examined the effects on human myeloma cells of BMP-6 and -7, members of a
      different BMP subgroup, which mainly utilize Alk-2 as their receptor. All cell
      lines examined expressed mRNA for the BMP-6 and -7 receptor Alk-2. We did not
      detect transcripts for the BMP-2 and -4 receptors Alk-3 or Alk-6 in INA-6 and
      RPMI-8226 cells by RT-PCR. Accordingly, the intracellular signalling molecules
      Smad-1, -5 and -8 were not phosphorylated by BMP-4 in INA-6 and RPMI-8226 cells.
      The expression patterns of various BMP receptors in the myeloma cell lines
      explained the differences in responses to the various BMPs. Alk-2-expressing cell
      lines responded with growth inhibition and apoptosis to BMP-6 and -7, whereas
      cell lines lacking both Alk-3 and -6 were resistant to BMP-4. Soluble Alk-3 and 
      6 were able to neutralize the BMP-4 effects in BMP-4-responsive cell lines. All
      BMPs reduced viability in more than 70% of purified primary myeloma cell samples.
      BMPs have intriguing antitumor effects in vitro. Importantly, myeloma cells not
      responsive to BMP-2 and -4 may still be sensitive to BMP-6 or -7. It is possible
      that therapeutic use of BMP or BMP analogues could have an impact on both myeloma
      bone disease and myeloma cell growth.

PMID- 14691445
TI  - Role of the C-terminal alpha-helical domain of the von Hippel-Lindau protein in
      its E3 ubiquitin ligase activity.
AB  - In the present study, the role of the C-terminal alpha-helical domain (amino acid
      (aa) 195-208) of the von Hippel-Lindau (VHL) tumour suppressor was investigated.
      Deletions of the VHL C-terminus up to the naturally occurring 195-Gln-Term
      resulted in hypoxia-inducible factor (HIF)-1alpha downregulation in renal cell
      carcinoma (RCC)4 cells during normoxia, suggesting that this domain is not an
      absolute requirement for the ubiquitination of HIF-1alpha. However, detailed
      investigation of the ubiquitin protein isopeptide ligase ubiquitin ligase
      properties of VHL revealed C-terminal deletions to cause a significant impairment
      of HIF-1alpha ubiquitination, which is shown to be due to a loss in high-affinity
      binding to the target substrate. When VHL regulation of both HIF-1alpha N- and C
      terminal oxygen-dependent degradation domains (HIF-ODDD) was investigated, it was
      found that only ubiquitination of the C-terminal HIF-ODDD was affected by the
      deletion of the VHL C-terminus. When RCC4 cells expressing C-terminal truncations
      of VHL were exposed to graded hypoxia, differences in the induction of HIF-1alpha
      were observed in comparison with full-length VHL, with a shift in the maximal
      induction of HIF-1alpha to a higher oxygen tension. These changes were
      accompanied by increased glucose transporter 1 expression, p300 CH1 domain
      binding and HIF-mediated reporter activity. We have thus defined a role for the C
      terminal alpha-helical domain of VHL in the regulation of HIF-1alpha.

PMID- 14691446
TI  - Variation in cadherins and catenins expression is linked to both proliferation
      and transformation of Rhabdomyosarcoma.
AB  - Cadherins are a family of transmembrane glycoproteins that mediate Ca(2+)
      dependent homophilic cell-cell adhesion and play a crucial role in cell
      differentiation. E-cadherin-mediated cell-cell adhesion is lost during the
      development of most epithelial cancers. This study examines cadherin-dependent
      adhesion in cell lines derived from rhabdomyosarcoma (RMS), a highly malignant
      soft-tissue tumor committed to the myogenic lineage, but arrested prior to
      terminal differentiation. We analysed the expression of cadherins and associated
      catenins at the mRNA and protein levels as well as their localization in nine RMS
      derived cell lines relative to normal myoblasts. We show a decrease in the
      expression of cadherins and catenins in all RMS-derived cell lines compared to
      control cells. This decrease in the expression of N- and M-cadherin was confirmed
      in RMS biopsies. In contrast, R-cadherin is found expressed in RMS, whereas it is
      normally absent in normal myoblasts. We show that a decrease of R-cadherin
      expression using RNA interference inhibits cell proliferation of the RD cell
      line. In addition to their diminished expression, cadherins and catenins do not
      localize to intercellular contacts in embryonal RMS (ERMS), whereas specific
      persistent localization is seen in alveolar RMS (ARMS)-derived cell lines. Thus,
      RMS exhibit defects in the expression of molecules of the cadherin family.
      Defects in the localization of these adhesion molecules at the sites of cell-cell
      contact are specifically observed in the ERMS subtype. In addition, our data
      suggest that R-cadherin is a specific diagnostic marker for RMS and is also an
      important factor of RMS cell proliferation.

PMID- 14691447
TI  - Microarray analysis identifies Autotaxin, a tumour cell motility and angiogenic
      factor with lysophospholipase D activity, as a specific target of cell
      transformation by v-Jun.
AB  - We have used chicken cDNA microarrays to investigate gene-expression changes
      induced during transformation of chick embryo fibroblasts (CEF) by the viral Jun
      oncoprotein encoded by ASV17. This analysis reveals that v-Jun induces increases
      and decreases of varying magnitude in the expression of genes involved in diverse
      cellular functions, most of which have not been detected in previous screens for
      putative v-Jun targets. In all, 27 individual genes were identified, whose
      expression is increased threefold or more in v-Jun-transformed cells, including
      genes involved in energy generation, protein synthesis, and gene transcription.
      Interestingly, this group includes the hypoxia-inducible factor-1 alpha (Hif
      1alpha) transcription factor and the glycolytic enzyme enolase, suggesting that
      adaptation to hypoxia could play a role in tumorigenesis by v-Jun. We also
      identified 32 genes whose expression is decreased threefold or more, including
      chaperones, components of the cytoskeleton, and, unexpectedly, DNA replication
      factors. The gene whose expression is upregulated most dramatically
      (approximately 100-fold) encodes Autotaxin (ATX), a secreted tumor motility
      promoting factor with lysophospholipase D activity. Strikingly, v-Jun-transformed
      CEF secrete catalytically active ATX and chemotactic activity, which can be
      detected in conditioned medium. ATX is not detectably expressed in normal CEF or
      CEF transformed by the v-Src or v-Myc oncoproteins, indicating that induction of
      this putative autocrine/paracrine factor is a specific consequence of cell
      transformation by v-Jun. ATX has been implicated in both angiogenesis and
      invasion, and could therefore play an important role in tumorigenesis by v-Jun in
      vivo.

PMID- 14691448
TI  - Transgenic mouse model for breast cancer: induction of breast cancer in novel
      oncogene HCCR-2 transgenic mice.
AB  - Transgenic mice containing novel oncogene HCCR-2 were generated to analyse the
      phenotype and to characterize the role of HCCR-2 in cellular events. Mice
      transgenic for HCCR-2 developed breast cancers and metastasis. The level of p53
      in HCCR-2 transgenic mice was elevated in most tissues including breast, brain,
      heart, lung, liver, stomach, kidney, spleen, and lymph node. We examined whether
      stabilized p53 is functional in HCCR-2 transgenic mice. Defective induction of
      p53 responsive genes including p21WAF1, MDM2, and bax indicates that stabilized
      p53 in HCCR-2 transgenic mice exists in an inactive form. These results suggest
      that HCCR-2 represents an oncoprotein that is related to breast cancer
      development and regulation of the p53 tumor suppressor.

PMID- 14691449
TI  - An agonist to the A3 adenosine receptor inhibits colon carcinoma growth in mice
      via modulation of GSK-3 beta and NF-kappa B.
AB  - A(3) adenosine receptor (A(3)AR) activation with the specific agonist CF101 has
      been shown to inhibit the development of colon carcinoma growth in syngeneic and
      xenograft murine models. In the present study, we looked into the effect of CF101
      on the molecular mechanisms involved in the inhibition of HCT-116 colon carcinoma
      in mice. In tumor lesions derived from CF101-treated mice, a decrease in the
      expression level of protein kinase A (PKA) and an increase in glycogen synthase
      kinase-3 beta (GSK-3 beta) was observed. This gave rise to downregulation of beta
      catenin and its transcriptional gene products cyclin D1 and c-Myc. Further
      mechanistic studies in vitro revealed that these responses were counteracted by
      the selective A(3)AR antagonist MRS 1523 and by the GSK-3 beta inhibitors lithium
      and SB216763, confirming that the observed effects were A(3)AR and GSK-3 beta
      mediated. CF101 downregulated PKB/Akt expression level, resulting in a decrease
      in the level and DNA-binding capacity of NF-kappa B, both in vivo and in vitro.
      Furthermore, the PKA and PKB/Akt inhibitors H89 and Worthmannin mimicked the
      effect of CF101, supporting their involvement in mediating the response to the
      agonist. This is the first demonstration that A(3)AR activation induces colon
      carcinoma growth inhibition via the modulation of the key proteins GSK-3 beta and
      NF-kappa B.

PMID- 14691450
TI  - MASL1, a candidate oncogene found in amplification at 8p23.1, is translocated in
      immunoblastic B-cell lymphoma cell line OCI-LY8.
AB  - Genetic amplification at chromosome 8p23.1 has been reported in some solid
      tumors. Translocation of 8p23.1 has also been reported in hematological
      malignancies and head and neck squamous cell cancer. In an attempt to clarify
      whether this translocation is implicated in lymphomagenesis, we performed FISH
      analysis of the immunoblastic B-cell lymphoma cell line OCI-LY8, which has
      chromosome translocation at 8p23.1, with various BAC clones. We found split
      signals on BAC, RP11-18L2 where the MASL1 gene is located. This translocation was
      found to produce a chimeric transcript of MASL1 exon 1 with a cryptic exon from
      the genome region at 14q21. Our study indicates that MASL1 is not only a target
      gene for genomic amplification but also for chromosomal translocation. Since
      tumorigenic activity of the MASL1 has not been proven, its in vitro transforming
      activity was studied and in vivo nude mice assay were performed. Although no in
      vitro transforming activity was detected by focus formation, the in vivo
      tumorigenesis assay with nude mice showed that both MASL1 and chimeric MASL1
      possess tumorigenic activity. This suggests that MASL1 is an important oncogene
      not only for solid tumors but also for hematologic malignancies.

PMID- 14691451
TI  - Proteasome inhibitor MG132 upregulates death receptor 5 and cooperates with
      Apo2L/TRAIL to induce apoptosis in Bax-proficient and -deficient cells.
AB  - Apo2L/TRAIL (tumor necrosis factor-related apoptosis inducing ligand (TRAIL),
      also known as Apo2L) is a potentially important anticancer agent awaiting
      clinical trials. Unfortunately, however, some cancer cells exhibit resistance to
      Apo2L/TRAIL, which could limit the use of this potentially promising anticancer
      agent. Although the molecular basis of the inherent or acquired resistance to
      Apo2L/TRAIL remains unclear, previous studies indicate that Bax deficiency can
      confer resistance to Apo2L/TRAIL. Proteasome inhibition is also emerging as a
      promising therapeutic strategy to manage human malignancies. Here, we report that
      proteasome inhibitor MG132 upregulates Apo2L/TRAIL death receptor 5 expression in
      both Bax-proficient and -deficient HCT116 cells. MG132 effectively cooperated
      with Apo2L/TRAIL to induce apoptosis in both Bax-proficient and -deficient cells
      that was coupled with caspases-8 and -3 activation and Bid cleavage. Although
      both agents in combination also induced cytochrome c and Smac release from
      mitochondria into cytosol and activated caspase-9 in Bax-proficient cells, their
      effects on these events were significantly diminished in Bax-deficient cells.
      These results suggest that Bax is not absolutely required for death receptor 5
      dependent apoptotic signals and MG132 by upregulating DR5 effectively cooperates
      with Apo2L/TRAIL to overcome Bax deficiency-induced resistance to Apo2L/TRAIL.
      Our results have important clinical implications in that the use of Apo2L/TRAIL
      and proteasome inhibitors in combination could prove to be a novel therapeutic
      strategy to manage the Apo2L/TRAIL-resistant tumors.

PMID- 14691452
TI  - Abnormal production of the TNF-homologue APRIL increases the proliferation of
      human malignant glioblastoma cell lines via a specific receptor.
AB  - A proliferation-inducing ligand (APRIL) of the tumour necrosis factor (TNF)
      family is produced in small amounts in many tissues and more abundantly in
      tumours. APRIL has been reported to promote cell growth in vivo and in vitro. It
      was recently shown that the production of APRIL in some glioblastoma cell lines
      does not lead to an increase in cell growth. In this study, we investigated the
      production of APRIL and its ability to increase the proliferation of eight human
      glioblastoma cell lines. We found that APRIL was produced in the eight human
      glioblastoma cell lines tested but not in the normal embryonic astrocyte
      counterparts of glioblastomas. Flow cytometry demonstrated the presence of a
      specific APRIL-binding receptor on the cell surface in all the glioblastoma cell
      lines tested. This receptor was also present on normal embryonic and adult
      astrocytes and embryonic neural progenitor cells. Moreover, the addition of
      recombinant human APRIL resulted in an increase in proliferation rate of normal
      adult astrocytes and in four of eight cell lines tested. Addition of the soluble
      recombinant TNF-receptor-homologue B-cell maturation (BCMA) chimeric protein,
      which binds APRIL, confirmed the involvement of APRIL in the growth of malignant
      glioblastoma cell lines.

PMID- 14691453
TI  - Methylation of the retinoid response gene TIG1 in prostate cancer correlates with
      methylation of the retinoic acid receptor beta gene.
AB  - Methylation of CpG islands and associated gene silencing may lead to malignant
      progression, but the mechanisms of CpG island methylation in cancer are unknown.
      The tazarotene-induced gene 1 (TIG1), also known as retinoid acid (RA) receptor
      responsive 1 gene was first identified as an RA-responsive gene and was shown to
      be downregulated in prostate cancer. Here, we show that this downregulation is
      caused by the methylation of the promoter and CpG island of TIG1. TIG1 was
      methylated in 26 of 50 (52%) primary prostate cancers, but was not methylated in
      normal tissues or benign hyperplasias. Three of four tumors that metastasized,
      five of six that were poorly differentiated and all that were assigned a Gleason
      score higher than 8 (7/7) were methylated in the promoter of TIG1. The samples
      with peripheral invasion were more frequently methylated (21/32, 66%) than
      tissues without peripheral invasion (5/18, 28%). In addition, Gleason 7-10
      cancers (21/30, 70%) were significantly more frequently methylated compared with
      Gleason 4-6 cancers (4/18, 22%) (P<0.01). The retinoic acid receptor beta (RAR
      beta) gene was frequently methylated as well (42/50, 84%). When TIG1 showed
      methylation, RAR-beta was also methylated (25/26 samples). In almost all samples
      where RAR-beta was not methylated, TIG1 was also in an unmethylated state (14/15
      samples). The methylation of TIG1 and RAR-beta was positively correlated (r=0.35;
      P=0.017). It is possible that the methylation of the retinoid response gene TIG1
      occurred in response to the methylation and inactivation of RAR-beta. These
      observations may contribute to our understanding of mechanistic events leading to
      CpG island methylation in cancer.

PMID- 14691454
TI  - Immunological and pathobiological roles of fibulin-1 in breast cancer.
AB  - Fibulin-1 (Fbln-1) is an immunogenic breast cancer-related glycoprotein
      identified by serological analysis of cDNA expression library (SEREX) strategy.
      Here, we show that dendritic cells from two breast cancer patients elicited a
      CD4(+)-mediated T-cell response to Fbln-1 presentation. In both patients, an
      antibody response to Fbln-1 was also found. By contrast, a Fbln-1-seronegative
      patient and a weakly seropositive patient demonstrated no such T-cell response.
      Analysis of human breast cancers for Fbln-1 RNA and protein expression revealed
      the presence of Fbln-1C and -1D variants. Fbln-1 was detected in the cytoplasm
      and at the cell surface of different human breast carcinoma cell lines.
      Immunohistochemical analysis of 528 archival primary breast carcinomas showed the
      expression of Fbln-1 in 35% of the cases. When the immunohistochemical findings
      were compared against pathobiological information associated with each specimen,
      an inverse relationship between Fbln-1 and cathepsin D expression was observed
      (P=0.04). Furthermore, even though long-term survival was similar between Fbln-1
      positive and -negative cases, the survival of Fbln-1-positive cases improved when
      a lymphoid infiltrate was present at the tumour site. Taken together, our
      findings of an Fbln-1-specific immunity and the improved survival associated with
      Fbln-1 expression in the presence of lymphoid infiltration point to a role of
      Fbln-1 in tumour immunosurveillance.

PMID- 14691455
TI  - NGF activation of TrkA decreases N-myc expression via MAPK path leading to a
      decrease in neuroblastoma cell number.
AB  - In neuroblastoma (NB), expression of the TrkA receptor is correlated with good
      prognosis while N-myc amplification is correlated with poor prognosis. Decreased
      N-myc levels are key to controlling growth and inducing differentiation in NB
      cells. In this report, we detail mechanisms by which nerve growth factor (NGF)
      decreases N-myc levels in TrkA-transfected NB cells and its effect on NB cell
      proliferation. NGF induced a decrease in N-myc mRNA within 1 h of treatment that
      occurred in the presence of cycloheximide. The stability of N-myc mRNA was not
      affected by NGF, indicating a transcriptional control of N-myc mRNA by NGF. NGF
      but not brain-derived neurotrophic factor (BDNF) decreased N-myc levels
      demonstrating that p75 alone was not involved. The NGF-induced decrease in N-myc
      expression was blocked by the Trk tyrosine kinase (TK) antagonist K252a
      indicating that signals transduced by Trk TK downstream targets were involved.
      Pharmacologic inhibitors implicated the mitogen-activated protein kinase (MAPK)
      path. This was supported by the finding that expression of a constitutively
      activated component of the MAPK path, MAPK kinase (MEK), decreased N-myc levels.
      Alterations in the level of N-myc are known to alter NB cell cycle progression by
      affecting the levels of E2Fs and p27(kip1). Consistent with these findings, NGF
      decreased NB cell number and decreased cyclin E-dependent kinase activity via an
      increase in p27(kip1). Thus, our results indicate that the MAP kinase is
      selectively involved in the NGF-induced N-myc downregulation through a
      transcriptional mechanism. Furthermore, NGF affects the time required for 15N
      TrkA cells to complete a replication cycle by decreasing N-myc, E2Fs, cyclin E
      kinase activity and increasing p27(kip1) binding to cyclin E kinase.

PMID- 14691456
TI  - Identification of a human glioma antigen, SOX6, recognized by patients' sera.
AB  - To identify tumor antigens for glioma, a human testis cDNA library was screened
      by serological identification of antigens by recombinant expression cloning with
      sera from glioma patients. In this screening, the most frequently isolated
      antigen was SOX6, an Sry-related high-mobility group (HMG) box-containing gene.
      SOX6 is a transcriptional factor that is specifically expressed in the developing
      central nervous system and in the early stages of chondrogenesis in mouse
      embryos. IgG antibodies against SOX6 were detected in sera from 12 of 36 glioma
      patients (33.3%), 0 of 14 patients with other brain disease (0%), and one of 54
      other cancer patients (1.9%). In sera from 37 healthy individuals, no IgG
      responses against SOX6 were detected, except in an elderly female. Furthermore,
      Western blot and ELISA analyses with sera from glioma patients revealed that the
      DNA-binding domain, the HMG box of SOX6, might be a dominant epitope of IgGs
      against SOX6. RT-PCR and Northern blot analysis revealed that the SOX6 gene was
      more highly expressed in glioma tissues than in normal adult tissues, except
      testis. Western blot analysis with an anti-SOX6 antibody demonstrated that the
      SOX6 protein was expressed in glioma tissues, but not in normal adult brain
      tissue. Immunohistochemical analysis with the anti-SOX6 antibody showed that all
      the glioma tissues analysed expressed SOX6 in tumor cells, but only a few SOX6
      positive cells were detected in non-neoplastic tissues from the cerebral cortex.
      In summary, these results indicate that the developmentally regulated
      transcription factor SOX6 is aberrantly expressed in glioma and specifically
      recognized by IgGs from glioma patients' sera.

PMID- 14691457
TI  - Overexpression of the amplified Pip4k2beta gene from 17q11-12 in breast cancer
      cells confers proliferation advantage.
AB  - Gene amplification is common in solid tumors and is associated with adverse
      prognosis, disease progression, and development of drug resistance. A small
      segment from chromosome 17q11-12 containing the HER-2/Neu gene is amplified in
      about 25% of breast cancer. HER-2/Neu amplification is associated with adverse
      prognosis and may predict response to chemotherapy and hormonal manipulation.
      Moreover, HER-2/Neu amplification may select patients for anti-HER-2/Neu-based
      therapy with Herceptin. We and others recently described a common sequence
      element from the HER-2/Neu region that was amplified in breast cancer cells. In
      addition, most, if not all, of the amplified genes from this region display
      overexpression. This raises the intriguing possibility that genes immediately
      adjacent to HER-2/Neu may influence the biological behavior of breast cancer
      carrying HER-2/Neu amplification and serve as rational targets for therapy. By
      extracting sequence information from public databases, we have constructed a
      contig in bacterial artificial chromosomes (BACs) that extends from HER-2/Neu to
      a phosphotidylinositol phosphate kinase (PIPK), Pip4k2beta from 17q11-12.
      Although a role of PI-3-kinase and AKT in cancer biology has been previously
      described, PIPK has not been previously implicated. We show that Pip4k2beta,
      initially known as Pip5k2beta, is amplified in a subset of breast cancer cell
      lines and primary breast cancer samples that carry HER-2/Neu amplification. Out
      of eight breast cancer cell lines with HER-2/Neu amplification, three have
      concomitant amplification of the Pip4k2beta gene--UACC-812, BT-474 and ZR-75-30.
      Similarly, two out of four primary breast tumors with HER-2/Neu amplification
      carry Pip4k2beta gene amplification. Intriguingly, one tumor displays an increase
      in the gene copy number of Pip4k2beta that is significantly more than that of HER
      2/Neu. Moreover, dual color FISH reveals that amplified Pip4k2beta gene may exist
      in a distinct structure from that of HER-2/Neu in ZR-75-30 cell line. These
      studies suggest that Pip4k2beta may reside on an amplification maximum distinct
      from that of HER-2/Neu and serve as an independent target for amplification and
      selective retention. Pip4k2beta amplification is associated with overexpression
      at the RNA and protein level in breast cancer cell lines. Stable expression of
      Pip4k2beta in breast cancer cell lines with and without HER-2/Neu amplification
      increases cell proliferation and anchorage-independent growth. The above
      observations implicate Pip4k2beta in the development and/or progression of breast
      cancer. Our study suggests that Pip4k2beta may be a distinct target for gene
      amplification and selective retention from 17q11-12.

PMID- 14691458
TI  - The zinc-finger transcription factor GLI2 antagonizes contact inhibition and
      differentiation of human epidermal cells.
AB  - In stratified epidermis, activation of the Hh/Gli signal transduction pathway has
      been implicated in the control of cell proliferation and tumorigenesis. The zinc
      finger transcription factor Gli2 has been identified as critical mediator of the
      Hh signal at the distal end of the pathway, but the molecular mechanisms by which
      Gli2 regulates cell proliferation or induces epidermal malignancies such as basal
      cell carcinoma are still unclear. Here, we provide evidence for a role of human
      GLI2 in antagonizing contact inhibition and epidermal differentiation. We show by
      gene expression profiling that activation of the GLI2 oncogene in human
      keratinocytes activates the transcription of a number of genes involved in cell
      cycle progression such as E2F1, CCND1, CDC2 and CDC45L, while it represses genes
      associated with epidermal differentiation. Analysis of the proliferative effect
      of GLI2 revealed that GLI2 is able to induce G1-S phase progression in contact
      inhibited keratinocytes. Detailed time-course experiments identified E2F1 as
      early transcriptional target of GLI2. Further, we show that GLI2 expression in
      human keratinocytes results in a marked downregulation of epidermal
      differentiation markers. The data suggest a role for GLI2 in Hh-induced epidermal
      neoplasia by opposing epithelial cell cycle arrest signals and epidermal
      differentiation.

PMID- 14691459
TI  - A ligand-inducible anaplastic lymphoma kinase chimera is endocytosis impaired.
AB  - Ligand-induced membrane trafficking of the anaplastic lymphoma kinase (ALK) was
      studied using a chimeric receptor in which the extracellular and transmembrane
      domain of ALK was substituted for the corresponding regions of epidermal growth
      factor receptor (EGFR). Wild-type EGFR, EGFR/ALK and an EGFR/ALK kinase negative
      mutant were independently expressed in mouse NR6 fibroblasts. The capacity of
      EGFR/ALK to mediate [125I]-EGF internalization, receptor degradation and
      downregulation, which has never been previously described, was assayed. The rate
      of [125I]-EGF-induced internalization mediated by the cytoplasmic domain of ALK
      was reduced several fold compared with the wild-type EGFR. The low rate of EGF
      internalization promoted by EGFR/ALK correlated with an impaired degradation and
      downregulation of the receptor and indicate that ALK is not subject to
      traditional mechanisms used to regulate receptor tyrosine kinase function.
      Accordingly, ALK-activated intracellular domain does not associate in vivo with c
      cbl and does not undergo ligand-mediated ubiquitination. The current study
      provides new insight into the function and regulation of ALK suggesting that the
      relative long membrane residence of activated ALK might confers a more potent and
      prolonged signaling activity. Indeed NR6-EGFR/ALK cells exhibited a approximately
      3-fold increase in a maximal mitogenic response than NR6-EGFR.

PMID- 14691460
TI  - TAT-apoptin is efficiently delivered and induces apoptosis in cancer cells.
AB  - Apoptin has been described to induce apoptosis in various human cancer cell
      lines, but not in normal cells, thus making it an interesting candidate for the
      development of novel therapeutic strategies. Apoptin was generated and cloned
      into several mammalian expression vectors. Transfection or microinjection of
      apoptin cDNA resulted in its expression, initially in the cytoplasm with a
      filamentous pattern. Subsequently, apoptin entered the nucleus and efficiently
      induced apoptosis in several cancer cell lines. Nuclear localization was shown to
      be required for induction of apoptosis. Apoptin expression level was found to be
      an important determinant of the efficiency of induction of apoptosis.
      Surprisingly, expression of apoptin or GFP-apoptin cDNA induced apoptosis in some
      normal cells. When fused to the HIV-TAT protein transduction domain and delivered
      as a protein, TAT-apoptin was transduced efficiently (>90%) into normal and
      tumour cells. However, TAT-apoptin remained in the cytoplasm and did not kill
      normal 6689 and 1BR3 fibroblasts. In contrast TAT-apoptin migrated from the
      cytoplasm to the nucleus of Saos-2 and HSC-3 cancer cells resulting in apoptosis
      after 24 h. This study shows that apoptin is a powerful apoptosis-inducing
      protein with a potential for cancer therapy.

PMID- 14691461
TI  - Impact of the nuclear receptor coactivator AIB1 isoform AIB1-Delta3 on estrogenic
      ligands with different intrinsic activity.
AB  - The nuclear receptor coactivator amplified in breast cancer 1 (AIB1) and its more
      active isoform AIB1-Delta3 are overexpressed in breast cancer and preneoplastic
      breast tissue. However, the impact of these proteins on the transcriptional
      activity of natural estrogens or selective estrogen receptor modulators (SERMs)
      has not been determined. Here we show that AIB1-Delta3 causes a significant
      increase in the efficacy of 17beta-estradiol at both estrogen receptor-alpha (ER
      alpha) and ER-beta in ovarian, breast and endometrial cancer cell lines. AIB1
      Delta3 also significantly increased the efficacy of the natural estrogen
      genistein at both ER-alpha and ER-beta, whereas AIB1 had no effect on either the
      potency or efficacy of genistein at either receptor. The estrogenic efficacy of
      the partial agonist tamoxifen was significantly increased in all cell lines at ER
      alpha by overexpression of AIB1-Delta3 both on transfected and endogenous
      estrogen responsive genes. In contrast, overexpression of AIB1 or AIB1-Delta3 had
      no effect on the potency or efficacy of the SERM raloxifene. We conclude that
      overexpression of the AIB1-Delta3 isoform will increase the estrogenicity of a
      variety of natural and pharmacologic compounds in tissues that develop hormone
      dependent neoplasias and overexpression of these cofactors may be a contributing
      factor to the hormone-driven development of neoplasia and to antiestrogen
      resistance of breast cancers.

PMID- 14691478
TI  - Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear
      cytoplasmic shuttling of PPAR-gamma and RelA.
AB  - The human gut microflora is important in regulating host inflammatory responses
      and in maintaining immune homeostasis. The cellular and molecular bases of these
      actions are unknown. Here we describe a unique anti-inflammatory mechanism,
      activated by nonpathogenic bacteria, that selectively antagonizes transcription
      factor NF-kappaB. Bacteroides thetaiotaomicron targets transcriptionally active
      NF-kappaB subunit RelA, enhancing its nuclear export through a mechanism
      independent of nuclear export receptor Crm-1. Peroxisome proliferator activated
      receptor-gamma (PPAR-gamma), in complex with nuclear RelA, also undergoes
      nucleocytoplasmic redistribution in response to B. thetaiotaomicron. A decrease
      in PPAR-gamma abolishes both the nuclear export of RelA and the anti-inflammatory
      activity of B. thetaiotaomicron. This PPAR-gamma-dependent anti-inflammatory
      mechanism defines new cellular targets for therapeutic drug design and
      interventions for the treatment of chronic inflammation.

PMID- 14691479
TI  - Entry is a rate-limiting step for viral infection in a Drosophila melanogaster
      model of pathogenesis.
AB  - The identification of host factors that control susceptibility to infection has
      been hampered by a lack of amenable genetic systems. We established an in vivo
      model to determine the host factors that control pathogenesis and identified
      viral entry as a rate-limiting step for infection. We infected Drosophila
      melanogaster cells and adults with drosophila C virus and found that the clathrin
      mediated endocytotic pathway is essential for both infection and pathogenesis.
      Heterozygosity for mutations in genes involved in endocytosis is sufficient to
      protect flies from pathogenicity, indicating the exquisite sensitivity and
      dependency of the virus on this pathway. Thus, this virus model provides a
      sensitive and efficient approach for identifying components required for
      pathogenesis.

PMID- 14691480
TI  - Gadd45beta is important for perpetuating cognate and inflammatory signals in T
      cells.
AB  - Gadd45beta (growth arrest and DNA damage-inducible, beta) is involved in cell
      cycle arrest, apoptosis, signal transduction and cell survival. In T cells,
      Gadd45b was rapidly induced by T cell receptor (TCR) and inflammatory signals.
      Deficiency of Gadd45beta in CD4+ T cells impaired their responses to TCR
      stimulation or inflammatory cytokines. ERK, p38 and JNK activation were all
      substantially suppressed in Gadd45beta-deficient CD4+ T cells. Cytokine
      production by Gadd45beta-deficient CD4+ T cells was also impaired. Furthermore,
      Gadd45beta mediated inflammatory cytokine production by dendritic cells, and
      Gadd45beta-deficient mice showed an impaired T helper type 1 response during
      Listeria monocytogenes infection. Gadd45beta is therefore a critical feedback
      regulator that perpetuates both cognate and inflammatory signals.

PMID- 14691481
TI  - The extracellular matrix protein mindin is a pattern-recognition molecule for
      microbial pathogens.
AB  - Microbial pathogens use a variety of their surface molecules to bind to host
      extracellular matrix (ECM) components to establish an effective infection.
      However, ECM components can also serve as an integral part of the innate
      immunity. Mice lacking expression of mindin (spondin 2), a highly conserved ECM
      protein, have an impaired ability to clear bacterial infection, and mindin
      deficient macrophages show defective responses to a broad spectrum of microbial
      stimuli. Moreover, mindin binds directly to bacteria and their components and
      functions as an opsonin for macrophage phagocytosis of bacteria. Thus, mindin is
      essential in the initiation of the innate immune response and represents a unique
      pattern-recognition molecule in the ECM for microbial pathogens.

PMID- 14691482
TI  - An essential function for the nuclear receptor RORgamma(t) in the generation of
      fetal lymphoid tissue inducer cells.
AB  - Lymphoid tissue inducer (LTi) cells are associated with early development of
      lymph nodes and Peyer's patches. We show here that during fetal life the nuclear
      hormone receptor RORgamma(t) is expressed exclusively in and is required for the
      generation of LTi cells. RORgamma(t+) LTi cells provide essential factors, among
      which lymphotoxin-alpha1beta2 is necessary but not sufficient for activation of
      the mesenchyma in lymph node and Peyer's patch anlagen. This early LTi cell
      mediated activation of lymph node and Peyer's patch mesenchyma forms the
      necessary platform for the subsequent development of mature lymphoid tissues.

PMID- 14691483
TI  - [Less money--but perhaps richer?].

PMID- 14691484
TI  - [Birth, parturition and rituals].

PMID- 14691485
TI  - [Heroin as an analgesic].

PMID- 14691486
TI  - [Heroin: a useful analgesic?].
AB  - BACKGROUND: In some countries, heroin is widely used as an analgesic agent.
      MATERIAL AND METHODS: The literature describing the history, pharmacology and
      analgesic use of heroin was reviewed. RESULTS: Heroin is a semi-synthetic
      morphine derivative. A century ago it was considered a panacea with numerous
      indications. Today it is best known as a drug of abuse, but is still in use as an
      analgesic. Most studies that compare heroin with other analgesics have
      methodological shortcomings; however, they generally indicate that heroin has a
      clinical effect not very different from morphine. An better aqueous solubility as
      compared to morphine may in some situations be advantageous. Because of a
      proposed incomplete cross-tolerance between heroin and other opioid analgesics,
      it may be used if the patient shows sub-therapeutic response to first-line
      opioids. INTERPRETATION: Although not well documented, heroin appears to be an
      effective analgesic with certain properties different from those of morphine. It
      may be of clinical value in conditions with acute and/or terminal pain.

PMID- 14691487
TI  - [Hospital admissions for acute asthma in children].
AB  - BACKGROUND: Monitoring hospital admissions for acute asthma may give information
      regarding prevalence, severity and treatment of childhood asthma. In a
      retrospective population-based study, the medical records were studied for
      children aged one to 14 years admitted for asthma during four periods, each of
      two years, from 1984 to 2000. RESULTS: Children aged one and two had the highest
      admission rates; both primary admission and re-admissions increased substantially
      throughout the period. For children aged three and four, total admission rates
      went up during the 1980s, but were down again during the 1990s. For older
      children there was a tendency towards declining admission rates over the study
      period. The use of systemic steroids at admission and pre-hospital inhaled
      corticosteroids increased substantially over the period. INTERPRETATION: For one
      and two-year-old children there was a continuous increase in both primary and
      readmission rates. Given better pre-hospital treatment there is a potential for
      lowering admission rates.

PMID- 14691488
TI  - [Interventional radiology in Norwegian hospitals].
AB  - BACKGROUND: In recent years, interventional radiology has gained in importance in
      patient treatment. In order to assess the impact of this trend, the executive
      committee of the Norwegian Society for Interventional Radiology made a
      registration of all interventional procedures in Norwegian hospitals in the year
      2000. MATERIAL AND METHODS: Data were collected by a questionnaire sent to all
      Norwegian hospitals. Coronary interventions were not included. RESULTS: Forty
      four out of 58 departments returned the questionnaire; 33 stated that they
      performed interventional procedures. A total of 18 135 procedures were performed
      in Norway in 2000; we present data on the distribution of types of procedures on
      different categories of hospitals. INTERPRETATION: A large number of
      interventional radiological procedures were performed in Norwegian hospitals in
      the year 2000, types of intervention that are considered very important in
      patient management in small hospitals, too.

PMID- 14691489
TI  - [To study medicine--a threat to women's health?].
AB  - 110 years have passed since the first woman graduated in medicine in Norway.
      Marie Spangberg, married name Holth, (1865-1942) qualified in 1893, exactly 80
      years after the Faculty of Medicine had been established in the first Norwegian
      university. The debates ahead of the decision to admit women to Academia were
      violent and the resistance considerable. In retrospect the protest from the
      faculty of medicine has been considered one of the most prejudiced statements of
      its time on women's nature. It is, however, a brilliant illustration of the
      establishment's view on the gender question. Marie Spangberg was an extraordinary
      woman. In order to reach her goals she had three barriers to pass. First, by
      studying medicine she passed the gender barrier. Second, as the daughter of a
      poor watchmaker's widow she moved up the social ladder. Third, as hospital
      physicians closed their gates to female colleges, she had to go abroad for her
      specialisation. Her education represented considerable social and cultural
      advancements. Marie Spangberg did not engage in the feminist movement, but she
      supported the battle and was fully aware that she enjoyed the fruits of other
      women's battle for freedom.

PMID- 14691490
TI  - [A polar expedition in challenging circumstances--experiences and psychological
      reactions].
AB  - Four men, in the company of 16 dogs, skied for five weeks from Gasefjord to Ellef
      Ringnes Land, North Canada. The expedition met with considerable unforeseen
      challenges such as extreme and prolonged cold, unmotivated Greenland dogs, and
      much pack ice. Psychological reactions were described and measured by a
      qualitative free text analysis and a test battery including GHQ-30 (General
      Health Questionnaire) and STAI State (State-Trait Anxiety Inventory) before,
      during, and after the expedition. Five main themes were found: external
      influences, relations between men and animals, progress and expectations,
      interpersonal relations, and thoughts at the end of the expedition. Negative
      emotional reactions were mostly present at the beginning of the expedition and
      were related to the environment and the pressure of perceived expectations from
      the outside world. Frustrations were enhanced by forced inactivity. Perceived
      essential positive elements were a strong group identity and friendship. The
      acceptance of dissension was low; the group strived to achieve consensus before
      decisions were made. The psychometric results showed more stress and anxiety
      immediately before the expedition than after. These parameters also increased
      significantly at the beginning of the expedition, then there was a reverse. The
      level of anxiety was higher in the two leaders. The expedition was concluded in
      an overall atmosphere of mutual affection, satisfaction, and pride.

PMID- 14691491
TI  - [Increased cortisol levels, frostbite and effects on the muscles and skeleton
      during extreme polar conditions].
AB  - BACKGROUND: We wanted to record physiological changes, injuries and illnesses
      during a long sledge expedition in North Canada. MATERIAL AND METHODS: The
      expedition consisted of four men aged 41 to 50, and 16 polar dogs. Measurements
      of cortisol in saliva were performed before, during and after the expedition.
      Frostbites and other injuries were registered continuously. Body weight and
      muscle, fat and bone mass were measured by dual X-ray absorptiometry scanning,
      and strength and endurance of shoulders, knees and back were tested. The group
      encountered extreme frost (-30 to -42 degrees C day temperature), wind,
      unexpected amounts of pack ice, and poorly motivated dogs. RESULTS AND
      INTERPRETATION: The participants showed increased free cortisol levels during
      their stay on the ice, probably because of increased mental stress. Three got
      first degree and two second-degree frostbites, but the affected areas were normal
      on vascular examination five months later. All members increased their muscle
      mass, but muscle strength and endurance remained unchanged.

PMID- 14691492
TI  - [Bipolar head injury with global amnesia].
AB  - We report the first case of bipolar head injury, that is, subsequent head
      injuries sustained near both poles of the Earth. The injury caused a true global
      amnesia with loss of memory for the journey around the globe. This case history
      illustrates how modern emergency services have reduced the hazards of polar
      exploration, and how a second impact after a primary head injury may cause life
      threatening complications.

PMID- 14691493
TI  - [The suicide of Hjalmar Johansen].
AB  - BACKGROUND: Hjalmar Johansen was one of Norway's most famous gymnasts. He joined
      Fridtjof Nansen's polar expedition with Fram in 1893 and went on ski farthermost
      north with him in 1895/96. On their return to Norway the crew was celebrated as
      heroes. MATERIAL AND METHODS: The polar literature has been reviewed and the
      author has focused on the life and suicide of Hjalmar Johansen. RESULTS AND
      INTERPRETATION: Johansen was promoted to captain in the infantry, a role he
      didn"t manage. He drank heavily and left the army. He rehabilitated during his
      stay at Spitzbergen from 1907 to 1909. In 1910 he was one of Roald Amundsen's men
      in Antarctica. Amundsen started out too early because of his race with Robert
      Scott. Johansen disagreed and rescued a member from freezing to death. A quarrel
      with Amundsen resulted in his dismissing Johansen from the party heading for the
      South Pole. This led to a vicious circle that ended in Johansen's suicide in the
      new year 1913. Hjalmar Johansen was a man of a simple and kind character who
      helped his comrades with his physical strength. A master of muscular activity he
      was without deeper self-reflecting power and needed the support of the people
      around him; without it, he was ashamed of himself.

PMID- 14691494
TI  - [The challenges for physicians on polar expeditions around the year 1900].
AB  - One century ago there was an intense activity in exploring the unknown polar
      areas. The paper gives an account of 14 expeditions involving 17 physicians. For
      several years, the official versions were those published by the leaders of the
      expeditions, the heroes. During the last years, however, the diaries of their
      companions have been published and provide valuable and rectifying information.
      Surprisingly, most of the physicians were young and inexperienced and unfit for
      the extreme strain of the polar areas.

PMID- 14691495
TI  - [Do women die from pregnancy these days?].
AB  - BACKGROUND: Our aim was to estimate the number and causes of maternal deaths in
      Norway during 1981-2000. MATERIAL AND METHODS: We collected information from
      Statistics Norway about births, maternal deaths, and causes of death. RESULTS: We
      registered 47 maternal deaths. The rate was 3.5 per 100 000 births during the
      1980s and 4.6 during the 1990s. Pregnancy-induced hypertension was the leading
      cause, accounting for 14 deaths (30%). Caesarean section and thromboembolism
      accounted for five deaths each, and four deaths were coded as postpartum sepsis.
      As opposed to the period before 1980, haemorrhage accounted for only one death.
      INTERPRETATION: Since 1980 there has been no decrease in the maternal mortality
      rate in Norway. Caesarean section was an important underlying cause of death. An
      enquiry into maternal deaths could answer whether there is a potential for
      further reduction of the maternal mortality rate, particularly from
      preeclampsia/eclampsia.

PMID- 14691496
TI  - [Change of partner between births and adverse pregnancy outcomes].
AB  - BACKGROUND: Childbearing with different fathers has increased in western
      societies because of the higher frequency of divorce and remarriage. Pregnancy
      outcomes may differ between mothers who have changed partner between first and
      second birth and mothers who have the same father for both births. Women who
      change partner may have individual characteristics that increase risk of adverse
      outcomes, but change of partner could also be associated with unfavourable
      changes in behaviour. MATERIAL AND METHODS: The Medical Birth Registry of Norway
      was established in 1967 and includes information on approximately 1.8 million
      births until 1998. Both parents are recorded. We have compared pregnancy outcomes
      for 30 176 mothers who changed partner between first and second birth and 461 154
      mothers who had the same partner for both births. RESULTS: In relation to the
      first birth, the risk of adverse pregnancy outcomes was not clearly different
      between mothers who later had a second birth with another partner and mothers who
      had the same partner for both births. Offsprings of mothers who changed partner
      between first and second birth were at higher risk of infant mortality (relative
      risk 1.5, 95 % confidence interval, 1.3-1.7), preterm birth (< 37 weeks; relative
      risk 1.3, 95 % confidence interval, 1.2-1.4), and low birth weight (< 2500 gram;
      relative risk 1.5, 95 % confidence interval, 1.4-1.6), after adjustment for
      maternal age and level of education, interval between births, and time period.
      INTERPRETATION: Mothers who change partner between first and second birth are at
      increased risk of having a preterm, low birth weight baby with increased risk of
      infant death for the second child compared to mothers who have the same partner
      for both births.

PMID- 14691497
TI  - [A watershed in Norwegian obstetrics].
AB  - BACKGROUND: Professional obstetrics in Norway developed during the 19th century.
      This paper analyses the development through the second half of the 19th century
      at the Maternity Clinic in Christiania (now Oslo). MATERIAL AND METHODS: All
      patient files from the years 1852, 1872 and 1892, a total of 1231 records, were
      analysed. Socio-demographic and gynaecologic data were registered as well as data
      about the delivery and the child. RESULTS: The number of deliveries increased
      nearly five times during the period. The proportion of married women increased
      from less than 20% to nearly 50%. Maternal mortality decreased from above 3% to
      below 1%, mostly because childbed fever became infrequent. The number of
      operative deliveries increased substantially, particularly the use of the
      obstetric forceps, in 1892 utilised in 6 % of deliveries. In the reviews
      published in those days, eclampsia and reduced contractions were the most
      frequently cited indications for the use of the obstetric forceps. Problems with
      the heart sound of the fetus were not mentioned. However, patient files
      demonstrate that a weak or missing heart sound of the fetus was also an important
      indication for the use of the forceps. INTERPRETATION: Giving birth at the clinic
      was gradually becoming an alternative for other than poor women, because it was
      safer than before and in some cases the obstetricians could offer effective help.
      However, at the end of the 19th century, not more than about 15% of all
      deliveries took place at the clinic. This paper demonstrates the importance of
      scrutinising patient files as a supplement to register data, as is the case
      today, too.

PMID- 14691498
TI  - [Postnatal care in a cross-cultural and historical perspective].
AB  - BACKGROUND: In most societies, birth and the immediate postpartum period are
      considered a time of vulnerability for mother and child. Rituals for major
      changes in the life cycle are common in most societies. The aim of this study was
      to present some examples of postpartum customs in a cross-cultural and historical
      perspective. We also present research on associations between postnatal care and
      mental health. MATERIAL AND METHODS: A systematic search was performed in Medline
      and the Science Citation Index Expanded (ISI) from 1966 until March 2003.
      Reference lists in books about pregnancy and birth from the library of the
      University of Oslo were used to get additional information. RESULTS: The
      postnatal period is defined as approximately 40 days in most cultures; most
      societies have special postnatal customs that include special diet, isolation,
      rest and help in the household. The resemblance between different cultures is
      striking. Many postnatal customs from rural societies that were common before
      1950 have disappeared. The focus on rest and help in the household for the mother
      after delivery has been reduced. INTERPRETATION: We need more knowledge about the
      impact of different kinds of postnatal care on the mother's wellbeing.

PMID- 14691499
TI  - [The "rade"disease--a Norwegian tragedy].
AB  - The rade disease (radesyken) was wide-spread particularly in southwestern Norway
      during the 18th and 19th centuries. The fight against this disease prepared the
      grounds for the public health services in this country. It was suggested that
      radesyke was a manifestation of syphilis, although with some uncommon
      epidemiological and clinical features. This paper reminds of the sufferings that
      this medical disaster inflicted on thousands of patients of all age groups during
      the 150 years of its presence in Norway. The clinical picture of radesyke is
      presented based on descriptions of 63 patients treated by Dr. Hendrich Deegen at
      the radesyke hospital in Flekkefjord in the years 1776-78. Finally, a brief
      reference is made to probable causes of the particular manifestations of this
      disease in Norway during that period.

PMID- 14691500
TI  - [The physician Hendrich Deegen and the Rade Hospital in Flekkefjord].
AB  - The physician Hendrich Deegen (1742-92) took the initiative for, was the
      architect of, and organised the building of a hospital for sufferers of radesyge
      in Flekkefjord, a small town in Norway, in 1776. He was also the hospital's first
      doctor. By describing his achievements at the hospital and his personal life in
      this town, this paper provides a sketch of a physician's daily life in late 18th
      century Norway.

PMID- 14691501
TI  - [Thoughts about the "rade" disease in Norway--"it takes its victims slowly"].
AB  - Radesyge first appeared in south-western Norway in the middle of the 18th
      century; the endemic that followed was to haunt the region for close to one
      hundred years. The disease was characterized by severe wounds, often with bone
      decomposition. The face was frequently involved, causing striking malformations.
      Radesyge was at the time considered a serious threat to society and was the
      subject of intense public debate over several decades. Core components of the
      modern health care system in Norway can trace their origin to countermeasures
      taken to combat the spread of this disease. In this article, the author argues
      that rather than viewing radesyge as an outbreak of tertiary syphilis, which has
      been the custom for the last hundred years, it should, for scholarly purposes, be
      seen as a separate event. This is the only way to properly grasp the impact of
      the endemic on patients, society, politics and science at the time.

PMID- 14691502
TI  - [William Carlos Williams--a poet of everyday life].
AB  - The physician William Carlos Williams (1883-1963) was one of the most important
      poets in USA in the 20th century. This article provides some biographical data,
      examples of his poems and extracts from his autobiography, in which he discusses
      the relationship between medical practice and poetry.

PMID- 14691504
TI  - [Gadamer's defense of the art of medicine].

PMID- 14691505
TI  - [Disease and identity--a study of The magic mountain by Thomas Mann].
AB  - Disease is more than dysfunctional organs, morphological abnormalities and
      genetic divergence. It is also about existence, self-conception and social
      identity. Disease changes us as persons, but how this happens is usually not
      discussed in medical textbooks. However, literature appears to be rich in
      descriptions of these perspectives. This article explores The magic mountain by
      Thomas Mann to elucidate the relationship between personal identity and disease.
      I will argue that such knowledge is important to modern clinical practice.

PMID- 14691506
TI  - ["Dead in December...to an applause"--a biographic sketch of W.A.Mozart].

PMID- 14691507
TI  - [Back to Hippocrates?].

PMID- 14691508
TI  - [Dr Stockmann and Dr Snow--two heroes of public health].
AB  - Dr Thomas Stockmann, the main character of An enemy of the people by Henrik Ibsen
      (1828-1906), has been described as a hero of public health. In spite of his
      idealism and high principles, he was, however, not able to do anything about the
      contaminated water supply of the baths in the town where he lived. Important
      differences may be noticed if we compare the fictional Dr Stockmann with Dr John
      Snow (1813-58), a real hero of public health famous for his handling of a cholera
      epidemic in London in 1854. While Dr Snow carried out extensive investigations of
      the relation between water supply and illness and still was humble when
      presenting his findings, the fictional Dr Stockmann took only one sample of water
      for examination and was bombastic in his conclusion. And while Dr Snow had a
      simple suggestion for solving the problem, Dr Stockmann seemed more eager to
      dramatize the situation. Scientific documentation and a practical attitude to
      problem solving continue to be important in order to achieve results in the field
      of public health.

PMID- 14691509
TI  - [Sigmund Freud, the unconscious and the study of human being].

PMID- 14691510
TI  - [Marianne in hospital].
AB  - In 1948 Norwegian architect and author Odd Brochmann (1909-92) published his
      popular children's book Marianne in hospital (Marianne pa sykehus). Two years
      later the book was filmed on the initiative of the Ministry of Social Affairs.
      This article considers the question of what were the purposes of the film.
      Officially, it was presented as an attempt to teach children not to be afraid of
      hospitals. However, in internal notes and letters the health authorities stressed
      that the film should be an educational film about the social benefits and health
      services of the welfare state. Furthermore, I will argue that the film was the
      result of a wish to present the nation's modern hospital care and, by way of
      conclusion, discuss the characterisation of the film as educational.

PMID- 14691511
TI  - [Skeletons in the cupboard--treatment of Arne Torkildsen].
AB  - Arne Torkildsen (1899-1968) developed Torkildsen's operation, the first
      successful shunt operation treating increased intraventricular pressure in the
      brain. He defended his doctoral thesis "Ventriculo-cisternostomy" in the
      University of Copenhagen in 1950, a thesis that had been rejected by the
      University of Oslo in his home country Norway. He was not found qualified for the
      post of associate professor in neurosurgery in spite of being recommended by two
      international adjudicating committees on four occasions. Torkildsen was accused
      of having misled the university by omitting one third of the operated patients
      from his thesis. No-one actually called him a cheat, but tales of cheating and
      infighting between colleagues aspiring to the same academic posts leave a
      confusing picture. This paper sums up the story and the possible motives
      different actors might have had for trying to promote or stop Torkildsen's
      academic career.

PMID- 14691512
TI  - [A Norwegian cancer researcher honoured by a memorial].

PMID- 14691513
TI  - [Peter Herman Barclay--a Norwegian physician in the West Indies in the 1820s].
AB  - When Peter Herman Barclay (1781-1833), a Norwegian of Scottish descent was
      sixteen, he went to Copenhagen for his medical education, during which he
      suffered from illness and financial distress. He qualified as a surgeon and,
      during the Napoleonic Wars, served with the Danish and French navies (allies at
      the time) and in the land campaigns in Holland and France. This article describes
      Barclay's experience as a surgeon on the Virgin Islands of St. Thomas and St.
      Johns in the 1820s. These islands were under Danish jurisdiction from 1755 to
      1917, at which time they were sold to the USA. Barclay had a hospital with 40
      beds at his disposal. He observed various infectious diseases and the efficacy of
      his treatments. An experienced surgeon, he did not hesitate to trepan or
      amputate. He used Hagedorn's apparatus for fractures of the hip and a French
      caustics treatment for strictures of the urethra. Barclay wrote about his
      experience in Bibliothek for Laeger, a medical journal, and in a book published
      in 1830.

PMID- 14691514
TI  - [Improved medicine lists with multi-dose packaging?].
AB  - BACKGROUND: In a part of Oslo, Norway, the community care services use multi-dose
      packed medicines for some of their clients. We wanted to investigate whether this
      improved quality as compared to manually dispensed medicines. MATERIAL AND
      METHODS: We included 20 patients who received multi-dose packaged medicines, and
      33 patients in two other districts who received manually dispensed medicines, and
      recorded disagreements between what daily medicines the general practitioner had
      prescribed and those that were dispensed by the community care service or the
      multi-dose packager. RESULTS: The 53 patients received a total of 324 daily
      medicines. Disagreements were found in 23% of all daily medicines, involving 58%
      of patients. In addition, deficiencies in the information on medication were
      found in 6% of all daily doses. For patients who received multi-dose packaged
      medicines, disagreements were found in relation to 21 % of the drugs. For
      patients who received manually dispensed medicines, disagreements were found in
      17% and 33% of the medicines lists in the two districts. INTERPRETATION: The
      disagreements found between the medication prescribed by doctors and what was
      dispensed were unacceptable regardless of dispensing method (manual or
      automatic). It is important to clarify who should be responsible for maintaining
      accurate records for patients who receive community care.

PMID- 14691515
TI  - [Erroneous drug charts--a health hazard?].
AB  - BACKGROUND: For appropriate medical attention to be given to patients in
      community care it is essential that the drug charts of the community nurse and
      the general practitioner's patient records correspond. MATERIAL AND METHODS: We
      compared the drug charts for all 38 patients treated by the community nurse in
      one geographically defined area whose defined general practitioner worked at a
      health centre in Trondheim, Norway. We calculated total, proportional and chance
      corrected agreement (Cohen's kappa) for the number of drugs within these records.
      RESULTS: We found that 90% of the drug charts differed by one or more drugs. The
      general practitioner prescribed 207 drugs of which the patients received only
      149, hence 61 prescribed drugs "disappeared". The community nurse administered
      201 drugs; this implies that 51 came from other services than the general
      practitioner. Overall agreement was 53%, chance corrected agreement was kappa =
      0.29 (95% confidence interval: 0.12-0.47). INTERPRETATION: The number of drugs in
      the patient records of the community nurse and the general practitioner differ
      substantially. We find systematic errors in the drug charts and conclude that
      such errors may be a potential health hazard for the patients.

PMID- 14691516
TI  - [Patient experiences in Norwegian hospitals--changes over time?].
AB  - BACKGROUND: Patient experience has been identified as a national indicator of
      hospital quality. We describe the changes in patient experiences 1996-2000 for
      seven Norwegian hospitals. MATERIAL AND METHODS: A patient experience
      questionnaire was sent to medical and surgical patients in a stratified random
      sample of hospitals in 1996. The same questionnaire was used in similar surveys
      in 1998 and 2000. Responses from hospital wards included in all three surveys
      were compared on ten summated rating scales. Changes were identified by multiple
      linear regression. RESULTS: Responses from a total of 10 600 patients were
      analysed. For six scales no change was noted: general satisfaction, information
      on medication, information on examinations, nursing services, doctor services,
      and organization. Statistically significant improvement was found for three
      indices: communication, contact with next-of-kin, and information regarding
      future complaints. For one scale, scores changed for the worse: hospital and
      equipment. All changes were small. INTERPRETATION: Patient experiences with
      Norwegian hospitals did not change much between 1996 and 2000. On some indices,
      our data indicate slight improvement. Patient assessment of buildings and
      equipment changed negatively.

PMID- 14691517
TI  - [Should patients do what their physicians say?].

PMID- 14691523
TI  - [Sexual abuse of children].

PMID- 14691525
TI  - [Mentally traumatised].

PMID- 14691527
TI  - [Marked increase of the number of myocardial infarctions].

PMID- 14691529
TI  - [Adverse effects--making nail soup or nailing the coffin?].

PMID- 14691532
TI  - A wingless flight.

PMID- 14691533
TI  - Mechanism for multiple ligand recognition by the human transferrin receptor.
AB  - Transferrin receptor 1 (TfR) plays a critical role in cellular iron import for
      most higher organisms. Cell surface TfR binds to circulating iron-loaded
      transferrin (Fe-Tf) and transports it to acidic endosomes, where low pH promotes
      iron to dissociate from transferrin (Tf) in a TfR-assisted process. The iron-free
      form of Tf (apo-Tf) remains bound to TfR and is recycled to the cell surface,
      where the complex dissociates upon exposure to the slightly basic pH of the
      blood. Fe-Tf competes for binding to TfR with HFE, the protein mutated in the
      iron-overload disease hereditary hemochromatosis. We used a quantitative surface
      plasmon resonance assay to determine the binding affinities of an extensive set
      of site-directed TfR mutants to HFE and Fe-Tf at pH 7.4 and to apo-Tf at pH 6.3.
      These results confirm the previous finding that Fe-Tf and HFE compete for the
      receptor by binding to an overlapping site on the TfR helical domain. Spatially
      distant mutations in the TfR protease-like domain affect binding of Fe-Tf, but
      not iron-loaded Tf C-lobe, apo-Tf, or HFE, and mutations at the edge of the TfR
      helical domain affect binding of apo-Tf, but not Fe-Tf or HFE. The binding data
      presented here reveal the binding footprints on TfR for Fe-Tf and apo-Tf. These
      data support a model in which the Tf C-lobe contacts the TfR helical domain and
      the Tf N-lobe contacts the base of the TfR protease-like domain. The differential
      effects of some TfR mutations on binding to Fe-Tf and apo-Tf suggest differences
      in the contact points between TfR and the two forms of Tf that could be caused by
      pH-dependent conformational changes in Tf, TfR, or both. From these data, we
      propose a structure-based model for the mechanism of TfR-assisted iron release
      from Fe-Tf.

PMID- 14691534
TI  - Pten dose dictates cancer progression in the prostate.
AB  - Complete inactivation of the PTEN tumor suppressor gene is extremely common in
      advanced cancer, including prostate cancer (CaP). However, one PTEN allele is
      already lost in the vast majority of CaPs at presentation. To determine the
      consequence of PTEN dose variations on cancer progression, we have generated by
      homologous recombination a hypomorphic Pten mouse mutant series with decreasing
      Pten activity: Pten(hy/+) > Pten(+/-) > Pten(hy/-) (mutants in which we have
      rescued the embryonic lethality due to complete Pten inactivation) > Pten
      prostate conditional knockout (Pten(pc)) mutants. In addition, we have generated
      and comparatively analyzed two distinct Pten(pc) mutants in which Pten is
      inactivated focally or throughout the entire prostatic epithelium. We find that
      the extent of Pten inactivation dictate in an exquisite dose-dependent fashion
      CaP progression, its incidence, latency, and biology. The dose of Pten affects
      key downstream targets such as Akt, p27(Kip1), mTOR, and FOXO3. Our results
      provide conclusive genetic support for the notion that PTEN is haploinsufficient
      in tumor suppression and that its dose is a key determinant in cancer
      progression.

PMID- 14691535
TI  - Identification of Drosophila MicroRNA targets.
AB  - MicroRNAs (miRNAs) are short RNA molecules that regulate gene expression by
      binding to target messenger RNAs and by controlling protein production or causing
      RNA cleavage. To date, functions have been assigned to only a few of the hundreds
      of identified miRNAs, in part because of the difficulty in identifying their
      targets. The short length of miRNAs and the fact that their complementarity to
      target sequences is imperfect mean that target identification in animal genomes
      is not possible by standard sequence comparison methods. Here we screen conserved
      3' UTR sequences from the Drosophila melanogaster genome for potential miRNA
      targets. The screening procedure combines a sequence search with an evaluation of
      the predicted miRNA-target heteroduplex structures and energies. We show that
      this approach successfully identifies the five previously validated let-7, lin-4,
      and bantam targets from a large database and predict new targets for Drosophila
      miRNAs. Our target predictions reveal striking clusters of functionally related
      targets among the top predictions for specific miRNAs. These include Notch target
      genes for miR-7, proapoptotic genes for the miR-2 family, and enzymes from a
      metabolic pathway for miR-277. We experimentally verified three predicted targets
      each for miR-7 and the miR-2 family, doubling the number of validated targets for
      animal miRNAs. Statistical analysis indicates that the best single predicted
      target sites are at the border of significance; thus, target predictions should
      be considered as tentative until experimentally validated. We identify features
      shared by all validated targets that can be used to evaluate target predictions
      for animal miRNAs. Our initial evaluation and experimental validation of target
      predictions suggest functions for two miRNAs. For others, the screen suggests
      plausible functions, such as a role for miR-277 as a metabolic switch controlling
      amino acid catabolism. Cross-genome comparison proved essential, as it allows
      reduction of the sequence search space. Improvements in genome annotation and
      increased availability of cDNA sequences from other genomes will allow more
      sensitive screens. An increase in the number of confirmed targets is expected to
      reveal general structural features that can be used to improve their detection.
      While the screen is likely to miss some targets, our study shows that valid
      targets can be identified from sequence alone.

PMID- 14691537
TI  - Detection and characterization of cellular immune responses using peptide-MHC
      microarrays.
AB  - The detection and characterization of antigen-specific T cell populations is
      critical for understanding the development and physiology of the immune system
      and its responses in health and disease. We have developed and tested a method
      that uses arrays of peptide-MHC complexes for the rapid identification,
      isolation, activation, and characterization of multiple antigen-specific
      populations of T cells. CD4(+) or CD8(+) lymphocytes can be captured in
      accordance with their ligand specificity using an array of peptide-MHC complexes
      printed on a film-coated glass surface. We have characterized the specificity and
      sensitivity of a peptide-MHC array using labeled lymphocytes from T cell receptor
      transgenic mice. In addition, we were able to use the array to detect a rare
      population of antigen-specific T cells following vaccination of a normal mouse.
      This approach should be useful for epitope discovery, as well as for
      characterization and analysis of multiple epitope-specific T cell populations
      during immune responses associated with viral and bacterial infection, cancer,
      autoimmunity, and vaccination.

PMID- 14691538
TI  - The virus that changed my world.

PMID- 14691539
TI  - Distinct mechanisms determine transposon inheritance and methylation via small
      interfering RNA and histone modification.
AB  - Heritable, but reversible, changes in transposable element activity were first
      observed in maize by Barbara McClintock in the 1950s. More recently, transposon
      silencing has been associated with DNA methylation, histone H3 lysine-9
      methylation (H3mK9), and RNA interference (RNAi). Using a genetic approach, we
      have investigated the role of these modifications in the epigenetic regulation
      and inheritance of six Arabidopsis transposons. Silencing of most of the
      transposons is relieved in DNA methyltransferase (met1), chromatin remodeling
      ATPase (ddm1), and histone modification (sil1) mutants. In contrast, only a small
      subset of the transposons require the H3mK9 methyltransferase KRYPTONITE, the
      RNAi gene ARGONAUTE1, and the CXG methyltransferase CHROMOMETHYLASE3. In crosses
      to wild-type plants, epigenetic inheritance of active transposons varied from
      mutant to mutant, indicating these genes differ in their ability to silence
      transposons. According to their pattern of transposon regulation, the mutants can
      be divided into two groups, which suggests that there are distinct, but
      interacting, complexes or pathways involved in transposon silencing. Furthermore,
      different transposons tend to be susceptible to different forms of epigenetic
      regulation.

PMID- 14691543
TI  - Research advocacy: why every scientist should participate.

PMID- 14691540
TI  - GAD2 on chromosome 10p12 is a candidate gene for human obesity.
AB  - The gene GAD2 encoding the glutamic acid decarboxylase enzyme (GAD65) is a
      positional candidate gene for obesity on Chromosome 10p11-12, a susceptibility
      locus for morbid obesity in four independent ethnic populations. GAD65 catalyzes
      the formation of gamma-aminobutyric acid (GABA), which interacts with
      neuropeptide Y in the paraventricular nucleus to contribute to stimulate food
      intake. A case-control study (575 morbidly obese and 646 control subjects)
      analyzing GAD2 variants identified both a protective haplotype, including the
      most frequent alleles of single nucleotide polymorphisms (SNPs) +61450 C>A and
      +83897 T>A (OR = 0.81, 95% CI [0.681-0.972], p = 0.0049) and an at-risk SNP (-243
      A>G) for morbid obesity (OR = 1.3, 95% CI [1.053-1.585], p = 0.014). Furthermore,
      familial-based analyses confirmed the association with the obesity of SNP +61450
      C>A and +83897 T>A haplotype (chi(2) = 7.637, p = 0.02). In the murine insulinoma
      cell line betaTC3, the G at-risk allele of SNP -243 A>G increased six times GAD2
      promoter activity (p < 0.0001) and induced a 6-fold higher affinity for nuclear
      extracts. The -243 A>G SNP was associated with higher hunger scores (p = 0.007)
      and disinhibition scores (p = 0.028), as assessed by the Stunkard Three-Factor
      Eating Questionnaire. As GAD2 is highly expressed in pancreatic beta cells, we
      analyzed GAD65 antibody level as a marker of beta-cell activity and of insulin
      secretion. In the control group, -243 A>G, +61450 C>A, and +83897 T>A SNPs were
      associated with lower GAD65 autoantibody levels (p values of 0.003, 0.047, and
      0.006, respectively). SNP +83897 T>A was associated with lower fasting insulin
      and insulin secretion, as assessed by the HOMA-B% homeostasis model of beta-cell
      function (p = 0.009 and 0.01, respectively). These data support the hypothesis of
      the orexigenic effect of GABA in humans and of a contribution of genes involved
      in GABA metabolism in the modulation of food intake and in the development of
      morbid obesity.

PMID- 14691541
TI  - Linkage of osteoporosis to chromosome 20p12 and association to BMP2.
AB  - Osteoporotic fractures are a major cause of morbidity and mortality in ageing
      populations. Osteoporosis, defined as low bone mineral density (BMD) and
      associated fractures, have significant genetic components that are largely
      unknown. Linkage analysis in a large number of extended osteoporosis families in
      Iceland, using a phenotype that combines osteoporotic fractures and BMD
      measurements, showed linkage to Chromosome 20p12.3 (multipoint allele-sharing
      LOD, 5.10; p value, 6.3 x 10(-7)), results that are statistically significant
      after adjusting for the number of phenotypes tested and the genome-wide search. A
      follow-up association analysis using closely spaced polymorphic markers was
      performed. Three variants in the bone morphogenetic protein 2 (BMP2) gene, a
      missense polymorphism and two anonymous single nucleotide polymorphism
      haplotypes, were determined to be associated with osteoporosis in the Icelandic
      patients. The association is seen with many definitions of an osteoporotic
      phenotype, including osteoporotic fractures as well as low BMD, both before and
      after menopause. A replication study with a Danish cohort of postmenopausal women
      was conducted to confirm the contribution of the three identified variants. In
      conclusion, we find that a region on the short arm of Chromosome 20 contains a
      gene or genes that appear to be a major risk factor for osteoporosis and
      osteoporotic fractures, and our evidence supports the view that BMP2 is at least
      one of these genes.

PMID- 14691544
TI  - Architecture and selectivity in aquaporins: 2.5 a X-ray structure of aquaporin Z.
AB  - Aquaporins are a family of water and small molecule channels found in organisms
      ranging from bacteria to animals. One of these channels, the E. coli protein
      aquaporin Z (AqpZ), has been shown to selectively conduct only water at high
      rates. We have expressed, purified, crystallized, and solved the X-ray structure
      of AqpZ. The 2.5 A resolution structure of AqpZ suggests aquaporin selectivity
      results both from a steric mechanism due to pore size and from specific amino
      acid substitutions that regulate the preference for a hydrophobic or hydrophilic
      substrate. This structure provides direct evidence on the molecular mechanisms of
      specificity between water and glycerol in this family of channels from a single
      species. It is to our knowledge the first atomic resolution structure of a
      recombinant aquaporin and so provides a platform for combined genetic,
      mutational, functional, and structural determinations of the mechanisms of
      aquaporins and, more generally, the assembly of multimeric membrane proteins.

PMID- 14691548
TI  - Economy of the mind.

PMID- 14691549
TI  - Antigen-specific T cells: analyses of the needles in the haystack.

PMID- 14691550
TI  - How mammals acquire and distribute iron needed for oxygen-based metabolism.

PMID- 14691553
TI  - Human epigenome project--up and running.

PMID- 14691551
TI  - Tre1, a G protein-coupled receptor, directs transepithelial migration of
      Drosophila germ cells.
AB  - In most organisms, germ cells are formed distant from the somatic part of the
      gonad and thus have to migrate along and through a variety of tissues to reach
      the gonad. Transepithelial migration through the posterior midgut (PMG) is the
      first active step during Drosophila germ cell migration. Here we report the
      identification of a novel G protein-coupled receptor (GPCR), Tre1, that is
      essential for this migration step. Maternal tre1 RNA is localized to germ cells,
      and tre1 is required cell autonomously in germ cells. In tre1 mutant embryos,
      most germ cells do not exit the PMG. The few germ cells that do leave the midgut
      early migrate normally to the gonad, suggesting that this gene is specifically
      required for transepithelial migration and that mutant germ cells are still able
      to recognize other guidance cues. Additionally, inhibiting small Rho GTPases in
      germ cells affects transepithelial migration, suggesting that Tre1 signals
      through Rho1. We propose that Tre1 acts in a manner similar to chemokine
      receptors required during transepithelial migration of leukocytes, implying an
      evolutionarily conserved mechanism of transepithelial migration. Recently, the
      chemokine receptor CXCR4 was shown to direct migration in vertebrate germ cells.
      Thus, germ cells may more generally use GPCR signaling to navigate the embryo
      toward their target.

PMID- 14691545
TI  - Transcriptome analysis of mouse stem cells and early embryos.
AB  - Understanding and harnessing cellular potency are fundamental in biology and are
      also critical to the future therapeutic use of stem cells. Transcriptome analysis
      of these pluripotent cells is a first step towards such goals. Starting with
      sources that include oocytes, blastocysts, and embryonic and adult stem cells, we
      obtained 249,200 high-quality EST sequences and clustered them with public
      sequences to produce an index of approximately 30,000 total mouse genes that
      includes 977 previously unidentified genes. Analysis of gene expression levels by
      EST frequency identifies genes that characterize preimplantation embryos,
      embryonic stem cells, and adult stem cells, thus providing potential markers as
      well as clues to the functional features of these cells. Principal component
      analysis identified a set of 88 genes whose average expression levels decrease
      from oocytes to blastocysts, stem cells, postimplantation embryos, and finally to
      newborn tissues. This can be a first step towards a possible definition of a
      molecular scale of cellular potency. The sequences and cDNA clones recovered in
      this work provide a comprehensive resource for genes functioning in early mouse
      embryos and stem cells. The nonrestricted community access to the resource can
      accelerate a wide range of research, particularly in reproductive and
      regenerative medicine.

PMID- 14691557
TI  - How are the sizes of cells, organs, and bodies controlled?

PMID- 14691560
TI  - A changing landscape.

PMID- 14691554
TI  - Inhibition of HIF2alpha is sufficient to suppress pVHL-defective tumor growth.
AB  - Biallelic inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) is
      linked to the development of hereditary (VHL-associated) and sporadic clear-cell
      renal carcinomas as well as other abnormalities. The VHL gene product, pVHL, is
      part of an E3 ubiquitin ligase complex that targets the alpha subunits of the
      heterodimeric transcription factor HIF (hypoxia-inducible factor) for degradation
      in the presence of oxygen. Here we report that a HIF2alpha variant lacking both
      of its two prolyl hydroxylation/pVHL-binding sites prevents tumor inhibition by
      pVHL in a DNA-binding dependent manner. Conversely, downregulation of HIF2alpha
      with short hairpin RNAs is sufficient to suppress tumor formation by pVHL
      defective renal carcinoma cells. These results establish that tumor suppression
      by pVHL is linked to regulation of HIF target genes.

PMID- 14691562
TI  - The physiologic basis of assembly and activation of the plasma kallikrein/kinin
      system.

PMID- 14691563
TI  - Autologous platelets as a source of proteins for healing and tissue regeneration.
AB  - Platelets are known for their role in haemostasis where they help prevent blood
      loss at sites of vascular injury. To do this, they adhere, aggregate and form a
      procoagulant surface leading to thrombin generation and fibrin formation.
      Platelets also release substances that promote tissue repair and influence the
      reactivity of vascular and other blood cells in angiogenesis and inflammation.
      They contain storage pools of growth factors including PDGF, TGF-beta?and VEGF as
      well as cytokines including proteins such as PF4 and CD40L. Chemokines and newly
      synthesised active metabolites are also released. The fact that platelets secrete
      growth factors and active metabolites means that their applied use can have a
      positive influence in clinical situations requiring rapid healing and tissue
      regeneration. Their administration in fibrin clot or fibrin glue provides an
      adhesive support that can confine secretion to a chosen site. Additionally,the
      presentation of growth factors attached to platelets and/or fibrin may result in
      enhanced activity over recombinant proteins. Dental implant surgery with guided
      bone regeneration is one situation where an autologous platelet-rich clot clearly
      accelerates ossification after tooth extraction and/or around titanium implants.
      The end result is both marked reductions in the time required for implant
      stabilisation and an improved success rate. Orthopaedic surgery, muscle and/or
      tendon repair, reversal of skin ulcers, hole repair in eye surgery and cosmetic
      surgery are other situations where autologous plate-lets accelerate healing. Our
      aim is to review these advances and discuss the ways in which platelets may
      provide such unexpected beneficial therapeutic effects.

PMID- 14691564
TI  - The factor V C1 domain is involved in membrane binding: identification of
      functionally important amino acid residues within the C1 domain of factor V using
      alanine scanning mutagenesis.
AB  - The contribution of the factor Va C1 domain (fVa-C1) to assembly of the
      prothrombinase complex has not been previously investigated. The homologous fVa
      C2 domain contains a binding site for phosphatidylserine (PS) that includes the
      indole moieties of Trp(2063)/Trp(2064) at the apex of spike-1. In order to
      investigate the structure and function of fVa-C1 a molecular model was
      constructed based on the structure of fVa-C2. The aromatic and hydrophobic side
      chains of Tyr (1956) /Leu (1957) in fVa-C1 are located at the predicted apex of
      spike-3. Exposed charged and hydrophobic residues in fVa-C1 were changed to
      alanine in clusters of 1-3 mutations per construct. The resultant 20 mutants were
      expressed in COS cells and screened for binding to immobilized PS and
      prothrombinase activity on phospholipid vesicles containing either 25% or 5% PS.
      Two mutants, (Y1956,L1957)A, and (R2023,R2027)A showed both decreased binding to
      immobilized PS and a selective decrease in prothrombinase activity on membranes
      containing 5% PS. The interaction of purified (Y1956,L1957)A with phospholipid
      vesicles was studied using fluorescence resonance energy transfer and
      prothrombinase assays. The affinity of (Y1956,L1957)A binding to 25% PS membranes
      was reduced 12-fold compared to rHFVa. Prothrombin activation in the presence of
      (Y1956,L1957)A was markedly impaired on phos-pholipid vesicles containing 10% or
      less PS. We conclude that solvent exposed hydrophobic and aromatic amino acids in
      both fVa-C1 and fVa-C2 contribute to the interaction of factor V with PS
      membranes.

PMID- 14691565
TI  - A novel gene mutation in the 60s loop of human coagulation factor VII -
      inhibition of interdomain crosstalk.
AB  - A novel mutation in the factor VII gene resulting in procoagulant activity of
      7.5% and antigen levels of 23% is presented. Single-stranded conformational
      polymorphism and DNA sequencing analysis revealed heterozygous shifts, and
      mutations were detected in exons 5, 7 and 8. The mutant L204P in exon 7 was
      novel, while the common polymorphisms, H115H and R353Q, were located in exons 5
      and 8, respectively. The molecular effect of the L204P mutation was characterized
      using recombinant mammalian expression in Chinese hamster ovary cells. Low levels
      (4 ng/ml) of secreted mutant protein were found in transiently transfected cells
      compared to wild-type factor VII (83 ng/ml). Metabolic labeling demonstrated that
      the rate of mutant protein synthesis was similar to that of wild-type FVII, and
      the mutant protein accumulated intracellularly with no signs of increased
      degradation during a four-hour chase. No interaction between secreted P204
      protein and immobilized soluble tissue factor was detected using surface plasmon
      reso-nance. The activation rate of recombinant mutant FVII protein was strongly
      reduced compared to wild-type FVII. A 9-fold reduction in the rate of FX
      activation was detected whereas Km was nearly the same for wild-type and the
      mutant. This slow rate was caused by a correspondingly lowered rate of P204
      activation. A synthetic peptide sequence comprising amino acids 177-206 blocked
      binding of FVIIa to the TF-chip, and the subsequent factor X activation with an
      IC(50) value of 0.5 micro M in a chromogenic factor Xa assay. Additionally,
      evaluation of the peptide by surface plasmon resonance analysis resulted in
      inhibition of complex formation with an apparent K(I) of 7 micro M.

PMID- 14691566
TI  - Sequence of the rat factor VIII cDNA.
AB  - Factor VIII acts as an essential compound of the tenase complex of the
      coagulation system. Herein we report the cDNA of the rat factor VIII. The rat
      cDNA comprises 6777 nucleotides and encodes a protein of 2258 amino acids, 61
      amino acids less than mouse and 92 amino acids less than human factor VIII. The
      over-all identity compared to human cDNA is 61% on the cDNA and 51% on the amino
      acid level. In cDNA, highest levels of sequence identity can be observed in the A
      and C domains (ranging between 68% and 73%), whereas B domain and the small
      acidic regions are more divergent (34% - 49%). Compared to mouse and human most
      sites for posttranslational modifications such as sulfatation and glycosylation
      as well as thrombin and protein C cleavage sites are conserved in rat.
      Alternative transcripts lacking exon 17 and/or comprising additional 26 bp due to
      alternative splicing of exon 20 were found. Furthermore, 13 polymorphisms (seven
      in exon 14, one in exon 20, 23, 24, and 25, two in the 3' UTR) three of which
      lead to an amino acid exchange could be detected. Our findings might provide new
      insights into the structure-function analysis of the factor VIII protein and
      might prove useful for future animal models addressing the function of factor
      VIII.

PMID- 14691567
TI  - Fibrinogen C-terminal peptidic sequences (Haptides) modulate fibrin
      polymerization.
AB  - We previously described synthetic peptides of 19-21 amino acid residues,
      homologous to the C-termini of fibrinogen Fib(340) and Fib(420), from the beta
      chain (Cbeta), the extended alphaE chain (CalphaE) and near the end of the gamma
      chain (preCgamma) which elicited attachment (haptotactic) responses from
      mesenchymal cells. We named these haptotactic peptides -Haptides. The effects of
      Haptides on fibrin clot formation was evaluated and their possible effects on
      platelet aggregation was examined. The Haptides Cbeta,CalphaE and preCgamma, (2
      10 micro M) increased fibrin clot turbidity and also decreased thrombin-induced
      clotting time. Higher concentrations (>120 micro M of Cbeta or preCgamma) induced
      fibrinogen precipitation even without thrombin. These precipi-tates exhibited
      different ultrastructure from thrombin-induced fibrin by scanning and
      transmission microscopy. C-terminal peptides of the other fibrinogen chains
      exerted no such effects. Sepharose beads covalently coated with either whole
      fibrinogen or Haptides (SB-Fib or SB-Haptide) highly adsorbed free (FITC)
      Haptides. In aqueous solution, Haptides formed nano-par-ticles with average size
      of approximately 150 nm in diameter. We suggest that such positively charged
      aggregates could serve to nucleate and accelerate fibrin gel formation. These
      results also indicate that Cbeta and preCgamma sequences within fibrin(ogen)
      participate in the docking and condensation of fibrin(ogen) during its assembly
      into a fibrin clot. By contrast, Haptides up to 100 micro M did not bind to
      platelets, and had no effect on platelet aggregation. Our findings highlight the
      roles of the C-terminal sequences of the beta and gamma chains in fibrin(ogen)
      polymerization as well as in cell attachment.

PMID- 14691568
TI  - Clot penetration and fibrin binding of amediplase,a chimeric plasminogen
      activator (K2 tu-PA).
AB  - Amediplase (K(2) tu-PA) is a hybrid plasminogen activator, consisting of the
      kringle 2 domain of alteplase and the protease domain of urokinase. The objective
      of this study was to determine the in vitro clot penetration of amediplase in
      relation to its fibrin binding and to compare the properties with those of
      alteplase. The clot lysis activity of amediplase in internal clot lysis models
      (both purified system and plasma system) was about 10 times less than that of
      alteplase. The clot lysis activity of amediplase in an external clot lysis model
      (plasma system) was similar to that of alteplase at therapeutic concentrations
      around 1 micro g/ml. The fibrin-clot binding properties of amediplase and
      alteplase were studied in a purified system as well as in a plasma system. In
      both systems amediplase bound to fibrin although to a significantly lower extent
      than alteplase. The binding of amediplase or alteplase did not increase during
      plasmin-mediated degradation of fibrin. The binding of amediplase was fully
      inhibited by epsilon-aminocaproic acid, indicating that the observed binding was
      specific and occurred via the lysine binding site in the kringle of amediplase.
      Clot penetration was studied during pressure-driven fluid permeation using
      syringes containing plasma clots. Amediplase was able to enter the clot without
      significant hindrance, while alteplase was concentrated on the top of the plasma
      clot and hardly entered into the inner parts of the clot. Diffusion-driven clot
      penetration was studied during clot lysis using confocal microscopy. Alteplase
      was detected on or close to the clot surface, while two-chain urokinase, which
      has no affinity to fibrin, was also detected deep inside the clot. Amediplase
      showed a penetration behaviour, which was distinct from that of alteplase and
      similar to that of two-chain urokinase. We concluded that the fibrin binding of
      amediplase is moderate and does not hinder clot penetration under permeation
      driven or diffusion-driven transport conditions. Enhanced clot penetration,
      especially in large clots, could allow a more efficient lysis during thrombolytic
      therapy.

PMID- 14691569
TI  - Interaction of high molecular weight kininogen binding proteins on endothelial
      cells.
AB  - Cell surface proteins reported to participate in the binding and activation of
      the plasma kinin-forming cascade includes gC1qR, cytokeratin 1 and u-PAR. Each of
      these proteins binds high molecular weight kininogen (HK) as well as Factor XII.
      The studies on the interaction of these proteins, using dot-blot analysis,
      revealed that cytokeratin 1 binds to both gC1qR and u-PAR while gC1qR and u-PAR
      do not bind to each other. The binding properties of these proteins were further
      analyzed by gel filtration. When biotinylated cytokeratin 1 was incubated with
      either gC1qR or u-PAR and gel filtered, a new, higher molecular weight peak
      containing biotin was observed indicating complex formation. The protein shift
      was also similar to the biotin shift. Further, immunoprecipitation of solubilized
      endo-thelial cell plasma membrane proteins with anti-gC1qR recovered both gC1qR
      and cytokeratin 1, but not u-PAR. Immunoprecipitation with anti-u-PAR recovered
      only u-PAR and cytokeratin 1. By competitive ELISA, gC1qR inhibits u-PAR from
      binding to cytokeratin 1; u-PAR inhibits gC1qR binding to a lesser extent and
      requires a 10-fold molar excess. Our data suggest that formation of HK (and
      Factor XII) binding sites along endothelial cell membranes consists of
      bimolecular com-plexes of gC1qR-cytokeratin 1 and u-PAR-cytokeratin 1, with gC1qR
      binding being favored.

PMID- 14691571
TI  - The angiotensin-converting-enzyme insertion/deletion polymorphism is not related
      to venous thrombosis.
AB  - The insertion/deletion (I/D) polymorphism of the gene for angiotensin-converting
      enzyme (ACE) is associated with ACE plasma levels and activity. Conflicting
      results have been reported about the relevance of this polymorphism for venous
      thrombosis. The aim of the present study was to analyze the role of this
      polymorphism for deep venous thrombosis. The study was designed as a case-control
      study, including 330 patients with documented deep venous thrombosis and 354
      controls. ACE genotype was determined by size-analysis of polymerase chain
      reaction products. Results showed that, ACE genotype frequencies were similar
      between patients (II: 24.8%; ID: 43.3%; DD: 31.8%) and controls (II: 22.9%; ID:
      50.6%; DD: 26.6%, P = 0.15). The adjusted odds ratio of carriers of the DD geno
      type for venous thrombosis was 1.24 (95% confidence interval 0.90-1.80). The
      polymorphism was furthermore not associated with age at first thromboembolic
      event or the occurrence of pulmonary embolism. From these results, we can
      conclude that the ACE I/D polymorphism is not a significant risk factor for deep
      venous thrombosis.

PMID- 14691570
TI  - Antithrombotic role of nitric oxide in rats under physiological conditions.
AB  - Although sepsis-induced release of nitric oxide (NO) is known to have an
      antithrombotic effect, it is unknown if NO exerts this same effect under
      physiological conditions. We have there-fore attempted to determine whether or
      not NO protects against thrombus formation in normal Wistar rats injected with
      various amounts (0.8, 4.0, 20.0 and 100 mg/kg/4 hr) of L-NAME (N (omega)-nitro-l
      arginine methyl ester), an NO synthase inhibitor, via the tail vein. Plasma
      levels of D-dimer fragments of fibrin were significantly increased in rats
      receiving L-NAME (0.21+/-0.04, 0.22+/-0.05, 0.26+/-0.07, 0.59+/-0.17 micro g/mL,
      means+/-SE; p<0.05, 0.05, 0.05, 0.01: L-NAME 0.8, 4, 20, 100, respectively,
      compared with control levels: <0.06 micro g/mL), and thrombin-anti-thrombin
      complex (TAT) levels were significantly increased in rats receiving 20mg/kg/4 hr
      or greater doses of L-NAME (4.5+/-1.1, 4.7+/-1.4, 18.7+/-4.9, 42.5+/-4.0 ng/mL,
      NS, NS, p<0.05, 0.01, respectively, compared with control levels: 3.8+/-1.2
      ng/mL). Glomerular fibrin deposition was increased in a dose-dependent manner in
      rats receiving L-NAME (6.8+/-1.5, 13.9+/-1.6, 32.4+/-2.6, 49.2+/-5.2%, p<0.05,
      0.05, 0.01, 0.01, respectively, com-pared with control levels: 0.0+/-0.0%). Renal
      dysfunction and hepatic dysfunction were observed in rats receiving 20mg/kg/4 hr
      or greater, or 100mg/kg/4 hr, doses of L-NAME, respectively. Mean blood pressure
      was also elevated in rats receiving L-NAME in a dose-dependent manner. These
      findings suggest that NO, in addition to regulating blood pressure, is involved
      in prevention of thrombus formation under physiological circumstances.

PMID- 14691572
TI  - Decreased anticoagulant response to tissue factor pathway inhibitor in patients
      with venous thromboembolism and otherwise no evidence of hereditary or acquired
      thrombophilia.
AB  - No relevant deficiency of TFPI or genetic polymorphisms could thus far
      consistently be associated with venous thromboembolism. We hypothesized that the
      substrates of the TFPI protein, including FVII or FX (rather than the protein
      itself) could induce a hypercoagulable state. We created a novel TF-based
      clotting assay that evaluated the anticoagulant response to exogenously added
      recombinant TFPI. The response to TFPI was expressed as the ratio of the clotting
      time with and with-out TFPI. By using 118 healthy controls, we established a
      reference range between 1.31 and 1.93 (mean value +/-2 standard deviations (SD),
      1.62 +/-0.31). We then evaluated samples from 120 patients with a history of
      venous thromboembolism but no evidence of hereditary and acquired thrombophilia.
      The range Coagulation Laboratory, Division of Haematology, University Hospital of
      Zurich, Zurich, Switzerland of the patients' ratios was significantly (P < 0.001)
      lower, falling between 1.2 and 1.78 (mean value +/-2 SD, 1.49 +/-0.29). Of the
      120 patients, 39 (32.5%) had a TFPI sensitivity ratio below the 10th percentile
      of the controls, compared with 11 (9.3%) of the healthy controls. The crude odds
      ratio for venous thrombosis for subjects with a TFPI sensitivity ratio below the
      10th percentile was 13 (95% CI; range, 3.1 to 54.9) compared with those with a
      ratio above 1.8 (90th percentile). Patients with idiopathic thromboembolism did
      not have a decreased TFPI sensitivity ratio more often than patients with
      thrombosis with a circumstantial risk factor. Based on these results, a reduced
      response to TFPI may lead to an increased risk of venous thrombosis.

PMID- 14691573
TI  - Use of pharmacogenetics and clinical factors to predict the maintenance dose of
      warfarin.
AB  - Knowledge of pharmacogenetics may help clinicians predict their patients'
      therapeutic dose of warfarin, thereby decreasing the risk of bleeding during
      warfarin initiation. Our goal was to use pharmacogenetics to develop an algorithm
      that uses genetic, clinical, and demographic factors to estimate the warfarin
      dose a priori. We collected a blood sample, demographic variables, laboratory
      values, smoking status, names of medications, and dietary history from 369
      patients who were taking a maintenance dose of warfarin. Using polymerase chain
      reaction, we genotyped each participant for the presence of 8 polymorphisms in
      the cytochrome P450 2C9 system. Using multiple regression, we quantified the
      association between warfarin dose and all factors. Advanced age, lower body
      surface area (BSA), and the presence of cytochrome P450 2C9 *2 or *3 single
      nucleotide polymorphisms were strongly associated (P < 0.001) with lower warfarin
      dose: the maintenance dose decreased by 8% per decade of age, by 13% per standard
      deviation decrease in BSA, by 19% per 2C9*2 allele, and by 30% per 2C9*3 allele.
      Warfarin doses were 29% lower in patients who took amiodarone, 12% lower in
      patients who took simvastatin, 21% lower in patients whose target INR was 2.5
      rather than 3.0, and 11% lower in white rather than African-American participants
      (P < 0.05 for these comparisons). An algorithm that included these factors and
      one of borderline significance (sex), explained 39% of the variance in the
      maintenance warfarin dose. Use of this pharmacogenetic model had potential to
      prevent patients from being overdosed when initiating warfarin: we estimate that
      only 24 (6.5%) patients would have been over- dosed by >2 mg/day with
      pharmacogenetic dosing compared to 59 (16%) patients who would have been
      overdosed if they had been prescribed the empirical dose of 5 mg/day (P < 0.001).
      In conclusion, the maintenance warfarin dose can be estimated from demographic,
      clinical, and pharmacogenetic factors that can be obtained at the time of
      warfarin initiation.

PMID- 14691574
TI  - Potential interaction between acenocoumarol and diclofenac, naproxen and
      ibuprofen and role of CYP2C9 genotype.
AB  - NSAIDs are reported to increase the risk of bleeding in coumarin users. The
      mechanism underlying this risk is inhibition of platelet aggregation, however a
      pharmacokinetic mechanism resulting in an increased International Normalised
      Ratio (INR) was proposed in some case reports in warfarin treated patients. In
      this retrospective cohort study the influence of diclofenac, naproxen and
      ibuprofen on the INR of outpatients stabilised on acenocoumarol therapy was
      investigated. We also determined the role of cytochrome P450 2C9 (CYP2C9)
      polymorphism on coumarin dosage and INR in NSAID users. The study was carried out
      at the Groningen Outpatient Thrombosis Service. A retrospective cohort study
      among patients who received both acenocoumarol and one of the NSAIDs under study
      was performed. Patients whose INR rose above the upper level of the therapeutic
      range (INR above 3.5 or 4.0) after an NSAID under study was added to the
      acenocoumarol therapy, were compared with patients who did not show such an
      elevation. A two-sample t-test (average acenocoumarol dosage, age), and chi
      square tests (sex, therapeutic range, type of NSAID) were used to test for
      differences. Genotyping was carried out by analysing blood samples for the
      relevant CYP2C9 alleles. The study population consisted of 112 patients on stable
      acenocoumarol therapy, of which 52 (46%) showed an elevation of the INR above the
      desired therapeutic level (INR 3.5 and 4.0 respectively) after the start of an
      NSAID under study. In 12 patients, the INR increased above 6. The INR of the
      other 60 patients (54%) remained constant after the start of one of the NSAIDs
      under study. There were no statistically significant differences between patients
      with increased INR and patients without increased INR with regard to age, sex,
      therapeutic range and average acenocoumarol dosage. Eighty patients, of whom 36
      showed an increased INR as a result of a potential acenocoumarol-NSAID drug
      interaction, were included in the genotyping study. No association between CYP2C9
      genotype and an increased INR as a result of the drug-drug interaction was found.
      In nearly half of a cohort of elderly patients, the INR increased beyond the
      therapeutic range (INR 3.5 or 4.0) as a result of a potential pharmacokinetic
      drug-drug interaction between acenocoumarol and diclofenac, naproxen and
      ibuprofen. The average increase in INR was between 1 and 4. Polymorphism of
      CYP2C9 does not seem to be a relevant risk factor for the NSAID-acenocoumarol
      interaction.

PMID- 14691575
TI  - A role for p38 MAP kinase in platelet activation by von Willebrand factor.
AB  - Platelet activation induced by von Willebrand factor (VWF) binding to the
      membrane GPIb-IX-V receptor involves multiple signal transduction pathways. Among
      these, recruitment and activation of the FCgammaRIIA and stimulation of
      phospholipase A2 represent independent events equally essential to support a
      complete platelet response. Phospholipase A2 is activated by calcium and by
      phosphorylation through MAP kinases. In this work, we found that VWF stimulated
      the rapid and sustained phosphorylation of p38 MAP kinase (p38MAPK). In vitro
      kinase assay revealed that VWF-stimulated phosphorylation of p38MAPK was
      associated with increased kinase activity. Binding of VWF to GPIb-IX-V, but not
      to integrin alphaIibbeta3, was required to support phosphorylation of p38MAPK.
      Neither the blockade of the membrane FCgammaRIIA by a specific monoclonal
      antibody or the prevention of thromboxane A(2) synthesis by cyclooxygenase
      inhibitors affected VWF-induced p38MAPK activation. How-ever, phosphorylation of
      p38MAPK was prevented by the tyro-sine kinase Syk inhibitor piceatannol.
      Treatment of platelets with the p38MAPK inhibitor SB203580 totally prevented VWF
      stimulated platelet aggregation. Moreover, release of arachidonic acid induced by
      VWF was strongly impaired by inhibition of p38MAPK. We also found that VWF
      induced phosphorylation of cytosolic phospholipase A(2), and that this process
      was prevented by the p38MAPK inhibitor SB203580. These results demon-strate that
      p38MAPK is a key element in the FCgammaRIIA-independent pathway for VWF-induced
      platelet activation, and is involved in the stimulation of phospholipase A(2) and
      arachidonic acid release.

PMID- 14691576
TI  - Critical residues for ligand binding in blade 2 of the propeller domain of the
      integrin alphaIIb subunit.
AB  - Ligand binding to integrin alphaIIbbeta3 is a key event of thrombus formation.
      The propeller domain of the alphaIIb subunit has been implicated in ligand
      binding. Recently, the ligand binding site of the alphaV propeller was determined
      by crystal structure analysis. However, the structural basis of ligand
      recognition by the alphaIIb propeller remains to be determined. In this study, we
      conducted site-directed mutagenesis of all residues located in the loops
      extending above blades 2 and 4 of the alphaIIb propeller, which are spatially
      close to, but distinct from, the loops that contain the binding site for an RGD
      ligand in the crystal structure of the alphaV propeller. Replacement by alanine
      of Q111, H112 or N114 in the loop within the blade 2 (the W2:2-3 loop in the
      propeller model) abolished binding of a ligand-mimetic antibody and fibrinogen to
      alphaIIbbeta3 induced by different types of integrin activation including
      activation of alphaIIbbeta3 by beta3 cytoplasmic mutation. CHO cells stably
      expressing recombinant alphaIibbeta3 bearing Q111A, H112A or N114A mutation did
      not exhibit alphaIibbeta3-mediated adhesion to fibrinogen. According to the
      crystal structure of alphaVbeta3, the alphaV residue corresponding to
      alphaIIbN114 is exposed on the integrin surface and close to the RGD binding
      site. These results suggest that the Q111, H112 and N114 residues in the loop
      within blade 2 of the alphaIIb propeller are critical for ligand binding,
      possibly because of direct interaction with ligands or modulation of the RGD
      binding pocket.

PMID- 14691577
TI  - The influence of selective serotonin reuptake inhibitors on human platelet
      serotonin.
AB  - Clinical depression has been proposed to be an independent risk factor for
      cardiovascular disease. While it is suggested that selective serotonin reuptake
      inhibitors (SSRIs) reduce the risk of acute cardiovascular problems of depressed
      patients, the effect of SSRIs on platelets, the only blood cells committed to
      serotonin (5-HT) transport, remains largely unknown. The goal of this pilot study
      was to measure the 5-HT levels in platelets of untreated and SSRI-treated
      depressed patients and normal subjects and to determine whether the interaction
      of SSRIs with platelets can explain their possible cardiovascular benefit in
      patients with depression. Platelet 5-HT was determined by an immunocytochemical
      assay and high-pressure liquid chromatography with electrochemical detection
      (HPLC-ECD). In normal control subjects without cardiovascular disease, 78 +/- 8%
      of platelets were 5-HT-positive (n = 14). Depression caused a significant
      reduction in platelet 5-HT to 46 +/- 21% in untreated patients (n = 13) and 22 +/
      13% in SSRI-treated patients (n = 14). As a class, all selective serotonin
      reuptake inhibitors significantly reduced the 5-HT concentration in patient
      platelets. An inverse relationship of 5-HT level and dose of medication might be
      suggested. These results correlated well with 5-HT data from HPLC (r = 0.8509, p
      < 0.001). SSRIs did not affect platelet aggregation and dense granule release in
      response to thrombin, but significantly reduced ADP-induced platelet aggregation
      and dense granule release in both patient and normal control samples. The active
      inhibition of platelet aggregation by SSRIs might explain their cardiovascular
      benefit.

PMID- 14691578
TI  - Effects of the R216Q mutation of GATA-1 on erythropoiesis and
      megakaryocytopoiesis.
AB  - The transcription factor GATA-1, together with its cofactor FOG-1, regulates
      erythropoiesis and megakaryocytopoiesis. Mutations in the DNA or FOG-1 binding
      sites of its N-terminal zinc finger result in different illnesses. Alterations of
      the FOG-1 face are responsible for dyserythropoietic anemia with thrombocytopenia
      while R216Q, the only mutation identified in the DNA face, induces X-linked
      thrombocytopenia with thalassemia (XLTT). The former disorder has been studied in
      detail whereas little is known about the latter since only one family has been
      investigated. We studied a second family with an R216Q, showing that XLTT and
      dyserythropoietic anemia with thrombocytopenia, even if different clinical
      entities, are closely related disorders. In both cases, patients present mild
      dyserythropoiesis, red cell hemolysis, severely defective maturation of
      megakaryocytes, macrothrombocytopenia with alpha-granule deficiency, and
      abnormalities of the cytoplasmic membrane system. However, a thalassemia minor
      phenotype has only been described in patients with XLTT whereas severe anemia and
      thrombocytopenia with evident defects of platelet composition and function may be
      observed only in dyserythropoietic anemia with thrombocytopenia.

PMID- 14691579
TI  - PlA polymorphism of the glycoprotein IIIa and efficacy of reperfusion therapy in
      patients with acute myocardial infarction.
AB  - The Pl(A) polymorphism of the platelet glycoprotein IIIa gene is associated with
      altered platelet function and response to antiplatelet drugs. We sought to assess
      whether the Pl(A) polymorphism influences myocardial salvage achieved by
      reperfusion therapy in patients with acute myocardial infarction. We analyzed 292
      patients enrolled in 2 randomized trials that compared stenting plus abciximab
      with thrombolysis (alteplase alone or alteplase plus abciximab) in acute
      myocardial infarction. Patients were genotyped for the Pl (A) polymorphism using
      polymerase chain reaction with fluorogenic probes. Technetium-99m sestamibi was
      injected before and 1-2 weeks after reperfusion treatment. The scintigrams
      enabled the calculation of the initial perfusion defect, final infarct size, and
      the proportion of initial defect salvaged by reperfusion (salvage index).
      Clinical follow-up was done up to 18 months after primary treatment. The genotype
      distribution was as follows: Pl (A2/A2) in 3.4%, Pl (A1/A2) in 24.7% and Pl
      (A1/A1) in 71.9% of patients. There were no significant differences between Pl(
      A2) allele carriers and Pl(A1/A1) patients in salvage index (0.4+/-0.50 vs. 0.4+/
      0.43, respectively, P=0.48), final infarct size (16.8+/-20.8% vs. 18.4+/-19.1% of
      left ventricle, respectively, P=0.46) as well as 18-month mortality (8.5%
      vs.7.1%, respectively, P=0.69). The lack of relationship between Pl(A2) allele
      and myocardial salvage was observed for both reperfusion strategies, stenting and
      thrombolysis. Thus, these findings show that the functional Pl(A) polymorphism of
      platelet glycoprotein IIIa has no influence on the degree of myocardial salvage
      achieved by reperfusion therapies in patients with acute myocardial infarction.

PMID- 14691580
TI  - Increased level of oxidized LDL-dependent monocyte-derived microparticles in
      acute coronary syndrome.
AB  - We measured and compared the levels of plasma soluble (s) P-selectin, sCD40L,
      platelet-derived microparticles (PDMP), monocyte-derived microparticles (MDMP),
      and anti-oxidized LDL antibody, to obtain a better understanding of their
      potential contribution to vascular complications in acute coronary syndrome
      (ACS). The concentrations of sP-selectin, sCD40L, PDMP, and MDMP in ACS patients
      were significantly higher than those in normal controls and patients with stable
      angina. When levels of these markers were compared with differences in
      concentration of anti-oxidized LDL antibody, all markers were significantly
      higher in ACS patients with a high level of anti-oxidized LDL antibody. Next, a
      monocytic cell line (THP-1) was incubated with high shear stress-induced platelet
      aggregates and PDMP. After incubation,THP-1 cells generated tissue factor
      expressing MDMPs. This finding was particularly significant in the presence of
      oxidized LDL. These findings suggest that elevated levels of MDMPs may be a sign
      of atherosclerotic development in ACS patients, particularly those who exhibit
      anti-oxidized LDL antibodies.

PMID- 14691581
TI  - A microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated
      with increased bilirubin and HDL levels but not with coronary artery disease.
AB  - Heme oxygenase 1 (HO-1) is involved in the generation of the endogenous anti
      oxidant bilirubin which exerts beneficial effects against arteriosclerosis. A
      (GT) repeat polymorphism in the HO-1 promoter region modulates HO-1 expression in
      response to oxidative stress. Recently, this polymorphism has been reported to
      protect from coronary artery disease in Orientals. We intended to confirm this
      observation in Caucasians. We studied 649 individuals with myocardial infarction
      (n=258), stable coronary artery disease (n=180) and controls without coronary
      artery disease (n=211). Carriers of short alleles (<25 repeats) had higher
      bilirubin levels (median 0.66 mg/dL, IQR 0.49 to 0.91) compared to non-carriers
      (median 0.61 mg/dL, IQR 0.45 to 0.82; p=0.03) and a more favourable lipid profile
      (HDL median 47 mg/dL, IQR 40 to 50 vs. median 45, IQR 37 to 55, p=0.01;
      triglycerides median 118 mg/dL, IQR 87 to 174 vs. median 132, IQR 97 to 191,
      p=0.03). However, no significant differences of the genotype distribution were
      observed between the three groups in this Caucasian study population (p=0.94).
      Although potentially beneficial effects of the short HO-1 allele on lipid profile
      and serum bilirubin were observed, in contrast to Orientals, the HO-1 genotype
      was not associated with coronary artery disease in Caucasians.

PMID- 14691582
TI  - Antithrombin reduces the ischemia/reperfusion-induced spinal cord injury in rats
      by attenuating inflammatory responses.
AB  - Antithrombin (AT) reveals its antiinflammatory activity by promoting endothelial
      release of prostacyclin (PGI(2)) in vivo. Since neuroinflammation is critically
      involved in the development of ischemia/reperfusion (I/R)-induced spinal cord
      injury (SCI), it is possible that AT reduces the I/R-induced SCI by attenuating
      the inflammatory responses. We examined this possibility using rat model of I/R
      induced SCI in the present study. AT significantly reduced the mortality and
      motor disturbances by inhibiting reduction of the number of motor neurons in
      animals subjected to SCI. Microinfarctions of the spinal cord seen after
      reperfusion were markedly reduced by AT. AT significantly enhanced the I/R
      induced increases in spinal cord tissue levels of 6-keto-PGFIalpha, a stable
      metabolite of PGI2. AT significantly inhibited the I/R-induced increases in
      spinal cord tissue levels of TNF-alpha, rat interleukin-8 and myeloperoxidase. In
      contrast,Trp(49) -modified AT did not show any protective effects. Pretreatment
      with indomethacin significantly reversed the protective effects of AT. An
      inactive derivative of factor Xa, which selectively inhibits thrombin generation,
      has been shown to fail to reduce SCI. Taken together, these observations strongly
      suggested that AT might reduce I/R-induced SCI mainly by the antiinflammatory
      effect through promotion of endothelial production of PGI(2). These findings also
      suggested that AT might be a potential neuroprotective agent.

PMID- 14691583
TI  - E-Selectin and restenosis after femoropopliteal angioplasty: prognostic impact of
      the Ser128Arg genotype and plasma levels.
AB  - Perivascular inflammation plays a key role in the development of restenosis after
      percutaneous transluminal angioplasty (PTA). The adherence of leucocytes to the
      activated endothelium, an essential feature in the restenotic process, is
      mediated by the cellular adhesion molecule E-Selectin. A DNA polymorphism in the
      regulator region of E-Selectin at codon 561 (Ser128Arg) is suggested to modulate
      the molecule's physiological effects. Therefore, we investigated the association
      between the E-Selectin Ser128Arg genotype, E-Selectin plasma levels and
      restenosis after femoropopliteal PTA. We prospectively studied 175 consecutive
      patients with peripheral artery disease and intermittent claudication (n=126) or
      critical limb ischemia (n=49) who underwent primary successful femoropopliteal
      balloon angioplasty. E-Selectin Ser128Arg genotype and base-line E-Selectin
      plasma levels were determined and patients were followed up for median 12 months
      (IQR 11 to 14, total range 6 to 24) for the occurrence of postangioplasty
      restenosis(>/=50%). E-Selectin plasma levels in homozygous Arg128Arg and
      heterozygous Ser128Arg patients were significantly higher compared to wildtype
      Ser128Ser patients (p=0.041). Patency rates for wildtype Ser128Ser, heterozygous
      Ser128Arg and homozygous Ser128Ser patients were 57%, 44% and 50% at 6 months,
      and 46%, 40% and 17%, at 12 months, respectively (Log Rank p=0.31). Patency rates
      for increasing tertiles of E-Selectin were 61%, 58% and 37% at 6 months, and 54%,
      45% and 30% at 12 months, respectively (Log Rank p=0.020). Patients with an E
      Selectin plasma level above 44.9 mg/dL (third tertile) had an 1.9-fold increased
      adjusted risk for restenosis (95% CI 1.09 to 3.30). E-Selectin plasma levels are
      modulated by the E-Selectin Ser128Arg genotype, and predict the risk for
      restenosis after PTA in patients with PAD. A direct association of the Ser128Arg
      polymorphism with late postangioplasty failure could not be demonstrated.

PMID- 14691584
TI  - Expression analysis of the human kallikrein 7 (KLK7) in breast tumors: a new
      potential biomarker for prognosis of breast carcinoma.
AB  - Kallikreins are a subgroup of serine proteases that are involved in the post
      translational processing of polypeptide precursors. Growing evidence suggests
      that many kallikreins are implicated in carcinogenesis. Human kallikrein gene 7
      (KLK7; HSCCE) is a new member of the human kallikrein gene family. KLK7 is
      expressed in normal breast tissue and is up-regulated in breast cancer cells by
      estrogens and glucocorticoids. In the present study, expression of the KLK7 gene
      in 92 breast cancer tissues was analyzed by reverse transcription-PCR (RT-PCR)
      and direct sequencing of several samples. The results were correlated with other
      clinicopathological variables and patient outcome. KLK7 gene expression was
      significantly lower in breast cancer patients of low stage (I/II) (p = 0.011) and
      patients with positive progesterone receptors (p = 0.022). Survival analysis
      showed that breast cancer patients with KLK7 positive tumors have relatively
      shorter disease-free survival (DFS) and overall survival (OS) than patients with
      KLK7 negative tumors. These data suggest that KLK7 gene expression may be used as
      a marker of unfavorable prognosis for breast cancer patients.

PMID- 14691585
TI  - Diagnostic performance of complete lower limb venous ultrasound in patients with
      clinically suspected acute pulmonary embolism.
AB  - A limited ultrasound (US) confined to the popliteal and femoral veins is usually
      performed to detect deep vein thrombosis (DVT) in patients with clinically
      suspected acute pulmonary embolism (PE). Our objective was to assess the
      diagnostic accuracy of complete lower limb US examining both the proximal and
      distal veins in this setting. In this prospective study, 210 consecutive patients
      were included. Complete US was performed by independent operators and compared
      blindly with a reference strategy combining clinical probability, ventilation
      perfusion scan and pulmonary angiography to a three-month clinical follow-up.
      Simultaneously, VIDAS D-dimer (DD) assay and helical computed tomography (HCT) of
      the lungs were assessed independently and blindly. PE was present in 74 patients
      (35%). Complete US detected DVT in 91 patients (43%), proximal in 51 and distal
      in 40. Sensitivity and specificity with a 0.95 confidence interval were
      respectively 0.93 [0.85 - 0.97] and 0.84 [0.77 - 0.89]. Limited US detected DVT
      in only 46 patients (22%). Sensitivity and specificity were respectively 0.55
      [0.44 - 0.66] and 0.96 [0.92 - 0.98]. For DD they were 0.92 [0.83 - 0.96] and
      0.24 [0.17 - 0.32] and for HCT 0.84 [0.73 - 0.90] and 0.87 [0.80 - 0.92].
      Complete lower limb US has higher sensitivity and capacity to exclude PE than
      limited US, but a slightly lower specificity. Complete US results also compared
      favourably with those of HCT and DD. The utility of including this method in
      diagnostic strategies for PE needs to be assessed in cost-effectiveness analysis
      and in outcome studies.

PMID- 14691586
TI  - Skin necrosis is a clinical manifestation of low-molecular weight heparin-induced
      thrombocytopenia.

PMID- 14691587
TI  - Ventricular tachycardia as a presenting symptom in a child with thrombotic
      thrombocytopenic purpura.

PMID- 14691588
TI  - Eclampsia in a woman homozygous for the prothrombin G20210A mutation.

PMID- 14691589
TI  - Treatment of bleeding with recombinant factor VIIa in a patient with extensive
      burns.

PMID- 14691590
TI  - Integrating complete lower limb venous ultrasound into diagnostic strategies for
      pulmonary embolism: a cost-effectiveness analysis.

PMID- 14691591
TI  - Viral hepatitis: from A to E, and beyond?
AB  - Identification of hepatitis viruses A-E has enabled researchers to investigate
      the epidemiology, pathogenesis, sequelae, and possible means of prevention of
      these infections. This knowledge also provides a basis for further study of the
      pathological significance of candidate hepatitis viruses. With improvements in
      hygiene in many parts of the world, hepatitis A virus infection has decreased
      markedly. However, this success has the unintended consequence of rendering a
      large percentage of the younger population susceptible to hepatitis A virus
      infection. Fortunately, effective active immunization for hepatitis A virus is
      now available. Hepatitis B remains a common condition, especially in Asia and
      Africa which have high prevalences of chronic infection. Chronic hepatitis B
      carriers serve as reservoirs of infection for the community and are at risk of
      chronic liver disease and hepatocellular carcinoma. A mass immunization program
      in Taiwan has been remarkably successful in reducing the prevalence of chronic
      hepatitis B infection. Genotypes of the hepatitis B viruses may be associated
      with the severity of liver disease and the responses to therapies. Hepatitis C is
      another important cause of death worldwide. The infection easily becomes
      refractory and the chronicity contributes to the development of cirrhosis and
      hepatocellular carcinoma. Although no effective immunization is currently
      available for hepatitis C, it can be controlled by preventative measures and
      recently developed interferon-based treatments, especially in combination with
      ribavirin. The prevalence of hepatitis D has markedly decreased in the last
      decade and new cases are now rarely encountered. Hepatitis E is endemic in
      limited areas and travel to these areas appears to be the main risk factor for
      contracting the infection. Several new candidate hepatitis viruses have been
      identified, including GB virus-C, TT virus, and SEN virus, but none of these has
      been shown to cause hepatitis, and they may be passenger viruses.

PMID- 14691592
TI  - Androgen receptor gene polymorphism and prostate cancer in Taiwan.
AB  - BACKGROUND AND PURPOSE: The length of polymorphic CAG trinucleotide repeats in
      the polyglutamine region of the androgen receptor (AR) gene has been suggested to
      be inversely correlated with the transactivation function of the AR. An increase
      in androgen activity may be associated with prostate cancer, and ethnic
      variations in CAG repeat length may contribute to varying prostate cancer risks
      in different populations. This case-control study investigated the potential role
      of AR polymorphism in prostate cancer risk in Taiwanese. METHODS: Sixty six
      pathologically-confirmed prostate cancer patients and 104 controls were studied.
      CAG repeat polymorphism was genotyped by a polymerase chain reaction (PCR)-based
      direct sequencing method. Logistic regression was used to determine the relative
      risk of AR gene CAG number on prostate cancer risk. The associations of AR-CAG
      polymorphism with disease stage, pathologic grade, and age at diagnosis were
      assessed. AR-CAG repeat number was first treated as a continuous variable, then
      was divided into short and long groups (n < 23 vs n > or = 23) for categorical
      analysis. The extreme groups of AR-CAG distribution were also analyzed for these
      associations (n < or = 20 vs n > or = 26 and n = 21-25 vs n > or = 26). RESULTS:
      The mean number of CAG repeats in patients and controls was similar: 23.2 +/- 3.0
      (range, 15 to 31) and 22.9 +/- 3.1 (range, 15 to 31), respectively. No
      association was found between AR-CAG repeat polymorphism and disease stage (p =
      0.30), histological grade (p = 0.49), or age at diagnosis (p = 0.51). After
      adjusting for other covariates (age, body mass index, education level, smoking,
      and alcohol status), the number of AR-CAG repeats was not significantly
      associated with prostate cancer risk [odds ratio (OR) = 0.97, 95% confidence
      interval (95% CI) = 0.72 to 1.31; p = 0.84]. In categorical analysis, men with
      short CAG repeats (n < 23) did not have increased risk for prostate cancer (OR =
      0.45, 95% CI = 0.29 to 1.05) compared to those with long CAG repeats (n > or =
      23). Non-significant differences in prostate cancer risk were also found when
      comparing the extreme short group (n < or = 20) and the intermediate group (n =
      21-25) to the extreme long group (n > or = 26) [n < or = 20 vs n > or = 26: OR =
      1.00, 95% CI = 0.34 to 3.00; n = 21-25 vs n > or = 26: OR = 0.82, 95% CI = 0.37
      to 1.81]. CONCLUSIONS: The results of this study do not support an important
      effect of AR-CAG repeat polymorphism on prostate cancer risk. A large-scale study
      is needed to clarify genetic components of prostate cancer risk in the Taiwanese
      population.

PMID- 14691593
TI  - Development and verification of validity and reliability of a short screening
      instrument to identify psychiatric morbidity.
AB  - BACKGROUND AND PURPOSE: The accurate identification of minor mental disorders
      associated with depression and anxiety in non-psychiatric medical settings is an
      important component of mental health care. The present study aimed to develop a
      reliable and valid short screening tool to improve the identification of
      psychiatric morbidity. METHODS: Data from the 50-item Brief Symptom Rating Scale
      (BSRS-50) obtained from 721 medical inpatients were used to develop a short
      screening tool (BSRS-5) to identify psychiatric morbidity. The BSRS-5 comprises 5
      symptom items, selected from the BSRS-50, each of which has the highest
      correlation with the corresponding subscale score of Anxiety, Depression,
      Hostility, Interpersonal Sensitivity and Additional Symptoms in the BSRS-50.
      Various types of reliability and validity of the BSRS-5 were assessed in
      different populations, including 253 human immunodeficiency virus-1 infected
      outpatients, 257 psychiatric outpatients, 56 psychiatric inpatients, 100
      rehabilitation outpatients with chronic low back pain, 2915 university freshmen,
      and 1090 community members. RESULTS: Internal consistency (Cronbach alpha)
      coefficients of the BSRS-5 ranged from 0.77 to 0.90. The test-retest reliability
      coefficient was 0.82. Concurrent validity coefficients between the sum score of
      BSRS-5 and the General Severity Index of BSRS-50 ranged from 0.87 to 0.95.
      Choosing 6+ as the cut-off score for psychiatric cases, the rate of accurate
      classification of BSRS-5 was 76.3% (78.9% sensitivity, 74.3% specificity, 69.9%
      positive predictive value, 82.3% negative predictive value). The BSRS-5 could
      differentiate the severity of illness in psychiatric outpatients based on
      psychiatrist's ratings using the Clinical Global Impression scale, severity of
      psychopathology of psychiatric inpatients between admission and discharge, levels
      of pain indicated by 4 dimensions of the Dallas Pain Questionnaire for
      outpatients with chronic low back pain, and the severity of psychopathology
      between university students and community members with and without suicidal
      ideation. CONCLUSION: The BSRS-5 can be used to identify psychiatric morbidity in
      both medical practice and the community.

PMID- 14691594
TI  - Prediction of functional outcomes in stroke inpatients receiving rehabilitation.
AB  - BACKGROUND AND PURPOSE: Early identification of predictive factors relevant to
      functional outcomes for stroke patients is important to the establishment of an
      effective continuing care program. The objective of this study was to identify
      the predictive factors related to functional outcome at discharge after stroke
      rehabilitation therapy. METHODS: 105 first-time stroke patients admitted to the
      inpatient rehabilitation department of a university-based medical center were
      recruited for this prospective study. The functional outcomes of the patients
      were assessed at admission and at discharge using the Functional Independence
      Measure (FIM). Severity of stroke was determined using the Canadian Neurological
      Scale (CNS). Age, gender, side of hemiplegia (SIDE), type of stroke (TYPE), onset
      to admission interval (OAI), and length of rehabilitation stay (LORS) were also
      included as predictor variables. RESULTS: The mean (+/- SD) FIM score at
      discharge (76.6 +/- 26.4) correlated strongly (r = 0.78, p < 0.001) with the
      admission FIM score (56.3 +/- 24.1), moderately (r = 0.46, p < 0.001) with the
      admission CNS score (6.1 +/- 2.2), negatively (r = -0.38, p < 0.001) with age
      (63.2 +/- 12.3 years), negatively (r = -0.26, p = 0.009) with OAI (24.2 +/- 16.0
      days), and negatively (r = -0.29, p = 0.002) with LORS (34.7 +/- 16.8 days).
      Stepwise regression analyses indicated that admission FIM score, age, and
      admission CNS score were the strongest predictors of functional outcome and
      accounted for 66% of the total variation in discharge FIM total score. The
      admission FIM score was the best predictor and accounted for 61% of the
      variation. CONCLUSIONS: The findings of this study imply that the admission FIM
      scores for inpatients receiving stroke rehabilitation can be used to predict
      functional outcomes at discharge from hospital.

PMID- 14691595
TI  - Uterine artery embolization for symptomatic uterine leiomyoma and adenomyosis.
AB  - BACKGROUND AND PURPOSE: Uterine artery embolization (UAE) is increasingly
      accepted as an alternative treatment for symptomatic uterine leiomyoma and
      adenomyosis. The purpose of this study was to compare the outcomes of UAE in 3
      diagnostic categories--submucosal leiomyoma, intramural leiomyoma, and
      adenomyosis--to assist in patient selection for this relative new form of
      therapy. METHODS: The medical records of 43 patients (aged 22 to 54 years) who
      underwent UAE for symptomatic uterine leiomyoma or adenomyosis were
      retrospectively reviewed. Magnetic resonance imaging (MRI) was used for
      categorization of the patients into the 3 diagnostic categories, and also for
      objective measurement of the uterine and leiomyoma size, and subsequent imaging
      follow-up. UAE was performed using polyvinyl alcohol particles. Symptom
      improvement and complications after treatment were evaluated at gynecologist
      clinics using monthly questionnaires. The group differences in complete symptom
      resolution, uterine and leiomyoma size reduction, incidence of complications, and
      subsequent surgeries were analyzed. RESULTS: The mean duration of follow-up was
      10.9 months. Complete resolution of symptoms was achieved in 13 out of 16
      patients with submucosal leiomyoma (81%), 3 out of 15 patients (20%) with
      intramural leiomyoma (p = 0.002) and 3 out of 12 patients (25%) with adenomyosis
      (p = 0.01). The average reduction of leiomyoma size in the submucosal and
      intramural groups was 56% and 29%, respectively (p = 0.02). None of the patients
      died. Severe complications occurred in 3 of 43 patients (7%), including permanent
      amenorrhea in 2 and pelvic actinomycosis in 1 patient. The incidence of
      complications (p = 0.17) and subsequent surgery (p = 0.67) did not differ
      significantly among the 3 groups. CONCLUSIONS: UAE is an effective treatment for
      patients with symptomatic leiomyoma or adenomyosis. In this study, patients with
      submucosal leiomyoma had the best treatment outcome.

PMID- 14691596
TI  - Immunohistochemical analyses of gastric stromal tumors in Taiwanese.
AB  - BACKGROUND AND PURPOSE: Gastrointestinal stromal tumors (GISTs), identified by
      the presence of CD117 (KIT), were previously classified as gastric and intestinal
      smooth muscle tumors prior to the availability of immunohistochemical methods.
      This study evaluated the percentage of GISTs previously diagnosed as gastric
      smooth muscle tumors in our hospital during an 11-year period. METHODS: A total
      of 81 surgically resected gastric smooth muscle tumor specimens from 81 patients
      were collected from January 1986 to December 1997. Immunohistochemical studies
      were performed on these tumors with antibodies of CD34, CD117, smooth muscle
      actin (SMA), S-100, and desmin. RESULTS: Among the 81 tumors, 74 (91.4%) were
      CD117-positive and were classified as GISTs. Among the 74 GISTs, CD34 was
      positive in 72 tumors (97.3%), SMA was positive in 12 tumors (16.2%), desmin was
      positive in 5 tumors (6.7%), and S-100 was positive in 4 tumors (5.4%). The 7
      tumors classified as non-GISTs had the following immunohistochemical
      characteristics: 1 was a CD117-negative CD34-positive stromal tumor (GINST)
      [1/81, 1.2%]; 3 were schwannomas with strong S-100-positive characteristics
      (3/81, 3.7%); and 3 were smooth muscle tumors with both SMA- and desmin-positive
      status (3/81, 3.7%). No clear relationship between CD117 or CD34 expression and
      prognosis was found for these tumors. CONCLUSIONS: The majority (91.4%) of
      gastric tumors originally diagnosed as gastric smooth muscle tumors were GISTs,
      except for small groups of smooth muscle tumors and schwannomas.

PMID- 14691597
TI  - Characteristics of calcifying odontogenic cyst in Taiwanese.
AB  - BACKGROUND AND PURPOSE: Calcifying odontogenic cyst (COC) is a rare type of
      odontogenic cyst. This retrospective study analyzed the clinical, radiographic,
      and histopathologic features of COC in Taiwanese. METHODS: Ten cases of COC in 2
      male and 8 female patients with a mean age of 29 years (range, 11 to 48 years)
      treated from January 1985 to December 2002 were included. Microscopic slides,
      clinical histories, and radiographic features of these 10 COC cases were reviewed
      and analyzed. RESULTS: COCs occurred in the maxilla in 3 cases and in the
      mandible in 7 cases. COCs were associated with impacted teeth in 6 cases and with
      odontomas in 3 cases. All COCs appeared as either unilocular (9 cases) or
      multilocular (1 case) radiolucencies. In 7 cases, spotty radiopaque materials
      were scattered throughout the radiolucency. Histologically, all of the lesions
      were at least partially lined by epithelium with cuboidal to columnar basal cells
      and stellate reticulum-like suprabasal cells. Variable numbers of ghost cells,
      some of which were calcified, were observed in the lining epithelium or in the
      fibrous connective tissue wall of all 10 cases. Juxta-epithelial dentinoid was
      also found in all cases. However, proliferation of ameloblastoma-like tumor nests
      was observed in only 1 case. Based on the above histologic findings, 6 COC
      lesions were classified as simple unicystic type, 3 as unicystic odontoma
      producing type, and 1 as unicystic ameloblastomatous proliferating type.
      CONCLUSIONS: COC occurs frequently in the second and third decades and is
      commonly associated with an impacted tooth or an odontoma. It usually appears as
      a mixed radiolucent and radiopaque lesion radiographically. Simple unicystic type
      is the most common type of COC. No recurrences were found after conservative
      surgical removal in this series.

PMID- 14691598
TI  - Lymphoepithelioma-like carcinoma of the urinary bladder.
AB  - Lymphoepithelioma-like carcinomas (LELCAs) of the urinary bladder are rare. We
      report 2 such cases presenting with painless gross hematuria. The first case
      occurred in a 73-year-old man. Bladder sonography revealed a 2 x 3 cm well
      defined tumor beneath the bladder mucosa. Radical cystoprostatectomy revealed
      lymphoepithelioma-like carcinoma with perivesical soft tissue invasion. Cisplatin
      based chemotherapy was given. Computed tomography scan demonstrated no evidence
      of recurrence 26 months postoperatively. The second case occurred in a 63-year
      old man. Cystoscopy revealed a solid tumor at the bladder dome. Transurethral
      resection of bladder tumor (TUR-BT) demonstrated lymphoepithelioma-like carcinoma
      with lamina propria invasion. Tumor cells were positive for cytokeratin but
      negative for leukocyte common antigen. The patient received adjuvant chemotherapy
      due to suspicious extravesical tumor spread and high-grade tumor characteristics.
      After tumor recurrence was identified, TUR-BT was performed again and the
      surgical specimen showed superficial high-grade LELCA. After bacillus Calmette
      Guerin instillation, follow-up cystoscopy revealed no recurrence at 10 months
      postoperatively. Pure LELCA is morphologically different from transitional cell
      carcinoma and has a more favorable prognosis than high-grade, invasive bladder
      carcinoma if managed appropriately.

PMID- 14691599
TI  - Solitary fibrous tumor of the orbit.
AB  - Solitary fibrous tumor (SFT) is a mesenchymal neoplasm that most frequently
      arises in the pleura and uncommonly involves the orbit. We report the clinical
      and pathological features of an orbital SFT in a 50-year-old woman. The patient
      presented with an 8-year history of painless, slow-growing, visible mass in the
      right caruncle. Computed tomography showed a well-circumscribed, homogenous, soft
      tissue mass in the inferomedial aspect of the orbit. The tumor was totally
      excised via anterior orbitotomy. Histopathologic and immunohistochemical
      evaluation identified the mass as an SFT. The patient was free of tumor
      recurrence at 1-year follow-up. Orbital SFT can present as a visible mass in the
      caruncle and may recur if not excised completely. Long-term follow-up of patients
      is necessary because SFT may recur many years after operation.

PMID- 14691600
TI  - Type I glutaric aciduria: phenotypes and genotypes in 5 Taiwanese children.
AB  - We describe the clinical characteristics of 5 Taiwanese children with glutaric
      aciduria type I treated in a single medical center. Macrocephaly was present in 5
      of these patients, psychomotor retardation in 4, and neurological regression in
      2. Diagnosis was made prenatally in 1 patient due to an affected sibling. Low
      lysine/tryptophan formula, carnitine, and vitamin B2 were given to all patients.
      All patients disliked and could not adhere to the special formula and
      medications. Four older patients had neurological deficits prior to the start of
      the regimen. Among them, 1 died of sepsis and malnutrition. Only the prenatally
      diagnosed child did well at age 22 months. Mutational analysis, performed by
      polymerase chain reaction and sequencing, revealed an IVS10-2A>C defect in all 5
      patients, and 2 siblings were homozygous. In addition, 2 novel mutations were
      detected. We conclude that GA I might not be as rare in Taiwan as previously
      thought. IVS10-2A>C is a common mutation in the Taiwanese population, whose
      genotypes are quite different from those of Caucasians.

PMID- 14691601
TI  - Septic cavernous sinus thrombosis due to Streptococcus constellatus infection.
AB  - Adult septic cavernous sinus thrombosis (CST) due to Streptococcus constellatus
      infection has not been reported. We report a case of CST due to S. constellatus
      in a 39-year-old man who had typical presentations of septic CST including
      headache, fever, and ophthalmoplegia, with an evolving course for 10 days before
      he was sent to our emergency room. Cranial magnetic resonance imaging (MRI) study
      revealed CST, which was confirmed by cerebral angiography study. Multiple
      positive blood cultures grew viridans streptococci and further species
      identification with conventional methods, API-20 STREPT system analysis, and
      polymerase chain reaction sequencing of bacterial 16S rRNA revealed S.
      constellatus. The presence of sphenoid sinusitis in this patient was also
      demonstrated by cranial MRI study, and the presence of meningitis by meningeal
      irritation signs and inflammatory cerebrospinal fluid (CSF) findings. Chronic
      alcohol consumption for more than 10 years was the only predisposing condition to
      this infection. He had a full recovery after 6 weeks of intravenous penicillin G
      therapy (24 x 10(6) U/day). Almost complete regression of cavernous sinus lesion
      and resolution of sphenoid sinusitis were shown on follow-up cranial MRI study
      about 6 months later.

PMID- 14691602
TI  - Brain tumor presenting as anorexia nervosa in a 19-year-old man.
AB  - Slow-growing brain tumors can produce disturbances of food intake and endocrine
      dysfunction. We report a case of slow-growing midline brain tumor in a patient
      with clinical presentation of anorexia nervosa (AN). A 19-year-old man was
      referred from a general practitioner to a psychiatric clinic due to illness
      behavior and psychopathological characteristics of AN. His body weight had
      decreased from 52 kg to 40 kg within 6 months. Laboratory tests showed
      hypernatremia (160 mmol/L), adrenal insufficiency (adrenocorticotrophic hormone,
      11.4 pg/mL; 8 am cortisol, 1.4 microg/dL; 4 pm cortisol, 11.4 microg/dL) and
      hypogonadotropic hypogonadism (testosterone < 0.5 ng/mL, follicle-stimulating
      hormone < 0.1 mIU/mL, luteinizing hormone < 0.7 mIU/mL). Brain magnetic resonance
      imaging showed an extensive mass lesion at suprasellar, hypothalamic region,
      third ventricle, pineal region, lateral ventricle, and corpus callosum. Owing to
      central herniation during physical assessment, he died of unknown intracranial
      pathology. This case suggests that an intracranial tumor near the hypothalamus
      should be included in the differential diagnosis of AN. Any male adolescent with
      the clinical impression of AN should receive periodic re-evaluation, including
      neurological, endocrinological and, if necessary, neuroimaging study.

PMID- 14691607
TI  - Porcine dermal collagen (Permacol) for facial contour augmentation: preliminary
      report.
AB  - Soft tissue loss or damage can occur for various reasons, including trauma,
      surgery, and disease. Reconstruction of normal contours can be achieved by using
      either alloplastic implants or autogenous tissues. Permacol, a dermal replacement
      material derived from fibrous acellular porcine dermal collagen, has been used
      for restoration of soft-tissue contours in the face. Eight patients were treated
      with porcine collagen in an attempt to achieve a smooth contour and a natural
      feel. Clinically visible soft tissue defects were successfully covered and
      aesthetic results were satisfying. Transient swelling that subsided within a week
      was noted in all patients. Meticulous and aseptic technique is mandatory for
      Permacol use. With this limited experience, Permacol was successfully used as a
      filler implant in reconstruction of post-traumatic soft-tissue defects,
      correcting post-parotidectomy hallowing and secondary nasal surgery to cover
      osseocartilaginous irregularities. However, there is a potential risk of
      inflammation and skin contractures in thin-skinned patients when implants are
      placed superficially.

PMID- 14691608
TI  - Reconstruction of the umbilicus using a reverse fan-shaped flap.
AB  - The goal of the reconstruction for umbilical absence is to obtain a natural three
      dimensional appearance of the umbilicus with minimal operative scarring. This
      paper presents two cases of umbilical reconstruction using a reverse fan-shaped
      flap. In both cases, the umbilicus was lost during surgical procedures on the
      abdominal wall when the patients were newborns. We performed this technique in
      both cases. This technique is simple and safe. With this technique, a permanent
      umbilical depth and ring can be obtained without any complications.

PMID- 14691609
TI  - Effects of photon attenuation on the determination of cardiac volumes from
      reconstructed counts in gated blood pool SPET.
AB  - In gated cardiac blood pool single-photon emission tomography (SPET), the volume
      of a ventricle may be determined by a method that exploits the proportionality
      between that volume and the total reconstructed counts within a larger volume of
      interest that includes the actual ventricle. The present work was carried out to
      determine how the attenuation of photons modifies the reconstructed counts
      obtained with this technique, and how this affects the accuracy of volume
      determination. Furthermore, we wanted to investigate how count-based
      determination of ventricle volumes is affected by the total SPET rotation angle
      and by different arm positions. We used micro -maps derived from computed
      tomography (CT) series of nine arbitrarily chosen patients to calculate a volume
      correction factor for each cardiac volume manually drawn on the CT images. An
      anthropomorphic chest phantom was used to confirm the calculation of correction
      factors. For the regions of the ventricles contained within a CT slice through
      the central part of the heart, the left to right volume ratio needed to be
      corrected by factors of 1.21 and 1.12 for 180 degrees and 360 degrees rotation,
      respectively. When all voxels within the left and right ventricles were included,
      the required volume ratio correction factor was close to 1. However, the
      variation among patients was larger for a 180 degrees (range 0.97-1.08) than for
      a 360 degrees rotation arc (range 1.0-1.03).

PMID- 14691610
TI  - The prefrontal cortex: insights from functional neuroimaging using cognitive
      activation tasks.
AB  - This review presents neuroimaging studies which have explored the functional
      anatomy of a variety of cognitive processes represented by the prefrontal cortex
      (PFC). Overall, these studies have demonstrated that standard prefrontal
      neuroactivation tasks recruit a widely distributed network within the brain of
      which the PFC consistently forms a part. As such, these results are in keeping
      with the notion that executive functions within the PFC rely not only on anterior
      (mainly prefrontal) brain areas, but also on posterior (mainly parietal) brain
      regions. Moreover, intervention of similar brain regions in a large number of
      different executive tasks suggests that higher-level cognitive functions may best
      be understood in terms of an interactive network of specialised anterior as well
      as posterior brain regions.

PMID- 14691611
TI  - Pretargeting in tumored mice with radiolabeled morpholino oligomer showing low
      kidney uptake.
AB  - We have recently shown that accumulation in mouse kidneys of technetium-99m
      labeled phosphorodiamidate morpholinos (MORFs) increases with the number of
      cytosines in the base sequence. To improve tumor/kidney ratios in tumored mice,
      pretargeting studies were performed with a cytosine-free MORF. An 18-mer MORF (5'
      TCTTCTACTTCACAACTA) was conjugated to the anti-CEA antibody MN14 (Immunomedics)
      and administered to nude mice bearing LS174T tumors. Thereafter, the (99m)Tc
      labeled cytosine-free cMORF (5'-TAGTTGTGAAGTAGAAGA-amide-MAG(3)) was
      administered. For comparison, the identical study was repeated but with our
      original pair of 18-mer MORFs (5'-GGGTGTACGTCACAACTA-conjugated MN14 and (99m)Tc
      labeled 5'-TAGTTGTGACGTACACCC-amide-MAG(3)). Surface plasmon resonance was used
      to show that the hybridization affinities of the original and the modified pair
      of MORFs were essentially equal. Hybridization of the cytosine-free cMORF-(99m)Tc
      to MN14-MORF was demonstrated in vitro by size-exclusion high-performance liquid
      chromatography. At 3 h, kidney levels in normal mice were 2.0%ID/organ for the
      modified cMORF vs. 4.1%ID/organ for the original cMORF sequence, while at 24 h,
      these values were 0.9% vs 1.8%ID/organ. Pretargeting studies in tumored mice
      receiving 25 microg of conjugated antibody, 0.5 microg of labeled cMORF 48 h
      later, followed by imaging and sacrifice at 3 h showed that kidney levels were
      reduced using the cytosine-free cMORF. Moreover, tumor accumulation was about
      3.6%ID/g and was independent of sequence. The whole-body images clearly reflected
      the improved tumor to kidney ratios. By choosing a cytosine-free base sequence
      for pretargeting studies, kidney accumulation of cMORF-(99m)Tc was reduced
      without adversely influencing tumor accumulation. The lowering of kidney
      radioactivity levels in this way may be important to reduce toxicity to this
      organ in connection with pretargeting radiotherapy studies.

PMID- 14691613
TI  - Development and biodistribution of 188Re-SSS lipiodol following injection into
      the hepatic artery of healthy pigs.
AB  - Although intra-arterial radiotherapy with (131)I-labelled lipiodol is a useful
      therapeutic approach in the treatment of hepatocellular carcinomas, various
      disadvantages limit its use. Here we describe the development of (188)Re-SSS
      lipiodol, as well as its biodistribution in the healthy pig after injection into
      the hepatic artery. The (188)Re-SSS lipiodol was obtained after dissolving a
      chelating agent, previously labelled with (188)Re, in cold lipiodol. The
      radiochemical purity (RCP) of the labelling was checked immediately and at 24 and
      48 h. The (188)Re-SSS lipiodol was injected into the hepatic artery of six
      healthy pigs. They were killed 1, 24 and 48 h post injection, for ex vivo
      counting. An autoradiographic study was performed in three cases. (188)Re-SSS
      lipiodol was obtained with a yield of 87%+/-9.1%. The immediate RCP was 93%+/
      3.4%. This radiolabelling was reproducible and stable at 48 h in plasma: 90.6%+/
      1.5% of the activity remained in the lipiodol with an RCP of 91%+/-4%. Ex vivo
      counting confirmed the predominantly hepatic uptake and revealed weak lung and
      intestinal uptake. There was very weak urinary elimination (2.3%+/-0.5% at 48 h)
      and a slightly higher level of intestinal elimination (4.8%+/-1.9% at 48 h). The
      autoradiographic studies showed (188)Re-SSS lipiodol to be located mainly in
      sinusoids, like (131)I-lipiodol. By using the method described here, (188)Re-SSS
      lipiodol can be obtained with a very high yield and a satisfactory RCP. Its
      biodistribution in the healthy pig is in agreement with data published elsewhere
      concerning other types of radiolabelling used for lipiodol, except for the very
      weak urinary and intestinal elimination, which probably indicates better
      stability of (188)Re-SSS labelling.

PMID- 14691614
TI  - Carbamazepine markedly reduces serum concentrations of simvastatin and
      simvastatin acid.
AB  - OBJECTIVE: The aim of this study was to examine the effect of carbamazepine on
      the pharmacokinetics of orally administered simvastatin in healthy volunteers.
      METHODS: In a randomised, two-phase crossover study and a wash out of 2 weeks, 12
      healthy volunteers took carbamazepine for 14 days (600 mg daily except 200 mg
      daily for the first 2 days) or no drug. On day 15, each subject ingested 80 mg
      simvastatin. Serum concentrations of simvastatin and its active metabolite
      simvastatin acid were measured up to 24 h. RESULTS: Carbamazepine decreased the
      mean total area under the serum concentration-time curve of simvastatin and
      simvastatin acid by 75% ( P<0.001) and 82% ( P<0.001), respectively. The mean
      peak concentrations of both simvastatin and simvastatin acid were reduced by 68%
      ( P<0.01), and half-life of simvastatin acid was shortened from 5.9+/-0.3 h to
      3.7+/-0.5 h ( P<0.01) by carbamazepine. CONCLUSION: Carbamazepine greatly reduces
      the serum concentrations of simvastatin and simvastatin acid, probably by
      inducing their metabolism. Concomitant administration of carbamazepine and
      simvastatin should be avoided or the dose of simvastatin should be considerably
      increased.

PMID- 14691615
TI  - Improved determination of taurine by high-performance anion-exchange
      chromatography with integrated pulsed amperometric detection (HPAEC-IPAD).
AB  - The advantages of the high selectivity of high-performance anion-exchange
      chromatography (HPAEC) and the sensitive response of taurine at a gold electrode
      with integrated pulsed amperometric detection (IPAD) have been combined, in order
      to establish a new analytical method for its determination in real matrices.
      Potential-time settings of the potential waveform were optimized in order to get
      the highest amperometric response. The separation of taurine in milk samples was
      achieved using an alkaline eluent (100 mM NaOH) containing 1 mM Ba(OAc)(2) and a
      column temperature of 15 degrees C. The inherent merits of using a barium
      modified eluent, in terms of taurine separation and detection, are demonstrated.
      The enhancement in sensitivity under these experimental conditions makes it
      suitable for taurine determination in milk. Indeed, this method allows high
      recovery of taurine and satisfies the necessary requirements with respect to
      accuracy, repeatability and sensitivity with a detection limit of 50 nmol/L,
      which corresponds to 2.5 pmol. The taurine content in milk samples of some common
      mammals was evaluated, including human milk. In goat's milk, the taurine content
      ranged from 46 to 91 mg/L, whereas human and buffalo milk samples exhibited an
      average content of 18 mg/L and 23 mg/L, respectively.

PMID- 14691617
TI  - Fracture risk following an osteoporotic fracture.
AB  - The aim of this study was to examine the pattern of fracture risk following a
      prior fracture at the spine, shoulder or hip. We studied 1918 patients with
      fractures at these sites identified from the Department of Radiology in Malmo who
      were followed for 5 years. Poisson regression was used to compute fracture rates
      immediately after the initial fracture and at 5 years thereafter in men and women
      aged 60 or 80 years. Immediate fracture risk was higher than that of the general
      population, more markedly so at the age of 60 than at 80 years. At the age of 60
      years, the risk of hip, forearm and spine fractures were significantly increased
      following a prior spine, hip or shoulder fracture in men. A similar pattern was
      seen in women, except that the increase in risk of forearm fracture following a
      spine or hip fracture was not statistically significant. The incidence of further
      fractures at the shoulder, spine or hip fell with time after the first fracture,
      a fall that was significant for all fractures after a shoulder fracture, hip
      fracture after a spine fracture, and hip and spine fractures after a hip
      fracture. We conclude that the risk of a subsequent fracture immediately after an
      osteoporotic fracture is highest immediately after the event. This provides a
      rationale for very early intervention immediately after fractures to avoid
      recurrent fractures.

PMID- 14691616
TI  - Characterization of the effects of receptor-selective ligands in rats
      discriminating the novel antipsychotic quetiapine.
AB  - RATIONALE: Drug discrimination studies with clozapine have shown that such assays
      are of value in analysing the actions of novel antipsychotic agents in vivo.
      OBJECTIVES: To evaluate the role of specific receptors in the discriminative
      stimulus properties of the novel "atypical" antipsychotic quetiapine. METHODS:
      Rats were trained to discriminate quetiapine at 10 mg/kg and tested with a range
      of ligands, selective for specific classes of receptor. RESULTS: Full
      generalization to quetiapine was only seen with quetiapine itself (100%) and with
      the muscarinic antagonist, scopolamine (87%). Partial generalization was seen
      with the alpha(1)-adrenoceptor antagonist prazosin (63%), the presumed
      preferential dopamine D(3) receptor antagonist PNU 91194A (54%) and the 5
      HT/H(1)/M(1) antagonist cyproheptadine (55%). Minimal (<40%) or no (0%)
      generalization was seen with mepyramine (H(1) antagonist), SCH 23390 (D(1)
      antagonist), raclopride (D(2/3 )antagonist), ketanserin and MDL 100,907 (5-HT(2A
      ) antagonists), ondansetron (5-HT(3) antagonist), SB 242,084 (5-HT(2C)
      antagonist), 8-OHDPAT (5-HT(1A) agonist) yohimbine (alpha(2)-adrenoceptor
      antagonist) and the benzodiazepine, chlordiazepoxide. CONCLUSIONS: Together with
      data from a previous study (Smith and Goudie 2002) in which we observed full
      generalization to quetiapine with olanzapine, risperidone and clozapine, but not
      with typical antipsychotics (such as haloperidol) or the novel antipsychotic
      amisulpride, these data suggest that: i) the discriminative stimulus properties
      of quetiapine, like those of clozapine, probably reflect a "compound" stimulus
      which involves several classes of receptor; ii) the quetiapine cue is of value in
      analysing, and screening for, quetiapine- and clozapine-like agents in vivo; iii)
      blockade of muscarinic receptors is sufficient, although not necessary, to
      achieve full generalization to quetiapine; and iv) alpha(1-)adrenoceptors may be
      implicated in the quetiapine discriminative stimulus.

PMID- 14691619
TI  - Clinically-driven approach to improve arthroscopic techniques.
AB  - In this paper, a clinically-driven approach is introduced as the starting point
      for the improvement of arthroscopic techniques. The approach was divided into two
      phases. Phase 1 consisted of a combination of observations and discussions that
      resulted in the definition of clinically-relevant research topics. Phase 2
      consisted of an interview which aimed at analysis of the general opinion on
      arthroscopy, and which assigned a priority ranking to the topics. Six research
      topics were defined. Based on the information collected, the conclusion is that
      the surgeons are satisfied with current arthroscopic techniques. A majority gives
      priority to the optimization of cartilage treatment and to the design of a
      steerable arthroscopic cutter. A minority gives priority to the expansion of
      arthroscopic techniques. The two-phase approach was fruitful in terms of
      establishing clinical problem areas, and of involving surgeons in the technical
      improvement of arthroscopic techniques.

PMID- 14691620
TI  - Temporal expression of fibroblast growth factor receptors during primary ligament
      repair.
AB  - Following injury, it is inherently difficult to completely restore the
      biomechanical properties of ligaments. Relatively little is known about the
      cellular mechanisms controlling ligament healing. Numerous studies have
      implicated fibroblast growth factors (FGFs) as key molecules during the
      initiation of the cellular proliferation, differentiation, migration and matrix
      deposition that characterise wound healing. While current surgical emphasis
      concentrates on growth factor intervention, the role of their cognate receptors
      (FGFRs) has largely been overlooked. Following transection of the medial
      collateral ligament (MCL) in rabbits, we examined FGFR expression over a 14-day
      healing period. Using semi-quantitative RT-PCR, we observed a significant
      upregulation in FGFR2 expression after 3 days. By 7 days post injury, FGFR2
      expression fell to basal levels in line with those of FGFR1 and 3, both of which
      remained unaffected by surgical transection. These results demonstrate a role for
      FGFR2 in fibroblast and endothelial cell proliferation in damaged ligament, and
      suggest a window for FGF therapy.

PMID- 14691621
TI  - The use of intraarticular tramadol for postoperative analgesia after arthroscopic
      knee surgery: a comparison of different intraarticular and intravenous doses.
AB  - We aimed to determine the optimal dose of tramadol when administered
      intraarticularly after arthroscopic knee surgery under general anesthesia in
      patients with an American Society of Anesthesiologists (ASA) physical status
      score of I-II. When the surgical procedure was completed, patients were assigned
      to one of seven groups ( n=30 for each) in a double-blinded and randomized manner
      according to a table of random numbers. Group I received 100 mg tramadol, Group
      II received 50 mg tramadol, Group III received 20 mg tramadol and Group IV
      received 0.9% NaCl intraarticularly in 20 ml solutions. Group V received 100 mg
      tramadol, Group VI received 50 mg tramadol and Group VII received 20 mg tramadol
      intravenously. Pain was evaluated by using the Visual Analogue Scale (VAS) at 0
      min (when the patient was cooperated after extubation), 30 min, 1 h, 4 h, 6 h, 12
      h, 18 h and 24 h postoperatively. Patients were administered diclofenac sodium 75
      mg intravenously (i.m.) when they experienced pain. The intraarticular tramadol
      groups had longer duration of analgesia than i.v. tramadol groups who were
      administered the same doses (I vs V; II vs VI; III vs VII; p <0.001). Group I had
      the longest duration of analgesia ( p<0.001). Group II had a longer time to the
      first analgesic request than all other groups ( p<0.001) except Group I.
      Consequently, Group I and II needed less analgesics than other groups ( p<0.001).
      Pain scores were 0-3 on the VAS in Groups I, II and V at first assessment, in
      Groups I and II at 30 min and 1 h, and in Group I at 4 h and 6 h postoperatively
      ( p<0.01). In Group V, vomiting was more a more frequent complication than with
      other groups ( p<0.05). It is concluded that tramadol provides analgesia with a
      peripheral mechanism when administered intraarticularly. The side effects of
      intraarticular 100 mg tramadol were no more severe than those for intraarticular
      50 mg tramadol. Moreover, intraarticular 100 mg tramadol provided excellent
      analgesia after arthroscopic surgery.

PMID- 14691622
TI  - Does the Lachman testing method affect the reliability of the International Knee
      Documentation Committee (IKDC) Form?
AB  - The aim of this study was to evaluate the effect of manual and instrumented means
      of Lachman testing on the reliability of the IKDC form. A single observer
      assessed 102 patients with ACL deficiency (direct comparison group). Another
      observer assessed 35 of these patients (inter-observer group) and the initial
      observer re-assessed 47 patients (test-retest group). The Lachman test was
      performed by both manual and instrumented means and the IKDC form was completed.
      Direct comparison of the manual and instrumented Lachman test revealed
      satisfactory levels for use. Further comparison revealed satisfactory test re
      test and unsatisfactory inter-observer reliability for both means. On application
      into the IKDC form, direct comparison of both means of testing revealed
      satisfactory agreement for the overall score, but not the ligament group or
      Lachman item scores. Test-retest and inter-observer reliability testing revealed
      unsatisfactory agreement for the overall, ligament group and Lachman item scores
      for both means of testing. When using the IKDC form we recommend that a single
      observer perform the Lachman test by manual means on each occasion. If the
      original IKDC form is used only the overall score should be presented. Where the
      new IKDC form is used we recommend caution in the presentation of the examination
      section. We call into question the usefulness of the original IKDC form and the
      examination section of the new IKDC form in clinical research.

PMID- 14691624
TI  - [Anesthetic regimen for HIV positive parturients undergoing elective cesarean
      section].
AB  - OBJECTIVE: Worldwide, 50 million people are infected with the human
      immunodeficiency virus (HIV), and 43% are women. Perinatal vertical transmission
      of HIV accounts for most new pediatric cases. Elective Cesarean delivery,
      combined antiretroviral therapy perioperatively and abandonment of breast-feeding
      postoperatively reduces vertical HIV transmission. However, the incidence of
      maternal and neonatal morbidity perioperatively is relatively unknown. The goal
      of the present study was to prospectively record perioperative maternal and
      neonatal complications in the largest HIV positive collective undergoing elective
      Cesarean section with spinal anesthesia published to date. METHODS: From 1999
      2001, 54 HIV positive parturients were enrolled in this study. All parturients
      received IV zidovudine therapy (2 mg/kg body weight) perioperatively. Spinal
      anesthesia was performed using 60 mg of 4% hyperbaric mepivacaine plus 5 microg
      sufentanil intrathecally. Sensory, analgesic and motor block characteristics, the
      incidence of maternal hypotension, postoperative maternal complications as well
      as neonatal outcome were recorded. RESULTS: Short-term hypotension occurred in
      65% of the parturients. Intraoperatively, one parturient died following amniotic
      fluid embolism. In 17% of the parturients, postoperative complications headed by
      wound healing impairment, bronchitis and pneumonia requiring prolonged antibiotic
      therapy were observed. To date, after a minimum observation period of 8 months,
      only one infant (1.8%) is HIV positive. CONCLUSION: Intrathecal mepivacaine
      combined with sufentanil in HIV positive parturients undergoing elective Cesarean
      section is an appropriate anesthetic option. Postoperative maternal morbidity was
      17%. Neonatal outcome showed no evidence of neonatal depression.

PMID- 14691625
TI  - [Prediction of postoperative nausea and vomiting using an artificial neural
      network].
AB  - OBJECTIVE: Postoperative nausea and vomiting (PONV) are still frequent side
      effects after general anaesthesia. These unpleasant symptoms for the patients can
      be sufficiently reduced using a multimodal antiemetic approach. However, these
      efforts should be restricted to risk patients for PONV. Thus, predictive models
      are required to identify these patients before surgery. So far all risk scores to
      predict PONV are based on results of logistic regression analysis. Artificial
      neural networks (ANN) can also be used for prediction since they can take into
      account complex and non-linear relationships between predictive variables and the
      dependent item. This study presents the development of an ANN to predict PONV and
      compares its performance with two established simplified risk scores (Apfel's and
      Koivuranta's scores). METHODS: The development of the ANN was based on data from
      1,764 patients undergoing elective surgical procedures under balanced
      anaesthesia. The ANN was trained with 1,364 datasets and a further 400 were used
      for supervising the learning process. One of the 49 ANNs showing the best
      predictive performance was compared with the established risk scores with respect
      to practicability, discrimination (by means of the area under a receiver
      operating characteristics curve) and calibration properties (by means of a
      weighted linear regression between the predicted and the actual incidences of
      PONV). RESULTS: The ANN tested showed a statistically significant ( p<0.0001) and
      clinically relevant higher discriminating power (0.74; 95% confidence interval:
      0.70-0.78) than the Apfel score (0.66; 95% CI: 0.61-0.71) or Koivuranta's score
      (0.69; 95% CI: 0.65-0.74). Furthermore, the agreement between the actual
      incidences of PONV and those predicted by the ANN was also better and near to an
      ideal fit, represented by the equation y=1.0x+0. The equations for the
      calibration curves were: KNN y=1.11x+0, Apfel y=0.71x+1, Koivuranta 0.86x-5.
      CONCLUSION: The improved predictive accuracy achieved by the ANN is clinically
      relevant. However, the disadvantages of this system prevail because a computer is
      required for risk calculation. Thus, we still recommend the use of one of the
      simplified risk scores for clinical practice.

PMID- 14691626
TI  - [Calibration of a room air gas monitor with certified reference gases].
AB  - Photo-acoustic infrared spectrometry is considered to be the gold standard for on
      line measurement of anesthetic waste gas in room air. For maintenance of the
      precision of the measurements, the manufacturer recommends calibration of the gas
      monitor monitor every 3-12 months. We investigated whether the use of reference
      gases with analysis certificate could serve as a feasible alternative to
      commercial recalibration. We connected a multi-gas monitor type1302 (Bruel &
      Kjaer, Naerum, Denmark) to compressed air bottles containing reference gases with
      analysis certificate. Using a T-piece with a flow-meter, we avoided the entry of
      room air during the calibration phase. Highly purified nitrogen was used for zero
      calibration. The reference concentrations for desflurane, enflurane, halothane,
      isoflurane, and sevoflurane ranged from 41.6-51.1 ml/m(3) (ppm) in synthetic air.
      Since there is an overlap of the infrared absorption spectra of volatile
      anesthetics with alcohol used in operating rooms, we performed a cross
      compensation with iso-propanol (107.0 ppm). A two-point calibration was performed
      for N(2)O (96.2 and 979.0 ppm), followed by cross-compensation with CO(2). Nafion
      tubes were used in order to avoid erroneous measurements due to molecular
      relaxation phenomena. The deviation of the measurement values ranged initially
      from 0-2.0% and increased to up to 4.9% after 18 months. For N(2)O, the
      corresponding values were 4.2% and 2.7%, respectively. Thus, our calibration
      procedure using certified reference gases yielded precise measurements with low
      deterioration over 18 months. It seems to be advantageous that the precision can
      be determined whenever deemed necessary. This allows for an individual decision,
      when the gas monitor needs to be calibrated again. The costs for reference gases
      and working time as well as logistic aspects such as storage and expiration dates
      must be individually balanced against the costs for commercial recalibration.

PMID- 14691623
TI  - [Toxicology of local anesthetics. Clinical, therapeutic and pathological
      mechanisms].
AB  - Regardless of their specific physico-chemical properties and chemical structures,
      all local anaesthetic agents block neuronal voltage-gated sodium channels, and
      thus suppress conduction in peripheral nerves. Since these ion channels
      ubiquitously appear in excitable membranes, systemic accumulation of local
      anaesthetic agents may affect the functional integrity of these structures.
      Clinically, local anaesthetic-induced systemic toxicity results in central
      nervous and cardiovascular malfunction. With regard to CNS toxicity, symptoms
      which are largely drug-independent appear in a characteristic biphasic sequence.
      Nevertheless, the plasma levels necessary to provoke these symptoms are to a
      large extent agent-specific. Initially, these toxic mechanisms are due to a
      selective blockade of cortical inhibitory neurons, which enables the formation of
      seizure potentials within subcortical structures. With high cerebral drug levels,
      however, excitatory neurons are also increasingly blocked, resulting in coma,
      apnoeic episodes and circulatory failure. Direct cardiac effects of local
      anaesthetics can be divided into (i) stereospecific inhibition of intracardial
      conduction and (ii) unspecific inhibition of myocardial energy supply and ion
      channels. The corresponding spectrum of symptoms is not uniform and may range
      from extreme bradycardia, (malignant) ventricular arrhythmia to refractory
      cardiac arrest. Local tissue toxicity has to be strictly delimited from systemic
      toxicity and allergies, respectively, which are mainly caused by aminoester
      agents. Local anaesthetics may cause neuronal and striated muscle injury at the
      site of injection. With regard to (central) neurotoxicity, "transient neurologic
      symptoms" and "cauda equina syndrome" have been increasingly recognised. However,
      the clinical relevance of local anaesthetic-induced myotoxicity is still
      controversly discussed. In order to avoid systemic accumulation of local
      anaesthetic agents, several safety procedures have to be considered during the
      application of these drugs. The treatment of systemic toxicity is strictly
      dependent on the expression of symptoms. However, hypoxia and acidotic episodes
      must be avoided and must be treated aggressively.

PMID- 14691627
TI  - [The Narcotrend monitor. Development and interpretation algorithms].
AB  - The Narcotrend performs an automatic interpretation of the electroencephalogram
      (EEG) during anaesthesia. The classification algorithms have been developed on
      the basis of visually classified EEG epochs. The classification scheme which was
      used for these visual assessments has its origin in sleep analysis and was
      adapted for the EEG during anaesthesia. From the awake state to very deep
      anaesthesia, 15 stages (A, B(0-2), C(0-2), D(0-2), E(0-2), F(0-1)) are
      distinguished. The transformation of these stages into a numerical scale from 100
      to 0 is a further refinement for a differentiated presentation of EEG effects.
      For the automatic classification multivariate discriminant functions are used.
      Age-related changes of the EEG were incorporated. The device contains functions
      for the identification of artifacts. The EEG can be recorded from a frontal
      channel using standard ECG electrodes, other electrode positions and types can be
      chosen. The device has been clinically and scientifically validated.

PMID- 14691628
TI  - [Does chewing gum have consequences for anesthesia? A case report].
AB  - Chewing gum is a common habit. Based on two cases of esophageal obstruction
      during induction of general anesthesia, the importance of chewing gum for
      anesthesiology is outlined. The dangers of chewing gum result from obstruction of
      the trachea and oesophagus but complications may also result from stimulated
      production of gastric juice with a risk of consecutive regurgitation and
      aspiration. In the case of an obstacle in the oesophagus when inserting a
      nasogastric tube, an obstruction by a mass of chewing gum should be considered.
      Although the literature provides differing statements concerning the volume and
      acidity of gastric juice after chewing gum, the use of chewing gum should be
      included in preanesthetic NPO rules.

PMID- 14691629
TI  - [Epicardial echocardiography intraoperative diagnostic utility to assess valve
      function].
AB  - Epicardial echocardiography has been available since the early 1970s as an
      intraoperative diagnostic modality to assess ventricular and valvular function.
      With this technique, an ultrasonic transducer is placed directly on the
      epicardial surface of the heart, following sternotomy and pericardiotomy. Under
      the guidance of the cardiac anesthesiologist, the surgeon places the transducer
      so that the desired views of cardiac structures and great vessels can be
      obtained. The anesthesiologist performs the acquisition, analysis and
      interpretation of the echocardiographic images. Despite the feasibility of
      epicardial echocardiography, transesophageal echocardiography (TEE) has emerged
      over the last two decades as the main form of intraoperative echocardiography.
      Although TEE allows continuous monitoring of cardiac and valvular function
      without interruption of the surgical procedure, placement of a TEE probe may be
      difficult or contraindicated in some patients. In such cases, epicardial
      echocardiography may be the optimal ultrasonographic imaging modality to assess
      ventricular and valvular function during cardiac surgery. We describe the use of
      epicardial echocardiography for intraoperative assessment of valvular function in
      two patients where TEE was either contraindicated or probe placement could not be
      performed safely. The first patient underwent surgical repair of the mitral valve
      for severe mitral regurgitation. After weaning the patient from cardiopulmonary
      bypass (CPB), epicardial echocardiography was used to confirm successful
      reconstruction of the valve and to exclude residual mitral regurgitation. The
      second patient was scheduled for coronary artery bypass grafting (CABG). Prior to
      the initiation of CPB, the presence of moderate aortic stenosis was confirmed
      using Doppler echocardiography via an epicardial approach.

PMID- 14691630
TI  - [Preserved spontaneous breathing during partial liquid ventilation. Results of
      experimental animal studies and their clinical implications].
AB  - Controlled mechanical ventilation (CMV) may contribute to impaired hemodynamics
      in patients with respiratory failure. It is rational to assume that hybrid
      modalities of mechanical ventilation have fewer hemodynamic side-effects when
      spontaneous respiratory activity is allowed during the application of positive
      airway pressure. Partial liquid ventilation (PLV) has been shown to improve gas
      exchange in subjects with severe alveolar lung disease. We have shown that
      spontaneous respiratory efforts during proportional assist ventilation (PAV) is
      possible in experimental animals without lung disease whose lungs are partially
      filled with perfluorocarbons. In another series of experiments we demonstrated
      that PLV improves oxygenation and lung compliance in adult rabbits with severe
      surfactant deficiency, and in rabbits with meconium aspiration. In animals with
      meconium aspiration mortality, work of breathing and the degree of lung injury,
      as assessed by histological analysis, were reduced. In another two series of
      animals with and without surfactant deficiency spontaneous breathing supported by
      PAV was associated with increased cardiac output, stroke volume and oxygen
      transport, as compared to CMV after pharmacologically induced muscle paralysis.
      An increased arterial and venous pH in animals with surfactant deficiency during
      spontaneous breathing supported by PAV suggests improved tissue perfusion.
      Furthermore, gas exchange was improved during spontaneous breathing supported by
      PAV as compared to CMV and muscle paralysis.

PMID- 14691632
TI  - [Liability of the anesthesiologist for medical records. Lead ruling by the
      Austrian High Court and comparison with the Austrian and German legal position].

PMID- 14691631
TI  - [Melagatran and ximelagatran. Pharmacologic characteristics and anesthesiological
      aspects].
AB  - Melagatran is a direct inhibitor of thrombin and-like its oral prodrug
      ximelagatran-a newly developed dipetide with high antithrombotic efficacy. They
      present a linear dose-response, a short plasma half-life and the therapeutic
      range may be advantageous compared with classic anticoagulants such as heparins
      or vitamin K antagonists. The results of clinical studies for prevention and
      treatment of thromboembolic complications are encouraging. The use of melagatran
      and ximelagatran will gain significance in the perioperative management, thus
      being of particular importance for anaesthesiology and critical care medicine in
      the near future.

PMID- 14691633
TI  - Regional brain cooling induced by vascular saline infusion into ischemic
      territory reduces brain inflammation in stroke.
AB  - The neuroprotective effect of hypothermia has long been recognized. Use of
      hypothermia for stroke therapy, which is currently being induced by whole body
      surface cooling, has been largely limited because of management problems and
      severe side effects (i.e., pneumonia). Our recent studies have demonstrated the
      significant therapeutic value of local brain cooling in the ischemic territory
      prior to reperfusion in stroke. The goal of this study was to determine if
      cerebral local cooling infusion could reduce stroke-mediated brain injury by
      inhibiting inflammatory responses. A hollow filament was used to block the middle
      cerebral artery (MCA) for 3 hours, and then to locally infuse the ischemic
      territory with 6 ml cold saline (20 degrees C) for 10 min prior to 48-h
      reperfusion. This cold saline infusion significantly ( P<0.01) reduced
      temperature of the MCA supplied territory (in cerebral cortex from 37.2+/-0.1
      degrees C to 33.4+/-0.4 degrees C, in striatum from 37.5+/-0.2 degrees C to
      33.9+/-0.4 degrees C), with the hypothermia remaining for at least 45 min after
      reperfusion. Consequently, significant ( P<0.01) reductions in endothelial
      expression of intracellular adhesion molecule-1 (ICAM-1), the key step for
      inflammatory progress, as well as leukocyte infiltration, were evident in both
      cortex and striatum after reperfusion. As a control, ischemic rats received the
      same amount of cold saline systemically through a femoral artery. A mild
      hypothermia was induced in the cerebral cortex (35.3+/-0.2 degrees C) but not in
      the striatum (36.8+/-0.2 degrees C). The reduced cortical temperature returned to
      normal within 5 min. Brain temperature in ischemic rats perfused locally with
      saline at 37 degrees C remained normal. Intensive expression of ICAM-1 and
      accumulation of leukocytes was observed in ischemic control groups without brain
      cooling infusion. In conclusion, brain hypothermia induced by local pre
      reperfusion infusion ameliorated brain inflammation from stroke.

PMID- 14691635
TI  - Traumatic abdominal wall hernia: an unusual bicycle handlebar injury.
AB  - Traumatic hernia of the abdominal wall is rare. The mechanism of injury can be
      severe such as a motor vehicle accident or relatively minor such as a fall onto a
      bicycle handlebar. In children traumatic abdominal wall hernia can occur even
      after relatively minor trauma and these cases typically have no associated intra
      abdominal injury. We report a traumatic hernia of the anterior abdominal wall in
      a 7-year-old boy following a fall from a bicycle. A review of the literature
      revealed only nine similar reports. The presence of localised pain, bruising, and
      a reducible swelling or a cough impulse suggests the diagnosis. Primary repair
      with prosthetic material is the preferred treatment.

PMID- 14691634
TI  - Intestinal aganglionosis associated with the Waardenburg syndrome: report of two
      cases and review of the literature.
AB  - The authors report two cases of the rare concurrence of intestinal aganglionosis
      and Waardenburg syndrome in Japanese infants. The patients were a 1-month-old
      girl and a 3-month-old boy at diagnosis, and both of them had either short
      segment or ultra-short segment aganglionosis. A review of 48 cases in the
      literature showed that the extent of the aganglionic segment is quite variable,
      from nearly total to ultra-short. The clinical features of aganglionosis in
      Waardenburg syndrome would appear to bear similarity in sex ratio and the extent
      of aganglionosis with those of Hirschsprung's disease associated with Ondine's
      curse, another type of neurocristopathy.

PMID- 14691636
TI  - Is adrenomedullin involved in the pathophysiology of persistent pulmonary
      hypertension of the newborn?
AB  - Although adrenomedullin (ADM) is a potent vasodilating peptide reported to play a
      possible role in the mechanisms of fetal lung differentiation and maturation, the
      ADM blood level in fetuses and in neonates with persistent pulmonary hypertension
      (PPHN) and pulmonary hypoplasia is not known. Therefore, we examined 15 patients
      with PPHN: 10 with congenital diaphragmatic hernia, four with congenital cystic
      adenomatoid malformation of the lung, and one with misalignment of pulmonary
      vessels with alveolar capillary dysplasia. Eight surgical patients with neonatal
      conditions such as intestinal atresia served as controls. Blood samples were
      drawn from the umbilical artery and vein at birth, and arterial blood was drawn
      from patients with PPHN on the 3rd and 6th days after birth. Plasma levels of ADM
      were measured by radiometric assay. Plasma levels of ADM in the umbilical artery
      and vein were elevated in patients with PPHN compared with controls, and in all
      groups the levels in the umbilical vein were higher than those in the umbilical
      artery. The arterial levels in patients with poor prognoses were elevated on the
      3rd and 6th days after birth compared with those in survivors. These results
      indicate that ADM may be involved in the pathophysiology of PPHN and in the
      mechanisms of lung differentiation and/or maturation.

PMID- 14691637
TI  - Expression profiling of favorable and unfavorable neuroblastomas.
AB  - Neuroblastomas show remarkable biological heterogeneity, resulting in favorable
      or unfavorable outcomes. To survey the differences in gene expression profiles
      between favorable and unfavorable neuroblastomas, we analyzed ten favorable
      neuroblastoma samples from patients whose tumors consequently regressed or
      matured and ten unfavorable tumor samples from patients who consequently died of
      disease using the microarray technique. In each sample, total RNA was labeled
      with Cy3 or Cy5 in reverse-trancriptase reaction and hybridized with our original
      microarray prepared with a cDNA library of human fetal brain. Microarray analysis
      revealed that 43 genes, including MYCN, hTERT, NME1 and cell cycle regulatory
      protein-coding genes, were highly expressed in unfavorable neuroblastomas, while
      another 80 genes were detected as highly expressed in favorable tumors, including
      neuronal differentiating genes and apoptotic inducing genes. Among favorable
      neuroblastoma samples, highly expressing genes in regressing tumors were
      different from those in maturing tumors. Expression profiling data revealed the
      existence of up-regulated and down-regulated gene clusters in favorable and
      unfavorable tumors. This cluster analysis is a powerful procedure to distinguish
      unfavorable tumors from favorable tumors as well as regressing tumors from
      maturing tumors among favorable tumors. The information obtained from expression
      profiling would clarify the key genes for cell growth, regression or maturation
      of neuroblastoma cells, and these genes will become diagnostic and therapeutic
      targets in human neuroblastoma in the future.

PMID- 14691638
TI  - Endosurgical procedures for pediatric solid tumors.
AB  - The aim of this study was to evaluate the advantages and complications of
      endosurgical procedures for benign and malignant pediatric solid tumors.
      Endosurgical techniques of biopsy and excision were used for diagnosis and
      treatment of solid tumors, respectively. Since July 1997, a total of 24 biopsies
      and 24 excisions have been performed laparoscopically for neuroblastoma ( n=24),
      ovarian solid tumors ( n=10) and other tumors. Seventeen biopsies and six
      excisions were performed for abdominal neuroblastoma, while ten excisions were
      performed for ovarian tumor. In these patients, the length of the operation,
      blood loss, time to start postoperative feeding, time to start postoperative
      chemotherapy and length of hospital stay were evaluated and compared to the those
      of the open surgery group. Furthermore, intra- and postoperative complications
      were analyzed in all patients of both groups. The length of the hospital stay and
      time to start postoperative feeding were significantly shorter in the group of
      patients who underwent endosurgical procedures for either abdominal neuroblastoma
      or ovarian tumor when compared to the open procedure group. The time to start
      postoperative chemotherapy was shorter only in the abdominal neuroblastoma group.
      The procedure for two patients undergoing endosurgical tumor excision had to be
      converted to open surgery due to large tumor size. Two weeks after thoracoscopic
      excision of a dumb bell-type neurofibroma, one patient underwent open repair of
      the dura mater because of leakage of cerebrospinal fluid. There were no port-site
      recurrences in any tumor types. Endosurgical procedures for solid tumors are
      effective and minimally invasive. However, better indicators are needed for their
      implementation in order to prevent complications and subsequent conversions to
      open procedures.

PMID- 14691639
TI  - Massive debris in the intrahepatic bile ducts in choledochal cyst: possible cause
      of postoperative stone formation.
AB  - We investigate the incidence, treatment, and implications of intrahepatic bile
      duct (IHBD) dilatation debris in 42 patients with choledochal cyst treated over a
      recent 8-year period. Mean age at cyst excision was 6.9 years, and mean follow-up
      period was 5.4 years. Intraoperative endoscopy (IOE) was performed at the time of
      cyst excision using a pediatric cystoscope, which identified IHBD debris in 11/42
      (26.2%), and massive debris in 4/42 (9.5%). In all cases, IHBD debris was
      successfully washed out with normal saline through the cystoscope. There was no
      postoperative IHBD stone formation or cholangitis except for one case of
      cholangitis in a patient undergoing chemotherapy for acute myelocytic leukemia.
      Debris left in the IHBD during cyst excision is probably one of the primary
      causes of postoperative IHBD stone formation and can be prevented by washing
      during IOE.

PMID- 14691640
TI  - Normal galenic drainage of the deep cerebral venous system in two cases of vein
      of Galen aneurysmal malformation.
AB  - INTRODUCTION: Vein of Galen aneurysmal malformations (VGAM) are assumed to be
      related to the persistence of the embryonic median prosencephalic vein of
      Markowski, which does not involute in cases of VGAM and becomes the venous
      collector of the shunt, characteristic of the malformation. The arterial feeders
      of VGAMs are all primitive meningeal arteries present during the embryonic period
      of the constitution of the malformation. It has also been assumed that the
      internal cerebral veins were absent in patients presenting with VGAM. There is no
      clear evidence indicating, however, that the deep venous structures cannot
      develop normally. CASE REPORTS: We report on two cases of VGAM in which
      superselective retrograde transvenous catheterization and MRI demonstrated that
      normal internal cerebral veins were draining into the aneurysmal vein of Galen.
      CONCLUSIONS: It is conceivable that, as in our patients, this drainage pattern is
      only angiographically detectable via selective retrograde transvenous drainage.
      The possibility of such normal deep galenic venous drainage must be considered in
      VGAM management, as it may imply occurrence of adverse effects when the
      malformation is occluded on the venous side.

PMID- 14691641
TI  - Benign focal epilepsy with onset in infancy in a patient with 18q-syndrome.
AB  - CASE REPORT: The 18q-syndrome is sometimes associated with epilepsy. We report a
      child with a 18q deletion who showed the typical manifestations of the syndrome.
      In addition, she had benign focal epilepsy with onset in infancy characterized by
      complex partial seizures with a frequency from 1 to 20 per day. This type of
      epilepsy is a rare condition and this is the first report of benign focal
      epilepsy with onset in infancy in a child with 18q-syndrome. The EEGs performed
      during sleep showed low-voltage spikes over the fronto-central region of the left
      hemisphere. The magnetic resonance imaging of the brain was normal. CONCLUSION:
      In conclusion, benign focal epilepsy with onset in infancy could be a condition
      associated with 18q-syndrome.

PMID- 14691642
TI  - Morning glory syndrome and basal encephalocele.
AB  - BACKGROUND: Morning glory syndrome (MGS) is a congenital optic disc dysplasia
      often associated with craniofacial anomalies, especially basal encephalocele.
      Clinical presentations are varied and often occult. CASE REPORT: We describe a
      case of bilateral MGS associated with basal encephalocele that was detected by
      chance when treatment was sought for respiratory distress. CONCLUSIONS: MGS and
      basal encephalocele should always be suspected in cases of midline deficiencies,
      particularly when ophthalmic signs of strabismus or poor vision are present. CT
      and MRI should be performed to delineate the extent of the lesion and a complete
      hormone screening should be carried out to exclude pituitary deficiency. The
      pathogenesis of MGS and basal encephalocele are unknown; however, it is thought
      to occur during the 5th week of embryonic development.

PMID- 14691643
TI  - Predictive genetic testing in urology: ethical and social issues.
AB  - In order to maximize the benefits of predictive genetic testing in urology, the
      potential ethical and social risks must be identified and minimized. Necessary
      steps include providing adequate information for patients and families; preparing
      them to receive test results; maintaining confidentiality to avoid social stigma
      and discrimination; preserving the principal of solidarity to provide assurances
      of medical care and social support for persons at risk of genetic illness; and
      avoiding inappropriate social pressure to prevent the birth of at-risk
      individuals. Health professionals must play a significant role in helping
      individuals, families, and society in general to make sound testing decisions and
      policy.

PMID- 14691646
TI  - Balancing analytical performance and medical reasoning: is carryover a critical
      issue in estimating low white blood cell numbers in bone marrow/stem cell
      transplant recipients?

PMID- 14691647
TI  - Problems associated with high prevalence of multidrug-resistant bacteria in
      patients with community-acquired infections.

PMID- 14691648
TI  - Optimizing outcomes with antimicrobial therapy through pharmacodynamic profiling.
AB  - In patients with infection, improving the probability of positive treatment
      outcomes depends on optimizing the interactions between the host, pathogen, and
      drug. In this setting, optimal regimens must be utilized which not only maximize
      effectiveness in a specific patient, but also minimize the development of
      microbial resistance. The probability of achieving a specifically targeted
      antimicrobial exposure can be assessed using Monte Carlo simulation, a technique
      which integrates an agent's in vitro potency distribution (i.e., minimum
      inhibitory concentrations [MICs]) with the pharmacokinetic profile. The targeted
      pharmacodynamic parameters assessed by this technique include the ratio of peak
      concentration (C(max)) to MIC (C(max) : MIC); the ratio of the area under the
      plasma concentration-time curve (AUC) to MIC (AUC : MIC), and the time the drug
      concentration exceeds the MIC (T > MIC). Some antimicrobials, e.g., the
      aminoglycosides, are most effective/bactericidal when they have a high C(max) :
      MIC ratio; others, e.g., the fluoroquinolones, are more effective when the AUC :
      MIC ratio is high. In both of these scenarios, organism eradication is
      concentration-dependent, and the therapeutic goal is to maximize drug exposure.
      Like the fluoroquinolones, the efficacy of telithromycin, a newly developed
      ketolide, is most related to the AUC : MIC ratio. Outcome for other agents, such
      as the beta-lactams, is best predicted by the T > MIC; in this case, organism
      eradication is time-dependent, and the therapeutic goal is to optimize the
      duration of antimicrobial exposure. This article discusses how the use of
      currently available antimicrobials can be optimized through an appreciation of
      pharmacodynamic profiling.

PMID- 14691649
TI  - Pretreatment of Pseudomonas aeruginosa with a sub-MIC of imipenem enhances
      bactericidal activity of neutrophils.
AB  - The influence of the pretreatment of Pseudomonas aeruginosa strain O1 (PAO-1)
      with a sub-minimum inhibitory concentration (MIC) of imipenem on bactericidal
      activity, phagocytosis, the production of oxygen radical intermediates, and the
      induction of apoptosis in murine peritoneal neutrophils, as well as the catalase
      activity in the bacteria in comparison with that of ceftazidime-treated bacteria
      were studied. Bacteria treated with imipenem at (1/4) MIC were killed at
      significantly higher rates by neutrophils than ceftazidime-treated and nontreated
      bacteria. However, antibiotic-treated bacteria showed similar numbers of bacteria
      phagocytized neutrophils to those in untreated bacteria. Imipenem pretreatment of
      bacteria led to an increase in the production of oxygen radical intermediates by
      neutrophils and the inhibition of neutrophilic apoptosis following incubation,
      whereas these features did not occur in neutrophils incubated with nontreated and
      ceftazidime-treated bacteria. The catalase activity of bacteria was not
      suppressed by pretreatment with either antibiotic at (1/4) MIC. These findings
      suggest that the exposure of P. aeruginosa to a sub-MIC of imipenem enhances the
      susceptibility of the bacteria to neutrophilic killing and effectively modifies
      the physiological activities of neutrophils, but does not decrease bacterial
      catalase activity. These actions may account for the postantibiotic leukocyte
      enhancement (PALE) effect of a sub-MIC of imipenem in the host.

PMID- 14691650
TI  - Enhancement of antimicrobial effects of various antibiotics against methicillin
      resistant Staphylococcus aureus (MRSA) by combination with fosfomycin.
AB  - The present study was designed to evaluate the efficacy of fosfomycin used in
      combination with drugs that were found to be less effective against methicillin
      resistant Staphylococcus aureus (MRSA). Twelve different antibiotics were tested
      against 32 strains of MRSA isolated from the wounds of burn patients admitted to
      the Burn Unit at Tokyo Women's Medical University Hospital. These antibiotics -
      fosfomycin (FOM), flomoxef sodium (FMOX), imipenem (IPM), cefotiam (CTM),
      cefmetazole (CMZ), ampicillin (ABPC), sulbactam/cefoperazone (SBT/CPZ),
      minocycline (MINO), ofloxacin (OFLX), and panipenem (PAPM) - were used either
      alone or in combination. Arbekacin (ABK) and vancomycin (VCM) were used for
      comparing efficacy in controlling bacterial growth. While both ABK and VCM were,
      as expected, found to be effective in suppressing in vitro bacterial growth, all
      ten other agents when used alone were found to be ineffective. In contrast, these
      agents, when used in combination with FOM, showed remarkable efficacy against all
      strains of MRSA tested. Based upon the in vitro findings, it is suggested that
      FOM, in combination with other antimicrobial agents, such as IPM, PAPM, CMZ, and
      SBT/CPZ may be used instead of ABK and/or VCM to curtail the emergence of
      Staphylococcus aureus strains that are resistant to these latter two drugs.

PMID- 14691652
TI  - Effects of anti-inflammatory drugs on convulsant activity of quinolones: a
      comparative study of drug interaction between quinolones and anti-inflammatory
      drugs.
AB  - Quinolones have been reported to possess potent convulsant activity, which is
      enhanced when they are administered concurrently with anti-inflammatory drugs. To
      define the individual drug interactions of quinolones with anti-inflammatory
      drugs, we studied the convulsant activity of six quinolones with or without 13
      anti-inflammatory drugs and 3 analgesic/antipyretic drugs in mice.
      Intraventricular injections of norfloxacin (NFLX), enoxacin (ENX), ciprofloxacin,
      lomefloxacin (LFLX), levofloxacin, and gatifloxacin induced convulsions in mice
      in a dose-dependent manner. Concurrent administration of biphenylacetic acid
      strongly enhanced the convulsant activity of NFLX, ENX, and LFLX. Flurbiprofen
      also strongly enhanced the activity of NFLX and ENX, and ketoprofen strongly
      enhanced the activity of ENX. However, mefenamic acid, piroxicam, tenoxicam,
      meloxicam, etodolac, sulpyrine, isopropylantipyrine, and acetaminophen had no
      effect on the convulsant activity of quinolones. These results suggest that each
      quinolone has an individual drug interaction with each anti-inflammatory drug. It
      was suggested that we should know which anti-inflammatory drugs enhance the
      convulsant activity of individual quinolones, and which quinolone has no/weak
      drug interaction with different anti-inflammatory drugs when these drugs are used
      concurrently for the treatment of patients with infectious diseases.

PMID- 14691651
TI  - Frequency of alterations in the GyrA subunit of DNA gyrase and the ParC subunit
      of topoisomerase IV in 19 clinical isolates of Neisseria gonorrhoeae in Tokyo in
      2002.
AB  - The frequency of alterations in the GyrA subunit of DNA gyrase and the ParC
      subunit of topoisomerase IV in 19 clinical isolates of Neisseria gonorrhoeae
      obtained in Tokyo in 2002 was studied. The frequencies of GyrA and ParC mutations
      in these 19 isolates were 100% (19 of 19) and 84.2% (16 of 19), respectively, and
      these results were 1.48-fold (100%/67.6%) and 3.58-fold (84.2%/23.5%) higher,
      respectively, than the frequencies reported in 1998 in 68 isolates obtained in
      Fukuoka during the period from 1992 to 1996. Isolates with increasing numbers of
      mutations were more resistant not only to levofloxacin but also to other
      antibiotics. The 50% and 90% minimum inhibitory concentrations (MICs) to
      levofloxacin during the period from 1995 to 1996 were 0.063 and 1 micro g/ml, and
      they increased to 4 and 8 micro g/ml, respectively, in the present study. All 19
      cases of gonoccocal urethritis in the present study were cured with a single
      intramuscular injection of 2 g spectinomycin.

PMID- 14691653
TI  - Beta-lactam resistance in Streptococcus mitis isolated from saliva of healthy
      subjects.
AB  - The purpose of this study was to examine the percentage of Beta-lactam-resistant
      streptococcal carriers in healthy adults, and to investigate the relationships
      among minimum inhibitory concentrations (MICs) of Beta-lactams, alterations in
      the penicillin-binding protein genes ( pbp genes), and the affinity of penicillin
      binding proteins (PBPs) for ampicillin (ABPC) in Streptococcus mitis. We also
      compared numbers of surviving bacteria at various ABPC concentrations in both
      ABPC-susceptible and -resistant S. mitis strains. The percentages of subjects
      carrying ABPC- and cefaclor (CCL)-resistant streptococci were 52% (27 of 52
      subjects) and 100%, respectively. S. mitis, including both antibiotic-susceptible
      and -resistant strains, were classified into five groups according to the pbp
      gene mutations that resulted in alterations of the deduced amino-acid sequence in
      the homology boxes of PBPs. All ABPC-resistant strains showed alterations in
      PBP1A, 2X, and 2B, while no or only PBP2X alterations were detected in the
      susceptible strains. These results suggest that the accumulation of pbp gene
      mutations is strongly related to the MIC of ABPC for S. mitis. In the resistant
      strains, the affinity of PBPs for ABPC was reduced in comparison with that in the
      susceptible strains, and the bactericidal effect of ABPC was also reduced.
      Therefore, we should be aware of conditions such as infective endocarditis that
      are caused by Beta-lactam-nonsusceptible streptococci in the normal oral flora.

PMID- 14691654
TI  - Usefulness of bronchial lavage for the diagnosis of pulmonary disease caused by
      Mycobacterium avium-intracellulare complex (MAC) infection.
AB  - To evaluate the usefulness of bronchial lavage for the diagnosis of pulmonary
      disease due to Mycobacterium avium-intracellulare complex (MAC) infection, we
      examined the clinical records and bacteriologic findings of patients admitted to
      our hospital between 1999 and 2002 who fulfilled the 1997 American Thoracic
      Society (ATS) criteria for MAC pulmonary infection. Bronchoscopic examinations
      were performed in those patients with MAC pulmonary disease who showed negative
      sputum smears for mycobacteria on 3 consecutive days ( n = 14) or who could not
      expectorate sputum ( n = 2). The bronchial lavage sample was smear-positive for
      acid-fast bacilli in 8 of the 16 patients (50.0%), polymerase chain reaction
      (PCR)-positive for MAC in 10 of 15 (66.7%), and culture-positive for MAC in 15 of
      16 (93.7%). The brushing sample was positive for MAC in 5 of 14 patients (35.7%),
      and transbronchial lung biopsy (TBLB)-positive for MAC in 2 of 5 (40.0%). MAC was
      isolated by culture of bronchial lavage samples in a higher percentage of
      patients than that in whom MAC was isolated by sputum culture, and we could make
      an early diagnosis of MAC pulmonary disease based on the smear and PCR results
      for bronchial lavage samples. Bronchial lavage is useful to screen sputum smear
      negative patients suspected of having MAC pulmonary disease.

PMID- 14691655
TI  - A prospective comparison of the effect of interferon-alpha and interferon-beta
      treatment in patients with chronic hepatitis C on the incidence of hepatocellular
      carcinoma development.
AB  - To investigate differences in the effect of interferon (IFN) -alpha and IFN-beta
      treatment for hepatitis C on hepatocellular carcinoma (HCC) development, we
      prospectively followed 351 consecutive patients (median age, 56.6 years; mean
      follow-up, 5.7 +/- 2.6 years) with chronic hepatitis C virus (HCV) viremia. Of
      260 IFN-alpha and 91 IFN-beta treated patients, 17 (6.5%) and 4 (4.4%),
      respectively, developed HCC. Virological response (VR) was defined as persistent
      HCV RNA disappearance from serum, and biochemical response (BR) as persistent
      alanine aminotransferase (ALT) normalization after treatment. No significant
      between-group differences in HCC development were found between those with and
      without VR. Although the HCC development rate in patients without BR was
      significantly higher than that in patients with BR in the IFN-alpha group (11.4%
      and 0.8%; P << 0.05), no significant difference was found in the IFN-beta group
      (6.3% and 2.3%). Similar rates of HCC development were found in patients with
      chronic HCV viremia treated with either IFN-alpha or IFN-beta.

PMID- 14691656
TI  - Puerperal intrauterine infection caused by Edwardsiella tarda.
AB  - Edwardsiella tarda infection is uncommon and has been reported to be associated
      with pet reptiles and the ingestion of raw fish. The majority of the infections
      occur as gastrointestinal disorders in immunocompromised hosts. We report a case
      of puerperal intrauterine E. tarda infection in a patient with no history of
      predisposing illness or of the recent ingestion of raw fish; this is the first
      such report. The patient complained of high fever, lower abdominal pain, and
      increasing amounts of malodorous genital discharge; these signs and symptoms
      responded well to intravenous antimicrobial chemotherapy.

PMID- 14691657
TI  - Isolation of Helicobacter cinaedi from blood of an immunocompromised patient in
      Japan.
AB  - We report the isolation of Helicobacter cinaedi (previously called "
      Campylobacter-like organism") from the blood of an immunosuppressed Japanese
      patient receiving immunosuppressive therapy after renal transplantation. The
      identification of H. cinaedi was based on the findings of microscopic
      examinations, biochemical properties, and 16S rRNA gene nucleotide sequences. H.
      cinaedi bacteremia should be considered as one of the critical infectious
      diseases in immunocompromised patients, and the sequencing of 16S rRNA may be a
      useful method to confirm the identification of this organism.

PMID- 14691658
TI  - Meningitis caused by Enterococcus gallinarum in patients with
      ventriculoperitoneal shunts.
AB  - Vancomycin-resistant enterococci have recently emerged as significant nosocomial
      pathogens. Here we describe two Japanese patients, a 57-year-old man and a 12
      year-old boy, with ventriculoperitoneal shunts for hydrocephalus who developed
      meningitis caused by vancomycin-resistant Enterococcus gallinarum. The infection
      of the central nervous system in these two patients may have been associated with
      E. gallinarum derived from the gut. Removal of the shunts and antimicrobial
      treatment promoted apparent improvement in these patients. The risk factors and
      management of vancomycin-resistant enterococcal infections in the central nervous
      system are discussed.

PMID- 14691659
TI  - Pseudomembranous colitis caused by toxin A-negative/toxin B-positive variant
      strain of Clostridium difficile.
AB  - We report the first case of pseudomembranous colitis (PMC) due to a toxin A
      negative, toxin B-positive strain (toxin A variant strain) of Clostridium
      difficile in Japan. The toxin A variant strain of C. difficile is capable of
      causing PMC and is undetectable in clinical laboratories that use only toxin A
      immunoassays for C. difficile testing. If C. difficile-associated diarrhea is
      clinically suspected and toxin A is not detected, then the possibility of a toxin
      A variant strain should be considered, and further diagnostic testing, such as
      polymerase chain reaction (PCR) analysis for the detection of C. difficile toxin
      genes should be performed.

PMID- 14691660
TI  - Severe strongyloidiasis complicated by meningitis and hydrocephalus in an HTLV-1
      carrier with increased proviral load.
AB  - We report a 47-year-old Japanese man who was a human T-cell leukemia virus type 1
      (HTLV-1) carrier with strongyloidiasis, and who was born in an area endemic for
      both Strongyloides stercoralis ( S. stercoralis) and HTLV-1. He presented with
      edema of both legs. Laboratory examination on admission revealed hypoalbuminemia,
      and S. stercoralis rhabditiform larvae were found by stool microscopy. Purulent
      meningitis, which was suspected to be due to disseminated strongyloidiasis,
      developed during the first and second treatment for S. stercoralis infection.
      After the meningitis was alleviated, hydrocephalus with gait disturbance
      developed, and these features were attenuated by a ventriculo-peritoneal shunt.
      Impaired immunity and increased HTLV-1 proviral load, with an increased titer of
      HTLV-1 antibody, were observed in this patient. These results suggest that HTLV-1
      proviral load and/or antibody titer of HTLV-1 can be used for the identification
      of carriers who are at increased risk of developing severe strongyloidiasis among
      those patients who are infected with both S. stercoralis and HTLV-1.

PMID- 14691661
TI  - Penetration of oral telithromycin into female genital tissues.
AB  - To estimate the potential efficacy of telithromycin in the treatment of
      gynecological infections, a pharmacokinetic study was conducted in 13 Japanese
      subjects. Telithromycin was administered orally, at a dose of 600 mg, to patients
      undergoing hysterectomy, 3.0 to 7.5 h prior to the hysterectomy. At surgical
      operation, cubital venous blood, uterine arterial blood, vaginal cervix uteri
      (portio vaginalis), supravaginal uterine cervix, uterine endometrium, uterine
      myometrium, oviduct, and ovary specimens were collected separately. The blood and
      tissue concentrations of telithromycin were measured with a bioassay, using
      Micrococcus luteus ATCC 9361 as the test organism. The concentrations of
      telithromycin in these tissues and their proportions in relation to that in
      cubital venous blood (in parentheses) were as follows: cubital venous blood,
      0.119 to 1.270 mg/l; uterine arterial blood, 0.111 to 1.230 mg/l; vaginal cervix
      uteri (portio vaginalis), 0.356 to 1.850 mg/kg (1.324 to 5.640), supravaginal
      uterine cervix, 0.376 to 4.520 mg/kg (1.108 to 16.807), uterine endometrium,
      0.234 to 5.300 mg/kg (0.975 to 12.185), uterine myometrium, 0.309 to 5.050 mg/kg
      (1.288 to 19.832), oviduct, 0.375 to 5.550 mg/kg (1.563 to 10.000); and ovary,
      0.495 to 5.250 mg/kg (1.835 to 6.851). From these results, it was concluded that
      the concentrations of telithromycin in female genital tissues are generally
      higher than those in blood. Taking the antimicrobial spectrum of telithromycin
      into consideration, it was suggested that telithromycin could potentially be a
      good candidate for the treatment of gynecological infections, including cases
      associated with sexually transmitted diseases.

PMID- 14691662
TI  - Frequency of alterations in the GyrA subunit of DNA gyrase and the ParC subunit
      of topoisomerase IV in 19 clinical isolates of Neisseria gonorrhoeae in Tokyo in
      2002.

PMID- 14691664
TI  - Intimal hyperplasia and hemodynamic factors in arterial bypass and arteriovenous
      grafts: a review.
AB  - Stenosis at the graft-vein junction caused by intimal hyperplasia (IH) is the
      major cause of failure of vascular access grafts used for hemodialysis. There is
      a strong relationship between hemodynamic factors and formation of IH. The
      hemodynamic pattern and the location of IH are different in arterial bypass
      grafts (ABGs) compared with arteriovenous grafts (AVGs). In an ABG, end-to-side
      anastomosis of the expanded polytetrafluoroethylene graft and artery produces
      hemodynamic changes around the junction. IH develops at the arterial floor and
      the toe and heel of the distal anastomosis. Low shear stress and oscillating
      shear forces at the arterial floor and the heel plus a high wall sheer stress
      (WSS) gradient at the toe probably promote IH development. Compliance mismatch
      between the graft and artery causes turbulence that may contribute to IH
      formation. The blood flow rate in AVGs is 5-10 times greater than that in ABGs.
      High flow causes turbulence that injures endothelial cells and eventually results
      in IH. The peak WSS in AVGs is about 6 N/m(2), much higher than that in ABGs.
      Excessively high WSS may effect IH formation in AVGs. Several venous cuff or
      patch anastomotic designs have been used in attempts to regulate hemodynamic
      factors in grafts. In ABGs, these designs appear to help decrease IH formation.
      In AVGs, however, they generally have not improved patency rates. In a high-flow
      system such as an AVG, more drastic changes in anastomotic design may be
      required.

PMID- 14691663
TI  - A novel passive functional MRI paradigm for preoperative identification of the
      somatosensory cortex.
AB  - The purpose of this study was to assess the feasibility of a novel passive
      functional magnetic resonance imaging (fMRI) paradigm for activation analysis of
      the somatosensory cortex utilizing a specifically designed conductor for
      electrical stimulation of the median and tibial nerves. Thirteen healthy
      volunteers underwent electrical stimulation of these nerves with defined
      frequencies and intensities in a block-designed fashion. Electrical stimuli were
      applied by two custom-designed magnetoelectrically protected coaxial leads,
      taking into account the technical difficulties of the application of electrical
      current in the fMRI environment. Activation effects were analysed in real-time
      mode and validated by statistical parametric mapping. The shielded conductors
      suppressed electromagnetically derived artefacts nearly completely. The
      measurements revealed maximum cortical activation when applying a stimulation
      frequency of 3 Hz and an intensity of 3 mA above motor threshold. Simultaneous
      stimulation of both the median and tibial nerves enhanced identification of the
      central region significantly. A standardized setup for the clinical environment
      was evolved. With this passive paradigm, the identification of the somatosensory
      cortex was possible in all evaluated cases. The presented technical setup and
      paradigm is a reliable and fast method for preoperative identification of the
      somatosensory cortex and may represent a feasible paradigm for generation of pre-
      and intraoperative fMRI in functionally disabled patients.

PMID- 14691665
TI  - Hybrid bioartificial liver: establishing a reversibly immortalized human
      hepatocyte line and developing a bioartificial liver for practical use.
AB  - Recently, much attention has been attracted by a novel therapy for liver failure
      using a hybrid bioartificial liver (BAL) support device that incorporates living
      liver cells. Researchers in various fields have considered the following cells
      for potential use in BALs: human embryonic stem (ES) cells; somatic stem cells;
      differentiated tissue cells; and cells derived from tissues of different animal
      species, particularly from the pig. With their pluripotency, human ES cells are
      extremely useful, and many research groups are joining the race to develop BALs.
      One such effort involves the breeding of transgenic pigs to overcome interspecies
      barriers. Recent reports suggest, however, that porcine endogenous retrovirus may
      infect human tissues, and clinical application of transgenic pigs has become a
      controversial issue. To avoid such risks, we recommend that researchers adopt a
      reversible immortalization system that uses the Cre-loxP site-specific
      recombination reaction targeting human hepatocytes in their final differentiated
      state. This system has allowed us to establish a safe human hepatocyte line that
      is capable of differentiation at low cost and on a large scale. We are also
      designing and developing an artificial liver module made of a combination of
      hollow fibers and nonwoven fabrics. The objective of this review article is to
      report our therapeutic strategy, which aims at the earliest possible introduction
      of the treatment of liver failure using BALs.

PMID- 14691666
TI  - Clinical study of biocompatibility between open and closed heparin-coated
      cardiopulmonary bypass circuits.
AB  - The objective of this study was to investigate the difference between the closed
      circuit system and the open circuit system in clinical heparin-coated
      cardiopulmonary bypass (CPB) circuits with a centrifugal pump. We evaluated the
      coagulation, fibrinolysis, and inflammatory response in valvular heart surgery.
      Nineteen patients were assigned at random to a group for the closed circuit
      system or the open circuit system. This is the first report on the effect of a
      closed circuit in valvular surgery. We measured the platelet count, white blood
      cell count, plasma fibrinogen concentration, thrombin-antithrombin III complex,
      plasmin-Alpha2 plasmin inhibitor complex, D-dimer, interleukin-6, polymorphic
      neutrophil-elastase, and the plasma free hemoglobin. Blood samples were collected
      before the start of perfusion, 15 and 60 min after the start of perfusion, 60 min
      after the administration of protamine, and 1 day after the operation. During the
      perfusion, coagulation, fibrinolysis, and inflammatory responses were activated;
      however, no significant differences between the two groups were noted. In this
      clinical investigation with suction and the cell saving system, the closed
      circuit was not found to be superior to the open circuit with regard to
      biocompatibility.

PMID- 14691667
TI  - Expression of mRNA for growth factors and extracellular matrix proteins after
      injury to cultured peritoneal cells: does the healing process contribute to
      peritoneal ultrastructural alteration?
AB  - The purpose of this study was to investigate the possibility that healing
      processes following repeated injury by nonphysiological dialysate play a
      significant role in the pathogenesis of peritoneal ultrastructural alteration,
      mediated by the production of growth factors and extracellular matrix proteins
      (ECM). To test a possible mechanism for peritoneal membrane alteration, we
      investigated whether chemically injured peritoneal mesothelial cells and
      fibroblasts upregulate their production of growth factors and ECM as a
      consequence of the healing process. Using 1 N NaOH, circular wounds of uniform
      surface area were made in monolayers of subconfluent rat peritoneal mesothelial
      cells (RPMC) and peritoneal fibroblasts (RPFB). At 0, 24, and 72 h after
      wounding, changes in mRNA expression of transforming growth factor-beta 1 (TGF
      Beta1), b-FGF, HGF, VEGF, and FN were semiquantified by reverse transcription
      polymerase chain reaction. Nonwounded monolayers of RPMC and RPFB were used as
      controls with mRNA expression being determined at the same times. For RPMC, TGF
      Beta1, HGF, b-FGF, and FN mRNA gradually increased up to 72 h postwounding to 1.5
      fold, 1.6-fold, 1.3-fold, and 2.1-fold of the control levels, respectively. A
      significant increase was only observed for TGF-Beta1, while VEGF showed the least
      change with time. For RPFB, HGF, b-FGF, VEGF, and FN mRNA expression were
      slightly suppressed compared to control levels up to 72 h postwounding. TGF
      Beta1, however, increased markedly above control expression levels by the end of
      the wound healing process. The production of profibrotic growth factors by
      mesothelial cells in response to injury may represent a mechanism whereby
      fibroblast activation, resulting in fibroblast hyperplasia and excessive
      extracellular matrix accumulation, culminates in alteration of the peritoneal
      membrane ultrastructure.

PMID- 14691668
TI  - In vitro and ex vivo blood compatibility study of 2-methacryloyloxyethyl
      phosphorylcholine (MPC) copolymer-coated hemodialysis hollow fibers.
AB  - To identify the advantages of 2-methacryloyloxyethyl phosphorylcholine (MPC)
      copolymer-coated polysulfone (PSf) hollow fibers for hemodialyzer and hemofilter
      minimodules with hollow fibers were made and blood compatibility was evaluated in
      vitro and ex vivo. Three types of hollow fibers, i.e., pure PSf (no additives),
      PSf alloyed with poly(1-vinyl-2-pyrrolidone) (PVPy), and PSf coated with the MPC
      copolymer, were processed in wet conditions. Commercially available hollow fibers
      (APS) were used as a control sample. The PSf hollow fibers have a condensed
      structure. A porous structure was observed when the PVPy was alloyed before wet
      processing, and no effect of the innercoated MPC copolymer on the porous
      structure was observed. One-tenth-sized minimodules of the conventional
      hemodialyzer were fabricated with 200 fibers each. The solute permeability of the
      hollow fibers was evaluated using 10% bovine serum in a buffer solution
      containing cytochrome C, which is a model protein of Beta(2)-microglobulin. After
      circulation for 2.5 h, the solute permeability of APS and PVPy-alloyed PSf hollow
      fibers decreased to 50% compared with their initial values. In contrast, the
      value for the hollow fibers innercoated with the MPC copolymer maintained its
      initial level. The inner surface of the dialysis membranes was observed with a
      transmission electron microscope and a layer of adsorbed protein on the PSf, APS,
      and PVPy-alloyed PSf hollow fibers was observed, but not on the MPC copolymer
      coated fibers. Blood cell adhesion was then evaluated by circulation of whole
      rabbit blood without any anticoagulant ex vivo. Many adherent cells were observed
      on the PVPy-alloyed PSf hollow fibers; however, blood cells did not adhere or
      aggregate on the MPC copolymer-coated hollow fibers. From these results, we
      concluded that the in-situ coating of MPC copolymer on PSf hollow fibers is
      effective in preventing blood coagulation and maintaining the solute permeability
      of the fibers.

PMID- 14691669
TI  - Effects of vascular endothelial growth factor released from cultured dermal
      substitute on proliferation of vascular endothelial cells in vitro.
AB  - Allogeneic cultured dermal substitute (CDS) was prepared by culturing fibroblasts
      on a two-layered spongy matrix of hyaluronic acid and atelocollagen. CDS can be
      cryopreserved and transported to other hospitals in a frozen state. The present
      study was designed to analyze the amounts of vascular endothelial growth factor
      (VEGF) released from fibroblasts in fresh and cryopreserved CDS and to
      investigate the effects of this VEGF on proliferation of vascular endothelial
      cells in vitro. The culture medium used in preparing CDS (fresh CDS culture
      medium sample) was collected and stored at -30 degrees C for the quantitative
      analysis of VEGF. After thawing cryopreserved CDS, it was recultured in a culture
      medium for 1 week. The culture medium used was collected and stored at -30
      degrees C for quantitative analysis of VEGF. The amounts of VEGF released from
      the fresh and cryopreserved CDS into the culture medium were about 610 pg/ml and
      640 pg/ml, respectively. This finding suggests that the cryopreserved CDS retains
      its ability to release VEGF. Immunohistological analysis indicated that some of
      the VEGF adhered to the matrix. Human vascular endothelial cells were cultured in
      medium mixed with the fresh or cryopreserved CDS culture medium sample.
      Proliferation of vascular endothelial cells was enhanced by increasing the
      concentration of both CDS culture medium samples. When antihuman VEGF antibody
      was added to the culture medium, the proliferative activity of vascular
      endothelial cells was reduced. These findings confirm that VEGF released from CDS
      promotes proliferation of vascular endothelial cells.

PMID- 14691670
TI  - Development of a biohybrid simulator for absorption and biotransformation
      processes in humans based on in vitro models of small intestine and liver
      tissues.
AB  - The scope of conventional cytotoxicity tests does not usually include various
      metabolic processes in humans. We therefore developed a physiologically based
      multicompartment perfusion coculture system (biohybrid simulator) using a Caco-2
      cell monolayer on a semipermeable membrane and a microcarrier-based three
      dimensional culture of Hep G2 cells to mimic absorption across the small
      intestine and biotransformation in the small intestine and the liver. Stable
      operation enabled the maintenance of various activities of both cell types for at
      least 4 days. Cocultivation improved the growth of Hep G2 cells and enhanced the
      cytochrome P450 1A1/2 capacities of both cell lines. When benzo[a]pyrene (BaP)
      was introduced to the apical side of the Caco-2 cell layer, the enhanced P450
      capacities produced a larger amount of BaP-7,8-hydrodiol, an immediate precursor
      to the highly reactive ultimate toxicant of BaP, BaP-7,8-dihydrodiol-9,10
      epoxide. This led to initially retarded and later stronger expression of BaP
      toxicity in the coculture system than in pure culture, which agreed well with the
      largest time integral of the concentration (area under curve) of BaP-7,8
      hydrodiol in the Hep G2 cell compartment of the coculture system. Because this
      kind of system can reproduce such complicated phenomena, including those derived
      from organ-to-organ interactions, it is useful as a new in vitro experimental
      system to help elucidate unknown mechanisms involved in final toxicity in humans
      and to develop physiologically based pharmacokinetic numerical simulation models.

PMID- 14691671
TI  - Noncardiogenic pulmonary edema induced by a molecular adsorbent recirculating
      system: case report.
AB  - Noncardiogenic pulmonary edema is a well-recognized manifestation of acute lung
      injury which has been related, among others, to blood or blood-product
      transfusion, intravenous contrast injection, air embolism, and drug ingestion. We
      describe two cases of noncardiogenic pulmonary edema after use of a molecular
      adsorbent recirculating system, a cell-free dialysis technique. Patients in this
      series presented at our institution to be evaluated for liver transplantation.
      Subsequently, they developed an indication for the molecular adsorbent
      recirculating system. Two patients of 30 (6.6%) treated with the molecular
      adsorbent recirculating system for acute-on-chronic liver failure and intractable
      pruritus had normal chest X-rays before treatment and developed severe pulmonary
      edema, in the absence of cardiogenic causes, following use of the molecular
      adsorbent recirculating system. For each patient we reviewed the history of blood
      or blood-product transfusion, echocardiograms if available, daily chest X-rays,
      and when available pre- and postmolecular adsorbent recirculating systemic blood
      pressure, central venous pressure, pulmonary arterial pressures, cardiac output,
      cardiac index, systemic vascular resistance index, and arterial blood gas. Our
      data suggest that the molecular adsorbent recirculating system may cause
      noncardiogenic pulmonary edema, possibly by an immune-mediated mechanism.

PMID- 14691672
TI  - Active site modeling in copper azurin molecular dynamics simulations.
AB  - Active site modeling in molecular dynamics simulations is investigated for the
      reduced state of copper azurin. Five simulation runs (5 ns each) were performed
      at room temperature to study the consequences of a mixed
      electrostatic/constrained modeling for the coordination between the metal and the
      polypeptide chain, using for the ligand residues a set of charges that is
      modified with respect to the apo form of the protein by the presence of the
      copper ion. The results show that the different charge values do not lead to
      relevant effects on the geometry of the active site of the protein, as long as
      bond distance constraints are used for all the five ligand atoms. The distance
      constraint on the O atom of Gly45 can be removed without altering the active site
      geometry. The coordination between Cu and the other axial ligand Met121 is
      outlined as being flexible. Differences are found between the bonds of the copper
      ion with the two apparently equivalent N(delta1) atoms of His46 and His117. The
      overall findings are discussed in connection with the issue of determining a
      model for the active site of azurin suitable to be used in molecular dynamics
      simulations under unfolding conditions.

PMID- 14691673
TI  - Improvement of comparative modeling by the application of conserved motifs
      amongst distantly related proteins as additional restraints.
AB  - Protein comparative modeling has useful applications in large-scale structural
      initiatives and in rational design of drug targets in medicinal chemistry. The
      reliability of a homology model is dependent on the sequence identity between the
      query and the structural homologue used as a template for modeling. Here, we
      present a method for the utilization and conservation of important structural
      features of template structures by providing additional spatial restraints in
      comparative modeling programs like MODELLER. We show that root mean square
      deviation at C(alpha) positions between the model and the corresponding
      experimental structure and the quality of the models can be significantly
      improved for distantly related systems by utilizing additional spatial restraints
      of the template structures. We demonstrate the influence of such approaches to
      homology modeling during distant relationships in understanding functional
      properties of protein such as ligand binding using cytochrome P450 as an example.

PMID- 14691674
TI  - Molecular dynamics simulation of hepatitis C virus IRES IIId domain: structural
      behavior, electrostatic and energetic analysis.
AB  - The dynamic behavior of the HCV IRES IIId domain is analyzed by means of a 2.6-ns
      molecular dynamics simulation, starting from an NMR structure. The simulation is
      carried out in explicit water with Na+ counterions, and particle-mesh Ewald
      summation is used for the electrostatic interactions. In this work, we analyze
      selected patterns of the helix that are crucial for IRES activity and that could
      be considered as targets for the intervention of inhibitors, such as the
      hexanucleotide terminal loop (more particularly its three consecutive guanines)
      and the loop-E motif. The simulation has allowed us to analyze the dynamics of
      the loop substructure and has revealed a behavior among the guanine bases that
      might explain the different role of the third guanine of the GGG triplet upon
      molecular recognition. The accessibility of the loop-E motif and the loop major
      and minor groove is also examined, as well as the effect of Na+ or Mg2+
      counterion within the simulation. The electrostatic analysis reveals several ion
      pockets, not discussed in the experimental structure. The positions of these ions
      are useful for locating specific electrostatic recognition sites for potential
      inhibitor binding.

PMID- 14691675
TI  - Usefulness of graphical invariants in quantitative structure-activity
      correlations of tuberculostatic drugs of the isonicotinic acid hydrazide type.
AB  - Quantitative structure-activity relationship (QSAR) studies have been performed
      for a series of 2-substituted isonicotinic acid hydrazides utilizing theoretical
      molecular descriptors. 223 topological (topostructural and topochemical) indices
      along with seven geometrical descriptors were computed for the prediction of
      antibacterial activity against Mycobacterium tuberculosis. Ridge-regression
      models assessed by cross-validated R2 have been formulated, and a comparative
      study on the relative effectiveness of physicochemical vis-a-vis theoretical
      molecular descriptors performed. The models developed clearly indicate the
      supremacy of structure-activity over property-activity relationships in the
      current study and can be used to evaluate the potential tuberculostatic activity
      of other INH derivatives, real or hypothetical.

PMID- 14691677
TI  - Malocclusion and caries prevalence: is there a connection in the primary and
      mixed dentitions?
AB  - The purpose of this epidemiological cross-sectional study was to determine the
      prevalence of malocclusion and caries in children and to investigate whether a
      relationship exists between prevalence of caries and studied malocclusion. The
      study consisted of 8,864 preschool and schoolchildren with primary dentitions
      (mean age 4.5 years) and mixed dentitions (mean age 8.9 years). 1997 WHO dental
      caries criteria were applied to both groups. The existence of an increased caries
      risk was deducted from the dmft and DMFT indices related to age. Malocclusion in
      primary and mixed dentitions was classified into seven types. Fifty-seven percent
      of all children had some form of malocclusion. Prevalence of malocclusion
      increased and was significantly greater in the mixed dentition sample (p < 0.001)
      than in the primary dentition sample. Seventy-four percent of children with
      primary dentitions and 23% of children with mixed dentitions had zero dmft and
      DMFT scores. Mean dmft indices in subjects with primary and mixed dentitions were
      1.02 and 1.53, respectively. No positive correlation between prevalence of caries
      and malocclusion could be established in the sub sample with primary teeth only.
      However, statistically significant parallelism in prevalence of malocclusion and
      caries were found for posterior cross-bite (p= 0.050) and mandibular overjet (p=
      0.013) in children with mixed dentitions.

PMID- 14691679
TI  - JBMM then and now.

PMID- 14691678
TI  - Investigation of protonatable residues in Rhodothermus marinus caa3 haem-copper
      oxygen reductase: comparison with Paracoccus denitrificans aa3 haem-copper oxygen
      reductase.
AB  - The Rhodothermus marinus caa(3 )haem-copper oxygen reductase contains all the
      residues of the so-called D- and K-proton channels, with the notable exception of
      the helix VI glutamate residue (Glu278(I) in Paracoccus denitrificans aa(3)),
      being nevertheless a true oxygen reductase reducing O(2) to water, and an
      efficient proton pump. Instead, in the same helix, but one turn below, it has a
      tyrosine residue (Tyr256(I), R. marinus caa(3) numbering), whose hydroxyl group
      occupies the same spatial position as the carboxylate group of Glu278(I), as
      deduced by comparative modelling techniques. Therefore, we proposed previously
      that this tyrosine residue could play an important role in the proton pathway. In
      this article we further study this hypothesis, by investigating the equilibrium
      thermodynamics of protonation in R. marinus caa(3), using theoretical
      methodologies based on the structural model previously obtained. Control
      calculations are also performed for the P. denitrificans aa(3) oxygen reductase.
      In both oxygen reductases we find several residues that are proton active (i.e.,
      that display partial protonation) at physiological pH, some of them being redox
      sensitive (i.e., sensitive to the protein redox state). However, the caa(3
      )Tyr256(I) is not proton active at physiological pH, in contrast to the aa(3)
      Glu278(I) which is both proton active at physiological pH and shows a high redox
      sensitivity. In R. marinus caa(3) we do not find any other residues in the same
      protein zone that can have this property. Therefore, there are no putative D
      channel residues that are proton active in this oxidase. The protonatable
      residues of the K-channel are much more functionally conserved in both oxygen
      reductases than the same type of residues in the D-channel. Two (Tyr262(I) and
      Lys336(I), caa(3) numbering) out of three protonatable K-channel residues are
      proton active and redox sensitive in both proteins.

PMID- 14691680
TI  - Cloning and characterization of three PHEX homologues in Drosophila.
AB  - Inactivating mutations and/or deletions of PHEX ( Phosphate-regulating gene with
      Homologies to Endopeptidase on the X chromosome) are responsible for X-linked
      hypophosphatemic rickets in humans. In the present study, three Drosophila PHEX
      homologues (dPHEX-1, -2, -3) were isolated by the screening of a Drosophila cDNA
      library and expressed sequence tag (EST) database. The structural region
      involving motif II: (456)WMXXXTKXXAXXK(468) (numbered according to human PHEX),
      motif VI: (602)WW(603), and motif VIII: (746)CXLW(749) was conserved in the dPHEX
      family. Zinc-coordinating motifs (HEFTH and GENIADNGG) were also conserved in the
      dPHEX family. All three dPHEX genes were expressed during all stages of
      Drosophila development. The expression of dPHEX-1 was suppressed by dietary
      phosphate deprivation, but the expression of dPHEX-2 and that of dPHEX-3 were not
      affected. In-situ hybridization showed a ubiquitous distribution of dPHEX-1 and
      dPHEX-2, while dPHEX-3 was highly expressed in the larval brain. In an analysis
      of subcellular localization, dPHEX-1 was localized to intracellular organelles
      and dPHEX-3 was localized predominately in the plasma membrane of Drosophila
      embryonic S2 cells. Homozygosity of a dPHEX-1 mutation, a transposon insertion in
      the dPHEX-1 promoter region, was completely lethal at an early stage of embryonic
      development. The present study indicates that three homologues are likely
      involved in the phosphate homeostasis of Drosophila.

PMID- 14691681
TI  - Calcitonin in human odontoclasts regulates root resorption activity via protein
      kinase A.
AB  - Calcitonin is a known inhibitor of osteoclastic bone resorption, but it remains
      uncertain whether calcitonin also regulates human odontoclastic activity,
      particularly during the physiological process of root resorption. In this study,
      we examined the expression of calcitonin receptors in human odontoclasts and the
      effect of calcitonin on root resorption, using immunocytochemistry and reverse
      transcription-polymerase chain reaction (RT-PCR). Actin-ring formation was used
      to assess cytostructural changes during resorption activity. Our results show
      that calcitonin receptors are expressed in human odontoclasts freshly isolated
      from deciduous teeth of the periodontal region. Calcitonin inhibited actin-ring
      formation and resorption activity. This calcitonin-induced inhibition was
      mimicked by forskolin and dibutyryl-adenosine 3',5'-cyclic monophosphate (db
      cAMP), which are protein kinase A (PKA) activators, but not by phorbol 12
      myristate 13-acetate, a protein kinase C activator. Pretreatment with adenosine
      3',5'-cyclic monophosphothioate Rp diastereomer (Rp-cAMPS), a PKA inhibitor,
      suppressed the calcitonin-induced inhibition of actin-ring formation. These
      results indicate that calcitonin receptor activation suppresses odontoclastic
      root resorption via PKA, a signaling pathway different from that in human
      osteoclasts.

PMID- 14691682
TI  - Parathyroid hormone inhibits the expression of membrane-type matrix
      metalloproteinase-1 (MT1-MMP) in osteoblast-like MG-63 cells.
AB  - Parathyroid hormone (PTH) can stimulate bone resorption by increasing the
      activity and the number of osteoclasts in bone tissue by several mechanisms.
      Recently, osteoblast-derived membrane-type matrix metalloproteinase-1 (MT1-MMP)
      has been implied to play an important role in the process of bone resorption by
      degrading bone matrix. In the present study, we observed the effects of PTH (1
      34) on MT1-MMP production, and the role of the protein kinase A (PKA) and protein
      kinase C (PKC) pathways in the regulation of MT1-MMP in cultures of human
      osteoblast-like MG-63 cells. By Northern blot and Western immunoblot analysis, we
      found, unexpectedly, that PTH (1-34) inhibited MT1-MMP mRNA and protein
      expression in a dose- and time-dependent manner in MG-63 cells. The PKA
      antagonist H-89 blunted PTH (1-34)-mediated decreases in MT1-MMP protein
      synthesis. Forskolin, a PKA agonist, decreased MT1-MMP expression, which was
      similar to the action of PTH on MT1-MMP expression, in MG-63 cells.
      Staurosporine, a PKC inhibitor, also blocked the inhibition by PTH. We suggest
      that both the PKA and PKC pathways are involved in MT1-MMP downregulation by PTH.
      Furthermore, we found that PTH (1-34) induced the expression of receptor
      activator of nuclear factor (NF)-KappaB ligand (RANKL) mRNA in a dose- and time
      dependent manner in MG-63 cells, and this effect of PTH on RANKL mRNA expression
      was nearly parallel to the effects of MT1-MMP downregulation, implying a
      correlation between MT1-MMP and RANKL expression. Our findings suggest that the
      decreased MT1-MMP expression induced by PTH may be involved in RANKL signaling in
      osteoblasts, and may play a role in the activation of bone resorption.

PMID- 14691683
TI  - Effects of treadmill exercise on bone mass, bone metabolism, and calciotropic
      hormones in young growing rats.
AB  - The aim of the present study was to examine the effects of exercise on bone mass,
      bone metabolism, and calciotropic hormones in young growing rats. Twenty 6-week
      old female Wistar rats were randomized into the following four groups with 5
      animals each: 7 weeks of exercise, 7 weeks of sedentary control, 11 weeks of
      exercise, and 11 weeks of sedentary control. The exercise regimen consisted of
      running on a treadmill at 25 m/min for 1 h each day on 5 days a week. After each
      period of exercise, the bone mineral content (BMC) of the tibia and fifth lumbar
      spine was measured by dual-energy X-ray absorptiometry, using a Lunar DPX-L
      instrument. The femoral length and levels of bone markers and calciotropic
      hormones were also assessed. Seven and 11 weeks of exercise increased the serum
      osteocalcin and 1,25-dihydroxyvitamin D(3) levels, and decreased the serum
      parathyroid level. Seven weeks of exercise decreased the urinary
      deoxypyridinoline level, and 11 weeks of exercise increased the serum alkaline
      phosphatase level and decreased the serum tartrate-resistant acid phosphatase
      level. As a result, 7 and 11 weeks of exercise increased the femoral length and
      tibial BMC, but did not alter the lumbar BMC. The present study demonstrates that
      treadmill exercise stimulates bone formation and suppresses bone resorption,
      increases the serum 1,25-dihydroxyvitamin D(3) level, and decreases the serum
      parathyroid hormone level, resulting in an increase in bone mass with stimulation
      of longitudinal bone growth, especially at weight-bearing sites, in young growing
      rats. Further studies with long-term exercise may be needed to obtain a positive
      effect on the lumbar BMC.

PMID- 14691684
TI  - Reappraisal of Katsuragi calcium study, a prospective, double-blind, placebo
      controlled study of the effect of active absorbable algal calcium (AAACa) on
      vertebral deformity and fracture.
AB  - A prospective, double-blind, placebo-controlled study of the effect of
      supplementation with 900 mg/day of calcium, as active absorbable algal calcium
      (AAA Ca) or calcium carbonate (CaCO(3)), on lumbar bone mineral density (BMD)
      carried out in elderly inpatients with osteoporosis at Katsuragi Hospital was re
      evaluated in terms of the effects on vertebral fracture and spondylotic
      deformity. In addition to the already reported increase in lumbar BMD, AAA Ca was
      found to inhibit new occurrence of vertebral fracture. Intra-individual
      variations in L(1)-L(4) BMD (expressed by the coefficient of variation,
      indicating the degree of spondylotic deformity, were also inhibited significantly
      in the group supplemented with AAA Ca (group A), but not in group B (supplemented
      with CaCO(3)), from the level in the placebo-supplement group (group C) after 18
      months of supple-mentation. According to whole-body dual-energy X-ray
      absorptiometry (DXA) results in the first and second year of the study, whole
      body mass, lean content, and mineral content, expressed as a percentage of whole
      body mass, stayed unchanged, while increase of fat content was significantly
      inhibited in group A, but not in group B, from the level in group C. As to the
      regional distribution of bone mineral content, the second year/first year value
      for head bone mineral content was significantly decreased with AAA
      supplementation compared with placebo, but no significant difference was found
      between CaCO(3) and placebo supplementation. Changes in mineral distribution in
      the arms, trunk, and legs showed no significant differences among the three
      groups. In addition to increasing BMD and preventing fracture, AAA Ca, but not
      CaCO(3), appears to inhibit the occurrence of spondylotic deformity and to
      decrease body fat content.

PMID- 14691685
TI  - Lack of association between vitamin D receptor gene polymorphism (BsmI) and
      osteomalacia.
AB  - Vitamin D receptor (VDR) gene polymorphism has been reported to be a determinant
      of bone formation and intestinal calcium absorption. We carried out this study to
      assess the role of VDR gene polymorphism in the pathogenesis of osteomalacia. We
      investigated BsmI polymorphisms in the gene encoding the 1,25 dihydroxyvitamin D
      receptor in 38 patients with osteomalacia and 31 healthy controls, along with
      examination of serum calcium, phosphorus, alkaline phosphatase, parathyroid
      hormone, and 25 hydroxyvitamin D levels. VDR allelic variants were: BB, 31.6%;
      Bb, 44.7%; and bb, 23.7% in the osteomalacia patients and BB, 19.4%; Bb, 61.3%;
      and bb, 19.4% in the controls. Although heterozygotes (Bb) were more frequent
      than other genotypes in both groups, the BB genotype was found to be more
      prevalent in osteomalacia than in controls. There was no statistical relationship
      between VDR genotype and osteomalacia. It is concluded that, in this small group
      of patients, there was no relationship between VDR allelic polymorphisms and
      osteomalacia.

PMID- 14691686
TI  - Bone loss in the contralateral asymptomatic hand in patients with complex
      regional pain syndrome type 1.
AB  - Regional osteoporosis was seen radiographically in clinically affected areas in
      patients with complex regional pain syndrome type 1 (CRPS1). The aim of the this
      study was to investigate whether bone loss developed in the contralateral hand in
      patients with unilateral CRPS1 of the hand. Thirty-two patients with CRPS1 of the
      hand were included in this study. Bone mineral density was measured in the left
      proximal femur and both ultradistal radiuses, using dual-energy X-ray
      absorptiometry. The subjects were classified as grades 1 to 3 according to the T
      score of both ultradistal radiuses (densitometric grades): grade 1, both radiuses
      were normal; grade 2, bone loss was determined only in the affected radius; and
      grade 3, there was bone loss in both radiuses. Twenty (62.5%) patients had bone
      loss in the affected hand; 11 patients (34.4%) had bone loss only on the affected
      side and 9 patients (28.1%) had bone loss on both sides. The mean duration of the
      period between the diagnosis of the injury and the measurement of bone density
      was 1.9 +/- 0.6 months in patients with grade 1, 3.1 +/- 1.0 months in patients
      with grade 2, and 5.5 +/- 2.2 months in patients with grade 3. The Spearman test
      showed a significant correlation between the period of injury and the
      densitometric grade ( R = 0.774; P = 0.0001). In conclusion, the current study of
      patients with CRPS1, showed that the bone loss in the asymptomatic contralateral
      hand developed at a later stage than that in the affected hand. This bone loss
      was less frequent and of a lower degree in the asymptomatic contralateral hand
      than in the affected hand. The bone loss in the asymptomatic contralateral hand
      could be explained by the loss of sympathetic tone in CRPS1 and contralateral
      sympathetic innervation.

PMID- 14691687
TI  - Bone mineral density in women with sarcoidosis.
AB  - Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Almost
      any organs of the body, but mostly the lungs, are involved. Bone mineral density
      (BMD) can be affected directly or indirectly in chronic granulomatous systemic
      diseases such as sarcoidosis. The aim of our study was to evaluate BMD in
      premenopausal and postmenopausal sarcoidosis patients with or without prednisone
      treatment and to compare their BMD values with those of a control group having
      the same menopausal status. Thirty-five premenopausal women (18 untreated, 8
      treated, and 9 controls) and 21 postmenopausal women (5 untreated, 5 treated, and
      11 controls) were included in the study. All of the patients had a histologically
      proven diagnosis and were being followed-up at the Sarcoidosis Outpatient Clinic
      of our unit. BMD of the lumbar (L) spine and femoral neck was measured by dual
      energy absorptiometry (DEXA). The subgroups of premenopausals and postmenopausals
      were compared separately. Comparison among the groups was performed by using
      analysis of variance. Age, duration of the disease, and body mass index were
      comparable in treated, untreated, and control subgroups of the pre- and
      postmenopausal groups, and the subgroups of postmenopausals had comparable
      durations since menopause. For premenopausals, BMD values at L1-4 were not
      significantly different among the subgroups (0.920 +/- 0.08 g/cm(2), 0.801 +/-
      0.09 g/cm(2), and 0.910 +/- 0.05 g/cm(2), for untreated, treated, and controls,
      respectively). However, the BMD value at the femoral neck in treated patients
      (0.921 +/- 0.1 g/cm(2)) was significantly lower than the values in untreated
      patients (1.080 +/- 0.2 g/cm(2); P < 0.01) and in controls (1.028 +/- 0.17
      g/cm(2); P < 0.05). For postmenopausals, the BMD value at L1-4 in controls (1.019
      +/- 0.07 g/cm(2)) was significantly higher than the values in untreated patients
      (0.783 +/- 0.01 g/cm(2)) and in treated patients (0.751 +/- 0.08 g/cm(2); P <
      0.001 for both). The BMD value at the femoral neck in controls (0.890 +/- 0.1
      g/cm(2)) was higher than the values in untreated patients (0.745 +/- 0.08
      g/cm(2)) and treated patients (0.747 +/- 0.1 g/cm(2)), but the difference was not
      statistically significant (P = 0.06). We concluded that sarcoidosis patients,
      especially postmenopausal patients with corticosteroid treatment, may have an
      increased risk of bone mineral loss. Large-scale studies are warranted in order
      to delineate the exact roles of the disease itself, menopausal status, and
      corticosteroid treatment in this bone mineral loss.

PMID- 14691688
TI  - Bone mass and metabolism in thalassemic children and adolescents treated with
      different iron-chelating drugs.
AB  - We evaluated bone mineral density (BMD) and bone turnover in 22 homozygous
      prepubertal beta-thalassemic patients treated with desferrioxamine. Ten patients
      underwent treatment with desferrioxamine for the whole study period, while 12
      patients stopped desferrioxamine and were then treated with deferiprone (L1).
      Lumbar and femoral BMD and bone metabolism markers were examined at baseline and
      after 1 and 3 years of follow up. All patients were prepubertal at baseline and
      they all became pubertal over the 3 years of follow up. At baseline, the mean
      lumbar Z score value was -2.048 SD +/- 0.75; the Z score was less than -2 SD in
      13 children, within -1 and -2 SD in 6, and within 0 and -1 SD in only 3 subjects.
      A significant BMD increase (P < 0.0001) was observed at both the lumbar
      (+8.466%/year) and the femoral level (average of +3.46%/year at neck and
      +5.83%/year at the intertrochanteric region) after 3 years, without any
      significant difference being shown between patients treated with desferrioxamine
      and those treated with L1. The mean Z score SD values increased to -1.957 +/-
      0.975 at 1 year (not significantly different from baseline) and to -1.864 +/-
      1.221 at 3 year follow up (P < 0.05 vs baseline); an increase in bone turnover
      was also observed. These findings show that low BMD, a hallmark of beta
      thalassemia, improves significantly when puberty begins; this increase involves
      different skeletal sites, regardless of pharmacological treatment with different
      iron-chelating drugs.

PMID- 14691689
TI  - Total lymphocyte count and femoral bone mineral density in postmenopausal women.
AB  - In vitro studies showed that several cytokines produced by the immune system can
      play a relevant role in modulating bone turnover, thus affecting the health of
      bone tissue. Our aim was to evaluate the association between total lymphocyte
      count (TLC) and femoral bone mineral density (BMD) in a sample of postmenopausal
      women. We studied 114 out of 124 consecutive, caucasian, home-dwelling,
      apparently healthy postmenopausal women referred for osteodensitometry by general
      practitioners. Femoral BMD was measured by dual-energy X-ray absorptiometry at
      five sites. A significant positive correlation (p < 0.001) was observed between
      TLC and BMD (T score) measured the five sites: total proximal femur ( r = 0.45),
      trochanter (r = 0.43), intertrochanteric region (r = 0.38), femoral neck (r =
      0.49), and Ward's triangle (r = 0.42). With a linear multiple regression model,
      TLC adjusted for age, weight, height, body mass index, and erythrocyte
      sedimentation rate showed a significant association with femoral BMD assessed at
      each of the five sites. The R(2) values ranged from 0.33 with BMD measured at
      Ward's triangle to 0.51 with BMD measured at the trochanter. The significance of
      the association between TLC and BMD ranged from P < 0.001 with BMD measured at
      the femoral neck to P < 0.05 with BMD measured at the intertrochanteric area. The
      results were similar when BMD was expressed as either a Z score (in the 110 of
      the 114 women aged 84 years or younger) or as absolute values. Our data show a
      positive association between TLC and femoral BMD in a sample of apparently
      healthy, postmenopausal women, supporting the view of a close connection between
      the immune system and bone tissue.

PMID- 14691690
TI  - Low calcium intake is associated with decreased adrenal androgens and reduced
      bone age in premenarcheal girls in the last pubertal stages.
AB  - In 50 premenarcheal girls selected from the lowest and highest end of the calcium
      intake distribution of a large population sample, we evaluated bone mineral
      density (BMD), together with the following hormonal-metabolic parameters:
      androstenedione (ASD), dehydroepiandrosterone (DHEA), dehydroepiandrosterone
      sulfate (DHEAS), testosterone (T), estradiol (E2), the apparent free fractions of
      T (AFTC) and E2 (AFEC), osteocalcin (OC), parathyroid hormone (PTH), and 25
      hydroxyvitamin D. Dietary calcium was assessed by 3-day food records, and BMD was
      measured at ultradistal (ud) and proximal (pr) radial sites, using dual-energy X
      ray absorptiometry. Calcium intake, which was below the recommended levels set
      for the Italian population and below the recommended daily allowance (RDA) in
      both subgroups of girls, did not show any apparent relationship with ud- and pr-
      BMD. However, despite the similar chronological age of the two premenarcheal
      groups, in the low-calcium consumers, we found lower bone age, delayed pubertal
      development, and lower circulating adrenal androgens. Of interest, in girls who
      had a low calcium intake, PTH levels were significantly higher. In all
      premenarcheals, we observed that DHEA, T, and AFTC were positively correlated
      with bone age and with bone density at both radial sites. Even though bone
      density at the two radial sites did not show any apparent relationship to calcium
      consumption, the increased mean PTH in the girls with low calcium intake seems to
      underscore the hormonal attempt in maintaining calcium homeostasis. In
      conclusion, low calcium intake and reduced levels of adrenal androgens, leading
      to decreased bone age and delayed pubertal development, indicate a link between
      calcium intake, the hormonal milieu, and skeletal maturation.

PMID- 14691691
TI  - Bone mineral density in elderly Chinese: effects of age, sex, weight, height, and
      body mass index.
AB  - To enhance our understanding of the relationship between bone mineral density
      (BMD) and sex, age, body mass index (BMI), weight, and height in elderly Chinese,
      we studied 258 males aged 50-80 years (mean +/- SD, 62.9 +/- 6.2 years) and 193
      females aged 46-75 years (59.0 +/- 6.2 years). We measured BMD at the lumbar
      spine (L1-L4), hip (femoral neck, trochanter, and intertrochanter), and Ward's
      triangle. A significant difference of age-adjusted BMD among male-female groups
      (P < 0.0001) was observed. After adjustment for weight, the magnitude of the sex
      difference in BMD was reduced at all studied skeletal sites; for example, the
      difference declined from 18.3% to 5.5% at the spine. There were significant
      differences in BMD among age-stratified groups at all the sites in both sexes (P
      < 0.01), except for spine BMD in males (P = 0.928). Regression analysis suggested
      that, with aging, greater differences of BMD distribution exist in elderly
      females than in males. Weight accounted for the greatest proportion of age
      adjusted BMD variation (e.g., at femoral neck, R(2) = 0.17 in males) among four
      variables: weight, height, BMI, and a principal component formed from weight and
      height. These results suggested that weight decreased the sex difference in BMD
      in elderly Chinese. Patterns of age-related BMD distribution and BMD change among
      different age groups differed between the sexes and between the studied sites.
      Weight accounted for most of the effect of two correlated variables (weight and
      height) on BMD in our sample.

PMID- 14691692
TI  - Acute effects of gentamicin on urinary electrolyte excretion in neonates.
AB  - It has recently been shown that a single dose of gentamicin causes immediate and
      transient calcium and magnesium renal wasting in adults. The aim of this study
      was to determine the acute effect of gentamicin administration on renal
      electrolyte handling in preterm and full-term neonates. Twenty-three neonates
      treated with gentamicin for suspected infection were enrolled in the study. Serum
      and 3-h urine electrolytes were measured before and immediately after gentamicin
      infusion on the 1st, 3rd, 4th, and 7th day of treatment. Serum gentamicin levels
      were monitored. Gentamicin caused a statistically significant post-infusion
      increase in fractional excretion of sodium and magnesium and in the urine calcium
      to urine creatinine ratio. Potassium and phosphate fractional excretion remained
      unchanged. The disturbances in electrolyte excretion were observed in full-term
      as well as in preterm neonates. Serum electrolyte levels remained unchanged. In
      conclusion, therapeutic doses of gentamicin result in urinary loss of sodium,
      calcium, and magnesium in neonates immediately after the infusion of the drug.
      These electrolyte changes may be of clinical importance, especially for sick
      preterm neonates.

PMID- 14691693
TI  - Does the learning phase influence the late outcome of patients with
      gastroesophageal reflux disease after laparoscopic fundoplication?
AB  - BACKGROUND: Although the degree of surgical experience clearly affects early
      outcome of laparoscopic antireflux surgery, its influence on long-term results
      has not been fully evaluated. The aim of this study was to verify whether the
      initial experience in laparoscopic antireflux surgery could also influence the
      late clinical outcome. METHODS: Clinical and endoscopic findings, together with
      quality of life, of the first 25 patients successfully submitted to laparoscopic
      fundoplication were compared with those of 25 matched controls operated on later.
      RESULTS: At more than 2 years', follow-up, reflux symptoms, endoscopic findings,
      use of antisecretory drugs, side effects, and quality of life were not
      significantly different in both groups, despite a high occurrence of major
      anatomical failures (three vs one) in the first set of patients. CONCLUSION: The
      late clinical outcome of patients with gastroesophageal disease operated on
      during the learning phase or after gaining experience is not different, provided
      the surgeon is adequately trained in laparoscopic surgery.

PMID- 14691694
TI  - Pneumoperitoneum impairs blood flow and augments tumor growth in the abdominal
      wall.
AB  - BACKGROUND: Despite several clinical and experimental studies, the mechanisms
      behind the development of port site metastases in laparoscopic surgery have
      remained largely unknown. The current study was designed to investigate the
      effect of pneumoperitoneum on blood flow in the abdominal wall and its possible
      effects on tumor growth at this site. METHODS: A total of 40 Wistar Fu rats had a
      laser Doppler probe placed on their left rectus muscle and a suspension of 50,000
      adenocarcinoma cells was injected into their right rectus muscle. The
      experimental group (n = 20) was insufflated with air at 10 mmHg for 45 min while
      abdominal blood flow was registered before and during insufflation and after
      exsufflation. The control group (n = 20) was not insufflated but the blood flow
      was recorded in the same manner. After 9 days, all animals were killed and the
      occurrence of tumor was observed. The tumors were analyzed with respect to weight
      and volume. RESULTS: The insufflation caused an 82% reduction in blood flow in
      the experimental group (p < 0.001). No reduction in blood flow was registered in
      the control group. Tumor nodules developed significantly more often in the
      insufflated group (20/20) compared to the controls (14/20) (p = 0.016). Tumor
      weight (p = 0.003) and volume (p < 0.001) were significantly increased in the
      insufflated group. CONCLUSIONS: Pneumoperitoneum seems to enhance tumor growth.
      It also causes a significant reduction in blood flow in the abdominal wall, which
      may contribute to the increased susceptibility of tumor take.

PMID- 14691695
TI  - Experience with the use of tissue adhesives in pediatric endoscopic surgery.
AB  - BACKGROUND: Due to technological improvements, the use of tissue adhesives and
      glues for tissue approximation and hemostasis in surgery has increased. We report
      our preliminary experience with this technology in pediatric endosurgery.
      METHODS: Between 1997 and 2000, we employed tissue adhesives in 48 pediatric
      patients during laparoscopic procedures. In 25 patients, the glue was adopted for
      the hemostasis of parenchimal organs (liver in 24 cases and spleen in one). In
      three cases, the glue was used to repair organ perforation, in 19 it was used to
      close the distal part of a patent processus vaginalis in case of congenital
      inguinal hernia. In the final case, the glue was adopted to achieve optimal
      airtightness in case of pulmonary biopsy. The glue was injected with the aid of a
      needle positioned transparietally. RESULTS: The procedure was easy and rapid in
      all cases, and there were no problems or complications related to glue
      positioning at a mean follow up of 51 months. CONCLUSION: Tissue adhesives are a
      very versatile product for use in pediatric laparoscopic surgery. It is likely
      that their usage will increase as the technology improves and more effective
      products are developed.

PMID- 14691696
TI  - Laparoscopic versus open appendectomy: what is the real difference? Results of a
      prospective randomized double-blinded trial.
AB  - BACKGROUND: The comparison of laparoscopic to open appendectomy has been reviewed
      in many retrospective and prospective studies. Some report shorter hospital
      stays, less postoperative pain, and earlier return to work while others fail to
      demonstrate such differences. We performed a prospective, randomized double
      blinded trial to evaluate this ongoing debate. METHODS: Fifty-two consecutive men
      presenting with signs and symptoms suggestive of acute appendicitis were
      randomized to undergo either laparoscopic appendectomy or open appendectomy.
      Length of operative times, hospital stay, lost work days, visual analog pain
      scores, and operative costs were compared. RESULTS: Length of stay averaged 21.5
      h for the laparoscopic group and was not statistically different when compared to
      the open group. Perceived postoperative pain on postoperative days 1 and 7 were
      not statistically different between the two groups. Mean time to return to work
      was 11 days, and there was no statistical difference between groups. Operative
      costs were >600 dollars greater for the laparoscopic approach. CONCLUSIONS: In
      this prospective randomized double-blinded trial, laparoscopic appendectomy
      appears to confer no significant advantage over open appendectomy for
      postoperative pain or lost work days. It does carry an increase in operating room
      costs and, contrary to other reports, hospital stay is not shortened. Further
      studies are needed to determine if specific populations, such as the obese or
      women, may benefit from a minimally invasive approach to appendicitis.

PMID- 14691697
TI  - Experience with over 3,000 open and laparoscopic bariatric procedures:
      multivariate analysis of factors related to leak and resultant mortality.
AB  - BACKGROUND: Intestinal leak is a potentially lethal complication of Roux en-Y
      gastric bypass (GBP). Identification of patients at high risk for leak may reduce
      complication rates of surgeons early in the procedure learning curve. METHODS: A
      total of 3073 patients who underwent GBP were analyzed using univariate and
      multivariate logistic regression analyses of the following preoperative factors:
      hypertension (HTN), diabetes mellitus (DM), sleep apnea (SA), age, gender,
      weight, body mass index (BMI), and surgery type. Multivariate logistic regression
      analysis was performed for each procedure type. RESULTS: There were 48 (1.5%)
      deaths. Independent risk factors for death included leak, weight, procedure type,
      and HTN. A total of 102 (3.2%) leaks were found. Independent factors for leak
      included age, male gender, SA, and procedure type. CONCLUSION: The data suggests
      that older, heavier male patients with multiple comorbid conditions are at
      increased risk for leak and mortality. Surgeons early in their learning curve
      should avoid these high-risk patients to reduce complications.

PMID- 14691698
TI  - Comparative results of endoluminal gastroplasty and laparoscopic antireflux
      surgery for the treatment of GERD.
AB  - BACKGROUND: Transoral endoluminal gastroplasty (EG) by the Bard Endocinch device
      is available for the treatment of gastroesophageal reflux disease (GERD). This
      study assessed the early (<or=12 months) outcomes in patients undergoing EG
      performed by one gastroenterologist compared with another set of patients
      referred by the same gastroenterologist for laparoscopic antireflux surgery (LAS)
      at a foregut surgery center. METHODS: From June 2000 to July 2002, 87 consecutive
      patients cared for by a single gastroenterologist were diagnosed with refractory
      GERD and underwent either EG (n = 47) or referral for LAS (n = 40). Preoperative
      evaluation included symptom assessment, pH studies, and motility studies.
      Outcomes were assessed by symptomatic improvement and dependence on anti-acid
      medications. Data analyzed by chi-square or Mann-Whitney tests are reported as
      mean +/- SEM. RESULTS: Preoperative symptom duration, Johnson-DeMeester (JD)
      score, % time pH < 4, and reflux episodes were statistically similar in both
      treatment groups. The follow-up times for EG and LAS groups were 7.3 +/- 0.9 and
      8 +/- 0.4 months, respectively. Of EG patients, 94% were available for follow-up,
      and all LAS patients had follow-up data. Overall, 66% of patients were satisfied
      with EG as compared to 93% after LAS (p = 0.1). Postoperative PPI/motility agent
      use was 32% for EG and 13% for LAS (p = 0.03). Identifiable causes of EG failure
      were premature procedure termination due to hypoxia or bleeding (three patients),
      intractable vomiting (two patients), and delayed gastric emptying (five
      patients). Three EG patients subsequently had LAS within 6 months of the
      procedure. CONCLUSIONS: LAS offers greater reduction in medication use than EG,
      as well as more durable patient satisfaction. Benefits of EG may include short
      term symptomatic improvement while considering definitive surgical management.

PMID- 14691699
TI  - Laparoscopic splenectomy for lymphoproliferative disease.
AB  - BACKGROUND: Elective laparoscopic splenectomy (LS) achieves excellent results for
      benign hematologic diseases. The role of LS for hematologic malignancies is
      harder to define owing to associated splenomegaly and patient disease that may
      alter outcome. METHODS: Retrospective review of single institution experience
      1996 through 2002. To limit variability of disease processes, only patients with
      immune thrombocytopenic purpura (ITP) and lymphoproliferative disease (LPD) were
      studied. RESULTS: A total of 211 LS have been performed, including 73 for LPD and
      86 for ITP. Patients with LPD were significantly older, 61 vs 46 years p<0.001;
      male, 45 (62%) vs 33 (38%), p<0.001; and larger splenic weight, 680 vs 162 g,
      p<0.001. Fifty-nine patients (81%) with LPD were operated with standard LS with a
      conversion rate of 15%. Hand-assisted LS was performed in 14 patients (19%), and
      three were converted to open. Compared to ITP, patients with LPD had longer
      operative time, 148 vs 126 min, p<0001, and higher blood loss, 200 vs 100 cc, p =
      0.004. There was one mortality (0.6%), and morbidity occurred in six patients
      (8%) with LPD and seven (8%) with ITP. The median length of stay was 3 days for
      LPD and 2 days for ITP, p = 0.03. Forty-six patients were principally operated
      for a diagnosis, and 27 (60%) were found to have lymphoma. CONCLUSIONS: LS can be
      performed safely in patients with LPD, and when used judiciously with hand
      assisted techniques can be performed with low conversion and morbidity rates.
      Splenectomy plays an important role in establishing the diagnosis of lymphoma in
      LPD.

PMID- 14691700
TI  - Repair of ventral hernias in morbidly obese patients undergoing laparoscopic
      gastric bypass should not be deferred.
AB  - BACKGROUND: There is no consensus regarding the optimal treatment of ventral
      hernias in patients who present for weight loss surgery. METHODS: Medical records
      of consecutive morbidly obese patients who underwent laparoscopic Roux-en-Y
      (LRYGB) gastric bypass with a secondary diagnosis of ventral hernia were
      reviewed. Only patients who were beyond 6 months of follow-up were included.
      RESULTS: The study population was 85 patients. There were three groups of
      patients according to the method of repair: primary repair (59), small intestine
      submucosa (SIS) (12), and deferred treatment (14). Average follow-up was 26
      months. There was a 22% recurrence in the primary repair group. There were no
      recurrences in the SIS group. Five of the patients in the deferred treatment
      group (37.5%) presented with small bowel obstruction due to incarceration.
      CONCLUSION: Biomaterial mesh (SIS) repair of ventral hernias concomitant with
      LRYGB resulted in the most favorable outcome albeit having short follow-up.
      Concomitant primary repair is associated with a high rate of recurrence. All
      incarcerated ventral hernias should be repaired concomitant with LRYGB, as
      deferment may result in small bowel obstruction.

PMID- 14691701
TI  - The effects of staging laparoscopy on trocar site and peritoneal recurrence of
      pancreatic cancer.
AB  - BACKGROUND: Staging laparoscopy (SL) has been used to assess resectability of
      patients with pancreatic cancer. It has lead to increased resectability rates and
      decreased morbidity. However, experimental data suggests that laparoscopy and
      peritoneal insufflation can promote tumor growth and potential recurrence. Few
      clinical data exist to allow assessment of whether these theoretical concerns
      translate into clinical problems. The purpose of this study was to determine if
      SL increases the incidence of trocar-site and peritoneal recurrence of pancreatic
      cancer. METHODS: A retrospective review of all patients evaluated for pancreatic
      cancer from 1996 to 2001, inclusive, was included in this study. Patients were
      divided into five groups: nonoperative management (NM), SL followed by resection
      (SL-R), SL without resection (SL-NR), exploratory laparotomy with resection (EL
      R), and exploratory laparotomy without resection (EL-NR). Patient records were
      assessed for postoperative occurrence of carcinomatosis and/or malignant ascites,
      trocar- or incisional-site recurrence, use of postoperative chemotherapy or
      radiation therapy, and survival. RESULTS: A total of 235 patients were included.
      Peritoneal progression of disease: NM 15.9%, SL 24.2%, EL 31.6% ( p = 0.03).
      Trocar/incisional recurrence: SL 3.0%, EL 3.9% ( p = NS). Use of
      chemotherapy/radiotherapy: NM 29.4%, SL-R 76.5%, SL-NR 62.5%, EL-R 69.6%, EL-NR
      41.5%. Median survival (months): NM 3; SL-R 15, EL-R 10 ( p = NS); SL-NR 6, EL-NR
      5 ( p = NS). CONCLUSION: SL does not increase the occurrence of trocar-site
      disease or peritoneal disease progression of pancreatic cancer. Patients who are
      found not to be resectable by SL are more likely to receive postoperative
      treatment. However, this does not appear to affect survival greatly.
      Nevertheless, avoidance of nontherapeutic laparotomy is worthwhile in these
      patients.

PMID- 14691702
TI  - Laparoscopic treatment of enteric fistulas.
AB  - BACKGROUND: Elective laparoscopically assisted sigmoid colectomy for diverticular
      disease and ileocolic resection for terminal ileal Crohn's disease are safe and
      beneficial procedures in many patients. However, few data exist regarding the
      laparoscopic management of enteric fistulas from diverticular and Crohn's
      disease. METHODS: We completed a retrospective chart review of patients who
      underwent laparoscopic treatment of enteric fistulas complicating diverticular
      and Crohn's disease. RESULTS: During an 8-year period (1994-2002), 72 patients
      underwent 73 laparoscopically assisted bowel resections for enteric fistulas by
      one surgeon at the Mount Sinai Medical Center. Ninety percent of patients had
      Crohn's disease, the average age was 39, and the male/female ratio was 38/34.
      Patients had a history of prior abdominal surgery in 39.7% of cases. Multiple
      fistulas were present in 30% of patients and 12.3% underwent multiple resections
      at the time of operation. Mean operating time was 199 min, and the conversion
      rate was 4.1%. Average length of stay was 5.2 days. There were no mortalities in
      the series. Overall morbidity was 11%. CONCLUSIONS: Laparoscopic management of
      enteric fistula disease is safe and effective. Low morbidity and short hospital
      stay demonstrate the safety and benefit of the minimally invasive approach for
      even complicated fistula disease in patients with history of prior abdominal
      surgery and multiple fistulas, or in patients requiring multiple resections for
      fistulas from diverticular and Crohn's disease.

PMID- 14691703
TI  - The Lap-Band system in the United States: one surgeon's experience with 271
      patients.
AB  - BACKGROUND: The LAP-BAND system is considered an important bariatric surgery
      procedure in many countries and is rapidly gaining acceptance in the United
      States. Outcomes data emerging in the United States parallel European and
      Australian experience. The purpose of this study was to examine our experience
      with this procedure in the United States. METHODS: Between November 2000 and
      September 2002, 271 patients (236 women) underwent LAP-BAND system placement. The
      mean age of patients was 40 years (18-63); preoperative mean body weight was 125
      kg (93-192). Surgeries were performed using either the two-step (pars flaccida to
      perigastric) or the pars flaccida technique with three (1.1%) conversions to open
      procedures. Mean operative time was 42 min (23-86); average hospital stay was 1
      day (4 h to 7 days). RESULTS: The mean body mass index (BMI) decreased from a
      baseline of 45.3 kg/m(2) (35-68) to 41.9 ( n = 178), 39.5 ( n = 101), 38.4 (n =
      81), 36.5 (n = 72), 35.9 (n = 51), and 35.1 (n = 21) kg/m(2) at 3, 6, 9, 12, 18,
      and 24 months, respectively, after surgery. Mean excess weight loss was 40% at 12
      months and 43% at 24 months. As patients lost weight, comorbid conditions
      improved. No deaths occurred, no bands had to be removed, and postoperative
      complications were minor: 20 (7.3%) access port problems, 18 (6.6%) gastric pouch
      dilatations, five (1.8%) gastric slippages, and five (1.8%) stoma obstructions.
      All were managed conservatively or repaired laparoscopically using the original
      bands. Additional complications included four cases of pneumonia and one case of
      pulmonary embolism. One patient required reoperation because of trocar site
      bleeding. CONCLUSIONS: The LAP-BAND system is a safe and effective bariatric
      procedure leading to considerable weight loss and reduction in comorbidity.

PMID- 14691704
TI  - Current status of laparoscopic gastrectomy for cancer in Japan.
AB  - Because of the increased incidence of early gastric cancer in Japan, minimally
      invasive laparoscopic approaches to gastric malignancies have been under
      development since 1991. Laparoscopic local resection of the stomach, i.e.,
      laparoscopic wedge resection (LWR) and intragastric mucosal resection (IGMR), is
      used to treat mucosal cancer without lymph node metastasis. Laparoscopy-assisted
      distal gastrectomy (LADG) is used to treat early gastric cancer with risk factors
      for regional lymph node metastasis. A survey conducted by the Japan Society for
      Endoscopic Surgery showed that 1428 LWRs, 260 IGMRs, and 2600 LADGs were
      performed between 1991 and 2001 in departments of endoscopic surgery in Japan.
      Laparoscopic gastrectomy for gastric cancer is still under development in Japan.
      According to short-term results reported by a small group of surgeons,
      laparoscopic approaches to gastric cancer provide for minimal invasion, early
      recovery, and decreased morbidity and mortality. If the advantages can be
      confirmed in one or more multicenter randomized control studies of the long-term
      outcome of patients undergoing laparoscopic gastrectomy for gastric cancer, the
      procedure should come into wide acceptance and use.

PMID- 14691706
TI  - Laparoscopy for appendicitis and cholelithiasis during pregnancy: a new standard
      of care.
AB  - BACKGROUND: Subsequent to a report from the authors' institution, the
      laparoscopic management of symptomatic cholelithiasis and appendicitis during
      pregnancy has become the standard of care at LDS Hospital using institutional
      guidelines. For comparison with previous outcomes described by the authors, 59
      additional laparoscopic cases are reported. METHODS: Medical records of all
      pregnant patients at LDS Hospital who underwent open or laparoscopic
      cholecystectomy or appendectomy between 1998 and 2002 were reviewed. The outcomes
      were compared with the authors' previous data. RESULTS: The laparoscopic
      management of symptomatic cholelithiasis and appendicitis during pregnancy
      increased from 54% to 97%. No significant differences in preterm delivery rates,
      birth weights, or 5-min Apgar scores were found between the two periods. No birth
      defects or uterine injuries occurred. CONCLUSIONS: With the use of the authors'
      guidelines, laparoscopy has become the standard of care for managing symptomatic
      cholelithiasis and appendicitis during pregnancy at LDS Hospital without
      significant increase in morbidity or mortality.

PMID- 14691705
TI  - Bile duct injuries during laparoscopic cholecystectomy: a 1994-2001 audit on
      13,718 operations in the area of Rome.
AB  - BACKGROUND: Bile duct injuries (BDIs) during laparoscopic cholecystectomy (LC)
      still are reported with greater frequency than during open cholecystectomy (OC).
      METHODS: In 1999, a retrospective study evaluating the incidence of BDIs during
      LC in the area of Rome from 1994 to 1998 (group A) was performed. In addition, a
      prospective audit was started, ending in December 2001 (group B). RESULTS: In
      group A, 6,419 LCs were performed (222 were converted to OC; 3.4%). In group B,
      7,299 LCs were performed (225 were converted to OC; 3.1%). Seventeen BDIs (0.26%)
      occurred in group A and 16 (0.22%) in group B. Overall, mortality and major
      morbidity rates were 12.1% and 30.3%, respectively, without significant
      differences between the two groups. CONCLUSIONS: The incidence and clinical
      relevance of BDIs during LC in the area of Rome appeared to be stable over the
      past 8 years and were not influenced by the use of a prospective audit, as
      compared with a retrospective survey.

PMID- 14691707
TI  - Laparoscopic vs open resection for the treatment of diverticular disease.
AB  - INTRODUCTION: The aim of this study was to evaluate whether laparoscopic colon
      resection (LCR) offers any advantages over open colon resection (OCR) in the
      treatment of diverticular disease. METHODS: Between 1992 and 2002, 95 patients
      underwent LCR and 80 patients underwent OCR for the treatment of diverticular
      disease. Demographics, details of operative procedure, outcome, and pathology
      were compared. RESULTS: Patients in both groups were matched for age, sex, body
      mass index, history of previous abdominal operations, comorbidities, location of
      the disease, and presence of complications. LCR resulted in significantly less
      estimated blood loss and postoperative complications, shorter time to first bowel
      movement, and shorter length of stay than the OCR. There was no difference in
      operative time, intraoperative complications, mortality rates between groups.
      CONCLUSIONS: LCR is a safe and effective approach for the treatment of patients
      with diverticular disease. It results in less estimated blood loss, shorter time
      to first bowel movement, less postoperative complications, and shorter length of
      hospital stay.

PMID- 14691708
TI  - Validity and reliability of a virtual reality upper gastrointestinal simulator
      and cross validation using structured assessment of individual performance with
      video playback.
AB  - BACKGROUND: This study aims to evaluate the ability of an upper gastrointestinal
      virtual reality simulator to assess skills in endoscopy, and to validate its
      metrics using a video-endoscopic (VES) technique. METHODS: The 32 participants in
      this study were requested to undertake two cases on the simulator (Simbionix,
      Israel). Each module was repeated twice. The simulator's metrics of performance
      were used for analysis. two blinded observers rated performance watching the
      simulator's playback feature. RESULTS: There were 11 novices (group 1), 11
      trainees with intermediate experience (10-50 procedures, group 2), and 10
      experienced endoscopists (>200 procedures, group 3). There was a significant
      difference in the total time required to perform the procedure (p < 0.001),
      percentage of mucosa visualized (p < 0.001), percentage of pathologies visualized
      (p < 0.001), and number of inappropriate retroflexions (p = 0.015) across the
      three groups. The reliability of assessment on the simulator was greater than
      0.80 for all parameters. The VES assessment also was able to discriminate
      performance across the groups (p < 0.001). There was a significant correlation
      between the VES score and the percentage of mucosa visualized (rho = 0.60; p <
      0.001). CONCLUSIONS: The upper gastrointestinal simulator may be a useful tool
      for determining whether a trainee has achieved a desired level of competence in
      endoscopy. The next step will be to validate the VES score in real procedures.

PMID- 14691709
TI  - Open and laparoscopic appendectomy are equally safe and acceptable in children.
AB  - BACKGROUND: The aim of this study was to evaluate prospectively whether
      laparoscopic (LA) and open appendectomy (OA) are equally safe and feasible in the
      treatment of pediatric appendicitis. METHODS: A total of 517 children with acute
      appendicitis were randomly assigned to undergo LA or OA appendectomy, based on
      the schedule of the attending surgeon on call. Patient age, sex, postoperative
      diagnosis, operating time, level of training of surgical resident, length of
      postoperative hospitalization, and minor and major postoperative complications
      were recorded. Chi-square analysis and the Student t-test were used for
      statistical analysis. RESULTS: In all, 376 OA and 141 LA were performed. The two
      groups were comparable in terms of patient demographics and the incidence of
      perforated appendicitis. The operative time was also similar (47.3 +/- 19.7 vs
      49.9 +/- 12.9 min). The overall incidence of minor or major complications was
      11.2% in the OA group and 9.9% in the LA group. CONCLUSION: Pediatric patients
      with appendicitis can safely be offered laparoscopic appendectomy without
      incurring a greater risk for complications. Nevertheless, a higher (but not
      significantly higher) abscess rate was found in patients with perforated
      appendicitis who underwent laparoscopy.

PMID- 14691710
TI  - Protection of trocar sites from gallbladder cancer implantation by sodium
      hyaluronate carboxymethylcellulose-based bioresorbable membrane (Seprafilm) in a
      murine model [corrected].
AB  - BACKGROUND: The risk of port site metastasis in laparoscopic surgery for cancer
      patients is a problem that has yet to be resolved. We examined the protective
      effect of a sodium hyaluronate-based bioresorbable membrane (Seprafilm) on tumor
      cell implantation at laparoscopic trocar sites. METHODS: Four 2-mm trocar sites
      were created in nude mice, and the peritoneal wounds were covered with different
      sized pieces of Seprafilm. The protective effect of Seprafilm on the implantation
      of GB-d1 (a human gallbladder cancer cell line) at the trocar sites was assessed
      after 7 days. In addition, the effects of sodium hyaluronate and Seprafilm on the
      growth and motility of GB-d1 were examined in vitro. RESULTS: Seprafilm
      significantly decreased the incidence of implantation compared with the control
      group. Histologically, Seprafilm was observed on days 1 and 3, as a sheet of gel
      that covered the injured peritoneum and muscle layer. In an invasion assay using
      Seprafilm, no cells were found to infiltrate through the gel sheet. CONCLUSION:
      Seprafilm protects peritoneal wounds by physically covering the injured
      peritoneum. Therefore, if Seprafilm were attached to the injured peritoneum after
      laparoscopic surgery for cancer patients, it might reduce port site metastasis.

PMID- 14691711
TI  - In vivo studies comparing the biocompatibility of various polypropylene meshes
      and their handling properties during endoscopic total extraperitoneal (TEP)
      patchplasty: an experimental study in pigs.
AB  - BACKGROUND: Polypropylene (PP) meshes are currently being used in millions of
      operations for hernial repair. We tested several recently modified PP meshes to
      evaluate them in terms of their biocompatibility and handling characteristics
      during minimally invasive procedures. METHODS: Four different PP meshes (a
      heavyweight PP, Atrium; a lightweight PP incorporating absorbable polyglactic
      acid, Vypro II; a lightweight PP, Parietene; and a titanium-coated lightweight
      PP, Ti-Mesh Extralight), all implanted using the endoscopic total
      extrapreperitoneal (TEP) technique, were investigated in groups comprising 11
      pigs each. After 94 +/- 5 days, the animals were autopsied and tissue samples
      were studied histologically, immunohistochemically, and electron-microscopically.
      RESULTS: Whereas endoscopic handling of the Vypro II mesh proved difficult, the
      already good properties of the Atrium mesh were significantly improved on by
      Parietene and the Ti-Mesh. Clear differences were also found in the shrinkage
      characteristics of the implant materials. In comparison with Atrium (12%), Vypro
      II mesh shrinkage was significantly greater (28%), whereas Parietene (7%) and Ti
      Mesh (5%) incurred less shrinkage. With regard to the chronic inflammatory
      reaction, the titanium-coated mesh showed a significantly lower inflammatory
      activity (13.1% partial volume [%PV] vs 34.1%PV and 29.0%PV) than the lightweight
      meshes Vypro II and Parietene, but-with the exception of the monocytic (0.2 vs
      9.1, 5.1, and 7.9) and B-lymphocytic reaction (1.1 vs 18.0, 11.7, and 12.2)-no
      significant difference was seen in comparison with Atrium. The various mediators
      in the extracellular matrix (matrix metalloproteinases 1 [MMP-1 transforming
      growth factor beta [TGF-beta], urokinase plasminogen activator [uPA], and type I
      collagen) tended to show the highest expression with Vypro II (13.6, 113.2,
      132.7, and 139.5, respectively) and the lowest expression with Ti-Mesh (11.9,
      68.5, 92.8, and 75.0, respectively). With regard to cell proliferation, Parietene
      and Ti-Mesh appeared to have slight advantages, but no differences were observed
      in the apoptotic rate. CONCLUSION: In our opinion, despite a reduction in
      material, Vipro II, on account of the inflammatory reaction, does not represent a
      true improvement over the meshes currently used for hernia repair. In comparison,
      the two lightweight PP patches are characterized by a more favorable foreign body
      reaction, with the titanium coating of the Ti-Mesh providing an additional
      advantage in terms of its biocompatibility.

PMID- 14691712
TI  - Laparoscopic gastric bypass after failed open horizontal stapled gastroplasty.
AB  - The number of people in the population who have undergone an operative procedure
      for morbid obesity is likely to rise steadily as the awareness and popularity of
      bariatric surgery continues to develop. As this number increases, the number of
      patients with long-term failures and complications from these procedures will
      also rise. Although previous operations, particularly open procedures, normally
      deter surgeons from choosing a laparoscopic approach, the evolving technical
      skill of laparoscopic surgeons should allow for the reconsideration of these
      inhibitions. In this case, we present of laparoscopic Roux-en-Y gastric bypass on
      a 48-year-old woman who had undergone horizontal gastric stapling 20 years prior
      to presentation.

PMID- 14691713
TI  - Synchronous bilateral endoscopic adrenalectomy: experiences after 18 operations.
AB  - BACKGROUND: Patients who undergo unilateral adrenalectomy are known to benefit
      from the endoscopic procedure. Only a few reports on bilateral endoscopic
      adrenalectomy exist. The optimal approach and the value of this operation were
      assessed in this study. METHODS: For 18 patients, synchronous bilateral lateral
      adrenalectomy with intraoperative repositioning was performed for different
      indications. The transperitoneal and retroperitoneal approaches were varied on
      both sides. RESULTS: With the reported procedure, the operative time diminished
      considerably. Blood loss was low, and no blood transfusions were required. No
      conversion to an open procedure was necessary. There were no intraoperative or
      postoperative complications, except for one death from pulmonary embolism. The
      mean postoperative hospital stay was 7 days, and the follow-up evaluation showed
      overall improvement. CONCLUSION: The risk associated with endoscopic bilateral
      adrenalectomy is low. Transperitoneal and retroperitoneal lateral adrenalectomy
      are recommended as approaches of choice. The authors advocate early bilateral
      adrenalectomy for Cushing's disease after unsuccessful transsphenoidal operation
      and ectopic adrenocorticotropic hormone production from an inaccessible tumour.

PMID- 14691714
TI  - Toward totally endoscopic coronary artery surgery.
AB  - BACKGROUND: Here we explore a method of using robotics to reduce morbidity and
      mortality in conventional coronary surgery. METHODS: Using a robotic surgical
      system two surgeons completed five steps: (1) 80 synthetic suture exercises; (2)
      76 left internal thoracic artery to left anterior descending (LIMA-to-LAD) on
      porcine hearts; (3) cadaveric port placement for assessing optimal access; (4)
      endoscopic stabilization in the live porcine model; and, finally (5) eight
      clinical LIMA-to-LADs performed robotically. RESULTS: After 70 hours training,
      mean dry lab times fell from 7.0 and 5.8 min to 5.7 and 5.1 min in the two
      surgeonstab series. Wet lab times fell from 40.1 and 28.5 min to 28.8 and 19.2
      min. In the clinical series of eight patients there were no mortalities; all had
      uncomplicated postoperative recovery and all were angina free at 6-week follow
      up. CONCLUSION: The learning curve for robotic training is short, and
      reproducible results can be achieved clinically, after appropriate training,
      resulting in real patient benefit.

PMID- 14691715
TI  - Determinants of competency judgments by experienced laparoscopic surgeons.
AB  - BACKGROUND: The definitive criteria for assessing competence remain elusive. In
      our study, we aimed to identify the determinants of competence assessment used by
      individual laparoscopic surgeons. METHODS: In a blinded fashion, five
      laparoscopic surgeons rated 27 subjects on three laparoscopic simulations in four
      skill categories: clinical judgment, dexterity, serial/simultaneous complexity,
      and spatial orientation. The raters then assessed overall subject competence for
      each procedure. Point-biserial correlational analyses and cluster analyses were
      performed to ascertain the relationships among the various scales. RESULTS: All
      of the correlations between the skills' ratings and competence judgments were
      statistically significant ( p <.05). No skill rating was consistently more highly
      correlated with the competence rating. There were no distinct patterns of
      correlations for each rater or each procedure. One factor emerged from each
      cluster analysis of the skills measures. CONCLUSIONS: The results suggest that
      the four skills scored in the study are highly correlated with each other and are
      important in determining competence. The cluster analyses revealed that the
      surgeon raters shared a common perception of competence.

PMID- 14691716
TI  - Laparoscopic total mesorectal excision (TME) for rectal cancer surgery: long-term
      outcomes.
AB  - BACKGROUND: Total mesorectal excision (TME) offers the lowest reported rates of
      local recurrence and the best survival results in patients with rectal cancer.
      However, the laparoscopic approach to resection for colorectal cancer remains
      controversial due to fears that oncologic principles will be compromised. We
      assessed the feasibility, safety and long-term outcome of laparoscopic rectal
      cancer resections following the principles of TME. The aim of this study was to
      evaluate the perioperative outcome and long-term results of laparoscopic TME.
      METHODS: We reviewed the prospective database of 102 consecutive unselected
      patients undergoing laparoscopic TME for rectal cancer between November 1991 and
      December 2000. Follow-up was done through office charts or direct patient
      contact. Recurrence and survival curves were generated by the Kaplan-Meier
      method. RESULTS: Laparoscopic TME was completed successfully in 99 patients,
      whereas conversion to an open approach was required in three cases (3%). The
      overall morbidity and mortality rates were 27% and 2%, respectively, with an
      overall anastomotic leak rate of 17%. Of the 102 patients, four were excluded
      from the oncologic evaluation because final pathology was not confirmatory (two
      had anal canal squamous cell carcinoma and two had villous adenoma with
      dysplasia). In 90 of the 98 remaining patients (91.8%), the resection was
      considered curative. The remainder had a palliative resection due to synchronous
      metastatic disease or locally advanced disease. Mean follow-up was 36 months
      (range, 6-96). There were no trocar site recurrences. The local recurrence rate
      was 6%, and the cancer-specific survival of all curatively resected patients was
      75% at 5 years. The overall survival rate of all curatively resected patients was
      65% at 5 years; mean survival time was 6.23 years (95% confidence interval [CI],
      5.39-7.07). CONCLUSION: Laparoscopic TME is feasible and safe. The laparoscopic
      approach to the surgical treatment of operable rectal cancer does not seem to
      entail any oncologic disadvantages.

PMID- 14691718
TI  - The outcome of childhood obesity management depends highly upon patient
      compliance.
AB  - Over the last 20 years, obesity in childhood and adolescence has become a major
      public health concern due to dramatically increasing prevalence rates. We
      evaluated the outcome of 294 children (135 girls, 159 boys) aged 6-16 years
      (median 10.9 years) enrolled in a single centre outpatient obesity intervention
      programme consisting of periodical visits to the outpatient unit with regular
      medical and dietetic counselling aiming at a modification of dietary and activity
      patterns of patients and parents. The average number of visits to the outpatient
      unit was 3.6 (SD 2.7) with a mean visit interval of 62.1 days. A mean drop-out
      rate of 27.5% between each scheduled appointment occurred. In a stepwise
      regression model, neither reduction of the standard deviation score of patients'
      body mass index (BMI-SDS) nor dietary counselling contributed to the total number
      of visits. The only significant contributor was the patients' initial BMI-SDS
      explaining 4.6% of the variance of attended visits adjusted for age and sex.
      Segregation of the patients into an "obesity" (initial BMI-SDS >/=90th
      percentile, at least three visits attended, n=59) and an "excessive obesity"
      (initial BMI-SDS >/=99th percentile, at least four visits attended, n=75)
      subgroup showed a mean reduction of BMI-SDS in the "obesity" group at visit three
      of 0.14 (SD 0.21, P<0.0001), and in the "excessive obese" group at visit four of
      0.17 (SD 0.22, P<0.001). In a stepwise regression model, the mean interval
      between visits and regular dietary counselling explained 11.7% of the variance of
      BMI-SDS reduction at visit three in both subgroups. CONCLUSION: there is an
      urgent need for efficient strategies to improve adherence of outpatients to
      obesity treatment since, in terms of reduction in body mass index standard
      deviation score, a beneficial outcome can be achieved for compliant obese
      children and adolescents.

PMID- 14691717
TI  - Sulindac sulfide and caffeic acid phenethyl ester suppress the motility of lung
      adenocarcinoma cells promoted by transforming growth factor-beta through Akt
      inhibition.
AB  - Cell migration is essential for invasive and metastatic phenotypes of cancer
      cells. Potential chemopreventive agents of cancer-sulindac sulfide, caffeic acid
      phenethyl ester (CAPE), curcumin, and (+)-catechin-have been reported to
      interfere with several types of intracellular signaling. In this study, we
      examined the effects of these agents on transforming growth factor-beta(TGF-beta)
      induced motility and Akt phosphorylation in A549 cells. Judged by gold particle
      phagokinesis assay, sulindac sulfide, CAPE, and curcumin suppressed the motility
      of A549 cells promoted by TGF-beta. LY294002, a specific inhibitor of
      phosphatidylinositol 3-kinase(PI3K)/Akt signaling, also suppressed TGF-beta
      induced motility and Akt phosphorylation. Sulindac sulfide and CAPE, but not
      curcumin, suppressed TGF-beta-induced Akt phosphorylation. We conclude that
      sulindac sulfide and CAPE suppress the motility promoted by TGF-beta in lung
      adenocarcinoma cells through the suppression of Akt. Our observations raise the
      possibility that these agents, except for (+)-catechin, can be applied not only
      as chemopreventive agents but also as anti-metastatic therapy.

PMID- 14691719
TI  - Alopecia congenita universalis, microcephaly, cutis marmorata, short stature and
      XY gonadal dysgenesis: variable expression of El-Shanti syndrome.
AB  - Alopecia congenita, laryngomalacia, and XY gonadal dysgenesis has been reported
      recently as a new syndrome in two unrelated Arab families from Jordan. We report
      a 4-year-old girl of first cousin Arab parents who had alopecia, microcephaly,
      cutis marmorata, short stature and borderline cognitive development. Karyotype
      analysis revealed a male constitution (46,XY) with no deletion of STSor SRY. She
      showed entirely normal female external genitalia and absence of female internal
      genitalia. Histological examination of the very small testicles found on
      laparascopy showed developed spermatic cords and paratesticular tissue with no
      testicular parenchyma, no Sertoli or Leydig cell development, and no seminiferous
      tubular development. Hormonal profile was that of a normal female child. Southern
      blotting and PCR assays showed an intact Y chromosome. Limited sequencing of the
      SRYgene revealed no mutations. CONCLUSION: this patient, together with the
      recently reported consanguineous families, represent a previously unrecognised
      autosomal recessive trait with pleiotropic effects including XY gonadal
      dysgenesis.

PMID- 14691720
TI  - A therapy-refractory neonatal auto-immune thrombocytopenia treated with anti-D.

PMID- 14691721
TI  - Expression pattern of the CCAAT/enhancer-binding proteins C/EBP-alpha, C/EBP-beta
      and C/EBP-delta in the human placenta.
AB  - The human trophoblast has the capacity to invade maternal tissue in a controlled
      fashion and to produce a wide range of hormones. The transcription factors
      belonging to the CCAAT/enhancer-binding protein (C/EBP) family are regulators of
      intracellular processes and mediators of hormone action. C/EBP binding sites have
      been described in the promoters of several placenta-expressed target genes. In
      the present study, we used immunohistochemistry and Western-blot analysis to
      investigate the expression pattern of the three most important members of this
      family, C/EBP-alpha, -beta, and -delta, in the normal human placenta as well as
      in isolated trophoblast cell populations. We found C/EBP-alpha and C/EBP-beta
      expression in the villous syncytiotrophophoblast (ST) and the extravillous
      (intermediate) trophoblast (EVT), but it was absent from the villous
      cytotrophoblast (CT). Interestingly, expression of C/EBP-beta continued to be
      very strong up to the third trimester of pregnancy, especially in the ST. C/EBP
      delta showed overall lower expression levels, stronger only in the EVT, while
      CT/ST showed very low/negative expression. These data show for the first time the
      expression pattern and tissue localization of C/EBP factors in the human
      placenta, indicating that these factors (especially C/EBP-beta) may play
      important roles in the regulation of placenta-specific genes and processes.

PMID- 14691722
TI  - Fascin-positive dendritic cells and fibroblastic reticulum cells build a
      framework of T-cell areas in lymph nodes.
AB  - Fascin, a 55-kDa actin-bundling protein, and alpha-smooth muscle actin (ASMA)
      were immunohistochemically examined in murine normal and stimulated lymph nodes.
      In specific pathogen-free young female mice, a few fascin-positive cells (FPCs)
      were located in the sinus and surrounding tissues, but ASMA-positive cells were
      undetectable. Following a subcutaneous injection of sheep red blood cells, the
      numbers of FPCs and their dendrites increased in the paracortex, with the
      accumulation of activated lymphocytes. Fibroblastic reticulum cells (FRCs),
      endothelial cells, histiocytic cells and lymphocytes in various stages of
      maturation were all fascin negative. These results indicated that fascin could be
      a reliable marker of paracortical dendritic cells in murine lymph nodes. However,
      FRCs became ASMA positive. Immunoelectron microscopy showed that the FPCs were
      interdigitating cells and that they closely contacted with FRCs. These two types
      of cells and reticular fiber formed a network in the paracortex and contacted
      with each other. In active paracortical response, both FPCs and FRCs are also
      stimulated and might play a significant role in the maturation of the
      lymphocytes.

PMID- 14691723
TI  - Immunohistochemical staining of protein kinase C isozymes (betaII and delta) is
      helpful to distinguish reactive follicles from follicular colonization of MALT
      lymphoma.

PMID- 14691724
TI  - Memory for actions: item and relational information in categorized lists.
AB  - Enacting action phrases in subject-performed tasks (SPTs) leads to better free
      recall than hearing or reading the same materials in verbal tasks (VTs). This
      enactment effect is usually explained by better item-specific information in SPTs
      than in VTs. The role of relational information is controversial. In the present
      paper, we will take the multiple recall approach to study the role of item and
      relational information in memory for actions by computing the number of item
      gains and the number of item losses over trials. This approach has previously
      been applied to lists of unrelated action phrases. We applied it to categorically
      related lists, also allowing a measure of relational information by clustering
      scores. It was found that SPTs produced more item gains than VTs. This finding
      confirmed the assumption that SPTs provide better item-specific information than
      VTs. The number of item losses did not differ between VTs and SPTs. This finding
      suggests that relational information is equally provided by VTs and SPTs.
      However, the organizational scores showed a more differentiated picture.
      Clustering was greater in SPTs than in VTs with randomly presented lists, but not
      with blocked lists. We suggested that these results, as well as other findings
      from the literature, could be explained by distinguishing automatic and strategic
      processes and the types of item associations that are addressed by these
      processes.

PMID- 14691725
TI  - Functional characterization of the pentapeptide QYNAD on rNav1.2 channels and its
      NMR structure.
AB  - The endogenous pentapeptide QYNAD (Gln-Tyr-Asn-Ala-Asp) is present in human
      cerebrospinal fluid (CSF), and its concentration is increased in demyelinating
      diseases. QYNAD was synthesized and its action on the rNav1.2 voltage-gated
      sodium channel alpha-subunit was studied using whole-cell recordings in a
      heterologous expression system. The effects were seen only upon equilibration of
      the peptide in the external bath solution for at least 10 min before the
      commencement of whole-cell experiments. The steady-state activation curve showed
      a rightward shift of 10 mV, while the steady-state inactivation curve showed a
      leftward shift of 5 mV. Frequency-dependent inhibition of the sodium current
      amplitude was observed at 2-10 Hz, in the presence of external QYNAD, but was not
      seen when applied internally. Fits of the whole-cell sodium current traces by
      Hodgkin-Huxley equations revealed subtle changes in the voltage-dependent rate
      constants governing the transition of the activation and the inactivation gates.
      Two dimensional NMR spectroscopy revealed the absence of medium and long-range
      Nuclear Overhauser effects (NOEs), which indicates that the peptide does not
      adopt any canonical secondary structure in solution. In summary, our studies show
      that although the pentapeptide QYNAD does not have a defined structure in
      solution, it has defined actions on the rNav1.2 voltage-gated sodium channel
      isoform.

PMID- 14691726
TI  - Magnetic resonance imaging of the ischaemic penumbra.
AB  - Acute cerebral ischaemia should no longer be considered a tragic untreatable
      event but a medical emergency. To be able to start therapy, imaging is needed to
      assess the presence of a potential penumbra, i.e. an area of the brain which is
      hypoperfused but not yet definitively infarcted. With the development of
      diffusion and perfusion MR techniques, the concept of a penumbra model has been
      developed in which it corresponds to the acute mismatch between diffusion and
      perfusion volumes. This penumbra should constitute the target for potential
      therapies.

PMID- 14691727
TI  - Chronic rhinosinusitis and neuropeptides.
AB  - The nose is an air conditioner and is involved in the protection of the lower
      airways against inhalation of exogenous particles and airborne irritants. The
      nasal mucosa is therefore densely innervated by sensory nerves containing several
      neuropeptides. In the airways, activation of sensory C and A? fibres leads to the
      release of multiple neuropeptides. In addition to their involvement in
      vasodilatation, plasma protein exudation and mucus secretion, sensory
      neuropeptides also participate in inflammatory cell recruitment. This neurogenic
      inflammation contributes to the intensity of nasal obstruction, rhinorrhea and
      headaches, the most common symptoms in chronic rhinosinusitis. The concentration
      of sensory neuropeptides is increased in the nasal mucosa of patients suffering
      from chronic rhinosinusitis. In contrast, the activity of the enzymes involved in
      the degradation of these sensory neuropeptides is markedly reduced. These
      observations should contribute to a better understanding of the
      pathophysiological mechanisms of one of the most frequently occurring chronic
      inflammatory diseases.

PMID- 14691728
TI  - Increased oxidative stress in patients with hydatidiform mole.
AB  - OBJECTIVE: The aim of this study was to determine the oxidative status and
      antioxidative status of plasma of patients with complete hydatidiform mole (CHM)
      and to compare these values with normal pregnancy. METHOD: Thirty-eight patients
      with CHM and 31 healthy pregnant women were enrolled in the study. To determine
      the antioxidative status of plasma, total antioxidant potential (TAOP) was
      calculated, and to determine the oxidative status of plasma total peroxide levels
      were measured. The ratio of TAOP to total peroxide was accepted as an indicator
      of oxidative stress. RESULTS: TAOP of plasma was significantly lower in patients
      with hydatidiform mole than in healthy pregnant women [mean (SD) values were
      511.9 (105.8) and 571.7 (109.4) micromol Trolox equiv./L respectively (p <0.05)].
      In contrast, mean (SD) total peroxide level of plasma was significantly higher in
      the patients [21.8 (6.4) micromol H2O2/L] than in healthy pregnant women [15.6
      (6.4) micromol H2O2/L (p <0.001)]. The mean oxidative stress index level was
      significantly higher in patients with CHM than in healthy pregnant women [4.43
      (1.70) versus 2.92 (1.50) respectively (p <0.001)]. CONCLUSION: Patients with CHM
      are exposed to oxidative stress, which may have a role in the pathogenesis of the
      disease. Supplementation with antioxidative vitamins such as C and E could be
      considered in treatment.

PMID- 14691729
TI  - Search for occult malignancy in patients with deep venous thrombosis. Results of
      a retrospective cohort study.
AB  - QUESTIONS UNDER STUDY: The association of deep vein thrombosis (DVT) and cancer
      is well established. It is controversial how large the association is and how
      extensive the evaluation for an underlying cancer should be. PRINCIPLES AND
      METHODS: 485 patients without a known cancer and a proven DVT formed the cohort
      of a retrospective study. Newly diagnosed (prevalent) cancers in patients with
      idiopathic (IDVT) and secondary (SDVT) during the index hospitalisation were
      compared and the contribution of the steps in an institutional tumour search
      program was analysed. The incidence of cancer in 204 patients with IDVT and 230
      patients with SDVT during follow-up was determined. RESULTS: During the index
      hospitalisation routine evaluation revealed eleven cancers in 236 patients (4.7%
      [95%-CI: 2.0-7.3]) with IDVT and five cancers in 249 patients (2.0% [95%-CI: 0.3
      3.7]) with SDVT. Combining patient history, clinical examination, routine
      laboratory tests and chest x-ray showed a sensitivity of 88% and a specificity of
      79% for the diagnosis of cancer. Abdominal ultrasound did not significantly
      increase the yield. 93% of the patients were followed for up to 5 years (mean 32
      months). Sixteen cancers occurred in 204 patients (7.8% [95%-CI: 4.0-11.5]) with
      IDVT and ten in 230 patients (4.35% [95%-CI: 1.7-7.0]) with SVDT (p<0.001).
      CONCLUSION: Prevalence and incidence of cancer were higher in IDVT patients
      compared to those with SDVT. Combining patient history, clinical examination,
      simple laboratory tests, and a routine chest x-ray is an appropriate strategy to
      detect underlying cancer in patients with IDVT. Routine abdominal ultrasound can
      safely be omitted.

PMID- 14691730
TI  - The PARK8 locus in autosomal dominant parkinsonism: confirmation of linkage and
      further delineation of the disease-containing interval.
AB  - Recently, a new locus (PARK8) for autosomal dominant parkinsonism has been
      identified in one large Japanese family. Linkage has been shown to a 16-cM
      centromeric region of chromosome 12, between markers D12S1631 and D12S339. We
      tested 21 white families with Parkinson disease and an inheritance pattern
      compatible with autosomal dominant transmission for linkage in this region.
      Criteria for inclusion were at least three affected individuals in more than one
      generation. A total of 29 markers were used to saturate the candidate region. One
      hundred sixty-seven family members were tested (84 affected and 83 unaffected).
      Under the assumption of heterogeneity and through use of an affecteds-only model,
      a maximum multipoint LOD score of 2.01 was achieved in the total sample, with an
      estimated proportion of families with linkage of 0.32. This LOD score is
      significant for linkage in a replication study and corresponds to a P value
      of.0047. Two families (family A [German Canadian] and family D [from western
      Nebraska]) reached significant linkage on their own, with a combined maximum
      multipoint LOD score of 3.33, calculated with an affecteds-only model (family A:
      LOD score 1.67, P=.0028; family D: LOD score 1.67, P=.0028). When a penetrance
      dependent model was calculated, the combined multipoint LOD score achieved was
      3.92 (family A: LOD score 1.68, P=.0027; family D: LOD score 2.24, P=.0007). On
      the basis of the multipoint analysis for the combined families A and D, the 1-LOD
      support interval suggests that the most likely disease location is between a CA
      repeat polymorphism on genomic clone AC025253 (44.5 Mb) and marker D12S1701 (47.7
      Mb). Our data provide evidence that the PARK8 locus is responsible for the
      disease in a subset of families of white ancestry with autosomal dominant
      parkinsonism, suggesting that it could be a more common locus.

PMID- 14691731
TI  - Dissection of genomewide-scan data in extended families reveals a major locus and
      oligogenic susceptibility for age-related macular degeneration.
AB  - To examine the genetic basis of age-related macular degeneration (ARMD), a
      degenerative disease of the retinal pigment epithelium and neurosensory retina,
      we conducted a genomewide scan in 34 extended families (297 individuals, 349 sib
      pairs) ascertained through index cases with neovascular disease or geographic
      atrophy. Family and medical history was obtained from index cases and family
      members. Fundus photographs were taken of all participating family members, and
      these were graded for severity by use of a quantitative scale. Model-free linkage
      analysis was performed, and tests of heterogeneity and epistasis were conducted.
      We have evidence of a major locus on chromosome 15q (GATA50C03 multipoint
      P=1.98x10-7; empirical P< or =1.0x10-5; single-point P=3.6x10-7). This locus was
      present as a weak linkage signal in our previous genome scan for ARMD, in the
      Beaver Dam Eye Study sample (D15S659, multipoint P=.047), but is otherwise novel.
      In this genome scan, we observed a total of 13 regions on 11 chromosomes (1q31,
      2p21, 4p16, 5q34, 9p24, 9q31, 10q26, 12q13, 12q23, 15q21, 16p12, 18p11, and
      20q13), with a nominal multipoint significance level of P< or =.01 or LOD > or
      =1.18. Family-by-family analysis of the data, performed using model-free linkage
      methods, suggests that there is evidence of heterogeneity in these families. For
      example, a single family (family 460) individually shows linkage evidence at 8
      loci, at the level of P<.0001. We conducted tests for heterogeneity, which
      suggest that ARMD susceptibility loci on chromosomes 9p24, 10q26, and 15q21 are
      not present in all families. We tested for mutations in linked families and
      examined SNPs in two candidate genes, hemicentin-1 and EFEMP1, in subsamples (145
      and 189 sib pairs, respectively) of the data. Mutations were not observed in any
      of the 11 exons of EFEMP1 nor in exon 104 of hemicentin-1. The SNP analysis for
      hemicentin-1 on 1q31 suggests that variants within or in very close proximity to
      this gene cause ARMD pathogenesis. In summary, we have evidence for a major ARMD
      locus on 15q21, which, coupled with numerous other loci segregating in these
      families, suggests complex oligogenic patterns of inheritance for ARMD.

PMID- 14691732
TI  - The effective mutation rate at Y chromosome short tandem repeats, with
      application to human population-divergence time.
AB  - We estimate an effective mutation rate at an average Y chromosome short-tandem
      repeat locus as 6.9x10-4 per 25 years, with a standard deviation across loci of
      5.7x10-4, using data on microsatellite variation within Y chromosome haplogroups
      defined by unique-event polymorphisms in populations with documented short-term
      histories, as well as comparative data on worldwide populations at both the Y
      chromosome and various autosomal loci. This value is used to estimate the times
      of the African Bantu expansion, the divergence of Polynesian populations (the
      Maoris, Cook Islanders, and Samoans), and the origin of Gypsy populations from
      Bulgaria.

PMID- 14691734
TI  - [Caenorhabditis elegans].

PMID- 14691733
TI  - Novel vitiligo susceptibility loci on chromosomes 7 (AIS2) and 8 (AIS3),
      confirmation of SLEV1 on chromosome 17, and their roles in an autoimmune
      diathesis.

PMID- 14691736
TI  - [The concept of catch bonds for molecular interactions].

PMID- 14691737
TI  - [A novel sense: emotional touch].

PMID- 14691738
TI  - [Heterochromatin: a deafening silence].

PMID- 14691739
TI  - [Ebola hemorrhagic fever: a unique efficacious vaccine dose in primates].

PMID- 14691740
TI  - [Interleukin-4 and muscle cell fusion].

PMID- 14691741
TI  - [Left-right asymmetry: Notch acts upstream of Nodal].

PMID- 14691742
TI  - [Insecticide resistance in the mosquito Culex pipiens].

PMID- 14691743
TI  - [Assembling nuclear pores at the end of the mitosis].

PMID- 14691744
TI  - [Prion disease: soluble dimeric prion protein binds PrPSc].

PMID- 14691745
TI  - [A worm's life].
AB  - Despite its relative anatomic simplicity, the nematode Caenorhabditis elegans (C.
      elegans) is a complex multicellular organism. In this review, we describe studies
      that have contributed to a better understanding of certain aspects of the worm's
      physiology. We focus on the cellular and molecular basis of the interaction
      between C. elegans and its environment, including its sensory capacities, the
      intrinsic biological clock that governs the speed of its life, and on some of the
      factors that control its life span. We also outline very recent findings that
      have demonstrated the existence of an innate immune system in C. elegans.
      Finally, we highlight a number of novel techniques that are transforming the worm
      from a largely genetic model system into an attractive organism for functional
      genomic studies.

PMID- 14691746
TI  - [C. elegans as a model for human inherited degenerative diseases].
AB  - The nematode C. elegans is an established model for developmental biology. Since
      the early 90's, this simple model organism has been increasingly used for
      studying human disease pathogenesis. C. elegans models based either on the
      mutagenesis of human disease genes conserved in this nematode or transgenesis
      with disease genes not conserved in C. elegans show several features that are
      observed in mammalian models. These observations suggest that the genetic
      dissection and pharmacological manipulation of disease-like phenotypes in C.
      elegans will shed light on the cellular mechanisms that are altered in human
      diseases, and the compounds that may be used as drugs. This review illustrates
      these aspects by commenting on two inherited degenerative diseases, Duchenne's
      muscular dystrophy and Huntington's neurodegenerative disease.

PMID- 14691747
TI  - [Usefulness of experimental models to understand the vascular effects of
      estrogens].
AB  - Hormonal replacement therapy does not prevent cardiovascular events in
      postmenopausal women. In contrast, the incidence of cardiovascular diseases is
      higher in men than in premenopausal women but increases in postmenopausal women,
      and all animal studies demonstrate a prevention of fatty streak deposit by
      estradiol. Although estradiol improves the lipoprotein profile, this effect can
      account for only a minor part of the protective effect. Endothelium appears to be
      an important target for estradiol, because this hormone potentiates endothelial
      nitric oxide (NO) production, thus promoting the beneficial effects of NO, such
      as vasorelaxation and inhibition of platelet aggregation. Estradiol accelerates
      endothelial regrowth, thus favoring vascular healing, and prevents apoptosis of
      endothelial cells. Estradiol prevents fatty streak deposit through a mechanism
      which is clearly independent of NO. The immuno-inflammatory system appears to
      play a key role in the development of fatty streak deposit as well as in
      atherosclerotic plaque rupture. Mice deficient either in monocyte-macrophages or
      in lymphocytes are partially protected against fatty streak deposit.
      Interestingly, the atheroprotective effect of estradiol is absent in mice
      deficient in T and B lymphocytes. Most of these effects of estradiol are mediated
      by estrogen receptor alpha, and are independent of estrogen receptor beta. Thus,
      the inflammatory-immune system appears to be also a major target of estrogens.
      However, the effects of estrogens on the immuno-inflammatory system appear
      ambiguous, as in some models, estradiol rather promotes inflammation (by
      increasing interferon gamma which could elicit plaque destabilization). A better
      understanding of the mechanisms of estrogens on the normal and atheromatous
      arteries is required and should help to optimize the prevention of cardiovascular
      disease after menopause.

PMID- 14691748
TI  - [Pathogenesis of Berger's disease: recent advances on the involvement of
      immunoglobulin A and their receptors].
AB  - Immunoglobulin A (IgA) nephropathy or Berger's disease is the most common form of
      primary glomerulonephritis in the world and one of the first cause of end-stage
      renal failure. IgA nephropathy is characterized by the accumulation in mesangial
      areas of immune complexes containing polymeric IgA1. While epidemiology and
      clinical studies of IgA nephropathy are well established, the mechanism(s)
      underlying disease development is poorly understood. The pathogenesis of this
      disease involves the deposition of polymeric and undergalactosylated IgA1 in the
      mesangium. Quantitative and structural changes of IgA1 play a key role in the
      development of the disease due to functional abnormalities of two IgA receptors:
      The FcalphaR (CD89) expressed by blood myeloid cells and the transferrin receptor
      (CD71) on mesangial cells. Abnormal IgA induce the release of soluble CD89 which
      is responsible for the formation of circulating IgA complexes. These complexes
      may be trapped by CD71 that is overexpressed on mesangial cells in IgA
      nephropathy patients allowing pathogenic IgA complex formation.

PMID- 14691749
TI  - [Communication between endothelial and smooth muscle cells].
AB  - Vascular endothelial cells play a fundamental role in the control of vascular
      tone, and therefore in the control of local blood flow, by releasing various
      contracting (endothelin, prostaglandins) and relaxing (prostacycline, NO)
      factors. An additional mechanism involving the hyperpolarization of the vascular
      smooth muscle cells is observed mainly in the coronary vascular bed and in the
      periphery. This phenomenon was attributed to an elusive endothelial factor called
      endothelium-derived hyperpolarizing factor (EDHF). This mechanism is now better
      understood. It involves first an increase in the endothelial intracellular
      concentration of calcium, the activation of endothelial potassium channels and
      the resulting hyperpolarization of the endothelial cells. The hyperpolarization
      of the endothelial cells is transmitted to the smooth muscle cells by different
      pathways. This hyperpolarization propagates along the vessels not only via the
      smooth muscle cells but also via the endothelial cells. Therefore, the
      endothelial layer can also be considered as a conducting tissue. The discovery of
      specific inhibitors of the endothelial cell hyperpolarization allows the
      assessment of the contribution of EDHF-mediated responses in the control of
      vascular tone.

PMID- 14691750
TI  - [Unexpected roles of the peptidyl-prolyl cis/trans isomerase Pin1].
AB  - Peptidyl-prolyl isomerases (PPIases) are chaperone enzymes which alter the
      peptide bond between a given amino acid and a proline, changing it from the cis
      to the trans conformation and vice versa. This modification can cause dramatic
      structural modifications which can affect the properties of targeted proteins.
      The ubiquitous PPIase Pin1, conserved from yeast to human, has been shown to be
      necessary for entry into mitosis. The yeast homologue, Ess1, is essential for
      cell survival. Pin1 possesses a WW domain which specifically recognizes pSer-Pro
      and pThr-Pro motifs in which the first amino acid is phosphorylated. Pin1 binds
      to many proteins implicated in cell cycle regulation (e.g. p53, Myt1, Wee1, and
      Cdc25C). Pin1 also targets tau, a protein forming part of hte neuronal
      cytoskeleton which is hyper-phosphorylated in patients suffering from Alzheimer's
      disease (AD). Pin1 could, therefore, be involved in the pathogenesis of Ad.
      Furthermore, Pin1 also binds two proteins involved in transcription: Rpb1, the
      largest subunit of RNA polymerase II and Spt5, a regulator of the elongation of
      transcription. Both theses proteins possess domains rich in S/T-P motifs which
      can be targeted by Pin1 when phosphorylated. Recent studies show that Pin1
      modulates the dephosphorylation of some proteins by allowing trans-specific
      phosphatases to recognize their target after isomerization. This unexpected role
      might allow protein regulation via peptidyl-prolyl isomerase activity.

PMID- 14691751
TI  - [p8 gene is necessary for tumor establishment].
AB  - We identified a new gene, called p8, which showed a strong induction during the
      acute phase of pancreatitis. Further experiments have shown that p8 mRNA is
      activated in response to several stresses and that its activation is not
      restricted to pancreatic cells. p8 is a nuclear protein and biochemical and
      biophysical studies showed that p8 was in many structural aspects very similar to
      the HMG (high mobility group) proteins, although sharing with them low amino acid
      sequence homology. Also, p8 was found overexpressed in many human cancers.
      Therefore, we wondered whether the p8-mediated response to cellular stress was
      necessary for tumor establishment. Subcutaneous or intraperitoneal injections of
      transformed p8-expressing fibroblasts led to tumor formation in nude mice, but no
      tumor was observed with transformed p8-deficient cells. Restoring p8 expression
      in transformed p8-deficient fibroblasts led to tumor formation demonstrating that
      p8 expression is necessary for tumor development and suggesting that the stress
      response mechanisms governed by p8 are required for tumor establishment.

PMID- 14691752
TI  - [Extreme divergence of a homeotic gene: the bicoid case].
AB  - Evolutionary developmental genetics (evo-devo) reveals that the plasticity of
      development is so important that every developmental biology project should
      carefully take this point into consideration. The example of bicoid, the first
      discovered morphogen, illustrates how an essential gene can change its function
      during evolution. The search for bicoid homologues showed that this gene is
      surprisingly specific to flies (cyclorraphan diptera) and absent in other
      insects. In fact, recent studies demonstrate that bicoid is a very derived Hox3
      homeotic gene. During insect evolution, the ancestral Hox3 gene lost its homeotic
      function and acquired new roles in oocytes and embryonic annexes. Then, in the
      lineage leading to modern flies, a duplication of this new gene, followed by
      functional divergence, led to the formation of bicoid and zerknullt. Both genes
      are located within the Drosophila Hox complex; however, they have no homeotic
      function. Thanks to the power of Drosophila genetics, it is possible to suggest
      that torso and hunchback may constitute the insect primitive anterior organizer.
      The bicoid evolutionary history reveals several fundamental mechanisms of the
      evolution of developmental genes, such as changes of gene regulation,
      modifications of protein sequences and gene duplication. It also shows the need
      for studying a wider range of model organisms before generalisations can be made
      from data obtained with one particular species.

PMID- 14691753
TI  - [Assembly of ribonucleoparticle complexes].
AB  - RNA-proteins interactions are involved in numerous cellular functions. These
      interactions are found in most cases within complex macromolecular assemblies.
      The recent development of tools and techniques to study RNA-protein complexes has
      significantly increased our knowledge in the nature of these specific
      interactions. The aim of this article is to present the different techniques used
      to study RNA-protein complexes, as well as recent data concerning the application
      of RNA as therapeutic molecules.

PMID- 14691754
TI  - [What is biomedicine? A socio-historical outline].
AB  - The article examines the debates surrounding the emergence of the term
      biomedicine, with a particular focus on the relation between the pathological and
      the normal. The authors reject simplistic definitions of biomedicine as a one-way
      street leading to the application of medical knowledge to medicine, or even as a
      two-way street characterized by iterative exchanges between the clinic and the
      laboratory. Rather, the authors introduce the notion of a biomedical platform as
      the site where the clinic and the laboratory intermingle and are realigned in
      connection with the ongoing process of medical innovation and the increasing
      automation of molecular procedures. The examples used in the article are drawn
      mainly from the field of onco-hematology.

PMID- 14691755
TI  - [Nobel Prize for Chemistry 2003. Water channels and ionic channels].

PMID- 14691756
TI  - [Every man desires to live long, but no one would be old].

PMID- 14691757
TI  - [Young onset Parkinson's disease and smoking: meta-analysis].
AB  - INTRODUCTION: Previous systemic reviews have reported a protective effect of
      smoking against Parkinson's disease (PD). However, the protective effect has not
      been examined before by any systemic review in patients with young onset PD.
      OBJECTIVE: Examine the association between young onset PD and tobacco smoking.
      MATERIAL AND METHODS: We conducted a meta-analysis including all published
      observational studies that investigated this association before January 2003. All
      languages were included with no restriction for year of publication. Risk
      estimate and its 95% confidence interval (95% CI) were extracted or calculated
      for all localized studies in patients with young onset PD. RESULTS: Five case
      control studies investigated the association between young onset PD risk and ever
      smoking. The fixed-effect pooled analysis was 0.55 (95% CI: 0.38 0.81), with
      insignificant homogeneity test. CONCLUSIONS: This meta-analysis shows a
      protective effect of tobacco smoking against young onset PD. Our results coincide
      with the other reviews which did not consider the age of diagnosis of PD.
      However, it is highly recommended prospective studies for the association between
      young onset PD risk and ever smoking

PMID- 14691758
TI  - [Evaluation of patients who do not visit neurology units].
AB  - AIMS: Our aim was to study the relation between non-attendance at neurology units
      and the delay that exists, as well as the demographic factors that may come to
      bear on non-attendance. PATIENTS AND METHODS: Data on neurology outpatients over
      the period between November and December 2002 were collected prospectively. Both
      patients who were referred for evaluation and those on their first programmed
      visit were included in the study. RESULTS: The total number of subjects was
      1,035, with an average age of 55.31 +/- 19.84 (14-96). Of these, 605 were females
      and 430 were males, with no significant differences in the age of the two groups.
      40% of the cases came from rural areas. 237 (22.9%) did not attend the visit. We
      found a statistically significant relation between age and non-attendance
      (t=2.67; p=0.008, Student's t). There was also a relation between not going to
      the visit and the delay that existed (t=5.84; p=0.000, Student's t). Patients who
      were referred from the Casualty department missed their visit more often those
      who were sent by their GP (Pi2=2.4; p=0.07, chi2). The date on which they
      received the appointment was also related to non-attendance (t=2.55; p=0.011,
      Student's t). CONCLUSIONS: Non-attendance was associated, above all, with the
      delay, with youth, being sent from casualty and with the length of time since
      they received notice of the visit.

PMID- 14691759
TI  - [Interictal EEG coherence in patients with partial temporal lobe epilepsy].
AB  - AIMS: The purpose of this research was to study the spatio-temporal
      characteristics of the correlation that exists between two simultaneous EEG
      signals (coherence) in the interictal period in patients with partial epilepsy
      that is presumably symptomatic of the temporal lobe (ILAE). PATIENTS AND METHODS:
      A study of 13 patients, aged between 17-60 years, was conducted (53% females). A
      digital EEG was performed on each patient using the 10/20 system of electrode
      location. 24 artifact-free segments were selected from the recording made in a
      rest-waking state with the patient's eyes closed. Fourier's transformation was
      employed to obtain cross spectrum matrices, which were then used to calculate the
      intrahemispheric (Cohintra) and interhemispheric (Cohinter) coherences expressed
      by the Z transformation. These values were ordered by regions considering the
      known anatomical connections. RESULTS: In both the overall and the individual
      analyses, we found greater alterations of the Cohintra and the Cohinter in the
      temporal regions, and there was a predominance of the left hemisphere. The
      individual analysis of coherence, unlike the visual interpretation of the EEG
      recording, showed significant alterations in all the patients in the sample.
      CONCLUSIONS: Incorporating this type of tool would enable us to reach a more
      accurate topographic diagnosis in cases of epilepsy of unknown aetiology. At the
      same time the possible means of medical and surgical treatment available would be
      widened.

PMID- 14691760
TI  - [Mirror writing secondary to left parietal-occipital infarction].
AB  - INTRODUCTION: Mirror writing is a rare disorder in which the patient's
      handwriting is done backwards and a mirror is needed to be able to read it.
      Although mirror writing presents both spontaneously and pathologically, it is
      mainly due to cerebrovascular lesions in the dominant hemisphere. CASE REPORT: A
      right-handed 62-year-old female who, following a left parietal-occipital
      infarction, evidenced by computerized tomography scanning, developed mirror
      writing with the left hand associated with mnemonic, gnosic and praxic disorders.
      The symptoms continued for a year after the episode. CONCLUSIONS: Mirror writing
      and other associated disorders are a consequence of a dysfunction of the left
      parietal-occipital lobe and the optic thalamus on the same side.

PMID- 14691761
TI  - [Transcranial Doppler during transient global amnesia].
AB  - INTRODUCTION: Transient global amnesia is a syndrome mainly characterised by an
      anterograde memory deficit, which disappears in less than 24 hours without
      leaving any kind of sequelae. Its aetiopathogenesis is still unclear. The
      ischemic theory became important after hypoperfusion was observed in the mesial
      region of the temporal lobe using different imaging techniques, although recently
      the use of diffusion-weighted magnetic resonance imaging by other authors has not
      revealed these alterations in the cerebral blood flow. CASE REPORT: We report on
      a transcranial Doppler study carried out in a female patient during the acute
      phase of the amnesia, with no evidence of hemodynamic alterations or significant
      asymmetries. Repeating the test after clinical recovery offered values that were
      similar to those of the previous study. CONCLUSIONS: It is posited that the basis
      of this process would not be related to ischemia but instead to a mechanism
      enabling spreading neurogenic depression that is similar to that which takes
      place during a migraine attack. Treatment with antiplatelet drugs would not,
      therefore, be recommended but calcium antagonists or beta blockers would be
      useful in preventing the clinical picture from being repeated.

PMID- 14691764
TI  - [HTLV-1 infection and Alzheimer-type dementia].

PMID- 14691765
TI  - [Hypopotassemia-linked radiculalgia].

PMID- 14691767
TI  - Future potential of endovascular techniques for vascular surgeons.
AB  - In his presidential address to the American Association for Vascular Surgery in
      2000, the late Dr. John Porter announced that there was insufficient time in the
      vascular training program to entertain endovascular technology because of the
      volume of vascular surgery techniques that must be learned. His philosophy
      accurately depicted the prevailing attitude of vascular surgical academia until
      very recently, and this restrictive stance has caused gradual but profound
      diminution in the caseload of vascular surgeons who are not trained in
      endovascular surgery techniques. Ultimately, the reluctance of vascular surgeons
      to expand their skill sets to include expertise in percutaneous interventions has
      enhanced the two competing disciplines of cardiology and radiology. As an early
      proponent of exploring endovascular therapy and its attendant tools and devices,
      my personal experience--both favorable and unfavorable--has provided me with a
      degree of perspective about the current status of endovascular surgery and enough
      background to speculate about the future role of the vascular surgeon in the
      treatment of arterial and venous disease. Parenthetically, it is encouraging that
      over the last few years, many educators in the field of vascular surgery have
      adopted a much more enlightened viewpoint regarding endovascular procedures.
      Hopefully, the pendulum has not already swung too far out of balance, and
      vascular surgeons will still have the opportunity to participate fully in the
      future of this exciting endovascular field. The following observations, ideas,
      and suggestions may pertain more to young trainees about to enter practice than
      to seasoned vascular surgeons.

PMID- 14691768
TI  - Essentials of endovascular surgery training: how to get started in carotid
      stenting.
AB  - Although early on vascular surgeons rebuked the concept that carotid stenting
      could stand up against the gold standard of carotid endarterectomy, this
      minimally invasive treatment for carotid bifurcation disease has been shown to
      have surprisingly low rates of periprocedural complications and is clearly
      favored by patients, for whom avoidance of surgery reigns paramount.
      Unfortunately, reluctance to embrace this and other emerging endovascular
      technologies, as well as a variety of other factors to be discussed, has left
      vascular surgeons poorly positioned to participate in the delivery of these
      therapies to their patients. With estimates of up to 75% of carotid stenoses
      being suitable for treatment by this new modality, and with carotid
      endarterectomy being the most commonly performed vascular operation in the United
      States today, this is a significant problem for our specialty and one badly in
      need of a solution. An understanding of the myriad of underlying interrelated
      problems helps to provide insight into possible solutions.

PMID- 14691769
TI  - Endovascular techniques in the treatment of acute limb ischemia: thrombolytic
      agents, trials, and percutaneous mechanical thrombectomy techniques.
AB  - Acute peripheral arterial occlusion is associated with great risk to the
      patient's limb and life. Failure to restore adequate arterial flow in a timely
      fashion can result in the development of irreversible tissue infarction and the
      opportunity for limb salvage is lost. On the other hand, patients with acute limb
      ischemia are often elderly and frail, and early invasive open surgical procedures
      without adequate preoperative stabilization and preparation result in an
      unacceptably high risk of perioperative cardiopulmonary complications and death.
      Percutaneous methods designed to remove the intraluminal thrombus offer an
      alternative to immediate open surgical revascularization. These less invasive
      techniques constitute an option that is better tolerated in medically compromised
      patients. The causative lesion can be precisely identified and the patency of
      outflow vessels can be restored. The lesion can then be addressed on an elective
      basis in a well-prepared patient, using percutaneous or open surgical techniques
      to effect a durable long-term solution. The treatment options include primary
      surgical revascularization, thrombolytic therapy, percutaneous mechanical
      thrombectomy, or a combination of any of the three. Clinicians who themselves
      have the skills to perform a wide assortment of interventions ranging from
      percutaneous therapies through open surgical revascularization are best able to
      arrive at the most rational option for treating a specific clinical scenario.
      This article is directed at providing the practicing surgeon with a basic fund of
      knowledge on the diagnostic and therapeutic strategies useful in treating
      patients with peripheral arterial occlusion. Only in this manner can we expect to
      reduce the high rate of morbidity and mortality that remains associated with
      these events.

PMID- 14691770
TI  - Digital fluoroscopy as a valuable adjunct to open vascular operations.
AB  - The increasing availability of and vascular surgeons' familiarity with digital
      cine-fluoroscopy in the operating room has been facilitated by the advent and
      growing popularity of endovascular aortoiliac aneurysm repair and other
      endovascular techniques that are being incorporated into vascular surgical
      practice. Digital cine-fluoroscopy can also be used as a valuable adjunct to
      standard open vascular procedures in several ways including: performance of
      completion angiography, fluoroscopically-assisted thromboembolectomy,
      intraoperative planning angiography, fluoroscopically-guided pressure gradient
      measurements, achieving vascular control of proximal arteries, intraoperative
      thrombolysis of compromised outflow tracts, and angioplasty and stenting of
      lesions detected intraoperatively. These techniques can improve the outcome of
      standard vascular procedures by permitting the identification of inflow, outflow,
      conduit, and anastomotic defects intraoperatively and guiding their repair.
      Additionally, in many cases they can reduce the amount of exposure required,
      reduce intraoperative blood loss, and minimize trauma to vessels during
      thrombectomy. Fluoroscopic guidance can facilitate and improve these and other
      aspects of standard open vascular procedures. Conversely, the ability to perform
      open interventions can facilitate the performance of many endovascular
      interventions. It is becoming increasingly important to be facile with both open
      and E fluoroscopically guided techniques in order to fully treat the spectrum of
      vascular disease in an optimum fashion.

PMID- 14691771
TI  - Iliac angioplasty and stenting in association with infrainguinal bypasses: timing
      and techniques.
AB  - Inflow iliac artery balloon angioplasty may be performed simultaneously with open
      infrainguinal vascular reconstruction in patients with multilevel occlusive
      disease of the lower extremity. This approach is safe, effective, has
      satisfactory long-term results, and should be part of the vascular armamentarium.

PMID- 14691772
TI  - Value, limitations, and techniques of renal artery stenting.
AB  - Percutaneous therapy for renovascular occlusive disease has become the preferred
      alternative to open renal artery revascularization. Angioplasty and stenting of
      renal artery stenoses has been shown to be a safe and effective option for severe
      hypertension and ischemic nephropathy. Catheter-based treatment, especially when
      performed with lower-profile systems can be performed with minimal morbidity and
      a reliably high degree of initial technical success. The long-term beneficial
      effects on blood pressure control and renal function, while debated, appear to be
      valid. In this article, data supporting the value and limitations of renal artery
      stenting are reviewed, and our technique for renal artery stenting using a lower
      profile platform of balloons and stents is described.

PMID- 14691773
TI  - Rationale and status of randomized controlled clinical trials in carotid artery
      stenting.
AB  - Efficacy for carotid artery stenting (CAS) has not been confirmed by randomized
      clinical trial methodology. Although carotid endarterectomy (CEA) is considered
      the preferred method for carotid revascularization in the management of patients
      with asymptomatic and symptomatic extracranial carotid occlusive disease,
      comparisons between CAS and CEA are now underway. In North America, the CREST
      (Carotid Revascularization Endarterectomy versus Stent Trial) protocol is now
      completing credentialing cases as randomization of cases is initiated. In Europe,
      the CAVATAS (Carotid and Vertebral Artery Transluminal Angioplasty Study) and
      SPACE (Stent Protected Angioplasty versus Carotid Endarterectomy) trials are
      recruiting symptomatic patients for randomization between CEA and CAS. It is
      anticipated that these trials will publish definitive results within the next 1-3
      years and help guide the referral of patients for CAS and CEA in the future.

PMID- 14691774
TI  - Critical analysis of distal protection devices.
AB  - There is considerable evidence that embolization takes place universally during
      all carotid stenting procedures. In addition, the development of sophisticated
      distal protection devices and their availability made the concept of cerebral
      protection widely acceptable, and currently there is a consensus among
      specialists that protection devices need to be used routinely. The results of the
      SAFER trial as well as the SAPPHIRE trial have further increased the enthusiasm
      for routine use of protection devices. However, each additional step to an
      existing procedure adds potential risks to the procedure. This is true for
      cerebral protection devices. The problems associated with the use of a distal
      protection device relate to (1) difficulties in introducing and deploying the
      device, (2) effectiveness of emboli capture, (3) protection device induced vessel
      injury, and (4) difficulties in retrieving the device. This article reviews the
      early clinical experience with various protection devices and summarizes some of
      the disadvantages of these devices.

PMID- 14691775
TI  - Endovascular grafts and other catheter-directed techniques in the management of
      ruptured abdominal aortic aneurysms.
AB  - Abdominal aortoiliac aneurysms that are ruptured and treated with open surgical
      repair have high morbidity and mortality rates. We have employed endovascular
      approaches to treat this entity since 1994. Patients with presumed ruptured
      aortoiliac aneurysms were treated with restricted fluid resuscitation
      (hypotensive hemostasis), transport to the operating room, placement under local
      anesthesia of a brachial or femoral guidewire into the supraceliac aorta and
      arteriography. If aortoiliac anatomy was suitable, an endovascular graft repair
      was performed. If the anatomy was unfavorable, the aneurysm was repaired in a
      standard open fashion. Only if circulatory collapse occurred was a supraceliac
      balloon placed and inflated using the previously positioned guidewire. Of 36
      patients so managed, 30 underwent endovascular graft repair and six required open
      repair. Four patients died within 30 days (operative mortality = 11%). Only 10
      patients required supraceliac balloon control. Endovascular grafts, when combined
      with hypotensive hemostasis and other endovascular techniques, including proximal
      balloon control, may improve treatment outcomes with ruptured abdominal
      aortoiliac aneurysms. These techniques should become widely used for the
      treatment of ruptured aneurysms.

PMID- 14691780
TI  - Factors associated with the use of pharmacologic agents to facilitate out-of
      hospital endotracheal intubation.
AB  - OBJECTIVE: To identify a set of clinical factors most strongly associated with
      the use of drug-facilitated intubation (DFI) in the out-of-hospital setting.
      METHOD: The authors used data from a prospective, multicentered endotracheal
      intubation (ETI) observational cohort trial, including patients from 45 emergency
      medical services in Pennsylvania. Providers reported clinical, physiologic, and
      anatomic factors associated with each ETI effort. The authors included only data
      from the 23 services using DFI. They identified all non-arrest (presence of a
      pulse) adult patients. They included both successful and failed ETIs. They
      defined DFI cases as patients who received a sedative or neuromuscular-blocking
      agent to facilitate ETI. The authors also classified patients who underwent
      nasotracheal intubation as DFI. They defined control subjects as patients
      undergoing conventional oral ETI. They performed multivariate logistic regression
      to identify the clinical, physiologic, and anatomic factors characteristic of
      DFI. They examined alternate forms of the final prediction model. RESULTS: The
      authors analyzed data from 208 nonarrest patients, including 92 DFIs and 116
      control subjects. Of 34 factors potentially related to DFI, 17 were excluded on
      univariate analysis (likelihood ratio p>0.25). Multivariate logistic regression
      revealed the following as positively associated with DFI: presence of clenched
      jaw/trismus (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.10-4.95;
      p=0.026); increased verbal Glasgow Coma Scale score (OR, 1.71; 95% CI, 1.29-2.26;
      p<0.001); use of cervical spine precautions (OR, 2.30; 95% CI, 1.15-4.62;
      p=0.018). Anterior vocal cords (OR, 0.27; 95% CI, 0.10-0.71; p=0.004) and
      laryngospasm (OR, 0.14; 95% CI, 0.02-1.17; p=0.025) were negatively associated
      with DFI. The model showed good fit (Hosmer-Lemeshow p=0.75) and discrimination
      (area under the curve=0.76). CONCLUSIONS: The authors identified a set of
      predictors strongly associated with DFI. These data offer insight into the
      current use of DFI and support the development of consensus-based guidelines for
      this procedure.

PMID- 14691781
TI  - The location and incidence of out-of-hospital cardiac arrest in Georgia:
      implications for placement of automated external defibrillators.
AB  - OBJECTIVE: Prior studies of automated external defrillator placement strategies
      for public access defibrillation (PAD) have addressed only the venue of out-of
      hospital cardiac arrest (OOHCA) in large urban areas. This study evaluates the
      relationship between population density and the incidence and location of OOHCA.
      METHODS: This study was a retrospective analysis of 624,199 Georgia state
      emergency medical services patient care reports (PCRs) in 2000. The PCR
      categorized these cardiac arrests by county into 12 location options. Counties
      were divided into population densities of <100, 100-400, 400-1,000, and >1,000
      persons per square mile. The incidence of cardiac arrest for each location type
      was calculated for each population density group. RESULTS: The <100 density group
      had only 21.77% of the state's population but 30.96% of the state's cardiac
      arrests, whereas the >1,000 density group had 35.46% of the population but only
      23.55% of the cardiac arrests (p<0.0001). The relative risk (95% confidence
      interval) for OOHCA in the <100 density group compared with the >1,000 density
      group was 2.14 (2.00, 2.29). The percentage of OOHCAs that occurred in the home
      for each population density group was: <100 persons per square mile, (67.67%);
      100-400 persons per square mile, (68.83%); 400-1,000 persons per square mile,
      (65.75%); and >1,000 persons per square mile (62.09%) (p=0.0001). CONCLUSIONS:
      There are variations in incidence and location of OOHCA based on population
      density in Georgia. As population density increases, the incidence percentage of
      OOHCAs decreases. However, as population density increases, there is an increase
      in the percentage of cardiac arrests occurring outside the home, where more
      OOHCAs could potentially benefit from PAD.

PMID- 14691782
TI  - Endotracheal intubation and esophageal tracheal Combitube insertion by regular
      ambulance attendants: a comparative trial.
AB  - OBJECTIVE: Recent cardiac arrest resuscitation guidelines have recommended the
      esophageal tracheal Combitube (ETC) as an advanced airway management alternative
      for individuals who infrequently perform endotracheal intubation (ETI). This
      study attempted to analyze basic (nonparamedic) ambulance attendant success rates
      at ETI and ETC insertion as well as their continuing skill competency over time
      and whether ongoing practice on mannequins improved skill performance. METHODS:
      Three hundred fifty-seven adult patients in cardiorespiratory arrest were treated
      by 81 basic ambulance attendants. Original study design called for the analysis
      of two treatment options in three patient groups: ETC insertion, ETI insertion
      with mannequin practice (ETI-MP), and ETI insertion without mannequin practice
      (ETI-NMP). The main outcome measures were:successful insertion and ventilation
      with ETC or ETI, assessed by receiving physicians; and differences in successful
      insertion/ventilation between the MP and NMP groups. RESULTS: Successful
      insertion (intent-to-treat) for the ETI-NMP group was 70 of 111 (63%; 95%
      confidence interval [CI], 54-73%); ETI-MP success was 105 of 139 (76%; 95% CI, 67
      84%); ETC-NMP success was 26 of 42 (62%; 95% CI, 49-75%); and ETC-MP success was
      36 of 53 (68%; 95% CI, 54-82%). Continuing mannequin practice appeared to improve
      ETI success (as-treated): MP 75% versus NMP 61% (odds ratio, 2.1; 95% CI, 1.11
      3.94). CONCLUSIONS: There were similar rates of successful insertion/ventilation
      with the ETC and ETI. ETI insertion success was lower without mannequin practice.
      ETI skill erosion was partially mitigated by additional field experience.

PMID- 14691783
TI  - A standing-order protocol for cricothyrotomy in prehospital emergency patients.
AB  - OBJECTIVE: To study utilization, indications, and outcomes associated with the
      use of a statewide, emergency medical services (EMS) standing-order protocol for
      cricothyrotomy. METHODS: A statewide EMS database was queried for patients who
      received cricothyrotomy under a standardized, standing-order protocol. Patient
      EMS and hospital records were reviewed in a defined sequence with information
      recorded on a standardized collection form. RESULTS: EMS records included eight
      years of practice with 1.5 million patient encounters. For each year studied,
      approximately 540 emergency medical technicians (EMTs) were certified to perform
      cricothyrotomy. State EMS providers performed a collective mean of eight
      cricothyrotomy procedures per year (range, 1-17), for a total of 68
      cricothyrotomies performed within the eight-year period. Hospital records were
      available for review in 61 patients. Fifty-six patients received cricothyrotomy
      by open surgical incision, six by needle with jet ventilation, and one by both
      methods. Categorization of cricothyrotomy patients as trauma or medical was 61%
      trauma and 39% medical. Thirty-six patients (59%) were in cardiac arrest on EMS
      arrival and 12 patients (20%) died during transport. Thirteen trauma patients
      (21%) were admitted with eight patients surviving to discharge (13%). The
      neurologic impairment at time of hospital discharge was severe in four, moderate
      in two, and minimal or none in two patients (3%). CONCLUSION: A considerable
      percentage of cricothyrotomy procedures were performed on patients with non
      trauma-related diagnoses in this investigation describing a standing-order EMS
      protocol for cricothyrotomy. The majority of patients undergoing cricothyrotomy
      with this protocol were in cardiac arrest at the time of cricothyrotomy, with a
      small minority of patients surviving to hospital discharge and fewer surviving
      neurologically intact.

PMID- 14691784
TI  - The use of national highway traffic safety administration uniform prehospital
      data elements in state emergency medical services data collection systems.
AB  - OBJECTIVE: Although the concept of emergency medical services (EMS) has existed
      for 30 years, there is little scientific evidence validating its impact on
      morbidity and mortality. A significant barrier to conducting meaningful
      assessments relates to the lack of reliable and uniform EMS data. The objective
      of this study was to determine the extent to which states incorporate the Uniform
      Prehospital EMS Data Elements into statewide EMS data collection systems.
      METHODS: Study investigators requested and compared data elements from all states
      with a statewide prehospital data collection system. RESULTS: During the study
      period, 43 states with statewide EMS data collection systems captured, on
      average, 79% of the Uniform Prehospital EMS Data Set. Variables considered
      essential to EMS evaluation were more likely collected (84%) than variables
      considered desirable (72%). Only eight (10%) of the 81 uniform data elements are
      collected by all 43 participating states. CONCLUSIONS: Findings suggest that
      related EMS data variables are collected by the majority of states across the
      country. This degree of similarity provides a foundation for establishing common
      fields that can be used to develop a national EMS registry.

PMID- 14691785
TI  - Albuterol sulfate administration by EMT-basics: results of a demonstration
      project.
AB  - OBJECTIVES: 1) To evaluate the ability to train emergency medical technicians
      basic (EMT-Bs) to accurately identify bronchospasm and, based on a treatment
      protocol, administer albuterol sulfate via nebulization as a standing order. 2)
      To measure the improvement in patient condition after treatment. METHODS:
      Following approval by the Commissioner of Health and Institutional Review Board,
      EMS agencies were enrolled to participate in the study and EMT-Bs were trained
      using a four-hour curriculum. For each patient, a prehospital data collection
      form was completed including identifying data for the EMT-B, patient assessment,
      and history information; and pre- and posttreatment assessments and a hospital
      data collection form were completed including the emergency department
      physician's diagnosis, assessment of bronchospasm, number of albuterol treatments
      received in the emergency department, and final disposition of the patient.
      RESULTS: During a one-year study period, EMT-Bs treated 190 patients as part of
      the project. Across all values patients showed a clinical improvement as a result
      of the therapy. Concurrence in the assessment of bronchospasm by the EMT-B with
      an emergency department physician was found in 87.4% of the cases. When including
      allergic reaction, anaphylaxis, bronchiolitis, and chronic obstructive pulmonary
      disease in the diagnosis list of bronchospasm, the accuracy rate increased to
      more than 94%. CONCLUSION: This study indicated EMT-Bs were highly successful in
      their evaluation of bronchospasm. Based on this level of accuracy, the authors
      suggest that it is safe for emergency medical service systems and medical
      directors to develop protocols that allow EMT-Bs to administer albuterol via
      nebulizer for bronchospasm based on their assessment.

PMID- 14691786
TI  - The effect of simple interventions on paramedic aspirin administration rates.
AB  - OBJECTIVE: To determine the baseline rate of aspirin administration by paramedics
      and to assess the effect of two interventions (protocol change and brief
      educational intervention) on that rate. METHODS: The advanced life support
      transport provider's clinical database was retrospectively queried to identify
      calls involving adult patients with chest pain or paramedic impression of
      suspected cardiac event (possible acute coronary syndrome [ACS]). The study
      includes data from January 1, 1999, to June 30, 2002, which was divided into
      three distinct periods. Period 1 was the baseline, period 2 was after the
      protocol change intervention, and period 3 was after the brief educational
      intervention. The chest pain protocol indicates patients with chest pain should
      be treated with aspirin. RESULTS: During period 1, 548 of 3,635 (15.1%) patients
      with possible ACS received aspirin. During period 2, 1,941 of 7,236 (26.8%)
      patients with possible ACS received aspirin (chi(2) p<0.0001; odds ratio
      [OR]=2.06; 95% confidence interval [CI]=1.86-2.29). During period 3, 749 of 2,026
      (37%) patients with possible ACS received aspirin (chi(2) p<0.0001; OR=1.60; 95%
      CI=1.44-1.78). Comparing period 1 with period 3, after both interventions, there
      was a 22% absolute improvement in aspirin administration rates (chi(2) p<0.0001;
      OR=3.30; 95% CI=2.91-3.76). CONCLUSION: Aspirin is underutilized in treating
      patients with suspected ACS. Two brief interventions can lead to modest increases
      in aspirin administration rates. Even after these interventions, aspirin
      administration rates remain low.

PMID- 14691787
TI  - The Los Angeles Motor Scale (LAMS): a new measure to characterize stroke severity
      in the field.
AB  - OBJECTIVE: To develop and retrospectively analyze an instrument that rapidly
      characterizes pretreatment stroke severity for use in prehospital acute stroke
      clinical trials. METHODS: The Los Angeles Motor Scale (LAMS) was constructed by
      assigning point values to Los Angeles Prehospital Stroke Screen (LAPSS) items of
      facial weakness, arm strength, and grip to yield a total 0-5 scale. The
      concurrent, discriminant, and predictive validities of the LAMS were probed using
      data from 90 patients enrolled in acute stroke clinical trials. Predictive
      performance of the LAMS was compared with that of the initial full National
      Institutes of Health Stroke Scale (NIHSS) and the five-item shortened NIHSS
      (sNIHSS) in projecting long-term outcomes on standard functional end points.
      RESULTS: LAMS score at entry averaged mean 2.6, median 2. Entry LAMS scores
      correlated closely with entry NIHSS scores (r=0.75). LAMS score correlations with
      three-month functional outcome measures were robust. Receiver operator curve
      analyses (c statistic) for performance in predicting three-month outcomes were:
      three-month modified Rankin-LAMS 0.75, sNIHSS 0.69, NIHSS 0.74; three-month
      Barthel Index-LAMS 0.77, sNIHSS 0.76, NIHSS 0.82; three-month NIHSS-LAMS 0.76,
      sNIHSS 0.62, NIHSS 0.70; and three-month GOS-LAMS 0.55, sNIHSS 0.67, NIHSS 0.76.
      Considering dichotomized three-month measures, entry LAMS scores were markedly
      lower in patients destined for excellent outcome, e.g., three-month modified
      Rankin score<or=1, mean entry LAMS score 2.2 versus 3.7, p=.0002. CONCLUSIONS: A
      motor score derived from the LAPSS rapidly quantifies stroke severity in the
      field and predicts functional outcomes with accuracy comparable to that of the
      full NIHSS and the sNIHSS.

PMID- 14691788
TI  - Prehospital emergency care in Abu Dhabi, United Arab Emirates.
AB  - Once a harsh land with limited resources, the United Arab Emirates (UAE) has
      undergone considerable change over the 50 years after the discovery of vast
      natural gas and petroleum reserves. In addition to significant economic and
      societal changes, remarkable improvements have been made in the provision of
      health care services, including expanded health care infrastructure, human
      resource development, and decreased infectious disease morbidity and mortality.
      Emergency medicine (EM) and emergency medical services (EMS) within the country
      are currently limited, with the UAE best described as being in the "developing"
      phase of EM. Within the capital city, Abu Dhabi, the Ministry of Health, Civil
      Defense, and police provide the majority of EMS services. At the present time,
      there are no uniform medical control or treatment protocols, communications
      systems, systems management, training or education, or quality assurance
      policies. However, the recent advancements in health care, and a developing
      practice of and interest in EM, may lead to improved EMS and prehospital care.

PMID- 14691789
TI  - Recommended guidelines for uniform reporting of data from out-of-hospital airway
      management: position statement of the National Association of EMS Physicians.

PMID- 14691793
TI  - A tribute to Peter Safar, MD: Physician, researcher, mentor, visionary, humanist.

PMID- 14691892
TI  - Medication reconciliation: a practical tool to reduce the risk of medication
      errors.
AB  - Preventable adverse drug events are associated with one out of five injuries or
      deaths. Estimates reveal that 46% of medication errors occur on admission or
      discharge from a clinical unit/hospital when patient orders are written. This
      study was performed to reduce medication errors in patient's discharge orders
      through a reconciliation process in an adult surgical intensive care unit (ICU).
      A discharge survey was implemented as part of the medication reconciliation
      process. The admitting nurse initiated the survey within 24 hours of ICU
      admission and the charge nurse completed the survey on discharge. Baseline data
      were obtained through a random sampling of 10% of discharges in first 2 weeks of
      the study (July 2001-May 2002). Medical and anesthesia records were reviewed,
      allergies and home medications verified with patient/family and findings compared
      with orders at time of ICU discharge. Baseline data revealed that 31 of 33 (94%)
      patients had orders changed. By week 24, nearly all medication errors in
      discharge orders were eliminated. In conclusion, use of the discharge survey in
      this medication reconciliation process resulted in a dramatic drop in medications
      errors for patients discharged from an ICU. The survey is now a part of our
      electronic medical record and used in 4 adult ICUs and 2 medicine floors.

PMID- 14691893
TI  - Intensive care outflow limitation--frequency, etiology, and impact.
AB  - OBJECTIVE: To assess the frequency, causes, and effect of unsuccessful discharge
      decisions from the ICU. SETTING: An 11-bed general intensive care unit of a 750
      bed urban university hospital, tertiary referral center and level one trauma
      center. DESIGN: A prospective, observational study. PATIENTS: All ICU patients
      judged appropriate for discharge by the ICU attending physician. MEASUREMENTS AND
      RESULTS: A total of 856 attempted discharges in 706 patients were analyzed over
      16 months. Of these, 703 (82%) were successful within 24 hours. Of the remaining
      153 unsuccessful discharges, 51 (33%) were deferred because of medical
      deterioration, 32 (21%) at the request of the ward physicians or nurses and 70
      (46%) because of administrative difficulties (lack of ward bed space or
      disagreement over admitting service). When compared to patients successfully
      discharged on the first attempt, those whose discharge was deferred had a
      significantly longer ICU admission prior to the first discharge attempt (median
      4d v 3d, P =.009), and a higher proportion required intermediate care (48% v 26%,
      P <.001). Both these factors were independently associated with unsuccessful
      discharge in a logistic regression analysis (OR 1.04, 95%CI 1.02, 1.06, P =.0001,
      OR 2.05 95%CI 1.30, 3.26, P =.002, respectively). Deferred discharges accounted
      for 153 days of ICU care (2.6% of the total) and were associated with ICU
      overflow on 118 days (2% of all ICU days). CONCLUSION: ICU outflow limitation
      occurs in up to 1 in 6 discharges. It can be due to medical deterioration, level
      of care issues or administrative problems, and may lead to inefficient use of ICU
      resources.

PMID- 14691894
TI  - Do we need a systematic activation of alarm soundings for blood pressure
      monitoring for the safety of ICU patients?
AB  - PURPOSE: Evaluation of a protocol of activation-deactivation of alarm soundings
      on noninvasive mean arterial pressure (MAP) monitoring. MATERIALS AND METHODS:
      103 patients were analyzed. Alarm soundings on noninvasive MAP were either
      activated (group A) or inactivated (group NA) according to a protocol based on
      patient's hemodynamic status. RESULTS: In the first part of the study (11 periods
      of 24 hours), we informed the nursing staff before data collection. In the second
      part of the study (11 periods of 24 hours), we did not inform the nursing staff
      before data collection. Results of the two parts were assembled and the final
      analysis consisted of 3,304 hours of monitoring with 12,839 noninvasive MAP
      measurements, 6,354 in group A and 6,485 in group NA. In group A, 75 of 944 (8%)
      of abnormal measurements were detected or managed with a delay > 15 minutes and
      among them 16 required a therapeutic adjustment. In group NA, 140 of 265 (53%) of
      abnormal measurements were detected or managed with a delay > 15 minutes and
      among them, only one required a therapeutic adjustment. The number of alarm
      soundings avoided in group NA was 286. CONCLUSION: In this study, a systematic
      activation of alarm soundings for non-invasive blood pressure monitoring seemed
      unnecessary for the safety of ICU patients.

PMID- 14691895
TI  - Cost-effectiveness of drotrecogin alfa (activated) for the treatment of severe
      sepsis in Germany.
AB  - Drotrecogin alfa (activated) (Xigris; Eli Lilly and Company, Indianapolis, IN)
      significantly reduced mortality in severe sepsis in the PROWESS trial. We
      evaluate the cost-effectiveness of drotrecogin alfa (activated) as an adjunct to
      standard therapy from the German healthcare payer's perspective with respect to
      patients with 1) severe sepsis and 2) severe sepsis and multiple organ failure
      the approved European indication. Hospital resource use based on PROWESS was
      valued using German unit costs. German life-tables and long-term survival
      assumptions determined life-years gained. European and German healthcare resource
      use data are examined in the sensitivity analysis. We assumed a unit price of
      euro;237.50 for drotrecogin alfa (activated). Per patient treated, drotrecogin
      alfa (activated) increased costs by euro;7,500, and hospital costs by euro;900
      for all patients (euro;7,400 and euro;1,500 respectively for the approved
      indication) and survival by 0.59 life years (0.87 life years respectively for the
      approved indication). Thus drotrecogin alfa (activated) cost euro;14,100
      (euro;17,700 discounting life years at 3%) per life year gained for all patients
      (euro;10,200 and euro;12,900, respectively, for the approved indication). Testing
      the unit cost of drotrecogin alfa (activated), pattern of resource use, and
      survival benefit, demonstrated that cost-effectiveness lies well within the range
      of other life saving interventions in Germany representing good economic value.

PMID- 14691896
TI  - Prevention of venous thromboembolism in critically ill medical patients: a Franco
      Canadian cross-sectional study.
AB  - BACKGROUND: Medical intensive care unit (ICU) patients are at moderate risk of
      venous thromboembolism (VTE) and prophylaxis against VTE is recommended.
      OBJECTIVES: To observe the range and frequency of VTE prophylaxis administered to
      medical ICU patients and to determine factors associated with different
      strategies in French and Canadian ICUs. DESIGN: Prospective cross-sectional
      observational study. RESULTS: 113/251 (45.0%) French and 29/30 (96.6%) Canadian
      ICUs agreed to participate. Of 1,222 critically ill medical patients, most were
      mechanically ventilated (62.5%). Overall, heparin VTE prophylaxis was
      administered to 63.9% patients, similarly between the 2 countries. Excluding
      patients with contraindications to heparin and those receiving therapeutic
      anticoagulation, 91.7% of medical ICU patients appropriately received either low
      dose unfractionated heparin (UFH) or low molecular weight heparin (LMWH)
      prophylaxis. Independent predictors of heparin prophylaxis were invasive
      mechanical ventilation (odds ratio [OR]; 95%CI, 2.4 (1.4-4.3) and obesity (OR
      3.1; 1.1-8.8). LMWH was less likely to be prescribed for patients with renal
      failure (OR 0.1; 0.0009-0.9), or receiving antiembolic stockings (OR 0.4, 0.1
      0.9), and much more likely to be prescribed in French ICUs (OR 9.2; 5.0-16.9);
      however, among patients receiving LMWH, high doses were more likely to be
      prescribed in Canadian ICUs (OR 8.7; 2.0-37.6). Patients who were pregnant or
      postpartum (OR 7.7, 1.3-44.3), had neurologic failure (OR 2.1, 1.3-3.4), or were
      Canadian (OR 3.0, 2.1-4.4) were most likely to receive mechanical VTE prophylaxis
      (with antiembolic stockings or pneumatic compression devices), whereas those who
      were already receiving heparin were less likely to receive mechanical prophylaxis
      (OR 0.5, 0.3-0.7). CONCLUSIONS: In this binational cross-sectional observational
      study of medical ICU patients, we found that 92% of eligible patients received
      either UFH or LWMH for VTE prophylaxis. Differences in prescribing between
      countries include significantly greater use of LMWH in France, but use of lower
      doses than in Canada, and greater use of mechanical VTE prophylaxis in Canada.
      More randomized trials of VTE prophylaxis in critically ill medical patients
      would better inform practice.

PMID- 14691897
TI  - Non-neurological organ dysfunction in neurocritical care.
AB  - PURPOSE: To determine the incidence of non-neurological organ dysfunction in
      patients with severe neurological injury. MATERIALS AND METHODS: Modified daily
      SOFA (mSOFA) scores were retrospectively calculated for 55 consecutive patients
      with severe head injury or subarachnoid hemorrhage. mSOFA was defined as the sum
      of the 5 non-neurological component SOFA scores, maximum mSOFA as the sum of the
      most abnormal non-neurological SOFA component scores and delta mSOFA as the
      difference between maximum mSOFA and admission mSOFA. Organ failure was defined
      as a SOFA component score > or =3. RESULTS: Median (IQR) admission, maximum and
      delta mSOFA scores were 4 (3-6), 8 (6-9), and 2 (1-5), respectively. Respiratory
      and cardiac failure developed in 80% and 82% of patients, respectively. No
      patient developed renal or hepatic failure. Three patients developed
      hematological failure. There was no difference between survivors and nonsurvivors
      with respect to admission mSOFA (P =.45), maximum mSOFA (P =.54), or delta mSOFA
      (P =.19). There was no difference between those patients with favorable or
      unfavorable neurological outcome with respect to admission mSOFA (P =.24),
      maximum mSOFA (P =.84), or delta mSOFA (P =.20). CONCLUSIONS: Cardiopulmonary
      failure, as defined by SOFA, is common in intensive care unit patients with
      severe head injury and subarachnoid hemorrhage. In contrast to other intensive
      care unit patient populations, the mortality of patients with closed head injury
      or subarachnoid hemorrhage was not related to the severity of organ dysfunction
      on admission or its development during the intensive care unit stay.

PMID- 14691898
TI  - Reversible myocardial dysfunction, a possible complication in critically ill
      patients without heart disease.
AB  - PURPOSE: Reversible myocardial dysfunction or myocardial stunning is frequently
      described in patients with episodes of acute coronary syndrome and has recently
      been reported in critically ill patients without ischaemic heart disease. This
      article presents a study and description of the possible existence of myocardial
      dysfunction in critically ill patients in our setting who present no acute
      episode or history of cardiovascular disease. DESIGN: Prospective, descriptive
      study. SETTING: The intensive care unit of a district hospital. PATIENTS AND
      PARTICIPANTS: The study included all patients admitted to the intensive care unit
      between March 1998 and March 2001 for noncardiac causes and with no history of
      heart disease, and who underwent echocardiographic examination for
      electrocardiographic changes, signs of cardiac insufficiency, persistent
      arrhythmias, or any other indication. Patients with sepsis or other critical
      illness known to be associated with myocardial dysfunction were excluded from the
      study. The study was carried out on those selected patients who developed
      myocardial dysfunction. MEASUREMENTS AND RESULTS: Transthoracic and
      transoesophageal echocardiography were carried out to assess the left ventricular
      ejection fraction and any segmental contractility disturbances. These
      investigations were carried out within 24 hours of admission, during the first
      week, during the second or third week, after one month and after three to 6
      months. The electrocardiogram was assessed on admission and the changes over time
      were studied. Thirty-three patients were included in the study after detecting
      myocardial dysfunction; the median age of these patients was 63 years [range, 23
      82 years]. Seven patients died. The median initial left ventricular ejection
      fraction was 0.34 [range, 0.16-0.48] and improved with time. Segmental
      contractility disturbances were detected initially in all patients and also
      normalized with time. All patients presented electrocardiogram changes that
      normalised in line with the echocardiographic changes. CONCLUSIONS: Reversible
      myocardial dysfunction can be develop in critically ill patients without primary
      heart disease. This syndrome is associated with systolic dysfunction, segmental
      contractility disturbances and electrocardiographic changes.

PMID- 14691899
TI  - Quantification of lung water by transpulmonary thermodilution in normal and
      edematous lung.
AB  - PURPOSE: To analyze the accuracy of the transpulmonary thermodilution method in
      the determination of extravascular lung water (EVLW). MATERIAL AND METHODS: Acute
      lung injury was produced in eight adolescent pigs weighing 28 to 35 kg by
      bronchoalveolar lung lavage. EVLW was measured by transpulmonary thermodilution
      method before and after the intratracheal introduction of 250 or 500 mL of saline
      solution in different lung injury conditions. No corrections for anatomic dead
      space were made. RESULTS: When 250 mL was introduced, 195 +/- 17 mL was detected
      in normal (uninjured) lungs versus 74 +/- 57 mL in edematous (injured) lungs (P
      <.05). When 500 mL was introduced, 343 +/- 67 mL was detected in normal lungs
      versus 160 +/- 51 mL in edematous lungs (P <.001). Considering all determinations
      together, there was a very high negative correlation between the baseline EVLW
      and the percentage of EVLW detected (r = -0.92, P <.001). CONCLUSION: The
      transpulmonary thermodilution method is very accurate to detect changes in EVLW
      in normal lungs. In edematous lung, this method may underestimate the EVLW.

PMID- 14691905
TI  - Postinfectious glomerulonephritis complicating diabetic nephropathy: a frequent
      association, but how clinically important?

PMID- 14691906
TI  - Image quality issues in a static image-based telepathology consultation practice.
AB  - Field selection and image quality have often been identified as impediments in
      the successful employment of static-image telepathology. One thousand seven
      hundred fifty-three electronic consultations using static images were performed
      at the Department of Telemedicine, Armed Forces Institute of Pathology (AFIP)
      between November 1994 and September 2001, with 98.3% receiving a telepathology
      diagnosis. In 47.9% of cases, imagery was considered good by AFIP consultants,
      38.5% were considered adequate, and 14.6% of cases were considered to have poor
      quality imagery. Deficiencies in image quality were recorded for each case. Cases
      with imagery rated as good averaged significantly fewer deficiencies per case
      (0.45, range: 0 to 3) than cases with imagery rated adequate (0.95, range: 0 to
      6) or poor (2.4, range: 0 to 7). Deficiencies in focus were most commonly
      identified in this series of cases (28.1%), followed by improper white balancing
      of the capture device (14.1%) and inadequate resolution (10%). Cases in which
      images were of inadequate resolution showed an increased likelihood for
      discordance between the telepathology diagnosis and the diagnosis rendered on
      follow-up material ("truth diagnosis"). Inadequate field selection, although only
      cited in 6.7% of cases overall, was seen with a significantly higher frequency in
      cases in which there was discordance between the telepathology and truth
      diagnosis. A review of common image deficiencies in static-image telepathology
      and possible causes is presented.

PMID- 14691907
TI  - IgA-dominant acute poststaphylococcal glomerulonephritis complicating diabetic
      nephropathy.
AB  - Two pathological patterns of acute poststaphylococcal glomerulonephritis are well
      defined and include (1) an acute proliferative and exudative glomerulonephritis
      closely resembling classical acute poststreptococcal glomerulonephritis in
      patients with Staphylococcus aureus infection and (2) a membranoproliferative
      glomerulonephritis in patients with Staphylococcus epidermidis infection
      secondary to ventriculovascular shunts. In this study, we report a novel
      immunopathologic phenotype of immunoglobulin (Ig) A-dominant acute
      poststaphylococcal glomerulonephritis occurring in patients with underlying
      diabetic nephropathy. Five patients with type 2 diabetes presented with acute
      renal failure occurring after culture-positive staphylococcal infection. Renal
      biopsy disclosed an atypical pattern of acute endocapillary proliferative and
      exudative glomerulonephritis with intense deposits of IgA as the sole or dominant
      immunoglobulin, mimicking IgA nephropathy. The deposits were predominantly
      mesangial in distribution with few subepithelial humps. All five cases occurred
      superimposed on well-established diabetic nephropathy. Outcome was poor with
      irreversible renal failure in four of five (80%) cases. The possible
      pathophysiological basis of this atypical form of acute poststaphylococcal
      glomerulonephritis in diabetic patients is explored. Proper recognition of this
      entity is needed to avoid an erroneous diagnosis of IgA nephropathy, with
      corresponding therapeutic and prognostic implications.

PMID- 14691908
TI  - Cyclooxygenase-2 expression in stromal tumors of the gastrointestinal tract.
AB  - Cyclooxygenase (COX) is a key enzyme in the conversion of arachidonic acid to
      prostaglandins, prostacyclin, and thromboxane. COX-2 is expressed in many
      epithelial malignancies, particularly those of the gastrointestinal (GI) tract.
      COX-2 has been implicated in the pathogenesis of cancers and has a significant
      negative effect on survival. To date, little is known about the expression of COX
      2 in nonepithelial tumors. The objective of this study was to evaluate the
      expression of COX-2 in GI stromal tumors (GISTs). We evaluated 15 GISTs using
      tissue microarray. Tissue blocks were retrieved and stained with hematoxylin and
      eosin to evaluate the histological tumor type. In addition, immunohistochemistry
      was performed for COX-2, the macrophage marker, CD68 (KP-1), and KIT (CD117). Two
      pathologists then evaluated the tissues to determine the extent and intensity of
      COX-2 expression. The location of CD68-positive cells, and whether these cells
      were COX-2 positive, was also evaluated. The results showed that 80% (12 of 15)
      of the tumors expressed COX-2. Expression was noted in the cytoplasm of the tumor
      cells, with variable intensity of staining among the tumors. COX-2 was expressed
      in both epithelial cell and spindle cell tumors, but appeared stronger in
      epithelial lesions. In mixed lesions, COX-2 was expressed to a greater extent in
      epithelial areas. There was a greater extent of COX-2 expression in malignant
      tumors and tumors located within the stomach. Tumor-infiltrating macrophages
      (CD68-positive cells) were identified in all of the lesions; in 80% of cases,
      those macrophages also expressed COX-2. This study is the first to demonstrate
      COX-2 expression in stromal lesions of the GI tract. The enzyme may play a role
      in the proliferation of these lesions, suggesting the potential use of
      nonsteroidal anti-inflammatory drugs in treatment.

PMID- 14691909
TI  - Evidence of apoptosis in chronic alcoholic skeletal myopathy.
AB  - Apoptosis is a common mechanism of programmed cell death that has been implicated
      in the pathogenesis of alcohol-induced organ damage. Experimental studies have
      suggested alcohol-mediated apoptosis in cardiac muscle. The relationship between
      skeletal and cardiac muscle damage in alcoholism led us to consider the possible
      role of apoptosis in the pathogenesis of skeletal myopathy. We prospectively
      evaluated apoptosis in skeletal muscle biopsies of 30 consecutively selected male
      high-dose well-nourished chronic alcohol consumers and 12 nonalcoholic controls.
      Alcohol consumption, evaluation of muscle strength by myometry, and deltoid
      muscle biopsy with immunohistochemical and morphometric analysis were performed.
      Apoptosis was assessed by TUNEL, BAX, and BCL-2 immunohistochemical assays.
      Chronic alcoholics compared with controls showed a significantly higher apoptotic
      index in TUNEL (2.35% +/- 0.25% versus 0.18% +/- 0.03%, P < 0.001), BAX (9.16% +/
      2.00% versus 0.66% +/- 0.22%, P < 0.001), and BCL-2 muscle assays (8.08% +/-
      0.20% versus 0.83% +/- 0.20%, P = 0.001), respectively. In addition, these
      apoptotic indexes were higher in alcoholics with skeletal myopathy compared with
      in those without skeletal myopathy (3.04% +/- 0.36% versus 1.65% +/- 0.26%, P =
      0.004 for TUNEL; 17.00% +/- 2.78% versus 1.33% +/- 0.22%, P < 0.001 for BAX; and
      15.13% +/- 3.2% versus 1.03% +/- 0.33%, P < 0.001 for BCL-2 assays,
      respectively). We conclude that apoptosis is present in the skeletal muscle of
      high-dose alcohol consumers, mainly in those affected by myopathy. However, the
      specific pathogenic mechanism of apoptosis in chronic skeletal myopathy in
      alcoholics remains to be elucidated.

PMID- 14691910
TI  - Expression of matrix metalloproteinases 2 and 7 in tumor cells correlates with
      the World Health Organization classification subtype and clinical stage of thymic
      epithelial tumors.
AB  - To investigate the roles of matrix metalloproteinases (MMPs) in thymic epithelial
      tumors, we examined the expression of MMP-2, -7, and -9; membrane-type 1 (MT1)
      MMP; and tissue inhibitor of metalloproteinase-2 (TIMP-2) in 57 tumors by
      immunohistochemistry and in selected 15 cases by in situ hybridization. The
      tumors consisted of 5 type A, 12 type AB, 11 type B1, 11 type B2, 9 type B3, and
      9 type C thymomas according to the World Health Organization histologic
      classification system and of 22 stage I, 13 stage II, 8 stage III, and 14 stage
      IV thymomas according to the Masaoka staging system. In the positive cases, MMPs
      and TIMP-2 were expressed in both tumor cells and stromal cells. The cellular
      localization of MMPs detected by immunohistochemistry was almost identical with
      that of the mRNA signals detected by in situ hybridization. MMP-2 and MMP-7 were
      predominantly expressed in type B3 thymoma and type C thymoma, respectively.
      Expression of MT1-MMP and TIMP-2 correlated with that of MMP-2, indicating a
      proteolytic activation of the latter. MMP-9 was prominent in type B2 thymoma.
      Expression in tumor cells of MMP-2 or MMP-7 was also correlated with clinical
      stage. The present study suggests that certain MMPs may play an important role in
      the tumor progression of different subtypes of thymic epithelial tumors and that
      MMP-2 and MMP-7 may contribute to the tumor aggressiveness and malignant
      potential.

PMID- 14691911
TI  - Telomerase activity and proliferation index in aggressive mature B-cell lymphoma:
      comparison to germinal center phenotypic markers.
AB  - Cell proliferation may be evaluated by various methods, including Ki-67
      immunohistochemistry and measures of telomerase activity. Both methods would
      theoretically show comparable increases in a given case. To evaluate the
      relationship between these 2 markers of proliferation in aggressive mature B-cell
      lymphomas, 48 cases were studied. The study group included 5 cases of mantle cell
      lymphoma (MCL); 6 cases of Burkitt's/Burkitt's-like lymphoma (BL); 9 cases of
      follicular lymphoma, grade 3 (FLC); and 28 cases of diffuse large B-cell lymphoma
      (DLC). Telomerase activity was measured as total product generated (TPG) units,
      and TPG results for the aforementioned cases were compared to the TPG results for
      10 cases of reactive follicular hyperplasia. An overlap in TPG scores between
      reactive cases and lymphoma cases was found. Significant differences in both log
      TPG (P = 0.0443) and Ki-67 (P = 0.0006) were seen in the different lymphoma
      types. A positive correlation between Ki-67 percentage and TPG score was
      identified in FLC (r = 0.9281; P = 0.0003), but a poor correlation between these
      2 indicators was seen in the other lymphoma types. Cluster analysis identified
      distinct patterns for MCL, FLC, and BL, but heterogeneous patterns for DLC.
      Because increases in both Ki-67 proliferation and telomerase activity are
      reported in normal germinal centers (GCs), these tests were also evaluated for
      usefulness as markers of a GC cell phenotype. Among the FLC and DLC cases,
      features of a GC phenotype significantly correlated with increased Ki-67
      percentage (P = 0.0152), but not with increased log TPG. An elevated log TPG
      correlated with CD10 expression, and elevated Ki-67 percentage correlated with
      both CD10 and BCL-6 expression. TPG level and Ki-67 percentage did not correlate
      with the presence of t(14;18) or BCL-2 protein expression. Although the
      proliferation patterns were fairly distinctive for MCL, FLC, and BL, these
      studies show that markers of cell proliferation do not by themselves,identify
      distinct subtypes of large cell lymphomas. With the exception of FLC, the tumors
      exhibited poor correlation between telomerase activity and Ki-67 proliferation
      index. These tests did show some correlation with expression of GC cell
      phenotypic markers, however.

PMID- 14691912
TI  - The contribution of placental oxidative stress to early pregnancy failure.
AB  - In cases of miscarriage, onset of the maternal blood flow to the placenta is
      precocious and disorganized compared with this event in normal pregnancy. We
      sought to determine whether this difference is associated with excessive levels
      of oxidative damage and stress in the placental tissues. Morphological and
      immunohistochemical markers of cellular stress and damage, including expression
      of heat shock protein 70, formation of N-Tyr residues, and lipid peroxidation,
      were increased in tissues obtained from missed miscarriages compared with
      controls. The effect was greatest in those pregnancies of shorter than 77 days'
      duration and with evidence of recent fetal demise. It was associated with
      increased apoptosis and decreased numbers of mitotic cells, indicating that
      oxidative stress overwhelms cellular antioxidant defense systems. No differences
      were observed between miscarriages with normal and abnormal karyotypes. The
      spectrum of villous changes occurring after fetal demise indicates that the
      duration of placental retention in utero after fetal demise is a critical
      determinant of villous histology. The causes of many miscarriages remain unclear;
      however, our findings indicate that placental oxidative stress with resultant
      damage to the syncytiotrophoblast, secondary to early onset of the maternal
      circulation, may provide a final common mechanism.

PMID- 14691913
TI  - Abnormal expression of pRb, p16, and cyclin D1 in gastric adenocarcinoma and its
      lymph node metastases: relationship with pathological features and survival.
AB  - The retinoblastoma (Rb) pathway controls the G1-S checkpoint of the cell cycle.
      Inactivating mutations and deletions of p16 and Rb and up-regulation of cyclin D1
      disrupt this pathway and occur in many cancers. However, the concurrent
      expression of these genes in primary and metastatic gastric cancer is unknown,
      and the prognostic value of their expression is unclear. In this study, the
      expression of cyclin D1, retinoblastoma protein (pRb), and p16 in 67 resected
      gastric adenocarcinomas, and of pRb and p16 in 40 associated lymph node
      metastases, was determined using a streptavidin-biotin-peroxidase
      immunohistochemical method. Relationships with clinical and pathological features
      were analyzed. Cyclin D1 overexpression (>/=5% expression) was seen in 55% of
      cancers; pRb loss (<20% expression), in 33%; p16 loss (<10% expression), in 49%;
      and at least 1 of these abnormalities, in 92.5%. Cyclin D1 overexpression was
      associated with poor differentiation (P = 0.027) and signet ring cell type (P =
      0.029). pRb expression was lower in lymph node metastases than in the
      corresponding primary tumors (P <0.001). Univariate and multivariate survival
      analysis (minimum follow-up 72 months or until death) revealed that <20% pRb
      expression, <30% pRb expression, and International Union Against Cancer stage >2
      were associated with worse overall survival. The results suggest that Rb pathway
      disturbances play an important role in gastric carcinogenesis. The poor prognosis
      of cancers with low pRb expression and the reduced pRb expression in lymph node
      metastases raise the possibility that Rb and related genes also influence
      progression.

PMID- 14691914
TI  - Major histocompatibility complex status in breast carcinogenesis and relationship
      to apoptosis.
AB  - Major histocompatibility complex (MHC) molecules are of central importance in
      regulating the immune response against tumors. In this study we used
      immunohistochemistry to study human leukocyte antigen (HLA) class I and II
      antigen expression in normal breast tissues and benign, preneoplastic, primary,
      and metastatic breast lesions using antibodies against beta-2-microglobulin
      (beta2-m), heavy-chain, and HLA-DR antigens. Whereas all normal tissues and
      benign lesions were positive for beta2-m and HLA-A, -B, and -C antigens, total
      loss of HLA class I antigens was found in 37% (11 of 30) of in situ carcinomas,
      in 43% (56 of 131) of the primary tumors, and in 70% (31 of 45) of the lymph node
      metastases. HLA-DR was also underexpressed in breast cancer cells; thus 20% (6 of
      30) of in situ carcinomas, 15% of invasive carcinomas (20 of 131), and only 1
      metastatic case were positive for this antigen. Both HLA class I and II antigen
      expression were more frequently down-regulated in metastatic lesions than in
      primary breast lesions (P <0.05), and a tendency toward a simultaneous defective
      expression of HLA class I and II antigens was observed in primary carcinomas (P =
      0.07). However, no correlation was found between the expression of any of the
      aforementioned molecules and pathological parameters or survival. Interestingly,
      HLA class I expression was expressed more frequently in tissues with high
      apoptotic activity and was significantly associated with the expression of the
      proapoptotic bax gene (P = 0.02), and was inversely associated with expression of
      the antiapoptotic bcl-2 gene (P = 0.03). We conclude that alterations in HLA
      class I and II antigen expression are early events in breast carcinogenesis and
      play significant roles in metastatic progression. In addition, their expression
      is correlated with apoptosis-regulating proteins, which may influence the
      cytotoxicity of T cells against HLA class I-specific tumor antigens.

PMID- 14691915
TI  - Surgical pathology of pulmonary thromboendarterectomy: a study of 54 cases from
      1990 to 2001.
AB  - Thromboendarterectomy is performed to treat chronic thromboembolic pulmonary
      hypertension with obstruction of main, lobar, or segmental pulmonary arteries.
      The present study evaluated surgical specimens removed between 1990 and 2001.
      Medical histories and microscopic slides were reviewed in each case. Study slides
      were stained with hematoxylin and eosin and Verhoeff-van Gieson and evaluated for
      thrombus, collagen, elastin, atherosclerosis, hemosiderin, calcification, and
      inflammation. The study group comprised 54 patients (30 women and 24 men),
      ranging in age from 33 to 77 years (mean, 58 years). Clinically, 28 (52%) had a
      history of deep leg vein thrombosis and 42 (78%) had a history of pulmonary
      embolism; 24 (44%) had both events. Coagulation abnormalities were documented in
      15 (28%); autoimmune or hematologic disorders, in 8 (15%). Pulmonary
      thromboendarterectomy was bilateral in 52 patients (96%) and right-sided in 2.
      Six patients also had obstructions resected from the main pulmonary arteries.
      Obstruction limited to segmental arteries occurred only in women. Grossly, right
      sided specimens were larger than left-sided ones (P = 0.003). Microscopically,
      ages of thrombi were uniform in 72% and variable in 28%. Intima was thickened in
      all patients and consisted of collagen (100%), elastin (67%), hemosiderin (56%),
      inflammation (53%), atherosclerosis (32%), and calcification (15%). We determined
      that pulmonary thromboendarterectomy was performed most often in middle-aged and
      elderly patients with a history of deep venous thrombosis or pulmonary embolism.
      Less than 50% of the patients had an identifiable coagulation, autoimmune, or
      hematologic abnormality. Most patients had bilateral disease and resections.
      Right-sided specimens were significantly larger than left-sided specimens, and
      lower lobe involvement was more common than involvement elsewhere. Resected
      tissues most commonly exhibited old organized thrombus.

PMID- 14691916
TI  - Secretory carcinoma of the breast: a distinct variant of invasive ductal
      carcinoma assessed by comparative genomic hybridization and immunohistochemistry.
AB  - Secretory carcinomas (SCA) are distinguished from infiltrating ductal carcinomas
      (IDC) of the breast by their characteristic histomorphology and more favorable
      prognosis and by the expression of a chimeric tyrosine kinase that is encoded by
      the ETV6-NTRK3 fusion gene. On this basis, we evaluated 13 SCAs (12 of them with
      ETV6-NTRK3 gene fusion) by molecular and immunohistochemical (IHC) methods. DNA
      was obtained from 8 of 13 microdissected SCAs and was analyzed for genetic
      alterations (GA) by comparative genomic hybridization (CGH). IHC staining was
      performed for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and
      Ki-67 (MIB1) in all 13 cases. Molecular and immunohistochemical results in SCAs
      were compared with previous data regarding immunohistochemical and molecular
      characteristics of IDCs. An average of 2.0 GAs (range: 0 to 6) were detected,
      including recurrent gains of chromosome 8q (37.5%) and 1q (25%) and losses of 22q
      (25%). Four of 13 (31%) SCAs were positive for ER, and 2 were positive for PR.
      The mean MIB1-labeling index was 11.4% (range: <1 to 34%). Her-2/neu protein
      overexpression was detected in 2 cases, including 1 with strong (score 3+) and 1
      with weak HER2/neu expression (score 2+). Fluorescence in situ hybridization
      analysis of the latter case showed no evidence of HER-2/neu-gene amplification.
      Compared with previous findings in IDCs, SCAs are characterized by a relatively
      low number of GAs, a low proliferative rate, infrequent HER2/neu protein
      overexpression, decreased steroid hormone receptor expression, and expression of
      ETV6-NTRK3 fusion gene. These results support the hypothesis that SCAs have
      immunohistochemical and genetic features that distinguish them from IDCs of the
      usual type.

PMID- 14691917
TI  - KIT 1530ins6 mutation defines a subset of predominantly malignant
      gastrointestinal stromal tumors of intestinal origin.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. GISTs express KIT and show gain-of-function KIT
      mutations. Most of these mutations affect the KIT juxtamembrane domain, but other
      KIT domains are mutated at a lower frequency. In this study, frequency of GCC TAT
      insertion mutation (1530ins6) in KIT exon 9 (extracellular domain) and its
      possible clinicopathologic significance was investigated. Screening of 520 GISTs
      identified 26 cases with 1530ins6 KIT mutation and confirmed the previously
      reported low frequency of this type of KIT mutation among GISTs of different
      locations. Of the 26 tumors with 1530ins6 KIT mutation studied, 21 originated
      from the small intestine, 1 from the colon, and 3 from the rectum. In 1 case,
      primary small intestinal versus colonic localization could not be clearly
      established because of intra-abdominal dissemination. No distinctive
      morphological features were identified for the cohort of tumors defined by
      1530ins6 KIT mutations. Most of the tumors showed predominant spindle cell
      morphology, and a few cases had epithelioid or pleomorphic histological features.
      Following previously published criteria based on tumor size and mitotic rate, 22
      of 26 (85%) tumors were classified as malignant or potentially malignant, and 4
      (15%) were classified as probably benign. A malignant clinical course was
      documented in 18 of 19 tumors from the malignant category. The survival times of
      11 patients who died of disseminated GISTs ranged from 1 month to 105 months
      (median survival time, 26 months). In contrast, 2 of 4 GISTs assigned as probably
      benign tumors with follow-up information had long disease-free survival. GISTs
      carrying 1530ins6 occur exclusively in the intestinal location, and a great
      majority of these tumors follow a malignant course.

PMID- 14691918
TI  - Frequent mutation reversion inversely correlates with clinical severity in a
      genetic liver disease, hereditary tyrosinemia.
AB  - Hereditary tyrosinemia type I (HTI), a severe disease affecting primarily the
      liver, is caused by a deficiency of fumarylacetoacetate hydrolase (FAH). HTI is
      clinically heterogeneous, with no correlation between genotype and phenotype.
      Reversion of FAH mutant alleles in livers of HTI patients was reported
      previously, but the clinical significance of this phenomenon has not been fully
      documented. In the present study, the mosaic expression of FAH was analyzed by
      immune cytochemistry in liver specimens from a cohort of 26 French-Canadian HTI
      patients who underwent liver transplantation and related to the histopathologic
      status of the liver and the clinical history. Reversion was observed in 88% of
      patients with reverted surfaces ranging from 0.1% to 85%. Patients with the
      chronic form had a much higher surface of reversion (average, 36%) than those
      with the acute form (average, 1.6%) and a lower incidence of liver dysplasia.
      Within reverted nodules, hepatocytes had a normal appearance and showed no
      dysplasia. Hepatocellular carcinoma was observed only in FAH-negative regions. In
      summary, the extent of mutation reversion of the FAH gene in the liver of HTI
      patients was inversely correlated with the clinical severity of the disease,
      suggesting that the corrected hepatocytes play a substantial protective role in
      liver function.

PMID- 14691919
TI  - Intraepidermal cells of Paget's carcinoma of the breast can be genetically
      different from those of the underlying carcinoma.
AB  - Paget's carcinoma (PC) of the breast is characterized by neoplastic cells of
      "glandular" type located within the epidermis of the nipple-areolar complex,
      often associated with an underlying ductal carcinoma, either in situ or invasive.
      At present the origin of PC cells is controversial, although there is a
      widespread opinion that PC cells are "foreign" elements to the epidermis
      resulting from an epidermotropic migration of neoplastic elements from an
      underlying ductal carcinoma. An alternative view is that some cases result from
      neoplastic transformation of preexisting, innocent intraepidermal clear cells of
      the nipple-areolar complex (Toker cells) that migrate from nonneoplastic ducts.
      Consequently, 10 cases were studied using methods for clonality (ie, loss of
      heterozygosity and mitochondrial DNA displacement loop sequence analysis).
      Microdissection of intraepidermal neoplastic cells and of cells from underlying
      duct carcinomas and metastases was performed. In no fewer than 2 cases, PC cells
      were genetically different from underlying lesions, which showed consistent
      homology among themselves. Therefore, it is suggested that the rule of
      epidermotropism by neoplastic cells from an underlying carcinoma is not
      applicable to all cases, and that in some cases PC cells might be the result of
      neoplastic transformation of preexisting intraepidermal nonneoplastic cells.
      Consequently, the underlying tumors are coincidental neoplastic lesions
      (collision tumors).

PMID- 14691920
TI  - Human cytomegalovirus infection of the gastrointestinal tract in apparently
      immunocompetent patients.
AB  - Human cytomegalovirus (HCMV) infection is usually reported in immunocompromised
      patients. This study reports 11 cases of HCMV infection of the gastrointestinal
      (GI) tract diagnosed in apparently immunocompetent hosts. The median age of the
      patients studied was 76 years, and the major presenting symptoms were diarrhea,
      epigastric pain, and abdominal discomfort. The large intestine was involved in 6
      cases, the stomach in 4 cases, and the lower esophagus in 1 case. Endoscopy
      revealed ulcers or hypertrophic folds in the GI tract and single ulcers or
      erosions in the colon and rectum. Light microscopy showed chronic inflammatory
      infiltrate in the lamina propria in all cases. The diagnosis of HCMV infection
      was based on the histological and immunohistochemical identification of HCMV
      inclusion bodies in different cell types, including epithelial, endothelial,
      stromal, and smooth muscle cells. Both "classical" inclusions, characterized by
      an "owl's eye" appearance, and atypical inclusions were found. For all patients,
      no apparent causes of immunodeficiency were detected at the time of diagnosis of
      HCMV infection. At follow-up, however, 4 patients were found to harbor a
      malignant tumor (ie, pancreas, lung, Vater's papilla, and extrahepatic bile duct)
      at an interval of 2 to 5 months after the diagnosis of HCMV infection. Especially
      in elderly patients, HCMV infection of the GI tract might be an early clue to the
      presence of immunologic defects induced by an underlying neoplasia.

PMID- 14691921
TI  - Intrahepatic cholangiocarcinoma in cirrhosis presents granulocyte and granulocyte
      macrophage colony-stimulating factor.
AB  - Intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular and
      cholangiocarcinoma (HC-CC) are known to arise occasionally in hepatitis-related
      cirrhosis, although their clinicopathological features remain unclarified. In
      this study, we characterized the ICC (9 cases) and ICC elements of HC-CC (11
      cases) arising in nonbiliary cirrhosis. Thirty-three hepatocellular carcinomas
      (HCC) associated with nonbiliary cirrhosis and 24 ICC without cirrhosis were used
      as controls. Prominent neutrophilic infiltration was frequent in ICC with
      cirrhosis (78%) and ICC elements of combined HC-CC (72%). Neutrophilic
      infiltration-related cytokines (interleukin 8, granulocyte colony-stimulating
      factor [G-CSF], and granulocyte macrophage colony-stimulating factor [GM-CSF])
      were expressed frequently and intensely in carcinoma cells of ICC with cirrhosis
      (40%, 80%, and 60%, respectively) and in ICC elements of the combined one (13%,
      38%, and 63%, respectively). Interleukin 8 was expressed in 18% of ICC without
      cirrhosis, irrespective of neutrophilic infiltration. Neutrophilic infiltration
      and expression of G-CSF and GM-CSF were in parallel (P < 0.05). G-CSF and GM-CSF
      mRNA were detected by RT-PCR in tissue specimens expressing G-CSF and GM-CSF at
      the protein level. Such neutrophilic infiltration and expression of G-CSF and GM
      CSF were not evident in controls. The expressions of c-kit and c-Met, as a
      hematopoietic and hepatic stem cell marker, were seen frequently in ICC with
      cirrhosis (80% and 80%, respectively) and ICC elements of the combined one (63%
      and 50%, respectively). The present study revealed that the frequent expression
      of G-CSF and GM-CSF is a characteristic of ICC with cirrhosis and ICC in combined
      carcinoma, probably representing a phenotype of fetal hepatic parenchymal cell.
      The expression of these cytokines may be causally related to prominent
      neutrophilic infiltration.

PMID- 14691922
TI  - Genotypic analysis of pulmonary Langerhans cell histiocytosis.
AB  - Reported studies show that the systemic form of Langerhans cell histiocytosis
      (LCH) is a clonal expansion of Langerhans cells (LC) associated with aberrant
      expression of several oncogenes or tumor-suppressor genes. LCH of the lung is a
      heterogenous group of lesions thought to be a reactive rather than neoplastic
      process. The histogenesis of the LCH of the lung is uncertain, and to date there
      are no studies investigating its underlying molecular abnormalities. We performed
      comparative genotypic analysis by using allelic loss (LOH) of polymorphic
      microsatellite markers associated with tumor suppressor genes. Fourteen cases of
      formalin-fixed, paraffin-embedded LCH of the lung were studied. Microdissection
      of a total of 26 nodules from 14 patients and paired reference lung tissue was
      performed under stereomicroscopic visualization. To evaluate allelic loss, we
      used a panel of 11 polymorphic microsatellite markers that were situated at or
      near tumor suppressor genes on chromosomes 1p, 1q, 3p, 5p, 9p, 17p, and 22q. The
      PCR products were analyzed by using capillary electrophoresis to identify
      germline heterozygous alleles and LOH. Allelic loss at 1 or more tumor suppressor
      gene loci was identified in 19 of 24 nodules. The total fractional allelic loss
      (FAL) ranged from 6% (1q) to 41% (22q), with a mean of 22%. The FAL in individual
      cases ranged from 0 (7 nodules) to 57% (1 nodule). Fifteen discordant allelic
      losses at 1 to 3 chromosomal loci were identified in 8 patients with multiple
      synchronous nodules. Our results show that LOH of tumor suppressor genes is
      present in the LCH of the lung, and they indicate that the putative tumor
      suppressor genes situated on chromosomes 9p and 22q may play a role in the
      development of a subset of the LCH of the lung.

PMID- 14691923
TI  - Unusual IgM fibrillar deposits in glomerulonephritis: ultrastructural and
      diffraction studies in a case report.
AB  - Morphological examination of 2 renal biopsy specimens obtained from a 69-year-old
      woman with a nephrotic syndrome, high blood pressure, and a reduced glomerular
      filtration rate revealed, in ultrastructural study, a type of a
      glomerulonephritis with fibrillar deposits in a subendothelial position which
      were unusual in their immunoglobulin components (mainly IgM). The fibrillar
      components were of irregular size, 13 to 18 nm in diameter and presented a very
      particular "barbed wire" morphological aspect, not hitherto described.
      Diffraction studies and image analysis, revealed spiraled fibrils with regular
      alternating elements that we suggest may correspond to IgM molecules. The
      clinical (isolated renal symptoms) and laboratory (traces of 3 monoclonal
      components in the serum and 2 normal bone marrow biopsy specimens) data provided
      no evidence of hematopoietic malignancy, viral hepatitis or cryoglobulinemia.

PMID- 14691924
TI  - Osteosarcoma in a patient with McCune-Albright syndrome and Mazabraud's syndrome:
      a case report emphasizing the cytological and cytogenetic findings.
AB  - Osteosarcomatous transformation in fibrous dysplasia is unusual. The incidence is
      increased in patients with concomitant Mazabraud's syndrome and McCune-Albright
      syndrome. We report the cytological, histological, and cytogenetic findings of
      this rare entity arising from a mass in the right elbow of a 44-year-old African
      American woman. The fine-needle aspiration (FNA) findings were diagnostic of
      malignancy, with markedly atypical spindle and polygonal cells admixed with
      osteoid. The diagnosis of osteosarcoma by FNA was subsequently further confirmed
      by histological evaluation of an above-elbow amputation specimen. Fluorescence in
      situ hybridization and comparative genomic hybridization demonstrated trisomies
      of chromosomes 5 and 7 in the fibrous dysplasia and osteosarcoma. In addition,
      multiple chromosomal abnormalities were also noted in the osteosarcoma. We are
      unaware of any previous reports of the cytogenetic findings in the tissue of this
      rare condition, and argue for the value of FNA in the evaluation of such patients
      under selected conditions.

PMID- 14691926
TI  - Chloroquine-induced phospholipidosis of the kidney mimicking Fabry's disease.

PMID- 14691935
TI  - Hydration dependence of backbone and side chain polylysine dynamics: a 13C solid
      state NMR and IR spectroscopy study.
AB  - The molecular dynamics of solid poly-L-lysine has been studied by the following
      natural abundance (13)C-NMR relaxation methods: measurements of the relaxation
      times T(1) at two resonance frequencies, off-resonance T(1rho) at two spin-lock
      frequencies, and proton-decoupled T(1rho). Experiments were performed at
      different temperatures and hydration levels (up to 17% H(2)O by weight). The
      natural abundance (13)C-CPMAS spectrum of polylysine provides spectral resolution
      of all types of backbone and side chain carbons and thus, dynamic parameters
      could be determined separately for each of them. At the same time, the
      conformational properties of polylysine were investigated by Fourier transform
      infrared spectroscopy. The data obtained from the different NMR experiments were
      simultaneously analyzed using the correlation function formalism and model-free
      approach. The results indicate that in dry polylysine both backbone and side
      chains take part in two low amplitude motions with correlation times of the order
      of 10(-4) s and 10(-9) s. Upon hydration, the dynamic parameters of the backbone
      remain almost constant except for the amplitude of the slower process that
      increases moderately. The side chain dynamics reveals a much stronger hydration
      response: the amplitudes of both slow and fast motions increase significantly and
      the correlation time of the slow motion shortens by about five orders of
      magnitude, and at hydration levels of more than 10% H(2)O fast and slow side
      chain motions are experimentally indistinguishable. These changes in the
      molecular dynamics cannot be ascribed to any hydration-dependent conformational
      transitions of polylysine because IR spectra reveal almost no hydration
      dependence in either backbone or side chain absorption domains. The physical
      nature of the fast and slow motions, their correlation time distributions, and
      hydration dependence of microdynamic parameters are discussed.

PMID- 14691936
TI  - Statistical correlation between protein secondary structure and messenger RNA
      stem-loop structure.
AB  - A new integrated sequence-structure database, called IADE (Integrated ASTRAL-DSSP
      EMBL), incorporating matching mRNA sequence, amino acid sequence, and protein
      secondary structural data, is constructed. It includes 648 protein domains. Based
      on the IADE database, we studied the relation between RNA stem-loop frequencies
      and protein secondary structure. It was found that the alpha-helices and beta
      strands on proteins tend to be preferably "coded" by mRNA stem region, while the
      coils on proteins tend to be preferably "coded" by mRNA loop region. These
      tendencies are more obvious if we observe the structural words (SWs). An SW is
      defined by a four-amino-acid-fragment that shows the pronounced secondary
      structural (alpha-helix or beta-strand) propensity. It is demonstrated that the
      deduced correlation between protein and mRNA structure can hardly be explained as
      the stochastic fluctuation effect.

PMID- 14691937
TI  - Synthesis, stability, and protonation studies of a self-complementary dodecamer
      containing the modified nucleoside 2'-deoxyzebularine.
AB  - The nucleoside 2'-deoxyzebularine (K) was incorporated into the self
      complementary dodecamer 5'-CGTACGKGTACG-3' by solid-phase 2
      cyanoethylphosphoramidite chemistry using dimethoxytrityl (DMT) as the 5'
      hydroxyl protecting group. Standard synthesis cycles using trichloroacetic acid
      and short ammonia treatment (50 degrees C for 30 min) were found to be the
      optimal conditions to obtain the desired dodecamer with minimum acid and basic
      degradation of the acid- and base-sensitive 2-pyrimidinone residue. The
      protonation equilibria of the K nucleoside and of the dodecamer at 37 degrees C
      were studied by means of spectroscopically monitored titrations. For the K
      nucleoside, a pK(a) value of 3.13 +/- 0.09 was obtained. For the dodecamer, four
      acid-base species were found in the pH range 2-12, with pK(a) values of 9.60 +/-
      0.07, 4.46 +/- 0.16, and 2.87 +/- 0.19. Melting experiments were carried out to
      confirm the proposed acid-base concentration profiles. Finally, kinetic
      experiments were also carried out at several pH values to evaluate the stability
      of the K nucleoside and of the dodecamer. An increased stability was shown by the
      K nucleoside when incorporated into the dodecamer. Multivariate methods based on
      both hard- and soft-modeling were applied for the analysis of spectroscopic data,
      allowing the estimation of concentration profiles and pure spectra.

PMID- 14691938
TI  - Gelation behaviors of schizophyllan-sorbitol aqueous solutions.
AB  - On addition of D-sorbitol, schizophyllan (SPG) aqueous solution forms a
      thermoreversible gel upon cooling. The gelation process is characterized by
      rheology, differential scanning calorimetry (DSC), and optical rotation
      measurement (ORD). It is found that the Winter-Chambon criterion works well in
      determining the critical gelation point of the present system, although the
      criterion has been scarcely applicable to systems that show weak-gel properties
      even before gelation. Moreover, ORD and DSC results indicate that a disordered to
      ordered conformational change accompanies the gelation process, which is
      attributed to the transition from SPG triple helix II to I. The gelation
      temperature of SPG-sorbitol aqueous solution is almost independent of SPG
      concentration in the examined concentration range and is slightly decreased by
      lowering SPG molecular weight, while greatly influenced by sorbitol content. The
      gelation is considered to be induced by the transition from SPG triple helix II
      to I, which leads to a three-dimensional network constituted by the extremely
      entangled and stiff SPG triple helices I. Furthermore, it is proved that neither
      junction zone nor aggregation of SPG triple helices is involved in the SPG
      sorbitol gels. The SPG-sorbitol gel is structurally like a solution that is
      unable to flow within a timescale of usual observation.

PMID- 14691939
TI  - Chitosan hollow fiber membranes.
AB  - Chitosan hollow fibers were produced by wet spinning, taking advantage of the
      unique rheological properties of highly viscous chitosan solutions in acetic
      acid. The mechanical and separation properties of hollow fibers were tested. The
      mechanical properties were determined by measuring tensile force, tensile stress,
      elongation, and initial elasticity module. The separation properties were
      specified by determining retention coefficients of particular blood components
      and determining cut-off of the membrane by the analysis of dextran molecular
      weight distribution in the feed and permeate using a technique of gel
      chromatography (GPC)-Shimadzu gel chromatograph.

PMID- 14691940
TI  - Mechanism of catalytic RNA.

PMID- 14691941
TI  - The hairpin ribozyme.
AB  - The hairpin ribozyme is a naturally occurring RNA that catalyzes sequence
      specific cleavage and ligation of RNA. It has been the subject of extensive
      biochemical and structural studies, perhaps the most detailed for any catalytic
      RNA to date. Comparison of the structures of its constituent domains free and
      fully assembled demonstrates that the RNA undergoes extensive structural
      rearrangement. This rearrangement results in a distortion of the substrate RNA
      that primes it for cleavage. This ribozyme is known to achieve catalysis
      employing exclusively RNA functional groups. Metal ions or other catalytic
      cofactors are not used. Current experimental evidence points to a combination of
      at least four mechanistic strategies by this RNA: (1) precise substrate
      orientation, (2) preferential transition state binding, (3) electrostatic
      catalysis, and (4) general acid base catalysis.

PMID- 14691942
TI  - Roles of protein subunits in RNA-protein complexes: lessons from ribonuclease P.
AB  - Ribonucleoproteins (RNP) are involved in many essential processes in life.
      However, the roles of RNA and protein subunits in an RNP complex are often hard
      to dissect. In many RNP complexes, including the ribosome and the Group II
      introns, one main function of the protein subunits is to facilitate RNA folding.
      However, in other systems, the protein subunits may perform additional functions,
      and can affect the biological activities of the RNP complexes. In this review, we
      use ribonuclease P (RNase P) as an example to illustrate how the protein subunit
      of this RNP affects different aspects of catalysis. RNase P plays an essential
      role in the processing of the precursor to transfer RNA (pre-tRNA) and is found
      in all three domains of life. While every cell has an RNase P (ribonuclease P)
      enzyme, only the bacterial and some of the archaeal RNase P RNAs (RNA component
      of RNase P) are active in vitro in the absence of the RNase P protein. RNase P is
      a remarkable enzyme in the fact that it has a conserved catalytic core composed
      of RNA around which a diverse array of protein(s) interact to create the RNase P
      holoenzyme. This combination of highly conserved RNA and altered protein
      components is a puzzle that allows the dissection of the functional roles of
      protein subunits in these RNP complexes.

PMID- 14691943
TI  - Catalytic roles for proton transfer and protonation in ribozymes.
AB  - Utilization of proton transfer in catalysis, which is well known in the
      mechanisms of protein enzymes, has been described only relatively recently for
      RNA enzymes. In this article, we present a current understanding of proton
      transfer by nucleic acids. Rate enhancement and specificity conferred by general
      acid-base catalysis are discussed. We also present possibilities for
      electrostatic catalysis from general acids and bases as well as cationic base
      pairs. The microenvironments of a large RNA provide the possibility of histidine
      like pK(a)s for proton transfer, as well as lysine- and arginine-like pK(a)s for
      electrostatic catalysis. Discussion on proton transfer focuses on the hepatitis
      delta virus (HDV) and hairpin ribozymes, with select examples drawn from the
      protein literature. Discussion on electrostatic catalysis also draws on these two
      ribozymes, and a postulate for electrostatic catalysis by a cationic base pair in
      the mechanism of peptidyl transfer in the ribosome is presented. We also provide
      a perspective on possibilities for phosphoryl transfer mechanisms involving
      phosphorane intermediates and unusual tautomeric forms of the bases. Lastly, a
      distinction is made between ground state and "transition state" pK(a)s. We favor
      a model in which changes in pH lead to changes in the distribution of reactive
      and nonreactive ionizations of the ribozyme molecules in the ground state, and
      therefore suggest that "pK(a) changes in the transition state" do not provide an
      acceptable explanation for observed pH-rate profiles.

PMID- 14691944
TI  - Understanding the transition states of phosphodiester bond cleavage: insights
      from heavy atom isotope effects.
AB  - The nucleotides of DNA and RNA are joined by phosphodiester linkages whose
      synthesis and hydrolysis are catalyzed by numerous essential enzymes. Two
      prominent mechanisms have been proposed for RNA and protein enzyme catalyzed
      cleavage of phosphodiester bonds in RNA: (a) intramolecular nucleophilic attack
      by the 2'-hydroxyl group adjacent to the reactive phosphate; and (b)
      intermolecular nucleophilic attack by hydroxide, or other oxyanion. The general
      features of these two mechanisms have been established by physical organic
      chemical analyses; however, a more detailed understanding of the transition
      states of these reactions is emerging from recent kinetic isotope effect (KIE)
      studies. The recent data show interesting differences between the chemical
      mechanisms and transition state structures of the inter- and intramolecular
      reactions, as well as provide information on the impact of metal ion, acid, and
      base catalysis on these mechanisms. Importantly, recent nonenzymatic model
      studies show that interactions with divalent metal ions, an important feature of
      many phosphodiesterase active sites, can influence both the mechanism and
      transition state structure of nonenzymatic phosphodiester cleavage. Such detailed
      investigations are important because they mimic catalytic strategies employed by
      both RNA and protein phosphodiesterases, and so set the stage for explorations of
      enzyme-catalyzed transition states. Application of KIE analyses for this class of
      enzymes is just beginning, and several important technical challenges remain to
      be overcome. Nonetheless, such studies hold great promise since they will provide
      novel insights into the role of metal ions and other active site interactions.

PMID- 14691945
TI  - Mechanistic studies on acyl-transferase ribozymes and beyond.
AB  - In vitro selection has allowed the isolation of many new ribozymes that are able
      to catalyze an ever-widening array of chemical transformations. Mechanistic
      studies on these selected ribozymes have provided valuable insight into the
      methods that RNA can invoke to overcome different catalytic tasks. We focus on
      the methods employed in these mechanistic studies using the acyl-transferase
      family of selected ribozymes as well-studied reference systems. Chemical and
      biochemical techniques have been used in tandem in order to draw conclusions on
      the various modes of catalysis employed by the different family members. In turn,
      this type of mechanistic information may provide a means for the redesign and
      optimization of existing ribozymes or the basis for new selection systems for
      more powerful RNA catalysts.

PMID- 14691946
TI  - New approaches to targeting RNA with oligonucleotides: inhibition of group I
      intron self-splicing.
AB  - RNA is one class of relatively unexplored drug targets. Since RNAs play a myriad
      of essential roles, it is likely that new drugs can be developed that target RNA.
      There are several factors that make targeting RNA particularly attractive. First,
      the amount of information about the roles of RNA in essential biological
      processes is currently being expanded. Second, sequence information about
      targetable RNA is pouring out of genome sequencing efforts at unprecedented
      levels. Third, designing and screening potential oligonucleotide therapeutics to
      target RNA is relatively simple. The use of oligonucleotides in cell culture,
      however, presents several challenges such as oligonucleotide uptake and
      stability, and selective targeting of genes of interest. Here, we review
      investigations aimed at targeting RNA with oligonucleotides that can circumvent
      several of these potential problems. The hallmark of the strategies discussed is
      the use of short oligonucleotides, which may have the advantage of higher
      cellular uptake and improved binding selectivity compared to longer
      oligonucleotides. These strategies have been applied to Group I introns from the
      mammalian pathogens Pneumocystis carinii and Candida albicans. Both are examples
      of fungal infections that are increasing in number and prevalence.

PMID- 14691947
TI  - Dephosphorylation of inner arm 1 is associated with ciliary reversals in
      Tetrahymena thermophila.
AB  - In many organisms, depolarizing stimuli cause an increase in intraciliary Ca2+,
      which results in reversal of ciliary beat direction and backward swimming. The
      mechanism by which an increase in intraciliary Ca2+ causes ciliary reversal is
      not known. Here we show that Tetrahymena cells treated with okadaic acid or
      cantharidin to inhibit protein phosphatases do not swim backwards in response to
      depolarizing stimuli. We also show that both okadaic acid and cantharidin inhibit
      backward swimming in reactivated, extracted cell models treated with Ca2+. In
      contrast, treatment of whole cells or extracted cell models with protein kinase
      inhibitors has no effect on backward swimming. These results suggest that a
      component of the axonemal machinery is dephosphorylated during ciliary reversal.
      The phosphorylation state of inner arm dynein 1 (I1) was determined before and
      after cells were exposed to depolarizing conditions that induce ciliary reversal.
      An I1 intermediate chain is phosphorylated in forward swimming cells but is
      dephosphorylated in cells treated with a depolarizing stimulus. Our results
      suggest that dephosphorylation of Tetrahymena inner arm dynein 1 may be an
      essential part of the mechanism of ciliary reversal in response to increased
      intraciliary Ca2+.

PMID- 14691948
TI  - Overexpression of profilin reduces the migration of invasive breast cancer cells.
AB  - The exact role profilin plays in cell migration is not clear. In this study, we
      have evaluated the effect of overexpression of profilin on the migration of
      breast cancer cells. Overexpression was carried out by stably expressing GFP
      profilin in BT474 cells. It was observed that even a moderate level of
      overexpression of profilin significantly impaired the ability of BT474 cells to
      spread on fibronectin-coated substrate and migrate in response to EGF. GFP
      profilin expressing cells also showed increased resistance to detachment in
      response to trypsin and increased tyrosine phosphorylation of focal adhesion
      kinase (FAK) and paxillin compared to the parental and GFP-expressing (control)
      cell lines. These results suggest that perturbation of profilin levels may offer
      a good strategy for controlling the metastatic potential of breast cancer cells.

PMID- 14691949
TI  - The betaII isotype of tubulin is present in the cell nuclei of a variety of
      cancers.
AB  - Tubulin, the subunit protein of microtubules, has generally been thought to be
      exclusively a cytoplasmic protein in higher eukaryotes. We have previously shown
      that cultured rat kidney mesangial cells contain the betaII isotype of tubulin in
      their nuclei in the form of an alphabetaII dimer [Walss et al., 1999: Cell Motil.
      Cytoskeleton 42:274-284, 1999]. More recently, we examined a variety of cancerous
      and non-cancerous cell lines and found betaII in the nuclei of all of the former
      and only a few of the latter (Walss-Bass et al., 2002: Cell Tissue Res. 308:215
      223]. In order to determine if betaII-tubulin occurs in the nuclei of actual
      cancers as well as in cancer cell lines, we used the immunoperoxidase method to
      look for nuclear betaII in a variety of tumors excised from 201 patients. We
      found that 75% of these tumors contain betaII in their nuclei. Distribution of
      nuclear betaII was highly dependent on the type of cancer, with 100% of the colon
      and prostate cancers, but only 19% of the skin tumors, having nuclear betaII.
      Nuclear betaII was particularly marked in tumors of epithelial origin, of which
      83% showed nuclear betaII, in contrast to 54% in tumors of non-epithelial origin.
      In many cases, betaII staining occurred very strongly in the nuclei and not in
      the cytoplasm; in other cases, betaII was present in both. In many cases,
      particularly metastases, otherwise normal cells adjacent to the tumor also showed
      nuclear betaII, suggesting that cancer cells may influence nearby cells to
      synthesize betaII and localize it to their nuclei. Our results have implications
      for the diagnosis, biology, and chemotherapy of cancer.

PMID- 14691950
TI  - Myosin-mediated cytoskeleton contraction and Rho GTPases regulate laminin-5
      matrix assembly.
AB  - Laminin-5 is a major structural element of epithelial tissue basement membranes.
      In the matrix of cultured epithelial cells, laminin-5 is arranged into intricate
      patterns. Here we tested a hypothesis that myosin II-mediated actin contraction
      is necessary for the proper assembly of a laminin-5 matrix by cultured SCC12
      epithelial cells. To do so, the cells were treated with ML-7, a myosin II light
      chain kinase inhibitor, or Y-27632, an inhibitor of Rho-kinase (ROCK), both of
      which block actomyosin contraction. Under these conditions, laminin-5 shows an
      aberrant localization in dense patches at the cell periphery. Since ROCK activity
      is regulated by the small GTPase Rho, this suggests that members of the Rho
      family of GTPases may also be important for laminin-5 matrix assembly by SCC12
      cells. We confirmed this hypothesis since SCC12 cells expressing mutant proteins
      that inhibit RhoA, Rac, and Cdc42 assemble the same aberrant laminin-5 protein
      arrays as drug-treated cells. We have also evaluated the organization of the
      laminin-5 receptors alpha3beta1 and alpha6beta4 integrin and hemidesmosome
      proteins in ML-7- and Y-27632-treated cells or in cells in which RhoA, Rac, and
      Cdc42 activity were inhibited. In all instances, alpha3beta1 and alpha6beta4
      integrin heterodimers, as well as hemidesmosome proteins, localize precisely with
      laminin-5 in the matrix of the cells. In summary, our results provide evidence
      that myosin II-mediated actin contraction and the activity of Rho GTPases are
      necessary for the proper organization of a laminin-5 matrix and localization of
      hemidesmosome protein arrays in epithelial cells.

PMID- 14691951
TI  - Maturation of DC is associated with changes in motile characteristics and
      adherence.
AB  - Migration of dendritic cells (DC) from sentinel sites to lymphoid tissue entails
      the initiation and coordination of a complex series of cytoskeletal
      rearrangements resulting in polarised protrusion, formation of new adhesion
      points, and detachment. Although many diverse receptor-ligand interactions
      stimulating DC maturation and migration have been identified, the changes that
      occur in the structure of the actin cytoskeleton during these processes have
      received little attention. When derived in vitro, immature DC floated in clumps,
      and upon addition of maturation stimuli such as lipopolysaccharide (LPS), they
      rapidly adhered, developed polarity, and assembled actin-rich structures known as
      podosomes at the leading edge of the cell. Podosome assembly was associated with
      the specific recruitment of beta2 integrins, which in the absence of the Wiskott
      Aldrich Syndrome protein (WASp), did not occur. As maturation progressed, normal
      DC once again became rounded and devoid of podosomes. This change in morphology
      was closely associated with a quantitatively reduced ability to adhere to
      fibronectin or ICAM-1-coated surfaces. In immature DC, failure to form podosomes
      or selective inhibition of the CD18 component of podosomes resulted in a
      similarly reduced ability to adhere to ICAM-1, indicating that podosomes, through
      CD18, are necessary for tight adhesion to this ligand. We, therefore, propose
      that podosomes provide an essential link between directional cell protrusion and
      achievement of DC translocation by establishing new dynamic anchor points at the
      front of the cell. The temporal regulation of podosome assembly during DC
      maturation also suggests that they may be most critical for early movement,
      perhaps during transmigration of lymphatic endothelium.

PMID- 14691952
TI  - The impacts of errors in individual genotyping and DNA pooling on association
      studies.
AB  - Case-control association studies using unrelated individuals may offer an
      effective approach for identifying genetic variants that have small to moderate
      disease risks. In general, two different strategies may be employed to establish
      associations between genotypes and phenotypes: (1) collecting individual
      genotypes or (2) quantifying allele frequencies in DNA pools. These two
      technologies have their respective advantages. Individual genotyping gathers more
      information, whereas DNA pooling may be more cost effective. Recent technological
      advances in DNA pooling have generated great interest in using DNA pooling in
      association studies. In this article, we investigate the impacts of errors in
      genotyping or measuring allele frequencies on the identification of genetic
      associations with these two strategies. We find that, with current technologies,
      compared to individual genotyping, a larger sample is generally required to
      achieve the same power using DNA pooling. We further consider the use of DNA
      pooling as a screening tool to identify candidate regions for follow-up studies.
      We find that the majority of the positive regions identified from DNA pooling
      results may represent false positives if measurement errors are not appropriately
      considered in the design of the study.

PMID- 14691953
TI  - Principal component analysis for selection of optimal SNP-sets that capture
      intragenic genetic variation.
AB  - Candidate gene association studies often utilize one single nucleotide
      polymorphism (SNP) for analysis, with an initial report typically not being
      replicated by subsequent studies. The failure to replicate may result from
      incomplete or poor identification of disease-related variants or haplotypes,
      possibly due to naive SNP selection. A method for identification of linkage
      disequilibrium (LD) groups and selection of SNPs that capture sufficient intra
      genic genetic diversity is described. We assume all SNPs with minor allele
      frequency above a pre-determined frequency have been identified. Principal
      component analysis (PCA) is applied to evaluate multivariate SNP correlations to
      infer groups of SNPs in LD (LD-groups) and to establish an optimal set of group
      tagging SNPs (gtSNPs) that provide the most comprehensive coverage of intra-genic
      diversity while minimizing the resources necessary to perform an informative
      association analysis. This PCA method differs from haplotype block (HB) and
      haplotype-tagging SNP (htSNP) methods, in that an LD-group of SNPs need not be a
      contiguous DNA fragment. Results of the PCA method compared well with existing
      htSNP methods while also providing advantages over those methods, including an
      indication of the optimal number of SNPs needed. Further, evaluation of the
      method over multiple replicates of simulated data indicated PCA to be a robust
      method for SNP selection. Our findings suggest that PCA may be a powerful tool
      for establishing an optimal SNP set that maximizes the amount of genetic
      variation captured for a candidate gene using a minimal number of SNPs.

PMID- 14691954
TI  - Power estimation of multiple SNP association test of case-control study and
      application.
AB  - At the current stage, a large number of single nucleotide polymorphisms (SNPs)
      have been deployed in searching for genes underlying complex diseases. A powerful
      method is desirable for efficient analysis of SNP data. Recently, a novel method
      for multiple SNP association test using a combination of allelic association (AA)
      and Hardy-Weinberg disequilibrium (HWD) has been proposed. However, the power of
      this test has not been systematically examined. In this study, we conducted a
      simulation study to further evaluate the statistical power of the new procedure,
      as well as of the influence of the HWD on its performance. The simulation
      examined the scenarios of multiple disease SNPs among a candidate pool, assuming
      different parameters including allele frequencies and risk ratios, dominant,
      additive, and recessive genetic models, and the existence of gene-gene
      interactions and linkage disequilibrium (LD). We also evaluated the performance
      of this test in capturing real disease associated SNPs, when a significant global
      P value is detected. Our results suggest that this new procedure is more powerful
      than conventional single-point analyses with correction of multiple testing.
      However, inclusion of HWD reduces the power under most circumstances. We applied
      the novel association test procedure to a case-control study of preterm delivery
      (PTD), examining the effects of 96 candidate gene SNPs concurrently, and detected
      a global P value of 0.0250 by using Cochran-Armitage chi(2)s as "starting"
      statistics in the procedure. In the following single point analysis, SNPs on
      IL1RN, IL1R2, ESR1, Factor 5, and OPRM1 genes were identified as possible risk
      factors in PTD.

PMID- 14691955
TI  - Analysis of SNPs in pooled DNA: a decision theoretic model.
AB  - Systematic analysis of the genetic background of complex diseases using single
      nucleotide polymorphisms (SNPs) affords a tremendous amount of genotypings. To
      reduce the amount of genotypings necessary and hence the overall cost of a case
      control study with SNPs, the genotyping is often performed in two stages. In the
      first, the DNA of all cases and all controls are mixed into two pools and
      genotyped for each SNP. The frequency of both alleles is determined in both
      pooled DNA samples. If different frequencies are observed in the pools of cases
      and controls, genotyping is performed individually in the second stage and
      analyzed conventionally. However, so far no well-founded algorithm is available
      to guide the decision on whether to genotype a SNP individually. In this report,
      an approach is introduced for the decision on individual genotyping based on the
      results from pooled DNA. The analysis is modeled as a decision process with the
      specific goal to decide on whether to genotype a specific SNP individually. For a
      given situation, the resulting decision criteria are aimed to be optimal for
      those conducting the study. Different loss functions and decision rules are
      presented. Using Monte-Carlo simulations, we show that for a given situation, the
      genotyping rates and hence the costs can be reduced remarkably while maintaining
      acceptable overall error rates.

PMID- 14691956
TI  - Tests for covariate-associated heterogeneity in IBD allele sharing of affected
      relatives.
AB  - Linkage studies that aim to map susceptibility genes for complex diseases
      commonly test for excess allele sharing among affected relatives. Conventional
      methods based on identical-by-descent IBD allele sharing do not allow for
      possible differences among families, such as arise in the case of locus
      heterogeneity, and thus have reduced ability to detect linkage in the presence of
      such heterogeneity. We investigated two approaches to test for heterogeneity in
      allele sharing, using a family-level covariate that may be associated with
      different disease mechanisms leading to differences in allele sharing. Likelihood
      ratio tests for heterogeneity were formulated based on an extension of the linear
      and exponential likelihood models developed by Kong and Cox. Alternatively, we
      examined the asymptotic and permutation distributions of T-tests for differences
      between mean allele-sharing linkage scores from two covariate-defined family
      subgroups, assuming exchangeability. The size and power of heterogeneity tests
      were evaluated for S(all) and S(pairs) allele-sharing scoring functions using
      data sets of families with affected sibling and cousin pairs, generated under a
      model of locus heterogeneity. In certain simulation scenarios, the likelihood
      ratio test statistics did not follow the expected asymptotic distributions. The
      type I error estimates for the T-statistics conformed to nominal 5 and 1% levels
      in all scenarios considered, and corresponding power was comparable to that of
      the likelihood ratio tests. Application of these tests for heterogeneity detected
      significant differences in allele sharing between subgroups of families with
      inflammatory bowel disease.

PMID- 14691957
TI  - Family-based tests for associating haplotypes with general phenotype data:
      application to asthma genetics.
AB  - We provide a general purpose family-based testing strategy for associating
      disease phenotypes with haplotypes when phase may be ambiguous and parental
      genotype data may be missing. These tests for linkage and association can be used
      in candidate gene studies with tightly linked markers. Our proposed weighted
      conditional approach extends the method described in Rabinowitz and Laird to
      multiple markers. It is attractive because it provides haplotype tests for family
      based studies that are efficient and robust to population admixture, phenotype
      distribution specification, and ascertainment based on phenotypes. It can handle
      missing parental genotypes and/or missing phase in both offspring and parents. It
      yields either haplotype-specific (univariate) tests or multi-haplotype (global)
      tests. This extension has been implemented in the freely available software
      haplotype FBAT. We used the haplotype FBAT program to test for associations
      between asthma phenotypes and single nucleotide polymorphisms (SNPs) in the beta
      2 adrenergic receptor gene. Whereas no single SNP showed significant association
      with asthma diagnosis or bronchodilator responsiveness (quantitative trait), a
      haplotype-based global test found a highly significant association with asthma
      diagnosis (P value <0.00005) and the measure of bronchodilator responsiveness (P
      value =0.016).

PMID- 14691958
TI  - Bayesian trio models for association in the presence of genotyping errors.
AB  - Errors in genotyping can greatly affect family-based association studies. If a
      mendelian inconsistency is detected, the family is usually removed from the
      analysis. This reduces power, and may introduce bias. In addition, a large
      proportion of genotyping errors remain undetected, and these also reduce power.
      We present a Bayesian framework for performing association studies with SNP data
      on samples of trios consisting of parents with an affected offspring, while
      allowing for the presence of both detectable and undetectable genotyping errors.
      This framework also allows for the inclusion of missing genotypes. Associations
      between the SNP and disease were modelled in terms of the genotypic relative
      risks. The performances of the analysis methods were investigated under a variety
      of models for disease association and genotype error, looking at both power to
      detect association and precision of genotypic relative risk estimates. As
      expected, power to detect association decreased as genotyping error probability
      increased. Importantly, however, analyses allowing for genotyping error had
      similar power to standard analyses when applied to data without genotyping error.
      Furthermore, allowing for genotyping error yielded relative risk estimates that
      were approximately unbiased, together with 95% credible intervals giving
      approximately correct coverage. The methods were also applied to a real dataset:
      a sample of schizophrenia cases and their parents genotyped at SNPs in the
      dysbindin gene. The analysis methods presented here require no prior information
      on the genotyping error probabilities, and may be fitted in WinBUGS.

PMID- 14691959
TI  - Pathways and destination of some male gland secretions in female Locusta
      migratoria migratorioides (R&F) after insemination.
AB  - The white secretions (WS) from the tubules of the male accessory glands (AG) of
      Locusta migratoria are composed of peptides and proteins. The WS are transferred
      during mating to the female's spermatheca. They have been followed to their
      destinations with immunological and radioactive marker techniques. In the
      spermatheca, peptides are split off from WS-protein complexes, permeate the
      spermathecal epithelium via glandular cells, enter the hemolymph and attach to
      other proteins in various target organs such as the dorsal fat body, the
      preterminal/terminal oocytes, and the follicular cells. In developing eggs, they
      concentrate at the posterior pole where sperm enters the egg, and in early
      embryogenesis they are found in the germ band. These results extend the functions
      of the spermatheca and the role of the male during the reproductive process.

PMID- 14691960
TI  - Stimulation of midgut stem cell proliferation by Manduca sexta alpha-arylphorin.
AB  - Extracts of the green-colored perivisceral fat body of newly ecdysed Manduca
      sexta pupae stimulate mitosis in midgut stem cells of Heliothis virescens
      cultured in vitro. Using a combination of cation- and anion-exchange
      chromatography, we have isolated a protein from these fat body extracts that
      accounts for the observed stem cell proliferation. SDS-PAGE analysis of the
      protein results in a single band of 77 kDa. Sequences of tryptic peptides from
      this protein are identical to internal sequences of the storage hexamer alpha
      arylphorin. The alpha-arylphorin isolated by our procedure represents a small
      fraction of the total arylphorin present in the fat body extract. However, it
      alone seems responsible for the stimulation of mitotic activity in H. virescens
      midgut stem cells.

PMID- 14691961
TI  - Relationship of adipokinetic hormone I and II to migratory propensity in the
      grasshopper, Melanoplus sanguinipes.
AB  - This report examines three aspects of adipokinetic hormone (AKH) involvement in
      migratory flight behavior in the grasshopper, Melanoplus sanguinipes. The titer
      of hemolymph AKH I during long-duration tethered flight was examined using
      radioimmunoassay (RIA) after narrow bore RP-HPLC. The hemolymph fraction
      containing AKH I was assayed using commercially available anti-Tyr1-AKH I serum.
      Titer determinations of hemolymph AKH were done at rest and after various periods
      of flight. The amount of AKH I released from the corpora cardiaca during flight
      was estimated. When resting levels of AKH I and II in corpora cardiaca (CC) of
      migrants and non-migrants were examined with HPLC, no significant differences in
      AKH levels were detected between non-migrants, animals that had flown for 1 h to
      identify them as migrants, and animals that had flown to exhaustion (i.e.,
      voluntary cessation). CC levels of both AKH I and II were less in this species
      than in locusts. When the lipid mobilization in response to AKH I and II was
      compared in migrants (animals that had self-identified as migrants in a 1-h
      tethered flight test) and non-migrants (animals that would not perform a 1-h
      flight in a tethered flight test), the adipokinetic response to AKH I was greater
      in migrants than in non-migrants, possibly indicating differences in level of
      sensitivity or number of receptors in the target tissues. AKH II had little
      effect on hemolymph lipid levels in either flight group, and may not play a
      significant role in lipid mobilization in this species.

PMID- 14691962
TI  - Immune stimulation in the silkworm, Bombyx mori L., by CpG oligodeoxynucleotides.
AB  - Synthetic ODNs containing unmethylated CpG dinucleotides are known to stimulate
      immune responses in vertebrates, but so far the effect has not been studied in
      insects. In this report, we describe an induction of immune response following
      injection of oligodeoxynucleotides (ODNs) into the insect hemocoel. The fifth
      instar silkworm (Bombyx mori L.) larvae were injected with several synthetic ODNs
      containing variable number of unmethylated CpG motifs, heat-denatured genomic DNA
      of B. mori itself, or intact genomic DNA to observe a new induction pattern in
      the insect immune mechanism. When the induction of immune response was examined
      based on the expression rates of genes for antibacterial peptides such as attacin
      and cecropin, we could confirm that it was triggered upon injection of ODNs. The
      expression was, however, neither dependent on numbers of CpG motifs nor
      methylation of CpGs in ODNs. Furthermore, it was confirmed that the presence of
      CpG in ODN was not involved in the induction pattern of insect immunity caused by
      ODNs, although it has been reported that vertebrates respond in a specific manner
      against invading ODNs containing CpG dinucleotides. In addition, insect immunity
      was not stimulated by injection of intact DNA from host. In contrast, the
      injection of denatured genomic DNA provoked the host immune reaction. Taken
      together, our data suggest that foreignness of ODNs or DNA might be a key factor
      in the induction of insect immunity.

PMID- 14691964
TI  - Occupational injury mortality surveillance in the United States: an examination
      of census counts from two different surveillance systems, 1992-1997.
AB  - BACKGROUND: The surveillance of occupational injury mortality in the United
      States has evolved over the last century. Currently there are two different data
      sources used for the study of occupational injury mortality. Each system varies
      in methodology, leading to different census counts. We provide an overview and
      analysis of similarities and differences in these two systems. METHODS: The
      National Traumatic Occupational Fatalities (NTOF) surveillance system and the
      Census of Fatal Occupational Injuries (CFOI) were examined for civilian deaths at
      work in the United States from 1992 to 1997. RESULTS: There were 31,643
      occupational injury mortality cases according to NTOF and 37,023 from CFOI for
      civilian workers 16-years and older in the United States for the 6-year period of
      analysis. The annual average occupational injury mortality rates were 4.5 per
      100,000 full time equivalent workers from NTOF and 5.2 from CFOI. The higher
      capture rate by CFOI was consistent across each of the 6 years. Similar patterns
      for demographics, industry, and occupation, and type of incident were seen for
      both systems. CONCLUSIONS: While NTOF provides more years of data dating back to
      1980, CFOI (established in 1992) provides a more comprehensive capture of
      occupational injury mortality and provides greater detail of the mortality
      incidents. The overall injury mortality patterns, however, appear to be similar
      between the systems.

PMID- 14691965
TI  - Acute occupational pesticide-related illness in the US, 1998-1999: surveillance
      findings from the SENSOR-pesticides program.
AB  - BACKGROUND: Concern about the adverse public health and environmental effects of
      pesticide use is persistent. Recognizing the importance of surveillance for acute
      occupational pesticide-related illness, we report on surveillance for this
      condition across multiple states. METHODS: Survey data collected between 1998 and
      1999 were obtained from the seven states that conduct acute occupational
      pesticide-related illness surveillance as part of the Sentinel Event Notification
      System for Occupational Risks (SENSOR) program. Data were collected by these
      state programs in a standardized manner and analyzed. Acute occupational
      pesticide-related illness incidence rates for those employed in agriculture and
      those employed in non-agricultural industries were also calculated. RESULTS:
      Between 1998 and 1999, a total of 1,009 individuals with acute occupational
      pesticide-related illness were identified by states participating in the SENSOR
      pesticides program. The mean age was 36 years, and incidence rates peaked among
      20-24 year-old workers. The overall incidence rate was 1.17 per 100,000 full time
      equivalents (FTEs). The incidence rate among those employed in agriculture was
      higher (18.2/100,000 FTEs) compared to those employed in non-agricultural
      industries (0.53/100,000 FTEs). Most of the illnesses were of low severity
      (69.7%). Severity was moderate in 29.6% of the cases, and high in four cases
      (0.4%). Three fatalities were identified. Insecticides were responsible for 49%
      of all illnesses. CONCLUSIONS: Surveillance is an important tool to assess acute
      pesticide-related illness, and to identify associated risk factors. Our findings
      suggest that these illnesses continue to be an important occupational health
      problem, especially in agriculture. As such, greater efforts are needed to
      prevent acute occupational pesticide-related illness.

PMID- 14691966
TI  - Cancer incidence rates among Lawrence Livermore National Laboratory (LLNL)
      employees: 1974-1997.
AB  - BACKGROUND: In the mid-1970's an excess of malignant melanoma of the skin was
      noted among employees at the Lawrence Livermore National Laboratory (LLNL). A
      1984 cancer incidence study showed a non-significant excess of total cancers
      among female employees with significant excesses for melanoma, rectum and anus,
      and salivary gland cancers. For male employees, there was a non-significant
      deficit of total cancer with significant excesses in melanoma and non-brain
      nervous system cancers. This paper reports the results of a surveillance effort
      to update our understanding of the patterns of cancer incidence in this
      population. METHODS: We used California Cancer Registry (CCR) data to ascertain
      employees who had worked for six or more consecutive months at LLNL during the 24
      year period of 1974 through 1997 who were diagnosed weith cancer during that time
      frame. We used the Standardized Incidence Ratio (SIR) in our analyses. RESULTS:
      There were 17,785 employees who provided 186,558 person-years of observation:
      145,203 were from males and 41,355 were from females. The CCR, through its
      linkage techniques, identified 541 individuals with invasive cancer and 96 with
      in situ cancer. A total of 404 males had invasive cancer and 33 had in situ
      cancer whereas there were 137 females with invasive cancer and 63 with in situ
      cancer. The SIR for invasive cancer in males was 69 (95% CI 62-76). The overall
      cancer SIR for males was unaffected by calendar time. There were only two
      invasive cancer sites with significant excess: melanoma and cancer of the testes.
      For eight categories or cancer sites, we found a statistical deficit in cancer
      incidence. The most striking deficit occurred in cancer of the lungs and bronchus
      with a SIR of 36 (95% CI 26-50). The SIR for invasive cancer in females was 80
      (95% CI 67-94). The overall cancer SIR for females decreased over calendar time.
      There was a statistically significant deficit for cancers of the female genital
      organs. There were 84 cases of invasive and in situ melanoma in both genders.
      Time-trend analyses for melanoma showed a significant excess during the years
      1974-1985 but a reduction to community rates from 1986 through 1997. There were
      21 individuals with testicular cancer with a SIR of 207 (95% CI 129-317). There
      were no differences in age at diagnosis or cell type with the comparison
      population. We analyzed the data using the same radiosensitive cancer categories
      used in the 1984 study. There were no increases in SIRs in any of these
      categories. CONCLUSIONS: We found that the LLNL employees had less cancer than
      expected with males having relatively fewer cancers than females. The lung cancer
      rate for males was remarkably low. Since 1986 the melanoma rates resemble the
      community rates. Testicular cancer rates are modestly elevated and appear to have
      been so for the past 20 years. Lifestyle patterns, including smoking, and cancer
      screening activities are probably important contributors to the observed low
      cancer rates.

PMID- 14691967
TI  - Cancer mortality among French Atomic Energy Commission workers.
AB  - BACKGROUND: All causes and cancer mortality of 58,320 workers employed at the
      Commissariat a l'Energie Atomique (CEA) between 1946 and 1994 were compared with
      that of the general population in a retrospective cohort study. METHODS:
      Standardized Mortality Ratios (SMR) were computed with reference to the French
      national population. RESULTS: Between 1968 and 1994, 4,809 deaths occurred. A
      healthy worker effect is observed for men (SMR = 0.57, CI(90%) = [0.56;0.59]) and
      for women (SMR = 0.72, CI(90%) = [0.67;0.77]). Nine sites of cancer death were
      found to be in statistically significant deficit among men, none among women. An
      excess of pleural cancers is observed among men (SMR = 1.79, CI(90%) =
      [1.27;2.45]) and of malignant melanoma (SMR = 1.50, CI(90%) = [1.04;2.11]). An
      excess of breast cancer is observed among women on the borderline of significance
      (SMR = 1.14, CI(90%) = [0.94;1.37]). CONCLUSIONS: Excesses observed will have to
      be related to occupational exposures in the on-going cohort study on French
      nuclear workers which includes a retrospective exposures assessment.

PMID- 14691968
TI  - Occupational fatalities of Hispanic construction workers from 1992 to 2000.
AB  - BACKGROUND: Hispanic construction employment has dramatically increased, yet
      published data on occupational risk is lacking. METHODS: Data from the Census of
      Fatal Occupational Injuries (CFOI) and current population survey (CPS) were
      examined from 1992 to 2000. Fatality rate, relative risk (RR), and risk index
      were calculated using CFOI fatality data and CPS data on hours worked, adjusted
      to full-time-equivalents (FTE). Data between 1996 and 2000 were combined to allow
      reliable comparisons of age and occupational groups. RR and 95% confidence
      intervals were calculated. RESULTS: In 2000, Hispanics constituted less than 16%
      of the construction workforce yet suffered 23.5% of fatal injuries. RRs were:
      helpers, construction trades, 2.31 (95% CI: 1.41-3.80); roofers 1.77 (95% CI:
      1.38-2.28); carpenters 1.39 (95% CI: 1.08-1.79); and construction laborers 1.31
      (95% CI: 1.17-1.46). CONCLUSIONS: Hispanic construction workers consistently
      faced higher RRs, for every year from 1992 to 2000 and for every age group. In
      2000, Hispanic construction workers were nearly twice (1.84, 95% CI: 1.60-2.10)
      as likely to be killed by occupational injuries as their non-Hispanic
      counterparts.

PMID- 14691969
TI  - Malignant mesothelioma in Italy, 1997.
AB  - BACKGROUND: The Italian National Mesothelioma Register (ReNaM) was set up at the
      Istituto Superiore Prevenzione e Sicurezza Lavoro (ISPESL), in Rome, in
      accordance with Art. 36 of Italian Legislative Decree No. 277 [1991]. METHODS:
      Five Italian regions, Piedmont, Liguria, Emilia-Romagna, Tuscany, and Apulia,
      agreed to record mesothelioma cases according to guidelines established by
      ISPESL, to define exposure to asbestos and transmit the data systematically to
      ISPESL. RESULTS: Four hundred and twenty-nine mesothelioma cases, diagnosed in
      1997, are recorded. The standardized annual incidence rate for definite pleural
      mesothelioma is 1.51 per 100,000 inhabitants (2.26 for males and 0.79 for
      females). Exposure was defined for 198 mesotheliomas with a histological
      diagnosis: 125 (63%) refer to occupational exposure, 10 (5%) to environmental
      exposure, and 5 (2.5%) to household exposure. CONCLUSIONS: Despite the ReNaM's
      work, many limitations still have to be overcome. Clear-cut information on
      asbestos exposure is available for a limited number of cases; and differing
      regional procedures in collecting and evaluating mesotheloma cases exist. At this
      stage the identification and evaluation of a large number of cases of
      mesothelioma is a worthwhile result. This epidemiological surveillance, currently
      being extended to other regions, will enable us to better assess the impact and
      diffusion of this disease in future, and to monitor more closely the effects of
      ceasing asbestos use in 1992, and the efficacy of preventive measures since mid
      '70s. Am. J. Ind. Med. 45:55-62, 2004.

PMID- 14691970
TI  - A survey on exposure level, health status, and biomarkers in workers exposed to 1
      bromopropane.
AB  - BACKGROUND: The aim of this study was to evaluate the health effects of exposure
      mainly to 1-bromopropane, which is an alternative to ozone-depleting solvents,
      and to establish biomarkers for assessing 1-bromopropane exposure. METHODS:
      Twenty-four female and 13 male workers of a 1-bromopropane-factory were
      interviewed, and their urine and blood samples were collected. Measured
      parameters included 1-bromopropane levels in the factory, as well as individual
      exposure levels, urinary 1-bromopropane levels, enzymatic activity and M
      subunit's concentration of serum creatine kinase (CK). RESULTS: Frequent symptoms
      reported by workers exposed to 1-bromopropane were nose, throat, and eyes
      irritation or malaise and/or headache. Urinary 1-bromopropane levels correlated
      significantly with individual exposure levels, but enzymatic activity or CK-M
      subunit did not. CONCLUSIONS: The symptoms suggested irritation of the mucous
      membrane and possible adverse effects on the central nervous system. There were
      no severe chronic symptoms suggestive of neurological damage in workers exposed
      to less than 170 ppm. Urinary 1-bromopropane level may be a good indicator of
      exposure. Am. J. Ind. Med. 45:63-75, 2004.

PMID- 14691971
TI  - Immunological and respiratory changes in tobacco workers.
AB  - BACKGROUND: Tobacco workers develop respiratory changes following occupational
      exposure to tobacco dust. METHODS: This study investigated 102 tobacco workers as
      well as a group of 30 matched control workers. Immunological testing, symptom
      questionnaire, and lung function measurements were performed in all workers.
      RESULTS: Increased total IgE was found in 12.7% of tobacco workers but in none of
      the controls (P < 0.05). Increased specific IgE (tobacco allergen) was recorded
      in 26.7% of tobacco workers with positive skin tests to tobacco extract but in
      none of the controls (P < 0.05). Regression analysis of ventilatory tests in
      female tobacco workers indicated a significant association of FEF75 to employment
      and smoking among workers with positive skin tests to tobacco. There were,
      however, no other associations between positive immunologic findings and lung
      function abnormalities and symptoms. CONCLUSIONS: Our study found increased
      immunological reactions in the tobacco workers. However, with the possible
      exception of lung function at low lung volume in female workers, these reactions
      do not appear to contribute significantly to the symptoms and lung function
      abnormalities seen in these workers. Am. J. Ind. Med. 45:76-83, 2004.

PMID- 14691972
TI  - Relationships between certain individual characteristics and occupational
      injuries for various jobs in the construction industry: a case-control study.
AB  - BACKGROUND: There is little published about the role of individual
      characteristics in occupational injuries. Construction workers have a high rate
      of injury; we assessed 11 personal characteristics in this professional sector.
      METHODS: A case-control study was conducted on 880 male workers who had had at
      least one occupational injury during a 2-year period and 880 controls. A
      questionnaire was administered by an occupational physician. Statistical analysis
      was made via logistic regression method. RESULTS: Young age (<30 years), sleep
      disorders and current smoker influenced all the injuries combined. Sleep
      disorders and young age were common risk factors for several jobs. Physical
      disabilities and no sporting activity had a role in masons, and 5 years or less
      in present job in plumbers and electricians only. Sleep disorders influenced both
      the injuries with and without hospitalization; young age, current smoker, and
      physical disability influenced those without hospitalization only. CONCLUSIONS:
      Young age, sleep disorders, smoking, disabilities, sporting activity, and
      experience influenced the occupational injuries. The risk for each worker
      depended on his job. Occupational physicians could inform the workers of these
      risks and encourage them to take remedial action.

PMID- 14691973
TI  - Mortality from cardiovascular disease in relation to magnetic field exposure:
      findings from a study of UK electricity generation and transmission workers, 1973
      1997.
AB  - BACKGROUND: Experimental and epidemiological studies have indicated that magnetic
      field exposure might influence heart rate variability and consequent risks of
      arrhythmia related deaths. METHODS: The mortality experience of a cohort of
      83,997 employees of the former Central Electricity Generating Board (CEGB) of
      England and Wales was investigated for the period 1973-1997. Cohort members were
      employed for at least 6 months from 1973 to 1982. Computerized work histories
      were available for 79,972 study subjects for the period 1971-1993. Detailed
      calculations had been performed by others to enable a novel assessment to be made
      of exposures to magnetic fields. Two analytical approaches were used, indirect
      standardization (n = 83,997) and Poisson regression (n = 79,972). RESULTS: Based
      on serial mortality rates for England and Wales, deaths from four categories of
      cardiovascular disease were below expectation: arrhythmia-related disease (ICD-9
      426-7), observed (obs) 32, expected (exp) 43.5, standardized mortality ratio
      (SMR) 74; acute myocardial infarction (ICD-9 410), obs 3,320, exp 3878.3, SMR 86;
      atherosclerosis (ICD-9 440), obs 25, exp 39.2, SMR 64; chronic/sub-acute coronary
      disease (ICD-9 411-414), obs 1,552, exp 2021.7, SMR 77). No statistically
      significant trends were shown for risks of any of these four disease groupings to
      increase either with lifetime cumulative exposure to magnetic fields or with such
      exposures received in the most recent 5 years. CONCLUSIONS: There are no
      discernible excess risks of mortality from cardiovascular diseases as a
      consequence of occupational exposure to magnetic fields in UK electricity
      generation and transmission workers.

PMID- 14691974
TI  - Integration of workers' compensation and health insurance prescription drug
      programs: how does it work and do employees use it?
AB  - BACKGROUND: In 1998, New York State designed and developed an integrated workers'
      compensation (WC)/health plan prescription drug program, ONECARD Rx, in response
      to cost inefficiencies within the then current system and in an attempt to
      improve the quality of care provided to WC claimants. This paper describes the
      benefit's design and development process and factors related to its use. METHODS:
      Users and non-users of the program were surveyed through a mailed questionnaire
      with appropriate telephone follow-up. RESULTS: Eight steps were followed in the
      development of the benefit. Results obtained from the assessment of ONECARD Rx
      suggest that factors affecting use mainly relate to the knowledge of both,
      employees and pharmacists, of the program. The two main differences detected
      between users and non-users included the state agency the employee works for and
      the site of residence. CONCLUSIONS: Innovative strategies that couple private and
      public agencies should aim at reducing the costs and eliminating inefficiencies
      while improving the quality of care, of which satisfaction is an important
      component.

PMID- 14691975
TI  - Exposure variability: concepts and applications in occupational epidemiology.
AB  - BACKGROUND: Standard approaches to assessing exposures for epidemiologic studies
      tend to concentrate resources on obtaining detailed data for each study
      participant at the expense of characterizing within-person variability. METHODS:
      This paper presents some basic, generalizeable concepts concerning exposure and
      its variability, describes methods that can be used to analyze, describe, and
      understand that variability, and reviews related implications for the design and
      interpretation of epidemiologic studies. RESULTS AND CONCLUSIONS: Insufficient
      attention to the balance of within- and between-person variation in exposure can
      reduce the efficiency of measurement efforts and attenuate estimates of exposure
      disease association. Exposure variability should consequently be considered
      carefully in the planning, analysis, and interpretation of epidemiologic studies.
      Greater attention to these matters can lead to more meaningful characterization
      of exposure itself, and, most importantly, improve the chances that epidemiologic
      studies can identify and accurately characterize health hazards.

PMID- 14691976
TI  - Evaluation of EMS-induced DNA damage in the single cell gel electrophoresis
      (Comet) assay and with flow cytometric analysis of micronuclei.
AB  - Toxic agents in the environment pose serious threats to ecosystems and to the
      public health. The single cell gel electrophoresis (SCGE) or Comet assay
      quantitatively measures genomic damage as DNA strand breaks. The micronucleus
      (MCN) test is an established assay that measures chromosomal damage. Micronuclei
      are formed from chromosome fragments or from whole chromosomes that have not
      undergone mitosis properly. This test is usually conducted microscopically.
      However, micronuclei can also be analyzed using flow cytometry. Chinese hamster
      ovary (CHO) cells were exposed to ethylmethanesulfonate (EMS), for 4 h in a total
      volume of 25 microl. These cells were immediately analyzed for genomic DNA damage
      by SCGE. In concurrent parallel experiments, CHO cells were treated with EMS in 6
      well plates for 4 h, the cells were washed and fresh medium was added. The cells
      were allowed to grow for 45 to 48 h to express micronuclei. The data demonstrated
      that both DNA strand breaks and micronuclei were induced in a significant and
      concentration-dependent manner. There was a significant and high correlation (r =
      0.91; P < or = 0.001) between the acute induction of DNA strand breaks and the
      subsequent generation of micronuclei. These data indicate that using molecular
      and computer technologies, the genotoxic impact of toxic and environmental agents
      can be rapidly and comprehensively evaluated in mammalian cell systems.

PMID- 14691977
TI  - Comet assay and flow cytometry analysis of DNA repair in normal and cancer cells
      treated with known mutagens with different mechanisms of action.
AB  - In order to determine differences in repair after treatment with DNA damaging
      agents, normal and cancer cells were selected for analysis of single strand
      breaks and DNA crosslinks using the Comet assay. Normal human lymphocytes, human
      colorectal adenocarcinoma SW620 cells, lung carcinoma A549, and H460 cell lines
      were exposed to an ethylating agent (ethylmethane sulfonate [EMS]), and a cross
      linking agent (mitomycin C [MMC]). Differences in repair profiles of DNA damage
      demonstrated using the comet assay were observed in human lymphocytes and tumour
      cell lines with both mutagens. Results were also indicative that MMC repair is
      concentration-dependent. It was also apparent that normal cells repair DNA damage
      more readily than tumour cells. Repair also varied between different cell lines.
      To investigate the mechanistic differences of these two chemicals, flow cytometry
      studies were undertaken in tumour cells, namely cell cycle analysis and frequency
      of micronuclei induction (FMN). A G2M phase block was clearly evident following
      treatment with EMS at all concentrations tested. With MMC, an initial arrest of
      cells in G2M was accompanied by a build-up in S-phase over longer exposure
      periods. Also, at the highest mutagen doses there were different patterns of
      micronuclei induction. Thus, using the mutagens with different mechanisms of
      action highlighted the differences in repair patterns between normal and tumour
      cells.

PMID- 14691978
TI  - Genotoxicity studies on DNA-interactive telomerase inhibitors with application as
      anti-cancer agents.
AB  - Telomerase-targeted strategies have aroused recent interest in anti-cancer
      chemotherapy, because DNA-binding drugs can interact with high-order tetraplex
      rather than double-stranded (duplex) DNA targets in tumour cells. However, the
      protracted cell-drug exposure times necessary for clinical application require
      that telomerase inhibitory efficacy must be accompanied by both low inherent
      cytotoxicity and the absence of mutagenicity/genotoxicity. For the first time,
      the genotoxicity of a number of structurally diverse DNA-interactive telomerase
      inhibitors is examined in the Ames test using six Salmonella typhimurium
      bacterial strains (TA1535, TA1537, TA1538, TA98, TA100, and TA102). DNA damage
      induced by each agent was also assessed using the Comet assay with human
      lymphocytes. The two assay procedures revealed markedly different genotoxicity
      profiles that are likely to reflect differences in metabolism and/or DNA repair
      between bacterial and mammalian cells. The mutational spectrum for a biologically
      active fluorenone derivative, shown to be mutagenic in the TA100 strain, was
      characterised using a novel and rapid assay method based upon PCR amplification
      of a fragment of the hisG46 allele, followed by RFLP analysis. Preliminary
      analysis indicates that the majority (84%) of mutations induced by this compound
      are C --> A transversions at position 2 of the missense proline codon of the
      hisG46 allele. However, despite its genotoxic bacterial profile, this fluorenone
      agent gave a negative response in the Comet assay, and demonstrates how unwanted
      systemic effects (e.g., cytotoxicity and genotoxicity) can be prevented or
      ameliorated through suitable molecular fine-tuning of a candidate drug in
      targeted human tumour cells.

PMID- 14691979
TI  - Oxygen-induced DNA damage in freshly isolated brain cells compared with cultured
      astrocytes in the Comet assay.
AB  - Brain cells are continuously exposed to reactive oxygen species generated by
      oxidative metabolism, and in certain pathological conditions defence mechanisms
      against oxygen radicals may be weakened and/or overwhelmed. DNA is a potential
      target for oxidative damage, and genomic damage can contribute to
      neuropathogenesis. It is important, therefore, to identify tools for the
      quantitative analysis of DNA damage in models of neurological disorders. The aim
      of this study was to compare the susceptibility of DNA to oxidative stress in
      cells freshly dissociated from the mouse brain, to that in cultured brain cells.
      Both primary cultures and a continuous cell line of astrocytes were considered.
      All cells were treated by xanthine/xanthine oxidase, a superoxide generator or
      hydrogen peroxide, applied alone or in the presence of the oxygen radical
      scavengers, superoxide dismutase, catalase, or ascorbic acid. DNA damage,
      quantified with the Comet assay, was consistent in all the different cell
      preparations exposed to oxidative stress, and was attenuated in similar ways by
      superoxide dismutase and catalase, scavengers of superoxide anion and hydrogen
      peroxide, respectively. The results with ascorbic acid were more variable,
      presumably because this compound may switch from anti- to pro-oxidant status
      depending on its concentration and other experimental conditions. Overall,
      similar responses were found in freshly dissociated and cultured brain cells.
      These results suggest that the Comet assay can be directly applied to cells
      freshly dissociated from the brain of rodents, including models of neurological
      disorders, such as stroke models and animals with targeted mutations that mimic
      human diseases.

PMID- 14691980
TI  - Antigenotoxic properties of selenium compounds on potassium dichromate and
      hydrogen peroxide.
AB  - Selenium is an environmental metal that occurs ubiquitously and is produced
      throughout the world for various industrial activities. Selenium has been
      reported to have anticarcinogenic and preventive effects in clinical and
      epidemiological studies. Selenium supplements can inhibit chemically-induced
      tumours. From the viewpoint of genotoxicity, selenium has not been adequately
      studied and an IARC review concluded that there were not sufficient data to
      consider it a carcinogen for man. In contrast, hexavalent chromium is classified
      as a known respiratory carcinogen producing DNA damage through free oxygen
      radicals. In the present study, a collaborative study has been carried out to
      evaluate the genotoxicity of selenium compounds and their possible interactions
      with potassium dichromate and hydrogen peroxide. Thus, in laboratory 1 (U.K.),
      the genotoxic effects of three selenium compounds were examined. Sodium selenate,
      sodium selenite, and selenous acid were investigated in the Ames test using
      strain TA102 and in the Comet assay using human lymphocytes, and also
      investigated for their interaction with potassium dichromate. In the Ames test,
      it was shown that potassium dichromate produced a highly mutagenic response,
      whilst the three selenium compounds did not. In combination, sodium selenate
      reduced the genotoxicity of potassium dichromate, but sodium selenite and
      selenous acid had no effect. In the Comet assay, potassium dichromate induced DNA
      damage, but so did the selenium compounds. In combination with potassium
      dichromate, however, only sodium selenate reduced its effect, whereas sodium
      selenite and selenous acid exacerbated DNA damage. In laboratory 2 (Spain), in
      the TK6 lymphoblastoid cell line, the Comet assay showed that sodium selenite was
      non-genotoxic, while potassium dichromate and hydrogen peroxide induced DNA
      damage. It was also shown that sodium selenite did not decrease the genotoxicity
      of potassium dichromate or hydrogen peroxide when administered as a pre-treatment
      or at the same time, or when potassium dichromate and sodium selenite treatments
      were for different time periods. Thus, only sodium selenate has shown
      antigenotoxic properties against potassium dichromate in the Ames test and in
      human lymphocytes in the Comet assay.

PMID- 14691981
TI  - The effect of the antioxidant catalase on oestrogens, triiodothyronine, and
      noradrenaline in the Comet assay.
AB  - Metabolic changes in the phenolic groups of steroidal oestrogens accompanied by
      the generation of quinones and reactive oxygen species underlie their mutagenic
      effects. Although nonsteroidal hormones and related compounds have not been
      thoroughly investigated for genotoxicity, some of them also contain phenolic
      groups that could be involved in redox cycling. Therefore, the aim of the present
      study was to evaluate the possible DNA damaging effects of the thyroid hormone,
      triiodothyronine (T3), and the neurotransmitter, noradrenaline (NA), in human
      lymphocytes using the Comet assay. After dose-response investigations, doses of
      100 microM T3 and 550 microM of NA, producing clear DNA damaging effects and good
      cell viability, were chosen for further experiments with the antioxidant,
      catalase. Since the scavenging enzyme catalase reduced the DNA damaging effects
      of T3 and NA, it can be concluded that T3 and NA induced DNA damage mainly via
      the production of reactive oxygen species. Therefore, the mechanism of mutagenic
      action of both steroidal hormones and nonsteroidal compounds, T3 and NA, imply
      the creation of oxidative stress and subsequent DNA damage with reactive oxygen
      species and, possibly, with reactive hormone derivatives created during their
      redox cycling.

PMID- 14691982
TI  - Sensitivity of different thalassaemia genotypes to food mutagens in the Comet
      assay.
AB  - Thalassaemia is a heterogeneous group of inherited anaemias, characterised by a
      reduction or total absence of one or more of the globin chains of haemoglobin.
      Individuals with thalassaemia major require regular blood transfusions in order
      to maintain their haemoglobin concentration at an appropriate level. An essential
      treatment in parallel with transfusions is iron chelation therapy to remove
      excess iron deposited in tissues from the transfused blood. The high iron levels
      in these patients make free oxygen radicals accessible, for example, through
      Fenton-type chemistry, and generate superoxide and hydroxyl radicals. Increased
      oxygen radical capacity is known to be associated with cancer and ageing. In a
      previous study, it has been shown that peripheral blood lymphocytes isolated from
      a sickle/beta thal double heterozygote-sickle phenotype thalassaemia patient, who
      was not undergoing chelation therapy, showed increased sensitivity to the effects
      of oxygen radicals and iron salts by comparison with lymphocytes from normal
      controls. Furthermore, in a later study, this patient also showed increased
      sensitivity to the dietary food mutagen 3-amino-1-methyl-5H-pyridol(4,3-b)indole
      (Trp-P-2) when compared to the control. The present study, therefore,
      investigated whether the above observation could be duplicated using different
      food mutagens in different thalassaemia genotypes. The effect of the food
      mutagens 2-amino-2-methylimidazolo(4,5-f)quinolone (IQ) and 2-amino-1-methyl-6
      phenylimidazol(4,5-b)pyridine (PhIP) on lymphocytes of three different
      thalassaemia patients, a beta-thalassaemia major, a beta-thalassaemia/Hb E, and
      an alpha-thalassaemia trait with a 3.7-kb deletion, who were not undergoing
      chelation therapy were investigated using the Comet assay. All three thalassaemia
      genotypes showed increased sensitivity to both IQ and PhIP in comparison to the
      control, although with PhIP at the highest two concentrations (50 and 75 microM)
      the differences monitored with the alpha-thalassaemia trait were found not to be
      statistically significant (P > 0.05).

PMID- 14691983
TI  - Modulation by flavonoids of the effects of a food mutagen in different
      thalassaemia genotypes in the Comet assay.
AB  - Thalassaemia is an inherited group of disorders caused by a reduction or total
      absence of one or more of the globin chains of the haemoglobin molecule. It has
      been shown that lymphocytes isolated from a sickle/beta thal double heterozygote
      sickle phenotype patient showed increased sensitivity to the dietary food mutagen
      3-amino-1-methyl-5H-pyridol(4,3-b)indole (Trp-P-2) when compared to the control.
      Furthermore, when a combination of Trp-P-2 with either quercitin or kaempferol
      was compared, the responses to Trp-P-2 were reduced to untreated control levels
      at the highest doses of quercitin and kaempferol. It has now been shown that
      using the food mutagens 2-amino-2-methylimidazolo(4,5-f)quinolone (IQ) and 2
      amino-1-methyl-6-phenylimidazol(4,5-b)pyridine (PhIP) on lymphocytes of three
      different thalassaemia patients, a beta-thalassaemia major, a beta
      thalassaemia/Hb E, and an alpha-thalassaemia trait with a 3.7-kb deletion,
      similar increased sensitivity could also be demonstrated. The present study
      investigated whether the modulatory effects of the flavonoids could be
      demonstrated in lymphocytes isolated from a beta-thalassaemia major and a beta
      thalassaemia/Hb E patient. Lymphocytes from both a beta-thalassaemia major and
      beta-thalassaemia/Hb E patient showed increased sensitivity to PhIP when compared
      to the normal control. When a combination of PhIP and either quercitin or
      kaempferol was used, a reduction in the responses was seen, and at the highest
      doses of quercitin and kaempferol the responses were reduced to near untreated
      control levels and were significantly different when compared to PhIP alone (P <
      0.05). It was concluded that lymphocytes from different thalassaemia genotypes
      showed increased sensitivity to different dietary food mutagens compared to
      normal lymphocytes and that flavonoids such as quercitin and kaempferol modulated
      the effects of these food mutagens in an antigenotoxic/antioxidant manner.

PMID- 14691984
TI  - Effect of age on testicular germ cell apoptosis and sperm aneuploidy in MF-1
      mice.
AB  - The spontaneous mutation rate in the male germ-line increases with age. The
      reason for this is unknown, but presumably involves an age-related degeneration
      in the efficacy of cellular processes. To investigate the possibility that rates
      of apoptosis and genetic damage (represented by aneuploidy) might vary with age
      in mice, the testes and sperm of 2- and 12-month-old male MF-1 mice were examined
      by a modified TUNEL technique and 3-colour sperm-FISH assay, respectively. Sperm
      were labeled with probes to chromosomes 8, X and Y and 20,000 sperm scored from
      each of 5 animals per group. A significant increase in gonosomal disomy was found
      in the aged mice, especially X-X-8. This suggests that advanced paternal age is
      associated primarily with meiosis II rather than meiosis I disjunction errors.
      Neither diploidy nor autosomal disomy was affected in the older group. The rate
      of germ cell apoptosis (apoptotic cells per seminiferous tubule cross-section per
      animal per group) was higher in the old mice than controls, but not
      significantly. Considerable inter-animal variability was observed in the older
      group. The finding of an increase in levels of sperm aneuploidy is novel for 1
      year-old mice and confirms the genotoxic effect of ageing in mice. Since
      apoptosis is assumed to eliminate cells with unrepaired damage, it may be that
      the apoptotic response in older mice is compromised, resulting in the higher
      levels of aneuploidy in sperm. However, given the inter-animal variability in
      testicular germ cell apoptosis, this awaits confirmation.

PMID- 14691987
TI  - Fetal cystoscopy in the management of fetal obstructive uropathy: experience in a
      single European centre.
AB  - OBJECTIVE: To audit diagnostic and therapeutic fetal cystoscopy for suspected
      posterior urethral valves (PUV). METHODS: In 13 fetuses, (14-28 weeks) the
      bladder was entered with a 1.3 mm embryo-fetoscope and intravesical findings
      documented. In 10 fetuses, an attempt was made to treat the obstruction by saline
      hydro-ablation (n = 4) and/or guide-wire passage (n = 9). Renal function was
      assessed post-natally at 10 to 34 months. RESULTS: The bladder wall was
      visualised in 12/13 cases and the bladder neck in 11; in 10 cases the upper
      urethra was entered, and the obstruction visualised in five. PUV were 'seen' in
      4/9 confirmed cases, but also in one case of urethral atresia, while in two
      others the degree of resistance to guide-wire passage suggested atresia or prune
      belly. Therapeutic attempts were technically successful, at least initially, in
      6/10 cases. Of the five cases with confirmed PUV and normal fetal urinary
      electrolytes, two have acceptable renal function at follow-up. Hydro-ablation in
      one case resulted in resolution of sonographic signs of obstruction, and ablated
      valves were confirmed post-natally. CONCLUSIONS: Semi-rigid fetal cystoscopy
      allows entry into the upper urethra in most obstructive uropathies, although
      bladder neck angulation precludes visualisation of the site of obstruction in the
      majority. Guide-wire passage or hydro-ablation may allow relatively atraumatic
      ablation of PUV in utero without the chronic bladder decompression associated
      with vesico-amniotic shunting. However, current technical limitations need to be
      overcome, possibly by the use of flexible or angled fetoscopes, before the role
      of cystoscopic treatment can be formally evaluated.

PMID- 14691988
TI  - Earliest gestational age for fetal sexing in cell-free maternal plasma.
AB  - OBJECTIVES: To evaluate at what gestational age fetal DNA can reliably be
      detected at the earliest in maternal plasma. METHODS: We performed consecutive
      blood sampling in the first trimester of pregnancy in 17 women who were pregnant
      after in vitro fertilization (IVF) or intrauterine insemination (IUI). DNA was
      isolated and the Y-chromosome specific SRY was amplified by real-time polymerase
      chain reaction (PCR). We likewise studied 31 women prior to invasive prenatal
      diagnosis procedures for test validation purposes. All test results were compared
      to cytogenetic sex or sex at birth. RESULTS: The earliest SRY detection was at a
      gestational age of 5 weeks and 2 days. In none of 4 pregnancies ending in a
      miscarriage was SRY detected. We detected SRY in maternal plasma in 1 of 2
      patients (50%) carrying a male fetus at a gestational age of 5 weeks, in 4 of 5
      (80%) at a gestational age of 7 weeks, in 4 of 4 (100%) at a gestational age of 9
      weeks. In all 7 women pregnant with a male fetus, the correct fetal sex was
      detected by 10 weeks. In none of the 6 patients who delivered a girl was SRY
      detected. In the validation group, SRY was detected in 13 of the 13 male, and
      none of the 18 female fetuses. CONCLUSIONS: We conclude that real-time PCR of the
      SRY gene promises to be a reliable technique for early fetal sexing in maternal
      plasma.

PMID- 14691989
TI  - Maternal midtrimester free beta-HCG and AFP serum levels in spontaneous singleton
      pregnancies complicated by gestational diabetes mellitus, pregnancy-induced
      hypertension or obstetric cholestasis.
AB  - OBJECTIVES: The present study aims at finding out whether a connection exists
      between altered serum free beta-hCG and/or alpha-fetoprotein (AFP) levels and the
      manifestation of specific pregnancy complications [i.e. gestational diabetes
      mellitus (GDM), pregnancy induced hypertension (PIH) or intrahepatic cholestasis
      of pregnancy (ICP)]. METHODS: We compared free beta-hCG and AFP multiples of
      median (MoM) values in singleton pregnancies. The study population consisted of
      117 pregnancies with GDM, 107 with PIH and 24 with ICP. The control group
      consisted of 1148 singleton pregnancies without any pregnancy complications. All
      were spontaneously conceived. RESULTS: In the group with GDM, both the free beta
      hCG (0.72 MoM) and AFP MoM values (0.93) were significantly lower than in
      controls (beta-hCG 0.97 MoM, p = 0.0063 and AFP 1.01 MoM, p = 0.01). No
      statistically significant differences in the marker levels were observed between
      the ICP pregnancies and the control group. CONCLUSIONS: GDM has an impact on
      maternal midtrimester free beta-hCG and AFP levels and may change the DS
      screening result.

PMID- 14691990
TI  - The influence of needle and syringe size on chorionic villus sampling of term
      placentae: a randomised trial.
AB  - OBJECTIVE: To determine the effect of needle and syringe size on the amount of
      tissue obtained at chorionic villus sampling METHODS: Two needle sizes, 18 and 20
      gauge, and two syringe sizes 5 mL and 20 mL, were used to assess samples from
      term post-partum placentae. Each of the four combinations was tested by 25
      aspirations. The placentae were divided into 100 grid spaces and each grid space
      was randomly allocated to a needle/syringe combination. The resulting samples
      were cleaned to separate the chorionic villi (CV), centrifuged and then weighed.
      RESULTS: Significantly more tissue was obtained with an 18-g needle compared with
      a smaller 20-g needle (median weight difference 1.5 mg, 95% CI 0.8-2.3 mg). More
      tissue was also obtained with the larger 20-mL syringe though the impact of the
      syringe size was less than that of the needle size (median difference 0.8 mg, 95%
      CI 0-1.6). CONCLUSION: A larger syringe and needle size yields a larger quantity
      of chorionic villi from the post-partum term placenta.

PMID- 14691991
TI  - The 'in-plane' view of the inter-ventricular septum. A new approach to the
      characterization of ventricular septal defects in the fetus.
AB  - OBJECTIVES: Objectives of this study are (1) to describe how to obtain the in
      plane view of the inter-ventricular septum, (2) to assess its feasibility in a
      population of fetuses referred for fetal echocardiography, (3) to demonstrate its
      effectiveness in the characterization of VSD in the fetus. METHODS: The in-plane
      view of the inter-ventricular septum is conducted in a plane almost perpendicular
      to that of the long axis of the left ventricle, tilting the transducer towards
      the right ventricle, paying attention not to 'enter' the right ventricular
      chamber. Its feasibility has been assessed in 41 fetuses referred for fetal
      echocardiography, by recording the visualization/failure rates by fetal lie and
      acoustic window. The in-plane view of the inter-ventricular septum was then
      employed in healthy fetuses and diseased fetuses with VSDs. RESULTS: The success
      rates in obtaining the in-plane view of the inter-ventricular septum was
      dependent upon fetal lie; visualization rates were 100, 36 and 0% in case of
      posterior, lateral and anterior spine, respectively. When used in the anatomic
      characterization of VSDs, this view provided significant additional information.
      CONCLUSIONS: The in-plane view of the inter-ventricular septum represents a new
      echocardiographic view that can be used to enhance the assessment of the inter
      ventricular septum of the fetal heart. Its use should be considered whenever the
      presence of a VSD is suspected during fetal echocardiography, and in these cases
      it often provides additional information.

PMID- 14691992
TI  - Ossification timing of sacral vertebrae by ultrasound in the mid-second trimester
      of pregnancy.
AB  - OBJECTIVES: The aim of the study was to establish the ossification timing of
      sacral vertebrae by ultrasonography in the second trimester of pregnancy, for the
      diagnosis of caudal regression syndrome with isolated sacral agenesis. METHODS:
      The study was carried out on 77 normal single pregnancies, at gestational ages
      ranging from 15 to 21 weeks, using high-resolution transabdominal echography. The
      sacral region was visualized in a coronal plane, when the fetus was in
      anterodorsal position. The level of ossification of sacral vertebrae (S1 to S5)
      at each gestational age was recorded. Each sacral region was examined three times
      by the same observer and the nucleus was considered as present when it was
      visualized at least two times out of three. Blind assessment was performed three
      times by a second observer, who was not present at the previous examination, for
      interobserver and intraobserver error analysis. RESULTS: Interobserver and
      intraobserver error calculation demonstrated the reproducibility of the method.
      Concordance between the two observers as evaluated by Cohen Kappa index was 0.77
      (C.I. 95%, 0.69-0.85).S1 ossification nuclei were visualized in all fetuses at 15
      weeks and S2 nucleus was found in all fetuses within 17 weeks. S3 nucleus was
      detected in 45% of fetuses by the beginning of the 16th week. S4 was visualized
      in 55% of the cases at 18 weeks and progressively in a higher percentage of cases
      during the following weeks of gestation. CONCLUSION: The data obtained showed
      that the sequence of development of sacral region ossification was related to
      gestational age. This observation allows clinicians to accurately exclude
      isolated sacral agenesis at 16 to 17 weeks of gestation, when the S1-S2
      ossification nuclei are visualized. This opportunity may be of particular value
      in the offspring of diabetic mothers.

PMID- 14691993
TI  - Providing letters and audiotapes to supplement a prenatal diagnostic
      consultation: effects on later distress and recall.
AB  - OBJECTIVES: Information provided at a mid-trimester fetal scan aims to improve
      patients' knowledge and minimize anxiety. This randomized controlled trial
      conducted at the Fetal Medicine Centre at Birmingham Women's Hospital aimed to
      assess the relative value of providing 1.standard information: a consultation and
      computer-generated ultrasound report (n = 29); 2.standard information plus a post
      scan written non-technical letter (n = 29); 3.standard information plus
      audiotapes of the consultation (n = 29); 4.standard information plus both non
      technical letters and audiotapes (n = 30). It also aimed at exploring whether
      severity of diagnosis (none; mild; moderate-severe) interacted with the type of
      information provided to affect subsequent anxiety, depression and recall of
      information. PARTICIPANTS: Women (n = 550) referred with suspected fetal
      anomalies (without a previous history of anomaly or known psychiatric illness)
      were sent information regarding this study. One hundred and seventeen women
      consented and were randomly assigned to one of four information groups. The
      groups were similar with regard to age, education and marital status. MAIN
      OUTCOME MEASURES: State anxiety and depression were evaluated with the self
      report State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI)
      prior to consultation and two weeks post-scan. A structured telephone interview
      assessed recall of information approximately two weeks later. RESULTS: Two weeks
      after the initial consultation, women who received an audiotaped recording of the
      consultation reported significantly less anxiety than the control group (mean
      STAI 41.44 [95% CI 35.63-47.26] versus 44.92 [39.32-50.52]; difference = 10.70
      [3.56-17.83], p < 0.01). Women who received a non-technical letter also reported
      less anxiety than the control group, an effect that approached significance (mean
      STAI 39.08 [95% CI 32.85-45.30]; difference = 6.48 [0.21-13.16], p = 0.058).
      There were no differences between the information groups on depression scores or
      recall of information. Women with a more severe abnormality reported higher
      anxiety and depression two weeks post-consultation, and had greater free recall
      but less cued recall of information. CONCLUSIONS: Provision of additional
      material (particularly an audiotape) following a prenatal scan appears to
      minimise anxiety compared with standard practice. Provision of audiotapes and non
      technical letters do not appear to affect patient recall.

PMID- 14691994
TI  - Fetal karyotyping after 28 weeks of gestation for late ultrasound findings in a
      low risk population.
AB  - OBJECTIVE: To analyze the indications and the results of invasive testing for
      fetal karyotyping for ultrasound abnormality in the third trimester of pregnancy,
      when first- and second-trimester screening tests were negative. METHODS:
      Retrospective study of 171 consecutive pregnancies that underwent invasive
      testing after 28 weeks of gestation in 2 institutions between January 1999 and
      December 2001. Forty-one patients did not have any form of screening for fetal
      aneuploidy beforehand. One hundred and thirty of them had a normal first
      trimester scan and a low risk of fetal aneuploidy by nuchal translucency and/or
      maternal serum screening and were included in the statistical analysis. RESULTS:
      Mean maternal age, gestational age at diagnosis and at invasive testing were 30.5
      years; 29.3 weeks and 32.5 weeks respectively. Amniocentesis and fetal blood
      sampling were performed in 97 and 33 cases respectively. The most frequent
      indications for invasive testing in the third trimester were major fetal
      malformations (51%) and intrauterine growth restriction (19%) detected on routine
      second- or third-trimester ultrasound examination. Ultrasound markers of
      aneuploidy and polyhydramnios accounted for 17 and 11% of the indications
      respectively. Fetal karyotype was normal in 121/130 cases. A gene mutation was
      found in one case. The karyotype was abnormal in nine cases, including seven
      cases of aneuploidy (one Turner syndrome, three trisomy 18, and three trisomy 21)
      and two cases of structural chromosomal abnormalities (46,XX, del 4 p16.1 and
      46,XX, dup1). One hundred cases resulted in the delivery of a normal baby. Thirty
      cases led to termination of pregnancy or intrauterine death due to major fetal
      malformations (N = 25), abnormal karyotype in six of these, and severe IUGR (N =
      5) with normal karyotype. Fetal US markers of aneuploidy and isolated
      polyhydramnios were associated with a favorable outcome in all cases.A
      significant increase in the risk of chromosomal anomaly was seen when two or more
      anomalies were found, rising from 2% with one anomaly to 21% when two or more
      anomalies were present. CONCLUSION: In low risk patients, fetal karyotyping in
      the third trimester may be justified when the diagnosis of fetal malformation is
      made in the third trimester of pregnancy. Two or more anomalies increase the risk
      of fetal aneuploidy even with a negative-screening test in the first and second
      trimester of pregnancy.

PMID- 14691995
TI  - Medically assisted reproduction and second-trimester maternal serum marker
      screening for Down syndrome.
AB  - OBJECTIVES: To evaluate the effect of in vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI) on total hCG, free ss-hCG, AFP and
      unconjugated estriol (uE3) used as markers for second-trimester Down syndrome
      maternal serum screening. METHODS: Second-trimester maternal sera from 1515
      singleton pregnancies (970 by IVF, 545 by ICSI) were compared with control sera
      (21 014 cases). Free ss-hCG, total hCG, AFP and uE3 were compared between the
      control group and the medically assisted reproduction groups. The percentages of
      at-risk patients (>/=1/250) were also compared. RESULTS: No differences in values
      of the maternal serum markers were observed between the medically assisted and
      control groups. When maternal age was taken into account, the screen-positive
      rate for Down syndrome screening did not differ between the two groups.
      CONCLUSION: Patients undergoing assisted reproduction techniques can be counseled
      for maternal serum Down syndrome screening with the same efficacy as patients
      with naturally conceived pregnancies.

PMID- 14691996
TI  - Free fetal DNA concentration in maternal plasma during normal labour at term.
AB  - OBJECTIVE: Our aim was to investigate the effect of uterine contractions on free
      fetal DNA concentration in maternal plasma at term. STUDY DESIGN: Nine pregnant
      women were admitted for elective induction of labour between 38 and 40 weeks of
      gestation. All patients carrying male fetuses and without history of pre-term
      labour and membrane rupture were selected. Maternal venous blood samples were
      serially collected every hour during labour, one hour after delivery and 24 h
      after delivery. In order to amplify fetal and total free DNA, primers for SRY and
      GAPDH genes were respectively chosen. Real- time PCR analysis was performed with
      an GeneAmp 5700 Sequence Detection System (Applied Biosystems Foster City, USA).
      Statistical significance was determined using the Wilcoxon test. RESULT: Median
      concentration of fetal DNA in plasma before labour was 3081 copies/mL (Range 812
      15 864 copies/mL). No significant difference between the number of copies per
      millilitre before any contractions and during labour was demonstrated. One hour
      after delivery, significant decrease in the fetal DNA rate was observed with a
      median concentration of 293 copies/mL (Range 0-2037 copies/mL) (p-value: 0.04).
      This drop was more significant 24 h after delivery with a median concentration of
      0 copies/mL (Range 0-95 copies/mL) (p-value: 0.02). CONCLUSIONS: During labour,
      no changes in free fetal DNA in maternal plasma were demonstrated. This suggests
      that labour does not have effect on free fetal DNA release in maternal
      circulation at term.

PMID- 14691997
TI  - First report of prenatal diagnosis of genetic congenital deafness in a routine
      prenatal genetic test.
AB  - OBJECTIVE: We aimed to screen for connexin26 gene (GJB2) mutations associated
      with autosomal recessive non-syndromic neurosensory deafness (NSRD) in a general
      risk population. METHODS: Screening for the most common connexin26 gene mutations
      was offered to all women undergoing a second-trimester amniocentesis for fetal
      karyotype analysis in our Center. After rapid DNA extraction from amniotic fluid,
      PCR amplification was performed and products analysed to detect mutations of GJB2
      gene by a sequencing technique. In particular, we searched for the 20 most
      frequently reported mutations (out of the approximately 90 so far described) and
      for which there are commercially available tests. RESULTS: From a total of 4819
      consecutive amniotic fluids examined, the following five different heterozygous
      mutations were detected: 35delG in 80 cases, 167delT in 3 cases and 1 occurrence
      of each of the following mutations: M34T, 35insG and W77R. From these data, a
      prevalence of 1 : 56 (1.78%) for the heterozygous condition can be estimated in
      the Mediterranean general risk population. The striking predominance of 35delG
      mutation is confirmed. In addition, we detected a homozygous 35delG mutation
      condition in a foetus of no risk parents. In this case, the early diagnosis
      permitted prompt application of an acoustic prosthesis allowing for cochlear
      implantation in due time, with significant improvement of the prognosis.
      CONCLUSIONS: In a general risk population, a carrier status for congenital
      deafness can be observed in 1 : 56 (1.78%) amniotic fluids; this is mostly due to
      the presence of a 35delG mutation of the connexin26 gene. Occasional
      identification of homozygous states, although rare, allows the best therapeutic
      approach.

PMID- 14691998
TI  - ADAM12: a novel first-trimester maternal serum marker for Down syndrome.
AB  - OBJECTIVES: The concentration of bioavailable insulin-like growth factor (IGF) I
      and II is important to foetal growth. It is regulated by insulin-like growth
      factor binding proteins (IGFBP) 1 through 6. Proteolytic cleavage of IGFBP-3
      takes place in human pregnancy serum; accordingly, IGFBP-3 serum levels decrease
      markedly during pregnancy. ADAM12 (A disintegrin and metalloprotease) is an IGFBP
      3 and IGFBP-5 protease and is present in human pregnancy serum. The goal of this
      study was to determine whether ADAM12 concentration in maternal serum is a useful
      indicator of foetal health. METHODS: We developed an enzyme-linked immunosorbent
      assay (ELISA) for the quantification of ADAM12 in serum. The assay range was 42
      to 667 micro g/L. Recombinant ADAM12 was used as the standard for calibration.
      RESULTS: We found that ADAM12 was highly stable in serum. Serum concentration
      increased from 180 micro g/L at week 8 of pregnancy to 670 micro g/L at 16 weeks,
      and reached 12 000 micro g/L at term. In 18 first-trimester Down syndrome
      pregnancies, the concentration of ADAM12 was decreased, thus the median multiple
      of mean (MoM) value was 0.14 (0.01-0.76). A detection rate for foetal Down
      syndrome of 82% for a screen-positive rate of 3.2% and a 1:400 risk cut-off was
      found by Monte Carlo estimation using ADAM12 and maternal age as screening
      markers. CONCLUSION: ADAM12 is a promising marker for Down syndrome.

PMID- 14691999
TI  - Rapid prenatal diagnosis of X-linked chronic granulomatous disease using a
      denaturing high-performance liquid chromatography (DHPLC) system.
AB  - OBJECTIVE: To describe a family on whom it was possible to perform a rapid
      prenatal diagnosis for chronic granulomatous disease (CGD) using a denaturing
      high-performance liquid chromatography (DHPLC) system. METHODS: For a family
      whose first-born, a boy, suffered from X-linked chronic granulomatous disease,
      fetal DNA was obtained from an ongoing pregnancy by amniocentesis early in the
      second trimester. Denaturing high-performance liquid chromatography and direct
      sequencing were used to attempt to detect the previously identified X-linked
      chronic granulomatous disease mutation. RESULTS: Our studies predicted that the
      fetus in question was not likely to be affected by chronic granulomatous disease,
      which was demonstrated to be correct at birth. CONCLUSIONS: Here, we introduce a
      molecular diagnostic tool (DHPLC) for an effective and exact prenatal diagnosis
      of normality for the second-born child, as determined from amniocentesis during
      the second trimester.

PMID- 14692000
TI  - Are some cases of sudden intrauterine unexplained death due to the long QT
      syndrome?

PMID- 14692001
TI  - Congenital toxoplasmosis: necessity of clinical and ultrasound follow-up despite
      negative amniocentesis.

PMID- 14692002
TI  - Prenatal imaging of the fetal anterior chest wall cystic hygroma by magnetic
      resonance imaging.

PMID- 14692003
TI  - Uptake of prenatal screening for chromosomal anomalies: impact of test results in
      a previous pregnancy.

PMID- 14692004
TI  - Trisomy 13 manifested as hypoplastic left heart and other structural
      abnormalities.

PMID- 14692005
TI  - Recommendations for applying tests of equivalence.
AB  - Researchers in psychology reliably select traditional null hypothesis
      significance tests (e.g., Student's t test), regardless of whether the research
      hypothesis relates to whether the group means are equivalent or whether the group
      means are different. Tests of equivalence, which have been popular in
      biopharmaceutical studies for years, have recently been introduced and
      recommended to researchers in psychology for demonstrating the equivalence of two
      group means. However, very few recommendations exist for applying tests of
      equivalence. A Monte Carlo study was used to compare the test of equivalence
      proposed by Schuirmann with the traditional Student t test for deciding if two
      group means are equivalent. It was found that Schuirmann's test of equivalence is
      more effective than Student's t test at detecting population mean equivalence
      with large sample sizes; however, Schuirmann's test of equivalence performs
      poorly relative to Student's t test with small sample sizes and/or inflated
      variances.

PMID- 14692006
TI  - Psychometric properties of the Brief Life Satisfaction Scales.
AB  - The development, psychometric characteristics, and clinical utility of a brief
      measure of life satisfaction, the Brief Life Satisfaction Scales (BLSS), are
      presented. Factor analysis of the 10-item scale yielded three factors: self
      satisfaction, interpersonal satisfaction, and social role satisfaction.
      Reliability (internal consistency and retest) and validity (concurrent,
      construct, discriminant, known group, predictive, and incremental) were adequate
      to good. Clinical uses of the BLSS and additional studies are discussed.

PMID- 14692007
TI  - Therapists' adherence and competence and treatment discrimination in the NIDA
      Collaborative Cocaine Treatment Study.
AB  - The National Institute on Drug Abuse Collaborative Cocaine Treatment Study was
      designed to assess the efficacy of four different psychosocial interventions
      (cognitive therapy, supportive-expressive dynamic therapy, and individual and
      group drug counseling) for cocaine dependence. This report addresses the
      treatment integrity and discriminability of the three individual treatments.
      Therapists' adherence and competence for all three individual treatments during
      early and late sessions were rated reliably by three sets of independent expert
      judges (one set of expert clinicians for each treatment condition). Results
      indicated that therapists and counselors made use of the therapeutic techniques
      described in their respective treatment manuals rather than those from different
      treatment manuals. Thus, treatments were easily discriminable by the independent
      judges.

PMID- 14692008
TI  - A national survey of trainee impairment in clinical, counseling, and school
      psychology doctoral programs and internships.
AB  - The purpose of this study was to assess the frequency, type, and management of
      trainee impairment at a national level across doctoral programs in clinical,
      counseling, and school psychology and predoctoral internships. A total of 199
      surveys were completed, returned, and usable. In general, doctoral programs
      reported a greater frequency of trainee impairment than internships. However, a
      greater percentage of internships had a policy and program in place for managing
      impairments than did doctoral programs. These findings are compared with past
      studies and reviews of this issue. In light of these findings, specific
      implications for training programs are discussed, with the recommendation that
      training programs address more attention to the assessment and management of such
      problems.

PMID- 14692009
TI  - The relationship of sociotropy and autonomy to posttraumatic cognitions and PTSD
      symptomatology in trauma survivors.
AB  - The current study examined relationships between sociotropic and autonomous
      personality styles and posttraumatic stress disorder (PTSD) symptomatology
      following trauma as well as specific posttraumatic cognitions that have been
      shown to characterize individuals with PTSD. Self-report data were collected in a
      sample of 156 college students indicating a history of traumatic experience.
      Significant relationships were found between symptoms of PTSD and depression and
      measures of sociotropy, autonomy, and negative posttraumatic beliefs about self
      and world. Additionally, measures of autonomy and negative posttraumatic thoughts
      improved prediction of PTSD symptom level after controlling for depressive
      symptoms.

PMID- 14692010
TI  - Quantifying clinical judgment in the assessment of adolescent psychopathology:
      Reliability, validity, and factor structure of the Child Behavior Checklist for
      clinician report.
AB  - The aim of this study was to assess the reliability and validity of the Child
      Behavior Checklist (CBCL) as completed by doctoral-level clinicians in the
      treatment of adolescents. We asked 294 randomly selected, experienced
      psychiatrists and psychologists to describe a patient aged 14 to 18 in treatment
      for personality pathology. Clinicians completed the CBCL (parent-report version)
      and measures of adaptive functioning, personality pathology, and family and
      developmental history, which served as criterion variables to test the validity
      of the CBCL as completed by clinicians. Most CBCL scales demonstrated acceptable
      reliability. Validity estimates were impressive, and the data revealed clinically
      meaningful associations between specific CBCL scale scores and developmental and
      family history variables. Confirmatory factor analysis showed that the factorial
      structure of the clinician-report CBCL resembled that of the parent-report CBCL,
      with the exception of a substantially lower correlation between higher order
      internalizing and externalizing factors. The data suggest that clinical judgment
      can be both reliable and valid when quantified using psychometrically sound
      instruments.

PMID- 14692011
TI  - The Diagnostic Inventory for Depression: a self-report scale to diagnose DSM-IV
      major depressive disorder.
AB  - In this report from the Rhode Island Methods to Improve Diagnostic Assessment and
      Services (MIDAS) project, we describe the development and validation of the
      Diagnostic Inventory for Depression (DID), a new self-report scale designed to
      assess the Diagnostic and Statistical Manual of Mental Disorders, fourth edition
      (DSM-IV; American Psychiatric Association, 1994) symptom inclusion criteria for a
      major depressive episode, assess psychosocial impairment due to depression, and
      evaluate subjective quality of life. A large sample of 626 psychiatric
      outpatients completed the DID and were interviewed with the Structured Clinical
      Interview for DSM-IV (SCID). The measure's test-retest reliability, discriminant
      and convergent validity, and sensitivity to clinical change were investigated.
      The DID subscales achieved high levels of internal consistency and test-retest
      reliability. The DID was more highly correlated with another self-report measure
      of depression than with measures of anxiety, substance use problems, eating
      disorders, and somatization, thereby supporting the convergent and discriminant
      validity of the scale. The DID also was highly correlated with interviewer
      ratings of the severity of depression and psychosocial functioning, and DID
      symptom severity scores were significantly different in depressed patients with
      mild, moderate, and severe levels of depression. The DID was a valid measure of
      symptom change. Finally, the DID was significantly associated with a diagnosis of
      major depressive disorder.

PMID- 14692012
TI  - Remembering the 1978 and 1990 task forces on self-help therapies.
AB  - A special series on self-administered therapies was edited by Forrest R. Scogin
      for the Journal of Clinical Psychology (Volume 59, Number 3). Articles in the
      edited series failed to mention two task forces on self-help therapies that were
      sponsored by groups within the American Psychological Association in 1978 and
      1990. Consideration of the work by these task forces provides an historical
      perspective for the issues and recommendations provided in Scogin's series.

PMID- 14692014
TI  - A revised Spanish version of the Beck Depression Inventory: psychometric
      properties with a Puerto Rican sample of college students.
AB  - The Beck Depression Inventory (BDI) is a widely used self-report measure for
      depression. This study has two objectives: (a) to revise, develop, and adapt a
      Spanish language BDI (BDI-S) that takes the criteria for the diagnosis of major
      depression according to the DSM-IV into consideration; and (b) to evaluate the
      psychometric properties (internal reliability and construct validity) of the
      revised version of the BDI (BDI-S). A sample of 351 undergraduate students at the
      University of Puerto Rico participated in this study. The participants who agreed
      to participate in the study and signed the consent form completed self-report
      measures related to depression (BDI-S, CES-D, and LCSd-7), dysfunctional
      cognition (DAS-A and IBT), stressful life events (LES), and social support (CAS).
      The coefficient of internal consistency obtained for the 22 BDI-S items was.88.
      The correlation coefficients between the BDI-S and instruments that measured
      other constructs (not depression) were lower than the correlation coefficients
      between instruments that measured the same constructs. Factor analysis revealed
      that the factor loading for the BDI-S was congruent with dimensions of depression
      reported in the literature. These results generally support the internal
      consistency and the construct validity of the BDI-S.

PMID- 14692015
TI  - Progressive muscle relaxation, yoga stretching, and ABC relaxation theory.
AB  - This study compared the psychological effects of progressive muscle relaxation
      (PMR) and yoga stretching (hatha) exercises. Forty participants were randomly
      divided into two groups and taught PMR or yoga stretching exercises. Both groups
      practiced once a week for five weeks and were given the Smith Relaxation States
      Inventory before and after each session. As hypothesized, practitioners of PMR
      displayed higher levels of relaxation states (R-States) Physical Relaxation and
      Disengagement at Week 4 and higher levels of Mental Quiet and Joy as a
      posttraining aftereffect at Week 5. Contrary to what was hypothesized, groups did
      not display different levels of R-States Energized or Aware. Results suggest the
      value of supplementing traditional somatic conceptualizations of relaxation with
      the psychological approach embodied in ABC relaxation theory. Clinical and
      research implications are discussed.

PMID- 14692016
TI  - A historical note on false traumatic memories.
AB  - Unhampered by current ethical standards and human subject committees, H. Bernheim
      (1889) created a false memory of a horrific traumatic event. Bernheim also
      demonstrated his subject's willingness to discuss the implanted memory with a
      representative of the law. Bernheim's work represents the first documented case
      of an implanted false traumatic memory, with direct relevance to contemporary
      debates.

PMID- 14692017
TI  - The process for continuous improvement of the TNM classification.
AB  - The TNM classification is a worldwide benchmark for reporting the extent of
      malignant disease and is a major prognostic factor in predicting the outcome of
      patients with cancer. The objectives for cancer staging were defined by the
      International Union Against Cancer (UICC) TNM Committee almost 50 years ago and
      are still broadly applicable today. To keep pace with the modern demands of
      evidence-based practice, the UICC introduced a structured process for introducing
      changes to the TNM classification. The elements of the TNM process were
      determined to include the development of unambiguous criteria for the information
      and documentation required to consider changes in the classification,
      establishment of a well-defined process for the annual review of relevant
      literature, formation of site-specific expert panels, and the participation of
      experts from all over the world in the TNM review process. Communication between
      the oncology community and those involved in the TNM classification was
      established as being essential to the success of the process. The process, which
      was introduced in 2002, will be tested over the next 3-4 years and evaluated. In
      addition to the formal process, individual initiative, involvement by the
      national staging committees, and group consensus are required. Furthermore,
      increased involvement by the experts should improve the understanding and
      dissemination of the TNM classification.

PMID- 14692018
TI  - Increased risk of myelotoxicity in elderly patients with non-Hodgkin lymphoma.

PMID- 14692019
TI  - STK15/Aurora-A expression in primary breast tumors is correlated with nuclear
      grade but not with prognosis.
AB  - BACKGROUND: DNA amplification on chromosome 20q13 is commonly detected in breast
      carcinoma and is correlated with poor prognosis. STK15 maps to this amplicon. The
      objective of the current study was to use immunohistochemistry to determine STK15
      expression in primary breast tumors. The authors also explored whether STK15 was
      a prognostic factor for breast carcinoma by comparing the level of STK15 gene
      expression with clinical parameters that are known prognostic factors for the
      disease. METHODS: Archival mastectomy and lumpectomy specimens, randomly
      selected, were immunohistochemically stained to determine the STK15 gene
      expression level. The clinical parameters of these same patients were reviewed
      retrospectively and analyzed for correlations with STK15 expression level, based
      on a positive-versus-negative scoring system. RESULTS: Of the 112 human breast
      tumor specimens analyzed, 26% stained positively for STK15 by
      immunohistochemistry. Of the tumors, that stained positively 62.1% had a well-to
      moderately differentiated nuclear grade. The correlation between STK15 staining
      and nuclear grade was nearly statistically significant (P = 0.05). No association
      was found between STK15 staining and tumor size, lymph node status, or hormone
      receptor status. Analysis of recurrence-free survival and overall survival rates
      also failed to reveal a statistically significant difference between the two
      groups. CONCLUSIONS: STK15 expression by immunohistochemistry was noted in
      approximately one-fourth of primary breast tumors. STK15 expression was
      associated with nuclear grade, but no correlation was found between the other
      clinical parameters evaluated. Furthermore, no differences were found in survival
      rates when they were analyzed by level of STK15 staining.

PMID- 14692020
TI  - Correlation of tumor volume and surface area with lymph node status in patients
      with multifocal/multicentric breast carcinoma.
AB  - BACKGROUND: Multicentric breast carcinomas have a higher frequency of axillary
      lymph node metastasis than unifocal tumors of similar stage. It remains unclear
      whether this merely reflects larger tumor volumes or a different biologic
      behavior. The authors have shown previously that when aggregate tumor diameter
      are used for staging, unifocal and multifocal tumors have a similar frequency of
      axillary lymph node metastasis. However, summing diameter overestimates actual
      tumor volume because volume is proportional to the third power of the diameter.
      Therefore, the aim of the current study was to reanalyze the relation between
      size and axillary lymph node status by correcting for tumor volumes and surface
      areas. METHODS: Volumes and surface areas of 122 breast tumor specimens with
      multiple macroscopic nodules (two foci: n = 95; three foci: n = 22; three foci: n
      = 5) were calculated by approximating the shape of each tumor nodule to an
      ellipsoid (for volume) or to a prolate spheroid (for area). For comparison, the
      authors used an internal control series, comprised of 469 macroscopic unifocal
      tumors. For all patients, multiple assessments of largest tumor size and combined
      size of all foci were correlated with the status of axillary lymph nodes. The
      associations between lymph node status, tumor volume or area, and multifocality
      were modeled using univariate and multivariate logistic regression. RESULTS: When
      either the largest or the aggregate tumor volume was used as a size estimate,
      tumor specimens with multiple nodules had a higher frequency of lymph node
      involvement compared with unifocal tumors of a similar volume or area. The odds
      ratio (OR) for having positive lymph nodes was 2.34 for aggregate volume
      measurement (P < 0.001). Surface area estimates yielded similar results (OR =
      2.2, P < 0.001). CONCLUSIONS: Breast tumors with multiple macroscopic nodules had
      a different biology, with a propensity to dissemination at smaller tumor volumes
      (i.e., there was another factor besides volume alone that accounted for the
      differences in behavior).

PMID- 14692021
TI  - Uncertain benefit from surgery in patients with lung metastases from breast
      carcinoma.
AB  - BACKGROUND: Isolated lung metastases have been reported to occur in 10-20% of all
      women with breast carcinoma. The authors described a series of patients who
      underwent surgery for lung metastases from breast carcinoma. METHODS: They
      reviewed the files of 125 consecutive patients who underwent surgery with a
      curative intent for lung metastases from breast carcinoma between 1972 an 1998 at
      a single institution. Survival curves were plotted by the Kaplan-Meier method.
      Prognostic factors were identified using the log-rank test and a Cox proportional
      hazards model for univariate and multivariate analyses, respectively. RESULTS:
      The median age at surgery was 53 years. There was a median of 1 resected
      metastasis (range, 1-16 resected metastases). The median size of the largest
      metastasis was 19 mm (range, 5-70 mm). The median disease-free interval (DFI) was
      3 years. The median follow-up time after surgery was 8.5 years (range, 25 days to
      22 years). The 3-year, 5-year, and 10-year probabilities of survival were 58%
      (95% confidence interval [95% CI], 49-67%), 45% (95% CI, 36-55%), and 30% (95%
      CI, 21-41%), respectively. The median survival time after surgery was 4.2 years.
      Complete resection was achieved in 96 patients. The quality of the resection
      (complete vs. incomplete) was not a statistically significant prognostic factor
      by univariate analysis and there was no significant difference between these two
      groups in terms of adjuvant postoperative therapy. The characteristics of the
      primary tumor and the number of metastases (one vs. two or more) had no
      detectable influence on survival. The size of the largest metastasis (> 20 mm or
      < or = 20 mm) and the DFI (< or = 3 years vs. > 3 years) were highly significant
      prognostic factors (P = 0.006 and P = 0.003, respectively). This was confirmed by
      multivariate analysis. Patients with a DFI < or = 3 years and/or the largest
      metastasis > 20 mm reportedly had a poor outcome (median survival, 2.6 years vs.
      8.5 years for patients with none of these poor prognostic factors). CONCLUSIONS:
      Resection of lung metastases from breast carcinoma was associated with a
      significant 5-year survival rate of 45%. Whether these encouraging findings
      resulted from the surgical procedure itself or the preoperative selection of
      patients remained uncertain. When surgery is considered in this setting, the size
      of the largest metastasis and the DFI should be taken into account.

PMID- 14692022
TI  - Zoledronic acid is superior to pamidronate for the treatment of bone metastases
      in breast carcinoma patients with at least one osteolytic lesion.
AB  - BACKGROUND: Treatment with zoledronic acid (Zol) was compared with a dose of 90
      mg of pamidronate (Pam) in breast carcinoma (BC) patients with at least 1
      osteolytic lesion based on data from a Phase III, randomized trial. METHODS:
      Overall, 1130 patients with breast carcinoma who had all types of bone metastases
      (osteolytic, mixed, or osteoblastic by radiology) were randomized to receive
      treatment with either 4 mg of Zol or 8 mg of Zol as a 15-minute infusion or 90 mg
      of Pam as a 2-hour infusion every 3-4 weeks for 12 months. A skeletal-related
      event (SRE) was defined as a pathologic fracture, spinal cord compression,
      radiotherapy, or surgery to bone. RESULTS: Among all patients with BC, the
      proportion of those who had an SRE (primary endpoint) was comparable between
      treatment groups (43% of patients who received 4 mg of Zol vs. 45% of patients
      who received Pam). Among patients who had breast carcinoma with at least 1
      osteolytic lesion (n = 528 patients), the proportion with an SRE was lower in the
      4-mg Zol group compared with the Pam group (48% vs. 58%), but this did not reach
      statistical significance (P = 0.058). The time to first SRE was significantly
      longer in the 4-mg Zol group compared with the Pam group (median, 310 vs. 174
      days; P = 0.013). Moreover, multiple-event analysis demonstrated significant
      further reductions in the risk of developing SREs over the reduction achieved
      with Pam (30% in the osteolytic subset [P = 0.010] and 20% for all patients with
      BC [P = 0.037]). CONCLUSIONS: The current data indicate that treatment with 4 mg
      of Zol was more effective than 90 mg of Pam in reducing skeletal complications in
      a subset of patients with breast carcinoma who had at least 1 osteolytic lesion
      at study entry.

PMID- 14692023
TI  - Is breast cancer survival improving?
AB  - BACKGROUND: Despite advances in therapies for breast cancer, improvement in
      survival for patients with recurrent or metastatic breast cancer has been
      difficult to establish. The objective of the current study was to determine
      whether the survival of women with recurrent breast cancer has improved from 1974
      to 2000. METHODS: The authors analyzed the survival experience of 834 women who
      developed recurrent breast cancer between November 1974 and December 2000. All
      patients had been treated previously with adjuvant anthracycline-based protocols.
      Patients were divided into five consecutive groups based on year of breast cancer
      recurrence, and survival was compared across the five groups. Because some
      prognostic variables were divided unevenly divided among the cohorts, a
      multivariate model was created to determine the association of year of recurrence
      and survival after accounting for other prognostic factors. RESULTS: In the
      unadjusted analysis, there was a statistically significant improvement in
      survival across the five groups, and the more recent cohorts had longer survival
      (P < 0.001). Other variables that predicted longer survival after breast cancer
      recurrence included smaller initial tumor size, lower stage of disease, fewer
      lymph nodes involved, longer disease-free interval, estrogen receptor-positive
      tumors, and nonvisceral dominant site of disease recurrence. In the multivariate
      analysis, which adjusted for these prognostic factors, year of recurrence was
      associated with a trend toward improved survival, with a 1% reduction in risk for
      each increasing year. CONCLUSIONS: For these cohorts of patients, the authors
      present data suggesting that the prognosis for patients with recurrent breast
      cancer improved between 1974 and 2000.

PMID- 14692024
TI  - Hereditary nonpolyposis colorectal carcinoma (HNPCC) and HNPCC-like families:
      Problems in diagnosis, surveillance, and management.
AB  - BACKGROUND: To the authors' knowledge, hereditary nonpolyposis colorectal
      carcinoma (HNPCC) is the most commonly occurring hereditary disorder that
      predisposes to colorectal carcinoma (CRC), accounting for approximately 2-7% of
      all CRC cases diagnosed in the U.S each year. Its diagnosis is wholly dependent
      on a meticulously obtained family history of cancer of all anatomic sites, with
      particular attention to the pattern of cancer distribution within the family.
      METHODS: The objective of the current study was to illustrate various vexing
      problems that can deter the diagnosis of HNPCC and, ultimately, its management.
      This was an observational cohort study. Sixteen HNPCC and HNPCC-like families
      were selected from a large resource of highly extended HNPCC families. High-risk
      patients were selected from these HNPCC families. An ascertainment bias was
      imposed by the lack of a population-based data set. Personal interviews and
      questionnaires were used for data collection. RESULTS: There was an array of
      difficulties highlighted by limitations in compliance, lack of a clinical or
      molecular basis for an HNPCC diagnosis, ambiguous DNA findings, problems in
      genetic counseling, failure to meet Amsterdam or Bethesda criteria, small
      families, lack of medical and pathologic documentation, poor cooperation of
      family members and/or their physicians, cultural barriers, economic stress,
      frequent patient fear and anxiety, perception of insurance discrimination, and
      limited patient and/or physician knowledge regarding hereditary cancer.
      CONCLUSIONS: The diagnosis and management of HNPCC is predicated on physician
      knowledge of its phenotypic and genotypic heterogeneity, in concert with the
      multifaceted problems that impact on patient compliance.

PMID- 14692025
TI  - A Phase II trial of suramin monthly x 3 for hormone-refractory prostate
      carcinoma.
AB  - BACKGROUND: The goal of the current study was to determine the prostate-specific
      antigen (PSA) and objective response rates and the pharmacokinetics associated
      with a monthly x 3 one-hour infusion of suramin in 58 patients with hormone
      refractory prostate carcinoma. METHODS: A PSA response was defined as a > 50%
      reduction in the PSA level from baseline for at least 3 consecutive evaluations
      over a minimum of 6 weeks. The suramin dose was 2400 mg/m(2) taken intravenously
      on Day 1, 1620 mg/m(2) on Day 29, and 1292 mg/m(2) on Day 57. All patients
      received 0.5 mg dexamethasone twice daily. RESULTS: Among 56 evaluable patients
      (median entry PSA level, 229.5 ng/mL), there were 21 PSA responders (37.5%).
      Among 27 patients with measurable disease, there were 5 responders (4 partial and
      1 complete). The median overall survival time was 15.3 months. Grade III fatigue
      (14.1%) was the predominant toxicity observed. Suramin plasma levels remained
      high even 3 months after treatment was discontinued. Among the 12 evaluable
      patients who previously had received chemotherapy, the PSA response rate was 42%;
      one response was observed among 4 patients with measurable disease, and the
      median survival was 12 months. CONCLUSIONS: Monthly bolus suramin was well
      tolerated, reduced PSA levels, and induced objective responses, even in patients
      who previously had received chemotherapy.

PMID- 14692026
TI  - Is there age bias in the treatment of localized prostate carcinoma?
AB  - BACKGROUND: Treatment recommendations for localized prostate carcinoma are based
      on the patient's remaining life expectancy (RLE), which is influenced by age,
      comorbidity, and tumor grade. Previous studies have evaluated the influence of
      age and comorbidity, but to the authors' knowledge not RLE, on actual treatment
      decisions. METHODS: An age-stratified random sample of 347 patients was generated
      from a cohort of all patients with newly diagnosed prostate carcinoma in the
      Ontario Cancer Registry between May 1, 1995 and April 30, 1996 (n = 5192). Chart
      review was performed to obtain detailed tumor, comorbidity, and treatment
      information. RLE was estimated from a published model derived from a cohort of
      451 men with untreated prostate carcinoma who were followed for 15 years.
      Multivariable logistic regression was performed to evaluate predictors of
      treatment, such as radical prostatectomy (RP), radiotherapy (RT), or potentially
      curative therapy (RP or RT), in relation to patient age, comorbidity, tumor
      characteristics, and RLE. RESULTS: RP was provided within 6 months of diagnosis
      to 58.7%, 32.1%, 2.6%, and 0% of patients of ages < 60 years, 60-69 years, 70-79
      years, and 80+ years, respectively. The results for RT were 6.4%, 30.9%, 23.4%,
      and 3.3%, respectively. Increasing comorbidity decreased rates of RP but did not
      affect use of RT. After controlling for comorbidity and tumor characteristics,
      older men were found to be treated with RP less often than younger men with
      similar RLE, whereas RLE did not appear to influence receipt of RT. CONCLUSIONS:
      Although different mechanisms may account for these results, an age bias may be
      present among urologists and radiation oncologists treating men with localized
      prostate carcinoma.

PMID- 14692027
TI  - Platinum-free combination chemotherapy in patients with advanced or metastatic
      transitional cell carcinoma.
AB  - BACKGROUND: Platinum-based regimens have improved response rates and survival in
      patients with advanced transitional cell carcinoma (TCC) of the urothelial tract.
      However, the toxicities of platinum-based chemotherapy are considerable. Regimens
      with reduced toxicity that are applicable to a broader group of TCC patients
      without sacrificing activity therefore are of interest. METHODS: Because
      gemcitabine, paclitaxel, and methotrexate have each been reported to possess
      single-agent activity in this disease, the authors evaluated the tolerability and
      efficacy of fixed doses of paclitaxel (100 mg/m(2) over 3 hours) and methotrexate
      (30 mg/m(2)) with escalating doses of gemcitabine (800-1000 mg/m(2)), all given
      on Days 1 and 8 every 21 days, in patients with previously untreated unresectable
      or metastatic TCC. RESULTS: Twenty-five patients were enrolled. Two patients were
      ineligible and were excluded from analysis. Because no dose-limiting toxicity
      occurred in the first 4 patients who were given gemcitabine at a dose of 800
      mg/m(2), the gemcitabine dose was escalated to 1000 mg/m(2) in the next 21
      patients. Of the 21 patients assessable for response, 6 had achieved a complete
      response (CR) and 6 had achieved a partial response, for an overall response rate
      of 57%. An additional patient was converted to a CR surgically. The median
      overall and progression-free survival times were 18 months and 9.2 months,
      respectively. Toxicity was predominantly neutropenia: Grade 3 in 9 patients (39%)
      and Grade 4 in 4 patients (17%) (according to the Southwest Oncology Group
      Toxicity Criteria, version 12/1994). One patient died of septic shock associated
      with febrile neutropenia after three cycles. CONCLUSIONS: The regimen of
      gemcitabine, paclitaxel, and methotrexate at this dose and schedule was found to
      possess activity in patients with locally advanced or metastatic TCC. Further
      studies of this regimen are warranted.

PMID- 14692028
TI  - Surgical treatment of recurrent endometrial carcinoma.
AB  - BACKGROUND: Surgery does not have a definite role in the treatment of patients
      with recurrent endometrial carcinoma, except for those with central pelvic
      recurrences. The authors describe their experience with surgery in patients with
      abdominal endometrial recurrences. METHODS: Between 1988 and 2000, 75 patients
      with abdominal and pelvic endometrial recurrences underwent secondary rescue
      surgery. Patients were classified according to the presence or absence of
      residual tumor after surgery. Therapy after rescue surgery was undertaken at the
      discretion of the medical oncologist. The progression-free interval and overall
      survival were defined as the time from secondary rescue surgery to the specific
      event and were evaluated by the Kaplan-Meier method and the log-rank test. A Cox
      proportional hazards regression model was used to compare survival with
      covariates. RESULTS: Fifty-six patients (74.7%) underwent optimal debulking.
      Major surgical complications were observed in 23 patients (30.7%). Only 1
      postoperative death was observed, although the mortality rate for surgical
      complications after the postoperative period was 8%. Patients who underwent
      optimal debulking had a significantly better cumulative survival rate compared
      with patients who had residual disease (36% vs. 0% at 60 months; P < 0.05).
      Residual disease, chemotherapy after rescue surgery, and central pelvis-vagina as
      the only site of recurrence were associated significantly with survival.
      CONCLUSIONS: The authors found that this approach was very challenging in terms
      of the procedures involved, the incidence of major surgical complications, and
      the high mortality rate. It was useful in increasing overall survival, provided
      that patients were free of macroscopic disease. Careful selection of patients is
      needed to minimize mortality.

PMID- 14692029
TI  - Early-stage cervical carcinoma, radical hysterectomy, and sexual function. A
      longitudinal study.
AB  - BACKGROUND: Limited knowledge exists concerning the impact of radical
      hysterectomy (RH) alone on the sexual function of patients with early-stage
      cervical carcinoma. The authors investigated the longitudinal course of self
      reported sexual function after RH. METHODS: The current study was comprised of
      173 patients with lymph node-negative, early-stage cervical carcinoma who had
      undergone RH and pelvic lymphadenectomy. They were assessed prospectively using a
      validated self-assessment questionnaire 5 weeks and 3 months, 6 months, 12
      months, 18 months, and 24 months after RH. Results were compared with an age
      matched control group from the general population. RESULTS: Compared with control
      women, patients experienced severe orgasmic problems and uncomfortable sexual
      intercourse due to a reduced vaginal size during the first 6 months after RH,
      severe dyspareunia during the first 3 months, and sexual dissatisfaction during
      the 5 weeks after RH. A persistent lack of sexual interest and lubrication were
      reported throughout the first 2 years after RH. Long-term lack of sexual interest
      and insufficient vaginal lubrication were confirmed by the patient's self
      reported changes 12 months after RH compared with before the cancer diagnosis and
      by a pre-post comparison within patients. However, most of the patients who were
      sexually active before their cancer diagnosis were sexually active again 12
      months after surgery (91%), although with a decrease in sexual frequency
      reported. CONCLUSIONS: RH had a persistent and negative impact on patients'
      sexual interest and vaginal lubrication whereas the majority of other sexual and
      vaginal problems disappeared over time. Sexual and vaginal problems in the short
      term and long-term after RH should be discussed with the patient before and after
      surgery.

PMID- 14692030
TI  - Splenic and nodal marginal zone lymphomas are indolent disorders at high
      hepatitis C virus seroprevalence with distinct presenting features but similar
      morphologic and phenotypic profiles.
AB  - BACKGROUND: Splenic and nodal marginal zone lymphomas (MZL) are subtypes of
      marginal zone-derived neoplasms. Due to their rarity, little is known concerning
      their relation, pattern of dissemination, and treatment outcome. METHODS: The
      authors analyzed the clinicopathologic features and outcome of 43 patients (34
      patients with splenic MZL and 9 patients with nodal MZL). All lesional tissues
      obtained at diagnosis were reviewed histologically. RESULTS: Among the patients
      with splenic MZL, 30 patients had Stage IV disease (based on the Ann Arbor
      staging system). Twenty-six patients presented with splenomegaly with or without
      limited involvement of abdominal lymph nodes, whereas 7 patients showed disease
      extension to superficial lymph nodes. Hepatitis C virus (HCV) serology was
      positive in 35% of patients. Seventeen patients underwent splenectomy, 8 patients
      received chemotherapy, and 7 patients were followed without initial treatment.
      Interferon produced a lymphoma response in three of four HCV positive patients.
      Of 27 treated patients, 13 patients achieved a complete response, and 12 patients
      achieved a partial response. The median event-free survival (EFS) was 3.3 years
      (5.1 years for patients with disease confined to the abdomen and 2.1 years for
      patients with disease extension to superficial lymph nodes). Among nine patients
      with nodal MZL, four patients had Stage IV disease. HCV serology was positive in
      two patients. Five patients responded to chemotherapy. The median EFS was 2.8
      years. The median overall survival was not reached for patients with both types
      of MZL. CONCLUSIONS: The results of the current study demonstrated that splenic
      and nodal MZL are indolent lymphomas with different presenting features but
      common morphologic and biologic characteristics, including high HCV
      seroprevalence. Studies will be required to identify specific biologic markers
      and to define the best treatment.

PMID- 14692031
TI  - The significance of myelosuppression during therapy with imatinib mesylate in
      patients with chronic myelogenous leukemia in chronic phase.
AB  - BACKGROUND: Imatinib mesylate induces high rates of hematologic and cytogenetic
      response in patients with chronic myelogenous leukemia (CML). During therapy with
      imatinib, up to 45% of patients with CML reportedly experience myelosuppression >
      or = Grade 3, requiring interruption of therapy and/or dose reductions. The
      significance of myelosuppression for response to imatinib is unknown. METHODS:
      The authors analyzed 143 patients with late chronic-phase CML who were treated
      with imatinib after failing interferon. Univariate and multivariate analyses were
      performed to determine patient characteristics that were correlated with
      myelosuppression response and the association between myelosuppression and
      cytogenetic response. RESULTS: Neutropenia > or = Grade 3 (according to National
      Cancer Institute Common Toxicity Criteria) occurred in 64 patients (45%), and
      thrombocytopenia > or = Grade 3 occurred in 31 patients (22%). Any
      myelosuppression > or = Grade 3 was associated with a lower rate of major (P =
      0.04) or complete (P = 0.01) cytogenetic responses. This was more pronounced with
      myelosuppression that lasted > 2 weeks. The major cytogenetic response rate was
      58% with Grade > or = 3 myelosuppression compared with a rate of 75% without
      Grade > or =3 myelosuppression (P = 0.03); the complete cytogenetic response
      rates were 36% and 63%, respectively (P = 0.001). In a multivariate analysis,
      pretreatment platelet count, imatinib dose reductions, and duration of
      myelosuppression were associated significantly with response. CONCLUSIONS:
      Myelosuppression is an independent adverse factor for achieving cytogenetic
      response with imatinib in patients with CML. Intervention with hematopoietic
      growth factors in patients with CML who are treated with imatinib should be
      investigated.

PMID- 14692032
TI  - Prolonged survival after complete resection of metastases from intraocular
      melanoma.
AB  - BACKGROUND: The median survival time is only 2-6 months after a diagnosis of
      metastases from intraocular melanoma. Because complete resection of metastatic
      melanoma from a cutaneous primary tumor can prolong survival, the authors
      hypothesized that resection also might benefit patients with metastases from an
      intraocular site. METHODS: From 1971 to 1999, 112 patients with metastatic
      melanoma from an intraocular site were enrolled in various treatment protocols
      after informed consent was obtained. Prospectively recorded clinical variables
      and follow-up information were retrieved from the patient database. Survival
      curves were estimated using the Kaplan-Meier method. Univariate analysis was
      performed with the log-rank test. Multivariate analysis was performed using the
      Cox proportional hazards regression model. Propensity score analysis was used to
      reduce the imbalance between subgroups and to assess treatment effect. RESULTS:
      Seventy-eight patients (70%) presented with liver involvement. Twenty-four
      patients (21%) underwent resection of metastatic lesions. At a median follow-up
      time of 11 months (range, 1-97 months; > 36 months for survivors), the median
      survival period was 11 months and the 5-year survival rate was 7%. Univariate
      analysis showed that surgical resection, site of metastases, number of metastatic
      lesions, and disease-free interval were correlated significantly with survival (P
      < 0.001, P < 0.001, P < 0.001, and P = 0.031, respectively). Multivariate
      analysis showed that surgical resection was significant (P = 0.008) but that the
      site of metastases was not (P = 0.146). The median survival and the 5-year
      survival rate were 38 months and 39%, respectively, for surgical patients, versus
      9 months and 0%, respectively, for nonsurgical patients. After adjusting for
      covariate imbalance by propensity score analysis, surgery remained significant (P
      = 0.021) on multivariate analysis. CONCLUSIONS: Complete resection may prolong
      survival in certain patients with distant metastases from intraocular primary
      melanoma. However, the overall unfavorable prognosis indicates an urgent need for
      more effective nonsurgical interventions.

PMID- 14692033
TI  - Association of nonmelanoma skin cancer with second malignancy.
AB  - BACKGROUND: Heightened risks of second cancers have been reported in patients
      with nonmelanoma cancer of the skin (NMSC), but this association has not been
      studied in a large, ethnically diverse, multigeographic population. METHODS: This
      cross-sectional study assessed the association of NMSC with another malignancy in
      the Women's Health Initiative Observational Study, a study that was conducted in
      40 communities throughout the U.S. and involved 93,676 postmenopausal women ages
      50-79 years. Cancer history, demographics, and previous and current risk
      exposures were determined by questionnaire at a baseline examination. Logistic
      regression was used to assess the association (odds ratio) of a history of NMSC
      with a history of other (non-NMSC) cancers controlling for age and potential
      confounding factors. Complete cancer data were available in 92,658 women.
      RESULTS: In age-adjusted analyses, women with a history of NMSC (n = 7554 women)
      were 2.30 times as likely to report a history of another cancer, other than NMSC,
      compared with women who had no history of NMSC (95% confidence interval [95% CI],
      2.18-2.44). In a subgroup analysis, black women with NMSC had 7.46 times the odds
      (95% CI, 3.08-18.0) of reporting a second malignancy compared with black women
      without NMSC. CONCLUSIONS: This study provides additional evidence of an
      association between NMSC and another malignancy in a large, multiethnic
      population.

PMID- 14692034
TI  - Screening mammography performance and cancer detection among black women and
      white women in community practice.
AB  - BACKGROUND: Despite improvement in mammography screening attendance, black women
      continue to have poorer prognosis at diagnosis than white woman. Data from the
      Carolina Mammography Registry were used to evaluate whether there may be
      differences in mammography performance or detected cancers when comparing black
      women with white women who are screened by mammography. METHODS: Prospectively
      collected data from community-based mammography facilities on 468,484 screening
      mammograms (79,397 in black women and 389,087 in white women) were included for
      study. Mammograms were linked to a pathology data base for identification of
      cancers. Sensitivity, specificity, positive predictive value, and cancer
      detection rates were compared between black women and white women. Logistic
      regression methods were used to control for covariates associated with
      performance characteristics. Differences in cancer characteristics were compared
      between black women and white women using chi-square statistics. RESULTS:
      Screening mammography performance results for black women compared with white
      women were as follows: sensitivity, odds ratio (OR) = 1.07 (95% confidence
      interval [95% CI], 0.83-1.39); specificity, OR = 1.02 (95% CI, 0.98-1.06); and
      positive predictive value, OR = 1.07 (95% CI, 0.94-1.23). Among women with no
      previous screening, black women had a larger proportion of invasive tumors that
      measured > or = 2 cm (38% vs. 26%; P = 0.04). The cancer detection rate was
      highest among black women who reported symptoms at screening (13.9 per 1000 black
      women vs. 7.9 per 1000 white women). Invasive cancers in black women were poorer
      grade (P = 0.001), and more often had negative estrogen receptor status and
      progesterone receptor status (P < 0.001). CONCLUSIONS: Overall, screening
      mammography performed equally well in black women and white women controlling for
      age, breast density, and time since previous mammogram. Black women who reported
      symptoms had larger and higher grade tumors compared with white women.
      Educational efforts need to be strengthened to encourage black women to react
      sooner to symptoms, so that the tumors detected will be smaller and black women
      will have a better prognosis when they appear for mammography.

PMID- 14692035
TI  - Long-term risk of malignant neoplasm associated with gestational glucose
      intolerance.
AB  - BACKGROUND: Previous studies have demonstrated an association between diabetes
      mellitus and cancer risk. However to the author's knowledge, no data regarding
      the risk of cancer associated with subclinical impaired glucose tolerance have
      been published to date. An association between various types of cancer and any
      continuum of risk across the spectrum of glucose tolerance may be important in
      determining the nature of the association between diabetes mellitus and the risk
      of malignancy. METHODS: The current study was conducted to examine the long-term
      risk of malignant neoplasms associated with maternal glucose intolerance. A 20
      year follow-up study of a cohort of women who had previously taken part in a
      study in 1980 that investigated maternal glucose metabolism and fetal outcome was
      performed. Gestational glucose metabolism, smoking behavior, and weight and
      height measured at the time of index pregnancy, as well as weight, height, and
      smoking behavior assessed by questionnaire in 1999, were examined. The main
      endpoint of the study was hospital admission with a diagnosis of malignant
      neoplasm as ascertained by linkage data. RESULTS: Thirty-four of the 753 women
      living in Grampian (4.5%) were admitted to the hospital with a diagnosis of
      malignant neoplasm; of these, 18 cases were malignant neoplasms of the breast.
      After adjustment for known risk factors, both malignant neoplasm and malignant
      neoplasm of the breast were found to be significantly associated with gestational
      glucose intolerance. CONCLUSIONS: Subclinical glucose intolerance during
      pregnancy was found to be associated with a dose-related increase in the risk of
      malignant neoplasm, particularly malignant neoplasm of the breast.

PMID- 14692036
TI  - Ethnic/racial influences on the physiologic health of cancer survivors.
AB  - BACKGROUND: Improvements in early detection, treatment, and general supportive
      care allow more people to survive cancer. Information regarding the long-term
      health impact of cancer and cancer treatments on these survivors of adult-onset
      malignancies is gradually accumulating. Although information is limited overall,
      it is apparent that the cancer experience differs across ethnically/racially
      diverse populations. METHODS: In the current report, the authors characterized
      and compared health profiles among ethnic/racial groups within a large cohort (n
      > 6000) of long-term survivors of cancer. In addition, the authors focused on
      survivors of cervical carcinoma, because they constitute a substantial and
      relatively homogeneous portion of the overall cohort. RESULTS: The authors
      observed significant differences among African American, Hispanic American, and
      Caucasian American cancer survivors in terms of age at diagnosis, time since
      diagnosis, family dynamics, education, type of malignancy, and perceived
      influences of cancer on specific physiologic health problems. Among survivors of
      cervical carcinoma, there were significant ethnic/racial differences in terms of
      disease histology as well as the impact of the disease on overall health.
      CONCLUSIONS: The current study reveals significant ethnic/racial differences
      among cancer survivors and highlights the need for further investigation of the
      relation between cancer survivorship and ethnicity/race.

PMID- 14692037
TI  - The significance of isolation of saprophytic molds from the lower respiratory
      tract in patients with cancer.
AB  - BACKGROUND: Invasive infections caused by molds other than Aspergillus, Fusarium,
      and Zygomycetes have been reported sporadically in patients with leukemia and
      allogeneic bone marrow transplantation (BMT). However, the significance of lower
      respiratory tract cultures that are positive for these saprophytic molds in an
      unselected population of patients with cancer remains unclear. METHODS: The
      authors evaluated the significance of respiratory specimens positive for
      saprophytic molds in patients with cancer using the criteria set by the European
      Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group
      (MSG). They included the diagnostic category of indeterminate pulmonary invasive
      mold infection (IMI) for cases that met the criteria for probable IMI but had
      other pathogens concomitantly isolated from the respiratory tract. RESULTS:
      Eighty-five cases with at least 1 positive culture were identified in 79
      patients. Two cases were proven IMI, 29 were indeterminate IMI, 5 were possible
      IMI, and 49 were no IMI. All 38 cases from patients with solid tumors represented
      colonization compared with only 11 of the 47 cases (23%) from high-risk patients
      (P < 0.0001). The positive predictive value (PPV) of cultures was 0% in patients
      with solid tumors and ranged from 4.3% to 76.6%, depending on the analytic model
      used, in high-risk patients with leukemia and recipients of BMT. Cultures
      positive for Scedosporium spp. had a higher PPV (9.1-100%) than did cultures
      positive for non- Scedosporium spp. (2.8- 69.4%). CONCLUSIONS: Adjustments of the
      EORTC/MSG criteria may be required for the diagnosis of invasive infections
      caused by saprophytic molds, especially non-Scedosporium spp., in patients with
      cancer.

PMID- 14692038
TI  - Rare ductal adenocarcinoma of the pancreas in patients younger than age 40 years.
AB  - BACKGROUND: Pancreatic ductal adenocarcinomas (PDACs) are extremely rare before
      age 40 years. The objective of the current study was to determine whether the
      features of PDACs in patients age < 40 years differ from those in older patients.
      The authors reviewed the literature and their own files. METHODS: The cases
      reported in the literature were evaluated to determine their precise diagnoses
      and characteristic features. In a series of 439 PDACs from the authors' files,
      tumors in patients age < 40 years were identified, and their clinicopathologic
      features and certain genetic features were compared with those in a selected
      group of patients age > 40 years. RESULTS: Of 71 pancreatic carcinomas reported
      in patients age < 40 years, only 20 fully qualified as PDACs. The remaining
      tumors represented malignancies other than PDACs, such as pancreatoblastoma,
      solid-pseudopapillary neoplasms, acinar cell carcinomas, and endocrine tumors.
      PDACs in patients age < 20 years were the absolute exception and commonly were
      associated with risk factors such as Peutz-Jeghers syndrome, hereditary
      pancreatic cancer syndrome, and preceding radiotherapy. In the authors' series of
      patients, there were 6 PDACs and 4 PDAC variants in patients age < 40 years
      (0.2%), all in male patients. These tumors compared well with the PDACs in
      patients age > 40 years in their pathologic and molecular findings. Three
      patients were age < or = 20 years, and 2 of those patients had a mucinous
      component with MUC2 positivity. CONCLUSIONS: The incidence of PDACs in patients
      age < 40 years was approximately 0.3%, and the incidence in patients age < 20
      years was 0.1%. Their clinicopathologic findings were comparable to those in
      patients age > 40 years, but they seemed to include more variants, particularly
      mucinous carcinomas. In addition, PDACs in younger patients frequently appeared
      to be associated with genetic factors.

PMID- 14692039
TI  - Suicidality in terminally ill Japanese patients with cancer.
AB  - BACKGROUND: The risk of suicide is higher in patients with cancer than in the
      general population, making end-of-life care of suicidal terminal patients with
      cancer critical. To identify factors and longitudinal changes associated with
      suicidality among terminally ill Japanese patients with cancer, a prospective
      cohort study was performed. METHODS: Consecutive outpatients with cancer who
      registered with a palliative care unit participated. Structured interviews (e.g.,
      Structured Clinical Interview for DSM- III-R [SCID]) were conducted to assess
      patient suicidal ideation (Ideation) and interest in requesting euthanasia
      (Interest) as main outcome measures of suicidality. Possible correlated factors
      also were investigated. The authors analyzed the data from 140 terminally ill
      patients with cancer at initial study participation (baseline) whose subsequent
      survival time was < 6 months. Of these 140 patients, 57 (40.7%) completed the
      follow-up assessment after admission to the unit. RESULTS: At baseline, 8.6% of
      the patients had Ideation and 5.0% had Interest. Self-reported anxiety and
      depression was significantly associated with Ideation (P= 0.003). Changes in
      Ideation and Interest occurred in 38.6% and 15.8% of the patients, respectively.
      Ideation was more likely to change than Interest (P = 0.006). The current study
      did not identify factors that predict changes and occurrences of suicidal
      ideation and interest in requesting euthanasia. CONCLUSIONS: Suicidality can
      change even in terminally ill patients. End-of-life care that focuses on the
      psychologic distress of dying individuals may be a way of preventing suicide.

PMID- 14692040
TI  - Cognitive-behavioral stress management improves stress-management skills and
      quality of life in men recovering from treatment of prostate carcinoma.
AB  - BACKGROUND: The current study evaluated the efficacy of a 10-week, group-based,
      cognitive-behavioral stress management (CBSM) intervention relative to a half-day
      seminar in improving quality of life (QoL) among men who were treated for
      localized prostate carcinoma (PC) with either radical prostatectomy (RP) or
      radiation therapy. METHODS: Ninety-two men were assigned randomly to either the
      10-week CBSM group intervention or a 1-day seminar (control group). The
      intervention was designed to improve QoL by helping participants to identify and
      effectively manage stressful experiences and was focused on the treatment-related
      sequelae of PC. RESULTS: A hierarchical regression model was used to predict
      postintervention QoL. The final model, including all predictors and relevant
      covariates (i.e., income, baseline QoL, ethnicity, and group condition),
      explained 62.1% of the variance in QoL scores. Group assignment was a significant
      predictor (beta = - 0.14; P = 0.03) of QoL after the 10-week intervention period,
      even after controlling for ethnicity, income, and baseline QoL. Post-hoc analyses
      revealed that individuals in the CBSM intervention condition showed significant
      improvements in QoL relative to men in the 1-day control seminar. Improved QoL
      was mediated by greater perceived stress-management skill. CONCLUSIONS: A 10-week
      cognitive-behavioral group intervention was effective in improving the QoL in men
      treated for PC, and these changes were associated significantly with intervention
      associated increases in perceived stress-management skills.

PMID- 14692041
TI  - Antiangiogenic activity of genistein in pancreatic carcinoma cells is mediated by
      the inhibition of hypoxia-inducible factor-1 and the down-regulation of VEGF gene
      expression.
AB  - BACKGROUND: Previous reports indicate that Genistein, a naturally occurring
      isoflavonoid, exhibits strong antiangiogenic activity. The underlying mechanism
      of inhibition, however, remains unclear. Among the biologic effects of Genistein
      are the inhibition of tyrosine kinases and the inhibition of hypoxic activation
      of hypoxia-inducible factor-1 (HIF-1), one of the main regulators of VEGF gene
      expression. METHODS: Hypoxic cell culture was performed in a modular incubator
      chamber. Vascular endothelial growth factor (VEGF) protein secretion was measured
      using the enzyme-linked immunosorbent assay, binding of DNA by HIF-1 was measured
      using the electrophoretic mobility shift assay, and mRNA quantification was
      performed using Northern blot analysis. Pancreatic carcinoma was studied in an
      orthotopic murine model. Angiogenesis in vivo was quantified by staining
      xenograft tumors for endothelial cell markers. RESULTS: VEGF protein secretion
      was dose-dependently suppressed with increasing doses of Genistein. Furthermore,
      treatment of pancreatic carcinoma cells with Genistein led to impaired activation
      of HIF-1 under hypoxic culture conditions. Northern blot analysis indicated that
      VEGF mRNA expression decreased upon treatment with Genistein, both under normoxic
      and hypoxic culture conditions. In vivo, Genistein inhibited tumor growth for
      xenograft pancreatic carcinoma cells, whereas extensive hypoxia was observed in
      xenograft tumors and was not influenced by Genistein therapy. Similarly,
      decreased VEGF mRNA levels were observed in Genistein-treated Capan-1 xenograft
      tumors. CONCLUSIONS: The current study indicates that the previously reported
      antiangiogenic activity of Genistein probably is mediated by the inhibition of
      HIF-1, an important regulator of VEGF gene homeostasis, particularly under low
      oxygen conditions. Therefore, this bioactive compound may well be beneficial to
      patients with pancreatic carcinoma.

PMID- 14692042
TI  - Hypersensitivity and idiosyncratic reactions to oxaliplatin.

PMID- 14692043
TI  - Second neoplasms following megavoltage radiation for pediatric tumors.

PMID- 14692044
TI  - Re: Environmental tobacco smoke and risk of malignant lymphoma in pet cats.

PMID- 14692045
TI  - What's new on the dental scene? Browsing through the dental literature.

PMID- 14692046
TI  - An experimental method for in vivo analysis of biomechanical asymmetries of the
      periodontium.
AB  - For analysis of the initial tooth movement in vivo, an optical measuring
      apparatus with a resolution of 0.001 degree for rotation or 0.5 micron for
      translation respectively has been developed. Its design is described in detail.
      Because of its high sensitivity it is experimentally feasible to investigate the
      biomechanical properties of the periodontium under force application and to
      determine if it makes any difference whether a tooth is rotated mesially or
      distally out of its neutral position. For that purpose moments with defined time
      responses are buccally applied to premolars by means of a cardan shaft and the
      corresponding rotational angle-time characteristics are recorded. As expected,
      first measurements show sign symmetry for widely spaced teeth. In the case of
      pronounced anterior crowding, however, asymmetry seems to occur in such a manner
      that the force system has to overcome a threshold in order to rotate the tooth
      distally. Additionally, the periodontium may be subject to a sign-dependent
      rigidity. In all cases, the movement is limited to some degree.

PMID- 14692047
TI  - Interdisciplinary study of orthopedic and orthodontic findings in pre-school
      infants.
AB  - BACKGROUND AND AIM: The assessment of correlations between orthopedic and
      orthodontic data based on interdisciplinary studies is of scientific and
      practical interest in the differentiation of preventive diagnostic and
      therapeutic fields between orthodontics and orthopedics. In the published
      literature there are various studies analyzing the correlations between specific
      Angle classes and orthopedic parameters. Results of these studies indicate a
      potential correlation between scoliosis and Class II malocclusion as well as
      between weak body posture and Class II malocclusion. The aim of the present
      interdisciplinary study was to examine correlations between orthodontic and
      orthopedic findings in pre-school infants and to evaluate them with respect to
      preventive recommendations. PATIENTS AND METHOD: 59 pre-school infants (29 boys,
      30 girls) aged 3.5-6.8 years (mean: 5.0 years) were enrolled in this study. A
      standardized orthodontic and orthopedic examination protocol was used. RESULTS:
      The orthodontic examination showed Angle class distributions comparable with
      those in non-selected groups (Class I: 63%, Class II: 32%, Class III: 5%). The
      orthopedic examination revealed pathologic findings in 52% of the subjects, with
      statistically significant correlations between scoliosis and Class II
      malocclusion (p = 0.033) and between weak body posture and Class II malocclusion
      (p = 0.028). CONCLUSION: It can be concluded from the results that the
      orthodontic finding of Angle Class II in pre-school infants should induce
      prophylactic screening. The orthodontist could then not only initiate early
      orthodontic treatment to prevent incisor trauma in patients with extreme overjet,
      but could also take account of potential orthopedic malformations on a preventive
      interdisciplinary basis in pre-school infants with Class II malocclusions.

PMID- 14692048
TI  - Treatment begin and treatment effect in functional orthodontics with jumping-the
      bite appliances.
AB  - AIM: The aim of the present study was to investigate the effects of treatment
      begin in the early and in the late mixed dentition on treatment with jumping-the
      bite appliances. PATIENTS AND METHODS: Casts and lateral cephalograms of 69
      patients with Angle Class II, Division 1 malocclusions treated with jumping-the
      bite appliances were evaluated. RESULTS: A treatment begin in the early or late
      mixed dentition resulted in a highly significant reduction in overjet and
      overbite (p < 0.001), in [symbol: see text] SNA and in [symbol: see text] ANB (p
      < 0.001). An increase of [symbol: see text] SNB depended upon early (p < 0.001)
      and late (p < 0.01) treatment begin. In the vertical dimension, an early
      treatment start induced a slightly significant increase in [symbol: see text]
      NL/NSL and highly significant changes in the upper and lower incisors. With a
      late treatment start, these changes applied only to the lower incisors. The
      changes differed significantly only with respect to incisor inclination (upper
      arch p < 0.01, lower arch p < 0.05). The later the treatment start, the less
      significant were the dentoalveolar effects. CONCLUSION: At the end of the study
      period, a slightly significant intergroup difference was recorded for lower
      incisor inclination only.

PMID- 14692049
TI  - Invisalign--patient profiling. Analysis of a prospective survey.
AB  - AIM: The aim of the present prospective study was to produce a profile of those
      patients who are interested in treatment with the Invisalign system. PATIENTS AND
      METHODS: Personal data and clinical findings of 89 patients attending the
      Invisalign consulting hours offered by the Department of Orthodontics and
      Dentofacial Orthopedics, Charite Medical School were recorded. Personal data
      included gender, age, profession, motivation for treatment, accepted treatment
      duration, and initial source of information; clinical findings included anomalies
      of tooth position and jaw relationship as well as oral hygiene. RESULTS:
      Statistical analysis of the data revealed a characteristic profile: Mainly women
      between 20 and 29 years of age were interested in Invisalign treatment, chiefly
      for esthetic reasons, accepting a treatment time of 1.5 to 2.5 years. The
      majority of patients rejected treatment with visible appliances. 41% had been
      initially informed of this new treatment system by their dentist or an
      orthodontist, and the same percentage through different media. The standard of
      oral hygiene was only moderate or low in 54% of all subjects. Frontal crowding
      was diagnosed in 87%, and a Class II malocclusion in 49%. CONCLUSIONS: The demand
      for orthodontic treatment mainly among women is substantial, but many of these
      potential patients baulk at the esthetic impairment induced by a fixed labial
      appliance or the speech disturbances induced by a lingual appliance. In order to
      increase the acceptance of new treatment methods, the high demands placed by
      those concerned on esthetic and phonetic aspects should therefore be respected.
      With respect to oral hygiene, many patients are still in urgent need of
      professional instruction.

PMID- 14692050
TI  - Oral comfort, function and hygiene in patients with lingual brackets. A
      prospective longitudinal study.
AB  - BACKGROUND: Oral comfort, speech, mastication and swallowing, as well as oral
      hygiene were to be evaluated in a prospective longitudinal study before and after
      insertion of lingual brackets. PATIENTS AND METHOD: 22 patients (five male, 17
      female, mean age 34.7 years, SD 10.4) were enrolled in the study and filled in a
      standardized questionnaire directly before placement of lingual brackets (T0),
      within 24 hours thereafter (T1), and 3 months (+/- 1 week) later (T2). At both T1
      and T2, treatment was confined to the upper arch. RESULTS: In comparison with T0,
      significantly poorer results were recorded at T2 for the parameters "restriction
      of the tongue space", "lesions to the tongue", "tongue position", "subjective and
      semiobjective rating of articulation", "chewing", "biting" and "oral hygiene",
      although significant improvements, i.e. adaptations, had been recorded from T1 to
      T2 with the exception of the parameters "tongue space", "tongue position",
      "chewing", "biting" and "oral hygiene". At none of the registration timepoints
      was fluid intake impaired by the lingual brackets. CONCLUSION: The results of the
      present study suggest that detailed briefing on the extent and duration of
      potential impairments in oral comfort, functions and hygiene is advisable prior
      to the insertion of lingual brackets.

PMID- 14692051
TI  - A new bracket system for lingual orthodontic treatment. Part 2: First clinical
      experiences and further development.
AB  - BACKGROUND AND METHOD: Almost 20 months of practical application of a new lingual
      bracket system have revealed some clinically relevant advantages and
      disadvantages deriving from the original design. Numerous modifications in the
      design of the bracket bodies and bases have contributed towards further
      optimization of the appliance. The efficiency of the appliance is discussed,
      taking five treated cases as examples. RESULTS AND CONCLUSIONS: The initial
      demands for low bracket loss rates and simplified rebonding, controlled finishing
      and enhanced patient comfort have been largely met by the customized design and
      the flexibility in the manufacture of the new appliance. However, in the triad of
      orthodontist, patient and appliance that is of such great importance to any
      orthodontic therapy, any future ideal appliance will still offer no guarantee of
      a successful treatment outcome.

PMID- 14692052
TI  - Fractional excretion of magnesium of chronic renal failure patients in Lagos,
      Nigeria.
AB  - The objective of this study was to explore the usefulness of the fractional
      excretion of magnesium (FEMg2+) in Nigerian chronic renal failure patients (mild
      to moderate) in determining the severity of renal insufficiency. Plasma and
      twenty-four hour urine samples were analysed for magnesium and creatinine in
      thirty-five chronic renal failure patients and twenty-five healthy controls. The
      mean fractional excretion of magnesium (FEMg2+) was 15.3%(13.6) in the patients
      and 6.1%(2.3) in the controls and this correlated negatively with the creatinine
      clearance in both groups (r = -0.343, p < 0.05) in patients and (r = -0.665, p <
      0.001) in controls. There was a positive correlation between plasma creatinine
      and fractional excretion of magnesium in the patients (r = 0.463, p < 0.05) and
      controls (0.455, p < 0.05). FEMg2+ may therefore be a more sensitive indicator of
      renal insufficiency and may also be a better indicator of the progression of
      renal failure.

PMID- 14692053
TI  - CD4+ T-lymphocyte counts in patients with human immunodeficiency virus type 1
      (HIV-1) and healthy population in Jos, Nigeria.
AB  - This study was undertaken to establish local CD4+LC standards, which could be
      used as indicators of immune deficiency or monitor progress of HIV therapy,
      instead of relying on Caucasian standards, which may not exactly reflect Nigerian
      CD4+LC sub-populations. CD4+LC from 1232 Nigerian adults were studied. They
      included 852 apparently healthy individuals, 172 HIV-positive persons with no
      major AIDS defining illnesses (AIDSDIL) and 208 HIV infected individuals with
      AIDSDIL. The mean CD4+LC of healthy Nigerians (821 +/- 12) was more than two
      times higher than the mean CD4+LC of HIV-positive individuals without AIDSDIL
      (369 +/- 14) and almost five times higher than the mean of HIV-positive
      individuals with AIDSDIL (163 +/- 13) (p < 0.05). In addition, a CD4+LC of < 200
      cells/uL can be considered as an AIDS defining laboratory criterion in Nigerians
      as the 208 individuals with AIDSDIL had a mean CD4+LC of 163 cells/uL. This study
      therefore establishes a local standard range for CD4+LC in healthy and HIV
      infected Nigerians which can serve as reliable indices for HIV induced immune
      impairment and for monitoring effectiveness of HIV therapy.

PMID- 14692054
TI  - Surgical emergencies in a Nigerian university hospital.
AB  - An audit of surgical emergencies was carried out to monitor acute trauma care and
      determine areas needing clinical improvement. This is essential for the
      development of institutional and national health policies on trauma and non
      trauma diseases. All patients attending the surgical Accident and Emergency were
      studied prospectively from September 1999 to August 2000 to obtain their age, sex
      and diagnosis and to determine causes and injury-arrival time for trauma cases
      and the outcome of care for all cases. Out of 2,455 patients comprising 1,696
      males and 759 females (M:F = 2.2:1) age range two weeks to 95 years, trauma
      accounted for 1,679 (68.4%). The median age (and the mode) of presentation
      overall and in males was in the third decade. Females had a 'plateau' age of
      presentation for the first four decades before the gradual fall to zero.
      Superficial skin trauma (lacerations, abrasions and bruises) represents the
      commonest presentation (16.1%) followed by fractures (13.9%), acute abdominal
      conditions (7.6%), head injury, HI (5.5%), multiple injury (4.1%), urinary
      retention (3.3%), burns and scalds (3.3%) and others. Eight-one patients died,
      comprising 54 males and 27 females, out of which 64 were trauma related deaths.
      Most common causes of death were HI (35 patients, 43.2%) and septicaemia (13
      patients, 16.0%). Late presentation and poor finances contributed to the deaths
      in patients with septicaemia. Trauma is an important entity in our emergency
      practice. Prompt access to surgical care should reduce the morbidity and
      mortality from acute abdominal conditions and HI. The high incidence of urinary
      retention requires further analysis. Statistics of this nature can aid planning
      of care delivery and study of preventable deaths.

PMID- 14692055
TI  - Systemic hypertension in blacks: an overview of current concepts of pathogenesis
      and management.
AB  - Systemic hypertension is a leading risk factor for cardiovascular disease among
      Blacks. Essential hypertension in this population is dominantly related to salt
      sensitivity acting via various interactive mechanisms including volume changes,
      nitric oxide inactivation, angiotensin II and insulin resistance. Excess
      morbidity and mortality among Black hypertensives are related to twin problems of
      ignorance and poverty, late diagnosis, genetically determined racial biological
      factors and co-existing diabetes mellitus and obesity arising from "western"
      adopted affluent life-style. This paper reviews these peculiarities and their
      implications in the management of a Black Hypertensive.

PMID- 14692056
TI  - Multiple drug resistant strains of Shigella isolated in Jos, central Nigeria.
AB  - The objective of this study is to highlight the alarming rise in antimicrobial
      resistance among Shigella species in Jos, Plateau State. Stool samples of eight
      hundred and ten patients who presented at the Jos University Teaching Hospital
      with diarrhoea/dysentery were analysed using standard bacteriological techniques.
      The antimicrobial susceptibility of the isolates were determined. 25 Shigella
      species were isolated representing 3.1% isolation rate. The male to female ratio
      is 1.3:1, children aged 0-10 years constituted 16(64%) of the cases. Shigella
      flexneri (48%) was the most common sero-group. This was followed by S. boydii
      (24%), then S. sonnei (20%), and S. dysenteriae (8%). Most strains of shigella
      species were resistant to Ampicillin (96.0%). Chloramphenicol (96.0%),
      Cotrimoxazole (88%), Nalidixic acid (84%) and Tetracycline (75%). All strains
      were found to be sensitive to Ciprofloxacin. The drugs of choice in the treatment
      of Shigella infection in this environment should be Ciprofloxacin and Ofloxacin.
      Gentamicin was the third drug of choice its use is limited since the infection is
      not systemic. To avoid continuous abuse of antibiotics in our country there
      should be an effective legislation by the government to control the
      indiscriminate purchase of antibiotics.

PMID- 14692057
TI  - A cost comparison of traditional and orthodox mental health care.
AB  - This study examines whether cost is a factor in determining the choice of therapy
      in patients with mental illness. The focus therefore is to compare the cost of
      therapy (and not scientific basis or efficacy of treatment), in the short term,
      of traditional with orthodox mental health care. Sixty patients comprising 23 and
      28 patients receiving therapies at orthodox and traditional psychiatric
      facilities respectively were interviewed. Information was obtained in the areas
      of sociodemographic data, duration of illness before presentation, duration of
      therapy, costs of consultation, medication, accommodation and feeding among
      others. It was found that traditional mental health care, in the short run, was
      three times more expensive than orthodox mental health care. Future health
      campaign programs should emphasize the fact that traditional mental health care
      is not just less effective, but costlier than orthodox mental health care. This
      might further discourage people from patronizing traditional mental health
      practitioners.

PMID- 14692058
TI  - Negative pressure pulmonary oedema following tracheal tube obstruction in a
      paediatric patient: a preventable anaesthesia related morbidity.
AB  - The purpose of this study is to describe negative pressure pulmonary oedema due
      to undetected tracheal tube obstruction in a paediatric patient. A healthy 6 week
      old scheduled for release of tongue-tie under general anaesthesia was noticed to
      be diagnosed at the preparation of the surgical site. The patient was quickly
      assessed, and ventilation with 100% oxygen was commenced. The heart sounds were
      still present. Two minutes later, pink frothy secretion was noticed in the lumen
      of the tracheal tube. Assisted manual ventilation was continued for about 3 hours
      in the intensive care unit (ICU). Clinical examination after 8 hours of oxygen
      therapy indicated stable vital signs and was discharged to the ward. Undetected
      tracheal obstruction due to unsupervised patient positioning may result in
      negative pressure pulmonary oedema in a paediatric patient. Improved
      communication between the surgical and the anaesthetic teams may prevent this
      morbidity.

PMID- 14692059
TI  - Histopathologic diagnoses of lymphadenopathy in children in Jos, Nigeria.
AB  - Histopatholgical findings in 242 lymph node biopsies received in Jos University
      Teaching Hospital over a 10-year period (1988-1997) were reviewed. Tuberculosis
      is the most predominant lesion (33.05%), followed closely by the non-Hodgkin's
      lymphoma (31.4%). Burkitt's lymphoma accounting for one-quarter of all the cases
      of non-Hodgkin's lymphoma had a peak age range of 8-10 years. Hodgkin's lymphoma,
      chronic non-specific lymphadenitis, sinus histiocytosis, reactive hyperplasia,
      metastatic carcinoma, dermatopathic lymphadenitis, Kaposis sarcoma and
      sarcoidosis accounted for 2.9%, 14.46%, 9.9%, 4.96%, 1.7%, 0.4%, 0.8% and 0.4%
      respectively. The cervical region was the commonest site affected (54.1%),
      followed by mesenteric (22.3%), axillary (13.2%) and inguinal (10.3%). BCG
      immunization was carried out only on 121(50%) of cases, out of which 60 had
      tuberculosis and 54(22.3%) received no BCG immunization, while 67(27.7%) had no
      records of BCG immunization. Only 5(2%) had HIV screening done, out of which one
      was positive.

PMID- 14692060
TI  - Anthropometric measurements in the detection of low birth weight infants in
      Lagos.
AB  - The present study was undertaken to determine the anthropometric risk indicators
      in the detection of infants with low birth weight. A total of 788 consecutive,
      singleton, live born infants had anthropometric measurements determined within 24
      hours of life using standard methods. There were 389 (49.37%) males and 399
      (50.63%) females; 136 (17.56%) of the infants were of low birth weight (LBW).
      Birthweight was significantly correlated with occipitofrontal circumference (OFC;
      r = 0.66), length (r = 0.86), mid-arm circumference (MAC; r = 0.88) and maximum
      thigh circumference (MTC; r = 0.95) (p < 0.001). Furthermore, OFC of 33.6 cm and
      32.3 cm, length of 47.7 cm and 45.5 cm, MAC of 9.6 cm and 9.1 cm, and MTC values
      of 15.5 cm and 14.9 cm were the corresponding cut-off values with the best
      combination of sensitivity, specificity and predictive values (p < 0.001) for
      identifying infants with birth weights of < 2500 g and < 2000 g respectively. The
      use of these risk indicators would help to identify newborns for close
      supervision and care, as well as prevent mortality and postnatal developmental
      retardation.

PMID- 14692061
TI  - Impact of maximal cervical dilatation at primary caesarean delivery on mode of
      delivery in the following pregnancy.
AB  - The maximum cervical dilatation achieved by parturients who went through labour
      prior to their primary caesarean births were related to the mode of delivery in
      the subsequent birth to ascertain if there is a link between the two. The success
      rates of vaginal births after primary Caesarean sections (VBAC) for arrest and
      non-arrest disorders were also compared using information derived from the birth
      records of the hospital. The success rate for VBAC was significantly high in
      subjects whose primary caesarean sections were for non-arrest disorders compared
      to those who had arrest disorders (73.3% versus 55.6%; x2 = 5.25, p = 0.02). The
      maximum cervical dilatation reached before primary caesarean section did not
      significantly affect the success rate of VBAC in the subsequent delivery (x2
      [trend] = 0.78, p = 0.68). Patients who had primary caesarean section for arrest
      disorder require full evaluation before being allowed to attempt vaginal birth in
      a subsequent pregnancy but the maximum cervical dilatation reached before primary
      caesarean section need not be factored into a decision for VBAC.

PMID- 14692062
TI  - Maternal attitudes and values to youth sexuality-related activities in Delta
      State, Nigeria.
AB  - This descriptive study assessed maternal attitudes to youth-related activities in
      Delta State. Using an adapted questionnaire, 300 women with adolescent children
      were chosen through a multistage sampling technique and relevant data obtained
      regarding their socio-economic status, perceptions and values as well as their
      knowledge of basic reproductive health concerns. Most of the women interviewed
      (95%), believed it was very important that young people completed secondary
      education and another 72% said they would normally set rules in their homes
      regarding what young people should read or watch. Sixty-seven percent of those
      studied, discussed sexuality issues regularly with their adolescent children,
      though only 46.4% of them were comfortable discussing these issue and about 50%
      admitted having enough information in such discussions. Another 76% of the women
      would approve of their children receiving reproductive health information and
      service including contraceptive condoms. The mothers studied believed that guided
      reproductive health information and services should be routinely provided for
      young people. The findings strongly suggest that the mothers who are important
      stakeholders in Adolescent Health would most likely be supportive of youth
      programmes. Most of the findings differ from those of other studies, and a
      qualitative study would be carried out to identify the reasons for these
      interesting findings.

PMID- 14692063
TI  - Psychopathology among senior secondary school students in Ilesa, south western
      Nigeria.
AB  - The prevalence rate of psychopathology and the relationship between
      psychopathology and some socio-demographic variables and consolidated current
      drug use were studied in 600 randomly selected senior secondary school students
      in Ilesa, south-western Nigeria. The 30-item version of the General Health
      Questionnaire and the WHO student drug use questionnaire were administered for
      the study. The findings revealed that the prevalence of psychopathology among the
      study population was 39.5%. There were significant positive associations between
      psychopathology and belonging to low socio-economic status, coming from a
      polygamous family and self-rated poor academic performance. The results also
      showed that although psychopathology was commoner amongst respondents who were
      engaged in current use of psychoactive substances than those who were not, the
      difference was not significant. The implications of these findings within the
      context of the limitations of the study and the importance of effective
      preventive and therapeutic student mental health services are discussed.

PMID- 14692064
TI  - Mental laws in Nigeria: the case of the State Versus I. A.
AB  - The article focuses on providing medico-legal education for psychiatrists in the
      area of mental laws in Nigeria. This was done through the presentation of a
      recently concluded case of The State Versus I.A in which the author appeared in
      court to give evidence. A summary of the procedure before trial, the briefs of
      the prosecution and the defence, and the judgement were given. Some relevant
      sections of the Penal Code were quoted. Finally, salient points in the trial were
      also discussed. It was concluded that a good understanding of the mental laws by
      psychiatrists and medical personnel would lead to better presentation of evidence
      in court. Furthermore, a conference of stakeholders in mental health is also
      advocated.

PMID- 14692065
TI  - Food hygiene practices of food vendors in secondary schools in Ilorin.
AB  - This descriptive study was carried out to determine food safety practices among
      food Vendors in secondary schools in Ilorin. Pre-tested questionnaire and
      observational checklist were administered to 185 respondents recruited using
      inclusion and exclusion criteria. One hundred and eighty-two (98.4%) of the
      subjects were females and only 6(3%) were teenagers. One hundred and two (56.8%)
      had no formal education while 72(39% had received training on food hygiene. Pre
      employment medical examination practice was high 141(76%) but periodic medical
      examination was low 30(16%). Sixty-one (33%) and seventy-two(39%) respondents
      prepared food well in advance and reheat food before sale respectively. Vendors
      who prepared food well in advance (over 4 hours) were found to practise food re
      heating more than those who prepared food within 4 hours before sale, and this is
      statistically significant. The major unhygienic practices observed among the food
      vendors were poor care of used utensils 100(54%), use of previously used water
      for washing and cleaning, lack of covering apron among the vendors 128(69%) and
      lack of wash hand basin for immediate cleaning 61(33%). Only 85(46%) of the
      respondents used soap and water to clean their utensils while the rest 100(54%)
      used unhygienic methods to clean their utensils. It was observed that respondents
      who used soap and water for cleaning, vended food at locations that were
      relatively closer to water source, compared to other vendors who used other
      methods to clean their utensils. This is also statistically significant. Unkempt
      fingernails, skin lesions and poor food protection from flies were some of the
      food contaminating risk factors observed in the study. The need exists for food
      vendors and other food handlers to be trained on basic principles of safe food
      handling.

PMID- 14692067
TI  - Culture as context for holistic nursing.

PMID- 14692066
TI  - Structured and unstructured abstracts in journal articles: a review.
AB  - Abstracts in journals are important paragraphs in review or original articles,
      which help one to decide if such articles are worth reading. The layout and the
      content of abstracts have undergone tremendous changes over the years from
      traditional, unstructured to structured, informative format. Many journal editors
      abroad are moving fast with time in the adoption of the innovation, allowing only
      articles with structured abstracts to appear in their journals. Journals in
      Africa especially in Nigeria are lagging behind in this respect. This review
      article examines the relative advantage of structured abstracts over unstructured
      abstracts as documented by various reports on the subject and makes a
      recommendation for structuring abstracts in articles appearing in Nigerian
      Journals.

PMID- 14692068
TI  - Las que curan at the heart of Hispanic culture.
AB  - Bilingual nurse-curanderas are an emerging group of health care providers who
      blend the profession of nursing with Hispanic folk healing, thus providing
      culturally competent care to one of the largest growing minority groups in the
      United States. Nurse-curanderas integrate curanderismo (Hispanic folk healing)
      with allopathic health care, evaluate safety and efficacy, and implement
      appropriate interventions. This balance reduces cultural conflict and improves
      outcomes by increasing patient compliance with the treatment regimen. A Spanish
      English glossary of terms used is included.

PMID- 14692069
TI  - Influential life contexts and environments for out-of-home pregnant adolescents.
AB  - This focused ethnography explored influential life experiences and environmental
      contexts associated with pregnancy among "out-of-home" pregnant adolescent women
      in Seattle (i.e., not living in stable settings or with parents). Methods adapted
      from feminist anthropology guided ethnographic interviewing and participant
      observation. Key informants (N = 8) included 5 White, 1 American Indian, and 2
      African American women 17-19 years, plus expectant fathers and street friends.
      Narrative and domain analysis focused on life events and current experiences that
      participants linked to their pregnancy decisions. Participants organized their
      narratives primarily around relationships: conflict-laden family relationships,
      violence and sexual abuse in childhood, mental health and substance abuse
      problems, and life-long patterns of housing instability. Economic challenges,
      disconnection to school, and spiritual change were important in their current
      circumstances. For most, out-of-home status preceded pregnancy, and during
      pregnancy, housing options improved slightly. For others, pregnancy occurred
      within a relationship that offered them relatively more stable housing
      arrangements.

PMID- 14692070
TI  - Woman to woman. Complementary therapy use in menopause.
AB  - Many women are turning to herbal, homeopathic, dietary, and other complementary
      therapies for relief of stressful aspects of menopause. Several questions related
      to complementary therapy use are not, however, well addressed in current research
      literature. Why do women seek out complementary therapies? Which therapies do
      they choose and why? What is the nature of their experiences using complementary
      therapies? In this qualitative study, 19 Caucasian women, who identified
      themselves as using or having used complementary therapies during menopause were
      interviewed in one of four focus groups. Findings revealed a wide variety of
      therapies, such as vitamin, mineral, and herbal preparations and lifestyle and
      behavioral initiatives, used to address distressing aspects of menopause. Also
      identified was lack of family and professional support for women who are seeking
      complements or alternatives to conventional treatment.

PMID- 14692071
TI  - Nurses and nutraceuticals. Knowledge and use.
AB  - Increasing use of herbal products by the American public should prompt nurses to
      routinely address herbal use during patient interactions. However, whether nurses
      possess the knowledge required to discuss risks and benefits of herbal use with
      patients is unknown. This study was undertaken to investigate registered nurses'
      knowledge about and use of five common herbal products: ginkgo, St. John's wort,
      ginseng, garlic, and echinacea. One hundred forty-nine (30%) of 500 randomly
      selected nurses responded to a mailed questionnaire addressing the frequency of
      use, purpose, side effects, and interactions of the above products. Most
      respondents had neither used nor suggested use of the products. Respondents were
      relatively unfamiliar with product characteristics, although somewhat more
      familiar with purpose than with side effects or interactions. No knowledge
      differences were identified according to practice area or number of years in
      practice, but differences were noted according to educational level and use of
      specific products.

PMID- 14692072
TI  - Humor. An antidote for terrorism.
AB  - It has been more than 2 years since the terrorist attacks of September 11, and
      the emotional fallout is still being felt. Nurses need to understand the crisis
      presented by terrorism and explore ways of dealing with it. The purpose of this
      article is to discuss humor as a means of facilitating coping with terrorism.
      Terrorism is a humanly caused disaster that threatens the physical, psychosocial,
      and spiritual aspects of one's personhood. The effects of humor strengthen these
      dimensions of self. In trying to deal with a terrorist event, people pass through
      several phases of emotional adjustment. Humor is a holistic, noninvasive strategy
      that may facilitate that adjustment and may be used effectively to heal both
      survivor-clients and disaster personnel who are working with them. Awareness of
      the phases of emotional adjustment, associated humor styles, and ways to
      incorporate therapeutic humor into crisis management approaches are essential for
      effectively using humor as an antidote for terrorism.

PMID- 14692073
TI  - Managing utilization of new diagnostic tests.
AB  - In appropriate utilization of laboratory testing has been estimated to range from
      10% to 50% of the volume encountered in hospital laboratories. Many strategies to
      control utilization of laboratory testing have been reported, including
      redesigning test requisitions, changing standing orders, the use of provider
      order entry, physician profiling, and educational initiatives. The major
      motivation to reduce utilization of unnecessary testing is financial, although
      other benefits also may be observed, such as reducing false-positive results
      stemming from testing patients in low prevalence populations, eliminating
      unnecessary follow-up procedures, avoiding iatrogenic anemia, and potentially
      lowering hospital length of stay resulting from the need to track down the
      significance of falsely abnormal tests. The majority of utilization control
      efforts have focused on reducing routine laboratory tests such as chemistry
      profiles and automated blood counts. In many hospitals novel diagnostic tests,
      especially in molecular genetics and oncology, are the major driver behind
      increasing laboratory costs. Traditional methods to control utilization of
      routine testing are usually ineffective in controlling testing of novel
      diagnostic methods. In most cases, test requests originate from a small group of
      physician specialists who typically are more knowledgeable in their area of
      expertise than is the clinical pathologist. For this reason, a different approach
      is generally required. It is particularly important to establish an institutional
      structure authorized to review and approve new laboratory tests. The clinical
      pathologist usually takes the lead in this effort because laboratory-based
      physicians are familiar with new tests being requested by physicians across a
      spectrum of medical specialties. To be successful, the laboratory physician must
      identify potential utilization issues, acquire and analyze data, function on
      interdepartmental teams, and develop strategies to satisfy the needs of
      clinicians while at the same time preventing introduction of inappropriate
      technologies into the laboratory. This article will give a perspective on
      approaches to laboratory test utilization and offer specific examples of
      initiatives we have undertaken in our institution. The examples will illustrate
      how the pathologist can use knowledge of medicine and the clinical laboratory in
      conjunction with organizational and team building skills. In the final analysis,
      the process is more of an art than a science.

PMID- 14692074
TI  - Effectively managing your reference laboratory relationship.
AB  - Clinical laboratories use reference laboratories for laboratory services that
      they, themselves, routinely are unable to provide, often for economic and/or
      competency-related reasons. Decisions on reference laboratory providers usually
      are based upon reputation, quality of service, depth of test menu, other value
      added services, testing frequency and turnaround time, price, client services
      support, information technology support, and logistics. The referring laboratory
      also is faced with the challenge of how to manage physician ordering patterns and
      their requests for esoteric testing. This is particularly important and
      problematic in cases of questionable medical necessity, high cost, or both. This
      article attempts to address this dilemma and how best to manage the utilization
      of expensive esoteric tests, particularly in the face of little or no
      reimbursement for these services by payers and health plans.

PMID- 14692075
TI  - Make versus buy: a financial perspective.
AB  - Clinical laboratories are often faced with the decision to either perform a
      service in-house using their own assets or outsource the service to another
      vendor. This decision affects many aspects of the laboratory's business, from the
      macroeconomic perspective of outsourcing the laboratory service to a laboratory
      vendor, to the microeconomics of determining whether to refer a test out to their
      reference laboratory or perform the test in-house. The basis for decision making
      includes many variables, but a detailed financial analysis is usually the basis
      for the decision, especially when the decision only affects the laboratory and
      not the rest of the institution. Other factors often come into play, and
      depending on the magnitude, the "make versus buy" decision could be based more on
      strategic or political factors than economics. Even when noneconomic factors are
      involved, an effort usually is made to quantify those factors so that the make
      versus buy decision is reduced to financial terms. The previous article in this
      issue, "Effectively Managing Your Reference Laboratory Relationship" by Ronald L.
      Weiss, M.D., focused on the "buy" decision relating to managing the reference
      laboratory relationship. Although that article took a more clinical perspective
      through the eyes of the reference laboratory, this article looks at the make
      versus buy decision from a financial perspective through the eyes of the buying
      party.

PMID- 14692076
TI  - The role of the independent clinical laboratory in new assay development and
      commercialization.
AB  - Most would agree that these are exciting times in the field of laboratory
      medicine. As the body of scientific knowledge expands and research activities,
      such as those catalyzed by the sequencing of the human genome, bring us closer to
      the promise of personalized medicine, the clinical laboratory industry will have
      increasing opportunities to partner with owners of intellectual property to
      develop and commercialize new diagnostic tests. The large, independent clinical
      laboratories are particularly well positioned to commercialize important new
      tests, with their broad market penetration, infrastructure, and the scale to run
      esoteric tests cost-effectively.

PMID- 14692077
TI  - Targeted therapy for cancer: the HER-2/neu and Herceptin story.
AB  - The HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor with
      extensive homology to the epidermal growth factor receptor. In this article, the
      association of HER-2/neu gene and protein abnormalities with prognosis and
      response to therapy with Herceptin and other therapies in breast cancer is
      presented. By considering a series of 80 published studies encompassing more than
      25,000 patients, the relative advantages and disadvantages of Southern blotting,
      polymerase chain reaction amplification, and fluorescence in situ hybridization
      assays designed to detect HER-2/neu gene amplification are compared with HER
      2/neu protein overexpression assays performed by immunohistochemical techniques
      applied to frozen and paraffin-embedded tissues and enzyme immunoassays performed
      on tumor cytosols. The significance of HER-2/neu overexpression in ductal
      carcinoma in situ and the HER-2/neu status in uncommon female breast conditions
      and male breast cancer also are considered. The role of HER-2/neu testing for the
      prediction of response to Herceptin therapy in breast cancer is presented as well
      as its potential impact on responses to standard and newer hormonal therapies,
      cytotoxic chemotherapy, and radiation. The review also will evaluate the status
      of serum-based testing for circulating HER-2/neu receptor protein and its ability
      to predict disease outcome and therapy response.

PMID- 14692078
TI  - HPV: from the cervical smear to the research bench to the court room.
AB  - The human papillomavirus (HPV) is one of the most common sexually transmitted
      viruses in our culture, yet there is a high level of misunderstanding about its
      detection and usual biological course. The Pap smear, one of the most common
      specimens in a cytology laboratory, is one of the easiest ways to detect HPV
      infection. However, this is a screening test and comes with many diagnostic and
      laboratory management problems. The Pap smear accounts for one of the highest
      themes for malpractice suits, putting a great need on laboratories to maintain
      superb quality assurance measures. Much effort is underway toward better
      prevention and treatment of this virus. Decades from now, this now almost
      ubiquitous virus may prove to be a rare infection.

PMID- 14692079
TI  - Genetic testing coverage and reimbursement: a provider's dilemma.
AB  - The rapid growth of new molecular genetic tests stimulated by the diagnostic
      potential of DNA/RNA analyses has resulted in the capability of molecular genetic
      assay technology outpacing the American Medical Association Current Procedural
      Terminology (CPT) codes and Medicare reimbursement. The AMA CPT Editorial Panel
      is poised to change the way we report genetic testing, and this change may have
      the potential to stimulate a governmental review of how Medicare is paying for
      diagnostic genetic testing. Genetic assays are costly, and those in laboratory
      management need to be aware of potential changes that may influence the ability
      of their laboratory to provide access to genetic testing services for their
      physician clientele. The commercialization of genetic testing has resulted in a
      proliferation of commercial laboratories and university medical center
      laboratories, CLIA-certified to perform high complexity testing, offering some
      level of genetic testing. The genetic tests are offered as home brew (in-house
      developed) assays, most of which are using analyte-specific reagents. Because
      these are home brew assays, there is no standardization in how the industry tests
      for specific mutations. As these genetic assays are billed using the generic
      molecular diagnostic codes, 83890 through 83912, from the Pathology and
      Laboratory Chemistry subsection of the CPT, payers are not able to identify the
      specific mutations being tested and make payment determinations based on the
      mutations as they relate to the diagnosis code. This article discusses the
      history of molecular diagnostic coding and related reimbursement, current
      coverage issues, and the genetic coding proposal under consideration by the AMA
      CPT Editorial Panel.

PMID- 14692080
TI  - The link between providers and patients: how laboratories can ensure quality
      results with genetic testing.
AB  - Advances in genetic testing technology can provide important opportunities for
      health improvement. Simultaneously, they entail complexity in laboratory analysis
      and interpretation. The nature of genetic testing may engender implications
      distinct from other diagnostic tests. In this article, we summarize these
      implications, including the role of informed consent; quality assurance in
      diagnostic testing services; interpretation of the test results; patient support;
      appropriate disclosure; and regulations relevant for laboratories involved with
      genetic tests. Research and clinical laboratories need to stay abreast of these
      advancing technologies and their implications for health-care patients and
      providers. Collaboration between testing personnel, geneticists, and other health
      care providers is necessary to ensure that patients receive the full benefits
      from testing, including a clear understanding of their genetic test information.

PMID- 14692081
TI  - Consumer direct access to clinical laboratory testing: what are the critical
      issues?
AB  - Americans are demanding, independent people. In most aspects of our lives, we are
      used to walking into a store or other place of business with the expectation that
      the personnel working for the business will make every effort to satisfy our
      requests quickly and without the need for a third party to intervene or approve
      the transaction. Hence, the popularity of convenience stores, do-it-yourself
      stores and kits, and e-commerce. The delivery of health-care services, however,
      generally does not conform to this model. Before most diagnostic tests or
      treatments are ordered, patients usually consult a physician. In many cases,
      prior to tests or treatments being performed, additional consultations are
      required with insurance plans. But the winds of change, they are a-blowing. More
      and more, people demand an active role in managing their health care. One
      emerging trend is direct patient access to clinical laboratory testing (1).

PMID- 14692082
TI  - Career development strategies. The learning department, Part I.

PMID- 14692083
TI  - Case studies in ethics. DAT and DTC advertising.

PMID- 14692084
TI  - Dollar$ & Sen$e. Common cent$ 15: enough is enough.

PMID- 14692085
TI  - Laboratory design. Learning a new language.

PMID- 14692086
TI  - As we see it. The post-genomic revolution.

PMID- 14692087
TI  - Inside the physician office laboratory. Continuing education: what drives your CE
      program?

PMID- 14692088
TI  - [Study of accidents in the Koprivnica area].
AB  - The aim of this paper is to present injury incidence, risky population groups,
      circumstances and activities before the accident and injury mechanism in
      Koprivnica district (715 km2, 61,052 inhabitants). Data were taken from the
      Register which includes all population who were injured in this area. Register
      was located in surgical unit, general hospital in Koprivnica. During study period
      Jan 1, 1998-Jun 30, 2000 there were 4833 injured persons registered. Males had
      significantly higher injury incidence (40.9/1000) than females (23.8/1000) (P <
      0.01). The highest incidence among male population was in the age 15-24 yrs.
      (66.3/1000) and among females in the age 0-14 yrs. (35.6/1000). The most risky
      time for accidents was on Saturday (18.7%) and at 12-18 p.m. (53.2%). The highest
      road traffic accident mortality was in older age (65 and over) (110.3/100,000)
      and the highest injury incidence was in younger age (15-24 yrs.)
      (3200.6/100,000). Regarding other accidents, the most risky place was around the
      house, in garden (26.6%). The most frequent injury mechanism for both genders is
      slipping (16.5%); in men follow cuts (12.8%) and being hit from the moving object
      (12.3%) and in women follow fall on (from) stairs (12.5%) and cuts (10.7%). The
      most frequent activity before an accident appears is unpaid work with tools,
      machines and other (15.7%). More detailed investigation on the local level makes
      possible suggesting more efficient injury prevention programs.

PMID- 14692089
TI  - [Minor physical anomalies in children with hearing impairment].
AB  - The prevalence of minor physical anomalies was studied on a sample of 116
      children with idiopathic hearing impairment (66 boys and 50 girls). The control
      group consisted of 246 children with normal hearing (123 boys and 123 girls) aged
      from 8 to 12 years. The number of minor anomalies found per child (W1) was
      compared and the sum of the weighted scores according to Waldrop (W2) in children
      with normal hearing (CNH) and children with impaired hearing (CIH). A higher
      minor physical anomalies score was determined per child in the CIH group. In the
      CNH group there were 4 or more (33.6%) with multiple anomalies, while in the CNH
      group there were only 7.7% with four or more anomalies. A high score (W2) of five
      or more anomalies was determined in 18.9% of children in the CIH group and not
      one subject in the control group. Differences between the CIH and CNH groups for
      the mean score W1 and W2 were highly significant. The mean score W1 for CIH was
      2.90 and for CNH 1.70. The mean score W2 for CIH was 2.93 and for CNH 1.46.
      According to the obtained results etiological factors probably had a parallel
      effect in CIH during early development, which lead to physical and hearing
      impairment. The high incidence found of multiple minor anomalies in CIH suggests
      a significant role of genetic factors in the aetiology of the basic disorder in
      the group of analysed children.

PMID- 14692090
TI  - [Treatment of chronic myeloid leukemia with imatinib in the accelerated stage of
      the disease].
AB  - Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML), in advanced
      stage of disease, is resistant to standard chemotherapy. Imatinib was found to be
      effective in these patients. This paper shows our preliminary results. Imatinib
      mesylate was given to 15 patients during a 9-month period. Nine of them were in
      accelerated phase and 6 in blastic crisis of Ph+ CML. Patients were evaluated for
      hematologic and cytogenetic responses. Imatinib mesylate induced complete
      haematologic response in 12 patients (80% and cytogenetic response in 8 patients
      (53%). Six patients (40%) had a major cytogenetic response. After a 9-month
      follow up Ph+ CML progressed in 9 patients (60%) and 4 of them died. The most
      frequent adverse effects were edema, nausea, neutropenia and thrombocytopenia.
      Imatinib mesylate has a substantial, but short term activity in the accelerated
      phase and blastic crisis of the Ph+ CML.

PMID- 14692091
TI  - [Cytodiagnosis in irradiated breast cells--its value and pitfalls].
AB  - Morphologic changes in glandular epithelium of the breast after quadrantectomy of
      the breast carcinoma and radiotherapy are described. The aim of the study was to
      establish the possibilities of cytologic assessment of morphological changes in
      palpable lesions in the residual breast tissue. Fine needle aspirates of 50
      patients after surgery and radiotherapy of the breast carcinoma were analyzed.
      Biopsy and pathohistologic verification were performed in 12 patients. Carcinoma
      was cytologically found and confirmed pathohistologically in two cases.
      Recurrence was pathohistologically confirmed in 3/10 (33.3%) cytologically
      suspect aspirates, while in the remaining 7/10 (66.7%) suspect findings benign
      changes were established (2 mild ductal proliferations, 2 florid ductal
      proliferations, 3 cases of adenosis). The patients were followed-up clinically
      and cytomorphologically. No relapse was noted in the follow up period. Although
      its role is limited, fine needle aspiration cytology is useful in the assessment
      and follow-up of palpable changes after irradiation. A cytologist should be
      informed on whether and when a patient underwent irradiation. The finding of the
      changed cell after the period without changes points to the relapse of the
      disease.

PMID- 14692092
TI  - [Occurrence of chronic B-cell lymphocytic leukemia in Hodgkin's disease: case
      report].
AB  - We present a case of a female patient (79 years) with pathohistologic diagnosis
      of Hodgkin's lymphoma (HL) (stage IIIB, histologic type MC) for which she was
      treated with chemotherapy according to LVPP protocol (6 cycles) with good
      therapeutic response. Unexpectedly, 18 months after HL diagnosis leukocytosis
      occurred (19.4 x 10(9)/L) with 65% of lymphocytes with lymphoplasmocytic
      differentiation. Immunophenotype of these cells is typical for B-chronic
      lymphocytic leukemia (B-CLL) (CD5/CD19+, CD23-, CD38 +/-; with weak expression of
      monoclonal light chains lambda). Molecular analysis confirmed clonal
      immunoglobulin heavy chain gene (IgH) rearrangement of peripheral blood
      lymphocytes. The diagnosis of B-CLL imposed the question of the connection
      between two neoplasms of lymphocytic origin. Molecular analysis of lymph node
      biopsy taken at the time of lymphoma diagnosis revealed clonal population of B
      lymphocytes. That test undeniably proved coexistence of both diseases from the
      beginning. The latest PCR analysis of archive peripheral blood smears confirmed B
      lymphocyte clonality without diagnostic criteria for lymphoproliferative disease
      of CLL type. This finding etiologically excludes secondary leukemia. The
      possibility of untypical presentation of CLL in transformation to Richter's
      syndrome with morphologic characteristics of HL from the beginning stays
      unconfirmed. The hypothetical question that remains unanswered is: "Was it one
      disease in different clinical forms?"

PMID- 14692093
TI  - [Kt/V as a measure of hemodialysis adequacy].
AB  - Dialysis efficacy and single hemodialysis urea removal is expressed as Kt/V value
      (normalized treatment ratio). All formulae for delivered Kt/V calculation are
      based on Gotch-Sargent's urea kinetic model solution for single dialysis. Error
      in calculation Kt/V results from falsely low postdialysis blood urea
      concentration in respect to real body urea concentration. Reasons for the low
      blood urea postdialysis value are recirculation (in blood access and
      cardiopulmonary) and postdialysis urea rebound. The Kt/V value is important for
      the outcome of the patients undergoing chronic hemodialysis therapy. There is a
      strong correlation between higher Kt/V value and lower mortality. This value must
      be precisely estimated. Novel methods for urea concentration measurement from
      spent dialysate with on-line monitors provide precise Kt/V calculation. These
      methods circumvent mistakes of postdialysis blood urea concentration estimation.

PMID- 14692094
TI  - [Endoscopic ultrasonography and diagnostic algorithms in diseases of the
      gastrointestinal tract].
AB  - This article reviews the recent literature on the role of endoscopic
      ultrasonography (EUS) as diagnostic and therapeutic tool, defines its place in
      the algorithm of diagnostic procedures and informs how to treat some patients
      evaluated by EUS. Endoscopic ultrasonography utilizes the technology of endoscopy
      to introduce high frequency ultrasound probes in the upper or lower part of
      gastrointestinal tract to visualize gastrointestinal wall and adjacent
      structures. This method has come out as an important modality for the diagnosis
      and staging of benign and malignant lesions of the gut wall and surrounding
      structures of the mediastinum, abdomen and pelvis. It is also used as a
      diagnostic tool for the evaluation of submucosal masses of the upper
      gastrointestinal tract and the rectosigmoid, for locating pancreatic endocrine
      tumors, and for the assessment of vascular disease. Interventional applications,
      such as EUS-guided fine-needle aspiration (EUS-FNA) for obtaining tissue/fluid
      samples, for pseudocyst drainage, and also for delivery of local therapy will
      likely enhance the clinical utility and cost-effectiveness of this imaging
      modality. The widest application of EUS is, however, in the diagnosis and staging
      of esophageal, gastric, rectal, and pancreaticobiliary carcinoma. EUS has been
      shown to change the approach to clinical management in a significant proportion
      of patients to a less costly, risky, or invasive strategy.

PMID- 14692095
TI  - [Recommendations for care of patients with cerebral accident. Part One:
      Organization of care for patients with cerebral accidents, treatment of cerebral
      accident and neurorehabilitation].
AB  - Stroke is the leading cause of disability in modern society. In developed
      countries stroke is the second or the third cause of death, and in Croatia it is
      the leading cause of death. Therefore, stroke is not only a great medical, but
      also economic burden. Figures show that the incidence of stroke in transitional
      countries is increasing, so the epidemic of stroke could be expected in the
      forthcoming years. The Croatian Society for Neurovascular Disorders of the
      Croatian Medical Association and the Croatian Stroke Society wrote the
      recommendations for stroke management. The first part presents the
      recommendations for organization of stroke care, stroke treatment and
      neurorehabilitation, and the second part will present the recommendations for
      prevention of stroke.

PMID- 14692096
TI  - [The Journal of Slavonian Physicians (Glasnik druztva Slavonskih Liecnika), the
      journal of the medical society in Croatia 1877-1878].
AB  - If we discuss chronological appearance of medical journals as official gazettes
      of medical associations in this part of the world and Europe, then Glasnik
      druztva slavonskih liecnika (Glasnik DSL) is the first and the oldest medical
      journal of this kind in Croatia, whose first number is dated January 1, 1877, and
      the last December 1, 1878. It is the gazette of the Slavonian Medical Association
      in Osiek (DSL in Osiek), a professional medical association founded in 1874,
      which today marks its activity as the Croatian Medical Association--Osijek Branch
      (HLZ). Our goal was to investigate the key determinants of its appearance in the
      context of the role and contribution of Slavonian physicians in the promotion and
      development of Croatian medical literature, particularly medical periodicals in
      the 19th century. The conclusions we reached are based on the knowledge acquired
      during previous investigations on the history of medical associations and
      development of professional medical periodicals in Croatia and Slavonia in the
      19th century, and on the historical material and preserved documentation of DSL
      in Osiek, HLZ in Zagreb, and Glasnik DSL from the beginning of 1874 through 1878.
      Basic determinants of the appearance and relatively short duration of the monthly
      periodical Glasnik DSL are highlighted, with the emphasis on: 1) events preceding
      its publication, including initiatives of physicians in Slavonia for the
      development of Croatian medical terminology, professional medical publications,
      particularly medical journals from the middle of the 19th century through 1876;
      2) circumstances accompanying the publication of the journal Glasnik DSL in the
      period from January 1, 1877 through 1878; 3) events contributing to making
      decision on discontinuation of its publishing. The results are presented in
      several separate chapters which offer new scientific knowledge about the history
      of the medical Journal Glasnik DSL, and about the role of Slavonian physicians
      and DSL in Osiek in the promotion of Croatian medical terminology and the
      development of professional medical literature from the middle of the 19th
      century through 1878. In Glasnik DSL we today recognize our first medical
      periodical as the oldest scientific and professional gazette of the medical
      association; the unique source and material for studying the history of Croatian
      medical journals; history of medical associations; health-related circumstances,
      conditions of work and striving of physician, and professional and scientific
      scopes in Croatia in the 19th century. Each number is by itself a value and a
      bibilographic rarity, all numbers together represent a unique monument to
      Croatian medical heritage, whose availability for the new generations is
      facilitated by publishing the reprint issue in 1999.

PMID- 14692097
TI  - National service.

PMID- 14692098
TI  - Blast from the past.

PMID- 14692099
TI  - Wait for it!

PMID- 14692100
TI  - Drop of the hard stuff.

PMID- 14692101
TI  - The HSJ interview: Lord Warner. Ping-pong wizard. Interview by Helen Mooney.

PMID- 14692102
TI  - Clinical management where medicine meets management. Get out, stay out.
AB  - The project uses techniques common in substance misuse treatment to help prevent
      mental illness relapses. Cognitive behavioural training helps patients and carers
      better manage their care. Audit shows a reduction in admissions and length of
      stay.

PMID- 14692103
TI  - Regeneration. The generation aim.
AB  - In the late 1990s, Manchester had 27 out of 33 of the UK's top 10 per cent most
      deprived wards. The Wythenshawe Forum development aims to transform primary care
      and leisure facilities. Funding comes from a range of local, central and European
      sources.

PMID- 14692104
TI  - Finance. There shall come a great profit.

PMID- 14692106
TI  - [Reality and expectations of cardiology].

PMID- 14692105
TI  - HSJ people. Ifs and cuts.

PMID- 14692107
TI  - [Cellular technologies in cardiology].

PMID- 14692108
TI  - [The cardiovascular and endovascular surgery: modern technologies and
      achievements in prevention and treatment of adults and children].

PMID- 14692109
TI  - [Phlebology--the most important issue in angiology and vascular surgery].

PMID- 14692110
TI  - [Development and application of new biomedical technologies in the diagnosis and
      treatment of cardiovascular diseases].

PMID- 14692111
TI  - [Coronary revascularization: current surgical standards and alternatives].

PMID- 14692112
TI  - [Development and implementation of new technologies into the cardiological and
      cardiosurgical practice].

PMID- 14692113
TI  - [Potentialities of vascular surgery in the prevention of ischemic cerebral
      stroke].

PMID- 14692114
TI  - [Current genetic technologies in the diagnosis and treatment of cardiovascular
      diseases].

PMID- 14692115
TI  - [Cerebral stroke: problems and solutions].

PMID- 14692116
TI  - [Stroke as mirrored by medicine and society].

PMID- 14692117
TI  - [Cardio-renal ratio and the risk of cardiovascular diseases].

PMID- 14692118
TI  - [Diagnosis, prognostication, and prevention of sudden cardiac death in patients
      with cardiological diseases].

PMID- 14692119
TI  - [Impaired lipid metabolism: approaches to prevention and therapy].

PMID- 14692120
TI  - [Atrial fibrillation: electrophysiological mechanisms and new approaches to
      interventional treatment].

PMID- 14692121
TI  - [Acute rheumatic fever and rheumatic heart diseases: present and future].

PMID- 14692122
TI  - [Mechanisms of the damaging action of cerebral ischemia and neuroprotection].

PMID- 14692123
TI  - [P. G. Sergiev (on the occasion of his 110-th birthday anniversary)].

PMID- 14692124
TI  - [Coagulation status in patients with deep venous thrombosis of the lower
      extremities].
AB  - PURPOSE: Venous thromboembolism is a relevant social and health care problem for
      its high incidence, pulmonary embolism-related mortality and long-term sequelae
      which may be disabling (post-thrombotic syndrome and ulceration). PROCEDURES: The
      aim of our work was to establish the presence of coagulation disorders
      (hypercoagulable states) in the patients with deep vein thrombosis (DVT) of the
      leg. Prospectively we have analyzed a group of 30 patients with
      echosonographicaly verified DVT of the leg who were admitted to the department of
      vascular surgery from August 1st 2000 to July 31st 2001. The following parameters
      were monitored: prothrombin time (PT), partial thromboplastin time (PTT),
      fibrinogen (Fib), alpha 2 anti-plasmin (A-2 AP), D-dimer (DD), antithrombin III
      (AT III) and factor VII. FINDINGS: Activation of the coagulation process was
      registered. The values of monitored coagulation parameters are shown in table 1.
      Plasma levels of monitored parameters in the patients with DVT of the leg were
      significantly higher than in the control subjects. CONCLUSION: In patients with a
      DVT a hypercoagulable state is common finding. Some parameters of coagulation
      activity such as D-dimer might be of great interest in the diagnostic strategy of
      DVT.

PMID- 14692125
TI  - ["Flash" pulmonary edema as a clinical manifestation of renovascular
      hypertension].
AB  - One of the clinical manifestations of renovascular hypertension (RVH) may be a
      recurrent pulmonary oedema both in the absence or in the presence of systolic
      left ventricular dysfunction. This type of pulmonary oedema characterized as
      "flash" pulmonary oedema is ascribed to elevated angiotensin II concentrations
      with consequent hypertension as well as to volume overload resulting from
      decreased pressor natriuresis when there are significant stenoses of both or one
      renal arteries. The investigation included 30 patients with RVH treated by
      percutaneous transluminal angioplasty of the stenosed renal artery (PTRA) and/or
      stent implantation (PTR-ST) and 30 patients with surgical resection of the
      abdominal aortic aneurysm (AAA). The first group was divided in two subgroups
      according to the etiology of renal artery stenosis (RAS). In the subgroup with
      fibromuscular dysplasia (FMD) the mean age was 37.5 years, in the subgroup with
      atherosclerotic renal artery stenosis (ARAS) 54.8 years and in the group with
      operated AAA 68.6 years. There were more females than males only in the FMD
      subgroup (10:3). Two patients of the first group experienced pulmonary oedema,
      both in the subgroup with atherosclerotic renal artery stenosis associated with
      atherosclerosis of other arteries. Normalization of the blood pressure following
      PTRA in both and an uncomplicated course after a surgical myocardial
      revascularization in one of them illustrates the importance of renal
      revascularization. Pulmonary oedema occurred preoperatively in four out of 30
      patients with abdominal aortic aneurysm in whom significant renal artery stenoses
      coexisted. Two patients died despite surgery, one patient is clinically stable
      and the medicament treatment of heart failure is inevitable in the fourth with a
      left ventricular aneurysm following myocardial infarction. The occurrence or
      recurrence of pulmonary oedema in the absence of other explanation should suggest
      the possibility of bilateral or unilateral renal artery stenosis requiring renal
      revascularization for blood pressure regulation as well as for elimination of
      other manifestations/complications.

PMID- 14692126
TI  - [Cystatin C as a measure of glomerular filtration in patients with kidney
      transplants].
AB  - INTRODUCTION: Assessment of renal function is of great importance in clinical
      medicine, especially in renal transplant patients requiring frequent controls of
      renal function. Therefore, continuous efforts have been made in searching precise
      and simple method for determination of glomerular filtration rate (GFR). Serum
      level of cystatin C (CyC), protein of low molecular weight, has been proposed as
      measure of GFR, but the data of its value in renal transplant patients are scarce
      [8-10]. PURPOSE: The aim of this study was to compare the serum levels of low
      molecular weight proteins CyC and beta 2-microglobulin (beta 2-MG) with
      creatinine clearance, as well known measure of GFR, in renal transplant patients
      and control group of patients with different renal disease. PATIENTS AND METHODS:
      The study included 36 patients divided into two groups. Group 1: 20 renal
      transplant patients (12 men and 8 women) aged between 22 and 63 (40.4 +/- 10.1)
      years with creatinine clearance from 7.1 to 77.7 ml/min. Group 2: 16 controls (5
      men and 11 women) with various renal diseases, aged between 24 and 63 (41.5 +/-
      12.5) years with creatinine clearance from 60.5 to 116.8 ml/min. N Latex Cystatin
      C and beta 2-microglobulin for the Behring Nephelometer System was used in this
      study. Creatinine was determined with Jaffe-reaction in serum and urine. RESULTS:
      In renal transplant patients as well as in control group of patients the
      significant correlation between creatinine clearance and reciprocal values of the
      serum CyC (rt = 0.828; pt < 0.001; rc = 0.603; pc < 0.05) and reciprocal values
      of the serum beta 2-MG levels (rt = 0.791; pt < 0.001; rc = 0.627; pc < 0.05) was
      found (Graph 1). There was a slightly better correlation between creatinine
      clearance and reciprocal values of the serum CyC than the one between creatinine
      clearance and reciprocal values of the serum beta 2-MG without statistical
      significance in renal transplant patients. There was no difference in correlation
      coefficients between both low molecular weight proteins and creatinine clearance
      in Group 2. The correlation coefficient between serum CyC and beta 2-MG was r =
      0.839 (p < 0.001) in renal transplant patients and r = 0.835 (p < 0.05) in
      control group. There were no significant differences in correlation coefficients
      between reciprocal values of serum CyC and creatinine clearance (p = 0.2043) as
      well as reciprocal values of serum beta 2-MG and creatinine clearance (p =
      0.3717) between Group 1 and Group 2. DISCUSSION: In renal transplant patients
      rapid assessment of graft function is necessary. This allows early recognition of
      rejection as well as differential diagnosis of different renal graft disorders.
      Study of Risch and co [16] suggested that serum CyC was very good marker for GFR
      in renal transplant patients which was confirmed by the other authors too [20
      22]. During inflammatory process or other pathological conditions, especially
      during acute rejection or infections. CyC also provided precise assessment of GFR
      while creatinine clearance varied dramatically [16]. Serum concentration of beta
      2-MG, another low molecular weight protein, also depends both on its production
      rate and the GFR [5, 19]. Its production is dramatically different in patients
      with infections [5] as well as while immunosuppressive drugs are used [16].
      Therefore, beta 2-MG is impractical as GFR marker in patients with renal
      transplants. So, serum CyC was considered as better marker for GFR than beta 2-MG
      and creatinine clearance in renal transplant patients with different
      complications [16]. In this study serum CyC was slightly better marker for GFR
      than beta 2-MG, without statistical significance (Graph 1). Renal transplant
      patients, however, were in the stable condition at the time of the study.
      CONCLUSION: Serum CyC was moderately better marker of GFR than beta 2-MG in renal
      transplant patients when they were in the stable condition. Serum CyC and beta 2
      MG were the same markers of GFR in control group of patients with various renal
      diseases. There was no significant difference in correlation coefficients between
      reciprocal values of the serum CyC and creatinine clearance (p = 0.2043) as well
      as reciprocal values of the serum beta 2-MG levels and creatinine clearance (p =
      0.3717) between two examined groups of patients. The studies on renal transplant
      patients with acute graft rejection or infections are warranted.

PMID- 14692127
TI  - [Vascular complications after kidney transplantation].
AB  - INTRODUCTION: Despite high graft and recipient survival figures worldwide today,
      a variety of technical complications can threaten the transplant in the
      postoperative period. Vascular complications are commonly related to technical
      problems in establishing vascular continuity or to damage that occurs during
      donor nephrectomy or preservation [13]. AIM: The aim of the presenting study is
      to evaluate counts and rates of vascular complications after renal
      transplantation and to compare the outcome by donor type. MATERIAL AND METHODS: A
      total of 463 kidneys (319 from living related donor--LD and 144 from cadaveric
      donor--CD) were transplanted during the period between June 1975 and December
      1998 at the Urology & Nephrology Institute of Clinical Centre of Serbia in
      Belgrade. Average recipients' age was 33.7 years (15-54) in LD group and 39.8 (19
      62) in CD group. Retrospectively, we analyzed medical records of all recipients.
      Statistical analysis is estimated using Hi-squared test and Fischer's test of
      exact probability. RESULTS: Major vascular complications including vascular
      anastomosis thrombosis, internal iliac artery stenosis, internal iliac artery
      rupture, obliterant vasculitis and external iliac vein rupture were analyzed. In
      25 recipients (5.4%) some of major vascular complications were detected. Among
      these cases, 22 of them were from CD group vs. three from LD group. Relative rate
      of these complications was higher in CD group vs. LD group (p < 0.0001). Among
      these complications dominant one was vascular anastomosis thrombosis which
      occurred in 18 recipients (17 from CD vs. one from LD). Of these recipients 16
      from CD lost the graft, while the rest of two (one from each group) had lethal
      outcome. DISCUSSION: Thrombosis of renal allograft vascular anastomosis site is
      the most severe complication following renal transplantation. In the literature,
      renal allograft thrombosis is reported with different incidence rates, from 0.5
      4% [14, 15, 16]. Data from the present study demonstrate that the rate of this
      complication in LD group was low, only 0.3%, but significantly higher in CD group
      -11.8%. Many factors should be considered in order to understand for such
      significant difference among these groups. First of all, cadaveric transplant
      activity in our country is very low. In our series, median waiting period for
      renal transplantation was 2.8 years in LD group vs. 4.8 years in CD group (p <
      0.01). Also, vascular damages because of long term hemodialysis are contributing
      factors. Mean age of CD recipients was 7.4 years bigger vs. LD recipients.
      Primary cadaveric graft damage by accident and further manipulations during
      cadaveric donor nephrectomy, preservation and perfusion are additional factors
      compromising the quality of cadaveric renal transplant outcome. Also,
      preoperative evaluation of cadaveric grafts is not as exact as in cases of LD
      grafts (excretory urography, arteriography, etc). In the available transplant
      literature it is almost impossible to find data about vascular complications by
      different donor types. Mostly, authors offer experiences related to all
      transplants and most of them agree that in the present time better results are
      obtained using living donors [17].

PMID- 14692128
TI  - [Clinical characteristics of the tympanic membrane retraction pocket].
AB  - Development of the eardrum retraction pocket, as pathologic finding, depends on
      Eustachian tube dysfunction, onset of the middle ear infection and site of
      development of retraction on the eardrum. The study is aimed at: 1. Determining
      the incidence of eardrum retraction pocket and cholesteatoma within it, as well
      as at the degree of eardrum retraction; 2. Determining of association between
      eardrum retraction pocket and changes of the eardrum mucosa and pars tensa of the
      tympanic membrane; 3. Determining of onset and intensity of the bone destruction
      in eardrum retraction pocket; 4. Examining of Eustachian tube function based on
      time of mucocilliary transport according to the type of the eardrum retraction
      pocket. The study is based on the retrospective analysis of the results obtained
      from the patients treated at the Institute of Oto-Rhino-Laryngology and
      Maxillofacial Surgery, Clinical Centre of Serbia in Belgrade for the diagnosis of
      the chronic suppurative otitis who underwent otosurgical procedures during the
      six-year period, from 1996-2001. In our series of 540 patients subjected to
      otosurgical treatment, the incidence of the retraction pocket of the eardrum was
      11.23%. Onset of more severe degree of eardrum retraction was most frequent in
      the attic. Cholesteatoma was detected in 82.2% of patients of the group with the
      attic-retraction pocket of the eardrum, as well as in 25% of patients of the
      group of tensa-sinus retraction pocket of the eardrum. Atrophic changes of the
      tympanic membrane pars tensa were detected in almost all tensa-sinus retraction
      pockets of the eardrum. Approximately one half of the attic-retraction pockets of
      the eardrum were accompanied by eardrum atrophy. Bone destruction of the auditory
      ossicles was limited to the long process of incus and superior structures of
      stapes. Time of the mucocilliary transport was significantly longer (p < 0.01) in
      attic-retraction pocket of the eardrum than in tensa-sinus retraction pocket of
      the eardrum, indicating significance of tube in development of attic-retraction
      pocket of the tympanic membrane. Reversible changes of the middle ear mucosa were
      evidenced in three quarters of the tensa-sinus retraction pockets of the eardrum
      indicating that inflammation is the major factor influencing onset of tensa-sinus
      retraction pocket of the eardrum.

PMID- 14692129
TI  - [Craniospinal radiotherapy in combined therapy of medulloblastoma in children and
      adolescents].
AB  - PURPOSE: The aim of this study was: 1. to evaluate treatment results of combined
      therapy (surgery, postoperative craniospinal radiotherapy with or without
      chemotherapy) and 2. to assess factors affecting prognosis (extend of tumor
      removal, involvement of the brain stem, extent of disease, postoperative
      meningitis, shunt placement, age, sex and time interval from surgery to start of
      postoperative radiotherapy). PATIENTS AND METHODS: During the period 1986-1996,
      78 patients with medulloblastoma, aged 1-22 years (median 8.6 years), were
      treated with combined modality therapy and 72 of them were evaluable for the
      study endpoints. Entry criteria were histologically proven diagnosis, age under
      22 years, and no history of previous malignant disease. The main characteristics
      of the group are shown in Table 1. Twenty-nine patients (37.2%) have total, 8
      (10.3%) near total and 41 (52.5%) partial removal. Seventy-two of 78 patients
      were treated with curative intent and received postoperative craniospinal
      irradiation. Radiotherapy started 13-285 days after surgery (median 36 days).
      Only 13 patients started radiotherapy after 60 days following surgery. Adjuvant
      chemotherapy was applied in 63 (80.7%) patients. The majority of them (46; 73%)
      received chemotherapy with CCNU and Vincristine. The survival rates were
      calculated with the Kaplan-Meier method and the differences in survival were
      analyzed using the Wilcoxon test and log-rank test. RESULTS: The follow-up period
      ranged from 1-12 years (median 3 years). Five-year overall survival (OS) was 51%
      and disease-free survival (DFS) 47% (Graph 1). During follow-up 32 relapses
      occurred. Patients having no brain stem infiltration had significantly better
      survival (p = 0.0023) (Graph 2). Patients with positive myelographic findings had
      significantly poorer survival compared to dose with negative myelographic
      findings (p = 0.0116). Significantly poorer survival was found in patients with
      meningitis developing in the postoperative period, with no patient living longer
      than two years (p = 0.0134) (Graph 3). By analysis of OS and DFS in relation to
      presence of the malignant cells in liquor, statistically significant difference,
      i.e. positive CSF cytology was not obtained, which was of statistical importance
      for survival (p = 0.8207). Neither shunt placement nor shunt type showed any
      impact on survival (p = 0.5307 and 0.7119, respectively). Children younger than
      three years had significantly poorer survival compared to those older than 16
      years (p = 0.0473). Although there was a better survival rate in females than in
      males this was not statistically significant (p = 0.2386). The analysis results
      of treatment showed that significantly better survival occurred in patients in
      whom total or subtotal tumor removal was possible (p = 0.0022) (Graph 4).
      Patients who started radiotherapy within two months after surgery have better
      survival, but again this was not statistically significant, probably due to the
      small number of patients receiving delayed radiotherapy (p = 0.2231) (Graph 5).
      CONCLUSION: Based on this factors standard and high risk group could be defined.
      Combined chemotherapy should to be investigated particularly for high risk
      subgroup. Future research should be done to define new therapeutic modalities
      (gene therapy, compounds active in tumor antiangiogenesis etc).

PMID- 14692130
TI  - [Advantage of combined spinal, epidural and general anesthesia in comparison to
      general anesthesia in abdominal surgery].
AB  - Type and technique of anesthesia have an important effect on per operative
      surgical course. The aim of the study was prospective analyses of advantages of
      combined spinal, epidural and general anesthesia (CSEGA) versus general
      anesthesia (GA) in abdominal surgery according to: 1. operative course
      (haemodynamic stability of patients, quality of analgesia, undesirables effects),
      2. postoperative course (quality of analgesia, unfavourable effects, temporary
      abode of patients in intensive care). Using prospective randomized double blind
      controlled study, we evaluated two groups of patients whom the same type of
      abdominal surgical intervention was planed and the only difference was the type
      of technique of anesthesia. First group of patients (n = 34), was treated with
      CSEGA and second group of patients (n = 33), was treated only with standard (GA).
      Both groups had intraoperative and 24-hour-long postoperative continued
      monitoring of blood pressure, central venous pressure, and dieresis. In the 24
      hours postoperative period, the following parameters were analyzed: vigilance
      conditions, motor block level, pain intensity in rest and movement, necessity for
      a complementary analgesia, side effects and final subjective effect of analgesia.
      There was important difference in waking up the patients after a general
      anesthesia--in the first group this period was shorter. In the first 24 hours,
      patients from the first group didn't get any systemic analgesic, while the
      patients from the second group needed fractionary application of parenteral
      analgesics in the period of 4-6 hours. Patients from the first group were also
      physically faster and easier recovered and they had less respiratory
      complications and there was not any example of thromboembolsm and the intestine
      motility was faster re-established. First group of patients spent less time in
      intensive care (three days) than second group (six days). Final subjective effect
      of analgesia, according to verbal descriptive scale (VDS) of pain was satisfying
      with 75% of patients of the first group and 15% of patients of the second group.
      According to results investigation, advantages of CSEDGA versus GA in abdominal
      surgery manifold: better hemodynamic stability and perfusion of operative region,
      decrease of single doses of opioid analgesics, local and general anesthetics
      followed by the decrease of their side effects, better intensity and longer
      duration of analgesia, improved total functional capability of patients.

PMID- 14692131
TI  - [Characteristics and habits of parents of children with insulin-dependent
      diabetes mellitus].
AB  - The aim of this case-control study conducted in Belgrade during 1994-1997 was to
      investigate whether parental demographic characteristics and habits are
      associated with insulin-dependent diabetes mellitus (IDDM). Case group comprised
      105 children up to 16 years old with IDDM and control group comprised 210
      children with skin diseases. Cases and controls were individually matched by age
      (+/- one year), sex and place of residence (Belgrade). According to chi 2 test
      results, children with IDDM significantly had five or more family members and
      they also significantly more frequently had poor socio-economic status than their
      controls. Higher education of fathers was significantly more frequently reported
      in diabetic children, in comparison with their controls. Parents of diabetic
      children were significantly more frequently occupationally exposed to radiation,
      petroleum, and its derivates, organic solvents, dyes and lacquers. During
      pregnancy mothers of diabetic children significantly more frequently smoked
      cigarettes and consumed coffee, coca-cola, alcohol and foods containing
      nitrosamines. Fathers of diabetic children more frequently consumed alcohol.

PMID- 14692132
TI  - [Factors which could affect the severity of post-traumatic pulmonary fat embolism
      -a prospective histological study].
AB  - INTRODUCTION: Each fracture of long or pelvic bones as well as large contusions
      of subcutaneous fat tissue cause releasing of fat globules that rapidly penetrate
      into circulation through the ruptured veins of the injured tissue, and reach the
      lung circulation [1,2]. During the first phase, fat emboli block the functional
      lung circulation by their mechanical effect in capillaries producing so called
      isolated post-traumatic lung fat embolism [3]. The surface layer of a fat
      embolus, which is practically in liquid state, behaves as a membrane of very high
      density, i.e., as it is under high pressure which obstruct the blood stream [4]
      that is finally stopped at the level of lung blood vessels with diameter of
      approximately 20 mu [5]. This pathophysiological mechanism produces cor pulmonale
      acutum, with poor pathological findings [8]. Nowadays, the post-mortem diagnosis
      of lung fat embolism is based on microscopical examination of tissue specimens,
      usually prepared with special histological staining (Sudan III) [9]. The grading
      of fat embolism according to Sevitt's criteria is generally accepted [10]. Taking
      of slices from apicoventral areas of the lungs has been recommended [11]. With
      longer outliving period, the total number of fat emboli in the lung circulation
      gradually decreases, due to their disintegration and resorption. It has been
      stated that fat globules completely disappear about 4-6 weeks after injury, and
      that they should not be searched for microscopically in this post-traumatic phase
      [11]. OBJECTIVES: The aim of our work was to determine whether the age of
      injured, their gender, total severity of trauma, outliving period, and
      hypovolemic shock that develops after injuring, may induce development of more
      severe forms of post-traumatic lung fat embolism. MATERIAL AND METHODS: A
      prospective histological study was performed on the autopsy material of the
      Institute of Forensic Medicine in Belgrade. The analyzed sample consisted of
      individuals with injuries that might be a source of fat emboli (fractures of long
      bones, large contusions of subcutaneous fat tissue). The lung slices were
      systematically taken and stained with special fat staining (Sudan III). In each
      particular case, the grade of lung fat embolism was counted on the basis of
      microscopical appearance, according to Sevitt's criteria. The total severity of
      trauma was estimated by calculation of the Injury Severity Score (ISS) [13, 14].
      In no cases from the analyzed sample, the fat embolism was mentioned as either
      singular or plural cause of death. The obtained results were analyzed by means of
      appropriates statistical methods (ANOVA, LSD-test, chi 2 test. Man-Whitney test,
      Fischer's test of correct probability). RESULTS AND DISCUSSION: The analyzed
      sample included 58 fatally injured individuals, 39 males and 19 females. The
      average age was 54.10 years (SD = 16.56), the average value of ISS was 34.69 (SD
      = 5.88), and the average outliving period was 3.74 days (SD = 5.88). However, all
      these data look differently when the analyzed sample has been stratified and
      analyzed according to the estimated grade of lung fat embolism. It was not showed
      that severity of lung fat embolism depends on sex of the injured (chi 2 = 0.842;
      p > 0.05). The groups with the slightest and the most severe grade of lung fat
      embolism are statistically significantly different in relation to age of
      individuals (ANOVA, p = 0.017). By means of LSD test, it has been showed that the
      group with the most severe grade of lung fat embolism (grade III) is
      statistically significantly different comparing to other two groups (with grade I
      and II) in relation to the age of injured (the values are p = 0.16 and p = 0.19
      respectively, and the both groups are less than p = 0.05). In the group with the
      most severe grade of lung fat embolism, the older individuals are statistically
      significantly represented comparing to other two groups. CONCLUSION: The analysis
      of our sample showed that the most severe grade of post-traumatic lung fat
      embolism (microscopical grade III according to Sevitt's criteria) was determined
      in older individuals, more severely injured, and with shorter outliving period.
      The severity of fat embolism depends neither on sex of the injured, nor on
      development of post-traumatic hypovolemic shock. The obtained results related to
      the influence of hypovolemic shock on severity of fat embolism should be accepted
      with a caution. Namely, sometimes there is an intention to simplify a procedure
      of creating of autopsy conclusion about the cause of death, so that loss of blood
      is not mentioned at all, in spite of fact that it could have been a concurrent
      cause of death, while in other cases exsanguination is designated as a sole cause
      of death, forgetting the possibility that fat embolism could have really been the
      immediate cause of death.

PMID- 14692133
TI  - [Agranulocytosis and acute coronary syndrome in apathetic hyperthyroidism].
AB  - INTRODUCTION: Tissue expose to excessive levels of circulating thyroid hormones
      results in thyrotoxicosis. In most cases, thyrotoxicosis is due to hyperactivity
      of the thyroid gland. Cardiovascular and myopathic manifestations are predominant
      clinical features in most hyperthyroid patients, aged 60 years and older. Some of
      patients have apathetic hyperthyroidism which presents with weight loss, small
      goiter, severe depression and without clinical features of increased sympathetic
      activity [3, 6]. About 50% of patients with cardiovascular manifestations have no
      evidence of underlying heart disease. Cardiac problems resolve when euthyroid
      state is established [3]. Three treatment modalities are available in
      hyperthyroidism, namely medicament therapy, surgery and radioactive iodine.
      Antithyroid drug therapy complications, can be mild such as rash, which is
      managed without cessation of therapy by antihistamines administration. On the
      other hand, very serious complications such as agranulocytosis, necessitate
      immediate discontinuation of the medication and appropriate treatment. Although
      extremely rear, it is life-threatening with highly variable recovery time. CASE
      REPORT: A 62-year-old woman with recurrent hyperthyroidism was admitted after
      treatment of agranulocytosis due to antithyroid drugs in another institution with
      G-CSF. The patient presented with clinical features of apathetic hyperthyroidism
      with extremely elevated thyroid hormone levels (total and free T4) and suppressed
      TSH. Radioactive iodine (5 mCi) was administered after increased thyroid uptake
      was confirmed. Echocardiography on admission was normal. ECG revealed moderately
      inverted T waves in standard and V1, V2 precordial leads. Laboratory analysis
      revealed mild normocytic anemia with normal white blood cell count, hypokaliemia
      and normal concentration of creatine phosphokinase, lactic dehydrogenase and
      mildly elevated aspartate transminase in sera. Chest X-ray was consistent with
      pulmonary emphysema. Because the worsening of ECG changes she was transferred to
      Coronary unit. The diagnosis of non-Q myocardial infarction was confirmed and
      treatment with nitrates and beta-adrenergic antagonists was instituted. Four
      weeks later she became euthyroid and coronarography was performed. Subepicardial
      coronary arteries were normal (Figure 1). She was dismissed, and still euthyroid
      three months later. DISCUSSION: Agranulocytosis is very rare but very serious
      complication of antithyroid drug therapy. It can be detected in about 0.1-1%
      patients during the first three months of treatment. Sudden appearance, heralded
      by sore throat and fever, prompt physicians to seek white blood cell and
      differential count [1-3]. Confirmation of diagnosis urges cessation of drug
      therapy and appropriate antibiotic treatment. Recently, it was reported that
      recombinant human granulocyte colony-stimulating factor (rhG-CSF) is to be
      effective in shortening the recovery time in the neutropenic patients undergoing
      chemotherapy and also in patients with other types of neutropenia [5]. Tamai at
      al. [7] confirmed positive outcome in 34 patients treated with rhG-CSF compared
      to corticosteroid treatment. Hematologic laboratory abnormalities disappear 7-10
      days after session of therapy. Patients completely recover two to three weeks
      later. Fatal outcome was also described [1-5]. Thyroid hormones have profound
      effects on cardiovascular physiology, especially on heart rate, cardiac output
      and systemic vascular resistance. In patients with hyperthyroidism, cardiac
      output is much higher than in normal persons. This is the result of direct effect
      of thyroid hormones on cardiac muscle contractility, heart rate and decrease in
      systemic vascular resistance. Excessive thyroid hormone secretion increases
      cardiac Na-K-activated plasma membrane ATP-ase and sarcoplasmic reticulum Ca
      activated ATP-ase with resultant in increase myocardial contractility [6, 9].
      Sinus tachycardia is the most common rhythm disorder in hyperthyroidism, but
      paroxysmal tachycardia and atrial fibrillation are not rare. This can be
      explained by increased heart rate, cardiac output, blood volume, coronary artery
      flow and peripheral oxygen consumption in thyrotoxicosis [9]. Patients with
      coronary arteriosclerosis can develop angina pectoris during thyrotoxic stage,
      which can be explained by imbalance between cardiac demand and supply. Myocardial
      damage is often in thyrotoxic patients with chronic hart failure, together with
      myocardial infarction in patients without coronary disease [2,6]. Congestive
      heart failure and atrial fibrillation are relatively resistant to digitalis
      treatment because of high metabolic turn over of medication and excessive
      myocardial irritability in hyperthyroidism [6]. Cardiovascular and myopathic
      manifestations predominate in older hyperthyroid patients (over 60 years) and
      some of them can have only few symptoms of hyperthyroidism [1-3]. Thyrotoxic
      state characterized by fatigue, apathy, extreme weakness, low-grade fever and
      sometimes congestive heart failure are designated as apathetic hyperthyroidism.
      Such patients have small goiters, mild tachycardia and often cool and dry skin
      with few eye signs [6]. Patients with subclinical hyperthyroidism are at
      increased risk for atrial fibrillation [9]. Unstable angina and non-Q myocardial
      infarction (non ST elevation) are acute manifestation of coronary artery disease.
      The acute coronary syndrome of unstable angina, non-Q myocardial infarction and Q
      wave myocardial infarction have atherosclerotic lesions of the coronary arteries
      as a common pathogenic substrate. Erosions or ruptures of unstable
      atherosclerotic plaque triggered pathophysiologic processes, resulted in thrombus
      formation at the site of arterial injury. This leads to abrupt reduction or
      cessation through the affected vessel. Clinical manifestations of unstable angina
      and non-Q myocardial infarction are similar and diagnosis of non-Q myocardial
      infarction is made on the basis of elevated serum markers indicative of cardiac
      necrosis, detected in peripheral circulation. Acute coronary syndrome ranging
      from unstable angina to myocardial infarction an non-Q myocardial infarction
      represents increasingly severe manifestations of the same pathophysiologic
      processes [10,11]. In conclusion, these 62-year-old woman presented with
      apathetic form of recurrent hyperthyroidism associated with two serious
      complications, life-threatening agranulocytosis and acute coronary syndrome.

PMID- 14692134
TI  - [Renovascular hypertension in a child with type 1 neurofibromatosis].
AB  - Arterial hypertension in pediatric patients with neurofibromatosis type 1 (NF 1)
      is usually due to renal artery stenosis (RAS) mainly involving the proximal part
      of the vessel. The treatment modalities are highly individualized. In severe
      and/or bilateral RAS, antihypertensive drugs are either ineffective or have the
      potential risk for acute renal failure, while percutaneous transluminal
      angioplasty (PTA) has limited success due to the ostial localization of RAS and
      the tough fibrotic tissue involved that is refractory to dilatation Renal
      autotransplantation has potential advantages when medical control and PTA/or
      bypass techniques failed. Here we report 5 year-old girl with NF 1 and
      hyponatremic hypertensive syndrome due to severe bilateral disease, occluded
      proximal part of the right artery and ostial stenosis (80%) of the left one. Only
      left kidney was identified on 99 m Tc DTPA, but the right one was visualized on
      the renal ultrasonography and in the late phase of arterial renography due to
      well developed collateral circulation. Multiple antihypertensive drugs
      (nifedipine, labetolol and minoxidil) in maximal doses and PTA failed to
      normalize BP while short term therapy with ACEI with NF1 and hyponatremic
      hypertensive syndrome due to severe bilateral renovascular disease; occluded
      proximal part of the right renal artery and ostial stenosis (80%) of the left
      one. Only left kidney was identified on 99 m Tc DTPA, but the right one was
      visualized on the renal ultrasonography and in the late phase of arterial
      renography due to well developed collateral circulation. Multiple
      antiphypertensive drugs (nifedipine, labetolol and minoxidil) in maximal doses
      and PTA failed to normalize BP while. short term therapy with ACEI, captopril
      induced transient acute renal failure. Autotransplantation of right kidney saved
      its function and improved BP control. Our current case Autotransplantation of
      right kidney saved its function and improved BP control. Our current case is
      illustrative for a difficult management of renovascular hypertension in children
      with NF1. This is the first and up to now the only case of autotransplantation
      performed in Yugoslavia.

PMID- 14692135
TI  - [Two cases of pancreatic head polypeptide tumors, one with a central cavity which
      fistulized into the duodenum].
AB  - PP omas are rare, usually malignant tumours of the PP cells of the Langerhan's
      islets which secrete pancreatic polypeptide. The authors present two women
      operated for PP-omas of the pancreas. The first was 55 year-old woman in whom we
      did a cephalic duodenopancreatectomy (Whipple's procedure) for the tumor of the
      head of the pancreas with central cavity containing gas due to communication with
      the duodenum. Immunohistochemistry showed a PP oma with strong generalised
      immunoreactivity with antibodies against Chromogramin A, neuron specific enolasa
      and PP with more the 95% of tumor cells and coexpression of somatostatine in 35%
      and VIP in less then 5% of tumor cells. Following uneventful recovery the patient
      stayed symptom free so far and put 20 kilograms in weight. The second patient was
      19 year-old girl with a multinodal tumor of almost the entire pancreas in whom a
      local excision of the nodal mass of the head of the pancreas had been carried out
      in the other hospital, three years ago and relaparotomy and tumor biopsy a month
      before admission to our institution. In her we did a total duodenopancreatectomy
      and standard lymphadenectomy for a multinodal mass occupying almost the entire
      pancreas. Immunohistochemistry showed a strong generalised immunoreactivity with
      antibodies against Chromographin A, Neuron specific enolasa and PP for more then
      95% of tumors, cells. Glucagon was expressed in few focuses (in less then 1% of
      cells), somatostatin was expressed very rarely in single cells while the rest of
      tumor markers did not show a visible immunologic reactions in the majority of
      tumors, cells. Three years after surgery she died due to multiple liver
      secondaries.

PMID- 14692136
TI  - [Animal models in the study of atherosclerosis].
AB  - When selecting an animal species for atherosclerosis research, the most important
      issue is matching the model to the experiment. In choosing the atherosclerosis
      model there is a wide variety of choices. Genetic hyperlipidemic disorders are
      best studied in Watanabe rabbits and in transgenic (knockout or overexpressed)
      mice. Interaction between clotting disorders and atherosclerosis can be evaluated
      in von Wilebrand's disease swine. If hypo- or hyper-responsiveness to atherogenic
      stimuli is to be investigated, one should consider the pigeons. Interactions
      between atherosclerosis and hypertension can be studied in rabbits and monkeys.
      Macaca nigra has proven to be very valuable in studies concerning the
      interactions between atherosclerosis and diabetes. Using suitable manipulation
      and other advantages, rabbits will yield significant insight into specific
      aspects of hypercholesterolemic effects and atherosclerosis.

PMID- 14692137
TI  - [Epoprostenol in the treatment of portopulmonary hypertension].
AB  - Primary or non-hemodynamic pulmonary hypertension is characterized by the
      increased pulmonary arterial pressure, higher than 3.32 kPa, and normal pulmonary
      capillary pressure less than 1.99 kPa. Primary pulmonary hypertension is a rare
      complication of portal hypertension, which significantly increases surgical
      morbidity and mortality, and it is not reversible after liver transplantation. As
      a rule, clinical manifestations of pulmonary hypertension are disguised by
      complications of portal hypertension. The symptoms of chronic pulmonary heart,
      such as peripheral edema and ascites, are usually ascribed to liver insufficiency
      and/or portal hypertension. Clinical significance of portopulmonary hypertension
      follows from the fact that the failure of the right heart is most commonly the
      direct cause of death in these patients. The majority of authors concurs that the
      right heart catheterization is the most valid method for diagnosis of
      portopulmonary hypertension. Doppler echocardiography represents quite valuable
      non-invasive diagnostic method, especially in patients with extensive spontaneous
      and surgical porto-systemic collaterals, rendering the high risk group of cases.
      Epoprostenol (prostacyclin), administered via continuous infusion, diminishes the
      platelet aggregation and causes the intense pulmonary and systemic
      vasodilatation. Good hemodynamic effect of this substance was verified in
      patients with primary pulmonary hypertension. Several articles have reported that
      long-term, continual epoprostenol administration in dose of 10 to 28 ng/kg/min.
      Has significantly reduced pulmonary vascular pressure and pulmonary vascular
      resistance. Portopulmonary hypertension represented the absolute contraindication
      for liver transplantation. Huge clinical significance of epoprostenol reflects in
      the fact that, along with the improvement of pulmonary hemodynamics, it provides
      the prerequisite for liver transplantation in patients with portopulmonary
      hypertension.

PMID- 14692138
TI  - [Autoimmune processes in diseases of the thyroid gland].
AB  - The previous knowledge related to auto-immune occurrences in thyroid gland
      disease are described in the review, showing main antigens, auto-antibodies, the
      inclusion of humoral and cellular immunity in the most frequent thyroid gland
      diseases. In spite of many learnings, which are broadened every day, the exact
      sequence of events and roles of external factors in genetically predisposed
      persons is still unknown. An identification of auto-antibodies gives direct
      evidence about the auto-immune process, as they are present among the majority of
      patients with Graves' hyperthyroid and Hashimoto's thyroiditis. Immuno globulins,
      created by plasma cells, linked with cytokinins from lymphocyte CD4 T, engage the
      cell auto-immune reaction in these diseases. Being acquainted with all events in
      the auto-immune process, we can understand better why these frequent diseases
      occur, why do they have chronic and recidivous course, why they are more frequent
      with women and within some families, and why they enable us to make a better
      diagnosis and treatment of these patients.

PMID- 14692139
TI  - [Physician founders of pediatric pulmonology in Serbia].
AB  - Initial steps in the field of pediatric pulmology in Serbia were made by the
      first Serbian pediatricians Dr. Platon Papakostopulo (1864-1915) and Dr. Milenko
      Materni (1875-1929). Later on these steps were continued by Prim Dr. Ljubomir
      Vulovic (1896-1970). Until the discovery of anti-tuberculotics, lung tuberculosis
      was one of the most frequent and most serious diseases among the adults and the
      children's population. Prof. Dr. Smilja Kostic-Joksic (1895-1981) and Prof. Dr
      Borivoje Tasovac (1907-1996) played a prominent role in the application and
      efficiency evaluation of BCG vaccines amount the Children in Sebia, along with
      the other chest disease studies. Immediately after the Second World War, Special
      Children's Hospital for Tuberculosis was set up, in 1945 in Belgrade. The
      Hospital had been successfully managed for a long period of time by Prim. Bojana
      Roknic (1900-1976). From 1960 to 1970 the Hospital was transformed in Special
      Children's Hospital for Chese Disense and Tuberculosis and was the only hospital
      in Serbia dealing with diagonistics, therapy and rehabilitation of children's
      chest diseases, before all asthma, recidive bronchitis and other chronical and
      recidive bronchopulmonal diseases. From 1970 until now on the postgraduate course
      in Pulmonology on the Faculty of Medicine, University of Belgrade, graduated over
      a hundred pediatricians.

PMID- 14692140
TI  - [The cellular immune reaction in synovial fluid lymphocytes to Ureaplasma
      antigens in patients with Reiter's syndrome].
AB  - INTRODUCTION: Reiter's syndrome (RS) is an seronegative arthritis that occurs
      after urogenital or enteric infection which in addition with occular and/or
      mucocutaneous manifestations presents complete form of disease. According to
      previous understanding arthritis in the RS is the reactive one, which means that
      it is impossible to isolate its causative agent. However, there are the more and
      more authors suggesting that arthritis in the urogenital form of disease is
      caused by the infective agent in the affected joint. This suggestion is based on
      numerous studies on the presence of Chlamydia trachomatis and Ureaplasma
      urealyticum in the inflamed joint by using new diagnostic methods in molecular
      biology published in the recent literature [1-3]. Besides, numerous studies of
      the humoral and cell-mediated immune response to "triggering" bacteria in the
      affected joint have supported previous suggestions [4-7]. Aim of the study was to
      determine whether synovial fluid T-cells specifically recognize the "triggering"
      bacteria presumably responsible for the Reiter's syndrome. METHOD: The 3H
      thymidine uptake procedure for measuring lymphocyte responses was applied to
      lymphocytes derived concurrently from synovial fluid (SF) and from peripheral
      blood (PB) [8]. Ureaplasma antigen and mitogen PHA stimulated lymphocytes in 24
      RS patients (24 PB samples, 9 SF samples) and the results were compared with
      those found in 10 patients with rheumatoid arthritis (RA) (10 PB samples, 5 SF
      samples). Preparation of ureaplasma antigen. Ureaplasma was cultured on cell-free
      liquid medium [9]. Sample of 8 ml was heat-inactivated for 15 minutes at 601C and
      permanently stirred with magnetic mixer. The sample was centrifuged at 2000 x g
      for 40 minutes and than deposits carefully carried to other sterile glass tubes
      (Corex) and recentrifuged at 9000 x g for 30 minutes. The deposit was washed 3
      times in sterile 0.9% NaCl, and final sediment was resuspended in 1.2 ml sterile
      0.9% NaCl. BACTERIOLOGY: Chlamydia trachomatis was isolated by cell culture using
      cycloheximide-treated McCoy cells [10], while Ureaplasma urealyticum was
      identified according to its biochemical properties grown on cell-free liquid
      medium [9]. RESULTS: Proliferative response of the PB lymphocytes to stimulation
      by mitogen and ureaplasma antigen did not differ between RS and RA patients.
      Also, there was no difference in proliferative response of SF lymphocytes to
      mitogen stimulation between RS and RA patients (Figure 1). However, proliferation
      of SF lymphocytes stimulated by ureaplasma antigen was significantly elevated in
      RS patients compared with the control group. This difference is statistically
      significant (p < 0.05) (Figure 2). Difference in proliferative response of the PB
      and SF lymphocytes stimulated by the ureaplasma antigen was not found in RS
      patients. DISCUSSION: It was found that SF lymphocytes of RS patients showed
      significantly elevated proliferative response to stimulation by the ureaplasma
      antigen compared with SF lymphocytes of the control group. There was no
      difference when the lymphocytes were stimulated by the mitogen. Our findings
      suggest that elevated proliferative response of lymphocytes is the sign of
      stimulation cell-mediated immunity to antigen present in inflamed joint. Hence,
      the main immune response to Ureaplasma is on the cell-mediated level in the
      affected joint. This confirms the earlier finding reported by Ford et al. who
      concluded that synovial rather than peripheral blood lymphocytes indicate the
      microbiological cause of arthritis [11, 12]. Horowitz et al. demonstrated the
      correlation between clinical remission after antibiotic therapy and eradication
      of Ureaplasma, together with a decrease in cellular immune response synovial
      fluid lymphocytes to ureaplasma antigen stimulation [13]. In that study Horowitz
      did not find statistically significant difference of ureaplasma proliferative
      response between PB and SF lymphocytes in patients with RS. We obtained the same
      results. Than we concluded that sensibilization of immune system exist in the
      presence of foreign antigen in RS patients. The other authors demonstrated higher
      stimulation indices than the ones we found in our patients [11-15]. This
      difference may be the result of different preparation of antigens, in other words
      selection of serotype of Ureaplasma for antigen preparation different conditions
      of lymphocyte cultivation. We concluded that the presence of antigen, antigen
      specific T cells and efficient antigen-presenting cells (CD4+ T cells) in the
      joint of RS patients strongly suggests that a T-cell-mediated response to
      bacteria has the central role in the pathogenesis of Reiter's syndrome.

PMID- 14692141
TI  - [IgA nephropathy: clinico-morphologic correlations].
AB  - IgA nephropathy is glomerular disease characterized by the presence of IgA
      dominant or codominant immunoglobuline deposits in glomerular mesangium which can
      be demonstrated by immunofluorescence. Clinical manifestations of IgA nephropathy
      in the majority of cases is hematuria which can be macro or microscopic, isolated
      or combined with proteinuria, which can be of nephrotic range. The prognosis of
      the disease is better if presented with haematuria. Intensity of morphologic
      changes as well as the prognosis is in correlation with the amount of
      proteinuria. The prognosis is better in children.

PMID- 14692142
TI  - [Correlation of neurodevelopmental disorders in schizophrenia].
AB  - Contemporary aetiopathogenetic considerations, based on neuro-imaging, genetic
      and developmental neurobiology studies, suggest neurodevelopmental origin of
      schizophrenia. Several lines of evidence including structural abnormalities on in
      vivo brain imaging, the excess of prenatal and obstetric complications and the
      association of congenital and minor physical anomalies with schizophrenia,
      strongly indicate the neurodevelopmental pathogenesis of schizophrenia. On the
      other hand, controversial concept of psychotic continuum suggests schizophrenia
      and depression sharing the same genetic contribution to the pathogenesis. If this
      would be the case, depression could also be considered as neurodevelopmental
      disorder. The aims of the study were to investigate the association between: a)
      pregnancy and birth complications (PBC), and b) minor physical anomalies (MPA)
      and schizophrenia or depression. Experimental groups consisted of 60
      schizophrenic, 28 major depression patients and 30 healthy controls. All patients
      were diagnosed according to DSM-IV. Schizophrenic group was divided with regard
      to PANSS score into positive (n = 32) and negative form (n = 28) subgroups. PBC
      informations were gathered from maternal recall while MPA were examined by using
      Waldrop scale for adults. The results showed that negative and positive
      schizophrenic subgroups had significantly more PBC than depressive group (p <
      0.05), as well than controls (p < 0.001; p < 0.05; respectively). There was
      nonsignificant trend for more PBC in negative than in positive subgroup. All
      schizophrenic patients had higher rates of MPA than depressives (p < 0.05). This
      trend for more MPA was not significant in comparison with healthy controls. These
      findings suggest that schizophrenia, especially its negative forms, could be
      considered as a member of the spectrum of neurodevelopmental disorders, which
      does not seem to be the case with depression. PBC and MPA could also be valuable
      in evaluation of risks for schizophrenia and possible predictive indicators of
      its development.

PMID- 14692143
TI  - [Continuous ambulatory monitoring of blood pressure and the left ventricular mass
      index in children with kidney diseases].
AB  - INTRODUCTION: Numerous epidemiological studies have shown that blood pressure
      (BP) is positively related to cardiovascular morbidity and mortality. Although
      the relationship between BP and the incidence of morbid events is consistent and
      highly significant, it is difficult to predict the absolute risk. Several studies
      have shown that the organ damage associated with hypertension correlate to a
      greater degree with 24 h average BP than with clinic BP and the most of them
      evaluated left ventricular hypertrophy in these patients. OBJECTIVE: To evaluate
      the correlation between left ventricular mass index (LVMi) and BP, BP
      variability, pulse pressure (PP), BP load and hyperbaric index (HBI). DESIGN AND
      METHODS: Ambulatory blood pressure monitoring (ABPM) was performed in 30 children
      with renal disease aged 12.7 +/- 5.5 years. Ten of them had normal renal
      function, 3 had renal transplant and 17 of them had end-stage renal disease and
      were on chronic haemodialysis. All of the patients were submitted to an
      echocardiographic evaluation and LVMi was calculated according to Penn
      convention. Ambulatory blood pressure monitoring was performed during the 24 h
      period and average values of systolic and diastolic BP were evaluated. As an
      index of variability of BP values we used standard deviation (SD) of mean.
      Evaluation of average BP values has some disadvantages--it does not take into
      account the peaks of blood pressure and the values are lower if the circadian
      rhythm of BP is preserved--for this reason BP load and HBI were evaluated as
      well. BP load represented the percentage of BPs exceeding the upper limits of
      normal and HBI the integrated area under the ambulatory BP curve. For the upper
      limits of normal was used 95th percentile from the multicenter study of German
      authors. RESULTS: There was no correlation between LVMi and evaluated parameters.
      CONCLUSIONS: The response of myocardium to chronic increase of the afterload is
      highly individual, and probably the role of genetics in this is very important.
      Echocardiography (LVMi) could not be used with certainty for the evaluation of
      ventricular mass.

PMID- 14692144
TI  - [Psychopathologic reactions in orthopedic patients].
AB  - The idea to monitor and research psychopathological responses of physically
      injured persons in a more systematic manner has come from our observation of huge
      differences in patient behavior, whose psychological responses were noticeably
      changed and often inappropriate. The behavior aberrations were all the more
      striking because we treated war-time injuries in addition to peacetime ones. Our
      sample had 175 patient subjects, of both sexes, different ages, marital status
      and professions. A group of 70 patients treated in the Institute for Orthopedic
      Surgery and Traumatology were divided into two subgroups. The first experimental
      subgroup (E1) consisted of 26 (37.1%) patients physically injured in combat. The
      second subgroup (E2) had 44 (62.9%) patients physically injured in peacetime
      circumstances (car accidents, work accidents, etc). The physical injuries
      encompassed injuries to spinal column and extremities. The control (K) consisted
      of 105 subjects without physical injuries. The clinical picture and psychological
      reactions of the patients were examined by means of 4 instruments--PTSD-10 scale
      or posttraumatic symptoms scale [1], Family Homogeneity Index/FHI/with 19
      variables, applied to measure the relation between the family system homogeneity
      and accident effects [2], Short Eysenck's Personality Inventory applied to
      investigate neuroticism and extroversion and introversion traits [3], Late
      Effects of Accidental Injury Questionnaire [4]. Our observations of psychological
      responses of patients in our ward (insomnia, sedatives intake) were mostly
      confirmed by tests conducted with the above instruments. In the group of the
      wartime injured (E1), as well as in the control (K), Eysenck's scale proved a
      significantly higher degree of neuroticism in comparison to the peacetime
      injured. Such results indicated that the wartime injured would most probably
      develop the picture of Posttraumatic Stress Disorder. Such a conclusion was
      related not only to the seriousness of injuries but also to the circumstances of
      their occurrence. The proneness to develop PTSD symptoms was not in correlation
      with the preparedness for accident, it being much poorer in peace-time injuries,
      as opposed to wartime patients, who had been prepared to the possibility of
      injury occurrence. The highest value of family homogeneity (FHI) was established
      in the wartime injured, which led us to conclude that the injury contributed to
      the cohesion of the family from which the patient came. By extracting some
      questions related to psychopathological entities such as insomnia, depression,
      somatization, anxiety, and cognitive disorders, the following results were
      obtained. Depression was the most frequent in both groups of injuries. Anxiety
      was also present in the control group; and insomnia and somatization, that is,
      conversion symptoms, were present in both groups of the injured. By examining
      narrower psychological characteristics of the wartime injured revealed
      dissociation problems--derangement to be the most frequent. Then follow the
      symptoms of depression, which occur significantly more frequently in the wartime
      injured in comparison to the peacetime injured. The phenomenological symptoms of
      derangement and depression proved to be reliable parameters of physical trauma.
      It is also significant that the three characteristics showed correlation to
      psychopathological responses: severity of surgery, paralysis, and acute injury.

PMID- 14692145
TI  - [Correlation analysis of predictive factors of successful implantation in
      fertilization in vitro].
AB  - INTRODUCTION: Endometrial receptivity as isolated predictive factor of successful
      implantation, with its specifity is determined with numbered factors. PURPOSE:
      Purpose of this study was to evaluate significance and correlation between
      relevant factors using appropriate statistical analyses on term of embryo
      implantation. MATERIAL AND METHODS: Evaluated group contained 85 women whom
      according different causes of infertility have been determined for assisted
      reproduction program. Analysed measurements were: endometrial thickness, assessed
      hyperechogenity in relation with absolute endometrial thickness (HEA relation)
      and uterine blood flow (pulsatile index-Pi). Simultaneously were analyzed serum
      estradiol (E2; pg/ml) and progesterone (P; nmol/l) levels. After these
      evaluations achieved results were processed with standard statistical pack.
      Beside that were applied parameter and nonparameter tests with aim to test
      significancy of difference and multiple regressive analyse (Stepwise). RESULTS:
      Resulted measured parameters have been presented in basic analyse as middle value
      (Xrs) from all measurements + SD (standard deviation) and significance of
      difference is tested by mentioned statistical tests (Table 1). Application of
      Stepwise analyse, "step by step", has used parameter by parameter based on value
      which has decreased variability and based on achieved correlative coefficient
      between dependent uneven and complex of independent uneven values. This procedure
      confirms best correlation between HEA relation and serum progesterone levels and
      HEA relation in correlation with associated values: P, E2 and endometrial
      thickness (Table 1). DISCUSSION: Investigation provided till now shows that
      embryo quality and endometrial receptivity with highest probability determine
      success of applied assisted reproduction, successful embryonal implantation There
      is assessed influence of endometrial receptivity represented trough HEA relation
      using many folded regressive analyse where qualitative endometrial value has been
      looked with dependency with other parameters gives picture for high determinancy
      with hormonal activity and with stimulative ovarian activity. This determinancy
      could be viewed mostly through serum progesterone levels on day of HCG
      administration. Correlative relation between qualitative endometrial
      characteristics on day of HCG administration has high value related to
      progesterone levels. CONCLUSION: Results presented with this research confirm
      once again complexity characteristic for factors that play final role in embryo
      implantation in IVF program. There is presented only one aspect related with this
      problem with aim to contribute quantification importance and assessment rate of
      mutual influence these factors known till now as relevant.

PMID- 14692146
TI  - [Long-term results of treatment of injuries of the sectoral and segmental bile
      ducts].
AB  - INTRODUCTION: Surgically important variations of the sectoral and segmental bile
      ducts of the right lobe of the liver appear in a significant proportion of
      patients. Frequency of the injuries to these ducts is not known as the ligature
      of small ducts may pass without major consequences. MATERIAL AND METHODS: Over a
      27 year period (1. Jan 1974-31. Dec 2001) along with 168 patients with benign
      biliary strictures of type I, II, III and IV according to Bismuth's
      classification, we treated 13 patients with operative sectoral or segmental bile
      duct injuries, four patients from our institution and nine patients transferred
      from elsewhere. The injury was recognized at original surgery in all four
      patients operated in our institution. Primary repair was performed in three
      patients, in two patients direct end-to-end repair over T-tube and in one patient
      with anastomosis between the injured duct and Roux-en-Y jejunal limb, while in
      one patient the injured duct was ligated. In no one of nine patients transferred
      from elsewhere the injury was recognized during original surgery. Four patients
      were sent with biliary peritonitis, another four patients with external biliary
      fistula and one patient for pain and fever due to liver abscess. RESULTS: All
      three patients in whom the primary repair was performed had a quick and
      uneventful recovery and they stayed symptom-free so far. The patient in whom the
      injured duct was ligated died after series of complications. Four patient sent to
      us with biliary peritonitis were treated with relaparotomy, lavage and drainage
      and all developed external biliary fistula. Three of these patients had their
      fistula ceased spontaneously within few weeks, while in one patient the fistula
      didn't show signs of ceasing so that injured duct had to be anastomosed with Roux
      en-Y jejunal limb. Two out of four patients sent for external biliary fistula had
      it ceased spontaneously, while in two patients anastomosis between duct and Roux
      en-Y jejunal limb was necessary. The last, 13th patient, who had sectoral duct
      severed and ligated was reoperated, liver abscess drained and duct anastomosed
      with Roux-en-Y jejunal limb. That patient developed an anastomotic stricture a
      year later and he was successfully reoperated and stayed symptom-free so far. All
      12 patients have been followed up from nine months to 27 years (average 9.2
      years) and neither developed biliary symptoms. CONCLUSION: We conclude that the
      management of these injuries depends upon the time of recognition of the lesion,
      size of the injured duct and of the type and stage of complications.

PMID- 14692147
TI  - [Surgical treatment of polypoid lesions of gallbladder].
AB  - INTRODUCTION: Polypoid lesions of the gallbladder can be divided into benign and
      malignant categories. Malignant polypoid lesions include carcinomas of the
      gallbladder, which is the fifth most common malignancy of the gastrointestinal
      tract and the most common malignancy of the biliary tract. Benign polypoid
      lesions of the gallbladder are divided into true tumors and pseudotumors.
      Pseudotumors account for most of polypoid lesions of the gallbladder, and include
      polyps, hyperplasia, and other miscellaneous lesions. Adenomas are the most
      common benign neoplasms of the gallbladder. Cholesterol polyps are the most
      common pseudotumors of the gallbladder. The polyps can be single or multiple,
      usually less than 10 mm in size. They have no predilection for any particular
      gallbladder site, and usually are attached to the gallbladder wall by a delicate,
      narrow pedicle. No malignant potential has been identified for this type of
      pseudotumor. Adenomas are the most common benign neoplasms of the gallbladder.
      They have no predilection site in the gallbladder, and may also be associated
      with gallstones or cholecystitis. The premalignant nature of adenomas remains
      controversial. Ultrasonography (US) has been demonstrated to be significantly
      better in detecting polypoid lesions of the gallbladder as compared with computed
      tomography and cholecystography. A mass fixed to the gallbladder wall of normal
      thickness, without shadowing, is seen in case of gallbladder polyp. Since
      gallbladder cancers usually present as polypoid lesions, differentiation between
      benign polypoid lesion and malignant lesion can be very difficult, even with high
      resolution imaging techniques. PATIENTS AND METHODS: Retrospectively we have
      analyzed 38 patients with ultrasonographically detected gallbladder polyps during
      the period from January 1995 to December 2000, who were treated at surgical
      department of Health Centre in Uzice and at Surgical clinic of Clinical Centre in
      Nis. We have analyzed patients demographical data as well as their symptoms and
      radiographic findings. If the patient was operated, pathohistological findings
      were analyzed also. RESULTS: In our study 38 examined patients had mean age of
      53.2 years (standard deviation of 12.8 years; range 26-80 years). The male-female
      ratio was 1:1. Overall 36 patients had symptoms that could be related to
      gallbladder diseases. Among these patients, 32 had pain in the upper-right
      quadrant of the abdomen that could be defined as biliar colic, and two had
      symptoms of acute cholecystitis. Among remaining four patients, two were examined
      because of the pain in the lower part of the abdomen. One patient had high
      temperature of unknown origin and the gallbladder polyp was detected accidentally
      during the ultrasonographic examination of the abdomen. Second patient had
      jaundice of unknown origin, with ultrasound showing no significant changes in
      biliary tract. Preoperative ultrasound findings were inconsistent. The size of
      the lesion was marked only in 18 out of 38 patients. Among 34 operated patients,
      just 11 of them had pathohistologically verified polipoid lesion.
      Pathohistological analyzes of extirpated gallbladders showed one normal
      gallbladder, seven cholesterol polyps, one polipoid cholecystitis, and two real
      gallbladder neoplasms. One patient had gallbladder adenoma while the other had
      adenocarcinoma. Malignancy rate was 2.94% (one in 34). All patients with
      neoplastic polyps had solitary lesion larger than 1 cm in diameter, while the
      patients with non-neoplastic lesions had multiple lesions smaller than 1 cm in
      diameter. All operated patients, with the exception of one, had pathologically
      verified abnormal gallbladders. This results showed the presence of chronic
      cholecystitis even in the absence of the polyps. DISCUSSION: Generally, no
      treatment is required in young patients with very small gallbladder polyps who
      are completely free from any symptoms. A patient with dyseptic symptoms but no
      painful episodes consistent with biliary colic should be managed conservatively.
      Cholecystectomy is also indicated in patients with large gallbladder polyps size
      over 10 mm, irrespective of symptomatology. In patients with gallbladder polypoid
      lesions smaller than 10 mm, cholecystectomy is indicated only if complicating
      factors are present, e.g., age over 50 years and coexistence of gallstones. If
      the gallbladder polyp is smaller than 10 mm and complicating factors are absent,
      the "watch-and-wait" strategy seems to be recommendable. CONCLUSION: Although
      gallbladder polyps are rare, they represent a significant health problem because
      they may be a precursor to gallbladder cancer. On the basis of the available
      data, and the results that we have gained in our study we suggest that
      gallbladder should be extirpated in cases when: 1. symptomatic lesions are
      present regardless of size; 2. polyps larger than 10 mm are present because they
      represent a risk for gallbladder cancer; 3. polyps are showing rapid increase in
      size. Polyps less than 10 mm that are incidentally identified and not removed
      should be assessed by ultrasonography at least every six months. This is
      especially critical for sessile polyps, in which the possibility of a small
      cancerous polyp is greater than in pedunculated polyps. Also, asymptomatic
      lesions less than 10 mm in diameter should be removed if patient is older than 50
      years or if he has concomitant gallbladder calculosis.

PMID- 14692148
TI  - [Intravascular lymphoma of the central nervous system].
AB  - Intravascular lymphomatosis is an uncommon lymphoproliferative disorder
      characterised by intravascular distribution of neoplastic lymphoid cells (B- or T
      lymphocites), what leads to occlusion of small vessels and causes signs and
      symptoms of disorder. Its initial predilection sites are the brain or the skin,
      and hematopoetic organs are usually spared. The signs and symptoms of the
      disorder are attributed to vascular occlusion. Clinical course is fatal, besides
      therapy. In our case disorder has started with partial epileptic seizures with
      secundar generalisation, and after that with motor aphasia, right hemiparesis,
      urinary incontinence and cognitive changes. She was hospitalized for several
      times, completely investigated, but with no conclusion. Seven months after
      apperance of symptoms, she died. And diagnosis was determined at autopsy. A
      myriad of neurological and systemic manifestations are putting us in an unequal
      position with this fatal disease. Early diagnosis can increase survival and
      decrease intensity of symptoms. So every new case is important as warning that we
      must not forget about this disease.

PMID- 14692149
TI  - [Echinococcosis damaging the junction of the hepatic duct and causing severe
      obstructive icterus].
AB  - Complications of the hydatid cyst of the liver on bile ducts appear in 5-25%
      representing almost two third of all complications of the hydatid liver cysts.
      Fortunately a damage to the bile ducts causes only an infection of the cyst
      usually without major consequences. More serious complications such as
      cholangitis and deep obstructive jaundice are much rarer. The defect of the bile
      duct usually is a periferal one. Damage to the major ducts are rarer and those on
      the confluence of hepatic ducts itself are the rarity. In that case biliary
      reconstruction may be a serious challenge. The authors present a 23 year-old man
      in whom a centrally localised hydatid cyst made a major damage of the confluence
      of all three hepatic ducts causing deep obstructive jaundice. After standard
      procedure for hydatid cyst an intracavital mucosa to mucosa hepaticojejunostomy
      was carried out with excellent success. More then six years after surgery the
      patient stayed symptom-free with bilirubin and alkaline phosphatase within normal
      limits.

PMID- 14692150
TI  - [An accident after an accident--an unusual death in a hospitalized patient].
AB  - The authors present a case of accidental fatal laryngopharyngeal obstruction with
      bolus of food, in hospital, in a patient who has been treated for twenty days
      because of injuries sustained in a traffic accident. The injuries were multiple
      fractures and brain contusions that were not clinically diagnosed, while their
      symptomatology (somnolence) was attributed to morbous lesions--multifocal brain
      infarction. Mechanical asphyxiation and death occurred when the patient was fed
      in hospital by his brother. Unofficially we got an information that whole event
      was very dramatical, and that medical staff tried to attempt resuscitative
      measures, but without any written note about that in medical documentation. The
      terminal phase of his chronic desompensated cardiomyopathia was clinically
      announced as a cause of death. For forensic pathologists it was relatively easy
      task to prove mechanical asphyxiation due to laringopharyngeal blockage as a real
      cause of death on medicolegal autopsy.

PMID- 14692151
TI  - [Thrombotic thrombocytopenic purpura: clinico-pathologic characteristics and
      therapy].
AB  - Thrombotic thrombocytopenic purpura (TTP) is disseminated form of thrombotic
      microangiopathy. Classic clinical presentation is characterized by
      microangiopathic hemolytic anemia, thrombocytopenia, fluctuating neurologic
      symptoms, fever and impaired renal function. In the pathogenesis of TTP important
      role have changes in endothelial cells of small blood vessels, apoptosis,
      elevated endothelial derived proteins, anti-endothelial cell antibodies and
      platelet aggregating factors. In vast majority of patients with TTP deficient
      protease activity for von Willebrand factor (vWF), due to the presence of IgG
      antibodies is reported. Predisposing factors for development of TTP are
      infections, collagen vascular diseases, pregnancy, cancer, drugs, bone marrow
      transplantation, and genetic susceptability to TTP syndrome. Plasma exchange
      transfusions is the standard way of treatment. Additional treatment modalities
      with corticosteroids, cytotoxic drugs, antiplatelet drugs, intravenous
      immunoglobulins and splenectomy are applied.

PMID- 14692152
TI  - [Recommendations for treatment of individuals at risk for hereditary breast and
      ovarian carcinoma].
AB  - Germline mutations in BRCA 1 and BRCA 2 gene have been recognized as hereditary
      predisposition for breast and ovarian cancer for many years. The optimal clinical
      management of individuals at risk for hereditary breast and ovarian cancer are
      not completely defined. Current surveillance options are restricted in their
      effectiveness as well as limitations of the techniques. Surgical prevention
      interventions are effective, but may be complicated by physical and psychological
      morbidity. Genetic testing, which plays a role in defining risk, requires careful
      pre- and post-test counseling to discuss the limitations of testing itself and
      available management strategies.

PMID- 14692153
TI  - [80 years' of internal medicine education at the medical school of the university
      in Belgrade (1922-2002)].
AB  - ORGANISATION OF TEACHING INTERNAL MEDICINE: The Department for Internal Medicine
      and Internal Clinics were founded in spring 1922. Dr. Radenko Stankovic and Dr.
      Dimitrije Antic were appointed as part-time Professors, while Dr. Aleksandar
      Ignjatovski, a former Full-time Professor of the Warsaw University, was appointed
      as professor under contract. A year later, Dr. Aleksandar Radosavljevic was
      appointed as Part-time Professor. In the General State Hospital and Military
      Hospital, certain wards were turned into clinics. II and III Internal Clinics
      were situated in the barracks, while the Propedeutic and I Internal Clinics were
      located in the Military Hospital. Upon the construction of the buildings of the
      Internal Clinic and General State Hospital, the Propedeutic and I Internal
      Clinics were permanently placed in the new building, and II and III Internal
      Clinics in the General State Hospital. Teaching of Internal Medicine started 31
      October 1922. Dr. R. Stanko vic delivered a lecture in Propedeutics for students
      of the fifth term. This date marks the beginning of teaching internal medicine at
      the newly established School of Medicine, University of Belgrade. Dr. A.
      Ignjatovski started lecturing Internal medicine 23 March 1923, whereas Dr. D.
      Antic and and Dr. A. Radosavljevic also delivered lectures in the areas of
      Internal Medicine within their professional scope. At the beginning, the clinics
      belonged to the General State Hospital. It was impossible to teach successfully
      in hospital, therefore upon the professors' request, the clinics were separated
      and thus became the institutions belonging to the School of Medicine-educational
      institutions, while hospitals were health institutions. The rule was 'one
      professor--one clinic'. After the Second World War, teaching Internal Medicine
      was begun in demolished buildings in very difficult financial circumstances. The
      Propedeutic Internal clinic was renamed IV Internal Clinic, which continued
      dealing predominantly with cardiology. III and IV Internal Clinics were placed in
      the building of the Internal Clinic, II Internal Clinic remained in the General
      State Hospital and I Internal clinic was moved to the new building of the
      Institute for Oncology. REFORMS OF SCHOOL OF MEDICINE AND ITS CLINICS: Out of the
      School of Medicine, Veterinary Medicine, Pharmacy and Stomatology, the Grand
      Medical School was formed. After several years, it was closed down, and the
      schools were returned to the University. The most important alteration was made
      when, according to the Law, the Clinics were isolated from the School and
      proclaimed hospitals, health institutions and organised into the Clinical Centre
      of the School of Medicine, then University Clinical Centre, and finally the
      Clinical Centre of Serbia as the teaching base. Within city hospitals, later on
      Clinical Hospital Centres, the teaching bases for Internal Medicine and other
      subjects were established, with introducing self-management and the Law on
      Associated Labour with independent financing, there came hard times for the
      School of  Medicine and Clinics. The Law had negative effects upon the Schools-
      University and it had to be abolished. The next step in the reform was merging of
      I and II Internal Clinics into the Internal B Clinic, within the Clinics, out of
      specialized departments for certain branches of Internal Medicine there were
      formed clinics (Clinic for Cardiology, Pulmonology, Endocrinology, Diabetes and
      Metabolic Diseases and so on). The Internal A Clinic was situated in the building
      of the General State Hospital and the Internal B Clinic in the building of the
      Internal Clinic, where there were also III and IV Internal Clinics. CONSTRUCTION
      OF CLINICAL CENTRE: After a long time, there were created conditions for
      constructing a new building for locating clinics--the Clinical Centre, the
      foundation stone was laid 20 October 1976, and the first phase including the
      polyclinics was completed 1 January 1983. The preliminary concept of the bed
      capacity of 30 to 50 at Internal Clinics was altered and the Institutes were
      established. Firstly, the Internal Clinics was altered and the Institutes were
      established. Firstly, the Internal A and B Clinics were joined into the Basic
      Organisation of Associated Labour Internal Medicine. Afterwards, certain
      specialized Internal Clinics with respective surgical branches were linked and
      the Institutes were established (Institute for Cardiovascular Diseases, Institute
      for Pulmonology and Tuberculosis, Institute for Endocrinology, Diabetes and
      Metabolic Diseases and so on). The Institutes were located at the former
      buildings of the clinics as well as the vacant buildings of the Military Medical
      Academy, which moved into the new modern building at Banjica. Thus, Internal
      Medicine was organisationally closed down, while assistants and professors were
      gathered at the Department for Internal Medicine which represented the
      organisation for teaching Internal Medicine. Professors and assistants from
      certain specialized Institutes taught certain disciplines, and at the Clinical
      Hospital Centre bases where teaching staff was deficient, the Clinical Centre
      professors were of assistance. A colossal Emergency Centre was established within
      the Clinical Centre, providing services for the whole of the Republic and beyond,
      which is completely illogical since it should be the Republic Health Institution
      rather than the part of the Clinical Centre. Also, the Clinical Centre as the
      health institution is enormous and represents the teaching base. The first
      directors were lawyers and, as of recently, professors of the School of Medicine.
      By separating Clinics from the School of Medicine, teaching and allied staff have
      a double working status as unique, so financially more potent health sector has
      gradually pushed aside the teaching one being rather underestimated in such
      organisation. Ministers for Health and Directors of the Clinical Centre great
      executive power for appointing directors. There started an uprecedented
      systematic degradation of teaching staff, since assistant professors or newly
      appointed associated professors were appointed as managers over their own
      teachers, full-time professors. It is unusual that those young people accepted
      their big, delicate roles to manage their professors in front of whom they had
      taken their board exams or defended their masters' and doctoral theses in not so
      distant past. There has only been one case of a junior professor refusing to be
      the director of his own professor. The stationary section of the Clinical Centre
      including the Internal Clinics was completely constructed but has not been
      equipped or occupied yet. Deans were authoriZed, by the University Law, to
      appoint professors and assistants. Thus, a large number of them were appointed
      without any high scientific and teaching quality standards, and afterwards
      promoted, while certain highly competent professors were dismissed from the
      University. By altering the system and passing the new University Law, the
      situation has improved and the University is returning to its roots. Today, such
      Clinical Centre as the teaching base of the School of Medicine and the School
      itself represent a big problem, primarily the financial one. Thus, it will be
      very hard to re-establish the right relationship between these two institutions.

PMID- 14692155
TI  - Critical care nursing in Indonesia.

PMID- 14692154
TI  - Pseudomonas aeruginosa chromosomal beta-lactamase in patients with cystic
      fibrosis and chronic lung infection. Mechanism of antibiotic resistance and
      target of the humoral immune response.
AB  - The intensive antibiotic treatment of cystic fibrosis (CF) patients with chronic
      lung infection with Pseudomonas aeruginosa has improved the survival rate and the
      clinical condition of Danish patients. Acquirement of resistance to anti
      pseudomonal antibiotics is one of the main drawbacks of this therapeutic strategy
      and our results showed the development of resistance of P. aeruginosa to several
      antibiotics during 25 years of intensive antibiotic treatment. Our studies have
      been concentrating on the development of resistance to beta-lactam antibiotics.
      We have shown an association between the development of resistance to beta-lactam
      antibiotics and the occurrence of high beta-lactamase producing strains and
      between the MIC of the beta-lactams and the levels of beta-lactamase expression.
      Partially derepressed mutants, characterized by high basal levels of beta
      lactamase with the possibility of induction to even higher levels during
      treatment with beta-lactam antibiotics, were the most frequent phenotype found
      among resistant Danish P. aeruginosa CF isolates. We have also shown that the
      high alginate producing P. aeruginosa isolates, that characterize the chronic
      lung infection in CF patients, are more susceptible to antibiotics and produce
      less beta-lactamase than the non-mucoid paired isolates. We propose that the non
      mucoid isolates are exposed to a relatively higher antibiotic pressure than the
      mucoid isolates and therefore, they become easily antibiotic resistant and in
      consequence produce high levels of beta-lactamase. The beta-lactamase produced by
      the non-mucoid isolates might play a protective role in the biofilm, defending
      the mucoid isolates from the action of beta-lactam antibiotics and helping them
      to maintain their antibiotic susceptibility. We have also shown that beta
      lactamase, which is a periplasmic enzyme, can be secreted extracellulary packed
      in membrane vesicles liberated by high beta-lactamase-producing P. aeruginosa.
      The continuos presence in the CF lungs of bacteria producing high basal levels of
      beta-lactamase (partial derepressed) induces a humoral immune response to beta
      lactamase. We have shown that antibodies against the chromosomally encoded beta
      lactamase (a beta ab) might be considered a marker of the development of
      resistance to beta-lactam antibiotics. We investigated the humoral immune
      response to beta-lactamase by quantifying a beta ab specific IgG and IgG subclass
      antibodies, by investigating the influence of the allotypes on the IgG subclass
      response and by measuring the avidity of the IgG a beta ab. We found that CF
      patients with good lung function had in the early stages of the chronic lung
      infection higher titers of a beta ab of good avidity than patients with poor lung
      function. Therefore, we raised the hypothesis that some of the a beta ab might
      have beta-lactamase neutralizing effect, playing a beta-lactamase inhibitor role
      and improving the effect of the treatment with beta-lactam antibiotics. Finally,
      we tested our hypothesis in the rat model of chronic lung infection by assessing
      the effect of a beta ab raised by vaccination with purified chromosomal beta
      lactamase on the outcome of the treatment with ceftazidime of bacteria resistant
      to beta-lactam antibiotics. Our results showed that significantly lower bacterial
      load and better lung pathology were found in rats with neutralizing antibodies
      compared to non-immunized rats or rats without neutralizing antibodies. Our
      findings might be of potential importance for the improvement of the treatment
      with beta-lactam antibiotics of resistant P. aeruginosa hyperproducing
      chromosomal beta-lactamase that represent a threat especially for patients with
      CF and chronic lung infection.

PMID- 14692156
TI  - Gaining funding for critical care nursing research.

PMID- 14692157
TI  - Critical care nurses be aware: Lemierre's syndrome is on the rise.
AB  - Lemierre's syndrome (LS) typically occurs in previously healthy young adolescents
      and young adults who become acutely ill following an attack of
      pharyngotonsillitis. Also known as post anginal sepsis, those afflicted develop
      pyrexia, rigours and multiple metastatic abscesses that lead to septic
      thrombophlebitis of the internal jugular vein. In the pre-antibiotic era this
      particularly virulent syndrome had a mortality rate in excess of 90%, but since
      the introduction of antibiotics and the widespread treatment of throat
      infections, it has became almost unknown. However, due to a number of factors,
      including a reduction in the use of antibiotics for the treatment of sore
      throats, misdiagnosis and/or improvements in microbiology diagnostic techniques,
      several reports have indicated a resurgence of the condition. This has major
      ramifications for critical care nurses as LS is still associated with significant
      morbidity and mortality. This paper discusses the aetiology, pathophysiology,
      bacteriology, diagnosis and management aspects of this syndrome. A case study of
      a young woman is presented to illustrate the complexity of the condition, and
      highlight how early diagnosis and prompt initiation of appropriate intravenous
      antibiotic therapy ensured a favourable clinical outcome.

PMID- 14692158
TI  - The use of activated protein C (drotrecogin alfa (activated)) in the treatment of
      severe sepsis.
AB  - Advances in intensive care have allowed many critically ill patients to survive
      their initial insult. These patients may later demonstrate multiple organ
      dysfunction and failure, the genesis of which appears to be the body's reaction
      to critical illness, manifested by an imbalance and failure of inflammatory and
      immune system homeostasis. The manifestation of multiple organ dysfunction in the
      critically ill has been termed multiple organ dysfunction syndrome (MODS). MODS
      mortality is high and remains a leading cause of death in intensive care units
      (ICUs). The understanding of the pathophysiology of severe sepsis and MODS has
      moved from a focus on inflammation to include an understanding of the associated
      anti-inflammatory responses. Loss of homeostasis can manifest as malignant
      inflammation or immune paralysis. Increased emphasis is emerging on the role of
      loss of immune homeostasis and disordered coagulation as a cause of organ injury
      and dysfunction. Treatment of severe sepsis is based upon aggressive
      resuscitation, source control and support for failing organs. Novel therapies
      directed at the modifying the inflammatory response have, up to now, not proven
      beneficial. However, a new agent, drotrecogin alfa (activated) has been shown, in
      a phase III randomised controlled trial, to be of benefit in the treatment of
      severe sepsis. This new agent affects both the inflammatory and coagulation
      dimensions of severe sepsis. The developing concepts of the pathophysiology of
      sepsis and the emergence of a new therapy increases the complexity of the already
      complex demands of providing nursing care for the patient with severe sepsis and
      MODS. This article reviews pathophysiological processes in sepsis, reviews
      clinical data on activated protein C and illustrates the utility of this therapy
      in a case study.

PMID- 14692159
TI  - Torsades de pointes following cardioversion: case history and literature review.
AB  - Torsades de pointes (TDP) is a relatively uncommon but potentially fatal cardiac
      arrhythmia which occurs in patients with long QT syndromes (LQTS). This
      literature review and case history investigate the causes, symptoms, presentation
      and treatment of torsades, focusing on drug induced torsades developing after
      successful cardioversion. In torsades, imbalanced positive ion flows result in
      early after-depolarisations (EADs) and increased variability in repolarisation
      rates. These combine to create an unstable re-entrant polymorphic ventricular
      tachycardia (VT) which can cause patients to suffer symptoms progressing from
      syncope to ventricular fibrillation (VF) arrest. Typically, torsades has a
      twisting morphological presentation on rhythm strips due to the irregularity of
      its re-entry pattern. The arrhythmia is more common in women. Intravenous
      magnesium is the initial emergency treatment in torsades. The case history
      illustrates the progressive acquisition of risk factors for drug induced torsades
      in a patient treated with sotalol following cardioversion. Typical progressive
      rhythm strip, electrocardiograph (ECG), and QT & corrected QT interval (QTc)
      interval changes occurring with the arrhythmia are presented.

PMID- 14692160
TI  - Granny sucks snakebite: a study of an envenomation.
AB  - This paper examines the management of a young patient who was admitted to
      hospital following a suspected envenomation by a common death adder (Acanthopis
      antarticus) whilst holidaying at his grandmother's house. It describes the
      progress of the patient from the First Aid he received at home through to
      discharge, including medical and nursing management whilst in the emergency
      department and the intensive care unit (ICU). The paper also describes some of
      the common elements related to snake envenomation such as the clinical
      manifestations that suggest envenomation as well as the diagnosis and management
      of the envenomed patient.

PMID- 14692161
TI  - Five more ways to add $200,000 or more to your practice.

PMID- 14692162
TI  - Restoring anterior maxillary dentition using alumina- and zirconia-based CAD/CAM
      restorations.
AB  - Despite proven strength, durability, and improved esthetics, ceramometal
      restorations have not consistently enabled the most esthetic, lifelike
      reproduction of natural dentition. Also, inherent weaknesses in many metal-free
      materials have precluded their use in the high stress-bearing posterior region.
      Therefore, as a result of the need for esthetic and durable all-ceramic
      restorations, manufacturers have introduced ceramics with an increased alumina or
      zirconia content that are recommended for placement anywhere in the mouth for
      single units and as far back as the first premolar.

PMID- 14692163
TI  - Direct placement alternatives for anterior, esthetic rehabilitation.

PMID- 14692165
TI  - New technology directions in resin cements.

PMID- 14692164
TI  - CAD/CAM ceramic restorations in the operatory and laboratory.
AB  - Computer assisted design/computer assisted machining (CAD/CAM) technology has
      received considerable clinical and research interest from modern dental practices
      as a means of delivering all-ceramic restorations. The CEREC, System offers
      CAD/CAM dental technology designed for clinical use by dentists, as well as a
      separate system designed for dental laboratory technicians. The CEREC 3 system is
      indicated for dental operatory applications, and the CEREC inLab, system is
      indicated for dental laboratory applications. Although both systems rely on
      similar CAD/CAM technology, several significant differences exist in the
      processing techniques involved, restorative materials used, and types of
      restoration provided.

PMID- 14692166
TI  - A clinical investigation of the efficacy of a tooth-whitening gel.
AB  - The objective of this randomized, controlled, examiner-blind, parallel-group
      clinical study was to determine whether a tooth-whitening gel (Colgate Simply
      White Night Clear Whitening Gel) can significantly lighten teeth when used once
      daily at night, as compared with a commercially available dentifrice. Following a
      baseline tooth shade evaluation using the VITA Shade Guide, qualifying adult male
      and female subjects from the Buffalo, New York area were randomized into 2
      treatment groups, which were balanced for baseline VITA Shade Guide scores,
      gender, and age. The treatment groups were: (1) a commercially available
      dentifrice only; and (2) a tooth-whitening gel in addition to a commercially
      available dentifrice. Subjects assigned to the 2 groups were given the dentifrice
      and a soft-bristled toothbrush. In addition, subjects in one of the groups were
      given the tooth-whitening gel. All subjects were instructed to brush their teeth
      for 1 minute twice daily (morning and evening) with the dentifrice. The subjects
      in the group also using the tooth-whitening gel were further instructed to apply
      the gel once daily at night, as per manufacturer instructions. Evaluations of
      tooth shade for each subject were repeated after 2 weeks, and again after 3 weeks
      of product use. In addition, evaluations of tooth shade for subjects using the
      tooth-whitening gel were later conducted at 6 months after product use. Seventy
      five subjects complied with the protocol and completed the study. At the 2-week
      and 3-week examinations, subjects using the tooth-whitening gel and dentifrice
      exhibited statistically significant (P < .05) tooth shade lightening relative to
      baseline tooth shade. Furthermore, at the 2-week and 3-week examinations,
      subjects using the tooth-whitening gel exhibited statistically significant (P <
      .05) tooth shade lightening relative to subjects using only the dentifrice. In
      addition, the 6-month-postuse examination showed that subjects using the tooth
      whitening gel exhibited statistically significant (P < .05) tooth shade
      lightening relative to baseline, thereby maintaining the tooth shade lightening
      that was evident at 3 weeks. The results of this clinical study indicate that
      after once-daily use at night for 2 or 3 weeks, the tooth-whitening gel provided
      statistically significant tooth shade lightening relative to baseline tooth shade
      for up to at least 6 months and also provided statistically significant tooth
      shade lightening relative to a commercially available dentifrice after 2 and 3
      weeks of product use.

PMID- 14692167
TI  - Crown lengthening for optimum restorative success.

PMID- 14692168
TI  - Modified technique for stage 1 indexing using the XiVE system.

PMID- 14692169
TI  - Rhabdomyolysis. Pathophysiology, recognition, and management.
AB  - Rhabdomyolysis is a clinical syndrome in which the contents of injured muscle
      cells leak into the circulation. This leakage results in electrolyte
      abnormalities, acidosis, clotting disorders, hypovolemia, and acute renal
      failure. More than 100 conditions, both traumatic and non-traumatic, can lead to
      rhabdomyolysis. Intervention consists of early detection, treatment of the
      underlying cause, volume replacement, urinary alkalinization, and aggressive
      diuresis or hemodialysis. Patients with rhabdomyolysis often require intensive
      care, and critical care nurses are instrumental in both the early detection and
      the ongoing management of this life-threatening syndrome.

PMID- 14692170
TI  - Blood management strategies for critical care patients.

PMID- 14692171
TI  - Anaphylactoid syndrome of pregnancy. A devastating complication requiring
      intensive care.

PMID- 14692172
TI  - Nutrition support in the intensive care unit. Adequacy, timeliness, and outcomes.

PMID- 14692173
TI  - Argatroban, a new treatment option for heparin-induced thrombocytopenia.

PMID- 14692174
TI  - An MSN curriculum in preparation of CCNSs: a model for consideration.

PMID- 14692175
TI  - The first element of negligence.

PMID- 14692176
TI  - Contextualizing immigrants' lived experience: story of Taiwanese immigrants in
      the United States.
AB  - Immigration involves extensive changes in living environments. Nonetheless, the
      predominant approach in the health science literature has been to utilize
      individual characteristics (including ethnic background) to explain and predict
      immigrants' lived experiences and health outcomes. Contexts, particularly the
      larger societal contexts by which immigrants are constituted, are generally
      ignored. Data from a critical ethnography regarding immigrants' experiences with
      language, occupation, and economic survival in the United States are utilized to
      illustrate that immigrants' lives are inseparable from the larger societal
      contexts, such as immigration policy, Western imperialism, and structural
      discrimination. The implications for practice, education, and research are
      discussed.

PMID- 14692177
TI  - A descriptive analysis of CRRIC II results: cardiovascular risks of African
      American children in Mississippi.
AB  - The burgeoning problem of overweight and obesity in US children, adolescents, and
      adults has reached epidemic proportions. Data from the CRRIC I study conducted in
      2000 in Jackson, Mississippi among elementary African-American children indicated
      that 39% of the boys and 49% of the girls had BMIs at or above the 85th
      percentile. The current study replicated CRRIC I in a sample of 113 African
      American Children in the third and fourth grades in the rural town of Canton,
      Mississippi. Results revealed that 46% of the boys and 46% of the girls had BMI
      at or above the 85th percentile. Fitness profile results revealed that only 11%
      of the children were classified as fit, 84% were classified as fair, and 5% were
      deemed unfit. As in CRRIC I, health histories of grandparents were positive for
      the comorbities of overweight and obesity: diabetes, stroke, and heart disease.
      These data indicate a critical need to aggressively intervene to impact the
      lifestyle choices of this generation.

PMID- 14692178
TI  - Educating nurses in Rhode Island: a lot of diversity in a little place.
AB  - Faculty at a baccalaureate nursing program at a state college discuss a
      multifaceted approach to meeting the needs of a very diverse student population.
      These students reflect the changing demographics of the state and their education
      contributes to providing a racially, ethnically, and culturally diverse nursing
      workforce. The program addresses multiple issues which may impede academic
      performance. These measures have enhanced and promoted graduates' success on
      NCLEX-RN. Creative and varied strategies are presented and their implementation
      and evaluation described.

PMID- 14692179
TI  - Partner violence, depression, and practice implications with families of Chinese
      descent.
AB  - Because the Chinese tend to display psychological problems such as depression in
      somatic This article examines cultural aspects, experiences, and the mental
      health consequences of partner violence among families of Chinese descent. A
      total of 262 Chinese men and women participated in a telephone survey about
      partner violence and psychological well-being. Symptoms, two indicators of mental
      health were employed in the research study. Findings indicated a high level of
      verbal aggression both perpetrated and sustained by participants. Rates of
      physical abuse were lower; however, these figures dispel the model minority myth
      associated with Asian Americans. In addition, findings showed a positive
      correlation between depression and partner violence. Those who experienced verbal
      and physical aggression by a spouse/intimate partner in the last 12 months were
      more likely to experience depression. Those who perpetrated physical aggression
      were more likely to experience somatic symptoms. Practice and research
      implications are highlighted.

PMID- 14692180
TI  - Patient safety: maintaining the momentum.

PMID- 14692181
TI  - Meeting the challenge of managing vaso-occlusive crisis.
AB  - Quality improvement efforts in patient care are most successful when the entire
      healthcare team is involved in care planning. This article discusses a
      multidisciplinary approach to the development of a protocol for patients with
      sickle cell disease experiencing vaso-occlusive crisis. The protocol's goal was
      to improve the quality and consistency of care for these patients. Outcomes,
      which were based on data from the 6 months before and after the protocol
      initiation, demonstrated an increased treat-and-release rate from the emergency
      department, a decreased average length of stay, and a decrease in the percentage
      of patient days down-graded by payers.

PMID- 14692182
TI  - Changing attitudes among nurses and physicians: a step toward collaboration.
AB  - Nurse-physician collaboration is a major contributing factor in positive patient
      outcomes. A first step toward collaboration is an understanding of, and respect
      for, one another's roles. As part of a quality improvement project, we
      implemented a curriculum in which medical students "shadowed" nurses for 1 day
      and then measured the impact on their attitudes toward nurses' roles. Sixty-five
      students completed the program. Thirty students completed a validated survey
      instrument before and after the experience. Students demonstrated a trend toward
      improvement on the attitudes survey. Medical students highly valued the program
      and better appreciated nurses' roles.

PMID- 14692183
TI  - Lucian Leape and healthcare errors. Interview by Pamela K. Scarrow and Susan V.
      White.
AB  - Lucian L. Leape, MD, is a health policy analyst whose research has focused on
      error prevention and appropriateness of care. He is currently adjunct professor
      of health policy at the Harvard School of Public Health. Prior to joining the
      faculty at Harvard, he was professor of surgery at Tufts University School of
      Medicine and chief of pediatric surgery at the New England Medical Center. He has
      been a leading advocate of the nonpunitive systems approach to the prevention of
      medical error and has led several studies of adverse drug events and their
      underlying systems failures. In addition, he has directed research into overuse
      and underuse of cardiovascular procedures. Dr. Leape was a founding director of
      the National Patient Safety Foundation, the Massachusetts Coalition for the
      Prevention of Medical Error, and the Harvard Kennedy School Executive Session. He
      led the Institute for Healthcare Improvement's first Breakthrough Collaborative
      on Prevention of Adverse Drug Events. He was a member of the Institute of
      Medicine (IOM) Quality of Health Care in America Committee, which recently
      released its reports, To Err Is Human: Building a Safer Health System and
      Crossing the Quality Chasm: A New Health System for the 21st Century. Recent
      awards include the Distinguished Service Award of the American Pediatric Surgical
      Association (1997), the Robert Wood Johnson Investigator Award (1998), the
      Donabedian Award from the Medical Care Section of the American Public Health
      Association (1999), the Cheers Award from the Institute for Safe Medication
      Practices (1999), and the Pinnacle Award from the American Pharmaceutical
      Association (2001). Dr. Leape is a graduate of Cornell University and Harvard
      Medical School and trained in surgery at Massachusetts General Hospital and at
      Boston Children's Hospital.

PMID- 14692184
TI  - Forty hours under pressure: a rapid-response improvement team achieves synergy.
AB  - A rapid-response team process was used to achieve unique team synergy and project
      success. The team's mission was to reduce the waiting time in the emergency care
      unit for inpatient telemetry beds. Data needed for root cause analysis were
      collected before the first team meeting, and "just-in-time" team training was
      provided at the team's first meeting. With leadership from the chief executive
      officer, a vice president, and a core group of physicians, the team was energized
      to complete the mission and present its plan to the entire executive team at the
      end of just 1 week.

PMID- 14692186
TI  - Tips for teaching quality concepts to international audiences.
AB  - Healthcare quality professionals in the United States have opportunities to teach
      healthcare providers in other countries how to measure and monitor quality.
      Special preparation is required to effectively teach an international audience.
      This article offers tips for teaching basic quality concepts based upon the
      authors' experiences in the People's Republic of China. Working with health
      professionals in other countries is exciting and challenging for everyone
      involved. Approaching the opportunity with systematic preparation may be the key
      to success.

PMID- 14692185
TI  - A framework for selecting performance measures for opioid treatment programs.
AB  - As a result of new federal regulations released in early 2001 that move the
      monitoring and evaluation of opioid treatment programs from a government
      regulation to an accreditation model, program staff members are now being
      challenged to develop performance measurement systems that improve care and
      service. Using measurement selection criteria is the first step in developing a
      performance measurement system as a component of an overall quality management
      (QM) strategy. Opioid treatment programs can "leapfrog" the development of such
      systems by using lessons learned from the healthcare quality industry. This
      article reviews performance measurement definitions, proposes performance
      measurement selection criteria, and makes a business case for Internet automation
      and accessibility. Performance measurement sets that are appropriate for opioid
      treatment programs are proposed, followed by a discussion on how performance
      measurement can be used within a comprehensive QM program. It is hoped that
      through development, adoption, and implementation of such a performance
      measurement program, treatment for clients and their families will continuously
      improve.

PMID- 14692187
TI  - Peutz-Jeghers polyposis with enteritis cystica profunda--a diagnostic pitfall.

PMID- 14692188
TI  - Retroperitoneal neurofibrosarcoma in a patient with neurofibromatosis. 2: A case
      report and review of the literature.
AB  - Neurofibromatosis (NF) type I (NF1) is the most common familial cancer
      predisposing syndrome in humans, while type 2 (NF2) accounts for an extremely
      small percentage of the total cases of NF. Tumors occurring in patients with NF1
      are primarily peripheral neurofibromas, while NF2 patients present with central
      schwannomas. Malignant transformation has been described in NF1 patients;
      however, in NF2 the risk of malignant transformation is extremely rare. In this
      case report, the authors document a retroperitoneal neurogenic sarcoma occurring
      in a 20-year-old woman with NF2 (bilateral acoustic schwannomas, meningioma, and
      multiple intraspinal tumors).

PMID- 14692189
TI  - The confused identity of Cantrell's pentad: ectopia cordis is related either to
      thoracoschisis or to a diaphragmatic hernia with an omphalocele.
AB  - To find out if Cantrell's pentad is a single entity, four cases of ectopia cordis
      were studied and compared with cases in the literature. Our cases had the heart
      outside the thorax and had two to four other features of the association. In one
      case the thoracic organs had apparently escaped through a diaphragmatic hernia
      into an omphalocele, and in the others via a thoracoschisis with an abdominal
      defect, either a supraumbilical hernia or a gastroschisis. According to these
      cases and those from the literature, it is proposed that there are two major
      mechanisms leading to ectopia cordis: (1) a reversed diaphragmatic hernia in the
      case of a large diaphragmatic defect and an omphalocele, and (2) through a sterno
      costal defect, with gastroschisis or a supraumbililical abdominal defect. As
      omphaloceles and major diaphragmatic defects are probably pathogenetically
      distinct from thoraco- and thoracogastroschisis, it is important to distinguish
      these groups of anomalies, rather than be concerned as to their relationship with
      Cantrell's pentad.

PMID- 14692190
TI  - Rectal primitive neuroectodermal tumor.
AB  - We report the clinical, histologic, immunohistochemical, and molecular findings
      of a Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) localized to the
      rectum in a 17-year-old boy. Notably the 4.5 x 4 x 4-cm sessile mass was
      spontaneously eliminated through the anus, producing an episode of hemorrhagic
      shock. Histologically the tumor presented as a proliferation of membrane CD99
      positive, small round cells. EWS/FLI1 chimeric mRNA was demonstrated by nested
      reverse-transcription polymerase chain reaction (RT-PCR) analysis in the tumor
      tissue. The patient is alive and well 2 years after initial symptoms. We also
      review reported cases of ES/PNET of the digestive system.

PMID- 14692191
TI  - Congenital Rosai-Dorfman disease without lymphadenopathy.
AB  - Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder with
      massive lymphadenopathy. We here describe RDD of a neonate who presented with
      paleness and hepatosplenomegaly but not lymph-node swelling. Routine laboratory
      studies showed anemia, thrombocytopenia, and an elevated value of gamma-glutamyl
      transpeptidase. Histological examination of the liver revealed a proliferation of
      histiocytes with abundant eosinophilic cytoplasm, which were positive for S-100
      protein and CD68 but not CD1a and did not reveal Birbeck granules. Radiological
      studies showed hepatosplenomegaly and a narrowing of the hepatic vein, which
      might have contributed to hypersplenism resulting in anemia and thrombocytopenia.
      This case is thought to be congenital RDD without lymphadenopathy.

PMID- 14692192
TI  - Nonfunctioning adrenocortical carcinoma in a child.
AB  - Pediatric nonfunctioning adrenocortical carcinoma is a very rare tumor. A 4-year
      old girl was admitted complaining of abdominal pain. Physical examination
      revealed an abdominal mass. There were no clinical or laboratory signs of
      hormonal abnormality. Abdominal ultrasonography revealed a polylobular mass.
      Intravenous pyelography showed marked compression of the kidney by a tumor. The
      tumor was excised together with the right kidney. The histopathological diagnosis
      was adrenocortical carcinoma. Although there is a greater incidence of germ line
      p53 mutations with adrenocortical carcinoma, the tumor suppressor gene p53 was
      not mutated in our case. The girl died 2 months after surgery from complications
      of chemotherapy.

PMID- 14692193
TI  - Hypothalamic digoxin-mediated model for trisomy 21.
AB  - The isoprenoid pathway related cascade was assessed in trisomy 21. Membrane Na+,
      K(+)-ATPase activity, serum magnesium, and ubiquinone were decreased while
      hydroxy methyl glutaryl CoA (HMG) coenzyme A (CoA) reductase activity, serum
      digoxin, and dolichol levels were increased in trisomy 21. There were increased
      levels of tryptophan catabolites--nicotine, strychnine, quinolinic acid, and
      serotonin--and decreased levels of tyrosine catabolites--dopamine, noradrenaline,
      and morphine in trisomy 21. There was an increase in dolichol levels,
      carbohydrate residues of glycoproteins, glycolipids, total/individual
      glycosaminoglycan (GAG) fractions, and lysosomal enzymes in trisomy 21. Reduced
      levels of ubiquinone, reduced glutathione, and free radical scavenging enzymes as
      well as increased lipid peroxidation products and nitric oxide were noticed in
      trisomy 21. Hypothalamic digoxin and a disordered isoprenoid pathway are
      important in the pathogenesis of trisomy 21.

PMID- 14692194
TI  - The isoprenoid pathway and the pathogenesis of Reye's syndrome.
AB  - The isoprenoid pathway produces three key metabolites: endogenous digoxin
      (regulator of neurotransmitter uptake), dolichol, and ubiquinone (free radical
      scavenger). Since a mitochondrial dysfunction has been described in Reye's
      syndrome, it was considered pertinent to assess the pathway in this disease.
      Since endogenous digoxin can regulate neurotransmitter transport, the pathway was
      also assessed in patients with right hemispheric, left hemispheric, and
      bihemispheric dominance to find out the role of hemispheric dominance in its
      pathogenesis. The plasma/serum activity of hydroxy methyl glutaryl (HMG) coenzyme
      A (CoA) reductase, magnesium, digoxin, dolichol, ubiquinone, tryptophan/tyrosine
      catabolic patterns, and free radical and lipid levels, as well as RBC Na+, K(+)
      ATPase activity, were measured in the groups mentioned. RESULTS: In the patient
      group as well as in individuals with right hemispheric dominance similar patterns
      were obtained. There was elevated digoxin and dolichol levels with low levels of
      ubiquinone in patients with Reye's syndrome as well as in those with right
      hemispheric dominance. The serum magnesium and RBC Na+, K(+)-ATPase activity were
      reduced. There was also an increase in tryptophan catabolites and a reduction in
      tyrosine catabolites as well as increased free radical levels. Reye's syndrome is
      associated with an upregulated isoprenoid pathway, elevated hypothalamic digoxin
      secretion, and right hemispheric chemical dominance.

PMID- 14692195
TI  - An unusual renal malignancy of childhood: unilateral teratoid Wilms's tumor.
AB  - Teratoid Wilms's tumor is a rare histologic variant of the classical Wilms's
      tumor, containing predominantly heterolougus tissues (adipose, glial, muscle,
      cartilage, or bone). We report an unusual variant of such tumor, which simulated
      renal teratoma because of abundant fat within the tumor. The child underwent
      radical excision; postoperatively, he was treated with chemotherapy, and now the
      child is well at 36 months after surgery. The behavior of this kind of tumor
      usually is not aggressive, and the outcome is good. Surgery should be the
      treatment of choice, because the efficacy of chemotherapy and radiotherapy is
      probably reduced by the high amount of differentiated and mature tissue that
      characterizes this neoplasm. Radiologic imaging and pathological features of this
      rare entity are described.

PMID- 14692196
TI  - Pathology teach and tell: central nervous system atypical teratoid/rhabdoid
      tumor.
AB  - Atypical teratoid/rhabdoid tumor (AT/RT) is extremely malignant, highly
      aggressive primitive central nervous systemneoplasm of infancy with very poor
      prognosis. Histologically, AT/RT is defined as a polymorphous neoplasm often
      featuring rhabdoid, PNET, mesenchymal, and epithelial components. We report the
      clinical history, radiological, and pathological findings in a child affected
      bycentral nervous system AT/RT.

PMID- 14692197
TI  - The changing faces of diabetes.
AB  - As understanding about the pathophysiology of diabetes mellitus continues to
      evolve, it is important that its classification reflects the current state of
      knowledge. The eventual goal is that appreciation of the different forms of
      diabetes eventually will result in better treatment of hyperglycemia. Even more
      exciting is the fact that this appreciation is allowing us to enter the era of
      diabetes prediction and prevention. The current classification scheme of diabetes
      does not yet account for all of the types of diabetes seen in a typical diabetes
      clinic. Fig. 1 illustrates our current understanding of the pathophysiology of
      diabetes and separates the diabetes types into those used in the current
      classification scheme. Clearly, new classifications will be required as we learn
      more about the different types of diabetes.

PMID- 14692198
TI  - Prevention of type 2 diabetes: data from recent trials.
AB  - All four main studies of lifestyle intervention on diabetes incidence found a
      clear benefit for diet and exercise intervention compared with usual care.
      Although the study populations differed by race and ethnicity, the mean BMI, and
      the intensity of the lifestyle intervention provided, all investigators found
      substantial diabetes risk reduction with modest weight loss and increased
      physical activity. Results of these trials give health care providers useful and
      heartening information to share with patients at risk for diabetes. The challenge
      remains to find feasible and cost-efficient methods to identify people at risk
      and to deliver effective lifestyle interventions. Findings from trials of
      pharmacologic agents such as metformin, acarbose, and troglitazone are
      encouraging; however, the ADA recommends that drug therapy should not be used
      routinely to prevent diabetes until more information regarding the cost
      effectiveness of such intervention is known [20]. Results from trials that found
      a lower incidence of diabetes among those randomly assigned to angiotensin
      converting enzyme inhibitors, statins, or hormone therapy are intriguing but must
      be viewed with caution because they are based on post hoc analyses. Because it is
      difficult to conduct randomized controlled trials of major operative procedures
      such as bariatric surgery, observational studies that compare surgical
      interventions for weight loss with traditional weight-loss management may be the
      best evidence available. These studies have the potential for healthy-person bias
      in that people who choose bariatric surgery may have other healthy behaviors that
      are often difficult to measure and control for; such behaviors could account for
      their lower incidence of diabetes. Undeniably, the best test to diagnose those at
      high risk for diabetes is not yet known. New strategies that identify those with
      pre-diabetes and that overcome the limitations of the current tests, particularly
      the 2-hour post-challenge glucose test, are needed.

PMID- 14692199
TI  - Treating diabetes using oral agents.
AB  - Since the development and release of sulfonylureas for the treatment of T2DM,
      additional oral glycemic control agents with different mechanisms of action have
      allowed for more flexibility in targeting drug to patient. Based on available
      evidence, metformin monotherapy is preferred for the vast majority of T2DM
      patients who are overweight or obese. Combination therapy has further improved
      glycemic control. However, limitations in use, including the challenges of side
      effects, to that of secondary oral agent failure will inevitably occur over time.
      These challenges leave ample room for the development of agents that address the
      pathophysiology not only of treating insulin resistance and decreasing insulin
      production but also of preventing or delaying the development of diabetes in
      populations at risk.

PMID- 14692200
TI  - Common problems in outpatient management of patients with diabetes in the age of
      insulin analogues.
AB  - Most patients with diabetes are managed in an outpatient primary care setting.
      This article reviews common dilemmas in outpatient insulin therapy and presents
      the evidence regarding the rational use of insulin therapy and combination oral
      agent-insulin therapy.

PMID- 14692201
TI  - Inpatient management of diabetes.
AB  - Hyperglycemia is common in hospitalized patients with diabetes and contributes to
      poor outcomes in this population. Use of intravenous insulin protocols for
      patients who are unable to eat, continuation of usual insulin regimens for those
      who are eating, pre-meal insulin supplements for hyperglycemia, and avoidance of
      sliding-scale insulin can help the clinician improve glycemic control. Careful
      attention to management of diabetes in the hospitalized patient decreases the
      risk of ketoacidosis, fluid and electrolyte abnormalities, and infection; in
      critically ill postoperative patients, tight glucose control with insulin
      administration decreases the risk of death.

PMID- 14692202
TI  - Preventing cardiovascular disease in diabetes and glucose intolerance: evidence
      and implications for care.
AB  - With the increased attention being given to cardiovascular risk factor reduction,
      the opportunity exists to substantially decrease the largest cause of mortality
      in diabetic patients. The concept that type 2 diabetes and CVD are linked via a
      common etiologic pathway (metabolic syndrome) has substantial ramifications for
      the care of individual patients. Many of the metabolic abnormalities that
      contribute to both glycemic disorders and CVD are interrelated. For example,
      hyperinsulinemia and insulin resistance coupled with abdominal obesity further
      worsens HTN and hyperlipidemia. Likewise, the procoagulant state and endothelial
      dysfunction increase with worsening glycemic control. Specific interventions
      include tobacco cessation, a food management and physical activity plan, choice
      of antidiabetic agent (such as metformin), and use of ACE inhibitors for
      hypertension and microalbuminuria (Table 5). Programs to enhance cardiovascular
      risk factor reduction as part of the comprehensive evaluation and management of
      diabetic patients have been described [95,99]. One community-based program
      provided free screening to diabetic patients with randomization to either
      annotated result reports provided to the patient and their physician or results
      provided by a project nurse (either face-to-face or over the phone). Greater
      improvements in mean glycohemoglobin, cholesterol, and blood pressure were noted
      with verbal presentation of results [99]. Recent data from the Centers for
      Disease Control and Prevention Diabetes Cost-effectiveness Group support the idea
      that interventions to decrease CVD in diabetics are economically beneficial.
      Intensive management of hypertension, glycemic control, and hyperlipidemia each
      improved health outcomes. Hypertension control reduced costs. Although intensive
      treatment of glucose and hyperlipidemia increased costs, the increase was
      comparable to that of other frequently used health care interventions [100].
      Further directions include further exploration of the implications and management
      of metabolic syndrome as it relates to CVD prevention. Interventions such as
      exercise, which can impact on all outcomes, require special attention. Efforts by
      physicians, health systems, and society are necessary to increase physical
      activity for individuals of all ages. It makes clinical sense that the
      recommendations for prevention of CVD in diabetics described in this article may
      also benefit patients with prediabetes (fasting glucose 110-125 mg/dl), but this
      remains to be definitively shown.

PMID- 14692203
TI  - Management of patients on chronic glucocorticoid therapy: an endocrine
      perspective.
AB  - Glucocorticoids continue to be a potent therapeutic tool for various medical
      conditions; however, their medication side effects pose challenges. Steroid
      diabetes is treated primarily with prandial insulin, either regular or the rapid
      insulins (lispro or aspart). Intermediate insulin is indicated less frequently,
      for fasting hyperglycemia. Osteoporosis is the most debilitating of potential
      glucocorticoid side effects, with bisphosphonates the mainstay of prevention and
      treatment. Dyslipidemia can range from mild to significant, but it responds to
      therapy similar to that of nonglucocorticoid-induced lipid disorders.
      Glucocorticoid-induced adrenal withdrawal syndrome can occur even with short
      courses of longer-acting glucocorticoid therapy, but it responds to adjustment of
      glucocorticoid dose. When tapering down to near-physiologic dose, pituitary
      adrenal axis responsiveness should be checked before discontinuing steroid use.

PMID- 14692204
TI  - Medical myths involving diabetes.
AB  - Medical myths occur for many different reasons. Myths surrounding diabetes are
      common and are usually attributable to practices that have not been evaluated
      rigorously (sliding-scale insulin use), concerns related to pathophysiology (beta
      blocker use), or extrapolation from small studies or case series (niacin use in
      patients with diabetes). Myths often are passed on from generation of house staff
      to students by word of mouth. It is often difficult to determine the origins of
      some myths, as is the case with sliding-scale insulin use. Other myths may have
      grown from the inclusion of information from a small case series in an
      authoritative text [1]. Understanding the myths and misconceptions about the care
      of patients with diabetes is important in providing excellent care to the patient
      with diabetes.

PMID- 14692205
TI  - The technology behind Colgate Total Advanced Fresh.
AB  - In the early 1990s, a breakthrough toothpaste, Colgate Total, was launched with
      documented long-lasting activity against plaque, gingivitis, calculus, tooth
      decay, and bad breath. The technology behind this toothpaste is the combination
      of triclosan, a polyvinylmethylether/maleic acid copolymer, and sodium fluoride.
      The copolymer ensures maximal oral retention and subsequent release of the
      antibacterial triclosan. Effective levels of triclosan have been observed in the
      oral cavity 12 hours after brushing the teeth, allowing prolonged control of oral
      bacteria that may cause the most common dental problems, including bad breath.
      Similarly, the enhanced retention of triclosan to oral surfaces after using this
      revolutionary toothpaste for up to 2 years has led to significantly reduced
      incremental coronal caries compared to an American Dental Association-Approved
      anticavity fluoride toothpaste. Furthermore, significantly less calcium remained
      in dental plaque after brushing the teeth with the triclosan/copolymer
      toothpaste, resulting in the formation of less tartar. In keeping with the
      multiple oral health benefits provided by Colgate Total, consumers are now
      offered a new dentifrice, Colgate Total Advanced Fresh, which provides the
      numerous therapeutic and esthetic benefits that are the hallmark of Colgate
      Total. The new dentifrice, which contains an impactful breath-freshening flavor,
      has been documented to provide sustained control of bad breath over 12 hours.

PMID- 14692206
TI  - In vitro efficacy of Colgate Total advanced fresh.
AB  - Generally, clinical studies using organoleptic judges, gas chromatography, or a
      sulfide monitor have been employed in the assessment of treatments for the
      control of oral malodor. However, these studies can be expensive and time
      consuming. Also, for agents whose safety has not been proven, these methods are
      not appropriate. Therefore, in vitro assessment is a critical step toward
      developing a new technology or implementing changes to an existing formula. The
      in vitro methods employed in this study combined basic microbiology methods, such
      as growth inhibition and zone of inhibition experiments. In addition, a newly
      developed, in vitro, volatile sulfur compounds (VSC) experiment that combined the
      essential elements of zone of inhibition, head space analysis, and dynamic flow
      cell techniques was also employed. The in vitro VSC method has been validated
      using technologies clinically proven to control oral malodor. All in vitro
      experiments have demonstrated that Colgate Total Advanced Fresh toothpaste has
      efficacy similar to that of the original Colgate Total toothpaste and that both
      variants showed superior efficacy to the control toothpaste. These results have
      been corroborated by clinical study results.

PMID- 14692207
TI  - The effects of a new therapeutic triclosan/copolymer/sodium-fluoride dentifrice
      on oral bacteria, including odorigenic species.
AB  - This investigation examined the in vitro and ex vivo antimicrobial effects of a
      new dentifrice, Colgate Total Advanced Fresh, formulated with
      triclosan/copolymer/sodium fluoride, on oral bacteria, including those odorigenic
      bacteria implicated in bad breath. The effects of Colgate Total Advanced Fresh
      were compared to commercially available fluoride dentifrices that served as
      controls. Three experimental approaches were undertaken for these studies. In the
      first approach, the dentifrice formulations were tested in vitro against 13
      species of oral bacteria implicated in bad breath. The second approach examined
      the antimicrobial activity derived from dentifrice that was adsorbed to and
      released from hydroxyapatite disks. In this approach, dentifrice-treated
      hydroxyapatite disks were immersed in a suspension of bacteria, and reduction in
      bacterial viability from the release of bioactive agents from hydroxyapatite was
      determined. The third approach examined the effect of treating bacteria
      immediately after their removal from the oral cavity of 11 adult human
      volunteers. This ex vivo study examined the viability of cultivable oral bacteria
      after dentifrice treatment for 2 minutes. Antimicrobial effects were determined
      by plating Colgate Total Advanced Fresh and control-dentifrice-treated samples on
      enriched media (for all cultivable oral bacteria) and indicator media (for
      hydrogen-sulfide-producing organisms), respectively. Results indicated that the
      antimicrobial effects of Colgate Total Advanced Fresh were significantly greater
      than either of the other dentifrices for all 13 oral odorigenic bacterial strains
      tested in vitro (P < or = 0.05). In the second approach, Colgate Total Advanced
      Fresh-treated hydroxyapatite disks were significantly more active in reducing
      bacterial growth than the other dentifrices tested (P < or = 0.05). Finally, ex
      vivo treatment of oral bacteria with Colgate Total Advanced Fresh demonstrated a
      90.9% reduction of all oral cultivable bacteria and a 91.5% reduction of oral
      bacteria producing hydrogen sulfide compared with the control dentifrice. In
      conclusion, these results, taken together with the significant reductions in
      clinical malodor scores by Colgate Total Advanced Fresh demonstrated in
      organoleptic studies, strongly suggest that this dentifrice kills the bacteria
      that are implicated in the cause of bad breath.

PMID- 14692208
TI  - Clinical efficacy of Colgate Total Advanced Fresh and a commercially available
      breath-freshening dentifrice in reducing mouth-odor-causing bacteria.
AB  - The objective of this double-blind clinical study was to compare the long-lasting
      overnight (10- to 12-hour) and 4-hour effects of Colgate Total Advanced Fresh
      toothpaste to a commercial fluoridated breath-freshening dentifrice in
      controlling the level of mouth-odor-causing bacteria. Thirty-two adult men and
      women from New Jersey participated in the randomized, crossover design clinical
      study. After a 1-week "washout" period of brushing with a regular fluoride
      dentifrice, subjects refrained from dental hygiene, eating, and drinking in
      preparation for the morning visit. After providing a baseline salivary sample,
      subjects were issued a soft-bristled toothbrush and instructed to brush their
      teeth twice a day (once in the morning and once before bed) for 1 minute with the
      assigned test dentifrice. After a 7-day product use cycle, the subjects returned
      to the test site, having refrained from dental hygiene, eating, and drinking.
      Subjects provided an overnight salivary sample (10 to 12 hours postbrushing).
      Subjects then ate, brushed for 1 minute with the assigned dentifrice, and
      returned for 2- and 4-hour postbrushing evaluations. Subjects refrained from
      dental hygiene, eating, or drinking during the 4-hour evaluation period. To
      collect the oral microflora samples, subjects rinsed with 10 mL of sterile water
      for 10 seconds and deposited their samples into sterile tubes. Each collected
      sample was serially diluted in sterile phosphate-buffered saline and duplicate
      plated onto lead acetate agar. When plated onto this medium, mouth-odor-causing
      bacteria that produce hydrogen sulfide appear as dark pigmented colonies. After
      96 hours of incubation, hydrogen-sulfide-producing bacteria were counted,
      expressed as log colony-forming units per milliliter, and reduction from baseline
      was calculated. The results of this clinical study support the conclusion that
      Colgate Total Advanced Fresh provides a significantly greater reduction in mouth
      odor-causing bacteria than a commercial fluoridated breath-freshening dentifrice
      (P < or = 0.05).

PMID- 14692209
TI  - Breath-odor evaluation by detection of volatile sulfur compounds--correlation
      with organoleptic odor ratings.
AB  - Volatile sulfur compounds are known to be major contributors to oral malodor, and
      their detection by gas chromatography (GC) is a commonly used method for
      evaluating breath odor in clinical trials. A custom-designed breath-sampling GC
      system was developed for this purpose. A clinical study was performed to compare
      the performance of this instrumental method to organoleptic evaluation by trained
      odor judges. A statistically significant correlation was found between the
      measured levels of volatile sulfurs and the ratings of the odor judges. Both
      methods performed similarly in evaluating the breath-freshening effects of two
      test products. These results demonstrate the strength of the GC method for
      evaluating breath odor and predicting the breath-freshening effects of oral-care
      products.

PMID- 14692210
TI  - Clinical comparison of Colgate Total Advanced Fresh vs a commercially available
      fluoride breath-freshening toothpaste in reducing breath odor overnight: a
      multiple-use study.
AB  - The objective of this randomized, crossover study was to compare the
      effectiveness of Colgate Total Advanced Fresh toothpaste to a commercially
      available breath-freshening dentifrice containing fluoride for its ability to
      reduce volatile sulfur compounds (VSC) responsible for breath odor overnight. The
      study followed a two-treatment, two-period crossover design. Subjects were given
      a test product, along with a soft-bristled toothbrush, and instructed to brush
      their teeth for 1 minute, twice daily (once in the morning and the evening) using
      the assigned dentifrice for 7 consecutive days. After their evening brushing on
      the seventh day, subjects reported to the testing facility without oral hygiene,
      eating, or drinking for the overnight evaluation. After a washout period,
      subjects repeated the same regimen, now using the other test product. The levels
      of breath VSC were evaluated instrumentally using a gas chromatograph equipped
      with a flame photometric detector.

PMID- 14692211
TI  - Clinical effectiveness of a triclosan/copolymer/sodium-fluoride dentifrice in
      controlling oral malodor: a three-week clinical trial.
AB  - The purpose of this study was to compare the effectiveness of a commercially
      available, clinically proven, American Dental Association (ADA)-Accepted
      dentifrice containing 0.30% triclosan, 2% polyvinylmethylether/maleic acid
      (PVM/MA) copolymer, and 0.243% sodium fluoride in a 10% high-cleaning silica base
      (Colgate Total Advanced Fresh) to a commercially available, clinically proven,
      ADA-Accepted control dentifrice containing 0.243% sodium fluoride in a silica
      base (Colgate Cavity Protection Winterfresh Gel) for the management of oral
      malodor in a 3-week, randomized, double-blind longitudinal clinical trial. A
      panel of four expert judges used a nine-point hedonic scale to evaluate breath
      odor using a protocol designed in concordance with the ADA Draft Acceptance
      Program Guidelines for Products Used in the Management of Oral Malodor. After a
      baseline evaluation, prospective study subjects who scored above the threshold
      value for unpleasant breath odor were stratified by score and randomized into two
      treatment groups. Subjects were provided with a soft-bristled toothbrush and
      brushed their teeth thoroughly in their regular and customary manner for 1 minute
      with their assigned dentifrice, twice daily. Before oral-malodor evaluations, the
      subjects refrained from eating odorigenic foods and did not use dental hygiene
      procedures, breath mints, or mouth rinses. Eighty-one adult men and women from
      Chengdu, China, completed the study. Throughout the study, the mean breath-odor
      scores observed in the Colgate Total Advanced Fresh toothpaste group for both
      daytime and overnight were within the range of values associated with pleasant
      breath odor, were statistically significantly lower than the corresponding mean
      scores for the control group, and also represented statistically significant
      reductions from baseline. Relative to the baseline score, more than 80% of the
      subjects in the Colgate Total Advanced Fresh toothpaste group demonstrated a 3.2
      or more unit reduction in organoleptic scores at every postbaseline breath-odor
      evaluation. Thus, the overall results of the double-blind clinical study support
      the conclusions that Colgate Total Advanced Fresh toothpaste is efficacious for
      the control of oral malodor for up to 12 hours in the daytime and up to 12 hours
      overnight.

PMID- 14692212
TI  - A study of the compatibility of adhesives with composites.
AB  - A decade ago, the revolution in adhesion dentistry brought the profession to the
      basic three-step adhesives, such as ALL-BOND 2 and Adper Scotchbond MP, which
      were at the time deemed as fourth generation. However, the recent trend in
      adhesive products is to simplify the steps into two steps or even a single step
      to make them, possibly, more user-friendly and time saving. Subsequent naming led
      to a "generation battle." Is this the right track? Does this achieve
      simplification without compromising performance? Perhaps the best way to classify
      adhesives is to indicate the number of steps required. This article describes the
      results of a compatibility study of modern adhesive systems with composites in
      the fabrication of long-lasting and esthetic restorations.

PMID- 14692213
TI  - Advances in dentin adhesion.
AB  - While bonding to enamel has been a dependable technique, bonding to dentin is
      still an overwhelming task--dentin is a naturally soaked organic tissue. The
      enamel bonding agents of the 1960s and 1970s progressively evolved into complex
      multibottle or universal adhesives in the early 1990s. These multibottle systems
      were formulated to bond to enamel, dentin, composite, amalgam, porcelain, and
      nonprecious metal. More recently, simplified dentin adhesives were introduced
      following one of two adhesion strategies: total-etch adhesives that include an
      acid gel to remove the smear layer and dissolve hydroxyapatite (generally 30% to
      40% phosphoric acid for 15 to 30 seconds); and self-etching primers that treat
      the dentin and enamel with a non-rinsing solution of acidic monomers in water
      without removing the smear layer. Recent attempts to simplify the bonding
      procedure have led to the introduction of adhesives that do not use a separate
      acid-etch step and, therefore, do not etch enamel to the same depth as phosphoric
      acid-based dental adhesives.

PMID- 14692214
TI  - Histological evaluation of a self-priming etchant adhesive system.
AB  - Vital dentin is an extension of certain pulpal tissues, presenting the first line
      of defense against patient hypersensitivity and the long-term bacterial
      microleakage that can lead to recurrent caries and pulp inflammation. High-speed
      cavity preparation and forced air-drying of vital dentin causes the displacement
      of cells into vital dentinal tubules. However, after restoration, pulps recover
      and deposit reparative dentin deposition within 2 weeks. The purpose of the study
      discussed in this article was to observe the pulp healing response after cavity
      preparation and restoration with a total-etch or a calcium-hydroxide control.
      Teeth from adult monkeys were prepared with ultra-high-speed and water spray.
      Class V cavities were prepared and observed at three International
      Standardization Organization (ISO) time-usage periods. Tissues were collected
      following established procedures. A few pulps showed slight odontoblastic
      disruption at 7 days from cavity-preparation trauma. There was no pulp
      inflammation associated with any restorative system at the intermediate- and long
      time ISO time periods. There was less deposition of reparative dentin associated
      with the one-bottle Tyrian system than with the calcium-hydroxide control or the
      total-etch system.

PMID- 14692215
TI  - Single anterior tooth restoration using a self-etching adhesive system and a
      reinforced microfill composite.
AB  - Treatment for a single discolored anterior tooth may involve placement of a
      direct composite veneer to enhance a patient's smile and mask underlying
      discoloration. Among the challenges clinicians may face in this endeavor are the
      selection of suitable composite materials, application of an adhesive bonding
      system, and re-creation of the natural shade variations inherent in natural
      teeth. This article discusses the characteristics and placement protocol for a
      recently introduced self-etching adhesive system and a reinforced microfill
      composite when they are used to restore a single discolored central incisor.

PMID- 14692216
TI  - A new resin technology: a glaze/composite sealant that cures without forming an
      oxygen-inhibited layer.
AB  - Until now, intraoral composite resin sealants cured with an oxygen-inhibited
      layer. In addition, resin glazes used for temporaries and processed appliances
      could not be used intraorally. This article describes the strategies behind the
      development of a new resin product that can be used intra- and extraorally as a
      sealant/glaze without forming an oxygen-inhibited layer after curing.

PMID- 14692217
TI  - A new surface sealant for polishing composite resin restorations.
AB  - Achieving a smooth and lustrous surface in a timely fashion, using fewer steps,
      is a desirable feature for direct esthetic restorations. Eliminating the oxygen
      inhibition layer and converting it to a glaze layer removes any need for further
      polishing. This is more applicable to small restorations where reshaping and
      recontouring can be achieved before light-curing. Mechanical methods for the
      conversion of the oxygen-inhibition layer to a glazed surface include the use of
      a clear matrix and an oxygen-barrier gel. A new method has been developed to
      totally eliminate the formation of the oxygen-inhibition layer by chemical means.
      This includes the use of a highly reactive, multifunctional, acrylate-based,
      light-cured surface sealant and glaze, BisCover. This surface sealant may be
      applied to the surface of restorations before light-curing or after a brief
      curing. Additionally, it may be applied to the surface of a polymerized and
      reshaped restoration to remove the need for polishing. Existing composite resin
      restorations--hybrid or microfilled--as well as provisional acrylic restorations
      appear well polished and lustrous when surface sealant is applied and cured.
      Studies have shown that the microhardness of microfilled composite resin is not
      adversely affected by the use of a surface sealant.

PMID- 14692218
TI  - Advances in pediatric esthetic dentistry.
AB  - The introduction of low-shrinkage composite and no-rinse conditioners has created
      an opportunity for pediatric dentists to change their standard operative regimen.
      The low-shrink composite solves many of the problems that have discouraged
      clinicians from routinely providing posterior composites for their patients. The
      reduction in polymerization shrinkage decreases problems with contraction
      stresses, sensitivity, microleakage, recurrent caries, and negative pulpal
      sequelae. No-rinse conditioners simplify the process and shorten the time
      required for bonding procedures. Liquid polish reduces the tedious finishing
      previously required with resin-based composites. The combination of the easier
      bonding and more user-friendly composite could add a new operative technique to
      the pediatric dentist's armamentarium. A study of low-shrink, resin-based
      composite restorations was performed to determine the effectiveness of these new
      materials for pediatric dental practice. The restorations were placed in primary
      molars to allow for their retrieval when exfoliated. The preparation and
      restorative techniques were standardized to match a similar study that used the
      "open-sandwich" method. The modified US Public Health Service ranking was used to
      evaluate marginal integrity at 6-month intervals for the 40 restorations placed
      in primary molars as a pilot study. TESCERA ATL restorations and prostheses were
      also evaluated for clinical effectiveness.

PMID- 14692219
TI  - New concepts and technology for processing of indirect composites.
AB  - Indirect composites are becoming more popular as technology yields materials with
      increased mechanical properties while reducing occlusal wear with opposing teeth.
      Several of the indirect systems currently on the market use both light and heat
      catalysts in the same resin, which results in higher polymerization rates than
      light-curing alone. However, the order in which the indirect restoration is
      exposed to pressure and light may make a difference in the final properties of
      the prosthesis.

PMID- 14692220
TI  - Considerations for the successful placement of laboratory-processed, indirect
      composite restorations.
AB  - Adhesive bonding techniques enable clinicians to predictably place tooth-colored
      materials and thus provide viable alternatives to amalgam and other metal-based
      restorations. This is significant because patient demand for esthetic
      restorations is greater than ever before. Options for tooth-colored restorations
      include ceramics and direct and indirect composite-based materials. However,
      successful treatment using this restorative modality depends on a number of
      factors. This article reviews the case selection, preparation design, and
      material selection as they relate to indirect composite inlays and onlays.

PMID- 14692221
TI  - Predictable esthetic indirect restorations.
AB  - Patients are increasingly requesting esthetic tooth-colored restorations. Direct
      composite restorations have limitations based on the size of the restoration, the
      ability of the patient to tolerate procedures, and the ability of the dentist to
      provide functional restorations. The indirect composite restoration is ideal for
      replacing multiple failing restorations in teeth with existing restorations that
      are too large to be restored with direct composite restorations, yet too small to
      warrant the preparation for complete crowns.

PMID- 14692222
TI  - Single-visit, adjacent composite onlays--a dual-catalyst, inert gas-processed
      chairside technique.
AB  - Considerable research has been conducted on laboratory-processed composite resins
      in the last two decades. Substantial long-term studies support the theory that
      physical properties improve greatly if these composites are processed under high
      pressure inert gas. In addition, the use of dual catalysts (light and heat) will
      generate higher conversion rates in the composite. This article describes a
      clinical technique for fabricating adjacent onlays or three-quarter crowns in a
      single visit that capitalizes on the inert gas and dual-catalyst research.

PMID- 14692223
TI  - Burkitt's lymphoma of the scapula.
AB  - Burkitt's lymphoma may involve the maxilla or mandible, but to date, there has
      been no reference in the literature to scapular involvement by this tumor. This
      article describes the case of a 9-year-old child who presented with a huge tumor
      involving the right shoulder with osteolytic and sclerotic lesions in the
      scapula. The histopathological findings were suggestive of Burkitt's lymphoma,
      and the immunohistochemical findings discard a lymphoblastic lymphoma or
      plasmablastic lymphoma. In addition, in situ hybridization for Epstein-Barr virus
      encoded small nuclear RNA (EBER) was positive. Although the child also presented
      a cervical lymphadenopathy, the fact that Burkitt's lymphoma is generally
      extranodal, the marked swelling of the shoulder, and the extensive involvement of
      the bone strongly argue that this tumor had its origin in the scapula. This case
      demonstrates the importance of including Burkitt's lymphoma in the differential
      diagnosis of lymphoma involving bones in children.

PMID- 14692224
TI  - Warfarin embryopathy.
AB  - A 34-year-old gravida 2 para 1 (1001) mother was on prophylactic anticoagulation
      therapy because of pulmonary emboli postabdominal surgery. The pregnancy was
      terminated at 25 weeks' gestation after ultrasound examination showed a mild
      hydrocephalus and a cardiac structural defect. Congenital abnormalities of the
      delivered fetus included nasal hypoplasia, earfold atresia, bilobled lungs,
      coarctation of the aorta, ventricular septal defect, gastrochisis, and
      radiographic skeletal stippling. The radiological and physical findings were
      consistent with warfarin embryopathy.

PMID- 14692225
TI  - Clinico-pathologic conference: a 7-year-old girl with fever and lymphadenopathy.

PMID- 14692226
TI  - Classification of M nontypeable group A streptococcus with the use of field
      inversion gel electrophoresis.
AB  - Group A streptococcus (GAS) are traditionally classified based on M and T protein
      antigens. However, many strains do not react with available M antisera and are
      classified as M nontypeable (M NT). M and T typing, field inversion gel
      electrophoresis (FIGE), and 5' emm gene sequencing were performed on 24 M NT GAS
      isolates. FIGE patterns of the M NT isolates were compared by visual inspection
      and by computer analysis with the patterns of 139 isolates representing 72 M
      types of GAS. Seven different FIGE patterns (I-VII) were seen among the M NT
      isolates. FIGE patterns I and III were identical or closely related to patterns
      seen with M12 and M22 isolates. The computer analysis determined the following
      relationships: pattern IV to M5, pattern VI to M61, and pattern VII to M59. Thus,
      the emm gene sequence correlated with the computer analysis of the FIGE pattern
      for each isolate. FIGE can be useful to help distinguish clinical isolates of GAS
      in an epidemiological study.

PMID- 14692227
TI  - In vitro proteoglycan sulfation derived from sulfhydryl compounds in sulfate
      transporter chondrodysplasias.
AB  - Mutations in a sulfate-chloride antiporter gene, the diastrophic dysplasia
      sulfate transporter (DTDST), have been associated with a family of skeletal
      dysplasias including recessive multiple epiphyseal dysplasia, diastrophic
      dysplasia (DTD), atelosteogenesis type 2, and achondrogenesis type 1B (ACG1B).
      DTDST function is crucial for uptake of extracellular sulfate required for
      proteoglycan (PG) sulfation; the tissue-specific expression of the clinical
      phenotype may be the consequence of the high rate of PG synthesis in chondrocytes
      and the ensuing high sulfate requirement. We have studied the contribution of
      cysteine and its derivatives to PG sulfation in fibroblast and chondrocyte
      cultures from sulfate transporter dysplasia patients. Incubation of ACG1B
      fibroblasts in medium containing different concentrations of cystine indicated
      partial recovery of PG sulfation as measured by HPLC disaccharide analysis of
      chondroitin sulfate PGs; similar results were observed after incubation with N
      acetylcysteine. When both compounds were tested in primary chondrocytes from a
      DTD patient, partial rescue of PG sulfation was observed, suggesting that the
      metabolic pathways producing cytoplasmic sulfate from thiols are also active in
      this cell type.

PMID- 14692228
TI  - Neoplastic disease and deletion 22q11.2: a multicentric study and report of two
      cases.
AB  - Deletion 22q11.2 is a chromosomal abnormality detected in young patients with
      clinical manifestations of the DiGeorge/velocardiofacial syndrome. Conotruncal
      heart defects are also associated with del22q11.2. An association of these
      cardiac malformations with neoplasias has been observed. Our series includes two
      cases of malignancies, a hepatoblastoma and a renal-cell carcinoma, arising in
      children with complex cardiac malformations. The aim of the study was to
      determine if the deletion at 22q11.2 was present and could be responsible for
      both pathological processes. Del22q11.2 was identified in both cases. Comparative
      genomic hybridization revealed terminal gains on chromosomes 1q and Xq and
      terminal loss on 1p in the hepatoblastoma, and gains in 1p, 12q, 16p, 20q, 22q,
      and whole chromosome 19 and loss of Xq in the renal-cell carcinoma. Our results
      confirm a common genetic basis for cardiac malformations, and del22q11.2 presents
      a risk factor for the development of pediatric tumours.

PMID- 14692229
TI  - Yolk sac tumor and testicular microlithiasis.
AB  - Yolk sac tumor (YST) of prepubertal testis is a peculiar neoplasm with overall
      good prognosis. There are no known conditions associated with the development of
      this tumor. The case of a 2-year-old boy with testicular YST and presence of
      testicular microlithiasis (TM) in the adjacent-still-recognizable testicular
      tissue is reported. Concentrically laminated microliths were clearly extratubular
      structures. Ultrasound of the remaining testis revealed microlithiasis. Bilateral
      TM is being recognized with increasing frequency due to the extensive use of
      ultrasound. The exact meaning of its finding has not been definitively
      elucidated, but the association of TM with cryptorchidism, intratubular germ cell
      neoplasia and germ cell tumors either of the testis or mediastinum is on record.
      The combination of prepubertal YST and bilateral TM has not been reported
      previously. Finding of TM at this early age suggests a congenital deranged
      Sertoli cell function and/or an abnormal gonadal embryogenesis in its
      pathogenesis.

PMID- 14692230
TI  - Divergent patterns of extracellular matrix protein expression in neonatal versus
      adult liver fibrosis.
AB  - The extracellular matrix (ECM) expression is subject to distinct changes during
      ontogeny, and the natural course of liver fibrosis in neonates is thought to
      differ from that in adults. We compared the expression and distribution of main
      ECM components between neonatal and adult liver fibrosis. Liver biopsies from
      infants with neonatal cholestasis and fibrosis were compared to adult biopsies
      exhibiting an equivalent stage of fibrosis. All biopsies were examined by
      immunohistochemistry (indirect ABC method) for the ECM proteins, collagens I,
      III, IV, and VI, laminin, and fibronectin. Infants (aged 1-8 months) with
      neonatal hepatitis (n = 3), extrahepatic biliary atresia (EHBA) (n = 5), and
      normal histology (n = 2) were compared with 9 adults (aged 17-70 years) with
      chronic hepatitis (n = 3), primary biliary cirrhosis (PBC) (n = 4), and normal
      histology (n = 2). Collagens I, III, and IV and fibronectin were significantly
      increased in neonatal hepatitis with mild fibrosis (score < or = 4) compared to
      adults with an equivalent fibrosis stage. This increase was particularly notable
      in perisinusoidal spaces. Laminin expression was increased in portal and
      perisinusoidal spaces both in neonatal hepatitis and extrahepatic biliary atresia
      with mild fibrosis. In infants with moderate to severe fibrosis (score > or = 6),
      only collagen I was increased in comparison to adults, whereas collagen VI
      expression was identical in all groups, irrespective of the degree of fibrosis.
      Expression of matrix proteins was not different in infants and adults without
      fibrosis. The increased perisinusoidal deposition of certain ECM components in
      infants with active hepatitis and mild fibrosis may point to an underlying
      difference in the mechanism or stimulus of fibrogenesis in neonates as compared
      to adults.

PMID- 14692231
TI  - Pathology teach and tell: nasopharyngeal angiofibroma.

PMID- 14692232
TI  - A thalassemic child becomes adult.
AB  - In the last decades, treatment of patients with beta-thalassemia has changed
      considerably, with advances in red cell transfusion and the introduction of iron
      chelation therapy. This progress has greatly increased the probability for a
      thalassemic child to reach adult age with a good quality of life. At present, the
      prognosis for thalassemia major patients is "open-ended". Compliance with the
      conventional treatment and psychological support are critical to obtain good
      results. The expectancy of a long survival of good quality encourages the
      patients to plan their future life, having a job, a family and often children.
      Optimal treatment of thalassemia major is expensive and for this reason,
      unfortunately, available only for a minority of patients in the world. Despite
      the significant advances, other progresses are expected to further improve
      survival and quality of life. The major aim is the cure of the disease,
      increasing the possibility of bone marrow transplantation using HLA-matched
      unrelated donors, and hopefully, in the future, gene therapy. However, even the
      conventional treatment and in particular iron chelation is expected to improve.
      Efforts should be made by the Western countries, and by the international health
      and economic organizations to provide continuous and concrete support for
      achieving a high standard of management for thalassemia in all places of the
      world.

PMID- 14692233
TI  - Red blood cell membrane defects.
AB  - We present an overview of the currently known molecular basis of red cell
      membrane disorders. A detailed discussion of the structure of the red cell
      membrane and the pathophysiology and clinical aspects of its disorders is
      reported. Generally speaking, hereditary spherocytosis (HS) results from a loss
      of erythrocyte surface area. The mutations of most cases of HS are located in the
      following genes: ANK1, SPTB, SLC4A1, EPB42 and SPTA1, which encode for ankyrin,
      spectrin beta-chain, the anion exchanger 1 (band 3), protein 4.2 and spectrin
      alpha-chain, respectively. Hereditary elliptocytosis (HE) reflects a diminished
      elasticity of the skeleton. Its aggravated form, hereditary pyropoikilocytosis
      (HPP), implies that the skeleton undergoes further destabilization. The mutations
      responsible for HE and HPP, lie in the SPTA1 and SPTB gene, and in the EPB41 gene
      encoding protein 4.1. Allele alpha LELY is a common polymorphic allele, which
      plays the role of an aggravating factor when it occurs in trans of an
      elliptocytogenic allele of the SPTA1 gene. Southeast Asian ovalocytosis derives
      from a change in band 3. The genetic disorders of membrane permeability to
      monovalent cations required a positional cloning approach. In this respect,
      channelopathies represent a new frontier in the field. Dehydrated hereditary
      stomatocytosis (DHS) was shown to belong to a pleiotropic syndrome: DHS + fetal
      edema + pseudohyperkalemia, which maps 16q23-24. Splenectomy is strictly
      contraindicated in DHS and another disease of the same class, overhydrated
      hereditary stomatocytosis, because it increases the risk of thromboembolic
      accidents.

PMID- 14692234
TI  - Role of apoptosis in congenital hematologic disorders and bone marrow failure.
AB  - Apoptosis, the cell's intrinsic death program, plays a critical role in the
      regulation of tissue homeostasis, especially in cell systems with a high turnover
      rate such as hematopoiesis. Imbalances between survival, proliferation and death
      of precursor cells or mature cells may result in accelerated loss or impaired
      output or uncontrolled polyclonal or monoclonal expansion and may pave the way to
      the development of leukemia. Congenital hematologic disorders are characterized
      by disturbed growth control of hematopoietic cells. In the previous years, it has
      become clear that deregulated apoptosis contributes or is even a key determinator
      of the pathophysiology of diseases such as lymphoproliferation, aplastic anemia
      or chronic neutropenia. Hematopoietic growth factors have been shown not only to
      stimulate proliferation of hematopoietic stem cells and committed precursor
      cells, but also to act as survival factors protecting developing precursor cells
      from apoptotic signals. The molecular delineation of pathways of apoptosis
      signaling or survival in hematopoietic cells is expected to provide tools for
      molecular understanding of the pathophysiology of congenital and acquired
      hematopoietic disorders and to identify targets for therapeutic intervention
      strategies.

PMID- 14692235
TI  - Congenital neutropenias.
AB  - The term congenital neutropenia (CN) has been used for a group of hematologic
      disorders characterized by severe neutropenia with absolute neutrophil counts
      (ANC) below 0.5 x 10(9)/L associated with increased susceptibility to bacterial
      infections. This group of diseases includes primary bone marrow failure syndromes
      with isolated neutropenias and neutropenias associated with metabolic or
      immunologic disorders or with a complex syndrome. To avoid confusion, we prefer
      using the term CN only for the most severe disorder among this group: severe
      neutropenia characterized by an early stage maturation arrest of myelopoiesis
      leading to bacterial infections from early infancy. This disease has originally
      been described as Kostmann syndrome with an autosomal recessive inheritance.
      Recent pathogenetic investigations have demonstrated that this clinical phenotype
      includes also autosomal dominant and sporadic cases with different point
      mutations in the neutrophil elastase gene in a subgroup of patients. Data on over
      400 patients with CN collected by the Severe Chronic Neutropenia International
      Registry demonstrate that independent from the CN-subtype more than 90% of these
      patients respond to recombinant human granulocyte-colony stimulating factor (rHuG
      CSF filgrastim, lenograstim) with ANC that can be maintained around 1.0 x
      10(9)/L. Adverse events include mild splenomegaly, moderate thrombocytopenia,
      osteoporosis and malignant transformation into myelodysplastic syndrome/leukemia.
      Development of additional genetic aberrations, e.g., G-CSF-receptor gene
      mutations, monosomy 7 or ras mutations during the course of the disease indicate
      an underlying genetic instability leading to an increased risk of malignant
      transformation. If and how G-CSF treatment impacts on these adverse events
      remains unclear since there are no historical controls for comparison.
      Hematopoietic stem cell transplantation is still the only available treatment for
      patients refractory to G-CSF treatment.

PMID- 14692236
TI  - Primary immune deficiencies unravel the molecular basis of immune response.
AB  - Primary immune deficiencies (PID) represent inborn errors of immunity. Over the
      years, detailed analysis of the clinical and laboratory features associated with
      these unique and rare disorders have shed light on the complex array of signals
      and processes that govern development and activation of the immune system. While
      the first examples of PID pertained to severe defects in lymphoid development,
      more recently a variety of gene defects have been identified in humans that do
      not compromize the ability to generate lymphocytes, but rather result in profound
      immune dysregulation. In many cases, identification of the molecular and cellular
      bases of PID has preceeded development of animal models by gene targeting.
      Finally, since the very first cases reported in humans, PID have also represented
      a unique tool to investigate the efficacy of novel therapeutic approaches (from
      molecular therapy to hematopoietic stem cell transplantation to somatic cells
      gene therapy), that have been applied or may apply to a variety of more common
      human diseases.

PMID- 14692237
TI  - What is in store for 2004? Rapid review will mean cutting edge information to
      you!

PMID- 14692238
TI  - A tribute to Doris Schwartz. 1999 Doris Schwartz award presentation.

PMID- 14692239
TI  - Adult day programs. Who needs them?

PMID- 14692240
TI  - Creating a therapeutic psychosocial environment in dementia care. A preliminary
      framework.
AB  - Research in dementia care during the past few years has focused on identifying
      and designing therapeutic physical environments while the psychosocial
      environment has remained a largely unexplored domain. More recently, discussions
      regarding the effect of the social environment on individuals with dementia have
      increased in the literature. Nevertheless, the authors suggest the term "social
      environment" does not adequately represent the critical psychological and
      emotional effect social interaction has on individuals with cognitive impairment.
      Through an examination of the literature, three conceptual frameworks, and
      clinical observations of several special care units (SCUs), the authors suggest
      that the psychosocial environment is the most important element of institutional
      dementia care. A preliminary conceptualization is offered which identifies the
      elements necessary to facilitate a supportive psychosocial environment in long
      term care. The potential benefits of implementing such a model include
      preservation of personhood, simple recognition of remaining abilities and a
      decreased focus on disabilities, and reduction of pharmacologic therapy for
      disruptive behavior resulting in overall improvement in quality of life.

PMID- 14692241
TI  - Older adults with osteoarthritis. Psychological status and physical function.
AB  - The purpose of this study was to identify how sociodemographic characteristics
      such as age, race, and socioeconomic status; psychosocial factors of hardiness,
      health promotion practices, and social support; health status; and pain are
      related to the ability of older, community-residing individuals with
      osteoarthritis (OA) to maintain psychological equilibrium and physical function.
      A total of 81 older adults with OA completed a survey that included a
      sociodemographic data form, a hardiness scale, a measure of health promoting
      practices, and five subscales from the Arthritis Impact Measure Scale 2 on social
      support, general health status, pain, and psychological status and physical
      function. Analyses using multiple regression showed that hardiness, pain, and
      social support were significant contributors to psychological status and physical
      function and, respectively, accounted for 53% and 54% of the variance. By knowing
      about OA and being aware of factors that contribute to maintaining independence
      in individuals with OA, nurses can provide expert help to aging individuals.

PMID- 14692242
TI  - Heart failure in older adults. Providing nursing care to improve outcomes.
AB  - Heart failure continues to be a challenge for older patients and their health
      care providers. This article is based on work by advanced practice nurses in a
      nursing study funded by the National Institute of Nursing Research of the
      National Institute of Health. Mary Naylor, RN, PhD at the University of
      Pennsylvania School of Nursing through grant #1RO1-NR04315 is using a
      transitional care model to provide advance practice nurse intervention for older
      adults with heart failure in a randomized controlled trial. Effects of the
      intervention being addressed include quality of life, functional status,
      rehospitalizations, and costs of care. Working with the patient in the acute
      hospital setting and following patients to the home care setting for 3 months,
      the advance practice nurse develops a visit pattern and intervention plan
      individual to the patient's needs. Key to a successful intervention plan is the
      right treatment for systolic versus diastolic failure. Although the patient's
      symptoms and some physical findings may be similar, the drugs used to treat
      systolic versus diastolic heart failure are different. Thus the nursing
      interventions to promote symptom management and avoid rehospitalizations have a
      different approach. In this article, care of elderly individuals with systolic
      versus diastolic heart failure is compared and contrasted using physical
      examination and diagnostic techniques, medication management, and nursing
      intervention. Case studies of a typical patient with systolic and diastolic heart
      failure will be used to illustrate the differences in approach to this common
      group of patients with complex needs.

PMID- 14692243
TI  - Resilience and successful aging. Comparison among low and high income older
      adults.
AB  - 1 Resilience, a personality characteristic that moderates the negative effects of
      stress and promotes adaptation, has been associated with better health in prior
      studies. 2 Successful aging can be defined as the enjoyment of health and vigor
      of the mind, body, and spirit into middle age and beyond. 3 Individuals with
      lower incomes may be less likely to achieve successful aging because of a higher
      prevalence of health risk factors. 4 Resilience appears to be positively and
      significantly associated with indicators of successful aging regardless of
      income.

PMID- 14692246
TI  - Partnerships are key to quality care.

PMID- 14692250
TI  - Net gains for haemophilia patients.

PMID- 14692251
TI  - Varicella-zoster virus, shingles and postherpetic neuralgia.

PMID- 14692252
TI  - Should dementia patients be informed about their diagnosis?
AB  - Current government policy encourages service users to be involved as equal
      members of the interprofessional care team. This goal is compromised in the care
      of people with dementia if they are not informed of their diagnosis. This paper
      looks at recent research both for and against disclosure, and argues in favour of
      breaking the news in a supportive way.

PMID- 14692253
TI  - Are link-nurse systems an effective means for improving patient care?
AB  - Link nurses are part of a system that shares information and provides formal, two
      way communication between specialist teams and nurses in the clinical area. Many
      different clinical areas might employ such nurses, including tissue viability and
      diabetes. Link-nurse systems have the potential to promote and enhance clinical
      effectiveness and disseminate research findings.

PMID- 14692254
TI  - A study to investigate high readmission rates for COPD.
AB  - When an NHS trust found it had high readmission rates among patients with chronic
      obstructive pulmonary disease, nurses from the acute respiratory assessment
      service decided to find out why. An audit found that, in fact, a very small
      number of patients were the cause of the problem. They suggest that improved care
      at home after discharge could help resolve the issue.

PMID- 14692255
TI  - A model to help nurses caring for patients who are terminally ill.
AB  - In an age when people are no longer automatically dying from serious illnesses
      such as cancer or heart disease, patients, families and health-care staff may
      find coping with a terminal illness difficult. A multidisciplinary team in one
      hospital used Moos' transitional model, which describes adaptive and coping
      techniques, in their care of a dying man and his family.

PMID- 14692256
TI  - The effects of passive smoking on adult and child health.
AB  - Forty-two per cent of UK children live in a household where someone smokes. This
      paper, the third in a series on smoking cessation, presents a brief review of the
      evidence concerning the impact of passive smoking on adult and child health. It
      outlines some harm-reduction approaches aimed at reducing the impact of passive
      smoking at home, at work and in public.

PMID- 14692257
TI  - The benefits of setting up a nurse hysteroscopy service.
AB  - Many nurses are extending their roles in line with the Government's NHS Plan. In
      the outpatient hysteroscopy service in one trust nurses are now undertaking
      diagnostic hysteroscopy. This has improved continuity of care for patients and
      allowed the nurses to combine their traditional nursing role of providing
      information and reassurance with performing the procedure.

PMID- 14692258
TI  - Using clinical research summaries to aid research nurses.
AB  - The National Cancer Research Network was introduced in 2001 with the aim of
      doubling the number of cancer patients undergoing clinical trials. Clinical trial
      summaries are an invaluable tool for busy research staff, providing a precis of
      current research taking place in an organisation. They can be used in research in
      any clinical area and in hospital or community.

PMID- 14692259
TI  - Nurses put men's health in spotlight.

PMID- 14692260
TI  - Nurse-led clinics for assessing men with lower urinary tract symptoms.
AB  - The growing ageing population is leading to an increase in the number of men
      presenting with lower urinary tract symptoms. This paper argues in favour of more
      nurse-led clinics offering a holistic approach to assessing this condition that
      take account of local needs. New guidelines from the British Association of
      Urology Nurses are also discussed.

PMID- 14692261
TI  - Developing an innovative approach to tackling men's health issues.
AB  - Men are notoriously reluctant to seek health advice, particularly if it involves
      urological problems. A multidisciplinary team in Northern Ireland came up with
      some innovative initiatives to address some major health issues facing men in
      their community, involving meetings in a pub and a mosque, and a men's health
      roadshow.

PMID- 14692262
TI  - Patient information: Part 3. Collecting high-quality evidence.

PMID- 14692263
TI  - Casebook: behavioural problems.

PMID- 14692264
TI  - Managing the obese child.

PMID- 14692265
TI  - The sexually abused child.

PMID- 14692266
TI  - Tackling the video component.

PMID- 14692268
TI  - A comparison of the levels of patient anxiety and knowledge of different
      treatment modalities in different clinical settings in Cardiff.

PMID- 14692269
TI  - Sedation: entity or continuum.

PMID- 14692270
TI  - British Dental Acupuncture Society. Annual scientific meeting.

PMID- 14692271
TI  - Letter from the Secretary.

PMID- 14692272
TI  - [Research and post-graduate studies: regulation/qualification of the nursing
      practice].

PMID- 14692273
TI  - [Mother-child bonding: comparative study of mothers after normal delivery and
      cesarean section].
AB  - The authors chose behavior observation through continuous and specific cursive
      recording. The purpose was to compare the behavior of mothers and natural-birth
      newborns with that of caesarian section newborns in their first 24 hours of life
      in rooming-in. Fourteen mother-child pairs, seven natural births and seven
      caesarian sections were observed. The observation led to useful conclusions
      related to nursing care. The mothers' voice and the way they fondle newborns can
      be indicators of their willingness to take care of the baby. Mothers who have
      caesarian sections need more attention to begin breastfeeding. In both groups,
      mothers improved better performance in caring for their newborns over the
      postpartum period. Inexperienced or fragile mothers need more postpartum
      attention. The environment can influence the establishment of successful ties.

PMID- 14692274
TI  - [Non-verbal communication of patients with intestinal cancer treated with
      ostomy].
AB  - The purpose of this article is to analyze the nonverbal communication of the
      participants in a group of bowel cancer ostomy bearers. The type of the
      investigation was exploratory and observational. The investigation was carried
      out in a Teaching Hospital. The population was composed by 5 persons, bearing
      ostomy due to bowel cancer. There were 5 meetings in October and November of
      2001. Data was gathered through video recording and field notes. Among the
      findings we remark the room small size forced the participants to maintain a very
      close distance that led in difficulties for their spontaneous expression. This
      article clarifies that the reading of the nonverbal communication enabled the
      understanding the universe of the investigated persons.

PMID- 14692275
TI  - [The experience of the family caring for a relative with cancer].
AB  - The proposal of this study is to understand the kind of care developed by family
      members of patients suffering from cancer, in order to help and support them in
      such a difficult situation. The study also aims at understanding the experience
      the family goes through by identifying the kind of feelings family members
      experience during the period of the disease. We will adopt a qualitative approach
      having symbolic interacionism as our theoretical reference. It was observed that
      in order to take care of the patient the family develops several forms of support
      and care, thus creating new ways to function in this situation. While caring for
      the patient the family expresses its feelings and its interpretation of the
      situation.

PMID- 14692276
TI  - [Madness in freedom: experiences in Crato-CE (1930-1970)].
AB  - This study aims at identifying the most meaningful characters in the social
      imaginary and narrating its experience. This is a social-historical study in
      which oral (semi-structured interviews) and written documental sources were used.
      The interpretation of data was based on the archeological studies by Foucault on
      the history of madness and on other authors who worked with the themes:
      psychiatric madness and psychiatric reform. The narration of madness in the
      scenery of Crato indicates the existence of a multiplicity that reveals
      diversity, transcending the traditional psychiatric paradigm, which has as its
      principle the idea that the "mad person" should be isolated from society. We
      expect that this study contribute to the debate of nursing professional in the
      field of psychiatric and mental health.

PMID- 14692277
TI  - [Opinion of nursing students on mental disease and care in the area].
AB  - The authors aim at investigating the knowledge on mental diseases and treatments
      among nursing students that are entering the job market. In This descriptive
      study A Likert-like scale of opinion measurement, with 56 statements related to
      the topic of the study was applied. The responses of the 38 students who
      participated were analyzed and grouped in four categories:--Patient, family and
      care,--Psychiatric policies and care,--Conceptions on the disease and the
      patient,--Nursing care and treatments. Results showed that the subjects believe
      that not all social problems and diseases have to be treated at the psychiatric
      institutions since there are other alternatives to solute these problems. They
      also pointed out the importance of family participation and professionals'
      development in order to improve the quality of the care.

PMID- 14692278
TI  - [Nursing research and epidemiologic profile of the northeast].
AB  - This study aim at analyzing the relationship between the epidemic profile of the
      Brazilian Northeastern region and the scientific production of the Masters Degree
      Program in Nursing/UFC, through the identification of the themes researched
      between 1995 and 2001. In order to achieve these objectives, we developed an
      exploratory and descriptive study which had as its primary source data from
      OPAS/OMS, demographic and socioeconomic indicators and IDB for 2000, which
      reflected on the classification of themes according to the "Categorical Scheme
      for Lines of research". Results showed that most of the scientific production in
      this program relates to the following lines of research: life quality and
      determinants of disease and health (71.3%) which relates to the assistance field
      and "technology in nursing" (57.2), which relates to the professional field. We
      believe that these two lines of research are in accordance with the priorities of
      research of CNPq (National Research Council) and that they meet social demands.
      We suggest the development of research related to children's and elderly's health
      as well as violence in order to meet the needs generated by the epidemic profile
      of the Northeastern region.

PMID- 14692279
TI  - [Lato sensu post-graduation in psychiatric nursing and mental health: history,
      institutional context, and actors].
AB  - The theme of this study is "latu sensu" post-graduation teaching in nursing
      psychiatry and mental health in EE/UFRGS and EERP/USP nursing schools. In this
      study we characterize this courses and the profile of its professors. Through the
      analysis of the teaching plans, programs and documents of the specialization
      courses, as well as through the analysis of semi-structured interviews, we
      obtained data regarding the history and structure of these courses, which were
      pioneers and motivators of the specialized education in this field. The
      characterization of the courses will be done through the presentation of its
      timetable, number of disciplines, professional titles, and development of the
      professors involved, in order to show how psychiatry nursing and mental health
      teaching has been constituted.

PMID- 14692280
TI  - [Reflection on the significance of the family health theme in the teaching of
      nursing graduate studies].
AB  - This study is about the insertion and performance of the recently graduated
      nurses in the Family Health Program (FHP). Its aims are: to analyze the
      contributions of the educational process for the nursing practice in the FHP; to
      verify if nursing professionals feel secure about their capacity to work FHP
      after going through the nursing course with its specific curriculum; to discuss
      the difficulties faced by these professionals in this program. This is a
      qualitative, descriptive and analytical research. Data was obtained through
      semistructured interviews with 15 nursing professionals graduated since 1997.
      Through data analysis two categories were identified: the first was the
      professional qualification of first aid nursing professionals, the second was
      difficulties and satisfaction of these professionals as participating in the FHP.
      Results showed that there is a need for a better approach regarding family health
      in the undergraduate courses.

PMID- 14692281
TI  - [Knowledge and practice of adolescents in the prevention of sexually transmitted
      diseases].
AB  - This study aims at evaluating the knowledge of adolescents regarding the
      prevention and transmission of DST's, HIV/AIDS. It was carried out in a school in
      the city of Canoas/RS. 121 students, with age between 12-19 participated in the
      study. According to the interviews 22.3% said that their sexual life starts at
      the age between 12 and 16. Student's knowledge regarding the transmission of
      DST's is evident, since 79% of the students pointed out that those diseases are
      transmitted through sexual contact if there is no use of condoms. However some
      myths and stereotypes related to these disease were also identified. 16.3% of the
      adolescents believe that contamination can occur in bathrooms, swimming pools and
      saunas.

PMID- 14692282
TI  - [Underreporting of accidents with cutting and piercing objects in nursing].
AB  - This study aimed at: identifying occupational accidents caused by percutaneous
      injuries among nursing workers, identifying whether or not accidents were
      reported and at learning about the reason for non-reporting. It is a descriptive
      study with a quantitative analysis of the data collected through the interview
      technique applied to 394 nursing workers from two hospitals in Sao Paulo State.
      The results showed that 30% of the 394 workers had an accident in 2001 and of
      such accidents, 277 (70.30%) were caused by percutaneous injuries, 173 (62.45%)
      accidents were reported and 104 (37.55%) were not reported. The reasons leading
      to non-reporting were related to beliefs, lack of knowledge and information
      concerning contamination risks and to the form of data recording.

PMID- 14692283
TI  - [Sick bodies textualized through images: what contemporary intensive care units
      can teach us].
AB  - This paper belongs to a dissertation in which, what we have call "nursing worker
      cyborgizing" in intensive therapy is discussed. In order to carry out this
      discussion we based our work on cultural theorizing, as well as on Donna Haraway
      understanding of cyborg. For the corpses analysis manuals and assistance
      protocols were used. The methodological approach used in this work is the
      cultural analysis, as it has been used in the Poststructuralist Cultural Studies,
      in order to describe and analyze the production of images of sick bodies and its
      decoding process through a complex monitoring system in which sick bodies,
      machines and nursing practitioners, connect in different ways and effects. We
      have concluded that it is useful and relevant to consider and discuss these
      instances of production and diffusion of meanings attributed to the body, life,
      and the Nursing care.

PMID- 14692284
TI  - [Use of video recording technique in nursing research on children's health].
AB  - This study aims at describing the methodological approach adopted in an
      investigation on nursing care in the follow-up of children's growth and
      development in a Basic Health Unit, focusing on the videotaping technique. The
      study discusses aspects of the exploratory phase, empirical data collection,
      recording and observation unit by emphasizing the use of video recording as well
      as its advantages and difficulties.

PMID- 14692285
TI  - [Epidemiologic surveillance in the local health system].
AB  - This is a qualitative study, which aims at analyzing the organization of
      Epidemiological Vigilance (EV) in the local health system of Feira de Santana-BA,
      from 1997 to 2001 > in this study the following aspects were considered:
      organizational structure, resources available (human and material ones),
      planning, execution, intra and interinstitutional and intersectional
      articulations, considering the insertion of the city in the "Basic assistance
      Program". The collection of data was carried out in 3 stages: documental
      analysis, semi-structured interviews and direct observation with the VE. team.
      Results revealed that there are frequent changes in the management positions of
      VE. The structure, centralized in the SMS, prioritizes programmatic actions which
      are not articulated to the network of services offered. Advances can be noticed
      in the infrastructure, despite the lack of equipment and the deficiency in the
      qualification the human resources. The transformation of the model of health
      assistance is possible if health professionals, managers and users have political
      interest in changing it the practices in health services.

PMID- 14692286
TI  - [Written communication: contribution to the development of educational material
      in health].
AB  - Communication is an indispensable tool in the context of the assistance; the
      written form is widely used in the educational activities in health. This article
      describes aspects related to the language, illustrations and layout that health
      professionals should consider when elaborating educational printed material, in
      order to make it legible, understandable, efficient and culturally relevant.
      Considering the great contribution of written material in the context of
      education in health and the role of these resources to promote health, to prevent
      illnesses, to develop skills, to favor patient's autonomy, one concludes that it
      is important to create, to develop and to produce qualified material which can
      the patient's needs.

PMID- 14692287
TI  - [Humanization and nursing work].
AB  - In this work we have as our objective to reflect on the theme of the 63rd. Annual
      Nursing Week "Humanization and Work: reason and meaning in Nursing". We discuss
      the relationship between humanization/work in nursing, differentiating the
      aspects related to the humanization of nursing work to those of the humanized
      work in nursing. The challenges of the process of humanization of assistance and
      of work relationships imply on the overcoming of the relevance given to the
      technical scientific competence, routine patterns which are crystallized,
      conventional models of management, corporativism of the different professional
      categories in favor of interdependence and the complementarity in health actions;
      construction of an utopia of the humanization as collective process which can be
      reached and implemented.

PMID- 14692288
TI  - [On the tracks of ethnography: reflections on nursing knowledge].
AB  - This study presents a reflection on ethnography, as a means for developing
      knowledge in nursing. From the anthropologic conception of ethnography, and the
      comparison of a few studies by nurses who have used ethnography as a
      method/methodology in their research, considerations are made about problem
      solving techniques, the theoretical framework, the option for ethnography as a
      methodological mean, the conception and involvement with fieldwork and the
      ethnographic text developed within the nursing care setting. A few implications
      are then presented, making possible to perceive a special way "ethnonursing" has
      to contribute towards the discipline of Nursing.

PMID- 14692289
TI  - [The role of nursing in percutaneous cervical cordotomy in the control of
      oncologic pain].
AB  - Oncological pain is usually progressive and enabling. One third of the patients
      under treatment and two thirds of the patients with advanced cancer refer to
      pain. Generally treatment starts with non-opioids analgesic medicines and other
      drugs, passing to opioids with a progressive increase of the doses and
      neurosurgical procedures when recommended. Percutaneous cervical cordotomy is a
      neurosurgery procedure to treat unilateral cancer pain, especially in
      extremities, which gives immediate relief and low morbidity. The nursing
      professional plays an indispensable role in the effectiveness of this treatment.
      For this reason the author decide to report on this experience.

PMID- 14692290
TI  - [Historicizing nursing and patients at a psychiatric hospital].
AB  - This is a historical research whose objective is to historicize the nursing team
      and the patients at the Hospital Colonia Sant'Ana (HCS), in the period from 1941
      to 1960. Five employees that worked at the Hospital in the period of the study
      were interviewed and other documental sources were used. To analyze the data
      Foucault's theory was used. HCS was the main pole of psychiatric care in the
      Santa Catarina. The nursing team was constituted by the nuns, "male nurses" and
      "watchmen". The institution received indigent, private, and health insurance
      covered patients, who were diagnosed with many different problems, and some who
      were more of a social case than anything else. The general conditions of the
      Hospital were precarious. The studied period made possible visualize that the
      treatment given to the patients, as well as the work conditions offered to the
      workers, were distant from the ideal, and that it was part of a national policy,
      characterized by the creation of state macro psychiatric hospitals.

PMID- 14692291
TI  - Primary stability of implants in the posterior maxilla with autogenous bone rings
      harvested in the mandible.

PMID- 14692292
TI  - The knowledge-action gap in diabetes.

PMID- 14692293
TI  - Evidence-based dietary recommendations for patients with type 2 diabetes
      mellitus.
AB  - We review the scientific evidence behind current dietary recommendations for
      patients with type 2 diabetes and examine the effects of various dietary
      interventions on glycemic control, serum lipids, and inflammation in individuals
      with diabetes. Attention is focused on dietary fiber, glycemic index, dietary
      protein, omega-3 fatty acids, chromium, magnesium, and vitamin E. Practical
      dietary recommendations for patients with type 2 diabetes are highlighted.

PMID- 14692294
TI  - Weight loss in diabetes management.
AB  - Type 2 diabetes and obesity are increasing dramatically in the United States and
      in many parts of the world. Both diseases have substantial public health
      consequences in terms of associated morbidity and mortality. In obese individuals
      with diabetes, weight loss can bring several physical and psychological benefits:
      decreased glycosylated hemoglobin and blood pressure, improved lipid levels, and
      elevated sense of well-being. A combination of diet, exercise, and behavioral
      therapy, which are considered components of lifestyle modification, is
      recommended as the first strategy. If an individual is unresponsive to these
      approaches or has comorbidities that are currently compromising his or her
      health, pharmacotherapy and/or surgery may be advised. Weight management
      counseling can prove challenging in diabetes care for the health provider but it
      is vital for the individual with diabetes in terms of preventing or delaying
      further morbidities.

PMID- 14692295
TI  - The role of glycemic index in type 2 diabetes.
AB  - Evidence suggests several benefits to consuming carbohydrates with a low glycemic
      index (GI), Including weight reduction and management of type 2 diabetes
      mellitus. A low-GI diet might alter beta cell function, lipid profile, and
      hypercoagulability.

PMID- 14692296
TI  - Nutrition interventions for prevention of type 2 diabetes and the metabolic
      syndrome.
AB  - Type 2 diabetes is a chronic disease associated with significant morbidity and
      mortality that is increasing in prevalence worldwide. Although our current
      methods for treating type 2 diabetes and its complications have improved,
      prevention of the disease is preferable, Epidemiologic data suggest that most
      cases of type 2 diabetes could be attributed to habits and forms of modifiable
      behavior. Recent evidence from randomized controlled trials has confirmed that
      lifestyle plays a central role in diabetes prevention. However, the optimal
      prevention strategy remains to be determined. This review presents the evidence
      for dietary components that may modify diabetes risk and suggests nutritional
      interventions that may be of benefit in preventing the disease.

PMID- 14692297
TI  - Diabetes control with physical activity and exercise.
AB  - Regular physical activity and exercise are important components in the prevention
      of diabetes. In addition to lowering blood glucose, exercise improves insulin
      action, contributes to weight loss, and reduces several risk factors for
      cardiovascular disease. The association between increased levels of physical
      activity and a reduced occurrence of diabetes' long-term complications suggests
      that regular physical activity has a protective role. This association has been
      shown in the Diabetes Prevention Program. In which physical activity in the form
      of walking for 30 minutes/day on most days of the week was encouraged. Most
      people with diabetes, like people without diabetes, fall to meet national
      physical activity goals. Sedentary lifestyles have been linked to 23% of deaths
      from leading chronic diseases, including heart disease and diabetes. Given the
      epidemic nature of diabetes in the world during the 21st century, diabetes
      management through physical activity and structured exercise should be considered
      an adjunct to diabetes management. While both endurance and resistance exercise
      can improve insulin action and glucose homeostasis, the two forms of exercise
      differ significantly in how they alter muscle metabolism and structure.
      Understanding the beneficial effects of exercise, as well as the mechanisms for
      adopting a physically active lifestyle, is important for the management of
      diabetes mellitus. Despite the well-known benefits of exercise, patient
      education, paired with the implementation and promotion of safe and sustainable
      habits of physical activity for individuals with diabetes, is still inadequate.

PMID- 14692298
TI  - [Results of intraventricular resynchronization in patients with severe cardiac
      failure].
AB  - BACKGROUND: Intraventricular resynchronization with pacemakers is a promising
      therapy for patients with refractory cardiac failure and intraventricular
      conductions delay. However its long term effects are not well known. AIM: To
      report the results of this therapy in patients with cardiac failure. PATIENTS AND
      METHODS: Fourteen patients (11 male), whose mean age was 68 years, with a severe
      and refractory cardiac failure, have been treated in our unit using
      intraventricular resynchronization with pacemakers. Eight had a coronary heart
      disease and six a dilated myocardiopathy. The pacemaker was implanted
      transvenously, with conventional stimulation in atrium and right ventricle. The
      left ventricle was stimulated through an epicardial vein, accessed through the
      coronary sinus. RESULTS: In one patient the high thresholds did not allow a left
      ventricular stimulation. In the other 13 patients, a clinical improvement was
      observed in 11 (85%), that has been sustained for a mean of 8.2 months. The
      ejection fraction improved form 23.5 to 32.4% (p < 0.001), the 6 min walking test
      improved from 347 to 437 m (p = 0.003) and the functional capacity changes from
      3.3 to 2.7 (p < 0.001). Three patients died during follow up. One was the patient
      in whom the stimulation failed and two had a sudden death. No complications of
      the procedure were observed. CONCLUSIONS: In this series, intraventricular
      resynchronization with pacemakers was effective in 11 of 13 patients, improving
      functional capacity and ejection fraction. Sudden death could be avoided adding a
      defibrillator to the pacemaker system.

PMID- 14692299
TI  - [Peptic stricture of the esophagus: long term outcome of conservative treatment].
AB  - BACKGROUND: Endoscopic dilatation of esophageal strictures is a simple and safe
      procedure. AIM: To analyze the long term outcome of conservative treatment for
      esophageal peptic stricture in patients with high surgical risk. PATIENTS AND
      METHODS: Twenty consecutive patients, 13 male, whose mean age was 75.2 years,
      with a peptic stricture of the esophagus and high surgical risk were
      prospectively studied. All were subjected to endoscopic esophageal dilatation and
      treated with continuous medical antireflux therapy thereafter. RESULTS: Only five
      patients complied with antireflux treatment on a regular basis. The remaining 15
      were non compliant or abandoned it. A total of 56 dilatations were done (mean 2.8
      per patient, range 1-6). No complications were observed after the procedure. With
      a mean follow up period of 49 months, the outcome of the conservative treatment
      was classified as excellent or good in all the cases. Eight patients (40%) died
      of causes unrelated to the treatment. Two patients had an organic foreing body
      impactation. This situation was solved endoscopically in both. CONCLUSION: In
      high risk patients, endoscopic dilatation, with or without regular antireflux
      medical treatment is a simple, safe and effective therapy in the management of
      peptic oesophagel stenosis.

PMID- 14692300
TI  - [Association of acute bronchiolitis with climate factors and environmental
      contamination].
AB  - BACKGROUND: Annually, acute bronchiolitis (AB) occurrence peaks during winter and
      is probably associated with air pollution. AIM: To relate the number of
      ambulatory consultations, emergency and hospital admission due to AB with
      climatic factors and air pollution. PATIENTS AND METHODS: Patients of less than 1
      year old with AB that consulted to outpatient clinics, the emergency room or were
      admitted to the Pediatrics ward of the Catholic University Hospital, were
      enrolled. Information about respiratory syncytial virus (RSV) was obtained from
      the Catholic University Medical Investigation Center. Indices of air pollution
      such as particulate matters of less than 10 microns/m3 (PM 10), of less than 2.5
      microns/m3 (PM 2.5), CO, SO3 and O3 were obtained from the Metropolitan
      Environmental Service. Temperature, humidity and precipitations were obtained
      from the Chilean Meteorological Service. RESULTS: Ninety nine consultations in
      out patient clinics and 442 in emergency rooms were collected (55% male, mean age
      4.8 months). One hundred fifty two were admitted (34.4%). Thirty percent of
      children consulting in emergency rooms were younger than 3 months and 43% of them
      were hospitalized. The RSV study was made in 307 patients and 52% were positive.
      There was a higher rate of hospital admissions among RSV positive than RSV
      negative patients (52.5 and 22% respectively, p < 0.001). No association between
      environmental variables or air pollution and the number of consultations was
      observed. Young age and smoking inside the household were the main risk factors
      for hospital admission due to acute bronchiolitis. CONCLUSIONS: Environmental
      variables did not influence the number of cases of acute bronchiolitis. Young age
      and exposure to tobacco smoke were risk factors for hospital admission.

PMID- 14692301
TI  - [Familial transmission of hepatitis C virus infection in Chilean subjects].
AB  - BACKGROUND: Intravenous drug use, sexual promiscuity and a longer cohabitation
      period are considered risk factors for familial transmission of hepatitis C
      virus. The relative importance of this type of transmission is a subject of
      controversy. AIM: To study familial clustering of hepatitis C virus infection and
      its risk factors. MATERIAL AND METHODS: HCV positive patients (91 with chronic
      hepatitis, 88 with cirrhosis, nine with hepatic carcinoma and 29 hemophiliacs)
      were the index cases. HCV antibodies were measured by ELISA and the type of
      relationship with the index case was investigated in 317 family members. RESULTS:
      Positive anti HVC antibodies were detected in 12 of 243 family members of
      patients with chronic liver disease and in none of the family members of patients
      with hemophilia. Of these, five were couples of an index case with a long
      cohabitation period. Ten members had an index case with a severe liver disease
      (three with Child C cirrhosis and seven with liver carcinoma). CONCLUSIONS:
      Family transmission of HCV infection is uncommon in Chile. The association of
      severe liver disease and family transmission could be due to a higher viral load
      as responsible for transmission during the early periods of a long lasting
      disease.

PMID- 14692302
TI  - [Drug induced liver disease: clinical and pathological patterns in 33 cases].
AB  - BACKGROUND: Drug induced liver disease (DILD) is common and of difficult
      diagnosis. AIM: To report the clinical, laboratory and pathological findings in
      33 patients with DILD. PATIENTS AND METHODS: We revised 1,164 liver biopsies and
      57 were selected as suspicious of DILD. In these, the scale proposed by Maria et
      al was applied to assess the possibility of hepatotoxicity reactions and 33 were
      selected. RESULTS: The 33 cases had a mean age of 48 +/- 18 years and 14 were
      male. Forty eight medications were involved, with an average of 1.4 drugs per
      patient. The main drugs were antimicrobials, antineoplastics-immunosuppressives
      and non-steroidal antiinflammatory drugs. The clinical presentations in order of
      frequency were cholestasis, hepatitis, asymptomatic, fulminant hepatitis and
      cirrhosis. The laboratory alterations observed in cases with hepatitis were 20
      fold transaminase and bilirubin elevation. In cholestasis, moderate elevations of
      alkaline phosphatases and gamma glytamyl transferase were observed. Pathology
      showed hepatocellular damage, cholestasis and mixed damage, but also submassive
      necrosis and cirrhosis in one case. CONCLUSIONS: The present study confirms that
      DILD is frequently unpredictable and that it can cause a wide variety of clinical
      and pathological presentations, that can even evolve to chronicity.

PMID- 14692303
TI  - [Is Mapuche ethnicity a risk factor for hip fracture in aged?].
AB  - BACKGROUND: Ethnic factors are involved in the risk for osteoporosis and hip
      fracture. AIM: To assess the effect of Mapuche ethnicity on the risk of hip
      fracture. PATIENTS AND METHODS: A case control study. Cases were subjects over 55
      years of age admitted, during one year, for hip fracture not associated to major
      trauma or tumors. Controls were randomly chosen from other hospital services and
      paired for age with cases. The magnitude of the association between ethnicity and
      hip fracture was expressed as odds ratio in a logistic regression model. RESULTS:
      In the study period, 156 cases with hip fracture were admitted. The proportion of
      subjects with Mapuche origin was significantly lower among cases than controls
      (11.8 and 26.5% respectively, p < 0.001). In the logistic regression model,
      Mapuche ethnicity was associated with hip fracture with an odds radio of 0.14 (p
      = 0.03, 95% CI 0.03-0.8). CONCLUSIONS: In this sample, Mapuche ethnicity is a
      protective factor for hip fracture.

PMID- 14692304
TI  - [Polysomnographic abnormalities in infants with gastroesophageal reflux].
AB  - BACKGROUND: Infant apnea is a common problem that conveys significant burden to
      families and physicians. Its temporal relationship with gastroesophageal reflux
      (GER) is controversial. AIM: To establish whether infants with GER of different
      magnitude have a higher incidence of respiratory events than children without
      GER. PATIENTS AND METHODS: 146 consecutive patients were evaluated with
      polisomnography (PSG) and with an esophageal pH probe. Those infants without GER
      episodes or with an esophageal pH below 4.0 in less than 5% of total sleep time
      were considered as physiologic GER (Group I), between 5-10% as mild GER (Group
      II), and over 10% as severe GER (Group III). These groups were evaluated for
      demographic and polysomnographic characteristics. RESULTS: There were no
      differences in the demographic and global PSG characteristics neither in
      oxymetry, heart rate or electroencephalographic abnormalities. Group III infants
      had a higher percentage of active sleep compared to infants of Group I (p < 0.05)
      and higher incidence of central pauses and apneas compared to infants of Group I
      (p < 0.05). CONCLUSIONS: The presence of severe GER may modify the sleep pattern
      in infants, increasing the percentage of active sleep. The presence of central
      pauses and apneas in infants with severe GER suggest an association between the
      inmaturity of the respiratory centers and the adaptation of the anti-reflux
      mechanisms.

PMID- 14692305
TI  - [Differential effects on serum IGF-1 of tibolone (5 mg/day) vs combined
      continuous estrogen/progestagen in post menopausal women].
AB  - BACKGROUND: Tibolone has estrogenic, androgenic and progestational effects and is
      used in post menopausal women. It apparently has weaker effects on endometrial
      proliferation and mammary stimulation than conventional hormone replacement
      therapy. AIM: To compare the metabolic effects of tibolone (5 mg/day) and
      continuous combined conjugated estrogens/medroxyprogesterone acetate in
      postmenopausal women. PATIENTS AND METHODS: Postmenopausal women, aged 45 to 60
      years old, receiving estradiol valerate and medroxyprogesterone were included in
      the study. After a two months wash out period, in a double blind fashion, they
      were randomly assigned to oral tibolone 5 mg/day or equine conjugated estrogens
      0.625 mg + medroxiprogesterone acetate 2.5 mg/day (ECE/MPA). At baseline, 30 and
      45 days of treatment, fasting serum osteocalcin, somatomedin C (IGF-1, insulin
      like growth factor 1), growth hormone (GH), and follicle stimulating hormone and
      first morning urine calcium and creatinine were measured. RESULTS: Thirty women
      were studied. There was more than 50% fall in urine calcium with either tibolone
      or ECE/MPA, while fasting GH or osteocalcin did not show significant changes.
      Serum IGF-1 increased significantly with tibolone at basal, 30 (+109%) and 45
      days of treatment and did not change in the ECE/MPA group. CONCLUSIONS: Tibolone
      (5 mg/day) and ECE/MPA induced a similar reduction in urinary calcium. Tibolone
      increased serum IGF-1 levels. This may be due to undetected increment of overall
      GH secretion or to a specific action or IGF-1 generation from the liver and
      appears to be a novel differential effect of tibolone.

PMID- 14692306
TI  - [Effectiveness of infliximab in patients with inflammatory arthritis refractory
      to conventional treatment].
AB  - BACKGROUND: Tumor necrosis factor antagonists are useful in the treatment of
      several chronic inflammatory immune mediated diseases. AIM: To assess the effects
      of infliximab in 21 patients with inflammatory arthropaties, refractary to
      conventional treatment. PATIENTS AND METHODS: Eleven patients with rheumatoid
      arthritis, seven with psoriatic arthritis and three with spondyloarthritis were
      treated. The mean duration of the diseases was 10 years. Infliximab was
      administered intravenously in a dose of 3 mg/kg body weight. A median of 6 doses
      in 8 months was administered. Effectiveness was assessed in 19 patients that
      received three or more doses. RESULTS: Infliximab was effective in 16 patients
      (10 with rheumatoid arthritis, four with psoriasis and two with
      spondyloarthritis) and ineffective in three. In responsive patients, a reduction
      in the number of inflammed joints and morning stiffness and an improvement in
      functional capacity was observed. Fifteen of the 16 patients perceived an
      improvement in their health status. This answer was concordant with concomitant
      medical evaluation in 15. Patients that maintained the treatment felt very well,
      well or regular, whereas five of six patients that discontinued the treatment
      felt ill. Thirteen patients had adverse effects. Treatment was discontinued in
      two patients due to drug induced lupus, allergy in 2, hypertension in one, high
      costs in three and lack of response in three. CONCLUSIONS: Infliximab reduced
      arthritic activity in 16 of 19 patients with severe treatment refractary
      arthritis.

PMID- 14692307
TI  - [Prevalence of congenital malformations and low weight at birth among teenage
      mothers].
AB  - BACKGROUND: In Chile, 14 to 16% of births occur in teenage mothers. These mothers
      apparently have a higher frequency of premature labor, low birth weight and
      congenital malformations. AIM: To assess the frequency of prematurity, congenital
      malformations and weight at birth among the offspring of adolescent mothers.
      PATIENTS AND METHODS: The births occurred in a hospital between 1982 and 2001,
      were analyzed using the Latin American Collaborative Study for Congenital
      Malformations (ECLAMC) data base. Mothers were classified as teenagers when their
      age ranged between 10 and 19 years old and older when their age was over 20 years
      old. All women were subdivided as cases and controls. RESULTS: The sample was
      formed by 894 teenage and 806 older mothers. Seven percent of both teenage and
      older mothers had offspring with one or more malformations. The incidence of low
      birth weight newborns and of prematurity was also similar in both groups of
      mothers. CONCLUSIONS: In this sample, offspring of teenage mothers do not have a
      higher frequency of malformations, low birth weight or prematurity.

PMID- 14692308
TI  - [Hantavirus cardiopulmonary syndrome: utility of the PICCO(Pulse contour cardiac
      output) system for monitoring].
AB  - We report a 68 years old man, farmer from the metropolitan region, admitted with
      a Hantavirus Cardiopulmonary Syndrome. The diagnosis was made using serologic
      test and was later confirmed by the Public Health Institute. He evolved to an
      early multiple organ failure, requiring high concentrations of oxygen and
      invasive ventilatory assistance, vasopressor drugs and renal replacement therapy.
      Swan Ganz and PiCCO were used simultaneously for hemodynamic monitoring.
      Treatment consisted in global support therapy, antimicrobial therapy and systemic
      corticosteroids. Intrathoracic blood volume was a more reliable parameter than
      pulmonary capillary wedge pressure for the assessment of preload. As expected in
      situations of increased vascular permeability, there was an increase in
      extravascular lung water. There was a good correlation between extravascular lung
      water and oxygenation parameters (PaO2/FiO2 and oxygenation index). PiCCO system
      may become a helpful tool in the management of patients with Hantavirus
      Cardiopulmonary Syndrome.

PMID- 14692309
TI  - [Familial amyloidotic polyneuropathy type I].
AB  - Familial amyloidotic polyneuropathy type I is an autosomal dominant inherited
      disorder characterized by progressive peripheral and autonomic neuropathy,
      associated with neural and systemic amyloid deposits. The abnormality usually
      lies in the transthyretin (TTR) gene. We report a 25 years old man with 18 months
      history of dysesthesias and pain in the toes, abnormal micturition and sexual
      dysfunction. Neurophysiologically studies disclosed a sensory-motor axonal
      polyneuropathy. Autonomic tests showed sympathetic and parasympathetic
      involvement. An electron micrograph of sural nerve revealed amyloid fibrils in
      the endoneurium. His mother died after a clinical history suggestive, in
      retrospect, of familial amyloidotic polyneuropathy type I. The clinical and
      genetic analysis of this cause of polyneuropathy are discussed.

PMID- 14692310
TI  - [Brown tumors in multiple locations: manifestation of severe renal
      osteodystrophy. Case report].
AB  - We report a 25 years old woman with a four years history of end stage renal
      disease on hemodialysis. During the last two years of follow up, multiple tender
      nodules appeared in the left clavicle and ribs. These were diagnosed as brown
      tumors, secondary to osteitis fibrosa cystica, in the context of a secondary
      hyperparathyroidism. A subtotal parathyroidectomy was performed and a homologous
      parathyroid implant was done in the right forearm. The pathological study of the
      surgical pieces confirmed the presence of the brown tumors and parathyroid
      hyperplasia. Nine months after surgery, parathormone levels and brown tumor
      calcifications decreased significantly and bone mineral density increased by 20%.

PMID- 14692311
TI  - [Admission to medical school of Bachelors of Science: experience of 5 years].
AB  - BACKGROUND: In industrialized countries, most students are admitted to medical
      schools after obtaining a Bachelor degree. In 1993, the Catholic University of
      Chile instituted a program to obtain a Bachelor degree. These students can apply
      to Medical School. AIM: To compare the academic achievement of students admitted
      to medical school directly from high school or after obtaining a Bachelor degree.
      SUBJECTS AND METHODS: Cohorts of medical students coming directly from high
      school or after obtaining a Bachelor of Sciences degree, between 1997 and 2001,
      were studied. Social and demographic background, scores of the Academic Achieving
      test and grades obtained during high school and in medical school, were compared
      in both groups. RESULTS: The distribution of gender and the region of origin were
      similar in both groups of students. Thirty two percent of bachelors and 18% of
      high school students admitted to medical school, came from public schools (p =
      0.014). The Academic Achieving test score was 727 +/- 27 and 764 +/- 11 points in
      bachelor and high school students respectively (< 0.001). However the mean grades
      in Medical School were similar in both groups of students. CONCLUSIONS: Bachelor
      degrees are a good opportunity for students, that must be considered by Medical
      Schools in their admission systems.

PMID- 14692312
TI  - [Attention deficit hyperactivity disorder in adults].
AB  - The attention deficit hyperactivity disorder (ADHD) is the most common diagnosis
      in child psychiatry, and persists very often in adulthood. These patients have
      poor lifestyles, especially in affective, work and social areas. Although
      patients with ADHD have a high rate of comorbidity (e.g. drug and alcohol abuse,
      depressive and anxiety disorders), this diagnosis is missed by the general
      physician, deferring its identification and opportune treatment. This article is
      a review about this disorder and gives tools for its recognition and derivation.

PMID- 14692313
TI  - [Questions formulation in Evidence-Based Medicine].

PMID- 14692314
TI  - [Scientific ethics of gene therapy for individuals. The urgency for DNA gene
      surgery].
AB  - Gene therapy for individuals is mainly directed to somatic or germ cells. The
      present technology aims to insert a DNA segment in the recipient cells. This
      therapy is useful in Mendelian recessive diseases. There is an ethical moratorium
      to perform insertion gene therapy in germ cells, because this procedure increases
      the human genome. Somatic cell gene therapy cures individuals but increases the
      gene frequency of genetic diseases in the population. This occurs because the
      descendants of the cured patient should carry his or her "ill" genes. We denots
      by "DNA gene surgery" the procedure that replaces "ill" nucleotide(s) by healthy
      one(s) conserving the genome size and the gene context of expression and
      regulation. Several procedures for gene surgery have been applied to cells and
      animals. Those based on DNA repair as Chimeric RNA/DNA, one stranded
      oligonucleotides and tristranded DNA. Those based on DNA recombination with oligo
      DNA or one stranded DNA, and transposable DNA segments. Gene surgery can be
      applied to germ cell gene therapy without ethical contraindications. It can cure
      Mendelian dominant diseases and it can be applied to heterozygotes. It preserves
      the regulation and expression gene context. If a technical safe procedure is
      available, the entire mankind could be treated and cured of all the Mendelian
      diseases, in one generation. Susceptibilities for all diseases could also be
      treated. The moratorium for research on germ cell gene therapy by gene surgery
      should be interrupted. Safe gene surgery is a moral imperative for gene therapy
      of patients and their descendants, for the treatment of dominant genetic diseases
      and for heterozygous carriers of recessive disorders.

PMID- 14692315
TI  - [Control of professional ethics].

PMID- 14692316
TI  - [Plant growth analysis of Bupleurum chinense].
AB  - OBJECTIVE: To learn the development characteristics of Bupleurum chinense DC. for
      the cultivation fundament. METHOD: Mature and intact plant samples of different
      growing periods are studied by the method of plant growth analysis. RESULTS: The
      plant organs are composed of root, root crown, stalk, basal leaves, stem leaves,
      branches and leaves, apical and lateral inflorescences. Dry substance in the
      branches of the first and second level was 93.8% of that in all branches. Though
      the branches of third or fourth level were relatively weak, their amount was
      large. The root-shoot ratio with the value 0.19 was especially low. Lateral
      inflorescences of third or fourth level were found commonly in the population,
      but the first and second ones were the majors part. About 38.1% dry substance was
      used for the development of propagation organ. The length of main root was only
      17.2 cm, its weight was nearly same as that in the lateral roots. CONCLUSION:
      Short cultivated history of B. chinense are still maintained some significant
      wild characteristics, so they don't accord with the demand of the objective
      gathering in the root. It may be resolved with artifical regulation and breeding.

PMID- 14692317
TI  - [The dual-index sequence analytical method of common peak ratio and variant ratio
      for analysing UV fingerprint spectra of Radix Glycyrrhizae].
AB  - OBJECTIVE: To set up the dual-index sequence analytical method for UV fingerprint
      spectra (FPS) in which the dual indices are common peak ratio and variant ration.
      METHODS: Three kinds of solvents chloroform, alcohol and water were used to
      extract different polarity components from Radix Glycyrrhizae, and then the UV
      FPS of the components were measured, which were applied to distinguish the
      samples. RESULTS: This method is effective for distinguishing Radix Glycyrrhizae
      from inner Mongolina, Gansu and Xinjiang. CONCLUSION: The UV-FPS dual-index
      sequence analytical method is feasible.

PMID- 14692318
TI  - [Determination of formononetin and calycasin from Radix Hedysari by HPLC].
AB  - OBJECTIVE: To establish a method of RP-HPLC for the determination of formonontin
      and calycasin from Radix Hedysari. METHODS: High-performance-liquid
      chromatography (HPLC) on a Kromasil ODS column (5 microns, 4.6 mm x 250 mm) with
      water-methanol gradient elution, at column temperature of 25 degrees C, flow-rate
      of 1.0 ml/min and wavelength at 254 nm. RESULT: Linear ranges of formonontin and
      calycasin were 2.325 x 10(-3)-4.650 x 10(-2) micrograms and 2.350 x 10(-3)-4.700
      x 10(-2) micrograms respectively. The average recoveries were 96.53% and 98.34%
      respectively, and relative standard deviations were 1.63% and 2.00%. CONCLUSION:
      The method was simple, reliable, accurate and practical.

PMID- 14692319
TI  - [Studies on the chemical constituents of Ampelopsis humulifolia var. heterophylla
      (Thunb.) K. Koch].
AB  - OBJECTIVE: To study the chemical constituents from Ampelopsis humulifolia var.
      heterophylla (Thunb.) K. Koch. METHODS: Chromatography and spectroscopic analysis
      were employed to isolate and elucidate the chemical constituents in the plant.
      RESULTS: Six compounds were isolated and elucidated as lupeol, beta-stiosterol,
      daucosterol, ethyl gallate, gallic acid and catechin. CONCLUSION: The six
      compounds were isolated from this plant for the first time.

PMID- 14692320
TI  - [Time-effect and dose-effect relationships study on the effect of benefiting-bone
      capsule on osteoblasts proliferation].
AB  - OBJECTIVE: To investigate the effect of rats sera containing Benefiting-bone
      Capsule (BBC) on the cell proliferation of skull osteoblast in neonatal SD rats.
      METHODS: Forty female SD rats, aged 12 months, were randomly divided into 4
      groups including N.S. group, low dosage, middle dosage and high dosage BBC group,
      the sera were obtained at different times. MTT method was used to determine the
      effect of BBC on osteoblasts proliferation. RESULTS: The MTT value reached its
      highest point 1.5 hours after oral administration (P < 0.05). MTT of high dosage
      BBC met the maximum value with the concentration of 25% (P < 0.05). CONCLUSIONS:
      The rats sera containing BBC can promote proliferation of osteoblast.

PMID- 14692321
TI  - [The mechanism of Radix Salviae Miltiorrhizae Injection on the inhibition of
      smooth muscle cell proliferation induced by H2O2].
AB  - OBJECTIVE: To observe the effect of Radix Salviae Miltiorrhizae Injection (RSMI)
      on proliferating cell nuclear angiten (PCNA), NF-kappa B and cell cycle phase of
      vascular smooth muscle cell(VSMC) induced by H2O2 in vitro. METHODS: H2O2 was
      added to the medium for culturing rat aortic VSMC as extraneous reactive oxygen
      species (ROS). The protein expression of PCNA and NF-kappa B was examined with
      immunocytochemical technique in VSMC, and cell cycle phase analysis was used to
      detect proliferation of VSMC. RESULTS: The result showed that the protein
      expression of PCNA and NF-kappa B became stonger, the ratio of S phase cells
      became higher in H2O2 group. RSMI could increase the percentage of the cells in
      G0/G1 phase, decrease the percentage of the cells in S phase and obviously
      inhibit the expression of PCNA and NF-kappa B proteins. CONCLUSIONS: The
      expression of PCNA and NF-kappa B was inhibited and the transition from G0 phase
      to S phase was blocked, which may be one of the key mechanism of RSMI on the
      inhibition of VSMC proliferation induced by H2O2.

PMID- 14692322
TI  - [Effects of beta-asaron on gene expression in mouse brain].
AB  - OBJECTIVE: To observe effects of beta-asaron on gene expression in BALB/c mouse
      brain by gene chip. METHODS: The mRNA of mouse brain samples of experiment group
      and control group was markered with cy5, cy3 fluorescence separately, and
      hybridized with 4000 genes on MGEC-40S gene chip after mix. Fluorescence
      intensity was scanned with Genepix 400 B scanner and analysed with Genepix Pro3.0
      soft. RESULTS: Among 4000 genes, there are 15 genes with difference expression
      (the ratio > 1.9 or < 0.59) in two groups. In beta-asaron group, 4 genes
      expression raised relating to ion channels, substance transform through membrane,
      calcium-dependent protein kinase regulation, apoptosis, 11 genes expression
      declined relating to excitatory neurotransmitter metabolism in the CNS, T
      lymphocyte tend, genes expression regulation and drug metabolism. CONCLUSION:
      beta-asaron has effects on multi-target genes in mouse brain.

PMID- 14692323
TI  - [Effects of Semen Sojae Preparatum on lipid metabolism in ovariectomized rat].
AB  - OBJECTIVE: To investigate the antiatherosclerotic effect of Semen Sojae
      Preparatum (SSP) and its mechanism. METHODS: 48 rats were randomly divided into
      sham operation group (sham), ovariectomized group (OVX) and three doses of OVX +
      SSP groups. SSP was given to OVX + SSP groups 2 weeks after ovariectomy. The
      levels of serum lipids and lipid peroxidation were detected after 12 weeks
      treatment. RESULTS: SSP lowered serum oxidized-low density lipoprotein
      cholesterol (OX-LDL, P < 0.01), triglyceride (TG, P < 0.01) and malondialdehyde
      (MDA, P < 0.05 or P < 0.01), and enhanced serum high density lipoprotein
      cholesterol (HDL-c, P < 0.05 or P < 0.01), polipoprotein A I (apo-AI, P < 0.01)
      and superoxide dismutase (SOD, P < 0.01) activity. CONCLUSION: SSP had effects on
      regulating lipid and antioxidation. Therefore, it might inhibit atherosclerosis
      in ovariectomy rats.

PMID- 14692324
TI  - [Study on the inhibition of alpha-glucosidase by soyasaponins].
AB  - OBJECTIVE: To study the inhibitory effects of soyasaponins on alpha-glucosidase
      (EC3.2.1.20). METHODS: Soyasaponins were isolated by ODS column chromatography
      and high-performance liquid chromatography (HPLC) from hypocotyls of soybean. The
      inhibitory activities of each component of soyasaponins against alpha-glucosidase
      were tested by colorimetric method. RESULTS: Soyasaponins showed potent
      inhibitory activities against alpha-glucosidase. Group B, group E and DDMP (2,3
      dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one) saponins showed stronger potency,
      which were non-competitive inhibitors of alpha-glucosidase with IC50 values of 10
      40 mumol/L. While group A saponins showed a little lower potency with IC50 values
      of about 2 mmol/L. CONCLUSION: The results suggest soyasaponins, which exhibit
      inhibitory effects on alpha-glucosidase, seem physiologically useful for
      suppressing postprandial hyperglycemia in patients with diabetes mellitus.

PMID- 14692325
TI  - [Study on effects of Erigeron breviscapus extract on anticoagulation].
AB  - OBJECTIVE: To study the effect of Erigeron breviscapus extract on
      anticoagulation. METHOD: Coagulation time (CT), prothrombin time (PT), platelet
      factor III (PF3) and euglobulin lysis time (ELT) have been used to evaluate the
      anticoagulation activities of Erigeron breviscapus extract. RESULT: Erigeron
      breviscapus extract significantly delayed CT and PT, inhibited the activity of
      PF3, and decreased ELT. CONCLUSION: Erigeron breviscapus extract plays an role in
      anticoagulation by inhibiting PF3 and prothrombin V. It can also enhance the
      activity of fibrimolysis.

PMID- 14692326
TI  - [Influence of decoction methods and compatibility on content of cinnamaldehyde in
      Mahuang decoction].
AB  - OBJECTIVE: To develop a GC-MS method for the determination of cinnamaldehyde and
      study on the influence of decoction methods and compatibility on the contents of
      cinnamaldehyde in Mahuang decoction. METHODS: Gas chromatography-mass
      spectrometry (GC-MS) was used. Chromatography/mass spectrometric conditions were:
      capillary column DB-17 (30 m x 0.5 mm, 0.25 micron), helium as carrier gas, non
      split injection, column primary temperature 120 degrees C, 120 degrees C 8
      degrees C/min-->250 degrees C, with 1.0 ml/min runoff, and injection volume 1
      microliter. The results were analyzed by one-way ANOVA (SPSS). RESULTS: The
      calibration curves were linear in the range from 0.0136 mg/ml to 0.136 mg/ml (r =
      0.9999). The RSD of precison, stability and reproducibilities were 1.02% (n = 6),
      2.57% in 24 h and 4.20%, respectively. The cinnamaldehyde content in the blended
      Mahuangtang decoction (BMHD) was significantly lower than the one in the
      separated and mixtured decoction and Ramulus cinnamomi decoction (P < 0.05). The
      separated and mixtured decoction was higher than Ramulus cinnamomi decoction (P >
      0.05). CONCLUSION: The main influencing factor of the cinnamaldehyde content was
      the compatibility. This method is precise and reliable to study cinnamaldehyde in
      Mahuang Decoction.

PMID- 14692327
TI  - [Selection of optimal extraction process for huolisu capsule by orthogonal
      design].
AB  - OBJECTIVE: To find out the optimal extraction process for Huolisu capsule.
      METHOD: The extraction process was studied by orthogonal design with yield of the
      extracted ginsenoside Re and anthraquinone content determined by RP-HPLC as
      indexes. RESULT: The result showed that the optimal extraction process was 50%
      alcohol, 8 times the amount of herbs, refluxing for 2 times, each time 2 hours.

PMID- 14692328
TI  - [The effect of yang xue qing nao granule on chronic cerebral ischemia].
AB  - OBJECTIVE: To study the effect of Yang Xue Qing Nao Granule (YXQNG) on the
      chronic cerebral ischemia (CCI). METHODS: 80 cases with CCI were divided randomly
      into treatment group (43 cases) and control group (37 cases). Each group was
      disposed with intravenous drops of energy mixture. Besides, treatment group was
      prescribed with YXQNG, control group received nimedipine plates. The whole
      therapeutic process of each group was 30 days. The vertibrobasal artery systolic
      end maximum flow rate (VBASEMFR) and blood rheology (BR) were tested before and
      after treatment. RESULTS: The total efficiency of treatment group was 90.70% (P <
      0.05). The effect of treatment group on lowering blood viscosity and enhancing
      the cerebral blood flow rate was better than that of control group (P < 0.05).
      CONCLUSION: YXQNG can effectively treat CCI and improve the life quality of
      patients.

PMID- 14692329
TI  - Stress and anxiety after 9/11: a prospective study.

PMID- 14692330
TI  - Medical disasters: are we really prepared? An analysis of the station fire.

PMID- 14692331
TI  - The station nightclub fire and disaster preparedness in Rhode Island.

PMID- 14692332
TI  - One response to the threat of bioterror: smallpox vaccination.

PMID- 14692333
TI  - Rhode Island emergency physicians and the disaster relief effort in Chuuk,
      Micronesia.

PMID- 14692334
TI  - On-site medical care during the September 11th WTC terrorist attack rescue and
      recovery effort and the National Disaster Medical System (NDMS).

PMID- 14692335
TI  - The case of the wintertime fever and chills: a mosquito mystery.

PMID- 14692336
TI  - Deaths and injuries from structure fires in Rhode Island.

PMID- 14692337
TI  - Hydrogen sulfide exposure on Rhode Island's shoreline.

PMID- 14692338
TI  - The forcible treatment of criminal defendants.

PMID- 14692339
TI  - Effect of endocrine disrupters on immune responses in vivo.
AB  - In previous papers we reported that endocrine disrupters (EDs) such as 4,4'
      isopropylidene diphenol (Bisphenol A: BPA), bis(2-ethylhexyl) phthalate (EHP) and
      p-nonylphenol (NP) stimulated proliferative responses and cytokine productions of
      murine spleen cells and thymus cells in vitro. In this paper we report our
      studies on the effect of EDs on immune responses in vivo. EDs (10(-5) M) such as
      BPA, EHP and NP were administered to mice by free drinking for 6 weeks and their
      immune responses were studied both in vitro and in vivo. EDs did not affect the
      body weight of the mice, spleen and thymus cell numbers, and serum immunogloburin
      concentration. The proliferative responses of spleen cells cultured in vitro were
      not changed by EDs-administration. However, the proliferative responses of thymus
      cells from EDs-treated mice were enhanced. Furthermore, the immunization of EDs
      treated mice with protein antigens resulted in the enhanced production of
      antibody. These results suggest that EDs have immunomodulating activities in
      vivo.

PMID- 14692340
TI  - Effects of screen size and task difficulty on vigilance performance of older
      adults.
AB  - This paper describes an experiment to elucidate the effects of aging on vigilance
      performance with VDTs. In addition, the experiment was undertaken to evaluate
      whether the aging effects are affected by the degree of task difficulty and by
      the screen size of the VDTs. Forty healthy male volunteers were studied in two
      age groups of 20 participants. In the experiment, the participants were required
      to perform vigilance tasks, which were presented either on a conventional 17-inch
      display or a large-sized 110-inch display. The 60-minute task period was divided
      into three 20-minute phases assigning the tasks with two scenarios of different
      degrees of difficulty. Performance was measured using reaction time for detection
      and number of detection errors. The results pointed out three effects: (1) the
      performance of the vigilance tasks deteriorated more markedly among the older
      adults than among the younger adults; (2) the between-screen differences on the
      vigilance performance were significant for the older adults, but not for the
      younger adults; (3) the effect of screen size was amplified by increasing the
      degree of task difficulty. These data indicate that screen size and task
      difficulty have an effect on vigilance performance with VDTs of older adult.

PMID- 14692341
TI  - Immunological and molecular mechanisms of photoallergic contact dermatitis.
AB  - Photocontact dermatitis is one of the major occupational skin diseases and an
      undesirable adverse effect produced by chemicals and drugs in our environment.
      This dermatitis is caused by skin application of photosensitive agents plus
      ultraviolet light irradiation. There exist both primary irritant and allergic
      mechanisms in this dermatosis. While the former is induced by the phototoxic
      reactions, the latter allergic type is mediated by Langerhans cells, T cells,
      various cytokines and chemokines, and thus occurs via a well-orchestrated and
      well-elucidated immunological mechanism. The photoallergic type has a higher
      incidence and more severe skin eruptions than the primary irritation.
      Photoconjugation of epidermal cells with a photohaptenic halogenated chemical is
      the initial step, and Langerhans cells serve as antigen-presenting cells.
      Causative photohaptens are bound to MHC class II molecules/self peptide on
      Langerhans cells upon exposure to UVA. The photomodified Langerhans cells
      sensitize and elicit antigen-specific T cells that mediate photoallergy. Thus,
      this photoallergy is induced by well-orchestrated photochemical and immunological
      mechanisms.

PMID- 14692342
TI  - [Low methane concentration in the breath of Japanese].
AB  - A survey of breath methane excretion in Japanese is reported in this paper. The
      prevalence of methane excretion was 15% in 231 Japanese subjects, which was
      significantly lower than the range 33-60% reported in Canada and the USA. The
      prevalence of methane excretion was only 3% in males between the ages of 18-29
      years old. However, it increased with age, and both males and females within the
      ages of 50-59 years old reached to almost the same value of 25-27%. When both
      parents were methane producers, 67% of their children were also methane
      producers. On the other hand, only 6% of the children were methane producers when
      both parents were methane non-producers. The prevalence of methane excretion was
      55% in Caucasians who have lived in Japan for four years or longer. This is the
      same level reported in Canada and the USA. The effect of familial component and
      ethnic origin suggested that breath methane excretion is strongly affected by
      genetic factors.

PMID- 14692343
TI  - [Vasculogenesis and angiogenesis].
AB  - Vasculogenesis is defined as a neovascularization manner by which endothelial
      progenitor cells are successively incorporated into the growing capillaries,
      whereas angiogenesis is another neovascularization manner which includes mitotic
      proliferations of endothelial cells of the preexisting capillaries and their
      migration to the vascular tips forming so called "vascular sprouts" or
      "endothelial buds". Although angiogenesis had been considered to be more
      prevalent during organogenesis as well as during a wound healing process of adult
      mammals, recent findings that endothelial progenitor cells were isolated from
      human peripheral blood and incorporated into sites of active neovascularization
      have led many researchers to recognize the significance of vasculogenesis in a
      phenomenon of neovascularization. This paper mainly deals with the history of
      morphological approaches to clarify the crucial roles of vasculogenesis during
      organogenesis and a wound healing process.

PMID- 14692344
TI  - [Hyperbaric oxygen therapy for neurologic emergency and neurosurgical diseases: a
      systematic review of the literature].
AB  - I have reviewed reports concerning neurologic emergency and neurosurgical
      diseases adjunctively treated with hyperbaric oxygen (HBO) therapy. Some clinical
      studies indicate the favorable effects of HBO therapy on the events at an ultra
      acute stage of brain ischemia. This therapy has been used in the treatments of
      other neurologic emergency diseases, such as brain and spinal injury, carbon
      monoxide intoxication, decompression illness involving the central nervous system
      and so on. Some reports clarify that patients with malignant gliomas have a
      prolonged survival by radiotherapy after HBO therapy. In addition, I have applied
      HBO preexposure to radiosurgical treatments for recurrent and brain stem gliomas.
      HBO therapy enhances the effects of some chemotherapeutic agents such as platinum
      drugs and nitrosoureas. Especially, the therapeutic effect of carboplatin, one of
      platinums, is improved by HBO therapy in recurrent malignant tumors. Although
      radiation-induced brain injury is the most serious problem after radiosurgery,
      HBO therapy controls this condition and its progression. Wound infection after
      intracranial or spinal surgery is well controlled by anti-infectious drugs
      combined with HBO therapy. Now HBO therapy is an important therapeutic option in
      the fields of neurologic emergency and neurosurgery. However, high-quality
      randomized controlled trials that evaluate the short- and long-term risks and
      benefits of HBO therapy are necessary to better inform clinical decisions.

PMID- 14692345
TI  - [Antimicrobial activity of hinokitiol against Legionella pneumophila].
AB  - Antimicrobial activity of hinokitiol (beta-thujaplicin), which is a major
      component of the essential oil of Chamaecyparis obtuse, against Legionella
      pneumophila was investigated experimentally. The quantitative antibacterial assay
      of hinokitiol was carried out by the disk-diffusion method. The test
      concentrations of hinokitiol were 0.39 to 25.0 micrograms/disk, and the lowest
      concentrations of hinokitiol that showed growth inhibition against L. pneumophila
      were 1.56 micrograms/disk on B-SYE agar and 0.39 microgram/disk on B-SYE agar
      without iron.

PMID- 14692346
TI  - [The clinical effect of lateral wedge on hemiplegic weight bearing].
AB  - The purpose of this study was to investigate the influence of the lateral wedge
      on asymmetrical weight bearing and posture in hemiplegic gait. The subjects were
      2-female and 4-male moderate stroke patients, average age 54 +/- 6 yr. The time
      from onset was 127 +/- 69.7 days. A 7 mm-thick wedged insole was applied to the
      affected side for a week. Before and after that, the vertical ground reaction
      force, single supporting period and side movement of the trunk were recorded
      during walking. As a result, we found that the vertical ground reaction ratio and
      single supporting period ratio of the affected side (affected/unaffected) were
      significantly increased (P < 0.05), and also that the lateral sway of the trunk
      was remarkably decreased (P < 0.05). Our results indicate that the application of
      the lateral wedge for a week improved asymmetrical weight bearing and gait
      ability in moderate hemiplegic patients. Also we believe that a randomly sampled
      comparison study should be performed in the near future.

PMID- 14692347
TI  - [Present and expected role of the nurse in Japanese hemophilia care: result of a
      questionnaire survey of hemophiliacs and their families].
AB  - Since 1970, many hemophilia centers have been opened in the United States and
      Western Europe. In these centers, nurse coordinators (NCs) play an important role
      as key persons in improving the QOL of hemophiliacs with a variety of problems.
      On the other hand, NCs have not been stationed in most Japanese hemophilia
      centers, although many doctors and nurses in charge of hemophilia care desire
      that NCs participate in hemophilia treatment. Therefore, a survey of hemophiliacs
      and their families was conducted to clarify the role of the nurse in Japanese
      hemophilia care. The results obtained from the analysis of responses concerning
      393 patients indicated that about two thirds of the respondents had never
      consulted with nurses in regard to their disease. Although the total number of
      items of care and support which were offered by nurses to the patients was 739,
      the total number of these items which were expected to be offered from nurses to
      the patients was 1078. These results indicate that the introduction of NCs is
      necessary for hemophilia care in Japan.

PMID- 14692348
TI  - [Report from the 23rd UOEH meeting of gastrointestinal image diagnosis].

PMID- 14692349
TI  - [The thyroid gland in women during the reproductive age].
AB  - OBJECTIVE: To find out thyroid volume and its functional status in women in
      reproductive age as well as possible correlation between thyroid size and
      functional status and age and residential location of women. DESIGN: Project can
      be characterized as an epidemiological study and consists of three separate
      observations. SETTING: 1st Internal Clinic, UPJS, Kosice, Medical Faculty,
      Slovakia. METHODS: 347 women from different regions of Eastern Slovakia (160 aged
      20-29 and 187 aged 30-40) were measured thyroid volume via ultrasonography and
      thyroid functional status by RIA TSH and anti TPO examinations. Urinary iodine
      was examined in 70 cases. In this part of the study correlation between thyroid
      size and functional status and age and residential location of women were
      determined. Four days after delivery thyroid volume in 99 women was measured. The
      volume was correlated with the number of previous pregnancies. Thyroid volume was
      correlated with residential location and number of pregnancies of 77 women that
      had not delivered in the previous year. RESULTS: Women aged 20-29 years had
      thyroid volume smaller than women aged 30-40 (8.78 ml/10.66 ml; p < 0.01). The
      size of thyroid gland was not only affected by age but also by residential
      location. The largest thyroid glands and increased level of anti TPO antibodies
      in both age groups were found in women from agricultural regions and regions
      close to chemical factory. The women with anti TPO antibodies had increased level
      of TSH as well as more frequently changed echogenity of thyroid gland. Median of
      urinary iodine was 13.2 micrograms/dl in both age groups and indicated sufficient
      iodine intake in the observed area. The volume of thyroid gland four days after
      delivery did not exceed 22 ml in 89.9% of cases. Significant difference in size
      of thyroid gland depending on number of previous deliveries was not only observed
      in women 4 days after delivery but also in those that had not delivered during
      previous year. The largest volumes were measured in secundiparous mothers.
      CONCLUSION: Polluted environment affects the size and functional status of
      thyroid gland. Environment can via this negative impact on thyroid gland
      influence fertility, pregnancy and fetus development in women in reproductive
      age.

PMID- 14692350
TI  - [Vaginal delivery in primiparas and anal incontinence].
AB  - OBJECTIVE: An investigation of incidence and degree of anal incontinence after
      vaginal delivery among primiparas and characterizing of the risk factors. DESIGN:
      Prospective observational study. SETTING: Department of Gynecology and
      Obstetrics, Charles University and Faculty Hospital Pilsen. METHODS: 346
      primiparas after consecutive vaginal delivery between May 2000 and February 2001
      were included. All delivered in lithotomy position. Questionnaires were sent few
      days after delivery and then two and 6-9 months later. Analysis of the returned
      questionnaires. 28 obstetric parameters assessed. RESULTS: 46.5% women responded.
      23 women registered leakage of flatus before delivery. Two months postpartum one
      (0.6%) patient reported fecal incontinence and 22 (14.3%) flatus incontinence de
      novo or impaired already present incontinence. 6-9 months after delivery the same
      patient (0.6%) reported fecal incontinence and 16 women (10.4%) incontinence of
      flatus. Ten of them felt impaired quality of life. Anal incontinence gradually
      improved during the time (in 76%). Risk factors of developing (worsening) of anal
      incontinence were antenatal anal incontinence (in two months period) and women
      weight (or BMI) measured at 6-9 months after birth. None of nine patients after
      forceps delivery (Breus traction forceps) which responded reported signs of anal
      incontinence. Neither the range of episiotomy nor the length of perineum had any
      relation to the development of anal incontinence. However episiotomy has been
      shown to be a protective factor of 3rd degree tear in primiparas (RR 0.24). Third
      degree tear was diagnosed in seven cases (2%), three out of 6 women reported anal
      incontinence postpartum. CONCLUSION: This study shows relatively frequent
      development of flatus incontinence after vaginal delivery in primiparas. These
      symptoms usually improve within the time. Only minimum of women after vaginal
      delivery suffers of fecal incontinence. 42% of women with anal incontinence feel
      impaired quality of life. At the first postpartum check every woman should be
      asked, whether she has any symptoms of anal or urine incontinence or impaired
      sexual health. If positive the answer, the woman should get information where to
      find a help.

PMID- 14692351
TI  - [Occurrence of congenital developmental defects in the Czech Republic in 2001].
AB  - OBJECTIVE: Analysis of incidences of congenital malformations (CM) in prenatal
      and postnatal diagnostics in the Czech Republic in 2001 and a comparison to the
      years 1994-2000. DESIGN: A retrospective demographic-epidemiological study.
      SETTING: Institute for Care of Mother and Child, Prague. METHODS: Analysis of
      incidences of CM and chromosomal aberrations in live- and stillbirths and their
      number in prenatally diagnosed cases in the Czech Republic in 2001. Data On CM
      incidences were obtained form those registered in statistical reports (CM in a
      fetus or a child) collected through the Institute of Health Information and
      Statistics of the Czech Republic (UZIS). Data available by the end of October
      2002 were analysed. Supplementary data on prenatal diagnostics cases were
      obtained from particular departments of medical genetics in the Czech Republic.
      RESULTS: There were 90,715 livebirths in 2001 compared to 90,910 livebirths in
      2000. The total number of children with CM in 2001 was 3,572 additional 457 cases
      were diagnosed prenatally and the pregnancies were terminated, whereas in 2000,
      3,751 children with CM were born and 425 cases were diagnosed prenatally (and
      pregnancies were terminated). CONCLUSION: Data analysis from the CM registration
      in the Czech Republic has continued also in 2001 due to a good collaboration with
      both UZIS and particular departments of medical genetics. The total number of
      registered CM cases in livebirths is increasing in the last years, despite of
      prenatal diagnostics techniques level, which is comparable to the level in the
      most advanced countries.

PMID- 14692352
TI  - [Does the decreasing rate of neonatal mortality increase severe neonatal
      neurosensory morbidity?].
AB  - OBJECTIVE: To investigate relation between the mortality and the incidence of
      serious neonatal neurosensoric morbidity in very low birth weight newborns
      (VLBWN, birth weigh < or = 1499 g) during the three periods as defined by
      different quality of the parinatal and neonatal care. DESIGN: Retrospective
      analysis. SETTING: Perinatal center of the General Faculty Hospital. 1st Medical
      Faculty Charles University, Prague. SUBJECT AND METHODS: All live-born VLBWN in
      1987-2001 were divided according to their birth-date to three five-year periods
      characterized by different quality of the perinatal and neonatal care. Ist period
      1987-1991: the presurfactant area with no standard use of antenatal steroids and
      without defined border of the fetus viability; IInd period 1992-1996: the
      transient aera; IIIrd period 1997-2001: the surfactant aera with standard use of
      the antenatal steroids, and defined border of the fetus viability. VLBWN were
      divided according to birth weight to three subgroups (p. h. < 750 g, p. h. = 750
      999 g, p. h. = 1000-1499 g). Mortality was defined by a death in our department
      until the discharge. VLBW newborns classified as newborns with serious neonatal
      neurosensoric morbidity (NNsM) had to have one of the following diagnoses at
      least: severe intraventricular haemorrhage (IVH gr. 3-4), posthemorhagic
      hydrocephaly (PHH), cystic periventricular leukomalacia (cPVL), meningitis,
      ventriculitis, encephalitis (M/E), retinopathy of prematurity > or = stage III
      (ROP > or = III st.). The chi 2 test was used for statistic evaluation. RESULTS:
      There were 873 VLBWN born and 208 of them died in the whole period (1987-2001).
      Mortality decreased in 5 year periods gradually: 1st period 111/226 (49%); IInd
      period 55/217 (25%); IIIrd period 42/430 (10%). The decrease of mortality was
      significant in all weight categories (p < 0.001). The incidence of NNsM was
      evaluated in 612 newborns and was similar in all periods regarding weight
      subcategories < 1000 g, but decreased significantly in the weight category 1000
      1499 g (14/215 (6%) vs 13/73 (18%), p < 0.01). CONCLUSION: Improvement in
      survival of extremely low birth-weight infants did not increase the incidence of
      serious neurosensoric morbidity and evenmore NNsM was reduced in haevier very
      premature newborns during the nineties.

PMID- 14692353
TI  - [The May-Hegglin anomaly in pregnancy. 2 case reports].
AB  - TYPE OF STUDY: Case report. SETTING: Obstetrics and Gynecology Department, 2nd
      Medical Faculty Charles University and Faculty Hospital Motol, Department of
      Hematology and blood transfusion, Obstetrics and Gynecology Department, 1st
      Medical Faculty Charles University and General Faculty Hospital, Prague. METHODS:
      The authors present two cases of pregnant women with May-Hegglin anomaly. This
      rare hereditary trombocytopenia is characterized with the presence of
      megathrombocytes and typical basophilie inclusions (Dahli's inclusions) in
      granulocyte cytoplasma in blood count. Clinically, there are possible
      haemmorrhagic manifestations in this anomaly [13]. The course of pregnancy was
      uncomplicated in both cases. The values of thrombocytes fluctuated between 22-34
      x 10(9)/l and 17-27 x 10(9)/l respectively. The response on the corticosteroid
      administration was minimal. The pregnancy was terminated with caesarean section
      in general anesthesia in both cases. The indication in the first case was, after
      the neonatologist consultation with hematologist on duty, the anomaly itself. In
      the second case it was primarily decided to conduct the labor vaginally. It was
      necessary to start the induction of labor for the development preeclamptic signs.
      This prostaglandin induction was unsuccessful and therefor was the labor also
      terminated with s.c. Both delivered neonates were in good condition without
      clinical or lab signs of the disease. The neonate in the second case was of
      borderline trophicity. The s.c. were secured with transfusions of thrombocytes
      and carried out without any complications in both cases. The blood losses were
      400 and 700 ml without necessity of erythrocyte transfusions. The postoperative
      course was also uncomplicated in both cases. Both women with their children were
      released from hospital on the 6th postoperative day. CONCLUSION: There are about
      20 published papers of authors describing pregnancy with this rare anomaly. The
      efforts of haemmorrhage are very rare, the course of pregnancy is usually not
      disturbed [7, 8, 9, 11]. Some authors alert on possible higher risk intrauterine
      growth restriction [4]. The risk of fetal hemorrhage is from all available, data
      also small and there is no need of prenatal invasive investigation
      (cordocentesis) [11]. The mode of delivery depends only on the obstetrics and
      indications, vaginal labor is not associated with higher risk for the fetus [2,
      3, 5, 6, 10]. The treatment with corticosteroids or immunoglobulins in cases when
      the clinical symptomatology appear is only little effective, administration of
      thrombocytes transfusions are useful [8, 9]. When the anesthesia is necessary,
      general anesthesia is preferred because of higher risk of local haemmorrhage
      complications in cases of epidural or spinal analgesia [10, 14].

PMID- 14692354
TI  - [Successful postponement of delivery in twin pregnancy].
AB  - OBJECTIVE: Description of twin pregnancy after IVF preterm rupture of membranes
      of fetus A in 22nd gestational week. Abortion of fetus A and successful delayed
      delivery of twin B. DESIGN: Case report. SETTING: Obstetrics and Gynecology
      Department, 2nd Medical Faculty Charles University and Faculty Hospital Motol,
      Obstetrics and Gynecology Department, 1st Medical Faculty Charles University and
      General Faculty Hospital, Prague. METHODS: Patient A. S. 34 years old, admitted
      to the hospital in 23rd gestational week with preterm rupture of membranes of
      fetus A, after appearing spontaneous uterine contractions terminated the abortion
      of fetus A. The uterine contractions stopped with toxolytics and after one week
      of expectation interval the cerclage suture of cervix was performed. The
      following course of pregnancy was protected with antibiotics and 48 hours
      toxolysis with beta mimetics. The pregnancy continued without any serious
      complications till 37th gestational week, when infectious markers elevated.
      Cerclage suture was taken away and after 12 hours interval the labor started. The
      labor was terminated with s.c. because of imminent fetal hypoxia. CONCLUSION:
      After the abortion of twin A we succeeded to delay delivery interval for 4
      months. The borderline mature neonate was born in good clinical condition and
      survived without any serious complications.

PMID- 14692355
TI  - [Effect of acute urological complications on the course of pregnancy].
AB  - OBJECTIVE: To evaluate influence of acute urological cases (AUC) on course and
      results of pregnancies. DESIGN: Retrospective clinical study. SETTING: 1st
      Department of Gynaecology and Obstetrics, Department Urology Faculty Hospital,
      Kosice, Slovakia. METHODS: 40 pregnant women with AUC aged 15-34 years (average
      24) which delivered at our Department. RESULTS: The most often occurrence of AUC
      was in the 2nd and 3rd trimester of pregnancies. 62.5% women were primiparas. The
      most frequent urological complication was acute pyelonephritis (APNP)-23 (57%)
      patients, more often on the right side 4.75: 1. 27 patients (67.5%) had renal
      colic, more often presents on the right side (6:1). 83% women had infection of
      urinary tract (IUT). 34 (85%) women were treated by antibiotics or
      urodesinficiens. 70% pregnancies were closed as intact pregnancies without
      intrauterine risk of the fetus. Signs of premature labour had 8 patients (20%),
      hypotrophy of the fetus was evaluated in two patients (5%) and 2 pregnancies were
      terminated by caesarean section due to intrauterine asphyxia of the fetus. We
      identified nearly double increase of premature labours in the group of women with
      AUC in opposition to average in 1998 at Kosice district. Risk of newborn early
      asphyxia syndrome at the 1. minute is important (12.5%). CONCLUSION: Almost 1/3
      pregnancies with AUC have obstetrical complication. Most common incidence of AUC
      is at the first gravidity, at the right side. AUC require complete obstetrical
      and urological examination with adequate therapy. We can reduce incidence by
      careful prenatal care and therapy.

PMID- 14692356
TI  - [A transdermal form of combined hormonal contraceptives (EVRA)].
AB  - OBJECTIVE: To present a review of a novel transdermal contraceptive patch
      containing norelgestromin (150 micrograms/d) and ethinylestradiol (20
      micrograms/d). DESIGN: Review article. SETTING: Department of Gynecology and
      Obstetric, 1st Medical Faculty and General Faculty Hospital, Prague. RESULTS: The
      contraceptive patch exhibits favourable pharmakokinetic profile, maintaining
      efficacious serum hormone concentrations under varying conditions and without
      peaks and through characteristic of oral dosing. Efficacy, cycle control,
      tolerability and side effect profile were comparable to an established oral
      contraceptive. Compliance with the weekly administered contraceptive patch was
      significantly better than with an oral contraceptive. The reliability of adhesion
      of the patch is very high and consistent even under varying conditions (heat,
      humidity, exercise).

PMID- 14692357
TI  - [What the Bethesda II/2001 System can give to gynecologists and what they
      require].

PMID- 14692358
TI  - [Rape--diagnosis, care and specimen collection for forensic purposes].

PMID- 14692359
TI  - [Treatment of women who have been raped].

PMID- 14692360
TI  - [Current legal aspects of reproductive medicine].

PMID- 14692361
TI  - [Psychological aspects of perinatal medicine 1980 to 2000: II. Childbirth].

PMID- 14692362
TI  - Outgoing president's address, 2003 conference: reflections: proud, but not
      content.

PMID- 14692363
TI  - Finding and evaluating potential research instruments.
AB  - In this column, I have outlined some of the basic strategies for finding
      appropriate research instruments and for evaluating them so that you can
      determine the best one to use for your own research. These strategies, as basic
      as they are, will help to guide you as you make decisions. Of course, there are
      complex issues surrounding the development and refinement of research instruments
      and you would do well to review reliability, validity, and sensitivity in
      research texts before choosing an instrument.

PMID- 14692364
TI  - Managing bowel obstruction in ovarian cancer using a percutaneous endoscopic
      gastrostomy (PEG) tube.
AB  - An estimated 2,500 women were diagnosed with and 1,500 died from ovarian cancer
      in Canada in 2002. Up to 42% of patients in the palliative phase develop a
      malignant bowel obstruction. Options for management include medical therapy,
      surgery, and/or a percutaneous endoscopic gastrostomy (PEG) tube. The objective
      of this quality improvement study was to: 1) examine if successful palliation was
      achieved using a PEG tube, and 2) identify opportunities to improve the quality
      of nursing care provided. A retrospective review of 24 patient records revealed
      that 75% did not have nausea/vomiting by time of discharge; 92% resumed a clear
      fluid diet; 83% were discharged from the acute care setting; and 70% did not
      require re-admission. A PEG tube may effectively palliate women with non-operable
      bowel obstruction in advanced/recurrent cancer of the ovary. Opportunities for
      improving care are presented.

PMID- 14692365
TI  - The needs of family members of patients receiving radioactive iodine.
AB  - The current literature on radionuclide therapy is heavily based on health care
      professionals' perspectives and provides little insight regarding what patients
      or family members identify as their needs or concerns. Family members (N = 130)
      of patients undergoing treatment with radioactive iodine were selected from eight
      programs across Canada to participate in a survey to identify the needs they had
      when a close relative was undergoing treatment with radioactive iodine. The
      results of the survey indicated family members experienced worries and concerns
      about the patient being at home after treatment, and there was variation in their
      knowledge about what precautions were needed. Family members provided evidence
      that many experienced psychosocial distress, but very few received adequate
      assistance for their difficulties.

PMID- 14692366
TI  - [Children with cancer and their symptom experience: spiritual support of the
      children and their families].

PMID- 14692367
TI  - Febrile neutropenia: are you up to date?

PMID- 14692368
TI  - Position statements, technical reviews, and white papers: understanding the
      differences.

PMID- 14692369
TI  - Early combination therapy with a thiazolidinedione for the treatment of type 2
      diabetes.

PMID- 14692370
TI  - A multidisciplinary approach in a community pharmacy can improve outcomes for
      diabetes patients.

PMID- 14692371
TI  - A tribute to Donnell D. Etzwiler, MD: Innovator, Leader, and Educator.

PMID- 14692372
TI  - The history of diabetes nursing, 1914-1936.

PMID- 14692373
TI  - The family context of an intervention to prevent type 2 diabetes in high-risk
      teens.
AB  - PURPOSE: This research describes the family context of eating and mealtime
      patterns in young adolescents at high risk for type 2 diabetes and the
      implications for preventing this disease. METHODS: Ten families, each consisting
      of a child and one parent, participated in individual, semistructured interviews
      that focused on family eating patterns. Topics included meal schedules, food
      preparation, family eating patterns, school eating patterns, and perception of
      the child's weight. Interviews were audiotaped, transcribed verbatim, and
      analyzed using focused summaries and thematic analysis methods. RESULTS: Four
      main themes were identified: child and family eating patterns, perspectives on
      obesity, perspectives on weight control, and health concerns. Family eating
      patterns were often inconsistent, and few healthy eating models were available at
      home or school. Obesity was not always seen as a negative factor, particularly by
      the youth. Weight-control efforts were sporadic, typically unsuccessful, and
      consisted primarily of intermittent increases in physical activity. Parents did
      not actively participate in their child's weight-control efforts. CONCLUSIONS:
      Effective interventions for obesity and prevention of type 2 diabetes in youth
      should include parents in both cognitive and behavioral strategies.

PMID- 14692374
TI  - Use of cognitive interviewing to adapt measurement instruments for low-literate
      Hispanics.
AB  - PURPOSE: Cognitive interviewing techniques were used to adapt existing measures
      for use with a population of low-literate Spanish-speaking people with diabetes.
      METHODS: Five individuals of Caribbean origin with diabetes participated in
      cognitive interviews for 4 instruments (measuring diabetes knowledge, quality of
      life, self-management, and depression) adapted for oral administration to low
      literate individuals. Audiotaped interviews and handwritten notes were subjected
      to content analysis to identify problems across the 4 instruments as well as
      specific to a given instrument. RESULTS: The following key problems were
      identified: general instructions were not helpful, items that were not specific
      enough generated a variety of interpretations, some wording was confusing,
      abstract concepts were difficult to understand, some terminology was unfamiliar,
      and interpretation of certain words was incorrect. CONCLUSIONS: The data
      illustrate the usefulness of cognitive interviewing as a first step in the
      process of adapting measurement instruments.

PMID- 14692375
TI  - A qualitative study of problem solving and diabetes control in type 2 diabetes
      self-management.
AB  - PURPOSE: The purpose of this study was to explore and compare diabetes-related
      problem solving in urban African Americans in good and poor diabetes control.
      METHODS: Two focus groups were conducted, one with participants in good diabetes
      control and one with participants in poor control. Based on a theoretical model,
      focus group interview questions were designed to elicit responses about 3 aspects
      of diabetes-related problem solving: (1) problem-solving orientation, (2) problem
      solving process, and (3) transfer of past experience. Transcripts were analyzed
      using a qualitative data analysis software program, and expert panel members
      independently reviewed responses and coding. RESULTS: The primary types of
      problems with diabetes self-management were similar in the good control and poor
      control groups. Predominant problem-solving themes in the good control group
      reflected a positive orientation toward diabetes self-management and problem
      solving, a rational problem-solving process, and a positive transfer of past
      experience. In contrast, predominant themes in the poor control group revealed a
      negative orientation, careless and avoidant problem-solving processes, and
      negative transfer of past learning to new situations. CONCLUSIONS: The problem
      solving model may help identify ineffective problem-solving patterns in persons
      with poor diabetes control. Empirical studies testing the model are warranted.

PMID- 14692377
TI  - [Susceptibilities of bacteria isolated from patients with lower respiratory
      infectious diseases to antibiotics (2001)].
AB  - From October 2001 to September 2002, we collected the specimen from 370 patients
      with lower respiratory tract infections in 16 institutions in Japan, and
      investigated the susceptibilities of the isolated bacteria to various
      antibacterial agents and antibiotics and patients' characteristics. Of 458
      strains that were isolated from specimen (mainly from sputum) and assumed to be
      bacteria causing in inflammation, 456 strains were investigated. The breakdown of
      the isolated bacteria were: Staphylococcus aureus 69, Streptococcus pneumoniae
      72, Haemophilus influenzae 85, Pseudomonas aeruginosa (non-mucoid) 44, P.
      aeruginosa (mucoid) 13, Klebsiella pneumoniae 32, Moraxella subgenus Branhamella
      catarrhalis 32, and others. Of 69 S. aureus strains, those with 4 micrograms/mL
      or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied
      43.5%. Vancomycin and arbekacin showed the most potent activities against MRSA as
      observed in 2000. The frequency of S. pneumoniae exhibiting low sensitivity to
      penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S.
      pneumoniae: PRSP) was 59.7% and both rates of PISP and PRSP were the highest
      after 1992. Carbapenems had strong activities against S. pneumoniae. Especially,
      panipenem and imipenem inhibited the growth of all 72 strains at 0.125 and 0.5
      microgram/mL, respectively. Generally, all drugs had strong activities against H.
      influenzae with MIC90s of 16 micrograms/mL or less. The drug that had the
      strongest activity against H. influenzae was levofloxacin, which inhibited the
      growth of 80 of the 85 strains at 0.063 microgram/mL. Against P. aeruginosa
      mucoid strain, meropenem had a strong activity with MIC90 of 0.5 microgram/mL
      while, against non-mucoid strain, tobramycin had a strong activity with MIC90 of
      2 micrograms/mL. K. pneumoniae showed good susceptibilities to all drugs except
      ampicillin and minocycline, and the MIC90s were 4 micrograms/mL or less.
      Particularly, cefmenoxime, cefpirome, and imipenem had the strongest activity
      (MIC90: 0.125 microgram/mL), and cefozopran had a strong activity, inhibiting the
      growth of all strains at 0.25 microgram/mL. Also, all drugs generally had strong
      activities against M. (B.) catarrhalis. MIC90s of all drugs were 4 micrograms/mL
      or less. The drug that had the strongest activity was minocycline and
      levofloxacin inhibiting all 32 strains at 0.063 microgram/mL. Most of the
      patients with respiratory infection were aged 70 years or older, accounting for
      approximately a half of the total (40.5%). As for the incidence by the diseases,
      bacterial pneumonia and chronic bronchitis were the highest, being noted in 39.2%
      and 37.3% of all the patients, respectively. The bacteria frequently isolated
      from the patients with bacterial pneumonia were S. aureus (19.3%) and S.
      pneumoniae (19.9%). In contrast, H. influenzae (22.0%) were frequently isolated
      from the patients with chronic bronchitis. Before the drug administration, the
      bacteria frequently isolated from the patients were S. pneumoniae (20.8%) and H.
      influenzae (21.5%). S. pneumoniae and H. influenzae decreased after the
      initiation of drug administration while S. aureus increased. The isolation
      frequency of P. aeruginosa was higher after than before the initiation of drug
      administration. The bacteria were frequently isolated from the patients who had
      already treated with cephems were S. aureus and P. aeruginosa. From the patients
      who had already treated with macrolides, S. pneumoniae was the most frequently
      isolated while S. aureus was the most frequently isolated from the patients pre
      treated with quinolones.

PMID- 14692376
TI  - [Activities of antimicrobial agents against 8,474 clinical isolates obtained from
      37 medical institutions during 2000 in Japan].
AB  - A survey was conducted to determine the antimicrobial activity of
      fluoroquinolones and other antimicrobial agents against 8,474 clinical isolates
      obtained from 37 Japanese medical institutions in 2000. A total of 25
      antimicrobial agents were used, comprising 4 fluoroquinolones, 13 beta-lactams,
      minocycline, chloramphenicol, clarithromycin, azithromycin, gentamicin, amikacin,
      sulfamethoxazole-trimethoprim, and vancomycin. A high resistance rate of over 85%
      against fluoroquinolones was exhibited by methicillin-resistant Staphylococcus
      aureus (MRSA) and Enterococcus faecium. Isolates showing resistance to
      fluoroquinolones among methicillin-resistant coagulase-negative Staphylococci,
      Enterococcus faecalis, and Pseudomonas aeruginosa from UTI accounted for 30-60%.
      However, many of the common pathogens were still susceptible to fluoroquinolones,
      such as Streptococcus pneumoniae (including penicillin-resistant isolates),
      Streptococcus pyogenes, methicillin-susceptible S. aureus (MSSA), methicillin
      susceptible coagulase-negative Staphylococci, Moraxella catarrhalis, the
      Enterobacteriaceae family, and Haemophilus influenzae (including ampicillin
      resistant isolates). About 85% of P. aeruginosa isolated from RTI were
      susceptible to fluoroquinolones. In conclusion, this survey of sensitivity to
      antimicrobial agents clearly indicated trend for increasing resistance to
      fluoroquinolones among MRSA, Enterococci, and P. aeruginosa isolated from UTI,
      although fluoroquinolones are still effective against other organisms and P.
      aeruginosa from RTI as has been demonstrated in previous studies.

PMID- 14692378
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from patients with urinary tract infections (2001). I.
      Susceptibility distribution].
AB  - The bacterial strains isolated from patients diagnosed as having urinary tract
      infections (UTIs) in 10 institutions in Japan were supplied between the period of
      September and December 2001. Then, the susceptibilities of them to a variety of
      antimicrobial agents were investigated. The number of them were 496 strains. The
      breakdown of these strains was Gram-positive bacteria as 29.6% and Gram-negative
      bacteria as 70.4%. Susceptibilities of these bacteria to antimicrobial agents
      were as follows; against Staphylococcus aureus, vancomycin (VCM) showed a strong
      activity, and this drug also had a strong activity against MRSA in preventing
      growth of all strains at 1 microgram/mL. In addition, arbekacin (ABK) showed
      strong activity with the MIC90 of 2 micrograms/mL against MRSA and prevented
      growth of all strains at 4 micrograms/mL. ABK also showed a strong activity
      against Staphylococcus epidermidis in preventing growth of all strains at 0.5
      microgram/mL. Ampicillin (ABPC) and cefozopran (CZOP) showed a relatively strong
      activity against S. epidermidis (MIC90: 8 micrograms/mL). ABPC, imipenem (IPM),
      and VCM showed strong activities against Enterococcus faecalis. No increase of
      low-susceptible strains in E. faecalis was observed against these antimicrobial
      agents. Against Escherichia coli, carbapenems showed the highest activities:
      meropenem (MEPM) prevented growth of all strains at 0.25 microgram/mL; IPM
      prevented growth of all strains at 0.5 microgram/mL. CZOP and cefotiam (CTM) also
      showed strong activities against E. coli: MIC90 of CZOP was within 0.125
      microgram/mL; MIC90 of CTM was within 0.5 microgram/mL. Quinolone-resistant E.
      coli was detected at frequency of 9.3%, which was lower than that in the last
      year, and was higher level than those in up to 1999. MEPM showed the strongest
      activity against Citrobacter freundii in preventing growth of all strains at
      0.125 microgram/mL. Almost all drugs showed strong activities against Klebsiella
      pneumoniae and Proteus mirabilis, and MEPM prevented growth of all strains within
      0.125 microgram/mL. Against Serratia marcescens, the MIC90 of gentamicin (GM) was
      the lowest value being 2 micrograms/mL, and those of IPM and carumonam were 8 and
      16 micrograms/mL, respectively. Against Pseudomonas aeruginosa, almost all drugs
      were not so active. The MIC90 of GM was 8 micrograms/mL, those of IPM and
      amikacin were 16 micrograms/mL, and those of all other drugs were over than 32
      micrograms/mL.

PMID- 14692380
TI  - [Post-marketing surveillance of antibacterial activities of cefozopran against
      various clinical isolates--I. Gram-positive bacteria].
AB  - As a post-marketing surveillance, the in vitro antibacterial activities of
      cefozopran (CZOP), an agent of cephems, against various clinical isolates were
      yearly evaluated and compared with those of other cephems, oxacephems,
      penicillins, and carbapenems. Changes in the bacterial susceptibility for CZOP
      were also evaluated with the resistance ratio calculated with breakpoint MIC.
      Sixteen species (2,363 strains) of Gram-positive bacteria were isolated from the
      clinical materials annually collected from 1996 to 2001, and consisted of
      methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant
      Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus epidermidis
      (MSSE), methicillin-resistant Staphylococcus epidermidis (MRSE), Staphylococcus
      haemolyticus, Staphylococcus saprophyticus, Enterococcus faecalis, Enterococcus
      faecium, Enterococcus avium, Streptococcus pyogenes, Streptococcus agalactiae,
      penicillin-susceptible Streptococcus pneumoniae (PSSP), penicillin-intermediate
      resistant S. pneumoniae (PISP), penicillin-resistant S. pneumoniae (PRSP),
      Streptococcus milleri group and Peptostreptococcus spp. The antibacterial
      activity of CZOP either against MSSA or MSSE was preferable (MIC90: 2 or 0.5
      micrograms/mL) and comparable to those of other cephems. CZOP was also effective
      on MRSE (MIC90: 16 micrograms/mL) but not on MRSA. CZOP and other cephems had low
      antibacterial activity against S. haemolyticus (MIC90: 64 micrograms/mL). The
      antibacterial activity of CZOP against S. saprophyticus was comparable to or
      higher than those of other cephems, but the MIC90 of CZOP in 2001 was higher than
      those in 1996-2000 (32 vs 1-2 micrograms/mL). The antibacterial activity of CZOP
      against E. faecalis was comparable to that of cefpirome (CPR; MIC90: 16
      micrograms/mL) and higher than those of other cephems. No antibacterial activity
      of CZOP against E. faecium and E. avium was observed, like other drugs. The
      antibacterial activity of CZOP against S. pyogenes was as potent as those of
      cefotiam and CPR (MIC90: < or = 0.063 microgram/mL), and, against S. agalactiae,
      was also preferable (MIC90: 0.125 microgram/mL). CZOP indicated preferable
      antibacterial activity either against PSSP, PISP, or PRSP (MIC90: 0.25, 1, or 2
      micrograms/mL). The antibacterial activity of CZOP against S. milleri group was
      also preferable, but the MIC90 of CZOP in 2001 was higher than those in 1996-2000
      (4 vs 0.5 micrograms/mL). The antibacterial activity of CZOP against
      Peptostreptococcus spp. was preferable but weaker than those of cefazolin and
      cefmetazole. The resistance ratio estimated from breakpoint MIC of CZOP was 95.9%
      in MRSA, 93.5% in PRSP, 63.3% in PISP, 35.8% in S. haemolyticus, 27.9% in E.
      faecalis, and 13.3% MRSE. Those resistance ratios were comparable to those for
      cefepime (CFPM), but E. faecalis showed 91.2% for CFPM. The difference in the
      resistance ratio of E. faecalis demonstrated that CZOP successfully maintained
      its antibacterial activity against these species. In correlation of drug
      susceptibility, 40.3% of PRSP was not inhibited at breakpoint MIC either CZOP or
      CFPM while 69.2% at breakpoint MIC either CZOP or ceftazidime. In conclusion, the
      antibacterial activities of CZOP against the Gram-positive bacteria obtained from
      the 6-year duration study were consistent with the results from the studies
      performed until the new drug application approval. A decline in the sensitivities
      of S. saprophyticus, S. milleri group, PISP, and PRSP to CZOP, however, was
      suggested.

PMID- 14692379
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from patients with urinary tract infections (2001). II.
      Background of patients].
AB  - Five-hundred thirty one bacterial strains isolated from 412 patients diagnosed as
      having urinary tract infections (UTIs) in 10 institutions in Japan were supplied
      between September and December 2001. Then, the clinical background of patients
      were investigated such as sex, age, and type of infections, infections and kind
      of bacteria, frequency of bacteria isolation by age and infections, bacteria and
      infections by timing of antibiotics administration, and bacteria and infections
      by surgical procedures. With regard to the relationship between age and sex of
      patients and type of infections, the number of cases aged lower than 50 years was
      few and complicated UTIs without indwelling catheter was the most frequent in
      male patients. In females, the number of patients aged lower than 20 years was
      few. Most of female patients aged lower than 80 years had uncomplicated UTIs. As
      for the relationship between type of infections and kind of bacteria, Escherichia
      coli decreased as the infections were more complicated, and Pseudomonas
      aeruginosa and Enterococcus faecalis increased as the infections were more
      complicated. In relation of these results to age of patients, isolation frequency
      of E. coli gradually decreased with aging in patients aged 20 years and older
      with uncomplicated UTIs. The isolation frequencies of E. faecalis decreased with
      aging in the patients with complicated UTIs without indwelling catheter while P.
      aeruginosa decreased with aging in the patients with complicated UTIs with
      indwelling catheter. E. coli was isolated a few after administration of
      antibiotics, and P. aeruginosa and E. faecalis were frequently isolated after
      administration in the patients with all types of infections. As for type of
      causative organisms in UTIs and with or without surgical operation, E. coli was
      frequently isolated in the patients without surgery in the patients with
      uncomplicated UTIs and complicated UTIs without indwelling catheter, while P.
      aeruginosa was frequently isolated in the patients who underwent surgery in the
      patients with uncomplicated UTIs and complicated UTIs with indwelling catheter.
      In uncomplicated UTIs, isolation frequencies of Klebsiella spp., P. aeruginosa,
      and E. faecalis were significant in the patients with surgery. In complicated
      UTIs without indwelling catheter, Klebsiella spp. was frequently isolated in the
      patients with surgery. In complicated UTIs with indwelling catheter, S. aureus
      and Staphylococcus spp. were frequently isolated in the patients without surgery.

PMID- 14692381
TI  - [Post-marketing surveillance of antibacterial activities of cefozopran against
      various clinical isolates--II. Gram-negative bacteria].
AB  - As a post-marketing surveillance, the in vitro antibacterial activities of
      cefozopran (CZOP), an agent of cephems, against various clinical isolates were
      yearly evaluated and compared with those of other cephems, oxacephems,
      carbapenems, monobactams, and penicillins. Changes in CZOP susceptibility among
      bacteria were also evaluated with the bacterial resistance ratio calculated from
      the breakpoint MIC. Twenty-five species (4,154 strains) of Gram-negative bacteria
      were isolated from the clinical materials annually collected from 1996 to 2001,
      and consisted of Moraxella (Branhamella) catarrhalis, Haemophilus influenzae,
      Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter
      cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens,
      Citrobacter freundii, Citrobacter koseri, Proteus mirabilis, Proteus vulgaris,
      Morganella morganii, Providencia spp., Pseudomonas aeruginosa, Pseudomonas
      fluorescens, Pseudomonas putida, Acinetobacter baumannii, Acinetobacter Iwoffii,
      Burkholderia cepacia, Stenotrophomonas maltophilia, Bacteroides fragilis group,
      and Prevotella/Porphyromonas. CZOP preserved its antibacterial activity against
      M. (B.) catarrhalis (MIC90: 4 micrograms/mL) and showed comparable activity to
      carbapenems against H. influenzae (MIC90: 1 microgram/mL). The antibacterial
      activity of CZOP against E. coli was preferable (MIC90: 0.125 microgram/mL) and
      comparable to those of cefpirome (CPR), cefepime (CFPM), and imipenem (IPM). The
      MIC90 of CZOP against K. pneumoniae and K. oxytoca was 1 and 0.25 microgram/mL,
      respectively. The MIC90 of CZOP against E. cloacae increased during 6 years (32
      to 128 micrograms/mL). The antibacterial activity of CZOP against E. aerogenes
      was preferable (MIC90: 1 microgram/mL). The antibacterial activities of CZOP
      against S. marcescens and S. liquefaciens were relatively potent (MIC90: 0.5 and
      0.25 microgram/mL) and comparable to those of CPR, CFPM, and carumonam. CZOP
      preserved comparable antibacterial activity to CPR against C. freundii and C.
      koseri (MIC90: 8 and 0.125 micrograms/mL). The MIC90 of CZOP against P.
      mirabilis, P. vulgaris, and M. morganii was 0.25, 16, and 2 micrograms/mL,
      respectively. The antibacterial activity of CZOP against Providencia spp. was
      moderate (MIC90: 64 micrograms/mL). The antibacterial activity of CZOP against P.
      aeruginosa was the most potent (MIC90: 16 micrograms/mL) among the test agents
      and comparable to those CFPM, IPM, and MEPM. CZOP had low activity against P.
      fluorescens and P. putida (MIC90: 128 micrograms/mL). The antibacterial activity
      of CZOP against A. baumannii was comparable to those of ceftazidime (CAZ), CPR
      and CFPM (MIC90: 32 micrograms/mL) and against A. lwoffii was moderate (MIC90: 64
      micrograms/mL). Most of the test agents including CZOP had low antibacterial
      activity against B. cepacia, S. maltophilia, and B. fragilis group. The MIC90 of
      CZOP against Prevotella/Porphyromonas was 64 micrograms/mL. Bacterial cross
      resistance ratio between CZOP and other agents was low in most of the species,
      ranging from 0.0 to 15.1%. In non-glucose fermentative bacteria, however, the
      bacterial cross-resistance ratio between CZOP and CFPM, CAZ, CPR, or IPM was
      high, being 36.8%, 28.0%, 38.7%, or 31.1%, respectively. In conclusion, the 6
      year duration study suggested that the antibacterial activity of CZOP against E.
      cloacae possible decreased, but against other Gram-negative bacteria was
      consistent with the study results obtained until the new drug application
      approval.

PMID- 14692382
TI  - Educating staff on tracer methodology is a must: survey results depend on it.

PMID- 14692383
TI  - Comparative performance data now ready for use.

PMID- 14692384
TI  - Boost patient satisfaction while enhancing safety.

PMID- 14692385
TI  - New program helps breast cancer patients.

PMID- 14692386
TI  - Quality control is major theme during survey.

PMID- 14692387
TI  - Gathering and reporting CPR performance data.

PMID- 14692388
TI  - Echocontrast agent-enhanced color flow imaging of the breast.

PMID- 14692389
TI  - Patient's perception of pain on admission and discharge from the emergency
      department.
AB  - Patients presenting to the emergency department have a common complaint of pain.
      Whether admitted to the hospital or discharged to home, patients are leaving the
      emergency department in a higher level of pain than would be considered tolerable
      or comfortable. Pain can be a major impediment to an adequate quality of life.
      Unrelieved or chronic pain causes anxiety, depression, sleep disturbances,
      decreased self-esteem and self-worth, inactivity, altered family dynamics,
      financial stress and an increase in the number of health-care visits. The purpose
      of this study was to evaluate patients' perception and report of pain in the ED
      from the time of arrival to the time of discharge. The sample consisted of 63
      females and 62 males from an ED of an urban hospital in Trenton, New Jersey. The
      mean age for the males was 40 years, and the mean age for the females was 41
      years. The pain level of the participants was measured by the use of a visual
      analogue scale at the time of arrival and at the time of discharge from the ED. A
      paired t-test for related samples revealed that the VAS scores decreased from
      5.90 to 3.38 (p = .000).

PMID- 14692391
TI  - Healthcare professionals warned over patient confidentiality.

PMID- 14692390
TI  - Alarm caused by sedation of older people report.

PMID- 14692392
TI  - Poor intravenous therapy administration by nurses puts patients at risk.

PMID- 14692393
TI  - Older people must get a better deal in hospital.

PMID- 14692394
TI  - Concern about attitude over MMR vaccine.

PMID- 14692395
TI  - [What is the cause of pulse-synchronized ringing in the ears in the elderly and
      is it possible to treat it?].

PMID- 14692396
TI  - Apoptosis and oxidative status in peripheral blood mononuclear cells of diabetic
      patients.
AB  - We have compared the concentrations of intracellular glutathione (GSH),
      glutathione-dependent antioxidative enzymes, the cell death rate and
      immunophenotype profile of peripheral blood mononuclear cells (PBMC) from healthy
      donors and from patients with insulin-dependent type II (NIDDM) diabetes
      mellitus. The IDDM and NIDDM patients had above-normal absolute lymphocyte
      counts, whereas the percentages of CD3, CD4 adn CD8 T lymphocytes were
      significantly reduced. In contrast, the absolute number and percentage of B
      lymphocytes was higher in diabetic patients than in healthy donors. The low
      intracellular reduced glutathione(GSH) and the unbalanced profile of key enzymes
      involved in GSH metabolism, gamma-glutamyltransferase (gamma-GT) and glutathione
      S-transferase (GST), account for the increased oxidative status of PBMC from
      diabetic patients. The plasma membranes of PBMC for diabetic patients were less
      permeable to propidium iodide than those of PBMC from healthy donors, indicating
      that the apoptotic cell death rate was lower in the cells from diabetic patients.
      These differences are potentially useful markers of pathogenic metabolic changes
      which occur during clinical diabetes and if they are confirmed could be use dot
      identify the onset of diabetes.

PMID- 14692397
TI  - Sustained suppression of Fas ligand expression in cisplatin-resistant human
      ovarian surface epithelial cancer cells.
AB  - Although cisplatin derivatives are first line chemotherapeutic agents for the
      treatment of ovarian epithelial cancer, chemoresistance is a major therapeutic
      problem. Although the cytotoxic effect of these agents are believed to be
      mediated through the induction of apoptosis, the role of the Fas/FasL system in
      chemoresistance in human ovarian epithelial cancer is not fully understood. In
      the present study, we have used cultures of established cell lines of cisplatin
      sensitive human ovarian epithelial tumours (OV2008 and A2780-s) and their
      resistant variants (C13* adn A2780-cp, respectively) to asses the role of
      Fas/FasL system in the chemo-responsiveness of ovarian cancer cell to cisplatin.
      Cisplatin was effective in inducing the expression of cell-associated Fas and
      FasL, soluble FasL and apoptosis in concentration and time-dependent fashion in
      both cisplatin-sensitive cell lines (OV2008 and A2780-s). In contrast, while
      cisplatin was effective in increasing cell-associated Fas protein content in
      C13*, it failed to up-regulate FasL (cell-associated and soluble forms) and
      induce apoptosis, irrespective of concentration and duration of cisplatin
      treatment. Concentrated spent media for OV208 cultures after cisplatin treatment
      were effective in inducing apoptosis in C13* cells which was partly inhibited by
      the antagonistic Fas monoclonal antibody (mAb) suggesting that the soluble FasL
      present in the spent media was biologically active. In the resistant A2780-cp
      cells, neither Fas nor FasL upregulation were evident in the presence of the
      chemotherapeutic agent and apoptosis remained low compared to its sensitive
      counterpart. Activation of the Fas signalling pathway, by addition to the
      cultures an agonistic Fas mAb, was equally effective in inducing apoptosis in the
      cisplatin-sensitive (OV2008) and -resistant variant C13*, although these
      responses were of lower magnitude compared to that observed with cisplatin in the
      chemosensitive cells. A significant interaction between cisplatin and agonistic
      Fas mAb was observed in the apoptotic response in OV2008 and C13* when cultured
      in the presence of both agents. Immunohistochemistry of human ovarian epithelial
      carcinomas reveals the presence of Fas in low abundance in proliferatively active
      cells but in high levels in quiescent ones. Although the expression pattern of
      FasL in the tumour was similar to tha tof Fas, the protein content was
      considerably lower. Taken together, these data suggest that the dysregulation of
      the Fas/FasL system may be an important determinant in cisplatin-resistance in
      ovarian epithelial cancer cells. Our results are also supportive of the notion
      that combined immuno- and chemo-therapy (i.e., agonistic Fas mAb plus cisplatin)
      may provide added benefits in the treatment of both chemo-sensitive and 
      resistant ovarian tumours.

PMID- 14692398
TI  - Modified approach for apoptosis detection reveals changes in apoptotic processes
      in the seminoma-associated tissue.
AB  - Apoptosis morphology (DNA condensation) and internucleosomal DNA cleavage (TdT
      assay) were measured simultaneously on double fluorescence labeled testis tumor
      sections, employing conventional immunofluorescence microscopy. Six different
      apoptosis indices (Al) were determined based either solely on morphological or
      biochemical criteria, or on a combination of both processes. Measurements were
      performed in metastasized and non-metastasized seminoma, and in histological
      regions located distantly and associated with the tumor. Preliminary results on
      19 histologies revealed that up to 66% of apoptotic cells were not detected,
      depending on the method used for apoptosis detection. Besides, no changes of
      solely morphologically defined Al was found in the different histological
      regions. By contrast, significant changes (p < 0.0004) in the different
      histological regions were detected when measuring Als, e.g., defined by DNA
      fragmentation occurring without DNA condensation in apoptotic cells. Those
      changes were not detected in metastasized seminoma. These data, for the first
      time allow a comparison of two widely used approaches for apoptosis detection.
      Furthermore, the results revealed differences in apoptotic processes in tissue
      associated with non-metastasized seminoma detectable by a modified evaluated TdT
      assay but not by morphological changes, although this TdT method fails to show
      the total amount fo apoptotic cells.

PMID- 14692399
TI  - Putative roles of retinoblastoma protein in apoptosis.
AB  - Cell numbers are regulated by a balance between processes of proliferation and
      apoptosis (programmed cell death). Proper regulation in a cell requires an
      accurate co-ordination between these two processes. Indeed, it has recently been
      found that dysregulation of cell cycle progression is essential for the
      initiation of apoptosis. Retinoblastoma protein (RB) is an important tumour
      suppressor and a cell cycle regulator. Most recent studies suggest that RB also
      plays a regulatory role in the process of apoptosis. During the onset of
      apoptosis, the hyperphosphorylated form of RB (p120/hyper) is converted to a
      hypophosphorylated form (p115/hypo), which is mediated by a specific protein
      serine/ threonine phosphatase activity. The p115/hypo/RB may play an active role
      in the regulation of apoptosis. Accompanied by the endonucleosomal fragmentation
      of DNA, the newly formed p115/hypo/RB is immediately cleaved by a protease that
      has properties of the interleukin-1beta-converting enzyme family. By contrast,
      the unphosphorylated form of RB (p110/unphos) remains uncleaved during apoptosis.
      Further studies suggest that p110/unphos/RB functions as an inhibitor of
      apoptosis. Therefore, a balance between RB phosphatases and kinases and
      consequent RB phosphorylation status may be important for the determination of
      cellular fate.

PMID- 14692400
TI  - Cellular resistance to vincristine suppresses NF-kappa B activation and apoptosis
      but enhances c-Jun-NH2-terminal protein kinase activation by tumor necrosis.
AB  - Tumor necrosis factor (TNF) is a pleiotropic cytokine that potentiates the
      cytotoxic effects of chemotherapeutic drugs. Although emergence of resistance to
      chemotherapeutic drugs is a major problem in cancer therapy, its mechanism is
      incompletely understood. Recently, activation of a nuclear transcription factor
      NF-kappa B has been reported to be a signal for anti-apoptosis. In this report,
      we investigated the effect of TNF on activation of NF-kappa B, c-Jun N-terminal
      kinase (JNK), and apoptosis in vincristine-resistant human histiocytic lymphoma
      U937-VR cells. Unlike the parent clone (U937-VS), no activation of caspase-3,
      known to be required for apoptosism was found in vincristine-resistant cells on
      exposure to vincristine. These cells were also more resistant than U-937-VS cells
      to doxorubicin, daunomycin, and taxol. TNF-induced NF-kappa B activation, I kappa
      B alpha degradation, and nuclear translocation of p65 were all found to be highly
      suppressed in the U-937-VR cells. NF-kappa B activation by LPS, H2O2, and okadaic
      acid was also suppressed. However, vincristine resistance enhanced TNF-induced
      JNK activation. When examined for apoptosis, vincristine resistance suppressed
      the cytotoxic effects and caspase-3 activation by TNF. The resistant phenotype in
      U937-VR cells was independent of the expression of the apoptosis-suppressor, Bcl
      2. Thus, overall these results indicate that vincristine resistance correlates
      with suppression of NF-kappa B activation, cytotoxicity, and caspase-3 activation
      but enhancement of JNK activation by TNF.

PMID- 14692401
TI  - Case 1: assessment. A new educational program for the parents of children with
      asthma.

PMID- 14692402
TI  - Case 2: assessment. A 17-year-old white male with a history of lifelong asthma.

PMID- 14692403
TI  - Case 3: assessment. A 13-year-old adolescent who has had frequent episodic asthma
      since the age of 2.

PMID- 14692404
TI  - Case 4: assessment. An adolescent aged 14 has cystic fibrosis.

PMID- 14692405
TI  - Insurance mandates and health care costs: requiring insurance companies to cover
      certain services has defendants and opponents.

PMID- 14692406
TI  - Case 5: assessment. Recurrent wheezing.

PMID- 14692407
TI  - Iodine prophylaxis: its benefits and possible side effects. Proceedings of a
      Satellite Symposium of the 27th Annual Meeting of the European Thyroid
      Association. Krakow, Poland. August 29-30, 2001.

PMID- 14692409
TI  - Abstracts of the 18th Annual International Symposium on Acupuncture and Electro
      therapeutics. New York, New York, USA. October 17-18, 2002.

PMID- 14692408
TI  - Fetal gender determination in early first trimester pregnancies of rhesus monkeys
      (Macaca mulatta) by fluorescent PCR analysis of maternal serum.
AB  - Non-human primate fetal gender determination can be a powerful tool for research
      study design and colony management purposes. The recent discovery of the presence
      of fetal DNA in maternal serum has offered a new non-invasive approach for
      identification of fetal gender. We present a rapid and simple method for the
      sexing of developing rhesus monkeys in the first trimester by polymerase chain
      reaction (PCR) analysis of maternal serum. Serum samples were obtained from 72
      gravid rhesus monkeys during 20-32 days of gestation (term 165 +/- 10 days).
      Fetal gender and the quantity of circulating fetal DNA were determined by real
      time PCR analysis of the rhesus Y-chromosomal DNA sequences. The sensitivity for
      identifying a male fetus was 100% by 30 days gestation, and no false-positive
      results were observed. This study demonstrates that fetal gender can be reliably
      determined in the early first trimester from maternal serum samples, a non
      invasive method for routine gender screening.

PMID- 14692410
TI  - A lively meeting on a deathly topic.

PMID- 14692411
TI  - Orderly dismantling of a cell.

PMID- 14692412
TI  - To ski or not to ski, that was the question.

PMID- 14692413
TI  - Perspectives in tackling medico-legal controversies. Proceedings of the
      Commonwealth Medico-Legal Conference. January, 17-19, 2003.

PMID- 14692414
TI  - Emerging molecular markers in oncology: focused therapy, indicators of response,
      chemoprevention. Proceedings of a workshop. Rovigo, Italy. September 20, 2002.

PMID- 14692415
TI  - Papers from a designated meeting of the Physiological Society on Comparative
      Neuroscience and Comparative Physiology. Preston, United Kingdom. May 2002.

PMID- 14692416
TI  - Cardio-Nephrology II: Cardio Renal anemia syndrome. Proceedings of an
      International Symposium. Berlin, Germany. November 23, 2002.

PMID- 14692417
TI  - [Congenital abnormalities in the magic of art].

PMID- 14692418
TI  - Risk management in international manned space program operations.
AB  - New, innovative joint safety policies and requirements were developed in support
      of the Shuttle/Mir program, which is the first phase of the International Space
      Station program. This work has resulted in a joint multinational analysis
      culminating in joint certification for mission readiness. For these planning and
      development efforts, each nation's risk programs and individual safety practices
      had to be integrated into a comprehensive and compatible system that reflects the
      joint nature of the endeavor. This paper highlights the major incremental steps
      involved in planning and program integration during development of the
      Shuttle/Mir program. It traces the transition from early development to
      operational status and highlights the valuable lessons learned that apply to the
      International Space Station program (Phase 2). Also examined are external and
      extraneous factors that affected mission operations and the corresponding
      solutions to ensure safe and effective Shuttle/Mir missions.

PMID- 14692419
TI  - Microbial utilisation of natural organic wastes.
AB  - The waste management strategy for the future should meet the benefits of humanity
      safety, respect principals of planet ecology, and compatibility with other
      habitability systems. For these purpose the waste management technologies,
      relevant to application of the biodegradation properties of bacteria are of great
      value. The biological treatment method is based upon the biodegradation of
      organic substances by various microorganisms. The advantage of the biodegradation
      waste management in general: it allows to diminish the volume of organic wastes,
      the biological hazard of the wastes is controlled, and this system may be
      compatible with the other systems. The objectives of our study were: to evaluate
      effectiveness of microbial biodegradation of non-pretreated substrate, to
      construct phneumoautomatic digester for organic wastes biodegradation, and to
      study microbial characteristics of active sludge samples used as inoculi in
      biodegradation experiment. The technology of vegetable wastes treatment was
      elaborated in IBMP and BMSTU. For this purpose the special unit was created where
      the degradation process is activated by enforced reinvention of portions of
      elaborated biogas into digester. This technology allows to save energy normally
      used for electromechanical agitation and to create optimal environment for
      anaerobic bacteria growth. The investigations were performed on waste simulator,
      which imitates physical and chemical content of food wastes calculated basing on
      the data on food wastes of moderate Russian city. The volume of created
      experimental sample of digester is 40 l. The basic system elements of device are
      digesters, gas receiver, remover of drops and valve monitoring and thermal
      control system. In our testing we used natural food wastes to measure basic
      parameters and time of biodegradation process. The diminution rate of organic
      gained 76% from initial mass taking part within 9 days of fermentation. The
      biogas production achieved 46 l per 1 kg of substrate. The microbial studies of
      biodegradation process revealed following peculiarities: (i) gradual quantitative
      increasing of Lactobacillus sp. (from 10(3) to 10(5) colony forming units (CFU)
      per ml), (ii) activation of Clostridia sp. (from 10(2) to 10(4)CFU/ml), (iii)
      elimination of aerobic conventional pathogens (Enterobacteriaceae sp., Protea
      sp., staphylococci). The obtained results allow to evaluate effectiveness of
      proposed technology and to determine the leading role of lactobacilli and
      clostridia in process of natural wastes biodegradation. Our further
      investigations shall further be concentrated on creation of artificial inoculi
      for launching of food wastes biodegradation. These inoculi will include active
      and adapted strains of clostridia and lactobacilli.

PMID- 14692420
TI  - Why implementing the space option is necessary for society.
AB  - For several years, specialized agencies have been searching for "new programs"
      that could reinvigorate the support for space activities and stop their budgets'
      decline of. But the same time, they have been retrenching by focusing on
      collecting and distributing information, putting scientific research as their
      core projects. On a planet soon to host a 10-billion population that will impact
      the biosphere's workings as never before, at a time when many governments and
      organizations see the virtue in the management of scarcity, musing on the origins
      of life and of the solar system can hardly be expected to be invested with high
      priority. The space option arose from the analysis of the issues confronting
      humanity. In reviewing the material needs of the human population in the near
      future, the analysis finds that the impact on the biosphere will perforce be much
      larger than it usually seems to be acceptable to assume.

PMID- 14692421
TI  - Poliovirus-1 inactivation and interaction with biofilm: a pilot-scale study.
AB  - A pilot-scale study was initiated to examine the behavior of viruses pulse
      injected into a distribution system. The influence of a free-chlorine residual
      and that of virus preadsorption to clay particles was evaluated by tracing the
      viruses both in the water flow and after elution from the biofilm. These
      experiments demonstrated, first, that virus preadsorption on 40 mg of Na
      montmorillonite per liter increased the residence time of the viruses within the
      pilot plant by roughly three times and, second, that preadsorption to clay did
      not prevent viruses from being inactivated by chlorine. Moreover, with no clay
      added, a greater amount of viruses was recovered from the biofilm than from the
      water flow (by a factor of 2 or 10 in the absence or presence of chlorine,
      respectively), indicating a tendency for virus accumulation within biofilms.

PMID- 14692422
TI  - Burning bush.

PMID- 14692423
TI  - Written information plans for patients receiving immunotherapy.

PMID- 14692424
TI  - Key pollen allergens in North America.
AB  - OBJECTIVE: To discuss major pollen aeroallergens in North America that are
      essential for effective immunotherapy and to propose a list of pollen
      aeroallergens that could be prioritized for allergen standardization. DATA
      SOURCES: PubMed was used to search the existing medical literature. No date
      restrictions were used. Keywords included allergy, aeroallergen, taxonomy, cross
      reactivity, pollen, and specific genus and species names. RESULTS: Tree species
      possess relatively unique allergens, and representative members should be chosen
      at the genus or family level. In the Composite family, there is significant cross
      reactivity between ragweed species within the Ambrosia genus. Selection of one
      species should be sufficient for skin testing and immunotherapy. Extensive
      allergenic cross-reactivity exists among grasses. Selection of timothy grass
      alone or in combination with a single northern grass species provides adequate
      coverage in the northeastern regions of North America. CONCLUSIONS: One of the
      goals within the field of allergy should be to identify high-priority targets for
      future development of standardized commercial extracts. The standardization of
      increasing numbers of allergen extracts potentially benefits the discipline of
      allergy by facilitating transfer of care among physician practices, improving
      uniformity of patient care, and providing a template on which geographically
      specific extract choices can be built.

PMID- 14692425
TI  - Subcutaneous nodules in a patient with recurrent sinopulmonary infections and
      fatigue.

PMID- 14692426
TI  - Knowledge and expectations of patients receiving aeroallergen immunotherapy.
AB  - BACKGROUND: Patients receiving aeroallergen immunotherapy frequently have poor
      knowledge and unfounded expectations of various important aspects of their
      treatment. OBJECTIVE: To evaluate patients' knowledge about the content, benefit,
      and risk related to the aeroallergen immunotherapy that they were receiving.
      METHODS: A self-administered questionnaire was distributed to all patients older
      than 16 years who had undergone aeroallergen immunotherapy for allergic rhinitis
      at 3 university-affiliated allergy clinics. RESULTS: A total of 132 patients (77
      males and 57 females; mean +/- SD age, 30 +/- 13 years) participated in the
      study. The mean +/- SD duration of treatment was 30 +/- 60 months. Complete
      recovery of their allergies was expected by 39% of the patients. One fifth of the
      study group did not know when improvement should be expected, and 18% anticipated
      improvement to occur within days or weeks from the initiation of treatment. Only
      32% were aware that immunotherapy might have some potential risk or adverse
      effects, and 24.2% failed to identify at least one of the allergens they were
      receiving. Patients who were interviewed during their first 6 months of
      aeroallergen immunotherapy had more knowledge about it than those who had been
      undergoing long-term treatment. CONCLUSIONS: There is a grave lack of knowledge
      and numerous misconceptions among substantial numbers of patients receiving
      aeroallergen immunotherapy. More educational effort is needed to increase
      patients' knowledge about immunotherapy before and during aeroallergen
      immunotherapy to improve their compliance and the success and safety of this
      therapeutic modality.

PMID- 14692427
TI  - Methods of measuring asthma severity and influence on patient assignment.
AB  - BACKGROUND: There is a need for nonclinical measures in studies where objective
      clinical data used to determine asthma severity, such as spirometry and peak
      expiratory flow rate meter readings, are not available. OBJECTIVE: To determine
      whether different methods of defining asthma severity provide different
      distributions of patients across the categories of mild, moderate, and severe
      asthma. METHODS: Data were obtained from a mail survey and the database of a
      managed care organization located in Michigan. Seven methods of asthma severity
      that used either patient self-report or claims data were evaluated and divided
      into 3 categories: patient-perceived severity (1 method), symptom-derived
      severity (4 methods), and medication-derived severity (2 methods). To further
      evaluate the extent of the degree of agreement among the 7 severity methods,
      percent agreement and Cohen K scores were calculated. RESULTS: Surveys were sent
      to 1,139 persons, and 603 responses were usable. Substantial differences exist in
      the number of patients in each severity level for different methods of
      determining asthma severity. The proportion of persons identified as having mild,
      moderate, and severe asthma ranged from 48% to 82%, 16% to 38%, and 2% to 33%,
      respectively. The percent agreement and Cohen kappa scores were generally low
      among the 7 methods. CONCLUSIONS: Due to variations caused by the method of
      measuring asthma severity, comparability among studies using different methods of
      classifying asthma severity is limited. Although a uniform evaluation of asthma
      severity is needed, the results of this study do not identify one preferable
      method. Rather, investigators should know the limitations of the methods used.

PMID- 14692428
TI  - Association of recurrent wheezing with sensitivity to cockroach allergen in inner
      city children.
AB  - BACKGROUND: There are numerous data that show a strong relationship between early
      exposure and sensitization to indoor allergens and the development of asthma and
      persistent wheezing in children. Most studies, however, have only examined the
      prevalence of allergy in children who have been identified as having asthma.
      OBJECTIVE: To assess the prevalence of positive skin test results to common
      inhaled allergens and possible association with wheezing in inner-city children
      being seen in a general pediatric clinic. METHODS: Skin testing to common
      aeroallergens was performed by the prick-puncture method. Demographic and
      clinical data were collected. RESULTS: Seventy-five children aged 2 months to 10
      years were evaluated. A total of 37% of the children had a positive skin test
      result to at least one allergen; 29% of the children were sensitive to dust mite,
      15% to cockroach, 9% to cat, 7% to mold, 4% to grass, 3% to ragweed, and 1% to
      dog. Seven (64%) of 11 children with positive skin test results to cockroach had
      a history of wheezing compared with 21 (33%) of 64 with negative skin test
      results to cockroach (P = .05). CONCLUSIONS: Our results indicate that in a
      population of inner-city children not previously identified as atopic, more than
      a third showed sensitivity to at least one allergen. Although dust mite was the
      most common allergen to which the children were sensitized, cockroach sensitivity
      was the only allergen that correlated significantly with previous episodes of
      wheezing.

PMID- 14692429
TI  - Amphotericin-induced stridor: a review of stridor, amphotericin preparations, and
      their immunoregulatory effects.
AB  - BACKGROUND: Various adverse effects have been reported with the use of
      amphotericin B. The respiratory adverse effects include dyspnea, tachypnea,
      bronchospasm, hemoptysis, and hypoxemia. Stridor has not been previously reported
      with the use of amphotericin B. OBJECTIVE: To review the mechanism of action and
      reports of respiratory adverse effects for amphotericin B, the liposomal
      preparations of amphotericin B, and the differential diagnosis of stridor. DATA
      SOURCES: A MEDLINE search from 1966 to 2002 was performed to review the current
      literature for possible mechanisms and immunoregulatory effects related to the
      infusion of amphotericin B. RESULTS: Amphotericin B has been shown to increase
      tumor necrosis factor alpha (TNF-alpha) concentrations in macrophages. In
      addition, it induces prostaglandin E2 synthesis and increases the production of
      interleukin 1beta (IL-1beta) in mononuclear cells. The immunoregulatory effects
      of amphotericin B include increases in apoptosis, production of monocyte
      chemoattractant protein 1, superoxide anion, nitric oxide, and intercellular
      adhesion molecule 1 expression. CONCLUSIONS: Amphotericin B induces the
      production of TNF-alpha, interferon-gamma, and IL-1beta, which may potentiate its
      toxic effects. Some liposomal preparations induced lower levels of TNF-alpha and
      nitric oxide and may be useful in patients unable to tolerate amphotericin B
      deoxycholate.

PMID- 14692430
TI  - The effect of budesonide on the cytokine pattern in patients with perennial
      allergic rhinitis.
AB  - BACKGROUND: A T(H)2-polarized cytokine pattern has been demonstrated in allergic
      rhinitis. Budesonide represents an effective topical corticosteroid in the
      management of allergic rhinitis. OBJECTIVE: To evaluate cytokine pattern and
      symptoms in patients with perennial allergic rhinitis before and after treatment
      with intranasal budesonide. METHODS: All patients received budesonide aqueous
      nasal spray or placebo for 2 weeks. The study was double-blind, parallel group,
      placebo controlled, and randomized. Nasal lavage was performed in all patients
      before and after treatment. A panel of cytokines, including interleukin 4 (IL-4),
      IL-5, and IL-6, was measured by immunoassay on fluids recovered from nasal
      lavage. Total symptom score (including rhinorrhea, nasal itching, sneezing, and
      nasal obstruction) was evaluated before and after treatment. RESULTS: Twenty
      patients with perennial allergic rhinitis were evaluated (13 men and 7 women;
      mean age, 24.7 years). Budesonide aqueous nasal spray treatment showed a
      significant decrease of IL-4 (P = .007), IL-5 (P = .04), and IL-6 levels (P =
      .009). Budesonide aqueous nasal spray treatment also induced significant symptom
      relief (P = .006). Placebo treatment did not significantly affect the evaluated
      parameters. CONCLUSIONS: This study shows that budesonide aqueous nasal spray is
      effective in exerting immunomodulatory activity by reducing cytokine pattern and
      relieving symptoms. These findings are evidence of the effects of intranasal
      budesonide in treating perennial allergic rhinitis.

PMID- 14692431
TI  - Elevation of plasma transforming growth factor beta1 levels in stable nonatopic
      asthma.
AB  - BACKGROUND: Increased transforming growth factor beta1 (TGF-beta1) levels have
      been reported in bronchoalveolar lavage fluid and bronchial biopsy specimens from
      asthmatic patients. However, systemic TGF-beta1 levels have not been reported in
      asthma. OBJECTIVE: To evaluate the levels of plasma TGF-beta1 in asthmatic
      patients and matched, healthy controls to determine the associations with atopic
      status, disease severity, and duration. METHODS: Asthmatic patients and healthy
      controls were recruited prospectively from a university hospital outpatient
      department between January 2001 and May 2002. Plasma TGF-beta1 and serum IgE
      levels were estimated using established methods. Patients were classified as
      atopic or nonatopic based on the presence or absence of serum specific IgE
      directed to common allergens. RESULTS: Of the 56 patients recruited for the
      study, 32 were atopic and 24 nonatopic. The median value of plasma TGF-beta1 was
      significantly higher in nonatopic asthmatic patients (2.5 ng/mL) compared with
      controls (1.5 ng/mL, P = .002) and atopic asthmatic patients (1.4 ng/mL, P =
      .008). The median absolute neutrophil count in the nonatopic asthmatic patients
      (4.0 x 10(9)/L) was significantly higher compared with atopic asthmatic patients
      (3.0 x 10(9)/L) and healthy controls (3.5 x 10(9)/L) (P = .01 and P = .04). There
      was no significant correlation between the duration or severity of asthma and
      plasma TGF-beta1 levels. The distribution of moderate-persistent asthma cases was
      similar in atopic and nonatopic groups. CONCLUSION: Compared with atopic
      asthmatic patients and healthy controls, patients with nonatopic asthma have
      elevated plasma TGF-beta1 levels and leukocytosis. These data suggest that
      nonatopic asthmatic patients exhibit an altered inflammatory response, perhaps to
      a respiratory infection.

PMID- 14692432
TI  - Prevalence of asthmatic phenotypes and bronchial hyperresponsiveness in Turkish
      schoolchildren: an International Study of Asthma and Allergies in Childhood
      (ISAAC) phase 2 study.
AB  - BACKGROUND: Numerous epidemiologic studies have revealed that bronchial asthma
      affects populations without regard to frontiers. However, standardized
      methodological approaches are necessary to compare these populations. OBJECTIVE:
      To investigate objective markers of childhood asthma on an epidemiologic basis
      and to include Turkish children in international comparisons. METHODS: Parental
      questionnaires were collected and skin prick tests performed on fourth grade
      primary schoolchildren, aged 8 to 11 years, residing in Ankara, Turkey. Pulmonary
      function tests and bronchial challenge with hypertonic saline (HS) were conducted
      in children selected from this cohort with a stratified random sampling according
      to the presence of current wheezing. RESULTS: A total of 3,041 questionnaires
      were included in the evaluation. Skin prick tests were performed on 2,774
      children (97.1%). A total of 347 children from this cohort underwent pulmonary
      function and bronchial challenge tests. In 18 (5.1%) of the 347 children,
      bronchial challenge tests could not be successfully completed. The prevalence
      values were 11.5% for current wheezing, 6.9% for physician-diagnosed asthma, and
      7.7% for physician-diagnosed recurrent bronchitis. Population-based weighted
      prevalence of bronchial hyperresponsiveness (BHR) was 21.8%. Frequency of
      responses to HS was 38.6% among physician-diagnosed asthma cases and 30.5% among
      patients with current wheezing. Skin test positivity was present in 38.7% of the
      children with a diagnosis of asthma or asthmatic bronchitis, 35.0% of current
      asthmatic patients, and 19.2% of patients with current wheezing. CONCLUSIONS:
      Objective markers, in addition to the questionnaire-based prevalence figures,
      need to be used in epidemiologic surveys for asthma, especially in countries with
      inadequate health care facilities or problems with interpretation of the wheeze
      concept.

PMID- 14692433
TI  - Identification of the major allergenic components in Blomia tropicalis and the
      relevance of the specific IgE in asthmatic patients.
AB  - BACKGROUND: Blomia tropicalis has been reported to be a clinically important
      allergen in house dust. High prevalence of sensitization to B. tropicalis has
      been noted in asthmatic patients in Taiwan; however, the allergenic components
      and its impact on asthmatic patients remain to be clarified. OBJECTIVE: To
      analyze the prevalence of IgE against B. tropicalis and each allergenic component
      in asthmatic patients. METHODS: A series of recombinant allergenic components
      were used for skin tests. The B. tropicalis specific IgE in the serum were
      measured using the Pharmacia CAP System and immunoblot analysis. RESULTS: A total
      of 131 patients were included in this study: 44% of these 131 patients were
      allergic to B. tropicalis, 43% of the 80 B. tropicalis-sensitive patients were
      allergic to Blo t 5, and 75% of the 65 Blo t 5-sensitive patients were allergic
      to Blo t 5 fragment 3 (Blo t 5 70-117). The sera IgE binding activity to B.
      tropicalis was repeatedly tested after Dermatophagoides pteronyssinus absorption,
      and results showed that most patients were concurrently sensitized to D.
      pteronyssinus and B. tropicalis. In addition, in 2 (18%) of 11 patients, the B.
      tropicalis sensitization was caused by the cross-reactivity of D. pteronyssinus.
      CONCLUSION: A high prevalence of B. tropicalis sensitization was detected in our
      asthmatic patients, and most of them were concurrently sensitized to D.
      pteronyssinus and B. tropicalis. The major allergenic component and its IgE
      binding fragments in Blo t 5 have been identified. These allergenic components
      can be used for the allergenic determination in B. tropicalis and for further
      immunotherapy.

PMID- 14692434
TI  - Recombinant birch allergens (Bet v 1 and Bet v 2) and the oral allergy syndrome
      in patients allergic to birch pollen.
AB  - BACKGROUND: IgE cross-reactivity between pollen and food allergens represents the
      molecular basis for oral allergy syndrome (OAS). OBJECTIVE: To evaluate specific
      IgE for Bet v 1 and Bet v 2 in the serum of patients sensitized to birch pollen
      and to identify whether IgE antibodies to Bet v 1 and Bet v 2 were predictors of
      OAS. METHODS: Thirty-three patients with skin prick test results and
      radioallergosorbent assay test results positive to birch pollen, 12 (36%) of whom
      had OAS symptoms, were enrolled in the study. Serum levels of specific IgE were
      determined by the fluoroenzyme immunoassay technique. RESULTS: The t test
      revealed significantly higher serum IgE levels against Bet v 1, Bet v 2, and
      birch pollen in the 12 symptomatic patients with respect to those without OAS
      (32.4 vs 12.4 kU/L, 7.6 vs 1.3 kU/L, and 42.3 vs 17.3 kU/L, respectively).
      Attempts to establish a threshold value of serum IgE antibirch pollen and the
      appearance of OAS revealed that a level of 20 kU/L or more yields an efficiency
      of the test equal to 70%. CONCLUSIONS: In our study, quantitative birch specific
      IgE level proved useful in predicting clinical allergy symptoms with birch
      exposure.

PMID- 14692435
TI  - Fig and mulberry cross-allergy.
AB  - BACKGROUND: Hypersensitivity reactions to ingestion of figs (Ficus carica) and
      mulberries (Morus nigra and Morus alba) are considered uncommon and have never
      been reported as occurring in the same patient. OBJECTIVE: To determine whether
      hypersensitivity to figs and mulberries can induce cross-allergy. METHODS: We
      describe 3 cases of associated fig and mulberry allergy in 3 patients with
      multiple sensitizations to food allergens (mostly fruit) and airborne allergens.
      The presence of specific IgE was investigated by skin prick tests and
      radioallergosorbent tests. RESULTS: The 3 patients had a convincing clinical
      history of food allergy caused by eating fresh figs, and in all 3 cases clinical
      and/or laboratory evidence of sensitization to mulberries was also collected.
      CONCLUSIONS: We reason that Ficus and Morus are closely related genera of the
      Moraceae family and speculate that hypersensitivity to figs and mulberries might
      be associated as the result of allergen cross-reactivity rather than mere
      coincidence.

PMID- 14692436
TI  - Coexistent yellow nail syndrome and selective antibody deficiency.
AB  - BACKGROUND: Yellow nail syndrome (YNS) is a rare, often underdiagnosed condition
      of unknown origin. The clinical features of the syndrome include yellow nails,
      chronic sinusitis, bronchiectasis, pleural effusion, and lymphoedema. Despite the
      frequent occurrence of upper and lower respiratory tract infections in patients
      with YNS, comprehensive analysis of their humoral immunity has not been
      previously reported. OBJECTIVE: To present the case of a patient with YNS whose
      recurrent upper and lower respiratory tract infections may have been caused by an
      underlying selective antibody deficiency that manifests as impaired IgG antibody
      response to polysaccharide antigens. METHODS: The patient underwent cultures of
      purulent sputum for Streptococcus pneumoniae and Haemophilus influenzae,
      bronchial washings for H. influenzae, and nail scrapings for fungi. Her serum
      levels of IgG, IgA, IgM, IgG subclasses, and serum titers of IgG antitetanus
      toxoid, anti-H. influenzae, and anti-S. pneumoniae antibodies were measured.
      RESULTS: Cultures of purulent sputum were positive on multiple occasions for S.
      pneumoniae and H. influenzae and bronchial washings were positive for H.
      influenzae. Nail scrapings were consistently negative for fungi. She had no
      reductions in serum levels of IgG, IgA, IgM, or IgG subclasses and had normal
      serum titers of IgG antitetanus toxoid antibodies. However, she demonstrated
      impaired IgG antibody responses following immunization with Pneumovax and an H.
      influenza B vaccine. CONCLUSIONS: This case report describes the first
      comprehensive analysis of humoral immune function in a patient with YNS. The
      finding of a selective antibody deficiency in our patient provides a potential
      explanation for the occurrence of respiratory infections in YNS. Accordingly, we
      recommend that functional antibody determinations and quantitative serum
      immunoglobulins be evaluated in patients diagnosed as having this unusual,
      enigmatic syndrome.

PMID- 14692437
TI  - Severe T- and B-cell immune deficiency associated with malignant thymoma.
AB  - BACKGROUND: Immunodeficiency with thymoma syndrome is a rare disorder that
      generally occurs after the fourth decade of life. Typically, thymic tumors are
      benign, and gradually developing immunodeficiency consists of
      hypogammaglobulinemia with low B-cell counts and an inverted CD4+/CD8+ T-cell
      ratio due to excessive CD8+ T cells. OBJECTIVE: To report the case of a 32-year
      old, white man with an invasive malignant thymoma and profound combined T- and B
      cell immunodeficiency associated with a normal CD4+/CD8+ T-cell ratio, absence of
      circulating B cells, and infection with an unusual organism. METHODS: The patient
      presented with a superior vena cava syndrome caused by a malignant thymoma.
      During chemotherapy and radiotherapy, he experienced recurrent episodes of
      pulmonary infections due to Haemophilus influenza and Serratia marcescens and
      persistent oral thrush. He was diagnosed as having thymoma and underwent
      immunological evaluation. RESULTS: Sixteen months after the diagnosis of thymoma,
      the immunological evaluation revealed profound lymphopenia, eosinopenia, very low
      counts of both CD4+ T cells and CD8+ T cells, and a normal CD4+/CD8+ ratio with
      negative delayed-type hypersensitivity skin test results. Hypogammaglobulinemia
      and absent specific antibody responses were associated with a lack of peripheral
      blood CD19+ B cells. Despite treatment with intravenous immunoglobulin, the
      patient died of respiratory insufficiency and sepsis secondary to a chronic
      pulmonary infection. CONCLUSIONS: Malignant thymoma may be associated with severe
      combined immunodeficiency. A normal CD4+/CD8+ ratio and the absence of peripheral
      B cells suggest a bone marrow defect that affects both T and B cells in the
      pathogenesis of this syndrome. Comprehensive immunological evaluation should be
      performed when thymoma is diagnosed to initiate an early and effective treatment
      to prevent life-threatening complications.

PMID- 14692438
TI  - Pilot studies: one swallow does not make a summer...
AB  - What should we expect from pilot studies, done in small series of patients? In
      the literature there are many examples of small studies with very promising
      results, that in subsequent larger or better controlled studies proved to be much
      less promising, or even disastrous. In some instances the initial favourable
      outcome was due to selection bias. In others the use of nonvalidated methods of
      measuring outcome made the reproducibility of promising observations problematic.
      However, we have to start somewhere. In ths issue The et al. report favourable
      results of granisetron treatment in four out of five patients with chronic
      fatigue syndrome. A prospective, randomised, placebo-controlled, double-blind
      clinical trial with granisetron in patients with chronic fatigue syndrome is now
      ongoing.

PMID- 14692439
TI  - Endothelial activation, endothelial dysfunction and premature atherosclerosis in
      systemic autoimmune diseases.
AB  - Atherosclerosis may be considered an inflammatory disease characterised by the
      development of atherosclerotic plaques and ischaemic cardiovascular events.
      Increased prevalence of cardiovascular morbidity and mortality due to (premature)
      atherosclerosis has been observed in patients with autoimmune diseases like
      rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Wegener's
      granolumatosis. This increased prevalence cannot be explained by the presence of
      the traditional cardiovascular risk factors such as hypertension,
      hyperlipidaemia, diabetes mellitus and smoking. Therefore, other risk factors
      must be present in patients with systemic autoimmune disease. Although the
      mechanisms have not been fully unravelled, endothelial cell (EC) activation
      through autoantibodies seems to be one of the factors involved. EC activation
      results in EC dysfunction. It is supposed that chronic EC dysfunction, as present
      in patients with systemic autoimmune disorders, contributes to the development of
      premature atherosclerosis and results in an increased prevalence of
      cardiovascular disease.

PMID- 14692440
TI  - New developments in staging and follow-up of patients with Hodgkin's lymphoma.
AB  - Adequate staging of newly diagnosed patients with Hodgkin's lymphoma enables
      optimal treatment planning, which is of particular importance for finding a
      balance between treatment efficacy and toxicity. In this review an overview is
      given of the current knowledge on initial staging and the role of imaging
      modalities during and after treatment. A promising new tool is whole-body
      positron emission tomograpy (PET) scanning with fluorodeoxyglucose (FDG). This
      modality is particularly useful for the evaluation of a residual mass at the end
      of treatment and for the assessment of the prognostically relevant 'early
      response' to chemotherapy. Although high survival rates have been reported for
      patients treated within the context of clinical trials these rates are generally
      lower in population-based series. In the general population comorbidity is
      present in half of all elderly Hodgkin patients. Since comorbidity has great
      impact on treatment planning and survival, this prognostic factor should be taken
      into account in future trials.

PMID- 14692441
TI  - The effect of granisetron, a 5-HT3 receptor antagonist, in the treatment of
      chronic fatigue syndrome patients--a pilot study.
AB  - OBJECTIVE: To explore the effect of granisetron, a 5-HT3 antagonist, on fatigue
      and functional impairment in patients with chronic fatigue syndrome (CFS).
      METHODS: Five female patients were eligible to receive oral granisetron for one
      month (1 mg a day for the first two weeks and 2 mg a day for the second two
      weeks). The patients had to be between 18 and 65 years of age and suffering from
      CFS according to the CDC criteria. The effect was assessed by pre- and post
      testing, using validated instruments designed to assess the different dimensions
      of CFS. Treatment response was also evaluated by visual analogue scales (VAS) for
      fatigue. Analysis was based on intention to treat. RESULTS: Treatment with
      granisetron resulted in significant improvement in fatigue severity and
      functional impairment. Activity level showed no significant increase. CONCLUSION:
      The promising results of this study have encouraged us to perform a placebo
      controlled, double-blind study to evaluate the efficacy of 5-HT3 receptor
      antagonists in the treatment of CFS.

PMID- 14692442
TI  - A woman with a swollen, erythematous and tender thigh.

PMID- 14692443
TI  - Two Dutch families with hereditary hyperferritinaemia-cataract syndrome and
      heterozygosity for an HFE-related haemochromatosis gene mutation.
AB  - Hereditary haemochromatosis is an autosomal recessive disorder, leading to
      progressive iron overload, which is very common among the Caucasian population.
      In the vast majority of the cases, the hereditary iron overload is caused by
      mutations in the HFE gene. Most prominently this is the homozygous Cys282Tyr
      mutation. We report two Dutch families in which both propositi were found to be
      heterozygous for Cys282Tyr in the work-up of hyperferritinaemia. Frequent
      phlebotomies had no effect on the ferritin level, but led to microcytic anaemia.
      Finally, the family history with bilateral cataracts was the clue for the correct
      diagnosis. Hereditary hyperferritinaemia-cataract syndrome (HHCS) is an autosomal
      dominant disease characterised by elevated serum ferritin levels and bilateral
      cataracts in the absence of iron overload. Several point mutations and deletions
      within the iron-responsive element (IRE) in the 5' noncoding region of the L
      ferritin gene have been found in HHCS families. In the first Dutch family a G to
      C transition at position 32 was found and a G to A mutation at the same location
      was found in the second Dutch family. In individuals with an isolated
      hyperferritinaemia (normal transferrin saturation), the presence of early onset
      (familial) cataract should raise the possibility of HHCS, even when Cys282Tyr
      heterozygosity is found.

PMID- 14692444
TI  - PTU-associated cutaneous vasculitis with ANCA anti-MPO and anti-PR3 antibodies.
AB  - A 36-year-old woman presented at our clinic with symmetrical, tender, palpable
      purpuric lesions on her lower legs and buttocks after restarting PTU therapy for
      relapsing Graves' disease. PTU-induced vasculitis was diagnosed with remarkable
      ANCA anti-MPO and anti-PR3 antibody positivity. The purpuric skin lesions
      resolved immediately after discontinuation of the drug and the ANCA titres
      lowered. In the presence of activated neutrophils, PTU could induce a high
      cytotoxity and injure the vessel walls. Treatment of choice is discontinuation of
      the drug. Sometimes more aggressive therapy as cyclophosphamide or plasmapheresis
      is warranted.

PMID- 14692445
TI  - Antinucleair antibody (ANA) positivity caused by paraneoplastic antibodies due to
      abundant p53 expression in early hepatic carcinoma.
AB  - A 51-year-old patient is described who presented with locomotor pain and highly
      significant positive ANA due to p53 antibodies, which appeared to be associated
      with primary hepatic carcinoma.

PMID- 14692446
TI  - Chloride channels in basolateral TAL membranes. XVIII. Phenylglyoxal induces
      functional mcCIC-Ka activity in basolateral MTAL membranes.
AB  - Cultured mouse MTAL cells contain more mRNA encoding the Cl- channel mcCIC-Ka,
      which mediates CTAL Cl- absorption, than mRNA encoding the Cl- channel mmCIC-Ka,
      which mediates MTAL Cl- absorption. mmCIC-Ka and mcCIC-Ka have three functional
      differences: 1) mmCIC-Ka open time probability, Po, increases with increasing
      cytosolic Cl-, but variations in cytosolic Cl- do not affect Po in mcCIC-Ka; 2)
      mmCIC-Ka is gated by (ATP + PKA), while (ATP + PKA) have no effect on Po in mcCIC
      Ka; and 3) mmCIC-Ka channels have single-ion occupancy, while mcCIC-Ka channels
      have multi-ion occupancy. Using basolateral vesicles from MTAL cells fused into
      bilayers, we evaluated the effects of 1 mM cytosolic phenylglyoxal (PGO), which
      binds covalently to lysine or arginine, on Cl- channels. With PGO pretreatment,
      Cl- channels were uniformly not gated either with increases in cytosolic-face Cl-
      or with (ATP + PKA) at 2 mM cytosolic-face Cl-; and they exhibited multi-ion
      occupancy kinetics typical for mcCIC-Ka channels. Thus, in basolateral MTAL
      membranes, blockade of Cl- access to arginine or lysine residues on mmCIC-Ka by
      PGO results in Cl- channels having the functional characteristics of mcCIC-Ka
      channels.

PMID- 14692447
TI  - Cl- channels in basolateral TAL membranes. XIX. Cytosolic Cl- regulates mmCIC-Ka
      and mcCIC-Ka channels.
AB  - We evaluated the effects of culturing mouse MTAL cells under conditions that
      suppressed steady-state cytosolic Cl- on chloride channels fused into bilayers
      from basolateral vesicles of cultured MTAL cells. We used two agents to suppress
      Cl- entry: 10(-6) M PGE2 and 10(-4) M bumetanide. Basolateral Cl- channels from
      control cultured MTAL cells exhibited the signature characteristics of mmCIC-Ka
      channels: increased open-time probability (Po) either by raising cytosolic-face
      [Cl-] or, at 2 mM cytosolic Cl-, by adding (ATP + PKA), and first-order
      conductance kinetics. Either 10(-6) M PGE2 or 10(-4) M bumetanide in culture
      media reduced steady-state MTAL cytosolic Cl-. Chloride channels from these cells
      exhibited characteristics unique to CTAL mcCIC-Ka channels, namely: no
      augmentation of Po either by raising cytosolic Cl- or with cytosolic (ATP + PKA),
      and multi-ion occupancy. Semi-quantitative RT-PCR and real-time quantitative PCR
      showed that culturing MTAL cells with 10(-6) M PGE2 or 10(-4) M bumetanide
      reduced mRNA levels encoding mmCIC-Ka but not mRNA levels encoding mcCIC-Ka.
      However, when MTAL cells were cultured under control conditions, and then pre
      incubated for 60 minutes with 10(-4) M bumetanide, cytosolic Cl- fell acutely but
      Cl- channels exhibited characteristics of mmCIC-Ka channels. Thus PGE2 and
      bumetanide, both of which lower steady-state MTAL cytosolic Cl- concentrations,
      inhibit either the transcriptional and/or the translational processes for mmCIC
      Ka synthesis.

PMID- 14692448
TI  - K+-induced Ca2+ conductance responsible for the prolonged backward swimming in K+
      agitated mutant of Paramecium caudatum.
AB  - The K+-agitated (Kag) mutant of Paramecium caudatum shows prolonged backward
      swimming in K+-rich solution. To understand the regulation mechanisms of the
      ciliary motility in P. caudatum, we examined the membrane electrical properties
      of the Kag mutant. The duration of the backward swimming of the Kag in K+-rich
      solution was about 10 times longer than that of the wild type. In response to an
      injection of the outward current, the wild type produced an initial action
      potential and a subsequent membrane depolarization due to I-R potential drop,
      while the Kag exhibited repetitive action potentials during the depolarization.
      Under voltage-clamp conditions, the depolarization-activated transient inward
      current exhibited by the Kag was slightly smaller than that exhibited by the wild
      type. In response to an application of K+-rich solution, both the wild type and
      the Kag exhibited a depolarizing afterpotential representing the activation of
      the K+-induced Ca2+ conductance. The inactivation time course of the K+-induced
      Ca2+ conductance of Kag was about 10 times longer than that of the wild type.
      This difference corresponds well with the difference in behavioral responses
      between Kag and wild type to K+-rich solution. We conclude that the overreaction
      of the Kag mutant to the K+-rich solution is caused by slowing down of the
      inactivation of the K+-induced Ca2+ conductance.

PMID- 14692449
TI  - Identification of ion-selectivity determinants in heavy-metal transport P1B-type
      ATPases.
AB  - P1B-type ATPases transport a variety of metals (Cd2+, Zn2+, Pb2+, Co2+, Cu2+,
      Ag+, Cu+) across biomembranes. Characteristic sequences CP[C/H/S] in
      transmembrane fragment H6 were observed in the putative transporting metal site
      of the founding members of this subfamily (initially named CPx-ATPases). In spite
      of their importance for metal homeostasis and biotolerance, their mechanisms of
      ion selectivity are not understood. Studies of better-characterized P(II)-type
      ATPases (Ca-ATPase and Na,K-ATPase) have identified three transmembrane segments
      that participate in ion binding and transport. Testing the hypothesis that metal
      specificity is determined by conserved amino acids located in the equivalent
      transmembrane segments of P1B-type ATPases (H6, H7, and H8), 234 P1B-ATPase
      protein sequences were analyzed. This showed that although H6 contains
      characteristic CPX or XPC sequences, conserved amino acids in H7 and H8 provide
      signature sequences that predict the metal selectivity in each of five P1B-ATPase
      subgroups identified. These invariant amino acids contain diverse side chains
      (thiol, hydroxyl, carbonyl, amide, imidazolium) that can participate in transient
      metal coordination during transport and consequently determine the particular
      metal selectivity of each enzyme. Each subgroup shares additional structural
      characteristics such as the presence (or absence) of particular amino-terminal
      metal-binding domains and the number of putative transmembrane segments. These
      differences suggest unique functional characteristics for each subgroup in
      addition to their particular metal specificity.

PMID- 14692450
TI  - Transinhibition and voltage-gating in a fungal nitrate transporter.
AB  - We have applied enzyme kinetic analysis to electrophysiological steady-state data
      of Zhou et al. (Zhou, J.J., Trueman, L.J., Boorer, K.J., Theodoulou, F.L., Forde,
      B.G., Miller, A.J. 2000. A high-affinity fungal nitrate carrier with two
      transport mechanisms. J. Biol. Chem. 275:39894-9) and to new current-voltage-time
      records from Xenopus oocytes with functionally expressed NrtA (crnA) 2H+-NO3-
      symporter from Emericella (Aspergillus) nidulans. Zhou et al. stressed two
      Michaelis-Menten (MM) mechanisms to mediate the observed nitrate-induced
      currents, I(NO3-). We show that a single straightforward reaction cycle describes
      the data well, pointing out that during exposure to external substrate, S = (2H+
      + NO3-)o, the product concentration inside, [P] = [H+]i(2) x [NO3-]i, may rise
      substantially near the plasma membrane, violating the condition [P] << [S] for MM
      kinetics. Here, [P] and its changes during experimentation are treated
      explicitly. K(1/2) approximately 20 microM for I(NO3-) at pHo from Zhou et al. is
      confirmed. According to our analysis, NrtA operates between about 0.2 and 0.6 of
      the electrical distance in the membrane (outside 0, inside 1). In absence of
      thermodynamic gradients, the predominant orientation of the binding site(s) is
      probably inwards. The activity of the enzyme is sensitive to the transmembrane
      voltage, V, with an apparent gating charge of +1.0 +/- 0.5 for inactivation, and
      transition probabilities of 0.3-1.3 s(-1) at V = 0. This gating mode impedes loss
      of cellular NO3- during depolarization.

PMID- 14692451
TI  - Structural analysis of 2D-gel-separated glycoproteins from human cerebrospinal
      fluid by tandem high-resolution mass spectrometry.
AB  - The feasibility of global glycoprotein analysis by electrospray ionization
      Fourier transform ion cyclotron resonance mass spectrometry and infrared
      multiphoton dissociation (IRMPD) tandem mass spectrometry is demonstrated.
      Combined 2D gel glycoprotein separation and visualization, in-gel digestion, and
      accurate (<10 ppm) mass measurement allowed identification of human glycoproteins
      and revealed differences in glycosylation. IRMPD obviates the need for glycan
      release, which prevents sample dispersal, and allows the assignment of glycan
      structures to specific sites of N-glycosylation.

PMID- 14692452
TI  - Nanoflow LC/ion mobility/CID/TOF for proteomics: analysis of a human urinary
      proteome.
AB  - A prototype linear octopole ion trap/ion mobility/tandem mass spectrometer has
      been coupled with a nanoflow liquid chromatography separation approach and used
      to separate and characterize a complicated peptide mixture from digestion of
      soluble proteins extracted from human urine. In this approach, two dimensions of
      separation (nanoflow liquid chromatography and ion mobility) are followed by
      collision induced dissociation (CID) and mass spectrometry (MS) analysis. From a
      preliminary analysis of the most intense CID-MS features in a part of the
      dataset, it is possible to assign 27 peptide ions which correspond to 13
      proteins. The data contain many additional CID-MS features for less intense ions.
      A limited discussion of these features and their potential utility in identifying
      complicated peptide mixtures required for proteomics study is presented.

PMID- 14692453
TI  - Isolation of N-terminal protein sequence tags from cyanogen bromide cleaved
      proteins as a novel approach to investigate hydrophobic proteins.
AB  - A novel method for the isolation of protein sequence tags to identify proteins in
      a complex mixture of hydrophobic proteins is described. The PST (Protein Sequence
      Tag) technology deals with the isolation and MS/MS based identification of one N
      terminal peptide from each polypeptide fragment generated by cyanogen bromide
      cleavage of a mixture of proteins. PST sampling takes place after sub-cellular
      fractionation of a complex protein mixture to give enrichment of mitochondrial
      proteins. The method presented here combines effective sample preparation with a
      novel peptide isolation protocol involving chemical and enzymatic cleavage of
      proteins coupled to chemical labeling and selective capture procedures. The
      overall process has been very successful for the analysis of complex mixtures of
      hydrophobic proteins, particularly membrane proteins. This method substantially
      reduces the complexity of a protein digest by "sampling" the peptides present in
      the digest. The sampled digest is amenable to analysis by liquid chromatography
      tandem mass spectrometry (LC-MS/MS). Methods of "sampling" protein digests have
      great value' if they can provide sufficient information to identify substantially
      all of the proteins in the sample while reducing the complexity of the sample to
      maximize the efficient usage of LC-MS/MS capacity. The validity of the process is
      demonstrated for mitochondrial samples from S. cerevisiae. The proteins
      identified by the PST technology are compared to the proteins identified by the
      conventional technology 2-D gel electrophoresis as a control.

PMID- 14692454
TI  - Direct atmospheric pressure coupling of polyacrylamide gel electrophoresis to
      mass spectrometry for rapid protein sequence analysis.
AB  - Using laser desorption-atmospheric pressure chemical ionization we describe a
      novel approach for coupling mass spectrometry to polyacrylamide gel
      electrophoresis. In contrast to other approaches, the method allows for the
      direct sampling of a polyacrylamide gel-embedded protein without the addition of
      any exogenous matrixes and is performed at atmospheric pressure. After
      electrophoresis and enzymatic digestion, the gel is analyzed at AP by photons
      that desorb neutral peptide molecules, followed by corona discharge ionization in
      the gas-phase, and subsequent mass analysis. Our experimental results demonstrate
      the method to (1) rapidly identify electrophoresed proteins via "peptide
      fingerprinting" using protein databases, (2) detect single-amino acid
      polymorphisms, and (3) has potential for sub-picomole sensitivity while still
      maintaining in situ gel desorption-ionization at ambient conditions.

PMID- 14692455
TI  - Comparative proteomics of glycoproteins based on lectin selection and isotope
      coding.
AB  - Lectins have been widely used in glycan structure analysis. The studies described
      here exploit this fact to select glycopeptides carrying disease-associated
      modifications in their oligosaccharides. Coupling lectin affinity selection with
      recent advances in stable isotope coding for quantitative proteomics allowed a
      comparative proteomics method to be developed for examining aberrant
      glycosylation in cancer. Control and experimental samples were individually
      tryptic digested and differentially coded with stable isotope coding agents
      before they were mixed and affinity selected with a lectin affinity
      chromatography column. Glycopeptides carrying an alpha-L-fucose residue were
      selected with Lotus tetragonolobus agglutinin (LTA) immobilized on a
      chromatography matrix. Because the oligosaccharides of glycoproteins are
      generally heterogeneous and often of unknown structure, it was necessary to
      deglycosylate the selected peptides with PNGase F before they could be compared
      to sequences in DNA and protein databases. After deglycosylated peptides were
      transferred to a reversed phase chromatography (RPC) column and fractionated by
      gradient elution with increasing amounts of acetonitrile. The RPC fractions were
      then analyzed by both matrix-assisted laser desorption ionization mass
      spectrometry (MALDI-MS) and electrospray ionization mass spectrometry (ESI-MS).
      When this method was applied to a study of lymphosarcoma in canines, it was found
      that during chemotherapy, a series of fucosylated proteins in the blood of
      patients decreased in concentration more than 2-fold. Two of the proteins
      identified, CD44 and E-selectin, are known to be involved in cell adhesion and
      cancer cell migration. The observed aberrant fucosylation of these proteins is
      consistent with the hypothesis that CD44 and E-selectin play a key role in
      metastasis and the spread of cancer cells to remote sites.

PMID- 14692456
TI  - Genome-wide profile of oxidoreductases in viruses, prokaryotes, and eukaryotes.
AB  - Enzymes that utilize nicotinamide adenine dinucleotide (NAD) or its 2'-phosphate
      derivative (NADP) are found throughout the kingdoms of life. These enzymes are
      fundamental to many biochemical pathways, including central intermediary
      metabolism and mechanisms for cell survival and defense. The complete genomes of
      25 organisms representing bacteria, protists, fungi, plants, and animals, and 811
      viruses, were mined to identify and classify NAD(P)-dependent enzymes. An average
      of 3.4% of the proteins in these genomes was categorized as NAD(P)-utilizing
      proteins, with highest prevalence in the medium-chain oxidoreductase and short
      chain oxidoreductase families. In general, the distribution of these enzymes by
      oxidoreductase family was correlated to the number of different catalytic
      mechanisms in each family. Organisms with smaller genomes encoded a larger
      proportion of NAD(P)-dependent enzymes in their proteome (approximately 6%) as
      compared to the larger genomes of eukaryotes (approximately 3%). Among viruses,
      those with large, double-strand DNA genomes were shown to encode oxidoreductases.
      Gram-positive and gram-negative bacteria showed some differences in the
      distribution of NAD(P)-dependent proteins. Several organisms such as M.
      tuberculosis, P. falciparum, and A. thaliana showed unique distributions of
      oxidoreductases corresponding to some phenotypic features.

PMID- 14692457
TI  - Applications of monolithic silica capillary columns in proteomics.
AB  - The use and applicability of silica based capillary monolithic reversed-phase
      columns in proteomic analysis has been evaluated by liquid chromatography-mass
      spectrometry (LC-MS). Chromatographic performance of the monolithic capillaries
      was evaluated with a tryptic digest of cytochrome C showing very good resolution
      and reproducibility in addition to the known advantages of a low pressure drop
      over a time period of 6 months. Monoliths were subsequently tested for their
      suitability to separate proteins and peptides from samples typically encountered
      in proteomic research such as in-gel digested tryptic peptide mixtures or
      fractions of proteolytically digested human serum. The monolithic capillaries
      also proved useful in the analysis of phospholipid species in bronchoalveolar
      lavage fluid. Compared to particle-filled conventional capillary columns, rapid
      and highly efficient separation of peptides and proteins was achieved using these
      bimodal pore size distribution columns, and good quality collision induced
      dissociation (CID) mass spectra were obtained on an ion trap mass spectrometer.
      These novel monolithic separation media are thus a promising addition to the
      methodological toolbox of proteomics research.

PMID- 14692458
TI  - Changes in the protein expression of yeast as a function of carbon source.
AB  - Protein expression trends in yeast were monitored as a function of carbon source
      (glucose versus galactose) using multidimensional high performance liquid
      chromatography (HPLC) coupled to gas-phase fractionation, using relative
      intensity triggering (GPFri). Size exclusion HPLC was used to separate whole cell
      lysates, and following proteolysis of these fractions, each was separated by
      reversed phase HPLC, which was coupled on-line via electrospray to an ion trap
      mass spectrometer. The GPFri technique increased the dynamic range of proteins
      detected by increasing the number of peptide ions subjected to low energy
      collision induced dissociation to the 24 most intense ions in each of the survey
      scans. No protein or peptide labeling was used; instead, the number of SEQUEST
      identifications for each peptide (previously termed "hits") were used as a
      semiquantitative means of assessing both the direction (increase vs decrease) and
      significance of change in protein abundance. None of the traditional SEQUEST
      filters, e.g., Xcorr, DelCn, Sp, Rsp, etc., were employed in this study. Instead,
      a Student's t-test was used to distinguish those proteins that significantly and
      reproducibly changed between carbon sources from those that did not. This relied
      on the SEQUEST misassignments occurring in equal proportion between treatments
      and thereby negating each other; statistically significant changes in SEQUEST
      assignments were nonrandom events by definition and therefore reflective of
      correct identifications. This method of data analysis showed a large degree of
      concordance with results reported by other groups in similar transcriptional
      profiling and proteomic experiments. In all, 176 and 231 (fold-change > or = 1.1;
      p < or = 0.05) proteins were identified as being increased in peptide hit number
      when the yeast cells' source of carbon was changed between glucose and galactose,
      respectively.

PMID- 14692459
TI  - From precursor to final peptides: a statistical sequence-based approach to
      predicting prohormone processing.
AB  - Predicting the final neuropeptide products from neuropeptides genes has been
      problematic because of the large number of enzymes responsible for their
      processing. The basic processing of 22 Aplysia californica prohormones
      representing 750 cleavage sites have been analyzed and statistically modeled
      using binary logistic regression analyses. Two models are presented that predict
      cleavage probabilities at basic residues based on prohormone sequence. The
      complex model has a correct classification rate of 97%, a sensitivity of 97%, and
      a specificity of 96% when tested on the Aplysia dataset.

PMID- 14692460
TI  - Implementation of an algorithm for modeling disulfide bond patterns using mass
      spectrometry.
AB  - The paper describes the implementation of a software system based on the Fenyo
      disulfide bond assignment algorithm. The system allows an investigator to enter
      data derived from mass spectrum peak assignments, a target protein sequence and
      other experimental conditions. The output of the system is the set of disulfide
      bonding pattern models that are consistent with the experimental evidence. The
      software and code are available through a public web site, which also has a
      functioning, publicly accessible version of the disulfide bond modeler. This
      implementation was tested as part of a project to check homology-based
      assignments disulfide bonding patterns of human integrins.

PMID- 14692461
TI  - Automating gel image acquisition.
AB  - We describe the design and implementation of a robotic solution to automate the
      acquisition of gel images. The soft- and hardware aspects are outlined together
      with the various safety aspects that need to be addressed.

PMID- 14692462
TI  - Peripheral neuropathy and light-preliminary report indicating prevalence of
      nanobacteria in HIV.
AB  - Peripheral neuropathy is a common condition in HIV-positive patients and is often
      experienced in diabetes mellitus. The primary mechanism of the disease, which can
      considerably aggravate the patient's state, is unknown. The perineurium of
      patients with peripheral neuropathy is frequently enveloped by apatite.
      Nanobacteria (NB) are protectd by a mineral shell consisting of apatite. Light
      has been shown to elevate the vitality level of cells, and was predicted to
      inhibit deposition of stressed NB in the cardiovascular system. Results indicate
      that light can durably restore the condition of patients with severe peripheral
      neuropathy.

PMID- 14692463
TI  - Unexpected syncope and death during intense physical training: evolving role of
      molecular genetics.
AB  - Special operations forces (SOF) undergo an unparalleled degree of physical
      training. The medical officer responsible for these personnel must often deal
      with episodes of syncope that cannot be readily explained. In the past, loss of
      consciousness during heavy physical exertion was attributed to inadequate fluid
      intake resulting in dehydration or abnormalities in temperature regulation.
      However, many of those diagnoses, in retrospect were probably incorrect. The
      occurrence of exercise-related syncope in multiple members of the same family
      suggested that there could be a genetic basis for the unexpected loss of
      consciousness during exercise. Intensive clinical examinations of these patients,
      coupled with current advances in molecular genetics, have shown this to be the
      case. We review some of the more common genetic abnormalities associated with
      exertion-related syncope. These syndromes should be considered by the medical
      officer presented with a patient having syncope of indeterminate cause.

PMID- 14692464
TI  - Exercise in hot and cold environments: differential effects on leukocyte number
      and NK cell activity.
AB  - INTRODUCTION: Exercise and environmental temperature have been reported to affect
      the immune system, but few studies have examined the combined effects of very hot
      or cold temperatures during exercise in the same group of subjects. Therefore,
      the purpose was to examine the immune responses following exercise combined with
      exposure to hot and cold environments. METHODS: There were 10 men who completed 2
      60-min cycle ergometry (60% VO2peak) trials: hot (HT: 38 degrees C, 45% RH) and
      cold (CD: 8 degrees C, 50% RH). Rectal core temperatures (Tc), average skin
      temperatures (Tsk), and HR were recorded every 15 min of exercise. Venous blood
      was collected before (PRE), immediately after (POST), 2 h after (2 h), and 24 h
      after exercise (24 h). Physiologic strain index (PSI) was calculated. Total and
      differential leukocytes were determined by manual counting (adjusted for plasma
      volume shifts). Natural killer cell activity (NKCA) was determined by a whole
      blood 51Cr-release assay. RESULTS: Tsk, Tc, and PSI were significantly lower in
      the CD than HT trial (p < 0.05). Total leukocyte count was greater POST (40%) and
      2 h (74%) than PRE and 24 h in both conditions (p < 0.05). Neutrophil count was
      greater POST (49%) and 2 h (132%) than PRE and 24 h in both conditions (p <
      0.05). Lymphocyte count was greater POST (24%) in HT than CD (p < 0.05). NKCA was
      greater POST (38%) than PRE, 2 h, and 24 h in both conditions (p < 0.05). HT
      caused significant increases for Tc and Tsk above those observed for CD (p <
      0.05). PSI was greater in HT (9.92 +/- 0.93) than CD (4.24 +/- 0.56) (p < 0.05).
      DISCUSSION: Exercise in HT produced more physiological stress than CD; however,
      this difference was not manifested in the immune system response. Heat and cold
      stress in combination with exercise produce similar disturbances in immunity
      during recovery from exercise.

PMID- 14692465
TI  - Baroreflex control of heart rate during heating in subjects with low orthostatic
      tolerance.
AB  - BACKGROUND: Heat stress induces a reduction of orthostatic tolerance. The
      cardiovascular responses, including the cardiac baroreflex response to heat
      stress, were examined to test the hypothesis that subjects with orthostatically
      low tolerance demonstrate an impaired baroreflex control of heart rate (HR)
      during heat stress. METHODS: There were 44 healthy young volunteers who underwent
      whole body heat stress produced by a hot-water-perfused suit during supine rest
      for 45 min and 75 degrees head-up tilt (HUT) for 6 min. Esophageal temperature,
      HR, arterial pressure, and skin blood flow in the forearm and palm were measured
      continuously throughout the experiment. The sensitivity of the arterial
      baroreflex control of HR was calculated from the spontaneous changes in beat-to
      beat arterial pressure and HR. RESULTS: The HUT was uneventful for 22 volunteers
      (higher tolerance group), but 22 volunteers (lower tolerance group) reached
      presyncope after 195 +/- 19 s. Esophageal temperature, HR, arterial pressure, and
      skin blood flow changed similarly in the two groups during heating. In the
      preheating condition, the sensitivity of the baroreflex control of HR did not
      differ significantly between the two groups. Heating did not alter the
      sensitivity of baroreflex control of HR in the higher tolerance group, but
      decreased it significantly in the lower tolerance group. Heating increased the
      number of heartbeats used for analysis of the baroreflex sensitivity in the
      higher tolerance group, but did not change it in the lower tolerance group.
      CONCLUSIONS: These results suggest that the impairment of vagal baroreflex
      control of HR during heat exposure aggravates the orthostatic intolerance in heat
      stressed humans.

PMID- 14692466
TI  - Staged decompression to 3.5 psi using argon-oxygen and 100% oxygen breathing
      mixtures.
AB  - INTRODUCTION: The current extravehicular activity (EVA) space suit at 4.3 psia
      causes hand and arm fatigue and is too heavy for Martian EVA. A 3.5 psia EVA
      pressure suit requires increased preoxygenation time but would reduce structural
      complexity, leak rate, and weight while increasing mobility, comfort, and
      maintainability. On Mars, nitrogen and argon are available to provide the inert
      gas necessary for a fire-resistant habitat atmosphere, eliminating need for
      transport. This study investigated breathing argon/oxygen and 100% oxygen gas
      mixtures during staged decompression prior to exposure to 3.5 psia. METHOD:
      During this study, 40 subjects each completed 3 hypobaric exposures to 3.5 psia
      for 3 h in a reclined position: (A) a 4-h 25-min 14.7-psia (ground level)
      denitrogenation (100% oxygen breathing) prior to exposure to 3.5 psia; (B) the
      same as A, utilizing a 7.3-psia stage denitrogenation; and (C) the same as B,
      with 62% argon-38% oxygen (ARGOX) during the stage. Venous gas emboli (VGE) were
      monitored with echocardiography. RESULTS: Decompression sickness (DCS) incidence
      at 3.5 psia with ARGOX at 7.3 psia (C) was significantly higher than with oxygen
      breathing with or without staged decompression: there was 78% DCS for C compared
      with 33% and 55% DCS, respectively, for A and B. The corresponding VGE incidences
      were 73% (C) compared with 33% (A) and 45% (B). CONCLUSION: Preoxygenation at a
      7.3-psia stage resulted in a higher DCS risk at 3.5 psia than ground level
      preoxygenation. It is suggested that an 8.0-psia stage pressure could eliminate
      this difference. Unfavorable results after preoxygenation with ARGOX indicate
      argon on-gassing was significant.

PMID- 14692467
TI  - Effect of hypobaric hypoxia on auditory sensitivity.
AB  - INTRODUCTION: Previous studies on the effect of hypobaric hypoxia on auditory
      sensitivity are not readily interpretable, in most cases because the potential
      effect of ambient pressure on stimulus level was not considered. In this study,
      auditory sensitivity to 1, 8, 12, and 16 kHz tones was compared between
      conditions of hypoxia and normoxia at the same simulated altitude (3700 m).
      METHOD: In the hypoxic condition, the partial pressure of oxygen in the inspired
      air was allowed to decrease with increasing altitude. In the normoxic condition,
      the partial pressure of oxygen was maintained at a level equivalent to that
      experienced at mean sea level (MSL). This comparison also controlled for any
      effect resulting from physiological consequences of hypobaria other than hypoxia
      (such as a change in middle-ear impedance). RESULTS: A small (2.57 dB) reduction
      in sensitivity across the frequency range tested was observed. CONCLUSION: A
      reduction in sensitivity of this magnitude would not be expected to have a large
      impact on the effectiveness of information transfer via the auditory modality.

PMID- 14692468
TI  - Sensorimotor performance and computational demand during short-term exposure to
      microgravity.
AB  - INTRODUCTION: Previous research suggests that human sensorimotor performance
      depends both on task difficulty, and on the allocation of the brain's
      computational resources to the task. We employ this view to analyze the changes
      of sensorimotor performance during the microgravity episodes of parabolic flight.
      METHODS: There were seven subjects who participated before, during, and after
      exposure to the microgravity episodes of parabolic flight. They performed a
      tracking task with one hand, and a four-choice reaction time task with the other
      hand, either alone or concurrently. Overall performance scores across tasks were
      calculated. RESULTS: Overall single-task performance deteriorated by about 50%
      microgravity, with little sign of recovery during the flight. Overall dual-task
      interference was more than twice as great at the onset of microgravity than at
      the onset of the 1-G baseline, but converged toward that baseline within about
      4.5 min. CONCLUSIONS: Our subjects accepted a consistently poor level of
      sensorimotor performance throughout exposure to microgravity. To maintain that
      level, they increased the allocation of computational resources to the tasks at
      the onset of microgravity, but an increase was no longer necessary after 4.5 min
      of microgravity exposure. We take the initial increase as evidence of a brief
      phase of sensorimotor adaptation.

PMID- 14692469
TI  - Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor
      performance.
AB  - INTRODUCTION: Modern military operations may require pharmaceutical methods to
      sustain alertness and facilitate sleep in order to maintain operational
      readiness. In operations with very limited sleep windows, hypnotics with very
      short half-lives (e.g., zaleplon, t(1/2) 1 h) are of interest, while with longer
      sleep opportunities, longer acting agents (e.g., zopiclone, temazepam (t(1/2) 4-6
      hours) may be used. This study was designed to compare the effect of a single
      dose of zaleplon, zopiclone, temazepam, and melatonin on psychomotor performance
      and to quantify the post-ingestion time required for return to normal
      performance. METHOD: There were 23 subjects (9 men, 14 women), 21-53 yr of age,
      assessed for psychomotor performance on 2 test batteries (4 tasks) that included
      a sleepiness questionnaire. Psychomotor testing was conducted prior to, and for 7
      h after, ingestion of a single dose of each of placebo, zaleplon 10 mg, zopiclone
      7.5 mg, temazepam 15 mg, and time-released melatonin 6 mg. The experimental
      design was a double-blind cross-over with counter-balanced treatment order.
      RESULTS: Zaleplon, zopiclone, and temazepam impaired performance on all four
      tasks: serial reaction time (SRT), logical reasoning (LRT), serial subtraction
      (SST), and multitask (MT). Melatonin did not impair performance on any task. The
      time to recovery of normal performance for SRT during the zaleplon, zopiclone and
      temazepam conditions were 3.25, 6.25, and 5.25 h respectively; for LRT were 3.25,
      >6.25, and 4.25 h; for SST were 2.25, >6.25, and 4.25 h, and for MT were 2.25,
      4.25, and 3.25 h. The recovery time to baseline subjective sleepiness levels for
      zaleplon, zopiclone, temazepam, and melatonin were 4.25, >6.25, 5.25, and >4.25
      h, respectively. CONCLUSIONS: In spite of a prolonged period of perceived
      sleepiness, melatonin was superior to zaleplon in causing no impact on
      performance. The remaining drugs listed in increasing order of performance impact
      duration are zaleplon, temazepam, and zopiclone.

PMID- 14692470
TI  - Cigarette smoking and decompression illness severity: a retrospective study in
      recreational divers.
AB  - BACKGROUND: Severe decompression illness (DCI) could be more likely in cigarette
      smokers because of airway obstruction or vascular disease. The present study
      evaluated the severity of DCI as a function of cigarette smoking in recreational
      divers. METHODS: We examined all DCI reports recorded in the Divers Alert Network
      (DAN) database from 1989 through 1997. Smoking history was quantified as heavy
      (>15 pack-years), light (0 to 15 pack-years), and never smoked. DCI symptoms were
      classified as severe (alteration in consciousness, balance or bladder/bowel
      control, motor weakness, visual symptoms, convulsions), moderate (other
      neurological symptoms), or mild (pain, skin, or nonspecific symptoms). The
      proportional odds model and generalized logits were used for the adjusted
      analysis when accounting for other covariates. RESULTS: There were 4,350 patients
      included in the analysis. After adjustment for confounding variables, heavy
      smokers were more likely to have severe vs. mild symptoms than nonsmokers (OR =
      1.88) (95% CI 1.36, 2.60) or light smokers (OR = 1.56) (95% CI 1.09, 2.23). Heavy
      smokers and light smokers were more likely to have severe vs. moderate symptoms
      than nonsmokers (OR = 1.36) (95% CI 1.06, 1.74) and (1.22) (1.02, 1.46),
      respectively. Although these data do not reveal whether smoking predisposes to
      DCI, the results are consistent with a tendency, when DCI occurs, for cigarette
      smoking to trigger more severe symptoms. CONCLUSIONS: The data suggest that when
      DCI occurs in recreational divers, smoking is a risk factor for increased
      severity of symptoms.

PMID- 14692471
TI  - Should divers smoke and vice versa?

PMID- 14692472
TI  - Venous thromboembolism in passengers following a 12-h flight: a case-control
      study.
AB  - OBJECTIVES: There has recently been great interest in the possible relationship
      between air travel and venous thromboembolism (VTE). Based on a case-control
      survey, we measured the frequency of VTE, associated risk factors (RFs), and
      factors influencing the onset of pulmonary embolism (PE) or deep vein thrombosis
      (DVT). METHODS: The study was conducted over 1 yr. A questionnaire was sent to
      physicians. Patients with a diagnosis of VTE were included, provided they had
      traveled from France to Reunion Island. RESULTS: Over 46 cases, 33 patients
      showed DVT and 13 PE. RFs for VTE were present in 38 patients (82%). On comparing
      RFs between study and control groups, we found no differences in age, gender,
      alcohol, sleep-inducing drug consumption, seat allocation, or estroprogestative
      treatment. RFs were significantly higher in the VTE group at p < 0.005: history
      of previous VTE (OR 63.3), recent trauma (OR 13.6), presence of varicose veins
      (OR 10), obesity (OR 9.6), immobility during flight (9.3), and cardiac disease
      (OR 8.9). For patients with DVT or PE, no differences were observed in comparing
      RFs. The PE group was older and mortality occurred only in this group. The number
      of displacements during flight (p < 0.009) and complete immobility (p < 0.001)
      were strongly related with onset of PE. Delay of symptoms was less than 24 h in
      69% of PE cases compared with 21% of DVT cases (p < 0.004). CONCLUSION: Long
      duration air travel VTE is associated with other underlying thromboembolic RFs.
      Low mobility during flight is a striking modifiable RF of developing PE.
      Travelers with RFs for VTE should be advised to increase their mobility.

PMID- 14692473
TI  - Effects of mission duration on neuroimmune responses in astronauts.
AB  - BACKGROUND: Spaceflight poses a unique stress to humans that can impair cellular
      immune responses and reactivate latent herpes viruses. Notably, prior studies
      have suggested that mission length may be an important factor in the variability
      of immune alterations observed after spaceflight. In this study, adrenocortical
      responses and circulating leukocytes were compared between astronauts who
      participated in either 9- or 16-d missions. HYPOTHESIS: Mission duration will
      differentially affect neuroimmune responses after spaceflight. METHODS: Blood and
      urine samples, collected from 28 crew-members who flew on 5 Space Shuttle
      missions, were analyzed for levels of plasma and urinary cortisol, urinary
      catecholamines, leukocyte and lymphocyte subsets, and total IgE. RESULTS: After
      spaceflight, plasma cortisol was significantly decreased after the 9-d missions
      but increased after the 16-d missions. In contrast urinary epinephrine and
      norepinephrine levels were greater after the 9-d missions than the 16-d missions.
      Total IgE was significantly increased after the 16-d missions and correlated with
      urinary cortisol. The number of white blood cells, polymorphonuclear leukocytes,
      and CD4+ T cells were significantly increased postflight. After the 9-d missions,
      monocytes were increased while natural killer cells were decreased. However,
      monocytes were decreased after the 16-d missions; no change occurred in natural
      killer cells. CONCLUSIONS: These results suggest that sympathetic nervous system
      responses predominate after shorter spaceflights, while longer flights are
      characterized by glucocorticoid-mediated changes at landing that may result from
      the accumulative effects of microgravity (i.e., physiological deconditioning)
      over time.

PMID- 14692474
TI  - Occupational exposure to hydrazines: treatment of acute central nervous system
      toxicity.
AB  - Exposure to hydrazine and hydrazines' alkylated derivatives is an important
      occupational health issue, which will increase in significance as space
      applications increase. Despite their widespread usage as rocket fuels in manned
      and unmanned space and missile systems, serious exposures to hydrazines are rare.
      While a significant number of experimental studies were performed in the late
      1950s through the mid-1960s, conflicting information exists concerning the most
      appropriate treatment for these exposures. A cross-sectional study evaluating the
      most common rocket fuels such as hydrazine; 1,1-dimethylhydrazine (UDMH); mono
      methylhydrazine (MMH); and Aerozine-50 against the most commonly suggested
      therapies, such as pyridoxine, traditional antiseizure therapies, and arginine is
      needed to clarify the treatment implications for human exposure. Treatments that
      have been useful for hyperammonemic states, such as those for the six inherited
      urea cycle defects, have significant potential for the improvement of hydrazine
      exposure treatment.

PMID- 14692475
TI  - Left bundle branch block and private pilot licensing.
AB  - Three otherwise healthy private pilots were licensed with the restriction to fly
      "as or with safety pilot" because of a left bundle branch block (LBBB). Whether a
      pilot with this conduction disturbance is allowed to fly unrestricted depends on
      invasive diagnostic procedures. Above age 40, cardiovascular risk in subjects
      with LBBB becomes high enough that a flying license should be withheld. A
      protocol for licensing in LBBB cases under age 40 is given, relying on non
      invasive diagnostic procedures, taking into account intermittent occurrence,
      electrical axis, and duration of QRS complex.

PMID- 14692476
TI  - Ethics in human experimentation: the two military physicians who helped develop
      the Nuremberg Code.
AB  - The Nuremberg Code is generally considered the beginning of modern ethics in
      human experimentation. The Code is a list of 10 principles that Judge Walter
      Beals included in the judgment he delivered at the close of the Nuremberg Medical
      Trial on 19 August 1947. Recently, scholars have studied the origin of the Code,
      who wrote it, and why. This is important to military medicine and the Aerospace
      Medical Association in particular because many of the defendants claimed their
      crimes were experiments in aviation and environmental physiology conducted under
      wartime conditions. The chief prosecutor of the Nuremberg Medical Trial, General
      Telford Taylor, relied on the guidance of an advisor provided by the American
      Medical Association, Andrew C. Ivy, one of the foremost physiologists of his
      time. The neurologist, Leo Alexander, then a colonel in the U.S. Army Reserves,
      was another medical advisor. Both men were crucial to the development of Taylor's
      courtroom strategy. The material Alexander and Ivy provided was incorporated
      verbatim in the section of the judgment that became the Code. Although both men
      contributed to the Code, Ivy provided what seems to be the first formulation of
      many of these principles during a meeting of Allied medical investigators at the
      Pasteur Institute in July 1946. Naval researchers should note that Ivy had been
      the Director of the Research Division of the Naval Medical Research Institute
      when it was commissioned on October 27, 1942.

PMID- 14692477
TI  - Titanium in a hyperbaric oxygen environment may pose a fire risk.
AB  - The use of titanium during hyperbaric oxygen therapy may pose a risk of fire. A
      fresh titanium surface in a high oxygen atmosphere can be a source of ignition.
      The clinical scenario may be a patient who accidentally breaks his titanium
      framed glasses during a hyperbaric oxygen treatment in a monoplace chamber or
      using an oxygen hood. We recommend some safety precautions to be exercised until
      consensus standards have been established by the hyperbaric medicine community.

PMID- 14692478
TI  - Cases from the aerospace medicine residents' teaching file. Transient ischemic
      attack in an aviator with patent foramen ovale and Factor V Leiden.
AB  - A case report is presented of a naval aviator who suffered a transient ischemic
      attack (TIA) 1 mo after experiencing right leg pain and swelling following a 4-d
      drive. Although a venous thrombotic source was never discovered, the presence of
      both a patent foramen ovale and a thrombophilic condition supports paradoxical
      embolism (PDE) as the cause of this pilot's TIA. The presentation, diagnosis,
      treatment, and aeromedical disposition of TIA secondary to a PDE is discussed.

PMID- 14692479
TI  - You're the flight surgeon. Plague.

PMID- 14692480
TI  - This month in aerospace medicine history--November 2003.

PMID- 14692481
TI  - This month in aerospace medicine history--December 2003.

PMID- 14692482
TI  - The history of the Aerospace Physiology Society--part I.

PMID- 14692483
TI  - Information-processing demands in electrosensory and mechanosensory lateral line
      systems.
AB  - The electrosensory and mechanosensory lateral line systems of fish exhibit many
      common features in their structural and functional organization, both at the
      sensory periphery as well as in central processing pathways. These two sensory
      systems also appear to play similar roles in many behavioral tasks such as prey
      capture, orientation with respect to external environmental cues, navigation in
      low-light conditions, and mediation of interactions with nearby animals. In this
      paper, we briefly review key morphological, physiological, and behavioral aspects
      of these two closely related sensory systems. We present arguments that the
      information processing demands associated with spatial processing are likely to
      be quite similar, due largely to the spatial organization of both systems and the
      predominantly dipolar nature of many electrosensory and mechanosensory stimulus
      fields. Demands associated with temporal processing may be quite different,
      however, due primarily to differences in the physical bases of electrosensory and
      mechanosensory stimuli (e.g. speed of transmission). With a better sense of the
      information processing requirements, we turn our attention to an analysis of the
      functional organization of the associated first-order sensory nuclei in the
      hindbrain, including the medial octavolateral nucleus (MON), dorsal octavolateral
      nucleus (DON), and electrosensory lateral line lobe (ELL). One common feature of
      these systems is a set of neural mechanisms for improving signal-to-noise ratios,
      including mechanisms for adaptive suppression of reafferent signals. This
      comparative analysis provides new insights into how the nervous system extracts
      biologically significant information from dipolar stimulus fields in order to
      solve a variety of behaviorally relevant problems faced by aquatic animals.

PMID- 14692484
TI  - The physical nature of life.
AB  - Life evolved from the primeval world of physics. Sensory systems inform animals
      of the natural environment, enabling them to conduct responsively. The discovery
      of weak, DC bioelectric fields in the vicinity of aquatic organisms and the role
      they play in guiding sharks and rays to their prey have led to the recognition of
      fundamental, hitherto less well known, physical aspects of sensory biology. The
      inferred cybernetic algorithm of electric-field orientation in sharks and rays is
      highly effective and extremely robust. In orienting to the weak DC electric
      fields of ocean currents and to the earth's magnetic field, sharks and rays
      unwittingly practise the motional-electric principles that Einstein had in mind
      when he introduced the special theory of relativity. At the sense-organ, receptor
      membrane, and ion-channel levels, the elasmobranch ampullae of Lorenzini operate
      on the basis of graded positive feedback driven by negative conductance,
      supposedly employing voltage-sensitive ion channels as the active, excitable
      elements. The electric sense of sharks and rays presents an exquisite
      implementation of the very biophysical principles that also govern the graded,
      much richer than all-or-none, integrative brain processes of animal and man.

PMID- 14692485
TI  - The electric sense of the paddlefish: a passive system for the detection and
      capture of zooplankton prey.
AB  - Behavioral and electrophysiological experiments have shown that the elongated
      paddlefish rostrum, with its extensive population of ampullae of Lorenzini,
      constitutes a passive electrosensory antenna of great sensitivity and spatial
      resolution. As demonstrated in juvenile paddlefish, the passive electrosense
      serves a novel function in feeding serving as the primary, if not exclusive
      sensory modality for the detection and capture of zooplanktonic prey. Ampullary
      receptors are sensitive to the weak electrical fields of plankton from distances
      up to 9 cm, and juvenile paddlefish capture plankton individually with great
      swimming dexterity in the absence of vision or other stimulus signals. Paddlefish
      also detect and avoid metal obstacles, the electrical signatures of which are a
      potential hindrance to their feeding and reproductive migrations. The ampullary
      receptors, their peripheral innervation and central targets in the dorsal
      octavolateral nucleus, are described. We also describe the ascending and
      descending neuronal circuitry of the electrosensory system in the brain based on
      tracer studies using dextran amines.

PMID- 14692486
TI  - Neuroethology and life history adaptations of the elasmobranch electric sense.
AB  - The electric sense of elasmobranch fishes (sharks and rays) is an important
      sensory modality known to mediate the detection of bioelectric stimuli. Although
      the best known function for the use of the elasmobranch electric sense is prey
      detection, relatively few studies have investigated other possible biological
      functions. Here, we review recent studies that demonstrate the elasmobranch
      electrosensory system functions in a wide number of behavioral contexts including
      social, reproductive and anti-predator behaviors. Recent work on non-electrogenic
      stingrays demonstrates that the electric sense is used during reproduction and
      courtship for conspecific detection and localization. Electrogenic skates may use
      their electrosensory encoding capabilities and electric organ discharges for
      communication during social and reproductive interactions. The electric sense may
      also be used to detect and avoid predators during early life history stages in
      many elasmobranch species. Embryonic clearnose skates demonstrate a ventilatory
      freeze response when a weak low-frequency electric field is imposed upon the egg
      capsule. Peak frequency sensitivity of the peripheral electrosensory system in
      embryonic skates matches the low frequencies of phasic electric stimuli produced
      by natural fish egg-predators. Neurophysiology experiments reveal that
      electrosensory tuning changes across the life history of a species and also
      seasonally due to steroid hormone changes during the reproductive season. We
      argue that the ontogenetic and seasonal variation in electrosensory tuning
      represent an adaptive electrosensory plasticity that may be common to many
      elasmobranchs to enhance an individual's fitness throughout its life history.

PMID- 14692487
TI  - Ampullary organs and electroreception in freshwater Carcharhinus leucas.
AB  - The ampulla of Lorenzini of juvenile Carcharhlinus leucas differ histologically
      from those previously described for other elasmobranchs. The wall of the
      ampullary canal consists of protruding hillock-shaped epidermal cells that appear
      to secrete large quantities of a mucopolysaccharide gel. The ampullary organs
      comprise a long canal sheathed in collagen terminating in an ampulla. Each
      ampulla contains six alveolar sacs, with each sac containing hundreds of receptor
      cells. The receptor cells are characteristic of others described for
      elasmobranchs being pear-shaped cells with a central nucleus and bearing a single
      kinocilium in the exposed apical region of the cell. The supportive cells differ
      from general elasmobranch ampullary histology in that some have an apical
      nucleus. These ampullary structures allow Carcharhinus leucas to detect and
      respond to artificial electrical fields. Carcharhinus leucas from freshwater
      habitats respond to electrical signals supplied in freshwater aquaria by abruptly
      turning towards low voltage stimuli (< or = 10 microA) and either swimming over
      or biting at the origin of the stimulus.

PMID- 14692488
TI  - The bioelectric field of the catfish Ictalurus nebulosus.
AB  - The variability of the bioelectric field of the electrosensitive catfish,
      Ictalurus nebulosus, was investigated by recording the potential variation
      occurring when the fish passed a stationary electrode, and by recording the field
      of a stationary fish by a 15-electrode array. A good first order approximation of
      the recorded field of a 20 cm long fish is a dipole dc source with the source and
      sink about 7 cm apart, carrying a current of about 1 microA in water with a
      specific resistivity of 3.3 kohm cm. At 5 cm distance from the dipole axis such a
      source generates an electric potential swing in the order of 50 microV in free
      space, head negative, tail positive. Superimposed on the basic component are
      respiration related fluctuations, and fluctuations related to the activity of the
      alimentary canal, gills, and skin. Novel stimuli, or stressors like investigators
      approaching the aquarium, evoke sudden increases in field strength. which last
      about 15 min. Demineralization of the aquarium water causes changes in field
      strength and reversal of field polarity. The administration of food causes field
      variations in the vicinity of the anal opening. The bioelectric field shows
      diurnal fluctuations of 100 microV. The peak is at about 04:00, the dip at 14:00.
      The fluctuations of the bioelectric field are sufficiently strong and specilic to
      serve as electrical stimuli to other electrosensitive catfish. It is suggested
      that the field changes allow a simple form of electrocommunication. i.e. inform
      conspecifics about some physiological properties of the field source. The
      cellular mechanisms underlying the fluctuations of the bioelectric field are
      homeostatic processes mediated by ion pumps and ion channels.

PMID- 14692489
TI  - Electric signaling behavior and the mechanisms of electric organ discharge
      production in mormyrid fish.
AB  - Mormyrid fish communicate and navigate using electric organ discharges (EODs).
      The EOD is highly stereotyped and provides information on sender identity,
      including species, sex, reproductive condition, and possibly relative status and
      individual identity. By contrast, the sequence of pulse intervals (SPI) is
      variable and plays more of a role in signaling behavioral states. Various types
      of SPI displays may be produced, including tonic patterns such as 'random' and
      'regularized', and phasic patterns such as 'bursts' and cessations'. Certain
      displays have been linked to specific behaviors such as aggression, submission,
      courtship and active exploration. In addition, interacting pairs of fish may
      produce stereotyped displays involving the relative timing of their EODs. The EOD
      waveform is controlled by the morphological and physiological properties of cells
      in the electric organ termed electrocytes. Differences in the innervation,
      morphology, size and membrane characteristics of electrocytes have been directly
      linked to species and sex differences in the EOD. The generation of each EOD is
      initiated in the medullary command nucleus (CN), which thereby determines the
      timing of EOD output. CN does not have any properties of a pacemaker, but rather
      appears to integrate descending inputs that affect the probability of EOD
      production. The precommand nucleus (PCN) provides a major source of excitatory
      input to CN and is itself inhibited by corollary discharge feedback following the
      production of each EOD. Changes in the activity of PCN and its inhibitory
      feedback neurons modify EOD output, and therefore drive the generation of SPI
      patterns. Current studies are addressing the mechanisms underlying the generation
      of these patterns and preliminary results suggest that different types of signals
      may be controlled by distinct components of the electromotor system. This is
      similar to findings in other electrogenic teleosts, suggesting that it may be a
      general feature in the motor control of signaling behavior.

PMID- 14692490
TI  - The electric image in Gnathonemus petersii.
AB  - We review modelling and experimental work dealing with the mechanisms of
      generation of electric image. We discuss: (1) the concept of electric image in
      the context of the reafference principle; (2) how waveform codes an impedance
      related qualia of the object image, referred to as "electric colour"; (3) that
      some characteristics of the spatial profiles generated by pre-receptor mechanisms
      are suitable for edge detection; (4) which parameters of the spatial profiles
      provide information for distance discrimination; (5) that electric images are
      distributed representations of the scene.

PMID- 14692491
TI  - Imaging of objects through active electrolocation in Gnathonemus petersii.
AB  - The weakly electric fish Gnathonemus petersii detects, localizes, and analyzes
      objects during active electrolocation even in complete darkness. This enables
      these fish to lead a nocturnal life and find and identify their prey (small
      insect larvae) on the ground of their freshwater habitat. During active
      electrolocation, fish produce a series of brief electric signals, electric organ
      discharges (EOD), with an electric organ in their tail. Each EOD builds up a
      stable electric field around the fish, which is distorted only by nearby objects.
      Field distortions lead to changes of the transepidermal electric current flow at
      a region of the fish's electroreceptive skin surface called the 'electric image'.
      Within the electric image, locally perceived EODs can be either altered in
      amplitude or waveform by an object. Fish measure both parameters to assess object
      properties, such as the capacitive and resistive components of the object's
      complex impedance. the object's size and shape, and its distance from the fish.
      None of these object properties can be evaluated in isolation, but have to be
      inferred during parallel processing of electric image spatial and qualitative
      parameters. Two anterior skin regions of G. petersii appear to possess particular
      properties for special electrolocation tasks and we therefore refer to them as
      'foveal' regions. Because of its high electroreceptor density, the electric field
      geometry around it, and its behavioral use, the 'nasal region' between the nares
      and the mouth at the head of the fish is suggested to be a fovea for long-range
      guidance and object detection. We propose that the 'Schnauzenorgan', a long and
      flexible chin appendix covered densely with electroreceptor organs, is a second
      electroreceptive fovea associated with a short-range (food) identification
      system. Together, these two electric foveae constitute an effective prey
      detection and identification system.

PMID- 14692492
TI  - Active control of spike-timing dependent synaptic plasticity in an electrosensory
      system.
AB  - A spike timing dependent learning rule is present at the synapse between parallel
      fibers and Purkinje-like medium ganglion cells in the electrosensory lobe of
      mormyrid electric fish. The synapse is depressed when a postsynaptic dendritic
      spike occurs within 50 ms of the onset of a parallel fiber excitatory
      postsynaptic potential, but is enhanced at all other timing relations. Operation
      of this learning rule results in the cancellation of predictable membrane
      potential changes, driving the cell towards a constant output frequency. But
      medium ganglion cells show a strong and predictable response to corollary
      discharge signals associated with the motor command that initiates the electric
      organ discharge. The modeling study presented here resolves this conflict by
      proposing an active control of dendritic spike threshold during the brief period
      of medium ganglion cell response.

PMID- 14692493
TI  - EOD modulations of brown ghost electric fish: JARs, chirps, rises, and dips.
AB  - Weakly electric "wave" fish make highly regular electric organ discharges (EODs)
      for precise electrolocation. Yet, they modulate the ongoing rhythmicity of their
      EOD during social interactions. These modulations may last from a few
      milliseconds to tens of minutes. In this paper we describe the different types of
      EOD modulations, what they may signal to recipient fish, and how they are
      generated on a neural level. Our main conclusions, based on a species called the
      brown ghost (Apteronotus leptorhynchus) are that fish: (1) show sexual dimorphism
      in the signals that they generate; (2) make different signals depending on
      Whether they are interacting with a fish of the opposite sex or, within their own
      sex, to a fish of that which is dominant or subordinate to it; (3) are able to
      assess relative dominance from electrical cues; (4) have a type of plasticity in
      the pacemaker nucleus, the control center for the EOD, that occurs after
      stimulation of NMDA receptors that causes a long-lasting (tens of minutes to
      hours) change in EOD frequency; (5) that this NMDA receptor-dependent change may
      occur in reflexive responses, like the jamming avoidance response (JAR), as well
      as after certain long-lasting social signals. We propose that NMDA-receptor
      dependent increases in EOD frequency during the JAR adaptively shift the EOD
      frequency to a new value to avoid jamming by another fish and that such increases
      in EOD frequency during social encounters may be advantageous since social
      dominance seems to be positively correlated with EOD frequency in both sexes.

PMID- 14692494
TI  - From oscillators to modulators: behavioral and neural control of modulations of
      the electric organ discharge in the gymnotiform fish, Apteronotus leptorhynchus.
AB  - The brown ghost (Apteronotus leptorhynchus) is a weakly electric gymnotiform fish
      that produces wave-like electric organ discharges distinguished by their enormous
      degree of regularity. Transient modulations of these discharges occur both
      spontaneously and when stimulating the fish with external electric signals that
      mimic encounters with a neighboring fish. Two prominent forms of modulations are
      chirps and gradual frequency rises. Chirps are complex frequency and amplitude
      modulations lasting between 20 ms and more than 200 ms. Based on their
      biophysical characteristics, they can be divided into four distinct categories.
      Gradual frequency rises consist of a rise in discharge frequency, followed by a
      slow return to baseline frequency. Although the modulatory phase may vary
      considerably between a few 100 ms and almost 100 s, there is no evidence for the
      existence of distinct categories of this type of modulation signal. Stimulation
      of the fish with external electric signals results almost exclusively in the
      generation of type-2 chirps. This effect is independent of the chirp type
      generated by the respective individual under non-evoked conditions. By contrast,
      no proper stimulation condition is known to evoke the other three types of chirps
      or gradual frequency rises in non-breeding fish. In contrast to the type-2 chirps
      evoked when subjecting the fish to external electric stimulation, the rate of
      spontaneously produced chirps is quite low. However, their rate appears to be
      optimized according to the probability of encountering a conspecific. As a
      result, the rate of non-evoked chirping is increased during the night when the
      fish exhibit high locomotor activity and in the time period following external
      electric stimulation. These, as well as other, observations demonstrate that both
      the type and rate of modulatory behavior are affected by a variety of behavioral
      conditions. This diversity at the behavioral level correlates with, and is likely
      to be causally linked to, the diversity of inputs received by the neurons that
      control chirps and gradual frequency rises, respectively. These neurons form two
      distinct sub-nuclei within the central posterior/prepacemaker nucleus in the
      dorsal thalamus. In vitro tract-tracing experiments have elucidated some of the
      connections of this complex with other brain regions. Direct input is received
      from the optic tectum. Indirect input arising from telencephalic and hypothalamic
      regions, as well as from the preoptic area, is relayed to the central
      posterior/prepacemaker nucleus via the preglomerular nucleus. Feedback loops may
      be provided by projections of the central posterior/prepacemaker nucleus to the
      preglomerular nucleus and the nucleus preopticus periventricularis.

PMID- 14692495
TI  - Environmental and hormonal influences upon EOD waveform in gymnotiform pulse
      fish.
AB  - Temperature is a major variable that affects all biological systems.
      Environmental temperature determines animal geographical distribution and
      activity, and influences their reproductive cycle, particularly within the
      temperate zone. Temperature, as a physical parameter, also strongly affects
      excitable tissues. The hypothesis of temperature as the most important
      environmental cue for the onset of breeding in gymnotiform pulse fish of the
      temperate zone is supported by: (a) a clear temporal correlation that was
      observed in the wild between water temperature and sexual maturity, and (b) the
      induction of gonadal maturation and sexual differences after acclimation at high
      temperature (28 degrees C) in the laboratory. Temperature sensitivity of EOD
      waveform (described in Brachyhypopomus pinnicaudatus and Gymnotus carapo) is
      characterized by the decrease of the EOD's late head-negative phase as
      temperature increases. This phenomenon depends on electrocyte properties since:
      (a) experimentally induced changes of discharge rate at constant temperature
      generate smaller EOD distortion, and (b) the effect of temperature upon EOD also
      depends on water conductivity. Temperature sensitivity of EOD waveform is
      negatively correlated with gonadal maturity in Brachyhypopomus pinnicaudatus.
      High temperature sensitivity was observed during the non-breeding season, whereas
      low temperature sensitivity was recorded during the breeding season. Temperature
      sensitivity of EOD waveform in both Brachyhypopomus pinnicaudatus and Gymnotus
      carapo was modulated by: (a) testosterone treatment (100 microg/g) that decreased
      temperature sensitivity, and (b) acclimation at high temperature (28 degrees C, 1
      month) that also decreased temperature sensitivity. Temperature is probably
      acting through the neuroendocrine system, and ultimately interacting with steroid
      hormones in their effects upon EOD waveform.

PMID- 14692496
TI  - The evolutionary origins of electric signal complexity.
AB  - This study explores the evolutionary origins of waveform complexity in electric
      organ discharges (EODs) of weakly electric fish. I attempt to answer the basic
      question of what selective forces led to the transition from the simplest signal
      to the second simplest signal in the gymnotiform electric fishes. The simplest
      electric signal is a monophasic pulse and the second simplest is a biphasic
      pulse. I consider five adaptive hypotheses for the evolutionary transition from a
      monophasic to a biphasic EOD: (i) electrolocation, (ii) sexual selection, (iii)
      species isolation, (iv) territory defense, (v) crypsis from electroreceptive
      predators. Evaluating these hypotheses with data drawn largely from the
      literature, I find best support for predation. Predation is typically viewed as a
      restraining force on evolution of communication signals, but among the electric
      fishes, predation appears to have served as a creative catalyst. In suppressing
      spectral energy in the sensitivity range of predators (a spectral
      simplification), the EOD waveforms have become more complex in their time domain
      structure. Complexity in the time domain is readily discernable by the high
      frequency electroreceptor systems of gymnotiform and mormyrid electric fish. The
      addition of phases to the EOD can cloak the EOD from predators, but also provides
      a substrate for subsequent modification by sexual selection. But, while juveniles
      and females remain protected from predators, breeding males modify their EODs in
      ways that enhance their conspicuousness to predators.

PMID- 14692497
TI  - Electrolocation and electrocommunication in pulse gymnotids: signal carriers, pre
      receptor mechanisms and the electrosensory mosaic.
AB  - Constraints introduced by signal carriers, pre-receptor mechanisms and receptor
      transduction are fundamental for shaping the signals used by the brain to build
      up perceptual images. This review analyses some of these constraints in the
      electrosensory system of pulse Gymnotids. First, it describes the characteristics
      and differences of electrolocation and electrocommunication carriers. Second, it
      analyses the role of electrogenic and non-electrogenic tissues of the fish body
      in the generation and conditioning of these carriers. Two pre-receptor mechanisms
      are discussed: (a) the funneling of currents to the perioral region and (b) a
      Mexican-hat profile involved in edge detection. Finally, some characteristics of
      the electroreceptor structure and the sensory mosaic are examined. We conclude
      that there is an electrosensory fovea at the perioral region where a large
      density and variety of receptors is stimulated by self- and conspecific-generated
      currents funneled there by non electrogenic tissues. Differences in carrier
      waveform may be used to distinguish between reafferent and communication signals.

PMID- 14692498
TI  - Multiscale spike train variability in primary electrosensory afferents.
AB  - Spike train variability is of fundamental importance for understanding how
      information is encoded and processed in the nervous system. Most studies in this
      area have focused on short-term variability, as characterized by the coefficient
      of variation of the interspike interval distribution. Here we discuss the
      importance of extending the analysis of spike train variability to longer time
      scales that span multiple interspike intervals. Recent experimental and modeling
      studies of probability coding (P-type) electrosensory afferent nerve fibers in
      weakly electric fish have provided new insights into the functional importance of
      multiscale spike train variability. P-type afferent spike trains are moderately
      irregular on short time scales of a few milliseconds, but show significantly
      enhanced regularity on time scales of a few hundred milliseconds. This increased
      regularity is beyond what would be expected for a renewal process model in which
      successive intervals are uncorrelated. Modeling studies suggest that the
      correlation structure that underlies spike train regularization arises from
      relative refractory effects associated with a dynamic spike threshold. Spike
      train regularization in P-type afferents has been shown to significantly enhance
      signal detectability and information transmission on time scales that are
      functionally relevant for electrolocation behavior.

PMID- 14692499
TI  - Oscillatory burst discharge generated through conditional backpropagation of
      dendritic spikes.
AB  - Gamma frequencies of burst discharge (>40 Hz) have become recognized in select
      cortical and non-cortical regions as being important in feature extraction,
      neural synchrony and oscillatory discharge. Pyramidal cells of the electrosensory
      lateral line lobe (ELL) of Apteronotus leptorhynchus generate burst discharge in
      relation to specific features of sensory input in vivo that resemble those
      recognized as gamma frequency discharge when examined in vitro. We have shown
      that these bursts are generated by an entirely novel mechanism termed conditional
      backpropagation that involves an intermittent failure of dendritic Na+ spike
      conduction. Conditional backpropagation arises from a frequency-dependent
      broadening of dendritic spikes during repetitive discharge, and a mismatch
      between the refractory periods of somatic and dendritic spikes. A high threshold
      class of K+ channel, AptKv3.3, is expressed at high levels and distributed over
      the entire soma-dendritic axis of pyramidal cells. AptKv3.3 channels are shown to
      contribute to the repolarization of both somatic and dendritic spikes, with
      pharmacological blockade of dendritic Kv3 channels revealing an important role in
      controlling the threshold for burst discharge. The entire process of conditional
      back-propagation and burst output is successfully simulated using a new
      compartmental model of pyramidal cells that incorporates a cumulative
      inactivation of dendritic K+ channels during repetitive discharge. This work is
      important in demonstrating how the success of spike backpropagation can control
      the output of a principle sensory neuron, and how this process is regulated by
      the distribution and properties of voltage-dependent K+ channels.

PMID- 14692500
TI  - Emergence of temporal-pattern sensitive neurons in the midbrain of weakly
      electric fish Gymnarchus niloticus.
AB  - Sensitivity of neurons in the torus semicircularis of a weakly electric fish,
      Gymnarchus niloticus, to two stimulus parameters that are critical for its
      behavior the jamming avoidance response was examined. The first parameter is the
      sign of frequency difference between discharge frequencies of fish's own electric
      organ and that of a neighbor's. The second parameter is the spatial orientation
      of neighbor's electric field. Whereas neuronal ambiguity of frequency coding for
      different orientations of neighbor's electric field is predicted, unambiguous JAR
      occurs at the behavioral level. Most neurons in the torus semicircularis showed
      sensitivity to the sign of frequency difference. Although a small number of
      neurons showed preference to a consistent sign of the frequency difference, the
      coding of the sign of frequency differences was found to be ambiguous with a
      highly variable pattern of responses for different orientations in most of
      neurons.

PMID- 14692501
TI  - Roles for short-term synaptic plasticity in behavior.
AB  - Short-term synaptic plasticity is phylogenetically widespread in ascending
      sensory systems of vertebrate brains. Such plasticity is found at all levels of
      sensory processing, including in sensory cortices. The functional roles of this
      apparently ubiquitous short-term synaptic plasticity, however, are not well
      understood. Data obtained in midbrain electrosensory neurons of Eigenmannia
      suggest that this plasticity has at least two roles in sensory processing;
      enhancing low-pass temporal filtering and generating phase shifts used in
      processing moving sensory images. Short-term synaptic plasticity may serve
      similar roles in other sensory modalities, including vision.

PMID- 14692502
TI  - Multimodal sensory integration in weakly electric fish: a behavioral account.
AB  - The ability to integrate multisensory information is a fundamental characteristic
      of the brain serving to enhance the detection and identification of external
      stimuli. Weakly electric fish employ multiple senses in their interactions with
      one another and with their inanimate environment (electric, visual, acoustic,
      mechanical, chemical, thermal, and hydrostatic pressure) and also generate
      signals using some of the same stimulus energies (electric, acoustic, visual,
      mechanical). A brief overview provides background on the sensory and motor
      channels available to the fish followed by an examination of how weakly electric
      fish 'benefit' from integrating various stimulus modalities that assist in prey
      detection, schooling, foraging, courtship, and object location. Depending on
      environmental conditions, multiple sensory inputs can act synergistically and
      improve the task at hand, can be redundant or contradictory, and can substitute
      for one another. Over time, in repeated encounters with familiar surrounds, loss
      of one modality can be compensated for through learning. Studies of neuronal
      substrates and an understanding of the computational algorithms that underlie
      multisensory integration ought to expose the physiological corollaries to widely
      published concepts such as internal representation, sensory expectation, sensory
      generalization, and sensory transfer.

PMID- 14692503
TI  - Reproductive strategies and developmental aspects in mormyrid and gymnotiform
      fishes.
AB  - Comparative data on the reproduction in captivity and ontogenetic development of
      six of mormyrid species and seven gymnotiform species are reported. Mormyrid
      fishes: egg diameter ranged from 1.8 (Petroephalus soudanensis) to 3.0 mm
      (Hippopotamyrus pictus. Campylomormyrus phantasticus); fecundity (egg number per
      spawning) from 28 to 215 (Pollimyrus isidori) and 121 to 1662 (Campylomormyrus
      cassaicus); spawning intervals from 5 to 20 days (Pollimyrus isidori) and 15 to
      80 days (Campylomormyrus cassaicus). Pollimyrus isidori is the only species
      exhibiting parental care (in the male sex). Gymnotiform species: egg diameter
      ranged from 1.7 (Brachyhypopomus pinnicaudatus) to 3.0 mm (Sternopygus macrurus,
      Rhamphichthys sp., Gymnotus carapo); fecundity (egg number per spawning) from 1
      to 105 (Apteronotus leptorhynchus) and from approximately 500 to approximately
      1000 (Rhamphichthys sp.); spawning intervals from 2 to 5 days (Eigenmannia
      lineata) and from 20 to 41 days (Rhamphichthys sp.). Sternopyguls macrurus
      exhibited parental care (in the male sex) by guarding the eggs, whereas Gymnotus
      carapo revealed to be a mouthbreeder (guarding free embryos) in the male sex.
      Gonad maturation could be provoked by increase of conductivity alone in all
      mormyrid species tested and in several gymnotiform species. Four different stages
      of morphological development (hatchlings, larvae at beginning of exogenous
      feeding, juveniles, adults) are described in both taxa. The reproductive
      strategies of the gymnotiforms are considered more diverse than those of the
      mormyrids.

PMID- 14692504
TI  - The mechanism of L-canavanine cytotoxicity: arginyl tRNA synthetase as a novel
      target for anticancer drug discovery.
AB  - There is a clear need for agents with novel mechanisms of action to provide new
      therapeutic approaches for the treatment of pancreatic cancer. Owing to its
      structural similarity to L-arginine, L-canavanine, the beta-oxa-analog of L
      arginine, is a substrate for arginyl tRNA synthetase and is incorporated into
      nascent proteins in place of L-arginine. Although L-arginine and L-canavanine are
      structurally similar, the oxyguanidino group of L-canavanine is significantly
      less basic than the guanidino group of L-arginine. Consequently, L-canavanyl
      proteins lack the capacity to form crucial ionic interactions, resulting in
      altered protein structure and function, which leads to cellular death. Since L
      canavanine is selectively sequestered by the pancreas, it may be especially
      useful as an adjuvant therapy in the treatment of pancreatic cancer. This novel
      mechanism of cytotoxicity forms the basis for the anticancer activity of L
      canavanine and thus, arginyl tRNA synthetase may represent a novel target for the
      development of such therapeutic agents.

PMID- 14692505
TI  - Quantitative structure-activity relationship study of 5-iodo- and diaryl
      analogues of tubercidin: inhibitors of adenosine kinase.
AB  - The adenosine kinase inhibitory (AKI) activity of 5-iodo and diaryl analogues of
      tubercidin is quantitatively analyzed using Fujita-Ban and Hansch type analyses.
      The Fujita-Ban analysis being a non-parametric approach assigned the highest
      contribution to Cl at the X-position, C6H4-4-Cl, C6H5, 2-furanyl and I at the Y
      position and CH2NH2 and CH3 at the Z-position. In addition, a OH substituent at
      the C-position also emerged as a better choice possibly due to its engagement in
      hydrogen bonding with some active site function. Thus a compound having Cl, C6H4
      4-Cl, CH2NH2 and OH respectively at X-, Y-, Z- and C-positions is predicted to
      have a potency nearly 1.5 orders of magnitude higher than the most potent
      compound of the parent data set. The Hansch type analysis, on the other hand, is
      a parametric approach and is carried out on two sub-sets of original compounds.
      This sub-division is based on size and nature of the substituents present at the
      X- and Y-positions. For the compounds in the first sub-set the derived
      significant correlation equation suggested that the substituent at the Y-position
      exhibiting a higher field effect and a substituent such as Cl and CH2NH2 at X-
      and Z-positions, respectively, are important for a compound to show increased AKI
      activity. Thio/alkylthio at X and CH2OCH3 at Z, on the other hand, lead to a
      detrimental effect. Similarly for the compounds in the second subset, the derived
      significant correlation equation showed that a substituent at the X-position
      having a higher negative field effect, a substituent at the Y-position having
      bulky groups and the C-position occupied by a OH group are essential for
      enhancement of the activity of a compound.

PMID- 14692506
TI  - Carbonic anhydrase inhibitors. inhibition of cytosolic isozymes I and II and
      transmembrane, cancer-associated isozyme IX with anions.
AB  - Except for sulfonamides, metal complexing anions represent the second class of
      inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The first
      inhibition study of the transmembrane, tumor-associated isozyme CA IX with anions
      is reported here. Inhibition data of the cytosolic isozymes CA I and CA II with a
      large number of anionic species such as halides, pseudohalides, bicarbonate,
      nitrate, hydrosulfide, arsenate, etc., are also provided for comparison. Isozyme
      IX has an inhibition profile by anions different in some aspects from those of CA
      I and CA II, that may have interesting physiological consequences.

PMID- 14692507
TI  - Characterization of new milk-derived inhibitors of angiotensin converting enzyme
      in vitro and in vivo.
AB  - Inhibition of angiotensin converting enzyme (ACE) has been observed with a
      variety of different peptides, and peptide fragments with inhibitory capabilities
      have been identified within many different proteins, including milk proteins. The
      purpose of this study therefore was to identify new short peptides with
      inhibitory properties from the primary structure of milk proteins and to
      characterize them in vitro and in vivo, since no milk derived ACE inhibitors have
      previously been evaluated for their ability to inhibit ACE in vivo. In vitro, 8
      of 9 dipeptides were found to be competitive inhibitors of ACE. The IC50 was
      significantly lower when an angiotensin I-like substrate was used, than when a
      bradykinin-like substrate was used. Using three different in vivo models for ACE
      inhibition, a very moderate effect was observed for three of the new peptides,
      but only for up to 6 or 12 minutes. Nothing was observed with two reference
      compounds that are reported to be hypotensive ACE-inhibitors derived from milk
      proteins. This raises the question whether the mechanism of hypotensive action is
      straightforward inhibition of ACE in vivo.

PMID- 14692508
TI  - Irreversible inhibition of jack bean urease by pyrocatechol.
AB  - Pyrocatechol was studied as an inhibitor of jack bean urease in 20 mM phosphate
      buffer, pH 7.0, 25 degrees C. The inhibition was monitored by an incubation
      procedure in the absence of substrate and reaction progress studies in the
      presence of substrate. It was found that pyrocatechol acted as a time- and
      concentration dependent irreversible inactivator of urease. The dependence of the
      residual activity of urease on the incubation time showed that the rate of
      inhibition increased with time until there was total loss of enzyme activity. The
      inactivation process followed a non-pseudo-first order reaction. The obtained
      reaction progress curves were found to be time-dependent. The plots showed that
      the rate of the enzyme reaction in the final stages reached zero. From protection
      experiments it appeared that thiol-compounds such as L-cysteine, 2
      mercaptoethanol and dithiothreitol prevented urease from pyrocatechol
      inactivation as well as the substrate, urea, and the competitive inhibitor boric
      acid. These results proved that the urease active site was involved in the
      pyrocatechol inactivation.

PMID- 14692509
TI  - Inactivation of jack bean urease by allicin.
AB  - Allicin--diallyl thiosulfinate--is the main biologically active component of
      freshly crushed garlic. Allicin was synthesized as described elsewhere and was
      tested for its inhibitory ability against jack bean urease in 20 mM phosphate
      buffer, pH 7.0 at 22 degrees C. The results indicate that allicin is an enzymatic
      inactivator. The loss of urease activity was irreversible, time- and
      concentration dependent and the kinetics of the inactivation was biphasic; each
      phase, obeyed pseudo-first-order kinetics. The rate constants for inactivation
      were measured for the fast and slow phases and for several concentrations of
      allicin. Thiol reagents, and competitive inhibitor (boric acid) protected the
      enzyme from loss of enzymatic activity. The studies demonstrate that urease
      inactivation results from the reaction between allicin and the SH-group, situated
      in the urease active site (Cys592).

PMID- 14692510
TI  - Relationship between phosphatase activity and cytotoxic effect of two protein
      phosphatase inhibitors, okadaic acid and pervanadate, on human myeloid leukemia
      cell line.
AB  - Protein phosphatases are signalling molecules that regulate a variety of
      fundamental cellular processes including cell growth, metabolism and apoptosis.
      The aim of this work was to correlate the cytotoxicity of pervanadate and okadaic
      acid on HL60 cells and their effect on the phosphatase obtained from these cells.
      The cytotoxicity of these protein phosphatase inhibitors was evaluated on HL60
      cells using phosphatase activity, protein quantification and MTT reduction as
      indices. The major phosphatase presents in the cellular extract showed high
      activity (80%) and affinity (Km = 0.08 mM) to tyrosine phosphate in relation to p
      nitrophenyl phosphate (pNPP)-(Km = 0.51 mM). Total phosphatase (pNPP) was
      inhibited in the presence of 10 mM vanadate (98%), 200 microM pervanadate (95%)
      and 100 microM p-chloromercuribenzoate (80%) but okadaic acid caused a slight
      increase in enzyme activity (25%). When the HL60 cells were treated with the
      phosphatase inhibitors (pervanadate and okadaic acid) for 24hours, only 20%
      residual activity was observed in presence of 200 microM pervanadate, whereas in
      the presence of okadaic acid this inhibitory effect was not observed. However, in
      respect to mitochondrial function, cell viability decreased about 80% in the
      presence of 100 nM okadaic acid. The total protein content was decreased 25% when
      the cells were treated with 100 nM okadaic acid in combination with 200 microM
      pervanadate. Our results suggest that both phosphatase inhibitors presented
      different mechanisms of action on HL60 cells. However, their effect on the cell
      redox status have to be considered.

PMID- 14692511
TI  - Some 1,2-diphenylethane derivatives as inhibitors of retinoic acid--metabolising
      enzymes.
AB  - In a search for novel inhibitors of RA-metabolising enzyme inhibitors as
      potential anti-cancer agents some 1,2-ethandiones, 2-hydroxyethanones and 1
      ethylenedioxyethanones based on aryl-substituted 1,2-diphenylethane have been
      examined. Several of the compounds were weak inhibitors of the non-specific rat
      liver microsomal P450 enzymes and moderate inhibitors of the RA-induced enzymes
      in cultured human genital fibroblasts, where the RA-specific enzyme CYP26 is
      probably expressed. The 2-hydroxyethanone (13) with a 1-(4-dimethylaminophenyl)
      substituent was overall the most potent compound for rat liver microsomal enzyme
      (IC50 = 52.1 microM; ketoconazole, 2.8 microM) and the RA-induced enzyme (100
      microM, 65.9% inhibition; ketoconazole, 20 microM, 75.0%). Modification of the
      dimethylamino group in (13) with more hydrophobic dialkylamino functions or
      separate modification of the 2-(2,4-dichlorophenyl) function did not improve
      potency.

PMID- 14692512
TI  - Effect of L-arginine analogs and a calcium chelator on nitric oxide (NO)
      production by Leishmania sp.
AB  - Leishmania amazonensis, L. braziliensis and L. chagasi promastigotes were grown
      in the presence of L-arginine analogs such as Nomega-nitro-L-arginine methyl
      ester (L-NAME), NG-nitro-L-arginine (L-NNA) and D-arginine (an inactive L
      arginine isomer), besides an intracellular calcium chelator [ethylene glycol-bis
      (beta-aminoethyl ether)-N,N,N',N'-tetra acetic acid; EGTA] to verify the
      importance of L-arginine metabolism and the cofactors for these parasites. The
      parasite's growth curve was followed up and the culture supernatants were used to
      assay nitric oxide (NO) production by the Griess reaction. The results showed a
      significant effect of L-arginine analogs on NO production by all Leishmania
      species studied, especially L-NAME, an irreversible inhibitor of the constitutive
      nitric oxide synthase (cNOS). When L. amazonensis promastigotes were pre
      incubated with L-NAME, the infection range of the murine macrophages was lowered
      to 61% in 24 h and 19% after 48 h. These data demonstrated that the parasite NO
      pathway is important to the establishment of the infection.

PMID- 14692513
TI  - Binding of the human "electron transferring flavoprotein" (ETF) to the medium
      chain acyl-CoA dehydrogenase (MCAD) involves an arginine and histidine residue.
AB  - The interaction between the "electron transferring flavoprotein" (ETF) and medium
      chain acyl-CoA dehydrogenase (MCAD) enables successful flavin to flavin electron
      transfer, crucial for the beta-oxidation of fatty acids. The exact biochemical
      determinants for ETF binding to MCAD are unknown. Here we show that binding of
      human ETF, to MCAD, was inhibited by 2,3-butanedione and diethylpyrocarbonate
      (DEPC) and reversed by incubation with free arginine and hydroxylamine
      respectively. Spectral analyses of native ETF vs modified ETF suggested that
      flavin binding was not affected and that the loss of ETF activity with MCAD
      involved modification of one ETF arginine residue and one ETF histidine residue
      respectively. MCAD and octanoyl-CoA protected ETF against inactivation by both
      2,3-butanedione and DEPC indicating that the arginine and histidine residues are
      present in or around the MCAD binding site. Comparison of exposed arginine and
      histidine residues among different ETF species, however, indicates that arginine
      residues are highly conserved but that histidine residues are not. These results
      lead us to conclude that this single arginine residue is essential for the
      binding of ETF to MCAD, but that the single histidine residue, although involved,
      is not.

PMID- 14692514
TI  - Retinoic acid-induced cell cycle arrest of human myeloid cell lines.
AB  - Retinoic acid-induced terminal differentiation of myeloid cells involves the
      sequential regulation of cell cycle regulatory genes, coordinating the process of
      differentiation with arrest in the G0/G1 phase of the cell cycle. In this review
      we have summarized changes in expression and activity of cell cycle regulatory
      proteins associated with retinoic acid induced-growth arrest in human myeloid
      cell lines. These changes involve: (i) an early down-regulation of c-Myc; (ii) up
      regulation of p21CIP1 and p27KIP1 and, in some cases, p15INK4b or p18INK4c; (iii)
      down-regulation of cyclin E and cyclin D1/D3, and, at later stages, cyclin A and
      cyclin B; and (iv) decreased CDK activity and dephosphorylation of pRb.

PMID- 14692515
TI  - Effects of all-trans retinoic acid (ATRA) on human myeloma cells.
AB  - All-trans retinoic acid (ATRA) is a natural oxidative metabolite of Vitamin A
      (retinol) and is known to be a regulator of cell proliferation differentiation,
      especially in various malignant cells. The cyto-differentiating action of ATRA
      has led to its usage in the treatment of several malignancies, particularly acute
      promyelocytic leukemia (APL). There have been many reports regarding the cell
      biological effects of ATRA on human myeloma cells and a few clinical trials. Most
      of these reports have revealed growth inhibition by ATRA mediated by down
      regulation of the IL-6/IL-6R auto/paracrine loop, and upregulation of p21/Cip1.
      Here, we review previous reports and introduce experimental results obtained
      using various myeloma cell lines established in our laboratory.

PMID- 14692516
TI  - Dendritic cells and their potential therapeutic role in haematological
      malignancy.
AB  - The generation of an effective immune response is dependent on the efficient
      capture and presentation of antigen by antigen-presenting cells. The most potent
      antigen-presenting cells are dendritic cells (DC). These cells have the
      capability of activating naive helper and cytotoxic T cells. In recent years it
      has been demonstrated that in vivo responses to a number of solid tumours can be
      generated by DC pulsed with either purified tumour antigen or whole tumour cell
      lysate. In addition, a number of in vivo studies using DC have also been
      attempted in solid tumours, with some encouraging results. In haematological
      malignancies, there is now strong evidence that previous T cell anergy can be
      reversed and significant anti-tumour immune responses generated, in vitro,
      against the majority of leukaemias. As far as in vivo studies in haematological
      malignancies are concerned, although T cell responses have been demonstrated in
      the majority of cases and some dramatic early clinical responses reported,
      overall results appear disappointing. However, considering the fact that many of
      these studies were performed in patients with advanced disease and that such
      therapeutic strategies are still in their infancy, the overall results are
      actually quite encouraging. Although there is a real potential for DC
      immunotherapy in the future, it is important to be realistic about the
      limitations and obstacles to its development. It is highly unlikely that any form
      of immunotherapy is going to be effective in advanced disease due to the physical
      bulk of tumour, the immunosuppressive effects of tumours themselves and to any
      secondary immunosuppression following standard cancer therapy. The potential for
      immunotherapy is likely to lie either in adjunctive therapy or for treating
      minimal residual disease. Even in those situations, one of the major obstacles to
      be overcome is the state of immunological anergy or tolerance that many tumours
      seem able to induce. Indeed, there is evidence that, under certain circumstances,
      DC themselves can present antigen in such a way as to produce this state of
      anergy. Although, in vitro manipulation of DC and T cells can generate tumour
      specific T cells from previously "anergic" cells, once reintroduced in vivo,
      these cells will be re-exposed to the tumour environment with the risk of being
      rendered anergic again.

PMID- 14692517
TI  - Clonal cytotoxic T cells in myeloma.
AB  - Multiple myeloma (MM) is a malignant disease characterized by accumulation of
      morphologically recognizable plasma cells producing immunoglobulin (Ig) in the
      bone marrow. The occurrence of clonal T cells in MM, as defined by the presence
      of rearrangements in the T-cell receptor (TCR)-beta chains detected on Southern
      blotting, is associated with an improved prognosis. This review aims to describe
      the various ways in which we have demonstrated the presence of such T cell
      clones, and to describe the phenotype of these cells. Finally, the specificities
      of these clinically important CD8+ T cell populations will be discussed in the
      context of immunotherapy.

PMID- 14692518
TI  - ALK a novel lymphoma-associated tumor antigen for vaccination strategies.
AB  - The discovery of Tumor Associated Antigens (TAAs) demonstrated that tumor cells
      can be specifically recognized by the immune system raising the hypothesis that
      tumors express antigens that Cytotoxic T Lymphocytes (CTLs) can potentially
      attack. The identification of immunogenic epitopes led to their use as targets to
      mediate the specific clearance of neoplastic cells by TAA targeting strategies
      such as vaccination strategies. One of the critical issues in the development of
      efficient vaccination protocols is the identification of the appropriate TAAs.
      The TAA should be effective as a "tumor rejection antigen" able to induce an
      immune response that will affect tumor growth. A distinct pathologic entity
      characterized by the expression of the Anaplastic Lymphoma Kinase (ALK) protein
      and named "ALKoma" has recently emerged within the heterogeneous group of CD30+
      Anaplastic Large Cell Lymphoma (ALCL). ALK is a receptor tyrosine kinase whose
      expression is normally restricted to a few scattered cells in the nervous system.
      Its pathological expression in lymphoma cells is due to a chromosomal
      translocation that leads to the formation of an ALK-derived oncogenic fusion
      proteins. ALK fusion proteins ectopically over-expressed and constitutively
      activated in lymphoid cells play a key role in the neoplastic transformation by
      the aberrant phosphorylation of intracellular substrates that likely contributes
      to the molecular pathogenesis of ALCL. The high level of ALK expression in
      lymphoma cells and its direct role in lymphomagenesis, combined with the fact
      that normal ALK is expressed at low levels in the immune privileged nervous
      system, makes ALK an ideal lymphoma-specific target for immunotherapy of
      ALK+ALCL.

PMID- 14692519
TI  - Natural killer cell-triggering receptors in patients with acute leukaemia.
AB  - Human natural killer (NK) cells are potent effectors involved in destruction of
      virus infected cells and tumours. Their cytolytic function is regulated by
      surface receptors that either inhibit or increase the NK-mediated cytotoxicity.
      Under physiological conditions, NK cells recognize major histocompatibility
      complex (MHC)-class I molecules through surface receptors delivering signals that
      inhibit NK cells function. Nonetheless, the "missing self hypothesis", i.e. the
      release of an inhibitory signal by the interaction between HLA I-specific
      inhibitory receptors and their ligands, is not sufficient to entirely explain the
      regulation of NK cytotoxicity. Activating and co-receptors also play a central
      role in NK cell activation. In the haematology field, several lines of evidence
      suggest that NKs participate to the anti-leukaemia immune response: (1) leukaemic
      cells have down-regulated HLA-class I molecule expression and putative allele
      loss, (2) several reports have indicated an inverse relationship between NK cell
      number or activity and prognosis in acute leukaemia, (3) NK-cell activity
      dependent immunodeficiency syndromes are associated with an increased frequency
      of lymphoid haematological malignancies, (4) recent data support a role for NK
      cells in the graft-versus-leukaemia effect observed in allogeneic bone marrow
      transplantation. All these data raise several questions. How NK cells kill
      leukaemic targets, and how can leukaemia escape from innate immunity
      surveillance? What are the therapeutic possibilities to manipulate NK receptor
      ligand interaction in order to increase leukaemia cell destruction? The responses
      to these questions will contribute to immunotherapy advancements in leukaemia and
      more generally in cancer.

PMID- 14692520
TI  - Fixed-dose pegfilgrastim is safe and allows neutrophil recovery in patients with
      non-Hodgkin's lymphoma.
AB  - Twenty-nine patients with non-Hodgkin's lymphoma received a single subcutaneous
      injection of 6 mg pegfilgrastim approximately 24 h after the start of CHOP
      chemotherapy. The safety of pegfilgrastim in this patient population was
      determined by reports of adverse events. The pharmacokinetics of pegfilgrastim
      were characterized and the duration of grade 4 neutropenia, time to absolute
      neutrophil count (ANC) recovery to > or = 2.0 x 10(9)/l, neutrophil nadir, and
      incidence of febrile neutropenia were determined in the first 21-day chemotherapy
      cycle. The incidence of grade 4 neutropenia in cycle 1 was 43% with a mean (SD)
      duration of grade 4 neutropenia value of 1.0 (1.4) day. No apparent relationship
      between the duration of grade 4 neutropenia and body weight was observed. The
      median [quartiles] time to ANC recovery was 10 [9, 11] days. The incidence of
      febrile neutropenia was 11%. No unexpected adverse events were reported and no
      patient developed antibodies to pegfilgrastim. Serum concentration of
      pegfilgrastim reached a maximum (median [quartiles]) of 128 [58, 159] ng/ml at
      approximately 24 h after administration, and was followed by a second smaller
      peak (median [quartiles]) of 10.6 [3.0, 20.5] ng/ml at the time of the neutrophil
      nadir. After the second peak, concentration of pegfilgrastim declined linearly
      with a median terminal half-life of approximately 42 h.

PMID- 14692521
TI  - Current concepts of the immunobiology and immunotherapy of cutaneous T cell
      lymphoma: insights gained through cross-talk between the clinic and the bench.
AB  - An understanding of the immunologic features of cutaneous T cell lymphoma (CTCL)
      has led to insights into the life cycle of the malignancy. The identification of
      the T cell lineage of the neoplastic CTCL cells has allowed unification of
      diverse clinical presentations under a single entity. The CD4 inducer T cell
      phenotype of the malignant cells has provided an understanding of the patient's
      ability to resist infection with certain bacteria. The clonality of the tumor
      cells, beyond its diagnostic implications, has made them a valuable resource for
      studying both normal and neoplastic T cell biology. The recently identified
      immunosuppressive features of the malignant T cells and their dependency for
      survival on an interaction with immature dendritic cells have explained
      previously cryptic clinical observations and identified new targets for
      immunotherapy. Future insights gained both from the bedside and the bench will
      provide not only an understanding of the immunobiology of the malignancy but also
      open new avenues for therapeutic intervention.

PMID- 14692522
TI  - Pharmacological basis for cladribine resistance.
AB  - The inherent or acquired resistance of leukemic cells to cytostatic agents is a
      major clinical challenge. The purpose of this review was to elucidate and analyse
      the available data concerning mechanisms of resistance of cladribine with
      emphasis on recent advances in the characterization of activating and
      inactivating enzymes in the induction of resistance to cladribine. All available
      in vitro and clinical data on cladribine was undertaken. Cladribine, unlike many
      other drugs, is toxic to both dividing and indolent lymphoid malignancies.
      Cladribine is a prodrug and must be phosphorylated intracellularly to cladribine
      monophosphate (MP) by the nuclear/cystosol enzyme deoxycytidine kinase (dCK) and
      the mitochondrial enzyme deoxyguanosine kinase. The cytotoxicity mainly depends
      on the accumulation of cladribine-triphosphates (TP) after phosphorylation of
      cladribine-MP by nucleoside monophosphate kinase and nucleoside diphosphate
      kinase. 5'-Nucleotidase (5'-NT) dephosphorylates cladribine-MP and the
      accumulation of cladribine-TP depends on the ratio of dCK and 5'-NT in the cells.
      The mechanisms underlying cladribine resistance are multifactorial, e.g.
      decreased nucleoside transport, decreased activity or deficiency of dCK, altered
      intracellular pools of competing nucleotides, altered regulation of
      ribonucleotide reductase and increased drug inactivation by 5'-NT. Finally,
      cladribine resistance may be a consequence of a defective induction of apoptosis.
      In spite of the fact that more than one mechanism can contribute to a cladribine
      resistance phenotype, a reduction in dCK activity is probably the major
      determinant of cladribine resistance. Insight into the mechanism of action and
      resistance to cladribine is crucial for its optimal use as well as for the
      development of newer analogues.

PMID- 14692523
TI  - Acute myelogenous leukemia with t(8;21)--identification of a specific
      immunophenotype.
AB  - Association between certain surface markers and acute myelogenous leukemia (AML)
      with t(8;21) has been described. The specificity and the predictive values of
      these markers have never been assessed. In this study, we aimed, to explore
      whether a specific pattern could predict for this translocation. Of 405
      consecutive AML, 18 (4.4%) had the t(8;21). Patients with this cytogenetic
      abnormality showed higher frequency of CD34 (P = 0.003), HLA-DR (P = 0.03), Tdt
      (P = 0.02), CD19 (P < 0.0001), and CD56 (P < 0.0001) and lower CD33 (P = 0.0001).
      Taken singly, the sensitivity of these markers for AML with t(8;21) ranged
      between 39 and 100% with CD34+ having the highest and CD33- having the lowest and
      the positive predictive values (PPV) ranged between 5 and 21% with CD19+ having
      the highest and HLA-DR+ having the lowest. When combinations of different markers
      were analyzed by multivariate analysis, the pattern CD34+/HLA-DR+/MPO+ was found
      to have the highest sensitivity (100%) with a PPV of 14% and the pattern
      CD34+/CD19+/CD56+ had the highest PPV (100%) with a sensitivity of 67%. We
      conclude that AML with t(8;21) is better identified by a combination of markers
      than by a single antigen pattern, the absence of CD34+, HLA-DR+ or MPO+ would
      preclude and the expression of the pattern CD34+/CD19+/CD56+ is highly predictive
      and could serve as a screening criteria for the t(8;21).

PMID- 14692524
TI  - Anti-B4 blocked ricin post chemotherapy in patients with chronic lymphocytic
      leukemia--long-term follow-up of a monoclonal antibody-based approach to residual
      disease.
AB  - Anti-B4-blocked ricin is an immunotoxin consisting of anti-B4 murine monoclonal
      antibody and "blocked ricin" toxin. The anti-B4 monoclonal antibody is directed
      against the CD19 antigen, which is expressed on B-lymphocytes. A phase II study
      of anti-B4 blocked ricin toxin in patients with B-cell chronic lymphocytic
      leukemia (CLL) with residual disease after chemotherapy was conducted. Eleven
      patients received anti-B4 blocked ricin at 30 microg/kg lean body mass (LBM)
      daily by continuous infusion for 7 days followed with repeat infusion
      administered at 14-day intervals. No patient achieved an objective response. The
      major reasons for failure to respond were the presence of adenopathy and residual
      marrow disease. Three patients achieved immunophenotypic response in marrow and
      peripheral blood. Three of 6 patients with rearranged IgH and/or Ig kappa were
      germline after anti-B4 blocked ricin. The median follow-up of surviving patients
      is 8.6 years. The median survival is 5.8 years (range, 0.0-8.8). All patients
      have progressed. The median time to progression was 0.8 years (range, 0.3-3.0).
      Infusion-related toxicities were all grade 1-2. The most common toxicity was
      transaminitis. Human antimouse antibody (HAMA) and/or human antiricin antibody
      (HARA) development was documented in 2 patients. Anti-B4 blocked ricin was well
      tolerated but had limited activity in patients with residual CLL after
      chemotherapy.

PMID- 14692525
TI  - Anaplastic large cell lymphoma--a rare disorder in southern Taiwan.
AB  - Anaplastic large cell lymphoma (ALCL) is a subgroup of non-Hodgkin's lymphomas
      with large lymphoma cells expressing CD30 antigen. This entity has rarely been
      reported in Taiwan. We performed a retrospective clinicopathologic study in a
      medical center in southern Taiwan during a 13-year period and identified 13
      cases. There were 10 males and 3 females with a median age of 49 years old. Seven
      presented with pure nodal disease and 5 had bony involvement. The staging results
      were stage I (5 patients), II (1), III (1), and IV (4). The pathologic subtypes
      were common variant (10), lymphohistiocytic variant (2), and small cell variant
      (1). Eleven tumors were of T-cell lineage; 2, null-cell. Immunohistochemically, 5
      tumors (38.5%) expressed cytotoxic markers, T-cell intracellular antigen-1 and/or
      granzyme B. Two tumors (15.4%) expressed anaplastic lymphoma kinase (ALK). Long
      term follow-up information was available in 8 patients. The 2 patients with ALK
      expressing tumors (37 and 49 years old) were free of disease for 61 and 54
      months, respectively. The other 6 patients were either died of disease (5
      patients) or experienced relapse with progressive disease (1). In conclusion, we
      reported the largest series of ALCL in Taiwan. We confirmed ALK-expressing ALCL
      carries favorable prognosis and ALK-negative ALCL has similar poor prognosis as
      non-anaplastic T-cell lymphoma. As compared to the previous reports from the
      West, our ALK positive rate was lower and the age of our ALK-positive patients
      was older. A larger national or multi-institutional study is needed for further
      characterization of ALCL in Taiwan.

PMID- 14692526
TI  - Serum CA 125 as a prognostic factor in non-Hodgkin's lymphoma.
AB  - Cancer antigen 125 (CA 125) is a glycoprotein expressed in normal tissues
      originally derived from coelomic epithelia such as peritoneum, pleura,
      pericardium, fallopian tubes and endometrium. Serum CA 125 levels are elevated in
      various benign and malignant conditions that involve stimulation of these
      tissues. Although elevated levels have been reported in patients with non
      Hodgkin's lymphoma (NHL), its role as a prognostic factor remained uncertain. In
      this study, serum CA 125 levels were measured prospectively in 108 consecutive
      patients with NHL: at diagnosis in 106, in remission in 39 and at relapse in 7.
      Levels were elevated in 43% at diagnosis. This finding was associated with
      advanced disease stage, bulky tumors, bone marrow involvement, extranodal disease
      (in stages III and IV), occurrence of B symptoms, pleural or peritoneal
      effusions, high serum LDH levels, high serum beta2 microglobulin (beta2-M)
      levels, elevated International Prognostic Score, poor performance status and
      partial or no response to treatment. No difference in CA 125 level was found
      between the indolent and aggressive lymphomas. Serum CA 125 levels at diagnosis
      had strong association with event-free and overall survival (p = 0.01 and 0.003,
      respectively), with the patients with increased levels having worse survival.
      Patients with high CA 125 levels at diagnosis who achieved remission showed a
      significant decrease in CA 125 levels in remission. In conclusion, CA 125 is not
      only a reliable marker for staging and assessing tumor activity in NHL, elevated
      levels are also predictive of decreased survival.

PMID- 14692527
TI  - The CC genotype of the C825T polymorphism of the G protein beta3 gene (GNB3) is
      associated with a high relapse rate in patients with chronic lymphocytic
      leukaemia.
AB  - A C825T polymorphism has been described in the GNB3 gene which encodes the Gbeta3
      subunit of heterotrimeric G proteins. The GNB3 825T allele is predictive of
      enhanced Gi protein activation. This study was performed to correlate genotypes
      of the C825T polymorphism with various clinical aspects of chronic lymphocytic
      leukaemia (B-CLL). The GNB3 genotype distribution in B-CLL patients was similar
      to that in other Caucasian populations, arguing against a role of the
      polymorphism in the susceptibility to develop B-CLL. No statistically significant
      differences were observed at diagnosis between patients with the CC genotype and
      homozygous or heterozygous T allele carriers with respect to age at disease
      onset, sex distribution, proportion of patients with CD38+ leukaemia or patients
      in Binet stage A, blood cell counts, degree of bone marrow infiltration or serum
      levels of lactate dehydrogenase, thymidine kinase or beta2-microglobulin. In a
      subgroup of 44 patients requiring chemotherapy, the median interval between
      diagnosis and first treatment and the response to treatment were similar in
      patients with CC or CT/TT genotypes. A statistically significant difference,
      however, was found in the proportion of patients relapsing and requiring second
      line chemotherapy (CC: 95%; CT/TT: 52%; p = 0.0043). The GNB3 genotype (p =
      0.024) and age (p = 0.042) were identified as independent prognostic factors for
      a second therapy. Thus, the long-term success of the treatment appears to be
      correlated with the GNB3 genotype.

PMID- 14692528
TI  - Hepatitis C virus in patients with non-Hodgkin's lymphoma in southeastern
      Anatolia region of Turkey: a prospective case-control study of 119 patients.
AB  - Hepatitis C virus (HCV) has been associated with several extrahepatic disorders
      including mixed cryoglobulinemia (MC), autoimmune thyroiditis, Sjogren's
      syndrome. Such associations have led to the suggestion that HCV may participate
      in the development of various immunmediated disorders. Recently, it has been
      hypothesised that HCV might act as a trigger for the development of monoclonal B
      cell disorders such as non-Hodgkin's lymphoma (NHL). Discordant data have been
      reported in different geographic regions of the world. The aim of this
      prospective case-control study was to detect the prevalence of HCV in patients
      with NHL in southeastern Anatolia region of Turkey. In this study, HCV antibody
      prevalence and cryoglobulinemia were investigated in 119 patients with
      histologically diagnosed NHL. The control group consisted of 117 patients who
      visited the outpatient clinic of internal medicine. None of the patients had HCV
      antibody positive (0%) with the enzyme immunoassay and reverse transcriptase
      polymerase chain reaction (RT-PCR). One of the control patients had positive HCV
      antibody (0.9%). Our data does not support the association between HCV infection
      and NHL in southeastern Anatolia region of Turkey.

PMID- 14692529
TI  - POEMS syndrome: experience with fourteen cases.
AB  - The POEMS syndrome, also known as Crow-Fukase disease, is a rare multisystem
      disorder, which may take several years to evolve fully. The combination of
      symptoms and signs is highly complex and some of the features are detected at sub
      clinical level requiring high level of suspicion. The clinical data on POEMS is
      still evolving with only a few case reports from India. Herein, we report a
      series of 14 cases with POEMS syndrome at our centre over the past 8 years, which
      were analysed retrospectively for their clinical features, response to therapy
      and treatment outcome. Presence of plasma cell dyscrasia (PCD) was essential for
      inclusion in this study. Confirmation of PCD was done by positive "M" spike in
      serum and/or urine, bone marrow plasmacytosis or presence of plasmacytoma on
      biopsy. In addition, the diagnosis of POEMS syndrome needed the presence of at
      least two of the following features: polyneuropathy, organomegaly, endocrinopathy
      and/or skin changes. Patients were excluded from study if there was a secondary
      cause of polyneuropathy like amyloidosis, drugs like vincristine, nerve root or
      spinal cord compression. Two patients had complete form (all five features) of
      the syndrome, whereas 12 had incomplete form. Median age was 48 years (range 32
      65). Peripheral neuropathy was seen in 13 (92.85%) cases, organomegaly 10
      (71.42%), endocrinal involvement 7 (50%) and skin changes 9 (64.28%). An
      association with Castleman's disease and vasculitis was also noted. With
      different chemotherapy protocols, all treated patients (n = 12), had significant
      symptomatic improvement with or without objective improvement at median follow up
      of 48 months (range 6-120). In conclusion, high level of suspicion is required to
      detect this rare entity.

PMID- 14692530
TI  - Granulocytic sarcoma: an unusual complication of aleukemic myeloid leukemia
      causing spinal cord compression. A case report and literature review.
AB  - Granulocytic sarcoma (chloroma) is a rare solid tumor resulting from the
      proliferation of myelogenous leukemia cells. Chloromas usually present as soft
      tissue or bony masses of the head and neck in patients with acute myelogenous
      leukemia (AML) of the French-American-British M2 subtype. Occasionally chloromas
      may occur in patients with myelodysplasia and other myeloproliferative disorders
      and rarely precede the development of systemic disease. It is distinctly rare for
      such tumors to cause epidural compression as a first manifestation of disease.
      Herein, we report the case of a man with a thoracic extradural chloroma whose
      presentation of progressive lumbar pain ultimately led to the diagnosis of M2
      AML. Surgical intervention prior to the onset of paraplegia and the prompt
      initiation of chemotherapy resulted in an excellent neurological and
      hematological outcome. We also review the literature of previously reported cases
      of spinal cord-associated chloroma and focus on the clinical presentation and
      treatment of this disorder.

PMID- 14692531
TI  - C-MAF oncogene dysregulation in multiple myeloma: frequency and biological
      relevance.
AB  - To investigate the frequency and possible biological consequences of c-maf
      dysregulation, we designed c-maf and IL-4 real-time RT-PCR assays for
      determination of c-maf and IL-4 mRNA levels. Using the c-maf real-time RT-PCR
      assay, we tested a panel of 14 B-cell lines, 135 diagnostic bone marrow (BM)
      samples from patients with multiple myeloma and 10 BM samples from normal donors.
      In B cell lines and flowsorted CD38++/CD19-/CD56++ myeloma plasma cells (N = 14)
      the c-maf/GAPDH and IL-4/GAPDH ratios were determined simultaneously using real
      time RT-PCR. All B cell lines used in the study were characterized by flow
      cytometry and tested for the presence of Ebstein-Barr virus (EBV). B-cell lines,
      that were PCR negative for EBV and had a phenotype typical for primary myeloma
      cells, expressed medium to high levels of c-maf mRNA. However, all EBV PCR
      positive cell lines, showed a more immature phenotype, lacked expression of
      aberrant surface markers and contained very low levels of c-maf mRNA. In 4.4%
      (6/135) of MM patients tested, a c-maf mRNA level comparable to the cell line
      RPMI 8226 containing at (16:22), translocation was found. In addition, all c-maf
      positive myeloma cell lines and CD38++/CD19-/CD56++ myeloma plasma cells tested
      were IL-4 negative. In conclusion, high levels of c-maf mRNA were observed in
      "true MM cell lines" and 4.4% of MM patients. Further, c-maf dysregulation in
      myeloma plasma cells did not cause induction of IL-4 transcription.

PMID- 14692532
TI  - Gamma-irradiation enhances apoptosis induced by cannabidiol, a non-psychotropic
      cannabinoid, in cultured HL-60 myeloblastic leukemia cells.
AB  - Two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabidiol
      dimethylheptyl (CBD-DMH), induced apoptosis in a human acute myeloid leukemia
      (AML) HL-60 cell line. Apoptosis was determined by staining with bisBenzimide and
      propidium iodide. A dose dependent increase of apoptosis was noted, reaching 61
      and 43% with 8 microg/ml CBD and 15 microg/ml CBD-DMH, respectively, after a 24 h
      treatment. Prior exposure of the cells to gamma-irradiation (800 cGy) markedly
      enhanced apoptosis, reaching values of 93 and 95%, respectively. Human monocytes
      from normal individuals were resistant to either cannabinoids or gamma
      irradiation. Caspase-3 activation was observed after the cannabinoid treatment,
      and may represent a mechanism for the apoptosis. Our data suggest a possible new
      approach to treatment of AML.

PMID- 14692533
TI  - Improved therapeutic outcome following combination immunogene vaccination therapy
      in murine myeloma.
AB  - Increasing evidence suggests a role for immunologic vaccination and therapy in
      the management of minimal residual myeloma. We have previously demonstrated a
      synergistic effect of combining the Th1 stimulating cytokine IL-12 with the co
      stimulatory molecule CD80 in murine myeloma vaccination therapy. We reasoned that
      the efficacy of such treatment might be further improved by incorporating
      additional gene products which enhance the function of antigen presenting cells.
      Studies were therefore conducted with murine myeloma BM1 cells expressing Flt3L
      (membrane bound or soluble forms) or GM-CSF and the IL-12 x CD80 combination.
      Single agent and combined therapeutic approaches were explored. All gene-modified
      BM1 cells, except BM1/IL-12 x CD80, developed tumors when subcutaneously injected
      into BALB/c mice. As prophylactic tumor vaccines, the combined use of gene
      modified BM1/sFlt3L+GM-CSF+IL-12 x CD80 was most effective, providing 100%
      protection against subsequent parental BM1 tumor challenge. By comparison, only
      partial protection was observed with any single gene-engineered tumor vaccine.
      Notably, IL-12 x CD80 coexpressing BM1 cell vaccines were the most effective
      therapeutic vaccine in a minimal disease model. Such protective vaccination was
      achieved by stimulation of lymphocyte proliferation and enhancement of cytotoxic
      lymphocyte activity.

PMID- 14692534
TI  - Phytohemagglutinin inhibits lymphoid tumor growth in vitro and in vivo.
AB  - Cure rates for a variety of leukemias and lymphomas have improved dramatically
      over the past several decades, but relapsed disease continues to account for
      thousands of deaths per year. Viable treatment options for relapsed disease are
      few, encouraging the development of novel therapies. In the present paper, we
      describe phytohemagglutinin (PHA), a standard T cell mitogen, as an inhibitor of
      both T- and B-cell tumors. In vitro studies show that PHA can inhibit
      incorporation of 3H-thymidine and mediate apoptosis of B- and T-cell tumor lines.
      The inhibitory effects are enhanced when PHA is used in conjunction with the cell
      cycle directed drug 5-fluorouracil (5-FU). Phytohemagglutinin treatments can also
      impede tumor growth in mice while showing no toxic side effects in this animal
      model.

PMID- 14692535
TI  - Varicella-zoster viral meningitis mimicking lymphoma.
AB  - We report the case of a 30-year-old HIV-infected man admitted for a meningeal
      syndrome and a zoster rash. The CSF had cytological features suggesting a primary
      CNS lymphoma (PCNSL). The large lymphoid cells had a fine chromatin with
      nucleoli, a basophilic cytoplasm with azurophilic granules and high mitotic
      activity. Several arguments demonstrated the viral origin of the meningitis: the
      large lymphoid cells were of T origin with no evidence of clonal TCR gamma gene
      rearrangement. The PCR was positive for Varicella-Zoster Virus (VZV) and EBV DNA.
      Clinical evolution was favorable under acyclovir. We should be cautious in the
      differential diagnosis between viral meningitis and PCNSL.

PMID- 14692536
TI  - Adult hypocellular acute leukaemia with lymphoid differentiation.
AB  - The rare hypocellular variants of acute leukemia (AL) previously also termed
      smouldering leukemia, almost always exhibit myeloid differentiation. Very rare
      cases of hypocellular AL with lymphoid differentiation have been reported,
      usually in children. This paper describes two cases (an 87-year-old woman and a
      79-year-old man) in whom the blood findings were suggestive of AL. Paraffin
      embedded bone marrow biopsy specimens revealed similar findings in both patients:
      there was severe hypocellularity, the cells of normal hemopoiesis were greatly
      reduced in number, and there was a diffuse increase in blast cells, which
      represented more than 50% of nucleated marrow cells. The blasts coexpressed TdT
      and CD34 and were negative for myeloperoxidase, CD117, CD68 and naphthol AS-D
      chloroacetate esterase. For the first time immunohistochemical Pax-5/CD34
      doublestainings are provided, which revealed the blasts in one case to coexpress
      Pax-5 and CD34. All the blasts were CD79a-positive and 20% were also CD10
      positive. In the other case, 20% of the blasts were CD79a-positive, 30%
      coexpressed Pax-5 and CD34 by doublestaining, and showed a clonal rearrangement
      of the immunoglobulin heavy chain gene. Thus a diagnosis of AL of lymphoid
      lineage, hypocellular variant, was made on the basis of immunohistochemical
      findings. The clinical course appears to be similar to that of hypocellular AML,
      as neither patient has developed overt leukemia during the one-year follow-up
      period.

PMID- 14692537
TI  - Fatal hemophagocytic syndrome in a patient with panniculitis-like T-cell lymphoma
      and no clinical evidence of disease.
AB  - Panniculitis-like T-cell lymphoma is an uncommon type of extranodal T-cell
      lymphoma which presents clinically with subcutaneous nodules. The clinical course
      can either be indolent or rapidly progressive, often complicated by
      hemophagocytic syndrome. We report a patient with primary subcutaneous disease
      and initial complete response to combination chemotherapy. The patient
      experienced an early relapse which responded to salvage chemotherapy. However,
      she died shortly thereafter with hemophagocytic syndrome, polymicrobial sepsis
      and systemic fungal infection. At autopsy there was no evidence of lymphoma in
      the bone marrow or other organs. We emphasize that a fatal hemophagocytic
      syndrome can occur despite minimal or even without evidence: of clinically active
      lymphoma as demonstrated by autopsy in this case.

PMID- 14692538
TI  - Effective anti-viral therapy for hemophagocytic syndrome associated with B-cell
      lymphoma.
AB  - A rheumatoid arthritis (RA) patient treated with low-dose methotrexate (MTX)
      therapy suffered from hemophagocytic syndrome (HPS) associated with B-cell
      lymphoma (B-LAHS). Administration of acyclovir and intravenous immunoglobulin
      promptly resolved laboratory test abnormalities accompanied with HPS. Moreover,
      hemophagocytic histiocytes and lymphoma cells in the bone marrow disappeared
      without anti-cancer therapy. Two months after reintroduction of MTX for RA flare,
      lymphoma re-grew rapidly without bone marrow involvement and HPS. Two cycles of
      combination chemotherapy induced the lymphoma to a complete remission/unconfirmed
      (CRu), but then the chemotherapy was discontinued due to severe side effects. In
      this case, on the basis of RA and MTX induced immunosuppressive state, Epstein
      Barr virus (EBV) infection was associated with the development of HPS and
      lymphoma. Anti-viral therapy alone was effective against HPS and lymphoma at
      initial presentation and improved her general condition. This case indicates that
      anti-cancer therapy should be preceded by anti-viral therapy and withdrawal of
      immunosuppressive therapy in patients under immunosuppressive therapy, as long as
      the clinical situation permits.

PMID- 14692539
TI  - HIV and HHV-8 negative primary effusion lymphoma in a patient with hepatitis C
      virus-related liver cirrhosis.
AB  - Primary effusion lymphoma (PEL) or body cavity-based lymphoma (BCBL) is a unique
      subgroup of B-cell lymphomas that exhibits exclusive or dominant involvement of
      serous body cavities without a detectable tumor mass. We present a case of a
      PEL/BCBL that exclusively involved the peritoneal cavity of a 58-year-old
      immunocompetent male with hepatitis C virus (HCV)-related liver cirrhosis. The
      lymphoma cells were large, highly atypical and expressed CD19, CD20, CD22, CD10,
      HLA-DR, and CD45 with kappa light chain restriction. Unlike typical PEL/BCBL,
      human herpesvirus type 8/Kaposi sarcoma herpes virus (HHV-8/KSHV) genomic
      sequence was not present in the lymphoma cells and there was no serologic
      evidence of human immunodeficiency virus (HIV) infection. This is the fourth
      reported case of HHV-8 negative, HIV negative PEL/BCBL in a patient with
      associated HCV-related cirrhosis and review of these cases showed some consistent
      clinicopathological features, i.e. exclusive involvement of the peritoneal cavity
      and phenotypic expression of B-cell associated antigens in contrast to the
      generally null phenotype PEL/BCBL. The occurrence of these cases suggests that
      HCV may play an etiological role in a subcategory of PEL/BCBL not associated with
      HHV-8.

PMID- 14692540
TI  - Progressive multifocal leukoencephalopathy with detection of JC virus in a
      patient with chronic lymphocytic leukemia parallel to onset of fludarabine
      therapy.
AB  - Along with the establishment of more intense chemotherapeutic regimens including
      fludarabine for the treatment of indolent lymphoproliferative diseases like
      chronic lymphocytic leukemia (CLL), an increasing amount of cases with
      progressive multifocal leukoencephalopathy (PML) due to JC virus have been
      observed. We report a patient with CLL who developed PML parallel to the onset of
      fludarabine therapy. Spinal fluid was tested positive for JC virus. Despite
      virostatic treatment with cidofovir, neurologic symptoms were progressive and the
      disease ultimately fatal. The present case suggests that immunosuppression caused
      by chronic lymphoproliferative malignancies alone may be a factor in the
      development of PML. Chemotherapy with fludarabine may act as an additional
      trigger. The question remains whether serologic screening for JC virus in
      patients with chronic lymphoproliferative disease undergoing intense chemotherapy
      might be valuable once sufficient antiviral treatment has been established.

PMID- 14692541
TI  - Progressive multifocal leukoencephalopathy complicating Waldenstrom's
      macroglobulinaemia.
AB  - Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating
      neurological disorder caused by JC virus. Immunocompromised patients such as
      those with chronic lymphocytic leukemia, AIDS and following organ transplantation
      are at increased risk. We report a patient with PML complicating longstanding
      Waldenstrom's macroglobulinaemia. Although PML is a rare occurrence, the newer
      highly immunosuppressive treatment approaches for patients with
      lymphoproliferative disorders necessitate a high index of clinical suspicion. The
      diagnosis should be considered in patients with compatible clinical features who
      have received long-term immunosuppressive treatments recognized to impair
      cellular immunity.

PMID- 14692542
TI  - Fibrous dysplasia masquerading as extramedullary relapse after bone marrow
      transplantation for chronic myeloid leukemia.
AB  - A 19-year old girl suffered from relapse of chronic myeloid leukemia (CML) after
      bone marrow transplantation. The disease was controlled by interferon and
      imatinib mesylate, but was complicated by autoimmune hyperthyroidism. She
      presented with unilateral proptosis with no extraocular muscle or visual defect
      at 26 months follow-up. Systemic investigations showed no recurrence of leukemia
      or thyrotoxicosis. Magnetic resonance imaging revealed an extensive retro-orbital
      base of skull lesion. A trans-oral biopsy showed fibrous dysplasia and continuous
      observation was advised. The unusual sequence of events and the differential
      diagnoses for unilateral proptosis in post bone marrow transplantation (BMT)
      cases are discussed.

PMID- 14692543
TI  - Guillain-Barre syndrome and myelodysplasia--a possible association.
AB  - We report on three cases of Guillain-Barre syndrome (GBS) occurring in patients
      with myelodysplasia, two with autoimmune manifestations. In two cases the
      myelodysplasia was diagnosed during the treatment of the GBS, while in the third
      case the myelodysplasia preceded its diagnosis. We discuss possible underlying
      mechanisms for the previously unreported finding.

PMID- 14692544
TI  - Fine-needle aspiration cytology of a para-aortical solitary plasma-cell tumor.
AB  - Extramedullary plasma-cell tumor (EMP) is a very rare disease and mainly arises
      in the head and neck area. An EMP arising in the paraaortical space was diagnosed
      by fine needle aspiration cytology and immunocytochemistry, in a 48-year-old
      male. Smears were cellular and showed dissociated monomorphic plasma cells.
      Immunocytochemistry demonstrated monoclonal expression of kappa-light
      immunoglobulin chain and CD38 positivity. Cytomorphology and immunocytochemical
      profile allowed a definitive diagnosis of plasmacytoma.

PMID- 14692545
TI  - Fatal fludarabine-induced extensive bone marrow necrosis in a patient with
      chronic lymphocytic leukemia.

PMID- 14692546
TI  - Importance of combined-modality therapy for primary bone lymphoma.
AB  - Primary bone lymphoma (PBL) is a rare entity and comprises about 5% of all
      extranodal non-Hodgkin's lymphomas (NHL) and 7% of all primary bone tumors. To
      date there is no consensus about the optimal treatment for PBL. We
      retrospectively reviewed all cases of PBL treated at Hospital Sao Paulo, Brazil,
      over a 10-year-period (January 1992-January 2002). Medical records of 7 patients
      with PBL were reviewed and information on age at diagnosis, sex, NHL clinical
      staging (CS), treatment and response to treatment were retrieved. Five patients
      (72%) received combined-modality therapy (CMT) and all of them are in complete
      remission (CR) with a median follow up of 19 months (ranging from 12 to 144
      months). We conclude that PBL is a potentially curable malignancy and treatment
      should be undertaken in a multiprofessional approach, in order to provide the
      best support which probably has to include chemotherapy, radiotherapy and, for
      patients with IPI higher than 2, consolidation with stem-cell transplantation.

PMID- 14692547
TI  - What is your diagnosis? Ocular lymphoma.

PMID- 14692548
TI  - Comparison of three distraction methods and conventional radiography for early
      diagnosis of canine hip dysplasia.
AB  - Two radiographic distraction techniques (one employing a wooden lath and, the
      other, a PennHip distractor), an ultrasonographic distraction method and
      conventional radiographic Federation Cynologique Internationale (FCI) hip score
      were evaluated in eight-month-old Labrador retrievers to determine the most
      reliable method for predicting radiographic FCI hip score at the age of one year.
      With reference to the FCI hip score, sensitivity and specificity of the PennHip
      method were 100 per cent and 54 per cent; sensitivity and specificity of the lath
      technique were 85 per cent and 71 per cent; whereas they were 62 per cent and 67
      per cent for the ultrasonographic method. For all distraction methods, the
      positive predictive value (PPV) was moderate and the negative predictive value
      (NPV) was high. Sensitivity, specificity, PPV and NPV were 100 per cent for the
      FCI hip score. It is concluded that, at the age of eight months, FCI hip score is
      the most reliable method for predicting FCI hip score at the age of one year in
      the colony of dogs investigated. Both the PennHip and lath method were also
      clinically reliable techniques in predicting true negatives. The ultrasonographic
      distraction method was moderately reliable.

PMID- 14692549
TI  - Assessment of a pyrogallol red technique for total protein measurement in the
      cerebrospinal fluid of dogs.
AB  - The measurement of protein concentration in the cerebrospinal fluid is a basic
      analytical method in neurology. In this study, a pyrogallol red technique using a
      human albumin calibrator previously validated in human medicine was tested for
      canine samples, and the results were compared with those obtained using urine
      test strips. Pyrogallol red significantly (P<0.05) but moderately underestimated
      purified dog albumin and globulins. The imprecision of the technique was low:
      intra- and between-series coefficients of variation were 1.6 and 4.3 per cent at
      protein concentrations of about 0.3 g/litre. Over 49 samples, there was good
      agreement between the pyrogallol red and test strip results (r=0.63), especially
      for low and high protein concentrations, but misclassifications were observed
      with '+' test strip readings.

PMID- 14692550
TI  - Simultaneous use of bilateral caudal superficial epigastric axial pattern flaps
      for wound closure in a dog.
AB  - A neutered male German shorthaired pointer sustained severe bite wounds to the
      left caudal flank and thigh area. Thorough wound lavage and debridement was
      performed immediately and also three days after presentation. Daily wound
      dressing resulted in the production of a mature granulation tissue bed. Prior to
      wound closure, colour flow Doppler ultrasonography was used to confirm blood flow
      through the right and left caudal superficial epigastric arteries and veins.
      Sixteen days after presentation, right and left caudal superficial epigastric
      axial pattern flaps were simultaneously elevated to cover the defect. The right
      flap was elevated as an island flap, rotated 120 degrees and used to cover the
      caudodorsal aspect of the defect. The left flap was elevated and rotated dorsally
      to cover the cranioventral aspect of the defect. Ninety per cent wound coverage
      was achieved and flap survival was total. The donor site defect was closed
      primarily and no dehiscence occurred. Three months postsurgery, the entire defect
      was closed and limb function was normal.

PMID- 14692551
TI  - Treatment of bicipital tenosynovitis with double tenodesis.
AB  - This report describes two dogs with bilateral bicipital tenosynovitis which were
      managed using double tenodesis. Surgical repair involved the attachment of the
      tendon to the humerus with a bone screw and plastic spiked washer, and a double
      Bunnell-Meyer suture. Six months postoperatively, neither of the treated dogs
      displayed any lameness on clinical examination.

PMID- 14692552
TI  - Maxillary bone epithelial cyst in a dog.
AB  - A swelling ventromedial to the left eye of a one-year-old, neutered male Labrador
      failed to respond to antibiotic and anti-inflammatory therapy. Plain and contrast
      radiography revealed a spherical, radiolucent area, 1.5 cm in diameter,
      dorsomedial to the fourth maxillary premolar and rostral to the ethmoid region.
      The lesion was thin-walled, with a smooth radiopaque margin, and was clearly
      demarcated from the surrounding structures. Dacryocystography demonstrated no
      apparent physical association between the lesion and the nasolacrimal duct, the
      latter appearing normal. Ultrasonography of the lesion showed a round, anechoic
      structure consistent with the appearance of a cyst. Prior to surgical excision of
      the lesion, intralesional fluid was aspirated. Bacteriology of the fluid was
      negative for both aerobic and anaerobic organisms. Cytological examination of the
      fluid showed a few macrophages and small lymphocytes; neither significant
      inflammatory component nor neoplastic cells were found. Histology showed the
      lesion to be a benign epithelial cyst. The dog recovered uneventfully and there
      was no clinical evidence of recurrence within a two-year follow-up period.

PMID- 14692553
TI  - Resolution of chylothorax after resection of rib chondroma in a dog.
AB  - A six-year-old, male dobermann was presented with a history of dyspnoea and bouts
      of coughing. Radiography and computed tomography of the thorax showed pleural
      effusion and a well-circumscribed, calcified mass of 10 cm in diameter, appearing
      to originate from the left first rib. Thoracocentesis revealed that the pleural
      fluid was chylous in nature. An incisional biopsy was performed, which gave a
      histological diagnosis of chondroma. Resolution of the chylothorax after en-bloc
      surgical removal of the tumour suggested that the rib tumour was the initiating
      cause of the chylothorax. Seventeen months later, rib neoplasia recurred without
      pleural effusion, and was removed successfully. To the authors' knowledge, rib
      chondroma, which is an unusual tumour in dogs, has not been previously documented
      as a cause of chylothorax.

PMID- 14692554
TI  - Laminin alpha2 deficiency-associated muscular dystrophy in a Maine coon cat.
AB  - A European case of laminin alpha2 deficiency-associated muscular dystrophy in a
      12-month-old, female Maine coon pedigree cat is reported. The history and
      eventual clinical presentation of this cat differed from those of two cats
      reported in the USA. In this case, the myopathy was characterised by
      progressively worsening weakness, muscle atrophy and joint contracture. Tendon
      reflexes were diminished, and motor nerve conduction velocities were slowed.
      Muscle biopsy demonstrated a dystrophic phenotype with endomysial fibrosis.
      Occasional thinly myelinated nerve fibres were present within a peripheral nerve
      specimen. Poorly myelinated fibres were also found at the root level on necropsy
      specimens. Immunohistochemical staining revealed the absence of laminin alpha2.
      The cat's family history did not indicate genetic transmission of the disease.

PMID- 14692555
TI  - Congress 2004: geriatric cats and feline infectious diseases.

PMID- 14692556
TI  - Equipping vets to deal with animals' dental health needs.

PMID- 14692557
TI  - Can high resolution computed tomography predict lung function in patients with
      chronic obstructive pulmonary disease?
AB  - High-resolution computed tomography (HRCT) is a useful method for quantifying the
      extent of emphysema. Few reports have mentioned the relationships between HRCT
      scans and pulmonary function tests in chronic obstructive pulmonary disease
      (COPD). For diagnosis, COPD requires chronic airflow limitation and emphysema
      and/or chronic bronchitis. We examined 20 who were previous smokers with middle
      to moderate COPD. All were normocapnic with mean arterial oxygen pressure (PaO2)
      77,52 +/- 16,789 mmHg. Forced spirometry, somatic plethysmography and
      cardiopulmonary exercise test were performed in each patient. HRCT was performed
      in both full inspiration and full expiration at three levels through the upper
      (at the aortic arch), lower (2 cm above the diaphragm), and middle lung (midpoint
      between upper and lower) levels. During expiration all pulmonary function
      parameters correlated with the HRCT grade in the middle right and left part of
      the lungs. The middle right part of the lung during expiration correlated
      statistically significant with MVV (r = -0.681, p = 0.001), forced vital capacity
      (FVC) (r = -0.477, p = 0.027), forced expiratory volumein 1 sec (FEV1) (r = 
      0.632, p = 0.002), resistance (r = 0.674, p = 0.001), residual volume (RV) (r =
      0.733, p = 0.001), total lung capacity (TLC) (r = 0.696, p = 0.001), functional
      residual capacity (FRC) (r = 0.752, p = 0.001) and peak oxygen consumption during
      exercise (VO2) (r = -0.493, p = 0.023). The middle left part of the lung during
      expiration correlated statistically significant with MVV (r = -0.673, p = 0.001),
      FVC (r = -0.493, p = 0.027), FEV1 (r = -0.629, p = 0.003), resistance (r =
      0.593,p = 0.005), RV (r = 0.601, p = 0.005), TLC (r = 0.546, p = 0.012), FRC (r =
      0.594, p = 0.006) and peak VO2 (r = -0.525, p = 0.015). Forced expiratory volume
      in 1 sec (FEV1), which is a well-established measure of airflow obstruction,
      correlated with the HRCT grade (1) in the middle left part of the lung during
      inspiration (r = -0.468, p = 0.035) and during expiration (r = - 0.629, p =
      0.003) (2) in the lower right lung during inspiration (r = -0.567, p = 0.007) and
      during expiration (r = -0.558, p = 0.008) (3) in the lower left lung during
      inspiration (r = -0.542, p = 0.011) and during expiration (r = -0.558, p = 0.008)
      (4) in the upper right lung during expiration (r = -0.469, p = 0.037) (5) in the
      upper left lung during expiration (r = -0.463, p = 0.035) and (6) in the middle
      right lung during expiration (r = -0.632, p = 0.002). According to our results
      HRCT was a valuable tool for evaluating the severity of COPD--especially the
      middle right and left part of the lungs, during expiration--and correlated well
      with pulmonary function tests.

PMID- 14692558
TI  - Optical feedback training of inhalation with Autohaler and Turbuhaler in COPD
      patients.
AB  - The success of inhalation therapy depends on patients inhalation technique and
      correct handling of the inhalation device. In this study the effort to train
      correct handling and optimal inhalation technique of patients using Autohaler and
      Turbuhaler was assessed. The Bad-Reichenhall-Aerosol-Therapy-Trial (BREATH) was a
      prospective, randomized, cross-over trial in 200 patients who were not familiar
      with either of the test systems. The correct handling of Autohaler and Turbuhaler
      was assessed by means of a checklist (observation score). An optimal inhalation
      maneuver was used evaluated with the computer-based Inhalation Manager (optical
      feedback, computer score). The Autohaler reached 6.58 +/- 3.64 (mean +/- SD) out
      of nine points in the observation score and 66.85 +/- 29.84% in the computer
      score before training. After training the scores increased significantly to 8.33
      +/- 2.08 points and 86 +/- 23.40% respectively. The use of the Turbuhaler also
      significantly improved from 4.28 +/- 4.24 points and 56.67 +/- 42.97% to 7.78 +/-
      2.74 points and 85.80 +/- 27.63%, respectively. The significant improvement of
      patients inhalation technique after training emphasizes the importance of
      training in inhalation therapy. In addition, it could be demonstrated that the
      optical feedback given by the Inhalation Manager was a useful tool for improving
      the inhalation technique of patients using Autohaler and Turbuhaler.

PMID- 14692559
TI  - Expression of KIT (CD117) in biphasic pulmonary blastoma. Novel data on
      histogenesis.
AB  - Biphasic pulmonary blastoma (BPB) is a rare primary neoplasm of the lung and its
      histogenesis is still uncertain. It has been proposed that BPB is derived from
      mesoderm or endoderm. Others suggested an origin from a single pluripotential
      cell. We present a case of a BPB with emphasis on expression of the stem cell
      factor receptor KIT (CD117). We describe a 61-year-old male patient with a BPB of
      the upper right lobe. Immunohistochemical analysis was performed using a panel of
      several antibodies including anti-CD117. Strong cytoplasmic expression of CD117
      was found in the epithelium (cytokeratin-positive) as well as in the spindle
      cells (cytokeratin-negative). Expression of CD117 in both mesenchymal and
      epithelial cells suggests a single origin and supports the idea that BPB arises
      from a pluripotential cell that can differentiate into both stromal and
      epithelial morphologies. The role of CD117 in the pathogenesis of BPB and its
      possible therapeutic relevance require further investigation.

PMID- 14692560
TI  - Effect of inhaled racemic and (R)-albuterol on airway vascular smooth muscle tone
      in healthy and asthmatic subjects.
AB  - Although the relative effect of racemic and (R)-albuterol on airway smooth muscle
      tone have been investigated in patients with airflow obstruction, the comparative
      effectiveness of these drugs in relaxing airway vascular smooth muscle is
      unknown. Therefore, we determined the actions of inhaled racemic and (R)
      albuterol on airway mucosal blood flow (Qaw) normalized for anatomic dead space
      as an index of airway vascular smooth muscle tone in 11 healthy subjects and 10
      subjects with mild asthma. We also monitored the forced expiratory volume in 1
      second (FEV1) as an index of airway smooth muscle tone. Mean +/- SE baseline Qaw
      was 43.1 +/- 1.5 microl x min(-1) x ml(-1) in healthy subjects and 53.4 +/- 2.1
      microl x min(-1) x ml(-1) in asthmatic subjects (p < 0.01). The corresponding
      values for FEV1 were 95.6 +/- 1.4 and 86.8 +/- 2.5% respectively, of predicted (p
      = 0.01). Racemic and (R)-albuterol caused a transient, dose-dependent increase of
      Qaw in healthy, but not in asthmatic subjects; the responses were not different
      between the two drugs. The FEV1 tended to increase more in asthmatics than in
      healthy subjects, again without a difference between the two drugs. These results
      show that racemic and (R)-albuterol have comparable effects on airway vascular
      smooth muscle and suggest that the blunted airway vascular smooth muscle response
      to albuterol in asthmatics is not related to (S)-albuterol.

PMID- 14692561
TI  - Platelet activating factor in surfactant-TA is inhibited by coexisting
      inhibitors.
AB  - To clarify whether or not the platelet activating factor (PAF) present in
      surfactant-TA (calf-lung extract) is harmful, we investigated the activity and
      inhibitory activity of PAF in a surfactant preparation using a bioassay with
      washed rabbit platelets. The surfactant-TA contained PAF at 11-21 pmol/vial. The
      fractions of lysophosphatidylcholine, sphingomyelin, phosphatidylserine plus
      phosphatidylinositol, and phosphatidylglycerol dose-dependently inhibited the
      aggregation of washed rabbit platelets induced by PAF. Surfactant-TA contained
      sufficient amounts of these phospholipids to inhibit the PAF activity completely.
      These results suggest that coexisting PAF inhibitors protect the lung from the
      harmful effects of PAF in surfactant-TA.

PMID- 14692562
TI  - HnRNP A2/B1 proteins in nontumorous alveolar cells.
AB  - The overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1,
      especially of B1, had been reported to detect preclinical lung cancer for early
      detection. In order to examine whether the expression of the protein is specific
      for lung cancer, we investigated the expression of the protein in human
      nonmalignant alveolar cells. Human airway cells obtained by bronchoalveolar
      lavage (BAL) were analyzed by immunostaining and Western blotting using
      monoclonal antibodies 4G8 (specifically reacts to A2) and 2B2 (specific to B1).
      In alveolar cells obtained by BAL, hnRNP A2/B1 proteins were localized primarily
      in the nucleus, excluding the nucleolus, although the expression of A2 protein
      was weaker than that of B1 protein. Staining pattern of these cells was similar
      to those observed in cancer cells. Western blotting with 4G8 and 2B2 demonstrated
      expression of A2 and B1 proteins in the airway cells. HnRNP A2/B1 proteins were
      apparently expressed in nonmalignant alveolar cells as well as cancer cells,
      although the expression in alveolar cells was weaker than that of cancer cells.
      More quantitative determination of A2/B1 is required to elucidate their
      significance in early lung cancer detection.

PMID- 14692564
TI  - Anthrax case timeline.

PMID- 14692563
TI  - Add-on effects of suplatast tosilate in bronchial asthma patients treated with
      inhaled corticosteroids.
AB  - Th2 cytokines play an important role in the pathogenesis of asthma. In the
      present study, we investigated the effect of suplatast tosilate, a selective Th2
      cytokine inhibitor, on asthma control, in terms of subjective symptoms and
      pulmonary function in patients treated with inhaled corticosteroids. Thirty-eight
      patients with bronchial asthma being treated with inhaled corticosteroids were
      given suplatast tosilate (100 mg three times daily) for 12 weeks, in a
      multicenter setting. During the study period, other medications were continued.
      Morning and evening peak expiratory flow, asthma symptoms, blood eosinophil count
      and serum IgE levels were monitored. Suplatast tosilate treatment was associated
      with a significant improvement in mean morning peak expiratory flow (from 295
      L/min to 348 L/min, P < 0.01) and evening peak expiratory flow (from 313 L/min to
      357 L/min, P < 0.01). The mean daily variation in peak expiratory flow was
      significantly reduced (from 11.6% to 7.3%, P < 0.01) by suplatast tosilate
      treatment. The greatest improvement in peak expiratory flow was observed in
      patients whose blood eosinophil counts were decreased by suplatast tosilate
      treatment. Treatment with suplatast tosilate improved pulmonary function in
      patients with bronchial asthma. Our results suggest the therapeutic effects
      observed may occur through suppression of eosinophilic inflammation.

PMID- 14692565
TI  - Best practices in public health risk and crisis communication.

PMID- 14692566
TI  - Electronic journal publishing in the age of bioterrorism: how fast is fast?

PMID- 14692567
TI  - Communication lessons learned in the Emergency Operations Center during CDC's
      anthrax response: a commentary.

PMID- 14692568
TI  - Communicating in times of uncertainty: the need for trust.

PMID- 14692569
TI  - The anthrax attacks in New York City: the "Giuliani press conference model" and
      other communication strategies that helped.

PMID- 14692570
TI  - Uncertain science and certain deadlines: CDC responses to the media during the
      anthrax attacks of 2001.
AB  - This paper presents a study in which communication personnel for the U.S. Centers
      for Disease Control and Prevention (CDC) provided first-hand accounts of the
      experience of responding to media inquiries during the 2001 anthrax attacks. In
      depth interviews were conducted with 19 communication professionals who worked
      either at the CDC headquarters in Atlanta or at field locations in the U.S. where
      persons were exposed to anthrax. The interviews sought CDC staff viewpoints on
      how the CDC handled a historically unprecedented level of press activity in terms
      of work locations and equipment, information flow and clearance, and staff roles.
      Staff reported that the situation led to new work practices, tools for performing
      the work, and an enhanced understanding of what it takes to be prepared for and
      to handle communication work during a terrorism-related health crisis. The paper
      provides a discussion of implications of the findings for CDC and for other
      public health organizations developing systems for communication response during
      health-related crises.

PMID- 14692571
TI  - Communication monitoring: shaping CDC's emergency risk communication efforts.
AB  - CDC develops and delivers health messages for a variety of audiences, including
      the public, health care professionals, public health researchers and
      practitioners, and policy makers. News media outlets--because of their broad
      reach and potential to influence knowledge, attitudes, and behaviors--are major
      channels for disseminating messages to these audiences. CDC has routinely
      monitored news outlets to identify message/information gaps and opportunities.
      The 9/11 terrorist attacks and the anthrax incidents that followed required CDC
      to transform its media monitoring system into a broader communication monitoring
      system, with both listening and telling functions, to support CDC's public health
      emergency response.

PMID- 14692572
TI  - Communicating anthrax in 2001: a comparison of CDC information and print media
      accounts.
AB  - Information about anthrax released by news media from October 4 to December 3,
      2001, was identified, sampled, coded, and compared with information released by
      CDC during that period using statistical analysis. In addition, communications
      about two anthrax-related issues were examined in depth. The quantitative
      analysis showed that, overall, CDC information releases and news coverage tracked
      fairly closely. When weight was defined as number of mentions, both sources gave
      the same weight to reports of risk for the population. The news sample gave
      roughly half the weight as CDC to who was exposed, how people were exposed, and
      what role antibiotics play in preventing anthrax. The samples were widely
      divergent (CDC high, news sample low) for public health precautions and other
      details. The in-depth, qualitative analysis showed that some reporters
      misinterpreted information provided by CDC, but they responded to requests to
      clarify the issue. The findings of this study suggest ways to improve future
      crisis communication efforts and demonstrate how differing methods of analysis
      can yield substantially different conclusions.

PMID- 14692573
TI  - Using opinion surveys to track the public's response to a bioterrorist attack.
AB  - To communicate effectively with the public during an emergency, health officials
      need to find out in real time what Americans know and believe, whom they trust,
      and what actions they are taking in response to the crisis. Short-duration
      surveys can provide vital information to guide public officials in their response
      to events and their communication efforts. Prior research has shown that such
      surveys, when statistically re-weighted, can offer timely results without
      unacceptable risk of bias. Using examples from public opinion surveys during the
      anthrax attacks of 2001, this article examines the role such surveys can play
      during a public health crisis.

PMID- 14692574
TI  - Public perceptions of information sources concerning bioterrorism before and
      after anthrax attacks: an analysis of national survey data.
AB  - This study examined data from six national surveys before and after the
      bioterrorist anthrax attacks in the fall of 2001. Public perceptions of
      information sources regarding bioterrorism were examined. The findings
      highlighted the importance of local television and radio and of cable and network
      news channels as information sources. The findings also showed the importance of
      national and local health officials as spokespersons in the event of bioterrorist
      incidents. Periodic surveys of public attitudes provide important, timely
      information for understanding audiences in communication planning.

PMID- 14692575
TI  - Leave no one behind: improving health and risk communication through attention to
      literacy.
AB  - Twice in recent times, the federal government mailed critical health-related
      information to every household in the United States. The mailings, the 1988
      brochure Understanding AIDS and the 2001 postcard A Message to Americans, were
      designed to provide the general public with important information about needed
      action. This paper compares the development process undertaken for each mailing.
      The authors assess content and format in light of communication principles and
      the functional literacy skills of average adults. The authors, noting that the
      reading grade level of the postcard exceeds the reading ability of the average
      adult, recommend that plain language guidelines be combined with health and risk
      communication principles in all future efforts to alert the public.

PMID- 14692576
TI  - Health literacy: essential for health communication.

PMID- 14692577
TI  - Elaborating a definition of health literacy: a commentary.

PMID- 14692578
TI  - Questions about hypotheticals and details in reporting on anthrax.

PMID- 14692579
TI  - Mass media, public health, and achieving health literacy.

PMID- 14692580
TI  - Surviving a public health crisis: tips for communicators.

PMID- 14692581
TI  - How the CDC is meeting the training demands of emergency risk communication.

PMID- 14692582
TI  - Optimistic bias and perceptions of bioterrorism in Michigan corporate
      spokespersons, fall 2001.
AB  - The notion that individuals believe that they are more likely than others to
      experience positive events and avoid negative ones is a well-documented
      phenomenon in the combined literatures of social psychology and health
      communication. The current study focuses on Michigan corporate spokespersons'
      perceptions of their company's risk and potential for optimistic bias. Beginning
      on September 10, 2001, and continuing through October 2001, telephone surveys
      were conducted by a professional survey research firm to assess spokespersons'
      awareness of and preparedness for a bioterrorism attack at their corporation, as
      well as to ascertain perceived self-risk relative to that of other, similar
      corporations. The results offer evidence of a robust optimistic bias, and provide
      an unusually timely snapshot of levels of corporate awareness of bioterrorism
      during a critical period of time in which the U.S. experienced its first anthrax
      attack.

PMID- 14692583
TI  - Communication during public health emergencies.

PMID- 14692584
TI  - Bioterrorism risk communication policy.

PMID- 14692585
TI  - Analysis of user-satisfaction with the use of a teleconsultation system in
      oncology.
AB  - There is an increasing interest in assessing telemedicine as alternative method
      of delivering high quality cancer treatment to patients living in rural areas. In
      the Province of Trento (north-east Italy) a tele-oncology system was implemented
      to provide non-surgical oncological consultation to district general hospitals.
      The aim of this study was to explore user-satisfaction with the system after 6
      months of experimentation. During the on-field validation two questionnaires with
      open and closed-response questions were distributed to 80 physicians and nurses 6
      months apart to investigate the users' expected benefits vs. perceived ones. The
      two questionnaires were compared to assess how perceived benefits differed from
      expected ones. Significant differences were found regarding improvements in: the
      standardization of diagnostic-therapeutic procedures using the Electronic Patient
      Record (EPR)]; information sharing; data updating; consultation speed; and the
      possibility to diminish patients' travels through the use of teleconsultation
      (TC). Physicians' responses showed a significant difference regarding the EPR's
      effects on relationship with patient, the nurses' responses with regards to its
      effects on care quality. Physicians felt that both modalities of teleconsultation
      were useful in enhancing communication with colleagues (86% for the synchronous
      TC, 80% for the asynchronous TC). Responses indicated that the major difficulties
      encountered were in the introduction of the system into the daily routine.
      Despite this, user expectations for its future use in clinical field were
      considerably high.

PMID- 14692586
TI  - Evaluating a spoken dialogue system for recording clinical observations during an
      endoscopic examination.
AB  - Paper, keyboard or mouse-driven systems may not be suitable for data capture
      because of the hands-busy constraint imposed by an endoscopic examination. A
      Spoken Dialogue System (SDS) has a number of advantages when compared to keyboard
      and mouse-driven input modalities, particularly with respect to hands free and
      eyes-free control of a system. However, any emerging technology will never
      deliver improved organizational effectiveness if it is not accepted and used. The
      Technology Acceptance Model (TAM) provides a framework that helps explain the
      determinants of computer acceptance. This study, through the application of TAM,
      demonstrates a high level of user acceptance with clinicians wanting to use
      spoken dialogue technology for recording clinical observations during an
      endoscopic examination. Clinicians would also prefer to use a SDS for recording
      endoscopy rather than use a paper-based or keyboard and mouse-driven system.
      Using a clinical narrative during an endoscopic examination was also perceived to
      be a natural way to record findings. Relationships between basic TAM variables
      were confirmed and relationships between quality of dialogue measures and TAM
      variables were established.

PMID- 14692587
TI  - Modular representation of the guideline text: an approach for maintaining and
      updating the content of medical education.
AB  - One of the principal challenges in the medical practice is the update of their
      knowledge. One of the prime roles of the Continuing Medical Education is to train
      the medical practitioners with the latest advances in health care, specialized to
      their needs. Online courses and classroom teaching with computer-based
      representations have become an established mode of delivering medical education.
      This paper deals with the modularized representation of a medical text concerning
      clinical practice guidelines. The proposed system takes into consideration the
      semantics of the Unified Medical Language System and is based upon the marking up
      and display of the knowledge using the XML and XSLT languages. This
      modularization of the concepts leads to the determination of the context of a
      portion or the whole document. Thus, after marking up using our system, the text
      components can be exchanged, modified or reconstructed, which, in turn, would
      help to maintain the updates in medical knowledge.

PMID- 14692588
TI  - A consumer health record for supporting the patient-centered management of
      chronic diseases.
AB  - OBJECTIVES: To design and implement a shareable consumer health record system to
      investigate whether the system can assist in the management of chronic diseases.
      METHODS: A toolkit was designed for constructing the consumer health record
      system in an evolutionary way. An ethnographic-like approach (formative
      evaluation) was used to let users (patients and care providers) assess the system
      leading to incremental changes in the system. RESULTS: The evaluation provided us
      with sufficient information about which parts of the system needed adaptation.
      The final consumer health record system was well accepted by patients and care
      providers. The system is Web-based and is used at home by patients having
      diabetes. Both care providers and patients enter data. The system can download
      the data from a glucose meter. It provides feedback to patients on the basis of
      entered data and incorporated guidelines. It also allows discussion forums.
      CONCLUSION: Formative evaluation is useful for obtaining feedback from users
      about prototype systems. Care providers and patients together worked with the
      consumer health record. Both parties appreciated the system. The approach
      described here can be used for developing systems for other chronic patient
      groups.

PMID- 14692589
TI  - A mathematical specification of the New Deal on junior doctors' hours.
AB  - OBJECTIVES: Our objective is to make the New Deal on junior doctors' hours
      sufficiently precise that the definitions may be used as a basis for computer
      software that checks the compliance of rotas or that automatically generates
      compliant rotas. METHODS: We formalize the clauses of the New Deal, as relevant
      to 'full shifts', using the Z specification language. RESULTS: The mathematical
      definitions are simple and concise. CONCLUSIONS: Mathematical specification is a
      useful way to express constraints on rotas unambiguously.

PMID- 14692590
TI  - An experimental environment for the production, exchange and discussion of fused
      radiology images, for the management of patients with residual brain tumour
      disease.
AB  - The present work aims to display the use of groupware as a tool for better
      management of the available resources (human, computing and imaging) within the
      University Hospital of Patras, Greece for the task of managing patients with
      postoperative residual brain tumour. Emphasis is given to the additional
      information that can be revealed and taken into account from novel image
      processing techniques, developed by our group, and the central role of the
      Medical Physicist in the groupware. Fused images, produced by the combination of
      CT, MR and SPECT representations of the brain, contain both anatomical and
      functional information and comprise a new representation of reality. Medical
      experts, unfamiliar with this new representation, form a groupware for the task
      of interpreting them and providing better services to the patient. Groupware
      procedures, facilitated by modern network technology, bring experts' tacit
      knowledge to the surface and facilitate its exchange.

PMID- 14692591
TI  - Scene setting: who is the voice of nutrition in Britain?
AB  - Currently the public is being inundated daily with information about diet and
      health, which is often conflicting and frequently not based on good quality
      evidence. This situation is fuelled by the ready access to information of
      variable quality via the internet, which has short circuited the previous checks
      and balances applied by researchers and the peer review process, whereby
      scientific findings were batted around and refined within the confines of the
      scientific research community, occasionally emerging to be incorporated into the
      advice given by health professionals. This situation, coupled with concern about
      the growing trend whereby detailed nutrition advice is sold to the public by self
      styled 'experts' with no formal degree-level training in the subject, prompted a
      conference that highlighted the importance of ensuring that nutrition advice is
      evidence-based, using a series of topical overviews. In recent years the
      Nutrition Society has played an active role in establishing mechanisms to assist
      the public in their search for high-quality dietary advice by badging individuals
      appropriately qualified to offer sound and relevant advice on nutrition.

PMID- 14692592
TI  - Improving communication to tackle obesity in the UK.
AB  - Obesity is a serious health issue. In the UK the prevalence of obesity has
      trebled in the last 20 years and today one in five adults is clinically obese.
      Research shows that obesity is a predictable response to an environment that
      favours the consumption of energy-dense foods and allows minimal physical
      activity. This finding implies that the efficacy of public health messages to
      individuals to inform their lifestyle choices will be enhanced by environmental
      changes that support and facilitate healthy options. The present paper focuses on
      the importance of communicating scientific knowledge to the stakeholders with a
      responsibility for tackling obesity and addresses some of the barriers that are
      encountered.

PMID- 14692593
TI  - Diet and cardiovascular disease in the UK: are the messages getting across?
AB  - Cardiovascular disease (CVD) is a leading cause of premature death in the UK and
      a major cause of ill health and disability. Whilst death rates from CVD have been
      falling since the late 1970s in the UK, levels of morbidity (such as angina) do
      not seem to be falling and may even be rising in some age-groups, especially as
      the population ages. There is broad consensus that lifestyle factors, including
      physical activity and diet, are fundamental determinants of heart disease risk.
      Current recommendations to reduce cardiovascular risk include maintaining a
      healthy body weight, eating five or more portions of fruit and vegetables each
      day, reducing intake of fat (particularly saturated fatty acids), reducing salt
      intake and eating one portion of oily fish per week. Although some improvements
      have been made in recent years (e.g. a reduction in total fat intake), national
      studies suggest that more effective campaigns are required to increase awareness
      of the benefits of these dietary changes. The present paper will discuss how the
      dietary messages relating to CVD are best communicated to the general public and
      will identify some of the main barriers to their implementation.

PMID- 14692594
TI  - Is there more to folates than neural-tube defects?
AB  - The purpose of the present paper is to review our current understanding of the
      chemistry and biochemistry of folic acid and related folates, and to discuss
      their impact on public health beyond that already established in relation to
      neural-tube defects. Our understanding of the fascinating world of folates and C1
      metabolism, and their role in health and disease, has come a long way since the
      discovery of the B-vitamin folic acid by Wills (1931), and its first isolation by
      Mitchell et al. (1941). However, there is still much to do in perfecting methods
      for the measurement of folate bioavailability, and status, with a high extent of
      precision and accuracy. Currently, examination of the relationships between
      common gene polymorphisms involved in C1 metabolism and folate bioavailability
      and folate status, morbidity, mortality and longevity is evaluated as a series of
      individual associations. However, in the future, examination of the concurrent
      effects of such common gene polymorphisms may be more beneficial.

PMID- 14692595
TI  - Plant polyphenols: are they the new magic bullet?
AB  - Epidemiological evidence suggests that diets rich in fruit and vegetables
      decrease the risk of premature mortality from major clinical conditions,
      including cancer and heart disease. However, it is not yet clear which components
      or combination of components in fruit and vegetables are protective and what is
      their mechanism of action. Such scientific uncertainty does not seem to inhibit
      the marketing of a huge range of plant-based concoctions, promoted as 'magic
      bullets' for optimum health. For example, the purported health-giving properties
      of plant polyphenols represent a case in which enthusiastic marketing claims may
      far exceed the current scientific evidence. Even when good experimental evidence
      exists, results need to be interpreted with caution in relation to human health
      benefits, as polyphenols may have limited bioavailability and may also be
      extensively metabolised. In addition, some polyphenols can be toxic and mutagenic
      in some cell culture systems. Until more is known about the activity and
      metabolic fate of polyphenols in the body, it would be better for the consumer to
      increase fruit and vegetable intake, and also to be wary of claims that these
      compounds are a panacea for good health.

PMID- 14692596
TI  - Nutrition and cancer prevention: diet-gene interactions.
AB  - Cancer is the major cause of death in the UK, and the Government has set a target
      to reduce death rate from cancer in individuals < 75 years by > or = 20% by 2010.
      Whilst earlier diagnosis and more effective treatments will contribute to meeting
      this target, there are considerable opportunities to prevent cancer by improving
      diet and other aspects of lifestyle. There is now a good understanding of the
      biological basis of carcinogenesis, which is providing the basis for mechanistic
      investigation of the chemo-preventive properties of certain foods and food
      components. It is becoming increasingly clear that there are important
      interactions between an individual's genotype (characterised by single nucleotide
      polymorphisms in particular genes) and habitual diet that modulate the risk of
      developing cancer. The technology to support this post-genomic revolution in
      nutrition research is now widely available, but brings with it considerable
      challenges in terms of study design and ethics. However, in the absence of a
      robust body of evidence on which dietary strategies will benefit which
      individuals, soundly based genetically-targeted nutrition advice to the public on
      cancer prevention is a little way in the future.

PMID- 14692598
TI  - Physical activity and resting metabolic rate.
AB  - The direct effects of physical activity interventions on energy expenditure are
      relatively small when placed in the context of total daily energy demands. Hence,
      the suggestion has been made that exercise produces energetic benefits in other
      components of the daily energy budget, thus generating a net effect on energy
      balance much greater than the direct energy cost of the exercise alone. Resting
      metabolic rate (RMR) is the largest component of the daily energy budget in most
      human societies and, therefore, any increases in RMR in response to exercise
      interventions are potentially of great importance. Animal studies have generally
      shown that single exercise events and longer-term training produce increases in
      RMR. This effect is observed in longer-term interventions despite parallel
      decreases in body mass and fat mass. Flight is an exception, as both single
      flights and long-term flight training induce reductions in RMR. Studies in
      animals that measure the effect of voluntary exercise regimens on RMR are less
      commonly performed and do not show the same response as that to forced exercise.
      In particular, they indicate that exercise does not induce elevations in RMR.
      Many studies of human subjects indicate a short-term elevation in RMR in response
      to single exercise events (generally termed the excess post-exercise O2
      consumption; EPOC). This EPOC appears to have two phases, one lasting < 2 h and a
      smaller much more prolonged effect lasting up to 48 h. Many studies have shown
      that long-term training increases RMR, but many other studies have failed to find
      such effects. Data concerning long-term effects of training are potentially
      confounded by some studies not leaving sufficient time after the last exercise
      bout for the termination of the long-term EPOC. Long-term effects of training
      include increases in RMR due to increases in lean muscle mass. Extreme
      interventions, however, may induce reductions in RMR, in spite of the increased
      lean tissue mass, similar to the changes observed in animals in response to
      flight.

PMID- 14692599
TI  - Uncoupling protein 3 and physical activity: the role of uncoupling protein 3 in
      energy metabolism revisited.
AB  - Physical activity influences energy metabolism in human subjects by increasing
      activity-induced energy expenditure and resting metabolic rate for several hours
      after exercise. On the other hand, physical activity increases mechanical energy
      efficiency, suggesting that trained subjects would need less energy for daily
      activities. The underlying mechanism by which physical activity influences energy
      metabolism is largely unknown. The skeletal muscle-specific homologue of
      uncoupling protein (UCP) 1, UCP3, could possibly play a major role in energy
      expenditure. UCP3 is, like UCP1, able to uncouple respiration from ATP
      production. A strong link or association between the UCP3 gene and energy
      metabolism was found. Furthermore, UCP3 mRNA expression is related to sleeping
      metabolic rate, and thyroid hormone, a powerful stimulator of energy expenditure,
      up regulates UCP3. Finally, mice overexpressing UCP3 are hyperphagic but lean.
      These findings indicated that UCP3 is related to energy metabolism and that UCP3
      could have a role in the effect of physical activity on energy expenditure. Thus,
      acute exercise up regulates UCP3, whereas endurance training results in the down
      regulation of UCP3 protein content. Only a minimal amount of physical activity is
      needed for down-regulation of UCP3. Moreover, there is very strong evidence that
      UCP3 is negatively related to mechanical energy efficiency, suggesting that the
      down-regulation of UCP3 with training increases mechanical energy efficiency.
      Taken together, although the exact function of UCP3 is still unknown, exercise
      and training studies clearly show that under certain circumstances UCP3 is
      strongly related to human energy metabolism, possibly as a secondary effect of
      its (yet) unknown primary function.

PMID- 14692597
TI  - Physical activity interventions in the prevention and treatment of paediatric
      obesity: systematic review and critical appraisal.
AB  - Interventions for prevention and treatment of childhood obesity typically target
      increases in physical activity and, more recently, reductions in physical
      inactivity (sedentary behaviour such as television viewing). However, the
      evidence base for such strategies is extremely limited. The main aim of the
      present review was to update the systematic review and critical appraisal of
      evidence in the light of the recent rapid expansion of research in this area.
      Randomised controlled trials (RCT) that targeted activity or inactivity, that
      followed up children or adolescents for at least 1 year and that included an
      objective weight-related outcome measure were included. Trials were appraised
      using previously published criteria (Harbour & Miller, 2001), and literature
      search strategies described previously (Reilly et al. 2002) were updated to May
      2002. A total of four new RCT, two new systematic reviews and one meta-analysis
      were identified. The evidence base has increased markedly since the completion of
      earlier reviews, although high-quality evidence is still lacking. The evidence on
      childhood obesity prevention is not encouraging, although promising targets for
      prevention are now clear, notably reduction in sedentary behaviour. There is
      stronger evidence that targeting activity and/or inactivity might be effective in
      paediatric obesity treatment, but doubts as to the generalisability of existing
      interventions, and the clinical relevance of the interventions is unclear.
      Further research in settings outside the USA is urgently needed, and two ongoing
      RCT in Scotland are summarised.

PMID- 14692600
TI  - Impacts of vigorous and non-vigorous activity on daily energy expenditure.
AB  - Activity intensity is a potential determinant of activity-induced energy
      expenditure. Tri-axial accelerometery is the most objective measurement technique
      for the assessment of activity intensity, in combination with doubly-labelled
      water for the measurement of energy expenditure under free-living conditions.
      Data on the effects of subject characteristics, including body size and age, and
      exercise training on the relationship between activity intensity and daily energy
      expenditure are reviewed. Average daily metabolic rate and non-basal energy
      expenditure are positively related to body size. The duration and intensity of
      physical activities do not need to be equivalent to the energy spent on activity.
      Obese subjects spend more energy on physical activity but can perform fewer
      activities, especially high-intensity (weight-bearing) activities, because of
      their higher body weight. Physical activity generally declines gradually from
      about 60 years of age onwards. Most subjects > 80 years have an activity level
      well below the level defined for sedentary middle-aged adults. Spending
      relatively more time on low-intensity activities has a negative effect on the
      mean physical activity level. To obtain a higher physical activity level does not
      necessarily imply high-intensity activities. In an average subject 25% of the
      activity-induced energy expenditure may be attributed to high-intensity
      activities. Exercise training, as a form of high-intensity activity, affects the
      physical activity level more in younger subjects than in elderly subjects.

PMID- 14692601
TI  - Cross talk between physical activity and appetite control: does physical activity
      stimulate appetite?
AB  - Physical activity has the potential to modulate appetite control by improving the
      sensitivity of the physiological satiety signalling system, by adjusting
      macronutrient preferences or food choices and by altering the hedonic response to
      food. There is evidence for all these actions. Concerning the impact of physical
      activity on energy balance, there exists a belief that physical activity drives
      up hunger and increases food intake, thereby rendering it futile as a method of
      weight control. There is, however, no evidence for such an immediate or automatic
      effect. Short (1-2 d)-term and medium (7-16 d)-term studies demonstrate that men
      and women can tolerate substantial negative energy balances of < or = 4 MJ energy
      cost/d when performing physical activity programmes. Consequently, the immediate
      effect of taking up exercise is weight loss (although this outcome is sometimes
      difficult to assess due to changes in body composition or fluid
      compartmentalization). However, subsequently food intake begins to increase in
      order to provide compensation for about 30% of the energy expended in activity.
      This compensation (up to 16 d) is partial and incomplete. Moreover, subjects
      separate into compensators and non-compensators. The exact nature of these
      differences in compensation and whether it is actually reflective of non
      compliance with protocols is yet to be determined. Some subjects (men and women)
      performing activity with a cost of < or = 4 MJ/d for 14 d, show no change in
      daily energy intake. Conversely, it can be demonstrated that when active
      individuals are forced into a sedentary routine food intake does not decrease to
      a lower level to match the reduced energy expenditure. Consequently, this
      situation creates a substantial positive energy balance accompanied by weight
      gain. The next stage is to further characterize the compensators and non
      compensators, and to identify the mechanisms (physiological or behavioural) that
      are responsible for the rate of compensation and its limits.

PMID- 14692602
TI  - Energy expenditure, physical activity and body-weight control.
AB  - Regular physical exercise and endurance training are associated with low body
      weight and low body fat mass. The relationship between exercise and body-weight
      control is complex and incompletely understood. Regular exercise may decrease
      energy balance through an increase in energy expenditure or an increase in fat
      oxidation. It may also contribute to weight loss by modulating nutrient intake.
      An intriguing question that remains unresolved is whether changes in nutrient
      intake or body composition secondarily affect spontaneous physical activity. If
      this were the case, physical activity would represent a major adaptative
      mechanism for body-weight control.

PMID- 14692603
TI  - Non-exercise activity thermogenesis.
AB  - Non-exercise activity thermogenesis (NEAT) is the energy expended that is not
      from sleeping, eating or sports-like exercise. It ranges from the energy expended
      walking to work, typing, performing yard work, undertaking agricultural tasks and
      fidgeting. NEAT can be measured by one of two approaches. The first approach is
      to measure or estimate total NEAT. Here, total daily energy expenditure is
      measured and from it is subtracted BMR + thermic effect of food. The second is
      the factoral approach whereby the components of NEAT are quantified and total
      NEAT calculated by summing these components. The amount of NEAT that human
      subjects perform represents the product of the amount and types of physical
      activities and the thermogenic cost of each activity. The factors that affect the
      NEAT of a human subject are readily divisible into biological factors, such as
      weight, gender and body composition, and environmental factors, such as
      occupation or dwelling within a 'concrete jungle'. The combined impact of these
      factors explains the substantial variance in human NEAT. The variability in NEAT
      might be viewed as random but human data contradict this perception. It appears
      that changes in NEAT subtly accompany experimentally-induced changes in energy
      balance and are important in the physiology of weight change. NEAT and
      sedentariness may thus be important in obesity. It then becomes intriguing to
      dissect mechanistic studies that delineate how NEAT is regulated by neural,
      peripheral and humoral factors. NEAT may be a carefully-regulated 'tank' of
      physical activity that is crucial for weight control.

PMID- 14692604
TI  - How active are we? Levels of routine physical activity in children and adults.
AB  - The accurate measurement of physical activity is fraught with problems in adults,
      but more especially in children because they have more complex and multi
      dimensional activity patterns. In addition, the results of different studies are
      often difficult to interpret and compare, because of the diversity of
      methodological approaches, differences in data analysis and reporting, and the
      adoption of varying definitions of what constitutes an appropriate level of
      activity. Furthermore, inactivity is seldom quantified directly. Although there
      exists an extensive literature documenting the health benefits of regular
      physical activity in adults, activity-health relationships in children are not
      clear-cut. Current recommendations reinforce the concept of health-related
      activity, accumulating 30 min moderate-intensity exercise on at least 5 d/week
      (adults) and 1 h moderate-intensity exercise/d (children). Evidence suggests a
      high prevalence of inactivity in adults, but whether or not inactivity is
      increasing cannot be assessed currently. Similarly, no definite conclusions are
      justified about either the levels of physical activity of children, or whether
      these are sufficient to maintain and promote health. Data to support the belief
      that activity levels in childhood track into adulthood are weak. Inactivity is
      associated with an increased risk of weight gain and obesity, but causality
      remains to be established. In children there is strong evidence to demonstrate a
      dose response relationship between the prevalence and incidence of obesity and
      time spent viewing television. Future research should focus on refining
      methodology for physical activity assessment to make it more sensitive to the
      different dimensions and contexts of activity in different age-groups.

PMID- 14692605
TI  - The medical management of intestinal failure: methods to reduce the severity.
AB  - A new definition of intestinal failure is of reduced intestinal absorption so
      that macronutrient and/or water and electrolyte supplements are needed to
      maintain health or growth. Severe intestinal failure is when parenteral nutrition
      and/or fluid are needed and mild intestinal failure is when oral supplements or
      dietary modification suffice. Treatment aims to reduce the severity of intestinal
      failure. In the peri-operative period avoiding the administration of excessive
      amounts of intravenous saline (9 g NaCl/l) may prevent a prolonged ileus.
      Patients with intermittent bowel obstruction may be managed with a liquid or low
      residue diet. Patients with a distal bowel enterocutaneous fistula may be managed
      with an enteral feed absorbed by the proximal small bowel while no oral intake
      may be needed for a proximal bowel enterocutaneous fistula. Patients undergoing
      high-dose chemotherapy can usually tolerate jejunal feeding. Rotating antibiotic
      courses may reduce small bowel bacterial overgrowth in patients with chronic
      intestinal pseudoobstruction. Restricting oral hypotonic fluids, sipping a
      glucose-saline solution (Na concentration of 90-120 mmol/l) and taking anti
      diarrhoeal or anti-secretory drugs, reduces the high output from a jejunostomy.
      This treatment allows most patients with a jejunostomy and > 1 m functioning
      jejunum remaining to manage without parenteral support. Patients with a short
      bowel and a colon should consume a diet high in polysaccharides, as these
      compounds are fermented in the colon, and low in oxalate, as 25% of the oxalate
      will develop as calcium oxalate renal stones. Growth factors normally produced by
      the colon (e.g. glucagon-like peptide-2) to induce structural jejunal adaptation
      have been given in high doses to patients with a jejunostomy and do marginally
      increase the daily energy absorption.

PMID- 14692606
TI  - Surgical management of intestinal failure.
AB  - Surgery plays a key role in the management of both acute and, less frequently,
      chronic intestinal failure. Acute intestinal failure frequently requires surgical
      treatment when it arises as a consequence of intestinal fistulation or
      obstruction. In specialised clinical practice approximately 50% of acute
      intestinal failure is associated with intestinal fistulas and in approximately
      50% of patients, this condition arises as part of the natural history or
      complicating treatment for Crohn's disease. A considerable proportion of such
      patients have abdominal infection and present complex nutritional and metabolic
      problems. The most important aspect of the surgical management of patients with
      acute intestinal failure associated with intra-abdominal infection is management
      of sepsis, since recovery is unlikely in the presence of active infection.
      Moreover, effective nutritional support and restoration of body composition is
      not possible if sepsis remains unresolved. Surgical strategies to deal with intra
      abdominal infection may involve percutaneous drainage, laparotomy and resection
      of fistulating segments of intestine and, when infection is persistent and
      contamination extensive, laparostomy (a technique in which the abdomen is left
      open and allowed to heal by secondary intention). Surgical treatment should not
      only be timely and effective, but also aimed at preventing secondary damage to
      the small intestine, in order to minimise the risk of short bowel syndrome. In
      some cases a proximal defunctioning stoma may be required, with prolonged
      nutritional support, using either home total parenteral nutrition or feeding via
      the defunctioned distal gut (fistuloclysis), pending restoration of intestinal
      continuity. The role of surgical treatment for patients with short bowel syndrome
      is less clear. While surgery is frequently required for the management of
      complications of short bowel syndrome (including gallstones and possibly peptic
      ulcer disease), the role of intestinal lengthening and tapering procedures (to
      increase functional intestinal length), and artificial valves, reversed segments
      and colonic interposition (to reduce intestinal transit) remains controversial.
      For some patients with short bowel syndrome and, in particular, those with
      combined intestinal and hepatic failure, intestinal transplantation may become
      the treatment of choice as long-term results continue to improve.

PMID- 14692607
TI  - Recent developments in the delivery of home parenteral nutrition in the UK.
AB  - The British Artificial Nutrition Survey 2001 recorded 507 home parenteral
      nutrition (HPN) patients (Crohn's disease 31.5%, vascular disease 19.7%, cancer
      6.9%). Parenteral nutrition was administered via tunnelled central line (92%) and
      supplied by a commercial homecare company in 89% of cases. The majority of HPN
      patients live at home (95.5%) with an independent life (74%), normal activity
      (59.2%) and 92% survive 1 year. However, there is good evidence that the
      geographical distribution of HPN patients is uneven (prevalence no patients to
      thirty-six patients per million of the population) suggesting inequity of access.
      Patients are increasingly concerned about the distances travelled to main centres
      and variable standards of more local support. Funding issues continue to cause
      difficulties as commissioning of health care transfers from Health Authorities to
      Primary Care Trusts. The two nationally-funded intestinal failure units provide
      HPN services to 220 HPN patients. HPN-related readmissions have displaced those
      awaiting admission for intestinal failure treatment, for which the waiting list
      mortality in one unit has risen to 14%. The government has now recognised HPN as
      a specialised service distinct from intestinal failure and that existing medium
      sized HPN units should be encouraged to take on HPN patients from intestinal
      failure units and smaller units. In Scotland a Managed Clinical HPN Network
      supported by the Scottish administration now cares for seventy-two patients under
      common protocols. The challenge for the future is how to provide high-quality
      care to all who need it in the rest of the UK.

PMID- 14692609
TI  - Tissue engineering of the gastrointestinal tract for surgical replacement: a
      nutrition tool of the future?
AB  - Optimal nutrition depends on the multiple complex functions performed by the
      gastrointestinal tract, which range from basic functions such as storage, conduit
      and mechanical processing to more finely regulated capabilities such as vectorial
      transport, immune defence and cell signalling. Surgical strategies to supply
      lacking gastrointestinal tract tissues have relied on either replacement by proxy
      (surgical substitution) or the introduction of prostheses. Tissue engineering
      seeks to replace missing tissues with engineered tissues that more accurately
      reproduce the native physiological and anatomical milieu. It is now possible to
      engineer several areas of the gastrointestinal tract with high fidelity, and to
      employ tissue-engineered bowel in replacement in animal models. These replacement
      models have reflected excellent anatomical and physiological recapitulation of
      native bowel by the tissue-engineered constructs in vivo.

PMID- 14692608
TI  - Gut failure and abdominal visceral transplantation.
AB  - Despite the reported high survival with total parenteral nutrition (TPN) therapy
      for patients with intestinal failure, a considerable number of patients do not
      escape the potential risks of TPN-associated complications, including hepatic
      failure, vanishing of central venous access and line sepsis. Thus, intestinal,
      liver-intestinal and multivisceral transplantation have recently emerged to
      rescue those who can no longer be maintained on TPN. Before this development, and
      for nearly three decades, small-bowel transplantation was plagued with
      uncontrolled rejection, graft v. host disease and fatal infection. These barriers
      stemmed from the large gut lymphoid mass and heavy microbial load contained in
      the intestinal lumen. The recent improvement in survival after the clinical
      introduction of tacrolimus with achievement of full enteric nutritional autonomy
      qualified the procedure by the US Health Care Financing Administration as the
      standard of care for patients with intestinal and TPN failure. The decision was
      supported by a decade of clinical experience with cumulative improvement in
      patient and graft survival. In addition, the introduction of new effective
      immunoprophylactic agents and novel therapeutic approaches has contributed to a
      further increase in the therapeutic advantages of the procedure. The present
      review article outlines the current clinical practice of intestinal
      transplantation and defines new management strategies with the aim of raising the
      level of the procedure to be a better alternative therapy for TPN-dependent
      patients.

PMID- 14692610
TI  - Impaired energy metabolism during neonatal sepsis: the effects of glutamine.
AB  - Neonatal sepsis is an important cause of morbidity and mortality as a result of
      multiple organ system failure, particularly in neonates requiring total
      parenteral nutrition. Suitable therapies and support are needed both to prevent
      sepsis and to prevent multiple organ failure. After bacterial infection, pro
      inflammatory cytokines trigger the antimicrobial activity of macrophages and
      neutrophils, resulting in production of reactive species such as H2O2, NO,
      superoxide and peroxynitrite. However, excess production can lead to host tissue
      damage. Incubation of either hepatocytes or heart mitochondria from neonatal rats
      with these reactive species, or with cytokines, leads to impairment of
      mitochondrial oxidative function, and in an animal model of neonatal sepsis
      similar results to the in vitro findings have been demonstrated. Recent in vivo
      studies, using indirect calorimetry of suckling rat pups, show that during
      endotoxaemia there is a profound hypometabolism, associated with hypothermia.
      Having determined that cellular oxidative function may be impaired during sepsis,
      it is of great importance to try to identify therapeutic measures. Much interest
      has been shown in glutamine, which may become essential during sepsis. It has
      been shown that hepatic glutamine is rapidly depleted during endotoxaemia. When
      hepatocytes from endotoxaemic rats were incubated with glutamine, there was a
      restoration of mitochondrial structure and metabolism. In vivo, intraperitoneal
      injection of glutamine into endotoxic suckling rats partially reversed
      hypometabolism, markedly reduced the incidence of hypothermia and improved
      clinical status. These results suggest that glutamine has a beneficial effect
      during sepsis in neonates.

PMID- 14692611
TI  - Fatty acid metabolism in obesity and type 2 diabetes mellitus.
AB  - Disturbances in pathways of lipolysis and fatty acid handling are of importance
      in the aetiology of obesity and type 2 diabetes mellitus. There is evidence that
      a lowered catecholamine-mediated lipolytic response may play a role in the
      development and maintenance of increased adipose tissue stores. Increased adipose
      tissue stores, a disturbed insulin-mediated regulation of lipolysis and subnormal
      skeletal muscle non-esterified fatty acid (NEFA) uptake under conditions of high
      lipolytic rate may increase circulating NEFA concentrations, which may promote
      insulin resistance and cardiovascular complications. In addition, a disturbance
      of NEFA uptake by adipose tissue postprandially is also a critical determinant of
      plasma NEFA concentration. Furthermore, evidence is increasing that insulin
      resistant muscle is characterised by a lowered ability to oxidise fatty acids. A
      dysbalance between fatty acid uptake and fatty acid oxidation may in turn be a
      factor promoting accumulation of lipid intermediates and triacylglycerols within
      skeletal muscle, which is strongly associated with skeletal muscle insulin
      resistance. The present review describes the reported disturbances in pathways of
      lipolysis and skeletal muscle fatty acid handling, and discusses underlying
      mechanisms and metabolic consequences of these disturbances.

PMID- 14692612
TI  - Home enteral-tube feeding: the changing role of the dietitian.
AB  - Enteral feeding in primary care has increased markedly over the last decade. It
      allows patients to be discharged to home or residential care who previously would
      have remained in hospital. Difficulties do arise for patients, their carers and
      health professionals, as care of these patients and support for health
      professionals is often patchy or non-existent. Dietitians are uniquely placed to
      participate in the management of tube feeding in primary care, provide support
      and education to patients and their carers, evaluate treatment and promote better
      outcomes for patients receiving tube feeding.

PMID- 14692613
TI  - An alternative perspective: a critical evaluation of the Waddell threshold
      extrapolation model in chemical carcinogenesis.
AB  - In a recent Perspective article (Toxicologic Pathology 31: 260-262, 2003) Waddell
      asserts that he has developed a log linear extrapolation model that can
      demonstrate a threshold and resolve for once and for all the uncertainies
      associated with low dose cancer risk extrapolation. However, his method
      essentially forces, rather than demonstrates, a threshold, and has many serious
      flaws that result in significant under-estimation of low dose risk. It would be a
      serious mistake for the scientific community to adopt Waddell's log linear
      extrapolation model for chemical carcinogenesis risk assessment.

PMID- 14692614
TI  - Toxicogenomics in drug development.
AB  - Toxicogenomics represents the merging of toxicology with technologies that have
      been developed, together with bioinformatics, to identify and quantify global
      gene expression changes. It represents a new paradigm in drug development and
      risk assessment, which promises to generate a wealth of information towards an
      increased understanding of the molecular mechanisms that lead to drug toxicity
      and efficacy, and of DNA polymorphisms responsible for individual susceptibility
      to toxicity. Gene expression profiling, through the use of DNA microarray and
      proteomic technologies will aid in establishing links between expression
      profiles, mode of action and traditional toxic endpoints. Such patterns of gene
      expression, or 'molecular fingerprints' could be used as diagnostic or predictive
      markers of exposure, that is characteristic of a specific mechanism of induction
      of that toxic or efficacious effect. It is anticipated that toxicogenomics will
      be increasingly integrated into all phases of the drug development process
      particularly in mechanistic and predictive toxicology, and biomarker discovery.
      This review provides an overview of the expression profiling technologies applied
      in toxicogenomics. and discusses the promises as well as the future challenges of
      applying this discipline to the drug development process.

PMID- 14692615
TI  - Histopathological study on the PTHrP-induced incisor lesions in rats.
AB  - Parathyroid hormone related peptide (PTHrP) was discovered as a causative factor
      of humoral hypercalcemia of malignancy (HHM). The present study elucidates the
      histopathological characters of incisor lesions in the HHM rat model. Nude rats
      were implanted with PTHrP-expressing tumor (LC-6) cells, maintained for 12 weeks,
      after which the mandibular incisors were collected. Incisor fractures were
      observed grossly. Microscopically, hypercalcified dentin, dentin niche with
      osteodentin, and thinning of dentin were observed. Hypercalcified dentin was
      observed as a basophilic line of calcified dentin without associated
      odontoblastic changes, whereas dentin niche and thinning of dentin occurred with
      osteodentin and loss of cell height, respectively. In contrast with
      hypercalcified dentin, which was distributed throughout the dentin, dentin niche
      and thinning of dentin were localized to the labial area of the apical and middle
      region, and to the labial and lingual areas of the middle and incisal region,
      respectively. These results suggest that hypercalcemia affected the entire
      calcification process resulting in hypercalcified dentin, and that high PTHrP
      concentrations affected selective populations of odontoblasts resulting in
      formation of dentin niche and thinning of dentin. The localization of dentin
      niche and thinning of dentin also suggest that PTHrP may also be involved
      odontoblastic development in the rat.

PMID- 14692616
TI  - Spontaneous acute tumor lysis syndrome in a DBA/1J mouse: a case report and
      review.
AB  - Spontaneous acute tumor lysis syndrome (ATLS) was diagnosed in a 10-month-old
      female DBA/1J sentinel mouse with leukemic lymphoma. The mouse was unable to
      maintain balance and died shortly after being observed rolling around in its
      cage. Disseminated neoplastic disease, including a large cranial mediastinal
      mass, enlarged lymph nodes and splenomegaly, was present at necropsy.
      Histopathologic examination revealed widespread massive necrosis of lymphoblastic
      tumor cells, and widely disseminated microemboli composed of nuclear and
      cytoplasmic cell debris. Although ATLS is widely recognized as an oncologic
      emergency in humans, acute lesions of ATLS have not been described. The
      mechanical obstruction of capillary beds by microemboli originating from
      disintegrating necrotic tumor cells was the likely cause of clinical signs and
      death in this mouse. We propose that similar microemboli may contribute to the
      pathogenesis of the acute renal failure and other clinical signs associated with
      ATLS in humans. Recognition of spontaneous ATLS in laboratory animals is
      especially important in studies that assess the efficacy and/or toxicity of
      anticancer treatments, where early deaths due to ATLS might mistakenly be
      attributed to a direct test article effect.

PMID- 14692617
TI  - Mutation and overexpression of the transgene in ethylnitrosourea-induced tumors
      in mice carrying a human prototype c-Ha-ras gene.
AB  - To investigate mechanisms underlying accelerated carcinogenesis in mice carrying
      a human prototype c-Ha-ras gene (rasH2 mouse), mutations and the expression
      profile of the transgene were evaluated in 14 tumors induced by a single
      injection of ethylnitrosourea (ENU), with or without additional beta-estradiol 3
      benzoate (EB) treatment. Although no codon 12 mutations were detected, changes in
      codon 61 were evident in all lung adenocarcinomas, skin squamous cell carcinomas
      and forestomach squamous cell carcinomas examined. The mRNA levels of the
      transgene in these lesions were also elevated 1.71- to 4.77-fold, 3.04- to 5.18
      fold, and 3.00- to 5.67-fold, respectively, in comparison with those in the
      normal livers of rasH2 mice. The results obtained in this study suggest that
      mutations in codon 61 and amplification of the transgene play key roles in the
      carcinogenesis induced by ENU in rasH2 mice.

PMID- 14692618
TI  - Inhibition by ethinylestradiol of N-ethyl-N-nitrosourea-initiated uterine
      carcinogenesis in transgenic mice carrying a human prototype C-Ha-ras gene (rasH2
      mice).
AB  - In order to demonstrate the tumor promoting effect of ethinylestradiol (EE) in
      our uterine carcinogenesis model, rasH2 or ICR mice given an intraperitoneal
      injection of 120 mg/kg body weight of N-ethyl-N-nitrosourea (ENU) or an intra
      uterine injection of 50 mg/kg body weight of ENU, respectively, followed by 2.5
      or 0 ppm EE in the diet for 24 weeks in experiment 1 and 6 weeks in experiment 2.
      In experiment 1, in ICR mice, the incidences of adenocarcinomas in the ENU alone
      and the ENU+EE groups were 0% and 37.5%, respectively, the difference being
      statistically significant. The incidences of atypical hyperplasias and
      endometrial hyperplasias in the ENU+EE group were also significantly higher than
      those in the ENU alone group. In rasH2 mice, on the other hand, no endometrial
      proliferative lesions were induced in the uterus of the ENU+EE group, although
      uterine adenocarcinomas (55.6%), atypical hyperplasias (33.3%), and endometrial
      hyperplasias (22.2%) were observed in the ENU alone group. Proliferating cell
      nuclear antigen (PCNA) positive indices for uterine adenocarcinomas and atypical
      hyperplasias in ICR mice treated with ENU+EE showed high values, but those in
      rasH2 mice given ENU alone were comparable to data for intact epithelium. In
      experiment 2, the immunohistochemical expression of estrogen receptor alpha (ER
      alpha) in the uterine luminal and glandular epithelium in the ENU+EE group of ICR
      mice was moderate to marked, but that in the ENU alone group was slight. There
      was no consistent difference in ER alpha expression in the uterine luminal and
      glandular epithelium between ENU+EE and ENU alone groups of rasH2 mice. These
      results suggest that 2.5 ppm EE paradoxically inhibits the uterine carcinogenesis
      in rasH2 mice initiated with ENU.

PMID- 14692619
TI  - Differences in immunohistochemical expression of xenobiotic-metabolizing enzymes
      between normal pancreas, chronic pancreatitis and pancreatic cancer.
AB  - Metabolic activation of many toxins, carcinogens, drugs, and anti-cancer agents
      is governed by the cytochrome P450 (CYP) drug-metabolizing enzyme system. To help
      elucidate the role of this enzyme system in the pathogenesis of chronic
      inflammatory and malignant pancreatic diseases, we compared the
      immunohistochemical expression pattern of 8 CYP-enzymes in 24 normal, 20 chronic
      pancreatitis, and 21 pancreatic cancer specimens using antibodies to CYP 1A1,
      1A2, 2B6, 2C8/9/19, 2D6, 2E1, and 3A4, and the NADPH cytochrome P450 oxido
      reductase (NA-OR). Compared to the normal pancreas, a higher frequency of
      immunopositivity for CYP 1A2, 2B6, 2C8/9/19, 2D6, and NA-OR was found in chronic
      pancreatitis, and of all CYPs but 1A2 in pancreatic cancer. On the other hand,
      CYP 1A1 and 2E1 antibody staining was less frequently observed in chronic
      pancreatitis. In all specimens with pancreatic polypeptide (PP)-rich regions
      (pancreas head), more islet cells than ductal and acinar cells were
      immunopositive. Moreover, the immunoreactivity of islet cells from PP-rich
      specimens with anti-CYP antibodies was consistently more frequent and intense
      than in islet cells from PP-poor areas (body and tail). Immunoreactivity for
      xenobiotic-metabolizing enzymes was frequently observed in the normal pancreas,
      chronic pancreatitis, and pancreatic cancer, and displayed differences of its
      frequency and intensity between the 3 groups. Considering immunohistochemical
      evidence of enzyme expression and pancreatic blood supply together, islet cells
      appear to be an important and possible early site of CYP-enzyme induction in
      pancreatic diseases.

PMID- 14692620
TI  - The expression and significance of metallothioneins in murine organs and tissues
      following mercury vapour exposure.
AB  - The fate of inspired mercury vapour (Hg0) is critical in the central nervous
      system (CNS) where it can circumvent the blood-brain barrier (BBB) at the
      neuromuscular junction (NMJ) and accumulate indefinitely in motor neurons by
      retrograde transport. The detoxification of systemic Hg0 by lung and liver
      requires investigation. We exposed 129/Sv wild-type (Wt) and 129/Sv MT-I, II
      double knockout (KO) mice to 500 microg Hg0/m3 for 4 hours to investigate the
      expression of MT in the lung, liver, and spinal cord following Hg0 exposure using
      unexposed groups as controls. There were congestive changes in liver and lung of
      both Wt and MT-KO groups of Hg0-treated mice; these changes appeared more
      pronounced in the MT-KO group. Motor neurons in the spinal cord did not show any
      pathological changes. Based on expression of MT, liver appears to have a major
      role in trapping and stabilising mercury. In the spinal cord, MT was expressed in
      all white matter astrocytes and in some grey matter astrocytes. Notably, motor
      neurons did not express MT, and the presence of MT could not be demonstrated in
      the axons of the ventral root. The absence of MT expression in motor neurons and
      their axons suggests the dependence of the motor system on the detoxifying
      capacity of liver MTs.

PMID- 14692621
TI  - DNA damage in nasal and brain tissues of canines exposed to air pollutants is
      associated with evidence of chronic brain inflammation and neurodegeneration.
AB  - Acute, subchronic, or chronic exposures to particulate matter (PM) and pollutant
      gases affect people in urban areas and those exposed to fires, disasters, and
      wars. Respiratory tract inflammation, production of mediators of inflammation
      capable of reaching the brain, systemic circulation of PM, and disruption of the
      nasal respiratory and olfactory barriers are likely in these populations. DNA
      damage is crucial in aging and in age-associated diseases such as Alzheimer's
      disease. We evaluated apurinic/apyrimidinic (AP) sites in nasal and brain genomic
      DNA, and explored by immunohistochemistry the expression of nuclear factor
      NFkappaB p65, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX2),
      metallothionein I and II, apolipoprotein E, amyloid precursor protein (APP), and
      beta-amyloid(1-42) in healthy dogs naturally exposed to urban pollution in Mexico
      City. Nickel (Ni) and vanadium (V) were measured by inductively coupled plasma
      mass spectrometry (ICP-MS). Forty mongrel dogs, ages 7 days-10 years were studied
      (14 controls from Tlaxcala and 26 exposed to urban pollution in South West
      Metropolitan Mexico City (SWMMC)). Nasal respiratory and olfactory epithelium
      were found to be early pollutant targets. Olfactory bulb and hippocampal AP sites
      were significantly higher in exposed than in control age matched animals. Ni and
      V were present in a gradient from olfactory mucosa > olfactory bulb > frontal
      cortex. Exposed dogs had (a) nuclear neuronal NFkappaB p65, (b) endothelial,
      glial and neuronal iNOS, (c) endothelial and glial COX2, (d) ApoE in neuronal,
      glial and vascular cells, and (e) APP and beta amyloid(1-42) in neurons, diffuse
      plaques (the earliest at age 11 months), and in subarachnoid blood vessels.
      Increased AP sites and the inflammatory and stress protein brain responses were
      early and significant in dogs exposed to urban pollution. Oil combustion PM
      associated metals Ni and V were detected in the brain. There was an acceleration
      of Alzheimer's-type pathology in dogs chronically exposed to air pollutants.
      Respiratory tract inflammation and deteriorating olfactory and respiratory
      barriers may play a role in the observed neuropathology. These data suggest that
      Alzheimer's disease may be the sequela of air pollutant exposures and the
      resulting systemic inflammation.

PMID- 14692622
TI  - Stage-dependent expression of an angiogenic agent and vascular organization in
      experimental skin tumor development.
AB  - Increased angiogenesis and expression of antibodies to vascular endothelial
      growth factor (VEGF), an angiogenic agent, have been shown in the tumor
      development of many tissues. Areas of skin expressing VEGF and total volume of
      vessels expressing laminin in the wall were measured in chemical carcinogen
      exposed mice using CAS-200 morphometry apparatus having a sensitivity exceeding
      99% and reproducibility exceeding 99%. The area of VEGF expression was increased
      in carcinogen-exposed skin, dysplasia and in well-differentiated squamous cell
      carcinomas, but decreased in squamous cell carcinomas with decreased degree of
      differentiation. The vessel volume increased prior to the formation of tumors in
      carcinogen-exposed skin as well as in highly malignant neoplasms. In well
      differentiated squamous cell carcinomas with an expansive growth pattern, the
      vessels were parallel to the basal membrane, in moderately differentiated tumors
      the vessels were in the direction of tumor invasion, and in poorly differentiated
      tumors, active angiogenesis consisted of numerous, enlarged vessels within the
      tumor. This study showed increased VEGF expression and number of vessels
      occurring in early stages of skin tumor development, pointing to a role of
      angiogenesis in chemical risk assessment and in cancer prevention. Altered vessel
      structure and vessel arrangement were distinct in later stages of tumor growth
      and in malignant neoplasms, pointing to the utility of detailed vessel analysis
      in neoplasm characterization.

PMID- 14692623
TI  - Malignant myoepithelioma with a squamous epithelial component in the mammary
      gland of a cynomolgus monkey.
AB  - A solid mass arising from the mammary gland was found in a 7-year-old female
      cynomolgus monkey. Histologically, the mass consisted of 2 components: spindle
      shaped or ovoid sarcomatous cells and squamous epithelial cells. Metastatic
      nodules noted in the lung, liver and the gallbladder had the same histological
      features as the mammary mass. Immunohistochemistry revealed that the sarcomatous
      cells were positive for alpha-smooth muscle actin (alpha-SMA), vimentin,
      calponin, S-100 protein, epithelial membranous antigen (EMA), cytokeratin (large
      spectrum) and cytokeratin 14 (CK 14) in the cytoplasm, and p53, erbB-2 and
      progesterone receptor in the nuclei, but negative for desmin and estrogen
      receptor. The squamous epithelial cells were positive for EMA, cytokeratin (large
      spectrum) and CK 14, but negative for the rest. Both sarcomatous and squamous
      epithelial components were negative for glial fibrillary acidic protein (GFAP).
      Based on histological and immunohistochemical features, the present case was
      diagnosed as a malignant myoepithelioma with a squamous epithelial component in
      the mammary gland with distant metastases.

PMID- 14692624
TI  - Preclinical safety of recombinant human interleukin-18.
AB  - Recombinant human interleukin-18 (rHuIL-18) is currently in clinical trials for
      treatment of cancer. This report presents results of preclinical toxicity studies
      with rHuIL-18 in cynomolgus monkeys and recombinant murine IL-18 (rMuIL-18) in
      mice. The rHuIL-18 was administered intravenously in 1 or 2 different 5-day
      cycles at doses 0.3 to 75 mg/kg/day in monkeys. Decreases in red cell mass,
      neutrophil, and platelet counts, increases in monocyte and large unstained cell
      counts, and lymphoid hyperplasia in spleen and lymph nodes were mild, reversible,
      and likely related to the pharmacologic activity of IL-18. The only toxic effect
      was protein cast nephropathy, secondary to coprecipitation of administered IL-18
      and Tamm-Horsfall protein in the distal nephron, that only occurred at 75
      mg/kg/day. Other adverse effects of rHuIL-18 were related to strong
      immunogenicity in monkeys and were manifest only during a second dosing cycle.
      The rMuIL-18, at similar dosing levels and cycles in mice, resulted in reduced
      red cell mass, increased white blood cell counts, spleen and lymph node
      hyperplasia, and mild, reversible changes in intestine, liver, and lungs. Protein
      cast nephropathy occurred in mice at doses > or = 30 mg/kg/day. In conclusion,
      preclinical safety studies showed that rIL-18 was well tolerated at
      pharmacologically active doses in both monkeys and mice.

PMID- 14692625
TI  - Report of the IFSTP Professional Standards Subcommittee (PSSC).

PMID- 14692626
TI  - Comments on R. Karbe and R. L. Kerlin (2002). Cystic degeneration/spongiosis
      hepatis (Toxicol Pathol 30 (2), 216-227).
AB  - Karbe and Kerlin have questioned the classification of spongiosis hepatis as a
      preneoplastic lesion or even a benign neoplasm, designated as spongiotic
      pericytoma, and have proposed to use the term cystic degeneration for this lesion
      in rats and fish. However, the reclassification of spongiosis as cystic
      degeneration is unwarranted for several reasons. In the rat, spongiosis hepatis
      represents a specific pathomorphologic entity, originating from the
      perisinusoidal (Ito) cells; it may occur spontaneously in aged animals but its
      number and size increases significantly after exposure to various
      (hepato)carcinogens. Comparative morphological, immunohistochemical, and
      autoradiographic studies in rats exposed to N-nitrosomorpholine revealed that
      spongiosis hepatis is an integral part of larger proliferative Ito-cell
      aggregates showing an autonomous, progressive growth. The classification of
      spongiosis hepatis as a benign neoplasm is based on these findings that endorse
      and extend previous considerations on the preneoplastic or neoplastic nature of
      this lesion. Irrespective of the classification of spongiosis hepatis as a benign
      neoplastic or a preneoplastic lesion, there is compelling evidence for its
      reliability as a sensitive marker for (hepato)carcinogenic effects in rats and
      fish. The data collected by Karbe and Kerlin support rather than contradict the
      reliability of spongiosis hepatis as an effect marker for carcinogens.

PMID- 14692627
TI  - Recommended tissue list for histopathologic examination.

PMID- 14692628
TI  - Correspondance: Waddell WJ, Thresholds in chemical carcinogenesis: what are
      animal experiments telling us?

PMID- 14692629
TI  - Correspondance: Waddell WJ, Thresholds in chemical carcinogenesis: what are
      animal experiments telling us?

PMID- 14692630
TI  - Two-level hierarchy with sparsely and temporally coded patterns and its possible
      functional role in information processing.
AB  - We study the stability of two types of mixed states in an oscillator neural
      network model. Patterns to be stored are represented by complex variables whose
      amplitudes are either 0 (silent state) or 1 (firing state) and whose phases
      represent the timing of firing. The mixed states are defined in terms of a
      certain type of average over some specified number s of memory patterns. We
      define two types of such mixed states, each of which corresponds to a different
      type of restriction placed on this set of s memory patterns. The stability of
      each type is investigated both theoretically and numerically. We find that only
      one type of a mixed state, which consists of temporally correlated patterns, is
      stable. Finally, we discuss a possible functional role of such mixed states in
      information processing.

PMID- 14692631
TI  - Incremental training of first order recurrent neural networks to predict a
      context-sensitive language.
AB  - In recent years it has been shown that first order recurrent neural networks
      trained by gradient-descent can learn not only regular but also simple context
      free and context-sensitive languages. However, the success rate was generally low
      and severe instability issues were encountered. The present study examines the
      hypothesis that a combination of evolutionary hill climbing with incremental
      learning and a well-balanced training set enables first order recurrent networks
      to reliably learn context-free and mildly context-sensitive languages. In
      particular, we trained the networks to predict symbols in string sequences of the
      context-sensitive language [a(n)b(n)c(n); n > or = 1. Comparative experiments
      with and without incremental learning indicated that incremental learning can
      accelerate and facilitate training. Furthermore, incrementally trained networks
      generally resulted in monotonic trajectories in hidden unit activation space,
      while the trajectories of non-incrementally trained networks were oscillating.
      The non-incrementally trained networks were more likely to generalise.

PMID- 14692632
TI  - A model of dopamine modulated cortical activation.
AB  - Standard techniques from pharmacology and current theories on the biochemistry of
      dopamine (DA) are used to derive a new model of how DA modulates cortical
      activation. The model assumes that DA potentiates the glutamate response through
      the NMDA receptor and depresses the glutamate response through non-NMDA
      receptors. A static version of the model is used to examine the neurobiological
      plausibility of the Servan-Schreiber, Printz, and Cohen model [Science 249 (1990)
      892]. A dynamic version can be used to model many behaviors that are outside the
      domain of the static [Science 249 (1990) 892] model, including single-cell
      recording data. As a preliminary test of the model, we show that it can account
      for some single-cell recording data that examined the effects of DA on the firing
      rate of glutamatergic cortical cells.

PMID- 14692633
TI  - Inter-module credit assignment in modular reinforcement learning.
AB  - Critical issues in modular or hierarchical reinforcement learning (RL) are (i)
      how to decompose a task into sub-tasks, (ii) how to achieve independence of
      learning of sub-tasks, and (iii) how to assure optimality of the composite policy
      for the entire task. The second and last requirements are often under trade-off.
      We propose a method for propagating the reward for the entire task achievement
      between modules. This is done in the form of a 'modular reward', which is
      calculated from the temporal difference of the module gating signal and the value
      of the succeeding module. We implement modular reward for a multiple model-based
      reinforcement learning (MMRL) architecture and show its effectiveness in
      simulations of a pursuit task with hidden states and a continuous-time non-linear
      control task.

PMID- 14692634
TI  - Bounds on the number of hidden neurons in three-layer binary neural networks.
AB  - This paper investigates an important problem concerning the complexity of three
      layer binary neural networks (BNNs) with one hidden layer. The neuron in the
      studied BNNs employs a hard limiter activation function with only integer weights
      and an integer threshold. The studies are focused on implementations of arbitrary
      Boolean functions which map from [0, 1]n into [0, 1]. A deterministic algorithm
      called set covering algorithm (SCA) is proposed for the construction of a three
      layer BNN to implement an arbitrary Boolean function. The SCA is based on a unit
      sphere covering (USC) of the Hamming space (HS) which is chosen in advance. It is
      proved that for the implementation of an arbitrary Boolean function of n
      variables (n > or = 3) by using SCA, [3L/2] hidden neurons are necessary and
      sufficient, where L is the number of unit spheres contained in the chosen USC of
      the n-dimensional HS. It is shown that by using SCA, the number of hidden neurons
      required is much less than that by using a two-parallel hyperplane method. In
      order to indicate the potential ability of three-layer BNNs, a lower bound on the
      required number of hidden neurons which is derived by using the method of
      estimating the Vapnik-Chervonenkis (VC) dimension is also given.

PMID- 14692635
TI  - A new algorithm for online structure and parameter adaptation of RBF networks.
AB  - This paper deals with the problem of online adaptation of radial basis function
      (RBF) neural networks. A new adaptive training method is presented, which is able
      to modify both the structure of the network (the number of nodes in the hidden
      layer) and the output weights, as the algorithm proceeds. These adaptation
      capabilities make the algorithm suitable for modeling dynamical time varying
      systems, where not only the dynamics but also the operating region changes with
      time. Therefore, the important issue of extrapolation is faced successfully, but
      at the same time the algorithm takes care of the size of the network, by deleting
      the hidden node centers that remain inactive for a long time. The selection of
      the network centers is based on a fuzzy partition of the input space, which
      defines a number of fuzzy subspaces. The algorithm considers the centers of the
      fuzzy subspaces as candidates for becoming hidden node centers and makes the
      selections, so that at least one center is close enough to each input example.
      The proposed technique is illustrated through the application to time varying
      dynamical systems and is compared to other adaptive training methods.

PMID- 14692636
TI  - Relaxed conditions for radial-basis function networks to be universal
      approximators.
AB  - In this paper, we investigate the universal approximation property of Radial
      Basis Function (RBF) networks. We show that RBFs are not required to be
      integrable for the REF networks to be universal approximators. Instead, RBF
      networks can uniformly approximate any continuous function on a compact set
      provided that the radial basis activation function is continuous almost
      everywhere, locally essentially bounded, and not a polynomial. The approximation
      in L(p)(micro)(1 < or = p < infinity) space is also discussed. Some experimental
      results are reported to illustrate our findings.

PMID- 14692637
TI  - Singularities in mixture models and upper bounds of stochastic complexity.
AB  - A learning machine which is a mixture of several distributions, for example, a
      gaussian mixture or a mixture of experts, has a wide range of applications.
      However, such a machine is a non-identifiable statistical model with a lot of
      singularities in the parameter space, hence its generalization property is left
      unknown. Recently an algebraic geometrical method has been developed which
      enables us to treat such learning machines mathematically. Based on this method,
      this paper rigorously proves that a mixture learning machine has the smaller
      Bayesian stochastic complexity than regular statistical models. Since the
      generalization error of a learning machine is equal to the increase of the
      stochastic complexity, the result of this paper shows that the mixture model can
      attain the more precise prediction than regular statistical models if Bayesian
      estimation is applied in statistical inference.

PMID- 14692638
TI  - Study of distributed learning as a solution to category proliferation in Fuzzy
      ARTMAP based neural systems.
AB  - An evaluation of distributed learning as a means to attenuate the category
      proliferation problem in Fuzzy ARTMAP based neural systems is carried out, from
      both qualitative and quantitative points of view. The study involves two original
      winner-take-all (WTA) architectures, Fuzzy ARTMAP and FasArt, and their
      distributed versions, dARTMAP and dFasArt. A qualitative analysis of the
      distributed learning properties of dARTMAP is made, focusing on the new elements
      introduced to endow Fuzzy ARTMAP with distributed learning. In addition, a
      quantitative study on a selected set of classification problems points out that
      problems have to present certain features in their output classes in order to
      noticeably reduce the number of recruited categories and achieve an acceptable
      classification accuracy. As part of this analysis, distributed learning was
      successfully adapted to a member of the Fuzzy ARTMAP family, FasArt, and similar
      procedures can be used to extend distributed learning capabilities to other Fuzzy
      ARTMAP based systems.

PMID- 14692639
TI  - Converting general nonlinear programming problems into separable programming
      problems with feedforward neural networks.
AB  - In this paper we present a method for converting general nonlinear programming
      (NLP) problems into separable programming (SP) problems by using feedforward
      neural networks (FNNs). The basic idea behind the method is to use two useful
      features of FNNs: their ability to approximate arbitrary continuous nonlinear
      functions with a desired degree of accuracy and their ability to express
      nonlinear functions in terms of parameterized compositions of functions of single
      variables. According to these two features, any nonseparable objective functions
      and/or constraints in NLP problems can be approximately expressed as separable
      functions with FNNs. Therefore, any NLP problems can be converted into SP
      problems. The proposed method has three prominent features. (a) It is more
      general than existing transformation techniques; (b) it can be used to formulate
      optimization problems as SP problems even when their precise analytic objective
      function and/or constraints are unknown; (c) the SP problems obtained by the
      proposed method may highly facilitate the selection of grid points for piecewise
      linear approximation of nonlinear functions. We analyze the computational
      complexity of the proposed method and compare it with an existing transformation
      approach. We also present several examples to demonstrate the method and the
      performance of the simplex method with the restricted basis entry rule for
      solving SP problems.

PMID- 14692640
TI  - ARTMAP neural networks for information fusion and data mining: map production and
      target recognition methodologies.
AB  - The Sensor Exploitation Group of MIT Lincoln Laboratory incorporated an early
      version of the ARTMAP neural network as the recognition engine of a hierarchical
      system for fusion and data mining of registered geospatial images. The Lincoln
      Lab system has been successfully fielded, but is limited to target/non-target
      identifications and does not produce whole maps. Procedures defined here extend
      these capabilities by means of a mapping method that learns to identify and
      distribute arbitrarily many target classes. This new spatial data mining system
      is designed particularly to cope with the highly skewed class distributions of
      typical mapping problems. Specification of canonical algorithms and a benchmark
      testbed has enabled the evaluation of candidate recognition networks as well as
      pre- and post-processing and feature selection options. The resulting mapping
      methodology sets a standard for a variety of spatial data mining tasks. In
      particular, training pixels are drawn from a region that is spatially distinct
      from the mapped region, which could feature an output class mix that is
      substantially different from that of the training set. The system recognition
      component, default ARTMAP, with its fully specified set of canonical parameter
      values, has become the a priori system of choice among this family of neural
      networks for a wide variety of applications.

PMID- 14692641
TI  - Intralobar sequestration, revisited.

PMID- 14692642
TI  - Molecular insights into congenital disorders of the digestive system.
AB  - Recent work is providing new insights into molecular mechanisms of digestive
      system development and their alteration in clinically significant disorders. An
      understanding of these mechanisms has largely been gained through the use of
      animal models, because many of the basic processes required in embryogenesis are
      functionally conserved among species. Such conserved factors include cell-cell
      signaling pathways and the regulation of gene expression. Disruption of these
      pathways have been implicated in several congenital disorders of the digestive
      system, including Hirschsprung disease, malrotation, altered sphincter
      development, Meckel diverticulum, biliary atresia, Alagille syndrome, pancreatic
      heterotopias, and pancreatic agenesis. In this review, we highlight recent
      studies in digestive system development, which elucidate mechanisms underlying
      congenital disorders of the human digestive system.

PMID- 14692643
TI  - Beckwith-Wiedemann syndrome-associated hepatoblastoma: wnt signal activation
      occurs later in tumorigenesis in patients with 11p15.5 uniparental disomy.
AB  - Beckwith-Wiedemann syndrome (BWS) patients with chromosome 11p15.5 uniparental
      isodisomy (UPD) have an increased risk for developing embryonal tumors. UPD in
      these patients involves maternal loss of heterozygosity (LOH) and paternal
      duplication, which leads to tissue overgrowth and tumor development. Although
      11p15.5 UPD predisposes to tumorigenesis, the events leading to tumorigenesis in
      UPD patients remains unknown. We have examined two hepatoblastomas in the BWS
      patients with UPD to determine the sequence of genetic events. Constitutional
      11p15.5 LOH was detected in the blood or nonneoplastic liver of the BWS patients
      with hepatoblastoma. Mutation of beta-catenin gene (CTNNB1) was found in one
      hepatoblastoma. Although mutations in CTNNB1 were not found in the second
      hepatoblastoma, nuclear accumulation of beta-catenin was detected. However,
      mutation of CTNNB1 or nuclear accumulation of beta-catenin was not detected in
      the tissue with hepatomegaly which contains UPD cells. These data indicate that
      Wnt signal activation can be involved as a later event in BWS-associated
      hepatoblastoma involving 11p15.5 UPD.

PMID- 14692644
TI  - Immunohistochemical localization of endothelin-1 in human placenta from normal
      and growth-restricted pregnancies.
AB  - The purpose of this study was to investigate whether the localization of
      endothelin-1 (ET-1) immunoreactivity differs in human placental tissues from
      third-trimester normal and intrauterine growth restricted (IUGR) pregnancies.
      Immunohistochemistry for ET-1 was performed on human placentas from 30 IUGR and
      30 uncomplicated pregnancies matched for gestational age. The distribution and
      intensity of ET-1 immunoreactivity was assessed by a semiquantitative scoring
      system. Doppler flow velocity waveform analysis of the umbilical artery was
      performed in each patient before delivery. ET-1 was localized diffusely in
      placental specimens from normal and IUGR pregnancies. The localization of ET-1
      immunoreactivity was significantly higher in the capillary endothelial cells of
      villi as well as in the endothelial, decidual, and trophoblastic cells of the
      basal plate in placentas from normal pregnancies than from IUGR pregnancies.
      There was no significant difference in placental ET-1 immunoreactivity between
      IUGR pregnancies with normal and abnormal umbilical artery Doppler flow velocity
      waveforms. Placental ET-1 immunoreactivity was significantly higher in the
      decidual and trophoblastic cells of the basal plate and the capillary endothelial
      cells of villi in normal pregnancies than in IUGR pregnancies with normal
      umbilical artery Doppler flow velocity waveforms. However, only the decidual and
      trophoblastic cells of the basal plate demonstrated significantly higher abundant
      localization of ET-1 immunoreactivity in normal pregnancies than in IUGR
      pregnancies with abnormal umbilical artery Doppler flow velocity waveforms. In
      conclusion, our findings suggest that the lower expression of ET-1 in placental
      tissues from IUGR pregnancies might be secondary to an adaptive mechanism to
      reduce the vasoconstrictor effect of ET-1.

PMID- 14692645
TI  - Intralobar sequestration of the lung is a congenital anomaly: anatomopathological
      analysis of four cases diagnosed in fetal life.
AB  - The origin of intralobar sequestration of the lung (ILS)-whether congenital or
      acquired--has often been controversial, since firm anatomical evidence of
      prenatal origin has been sparse. We describe four cases in which anomalous
      arterial supply from the aorta to abnormally echogenic lower lung lobes was
      demonstrated on routine antenatal ultrasound examination, and the diagnosis of
      ILS was subsequently confirmed by postmortem examination including bronchography
      of the fetuses at between 20 and 23 wk. One right-sided lesion was supplied from
      a branch of the coeliac axis, and three left-sided lesions were supplied from the
      thoracic aorta. In two cases, the arterial supply was shown to be multiple. All
      lesions were situated in the lower lobes. They showed a cystic transformation of
      the affected lung tissue which was histologically indistinguishable from cases
      diagnosed as congenital cystic adenomatoid lesion (CCAM) at the same gestational
      age, but clearly different from that seen in bronchial obstruction due to
      laryngeal stenosis at that age. Similar vascular lesions have been reported in
      otherwise normal lungs. The character of the anomalous arterial vessels is
      consistent with origin from the embryonic splanchnic plexus. The precise sequence
      of pathogenetic events is unclear but there appears to be a close relationship of
      this condition not only with CCAM but also with the condition of anomalous
      arterial supply to the lower lobe.

PMID- 14692646
TI  - Histopathology of congenital hyperinsulinism: retrospective study with genotype
      correlations.
AB  - The majority of the most severe cases of congenital hyperinsulinism (HI) are
      caused by defects in the beta-cell adenosine triphosphate (ATP)-sensitive
      potassium channel and usually require pancreatectomy to control blood sugar
      levels. In contrast to the recent advances in understanding the pathophysiology
      and genetic bases of HI, the histologic classification of this condition remains
      controversial. A recent proposal to classify the HI pancreata into diffuse and
      focal forms has drawn much interest because of its relative simplicity and its
      good correlation with the genetic abnormalities. We undertook a retrospective
      study to determine whether this classification scheme could be applied to 38
      pancreata resected for HI at our institution. We also obtained leukocyte genomic
      DNA from 29 cases and screened the exons of ABCC8 and KCNJ11 genes for the
      presence of mutations. Nineteen cases (50.0%) were histologically classified as
      diffuse HI and 14 cases (36.8%) were categorized as focal form. The mutational
      analysis revealed that 14 of the 16 diffuse cases analyzed had either homozygous
      or compound heterozygous mutations of ABCC8 or KCNJ11 and 7 of 10 focal cases had
      only the paternally inherited mutations, consistent with the previous
      observations. Two patients (5.3%) had normal pancreatic histology but had
      persistent hypoglycemia postoperatively, leaving the possibility of residual
      focal lesion. Three of 38 cases (7.9%) did not fit well into either diffuse or
      focal category. Two cases differed from the described pattern for the diffuse
      form in that the nuclear enlargement was confined to a single area of the
      pancreas. The other case had a focal lesion but beta-cell nuclear enlargement was
      present in nonadjacent areas. Mutations for typical diffuse or focal HI were not
      identified in two of these three equivocal cases. We conclude from this study
      that nearly 90% of HI cases can be classified into either a diffuse or a focal
      form. However, a small percentage of cases represented a diagnostic challenge.

PMID- 14692647
TI  - Maternal diabetes: effects on embryonic vascular development--a vascular
      endothelial growth factor-A-mediated process.
AB  - Major congenital malformations, many of which result from abnormal cardiovascular
      patterning, remain the leading cause in infant mortality and morbidity. Targeted
      mutations of several genes (including VEGF and VEGF receptors) and certain
      teratogenic agents (including excess alpha-D-glucose) give rise to embryonic
      lethal phenotypes associated with failure in the formation of a functional
      vitelline circulation and aberrant organogenesis. Our work to date has
      demonstrated that yolk sac vasculopathy and failure of endocardial cushion
      epithelial-mesenchymal transformation occurs in hyperglycemic conditions in
      murine whole conceptus culture and in embryos from streptozotocin-induced
      diabetic mice. These cardiovascular abnormalities are associated with changes in
      expression and phosphorylation state of adhesion molecules such as platelet
      endothelial growth factor-1 and expression of growth factors such as vascular
      endothelial growth factor (VEGF-A). Further understanding of the effects of
      maternal diabetes on yolk sac and embryonic vasculogenesis/angiogenesis and
      organogenesis may lead to novel approaches in treating and preventing major birth
      defects.

PMID- 14692648
TI  - Aspirin intoxication in a child associated with myocardial necrosis: is this a
      drug-related lesion?
AB  - A 5-year-old girl with a mild upper airways infection was admitted to the
      hospital because of sudden vomiting and drowsiness that evolved to stupor; she
      was dehydrated, hypotensive, and tachypneic; laboratory tests revealed
      noncompensated lactic acidosis. She also had hypoglycemia followed by
      hyperglycemia, and progressive bradycardia leading to reversible cardiac arrest.
      Her clinical condition complicated by sinus bradycardia, ventricular tachycardia,
      third-degree atrioventricular blockage and lethal asystole. At the final stage of
      her illness, the serum salicylate concentration was 383.8 mcg/mL. Based on this
      single data, a retrospective toxicological analysis estimated a theoretical peak
      level of serum salicylate of approximately 1570 mcg/mL (therapeutic range, 20-250
      mcg/mL) although the real amount of aspirin that this child ingested is difficult
      to calculate because aspirin is a drug that shows a so-called zero order
      kinetics. At autopsy, the most striking finding was multiple foci of coagulative
      necrosis involving the entire thickness of the myocardium with scant inflammatory
      infiltrate composed mainly of macrophages and polymorphonuclear leukocytes. The
      morphologic characteristics of the myocardial lesion in addition to salicylate
      blood levels suggests the possibility of an adverse drug reaction of the type
      acute toxic myocarditis.

PMID- 14692649
TI  - Unilateral transverse arm defect with subterminal digital nubbins.
AB  - We present a case of unilateral terminal transverse forearm deficiency with
      subterminal digit-like nubbins, identified in a fetus from a pregnancy terminated
      electively in the second trimester because the distal right arm and hand could
      not be seen by ultrasound and were presumed to be absent. Pathologic evaluation
      showed distal transverse shortening, tapering to a point in the mid-forearm. Five
      primitive digital nubbins were present, located just proximal to the tapered
      point. The arm vessels appeared normal histologically, and the amnion showed no
      evidence of intrauterine disruption. Histologic examination of the nubbins
      revealed osteocartilaginous tissue, never described previously within digital
      nubbins. This fetus has the rare phenotype of terminal transverse limb defects
      with residual nubbins, but differs in that the nubbins are not at the tip of the
      terminal transverse limb defect.

PMID- 14692650
TI  - Facio-auriculo-vertebral sequence in association with DiGeorge sequence,
      Rokitansky sequence, and Dandy-Walker malformation: case report.
AB  - Extreme variability of expression is characteristic of the facio-auriculo
      vertebral sequence. Sporadic and familial cases have been reported with obvious
      etiologic heterogeneity. Most reports in the literature are of clinical cases.
      The purpose of this paper is to present a fetal autopsy case report of the facio
      auriculo-vertebral sequence in association with DiGeorge sequence, Rokitansky
      sequence, and Dandy-Walker malformation. A standard neonatal autopsy was
      performed on a macerated female fetus, gestational age 29 wk. External
      examination of the fetus revealed hypoplastic right face, low-set microtic right
      ear, and macrostomia. Internal examination showed hypoplastic thymus and lungs, a
      type I truncus arteriosus, and ventricular septal defect. Both kidneys showed
      evidence of pelvi-ureteric junction obstruction. The ovaries and fallopian tubes
      were present with an absent uterus and vagina (Rokitansky sequence). In addition,
      Dandy-Walker malformation was identified. Microscopically, a single hypoplastic
      parathyroid gland was noted and there was cystic renal dysplasia. We report the
      sixth case of the facio-auriculo-vertebral sequence in association with
      Rokitansky sequence and the first case of this sequence in association with Dandy
      Walker malformation. In addition, features of DiGeorge sequence were present.

PMID- 14692651
TI  - The 2G single nucleotide polymorphism (SNP) in the MMP-1 promoter contributes to
      high levels of MMP-1 transcription in MCF-7/ADR breast cancer cells.
AB  - Degradation of stromal collagens in the extracellular matrix is mediated largely
      by matrix metalloproteinase-1 (MMP-1; collagenase-1), and high constitutive
      levels of MMP-1 in breast cancer correlate with a poor prognosis and invasive
      disease. MMP-1 expression is, in part, controlled by the mitogen-activated
      protein kinase (MAPK) pathway(s), which may target several activator protein-1
      (AP-1) and polyoma enhancing activity-3/E26 virus (PEA3/ETS) sites within the
      promoter. An additional ETS site in the MMP-1 promoter is conferred by a single
      nucleotide polymorphism (SNP) at -1607 bp, when two guanines (5'-GGAT-3'; '2G
      allele/SNP') are present instead of one guanine (5'-GAT-3'; '1G allele/SNP').
      This SNP is adjacent to an AP-1 site at -1602 bp, and in the presence of the 2G
      allele (ETS site), these sites cooperate to induce higher levels of
      transcription. ERK 1/2 is one component of the MAPK pathway and is constitutively
      active in MCF-7/ADR breast cancer cells, which are 1G/2G heterozygotes. This
      study demonstrates that when these cells are treated with PD098059, an ERK
      specific inhibitor, MMP-1 mRNA levels are significantly decreased, suggesting
      that high constitutive expression of MMP-1 in these cells results from continuous
      ERK 1/2 activation. Using transient transfection, we determined that this
      signaling pathway targets different AP-1/ETS sites, depending upon which allele
      is present. Furthermore, in these cells, the AP-1 site at -1602 bp enhances
      transcription in the presence of the 2G SNP, but represses transcription from the
      1G SNP. Finally, inhibiting ERK signaling and MMP-1 expression blocks type I
      collagen degradation and reduces the invasive ability of the MCF-7/ADR cells. We
      conclude that ERK 1/2 signaling and the 2G SNP mediate high levels of MMP-1
      expression, which may contribute to the invasive potential of these breast cancer
      cells.

PMID- 14692652
TI  - Patients with recurrent breast cancer: does the primary axillary lymph node
      status predict more aggressive tumor progression?
AB  - BACKGROUND: The extent of axillary lymph node involvement represents the foremost
      important prognostic parameter in primary breast cancer, and, thus, is one of the
      main determinants for subsequent systemic treatment. Nevertheless, the relevance
      of the initial axillary lymph node status on survival after disease recurrence is
      discussed controversially. Persisting prognostic impact after relapse would
      identify lymph node status as a marker for tumor biology, in contrast to a simply
      time-dependent phenomenon. METHOD: Retrospective analysis of 813 patients with
      locoregional or distant recurrence of primary breast cancer, who were primarily
      diagnosed with their disease at the I. Frauenklinik, Ludwig-Maximilians
      University, Munich, and the University Hospital in Berlin-Charlottenburg,
      Germany, between 1963 and 2000. To be eligible, patients were required to have
      been treated for resectable breast cancer free of distant disease at the time of
      primary diagnosis, and must have undergone systematic axillary lymph node
      dissection. Patients with unknown tumor size or nodal status were excluded from
      the study. All data were gathered contemporaneously and compared with original
      patients files, as well as the local cancer registry, ensuring high quality of
      data. The median observation time was 60 (standard deviation 44) months. RESULTS:
      At time of primary diagnosis, 273 patients (33.6%) were node-negative, while
      axillary lymph node metastases were detected in 540 patients (66.4%). In
      univariate analysis tumor size, axillary lymph node status, histopathological
      grading, hormone receptor status, as well as peritumoral lymphangiosis and
      haemangiosis carcinomatosa were significantly correlated with survival after
      relapse (all, P < 0.0001). Kaplan-Meier analysis estimated the median survival
      time after relapse in node-negative patients to be 42 months (31-52 months, 95%
      CI), and 20 months in patients with 1-3 axillary lymph node metastases (16-24
      months, 95% CI), compared to 13 months in patients with at least 4 involved
      axillary nodes (12-15 months, 95% CI). Multivariate logistic regression analysis,
      allowing for tumor size, axillary lymph node status, histopathological grading,
      presence of lymphangiosis carcinomatosa, relapse site and disease-free interval
      confirmed all parameters, except of histopathological grading (P = 0.14), as
      significant, independent risk factors for cancer associated death. Subgroup
      analyses, accounting for site of relapse and duration of disease-free interval,
      confirmed primary lymph node status as independent predictor for cancer
      associated death after relapse. CONCLUSION: Lymph node involvement at primary
      diagnosis of breast cancer patients predicts an unfavorable outcome after first
      recurrence, independently of the site of relapse and disease-free interval. These
      observations support the hypothesis that primary lymph node involvement is not a
      merely time-dependent indicator for tumor progression, but indicates tumors with
      aggressive biological behavior.

PMID- 14692653
TI  - MR imaging-guided focused ultrasound surgery of breast cancer: correlation of
      dynamic contrast-enhanced MRI with histopathologic findings.
AB  - PURPOSE: To assess the value of dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI) parameters to monitor residual tumor following non-invasive MRI
      guided focused ultrasound surgery (MRIgFUS) of breast tumors. METHODS: DCE-MRI
      data were acquired before and after the MRIgFUS treatment of small breast tumors
      (d < 3.5 cm) for 17 patients. The lesion was surgically resected and the presence
      of residual tumor was determined by histopathological analysis. The percentage of
      residual tumor was correlated with three DCE-MRI parameters measured at the
      maximally enhancing site of each tumor: increase in signal intensity (ISI),
      maximum difference function (MDF) and positive enhancement integral (PEI).
      RESULTS: A good correlation was found between the ISI (r = 0.897), MDF (r =
      0.789) and PEI (r = 0.859) parameters and the percentage of residual viable tumor
      determined by histopathology. A receiver operator characteristic curve analysis
      yielded a cutoff value for ISI at 20% with a sensitivity of 77% and a specificity
      of 100%. CONCLUSION: These results suggest that parameters from DCE-MRI data
      could provide a reliable non-invasive method for assessing residual tumor
      following MRIgFUS treatment of breast tumors.

PMID- 14692654
TI  - Estrogenic effects of toremifene and tamoxifen in postmenopausal breast cancer
      patients.
AB  - Intrinsic estrogenicities of the selective estrogen receptor modulators (SERMs)
      toremifene 60 mg daily or 200 mg daily and tamoxifen 20 mg daily (TOR60, TOR200
      and TAM20) were compared in a randomized clinical study in postmenopausal women
      with advanced breast cancer. The study was open label in three parallel groups.
      Variables for analysis were serum follicle stimulating hormone (FSH), luteinizing
      hormone (LH), sex hormone binding globulin (SHBG), estradiol (E2), antithrombin
      III (AT III), aspartate aminotransferase (ASAT) and vaginal cytology. Clinical
      efficacy and safety have been reported earlier. A total of 648 patients were
      randomized (221 to TOR60, 212 to TOR200 and 215 to TAM20). Sera were available
      for the analysis from 148, 165 and 156 and for vaginal cytology from 98, 93 and
      86 patients, respectively. All treatment regimens showed tissue-specific and dose
      dependent estrogen agonist effect. In the primary measure of in vivo
      estrogenicity, effect on hypothalamus-pituitary-axis, all three treatment
      regimens decreased serum FSH (p < 0.001). TOR200 was more potent than the two
      other treatments (p < 0.05), but surprisingly, TAM20 was more estrogenic than
      TOR60 (p < 0.001). As could be expected in postmenopausal women, the treatments
      had no effect on mean serum E2 concentrations and decrease of serum LH was
      similar to that of FSH. Estrogenic effect on the liver was seen as dose-dependent
      increase of SHBG with statistically significant differences between the treatment
      groups (p < 0.001). Trends of transient ASAT elevations in TOR200 group (p =
      0.07) and in all treatment groups AT III decrease (p = 0.1) were seen in the
      beginning of the treatment. TOR60 or TAM20 did not have an effect on mean ASAT
      values, and AT III decreased in TAM20 group more than in the two other groups (p
      = 0.1 compared to TOR60 and p < 0.05 compared to TOR200). Estrogenic effects on
      vaginal superficial cells were higher in TOR60 and TOR200 groups when compared to
      TAM20 (p < 0.05). Toremifene and tamoxifen had tissue-specific and partially dose
      dependent estrogenic effects in hypothalamus-pituitary-axis, in the liver and in
      the vaginal epithelium of postmenopausal women. In some tissues tamoxifen 20 may
      be more estrogenic than toremifene 60 mg/day.

PMID- 14692655
TI  - Studies of the potential utility of Ki67 as a predictive molecular marker of
      clinical response in primary breast cancer.
AB  - INTRODUCTION: Objectives were to characterise the relationship of the
      proliferation marker Ki67 with response to systemic treatment in early breast
      cancer and to assess its clinical utility, using fine needle aspirates. MATERIALS
      AND METHODS: Hundred and six women were treated with primary tamoxifen (n = 33),
      chemotherapy (n = 33) or chemotherapy and tamoxifen (n = 40). Treatment was not
      randomised and response was assessed clinically. Ki67 was evaluated prior to
      treatment and at Day 14 or 21 after commencing treatment. To assess
      reproducibility, Ki67 was evaluated in repeat FNAs taken from 37 untreated
      patients. RESULTS: The percentage change in Ki67 in first 21 days was different
      between responders and non-responders for patients treated with tamoxifen (p =
      0.007) and chemotherapy (p = 0.005) but not for chemoendocrine treatment (p =
      0.062). The reproducibility study indicated that a decrease to 36% or less of the
      pre-treatment Ki67 value in an individual patient was required for it to be
      regarded as a statistically significant change. A significant decrease in Ki67
      was seen in responding patients treated with chemotherapy (p = 0.026) and
      chemoendocrine treatment (p = 0.041). Positive and negative predictive values for
      response were 85 and 59% for chemotherapy patients and 88 and 54% for
      chemoendocrine patients, respectively. CONCLUSION: Ki67 is unlikely to be useful
      as a predictive marker in individual patients. Further molecular markers that
      predict lack of response continue to be required.

PMID- 14692656
TI  - Potent killing of paclitaxel- and doxorubicin-resistant breast cancer cells by
      calphostin C accompanied by cytoplasmic vacuolization.
AB  - Drug resistance is a major impediment to the successful treatment of breast
      cancer using chemotherapy. The photoactivatable drug calphostin C has shown
      promise in killing select drug-resistant tumor cells lines in vitro. To assess
      the effectiveness of this agent in killing doxorubicin- or paclitaxel-resistant
      breast tumor cells and to explore its mode of action, MCF-7 cells were exposed to
      increasing concentrations of either doxorubicin or paclitaxel until maximum
      resistance was obtained. This resulted in the creation of isogenic drug-resistant
      MCF-7TAX and MCF-7DOX cell lines, which were approximately 50- and 65-fold
      resistant to paclitaxel and doxorubicin, respectively. Interestingly, calphostin
      C was able to kill MCF-7TAX cells as efficiently as wildtype MCF-7 cells (IC50s
      were 9.2 and 13.2 nM, respectively), while MCF-7DOX cells required a 5-fold
      higher concentration of calphostin C to achieve the same killing (IC50 = 64.2
      nM). Consistent with their known mechanisms of action, paclitaxel killed tumor
      cells by inducing mitotic arrest and cell multinucleation, while doxorubicin
      induced plasma membrane blebbing and decreased nuclear staining with propidium
      iodide. In contrast, cytoplasmic vacuolization accompanied cell killing by
      calphostin C in these cell lines, without the induction of caspase-8 or PARP
      cleavage or the release of cytochrome c from mitochondria. Calphostin C had
      little effect on the uptake of either paclitaxel or doxorubicin by the cells.
      Taken together, the above data suggests that calphostin C is able to potently
      kill drug-resistant breast tumor cells through a mechanism that may involve the
      induction of cytoplasmic vacuolization, without activation of typical apoptotic
      pathways. Consequently, calphostin C may prove useful clinically to combat tumor
      growth in breast cancer patients whose tumors have become unresponsive to
      anthracyclines or taxanes, particularly in association with photodynamic therapy.

PMID- 14692657
TI  - Cytokine signaling/transcription factor cross-talk in T cell activation and Th1
      Th2 differentiation.
AB  - The secretion of interleukin 2 (IL-2) is a key event in T cell activation. IL-2
      allows T cells to enter into the S phase of the cell cycle and divide. After the
      activation phase takes place, T lymphocytes proliferate and differentiate to
      generate effector T cells. Thereby, T helper (Th) precursor cells, which are
      functionally immature, may become Th1 or Th2 effector cells. These subsets are
      responsible for cell-mediated immunity and humoral responses, respectively. Both
      T cell activation and Th differentiation are processes that depend on changes in
      the pattern of gene expression. The expression and changes in the genes
      responsible for these events are regulated by transcription factors. This review
      will focus on both the transcription factors involved in the control of IL-2 as
      well as those that are key to T helper differentiation.

PMID- 14692658
TI  - Viral strategies in modulation of NF-kappaB activity.
AB  - Activation of the nuclear factor (NF)-kappaB transcription factor family in
      response to different stimuli, such as inflammatory cytokines, stress inducers or
      pathogen products, results in host innate and adaptive immunity. NF-kappaB plays
      a central role in promoting the expression of genes involved in inflammatory,
      immune and apoptotic processes, including those encoding cytokines, chemokines,
      cytokine receptors and proteins involved in antigen presentation. Although the
      main function of NF-kappaB is to activate specific genes in the cells of the
      immune system, its role in controlling the host cell cycle makes NF-kappaB an
      interesting target for pathogenic viruses. Some viruses take advantage of the
      anti-apoptotic properties of NF-kappaB to escape host defence mechanisms, others
      use apoptosis to spread. This review describes the role of the NF-kappaB family
      in immune responses, the mechanism of NF-kappaB activation, and different
      strategies that viruses have developed to modulate the NF-kappaB pathway in order
      to facilitate and enhance viral replication and avoid host immune responses.

PMID- 14692659
TI  - The immunological synapse.
AB  - The induction of a proper adaptive immune response is dependent on the correct
      transfer of information between antigen-presenting cells (APCs) and antigen
      specific T cells. Defects in information transfer may result in the development
      of diseases, e.g. immunodeficiencies and autoimmunity. A distinct 3-dimensional
      supramolecular structure at the T cell/APC interface has been suggested to be
      involved in the information transfer. Due to its functional analogy to the
      neuronal synapse, the structure has been termed the "immunological synapse" (IS).
      Here, we review molecular aspects concerning IS formation, appearance, and
      cessation. In addition, proposed functions of the IS are discussed. The process
      of IS formation occurs in a sequential manner, initially causing a remarkable
      large-scale redistribution of a number of integral membrane and cytosolic
      proteins. At the T cell/APC interface the structure comprises in its nascent
      stage a non-random pattern of protein distribution. The protein pattern is
      regulated during development of the mature IS and is finally organized into
      concentric rings of co-receptors and adhesive molecules surrounding the T cell
      antigen receptor (TCR). The relocations of proteins are influenced by passive as
      well as active mechanisms. Considering the IS as a device enabling cell-cell
      communication, clarification of its exact function is of huge general as well as
      therapeutic interest.

PMID- 14692661
TI  - New insights into the pathophysiology and in vivo function of IgG Fc receptors
      through gene deletion studies.
AB  - Fc-receptors for IgG (FcyRs) are critically involved at multiple stages of an
      immune response, ranging from antigen presentation and regulation of antibody
      production to the end-stage effector mechanisms of inflammation. IgG
      autoantibodies that are detectable in the majority of autoimmune diseases are
      ligands for FcgammaRs. The three classes, FcgammaRI, FcgammaRII, and FcgammaRIII,
      vary in their antibody affinity, cellular expression and in vivo function. We
      review the current knowledge on the regulation and diverse functions of the
      distinct FcgammaRs and describe the evidence of their important immunoregulatory
      roles in autoimmunity based on recent work in animal models.

PMID- 14692660
TI  - Dynamic control of B lymphocyte development in the bursa of fabricius.
AB  - The chicken is a foundational model for immunology research and continues to be a
      valuable animal for insights into immune function. In particular, the bursa of
      Fabricius can provide a useful experimental model of the development of B
      lymphocytes. Furthermore, an understanding of avian immunity has direct practical
      application since chickens are a vital food source. Recent work has revealed some
      of the molecular interactions necessary to allow proper repertoire
      diversification in the bursa while enforcing quality control of the lymphocytes
      produced, ensuring that functional cells without self-reactive immunoglobulin
      receptors populate the peripheral immune organs. Our laboratory has focused on
      the function of chB6, a novel molecule capable of inducing rapid apoptosis in
      bursal B cells. Our recent work on chB6 will be presented and placed in the
      context of other recent studies of B cell development in the bursa.

PMID- 14692662
TI  - Development and selection of T cells: how many subsets? How many rules?
AB  - Since the discovery indicating that thymus-derived lymphocytes (T cells) can be
      divided into two subpopulations: CD8+ (killer) and CD4+ (helper) cells,
      subsequent studies revealed a bewildering heterogeneity of T cells. In the
      present review an attempt is made to present the current picture of T cell
      heterogeneity, introduce some order into the nomenclature, and summarize the
      rules behind the development and selection of different currently recognized T
      cell subsets.

PMID- 14692663
TI  - Efficacy of procalcitonin measurement in patients after total thyroidectomy due
      to medullary thyroid carcinoma.
AB  - Procalcitonin (PCT) is a protein synthetized by the thyroid C cells, inside which
      it is cut into calcitonin (CT) and catacalcin. It remains undetectable in serum
      in normal conditions. Its level increases during inflammation and in small cell
      lung cancer. There have been studies suggesting that the PCT level increases in
      medullary thyroid carcinoma (MTC). So far there have been no reports that would
      assess the usefulness of PCT detection in MTC. Our aim was to evaluate the
      usefulness of serum PCT assays in patients with MTC. We investigated 24 patients
      at 17-78 years of age, all after total thyroidectomy due to MTC. All patients had
      serum CT concentrations measured by radioimmune assay. The upper limit of the CT
      level was 60 pg/ml. The serum PCT was evaluated with an immunochromatographic
      kit. The reaction was considered positive when the PCT level exceeded 0.5 ng/ml.
      In all cases the C-reactive protein (CRP) serum level was measured. The
      statistical analysis was performed with Statistica 5.1G. The CT levels in all
      patients varied from 0 to 1410, mean 603.8 pg/ml. In 8 patients the CT level was
      within normal range, in 6 patients it was marginally, and in 10 patients markedly
      elevated. The PCT test was considered positive in 16 patients. There was
      correlation among serum PCT and CT concentrations (Spearman test, p<0.0001). The
      PCT levels varied considerably among patients with normal, marginally and
      markedly elevated CT levels (Kruskal-Wallis test, p=0.0013). All patients had
      normal CRP values. Fisher's exact test revealed a correlation between serum PCT
      and CT increase (p=0.04). Further studies on a larger group of patients should be
      considered; thus, the PCT assay can be considered useful in cases of unclear CT
      concentration.

PMID- 14692664
TI  - CD80 and CD86 expression on LPS-stimulated monocytes and the effect of CD80 and
      CD86 blockade on IL-4 and IFN-gamma production in nonatopic bronchial asthma.
AB  - CD80 and CD86 seem to play an important role in the allergen-induced secretion of
      interleukin (IL)-5 and IL-13. Up to now, the expressions of CD80 (B7.1) and CD86
      (B7.2) on monocytes and the kinetics of the expression of these molecules on
      lipopolysaccharide-stimulated monocytes in nonatopic asthma have not been
      defined. Using monoclonal antibodies, we have compared the expressions of CD80
      (B7.1) and CD86 (B7.2) on the monocytes of healthy persons and nonatopic
      asthmatic patients. We have also assessed the effect of CD80 and CD86
      inactivation on IL-4 and interferon (IFN)-gamma production in nonatopic
      asthmatics and healthy subjects. We found that a low expression of CD80 (1.64 +/-
      0.65 vs. 3.53 +/- 1.43%) and a moderate expression of CD86 (41.25 +/- 13.4 vs.
      49.46 +/- 11.49%) on the studied monocytes were characteristic for asthma. In
      nonatopic asthma patients inactivation of CD80 or CD86 blockade significantly
      reduced IFN-gamma production by T lymphocytes (p < 0.02; p < 0.03). In both the
      studied groups, anti-CD80 antibodies did not diminish T lymphocyte production of
      IL-4. However, anti-CD86 antibodies significantly (p < 0.04) reduced the IL-4
      concentration in culture supernatants. Our results confirm that both the CD80 and
      CD86 molecules play an important role in the maintenance and amplification of the
      inflammatory process. It suggests that in the inflammatory process that occurs in
      nonatopic bronchial asthma, Th1 as well as Th2 lymphocytes are equally important.

PMID- 14692665
TI  - Beating negativity and developing cohesiveness.

PMID- 14692666
TI  - Hope for the holidays.

PMID- 14692667
TI  - Salary and staffing surveys help estimate compensation and future trends.
AB  - CALCULATING COMPENSATION for perioperative nurses can be complicated because of
      their unique workplace situations. THIS SALARY SURVEY uses a multiple regression
      model to examine how a variety of variables, including job title, education,
      certification, experience, and geographic region, affect of other forms of
      compensation (eg, overtime, shift differential, on-call compensation) on average
      base compensation rates.

PMID- 14692668
TI  - Primary total hip arthroplasty.
AB  - TOTAL HIP ARTHROPLASTY (THA) has been proven to decrease a patient's pain and
      improve function and quality of life. This procedure has been performed in the
      United States since 1960. Follow-up data suggest long-term success with a
      decreasing rate of complications and low rate of revision. MORE THAN 168,000 THA
      procedures are performed in the United States every year. There is an 80% chance
      these hip replacements will last at least 20 years. CURRENT IMPROVEMENTS in hip
      designs, surgical techniques, fixation methods, prophylactic therapies,
      preadmission education, and rehabilitation have contributed to improved patient
      outcomes.

PMID- 14692669
TI  - Horizontal violence among nurses in the operating room.
AB  - MANY NURSES report that sabotage is a common event in the OR, and the level of
      sabotage present in the OR may have an effect on overall job satisfaction among
      perioperative nurses. THIS STUDY looked at the relationship between the presence
      of sabotage in the OR and job satisfaction levels reported by a group of
      perioperative nurses in New Jersey. STUDY RESULTS found that although sabotage is
      reported as common in the OR, the presence of sabotage is not significantly
      associated with reported job satisfaction.

PMID- 14692670
TI  - Morbid obesity--psychosocial aspects and surgical interventions.
AB  - MORBID OBESITY has a significant impact on the health, psychosocial well-being,
      longevity, and quality of life of those affected. BARIATRIC SURGERY is not a cure
      for obesity; however, surgical interventions can offer the potential for long
      term weight-loss success for individuals who are obese. CAREGIVERS should be
      prepared to meet both the physiological and psychological needs of these
      patients. EDUCATION is key to helping the public understand that obesity is a
      chronic disease, and bariatric surgery should be viewed no differently than
      surgery for other chronic diseases.

PMID- 14692671
TI  - Using a personal digital assistant to streamline the OR workload.
AB  - PERSONAL DIGITAL ASSISTANTS (PDAs), are handheld minicomputers used for tasks
      such as referencing, documentation, and data storage and retrieval. THESE DEVICES
      can help perioperative nurses solve problems associated with updating,
      maintaining, and retrieving surgical preference cards and accessing treatment and
      medication references. CHOOSING A PDA and accessories, finding basic software,
      and writing a perioperative nursing program can be painless, even for a novice.
      NURSING DOCUMENTATION can be accelerated and streamlined with the use of PDAs,
      which leaves perioperative nurses more time for quality patient care.

PMID- 14692672
TI  - Blood transfusion in the OR--are you practicing safely?

PMID- 14692674
TI  - Global burden of trachoma and economics of the disease.
AB  - Interest in the economics of trachoma is high because of the refinement of a
      strategy to control trachomatous blindness, an ongoing global effort to eliminate
      incident blindness from trachoma by 2020, and an azithromycin donation program
      that is a component of trachoma control programs in several countries. This
      report comments on the economic distribution of blindness from trachoma and adds
      insight to published data on the burden of trachoma and the comparative costs and
      effects of trachoma control. Results suggest that 1) trichiasis without visual
      impairment may result in an economic burden comparable to trachomatous low vision
      and blindness so that 2) the monetary burden of trachoma may be 50% higher than
      conservative, published figures; 3) within some regions more productive economies
      are associated with less national blindness from trachoma; and 4) the ability to
      achieve a positive net benefit of trachoma control depends importantly on the
      cost per dose of antibiotic.

PMID- 14692675
TI  - Application of molecular tools in the control of blinding trachoma.
AB  - The use of anti-chlamydial antibiotics for trachoma control is based on the
      assumption that most people with clinically active disease have conjunctival
      infection with Chlamydia trachomatis. In high prevalence areas, this is generally
      true. As prevalence decreases, however, the positive predictive value of clinical
      signs for C. trachomatis infection also decrease. In this paper, the case for
      using laboratory assays to guide trachoma control strategies is presented,
      molecular methods for diagnosis (such as a ligase chain reaction and a polymerase
      chain reaction [PCR]) are compared with earlier techniques, and recent findings
      of ongoing studies using a quantitative PCR are reviewed. In addition, the
      contribution of genotyping to our understanding of the epidemiology and biology
      of C. trachomatis is considered.

PMID- 14692676
TI  - Blinding trachoma: prevention with the safe strategy.
AB  - Trachoma, the second leading cause of blindness worldwide, differentially affects
      the poorest communities, which may have the least access to resources. With the
      establishment of the Global Elimination of Blinding Trachoma by 2020 (GET 2020)
      goal, the World Health Organization has set an ambitious target for country
      programs. The currently recommended surgery for trichiasis/entropion, antibiotics
      for active disease, facial cleanliness, and environmental change to reduce
      transmission (SAFE) strategy targets all key elements believed to be necessary
      for a short- and long-term intervention program. This report reviews the need for
      a multi-faceted strategy, and the evidence supporting the elements of SAFE.
      Concerns about the implementation are discussed. Additional research is suggested
      that will enhance the implementation of the SAFE strategy. In the current climate
      of significant political and social momentum for trachoma control, the SAFE
      strategy is a safe bet to accomplish the elimination of blinding trachoma.

PMID- 14692677
TI  - The global elimination of blinding trachoma: progress and promise.
AB  - Trachoma is the world's leading cause of preventable blindness. It affects
      approximately 150 million people living in the world's poorest, rural communities
      and causes an estimated loss of $2.9 billion in productivity annually. In 1985,
      the Edna McConnell Clark Foundation joined with the World Health Organization to
      support studies on trachoma epidemiology and control, resulting in the
      elaboration of the surgery, antibiotics, facial cleanliness and environmental
      improvement (SAFE) strategy as the basis for the elimination of this blinding
      disease. Founded in 1998 by the Clark Foundation and Pfizer, Inc., the
      International Trachoma Initiative (ITI) is the only organization dedicated to
      eliminating blinding trachoma through support to national control programs. The
      availability of donated Zithromax (azithromycin) by Pfizer, Inc. has been
      paramount to the support of the ITI for implementation of SAFE in 10 country
      programs. The program has made considerable progress in four years. More than
      seven million individuals have received treatment, resulting in a cumulative
      reduction of 50% in active disease rates in children. More than 60,000 have also
      benefited from lid surgery that has halted progression to blindness. Morocco is
      expecting to attain the elimination of blinding trachoma by 2005. However, the
      challenges facing the goal of global elimination by 2020 involve a vital program
      expansion, increased financial and technical support, environmental improvement,
      and continued advocacy efforts.

PMID- 14692678
TI  - Integration of trachoma control into primary health care: the Tanzanian
      experience.
AB  - Tanzania was among the first countries to launch a trachoma control program with
      support from the International Trachoma Initiative (ITI) using surgery,
      antibiotics, facial cleanliness, and environmental improvement (SAFE) strategy
      with azithromycin. More than one million children less than 10 years of age in
      Tanzania have active disease and an estimated 54,000 people have trichiasis.
      Since 2000, Tanzania has implemented major health sector reform that have been
      carried out in three phases in 114 districts. A key aspect of the reform process
      is the policy of developing locally distributed essential health packages that
      then serve as the basis of the comprehensive council health plan. In 2002, the
      Tanzania Ministry of Health in collaboration with the ITI, the World Bank, and
      the office of the President embarked on a program of information for districts
      where trachoma is endemic but where no control program has been launched. Clear
      goals for the trachoma control program have been reviewed and discussed by the
      districts and as a result trachoma control was integrated into the comprehensive
      council health plans for 2003. This is expected to expand in 2004 and 2005. This
      work is presented as a model for the support and integration of disease-specific
      control efforts into the primary health care system.

PMID- 14692679
TI  - Trachoma: looking forward to Global Elimination of Trachoma by 2020 (GET 2020).
AB  - There is fortunately increasing international awareness of the problem of
      needless blindness from trachoma and enhanced international cooperation. This is
      exemplified by the World Health Organization Alliance for the Global Elimination
      of Blinding Trachoma by 2020 (GET 2020), the World Health Assembly resolution
      51.11, 1998, and the inclusion of trachoma as a priority under the disease
      control component of the Global Initiative for the Elimination of Avoidable
      Blindness, Vision 2020--the Right to Sight. Evidence-based advances in knowledge
      and intervention strategies together with the additional financial resources now
      available offer opportunities for a concerted effort to control and eliminate
      blinding trachoma, long before the year 2020, in most countries.

PMID- 14692680
TI  - The thrombospondin type 1 repeat (TSR) and neuronal differentiation: roles of SCO
      spondin oligopeptides on neuronal cell types and cell lines.
AB  - SCO-spondin is a large glycoprotein secreted by ependymal cells of the
      subcommissural organ. It shares functional domains called thrombospondin type 1
      repeats (TSRs) with a number of developmental proteins expressed in the central
      nervous system, and involved in axonal pathfinding. Also, SCO-spondin is highly
      conserved in the chordate phylum and its multiple domain organization is probably
      a chordate innovation. The putative involvement of SCO-spondin in neuron/glia
      interaction in the course of development is assessed in various cell culture
      systems. SCO-spondin interferes with several developmental processes, including
      neuronal survival, neurite extension, neuronal aggregation, and fasciculation.
      The TSR motifs, and especially the WSGWSSCSVSCG sequence, are most important in
      these neuronal responses. Integrins and growth factor receptors may cooperate as
      integrative signals. We discuss the putative involvement of the subcommissural
      organ/Reissner's fiber complex in developmental events, as a particular
      extracellular signaling system.

PMID- 14692681
TI  - Transendothelial transport and migration in vessels of the apparatus lymphaticus
      periphericus absorbens (ALPA).
AB  - The vessel of the apparatus lymphaticus periphericus absorbens (ALPA) represents
      the sector with high absorption capacity of the canalization of the lymphatic
      vascular system. It plays a basic role in preserving tissue homeostasis and in
      directing interstitial capillary filtrate back to the bloodstream. ALPA lymphatic
      endothelium differs from the endothelia of conduction and flowing vessels
      (precollectors, prelymph nodal and postlymph nodal collectors, main trunks),
      since it presents a discontinuous basement membrane, which is often absent, and
      lacks pores and fenestrations. The mesenchymal origin of the ALPA lymphatic
      vessel, morphological and ultrastructural aspects, intrinsic contractile
      properties, the presence of valves, innervation, and specific lymphatic markers
      that reliably distinguish it from blood capillaries are studied. Furthermore, its
      role in lymph formation through different mechanisms (hydrostatic pressure and
      colloidal osmotic-reticular mechanisms, vesicular pathway, and intraendothelial
      channel) is investigated. We have studied morphological and biomolecular
      mechanisms that control the transendothelial migration, from the extracellular
      interstitial matrix into the lumen of the lymphatic vessel, of cells involved in
      immune response and resistance (lymphocyte recirculation, etc.) and in the
      tumoral metastatic process via the lymphatic system. Finally, future research
      prospects, clinical implications, and therapeutic strategies are considered.

PMID- 14692682
TI  - Survey of the adrenal homolog in teleosts.
AB  - The adrenal homolog of teleosts is not a compact organ as the adrenal glands of
      most vertebrates but is composed by aminergic chromaffin and interrenal
      steroidogenic cells located mostly inside the head kidney that, in this taxon,
      generally has a hematopoietic function. The two tissues can be mixed, adjacent,
      or completely separated and line the endothelium of the venous vessels or are
      located in close proximity. The chromaffin cells in some species are also present
      in the posterior kidney. Histological and ultrastructural work revealed
      cytological peculiarities of both types of cells as compared to those of other
      vertebrate species. In particular, the interrenal ones can show some variations
      in ultrastructure depending on sex, time of the year, and relation to stress
      events. A periodic renewal of the whole gland tissue is also sustained by some
      studies. Research regarding development is scanty as compared to mammals and most
      studies go back to the early years of the past century. The adrenal homolog of
      teleosts is under hormonal and neuronal control. Moreover, local paracrine
      interactions may play an important role in modulating a system involved in stress
      response and osmoregulation. Most previous studies involved a few species with
      the object of intensive rearing for commercial purposes; in fact cortisol, the
      main hormone secreted by the interrenal cells, can also influence reproduction
      and growth. This review summarizes data from morphocytological work and refers to
      other excellent reviews regarding physiology. Some of the results are compared to
      data available from other fishes and vertebrate classes with the aim of including
      them in an evolutionary and environmental framework.

PMID- 14692683
TI  - G protein-coupled receptors in invertebrates: a state of the art.
AB  - G protein-coupled receptors (GPCRs) constitute one of the largest and most
      ancient superfamilies of membrane-spanning proteins. We focus on neuropeptide
      GPCRs, in particular on those of invertebrates. In general, such receptors
      mediate the responses of signaling molecules that constitute the highest
      hierarchical position in the regulation of physiological processes. Until
      recently, only a few of these receptors were identified in invertebrates.
      However, the availability of a plethora of genomic information has boosted the
      discovery of novel members in several invertebrate species, such as Drosophila,
      in which 18 neuropeptide GPCRs have been characterized. The finalization of
      genomic projects in other invertebrates will lead to a similar expansion of GPCR
      understanding. Many new insights regarding neuropeptide regulation have followed
      from the discovery of their cognate receptors. Furthermore, information on GPCR
      signaling is still fragmentary and the elucidation of these pathways in model
      insects such as Drosophila will lead to further insights in other species,
      including mammals. In this review we present the current status of what is known
      about invertebrate GPCRs, discuss some novel perceptions that follow from the
      identified members, and, finally, present some future prospects.

PMID- 14692684
TI  - Up-regulation of glial fibrillary acidic protein in response to retinal injury:
      its potential role in glial remodeling and a comparison to vimentin expression.
AB  - Intermediate filament proteins are a heterogeneous group of proteins that form 10
      nm-diameter filaments, a highly stable cytoskeletal component occurring in
      various cell types. The up-regulation of one of these intermediate filament
      proteins, glial fibrillary acidic protein (GFAP), historically has been an
      indicator of "stress" in central nervous system (CNS) astrocytes. The retina also
      responds similarly to "stress" but the up-regulation of intermediate filaments
      occurs primarily in the Muller cells, the radial glia of the retina. This is a
      remarkably ubiquitous response in that a similar up-regulation can be observed in
      numerous forms of retinal degeneration. As a consequence of retinal detachment, a
      "mechanical" injury to the retina, GFAP, and another intermediate filament
      protein, vimentin, dramatically increase in Muller cells. Concomitant with this
      up-regulation is the hypertrophy of these cells both within the retina and onto
      the photoreceptor and vitreal surfaces of the retina. The function of this
      distinctive intermediate filament up-regulation in glial cells is unknown, but in
      the retina their expression is differentially regulated in a polarized manner as
      the Muller cells hypertrophy, suggesting that they play some role in this
      process. Moreover the response of intermediate filaments and the Muller cells
      differs depending on whether the retina has been detached or reattached to the
      retinal pigment epithelium. The differential expression of these proteins may
      give insight into their role in the formation of glial scars in the retina and
      elsewhere in the CNS.

PMID- 14692685
TI  - Synovial membrane in the temporomandibular joint--its morphology, function and
      development.
AB  - This paper reviews recent findings of the synovial membrane, in particular the
      morphology, function and development of synovial lining cells, in the
      temporomandibular joint (TMJ). Electron microscopic studies have confirmed the
      synovial membrane in TMJ consists of macrophage-like type A cells and fibroblast
      like type B cells identical to those in other systematic joints. The macrophage
      like type A cells react with anti-macrophage and macrophage-derived substances
      including the major histocompatibility class II molecule, and show a drastic
      increase in their number in the inflamed synovial membrane. In addition, they
      have the ability to produce substances involved in the progression of TMJ
      inflammation such as nitric oxide and inducible nitric oxide synthase.
      Observation of osteopetrotic mice revealed that macrophage-like type A cells in
      TMJ are derived from monocyte lineage. Immunocytochemistry for 25kDa heat shock
      protein was able to depict the entire shape of fibroblast-like type B cells
      including their unique processes. The expression of an estrogen receptor alpha
      immunoreaction in the fibroblast-like type B cells may explain the etiology of
      temporomandibular disorders at a higher frequency in females than in males,
      suggesting that TMJ is a target tissue for estrogen. Furthermore, fibroblast-like
      type B cells are equipped with a basement membrane to serve as an adhesion
      molecule for the fibroblast-like type B cells to keep their epithelial
      arrangement. A clear understanding of the morphology of the intact synovial
      membrane will serve to clarify the etiology and development of temporomandibular
      disorders.

PMID- 14692686
TI  - Immunolocalization of the water channel, aquaporin-5 (AQP5), in the rat digestive
      system.
AB  - Aquaporin-5 (AQP5), an isoform of membrane water channel aquaporins, is expressed
      in the salivary and lacrimal glands. We surveyed the expression and
      immunohistochemical localization of AQP5 in the rat digestive system. RT-PCR
      analysis revealed that AQP5 is expressed in the submandibular gland, tongue,
      gastric corpus, pyloric region, duodenum, and liver. Immunofluorescence
      microscopy using AQP5-specific antibodies showed that AQP5 protein is present in
      the minor salivary glands of the tongue, the pyloric glands, and duodenal glands.
      To distinguish apical and basolateral domains of the plasma membrane of
      epithelial cells, double-immunofluorescence staining for AQP5 and tight junction
      protein occludin was performed. In the minor salivary gland, AQP5 was present in
      both the serous and mixed secretory end portions. AQP5 was found in the apical
      membrane of the secretory cells including intercellular secretory canaliculi
      demarcated with occludin. At higher magnifications, omega-shaped indentations of
      AQP5 labeling were seen along the apical membrane, suggesting a dynamic process
      for the apical membrane in exocytosis. Only weak labeling for AQP5 was detected
      in the basolateral domain. In the stomach, AQP5 was detected in the apical
      membrane of the pyloric gland secretory cells. In the duodenum, AQP5 was
      restricted to duodenal glands, where it was localized to the apical membrane.
      AQP5 was not detected in the intestinal glands or cells in the villi. These
      observations show that AQP5 is localized mainly in the apical membrane, including
      intercellular secretory canaliculi of secretory cells in the minor salivary
      glands, pyloric glands, and duodenal glands. AQP5 appears to play an important
      role in water transfer in these glands.

PMID- 14692687
TI  - Origins and pathways of fluid entering sublobular lymphatic vessels in cat
      livers.
AB  - The liver, which produces a large volume of lymph, has a lymphatic system which
      can be classified into three categories: portal, sublobular, and superficial
      lymphatic vessels. As little is known about the origin and pathways of sublobular
      lymph, this study demonstrates pathways of interstitial fluid flowing into
      sublobular lymphatic vessels. Livers from cats whose thoracic ducts were either
      ligated or non-ligated were examined by light-, transmission electron- and
      scanning electron-microscopy (SEM). Complete ligation of the thoracic duct caused
      significant dilation of the hepatic sinusoids, the space of Disse, and channels
      passing through the limiting plate. Sublobular interstitial space and sublobular
      lymphatic vessels were also expanded. The channels between hepatocytes forming
      the limiting plate contained collagen fibers, and connected the space of Disse
      with a sublobular interstitial space. The alkali-water maceration/SEM confirmed
      that collagen fibers traversing the layer of the limiting plate independently of
      blood vessels connected collagen fibers in the space of Disse with those in the
      sublobular space. Complete ligation of the thoracic duct also showed an
      accumulation of mast cells and plasma cells in the sublobular interstitial space.
      Our data suggest that fluid in the space of Disse flows along collagen fibers in
      channels traversing the limiting plate as well as those along the sinusoids and
      central veins that drain into sublobular veins, and enters the sublobular
      interstitial space to finally lead into sublobular lymphatic vessels. Our study
      has also shown that hepatic lymphostasis causes the accumulation of mast cells
      and plasma cells in the sublobular interstitial space, which may be involved in
      lymphangiogenesis and fibrogenesis.

PMID- 14692688
TI  - Ontogeny of plasma cells in the early rat yolk sac.
AB  - The present study investigated the development of plasma cells in the early rat
      yolk sac (days 10-16 of gestation) by light microscopy, transmission electron
      microscopy, immunoelectron microscopy, and indirect immunofluoresce techniques.
      Cells delineating the morphology of plasma cells in the yolk sac were observed as
      early as 12 days of embryonic life. As for positive immune staining for the intra
      cytoplasmic immunoglobulin (Ig) production (IgA, IgM and IgG), the intensity of
      the immune staining was very weak on days 10 and 11 of gestation, while it turned
      very dense on day 12 of gestation. At 14 days of gestation, the number of
      positive cells was markedly reduced. Immunoelectron microscopy visualized
      products of the immune reaction in cisterns of the rough endoplasmic reticulum.
      Conventional electron microscopic examination of 12, 13, and 16-day yolk sacs
      confirmed the development and differentiation of plasma cells with their well
      known ultrastructural features, making this the first study to demonstrate these
      in the early rat yolk sac. The development of plasma cells in the early yolk sac
      implies the ability of the yolk sac to effect a humoral immune response at this
      stage of fetal life. The probable role of plasma cells in the yolk sac is also
      discussed.

PMID- 14692689
TI  - Expression of gastrin-releasing peptide (GRP) in the bovine uterus during the
      estrous cycle.
AB  - Gastrin-releasing peptide (GRP) has been proposed as a novel regulatory peptide
      in the reproductive tract. We previously demonstrated that GRP immunoreactivities
      are found predominantly in the uterine gland epithelial cells of nonpregnant and
      pregnant cows. The present study focused on the distribution of GRP
      immunoreactivity and the expression of GRP mRNA in the bovine endometrium during
      the estrous cycle. Tissues were collected from 21 uterine horns and bodies during
      the estrous cycle. RT-PCR showed the expected GRP mRNA fragments (284 bp) in the
      tissues from all stages of the cycle. In situ hybridization results ascertained
      the expression of the GRP mRNA in the uterine gland epithelial cells and
      superficial epithelial cells of the endometrium. Positive staining of GRP
      immunoreactivity in the uterine gland epithelial cells was detected in both the
      uterine horn and body from all stages of the cycle. In metestrus and diestrus
      stages, GRP was also detected in the superficial epithelial cells of horn, but
      not in the body. The degrees of GRP mRNA expression and intensities of GRP
      immunoreactivity in the endometrium increased from proestrus to diestrus stages.
      These findings suggest that GRP may be important both in the endometrial
      remodeling during the estrous cycle and in the implantation and development of
      blastocysts.

PMID- 14692690
TI  - The expression of pancreatic endocrine markers in centroacinar cells of the
      normal and regenerating rat pancreas: their possible transformation to endocrine
      cells.
AB  - To determine the progenitor nature of centroacinar cells (CACs), we attempted to
      compare the expression pattern of endocrine cell markers and PDX-1 (pancreatic
      duodenal homeobox gene 1) in CACs of both the quiescent and the regenerating rat
      pancreas. In the normal pancreas, most CACs were relatively small cells with
      sparse cytoplasm and oval or elongated nuclei. In addition, we noticed a distinct
      population of a small number of large cells with round nuclei in the centroacinar
      region. By immunohistochemistry, 0.21% and 0.3% of CACs in normal rat pancreas
      were respectively found positive for glucagon and insulin, being large CACs and
      designated as GL-CAC and IL-CAC. They also exhibited the mRNA of each hormone by
      in situ hybridization (ISH). The ISH signal for glucagon but not insulin was also
      detected in a subset of small CACs (designated GS-CAC). The expression of PDX-1
      was also observed in subsets of small and large CACs (PS-CAC and PL-CAC,
      respectively). After a 90% pancreatectomy, the relative frequency for GS-CACs,
      but not those for other CACs, was significantly reduced in two days after
      surgery. On day 7 after surgery, the number of GS-CACs recovered to preoperative
      levels, whereas GL-CACs, IL-CACs, PS-CAC, and PL-CAC gradually increased to about
      double in number. From these results, a portion of CACs was suggested to
      differentiated into endocrine cells. A possible cell lineage is discussed for
      endocrine neogenesis during pancreatic regeneration.

PMID- 14692691
TI  - Tyramide signal amplification enhances the detectable distribution of connexin-43
      positive gap junctions across the ventricular wall of the rabbit heart.
AB  - Previous mapping studies examinig the distribution and pattern of staining for
      connexin-43 expression (the major ventricular gap junction protein) across the
      ventricular wall have yielded variable findings. The aim of this study was to
      determine if variations in the distribution of connexin-43 were due to
      histochemical detection problems, i.e. cross-linking of antigenic sites as a
      consequence of aldehyde fixation and/or due to low levels of protein expression
      within the epicardial or endocardial regions of the heart. Immunoperoxidase
      staining of connexin-43 using the ABC method was carried out in crosssections of
      rabbit hearts at the level of the papillary muscle. The following treatments were
      examined: the antibody (Ab) only, Ab with 1/2 Tyramide Signal Amplification (TSA)
      or full TSA; antibody with microwave antigen retrieval (AR); Ab + 1/2 TSA + AR
      and finally Ab + TSA + AR. Under light microscopy and using computerized image
      analysis the percentages of ventricular cross-sectional transmural staining for
      the different treatment groups were calculated: Ab amounted to only 55%; Ab + 1/2
      TSA 63%; Ab + TSA 78%; Ab + AR 72%; Ab + AR + 1/2 TSA 72% and Ab + AR + TSA 88%.
      The percentages of transumural connexin-43 staining in both TSA + Ab and Ab + TSA
      + AR groups when compared to Ab only were significantly greater p < 0.01. The
      antigenic cross-linking due to aldehyde fixation and low levels expression of
      connexin-43 are contributing factors that influence the immunohistochemical
      detection of connexin-43 in the mammalian heart. Methodological enhancement for
      the detection of connexin-43 in this study was derived primarily from
      amplification of low background levels of connexin-43 being expressed using the
      TSA protocol. This is supported by the significant differences encountered when
      TSA was utilized in the protocol and compared with antibody treatment only.

PMID- 14692692
TI  - Purification, cDNA cloning, and secretory properties of FLRG protein from PC12
      cells and the distribution of FLRG mRNA and protein in rat tissues.
AB  - A 35 kD protein was isolated and purified from conditioned media of Bcl-2 cDNA
      transfected PC12 cells and its cDNA cloned. A database analysis showed that the
      35 kD protein is a rat homologue of the human FLRG protein. The biochemical as
      well as morphological properties of the rat FLRG protein in PC12 cells were
      examined and its distribution in rat tissues determined. The levels of FLRG mRNA
      expressed were low during the fetal period, compared with those of follistatin
      mRNA. The distribution of FLRG and follistatin mRNAs differed from each other
      after birth; the expression levels of FLRG mRNA were abundant in the adrenal
      gland and testis, whereas those of follistatin mRNA and activin A were markedly
      high in the ovary. The presence of FLRG mRNA and/or protein was confirmed in
      spermatocytes at various differentiating stages andin endocrine cells of both the
      adrenal cortex and medulla. When overexpressed in PC12 cells, the FLRG protein
      was found to be stored in secretory granules of the cells and largely secreted by
      a regulated pathway, while activin A enhancedthe constitutive secretion of the
      FLRG protein from wild-typpe PC12 cells, indicating that the FLRG protein
      possesses dualproperties in secretory pathways. The different distribution
      between FLRG and follistatin mRNA suggests that, like follistatin in the ovary,
      the FLRG protein may be involved in the maintenance of spermatogenesis in the
      testis and the growth and function of adrenal tissue cells, probably by
      regulating the functions of its binding partners such as the TGF-beta (
      superfamily members.

PMID- 14692693
TI  - Phosphodiesterases in the vascular system.
AB  - Cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'
      monophosphate (cGMP) are second messengers involved in the intracellular signal
      transduction of a variety of extracellular stimuli in several tissues. In the
      vascular system, these nucleotides play important roles in the regulation of
      vascular tone and in the maintenance of the mature contractile phenotype in
      smooth muscle cells. Given that cyclic nucleotide signaling regulates a wide
      variety of cellular functions, it is not surprising that cyclic nucleotide
      phosphodiesterases (PDEs). In paticular, the accumulating data showing that there
      are a large number of different PDE isozymes have triggered an equally large
      increase in interest about these enzymes. At least 11 different gene families of
      PDEs are currently known to exist in mammalian tissues. Most families contain
      several distinct genes, and many of these genes are expressed in different
      tissues as functionally unique alternative splice variants. This article reviews
      many of the important aspects about the structure, cellular localization, and
      regulation of each family of PDEs. Particular emphasis is placed on new
      information obtained in the last few years about vascular disease. The
      development of novel methods to deliver more potent and selective PDE inhibitors
      to individual cell types and subcellular locations will lead to new therapeutic
      uses for this class of drugs in diseases of the vascular system.

PMID- 14692694
TI  - Postprandial acid reflux is reduced by delayed gastric emptying.
AB  - The aim of this study was to investigate influence of delayed gastric emptying on
      postprandial reflux in esophageal pH. Sixty-nine consecutive patients underwent
      24 hour (h) esophageal pH monitoring and gastric emptying. In 24 h esophageal pH
      monitoring, % postprandial reflux pH<4 for 2 h after each meal (% PRT) was
      extracted from the 24 h pH profile. After solid test meal (1 mCi, Tc99m) was
      given, gastric emptying was measured with a gamma detector placed transnasally 5
      cm below lower esophageal sphincter. % PRT was similar among the 34 normal, 26
      delayed and 9 rapid gastric emptying rate patients. Thirty-five with a positive
      pH study and 34 with a negative had a similar prevalence of gastric emptying
      disorder. In the positive pH study group, patients with normal gastric emptying
      had significantly higher % PRT than those with delayed gastric emptying (22.0 vs
      12.1%, P<0.05). In the same population, patients with a normal %PRT had a
      significantly higher prevalence of delayed gastric emptying compared with those
      with a positive % PRT (6/8 vs 9/27, P<0.05). In patient with abnormal acid
      exposure but normal % PRT on 24 h esophageal pH monitoring, gastric emptying may
      be delayed.

PMID- 14692695
TI  - Intimal changes in the cephalic vein of renal failure patients before arterio
      venous fistula (AVF) construction.
AB  - Native cephalic vein remains the superior dialysis conduit, even thirty years
      after it was first described. However, up to 37% of hemodialysis patients develop
      progressive stenosis in the venous circuit of arterio-venous fistula (AVF), which
      may later cause thrombosis and occlusion. To study the pre-existing morphological
      changes in the wall of the cephalic vein before AVF construction, we collected 23
      cephalic vein specimens from 3 normal, young trauma and twenty renal failure
      patients. The samples were collected at the time of vascular repair in the first
      group and AVF construction in the second group. Sections were prepared and
      stained for both light and transmission electron microscopy (TEM) examination.
      Compared with normal cephalic vein, all pre-access cephalic veins showed
      thickening of the wall and intimal hyperplasia. Other changes were loss of
      internal elastic lamina in 9 (45%) patients, loss of endothelial cell layer in 6
      (30%), inflammatory cell infiltration of the wall in 5 (25%), mural calcification
      in 3 (15%) and telangiectasia in 2 (10%). Other ultrastructural changes observed
      were intimal hypertrophy, degeneration and loss of the endothelial cells,
      degeneration and fraying of smooth muscle cells (SMCs) and loss of wall
      components into the lumen. In conclusion, most of the apparently normal cephalic
      veins of renal failure patients showed morphological abnormalities at the time of
      AVF construction, which may well influence the outcome of shunts in terms of
      future stenosis and failure. It seems likely that the later development of AVF
      stenosis may be the result of pre-existing disease rather than the direct insult
      of arterialization.

PMID- 14692696
TI  - The molecular era of myology.
AB  - This review covers, in general terms, the salient features and impact of
      molecular myology under the following headings: its role in providing clues for
      the understanding of molecular etiology and pathogenesis of genetic myopathies,
      its contribution to the modernization and rationalization of the classification
      of muscle diseases, providing means of precise diagnosis and prevention of
      myopathies, development of radically new cell and gene therapies, and
      determination of future research directions. Myology appears to be among the
      medical disciplines that have benefited a great deal from molecular science. This
      remarkable progress will hopefully translate into effective treatment
      capabilities in the near future.

PMID- 14692697
TI  - Stable tubule only polypeptides (STOP) proteins co-aggregate with spheroid
      neurofilaments in amyotrophic lateral sclerosis.
AB  - A major cytopathological hallmark of amyotrophic lateral sclerosis (ALS) is the
      presence of axonal spheroids containing abnormally accumulated neurofilaments.
      The mechanism of their formation, their contribution to the disease, and the
      possibility of other co-aggregated components are still enigmatic. Here we
      analyze the composition of such lesions with special reference to stable tubule
      only polypeptide (STOP), a protein responsible for microtubule cold
      stabilization. In normal human brain and spinal cord, the distribution of STOP
      proteins is uniform between the cytoplasm and neurites of neurons. However, all
      the neurofilament-rich spheroids present in the tissues of affected patients are
      intensely labeled with 3 different anti-STOP antibodies. Moreover, when
      neurofilaments and microtubules are isolated from spinal cord and brain, STOP
      proteins are systematically co-purified with neurofilaments. By SDS-PAGE
      analysis, no alteration of the migration profile of STOP proteins is observed in
      pathological samples. Other microtubular proteins, like tubulin or kinesin, are
      inconstantly present in spheroids, suggesting that a microtubule destabilizing
      process may be involved in the pathogenesis of ALS. These results indicate that
      the selective co-aggregation of neurofilament and STOP proteins represent a new
      cytopathological marker for spheroids.

PMID- 14692698
TI  - Environmental enrichment exacerbates amyloid plaque formation in a transgenic
      mouse model of Alzheimer disease.
AB  - Epidemiological studies of Alzheimer patients from a wide variety of ethnic and
      socioeconomic backgrounds have identified education and occupation as
      environmental factors that can affect the risk of developing disease. A model of
      environmental manipulation in rodents uses enriched housing to provide cognitive
      and social stimulation. Previous studies have established elevations in synaptic
      number and function in rodents housed under enriched conditions. Recent
      experiments in hippocampal cultures have demonstrated that synaptic activity can
      influence the processing of amyloid precursor protein (APP). Here we examined
      whether changes in synaptic activity brought about by enriched housing might also
      influence the deposition of amyloid plaques in vivo using a transgenic mouse
      model of Alzheimer disease (AD). Mice co-expressing mutant APP and presenilin 1
      (PS1) were housed in either enriched or standard cages from 2 months of age and
      then killed for pathological evaluation several months later. We find that, as
      compared to littermates housed in standard cages, the enriched APP/PS1 transgenic
      mice develop a higher amyloid burden with commensurate increases in aggregated
      and total A beta. These results suggest that A beta deposition can be exacerbated
      by the neuronal changes associated with enrichment, and demonstrate a
      substantial, albeit paradoxical, environmental influence on the progression of
      pathology in a mouse model of AD.

PMID- 14692699
TI  - Neurochemical mechanisms induced by high frequency stimulation of the subthalamic
      nucleus: increase of extracellular striatal glutamate and GABA in normal and
      hemiparkinsonian rats.
AB  - High frequency stimulation (HFS) (130 Hz) of the subthalamic nucleus (STN)
      provides beneficial effects in patients suffering from severe parkinsonism, but
      the mechanisms underlying these clinical results remain to be clarified. To date,
      very little is known concerning the effects of STN-HFS on neurochemical
      transmission in the different basal ganglia nuclei and in particular the
      striatum. This study examines the effects of STN-HFS in intact and
      hemiparkinsonian rats on extracellular striatal glutamate (Glu) and GABA levels
      by means of intracerebral microdialysis. Unilateral STN-HFS was found to induce a
      significant bilateral increase of striatal Glu and GABA both in intact and in
      dopamine-lesioned animals. In intact rats, these increases were reversed by local
      administration of the D1 antagonist SCH 23390, but were potentiated by the D2
      antagonist sulpiride. Potentiation was also observed after local administration
      of both D1 and D2 antagonists whose amplitude was similar to that measured in
      hemiparkinsonian rats. These data furnish the first evidence that STN-HFS
      influences striatal amino-acid transmission and that this influence is modulated
      by dopamine. They provide evidence that the effects of STN-HFS are not only
      restricted to the direct STN targets, but also involve adaptive changes within
      other structures of the basal ganglia circuitry.

PMID- 14692700
TI  - Morphogenesis of Lewy bodies: dissimilar incorporation of alpha-synuclein,
      ubiquitin, and p62.
AB  - The formation of Lewy bodies (LBs) and their relationship to other types of
      nigral inclusions associated with Parkinson disease (PD), such as pale bodies
      (PBs), remain poorly understood. Known constituents of LBs include alpha
      synuclein (alphaS) and ubiquitin (Ub), providing windows to their morphogenesis.
      Additionally, p62/sequestosome 1 has been identified as a common component of
      neuropathological and hepatocytic inclusions. To study the formation of PD
      associated nigral inclusions, we analyzed the substantia nigra of cases with
      abundant LBs and PBs in hematoxylin and eosin (H&E) stain, using
      immunohistochemistry for alphaS, Ub, and p62. We found morphologically diverse
      alphaS-immunoreactive deposits within neuronal perikarya and neurites. Perikaryal
      types extended from punctate cytoplasmic staining to variform compact (i.e. PB
      type and LB-type) inclusions. Using H&E, only a small subset of the compact
      deposits could be unambiguously identified. Labeling for p62 was highly similar
      to alphaS in compact perikaryal inclusions, whereas no punctate staining or
      intraneuritic inclusions were detected. Ubiquitin antibodies labeled compact
      deposits both within perikarya and neurites. The data suggest that pathological
      alphaS is first evident as punctate perikaryal material that, via coalescence and
      incorporation of p62 and Ub, yields PB-type structures from which LB-type
      inclusions form in a compaction-like manner. The results also point at
      dissimilarities in the formation of perikaryal vs intraneuritic inclusions.

PMID- 14692701
TI  - Pro-inflammatory cytokines modulate matrix metalloproteinase secretion and
      organic anion transport at the blood-cerebrospinal fluid barrier.
AB  - Neuroinflammation and neuroinfection trigger cytokine-mediated responses that
      include an increase in the cerebrospinal fluid (CSF) levels of pro-inflammatory
      matrix metalloproteinases (MMPs) and organic anions such as leukotrienes and
      prostaglandins. The choroid plexus (CP) epithelium forming the interface between
      the blood and the CSF regulates the CSF concentration of bioactive organic anions
      and is involved in neuro-immune regulation. We demonstrated that both fourth and
      lateral ventricle CPs are a source of pro- and active MMP-2 and MMP-9 in the
      brain. Using a cellular model of the blood-CSF barrier, we showed that a pro
      inflammatory cytokine treatment leads to an increase in the choroidal MMP
      secretion at either the apical or the basolateral membrane, depending on the
      ventricular origin of the choroidal cells. This effect was not concomitant with
      an alteration in the structural blood-CSF barrier. Neither was the pool of
      antioxidant sulfhydryls in the choroidal cells challenged. In contrast, the
      efficiency of the choroidal epithelium to clear the CSF from organic anions was
      highly reduced. Thus, during inflammation, the CPs could be one source of MMPs
      found in the CSF facilitate leucocyte migration by secreting MMPs into the
      choroidal stroma, and promote the inflammatory process by failing in its ability
      to clear deleterious compounds from the brain.

PMID- 14692702
TI  - Expression and function of the receptor protein tyrosine phosphatase zeta and its
      ligand pleiotrophin in human astrocytomas.
AB  - Using subtractive cloning combined with cDNA array analysis, we previously
      identified the genes encoding for the protein tyrosine phosphatase zeta/receptor
      type protein tyrosine phosphatase beta (PTPzeta/RPTPbeta) and its ligand
      pleiotrophin (PTN) as overexpressed in human glioblastomas compared to normal
      brain. Both molecules have been implicated in neuronal migration during central
      nervous system development, and PTN is known to be involved in tumor growth and
      angiogenesis. We confirm overexpression of both molecules at the protein level in
      astrocytic gliomas of different malignancy grades. PTPzeta/RPTPbeta
      immunoreactivity was associated with increasing malignancy grade and localized
      predominantly to the tumor cells. PTN immunoreactivity as determined by ELISA and
      immunohistochemistry analysis was increased in low-grade astrocytomas compared to
      normal brain. Further increase in malignant gliomas was marginal, and thus no
      correlation with malignancy grade or microvessel density was present. However,
      PTN levels were significantly associated with those of fibroblast growth factor
      2, suggesting co-regulation of both factors. Functionally, PTN induced weak
      chemotactic and strong haptotactic migration of glioblastoma and cerebral
      microvascular endothelial cells. Haptotaxis of glioblastoma cells towards PTN was
      specifically inhibited by an anti-PTPzeta/RPTPbeta antibody. Our findings suggest
      that upregulated expression of PTN and PTPzeta/RPTPbeta in human astrocytic tumor
      cells can create an autocrine loop that is important for glioma cell migration.
      Although PTN is a secreted growth factor, it appears to exert its mitogenic
      effects mostly in a matrix-immobilized form, serving as a substrate for migrating
      tumor cells.

PMID- 14692703
TI  - Focal lesions in the rat central nervous system induced by endothelin-1.
AB  - Axon injury following cerebral ischemia has received little scientific attention
      compared to the abundance of information dealing with the pathophysiology of grey
      matter ischemia. There are differences in the initial response of grey and white
      matter to ischemia in vitro. In this study we investigate whether the vasoactive
      peptide, endothelin-1, can generate a focal ischemic lesion in the white matter
      and compare the findings with endothelin-1-induced lesions in the grey matter.
      Using a minimally invasive technique to microinject endothelin-1 into selected
      brain regions, we observed an acute reduction in local MRI perfusion in the
      injected hemisphere after 1 hour. Twenty-four hours after microinjection of 10
      pmoles of endothelin-1, we observed a loss of neurons in the grey matter. At 72
      hours, neutrophils were absent and a macrophage/microglia response and astrocyte
      gliosis were detected. No breakdown in the blood-brain barrier was detected.
      After injection of 10 pmoles endothelin-1 into the cortical white matter, we
      observed prolific amyloid precursor protein-positive immunostaining (indicative
      of axonal disruption) and an increase in tau-1 immunostaining in oligodendrocytes
      at 6 hours. Similar to the grey matter lesions, no neutrophils were present, a
      macrophage/microglia response did not occur until 72 hours and there was no
      disruption in the blood-brain barrier. Focal injections of endothelin-1 into
      specific areas of the rat CNS represent a model to investigate therapeutic
      approaches to white matter ischemia.

PMID- 14692704
TI  - Vascular pathology in Alzheimer disease: correlation of cerebral amyloid
      angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline.
AB  - Sporadic, late-onset Alzheimer disease (AD) constitutes the most frequent cause
      of dementia in the elderly population. AD-related pathology is often accompanied
      by vascular changes. The predominant vascular lesions in AD are cerebral amyloid
      angiopathy (CAA) and arteriosclerosis/lipohyalinosis (AS/LH). The present study
      was carried out to examine the coincidence of these small vessel pathologies
      during the development of cognitive deficits, amyloid beta-protein (A beta)
      deposition, and neurofibrillary tangle (NFT) formation in sporadic late-onset AD.
      We correlated the clinical dementia rating (CDR) score, the sequential extension
      of AD-related A beta deposition into different parts of the brain, and the
      extension of NFTs to involve more brain regions with the distribution of CAA and
      AS/LH in 52 human autopsy brains. The extension of CAA and AS/LH to involve
      different areas of the brain was associated with a rise of CDR scores and an
      increase in the extension of A beta deposition and NFT generation. AD cases
      showed a higher number of regions with CAA and AS/LH compared to nondemented
      patients with AD-related pathology and controls. Moreover, we demonstrated a
      hierarchical sequence in which the different regions of the brain exhibited CAA
      and AS/LH-affected vessels, allowing the distinction of 3 stages in the
      development of CAA and AS/LH. The first stage of CAA involved leptomeningeal and
      neocortical vessels. The second stage was characterized by additional A beta
      deposition in allocortical and midbrain vessels. Finally, in a third stage, CAA
      was observed in the basal ganglia, the thalamus, and in the lower brainstem. In
      contrast, AS/LH initially affected the basal ganglia in stage A. In stage B this
      pathology made inroads into the deep white matter, the leptomeningeal arteries of
      the cortex, the cerebellum, and into the thalamus. Stage C was characterized by
      AS/LH in brainstem vessels. Our results demonstrate widespread CAA and AS/LH to
      be associated with the development of cognitive deficits in AD. A combination of
      both CAA and AS/LH may, therefore, contribute to neurodegeneration in AD. These
      data also suggest that small vessel disease due to arteriosclerosis and
      fibrolipohyalinosis is a potential target for the treatment of AD.

PMID- 14692705
TI  - AANP award for meritorious service presented to Bernardino Ghetti, MD.

PMID- 14692706
TI  - Use of statins in primary and secondary prevention of coronary heart disease and
      ischemic stroke. Meta-analysis of randomized trials.
AB  - OBJECTIVE: To estimate the relative risk reduction of the clinical outcomes
      (coronary events, strokes, cardiovascular, non-cardiovascular and all-cause
      mortality) associated with statin therapy in primary and secondary prevention.
      DATA SOURCES: A literature search of the Medline and Cohrane databases for
      articles published from 1985 to July 2002 was performed. The data on systematic
      reviews and preliminary reports were also included in this study. Primary and
      secondary prevention trials and regression trials were eligible. DATA EXTRACTION
      AND STATISTICAL METHOD: Data were extracted by 2 authors according to the defined
      inclusion criteria. Disagreements were resolved by consensus or by a third
      reviewer. Testing for heterogeneity was applied and on the basis of these results
      a fixed effect model or a random effect model was used for calculation of
      relative risk values (RR) and 95% confidence intervals (95% CI). Sensitivity
      analysis tested the impact of the individual study--duration of study, type of
      statin therapy and study size. The number of patients needed to treat was
      calculated as an absolute measure of clinical effectiveness of statin therapy
      when appropriate. RESULTS: Data from 15 trials with 63,410 participants and mean
      duration of treatment of 3.6 years, were included in this overview. Tests for
      heterogeneity showed that the variability between study estimates is sufficiently
      small to assume that they are estimating the same underlying treatment effect.
      Statin therapy was associated with a 22% reduction in total cholesterol, 29%
      reduction in LDL cholesterol, 12% reduction in triglycerides and 6% increase in
      HDL cholesterol. Overall (primary and secondary studies) statin therapy
      significantly reduces relative risk of coronary events (RR, 0.73, 95% CI, 0.68,
      0.77, *p < 0.0001), relative risk of cardiovascular disease mortality (RR, 0.78,
      95% CI, 0.73, 0.84, *p < 0.0001), relative risk of non-fatal stroke (RR, 0.74,
      95% CI, 0.67, 0.82, *p < 0.0001), relative risk of total (fatal and non-fatal)
      stroke (RR, 0.77, 95% CI, 0.70, 0.84, *p < 0.001) and relative risk of all-cause
      death (RR, 0.85, 95% CI, 0.81, 0.89, *p < 0.0001). There was a slight and
      insignificant reduction of relative risk in non-cardiovascular mortality (RR,
      0.94, 95% CI, 0.86, 1.03, p = 0.1677) and fatal strokes (RR, 0.86, 95% CI, 0.70,
      1.07, p = 0.1912). Sensitivity analysis showed the robustness of our results for
      all outcomes. The results were not altered if an individual study was removed
      from meta-analysis. CONCLUSIONS: This overview indicates that statin treatment
      reduces the relative risk of occurrence of coronary events, cardiovascular
      disease mortality, non-fatal strokes and all-cause mortality. While secondary
      prevention with statins provides considerable improvement of cardiovascular
      morbidity/mortality, primary prevention with statins provides only small and
      clinically hardly relevant improvement of cardiovascular morbidity/mortality.

PMID- 14692707
TI  - Serum carvedilol concentration and its relation to change in plasma brain
      natriuretic peptide level in the treatment of heart failure: a preliminary study.
AB  - OBJECTIVE: To examine the influence of carvedilol dose and concentration in serum
      on plasma brain natriuretic peptide (BNP), a measure of heart failure
      progression. METHODS: 12 patients with New York Heart Association (NYHA)
      functional class II-III chronic heart failure were enrolled in the study. They
      received carvedilol at daily doses of 1-20 mg with a 1-2 weekly adjustment. Serum
      carvedilol trough concentrations were measured in steady-state using a specific
      fluorescence HPLC method. The degree of improvement in heart failure was assessed
      from the ratio of change in the plasma BNP concentration, 2 weeks, 1 month and 3
      months after the commencement of carvedilol administration. RESULTS: From the
      pharmacokinetic aspect, there was no valid correlation between the trough serum
      carvedilol concentration (Cmin) and daily dose per body weight (Dd/BW),
      indicating that there was a wide difference in the carvedilol elimination
      capacity among individuals. A significant decrease in the BNP was observed at the
      3rd month in patients treated with the high dose (> 750 mg/3 months). On the
      other hand, in patients with a mean serum carvedilol level (Cmin) of less than
      2.5 nmol/l up to 2 weeks after the start ofcarvedilol therapy, the degree of
      reduction in the BNP value after the 3rd month was significantly larger, relative
      to the patient group with Cmin over 2.5 nmol/l. CONCLUSIONS: The total carvedilol
      dose was confirmed to be one of the determinants for improvement in heart
      failure, and it was suggested that the initial serum level also plays an
      important role in therapeutic outcome. Therefore, it may be important to monitor
      the serum carvedilol level at the introductory period to determine the daily dose
      requirements because of the wide inter-individual variability in its metabolic
      clearance.

PMID- 14692708
TI  - Vitamin E and its effect on arterial stiffness in postmenopausal women--a
      randomized controlled trial.
AB  - INTRODUCTION: Arterial stiffness is emerging as a useful index of vascular
      health. Postmenopausal women have been shown to have stiffer arteries. Hormone
      replacement therapy and soy isoflavones improve arterial stiffness in these
      women. The aim of this study is to establish whether vitamin E improves arterial
      stiffness in postmenopausal women after 10 weeks of supplementation. METHODS:
      Twenty postmenopausal women with a mean age of 54.59 +/- 1.22 years participated
      in this randomized, crossover, double-blind, placebo-controlled clinical trial.
      All women received 400 IU of tocopherol daily for 10 weeks or a placebo capsule,
      before being crossed over for treatment. At intervals of 5 weeks, subjects
      attended sessions where measurements of arterial stiffness, blood pressure and
      plasma vitamin E level were taken. Pulse wave velocity measurement, using the
      automated Complior machine, was used as an index of arterial stiffness. RESULTS:
      Plasma vitamin E level was 30.38 +/- 1.56 micromol/l at baseline, after treatment
      it was 59.01 +/- 3.30 micromol/l and 31.17 +/- 1.37 micromol/l with vitamin E and
      placebo, respectively (p < 0.001). There was no significant difference in pulse
      wave velocity after 10-week treatment with placebo and vitamin E (9.14 +/- 0.29
      versus 9.04 +/- 0.29 m/s, respectively). Similarly, no difference in systolic and
      diastolic blood pressure was seen between placebo and vitamin E at the end of 10
      weeks. CONCLUSION: Supplementary vitamin E for 10 weeks at 400 IU daily has no
      effect on arterial stiffness in healthy postmenopausal women.

PMID- 14692709
TI  - Comparative bioavailability of silibinin in healthy male volunteers.
AB  - AIM: To study a comparative bioavailability of Liverman capsule to Legaion
      capsule and Silymarin tablet (which contain silibinin) in 24 healthy volunteers.
      VOLUNTEERS AND METHODS: Twenty-four healthy male Korean volunteers received each
      medicine at the silibinin dose of 120 mg in a 3 x 3 crossover study. There was a
      1-week washout period among the doses. Plasma concentrations of silibinin were
      monitored by a high-performance liquid chromatography for over a period of 12
      hours after the administration. AUCinf (the area under the plasma concentration
      time curve from time zero to time infinity) was calculated by the trapezoidal
      rule extrapolation method. Cmax (maximum plasma drug concentration) and tmax
      (time to reach a Cmax) were compiled from the plasma concentration-time data.
      Analysis of variance was carried out using logarithmically transformed AUCinf,
      AUC(0-12h), and Cmax and untransformed tmax. RESULTS: After an oral
      administration of Liverman capsule, the pharmacokinetic parameters of silibinin,
      such as AUC(0-12h) (5.59, 4.24 and 13.9 microg/ml x h for Legalon capsule,
      Silymarin tablet and Liverman capsule, respectively) and AUCinf (6.00, 4.63 and
      15.1 microg/ml x h) were significantly greater, Cmax (1.33, 1.13 and 6.04
      microg/ml) was significantly higher and tmax (1.83, 2.10 and 0.875 h) was
      significantly faster than those after Legalon capsule and Silymarin tablet.
      CONCLUSION: These results indicate that the absorption and the extent of relative
      oral bioavailability of silibinin after Liverman capsule were significantly
      faster and greater, respectively, than those after Legalon capsule and Silymarin
      tablet.

PMID- 14692710
TI  - The influence of liver metastases on the pharmacokinetics of doxorubicin---a
      population-based pharmacokinetic project of the CESAR-APOH.

PMID- 14692711
TI  - Surrogate marker in clinical studies with anti-angiogenic drugs.

PMID- 14692712
TI  - DCE-MRI in clinical trials: data acquisition techniques and analysis methods.

PMID- 14692713
TI  - Cerebrospinal fluid pharmacokinetics after different dosage regimens of
      intraventricular etoposide.

PMID- 14692714
TI  - Two schedules of application for mesna and their influence on the thiol
      metabolism.

PMID- 14692715
TI  - The role of hepatic Mrp2 in the interaction of flavopiridol and bilirubin: impact
      on therapy.

PMID- 14692716
TI  - Assessment of platinum sensitivity in human tumor cells.

PMID- 14692717
TI  - Circadian rhythm in the regulation of the MAP kinase pathway--pitfall in the
      determination of surrogate parameters?

PMID- 14692718
TI  - Antitumor effect and potentiation or reduction in cytotoxic drug activity in
      human colon carcinoma cells by the Raf kinase inhibitor (RKI) BAY 43-9006.

PMID- 14692719
TI  - Drug-drug interaction pharmacokinetic study with the Raf kinase inhibitor (RKI)
      BAY 43-9006 administered in combination with irinotecan (CPT-11) in patients with
      solid tumors.

PMID- 14692720
TI  - A phase I clinical and pharmacokinetic study of the Raf kinase inhibitor (RKI)
      BAY 43-9006 administered in combination with doxorubicin in patients with solid
      tumors.

PMID- 14692721
TI  - Novel antitumoral compound isolated from Clusia rosea.

PMID- 14692722
TI  - Gene expression profiling of colon cancer reveals a broad molecular repertoire in
      5-fluorouracil resistance.

PMID- 14692723
TI  - Treatment of anxiety, tension and restlessness states with Kava special extract
      WS 1490 in general practice: a randomized placebo-controlled double-blind
      multicenter trial.
AB  - The efficacy and tolerability of 150 mg/d Kava special extract WS 1490 were
      investigated in a randomized, placebo-controlled, double-blind multicenter study
      in patients suffering from neurotic anxiety (DSM-III-R diagnoses 300.02, 300.22,
      300.23, 300.29, or 309.24). 141 adult, male and female out-patients received 3 x
      1 capsule of 50 mg/d WS 1490 or placebo for four weeks, followed by two weeks of
      observation without study-specific treatment. During randomized treatment the
      total score of the Anxiety Status Inventory (ASI) observer rating scale showed
      more pronounced decreases in the WS 1490 group than in the placebo group.
      Although a treatment group comparison of the post-treatment ASI scores was not
      significant (p > 0.05), an exploratory analysis of variance across the
      differences between treatment end and baseline, with center as a second factor,
      showed superiority of the herbal extract over placebo (p < 0.01, two-sided). 73%
      of the patients treated with WS 1490 exhibited ASI score decreases > 5 points
      versus baseline, compared to 56% for placebo. Significant advantages for WS 1490
      were also evident in a structured well-being self-rating scale (Bf-S) and the
      Clinical Global Impressions (CGI), while the Erlangen Anxiety, Tension and
      Aggression Scale (EAAS) and the Brief Test of Personality Structure (KEPS) showed
      only minor treatment group differences. Although the results show consistent
      advantages for WS 1490 over placebo in several psychiatric scales and indicate
      significant improvements in the patients' general well-being, the differences
      versus placebo were not as large as in previous trials which employed 300 mg/d of
      the same extract. WS 1490 was well tolerated, with no influence on liver function
      tests and only one trivial adverse event (tiredness) attributable to the study
      drug.

PMID- 14692724
TI  - Phytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): a
      medicinal plant with anxiolytic properties.
AB  - The phytochemistry and biological activity of Scutellaria lateriflora L.
      (American skullcap) which has been traditionally used as a sedative and to treat
      various nervous disorders such as anxiety was studied. In vivo animal behaviour
      trials were performed to test anxiolytic effects in rats orally administered S.
      laterifolia extracts. Significant increases in the number of entries into the
      center of an "open-field arena"; number of unprotected head dips, number of
      entries and the length of time spent on the open arms of the Elevated Plus-Maze
      were found. The identification and quantification of the flavonoid, baicalin in a
      50% EtOH extract (40 mg/g) and its aglycone baicalein in a 95% EtOH extract (33
      mg/g), as well as the amino acids GABA in H2O and EtOH extracts (approximately
      1.6 mg/g) and glutamine in a H2O extract (31 mg/g), was performed using HPLC.
      These compounds may play a role in anxiolytic activity since baicalin and
      baicalein are known to bind to the benzodiazepine site of the GABAA receptor and
      since GABA is the main inhibitory neurotransmitter.

PMID- 14692725
TI  - Inhibition of monoamine oxidase B (MAO-B) by Chinese herbal medicines.
AB  - Monoamine oxidase (MAO) catalyzes the oxidative deamination of biogenic amines
      accompaned by the release of H2O2. Two subtypes, MAO-A and MAO-B, exist on the
      basis of their specificities to substrates and inhibitors. The regulation of MAO
      B activity is important in the treatment of neurodegenerative diseases. Twenty
      seven species of plants used in traditional Chinese medicines, selected from an
      enthnobotanical survey, were used in an investigation of their inhibitory effect
      on MAO-B in rat brain homogenates. The 50% aqueous methanol extracts of four
      active extracts, Arisaema amurense, Lilium brownii var. colchesteri, Lycium
      chinense, and Uncaria rhynchophylla, exhibited the best activity and selectivity
      towards MAO-B with IC50 values of 0.44, 0.29, 0.40, and 0.03 mg/ml, respectively.
      A kinetic study of MAO-B inhibition by the four extracts using the Lineweaver
      Burk plot for each active extract revealed the IC50 concentrations, and results
      show that: Ki = 0.59 mg/ml for A. amurense for the mixed-type mode, Ki = 0.58
      mg/ml for L. brownii var. colchesteri for the mixed-type mode, Ki = 5.01 mg/ml
      for L. chinense for the uncompetitive mode, and Ki = 0.02 mg/ml for U.
      rhynchophylla for the uncompetitive mode. These may therefore be candidates for
      use in delaying the progressive degeneration caused by neurological diseases.

PMID- 14692726
TI  - Dietary intake of the flower extracts of German chamomile (Matricaria recutita
      L.) inhibited compound 48/80-induced itch-scratch responses in mice.
AB  - The antipruritic effects of the diets containing German chamomile on the compound
      48/80-induced scratching in ddY mice were examined. Since it is reported that an
      injection of compound 48/80, but not histamine, induced scratching behaviour due
      to itch but not to pain in ddY mice (Kuraishi et al., 1995), compound 48/80
      induced scratching in ddY mice seems to be a suitable parameter for evaluating
      antipruritic agents independent of histamine receptor antagonism. In the mice fed
      the diet containing 1.2 w/w % of the ethyl acetate extract of dried flower of
      German chamomile (Matricaria recutita L.) for 11 days, the compound 48/80-induced
      scratching behaviour was significantly suppressed. The ethyl acetate extract of
      German chamomile dose dependently suppressed compound 48/80-induced scratching
      without affecting body weight increase. The ethyl acetate fraction of the ethanol
      extract and the ethanol extract of hot water extraction residue of German
      chamomile flower also showed strong inhibition on the compound 48/80-induced
      scratching. The inhibitory effects of the dietary intake of the German chamomile
      extracts on compound 48/80-induced itch-scratch response were comparable to
      oxatomide (10 mg/kg, p.o.), an anti-allergic agent.

PMID- 14692727
TI  - The combined effects of Trigonella and Allium extracts in the regulation of
      hyperthyroidism in rats.
AB  - The combined effects of Trigonella foenum-graecum and Allium sativum extracts
      were evaluated for their ameliorative potential in the L-thyroxine-induced
      hyperthyroidic rat model to contribute to an understanding of interaction between
      the two extracts. The investigation was carried out using two different doses. A
      comparison was made with the response of individual plant extracts at the
      previously studied effective dose in adult Wistar rats rendered hyperthyroidic by
      daily injections of L-thyroxine (300 microg/kg body wt., s.c.). Propylthiouracil
      (PTU), an antithyroid drug, was used as a reference compound. Alterations in
      serum triiodothyronine (T3), thyroxine (T4), glucose, hepatic glucose-6
      phosphatase (G-6-Pase) and oxygen consumption were studied as end parameters.
      Superoxide dismutase (SOD), catalase (CAT) activities, lipid peroxidation (LPO)
      and reduced glutathione (GSH) were examined to reveal any toxic effects of the
      drugs. The combined effects of Trigonella and Allium at 200 and 500 mg/kg body
      wt. respectively, were equipotent as compared to the individual extracts in
      lowering the serum concentrations of T3 and T4 in hyperthyroidic rats. Our
      findings reveal that some plant extracts in combination may not always prove to
      be synergistic. It is therefore suggested that Trigonella foenum-graecum and
      Allium sativum extracts may be used individually and not together in the
      regulation of hyperthyroidism.

PMID- 14692728
TI  - Argentinian plant extracts with relaxant effect on the smooth muscle of the
      corpus cavernosum of guinea pig.
AB  - Extracts of different polarity from Baccharis trimera, Haplopappus rigidus
      Huperzia saururus, Maytenus ilicifolia, Satureja parvifolia and Senecio
      eriophyton were tested for their relaxant activity on smooth muscle using L
      phenylephrine precontracted strips of corpus cavernosum obtained from Guinea
      pigs. Highly significant and dose dependent results were obtained with the
      dichloromethane extracts of H. saururus (87% of relaxation at the dose of 10
      mg/ml), S. parvifolia (95% of relaxation at 2.5 mg/ml) and S. eriophyton (94% of
      relaxation at 5 mg/ml). Similar effects were observed with the methanol extracts
      of H. saururus (88% of relaxation at 10 mg/ml) and S. parvifolia (84% of
      relaxation at 10 mg/ml). These results were comparable to those obtained with the
      dichloromethane and methanol extracts of the well known Mexican species Turnera
      diffusa. Moreover, the aqueous extract of H. rigidus and the aqueous and methanol
      extracts of S. eriophyton were highly effective in a dose dependent manner (more
      than 90% of relaxation at the dose of 10 mg/ml). Significant results, but with a
      lower overall relaxant activity (about 70% of relaxation at 10 mg/ml), could also
      be obtained with the aqueous extract of S. parvifolia and with the dichlormethane
      and methanol extracts of B. trimera and M. ilicifolia. The positive controls with
      Sildenafil citrate at doses ranging from 0.35 to 35 microg/ml yielded moderate
      effects (up to 46% of relaxation at 35 microg/ml). The effects observed in the
      present study seem to validate the folk medicinal use of the tested plants and
      open new ways in the search for natural products with vasodilatory effects.

PMID- 14692729
TI  - Hypoglycemic effect of Sclerocarya birrea [(A. Rich.) Hochst.] [Anacardiaceae]
      stem-bark aqueous extract in rats.
AB  - This study was undertaken to evaluate the hypoglycemic effect of Sclerocarya
      birrea [(A. Rich.) Hochst.] subspecies caffra (Sond.) Kokwaro [family:
      Anacardiaceae] stem-bark aqueous extract in normal (normoglycemic) and in
      streptozotocin (STZ)-treated, diabetic Wistar rats. In one set of experiments,
      graded doses of S. birrea stem-bark aqueous extract (SB, 100-800 mg/kg p.o.) were
      separately administered to groups of fasted normal and fasted diabetic rats. In
      another set of experiments, a single dose of the plant aqueous extract (SB, 800
      mg/kg p.o.) was used. The hypoglycemic effect of this single dose (SB, 800 mg/kg
      p.o.) of S. birrea stem-bark aqueous extract was compared with that of
      chlorpropamide (250 mg/kg p.o.) in both fasted normal and fasted diabetic rats.
      Following acute treatment, relatively moderate to high doses of S. birrea stem
      bark extract (SB, 100-800 mg/kg p.o.) produced dose-dependent, significant
      reductions (P < 0.05-0.001) in the blood glucose concentrations of both fasted
      normal and fasted diabetic rats. Chlorpropamide (250 mg/kg p.o.) also produced
      significant reductions (P < 0.05-0.001) in the blood glucose concentrations of
      the fasted normal and fasted diabetic rats. Administrations of the single dose of
      S. birrea stem-bark aqueous extract (SB, 800 mg/kg p.o.) significantly reduced (P
      0.01 < 0.001) the blood glucose levels of both fasted normal (normoglycemic) and
      fasted STZ-treated, diabetic rats. The results of this experimental animal study
      indicate that aqueous extract of Sclerocarya birrea possesses hypoglycemic
      activity, and thus lend credence to the suggested folkloric use of the plant in
      the management and/or control of adult-onset, type-2 diabetes mellitus in some
      African communities.

PMID- 14692730
TI  - In vitro cytotoxicity of tanshinones isolated from Salvia miltiorrhiza Bunge
      against P388 lymphocytic leukemia cells.
AB  - The cytotoxic effect of four tanshinones isolated from the dried root of Salvia
      miltiorrhiza Bunge (Lamiaceae) were studied in vitro using P388 lymphocytic
      leukemia cells. Tanshinone I and tanshinone IIA were shown to be quite strongly
      cytotoxic against the cells (86.76% and 56.05% cell inhibition at 25 microg/ml).
      Dihydrotanshinone I and cryptotanshinone, which lack of saturation at C-15,
      showed little cytotoxicity (13.71% and 39.21% cell inhibition at 25 microg/ml).
      The results also revealed a structure activity relationship. We suggest that the
      unsaturation at C-15 and saturation on ring A may be critical structural
      components for cytotoxicity in these diterpenes.

PMID- 14692731
TI  - Ten years of complementary medicine at Exeter University.

PMID- 14692732
TI  - A review of clinical and experimental observations about antidepressant actions
      and side effects produced by Hypericum perforatum extracts.
AB  - Hypericum perforatum is an herbaceous perennial plant, also known as "St. John's
      wort", used popularly as a natural antidepressant. Although some clinical and
      experimental studies suggest it has some properties similar to conventional
      antidepressants, the proposed mechanism of action seems to be multiple: a non
      selective blockade of the reuptake of serotonin, noradrenaline and dopamine; an
      increase in density of serotonergic and dopaminergic receptors and an increased
      affinity for GABAergic receptors; moreover, the inhibition of monoaminoxidase
      enzyme activity has been involved. In any case, the increase of monoamine
      concentrations in the synaptic cleft resembles several actions exerted by
      clinically effective antidepressants. In the present article, we review some of
      the controversial evidence derived from clinical and experimental studies
      suggesting that H. perforatum exerts antidepressant-like actions, and we also
      review some of its side effects, such as nausea, rash, fatigue, restlessness,
      photosensitivity, acute neuropathy, and even episodes of mania and serotonergic
      syndrome when administered simultaneously with other antidepressant drugs. All of
      the foregoing suggests that H. perforatum extracts appear to exert potentially
      significant pharmacological activity involving several neurotransmission systems
      supposed to be involved in the pathophysiology of depression. However, little
      information regarding the safety of H. perforatum is available, including
      potential herb-drug interactions. There is a need for additional research on the
      pharmacological and biochemical activity of H. perforatum, as well as its side
      effects and its several bioactive constituents to further elucidate the
      mechanisms of antidepressant actions.

PMID- 14692733
TI  - Proposals to enhance the quality of observational cohort studies.
AB  - For herbal medicinal products the methodology of observational cohort studies
      (observational studies, drug monitoring studies, Anwendungsbeobachtung)
      represents a useful addition to clinical trials. The key objectives are the
      documentation of efficacy in particular under conditions of everyday medical
      practice in authentic patients and the documentation of the safety profile.
      Supplementary to earlier activities, members of the "Clinical Trials of Herbal
      Medicinal Products" Working Party of the German Society for Phytotherapy have
      therefore again addressed the issue of observational cohort studies for to
      enhance the informative value and importance of this clinical research
      methodology. Recommendations were developed on quality aspects, methodological
      approaches of observation parameters, and for the reporting of the study's
      results. Properly planned and conducted observational cohort studies may
      contribute to the documentation and proof of well-established medicinal use
      according the EU Directive 2001/83/EC.

PMID- 14692734
TI  - Jumping to conclusions.

PMID- 14692735
TI  - Biindanylidenes: role of central bond torsion in nonvertical triplet excitation
      transfer to the stilbenes.
AB  - The stilbenes were proposed to function as nonvertical triplet excitation (NVET)
      acceptors for energy-deficient donors because rotation about the central bond
      diminishes the energy gap between ground and triplet energy surfaces. Recently,
      the role of central bond torsion in facilitating NVET to cis-stilbene (c-St) was
      questioned because the behavior of 2,3-diphenylnorbornene as a triplet energy
      acceptor is similar to that of cis-stilbene. On the basis of the assumption that
      the rigidity of the norbornene skeleton precludes torsional displacement of the
      phenyl rings in the triplet state, an alternative mechanism was proposed
      involving phenyl-vinyl torsion as the key reaction coordinate for NVET to c-St.
      However, this proposal is inconsistent with theory, which predicts that the
      triplet state energy minimum corresponds to a geometry with significant
      displacement of the phenyl rings of 2,3-diphenylnorbornene from a common plane.
      We now provide experimental evidence demonstrating that central bond torsion is
      the key coordinate for NVET to stilbenes. Comparison of the activation parameters
      for the two rigid stilbene analogues, cis- and trans-1,1'-biindanylidene (c-Bi
      and t-Bi) to those for the stilbenes, shows that the excitation transfer
      processes remain nonvertical despite the strong structural inhibition of phenyl
      vinyl torsion; the relatively small preexponential factors of the respective
      isomers are almost identical. Their magnitude is a measure of the attenuation
      introduced by Franck-Condon overlap factors which decrease as the torsional state
      quantum number corresponding to the transition state increases. These results and
      results from theoretical calculations are consistent with central bond torsion as
      the key reaction coordinate in NVET to the biindanylidenes and the stilbenes. The
      crystal structure of t-Bi shows it to be strictly planar, eliminating phenyl
      vinyl torsion toward planarity as a crucial NVET reaction coordinate.

PMID- 14692736
TI  - An iron-peroxo porphyrin complex: new synthesis and reactivity toward a Cu(II)
      complex giving a heme-peroxo-copper adduct.
AB  - Side-on eta2-peroxo-iron porphyrins are strong nucleophiles. In cytochrome P450
      like aromatase and other enzymes, such species are postulated as the active
      oxidants. In cytochrome c oxidase, hemea3-peroxo, hemea3-hydroperoxo, or hemea3
      (mu-peroxo)-copper species are proposed as transient intermediates forming prior
      to O-O bond cleavage. In this report, we describe (1) a facile method for
      reduction of a heme-O2 species [(F8TPP)FeIII(O2-)(S)] (2), generating the ferric
      peroxo porphyrin complex [(F8TPP)FeIII(O22-)]- (3) (UV-vis, THF: lambdamax = 435
      (Soret), 540(sh), 561; EPR: g = 8.7, 4.2), and (2) that this can be subsequently
      reacted with a ligand-copper(II) complex, [CuII(TMPA)-(CH3CN)](ClO4)2 (4),
      affording a heme-peroxo-copper heterobinuclear compound, [(F8TPP)FeII(O22-)
      CuII(TMPA)](ClO4) (5). Generation of [(F8TPP)FeIII(O22-)]- (3) using cobaltocene
      as a one-electron reductant was monitored by UV-vis, EPR, and 1H NMR
      spectroscopies. Reaction between 3 and 4 was followed by UV-vis spectroscopy, and
      the product 5 could be precipitated and characterized. Coordination by copper(II)
      in 5 makes possible further reduction of the mu-peroxo complex by cobaltocene
      yielding the mu-oxo analogue, [(F8TPP)FeIII(O2-)-CuII(TMPA)](ClO4) (6).

PMID- 14692737
TI  - A chemoenzymatic approach toward the rapid and sensitive detection of O-GlcNAc
      posttranslational modifications.
AB  - We report a new chemoenzymatic strategy for the rapid and sensitive detection of
      O-GlcNAc posttranslational modifications. The approach exploits the ability of an
      engineered mutant of beta-1,4-galactosyltransferase to selectively transfer an
      unnatural ketone functionality onto O-GlcNAc glycosylated proteins. Once
      transferred, the ketone moiety serves as a versatile handle for the attachment of
      biotin, thereby enabling chemiluminescent detection of the modified protein.
      Importantly, this approach permits the rapid visualization of proteins that are
      at the limits of detection using traditional methods. Moreover, it bypasses the
      need for radioactive precursors and captures the glycosylated species without
      perturbing metabolic pathways. We anticipate that this general chemoenzymatic
      strategy will have broad application to the study of posttranslational
      modifications.

PMID- 14692738
TI  - Measurements of single-molecule electromechanical properties.
AB  - The electromechanical properties of a single molecule covalently attached to two
      gold electrodes are studied by simultaneously measuring the conductance and the
      force during the stretching of the molecule. The conductance, the spring constant
      of the molecular junction, and the dependence of the conductance on the
      stretching force are determined. Like the conductance, the spring constant of a
      molecule depends also on the molecule-electrode contacts. The forces required to
      break the molecule-gold contacts are 1.5 nN for alkanedithiols and 0.8 nN for
      4,4' bipyridine, indicating that the breakdowns take place at the Au-Au bond and
      at the N-Au bond, respectively.

PMID- 14692739
TI  - Synthesis of porous wires from directed assemblies of nanospheres.
AB  - A method is reported for the fabrication of wires with extended pore structures.
      Nanospheres are initially infiltrated into the one-dimensional channels of
      alumina or polymer porous membranes. Metal is then electrochemically deposited
      within the channels. Removal of the membrane and nanospheres results in porous
      wires. The production of 1-mum diameter wires with 300- or 500-nm diameter pores
      and 300-nm diameter wires with 140-nm pores illustrates the utility of this
      approach. Contacts between the spheres and the channel wall result in openings on
      the surface of the wires, and contacts between the spheres themselves produce
      openings between adjacent pores. Some short-range ordering of the spheres within
      the channels, as reflected in the wire pore structure, is evident.
      Characterization of the porous wires by electron microscopy is presented, and the
      potential applications of materials is discussed.

PMID- 14692740
TI  - Cadmium selenide quantum wires and the transition from 3D to 2D confinement.
AB  - Soluble CdSe quantum wires are prepared by the solution-liquid-solid mechanism,
      using monodisperse bismith nanoparticles to catalyze wire growth. The quantum
      wires have micrometer lengths, diameters in the range of 5-20 nm, and diameter
      distributions of +/-10-20%. Spectroscopically determined wire band gaps compare
      closely to those calculated by the semiemipirical pseudopotential method,
      confirming 2D quantum confinement. The diameter dependence of the quantum wire
      band gaps is compared to that of CdSe quantum dots and rods. Quantum rod band
      gaps are shown to be delimited by the band gaps of dots and wires of like
      diameter, for short and long rods, respectively. The experimental data suggest
      that a length of ca. 30 nm is required for the third dimension of quantum
      confinement to fully vanish in CdSe rods. That length is about six times the bulk
      CdSe exciton Bohr radius.

PMID- 14692741
TI  - A new self-penetrating uniform net, (8,4) (or 8(6)), containing planar four
      coordinate nodes.
AB  - Hydrothermal reaction of 3-(3-pyridyl)acrylic acid (pyaraH) with NiCl2 and NaOH
      results in formation of different polymorphs at different temperatures. alpha
      Ni(pyara)2(H2O)2 forms at 180 degrees C, and has a 3D polymeric structure. The
      topology of the network is that of a self-penetrating, four-coordinate (8,4)
      network (Schlafli symbol 86). This is the first uniform net to contain only
      planar four-coordinate nodes, and it is also the first four-coordinate uniform
      net not to have the Schlafli symbol 66. Tauhis fundamental network topology has
      been previously unrecognized. Tauhe second polymorph, the beta phase, forms from
      an analogous reaction at 150 degrees C, and contains 1D chains hydrogen bonded
      into a 3D network.

PMID- 14692742
TI  - Conversion of a tyrosine kinase protein substrate to a high affinity ligand by
      ATP linkage.
AB  - Protein kinases often show low affinity for their protein substrates, which makes
      it difficult to study kinase-substrate interactions. Here, we show using
      expressed protein ligation with the signaling protein Src that it is feasible to
      install a covalently linked ATP moiety into the tail of Src, generating a
      semisynthetic protein with a high affinity for its cognate tyrosine kinase, Csk.
      It is also established that this Src-ATP conjugate can be used to selectively
      pull down Csk from a complex protein mixture. This work outlines a general
      strategy for identifying an unknown kinase that is responsible for the
      phosphorylation of a protein substrate on a site of interest.

PMID- 14692743
TI  - Detection of amines and unprotected amino acids in aqueous conditions by
      formation of highly fluorescent iminium ions.
AB  - Properly substituted coumarin aldehydes can be used to detect amines and amino
      acids under neutral, high ionic strength conditions by the formation of highly
      fluorescent iminium ions. The fluorescence of one sensor increases by 26-fold
      upon the addition of glycine. This strong florescent response is attributed to
      hydrogen bonding of the chromophore carbonyl by the acidic iminium proton.

PMID- 14692744
TI  - A solution-phase, precursor route to polycrystalline SnO2 nanowires that can be
      used for gas sensing under ambient conditions.
AB  - This paper describes a solution-based, precursor method for the facile synthesis
      of uniform nanowires containing rutile SnO2 nanocrystallites. In a typical
      procedure, nanowires of approximately 50 nm in diameters and up to 30 mum in
      length were obtained as a white precipitate by refluxing SnC2O4.2H2O and
      poly(vinylpyrrolidone) in ethylene glycol. Structural analyses by XRD, FT-IR, and
      TGA indicate that these highly anisotropic nanostructures were formed in an
      isotropic medium through the aggregation of chainlike precursors that were, in
      turn, formed via polyol-mediated oligomerization. These nanowires could be
      further converted to polycrystalline SnO2 by calcination in air at 500 degrees C.
      The resultant nanowires of SnO2 were highly porous and could be used for gas
      sensing with improved sensitivity and reversibility under ambient conditions. We
      have also demonstrated that this new approach could be extended to generate
      polycrystalline nanowires of other metal oxides such as In2O3 and anatase TiO2.

PMID- 14692745
TI  - Heterobimetallic catalysis in asymmetric 1,4-addition of O-alkylhydroxylamine to
      enones.
AB  - A heterobimetallic YLi3tris(binaphthoxide) catalyst (YLB) promoted a 1,4-addition
      of O-methylhydroxylamine in high enantiomeric excess (up to 97% ee). Catalyst
      loading was reduced to as little as 0.5 mol %, still affording the 1,4-adduct in
      96% yield and 96% ee. A high concentration of substrates and the scalability of
      the present system is also practically useful. The results suggested that the
      heterobimetallic catalysis was not deactivated even in the presence of excess
      amine under highly concentrated conditions. A Y and Li bimetallic cooperative
      function was essential for a high catalyst turnover number.

PMID- 14692746
TI  - Discrimination of guests encapsulation in large hexameric molecular capsules in
      solution: pyrogallol[4]arene versus resorcin[4]arene capsules.
AB  - NMR experiments demonstrate that, although 2b and 3b form hexameric capsules in
      chloroform solutions and despite the very similar building units of these
      hexamers, 3b encapsulates only the noncharged trialkylamines while 2b can
      encapsulate both the noncharged trialkylamines and the respective ammonium salts
      obtained by the addition of DCl. In fact, it was found that protonation that
      forms in situ the ammonium salt ejects the guest from the hexameric capsule of
      3b. This is a general observation as it was found for guests containing alkyl
      chains of four, five, six, and eight carbons.

PMID- 14692747
TI  - Unraveling the mystery surrounding cholesterol's condensing effect.
AB  - The results of nearest-neighbor recognition experiments that have been carried
      out with exchangeable dimers derived from 1,2-dimyristoyl-sn-glycero-3
      phosphoethanolamine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, in the
      presence of cholesterol, dihydrocholesterol, coprostanol, cholestane, cholesteryl
      methy ether, and sitosterol, provide strong support for a condensing mechanism in
      which the flexible acyl chains of the phospholipids complement, perfectly, the
      shape of neighboring sterols, thereby leading to a high number of hydrophobic
      contacts and tight packing.

PMID- 14692748
TI  - Assessing the magnitude of folding forces along the oxidative folding pathway of
      multi-disulfide-containing proteins.
AB  - Oxidative folding involves the acquisition of the native set of disulfide bonds
      and native structure of a protein from its reduced, unfolded form. Two major
      factors that influence the distribution of disulfide bonds (over their
      entropically favored probability of formation) during the regeneration,
      eventually favoring and sustaining the native set of disulfide bonds, are
      enthalpic interactions that lead to conformational ordering among intermediates
      and conformational folding, resulting in native (or nativelike) structure which
      protects the native disulfide bonds from reduction and intramolecular thiol
      disulfide exchange reactions. Here, we report a novel technique to provide a
      quantitative description of the enthalpic and conformational folding forces
      present at any stage of the oxidative folding process of multi-disulfide
      containing proteins which is made feasible by assessing their ability to form
      "structures" that are able to protect disulfide bonds from reduction.

PMID- 14692749
TI  - Monopod, bipod, tripod, and tetrapod gold nanocrystals.
AB  - Multipod gold nanocrystals have been synthesized via a simple solution-phase
      chemical reduction method at room temperature. Two types of structurally
      different particles are observed, including the regular tripod, which lies on the
      substrate with its {111} plane, and the cross-like tetrapod that sits on its
      {100} plane. Both structures have pods of 10 nm sizes and grow along 110
      directions. Variously shaped particles, including tadpole-like or teardrop-like
      monopods, 90 degrees L-shaped, 180 degrees I-shaped, and 120 degrees V-shaped
      bipods, T-shaped, Y-shaped, and regular triangular tripods, and cross-like
      tetrapods, have been produced. Due to the high conductivity of metal, these
      branched structures are quite promising considering their applications as
      interconnections in the "bottom-up" self-assembly approach toward future
      nanocircuits and nanodevices, as well as in other related fields.

PMID- 14692750
TI  - Rotational isomerism in acetic acid: the first experimental observation of the
      high-energy conformer.
AB  - The high-energy conformer of acetic acid (cis-AA) is produced in an Ar matrix by
      vibrational excitation of the OH stretching overtone of the ground conformational
      state (trans-AA). IR-absorption spectroscopy provides a clear identification of
      the reaction product. cis-AA converts back to trans-AA in a time scale of minutes
      at 8 K by tunneling.

PMID- 14692751
TI  - Uncoupled forms of tyrosine hydroxylase unmask kinetic isotope effects on
      chemical steps.
AB  - Tyrosine hydroxylase (TyrH) catalyzes the hydroxylation of tyrosine to
      dihydroxyphenylalanine. In the proposed mechanism, a ferryl-oxo species attacks
      the aromatic ring of tyrosine, forming a cationic intermediate. However, no
      significant isotope effect is found for wild-type TyrH when 3,5-2H2-tyrosine is
      used as a substrate. The isotope effect has now been determined with 3,5-2H2
      tyrosine using mutant forms of TyrH in which the oxidation of the pterin is
      uncoupled from hydroxylation of the amino acid. Three mutant enzymes exhibit
      significant inverse deuterium isotope effects and inverse solvent isotope
      effects. A proton inventory for the E326A enzyme is consistent with a normal
      solvent isotope effect of 2.4 on an unproductive step. The results support the
      proposed mechanism and demonstrate the utility of using mutant proteins with
      branched pathways to reveal isotope effects which are masked in the wild-type
      enzyme.

PMID- 14692752
TI  - Adsorption isotherm and other properties of methane in zeolite A from an
      intermolecular potential derived from ab initio calculations.
AB  - A classical Lennard-Jones potential is derived from a fit to the ab initio
      energies obtained from an all-electron mixed-basis calculation for methane in
      zeolite LTA. The potential predicts the heat of adsorption, adsorption isotherm,
      and self-diffusivity of methane in excellent agreement with experiment. This
      study suggests, for the first time, that ab initio energies-in addition to
      experimental data-can form a good basis for derivation of accurate classical
      potentials between organic and inorganic elements.

PMID- 14692753
TI  - A general method for the Suzuki-Miyaura cross-coupling of sterically hindered
      aryl chlorides: synthesis of di- and tri-ortho-substituted biaryls in 2-propanol
      at room temperature.
AB  - The catalytic formation of di- and trisubstituted ortho biaryl junctions has been
      achieved using a palladacylce pre-catalyst bearing a N-heterocyclic carbene
      ligand. This transformation is performed at room temperature in technical grade 2
      propanol.

PMID- 14692754
TI  - Nanocable-aligned ZnS tetrapod nanocrystals.
AB  - An effective method for synthesizing ZnS-core/carbon-sheath nanocables and
      nanocable-aligned ZnS tetrapod nanocrystals has been developed. Nanocable
      heterostructures and nanocable-linked ZnS tetrapods were synthesized in a
      controllable way. The tetrapods are single crystalline cubic ZnS with triangular
      prism branches stretching out in four {111} directions. The tetrapods were
      aligned together with ZnS-C nanocables along the [100] direction.

PMID- 14692755
TI  - Long-lived charge-separated state leading to DNA damage through hole transfer.
AB  - The hole transfer causes the long-lived charge-separated state in DNA during the
      photosensitized one-electron oxidation of DNA. The combination of the transient
      absorption measurement and DNA damage quantification by HPLC clearly demonstrated
      that the yield of the DNA damage correlates well with the lifetime of the charge
      separated state.

PMID- 14692756
TI  - Synthesis of optically active oligonaphthalenes via second-order asymmetric
      transformation.
AB  - Synthesis of numerous optically active rod-shaped oligo(2,3
      dioxyfunctionalized)naphthalenes connected at their 1,4-positions was achieved
      using oxidative coupling under CuCl2/alpha-methylbenzylamine conditions by second
      order asymmetric transformation. We believe this method is practical and should
      contribute to the field of material science.

PMID- 14692757
TI  - Efficient aziridination of olefins catalyzed by a unique disilver(I) compound.
AB  - A unique disilver(I) compound is an efficient catalyst for aziridination of
      olefins.

PMID- 14692758
TI  - Theoretical analysis of peroxynitrous acid: characterization of its elusive
      biradicaloid (HO...ONO) singlet states.
AB  - Various high levels of theory (DFT, QCISD, BD(TQ), and CASSCF) have been applied
      to the characterization of two higher-lying biradicaloid singlet states of
      peroxynitrous acid. A singlet minimum (cis-2) was located that had an elongated O
      O distance of 2.17 A and was only 14.4 kcal/mol [UB3LYP/6-311+G(3df,2p)] higher
      in energy than its cis-peroxynitrous acid ground-state precursor. A trans
      metastable higher-lying singlet (trans-2) was 12.8 kcal/mol higher in energy than
      ground-state HO-ONO. Complete active space calculations [CAS(12,10)/6-311+G(d,p)]
      predicted the optimized geometries of these cis and trans metastable singlets to
      be quite close to those obtained with the DFT method. Geometry optimization of
      both cis- and trans-2 within the COSMO solvent model suggest that both exist as
      energy minima in polar media with elongated O-O distances of 2.14 and 2.09 A.
      Both cis- and trans-2 exist as hydrogen-bonded complexes with several water
      molecules. These collective data suggest that solvated forms of cis-2.3H2O and
      trans-2.3H2O represent the elusive higher-lying biradicaloid minima that have
      been previously advocated (J. Am. Chem. Soc. 1996, 118, 3125) as the metastable
      forms of peroxynitrous acid (HOONO*).

PMID- 14692759
TI  - Novel reversible ionic-to-covalent transition in a highly conducting TTF
      derivative.
AB  - TTF produces two completely different phenomena with the different isomers of
      chloranil; with the para isomer it produces an insulating, alternating stack,
      ambient temperature neutral solid. While with the ortho isomer, it produces a
      more interesting system consisting of interconvertible conducting ionic and
      covalent components.

PMID- 14692760
TI  - Kinetic isotope effects on the rate-limiting step of heme oxygenase catalysis
      indicate concerted proton transfer/heme hydroxylation.
AB  - Heme oxygenase (HO) catalyzes the O2 and NADPH/cytochrome P450 reductase
      dependent conversion of heme to biliverdin, free iron ion, and CO through a
      process in which the heme participates as both dioxygen-activating prosthetic
      group and substrate. We earlier confirmed that the first step of HO catalysis is
      a monooxygenation in which the addition of one electron and two protons to the HO
      oxy-ferroheme produces ferric-alpha-meso-hydroxyheme (h). Cryoreduction/EPR and
      ENDOR measurements further showed that hydroperoxo-ferri-HO converts directly to
      h in a single kinetic step without formation of a Compound I. We here report
      details of that rate-limiting step. One-electron 77 K cryoreduction of human oxy
      HO and annealing at 200 K generates a structurally relaxed hydroperoxo-ferri-HO
      species, denoted R. We here report the cryoreduction/annealing experiments that
      directly measure solvent and secondary kinetic isotope effects (KIEs) of the rate
      limiting R --> h conversion, using enzyme prepared with meso-deuterated heme and
      in H2O/D2O buffers to measure the solvent KIE (solv-KIE), and the secondary KIE
      (sec-KIE) associated with the conversion. This approach is unique in that KIEs
      measured by monitoring the rate-limiting step are not susceptible to masking by
      KIEs of other processes, and these results represent the first direct measurement
      of the KIEs of product formation by a kinetically competent reaction intermediate
      in any dioxygen-activating heme enzyme.The observation of both solv-KIE(298) =
      1.8 and sec-KIE(298) = 0.8 (inverse) indicates that the rate-limiting step for
      formation of h by HO is a concerted process: proton transfer to the hydroperoxo
      ferri-heme through the distal-pocket H-bond network, likely from a carboxyl group
      acting as a general acid catalyst, occurring in synchrony with bond formation
      between the terminal hydroperoxo-oxygen atom and the alpha-meso carbon to form a
      tetrahedral hydroxylated-heme intermediate. Subsequent rearrangement and loss of
      H2O then generates h.

PMID- 14692761
TI  - Density functional study of the insertion and ring-opening mechanism of MCP over
      Cp2LaH and Cp2LuH catalysts.
AB  - The insertion and ring opening of methylenecyclopropane (MCP) catalyzed by Cp2LnH
      (Ln = La and Lu) was investigated using DFT method. Geometries and energies of
      the reactants, minima, and transition states for this reaction were obtained. The
      present study indicates the formation of Cp2LaH-MCP complex followed by 1,2
      insertion through a tetrahedral transition state with subsequent ring opening at
      the proximal bond via hydrogen transfer transition state resulting in the
      formation of the final product.

PMID- 14692762
TI  - Elimination of oxidative degradation during the per-O-methylation of
      carbohydrates.
AB  - The possible oxidative degradation mechanism occurring during the per-O
      methylation of carbohydrates in dimethyl sulfoxide with methyl iodide in the
      presence of base is described. Evidence is presented that this process occurs
      only under anhydrous conditions when there is a long reaction time between the
      carbohydrate dissolved in dimethyl sulfoxide and methyl iodide, followed by
      reaction with the base. Under these specific conditions, the oxidative
      degradation of alditols, and cyclic carbohydrates, with and without a free
      hemiacetal group, is observed. The reaction between carbohydrate and methyl
      iodide in dimethyl sulfoxide can result in a complete oxidative degradation
      depending on the type of carbohydrate and the time of reaction. The oxidative
      degradation can be accelerated by replacing methyl iodide with dimethyl sulfate.
      Mass spectrometric identification of the degradation products of d-glucitol
      indicates simultaneous oxidation processes at all the hydroxyl groups, with site
      dependent rates of their reactivity. This oxidative process is not a
      characteristic of the methylation of carbohydrates in dimethyl sulfoxide with
      methyl iodide in the presence of solid sodium hydroxide and can be totally
      avoided by treating the carbohydrate with powdered sodium hydroxide before
      introduction of methyl iodide under nonanhydrous conditions, or by adding a trace
      of water in dimethyl sulfoxide before methyl iodide, or by using N,N
      dimethylacetamide as the solvent. The degradation of the per-O-methylated
      carbohydrates in the liquid-liquid extraction process is also taken into account,
      and it is found that the degradation process can be avoid by neutralization of
      the base before extraction, by using benzene or tetrachloromethane as extraction
      solvent, and by drying the final organic extract.

PMID- 14692763
TI  - On the extended beta-conformation propensity of polypeptides at high temperature.
AB  - At room temperature, natural polypeptides exposed to high concentrations of a
      strong denaturant nearly attain the circular dichroism spectra characteristic of
      random coils. As temperature is increased, the spectra begin to show the
      signature of a substantial fraction of extended chain, the structure common in
      beta-sheets. This structural propensity at high temperature is not altered by
      concentration changes over a greater than 1000-fold range, so it is not caused by
      aggregation. Four proteins with different folds and varying amounts of alpha
      helical and beta-sheet secondary structure, in the presence or absence of
      denaturant, all were subject to extended chain formation upon heating. This
      effect arises naturally from the steric constraints associated with polypeptides
      and is probably counteracted, not enhanced, by hydrophobic interactions.
      Molecular dynamics simulations in the 298-1000 K range reveal an attractive
      potential of mean force in the extended chain region of the Ramachandran diagram,
      which broadens as the temperature is raised. We also demonstrate a direct
      correlation between extended structure content and the rate of aggregation
      kinetics. Thus pre-existing extended structure could funnel proteins into
      aggregates.

PMID- 14692764
TI  - Design and construction of glutamine binding proteins with a self-adhering
      capability to unmodified hydrophobic surfaces as reagentless fluorescence sensing
      devices.
AB  - The chemically and genetically remodeling of proteins with ligand binding
      specificities can be utilized to synthesize various protein-based microsensors
      for detecting single biomolecules. Here, we describe the construction and
      characterization of fluorophore-labeled glutamine binding proteins (QBP) and
      derivatives coupled to the independently designed hydrophobic polypeptide (E12)
      that can adhere onto solid surfaces via hydrophobic interactions. The single
      cysteine mutant (N160C QBP) modified with the three environmentally sensitive
      fluorescent dyes (IAANS, acrylodan, and IANBD ester) showed increased changes in
      fluorescence intensity induced by glutamine binding. The use of these conjugates
      as reagentless fluorescence sensors enables us to determine the glutamine
      concentrations (0.1-50 microM) in homogeneous solution. The fusion of N160C QBP
      with E12, (Gly4-Ser)n spacers (GSn), and IANBD resulted in the novel fluorescence
      sensing elements having an adhering capability to hydrophobic surfaces of
      unmodified microplates. In ELISA and fluorescence experiments for the microplates
      treated with a series of the conjugates, IANBD-labeled N160C QBP-GS1-E12
      displayed the best reproducibility in adhesion onto the hydrophobic surfaces and
      the precise correlation between fluorescence changes and glutamine
      concentrations. The performance of the biosensor-attached microplate for
      glutamine titrations demonstrated that the hydrophobic interaction of E12 with
      solid surfaces is useful for effective immobilization of proteins that need
      specific conformational movements in recognizing particular biomolecules.
      Therefore, the technique using E12 as a surface-linking domain for protein
      adhesion onto unmodified substrates could be applied effectively to prepare
      microplates/arrays for a wide variety of high-throughput assays on chemical and
      biological samples.

PMID- 14692765
TI  - Probing the requirements for recognition and catalysis in Fpg and MutY with
      nonpolar adenine isosteres.
AB  - The Escherichia coli DNA repair enzymes Fpg and MutY are involved in the
      prevention of mutations resulting from 7,8-dihydro-8-oxo-2'-deoxyguanosine (OG)
      in DNA. The nonpolar isosteres of 2'-deoxyadenosine, 4-methylbenzimidazole beta
      deoxynucleoside (B), and 9-methyl-1H-imidazo[4,5-b]pyridine beta-deoxynucleoside
      (Q), were used to examine the importance of hydrogen bonding within the context
      of DNA repair. Specifically, the rate of base removal under single-turnover
      conditions by the MutY and Fpg glycosylases from duplexes containing OG:B and
      OG:Q mismatches, relative to OG:A mismatches, was evalulated. The reaction of Fpg
      revealed a 5- and 10-fold increase in rate of removal of OG from duplexes
      containing OG:B and OG:Q base pairs, respectively, relative to an OG:A mispair.
      These results suggest that the lack of the ability to hydrogen bond to the
      opposite base facilitates removal of OG. In contrast, adenine removal catalyzed
      by MutY was much more efficient from an OG:A mispair-containing duplex (k2 = 12
      +/- 2 min(-1)) compared to the removal of B from an OG:B duplex (k(obs) < 0.002
      min(-1)). Surprisingly, MutY was able to catalyze base removal from the OG:Q
      containing substrate (k2 = 1.2 +/- 0.2 min(-1)). Importantly, the B and Q
      analogues are not deleterious to high-affinity DNA binding by MutY. In addition,
      the B and Q analogues are more susceptible to acid-catalyzed depurination
      illustrating that the enzyme-catalyzed mechanism is distinct from the
      nonenzymatic mechanism. Taken together, these results point to the importance of
      both N7 and N3 in the mechanism of adenine excision catalyzed by MutY.

PMID- 14692766
TI  - Development of a new family of conformationally restricted peptides as potent
      nucleators of beta-turns. Design, synthesis, structure, and biological evaluation
      of a beta-lactam peptide analogue of melanostatin.
AB  - Novel enantiopure (i)-(beta-lactam)-(Gly)-(i+3) peptide models, defined by the
      presence of a central alpha-alkyl-alpha-amino-beta-lactam ring placed as the
      (i+1) residue, have been synthesized in a totally stereocontrolled way by alpha
      alkylation of suitable N-[bis(trimethylsilyl)methyl]-beta-lactams. The structural
      properties of these beta-lactam pseudopeptides have been studied by X-ray
      crystallography, Molecular Dynamics simulation, and NOESY-restrained NMR
      simulated annealing techniques, showing a strong tendency to form stable type II
      or type II' beta-turns either in the solid state or in highly coordinating DMSO
      solutions. Tetrapeptide models containing syn- or anti-alpha,beta-dialkyl-alpha
      amino-beta-lactam rings have also been synthesized and their conformations
      analyzed, revealing that alpha-alkyl substitution is essential for beta-turn
      stabilization. A beta-lactam analogue of melanostatin (PLG amide) has also been
      prepared, characterized as a type-II beta-turn in DMSO-d6 solution, and tested by
      competitive binding assay as a dopaminergic D2 modulator in rat neuron cultured
      cells, displaying moderate agonist activity in the micromolar concentration
      range. On the basis of these results, a novel peptidomimetic design concept,
      based on the separation of constraint and recognition elements, is proposed.

PMID- 14692767
TI  - Chemical characterization of alpha-oxohydrazone ligation on colloids: toward
      grafting molecular addresses onto biological vectors.
AB  - New mild and specific chemical strategies have been developed recently for the
      selective coupling of biological macromolecules. Among them, the hydrazone
      ligation strategy offers high chemoselectivity and versatility. We intended to
      use hydrazone ligation to target the controlled release of therapeutic agents by
      biological vectors (multilamellar vesicles called onion vectors). An accurate
      measure of ligation bond stability was needed to ensure that the ligation bond
      would stand long exposures to physiological conditions. In this study, we have
      completed a kinetic and thermodynamic characterization of hydrazone formation on
      a model reaction. The mechanism of the reaction in solution as well as in
      different self-organized systems (micelles, liposomes and multilamellar vesicles)
      was investigated. In solution, submicromolar stability was achieved as well as
      half-lives of several weeks. The kinetics and stability were both enhanced in
      colloidal media thanks to autoassociation effects. The results were expanded to
      the realistic case of RGD-peptide coupling to onion vectors. The RGD grafted
      onion vectors were then tested for their ability to bind endothelial cells in
      vitro.

PMID- 14692768
TI  - On the nature of the multivalency effect: a thermodynamic model.
AB  - A quantitative model is proposed for the analysis of the thermodynamic parameters
      of multivalent interactions in dilute solutions or with immobilized multimeric
      receptor. The model takes into account all bound species and describes
      multivalent binding via two microscopic binding energies corresponding to inter-
      and intramolecular interactions (Delta G(o)inter and Delta G(o)intra), the
      relative contributions of which depend on the distribution of complexes with
      different numbers of occupied binding sites. The third component of the overall
      free energy, which we call the "avidity entropy" term, is a function of the
      degeneracy of bound states, Omega(i), which is calculated on the basis of the
      topology of interaction and the distribution of all bound species. This term
      grows rapidly with the number of receptor sites and ligand multivalency, it
      always favors binding, and explains why multivalency can overcome the loss of
      conformational entropy when ligands displayed at the ends of long tethers are
      bound. The microscopic parameters and may be determined from the observed binding
      energies for a set of oligovalent ligands by nonlinear fitting with the
      theoretical model. Here binding data obtained from two series of oligovalent
      carbohydrate inhibitors for Shiga-like toxins were used to verify the theory. The
      decavalent and octavalent inhibitors exhibit subnanomolar activity and are the
      most active soluble inhibitors yet seen that block Shiga-like toxin binding to
      its native receptor. The theory developed here in conjunction with our protocol
      for the optimization of tether length provides a predictive approach to design
      and maximize the avidity of multivalent ligands.

PMID- 14692769
TI  - Folding of a stable DNA motif involves a highly cooperative network of
      interactions.
AB  - Hairpins are structural elements that play important roles in the folding and
      function of RNA and DNA. The extent of cooperativity in folding is an important
      aspect of the RNA folding problem. We reasoned that an investigation into the
      origin of cooperativity might be best carried out on a stable nucleic acid system
      with a limited number of interactions, such as a stable DNA hairpin loop. The
      stable d(cGNAg) hairpin loop motif (closing base pair in lower case; loop in
      upper case; N = A, C, G, or T) is stabilized through only three interactions: two
      loop-loop hydrogen bonds in a sheared GA base pair and a loop-closing base pair
      interaction. Herein, we investigate this network of interactions and test whether
      the loop-loop and loop-closing base pair interactions communicate. Thermodynamic
      measurements of nucleotide analogue substituted oligonucleotides were used to
      probe the additivity of the interactions. On the basis of double mutant cycles,
      all interactions were found to be nonadditive and interdependent, suggesting that
      loop-loop and loop-closing base pair interactions form in a highly cooperative
      manner. When double mutant cycles were repeated in the absence of the other
      interaction, nonadditivity was significantly reduced suggesting that coupling is
      indirect and requires all three interactions in order to be optimal. A
      cooperative network of interactions helps explain the structural and energetic
      bases of stability in certain DNA hairpins and paves the way for similar studies
      in more complex nucleic acid systems.

PMID- 14692770
TI  - Nucleation-elongation polymerization under imbalanced stoichiometry.
AB  - As a result of the helical structure of the polymeric product, the folding-driven
      polymerization of oligo(m-phenyleneethynylene) imines in solution should
      inherently show nucleation-elongation in chain growth. Here, we present evidence
      for this behavior based on results of polymerizations conducted under conditions
      of imbalanced stoichiometry. Because the polymerization proceeds via imine
      metathesis between a pair of bifunctional monomers of types A-A and B-B, the
      molar ratio of the polymerizing functional groups can be arbitrarily varied.
      Alternatively, stoichiometry can be controlled by the addition of a
      monofunctional oligomer. Similar results were obtained in both cases whereby the
      molecular weight distribution was significantly different from that expected for
      classical step-growth polymerizations. At equilibrium, high molecular weight
      polymers were observed to coexist with the monomer in excess. Thermodynamic
      equilibrium was established by showing that the same distribution was reached
      starting either from a monomer mixture or from high polymers to which one monomer
      was added. These results are in great contrast to the low molecular weight
      oligomers that were produced when the reaction was conducted by melt condensation
      of bifunctional aldehyde and amine monomers, a polymerization that apparently
      proceeds without the nucleation event. An equilibrium model that captures the
      features of nucleation-elongation under conditions of imbalanced stoichiometry
      qualitatively supports the monomer-polymer distribution observed experimentally.

PMID- 14692771
TI  - Beta-octafluorocorroles.
AB  - The one-pot corrole synthesis first reported by the Gross and Paolesse groups
      appears to have evolved into a remarkably general and predictable self-assembly
      based synthetic reaction. Gross's solvent-free procedure (refs 8 and 9) has
      proven particularly effective in our hands and, in fact, more general than
      originally claimed. In earlier work (ref 17), we showed that the reaction works
      for a variety of aromatic aldehyde starting materials and was not limited to
      relatively electron-deficient aldehydes, as reported by Gross and co-workers.
      Here, we show that the pyrrole component is also variable in that 3,4
      difluoropyrrole undergoes oxidative condensation with four different p-X
      substituted benzaldehydes to yield the corresponding beta-octafluoro-meso
      tris(para-X-phenyl)corroles (X = CF3, H, CH3, and OCH3). Further, we have
      prepared the Cu and FeCl derivatives of the beta-octafluorocorrole ligands. The
      XPS nitrogen 1s ionization potentials of these fluorinated ligands are some 0.7
      eV higher than those of the corresponding beta-unfluorinated ligands. The
      oxidation half-wave potentials of the Cu and FeCl complexes of the fluorinated
      corroles are also positively shifted by 300-400 mV relative to their beta
      unsubstituted analogues, demonstrating the strongly electron-deficient character
      of the fluorinated ligands. 1H NMR spectroscopy suggests that like their beta
      unfluorinated counterparts, the new beta-octafluorinated triarylcorroles act as
      substantially noninnocent ligands, i.e., exhibit corrole pi-cation radical
      character, in the FeCl complexes. Quantitatively, however, NMR spectroscopy and
      DFT calculations indicate that the beta-octafluorinated corroles are somewhat
      less noninnocent (i.e., carry less radical character) than their beta
      unfluorinated counterparts in the FeCl complexes. Temperature-dependent 19F NMR
      spectroscopy suggests that the Cu octafluorocorroles have a thermally accessible
      paramagnetic excited state, which we assign as a Cu(II) corrole pi-cation
      radical. We have previously reported that the electronic absorption spectra,
      particularly the Soret absorption maxima, of high-valent transition metal
      triarylcorroles are very sensitive to the nature of the substituents in the meso
      positions. In contrast, the Soret absorption maxima of free-base triarylcorroles
      are not particularly sensitive to the nature of the meso substituents. This
      scenario also holds for the fluorinated corroles described here. Thus, although
      the four free-base fluorinated triarylcorroles exhibit practically identical
      Soret absorption maxima, the Soret bands of the Cu derivatives of the same
      corroles red-shift by approximately 35 nm on going from the p-CF3 to the p-OCH3
      derivative.

PMID- 14692772
TI  - Intramolecular cycloadditions of cyclobutadiene with dienes: experimental and
      computational studies of the competing (2 + 2) and (4 + 2) modes of reaction.
AB  - Highly functionalized, cyclobutene-containing adducts are afforded through
      intramolecular cycloadditions between cyclobutadiene and tethered dienes. The
      cycloaddition displays the following reactivity trend: cyclobutadiene serves as a
      dienophile in intramolecular reactions when it is connected to the diene through
      a four-atom tether. In cases where a three-atom linker separates the two reaction
      partners, the cyclobutadiene can function as both a diene and dienophile,
      affording a mixture of vinylcyclobutane (2 + 2) and cyclohexene-containing
      cycloadducts (4 + 2). Theoretical studies provide insight into the factors
      influencing the various pericyclic pathways operative in this system. In cases
      where cyclobutadiene functions as a diene to generate vinylcyclobutanes, these (2
      + 2) adducts can be converted into the corresponding (4 + 2) cyclohexenyl
      products through a [3,3]-sigmatropic rearrangement.

PMID- 14692773
TI  - A mechanism-based inhibitor targeting the DD-transpeptidase activity of bacterial
      penicillin-binding proteins.
AB  - Penicillin-binding proteins (PBPs) are responsible for the final stages of
      bacterial cell wall assembly. These enzymes are targets of beta-lactam
      antibiotics. Two of the PBP activities include dd-transpeptidase and DD
      carboxypeptidase activities, which carry out the cross-linking of the cell wall
      and trimming of the peptidoglycan, the major constituent of the cell wall, by an
      amino acid, respectively. The activity of the latter enzyme moderates the degree
      of cross-linking of the cell wall, which is carried out by the former. Both these
      enzymes go through an acyl-enzyme species in the course of their catalytic
      events. Compound 6, a cephalosporin derivative incorporated with structural
      features of the peptidoglycan was conceived as an inhibitor specific for DD
      transpeptidases. On acylation of the active sites of dd-transpeptidases, the
      molecule would organize itself in the two active site subsites such that it
      mimics the two sequestered strands of the bacterial peptidoglycan en route to
      their cross-linking. Hence, compound 6 is the first inhibitor conceived and
      designed specifically for inhibition of DD-transpeptidases. The compound was
      synthesized in 13 steps and was tested with recombinant PBP1b and PBP5 of
      Escherichia coli, a dd-transpeptidase and a dd-carboxypeptidase, respectively.
      Compound 6 was a time-dependent and irreversible inhibitor of PBP1b. On the other
      hand, compound 6 did not interact with PBP5, neither as an inhibitor (reversible
      or irreversible) nor as a substrate.

PMID- 14692774
TI  - Hydroxy- and silyloxy-substituted TEMPO derivatives for the living free-radical
      polymerization of styrene and n-butyl acrylate: synthesis, kinetics, and
      mechanistic studies.
AB  - The synthesis of new 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) styryl
      derivatives as mediators for the living free-radical polymerization is described.
      Two of the alpha-methyl groups at the 2- and 6-position of the parent TEMPO
      styryl alkoxyamine have been replaced by hydroxymethyl and silyloxymethyl groups.
      To further increase the steric hindrance around the alkoxyamine oxygen atom, the
      remaining two methyl groups have been substituted with larger ethyl groups.
      Styrene polymerizations using hydroxy-substituted TEMPO derivatives are fast, but
      are not well-controlled. As previously shown for other OH-substituted
      alkoxyamines, intramolecular H-bonding leads to an acceleration of the C-O bond
      homolysis and, hence, to an acceleration of the polymerization process. However,
      the OH groups also increase the alkoxyamine decomposition rate constant. The
      kinetics of the C-O bond homolysis have been determined using EPR spectroscopy.
      Decomposition studies have been conducted with the aid of 1H NMR spectroscopy. In
      contrast to the OH-substituted alkoxyamines, highly hindered silyloxy-substituted
      TEMPO alkoxyamines turned out to be excellent mediator/initiators for the
      controlled styrene polymerization. Polystyrene with M(n) of up to 80 000 g/mol
      and narrow polydispersities (PDI) has been prepared using the new alkoxyamines.
      Reactions have been conducted at 105 degrees C; however, even at 90 degrees C
      controlled but slow polymerizations can be achieved. Furthermore, and more
      importantly, poly(n-butyl acrylates) with narrow PDIs (<1.15) have been prepared
      at 105 degrees C with the new alkoxyamines. Controlled acrylate polymerization
      can be conducted at temperatures as low as 90 degrees C. The silylated
      alkoxyamines presented belong to the most efficient initiator/mediators for the
      controlled acrylate polymerization known to date. The effect of the addition of
      free nitroxide on the acrylate polymerization is discussed. Moreover, the
      synthesis of diblock copolymers with narrow PDIs is described.

PMID- 14692775
TI  - Convergent synthesis of a GPI containing an acylated inositol.
AB  - A GPI of sperm CD52 was synthesized by a highly convergent procedure,
      representing the first chemical synthesis of a complex GPI having an acylated
      inositol. The presence of a large acyl group resulted in unusual properties and
      reactions of the relevant intermediates, which gave rise to a number of problems.
      To overcome the problems and achieve the target molecule, a new synthetic
      strategy was developed. First, the pseudodisaccharide of 2-O-palmitoylinositol
      was phospholipidated, and then the trimannose segment and the phosphoethanolamine
      group were sequentially attached. Global deprotection eventually afforded the
      sperm CD52 GPI. The method may be useful for the synthesis of other GPIs having
      an acylated inositol.

PMID- 14692776
TI  - A superoxo-ferrous state in a reduced oxy-ferrous hemoprotein and model
      compounds.
AB  - Cryoreduction of the [FeO2]6 (n = 6 is the number of electrons in 3d orbitals on
      Fe and pi* orbitals on O2) dioxygen-bound ferroheme through irradiation at 77 K
      generates an [FeO2]7 reduced oxy-heme. Numerous investigations have examined
      [FeO2]7 centers that have been characterized as peroxo-ferric centers, denoted
      [FeO2]per7, in which a ferriheme binds a dianionic peroxo-ligand. The generation
      of such an intermediate can be understood heuristically if the [FeO2]6 parent is
      viewed as a superoxo-ferric center and the injected electron localizes on the O-O
      moiety. We here report EPR/ENDOR experiments which show quite different
      properties for the [FeO2]7 centers produced by cryoreduction of monomeric oxy
      hemoglobin (oxy-GMH3) from Glycera dibranchiata, which is unlike mammalian
      "globins" in having a leucine in place of the distal histidine; of frozen aprotic
      solutions of oxy-ferrous octaethyl porphyrin; and of the oxy-ferrous complex of
      the heme model, cyclidene. These [FeO2]7 centers are characterized as "superoxo
      ferrous" centers ([FeO2]sup7), with nearly unit spin density localized on a
      superoxo moiety which is end-on coordinated to a low-spin ferrous ion. This
      assignment is based on their g tensors and 17O hyperfine couplings, which are
      characteristic of the superoxide ion coordinated to a diamagnetic metal ion, and
      on the absence of detectable ENDOR signals either from the in-plane 14N ligands
      or from an exchangeable H-bond proton. Such a center would arise if the electron
      that adds to the [FeO2]6 superoxo-ferric parent localizes on the Fe ion, to make
      a superoxo-ferrous moiety. Upon annealing to T > 150 K, the [FeO2]sup7 species
      converts to peroxo/hydroperoxo-ferric ([FeO2H]7) intermediates. These experiments
      suggest that the primary reduction product is [FeO2]sup7 and that the internal
      redox transition to [FeO2]per7/[FeO2H]7 states is driven at least in part by H
      bonding/proton donation by the environment.

PMID- 14692777
TI  - Trans influence on the rate of reductive elimination. Reductive elimination of
      amines from isomeric arylpalladium amides with unsymmetrical coordination
      spheres.
AB  - To determine the trans effect on the rates of reductive eliminations from
      arylpalladium(II) amido complexes, the reactions of arylpalladium amido complexes
      bearing symmetrical and unsymmetrical DPPF (DPPF =
      bis(diphenylphosphino)ferrocene) derivatives were studied. THF solutions of
      LPd(Ar)(NMeAr') (L = DPPF, DPPF-OMe, DPPF-CF3, DPPF-OMe,Ph, DPPF-Ph,CF3, and DPPF
      OMe,CF3; Ar = C6H4-4-CF3; Ar' = C6H4-4-CH3, Ph, and C6H4-4-OMe) underwent C-N
      bond forming reductive elimination at -15 C to form the corresponding N
      methyldiarylamine in high yield. Complexes ligated by symmetrical DPPF
      derivatives with electron-withdrawing substituents on the DPPF aryl groups
      underwent reductive elimination faster than complexes ligated by symmetrical DPPF
      derivatives with electron-donating substituents on the ligand aryl groups.
      Studies of arylpalladium amido complexes containing unsymmetrical DPPF ligands
      revealed several trends. First, the complex with the weaker donor trans to
      nitrogen and the stronger donor trans to the palladium-bound aryl group underwent
      reductive elimination faster than the regioisomeric complex with the stronger
      donor trans to nitrogen and the weaker donor trans to the palladium-bound aryl
      group. Second, the effect of varying the substituents on the phosphorus donor
      trans to the nitrogen was larger than the effect of varying the substituents on
      the phosphorus donor trans to the palladium-bound aryl group. Third, the
      difference in rate between the isomeric arylpalladium amido complexes was similar
      in magnitude to the differences in rates resulting from conventional variation of
      substituents on the symmetric phosphine ligands. This result suggests that the
      geometry of the complex is equal in importance to the donating ability of the
      dative ligands. The ratio of the differences in rates of reaction of the isomeric
      complexes was similar to the relative populations of the two geometric isomers.
      This result and consideration of transition state geometries suggest that the
      reaction rates are controlled more by substituent effects on ground state
      stability than on transition state energies. In addition, variation of the aryl
      group at the amido nitrogen showed systematically that complexes with more
      electron-donating groups at nitrogen undergo faster reductive elimination than
      those with less electron-donating groups at nitrogen.

PMID- 14692778
TI  - Chemical compounds formed from diacetylene and rare-gas atoms: HKrC4H and HXeC4H.
AB  - New organic rare-gas compounds, HRgC4H (Rg = Kr or Xe), are identified in matrix
      isolation experiments supported by ab initio calculations. These compounds are
      the largest molecules among the known rare-gas hydrides. They are prepared in low
      temperature rare-gas matrixes via UV photolysis of diacetylene and subsequent
      thermal mobilization of H atoms at approximately 30 and 45 K for Kr and Xe,
      respectively. The strongest IR absorption bands of the HRgC4H molecules are the H
      Rg stretches with the most intense components at 1290 cm(-1) for HKrC4H and at
      1532 cm(-1) for HXeC4H, and a number of weaker absorptions (C-H stretching, C-C-C
      bending, and C-C-H bending modes) are also found in agreement with the
      theoretical predictions. As probably the most important result, the IR absorption
      spectra indicate some further stabilization of the HRgC4H molecules as compared
      with the corresponding HRgC2H species identified recently (Khriachtchev et al. J.
      Am. Chem. Soc. 2003, 125, 4696 and Khriachtchev et al. J. Am. Chem. Soc. 2003,
      125, 6876). The computational energetic results support this trend. HXeC4H is
      predicted to be 2.5 eV lower in energy than H + Xe + C4H, which is approximately
      1 eV larger than the corresponding value for HXeC2H. We expect that the larger
      molecules HRgC6H and HRgC8H are even more stable and the HRgC2nH species are good
      candidates for bulk organic rare-gas material.

PMID- 14692779
TI  - Ruthenacarboranes from the reaction of nido-1,2-(Cp*RuH)2B3H7 with HC [triple
      bond] CCO2Me, Cp* = eta5-C5Me5. Hydrometalation, alkyne incorporation, and
      functional group modification via cooperative metal-boron interactions within a
      metallaborane cluster framework.
AB  - Reaction of nido-1,2-(Cp*RuH)2B3H7, 1, and methyl acetylene monocarboxylate under
      kinetic control generates nido-1,2-(Cp*Ru)2(mu-C[[CO2Me]Me])B3H7 (a pair of
      geometric isomers, 3 and 5) and nido-1,2-(Cp*Ru)2(1,3-mu-C[[CH2CO2Me]H])B3H7, 4,
      which display the first examples of exo-cluster mu-alkylidene Ru-B bridges
      generated by hydrometalation of an alkyne on the cluster framework. Both 3 and 5,
      but not 4, rearrange into arachno-2,8-mu(C)-5-eta1(O)-Me[CO2Me]C-1,2
      (Cp*Ru)2B3H7, 2, in which an unprecedented intramolecular coordination of the
      carbonyl oxygen atom of the alkyne substituent to a boron framework site opens
      the ruthenaborane skeleton. Compound 2, in turn, is an intermediate in the
      formation of the ruthenacarborane nido-1,2-(Cp*Ru)2-3-OH-4-OMe-5-Me-4,5-C2B2H5,
      12, in which the carbonyl-oxygen double bond has been cleaved as its oxygen atom
      inserts into a B-H bond and the carbonyl carbon inserts into the metallaborane
      framework. In a parallel reaction pathway, nido-1,2-(Cp*Ru)2-5-CO2Me-4,5-C2B2H7,
      6, nido-1,2-(Cp*Ru)2-4-B(OH)2-5-CO2Me-4,5-C2B2H6, 16, and nido-1,2-(Cp*Ru)2(mu
      H)(mu-BH2)-3-(CH2)2CO2Me-CO2Me-4,5-C2B2H4 (a pair of geometric isomers, 7 and 14,
      which contain an unusual Ru-B borane bridge) are formed. On heating, 7 rearranges
      to yield nido-1,2-(Cp*Ru)2-3-(CH2)2CO2Me-4-BH2-5-CO2Me-4,5-C2B2H5, 13, whereas 14
      converts to nido-1,2-(Cp*Ru)2-3-(CH2)2CO2Me-4-CO2Me-4,5-C2B2H6, 8. Under
      thermodynamic control, nido-1,2-(Cp*Ru)2-4,5-B[(CH2)2CO2Me]CO(MeO)[C(CH2)CO2Me]
      4,5-C2B2H6, 11, is the major product accompanied by lesser amounts of 6 and 1,2
      (Cp*Ru)2-4-OMe-5-Me-4,5-C2B2H6, 10. Compound 11 features a five-membered
      heterocycle containing a boron atom. The structure of 7, which is an intermediate
      in the formation of 11, provides the basis for an explanation of this complex
      condensation of three alkynes. A previously unrecognized role for an exo-cluster
      bridging borene generated from the metallaborane skeleton by addition of the
      alkyne is also a feature of this chemistry. Reinsertion or loss of this boron
      fragment accounts for much of the chemistry observed. NMR experiments reveal
      labile intermediates, and one has been sufficiently characterized to provide
      mechanistic insight on the early stages of the alkyne-metallaborane addition
      reaction. All isolated compounds have been spectroscopically characterized, and
      most have been structurally characterized in the solid state.

PMID- 14692780
TI  - Beta-sheet preferences from first principles.
AB  - The natural amino acids have different preferences of occurring in specific types
      of secondary protein structure. Simulations are performed on periodic model beta
      sheets of 14 different amino acids, at the level of density functional theory,
      employing the generalized gradient approximation. We find that the statistically
      observed beta-sheet propensities correlate very well with the calculated binding
      energies. Analysis of the calculations shows that the beta-sheet propensities are
      determined by the local flexibility of the individual polypeptide strands.

PMID- 14692781
TI  - A density functional theory investigation of Fe-N-O bonding in heme proteins and
      model systems.
AB  - We report the results of a series of density functional theory (DFT) calculations
      of the Mossbauer quadrupole splittings and isomer shifts in NO heme model
      compounds, together with the results of calculations of the Mossbauer quadrupole
      splittings, isomer shifts, and electron paramagnetic resonance hyperfine coupling
      constants in a model Fe(II)(NO)(imidazole) complex as a function of Fe-NO bond
      length and Fe-N-O bond angle. The results of the Mossbauer quadrupole splitting
      and isomer shift calculations on the NO heme model compounds show good accord
      between theory and experiment, with the largest errors being observed for
      structures having the largest crystallographic R(1) values. The results of the
      property surface calculations were then used to calculate Fe-NO bond length and
      Fe-N-O bond angle probability surfaces (Z-surfaces) for a nitrosyl hemoglobin,
      using, in addition, an energy filter. The results obtained yielded a most
      probable Fe-NO bond length (r) of 1.79 A and an Fe-N-O bond angle (beta) of 136
      degrees -137 degrees. This bond length is somewhat longer than those observed in
      most model compounds but may be due, at least in part, to hydrogen bond formation
      with the distal His residue. Bond elongation was also observed in a geometry
      optimized Fe(II)(NO)(imidazole) complex hydrogen bonded to an imidazole residue,
      in which we find r = 1.76-1.78 A and beta = 137 degrees -138 degrees. The
      computed bond angles are close to the canonical approximately 140 degrees value
      found in most model systems. Highly bent Fe-N-O bond angles or very long Fe-NO
      bond lengths seem unlikely to occur in proteins, due to their high energies. We
      also investigated the molecular orbitals and spin densities in each of the six
      coordinate systems investigated and found the orbitals and spin densities to be
      generally similar those described previously for five coordinate systems. Taken
      together, these results show that Mossbauer quadrupole splittings and isomer
      shifts, in addition to electron paramagnetic resonance hyperfine coupling
      constants, can now be calculated for nitrosyl heme systems with relatively good
      accuracy and that the results so obtained can be used to determine Fe-N-O
      geometries in metalloproteins. The Z-surface approach is thus applicable to both
      diamagnetic (CO) and paramagnetic (NO) heme proteins with in both cases the metal
      ligand binding geometries found in the proteins being very close to those seen in
      model systems.

PMID- 14692782
TI  - Nonplanarity at tri-coordinated aluminum and gallium: cyclic structures for
      X3Hn(m) (X = B, Al, Ga).
AB  - Structures and energies of X3H3(2-), X3H4-, X3H5, and X3H6+ (X = B, Al and Ga)
      were investigated theoretically at B3LYP/6-311G(d) level. The global minimum
      structures of B are not found to be global minima for Al and Ga. The hydrides of
      the heavier elements Al and Ga have shown a total of seven, six and eight minima
      for X3H3(2-), X3H(4-), and X3H5, respectively. However, X3H(6+) has three and
      four minima for Al and Ga, respectively. The nonplanar arrangements of hydrogens
      with respect to X3 ring is found to be very common for Al and Ga species.
      Similarly, species with lone pairs on heavy atoms dominate the potential energy
      surfaces of Al and Ga three-ring systems. The first example of a structure with
      tri-coordinate pyramidal arrangement at Al and Ga is found in X3H(4-) (2g),
      contrary to the conventional wisdom of C3H3+, B3H3, etc. The influence of pi
      delocalization in stabilizing the structures decreases from X3H3(2-) to X3H6+ for
      heavier elements Al and Ga. In general, minimum energy structures of X3H4-, X3H5,
      and X3H6+ may be arrived at by protonating the minimum energy structures
      sequentially starting from X3H3(2-). The resonance stabilization energy (RSE) for
      the global minimum structures (or nearest structures to global minimum which
      contains pi-delocalization) is computed using isodesmic equations.

PMID- 14692783
TI  - NMR study on the photoresponsive DNA tethering an azobenzene. Assignment of the
      absolute configuration of two diastereomers and structure determination of their
      duplexes in the trans-form.
AB  - Two diastereomers of a photoresponsive oligodeoxyribonucleotide tethering a trans
      azobenzene, based on the chirality of the central carbon of a diol linker, were
      separated by reversed-phase HPLC. On the basis of 2D NMR analysis, absolute
      configurations of the diastereomers alpha and beta (tentatively designated from
      differences in their retention time) were determined as R- and S-forms,
      respectively. For both diastereomers, their NMR-determined duplex structure
      showed that trans-azobenzene intercalates between base pairs, because distinct
      NOEs were observed between the protons of azobenzene and those of the adjacent
      base pairs, such as with the imino protons and methyl protons of thymine. The
      melting temperatures of both duplexes were higher than that of the corresponding
      native duplex, which contained no azobenzene residue, due to the intercalated
      trans-azobenzene stabilizing the duplex by a stacking interaction. Between these
      two diastereomers, differences in T(m) were also found: the melting temperature
      of the R-form duplex (alpha-isomer) was higher than that of the S-form (beta
      isomer). On the basis of the NMR-determined structure, this difference was
      attributed to the fact that the S-form (beta isomer) causes more stress forming
      the duplex than does the R-form (alpha isomer) due to disturbances of the right
      hand helix.

PMID- 14692784
TI  - Determination of the active site protonation state of beta-secretase from
      molecular dynamics simulation and docking experiment: implications for structure
      based inhibitor design.
AB  - Memapsin 2 (BACE) is an aspartyl protease known as beta-secretase that acts on
      the production of the beta-amyloid peptide in the human brain, a key event in the
      pathogenesis of Alzheimer's disease. Although it is expected that the net charge
      of the catalytic Asp diad would be -1 as in other kinds of aspartyl proteases,
      the exact protonation states of Asp32 and Asp228 have not been known without
      ambiguity. Two independent molecular dynamics (MD) simulations of BACE in complex
      with the potent inhibitor OM99-2 are carried out to determine the preferred
      protonation state of the Asp diad in the context that is consistent with the
      previous X-ray crystal structure. The results show that a strong hydrogen bond
      between the inhibitor hydroxyl group and Asp228 can be maintained only when Asp32
      is neutral and Asp228 is ionized. The preference of this protonation state is
      further supported from the energetic and structural features found in the docking
      experiment of a novel potent inhibitor with the BACE active site. Thus, both MD
      and docking studies suggest that the role of hydrogen bond acceptor for the
      hydroxyl and piperazine groups of the inhibitors should be played by Asp228
      instead of Asp32. This may be a key piece of information for the structure-based
      design/discovery of new inhibitor drugs.

PMID- 14692785
TI  - 13C direct detection experiments on the paramagnetic oxidized monomeric copper,
      zinc superoxide dismutase.
AB  - In this report, the use of 13C direct detection has been pursued in 2D
      experiments (13C-13C COSY, 13C-13C COCAMQ, 13C-13C NOESY) to detect broad lines
      in nuclear magnetic resonance spectra of paramagnetic metalloproteins. The sample
      is a monomeric oxidized copper, zinc superoxide dismutase. Thanks to direct
      detection probeheads, cryogenic technology, and implementation of 13C band
      selective homodecoupling, many broadened signals were detected. Proton signals
      for the same residues escaped detection in 1H and 1H-15N HSQC experiments because
      of the broadening. Only the 13C signals which experience large contact coupling
      escaped detection, i.e., the 13C nuclei of the metal coordinated histidines.
      Otherwise, nuclei as close to copper(II) as 4 A can be detected. Paramagnetic
      based restraints can in principle be used for solution structure determination of
      paramagnetic metalloproteins and in copper(II) proteins in particular. The
      present study is significant also for the study of large diamagnetic proteins for
      which proton relaxation makes proton-based spectroscopy not adequate.

PMID- 14692786
TI  - Phase switching of a single isomeric molecule and associated characteristic
      rectification.
AB  - Variations in molecular electronic structures related to conformational change
      are exceedingly attractive because of their key role in the understanding and
      development of functional processes in molecular electronics and biology. We
      observed, for the first time, the novel phase switching of a photoactive isomeric
      molecule, N-(2-mercaptoethyl)-4-phenylazobenzamide (Azo molecule) at a single
      molecule level, which exhibits a distinctive change in the conductive
      characteristic under scanning tunneling microscope (STM) measurement. In
      comparison with the results obtained by the measurement of photoactive
      isomerization of the isolated Azo molecule, which was performed also for the
      first time, the observed characteristics are attributed to the results of the
      trans and cis phase transformation of the Azo molecule, under the condition of an
      external electric field and current flow. A specific point is that the potential
      landscape of the system is controllable by the electric field and provides a
      conformational stability with asymmetric bias dependence resulting in
      rectification.

PMID- 14692787
TI  - A nonempirical anisotropic atom-atom model potential for chlorobenzene crystals.
AB  - A nearly nonempirical, transferable model potential is developed for the
      chlorobenzene molecules (C6ClnH6-n, n = 1 to 6) with anisotropy in the atom-atom
      form of both electrostatic and repulsion interactions. The potential is largely
      derived from the charge densities of the molecules, using a distributed multipole
      electrostatic model and a transferable dispersion model derived from the
      molecular polarizabilities. A nonempirical transferable repulsion model is
      obtained by analyzing the overlap of the charge densities in dimers as a function
      of orientation and separation and then calibrating this anisotropic atom-atom
      model against a limited number of intermolecular perturbation theory calculations
      of the short-range energies. The resulting model potential is a significant
      improvement over empirical model potentials in reproducing the twelve
      chlorobenzene crystal structures. Further validation calculations of the lattice
      energies and rigid-body k = 0 phonon frequencies provide satisfactory agreement
      with experiment, with the discrepancies being primarily due to approximations in
      the theoretical methods rather than the model intermolecular potential. The
      potential is able to give a good account of the three polymorphs of p
      dichlorobenzene in a detailed crystal structure prediction study. Thus, by
      introducing repulsion anisotropy into a transferable potential scheme, it is
      possible to produce a set of potentials for the chlorobenzenes that can account
      for their crystal properties in an unprecedentedly realistic fashion.

PMID- 14692788
TI  - Electron transfer and singlet oxygen mechanisms in the photooxygenation of
      dibutyl sulfide and thioanisole in MeCN sensitized by N-methylquinolinium
      tetrafluoborate and 9,10-dicyanoanthracene. The probable involvement of a
      thiadioxirane intermediate in electron transfer photooxygenations.
AB  - Photooxygenations of PhSMe and Bu2S sensitized by N-methylquinolinium (NMQ+) and
      9,10-dicyanoanthracene (DCA) in O2-saturated MeCN have been investigated by laser
      and steady-state photolysis. Laser photolysis experiments showed that excited
      NMQ+ promotes the efficient formation of sulfide radical cations with both
      substrates either in the presence or in absence of a cosensitizer (toluene). In
      contrast, excited DCA promotes the formation of radical ions with PhSMe, but not
      with Bu2S. To observe radical ions with the latter substrate, the presence of a
      cosensitizer (biphenyl) was necessary. With Bu2S, only the dimeric form of the
      radical cation, (Bu2S)2+*, was observed, while the absorptions of both PhSMe+*
      and (PhSMe)2+* were present in the PhSMe time-resolved spectra. The decay of the
      radical cations followed second-order kinetics, which in the presence of O2, was
      attributed to the reaction of the radical cation (presumably in the monomeric
      form) with O2-* generated in the reaction between NMQ* or DCA-* and O2. The
      fluorescence quenching of both NMQ+ and DCA was also investigated, and it was
      found that the fluorescence of the two sensitizers is efficiently quenched by
      both sulfides (rates controlled by diffusion) as well by O2 (kq = 5.9 x 10(9) M(
      1) s(-1) with NMQ+ and 6.8 x 10(9) M(-1) s(-1) with DCA). It was also found that
      quenching of 1NMQ* by O2 led to the production of 1O2 in significant yield
      (PhiDelta = 0.86 in O2-saturated solutions) as already observed for 1DCA*. The
      steady-state photolysis experiments showed that the NMQ+- and DCA-sensitized
      photooxygenation of PhSMe afford exclusively the corresponding sulfoxide. A
      different situation holds for Bu2S: with NMQ+, the formation of Bu2SO was
      accompanied by that of small amounts of Bu2S2; with DCA, the formation of Bu2SO2
      was also observed. It was conclusively shown that with both sensitizers, the
      photooxygenations of PhSMe occur by an electron transfer (ET) mechanism, as no
      sulfoxidation was observed in the presence of benzoquinone (BQ), which is a trap
      for O2-*, NMQ*, and DCA-*. BQ also suppressed the NMQ+-sensitized
      photooxygenation of Bu2S, but not that sensitized by DCA, indicating that the
      former is an ET process, whereas the second proceeds via singlet oxygen. In
      agreement with the latter conclusion, it was also found that the relative rate of
      the DCA-induced photooxygenation of Bu2S decreases by increasing the initial
      concentration of the substrate and is slowed by DABCO (an efficient singlet
      oxygen quencher). To shed light on the actual role of a persulfoxide intermediate
      also in ET photooxygenations, experiments in the presence of Ph2SO (a trap for
      the persulfoxide) were carried out. Cooxidation of Ph2SO to form Ph2SO2 was,
      however, observed only in the DCA-induced photooxygenation of Bu2S, in line with
      the singlet oxygen mechanism suggested for this reaction. No detectable amounts
      of Ph2SO2 were formed in the ET photooxygenations of PhSMe with both DCA and NMQ+
      and of Bu2S with NMQ+. This finding, coupled with the observation that 1O2 and ET
      photooxygenations lead to different product distributions, makes it unlikely
      that, as currently believed, the two processes involve the same intermediate,
      i.e., a nucleophilic persulfoxide. Furthermore, the cooxidation of Ph2SO observed
      in the DCA-induced photooxygenation of Bu2S was drastically reduced when the
      reaction was performed in the presence of 0.5 M biphenyl as a cosensitizer, that
      is, under conditions where an (indirect) ET mechanism should operate. This
      observation confirms that a persulfoxide is formed in singlet oxygen but not in
      ET photosulfoxidations. The latter conclusion was further supported by the
      observation that also the intermediate formed in the reaction of thianthrene
      radical cation with KO2, a reaction which mimics step d (Scheme 2) in the ET
      mechanism of photooxygenation, is an electrophilic species, being able to oxidize
      Ph2S but not Ph2SO. It is thus proposed that the intermediate involved in ET
      sulfoxidations is a thiadioxirane, whose properties (it is an electrophilic
      species) seem more in line with the observed chemistry. Theoretical calculations
      concerning the reaction of a sulfide radical cation with O2-* provide a rationale
      for this proposal.

PMID- 14692789
TI  - Insights into the structure of cyclohexane from femtosecond degenerate four-wave
      mixing spectroscopy and ab initio calculations.
AB  - In this paper, we report the use of femtosecond time-resolved degenerate four
      wave mixing rotationally resolved spectroscopy to obtain very accurate structural
      information on the symmetric top cyclohexane. Apart from highlighting the
      versatility of this method in determining accurate structures of large and
      complex molecules without dipole moment, the present study also details the
      comparison of the experimentally determined rotational constant B(0) with that
      obtained from high-level ab initio calculations. The theoretical calculations,
      which were carried out at both the second-order Moller-Plesset (MP2) and coupled
      cluster with single, double, and perturbative triple substitutions [CCSD(T)]
      levels of theory, also take into account vibrational averaging effects. A
      detailed investigation of the vibrational averaging effects reveals that the
      corrections emerge from only the six highly symmetric A(1g) modes, a
      justification of which is provided by an analysis of these modes.

PMID- 14692792
TI  - Influence of spermine on DNA conformation in a molecular dynamics trajectory of
      d(CGCGAATTCGCG)(2): major groove binding by one spermine molecule delays the A-
      >B transition.
AB  - The effect of spermine on the A-DNA to B-DNA transition in d(CGCGAATTCGCG)(2) has
      been investigated by five A-start molecular dynamics simulations, using the
      Cornell et al. potential. In the absence of spermine an A-->B transition is
      initiated immediately and the DNA becomes equidistant from the A- and B-forms at
      200ps. In three DNA-spermine simulations, when a spermine is located across the
      major groove of A-DNA in one of three different initial locations, the time taken
      to reach equidistance from the A- and B-forms is delayed until 800, 950 or
      1000ps. In each case the A-form appears to be temporarily stabilized by
      spermine's electrostatic interactions with phosphates on both sides of the major
      groove. The onset of the A-->B transition can be correlated with the spermine
      losing contact with phosphates on one side of the groove and with A-like --> B
      like sugar pucker transitions in the vicinity of the spermine bridge. However in
      the fifth trajectory, in which the spermine initially threads from the major
      groove via the backbone into the minor groove, the B-->A transition occurs
      rapidly once again and the DNA is equidistant between the A- and B-forms within
      300ps. This indicates that the mere presence of spermine is insufficient to delay
      the transition and that major groove binding stabilizes A-DNA.

PMID- 14692793
TI  - Discrimination between BI and BII conformational substates of B-DNA based on
      sugar-base interproton distances.
AB  - Molecular dynamics (MD) simulations of four water-solvated DNA duplexes were used
      to generate a database of approximately 27000 dinucleotide conformations.
      Analyzing this database, we investigated the relationship between so-called BI
      BII transitions and short-range interproton distances. Four H-H distances were
      found particularly sensitive to BI-BII transitions: internucleotide H1'(n)
      H68(n+1), H2'(n)-H68(n+1), and H2"(n)-H68(n+1), and intranucleotide H2"(n)
      H68(n). Determination of these distances using classical NOESY spectroscopy can
      thus provide valuable indications on the existence of BII substates,
      complementing the existing method based on (31)P chemical shifts and (31)P-(1)H
      spin-spin coupling constants.

PMID- 14692794
TI  - The influence of a chiral amino acid on the helical handedness of PNA in solution
      and in crystals.
AB  - The X-ray structure of a self-complementary PNA hexamer (H-CGTACG-L-Lys-NH(2))
      has been determined to 2.35 A resolution. The introduction of an L-lysine moiety
      has previously been shown to induce a preferred left-handedness of the PNA double
      helices in aqueous solution. However, in the crystal structure an equal amount of
      interchanging right- and left-handed helices is observed. The lysine moieties are
      pointing into large solvent channels and no significant interactions between this
      moiety and the remaining PNA molecule are observed. In contrast, molecular
      mechanics calculations show a preference for the left-handed helix of this
      hexameric PNA in aqueous solution as expected. The calculations indicate that the
      difference in the free energy of solvation between the left-handed and the right
      handed helix is the determining factor for the preference of the left-handed
      helix in aqueous solution.

PMID- 14692795
TI  - Stability and transformations of bis-PNA/DNA triplex structural isomers.
AB  - Structurally isomeric complexes formed between homopyrimidine bis-PNAs
      (T(2)JT(2)JT(4)-linker-T(4)CT(2)CT(2)) and single- and double-stranded DNA
      targets were investigated. These complexes are triplexes designated S1, S2 and S3
      in order of increased mobility by polyacrylamide gel electrophoresis. It is shown
      that the S3 isomer is formed only on double-stranded DNA and possesses highest
      stability. Isomers S2 and S1 are formed upon binding of bis-PNA to double
      stranded as well as to single-stranded DNA. It was found that the stability of
      the isomer S1 increases dramatically in the presence of excess single-stranded
      oligonucleotide complementary to the bis-PNA. The structure of the stabilized S1
      isomer is proposed to consist of two bis-PNA/DNA triplexes. The relationship
      between the yield of the isomer S1 formed on single-stranded DNA and the bis-PNA
      concentration was investigated and a kinetic model of the formation of S1 is
      presented.

PMID- 14692796
TI  - Engineering a thermostable protein with two DNA-binding domains using the
      hyperthermophile protein Sac7d.
AB  - The acid- and thermostable Sac7d is a small, non-specific DNA-binding protein of
      the hyperthermophile archaea Sulfolobus acidocaldarius. In this study, Sac7d was
      employed as a structural unit in the design of a thermostable protein containing
      two putative DNA-binding domains. By linking two Sac7d proteins together and
      comparing the DNA interaction of dimer to that of monomer, this study may provide
      structural insights into other dimeric DNA-binding proteins. The engineered
      protein, Sac7dK66C, was over-expressed and purified. Dimeric Sac7d was obtained
      by cross-linking two mutant Sac7d molecules through the C-terminal disulfide
      bond. Thermal stability and DNA-binding ability of dimeric Sac7d were assessed
      and compared to those of wild type Sac7d by gel retardation assay, circular
      dichroism spectroscopy, and crystallization experiments. Dimeric Sac7d was shown
      to be equally thermostable as wild type, and its ability to stabilize DNA duplex
      is the same as wild type. However, the interaction of dimeric Sac7d with DNA
      diverged from that of wild type, suggesting different DNA-binding modes for
      dimeric Sac7d. In addition, a large difference in extinction coefficient was
      observed in all dimer/DNA CD spectra, which was reminiscent of the spectrum of
      Psi-DNA. Conjugation of various chemical groups to mutant Sac7d is possible
      through the C-terminal thiol group. This offers a possible approach in the design
      of a thermostable biomolecule with novel functions.

PMID- 14692797
TI  - Synonymous codon usage in Lactococcus lactis: mutational bias versus
      translational selection.
AB  - In this study codon usage bias of all experimentally known genes of Lactococcus
      lactis has been analyzed. Since Lactococcus lactis is an AT rich organism, it is
      expected to occur A and/or T at the third position of codons and detailed
      analysis of overall codon usage data indicates that A and/or T ending codons are
      predominant in this organism. However, multivariate statistical analyses based
      both on codon count and on relative synonymous codon usage (RSCU) detect a large
      number of genes, which are supposed to be highly expressed are clustered at one
      end of the first major axis, while majority of the putatively lowly expressed
      genes are clustered at the other end of the first major axis. It was observed
      that in the highly expressed genes C and T ending codons are significantly higher
      than the lowly expressed genes and also it was observed that C ending codons are
      predominant in the duets of highly expressed genes, whereas the T endings codons
      are abundant in the quartets. Abundance of C and T ending codons in the highly
      expressed genes suggest that, besides, compositional biases, translational
      selection are also operating in shaping the codon usage variation among the genes
      in this organism as observed in other compositionally skewed organisms. The
      second major axis generated by correspondence analysis on simple codon counts
      differentiates the genes into two distinct groups according to their
      hydrophobicity values, but the same analysis computed with relative synonymous
      codon usage values could not discriminate the genes according to the hydropathy
      values. This suggests that amino acid composition exerts constraints on codon
      usage in this organism. On the other hand the second major axis produced by
      correspondence analysis on RSCU values differentiates the genes into two groups
      according to the synonymous codon usage for cysteine residues (rarest amino acids
      in this organism), which is nothing but a artifactual effect induced by the RSCU
      values. Other factors such as length of the genes and the positions of the genes
      in the leading and lagging strand of replication have practically no influence in
      the codon usage variation among the genes in this organism.

PMID- 14692798
TI  - Conformational analysis of canonical 2-deoxyribonucleotides. 1. Pyrimidine
      nucleotides.
AB  - The molecular structure and relative stability of north and south conformers of
      2'-deoxyribonucleotides containing pyrimidine nucleic acid bases ( 2'
      deoxythymidilic (pdT), 2'-deoxycytidilic (pdC) acids and their mono- and
      dianions) have been obtained and analyzed at the DFT/B3LYP level using the
      standard 6-31G(d) basis set. We have revealed that, when the nucleobase moiety is
      incorporated into the nucleotides, it maintains a nonplanar and nonrigid
      conformation due to out-of-plane deformation of the amino group and pyrimidine
      ring. It has been demonstrated that an increase of negative charge of the
      phosphate group results in increase of amino group pyramidalization,
      discrimination between conformers with syn and anti orientation of base with
      respect to sugar, strengthening of intramolecular C-H.O hydrogen bonds leading to
      deformation and fixation of geometry of nucleotides, and weakening of
      phosphodiester bond. These results allow to make suggestions about sources of
      twist and buckle deformations of base pairs, mechanisms of repaire of DNA via
      change of base orientation, and conditions for breakage of the P-O bonds during
      hydrolysis.

PMID- 14692799
TI  - Molecular dynamics simulations of peptides from the central domain of smooth
      muscle caldesmon.
AB  - The central domain of smooth muscle caldesmon contains a highly charged region
      consisting of ten 13-residue repeats. Experimental evidence obtained from the
      intact protein and fragments thereof suggests that this entire region forms a
      single stretch of stable alpha-helix. We have carried out molecular dynamics
      simulations on peptides consisting of one, two and three repeats to examine the
      mechanism of alpha-helical stability of the central domain at the atomic level.
      All three peptides show high helical stability on the timescale of the MD
      simulations. Deviations from alpha-helical structure in all the simulations arise
      mainly from the formation of long stretches of pi-helix. Interconversion between
      alpha-helical and pi-helical conformations occurs through insertion of water
      molecules into alpha-helical hydrogen bonds and subsequent formation of reverse
      turns. The alpha-helical structure is stabilized by electrostatic interactions
      (salt bridges) between oppositely charged sidechains with i,i+4 spacings, while
      the pi-helix is stabilized by i,i+5 salt bridge interactions. Possible i,i+3 salt
      bridges are of minor importance. There is a strong preference for salt bridges
      with a Glu residue N-terminal to a basic sidechain as compared to the opposite
      orientation. In the double and triple repeat peptides, strong i,i+4 salt bridges
      exist between the last Glu residue of one repeat and the first Lys residue of the
      next. This demonstrates a relationship between the repetitive nature of the
      central domain sequence and its ability to form very long stretches of alpha
      helical structure.

PMID- 14692800
TI  - PFG-NMR investigations of the binding of cationic neuropeptides to anionic and
      zwitterionic micelles.
AB  - The mechanism by which peptides bind to micelles is believed to be a two-phase
      process, involving (i). initial electrostatic interactions between the peptide
      and micelle surface, followed by (ii). hydrophobic interactions between peptide
      side chains and the micelle core. To better characterize the electrostatic
      portion of this process, a series of pulse field gradient nuclear magnetic
      resonance (PFG-NMR) spectroscopic experiments were conducted on a group of
      neuropeptides with varying net cationic charges (+1 to +3) and charge location to
      determine both their diffusion coefficients and partition coefficients when in
      the presence of detergent micelles. Two types of micelles were chosen for the
      study, namely anionic sodium dodecylsulfate (SDS) and zwitterionic
      dodecylphosphocholine (DPC) micelles. Results obtained from this investigation
      indicate that in the case of the anionic SDS micelles, peptides with a larger net
      positive charge bind to a greater extent than those with a lesser net positive
      charge (bradykinin > substance P > neurokinin A > Met-enkephalin). In contrast,
      when in the presence of zwitterionic DPC micelles, the degree of mixed-charge
      nature of the peptide affects binding (neurokinin A > substance P > Met
      enkephalin > bradykinin). Partition coefficients between the peptides and the
      micelles follow similar trends for both micelle types. Diffusion coefficients for
      the peptides in SDS micelles, when ranked from largest to smallest, follow a
      trend where increasing net positive charge results in the smallest diffusion
      coefficient: Met-enkephalin > neurokinin A > bradykinin > substance P. Diffusion
      coefficients when in the presence of DPC micelles, when ranked from largest to
      smallest, follow a trend where the presence of negatively-charged side chains
      results in the smallest diffusion coefficient: bradykinin > Met-enkephalin >
      substance P > neurokinin A.

PMID- 14692801
TI  - 3D structure model of the principal neutralizing epitope of Minnesota HIV-1
      isolate.
AB  - A hierarchical procedure, using a "bottom-up" strategy and combining (i). a
      probabilistic approach for estimating all possible starting structures, (ii).
      restrained molecular mechanics algorithms for preliminary selection of all
      energetically preferred conformers, as well as (iii). quantum chemical
      computations for refining their geometry, was used to study the structural
      properties of the HIV-MN neutralizing epitope in terms of NMR spectroscopy data.
      As a result, only one of initial structures matching the experimental and
      theoretical data was found to be well-ground for implementing the function of
      immunoreactive conformation of the virus immunogenic crown. The geometric
      parameters of this structure in water solution were shown to correspond to a
      double beta-turn conformation similar to that revealed in crystal for synthetic
      molecules imitating the central region of the HIV-MN V3 loop. The following
      conclusion was drawn from the comparative analysis of simulated structure with
      the one computed previously: the HIV-MN immunogenic tip has some inherent
      conformational flexibility that manifests at the alterations of hexapeptide
      environment and leads to the structural transitions changing the local
      conformation of the stretch of interest but retaining its spatial main chain
      fold. As a matter of record, the high resolution 3D structure model for the HIV
      MN principal neutralization site was constructed, and its geometric parameters
      were compared with the corresponding characteristics of conformers derived
      earlier for describing the conformational features of immunogenic tip of gp120
      from Thailand HIV-1 isolate.

PMID- 14692802
TI  - Monosialogangliosides and their interaction with cholera toxin - investigation by
      molecular modeling and molecular mechanics.
AB  - Molecular mechanics and molecular dynamics studies are performed to investigate
      the conformational preference of cell surface monosialogangliosides (GM3, GM2 and
      GM1) in aqueous environment. Water mediated hydrogen bonding network plays a
      significant role in the structural stabilization of GM3, GM2 and GM1. The spatial
      flexibility of NeuNAc of gangliosides at the binding site of cholera toxin
      reveals a limited allowed eulerian space of 2.4% with a much less allowed
      eulerian space (1.4%) for external galactose of GM1. The molecular mechanics of
      monosialoganglioside-cholera toxin complex reveals that cholera toxin can
      accommodate the monosialogangliosides in three different modes. Direct and water
      mediated hydrogen bonding interactions stabilize these binding modes and play an
      essential role in defining the order of specificity for different
      monosialogangliosides towards cholera toxin. This study identifies the NeuNAc
      binding site as a site for design of inhibitors that can restrict the pathogenic
      activity of cholera toxin.

PMID- 14692803
TI  - Bronchial epithelial-myoepithelial carcinoma.
AB  - Epithelial-myoepithelial tumor is extremely rare as a pulmonary neoplasm. Only 20
      cases have been reported to date, of which 14 were malignant. We report a case of
      intrabronchial epithelial-myoepithelial carcinoma in a 73-year-old man with a
      history of heavy smoking. The tumor was well-circumscribed and caused distal
      airway obstruction. Histologically, the tumor showed glandular and solid
      architecture. The glands were composed of an inner layer of epithelial cells and
      an outer layer of myoepithelial cells. The solid areas consisted of spindle
      shaped myoepithelial cells. Immunohistochemical staining was positive for p53 and
      c-Kit (CD117). Focal atypia and increased mitotic activity were present, but no
      vascular invasion or nodal metastasis was identified.

PMID- 14692804
TI  - Eosinophilic angiocentric fibrosis: an unusual entity of the sinonasal tract.
AB  - We present the case of a 45-year-old man who presented with medication-resistant
      chronic bilateral nasal obstruction. The patient had no known history of allergy
      or any other disease. Nasal septoplasty was performed to relieve his symptoms.
      Histologically, thick collagen bundles were seen, characteristically whorling
      around vessels in a fibrotic stroma. Inflammatory cells, rich in eosinophils,
      were scattered throughout the lesion. No granulomas, necrosis, or vessel
      destruction were present. A diagnosis of eosinophilic angiocentric fibrosis was
      made. This neoplasm, which has very characteristic histologic features, is a rare
      entity of the sinonasal tract.

PMID- 14692805
TI  - Spindle cell transformation of papillary carcinoma: an aggressive entity distinct
      from anaplastic thyroid carcinoma.
AB  - Spindle cells are not routinely encountered in the context of thyroid pathology
      and are most often present in anaplastic thyroid carcinoma, medullary thyroid
      carcinoma, and benign conditions such as Riedel struma or de Quervain
      granulomatous thyroiditis. Only a few publications have reported papillary
      thyroid carcinoma admixed with a prominent spindle cell component. While these
      tumors are clearly distinct from anaplastic thyroid carcinoma, prognostication as
      to their oncologic potential is not yet established. We describe a unique case of
      spindle cell transformation of papillary thyroid carcinoma. The blandness of the
      spindle cells was so impressive as to dissuade us from a malignant diagnosis on
      preoperative biopsies. However, this patient unfortunately died shortly after
      transformation of this papillary thyroid carcinoma. We conclude that this
      peculiar and rare spindle cell transformation should be regarded as a potentially
      lethal variant of papillary thyroid carcinoma.

PMID- 14692807
TI  - Pathology informatics questions and answers from the University of Pittsburgh
      pathology residency informatics rotation.
AB  - CONTEXT: Effective pathology practice increasingly requires familiarity with
      concepts in medical informatics that may cover a broad range of topics, for
      example, traditional clinical information systems, desktop and Internet computer
      applications, and effective protocols for computer security. To address this
      need, the University of Pittsburgh (Pittsburgh, Pa) includes a full-time, 3-week
      rotation in pathology informatics as a required component of pathology residency
      training. OBJECTIVE: To teach pathology residents general informatics concepts
      important in pathology practice. DESIGN: We assess the efficacy of the rotation
      in communicating these concepts using a short-answer examination administered at
      the end of the rotation. Because the increasing use of computers and the Internet
      in education and general communications prior to residency training has the
      potential to communicate key concepts that might not need additional coverage in
      the rotation, we have also evaluated incoming residents' informatics knowledge
      using a similar pretest. DATA SOURCES: This article lists 128 questions that
      cover a range of topics in pathology informatics at a level appropriate for
      residency training. These questions were used for pretests and posttests in the
      pathology informatics rotation in the Pathology Residency Program at the
      University of Pittsburgh for the years 2000 through 2002. With slight
      modification, the questions are organized here into 15 topic categories within
      pathology informatics. The answers provided are brief and are meant to orient the
      reader to the question and suggest the level of detail appropriate in an answer
      from a pathology resident. RESULTS: A previously published evaluation of the test
      results revealed that pretest scores did not increase during the 3-year
      evaluation period, and self-assessed computer skill level correlated with pretest
      scores, but all pretest scores were low. Posttest scores increased substantially,
      and posttest scores did not correlate with the self-assessed computer skill level
      recorded at pretest time. CONCLUSIONS: Even residents who rated themselves high
      in computer skills lacked many concepts important in pathology informatics, and
      posttest scores showed that residents with both high and low self-assessed skill
      levels learned pathology informatics concepts effectively.

PMID- 14692806
TI  - Extramammary Paget disease of the scrotum with features of Bowen disease.
AB  - The scrotum is an uncommon site for the presentation of extramammary Paget
      disease (EMPD). We describe a case of EMPD that was discovered in a patient who
      had been previously diagnosed and treated for squamous cell carcinoma in situ of
      the scrotum 3 years earlier. Pathologic examination of the current scrotectomy
      specimen revealed an erythematous patch with areas of pale induration.
      Microscopic examination revealed areas with the characteristic histology of Paget
      disease adjacent to areas characteristic of Bowen disease. Immunohistochemical
      findings demonstrated a strong expression of carcinoembryonic antigen,
      cytokeratin 7, and low-molecular-weight cytokeratins (CAM 5.2) in both of these
      areas, giving support to the overall diagnosis of EMPD. High-molecular-weight
      cytokeratins (34betaE12) were uncharacteristically expressed in the cytoplasm of
      the Paget cells with equal or greater strength than in the surrounding
      keratinocytes, suggesting some degree of squamous differentiation. Very few
      publications have reported the coexistence of EMPD with squamous cell carcinoma
      in situ, occurring mostly in the vulva. To our knowledge, our case is the first
      report of scrotal EMPD with features of Bowen disease. Our findings support the
      theory that primary EMPD arises multifocally from multipotential epidermal cells.

PMID- 14692808
TI  - Transforming growth factor alpha and epidermal growth factor receptor in reactive
      and malignant mesothelial proliferations.
AB  - BACKGROUND: Growth factors such as transforming growth factor alpha (TGF-alpha)
      and epidermal growth factor receptor (EGFR) play an important role in cell
      proliferation. The immunohistochemical expression of these factors has been
      extensively studied in malignant tumors including mesothelioma. However, the
      comparative expression of these growth factors in mesothelioma and reactive
      mesothelial proliferations has been less well studied. OBJECTIVE: To evaluate the
      possible role of TGF-alpha and EGFR in the clinically important distinction
      between reactive mesothelial proliferations and malignant mesothelioma. METHODS:
      The expression of TGF-alpha and EGFR was studied in 39 cases of mesothelioma and
      30 cases of reactive mesothelial proliferations by means of immunohistochemistry.
      RESULTS: Fourteen (70%) of 20 reactive mesothelial proliferations tested and 29
      (76%) of 38 mesotheliomas tested expressed TGF-alpha. One (3%) of 30 reactive
      mesothelial proliferations and 17 (45%) of 39 mesotheliomas expressed EGFR.
      CONCLUSIONS: These results suggest an up-regulation of EGFR in mesothelioma as
      compared with reactive mesothelial proliferations. This up-regulation further
      suggests a possible use of EGFR as an adjunct immunohistochemical test in the
      differential diagnosis of mesothelioma and reactive mesothelial proliferations.

PMID- 14692809
TI  - Total fibrous obliteration of main portal vein and portal foam cell venopathy in
      chronic hepatic allograft rejection.
AB  - CONTEXT: Chronic hepatic allograft rejection is characterized by arteriopathy and
      bile duct loss. Pathology of the portal vein or its branches is not considered to
      play a major role in chronic rejection. OBJECTIVE: A recent case of chronic
      rejection with total fibrous obliteration of the portal vein at the hilum and
      graft loss prompted us to retrospectively analyze cases of failed allografts for
      portal vein changes. DESIGN: Six cases of failed hepatic allograft recorded in
      our files from 1994 to 1998 were selected for the study. For comparison, 4 cases
      of hepatitis C cirrhosis were included. Clinical features, including arteriograms
      or Doppler studies, were reviewed whenever available. Sections taken from the
      hilum and random parenchyma stained with routine hematoxylin-eosin, elastic van
      Gieson, and Masson trichrome were examined by 3 experienced liver pathologists in
      a randomized, blinded fashion. RESULTS: Significant hepatic artery occlusion with
      foam cell change and bile duct loss was seen in all cases of chronic rejection
      (3/3), but not in the other cases. Foam cell change in the portal vein at the
      hilum (3/3) and occasionally into the distal branches (2/3) with variable
      occlusion of the lumen was seen only in cases of chronic hepatic allograft
      rejection. Mild luminal narrowing was observed in all the cases of cirrhosis
      (4/4) as a result of phlebosclerosis, most likely representing a change secondary
      to portal hypertension. Total obliteration of the portal vein at the hilum was
      seen in the index case (case 1) only. CONCLUSION: Portal venopathy can be a
      significant finding in chronic hepatic allograft rejection and may contribute to
      graft dysfunction or failure. Two-vessel disease must be considered in cases of
      chronic hepatic allograft rejection, and pathologists should thoroughly examine
      the hilum in explanted hepatic allografts.

PMID- 14692810
TI  - Management training for pathology residents: a regional approach.
AB  - CONTEXT: Success in the practice of pathology demands proficiency in management,
      but management training for pathology residents is generally inadequate, with
      little agreement on an appropriate curriculum or competency assessment. Most
      residency training programs do not have faculty members who are interested and
      have expertise in management and who are dedicated to and have time available for
      teaching. OBJECTIVE: To develop a didactic management training program for the
      residents from 6 separate pathology residency programs in Southern California,
      with a comprehensive curriculum taught by experts in each area without undue
      burden on any single training program. METHODS: Faculty from the University of
      California-Los Angeles and the University of Southern California reviewed the
      literature and the management needs of practicing pathologists and devised the
      curriculum. Pathologist and nonpathologist speakers were identified who were
      working in important management positions both regionally and nationally.
      Seminars were presented in alternate months during a 2-year period. Sessions were
      videotaped, and each session was evaluated by the attendees. RESULTS: The
      curriculum consisted of 12 major topics, and seminars were delivered by 15
      presenters from 6 institutions. Attendance was highest for residents in
      postgraduate years 2 and 3. The overall evaluation scores were exceedingly high
      (4.66 of a possible 5.0), and residents reported a significant increase in
      subject knowledge. Videotaping of presentations provided flexibility for
      residents who were unable to attend the seminars. CONCLUSION: This program was
      effective and could serve as a template for other pathology residency training
      programs to establish curriculum content and develop resident competency.
      Teaching responsibilities were less burdensome when spread among several programs
      and when supplemented by nonpathology faculty. Electronic and audiovisual support
      enhanced flexibility and access to the program.

PMID- 14692811
TI  - Macrofollicular variant of papillary carcinoma of the thyroid: a histologic,
      cytologic, and immunohistochemical study of 3 cases and review of the literature.
AB  - CONTEXT: The macrofollicular variant of papillary carcinoma of the thyroid is a
      rare entity described by J. Albores-Saavedra and colleagues in 1991. It is
      characterized histologically by a predominance of macrofollicles and clinically
      by a low incidence of metastasis. This entity may represent a source of
      diagnostic error, since it can be easily misinterpreted as a macrofollicular
      adenoma or nodular goiter. DESIGN: In this study, we describe 3 cases of
      papillary carcinoma of the thyroid with a macrofollicular growth pattern and
      review the literature. RESULTS: The fine-needle aspiration biopsies in 2 cases
      showed large cells with optically clear nuclei and nuclear grooves, suggestive of
      papillary carcinoma of the thyroid. In one case, the cytology showed no signs of
      malignancy. In all cases, the tumors showed a combination of the conventional
      follicular variant of papillary carcinoma of the thyroid and macrofollicles
      (diameter, >250 microm) occupying more than 50% of the cross-sectional area.
      Cytologic features were large, cuboidal cells with optically clear, ground-glass
      nuclei with smooth outlines, a fine chromatin pattern, nuclear grooves, and
      pseudoinclusions. The colloid was dense and more eosinophilic than in adjacent
      normal follicles. In 2 cases, there was capsular or blood vessel infiltration,
      and one tumor had metastasized to a cervical lymph node. One tumor recurred 1
      year later as an anaplastic carcinoma. Immunohistochemical staining showed a
      positivity of the tumor cells for cytokeratins 7, 17, and 19, thyroid
      transcription factor-1, and galectin-3 and a negativity for cytokeratin 20 and
      p53. CONCLUSIONS: Although it has been suggested that this tumor is a highly
      differentiated variant with a favorable prognosis, our study shows that its
      biologic behavior is not conclusive because metastases and recurrences with
      dedifferentiation may occur.

PMID- 14692812
TI  - Early nodular hyperplasia of the liver occurring with inflammatory bowel diseases
      in association with thioguanine therapy.
AB  - CONTEXT: Nodular hyperplasia (also referred to as nodular regenerative
      hyperplasia and nodular regenerative hyperplasia of the liver) is a sequel to
      therapy with thioguanine in patients with hematologic malignancies. Recently, 6
      thioguanine has been used to treat patients with inflammatory bowel disease who
      have been resistant to other forms of therapy. OBJECTIVE: To study liver biopsies
      from 3 patients with inflammatory bowel disease who had received thioguanine for
      more than a year, and who had elevated serum liver enzyme values and underwent
      percutaneous liver biopsy. DESIGN: Percutaneous liver biopsies and histologic
      examinations were performed, including staining with the reticulin silver
      impregnation method. RESULTS: All 3 patients had foci of nodular regenerative
      hyperplasia, which was best seen with the reticulin silver impregnation method.
      CONCLUSIONS: Thioguanine-treated inflammatory bowel disease patients are at risk
      for the development of nodular hyperplasia. Reticulin-stained histologic sections
      are necessary to recognize this change. Further studies are needed to determine
      the frequency and significance of this change.

PMID- 14692813
TI  - Evaluation of linearity in the clinical laboratory.
AB  - CONTEXT: Clinical laboratory assessment of test linearity is often limited to
      satisfying regulatory requirements rather than integrating this tool into the
      laboratory quality assurance program. Although an important part of quality
      control and method validation for clinical laboratories, linearity of clinical
      tests does not get the attention it deserves. OBJECTIVE: This article evaluates
      the concepts and importance of linearity evaluations for clinical tests. DESIGN:
      We describe the theory and procedural steps of each linearity evaluation. We then
      evaluate the statistical methods for each procedure. RESULTS: Visual assessment,
      although simple, is subjective. The lack-of-fit error and the 1986 NCCLS EP6-P G
      test are sensitive to imprecision and assume that the data are first order.
      Regression analysis, as developed as the polynomial method, is partly based on
      the experiences of the College of American Pathologists Instrumentation Resource
      Committee and has proved to be a robust statistical method. CONCLUSIONS: We
      provide general guidelines for handling non-linear results from a linearity
      evaluation. Handling linearity data in an objective manner will aid clinical
      laboratorians whose goal is to improve the quality of the tests they perform.

PMID- 14692814
TI  - Survivin and Bcl-2 expression in prostatic adenocarcinomas.
AB  - CONTEXT: Dysregulated cell proliferation caused by inhibitors of programmed cell
      death (apoptosis) contributes to tumor progression and spread. Aberrant
      expression of Bcl-2, the most notable inhibitor of apoptosis, has been well
      characterized in several human malignancies. Recent studies have described a
      novel apoptosis inhibitor, survivin, in human carcinomas, although its exact role
      remains to be characterized. OBJECTIVE: The purpose of this study was to evaluate
      the immunohistochemical expression of Bcl-2 and survivin proteins in prostate
      cancer and to correlate the results with clinicopathologic variables. DESIGN:
      Formalin-fixed, paraffin-embedded tissue sections from 138 cases of prostatic
      adenocarcinomas (PACs) were immunostained by an automated method using specific
      antibodies against survivin and Bcl-2. Staining was semiquantitatively scored
      based on both intensity and distribution, and results were correlated with
      morphologic and prognostic variables. RESULTS: Of the 138 PACs tested, 113 (82%)
      expressed survivin. We found no correlation between survivin expression and
      prognostic variables, including grade, stage, DNA content (ploidy), and
      recurrence. Bcl-2 expression was positive in 95 (69%) of these 138 cases and
      correlated with nondiploid DNA content. Fourteen (50%) of 28 nondiploid PACs
      expressed Bcl-2, compared to 17 (25%) of 68 diploid tumors (P =.02). A trend for
      association of Bcl-2 expression with tumor stage was noted as follows: 21 (39%)
      of 54 advanced-stage PACs expressed Bcl-2, in comparison with 20 (24%) of 84 low
      stage tumors (P =.07). On univariate analysis, 25 (48%) of the 52 PACs that
      recurred expressed Bcl-2, as compared with 16 (19%) of the 86 nonrecurrent PACs
      (P <.001). No correlation was noted between survivin and Bcl-2 expression.
      CONCLUSION: Survivin is expressed in a majority of PACs and is not a prognosis
      related marker, but may be a potential target for apoptosis-based therapy.
      Overexpression of Bcl-2 correlates with other prognostic variables and predicts
      disease recurrence of PACs. These data also suggest that survivin and Bcl-2 may
      regulate cell proliferation and cell death through different mechanisms.

PMID- 14692815
TI  - Comorbidity in dementia: an autopsy study.
AB  - CONTEXT: There is a paucity of accurate postmortem data pertinent to comorbid
      medical conditions in patients with dementia, including Alzheimer disease.
      OBJECTIVES: The purposes of this study were (a) to examine general autopsy
      findings in patients with a dementia syndrome and (b) to establish patterns of
      central nervous system comorbidity in these patients. DESIGN: Review of autopsy
      reports and selected case material from 202 demented patients who had "brain
      only" autopsies during a 17-year period (1984-2000) and from 52 demented patients
      who had general autopsies during a 6-year period (1995-2000). SETTING: Large
      academic medical center performing approximately 200 autopsies per year. RESULTS:
      Among the 52 patients who underwent complete autopsy, the most common cause of
      death was bronchopneumonia, which was found in 24 cases (46.1%). Other
      respiratory problems included emphysema, found in 19 (36.5%) of 52 patients, and
      pulmonary thromboembolism, found in 9 (17.3%) of 52 patients. In 6 cases,
      pulmonary thromboembolism was the proximate cause of death. Twenty-one (40.3%) of
      the 52 patients had evidence of a myocardial infarct (varying ages) and 38
      (73.1%) had atherosclerotic cardiovascular disease, 27 of a moderate to severe
      degree. Four clinically unsuspected malignancies were found: 1 each of
      glioblastoma multiforme, diffusely infiltrative central nervous system lymphoma,
      pancreatic adenocarcinoma, and adenocarcinoma of the lung. One patient with
      frontotemporal dementia and amyotrophic lateral sclerosis died of severe
      meningoencephalitis/ventriculitis, probably secondary to seeding of the central
      nervous system by an infected cardiac valve. Of the 202 demented patients who
      underwent brain-only autopsies, the following types of dementia were found: 129
      (63.8%) cases showed changes of severe Alzheimer disease, 21 (10.4%) showed
      combined neuropathologic abnormalities (Alzheimer disease plus another type of
      lesion, such as significant ischemic infarcts or diffuse Lewy body disease), 12
      (5.9%) cases of relatively pure ischemic vascular dementia, 13 (6.4%) cases of
      diffuse Lewy body disease, and 8 (4.0%) cases of frontotemporal dementia. The
      remaining 19 (9.4%) patients showed miscellaneous neuropathologic diagnoses,
      including normal pressure hydrocephalus and progressive supranuclear palsy. Among
      the demented patients, 92 (45.5%) had cerebral atherosclerosis, which was
      moderate to severe in 65 patients (32.2%). CONCLUSIONS: Some of the conditions
      found at autopsy, had they been known antemortem, would likely have affected
      clinical management of the patients. Autopsy findings may be used as a quality-of
      care measure in patients who have been hospitalized in chronic care facilities
      for a neurodegenerative disorder.

PMID- 14692816
TI  - Current applications of flow cytometry in the diagnosis of primary
      immunodeficiency diseases.
AB  - CONTEXT: To review the applications of flow cytometry in the diagnosis and
      management of primary immunodeficiency disease. DATA SOURCES: Articles describing
      the use of flow cytometry in the diagnosis of several primary immunodeficiency
      diseases were obtained through the National Library of Medicine database. STUDY
      SELECTION: Publications that described novel and known applications of flow
      cytometry in primary immunodeficiency disease were selected. Review articles were
      included. Articles describing the different immunodeficiency diseases and methods
      of diagnosis were also selected. DATA EXTRACTION: Approximately 100 data sources
      were analyzed, and those with the most relevant information were selected. DATA
      SYNTHESIS: The diagnosis of many primary immunodeficiency diseases requires the
      use of several laboratory tests. Flow cytometry has become an important part of
      the workup of individuals suspected to have such a disorder. Knowledge of the
      pathogenesis of many of these diseases continues to increase, hence we acquire a
      better understanding of the laboratory tests that may be helpful in diagnosis.
      CONCLUSIONS: Flow cytometry is applicable in the initial workup and subsequent
      management of several primary immunodeficiency diseases. As our understanding of
      the pathogenesis and management of these diseases increases, the use of many of
      these assays may become routine in hospitals.

PMID- 14692817
TI  - Comparison of performance of conventional and ThinPrep gynecologic preparations
      in the College of American Pathologists Gynecologic Cytology Program.
AB  - CONTEXT: Results of clinical trials suggest that interpretation of liquid-based
      cytology preparations is more accurate and is associated with less screening
      error than interpretation of conventional preparations. OBJECTIVE: In this study,
      the performance of participants in interpreting ThinPrep (TP) preparations was
      compared with participants' performance on conventional Papanicolaou tests in the
      College of American Pathologists Interlaboratory Comparison Program in
      Cervicovaginal Cytology (PAP). DESIGN: The results of the PAP from the year 2002
      were reviewed, and the discordancies to series and exact-match error rates for
      the 2 cytologic methods were compared. RESULTS: For this study, a total of 89 815
      interpretations from conventional smears and 20 886 interpretations from TP
      samples were analyzed. Overall, interpretations of TP preparations had both
      significantly fewer false-positive (1.6%) and false-negative (1.3%) rates than
      those of conventional smears (P =.001 and P =.02, respectively) for validated or
      validated-equivalent slides, as assessed by concordance with the correct
      diagnostic series. In this assessment of concordance to series, interpretations
      of educational TP and conventional preparations were similar, except for high
      grade squamous intraepithelial lesion, in which the performance was significantly
      worse for educational TP preparations (false-negative rate of 8.1% vs 4.1% for
      conventional smears, P <.001). When interpretations were matched to the exact
      diagnosis, validated-equivalent TP preparations were generally more accurate for
      diagnoses in the 100 series and 200 series than were conventional smears.
      Notably, for the reference diagnosis of squamous cell carcinoma, the exact-match
      error rate on validated equivalent TP slides was significantly greater than that
      of conventional slides (44.5% vs 23.1%, P <.001). Interpretations of educational
      TP preparations also had a significantly higher error rate in matching to the
      exact reference diagnosis for squamous cell carcinoma (33.7% vs 22.8%, P =.007).
      CONCLUSIONS: Overall, TP preparations in this program were associated with
      significantly lower error rates than conventional smears for both validated and
      educational cases. However, unlike the negative for intraepithelial lesion and
      malignancy, not otherwise specified, low-grade squamous intraepithelial lesion,
      and adenocarcinoma cytodiagnostic challenges, participants' responses indicated
      some difficulty in recognizing high-grade squamous intraepithelial lesion and
      squamous cell carcinoma.

PMID- 14692820
TI  - The challenge of using autopsy information for quality improvement.

PMID- 14692822
TI  - Pancreatic heterotopia in the gastric antrum.

PMID- 14692823
TI  - Delivering human papillomavirus testing to the public.

PMID- 14692824
TI  - Pathologic quiz case: an 82-year-old woman with a renal mass. Renal cell
      carcinoma with rhabdoid features.

PMID- 14692825
TI  - Pathologic quiz case: a 53-year-old man with chest pain and cough. Malignant
      (diffuse) pleural mesothelioma, biphasic variant, with heterologous
      differentiation.

PMID- 14692826
TI  - Pathologic quiz case: patient with testicular pain. Benign Leydig cell tumor.

PMID- 14692827
TI  - Pathologic quiz case: a 27-week female fetus with massive macrocephaly and
      generalized anasarca. Congenital immature intracranial teratoma with skull
      rupture and high output cardiac failure.

PMID- 14692829
TI  - Carcinosarcoma of the urinary bladder following cyclophosphamide therapy:
      evidence for monoclonal origin and chromosome 9p allelic loss.
AB  - We report a case involving a 45-year-old man with a 12-year history of Wegener
      granulomatosis, who developed a carcinosarcoma of the urinary bladder after long
      term cyclophosphamide therapy. Cyclophosphamide is well recognized as an
      etiologic agent for urothelial carcinoma of the urinary bladder. However, only 5
      cases of carcinosarcoma of the urinary bladder following cyclophosphamide therapy
      have been reported. We used loss of heterozygosity studies and microsatellite
      markers to define the molecular basis of this rare neoplasm. These studies
      revealed evidence supporting a monoclonal origin for the 2 components of this
      tumor. We also demonstrated allelic loss of chromosome 9p. This loss associated
      with carcinosarcoma of the urinary bladder is in agreement with previous studies,
      suggesting a possible role for the tumor suppressor gene p16 in the pathogenesis
      of this tumor.

PMID- 14692828
TI  - Characterization of human melanoma cell lines according to their migratory
      properties in vitro.
AB  - The migratory responses of four human melanoma cell lines (A-2058, DEMEL, HTB-63,
      and HTB-72), using chemotaxis (CTX) and haptotaxis (HPTX) assays, were studied.
      The attractants were three extracellular matrix components (EMCs), fibronectin,
      laminin, and collagen type IV. The conditioned media (CM) of each cell line were
      used to study autocrine and paracrine responses. A screening and sensitive CTX
      assay was performed, using pertussis toxin (PTX)- treated A-2058 as responder
      cells; the other melanoma cells and normal cells were used as secretory cells.
      Autotaxin (ATX), a purified autocrine motility factor, was also used as a
      chemoattractant. Reverse transcriptase-polymerase chain reaction was used to
      detect the expression of ATX by all cell lines. The secretion of ATX was
      determined by Western blot. The invasive capacity of the cell lines was evaluated
      using Matrigel and ATX as attractant. Chemotaxis responses to EMCs varied. Except
      for the A-2058 cells, HPTX migration was low. Autocrine and paracrine responses
      also varied. The migration of PTX-treated A-2058 cells to ATX and to their own CM
      was abolished. All the melanoma cells expressed ATX, and except for the HTB-72
      and normal cells, all secreted ATX. Matrigel was invaded by all the melanoma cell
      lines except the HTB-72 and normal cells. The migratory properties of human
      melanoma cells in vitro suggest that they could correlate to their metastatic
      potential in vivo.

PMID- 14692830
TI  - Intraocular inflammatory myofibroblastic tumor with ALK overexpression.
AB  - We report a case of an intraocular inflammatory myofibroblastic tumor nearly
      filling the vitreous cavity of the eye of a 50-year-old man. The tumor was
      composed of a mixture of spindle cells and mixed inflammatory elements, including
      numerous plasma cells. The differential diagnosis included inflammatory
      pseudotumor and neoplastic mimics of this condition. Further investigation with
      immunohistochemistry revealed the mass to be composed of myofibroblasts, positive
      for smooth muscle actin stains and with weak anaplastic lymphoma kinase (ALK)
      expression in some tumor cells. Evaluation by fluorescence in situ hybridization
      revealed the tumor cells to have multiple copies of chromosome 2 and ALK but no
      rearrangement of the ALK gene. The authors propose that multiple copies of the
      ALK gene may be involved in inflammatory myofibroblastic tumor tumorigenesis, in
      addition to ALK gene rearrangements.

PMID- 14692831
TI  - Pathologic quiz case: a 63-year-old woman with a pigmented perineal lesion.
      Extramammary Paget disease.

PMID- 14692832
TI  - Pathologic quiz case: a large recurrent thigh mass in a 79-year-old woman.
      Inflammatory liposarcoma occurring as a component of a recurrent, well
      differentiated, lipoma-like liposarcoma.

PMID- 14692833
TI  - Solitary fibrous tumor of nasal cavity in patient with long-standing history of
      cocaine inhalation.
AB  - We report a solitary fibrous tumor in the nasal cavity of a 48-year-old woman who
      presented with a history of bilateral nasal obstruction and long-standing cocaine
      inhalation. Physical examination revealed a large mass involving the right nasal
      cavity and extending into the posterior aspect of the left nasal cavity. The
      computed tomography scan showed opacification of airways. During surgery, the
      mass was found to involve the entire nasal cavity, with extension to the right
      maxillary sinus, posterior nasal airways, and left nasal cavity. The mass was
      completely excised. Pathologic examination revealed a polypoid mass 3.7 x 3.0 x
      1.2 cm. This tumor was composed of spindle cells that were cytologically bland in
      a background of ropey and nodular collagen, giving a "patternless" pattern.
      Immunohistochemically, the neoplastic cells stained for CD34 and vimentin but not
      for S100 protein, keratin, desmin, HMB-45, and c-Kit. This immunohistochemical
      pattern confirmed the diagnosis of solitary fibrous tumor. Although solitary
      fibrous tumors are usually found in the pleura, they can occur in various other
      locations, such as the orbit, nasal cavity, paranasal sinuses, mediastinum,
      breast, vagina, meninges, and soft tissues. This case is of interest because the
      tumor occurred in a patient with prolonged cocaine inhalation. Such an
      association has not been previously described. The exact causal relationship
      between cocaine inhalation and the tumor is not known.

PMID- 14692834
TI  - Pathologic quiz case: renal mass in an otherwise healthy man. Epithelioid
      angiomyolipoma.

PMID- 14692835
TI  - Pathologic quiz case: a 30-year-old man with a white plaque in the oral mucosa.
      Smokeless tobacco keratosis.

PMID- 14692836
TI  - Pathologic quiz case: multiple cutaneous lesions in a 27-year-old woman.
      Cutaneous Histoplasmosis capsulatum.

PMID- 14692837
TI  - Pathologic quiz case: a 17-year-old renal transplant patient with persistent
      fever, pancytopenia, and axillary lymphadenopathy. Bacillary angiomatosis of the
      lymph node in the renal transplant recipient.

PMID- 14692838
TI  - A unique collision tumor in breast: invasive ductal carcinoma and mucosa
      associated lymphoid tissue lymphoma.
AB  - We report an extraordinary case of a collision tumor consisting of invasive
      ductal carcinoma with adjacent malignant lymphoma presenting as a single mass in
      the breast. A 79-year-old woman presented with a breast mass. A core biopsy
      performed at an outside hospital was interpreted as medullary carcinoma. On
      review of the breast core biopsy, a diagnosis of a synchronous malignant lymphoma
      and invasive ductal carcinoma was rendered. The patient underwent lumpectomy and
      axillary dissection. The excised specimen revealed a 2.1-cm, moderately
      differentiated invasive ductal carcinoma, partially surrounded by malignant
      lymphoma with areas where both tumors were intermixed. All 27 axillary lymph
      nodes were extensively involved by lymphoma, and 1 lymph node demonstrated
      metastatic carcinoma. The morphology and results of immunohistochemistry, flow
      cytometry, and cytogenetic analysis were consistent with extranodal marginal zone
      B-cell lymphoma of mucosa-associated lymphoid tissue.

PMID- 14692839
TI  - Small intestinal angiosarcoma leading to perforation and acute abdomen: a case
      report and review of the literature.
AB  - A 76-year-old man presented to the emergency room with abdominal pain and
      fatigue. The patient had a history of gastrointestinal bleeding. An abdominal
      computed tomographic scan showed collections of free air in the abdomen with
      obstruction of the distal small intestine and multiple masses in the liver.
      Laparotomy revealed a widespread malignant neoplasm in the abdomen, with multiple
      tumor nodules in the ileal wall, mesentery, and liver. The ileal wall was
      perforated within the area of one of the tumors. Pathologic examination of the
      lesion showed a neoplasm composed of solid sheets of spindle and undifferentiated
      cells, forming interlacing delicate vascular channels with atypical endothelial
      cells. The tumor cells were positive for the endothelial marker CD31, whereas
      reactivity for a broad panel of epithelial and other endothelial markers was
      negative. This case demonstrates that although angiosarcomas of the
      gastrointestinal tract are rare, they should be considered in cases of intestinal
      perforation or severe bleeding, especially in the elderly. A broad panel of
      immunochemical markers might be necessary to establish the pathologic diagnosis.

PMID- 14692840
TI  - Introduction to the special section on incremental validity and utility in
      clinical assessment.
AB  - This special section focuses on the incremental validity and utility of clinical
      assessment data. The lack of replicated incremental validity research limits the
      ability of psychologists to establish their assessment practices on a solid
      empirical footing. The articles in this section deal with conceptual,
      methodological, and content issues in the development and use of clinical
      measures. The authors addressed several aspects of incremental validity research,
      including (a) the evaluation of the magnitude of validity increments, (b) the use
      of incremental validity data for test development and validation, (c) the costs
      of assessment, (d) the use of multi-informant and multimethod assessments, and
      (e) the treatment utility of assessment. Obstacles limiting the use of
      incremental validity research to inform and guide clinical practice are also
      emphasized.

PMID- 14692841
TI  - The incremental validity of psychological testing and assessment: conceptual,
      methodological, and statistical issues.
AB  - There has been insufficient effort in most areas of applied psychology to
      evaluate incremental validity. To further this kind of validity research, the
      authors examined applicable research designs, including those to assess the
      incremental validity of test instruments, of test-informed clinical inferences,
      and of newly developed measures. The authors also considered key statistical and
      measurement issues that can influence incremental validity findings, including
      the entry order of predictor variables, how to interpret the size of a validity
      increment, and possible artifactual effects in the criteria selected for
      incremental validity research. The authors concluded by suggesting steps for
      building a cumulative research base concerning incremental validity and by
      describing challenges associated with applying nomothetic research findings to
      individual clinical cases.

PMID- 14692842
TI  - Incremental validity of new clinical assessment measures.
AB  - The authors address conceptual and methodological foundations of incremental
      validity in the evaluation of newly developed clinical assessment measures.
      Incremental validity is defined as the degree to which a measure explains or
      predicts a phenomenon of interest, relative to other measures. Incremental
      validity can be evaluated on several dimensions, such as sensitivity to change,
      diagnostic efficacy, content validity, treatment design and outcome, and
      convergent validity. Indices of incremental validity can vary depending on the
      criterion measures, comparison measures, and individual differences in samples.
      The authors review the rationale for, principles, and methods of incremental
      validation, including the selection of comparison and criterion measures, and
      address data analytic strategies and the conditional nature of incremental
      validity evaluations in the selection of measures. Incremental validity
      contributes to, but is different from, cost-benefits, which reflect the cost of
      acquiring the data and the benefits from the data. The impact of an incremental
      validity index on whether a measure is selected will be moderated by the cost of
      acquiring the new data, the importance of the measured phenomenon, and the
      clinical utility of the new data.

PMID- 14692843
TI  - Incremental validity principles in test construction.
AB  - The authors articulate 5 basic principles for enhancing incremental validity,
      both among elements within a test and between tests, during test construction:
      (a) careful, precise articulation of each element or facet within the content
      domain; (b) reliable measurement of each facet through use of multiple, alternate
      form items; (c) examination of incremental validity at the facet level rather
      than the broad construct level; (d) use of items that represent single facets
      rather than combinations of facets; and (e) empirical examination of whether
      there is a broad construct or a combination of separate constructs. Using these
      principles, the authors offer specific suggestions for modifications in 3 classic
      test construction approaches; (a) criterion keying, (b) inductive test
      construction, and (c) deductive test construction. Implementation of these
      suggestions is likely to provide theoretical clarification and improved
      prediction.

PMID- 14692844
TI  - Assessing the costs, benefits, cost-effectiveness, and cost-benefit of
      psychological assessment: we should, we can, and here's how.
AB  - To the extent that assessment improves the effectiveness of treatment,
      prevention, or other services, it can be said to be effective. If an assessment
      is as effective as alternatives for improving treatment and less costly, it can
      be said to be cost-effective. If that improvement in the effectiveness of the
      service is monetary or monetizable, the assessment can be judged beneficial. And,
      if the sum of monetary and monetizable benefits of assessment exceeds the sum of
      the costs of treatment, the assessment can be said to be cost-beneficial. An
      overview of cost-related issues is followed by practical strategies that
      researchers and administrators can use to measure incremental costs, incremental
      effectiveness, and incremental benefits of adding psychological assessments to
      other psychological interventions.

PMID- 14692845
TI  - Incremental validity in the psychological assessment of children and adolescents.
AB  - Incremental validity in the process of psychological assessment of children and
      adolescents is explored. The authors highlight the dependence of the incremental
      validity of assessment information on factors such as goal of assessment, other
      information available, base rate of the problem or outcome, age or gender of the
      child, and type of problem being assessed. The authors discuss the incremental
      validity of assessment information from alternate sources, methods, and
      constructs. In view of the limited number of studies directly relevant to
      incremental validity in child clinical assessments, the authors call for more
      clinically relevant research. To have the greatest impact on child and adolescent
      services, this research must be readily generalized and immediately relevant to
      actual clinical practice.

PMID- 14692846
TI  - Incremental validity and the assessment of psychopathology in adults.
AB  - Results from studies on incremental validity are described for (a) interviews,
      (b) personality inventories, (c) projective techniques, and (d) brief self-rated
      and clinician-rated measures. In some of the studies (clinical judgment studies),
      psychologists were given increasing amounts of information. In other studies
      (statistical prediction studies), increasing amounts of assessment information
      were entered into a statistical prediction rule. Although relatively little
      research has been conducted on incremental validity, results that have been
      obtained tend to favor the use of interviews, personality inventories (e.g., the
      Minnesota Multiphasic Personality Inventory--2; J. N. Butcher, W. G. Dahlstrom,
      J. R., Graham, A. Tellegen, & B. Kaemmer, 1989), and brief self-rated measures
      (e.g., the Anxiety Sensitivity Index, S. Reiss, R. A. Peterson, D. M. Gursky, &
      R. M. McNally, 1986). Results are generally less encouraging for projective
      techniques.

PMID- 14692847
TI  - Treatment utility of psychological assessment.
AB  - This article focuses on treatment utility. A definition of treatment utility was
      provided by S. C. Hayes, R. O. Nelson, and R. B. Jarrett (1987): "We propose to
      use the phrase the treatment utility of assessment to refer to the degree to
      which assessment is shown to contribute to beneficial treatment outcome" (p.
      963). Various methodologies to examine the treatment utility of assessment are
      summarized. Treatment utility studies using various assessment procedures (i.e.,
      diagnosis and functional analysis) and various disorders (i.e., unipolar
      depression, social or interpersonal problems, and phobic disorders) are
      described. Suggestions are made as to when elaborated assessment and/or treatment
      utility studies are needed. Limitations on the generalizability of results of any
      particular treatment utility study are presented. Despite progress, for most
      assessment procedures and devices, the treatment utility question remains; What
      is the degree to which assessment is shown to contribute to beneficial treatment
      outcome?

PMID- 14692848
TI  - Measuring adjustment to chronic skin disorders: validation of a self-report
      measure.
AB  - This article describes the development of a questionnaire that assesses problems
      in adapting to chronic skin disorders, the Adjustment to Chronic Skin Diseases
      Questionnaire. Patients (N = 442) with different skin disorders completed the
      original item pool. Principal-components analysis suggested a 6-factor solution
      that was largely replicated with 2 additional samples of 192 patients with
      psoriasis or atopic dermatitis and 165 patients with atopic dermatitis. Four of
      the subscales showed very good internal consistencies, retest reliabilities, and
      sufficient correlations with expert ratings: Social Anxiety/Avoidance, Itch
      Scratch Cycle, Helplessness, and Anxious-Depressive Mood. Two short additional
      subscales, Impact on Quality of Life and Deficit in Active Coping, showed
      moderate internal consistencies, but good retest reliabilities. Correlations of
      the subscales with measures of depression, anxiety, and coping, and meaningful
      differences between dermatological subgroups support their construct validity. A
      treatment study showed that changes in some of the subscales correlated with
      changes in the severity of the skin condition.

PMID- 14692849
TI  - Is it prudent to administer all items for each Child Behavior Checklist cross
      informant syndrome? Evaluating the psychometric properties of the Youth Self
      Report dimensions with confirmatory factor analysis and item response theory.
AB  - Through surveying of children in 10 nations with parent, teacher, and Youth Self
      Report (YSR) forms of the Child Behavior Checklist (CBCL), cross-informant
      syndromes (CISs) were derived and cross-validated by sample-dependent
      methodology. Generalizing CBCL syndromes and norms to nations excluded from its
      normative sample is problematic. This study used confirmatory factor analyses
      (CFAs) to test factor model fit for CISs on the YSR responses of 625 Jamaican
      children ages 11 to 18 years. Item response theory (IRT), a sample-independent
      methodology, was used to estimate the psychometric properties of individual items
      on each dimension. CFAs indicated poor to moderate model-to-data fit. Across all
      syndromes, IRT analyses revealed that more than 3/4 of the cross-informant items
      yielded little information. Eliminating such items could be cost effective in
      terms of administration time yet improve the measures discrimination across
      syndrome severity levels.

PMID- 14692850
TI  - Psychometric properties of the Spanish Beck Depression Inventory-II in a medical
      sample.
AB  - The authors examined the psychometric properties of the Spanish Beck Depression
      Inventory-II (BDI-II; A. T. Beck, R. A. Steer, & G. K. Brown, 1996) in a sample
      of individuals undergoing hemodialysis. They performed a confirmatory factor
      analysis of a previously reported 2-factor solution for the English BDI-II
      derived from a medical sample. Results indicate that the established model for
      the English-speaking medical sample provided adequate fit in the present sample.
      Spanish BDI-II scores were not significantly associated with age or gender in
      their sample, but they were significantly associated with disease severity.
      Bilingual participants completed the inventory in both Spanish and English, and
      their data revealed that BDI-II total scores were similar across language
      administration. The preliminary data suggest that the Spanish BDI-II can be
      reliably used in medical samples.

PMID- 14692851
TI  - The Children's Yale-Brown Obsessive-Compulsive Scale: item structure in an
      outpatient setting.
AB  - The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) is one of the most
      popular measures of symptom severity for childhood obsessive-compulsive disorder
      (OCD). This study describes the factor structure of the CY-BOCS. A total of 233
      children diagnosed with OCD were evaluated with the CY-BOCS. The results
      indicated that 2 alternate 2-factor solutions (obsessions and compulsions;
      severity and disturbance) fit the data set best. The results also suggested that
      items assessing resistance to obsessions and compulsions provide unreliable
      evaluations of these symptoms in children with OCD. Recommendations for
      modifications to the CY-BOCS as well as clinical applications and for future
      research with the measure are made.

PMID- 14692852
TI  - Let's call the whole thing off: a response to Dawes (2001).
AB  - There has been a recent controversy regarding the validity of the Rorschach test.
      This comment is in response to criticism levied by R. M. Dawes (2001) on the
      incremental validity of the Ego Impairment Index (EII), a Rorschach-derived
      measure of cognition, perception, and reasoning. The Dawes articles (1999 and
      2001) serve as an example of the recent practice of placing extraordinary
      challenges on the Rorschach test. Dawes's arguments are examined and parallel
      examples are provided that demonstrate the bias used to judge the validity of the
      EII, the Rorschach, and psychological assessment. Still, in the face of
      criticism, the results (see Dawes, 2001) support the incremental validity of the
      EII. Thus, the conclusion presented in this Comment is that it is time for us to
      "call the whole thing off" and end the Rorschach controversy that has occupied so
      much recent attention and generated so few new ideas.

PMID- 14692853
TI  - Introduction to the Special Section on Applied Longitudinal Methods in Aging
      Research.
AB  - This article introduces articles that appear in the special section on applied
      longitudinal methods in aging research. These articles apply quantitative
      statistical techniques such as multilevel modeling and structural equation models
      to the analysis of longitudinal data. They exemplify how applications of these
      techniques can advance scientific research on the effects of aging on
      psychological constructs. ((c) 2003 APA, all rights reserved)

PMID- 14692854
TI  - Assessing psychological change in adulthood: an overview of methodological
      issues.
AB  - This article reviews the current status of methods available for the analysis of
      psychological change in adulthood and aging. Enormous progress has been made in
      designing statistical models that can capture key aspects of intraindividual
      change, as reflected in techniques such as latent growth curve models and
      multilevel (random-effects) models. However, the rapid evolution of statistical
      innovations may have obscured the critical importance of addressing rival
      explanations for statistical outcomes, such as cohort differences or practice
      effects that could influence estimates of age-related change. Choice of modeling
      technique and implementation of a specific modeling approach should be grounded
      in and reflect both the theoretical nature of the developmental phenomenon and
      the features of the sampling design that selected persons, variables, and
      contexts for empirical observation.

PMID- 14692855
TI  - Modeling memory decline in older adults: the importance of preclinical dementia,
      attrition, and chronological age.
AB  - This longitudinal study examined memory loss in a sample of 391 initially
      nondemented older adults. Analyses decomposed observed memory loss into decline
      associated with preclinical dementia, study attrition, terminal decline, and
      chronological age. Measuring memory as a function of only chronological age
      failed to provide an adequate representation of cognitive change. Disease
      progression accounted for virtually all of the memory loss in the 25% of the
      sample that developed diagnosable dementia. In the remainder of the sample, both
      chronological age and study attrition contributed to observed memory loss. These
      results suggest that much of memory loss in aging adults may be attributable to
      the progression of preclinical dementia and other nonnormative aging processes
      that are not captured by chronological age.

PMID- 14692856
TI  - Correlated and coupled cognitive change in older adults with and without
      preclinical dementia.
AB  - Common factor aging theories state that correlations among cognitive age effects
      signify a single underlying causal process. The logic underlying this proposition
      was evaluated by examining correlated cognitive change in a sample of 391
      initially nondemented older adults who were tested annually for up to 16 years.
      Between-person correlations among rates of change (range = .56-.61) were partly
      attributable to model misspecification and the aggregation of heterogeneous
      groups of individuals. Correlated within-person cognitive change was much
      stronger in the cases (.45-.51) than in the noncases (.07-.18). These results
      demonstrate that correlated change may either signify causal commonality or the
      cumulative effects of multiple age-related conditions that can affect multiple
      cognitive systems.

PMID- 14692857
TI  - Changes in functional status among older adults in Japan: successful and usual
      aging.
AB  - This research aimed to chart the trajectories of functional status in old age in
      Japan and to assess how self-rated health and cognitive functioning differentiate
      these trajectories and account for interpersonal differences. Data came from a 5
      wave panel study of a national sample of 2,200 Japanese older adults between 1987
      and 1999. The sample as a whole showed an accelerated increase in functional
      limitations with age. approximated by a quadratic function. More important, 3
      major trajectories of functional change were identified: (a) minimal functional
      decrement, (b) early onset of functional impairment. and (c) late onset of
      functional impairment. These findings may serve as useful benchmarks for
      observations derived from other developed nations.

PMID- 14692858
TI  - Age-based structural dynamics between perceptual speed and knowledge in the
      Berlin Aging Study: direct evidence for ability dedifferentiation in old age.
AB  - According to 2-component theories of intelligence, negative cross-sectional age
      gradients in mechanic (broad Gf) and pragmatic (broad Gc) cognitive components
      reflect the increasing constraining of the former in the expression and integrity
      of the latter component. The authors examined this widely held but untested
      assumption by applying a recently proposed dynamic structural modeling technique,
      the bivariate dual change score model, to longitudinal data from the Berlin Aging
      Study (N = 516, age range = 70-103 years). Mechanics and pragmatics were indexed
      by perceptual speed and knowledge, respectively. As hypothesized, results
      indicated that changes in knowledge are dominated by perceptual speed and offered
      strong support for the notion of "mechanization" of pragmatic abilities in old
      and very old age.

PMID- 14692859
TI  - A latent growth curve analysis of late-life sensory and cognitive function over 8
      years: evidence for specific and common factors underlying change.
AB  - Correlations among rates of change in sensory and cognitive functioning in
      adulthood were evaluated. Measures of Vision, Hearing, Memory, Speed and Verbal
      ability were obtained in 1992, 1994, and 2000 in the Australian Longitudinal
      Study of Aging (N = 2,087 at baseline). Data from 1,823 participants who
      undertook at least 1 clinical assessment were analyzed using latent growth curve
      models. A significant moderate-sized association between rates of change in
      Memory and Vision was found. This remained after statistically controlling for
      the effects of age, gender, education, self-rated health, medical conditions, and
      depressive symptoms. Rate of change in Hearing was weakly associated with rate of
      change in Memory. The results support a theory incorporating a major role for
      unique factors in addition to common factors underlying sensory and cognitive
      change in old age.

PMID- 14692860
TI  - Adult age differences in multiple cognitive functions: differentiation,
      dedifferentiation, or process-specific change?
AB  - Adult age differences in covariance structures of latent variables of vocabulary,
      list recall, speed, working memory, and text recall, were analyzed to test
      hypotheses of structural changes with age. There were baseline data from 613 men
      and women aged 30-97, data from a second wave of testing from 322 people, and
      complete longitudinal data from 289 people. There were age differences in the
      size but not configuration of factor loadings cross-sectionally but not
      longitudinally. There were no changes in factor standard deviations or
      covariances. Findings did not support models of dedifferentiation with age.

PMID- 14692861
TI  - The relative importance of three domains of positive and negative social
      exchanges: a longitudinal model with comparable measures.
AB  - Researchers have expressed considerable interest in the question of whether
      positive or negative social exchanges more strongly affect psychological health,
      but previous studies have been limited by using nonparallel measures of positive
      and negative social exchanges, by measuring negative affect only, and by relying
      largely on cross-sectional designs. The independent effects of positive and
      negative exchanges on both positive and negative affect were examined in a short
      term longitudinal study of 277 older adults, using social exchange measures with
      parallel content and equivalent reliability and validity. In cross-sectional
      analyses, positive exchanges predicted positive affect, and negative exchanges
      predicted negative affect. In longitudinal analyses, however, negative exchanges
      predicted both positive and negative affect, whereas positive exchanges were
      unrelated to either outcome. The more potent and longer-lasting effects of
      negative exchanges have important implications for theory and interventions.

PMID- 14692862
TI  - Latent change models of adult cognition: are changes in processing speed and
      working memory associated with changes in episodic memory?
AB  - The authors used 6-year longitudinal data from the Victoria Longitudinal Study
      (VLS) to investigate individual differences in amount of episodic memory change.
      Latent change models revealed reliable individual differences in cognitive
      change. Changes in episodic memory were significantly correlated with changes in
      other cognitive variables, including speed and working memory. A structural
      equation model for the latent change scores showed that changes in speed and
      working memory predicted changes in episodic memory, as expected by processing
      resource theory. However, these effects were best modeled as being mediated by
      changes in induction and fact retrieval. Dissociations were detected between
      cross-sectional ability correlations and longitudinal changes. Shuffling the
      tasks used to define the Working Memory latent variable altered patterns of
      change correlations.

PMID- 14692863
TI  - Predicting individual change in support over time among chronically impaired
      older adults.
AB  - Hierarchical linear modeling was used to examine the degree of individual change
      in friendship and family networks and support over time as a function of
      sociodemographic characteristics, rehabilitation use, and disability.
      Participants, 449 older adults, had age-related vision loss, a common, chronic
      impairment that tends to worsen over time. Three interviews were conducted
      (baseline and 6- and 18-month follow-ups). All network and support variables
      showed a decrease over time. Regarding factors predicting individual variation,
      age (younger) and education (lower) were associated with greater baseline
      friendship support, rehabilitation was related to maintaining a larger friend
      network, and disability was positively associated with family network and
      support. Results supported the importance of examining rates of individual change
      and factors associated with variability in multiple support components by
      relationship type.

PMID- 14692864
TI  - Aging and repetition effects: separate specific and nonspecific influences.
AB  - The research reported in this article focuses on processes that contribute to the
      repetition effect in 2-alternative forced-choice tasks and on how these processes
      change with age. An analytical approach is presented that allows researchers to
      discriminate between 2 components of performance. The results of Experiment 1
      show that differences in the relative contributions of these 2 processes can
      produce differences in repetition effects between younger and older adults.
      Furthermore, as in the negative priming domain, increasing the contribution of 1
      of these 2 components can eliminate this age difference. Together, the results
      argue against the practice of attributing age differences in repetition effects
      to deficits in any single cognitive process.

PMID- 14692865
TI  - The effects of age and dementia of the Alzheimer's type on phonological false
      memories.
AB  - The authors conducted 3 experiments that examined the effects of age and dementia
      of the Alzheimer's type (DAT) on phonological false memories. In addition, the
      study was designed to investigate the role of inhibitory control in mediating
      phonological false memories. In Experiment 1, both young-old and old-old
      participants exhibited increased susceptibility to false remembering, compared
      with young adults. In Experiment 2, auditory Stroop interference was used as an
      index of inhibitory abilities and was found to account for a significant
      percentage of the variance in false recollection. Experiment 3 provided
      converging evidence for the importance of inhibitory control in phonological
      false memories by demonstrating that DAT patients are more susceptible to false
      recall and recognition than healthy older adults. The results are discussed
      within the inhibitory deficit framework of cognitive aging.

PMID- 14692866
TI  - Age differences in implicit memory: conceptual, perceptual, or methodological?
AB  - The authors examined age differences in conceptual and perceptual implicit memory
      via word-fragment completion, word-stem completion, category exemplar generation,
      picture-fragment identification, and picture naming. Young, middle-aged, and
      older participants (N = 60) named pictures and words at study. Limited test
      exposure minimized explicit memory contamination, yielding no reliable age
      differences and equivalent cross-format effects. In contrast, explicit memory and
      neuropsychological measures produced significant age differences. In a follow-up
      experiment, 24 young adults were informed a priori about implicit testing. Their
      priming was equivalent to the main experiment, showing that test trial time
      restrictions limit explicit memory strategies. The authors concluded that most
      implicit memory processes remain stable across adulthood and suggest that
      explicit contamination be rigorously monitored in aging studies.

PMID- 14692867
TI  - Aging and maintaining intentions over delays: do it or lose it.
AB  - When execution of retrieved intentions must be briefly delayed, older adults
      display deficits in performing those intentions (G. O. Einstein, M. A. McDaniel,
      M. Manzi, B. Cochran, & M. Baker, 2000). This initial finding was extended by
      showing age-related deficits with 5-s unfilled delays, with instructions to
      rehearse during the delay, and with divided attention during initial retrieval of
      the intention. Performance increased with a break at the end of the delay period,
      such that when combined with full attention (during retrieval), older adults'
      performance approached that of younger adults. These results suggest that age
      compromises maintenance of information in awareness. Consequently, when forced to
      delay execution of retrieved intentions, older adults may rely more on plan
      reformulation and subsequent retrieval of the intention from long-term memory at
      the end of the delay.

PMID- 14692868
TI  - WAIS-R factor structure in Alzheimer's disease patients: a comparison of
      alternative models and an assessment of their generalizability.
AB  - The WAIS-R is often used in neuropsychological evaluations of individuals with
      probable Alzheimer's disease (AD), but its factor structure in this population is
      unknown. Moreover, theories and past research findings make competing predictions
      concerning its structure. Using confirmatory factor analysis, the authors
      compared 5 alternative WAIS-R factor models among 516 AD patients: 1-factor
      (Spearman's g) and 2-factor (Verbal IQ and Performance IQ) models; a 3-factor
      model including Verbal Comprehension (VC), Perceptual Organization (PO), and
      Freedom From Distractibility (FD) factors; a 3-factor model in which Digit Symbol
      loads on PO rather than FD; and a 3-factor model in which Digit Symbol loads on
      both PO and FD. Results favored the 3-factor model in which Digit Symbol loads on
      PO rather than FD. Moreover, this model fit the data best among subsamples of
      patients defined by age, dementia severity, years of education, and gender.

PMID- 14692869
TI  - Effects of pain on functioning and well-being in older adults with osteoarthritis
      of the knee.
AB  - The effects of pain on functioning and well-being were examined in 367 older
      adults with osteoarthritis (OA) of the knee. The relationship of OA-related pain
      to depressive symptoms and perceived health was hypothesized to be direct as well
      as mediated by physical and social functioning. Results showed that OA-related
      pain was related to poorer physical and social functioning, had a direct effect
      on depressive symptoms, and direct and indirect effects on perceived health.
      Lower social functioning was related to more depressive symptoms, and both lower
      social and physical functioning predicted worse perceived health. Thus,
      distinguishing between physical and social functioning when examining the costs
      of OA-related pain is useful. Moreover, existing pain-psychological well-being
      models can be generalized to perceived health.

PMID- 14692870
TI  - Enmeshed lives: adult children with developmental disabilities and their aging
      mothers.
AB  - This article uses equity theory to examine the ways in which aging mothers and
      their adult children with developmental disabilities support each other and the
      effects that this exchange has on the caregiving satisfaction and burden of the
      mothers. Data from 305 mothers revealed that exchange flows both from mother to
      child and from child to mother. Results indicate that caregiving satisfaction
      increased when affection from child to mother was greater. Caregiving burden was
      not affected by either functional support or affection from child to mother.

PMID- 14692871
TI  - Sounds, words, sentences: age-related changes across levels of language
      processing.
AB  - Age-related changes in sensory, lexical, and sentence processing were examined
      and compared using event-related potentials (ERPs) recorded as young and elderly
      participants listened to natural speech for comprehension. Lexically associated
      and unassociated word pairs were embedded in meaningful or syntactically legal
      but meaningless sentences. Early, general sensory, and attention-related
      responses (N1, P2) were delayed by about 25 ms for older participants, but later
      components indexing semantic processing (N400) were not delayed. There were no
      differences in the size, timing, or distribution of lexical associative effects
      for the two groups. In contrast, message-level context effects were delayed by
      more than 200 ms in the elderly group. The results support models that posit age
      related changes primarily in higher order language processes.

PMID- 14692872
TI  - The effects of aging and divided attention on memory for item and associative
      information.
AB  - The present study examined how aging and divided attention influence memory for
      item and associative information. Older adults and younger adults working under
      full-attention conditions and younger adults working under divided-attention
      conditions studied unrelated word pairs. Memory for item information was measured
      by later recognition of the 2nd word in the pair, and associative information was
      measured by recognition of the entire pair. Both older adults in the full
      attention condition and younger adults in the divided-attention condition
      performed more poorly than younger adults in the full-attention condition, with
      the deficit in associative information being greater than the deficit in item
      information. In addition, a differentially greater associative decrement was
      found for the older adults, as shown by their heightened tendency to make false
      alarm responses to re-paired (conjunction) distractors. The results are discussed
      in terms of an age-related reduction in processing resources compounded by an age
      related increase in older adults' reliance on familiarity in associative
      recognition memory.

PMID- 14692873
TI  - The Revised Memory and Behavior Problems Checklist--Nursing Home: instrument
      development and measurement of burden among certified nursing assistants.
AB  - Confirmatory factor analysis of the Revised Memory and Behavior Problems
      Checklist--Nursing Home (RMBPC) replicated the factor structure of the community
      based RMBPC (L. Teri et al., 1992). The reliability of the total score was high
      as indexed by estimates of internal consistency (alpha = .95), test-retest
      reliability (r = .86), and interrater reliability between 2 interviewers (r =
      .88). Notably, the interrater reliability between 2 independent certified nursing
      assistants (CNAs) regarding residents' behavior problem frequency was more modest
      (r = .46), possibly reflecting the degree to which resident behaviors capture
      individual CNA's attention. This may have implications for the interpretation of
      data from the Minimum Data Set. CNAs reported moderately severe burden associated
      with behavior problems in 47% of residents under their care.

PMID- 14692874
TI  - Coping with deficits and losses in later life: from compensatory action to
      accommodation.
AB  - Processes of coping with performance deficits in different domains of functioning
      were investigated in a 4-year longitudinal study involving a core sample of 762
      participants (initial age range: 58-81 years). Compensatory efforts to counteract
      functional impairments were found to increase up to the age of 70 years. Above
      that age, a decrease in compensatory efforts was observed that was linked to a
      decrease in the availability and efficiency of action resources. Contentment with
      actual performance levels remained stable across the entire age range of the
      study. Stability of self-evaluations was found to depend on adjustment of
      personal standards: Scarce action resources were accompanied by a lowering of
      personal comparison standards and by a downgrading of the importance of the
      respective domains. Accepting more lenient standards of comparison was found to
      buffer negative effects of performance deficits on contentment with performance
      among the older participants.

PMID- 14692876
TI  - Religiousness, spirituality, and psychosocial functioning in late adulthood:
      findings from a longitudinal study.
AB  - This study used longitudinal data to examine the relations among religiousness,
      spirituality, and 3 key domains of psychosocial functioning in late adulthood:
      (a) sources of well-being, (b) involvement in tasks of everyday life, and (c)
      generativity and wisdom. Religiousness and spirituality were operationalized as
      distinct but overlapping dimensions of individual difference. In late adulthood,
      religiousness was positively related to well-being from positive relations with
      others, involvement in social and community life tasks, and generativity.
      Spirituality was positively related to well-being from personal growth,
      involvement in creative and knowledge-building life tasks, and wisdom. Neither
      religiousness nor spirituality was associated with narcissism. The relations
      between religiousness, spirituality, and outcomes in late adulthood were also
      observed using religiousness scored in early and spirituality scored in late
      middle adulthood. All analyses were controlled for gender, cohort, social class,
      and the overlap between religiousness and spirituality.

PMID- 14692875
TI  - Psychometric analysis of the Revised Memory and Behavior Problems Checklist:
      factor structure of occurrence and reaction ratings.
AB  - A modified version of the Revised Memory and Behavior Problems Checklist (RMBPC;
      L. Teri et al., 1992) was administered across 6 different sites to 1,229 family
      caregivers of community-dwelling adults with dementia. The total sample was
      divided randomly into 2 subsamples. Principal components analyses on occurrence
      responses and reaction ratings from the first subsample resulted in a 3-factor
      solution that closely resembled the originally proposed dimensions (memory
      related problems, disruptive behaviors, and depression). Confirmatory factor
      analyses on data from the second subsample indicated adequate fit for the 3
      factor model. Correlations with other caregiver and care-recipient measures
      supported the convergent and discriminant validity of the RMBPC measures. In
      addition, female caregivers and White caregivers reported more problems, on
      average, than male caregivers and African American caregivers, respectively.

PMID- 14692877
TI  - A new ephrin-A1 isoform (ephrin-A1b) with altered receptor binding properties
      abrogates the cleavage of ephrin-A1a.
AB  - Ephrins are ligands for the Eph receptor tyrosine kinases, which play important
      roles in patterning nervous and vascular systems. Ephrin-A1 is a
      glycosylphosphatidylinositol-anchored ligand that binds to the EphA receptor
      tyrosine kinases. In the present study, we have identified a new ephrin-A1
      isoform, denoted ephrin-A1b (ephrin-A1 isoform b). Compared with the originally
      described ephrin-A1 sequence, ephrin-A1a [Holzman, Marks and Dixit (1990) Mol.
      Cell. Biol. 10, 5830-5838], ephrin-A1b lacks a segment of 22 amino acids
      (residues 131-152). At the transcript level, exon 3 is spliced out in the
      transcript encoding ephrin-A1b. Transfection of HEK-293T cells (human embryonic
      kidney 293 cells) with an ephrin-A1b-expressing plasmid resulted in a significant
      expression of the protein on the cell surface. However, soluble EphA2 receptor
      (EphA2-Fc) bound weakly to ephrin-A1b-expressing transfectants, but bound
      strongly to ephrin-A1a-expressing transfectants. Ephrins have been shown to
      undergo regulated cleavage after interaction with their receptors. This process
      is inhibited by co-expression of ephrin-A1a and ephrin-A1b, indicating that
      ephrin-A1b influences the cleavage process. Taken together, these findings
      indicate that this newly described isoform may regulate the function of its
      ephrin-A1a counterpart.

PMID- 14692881
TI  - The sensitivity of 18-fluorodopa positron emission tomography and magnetic
      resonance imaging in Parkinson's disease.
AB  - Parkinson's disease (PD) as the most important movement disorder is characterized
      by a progressive loss of nigral dopamine neurons and a subsequent degeneration
      within several other transmitter systems. Functional brain imaging with positron
      emission tomography (PET) and the radiotracer 18-fluorodopa (FDOPA) is capable to
      quantify the deficiency of dopamine synthesis and storage within pre-synaptic
      striatal nerve terminals. Therefore, FDOPA-PET allows the diagnosis of PD in
      early disease stages and the differentiation of clinically unclear cases from
      other movement disorders, e.g. essential tremor. Additionally, FDOPA-PET imaging
      permits the follow-up of disease progression, the assessment of medical and
      surgical PD therapy strategies with possible neuroprotective properties and the
      detection of pre-clinical disease in subjects at risk for the disorder. The
      classical domain of morphological magnetic resonance imaging (MRI) is the
      differentiation of symptomatic Parkinsonism from PD. However, recent advances in
      MRI data acquisition and analysis techniques demonstrated MRI to be also a
      valuable tool for detection of nigral pathology in PD and for differentiation of
      neurodegenerative disorders with atypical Parkinsonism.

PMID- 14692878
TI  - Beta-glucosidase, exo-beta-glucanase and pyridoxine transglucosylase activities
      of rice BGlu1.
AB  - The bglu1 cDNA for a beta-glucosidase cloned from rice (Oryza sativa L.)
      seedlings was expressed as a soluble and active protein in Escherichia coli and
      designated BGlu1. This enzyme hydrolysed beta-1,4-linked oligosaccharides with
      increasing catalytic efficiency (kcat/Km) values as the DP (degree of
      polymerization) increased from 2 to 6. In contrast, hydrolysis of beta-1,3-linked
      oligosaccharides decreased from DP 2 to 3, and polymers with a DP greater than 3
      were not hydrolysed. The enzyme also hydrolysed p -nitrophenyl beta-D-glycosides
      and some natural glucosides but with lower catalytic efficiency than beta-linked
      oligosaccharides. Pyridoxine 5'-O-beta-D-glucoside was the most efficiently
      hydrolysed natural glycoside tested. BGlu1 also had high transglucosylation
      activity towards pyridoxine, producing pyridoxine 5'-O-beta-D-glucopyranoside in
      the presence of the glucose donor p-nitrophenyl beta-D-glucoside.

PMID- 14692882
TI  - Serum IgM anti-GM1 ganglioside antibodies in lower motor neuron syndromes.
AB  - Lower motor neuron syndromes (LMNS) are heterogenous conditions, which include
      patients with progressive lower motor neuron disease (LMND) and cases with the
      clinical phenotype of motor neuropathy (MN). The aim of this study was to
      estimate the IgM anti-GM1 ganglioside antibodies titer and the ratio of the light
      chains in order to define the presence of autoimmunity process in particular
      cases with LMNS. Twenty-eight patients were diagnosed with LMND and 15 patients
      were diagnosed with MN (10 patients with multifocal motor neuropathy with
      conduction block, five patients with MN without conduction block). Total of 103
      patients with classical amyotrophic lateral sclerosis (ALS) and 50 healthy, age
      matched persons were also tested. The IgM anti-GM1 ganglioside titer and the
      ratio of lambda/kappa light chains in serum were determined using the ELISA
      technique. High titer of IgM anti-GM1 antibodies were detected in serum of 46%
      LMND patients, 80% of MN patients, and 18% of the classical ALS cases. An
      elevated ratio of lambda/kappa light chains appeared in 18% of LMND patients, and
      in 67% of the MN cases. The lambda/kappa light chains ratio was normal in all ALS
      patients. The presence of elevated titer of IgM anti-GM1 ganglioside antibodies
      and the changed ratio of the light chains supports the presence of autoimmune
      process in LMNS and may provide clues for their management.

PMID- 14692883
TI  - Differences in cerebrospinal fluid dynamics do not affect the levels of
      biochemical markers in ventricular CSF from patients with aqueductal stenosis and
      idiopathic normal pressure hydrocephalus.
AB  - To compare levels of biochemical markers in ventricular cerebrospinal fluid
      (vCSF) between patients with aqueductal stenosis (AS) and idiopathic normal
      pressure hydrocephalus (INPH) and relate these results to clinical outcome after
      surgery. Neurofilament light protein, tau protein, sulfatide, vasoactive
      intestinal peptide (VIP), neuropeptide PYY (NPY) and CSF/serum albumin ratio were
      measured in vCSF from 18 consecutive AS and 19 consecutive INPH patients.
      Clinical outcome was evaluated after surgery by standardized indices. The levels
      of markers were related to clinical outcome. No differences in any of the markers
      were found between AS and INPH patients. The concentration of sulfatide and
      albumin ratio correlated inversely with psychometric improvement, whilst VIP and
      NPY correlated inversely with improvement in alertness. The similar levels of
      biochemical markers in vCSF from AS and INPH patients indicate similarities in
      pathophysiology and turnover rate of vCSF despite differences in CSF dynamics.
      High albumin ratio and sulfatide concentrations in vCSF in hydrocephalus patients
      have negative implications for surgical outcome and might indicate concomitant
      cerebrovascular disorder.

PMID- 14692884
TI  - Etiology of and risk factors for cerebral infarction in young adults in western
      Norway: a population-based case-control study.
AB  - We sought to study the etiology of and risk factors for cerebral infarction in
      young adults in Hordaland County, Norway. All patients aged 15-49 years living in
      Hordaland County with a first-ever cerebral infarction during 1988-97 were
      included. Etiology was analyzed in subgroups defined by sex, age (<40 years
      versus >/=40 years), circulation territory (anterior versus posterior
      circulation) and short-term functional outcome [modified Rankin score (mRS) </= 2
      versus mRS > 2]. A questionnaire was used to evaluate possible risk factors
      amongst the patients compared with an age- and sex-matched control group. The
      distribution of etiology was significantly different in all subgroups.
      Atherosclerosis was frequent amongst men (22.8% vs. 4.2%) and patients >/= 40
      years (20.8% vs. 2.7%). All patients with microangiopathy had favorable short
      term outcome. Significant risk factors were smoking more than 15 cigarettes per
      day (P < 0.001), hypertension (P = 0.001), and myocardial infarction (P = 0.035).
      Modifiable risk factors were frequent.

PMID- 14692885
TI  - Horizontal canal benign paroxysmal positioning vertigo with ipsilateral hearing
      loss.
AB  - The etiology of benign paroxysmal positioning vertigo (h-BPPV) of the horizontal
      semicircular is unknown. Insight was obtained from two patients with h-BPPV and
      associated hearing impairment. Based on the different inner ear lesion patterns
      in neurolabyrinthitis contrary to ischemic labyrinthine infarction we assessed
      multiple vestibulo-cochlear functions for the first time in two patients who
      suffered from h-BPPV with sudden unilateral hearing loss. While in patient no. 1
      the lesion pattern (posterior canal paresis in addition to the sudden hearing
      loss) could possibly be caused by ischemia of the common cochlear artery, the
      lesion pattern of patient no. 2 (hearing loss and ipsilateral paresis of the
      posterior and horizontal semicircular canal) exceeds the typical vascular
      labyrinthine territories and may indicate viral neurolabyrinthitis.

PMID- 14692886
TI  - Investigation of cytokine (tumor necrosis factor-alpha, interleukin-6,
      interleukin-10) concentrations in the cerebrospinal fluid of female patients with
      multiple sclerosis and systemic lupus erythematosus.
AB  - Humoral immune response seems to play a role in the pathogenesis of multiple
      sclerosis (MS) and in the central nervous system (CNS) complications of systemic
      lupus erythematosus (SLE). The aim of the present study was to compare the levels
      of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-10 in the
      cerebrospinal fluid of female patients with several forms of MS (50 patients),
      and in female patients with several types of CNS complications in SLE (50
      patients). Samples were investigated using an enzyme-linked immunosorbent assay
      technique. Involvement of CNS in SLE patients seems to be characterized with
      elevated concentrations of all three cytokines in CNS and intrathecal synthesis
      of IL-6. In MS patients, an intrathecal synthesis of TNF-alpha (relapsing
      remitting form) and IL-6 (primary progressive form) were observed. Clinical forms
      of MS seem to be immunologically heterogeneous. The activation of cytokine
      network was observed in SLE patients with CNS complications, independent of the
      pathological process. Similarities between SLE and MS patients with the primary
      progressive form of the disease were demonstrated concerning the intrathecal
      synthesis of IL-6. Only MS patients with the relapsing-remitting clinical form
      showed intrathecal TNF-alpha synthesis.

PMID- 14692887
TI  - Treatment optimization in multiple sclerosis: report of an international
      consensus meeting.
AB  - Multiple sclerosis (MS) is a chronic disease for which there is currently no
      proven cure. Nevertheless, desperate views have changed to substantial optimism
      over recent years, as several lines of evidence have indicated that disease
      modifying drugs (DMDs) have beneficial effects on neurological deterioration in
      MS. However, assessing the success of DMD therapy in an individual patient may
      not always be clear-cut for the doctor. In order to address this issue, an
      International Working Group of doctors experienced in treating patients with MS
      convened to discuss the optimization of DMD therapy, and the outcome of this
      consensus meeting is reported here. Participants developed statements that
      classify changes in relapses, disease progression and brain magnetic resonance
      imaging in a patient with MS who is taking DMD therapy, according to whether they
      are worthy of note, of some concern, or of serious concern and requiring a
      reassessment of current therapy. Based on these statements, the performance of
      standardized examinations to document changes in the disease enables a visual
      measure of the progress of an individual patient to be built up on an analogue
      model. This model provides a useful framework to help the neurologist to identify
      those patients for whom the therapeutic options should be reconsidered.

PMID- 14692888
TI  - Pneumonia and urinary tract infection after acute ischaemic stroke: a tertiary
      analysis of the GAIN International trial.
AB  - The third most common stroke complication is infection. We studied the rates of
      aspiration pneumonia and urinary tract infection (UTI), their risk factors and
      their effect on outcome in the 1455 Glycine Antagonist (Gavestinel) in
      Neuroprotection (GAIN) International patients with ischaemic stroke. Forward
      stepwise logistic regression and Cox proportional hazards modelling identified
      baseline factors that predicted events and the independent effect of events up to
      day 7 on poor stroke outcome at 3 months in patients alive at day 7, after
      correcting for prognostic factors. Higher baseline National Institute of Health
      Stroke Scale (NIHSS) and age, male gender, history of diabetes and stroke subtype
      predicted pneumonia, which occurred in 13.6% of patients. Female gender and
      higher baseline NIHSS and age predicted UTI, which occurred in 17.2% of patients.
      Pneumonia was associated with poor outcome by mortality (hazard ratio, 2.2; 95%
      confidence interval, 1.5-3.3), Barthel index (<60) (odds ratio, 3.8; 2.2-6.7),
      NIHSS (4.9; 1.7-14) and Rankin scale (>/=2) (3.4; 1.4-8.3). UTI was associated
      with Barthel index (1.9; 1.2-2.9), NIHSS (2.2; 1.2-4.0) and Rankin scale (3.1;
      1.6-4.9). Pneumonia and UTI are independently associated with stroke poor
      outcome. Patients with identified risk factors must be closely monitored for
      infection.

PMID- 14692889
TI  - Unusual form of neurocysticercosis associated with HIV infection.
AB  - Concurrent infection with Taenia solium and HIV would be expected to occur more
      frequently because of the increasing frequency of HIV infection in endemic areas
      of cysticercosis. However, little is known about the influence of HIV infection
      on the frequency and the clinical course of cysticercosis. Giant cysts and
      racemose forms of neurocysticercosis seem to be more frequent in HIV-infected
      patients and may be secondary to an uncontrolled parasitic growth because of an
      impaired cell-mediated immune response. We report an unusual case of epidural
      spinal racemose neurocysticercosis revealed by compression of cauda equina in an
      HIV-infected man and discuss the potential interactions between T. solium and HIV
      infections.

PMID- 14692890
TI  - Rapidly reversible dementia in cerebral amyloid inflammatory vasculopathy.
AB  - This report discusses a biopsy proven case of cerebral amyloid angiopathy, with
      additional prominent vascular inflammatory features, characterized by a rapidly
      progressive dementia and leukoencephalopathy, where the clinical and radiological
      abnormalities resolved rapidly with minimal therapeutic intervention. We propose
      the term cerebral amyloid inflammatory vasculopathy (CAIV) to describe this
      condition.

PMID- 14692891
TI  - Early CT changes and outcome of ischemic stroke.
AB  - Although recombinant tissue plasminogen activator (rt-PA) was rapidly implemented
      as part of the emergency care of acute stroke, its use in daily clinical practice
      still remains controversial in many countries. The most important question is
      criteria for careful selection of subgroup of patients for this treatment. It has
      been hypothesized that early computed tomography (CT) changes of ischemia are
      risk factors for symptomatic intracerebral hemorrhage and poor outcome. We
      conducted a prospective outcome study of patients with acute ischemic stroke (IS)
      admitted to the hospital within 6 h of symptom onset. Experienced
      neuroradiologists blind to the clinical outcome of the patients read all CT scans
      carried out in the emergency room. Early CT changes were defined as in European
      Cooperative Acute Stroke Study (ECASS) 2. There were 150 patients (75 males, mean
      age 72.5 +/- 9.0) with acute IS (54.7% with mild stroke and 45.3% with severe
      stroke). Early CT changes were presented with tissue hypodensity - 55.7%,
      effacement of sulci - 41.3%, hyperdensity of middle cerebral artery (MCA) -
      13.3%, hypodensity of lentiform - 20.7%, loss of insular ribbon sign - 28.7%.
      Follow-up after 30 days showed that 44% of the patients were discharged home, 20%
      were discharged to rehabilitation facilities, 22% were discharged to chronic care
      institutions and 14% died. Data were statistically analyzed. Our data suggest
      that early signs on CT scan could not predict outcome of patients with acute IS.

PMID- 14692892
TI  - Isolated ischemic internuclear ophthalmoplegia: toward the resolution limits of
      DW-MRI.

PMID- 14692893
TI  - Neurotoxicity of acyclovir and valacyclovir in a hemodialyzed patient.

PMID- 14692900
TI  - Epilepsy guidelines in the real world: the sound of music?

PMID- 14692894
TI  - Bilateral spontaneous dissection of the internal carotid arteries.

PMID- 14692901
TI  - Transplants of cells engineered to produce GABA suppress spontaneous seizures.
AB  - PURPOSE: Cell transplantation into the brain is an aggressive clinical
      alternative. The hopes of treating diseases like intractable temporal lobe
      epilepsy have been subdued because the preclinical successes thus far have shown
      only slowing of epileptogenesis, or suppression of electrically induced seizures.
      Because the hallmark of epilepsy is spontaneous seizures, the clinical relevance
      of these studies has been questioned. The purpose of this study was to establish
      that cells genetically engineered to produce gamma-aminobutyric acid (GABA) could
      suppress spontaneous seizures in an accepted model of temporal lobe epilepsy.
      METHODS: Conditionally immortalized neurons were engineered to produce GABA under
      the control of tetracycline. These cells were transplanted into the substantia
      nigra of spontaneously seizing animals. After transplantation, the animals were
      monitored for 3 days immediately after surgery and again for 3 days beginning 7-8
      days after surgery. Seizures and epileptiform spikes were recorded and later
      analyzed with detection software combined with video monitoring. RESULTS: Animals
      that received genetically engineered GABA-producing cells had significantly fewer
      spontaneous seizures than did animals that received control cells, or animals
      that received GABA-producing cells plus doxycycline at the observation period
      starting 1 week after transplantation. A significant suppression of epileptiform
      spikes also was noted between the group that received GABA-producing cells and
      the group that received the same cells but were given doxycycline. The engineered
      cells show evidence of integration with the host but limited survival.
      CONCLUSIONS: These data demonstrate that genetically engineered cells have the
      ability to suppress spontaneous seizures when transplanted into seizure
      modulating nuclei. This is an important step toward defining a clinical potential
      for this approach in epilepsy. The fact that the gene of interest can be
      regulated suggests that individualizing transplant therapy may be possible.

PMID- 14692902
TI  - Fate of newborn dentate granule cells after early life status epilepticus.
AB  - PURPOSE: To determine the fate of newborn dentate granule cells (DGCs) after
      lithium-pilocarpine-induced status epilepticus (SE) in an immature rat. METHODS:
      Postnatal day 20 (P20) rats were injected with lithium and pilocarpine to induce
      SE, and then with bromodeoxyuridine (BrdU) 4, 6, and 8 days later (P24, 26, and
      28), and killed 1 day (P29), 1 week (P34), and 3 weeks (P50) after the last dose
      of BrdU for cell counts. Immunohistochemistry and TUNEL staining were performed
      to assess the fate of newborn DGCs. RESULTS: Pilocarpine-treated animals had
      significantly more BrdU-labeled DGCs than did littermate controls at all times.
      The day after the final BrdU injection (P29), sixfold more cells were found in
      pilocarpine-treated animals than in controls, which was reduced to threefold, 3
      weeks later. A decrease in the BrdU-labeled cell density was noted from P29 to
      P50 in the control and pilocarpine-treated animals. Evidence of DGC cell death
      was seen in pilocarpine and control animals, with threefold more TUNEL-positive
      cells in the pilocarpine-treated than in the control animals at P29. The
      surviving newborn DGCs became mature neurons; expressing the neuronal marker NeuN
      in both control and pilocarpine-treated animals. CONCLUSIONS: These findings
      suggest that SE during postnatal development increases the birth and death of
      DGCs. A subset of the newborn DGCs survive and mature into dentate granule
      neurons, resulting in an increased population of immature DGCs after SE that may
      affect hippocampal physiology.

PMID- 14692903
TI  - Pregabalin add-on treatment: a randomized, double-blind, placebo-controlled, dose
      response study in adults with partial seizures.
AB  - PURPOSE: To evaluate pregabalin (PGB), 150 mg/day, and PGB, 600 mg/day, as an add
      on treatment for patients with refractory partial seizures concurrently treated
      with one to three anticonvulsants (AEDs). METHODS: An international (13
      countries), multicenter (45 centers), 12-week, double-blind, randomized study in
      which patients with partial seizures received placebo (n = 96); PGB, 150 mg/day
      (n = 99); or PGB, 600 mg/day (n = 92); given 3 times a day (t.i.d.). The primary
      efficacy criterion was reduction in seizure frequency during treatment as
      compared with baseline, as measured by RRatio, the symmetrical percentage change
      in seizure rates determined from daily seizure diaries. The RRatio between the 8
      week baseline (pretreatment phase) and the 12-week treatment period were compared
      between each of the PGB groups and the placebo group by using an analysis of
      variance analysis of the intent-to-treat population. RESULTS: PGB, 150 mg/day and
      600 mg/day, were both significantly more effective than placebo in reducing the
      RRatio [-11.5 (p = 0.0007) and -31.4 (p < or = 0.0001), respectively, vs. 0.9].
      These RRatio values correspond to seizure-frequency reductions from baseline of 
      1.8, 20.6, and 47.8% for placebo, 150 mg/day, and 600 mg/day, respectively. PGB
      efficacy was significantly dose related (p < or = 0.0001). Secondary efficacy
      variables corroborated the findings of the primary analysis. Significantly more
      patients were responders (> or =50% reduction in seizure frequency) in the PGB,
      600 mg/day (43.5%), group than in the placebo group (6.2%) (p < or = 0.001). PGB
      was well tolerated. Dose-related, treatment-emergent adverse events (> or =10%),
      mostly mild or moderate in intensity, were somnolence, dizziness, ataxia,
      diplopia, and weight gain. The withdrawal rate due to adverse events was 10% of
      patients at 150 mg/day and 18.5% of patients at 600 mg/day, compared with 6.2% of
      patients receiving placebo. CONCLUSIONS: PGB, 150 mg/day and 600 mg/day, is
      highly effective and well-tolerated add-on therapy in patients with partial
      seizures.

PMID- 14692904
TI  - Implementation strategies for a Scottish national epilepsy guideline in primary
      care: results of the Tayside Implementation of Guidelines in Epilepsy Randomized
      (TIGER) trial.
AB  - PURPOSE: To determine the effectiveness of two dissemination and implementation
      strategies to implement a national guideline for epilepsy management in primary
      care settings. METHODS: Three-arm cluster-randomized controlled trial. The
      participants were general practitioners from 68 practices in Tayside, Scotland,
      and 1,133 of their patients with self-reported epilepsy treated with
      antiepileptic medications (AEDs). Practices were randomized blind to a control,
      intermediate, or intensive intervention. CONTROL: Postal dissemination of a
      nationally developed clinical guideline. Intermediate intervention: Postal
      dissemination of the guideline supported by interactive, accredited workshops,
      and dedicated, structured protocol documents. Intensive intervention:
      Intermediate intervention plus a nurse specialist who supported and educated
      practices in the establishment of epilepsy review clinics. The primary outcome
      was the SF-36 health-related quality-of-life instrument. Secondary measures were
      a battery of prevalidated epilepsy-specific quality-of-life instruments. These
      were administered at baseline and after the intervention phase. Process of care
      was assessed by case-note review on number of review meetings and counseling
      sessions for epilepsy before and after the interventions. RESULTS: None of the
      intervention groups showed any change in the primary or secondary outcome
      measures or process-of-care measures. CONCLUSIONS: None of the intervention
      strategies led to improvements in patient quality of life or quality of epilepsy
      care. Further research is needed to discover why the interventions failed, to
      identify barriers to adoption of guidelines, and to develop strategies that might
      improve implementation and uptake in the future.

PMID- 14692905
TI  - Ictal pleasant sensations: cerebral localization and lateralization.
AB  - Ictal pleasant feelings are a rare sign of focal epilepsies. The most popular
      description was performed by Dostojevskij, who reported an aura by Myshken in one
      of his books. No convincing evidence has been published concerning the cerebral
      localization of ictal happiness. In this study, the findings of 11 patients with
      ictal pleasant feelings are described. In eight patients, the origin of the focal
      epileptic activity was found in the temporal lobe (most often temporal inferior
      basal); in three patients, frontal or parietal lobe in addition to temporal lobe
      involvement was found. According to our findings ictal happiness is a localizing
      sign pointing to the ictal involvement of temporal mesiobasal areas.
      Lateralization to the right temporal lobe was found in seven and to the left
      temporal lobe in four patients.

PMID- 14692906
TI  - Usefulness of [11C]methionine PET in the diagnosis of dysembryoplastic
      neuroepithelial tumor with temporal lobe epilepsy.
AB  - PURPOSE: We assessed the diagnostic value of [11C]methionine (MET) positron
      emission tomography (PET) in the differential diagnosis of dysembryoplastic
      neuroepithelial tumors (DNETs) among benign tumors associated with temporal lobe
      epilepsy (TLE). METHODS: This series consisted of seven TLE patients with benign
      tumors in the temporal lobe. After MET-PET study, all seven patients underwent
      tumor resection along with focus excision. The uptake of tracers was evaluated by
      the lesion-to-contralateral ratio (L/C ratio) and the standardized uptake value
      (SUV). We also assessed the relation between MET uptake and proliferation
      capacity observed in the surgical specimens. RESULTS: Whereas four patients with
      DNETs did not show high MET uptake visually, the ganglioglioma and gliomas of the
      remaining three patients were identified as high-MET-uptake lesions. In the
      DNETs, the SUV ranged from 1.03 to 1.41, and the L/C ratio ranged from 0.99 to
      1.14. MET uptake was significantly lower in the patients with DNETs than in the
      patients with ganglioglioma and brain gliomas (SUV, p = 0.045; L/C ratio, p =
      0.0079). The Ki-67 labeling index was 4% in one patient with DNET and 5% in one
      patient with pleomorphic xanthoastrocytoma (higher labeling index). The higher
      labeling index was not related to high MET uptake based on the SUV (p = 0.91) and
      L/C ratio (p = 0.38). CONCLUSIONS: Negative MET uptake in benign temporal lobe
      tumors with TLE is consistent with a preoperative diagnosis of DNET.

PMID- 14692907
TI  - Indices of resective surgery effectiveness for intractable nonlesional focal
      epilepsy.
AB  - Among 70 patients with intractable focal epilepsy and no specific lesion, as
      determined by both MRI (magnetic resonance imaging) and histopathology, outcome
      after resective surgery was polarized: 26 (37%) became seizure free (SF), and 27
      (39%) were not helped. Eighteen (42%) of 43 standard temporal resections rendered
      patients SF, somewhat more than eight (30%) of 27 other procedures. To seek
      reliable prognostic factors, the subsequent correlative data compared features of
      the 26 SF patients with those of the 27 not helped. Although ictal semiology
      guided the site of surgical resection, it and other aspects of seizure and
      neurologic history failed to predict surgical outcome. However, two aspects of
      preoperative scalp EEGs correlated with SF outcomes: (a) among 25 patients in
      whom >50% of clinical seizures arose from the later resected lobe and no other
      origins, 18 (72%) became SF compared with seven (28%) of 25 with other ictal
      profiles; (b) 13 (93%) of 14 temporal lobe patients whose interictal and ictal
      EEGs lacked features indicative of multifocal epileptogenesis became SF compared
      with five (33%) of 15 with such components. The considered need for subdural (SD)
      EEG reduced SF outcome from 18 (90%) of 20 patients without SD to eight (24%) of
      33 with SD; this likely reflected an insufficient congruity of ictal semiology
      and interictal and ictal scalp EEG for localizing epileptogenesis. Within this SD
      group, >50% of clinical seizure origins from a later resected lobe increased SF
      outcome somewhat: from two (14%) of 14 without this attribute to six (40%) of 15
      with it; 100% of such origins increased SF outcome from two (12%) of 16 to six
      (46%) of 13.

PMID- 14692908
TI  - The relative influence of epileptic EEG discharges, short nonconvulsive seizures,
      and type of epilepsy on cognitive function.
AB  - PURPOSE: This study addressed whether cognitive impairment in children with
      epilepsy is caused by disease-related stable factors, such as the type of
      epilepsy, or by acute effects of paroxysmal epileptic activity such as epileptic
      EEG discharges. We studied a nonselected group with short nonconvulsive seizures,
      as these seizures may elude detection and may therefore persist over a longer
      period. In this group, the diagnostic issue is to differentiate between the
      combined effects of several epilepsy-related factors on cognition. METHODS: All
      children were assessed with 32-channel EEG, synchronized with a computerized
      cognitive test system and a video-monitoring system. Recording time was 2 h. The
      primary inclusion criteria were unclear seizures and fluctuations in cognitive
      performance and/or frequent epileptic EEG discharges in a recent EEG. RESULTS:
      One hundred fifty-two patients met the inclusion criteria; 31 patients appeared
      not to have a diagnosis of epilepsy and were used as a nonepilepsy control group.
      Our results show that type of epilepsy has an impact on stable cognitive
      functions, such as educational achievement. Paroxysmal epileptic activity (acute
      effects of seizures and epileptic EEG discharges) affects primarily transient
      mechanistic cognitive processes (alertness, mental speed). CONCLUSIONS: These
      results suggest that the effects of paroxysmal epileptic activity on transient
      cognitive mechanisms may accumulate over time and consequently affect the more
      stable aspects of cognitive function such as educational achievement. The
      clinical relevance is that early detection of the cognitive impact of seizure
      related activity and subsequent treatment may prevent its detrimental impact on
      cognitive and educational development.

PMID- 14692909
TI  - Depression and altered quality of life in women with epilepsy of childbearing
      age.
AB  - PURPOSE: To calculate the prevalence of depression in a referral population of
      women of childbearing age, to define the factors associated with depression, and
      to assess health-related quality of life (HRQOL) in the same population. METHODS:
      The 642 consecutive women with epilepsy aged 18-55 years were enrolled by 40
      neurologists over an 8-month period and asked to give details on selected
      demographic and clinical features regarding the disease, any associated clinical
      condition, and any drug treatment. Depression was diagnosed by using the Hamilton
      depression scale and HRQOL was measured through the SF-36 form. Demographic,
      clinical, and therapeutic risk factors for depression were searched for within
      the study population. RESULTS: Depression (any severity) was present at interview
      in 242 women, giving a prevalence rate of 37.7%[95% confidence interval (CI),
      33.9-41.6]. Mild depression was reported by 18.5% of women, moderate depression
      by 8.6%, major depression by 10.3%, and severe depression by 0.3%. Factors found
      to be independently associated with depression (any severity) included treatment
      of associated conditions [relative risk (RR), 1.5; 95% CI, 1.2-1.8), concurrent
      disability (RR, 1.3; 95% CI, 1.0-1.6), seizures in the preceding 6 months (RR,
      1.4; 95% CI, 1.1-1.7), and being unemployed or a housewife (RR, 1.3; 95% CI, 1.0
      1.5). Factors associated with moderate to severe depression included treatment
      for associated conditions (RR, 2.0; 95% CI, 1.4-2.7), seizures in the preceding 6
      months (RR, 1.7; 95% CI, 1.2-2.5), and being unemployed or a housewife (RR, 1.6;
      95% CI, 1.1-2.2). Compared with normal women of similar age, patients with
      epilepsy tended to present lower scores for each HRQOL domain (mostly Role
      Physical, General Health, Social Functioning, and Role Emotional). However, when
      the analysis was limited to nondepressed women with epilepsy, any difference
      disappeared. CONCLUSIONS: Women with epilepsy of childbearing age are at high
      risk of depression. Factors associated with depression include lack of
      occupation, the presence of an underlying disabling condition (with treatment),
      and the severity of epilepsy. Compared with the general population, depressed
      women have greater impairment of HRQOL with epilepsy, which reflects the
      physical, social, and emotional implications of the disease.

PMID- 14692910
TI  - Morbidity in patients with epilepsy: type and complications: a European cohort
      study.
AB  - PURPOSE: To investigate the risk of illnesses in a cohort of patients with
      epilepsy and in matched nonepilepsy controls, by type and complications. METHODS:
      A total of 951 children and adults with idiopathic, cryptogenic, or remote
      symptomatic epilepsy and 904 matched controls seen in secondary and tertiary
      centers in eight European countries (England, Estonia, Germany, Italy, the
      Netherlands, Portugal, Russia, Slovenia) were followed prospectively for 17,484
      and 17,206 person-months and asked to report any spontaneous complaint requiring
      medical attention (illness), its type and complications (hospitalization, absence
      from work or school, medical action). Risk assessment was done by actuarial
      methods, relative risks (RR), and 95% confidence intervals (CIs). RESULTS: During
      the study period 644 patients (68%) and 504 controls (56%) reported an illness (p
      < 0.0001); 30% were seizure related. The cumulative probability of illness at 12
      and 24 months was 49 and 86% in the cases and 39 and 75% in the controls (p <
      0.0001). The largest differences regarded disorders affecting the nervous system
      (NS) (RR, 3.3; 95% CI, 2.3-4.2) and ear, nose, and throat (ENT) (RR, 1.3; 95% CI,
      1.0-1.6). In patients with epilepsy, an NS illness was more likely to be followed
      by hospital admission, work absence, or medical intervention. All risks were
      significantly reduced after excluding seizure-related events. CONCLUSIONS:
      Patients with epilepsy are at higher risk of NS and ENT illnesses and
      complications than the general population. However, the risk of illness is
      significantly reduced when seizure-related events are excluded.

PMID- 14692911
TI  - Motor responses to afferent stimulation in juvenile myoclonic epilepsy.
AB  - PURPOSE: To document whether the mechanisms responsible for myoclonic jerks in
      juvenile myoclonic epilepsy (JME) are similar to those causing other forms of
      myoclonus. METHODS: We studied somatosensory evoked potentials, the conditioning
      effect of cutaneous afferents on motor potentials evoked by transcranial magnetic
      stimulation (TMS), and intracortical inhibition and facilitation in response to
      paired TMS in a group of nine patients with JME and 20 normal controls. RESULTS:
      Intracortical inhibition was abnormal, whereas cortical somatosensory evoked
      potentials and TMS conditioned by cutaneous afferents were unaltered in JME
      patients. CONCLUSIONS: Abnormal processing of cutaneous afferents would not
      appear to contribute to myoclonus in JME.

PMID- 14692912
TI  - Pharmacorefractory status epilepticus due to low vitamin B6 levels during
      pregnancy.
AB  - We report a patient with pyridoxine-dependent epileptic seizures during early
      childhood. She had been completely seizure free for 23 years until she became
      pregnant. During the week 14 of her pregnancy, status epilepticus developed and
      was refractory to antiepileptic drugs but responded to intravenous administration
      of vitamin B6. Vitamin B6 levels were found to be decreased during pregnancy,
      although the patient reported continued and regular oral supplementation.
      Possible reasons for decreased vitamin B6 levels leading to status epilepticus
      are discussed.

PMID- 14692913
TI  - Functional MRI and Wada determination of language lateralization: a case of
      crossed dominance.
AB  - The Wada test has historically been the conventional procedure for determining
      language lateralization before neurosurgery. However, functional magnetic
      resonance imaging (fMRI) offers a less invasive alternative to the Wada
      procedure. Research indicates that the two techniques used together may provide
      comparable, and sometimes complementary, information that results in improved
      prediction of postsurgical language ability. We present a case in which use of
      fMRI in conjunction with Wada testing provided complementary information about
      language lateralization before neurosurgical resection of a mesial temporal
      subependymoma for seizure control in a patient with schizencephaly.

PMID- 14692914
TI  - Levetiracetam reduces spike-wave density and duration during continuous EEG
      monitoring in patients with idiopathic generalized epilepsy.

PMID- 14692915
TI  - Absence epilepsy with onset before age three years: could this be Glut-1
      deficiency syndrome (De Vivo syndrome)?

PMID- 14692916
TI  - In memoriam. Peter Kellaway, Ph.D. 1920-2003.

PMID- 14692918
TI  - Enhancement of in vitro hair shaft elongation in follicles stored in buffers that
      prevent follicle cell apoptosis.
AB  - BACKGROUND: Viability and survival of stored micrografts during hair follicle
      transplantation are important limitations of micrograft transplantation
      procedures. In this study, we investigated the effect of different storage
      solutions and inhibitors of apoptotic cell death (ACD) on hair follicle cell
      viability by measuring in vitro hair shaft elongation (HSE) for 5 days. METHODS:
      Micrografts from informed patients undergoing routine micrograft transplantation
      were stored for 5 hours at room temperature in phosphate-buffered salt solution
      (PBS) or HEPES-buffered Dulbecco's modified Eagle's medium (DMEM), containing
      different concentrations of the ACD-inhibitors aminoguanidine (AMG), hormones
      (insulin, hydrocortisone), 14,15-epoxy-eicosatrienoic acid (14,15-EET), or
      combinations of these. RESULTS: In vitro, HSE was significantly increased in
      micrografts stored in DMEM compared with PBS (2.3%+/-0.6% vs. 28.4%+/-3.9%,
      P<0.0001). DMEM supplemented with AMG (10 microg/mL) or 14,15-EET (1 ng/mL)
      further increased in vitro HSE (33.9%+/-7.1%, p=0.01, and 32.8%+/-6.1%, P=0.02,
      respectively). Evaluation of ACD in stored micrografts, performed by
      determination of cytoplasmic histone-associated DNA fragments, confirmed the
      results found by HSE. ACD was detectable after a 36-hour culture in serum
      containing medium and was higher in micrografts stored in PBS compared with
      micrografts stored in DMEM (A405nm/A492nm: 1.63+/-0.21 vs. 1.42+/-0.07,
      respectively; P<0.01). The addition of AMG further decreased serum-induced ACD in
      the micrografts (DMEM 1.42+/-0.07 vs. DMEM/AMG 0.90+/-0.11, P<0.0001).
      CONCLUSION: Our study demonstrated an important role of ACD in micrograft
      transplantation surgery. Preconditioning of micrografts with storage buffers
      containing inhibitors of ACD could prevent serum-induced ACD after
      transplantation and might increase the viability of micrografts and the clinical
      outcome in micrograft transplantation.

PMID- 14692919
TI  - Microfoam ultrasound-guided sclerotherapy of varicose veins in 100 legs.
AB  - OBJECTIVE: To demonstrate the efficacy of duplex-guided foam sclerotherapy
      measured against patient symptom relief and quality of life. METHODS: An analysis
      was performed of 100 randomly chosen legs with varicose veins treated with
      ultrasound-guided foam sclerotherapy with a mean follow-up of 22.5 months.
      RESULTS: An average number of 2.1 treatments using an average of 8.7 mL of foam
      sclerosing solution were required to close incompetent varicose veins. Thirty-one
      percent of leg varicose veins required a second treatment at 3 months; 100% of
      patients felt that their legs were successfully treated with resolution of all
      symptoms in 85% and resolution in all varicose veins in 92%. CONCLUSION:
      Ultrasound-guided foam sclerotherapy is effective in treating varicose veins with
      high patient satisfaction with results and improvement in quality of life.

PMID- 14692920
TI  - Long-pulsed 1064-nm Nd:YAG laser-assisted hair removal in all skin types.
AB  - BACKGROUND: Although there are several different laser systems available for the
      reduction of unwanted hair, no single system has been shown to be superior in
      providing safe and effective hair removal in every skin type. The purpose of this
      study was to evaluate the safety and efficacy of a high-energy, long-pulsed, 1064
      nm Nd:YAG laser with a contact cooling device for hair removal in skin phototypes
      I-VI. METHODS: Thirty-six adult patients (skin phototypes I-VI) with dark
      terminal facial or nonfacial hair were treated with a long-pulsed Nd:YAG laser
      (1064 nm, 10-mm spot size, fluence of 30 to 60 J/cm2). The selected pulse
      duration was dependent on the skin type of the patient: Skin types I/II, III/IV,
      and V/VI received 10, 20, and 30 ms, respectively. Three consecutive laser
      treatments were delivered to 36 skin sites at 4- to 6-week intervals. Hair counts
      and photographic evaluations of skin sites were obtained at baseline, immediately
      before each treatment session, and at 1, 3, and 6 months after the final laser
      treatment. RESULTS: Peak hair reduction was observed 1 month after the series of
      laser treatments with a mean hair reduction ranging from 58% to 62% on facial
      sites and 66% to 69% on nonfacial sites. At 6 months after a series of three long
      pulsed Nd:YAG laser treatments, a mean hair reduction of 41% to 46% on the face
      and 48% to 53% on the body was found depending on the skin phototype. Adverse
      reactions included mild to moderate treatment pain, short-term erythema, and rare
      occurrences of transient pigmentary alteration without scarring. CONCLUSION: The
      long-pulsed 1064-nm Nd:YAG laser with contact cooling is a safe and effective
      method of hair reduction in patients of all skin types. Side effects were limited
      and transient.

PMID- 14692921
TI  - Moist exposed therapy: an effective and valid alternative to occlusive dressings
      for postlaser resurfacing wound care.
AB  - BACKGROUND: Laser resurfacing has now become an accepted and important component
      of facial rejuvenation. With the introduction of computerized scanning systems,
      the actual laser resurfacing technique has been greatly simplified; however, the
      final outcome still depends to a large extent on the efficiency of the postlaser
      wound care in promoting wound healing and preventing early and late
      complications. It has been repeatedly confirmed that a moist environment is the
      single most important external factor affecting the rate of re-epithelialization.
      Occlusive moisture-retentive dressings, however, are difficult to apply and
      maintain in position and may as well be complicated by serious infections.
      OBJECTIVE: Moist exposed burn ointment has been shown to maintain adequate
      moisture for optimal healing by frequent ointment application without the need
      for a secondary overlying dressing. It would be ideal for postoperative laser
      care. METHODS: Twenty-eight consecutive patients treated with coherent ultrapulse
      CO2 laser in Toulouse, France, were included in the trial. Moisture-retentive
      ointment was applied over the treated areas every 4 to 6 hours. Healing was
      assessed clinically and with repeated transepidermal water loss measurements.
      Swab cultures were taken, and pain was evaluated with a visual analog scale.
      Colorimetric analysis of pictures taken was statistically compared with picture
      analysis of 20 patients treated earlier with an occlusive dressing. RESULTS:
      Uneventful timely healing occurred in all patients with minimal pain and
      discomfort. Healing with moist exposed therapy resulted in faster recovery of
      cutaneous erythema, as evidenced by colorometry. CONCLUSION: Moist exposed burn
      ointment application can be safely considered a good and valid alternative to
      occlusive dressings for postoperative laser care.

PMID- 14692922
TI  - Chemical matricectomy with 10% sodium hydroxide for the treatment of ingrowing
      toenails.
AB  - BACKGROUND: In the last decades, phenol cauterization has been widely used with
      high success rates for the treatment of ingrowing toenails. However,
      unpredictable tissue damage and prolonged healing time are the disadvantages of
      this technique. Sodium hydroxide is an alternative chemical agent that causes
      less tissue damage. OBJECTIVE: In this study, long-term results and postoperative
      morbidity of two sodium hydroxide chemical matricectomy procedures carried out by
      different application times have been investigated. METHODS: A total of 156
      partial chemical matricectomy procedures were performed with 10% sodium hydroxide
      in 60 patients divided into two groups. The first group (80 nail sides) received
      a 2-minute application of sodium hydroxide, whereas the second group (76 nail
      sides) received a combination of curettage of the lateral matrix area and 1
      minute application of sodium hydroxide. Postoperative pain, drainage, and tissue
      damage were evaluated 2 days after the operation and at three more visits with
      weekly intervals. Long-term success rates of the methods were evaluated on the
      6th month and at a further visit with a mean time of 16.83+/-2.18 months (range,
      13 to 20). RESULTS: Partial matricectomy with 10% sodium hydroxide was found to
      be 100% successful in both of the groups (P>0.05). Postoperative pain and tissue
      damage were either absent or minimal in the great majority of the patients with
      no statistical difference between the two groups (P>0.05). On the 2nd day, more
      patients in the first group experienced mild drainage than the patients in the
      second group (P=0.001), but in the following control visits, this difference
      disappeared. CONCLUSION: Matricectomy with 10% sodium hydroxide, either applied
      for 2 minutes or 1 minute combined with curettage, is equally effective in the
      treatment of ingrowing toenails with high success rates and minimal postoperative
      morbidity.

PMID- 14692923
TI  - Pyruvic acid peels for the treatment of photoaging.
AB  - BACKGROUND: Pyruvic acid (CH3-CO-COOH), an alpha-keto-acid, has been recently
      used as a medium chemical peeling agent in subjects with inflammatory acne,
      moderate acne scars, greasy skin, actinic keratosis, and warts. OBJECTIVE: The
      aim of our study was to evaluate the efficacy and tolerability of 50% pyruvic
      acid on moderately photodamaged facial skin. METHODS: We treated 20 patients with
      four peeling sessions at 4-week intervals. We evaluated the patients clinically,
      and in order to obtain an objective assessment of the effect of pyruvic acid on
      pigmentary components of the skin, erythema and hyperpigmentation response were
      measured in all the patients before and after treatment using a Minolta Tri
      Stimulus Colorimeter II. RESULTS: The clinical evaluation of the patients after
      the peeling sessions demonstrated a smoother texture, less evident fine wrinkles,
      and evident lightening of hyperpigmentations (freckles and lentigines). In fact,
      chemical peels cause a thinning of the epidermis and a thickening of the dermis.
      The patients treated reported very limited or no discomfort in the postpeel
      period. CONCLUSION: Thus, 50% pyruvic acid peeling can be proposed as a safe and
      efficient treatment for moderate facial skin aging.

PMID- 14692924
TI  - Long-pulsed (6-ms) pulsed dye laser treatment of rosacea-associated
      telangiectasia using subpurpuric clinical threshold.
AB  - BACKGROUND: The pulsed dye laser (PDL), especially the 585-nm short-pulse width
      (450 micros) laser, has been extensively used in the treatment of facial
      telangiectasias. However, the resultant posttreatment purpura lasts for days and
      may not be cosmetically acceptable. OBJECTIVE: To examine the effect of long
      pulsed (6 ms) PDL at subpurpuric clinical threshold in the treatment of rosacea
      associated telangiectasia. METHODS: Twelve patients with rosacea-associated
      telangiectasia were recruited into the study. We used the 595-nm PDL at a pulse
      duration of 6 ms and titrated the fluence between 7 and 9 J/cm2 to produce
      immediate purpura lasting only a few seconds. Pretreatment cooling was achieved
      by cryogen spray. Assessment was made by comparing pretreatment and posttreatment
      photographs. Patients were evaluated 6 to 8 weeks after one PDL treatment.
      Results were reported as the percentage of reduction in the number of
      telangiectasias. Patients were asked for their own evaluation of improvement
      after treatment in terms of excellent, moderate, or poor outcome. Side effects
      such as pigmentary disturbance and scarring were also documented. RESULTS: Two of
      12 patients had more than 75% improvement. Another two had 50% to 75%
      improvement, and five had 25% to 50% improvement. Overall, 9 (75%) of 12 patients
      had more than 25% improvement after a single treatment of PDL. None of the
      patients reported any lasting posttreatment purpura or complications. CONCLUSION:
      The long-pulsed 595-nm PDL using subpurpuric clinical threshold was effective for
      treatment of rosacea associated telangiectasia.

PMID- 14692925
TI  - The emerging technique of the antiptosis subdermal suspension thread.
AB  - BACKGROUND: The improvement in and rejuvenation of facial features through the
      array of facioplasty techniques currently available remains intimately linked
      with the risk of complications associated with the cosmetic surgery procedure.
      The need for novel approaches to cosmetic facial surgery that achieve the desired
      end result for the patient while minimizing inherent risks and complications for
      the surgeon is acute. OBJECTIVE: To determine the efficacy of the Aptos subdermal
      suspension thread technique as an alternative to current facioplasty options
      through a studied series of this procedure. METHODS: Three hundred fifty Aptos
      procedures were performed on female patients as office-based, single-surgery
      procedures over a 43-month period. The procedure outcome was assessed in each
      case through patient interviews and surgeons' observations. RESULTS: Three
      hundred forty eight of the 350 Aptos procedures resulted in a completely
      satisfactory end point of facial rejuvenation. No major complications were
      reported, and mild asymmetry, ecchymosis, erythema, bleeding, visible threads,
      swelling, and discomfort were the only minor. Transient complications and side
      effects were noted. CONCLUSION: Our case study strongly suggests that the Aptos
      subdermal suspension thread technique provides an effective and much safer
      alternative to current facioplasty procedures for facial rejuvenation.

PMID- 14692926
TI  - Melanocyte transfer via epidermal grafts for vitiligo of labial mucosa.
AB  - BACKGROUND: Physiologic pigmentation of labial mucosa is seen regularly in dark
      skinned races. Vitiligo of nonkeratinized labial mucosa is often visible while
      talking and is a cosmetic problem. Medical therapies are not effective, and
      surgical therapies have not been tried for this site. OBJECTIVE: To study the
      efficacy of melanocyte transfer through contact of intact epidermal grafts with
      abraded labial mucosa. METHODS: Seven patients (five females and two males, age
      range from 17 to 29) with vitiligo of labial mucosa with or without involvement
      of vermilion were included in the study. Affected labial mucosa was dermabraded,
      and suction blister grafts were transferred over these areas. After 7 days, both
      dressing and grafts were removed, and photochemotherapy was started. RESULTS:
      Excellent color match and repigmentation were seen in all patients after 4 to 6
      weeks. CONCLUSIONS: The proposed modification in a well-established procedure of
      epidermal grafting is safe and effective. It is less time consuming and simpler
      than melanocyte culture, although the results are equivalent. There is no actual
      trans-plantation of keratinized skin, as it was removed.

PMID- 14692927
TI  - A comparative study of punch grafting followed by topical corticosteroid versus
      punch grafting followed by PUVA therapy in stable vitiligo.
AB  - BACKGROUND: Punch grafting followed by PUVA is an established therapy for stable
      vitiligo, but punch grafting followed by topical corticosteroid has never been
      evaluated. OBJECTIVE: The aim of this study was to evaluate the efficacy of
      topical corticosteroid in perigraft pigmentation and to compare it with perigraft
      pigmentation after PUVA in patients with stable vitiligo. METHODS: Fifty patients
      with stable vitiligo of various clinical types were subjected to punch grafting.
      In a randomized case study, these patients were divided into two groups: One
      group received post punch-grafting PUVA (group I) and the other group post punch
      grafting topical application of fluocinolone acetonide 0.1% (group II). During
      the follow-up period of 6 months, six patients were lost to follow-up, and two
      patients were excluded from the study; 42 patients were evaluated for pigment
      spread and side effects. RESULTS: In group I, the average pigment spread was 6.38
      mm, whereas in group II, it was 6.94 mm, showing a slightly higher pigment spread
      in group II, which was statistically not significant (P=0.301). There was no
      difference in response to therapy in patients having segmental vitiligo as
      compared with nonsegmental vitiligo. Cobblestoning, depigmentation of the grafts,
      infection, and graft displacement were the important side effects seen in some
      patients in both the groups. CONCLUSION: The study shows that the pigment spread
      with topical corticosteroid is comparable to that with PUVA. However, the studies
      with long-term follow-up are required to establish this. The advantages of
      topical corticosteroid are that its use is easy, less cumbersome, cheaper, and
      more cost effective than PUVA.

PMID- 14692928
TI  - Intralesional 5-fluorouracil as a treatment modality of keloids.
AB  - OBJECTIVE: To evaluate the efficacy and side effects of 5-fluorouracil (5-FU) as
      a therapeutic agent in the treatment of keloids of any duration or size. METHODS:
      This is a prospective, randomized, uncontrolled trial. Twenty-eight consecutive
      patients with keloids of varying size and duration were included in the study.
      All the patients were given intralesional 5-FU at weekly intervals for 12 weeks,
      and follow-up was done at 24 weeks. Improvement was assessed on a scale of five
      points, and the side-effects experienced were noted at each visit. RESULTS: The
      improvement was more than 50% in the majority of the patients, with no patient
      showing failure to therapy. The side effects commonly encountered were pain at
      the injection site, ulceration, and burning sensation. There was no recurrence of
      symptoms or the lesion during the follow-up period of 24 weeks in any of the
      patients. CONCLUSION: The efficacy of 5-FU is comparable to other singly used
      modalities as a treatment option for keloids. The lack of any serious side
      effects and the evidence of recurrence at 24 weeks of follow-up make this a
      promising modality.

PMID- 14692929
TI  - The incidences of chondritis and perichondritis associated with the surgical
      manipulation of auricular cartilage.
AB  - BACKGROUND: The cartilage and soft tissues of the ear are frequently employed as
      donor sites for tissue used in the repair of defects of the nose and external ear
      after Mohs surgery. Enthusiasm for using these auricular donor sites is
      occasionally tempered by surgeons' concerns for the development of Pseudomonal
      suppurative chondritis, a complication that has been described to follow
      cartilage manipulation. OBJECTIVE: To quantify the incidence of postoperative
      perichondritis and chondritis after Mohs reconstructions involving auricular
      cartilage manipulations. METHODS: We retrospectively reviewed 341 Mohs
      reconstructions that involved cartilage and soft-tissue donor sites located on
      the ear. Procedures included full-thickness skin grafts (295) harvested from the
      conchal bowl and flap repairs (46) incorporating cartilage batten grafts from
      conchal or anthelix donor sites. When the perichondrium was compromised, patients
      were routinely prescribed perioperative prophylactic antibiotics with Pseudomonal
      coverage. Postoperative examinations were performed at 1 week and 4 to 12 weeks.
      Patients not seen in clinic were interviewed by telephone regarding
      complications. RESULTS: Complete follow-up information was obtained in 337 of 341
      (98.8%) cases. Inflammatory perichondritis was observed in 19 (5.6%) patients.
      There were no cases of suppurative chondritis. CONCLUSION: The incidence of
      inflammatory perichondritis is low after Mohs reconstructions involving auricular
      cartilage manipulation. When prophylactic antibiotics and appropriate operative
      technique are used, the historic concern for suppurative chondritis associated
      with these procedures is unwarranted.

PMID- 14692930
TI  - Cold air analgesia in photodynamic therapy of basal cell carcinomas and Bowen's
      disease: an effective addition to treatment: a pilot study.
AB  - BACKGROUND: There is considerable interpatient variability in pain tolerance
      during and after treatment of skin cancer with photodynamic therapy (PDT).
      Additionally, erythema and edema are common, with mild crusting and healing over
      1 to 2 weeks. OBJECTIVE: To determine whether concurrent cold air analgesia
      improves the tolerability of PDT. METHOD: Twenty-six patients with two similar
      superficial skin cancers were treated with PDT. One lesion was treated with cold
      air analgesia and the other without. Patients rated their pain during treatment
      using the Wong Baker Faces Pain Scale and detailed duration of posttreatment
      pain. At week 2, the inflammatory response was assessed. RESULT: A statistically
      significant difference in the analgesia group was shown with respect to the mean
      duration of pain and the level of erythema after the first treatment as well as
      pain scores during the second treatment. CONCLUSION: Patient acceptance of PDT
      for treatment of nonmelanoma skin cancer is improved with lessened morbidity
      assessed with concurrent use of cold air analgesia to the treatment field.

PMID- 14692931
TI  - Segmental reconstruction of the face.
AB  - BACKGROUND: Aesthetic facial reconstruction requires understanding regional
      anatomy and tissue movement and the ability to use innovatively the tissue
      adjacent to the defect to create a reconstruction that preserves the function of
      the area and the cosmetic facial units. OBJECTIVE: Facial reconstruction after
      Mohs micrographic resection of nonmelanoma skin cancer confined to one cosmetic
      unit was compared with reconstruction of two or more units using techniques to
      place scars at the junction of cosmetic units with combinations of local flaps
      and grafts. Acute complications, function, and final appearance of the
      reconstruction were evaluated. METHODS: During a 10-year period, 500 cases
      acquired prospectively had facial surgical defects repaired. Tissue was removed
      to place the closure line at the junction of cosmetic units and was mobilized
      from within one cosmetic unit with primary closure or local advancement,
      rotation, or transposition flaps. When the defect bridged cosmetic units,
      segmental repair was performed with combinations of flaps and grafts placing
      scars at the junction of cosmetic units. Segmental repair often combined
      advancement flaps to restore contours with full-thickness skin grafts to prevent
      distortion in areas with minimal loss of contour. Scars were more often
      unfavorably placed with single flap repair within a cosmetic unit. There was more
      flap loss with single flap repair of a single unit than with segmental facial
      repair using a combination of flaps and/or grafts. CONCLUSION: Segmenting the
      wound into smaller units reflecting the underlying cosmetic units of the face was
      useful to develop a reconstruction plan to replace tissue with similar tissue and
      to provide consistently satisfying aesthetic results. Facial contours were
      restored without distorting surrounding structures.

PMID- 14692932
TI  - Vascular pattern in seborrheic keratoses and melanoma.

PMID- 14692933
TI  - The J-plasty advancement flap for reconstruction of malar cheek defects.

PMID- 14692934
TI  - Image is everything: pearls and pitfalls of digital photography and PowerPoint
      presentations for the cosmetic surgeon.
AB  - BACKGROUND: Cosmetic surgery and photography are inseparable. Clinical
      photographs serve as diagnostic aids, medical records, legal protection, and
      marketing tools. In the past, taking high-quality, standardized images and
      maintaining and using them for presentations were tasks of significant proportion
      when done correctly. Although the cosmetic literature is replete with articles on
      standardized photography, this has eluded many practitioners in part to the
      complexity. A paradigm shift has occurred in the past decade, and digital
      technology has revolutionized clinical photography and presentations. Digital
      technology has made it easier than ever to take high-quality, standardized images
      and to use them in a multitude of ways to enhance the practice of cosmetic
      surgery. PowerPoint presentations have become the standard for academic
      presentations, but many pitfalls exist, especially when taking a backup disc to
      play on an alternate computer at a lecture venue. OBJECTIVE: Embracing digital
      technology has a mild to moderate learning curve but is complicated by old habits
      and holdovers from the days of slide photography, macro lenses, and specialized
      flashes. Discussion is presented to circumvent common problems involving computer
      glitches with PowerPoint presentations. CONCLUSION: In the past, high-quality
      clinical photography was complex and sometimes beyond the confines of a busy
      clinical practice. The digital revolution of the past decade has removed many of
      these associated barriers, and it has never been easier or more affordable to
      take images and use them in a multitude of ways for learning, judging surgical
      outcomes, teaching and lecturing, and marketing. Even though this technology has
      existed for years, many practitioners have failed to embrace it for various
      reasons or fears. By following a few simple techniques, even the most novice
      practitioner can be on the forefront of digital imaging technology. By observing
      a number of modified techniques with digital cameras, any practitioner can take
      high-quality, standardized clinical photographs and can make and use these images
      to enhance his or her practice. This article deals with common pitfalls of
      digital photography and PowerPoint presentations and presents multiple pearls to
      achieve proficiency quickly with digital photography and imaging as well as avoid
      malfunction of PowerPoint presentations in an academic lecture venue.

PMID- 14692935
TI  - The running bolster suture for full-thickness skin grafts.

PMID- 14692936
TI  - The treatment of hypopigmentation after skin resurfacing.
AB  - BACKGROUND: Hypopigmentation has plagued all methods of skin resurfacing. Whether
      the physician uses chemical peels, dermabrasion or laser resurfacing
      hypopigmentation can develop. OBJECTIVE: To examine the pathogenesis and
      treatment of hypopigmentation after resurfacing. METHODS: Areas of
      hypopigmentation after skin resurfacing were blended in with laser-assisted
      chemabrasion (LACA). The process begins with preconditioning of the skin with
      vitamin A/glycolic skin conditioning lotions. Then the area is resurfaced with
      the LACA. This resurfacing usually requires three to four freeze-sand cycles to
      remove the areas of hypopigmentation associated with dermal fibrosis. The
      resurfaced skin is then occluded with a combination of polyethylene/silicone
      sheeting during the acute phase of wound healing. Ultraviolet photography and
      histologic examination were used to demonstrate the improvement in dermal
      fibrosis and hypopigmentation. RESULTS: The LACA improved areas of
      hypopigmentation in the 22 cases studied. Under occlusive wound dressings, the
      melanocytes migrated into the areas of hypopigmentation, and the wounds healed
      without extensive fibrosis. This produced a blending of skin color. CONCLUSION:
      It is possible with skin preconditioning, LACA, and occlusive wound healing to
      provide for a wound healing environment that blends in areas of hypopigmentation
      that have developed after previous skin resurfacing.

PMID- 14692937
TI  - Botulinum toxin for the treatment of facial flushing.
AB  - BACKGROUND: Facial flushing is a common problem that is encountered by fair
      skinned patients of Celtic and Northern European descent. Although usually
      transient in nature, some patients display a persistent reddened skin tone, with
      periods of increased erythema. Treatment of this condition is limited. OBJECTIVE:
      To describe a novel method for the treatment of persistent facial flushing.
      METHOD: We report a case of persistent facial flushing that was resistant to
      multiple pulsed dye laser treatments and was successfully treated with botulinum
      toxin A. RESULTS: The posttreatment appearance was dramatic, and the patient was
      highly satisfied with the cosmetic outcome. CONCLUSION: Botulinum toxin A can be
      used in small quantities to decrease persistent facial flushing temporarily.

PMID- 14692938
TI  - Successful treatment of a cosmetic tattoo using a combination of lasers.
AB  - BACKGROUND: Cosmetic tattoos are becoming more popular and are often composed of
      several colors. Tattoo pigments containing ferric oxide and titanium dioxide can
      change to a blue-black color after exposure to Q-switched lasers that can be
      permanent. OBJECTIVE: Using a patient who presented with rouge tattoos on the
      cheeks as an example, we describe a useful approach to laser treatment of
      cosmetic tattoos. METHODS: Test areas were done with the Q-switched Nd:YAG at
      both 532 and 1064 nm and with the pulsed-dye laser at 595 nm. RESULTS: Although
      an immediate blue-black color change occurred after treatment with the Nd:YAG at
      532 and 1064 nm, sequential treatments at 1064 nm produced a near complete
      clearance of the tattoos. The pulsed-dye laser was used to remove subtle pink
      tones. CONCLUSION: Performing small test areas before complete treatment and
      using several laser wavelengths throughout the course of therapy are essential to
      the successful treatment of cosmetic tattoos.

PMID- 14692940
TI  - Trichilemmal carcinoma: a rare cutaneous malignancy: a report of two cases.
AB  - BACKGROUND: Trichilemmal carcinoma is a rare cutaneous malignancy that usually
      occurs on the sun-exposed areas of older individuals. The lesion is usually
      solitary and may present as an exophytic or polypoid nodule that maybe
      hyperkeratotic with ulceration. OBJECTIVE: To present two cases of trichilemmal
      carcinoma, one occurring in a kidney transplantation patient. METHODS: Two case
      reports and a discussion of the rare carcinoma are presented. RESULTS: Both
      lesions were treated with Mohs micrographic surgery without sign of recurrence
      after several years. CONCLUSION: Trichilemmal carcinoma is a rare cutaneous
      malignancy that can be seen in both immunocompetent and immunosuppressed hosts.
      Mohs micrographic surgery should be considered among the surgical options to
      avoid a wide surgical excision in these patients.

PMID- 14692939
TI  - Superficial leiomyosarcoma treated with Mohs micrographic surgery.
AB  - BACKGROUND: Leiomyosarcoma (LMS) is a rare cutaneous malignancy with an
      infiltrative growth pattern and high risk of local recurrence (30-45%) with
      conventional wide excision. Mohs micrographic surgery (MMS) may offer an improved
      cure. OBJECTIVE: To illustrate by case reports the spectrum of clinical
      presentation of this rare neoplasm and management with MMS. METHODS: The outcomes
      of three cases of LMS treated by Mohs micrographic are described and compared
      with other cases in the medical literature. RESULTS: Three cases of LMS were
      excised using MMS. Two cutaneous tumors located on the trunk and arm were easily
      removed and have not recurred. The third tumor on the leg of an immunosuppressed
      patient demonstrated deep soft-tissue invasion that developed subsequent
      cutaneous metastases but no recurrence adjacent to the primary site. The patient
      remains disease free at 36 months after amputation below the knee. A total of 15
      cases of LMS treated by MMS are reported in the literature, including these
      cases, with an aggregate recurrence rate of 13%. CONCLUSIONS: The overall cure
      rate of leiomyosarcoma treated by MMS is 87%, which compares favorably to wide
      excision and offers the advantage of tissue sparing. Immunosuppression may
      promote aggressive tumor behavior. Deeply invasive tumors may result in cutaneous
      or distant metastases regardless of the method of excision.

PMID- 14692941
TI  - Intralesional interferon alpha-2b in the treatment of basal cell carcinoma and
      squamous cell carcinoma: revisited.
AB  - BACKGROUND: Intralesional interferon (IFN) alpha-2b has been shown to be a safe
      and effective mode of treatment for basal cell carcinoma and squamous cell
      carcinoma. Multiple studies published in the 1980s through the early 1990s have
      demonstrated the efficacy of intralesional interferon in the treatment of these
      malignancies. Unfortunately, this modality appears to be underused. OBJECTIVE:
      This article serves to remind dermatologists that in addition to cryotherapy,
      electrodesiccation, and surgical excision, intralesional IFN-alpha is an
      important part of the armamentarium in the treatment of nonmelanoma skin cancers.
      METHODS: In addition to a review of the literature, we present eight cases in
      seven patients successfully treated with intralesional IFN for basal cell
      carcinoma and squamous cell carcinoma. CONCLUSIONS: Its nonsurgical approach and
      excellent cosmetic results make IFNalpha-2b an attractive option for patients and
      an important alternative when other treatment modalities are impractical or
      contraindicated.

PMID- 14692942
TI  - Giant lipoma of the back.

PMID- 14692944
TI  - The role of positron emission tomography in the management of colorectal cancer.
AB  - Positron emission tomography (PET) is a functional imaging modality that has made
      the transition from the research environment to the clinical environment over the
      last 10 years. Its major role is in the field of oncology where it is being used
      increasingly in the management of several tumour types including colorectal
      cancer. This review aims to outline the current and future role of PET scanning
      in the field of colorectal cancer.

PMID- 14692945
TI  - Pre-operative radiotherapy for rectal carcinoma? Has the case really been made
      for short course pre-operative radiotherapy if surgical standards for rectal
      carcinoma are optimal?
AB  - Recent publications on early results of the Dutch trial on pre-operative
      radiotherapy combined with total mesorectal excision (TME) for resectable rectal
      cancer have initiated a major swing towards routine radiotherapy of this type.
      However, detailed analysis of the data so far published shows 23.3% microscopic
      margin involvement and 23.9% macroscopically poor specimens in a sample group.
      Since only mobile tumours were selected these figures are too high to validate
      the claim that the whole series represents 'standardized TME surgery'. The role
      of pre-operative radiotherapy for resectable rectal cancer undergoing optimal
      surgery therefore remains open. It may be expected that in future the individual
      indication for pre-operative radiotherapy will be based on the findings of pre
      operative modern fine slice high resolution magnetic resonance imaging (MRI).

PMID- 14692946
TI  - The prevalence of small, flat colorectal cancers in a western population.
AB  - OBJECTIVE: Small, flat colorectal cancers have been widely reported in the
      Japanese literature but are thought to occur rarely outside Japan. The aim of
      this retrospective cohort study was to clarify the prevalence of flat colorectal
      cancer in a Western population. METHODS: One thousand and twenty-six consecutive
      colonoscopies performed by a single experienced endoscopist were retrospectively
      analysed over a two-year period. The morphology, site and histological appearance
      of all documented colorectal cancers (CRC) were recorded. RESULTS: Forty-seven
      cases of CRC were detected, five of which (10%) demonstrated flat configuration.
      Flat cancers varied between 8 and 15 mm in diameter (mean 11 mm). Histologically,
      all flat lesions were moderately differentiated Dukes A adenocarcinomas. Two of
      these cancers contained no adenomatous component. CONCLUSION: This study confirms
      that small, flat colorectal cancers are not an uncommon finding at colonoscopy in
      Western patients. Compared to polypoid neoplastic lesions, flat cancers appear to
      undergo malignant change at a smaller size.

PMID- 14692947
TI  - Colo-rectal anastomotic leakage often masquerades as a cardiac complication.
AB  - OBJECTIVE: The aim of this study was to identify the mode of presentation of
      patients with clinical anastomotic leaks following restorative colorectal
      resection for carcinoma. PATIENTS AND METHODS: Prospective information was
      collected on all patients having restorative resection of colorectal cancer.
      These data were reviewed for a five-year period (1994-1998) to identify all
      patients who had suffered a clinical anastomotic leak and their notes were
      retrieved and reviewed. RESULTS: Three hundred and seventy-nine patients
      underwent restorative resection for colorectal cancer during the study period
      (178 female, 201 male), mean age 70 years (range 36-94). There were 22 (6%)
      clinical anastomotic leaks. Seven (32%) patients presented with obvious abdominal
      peritonitis. The remaining 15 (68%) were initially misdiagnosed. Thirteen (59%)
      patients were treated for cardiac symptoms, 1 (5%) patient for obstruction and 1
      (5%) for ascites. The delay in diagnosis ranged from 0 to 11 days (mean 4 days).
      For the whole series of 379 there were 30 patients who suffered cardiac symptoms
      (8%) 13(43%) of whom had an anastomotic leak. CONCLUSION: Patients who develop
      cardiac symptoms following restorative colorectal resection for carcinoma should
      have a water soluble enema as there is a 40% chance that they will have an
      anastomotic leak.

PMID- 14692948
TI  - Proctocolectomy and pelvic pouch--is a diverting stoma dangerous for the patient?
AB  - OBJECTIVE: A diverting loop ileostomy was previously considered mandatory for
      minimizing the effects of septic complications in pelvic pouch surgery. During
      the past decade there has been a trend towards omission of the loop ileostomy
      without obvious signs of increased numbers of pouch complications or impaired
      long-term function. The aim of the present study was to evaluate the risk of
      complications associated with the construction and closure of the loop ileostomy
      itself. PATIENTS AND METHODS: Complications following diverting loop ileostomies
      in 143 patients subjected to restorative pelvic pouch surgery during the period
      1983-97 were studied retrospectively by evaluation of case records. RESULTS: In
      the period between discharge after pelvic pouch surgery and closure of the loop
      ileostomy, 20 (14%) patients were hospitalized because of excessive stoma flow
      and 19 (13%) patients were treated for other surgical complications, of whom 10
      (7%) required surgical intervention. In the early postoperative period (within 30
      days) after closure of the loop ileostomy, 18 (13%) patients suffered
      complications necessitating surgery. Another 12 (8%) patients were hospitalized
      because of intestinal obstruction that could be treated conservatively.
      CONCLUSION: The proportion of complications associated with diverting loop
      ileostomies in pelvic pouch surgery was considerable. A randomised controlled
      multicentre study is ethically defensible and is recommended.

PMID- 14692949
TI  - Sulforaphane inhibits growth of a colon cancer cell line.
AB  - OBJECTIVE: The consumption of cruciferous vegetables has a protective effect on
      the development of colorectal cancer. The phytochemical Sulforaphane is an
      isothiocyanate found almost exclusively in cruciferous vegetables. We have
      studied the effect of Sulforaphane on cell proliferation of an HT-29 colon cancer
      cell line. MATERIALS AND METHODS: HT-29 colon cancer cells were cultured in 96
      well microtitre plates. Sulforaphane (in concentrations ranging from 0.01 to 0.1
      mmol) were added to the wells. Cell proliferation was measured using the
      colourimetric assay technique. RESULTS: The proliferation of colon cancer cells
      was significantly reduced by Sulforaphane at concentrations of >/=0.02 mmol.
      CONCLUSION: These findings may help explain the epidemiologically proven
      protective effect of vegetables against colon cancer.

PMID- 14692950
TI  - Direct appositional (no flap) closure of deep anal fistula.
AB  - OBJECTIVE: After sphincter-sparing core fistulectomy for deep anal fistula most
      surgeons advance a rectal mucosal flap to reinforce closure of the internal
      opening. Our own method having for many years been simple appositional closure
      the resulting series presented an opportunity for comparison. PATIENTS AND
      METHODS: From November 1987 to January 2001, 44 patients underwent 46 core
      fistulectomies with flap-less direct appositional closure in our unit. Records
      were kept prospectively. Twenty-six fistulae (in 28 patients) appeared healed at
      two to five months follow-up and the patients had been discharged. A full review
      was mounted in May 2001, when 16 of the healed patients could be contacted and
      questionnaires completed. Two patients were excluded from the study. RESULTS: The
      procedure failed in 16 patients initially and was found to have done so in two
      more at long-term follow-up (41% overall). Three patients had died and five could
      not be traced. CONCLUSION: Simple appositional closure after core fistulectomy
      for deep anal fistula seems inferior to methods using flap reinforcement.

PMID- 14692951
TI  - Randomised controlled clinical trial of stapled haemorrhoidectomy vs conventional
      haemorrhoidectomy; a three and a half year follow up.
AB  - OBJECTIVE: This article presents the results of a three and a half year follow up
      of patients recruited to a randomised controlled clinical trial comparing
      circumferential mucosectomy (stapled haemorrhoidectomy) vs conventional
      haemorrhoidectomy. METHODS: Patients were assessed in an outpatient setting to
      examine a number of outcome measures. RESULTS: Our data suggest that at the three
      and a half year follow up, there are no significant differences in outcome
      between the two groups. CONCLUSIONS: It will be important to review the long-term
      results of larger trials.

PMID- 14692952
TI  - Quality of life in patients with chronic anal fissure.
AB  - OBJECTIVE: Little is known about the quality of life in patients with the
      distressing symptoms of chronic anal fissure. This was a prospective study
      assessing the physical and mental health of fissure patients before and after
      topical treatment. PATIENTS AND METHODS: New patients attending the fissure
      clinic were recruited prospectively into the study over a 2-month period. On
      first appointment, patients were given 2 questionnaires to complete: the Short
      Form 36 Health Survey (SF-36) and a general questionnaire recording patients'
      demographic details, previous treatment, site and duration of fissure and
      symptoms on a visual analogue scale (VAS). Following an 8-week course of topical
      treatment, patients repeated the SF-36 and symptoms were again recorded on a VAS.
      Healing of fissure was noted. RESULTS: Fifty-four patients entered the study, of
      which 39 returned for follow-up; 16 male, 23 female; mean age 38.6 years (range
      17-80 years). Median duration of fissure was 6 months (3 months - 10 years).
      Higher VAS ratings for fissure pain were associated with worse scores for all
      aspects of health-related quality of life, including mental health (P < 0.001),
      bodily pain (P < 0.001), vitality (P < 0.006) and social functioning (P < 0.001).
      Compared to age and gender matched norms for the SF-36, fissure patients had more
      bodily pain (P < 0.001, Wilcoxon) and poorer health perceptions (P < 0.02,
      Wilcoxon). Gender did not affect any of the SF-36 subscales. However, females did
      report significantly more bleeding (P = 0.05). On follow-up, healing was complete
      in 27 patients (69%). Symptoms of pain, bleeding and irritation were all
      significantly reduced in this group. Repeating the SF-36 showed an improvement in
      bodily pain, role-physical functioning and vitality (P < 0.05). CONCLUSION:
      Successful nonsurgical treatment of chronic anal fissure leads to symptomatic
      improvement and beneficially affects health-related quality of life.

PMID- 14692953
TI  - Open-magnet MR defaecography compared with evacuation proctography in the
      diagnosis and management of patients with rectal intussusception.
AB  - OBJECTIVE: The aim of this study was to determine whether open-magnet magnetic
      resonance (MR) defaecography could provide more useful clinical information than
      evacuation proctography (EP) alone in the evaluation of a cohort of patients with
      full-thickness rectal intussusception and could assist in decisions concerning
      management. METHODS: Ten patients (4 male; median age 43, range 30-65) with
      symptomatic circumferential rectal intussusception diagnosed on EP, underwent
      open-magnet MR defaecography. Pathologies visible with each technique were
      recorded and 12 parameters of anorectal configuration and morphology measured and
      compared. RESULTS: There was discordance in the diagnosis of rectal
      intussusception in three cases. In another two patients, MR defaecography
      demonstrated mucosal descent only. Measurements of anorectal configuration and
      morphology were similar between techniques; only rectal size and lateral
      dimensions of the rectocoele were significantly different, being smaller on MR
      defaecography than EP. Two patients were shown on MR defaecography to have
      significant bladder descent and two female patients had significant vaginal
      descent. CONCLUSION: EP remains the first line investigation for the diagnosis of
      rectal intussusception, but may not distinguish mucosal from full-thickness
      descent. MR defaecography further complements EP by giving information on
      movements of the whole pelvic floor, 30% of the patients studied having
      associated abnormal anterior and/or middle pelvic organ descent. If surgery is
      planned for patients with rectal intussusception, MR defaecography provides
      useful information regarding the presence and degree of anterior pelvic
      compartment descent that may need to be addressed if a good functional outcome is
      to be achieved.

PMID- 14692954
TI  - Penile and clitoral stimulation for faecal incontinence: external application of
      a bipolar electrode for patients with faecal incontinence.
AB  - OBJECTIVE: The aim of this study was to assess the effect of a novel pudendal
      nerve stimulator on clinical and anorectal manometric parameters in patients with
      faecal incontinence. METHOD: Retrospective cohort analysis of consecutive
      patients presenting with faecal incontinence who had failed initial conservative
      treatment and were not suitable for surgical intervention in a university
      hospital incontinence clinic. Biofeedback using a pudendal nerve stimulator
      comprising a bipolar electrode applied to the base of the clitoris or penis.
      Electrical pulse voltage was self-titrated and defined periods of treatment were
      prescribed. Anorectal manometry and Cleveland incontinence scores were assessed.
      RESULTS: There was a significant reduction in incontinence symptom score after
      pudendal nerve stimulator treatment in the 42 patients treated and who had a
      complete set of data (median age 57 years (range 37-81); 39 female, 3 male). This
      was accompanied by significant improvements (P < 0.05) in anal sphincter tone,
      maximal tolerated rectal volume and the sustained rectoanal inhibitory reflex.
      CONCLUSIONS: An externally applied pudendal nerve stimulator improves symptoms
      and physiological evidence of faecal incontinence but long-term follow up is not
      available for these patients.

PMID- 14692955
TI  - Ano-rectal physiological changes after rubber band ligation and closed
      haemorrhoidectomy.
AB  - OBJECTIVE: The effect of treatment for haemorrhoids on ano-rectal physiology was
      studied in a prospective longitudinal follow-up study. METHODS: Thirty-six
      consecutive patients having II-III degree (Group I, 18 patients) or IV degree
      (Group II, 18 patients) haemorrhoids were studied. Group I underwent rubber band
      ligation while Group II underwent closed scissors haemorrhoidectomy. RESULTS:
      Patients in Group I had significantly lower maximum basal pressure (P < 0.05) and
      also significantly lower maximum squeeze pressure (P < 0.05) compared to Group II
      before treatment. Both basal and squeeze pressures dropped after
      haemorrhoidectomy (P < 0.001) whereas they remained unchanged after rubber band
      ligation (P > 0.1). The volume of first sensation was higher in Group II before
      treatment (P < 0.001) and remained so after treatment. Rectal compliance was
      higher (P < 0.005) in Group I before treatment. It increased significantly in
      both groups (P < 0.05, Group I; P < 0.001, Group II) after treatment.
      CONCLUSIONS: The results show a significant increase in anal pressures in
      constantly prolapsing (IV degree) haemorrhoids. Most of the physiological
      differences observed between the two groups were abolished after treatment. This
      suggests that these may be a consequence rather than a cause of haemorrhoids.

PMID- 14692956
TI  - Acute adrenal crisis in a patient treated with rectal steroids.

PMID- 14692957
TI  - Rectovaginal fistula after stapled haemorrhoidopexy.

PMID- 14692959
TI  - Universal leukoreduction and acute transfusion reactions: putting the puzzle
      together.

PMID- 14692960
TI  - Autoantibodies induced by blood transfusion.

PMID- 14692961
TI  - The effect of prestorage WBC reduction on the rates of febrile nonhemolytic
      transfusion reactions to platelet concentrates and RBC.
AB  - BACKGROUND: Febrile non-hemolytic transfusion reactions (FNHTRs) are a common
      complication of platelet concentrate (PC) and RBC transfusions, usually ascribed
      to cytokines released by WBCs and perhaps the platelets themselves during
      storage. Prestorage WBC reduction should abrogate the accumulation of these
      cytokines reducing the number of FNHTRs. STUDY DESIGN AND METHODS: A
      retrospective analysis of FNHTR to PCs and RBCs before universal WBC reduction
      (PrUR) (July 1997-January 1998 for PCs, July 1997-July 1999 for RBCs) and after
      its introduction (PoUR) (February 1998-August 2001 for PC, August 1999-August
      2001 for RBCs) was undertaken. All transfusion reactions were stratified based on
      component and date of reaction. Other adverse transfusion reactions were grouped
      into three periods: July 1997-January 1998, February 1998-July 1999, and August
      1999-August 2001. A chi-square test was performed to determine the significance
      of the differences between groups. RESULTS: In the PRUR group, there were: 231
      FNHTRs in 70,396 RBC units transfused (0.33%) and 29 FNHTRs in 6502 PC units
      transfused (0.45% percent). In the PoUR group, there were 136 FNHTRs in 72,949
      RBC units transfused (0.19%, p < 0.001) and 56 FNHTRs in 50,555 PC units
      transfused (0.11%, p < 0.001). Of the other adverse events, only TRALI reactions
      were significantly reduced. CONCLUSION: Prestorage WBC reduction significantly
      reduced the rate of FNHTRs to PCs and RBCs.

PMID- 14692962
TI  - Reduction of febrile but not allergic reactions to RBCs and platelets after
      conversion to universal prestorage leukoreduction.
AB  - BACKGROUND: Between January 1995 and November 1998, at Yale-New Haven Hospital,
      25 percent of RBCs transfused were processed through prestorage or bedside
      leukoreduction filters, chosen on a per patient basis (selective leukoreduction
      [SLR]). Between January 1995 and July 1999, 30 percent of platelet concentrates
      (PCs) were infused through bedside leukoreduction filters. In an attempt to
      decrease febrile nonhemolytic transfusion reactions (FNHTR), a change was made
      from SLR to universal prestorage leukoreduction (UPL) for RBCs between November
      1998 and December 1999 and for random donor PCs between July 1999 and January
      2000. FNHTR and allergic transfusion reactions (ATR) reported from January 1995
      through December 2002 were reviewed. STUDY DESIGN AND METHODS: For retrospective
      observational analysis, blood bank data were available on the number of RBCs and
      PCs transfused, percent products leukoreduced, and rate of FNHTR and ATR from
      1995 through December 2002. After dividing this time period into three phases
      (SLR, transition, and UPL), these data were evaluated using odds ratio (ORs) and
      Student's t tests. RESULTS: A total of 145,369 RBCs and 137,982 PCs (29,487 PC
      pools) transfused between January 1995 and December 2002 were evaluated. For
      RBCs, the relative FNHTR rate decreased 47.1 percent, from 0.34 percent (SLR) to
      0.18 percent (UPL) (p < 0.0001). ATR rates for RBCs showed 0.09 percent for both
      SLR and UPL groups (p > 0.05, NS). For PCs, the FNHTR relative rate decreased
      93.1 percent, from 2.18 percent for SLR to 0.15 percent for UPL (p < 0.0001).
      Rates for ATR were 0.49 percent (SLR) and 0.35 percent (UPL) (p > 0.05, NS).
      CONCLUSIONS: A significant decrease in the frequency of posttransfusion FNHTR,
      but not ATR, for RBCs and PCs followed introduction of 100-percent UPL. The data
      support the hypothesis that the practice of UPL of RBCs and PCs decreases the
      frequency of FNHTR and thus improves patient care over the practice of selective
      leukoreduction.

PMID- 14692963
TI  - Universal leukoreduction decreases the incidence of febrile nonhemolytic
      transfusion reactions to RBCs.
AB  - BACKGROUND: Febrile nonhemolytic transfusion reactions (FNHTR) is a relatively
      common complication associated with allogeneic transfusion. Because WBCs have
      been implicated in the mechanism of FNHTRs, it has been proposed that the
      transfusion of leukoreduced RBCs should be associated with a decreased incidence
      of FNHTRs. These reactions are generally not life threatening, but they are
      expensive in their management, evaluation, and associated blood-product wastage.
      Over the past several years, the proportion of leukoreduced RBCs has increased at
      Johns Hopkins Hospital in an effort to move toward complete leuko-reduction. A
      retrospective analysis is reported here of FNHTRs in RBC recipients as the
      inventory increased in percentage of leukoreduced RBC units. STUDY DESIGN AND
      METHODS: Between July 1994 and December 2001, all transfusion reactions (TRs)
      associated with the transfusion of allogeneic RBCs were retrospectively analyzed.
      Both computerized data and individual TR reports were reviewed. Patients who had
      both allergic and febrile features were included as part of both categories. TRs
      were reported as a percentage of total units transfused. Two time periods were
      selected for direct comparison. July to December 1994 represents the time period
      before the initiation of an increase in leuko-reduction. July to December 2001
      represents a time period when almost complete leukoreduction (99.5%) had been
      achieved. The TR data were compared between these two time periods, comparing a
      time before leuko-reduction to a time period after leukoreduction had been
      achieved. The trends in TRs over the entire 7.5-year period of July 1994 to
      December 2001 were also assessed. RESULTS: In the initial period before the
      initiative to move toward leukoreduction, 96 percent of our RBC inventory was non
      leukoreduced. In the study period after leukoreduction, 99.5 percent of our RBC
      inventory was leukoreduced. When comparing these two time periods, the incidence
      of FNHTRs decreased from 0.37 percent to 0.19 percent (p = 0.0008). The trend
      over the entire 7.5-year study period confirms the decrease in FNHTRs as the
      percentage of leukoreduced RBCs increased. The incidence of allergic TRs has
      remained unchanged over this time period. CONCLUSIONS: As our institution has
      increased its inventory of leukoreduced RBCs to approximately 100 percent,
      selective leukoreduced protocols have been discontinued. The incidence of FNHTRs
      has decreased significantly and the rate of allergic reactions has essentially
      remained unchanged. Leukoreduction is effective in decreasing FNHTRs associated
      with the transfusion of allogeneic RBCs.

PMID- 14692964
TI  - Leukoreduction in the setting of open heart surgery: a prospective cohort
      controlled study.
AB  - BACKGROUND: Proven clinical benefits of leukoreduced blood components include
      reduced febrile nonhemolytic transfusion reactions, alloimmunization against HLA
      antigens, and CMV transmission. Immunomodulatory effects of leukoreduction have
      also been postulated to play a significant role in the clinical outcome of open
      heart surgery. STUDY DESIGN AND METHODS: A prospective case control study was
      implemented in which all patients admitted over a 1-year period for open heart
      surgery at a single hospital were given leukoreduced blood products. Clinical
      outcomes were prospectively measured and compared to a historical cohort of
      patients from the previous year when leukoreduced blood products were not
      routinely used. RESULTS: A significant improvement in the mean postoperative
      length of stay was seen in the study group (N = 645) versus control group (N =
      501; 10.1 vs. 9.5 days; p = 0.005). No significant changes were seen in the rate
      of mediastinitis, operative mortality, or stay in the intensive care unit. There
      was no difference in the postoperative length of stay among study patients who
      did not receive transfusion (N = 308) versus control patients who did not receive
      transfusion (N = 296; 6.2 vs. 6.4 days; p = 0.104). CONCLUSIONS: The use of
      leukoreduced blood was associated with a decrease in the postoperative length of
      stay in the setting of open heart surgery. The mechanisms through which these
      changes in clinical outcomes are generated remain unknown.

PMID- 14692965
TI  - Preliminary validation of a new standard of efficacy for stored platelets.
AB  - BACKGROUND: Platelet preparation and storage systems, unlike those for RBC, lack
      an objective, absolute performance criterion to determine acceptability.
      Recently, a criterion based on paired comparison with the radiolabeled recovery
      and survival of "fresh" platelets has been proposed, namely, recovery = two
      thirds and survival = half of "fresh" platelets. STUDY DESIGN AND METHODS: Eleven
      normal subjects donated a unit of leukoreduced apheresis platelets using a
      standard, approved system. They received an aliquot radiolabeled with 111In or
      51Cr (random selection) 4 to 20 hours after donation and, using the other
      radioisotope, on Day 5 of storage. The recovery was calculated based on the
      injectate radioactivity. The survival was determined using the multiple-hit
      model. The area under the platelet survival curve was calculated using the COST
      program. RESULTS: Reinfusion of platelets less than 20 hours after collection
      resulted in a recovery of 74.7 +/- 12.3 percent and a survival time of 7.5 +/-
      1.1 days. Reinfusion on Day 5 resulted in a recovery of 58.2 +/- 12.0 percent and
      a survival time of 6.9 +/- 1.4 days, values that were 77.9 +/- 9.5 percent and
      91.8 +/- 16.1 percent of the observation using "fresh" platelets, respectively.
      The area under the curve using Day 5 platelets was 67.8 +/- 11.5 percent of that
      using "fresh" platelets. CONCLUSION: The proposed criterion for objective
      evaluation of platelet preparation and storage systems appears applicable to a
      commonly accepted approach, leukoreduced apheresis platelets stored in plasma for
      5 days, and merits evaluation using other collection, treatment, and storage
      systems.

PMID- 14692966
TI  - Evaluation of HTLV-I removal by filtration of blood cell components in a routine
      setting.
AB  - BACKGROUND: WBC depletion by filtration may prevent the transmission of HTLV-I,
      which requires cell-to-cell contact. The removal of HTLV-I-infected cells in
      routinely filtered blood cell components was measured. STUDY DESIGN AND METHODS:
      The study was conducted in Martinique where systematic screening for HTLV-I and 
      II and universal leukoreduction are mandatory. HTLV-I was quantified by use of
      real-time PCR in 8 RBC units and 4 PLT concentrates before and after filtration.
      HTLV-I proviral load in PBMNCs was determined in five of the eight HTLV-I
      infected blood donors. RESULTS: The amount of MNC-associated HTLV-I DNA in RBC
      units before filtration was 21 x 10(6)+/- 29 x 10(6) copies (mean +/- SD). HTLV-I
      was detected in 4 of 8 RBC units after filtration, with a number of copies in the
      MNC fraction ranging from 20 to 140, following a 4.9 to 5.8 log reduction. Flow
      cytometry analysis performed in 2 of the filtered RBC units containing detectable
      HTLV-I showed suboptimal and out-of-range leukoreduction (0.56 x 10(6) and 1.22 x
      10(6) residual WBCs). HTLV was not detected in filtered RBCs from the blood donor
      with the highest percentage of HTLV-I-infected PBMCs (9%). CONCLUSION: This study
      confirms that HTLV-I-infected cells can be detected in filtered blood cell
      components and shows that optimal leukoreduction is critical for HTLV-I removal.

PMID- 14692967
TI  - Decreased responsiveness and development of activation markers of PLTs stored in
      plasma.
AB  - BACKGROUND: Circulating PLTs have a low activation state and high responsiveness,
      which ensures adequate hemostatic activity at sites of vessel wall damage. PLTs
      collected for transfusion purposes preferably have retained these properties to
      restore impaired hemostasis with thrombocytopenia. STUDY DESIGN AND METHODS: We
      determined activation properties and coagulant activity of PLT-plasma
      preparations that were pooled or collected from single donors via apheresis.
      RESULTS: In comparison to freshly isolated PLTs, both apheresis and pooled PLTs
      exhibited slow exposure of CD62 upon storage, followed by surface appearance of
      procoagulant phosphatidylserine (PS) but not activated integrin alpha IIb beta 3.
      During storage, thrombin- and ADP-induced Ca2+ signal generation consistently
      decreased in apheresis and pooled PLTs, which was accompanied by lower agonist
      induced CD62 exposure and alpha IIb beta 3 activation. In flowing whole blood,
      stored apheresis PLTs showed lower collagen-induced Ca2+ responses and strikingly
      diminished participation in thrombus formation. Both apheresis and pooled PLT
      plasma concentrates exhibited high tissue factor-triggered thrombin generation,
      which was insensitive to PLT inhibition and attributable to PS-exposing
      microparticles. CONCLUSION: PLTs stored in plasma develop surface activation
      markers but, simultaneously, show markedly decreased responsiveness toward
      physiologic agonists. The plasma contains high coagulant activity, which is no
      longer PLT (activation)-dependent.

PMID- 14692968
TI  - Clinical evaluation of an HIV-1 and HCV assay and demonstration of significant
      reduction of the HCV detection window before seroconversion.
AB  - BACKGROUND: One HIV-1 and HCV assay simultaneously detects HIV-1 and HCV RNA
      (Procleix, Chiron Corp.). The main intended use of the assay is the testing of
      blood and blood products in blood banking. STUDY DESIGN AND METHODS: To evaluate
      the clinical sensitivity of the assay, 164 anti-HIV-1+ and 160 anti-HCV+ patients
      of different viral load were tested. The assay specificity was determined in 1000
      HIV-1- and HCV-seronegative blood donors. The ability of the assay to detect
      different HCV genotypes was investigated in a total of 40 patients of different
      genotypes (1-4). Furthermore, to investigate the reduction of the HCV window
      phase before seroconversion, serial samples of 25 hemodialysis patients who
      seroconverted to anti-HCV were also tested. RESULTS: The assay detected all 60
      HIV-1-infected patients with a viral load of greater than 50 copies per mL and 48
      of 104 patients with a viral load of less than 50 copies per mL. Moreover, all 60
      patients with an HCV RNA load of greater than 521 IU per mL and 7 of 100 patients
      with a viral load of less than 50 IU per mL tested positive. The assay
      specificity was found to be 100 percent. In addition, all 40 patients of
      different HCV genotypes were successfully detected. Finally, the median time that
      the assay detected HCV infection before second- and third-generation anti-HCV
      assay was found to be 183 and 91 days, respectively. CONCLUSION: The assay
      sensitivity and specificity, its ability to detect different HCV genotypes, and
      the significant reduction of window period of HCV infection further support its
      use for improving the safety of blood and blood products.

PMID- 14692969
TI  - Autoantibody formation after alloimmunization: are blood transfusions a risk
      factor for autoimmune hemolytic anemia?
AB  - BACKGROUND: The development of RBC autoantibodies resulting from or associated
      with allogeneic blood transfusions (i.e., RBC autoimmunization) is not a well
      recognized complication of RBC transfusions. STUDY DESIGN AND METHODS: T: he
      presentation, laboratory evaluation, clinical course, and management of two
      patients whose autoimmune hemolytic anemia followed allogeneic blood transfusion
      and occurred in association with the development of one or more alloantibodies is
      described. A retrospective analysis was performed of our blood-bank records over
      1 year to determine the frequency of RBC autoimmunization associated with
      alloimmunization. RESULTS: Out of 2618 patients who had a positive DAT or IAT,
      121 were identified with RBC autoantibodies; 41 of these patients had both allo-
      and autoantibodies to RBC antigens, whereas the remainder, 80, had only
      autoantibodies. At least 34 percent (12/41) of these patients (none with
      hemoglobinopathy) developed their autoantibodies in temporal association with
      alloimmunization after recent blood transfusion(s). CONCLUSION: RBC
      autoimmunization and the development of autoimmune hemolytic anemia should be
      recognized as a complication of allogeneic blood transfusion. The need for
      additional blood transfusion was successfully avoided in one patient by treatment
      with recombinant human EPO and corticosteroid therapy. Once RBC autoimmunization
      is identified, subsequent management should incorporate a strategy that minimizes
      subsequent exposure to allogeneic blood.

PMID- 14692970
TI  - Immune hemolytic anemia associated with teicoplanin.
AB  - BACKGROUND: Several drugs can cause immune hemolytic anemia. Here a patient who
      developed hemolytic anemia after treatment with teicoplanin is described. CASE
      REPORT: Owing to a two-vessel disease, a 68-year-old white man underwent coronary
      artery bypass grafting. He was readmitted for superficial sternal wound infection
      and sternal instability. Rewiring was required and worsening anemia characterized
      the course after the reoperation. Drugs used in the second admission were
      gentamycin, teicoplanin, paracetamol, and codeine. They were considered as a
      possible cause of drug-induced hemolytic anemia. RESULTS: The DAT was positive
      for complement and IgG. Autoanti-e was identified in the patient's undiluted
      serum sample. The eluate was reactive with all RBCs tested only after adding
      teicoplanin; when diluted 1:4, anti-e specificity was observed in the presence of
      teicoplanin. CONCLUSION: To our knowledge, this is the first report of immune
      hemolytic anemia owing to teicoplanin.

PMID- 14692971
TI  - CD177 polymorphisms: correlation between high-frequency single nucleotide
      polymorphisms and neutrophil surface protein expression.
AB  - BACKGROUND: Human neutrophil antigen-2a (NB1) is located on NB1 glycoprotein,
      which is expressed on subpopulations of neutrophils. PRV-1 is a gene that is over
      expressed in neutrophils from patients with polycythemia rubra vera. The gene
      encoding NB1 differs from PRV-1 at four nucleotides. The purpose of this study
      was to determine if PRV-1 and NB1 are alleles of the same gene or two separate
      genes; and, moreover, if they are alleles, to explore potential correlations to
      NB1 glycoprotein expression. STUDY DESIGN AND METHODS: Primer pairs were used to
      amplify WBC DNA in the regions surrounding the four NB1 polymorphic sites. The
      four resulting amplicons were sequenced. The size of the neutrophil population in
      each donor that stained brightly with CD177 antibody was assessed by flow
      cytometry. RESULTS: If PRV-1 and NB1 are separate genes, then all people should
      be heterozygous for the PRV-1/NB1 polymorphisms. Because 11 of 23 donors were
      homozygous for PRV-1 polymorphisms at all four sites, PRV-1 and NB1 are alleles
      of the same gene, CD177. When the sequenced exons were compared with PRV-1, 13
      single nucleotide polymorphisms (SNPs) that result in amino acid changes were
      found. The G42C NB1 polymorphism, found in 10 donors, was the most common SNP.
      The size of the CD177 bright-staining neutrophil population was greater in 42C/C
      donors than in 42G/G donors (66 +/- 20% vs. 41 +/- 21%, p = 0.004). CONCLUSIONS:
      PRV-1 and NB1 are alleles of the polymorphic gene CD177. The most common SNP in
      bp 42 predicted an amino acid change that may have an effect on protein
      expression.

PMID- 14692972
TI  - Characteristics of mutations at the D5S818 locus studied with a tightly linked
      marker.
AB  - BACKGROUND: Mutations to STR alleles are not well understood in terms of the
      mechanism(s) underlying such mutations or their relative frequency among
      different alleles at the locus. STUDY DESIGN AND METHODS: A cytosine/thymosine
      (C/T) polymorphism was discovered 13 nucleotides upstream from the 5'-end of the
      tandem array of the D5S818 locus (-13SNP). The -13SNP coincidentally creates a
      restriction site polymorphism for the restriction endonuclease SnaBI that is
      tightly linked to the tandem array of D5S818. Forty D5S818 addition/deletion
      mutations in the tandem array were characterized with RFLP analysis with SnaBI.
      RESULTS: Among 40 mutations studied, 34 (approximately 85%) were of paternal
      origin, 1 ( approximately 3%) was of maternal origin, and 5 (approximately 13%)
      had an unclear lineage of origin. In 26 cases where the magnitude of the repeat
      change could be determined, 23 (88%) involved changes of a single repeat unit,
      whereas 3 (12%) involved changes of 2 or more repeats. The number of additions to
      the tandem array was roughly equal to the number of deletions from the tandem
      array. In 19 instances it was possible to identify the parental allele that
      underwent the mutation. Alleles 13 and 14 were prone to mutation, whereas Allele
      11 was resistant. Thus, there is an unequal sensitivity to mutation among D5S818
      alleles. CONCLUSIONS: The use of the linked -13SNP marker has revealed several
      features of mutations at the D5S818 locus: 1) Single repeat changes are the most
      commonly observed. 2) Mutations are more likely in the paternal lineage. 3) Not
      all alleles undergo mutation with equal frequency.

PMID- 14692973
TI  - Clinical significance of nondiscriminated reactive results with the Chiron
      Procleix HIV-1 and HCV assay.
AB  - BACKGROUND: A NAT was developed (Procleix multiplex, Chiron Corporation) to
      simultaneously detect HIV-1 and HCV RNA with multiplex transcription-mediated
      amplification (mTMA) on pooled or single donations. HIV-1 and/or HCV RNA
      discriminatory probes confirm infection and discriminate the virus type. When a
      multiplex reactive sample does not react in discriminatory assays, the result is
      considered nondiscriminated reactive (NDR) and the donor status is uncertain.
      This study was designed to determine the clinical significance of NDR results.
      STUDY DESIGN AND METHODS: Three years of donor NAT and serology results were
      reviewed to determine HCV and HIV-1 infection rates as well as NDR events. Index
      NDR and seronegative donations were retested by mTMA and serology. Follow-up
      samples were tested by serology, mTMA, and PCR (selected samples). RESULTS: From
      April 1999 through April 2002, 5.1 million donations were screened with Procleix
      HIV-1 and HCV mTMA. The observed NDR rate declined from 0.014 percent (1 in 7242)
      to 0.0053 percent (1 in 18,795). None of the 462 donors with index NDR donations
      and additional NAT and serology data (from 724 donation and follow-up samples)
      were found infected. CONCLUSION: In most NDRs, the original mTMA reactivity is
      not reproducible and likely related to technical errors (mTMA cross
      contamination). The retest and clinical follow-up data, combined with published
      evidence that the two discriminatory assays have the same sensitivity as
      multiplex HIV-1 and HCV, support the recommendation that donors with an NDR
      result for whom the multiplex reactivity cannot be reproduced should either not
      be notified or be deferred or should be counseled that they are not infected and
      expeditiously reinstated.

PMID- 14692974
TI  - Quantitative real-time detection of parvovirus B19 DNA in plasma.
AB  - BACKGROUND: As of 2004, the European Pharmacopoeia demands that plasma pools for
      production of anti-D immunoglobulin should not contain more than 104 IU per mL of
      parvovirus B19 (B19V) DNA. Hence, before pooling, highly viremic donations have
      to be identified, and after pooling the level of B19V DNA must be determined. The
      performance of a new real-time B19V DNA PCR test (Roche, Mannheim, Germany) was
      studied, using a DNA extractor (NucliSens, bioMerieux, Boxtel, the Netherlands)
      for isolation of nucleic acid, and using a DNA quantification test (LightCycler
      apparatus, Roche, Mannheim, Germany) for amplification and detection. STUDY
      DESIGN AND METHODS: Dilutions of the international B19V DNA standard and
      reference preparations were tested to determine the precision, linear range, and
      accuracy of the assay and to calculate the factor for conversion of B19V DNA
      copies to IUs. The internal control signals, invalid test results, and the effect
      of cryo-poor plasma were studied as a measure for robustness. Routine performance
      was assessed by testing 164 manufacturing pools (not screened for B19V) and 1048
      test pools of 480 donations each. RESULTS: The copies-to-IU conversion factor was
      calculated to be 3.34 (95% CI, 3.07-3.63). The assay appears linear between 10(3)
      and 10(7) IU per mL. Between 10(3) and 10(5) IU per mL, the test can discriminate
      samples differing a factor two in B19V DNA content. Overall, 0.78 percent of the
      test results were invalid. Of 127 B19V DNA negative control plasma samples, 7
      were contaminated with low levels of B19V DNA. Of 164 nonscreened manufacturing
      plasma pools, 92 contained B19V DNA (56%); 13 contained more than 10(4) IU per
      mL. Of 503,040 donations, 29 contained more than 5 x 10(6) IU per mL B19V DNA
      (1:17,346). CONCLUSION: The B19V DNA quantification test (LightCycler, Roche ) is
      suitable for quantitative, routine, in-process measurement of B19V DNA levels in
      plasma pools, using the DNA extractor (NucliSens, bioMerieux) for nucleic acid
      isolation.

PMID- 14692975
TI  - Kinetics of G-CSF and CD34+ cell mobilization after once or twice daily
      stimulation with rHu granulocyte-stimulating factor (lenograstim) in healthy
      volunteers: an intraindividual crossover study.
AB  - BACKGROUND: G-CSF given as split dose increased the harvested number of CD34+
      cells in comparison to a once daily schedule, but the mechanism is poorly
      understood. STUDY DESIGN AND METHODS: To investigate the schedule dependency of G
      CSF in healthy volunteers with respect to CD34+ cell mobilization, the same dose
      of G-CSF was applied in four healthy volunteers in two different schedules (once
      daily vs. split doses twice daily) in a crossover design after a washout period
      of 3 months. CD34+ cell kinetics in serum were determined as well as G-CSF serum
      kinetics on Days 1 and 4 after stimulation. RESULTS: In all volunteers, the twice
      daily schedule led to a higher CD34+ cell count after 4 days of G-CSF stimulation
      (median, 94.5 vs. 47/ microL; p = 0.05). On Days 1 and 4, there was a higher peak
      serum concentration of G-CSF serum level after the once daily application (15,175
      vs. 6,859 pg/mL and 7440 vs. 2388 pg/mL, respectively) than after the twice daily
      schedule. In contrast, after the once daily application the minimum serum level
      of G-CSF serum level was lower than after the twice daily schedule (663 vs. 1361
      pg/mL and 246 vs. 441 pg/mL, respectively). No difference of area under the curve
      for G-CSF was observed on Days 1 and 4 after G-CSF stimulation. CONCLUSION: It is
      suggested that application of G-CSF twice daily leads to a higher CD34+ cell
      mobilization owing to a higher minimum serum level and therefore to a more
      continuous serum baseline level resulting in a more efficient CD34+ cell
      mobilization.

PMID- 14692976
TI  - Cord blood units collected at a remote site: a collaborative endeavor to collect
      umbilical cord blood through the Hawaii Cord Blood Bank and store the units at
      the Puget Sound Blood Center.
AB  - BACKGROUND: Umbilical cord blood is a useful source of hematopoietic stem cells,
      especially because compared to equivalent HLA-matched stem cells from unrelated
      adult donors. A network of community collection sites targeted at particular
      ethnic groups and serviced by a central processing and storage facility can
      maximize the genetic diversity of banked cord blood units (CBUs) in a cost
      effective fashion. STUDY DESIGN AND METHODS: The present study compared CBUs
      collected near the Puget Sound Blood Center in Seattle, WA, with those collected
      in Honolulu, HI, and processed in Seattle. Evaluated variables include collection
      volume, total nucleated cell count, cellular viability, CD34+ cell count,
      clonogenic activity, and donor race for a total of 1646 CBUs received from July
      1998 through November 2002. RESULTS: CBUs from the two sites did not differ with
      regard to volume or total nucleated cells. Those from Hawaii had significantly
      longer transit times (p < 0.001) and lower whole cord blood cell viability.
      However, the numbers of CFU and viable CD34+ cells were not affected by remote
      collection. CBUs screened from Seattle were largely from Caucasian donors,
      whereas over 85 percent of those from Honolulu were from donors of Asian-Pacific
      Islander or mixed ethnicity. CONCLUSION: These studies demonstrate the
      feasibility of long-distance umbilical cord blood banking. Arrangements such as
      those described here could be used to help target cost-effective collection from
      minority populations and increase the HLA and ethnic diversity for CBUs.

PMID- 14692977
TI  - A comparison of PLT collections from two apheresis devices.
AB  - BACKGROUND: The aim of this study was to compare two apheresis devices (COBE
      Trima and COBE Spectra, Gambro BCT). STUDY DESIGN AND METHODS: The study compares
      103 Trima procedures with 61 Spectra procedures. The comparison of single-donor
      PLTs (SDPs) separation parameters and anticoagulant infusion to the donors were
      the primary targets. Yield and residual amounts of WBCs of SDPs were secondary
      targets. Residual amounts of WBCs were measured with the Nageotte method.
      RESULTS: Trima and Spectra groups were comparable before apheresis. Two
      procedures were terminated before completion in the Trima group owing to vein
      damage. Trima infused more anticoagulant--352 +/- 104 mL versus 297 +/- 75 mL (p
      < 0.01)--and was quicker than Spectra. The time to obtain 3.5 x 10(11) was
      (median) 55.8 minutes for the Trima machine and 80.3 minutes for Spectra machine
      (p < 0.001). Regarding leukoreduction, all the SDPs had fewer than 1 x 10(6) WBCs
      per unit except for one in product obtained by the Trima machine. CONCLUSIONS:
      The Trima machine is faster and more efficient than the Spectra machine, and both
      machines allow standard leukoreduced SDPs to be obtained. Although donors receive
      a higher anticoagulant infusion with the Trima machine, their tolerance is
      acceptable.

PMID- 14692978
TI  - Platelet activation during plasma-reduced multicomponent PLT collection: a
      comparison between COBE Trima and Spectra LRS turbo cell separators.
AB  - BACKGROUND: The wide diffusion of multicomponent collection in donor apheresis
      has led to the yielding of different components, such as plasma-reduced platelet
      pheresis at high PLT concentration. We investigated whether this collection
      modality could induce more PLT activation compared to standard plateletpheresis.
      STUDY DESIGN AND METHODS: Forty-one plateletpheresis collections (20 Trima and 21
      Spectra LRS Turbo v.7.0, COBE) were evaluated. Donor, procedure, and product data
      were recorded. ADP, collagen, and U46619 (a thromboxane-A2 analog)-induced PLT
      aggregation was investigated in basal (donor) and final (plateletpheresis unit)
      samples. The expression of PLT activation marker P-selectin (CD62P) was studied
      using flow cytometry in basal and final samples. In all cases, P-selectin was
      investigated in final samples after stimulation with ADP to assess for a possible
      further release of the antigen. Four additional plateletpheresis procedures were
      performed in donors from Group A, using the traditional, nonplasma-reduced
      program. RESULTS: Plateletpheresis obtained by means of the Trima device showed a
      lower response to in-vitro induced PLT aggregation and a higher percentage of P
      selectin-expressing PLT when compared to products obtained using the Spectra
      device. Moreover, P-selectin release after ADP stimulation was reduced in
      plateletpheresis units obtained using the Trima device. These differences
      disappeared when a nonplasma-reduced collection program was used. In-vivo
      evaluation did not detect any difference between plateletpheresis obtained by
      means of the two cell separators. CONCLUSIONS: Plateletpheresis units obtained by
      means of multicomponent collection show a higher degree of PLT activation
      compared to traditional plateletpheresis procedures when high-concentration
      plasma-reduced products are collected. Randomized clinical studies are needed to
      assess the real impact of these findings in terms of in-vivo efficacy of plasma
      reduced plateletpheresis units.

PMID- 14692979
TI  - Radiolabeling of PLTs to assess viability: a proposal for a standard.

PMID- 14692980
TI  - Problems of prenatal parentage analyses.

PMID- 14692981
TI  - Adverse effects in blood donors after whole-blood donation: you find what you
      look for!

PMID- 14692982
TI  - Molecular basis for p blood group phenotype in China.

PMID- 14692984
TI  - Getting your feet wet: becoming a public health nurse, part 1.
AB  - While the competencies and theory relevant to public health nursing (PHN)
      practice continue to be described, much less attention has been given to the
      knowledge derived from practice (clinical know-how) and the development of PHN
      expertise. A study was designed to address this gap by recruiting nurses with
      varied levels of experience and from various practice sites. A convenience sample
      of 28 public health nurses and seven administrators/supervisors were interviewed.
      A subsample, comprised of less-experienced public health nurses, were followed
      longitudinally over an 18-month period. Data included more than 130 clinical
      episodes and approximately 900 pages of transcripts and field notes. A series of
      interpretive sessions focused on identifying salient aspects of the text and
      comparing and contrasting what showed up as compelling, puzzling, and meaningful
      in public health nurses' descriptions. This interpretive analysis revealed
      changes in understanding of practice and captured the development of clinical
      know-how. In Part 1, we describe the sample, study design, and two aspects of
      clinical knowledge development--grappling with the unfamiliar and learning
      relational skills--that surfaced in nurses' descriptions of early clinical
      practice. In Part 2, which is to be published in the next issue of Public Health
      Nursing (SmithBattle, Diekemper, & Leander, 2004), we explore gradual shifts in
      public health nurses' understanding of practice that led to their engagement in
      upstream, population-focused activities. Implications of these findings for
      supporting the clinical learning of public health nurses and the development of
      expertise are described.

PMID- 14692985
TI  - Factors influencing homelessness in women.
AB  - The specific aims of the article were to: (i) compare childhood experiences of
      intimacy and autonomy as they occurred in the families of origin of women who
      have and women who have not experienced homelessness; (ii) compare social
      support, reciprocity, and conflict as they occurred in the childhood support
      networks and in the current support networks of women who have and women who have
      not experienced homelessness; (iii) examine the relationships between intimacy
      and autonomy in families of origin and the social support networks from childhood
      of women who have and women who have not experienced homelessness. Descriptive
      correlational design: 255 women were interviewed to determine levels of intimacy,
      autonomy, social support, reciprocity, and conflict in childhood relationships.
      The ANCOVA models for each of support, reciprocity, and conflict indicated a
      significant group effect. The post-hoc analysis for support indicated that the
      homeless group was significantly lower in support and reciprocity and
      significantly higher in conflict than the never-homeless groups. The never
      homeless, never-abused group scored significantly higher on autonomy and intimacy
      than the homeless or the never-homeless, abused groups. This study demonstrates
      the significance of families of origin and learning how to develop and utilize
      support systems in preventing or reducing homelessness.

PMID- 14692986
TI  - Informal caregiving burden: an overlooked aspect of the lives and health of women
      transitioning from welfare to employment?
AB  - Informal caregiving occurs among communities in all socioeconomic strata and is
      largely provided by women. Although an extensive amount of research focusing on
      caregiver burden has been conducted within nursing, little is known about
      informal caregiving among low-income women, particularly within the context of
      welfare reform. This study examined the extent of informal caregiver burden in
      low-income women transitioning off welfare and the relationship between informal
      caregiving and maintaining employment. A random sample of 32 adults who had
      recently received welfare was obtained (n = 31 women), although there was
      significant difficulty locating potential subjects. Sixty-three percent of
      participants were providing nonparental forms of informal caregiving. Caregiver
      burden scores among this group were highest in the time-dependence dimension of
      caregiving. Over 30% of participants reported having to leave a job within the
      past year because of their caregiving responsibilities. These findings suggest
      that the informal caregiving responsibilities of low-income women may be an
      overlooked aspect of welfare reform policy. Given the emphasis on case management
      and policy advocacy in their roles, public health nurses are uniquely positioned
      to partner with local welfare-to-work organizations, educate program staff, and
      further develop existing assessment processes to better address caregiving
      responsibilities within low-income families.

PMID- 14692987
TI  - Essential concepts in developing community-university partnerships. CareLink: the
      Partners in Caring Model.
AB  - University and community partnerships are being created to increase community
      based educational experiences for nursing students and to assist agencies in
      facing ever-decreasing resources to pay for health services for clients. Many
      challenges often burden these partnerships, leading to a less than satisfying
      experience for all those involved. The Partners in Caring Model described in this
      article is one approach to forming a successful partnership, proven effective in
      meeting the educational needs of the University of Connecticut, School of Nursing
      students, while providing additional resources to the Visiting Nurse Association
      of Central Connecticut, Inc. Using Anderson and McFarlane's Community as Partner
      Model as the framework, the essential principles behind the development of this
      successful partnership are discussed. The Partners in Caring Model demonstrates
      that community-university partnerships can sustain themselves when the partners
      have a commitment to care for the population being served, and it is a shared
      responsibility between education and practice.

PMID- 14692988
TI  - Predictors of home health care services for cerebral vascular disease patients in
      Taiwan.
AB  - The National Health Insurance in Taiwan has rigid regulations for reimbursing
      home nursing care with payment only for technical/skill care such as changing
      nasogastric tubes, urine catheters, and tracheal tubes, wound care, and specimen
      collection. Patients with chronic illnesses who reside at home, however, require
      care that is holistic and focuses on wellness rather than illness. Cerebral
      vascular disease (CVD) patients are the largest group receiving home nursing
      care. They qualify for reimbursement under NHI. The purposes of this study were
      to quantify the home health care (HHC) needs of CVD patients and to understand
      predictors for HHC services for CVD patients in Taiwan. A descriptive correlation
      design was used to examine the relationship between a CVD patient's health status
      and the need for HHC services. In total, 195 patients were interviewed by one
      trained research assistant, with 124 patients being from Taipei (an urban area in
      Taiwan) and the remaining 71 from I-lan (a rural area in Taiwan). The mean age of
      subjects was 74.8 years, with 60% of the sample being female. Physiological
      health status scores (M = 2.56, SD = 0.58, range = 1-5) were worse than the
      psychosocial health status scores (M = 2.37, SD = 0.91, range = 1-5), which
      indicates that the need for health education and skilled nursing services was
      higher than referral services for professional HHC services. Results suggest that
      there is a need to develop and shape NHI policy to cover more holistic HHC
      services for CVD patients.

PMID- 14692989
TI  - The efficacy of a home-based nursing program in diabetic control of elderly
      people with diabetes mellitus living alone.
AB  - The purpose of this study was to evaluate the efficacy of a home-based nursing
      program in the diabetic control of elderly people with diabetes mellitus living
      alone. Patients meeting the sampling criteria were recruited from a medical
      center and 10 health centers in Taipei for this quasi-experimental study. By
      matching the effects of age, sex, education, and history of diabetes, subjects
      were assigned semirandomly to two groups based on the intensity of home-based
      nursing care visitations. Group I was defined as daily visits to supervise diet,
      exercise, medication, and self-monitoring blood sugar (n = 15) and Group II as
      weekly visits to supervise diet, exercise, medication education, and self
      monitoring blood sugar (n = 15). Patients who agreed only to receive blood
      examination were assigned to the control group (n = 14). The results of the study
      showed that reductions in fasting blood sugar, postmeal blood sugar, and
      hemoglobin A1c (HbA1c) in Groups I and II were significantly greater than those
      in the control group. The reduction in the total cholesterol and low-density
      lipoprotein in Groups I and II was significantly greater than that in the control
      group. There were no significant differences among the three groups in the
      improvement of high-density lipoprotein (HDL) and triglycerides (TGs). Group I
      revealed a significantly greater weight reduction compared to Group II. There was
      no significant difference between Groups I and II in the improvements of diabetes
      knowledge, depression level, or quality of life. From the research findings,
      based on cost-effectiveness, it is recommend that Program II be implemented.

PMID- 14692990
TI  - Public health education and practice using geographic information system
      technology.
AB  - The use of geographic information system (GIS) technology allows public health
      practitioners to explore disparities in health, analyze disease outbreaks, and
      prioritize the use of limited resources for improving population health. Nursing
      students benefit from use of World Wide Web GIS resources as they develop
      knowledge and skill in assessing population health and planning interventions.
      This article identifies the benefits of GIS for public health practitioners,
      presents a communicable disease control application of GIS, and discusses a GIS
      module used in an undergraduate nursing education course. Uniform standards for
      making health data available for public use with GIS are discussed.

PMID- 14692991
TI  - Knowledge and attitudes of nurses working in sexual health clinics in the United
      Kingdom toward post-sexual exposure prophylaxis for HIV infection.
AB  - The use of anti-human immunodeficiency virus (HIV) drugs after occupational
      exposure to HIV is a proven method of preventing some HIV infections. There is
      anecdotal evidence that this treatment is being used to treat recently exposed
      sexual contacts of HIV infection, known as non-occupational post-exposure
      prophylaxis (NONOPEP). This raises the issues of the impact of such treatment on
      sexual behavior and public health. Six hundred questionnaires were distributed to
      nurses working in sexual health clinics. Four hundred and six (67%) were
      returned. Questionnaires contained items related to awareness of HIV NONOPEP and
      items included attitudes related to its use. Seventy two percent of respondents
      were aware of HIV NONOPEP, and 17% had experience of its use in their clinic.
      Twenty one percent of respondents indicated that their clinic had a specific HIV
      NONOPEP policy. In relation to attitudes, practitioners were more positive of
      NONOPEP in relation to an HIV exposure within a long-term relationship than
      exposure within a casual relationship, indicating that the mode of HIV exposure
      was a factor in the justification of NONOPEP. Practitioners seemed to support the
      notion that HIV NONOPEP use in a casual exposure may increase the likelihood of
      unsafe sexual practice; however, practitioners with experience were less likely
      to express this view. It is suggested that an informed debate and NONOPEP policy
      development within all sexual health clinics will militate against judgmental
      views affecting access and care.

PMID- 14692992
TI  - The Interaction Model of Client Health Behavior as a conceptual guide in the
      explanation of children's health behaviors.
AB  - This study used the Interaction Model of Client Health Behavior (IMCHB) as a
      conceptual guide to explain the correlates of children's diet and physical
      activity and explore the relationships of sex with their diet and physical
      activity of the school-aged child. A descriptive correlational study was
      conducted on 371 fifth-grade students and their parents. Information on the
      family's demographics, health experience, social influence, and environmental
      resources was collected, as well as data on the children's intrinsic motivation,
      cognitive appraisal, and affective response to food/physical activity. Children's
      self-reports on diet and physical activity were collected, as were parents' self
      reports on health habits. Food preferences and diet self-efficacy explained the
      most variance in diet behavior for girls and boys. Girls scored healthier on food
      preferences and diet self-efficacy than did boys, but no difference was detected
      in their diet behavior. Girls participated in more low-intensity physical
      activity, but boys participated in more high-intensity physical activity than did
      girls. Findings provide strong support for the use of the IMCHB to explain
      children's diet but weak support for the explanation of children's physical
      activity. Further study of additional factors predictive of physical activity is
      indicated.

PMID- 14692993
TI  - A comparison of health practices of Canadian and Jordanian nursing students.
AB  - The purpose of this study was to compare health-promoting practices of Canadian
      (n = 49) and Jordanian (n = 44) first-year nursing students using the revised
      Health-Promoting Lifestyle Profile II. Results indicated significant differences
      between the groups on three subscales: health responsibility, physical activity,
      and interpersonal relations; however, both groups had similarly low scores.
      Implications for nurse educators are discussed from both curricular and cross
      cultural perspective that focuses on health-promotion activities and programs.

PMID- 14692995
TI  - Early neural activity in Necker-cube reversal: evidence for low-level processing
      of a gestalt phenomenon.
AB  - Normally we experience the visual world as stable. Ambiguous figures provide a
      fascinating exception: On prolonged inspection, the "Necker cube" undergoes a
      sudden, unavoidable reversal of its perceived front-back orientation. What
      happens in the brain when spontaneously switching between these equally likely
      interpretations? Does neural processing differ between an endogenously perceived
      reversal of a physically unchanged ambiguous stimulus and an exogenously caused
      reversal of an unambiguous stimulus? A refined EEG paradigm to measure such
      endogenous events uncovered an early electrophysiological correlate of this
      spontaneous reversal, a negativity beginning at 160 ms. Comparing across nine
      electrode locations suggests that this component originates in early visual
      areas. An EEG component of similar shape and scalp distribution, but 50 ms
      earlier, was evoked by an external reversal of unambiguous figures. Perceptual
      disambiguation seems to be accomplished by the same structures that represent
      objects per se, and to occur early in the visual stream. This suggests that low
      level mechanisms play a crucial role in resolving perceptual ambiguity.

PMID- 14692996
TI  - ERP components associated with successful and unsuccessful stopping in a stop
      signal task.
AB  - The primary aim of this study was to examine how response inhibition is reflected
      in components of the event-related potential (ERP), using the stop-signal
      paradigm as a tool to manipulate response inhibition processes. Stop signals
      elicited a sequence of N2/P3 components that partly overlapped with ERP
      components elicited by the reaction stimulus. N2/P3 components were more
      pronounced on stop-signal trials than on no-stop-signal trials. At Cz, the stop
      signal P3 peaked earlier on successful than on unsuccessful stop trials. This
      finding extends the horse race model by demonstrating that the internal response
      to the stop signal (as reflected in stop-signal P3) is not constant, but
      terminates at different moments in time on successful and unsuccessful stop
      trials. In addition, topographical distributions and dipole analysis of high
      density EEG recordings indicated that different cortical generators were involved
      in P3s elicited on successful and unsuccessful stop-signal trials. The latter
      results suggest that P3 on successful stop-signal trials not only reflects stop
      signal processing per se, but also efficiency of inhibitory control.

PMID- 14692997
TI  - The sequential processing of visual feature conjunction mismatches in the human
      brain.
AB  - To clarify the brain mechanism for multifeature stimulus comparison, subjects
      matched the features of two serial visual stimuli in pairs. Stimulus pairs were
      of four categories: C-S-, color same, shape same (match); C-S+, color same, shape
      different (shape mismatch); C+S-, color different, shape same (color mismatch);
      C+S+, color different, shape different (conjunction mismatches). Subjects matched
      the stimuli in three different sessions according to different attention tasks:
      attending to color (Ac), attending to shape (As), or attending to both color and
      shape (Acs). A negative one-peak brain potential, N270, was elicited in all the
      mismatch conditions with amplitude enhanced in the task-relevant mismatch.
      Negative potential with two peaks, N270 and N400, appeared when attending to the
      conjunction mismatches concurrently. The two serial negativities in response to
      attended feature conjunctions might reflect the temporal different stages for
      processing conjunction mismatches or conflicts.

PMID- 14692998
TI  - Effects of auditory distraction on electrophysiological brain activity and
      performance in children aged 8-13 years.
AB  - Distractibility was investigated in three age groups of children (8-9, 10-11, and
      12-13 years) with event-related brain potentials (ERPs) and performance measures
      in a forced-choice visual task. Distraction was reflected by increased reaction
      times (RTs) and decreased performance accuracy in the visual discrimination task
      following presentation of unexpected novel sounds. The amplitude of the late
      portion of the P3a elicited by novel sounds was largest for the youngest group
      and showed a centrally dominant scalp distribution and smallest for the oldest
      group with a frontal scalp distribution. A frontally dominant late negativity
      (LN) that was largest in the youngest group followed the P3a. Correlation between
      the RT increase caused by the distracting novel sounds and the amplitude of the
      LN elicited by these sounds suggested that the LN is associated with the degree
      of attention engaged by the distracting sounds.

PMID- 14692999
TI  - BIS-BAS sensitivity and cardiac autonomic stress profiles.
AB  - This study examined the relationship of sensitivities of Gray's behavioral
      inhibition system (BIS) and behavioral approach system (BAS) to cardiac autonomic
      stress responses during laboratory tasks among 65 healthy men (n=34) and women
      (n=31) aged 22-37 years. Carver and White's BIS-BAS scales were used to measure
      BIS and BAS sensitivities. We measured heart rate (HR), respiratory sinus
      arrhythmia, and preejection period during mental arithmetic, a reaction time
      task, and a speech task. Results revealed that BAS sensitivity was related to HR
      reactivity and parasympathetic withdrawal during the tasks, but was unrelated to
      baseline levels. BIS sensitivity was unrelated to both reactivity and baseline
      levels of all measures. Overall, our results suggest that the relationship of the
      BAS with cardiac reactivity seems to be mediated by the parasympathetic nervous
      system.

PMID- 14693000
TI  - Comparing arithmetic and semantic fact retrieval: effects of problem size and
      sentence constraint on event-related brain potentials.
AB  - Event-related potentials were recorded with 61 electrodes from 16 students who
      verified either the correctness of single-digit multiplication problems or the
      semantic congruency of sentences. Multiplication problems varied in size and
      sentence fragments in constraint. Both semantic and arithmetic incongruencies
      evoked a typical N400 with a clear parieto-central maximum. In addition,
      numerically larger problems (8x7), in comparison to smaller problems (3x2),
      evoked a negativity starting at about 360 ms whose maximum was located over the
      right temporal-parietal scalp. These results indicate that the arithmetic
      incongruency and the problem-size effect are functionally distinct. It is
      suggested that the arithmetic and the semantic incongruency effects are both
      functionally related to a context-dependent spread of activation in specialized
      associative networks, whereas the arithmetic problem-size effect is due to
      rechecking routines that go beyond basic fact retrieval.

PMID- 14693001
TI  - Repetition and semantic priming of nonwords: implications for theories of N400
      and word recognition.
AB  - ERPs were elicited by two types of orthographically legal, pronounceable
      nonwords. One nonword set was derived from and resembled real words, whereas the
      other set did not. Nonwords derived from related root words elicited N400
      semantic priming effects similar to those obtained for words, indicating semantic
      activation of the root words. N400 repetition priming effects from nonderived
      nonwords were similar to those obtained for words. The elicitation of N400 by
      only derived nonwords would have suggested it was generated by the activation of
      word meanings, per se. However, both types of nonwords produced an N400, and an
      N400 priming effect. Because nonderived nonwords are not associated with meaning,
      the N400 cannot be generated by semantic activation per se. Rather, the N400
      appears to be generated by orthographic/phonological analysis and is attenuated
      by the top-down feed of semantic information to the orthographic/phonological
      level.

PMID- 14693002
TI  - Respiratory sinus arrhythmia as an index of emotional response in young adults.
AB  - The relationship between respiratory sinus arrhythmia (RSA) and valence and
      arousal remains unclear. In the present study, the associations between emotion
      responses and tonic or task-related changes in RSA were assessed. Specifically,
      the sensitivities of changes in interbeat interval, RSA, and skin conductance to
      the valence and arousal values of emotional stimuli were examined. This study
      also explored the association between tonic RSA and subjective, expressive, and
      physiological emotional responses. Response measures were collected from 56
      adults during baseline and film-viewing periods. Tonic RSA was not significantly
      related to any of the response measures. Increased skin conductance and decreased
      RSA were associated with arousal independent of valence. Interbeat interval was
      related to affective valence and not arousal. These findings suggest that RSA may
      be a useful adjunct to skin conductance measures in assessing emotional arousal.

PMID- 14693003
TI  - The error-related negativity as a state and trait measure: motivation,
      personality, and ERPs in response to errors.
AB  - This study examines changes in the error-related negativity (ERN/Ne) related to
      motivational incentives and personality traits. ERPs were gathered while adults
      completed a four-choice letter task during four motivational conditions. Monetary
      incentives for finger and hand accuracy were altered across motivation conditions
      to either be equal or favor one type of accuracy over the other in a 3:1 ratio.
      Larger ERN/Ne amplitudes were predicted with increased incentives, with
      personality moderating this effect. Results were as expected: Individuals higher
      on conscientiousness displayed smaller motivation-related changes in the ERN/Ne.
      Similarly, those low on neuroticism had smaller effects, with the effect of
      Conscientiousness absent after accounting for Neuroticism. These results
      emphasize an emotional/evaluative function for the ERN/Ne, and suggest that the
      ability to selectively invest in error monitoring is moderated by underlying
      personality.

PMID- 14693004
TI  - Effects of cycling exercise on the soleus H-reflex and state anxiety among men
      with low or high trait anxiety.
AB  - The present study examined the effects of low- and high-intensity cycling
      exercise on the H-reflex and state anxiety among men having low (n=20) or high
      (n=20) trait anxiety. Participants completed measures of state anxiety and
      underwent elicitation and recording of the H-reflex in the soleus muscle before
      and 10 min after three 20-min conditions: (1) quiet rest, (2) cycling at 40%
      VO2peak, and (3) cycling at 70% VO2peak. We found that (1) exercise, but not
      quiet rest, resulted in a reduction of the H-reflex; the magnitude of the
      reduction did not differ between men having low or high trait anxiety; (2)
      exercise and quiet rest resulted in similar reductions of state anxiety, and the
      magnitude of the reductions was larger for men having high trait anxiety than low
      trait anxiety; and (3) reductions of the H-reflex were unrelated to reductions of
      self-reported state anxiety across all three conditions. Contrary to prior
      opinion, the postexercise reduction in the H-reflex reported by previous
      researchers and in the present study appears to be unrelated to self-reported
      anxiety after exercise.

PMID- 14693005
TI  - Word-specific cortical activity as revealed by the mismatch negativity.
AB  - Neurophysiological brain activity evoked by individual spoken words and
      pseudowords was recorded and the mismatch negativity (MMN), an automatic index of
      experience-dependent auditory memory traces, was calculated. Consistent with
      earlier reported results, the MMN response to word-final syllables was enhanced
      compared with that elicited by the same syllables placed in a pseudoword context.
      Here we now demonstrate that the enhancement of the MMN elicited by two
      individual words showed different scalp topographies. The early word-specific
      brain activity is consistent with the assumption that the memory traces activated
      by individual words are carried by large neuronal ensembles that differ in their
      distributions over the cortex. Current source estimates localized the between
      word differences in the right hemisphere and in parieto-occipital left
      hemispheric areas. The differential brain responses to individual words appeared
      as early as approximately 100 ms after the recognition points of the words,
      suggesting that their specific memory traces become active almost immediately
      after the information in the acoustic input is sufficient for word
      identification.

PMID- 14693006
TI  - On-line executive control: an electromyographic study.
AB  - In a choice reaction time (RT) task, electromyographic (EMG) recordings allowed
      us to fractionate RT into two subcomponents, namely premotor time and motor time.
      This has been done for correct trials and errors. The analysis of the EMG burst
      and motor time (between EMG onset and overt response) showed that the EMG burst
      amplitude was reduced and the motor time was longer for errors than for correct
      responses. In the same way as posterror slowing on the RT was interpreted as
      revealing between-trials changes in executive control, the present data provide
      direct evidence for an on-line, within-trial, executive control.

PMID- 14693007
TI  - ERP indices of emotionality and semantic cohesiveness during recognition
      judgments.
AB  - Event-related potentials (ERPs) were used to examine the impact of emotionality
      on false recognition. In Experiment 1, participants discriminated previously
      studied words from neutral and negatively valenced emotional foils. Emotional
      words elicited a more positive ERP than did neutral words and emotional foils
      were falsely recognized more often than neutral foils. In Experiment 2, the
      hypothesis that emotionality-based false recognition is due to the semantic
      cohesiveness of emotional words was tested by including a highly associated but
      emotionally neutral category (animals). It was emotional and not animal foils
      that elicited greater positivity in the ERP and increased false positive
      response. These data provide little support for semantic cohesiveness as the
      basis for false recognition effects, but are consistent with the view that the
      salience of emotional words can be falsely attributed to familiarity in the
      context of a recognition task.

PMID- 14693008
TI  - Event-related potentials associated with sound discrimination versus novelty
      detection in children.
AB  - In children, deviant sounds in an oddball paradigm elicit a mismatch negativity
      (MMN) indexing discrimination of sound change and late difference negativity
      (LDN) with unknown functional significance. Salient sounds elicit an ERP index if
      orienting, P3a, and a late negative component, Nc. We compared children's
      responses elicited by moderate sound changes and novel sounds to examine the
      relationships between MMN and LDN, and LDN and Nc. Two components of the Nc, the
      Nc1 and Nc2, were identified. The scalp topography of LDN differed from those of
      the MMN and Nc1. Children's early P3a appeared mature but late P3a lacked frontal
      predominance. The findings suggested that LDN is not linked with either the
      sensory or attentional processing. It might reflect cognitive, albeit
      preattentive, processing of sound change. The Nc1 appears to reflect cognitive
      attentive processing of salient stimuli and the Nc2 might reflect reorienting
      after distraction.

PMID- 14693009
TI  - Randomization tests for ERP topographies and whole spatiotemporal data matrices.
AB  - In ERP studies, the comparison of topographies (multichannel measurements) or
      whole spatiotemporal data matrices (multichannel time series of measurements),
      the classical statistical tests very often cannot be used. It is argued that, for
      these comparisons, randomization tests are an excellent alternative. It is also
      argued that the randomization test is superior to another resampling method, the
      bootstrap, because exact probability statements (e.g., p values) can be made. A
      review is given of the literature on randomization tests designed for
      electrophysiological data. New randomization tests are presented and applied to
      two data sets, one coming from a psychopharmacological experiment and the other
      from an ERP experiment in visual word recognition.

PMID- 14693010
TI  - Changes in rolandic mu rhythm during observation of a precision grip.
AB  - We recorded 128-channel EEG from 16 participants while they observed, imitated,
      and self-initiated the precision grip of a manipulandum. Mu rhythm amplitudes
      were significantly lower during observation of a precision grip than during
      observation of a simple hand extension without object interaction. Scalp
      topographies for subtractions of observation, imitation, and execution conditions
      from the control condition showed a high degree of congruence, supporting the
      notion of a human observation-execution matching system. Surface Laplacian
      transformations suggest that the decrease in mu amplitude during precision grip
      observation reflects desynchronization of mu rhythm generators in the
      sensorimotor cortex. These results support the hypothesis that sensorimotor
      cortex is a neural substrate involved in the representation of both self- and
      other-generated actions and show the mu rhythm is sensitive to subtle changes in
      observed motor behavior.

PMID- 14693011
TI  - Stimulus modality, perceptual overlap, and the go/no-go N2.
AB  - Stimuli that elicit a prepotent but incorrect response are typically associated
      with an enhanced electrophysiological N2 that is thought to index the operation
      of a control process such as inhibition or conflict detection. However, recent
      studies reporting the absence of the N2 modulation in go/no-go tasks involving
      auditory stimuli challenge this view: It is not clear why inhibition or conflict
      detection should be sensitive to the modality of the stimulus. Here we present
      electrophysiological data from a go/no-go task suggesting that the relative size
      of the N2 modulation in visual and auditory tasks depends on the perceptual
      overlap between the go and no-go stimuli. Stimuli that looked similar but sounded
      different were associated with a typical visual N2 modulation and the absence of
      an auditory N2 modulation, consistent with previous findings. However, when we
      increased the perceptual overlap between the auditory stimuli, a large no-go N2
      was observed. These findings are discussed in terms of existing hypotheses of the
      N2, and clarify why previous studies have not found an N2 modulation in auditory
      go/no-go tasks.

PMID- 14693013
TI  - Pellagra: dermatitis, dementia, and diarrhea.
AB  - Pellagra defines systemic disease as resulting from a marked cellular deficiency
      of niacin. It is characterized by 4 "D's": diarrhea, dermatitis, dementia, and
      death. Diagnosis of pellagra is difficult in the absence of the skin lesions, and
      is often facilitated by the presence of characteristic ones. The dermatitis
      begins as an erythema. Acute pellagra resembles sunburn in its first stages, but
      tanning occurs more slowly than typically in sunburn. Exacerbation follows re
      exposure to sunlight. In this work we review the findings of this once mysterious
      disorder, one that still challenges clinicians world-wide.

PMID- 14693012
TI  - Awareness of sleepiness when driving.
AB  - The extent to which sleepy drivers are aware of sleepiness has implications for
      the prevention of sleep-related crashes, especially for drivers younger than 30
      years old who are most at risk. Using a real car interactive simulator, we report
      on EEG, subjective sleepiness, and lane drifting (sleepiness-related driving
      impairment) from 38 sleep-restricted, healthy young adults undergoing
      nontreatment control conditions from three (unpublished) investigations using the
      same experimental protocols for assessing various drinks intended to alleviate
      sleepiness. Participants drove 2 h during midafternoon under monotonous
      conditions. For all studies, subjective sleepiness and EEG activity indicative of
      sleepiness were highly correlated, with both changing concomitantly, along with
      lane drifting. Drivers had knowledge of their physiological sleepiness. There
      were indications that sugar content of these drinks may additionally affect
      sleepiness.

PMID- 14693014
TI  - Seasonal variation of dermatologic disease in the USA: a study of office visits
      from 1990 to 1998.
AB  - BACKGROUND: Seasonal variation has been demonstrated in many diseases, including
      certain skin diseases. OBJECTIVE: To determine whether there is seasonal
      variation in dermatologic office visits in the USA. METHODS: Data on dermatologic
      office visits were obtained from representative visits to outpatient physicians
      in the USA from the National Ambulatory Medical Care Survey from 1990 to 1998.
      Office visit seasonality was examined for all skin conditions, and individually
      for the 15 most commonly diagnosed conditions. RESULTS: Office visits for skin
      conditions were seasonal (P = 0.002). The magnitude of variation can be roughly
      expressed by the following scheme: actinic keratosis (P = 0.0001) > acne (P =
      0.0001) > folliculitis (P = 0.002) > dyschromia (P = 0.01) > seborrheic keratosis
      (P = 0.04) > psoriasis (P = 0.07) > seborrheic dermatitis (P = 0.09). Visits for
      skin cancer, not otherwise specified (skin cancer NOS), atopic dermatitis, cysts,
      common wart, wart, not otherwise specified (wart NOS), rosacea, contact
      dermatitis, and benign tumors showed no significant seasonal variations or
      trends. CONCLUSIONS: Dermatologic office visits are seasonal, with visits for
      individual diseases varying in their magnitude of seasonality. This seasonal
      variation may be a result of biological and nonbiological variables.

PMID- 14693015
TI  - Necrolytic migratory erythema: clinicopathologic study of 13 cases.
AB  - BACKGROUND: The clinical mucocutaneous manifestations of glucagonoma syndrome are
      recognized easily when they occur in the classic pattern of acral or
      periorificial lesions evolving in recurrent crops, with an annular and migratory
      distribution, in a patient with diabetes mellitus who has had recent weight loss
      and anemia. Not infrequently, noncharacteristic clinical and histopathologic
      features are observed and, in these cases, the diagnosis of pancreatic neoplasm
      may be delayed. AIM: To review the clinical and histopathologic features of
      cutaneous manifestations of glucagonoma syndrome. METHODS: The clinicopathologic
      features of 13 patients (eight women) with widespread or localized cutaneous
      eruption as a manifestation of islet cell pancreatic carcinoma with marked
      glucagon secretion (glucagonoma) were reviewed. RESULTS: The definitive diagnosis
      of the cutaneous eruption was established at the time of diagnosis of the
      pancreatic neoplasm (three patients) or afterwards (10 patients). In nine
      patients, the mucocutaneous manifestations preceded the diagnosis of the
      pancreatic neoplasm by 1 month to 3 years (mean, 12 months). In only eight biopsy
      specimens were the histopathologic features considered to be suggestive or
      characteristic of necrolytic migratory erythema. Diffuse parakeratosis, that
      occasionally arose abruptly from normal epidermis, was observed in 12 biopsy
      specimens. By the time necrolytic migratory erythema was diagnosed, the
      pancreatic carcinoma had metastasized to the liver, regional lymph nodes, or bone
      in 12 patients. CONCLUSION: Increased awareness of the polymorphic mucocutaneous
      and nonspecific histopathologic features of glucagonoma syndrome is needed to
      avoid unnecessary delay in the diagnosis of this syndrome.

PMID- 14693016
TI  - Diagnostic, prognostic and pathogenic value of the direct immunofluorescence test
      in cutaneous leukocytoclastic vasculitis.
AB  - BACKGROUND: No precise studies have been performed on cutaneous leukocytoclastic
      vasculitis (LV) to establish whether it is better to obtain a skin biopsy from
      lesional or from perilesional skin for direct immunofluorescence (DIF). There is
      no agreement on the immunoglobulins most frequently detected and the value of DIF
      for the classification of cutaneous vasculitis. METHODS: A prospective study of
      DIF in lesional and perilesional skin was performed in 50 leukocytoclastic
      vasculitis patients and 15 nonvasculitis patients. RESULTS: We detected a higher
      level of positivity in involved skin than in uninvolved skin for IgG, IgA, IgM,
      C3 and fibrinogen but not for C1q. In vasculitic patients, IgA was the
      immunoglobulin most frequently detected in lesional (82%) and perilesional skin
      (68%), followed by IgM (56 and 34%, respectively) and IgG (20 and 8%,
      respectively). Only IgA deposits were associated with the diagnosis of
      vasculitis, with a sensitivity of 82% in lesional and 68% in perilesional skin,
      and with a specificity of 73 and 66.7%, respectively. The presence of IgA in
      lesional skin was associated with renal involvement but there was no association
      with severity. The presence of IgG or IgM, or the absence of IgA in perilesional
      skin was related to the presence of cryoglobulins. The absence of IgA in lesional
      and perilesional skin was also related to hepatitis C virus infection.
      CONCLUSIONS: DIF findings in involved skin are more closely related to the
      diagnosis of vasculitis and can give more information about overall renal
      involvement than findings in uninvolved skin. However, findings in uninvolved
      skin are more closely related to the pathogenic factors that trigger the
      development of vasculitis.

PMID- 14693017
TI  - Contribution of sexually transmitted diseases and socioeconomic factors to
      perinatal mortality in rural Ghana.
AB  - BACKGROUND: The infant mortality rate is higher in sub-Saharan Africa than in
      other developing regions. The purpose of this study was to evaluate the
      association of sexually transmitted diseases (STDs) and socioeconomic and
      obstetric factors with perinatal mortality in rural Ghana. METHODS: Perinatal
      mortality data were collected from 154 patient records of the outpatient and
      inpatient gynecology department of a rural Ghanaian setting in 1997. All women
      attended the antenatal care unit of the hospital at least once before delivery,
      where they were screened for common STDs, including syphilis, gonorrhea, and
      trichomoniasis. Patients' socioeconomic characteristics and previous obstetric
      complications were recorded. RESULTS: The rate of perinatal mortality at the Holy
      Family Hospital in the Berekum district of Ghana was 13.7% in 1997 (154 of 1123
      documented births). Characteristics of mothers whose infants died in the
      perinatal period and who had attended antenatal care at least once were as
      follows: prior obstetric complications, 108 patients (70.1%); average age, 25
      years (range: 16-42 years); average number of previous sexual partners, three;
      prevalence of STDs, including gonorrhea, trichomoniasis, or syphilis, 83 patients
      (53.8%); history of other chronic diseases, 13 patients (8.5%); and illiteracy,
      66 patients (42.8%). The number of previous sexual partners and illiteracy were
      higher in the STD-positive women. CONCLUSIONS: Sexually transmitted diseases and
      previous obstetric complications seemed to contribute considerably to perinatal
      mortality in rural Ghana.

PMID- 14693018
TI  - Prevalence of skin diseases in Ibadan, Nigeria.
AB  - AIM: To study the pattern of skin diseases in patients attending the skin clinic
      of the University College Hospital, Ibadan, Nigeria, and to compare our findings
      with studies performed earlier in the same clinic. PATIENTS AND METHODS: The
      study involved 1091 new patients who had attended the skin clinic of the
      University College Hospital, Ibadan, Nigeria, between January 1994 and December
      1998. The patients were examined by the authors, and laboratory investigations
      were ordered when necessary to make a diagnosis. RESULTS: An increased prevalence
      of eczema, idiopathic pruritus, urticaria, connective tissue diseases, and fixed
      drug eruptions was observed. Infections, such as scabies, candidiasis, and tinea
      versicolor, had also increased. Pyoderma, leprosy, onchocerciasis, and
      dermatophytoses showed a decline. Psoriasis was uncommon, although there was a
      slight increase in prevalence. Vitiligo and alopecia were stable. Cutaneous
      tuberculosis, such as lupus vulgaris, was rare. CONCLUSIONS: Allergic conditions
      have increased; connective tissue disorders, such as systemic lupus
      erythematosus, scleroderma, and discoid lupus erythematosus, have also increased.
      Cutaneous disorders associated with human immunodeficiency virus infection, such
      as seborrheic dermatitis, have increased. Health workers need to be educated on
      the management and treatment of these conditions, and should be advised to refer
      patients to appropriate health facilities when necessary.

PMID- 14693019
TI  - Acral lentiginous melanoma misdiagnosed as tinea pedis: a case report.
AB  - The incidence of acral lentiginous melanoma (ALM) varies in different ethnic
      groups. Volar skin is a relatively infrequent site of malignant melanoma in
      Caucasian patients, although the foot is the most common site of involvement in
      Asian and African populations. Diagnosis of ALM is usually delayed and melanomas
      can be diagnosed at advanced clinical stages, so the prognosis is often poor. We
      present a Caucasian Turkish man with ALM on the interdigital site of his foot,
      however, as a result of maceration of the surrounding skin, it seemed to be tinea
      pedis.

PMID- 14693020
TI  - Erythroderma/exfoliative dermatitis: a synopsis.

PMID- 14693021
TI  - Acute hemorrhagic edema of infancy: a case report.
AB  - BACKGROUND: Acute hemorrhagic edema of infancy (AHEI), or Seidlmayer's disease,
      is a type of leukocytoclastic vasculitis proper of infants and children. It is
      characterized by a local increase in temperature, erythematous edema and purpuric
      lesions involving mainly the face and extremities. There usually is no visceral
      involvement. The disease is self-limited, bearing a benign clinical course.
      Infection, drugs and immunization have been considered as precipitating factors.
      The main differential diagnosis is Henoch-Schonlein purpura (HSP). METHODS: We
      describe a classic example of acute hemorrhagic edema of infancy, and comment on
      the clinical features, pathology, immunopathology and proposed therapy. We
      characterize the differences between AHEI and HSP. RESULTS: A course of
      corticosteroids was given to avoid quick progression of disease. CONCLUSION:
      Acute hemorrhagic edema of infancy is a rare disease, and the most striking
      classic feature of the disease is the contrast between the acuteness of the
      cutaneous lesions and the good general condition of the patient. Considering its
      clinical features, pathology and immunopathology, AHEI can be justifiably
      characterized as a unique disorder, distinct from HSP.

PMID- 14693022
TI  - Carbamazepine-induced DRESS syndrome with recurrent fever and exanthema.

PMID- 14693023
TI  - Malignant giant cell tumor of the tendon sheath.

PMID- 14693024
TI  - Sweet's syndrome associated with cytomegalovirus infection.

PMID- 14693025
TI  - Suggestion for the treatment of steatocystoma multiplex located exclusively on
      the face.
AB  - BACKGROUND: Although there are numerous reports of different treatment methods,
      the long-term management of steatocystoma multiplex remains difficult. In this
      article we describe a simple technique that we used to treat the cysts on the
      face of a patient. METHODS: A 31-year-old male with steatocystoma multiplex
      located on the forehead and both temples was treated by inserting the tip of a
      needle and extirpating the contents, without removing the cyst wall. RESULTS: The
      procedure was very well tolerated by the patient. There have been no
      complications during or following the procedure. There were no recurrences after
      10 months of follow up. CONCLUSIONS: We suggest that this very simple technique
      is worth trying as a treatment of choice, especially for the management of facial
      lesions, where scarring is unacceptable.

PMID- 14693026
TI  - Itraconazole in the treatment of seborrheic dermatitis: a new treatment modality.
AB  - BACKGROUND: Due to the high rate of recurrence, seborrheic dermatitis (SD)
      represents a therapeutic problem. AIM: To evaluate the role of oral itraconazole
      in the treatment of SD. PATIENTS AND METHODS: Thirty-two patients with SD were
      enrolled in the study. All topical and oral treatments were stopped. The patients
      applied 1% hydrocortisone cream twice daily for 1 month. In addition, they took
      itraconazole, 200 mg/day, during the first week of the first month and then
      hydrocortisone cream was stopped and itraconazole (200 mg/day) was given on the
      first 2 days of the following 11 months. The patients were followed for 2 months
      without medicine. The severity score was measured at the initial evaluation, and
      at the first, 12th, and 14th months. RESULTS: Twenty-eight patients completed the
      study. There was a statistically significant decrease in the mean severity score
      at the first, 12th, and 14th months. On the final evaluation at the 12th month,
      19 of the 28 patients showed a complete improvement, and three patients showed a
      slight improvement. CONCLUSIONS: This study indicates that itraconazole plays an
      important role in the treatment of SD.

PMID- 14693027
TI  - Erythema multiforme associated with phenytoin and cranial radiation therapy: a
      report of three patients and review of the literature.
AB  - BACKGROUND: Intracranial malignancies (primary and metastatic) are often
      complicated by seizure activity. Phenytoin (Dilantin) is typically employed as
      prophylactic anticonvulsant in this setting. Uncommonly, erythema multiforme (EM)
      can develop in such patients at the port site during or soon after cranial
      radiation and can rapidly progress to EM major. Herein, in addition to a
      comprehensive literature review of this entity, three additional patients are
      presented. The acronym 'EMPACT' is suggested (E: erythema; M: multiforme;
      associated with P: phenytoin; A: and; C: cranial, radiation; T: therapy) to best
      describe this disorder. METHODS: An extensive review of the English medical
      literature through the National Library of Medicine (PUBMED) was performed to
      identify patients who had received or continued to receive radiation therapy
      while on phenytoin. A total of 24 patients were identified and clinical
      information of varying detail was available in all cases. Clinical and
      histological information on three additional patients seen at two institutions
      (Rochester Methodist Hospital, Rochester, MN, and Fairview-University Medical
      Center, Minneapolis, MN) by the authors were also compiled. RESULTS: The mean age
      was 44 years (range: 23-67) and no sexual predisposition was noted. All patients
      had taken phenytoin for variable time periods (range 16-80 days; mean: 40) and
      were on the medication when the skin lesions first appeared. These lesions
      developed within the port site during the radiation treatments (11 cases) or soon
      after (nine cases) its completion (mean: 16 days; range: 2-35). Subsequent
      disease evolution to EM major occurred in all cases (Stevens-Johnsons syndrome
      developed in 73% of patients). No relationship was identified between the extent
      and the severity of the skin lesions with the phenytoin and radiation dosages and
      with the histologic type and origin of the intracranial malignancy. None of the
      patients demonstrated the requisite features of the 'Dilantin hypersensitivity
      syndrome'. Although, a systemic steroid taper was employed in 10 out of the 14
      patients before the development of the skin lesions, the subsequent progression
      of the skin lesions was not influenced by the use of systemic steroid therapy.
      Complete recovery occurred in all but two patients typically within 1-8 weeks of
      discontinuation of phenytoin. CONCLUSIONS: The need for prophylactic
      anticonvulsant therapy especially utilizing phenytoin in patients undergoing
      cranial radiation therapy should be assessed on a case by case basis. If
      anticonvulsants are employed, then they must be administered with caution, and
      all cutaneous reactions developing subsequently within the radiation site must be
      promptly evaluated with a high index of suspicion for erythema multiforme.

PMID- 14693028
TI  - Ethical aspects of the relationship of dermatology and industry: the Independent
      Ethics Committee.

PMID- 14693029
TI  - Transverse nail ridging (Beau's lines) and rough nails after bone marrow
      transplantation.

PMID- 14693030
TI  - Serotonin in alopecia areata: an enzyme immunoassay study.

PMID- 14693033
TI  - Synchronous sebaceous lymphadenoma with squamous cell carcinoma - case report.
AB  - BACKGROUND: Sebaceous lymphadenoma is a rare benign salivary gland tumour of
      uncertain histogenesis. So is synchronous occurrence of two benign or malignant
      neoplasms. CASE-REPORT: 68-year-old female presented with right side parotid
      swelling associated with pain and gradual increase is size. Fine needle
      aspiration cytology of parotid swelling was suggestive of pleomorphic adenoma.
      Total conservative parotidectomy was performed and histopathology of the specimen
      revealed sebaceous lymphadenoma with squamous cell carcinoma. CONCLUSIONS:
      Sebaceous lymphadenoma and squamous cell carcinoma are two rare benign and
      malignant neoplasms arising in parotid gland. Synchronous occurrence of these two
      entities has not been reported.

PMID- 14693034
TI  - Peripheral nerve magnetic stimulation: influence of tissue non-homogeneity.
AB  - BACKGROUND: Peripheral nerves are situated in a highly non-homogeneous
      environment, including muscles, bones, blood vessels, etc. Time-varying magnetic
      field stimulation of the median and ulnar nerves in the carpal region is studied,
      with special consideration of the influence of non-homogeneities. METHODS: A
      detailed three-dimensional finite element model (FEM) of the anatomy of the wrist
      region was built to assess the induced currents distribution by external magnetic
      stimulation. The electromagnetic field distribution in the non-homogeneous domain
      was defined as an internal Dirichlet problem using the finite element method. The
      boundary conditions were obtained by analysis of the vector potential field
      excited by external current-driven coils. RESULTS: The results include evaluation
      and graphical representation of the induced current field distribution at various
      stimulation coil positions. Comparative study for the real non-homogeneous
      structure with anisotropic conductivities of the tissues and a mock homogeneous
      media is also presented. The possibility of achieving selective stimulation of
      either of the two nerves is assessed. CONCLUSION: The model developed could be
      useful in theoretical prediction of the current distribution in the nerves during
      diagnostic stimulation and therapeutic procedures involving electromagnetic
      excitation. The errors in applying homogeneous domain modeling rather than real
      non-homogeneous biological structures are demonstrated. The practical
      implications of the applied approach are valid for any arbitrary weakly
      conductive medium.

PMID- 14693035
TI  - Clinical Evidence: a useful tool for promoting evidence-based practice?
AB  - BACKGROUND: Research has shown that many healthcare professionals have problems
      with guidelines as they would prefer to be given all relevant information
      relevant to decision-making rather than being told what they should do. This
      study assesses doctors' judgement of the validity, relevance, clarity and
      usability of the Italian translation of Clinical Evidence (CE) after its free
      distribution launched by the Italian Ministry of Health. METHODS: Opinions
      elicited using a standardised questionnaire delivered either by mail or during
      educational or professional meetings. RESULTS: Twenty percent (n = 1350) doctors
      participated the study. Most of them found CE's content valid, useful and
      relevant for their clinical practice, and said CE can foster communications among
      clinicians, particularly among GPs and specialists. Hospital doctors (63%) more
      often than GPs (48%) read the detailed presentation of individual chapters.
      Twenty-nine percent said CE brought changes in their clinical practice. Doctors
      appreciated CE's nature of an evidence-based information compendium and would
      have not preferred a collection of practice guidelines. CONCLUSIONS: Overall, the
      pilot initiative launched by the Italian Ministry of Health seems to have been
      well received and to support the subsequent decision to make the Italian edition
      of Clinical Evidence concise available to all doctors practising in the country.
      Local implementation initiatives should be warranted to favour doctor's use of
      CE.

PMID- 14693036
TI  - Public opinion regarding earmarked cigarette tax in Taiwan.
AB  - BACKGROUND: Cigarette taxation has been perceived by academics and policy-makers
      as one of the most effective ways of reducing the use of cigarettes. On January 1
      2002, the Taiwan government imposed a New Taiwan (NT) 5 dollars per pack tax
      earmarked for the purpose of tobacco control. This study uses a survey collected
      prior to taxation to assess public attitudes toward cigarette taxation, public
      beliefs about the effectiveness of cigarette taxation at reducing cigarette use
      and public opinions about the allocation of this tax revenue. METHODS: Data were
      drawn from a national face-to-face interview on cigarette consumption in 2000. A
      total of 3,279 adults were aged 18 to 64 years; 49.9% of whom were male and 50.1%
      female, and with a smoking prevalence of 49.1% and 4.1%, respectively. The
      attitudes toward cigarette tax were analysed using multi-logit regressions. We
      analysed by logistic regression the potential changes in smoking behaviour that
      smokers might make in response to the five NT (New Taiwan) dollar earmarked tax
      on cigarettes per pack. We summarized public opinions about the allocation of
      earmarked tax revenue using descriptive statistics. RESULTS: Current smokers (OR
      = 0.34) and former smokers (OR = 0.68) were less likely to support the cigarette
      tax than non-smokers. A favourable attitude toward the tax was positively
      associated with personal monthly income, especially among females. Among male
      smokers, the possibility of reducing/quitting smoking in response to the five-NT
      dollar tax was negatively associated with the monthly expense for smoking. The
      two most frequently-suggested areas to receive money from the revenue collected
      from the earmarked tax were health education and cancer subsidy. CONCLUSIONS:
      Smoking status and economic factors determine the attitude and potential
      responses of people toward the cigarette tax. Taiwan's five NT-dollar earmarked
      tax for cigarettes may have only a limited effect upon the reduction in cigarette
      use.

PMID- 14693037
TI  - Does the risk of cerebral palsy increase or decrease with increasing gestational
      age?
AB  - BACKGROUND: It is generally accepted that the risk of cerebral palsy decreases
      with increasing gestational age of live born infants. However, recent studies
      have shown that cerebral palsy often has prenatal antecedents including
      congenital malformations, vascular insults and maternal infection. Cerebral palsy
      is therefore better viewed as occurring among fetuses, rather than among infants.
      We explored the epidemiologic implications of this change in perspective.
      METHODS: We used recently published data from Shiga Prefecture, Japan and from
      North-East England to examine the pattern of gestational age-specific rates of
      cerebral palsy under these alternative perspectives. We first calculated
      gestational age-specific rates of cerebral palsy as per convention, by dividing
      the number of cases of cerebral palsy identified among live births within any
      gestational age category by the number of live births in that gestational age
      category. Under the alternative formulation, we calculated gestational age
      specific rates of cerebral palsy by dividing the number of cases of cerebral
      palsy identified among live births within any gestational age category by the
      number of fetuses who were at risk of being born at that gestation and being
      afflicted with cerebral palsy. RESULTS: Under the conventional formulation,
      cerebral palsy rates decreased with increasing gestational age from 63.9 per
      1,000 live births at <28 weeks gestation to 0.9 per 1,000 live births at 37 or
      more weeks gestation. When fetuses were viewed as potential candidates for
      cerebral palsy, cerebral palsy rates increased with increasing gestational age
      from 0.08 per 1,000 fetuses at risk at <28 weeks gestation to 0.9 per 1,000
      fetuses at risk at 37 or more weeks gestation. CONCLUSIONS: The fetuses-at-risk
      approach is the appropriate epidemiologic formulation for calculating the
      gestational age-specific rate of cerebral palsy from a causal perspective. It
      shows that the risk of cerebral palsy increases as gestational duration
      increases. This compelling view of cerebral palsy risk may help refocus research
      aimed at understanding and preventing cerebral palsy.

PMID- 14693038
TI  - An improved microtiter assay for evaluating anti-HIV-1 neutralizing antibodies
      from sera or plasma.
AB  - BACKGROUND: The anti-HIV-1 neutralizing antibody assay is widely used in AIDS
      vaccine research and other experimental and clinical studies. The vital dye
      staining method applied in the detection of anti-HIV-1 neutralizing antibody has
      been used in many laboratories. However, the unknown factor(s) in sera or plasma
      affected cell growth and caused protection when the tested sera or plasma was
      continuously maintained in cell culture. In addition, the poor solubility of
      neutral red in medium (such as RPMI-1640) also limited the use of this assay.
      METHODS: In this study, human T cell line C8166 was used as host cells, and 3
      (4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) instead of
      neutral red was used as vital dye. In order to avoid the effect of the unknown
      factor(s), the tested sera or plasma was removed by a washout procedure after
      initial 3-6 h culture in the assay. RESULT: This new assay eliminated the effect
      of the tested sera or plasma on cell growth, improved the reliability of
      detection of anti-HIV-1 neutralizing antibody, and showed excellent agreement
      with the p24 antigen method. CONCLUSION: The results suggest that the improved
      assay is relatively simple, highly duplicable, cost-effective, and well reliable
      for evaluating anti-HIV-1 neutralizing antibodies from sera or plasma.

PMID- 14693039
TI  - Back to thiazide-diuretics for hypertension: reflections after a decade of
      irrational prescribing.
AB  - BACKGROUND: Whether newer antihypertensive drugs, such as calcium channel
      blockers, angiotensin converting enzyme inhibitors and alpha blockers are more
      effective than thiazides and beta blockers in preventing coronary disease, has
      been debated for years. DISCUSSION: Recently several trials addressing this issue
      have been finalised, and they provide a convincing answer: the newer drugs are no
      better than the older ones. In the largest trial to date (ALLHAT), thiazide-type
      diuretic was found to offer advantages over newer drugs. The medical community
      should now be capable of reaching consensus, and recommend thiazides as the first
      line therapy for the treatment of hypertension. Prescribing physicians,
      cardiologists, drug companies and health authorities are all partly responsible
      for the years of irrational prescribing that we have witnessed. SUMMARY: All
      stakeholders should now contribute in order to achieve what is clearly in the
      public's interest: implementing the use of thiazides in clinical practice.

PMID- 14693040
TI  - The temporal relationship between reduction of early imitative responses and the
      development of attention mechanisms.
AB  - BACKGROUND: To determine whether early imitative responses fade out following the
      maturation of attentional mechanisms, the relationship between primitive
      imitation behaviors and the development of attention was examined in 4-month-old
      infants. They were divided into high and low imitators, based on an index of
      imitation. The status of attention was assessed by studying inhibition of return
      (IOR). Nine-month-old infants were also tested to confirm the hypothesis.
      RESULTS: The IOR latency data replicate previous results that infants get faster
      to produce a covert shift of attention with increasing age. However, those 4
      month-olds who showed less imitation had more rapid saccades to the cue before
      target presentation. CONCLUSION: The cortical control of saccade planning appears
      to be related to an apparent drop in early imitation. We interpret the results as
      suggesting a relationship between the status of imitation and the neural
      development of attention-related eye movement.

PMID- 14693041
TI  - Equine estrogens differentially inhibit DNA fragmentation induced by glutamate in
      neuronal cells by modulation of regulatory proteins involved in programmed cell
      death.
AB  - BACKGROUND: Recent data indicate that excitotoxicity of high levels of
      neurotransmitter glutamate may be mediated via programmed cell death (apoptosis)
      and that it can be prevented in HT22 mouse hippocampal cells by various equine
      estrogens with Delta8,17beta-estradiol (Delta8,17beta-E2) being the most potent.
      In order to delineate the mechanism(s), glutamate-induced cell death of HT22
      cells was assessed by measuring (a) DNA fragmentation in the presence or absence
      of 11 equine estrogens (components of the drug CEE); (b) cell death and (c)
      levels of anti-apoptotic (Bcl-2) and proapoptotic (Bax) proteins in the presence
      or absence of two equine estrogens, Delta8,17beta-E2 and 17beta-estradiol (17beta
      E2) by LDH release assay and Western blot analysis respectively. RESULTS:
      Glutamate treatment induced cell death was time and dose-dependent. After 18 to
      24 h, glutamate induced DNA fragmentation and morphological characteristics of
      apoptotic cell death. DNA fragmentation and morphological changes induced by 10
      mM glutamate were completely inhibited by some equine estrogens. Exposure of
      cells to various concentrations of glutamate, resulted in a significant increase
      in cell death associated LDH release that was time-dependent. Both Delta8,17beta
      E2 and 17beta-E2 inhibited the glutamate-induced LDH release and cell death in a
      dose-dependent manner with Delta8,17beta-E2 being 10 times more potent than
      17beta-E2. Western blot analysis indicated that glutamate also significantly
      decreased the levels of Bcl-2 and increased Bax levels. This glutamate-induced
      change in the ratio of Bcl-2 to Bax was reversed by estrogens with Delta8,17beta
      E2 being more potent. CONCLUSIONS: In HT22 mouse hippocampal cells, glutamate
      induced apoptosis that was associated with DNA fragmentation, morphological
      changes and up-regulation of the pro-apoptotic protein Bax and down-regulation of
      the anti-apoptotic protein Bcl-2. This apoptotic process was differentially
      prevented by some equine estrogens with Delta8,17beta-E2 being more potent than
      17beta-E2. Since HT22 cells lacked both glutamate and estrogen receptors, the
      neuroprotective effects of estrogens most likely involve both genomic and non
      genomic mechanisms. Since Delta8-estrogens are less feminizing estrogens than
      17beta-E2, further chemical modifications of these Delta8-estrogens may provide
      more selective estrogens that will be useful in the prevention of
      neurodegenerative diseases such as Alzheimer's and Parkinson's in both aging men
      and women.

PMID- 14693044
TI  - [Immunoscintigraphy of anti-type IV collagenase monoclonal antibody in nude mice
      bearing human lung cancer xenograft].
AB  - BACKGROUND & OBJECTIVE: Matrix metalloproteinases (MMPs)play the important role
      in many steps of tumor growth and metastasis. Type IV collagenase, which is a key
      member of MMPs family, has been viewed as a promising target in tumor study. The
      aim of this study was to evaluate the tumor-specific distribution of the anti
      type IV collagenase monoclonal antibody (mAb) 3G11 by radioimaging in tumor
      bearing nude mice. METHODS: MAb 3G11 purified by affinity chromatography was
      labeled with either 131- or 125- iodide by the Iodogen method. Immunoreactivity
      of mAb 3G11 was determined by ELISA. (131)I-labeled 3G11 was incubated in three
      different media at 37 Celsius degree and its in vitro stability was tested.
      Normal BALB/c mice were injected intravenously with 388.5 kBq per mouse of (125)I
      labeled 3G11 to explore the pharmacokinetic patterns. The scintigraphic images of
      human lung carcinoma PG xenografts grown subcutaneously in BALB/c nude mice were
      made after intravenously administrating of 6.44 MBq per mouse of (131)I-labeled
      3G11. RESULTS: MAb 3G11 was more than 98% in purity via affinity purification.
      The immunoreactivity of mAb 3G11 decreased by approximately 10%-20% after cold
      iodination. Patterns of blood clearance of mAb 3G11 was defined as two
      compartment model, with T(1/2alpha) and T(1/2beta) calculated to be 7.2 h and
      345.2 h, respectively. (131)I-labeled 3G11 was almost stable in vitro for 72 h. A
      clear image of the xenografted tumor was obtained at 72 h, and it further
      improved at 120 h. CONCLUSION: MAb 3G11 showed high specificity and affinity with
      tumor tissue through scintiscanning.

PMID- 14693042
TI  - Fast and sensitive multiple alignment of large genomic sequences.
AB  - BACKGROUND: Genomic sequence alignment is a powerful method for genome analysis
      and annotation, as alignments are routinely used to identify functional sites
      such as genes or regulatory elements. With a growing number of partially or
      completely sequenced genomes, multiple alignment is playing an increasingly
      important role in these studies. In recent years, various tools for pair-wise and
      multiple genomic alignment have been proposed. Some of them are extremely fast,
      but often efficiency is achieved at the expense of sensitivity. One way of
      combining speed and sensitivity is to use an anchored-alignment approach. In a
      first step, a fast search program identifies a chain of strong local sequence
      similarities. In a second step, regions between these anchor points are aligned
      using a slower but more accurate method. RESULTS: Herein, we present CHAOS, a
      novel algorithm for rapid identification of chains of local pair-wise sequence
      similarities. Local alignments calculated by CHAOS are used as anchor points to
      improve the running time of DIALIGN, a slow but sensitive multiple-alignment
      tool. We show that this way, the running time of DIALIGN can be reduced by more
      than 95% for BAC-sized and longer sequences, without affecting the quality of the
      resulting alignments. We apply our approach to a set of five genomic sequences
      around the stem-cell-leukemia (SCL) gene and demonstrate that exons and small
      regulatory elements can be identified by our multiple-alignment procedure.
      CONCLUSION: We conclude that the novel CHAOS local alignment tool is an effective
      way to significantly speed up global alignment tools such as DIALIGN without
      reducing the alignment quality. We likewise demonstrate that the DIALIGN/CHAOS
      combination is able to accurately align short regulatory sequences in distant
      orthologues.

PMID- 14693045
TI  - [Apoptosis of human B cell lymphoma Raji cells induced by monovalent anti-CD20
      antibody].
AB  - BACKGROUND & OBJECTIVE: The anti-CD20 antibodies and fragments have been applied
      for treatment of non-Hodgkin's lymphomas (NHL) in clinic. The new anti-CD20
      antibodies and their fragments (unmodified or radiolabeled) yet have been
      exploited for those patients with incomplete response to rituximab. The chimeric
      antibody fragments Fab and F(ab) '(2) derived from HI(47)(a mouse anti-CD20
      antibody) have been constructed. The present study was designed to determine the
      effect of HI(47) and chimeric anti-CD20 antibody fragments on growth inhibition
      and apoptosis of lymphoma cells. METHODS: The binding of anti-CD20 antibodies to
      CD20 positive human B cell lymphoma Raji cells was examined using
      immunofluorescence assay. MTT method was used to evaluate the effect of chimeric
      antibody fragments on Raji cells growth. Annexin V staining and DNA ladder were
      used to examine the apoptosis of Raji cells induced by chimeric antibody
      fragments. RESULTS: HI(47) and its chimeric antibody fragments were capable of
      binding to CD20 positive Raji cells with the binding rate of above 90%. HI(47)
      did not compete with rituximab in binding with Raji cells. The growth of Raji
      cells was inhibited by HI(47) and its fragments with the inhibition rates of
      (57+/-1.5)%, (65.2+/-2.5)%,and (77.2+/-3.2)%, respectively, at the concentration
      of 100 microg/ml. The monovalent antibody fragment Fab (20 microg/ml) induced the
      apoptosis of Raji cells with early apoptosis rate of 17%. CONCLUSION: The
      chimeric anti-CD20 antibody fragments derived from HI(47) have inhibitory effect
      on Raji cells and can induce apoptosis of Raji cells.

PMID- 14693046
TI  - [Effects of two LMP1 variants on resistance of CNE1 cell strain to TGF-beta1].
AB  - BACKGROUND & OBJECTIVE: We had proved that different latent membrane protein 1
      (LMP1) variants of Epstein-Barr virus (EBV) had different effects upon growth
      characteristics of a human well-differentiated nasopharyngeal carcinoma (NPC)
      cell strain CNE1. This study was designed to investigate the possible effects of
      different LMP1 variants on resistance of CNE1 to TGFbeta1 and the related
      mechanism(s) so as to further elucidate the intrinsic mechanisms of their growth
      promoting effects upon CNE1. METHODS: The plasmids including J124 (served as a
      control plasmid),124-B95-8 (carried LMP1 gene cloned from B95-8 lymphocytes,B95-8
      LMP1), and J124- CAO-5 (carried LMP1 gene cloned from NPC tissues,CAO-LMP1) were
      introduced into CNE1 by liposomal transfection. The transfected cell strains were
      named CNE1-V,CNE1-B,and CNE1-C,respectively. Gene and protein expression of LMP1
      in CNE1 were identified by reverse transcription-polymerase chain reaction (RT
      PCR) and Western blot analysis,respectively. Then growth inhibition assay using
      MTT colorimetric method and flow cytometry were conducted to investigate
      different effects of the two LMP1 variants on resistance of CNE1 to TGFbeta1.
      Meanwhile,TGFbetaRI,TGFbetaRII, and cyclin D1 were detected by Western blot
      analysis and p15 mRNA was examined by semi-quantitative RT-PCR. RESULTS: Two
      transfected cell strains (CNE1-B and CNE1-C) stably expressing different LMP1
      variants were established successfully. When the treating concentration of
      TGFbeta1 was 5 ng/ml, the growth inhibitory rates of CNE1, CNE1-V,CNE1-B,and CNE1
      C were 31.8%, 27.9%, 10.94%, and -4.26%, respectively, and the proliferation
      index (PI) were (24.55+/-2.55)%, (25.43+/-2.18)%, (46.78+/-2.56)%, and (54.70+/
      3.84)%, respectively. CAO-LMP1 induced complete TGFbeta1 resistance in CNE1,
      whereas B95-8-LMP1 induced partial resistance. Neither of the two LMP1 variants
      had effects on TGFbetaRI and TGFbetaRII protein expression in CEN1,whereas both
      of them induced cyclin D1 expression significantly. CAO-LMP1 induced higher level
      of cyclin D1 than B95-8-LMP1 did (P< 0.05). B95-8-LMP1 had no significant effect
      on p15 mRNA expression (P >0.05), whereas CAO-LMP1 down-regulated p15 mRNA level
      obviously (P< 0.05). CONCLUSION: B95-8-LMP1 could induce partial resistance of
      CNE1 to TGFbeta1 and the main mechanism was correlated with up-regulation of
      cyclin D1 protein, whereas CAO-LMP1 could induce complete resistance to TGFbeta1
      and the mechanisms were correlated with up-regulation of cyclin D1 protein as
      well as down-regulation of p15 mRNA.

PMID- 14693047
TI  - [Apoptotic induction of human lung carcinoma A549 cells by DFMO through Fas/FasL
      pathway].
AB  - BACKGROUND & OBJECTIVE: Fas/FasL pathway play an important role in cell
      apoptosis. To investigate the role of Fas/FasL system in polyamine biosynthesis
      inhibition and malignant phenotype reversion of carcinoma cells, we examined the
      effect of DFMO (alpha-difluoromethylornithine), an inhibitor of polyamine
      biosynthesis, on cell growth and apoptosis of A549 cells, and their association
      with human lung carcinoma-associated antigen, ras P21 protein, and Fas/FasL.
      METHODS: MTT assay,flow cytometry,and DNA fragmentation analysis were used to
      determine cell growth and apoptosis,respectively. The gene and protein expression
      were determined by reverse transcription polymerase chain reaction (RT-PCR) and
      immunohistochemical staining, respectively. RESULTS: DFMO could inhibit the
      growth of A549 cells and induce their apoptosis, meanwhile the cells in G(1)
      phase were increased with (61.0+/-2.08)%, the cells in S phase were decreased
      with (21.2+/-0.88)%, and DNA ladder were observed. Simultaneously, the expression
      of human lung carcinoma-associated antigen and ras P21 protein were
      downregulated, but Fas mRNA and protein expression were upregulated. CONCLUSION:
      DFMO induce apoptosis of human lung carcinoma A549 cells through Fas/FasL
      pathway. It might be correlated with the expression of human lung carcinoma
      associated antigen and ras P21 protein.

PMID- 14693048
TI  - [Killing effect of adenovirus vector-mediated herpes simplex virus thymidine
      kinase gene recombinant construct on various cancer cells].
AB  - BACKGROUND & OBJECTIVE: Adenovirus vector-mediated herpes simplex virus thymidine
      kinase gene (ADV-TK) transfer is one of the major gene therapy strategies for
      tumor. This study was designed to determine the in vitro anti-tumor efficiency of
      ADV-TK, a recombinant construct previously developed in our laboratory. METHODS:
      Herpes simplex virus thymidine kinase (TK) gene was transduced into 14 types of
      cultured tumor cells with different histological origins using adenovirus vector
      followed by ganciclovir (GCV) medication. The killing efficiency was measured
      using MTT assay. RESULTS: At the dosage of 1x10(9) viral particles/per well in
      the presence of 100 microg/ml GCV, ADV-TK/GCV caused effective killing of 11 out
      of total 14 types of tumor cells with a rate higher than 74%, the other 3 tumor
      cells, laryngeal epithelial cancer cells (Hep-2), hepatic cancer cells (Bel7402),
      and human colon cancer cells (HCT-8) were less sensitive to the ADV-TK/GCV
      treatment with the killing rates of 55.3%+/-2.0%, 61.3%+/-2.0%, and 63.7%+/-2.5%,
      respectively. Except for Hep-2, the killing efficiency caused by ADV-TK/GCV
      treatment was similar to that caused by cisplatin at a dosage equal to the in
      vivo peak concentration (5 microg/ml) in tissue. CONCLUSION: ADV-TK is highly
      efficient for active killing of tumor cells in vitro and is promising for future
      clinical application.

PMID- 14693049
TI  - [Effect of allitridi on cyclin D1 and p27(Kip1) protein expression in gastric
      carcinoma BGC823 cells].
AB  - BACKGROUND & OBJECTIVE: Previous study showed that allitridi markedly suppresses
      cellular proliferation, blocks cell cycle at G(1) phase, and induces cell
      apoptosis of human gastric cancer BGC823 cell. During the investigation of its
      molecular mechanisms and target genes, the authors found that protein expression
      of cyclin D1 and p27(Kip1) play an important role in an allitridi-induced G(1)
      arrest. This study was designed to explore the effect of allitridi on the
      expression of cyclin D1 and p27(Kip1) in BGC823 cells. METHODS: After total RNA
      and total protein in allitridi-treated (25 microg/ml) and allitridi-untreated
      BGC823 cells were abstained, Western blot analysis was performed to determine the
      protein levels of cyclin D1 and p27(Kip1), and RT-PCR was performed to determine
      the mRNA levels of cyclin D1 and p27(Kip1). RESULTS: After treated with 25
      microg/ml allitridi for 24 hours, the protein levels of cyclin D1 of BGC823 cells
      were downregulated and the protein levels of p27(Kip1) were upregulated, and this
      changes were more obvious after 48 hours,while their mRNA levels remained
      unchanged. CONCLUSION: Allitridi may influence the protein expression of cyclin
      D1 and p27(Kip1) in BGC823 cells, while do not influence their mRNA
      transcription.

PMID- 14693050
TI  - [Effect of genistein on proliferation of renal cell carcinoma cell line GRC-1 and
      its influence to p27 expression].
AB  - BACKGROUND & OBJECTIVE: There has always been a significant morbidity difference
      of renal cell carcinoma between the Oriental and Occidental countries. The high
      soybean consumption in Oriental countries may be one of the reasons. We
      investigated the effect of a tyrosine protein kinase inhibitor extracted from
      soybean, namely genistein, on the proliferation of a renal cell carcinoma cell
      line, GRC-1; and analyzed the correlation between this effect and a well-known
      anti-oncogene, p27. METHODS: Inverted microscopy, MTT method, and flow cytometry
      (FCM) were used to examine the changes in proliferation of GRC-1 cells after
      treatment with genistein; and the intracellular p27 protein expression was
      determined by Western blot analysis. RESULTS: (1)After treatment with genistein,
      changed morphology of the GRC-1 cells was observed. Cell junctions decreased. In
      the presence of 20 micromol/L genistein, GRC-1 cells showed shuttle-shaped, and
      fewer pseudopodia, mitoses and cell junctions were observed. In the 40 micromol/L
      genistein group, many cells broke into debris, and became extremely irregular in
      shape. Meanwhile, mitoses and cell junctions were rarely seen. (2)Treated with 20
      micromol/L genistein, 73.8% GRC-1 cells were in G(1) phase, 26.2% in G2 phase 72
      hours after treatment; while in control group, 31.6% in G(1) phase and 3.8% in G2
      phase, respectively. (3)After exposure to 20 micromol/L genistein for 72 hours,
      Western blot suggested that the band of p27 was 65.4+/-4.7 in gray scale value,
      while the control group was 52.3+/-6.3. CONCLUSION: Genistein can inhibit the
      proliferation of renal cell carcinoma cells, and cause cell cycle arrest at
      G(1)/M, G(2)/S phase. The possible underlying mechanism may involve its
      upregulation of p27 expression in the renal cancer cells.

PMID- 14693051
TI  - [Mechanism of arsenic trioxide-induced cytotoxicity on multiple myeloma cells].
AB  - BACKGROUND & OBJECTIVE: Multiple myeloma (MM), a plasma cell tumor, is difficult
      to cure by now. Previous study showed that As2O3 could inhibit the proliferation
      and induce the apoptosis of myeloma cell in vitro. The aim of this study was to
      explore the possible mechanism of arsenic trioxide (As2O3) on multiple myeloma
      cells. METHODS: The cytotoxic effects of As2O3 on five myeloma cell lines U266,
      SKO-007, LP-1, HS-Sultan, and KM3 were examined using MTT bioassay, and the
      concentration of 50% growth inhibition (IC(50)) was calculated. The synergistic
      or antagonistic effects of menadione (VK(3)), N-acetyl-cysteine (NAC), and
      reduced glutathione (GSH) combined with As2O3 were also examined. The cellular
      GSH levels in five MM cell lines and its changes in U266 cells after treated with
      As2O3, VK(3), NAC, and exogenous GSH were determined by colorimetric assay, and
      the relationship between IC(50) and cellular GSH levels was analyzed. RESULTS:
      As2O3 inhibited the proliferation of all five myeloma cells, but with different
      sensitivity. GSH contents in five MM cells were correlated with its IC(50)
      significantly (r=0.87,P< 0.05). Oxidant VK(3) had significant synergistic effect
      with As2O3, and antioxidants NAC and GSH partly blocked the growth inhibition of
      As2O3. Both As2O3 and VK(3) decreased the GSH contents, NAC and GSH increased
      them contrarily. CONCLUSION: One of the mechanisms of effect of As2O3 on myeloma
      cells may be through decreasing the cellular GSH levels and inducing myeloma cell
      apoptosis.

PMID- 14693052
TI  - [Apoptosis of human hepatoma HepG2 cells induced by emodin in vitro].
AB  - BACKGROUND & OBJECTIVE: Emodin (3-methyl-1,6,8-trihydro- xyanthrax-quinone) is
      the main effective composition of some Chinese herbs. Previous studies showed
      that emodin could inhibit the proliferation of some kind of tumor cells, such as
      breast cancer and lung cancer, while the mechanism(s) by which emodin suppresses
      tumor growth remains unknown. The study was designed to investigate the
      inhibitory effects and mechanisms of emodin-induced cell death in human hepatoma
      cell HepG2. METHODS: MTT assay was used to evaluate the IC(50) of emodin on HepG2
      cells. Through soft agar assay, the ability of cell proliferation when exposed to
      emodin at various dosages was detected. DNA fragmentation (ladder) and flow
      cytometry analysis were applied to investigate the effects and mechanisms of
      emodin on HepG2 cells. RESULTS: Emodin could inhibit the growth of HepG2 cells
      significantly with IC(50) of 36+/-2.6 microg/ml; and could inhibit the colony
      formation of the cells in soft agar. After treatment of emodin,extraction of
      cancer cells exhibited typical DNA fragmentation, and flow cytometry analysis
      showed apoptosis in a dosage- dependent manner. As the concentration of emodin
      raised from 10 microg/ml to 20 microg/ml,the ratio of apoptotic cells increased
      from 27.3% to 59.6%. Under the concentration of 40 microg/ml, there were almost
      no living cells detected. CONCLUSION: Emodin may inhibit the growth and
      proliferation of HepG2 cells through the way of apoptosis introduction.

PMID- 14693053
TI  - [Reversal of multidrug resistance of human hepatocarcinoma HepG2/Adm cells by
      high intensity focused ultrasound].
AB  - BACKGROUND & OBJECTIVE: The effects of ultrasound have been shown on increasing
      cell membrane permeability and thereby might promote cellular uptake of cytotoxic
      drugs and enhance chemotoxicity. The aim of this study was to examine the
      reversal effects of high intensity focused ultrasound (HIFU) and co
      administration with Adriamycin (ADM) on multidrug resistance (MDR) in HepG2/Adm
      cells, and to investigate its mechanism. METHODS: HepG2 cells and HepG2/Adm cells
      were divided into 4 groups: HepG2 (control group),HepG2 (treated with HIFU
      5s),HepG2/Adm (non HIFU), and HepG2/Adm (treated with HIFU 5s). MTT assay was
      used to examine the chemosensitivity to ADM in HIFU-treated HepG2 and HepG2/Adm
      cell lines. Before and after the treatment with HIFU 5s, MDR1 gene expression was
      determined by immunocytochemistry assay. Flow cytometry was used to determine
      intracellular ADM concentration and the expression of P-gp on cell membranes.
      RESULTS: HIFU (0.8MHz, 460W/cm2) partly overcame the MDR of cell line HepG2/Adm
      and decreased the drug resistance. The relative reverse efficiencies to ADM,
      cisplatin (DDP), mytomycin (MMC), 5-fluorouracil (5-FU), and methotrexate (MTX)
      were 66.4%, 63.4%, 89.4%, 72.4%, and 75.0%, respectively. While, the
      concentration of ADM in HepG2/Adm cells was increased by 88%. The expression of P
      glycoprotein (P-gp) protein in HepG2/Adm was down-regulated by 83.1%. CONCLUSION:
      HIFU can not only increase the ADM concentration in HepG2/Adm cells and decrease
      P-gp expression on cellular and nuclear membrane, but also partly overcome MDR of
      tumor cells.

PMID- 14693054
TI  - [Screening of the drug resistance-associated gene in HepG2 cell line transfected
      with aldose reductase like gene-1 (ARL-1)].
AB  - BACKGROUND & OBJECTIVE: Aldose reductase like gene-1 overexpresses in
      hepatocellular carcinomas; it might be the drug resistance- associated gene to
      anti-tumor drugs containing carbonyl groups on hepatocellular carcinomas. This
      study was designed to establish human hepatocellular carcinoma cell line (HepG2)
      transfected with aldose reductase like gene-1 (ARL-1), then to observe the
      changes of drug resistance to anti-tumor drugs with carbonyl group and screen the
      drug resistance-associated genes through cDNA chip. METHODS: PBK/ARL-1 plasmid
      was transfected to HepG2 cells by liposome to establish HepG2 monoclonal cells
      with high expression of ARL-1. The HepG2 cells with high expression of ARL-1 were
      determined by reverse transcription-polymerase chain reaction (RT-PCR),flow
      cytometric analysis (FCA), and immunohistochemical staining. MTT assay and cell
      apoptosis analysis were performed to determine the drug resistance ability of the
      cells to Adriamycin (ADM) and mytomycin (MMC), which contain carbonyl group. 5
      fluorouracil (5-FU) that has no carbonyl group was used as control. Then two
      kinds of cDNA probes were made from HepG2 cells and ARL-HepG2 cells and labeled
      with Cy3 and Cy5 dyes. The probes were hybridized to the human liver cDNA chip
      and differentially expressed genes from the two cells were screened. The genes
      could be involved in drug resistance were confirmed by RT-PCR and Western blot.
      RESULTS: Compared with HepG2 cells, HepG2 cells transfected with ARL-1 gene have
      an increase in expression of ARL-1. Drug resistance ability of HepG2 cells
      transfected with ARL-1 gene to ADM and MMC increased 2.6 and 3.47 folds,
      respectively (t=6.39, P< 0.05 in ADM group; t=30.06, P< 0.01 in MMC group). Drug
      resistance to 5-FU had no statistical difference between them (t=0.684,P >0.05 in
      5-FU group). 15 genes down-regulated and 9 genes up-regulated after transfected
      with ARL-1 gene were found by cDNA chip scanned. Some differentially displayed
      genes such as ubiquitin and MDR confirmed by RT-PCR and Western blot were
      consistent to the results of cDNA chip. CONCLUSION: The HepG2 cells with high
      expression of ARL-1 have more drug resistance to anti-tumor drugs with carbonyl
      group. Up-regulated MDR expression and down-regulated ubiquitin expression may
      contribute to the drug resistance of HepG2 cells.

PMID- 14693055
TI  - [Antisense oligonucleotide reverses topotecan-resistant ovarian cancer cells].
AB  - BACKGROUND & OBJECTIVE: Breast cancer resistance protein (BCRP) was overexpressed
      in topotecan (TPT)-selected human ovarian cancer cell line A2780/TPT, strongly
      suggesting BCRP to be responsible for the drug-resistance of ovarian cancer. The
      current study was designed to investigate the reversal effect of BCRP antisense
      oligonucleotide (ASODN) on topotecan- resistant A2780/TPT cells. METHODS: The
      antisense-phosphorothioate oligonucleotide including the translation initiation
      site of BCRP mRNA was artificially synthesized, and the sense oligonucleotide
      (SODN) corresponding to the ASODN was also synthesized as control. Lipofect-2000
      (LF) was used for the transfer of either ASODN or SODN into A2780/TPT cells. The
      changes of BCRP mRNA expression, intracellular fluorescence intensity of
      rhodamine and resistance index to topotecan of in vitro transfected A2780/TPT
      cells were detected respectively by reverse transcription-polymerase chain
      reaction (RT-PCR),flow cytometry (FCM),and methyl thiazolyl tetrazolium (MTT)
      assay. RESULTS: The transfer of ASODN/LF into A2780/TPT cells resulted in:(1)a
      59.42% reduction of BCRP mRNA level (P< 0.05); (2)an obviously increased
      intracellular rhodamine fluorescence intensity from 5.42 to 16.63(P< 0.05); (3)a
      decreased resistance index to topotecan from 25 to 5 indicating sensitivity to
      topotecan in A2780/TPT cells recovered, as compared with non-transfected cell.
      But after transfecting SODN, no significant change could be measured. CONCLUSION:
      ASODN transfection may partly reverse BCRP-mediated drug- resistance of ovarian
      cancer cells.

PMID- 14693056
TI  - [Effect of thalidomide on tumor growth in mouse hepatoma H22 model].
AB  - BACKGROUND & OBJECTIVE: Thalidomide may have curative effect on tumor because of
      its function of anti-angiogenesis. The aim of this research was to observe the
      effect of thalidomide on tumor homograft growth in mouse H22 model and to
      investigate the mechanisms involved and its curative possibility to hepatoma.
      METHODS: BALB/c mice were inoculated subcutaneously with H22 cells. The first
      treatment group was injected intraperitoneal everyday with thalidomide 50 mg/kg
      from the day of inoculation and the second treatment group was injected from the
      fourth day of inoculation. The diameters of the tumors were measured everyday. On
      the twelfth day, the mice were sacrificed and the tumors were weighed. The
      microvessel densities of the tumors were measured by immunohistochemical staining
      with anti-CD31 monoclonal antibody; CD31 expression, apoptosis, and proliferation
      were analyzed by flow cytometry. Expression of vascular endothelial growth factor
      (VEGF) mRNA was examined by reverse transcription-polymerase chain reaction (RT
      PCR). RESULTS: The tumor weight of the first treatment group (2.27+/-0.33 g) was
      decreased compared with that of control group (2.70+/-0.61 g) (P >0.05); the
      ratio of inhibition was 15.93%. The tumor weight of the second treatment group
      (3.32+/-0.47 g) was decreased compared with that of control group (3.42+/-0.60 g)
      (P >0.05); the ratio of inhibition was 2.92%. The microvessel count (48.40+/
      12.90) and CD31 expression (5.59+/-0.75) of the first treatment group were
      significantly decreased (P< 0.05) in comparison with those of control groups
      (81.20+/-26.91,7.04+/-0.50) (P< 0.05). The microvessel count (46.4+/-9.71) and
      CD31 expression (7.29+/-0.48) of the second treatment group were not
      statistically significant (P >0.05) compared with those of control groups (74.0+/
      32.69, 6.80+/-0.68) (P >0.05). The apoptosis indices of the two treatment groups
      (17.20+/-7.80,15.33+/-4.10) were significantly increased, compared with control
      groups (4.37+/-1.98,4.87+/-1.91) (P< 0.05), while there was no significant
      difference of VEGF mRNA expression between the two treatment groups and control
      groups (P >0.05). The relative quantities of VEGF mRNA of the two treatment
      groups were 0.50+/-0.13 and 0.51+/-0.06 (control groups:0.48+/-0.11 and 0.64+/
      0.11) (P >0.05), respectively. CONCLUSION: Thalidomide can significantly induce
      apoptosis and inhibit angiogenesis in mouse H22 model when it is used at the
      beginning of carcinogenesis, but it has no obvious anti-angiogenic efficacy on
      the grown tumor. Thalidomide cannot inhibit VEGF mRNA expression of grafted H22
      tumor in mouse.

PMID- 14693057
TI  - [Phase II clinical study of intratumoral H101, an E1B deleted adenovirus, in
      combination with chemotherapy in patients with cancer].
AB  - BACKGROUND & OBJECTIVE: In recent years,great development have been made in
      cancer therapeutics with replication-competent viruses (oncolytic viruses), E1B
      deleted adenovirus is one of promising viruses. The current study was designed to
      evaluate the efficacy and toxicity of intratumoral H101, a E1B-deleted
      adenovirus, in combination with chemotherapy on patients with cancer. METHODS: A
      total of 50 patients with malignant tumors in multiple centers clinical trial
      were treated with H101, 0.5ml 5x10(11) viral particle per day for 5 consecutive
      days every three weeks. Routine chemotherapy was performed at the same time. And
      the efficacy and toxicity were recorded. RESULTS: Among 46 valuable cases, the
      overall response rate was 30.4%. The response rate was 28.0% (14/50) among ITT
      population, including 3 complete response (CR) and 11 partial response (PR). The
      overall response rate of control lesion was 13.0%, including 1 case of CR and 5
      cases of PR. Thus, the response rate in injected lesion is clearly higher than
      that in control lesion (P< 0.001). Main side effects were injection site pain
      (26.9%) and fever (30.2%). Grade 1 hepatic dysfunction was found in 4 patients,
      grade 2 in 1 patients, grade 4 in 1 patients. Grade 4 hematological toxicities
      were found in 4 patients. CONCLUSION: The study showed that the combination of
      genetically modified adenovirus (H101) and chemotherapy possessed some effect for
      treating the patients with refractory malignant tumors, and the toxicities were
      lower, well tolerated.

PMID- 14693058
TI  - [Autologous peripheral blood stem cells mobilization with etoposide plus rhG-CSF
      versus cyclophosphamide plus rhG-CSF].
AB  - BACKGROUND & OBJECTIVE: It is important to get high quality autologous peripheral
      blood stem cell (APBSC) for successful peripheral blood stem cell
      transplantation. Cyclophosphamide (CTX) plus recombined human granulocyte colony
      stimulating factor (rhG-CSF) is standard regimen for APBSC mobilization.
      Etoposide plus rhG-CSF is another regimen for mobilization in recent years. The
      purpose of this study was to observe and compare the effects of these two
      regimens in APBSC mobilization for the patients with malignant lymphoma and germ
      cell tumors. METHODS: Fifty-two patients were divided into two groups according
      to the regimen of mobilization. In CTX group, 26 patients were injected CTX 3.5
      g/m(2) intravenously. The other 26 patients in VP-16 group, VP-16 1000 mg/m(2) or
      1500 mg/m(2) were given intravenously at random. All patients received rhG-CSF
      once daily as subcutaneous injection at the dose of 5 microg x kg(-1) x day(-1)
      from the day of the nadir of white blood cell (WBC) till the day before the last
      APBSC harvest in both groups. APBSC harvest was performed daily when WBC
      recovered more than 2.5x10(9)/L in CTX group and 5.0x10(9)/L in VP-16 group.
      APBSC harvest finished when accumulated mononuclear cells (MNCs) were more than
      5x10(8)/kg or CD34(+) cells were more than 2x10(6)/kg. Collected APBSC was
      infused following condition regimen. Blood parameters, account of harvested
      cells, the time of hematopoietic reconstitute, and adverse effects were compared
      between two groups. RESULTS: Following administration of CTX or VP-16, the nadirs
      of WBC and PLT in CTX group appeared significantly earlier than that in VP-16
      group. The doses and times of rhG-CSF administration were not significantly
      different between the two groups. The start was later and the times of APBSC
      apheresis were less significantly in VP-16 group. The processed blood volume in
      single apheresis was more in VP-16 group. Speed and duration of single apheresis
      were similar in the two groups. Total MNCs were similar in the two groups, but
      the numbers of MNCs and CD34(+) cells collected in the first harvest and total
      number of CD34(+) cells collected were significantly more in VP-16 group. With
      equal quantity infusion of MNCs and CD34(+) cells infusion, hematopoietic
      reconstitution was achieved in both groups and the time of reconstitution was
      similar. Nausea and vomiting were more frequent in CTX group. Obvious PLT
      decrease was observed in VP-16 group. Other adverse effects were similar.
      CONCLUSION: CTX or VP-16 plus rhG-CSF both were safe and effective regimens for
      APBSC mobilization. More CD34(+) cells can be harvested by mobilization with VP
      16 plus rhG-CSF than mobilization with CTX plus rhG-CSF. And the APBSC mobilized
      with VP-16 plus rhG-CSF can assure successful hematopoietic reconstitution.

PMID- 14693059
TI  - [Treatment of moderate-grade and high-grade malignant lymphoma with autologous
      hematopoietic stem cell transplantation].
AB  - BACKGROUND & OBJECTIVE: High dose chemotherapy (HDCT) supported by autologous
      hematopoietic stem cell transplantation (ASCT) is one of the most effective
      approaches for the chemo-sensitive lymphoma. The purpose of this study was to
      investigate the effectiveness of HDCT combined with radiotherapy supported by
      HSCT in treatment of poor- prognostic moderate-grade and high-grade malignant
      lymphoma. METHODS: Eleven patients [11 cases of non-Hodgkin's lymphoma (NHL) and
      2 cases of recurrent Hodgkin's lymphoma (HD)] were enrolled from December 1995 to
      May 2001. Status on ASCT was 8 cases with 1st complete remission (CR(1)), 4 cases
      with second complete remission (CR2), 1 case with second partial remission (PR2).
      The preparative regimens consisted of HDCT alone (4 patients), HDCT with involved
      field (IF) radiotherapy (6 patients), total body irradiation (TBI) with HDCT (3
      patients). Two patients were supported by bone marrow transplantation (ABMT) and
      11 by autologous peripheral blood stem cell transplantation (APBSCT). RESULTS:
      The numbers of mono-nuclear cell (MNC) and granulocyte- macrophage colony-forming
      cells (CFU-GM) reinfused were 2.55 (range, 2.07-3.31) x 10(9)/L, 1.43 (range, 0.6
      2.36) x 10(9)/L in this study, respectively. Hematopoietic reconstitution was
      observed in all patients when they were followed-up on October 2001. WBC>or=1.0 x
      10(9)/L and Platelet >50 x 10(9)/L were at day 6 (range,7-35) and day 8 (range,6
      32), respectively. The median CR duration was 16 months (range, 4-57 months). The
      1- and 3-year survival rates were 76.9% and 46.2%, respectively. CONCLUSION: HDCT
      with ASCT is valuable to treatment in patients with chemo-sensitive moderate
      grade and high-grade NHL and recurrent HD.

PMID- 14693060
TI  - [Induction of aGVHD after allogeneic hematopoietic stem cell transplantation for
      refractory or relapsed acute leukemia].
AB  - BACKGROUND & OBJECTIVE: Patients with refractory or relapsed acute leukemia after
      allogeneic hematopoietic stem cell transplantation had a poor prognosis with high
      death rate due to relapse or transplant-related mortality (TRM). The purpose of
      this paper was to clarify the role of inducing acute graft-versus-host disease
      (aGVHD) during transplantation in preventing relapse. METHODS: Thirty adult
      patients with refractory or relapsed leukemia were acute lymphoblastic leukemia
      (n=16), acute myelogenous leukemia (n=10), and acute mixed leukemia (n=4). They
      were in first complete remission (n=4), second complete remission (n=9), partly
      remission (n=12), and non-response (n=5) at the time of transplantation. Patients
      underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from
      HLA-identical siblings (n=21), mismatched siblings donors (n=3), and allogeneic
      bone marrow transplantation (n=5) or allo-PBSCT (n=1) from unrelated HLA matched
      donors. All patients received myeloablative regimens for eliminating residual
      leukemic cell. For aGVHD prophylaxis the patients with HLA-identical siblings
      donors received cyclosporine (CSA) alone, and the patients with mismatched
      siblings or unrelated donors received CSA, methotrexate, mycophenolate mofetil,
      and low-dose ATG. For inducing aGVHD after transplantation, patients were
      scheduled to be quickly reduced the maintenance dose of CSA at 20% to 30% off
      every week or treated with pre-emptive donor leukocyte infusion if there was no
      appearance of aGVHD at +30 days to 60 days after transplantation. RESULTS: After
      a median follow-up of 18.1 months, there were 24/30 (80%) patients developed
      aGVHD (grade 3 or 4 had 4/30, 13.3%). There were 11/19 (57.9%) patients developed
      chronic GVHD (cGVHD), with 3/19 (15.8%) had extensive cGVHD. Eighteen patients
      are alive with disease-free survival (18/30, 60%) and 12 patients have died of
      relapse (5/28, 17.9%) and TRM (7/30, 23.3%). CONCLUSION: Induction of aGVHD after
      transplantation is feasible and effective to prevent relapse in patients with
      refractory or relapsed acute leukemia.

PMID- 14693061
TI  - [Clinical study of single-dose G-CSF in mobilization and reconstruction of
      allogeneic peripheral blood stem cell transplantation].
AB  - BACKGROUND & OBJECTIVE: Mobilization of hematopoietic stem cells from healthy
      donors by stimulators such as granulocyte colony stimulating factor (G-CSF) in
      allogeneic peripheral blood stem cell transplantation (allo- PBSCT) is
      increasingly used clinically; however, the mechanism, the dose, and the schedule
      are not fully understood. This study was designed to evaluate the effectiveness
      and safety of single daily dose of 250 microg G-CSF (Lenograstim) for stem cell
      mobilization and hematopoietic reconstitution after allo-PBSCT. METHODS: The
      study included a group of 38 consecutive patients with hematological malignancies
      (acute leukemia:21 cases; chronic myelogenous leukemia:14 cases; myelodysplastic
      syndrome:3 cases) from January 2000 to June 2002. For the 38 sibling or matched
      unrelated donors G-CSF was administered at single daily dose of 250 microg
      despite of their body weight. Leukapheresis was performed on the fifth day. The
      patients were conditioned with total body irradiation (TBI)+cyclophosphamide or
      busulfan+cyclophosphamide. G-CSF support was given from the third day after stem
      cell reinfusion, usually until neutrophil recovery. RESULTS: The average dosage
      of G-CSF administrated was 4.8 microg x (kg x d)(-1). An average of 1.7 times of
      apheresis were performed. The median CD34(+) cell and CD34(+)/CD38(-) cell yield
      were 6.09 x 10(6)/kg and 1.33 x 10(6)/kg, respectively. The CD4(+)/CD8(+) ratio
      of the leukapheresis products was 1.41+/-0.51,and (17.61+/-6.64)% of the
      leukapheresis products were CD3(-)/CD16(+)CD56(+) cells. G-CSF was used after
      reinfusion for the median time of 9 days. The median time for WBC >1 x 10(9)/L,
      ANC >0.5 x 10(9)/L,and PLT >20 x 10(9)/L were 11,11,and 12 days, respectively.
      One patient died of severe infection on the fifth day after transplantation,
      while all the other patients achieved hematopoietic reconstitution satisfyingly.
      CONCLUSION: The administration of G-CSF in the single dose fashion in allo-PBSCT
      has a good effect in the mobilization of PBSC with minor side effects, and it can
      markedly promote hematopoietic reconstitution after transplantation.

PMID- 14693062
TI  - [Effect of modified FLAG regimen therapy on 33 patients with relapsed/refractory
      leukemia].
AB  - BACKGROUND & OBJECTIVE: The hematological complete remission (CR) rate of the
      FLAG regimen [fludarabine and cytarabine (Ara-C) and granulocyte-colony
      stimulating factor] for relapsed and refractory acute non- lymphocytic leukemia
      (ANLL) was 50-64%. The aim of this study was to investigate the modified FLAG
      regimen (Ara-C reduced to 200 mg per day intravenous injection for 5 to 7 days,
      and the patients were not administrated G-CSF before fludarabine and Ara-C) to
      examine whether it can achieve the same effectiveness and minor side effects.
      METHODS: Of 33 patients with acute leukemia, there were 16 cases with ANLL, 12
      cases with refractory acute lymphocytic leukemia (ALL) and 5 cases with relapsed
      ALL, respectively. All patients received fludarabine (Flu) 30 mg/m(2)/d
      intravenous injection for 5 days. And every patient received simultaneously Flu
      in combination with Ara-C intravenously for 5-7 days, 18 cases with Ara-C at a
      dose of 200 mg per day, 5 cases with Ara-c 500 mg/d and 10 cases with Ara-c 1000
      mg/d, respectively. One course consisted of 7 days. ALL patients and the patients
      received Ara-C at a dose of 200 mg per day were not treated with G-CSF before
      chemotherapy. ALL patients received vincristine at a dose of 2 mg/w for 2 times
      and prednisone 60-80 mg/d for 14 days. Of these 33 patients, the cases with white
      blood cell(WBC) counts less than 1.0 x 10(9)/L were treated with G-CSF at a dose
      of 300 microg/d subcutaneously until WBC counts were more than 3.0 x 10(9)/L. All
      patient were examined for bone marrow after every course. RESULTS: The CR rate of
      16 patients with refractory ANLL was 56.3%, whereas the CR rate of 12 cases with
      refractory ALL was 17% (P< 0.01). The CR rate of the patients with refractory
      ANLL who received Ara-C 200 mg/d was higher than those with refractory ANLL
      receiving Ara-C at the medial doses (70% versus 33%, P >0.05). The average
      durations of WBC< 0.6 x 10(9)/L and platelet< 15.6 x 10(9)/L were 5 days and 4.3
      days, respectively. Infection rate of the patients receiving Ara-C 200 mg/d was
      significantly lower than those receiving Ara-C at the medial doses (58% versus
      87.5%,P< 0.05). CONCLUSION: The CR rate of modified FLAG regimen is higher than
      classic FLAG, whereas the infection rate of the former is lower than the latter.

PMID- 14693063
TI  - [Preliminary study of lyophilized 10-hydroxycamptothecin in advanced or recurrent
      malignancies].
AB  - BACKGROUND & OBJECTIVE: 10-Hydroxycamptothecin (HCPT) is the inhibitor of
      topoisomerase I with anti-cancer effectiveness on several solid tumors. TUOXI
      (lyophilized HCPT) has higher purity and stability in comparison with solution
      for injection HCPT. The purpose of this study was to investigate the efficacy,
      toxicity, and proper dosage of TUOXI as single agent in treatment of advanced and
      recurrent solid tumors. METHODS: Sixty patients with the median age of 53 (range
      from 17 to 73 years) were enrolled into this multicenter phase II clinical trial.
      Among them, 18 patients were chemonaive and 42 were recurrent from chemotherapy;
      22 patients with NSCLC, 12 nasopharyngeal carcinoma, 9 primary liver cancer, 9
      colorectal carcinoma, 2 pancreatic carcinoma, and 6 miscellaneous malignancies.
      HCPT was given at the dosage of 6-8 mg/m(2) x d for 5-10 consecutive days based
      on the toxicity. RESULTS: Fifty-one patients were valuable for effectiveness. The
      objective response rate for the whole group was 15.7%. The partial remission (PR)
      rates were 16% for 6 mg/m(2) group and 15.4% for 8 mg/m(2) group, respectively.
      The PR rates were 13.7% (3/22) for NSCLC, 33.3% (3/9) for colorectal carcinoma,
      and 16.6% (2/12) for advanced nasopharyngeal carcinoma, respectively. The PR rate
      for 60 intent-to-treat patients was 13.3% (8/60). Myelosuppression was the dose
      limiting toxicity and other adverse reactions included nausea/vomiting, diarrhea,
      and skin rash. The incidence of grade III+IV adverse events were 32%, 8%, 8%, 6%,
      and 4% for leucopenia, skin rash, thrombocytopenia, nausea/vomiting, and
      diarrhea, respectively. No renal, pulmonary, and cardiac toxicity were found.
      CONCLUSION: TUOXI (HCPT lyophilized powder) had relatively broad- spectrum anti
      cancer efficacy and was effective on advanced or recurrent NCSLC, colorectal
      carcinoma, and NPC. And the recommended dosage is 6-8 mg/m(2) as 4 hours infusion
      for 5-10 consecutive days every 3 weeks. Further clinical investigation on large
      number of solid tumors cases are warranted.

PMID- 14693064
TI  - [Expression of P-glycoprotein and lung resistance protein in breast carcinoma and
      its relationship with prognosis].
AB  - BACKGROUND & OBJECTIVE: The multidrug resistance of tumor cells is the reason to
      failure of chemotherapy. The overexpression of P-glycoprotein (P-gp) and lung
      resistance protein (LRP) play important roles in the multidrug resistance of
      breast carcinoma. The objective of this study was to investigate the expression
      of P-gp and LRP in breast carcinoma and its relationship with prognosis. METHODS:
      Immunohistochemical assay with the LSAB immunostaining technique was used to
      determine protein expression of P-gp and LRP in the specimens of paraffin
      embedded tissues from 151 cases of breast carcinoma and 40 normal breast tissues
      (control). The results were evaluated on the basis of clinical pathological
      factors and the survival time of these cases. RESULTS: The expression of P-gp
      were found in 62 (40.8%) of the breast carcinoma samples and in 1 (2.5%) of
      control samples. The difference between the two groups was statistically
      significant (Chi(2)=21.27,P< 0.01). The expression of LRP were found in 121
      (80.1%) of the breast carcinoma samples and in 22 (55.0%) of control samples. The
      difference between the two groups was statistically significant (Chi(2)=10.62,P<
      0.01). The expression of P-gp were irrelative to age,tumor size,histotype,lymph
      nodes metastasis,tissue grading,clinical staging, ER condition,and prognosis. The
      expression of LRP were found in 62 (88.6%) of 70 cases with positive lymph nodes
      and 59 (72.8%) of 81 cases with negative lymph nodes. The difference between the
      two groups was statistically significant (Chi(2)=4.891, P< 0.05). The expression
      of P-gp were found in 55 (45.5%) of breast carcinomas with positive
      immunohistochemical reaction of LRP protein; while the expression of P-gp were
      found in 7(23.3%) of breast carcinomas with negative immunohistochemical reaction
      of LRP protein. The difference between the two groups was statistically
      significant (Chi(2)=3.990,P< 0.05). The expression of LRP were positively
      correlated with the lymph nodes metastases (r=0.197, P< 0.05) and the expression
      of P-gp (r=0.179,P< 0.05) and irrelative to age tumor size, histotype, lymph
      nodes metastases, tissue grading,clinical staging, and ER condition. Univariate
      analysis demonstrated worse disease-free survival in the patients with positive
      LRP than in those with negative LRP (Chi(2)=6.892,P< 0.01). Multivariate analysis
      of clinical and pathological data by Cox regression method did not demonstrated
      that both expression of P-gp and LRP were independent factors affecting the
      survival of breast carcinoma patients. CONCLUSION: The expression of P-gp and LRP
      have their characteristics and dissimilarity clinical significance in breast
      carcinoma tissues. The expression of LRP may correlate not only with MDR but also
      the lymph nodes metastases,prognosis and expression of P-gp in breast carcinoma
      tissues.

PMID- 14693065
TI  - [Evaluation of efficacy of treatment for 30 children with neuroblastoma].
AB  - BACKGROUND & OBJECTIVE: Neuroblastoma is one of common solid tumors in children.
      The major treatment modality for neuroblastoma (NB) is chemotherapy combined with
      operation or irradiation. But the survival rate is still low for advanced
      patients. Further study is needed for improving cure rate of neuroblastoma. This
      study was designed to evaluate the efficacy of children with neuroblastoma
      treated in Cancer Center, Sun Yat-sen University, and to explore reasonable
      therapy strategy. METHODS: The clinical data of 30 children with NB aged from 7
      months to 13 years were analyzed retrospectively. These patients were treated
      with chemotherapy plus operation or radiation. The stages were as follow: II,
      n=2; III, n=12; IV, n=15; IVS, n=1. Chemotherapy regimen was CAV
      (cyclophosphamide 750 mg/m(2) d1, vincristine 1.5 mg/m(2), d1, Adriamycin 50
      mg/m(2) d1) alternated with EP (teniposide or etoposide 60 mg/m(2) d1-d5,
      cisplatin 20 mg/m(2) d1-d5). The resection would be done after 4 to 6 cycles of
      chemotherapy if possible. The chemotherapy or radiation would be done after
      resection. If operation was not available, the patients continued to receive the
      chemotherapy. The patients with stage IVS only received cyclophosphamide plus
      vincristine. RESULTS: Among 30 patients, 2 cases achieved complete remission (CR
      6.7%) by chemotherapy alone; 21 cases achieved partial remission (PR 70%); 6
      cases showed no change (NC 20%); 1 cases showed progressive diseases (3.3%).
      Overall response rate (CR+PR) were 76.7% by chemotherapy alone. Of 21 PR
      patients, 9 cases could be resected;4 cases achieved CR after operation; 1 case
      achieved CR after radiation. The 2-year overall survival rate was 47.8% for all
      patients; 100% for Stage II/IVS, 34% for stage III, 22% for stage IV,
      respectively. Grade III/IV hematological toxicity occurred in 41.2% of the CAV
      regimen and 26.6% of the EP regimen. CONCLUSION: Chemotherapy plus operation or
      radiation is the major treatment for neuroblastoma. CAV/EP alternative
      chemotherapy is the active regimen for NB. The toxicity is tolerable. Advance
      stage NB needs further study for improving the prognosis.

PMID- 14693066
TI  - [Clinical results of advanced gastric cancer patients treated with oxaliplatin
      containing regimen].
AB  - BACKGROUND & OBJECTIVE: In vitro clinical research showed oxaliplatin (L-OHP)
      could obviously suppress the growth of gastric cancer cells in combination with
      most anti-cancer drugs and help these drugs to kill the tumor cells. This study
      was designed to evaluate the response and tolerance of oxaliplatin,leucovorin
      (LV), 5-fluorouracil (5-FU),and etoposide (VP-16) as first-line regimen in
      advanced gastric cancer, and compare with traditional chemotherapy regimen.
      METHODS: Forty-eight patients with advanced gastric cancer were divided into
      treatment group (L-OHP+LV+5-FU+VP-16) and control group(DDP+LV+5-FU+VP-16) using
      non-randomized method. L-OHP:135 mg/m(2), iv infusion 2 hours, d1(or DDP 20 mg,
      iv infusion, d1-5); LV:200 mg,iv infusion,d1-5; 5-FU:500 mg/m(2) CI 6 hours on d1
      5; VP-16: 100 mg, iv infusion d1-5. Every course lasted 3-4 weeks. RESULTS: The
      response rate was 64% (16/25) in treatment group (25 cases) and 34.8% (8/23) in
      control group (23 cases). The statistic difference was seen in two groups (P<
      0.05, Chi-square test). The median survival and 1-year survival rate were 11.5
      months and 45.6% for treatment group versus 10.5 months and 36.5% for control
      group. There was no statistical difference in two groups for overall survival (P
      >0.05, log-rank test). The main side effects were sensory neuritis in treatment
      group and nausea vomiting in control group. There were significant statistically
      differences in two groups (P< 0.05, Wilcoxon rank sum test). The other side
      effects were similar. CONCLUSION: L-OHP + VP-16 + LV + 5-FU regimen is effective
      and well tolerable for advanced gastric carcinoma.

PMID- 14693067
TI  - [Relationship of plasma concentration of 5-fluorouracil with toxicity and
      response in patients with nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Because there are several mechanisms of activity and
      toxicity and inter-individual variation in pharmaco- dynamics of 5-fluorouracil
      (5-FU),it is difficult to predict the sensitivity and toxicity of 5-FU in an
      individual patient. This study was designed to assess inter-patient variation of
      5-FU steady-state plasma concentration and the relationship of plasma
      concentration of 5-FU with toxic side effects and therapeutic response. METHODS:
      Twenty patients with nasopharyngeal carcinoma were treated with 5-FU combined
      with cisplatin(DDP). Blood samples were collected after 24 hours of infusion of 5
      FU. Plasma concentrations of 5-FU were measured using high performance liquid
      chromatography(HPLC) with column temperature at 25 Celsius degree, flow rate at
      1.3 ml/min, wave length at 260 nm and 1 mmol/l phosphate buffer (pH 3.0) as
      mobile phase. RESULTS: The plasma concentrations of 5-FU were normally
      distributed in the patients. No adverse effects were noted in the patients with
      plasma concentration of 5-FU lower than 600 microg/L, and severe toxic side
      effects were observed in the patients with plasma concentration of 5-FU greater
      than 1000 microg/L. The differences between plasma concentrations of 5-FU and
      each grade side effects reached statistical significance (P< 0.05). CONCLUSION:
      The plasma concentration of 5-FU have highly inter-individual variation in the
      patients with nasopharyngeal carcinoma. Plasma concentrations of 5-FU were
      associated with the toxicity and treatment response.

PMID- 14693068
TI  - [Chemosensitivity testing of topotecan as second-line agent in chemotherapy of
      ovarian cancer].
AB  - BACKGROUND & OBJECTIVE: The therapeutic principle of ovarian cancer was
      cytoreductive surgery assisting with chemotherapy. At present, cisplatin-based
      chemotherapy is the primary way for treatment of ovarian cancer. But most
      patients with advanced ovarian cancer were easy to recurrent and then become
      resistance to cisplatin. This study was designed to evaluate the clinical
      application of topotecan in recurrent ovarian cancer and ovarian cancer resistant
      to cisplatin. METHODS: An adenosine triphosphate chemosensitivity assay (ATP-CSA)
      was used to determine the drug sensitivity of 41 tissue specimens of fresh
      ovarian cancer. Cisplatin and topotecan were used as chemotherapeutic agents
      [1xPeak Plasma Concentration (PPC)], and then the results were analyzed. RESULTS:
      (1) In 41 specimens, the results showed that topotecan was more sensitive (80.5%)
      than cisplatin (51.2%). (2) In 20 cisplatin-resistance specimens, there were 18
      specimens sensitive to topotecan. CONCLUSIONS: Topotecan could be a kind of
      better second line drug in treating ovarian cancer, particularly when the patient
      was resistant to cisplatin.

PMID- 14693069
TI  - [Clinical adjuvant chemotherapy base on chemosensitivity in nude mouse subrenal
      capsule assay for non-small cell lung cancer].
AB  - BACKGROUND & OBJECTIVE: Chemotherapy is one of the main modalities for non-small
      cell lung cancer (NSCLC); however,survival period do not increase in this way
      even though good short-term response has been achieved. The aim of this study was
      to increase the survival period by postoperative adjuvant chemotherapy base on
      chemosensitivity testing in nude mouse subrenal capsule assay. METHODS: Fresh
      NSCLC specimens were transplanted into nude mouse subrenal capsule and 10 kinds
      of potential anticancer drugs were used in the vivo chemosensitivity test. One
      hundred and thirty patients with NSCLC undergone radical surgery were randomized
      into two groups: Group I (70 cases) and Group C (60 cases). The patients in Group
      I received adjuvant chemotherapy based on chemosensitivity testing in nude mouse
      assay. In Group C, 60 patients received adjuvant chemotherapy with standard
      regimen [cyclophosphamide (CTX) 600 mg/m(2) d1+Adriamycin (ADM) 40 mg/m(2) d1 +
      cisplatin (DDP) 20 mg/m(2) d1-5). RESULTS: The difference between two groups in
      local recurrence (43.1% versus 46%, P=0.556), metastasis (33.8% versus 34%,
      P=0.605), and 5-year survival rate (35.4% versus 34%,P=0.571) were not
      statistically significant. CONCLUSION: Adjuvant chemotherapy based on
      chemosensitivity testing in nude mouse subrenal capsule assay showed no
      significant improvement in long-term survival rate.

PMID- 14693070
TI  - [Research advances on function of promyelocytic leukemia (PML) protein].
AB  - Through reviewing research advances on promyelocytic leukemia(PML) protein at
      home and abroad in recent years, the authors summarized the biological functions
      of PML protein in this paper. Recent researches indicated that all PML protein
      isoforms have RBCC (Ring finger domain, B-box, Coiled-Coil domain, RBCC)or TRIM
      (TRIpartite motif). There was a close relationship between the three SUMO-1
      (small ubiquitin-related modifier, SUMO-1) modification site of PML protein and
      its location in nuclear bodies (NBs). Moreover, the location of PML protein in
      NBs is very important for the exertion of the function of PML protein and the
      formation of NBs. PML protein possesses multiple biological functions, such as
      intrinsic antiviral activities, suppressing the growth of tumor, participating in
      the differentiation of hemopoietic progenitor, regulating transcription of genes,
      inducing cell apoptosis, and so on. The PML gene haploinsufficiency and the
      formation of PML-RARalpha fusion protein are not only the pathogenesis of APL but
      also the target of treatment.

PMID- 14693071
TI  - [Anticancer effect of tanshinone and its mechanisms].
AB  - Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Salvia
      miltiorrhiza BUNGE, which is a traditional herbal medicine that is used to treat
      cardiovascular diseases. Recent studies showed that Tanshinone IIA possesses
      cytotoxic activity against many kinds of human carcinoma cell lines, induces
      differentiation and apoptosis and inhibits invasion and metastasis of cancer
      cells. Its mechanisms are thought as inhibiting DNA synthesis and proliferation
      of cancer cells, regulating the expression of genes related to proliferation,
      differentiation, and apoptosis, inhibiting the telomerase activity of cancer
      cells, and changing the expression of cellular surface antigen.

PMID- 14693073
TI  - The scope of the problem: physical symptoms of depression.

PMID- 14693074
TI  - A 4-step program for the diagnosis and management of depression.

PMID- 14693075
TI  - Depression and comorbid medical illness: therapeutic and diagnostic challenges.

PMID- 14693076
TI  - Applying neuropharmacy when treating patients with depression.

PMID- 14693077
TI  - From paper to patient: how do you translate science into clinical practice?

PMID- 14693078
TI  - Treatment regimens for managing depression in family practice.

PMID- 14693079
TI  - Response to treatment: gaining and maintaining remission from depression.

PMID- 14693080
TI  - Putting theory into practice: a challenging case study in the treatment of
      depression.

PMID- 14693081
TI  - EBA in evidence.

PMID- 14693082
TI  - Pseudomonas infections in the thermally injured patient.
AB  - Pseudomonas aeruginosa, remains a serious cause of infection and septic mortality
      in burn patients, particularly when nosocomially acquired. A prototypic burn
      patient who developed serious nosocomially acquired Pseudomonas infection is
      described as an index case which initiated investigations and measures taken to
      identify the source of the infection. The effect of changes in wound care to
      avoid further nosocomial infections was measured to provide data on outcome and
      cost of care. The bacteriology of Pseudomonas is reviewed to increase the burn
      care providers understanding of the behaviour of this very common and serious
      pathogen in the burn care setting, before reviewing the approach to detection of
      the organism and treatment both medically and surgically. After controlling the
      nosocomial spread of Pseudomonas in our burn unit, we investigated the morbidity
      and mortality associated with nosocomial infection with an aminoglycoside
      resistant Pseudomonas and the associated costs compared to a group of case
      matched control patients with similar severity of burn injury, that did not
      acquire resistant Pseudomonas during hospitalization at our institution. We found
      a significant increase in the mortality rate in the Pseudomonas group compared to
      controls. The morbidity in terms of length of stay, ventilator days, number of
      surgical procedures, and the amount of blood products used were all significantly
      higher in the Pseudomonas group compared to controls. Costs associated with
      antibiotic requirements were also significantly higher in the Pseudomonas group.
      Despite this increased resource consumption necessary to treat Pseudomonas
      infections, these efforts did not prevent significantly higher mortality rates
      when compared to control patients who avoided infection with the resistant
      organism. Thus, in addition to the specific measures required to identify and
      treat nosocomial Pseudomonas infections in burn patients, prevention of infection
      through modification of treatment protocols together with continuous infection
      control measures to afford early identification and eradication of nosocomial
      Pseudomonas infection are critical for cost-effective, successful burn care.

PMID- 14693083
TI  - Molecular epidemiology of Staphylococcus aureus colonization in a burn center.
AB  - The aim of this study was to investigate carriage of Staphylococcus aureus by
      patients and health care workers (HCW) and to define the genetic relationship of
      S. aureus strains isolated from burn wounds. At admission, 19/55 (34.5%) patients
      carried S. aureus in their nose and/or throat. Of this group, 95% subsequently
      colonized their burn wounds with S. aureus. Molecular analysis showed that in 78%
      of these cases the burn-wound colonizing strain was identical to the strain
      carried at admission. Importantly, 23/36 (64%) patients who did not carry S.
      aureus at admission also developed burn-wound colonization. In this group, three
      dominant genotypes were identified as colonizing strains of burn wounds. These
      clones represented also the majority (59%) of S. aureus strains cultured from the
      nose and/or throat of health care workers and patients. If patients were admitted
      to one of the Intensive Care rooms burn wounds of non-carriers were not colonized
      with S. aureus as long as they remained in such isolation. Only patients who
      carried S. aureus at admission developed burn-wound colonization with that
      genotype they carried in the nose or throat. Both carriage in patients and health
      care workers and auto-infection play a crucial role in (cross-) colonization
      events.

PMID- 14693084
TI  - An in vitro study of the anti-microbial efficacy of a 1% silver sulphadiazine and
      0.2% chlorhexidine digluconate cream, 1% silver sulphadiazine cream and a silver
      coated dressing.
AB  - Burn sepsis is a leading cause of mortality and morbidity in patients with major
      burns. The use of topical anti-microbial agents has helped improve the survival
      in these patients. There are a number of anti-microbials available, one of which,
      Silvazine (1% silver sulphadiazine (SSD) and 0.2% chlorhexidine digluconate), is
      used only in Australasia. No study, in vitro or clinical, had compared Silvazine
      with the new dressing Acticoat. This study compared the anti-microbial activity
      of Silvazine, Acticoat and 1% silver sulphadiazine (Flamazine) against eight
      common burn wound pathogens. METHODS: Each organism was prepared as a suspension.
      A 10 microl inoculum of the chosen bacterial isolate (representing approximately
      between 10(4) and 10(5) total bacteria) was added to each of four vials, followed
      by samples of each dressing and a control. The broths were then incubated and 10
      microl loops removed at specified intervals and transferred onto Horse Blood
      Agar. These plates were then incubated for 18 hours and a colony count was
      performed. RESULTS: The data demonstrates that the combination of 1% SSD and 0.2%
      chlorhexidine digluconate (Silvazine) results in the most effective killing of
      all bacteria. SSD and Acticoat had similar efficacies against a number of
      isolates, but Acticoat seemed only bacteriostatic against E. faecalis and
      methicillin-resistant Staphylococcus aureus. Viable quantities of Enterobacter
      cloacae and Proteus mirabilis remained at 24h. CONCLUSION: The combination of 1%
      SSD and 0.2% chlorhexidine digluconate (Silvazine) is a more effective anti
      microbial against a number of burn wound pathogens in this in vitro study. A
      clinical study of its in vivo anti-microbial efficacy is required.

PMID- 14693085
TI  - An evaluation of the role of systemic antibiotic prophylaxis in the control of
      burn wound infection at the Lagos University Teaching Hospital.
AB  - A prospective study was carried out on 61 patients to evaluate the role of
      systemic antibiotic prophylaxis in the control of burn wound infection. The
      patients were randomised into three groups: group 1 (n=21) received ampicillin
      and cloxacillin; group 2 (n=20) received erythromycin and genticin and a control
      group (n=20) received no systemic chemo prophylaxis. The burn wounds were
      similarly managed. Wound colonisation was determined from surface wound swab
      cultures and wound infection was determined from wound biopsy cultures and
      histopathology. The colonisation time (days) for the groups was 2.90+/-0.92,
      3.15+/-0.77 and 3.05+/-0.83 for groups 1 and 2 and the control, respectively. The
      commonest organism isolated from contaminated wounds was Staphylococcus aureus.
      Wound infection was established in 5.70+/-1.70, 5.75+/-1.62 and 5.6+/-1.90 days
      for group 1, group 2 and the control group, respectively. There was no
      significant difference between wound infection time of control and group 1 nor
      was there such difference between the control and group 2 (P>0.05). The commonest
      organism infecting burn wounds in all the groups was Pseudomonas aeruginosa
      followed by S. aureus. There was however a significant difference between the
      treatment groups and the control (P<0.05) with regard to the percentage of
      infected wounds that grew P. aeruginosa, compared to those that grew S. aureus.
      It was concluded that systemic antibiotic prophylaxis is of no value in
      controlling burn wound sepsis, and might even favour the growth of P. aeruginosa
      in the burn wounds.

PMID- 14693086
TI  - Reflections on rehabilitation: the AB Wallace lecture to the British Burn
      Association April 2003.

PMID- 14693087
TI  - Nerve quantification in female red Duroc pig (FRDP) scar compared to human
      hypertrophic scar.
AB  - A significant impediment to studying hypertrophic scar is the lack of an animal
      model. We have confirmed similarities between scarring in the female red Duroc
      pig (FRDP) and human hypertrophic scar and conclude that this model warrants
      validation. Reports have suggested that the cutaneous nervous system may play a
      role in hypertrophic scar development and several studies have shown nerve
      density in hypertrophic scar to be increased. The purpose of this study was to
      further validate the FRDP model of hypertrophic scar by quantifying nerves in
      FRDP tissue and comparing the findings to human hypertrophic scar. Wounds of
      varying depth were created on the backs of two FRDP and tissue samples were
      harvested at 10 days, 1 month and 5 months post-wounding. Human specimens were
      obtained from six burn patients. Immunohistochemistry was performed and digital
      images were captured. Color subtractive computer-assisted image analysis was used
      to quantify nerve density and nerve area fraction. The results demonstrate that
      nerve tissue is increased in FRDP scar tissue and is quite similar to that in
      human hypertrophic scar and to that described in the literature. These data
      provide additional evidence that the FRDP model may be useful for studying
      hypertrophic scarring.

PMID- 14693088
TI  - The effects of inhaled nitric oxide on cardiac pathology and energy metabolism in
      a canine model of smoke inhalation injury.
AB  - OBJECTIVE: The effects of inhaled nitric oxide (NO) on cardiac pathology and
      energy metabolism were studied in a canine model of smoke inhalation injury.
      MATERIAL AND METHOD: Twenty-one dogs were randomly divided into three groups:
      four dogs constituted the normal control group (group N), eight dogs subjected to
      smoke inhalation followed by O(2) inhalation (FiO(2)=0.45) constituted the injury
      control group (group C), and nine dogs inhaling a mixture of O(2) and 45ppm
      nitric oxide after smoke exposure served as the treatment group (group T).
      Myocardial zymograms were continuously measured, and ventricular muscles were
      examined for histopathology in the end of the experiment. RESULTS: Lactate
      dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (alpha-HBD), creatine
      kinase (CK) and glutamic oxalacetic transaminase (GOT) in group T were less than
      those in group C(P<0.05, or P<0.01). ATP content and energy charge (EC) in group
      T were higher significantly than those in group C(P<0.01). Light microscopy and
      electron microscopy indicated that the ventricular pathologic changes in group T
      were milder than in control group. CONCLUSION: Nitric oxide inhalation relieved
      myocardial damage and improved energy metabolism.

PMID- 14693089
TI  - Influence of demographics and inhalation injury on burn mortality in children.
AB  - BACKGROUND: Pulmonary failure has emerged as one of the leading causes of
      mortality in burned children due, in part, to the success in reducing the
      incidence of sepsis, early surgery and fluid resuscitation, and new advances in
      nutritional support. To evaluate the effect of pulmonary injury, age, gender,
      race, and burn size on mortality, the records of 3179 burned children admitted to
      our burn center from 1985 to 2001 were reviewed. In this population, 1246 were
      admitted within 14 days of injury with burns greater than 20% of their total body
      surface area (TBSA). METHODS: Lethal burn areas (LAs) for a thermal injury only
      or burn plus inhalation injury were estimated from best fit probit curve within
      95% confidence limits. Data analysis was by chi(2)-test, t-test, or Fisher's
      exact test where appropriate. RESULTS: The lethal burn area for a 10% mortality
      rate with and without concomitant inhalation injury was a 50 and 73% TBSA burn,
      respectively. Children up to the age of 3 with >/=20% TBSA burns had a higher
      rate of mortality (9.9%) compared to those 3-12 years of age (4.9%) and 13-18
      years of age (4.2%). Children with 21-80% TBSA burns showed a significant
      difference in mortality (P<0.05) between those with burn plus inhalation injury
      (13.9%) and burn only (2.9%), while those with 81-100% TBSA burns showed no
      significant difference between burn only and burn plus inhalation injury.
      CONCLUSION: Inhalation injury remains one of the primary contributors to burn
      mortality. Children under the age of 3 years, however, are at a higher risk both
      with and without inhalation injury.

PMID- 14693090
TI  - Acid burns from personal assault in Uganda.
AB  - Acid burns from assault represent a substantial and neglected proportion of burn
      injuries in the developing world. A retrospective chart review was conducted to
      assess the frequency of acid burns in relation to total burns requiring admission
      in Kampala, Uganda. Seventeen percent of the adult burns admitted at New Mulago
      hospital over an 18-month period resulted from acid assault. Patients had a mean
      age of 33.1 years, with a male to female ratio of 1.1:1. The average extent of
      injury was 14.1% total body surface area (TBSA), commonly involving the face
      (86.7%), head and neck (66.7%), upper limbs (60.0%) and chest (53.3%). Thirty
      three percent of patients suffered partial or complete blindness. Mean length of
      stay in hospital was 49.5 days and all patients survived. Patterns of assault
      followed two common trends: attacks during robberies (46.7%), and attacks
      associated with domestic disputes (33.3%). The Ugandan pattern is contrasted with
      patterns reported from Bangladesh, Cambodia and Jamaica with a view to
      understanding the social context underlying such assaults. Prevention of these
      hideous injuries will require further understanding of their underlying social
      and cultural determinants. Serious questions remain whether public education
      programs will reduce the incidence of acid assault or increase it by giving
      potential assailants an idea they did not have before.

PMID- 14693091
TI  - Reduced hospitalisation of burns patients following a multi-media campaign that
      increased adequacy of first aid treatment.
AB  - CONTEXT: Concern engendered by a previous study that showed inadequate first aid
      for burn injuries was prevalent in the community led to a novel multi-media
      public health campaign ensued to address the issue. OBJECTIVE: To determine
      whether this public health campaign influenced behaviour by altering first aid
      treatment for burn injuries (BFAT). DESIGN, SETTING AND POPULATION: Prospective
      intervention study. Consecutive patients with acute burn injuries over two 4
      month intervals, presenting to a regional burn service, Auckland, New Zealand.
      This research was ethically approved by the Local Research Ethics Committee. MAIN
      OUTCOME MEASURES: Demographics, burn size, adequacy of burn first aid,
      outpatient/inpatient wound care and operative intervention requirement. RESULTS:
      Adequacy of BFAT improved following the campaign (59% versus 40%, P=0.004). Fewer
      inpatient admissions (64.4% versus 35.8%, P<0.001) and surgical procedures (25.6%
      versus 11.4%, P<0.001) were undertaken following the campaign with a
      corresponding increase in outpatient care. Greatest decreases were observed in
      Maori and Pacific Islanders, and in children <10 years old. CONCLUSIONS: Adequacy
      of BFAT together with a reduction in the numbers of patients requiring inpatient
      surgical care was improved by a multi-media public awareness campaign.

PMID- 14693092
TI  - White spirit--paint thinner, skin stripper.

PMID- 14693093
TI  - Don't miss HIT (heparin induced thrombocytopenia).
AB  - Thrombocytopenia following a burn injury can cause serious complications. There
      are several possible causes including the burn itself, drugs, sepsis and
      disseminated intravascular coagulation (DIC). A case report of a patient who
      developed heparin induced thrombocytopenia (HIT) whilst on haemofiltration for
      acute renal failure is presented. The aetiology of thrombocytopenia in a burns
      patient and its management is discussed. The key to effective treatment of
      thrombocytopenia is identification of the cause. HIT is an important diagnosis to
      include in the differential.

PMID- 14693094
TI  - The relation between social deprivation and incidence of burns in an A&E setting.

PMID- 14693095
TI  - Oral fluid resuscitation.

PMID- 14693096
TI  - Vote "yes" for stem cells.

PMID- 14693097
TI  - Cocaine use may damage dopaminergic system.

PMID- 14693098
TI  - Stroke: prediction, prevention, and outcome.

PMID- 14693099
TI  - Multiple sclerosis: disease markers accelerate progress.

PMID- 14693100
TI  - Epilepsy: major advances in treatment.

PMID- 14693101
TI  - Important advances in headache.

PMID- 14693102
TI  - Neurological infection.

PMID- 14693103
TI  - Neuro-oncology: diagnosis in the spotlight.

PMID- 14693104
TI  - Movement disorders: Parkinson's disease dominates.

PMID- 14693105
TI  - Genes, trials, and care: the dynamics of neuromuscular disease.

PMID- 14693106
TI  - Evolutionary rather than revolutionary progress in dementia.

PMID- 14693107
TI  - Paediatric neurology: genes and the environment.

PMID- 14693108
TI  - Dementia with Lewy bodies.
AB  - Dementia with Lewy bodies (DLB) is the second commonest cause of
      neurodegenerative dementia in older people. It is part of the range of clinical
      presentations that share a neuritic pathology based on abnormal aggregation of
      the synaptic protein alpha-synuclein. DLB has many of the clinical and
      pathological characteristics of the dementia that occurs during the course of
      Parkinson's disease. Here we review the current state of scientific knowledge on
      DLB. Accurate identification of patients is important because they have specific
      symptoms, impairments, and functional disabilities that differ from those of
      other common types of dementia. Severe neuroleptic sensitivity reactions are
      associated with significantly increased morbidity and mortality. Treatment with
      cholinesterase inhibitors is well tolerated by most patients and substantially
      improves cognitive and neuropsychiatric symptoms. Clear guidance on the
      management of DLB is urgently needed. Virtually unrecognised 20 years ago, DLB
      could within this decade be one of the most treatable neurodegenerative disorders
      of late life.

PMID- 14693109
TI  - Malformations of cortical development: burdens and insights from important causes
      of human epilepsy.
AB  - Malformations of cortical development (MCD) are important causes of chronic
      epilepsy in human beings. A blanket term, MCD encompasses many varied
      developmental disorders with diverse clinical manifestations in patients that
      neurologists, paediatricians, and learning disability psychiatrists will
      encounter. Advances in imaging and genetics have led to a significant increase in
      our understanding of MCD, which has in turn enriched our knowledge of human
      epileptogenesis and normal brain development and function. In this review, I
      discuss some of the most common or enlightening MCD: focal cortical dysplasia,
      periventricular heterotopia, polymicrogyria, band heterotopia and lissencephaly,
      dysembryoplastic neuroepithelial tumours, and microdysgenesis. Clinical and
      imaging features, genetic aetiologies, treatments, and the insights that have
      resulted from MCD study are covered. The burden of epilepsy due to MCD is
      significant and there is still much to learn about MCD.

PMID- 14693110
TI  - Diffusion-weighted MRI for the "small stuff": the details of acute cerebral
      ischaemia.
AB  - Diffusion-weighted MRI (DWI) has already had a substantial effect on the
      diagnosis of patients with ischaemic stroke. It provides in vivo pathological
      information and allows the differentiation of acute stroke from chronic stroke
      and from non-specific white-matter lesions. The high contrast of the acute DWI
      lesion against the dark background facilitates the detection of lesions even when
      they are 1 mm or less in diameter. Small lesions, which are undetectable by other
      means, include small lacunar infarcts, punctate cortical infarcts, and DWI bright
      dots in patients with transient ischaemic attacks (TIA). The latter constitute
      remnants or "footprints" of recent ischaemia and confirm the clinical TIA
      syndrome as ischaemic. Because of these attributes, DWI not only confirms the
      clinical diagnosis, but also facilitates the recognition of certain patterns of
      ischaemia, thereby providing clues to the underlying aetiology. DWI is becoming
      an important technique for optimum management of patients.

PMID- 14693111
TI  - Antimuscarinics for treatment of overactive bladder.
AB  - For many years, antimuscarinic drugs have been the first-line pharmacological
      treatment for urgency, frequency, and urge incontinence, all symptoms of the
      disorder termed overactive bladder. Antimuscarinic treatment is not always
      effective and is associated with side-effects that limit its clinical use. The
      clinical significance of the effects of antimuscarinic drugs has been questioned
      lately. In this review, the rationale for the use of these drugs in the
      management of overactive bladder is re-examined and the results of treatment are
      discussed. I conclude that these drugs are the only treatment with undisputed
      effectiveness in the treatment of overactive bladder. They may not be the perfect
      treatment for all patients with this disorder, but their value for individual
      patients should not be underestimated. Further clinical trials with improvement
      in quality of life as the primary endpoint are needed and may give a fair
      reflection of the clinical value of antimuscarinic drugs.

PMID- 14693112
TI  - Adjunctive dexamethasone treatment in acute bacterial meningitis.
AB  - The initiation of antibiotic treatment on suspicion of bacterial meningitis is
      important, but it is not enough to improve the prognosis for patients, especially
      those with pneumococcal meningitis. The mortality and morbidity of pneumococcal
      meningitis are still devastating, and results of a recent randomised trial have
      shown evidence in favour of dexamethasone treatment given before or with the
      first antibiotic dose. Adjuvant dexamethasone is unequivocally recommended in
      children and adults with haemophilus meningitis or pneumococcal meningitis. The
      benefit of adjunctive dexamethasone is likely to be greatest in patients who are
      otherwise healthy and present early with acute bacterial meningitis.
      Dexamethasone is not currently recommended for the treatment of gram-negative
      bacillary meningitis and neonatal meningitis. Dexamethasone, before or with the
      first dose of antibiotic, is likely to be one of the most significant practice
      changes that will benefit many adults and children with common types of acute
      bacterial meningitis and has been of proven value in the developed world.

PMID- 14693113
TI  - A 46-year-old man with numbness and shock-like sensations in hands, feet, and
      jaw.

PMID- 14693117
TI  - Does size matter?

PMID- 14693118
TI  - Experimental porcine rubulavirus (La Piedad-Michoacan virus) infection in
      pregnant gilts.
AB  - Porcine rubulavirus (La Piedad-Michoacan virus) (PoRV-LPMV) is a member of the
      Paramyxoviridae family that causes encephalitis in young piglets and infertility
      in adult sows and boars. Infertility in sows naturally infected by PoRV-LPMV is
      characterized by an increased number of returns to oestrus, stillbirths and
      mummified fetuses. In this study, nine seronegative gilts were inoculated
      intranasally with the PAC-3 strain of PoRV-LPMV at week 6 or 10 of gestation.
      These animals were then killed at weeks 8 or 15 of gestation (seven gilts) or
      after natural parturition (two gilts). Four control gilts were mock-infected at
      gestation week 6 or 10 and killed between 2 and 4 weeks later. Gross lesions of
      focal congestion and haemorrhage were seen in the placenta and endometrium of one
      gilt infected at gestation week 6 and one infected at gestation week 10. PoRV
      LPMV was isolated, at 2-6 weeks post-inoculation (pi), from lung, tonsils, ovary,
      placenta, uterus and lymph nodes of three of the gilts infected at gestation week
      6 and at 2-3 weeks pi from lung, tonsil and ovary of two gilts infected at
      gestation week 10. Many of the fetuses of eight infected gilts were smaller than
      normal and had dermal ecchymoses. Dehydrated or mummified fetuses were present in
      six of the infected gilts but not in any control animal. PoRV-LPMV was isolated
      from brain, lung and liver of fetuses from two gilts infected at gestation week
      6, and from two infected at gestation week 10. These results indicate that, after
      experimental infection, PoRV can replicate in tissues of seronegative pregnant
      gilts, cross the placenta, and cause fetal death and mummification.

PMID- 14693119
TI  - Histological and immunohistochemical study of clinically normal skin of
      Leishmania infantum-infected dogs.
AB  - Skin lesions are the most usual manifestation of canine leishmaniosis. The aim of
      this study was to investigate the histological pattern and parasite load in
      clinically normal skin of Leishmania-infected dogs. Two groups of Leishmania
      infected dogs were studied. Group A consisted of 15 symptomless animals which,
      although seronegative or only mildly seropositive, gave a positive polymerase
      chain reaction (PCR) for Leishmania in the skin. Group B consisted of 20
      clinically affected dogs which were highly seropositive and PCR-positive.
      Biopsies of normal skin from all dogs were processed for routine histology and
      Leishmania immunohistochemistry. The study demonstrated microscopical lesions and
      the presence of parasites in the skin from dogs of group B, but not group A. The
      results cast doubt on the relevance of infected but symptomless dogs in the
      epidemiology of canine leishmaniosis. In contrast, however, the clinically normal
      skin of sick dogs harbours the parasite and probably plays a role in the
      transmission of leishmaniosis.

PMID- 14693120
TI  - P-cadherin expression in canine mammary tissues.
AB  - P-cadherin is a classical cadherin expressed by myoepithelial cells in mammary
      tissue. Its expression in human breast cancer has been associated with aggressive
      tumour behaviour. To analyse the possible role of P-cadherin in canine mammary
      carcinogenesis, its expression was examined immunohistochemically in 82 samples
      of normal (n=2), hyperplastic (n=11) and neoplastic (n=69) canine mammary
      tissues. In normal and hyperplastic canine mammary glands, P-cadherin was
      restricted to myoepithelial cells, usually at sites of cell-to-cell contact. In
      tumour tissues, however, P-cadherin expression was observed in both epithelial
      and myoepithelial cells, with a cytoplasmic pattern of cellular distribution.
      Aberrant epithelial P-cadherin immunolabelling was found in 19/44 (43%) benign
      tumours and in 16/25 (64%) malignant tumours (P<0.001). In malignant tumours, a
      significant correlation between P-cadherin expression intensity and histological
      type was observed (P<0.05).

PMID- 14693121
TI  - Molybdenum-associated pituitary endocrinopathy in sheep treated with ammonium
      tetrathiomolybdate.
AB  - Ammonium tetrathiomolybdate (TTM) has hitherto been the treatment of choice for
      chronic copper poisoning in sheep, but the long-term consequences have not been
      evaluated. This study was based on a flock of copper-poisoned sheep which, after
      apparently successful treatment with TTM, became infertile and progressively
      unthrifty and eventually died 2-3 years later. The last five surviving animals
      were subjected to euthanasia and detailed study. Necropsy revealed marked wasting
      together with depletion of the pituitary and adrenal glands, testicular atrophy
      and ovarian cystic follicles. Histopathological examination revealed a non
      inflammatory atrophy or degeneration of the adenohypophysis with loss of trophic
      cells; adrenocortical and testicular atrophy and ovarian degeneration. The
      regressive changes in the anterior lobe of the pituitary were confirmed by
      immunocytochemical labelling, which revealed a marked depletion of
      adrenocorticotrophic hormone (ACTH), follicle stimulating hormone (FSH) and
      luteinizing hormone (LH) in the affected pituitaries by comparison with healthy
      controls. Excess molybdenum (Mo) retention (P<0.02) was identified by inductively
      coupled plasma mass spectrometry (ICPMS) in the pituitaries and atomic absorption
      spectrometry (AAS) in the adrenals and brains of affected sheep. It was concluded
      that molybdenum introduced systemically as TTM is retained within the brain,
      pituitary and adrenal glands and is associated with a toxic endocrinopathy. It is
      postulated that Mo administered as thiomolybdate adversely affects the
      hypothalamo-adenohypophyseal system by interfering with trophic hormone release,
      leading to the cessation of reproductive activity and ultimately the failure of
      intermediary metabolism. Whether Mo exerts its effect centrally or directly on
      the pituitary was not established.

PMID- 14693122
TI  - Immunohistochemical detection of macrophages in the short-finned pilot whale
      (Globicephala macrorhynchus) and Risso's dolphin (Grampus griseus).
AB  - Macrophages play a central role in the immune system, but few markers are
      available for their detection in cetaceans. The purpose of the present study,
      therefore, was to examine the cross-reactivity for two cetacean species (short
      finned pilot whale and Risso's dolphin) of four anti-human antibodies (SRA-E5, AM
      3K, EBM11 and anti-human lysozyme). The distribution of SRA-E5- and AM-3K
      positive cells was similar, both antibodies labelling (1) many resident
      macrophages in the spleen, lymph nodes, liver, lung, kidney, intestine and
      dermis, and (2) exudate macrophages in the hepatic interlobular septa. Anti-human
      lysozyme antibody also labelled both resident and exudate macrophages. However,
      double immunohistochemistry showed that the majority of AM-3K-positive cells in
      the spleen and liver were also labelled by SRA-E5; on the other hand, anti-human
      lysozyme-positive cells did not always correspond with AM-3K-positive cells.
      Cetacean tissues contained no EBM11-positive cells. The study demonstrated the
      potential values of SRA-E5, AM-3K and anti-human lysozyme antibody for cetacean
      macrophage studies.

PMID- 14693123
TI  - Decreased expression of equine herpesvirus-1 early and late genes in the placenta
      of naturally aborted equine fetuses.
AB  - Intrauterine infection with equine herpesvirus-1 (EHV-1) has been considered to
      be the consequence of transplacental transmission of the virus following maternal
      cell-associated viraemia. In this study the state of EHV-1 gene expression in the
      placenta of seven naturally aborted equine fetuses was examined. Neither lesions
      nor viral antigens were detected in the placenta of the fetuses. The amount of
      infectious virus in the placentas was considerably lower than that in the fetal
      lungs, which showed pneumonia and typical herpesvirus inclusions. Quantitative
      dot blot hybridization with probes specific for immediate-early (IE), early
      (ICP0), and late (gD and gK) genes revealed that the placentas expressed the IE
      gene at a level comparable with that in the lungs; however, expression of the
      ICP0, gD and gK genes was significantly weaker in the placentas than in the
      lungs. In-situ hybridization demonstrated that both IE and gK RNAs were
      distributed mainly in the cytoplasm of trophoblasts. These results suggest that
      the low level of early and late gene transcription may be related to the limited
      production of viral progeny and the lack of immunoreactivity for viral antigen in
      trophoblasts infected with EHV-1.

PMID- 14693124
TI  - Natural killer (NK) cells play a critical role in the early innate immune
      response to Chlamydophila abortus infection in mice.
AB  - Chlamydophila abortus, the aetiological agent of ovine enzootic abortion, induces
      a strong inflammatory reaction that leads to the T helper cell (Th1) specific
      immune response necessary for the clearance of infection. Because the role of
      natural killer (NK) cells during the first stages of this response has received
      little attention, this study focused on determining the function of these cells
      in a mouse model of infection. The location of NK cells in the liver and spleen
      of infected mice was examined immunohistochemically with an anti-Ly49G monoclonal
      antibody. The number of NK cells increased during the infection both in spleen
      and liver. In subsequent experiments, an anti-asialo GM1 polyclonal antibody was
      injected to deplete the NK cells. NK-depleted mice showed a substantial increase
      in their susceptibility to C. abortus infection, with high mortality rates and an
      increased burden of bacteria in the liver. Histopathological studies showed that
      inflammatory foci, composed mainly of neutrophils, were greater in size and
      number in depleted mice, while numerous chlamydial inclusions were associated
      with the foci. Serum concentrations of IFN-gamma, a key cytokine in the control
      of C. abortus infection, were substantially reduced in the NK-depleted mice. To
      establish the relationship between NK cells and other components of the innate
      immune response, neutrophils were depleted with the RB6-8C5 antibody. These cells
      were shown to be crucial in the recruitment of NK cells to the inflammatory foci.

PMID- 14693125
TI  - Neurotropism of swine haemagglutinating encephalomyelitis virus (coronavirus) in
      mice depending upon host age and route of infection.
AB  - Mice aged 1, 4 or 8 weeks were inoculated with haemagglutinating
      encephalomyelitis virus (HEV), strain 67N, by the intracerebral (i.c.),
      intranasal (i.n.), intraperitoneal (i.p.), subcutaneous (s.c.), intravenous
      (i.v.) or oral route, with different doses. In 1-week-old mice, mortality and
      mean time to death were mostly the same regardless of the inoculation route,
      except for the oral route, which appeared to be the least effective. The virus
      killed 4-week-old mice readily by all routes of inoculation except the oral, and
      8-week-old mice by i.c., i.n. or s.c. inoculation. In descending order of
      efficacy, the routes of HEV infection were: i.c., i.n., s.c., i.p., i.v. and
      oral. To follow the spread of HEV from peripheral nerves to the central nervous
      system (CNS), the virus was inoculated subcutaneously into the right hind leg of
      4-week-old mice. The virus was first detected in the spinal cord on day 2, and in
      the brain on day 3. The brain titres became higher than those of the spinal cord,
      reaching a maximum of 10(7)PFU/0.2 g when the animals were showing CNS signs.
      Viral antigen was first detected immunohistochemically in the lumbar spinal cord
      and the dorsal root ganglion ipsilateral to the inoculated leg; it was detected
      later in the pyramidal cells of the hippocampus and cerebral cortex, and in the
      Purkinje cells of the cerebellum but not in the ependymal cells, choroid plexus
      cells or other glial cells. The infected neurons showed no cytopathological
      changes.

PMID- 14693126
TI  - Smooth muscle hamartoma of the abomasum in a calf.
AB  - This report describes a case of smooth muscle hamartoma of the abomasum in a 6
      month-old steer humanely killed because of severe pneumonia. At necropsy, marked
      thickening of the abomasal wall in the area of the pylorus was found. On cut
      section, the thickness of the submucosal layer, extending from the submucosa to
      the muscularis propria, was seen to be increased to 3 cm. The upper (i.e.,
      nearest to the gut lumen) half of the sectioned thickening was composed mainly of
      adipose-like tissue and the lower half mainly of muscle-like tissue.
      Histologically, the submucosal layer was composed of fibroadipose tissue, within
      which were embedded, to varying degrees, numerous well-defined, haphazardly
      oriented, thin to thick bundles of smooth muscle fibres. This appears to be the
      first report of smooth muscle hamartoma of the stomach or abomasum in animals,
      including man.

PMID- 14693127
TI  - Experimentally induced teat stenosis in dairy ewes: clinical, pathological and
      ultrasonographic features.
AB  - A strain of Staphylococcus chromogenes was introduced into the teat cistern of
      five ewes, teat inflammation and stenosis being the primary consequences.
      Initially, the inoculated teats were swollen and warm; later, a hard structure
      was palpated running lengthwise inside the teat, with a thick ring above the tip
      of the teat, which interfered with expression of milk. Mastitis, confirmed by
      clinical, cytological, bacteriological and histological findings, was evident 4
      days after infection. Ultrasonographically, a hyperechoic line under the mucosa
      of the teat cistern was observed. At necropsy, the duct wall of the inoculated
      teats was found to be thickened. Histopathological features included leucocytic
      infiltration, especially under the mucosa of the teat, and extensive fibrosis in
      the subcutaneous tissues. S. chromogenes was recovered from scrapings from the
      duct and the cistern of the inoculated teats.

PMID- 14693128
TI  - Arterionecrosis of the equine mesentery in naturally occurring endotoxaemia.
AB  - This report describes the mesenteric arteriolar lesions in a Thoroughbred
      racehorse with endotoxaemia due to colic. The vascular lesions consisted of a
      striking loss of medial smooth muscle cells, associated with granular cell debris
      derived from necrosed muscle cells, plasma insudation, erythrocyte infiltration
      and the deposition of a fibrinoid substance (fibrinoid degeneration) in the
      entire arterial wall, possibly produced by the infiltration of blood components
      through endothelial cell junctions into the arterial wall. The morphology of the
      mesenteric arteriolar necrosis closely resembled that seen in experimental equine
      endotoxaemia and in horses that died from colic; it also resembled that of Shiga
      toxin-induced arteriolar lesions in oedema disease of swine and of the
      arterionecrosis in human cerebral arteries that may lead to hypertensive
      intracerebral haemorrhage.

PMID- 14693129
TI  - Adsorption of Cr(VI) and Se(IV) from their aqueous solutions onto Zr4+
      substituted ZnAl/MgAl-layered double hydroxides: effect of Zr4+ substitution in
      the layer.
AB  - Hydrotalcite-like compounds (layered double hydroxides, LDHs) containing varying
      amounts of Al(3+), Zr(4+), and Zn(2+) or Mg(2+) in the metal hydroxide layer have
      been synthesized and characterized by various physicochemical methods. The
      adsorption behavior of uncalcined (as-synthesized) and calcined LDHs have been
      investigated for Cr(2)O(7)(2-) and SeO(3)(2-). The mixed oxides, obtained on
      calcination at 450 degrees C, exhibit high adsorption capacities for Cr(2)O(7)(2
      ) (1.6-2.7 meq/g) and SeO(3)(2-) (1.1-1.5 meq/g), where adsorption occurs through
      rehydration. Substitution of Zr(4+) in the LDHs, for either M(2+) or Al(3+) ions,
      increases the adsorption capacity up to 20%, thus providing an alternative way to
      enhance the adsorption capacity of this type of material. The high adsorption
      capacity of these materials could be successfully used for removal of undesirable
      anions from water and also for synthesis of intercalated materials with tailored
      acidobasicity.

PMID- 14693130
TI  - EXAFS study of mercury(II) sorption to Fe- and Al-(hydr)oxides. II. Effects of
      chloride and sulfate.
AB  - Common complexing ligands such as chloride and sulfate can significantly impact
      the sorption of Hg(II) to particle surfaces in aqueous environmental systems. To
      examine the effects of these ligands on Hg(II) sorption to mineral sorbents,
      macroscopic Hg(II) uptake measurements were conducted at pH 6 and [Hg](i)=0.5 mM
      on goethite (alpha-FeOOH), gamma-alumina (gamma-Al(2)O(3)), and bayerite (beta
      Al(OH)(3)) in the presence of chloride or sulfate, and the sorption products were
      characterized by extended X-ray absorption fine structure (EXAFS) spectroscopy.
      The presence of chloride resulted in reduced uptake of Hg(II) on all three
      substrates over the Cl(-) concentration ([Cl(-)]) range 10(-5) to 10(-2) M,
      lowering Hg surface coverages on goethite, gamma-alumina, and bayerite from 0.42
      to 0.07 micromol/m(2), 0.06 to 0.006 micromol/m(2), and 0.55 to 0.39
      micromol/m(2) ([Cl(-)]=10(-5) to 10(-3) M only), respectively. This reduction in
      Hg(II) uptake is primarily a result of the formation of stable, nonsorbing
      aqueous HgCl(2) complexes in solution, limiting the amount of free Hg(II)
      available to sorb. At higher [Cl(-)] beam reduction of Hg(II) to Hg(I) was
      observed, resulting in the possible formation of aqueous Hg(2)Cl(2) species and
      the precipitation of calomel, Hg(2)Cl(2(s)). The presence of sulfate caused
      enhanced Hg(II) uptake over the sulfate concentration ([SO(4)(2-)]) range 10(-5)
      to 0.9 M, increasing Hg surface coverages on goethite, gamma-alumina, and
      bayerite from 0.39 to 0.45 micromol/m(2), 0.11 to 0.38 micromol/m(2), and 0.36 to
      3.33 micromol/m(2), respectively. This effect is likely due to the direct
      sorption or accumulation of sulfate ions at the substrate interface, effectively
      reducing the positive surface charge that electrostatically inhibits Hg(II)
      sorption. Spectroscopic evidence for ternary surface complexation was observed in
      isolated cases, specifically in the Hg-goethite-sulfate system at high [SO(4)(2
      )] and in the Hg-goethite-chloride system.

PMID- 14693131
TI  - Adsorption behavior of selected monosaccharides onto an alumina interface.
AB  - The adsorption of glucose and fructose from their aqueous solutions onto an
      alumina interface has been carried out spectrophotometrically at room
      temperature. The adsorption isotherms are characterized as typical L-type and an
      adsorption mechanism on the basis of dipolar interactions has been suggested. In
      addition to this, a partial role of metal-saccharide interactions as found in
      organometallic complexes (OMCs) for the observed adsorption cannot be ruled out.
      Various kinetic and thermodynamic parameters of the adsorption process have been
      evaluated. The effects of variation in experimental conditions of the system have
      also been investigated. The adsorption exhibited a typical response to the pH
      effect and maximum adsorption was found near the isoelectric point of alumina (pH
      9.0). The anionic addition to the suspension affects the adsorbed amount and Cl(
      ), SO(4)(2-), and PO(4)(3-) affect the adsorption quantitatively. The addition of
      similar concentration of cations was found to reduce the adsorbed amount. The
      presence of cationic and anionic detergents was found to influence both the
      adsorbed amount and the adsorption rate. The temperature was found to have an
      inverse effect on adsorption. Adsorptive kinetic parameters have revealed that
      fructose tends to be a better adsorbate than glucose. This is found to be
      consistent with the chelation behaviour of monosaccharides as found in the OMC of
      monosaccharides. The thermodynamics of the adsorption model indicates its
      spontaneous and exothermic nature. The negative values of entropy are an
      indication of the probability of a favorable nature of adsorption.

PMID- 14693132
TI  - Mechanical and thermodynamic properties of surfactant aggregates at the solid
      liquid interface.
AB  - Surfactants are widely used to stabilize colloidal systems in a variety of
      industrial applications through the formation of self-assembled aggregates at the
      solid-liquid interface. Previous studies have reported that the control of
      surfactant-mediated slurry stability can be achieved through the manipulation of
      surfactant chain length and concentration. However, a fundamental understanding
      of the mechanical and energetic properties of these aggregates, which may aid in
      the molecular-level design of these systems, is still lacking. In this study,
      experimentally measured force/distance curves between an atomic force microscope
      (AFM) tip and self-assembled surfactant aggregates on mica or silica substrates
      at concentrations higher than the bulk critical micelle concentration (CMC) were
      used to determine their mechanical and thermodynamic properties. The experimental
      curves were fitted to a model which describes the interaction between a hard
      sphere (tip) and a soft substrate (surfactant structures) based on a modified
      Hertz theory for the case of a thin elastic layer on a rigid substrate. The
      calculated mechanical properties were found to be in the same order of magnitude
      as those reported for rubber-like materials (e.g., polydimethylsiloxane (PDMS)).
      By integrating the force/distance curves, the energy required for breaking the
      surface aggregates was also calculated. These values are close to those reported
      for bulk-micelle formation.

PMID- 14693133
TI  - Sorption interaction of phenanthrene with soil and sediment of different particle
      sizes and in various CaCl2 solutions.
AB  - The objective of this investigation is to evaluate the influences of natural
      sorbent particle size and system Ca(2+) concentration on sorption of low-polarity
      organic chemicals. The physicochemical properties of the different particle size
      soil and sediment subsamples and the surface characters of the soil and sediment
      samples in various CaCl(2) concentrations were determined. The sorption behavior
      of phenanthrene (PHN) on the subsamples of different particle size and to the
      samples in various CaCl(2) solutions was examined. Batch experiments demonstrate
      that the sorption capacities increase with decreased particle size for both soil
      and sediment. It is presumably due to the higher total organic carbon (TOC)
      content for the finer particles. But the enhancements in sorption coefficients
      are not met with the equal increases in TOC contents. The effect of Ca(2+) on PHN
      uptake is strong in short contact time but slight in long contact time. With
      increasing Ca(2+) concentration, the sorption capacities for Beizhai soil
      increase first in the low Ca(2+) concentration range, and then decline.
      Nevertheless, the increase of Ca(2+) concentration greatly reduces the uptake of
      phenanthrene on Guanting sediment over the overall measured range. The different
      physicochemical properties, such as dissolved organic carbon (DOC) content,
      mineral and element composition, and surface characters, between soil and
      sediment may result in this discrepancy.

PMID- 14693134
TI  - Cu(II) retention on a humic substance.
AB  - Humic substances (HS) are macromolecular products derived from a physical,
      chemical, and microbiological process called "humification." These substances
      play an important role in the mobility and bioavailability of nutrients and
      contaminants in the environment. Adsorption isotherms provide a macroscopic view
      of the retention phenomena. However, complementary techniques are needed in order
      to study the retention mechanism. The application of the classical models and
      some modern ones, based on humic substances chemistry, do not accurately describe
      these adsorption data. The aim of this paper is to model isotherms and combine
      adsorption data with spectroscopy and microscopy techniques to study the Cu(II)
      retention on a HS. The adsorption isotherms shape varies significantly with the
      solution pH from L-type (pH 2-6) to S-type (pH 8). FTIR shows that, when pH is 2
      the retention of Cu(II), as [Cu(H(2)O)(6)](2+), is the preferred retention
      mechanism. The quantity of Cu(II) retained as [Cu(OH)(H(2)O)(6)](+) rises, as pH
      increases. At pH 4, Cu(II) begins to precipitate, which is the preferred
      mechanism at pH 8.02. The presence of HS has a great influence on the
      precipitation process of Cu(II), giving rise to amorphous precipitates. As it is
      shown by SEM-XRF, Cu(II) distributes heterogeneously on HS surface and
      accumulates on the humic phases. The presence of different anions (chloride and
      nitrate) slightly modifies the HS behavior as cation exchanger. When Cl(-) ions
      are present, part of the Cu(II) form [CuCl(4)](2-), which is stable in solution
      due to its negative charge; when the anion present is NO(3)(-) the formed
      complex, [CuNO(3)](+), is retained on the HS.

PMID- 14693135
TI  - Surface complexation modeling of zinc sorption onto ferrihydrite.
AB  - A previous study involving lead(II) [Pb(II)] sorption onto ferrihydrite over a
      wide range of conditions highlighted the advantages of combining molecular- and
      macroscopic-scale investigations with surface complexation modeling to predict
      Pb(II) speciation and partitioning in aqueous systems. In this work, an extensive
      collection of new macroscopic and spectroscopic data was used to assess the
      ability of the modified triple-layer model (TLM) to predict single-solute
      zinc(II) [Zn(II)] sorption onto 2-line ferrihydrite in NaNO(3) solutions as a
      function of pH, ionic strength, and concentration. Regression of constant-pH
      isotherm data, together with potentiometric titration and pH edge data, was a
      much more rigorous test of the modified TLM than fitting pH edge data alone. When
      coupled with valuable input from spectroscopic analyses, good fits of the
      isotherm data were obtained with a one-species, one-Zn-sorption-site model using
      the bidentate-mononuclear surface complex, (triple bond FeO)(2)Zn; however,
      surprisingly, both the density of Zn(II) sorption sites and the value of the best
      fit equilibrium "constant" for the bidentate-mononuclear complex had to be
      adjusted with pH to adequately fit the isotherm data. Although spectroscopy
      provided some evidence for multinuclear surface complex formation at surface
      loadings approaching site saturation at pH >/=6.5, the assumption of a bidentate
      mononuclear surface complex provided acceptable fits of the sorption data over
      the entire range of conditions studied. Regressing edge data in the absence of
      isotherm and spectroscopic data resulted in a fair number of surface-species/site
      type combinations that provided acceptable fits of the edge data, but
      unacceptable fits of the isotherm data. A linear relationship between
      logK((triple bond FeO)2Zn) and pH was found, given by logK((triple bond
      FeO)2Znat1g/l)=2.058 (pH)-6.131. In addition, a surface activity coefficient term
      was introduced to the model to reduce the ionic strength dependence of sorption.
      The results of this research and previous work with Pb(II) indicate that the
      existing thermodynamic framework for the modified TLM is able to reproduce the
      metal sorption data only over a limited range of conditions. For this reason,
      much work still needs to be done in fine-tuning the thermodynamic framework and
      databases for the TLM.

PMID- 14693136
TI  - Treatment of zinc-contaminated water using a multistage ferrihydrite sorption
      system.
AB  - Previous studies demonstrated the environmental and economic benefits of treating
      lead(II)-contaminated water streams with ferrihydrite in multiple equilibrium
      sorption stages. In this work, multistage ferrihydrite sorption systems were
      evaluated for their effectiveness in reducing single-solute zinc(II) (Zn(II))
      concentrations in contaminated water streams to very low levels. As for lead(II)
      (Pb(II)), experimental data and modeling results indicate that a multistage
      sorption system can significantly reduce Zn(II) effluent concentrations for the
      same total amount of sorbent or, alternatively, dramatically lower total sorbent
      consumption for the same effluent Zn(II) concentration. Compared to Pb(II),
      however, Zn(II) removal requires on the order of 10 times more sorbent to achieve
      the same target effluent concentration for the same pH and number of stages.
      Model predictions were made using a steady-state, multistage, equilibrium
      adsorber model that was previously developed for and integrated into OLI Systems'
      Environmental Simulation Program (ESP). The modified triple-layer model was used
      to simulate Zn(II) surface-liquid equilibria within the adsorber model.
      Engineering screening evaluations again indicate that a 2- to 3-stage sorption
      process can provide significant economic savings when compared to a 1-stage
      process operating with the same target effluent Zn(II) concentration. Additional
      equilibrium stages beyond 2 or 3 provide diminishing economic returns. The major
      economic driver for multiple contacting stages is reduced capital investment and
      operating costs for sludge handling, dewatering, and disposal.

PMID- 14693137
TI  - Mechanistic and thermodynamic interpretations of zinc sorption onto ferrihydrite.
AB  - Elucidating the reaction mechanisms and estimating the associated transport and
      thermodynamic parameters are important for an accurate description of the fate of
      toxic metal pollutants, such as Zn(II), in soils and aquatic ecosystems rich in
      iron oxides. Consequently, sorption of Zn(II) ions onto ferrihydrite was
      investigated with macroscopic and spectroscopic studies as a function of pH (4.0
      8.0), ionic strength (10(-3)-10(-1) M NaNO(3)), aqueous Zn(II) concentration (10(
      8)-10(-2) M), and temperature (4-25 degrees C). Present findings suggest that,
      for a given set of pH and temperature conditions, Zn sorption onto ferrihydrite
      can best be described by one average reaction mechanism below the saturation
      limits. Thermodynamic analyses reveal that the Zn(II) ions sorb onto the
      ferrihydrite surfaces via strong endothermic chemical reactions. Consistently, X
      ray absorption spectroscopic (XAS) analyses confirm that, at pH < 6.5, for all Zn
      loadings, Zn(II) ions form corner-sharing, mononuclear, bidentate inner-sphere
      complexes with ferrihydrite, where R(Zn-O) approximately 1.97 A and R(Zn-Fe)
      approximately 3.48 A. For pH >/=6.5, similar sorption complexes were observed at
      lower sorption densities. Then again, for pH >/=6.5 and at higher sorption
      densities, Zn(II) ions may begin to form zinc-hydroxide-like polynuclear sorption
      complexes on the surfaces of the ferrihydrite, where R(Zn-Zn) approximately 3.53
      A. Surprisingly, small changes in temperature had a significant impact on the
      affinity of zinc for the ferrihydrite surface; equilibrium sorption capacity
      decreased by 3-4 orders of magnitude as temperature fell from 25 to 4 degrees C
      for all pH. Zinc sorption onto ferrihydrite, therefore, is governed by pH as well
      as by temperature and sorbate/sorbent ratio.

PMID- 14693138
TI  - Modeling the adsorption of Cd(II) onto kaolinite and Muloorina illite in the
      presence of citric acid.
AB  - The adsorption of cadmium onto kaolinite and Muloorina illite in the presence of
      citric acid has been measured as a function of pH and cadmium concentration at 25
      degrees C. When citric acid is present in the systems cadmium adsorption is
      slightly enhanced below pH 5, but significantly suppressed between pH 5 and 8,
      for both substrates. At higher citric acid concentrations very little cadmium
      adsorbs onto kaolinite from pH 5 to 8. Above pH 8 adsorption of Cd(II) onto
      illite is enhanced in the presence of citric acid, especially at lower
      concentrations, but this does not occur for kaolinite. Adsorption and
      potentiometric titration data were fitted by simple extended constant-capacitance
      surface complexation models for the two substrates. Enhancement of adsorption at
      lower pH values was ascribed to the ternary reaction [X(-)--K(+)](0)+Cd(2+)+L(3
      )+2H(+) right arrow over left arrow (0)+K(+) involving outer-sphere complexation
      with permanently charged X(-) sites on the "silica" faces of both clay minerals.
      The models suggested that suppression of adsorption in the intermediate pH range
      was due to the formation of a strong CdL(-) solution complex which adsorbed
      neither on the permanently charged sites nor on the surface hydroxyl groups at
      the edges of the clay crystals. At higher pH values the dominant solution
      complex, CdLOH(2-), apparently adsorbed as an outer-sphere complex at surface
      hydroxyl groups on illite, SOH+2Cd(2+)+L(3-) right arrow over left arrow [SOCd(+)
      -CdOHL(2-)](-)+2H(+), but not on kaolinite. This difference in behavior results
      from the presence of =FeOH groups on the illite surface which can form surface
      complexes with CdLOH(2-), while the =AlOH groups on the kaolinite surface cannot.

PMID- 14693139
TI  - Microstructured polyacrylamide hydrogels made with hydrophobic nanoparticles.
AB  - Poly(methyl methacrylate) nanosize particles, made by microemulsion
      polymerization, were dispersed in an acrylamide aqueous solution, which was
      polymerized in the presence of a cross-linking agent to yield microstructured
      hydrogels. The kinetics of swelling and the mechanical properties of these
      hydrogels were investigated as a function of concentration of particles. The
      microstructured hydrogels exhibit higher equilibrium swelling and larger Young
      modulus than conventional (that is, without particles) polyacrylamide hydrogel.
      The morphology of the microstructured hydrogels was examined by transmission
      electron microscopy.

PMID- 14693140
TI  - Crystal modification of calcium sulfate dihydrate in the presence of some surface
      active agents.
AB  - The effect of surface-active agents (surfactants), as additives, on the
      crystallization of gypsum was studied under conditions of the simulated dihydrate
      process of phosphoric acid production. Calcium hydrogen phosphate and sulfuric
      acid were mixed with dilute phosphoric acid at 80 degrees C, and the turbidity of
      the reaction mixture was measured at different time periods to determine the
      induction time of gypsum crystal formation. Two types of surfactants, namely,
      cetyltrimethylammonium bromide (CTAB) as a cationic surfactant and sodium dodecyl
      sulfate (SDS) as an anionic surfactant were added to investigate their effects on
      the crystallization of gypsum. Addition of CTAB decreased the induction time and
      increased the growth efficiency, while addition of SDS increased the induction
      time and decreased the growth efficiency compared with the baseline (without
      additives). The surface energy increased with CTAB and decreased with SDS
      compared with the baseline. The percentage of fine crystals decreased in the
      presence of CTAB and increased in the presence of SDS compared with the baseline.
      Gypsum morphology changed from needle-like in the absence of additives to tabular
      in the presence of CTAB.

PMID- 14693141
TI  - Dispersion of organic pigments using supercritical carbon dioxide.
AB  - This research describes dispersion of organic pigments using supercritical
      fluids. With low surface tension and high diffusivity of fluids in supercritical
      states, aggregated particles may be effectively wetted and swelled to form the
      primary constituent of the dispersing solution by volume. In this paper, the
      conditions of temperature and pressure are used to control the density of
      supercritical carbon dioxide subject to PGMEA as cosolvent for dispersing organic
      powder in a solution. As shown from measurement with a laser scattering particle
      analyzer, the average diameter of phthalocyanine green 36 with the haloid
      structure can be significantly reduced to 93.5 nm; for aminoanthraquinone red
      containing and amino group (-NH(2)) and phthalocyanine blue 15:6 with symmetry
      benzene and inner hydrogen bond, the mean particle sizes are 178.5 and 188.7 nm,
      respectively, using supercritical CO(2). Additionally, the transmittance of UV
      light is used to confirm the dispersing performance in this study.

PMID- 14693142
TI  - Removing the effects of additive noise from TIRM measurements.
AB  - Total internal reflection microscopy (TIRM) is an optical technique for
      monitoring Brownian fluctuations in separation between a single microscopic
      sphere and a flat plate in aqueous medium. The sphere is levitated above the
      plate by colloidal forces such as double-layer and steric repulsion. Changes in
      elevation as small as 1 nm can be detected by measuring the light scattered by a
      single sphere when illuminated by an evanescent wave. From the Boltzmann
      distribution of elevations sampled by the sphere over a long time, the potential
      energy (PE) profile can be determined with a resolution of about 0.1 kT. By
      corrupting clean data (having a mean scattering intensity I(s) and standard
      deviation sigma(s)) obtained by Brownian dynamics simulations with various levels
      of white, additive, background noise (having a mean background intensity I(b) and
      standard deviation sigma(b)), we simulate a noisy signal which is then used to
      test various schemes for removal of the noise. Merely subtracting I(b) from the
      measured total intensities before analysis removes the distortion in the PE
      profile when sigma(b)/sigma(s) is less than 0.15. To remove the distortion under
      more severe conditions, we used a Butterworth low-pass filter with the cutoff
      frequency chosen by comparing the power spectral density of the signal with that
      of the noise. This technique was found to be effective in removing distortion
      from the PE profile for cases when sigma(b)/sigma(s) is as large as 2.5.

PMID- 14693143
TI  - XPS study of molybdenum sulfide catalyst exposed to CO and H2.
AB  - Amorphous MoS(3) (air-dried precipitate), crystalline MoS(2) (made in the
      laboratory under nitrogenous atmosphere), and commercial molybdenum disulfide
      catalysts have been investigated by X-ray photoelectron spectroscopy (XPS). The
      chemical species present on the surface and the S/Mo atomic ratios of laboratory
      catalysts were compared to those present on a commercial molybdenum disulfide
      catalyst before and after treatment with CO and H(2). Pretreatment of MoS(2) with
      CO followed by H(2) showed that CO was adsorbed on the surface with no change in
      the chemical oxidation state of Mo and S. However, the results indicated that CO
      was not adsorbed when the sequence of gas exposures was reversed.

PMID- 14693144
TI  - Theoretical study of the surface energy and electronic structure of pyrite FeS2
      (100) using a total-energy pseudopotential method, CASTEP.
AB  - The geometric and electronic structures of FeS(2) (100) surface have been studied
      by a quantum-mechanical calculation using a total-energy pseudopotential code,
      CASTEP. The (100) surface is very stable and does not give any significant
      geometric relaxation. The electronic structure of FeS(2) (100) surface is
      characterized by the appearance of new native surface states in the bulk band
      gap, which correspond to antibonding mixed Fea-Ssp(3) states. These surface
      states play an important role as mediators of electron transfer on both anodic
      and cathodic sites in the incipient oxidation of pyrite. Moreover, the (100)
      surface has small band gaps and shows some metallic character. It is predicted
      that the rate of cathodic reductive reaction of O(2) in the incipient oxidation
      of pyrite is much faster than previously considered. The transport of electrons
      from the anodic sites to the cathodic sites on the (100) surface is faster and
      hole injection of anodic sites is not the rate-determining step. So we can deduce
      that the rate-determining step of incipient oxidation for pyrite consists of both
      electron transfer of pyrite/aqueous O(2) interface and the splitting of H(2)O.

PMID- 14693145
TI  - Time-dependent complexation of glucose-reduced gold nanoparticles with
      octadecylamine Langmuir monolayers.
AB  - We report on the reduction of aqueous chloroaurate ions by glucose to form gold
      nanoparticles of uniform size. We further demonstrate the complexation of these
      particles with octadecylamine (ODA) monolayers at the air-water interface.
      Pressure-area (pi-A) isotherms as a function of time of complexation revealed a
      significant expansion of the monolayer. Surface pressure variation with time for
      constant areas after spreading of the monolayer was carried out to observe the
      kinetics of complexation of the colloidal particles at the interface. The
      kinetics of complexation of the particles at the interface was also monitored by
      Brewster angle microscopy (BAM) measurements. Langmuir-Blodgett films of the
      particles complexed with ODA were formed at a subphase pH of 9 onto different
      substrates. Quartz crystal microgravimetry (QCM) was used to quantify the amount
      of particles deposited per immersion cycle of the quartz crystal. The LB films
      were further characterized by UV-vis and transmission electron microscopy (TEM)
      measurements. TEM measurements indicate a close packed and equidistant
      arrangement of colloidal particles in the LB film, probably due to hydrogen
      bonding interactions.

PMID- 14693146
TI  - Effect of boron on the surface tension of molten silicon and its temperature
      coefficient.
AB  - The influence of boron concentration (C(B)/mass%) on the surface tension of
      molten silicon has been investigated with the sessile drop method under oxygen
      partial pressure P(O(2))=1.62x10(-25)-2.63x10(-22) MPa, and the results can be
      summarized as follows. The surface tension increases with C(B) in the range below
      2.09 mass%, and the maximum increase rate of the surface tension is about 30 mN
      m(-1)(mass% C(B))(-1). The temperature coefficient of the surface tension, (
      partial differential sigma/ partial differential T)C(B), was found to increase
      with the boron concentration in molten silicon. At the interface between molten
      silicon and the BN substrate, a discontinuous Si(3)N(4) layer was reckoned to
      form and the layer might prevent BN from dissolving into the molten silicon.
      Since dissolved boron from the BN substrate into the molten silicon is below
      0.054 mass% and the associated increase in surface tension is below 1.5 mN m(-1),
      the contamination from the BN substrate on the surface tension can be ignored.
      The relation between the surface tension and C(B) indicates negative adsorption
      of boron and can be well described by combining the Gibbs adsorption isotherm
      with the Langmuir isotherm.

PMID- 14693147
TI  - Nonlinear penetration of liquid drops into radial capillaries.
AB  - The nonlinear dynamics of the impact and penetration of a liquid droplet in a
      radial capillary is studied numerically. The radial capillary is formed by two
      parallel plates at a distance of delta(g). The top plate has an orifice at its
      center. A droplet impacting on the orifice-plate partly spreads over the top
      plate, and the rest penetrates into the capillary gap between the two plates. The
      rate of spread of the fluid on the orifice plate, xi(out), is governed by the
      contact angle, beta, between the liquid and the orifice plate and the droplet
      initial momentum, whereas the rate of fluid spread inside the capillary gap,
      xi(in), is decided by the contact angles with both plates and the plate gap,
      delta(g).

PMID- 14693148
TI  - A study of interfacial dilational properties of two different structure
      demulsifiers at oil-water interfaces.
AB  - The interfacial dilational viscoelastic properties of two demulsifiers with
      straight chain (SP-169) and branched chain (AE-121) at the oil-water interfaces
      were investigated by means of the longitudinal waves method and the interfacial
      tension relaxation method, respectively. The results obtained by the longitudinal
      waves method showed that the dilational viscous component for AE-121 and SP-169
      also passed through a maximum value with increasing concentration. It was found
      that the maximum value appeared at different demulsifier concentrations during
      our experiment frequency; and the higher is the dilational frequency, the lower
      is the concentration. The influences of AE-121 and SP-169 on the dilational
      viscoelastic properties of the oil-water interface containing surface-active
      fraction from Iranian crude oil have been measured. The results clearly stated
      that both demulsifiers could obviously decrease the dilational elasticity of oil
      water interface containing surface-active fraction. At low concentration, because
      of stronger adsorption ability, SP-169 has stronger ability to decreasing the
      dilational modulus than AE-121. We also found that the dilational modulus of the
      interface contained surface-active fraction passed through a minimum value with
      increasing demulsifier concentration for both demulsifiers. This result indicated
      the dosage of demulsifier had an optimum value. The results obtained by means of
      interfacial tension relaxation method showed that the slow relaxation processes
      involve mainly rearrangement in the conformation of the molecules appeared with
      increasing demulsifier concentration.

PMID- 14693149
TI  - The possibility of different time scales in the dynamics of pore imbibition.
AB  - To model the imbibition of liquids into porous solids, use is often made of the
      Lucas-Washburn equation, which relates the distance of penetration of a liquid at
      a given time to the pore radius, the viscosity and surface tension of the liquid,
      and the effective contact angle between the liquid and the solid. In this paper,
      we extend previous large-scale molecular dynamics simulations to show how this
      tool can be used to study the details of liquid imbibition, including the impact
      of the contact angle on the dynamics of penetration and the evolution of the
      internal flow field. In particular, we show that the asymptotic behavior of the
      contact angle versus time for a completely wetting liquid is given by
      approximately t(-1/4).

PMID- 14693150
TI  - Spontaneous rise of surfactant solutions into vertical hydrophobic capillaries.
AB  - It has been found earlier (N.V. Churaev, G.A. Martynov, V.M. Starov, Z.M. Zorin,
      Colloid Polym. Sci. 259 (1981) 747) that aqueous surfactant solutions
      spontaneously rise in vertical hydrophobized quartz capillaries. A theory of this
      phenomenon is presented, which connects the experimental observations with the
      adsorption of surfactant molecules in front of the moving meniscus on the bare
      hydrophobic interface.

PMID- 14693151
TI  - Polymer-induced structural changes in lecithin/sodium dodecyl sulfate-based
      multilamellar vesicles.
AB  - Aqueous concentrated lecithin mixtures (asolectin from soybean) show typical
      lamellar liquid crystalline behavior and the individual lamellae tend to form
      spherical supramolecular structures, i.e., multilamellar vesicles. When part of
      the lecithin is replaced by the anionic surfactant sodium dodecyl sulfate (SDS),
      the compact multilamellar vesicles disappear and the viscosity decreases. By
      adding poly(diallyldimethylammonium chloride) (PDADMAC) to the lecithin/SDS
      system, the formation of multilamellar vesicles can be induced again and the
      viscosity increases. However, one characteristic feature of these polymer
      modified systems is a temperature-dependent phase transition from a compact
      multilamellar vesicle phase to a more swollen liquid crystalline phase. The
      polymer-modified multilamellar compact vesicles are of interest for utilization
      as new thermosensitive drug delivery systems.

PMID- 14693152
TI  - Formation of shaped drops in a fast continuous flow process.
AB  - Drop shaping, i.e., flow-induced deformation and fixation by gel formation, was
      studied under dynamic conditions in a fast continuous process for a water-in-oil
      system. The system consisted of sunflower oil with different surfactant
      concentrations (0.1-2% Admul Wol) and a 1.5% kappa-carrageenan solution with
      different Na(+) and K(+) concentrations. The continuous phase flowed in a 10-mm
      wide straight channel into which the dispersed phase was injected via a thin
      needle. A subsequent shaping channel with a width of 1 or 2 mm deformed the
      drops. Gel formation was induced by a temperature gradient between the continuous
      and dispersed phase. Drop sizes in the range 220-roughly 1000 microm were
      produced at the needle tip by varying the ratio between the oil and carrageenan
      flow rate. A diffusion zone before the narrow channel allowed the surfactant to
      adsorb at the interface. In the elongation flow at the entrance of the shaping
      geometry, drops underwent initial elongation. In the narrow channel, the drops
      developed a parabolic shape within a residence time of 0.03-0.15 s. Choosing the
      correct parameter combinations made it possible to fix the deformation by gel
      formation within this time period. Shaped drops were shown to be functional. At a
      concentration of 25% in an emulsion, they increased the viscosity by about 15-20%
      compared to spherical drops even though 45% of the shaped drops had an aspect
      ratio of less than 1.2.

PMID- 14693153
TI  - Buoyancy-driven coalescence of spherical drops covered with incompressible
      surfactant at arbitrary Peclet number.
AB  - Collision efficiencies are determined for two surfactant-covered spherical drops
      in the limits of nearly uniform surface coverage and bulk insolubility for
      Brownian and/or gravitational motion as a function of drop-size ratio, drop-to
      medium viscosity ratio, and retardation parameter. For two equal-sized drops in
      Brownian motion in the limit of small viscosity ratio, the calculated collision
      efficiencies agree well with earlier results for bubbles. While the two-sphere
      relative mobility functions for motion parallel to the drops' line of centers
      tend to the same values in the limits of infinite viscosity ratio and infinite
      retardation parameter, the asymmetric mobility functions do not, because the
      coefficients for the rotational term in Lamb's singular solution are independent
      of the presence of surfactant. The complex dependence of the transverse mobility
      functions on the viscosity ratio and retardation parameter makes it possible for
      the gravitational collision efficiency to increase slightly with viscosity ratio
      at fixed size ratio and retardation parameter of O(10(3)) or larger. Typical
      hydrosols are also studied in gravitational motion at arbitrary Peclet number,
      showing the combined influence of Brownian and gravitational motion.

PMID- 14693154
TI  - Preparation characteristics of water-in-oil-in-water multiple emulsions using
      microchannel emulsification.
AB  - Microchannel (MC) emulsification is a novel technique for preparing monodispersed
      emulsions. This study demonstrates preparing water-in-oil-in-water (W/O/W)
      emulsions using MC emulsification. The W/O/W emulsions were prepared by a two
      step emulsification process employing MC emulsification as the second step. We
      investigated the behavior of internal water droplets penetrating the MCs. Using
      decane, ethyl oleate, and medium-chain triglyceride (MCT) as oil phases, we
      observed successful MC emulsification and prepared monodispersed oil droplets
      that contained small water droplets. MC emulsification was possible using
      triolein as the oil phase, but polydispersed oil droplets were formed from some
      of the channels. No leakage of the internal water phase was observed during the
      MC emulsification process. The internal water droplets penetrated the MC without
      disruption, even though the internal water droplets were larger than the
      resulting W/O/W emulsion droplets. The W/O/W emulsion entrapment yield was
      measured fluorometrically and found to be 91%. The mild action of droplet
      formation based on spontaneous transformation led to a high entrapment yield
      during MC emulsification.

PMID- 14693155
TI  - Thermodynamic method for prediction of surfactant-modified oil droplet contact
      angle.
AB  - A model applying surfactant self-assembly theory and classical thermodynamics has
      been developed to aid in the prediction of solid surface cleaning by aqueous
      surfactant solutions. Information gained from a combination of surfactant self
      assembly behavior and cleaning system parameters, such as oil species, surfactant
      type, temperature, alkalinity, and solid surface type has been shown to provide
      insight into surface cleaning. The model combines minimization of free energy,
      pertinent component distribution mechanisms, and surfactant self-assembly
      processes to provide a methodology for the predicting of oil droplet contact
      angles. Such predictive capabilities will allow for the development of beneficial
      environmental and economic changes to industrial and commercial surface cleaning
      and degreasing processes. Results from the model will be compared to experimental
      data to verify the capability of the theory to account for the effect of
      solutions parameters on oil droplet behavior. The model, while approximate in
      nature, has shown a remarkable quantitative predictive ability.

PMID- 14693156
TI  - Electroosmotic flow in channels with step changes in zeta potential and cross
      section.
AB  - We consider the effects that step changes in zeta potential and cross section
      have on electroosmosis in long-and-narrow channels with arbitrary cross-sectional
      shapes. The Stokes equation of flow is solved analytically utilizing the thin
      Debye layer approximation to provide effective slip velocities on the channel
      walls. The effects of channel dimensions, surface potentials, applied pressure
      drop, and applied voltage are discussed. One anecdotal case, a two-region
      rectangular channel, is presented to illustrate the solution. The flow in each
      region is a combination of a uniform electroosmotic flow and a nonuniform
      pressure-driven flow. The electroosmotic pumping causes the pressure gradient in
      each region to adjust so that the flow rate is the same in each region and the
      overall applied pressure drop is met, resulting in convex velocity profiles in
      some regions and concave velocity profiles in other regions. By appropriate
      choice of the applied pressure drop, flat velocity profiles may be achieved in
      one or more regions.

PMID- 14693157
TI  - Self-similar etching.
AB  - When a fiber is brought into contact with a soft etching liquid, a conical tip is
      generally shaped. We show here that the use of corrosive liquids which release
      gases during the etching reaction may lead to original self-similar shapes,
      because of successive pinning and detachment of the meniscus. The conditions for
      the formation of this shape and its evolution are described. In particular, we
      stress the effect of convection due to released bubbles.

PMID- 14693158
TI  - Dense colloid transport in a bifurcating fracture.
AB  - In this work, the transport of dense colloids through a water-saturated,
      bifurcating fracture is investigated using a constant spatial step particle
      tracking technique. The size of the constituents of a colloid plume is an
      important factor affecting the partitioning of dense colloids at the bifurcation.
      While neutrally buoyant colloids partition between daughter fractures in
      proportion to flow rates, dense colloids will preferentially exit fractures that
      are gravitationally downgradient, notwithstanding that the majority of the
      interstitial fluid may flow through the upper fracture. Comparison of the
      partitioning ratio between daughter fractures with the ratios of characteristic
      settling, diffusion, and advection time reveal that these parameters control how
      colloids behave at fracture bifurcations.

PMID- 14693159
TI  - Opposing roles for TGF-beta1 and TGF-beta3 isoforms in experimental autoimmune
      encephalomyelitis.
AB  - Hormones can exert significant protective effects on autoimmune diseases by
      activating immunoregulatory mechanisms. One of the possible mechanisms of
      hormonal protection might be through the anti-inflammatory effects of the TGF
      beta molecule. The present study investigated the changes in expression of two
      TGF-beta isoforms, TGF-beta1 and TGF-beta3, in C57BL/6 and TCR transgenic (T/R+)
      B10.PL mice that manifested or were protected against clinical signs of
      experimental autoimmune encephalomyelitis (EAE) with 17beta-estradiol (E2)
      treatment. We here demonstrate an inverse relationship between expression of TGF
      beta1 that is enhanced in mice with EAE, and TGF-beta3 that is enhanced in E2
      protected mice. The differential expression of TGF-beta isoforms was observed in
      spinal cord tissue but not spleen. Additionally TGF-beta1 expression was evident
      both in whole spinal cord tissue and mononuclear cells isolated from inflamed
      tissue, in contrast to TGF-beta3 that was only detected in spinal cord tissue but
      not in mononuclear cells. Further studies revealed that CD3 and especially MAC-1
      positive cells were the main source of TGF-beta1 in the mononuclear CNS
      population. Of crucial importance, the TGF-beta3 isoform displayed anti
      proliferative properties towards encephalitogenic cells in vitro. We propose that
      the TGF-beta1 and TGF-beta3 isoforms play opposing roles in the expression of
      EAE.

PMID- 14693160
TI  - AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl.
AB  - Thrombopoietin (TPO) plays a pivotal role in megakaryopoiesis. TPO initiates its
      biological effects by binding to its receptor Mpl. A recombinant protein
      consisting of a carrier Fc domain linked to multiple Mpl-binding domains was
      constructed, and is called AMG531. To define the biological activity of AMG531,
      we examined the ability of AMG531 to support CFU-Meg growth and to promote
      megakaryocyte maturation in vitro. AMG531 stimulates CFU-Meg growth in a dose
      dependent manner, and acts in concert with erythropoietin, stem cell factor,
      interleukin-3, and interleukin-6 to enhance CFU-Meg growth, similar to parallel
      experiments with TPO. AMG531-stimulated serum-free liquid cultures support the
      development of mature polyploid megakaryocytes with a predominant DNA content of
      32 N and 64 N, identical to that of parallel TPO-stimulated cultures. Competitive
      binding experiments show that AMG531 effectively competes with 125I-TPO for
      binding to BaF3-Mpl cells or normal platelets. Treatment of BaF3-Mpl cells with
      AMG531 or with TPO resulted in rapid tyrosine phosphorylation of Mpl, JAK2, and
      STAT5. These results indicate that AMG531 is a potent stimulant of
      megakarypoiesis in vitro, and provide support for its further characterization in
      vivo.

PMID- 14693161
TI  - Interleukin-4 inhibits platelet-derived growth factor-induced preadipocyte
      proliferation.
AB  - Interleukin-4 (IL-4) activates STAT6 in 3T3-L1 preadipocytes but its functional
      role is not known. In this report, we first assessed interleukin-4 receptor alpha
      (IL-4Ralpha) expression during adipogenesis. IL-4Ralpha was highly expressed in
      proliferating 3T3-L1 preadipocytes. Receptor expression was down-regulated in
      post-confluent growth arrested preadipocytes. Induction of differentiation led to
      a transient 36-h increase in expression, but then levels decreased to
      undetectable amounts 3-8 days after induction of differentiation. Depending on
      the cell type, IL-4 either increases or decreases cell proliferation. In growth
      arrested preconfluent 3T3-L1 preadipocytes, IL-4 alone had no effect on
      preadipocyte proliferation. In contrast, IL-4 inhibited platelet-derived growth
      factor (PDGF-BB) induced preadipocyte proliferation. PDGF-BB, but not IL-4,
      induced STAT3 tyrosine and AKT serine phosphorylation. Both PDGF-BB and IL-4
      induced STAT6 tyrosine phosphorylation, but the bands showed distinct
      electrophoretic migration patterns. IL-4 alone and IL-4 added to the
      differentiation cocktail had no effect on adipocyte formation or PPARgamma
      expression. Collectively, these studies demonstrate that IL-4 inhibits PDGF-BB
      induced preadipocyte proliferation, possibly through STAT6 activation. The
      pattern of IL-4 receptor expression suggests that the effects of IL-4 are
      targeted primarily towards preadipocytes.

PMID- 14693162
TI  - The effects of surgery, with or without rhGM-CSF, on the angiogenic profile of
      patients treated for colorectal carcinoma.
AB  - Wound healing is a process with immunological and angiogenic aspects. rhGM-CSF is
      known to stimulate the immune system and angiogenesis via multiple pathways. In
      this study we investigated the combined effects of surgery, with or without rhGM
      CSF, on angiogenic parameters in patients with a colorectal carcinoma. In this
      phase II randomized, placebo-controlled trial, 16 patients were assigned to
      perioperative rhGM-CSF (2.8 microg/kg body weight) treatment or saline. Patients
      received subcutaneous injections from three days before surgery until four days
      after. IL-6, VEGF, endostatin and angiostatin levels were measured
      perioperatively. rhGM-CSF enhanced the production of IL-6 and VEGF, but had no
      effect on the antiangiogenic agents endostatin and angiostatin. Surgery induced a
      transient decrease of endostatin. Two types of angiostatin (kringle 1-3 and
      kringle 1-4) became visible postoperatively. We conclude that this study
      demonstrated the immediate initiation of angiogenesis postoperatively, reflected
      by the increase of VEGF and a transient decrease of endostatin, followed by the
      appearance of two angiostatin bands, which confirms physiological wound healing
      in these cancer patients.

PMID- 14693163
TI  - Ex vivo induction of cytokines by mould components in whole blood of atopic and
      non-atopic volunteers.
AB  - We investigated the time-course release of IL-1beta and IL-8 protein as well as
      the steady state mRNA level of their genes in human whole blood after stimulation
      with LPS, beta-1,3-D-glucan and mould extracts. We compared the response of 10
      non-atopic and 10 atopic individuals. In parallel, cytokine protein release and
      the corresponding steady state mRNA level was determined by the standard ELISA
      and real-time on-line RT-PCR methods, respectively. Glucan induced the highest
      level of IL-1beta mRNA and protein release after 3 h. IL-8 was induced at 3 h
      after glucan, but not after LPS, induction, which indicates different induction
      pathways. At the time-points found to elicit the optimal cytokine response
      significantly higher basal cytokine mRNA levels and significantly lower LPS
      induced cytokine mRNA levels were observed in the non-atopic group. Generally,
      mould components induced cytokine mRNA steady state to lower levels in the
      atopics compared to the non-atopics. In contrast, no differences were found
      between the two groups in their capacity to induce cytokine protein release.
      These findings persisted after correction for the percentage of mononuclear
      cells. The data supported our hypothesis that "exhaustion" of the atopic immune
      system elicits lower basal cytokine mRNA levels and that analysis of cytokine
      gene expression has the potential to differentiate between non-atopic and atopic
      individuals.

PMID- 14693164
TI  - Thrombosis in children with acute lymphoblastic leukemia. Part II. Pathogenesis
      of thrombosis in children with acute lymphoblastic leukemia: effects of the
      disease and therapy.
AB  - At diagnosis, there is evidence of increased thrombin generation in children with
      acute lymphoblastic leukemia (ALL), the etiology of which is unclear. However,
      thromboembolism (TE) in children with ALL is most commonly reported after the
      initiation of antileukemic therapy indicating a possible interaction of the
      disease and therapy. Antileukemic therapy influences the haemostatic system
      either by direct effect of the chemotherapeutic agents or indirectly through the
      effect of supportive care, e.g. central venous line (CVL) or infectious
      complications secondary to immunosuppression. Asparaginase and steroids are shown
      to induce hypercoagulable state by suppression of natural anticoagulants,
      especially AT and plasminogen, and by elevations in F VIII/vWF complex,
      respectively. In addition, steroid therapy causes hypofibrinolytic state by dose
      dependent increase in plasminogen activator inhibitor 1 (PAI-1) levels.
      Combination of these effects coupled with increased thrombin generation may be
      responsible for the increased incidence of TE observed with concomitant
      administration of asparaginase and steroids. Further studies to delineate the
      mechanism of increased thrombin in generation children with ALL and effects of
      various chemotherapeutic agents, in isolation and in combination, on haemostatic
      system are needed.

PMID- 14693165
TI  - Editorial to the study by Panju A. et al. "Venous thromboembolism prophylaxis in
      medical inpatients: a retrospective chart review".

PMID- 14693166
TI  - Venous thromboembolism prophylaxis in medical inpatients: a retrospective chart
      review.
AB  - BACKGROUND: Venous thromboembolic disease (VTE) is a major cause of morbidity and
      mortality in hospitalized patients. Most hospitalized patients with a fatal
      pulmonary embolism are medical patients who do not have a history of recent
      surgery [BMJ 302 (1991) 709; J. R. Soc. Med. 82 (1989) 198]. There is evidence
      suggesting that VTE prophylaxis is indicated in many high risk medical patients
      [Chest 119 (2001) 132S; NEJM 341 (1999) 793]. However, previous studies have
      shown that only about one third of high risk medical patients receive VTE
      prophylaxis [Ann. Intern. Med. 115 (1991) 591; Chest 106 (1994) 13; Chest 107
      (1995) 296]. The objective of this study was to determine the frequency of use of
      VTE prophylaxis in medical inpatients at two teaching hospitals in Hamilton,
      Ontario. METHODS: A retrospective chart review of consecutive patients admitted
      to medical wards at two acute care sites of McMaster University affiliated
      teaching hospitals between October 10, 2001 and December 11, 2001 was performed.
      For each patient, demographic data, risk factors for VTE, method of VTE
      prophylaxis and contraindications to VTE prophylaxis were recorded. RESULTS: 756
      patient charts were reviewed and 310 (41%) were excluded because the primary
      diagnosis required anticoagulation, the patients were being treated with
      anticoagulation (warfarin or heparin) before admission or the patient was
      admitted to the intensive care unit. Of the remaining 446 patients, 146 (33%)
      received some form of VTE prophylaxis. Of the patients receiving prophylaxis, 4%
      had early ambulation, 9% wore anti-embolic stockings (AES), 1% used intermittent
      pneumatic compression, 23% used unfractionated heparin and 3% used low molecular
      weight heparin. Two hundred five (46%) patients had one identifiable VTE risk
      factor and 63 (14%) had two or more risk factors. Patients with more VTE risk
      factors were more likely to receive prophylaxis. INTERPRETATION: One third of
      medical inpatients at two teaching hospitals in Hamilton received some form of
      VTE prophylaxis.

PMID- 14693167
TI  - Thrombogenesis and endothelial damage/dysfunction in peripheral artery disease.
      Relationship to ethnicity and disease severity.
AB  - Peripheral artery disease (PAD) and intermittent claudication are common in men
      aged over 55 years. Once the diagnosis has been made, very few patients suffer
      from a deterioration of the disease. Those that do deteriorate tend to do so due
      to thrombosis of an affected artery. It is apparent that the disruption in the
      vessel wall accounts for some of the cause of the thrombosis but blood
      constituents also play a role. We hypothesized that levels of soluble P-selectin
      (sP-sel, a marker of platelet activation), von Willebrand factor (vWf, an index
      of endothelial damage/dysfunction), tissue factor (TF, a coagulation protein
      involved in the 'extrinsic' coagulation pathway) and fibrinogen would be
      abnormally elevated in relation to disease severity and correlated with each
      other, and related to ethnicity, in a multiethnic population of patients with
      PAD. To test this hypothesis, we studied 234 patients (80% white, 7% Indo-Asian,
      13% Afro-Caribbean) with confirmed PAD [ankle brachial pressure index (ABPI)< or
      =0.8] and 50 healthy controls. All of the indices studied were increased in
      patients over controls (p<0.05). None of the indices of the hypercoagulable state
      were significantly different between the three ethnic groups studied. Patients
      with ischaemic rest pain were shown to have higher levels of plasma fibrinogen
      (p<0.001) although none of the other prothrombotic markers were increased in this
      group. Furthermore, fibrinogen was higher in cases whose ABPI was below the
      median (<0.52) when compared to those less severely affected, with an inverse
      correlation between fibrinogen and ABPI (Spearman, r=-0.178, p=0.009). In
      conclusion, we found a prothrombotic state in patients with PAD with increased
      levels of markers of endothelial damage/dysfunction, platelet activation and
      thrombosis, which may contribute to the pathogenesis of this condition. However,
      disease severity was only related to plasma fibrinogen levels.

PMID- 14693168
TI  - A cross-sectional study evaluating post-thrombotic syndrome in children.
AB  - BACKGROUND: Post-thrombotic syndrome (PTS) in adults, characterized by swelling,
      skin pigmentation, pain, and ulceration of the limb, is secondary to deep vein
      thrombosis (DVT). In contrast to the extensive documentation on PTS in adults,
      little is known about the risk of PTS in children. OBJECTIVE: To determine the
      incidence, clinical characteristics, and predictors of PTS in children. METHODS:
      A cross-sectional study in 153 nonselected children with objectively confirmed
      DVT. All children were assessed for PTS using a standardized score. As per the
      PTS score, severity was classified as: absent, mild, moderate, or severe.
      RESULTS: Post-thrombotic syndrome was present in 96/153 children (63%), in which
      80 (83%) were mild and 16 (17%) were moderate. Swelling was the most frequently
      recorded subjective symptom (43%) while increased limb circumference (71%) and
      presence of collateral circulation (53%) were the most frequently recorded
      objective symptoms. Risk factors for development of PTS were: lack of resolution
      of the DVT by radiographic assessment (OR 3.96, 95% CI 1.68-9.30), number of
      vessels involved in the initial DVT (OR 2.05, 95% CI 1.52-2.77), and length of
      follow-up (OR 1.22, 95% CI 1.08-1.39). CONCLUSIONS: These findings demonstrate
      that PTS is a clinically significant disease in children with previous DVT.

PMID- 14693169
TI  - Thrombosis in patients with paroxysmal noctural hemoglobinuria is associated with
      markedly elevated plasma levels of leukocyte-derived tissue factor.
AB  - Thromboembolism is a frequent complication of paroxysmal nocturnal hemoglobinuria
      (PNH) and contributes significantly to patient morbidity and mortality. A number
      of mechanisms have been proposed to explain the increased incidence of this
      complication of PNH. Increased platelet activation with platelet microparticle
      formation and depression of cell surface-mediated fibrinolysis has been
      demonstrated in patients with PNH. We have studied two patients with hemolytic
      PNH who had recurrent and refractory venous thromboembolic events despite
      therapeutic anticoagulation. Plasma samples from both patients demonstrated
      marked hemostatic activation as determined by elevated plasma thrombin
      antithrombin complexes (TAT) and D-dimers. Plasma samples from both patients were
      also shown to contain markedly elevated levels of circulating tissue factor (TF),
      which was shown to be predominantly derived from monocytes and macrophages. In
      one patient, a successful allogeneic bone marrow transplant resulted in a
      reduction in hemostatic activation associated with a marked decrease in
      circulating tissue factor to near normal levels. We propose that thrombosis in
      PNH results from increased tissue factor expression by complement injured CD55-
      and CD59-deficient monocytes and macrophages.

PMID- 14693170
TI  - Long-term outcome of deep venous thrombosis during pregnancy treated with
      unfractionated heparin or low molecular weight heparin.

PMID- 14693171
TI  - Platelet activity and antibody titers after exposure to streptokinase or
      streptococcal infection.
AB  - INTRODUCTION: Streptokinase use, in acute myocardial infarction, is hindered by
      failure to reperfuse (60%) and early reocclusion (16%). This phenomenon may,
      among other causes, be due to systemic inactivation of streptokinase, as well as
      streptokinase-induced platelet aggregation and clot propagation from antibodies
      to streptokinase produced after streptokinase administration or streptococcal
      infections. The purpose of this study was to determine the incidence of
      streptokinase-induced, antibody-mediated, platelet activation and aggregation
      after administration of SK or development of a streptococcal infection. MATERIALS
      AND METHODS: We included 45 normal volunteers (Control group), as well as 45
      patients who had received streptokinase (Streptokinase group) and 13 who had
      suffered a severe streptococcal infection (Streptococcal infection group) within
      the past 3 years. Extent of streptokinase-induced, antibody-mediated, platelet
      activation and aggregation, as well as anti-streptokinase antibody and
      streptokinase resistance titers (lowest streptokinase concentration to cause clot
      lysis within 10 min) were measured. RESULTS: Whereas streptokinase-induced,
      antibody-mediated, platelet activation was observed in 49% of streptokinase
      patients and in only 17% and 15% of streptococcal infection patients and normal
      volunteers (p<0.05 Streptokinase vs. Control and Streptokinase vs. Streptococcal
      infection), streptokinase-induced platelet aggregation was observed in 23% of
      streptokinase patients and streptococcal infection patients, and in none of the
      control patients (p<0.05). CONCLUSIONS: Streptokinase-induced, antibody-mediated,
      platelet activation and aggregation occur in patients with high titers of anti
      streptokinase antibody and may play a role in failure of streptokinase therapy.
      Streptococcal infection patients behave like streptokinase patients in terms of
      the reactivity of their platelets to subsequent streptokinase dose in vitro.

PMID- 14693172
TI  - Effects of the NHE-1 inhibitor cariporide alone or together with the P2Y12
      antagonist AR-C 69331 MX on CD62p expression and formation of platelet-leukocyte
      aggregates.
AB  - The sodium-hydrogen exchanger isoform 1 (NHE-1) contributes to platelet
      activation at elevated pH. Effects of NHE-1 inhibitors on platelet degranulation
      and formation of proinflammatory and procoagulatory platelet-leukocyte aggregates
      (PLA) and possible interactions with P2Y(12) inhibitors--which also affect
      platelet degranulation--have not been investigated. Whole blood from healthy
      human subjects was incubated with the NHE-1 inhibitor cariporide and the P2Y(12)
      inhibitor AR-C 69331 MX at clinically reasonable concentrations, in the presence
      of normal pH or in a propionate model to activate the NHE-1 (approximately pH
      7.0). The degranulation marker CD62p, the expression of the activated GPIIb/IIIa
      receptor (PAC-1), and formation of platelet-leukocyte (monocyte) aggregates (PLA)
      was assessed by flow cytometry. Cariporide at concentrations up to 20 microg/ml
      had no effects on ADP- (5 microM) or TRAP- (2 microM) induced CD62p expression or
      PLA formation at normal pH. At pH 7.0 and stimulation with ADP, PLA decreased
      from 64+/-24% (control) to 47+/-23% under cariporide at 2 microg/ml (p<0.05), and
      the MFI of PLA (i.e. the platelet mass attached at monocytes) decreased from
      547+/-203 to 360+/-96 units (p<0.05). PAC-1 MFI decreased from 66+/-23 to 34+/-18
      units (p<0.05) after ADP and from 74+/-29 to 42+/-17 units (p<0.05) after TRAP,
      respectively. AR-C 69331 MX (10 nM) had inhibitory effects on all parameters
      irrespectively of the pH, and the combination of both agents at pH 7.0 shows
      additive effects. In conclusion, our investigation points to-perhaps clinically
      relevant-effects of NHE-1 inhibition on the degranulation of platelets and
      formation of platelet-leukocyte aggregates.

PMID- 14693173
TI  - Effective anti-platelet and COX-1 enzyme inhibitors from pungent constituents of
      ginger.
AB  - BACKGROUND: Based on recent studies, pungent constituents of ginger (Zingiber
      officinale) and related substances represent a potential new class of anti
      platelet agents. The ability of 20 pungent constituents of ginger and related
      substances to inhibit arachidonic acid (AA) induced platelet activation in human
      whole blood was studied. METHODS: Anti-platelet activity of the compounds was
      measured in vitro by the Chrono Log whole blood platelet aggregometer. Molecular
      hydrophobicity (log P) was measured by reversed-phase high-performance liquid
      chromatography. COX-1 (ovine) inhibitory effect of [8]-paradol and analogues 1
      and 5 was carried out using a COX-1 inhibitor assay kit. RESULTS: [8]-Gingerol,
      [8]-shogaol, [8]-paradol and gingerol analogues (1 and 5) exhibited anti-platelet
      activities with IC(50) values ranging from 3 to 7 microM, whilst under similar
      conditions the IC(50) value for aspirin was 20+/-11 microM. The COX-1 inhibitory
      activity of [8]-paradol (IC(50)=4+/-1 microM) was more potent than the gingerol
      analogues (1 and 5) (IC(50) approximately 20 microM). CONCLUSION: The above
      findings show that gingerol compounds and their derivatives are more potent anti
      platelet agents than aspirin under the conditions described in this study. [8]
      Paradol, a natural constituent of ginger, was found to be the most potent COX-1
      inhibitor and anti platelet aggregation agent. The mechanism underlying AA
      induced platelet aggregation inhibition may be related to attenuation of COX-1/Tx
      synthase enzymatic activity. Lastly, important features of phenolic compounds for
      inhibition of AA-induced platelet aggregation and COX-1 activity were revealed in
      this study.

PMID- 14693174
TI  - The effects of acute exercise on plasma antioxidant status and platelet response.

PMID- 14693175
TI  - Dextran sulfate included in factor Xa assay reagent overestimates heparin
      activity in patients after heparin reversal by protamine.
AB  - A lack of correlation between activated partial thromboplastin time (aPTT),
      thrombin time (TT) and anti-factor Xa (AXa) activity was observed in patients
      after cardiac surgery with cardiopulmonary bypass (CBP). Indeed, AXa activity
      measured by the chromogenic assay, Coamatic Heparin, was higher than expected
      with regard to results obtained in coagulation assays. To account for this
      discrepancy, another AXa chromogenic assay was tested. First, AXa activity was
      measured with two chromogenic assays (Coamatic Heparin and Rotachrom Heparin) in
      plasma samples of 25 patients undergoing cardiac surgery at two time points after
      heparin reversal by protamine. AXa activity was significantly higher when
      measured with Coamatic Heparin than with Rotachrom Heparin in samples collected
      just after protamine infusion (p<0.01). Next, since Coamatic( Heparin contains
      dextran sulfate (DXS) to reduce the influence of heparin antagonists such as
      platelet factor 4 (PF4), whereas Rotachrom Heparin does not, we hypothesized that
      the dextran sulfate contained in the reagent might explain this discrepancy. We
      therefore performed in vitro studies consisting in neutralizing unfractionated
      heparin (UFH) with protamine and measuring AXa activity with the two chromogenic
      assays. An AXa activity was still measurable with Coamatic Heparin after
      neutralization, thus strongly suggesting that dextran sulfate dissociates
      protamine/heparin complexes. We conclude that Coamatic Heparin assays should be
      avoided when measuring AXa activity in plasma samples immediately after protamine
      infusion, as inaccurate results may lead to inadequate management of heparin
      reversal.

PMID- 14693176
TI  - Measurement of warfarin in plasma by high performance liquid chromatography
      (HPLC) and its correlation with the international normalized ratio.
AB  - The measurement of plasma warfarin is required to investigate non-compliance,
      resistance to anticoagulation, drug metabolism and pharmacokinetic. Methods so
      far described are based on extraction of warfarin from plasma followed by
      reversed-phase HPLC. Extraction is the crucial step and may be performed in
      liquid- or solid-phase. The latter requires the preparation of columns, which
      makes the procedure variable. We investigated the suitability of the ready-for
      use commercial cartridges for sample preparation. The method displayed between
      run CV of 11.8%. Recovery was 99%. The coefficients of correlation between
      warfarin concentration in 50 patients and weekly dosage or INR were 0.55
      (p<0.0001) or 0.25 (p=0.079).

PMID- 14693177
TI  - Enzyme immunoassay for measurement of murine plasminogen activator inhibitor-1,
      employing a specific antibody produced by the DNA vaccine method.
AB  - We developed a sensitive immunoassay to determine the concentration of mouse
      plasminogen activator inhibitor-1. The assay was a non-competitive sandwich
      enzyme-linked immunosorbent assay (ELISA) based on the production of a specific
      polyclonal antibody against mouse plasminogen activator inhibitor type-1 (PAI-1)
      used both as a trapping and detecting antibody. This antibody was raised in a
      rabbit by direct introduction of the expression vector plasmid DNA encoding mouse
      PAI-1, instead of conventional immunization with the purified protein. The
      standard curve was constructed with a recombinant glutathione S-transferase (GST)
      mouse PAI-1 fusion protein (GST-mPAI-1) and dose-response of the assay was linear
      for GST-mPAI-1 between 6.25 and 100 pM. In order to assess the consistency of the
      assay, we measured PAI-1 antigen in normal mouse pooled plasma several times. We
      found that the intra-assay and inter-assay coefficients of variation (CV) were
      4.8% and 9.2%, respectively, indicating that the ELISA would be sufficiently
      repeatable and reproducible. In this assay, lipopolysaccharide (LPS)-injected
      mice showed substantially higher levels (22-fold) of plasma PAI-1 antigen than
      did control mice (12.5+/-2.4 vs. 0.58+/-0.16 nM), similar to results reported
      elsewhere. Taken together, the DNA vaccine method is extremely useful for
      preparing specific antibodies against mouse PAI-1, which can be utilized to
      establish the ELISA and analyze the profile of PAI-1 distributions in mice under
      various conditions. This approach might also be useful for immunological
      investigation of other coagulation factors and related proteins.

PMID- 14693178
TI  - Discontinuous residues of factor IX constitute a surface for binding the anti
      factor IX monoclonal antibody A-5.
AB  - Anti-human factor IX monoclonal antibody, A-5 (Mab A-5), has been widely used in
      structure-function studies for factor IX. Mab A-5 recognizes the catalytic domain
      of human factor IX (FIX). Regions important for Mab A-5 binding have previously
      been localized to the amino terminus of the heavy chain of factor IX,
      encompassing amino acid residues 181-310 [Blood (74) 971]. We have selected 20
      positions in this region for alanine-scanning mutagenesis. We found that Mab A-5
      failed to react with the recombinant factor IX mutants with substitutions at
      positions 228 and 252. Mab A-5 also reacted to a lesser extent to FIXD276A
      (factor IX with alanine substitution for aspartic acid at residue 276) and
      FIXK201A/D203A (double alanine substitutions at residues 201 and 203). The
      apparent dissociation rate constants (K(D)) in binding Mab A-5 were 6.0 x 10(-9),
      1.4 x 10(-8) and 2.0 x 10(-8) M, for wild-type FIX, FIXK201A/D203A and FIXD276A,
      respectively. The increased K(D) values of the two FIX mutants are mainly owing
      to the increased dissociation rates. These affected residues constitute a surface
      opposite from the factor VIIIa binding surface. We conclude that the epitope for
      Mab A-5 is on a surface composed of residues 228, 252, 276, and 201 or 203. This
      surface, which may not be important for factor VIII binding, contains a strong
      antigenic region on factor IX.

PMID- 14693179
TI  - Expression of type-1 plasminogen activator inhibitor in the kidney of diabetic
      rat models.
AB  - INTRODUCTION: Intrarenal coagulation and fibrinolysis are thought to be involved
      in the pathogenesis of diabetic nephropathy. However, gene expression of
      fibrinolytic factors in diabetic nephropathy has not been clearly defined.
      Therefore we determined the gene expression of fibrinolytic factors in the
      kidneys of diabetic rats. MATERIALS AND METHODS: As a model of type1 diabetes
      male Sprague-Dawley rats were used. They were divided into three groups: control,
      streptozotocin (STZ)-induced diabetic, and insulin-treated diabetic. Otsuka Long
      Evans Tokushima Fatty (OLETF) rats were used as a model of type 2 diabetes; and
      Long-Evans Tokushima Otsuka (LETO) rats, as the control. Renal gene expressions
      of type-1 plasminogen activator inhibitor (PAI-1), tissue-type PA (tPA), and
      urokinase-type PA (uPA) were examined by real-time PCR. Localization of PAI-1
      mRNA was investigated by in situ hybridization. RESULTS: Renal PAI-1 mRNA levels
      (versus control) were increased by 60-80% in STZ-induced diabetic rats (10 days
      or 3 weeks post STZ injection); and insulin treatment reduced this increased
      expression to the control level. In OLETF rats (38 weeks old), the renal PAI-1
      mRNA level was 2.5-fold higher than that in age-matched LETO rats. Both tPA and
      uPA mRNA levels were significantly lower than those in LETO rats. PAI-1 mRNA was
      observed in intraglomerular cells and tubular epithelial cells of both models.
      CONCLUSIONS: Renal PAI-1 gene expression is up-regulated in both type 1 and type
      2 diabetic rats, and changes in gene expressions of fibrinolytic factors may play
      important roles in the development and pathogenesis of diabetic nephropathy.

PMID- 14693180
TI  - Validation of a novel tissue factor assay in experimental human endotoxemia.
AB  - BACKGROUND: Nuclear factor kappa B (NF-kappa B) activation and tissue factor (TF)
      expression may contribute to lethality in sepsis. Inappropriate in vivo
      expression of TF is likely responsible for fibrin deposition in sepsis-associated
      disseminated intravascular coagulation (DIC). Clinical assessment of TF
      expression has remained a major challenge. No point-of-care assays are currently
      available to measure the level of TF activity in whole blood. The current study
      examined the suitability of the TiFaCT assay as a point-of-care assay to detect
      TF expression. METHODS: 30 healthy male volunteers received 2 ng/kg of LPS.
      Tissue factor-dependent coagulation was quantified with a novel assay called
      tissue factor clotting time (TiFaCT), and by measurement of activation markers of
      downstream coagulation. RESULTS: Ex vivo addition of anti-TF antibodies to blood
      slightly increased clotting times at 0-24 h (p<0.01) indicating that some tissue
      factor activity was present in whole blood at any time. LPS bolus infusion
      decreased TiFaCT clotting time by -23% compared to baseline (p<0.01), when in
      vivo clotting increased, as demonstrated by a 10-fold increase in prothrombin
      fragment levels (F1+2). Ex vivo incubation with LPS considerably shortened TiFaCT
      (from 1000s to 400s as compared to control incubation; p<0.01). This effect was
      blunted at 2-4 h after LPS infusion (i.e. the time of monocytopenia), but twofold
      enhanced 24 h after LPS challenge (p<0.01). CONCLUSIONS: In summary, the TiFaCT
      assay was validated in our in vivo model of LPS-induced coagulation. It detected
      minute quantities of circulating TF even at baseline. TiFaCT is shortened at
      times of in vivo thrombin generation.

PMID- 14693181
TI  - PT G20210A, factors V G1691A and 1299 His-Arg mutations and tamoxifen-associated
      thromboembolism in patients with breast cancer.

PMID- 14693182
TI  - Visual working memory for image statistics.
AB  - To define the role of statistical features of images in visual working memory, we
      compared the ability of subjects (N=6) to identify changes in arrays of black and
      white checks when these changes altered some aspect of their statistical
      structure, versus when these changes did not. Alteration of luminance statistics
      or local higher-order statistics improved performance, but alteration of the
      degree of bilateral symmetry did not. The dependence of performance on the degree
      of statistical change indicated that statistical information was represented in a
      graded, rather than categorical, fashion.

PMID- 14693183
TI  - Combining depth cues: effects upon accuracy and speed of performance in a depth
      ordering task.
AB  - Two experiments investigated how the number of available depth cues affected the
      speed and accuracy of depth-ordering judgements. A series of textured tiles was
      presented on a computer monitor, with relative depths defined by combinations of
      contrast, blur and interposition. Subjects were required to move a mouse pointer
      inside each tile in turn, starting with the tile that appeared nearest, clicking
      on each. Accuracy of depth-ordering was much higher than chance in all
      conditions, though performance using the interposition cue alone was worse than
      in all other conditions. The only difference in reaction time in different cue
      conditions was in the time elapsed before the first-click. Subjects responded
      substantially faster when three depth cues were present (0.84 s) than when only
      one depth cue was present (1.41 s). The improvement in reaction time with cue
      numerosity is consistent with probability summation between cues extracted by
      independent processes.

PMID- 14693184
TI  - Spatial-scale interaction in human stereoscopic vision in response to sustained
      and transient stimuli.
AB  - We investigated temporal properties of stereopsis at different spatial scales in
      dynamic random-dot stereograms (DRS) consisting of (i) the repeated presentation
      of two image pairs (i.e. sustained presentation) and (ii) single presentations of
      two image pairs (transient presentation). In dense stereograms perception of
      depth is possible if the levels of interocular correlation are above a certain
      threshold. Therefore, detection of correlation is an important step in
      stereopsis. Across different experiments, we varied the level of interocular
      correlation as a function of time by alternating correlated and un/anticorrelated
      random-dot stereograms. Also, we varied their spatial scale (coarse, fine and
      alternating between coarse and fine). The presence of stereopsis was examined
      using a forced-choice depth detection task. For both sustained and transient
      presentations of the stimuli, the results show that (i) stereopsis has similar
      temporal properties at coarse and fine spatial scales; (ii) interaction between
      spatial scales depends on their relative sizes. The results indicate a strong
      inhibitory influence of rivalry at a coarse scale on stereopsis at a fine scale,
      and just a weak inhibitory influence of rivalry at a fine scale on stereopsis at
      a coarse scale. This study provides experimental evidence for a hierarchical
      organisation of spatial scales in human stereoscopic vision based on neural
      interaction instead of vergence eye movements.

PMID- 14693185
TI  - Spatial distortions and processing latencies in the onset repulsion and Frohlich
      effects.
AB  - In the Frohlich illusion, the first position of a moving target is mis-localized
      in the direction of motion. In the onset repulsion effect, the opposite error
      occurs. To reconcile these conflicting error patterns, we improved previous
      methods by using natural pointing movements and a large range of target
      velocities. Displacement was found to increase in the direction of motion, but
      the linear function relating velocity and displacement was shifted opposite to
      the direction of target motion. The results suggest that onset localization may
      be determined by two independent factors: first, an (attentional) delay that
      accounts for the increase of displacement in the direction of motion with
      increasing velocity. This delay is visible in motor and probe judgments and
      explains the Frohlich illusion. Second, motor judgments are offset opposite to
      the direction of target motion. This bias is unique to motor judgments (pointing)
      and may be partially explained by attentional repulsion.

PMID- 14693186
TI  - Dynamic aspects of accommodation: age and presbyopia.
AB  - There has been no comprehensive study involving each of the primary dynamic
      components of accommodation in the same cohort as related to age and presbyopic
      onset; furthermore, the current findings are equivocal. Dynamic monocular
      components of accommodation (latency, time constant, peak velocity/amplitude
      relationship, and microfluctuations) were assessed objectively using an infrared
      optometer within the linear region of accommodation in 30 visually-normal human
      subjects aged 21-50 years. The time constant and the peak velocity/amplitude
      relationship did not change with age. However, latency progressively increased,
      and microfluctuation amplitude and frequency progressively decreased, with
      increasing age. The invariance in time constant suggests that the gross
      biomechanical aspects of the lens and related structures in the remaining linear
      region are relatively unaffected by age. In contrast, the decrease in
      microfluctuation activity with age suggests more subtle alterations in the
      biomechanical aspects of the lens to these very small perturbations, such as a
      response amplitude non-linearity. With respect to neurologic control, the
      progressive latency increase suggests a processing delay of the blur input, and
      this is consistent with age-related changes in reaction time measures. The lack
      of any age-related changes in the peak velocity/amplitude relationship implies
      normalcy of central and peripheral neuromotor control, as well as grossly normal
      first-order lens biomechanics, in this linear response region. The results are
      consistent with the Hess-Gullstrand theory of presbyopia.

PMID- 14693187
TI  - The induced Roelofs effect: two visual systems or the shift of a single reference
      frame?
AB  - Cognitive judgments about an object's location are distorted by the presence of a
      large frame offset left or right of an observer's midline. Sensorimotor
      responses, however, seem immune to this induced Roelofs illusion, with observers
      able to accurately point to the target's location. These findings have
      traditionally been used as evidence for a dissociation of the visual processing
      required for cognitive judgments and sensorimotor responses. However, a recent
      alternative hypothesis suggests that the behavioral dissociation is expected if
      the visual system uses a single frame of reference whose origin (the apparent
      midline) is biased toward the offset frame. The two theories make qualitatively
      distinct predictions in a paradigm in which observers are asked to indicate the
      direction symmetrically opposite the target's position. The collaborative
      findings of two laboratories clearly support the biased-midline hypothesis.

PMID- 14693188
TI  - Eye-position dependence of torsional velocity during interaural translation,
      horizontal pursuit, and yaw-axis rotation in humans.
AB  - The translational vestibulo-ocular reflex (tVOR) stabilizes an image on the fovea
      during linear movements of the head. It has been suggested that the tVOR may
      share pathways with the pursuit system. We asked whether the tVOR and pursuit
      would be similar in their behavior relative to Listing's Law. We compared
      torsional eye velocity as a function of vertical orbital position during
      interaural translation, pursuit, and yaw-axis rotation. We found that the eye
      position-dependence of torsion was similar during translation and pursuit, which
      differed from that during yaw-axis rotation. These findings further support a
      close relationship between the mechanisms that generate pursuit and the tVOR.

PMID- 14693189
TI  - A neurodynamical cortical model of visual attention and invariant object
      recognition.
AB  - We describe a model of invariant visual object recognition in the brain that
      incorporates feedback biasing effects of top-down attentional mechanisms on a
      hierarchically organized set of visual cortical areas with convergent forward
      connectivity, reciprocal feedback connections, and local intra-area competition.
      The model displays space-based and object-based covert visual search by using
      attentional top-down feedback from either the posterior parietal or the inferior
      temporal cortex (IT) modules, and interactions between the two processing streams
      occurring in V1 and V2. The model explains the gradually increasing magnitude of
      the attentional modulation that is found in fMRI experiments from earlier visual
      areas (V1, V2) to higher ventral stream visual areas (V4, IT); how the effective
      size of the receptive fields of IT neurons becomes smaller in natural cluttered
      scenes; and makes predictions about interactions between stimuli in their
      receptive fields.

PMID- 14693191
TI  - Increases in nerve growth factor immunoreactivity in the submandibular gland, but
      not in the parotid gland, of the rat following sympathetic denervation.
AB  - The effect of sympathetic denervation on nerve growth factor (NGF)
      immunoreactivity in the submandibular and parotid glands of adult female rats
      using a two-site, enzyme-linked immunosorbent assay was investigated. Unilateral
      sympathetic denervation through the avulsion of the superior cervical ganglion
      resulted in elevated levels of total amounts (decreased from 40-20%) and
      concentrations (decreased from 45-32%) of NGF in the submandibular glands, but
      not in the parotid glands, on the operated side 7-28 days post-operatively.
      Sympathetic decentralisation had no effect. The present findings support the
      hypothesis that increased levels of NGF play an important part in the increased
      activity of the acetylcholine-synthesising enzyme, choline acetyltransferase, in
      the rat submandibular gland following sympathetic denervation.

PMID- 14693192
TI  - Human salivary gland-specific daily variations in histatin concentrations
      determined by a novel quantitation technique.
AB  - Histatins constitute a distinct family of human salivary antimicrobial peptides,
      of which histatins 1, 3 and 5 are the most abundant. To evaluate salivary gland
      specific differences in histatin secretion, we used the recently developed
      histatin-zinc precipitation method to quantify histatins and to assess daily
      variations in secretions. Stimulated pure secretions from parotid glands (HPS)
      and submandibular/sublingual glands (SMSL) were collected from 10 different
      subjects at four different times of the day (9:35 a.m.; 12:40 p.m.; 2:50 p.m. and
      5:00 p.m.). Zinc precipitation and subsequent reversed phase HPLC analysis were
      performed to determine concentrations of histatins 1, 3 and 5 with reference to
      purified histatin standards. Both HPS and SMSL secretions displayed daily
      variations in histatin concentrations. HPS values showed a maximum at mid-day and
      SMSL samples showed a maximum in the morning. Mean daily histatin concentrations
      were almost three fold higher in SMSL than in HPS. Mean histatin 1, 3 and 5
      concentrations in HPS from 10 subjects ranged from 0.7 to 2.8, 0.6 to 4.3 and 1.0
      to 4.3mg%, respectively. The corresponding means in SMSL were 2.8-12.2, 1.5-7.5
      and 2.6-9.0mg%, respectively. Remarkably, although histatins constitute only 3
      10% of total protein in these secretions, an almost perfect correlation between
      total protein and total histatin concentrations was observed for both glands.
      Despite a broad range in histatin concentrations between individuals, this study
      demonstrated a hitherto unidentified daily variation in histatin concentrations
      in HPS and SMSL secretions and a differential expression pattern which might have
      functional implications.

PMID- 14693193
TI  - A standardised protocol for the quantification of lactate dehydrogenase activity
      in saliva.
AB  - The literature about salivary lactate dehydrogenase (LDH) activity shows
      different results, conditioned by the diversity of methods used for sampling,
      handling and analysis. OBJECTIVES: The aim of this study was to design a protocol
      for quantifying salivary lactate dehydrogenase activity. METHODS: Whole saliva
      samples were collected from 100 healthy volunteers by chewing a roll of cotton.
      Lactate dehydrogenase activity determinations were made with the Cobas Mira Plus
      II autoanalyser using the recommendations proposed by the International
      Federation of Clinical Chemistry (IFCC) and the French Society of Clinical
      Biology (SFBC). Samples were stored at room temperature (20-22 degrees C), in the
      refrigerator (4 degrees C) and freezer (-20 degrees C). The correction capacity
      of the autoanalyser was evaluated by making serial determinations in samples of
      saliva diluted in water. RESULTS: The frozen samples, but not those stored in the
      refrigerator or at room temperature, showed an important degradation of lactate
      dehydrogenase activity. When the samples were diluted in water, the lactate
      dehydrogenase activity varied substantially with the International Federation of
      Clinical Chemistry method after correction, but not when using the French Society
      of Clinical Biology method. CONCLUSION: For salivary lactate dehydrogenase
      activity quantification we suggest that samples be stored at 4 degrees C and
      analyse with the French Society of Clinical Biology method.

PMID- 14693194
TI  - Immunocompetent cells in the pulp of human deciduous teeth.
AB  - This immunohistological study sought to determine how the distribution and
      density of various immunocompetent cells change in the pulp of human deciduous
      teeth during the process of physiological root resorption. Forty-three extracted
      deciduous teeth at various stages of resorption were subjected to
      immunoperoxidase staining with the use of antibodies directed to HLA-DR, CD68,
      factor XIIIa and lymphocyte subsets. In intact deciduous teeth (group 0), all
      types of cells examined, except for CD20+ B lymphocytes, were detected. In teeth
      in which resorption was less than 1/3 of the root length (group 1), all types of
      cells showed a statistically significant increase compared with group 0 (P<0.05;
      Mann-Whitney's U-test). HLA-DR+, CD68+, and factor XIIIa+ cells with a dendritic
      profile kept their distribution in the periphery of the pulp, and oval and round,
      newly recruited macrophages accumulated in the central portion of the pulp and
      near the resorption sites. In teeth where resorption was 1/2 to 2/3 (group 2),
      all the cell types increased further. Aggregations of HLA-DR+, CD68+, and factor
      XIIIa+ cells were frequently seen in the central portion of the pulp, and T and B
      lymphocytes occasionally formed some clusters. Comparisons with group 1 revealed
      that the density of these cells, except for CD20+ cells, showed significant
      increases (P<0.05; Mann-Whitney's U-test). These results provided evidence
      showing that immunocompetent cells of deciduous tooth pulp increase with the
      progress of physiological root resorption, suggesting that immunocompetency of
      deciduous teeth is altered by this process.

PMID- 14693195
TI  - Calbindin D-28k distribution in odontoblasts underneath tertiary dentine in human
      carious teeth.
AB  - OBJECTIVE: The aim of this study was to examine the calbindin D-28k
      immunoreactivity in carious teeth to know whether this protein may have a
      function in tertiary dentine formation. METHODS: Human extracted teeth with or
      without carious lesions were immersion-fixed with Zamboni fixative, demineralized
      in 4.13% EDTA solution (pH 7.4), frozen-sectioned, and processed for calbindin
      immunoreactivity and hematoxylin-eosin stain. The intensity of the immunostaining
      was evaluated by quantitative densitometry. RESULTS: In intact teeth, numerous
      odontoblasts were aligned underneath the secondary dentine and their cell bodies
      showed the immunoreactivity. In carious teeth, tertiary dentine had poor- or rich
      tubular patterns under the carious lesion. Underneath the tubule-poor tertiary
      dentine, distinct odontoblasts could not be seen at the central site. However,
      some cells with a flat appearance were located at this site and were
      immunonegative for calbindin D-28k. On the other hand, columnar odontoblasts were
      seen at the peripheral site, and their cell bodies and processes showed strong
      immunoreactivity. Underneath the tubule-rich tertiary dentine, columnar
      odontoblasts were abundantly distributed, and the strong immunoreactivity was
      observed in their cell bodies and processes. The immunoreactivity in odontoblasts
      underneath the tertiary dentine with poor or rich tubular pattern was more
      intense than that for the secondary dentine in intact teeth (P<0.05). On the
      other hand, the intensity of the immunoreactivity in odontoblasts was similar
      underneath the secondary dentine in intact and carious teeth. CONCLUSIONS: The
      present study demonstrated that calbidin D-28k was actively synthesised by
      odontoblasts under the carious lesion. These findings may suggest that this
      protein plays an important role in the tertiary dentine formation.

PMID- 14693196
TI  - SEM observations of Retzius lines and prism cross-striations in human dental
      enamel after different acid etching regimes.
AB  - OBJECTIVE AND DESIGN: Sectioned and ground enamel surfaces need to be etched with
      acid in order for the enamel structure to be exposed for study in the SEM. In the
      present study Retzius lines and prism cross-striations were observed in variably
      ground specimens after etching with nitric acid of different concentrations (0.1,
      1, 2.5 and 5%) and for different time periods (15, 30, 45, 90 and 180s). The aims
      were to improve our interpretation of these structures and to find the best
      etching regime. RESULTS AND CONCLUSIONS: Retzius lines in the superficial enamel
      were more readily exposed than Retzius lines in deeper parts of the enamel. The
      former showed discontinuity defects that facilitated their identification, while
      the latter lacked such defects. Few deep Retzius lines were exposed and could
      first be identified with certainty after etching for 30s in 1% acid. The
      structural and compositional basis for the visibility of deep Retzius lines may
      be subtle and difficult to identify. Scratches from the sectioning/grinding
      procedures may disturb their identification, but in general the grinding
      procedure was of minor importance for interpretation of enamel structure. Prism
      cross-striations were more readily exposed with the three stronger acid
      concentrations than with the weakest. They appeared as alternate light and dark
      bands, with a lower crystal concentration in the dark bands. No clear association
      with the prism varicosities/undulations was found. Etching with 1% nitric acid
      for 30s seems to be a good compromise for the study of Retzius lines and prism
      cross-striations.

PMID- 14693197
TI  - The sources of laser Doppler blood-flow signals recorded from vital and root
      canal treated teeth.
AB  - OBJECTIVES: The aim was to determine the strength of signals derived from the
      dental pulp and those from the surrounding tissues in human teeth using the laser
      Doppler flowmetry (LDF). METHODS: Twenty-six vital teeth (13 experimental and 13
      controls) from 12 patients were used. Experimental teeth had root canal treatment
      in a single visit and their healthy antimeres were controls. Blood flow
      measurements were made before and after local anaesthesia, after root canal
      preparation, following root canal filling and coronal restoration. RESULTS:
      Perfusion unit (PU) values recorded from empty pulp chamber were determined to be
      only 30% lower than the values recorded before anaesthesia from the experimental
      intact teeth. When the measurements in the group were compared with each other
      the values of variation in the both groups were not statistically significant.
      The variation between the groups when the measurement values before anaesthesia,
      10min after anaesthesia and after coronal restoration were compared, it was not
      statistically significant (P>0.05). The variation between the groups after
      preparation and root canal filling in their values of measurements was important
      statistically (P<0.05). The measurement values of the study group were lower than
      that of the control group. CONCLUSIONS: In pulpal, LDF a major portion of the
      signal comes from tissues other than pulp. Without taking precautions (such as
      rubber-dam application) in pulp blood flow measurements, the results may be
      inconsistent.

PMID- 14693198
TI  - Periodontal regeneration of transplanted rat molars after cryopreservation.
AB  - The effects of cryopreservation on periodontal regeneration of transplanted rat
      molars were investigated histologically and histochemically in rats. Bilateral
      first and second maxillary molars of 4-week-old Wistar rats were gently extracted
      and transplanted into the abdominal subcutaneous connective tissue immediately or
      after cryopreservation in liquid nitrogen overnight. Donor teeth were slowly
      frozen by a rate-controlling freezer (program freezer) using 5% dimethylsulfoxide
      (DMSO) and 6% hydroxyethyl starch (HES) as cryoprotectants. One-four weeks after
      transplantation, they were carefully excised with the surrounding tissues.
      Regeneration of acellular cementum, periodontal ligament, and alveolar bone were
      observed 2 weeks after immediate transplantation. The pulp was repaired by the
      ingrowth of granulation tissue from the root apex followed by the formation of
      calcified tissue. The regenerated periodontal ligament was positive for alkaline
      phosphatase (ALP). Small or mononuclear tartrate resistant acid phosphatase
      (TRAP) positive cells were scattered on the newly formed alveolar bone and on the
      hard tissue in the pulp, but there was no external or internal progressive root
      resorption at 4 weeks. Cryopreserved teeth had acellular cementum with a rough
      surface at 1 week, but with the increase of cementoblasts and the appearance of
      periodontal ligament and alveolar bone, the surface became smooth at 3 weeks.
      Epithelial rests of Malassez (ERM) also revived. After regeneration of the
      periodontal tissues at 4 weeks, there was no evidence of root resorption.
      Although the process proceeded slowly, the cryopreserved teeth showed the
      periodontal regeneration substantially similar to that of the immediately
      transplanted teeth without progressive root resorption, indicating that they
      could be applicable for clinical use.

PMID- 14693200
TI  - A comparison of resins for embedding teeth, with special emphasis on adaptation
      to enamel surface as evaluated by scanning electron microscopy.
AB  - OBJECTIVE: Eight commercially available resins, Epoxy Embedding Medium ("Epon"),
      Spurr, Epofix, Epo-Kwick, Epo-Thin, Technovit 9100 New, Unicryl, and Vestopal W,
      all intended for embedding specimens for microscopy, were tested and compared for
      binding and adaptation to the enamel surface of human third molar crowns that had
      been embedded in them. DESIGN: After sectioning, grinding and acid etching, the
      specimens were observed in the SEM. The presence or absence of a gap between
      enamel and resin was recorded together with the width of the gap, when present.
      RESULTS: A pilot study, where gaps were observed before and after etching,
      indicated that the etching did not widen the gap appreciably. The resins could be
      divided into three groups according to gap width: "Epon" and Spurr performed best
      with a mean gap width of only 0.6microm. Vestopal W, Epofix, Epo-Kwick, Epo-Thin,
      and Technovit 9100 New constituted a group of medium performance with mean gap
      widths of 2.3, 3.4, 3.8, 3.9 and 3.9microm, respectively. Less satisfactory
      performance was observed for Unicryl, with a mean gap width of 7.4microm.
      CONCLUSIONS: It is concluded that "Epon" and Spurr should be chosen for high
      quality embedding of undecalcified teeth, while Epo-Kwick is an acceptable
      alternative if a faster procedure is needed.

PMID- 14693199
TI  - The expression of osteoprotegerin and the receptor activator of nuclear factor
      kappa B ligand in human periodontal ligament cells cultured with and without
      1alpha,25-dihydroxyvitamin D3.
AB  - The receptor activator of nuclear factor kappa B ligand (RANKL) and its decoy
      receptor, osteoprotegerin (OPG), are important bone metabolism molecules, which
      directly control osteoclastogenesis. Periodontal ligament (PDL) cells play a
      vital role in maintaining the homeostasis of periodontal tissues, releasing
      cytokines to affect bone metabolism. The purpose of this study was to investigate
      the expression of OPG and RANKL in cultured human periodontal ligament cells
      (hPDLCs) derived from permanent teeth and the expression change after stimulation
      by 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)vitD(3)), a kind of bone
      resorption promoter. HPDLCs were cultured in the presence or absence of 10(-8)M
      1alpha,25(OH)(2)vitD(3) in vitro. The expression of mRNA for OPG and RANKL in
      hPDLCs during 6 days' culture was examined using semi-quantitative reverse
      transcription-polymerase chain reaction (RT-PCR). The level of secreted OPG
      protein in the culture medium during 6 days' culture was detected by enzyme
      linked immunoabsorbent assay (ELISA). The result showed that OPG and RANKL were
      expressed by hPDLCs. OPG expression was down-regulated by 10(-8)M
      1alpha,25(OH)(2)vitD(3) in a time-dependent manner, while RANKL mRNA was up
      regulated. The ratio of OPG/RANKL was decreased. In conclusion, our findings
      suggest that hPDLCs may regulate the alveolar bone metabolism through the
      OPG/RANKL system.

PMID- 14693201
TI  - Immunocytochemical demonstration of estrogen receptor beta in human periodontal
      ligament cells.
AB  - Two transcription associated estrogen receptor (ER) subtypes have been identified
      and named ERalpha and ERbeta. In the present study we investigate the expression
      of these ER subtypes in cultured human periodontal ligament (PDL) cells by
      immunocytochemistry. ERbeta immunoreactivity was observed in the nuclei of about
      40% of the PDL cells, while no ERalpha immunoreactivity was detected. In human
      breast cancer MCF-7 cells, serving as positive controls, both ERalpha and ERbeta
      immunoreactivities were demonstrated. No immunoreactivity was observed after
      omission of the primary antibodies. This study suggests that estrogen acts on
      gene transcription preferentially via ERbeta in human PDL cells.

PMID- 14693203
TI  - Quantitative analysis of the mineral content of sound and carious primary dentine
      using BSE imaging.
AB  - Backscattered electron-scanning electron microscope (BSE-SEM) imaging has been
      recommended as a reliable tool to quantify the mineralisation state of calcified
      tissues and is commonly used in bone studies. The aim of this study is to
      investigate the use of BSE imaging to quantitatively analyse the mineral content
      of sound and carious dentine. Eight primary molars with untreated carious dentine
      were embedded in resin, axially sectioned and fine polished for this study. The
      BSE images were from a solid-state detector in an SEM operating at 1.5Torr gas
      pressure. BSE images of a number of different elements and compounds with atomic
      number ranged from 4 to 26 were analysed prior to the test to calibrate the
      experimental conditions and an enamel-carbon block. The mineral analysis was
      based on the change in BSE intensity (measured in graylevels). The results showed
      that variation in graylevels accurately represented difference in the atomic
      number and BSE coefficient of the test materials. The mineral content of sound
      primary dentine in the most regions was 59.3+/-5.5 wt.%, but it decreased
      gradually to be just 41.82+/-6.74 wt.% adjacent to the pulp. The carious dentine
      showed a marked reduction in mineral content which proceeded progressively toward
      the cavity floor, in which the minimum value of less than 10 wt.% was normally
      found in the outer layer of the lesion. The results show that BSE imaging is a
      simple and reliable technique that can be used to quantify the mineral content of
      sound and carious dentine. More importantly the variable pressure SEM offers an
      approach to minimize the impact of dehydration on carious dentine specimens.

PMID- 14693202
TI  - Reduction in dentin permeability using mildly supersaturated calcium phosphate
      solutions.
AB  - Treatments that obturate dentin tubules have been used for reducing dentin
      hypersensitivity. The objective of this study was to determine the effects of
      multiple treatments with a mildly supersaturated calcium phosphate solution on
      the hydraulic conductance (Lp) of partially occluded dentin discs in vitro. The
      treatment solution contained 6.5 mmoll(-1) each of calcium and phosphate, 0.25
      mmoll(-1) fluoride, 30 mmoll(-1) KCl, and 50 mmoll(-1) HEPES buffer (pH adjusted
      to 7.0). The mean baseline Lp (in microlcm(-2)min(-1) H(2)O cm(-1)) was 0.108+/
      0.041 (mean +/- S.D.; n=9, microlcm(-2)min(-1) H(2)O cm(-1) = 10.20 microlcm(
      2)min(-1)KPa(-1)) and after five consecutive treatments, the mean relative Lp,
      presented as percentage of baseline, were 71+/-11, 58+/-10, 46+/-18, 40+/-14, and
      25+/-10, respectively. The Lp values of the baseline and treatment groups were
      significantly (P<0.05) different. Consecutive treatments appeared effective in
      further reducing Lp of dentin discs.

PMID- 14693204
TI  - Cbfa1 couples chondrocytes maturation and endochondral ossification in rat
      mandibular condylar cartilage.
AB  - Core binding factor a1 (Cbfa1) is a crucial transcription factor for osteoblasts
      differentiation and chondrocytes maturation in embryonic skeletal genesis, but
      little is known about its function in mandibular condylar growth. The aim of this
      study was to determine the temporal and spatial pattern of Cbfa1 expression in
      condylar cartilage during natural growth. Mandibular condyles were harvested from
      50 female Sprague-Dawley rats at age of 38, 42, 49, 56 and 65 days. Alcian blue
      and PAS staining was used for histological analysis. Type A antibody raised
      against Cbfa1 isoform II was observed in the pre-hypertrophic and hypertrophic
      chondrocytes in condylar cartilage, and in the mature osteocytes in trabecular
      bone. Type B antibody raised against 17 aa sequence present after the Runt domain
      was detected in tartrate resistant acid phosphatase (TRAP) positive osteoclasts
      in the erosive front of cartilage, and also in the osteoblasts on the sub
      chondral bone surface. In situ hybridisation was carried out with a probe
      containing a fragment in exon 8 of the cDNA. Cbfa1 transcripts were localised in
      the osteoblasts and chondrocytes, but not in osteoclasts. Quantitative analysis
      demonstrated that both types of Cbfa1 proteins reached their maximum level on day
      56, which coincided with the terminal maturation of hypertrophic chondrocytes and
      the aggregation of mineralisation deposits in extracellular matrix. These results
      suggest that Cbfa1 is a master gene controlling the functions of all the skeletal
      cell lineages by synthesising different functional isoforms. Furthermore, Cbfa1
      couples the process of chondrocytes maturation, extracellular matrix
      mineralisation and degradation, as well as osteoblasts invasion during
      endochondral bone formation. Beyond its function on embryonic development, Cbfa1
      regulates the postnatal growth of mandibular condyle.

PMID- 14693205
TI  - Expression of tropoelastin in human periodontal ligament fibroblasts after
      simulation of orthodontic force.
AB  - The ability of elastic fibers to respond to mechanical stimuli suggests that they
      play a central role in physiological adaptation to external stimuli including
      application of orthodontic force. The purpose of this study was to examine the
      effect of external pressure simulating orthodontic force on tropoelastin gene
      expression in cultured human periodontal ligament fibroblasts (hPDLF). External
      pressure simulation was achieved by centrifugation for 10, 30, 60, 90 and 120 min
      of hPDLF in a horizontal microplate rotor. Semi-quantitative RT-PCR analysis of
      tropoelastin mRNA was performed and beta-actin was used as an internal invariant
      control. While centrifugal force on mRNA levels of beta-actin showed almost no
      change, the mRNA levels of tropoelastin increased significantly to a peak level
      of more than four-fold after 30 min. Thereafter, at 60 min, the mRNA levels
      remained at more than three-fold. After 90 min, mRNA levels decreased to control
      levels. The finding that no changes in mRNA levels of beta-actin occurred during
      the first 90 min of centrifugation validates its use as an invariant control gene
      in such an experimental model. This study demonstrated that tropoelastin is
      expressed in hPDLF and that the pressure caused significant time-dependent
      upregulation of the tropoelastin gene. The responsiveness of the tropoelastin
      gene to force shows its possible clinical importance in orthodontic tooth
      movement. Further studies, however, are essential in order to learn whether the
      high expression of the gene in vitro will also be followed by corresponding
      protein synthesis and deposition in vivo in the extracellular matrix (ECM) of the
      periodontal ligament (PDL).

PMID- 14693206
TI  - Antioxidative vitamins decrease cytotoxicity of HEMA and TEGDMA in cultured cell
      lines.
AB  - OBJECTIVES AND METHODS: In a previous study it was postulated that toxicity of 2
      hydroxyethylmethacrylate (HEMA) and triethleneglycoldimethacrylate (TEGDMA) is
      based on oxidative metabolites. In this study the influence of antioxidative
      vitamins (including uric acid) on the toxicity of HEMA or TEGDMA was tested.
      Toxicity of HEMA and TEGDMA was determined in rat alveolar epithelial L2, human
      malignant A549, and human fibroblast-like 11Lu cells by inhibition of methionine
      incorporation (as a marker of protein synthesis inhibition) and by determination
      of glutathione depletion, as well as by measurement of GSSG increase. RESULTS:
      Toxicity of the composite components HEMA and TEGDMA was demonstrated by GSH
      depletion as the most sensitive method. Five hundred micromoles per litre Vitamin
      C or 250 micromol/l Vitamin E were mostly able to decrease toxicity of HEMA and
      TEGDMA in the cell lines tested. In addition, 250 micromol/l Vitamin A was only
      effective in L2 cells impairing HEMA toxicity and 250 micromol/l uric acid
      impairing TEGDMA toxicity as assessed by decreased GSH depletion. In A549 cells
      only methionine incorporation inhibition but not GSH depletion was significantly
      affected. By contrast, in 11Lu cells methionine incorporation inhibition was not
      significantly changed, but GSH depletion was. CONCLUSIONS: The postulated
      mechanism of HEMA or TEGDMA toxicity based on radical metabolites is supported by
      the effectivity of the antioxidative substances tested in mitigating toxicity and
      by the greater susceptibility of the glutathione redox system as compared to
      protein synthesis inhibition in assessing toxicity.

PMID- 14693207
TI  - Soluble tumour necrosis factor receptors in synovial fluids from
      temporomandibular joints with painful anterior disc displacement without
      reduction and osteoarthritis.
AB  - The objective of this study was to detect soluble-form tumour necrosis factor
      receptors (sTNFRs) in temporomandibular joint (TMJ) synovial fluid aspirates, and
      to compare the sTNFR concentrations between painful anterior disc displacement
      without reduction and osteoarthritis (ADDwoR/OA) and asymptomatic TMJs. Synovial
      fluid was sampled from the superior TMJ cavity of 11 painful ADDwoR/OA cases
      (mean age: 36.9 years) and 10 asymptomatic females (mean age: 24.7 years) by
      diluted aspiration. The concentrations of sTNFR-I and -II in the synovial fluid
      were measured using human sTNFR-I and -II enzyme-linked immunosorbent assays. The
      total protein concentrations in synovial fluids were measured using a
      bicinchoninic acid protein assay kit. All data were normalised to the total
      protein concentration of each sample.Two-way factorial analysis of variance and
      post hoc multiple comparison revealed that: (1). mean normalised sTNFR-I and -II
      concentrations were higher in TMJ synovial aspirates from ADDwoR/OA patients than
      from healthy controls; (2). in the ADDwoR/OA patients and the healthy controls,
      the sTNFR-I concentration in TMJ synovial aspirates was higher than the sTNFR-II
      concentration; and (3). high TMJ synovial aspirate sTNFR-II seemed to be
      associated with less TMJ pain and a less restricted range of mouth opening in the
      ADDwoR/OA patients. The concentrations of sTNFRs in TMJ synovial fluid are higher
      in the presence of painful ADDwoR/OA, which could modulate intracapsular
      inflammation.

PMID- 14693208
TI  - Immunohistochemical analysis of Bcl-2 and Bax oncoproteins in rabbit
      craniomandibular joint.
AB  - The purpose of this study was to elucidate the expression of proto-oncogene Bcl-2
      (anti-apoptotic) and Bax (pro-apoptotic) in fibrocartilage of the disc and
      hyaline cartilage of the condyle in the rabbit craniomandibular joint (CMJ). Ten
      New Zealand white rabbit heads were used. Sections were processed by the
      immunohistochemical techniques using mouse anti-Bcl-2 and anti-Bax antibodies.
      Intensity levels of immunostaining in condylar cartilage were quantified by a
      computer-image system. Immunoreactivity for Bcl-2 was mainly observed in the
      cytoplasm of the reserve cell and chondrocytic cell layers. A mild heterogeneous
      Bax expression was detected in the cytoplasm of chondrocytes of the upper
      hypertrophic layer and a few cells of the chondrocytic layer. The cytoplasm of
      chondrocytes in the disc exhibited a high intensity for Bcl-2, while Bax activity
      was only sporadically observed. We have shown that Bcl-2 and Bax proteins are
      present in CMJ cartilage and their expression patterns suggest that these
      oncoproteins are involved in chondrocyte survival or death via apoptotic
      pathways.

PMID- 14693209
TI  - Saliva flow rate, total protein concentration and osmolality as potential markers
      of whole body hydration status during progressive acute dehydration in humans.
AB  - OBJECTIVE: To identify whether saliva flow rate, total protein concentration and
      osmolality are sensitive non-invasive markers of whole body hydration status, we
      compared changes in these parameters with changes in body mass during progressive
      acute dehydration. DESIGN: Twelve euhydrated males reported to the laboratory
      following an overnight fast and cycled on a stationary ergometer at 60% maximal
      oxygen uptake in an environmental chamber (30 degrees C and 70% RH) until
      progressive body mass loss (BML) of 1.1+/-0.0, 2.0+/-0.0 and 2.9+/-0.2%. After
      exercise, subjects were given a volume of carbohydrate electrolyte solution
      equivalent to 150% BML to consume within 1h. Unstimulated whole saliva samples
      were collected over a 2 min period into pre-weighed tubes at pre-exercise, 1.1,
      2.0 and 2.9% BML and then at 75, 135 and 195 min post-exercise. RESULTS: Saliva
      total protein concentration and osmolality increased and flow rate decreased
      (P<0.01) during dehydration. Saliva total protein concentration and osmolality
      correlated strongly with % BML during dehydration (mean r=0.97 and 0.94,
      respectively: P<0.01). The correlation for saliva total protein concentration
      with % BML was greater (P<0.05) than the correlation for saliva flow rate with %
      BML (mean r=-0.88: P<0.01) during dehydration. CONCLUSIONS: These data show that
      changes in saliva total protein concentration and osmolality, and to a lesser
      extent flow rate, are strongly associated with changes in body mass during
      progressive acute dehydration.

PMID- 14693210
TI  - Comparison of single and multiple sieve methods for the determination of
      masticatory performance.
AB  - In the majority of studies on masticatory performance, the degree of food
      breakdown has been determined by sieving the food with one or more sieves. The
      aim of the present study was to compare the results obtained with a single and a
      multiple sieve method, as these methods have never been compared. We analysed the
      chewed food of 176 dentate subjects with a single and a multiple sieve method.
      Furthermore, we quantified the influence of age, gender, and dental status on the
      masticatory performance in order to compare the sensitivity of both methods. We
      observed a significant influence of the number of occlusal units on the
      masticatory performance for both methods. The single sieve method is less
      reliable than the multiple sieve method if the sieve diameter is not close enough
      to the median particle size of the chewed food. Therefore, we recommend the
      multiple sieve method.

PMID- 14693211
TI  - Adaptation of salivary Lactobacillus strains to xylitol.
AB  - OBJECTIVE: Acid production from sugars is one of the virulence factors of
      cariogenic bacteria. To eliminate this factor, many authors have suggested using
      sugar substitutes like xylitol, which is not fermented by most oral bacteria. The
      aim of this work was to investigate whether oral strains of lactobacilli unable
      to utilise xylitol could become able to utilise this polyol. DESIGN: Twenty-eight
      oral strains and six ATCC strains of lactobacilli were tested. None was initially
      able to produce acids from xylitol. Media containing only xylitol was used in
      order to see if an adaptation was possible. The acid production from xylitol was
      measured by recording the pH variations of the culture medium. The acids produced
      were identified by HPLC. RESULTS: After a 15-days culture, 10 strains produced
      acids. After a 40-days culture, 11 more strains produced acid. When acid
      production occurred, lactic, formic, acetic, propionic and butyric acids were the
      organic acids formed by all the strains. CONCLUSIONS: Adaptation of oral strains
      of lactobacilli to xylitol can occur in vitro.

PMID- 14693212
TI  - Antidiabetic potential of Barleria lupulina extract in rats.
AB  - The methanol extract of aerial parts of Barleria lupulina orally tested at doses
      of 100, 200 and 300 mg/kg exerted significant antihyperglycemic effect in
      streptozotocin-induced hyperglycemia in rats [correction].

PMID- 14693213
TI  - Two new O-geranyl coumarins from the resinous exudate of Haplopappus multifolius.
AB  - From the resinous exudate of leaves of Haplopappus multifolius two new coumarins
      were isolated and assigned the structures 6-hydroxy-7-(5'-hydroxy-3',7'
      dimethylocta-2',6'-dien)-oxycoumarin (1) and 6-hydroxy-7-(7'-hydroxy-3',7'
      dimethylocta-2',5'-dien)-oxy coumarin (2).

PMID- 14693214
TI  - Antileishmanial activity of aqueous onion extract in vitro.
AB  - Onion has had an important dietary and medicinal role for centuries. In this
      study the antileishmanial effect of aqueous onion extract (AOE) was investigated.
      Five leishmanial strains in the promastigote stage were studied in vitro. Seventy
      two hour inoculation of AOE gave an IC100 and average IC50 values of 1.25 mg/ml
      and 0.376 mg/ml, respectively, against all leishmanial strains tested.

PMID- 14693215
TI  - Free radical scavenging activity of extracts prepared from fresh leaves of
      selected Chinese medicinal plants.
AB  - The free radical scavenging activity of the 80% methanolic extracts from fresh
      leaves of 300 Chinese medical woody plants was assessed with the aid of the
      stable DPPH radical. Among the plants screened, 56 species had strong free
      radical scavenging capacities, with IC50 values lower than 0.5 mg leaves per
      milliliter. Analysis of the medical uses of these plants showed that most of them
      are employed for their effects on hemostasis, as anti-inflammatory, antimicrobial
      or for treatment of dysentery. These uses may be directly linked to the content
      in tannins and flavonoids and consequently to their free radical scavenging
      activities.

PMID- 14693216
TI  - Protective effect of Spirulina fusiformis on chemical-induced genotoxicity in
      mice.
AB  - Spirulina fusiformis given by oral route to mice at doses of 250, 500 and 1000 mg
      kg(-1) significantly inhibit the genotoxicity induced by cisplatin and urethane.
      In addition, a significant reduction in the extent of lipid peroxidation with
      concomitant increase in the liver enzymatic (GPx, GST, SOD, CAT) and non
      enzymatic (reduced glutathione) antioxidants were observed.

PMID- 14693217
TI  - The aromatic and polyphenolic composition of Roman camomile tea.
AB  - The qualitative and quantitative composition of the main aromatic and
      polyphenolic constituents of infusion from Chamaemelum nobile flowers was
      examined. The camomile tea contained a large amount of polyphenolic compounds
      (340 mg/l), the most important being chamaemeloside (155 mg/l). Only traces of
      essential oil were recovered in tea (7 mg/l).

PMID- 14693218
TI  - Antidiarrhoeal activity of Rhus javanica ripen fruit extract in albino mice.
AB  - The antidiarrhoeal effects of the methanolic extract of Rhus javanica ripen
      fruits (MERJ) were investigated by employing four experimental models of
      diarrhoea in Swiss albino mice. MERJ treated mice, showed significant reduction
      in the faecal output and protected them from castor oil-induced diarrhoea. The
      extract also reduced the intestinal fluid secretion induced by MgSO4 and
      gastrointestinal motility after charcoal meal administration in the albino mice.
      No mortality and visible signs of general weakness was observed in the mice
      following the test extract administration up to 2000 mg/kg dose.

PMID- 14693219
TI  - Paeoniflorin: an antihyperlipidemic agent from Paeonia lactiflora.
AB  - Paeoniflorin (1), isolated from the methanol extract of Paeonia lactiflora,
      showed a lowering effect on cholesterol level in the experimentally-induced
      hyperlipidemic rats. Paeoniflorin showed a significantly lowering effect of total
      cholesterol, LDL and triglyceride levels compared with the control group at the
      dose of 200 and 400 mg/kg, p.o. once a day for 4 weeks.

PMID- 14693220
TI  - Tocopherols, fatty acids and sterols in seeds of four Sardinian wild Euphorbia
      species.
AB  - Sardinian wild Euphorbia pithyusa, E. semiperfoliata, E. dendroides and E.
      characias seed oils were analyzed for their fatty acids, unsaponifiable and
      tocopherol content. Total tocopherol content showed a wide variability, ranging
      from 939 mg/kg in E. semiperfoliata seeds to its absence in E. characias. The
      results on tocopherol content were statistically correlated with both 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radical scavenging test and the beta-carotene
      bleaching antioxidant test. All seeds were rich in linolenic acid, while no
      uncommon fatty acids were detected.

PMID- 14693221
TI  - Insecticidal activity of callus culture of Tagetes erecta.
AB  - The callus tissue of Tagetes erecta maintained on revised Murashige and Skoog's
      medium (RT) as static cultures showed the presence of insecticidal pyrethrins.
      The percentage of pyrethrins further increased by feeding the tissue with various
      concentrations of ascorbic acid. The maximum pyrethrin content (1.68%) was
      observed in 6 weeks old tissue grown on RT medium supplemented singly with 1000
      mg/l of exogenous ascorbic acid. When pyrethrin mixture was screened against
      Tribolium spp. immediate 'knock down' effect was observed.

PMID- 14693222
TI  - Antimicrobial activity of some medicinal plants from Ghana.
AB  - The results of a preliminary antimicrobial screening of the methanol extracts of
      Aframomum melegueta, Piper guineense, Xylopia aethiopica, Zingiber officinale,
      medicinal plants of Ghana, are reported.

PMID- 14693224
TI  - Inhibition of Clotrimazole-resistant Candida albicans by plants used in Iranian
      folkloric medicine.
AB  - In vitro anticandidal activity of methanol extracts of 42 plant species of 29
      families used in Iranian folkloric medicine were evaluated at 20 mg/ml
      concentration against Clotrimazole-resistant Candida albicans. Nineteen plant
      species in 16 families showed anticandidal activities. The lowest MIC of 0.62
      mg/ml belonged to Terminalia chebula and Thymus vulgaris.

PMID- 14693223
TI  - Antimicrobial screening of plants used for traditional medicine in the state of
      Perak, Peninsular Malaysia.
AB  - Seventy-two extracts (methanol) obtained from the leaves, barks, and roots of 50
      plant species used in the traditional medicine of Perak, Peninsular Malaysia,
      have been screened for antibacterial and antifungal activities. Peristrophe
      tinctoria, Polyalthia lateriflora, Knema malayana, Solanum torvum, Celosia
      argentea, Eclipta prostrata, Ancistrocladus tectorius, Dillenia suffruticosa,
      Piper stylosum and Rafflesia hasseltii displayed the broadest spectrum of
      activity.

PMID- 14693225
TI  - Comparative studies on biological activities of Prunus padus and P. spinosa.
AB  - Comparative studies on the antibacterial and free radical scavenging activities
      of the n-hexane, dichloromethane and methanol extracts of the seeds of Prunus
      padus and P. spinosa have been carried out. General toxicity of these extracts
      has also been determined.

PMID- 14693226
TI  - Irritant potential of some constituents from oleo-gum-resin of Commiphora myrrha.
AB  - The irritant potentials of essential oil and seven sesquiterpenoids compounds
      newly isolated from the oleo-gum-resin of Commiphora myrrha were investigated by
      open mouse ear assay. The essential oil, curzerenone, furanodiene-6-one and
      furanoeudesma-1,3-diene showed potent and persistent irritant effects while
      others possess least irritant potentials.

PMID- 14693227
TI  - Antibacterial and antifungal activities of Trewia polycarpa roots.
AB  - The total alcoholic extract, its chloroform soluble and aqueous fractions of the
      roots of the plant Trewia polycarpa exhibited varying degrees of antibacterial
      and antifungal activities when tested with six bacterial and four fungal strains.

PMID- 14693228
TI  - Bioactive flavonoids from Kaempferia parviflora.
AB  - Nine flavonoids (1-9) have been isolated from Kaempferia parviflora. Among these,
      5,7,4'-trimethoxyflavone (8) and 5,7,3',4'-tetramethoxyflavone (9) exhibited
      antiplasmodial activity against Plasmodium falciparum, with IC50 values of 3.70
      and 4.06 microg/ml, respectively. 3,5,7,4'-Tetramethoxyflavone (7) and compound 8
      possessed antifungal activity against Candida albicans with respective IC50
      values of 39.71 and 17.63 microg/ml, and also showed mild antimycobacterial
      activity with the minimum inhibitory concentrations (MIC) of 200 and 50
      microg/ml, respectively. However, none of the isolated compounds demonstrated
      cytotoxicity against KB, BC and NCI-H187 cell lines.

PMID- 14693229
TI  - Antimicrobial activity of Rubus chamaemorus leaves.
AB  - The antibacterial activity of Rubus chamaemorus leaf butanolic fraction of the
      methanol extract and ellagic acid was evaluated against some Gram-positive and
      Gram-negative bacteria. Antimycotic activity was assayed against Candida
      albicans. MICs and MBCs were determined by broth dilution test and by disc
      diffusion method.

PMID- 14693230
TI  - New prenylated isoflavanones and other constituents of Lespedeza bicolor.
AB  - Two prenylated isoflavanones (1) and (2) were isolated from the stem bark of
      Lespedeza bicolor along with the known compounds ethyl caffeate, caffeic acid,
      protocatechuic acid, betulinic acid, betulin, beta-sitosterol and from the stem
      heartwood daidzein and isoliquiritigenin.

PMID- 14693231
TI  - Dihydrochalcones and coumarins of Esenbeckia grandiflora subsp. brevipetiolata.
AB  - Six furoquinolines and five coumarins have been isolated from the roots of
      Esenbeckia grandiflora subsp. brevipetiolata. The leaves yielded two
      dihydrochalcones and two flavonol rhamnosides. One of the coumarins (5-senecioyl
      xanthotoxin) and the dihydrochalcones are novel compounds and their structures
      were elucidated by spectroscopic methods. The comparison with the
      dihydrochalcones previously isolated from another subspecies, E. grandiflora
      subsp. grandiflora is also provided.

PMID- 14693233
TI  - Prognostic and predictive factors in oral squamous cell cancer: important tools
      for planning individual therapy?
AB  - An escalation in the incidence of oral cancer and its attributable mortality has
      been observed in recent decades in Europe; oral cancer is expected to become a
      public health problem in the foreseeable future. However, survival rates have
      remained at a disappointingly stable level despite significant development in the
      multimodality treatment of the disease. Additionally, due to the limited
      prognostic value of conventional prognostic factors and the uniformity of
      treatment strategies, several patients are still over- or under-treated with
      significant personal and socio-economical impact. Here we review some promising
      prognostic and predictive markers that can help the clinician to improve
      prognostic accuracy and define the most appropriate management for the individual
      patient with oral cancer.

PMID- 14693234
TI  - Immune activation and chronic inflammation as the cause of malignancy in oral
      lichen planus: is there any evidence ?
AB  - The association of chronic inflammation with a variety of epithelial malignancies
      has been recognised for centuries. Well established examples include, among many
      others, oesophageal adenocarcinoma associated with chronic oesophagitis and bowel
      cancer associated with chronic inflammatory bowel diseases. By now no data, other
      than clinical observation, have been available in understanding the pathogenesis
      of these inflammation-related tumours. However, recent molecular studies on the
      relationship between solid malignancies and the surrounding stroma have given new
      insights. There is now enough evidence to accept that the chronic inflammatory
      process per se is able to provide a cytokine-based microenvironment which is able
      to influence cell survival, growth, proliferation, differentiation and movement,
      hence contributing to cancer initiation, progression, invasion and metastasis.
      Here it is discussed whether also oral lichen planus (OLP), being a chronic
      inflammatory autoimmune disease which has been clinically associated with
      development of oral squamous cell carcinoma, might be categorised among these
      disorders. With this aim, we critically reviewed and detailed the presence, in
      OLP subepithelial infiltrate, of inflammatory cells and cytokine networks that
      might act to promote squamous tumorigenesis.

PMID- 14693235
TI  - Cancer and oral lichen planus in a Swedish population.
AB  - Oral lichen planus (OLP) is generally regarded as a premalignant condition. The
      objective of the present study was to assess the number of oral malignant tumours
      in a retrospective analysis of 1028 patients (mean age=55 years; range=18-86;
      female, n=667; men, n=351) who between 1978 to end of 1993 were diagnosed with
      OLP at the Faculty of Odontology, Goteborg University, Sweden. Patients with
      malignant tumours were identified through the Swedish Cancer Registry at the
      National Board of Health and Welfare, which annually reports the incidence of
      malignant neoplasms in the Swedish population. The incidence of oral squamous
      cancer (OSCC), other malignant tumours and survival in the study group was
      compared to the Swedish population. The total time with OLP in the study group
      amounted to 7009 person years, with a mean follow up of 6.8 years (SD=4.9). The
      observed incidence of OSCC was higher than the expected incidence in the study
      group. The difference was statistically significant (P<0.001). No statistically
      significant difference was found for any other malignant tumours than OSCC. Also,
      no statistically significant difference could be identified in survival between
      study group and the population. The results from the present study gives further
      support to the concept of a small but increased risk for development of squamous
      cell carcinoma in patients with OLP.

PMID- 14693236
TI  - Identification and overexpression of human neutrophil alpha-defensins (human
      neutrophil peptides 1, 2 and 3) in squamous cell carcinomas of the human tongue.
AB  - To date, little attention has been paid to the possible role of alpha-defensins
      (human neutrophil peptides 1-3), HNP-1, HNP-2 and HNP-3 in innate host defence
      against tumour invasion. In the current study, using a single-dimensional high
      pressure liquid chromatography (HPLC) method for peptide separation, followed by
      mass spectrometry and amino acid sequencing for identification and quantitation,
      we report the overexpression of HNP-1, HNP-2 and HNP-3 in squamous cell
      carcinomas of the human tongue compared with autogenous non-tumour tissue. Using
      a specific antibody we show that the defensins are abundant in neutrophils
      infiltrating human oral squamous cell carcinoma tissue. In the context of their
      previously reported oncolytic activity, our results may imply a role for alpha
      defensins in host defence against oral squamous cell carcinoma.

PMID- 14693237
TI  - Concurrent hypermethylation of multiple regulatory genes in chewing tobacco
      associated oral squamous cell carcinomas and adjacent normal tissues.
AB  - The methylation pattern in the promoter region of p16, DAPK, MGMT and GSTP1 genes
      was investigated in oral cancer tissues and tumor associated adjacent tissues,
      using methylation specific PCR assay. The samples constituted 60 primary oral
      tumors and corresponding adjacent clinically and histopathologically normal
      mucosa, and buccal epithelial scrapings from 20 normal healthy individuals
      without any tobacco habits. The incidence of hypermethylation in oral tumor and
      adjacent mucosa for p16 gene was 66.7 and 50%, for DAPK was 68.3 and 60%, and
      MGMT gene was 51.7 and 26.7%, respectively. The overall hypermethylation in the
      three genes in the primary tumor was 86.7%, and corresponding adjacent normal
      mucosa tissues 76.7%. Hypermethylation was not observed in the promoter region of
      GSTP1 gene in either the primary tumors or the corresponding adjacent normal
      mucosa. Absence of aberrant methylation in the four genes was noted in buccal
      scrapings from normal healthy individuals with no tobacco habits. Thus, a high
      frequency of promoter region hypermethylation was observed in p16, DAPK and MGMT
      genes in oral cancer tissues as well as in corresponding adjacent normal mucosa.
      Our results indicate that epigenetic alteration of these genes is a frequent
      event in oral cancer, and is an early event observed in normal oral mucosa of the
      patients, indicating the critical importance of the epigenetic alteration in
      chewing tobacco associated oral carcinogenesis.

PMID- 14693238
TI  - Investigation of CXCR4 in squamous cell carcinoma of the tongue.
AB  - Cancer metastasis is not a random process and different cancer types have
      favorite metastatic sites. Recent studies on metastasis have focused on
      chemoattraction, particularly on the role of chemokines. Therefore, in this study
      we investigated whether CXCR4 (receptor for stromal cell-derived factor-1) is
      expressed in squamous cell carcinoma of the tongue. For this purpose,
      immunohistochemical staining was performed on 26 sections obtained from 23
      patients (15 patients having tongue tumor without lymph node metastasis and eight
      patients having lymph node metastasis). All tumor cells expressed CXCR4, whereas
      normal mucosa of the tongue had no or faint expression CXCR4. Metastatic tumor
      cells in lymph nodes had stronger expression than primary tongue tumor cells. Our
      data raises the possibility that CXCR4 could be involved in lymph node metastasis
      of oral squamous cell carcinoma.

PMID- 14693239
TI  - Clinical risk factors of oral leukoplakia in a representative sample of the US
      population.
AB  - Studies on the risk factors of oral leukoplakia (OL) are relatively scarce. The
      objectives of this paper are to assess the clinical risk factors of OL in a
      representative sample of the US population. Data from the oral mucosal tissue
      assessment and some other covariates of 15,811 participants in the US National
      Health and Nutrition Examination Survey (NHANES III) were included. The clinical
      definition of OL was applied according to the WHO criteria. Tobacco smoking was
      found as the strongest independent risk factor. The OR were 3.00 (0.77-11.8) for
      < or =10 cigarettes/day up to 6.01 (2.4-15.0) for >20 cigarettes/day. Diabetes,
      age and socio-economic status were found as independent predictors of OL. Alcohol
      consumption, race/ethnicity, years of education and BMI showed no independent
      association with OL. Females with a history of estrogen use were less likely to
      have OL with an OR of 0.34 (0.11-1.07). In conclusion, the role of diabetes and
      estrogen in the pathogenesis of OL should be further investigated.

PMID- 14693240
TI  - Prognostic significance of p34cdc2 expression in tongue squamous cell carcinoma.
AB  - We evaluated the prognostic significance of p34cdc2 expression in 50 tongue
      squamous cell carcinomas (SCC) using immunohistochemical methods. The p34cdc2
      protein was expressed in 33 cases of 50 tumor tissues (66.0%), compared with 15
      cases of 42 controlled epithelia (35.7%). The expression of p34cdc2 was
      significantly correlated with the histological grade of tongue carcinoma
      (P<0.01). In addition, on evaluation of prognosis of tumor, the p34cdc2 protein
      was overexpressed in recurrent tumors or in those with lymph node metastasis.
      Statistics showed a significant reduction in the 5-year accumulative survival
      rate of p34cdc2 positive cases compared with p34cdc2 negative cases (P<0.01).
      Namely, the p34cdc2 positive patients had worse prognosis. The results suggested
      that the expression of p34cdc2 suited to the histological grade might reflect the
      malignant degree of tongue carcinoma biologically. Therefore, the evaluation of
      p34cdc2 expression was of benefit in elucidating the nature of tumor malignancy
      and the prognostic prediction of tongue SCC.

PMID- 14693241
TI  - The relationship between mucosal cyclooxygenase-2 (COX-2) expression and
      experimental radiation-induced mucositis.
AB  - Although cycloooxygenase-2 (COX-2) is upregulated by factors associated with oral
      mucositis, its role in the pathogenesis of mucositis has not been studied. We
      investigated the kinetics of mucosal COX-2 expression following radiation
      exposure, and assessed its relationship to the development of oral mucositis in
      an established animal model using immunohistochemical endpoints. While little or
      no COX-2 expression was observed in unirradiated mucosa or in tissue taken 2 days
      after radiation, COX-2 expression was dramatic on days 10 and 16, especially in
      submucosal fibroblasts and endothelium. The kinetics of COX-2 expression
      paralleled mucositis severity. A burst of angiogenic activity was seen on day 21
      following peak COX-2 expression. The kinetics of COX-2 expression relative to
      mucositis progression suggests that COX-2 is not a primary driver of radiation
      injury, but instead plays an amplifying role.

PMID- 14693242
TI  - The CAG repeat polymorphism in the androgen receptor gene (AR) and its
      relationship to head and neck cancer.
AB  - Sex hormones may play an important role in the tumorigenic process of the head
      and neck. The aim of our work was to investigate whether the androgen receptor
      (AR) CAG repeat polymorphism is associated with an increased relative risk for
      head and neck cancer. Genomic DNA from 103 male patients with head and neck
      carcinomas and 100 male controls were analyzed for the AR CAG polymorphism by PCR
      amplification and direct sequencing or denaturing polyacrilamide gel
      electrophoresis. Logistic regression analysis showed a significant association
      between CAG repeat length and risk of head and neck cancer in individuals with
      more than 20 CAG repeats [OR=2.54 (95% CI, 1.3-4.8)]. For the group of
      individuals with oral and laryngeal cancer the estimated relative risk was
      increased to 2.79 (95% CI, 1.2-6.3) and 3.06 (95% CI, 1.0-9.6), respectively, in
      men with CAG repeat length >20. These results suggest, for the first time, that
      shorter AR CAG repeat alleles have a protective effect for head and neck cancer
      development.

PMID- 14693243
TI  - Salvage surgery as the primary treatment for recurrent oral squamous cell
      carcinoma.
AB  - The choice of salvage modalities of recurrent squamous cell carcinoma (SCC) of
      the oral cavity remains controversial. We investigated the feasibility of the
      surgical salvage treatment as a primary option. From 1989 to 1999, curative
      intended surgery was performed on 191 patients with SCC of the oral cavity at
      National Cheng Kung University Hospital in Taiwan. These patients were divided
      into fresh group and salvage group. Survival and complication rates were analyzed
      for both groups. Patients with early and late recurrent stage had 60 and 38% 5
      year absolute survival after salvage surgery. The overall complication rate was
      higher in the salvage group (60.7 vs 30.4%, P<0.0001), but the major complication
      rate was not significantly different between these groups (P=0.121). Surgery
      achieves an acceptable survival in recurrent oral SCC without increasing the
      major complication rate. Thus surgery is concluded to be a reliable and feasible
      treatment of choice.

PMID- 14693244
TI  - Diagnostic significance of FDG-PET and argyrophilic nucleolar organizer regions
      (AgNORs) in oral squamous cell carcinoma.
AB  - Neoadjuvant chemoradiotherapy has played an important role in preserving organs
      and functions in patients with oral squamous cell carcinoma (SCC). To determine
      whether further operation after chemoradiotherapy is necessary, accurate
      evaluation of residual tumour cells after treatment is essential. We investigated
      the usefulness of regional fluorodeoxyglucose (FDG) uptake in combination with
      histochemical expression of AgNORs obtained from pretreatment biopsy specimens to
      assess residual tumours after intraarterial chemoradiotherapy. Standardized
      uptake value (SUV: pretreatment, pre-SUV; post-treatment, post-SUV) was
      calculated to determine the changes of FDG uptake in the tumour before and after
      chemoradiotherapy. Four out of 20 patients with oral SCCs showed residual tumour
      cells after treatment. Tumours with higher post-SUVs (> or =4.0) and higher
      AgNORs scores (> or =5.0) had significantly higher incidences of residual viable
      tumour cells after chemoradiotherapy (P=0.001). The results suggest that the
      combination of FDG-PET with AgNORs score is an excellent index for determining
      the optimal management of each patient following neoadjuvant chemoradiotherapy.

PMID- 14693245
TI  - Okadaic acid stimulates expression of Fas receptor and Fas ligand by activation
      of nuclear factor kappa-B in human oral squamous carcinoma cells.
AB  - In the present study, we used western blot and RT-PCR analysis to examine the
      expression of proteins and mRNAs of Fas receptor and Fas ligand in human oral
      squamous carcinoma SCC-25 cells treated with okadaic acid. Treatment with okadaic
      acid enhanced the expression of proteins and mRNAs of both Fas receptor and Fas
      ligand in SCC-25 cells. The amount of IkappaB-alpha in whole cell lysates
      decreased, while the level of NF-kappaB in nucleus increased, in the okadaic acid
      treated cells. Okadaic acid-treatment also alters the cellular localization of NF
      kappaB, from cytoplasm to nuclei. To investigate the activation of NF-kappaB in
      okadaic acid-treated SCC-25 cells, we performed electrophoretic mobility gel
      shift assay using nuclear extracts and the consensus oligonucleotide for NF
      kappaB DNA binding site. The binding of nuclear proteins to the oligonucleotide
      of NF-kappaB increased when the cells had been treated with 20 nM okadaic acid
      for 4 h. We transfected the cells with pFLF1, which has the promoter region of
      Fas receptor gene containing NF-kappaB binding site. A luciferase reporter gene
      assay demonstrated that the activity in the cells transfected with pFLF1 and
      treated with 20 nM okadaic acid increased in a time-dependent manner and that the
      activity was more than three-fold over that in the control cells. Our results
      suggest that NF-kappaB activated at early stages in the okadaic acid-treated SCC
      25 cells stimulated the promoter activity of Fas receptor in the cells leading to
      the apoptotic death of these cells.

PMID- 14693246
TI  - Risk factors for oral and pharyngeal cancer in young adults.
AB  - Mortality from oral cancer has been rising in the young in several areas of the
      world until the early 1990s. We analysed data from two case-control studies from
      Italy and Switzerland including 137 cases of oral and pharyngeal cancer below age
      46 and 298 hospital controls. The multivariate odds ratios (OR) were 20.7 for
      heavy smokers and 4.9 for heavy drinkers. The combination of high tobacco and
      alcohol consumption led to an OR of over 48. Body mass index (OR=0.28, for the
      highest tertile), high consumption of coffee (OR=0.25), fresh vegetables
      (OR=0.39), fruit (OR=0.73) and beta-carotene (OR=0.48) were inversely related to
      risk. Tobacco accounted for 77% of all cancer cases in this population, alcohol
      for 52%, low vegetable consumption for 52%, and the combination of the three
      factors for 85%.

PMID- 14693247
TI  - Endothelial cells increase the radiosensitivity of oropharyngeal squamous
      carcinoma cells in collagen gel.
AB  - We assessed the radiosensitivity of human HSCO oropharyngeal squamous carcinoma
      cells in the presence of paracrine factors produced by human HECV umbilical vein
      endothelial cells. To this end the cells were embedded in separate collagen gels
      at the density of 1 x 10(6) cells/ml each, and the two gels were placed in a well
      of a six-well plate, sharing the same medium but without physical contact (two
      gel model). The medium was not changed during the observation period to ensure
      the accumulation of soluble factors. On day 2 of culture the gels were irradiated
      with 0, 0.5, 1, 2 and 8 Gray (Gy) and on day 7 of culture they were disaggregated
      and cell survival evaluated by the MTT assay. Results were compared with proper
      untreated and irradiated control groups. Under these experimental conditions it
      was found that: (1) HSCO and HECV cells influenced reciprocally their behaviour
      in the two-gel model, in terms that cell survival was enhanced and inhibited,
      respectively; (2) as expected, HSCO cells were more radioresistant in collagen
      gel than in monolayer; (3) on the average the survival of HECV cells was enhanced
      at low radiation doses, irrespective of whether they were cultured alone or with
      HSCO cells in the two-gel model and (4) HSCO cells displayed a high
      radioresistance when irradiated alone at doses from 0.5 to 8 Gy. However, when co
      cultured with HECV cells in the two-gel model, they become highly radiosensitive
      already at the dose of 2 Gy, while none of them survived at the dose of 8 Gy.
      This radiosensitizing effect was specifically induced by paracrine factors
      circulating in the medium, supporting the notion that stromal endothelial cells
      may be essential components of a metabolic circuitry supplying solid tumors with
      radiosensitizing factors.

PMID- 14693248
TI  - Predictive factors and distribution of lymph node metastasis in lip cancer
      patients and their implications on the treatment of the neck.
AB  - The frequency of neck metastasis in lip cancer patients is low, however if
      present, it decreases survival rates, which reinforce the neck treatment as an
      important step in the management of these patients. This study evaluates the
      predictive factors, the distribution of lymph node metastasis and their
      implications on the neck treatment. A retrospective analysis of lip cancer
      patients treated in our institution from 1969 to 1999 was performed. A total of
      617 patients were analysed. One hundred and seven patients (17.3%) were submitted
      to a neck dissection. T3/T4 tumours and commissure involvement were significantly
      associated with the risk of neck metastasis (P<0.001 and P=0.004, respectively).
      No cases had levels IV and V involved with node metastasis, either clinically or
      pathologically. The results suggest that supraomohyoid neck dissection could be
      the option for the elective treatment in T3/T4 tumours and those with commissure
      involvement, and the therapeutic option for patients with clinically positive
      necks.

PMID- 14693249
TI  - Cilengitide (EMD 121974) arrests the growth of a heavily pretreated highly
      vascularised head and neck tumour.
AB  - The suppression and eradication of malignant tumours by targeting the endothelial
      cells of the tumour is one of the rapidly evolving new approaches to cancer
      therapy. Head and neck tumours, because of their high levels of vascularization,
      present themselves as ideal candidates for such antiangiogenic strategies. We
      report a heavily pretreated patient with a tumour 15 cm in diameter representing
      fourth relapse of squamous cell carcinoma, which had its origin in the upper left
      jaw. The patient was treated with the antiangiogenetic, cyclic peptide, EMD
      121974 [cilengitide] (600 mg/m2 over 60 minutes i.v.) on day 1 and 4 in
      combination with gemcitabine (1000 mg/m2 over 30 minutes) administered days 1 and
      8 every 3 weeks for five months, and a partial remission was achieved. This
      resulted in a clinical improvement in the ability of the patient to eat and
      smell. The patient remained stable for 12 months on cilengitide mainenance
      therapy, with no tendency towards spontaneous bleeding. This clinical case
      demonstrates the clinical efficacy of the antiangiogenetic agent cilengitide, in
      combination with gemcitabine, in inhibiting rapid growth of highly vascularized
      tumour and highlights the potential of this new therapeutic agent

PMID- 14693250
TI  - DNA stability of forensic STR markers in FTA-extracted buccal DNA of betel-quid
      chewers.

PMID- 14693252
TI  - On "Gradualism" and the building of the harm reduction-abstinence continuum.
AB  - This paper makes the case that a perspective called "Gradualism" could serve as a
      foundation for building a therapeutic continuum between the harm reduction and
      abstinence-oriented treatment worlds. In contrast to other integrationist writers
      (Denning, 2001; Marlatt, Blume, & Parks, 2001), this paper argues for the
      incorporation of abstinence into harm reduction approaches. The goal is to build
      on the strengths of both perspectives while reducing their weaknesses, and
      examples of each are provided. Lastly, with the frequent occurrence of relapse
      among addicted patients, building a continuum could also serve to provide a
      therapeutic "safety net" for those in need.

PMID- 14693253
TI  - Harm reduction psychotherapy: extending the reach of traditional substance use
      treatment.
AB  - Harm reduction is a paradigm-shifting idea that has the potential to
      significantly improve the treatment of problem substance users. The essence of
      harm reduction is the recognition that treatment must start from the client's
      needs and personal goals and that all change that reduces the harms associated
      with substance use can be regarded as valuable. The paper presents harm
      reduction's rationale, principles, treatment implications, and application to
      psychotherapy. The author describes his model of Integrative Harm Reduction
      Psychotherapy, an approach that integrates a strategic skills-building focus with
      an exploration of the multiple meanings of substance use and the importance of
      the therapeutic alliance.

PMID- 14693254
TI  - SACHR: an example of an integrated, harm reduction drug treatment program.
AB  - In this article, we report on our work at St. Ann's Corner of Harm Reduction, a
      multi-service agency committed to implementing effective public health strategies
      in disenfranchised communities from a harm reduction perspective. Based on our
      experiences, we hope to contribute to the ongoing dialogue about the definition
      of harm reduction, while proposing to integrate harm reduction and abstinence
      oriented treatment modalities into a model of comprehensive drug prevention and
      care. The five components of our harm reduction service provision are discussed,
      and a vignette is provided. We conclude with a plea for close collaborations
      between innovative researchers and harm reduction agencies, and a call for the
      full integration of harm reduction approaches into the substance abuse field at
      large.

PMID- 14693255
TI  - Patterns of substance abuse among treatment-seeking pathological gamblers.
AB  - Substance abuse patterns were reviewed for a group of patients admitted to the
      Gambling Treatment Program at the Brecksville Veterans Administration Medical
      Center. A retrospective chart review of 113 consecutively admitted patients
      between September 2000 and September 2001 found that 66.4% of pathological
      gamblers had a lifetime history of substance abuse or dependence at some point in
      their lives. A history of substance abuse or dependence was less common among
      gamblers aged 60 and above. In the year prior to admission, 58.1% of those with a
      history of substance abuse or dependence were actively using substances. Alcohol
      was the most commonly used substance, followed by marijuana and cocaine. In most
      gamblers with comorbid disorders, the onset of substance dependence preceded the
      onset of problem gambling. Pathological gamblers engaged in multiple impulsive
      and dysfunctional behaviors including suicide attempts, compulsive shopping and
      spending, and compulsive sexual behavior, and the presence of comorbid substance
      abuse disorders may influence the degree to which pathological gamblers engage in
      these additional problematic behaviors. These factors have important implications
      for treatment and prevention of relapse, as well as for theories of addictions.

PMID- 14693256
TI  - Performance measures for outpatient substance abuse services: group versus
      individual counseling.
AB  - Most substance abuse treatment programs employ various models of group therapy.
      Empirical evidence, however, of the benefits of group vs. individual treatment is
      scarce. This study examined the impact of type of treatment, defined as
      individual or group counseling, on treatment performance, as measured by
      treatment completion and goal achievement. Data on clients treated in publicly
      funded substance abuse outpatient treatment programs were drawn from the
      Massachusetts Substance Abuse Information System. A larger proportion of group to
      individual therapy was strongly and positively associated with increased
      likelihood for improved measures of treatment performance. State data systems can
      provide useful insights into the development and application of performance
      measurement.

PMID- 14693257
TI  - Distance traveled to outpatient drug treatment and client retention.
AB  - This study examined the association between approximate distance traveled to
      treatment, and treatment completion and length of stay, for 1,735 clients
      attending outpatient treatment in an urban area. Clients who traveled less than 1
      mile were 50% more likely to complete treatment than clients who traveled more
      than 1 mile, after holding constant demographic variables and type of drug
      problem. Similarly, clients who traveled more than 4 miles were significantly
      more likely to have a shorter length of stay than clients who traveled less than
      1 mile. These findings have important implications for the geographic placement
      of new treatment facilities, as well as the provision of transportation services
      to maximize treatment retention.

PMID- 14693258
TI  - Exploratory findings from the Reasons for Drinking Questionnaire.
AB  - Marlatt and Gordon's (1985) relapse prevention therapy has received widespread
      interest and application. The categorization of relapse precipitants was one of
      the original central features of this model. In more recent iterations of this
      therapy, increasing emphasis has been placed on coping strategies. In the present
      article, exploratory findings from a prospective naturalistic alcohol treatment
      study employing the Reasons for Drinking Questionnaire are reported. A relapse
      precipitants scoring algorithm is presented allowing relapses to be categorized
      as either negative affect relapses, social pressure relapses, or craving/cued
      relapses. Exploratory findings suggest that social pressure relapses are more
      likely to repeat, and that negative affect and craving/cued relapses are more
      severe. Perhaps most interestingly, craving/cued relapses appear to subside
      during the first 6 months following treatment initiation, but subsequent risk for
      this type of relapse returns if the client has relapsed. However, these findings
      are still early in a continuing exploration of these issues in relapse
      prevention.

PMID- 14693259
TI  - Clinical practices in the pharmacological treatment of comorbid psychopathology
      in adolescents with alcohol use disorders.
AB  - This study examined the use of psychiatric medications in 277 adolescents in
      treatment for alcohol use disorders. Subjects were recruited from addictions
      treatment sites, psychiatric programs, and juvenile justice settings.
      Characteristics studied included the use of and indications for specific
      medications, changes in clinical practices from 1991 through 2000, and
      continuation of psychopharmacological treatment over a 1-year followup period.
      Among adolescents taking psychiatric medications at baseline (n = 51), indicated
      DSM-IV mental disorders were typically present, use of antidepressants was most
      common (n = 41), benzodiazepine prescription was rare, and about one third
      reported continuing pharmacological treatment at one-year followup. In those with
      comorbid major depressive disorder and alcohol use disorders (n = 110),
      antidepressant medication use increased significantly from 18% to 55% over the
      decade studied. The treatment setting did not significantly influence
      antidepressant prescribing practices. The common and increasing use of
      psychiatric medications in this population emphasizes the urgent need for
      empirically based clinical guidelines.

PMID- 14693260
TI  - Publication of negative research findings: pros and cons.

PMID- 14693261
TI  - Autoshaping of ethanol drinking in rats: effects of ethanol concentration and
      trial spacing.
AB  - In two studies, we evaluated the effects of ethanol concentration and trial
      spacing on Pavlovian autoshaping of ethanol drinking in rats. In these studies,
      the brief insertion of an ethanol sipper conditioned stimulus (CS) was followed
      by the response-independent presentation of food unconditioned stimulus (US),
      inducing sipper CS-directed drinking conditioned responses (CRs) in all rats. In
      Experiment 1, the ethanol concentration in the sipper CS [0%-16% volume/volume
      (vol./vol.), in increments of 1%] was systematically increased within subjects
      across autoshaping sessions. Groups of rats received sipper CS-food US pairings
      (Paired/Ethanol), a CS-US random procedure (Random/Ethanol), or water sipper CS
      paired with food US (Paired/Water). In Experiment 2, saccharin-fading procedures
      were used to initiate, in the Ethanol group, drinking of 6% (vol./vol.) ethanol
      in 0.1% saccharin or, in the Water group, drinking of tap water in 0.1%
      saccharin. After elimination of saccharin, and across days, the duration of
      access to the sipper CS during each autoshaping trial was increased (5, 10, 12.5,
      15, 17.5, and 20 s), and subsequently, across days, the duration of the mean
      intertrial interval (ITI) was increased (60, 90, 120, and 150 s). In Experiment
      1, Paired/Ethanol and Random/Ethanol groups showed higher intake of ethanol, in
      terms of grams per kilogram of body weight, at higher ethanol concentrations,
      with more ethanol intake recorded in the Paired/Ethanol group. In Experiment 2,
      the Ethanol group drank more than was consumed by the Water group, and, for both
      groups, fluid intake increased with longer ITIs. Results support the suggestion
      that autoshaping contributes to sipper CS-directed ethanol drinking.

PMID- 14693262
TI  - Immune response modulation in acutely ethanol-intoxicated, acutely diabetic male
      and female rats.
AB  - We examined how acute diabetes mellitus and acute ethanol intoxication modulate
      factors that mediate immune responses as a basis for explaining the increased
      susceptibility to infection in these two conditions. Our working hypothesis is
      that ethanol intoxication in diabetes compromises host defense mechanisms to a
      greater extent than observed in each condition alone. Male and female rats were
      made diabetic with streptozotocin (65 mg/kg, i.p.). Forty-eight hours after
      administration of streptozotocin, rats either received no treatment (control
      group) or were treated with (1) ethanol (bolus injection of 1.75 g/kg, followed
      by a 3-h infusion at the rate of 300 mg/kg/h), (2) lipopolysaccharide [(LPS); 0.9
      mg/kg], or (3) a combination of LPS+ethanol. At the end of 3 h, rats were killed,
      and the livers were digested by perfusion with collagenase-containing Hanks'
      balanced salt solution to isolate hepatocytes and Kupffer cells. To measure
      chemokine generation, hepatocytes (2.5x10(5) cells per well) and Kupffer cells
      (1x10(6) cells per well) were cultured for 20 h, and the supernatant was used to
      measure cytokine-induced neutrophil chemoattractant (CINC) and regulated on
      activation, normal T-cell expressed and secreted (RANTES) chemokines.
      Phagocytosis by Kupffer cells was measured by flow cytometry and expressed as
      mean channel fluorescence intensity (MCF). Induction of diabetes as well as
      treatment of nondiabetic rats with LPS, ethanol, or LPS+ethanol caused depression
      of MCF values of Kupffer cells. However, treatment of the diabetic male and
      female rats with LPS and LPS+ethanol increased the MCF values relative to those
      of Kupffer cells obtained from untreated diabetic rats, but administration of
      ethanol to diabetic rats did not have a similar effect. The induction of diabetes
      caused an increase in CINC generation by Kupffer cells obtained from male rats,
      but not from female rats. This diabetes-induced elevation of chemoattractant
      factor was decreased when diabetic animals were treated with LPS, ethanol, or
      LPS+ethanol, and the sex difference was obliterated. Thus, the induction of
      diabetes as well as treatment with LPS, ethanol, or LPS+ethanol in nondiabetic
      rats depressed the phagocytic capability of Kupffer cells, whereas the presence
      of endotoxemia (administration of the endotoxin LPS) or administration of
      LPS+ethanol reversed the diabetic effect, but ethanol intoxication did not. These
      findings seem to indicate a persistence of depression of host defense capacity in
      the ethanol-intoxicated diabetic condition. This is further reinforced by the
      depression of the diabetes-induced enhancement of chemotaxis when the diabetic
      rats became intoxicated.

PMID- 14693263
TI  - Alpha 7 nicotinic acetylcholine receptor-mediated protection against ethanol
      induced neurotoxicity.
AB  - The alpha(7)-selective nicotinic partial agonist 3-[2,4
      dimethoxybenzylidene]anabaseine (DMXB) was examined for its ability to modulate
      ethanol-induced neurotoxicity in primary cultures of rat neurons. Primary
      cultures of hippocampal neurons were established from Long-Evans, embryonic day
      (E)-18 rat fetuses and maintained for 7 days. Ethanol (0-150 mM), DMXB (0-56
      microM), or both were subsequently co-applied to cultures. Ethanol was added two
      additional times to the cultures to compensate for evaporation. After 5 days,
      neuronal viability was assessed with the MTT cell proliferation assay. Results
      demonstrated that ethanol reduces neuronal viability in a concentration-dependent
      fashion and that DMXB protects against this ethanol-induced neurotoxicity, also
      in a concentration-dependent fashion. These results support the suggestion that
      nicotinic partial agonists may be useful in treating binge drinking-induced
      neurotoxicity and may provide clues as to why heavy drinkers are usually smokers.

PMID- 14693264
TI  - Central neuropeptide Y alters ethanol-induced sedation, but not ethanol intake,
      in C57BL/6 mice.
AB  - Recent evidence indicates that neuropeptide Y modulates neurobiologic responses
      to ethanol and ethanol consumption. Resistance to the sedative effects of
      ethanol, voluntary ethanol consumption, or both was found to be inversely related
      to neuropeptide Y levels in genetically manipulated rat and mouse models. More
      recently, intracerebroventricular infusion of neuropeptide Y reduced ethanol
      drinking in rats selectively bred for high ethanol preference, but not in low
      ethanol-preferring or in outbred Wistar rats. In the current study, we determined
      whether intracerebroventricular infusion of neuropeptide Y would reduce voluntary
      ethanol consumption in high-ethanol-preferring, C57BL/6 mice. We also studied
      ethanol-induced sedation after intracerebroventricular infusion of neuropeptide
      Y. Pretreatment with doses of neuropeptide Y, ranging from 3.0 to 10.0 microg,
      significantly augmented ethanol-induced sedation without altering locomotor
      activity or plasma ethanol levels. However, neither a 5.0- nor a 10.0-microg dose
      of neuropeptide Y altered 2-h drinking of a 10% [volume/volume (vol./vol.)]
      ethanol solution. Consistent with genetic evidence, the results of current
      pharmacologic studies provide support that neuropeptide Y modulates ethanol
      induced sedation.

PMID- 14693265
TI  - Failure of a schedule-induction procedure to increase ethanol intake in an
      established limited-access self-administration condition.
AB  - Determining mechanisms that can increase ethanol consumption during a single
      drinking bout is central to understanding alcohol abuse. When rodents are used as
      models to study excessive drinking, most often limited and transient increases in
      bout size are found with various manipulations. In a variety of studies,
      investigators have reported that schedule-induced drinking can result in
      excessive consumption of either water or alcohol (ethanol) during a single
      drinking period in food-restricted rats. The question examined in this experiment
      was, Could a schedule-induction paradigm increase bout size in nondeprived rats
      already self-administering ethanol? After the rats were trained to self
      administer a 10% (volume/volume) ethanol solution in a fixed daily drinking
      session, non-response-contingent presentation of a 10% (weight/volume) sucrose
      solution, on a fixed-time, 120-s schedule, was used to determine whether
      additional ethanol consumption could be induced. This was followed by the use of
      a fixed-time, 300-s schedule and then, by using the fixed-time, 120-s schedule,
      with the presentation of a 2% (weight/volume) sucrose solution. None of these
      conditions induced an increase in ethanol self-administration. The results
      indicate that factors that control ethanol bout size in the nondeprived rat are
      such that the standard schedule-induction condition seems to be ineffective if an
      ethanol bout has occurred in the recent past.

PMID- 14693266
TI  - Effects of alcohol hangover on cytokine production in healthy subjects.
AB  - A hangover is the syndrome of physical and mental symptoms that occurs 8 to 16 h
      after alcohol consumption with a zero level of alcohol. The aim of the current
      study was to investigate the effects of the alcohol hangover on cytokine
      production in healthy subjects. The hangover state was defined as 13 h after
      drinking 1.5 g/kg of alcohol (blood alcohol level=0). A venous blood sample was
      taken from 20 healthy adult men before consumption of alcohol and during the
      hangover state. Peripheral blood mononuclear cells were separated and stimulated
      with phytohemagglutinin. An enzyme-linked immunosorbent assay was used to measure
      the production of the following cytokines: interleukin (IL)-1beta, IL-4, IL-6, IL
      10, IL-12, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF
      alpha). We found that the concentrations of IL-10, IL-12, and IFN-gamma were
      significantly increased during the hangover state compared with the
      concentrations in normal conditions. These results support the suggestion that
      the dysregulated cytokine pathway (IL-10, IL-12, and IFN-gamma) is associated
      with the symptoms of hangovers.

PMID- 14693267
TI  - Extramedullary plasmacytoma invading the bladder: case report and review of the
      literature.
AB  - Multiple myeloma is characterized by neoplastic proliferation of a single clone
      of plasma cells engaged in the production of a monoclonal protein. This condition
      affects mainly the bone marrow, but extramedullary manifestations can be seen in
      any organ. Urinary bladder involvement is extremely rare, with only 14 cases
      reported in the literature to our knowledge. Herein, we report a large
      extramedullary bladder plasmacytoma arising in a patient with history of multiple
      myeloma. A 78-year-old woman with history of multiple myeloma, currently in
      remission, presented with a large intravesical tumor. Because the tumor was
      considered to have characteristics of anaplastic neoplasm from transitional cell
      origin with evidence of deep muscular invasion, a radical cystectomy was
      performed. A subsequent microscopic evaluation of the cystectomy specimen
      revealed round cells with an eccentric cartwheel-like nucleus suggestive of
      plasmacytoma. The diagnosis was further confirmed with immunohistochemical
      studies. It is difficult, according to the literature, to distinguish bladder
      plasmacytoma from anaplastic transitional cell tumors. It is important to provide
      the pathologist with an appropriate history and to have a high index of suspicion
      for bladder plasmacytoma in patients with previous diagnosis of multiple myeloma
      and bladder mass.

PMID- 14693268
TI  - Renal cell carcinoma (RCC) and telomerase activity: relationship to stage.
AB  - Limited information is available on the correlation of telomerase activity and
      the clinical and pathological characteristics, in patients with renal cell
      carcinoma (RCC). Telomerase repeat amplification protocol (TRAP) was used to
      measure telomerase activity in frozen RCC specimens from partial/radical
      nephrectomies performed between 1987 and 1991. Presence of tumor tissue was
      verified by a pathologist using hematoxylin and eosin stained sections. RNA was
      measured to ensure the presence of intact protein necessary for telomerase
      expression. Data on demographics, tumor type, and stage at presentation, local
      recurrence, distant metastasis, disease-free survival (DFS), and overall survival
      (OS) was collected, and telomerase activity was correlated with each of these
      variables. Forty-nine of 67 patients (73%) were telomerase positive (+ve). Gender
      and stage were the only variables that appeared to be associated with telomerase
      positivity. Tumors were telomerase +ve in 12/21 females (57 %) vs. 37/46 males
      (80%) (P = 0.07). Tumors were telomerase +ve in 85% of Stage IV, 76% of Stage
      III, and 70% of Stage I/II patients (P = 0.12). Five-year survival was 0% for
      Stage IV, 57% for Stage III, and 77% for Stage I/II patients (P < 0.001), DFS 54%
      for stage III and 84% for Stage I/II patients (P = 0.05). Telomerase activity,
      however, was not related to survival in either univariate or multivariate
      analysis. In patients with telomerase +ve tumors 5-year survival was 55%, and
      with telomerase -ve tumors 58% (P = 0.56). Stage was the only variable associated
      with OS or DFS in clear cell RCC patients. In patients with advanced disease,
      there is a high incidence of telomerase positivity was found, within this limited
      sample, however, no correlation with survival was found.

PMID- 14693269
TI  - Current issues in the management of advanced squamous cell carcinoma of the
      penis.
AB  - Effective treatment of penile carcinoma incorporates three modalities: surgery,
      radiation and chemotherapy. Surgery alone may offer a high cure rate in early
      stages of the disease. In certain patients radiation therapy may be utilized to
      eradicate the tumor and allow organ preservation. For patients with locally
      advanced disease, multi-modality approaches incorporating adjuvant or neoadjuvant
      chemotherapy and radiation therapy need to be studied. This approach may confer a
      survival benefit to a group that would otherwise have a poor prognosis. Finally,
      in the setting of metastatic disease, less toxic and more effective combination
      chemotherapy are sought. Novel targeted therapies that have been successful in
      squamous cell carcinoma at other sites must also be studied in this disease. We
      believe that multi-institutional trials should be designed in order to obtain
      prospective benchmark data from which to make valid comparisons of outcome.

PMID- 14693270
TI  - Multivariate models to predict clinically important outcomes at prostatectomy for
      patients with organ-confined disease and needle biopsy Gleason scores of 6 or
      less.
AB  - The objective of this study was to determine the clinical and biopsy features
      associated with outcomes at radical retropubic prostatectomy (RRP) in patients
      with clinically organ-confined prostate cancers and biopsy Gleason scores (GS) of
      6 or less. We reviewed 274 biopsies with GS 6 or less cancers from patients with
      clinically organ-confined disease between 1995 and 1998 to determine
      statistically significant predictors for the following outcomes at RRP: tumor
      volume, small (<0.5 cc), confined (pT2) tumors with RRP GS of 6 or less
      (potentially "insignificant" tumors), and extraprostatic extension (EPE).
      Clinical and pathologic features evaluated included age, serum prostate specific
      antigen (PSA), clinical stage, percent biopsy cores and surface area positive for
      cancer (tumor extent), perineural invasion, MIB-I proliferation, and DNA ploidy
      by digital image analysis (DIA). Multivariate analyses showed that biopsy tumor
      extent (median percent surface area positive 3.3%; P < 0.001 and median biopsy
      cores positive 28.6%; P = 0.001) and PSA (median 5.5 ng/mL; P = 0.009) predicted
      tumor volume (median 1.4 cc). Biopsy tumor extent (P = 0.002), PSA (P = 0.002),
      and percent S-phase nuclei (P = 0.050) predicted potentially "insignificant"
      tumors at RRP (n = 76, 28%). Percent surface area positive for cancer (P = 0.003)
      predicted EPE (n = 22, 8%). DNA ploidy (n = 211, 79% diploid) and MIB-I
      proliferation (median 1.4%) did not add information to predict these RRP
      outcomes. Biopsy tumor extent and serum PSA were significantly associated with
      tumor volume. Biopsy tumor extent, serum PSA, and percent S-phase nuclei by DIA
      were predictive of potentially insignificant tumors. Patients with clinically
      confined disease, <5% biopsy surface area positive for cancer, <20% biopsy cores
      positive for cancer, and GS 6 or less, had a 48% chance of having a potentially
      insignificant tumor at diagnosis if the serum PSA was <10 ng/mL. Percent surface
      area predicted EPE at RRP. DNA ploidy and MIB-I proliferation by DIA did not
      provide additional information.

PMID- 14693271
TI  - Factors associated with blood loss during radical prostatectomy for localized
      prostate cancer in the prostate-specific antigen (PSA)-era: an overview of the
      Department of Defense (DOD) Center for Prostate Disease Research (CPDR) national
      database.
AB  - Radical Prostatectomy (RP) has been traditionally associated with significant
      operative blood loss and high risk of transfusion. However, over the last few
      years, centers of excellence have reported less bleeding and transfusion. To
      verify and document changes in the epidemiology of bleeding and transfusion of
      men electing RP, we undertook an analysis of such cases in the Department of
      Defense (DoD) Center for Prostate Disease Research (CPDR) Multicenter Research
      Database. Using the Department of Defense Center for Prostate Disease Research
      (CPDR) Multicenter National Research Database, a query of all RPs performed
      between January 1, 1985 and December 31, 2000 was conducted revealing 2918 cases
      with blood-loss data available for analysis from nine hospital sites. These cases
      were analyzed over time (calendar year) and changes in the characteristics of the
      patients, disease severity, and surgical results were compared with estimated
      blood loss (EBL) and transfusion data. Among the 2918 evaluable men, 2399 (82%)
      underwent a retropubic RP, 97% had clinical T1-2 disease, and 77% had a PSA level
      > or =10.0 ng/mL. Overall median operation time was 3.8 h, and EBL was 1000 cc.
      Examining trends over time, there was a dramatic decline in median operative
      time, EBL, and transfusion rate. In multiple linear regression analysis,
      operative time, operative approach, surgery year, lymphadenectomy status, and
      neoadjuvant hormonal therapy were significant predictor of EBL. Blood loss
      difference between retropubic and perineal RP became insignificant in the latter
      years. Radical prostatectomy is being performed more commonly on men with earlier
      stage disease in the PSA-Era. The operation is now performed more rapidly with
      less blood loss and fewer transfusion requirements. In a broad practice
      experience represented here, autologous blood donation would appear to be
      unnecessary for the majority of men and the blood loss advantage traditionally
      associated with perineal RP is no longer evident.

PMID- 14693272
TI  - Adenoviral p53 gene transfer in human bladder cancer cell lines: cytotoxicity and
      synergy with cisplatin.
AB  - Mutations of the tumor suppressor gene p53 are common in bladder cancer. To
      determine whether p53 gene transfer would lead to decreased viability of bladder
      cancer cells, we studied the effect of p53 gene transfer in human bladder cancer
      cell lines with either mutant or wild-type p53. Bladder cancer cell lines 5637
      and J82 (which express only mutant p53) and 253J-BV (which expresses wild-type
      p53) were transduced with vectors containing the beta-galactosidase gene (Ad5
      lacZ), wild-type human p53 gene (Ad5CMV-p53), or no foreign gene (DL312 or Ad5
      polyA). X-gal staining of cells exposed to Ad5-lacZ showed that the adenoviral
      vector was capable of transducing each of the cell lines. Increases in p53,
      p21(waf1/cip1) and bax protein were demonstrated following exposure to Ad5CMV
      p53, and there was a dose-dependent increase in the number of apoptotic cells.
      Cell viability was decreased in all three cell lines, although J82 was less
      sensitive than either 5637 or 253J-BV. To determine whether cisplatin increases
      sensitivity of J82 cells to Ad5CMV-p53, we performed median effect analysis for
      cisplatin combined with Ad5CMV-p53 or DL312. The combination index for cisplatin
      plus Ad5CMV-p53 revealed synergy, whereas cisplatin and DL312 were only additive.
      These results suggest that forced p53 gene expression is cytotoxic to human
      bladder cancer cells with either p53 mutant or wild-type background, and that
      combination with cisplatin is a potential method for overcoming resistance.

PMID- 14693274
TI  - Neoadjuvant chemotherapy for bladder cancer.
AB  - While it is now clear that chemotherapy can contribute to improved outcome for
      some patients with muscle invasive bladder cancer, selection criteria for this
      very heterogeneous disease are lacking. The authors make an appeal for a
      biologically (in contrast to anatomically) based staging system, and urge that
      perioperative chemotherapy be given with standard combinations with curative
      intent.

PMID- 14693275
TI  - Chemotherapy and cystectomy for invasive transitional cell carcinoma of bladder.
AB  - Invasive transitional cell bladder cancer is associated with occult metastasis.
      Approximately 50% of patients with clinically localized, invasive bladder cancer
      ultimately die of their disease. Systemic chemotherapy has been combined with
      radical cystectomy in an attempt to improve survival. Phase I and II trials have
      achieved tumor down-staging. Initial randomized trials did not show a
      statistically significant survival benefit from systemic single agent
      chemotherapy. More recently, two multi-center randomized trials have shown a
      significant survival benefit from neoadjuvant combination chemotherapy. Adjuvant
      chemotherapy trials, to date, have failed to show statistically improved
      survival, although most published studies have been methodologically flawed. For
      invasive, clinically nonmetastatic bladder cancer, neo-adjuvant chemotherapy
      followed by radical cystectomy is one of the new standards of care. The role of
      postsurgical systemic chemotherapy appears promising, but has not been proven in
      a randomized trial. Molecular prognostication is now being incorporated into the
      design of clinical trials of adjuvant chemotherapy for bladder cancer.

PMID- 14693276
TI  - If cystectomy is insufficient, what is an urologist to do?
AB  - Tumor free survival after radical cystectomy is stage dependent. In addition,
      other features such as the presence of angioinvasion or micropapillary histology
      also indicate a poor outcome. Failures of definitive therapy by radical
      cystectomy occur most frequently at distant sites and appear to result from
      occult micrometastases present at the time of surgery. These clinical data
      strongly suggest that radical cystectomy provides insufficient treatment for a
      group of patients at high risk for tumor recurrence. Multimodal therapy
      (chemotherapy and surgery) seems to improve outcome in such patients, whether
      given in a neoadjuvant or adjuvant mode. This increased probability of improved
      outcome with multimodal therapy, however, is accompanied by an almost certain
      risk of increased toxicity. The neoadjuvant strategy can deliver systemic
      chemotherapy more reliably and may permit bladder salvage, but adjuvant therapy
      permits patient selection based on pathology results. The most critical issue in
      multimodal therapy is patient selection. The choice of neoadjuvant or adjuvant
      therapy will depend on clinical circumstances, resources, and patient and
      physician preferences.

PMID- 14693296
TI  - Tolerability of short-term, high-dose formoterol in healthy volunteers and
      patients with asthma.
AB  - BACKGROUND: Formoterol is a long-acting (>or=12 hours) beta(2)-receptor agonist
      with a rapid onset of action (1-3 minutes). It is approved in the United States,
      delivered via a single-dose dry-powder inhaler (DPI), for use in combination with
      anti-inflammatory therapy for the maintenance treatment of asthma and for the
      prevention of exercise-induced bronchospasm. Potential exposure of patients to
      higher doses than are currently approved is an important consideration in
      assessing the safety profile of formoterol. OBJECTIVE: This article reviews data
      from clinical trials investigating the effects of short-term use (4-48 hours) of
      high doses of formoterol (maximum, 228 microg). METHODS: Comparative and
      noncomparative studies of the effects of short-term, high-dose formoterol,
      inhaled via metered-dose inhaler (MDI) or single-dose DPI, were identified
      through searches of the literature indexed on MEDLINE, EMBASE, Current Contents,
      and Science Citation Index from their inception through August 15, 2003. RESULTS:
      This review included 1 open-label noncomparative study of high-dose formoterol in
      12 healthy volunteers (mean age, 29 years), 1 placebo-controlled dose-escalation
      study of formoterol in 20 patients with asthma (mean age, 30 years), and 3
      comparative studies of formoterol and short-acting beta(2)-agonists. The latter
      included a dose-escalation study in 13 patients with asthma (mean age, 47.2
      years), a high-dose study in 12 healthy volunteers (mean age, 27 years), and a
      dose-escalation study in 9 children with asthma (mean age, 10 years). In the
      study in healthy volunteers, the metabolic and cardiovascular effects of high
      single doses of formoterol (maximum, 120 microg) were small and had no clinical
      consequences. In the placebo-controlled dose-escalation study in patients with
      asthma, however, the metabolic effects of formoterol at doses from 24 to 96
      microg and the cardiovascular effects of formoterol at doses from 48 to 96 microg
      differed significantly from those of placebo (P < 0.05 to P <0.001) but were
      unlikely to result in clinically significant adverse effects. In the studies
      comparing formoterol with short-acting beta(2)-agonists in patients with stable
      asthma, the cardiovascular and metabolic effects of short-term, high-dose
      formoterol (cumulative dose, up to 228 microg) were comparable to those of high
      dose albuterol (salbutamol) (cumulative dose, up to 3800 microg). Studies of high
      dose formoterol delivered via multidose DPI (not available in the United States)
      have reported a safety profile similar to those of high-dose terbutaline and
      albuterol. CONCLUSION: In studies of the short-term use of high-dose formoterol
      delivered via an MDI or single-dose DPI, this agent had a safety profile
      comparable to that of short-acting beta(2)-agonists.

PMID- 14693297
TI  - The cardiovascular effects of eplerenone, a selective aldosterone-receptor
      antagonist.
AB  - BACKGROUND: The role of the renin-angiotensin-aldosterone system in the
      pathophysiology and treatment of hypertension and heart failure has been
      extensively studied. Angiotensin-converting enzyme inhibitors and angiotensin II
      receptor blockers have been shown to effectively reduce blood pressure, protect
      the kidney, and reduce morbidity and mortality in patients with heart failure.
      Therefore, there is increased interest in the effects of aldosterone and the use
      of aldosterone-receptor antagonists in the treatment of cardiovascular disease.
      Eplerenone is the first selective aldosterone-receptor antagonist approved for
      the treatment of hypertension and left ventricular (LV) dysfunction after acute
      myocardial infarction (AMI). OBJECTIVE: The goal of this article was to review
      the pharmacologic properties, clinical efficacy, and tolerability of eplerenone
      in the treatment of hypertension, LV dysfunction, and proteinuria. METHODS:
      Relevant English-language articles were identified through searches of MEDLINE
      (1966-May 2003), Current Contents, and International Pharmaceutical Abstracts
      (1970-May 2003) using the terms hypertension, heart failure, eplerenone,
      aldosterone, and aldosterone antagonist. Other pertinent publications were
      identified from the reference lists of the identified articles. Information was
      also obtained from abstracts presented at national meetings and data on file with
      the manufacturer. RESULTS: In clinical trials, eplerenone alone and in
      combination with renin-angiotensin blockade significantly reduced both systolic
      and diastolic blood pressure compared with placebo (P < 0.05 to P < 0.001). In
      EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and
      Survival Study), the addition eplerenone to optimal medical therapy reduced
      morbidity and mortality in patients with AMI and LV dysfunction, although the
      incidence of serious hyperkalemia was also significantly greater. In comparisons
      with spironolactone, eplerenone was associated with a lower incidence of
      gynecomastia and other sex hormone-related adverse effects. CONCLUSIONS: Either
      alone or in combination with other antihypertensive agents, eplerenone appears to
      be effective for the treatment of hypertension. Morbidity and mortality were
      reduced when eplerenone was added to standard therapy for LV dysfunction
      complicating AMI. The use of eplerenone for hypertension or heart failure may be
      limited in patients at risk for hyperkalemia.

PMID- 14693298
TI  - Zoledronic acid: a new parenteral bisphosphonate.
AB  - BACKGROUND: Inhibition of bone resorption using bisphosphonates is an important
      step in palliation of complications of advanced cancer, such as hypercalcemia and
      metastatic bone disease. OBJECTIVE: The goal of this article was to describe the
      pharmacologic properties of zoledronic acid (zoledronate) and discuss findings
      from preclinical and clinical studies of its use in skeletal disorders. METHODS:
      Relevant English-language literature was identified using the terms zoledronic
      acid, zoledronate, Zometa, and 118072-93-8 through searches of MEDLINE (1966-June
      2003) and International Pharmaceutical Abstracts (1970-June 2003), and abstract
      proceedings from the American Society of Clinical Oncology (1997-2002). RESULTS:
      Zoledronic acid is a nitrogen-containing bisphosphonate that inhibits bone
      resorption. It is indicated for the treatment of hypercalcemia of malignancy and
      for the treatment of patients with multiple myeloma or documented metastasis from
      solid tumors, in conjunction with standard antineoplastic therapy. The
      recommended dosage is 4 mg via IV over >or= 15 minutes every 3 or 4 weeks.
      Compared with pamidronate 90 mg, zoledronic acid 4 and 8 mg provided a higher
      complete response rate for hypercalcemia of malignancy by day 10 (88.4% and 86.7%
      vs 69.7%; P = 0.002 and P = 0.015) and longer duration of action (median time to
      relapse, 30 and 40 days vs 17 days; P = 0.001 and P = 0.007). In patients with
      breast cancer or multiple myeloma, zoledronic acid was as effective as
      pamidronate in delaying time to a first skeletal-related event (373 days vs 363
      days). In patients with hormone-refractory prostate cancer and bone metastases,
      zoledronic acid 4 mg reduced the proportion of patients who experienced a
      skeletal-related event (33% vs 44% with placebo; P = 0.021) or a skeletal
      fracture (13% vs 22% with placebo; P = 0.015). In patients with bone metastases
      from solid tumors, zoledronic acid delayed the median time to a first skeletal
      related event (230 days vs 163 days with placebo; P = 0.023). Common adverse
      events include fever, nausea, constipation, fatigue, and bone pain. CONCLUSION:
      Zoledronic acid is an effective and generally well-tolerated treatment for
      hypercalcemia of malignancy and skeletal complications of metastatic bone
      disease.

PMID- 14693299
TI  - A multicenter, randomized, double-blind, crossover study of patient preference
      for tadalafil 20 mg or sildenafil citrate 50 mg during initiation of treatment
      for erectile dysfunction.
AB  - BACKGROUND: Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor approved in >30
      countries for the treatment of erectile dysfunction (ED). It has been shown to
      improve erectile function compared with placebo in Phase III studies, but
      clinical experience comparing tadalafil with the PDE5 inhibitor sildenafil
      citrate is lacking. OBJECTIVE: This study compared patient preference for
      tadalafil 20 mg or sildenafil 50 mg during initial treatment for ED. It also
      compared the tolerability of the 2 agents at these doses. METHODS: This
      randomized, double-blind, fixed-dose, 2-period crossover trial took place at 13
      sites in the United States and Germany. Patients were randomized 1:1 to receive 4
      weeks of treatment with tadalafil 20 mg or sildenafil 50 mg, followed by the
      alternative treatment, to be taken as needed up to once daily before sexual
      activity. RESULTS: The study enrolled 215 men with ED, 109 randomized to the
      tadalafil-sildenafil sequence and 106 to the sildenafil-tadalafil sequence. Their
      mean age was 49.8 years; 84.7% were sildenafil naive and 15.3% had undergone a
      previous inadequate trial of sildenafil. Most patients had moderate ED (60.5%) of
      >or=1 year's duration (74.9%). Of 190 evaluable patients, 126 (66.3%) preferred
      to initiate treatment with tadalafil, compared with 64 (33.7%) with sildenafil (P
      < 0.001). Patients' preference did not differ by age, duration of ED, treatment
      sequence, or previous sildenafil exposure. Both medications were well tolerated,
      with no significant differences in the incidence of treatment-emergent adverse
      events. Headache (11.2% tadalafil, 8.8% sildenafil), dyspepsia (6.0% and 4.2%,
      respectively), nasopharyngitis (4.7% and 2.8%), and flushing (2.8% and 4.7%) were
      the most common adverse events. The rate of ocular disturbances was low: 1
      patient experienced intermittent bilateral reduction in visual acuity with
      tadalafil, and 2 exhibited conjunctival hyperemia or eyelid edema with
      sildenafil. CONCLUSIONS: Tadalafil 20 mg was preferred to sildenafil 50 mg for
      the initiation of ED therapy in this study population. Both medications were well
      tolerated.

PMID- 14693300
TI  - Switching patients with erectile dysfunction from sildenafil citrate to
      tadalafil: results of a European multicenter, open-label study of patient
      preference.
AB  - BACKGROUND: Three inhibitors of phosphodiesterase 5 (PDE5) are now available for
      the treatment of erectile dysfunction (ED): sildenafil citrate, vardenafil, and
      tadalafil. Pharmacologic differences between these compounds may result in
      patient preferences for one over another and may influence treatment decisions
      made by the physician and patient. Therefore, clinical research is needed to
      investigate whether individual properties of the PDE5 inhibitors play a role in
      shaping patient preference. OBJECTIVES: The goal of this study was to determine
      what proportion of ED patients currently taking sildenafil would, after a period
      of treatment with tadalafil, elect to resume treatment with sildenafil at the
      customary dose and what proportion would elect a switch to tadalafil 20 mg for a
      longer period. The tolerability of both treatments was also investigated.
      METHODS: This was a short-term, multicenter, open-label, 1-way crossover trial
      conducted in Sweden and Italy. Eligible patients included men aged >or=18 years
      with a minimum 3-month history of ED who had been taking sildenafil at stable
      fixed doses of 25, 50, or 100 mg as needed for at least 6 weeks and up to 24
      weeks. The study consisted of 6 phases: a 1-week screening phase, a 3-week
      sildenafil assessment phase, a 1-week washout phase, a 6-week tadalafil
      initiation phase, a 3-week tadalafil assessment phase, and a 6-month extension
      phase, during which patients received their treatment of choice free of charge.
      The primary outcome measure was the proportion of patients electing to take
      sildenafil or tadalafil during the extension phase. RESULTS: Of 155 men enrolled,
      147 (97.8%) completed the assessment phases of the trial. Of these 147 men, 133
      (90.5%) elected to receive tadalafil in the 6-month extension phase and 14 (9.5%)
      elected to receive sildenafil (P < 0.001). The proportions preferring tadalafil
      to sildenafil were similar irrespective of age group (>or=50 years, 92%; <50
      years, 90%), severity of ED (mild, 95%; moderate, 88%; severe, 96%), etiology of
      ED (psychogenic, 94%; organic, 91%; mixed, 87%), and sildenafil dose at study
      entry (50 mg, 90%; 100 mg, 89%). Both medications were well tolerated. The most
      common treatment-emergent adverse events occurring in >or=2% of patients during
      the tadalafil assessment phase included headache (4.8%), nasal congestion (4.1%),
      dyspepsia (3.4%), flushing (2.7%), back pain (2.0%), diarrhea (2.0%), and nausea
      (2.0%); the most common treatment-emergent adverse events during the sildenafil
      assessment phase were flusing (7.1%), nasal congestion (6.5%), headache (4.5%),
      and nasopharyngitis (3.2%). CONCLUSIONS: In this short-term, open-label study,
      patients who were currently taking sildenafil for ED and then received tadalafil
      preferred to continue oral therapy with tadalafil over sildenafil by a ratio of
      approximately 9:1. Although the study sought to mimic the experience of actual
      patients receiving treatment for ED, the results are subject to potential
      limitations due to the design of the study, which included differences in dosing
      instructions and dosages for sildenafil and tadalafil. Both sildenafil and
      tadalafil were well tolerated.

PMID- 14693301
TI  - A multicenter, randomized, double-blind clinical trial comparing the low-density
      lipoprotein cholesterol-lowering ability of lovastatin 10, 20, and 40 mg/d with
      fluvastatin 20 and 40 mg/d.
AB  - BACKGROUND: The available statin drugs have similar pharmacodynamic properties
      but are not equal in low-density lipoprotein cholesterol (LDL-C)-lowering
      efficacy. OBJECTIVE: The aim of this study was to compare the effects of
      lovastatin and fluvastatin in lowering LDL-C. METHODS: This was a prospective,
      randomized, double-blind study of patients aged >20 years with primary
      hypercholesterolemia conducted at 44 clinical sites across the United States.
      After a 6-week National Cholesterol Education Program (NCEP) Step I diet lead-in
      period in patients taking lipid-lowering drugs at screening, patients were
      randomized to receive lovastatin 10, 20, or 40 mg/d or fluvastatin 20 or 40 mg/d
      (the doses available at the time the study was conducted) for 6 weeks. Patients
      not taking lipid-lowering drugs at screening and who had been following the Step
      I diet for at least 6 weeks proceeded to the treatment phase. All patients
      received instruction for a Step I diet, which they followed throughout the
      treatment phase. After the treatment period, total cholesterol (TC), high-density
      lipoprotein cholesterol (HDL-C), LDL-C, and triglycerides were measured, and
      TC:HDL-C and LDL-C:HDL-C ratios were calculated. RESULTS: A total of 838 patients
      (476 men, 362 women; mean [SD] age, 59 [12] years) were included in the study.
      Lovastatin 20 and 40 mg/d significantly reduced mean LDL-C compared with the same
      dosages of fluvastatin. TC and the LDL-C:HDL-C ratio decreased more with
      lovastatin than with fluvastatin at a given dose level. Approximately 50% of
      patients treated with lovastatin 20 and 40 mg/d compared with approximately 25%
      treated with fluvastatin 20 and 40 mg/d reached NCEP Adult Treatment Panel II LDL
      C goals. CONCLUSION: In this small study population of patients with primary
      hypercholesterolemia taking lipid-lowering drugs, short-term (6-week) treatment
      with lovastatin was more efficacious than fluvastatin in lowering cholesterol
      levels and reaching LDL-C treatment goals.

PMID- 14693302
TI  - Effects of rosiglitazone maleate when added to a sulfonylurea regimen in patients
      with type 2 diabetes mellitus and mild to moderate renal impairment: a post hoc
      analysis.
AB  - BACKGROUND: Patients with type 2 diabetes mellitus (DM) and renal impairment
      whose disease is inadequately controlled on a sulfonylurea (SU) have limited oral
      combination treatment options. OBJECTIVE: This post hoc analysis assesses the
      efficacy and tolerability of the insulin sensitizer rosiglitazone maleate (RSG)
      when added to an SU treatment regimen in patients with type 2 DM with mild to
      moderate renal impairment that is inadequately controlled by SU monotherapy.
      METHODS: Data were pooled from 3 randomized, double-blind, placebo-controlled,
      parallel-group studies in which RSG or placebo was added to an SU (glibenclamide,
      gliclazide, or glipizide) treatment regimen for a period of 6 months. Patients
      were subcategorized as having mild to moderate renal impairment or normal renal
      function based on a baseline creatinine clearance rate of 30 to 80 mL/min or >80
      mL/min, respectively, as estimated by the Cockcroft-Gault equation. RESULTS: The
      population studied comprised 824 patients, 62% men and 38% women, aged 32 to 81
      years, of whom 301 had mild to moderate renal impairment and 523 had normal renal
      function. In patients with and without renal impairment, glycemia was improved in
      the SU + RSG-treated group compared with the SU + placebo-treated group. The
      observed treatment differences between the groups were -2.6 mmol/L for fasting
      plasma glucose and -1.1% for glycosylated hemoglobin (for both renally impaired
      and nonimpaired patients). For patients receiving SU + RSG, little difference in
      the safety profile was found between patients with and without renal impairment.
      CONCLUSION: RSG was effective and well tolerated when added to SU therapy in this
      population of patients with mild to moderate renal impairment.

PMID- 14693303
TI  - A randomized, double-blind, active-controlled, parallel-group comparison of
      valsartan and amlodipine in the treatment of isolated systolic hypertension in
      elderly patients: the Val-Syst study.
AB  - BACKGROUND: Some antihypertensive therapies are limited by dose-dependent adverse
      effects (AEs). The angiotensin II receptor blocker valsartan has been shown to
      reduce blood pressure (BP) in a dose-related manner with minimal dose-limiting
      AEs. Amlodipine besylate is a potent dihydropyridine calcium channel blocker also
      with dose-related antihypertensive efficacy, but with possible dose-limiting AEs,
      particularly peripheral edema. OBJECTIVES: This study compared the risk/benefit
      profiles of valsartan and amlodipine in elderly patients who have isolated
      systolic hypertension (ISH). METHODS: This 24-week, randomized, double-blind,
      active-controlled, titration-to-effect, parallel-group study was conducted at 35
      outpatient centers in Italy. Elderly (aged 60-80 years) patients with ISH
      received oral treatment with valsartan 80-mg capsules or amlodipine 5-mg capsules
      once daily. After 8 weeks of treatment, the dose of the patients with poorly
      controlled systolic BP (SBP) was titrated to 160 mg (valsartan) or 10 mg
      (amlodipine) once daily. At week 16, if trough SBP was still not adequately
      controlled, a low-dose diuretic (hydrochlorothiazide [HCTZ] 12.5 mg) was added to
      the treatment regimen for an additional 8 weeks. Tolerability was assessed at all
      study visits using physical examination and patient interview. RESULTS: Of 421
      randomized patients (231 women, 190 men; mean [SD] age, 69 [6] years), 208 were
      included in the valsartan group, and 213 in the amlodipine group. The efficacy of
      valsartan-based treatment. in reducing SBP was similar to that of amlodipine
      based treatment. With doubled doses, efficacy (change in SBP) increased
      significantly from baseline (both P < 0.01). The frequency of AEs doubled with
      amlodipine 10 mg but was not clinically relevant with valsartan 160 mg. Overall,
      AEs were observed in 31.9% of those receiving amlodipine versus 20.2% of the
      patients receiving valsartan (P < 0.003), with peripheral edema rates of 26.8%
      and 4.8%, respectively (P < 0.001). CONCLUSIONS: In this study population of
      elderly patients with ISH, valsartan-given alone or in combination with HCTZ 12.5
      mg-showed similar efficacy but better tolerability than amlodipine-based
      treatment.

PMID- 14693304
TI  - A multicenter retrospective cohort study of practice patterns and clinical
      outcomes of the use of darbepoetin alfa and epoetin alfa for chemotherapy-induced
      anemia.
AB  - BACKGROUND: Darbepoetin alfa is the second erythropoietic protein to be approved
      for the treatment of chemotherapy-induced anemia (CIA). In the clinical setting,
      darbepoetin alfa can be administered less frequently than epoetin alfa with
      similar efficacy. Practice patterns and outcomes associated with the use of
      darbepoetin alfa and epoetin alfa in the clinical setting have not been reported.
      OBJECTIVE: This study compared practice patterns and clinical outcomes of the use
      of darbepoetin alfa and epoetin alfa for CIA at oncology practices in the United
      States. METHODS: This was a multicenter retrospective cohort study. Data were
      abstracted from the medical charts of consecutive patients who began darbepoetin
      alfa treatment between August 1 and October 4, 2002, or epoetin alfa treatment
      between April 1 and July 31, 2002, and were receiving concurrent chemotherapy.
      These data were used to determine the initial dose and dosing schedule, dose
      changes, and changes in hemoglobin concentrations after 4, 8, and 12 weeks of
      treatment, adjusted for red blood cell (RBC) transfusions, and the incidence of
      RBC transfusions over time. To minimize potential bias, the study protocol
      defined specific end points and prespecified analytic techniques for assessing
      clinical outcomes with the 2 agents. RESULTS: The records of 1391 patients from
      16 community and hospital outpatient oncology clinics were abstracted. Of these,
      1293 patients (93.0%) received only 1 erythropoietic agent (darbepoetin alfa, 735
      [56.8%]; epoetin alfa, 558 [43.2%]); the remainder received both agents. In the
      patients who received darbepoetin alfa, most (553 [75.2%]) received an initial
      dosage of 200 microg q2wk. A similar proportion (414 [74.2%]) received epoetin
      alfa at an initial dosage of 40,000 U qwk. As these were the regimens for the
      majority of patients whose records were abstracted, the results reported here are
      for these patients. The dose was increased in 63 darbepoetin alfa recipients
      (11.4%) and 58 epoetin alfa recipients (14.0%) at a median of 7 weeks. After 12
      weeks, the 2 groups had an identical mean imputed change from baseline in
      hemoglobin concentration (1.0 g/dL), and the incidence of RBC transfusions during
      treatment was also similar between groups (darbepoetin alfa, 44553 [8.0%];
      epoetin alfa, 39414 [9.4%]). CONCLUSIONS: Darbepoetin alfa 200 microg q2wk was
      used as a standard regimen for CIA at the 16 US oncology practices participating
      in this study. It appeared to be as effective as epoetin alfa 40,000 U qwk, with
      a reduced frequency of dosing.

PMID- 14693305
TI  - Efficacy and tolerability of oral stevioside in patients with mild essential
      hypertension: a two-year, randomized, placebo-controlled study.
AB  - BACKGROUND: Stevioside, a natural glycoside isolated from the plant Stevia
      rebaudiana Bertoni, has been used as a commercial sweetening agent in Japan and
      Brazil for >20 years. Previous animal and human studies have indicated that
      stevioside has an antihypertensive effect. OBJECTIVES: This study was undertaken
      to investigate the long-term (2-year) efficacy and tolerability of stevioside in
      patients with mild essential hypertension. Secondary objectives were to determine
      the effects of stevioside on left ventricular mass index (LVMI) and quality of
      life (QOL). METHODS: This was a multicenter, randomized, double-blind, placebo
      controlled trial in Chinese men and women aged between 20 and 75 years with mild
      essential hypertension (systolic blood pressure [SBP] 140-159 mm Hg and diastolic
      blood pressure [DBP] 90-99 mm Hg). Patients took capsules containing 500 mg
      stevioside powder or placebo 3 times daily for 2 years. Blood pressure was
      measured at monthly clinic visits; patients were also encouraged to monitor blood
      pressure at home using an automated device. LVMI was determined by 2-dimensional
      echocardiography at baseline and after 1 and 2 years of treatment. QOL was
      assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey.
      Electrocardiographic, laboratory, and QOL parameters were assessed at the
      beginning of treatment, and at 6 months, 1 year, and 2 years. RESULTS: One
      hundred seventy-four patients (87 men, 87 women) were enrolled in the study, and
      168 completed it: 82 (42 men, 40 women; mean [SD] age, 52 [7] years) in the
      stevioside group and 86 (44 women, 42 men; mean age, 53 [7] years) in the placebo
      group. After 2 years, the stevioside group had significant decreases in mean (SD)
      SBP and DBP compared with baseline (SBP, from 150 [7.3] to 140 [6.8] mm Hg; DBP,
      from 95 [4.2] to 89 [3.2] mm Hg; P < 0.05) and compared with placebo (P < 0.05).
      Based on patients' records of self-monitored blood pressure, these effects were
      noted beginning approximately 1 week after the start of treatment and persisted
      throughout the study. There were no significant changes in body mass index or
      blood biochemistry, and the results of laboratory tests were similar in the 2
      groups throughout the study. No significant difference in the incidence of
      adverse effects was noted between groups, and QOL scores were significantly
      improved overall with stevioside compared with placebo (P < 0.001). Neither group
      had a significant change in mean LVMI. However, after 2 years, 6 of 52 patients
      (11.5%) in the stevioside group had left ventricular hypertrophy (LVH), compared
      with 17 of 50 patients (34.0%) in the placebo group (P < 0.001). Of those who did
      not have LVH at baseline, 3 of 46 patients (6.5%) in the stevioside group had
      developed LVH after 2 years, compared with 9 of 37 patients (24.3%) in the
      placebo group (P < 0.001). CONCLUSIONS: In this 2-year study in Chinese patients
      with mild hypertension, oral stevioside significantly decreased SBP and DBP
      compared with placebo. QOL was improved, and no significant adverse effects were
      noted.

PMID- 14693306
TI  - Change in opioid use after the initiation of gabapentin therapy in patients with
      postherpetic neuralgia.
AB  - BACKGROUND: Postherpetic neuralgia (PHN) is a chronic painful disorder that
      sometimes develops after an acute episode of herpes zoster infection (shingles)
      and can be difficult to treat. Although opioids are sometimes effective for
      chronic neuropathic pain, adverse effects are common, particularly among the
      elderly, and may cause many patients to discontinue therapy. OBJECTIVE: This
      study examined changes in opioid use after the initiation of gabapentin therapy
      in patients with PHN. METHODS: A health insurance claims database was used to
      identify all persons aged >or= 18 years who began therapy with gabapentin in 2000
      or 2001 and had either (1) >or=2 medical claims with a diagnosis of PHN during
      the 6-month period before the first receipt of gabapentin (index date) or (2) 1
      such claim <or=14 days before the index date. Persons who were not continuously
      eligible for medical and drug benefits for 6 months before and after the index
      date (pretreatment and follow-up, respectively) were dropped from the study
      sample. Use of opioids, including both short- and long-acting formulations, was
      compared between pretreatment and follow-up. Patients were stratified in the
      study analyses by whether they received 1 or >or=2 prescriptions for gabapentin.
      RESULTS: Forty-five patients with PHN began therapy with gabapentin during the
      period of interest; 35 (77.8%) received >or=2 prescriptions for gabapentin. The
      proportion of patients receiving opioids decreased significantly between
      pretreatment and follow-up (from 88.9% to 71.1%; P = 0.03); the mean number of
      opioid prescriptions per patient also decreased significantly (from 3.9 to 3.0; P
      = 0.03). These reductions were observed only in patients who received >or=2
      prescriptions for gabapentin; there was no significant change in opioid use among
      those who received only 1 prescription for gabapentin. CONCLUSION: In this study,
      initiation of gabapentin therapy in patients with PHN was associated with a
      reduction in the use of opioid analgesics.

PMID- 14693307
TI  - Metabolism, excretion, and pharmacokinetics of rosuvastatin in healthy adult male
      volunteers.
AB  - BACKGROUND: Rosuvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A-reductase
      inhibitor, or statin, that has been developed for the treatment of dyslipidemia.
      OBJECTIVE: This study assessed the metabolism, excretion, and pharmacokinetics of
      a single oral dose of radiolabeled rosuvastatin ([14C]-rosuvastatin) in healthy
      volunteers. METHODS: This was a nonrandomized, open-label, single-day trial.
      Healthy adult male volunteers were given a single oral dose of [14C]-rosuvastatin
      20 mg (20 mL [14C]-rosuvastatin solution, nominally containing 50 microCi
      radioactivity). Blood, urine, and fecal samples were collected up to 10 days
      after dosing. Tolerability assessments were made up to 10 days after dosing
      (trial completion) and at a follow-up visit within 14 days of trial completion.
      RESULTS: Six white male volunteers aged 36 to 52 years (mean, 43.7 years)
      participated in the trial. The geometric mean peak plasma concentration (C(max))
      of rosuvastatin was 6.06 ng/mL and was reached at a median of 5 hours after
      dosing. At C(max), rosuvastatin accounted for approximately 50% of the
      circulating radioactive material. Approximately 90% of the rosuvastatin dose was
      recovered in feces, with the remainder recovered in urine. The majority of the
      dose (approximately 70%) was recovered within 72 hours after dosing; excretion
      was complete by 10 days after dosing. Metabolite profiles in feces indicated that
      rosuvastatin was excreted largely unchanged (76.8% of the dose). Two metabolites
      rosuvastatin-5S-lactone and N-desmethyl rosuvastatin-were present in excreta.
      [14C]-rosuvastatin was well tolerated; 2 volunteers reported 4 mild adverse
      events that resolved without treatment. CONCLUSIONS: The majority of the
      rosuvastatin dose was excreted unchanged. Given the absolute bioavailability
      (20%) and estimated absorption (approximately 50%) of rosuvastatin, this finding
      suggests that metabolism is a minor route of clearance for this agent.

PMID- 14693308
TI  - A multicenter, randomized, open-label, comparative, two-period crossover trial of
      preference, efficacy, and safety profiles of a prefilled, disposable pen and
      conventional vial/syringe for insulin injection in patients with type 1 or 2
      diabetes mellitus.
AB  - BACKGROUND: The accuracy and convenience of pen devices for insulin injection
      have improved quality of life for patients with insulin-treated diabetes mellitus
      (DM). Prefilled, disposable pens have the advantage of simplicity, with minimal
      training and attention required and no installation of new cartridges necessary.
      OBJECTIVE: The aim of this study was to assess patient preference, efficacy, and
      safety profiles of a prefilled, disposable pen (FlexPen) and conventional
      vial/syringe injection method for insulin injection therapy among patients with
      DM. METHODS: In a multicenter, randomized, open-label, crossover study, patients
      with type 1 or 2 DM were transferred from previous QD or BID conventional insulin
      therapy to a mixture of 70% insulin aspart protamine suspension and 30% insulin
      aspart injection (NovoLog Mix 7030) for 4 weeks of dose optimization using their
      usual type of syringe. Patients were then randomly assigned to use either
      vial/syringe or a prefilled, disposable pen to inject the biphasic insulin aspart
      7030 mixture for the next 4 weeks, followed by 4 weeks of use of the other
      injection device. Efficacy, safety profiles, and patient preference for the
      delivery systems were compared. RESULTS: A total of 121 patients (mean [SD] age,
      57.0 [12.4] years; age range, 28-81 years; mean [SD] body mass index, 31 [5.5]
      kg/m(2)) were enrolled. One hundred three patients completed the study. Seventy
      four percent of patients (78105) indicated a preference for the pen over the
      vial/syringe method (95% CI, 71%-87%), compared with 20% (21105) who preferred
      the vial/syringe. Eighty-five percent (88104) considered the pen more discreet
      for use in public (compared with 9% [9104] for the vial/syringe), 74% (77104)
      considered it easier to use overall (compared with 21% [22104] for the
      vial/syringe), and 85% (89105) found the insulin dose scale on the pen easier to
      read (compared with 10% [10105] for the vial/syringe). Patients had statistically
      significant improvement in glycosylated hemoglobin values during the study (P <
      0.05). No statistically significant differences in fasting plasma glucose, mean 4
      point blood glucose profiles, or serum fructosamine values were found between
      groups. Overall, the safety profiles during treatment periods with the pen were
      comparable to those with the vial/syringe. CONCLUSIONS: In this trial,
      differences in efficacy and safety profiles between the vial/syringe and
      prefilled, disposable pen appeared negligible. However, more patients expressed a
      preference to continue use of the pen.

PMID- 14693310
TI  - The effects of intramuscular interferon beta-Ia in patients at high risk for
      development of multiple sclerosis: a post hoc analysis of data from CHAMPS.
AB  - BACKGROUND: In the Controlled High Risk Subjects Avonex Multiple Sclerosis
      Prevention Study (CHAMPS), intramuscular (IM) interferon beta-1a (IFNbeta-1a)
      delayed the development of clinically definite multiple sclerosis (CDMS) in
      patients with a single demyelinating event who had magnetic resonance imaging
      (MRI) evidence of previous subclinical disease activity (defined as >or=2 T2
      weighted hyperintense lesions, 1 of which was periventricular or ovoid, on
      unenhanced MRI scans). OBJECTIVE: This post hoc analysis was conducted to assess
      the effects of IM IFNbeta-1a on delaying the development of CDMS in a subgroup of
      CHAMPS patients who met a more stringent definition of high risk than was used in
      that trial. METHODS: Patients from the overall CHAMPS population were included in
      the present analysis if they had >or=9 T2-weighted hyperintense lesions and >or=1
      gadolinium-enhanced lesion on the baseline MRI scan. The cumulative probability
      of developing CDMS in each treatment group was calculated using the Kaplan-Meier
      product-limit method and compared using the log-rank test. The actual proportions
      of patients who developed CDMS in each treatment group were calculated and
      compared using the chi-square test. RESULTS: Ninety-one patients met the more
      stringent definition of high risk and were included in the subgroup analysis.
      Fifty-one patients (56.0%) received IFNbeta-1a 30 microg IM once weekly and 40
      (44.0%) received placebo. Baseline demographic and clinical characteristics were
      similar between the 2 groups. Seventy-four patients (81.3%) were female, 80
      (87.9%) were white, and the mean age was 33.0 years. Overall, IM IFNbeta-1a
      reduced the rate of development of CDMS by 66% compared with the placebo group (P
      = 0.002, log-rank test) over the 3-year follow-up period. At 2 years, the Kaplan
      Meier estimate of the cumulative probability of developing CDMS was 21% in the IM
      IFNbeta-1a group and 56% in the placebo group, representing a 63% reduction in
      risk for CDMS with IFNbeta-1a (P = 0.002, log-rank test). The results based on
      the actual proportions of patients developing CDMS were similar to the Kaplan
      Meier estimates. CONCLUSIONS: The results of this subgroup analysis are
      compatible with IM IFNbeta-1a reducing the risk of a second demyelinating event
      in patients meeting the more stringent definition of high risk. Although the
      treatment effect of IFNbeta-1a was significant in both the overall CHAMPS
      population (44% risk reduction vs placebo; P = 0.002) and in this high-risk
      subgroup (66%), the results of the present analysis suggest that the magnitude of
      treatment benefit with IFNbeta-1a may be greater in patients with more disease
      activity, as measured by MRI parameters.

PMID- 14693309
TI  - Once-daily fixed-combination irbesartan 300 mg/ hydrochlorothiazide 25 mg and
      circadian blood pressure profile in patients with essential hypertension.
AB  - BACKGROUND: More than 60% of patients with hypertension included in morbidity and
      mortality trials needed >or=2 drugs to achieve a substantial, sustained reduction
      in blood pressure. Tolerable combinations using higher doses of antihypertensive
      drugs are frequently required to control blood pressure. OBJECTIVE: The goal of
      this study was to assess the effect of a once-daily fixed combination of
      irbesartan 300 mg/hydrochlorothiazide (HCTZ) 25 mg on the circadian blood
      pressure profile in patients with essential hypertension that was not controlled
      with full-dose single therapy or low-dose combined therapy. METHODS: Study
      patients were recruited consecutively from the outpatient hypertension clinics of
      3 university hospitals in Spain. After a 1-week washout period, patients with a
      mean daytime blood pressure >135/85 mm Hg were treated with irbesartan 300
      mg/HCTZ 25 mg once daily for 12 weeks. Twenty-four-hour ambulatory blood pressure
      monitoring was performed at the end of the washout period and during the last
      week of treatment. RESULTS: Fifty-seven patients with essential hypertension (28
      men, 29 women) were enrolled; their mean (SD) age was 60.4 (7.2) years (range, 45
      78 years). After treatment, a significant reduction in both clinic and ambulatory
      mean (SD) blood pressure values was observed in the whole group of 57 patients
      (from 146.0 [11.0] mm Hg to 123.3 [13.3] mm Hg, P < 0.001 for 24-hour systolic
      blood pressure [SBP]; from 89.9 [8.2] mm Hg to 76.5 [9.4] mm Hg, P < 0.001 for 24
      hour diastolic blood pressure [DBP]. The mean lowering of ambulatory SBP and DBP
      at peak was 25.2 (14.5) mm Hg and 14.7 (9.5) mm Hg, respectively, and at trough,
      22.3 (18.3) mm Hg and 12.3 (10.9) mm Hg. The trough-to-peak ratio of the group
      was 0.92 for SBP (0.97 in responders) and 0.84 for DBP (0.89 in responders). The
      smoothness index, calculated as the mean of all individual values, was 1.7 (1.0)
      for SBP (1.8 [0.9] in responders) and 1.3 (0.8) for DBP (1.5 [0.6] in
      responders). Seven side effects in 6 patients were reported. No metabolic changes
      were observed, and no patient discontinued the study because of treatment-related
      adverse effects. CONCLUSIONS: The fixed combination of irbesartan 300 mg/HCTZ 25
      administered once daily produced a crude meaningful effect in reducing 24-hour
      blood pressure and was well tolerated. The circadian profile was preserved, as
      shown by trough-to-peak ratios and smoothness index values for both SBP and DBP.

PMID- 14693311
TI  - Bioequivalence and other unresolved issues in generic drug substitution.
AB  - BACKGROUND: Substitution of generic drugs for brand-name products is highly
      controversial and often is met with suspicion by health care providers and
      patients. Historically, the debate has focused on the issue of bioequivalence,
      and clinical practice has identified a number of drug classes for which generic
      substitution should be approached with caution. Current bioequivalence
      requirements are based on a measure of average bioequivalence; however, there are
      fears that use of this measure may be inappropriate in the case of a drug with a
      narrow or wide therapeutic range or high intrasubject or intersubject
      variability. Under these circumstances, measures of individual and population
      bioequivalence are proposed to be more accurate than measures of average
      bioequivalence. OBJECTIVE: This paper addresses issues of bioequivalence and
      other concerns with generic drug substitution. METHODS: I conducted a MEDLINE
      search of the English-language literature containing the key terms generic,
      multisource, quality, and brand and published between 1973 and 2003. The names of
      branded pharmaceuticals whose patents had recently expired (eg, Ventolin HFA,
      Adalat, Capoten, Tagamet HB 200, and Valium) also were used to search for
      articles on generic substitution. Reference lists of relevant articles also were
      searched. Bioequivalence issues are presented together with more general concerns
      over generic drug substitution, such as consumer perception of risk, differences
      in product and packaging appearance, and differences in excipients. RESULTS: The
      literature reviewed act to highlight a number of different drug categories and
      patient subpopulations for which generic substitution can still prove to be
      problematic. CONCLUSION: I recommend that health care providers continue to
      exercise caution in the consideration of generic drug substitution under certain
      circumstances.

PMID- 14693312
TI  - (Unlearned) lessons from John Graunt and Kenneth Rothman: a "CLASSic" example.
AB  - This commentary reviews the work of John Graunt and Kenneth J. Rothman on
      statistical significance and the need for prespecification of study end points.
      The authors argue that it is dangerous to substitute oversimplifications based
      exclusively on whether a result has reached statistical significance for a
      rational process of causal inference. An example is given based on the Celecoxib
      Long-term Arthritis Safety Study.

PMID- 14693314
TI  - Public-private partnerships at the National Institutes of Health: from discovery
      to commercialization.

PMID- 14693315
TI  - Cost-effectiveness of almotriptan and rizatriptan in the treatment of acute
      migraine.
AB  - BACKGROUND: Migraine is a common disorder that costs US employers billions of
      dollars each year in missed workdays and reduced productivity. Seven triptans,
      including almotriptan and rizatriptan, are recommended as first-line therapy for
      acute migraine. OBJECTIVE: The aim of this study was to assess the relative cost
      effectiveness of almotriptan and rizatriptan in the treatment of acute migraine.
      METHODS: A model was built to compare almotriptan 12.5 mg and rizatriptan 10 mg
      for the treatment of a single, acute migraine attack. Cost-effectiveness (in year
      1999 US dollars) was evaluated from the perspective of a US health care payer.
      Mean and incremental cost-effectiveness ratios (CERs) were calculated. The
      effectiveness measure was the proportion of patients who achieved sustained
      freedom from pain with no adverse events (SNAE). Data on sustained pain-free
      outcomes and adverse-event rates were obtained from a meta-analysis of oral
      triptan trials. Efficacy and tolerability were assumed to be independent in the
      base-case scenario, so the total direct cost of treating a single migraine attack
      was calculated, adding drug costs to health service costs per attack. RESULTS: In
      the base-case analysis, the mean CERs for almotriptan 12.5 mg and rizatriptan 10
      mg were 91.12 dollars and 131.26 dollars, respectively, per attack at which SNAE
      was achieved after treatment. The incremental CER for almotriptan (compared with
      rizatriptan 10 mg) was 6.94 dollars per additional SNAE achieved. The economic
      benefit of almotriptan 12.5 mg was robust in a range of sensitivity analyses.
      CONCLUSION: Almotriptan 12.5 mg was more cost-effective than rizatriptan 10 mg
      for the treatment of acute migraine in this analysis based on published data.

PMID- 14693316
TI  - Measuring satisfaction with migraine treatment: expectations, importance,
      outcomes, and global ratings.
AB  - BACKGROUND: Patients tend to express high satisfaction with treatment using
      global rating scales. Previous work in health services, marketing, and operations
      research suggested that global ratings of satisfaction need to account for
      multiple influences and differing patient values. Prior qualitative work with
      patients and clinicians supported a 4-part model that incorporates the gap
      between expectations and outcomes of treatment and accounts for the relative
      importance of different treatment attributes. OBJECTIVE: The aim of this work ws
      to generate a small experimental data set to develop and evaluate the potential
      usefulness of the conceptual model and scoring algorithm for the application of
      this new measurement strategy, the Migraine Treatment Satisfaction Measure
      (MTSM). METHODS: Before treatment, migraine patients who were beginning a new
      prescription for headache rated their expectations and the importance of 9
      attributes of treatment: pain relief, speed of relied, freedom from pain,
      additional symptoms, confidence in treatment, disruption in life, dosing, freedom
      from relapse, and ease of use. After treatment, patients rates outcomes on these
      9 attributes and provided global satisfaction ratings. Weights reflecting the gap
      between expectations and outcomes and the importance ratings were applied to
      these global ratings after treatment to produce the MTSM score. The weighted
      rating scales were then tested for internal consistency, reliability, and
      construct validity using the Short-Form 36-item Health Survey (SF-36), 24-hour
      Migraine Quality of Life Questionnaire (MQoLQ), a measure of symptom
      bothersomeness, and a measure of migraine intensity. RESULTS: Forty-eight
      patients were screened and 29 patients completed this pilot study. Internal
      consistency of coefficients exceeded 0.90 for all 4 components of the MTSM
      (patients' expectations of treatment, ratings of the importance of individual
      attributes of treatment, assessments of outcome on each attribute, and global
      treatment satisfaction ratings). Derived or weighted scores expanded the
      distribution of unweighted global satisfaction ratings and improved statistical
      performance by reducing variability (from 20.5 to 14.8) for overall score).
      Hypothesized associations were confirmed between the MTSM, SF-36, MQoLQ, symptom
      bothersomeness, and migraine intensity. CONCLUSION: The 4-part conceptual model
      reflecting multiple attributes of treatment and preliminary scoring system for
      the MTSM generated satisfaction scores that improved discrimination among
      patients. Further validation is warranted.

PMID- 14693317
TI  - A retrospective cohort study of correlates of response to pharmacologic therapy
      for hyperlipidemia in members of a managed care organization.
AB  - BACKGROUND: Few studies have examined the effectiveness of statins in a managed
      care setting. OBJECTIVE: The aim of this study was to identify demographic,
      clinical, and pharmacotherapy-related factors associated with response to drug
      therapy for hyperlipidemia among members of a managed care organization. METHODS:
      Claims data from a large US managed care organization from July 1, 1998, through
      June 30, 2000, were analyzed for adult members with continuous enrollment, >or=1
      prescription drug claim, >or=2 sets of fasting low-density lipoprotein
      cholesterol (LDL-C) laboratory results, and no lipid-lowering prescription claims
      at any time <or=12 months before the date of the first set of LDL-C laboratory
      results. Relative lipid-lowering regimen efficacy categories were created based
      on percentage reduction in LDL-C listed in product package inserts (low, <or=30%;
      moderate, 31%-40%; high, >or=41%). Multiple regression and logistic regression
      models were developed to identify significant predictors of percentage change in
      LDL-C from baseline and of >or=10% reduction in LDL-C. RESULTS: A total of 6247
      members met the inclusion criteria. The mean (SD) age was 59.6 (12.4) years
      (range, 21-93 years), and 3003 individuals (48.1%) were women. Furthermore, 337
      members (5.4%) received high-efficacy statins, 2633 (42.1%) received moderate
      efficacy statins, 934 (15.0%) received low-efficacy statins, and 86 (1.4%)
      received low-efficacy lipid-lowering drugs from other therapeutic classes during
      the study period. Compliance with therapy was high (range, 85%-92%), and upward
      titration of therapy was found in only 160 members (2.6%). Multiple regression
      analysis indicated that receiving statin therapy compared with other lipid
      lowering therapy was a significant predictor of percentage reduction in LDL-C (P
      < 0.001). Logistic regression analysis indicated that compared with high-efficacy
      statin regimens, low-efficacy statin regimens (odds ratio [OR] = 0.619; 95% CI,
      0.436-0.877) and low-efficacy regimens from other therapeutic classes (OR =
      0.171; 95% CI, 0.099-0.295) were less effective in lowering LDL-C by >or=10%.
      Similar results were observed for subanalyses of subjects with diabetes mellitus
      or coronary heart disease (CHD); individuals who received more efficacious statin
      regimens were more likely to reach the National Cholesterol Education Program
      Adult Treatment Panel II LDL-C goal of <or=100 mg/dL (P < 0.05 for moderate- or
      low-efficacy regimens vs high-efficacy statins in each model). CONCLUSION: The
      results of the present study suggest that improvement is needed in hyperlipidemia
      management, especially in identification and use of lipid-lowering therapy in
      individuals at high risk for CHD.

PMID- 14693318
TI  - Predictors of medication adherence and associated health care costs in an older
      population with type 2 diabetes mellitus: a longitudinal cohort study.
AB  - BACKGROUND: The cost of treating diabetes mellitus and its complications is high
      (91.8 billion dollars in the United States in 2002). It is important to
      understand predictors of adherence to therapy with different antidiabetic
      medications and to determine the relationships between adherence and health care
      service utilization in older adults (aged >or=65 years) with type 2 diabetes
      mellitus. OBJECTIVE: The aim of this study was to examine the relationship
      between self-reported health status data, subsequent antidiabetic medication
      adherence, and health care service utilization in older adults with type 2
      diabetes mellitus in a managed care setting. METHODS: This was a longitudinal
      cohort study of older adults in the south-eastern United States with type 2
      diabetes mellitus who completed a health status assessment, used antidiabetic
      medications, and were enrolled in a health maintenance organization (HMO)
      continuously for 1 to 5 years. The baseline assessment included questions related
      to demographics, health care service utilization in the year before enrollment,
      lifestyle, and quality of life. Demographic, clinical, and utilization-related
      economic variables were also retrieved from the administrative claims data of the
      patients' HMO. Prescription refill patterns were used to measure adherence.
      Associations were examined with a sequential, mixed-model, regression approach.
      Model appropriateness was tested via sensitivity analyses with logged and
      unlogged dependent variables. RESULTS: A total of 775 patients were included.
      Increased comorbidity severity and an emergency room visit during the year prior
      to enrollment in a Medicare HMO were independently associated with decreased
      antidiabetic medication possession ratios (MPRs) after enrollment. After
      controlling for type of medication therapy and other variables, increased
      antidiabetic MPR remained the strongest predictor of decreased total annual
      health care costs (8.6% to 28.9% decrease in annual costs with every 10% increase
      in MPR; P < 0.001). Adherence to anti-diabetic medications was a greater driver
      of cost reduction than other concurrent medications (eg, statins) in this
      population. CONCLUSIONS: This study found strong associations between decreased
      anti-diabetic medication adherence and increased health care service utilization
      in older adults with type 2 diabetes mellitus in a managed care setting. Health
      status assessments completed at time of enrollment had the potential to identify
      enrollees with higher risk for both nonadherent behaviors and poor health-related
      outcomes.

PMID- 14693319
TI  - Cost-effectiveness of anastrozole versus tamoxifen as first-line therapy for
      postmenopausal women with advanced breast cancer.
AB  - BACKGROUND: In a recent trial of first-line therapy in 353 postmenopausal women
      with predominantly hormone receptor-positive advanced breast cancer (the North
      American trial), anastrozole 1 mg QD produced a significantly longer time to
      disease progression (TTP) than tamoxifen 20 mg QD (11.1 months vs 5.6 months; P =
      0.005). Both treatments were well tolerated, but there were fewer thromboembolic
      events and a reduced incidence of vaginal bleeding with anastrozole. OBJECTIVE:
      The aim of this study was to conduct an economic analysis of anastrozole versus
      tamoxifen based on data from the North American trial. METHODS: Quality-adjusted
      TTP (QATTP) was determined by combining TTP values with uniform or graded weights
      for adverse events using the Quality-adjusted Time Without Symptoms and Toxicity
      method. Direct health care costs before and after disease progression were
      determined from the perspective of 4 types of health care insurers in the United
      States: health maintenance organizations (HMOs), indemnity plans, preferred
      provider organizations (PPOs), and point-of-service (POS) plans. RESULTS: Median
      QATTP with graded weights was 9.7 months for anastrozole, compared with 4.6
      months for tamoxifen (P = 0.003). A resultant reduction in health care resource
      utilization was observed, particularly the requirements for hospitalization,
      outpatient visits, and chemotherapy, but the statistical significance of this
      observation was not assessed. Incremental cost savings per patient before and
      after disease progression were observed with anastrozole compared with tamoxifen
      (9064 dollars for HMO, 9678 dollars for indemnity plan, 14,273 dollars for PPO,
      and 12,715 dollars for POS; all P < 0.01). CONCLUSIONS: In the US managed care
      setting, anastrozole produced a higher QATTP and incurred lower treatment costs
      than tamoxifen in a population of postmenopausal women with predominantly hormone
      receptor-positive advanced breast cancer. Therefore, anastrozole was more cost
      effective than tamoxifen as first-line endocrine therapy in the population
      studied.

PMID- 14693320
TI  - The association between the length of the QT interval and mortality in the
      Cardiovascular Health Study.
AB  - PURPOSE: A long QT interval is a risk factor for arrhythmic events and sudden
      death. Whether moderate QT prolongation is associated with clinical events in
      community-dwelling elderly patients is uncertain. METHODS: We measured the QT
      interval in a population-based sample of 5888 men and women at least 65 years of
      age who were participants in the Cardiovascular Health Study. The association
      between Bazett's rate-corrected QT (QTc, in ms) and mortality during the
      subsequent 10 years was evaluated. We stratified participants by the presence or
      absence of coronary heart disease status at baseline, and adjusted for coronary
      heart disease risk factors. RESULTS: The rates of all-cause and coronary heart
      disease mortality were greater in participants with longer QTc intervals. Among
      participants without known coronary heart disease, those whose QTc interval was
      >450 ms were at increased risk of all-cause mortality (relative risk [RR] = 1.34;
      95% confidence interval [CI]: 1.07 to 1.67) and coronary heart disease mortality
      (RR = 1.6; 95% CI: 1.0 to 2.5) when compared with participants whose QTc interval
      was <410 ms. The associations were stronger among those with known coronary heart
      disease (RR for all-cause mortality = 2.3; 95% CI: 1.6 to 3.3; and RR for
      coronary heart disease mortality = 2.0; 95% CI: 1.1 to 3.7). CONCLUSIONS: The QT
      interval from the standard electrocardiograms is of value for identification of
      elderly persons at increased risk of coronary heart disease and total mortality.
      A QTc interval >450 ms should prompt clinical evaluation and possible
      interventions to reduce the risk of coronary events.

PMID- 14693321
TI  - Admission C-reactive protein levels and 30-day mortality in patients with acute
      myocardial infarction.
AB  - BACKGROUND: Elevated C-reactive protein levels are associated with an increased
      risk of subsequent cardiovascular events in patients with unstable angina.
      However, limited information is available concerning the value of C-reactive
      protein levels in patients with acute myocardial infarction. METHODS: We
      prospectively studied 448 consecutive patients (mean [+/- SD] age, 60 +/- 12
      years) with acute myocardial infarction. Serum C-reactive protein levels were
      measured within 12 to 24 hours of symptom onset, and divided into tertiles.
      Infarct size was determined by echocardiographic examination that was performed
      on day 2 or 3. Patients were followed for 30 days for mortality and subsequent
      cardiac events. RESULTS: At 30 days, 4 deaths (3%) occurred in patients in the
      lowest C-reactive protein tertile, 15 (10%) in patients in the middle tertile (P
      = 0.02 vs. the lowest tertile), and 33 (22%) in patients in the highest tertile
      (P <0.001 vs. the lowest tertile). In a multivariate analysis, C-reactive protein
      in the upper tertile was associated with 30-day mortality (relative risk = 3.0;
      95% confidence interval [CI]: 1.3 to 7.2; P = 0.01) and the development of heart
      failure (odds ratio = 2.6; 95% CI: 1.5 to 4.6; P = 0.0006). C-reactive protein
      levels were not associated with the development of postinfarction angina,
      recurrent myocardial infarction, or the need for revascularization. CONCLUSION:
      Plasma C-reactive protein level obtained within 12 to 24 hours of symptom onset
      is an independent marker of 30-day mortality and the development of heart failure
      in patients with acute myocardial infarction. These findings suggest that C
      reactive protein levels may be related to inflammatory processes associated with
      infarct expansion and postinfarction ventricular remodeling.

PMID- 14693322
TI  - Reduction of C-reactive protein levels through use of a multivitamin.
AB  - PURPOSE: Elevated C-reactive protein levels are associated with the risk of
      cardiovascular disease and diabetes. We examined whether multivitamins reduce C
      reactive protein levels. METHODS: We performed a post hoc subgroup analysis of a
      6-month, randomized, double-blind, placebo-controlled trial. Patients (n = 87;
      mean age, 53 years) for whom frozen plasma samples were available; who did not
      have an inflammatory condition at baseline; and who were not hospitalized, taking
      antibiotics, smoking, or starting statin therapy during the study were included.
      C-reactive protein and plasma vitamin levels were measured at baseline and 6
      months. RESULTS: At 6 months, C-reactive protein levels were significantly lower
      in the multivitamin group than in the placebo group (between-group difference = 
      0.91 mg/L; 95% confidence interval: -1.52 to -0.30; P= 0.005). The reduction in C
      reactive protein levels was most evident in patients who had elevated levels (>
      or =1.0 mg/L) at baseline. Of the six vitamins measured (C, E, B(6), B(12),
      folate, and beta carotene), only vitamin B(6) (baseline: r = -0.31, P= 0.003; 6
      months: r = -0.29, P= 0.006) and vitamin C (baseline: r = -0.25, P= 0.02) were
      inversely associated with C-reactive protein level. CONCLUSION: In a post hoc
      analysis of a randomized, double-blind, placebo-controlled study, multivitamin
      use was associated with lower C-reactive protein levels. Other similarly
      formulated multivitamins may yield comparable results.

PMID- 14693323
TI  - Prediction of outcome after percutaneous coronary intervention for the acute
      coronary syndrome.
AB  - BACKGROUND: The seven-component Thrombolysis In Myocardial Infarction (TIMI)
      score has been used to risk stratify, and to guide the medical management of,
      patients with unstable angina or non-ST-elevation myocardial infarction. We
      assessed the usefulness of the risk score in predicting in-hospital and 30-day
      outcomes in such patients who were undergoing percutaneous coronary intervention.
      METHODS: Using the TIMI score, 2501 patients with unstable angina or non-ST
      elevation myocardial infarction were divided into low-risk (zero to two risk
      factors; n = 974), intermediate-risk (three to four risk factors; n = 1339), and
      high-risk (five to seven risk factors; n = 188) groups, and outcomes were
      compared. RESULTS: Angiographic/clinical success and the rate of minor procedural
      events were similar among the three groups. A higher TIMI risk score was
      associated with more cardiac comorbid conditions and more complicated
      angiographic lesions: longer lesions (P = 0.0009), more thrombotic lesions (P =
      0.03), more multivessel disease (P <0.0001), and more American College of
      Cardiology/American Heart Association type B2/C lesions (P = 0.05). Although the
      risk score did not predict interventional technical success or intraprocedural
      complications, a high score was associated with prolonged hospital stay, higher
      postprocedural peak troponin levels, and 30-day major adverse cardiac events.
      Stepwise logistic regression showed that in conjunction with lesion length and
      patient sex, a high score was an independent predictor of 30-day major adverse
      cardiac events (odds ratio = 2.3; 95% confidence interval: 1.1 to 4.1; C
      statistic = 0.62). CONCLUSION: Although a higher TIMI risk score in patients with
      unstable angina or non-ST-elevation myocardial infarction who were undergoing
      percutaneous coronary intervention correlated with adverse clinical outcome, the
      score alone cannot be used to guide diagnostic or therapeutic strategies.

PMID- 14693324
TI  - Determinants of selective cyclooxygenase-2 inhibitor prescribing: are patient or
      physician characteristics more important?
AB  - BACKGROUND: Little is known about which factors influence the widespread use of
      selective cyclooxygenase (COX)-2 inhibitors. We examined the relative effects of
      patient risk factors for gastrointestinal toxicity, other patient
      characteristics, and physician prescribing preferences on the decision to
      prescribe a selective COX-2 inhibitor. METHODS: We retrospectively studied a
      cohort of 28,190 Medicare beneficiaries who were continuously enrolled in a
      large, state-run pharmacy benefits program that reimbursed for selective COX-2
      inhibitors and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) without
      restrictions. Half of the study sample filled a prescription for a selective COX
      2 inhibitor and the other half for a nonselective NSAID. Multivariable logistic
      regression models were developed to predict COX-2 inhibitor use. RESULTS:
      Seventeen percent of patients using a COX-2 inhibitor had no identifiable risk
      factor for NSAID-associated gastrointestinal toxicity, compared with 23% of those
      using a nonselective NSAID. Established risk factors (age > or =75 years, history
      of gastrointestinal hemorrhage or peptic ulcer disease, or concomitant warfarin
      or oral glucocorticoid use) were all significant predictors of COX-2 inhibitor
      use, but a multivariable model including only these risk factors discriminated
      poorly between the two patient groups (C statistic = 0.55). Adding other patient
      clinical and demographic characteristics to the model somewhat improved this
      association (C statistic = 0.66); however, when physician prescribing preference
      was included, the model had excellent ability to discriminate between the two
      treatment groups (C statistic = 0.83). CONCLUSION: Established risk factors for
      NSAID-associated gastrointestinal toxicity were poor predictors of who was
      prescribed a selective COX-2 inhibitor; in contrast, physician prescribing
      preference was an important determinant.

PMID- 14693325
TI  - Hypercoagulability in sickle cell disease: a curious paradox.
AB  - There is evidence of activation of both blood coagulation and platelets in sickle
      cell disease. For example, plasma samples obtained in the steady state and during
      painful crisis demonstrate high levels of thrombin generation, depletion of
      anticoagulant proteins, and abnormal activation of the fibrinolytic system.
      Similarly, exposure of surface markers such as CD62P and CD40L, along with
      increased circulating levels of thrombospondin, signal platelet activation. In
      addition to its effects on the cleavage of fibrinogen and its ability to activate
      platelets, the increase in circulating thrombin levels, with its wide-ranging
      effects on endothelial cells and blood vessels, may be important in the
      pathophysiology of sickle cell disease. Therefore, treatments that could decrease
      thrombin generation or platelet activation may be beneficial in both the
      treatment of sickle cell disease and the prevention of complications that
      characterize this genetic disorder. This review discusses hypercoagulability in
      the various forms of sickle cell disease, including homozygous sickle cell
      anemia, hemoglobin SC disease, hemoglobin SD disease, and sickle cell-beta
      thalassemia.

PMID- 14693326
TI  - Cases from the Osler Medical Service at Johns Hopkins University. Zieve syndrome.

PMID- 14693327
TI  - QT interval: metric for cardiac prognosis?

PMID- 14693328
TI  - Should C-reactive protein be measured routinely during acute myocardial
      infarction?

PMID- 14693329
TI  - Overlapping publications.

PMID- 14693331
TI  - Septicemia caused by retained pacemaker lead tip.

PMID- 14693332
TI  - Perioperative reduction of the warfarin dose.

PMID- 14693333
TI  - Systemic amyloidosis with pleural involvement.

PMID- 14693334
TI  - An anterior chest wall mass.

PMID- 14693335
TI  - Centers, institutes, and the future of clinical departments: Part II.

PMID- 14693336
TI  - Gynecologic Oncology specialty: progressing towards recognition in Europe.

PMID- 14693337
TI  - Microinvasive squamous cell cervical carcinoma.
AB  - Several histologic tumor-related features are the key factors for further
      treatment planning in microinvasive cervical cancer (MIC) after conization. To
      better define the indications for conservative treatment of MIC we conducted a
      literature review for prognostic factors for MIC and we carried out a prospective
      observational study evaluating most important pathologic factors and the
      relationships between tumor and edges of the cone and incidence of recurrences.
      In our experience seven recurrences were observed. Two distinct groups of
      patients were identified with a clearance lower or higher of 10 and 8 mm for
      apical and lateral margin respectively. Depth of infiltration and even lymph
      vascular involvement have been confirmed as the most important histologic
      parameters to be evaluated. Apical and lateral clearance of the tumor are
      significantly correlated with the recurrence rate. If an adequate lateral border
      of healthy tissue is present on the specimen, conization may be considered as
      definitive treatment of MIC.

PMID- 14693338
TI  - Modulation of surgery in early invasive cervical cancer.
AB  - In modern oncology increasing attention is given to patient quality of life
      issues. Reduction of morbidity and preservation of reproductive organs are
      aspects of major concern for surgeons treating women affected by gynecologic
      tumors. To achieve these goals both improvements of surgical technique and peri
      operative management, but mainly a better individualization of therapy are
      needed. This requires: (1) advanced knowledge of the natural history of disease,
      (2) accurate pathological evaluation, (3) innovative diagnostic tools. In the
      last decades remarkable progresses have been made in these fields making
      modulation of surgery a concrete option in the treatment of early invasive
      cervical cancer. Currently, tumor volume measurements by step serial section of
      cone specimen (stage IA(2) and small volume IB(1)), sentinel nodal group
      lymphadenectomy and sentinel node biopsy (stage IB(1)) represent the best
      techniques available for assessing the risk of extracervical spread of disease
      allowing tailoring of patient management to optimize the patients outcome and
      quality of life.

PMID- 14693339
TI  - Nerve sparing radical hysterectomy: latest developments and historical
      perspective.
AB  - Autonomic nerve damage during surgery is thought to play a crucial role in the
      aetiology of bladder dysfunction, sexual dysfunction and colorectal motility
      disorders which are seen in patients after radical hysterectomy. In order to
      prevent these complications, Japanese gynaecologists introduced a surgical
      technique with preservation of the pelvic autonomic nerves in the 1960s. In the
      1980s the first English paper was published. Since then several surgical
      approaches have been described, i.e. liposuction, electrical stimulation to
      locate nerves intra-operatively and laparoscopically assisted techniques.
      Recently, more attention is being paid to the importance of sparing the
      sympathetic hypogastric nerve. All authors report results on small cohorts of
      patients. The incidence of urinary dysfunction seems very low after nerve
      sparing. Sparing the autonomic nerves during radical hysterectomy seems feasible
      and safe in both Japanese and Western patients. Literature review does not
      provide strong clues for a compromised radicality and cure due to nerve sparing.
      Future larger clinical trials will have to decide whether the technique of nerve
      sparing radical hysterectomy could be implemented as a standard treatment for
      cervical cancer patients.

PMID- 14693340
TI  - Continent urinary diversion and low colorectal anastomosis after pelvic
      exenteration. Quality of life and complication risk.
AB  - INTRODUCTION: Pelvic exenteration is one of the most destructive gynecologic
      operations performed on an elective basis, with consequent detrimental effects on
      the quality of life. The use of reconstructive surgery has significantly improved
      the quality of life of women undergoing this type of procedure. In this paper we
      review our experience with continent urinary diversion (Miami Pouch) and low
      colorectal anastomosis at the Division of Gynecologic Oncology of the University
      of Miami. METHODS: Patients who underwent creation of the continent urinary
      diversion Miami Pouch from 1988 to 1997 and supralevator pelvic exenteration with
      low colorectal resection and primary anastomosis from 1990 to 1997 have been
      included in this study. Management of complications, with particular emphasis on
      the conservative treatment, has been reviewed in detail for each patient. Open
      surgery and conservative treatment have been compared. Analysis of complications
      in irradiated and nonirradiated patients was performed. RESULTS: 77 patients who
      underwent creation of the Miami Pouch entered this study. Forty patients
      underwent total pelvic exenteration, and 37 patients underwent posterior
      exenteration. The most common urinary complications were ureteral
      stricture/obstruction (22.1%), difficult catheterisation (19.5%) and
      pyelonephritis (16.9%). Conservative management strategies were successfully used
      in 80% of the complications. Analysis of breakdown and fistula formation after
      low colorectal anastomosis was performed on 77 patients. Thirty-five percent of
      the irradiated patients developed anastomotic breakdown or fistulas, while the
      occurrence of this type of complications was only 7.5% in the nonirradiated
      group. CONCLUSIONS: Reconstructive procedures after pelvic exenteration present a
      significant risk of complications, especially in irradiated patients. Most of the
      complications related to the creation of continent urinary diversion can safely
      be treated conservatively. Low colorectal anastomosis carries an acceptable risk
      of complications in nonirradiated patients, but the risk in irradiated patients
      is very high, therefore, detailed patient selection and extensive counselling in
      these groups of patients is mandatory.

PMID- 14693341
TI  - Vesical dysfunctions after radical hysterectomy for cervical cancer: a critical
      review.
AB  - Functional disorders of the lower urinary tract are the most common long-term
      complications following radical surgery for cancer of the uterine cervix (8-80%).
      These disturbances were associated to the partial interruption of the autonomic
      fibers innervating the bladder during the resection of anterior, lateral and
      posterior parametrium and vaginal cuff. The pathophysiology of these changes is
      actually debated. The nature of the surgical damage appears to be a
      decentralization rather than a complete denervation and bladder dysfunctions may
      be either the unmasking of intrinsic detrusor activity, characterized by a loss
      of beta-adrenergic innervation and a consequent alfa-adrenergic hyperinnervation
      or the influence of remaining sympathetic innervation. No data on long-term
      bladder function in patients who underwent class 4 radical hysterectomy have been
      reported. In our experience on long-term vesical function in 38 patients with
      locally advanced cervical cancer treated with neoadjuvant chemotherapy and 4
      Piver type radical hysterectomy, urinary symptoms were reported in 11 patients
      (29%), while a normal urodynamic finding was recorded in only nine patients
      (24%). The most common bladder dysfunction was the storage dysfunction (47%). The
      voiding dysfunction was present in one patient (3%) and stress urinary
      incontinence in 20 patients (53%). The parametrial and vaginal resections were
      compared among the urodynamic diagnosis The size of lateral parametria measured
      on the giant sections did not differ among the groups of urodynamic diagnosis,
      while the length of vagina removed was significantly longer in patients with
      detrusor dysfunctions (storage and voiding dysfunctions) than in patients with
      normal diagnosis or genuine stress incontinence.

PMID- 14693342
TI  - Guidelines of how to manage vesicovaginal fistula.
AB  - Vesicovaginal fistulas are among the most distressing complications of
      gynecologic and obstetric procedures. The risk of developing vesicovaginal
      fistula is more than 1% after radical surgery and radiotherapy for gynecologic
      malignancies. Management of these fistulas has been better defined and
      standardized over the last decade. We describe in this paper the success rate
      reported in the literature by treatment modality and the guidelines used at our
      teaching hospitals, University of Rome Campus Biomedico and University of Miami
      School of Medicine. In general, our preferred approach is a trans-vaginal repair.
      To the performance of the surgical treatment, we recommend a minimum of a 4-6
      week's wait from the onset of the fistula. The vaginal repair techniques can be
      categorized as to those that are modifications of the Latzko procedure or a
      layered closure with or without a Martius flap. The most frequently used
      abdominal approaches are the bivalve technique or the fistula excision. Radiated
      fistulas usually require a more individualized management and complex surgical
      procedures. The rate of successful fistula repair reported in the literature
      varies between 70 and 100% in non-radiated patients, with similar results when a
      vaginal or abdominal approach is performed, the mean success rates being 91 and
      97%, respectively. Fistulas in radiated patients are less frequently repaired and
      the success rate varies between 40 and 100%. In this setting many institutions
      prefer to perform a urinary diversion. In conclusion, the vaginal approach of
      vesicovaginal fistulas repair should be the preferred one. Transvaginal repairs
      achieve comparable success rates, while minimizing operative complications,
      hospital stay, blood loss, and post surgical pain. We recommend waiting at least
      4-6 weeks prior to attempting repair of a vesicovaginal fistula. It is acceptable
      to repeat the repair through a vaginal approach even after a first vaginal
      approach failure. In the more individualized management of fistulas associated
      with radiation, the vaginal approach should still be considered.

PMID- 14693343
TI  - Laparoscopic assessment of the sentinel lymph nodes in early cervical cancer.
      Technique--preliminary results and future developments.
AB  - Laparoscopic assessment of the sentinel node (SN) in early stage cervical cancer
      is both feasible and safe. The technique is described. The data concerning the 70
      first assessed patients are reported. Failure in identification of the SN
      occurred in 14 of the 139 attempted dissections. One only SN was detected in 121
      dissections and two SN in four dissections. A systematic pelvic lymphadenectomy
      was carried out after removal of the SN. A metastatic involvement of the SN was
      put in evidence in 19 of the 129 retrieved SN. The other regional lymph nodes
      were. The data concerning the 70 first assessed patients are reported. Failure in
      identification of the SN occurred in 14 of the 139 attempted dissections. One
      only SN was detected in 121 dissections and two SN in four dissections. A
      systematic pelvic lymphadenectomy was carried out after removal of the SN. A
      metastatic involvement of the SN was put in evidence in 19 of the 129 retrieved
      SN. The other regional lymph nodes were involved in 13 cases and not involved in
      six cases. In the 110 cases where the SN was not involved all the other regional
      nodes were free from metastasis. At the condition larger series confirm the
      preliminary results the laparoscopic retrieval of the SN could change the
      strategy to be used in the management of early stage cervical cancer: no
      systematic lymphadenectomy-radiotherapy for the SN+ patients--vaginal radical
      hysterectomy for the SN- patients. Another condition should be the SN is
      submitted to superstaging using immunochemical staining and/or molecular biology.

PMID- 14693344
TI  - Bowel preparation for gynecological surgery.
AB  - Bowel preparation is an established practice before abdominal surgery. Most
      surgeons would use both antibiotic prophylaxis and mechanical bowel preparation
      (MBP) before bowel surgery. In the literature, however, there is no evidence to
      support the use of MBP before elective colorectal surgery. Some randomized
      studies and a meta-analysis report a significantly higher incidence of wound
      infection in patients receiving MBP versus no bowel preparation. As to
      gynecological surgery, data are scanty, and there is a single randomized study
      reporting no advantage of MBP over no bowel preparation. Based on these
      evidences, the routine use of MBP should be reconsidered both in general and
      gynecological surgery.

PMID- 14693345
TI  - The role of the French-Italian glossary of complications in the outcome
      evaluation of cervical cancer treatment: an Italian multicentric study.
AB  - The optimal treatment for cervical cancer is still a controversial matter: in the
      last two decades a lot of different modalities combining surgery, radiotherapy
      (RT) and chemotherapy (CHT) have been suggested and analysed in clinical trials.
      Nevertheless, analysis of treatment in cancer patients should be directed not
      only to survival, but also to the cost of complications and quality of life. In
      June 1988, a French-Italian co-operative group set up a glossary in which the
      complications of the treatment of cervical cancer are described and ranked.
      Nowadays, this is the only international system based upon an accurate
      description of symptoms and signs of complications following multidisciplinary
      treatment. The glossary was based on our previous experience in treating patients
      by surgery alone, RT or their combinations. Recently multimodality treatment
      includes also CHT. The aim of the present study was to verify whether the
      glossary is still a useful clinical instrument in outcome evaluation of cervical
      cancer treatment. MATERIALS AND METHODS: The analysis has been done on a
      retrospective consecutive series of 579 patients affected by cervical cancer,
      treated in five Italian institutions. A minimum of 12 months follow up was
      required. All medical records of the patients enrolled, were examined by two
      independent reviewers in order to classify the complications according to the
      glossary. RESULTS: Out of 579 patients 319 (55.1%) were free of complications and
      260 (44.9%) experienced at least one complication. We found 436 complications.
      The distribution by Grade was: G1 58.9%, G2 27.5%, G3 13.5%. We had no fatal
      complication (G4). The glossary included all observed complications, except for
      pulmonary fibrosis. CONCLUSION: The glossary is still a useful instrument in
      evaluating the outcome of cervical cancer treatment, whatever the therapy, and
      should be considered in quality of life assessment.

PMID- 14693346
TI  - New drugs in the treatment of recurrent or metastatic cervical cancer.
AB  - Cervical cancer is the second major cause of death in women. In locally-advanced
      or refractory cervical cancer, cisplatin-based chemotherapy still represents the
      best chance of cure, although chemotherapy in these patients usually results in
      excessive toxicity and short duration of response. Newly developed chemotherapy
      agents, widely used in other cancers, have been employed as single agents and in
      combination with cisplatin in the treatment of locally advanced or recurrent
      cervical cancer. Several phase II-studies have been performed in order to assess
      the effectiveness of gemcitabine, paclitaxel, vinorelbine and camptothecines in
      cervical cancer. When used as single agents, these compounds have an overall
      response rate (ORR) of 8-25%. Cisplatin-combined regimens may offer improved
      efficacy, with a ORR between 41 and 60%. Toxicity remains the more limiting
      factor in the treatment of irradiated or pretreated patients. New targets must be
      identified for innovative therapeutic approaches that could improve the response
      rate and survival of cervical cancer patients.

PMID- 14693347
TI  - No association between season of birth of patients with schizophrenia and risk of
      schizophrenia among their siblings.
AB  - Previous studies on the relationship between the season of birth of patients with
      schizophrenia and the risk of schizophrenia among their siblings have yielded
      contradictory results. We investigated whether proband's month of birth affects
      siblings' risk of developing schizophrenia. We used the Finnish Hospital
      Discharge Register to identify all patients born in Finland from 1950 to 1976 who
      had been hospitalized because of schizophrenia at least once between 1969 and
      1995. Their siblings were identified from the National Population Register, and
      data on siblings were linked to the Hospital Discharge Register to obtain
      information on any hospitalizations. We used logistic regression to investigate a
      sibling's probability of developing schizophrenia, defining the proband initially
      as the first sibling in calendar time to develop schizophrenia, then as the
      affected sibling with lowest onset age. Within-family dependence was taken into
      account by using robust standard error estimates. Neither models found any
      association between proband's month of birth and siblings' odds of developing
      schizophrenia. Our results support those previous studies that found no
      association between proband's month of birth and family history of schizophrenia,
      and suggest that the winter-spring excess of births among patients with
      schizophrenia is not caused by any genetic or environmental risk factor that
      operates independently of other risk factors.

PMID- 14693348
TI  - Schizophrenia and season of birth: relationship to geomagnetic storms.
AB  - An excess pattern of winter and spring birth, of those later diagnosed as
      schizophrenic, has been clearly identified in most Northern Hemisphere samples
      with none or lesser variation in Equatorial or Southern Hemisphere samples.
      Pregnancy and birth complications, seasonal variations in light, weather,
      temperature, nutrition, toxins, body chemistry and gene expression have all been
      hypothesized as possible causes. In this study, the hypothesis was tested that
      seasonal variation in the geomagnetic field of the earth primarily as a result of
      geomagnetic storms (GMS) at crucial periods in intrauterine brain development,
      during months 2 to 7 of gestation could affect the later rate of development of
      schizophrenia. The biological plausibility of this hypothesis is also briefly
      reviewed. A sample of eight representative published studies of schizophrenic
      monthly birth variation were compared with averaged geomagnetic disturbance using
      two global indices (AA*) and (aa). Three samples showed a significant negative
      correlation to both geomagnetic indices, a further three a significant negative
      correlation to one of the geomagnetic indices, one showed no significant
      correlation to either index and one showed a significant positive correlation to
      one index. It is suggested that these findings are all consistent with the
      hypothesis and that geomagnetic disturbance or factors associated with this
      disturbance should be further investigated in birth seasonality studies.

PMID- 14693349
TI  - Rheumatoid arthritis and schizophrenia: a negative association at a dimensional
      level.
AB  - There is wide evidence for a decreased risk of rheumatoid arthritis in patients
      with schizophrenia. Nevertheless, very few studies have looked at the risk of
      schizophrenia in a group of patients with rheumatoid arthritis. We prospectively
      investigated, with the SCL-90R, 220 consecutive outpatients with rheumatoid
      arthritis and 196 consecutive outpatients with various medical conditions, half
      of them suffering from psoriatic arthritis (a medical condition close to
      rheumatoid arthritis). The SCL-90R appears to be a valuable tool to distinguish
      patients with schizophrenia from the outpatients of our sample, the former having
      more "paranoid ideation" (p = 0.004) and more "psychoticism" (p < 0.001) than the
      latter. The "paranoid ideation" dimension was significantly lower (25% decrease)
      in the sample of patients with rheumatoid arthritis compared to the combined
      control group (p = 0.005), ratings under the median value being more frequent in
      the former group (p = 0.025). Confounding factors might not explain this
      difference according to the regression logistic analysis performed. As patients
      with rheumatoid arthritis have a lower score of paranoid ideation than controls
      in our sample, even after controlling for age, gender and severity of the
      disease, these data represent further evidence for a decreased risk of
      schizophrenia in individuals with rheumatoid arthritis.

PMID- 14693350
TI  - Treatment of rats with antipsychotic drugs: lack of an effect on brain N-acetyl
      aspartate levels.
AB  - BACKGROUND: Proton magnetic resonance spectroscopy (1H-MRS) studies of
      schizophrenia suggest an effect of the disease or of antipsychotic medications on
      brain N-acetyl aspartate (NAA), a marker of neuronal viability. We studied in the
      rat the effect of antipsychotic drugs on NAA in several brain regions where NAA
      reductions have been reported in chronically medicated patients with
      schizophrenia. METHODS: Three groups of nine rats each were treated with
      haloperidol (6 mg/kg/day), clozapine (70 mg/kg/day) and vehicle for 6 weeks and
      were sacrificed. Concentrations of NAA were determined by high-performance liquid
      chromatography (HPLC) from the following brain regions: cortex, striatum,
      thalamus, hippocampus and cerebellum. RESULTS: Mixed-factorial ANOVA of NAA
      concentrations revealed no significant effect of drug group [F(2, 24) = 0.034; p
      = 0.966] or a group by brain region interaction [F(8, 44) = 0.841; p = 0.572].
      There was a significant main effect of region [F(4, 21) = 6.104; p = 0.002] with
      higher NAA in the cortex. CONCLUSIONS: These results are consistent with the only
      other study of the effect of typical and atypical antipsychotic drugs on NAA in
      the rat brain. The well-documented lower NAA in chronically treated schizophrenia
      patients is probably not a simple effect of antipsychotic medications.

PMID- 14693351
TI  - Gender and the use of neuroleptics in schizophrenia.
AB  - INTRODUCTION: The oestrogen hypothesis proposes that the lower need for
      neuroleptic drugs in female schizophrenia patients is caused by the
      antidopaminergic effect of oestrogens, and that when oestrogen production
      decreases at menopause, the need for neuroleptic drugs increases in female
      schizophrenia patients. SUBJECTS AND METHOD: The oestrogen hypothesis was tested
      in a sample of 4338 schizophrenia patients (DSM III R), who were discharged from
      hospital and followed up for 3 years. Prescribed daily doses of neuroleptics
      (DDN) were recorded and converted to chlorpromazine equivalents. RESULTS: Males
      had higher DDN than females. When the age at first admission (AFA) was
      controlled, DDNs were higher in males than in females in all age groups. In
      addition to AFA, DDNs were associated with duration of illness (DUI), education,
      smoking and clinical status as well as with concurrently prescribed
      antidepressants, anti-manics, sedatives and hypnotics, but these factors did not
      explain the gender differences in DDN. CONCLUSIONS: The results did not support
      the original oestrogen hypothesis. It is proposed that testosterone secretion may
      explain why male schizophrenia patients are prescribed higher DDNs than female
      patients. Ageing processes in the central nervous system (CNS) may explain why
      DDNs decrease after middle age in both genders.

PMID- 14693352
TI  - Obesity as a risk factor for antipsychotic noncompliance.
AB  - OBJECTIVE: Weight gain is a common side effect of antipsychotic medications and
      is of particular concern with most of the newer "atypical" antipsychotics. It is,
      therefore, increasingly important to understand the impact of obesity and
      perceived weight problems on compliance with these medications. METHODS: A survey
      of treatment and health issues was mailed to local chapters of the National
      Alliance for the Mentally Ill (NAMI) and National Mental Health Association
      (NMHA), who distributed them to people with schizophrenia. Noncompliance was
      defined as a self-report of missing any antipsychotic medication in the previous
      month. The primary independent variables were (1) body mass index (BMI; weight
      [kg]/height [m2])-categorized as normal (< 25, n = 73), overweight (25-30, n =
      104), or obese (> 30, n = 100)-and (2) subjective distress over weight gain.
      Other independent variables included demographics, medication attitudes, and
      treatment satisfaction. RESULT: BMI status and subjective distress from weight
      gain were predictors of noncompliance. Obese individuals were more than twice as
      likely as those with a normal BMI to report missing their medication (OR = 2.5;
      CI 1.1-5.5). A comprehensive model suggested that the primary mediator of
      noncompliance was distress over weight gain. CONCLUSIONS: There appears to be a
      significant, positive association between obesity and subjective distress from
      weight gain and medication noncompliance, even when accounting for other possible
      confounding factors.

PMID- 14693354
TI  - Preferences among antipsychotic medications given particular clinical scenarios.

PMID- 14693353
TI  - Further validation of the Client Assessment of Strengths Interests and Goals.
AB  - The Client Assessment of Strengths Interests and Goals (CASIG), a measure that
      assesses the treatment outcomes of individuals with serious and persistent mental
      illness, has previously shown adequate psychometric properties with an American
      sample. Since it assesses quite specific skills and needs, it is necessary to
      assess its cultural relevance and psychometric characteristics before using it in
      a different country. Hence, the purposes of this study were to (1) adapt CASIG to
      the culture of a Canadian setting and translate its items and directions into
      French, (2) determine the psychometric characteristics of the adapted English and
      French versions of CASIG, and (3) identify its latent constructs via an
      exploratory factor analysis. The CASIG self-report (CASIG-SR) measure was
      administered to 224 consumers living in the community, and the CASIG informant
      (CASIG-I) measure to 31 clinicians answering for 172 consumers. The participating
      consumers also completed the Behavior and Symptom Identification Scale-32 (BASIS
      32), the Short Form Health Survey-36 (SF-36), and the Camberwell Assessment of
      Needs (CAN). The informants also completed the clinician version of the CAN. The
      CASIG-SR and the CASIG-I had adequate internal consistency, test-retest, and
      interrater reliabilities. Correlations of the consumers' and informants' results
      with the BASIS-32, SF-36, and CAN provided evidence of convergent and
      discriminant validity, as did contrasts between higher and lower functioning
      community consumers. The factor analysis also supports the construct validity of
      the assessment. The results confirm the psychometric adequacy of the adapted and
      translated CASIG in Canada.

PMID- 14693355
TI  - A low-cost, telephone intervention to enhance schizophrenia treatment: a
      demonstration study.

PMID- 14693356
TI  - Bone mineral density and prolactin associations in patients with chronic
      schizophrenia.

PMID- 14693357
TI  - Schizophrenia in the offspring of antenatally depressed mothers: a 31-year follow
      up of the Northern Finland 1966 Birth Cohort.

PMID- 14693359
TI  - Logical reasoning deficits in schizophrenia.

PMID- 14693358
TI  - Air pollution from traffic and schizophrenia risk.

PMID- 14693360
TI  - Task-related coupling from high- to low-frequency signals among visual cortical
      areas in human subdural recordings.
AB  - Cortical cooperativity during cognitive demands includes high- and low-frequency
      activities, which raises the question whether there are interdependencies between
      fast and slow processes and how they are reflected in electrical brain signals.
      We had the opportunity to record signals intracranially from occipital visual
      areas in an epileptic patient and quantified inter-areal signal coupling while
      the patient performed a visual delayed-match-to-sample task. We computed
      coherence, phase consistency and amplitude envelope correlation and we also
      determined inter-frequency coupling through correlation between low-frequency
      signal components and amplitude envelopes of high-frequency components. There was
      a pronounced task-related increase of correlation between gamma-band (28-70 Hz)
      signal envelopes from a superior (occipital) and low-frequency (0-3.5 Hz) signals
      from an inferior (occipital) visual area, lasting for approximately 1 s and
      possibly reflecting a short-term memory encoding process. The correlational delay
      between envelopes and low-frequency components was 40 ms. In contrast, coherence,
      phase consistency and envelope correlation showed event-, but no task-related
      changes of intra-areal and no changes of inter-areal coupling. Our data suggest a
      specific effect of gamma-activity in the superior onto low-frequency activity in
      the inferior area. We argue that temporal dispersion of conduction delays might
      prevent coherent transmission of high-frequency signals and thus account for the
      absence of gamma-coherence. As such dispersion is a general property of long
      range projections, envelope-to-signal correlation possibly reflects a general
      neuronal mechanism. Hence, our method provides a powerful tool for detecting such
      inter-areal interactions not visible with conventional linear coupling measures.

PMID- 14693361
TI  - Comparative EEG activation to skin pain and muscle pain induced by capsaicin
      injection.
AB  - Skin pain differs from muscle pain in quality and affective dimension, but it is
      unknown how the brain processes the nociceptive inputs from skin and muscle
      differently. To delineate the differential effects of nociceptive inputs from
      skin and muscle, the EEG topography and power spectra were analysed on the basis
      of two databases acquired from two separate studies regarding skin (Neurosci.
      Lett. 305 (2001b) 49) and muscle pain (Exp. Brain Res. 141 (2001c) 195). The same
      experimental protocol was applied to the same subject-group in the two separate
      experiments. In the two independent experiments, skin pain and muscle pain were,
      respectively, induced by intracutaneous and intramuscular injection of capsaicin
      in the left forearm. Visual analogue scale (VAS) and EEG data acquired before,
      during the vehicle and capsaicin injections were quantitatively compared. The
      results showed that the VAS profiles for skin and muscle pain are highly similar
      in spite of distinct qualities perceived. Skin pain produced a similar but not
      identical EEG topographic pattern as muscle evoked. Muscle pain induced a
      significant increase of beta-2 activity in the extensive frontal, parietal and
      occipital areas compared to skin pain. No difference was found between the
      vehicle-induced non-painful sensations in skin and muscle. These results
      implicate that the nociceptive inputs from muscle and skin are processed
      differently in the similar neural matrix of the brain.

PMID- 14693362
TI  - Can premorbid episodes of diminished vagal tone be detected via histological
      markers in patients with PTSD?
AB  - While laboratory methods for estimating genetic susceptibility for adult
      psychopathology have received much recent attention, laboratory methods for
      objectively estimating a person's early autonomic nervous system perturbations
      have been under-researched. Research on heart rate variability suggests that
      early life episodes of diminished vagal tone may predict poor stress resilience
      in adults. This article will detail a research method for retrospectively
      estimating in adults the chronology of diminished vagal tone episodes experienced
      prior to age 10. This method makes use of the developing enamel matrix, one of
      very few tissues that cannot recover after being stressed.

PMID- 14693363
TI  - The development of P50 suppression in the auditory event-related potential.
AB  - The development of P50 suppression in the auditory event-related potential was
      examined in 32 participants aged 7-13 years and the relation of P50 suppression
      to individual differences in social withdrawal was investigated. Auditory click
      pairs were presented binaurally and the amplitude of the P50 component was
      measured for the two clicks. Across the whole sample, P50 amplitude to the second
      click was significantly smaller than P50 amplitude to the first click, although
      around one third of participants showed augmentation of the P50 to the second
      click. For the children who showed P50 suppression, the magnitude of P50
      suppression increased with age and reached adult levels in the oldest
      participants. P50 suppression did not vary with the extent of social withdrawal
      behaviors.

PMID- 14693364
TI  - Autonomic specificity of discrete emotion and dimensions of affective space: a
      multivariate approach.
AB  - The present study addressed autonomic nervous system (ANS) patterning during
      experimentally manipulated emotion. Film clips previously shown to induce
      amusement, anger, contentment, disgust, fear and sadness, in addition to a
      neutral control film, were presented to 34 college-aged subjects while skin
      conductance, blood pressure and the electrocardiogram (ECG) were recorded, as was
      self-reported affect. Both mean of and mean successive difference of heart period
      were derived from the ECG. Pattern classification analyses revealed emotion
      specific autonomic patterning for all emotion conditions except disgust; all
      emotion conditions exhibited significant patterning using self-report.
      Discriminant function analysis was used to describe the location of discrete
      emotions within dimensional affective space using both self-report and ANS
      variables. Findings suggest that the dimensions of valence and activation portray
      the structure of self-reported emotion, but that valence is more accurately
      described as approach-withdrawal when applied to autonomic responses during
      discrete emotions. The findings provide further support for the existence of
      emotion-specific ANS activity, and are consistent with a hybrid discrete
      dimensional model of affective space.

PMID- 14693366
TI  - Assessing the effect of pain on demands for attentional resources using ERPs.
AB  - Event-related potentials were used as an adjunct to behavioral and self-report
      measures to examine the impact of pain in a short-term memory-scanning task. P3
      amplitude was reduced and a frontal slow wave was increased during pain
      regardless of the number of items in memory. Results are discussed in terms of
      pain affecting an attention-switch mechanism.

PMID- 14693367
TI  - Ets ternary complex transcription factors.
AB  - The three ternary complex factors (TCFs) Elk-1, Net and Sap-1 form a subfamily of
      the E twenty-six (Ets) domain transcription factors. Their characteristic
      property is the ability to form a ternary nucleoprotein complex with the serum
      response factor (SRF) over the serum response element (SRE) of the c-fos
      promoter. The molecular mechanisms that underlie the function and regulation of
      these factors have been extensively studied and the TCFs are a paradigm for the
      study of transcriptional regulation in response to extracellular signalling
      through the mitogen-activated protein (MAP) kinase pathway. As final effectors of
      multiple signalling pathways and components of protein complexes on immediate
      early promoters, they represent key elements in the complex and dynamic
      regulation of gene expression. This review summarises the molecular, structural
      and biochemical studies that have led to the understanding of the functional
      domains of the TCFs, ternary complex formation, transcriptional regulation,
      protein partners and target genes in cell lines. Finally, the emerging studies of
      the biological roles of the TCFs in vivo will be discussed.

PMID- 14693368
TI  - Insertion-deletion biases and the evolution of genome size.
AB  - Numerous theories have been proposed to account for the pronounced differences in
      the quantity of non-coding DNA among eukaryotic genomes, but the current
      repertoire remains incomplete because the only explicit mechanisms it provides
      involve DNA gain. It has been proposed more recently that biases in spontaneous
      insertions and deletions (indels) can lead to genome shrinkage by mutational
      mechanisms alone. The present article provides the first detailed critical
      discussion of this approach, and covers three different ideas related to it: (1)
      the general notion of DNA loss by deletion bias, (2) the "DNA loss hypothesis"
      which supposes that variation in genome size can be attributed to differences in
      DNA loss rate, and (3) the "mutational equilibrium model" which attempts to
      describe the long-term evolution of genome size. The mutational equilibrium model
      is found to be problematic, and it is noted that DNA loss by small indels is too
      slow in real time to determine variation in genome size above a relatively low
      threshold. Some alternative explanations for the observed patterns are provided,
      and the critique also identifies some potential problems with the current
      dataset. These include a failure to cite a more detailed (and somewhat
      contradictory) mammalian dataset, a questionable use of arithmetic means with
      highly skewed data, and important discrepancies among the particular DNA
      sequences so far analyzed. Overall, evolutionary reductions in genome size are
      considered important, but the specific mechanism relating to small deletion bias
      is far too weak to be accepted as a primary determinant of genome size variation
      in general.

PMID- 14693369
TI  - AtCPSF73-II gene encoding an Arabidopsis homolog of CPSF 73 kDa subunit is
      critical for early embryo development.
AB  - We have identified and genetically characterized an Arabidopsis thaliana gene
      encoding a homolog of the Cleavage and Polyadenylation Specificity Factor (CPSF).
      This gene, named AtCPSF73-II, has been found to have a critical role in
      development by loss-of-function analysis using a Dissociation (Ds) insertion line
      SGT1922. The homozygous SGT1922 plants were lethal, but the heterozygous plants,
      while retaining their normal vegetative growth, displayed empty seed spaces as
      well as aborted seeds with embryos arrested at the globular stage. Genetic
      analysis indicated that the disruption of the AtCPSF73-II gene in SGT1922 plants
      caused severe reduction in genetic transmission of female gametes due to a loss
      of fertility, while the transmission of male gametes was normal. Two independent
      heterozygous lines with T-DNA insertion on the AtCPSF73-II gene also showed the
      similar phenotype. Gene expression analysis demonstrated that AtCPSF73-II was
      preferentially expressed in flowers. Protein sequence analysis revealed a group
      of AtCPSF73-II homologs with unknown function in animals, but not in yeast, which
      suggested a potential important function of this group of genes in the
      development of multicellular organisms.

PMID- 14693365
TI  - The role of brain oscillations as functional correlates of cognitive systems: a
      study of frontal inhibitory control in alcoholism.
AB  - Event-related oscillations play a key role in understanding the brain dynamics
      and human information processing. In the present study, the Go/No-Go paradigm has
      been used to examine whether alcoholics have poor inhibitory control as compared
      to control subjects in terms of different oscillatory brain responses. The
      matching pursuit algorithm was used to decompose the event-related
      electroencephalogram into oscillations of different frequencies. It was found
      that alcoholics (n=58) showed significant reduction in delta (1.0-3.0 Hz) and
      theta (3.5-7.0 Hz) power during No-Go trials as compared to controls (n=29). This
      reduction was prominent at the frontal region. The decreased delta and theta
      power associated with No-Go processing perhaps suggests a deficient inhibitory
      control and information-processing mechanism. A neuro-cognitive model has been
      provided to explain the findings. It is suggested that the oscillatory correlates
      during cognitive processing can be an endophenotypic marker in alcoholism.

PMID- 14693370
TI  - Glutathione peroxidases of the potato cyst nematode Globodera Rostochiensis.
AB  - We report the cloning and characterisation of full-length DNAs complementary to
      RNA (cDNAs) encoding two glutathione peroxidases (GpXs) from a plant parasitic
      nematode, the potato cyst nematode (PCN) Globodera rostochiensis. One protein has
      a functional signal peptide that targets the protein for secretion from animal
      cells while the other is predicted to be intracellular. Both genes are expressed
      in all parasite stages tested. The mRNA encoding the intracellular GpX is present
      throughout the nematode second stage juvenile and is particularly abundant in
      metabolically active tissues including the genital primordia. The mRNA encoding
      the secreted GpX is restricted to the hypodermis, the outermost cellular layer of
      the nematode, a location from which it is likely to be secreted to the parasite
      surface. Biochemical studies confirmed the secreted protein as a functional GpX
      and showed that, like secreted GpXs of other parasitic nematodes, it does not
      metabolise hydrogen peroxide but has a preference for larger hydroperoxide
      substrates. The intracellular protein is likely to have a role in metabolism of
      active oxygen species derived from internal body metabolism while the secreted
      protein may protect the parasite from host defences. Other functional roles for
      this protein are discussed.

PMID- 14693371
TI  - Alternative splicing of fibronectin: a mouse model demonstrates the identity of
      in vitro and in vivo systems and the processing autonomy of regulated exons in
      adult mice.
AB  - We have designed a novel approach using genetically engineered mice to make a
      systematic study of the EDA exon regulation of the fibronectin gene during
      development and aging. The genome of the mice was modified either by optimization
      of the EDA natural splice sites or by deleting the EDA region. The previous in
      vitro observation that the optimization of the splicing sites leads to
      constitutive inclusion of the EDA exon was confirmed in our animal model. In
      fact, all the adult tissues of the genetically modified mice showed only EDA(+)
      FN mRNA, demonstrating the fidelity of in vitro models, despite of the
      development- and aging-regulated splicing regulation of the EDA exon, and
      regardless of the presence of exonic elements described within the exon. This
      result indicates that the splicing regulatory elements of the EDA exon are
      dispensable in the presence of consensus splicing sites. Moreover, we demonstrate
      the autonomy of both the EDB and the IIICS alternatively spliced regions in adult
      mice lacking regulation of the alternative splicing at the EDA exon. We also show
      here the tight splicing regulation of all three alternative spliced regions of
      the FN gene at different time-points during development and aging of mice.

PMID- 14693373
TI  - Identification of a novel Sertoli cell gene product SERT that influences follicle
      stimulating hormone actions.
AB  - Sertoli cells provide the cytoarchitectural support and microenvironment
      necessary for the process of spermatogenesis and have a central role in male sex
      determination. Characterization of Sertoli cell specific gene products provides
      insight into the unique functions of this testicular cell type. The current study
      reports the identification of a novel Sertoli cell gene product that is termed
      Sertoli cell specific gene (SERT). The SERT cDNA sequence shows no homology to
      any of the known gene sequences in the GenBank database. Some homology was found
      with short sequences in the expressed sequence tag (EST) database. A motif
      analysis demonstrates a signature to an RNA binding protein sex lethal (sx1)
      involved in Drosophila sex determination. The expression pattern of SERT was
      examined with reverse transcription polymerase chain reaction (RT-PCR) and
      Northern blot analysis. SERT expression was found to be specific to the testis
      and absent in other tissues examined. In the testis, the approximate 1.5-kb SERT
      transcript was localized to the Sertoli cells. A 1.1-kb spliced form of SERT was
      also identified by reverse transcription polymerase chain reaction analysis. The
      genomic structure analysis demonstrates the presence of at least three exons with
      85% sequence homology between mouse and rat sequences. Treatment of cultured
      Sertoli cells with follicle stimulating hormone (FSH) significantly increased the
      expression of SERT mRNA levels. The potential role of SERT in Sertoli cell
      function was investigated with the use of a transferrin promoter reporter
      construct. Transferrin expression is a marker of Sertoli cell differentiated
      function. An antisense oligonucleotide to SERT significantly inhibited FSH and
      cAMP induced transferrin promoter activation, while control oligonucleotides had
      no effect. In summary, a novel gene product expressed primarily by Sertoli cells,
      SERT, was identified with a potential RNA binding protein motif similar to sex
      lethal that appears to have a role in maintaining hormone (e.g. FSH) actions in
      Sertoli cells.

PMID- 14693372
TI  - Detailed mapping of the ERG-ETS2 interval of human chromosome 21 and comparison
      with the region of conserved synteny on mouse chromosome 16.
AB  - We have carried out a detailed annotation of 550 kb of genomic DNA on human
      chromosome 21 containing the ERG and ETS2 genes. Comparative genomic analysis
      between this region and the interval of conserved synteny on mouse chromosome 16
      indicated that the order and orientation of the ERG and ETS2 genes were conserved
      and revealed several regions containing potential conserved noncoding sequences.
      Four pseudogenes including those for small protein G, laminin receptor, human
      transposase protein and meningioma-expressed antigen were identified. A
      potentially novel gene (C21orf24) with alternative mRNA transcripts, consensus
      splice donor and acceptor sites, but no coding potential nor murine orthologue,
      was identified and found to be expressed in a range of human cell lines. We have
      identified four novel splice variants that arise from a previously undescribed 5'
      exon of the human ERG gene. Comparison of the cDNA sequences enabled us to
      determine the complete exon-intron structure of the ERG gene. We have also
      identified the presence of noncoding RNAs in the first and second introns of the
      ETS2 gene. Our studies have important implications for Down syndrome as this
      region contains multiple mRNA transcripts, both coding and potentially noncoding,
      that may play as yet undescribed roles in the pathogenesis of this disorder.

PMID- 14693374
TI  - Replicated studentized-deviate detection applied to the identification of
      differentially expressed genes in TNF-alpha-stimulated cells.
AB  - Among the applications of DNA microarray expression data, identification of
      differentially expressed genes is widely used to search for genes involved in
      specific biological processes. Previous studies have shown that replication is
      necessary to reliably identify differentially expressed genes. In practice,
      however, further guidelines are required to provide references for experiment
      design, that is, to fulfill the needs for determining the replication number on a
      desired confidence level or the detection sensitivity of the microarrays. Here,
      we performed simulations to build a simple statistical table of general
      guidelines adapted specifically for identifying differentially expressed genes
      using replications of a microarray experiment, and we present an accompanying
      nonparametric method, replicated studentized-deviate detection (RSD). The
      analysis results of the TNF-alpha-stimulated cells showed that RSD is simple and
      robust, and that the resulting statistical table is plausible.

PMID- 14693375
TI  - The European flounder (Platichthys flesus) TP53 functions as a temperature
      sensitive transcription factor which inhibits cell growth in yeast.
AB  - Numerous studies focus on biological roles of the TP53 tumor suppressor gene in
      mammals but little is known about the actual function of TP53 in lower
      vertebrates. In this study, we used an in vivo functional assay in yeast to
      address the transactivation capacity of the flounder TP53 protein. We showed that
      the flounder TP53 acts as a sequence-specific transcription factor which is able
      to transactivate various human promoters containing a p53-responsive element
      (RE). This transcriptional activity was completely abrogated in the Val147Glu
      TP53 mutant previously identified in two flounder hepatic hyperplasia. In
      addition, we showed that the wild-type (wt) flounder TP53 but not the Val147Glu
      mutant inhibits cell growth when expressed in yeast. We finally reported that
      transcription regulation and growth inhibition by the wild-type flounder TP53 is
      temperature-dependent. The flounder TP53 optimal temperature appeared lower than
      those reported for the Xenopus and human homologues.

PMID- 14693376
TI  - Transcript abundance of rml1, encoding a putative GT1-like factor in rice, is up
      regulated by Magnaporthe grisea and down-regulated by light.
AB  - We isolated and sequenced both genomic DNA and cDNA clones, which encoded a
      putative GT1-like protein with 385 amino acids, from cultivated rice (Oryza
      sativa ssp. indica). This protein shows significant amino acid sequence
      similarities with trihelix DNA-binding GT-1a/B2F and GT-1 factors that were
      identified in dicot plants. Northern blotting analysis indicated that the
      transcript of the rice GT-1 factor in seedling was up-regulated by the rice blast
      fungus Magnaporthe grisea, down-regulated by various continuous light conditions
      and expressed rhythmically in light/dark cycles. This GT1-like factor gene was
      therefore designated as rml1 (rice gene regulated by M. grisea and light). The
      putative RML1 protein, encoded by this single copy gene, is thus identified as a
      new member of the plant-specific GT family of transcription factors in rice.

PMID- 14693377
TI  - TDPOZ, a family of bipartite animal and plant proteins that contain the TRAF (TD)
      and POZ/BTB domains.
AB  - We have previously reported a gene Tdpoz1 (previously called 2cpoz56) that is
      temporally expressed in unfertilized eggs and in early embryos of the mouse. The
      putative TDPOZ1 protein carries a tumor necrosis factor receptor-associated
      factor (TRAF) domain (TD) and a POZ/BTB domain. On the analysis of nine bacterial
      artificial chromosome (BAC) clones, we have uncovered four more Tdpoz1 homologs
      in the mouse genome, designated Tdpoz2 through Tdpoz5. Tdpoz1 and Tdpoz2 are
      found 30 kb apart in a fully sequenced BAC clone (GenBank accession number
      AF545858). The genes are intronless in the coding region and each carries an
      intron in the 5'-untranslated region as in other early embryonic genes. The Tdpoz
      gene cluster is mapped on chromosome 3 at 3F2.1-2.2. RT-PCR experiments and a
      search of expressed sequence tag (EST) databases show that the Tdpoz1-5 genes are
      transcribed in early embryos, particularly at the two-cell stage. Exhaustive
      database searches have further uncovered three more mouse Tdpoz homologs in
      chromosomes 3 and 11 and 25 other Tdpoz-like orthologs in the genomes of other
      animal and plant species including human, rat, C. elegans, Drosophila,
      Arabidopsis and rice. In the rat genome, eight rat Tdpoz genes are found as a
      cluster in chromosome 2. Hence, TDPOZ proteins form a new protein family on the
      basis of similar protein domain organization. Based on reported characteristics
      of known TD- and POZ-bearing proteins, we speculate that TDPOZ proteins may be
      nuclear scaffold proteins probably involved in transcription regulation in early
      development and other cellular processes.

PMID- 14693378
TI  - Cloning and characterization in Pichia pastoris of PNO1 gene required for
      phosphomannosylation of N-linked oligosaccharides.
AB  - The yeast Pichia pastoris PNO1 (Phosphomannosylation of N-linked
      Oligosaccharides) gene, which is involved in phosphomannosylation of N-linked
      oligosaccharides, was cloned using the Saccharomyces cerevisiae MNN4 gene
      [Glycobiology 6 (1996) 805] as a probe. The PNO1 open reading frame (ORF) encodes
      a type II membrane protein composed of 777 amino acid residues. Only in the short
      region extending from amino acid position 450 to 606 of Pno1p, sequence homology
      to S. cerevisiae Mnn4p was observed at a level of 45%. The tandem repeat sequence
      of Lys-Lys-Lys-Lys-Glu-Glu-Glu-Glu characteristic of the C-terminal region of S.
      cerevisiae Mnn4p is not present in Pno1p. To investigate the function of the PNO1
      gene, we constructed a PNO1 gene disruptant by replacement with an expression
      cassette of human antithrombin (AT), a glycoprotein in plasma. The cell growth
      and recombinant human antithrombin (rAT) production levels of the disruptant were
      similar to those of recombinant human antithrombin-expressing wild-type strains.
      Moreover, the level of alcian blue dye cell staining, which shows the presence of
      acidic sugar chains on the cell surface, was also similar. However, the
      phosphomannosylation ratio of N-linked oligosaccharides on recombinant human
      antithrombin decreased dramatically from 20% in wild-type strains to less than 1%
      in the PNO1 disruptant. When the PNO1 gene was re-introduced into the disruptant,
      the phosphomannosylation ratio recovered to the original level. These results
      suggest that the newly cloned PNO1 gene promotes phosphomannosylation only to
      core-like oligosaccharides, and not to the hypermannosylated outer chain, and
      that it has a different function from the MNN4 gene, which promotes the
      phosphomannosylation of both core and outer sugar chains.

PMID- 14693379
TI  - Transfer of RPS14 and RPL5 from the mitochondrion to the nucleus in grasses.
AB  - Gene transfer from the mitochondrion to the nucleus, a process of outstanding
      importance to the evolution of the eukaryotic cell, is an on-going phenomenon in
      higher plants. After transfer, the mitochondrial gene has to be adapted to the
      nuclear context by acquiring a new promoter and targeting information to direct
      the protein back to the organelle. To better understand the strategies developed
      by higher plants to transfer organellar genes during evolution, we investigated
      the fate of the mitochondrial RPL5-RPS14 locus in grasses. While maize
      mitochondrial genome does not contain RPS14 and RPL5 genes, wheat mitochondrial
      DNA contains an intact RPL5 gene and a nonfunctional RPS14 pseudogene. RPL5 and
      PsiRPS14 are co-transcribed and their transcripts are edited. In wheat, the
      functional RPS14 gene is located in the nucleus, within the intron of the
      respiratory complex II iron-sulfur subunit gene (SDH2). Its organization and
      expression mechanisms are similar to those previously described in maize and
      rice, allowing us to conclude that RPS14 transfer and nuclear activation occurred
      before divergence of these grasses. Unexpectedly, we found evidence for a more
      recent RPL5 transfer to the nucleus in wheat. This nuclear wheat RPL5 acquired
      its targeting information by duplication of an existing targeting presequence for
      another mitochondrial protein, ribosomal protein L4. Thus, mitochondrial and
      nuclear functional RPL5 genes appear to be maintained in wheat, supporting the
      hypothesis that in an intermediate stage of the transfer process, both nuclear
      and mitochondrial functional genes coexist. Finally, we show that RPL5 has been
      independently transferred to the nucleus in the maize lineage and has acquired
      regulatory elements for its expression and a mitochondrial targeting peptide from
      an unknown source.

PMID- 14693380
TI  - Genomic organization, expression, and comparative analysis of noncoding region of
      the rat Ndrg4 gene.
AB  - Rat Ndrg4 is a member of the NDRG gene family and has been suggested to relate to
      brain development. The structure of the rat Ndrg4 gene was studied to understand
      the mechanism for the expression of multiple forms of Ndrg4 protein, which were
      revealed in the brain. Subcloning and DNA sequencing analysis of a bacterial
      artificial chromosome (BAC) clone, together with analysis of a transcriptional
      start site by a cap-site hunting, indicated that the Ndrg4 gene spans about 39
      kilobases (kb) and consists of 19 exons, in which the first and second exons were
      first found in rat. An alternative promoter usage at different transcriptional
      start sites may produce three types of messages, Ndrg4-A, Ndrg4-B, and Ndrg4-C,
      and there is a variant that lacks exon 18 for each type of transcript. Thereby,
      Ndrg4-A1, Ndrg4-A2, Ndrg4-B1, Ndrg4-B2, Ndrg4-C1, and Ndrg4-C2 were identified to
      be expressed. These six variants might explain the heterogeneity of the Ndrg4
      protein in the brain. The variants without exon 18 were revealed in the embryonic
      and early postnatal brains while those with exon 18 were detected in the maturing
      and adult brains. Radiation hybrid mapping suggests that the rat Ndrg4 gene is
      located on chromosome 19 at 90.6 centirays (cR) from the top. Comparison of the
      noncoding sequence of the rat Ndrg4 gene to those of the orthologous mouse and
      human genes suggests that the AP-1 binding site is a candidate regulatory
      element.

PMID- 14693381
TI  - Reconstructing the diversification of subtilisins in the pathogenic fungus
      Metarhizium anisopliae.
AB  - Fungi secrete subtilisin proteinases to acquire nutrients and breach host
      barriers. Here we sought a global characterization of the diversity of
      subtilisins in the insect pathogen Metarhizium anisopliae. Expressed sequence tag
      (EST) analyses showed that a broad host range strain of M. anisopliae sf.
      anisopliae (strain 2575) expressed 11 subtilisins during growth on insect
      cuticle, the largest number of subtilisins reported from any fungus. Polymerase
      chain reaction amplified 10 of their orthologs from a second strain with multiple
      hosts (strain 820) and seven from the locust specialist M. anisopliae sf. acridum
      (strain 324). Analyses based on sequence similarities and exon-intron structure
      grouped M. anisopliae subtilisins into four clusters-a class I ("bacterial")
      subtilisin (Pr1C), and three clusters of proteinase K-like class II subtilisins:
      extracellular subfamily 1 (Pr1A, Pr1B, Pr1G, Pr1I and Pr1K), extracellular
      subfamily 2 (Pr1D, Pr1E, Pr1F and Pr1J) and an endocellular subtilisin (Pr1H).
      Phylogenetic analysis of homologous sequences from other genera revealed that
      this subdivision of proteinase K-like subtilisins into three subfamilies preceded
      speciation of major fungal lineages. However, diversification has continued
      during the evolution of Metarhizium subtilisins with evidence of gene duplication
      events after divergence of M. anisopliae sf. anisopliae and M. anisopliae sf.
      acridum. Comparing alignments and nonsynonymous/synonymous rates for Pr1
      isoenzymes within a lineage and between lineages showed that while overall
      divergence of subtilisins followed neutral expectations, amino acids involved in
      catalysis were under strong selective constraint. This suggests that each Pr1
      paralog contributes to the pathogens fitness. Furthermore, homology modeling
      predicted differences between the Pr1's in their secondary substrate
      specificities, adsorption properties to cuticle and alkaline stability,
      indicative of functional differences.

PMID- 14693382
TI  - An rxr/usp homolog from the parasitic nematode, Dirofilaria immitis.
AB  - Filarial parasites are responsible for several serious human diseases with
      symptoms such as lymphoedema, elephantiasis, and blindness. An understanding of
      how these parasites pass through developmental checkpoints may suggest potential
      targets for intervention. A useful model system for the study of the human
      parasites is the closely related nematode Dirofilaria immitis, the causative
      agent of dog heartworm disease. In D. immitis, molting from the third to the
      fourth larval stage can be induced in vitro by the insect molting hormone, 20
      hydroxyecdysone, suggesting that this, or some related steroid, may play a
      similar role in the development of D. immitis. The holoreceptor of 20
      hydroxyecdysone consists of two nuclear receptors (NRs) ecdysone receptor (EcR)
      and ultraspiracle (USP), USP being the insect orthologue of the vertebrate RXR.
      We have identified a D. immitis rxr/usp, Di-rxr-1 (NR2B4). Di-RXR-1 can bind in
      vitro to EcR and DHR38, both known insect USP partners. Like, USP, it activates
      transcription in Drosophila Schneider S2 cells in a 20-hydroxyecdysone-dependent
      manner, via its interaction with the endogenous EcR protein. By Northern blot
      analysis, Di-rxr-1 mRNA is detected in adult females, but not in males. This is
      the first characterization of a nematode rxr/usp.

PMID- 14693383
TI  - Activation of gene expression by triplex-directed psoralen crosslinks.
AB  - Psoralen-conjugated triplex-forming oligonucleotides (pso-TFOs) can target
      photochemical adducts to specific DNA sequences. Here, we have used pso-TFOs to
      activate gene expression on a plasmid. We designed a pso-TFO adapter, consisting
      of a single-stranded TFO for targeting DNA, linked to a double-stranded hairpin
      segment that contains a hybrid ecdysone response element (E/GRE) enhancer for
      binding activated ecdysone receptors. When targeted to the 5' flanking region of
      a minimal promoter, this pso-TFO adapter increased the expression of a downstream
      reporter gene three- to four-fold. Gene activation, however, was independent of
      both the E/GRE hairpin of the adapter and ecdysone receptors, suggesting it was
      due to an intrinsic effect of triplex. Gene activation was dependent on psoralen
      photo-crosslinking. Gene activation by pso-TFOs in which the psoralen was linked
      to the TFO via a disulfide bond was similar before and after detachment of the
      TFO and its release from the triplex. These results indicate that psoralen photo
      crosslinks play a prominent role in activation. Gene activation was undiminished
      in XPA, XPD and XPG human cell lines, indicating that activation was not
      dependent on the complete nucleotide excision repair (NER) pathway. Collectively,
      these results demonstrate that TFOs can be used to direct psoralen crosslinks
      adjacent to a gene as a way of activating gene expression.

PMID- 14693384
TI  - Alu's dimeric consensus sequence destabilizes its transcripts.
AB  - The effect that different regions of the Alu consensus sequence have upon the
      stability and accumulation of its RNA polymerase III (Pol III) directed
      transcripts was determined by transiently overexpressing Alu deletion and
      chimeric constructs in human 293 cells. Transcripts of the left Alu monomer are
      more stable than those of the full-length consensus sequence and any additional
      3' sequence beyond the left monomer destabilizes the resulting transcript.
      Neither the middle A-rich region nor the 3' A-rich tail specifically affect the
      stability of Alu transcripts. However, the right monomer is inherently less
      stable than corresponding left monomer transcripts. Alu's dimeric structure and
      sequences peculiar to the right monomer each limit the stability and steady state
      accumulation of its transcripts. A host requirement to rapidly metabolize Alu RNA
      or restrict its abundance may have selected for these two features of the Alu
      consensus sequence.

PMID- 14693386
TI  - Clinicopathological correlation between brainstem gliosis using GFAP as a marker
      and sleep apnea in the sudden infant death syndrome.
AB  - BACKGROUND: Chronic hypoxia, leading to brainstem gliosis, has been postulated as
      a factor in the sudden infant death syndrome (SIDS), which is still the main
      cause of postneonatal infant death. Gliosis detected by immunohistochemistry of
      glial fibrillary acidic protein (GFAP) is a marker of apoptosis. The correlation
      between GFAP-positive reactive astrocytes in the brainstem and sleep apnea in
      SIDS was investigated. MATERIALS AND METHODS: Among 27,000 infants studied
      prospectively to characterize their sleep-wake behavior, 38 infants died under 6
      months of age, including 26 cases of SIDS. The frequency and duration of sleep
      apnea were analyzed. Brainstem material was collected and immunohistochemistry of
      GFAP carried out. The density of GFAP-positive reactive astrocytes was measured
      quantitatively. Correlation analyses were carried out between the data on gliosis
      and the physiological data of sleep apnea. RESULTS: A SIDS-specific negative
      correlation between the density of gliosis in the dorsal vagus nucleus in the
      medulla oblongata and the frequency of obstructive apnea (p=0.022) was found.
      CONCLUSIONS: A significant SIDS-specific correlation with gliosis in the dorsal
      vagus nucleus and the characteristics of sleep apnea might invite the
      cardiorespiratory changes in SIDS.

PMID- 14693387
TI  - Pathological data on apoptosis in the brainstem and physiological data on sleep
      apnea in SIDS victims.
AB  - The sudden infant death syndrome (SIDS) is still the main cause of postneonatal
      infant death and its cause is still unknown. A chronic hypoxic situation has been
      shown to exist in the brains of SIDS victims and apoptosis has been demonstrated
      in hypoxic situations. In this study, the correlation between apoptotic neurons
      or glias and sleep apnea in SIDS was investigated in the brainstem of SIDS
      victims. MATERIALS AND METHODS: In a cohort of 27,000 infants studied
      prospectively to characterize their sleep-wake behavior, 38 infants died under 6
      months of age. They included 26 cases of SIDS. The frequency and duration of
      sleep apnea were analyzed. The brainstem material was collected and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method was
      carried out. The density of TUNEL-positive neurons or glias was measured
      quantitatively. Correlation analyses were carried out between the apoptosis
      associated pathological data and the physiological data of sleep apnea. RESULTS:
      No significant negative or positive correlation between the density of TUNEL
      positive neurons or glias and the characteristics of sleep apnea was observed in
      SIDS victims. No statistically significant differences associated with apoptotic
      neurons and glias were observed between SIDS and non-SIDS. CONCLUSIONS: The
      pathological findings of apoptosis were not in agreement with the hypothesis
      refer to apnea and arousal phenomenon in pathophysiology of SIDS.

PMID- 14693388
TI  - Investigation into the correlation in SIDS victims between Alzheimer precursor
      protein A4 in the brainstem and sleep apnea.
AB  - BACKGROUND: Recently, the appearance of beta-amyloid precursor protein (APP) has
      been demonstrated in the neonatal brain following hypoxic-ischaemic injury. As
      chronic hypoxia is one of the favoured theories of causation in the sudden infant
      death syndrome (SIDS), the correlation between APP in the brainstem and sleep
      apnea in SIDS was investigated. MATERIALS AND METHODS: Among 27,000 infants
      studied prospectively to characterize their sleep-wake behavior, 38 infants died
      under 6 months of age, which included 26 cases of SIDS. All the infants had been
      recorded during one night in a pediatric sleep laboratory, some 3 to 12 weeks
      before death. The frequency and duration of sleep apnea were analyzed. The
      brainstem material was collected and immunohistochemistry with anti-Alzheimer
      precursor protein A4 (APP) was carried out. The density of APP-positive elements
      was measured semi-quantitatively. Correlation analyses were carried out between
      the density of APP-positive elements and the data on sleep apnea. RESULTS: No
      correlation was found. CONCLUSION: No correlation between pathological data of
      APP and physiological data of sleep apnea was not in agreement with the
      association of sleep apnea in pathophysiology of SIDS.

PMID- 14693390
TI  - Catecholaminergic neurons in the brain-stem and sleep apnea in SIDS victims.
AB  - BACKGROUND: Tyrosine hydroxylase (TH) is a specific marker for catecholaminergic
      neurones. Some reports have demonstrated a decrease of TH in the Sudden Infant
      Death Syndrome (SIDS) compared with controls. To further investigate this, the
      correlation between TH and sleep apnea was investigated here. MATERIALS AND
      METHODS: Among 27,000 infants studied prospectively to characterize their sleep
      wake behavior, 38 infants died under 6 months of age. They included 26 cases of
      SIDS. All the infants had been recorded during one night in a pediatric sleep
      laboratory some 3 to 12 weeks before death. The frequency and the duration of
      sleep apnea were analyzed. The brain stem material was collected and subjected to
      immunohistochemical studies for TH. The density of TH-immunoreactive neurons was
      measured in the nucleus hypoglossus, nervus vagus dorsalis, solitary and
      ambiguous and the ventrolateral medulla (VLM) in the medulla oblongata.
      Correlation analyses were carried out between the density of TH-immunoreactive
      neurons and the data from the sleep apnea studies. RESULTS: There was no SIDS
      specific correlation between TH-immunoreactive neurons in the nucleus
      hypoglossus, nervus vagus dorsalis, solitary and ambiguous and the ventrolateral
      medulla (VLM) in the medulla oblongata and the frequency and duration of sleep
      apnea. CONCLUSIONS: No significant association between the pathological data and
      the physiological data refers to TH positive neurons in the medulla oblongata in
      SIDS victims.

PMID- 14693391
TI  - Substance P in the midbrains of SIDS victims and its correlation with sleep
      apnea.
AB  - BACKGROUND: Substance P (SP) is a neuropeptide transmitter found in sensory
      neurons of the central nervous system and related to pain sensation and
      respiratory regulation. Some reports claim an increase in SP in the brains of
      SIDS victims, so the correlation between SP and sleep apnea was investigated
      here. MATERIALS AND METHODS: Among 27,000 infants studied prospectively to
      characterize their sleep-wake behavior, 38 infants died under 6 months of age,
      which included 26 cases of Sudden Infant Death Syndrome (SIDS). All the infants
      had been recorded during one night in a pediatric sleep laboratory some 3 to 12
      weeks before death. The frequency and duration of sleep apnea were analyzed.
      Brainstem material was collected and immunohistochemistry for SP was carried out.
      The density of SP positive fibers was measured in the nucleus spinal and
      mesencephalic nervi trigemini and nucleus parabranchialis in the brainstem of
      abovementioned cases. Correlation analyses were carried out between the density
      of SP and the data of sleep apnea. RESULTS: There was no SIDS specific
      correlation of SP through the above-listed parts of the midbrain with frequency
      and duration of sleep apnea. CONCLUSIONS: There was no significant association
      between the SP findings and apnea data in SIDS; this is not in agreement with the
      association of apnea in pathophysiology of SIDS.

PMID- 14693389
TI  - The correlation between serotonergic neurons in the brainstem and sleep apnea in
      SIDS victims.
AB  - BACKGROUND: In the Sudden Infant Death Syndrome (SIDS), a medullary serotonergic
      network deficiency theory has been proposed, amongst many other hypotheses. The
      correlation between serotonergic neurons or dendritic spines in the brainstem of
      SIDS and sleep apnea was investigated here. MATERIALS AND METHODS: Twenty-seven
      thousand infants were studied prospectively to characterize their sleep-wake
      behavior. Of these, 38 infants died under 6 months of age, including 26 cases of
      SIDS. The frequency and duration of sleep apnea were analyzed. Brainstem material
      was collected and immunohistochemistry for tryptophan hydroxylase (TrypH) carried
      out. The density of TrypH-positive neurons was measured quantitatively.
      Correlation analyses were carried out between the TrypH-associated pathological
      data and the physiological data of sleep apnea. RESULTS: One significant positive
      correlation between the density of TrypH-positive neurons in the dorsal raphe
      nucleus of the midbrain and the duration of central apnea (p=0.027) was found in
      SIDS victims. CONCLUSIONS: Some of serotonergic facts could be involved in the
      pathophysiology of SIDS.

PMID- 14693392
TI  - Partial arousal deficiency in SIDS victims and noradrenergic neuronal plasticity.
AB  - Sudden infant death syndrome (SIDS) victims had exhibited during sleep a
      reduction in cortical arousals despite an increase in subcortical activation.
      Arousal deficiency in SIDS victims was partial. We could suggest the latent
      existence of inadequate noradrenergic neuronal plasticity as the background of
      this partial arousal deficiency of SIDS victims.

PMID- 14693393
TI  - Serotonergic receptors in the midbrain correlated with physiological data on
      sleep apnea in SIDS victims.
AB  - BACKGROUND: Recently it has been reported that serotonin and related matters are
      associated with the sudden infant death syndrome (SIDS), which is still the main
      cause of postneonatal infant death. To further explore this claim, the
      correlation between serotonin receptors in the brainstem and sleep apnea in SIDS
      victims was investigated. MATERIALS AND METHODS: Among 27,000 infants studied
      prospectively to characterize their sleep-wake behavior, 38 infants died under 6
      months of age including 26 cases of SIDS. All the infants had been recorded
      during one night in a pediatric sleep laboratory some 3-12 weeks before death.
      The frequency and duration of sleep apnea were analyzed. Brainstem material was
      collected and immunohistochemistry on 5-hydroxy tryptamine 1A (5HT1A) receptor
      was carried out. The density of 5HT1A receptor-positive neurons was measured
      quantitatively. Nonparametric analysis of the density of 5HT1A receptor-positive
      neurons was carried out between SIDS and non-SIDS cases. Correlation analyses
      were performed between the density of 5HT1A receptor-positive neurons and the
      data on sleep apnea. RESULTS: There was no correlation between the pathological
      data on 5HT1A receptors and the physiological data on sleep apnea in SIDS
      victims. CONCLUSIONS: No correlation between pathological findings of serotonin
      and physiological findings of sleep apnea were not in agreement with the
      association of sleep apnea in pathophysiology of SIDS.

PMID- 14693394
TI  - The correlation between ubiquitin in the brainstem and sleep apnea in SIDS
      victims.
AB  - BACKGROUND: The sudden infant death syndrome (SIDS) is still the main cause of
      postneonatal infant death and its etiology has stimulated many competing
      theories, among which is the role of hypoxia and brainstem abnormalities. One
      report claims an increased in ubiquitin in the liver of SIDS victims, ubiquitin
      being one of the heat-shock proteins. The correlation between ubiquitin in the
      brainstem and sleep apnea in SIDS was investigated here. MATERIALS AND METHODS:
      Among 27,000 infants studied prospectively to characterize their sleep-wake
      behavior, 38 infants died under 6 months of age, including 26 cases of SIDS. All
      the infants had been recorded during one night in a pediatric sleep laboratory
      some 3-12 weeks before death. The frequency and duration of sleep apnea were
      analyzed. Brainstem material was collected at autopsy and examined
      immunohistochemically for ubiquitin. The density of ubiquitin-positive elements
      was measured semiquantitatively. Correlation analyses were carried out between
      the density of ubiquitin-positive elements and the data on sleep apnea. RESULTS:
      In the victims of SIDS, a statistically significant positive correlation was
      found between the density of ubiquitin-positive neuronal factors in the pons and
      the frequency of obstructive apnea (p=0.001) and statistically significant
      negative correlations were seen between the density of ubiquitin-positive cells
      in the ependyma in the pons and the duration of obstructive apnea (p=0.044) and
      between the density of ubiquitin-positive cells in the subependyma in the medulla
      and the frequency of central apnea (p=0.024). CONCLUSIONS: It was found that
      three significant associations existed between the pathological data referring to
      ubiquitin and physiological data in SIDS victims. These facts are in agreements
      with the association of sleep apnea in SIDS.

PMID- 14693395
TI  - The correlation between microtubule-associated protein 2 in the brainstem of SIDS
      victims and physiological data on sleep apnea.
AB  - BACKGROUND: Microtubule-associated protein 2(MAP2), a cytoskeletal protein of the
      neuron, is a marker of early ischemic neuronal damage. As a chronic hypoxic
      situation exists in the brains of victims of the sudden infant death syndrome
      (SIDS), the correlation between MAP2-positive neurons or dendritic spines in the
      brainstem and sleep apnea was investigated in SIDS, which is still the main cause
      of postneonatal infant death. MATERIALS AND METHODS: 27,000 infants were studied
      prospectively to characterize their sleep-wake behavior and amongst these, 38
      infants died under 6 months of age. They included 26 cases of SIDS. The frequency
      and duration of sleep apneae were analyzed. The brainstem material was collected
      and immunohistochemistry of MAP2 was carried out. The density of MAP2-positive
      neurons, dendrites and dendritic spines were measured quantitatively. Correlation
      analyses were carried out between the MAP2-associated pathological data and the
      physiological data of sleep apnea. RESULTS: One negative correlation between the
      density of MAP2-positive dendrites in the pars compacta of pedunculo-pontine
      tegmentum nucleus (PPTNc) and the duration of obstructive apnea (p=0.017) and two
      SIDS-specific positive correlations between the density of MAP2-positive
      dendrites in the pars dissipata of pedunculo-pontine tegmentum nucleus (PPTNd)
      and the duration of central apnea (p=0.005) and between the dorsal raphe and the
      frequency of obstructive apnea were found in SIDS victims. The density of MAP2
      positive dendritic spines in PPTNc was significantly higher in SIDS than in
      control (p=0.034). CONCLUSIONS: The significant correlations with the MAP2
      positive findings in the midbrain arousal pathway and the characteristics of
      sleep apnea in SIDS victims were in agreement with the association with apnea and
      arousal-deficiency in SIDS.

PMID- 14693396
TI  - The correlation between tau protein in the brainstem and sleep apnea in SIDS
      victims.
AB  - BACKGROUND: Recently, it has been reported that neuronal plasticity in the
      brainstem arousal pathway is related to the sudden infant death syndrome (SIDS).
      Tau protein may contribute to axonal development and neural plasticity;
      therefore, the correlation between tau protein in the brainstem and sleep apnea
      in SIDS was investigated here. MATERIALS AND METHODS: Among 27,000 infants
      studied prospectively to characterize their sleep-wake behavior, 38 infants died
      under 6 months of age, including 26 cases of SIDS. The frequency and duration of
      sleep apnea were analyzed on all the infants, having been recorded during one
      night in a pediatric sleep laboratory some 3-12 weeks before death. The brainstem
      material was collected and immunohistochemistry of tau was carried out. The
      density of tau-positive elements was measured semiquantitatively. Correlation
      analyses were carried out between the density of tau-positive elements and the
      data of sleep apnea. RESULTS: In the 26 SIDS cases, tau-positive findings were
      observed in the sub-pia mater in two cases, in the colloid plexus in one case, in
      the ependyma and subependyma in five cases, in neurons in two cases and as a
      general diffusion in one case. In 12 control cases, tau-positive findings were
      observed in the sub-pia mater in one case and in neuronal elements in three
      cases. No correlation was found on analysis. CONCLUSIONS: There was no
      correlation between the finding of tau in the brainstem of SIDS victims and the
      incidence of sleep apnea.

PMID- 14693397
TI  - The presence of TATA-binding protein in the brainstem, correlated with sleep
      apnea in SIDS victims.
AB  - BACKGROUND: Recent reports have indicated that the presence of transcription
      factors and RNA polymerase decreases in rat brains that suffer perinatal asphyxia
      from hypoxia. As hypoxia has been proposed as a causative factor in the Sudden
      Infant Death Syndrome (SIDS), the correlation between TATA-binding protein (TBP)
      in the brainstem of SIDS victims as a marker of transcription and the incidence
      of sleep apnea was investigated. MATERIALS AND METHODS: A total of 38 infants,
      including 26 cases of SIDS, died under 6 months of age, in a cohort of 27,000
      infants studied prospectively to characterize their sleep-wake behavior. The
      frequency and duration of sleep apnea was analyzed. Brainstem material was
      collected and immunohistochemistry of TBP was carried out. The density of TBP
      positive neurons was measured quantitatively. Correlation analyses were carried
      out between the density of TBP-positive neurons and the data concerning sleep
      apnea. RESULTS: One SIDS-specific positive correlation occurred between the
      density of TBP-positive neurons in the dorsal raphe nucleus of the midbrain and
      the duration of central apnea (p=0.049) and two SIDS-specific negative
      correlations between the density of TBP-positive neurons in the pars compacta and
      dissipata of the pedunculopontine tegmentum nucleus (PPTNc, PPTNd) in the
      midbrain and the duration of apnea (p=0.035). CONCLUSIONS: The significant
      correlation between the findings of TBP-positive neurons in the midbrain arousal
      pathway and the characteristics of sleep apnea in SIDS victims is in agreement
      with the both association of apnea and arousal phenomenon in pathophysiology of
      SIDS.

PMID- 14693398
TI  - Correlation between the Ki-67 antigen in the brainstem and physiological data on
      sleep apnea in SIDS victims.
AB  - BACKGROUND: The Ki-67 antigen appears in all human proliferating cells during
      late G1, S, M and G2 phases of the cell cycle, but is consistently absent in the
      Go phase (noncycling) cells. The correlation between Ki-67 in the brainstem and
      sleep apnea in victims of the sudden infant death syndrome (SIDS) was
      investigated to elucidate cell kinetics in the brainstem of this condition, which
      is still the main cause of postneonatal infant death. MATERIALS AND METHODS:
      Twenty-six cases of SIDS occurred among 38 infants dying under 6 months of age in
      a cohort of 27,000 infants studied prospectively to characterize their sleep-wake
      behavior. All the infants had been recorded during one night in a pediatric sleep
      laboratory some 3 to 12 weeks before death. The frequency and duration of sleep
      apnea were analyzed. At autopsy, brainstem material was collected and
      immunohistochemistry for Ki-67 was carried out. The density of Ki-67-positive
      neurons was measured semiquantitatively. Correlation analyses were carried out
      between the density of Ki-67-positive neurons and the data on sleep apnea.
      RESULTS: Except in two cases in SIDS victims and in one control, the detection of
      Ki-67 was negative. No correlation analysis between the Ki-67 and of sleep apnea
      was found. CONCLUSIONS: There were no abnormal cell kinetics detected by the
      demonstration of Ki-67 antigen in the brainstems of SIDS victims.

PMID- 14693399
TI  - Alpha2-adrenergic receptor subtype alterations in the brainstem in the sudden
      infant death syndrome.
AB  - BACKGROUND: The sudden infant death syndrome (SIDS) is still the main cause of
      postneonatal infant death. However, the causes and mechanisms of SIDS have never
      been completely elucidated. Catecholamines, via alpha2-adrenergic receptor
      (alpha2-AR) interactions, are known to influence brainstem autonomic and
      respiratory activity. AIMS: To examine the catecholaminergic system abnormalities
      in SIDS victims, we investigated the alterations of alpha2-AR subtypes. SUBJECTS
      AND METHODS: We examined the developmental changes of alpha2-AR subtypes in the
      brainstem, especially in cardiorespiratory nuclei, in 21 SIDS victims and 17 age
      matched controls by means of immunohistochemical methods. For statistical
      analysis, the chi2-test or Fisher's exact probability test was performed.
      RESULTS: There was a significant decrease in alpha2A-AR immunoreactivity in the
      solitary nucleus and ventrolateral medulla (VLM) in the medulla oblongata in SIDS
      victims compared with in control cases, but there were no significant differences
      of the alpha2B and alpha2C-AR immunoreactivity in the brainstem between SIDS
      victims and controls. CONCLUSION: Alpha2A-AR immunoreactivity was selectively
      decreased in the solitary nucleus and VLM in the medulla oblongata in SIDS
      victims, so there was no possibility that it was secondary to chronic hypoxia or
      repeated ischemia. It may be related to some impairment of the cardiorespiratory
      neuronal system. Therefore, SIDS victims may be vulnerable to asphyxia, hypoxia,
      and/or hypercapnia, and fail to exhibit brainstem responses.

PMID- 14693400
TI  - The relationship between neuronal plasticity and serotonergic neurons in the
      brainstem of SIDS victims.
AB  - BACKGROUND: The sudden infant death syndrome (SIDS) is still the main cause of
      postneonatal infant death and its cause is still unknown. Recently, the medullary
      serotonergic network deficiency theory has been proposed and an association
      between SIDS and neuronal plasticity has also been suggested. The growth
      associated phosphoprotein 43 (GAP43) is a marker of synaptic plasticity and is
      critical for normal development of the serotonergic innervation. Therefore, the
      characteristics of GAP43-positive elements and their association with
      serotonergic neurons were here investigated in the brainstem of SIDS victims.
      MATERIALS AND METHODS: The materials of this study included 26 cases of SIDS and
      12 control cases. The brainstem material was collected and the
      immunohistochemistry of GAP43 and tryptophan hydroxylase (TrypH) carried out. The
      density of GAP43-positive neurons and dendrites and of TrypH-positive neurons
      were measured quantitatively. Nonparametric analyses of GAP43 between SIDS and
      non-SIDS and correlation analyses between GAP43 and TrypH were performed.
      RESULTS: No significant difference in GAP43-associated findings was found between
      SIDS and non-SIDS nor any significant correlation between GAP43-associated
      findings and TrypH-positive neurons. CONCLUSIONS: The results of this study were
      not in agreement with the association of GAP43 with SIDS and with serotonergic
      innervation in SIDS.

PMID- 14693401
TI  - Sudden infant deaths: stress, arousal and SIDS.
AB  - The prevalence of the Sudden Infant Death Syndrome (SIDS) has dropped in most
      countries following the development of education campaigns on the avoidance of
      preventable risk factors for SIDS. These include factors in the infant's micro
      environment, such as prenatal passive smoking, administration of sedative drugs,
      prone sleep, high ambient temperature or sleeping with the face covered. Sleep
      laboratory studies have shown that these risk conditions contribute to the
      development of respiratory and autonomic disorders and reduce the child's
      arousability. The opposite effects were seen when studying factors protective
      from SIDS, such as breastfeeding or the use of a pacifier. In victims of SIDS,
      similar breathing, autonomic and arousal characteristics were recorded days or
      weeks before their death. It is concluded that in some infants, already immature
      control mechanisms can be aggravated by environmental factors.

PMID- 14693402
TI  - Sleep apnea in mice: a useful animal model for study of SIDS?
AB  - Although the incidence of sudden infant death syndrome (SIDS) has been decreased
      by education programs to avoid sleeping in prone position, the pathological
      mechanisms of SIDS have not fully been understood. Basic research on sleep apnea
      using experimental animals may help further understanding and prevention of SIDS
      because the syndrome is thought as inability to wake up from respiratory arrest
      (apnea) during sleep. Although several animal models of sleep apnea have been
      described previously, mice would be useful experimental animals in that these
      animals are frequently used in genetic engineering. Those considerations prompted
      us to establish a method for measuring ventilation of mice concomitantly with
      electroencephalography and electromyography for assessing sleep-wake states.
      Normal wild-type mice developed two types of central sleep apneas (CSA), that is,
      post-sigh and spontaneous apneas, as normal humans do. Moreover, post-sigh apneas
      in mice were observed exclusively during slow-wave sleep (SWS) while spontaneous
      apneas were seen in both SWS and rapid eye movement (REM) sleep. These
      characteristics are very similar to those of sleep apneas in healthy human
      infants and children. Therefore, mice seem to be a promising experimental animal
      model for studying the genetic and molecular basis of respiratory regulation and
      dysregulation during sleep in humans, especially infants and children. However,
      we should keep in mind limitations in studying mice as an animal model of SIDS,
      since they are nocturnal rodents and they sleep in the prone position.

PMID- 14693403
TI  - Recent trend of the incidence of sudden infant death syndrome in Japan.
AB  - OBJECTIVES: To clarify the trend of the incidence of SIDS in the last 20 years in
      Japan to provide the basis for health administration training. METHOD: We have
      studied the SIDS incidence rate, the infant mortality rate, the neonatal
      mortality rate and perinatal deaths of the last 20 years in Japan and calculated
      the rate at which SIDS has contributed to infant mortality. RESULT: We found that
      the 2001 SIDS incidence rate in Japan was 0.24 per 1000 births, which had taken a
      downturn since its upturn of around 1995. The rate of SIDS incidence as a part of
      the infant mortality rate in 2001 in Japan was 7.7%, which had taken a downturn
      since its upturn of around 1997. CONCLUSION: The SIDS incidence rate in Japan in
      recent years is on the decline.

PMID- 14693404
TI  - Questionnaire study to Japanese SIDS families.
AB  - OBJECTIVES: To clarify the situation of the incidence of the sudden infant death
      syndrome (SIDS) in Japan to provide the basis for health administration training.
      METHOD: The questionnaire study about the circumstances and responses in
      discovering the death of a SIDS infant was carried out by the SIDS Family
      Association Japan. The bereaved parents were asked to reply as to whether or not
      the SIDS was the cause of their children's death, carried out a cross tabulation
      and a chi2 test of significance. RESULT: We found differences between SIDS and
      non-SIDS infants in respect to the place of death, the health condition up to
      death, the sleeping position at the time of death and room sharing. With regards
      to the responses on the death of a child, we found differences between the SIDS
      and non-SIDS infants in respect to whom the infant was in contact with at the
      time of death and especially with the responses of the paramedics. Other
      differences found were in respect to whether or not considerations were given to
      the family in informing them about procedures and treatment, in informing them of
      the procedures and medical information or to the family's feelings in advising an
      autopsy and whether or not a sufficient explanation was provided before the
      autopsy. CONCLUSION: To lighten the trauma suffered by a SIDS family, it is
      necessary that we pay adequate attention to giving consideration to the family
      through general informed consent including giving thoughtful consideration in
      advising an autopsy.

PMID- 14693405
TI  - Preterm to early postterm changes in the development of hand-mouth contact and
      other motor patterns.
AB  - Hand-mouth contacts (HMCs) and other spontaneous movements of five low-risk
      preterm infants were studied longitudinally after their birth until 60 weeks
      postmenstrual age. For all infants, HMCs that emerged in the preterm period could
      not be observed transiently after 45 weeks, however, they re-emerged after 50
      weeks postmenstrual age. In actograms of the infants' behaviors, the frequency of
      other spontaneous movements, such as head rotation, showed the same re-emerging
      pattern. Movements such as cloni, which were also observed in the preterm period,
      decreased after the term period, with no subsequent increase. Only general
      movements were continuously present throughout the entire observation period;
      these changed from writhing to fidgety in nature around the third month. These
      findings clarify which spontaneous movements of preterm infants are important for
      later behavioral development.

PMID- 14693406
TI  - Hemodynamic responses to visual stimulation in occipital and frontal cortex of
      newborn infants: a near-infrared optical topography study.
AB  - A near-infrared optical topography (OT) was used to reveal spatio-temporal
      changes in the cerebral oxygenation of newborn infants in response to brief
      visual stimulation. Newborn infants were presented 3-s stroboscopic light
      flashing at 14 Hz during spontaneous sleep. Event-related changes in oxy- and
      deoxyhemoglobin ([oxy-Hb] and [deoxy-Hb]) were observed over the occipital and
      frontal cortex. The visual stimulus produced statistically significant increases
      in oxyhemoglobin not only in the occipital cortex but also in the prefrontal
      cortex. These results suggest that the cerebrovascular coupling is already
      functioning in newborn's brain. The prefrontal activation implies that it may
      contribute to early processing of sensory signals.

PMID- 14693407
TI  - Daily nasal inoculation with the insulin gene ameliorates diabetes in mice.
AB  - The present study examined the feasibility of liposome-mediated gene transfer via
      nasal administration, for treating insulin-dependent diabetes mellitus. The rat
      insulin gene was packed under control of the CMV promoter, complexed with DC
      chol/DOPE-based liposomes and administered daily via the nasal route in mice made
      severely diabetic by streptozocin. Sustained expression of the insulin gene was
      achieved and insulinopenia, ketonuria and death were prevented. Hyperglycemia and
      body weight reduction were significantly suppressed without evidence of
      hypoglycemia throughout the experimental period. RT-PCR and FISH analysis
      indicated that insulin was produced in the alveolar epithelial cells of the lung.
      Liposome-mediated in vivo gene transfer via nasal administration may provide an
      efficacious route for delivery of hormonal and other gene products into the blood
      stream.

PMID- 14693408
TI  - Genotype Gly/Gly of the Arg16Gly polymorphism of the beta2-adrenergic receptor is
      associated with elevated fasting serum insulin concentrations, but not with acute
      insulin response to glucose, in type 2 diabetic patients.
AB  - The beta(2)-adrenergic receptor (B2AR) is expressed in pancreatic beta-cells and
      modulates insulin secretion. The purpose of the present study was to evaluate the
      influence of the Arg16Gly variant allele of B2AR on insulin secretion in patients
      with type 2 diabetes. We used minimal model analysis of the frequently sampled
      insulin-modified intravenous glucose tolerance test (FSIGT) and polymerase chain
      reaction (PCR)-restriction fragment length polymorphism to examine differences of
      insulin secretion and insulin resistance among three genotypes. There were no
      significant differences in baseline clinical characteristics, HbA1c, uric acid,
      CRP or lipid profiles among the three groups. The Gly/Gly group had significantly
      higher levels of fasting insulin (38.2+/-4.7 pmol/l versus 23.6+/-3.5 pmol/l) and
      homeostasis model assessment of insulin resistance (HOMA-R) (1.90+/-0.19 versus
      1.32+/-0.24), compared with the Arg/Arg group, but there were no significant
      differences in acute insulin response to glucose (AIRg) bolus, insulin
      sensitivity (Si), or glucose effectiveness (Sg) among the three genotypes.
      Several reports have speculated that the Gly16 allele of B2AR exhibits agonist
      promoted downregulation, but our findings, elevated fasting insulin
      concentrations, and previous clinical studies of blood pressure and lypolysis are
      controversial. The direct mechanism by which the Gly16 allele of B2AR may
      influence insulin secretion of pancreatic beta-cells is unknown. Further studies
      of the expression of the allelic receptor in islet cells may help to resolve the
      role of B2AR in insulin secretion. However, increased sensitivity to
      catecholamine-induced lipolysis of the Gly allele promotes higher free fatty
      acids concentrations in the portal system, which could enhance the higher levels
      of fasting insulin.

PMID- 14693409
TI  - Decrease in serum C-reactive protein levels by troglitazone is associated with
      pretreatment insulin resistance, but independent of its effect on glycemia, in
      type 2 diabetic subjects.
AB  - Insulin-sensitizing thiazolidinediones (TZDs) decrease inflammatory markers such
      as high-sensitive C-reactive protein (hsCRP) in sera in addition to their
      hypoglycemic effects. However, factors associated with the decrease in serum
      hsCRP concentrations are unclear. In the present study, an effect of troglitazone
      on serum hsCRP levels was investigated and compared with its effect on glycemia.
      A total of 34 subjects with type 2 diabetes (17 men and 17 women, aged 54+/-2
      years and body mass index (BMI) 26.7+/-0.6 kg/m(2), mean+/-S.E.) were studied.
      Nineteen out of the 34 subjects was treated with troglitazone 400mg daily for 12
      weeks. The remaining 15 subjects were treated with metformin 750 mg daily as a
      control group. Baseline hsCRP levels were comparable between the two groups, and
      those were positively associated with fasting insulin levels. After treatment,
      glycemic control assessed by HbA1c and fasting glucose levels improved in both
      groups, whereas insulin sensitivity index estimated by homeostasis model
      assessment (HOMA-R) decreased only in the troglitazone-treated group. Serum
      levels of hsCRP significantly decreased from 916+/-210 ng/ml to 569+/-123 ng/ml
      (P<0.05) in the troglitazone-treated group, whereas the levels remained unchanged
      in the metformin-treated group (from 1087+/-248 ng/ml to 1152+/-301 ng/ml). In
      the troglitazone-treated group, there was no difference in the absolute and
      percent change in serum hsCRP levels between responders, who displayed the
      decrease in HbA1c greater than 0.6% (n=12), and the remaining non-responders
      (n=7). The decrease in serum hsCRP concentrations was negatively related to
      baseline levels of serum hsCRP and insulin and HOMA-R. In conclusion,
      troglitazone, but not metformin, reduced serum hsCRP levels in type 2 diabetic
      patients. The decrease in serum hsCRP concentrations by troglitazone was
      associated with the pretreatment levels of hsCRP and insulin resistance, but
      independent of the changes in glycemia.

PMID- 14693410
TI  - Preference and resource utilization in elderly patients: InnoLet versus
      vial/syringe.
AB  - InnoLet is a disposable insulin injection device with a large easy-to-read dial,
      large push button for injection, and audible clicks for each unit injected. This
      clinical trial assessed patient preference, satisfaction, and utilization of
      healthcare resources (estimated nursing care) for InnoLet and vial/syringe.
      Patients with diabetes mellitus (N=79, mean age 68.2+/-8.6 years, duration of
      diabetes 16.5+/-10.9 years) having visual and/or motor disabilities and having
      difficulty (or required caregiver assistance) for previous injections by
      vial/syringe were randomized to use of either InnoLet or vial/syringe for 6
      weeks, then switched to the alternate regimen for 6 weeks. At the end of the
      study, utilization of healthcare resources was assessed in terms of the caregiver
      time required to assist in preparation, storage, and disposal of each device. For
      vial/syringe, 60% of patients required assistance in drawing up the appropriate
      dosage in the syringe, and 36% of patients required assistance when injecting
      insulin. A major portion of the patients (53%) could independently conduct
      injections (without nursing/caregiver assistance) during use of InnoLet, versus
      20% for vial/syringe. As a result, mean daily nursing costs associated with the
      injection regimen were US$ 114 for the InnoLet device, and US$ 196 for
      vial/syringe (P<0.001). A majority of patients (82%) indicated a preference for
      the InnoLet device (P<0.001).

PMID- 14693411
TI  - Growth hormone response to GHRH + GHRP-6 in type 2 diabetes during euglycemic and
      hyperglycemic clamp.
AB  - The aim of this study was to investigate the effect of two different glucose
      levels on GH response to the combined administration of GHRH+GHRP-6 in patients
      with type 2 diabetes. GH response to i.v. bolus of GHRH+GHRP-6 (100 mcg, each)
      was measured in 12 male patients with type 2 diabetes (mean age: 53.9+/-1.59
      years; BMI: 25.58+/-0.39 kg/m(2); mean HbA(1c): 8.7+/-0.42%), during a euglycemic
      (mean glucose: 4.92+/-0.08 mmol) hyperinsulinemic clamp (insulin infusion rate of
      100 mU/kg/h) and a hyperglycemic clamp (mean glucose: 12.19+/-0.11 mmol/l). There
      was no difference in basal GH levels between the hyperglycemic and euglycemic
      clamps (2.9+/-0.99 mU/l versus 1.48+/-0.44 mU/l; P>0.05). Peak GH response to
      GHRH+GHRP-6 during the hyperglycemic clamp was lower than in the englycemic clamp
      (112.45+/-14.45 mU/l versus 151.06+/-16.87 mU/l; P<0.05). Area under the GH curve
      was lower in the hyperglycemic than in the euglycemic clamp (6974.49+/-1001.95
      mU/l/min versus 9560.75+/-1140.65 mU/l/min; P<0.05). It is concluded that
      hyperglycemia significantly reduces GH response to combined administration of
      GHRH+GHRP-6 in normal weight patients with type 2 diabetes. It is suggested that
      ambient glucose levels should be taken into account during interpretation of GH
      response to combined administration of GHRH+GHRP-6 in patients with type 2
      diabetes.

PMID- 14693412
TI  - Polymorphisms in candidate genes for type 2 diabetes mellitus in a Mexican
      population with metabolic syndrome findings.
AB  - The metabolic or insulin resistance syndrome, characterized by hypertension,
      dyslipidemia, glucose intolerance and hyperinsulinemia, may have genetic
      determinants. The insulin gene (INS), insulin receptor gene (INSR) and insulin
      receptor substrate 1 gene (IRS1) have been proposed as candidate genes. We
      examined eight polymorphisms in these genes in 163 individuals from Yucatan,
      Mexico; this population has a high prevalence of obesity, type 2 diabetes
      mellitus and dyslipidemia. Subjects were evaluated for body mass index (BMI) and
      blood pressure. Blood samples were collected to determine glucose, insulin,
      triglycerides and cholesterol levels, as well as for DNA isolation. Restriction
      fragment length polymorphisms in INS, INSR and IRS1 were identified by polymerase
      chain reaction and digestion with selected restriction enzymes. Among the eight
      polymorphisms analyzed, the PstI polymorphism in INS was significantly associated
      with hypertriglyceridemia and with the presence of at least one abnormality
      related to the metabolic syndrome (P=0.007 and 0.004, respectively). The MaeIII
      polymorphism in INS was associated with fasting hyperinsulinemia (P=0.045). In
      multilocus analyses including both INS polymorphisms, significant associations
      were seen with hypertriglyceridemia (P=0.006), hypercholesterolemia (P=0.031) and
      with presence of at least one metabolic abnormality (P=0.009). None of the
      polymorphisms in INSR or IRS1 was associated with any of these traits. These
      findings suggest that the insulin gene may be an important determinant of
      metabolic syndrome, and particularly of dyslipidemia, in this population.

PMID- 14693413
TI  - Is acarbose equivalent to tolbutamide as first treatment for newly diagnosed type
      2 diabetes in general practice? A randomised controlled trial.
AB  - We performed a double blind randomised controlled trial in general practice to
      assess equivalence between tolbutamide and acarbose with respect to the effect on
      mean HbA(1c) in newly diagnosed patients with type 2 diabetes. Secondary
      objectives were to compare the effects of both treatments on fasting and post
      load blood glucose and insulin levels, lipids, and adverse events. Patients were
      randomised to receive acarbose, titrated step-wise to a maximum of 100mg three
      times daily (n=48) or tolbutamide, similarly titrated to a maximum of 2000 mg in
      three doses (n=48). The two treatments were considered equivalent if the two
      sided 90% confidence interval (CI) for the difference in mean HbA(1c) levels was
      within the range -0.4 to 0.4%. Results were analysed on an intention-to-treat,
      per-protocol and on worst-case basis. Both agents reduced the HbA(1c) percentage
      and fasting blood glucose levels. The difference in mean decrease of HbA(1c) was
      0.6% in favour of tolbutamide (90% CI 0.3, 0.9; 95% CI 0.2, 1.0). A worst-case
      analysis, assuming no change in HbA(1c) for dropouts, yielded a difference in
      mean decrease of 0.9% (90% CI 0.6, 1.2) in favour of tolbutamide. The difference
      in mean decrease of fasting blood glucose was 1.0 mmol/l in favour of tolbutamide
      (95% CI 0.3, 1.7). There were no significant differences in post-load blood
      glucose, fasting and post-load insulin levels, or lipids. In the acarbose group
      significantly more patients (15 versus 3) discontinued therapy because of adverse
      effects, mostly of gastrointestinal origin. We conclude that the results of this
      study favour tolbutamide over acarbose as first treatment for patients with newly
      diagnosed type 2 diabetes.

PMID- 14693414
TI  - Lifestyle change after gestational diabetes.
AB  - AIMS: Gestational diabetes mellitus (GDM) is a predictor for overt diabetes later
      in life. Thus, during pregnancy GDM patients are instructed to change lifestyle
      after pregnancy. The purpose of the present study was to assess the lifestyle
      changes made by these women. METHODS: The study was a mailed survey with
      structured questions on diet, weight loss, exercise and worry about developing
      diabetes. One hundred and twenty-one (79%) women agreed to participate 11-42
      months after pregnancy. Weight gain or loss was defined as a change >/=5 kg.
      RESULTS: Among women with body mass index (BMI) >25 kg/m(2), only 18% lost weight
      and more than 33% gained weight. In total, more women gained than lost weight
      (P<0.05). Prior to pregnancy, 90 (74%) women followed a diet rich in fat. In
      contrast, only 57 women (47%) did so at follow-up (P<0.001). Further analysis
      showed that among these 57 women, only 7% had lost weight since pregnancy
      compared to 25% of women eating healthy (P<0.05). Eighty-six percent were worried
      to some extent about the risk for subsequent diabetes. The exercise level did not
      change after pregnancy. Nineteen women (16%) had overt diabetes mellitus and 22
      (18%) impaired glucose tolerance (IGT) at follow-up. CONCLUSIONS: Although the
      majority of the women were concerned about developing overt diabetes, only a few
      had changed their lifestyle and/or lost weight after pregnancy. This indicates
      that lifestyle instruction needs to be much more frequent and intensive in the
      period after pregnancy in these women.

PMID- 14693415
TI  - Gestational diabetes: problems associated with the oral glucose tolerance test.

PMID- 14693416
TI  - CDK2 and cyclin E knockout mice: lessons from breast cancer.
AB  - The recent discovery that murine embryos can develop normally in spite of
      ablation of either CDK2 or cyclin E challenges the previously held dogma that
      cyclin E-CDK2 activity is strictly required for the cell-division cycle. However,
      genetic, cellular, biochemical and clinical evidence correlate aberrant cyclin E
      expression with tumorigenesis and poor patient prognosis, particularly in breast
      cancer. Thus cyclin E is a crucial regulator of estrogen-mediated growth
      signaling in breast tissue and, in spite of the apparent dispensability of cyclin
      E-CDK2 in development, the relationship between cyclin E and the development of
      breast cancer is convincing.

PMID- 14693420
TI  - Are XX and XY brain cells intrinsically different?
AB  - In mammals and birds, the sex of the gonads is determined by genes on the sex
      chromosomes. For example, the mammalian Y-linked gene Sry causes testis
      differentiation. The testes then secrete testosterone, which acts on the brain
      (often after conversion to estradiol) to cause masculine patterns of development.
      If this were the only reason for sex differences in neural development, then XX
      and XY brain cells would have to be deemed otherwise equivalent. This equivalence
      is doubtful because of recent experimental results demonstrating that some XX and
      XY tissues, including the brain, are sexually dimorphic even when they develop in
      a similar endocrine environment. Although X and Y genes probably influence brain
      phenotype in a sex-specific manner, much more information is needed to identify
      the magnitude and character of these effects.

PMID- 14693421
TI  - Prader-Willi syndrome: advances in genetics, pathophysiology and treatment.
AB  - Prader-Willi syndrome (PWS) is a complex human genetic disease that arises from
      lack of expression of paternally inherited imprinted genes on chromosome 15q11
      q13. Identification of the imprinting control centre, novel imprinted genes and
      distinct phenotypes in PWS patients and mouse models has increased interest in
      this human obesity syndrome. In this review I focus on: (i) the chromosomal
      region and candidate genes associated with PWS, and the possible links with
      individual PWS phenotypes identified using mouse models; (ii) the metabolic and
      hormonal phenotypes in PWS; (iii) postmortem studies of human PWS hypothalami;
      and (iv) current and potential advances in the management of PWS and its
      complications. This could have benefits for a wide spectrum of endocrine,
      paediatric and neuropsychiatric diseases.

PMID- 14693422
TI  - Salt-inducible kinase in steroidogenesis and adipogenesis.
AB  - The salt-inducible kinases (SIKs) are a family of related serine-threonine
      kinases. In cultured adrenocortical cells, SIK1 is rapidly but transiently
      induced by adrenocorticotropin (ACTH) treatment, suggesting that it contributes
      to ACTH-mediated induction of steroidogenic enzymes. However, ACTH treatment of
      Y1 mouse adrenocortical cells stimulates a rapid translocation of SIK1 from the
      nucleus to the cytoplasm, and SIK1 represses the transcription of a steroidogenic
      enzyme by inhibiting the action of cAMP-responsive elements in the promoter.
      These studies suggest that SIK1 has a role in the fine tuning of steroidogenic
      enzyme production during the initial phase of steroidogenesis. SIK2 is found in
      adipocytes and phosphorylates a specific serine residue in insulin receptor
      substrate-1. This finding, along with the fact that its expression is raised in
      the white adipose tissue of mice with type 2 diabetes mellitus, suggests that
      SIK2 might be involved in metabolic regulation in adipose tissue. Thus, members
      of the SIK family are emerging as important modulators of key processes such as
      steroid hormone biosynthesis by the adrenal cortex and insulin signaling in
      adipocytes.

PMID- 14693423
TI  - GLP-1 inhibition of pancreatic islet cell apoptosis.
AB  - Apoptosis plays an important role in the normal physiology of the pancreas, the
      pathogenesis of diabetes mellitus (DM) and the success rate of islet
      transplantation. Glucagon-like peptide-1 (GLP-1), an incretin hormone with
      multiple effects on glucose metabolism and pancreatic gene expression, has
      recently been found to have antiapoptotic properties. This new property of GLP-1
      has clinical relevance for the treatment of patients with overt DM, possible
      prevention of DM during the stage of impaired glucose tolerance and improvement
      in the outcome of islet transplantation. The pleiotropic effects of GLP-1 have
      fostered considerable interest in evaluating the efficacy of GLP-1, and might
      lead in the near future to its use in the prevention and/or treatment of DM.

PMID- 14693424
TI  - The nuclear pore complex: disease associations and functional correlations.
AB  - Nuclear pore complexes (NPCs) are large protein structures spanning the double
      membrane of the eukaryotic nucleus that serve as sites for translocation of
      macromolecules between the nucleus and the cytoplasm. The vertebrate NPC has
      recently been found to comprise approximately 30 distinct proteins, collectively
      referred to as nucleoporins. Studies over the past several years have
      demonstrated that individual nucleoporins have unique roles in regulating NPC
      function and the nucleocytoplasmic transport of proteins and RNAs. The unique
      functions of individual nucleoporins have been made most clear through their
      associations with specific human diseases. Here, we highlight the relationships
      between individual nucleoporins and disease, with particular emphasis given to
      ALADIN, a nucleoporin linked to a genetically heritable human disease known as
      triple A syndrome.

PMID- 14693425
TI  - Activation of the human GH gene cluster: roles for targeted chromatin
      modification.
AB  - The cluster of genes encoding the human growth hormone (GH) contains an array of
      five highly related genes. From 5' to 3' these are: GHN, CSL (encoding chorionic
      somatomammotropin-like gene), CSA, GHV (encoding GH-variant gene) and CSB. These
      five genes are expressed in mutually exclusive tissue distributions, GHN in
      pituitary somatotropes and the remaining four genes in placental villous
      syncytiotrophoblasts. The onset of GH expression during development is dependent
      upon epigenetic modifications at the GH locus under the control of its distal
      locus control region (LCR). A clear understanding of these normal epigenetic
      controls on the expression of GH could lead to new insights into the development
      and treatment of isolated GH deficiency in children. This review focuses on the
      role of the LCR in histone hyperacetylation at the GH locus and subsequent
      effects on the tissue-specific activation of these genes.

PMID- 14693433
TI  - Chemiluminescence detection systems for the analysis of explosives.
AB  - The objective of this paper is to provide a comprehensive review of explosive
      detection by chemiluminescence (CL) through a summary of the relevant literature
      in the last 5 years and a synopsis of current research topics and developments.
      The literature reviewed is specially addressed for the detection of a group of
      high explosives, containing nitrogen compounds. Most explosives compounds contain
      either nitro or nitrate groups which make possible their detection and
      quantification using detection systems based on chemiluminescent reactions.
      Practical considerations and experimental requirements are indicated, and the
      possibilities and limitations are evaluated.

PMID- 14693434
TI  - Hydrocode simulations of air and water shocks for facility vulnerability
      assessments.
AB  - Hydrocodes are widely used in the study of explosive systems but their use in
      routine facility vulnerability assessments has been limited due to the
      computational resources typically required. These requirements are due to the
      fact that the majority of hydrocodes have been developed primarily for the
      simulation of weapon-scale phenomena. It is not practical to use these same
      numerical frameworks on the large domains found in facility vulnerability
      studies. Here, a hydrocode formulated specifically for facility vulnerability
      assessments is reviewed. Techniques used to accurately represent the explosive
      source while maintaining computational efficiency are described. Submodels for
      addressing other issues found in typical terrorist attack scenarios are
      presented. In terrorist attack scenarios, loads produced by shocks play an
      important role in vulnerability. Due to the difference in the material properties
      of water and air and interface phenomena, there exists significant contrast in
      wave propagation phenomena in these two medium. These physical variations also
      require special attention be paid to the mathematical and numerical models used
      in the hydrocodes. Simulations for a variety of air and water shock scenarios are
      presented to validate the computational models used in the hydrocode and
      highlight the phenomenological issues.

PMID- 14693435
TI  - Preparation of polyelectrolytes for wastewater treatment.
AB  - Liquid-phase polymerisation of acrylamide-acrylic acid to form polyelectrolytes
      used in wastewater cleaning was examined using accelerated electron beam and
      microwave irradiation methods. Polymerisation was carried out in aqueous
      solutions at temperatures approximately 60 degrees C. Monomers total
      concentration was established at 40% (36% acrylamide and 4% acrylic acid). Only
      using the features of simultaneous radiation-induction and microwave heating can
      result in the formation of linear polymer chains with good water solubility and
      low residual monomer concentration. The flocculation capacity of the obtained
      polymers was tested using two wastewaters, one sampled from a slaughterhouse and
      the other from a vegetable oil plant. Quality indicators such as total suspended
      matters (TSM), chemical oxygen demand (COD), biological oxygen demand (BOD) and
      fat, oils and grease (FOG) were measured before and after the treatment with
      polymeric flocculants and compared with the results obtained in classical
      treatment with Al(2)(SO(4))(3). It was found that the combined treatment with
      polymers and Al(2)(SO(4))(3) increases the degree of purification of both
      wastewaters up to 99%.

PMID- 14693436
TI  - Prospects for cleaning ash in the acidic effluent from bioleaching of sulfidic
      concentrates.
AB  - Leaching of ashes in sulfuric acid (pH 1.0, liquid-to-solid (L/S) ratio 10:1, 25
      degrees C) has been characterized with respect to the neutralizing capacity and
      the dissolution of dominant ions and trace elements. The conditions mimic the
      oxidation stage of a biohydrometallurgical process for base metal production from
      sulfidic mineral concentrates. Direct acid leaching of ash, integrated with this
      metallurgical process, offers a feasible route to the sustainable handling of
      metal-rich ashes. The treated ash will be deposited together with the inert
      mineral residue. Cd, Co, Cu, Ni and Zn are effectively leached and can be
      recovered utilizing existing hydrometallurgical technology, but the recovery of
      other readily dissolved metals, notably Mn, U and V, requires that additional
      steps are implemented. We make two recommendations for industrial processes. The
      first is to replace limestone with ash from biofuels, except peat, for pH control
      in biohydrometallurgical processing. This requires a modest increase of fresh
      alkali compared with limestone. The second is to implement sulfuric acid leaching
      of fly ash from the combustion of solid waste and other metal-rich fuels (used
      wood, tires), thereby avoiding costly ash-deposits. There is a significant
      economic incentive for these changes, since no costly ash-deposits and less
      limestone will be needed.

PMID- 14693437
TI  - A kinetic model of aqueous-phase alkali hydrolysis of 2,4,6-trinitrotoluene.
AB  - Alkali hydrolysis of 2,4,6-trinitrotoluene (TNT) was studied using batch
      experiments with starting pH values 11 and 12 in glass conical flasks covered
      with aluminum foil. Isothermal (25 and 40 degrees C) as well as non-isothermal
      experiments were conducted. Experiments starting at pH 12 resulted in >95%
      reduction in the concentration of TNT; those starting at pH 11 had a maximum
      reduction of 20-25% in TNT concentration. In all the experiments, one major
      stable intermediate was produced but it could not be identified. The experimental
      data were used to determine the overall stoichiometry of TNT and hydroxyl ions.
      Approximately 100 M (standard deviation 11.4) of hydroxyl ions were consistently
      consumed per mole of TNT. However, control experiments showed that all but 13 M
      (standard deviation 2) of hydroxyl ions were consumed in reactions not related to
      TNT. A simple kinetic model involving formation of the intermediate was proposed
      to account for changes in concentrations of TNT and hydroxyl ions. The rate
      constants and activation energies of the reactions were identified using
      isothermal data and the kinetic model was then used to predict the experimental
      data in the non-isothermal experiments reasonably well.

PMID- 14693438
TI  - Adsorption characteristics of Fe(III) and Fe(III)-NTA complex on granular
      activated carbon.
AB  - The adsorption of Fe(3+) ion on granular activated carbon has been studied in
      kinetic and equilibrium conditions taking into account the adsorbate
      concentration, temperature and solution pH as major influential factors. In
      addition, the effect of nitrilotriacetic acid on adsorption reaction as a
      complexing agent has been examined. Kinetic studies showed that the adsorption
      rate was increased as the initial Fe(3+) concentration was raised. The adsorption
      reaction was estimated to be first-order at room temperature. The adsorption rate
      and equilibrium adsorption of Fe(3+) increased as the temperature rose. The
      activation energy for adsorption was approximately 2.23 kJ mol(-1), which implied
      that Fe(3+) mainly physically adsorbed on activated carbon. Coexistence of
      nitrilotriacetic acid with Fe(3+) resulted in a decrease of equilibrium
      adsorption and the extent of decrease was proportional to the concentration of
      nitrilotriacetic acid. In the presence of nitrilotriacetic acid, the
      adsorbability of Fe(3+) decreased with pH. However, the trend was reversed in the
      absence of nitrilotriacetic acid. When activated carbon was swelled by acetic
      acid, the specific surface area was increased and maximum swelling was achieved
      at approximately 48 h of swelling time. Thermodynamic parameters such as
      DeltaG(o), DeltaH(o) and DeltaS(o) for adsorption reaction were estimated based
      on equilibrium data and in connection with these results the thermodynamic
      aspects of adsorption reaction were discussed.

PMID- 14693439
TI  - Groundwater quality in some villages of Haryana, India: focus on fluoride and
      fluorosis.
AB  - The fluoride concentration in underground water was determined in four villages
      of Jind district of Haryana state (India) where it is the only source of drinking
      water. Various other water quality parameters such as pH, electrical
      conductivity, total dissolved salts, total hardness, total alkalinity as well as
      sodium, potassium, calcium, magnesium, carbonate, bicarbonate, chloride and
      sulfate concentrations were also measured. A systematic calculation of
      correlation coefficients among different physico-chemical parameters was
      performed. The analytical results indicated considerable variations among the
      analyzed samples with respect to their chemical composition. Majority of the
      samples do not comply with Indian as well as WHO standards for most of the water
      quality parameters measured. The fluoride concentration in the underground water
      of these villages varied from 0.3 to 6.9 mg/l, causing dental fluorosis among
      people especially children of these villages. Overall water quality was found
      unsatisfactory for drinking purposes without any prior treatment except at eight
      locations out of 60.

PMID- 14693443
TI  - Use of poly(lactic acid) amendments to promote the bacterial fixation of metals
      in zinc smelter tailings.
AB  - The ability of poly(lactic acid) (PLA) to serve as a long-term source of lactic
      acid for bacterial sulfate reduction activity in zinc smelter tailings was
      investigated. Solid PLA polymers mixed in water hydrolyzed abiotically to release
      lactic acid into solution over an extended period of time. The addition of both
      PLA and gypsum was required for indigenous bacteria to lower redox potential,
      raise pH, and stimulate sulfate reduction activity in highly oxidized smelter
      tailings after one year of treatment. Bioavailable cadmium, copper, lead and zinc
      were all lowered significantly in PLA/gypsum treated soil, but PLA amendments
      alone increased the bioavailability of lead, nickel and zinc. Similar PLA
      amendments may be useful in constructed wetlands and reactive barrier walls for
      the passive treatment of mine drainage, where enhanced rates of bacterial sulfate
      reduction are desirable.

PMID- 14693444
TI  - Advanced bioconversion of biowaste for production of a peat substitute and
      renewable energy.
AB  - Traditional composting systems for biowaste generally produce low quality
      composts that may endanger recycling. A pilot-scale bioconversion process
      yielding quality compost and renewable energy was designed and tested. The
      process consisted of a set of wet physical separation units, composting and
      anaerobic digestion. Biowaste was divided in four streams by physical separation:
      (1) organic fraction >2 mm, (2) inorganic fraction 0.05-2 mm, (3) residual
      fraction composed of organics 0.05-2 mm and the fraction <0.05 mm and (4) a
      fraction solubilised in the washing water. The organic fraction >2 mm was
      composted and the compost, high in organic matter and low in EC and heavy metals,
      aimed at replacing peat in horticulture. The inorganic fraction 0.05-2 mm was
      completely made up of sand and can be used as a construction material.
      Solubilised organic matter in the washing water was converted to CH(4) by
      anaerobic digestion. The residual fraction can be used as landfill cover
      material.

PMID- 14693445
TI  - Chlorophyll production from Spirulina platensis: cultivation with urea addition
      by fed-batch process.
AB  - The cyanobacterium Spirulina platensis is an attractive alternative source of the
      pigment chlorophyll, which is used as a natural color in food, cosmetic, and
      pharmaceutical products. In this work, the influence of the light intensity and
      urea supplementation as a nitrogen source using fed-batch cultivation for S.
      platensis growth and chlorophyll content was examined. Cultivations were carried
      out in 5 l open tanks, at 30+/-1 degrees C. Response surface methodology was
      utilized for analysis of the results, and models were obtained for biomass
      productivity, nitrogen-cell conversion factor and chlorophyll productivity. The
      best cellular growth was observed with 500 mg/l of urea at a light intensity of
      5600 lx, whereas the highest concentration of chlorophyll in the biomass was
      observed with 500 mg/l of urea at a light intensity of 1400 lx. Overall, the best
      chlorophyll productivity was observed with 500 mg/l of urea at a light intensity
      of 3500 lx, providing the optimal balance between the cellular growth and the
      biomass chlorophyll content.

PMID- 14693446
TI  - Aerobic degradation of the azo dye acid red 151 in a sequencing batch biofilter.
AB  - The azo dye acid red 151 (AR151) was aerobically biodegraded in a sequencing
      batch biofilter packed with a porous volcanic rock. AR151 was used as the sole
      source of carbon and energy for acclimated microorganisms. Acclimation was
      followed using the degradation time and the oxygen uptake rate. A maximal oxygen
      uptake rate of 0.5 mg O(2)/(lmin) was obtained. Mineralization studies showed
      that 73% (as carbon) of the initial azo dye was transformed to CO(2) by the
      consortia. A maximal substrate degradation rate of 247 mg AR151/(l(reactor)d) was
      obtained. Color removal was up to 99% using an initial concentration of 50 mg
      AR151/l. Anaerobic tests suggested that in the interior of the porous material,
      anaerobic biotransformations can occur, contributing from 14% to 16% of the
      decoloration of the azo dye.

PMID- 14693447
TI  - Removal of chromium by mucilaginous seeds of Ocimum basilicum.
AB  - Polysaccharides bound to bacteria or in isolated form have been shown to bind
      heavy metals. A limitation of this technology can be overcome by immobilization.
      In view of this Ocimum basilicum seeds which swell upon wetting could serve as
      natural immobilized source of agriculturally-based polysaccharides. The seeds
      consist of an inner hard core and a pectinous fibrillar outer layer. Pretreating
      the seeds with acid, alkali, periodate or boiling in water was found to alter the
      metal binding capacity. Of the various treatments given, seeds boiled in water
      were found to be superior in terms of mechanical stability and exhibited fairly
      optimal Cr(VI) uptake kinetics. The maximum adsorption capacity as calculated
      from the Langmuir isotherm was 205 mg Cr/g dry seeds. Biosorption of Cr(VI) was
      found to be pH dependent with maximum uptake at pH 1.5 wherein sorption was not
      affected by the presence of other metal ions such as Cd(2+), Cu(2+), Ca(2+) and
      Na(+). Seeds were used in a packed bed reactor for the continuous removal of
      Cr(VI). Thus O. basilicum seeds may have application as a potential bioresource
      in tropical countries such as India where they are widely available.

PMID- 14693448
TI  - Rice bran stabilization and rice bran oil extraction using ohmic heating.
AB  - Ohmic heating has been shown to increase the extraction yields of sucrose from
      sugar beets, apple juice from apples, beet dye from beet root, and soymilk from
      soybeans. Rice bran is a byproduct of the rice milling process that has economic
      potential by virtue of highly nutritious rice bran oil contained within the bran.
      In this study, ohmic heating was used to stabilize rice bran and to improve rice
      bran oil extraction yield as compared to microwave heating and a control (no
      heating). Results showed that ohmic heating is an effective method for rice bran
      stabilization with moisture addition. Free fatty acid concentration increased
      more slowly than the control for raw bran samples subjected to ohmic heating with
      no corresponding temperature rise, indicating that electricity has a non-thermal
      effect on lipase activity. Ohmic heating increased the total percent of lipids
      extracted from rice bran to a maximum of 92%, while 53% of total lipids were
      extracted from the control samples. Lowering the frequency of alternating current
      significantly increased the amount of oil extracted, probably due to
      electroporation. Ohmic heating was successfully applied to rice bran despite its
      high oil content. This could have important implications for the enhanced
      extraction of non-polar constituents.

PMID- 14693449
TI  - Xylose fermentation by genetically modified Saccharomyces cerevisiae 259ST in
      spent sulfite liquor.
AB  - Spent sulfite pulping liquor (SSL) is a high-organic content byproduct of acid
      bisulfite pulp manufacture which is fermented to make industrial ethanol. SSL is
      typically concentrated to 240 g/l (22% w/w) total solids prior to fermentation,
      and contains up to 24 g/l xylose and 30 g/l hexose sugars, depending upon the
      wood species used. The xylose present in SSL is difficult to ferment using
      natural xylose-fermenting yeast strains due to the presence of inhibitory
      compounds, such as organic acids. Using sequential batch shake flask experiments,
      Saccharomyces cerevisiae 259ST, which had been genetically modified to ferment
      xylose, was compared with the parent strain, 259A, and an SSL adapted strain, T2,
      for ethanol production during SSL fermentation. With an initial SSL pH of 6,
      without nutrient addition or SSL pretreatment, the ethanol yield ranged from 0.32
      to 0.42 g ethanol/g total sugar for 259ST, compared to 0.15-0.32 g ethanol/g
      total sugar for non-xylose fermenting strains. For most fermentations, minimal
      amounts of xylitol (<1 g/l) were produced, and glycerol yields were approximately
      0.12 g glycerol/g sugar consumed. By using 259ST for SSL fermentation up to 130%
      more ethanol can be produced compared to fermentations using non-xylose
      fermenting yeast.

PMID- 14693450
TI  - Performance of subsurface flow constructed wetland taking pretreated swine
      effluent under heavy loads.
AB  - Subsurface flow constructed wetlands (SSFCW) subjected to changing of loading
      rates are poorly understood, especially when used to treat swine waste under
      heavy loads. This study employed a SSFCW system to take pretreated swine effluent
      at three hydraulic retention times (HRT): 8.5-day HRT (Phase I), 4.3-day HRT
      (Phase II), and 14.7-day HRT (Phase III). Results showed that the system
      responded well to the changing hydraulic loads in removing suspended solids (SS)
      and carbonaceous oxygen demands. The averaged reduction efficiencies for four
      major constituents in the three phases were: SS 96-99%, chemical oxygen demand
      (COD) 77-84%, total phosphorus 47-59%, and total nitrogen (TN) 10-24%. While
      physical mechanisms were dominant in removing pollutants, the contributions of
      microbial mechanisms increased with the duration of wetland use, achieving 48% of
      COD removed and 16% of TN removed in the last phase. Water hyacinth made only a
      minimal contribution to the removal of nutrients. This study suggested that the
      effluent from SSFCW was appropriate for further treatment in land applications
      for nutrient assimilation.

PMID- 14693451
TI  - The fuel properties of pyrolysis liquid derived from urban solid wastes in
      Bangladesh.
AB  - Urban solid wastes in the form of scrap tyre, waste plastic and waste paper, were
      pyrolyzed in an externally heated fixed bed reactor. The condensed liquids were
      analyzed for their properties as fuels and compared with petroleum-derived
      products. The properties were physical properties, higher heating value,
      elemental (CHNOS) analysis and chemical composition using Fourier transform infra
      red (FTIR) spectroscopy. The results showed that the pyrolysis of urban solid
      wastes may be a potential source of liquid hydrocarbon fuel.

PMID- 14693452
TI  - Investigations into the pyrolytic behaviour of coal/biomass blends using
      thermogravimetric analysis.
AB  - Investigations into the pyrolytic behaviour during co-pyrolysis of coal, biomass
      materials and coal/biomass blends prepared at different ratios (10:90, 20:80,
      30:70 and 50:50) have been conducted using a thermogravimetric analysis (TGA)
      apparatus. The coal sample selected was Collie sub-bituminous coal from Western
      Australia, while wood waste (WW) and wheat straw (WS) were used as biomass
      samples. Three thermal events were identified during the pyrolysis. The first two
      were dominated by the biomass pyrolysis, while the third was linked to the coal
      pyrolysis, which occurred at much higher temperatures. No interactions were seen
      between the coal and biomass during co-pyrolysis. The pyrolytic characteristics
      of the blends followed those of the parent fuels in an additive manner. Among the
      tested blends, 20:80 blends showed the lowest activation energies of 90.9 and
      78.7 kJmol(-1) for coal/WW and coal/WS blends respectively. The optimum blend
      ratio for pyrolysis of coal/WS was 50:50 with a high degradation rate in all the
      thermal events and a higher mass loss over the course of the co-pyrolysis
      compared to coal/WW blends examined. The reaction orders in these experiments
      were in the range of 0.21-1.60, thus having a significant effect on the overall
      reaction rate. Besides the pyrolysis of coal alone, the 50:50 coal/biomass blends
      had the highest reaction rate, ranging 1x10(9)-2x10(9) min(-1). The experimental
      results may provide useful data for power generation industries for the
      development of co-firing options with biomass.

PMID- 14693453
TI  - Heavy metal adsorption properties of a submerged aquatic plant (Ceratophyllum
      demersum).
AB  - Heavy metals can be adsorbed by living or non-living biomass. Submerged aquatic
      plants can be used for the removal of heavy metals. In this paper, lead, zinc,
      and copper adsorption properties of Ceratophyllum demersum (Coontail or hornwort)
      were investigated and results were compared with other aquatic submerged plants.
      Data obtained from the initial adsorption studies indicated that C. demersum was
      capable of removing lead, zinc, and copper from solution. The metal biosorption
      was fast and equilibrium was attained within 20 min. Data obtained from further
      batch studies conformed well to the Langmuir Model. Maximum adsorption capacities
      (q(max)) onto C. demersum were 6.17 mg/g for Cu(II), 13.98 mg/g for Zn(II) and
      44.8 mg/g for Pb(II). Kinetics of adsorption of zinc, lead and copper were
      analysed and rate constants were derived for each metal. It was found that the
      overall adsorption process was best described by pseudo second-order kinetics.
      The results showed that this submerged aquatic plant C. demersum can be
      successfully used for heavy metal removal under dilute metal concentration.

PMID- 14693454
TI  - Recovery of phenolic antioxidants from wine industry by-products.
AB  - The recovery process of the phenolic compounds contained in the wine industry by
      products and their antioxidant activity were examined in this work. To this
      purpose, a combined process of liquid and supercritical solvent extraction was
      employed. At first the effect of various process parameters of the liquid solvent
      extraction--the type of solvent and the pretreatment of the raw material
      (composition (skins, seeds, stems) and crushing)--on the antioxidant activity of
      the extract was examined. It was shown that an extract of a higher antioxidant
      activity was obtained by using ethyl acetate as solvent and raw material free of
      stems. These extracts were further treated with supercritical carbon dioxide (SC
      CO(2)) at various extraction pressures, which resulted in their significant
      enrichment in phenolic compounds and the improvement of their antioxidant and
      organoleptic properties, especially at pressures higher than 100 bar. The
      antioxidant activity of the products was determined by using the Rancimat method,
      as well as a simple and not time-consuming free radical method. It was proved
      that both the ethyl acetate extracts and those treated with SC CO(2) had
      antioxidant activity comparable to that of antioxidants commonly used in
      industry, that is butylhydroxytoluene (BHT), a synthetic antioxidant, and
      Rosemary extract, a widely known natural one.

PMID- 14693455
TI  - Influence of environmental and nutritional factors in the production of
      astaxanthin from Haematococcus pluvialis.
AB  - Astaxanthin extracted from green algae is desirable in the food and
      pharmaceutical industries due to its antioxidant properties. The green
      unicellular clear water microalga Haematococcus pluvialis has a high production
      rate of astaxanthin; indeed, it contains more than 80% astaxanthin content in its
      cells. This remarkable astaxanthin production is commonly obtained under stress
      conditions such as nutrient deficiency (N or P), high NaCl concentrations,
      variations of temperature, and other factors. In this vein, a great research
      effort has been oriented to determine optimal conditions for astaxanthin
      production by H. pluvialis. The objective of the present study was the analysis
      of environmental factors, such as light intensity, aeration and nutrients on the
      growth and astaxanthin production of H. pluvialis. Maximum growth of H. pluvialis
      obtained was 3.5x10(5) cells/ml in BBM medium at 28 degrees C under continuous
      illumination (177 micromol photon m(-2)s(-1)) of white fluorescent light, with
      continuous aeration (1.5 v.v.m.). Meanwhile, maximal astaxanthin production was
      98 mg/g biomass in BAR medium with continuous illumination (345 micromol photon
      m(-2)s(-1)), with 1 g/l of sodium acetate and without aeration.

PMID- 14693456
TI  - Decomposition of kitchen waste amended with cow manure using an epigeic species
      (Eisenia fetida) and an anecic species (Lampito mauritii).
AB  - An epigeic (surface dweller) earthworm species Eisenia fetida and an anecic (deep
      burrower) earthworm species Lampito mauritii have been tested for decomposition
      of kitchen waste plus cow dung. Chemical analyses of worm-worked substrates by
      both species showed g/kg increases in nitrogen, phosphorus and potassium and
      decreases in C/N and C/P ratios after 150 days of vermicomposting. However,
      organic carbon matter showed reduction in their amounts for 3-4 months and
      afterwards slightly increased up to 150 days. E. fetida produced 0.27%, 156%, 41%
      and 38% increases in organic carbon, nitrogen, phosphorus, and potassium as well
      as 61% and 29% decreases in C/N and C/P ratios as compared to control after 150
      days of earthworm inoculation. In contrast, L. mauritii produced 14%, 102%, 33%
      and 42% increases in organic carbon, nitrogen, phosphorus and potassium as well
      as 43% and 14% decreases in C/N and C/P ratios as compared to control after 150
      days of earthworm activity. There was moderate mineralization and faster
      decomposition by E. fetida in comparison to moderate mineralization and moderate
      decomposition by L. mauritii. The average numbers of cocoons and adults produced
      were greater by E. fetida than by L. mauritii after 150 days. These results
      indicate E. fetida may be a better adapted species for decomposition of kitchen
      waste plus cow dung under tropical conditions.

PMID- 14693457
TI  - New compound fires up pain research.

PMID- 14693459
TI  - Inflammatory clues to drug toxicity.

PMID- 14693462
TI  - Pill-punching patents.

PMID- 14693463
TI  - A model for NF-kappa B regulation by GSK-3 beta.

PMID- 14693464
TI  - Probiotics: time to move beyond Metchnikoff?

PMID- 14693465
TI  - Drug discovery and development for metabolic diseases.

PMID- 14693466
TI  - Rediscovering the sweet spot in drug discovery.
AB  - Advances over the past decade in drug discovery technologies have not yet led to
      an increase in productivity. We analyzed the reasons that have led to this
      juncture and identify the selection of the right target and the right lead as
      crucial. New approaches are required to take full advantage of the genomics
      revolution. For targets, methods are becoming available for high-throughput
      proteome analysis and pathway characterization that synergize with studies of
      disease association and differential expression. For leads, methods are being
      developed that 'reverse' the high-throughput screening paradigm by mapping drugs
      and drug-like compounds back onto the proteome. The synergy between pathway
      mapping and compound mapping could allow the pharmaceutical and biotechnology
      industries to rediscover the sweet spot of research productivity.

PMID- 14693467
TI  - Mining the microbial metabolome: a new frontier for natural product lead
      discovery.
AB  - Traditionally, natural products have been important sources of new leads for the
      pharmaceutical industry, but with discovery rates of novel structural classes in
      decline, the need to bioprospect alternate sources of chemical diversity is
      evident. Microbial genome sequencing projects have revealed the presence of
      'silent' biosynthetic gene clusters where there is no current detectable product.
      Likewise, culture-independent techniques have provided access to the collective
      genomes of environmental microflora. Both sources of molecular diversity could
      encode potentially valuable metabolites. The ability to measure the entire
      complement of metabolites within microorganisms that are used as surrogate hosts
      to express such gene clusters will be crucial to the exploitation of these yet
      untapped reservoirs of metabolic diversity for future natural product drug
      discovery.

PMID- 14693468
TI  - Confocal optics microscopy for biochemical and cellular high-throughput
      screening.
AB  - In recent years, both academia and pharmaceutical industry have produced
      significant advances in confocal detection and spectroscopy by laser-induced
      fluorescence. Confocal fluorescence studies provide information on identity,
      size, diffusion coefficient and concentration of the fluorescently labeled
      entity. This enables the establishment of sophisticated biochemical drug
      screening assays using the multitude of fluorescence parameters that can be
      observed (e.g. molecular brightness, fluorescence lifetime, anisotropy, resonance
      energy transfer). In cellular screening assays, confocality introduces spatial
      resolution in the vertical direction and reduces background fluorescence from
      outside the focal plane. Confocal HTS systems focusing on femtoliter-sized
      observation volumes allow for assay volumes far beyond current limits.

PMID- 14693471
TI  - [The French health aid policy].

PMID- 14693472
TI  - [Ketoacidosis in children and teenagers in Congo].
AB  - Diabetes mellitus is frequent in African children and adolescents. Its treatment
      faces some problems and complications. Ketoacidosis is among the main
      complications and its prognosis is bad. This retrospective study reports 93 cases
      of young patients observed over 10 years. It aims at presenting the
      characteristics of ketoacidosis in Brazzaville. The results of this study have
      reported ketoacidosis in 79.3% of the cases. Stopping the treatment (48.1%) and
      infections (28.6%) were the main factors. In 18.3% of the cases, the disease
      started by ketoacidosis. Despite the high mortality rate (18.2%), a favourable
      evolution was observed in 83.3% of the cases. It is the first cause of death in
      children suffering Diabetes mellitus in the Department for diabetes mellitus and
      endocrine diseases at Brazzaville University Hospital. Health education of both
      parents and children, a qualified personnel should help reduce the frequency of
      this complication.

PMID- 14693473
TI  - [Antibiotherapy in osteoarticular infections in children suffering from
      hemoglobinopathy in the University Teaching Hospital of Yopougon].
AB  - OBJECTIVE: The objective of this work was to evaluate antibiotherapy in osteo
      articular infections found in children with henioglobinopathy, by identifying the
      antibiotics used and their mode of action. Their cost and efficacy were also
      assessed. MATERIALS AND METHOD: The study was retrospective and it took place in
      the haematology unit, the paediatric surgical department and the central pharmacy
      of the University Teaching Hospital of Yopougon from 1991 through 1998. Thirty
      two medical records of children, carriers of osteo-articular infections (OAI),
      were selected. Amongst these patients, most of whom had sickle-cell anaemia
      (97%), 50% were homozygous. Osteomyelitis represented 78% of these infections
      (salmonella infections being the most frequent cause, amounting to 35%). RESULTS:
      Fifteen types of antibiotics amongst 57 from 5 families of drugs were used, with
      biotherapy (association of two drugs) being used in 69% of cases. The association
      of pefloxacine and netilmicine was the most frequently used and it was found to
      be the most expensive. The treatment was judged efficacious, with a satisfactory
      result in 75% of cases, based on the clinical criteria. DISCUSSION: Bitherapy is
      the type of treatment, which is often of concern to many authors and relies on
      the general consensus surrounding the most likely emergency treatment of osteo
      articular infections. Certain particularities are worth mentioning regarding this
      utilisation: the multiplicity of the molecules due to frequent rupture of
      hospital stock; the use of fluoroquinolones exceptionally prescribed in children
      under 15. CONCLUSION: This antibiotherapy is justified owing to its efficacy on a
      sensitive issue concerning a pathology with grave sequellae, where long-term
      monitoring is necessary.

PMID- 14693474
TI  - [Penicillium marneffei infection and AIDS. A review of 12 cases reported in the
      Tropical Diseases Centre, Ho Chi Minh City (Vietnam)].
AB  - Penicillium marneffei is a thermal dimorphic fungus which is endemic in an
      ecologic niche restricted to the Far East and which may cause deep-seated
      infection in humans and rodents. Discovered in the late 1950s from the bamboo rat
      Rhizomys sinensis, in Vietnam, P. marneffei was initially identified in HIV
      infected individuals. A disseminated and progressive infection, it is the third
      most common opportunistic morbidity in the late course of HIV infection. We
      report the clinical and therapeutic features of a series of 12 HIV-infected
      adults with disseminated P. marneffei infection in Vietnam. From May to
      September, 2001, 12 patients with P. marneffei infection confirmed by culture
      were identified among 273 HIV-infected patients studied at the Tropical Diseases
      Centre, Ho Chi Minh City, Vietnam. The clinical signs were related to the
      reticuloendothelial system involvement. Common clinical features included fever,
      cutaneous manifestations, lymphadenopathy, hepatomegaly, splenomegaly, and marked
      anemia. The organism was identified from skin specimens or blood culture. Cases
      were consistently found with low CD4 (+) cell count. Treatment with parenteral
      amphotericin B and itraconazole was relatively effective, although treatment with
      a delaying diagnosis remained associated with pejorative prognosis.

PMID- 14693475
TI  - [Neurologic disturbances in human immunodeficiency virus carriers in Yaounde].
AB  - Neurological manifestations are frequent with the acquired immunodeficiency
      syndrome (AIDS). They can be seen at the onset of the illness but more often they
      are found during its terminal phase. The aim of this study is to describe the
      neurological complications observed in AIDS as well as the evolution in the
      intensive care unit of the Yaounde General Hospital, Republic of Cameroon. This
      prospective study was carried out during a two-year period at the intensive care
      unit. All patients who were HIV-positive and who presented a neurological
      disorder diagnosed during the interrogation and clinical examination were
      included in this study. In these patients, the following paraclinical
      examinations were performed: ocular fundi, CD4 lymphocytes titre, toxoplasmosis
      serology, lumbar tap, and cerebral scan. A diagnosis was made and the patients
      were treated accordingly. The appreciation of the evolution was done in relation
      with the clinical state and the mortality observed in the service. We recruited
      51 patients in all, aged 38 years on average (+/- 7 years). There were 31 women
      and 20 men. The neurological disorders observed were 26 states of coma, 14
      agitations with mental confusion, 6 meningitis syndromes, 5 hallucinations. The
      titre of CD4 showed an average of 146/mm3 (+/- 12). Toxoplasmosis serology was
      positive for 6 patients. The cerebrospinal fluid revealed 2 cases of purulent
      meningitis. The ocular fundi showed 5 cases of papillary oedema. The cerebral
      scan showed 8 cases of cerebral abscess, 4 cases of cerebral tumour and 6 cases
      of cerebral toxoplasmosis. These paraclinical findings have enabled us to
      establish the following classification of the patients: cerebral tumors (n=4);
      bacterial meningitis (n=2); aseptic meningitis (n=10); cerebral toxoplasmosis
      (n=6); sub-acute encephalopathy (n=21); cerebral abscess (n=8). These patients
      were treated according to the diagnosis. The clinical evolution was marked by
      recovery in 14 patients with improved clinical state and by mortality in 34
      patients. Many neurological disorders exist in HIV infections. These
      complications vary according to the stage of the illness. They are caused either
      by opportunistic infections, by tumours or by the virus itself. The most frequent
      complication in our service is sub-acute encephalitis, which induces coma. This
      is due to the fact that the intensive care unit receives terminal patients coming
      from other services. This late recruitment of patients also explains the high
      mortality rate.

PMID- 14693476
TI  - [Characteristics of the patients seen in 1999 by referral centres for sexually
      transmitted diseases in Ceara (Northeast Brazil)].
AB  - Since 1995, in the State of Ceara, in Northeast Brazil, there is a public health
      project focusing on training and continuing education of health reference teams
      taking care of patients with sexually transmitted diseases (STD). An information
      system including a patient's form was worked out and established. The
      characteristics of the patients seen at consultation in 1999 are described. Ten
      units provided 1,478 filled forms. Women are more present than men (72% vs 28%).
      Multipartnership during the last three months is more frequent among males (52%)
      than among females (5%). Taking antibiotics prior to the first medical advice was
      frequent in the male population (17%). The main syndromes presented by women were
      vaginal discharge (81%) and genital warts (19%), whereas with men genital warts
      (47%) and urethral discharge (43%) were more frequent. The frequency of positive
      serology for syphilis and HIV among patients presenting an STD syndrome was 7.9%
      and 1.3%, respectively. It was higher among males (12% and 3%) than among females
      (7% and 1%). The way the referral facilities are used is different according to
      sex, the women corning more often spontaneously. The need for accurate etiologic
      data for each STD syndrome was identified. The analysis of the data resulting
      from these STD referral units allowed to produce relevant information whose
      follow-up will be of great interest for both health professionals and decision
      makers.

PMID- 14693477
TI  - [Victims of violence in urban secondary schools in Sousse (Tunisia)].
AB  - Most often epidemiologic studies of violence during adolescence focus on aspects
      related to the perpetrator. The adolescent victims of violence are certainly at
      least as numerous, but too little is known about them. Our aim was to estimate
      the extent of this social phenomenon and to identify its various forms, through a
      descriptive, cross-sectional study of a sample of 685 teenagers (409 girls and
      276 boys) from six public high schools in Sousse in 1999. A school physician
      conducted structured interviews to collect the data, recorded in compliance with
      the ethical rules of confidentiality and anonymity. The results indicate that
      36.9% of the adolescents (54% of the boys and 24% of the girls) reported
      experiencing violence. Within the group of victims, physical violence was
      reported by 78% of the boys and 63% of the girls, verbal violence by 51% and 63%,
      respectively. We conclude that experiencing violence is far from uncommon and
      that it causes acute suffering for youngsters during an important phase of their
      emotional development and exposes them to the risk of becoming violent as adults.
      School medical staff can play a crucial role in the prevention and the management
      of this mistreatment.

PMID- 14693478
TI  - [Biomedical waste management in the Regional Hospital Center of Ziguinchor].
AB  - To make the hospital environment healthier for those it serves, the management of
      biomedical waste (BMW) was studied in the Ziguinchor Regional Hospital Center
      (RHC) in Senegal from 1 March through 15 March, 2000. The RHC incinerator had
      stopped operating in 1993. Problems in BMW management were observed at all
      levels. Neither identification nor sorting took place during collection. Waste
      bins were exposed everywhere. Workers, rather than carrying waste bins on their
      back or head, used rolling tables. BMW ended up in a shallow open pit where they
      were periodically burned. Workers collected, stored, and transported BMW without
      any type of protection (gloves, boots, masks, aprons, etc.). The principal
      determinants of this poor management appear to be inadequate funding and training
      for the cleaning staff, the staff's failure to realize the dangers, and their use
      of non-standardized practices, due to the absence of BMW policies. BMW management
      at Ziguinchor RHC must be corrected. Protective equipment must be used
      systematically. Similarly, standardized practices must be applied to the
      decontamination of used objects, the identification and sorting at the source,
      the recovery and recycling of all objects with any remaining value, and the
      correct storage of BMW. This waste must be transported under high security from
      its place of storage to its final disposal site. Deep burial has been selected as
      the most feasible method of disposal under current conditions. A year-long
      program has been proposed towards this end. Strategies include training,
      information, motivation, equipment, supervision and evaluation. The budget to
      implement this program is CFA 5,423,454 francs, distributed between training
      (22%), equipment (40%), construction of the pit, and follow-up (38%). The tasks
      are distributed between a public health doctor, department supervisors, and
      cleaning staff. The follow-up will include three quarterly inspections, at 3, 6,
      and 9 months and an evaluation at the end of the program. The effect of the
      program will be judged by the disappearance of unlawful dumping due to the
      disposal of all BMW in the RHS's deep burial pit.

PMID- 14693480
TI  - [Intracranial tuberculoma in Africa, with no available neuroimaging. Case report
      and review of the literature].
AB  - The numerous extrapulmonary manifestations of tuberculosis have been well
      described. Intracranial localizations, including brain stem tuberculoma, are very
      rare. The authors report a case of brain tuberculoma in a patient with a history
      of primary pulmonary tuberculosis successfully treated more than twenty years
      earlier. The patient presented with signs of infection, although the fever
      disappeared temporarily after successive treatments for malaria (confirmed
      Plasmodium faiciparum), as well as neurological signs with left hemiparesis.
      Chest radiographs showed no signs of progressive pulmonary tuberculosis, and
      blood tests, cerebrospinal fluid testing, and HIV serology were all negative.
      Treatments for maxillary sinusitis, the malaria, bacterial meningitis, and
      cerebral abscess were equally ineffective. Brain stem tuberculoma was diagnosed
      only when the patient was transferred to a hospital equipped with neuroimaging
      equipment and was confirmed after histopathological examination of the
      intracranial lesion biopsies and the detection of mycobacterium DNA by polymerase
      chain reaction (PCR) in the cerebrospinal fluid. A review of 147 cases of
      intracranial tuberculoma reported in Africa between 1985 and 2001 points out the
      difficulties of both the differential diagnosis (tuberculoma or other
      intracranial space-occupying lesions) and treatment in African areas where
      neuroimaging is unavailable. Our patient's brainstem tuberculoma probably
      resulted from reactivation of latent tuberculosis.

PMID- 14693479
TI  - [Metal contamination of the ground water in Mohammedia (Morocco)].
AB  - This aim of this study was to assess the heavy metal contamination of the ground
      water in the Moroccan city of Mohammedia and its relation to the highly developed
      industrial and domestic activities in the region. Six heavy metals, Cu, Zn, Cd,
      Hg, Fe and Pb, were assayed in the waters of 19 wells throughout the city, in
      industrial areas, public landfills, and residential zones. Four sampling
      campaigns were conducted between January and May 1999. Analysis of the heavy
      metal levels revealed a causal relation between the human activities at the sites
      studied and the degree of contamination recorded. The sites in the industrial
      areas had elevated concentrations of Fe, Zn, Cu or Pb and most often a
      combination of at least two of these at a single site. Moreover, the spatial
      distribution of this pollution showed water in S7 areas to be high in iron and
      that in S5 and S7 (industrial) areas high in mercury. The concentrations measured
      are respectively 2.5 and 3-5 times greater than the Maximum Acceptable
      Concentration (MAC) recommended by WHO for potable water. This work has
      conclusively proven the presence of dangerous heavy metal contamination of the
      ground water supply in the area of Mohammedia; it demonstrates the need for
      conservation and antipollution measures aimed against heavy metal contamination
      of the overall water supply and in particular the ground water.

PMID- 14693481
TI  - [Minilaparotomy with a mini-pfannenstiel incision for the early diagnosis of
      ectopic pregnancy in Africa].
AB  - OBJECTIVE: to evaluate the usefulness of an exploratory minilaparotomy under
      local anaesthesia in cases of suspected ectopic pregnancy. PATIENTS AND METHODS:
      Prospective study of the management of all cases of unruptured suspected ectopic
      pregnancy at the Gynaecological and Obstetrical Clinic at the Dakar University
      teaching hospital from 1 January, 2000, to 31 December, 2002. RESULTS: 44
      unruptured ectopic pregnancies were recorded. The typical patient had no or few
      previous deliveries and was 30 years old; 27% of the patients presented risk
      factors for ectopic pregnancy. The principal motive for consultation was abnormal
      menstruation and pelvic pain; however, these symptoms together with a lateral
      uterine mass appeared in only 29.5% of the cases. Ultrasound examination was
      performed systematically and beta-HCG assessed for 36.8% of patients. The
      diagnostic was considered certain in 13.6% of the cases, probable in 36.3% and
      possible in 50%. Laparotomy was performed when the diagnosis was sure or
      probable, and an exploratory minilaparotomy was undertaken when the ectopic
      diagnosis was possible but uncertain. The diagnosis was confirmed in 79. 5% of
      the cases. The laparotomy failure rate was 18.7%, compared with 27.2% for the
      exploratory minilaparotomy, but the difference observed was not statistically
      significant (p=0.80). CONCLUSION: In view of the equipment problems that make
      beta-HCG assays and laparoscopy difficult to perform in Africa, the
      minilaparotomy under local anaesthesia is a useful alternative.

PMID- 14693482
TI  - Role of mast cells in dermatofibroma: recent viewpoints into the pathogenesis.
AB  - Mast cells are often discussed to play an important role in the tissue fibrotic
      process, because increased numbers of mast cells are found in the fibrous
      lesions. Recent evidence has revealed that mast cells are a rich source of
      cytokines or mediators, which are supposed to play a crucial role in altering the
      environmental extracellular matrix, leading to fibrosis. Dermatofibromas (DFs)
      are benign tumors histologically characterized by local fibroblast proliferation.
      It has been demonstrated that multiple DFs occur in patients with autoimmune
      diseases or under immunosuppressive therapy, implying that DFs are reactive
      tumors, rather than true neoplasms, at least in one aspect. Increased numbers of
      mast cells are also found in both solitary and multiple DFs, in particular in the
      layers between the DF lesion and the overlying epidermis. The presence of mast
      cells could be significant in the induction of several histopathologic changes,
      including acanthosis of the overlying epidermis, basal melanosis, and possibly
      mononuclear cell recruitment, in DF. Further elucidation of the role of mast
      cells may lend support to the understanding of the mechanism of DF.

PMID- 14693483
TI  - Human immunodeficiency virus type 1 (HIV-1) derived vectors: safety
      considerations and controversy over therapeutic applications.
AB  - The latest generation of lentiviral vectors based on HIV-1 is one of the most
      efficient tools for gene transduction of mammalian cells. However, the possible
      employment of HIV-based vectors in clinical trials is a very controversial issue,
      mainly due to safety and ethical concerns. HIV-1 is a lethal pathogenic agent,
      which induces AIDS. Genetic vectors must derive either from viruses that are not
      pathogenic in humans, or that eventually just cause mild illnesses. Patients
      exposed to HIV-based vectors will test seropositive to certain components of HIV
      1. In addition, there might be other possible adverse effects in patients that
      cannot be predicted, as many aspects of the pathogenesis of AIDS have not been
      completely understood yet. On these grounds, it seems necessary to improve the
      design of other lentiviral vectors, which derive from viruses that are not
      pathogenic in humans and are distantly related to primate retroviridae.

PMID- 14693484
TI  - Large congenital melanocytic nevi may reflect paradominant inheritance implying
      allelic loss.
AB  - Large congenital melanocytic nevi have so far always been considered to occur
      sporadically, and until now little has been written about a possible role of
      heredity as a cause of this disorder. We reviewed familial cases of large
      congenital melanocytic nevi as reported in the literature and found 14 case
      reports with a family history of congenital nevi. We propose the concept of
      paradominant inheritance as a possible genetic explanation. The concept would
      imply that heterozygous individuals are phenotypically normal which is why the
      mutation would be transmitted unperceived through many generations. The trait
      would become manifest only when loss of heterozygosity occurred at an early
      developmental stage, giving rise to a patchy area of homozygous or hemizygous
      cells. This would explain why the lesions of large congenital melanocytic nevi
      are always arranged in a mosaic pattern; why they occur virtually always
      sporadically; and why the exceptional cases of a familial aggregation of this
      trait do not show any consistent Mendelian pattern.

PMID- 14693485
TI  - Effect of topical tretinoin, chemical peeling and dermabrasion on p53 expression
      in facial skin.
AB  - The tumour suppressor protein p53 is a phosphoprotein that is activated by DNA
      damage. It is involved in the decision whether the cells should stop replication
      and proceed to repair their DNA, or to die by apoptosis. In the present study, we
      evaluate the effect of some treatment modalities on the expression of p53 in
      facial skin. Biopsy specimens were obtained from the facial skin of 20 patients
      before and after treatment using topical tretinoin (11 cases), TCA chemical
      peeling (5 cases) and dermabrasion (4 cases). Biopsy specimens were also obtained
      from 12 control subjects representing the same age groups of the patients.
      Topical tretinoin therapy was found to induce a significant decrease in the
      expression of p53 up to 6 months of therapy followed by a significant increase
      after 10 months of therapy. On the contrary, superficial TCA peeling did not
      induce any statistically significant change in the expression of p53. On the
      other hand dermabrasion was found to induce a significant decrease in the level
      of expression of p53 in biopsies obtained after complete re-epithelialization
      followed by a significant increase. These changes in the expression of p53 may
      play a role in mediating the effects of such treatment modalities on the
      epidermis, as well as prevention of actinic neoplasia by adjusting any
      disturbance in the proliferation/apoptosis balance observed in photoaged facial
      skin.

PMID- 14693486
TI  - Immunohistochemical study of carbonic anhydrase isozymes in human skin.
AB  - An increasing number of carbonic anhydrase (CA) isozymes have been discovered in
      human organs. However, there is little evidence concerning their expression in
      mammal skin, humans included, and the isozymes involved have not been identified
      yet. In this study, the distribution of three CA isozymes I, II and IX in human
      skin from healthy subjects was investigated using an immunohistochemical
      technique. Specific staining for CA I and II was detected in the basolateral
      plasma membrane of the epithelial cells of the spinous and basal layers of
      epidermis as well as in the endothelium of capillaries in the papillary dermis. A
      marked CA II immunoreactivity was mostly found in secretory cells of the sweat
      glands. No signal for CA IX was detected but on the plasma membranes and the
      cytoplasm of cells surrounding the hair shaft. The significance and biological
      role of CA isozymes expression in human skin is discussed.

PMID- 14693487
TI  - Cimetidine treatment for viral warts enhances IL-2 and IFN-gamma expression but
      not IL-18 expression in lesional skin.
AB  - Cimetidine has been shown to improve various types of human neoplasms and more
      recently it has been shown to be effective in treating recalcitrant or multiple
      viral warts in some reports. However, it is not well understood why cimetidine is
      effective on those kinds of viral warts. We investigated 55 patients with
      multiple viral warts treated only with oral cimetidine for up to 4 months to
      examine the efficacy of treatment. The patients were divided into two groups:
      group A received oral cimetidine (<20 mg/kg/day) and group B received the drug
      (30 to 40 mg/kg/day). In addition, using real time PCR, we measured mRNA levels
      of the cytokines interleukin-2 (IL-2), IL-18, and interferon (IFN)-gamma taken
      from selected punch biopsy specimens before and during treatment. As a result,
      34.5% (19/55) of the patients had a dramatic clinical improvement or complete
      remission (CR) of their viral warts and 23.6% (13/55) of the patients had partial
      responses (PR) within 4 months of cimetidine therapy. IL-2 and IFN-gamma mRNA
      levels were significantly increased and IL-18 mRNA levels were decreased in
      tissues of effectively treated viral warts. Our results show that the higher dose
      of oral cimetidine was more effective in treating multiple viral warts, that
      cimetidine activates Th1 cells to produce IL-2 and IFN-c and that their
      expression correlates with wart remission. These results suggest that cimetidine
      is an effective treatment for viral warts. In addition, based on the decrease in
      IL-18 mRNA elicited by the drug, IL-18 might be expressed by keratinocytes
      infected with HPV.

PMID- 14693488
TI  - Comparison of 99mTc-MIBI scintigraphy and sentinel node biopsy in the detection
      of occult lymph node metastases from cutaneous melanoma.
AB  - 99mTc-MIBI scintigraphy has been proposed as a technique that can diagnose
      clinically undetectable melanoma metastases. The aim of the study was to compare
      the sensitivity of 99mTc-MIBI with that of sentinel node biopsy (SNB) in the
      detection of nodal disease. Twenty-eight patients with melanoma >1.0 mm thick
      were enrolled. Patients underwent 99mTc-MIBI scintigraphy and a preoperative
      lymphoscintigraphy followed by SNB. Sentinel nodes were identified in 27/28
      patients. Twelve patients had an involved sentinel node (SN), being 99mTc-MIBI
      positive in 10. No patient with negative SNB developed regional recurrence during
      the study. 99mTc-MIBI had a sensitivity of 83% and a specificity of 93%. We
      conclude that SNB remains the procedure of choice for detecting subclinical lymph
      node involvement from melanoma. 99mTc-MIBI could have an alternative role in
      lymph node staging of patients who are not good candidates of SNB, that needs to
      be tested in appropriate trials.

PMID- 14693489
TI  - Non-steroidal topical immunomodulators provide skin-selective, self-limiting
      treatment in atopic dermatitis.
AB  - Topical corticosteroids are the mainstay of treatment for atopic dermatitis;
      however, their clinical utility is limited by potential side effects. Recently,
      the steroid-free topical immunomodulators tacrolimus ointment and pimecrolimus
      cream have become available. These agents provide effective treatment without
      causing skin atrophy or other steroidal side effects, and their physiochemical
      properties, such as relatively large molecular size and high lipophilicity, limit
      diffusion through skin and into the bloodstream, providing skin-selective
      treatment. Clinical trials with more than 1,700 paediatric and adult patients
      have demonstrated that treatment with either agent is associated with minimal
      systemic absorption of tacrolimus or pimecrolimus. Additionally, studies have
      shown that percutaneous absorption of tacrolimus decreases as treatment continues
      and clinical improvement occurs. This self-limiting facet of the treatment,
      together with the skin-selectivity of topical immunomodulators, is reflected in
      the good safety and tolerability profiles of these agents, which promise to
      significantly improve the long-term management of atopic dermatitis.

PMID- 14693490
TI  - Radiotherapy of carcinomas of the skin overlying the cartilage of the nose:
      results in 405 lesions.
AB  - The skin overlying the nose cartilage is a particularly frequent localization of
      skin carcinomas, for which it is of great practical interest to identify the best
      therapy, able to combine effectiveness with a good cosmetic and functional
      result. To this aim a retrospective study was performed regarding 405 basal and
      squamous cell carcinomas treated by kilovoltage radiotherapy in the period 1972
      2002. The total dose of ionizing radiation administered ranged from 40 to 85 Gy,
      with different dose fractionations, according to the technique employed. The five
      year cure-rate was 88.6%. Cosmetic results were evaluated as "good" or
      "acceptable" in 96.13% of the treated lesions in complete remission. So far, no
      complications nor sequelae to the radiological treatment have been observed. Our
      results show that superficial radiotherapy is able to provide high rates of
      remission in the treatment of nose basal and squamous cell carcinomas, without
      damaging the underlying cartilaginous tissues.

PMID- 14693491
TI  - Long-term efficacy and safety of topical tacrolimus in the management of
      ulcerative/erosive oral lichen planus.
AB  - The long-term safety and clinical benefit of topical tacrolimus for the
      management of erosive or ulcerative oral lichen planus has not been evaluated. 50
      adults (39 female 11 male; group median age 59, range 29-88 years) with
      symptomatic, erosive or ulcerative lichen planus recalcitrant to topical
      corticosteroids applied 0.1% topical tacrolimus ointment twice daily to
      symptomatic mucosal lesions. Topical tacrolimus was applied for a median time of
      19.8 months (range 2-39 months) in this patient group. Fourteen percent of the
      patients had complete resolution of ulcers or erosions, 80% partial resolution
      and 6% reported no clinical benefit. The most common adverse effects were a
      burning sensation (16%) at the site of application and transient taste
      disturbance (8%). No significant, long-standing changes in hepatic or renal
      biochemistry were observed. The mean tacrolimus level decreased with duration of
      therapy from 2.7 microg/l (week 1) to 0.5 microg/l (week 32). 0.1% topical
      tacrolimus is an effective means of controlling the symptoms and signs of erosive
      or ulcerative oral lichen planus and has no notable adverse effects over a mean
      duration of application of 19.8 months.

PMID- 14693492
TI  - Topical tacrolimus: an effective therapy for facial psoriasis.
AB  - We evaluated twenty-one cases of facial psoriasis lesions treated with topical
      tacrolimus ointment. Patients were 15 males and 6 females with a mean age of 51.1
      years old. Mean duration of the disease was 10.1 years. 0.1% tacrolimus ointment
      was applied twice a day for 4 weeks without occlusion. A complete or good
      response was obtained in 10 (47.6%) and 9 (42.9%) patients, respectively. The
      mean score of erythema decreased from 1.76 to 0.62, that of infiltration
      decreased from 1.33 to 0.43, and that of desquamation decreased from 0.95 to
      0.24, respectively. These data demonstrate that topical tacrolimus is effective
      for facial lesions of psoriasis without occlusion. We conclude that topical
      tacrolimus is an effective treatment for facial psoriasis.

PMID- 14693493
TI  - A case study to evaluate the treatment of vitiligo with khellin encapsulated in L
      phenylalanin stabilized phosphatidylcholine liposomes in combination with
      ultraviolet light therapy.
AB  - Vitiligo destroys the melanocytes in the epidermis; the inactive melanocytes in
      the outer root sheaths are not affected. Phosphatidylcholine liposomes are able
      to target molecules contained in them into the hair follicles. Khellin is
      activated by UVA and previous studies have shown that a combination of khellin
      and UVA (KUVA) can be effective in the treatment of vitiligo. The aim of this
      study was to determine in an open trial the efficacy and safety of treatment with
      khellin encapsulated in L-phenylalanine stabilized phosphatidylcholine liposomes
      in combination with UVA/UVB light therapy(KPLUV) in 74 subjects with vitiligo.
      After a mean treatment period of 12 months (range 10-14 months) 72% of the
      treated locations had a repigmentation response of 50% to 100%. Repigmentation of
      75-100% was achieved on the face in 63%, the back in 59%, the arms in 58%, the
      trunk in 57%, the legs in 56% and on the hands in 4% of the patients. Side
      effects were not seen with KPLUV. The patients in the control group, only treated
      with UVA/B-light, hardly showed any repigmentation. This indicates that the
      exposure of the skin to UV light alone is not responsible for the results of
      KPLUV.

PMID- 14693494
TI  - Drug Hypersensitivity Syndrome in a West-Indian population.
AB  - Some studies have suggested an ethnic susceptibility to Hypersensitivity
      Syndrome. We did a 7-year-prospective study in Guadeloupe whose population is
      mainly of African ancestry, and has free access to modern care facilities. Most
      patients included were Afro-Caribbeans (26/28), and females (20/28). However,
      ethnic distribution did not reach significant conclusions. Annual incidence rate
      was estimated at 0.9/100,000. Medium incubation and duration were 33 and 66 days
      respectively. Two patients with grade 4 hepatitis died from the syndrome. Two
      thirds of the patients were given prednisone, which usually alleviated the
      systemic symptoms, but did not prevent their development (in 5 patients) nor
      death. Carbamazepine, allopurinol, and minocycline accounted for 2/3 of the
      cases. Sixty four percent of the causative prescriptions were judged
      inappropriate. DHS appeared as the most frequent type of severe systemic drug
      reaction in this population, and may largely be prevented by rational
      prescribing.

PMID- 14693495
TI  - Results of surveillance programme aimed at early diagnosis of cutaneous melanoma
      in high risk Mediterranean subjects.
AB  - OBJECTIVE: To investigate the impact of a surveillance program aimed at early
      diagnosis of melanoma in a cohort of subjects classified at risk on the basis of
      their number of nevi. To compare the number of observed cases of melanoma in the
      cohort to that expected number in the general population of the same area.
      METHODS: Two hundred and eighteen subjects with no personal or family history of
      melanoma residing in the Florence district who showed more than 30 common
      acquired nevi and 3 or more atypical nevi (high-risk) have been followed for an
      average period of 3.4 years (range 1-6.5); an additional intermediate-risk group
      with 237 subjects was also enrolled. RESULTS: Four incident melanomas were
      detected in 218 high-risk subjects followed for a total of 741.7 person-years; no
      melanoma was detected in the lower risk group. All the 4 detected melanomas were
      in situ (Clark level I), with an average interval since enrollment of 4.6 years
      (range 1.4-6.5). In accordance with age-and sex-specific incidence rates of
      melanoma (including in situ forms) in the general population of the area, the
      standardized incidence ratio (SIR) in the cohort was 44.1 (95% CI 16.5-117.5).
      CONCLUSIONS: Subjects with more than 30 common nevi and 3 or more atypical nevi
      show about a 40-fold increased risk of developing melanoma. Even allowing for
      some degree of diagnostic anticipation due to periodic controls the risk appears
      higher than in the intermediate risk population. As a consequence of active
      follow up of individuals, all the detected tumors were at favourable prognosis.
      Periodic examination of these subjects should therefore be recommended as part of
      a prevention program for cutaneous melanoma in southern European populations.

PMID- 14693496
TI  - Apocrine carcinoma developed in nevus sebaceus of Jadassohn.
AB  - Apocrine skin carcinoma (ASC) is a rare aggressive cutaneous tumor. We describe a
      case of ASC occurring on a nevus sebaceus of Jadassohn (NSJ) in a 66-year-old
      man. Malignant degeneration of NSJ is a rare complication usually found in
      elderly patients. Most of these tumors are basal cell carcinomas or squamous cell
      carcinomas. Only five cases of ASC on NSJ have been previously reported. This
      report recalls the potential of NSJ for degeneration.

PMID- 14693497
TI  - Acrokeratoelastoidosis associated with nodular scleroderma.
AB  - We report a case of acrokeratoelastoidosis associated with nodular scleroderma, a
      variant of localized scleroderma. The patient showed no clinical and laboratory
      signs of systemic scleroderma. Because there is a paper describing the
      association of acrokeratoelastoidosis with systemic scleroderma, coexistence of
      acrokeratoelastoidosis and nodular scleroderma in the patient suggests that
      acrokeratoelastoidosis is related to localized nodular scleroderma as well as
      systemic scleroderma.

PMID- 14693498
TI  - Febrile ulceronecrotic Mucha-Habermann disease with extensive skin necrosis in
      intertriginous areas.
AB  - Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a severe variant of
      pityriasis lichenoides et varioliformis acuta characterized by high fever and
      papulonecrotic skin lesions. Here we report a case of a 14-year-old boy with
      typical features of FUMHD and unusual manifestation of extensive skin necrosis in
      intertriginous regions including axillae, neck, inguinal and antecubital areas.
      Systemic administration of corticosteroid and erythromycin led to rapid healing
      of ulcerations without residual scar formation. Review of the literature showed
      male-predominance and favorable outcome in pediatric cases of FUMHD.

PMID- 14693499
TI  - Phalangeal microgeodic syndrome and pine processionary caterpillar.
AB  - We describe an 11-month-old-girl with a 1-month history of edematous fingers. She
      had been hospitalized 3 months before for a mucocutaneous reaction to a
      processionary caterpillar. Manifestations of arthritis or systemic illness were
      absent. Radiographs of fingers showed small round lytic lesions within the middle
      and distal phalanges. A diagnosis of 'Phalangeal Microgeodic Syndrome' (PMS) was
      established. Bone biopsy of an osteolytic lesion showed fibrosis and foreign
      bodies with hair aspect surrounded by an epithelioid granuloma. PMS signs include
      sub-acute swelling and redness of fingers associated with microgeodic osteolytic
      lesions of phalanges. Sickle-cell anemia, syphilis, osteomyelitis, tuberculosis
      and sarcoidosis are the main differential diagnoses to exclude. The etiology is
      still unknown. Circulatory disturbances in the phalanges exposed to low
      temperatures have been mentioned by several authors. We describe the first case
      of PMS in a child with a clear history of play with a caterpillar and the
      presence of a caterpillar hair with epithelioid granuloma in an osteolytic
      lesion.

PMID- 14693500
TI  - Disseminated lupus vulgaris.
AB  - Lupus vulgaris is the most common form of cutaneous tuberculosis, and usually
      presents as a solitary lesion on the face. We report two patients with multiple
      lesions on different skin areas. The first patient presented a diffuse
      involvement of the right foot, and reddish-brown plaques on the right leg, the
      back and the face. Spreading of the lesions followed a prolonged application of
      topical corticosteroids. The second patient showed a large plaque on the nape and
      occipital area resulting in scarring alopecia, and plaques on the right inguinal
      and thigh regions. Ziehl-Neelsen staining was negative in both cases, but
      diagnosis was supported by histology and polymerase chain reaction analysis. No
      visceral involvement was present. Antituberculosis polychemotherapy was rapidly
      effective.

PMID- 14693501
TI  - Solid facial edema of acne: failure of treatment with isotretinoin.
AB  - Solid facial edema of acne is a rare persistent skin condition which occurs as a
      late complication of acne vulgaris. It is difficult to treat and isotretinoin
      seems to be the most effective agent. Here we present a 25-year-old man with a
      facial edema which arose after the complete remission of acne. Treatment with
      isotretinoin for 4 months was unsuccessful in this case.

PMID- 14693502
TI  - Basaloid follicular hamartoma with eruptive milia and hypohidrosis: is there a
      pathogenic relationship ?
AB  - We report a sporadic case of eruptive milia with histopathological features of
      basaloid follicular hamartoma which developed in an 8 year-old Japanese girl.
      Multiple milia and comedo-like eruptions were present at birth and gradually
      increased in number and spread over the extremities. Histopathologically,
      keratotic cysts with trichilemmal keratinization and features of basaloid
      follicular hamartoma were observed without any histological findings of basal
      cell epithelioma or trichoepithelioma. Reduced sweating was observed after
      iontophoretically applied acetylcholine on the forearm. Nevus of Ota and thyroid
      goiter were complications.

PMID- 14693503
TI  - Amyloid deposition associated with generalized morphea-like scleroderma.
AB  - A 62-year-old man with amyloid deposition associated with generalized morphea
      like scleroderma is described. He had been occupationally exposed to organic
      solvents. Physical examination showed sclerosis of fingers, forearms, and trunk.
      Erythema was noted on the border of patchy sclerotic plaques on his chest and
      back. In addition, firm miliary, keratotic papules were found on the lateral
      forearms. Amyloid deposition was demonstrated by Congo-red stain at papillary
      layers of overlying sclerotic dermis in the biopsied specimen taken from the left
      forearm. As far as we know, amyloid deposition associated with generalized
      morphea-like scleroderma has not been reported until now.

PMID- 14693504
TI  - Involvement of mast cells in basal and neurotensin-induced intestinal absorption
      of taurocholate in rats.
AB  - Neurotensin (NT), a hormone released from intestine by ingested fat, facilitates
      lipid digestion by stimulating pancreatic secretion and slowing the movement of
      chyme. In addition, NT can contract the gall bladder and enhance the
      enterohepatic circulation (EHC) of bile acids to promote micelle formation. Our
      recent finding that NT enhanced and an NT antagonist inhibited [(3)H]taurocholate
      ([(3)H]TC) absorption from proximal rat small intestine indicated a role for
      endogenous NT in the regulation of EHC. Here, we postulate the involvement of
      intestinal mast cells in the TC uptake process and in the stimulatory effect of
      NT. In anesthetized rats with the bile duct cannulated for bile collection,
      infusion of NT (10 pmol.kg(-1).min(-1)) enhanced the [(3)H]TC recovery rate from
      duodenojejunum by 2.2-fold. This response was abolished by pretreatment with mast
      cell stabilizers (cromoglycate, doxantrazole) and inhibitors of mast cell
      mediators (diphenhydramine, metergoline, zileuton). In contrast, mast cell
      degranulators (compound 48/80, substance P) and mast cell mediators (histamine,
      leukotriene C(4)) reproduced the effect of NT. N(G)-nitro-l-arginine methyl ester
      enhanced and l-arginine inhibited basal and NT-induced TC uptake, consistent with
      the known inhibitory effect of nitric oxide (NO) on mast cell reactivity. These
      results argue that basal and NT-stimulated TC uptake in rat jejunum are similarly
      dependent on mast cells, are largely mediated by release of mast cell mediators,
      and are subject to regulation by NO.

PMID- 14693505
TI  - Inhibition of acid secretion by the nonsteroidal anti-inflammatory drugs
      diclofenac and piroxicam in isolated gastric glands: analysis of a multifocal
      mechanism.
AB  - In nonstimulated rabbit gastric glands, acetylsalicylic acid (10-500 microM) and
      indomethacin (3-300 microM) did not significantly modify the basal rate of acid
      secretion, whereas diclofenac and piroxicam (10-1,000 microM each) caused a
      marked and dose-dependent inhibitory effect (EC(50) = 138 and 280 microM,
      respectively). In gastric glands stimulated by histamine (100 microM), diclofenac
      also reduced the rate of acid formation in a dose-dependent manner. In contrast,
      acetylsalicylic acid, indomethacin, and piroxicam exerted a biphasic effect; thus
      low concentrations (3-100 microM) of these three agents significantly increased
      the rate of histamine-stimulated acid secretion (10-20% over the corresponding
      control value) by a cAMP-independent mechanism, whereas higher concentrations
      reduced the rate of acid formation. With respect to underlying biochemical
      mechanisms that could mediate inhibitory effects of NSAIDs on gastric acid
      formation, it was observed that both diclofenac and piroxicam, but not
      acetylsalicylic acid or indomethacin, decreased the glandular content of ATP,
      inhibited hydrolytic activity of gastric gland microsomal H(+)-K(+)-ATPase, and
      reduced the rate of H(+)-K(+)-ATPase-dependent proton transport across microsomal
      membranes in a dose-dependent manner. Furthermore, diclofenac and piroxicam also
      significantly increased passive permeability of microsomal membranes to protons.
      In conclusion, our work shows that diclofenac and piroxicam cause a significant
      reduction in the rate of basal and histamine-stimulated acid formation in
      isolated rabbit gastric glands at concentrations that can be attained in the
      gastric lumen of patients treated with these drugs. Mechanisms involved in these
      inhibitory effects appear to be multifocal and include different steps of
      stimulus-secretion coupling.

PMID- 14693506
TI  - Soluble complement receptor 1 preserves endothelial barrier function and
      microcirculation in postischemic pancreatitis in the rat.
AB  - Components of the activated complement cascade are considered to play a pivotal
      role in ischemia-reperfusion-induced organ injury. With the use of intravital
      epifluorescence microscopy, we investigated the effect of complement inhibition
      by the recombinant soluble complement receptor 1 (sCR1; TP10) on the effect of
      macromolecular microvascular permeability, functional capillary perfusion, and
      leukocyte endothelium interaction in postischemic pancreatitis. Anaesthetized
      Sprague-Dawley rats were subjected to 60 min of normothermic pancreatic ischemia
      induced by microclipping of the blood-supplying arteries of the organ. Rats who
      received sCR1 (15 mg/kg body wt iv; n = 7) during reperfusion showed a
      significant reduction of permeability (1.77 +/- 1.34 x 10(-8) cm/s; n = 7) of
      tetramethylrhodamine isothiocyanate-labeled albumin injected 90 min after the
      onset of reperfusion compared with vehicle-treated animals (6.95 +/- 1.56 x 10(
      8) cm/s; n = 7). At 120 min after the onset of reperfusion, the length of red
      blood cell-perfused capillaries (functional capillary density) was significantly
      improved (from 279 +/- 15.7 to 330 +/- 3.7 cm(-1); n = 7) and the number of
      leukocytes adherent to postcapillary venules was significantly reduced (from 314
      +/- 87 to 163 +/- 71 mm(-2); n = 7) by sCR1 compared with vehicle treatment.
      Complement inhibition by sCR1 effectively ameliorates pancreatic ischemia
      reperfusion-induced microcirculatory disturbances and might be considered for
      treatment of postischemic pancreatitis.

PMID- 14693507
TI  - Active involvement of PKC for insulin-mediated rates of muscle protein synthesis
      in Zucker rats.
AB  - A recent report from our group demonstrated that insulin facilitates muscle
      protein synthesis in obese Zucker rats. The purpose of this study was to
      determine whether PKC, a probable modulator of insulin signal transduction and/or
      mRNA translation, has a role in this insulin-mediated anabolic response. In the
      first portion of the study, gastrocnemius muscles of lean and obese Zucker rats
      (n = 5-7 for each phenotype) were bilaterally perfused with or without insulin to
      assess cytosolic and membrane PKC activity. Limbs perfused with insulin
      demonstrated greater PKC activity in both lean and obese Zucker rats (P < 0.05)
      compared with no insulin, but overall activity was greater in obese animals (by
      approximately 27% compared with lean, P < 0.05). To determine whether PKC plays a
      role in muscle protein synthesis, hindlimbs (n = 6-8 for each phenotype) were
      bilaterally perfused with or without insulin and/or GF-109203X (GF; a PKC
      inhibitor). The presence of GF did not influence the rates of insulin-mediated
      protein synthesis in gastrocnemius muscle of lean Zucker rats. However, when
      obese rats were perfused with GF (P < 0.05), the effect of insulin on elevating
      rates of protein synthesis was not observed. We also used phorbol 12-myristate 13
      acetate (TPA, a PKC activator; n = 5-7 for each phenotype) with and without
      insulin to determine the effect of PKC activation on muscle protein synthesis.
      TPA alone did not elevate muscle protein synthesis in lean or obese rats.
      However, TPA plus insulin resulted in elevated rates of protein synthesis in both
      phenotypes that were similar to rates of insulin alone of obese rats. These
      results suggest that PKC is a modulator and is necessary, but not sufficient, for
      insulin-mediated protein anabolic responses in skeletal muscle.

PMID- 14693508
TI  - Rapid downregulation of adipose tissue lipoprotein lipase activity on food
      deprivation: evidence that TNF-alpha is involved.
AB  - When food was removed from young rats in the early morning, adipose tissue tumor
      necrosis factor (TNF)-alpha activity increased 50% and lipoprotein lipase (LPL)
      activity decreased 70% in 6 h. There was a strong negative correlation between
      the TNF-alpha and LPL activities. Exogenous TNF-alpha further decreased LPL
      activity. Pentoxifylline, known to decrease production of TNF-alpha, had no
      effect on LPL activity in fed rats but almost abolished the rise of TNF-alpha and
      the decrease of LPL activity in rats deprived of food. The specific activity of
      LPL decreased from 0.92 mU/ng in fed rats to 0.35 and 0.24 mU/ng in rats deprived
      of food given saline or TNF-alpha, indicating a shift in the LPL molecules toward
      an inactive state. Lipopolysaccharide increased adipose tissue TNF-alpha and
      decreased LPL activity. Both of these effects were strongly impeded by
      pretreatment of the rats with pentoxifylline, or dexamethasone. Pretreatment of
      the rats with actinomycin D virtually abolished the response of LPL activity to
      food deprivation or exogenous TNF-alpha. We conclude that food deprivation, like
      lipopolysaccharide, signals via TNF-alpha to a gene whose product causes a rapid
      shift of newly synthesized LPL molecules toward an inactive form and thereby
      shuts down extraction of lipoprotein triglycerides by the adipose tissue.

PMID- 14693509
TI  - Quantifying rates of protein synthesis in humans by use of 2H2O: application to
      patients with end-stage renal disease.
AB  - A method is introduced for quantitating protein synthetic rates in humans by use
      of (2)H(2)O. Its validity was tested in subjects with end-stage renal disease.
      Six clinically stable subjects, hemodialyzed three times weekly, ingested
      (2)H(2)O to a body water (2)H enrichment of approximately 0.4%. On dialysis, body
      water enrichment declined to approximately 0.1%. Enrichment of the alpha-hydrogen
      of plasma free alanine was also approximately 0.4% before and approximately 0.1%
      after dialysis. Beta-hydrogen enrichment was approximately 80-100% of alpha
      hydrogen enrichment. (2)H(2)O was ingested to replace (2)H(2)O removed after each
      dialysis for 15-51 days, returning enrichment to approximately 0.4%. Enrichment
      of alanine from plasma albumin gradually increased, with again approximately 80
      100% as much (2)H in beta- as in alpha-hydrogens. With continued dialyses,
      without (2)H(2)O replacement, alanine from albumin enrichment gradually declined,
      whereas free alanine and water enrichments were negligible. The fractional
      albumin synthesis rate, calculated from the increase in enrichment in alanine
      from albumin, was 4.0 +/- 0.5%/day, and from the decrease, 4.6 +/- 0.2%/day. Thus
      body water enrichment in a subject given (2)H(2)O can be maintained constant long
      term. A rapid exchange, essentially complete, occurs between the hydrogens of
      alanine and body water. An integrated measure over a long period of albumin's
      synthetic rate can be estimated from both the rise in enrichment of alanine from
      the protein during (2)H(2)O ingestion and fall on (2)H(2)O withdrawal, while the
      subject's living routine is uninterrupted. Estimates are in subjects with renal
      disease, but the method should be applicable to estimates of protein synthetic
      rates in normal subjects and in other pathological states.

PMID- 14693511
TI  - Intensified exercise training does not alter AMPK signaling in human skeletal
      muscle.
AB  - The AMP-activated protein kinase (AMPK) cascade has been linked to many of the
      acute effects of exercise on skeletal muscle substrate metabolism, as well as to
      some of the chronic training-induced adaptations. We determined the effect of 3
      wk of intensified training (HIT; 7 sessions of 8 x 5 min at 85% Vo2 peak) in
      skeletal muscle from well-trained athletes on AMPK responsiveness to exercise.
      Rates of whole body substrate oxidation were determined during a 90-min steady
      state ride (SS) pre- and post-HIT. Muscle metabolites and AMPK signaling were
      determined from biopsies taken at rest and immediately after exercise during the
      first and seventh HIT sessions, performed at the same (absolute) pre-HIT work
      rate. HIT decreased rates of whole body carbohydrate oxidation (P < 0.05) and
      increased rates of fat oxidation (P < 0.05) during SS. Resting muscle glycogen
      and its utilization during intense exercise were unaffected by HIT. However, HIT
      induced a twofold decrease in muscle [lactate] (P < 0.05) and resulted in tighter
      metabolic regulation, i.e., attenuation of the decrease in the PCr/(PCr + Cr)
      ratio and of the increase in [AMPfree]/ATP. Resting activities of AMPKalpha1 and 
      alpha2 were similar post-HIT, with the magnitude of the rise in response to
      exercise similar pre- and post-HIT. AMPK phosphorylation at Thr172 on both the
      alpha1 and alpha2 subunits increased in response to exercise, with the magnitude
      of this rise being similar post-HIT. Acetyl-coenzyme A carboxylase-beta
      phosphorylation was similar at rest and, despite HIT-induced increases in whole
      body rates of fat oxidation, did not increase post-HIT. Our results indicate
      that, in well-trained individuals, short-term HIT improves metabolic control but
      does not blunt AMPK signaling in response to intense exercise.

PMID- 14693512
TI  - Growing group of extended-spectrum beta-lactamases: the CTX-M enzymes.

PMID- 14693513
TI  - Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella
      pneumoniae.
AB  - Klebsiella pneumoniae strain 11978 was isolated in Turkey in 2001 and was found
      to be resistant to all beta-lactams, including carbapenems. Cloning and
      expression in Escherichia coli identified five beta-lactamases, including two
      novel oxacillinases. The beta-lactamase OXA-48 hydrolyzed imipenem at a high
      level and was remotely related (less than 46% amino acid identity) to the other
      oxacillinases. It hydrolyzed penicillins and imipenem but not expanded-spectrum
      cephalosporins. The bla(OXA-48) gene was plasmid encoded and not associated with
      an integron, in contrast to most of the oxacillinase genes. An insertion
      sequence, IS1999, was found immediately upstream of bla(OXA-48). Another plasmid
      that encoded a second oxacillinase gene, bla(OXA-47), located inside a class 1
      integron was identified in K. pneumoniae 11978. OXA-47 had a narrow spectrum of
      hydrolysis activity and did not hydrolyze ceftazidime or imipenem, as is found
      for the beta-lactamase (OXA-1) to which it is related. In addition, beta
      lactamases TEM-1 and SHV-2a were expressed from the same K. pneumoniae isolate.
      Analysis of the outer membrane proteins of this isolate revealed that it lacked a
      porin of ca. 36 kDa. Thus, the high-level resistance to beta-lactams of this
      clinical isolate resulted from peculiar beta-lactamases and modification of outer
      membrane proteins.

PMID- 14693514
TI  - Escherichia coli mutators present an enhanced risk for emergence of antibiotic
      resistance during urinary tract infections.
AB  - Mutators may present an enhanced risk for the emergence of antibiotic resistance
      in bacteria during chemotherapy. Using Escherichia coli mutators as a model, we
      evaluated their ability to develop resistance to antibiotics routinely used for
      the treatment of urinary tract infections (UTIs). Under conditions that simulate
      therapeutic drug concentrations in humans, low-level resistance to trimethoprim,
      gentamicin, and cefotaxime emerged more frequently in mutators than normal
      strains. Resistance to trimethoprim in both cell types arose from a single point
      mutation in folA (Ile94-->Leu) and cefotaxime resistance resulted from loss of
      outer membrane porin OmpF. The mechanisms of gentamicin resistance could not be
      defined, but resistance did not result from mutations in ribosomal protein L6
      (rplF). Although similar mechanisms of low-level antibiotic resistance probably
      arise in these strains, mutators are a risk factor because the increased
      generation of mutants with low-level resistance enhances the opportunity for
      subsequent emergence of high-level resistance.

PMID- 14693515
TI  - High-throughput screen for inhibitors of transglycosylase and/or transpeptidase
      activities of Escherichia coli penicillin binding protein 1b.
AB  - Penicillin binding protein (PBP) 1b of Escherichia coli has both transglycosylase
      and transpeptidase activities, which are attractive targets for the discovery of
      new antibacterial agents. A high-throughput assay that detects inhibitors of the
      PBPs was described previously, but it cannot distinguish them from inhibitors of
      the MraY, MurG, and lipid pyrophosphorylase. We report on a method that
      distinguishes inhibitors of both activities of the PBPs from those of the other
      three enzymes. Radioactive peptidoglycan was synthesized by using E. coli
      membranes. Following termination of the reaction the products were analyzed in
      three ways. Wheat germ agglutinin (WGA)-coated scintillation proximity assay
      (SPA) beads were added to one set, and the same beads together with a detergent
      were added to a second set. Type A polyethylenimine-coated WGA-coated SPA beads
      were added to a third set. By comparison of the results of assays run in parallel
      under the first two conditions, inhibitors of the transpeptidase and
      transglycosylase could be distinguished from inhibitors of the other enzymes, as
      the inhibitors of the other enzymes showed similar inhibitory concentrations
      (IC(50)s) under both conditions but the inhibitors of the PBPs showed
      insignificant inhibition in the absence of detergent. Furthermore, comparison of
      the results of assays run under conditions two and three enabled the distinction
      of transpeptidase inhibitors. Penicillin and other beta-lactams showed
      insignificant inhibition with type A beads compared with that shown with WGA
      coated SPA beads plus detergent. However, inhibitors of the other four enzymes
      (tunicamycin, nisin, bacitracin, and moenomycin) showed similar IC(50)s under
      both conditions. We show that the main PBP being measured under these conditions
      is PBP 1b. This screen can be used to find novel transglycosylase or
      transpeptidase inhibitors.

PMID- 14693516
TI  - Effects of aspirin and other nonsteroidal anti-inflammatory drugs on biofilms and
      planktonic cells of Candida albicans.
AB  - Prostaglandins are now known to be produced by Candida albicans and may play an
      important role in fungal colonization. Their synthesis in mammalian cells is
      decreased by inhibitors of the cyclooxygenase isoenzymes required for
      prostaglandin formation. In the present study, a catheter disk model system was
      used to investigate the effects of nonsteroidal anti-inflammatory drugs (all
      cyclooxygenase inhibitors) on biofilm formation by three strains of C. albicans.
      Seven of nine drugs tested at a concentration of 1 mM inhibited biofilm
      formation. Aspirin, etodolac, and diclofenac produced the greatest effects, with
      aspirin causing up to 95% inhibition. Celecoxib, nimesulide, ibuprofen, and
      meloxicam also inhibited biofilm formation, but to a lesser extent. Aspirin was
      active against growing and fully mature (48-h) biofilms; its effect was dose
      related, and it produced significant inhibition (20 to 80%) at pharmacological
      concentrations. Simultaneous addition of prostaglandin E(2) abolished the
      inhibitory effect of 25 or 50 micro M aspirin. At 1 mM, aspirin reduced the
      viability of biofilm organisms to 1.9% of that of controls. Surviving cells had a
      wrinkled appearance, as judged by scanning electron microscopy, and consisted of
      both yeasts and hyphae. Treatment with other cyclooxygenase inhibitors, such as
      etodolac, resulted in biofilms that consisted almost entirely of yeast cells. In
      conventional assays for germ tube formation, these drugs produced significant
      inhibition, whereas aspirin had little effect. Our findings suggest that
      cyclooxygenase-dependent synthesis of fungal prostaglandin(s) is important for
      both biofilm development and morphogenesis in C. albicans and may act as a
      regulator in these physiological processes. Our results also demonstrate that
      aspirin possesses potent antibiofilm activity in vitro and could be useful in
      combined therapy with conventional antifungal agents in the management of some
      biofilm-associated Candida infections.

PMID- 14693517
TI  - Modeling antibiotic tolerance in biofilms by accounting for nutrient limitation.
AB  - A mathematical model of biofilm dynamics was used to investigate the protection
      from antibiotic killing that can be afforded to microorganisms in biofilms based
      on a mechanism of localized nutrient limitation and slow growth. The model
      assumed that the rate of killing by the antibiotic was directly proportional to
      the local growth rate. Growth rates in the biofilm were calculated by using the
      local concentration of a single growth-limiting substrate with Monod kinetics.
      The concentration profile of this metabolic substrate was calculated by solving a
      reaction-diffusion problem. The model predicted the following features:
      stratified patterns of growth with zones of no growth in the biofilm interior,
      slow killing of biofilm microorganisms that was further retarded as the initial
      biofilm thickness increased, nonuniform spatial patterns of killing inside the
      biofilm, biofilm killing rates that decrease in a nonlinear way as the
      concentration of the growth-limiting substrate feeding the biofilm is decreased,
      and heightened tolerance when external mass transfer resistance is manifested.
      This modeling study also provides motivation for further investigation of a
      hypothetical cell state in which damaged cells score as nonviable but continue to
      consume substrate. The existence of such a cell state can further retard biofilm
      killing, according to the simulations. The results support the important
      contributions of nutrient limitation and slow growth to the antibiotic tolerance
      of microorganisms in biofilms.

PMID- 14693518
TI  - In vitro activities of the novel cephalosporin LB 11058 against multidrug
      resistant Staphylococci and Streptococci.
AB  - LB 11058 is a novel parenteral cephalosporin with a C-3 pyrimidinyl-substituted
      vinyl sulfide group and a C-7 2-amino-5-chloro-1,3-thiazole group. This study
      evaluated the in vitro activity and spectrum of LB 11058 against 1,245 recent
      clinical isolates, including a subset of gram-positive strains with specific
      resistant phenotypes. LB 11058 was very active against Streptococcus pneumoniae.
      The novel cephalosporin was 8- to 16-fold more potent than ceftriaxone, cefepime,
      or amoxicillin-clavulanate against both penicillin-intermediate and -resistant S.
      pneumoniae. LB 11058 was also very active against both beta-hemolytic
      streptococci (MIC at which 90% of isolates were inhibited [MIC(90)], </=0.008
      micro g/ml) and viridans group streptococci (MIC(90), 0.03 to 0.5 micro g/ml),
      including penicillin-resistant strains. Among oxacillin-susceptible
      Staphylococcus aureus, LB 11058 MIC results varied from 0.06 to 0.25 micro g/ml
      (MIC(50), 0.12 micro g/ml), while among oxacillin-resistant strains LB 11058 MICs
      varied from 0.25 to 1 micro g/ml (MIC(50), 1 micro g/ml). Coagulase-negative
      staphylococci showed an LB 11058 susceptibility pattern similar to that of S.
      aureus, with all isolates being inhibited at </=1 micro g/ml. LB 11058 also
      showed reasonable in vitro activity against Enterococcus faecalis, including
      vancomycin-resistant strains (MIC(50), 1 micro g/ml), and Bacillus spp. (MIC(50),
      0.25 micro g/ml); however, it was less active against Enterococcus faecium
      (MIC(50), >64 micro g/ml) and Corynebacterium spp. (MIC(50), 32 micro g/ml).
      Against gram-negative pathogens, LB 11058 showed activity against Haemophilus
      influenzae (MIC(90), 0.25 to 0.5 micro g/ml) and Moraxella catarrhalis (MIC(90),
      0.25 micro g/ml), with MICs not influenced by beta-lactamase production. In
      conclusion, LB 11058 demonstrated a broad antibacterial spectrum and was highly
      active against gram-positive bacteria, particularly against multidrug-resistant
      staphylococci and streptococci.

PMID- 14693519
TI  - In vivo pharmacodynamic activity of daptomycin.
AB  - Daptomycin is a lipopeptide antibiotic with activity against a wide range of gram
      positive bacteria. We used the neutropenic murine thigh model to characterize the
      pharmacodynamics of daptomycin. ICR/Swiss mice were rendered neutropenic with
      cyclophosphamide; and the thigh muscles of the mice were infected with strains of
      Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecium.
      Animals were treated by subcutaneous injection of daptomycin at doses of 0.20 to
      400 mg/kg of body weight/day divided into one, two, four, or eight doses over 24
      h. Daptomycin exhibited linear pharmacokinetics, with an area under the
      concentration-time curve (AUC) from time zero to infinity/dose of 9.4 and a half
      life of 0.9 to 1.4 h. The level of protein binding was 90%. Free daptomycin
      exhibited concentration-dependent killing and produced in vivo postantibiotic
      effects (PAEs) of 4.8 to 10.8 h. Nonlinear regression analysis was used to
      determine which pharmacokinetic (PK) or pharmacodynamic (PD) parameter was
      important for efficacy by using free drug concentrations. The peak
      concentration/MIC (peak/MIC) ratio and 24-h AUC/MIC ratio were the PK and PD
      parameters that best correlated with in vivo efficacy (R(2) = 83 to 87% for
      peak/MIC and R(2) = 86% for the AUC/MIC ratio, whereas R(2) = 47 to 50% for the
      time that the concentration was greater than the MIC) against standard strains of
      S. aureus and S. pneumoniae. The peak/MIC ratios required for a bacteriostatic
      effect ranged from 12 to 36 for S. pneumoniae, 59 to 94 for S. aureus, and 0.14
      to 0.25 for E. faecium. The AUC/MIC ratios needed for a bacteriostatic effect
      ranged from 75 to 237 for S. pneumoniae, 388 to 537 for S. aureus, and 0.94 to
      1.67 for E. faecium. The free daptomycin concentrations needed to average from
      one to two times the MIC over 24 h to produce a bacteriostatic effect and two to
      four times the MIC over 24 h to produce greater than 99% killing. The long PAE
      and potent bactericidal activity make daptomycin an attractive option for the
      treatment of infections caused by gram-positive bacteria.

PMID- 14693520
TI  - Anti-Trypanosoma cruzi activity of green tea (Camellia sinensis) catechins.
AB  - The trypanocidal action of green tea catechins against two different
      developmental stages of Trypanosoma cruzi is reported for the first time. This
      activity was assayed with the nonproliferative bloodstream trypomastigote and
      with the intracellular replicative amastigote parasite forms. An ethyl acetate
      fraction from Camellia sinensis green tea leaves, which contains most of the
      polyphenolic compounds and the maximal trypanocidal activity, was obtained by
      fractionation of the aqueous extract with organic solvents. The active compounds
      present in this extract were further purified by LH-20 column chromatography and
      were identified by high-performance liquid chromatography analysis with a photo
      diode array detector and gas chromatography coupled to mass spectroscopy. The
      following flavan-3-ols derivatives, known as catechins, were identified:
      catechin, epicatechin, gallocatechin, epigallocatechin, catechin gallate,
      epicatechin gallate, gallocatechin gallate, and epigallocatechin gallate. The
      purified compounds lysed more than 50% of the parasites present in the blood of
      infected BALB/c mice at concentrations as low as 0.12 to 85 pM. The most active
      compounds were gallocatechin gallate and epigallocatechin gallate, with minimal
      bactericidal concentrations that inhibited 50% of isolates tested of 0.12 and
      0.53 pM, respectively. The number of amastigotes in infected Vero cells decreased
      by 50% in the presence of each of these compounds at 100 nM. The effects of the
      catechins on the recombinant T. cruzi arginine kinase, a key enzyme in the energy
      metabolism of the parasite, were assayed. The activity of this enzyme was
      inhibited by about 50% by nanomolar concentrations of catechin gallate or
      gallocatechin gallate, whereas the other members of the group were less
      effective. On the basis of these results, we suggest that these compounds could
      be used to sterilize blood and, eventually, as therapeutic agents for Chagas'
      disease.

PMID- 14693521
TI  - Orally administered targeted recombinant Beta-lactamase prevents ampicillin
      induced selective pressure on the gut microbiota: a novel approach to reducing
      antimicrobial resistance.
AB  - Antibiotics that are excreted into the intestinal tract promote antibiotic
      resistance by exerting selective pressure on the gut microbiota. Using a beagle
      dog model, we show that an orally administered targeted recombinant beta
      lactamase enzyme eliminates the portion of parenteral ampicillin that is excreted
      into the small intestine, preventing ampicillin-induced changes to the fecal
      microbiota without affecting ampicillin levels in serum. In dogs receiving
      ampicillin, significant disruption of the fecal microbiota and the emergence of
      ampicillin-resistant Escherichia coli and TEM genes were observed, whereas in
      dogs treated with ampicillin in combination with an oral beta-lactamase, these
      did not occur. These results suggest a new strategy for reducing antimicrobial
      resistance in humans.

PMID- 14693522
TI  - Efficacy of BB-83698, a novel peptide deformylase inhibitor, in a mouse model of
      pneumococcal pneumonia.
AB  - The efficacy of BB-83698, a novel potent peptide deformylase inhibitor, was
      evaluated in a mouse model of acute pneumonia. The Streptococcus pneumoniae
      isolates tested included four virulent strains (one penicillin-susceptible wild
      type strain, one macrolide-resistant strain, and two quinolone-resistant mutants
      [a mutant carrying mutations in ParC and GyrA and an efflux mutant] isogenic to
      the wild type) and two poorly virulent penicillin-resistant strains. Pneumonia
      was induced by intratracheal inoculation of 10(5) CFU (virulent strains) into
      immunocompetent mice or 10(7) CFU (less virulent strains) into leukopenic mice.
      Animals received three or six subcutaneous injections of antibiotics at 12- or 24
      h intervals, with antibiotic treatment initiated at 3, 6, 12, or 18 h
      postinfection (p.i.). BB-83698 showed potent in vitro activity against all
      strains (MICs, 0.06 to 0.25 micro g/ml). In the in vivo model, all control
      animals died within 2 to 5 days of infection. BB-83698 (80 mg/kg of body weight
      twice daily or 160 mg/kg once daily) protected 70 to 100% of the animals, as
      measured 10 days p.i., regardless of the preexisting resistance mechanisms. In
      contrast, the survival rates for animals treated with the comparator antibiotics
      were 30% for animals treated with erythromycin (100 mg/kg) and infected with the
      macrolide-resistant strain, 34% for animals treated with amoxicillin (200 mg/kg
      every 8 h) and infected with the penicillin-resistant strain, and 0 and 78% for
      animals treated with ciprofloxacin (250 mg/kg) and infected with the ParC and
      GyrA mutant and the efflux mutant, respectively. At 80 mg/kg, BB-83698 generated
      a peak concentration in lung tissue of 61.9 micro g/ml within 1 h and areas under
      the concentration-times curves of 57.4 and 229.4 micro g. h/ml for plasma and
      lung tissue, respectively. The emergence of S. pneumoniae isolates with reduced
      susceptibilities to BB-83698 was not observed following treatment with a
      suboptimal dosing regimen. In conclusion, the potent in vitro activity of BB
      83698 against S. pneumoniae, including resistant strains, translates into good in
      vivo efficacy in a mouse pneumonia model.

PMID- 14693523
TI  - Efficacy of garenoxacin in treatment of experimental endocarditis due to
      Staphylococcus aureus or viridans group streptococci.
AB  - The activity of garenoxacin was investigated in rats with experimental
      endocarditis due to staphylococci and viridans group streptococci (VGS). The
      staphylococci tested comprised one ciprofloxacin-susceptible and methicillin
      susceptible Staphylococcus aureus (MSSA) isolate (isolate 1112), one
      ciprofloxacin-susceptible but methicillin-resistant S. aureus (MRSA) isolate
      (isolate P8), and one ciprofloxacin-resistant mutant (grlA) of P8 (isolate P8-4).
      The VGS tested comprised one penicillin-susceptible isolate and one penicillin
      resistant isolate (Streptococcus oralis 226 and Streptococcus mitis 531,
      respectively). To simulate the kinetics of drugs in humans, rats were infused
      intravenously with garenoxacin every 24 h (peak and trough levels in serum, 6.1
      and 1.0 mg/liter, respectively; area under the concentration-time curve [AUC],
      63.4 mg. h/liter) or levofloxacin every 12 h (peak and trough levels in serum,
      7.3 and 1.5 mg/liter, respectively; AUC, 55.6 mg. h/liter) for 3 or 5 days.
      Flucloxacillin, vancomycin, and ceftriaxone were used as control drugs.
      Garenoxacin, levofloxacin, flucloxacillin, and vancomycin sterilized >/=70% of
      the vegetations infected with both ciprofloxacin-susceptible staphylococcal
      isolates (P < 0.05 versus the results for the controls). Garenoxacin and
      vancomycin also sterilized 70% of the vegetations infected with ciprofloxacin
      resistant MRSA isolate P8-4, whereas treatment with levofloxacin failed against
      this organism (cure rate, 0%; P < 0.05 versus the results obtained with the
      comparator drugs). Garenoxacin did not select for resistant derivatives in vivo.
      In contrast, levofloxacin selected for resistant variants in four of six rats
      infected with MRSA isolate P8-4. Garenoxacin sterilized 90% of the vegetations
      infected with both penicillin-susceptible and penicillin-resistant isolates of
      VGS. Levofloxacin sterilized only 22 and 40% of the vegetations infected with
      penicillin-susceptible S. oralis 226 and penicillin-resistant S. mitis 531,
      respectively. Ceftriaxone sterilized only 40% of those infected with penicillin
      resistant S. mitis 531 (P < 0.05 versus the results obtained with garenoxacin).
      No quinolone-resistant VGS were detected. In all the experiments successful
      quinolone treatment was predicted by specific pharmacodynamic criteria (D. R.
      Andes and W. A. Craig, Clin. Infect. Dis. 27:47-50, 1998). The fact that the
      activity of garenoxacin was equal or superior to those of the standard
      comparators against staphylococci and VGS indicates that it is a potential
      alternative for the treatment of infections caused by such bacteria.

PMID- 14693524
TI  - Immunomodulatory clarithromycin treatment of experimental sepsis and acute
      pyelonephritis caused by multidrug-resistant Pseudomonas aeruginosa.
AB  - Clarithromycin was administered intravenously to 55 rabbits to evaluate its
      effect on experimental sepsis caused by multidrug-resistant Pseudomonas
      aeruginosa. Acute pyelonephritis was induced after ligation of the right ureter
      and injection of 10(8) CFU of the test isolate per kg of body weight into the
      renal pelvis. The animals were divided into six groups: group A, controls; group
      B, rabbits that received one intravenous dose of 80 mg of clarithromycin per kg
      concomitantly with bacterial challenge; group C, rabbits that received two doses
      of clarithromycin, the second one of which was given 2 h after the first one;
      group D, rabbits that received 15 mg of amikacin per kg; group E, rabbits that
      received one dose of clarithromycin and amikacin; and group F, rabbits that
      received two doses of clarithromycin and amikacin. Serum endotoxin levels were
      estimated by the QCL-1000 Limulus amoebocyte lysate assay, tumor necrosis factor
      alpha (TNF-alpha) levels were measured by a bioassay, and malondialdehyde (MDA)
      levels were measured by the thiobarbiturate assay. Viable bacterial counts in
      various tissue samples were also assessed. The mean survival times of the animals
      in groups A, B, C, D, E, and F were 4.50, 7.69, 4.07, 4.55, 11.55, and 11.60
      days, respectively (P = 0.033 for group D versus group F, P = 0.006 for group D
      versus group E, P = not significant for group B versus group E, P = 0.042 for
      group C versus group F). Serum endotoxin levels were similar between groups at
      all sampling times; TNF-alpha and MDA levels in groups B, C, E, and F decreased
      significantly over follow-up. The numbers of viable bacterial cells in the
      infected kidney were similar among the groups; those in the liver, spleen, lungs,
      and mesenteral lymph nodes were significantly decreased in groups B, E, and F
      compared to those in groups A and D. It is concluded that a prolongation of
      survival in animals with experimental sepsis caused by multidrug-resistant P.
      aeruginosa was achieved after coadministration of clarithromycin and amikacin and
      that the increased survival was probably attributable to the immunomodulatory
      properties of clarithromycin.

PMID- 14693525
TI  - Oral delivery of meglumine antimoniate-beta-cyclodextrin complex for treatment of
      leishmaniasis.
AB  - The need for daily parenteral administration represents one of the most serious
      limitations in the clinical use of pentavalent antimonials against leishmaniasis.
      In this work, we investigated the ability of beta-cyclodextrin to enhance the
      oral absorption of antimony and to promote the oral efficacy of meglumine
      antimoniate against experimental cutaneous leishmaniasis. The occurrence of
      interactions between beta-cyclodextrin and meglumine antimoniate was demonstrated
      through the changes induced in the spin lattice relaxation times of protons in
      both compounds. When free and complexed meglumine antimoniate were given orally
      to Swiss mice, plasma antimony levels were found to be about three times higher
      for the meglumine antimoniate-beta-cyclodextrin complex than for the free drug.
      Antileishmanial efficacy was evaluated in BALB/c mice experimentally infected
      with Leishmania amazonensis. Animals treated daily with the complex (32 mg of
      Sb/kg of body weight) by the oral route developed significantly smaller lesions
      than those treated with meglumine antimoniate (120 mg of Sb/kg) and control
      animals (treated with saline). The effectiveness of the complex given orally was
      equivalent to that of meglumine antimoniate given intraperitoneally at a twofold
      higher antimony dose. The antileishmanial efficacy of the complex was confirmed
      by the significantly lower parasite load in the lesions of treated animals than
      in saline-treated controls. This work reports for the first time the
      effectiveness of an oral formulation for pentavalent antimonials.

PMID- 14693526
TI  - Sensitive enzyme immunoassay for measuring plasma and intracellular nevirapine
      levels in human immunodeficiency virus-infected patients.
AB  - We have developed an enzyme immunoassay to measure nevirapine (NVP) in plasma and
      peripheral blood mononuclear cells. Anti-NVP polyclonal antibodies were raised in
      rabbits by using a synthetic NVP derivative coupled to keyhole limpet hemocyanin
      as the immunogen, and the enzyme tracer was prepared by chemically coupling the
      NVP derivative with acetylcholinesterase. These reagents were used to develop a
      sensitive competitive enzyme immunoassay performed in microtitration plates with
      a 100-pg ml(-1) limit of detection and thus approximately 100 times more
      sensitive than previously published techniques. The plasma assay was performed
      directly without extraction (in this case, a 500-pg ml(-1) limit of detection was
      observed) on a minimum of 30 micro l of plasma. This assay shows good precision
      and efficiency, since recovery from human plasma and cell extracts spiked with
      NVP ranged between 87 and 104%, with coefficients of variation of <10%. A
      pharmacokinetic analysis of plasma NVP was performed for seven patients infected
      with human immunodeficiency virus (HIV), and it gave results similar to published
      findings. Intracellular concentrations of NVP were measured in cultured human T
      lymphoblastoid cells and peripheral blood mononuclear cells from HIV-infected
      patients. The results indicated a very low intracellular/extracellular
      concentration ratio (0.134), thus demonstrating the absence of intracellular drug
      accumulation. This is the first intracellular assay of a nonnucleoside reverse
      transcriptase inhibitor, and this method could be useful in monitoring plasma and
      intracellular NVP levels in HIV-infected patients.

PMID- 14693527
TI  - Human salivary histatin 5 fungicidal action does not induce programmed cell death
      pathways in Candida albicans.
AB  - Salivary histatins (Hsts) are potent candidacidal proteins that induce a nonlytic
      form of cell death in Candida albicans accompanied by loss of mean cell volume,
      cell cycle arrest, and elevation of intracellular levels of reactive oxygen
      species (ROS). Since these phenotypes are often markers of programmed cell death
      and apoptosis, we investigated whether other classical markers of apoptosis,
      including generation of intracellular ROS and protein carbonyl groups,
      chromosomal fragmentation (laddering), and cytochrome c release, are found in Hst
      5-mediated cell death. Increased intracellular levels of ROS in C. albicans were
      detected in cells both following exogenous application of Hst 5 and following
      intracellular expression of Hst 5. However, Western blot analysis failed to
      detect specifically increased protein carbonylation in Hst 5-treated cells. There
      was no evidence of chromosomal laddering and no cytochrome c release was observed
      following treatment of C. albicans mitochondria with Hst 5. Superoxide dismutase
      enzymes of C. albicans and Saccharomyces cerevisiae provide essential protection
      against oxidative stress; therefore, we tested whether SOD mutants have increased
      susceptibility to Hst 5, as expected if ROS mediate fungicidal effects. Cell
      survival of S. cerevisiae SOD1/SOD2 mutants and C. albicans SOD1 mutants
      following Hst 5 treatment (31 micro M) was indistinguishable from the survival of
      wild-type cells treated with Hst 5. We conclude that ROS may not play a direct
      role in fungicidal activity and that Hst 5 does not initiate apoptosis or
      programmed cell death pathways.

PMID- 14693528
TI  - Six-week randomized controlled trial to compare the tolerabilities,
      pharmacokinetics, and antiviral activities of GW433908 and amprenavir in human
      immunodeficiency virus type 1-infected patients.
AB  - This study compared the plasma amprenavir pharmacokinetics of the human
      immunodeficiency virus (HIV) protease inhibitors amprenavir (Agenerase) 1,200 mg
      twice daily (BID) and the amprenavir prodrug GW433908, a formulation that
      substantially reduces the number of tablets per dose compared with amprenavir, at
      doses of 1,395 mg and 1,860 mg BID, in combination with abacavir 300 mg BID and
      lamivudine 150 mg BID in patients with HIV infection. Overall, 78 patients
      received study treatment. Compared with amprenavir 1,200 mg BID, both GW433908
      1,395 mg BID and GW433908 1,860 mg BID delivered equivalent steady-state (ss)
      values for area under the plasma amprenavir concentration-time curve (AUC) at the
      end of a dosing interval (tau), lower maximum plasma amprenavir concentrations
      (30% lower), and higher plasma amprenavir concentrations at the end of a dosing
      interval (28% higher for GW433908 1,395 mg BID and 46% higher for GW433908 1,860
      mg BID). Time-variant plasma amprenavir pharmacokinetics were observed with
      reductions in plasma amprenavir exposure over the first 4 weeks of dosing; the
      decrease in plasma amprenavir AUC(tau,ss) versus the AUC from 0 h to infinity was
      27% for GW43308 1,395 mg, 45% for GW433908 1,860 mg, and 23% for amprenavir 1,200
      mg. All three regimens reduced plasma HIV-1 RNA ( approximately 2 log(10)
      copies/ml) and increased CD4(+) cell counts ( approximately 100 cells/mm(3)) over
      the initial 28 days. Adverse event profiles were consistent with those previously
      reported for amprenavir. Although not statistically tested, the GW433908 groups
      appeared to have fewer gastrointestinal symptoms. In conclusion, the protease
      inhibitor GW433908 delivered comparable plasma amprenavir concentrations to those
      delivered by amprenavir 1,200 mg BID. GW433908, in combination with abacavir and
      lamivudine, demonstrated potent antiviral activity and was generally well
      tolerated over a 4-week period.

PMID- 14693529
TI  - Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in
      human immunodeficiency virus-infected children.
AB  - Tenofovir disoproxil fumarate (DF) is a potent nucleotide analog reverse
      transcriptase inhibitor approved for the treatment of human immunodeficiency
      virus (HIV)-infected adults. The single-dose and steady-state pharmacokinetics of
      tenofovir were evaluated following administration of tenofovir DF in treatment
      experienced HIV-infected children requiring a change in antiretroviral therapy.
      Using increments of tenofovir DF 75-mg tablets, the target dose was 175 mg/m(2);
      the median administered dose was 208 mg/m(2). Single-dose pharmacokinetics were
      evaluated in 18 subjects, and the geometric mean area under the concentration
      time curve from 0 h to infinity (AUC(0- infinity )) was 2,150 ng. h/ml and the
      geometric mean maximum concentration (C(max)) was 266 ng/ml. Subsequently, other
      antiretrovirals were added to each patient's regimen based upon treatment history
      and baseline viral resistance results. Steady-state pharmacokinetics were
      evaluated in 16 subjects at week 4. The steady-state, geometric mean AUC for the
      24-h dosing interval was 2,920 ng. h/ml and was significantly higher than the
      AUC(0- infinity ) after the first dose (P = 0.0004). The geometric mean C(max) at
      steady state was 302 ng/ml. Tenofovir DF was generally very well tolerated.
      Steady-state tenofovir exposures in children receiving tenofovir DF-containing
      combination antiretroviral therapy approached values seen in HIV-infected adults
      (AUC, approximately 3,000 ng. h/ml; C(max), approximately 300 ng/ml) treated with
      tenofovir DF at 300 mg.

PMID- 14693530
TI  - In vitro and in vivo activities of a triterpenoid saponin extract (PX-6518) from
      the plant Maesa balansae against visceral leishmania species.
AB  - The in vitro and in vivo activities of a mixture of six oleane triterpene
      saponins, recovered from the methanolic extract of the leaves of the Vietnamese
      plant Maesa balansae (PX-6518), were evaluated against drug-sensitive visceral
      Leishmania strains. The in vitro 50% inhibitory concentration (IC(50)) against
      intracellular Leishmania infantum amastigotes was 0.04 micro g/ml. The cytotoxic
      concentrations causing 50% cell death (CC(50)s) were about 1 micro g/ml in murine
      macrophage host cells and >32 micro g/ml in human fibroblasts (MRC-5 cell line).
      Evaluation in the Leishmania donovani BALB/c mouse model indicated that a single
      subcutaneous administration of 0.4 mg/kg at 1 day after infection reduced liver
      amastigote burdens by about 95% in all treated animals. If treatment was delayed
      until 14 days after infection, a dose of 1.6 mg/kg of body weight was required to
      maintain the same level of activity. Single 250-mg/kg doses of sodium
      stibogluconate (Pentostam) 1 and 14 days after infection produced comparable
      efficacies. A single dose of PX-6518 at 2.5 mg/kg administered 5 days before
      infection was still 100% effective in preventing liver infection, suggesting a
      particularly long residual action. Spleen and bone marrow could not be cleared by
      PX-6518 nor sodium stibogluconate. PX-6518 did not show activity after oral
      dosing at up to 200 mg/kg for 5 days. This study concludes that triterpenoid
      saponins from M. balansae show promising in vitro and in vivo antileishmanial
      potential and can be considered as new lead structures in the search for novel
      antileishmanial drugs.

PMID- 14693531
TI  - Pharmacodynamics of a new triazole, posaconazole, in a murine model of
      disseminated candidiasis.
AB  - Previous in vivo studies have characterized the pharmacodynamic characteristics
      of two triazole compounds, fluconazole and ravuconazole. These investigations
      demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC
      ratio is the critical pharmacokinetic-pharmacodynamic (PK-PD) parameter
      associated with treatment efficacy. Further analysis demonstrated that a free
      drug triazole 24-h AUC/MIC ratio of 20 to 25 was predictive of treatment success
      in both experimental models and clinical trials. We used a neutropenic murine
      model of disseminated Candida albicans infection to similarly characterize the
      time course activity of the new triazole, posaconazole. The PK-PD parameters
      (percent time above MIC, AUC/MIC ratio, and peak serum drug level/MIC ratio) were
      correlated with in vivo efficacy, as measured by organism number in kidney
      cultures after 48 h of therapy. Kinetics and protein binding following oral
      posaconazole dosing were performed in neutropenic infected mice. Peak levels and
      AUC from 0 h to infinity values were nonlinear over the 16-fold dose range
      studied. Serum drug elimination half-life ranged from 12.0 to 17.7 h. Protein
      binding was 99%. Single dose postantifungal effect studies demonstrated prolonged
      suppression of organism regrowth after serum posaconazole levels had fallen below
      the MIC. Treatment efficacy with the four dosing intervals studied was similar,
      supporting the AUC/MIC ratio as the PK-PD parameter predictive of efficacy.
      Nonlinear regression analysis also suggested that the AUC/MIC ratio was strongly
      predictive of treatment outcomes (AUC/MIC ratio R(2) = 83%; peak serum drug/MIC
      ratio R(2) = 85%; time that serum levels of posaconazole remained above the MIC
      R(2) = 65%). Similar studies were conducted with 11 additional C. albicans
      isolates with various posaconazole susceptibilities (MIC, 0.015 to 0.12 micro
      g/ml) to determine if a similar 24-h AUC/MIC ratio was associated with efficacy.
      The posaconazole free-drug AUC/MIC ratios were similar for all of the organisms
      studied (6.12 to 26.7, mean +/- SD = 16.9 +/- 7.8, P value, 0.42). These free
      drug AUC/MIC ratios are similar to those observed for other triazoles in this
      model.

PMID- 14693532
TI  - Molecular basis of intrinsic macrolide resistance in the Mycobacterium
      tuberculosis complex.
AB  - The intrinsic resistance of the Mycobacterium tuberculosis complex (MTC) to most
      antibiotics, including macrolides, is generally attributed to the low
      permeability of the mycobacterial cell wall. However, nontuberculous mycobacteria
      (NTM) are much more sensitive to macrolides than members of the MTC. A search for
      macrolide resistance determinants within the genome of M. tuberculosis revealed
      the presence of a sequence encoding a putative rRNA methyltransferase. The
      deduced protein is similar to Erm methyltransferases, which confer macrolide
      lincosamide-streptogramin (MLS) resistance by methylation of 23S rRNA, and was
      named ErmMT. The corresponding gene, ermMT (erm37), is present in all members of
      the MTC but is absent in NTM species. Part of ermMT is deleted in some vaccine
      strains of Mycobacterium bovis BCG, such as the Pasteur strain, which lack the
      RD2 region. The Pasteur strain was susceptible to MLS antibiotics, whereas MTC
      species harboring the RD2 region were resistant to them. The expression of ermMT
      in the macrolide-sensitive Mycobacterium smegmatis and BCG Pasteur conferred MLS
      resistance. The resistance patterns and ribosomal affinity for erythromycin of
      Mycobacterium host strains expressing ermMT, srmA (monomethyltransferase from
      Streptomyces ambofaciens), and ermE (dimethyltransferase from Saccharopolyspora
      erythraea) were compared, and the ones conferred by ErmMT were similar to those
      conferred by SrmA, corresponding to the MLS type I phenotype. These results
      suggest that ermMT plays a major role in the intrinsic macrolide resistance of
      members of the MTC and could be the first example of a gene conferring resistance
      by target modification in mycobacteria.

PMID- 14693533
TI  - Biofilm formation by Stenotrophomonas maltophilia: modulation by quinolones,
      trimethoprim-sulfamethoxazole, and ceftazidime.
AB  - We investigated the in vitro effects of seven fluoroquinolones (ciprofloxacin,
      grepafloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, and
      rufloxacin), compared to those of trimethoprim-sulfamethoxazole (SXT) and
      ceftazidime on total biomass and cell viability of Stenotrophomonas maltophilia
      biofilm. S. maltophilia attached rapidly to polystyrene, within 2 h of
      incubation, and then biofilm formation increased over time, reaching maximum
      growth at 24 h. In the presence of fluoroquinolones at one-half and one-fourth
      the MIC, biofilm biomass was significantly (P < 0.01) reduced to 55 to 70% and 66
      to 76% of original mass, respectively. Ceftazidime and SXT did not exert any
      activity. Biofilm bacterial viability was significantly reduced by all
      antibiotics tested at one-half the MIC. At one-fourth the MIC all antibiotics,
      except levofloxacin, significantly reduced viability. Treatment of preformed
      biofilms with bactericidal concentrations (500, 100, and 50 micro g/ml) of all
      fluoroquinolones caused, except for norfloxacin, significant reduction of biofilm
      biomass to 29.5 to 78.8, 64.1 to 83.6, and 70.5 to 82.8% of original mass,
      respectively. SXT exerted significant activity at 500 micro g/ml only.
      Ceftazidime was completely inactive. Rufloxacin exhibited the highest activity on
      preformed biofilm viability, significantly decreasing viable counts by 0.6, 5.4,
      and 17.1% at 500, 100, and 50 micro g/ml, respectively. Our results show that (i)
      subinhibitory (one-half and one-fourth the MIC) concentrations of
      fluoroquinolones inhibit adherence of S. maltophilia to polystyrene and (ii)
      clinically achievable concentrations (50 and 100 micro g/ml) of rufloxacin are
      able to eradicate preformed S. maltophilia biofilm.

PMID- 14693534
TI  - Fungicidal activity of fluconazole against Candida albicans in a synthetic vagina
      simulative medium.
AB  - Fluconazole (FLZ) has emerged as a highly successful agent in the management of
      systemic infections of Candida. Cure rates for symptomatic candidiasis following
      single 150-mg FLZ dose therapy exceed 90%. In vitro, however, FLZ is fungistatic
      only in a narrow pH range and is not effective at vaginal pH, 4.2. This study
      evaluated the effect of FLZ on Candida albicans under in vitro conditions
      resembling the vaginal microenvironment, using vagina-simulative medium (VS). We
      found that FLZ was fungicidal for C. albicans in VS, but not in other media at
      the same pH, 4.2. In VS, FLZ was fungicidal at concentrations of >/=8 micro g/ml
      and reduced viability by greater than 99.9%. Analysis of the components of VS
      indicated that 17 mM acetic acid, a concentration achieved in the vagina, was
      responsible for the synergistic, fungicidal effect. This effect was not seen at
      neutral pH. Other substrates were not effective substitutes for acetic acid;
      however, short-chained carboxylic acids, glyoxylate and malonate, were effective.
      Most strains of C. albicans that were resistant to FLZ under standard conditions
      were killed by FLZ plus acetate. Other species of Candida were also killed,
      except C. krusei and C. glabrata. This study shows that FLZ has fungicidal
      activity for Candida species under in vitro conditions that mimic the vaginal
      microenvironment. This raises the possibility that FLZ may also have fungicidal
      effects during treatment of vaginal candidiasis. Elucidating the mechanism by
      which FLZ and acetate interact may disclose vulnerable pathways that could be
      exploited in drug development.

PMID- 14693535
TI  - Antimicrobial susceptibility and synergy studies of Stenotrophomonas maltophilia
      isolates from patients with cystic fibrosis.
AB  - Stenotrophomonas maltophilia is a newly emerging pathogen being detected with
      increasing frequency in patients with cystic fibrosis (CF). The impact of this
      multidrug-resistant organism on lung function is uncertain. The optimal treatment
      for S. maltophilia in CF patients is unknown. We studied the in vitro activity of
      ten antimicrobial agents, and conducted synergy studies by using checkerboard
      dilutions of eight pairs of antimicrobial agents against strains isolated from
      673 CF patients from 1996 to 2001. This represents approximately 7 to 23% of the
      CF patients in the United States who harbor S. maltophilia annually. Doxycycline
      was the most active agent and inhibited 80% of 673 initial patient isolates,
      while trimethoprim-sulfamethoxazole inhibited only 16%. High concentrations of
      colistin proved more active than high concentrations of tobramycin and
      gentamicin. Serial isolates (n = 151) from individual patients over time (median,
      290 days) showed minimal changes in resistance. Synergistic or additive activity
      was demonstrated by trimethoprim-sulfamethoxazole paired with ticarcillin
      clavulanate (65% of strains), ciprofloxacin paired with ticarcillin-clavulanate
      (64% of strains), ciprofloxacin paired with piperacillin-tazobactam (59% of
      strains), trimethoprim-sulfamethoxazole paired with piperacillin-tazobactam (55%
      of strains), and doxycycline paired with ticarcillin-clavulanate (49% of
      strains). In all, 522 (78%) isolates were multidrug resistant (i.e., resistant to
      all agents in two or more antimicrobial classes) but 473 (91%) of these were
      inhibited by at least one antimicrobial combination (median, four; range, one to
      eight). To determine appropriate treatment for patients with CF, it is important
      to monitor the prevalence, antimicrobial susceptibility, and clinical impact of
      S. maltophilia in this patient population.

PMID- 14693536
TI  - Evolution of human immunodeficiency virus type 1 (HIV-1) resistance mutations in
      nonnucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1-infected
      patients switched to antiretroviral therapy without NNRTIs.
AB  - We studied the evolution of nonnucleoside reverse transcriptase inhibitor (NNRTI)
      resistance mutations among 29 human immunodeficiency virus type 1 (HIV-1)
      infected patients who experienced virologic failure when receiving an NNRTI
      containing regimen (nevirapine, delavirdine, or efavirenz) and subsequently
      switched to antiretroviral therapy without NNRTIs. Genotypic resistance was
      determined from plasma samples collected at the time of NNRTI withdrawal
      (baseline) and during follow-up. At baseline, 83% of patients had more than two
      thymidine analog resistance mutations (TAMs), and all had NNRTI resistance
      mutations. Mutations at codons 103, 181, and 190 were found in 62, 62, and 34% of
      the patients, respectively. Follow-up samples were available after a median time
      of 6 months in all patients and at 12 months in 22 patients. The mean number of
      resistance mutations to NNRTIs was significantly lower at months 6 (1.34 +/-
      1.04) and 12 (1.18 +/- 1.05) than at month 0 (2.03 +/- 1.02) (P < 0.009). The
      percentages of patients with at least one NNRTI resistance mutation were 100, 76,
      and 73% at baseline, month 6, and month 12, respectively (P < 0.0044). Overall,
      70% of the patients had a mutation at codon 103 or 181 at month 12. The mean
      number of TAMs did not vary significantly during follow-up. Our data show that,
      in the context of maintained antiretroviral therapy, NNRTI resistance mutations
      persist in two-thirds of the patients in spite of NNRTI withdrawal. These results
      argue for the low impact of NNRTI resistance mutations on viral fitness and
      suggest that resistance mutations to different classes of drugs are associated on
      the same genome, at least in some of the resistant strains.

PMID- 14693537
TI  - Equivalent steady-state pharmacokinetics of lamivudine in plasma and lamivudine
      triphosphate within cells following administration of lamivudine at 300
      milligrams once daily and 150 milligrams twice daily.
AB  - Once-daily administration of 300 mg of lamivudine in combination with other
      antiretroviral agents has been proposed as a possible way to optimize anti-human
      immunodeficiency virus (HIV) treatment and to facilitate adherence. A single
      center, randomized, two-way, crossover study was conducted in 60 healthy subjects
      to compare the steady-state pharmacokinetics of lamivudine in plasma and its
      putative active anabolite, lamivudine 5'-triphosphate (lamivudine-TP), in
      peripheral blood mononuclear cells (PBMCs) following 7 days of treatment with
      lamivudine at 300 mg once daily and 7 days of the standard regimen of 150 mg
      twice daily. Serial blood samples were collected over 24 h for determination of
      plasma lamivudine concentrations by liquid chromatography-mass spectrometry and
      intracellular lamivudine-TP concentrations in peripheral blood mononuclear cells
      by high-performance liquid chromatography/radioimmunoassay methods.
      Pharmacokinetic parameters were calculated based on lamivudine and lamivudine-TP
      concentration-time data. Regimens were considered bioequivalent if 90% confidence
      intervals (CI) for the ratio (once daily/twice daily) of geometric least-squares
      (GLS) means for lamivudine and lamivudine-TP pharmacokinetic values fell within
      the acceptance range of 0.8 to 1.25. Steady-state plasma lamivudine
      pharmacokinetics following the once- and twice-daily regimens were bioequivalent
      with respect to the area under the drug concentration-time curve from 0 to 24 h
      at steady state (AUC(24,ss)) (GLS mean ratio, 0.94; 90% CI, 0.92, 0.97) and
      average plasma lamivudine concentration over the dosing interval (C(ave,ss)) (GLS
      mean ratio, 0.94; 90% CI, 0.92, 0.97). Steady-state intracellular lamivudine-TP
      pharmacokinetics after the once- and twice-daily regimens were bioequivalent with
      respect to AUC(24,ss) (GLS mean ratio, 0.99; 90% CI, 0.88, 1.11), C(ave,ss) (GLS
      mean ratio, 0.99; 90% CI, 0.88, 1.11), and maximum lamivudine concentration
      (C(max,ss)) (GLS mean ratio, 0.93; 90% CI, 0.81, 1.07). Lamivudine-TP trough
      concentrations were modestly lower (by 18 to 24%) during the once-daily regimen;
      the clinical importance of this is unclear, given the large intersubject
      variability in values that was observed (coefficient of variation, 48 to 124%).
      Once-daily lamivudine was as well tolerated as the twice-daily regimen. Overall,
      the results of this study suggest that for key AUC-related parameters, lamivudine
      at 300 mg once daily is pharmacokinetically equivalent to lamivudine at 150 mg
      twice daily.

PMID- 14693538
TI  - Pharmacokinetics and safety of single oral doses of emtricitabine in human
      immunodeficiency virus-infected children.
AB  - Emtricitabine (FTC; Emtriva), a potent deoxycytidine nucleoside reverse
      transcriptase inhibitor, has recently been approved by the U.S. Food and Drug
      Administration for the treatment of human immunodeficiency virus (HIV) infection.
      In adults, FTC has demonstrated linear kinetics over a wide dose range, and FTC
      200 mg once a day (QD) is the recommended therapeutic dose. A phase I open-label
      trial was conducted in children to identify an FTC dosing regimen that would
      provide comparable plasma exposure to that observed in adults at 200 mg QD. Two
      single oral doses of FTC (60 and 120 mg/m(2), up to a maximum of 200 mg, in
      solutions) were evaluated in HIV-infected children aged <18 years old. Children
      >/=6 years old also received a third dose of approximately 120 mg/m(2) in
      capsules. A total of 25 children (two <2 years old, eight 2 to 5 years old, eight
      6 to 12 years old, and seven 13 to 17 years old) received at least two doses of
      FTC. Single escalating oral doses of FTC were well tolerated and produced dose
      proportional plasma drug concentrations in children. The FTC pharmacokinetics was
      comparable between adults and children 22 months to 17 years of age. The capsule
      formulation provided approximately 20% higher plasma FTC exposure than the
      solution formulation. Using plasma area under the concentration-time curve (AUC)
      data at the 120-mg/m(2) dose, it is projected (based on dose proportionality)
      that a 6-mg/kg dose (up to a maximum of 200 mg) of FTC would produce plasma AUCs
      in children comparable to those in adults given a 200-mg dose (i.e., median of
      approximately 10 h. micro g/ml). This pediatric FTC dose is being evaluated in
      long-term phase II therapeutic trials in HIV-infected children.

PMID- 14693539
TI  - Five additional genes are involved in clavulanic acid biosynthesis in
      Streptomyces clavuligerus.
AB  - An approximately 12.5-kbp region of DNA sequence from beyond the end of the
      previously described clavulanic acid gene cluster was analyzed and found to
      encode nine possible open reading frames (ORFs). Involvement of these ORFs in
      clavulanic acid biosynthesis was assessed by creating mutants with defects in
      each of the ORFs. orf12 and orf14 had been previously reported to be involved in
      clavulanic acid biosynthesis. Now five additional ORFs are shown to play a role,
      since their mutation results in a significant decrease or total absence of
      clavulanic acid production. Most of these newly described ORFs encode proteins
      with little similarity to others in the databases, and so their roles in
      clavulanic acid biosynthesis are unclear. Mutation of two of the ORFs, orf15 and
      orf16, results in the accumulation of a new metabolite, N-acetylglycylclavaminic
      acid, in place of clavulanic acid. orf18 and orf19 encode apparent penicillin
      binding proteins, and while mutations in these genes have minimal effects on
      clavulanic acid production, their normal roles as cell wall biosynthetic enzymes
      and as targets for beta-lactam antibiotics, together with their clustered
      location, suggest that they are part of the clavulanic acid gene cluster.

PMID- 14693540
TI  - In vitro pharmacodynamic activities of ABT-492, a novel quinolone, compared to
      those of levofloxacin against Streptococcus pneumoniae, Haemophilus influenzae,
      and Moraxella catarrhalis.
AB  - ABT-492 is a novel quinolone with potent activity against gram-positive, gram
      negative, and atypical pathogens, making this compound an ideal candidate for the
      treatment of community-acquired pneumonia. We therefore compared the in vitro
      pharmacodynamic activity of ABT-492 to that of levofloxacin, an antibiotic
      commonly used for the treatment of pneumonia, through MIC determination and time
      kill kinetic analysis. ABT-492 demonstrated potent activity against penicillin
      sensitive, penicillin-resistant, and levofloxacin-resistant Streptococcus
      pneumoniae strains (MICs ranging from 0.0078 to 0.125 micro g/ml); beta-lactamase
      positive and beta-lactamase-negative Haemophilus influenzae strains (MICs ranging
      from 0.000313 to 0.00125 micro g/ml); and beta-lactamase-positive and beta
      lactamase-negative Moraxella catarrhalis strains (MICs ranging from 0.001 to
      0.0025 micro g/ml), with MICs being much lower than those of levofloxacin. Both
      ABT-492 and levofloxacin demonstrated concentration-dependent bactericidal
      activities in time-kill kinetics studies at four and eight times the MIC with 10
      of 12 bacterial isolates exposed to ABT-492 and with 12 of 12 bacterial isolates
      exposed to levofloxacin. Sigmoidal maximal-effect models support concentration
      dependent bactericidal activity. The model predicts that 50% of maximal activity
      can be achieved with concentrations ranging from one to two times the MIC for
      both ABT-492 and levofloxacin and that near-maximal activity (90% effective
      concentration) can be achieved at concentrations ranging from two to five times
      the MIC for ABT-492 and one to six times the MIC for levofloxacin.

PMID- 14693541
TI  - Constitutive expression of a chromosomal class A (BJM group 2) beta-lactamase in
      Xanthomonas campestris.
AB  - Sequencing of the upstream region of the beta-lactamase gene from Xanthomonas
      campestris pv. campestris 11 (bla(XCC-1)) revealed the cognate ampR1 gene (289
      amino acids, 31 kDa). It runs divergently from bla(XCC-1) with a 100-bp
      intergenic region (IG) containing partially overlapped promoters with structural
      features typical of the bla-ampR IG. The deduced AmpR1 protein shows significant
      identity in amino acid sequence and conserved motifs with AmpR proteins of other
      species, e.g., of Pseudomonas aeruginosa (58.2% amino acid identity). Results of
      insertional mutation, complementation tests, and beta-lactamase assays suggested
      that expression of bla(XCC-1) was constitutive and dependent on AmpR1. Four bla
      genes and two ampR genes are present in the fully sequenced X. campestris pv.
      campestris ATCC 33913 genome, with XCC3039 and XCC3040 considered the analogues
      of bla(XCC-1) and ampR1, respectively. An ampR1 homologue was detected by
      Southern hybridization in the ampicillin-resistant Xanthomonas strains, which
      appear to express beta-lactamase constitutively. Although the significance
      remains to be studied, constitutive expression of beta-lactamase by a widespread
      bacterial genus raises environmental concerns regarding the dissemination of
      resistance genes.

PMID- 14693542
TI  - Intracutaneous distributions of fluconazole, itraconazole, and griseofulvin in
      Guinea pigs and binding to human stratum corneum.
AB  - We have compared the distribution of fluconazole (FLC) with that of itraconazole
      (ITC) and griseofulvin (GRF) in the abdominal skin tissues after a single oral
      dose was administered to guinea pigs. The FLC concentrations in the stratum
      corneum reached a peak at 2 h after administration and were similar to those of
      ITC and higher than those of GRF in spite of the administration of a lower dose.
      GRF was eliminated from the stratum corneum faster than FLC and ITC. The FLC
      concentrations were also remarkably higher than those of ITC and GRF in the
      epidermis-cutis but lower in the subcutaneous fatty tissue. The distribution
      characteristics of each drug result from differences in their physicochemical
      properties. Following the administration of multiple doses, the FLC
      concentrations in the stratum corneum were highest in the abdominal skin tissues;
      those at 24 h after each administration increased gradually and were maintained
      at a level more than 10 times higher than that of the plasma concentrations. The
      FLC concentrations in the planta pedis stratum corneum and in the nail showed
      good dose proportionality and obvious accumulation and were 60 and 40 times as
      high as that in plasma on day 14. The extent of binding of FLC to human corneous
      keratin in vitro was about 10%, which is lower than those of ITC (94 to 97%) and
      GRF (36 to 38%). FLC, unlike ITC, therefore, is presumed to exist in the stratum
      corneum at high concentrations in an active nonbinding form. These excellent
      intracutaneous pharmacokinetic properties of FLC probably account in large part
      for the in vivo efficacy of FLC.

PMID- 14693543
TI  - Risk factors for acquisition of imipenem-resistant Acinetobacter baumannii: a
      case-control study.
AB  - Risk factors for the nosocomial occurrence of imipenem-resistant Acinetobacter
      baumannii (IRAB) were determined. A case-control study design was used for a
      comparison of two groups of A. baumannii-positive patients with control patients.
      Nosocomial IRAB was isolated from the first group of A. baumannii-positive
      patients, and imipenem-susceptible A. baumannii (ISAB) was isolated from the
      second group. The control patients were randomly selected in a 4:1 ratio from the
      same medical or surgical services from which the A. baumannii-positive patients
      were receiving care when the isolation of IRAB occurred. Risk factors analyzed
      included demographic variables, comorbid conditions, variables related to
      hospitalization, and the antimicrobials used. IRAB was isolated from 104
      patients, and ISAB was isolated from 387 patients between January and December
      2000. The risk factors for IRAB were a previous intensive care unit (ICU) stay
      (odds ratio [OR], 21.54; 95% confidence interval [CI], 10.73 to 43.23) and prior
      exposure to imipenem (OR, 9.18; 95% CI, 3.99 to 21.13) or third-generation
      cephalosporins (OR, 2.11; 95% CI, 1.13 to 3.95). Risk factors for ISAB were a
      previous ICU stay (OR, 8.05; 95% CI, 5.67 to 11.44) and exposure to third
      generation cephalosporins (OR, 2.07; 95% CI, 1.47 to 2.91). Our results suggest
      that the nosocomial occurrence of IRAB or ISAB is strongly related to an ICU
      stay, and IRAB occurrence may be favored by the selection pressure of imipenem.

PMID- 14693544
TI  - Antimicrobial activity of a chelatable poly(arginyl-histidine) produced by the
      ergot fungus Verticillium kibiense.
AB  - We have recently developed a convenient method of screening a broad range of
      microorganisms that produce epsilon-poly-L-lysine (M. Nishikawa and K. Ogawa,
      Appl. Environ. Microbiol. 68:3575-3581, 2002). Using this method, we found an
      ergot fungus that secretes a charged polypeptide other than epsilon-poly-L
      lysine. It was identified as a new species on the basis of its 28S rRNA sequence
      and was named Verticillium kibiense (formerly Epichloe kibiensis). Peptide
      sequencing and mass spectrometry revealed that the polypeptide is a linear
      peptide composed of repeated units of arginyl-histidine. The numbers of repeated
      units were in most cases five and in some cases four or six. This peptide showed
      activity against a broad range of bacteria and fungi but lost its activity under
      conditions of high ionic strength. Zinc and copper ions specifically changed the
      circular dichroism spectra of the peptide and restored the antimicrobial activity
      from abrogation under high ionic conditions, although these ions had no
      reinforcing effect on antimicrobial activity when they were added to solutions at
      a low ionic strength. The peptide labeled with fluorescein was able to permeate
      the cell membranes of target microbes, but its ability to permeate cell membranes
      decreased under conditions of high ionic strength. This decreased ability was
      partially recovered specifically by the addition of zinc and copper ions. These
      results indicate that poly(arginyl-histidine) is a cationic polypeptide
      characterized by specific metal binding and resistance to salts.

PMID- 14693545
TI  - Growth-inhibitory effect of heparin on Babesia parasites.
AB  - We examined the inhibitory effects of three heparins on the growth of Babesia
      parasites. The multiplication of Babesia bovis, B. bigemina, B. equi, and B.
      caballi in in vitro cultures and that of B. microti in vivo were significantly
      inhibited in the presence of heparins, as determined by light microscopy.
      Treatment with various concentrations of heparin showed complete clearance of the
      intracellular parasites. Interestingly, a higher percentage of abnormally
      multidividing B. bovis parasites was observed in the presence of low
      concentrations of heparin. Furthermore, fluorescein isothiocyanate-labeled
      heparin was preferably found on the surfaces of extracellular merozoites, as
      detected by confocal laser scanning microscopy. These findings indicate that the
      heparin covers the surfaces of babesial merozoites and inhibits their subsequent
      invasion of erythrocytes.

PMID- 14693546
TI  - In vitro inhibition of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier
      protein reductase MabA by isoniazid.
AB  - The first-line specific antituberculous drug isoniazid inhibits the fatty acid
      elongation system (FAS) FAS-II involved in the biosynthesis of mycolic acids,
      which are major lipids of the mycobacterial envelope. The MabA protein that
      catalyzes the second step of the FAS-II elongation cycle is structurally and
      functionally related to the in vivo target of isoniazid, InhA, an NADH-dependent
      enoyl-acyl carrier protein reductase. The present work shows that the NADPH
      dependent beta-ketoacyl reduction activity of MabA is efficiently inhibited by
      isoniazid in vitro by a mechanism similar to that by which isoniazid inhibits
      InhA activity. It involves the formation of a covalent adduct between Mn(III)
      activated isoniazid and the MabA cofactor. Liquid chromatography-mass
      spectrometry analyses revealed that the isonicotinoyl-NADP adduct has multiple
      chemical forms in dynamic equilibrium. Both kinetic experiments with isolated
      forms and purification of the enzyme-ligand complex strongly suggested that the
      molecules active against MabA activity are the oxidized derivative and a major
      cyclic form. Spectrofluorimetry showed that the adduct binds to the MabA active
      site. Modeling of the MabA-adduct complex predicted an interaction between the
      isonicotinoyl moiety of the inhibitor and Tyr185. This hypothesis was supported
      by the fact that a higher 50% inhibitory concentration of the adduct was measured
      for MabA Y185L than for the wild-type enzyme, while both proteins presented
      similar affinities for NADP(+). The crystal structure of MabA Y185L that was
      solved showed that the substitution of Tyr185 induced no significant
      conformational change. The description of the first inhibitor of the beta
      ketoacyl reduction step of fatty acid biosynthesis should help in the design of
      new antituberculous drugs efficient against multidrug-resistant tubercle bacilli.

PMID- 14693547
TI  - Peptide deformylase inhibitors as antibacterial agents: identification of
      VRC3375, a proline-3-alkylsuccinyl hydroxamate derivative, by using an integrated
      combinatorial and medicinal chemistry approach.
AB  - Peptide deformylase (PDF), a metallohydrolase essential for bacterial growth, is
      an attractive target for use in the discovery of novel antibiotics. Focused
      chelator-based chemical libraries were constructed and screened for inhibition of
      enzymatic activity, inhibition of Staphylococcus aureus growth, and cytotoxicity.
      Positive compounds were selected based on the results of all three assays.
      VRC3375 [N-hydroxy-3-R-butyl-3-(2-S-(tert-butoxycarbonyl)-pyrrolidin-1
      ylcarbonyl)propionamide] was identified as having the most favorable properties
      through an integrated combinatorial and medicinal chemistry effort. This compound
      is a potent PDF inhibitor with a K(i) of 0.24 nM against the Escherichia coli
      Ni(2+) enzyme, possesses activity against gram-positive and gram-negative
      bacterial pathogens, and has a low cytotoxicity. Mechanistic experiments
      demonstrate that the compound inhibits bacterial growth through PDF inhibition.
      Pharmacokinetic studies of this drug in mice indicate that VRC3375 is orally
      bioavailable and rapidly distributed among various tissues. VRC3375 has in vivo
      activity against S. aureus in a murine septicemia model, with 50% effective doses
      of 32, 17, and 21 mg/kg of body weight after dosing by intravenous (i.v.),
      subcutaneous (s.c.), and oral (p.o.) administration, respectively. In murine
      single-dose toxicity studies, no adverse effects were observed after dosing with
      more than 400 mg of VRC3375 per kg by i.v., p.o., or s.c. administration. The in
      vivo efficacy and low toxicity of VRC3375 suggest the potential for developing
      this class of compounds to be used in future antibacterial drugs.

PMID- 14693548
TI  - Flucytosine resistance is restricted to a single genetic clade of Candida
      albicans.
AB  - Population studies have revealed that Candida albicans can be separated into five
      major clades, groups I, II, III, SA, and E. Groups SA and E are highly prevalent
      in South Africa and Europe, respectively, while group II is excluded from the
      southwestern portion of the United State. In each geographical locale, several
      clades exist side by side, suggesting little interclade recombination. These
      results suggest clade-specific phenotypes. In the present study we demonstrate
      that resistance to flucytosine (5FC MIC >/= 32 micro g/ml), an antifungal used
      for the treatment of systemic C. albicans infections, is restricted to clade I.
      In addition, while 97% of all strains for which 5FC MICs were >/=0.5 micro g per
      ml were members of group I, only 3% were members of the other groups. 5FC MICs
      were >/=0.5 micro g per ml for 72% of all group I isolates, while 5FC MICs were
      >/=0.5 micro g per ml for only 2% of all non-group I isolates. These results
      demonstrate for the first time the clade specificity of a clinically relevant
      trait (5FC resistance) and suggest that while intraclade recombination may be
      common, interclade recombination is rare.

PMID- 14693549
TI  - The interferon inducer ampligen [poly(I)-poly(C12U)] markedly protects mice
      against coxsackie B3 virus-induced myocarditis.
AB  - Viral replication, as well as an immunopathological component, is assumed to be
      involved in coxsackie B virus-induced myocarditis. We evaluated the efficacy of
      the interferon inducer Ampligen on coxsackie B3 virus-induced myocarditis in
      C3H/HeNHsd mice. The efficacy of Ampligen was compared with that of the
      interferon inducer poly(inosinic acid)-poly(cytidylic acid) [poly(IC)], alpha
      interferon 2b (INTRON A), and pegylated alpha interferon 2b (PEG-INTRON-alpha
      2b). Ampligen at 20 mg/kg of body weight/day was able to reduce the severity of
      virus-induced myocarditis, as assessed by morphometric analysis, by 98% (P = 3.0
      x 10(-8)). When poly(IC) was administered at 15 mg/kg/day, it reduced the
      severity of virus-induced myocarditis by 93% (P = 5.6 x 10(-5)). Alpha interferon
      2b (1 x 10(5) U/day) and pegylated alpha interferon 2b (5 x 10(5) U/day) were
      less effective and reduced the severity of virus-induced myocarditis by 66% (P =
      0.0009) and 78% (P = 0.0002), respectively. The observed efficacies of Ampligen
      and poly(IC) were corroborated by the observation that the drugs also markedly
      reduced the virus titers in the heart, as detected by (i) quantitative real-time
      reverse transcription-PCR and (ii) titration for infectious virus content.
      Whereas the electrocardiograms for untreated mice with myocarditis were severely
      disturbed, the electrocardiographic parameters were normalized in Ampligen- and
      poly(IC)-treated mice. Even when start of treatment with Ampligen was delayed
      until day 2 postinfection, a time at which lesions had already appeared in
      untreated control animals, a marked protective effect on the development of viral
      myocarditis (as assessed at day 6 postinfection) was still noted.

PMID- 14693550
TI  - Vancomycin-resistant Staphylococcus aureus isolate from a patient in
      Pennsylvania.
AB  - A vancomycin-resistant Staphylococcus aureus (VRSA) isolate was obtained from a
      patient in Pennsylvania in September 2002. Species identification was confirmed
      by standard biochemical tests and analysis of 16S ribosomal DNA, gyrA, and gyrB
      sequences; all of the results were consistent with the S. aureus identification.
      The MICs of a variety of antimicrobial agents were determined by broth
      microdilution and macrodilution methods following National Committee for Clinical
      Laboratory Standards (NCCLS) guidelines. The isolate was resistant to vancomycin
      (MIC = 32 micro g/ml), aminoglycosides, beta-lactams, fluoroquinolones,
      macrolides, and tetracycline, but it was susceptible to linezolid, minocycline,
      quinupristin-dalfopristin, rifampin, teicoplanin, and trimethoprim
      sulfamethoxazole. The isolate, which was originally detected by using disk
      diffusion and a vancomycin agar screen plate, was vancomycin susceptible by
      automated susceptibility testing methods. Pulsed-field gel electrophoresis (PFGE)
      of SmaI-digested genomic DNA indicated that the isolate belonged to the USA100
      lineage (also known as the New York/Japan clone), the most common staphylococcal
      PFGE type found in hospitals in the United States. The VRSA isolate contained two
      plasmids of 120 and 4 kb and was positive for mecA and vanA by PCR amplification.
      The vanA sequence was identical to the vanA sequence present in Tn1546. A DNA
      probe for vanA hybridized to the 120-kb plasmid. This is the second VRSA isolate
      reported in the United States.

PMID- 14693551
TI  - Linezolid pharmacokinetics in adult patients with cystic fibrosis.
AB  - The pharmacokinetics of many drugs are altered in patients with cystic fibrosis
      (CF), often necessitating different dosage requirements than those used in non-CF
      patients. The objective of this study was to determine the pharmacokinetics of
      linezolid, an antibiotic with good activity against gram-positive organisms such
      as methicillin-resistant Staphylococcus aureus, in patients with CF so that
      dosage requirements could be established. Twelve adult patients (6 male) ranging
      in age from 22 to 39 years were studied. A single 600-mg dose was administered
      intravenously over 0.5 h, and plasma samples were collected at 0 (predose), 0.5,
      0.75, 1, 2, 4, 8, and 24 h. Linezolid concentrations were determined with a
      validated high-performance liquid chromatography assay. Pharmacokinetic
      parameters were estimated using standard noncompartmental methods. Blood
      chemistry and hematologic indices were determined before and after the study for
      safety purposes. All patients completed the study without encountering any
      adverse reactions. The pharmacokinetic parameters, while variable, with half
      lives varying from 1.76 to 8.36 h, were similar to those previously described in
      other populations. Mean (+/- standard deviation) values for pharmacokinetic
      parameters of interest were as follows: elimination rate constant, 0.21 (0.11) h(
      1); half-life, 4.41 (2.43); volume of distribution at steady state, 0.87 (0.19)
      liters/kg of body weight; and total body clearance, 0.12 (0.06) liters/h/kg. No
      patient would have achieved the pharmacodynamic target of an area under the
      concentration-time curve/MIC ratio of 83 h for pathogens for which the MIC was 4
      micro g/ml. Patients with inadequate clinical responses to linezolid may require
      more frequent dosing.

PMID- 14693553
TI  - Local variants of Staphylococcal cassette chromosome mec in sporadic methicillin
      resistant Staphylococcus aureus and methicillin-resistant coagulase-negative
      Staphylococci: evidence of horizontal gene transfer?
AB  - The mecA gene in Staphylococcus aureus is located on the genetic element
      staphylococcal cassette chromosome (SCC). Different SCCmecs have been classified
      according to their putative recombinase genes (ccrA and ccrB) and overall genetic
      composition. Clinical isolates of coagulase-negative staphylococci (CoNS; n = 39)
      and S. aureus (n = 20) from Norway, India, Italy, Finland, the United States, and
      the United Kingdom were analyzed by pulsed-field gel electrophoresis, which
      showed that most isolates were genetically unrelated. Cluster analyses of 16S
      rRNA gene and pta sequences confirmed the traditional biochemical species
      identification. The mecI, mecR1, mecA, and ccrAB genes were detected by PCRs,
      identifying 19 out of 20 S. aureus and 17 out of 39 CoNS isolates as carriers of
      one of the three published ccrAB pairs. New variants of SCCmec were identified,
      as well as CoNS isolates containing ccrAB genes without the mec locus. ccrAB and
      mec PCRs were verified by hybridization. Sequence alignments of ccrAB genes
      showed a high level of diversity between the ccrAB alleles from different
      isolates, i.e., 94 to 100% and 95 to 100% homology for ccrAB1 and ccrAB2,
      respectively. All of the ccrAB3 genes identified were identical. Genetically
      unique and sporadic methicillin-resistant S. aureus (MRSA) contained local
      variants of ccrAB gene pairs identical to those found in MR-CoNS but different
      from those in MRSA from other regions. Allelic variants of ccrAB in isolates from
      the same geographic region showed sequence conservation independent of species.
      The species-independent sequence conservation found suggests that there is a
      closer genetic relationship between ccrAB2 in Norwegian staphylococci than
      between ccrAB2 sequences in international MRSA and Norwegian MRSA. This might
      indicate that different staphylococcal species acquire these genes locally by
      horizontal gene transfer.

PMID- 14693554
TI  - Denaturing high-performance liquid chromatography detection of ribosomal
      mutations conferring macrolide resistance in gram-positive cocci.
AB  - Mutations in genes coding for L4 (rplD) or L22 (rplV) ribosomal proteins or in
      23S rRNA (rrl gene) are reported as a cause of macrolide resistance in
      streptococci and staphylococci. This study was aimed at evaluating a denaturing
      high-performance liquid chromatography (DHPLC) technique as a rapid mutation
      screening method. Portions of these genes were amplified by PCR from total DNA of
      48 strains of Streptococcus pneumoniae (n = 22), Staphylococcus aureus (n = 16),
      Streptococcus pyogenes (n = 6), Streptococcus oralis (n = 2), and group G
      streptococcus (n = 2). Thirty-seven of these strains were resistant to macrolides
      and harbored one or several mutations in one or two of the target genes, and 11
      were susceptible. PCR products were analyzed by DHPLC. All mutations were
      detected, except a point mutation in a pneumococcal rplD gene. The method
      detected one mutated rrl copy out of six in S. aureus. This automated method is
      promising for screening of mutations involved in macrolide resistance in gram
      positive cocci.

PMID- 14693556
TI  - Pyridines and pyrimidines mediating activity against an efflux-negative strain of
      Candida albicans through putative inhibition of lanosterol demethylase.
AB  - The first step in ergosterol biosynthesis in Saccharomyces cerevisiae consists of
      the condensation of two acetyl coenzyme A (acetyl-CoA) moieties by acetoacetyl
      CoA thiolase, encoded by ERG10. The inhibition of the sterol pathway results in
      feedback activation of ERG10 transcription. A cell-based reporter assay, in which
      increased ERG10 transcription results in elevated specific beta-galactosidase
      activity, was used to find novel inhibitors of ergosterol biosynthesis that could
      serve as chemical starting points for the development of novel antifungal agents.
      A class of pyridines and pyrimidines identified in this way had no detectable
      activity against the major fungal pathogen Candida albicans (MICs > 64 micro g.
      ml(-1)). However, a strain of C. albicans lacking the Cdr1p and Cdr2p efflux
      pumps was sensitive to the compounds (with MICs ranging from 2 to 64 micro g. ml(
      1)), suggesting that they are efficiently removed from wild-type cells.
      Quantitative analysis of sterol intermediates that accumulated during growth
      inhibition revealed the accumulation of lanosterol at the expense of ergosterol.
      Furthermore, a clear correlation was found between the 50% inhibitory
      concentration at which the sterol profile was altered and the antifungal
      activity, measured as the MIC. This finding strongly suggests that the inhibition
      of growth was caused by a reduction in ergosterol synthesis. The compounds
      described here are a novel class of antifungal pyridines and pyrimidines and the
      first pyri(mi)dines to be shown to putatively mediate their antifungal activity
      against C. albicans via lanosterol demethylase.

PMID- 14693555
TI  - Genetic and biochemical characterization of the chromosomal class A beta
      lactamases of Raoultella (formerly Klebsiella) planticola and Raoultella
      ornithinolytica.
AB  - Enterobacterial strains of Raoultella spp. display a penicillinase-related beta
      lactam resistance pattern suggesting the presence of a chromosomal bla gene. From
      whole-cell DNA of Raoultella planticola strain ATCC 33531(T) and Raoultella
      ornithinolytica strain ATCC 31898(T), bla genes were cloned and expressed into
      Escherichia coli. Each gene encoded an Ambler class A beta-lactamase, named PLA-1
      and ORN-1 for R. planticola and R. ornithinolytica, respectively. These beta
      lactamases (291 amino acids), with the same pI value of 7.8, had a shared amino
      acid identity of 94%, 37 to 47% identity with the majority of the chromosome
      encoded class A beta-lactamases previously described for Enterobacteriaceae, and
      66 to 69% identity with the two beta-lactamases LEN-1 and SHV-1 from Klebsiella
      pneumoniae. However, the highest identity percentage (69 to 71%) was found with
      the plasmid-mediated beta-lactamase TEM-1. PLA-1, which displayed very strong
      hydrolytic activity against penicillins, also displayed significant hydrolytic
      activity against cefepime and, to a lesser extent, against cefotaxime and
      aztreonam, but there was no hydrolytic activity against ceftazidime. Such a
      substrate profile suggests that the Raoultella beta-lactamases PLA-1 and ORN-1
      should be classified into the group 2be of the beta-lactamase classification of
      K. Bush, G. A. Jacoby, and A. A. Medeiros (Antimicrob. Agents Chemother. 39:1211
      1233, 1995). The highly homologous regions upstream of the bla(PLA-1A) and
      bla(ORN-1A) genes comprised a nucleotide sequence identical to the -35 region and
      another one very close to the -10 region of the bla(LEN-1) gene. From now on, as
      the bla gene sequences of the most frequent Raoultella and Klebsiella species are
      available, the bla gene amplification method can be used to differentiate these
      species from each other, which the biochemical tests currently carried out in the
      clinical laboratory are unable to do.

PMID- 14693557
TI  - FKS1 mutations responsible for selective resistance of Saccharomyces cerevisiae
      to the novel 1,3-beta-glucan synthase inhibitor arborcandin C.
AB  - Arborcandin C is a novel antibiotic with potent antifungal activity that inhibits
      1,3-beta-glucan synthase in fungi. We examined spontaneous Saccharomyces
      cerevisiae mutants which are selectively resistant to arborcandin C and revealed
      that a single amino acid replacement in Fks1p of Asn(470) with Lys or of Leu(642)
      with Ser confers selective resistance on Fks1p mutants.

PMID- 14693558
TI  - In vitro activities of tigecycline against erythromycin-resistant Streptococcus
      pyogenes and Streptococcus agalactiae: mechanisms of macrolide and tetracycline
      resistance.
AB  - The activity of tigecycline was tested against erythromycin-resistant
      streptococci (107 Streptococcus pyogenes and 98 Streptococcus agalactiae
      strains). The presence of erythromycin and tetracycline resistance genes was
      determined by PCR. Among S. pyogenes strains the most prevalent gene was mef(A)
      (91.6%). The erm(B) gene was the most prevalent (65.3%) among S. agalactiae
      strains. Tigecycline proved to be very active against all the isolates tested
      (MIC at which 90% of the isolates tested were inhibited, 0.06 micro g/ml),
      including those resistant to tetracycline.

PMID- 14693559
TI  - Effect of parenteral fluoroquinolone administration on persistence of vancomycin
      resistant Enterococcus faecium in the mouse gastrointestinal tract.
AB  - We examined the effect of subcutaneous fluoroquinolone antibiotic administration
      on persistence and density of vancomycin-resistant Enterococcus faecium stool
      colonization in mice. Levofloxacin and ciprofloxacin did not promote colonization
      in comparison to saline controls, whereas moxifloxacin and gatifloxacin promoted
      persistent overgrowth in a dose-dependent fashion.

PMID- 14693560
TI  - blaVIM-7, an evolutionarily distinct metallo-beta-lactamase gene in a Pseudomonas
      aeruginosa isolate from the United States.
AB  - As part of the CANCER Antimicrobial Surveillance Program in North America, a
      Pseudomonas aeruginosa isolate, strain 07-406, was shown to possess a metallo
      beta-lactamase, designated VIM-7. bla(VIM-7) is located on a 24-kb plasmid which
      can be readily transferred into Enterobacteriaceae and other pseudomonads. This
      is the first report of a mobile metallo-beta-lactamase gene, bla(VIM-7), being
      detected within the United States.

PMID- 14693561
TI  - Effect of heat-treated amphotericin B on renal and fungal cytotoxicity.
AB  - The purpose of this investigation was to determine the cytotoxicity of
      amphotericin B (AMB; trade name Fungizone [FZ]) following the administration of
      FZ and a heat-treated form of FZ (HFZ) to LLC-PK(1) pig kidney cells and
      Cryptococcus neoformans var. gattii cells. HFZ was significantly less toxic to
      kidney cells than FZ at all concentrations tested. For both FZ and HFZ, the
      concentration range which resulted in a 50% reduction of the growth of fungal
      cells was 0.125 to 1 mg/ml. These findings suggest that heat treatment decreases
      AMB's renal cytotoxicity without modifying its antifungal activity.

PMID- 14693562
TI  - In vitro evaluation of nonnucleoside reverse transcriptase inhibitors UC-781 and
      TMC120-R147681 as human immunodeficiency virus microbicides.
AB  - The nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681
      (Dapivirine) effectively prevented human immunodeficiency virus (HIV) infection
      in cocultures of monocyte-derived dendritic cells and T cells, representing
      primary targets in sexual transmission. Both drugs had a favorable therapeutic
      index. A 24-h treatment with 1,000 nM UC-781 or 100 nM TMC120-R147681 prevented
      cell-free HIV infection, whereas 10-fold-higher concentrations blocked cell
      associated HIV.

PMID- 14693563
TI  - In vitro postantibiotic effects of rifapentine, isoniazid, and moxifloxacin
      against Mycobacterium tuberculosis.
AB  - Postantibiotic effects (PAEs) of rifapentine, isoniazid, and moxifloxacin against
      Mycobacterium tuberculosis ATCC 27294 were studied using a radiometric culture
      system. Rifapentine at 20 mg/liter gave the longest PAE (104 h) among the drugs
      used alone. The combinations of rifapentine plus isoniazid, rifapentine plus
      moxifloxacin, and isoniazid plus moxifloxacin gave PAEs of 136.5, 59.0, and 8.3
      h, respectively.

PMID- 14693564
TI  - Comparison of in vitro activities of ketolides, macrolides, and an azalide
      against the spirochete Borrelia burgdorferi.
AB  - Two ketolides, three macrolides, and one azalide were tested in vitro against 17
      isolates of the B. burgdorferi s.l. complex. As measured in micrograms per
      milliliter, activity was highest for cethromycin (MIC at which 90% of the tested
      isolates were inhibited [MIC(90)], 0.0019 micro g/ml) and telithromycin (MIC(90),
      0.0078 micro g/ml). Electron-microscope analysis and time-kill studies also
      supported enhanced effectiveness of both ketolides.

PMID- 14693565
TI  - Chromosome-encoded ambler class D beta-lactamase of Shewanella oneidensis as a
      progenitor of carbapenem-hydrolyzing oxacillinase.
AB  - A chromosome-encoded beta-lactamase gene from a Shewanella oneidensis reference
      strain was cloned and expressed in Escherichia coli. It encoded a carbapenem
      hydrolyzing Ambler class D beta-lactamase, OXA-54, that shared 92% amino acid
      identity with the plasmid-encoded carbapenem-hydrolyzing oxacillinase OXA-48 from
      Klebsiella pneumoniae. This work suggests that Shewanella spp. may produce the
      progenitor of oxacillinases compromising the efficacy of imipenem in clinically
      relevant gram-negative pathogens.

PMID- 14693566
TI  - In vitro activities of DA-7867, a novel oxazolidinone, against recent clinical
      isolates of aerobic and anaerobic bacteria.
AB  - In vitro activities of DA-7867, a novel oxazolidinone, were compared to those of
      linezolid and commonly used antimicrobials. DA-7867 had the lowest MIC for 90% of
      the aerobic gram-positive bacterial strains tested, </=0.25 micro g/ml, and it
      was more potent than linezolid.

PMID- 14693567
TI  - Sequencing of Neisseria meningitidis penA gene: the key to success in defining
      penicillin G breakpoints.
AB  - Testing of susceptibility to penicillin G by E-test and sequencing of an internal
      fragment of the penA gene were done for 43 meningococcal strains. Those strains
      for which the MIC was >/=0.094 micro g/ml showed mosaic alleles, so 0.094 micro
      g/ml is suggested as the penicillin G intermediate breakpoint when E-test is
      used.

PMID- 14693568
TI  - Are Enterococcus faecalis strains with vat(E) in poultry a reservoir for human
      streptogramin resistance? vat(E) occurrence in human enterococcal bloodstream
      infections in North America (SENTRY Antimicrobial Surveillance Program, 2002).

PMID- 14693569
TI  - Emergence of two Klebsiella pneumoniae isolates harboring plasmid-mediated CTX-M
      15 beta-lactamase in Taiwan.

PMID- 14693570
TI  - Type 1 integrons in epidemiologically unrelated Acinetobacter baumannii isolates
      collected at Spanish hospitals.

PMID- 14693571
TI  - In vitro activities of tigecycline (GAR-936) against multidrug-resistant
      Staphylococcus aureus and Streptococcus pneumoniae.

PMID- 14693572
TI  - Perioperative COX-2 inhibitors: knowledge and challenges.

PMID- 14693573
TI  - The effect of preoperative antiplatelet/anticoagulant prophylaxis on
      postoperative blood loss in cardiac surgery.
AB  - In this study we sought to determine whether preoperative treatment with
      antiplatelet and/or anticoagulant drugs influences postoperative blood loss after
      coronary artery bypass graft surgery. Although prophylactic treatment to prevent
      ischemic events preoperatively is often necessary, the treatment frequently
      continues until there may be a risk of increased bleeding (i.e., within 5-7 days
      before surgery). With patient consent, a preincision blood sample was collected
      prospectively from 93 adult subjects who presented randomly. They consisted of 3
      groups regarding their primary preoperative regimen: 1) no preoperative treatment
      within the week before surgery; 2) platelet adenosine diphosphate (ADP) receptor
      antagonist; 3) ADP receptor antagonist plus IV heparin. Postoperative chest tube
      drainage (24 h) in the group that received ADP antagonist alone was more (P <
      0.05) than either of the other groups: 503 +/- 56; 633 +/- 55; 439 +/- 29 mL
      (mean +/- SEM) for Groups 1, 2, and 3, respectively. Combined treatment with ADP
      antagonist plus heparin infusion appeared to prevent the increased blood loss
      with the ADP antagonist alone. Preincision and postoperative plasma fibrinogen
      concentrations were largest (P < 0.05) in the group that received the combination
      treatment; mean +/- SEM for groups 1, 2, and 3 preincision, 311 +/- 17, 366 +/-
      16, and 423 +/- 18 mg/dL, and postoperatively, 229 +/- 16, 267 +/- 13, and 312 +/
      16 mg/dL. Postoperative fibrinogen showed strong dependence on preoperative
      fibrinogen in all groups (r = 0.576 to 0.825; P = 0.01 to 10(-6)). Prevention of
      the increased blood loss in the ADP receptor antagonist group by the addition of
      a heparin infusion may have been attributable to a conservation of coagulation
      factors, as evidenced by the increased plasma fibrinogen concentrations with
      combined prophylactic treatment. IMPLICATIONS: The objective of this study was to
      determine whether preoperative treatment with antiplatelet and/or anticoagulant
      drugs influences the extent of blood loss in the 24-h period after cardiac
      surgery.

PMID- 14693575
TI  - A-type and B-type natriuretic peptides in cardiac surgical procedures.
AB  - This study was performed to determine the secretion pattern and prognostic value
      of A-type (ANP) and B-type (BNP) natriuretic peptide in patients undergoing
      cardiac surgical procedures. We measured ANP and BNP in patients undergoing
      coronary artery bypass grafting (CABG) with (n = 28) or without (n = 32)
      ventricular dysfunction and in patients undergoing mitral (n = 21) or aortic (n =
      24) valve replacement, respectively. Postoperative mortality was recorded up to
      730 days after operation. ANP, but not BNP, concentrations were closely
      associated with volume reloading of the heart after aortic cross-clamp in all
      patients. The secretion pattern of BNP during surgery was much less uniform. BNP,
      but not ANP, concentrations correlated with aortic cross-clamp time (r(2) = 0.32;
      P = 0.006) and postoperative troponin I concentrations (r(2) = 0.22; P = 0.0009)
      in bypass patients, and preoperative BNP increases were associated with a more
      frequent postoperative (2-yr) mortality in these patients. Markedly increased
      preoperative BNP concentrations in mitral (3-fold) and aortic (14-fold) valve
      disease patients did not further increase during cardiopulmonary surgery. The
      data suggest that ANP is primarily influenced by intravascular volume reloading
      of the heart after cross-clamp, whereas the secretion of BNP is related to other
      factors, such as duration of ischemia and long-term left ventricular pressure
      and/or excessive intravascular volume. BNP, but not ANP, was shown to be a
      mortality risk predictor in patients undergoing CABG. IMPLICATIONS: A-type
      natriuretic peptide is primarily influenced by volume reloading of the heart
      after cross-clamp, whereas the secretion of B-type natriuretic peptide (BNP) is
      related to the duration of ischemia and long-term left ventricular pressure
      and/or volume overload. Preoperative BNP, but not postoperative BNP,
      concentrations predict long-term outcome after coronary artery bypass grafting.

PMID- 14693576
TI  - Myocardial protection using fructose-1,6-diphosphate during coronary artery
      bypass graft surgery: a randomized, placebo-controlled clinical trial.
AB  - In vitro and in vivo studies suggest that fructose-1,6-diphosphate (FDP), an
      intermediary glycolytic pathway metabolite, ameliorates ischemic tissue injury
      through increased high-energy phosphate levels and may therefore have
      cardioprotective properties in patients undergoing coronary artery bypass graft
      (CABG) surgery. We designed a randomized, placebo-controlled, double-blinded,
      sequential-cohort, dose-ranging safety study to test 5 FDP dosage regimens in
      patients (n = 120; 60 FDP, 60 control) undergoing CABG surgery. Of these dosage
      regimens, 3 produced no benefit, 1 produced improved cardiac function, and 1
      required adjustment as a result of metabolic acidosis. This suggests that we
      achieved the intended effect of a dose-ranging study. The expected response was
      observed in patients treated with 250 mg/kg FDP IV before surgery and 2.5 mM FDP
      as a cardioplegic additive (n = 15). These patients had lower serum creatine
      kinase-MB levels 2, 4, and 6 h after reperfusion (P < 0.05), fewer perioperative
      myocardial infarctions (P < 0.05), and improved postoperative cardiac function,
      as evidenced by higher left ventricular stroke work index (LVSWI) 6, 12, and 16 h
      (P < 0.01) and cardiac index (CI) at 12 and 16 h (P < 0.05) after reperfusion.
      Overall efficacy of FDP was tested across all regimens that included IV FDP (n =
      88; 44 FDP, 44 control) using 2 (FDP versus placebo) x 3 (dose size) factorial
      analyses. Area-under-curve (AUC) analysis demonstrated a significant increase in
      CI (AUC-16h, P = 0.013) and LVSWI (AUC-16h, P = 0.003) and reduction in CK-MB
      levels (AUC-16h, P < 0.05) in FDP-treated patients. The internal consistency of
      this dataset suggests that FDP may provide myocardial protection in CABG surgery
      and supports previous laboratory and clinical studies of FDP in ischemic heart
      disease. IMPLICATIONS: Fructose-1,6-diphosphate (FDP) may increase high-energy
      phosphate levels under anaerobic conditions and therefore ameliorate ischemic
      injury. A dose-ranging safety study for FDP was conducted in patients undergoing
      coronary artery surgery. Preischemic provision of FDP significantly improved
      cardiac function and reduced perioperative ischemic injury. These myocardial
      protective effects may improve patient outcome after cardiac surgery.

PMID- 14693578
TI  - The interaction of MCI-154, a calcium sensitizer, and isoflurane on systemic and
      coronary hemodynamics in chronically instrumented dogs.
AB  - We conducted this study to determine the interaction of MCI-154, 6-[4-(4'
      pyridylamino)phenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride, a calcium
      sensitizer, and isoflurane on myocardial contractility as well as systemic and
      coronary hemodynamics in chronically instrumented dogs after pharmacological
      autonomic nervous system activity blockade. MCI-154 increased heart rate and left
      ventricular function with no change in rate pressure product, pressure work
      index, and coronary blood flow, with a decrease in coronary vascular resistance
      (CVR) in the conscious state. Isoflurane decreased heart rate and left
      ventricular function, with a decrease in rate pressure product and pressure work
      index. Isoflurane also decreased CVR, but not coronary blood flow. The
      cardiovascular actions of MCI-154 during isoflurane anesthesia were qualitatively
      similar to those observed in the conscious state. In contrast to the finding in
      the conscious state, MCI-154 reversed the decrease in cardiac output and preload
      recruitable stroke work caused by isoflurane, but these are not significantly
      different from the effects of isoflurane alone. These results indicate that MCI
      154 increases myocardial contractility and decreases CVR without changing
      calculated myocardial oxygen consumption during both the conscious state and
      isoflurane anesthesia. IMPLICATIONS: MCI-154, a calcium sensitizer, restores the
      myocardial contractility depressed by isoflurane and enhances the coronary
      vasodilating effect of isoflurane in chronically instrumented dogs.

PMID- 14693579
TI  - Endoscopic thoracic sympathectomy suppresses baroreflex control of heart rate in
      patients with essential hyperhidrosis.
AB  - Endoscopic thoracic (T2-3 or T3-4) sympathectomy (ETS) is a highly effective
      treatment for palmar hyperhidrosis. Because the T2-3 or T3-4 sympathetic ganglia
      are involved in direct sympathetic innervation of the heart, sympathectomy at
      this level may alter baroreflex control of heart rate. The purpose of our study
      was to examine the influence of ETS on baroreflex responses to pressor and
      depressor stimuli under small-dose sevoflurane anesthesia. We studied 40 patients
      with palmar or axillary hyperhidrosis who were scheduled to receive ETS. In the
      ETS procedure, the sympathetic trunk was identified by using thoracic endoscopy
      and was transected. Before and after ETS, the pressor or depressor test was
      performed by using an IV infusion of phenylephrine or nitroglycerin,
      respectively, under small-dose general anesthesia. Baroreflex sensitivity was
      calculated from R-R intervals and systolic blood pressure. ETS did not change
      heart rate and systemic blood pressure at rest, although ETS significantly
      altered baroreflex in both pressor and depressor tests in all patients.
      Baroreflex was completely suppressed in 1 of 19 patients in the pressor test and
      in 9 of 21 patients in the depressor test. We conclude that baroreflex responses
      are suppressed in patients who receive ETS. IMPLICATIONS: Endoscopic thoracic
      sympathectomy suppressed the baroreflex control of heart rate during pressor and
      depressor tests in patients with palmar or axillary hyperhidrosis.

PMID- 14693580
TI  - Orthostatic hypotension occurs frequently in the first hour after anesthesia.
AB  - Symptoms of orthostatic intolerance are common after general anesthesia and are
      associated with an increased risk of postoperative morbidity. The contribution of
      orthostatic hypotension (OH) has not been well defined. We conducted a head-up
      tilt test on patients after general anesthesia for minor surgery to assess the
      incidence of and risk factors for OH after general anesthesia. One-hundred-four
      patients were enrolled and were prospectively divided into four groups: older
      female, older male, young female, and young male. The incidence of OH was 76.0%,
      72.0%, 45.5%, and 62.5% respectively and was associated with increasing age (P <
      0.05) and posttest dizziness (P < 0.05). Body mass index, preoperative blood
      pressure, ASA class, anesthetic duration, IV fluid administration, and use of
      analgesics and antiemetics in the postanesthetic care unit were not different in
      subjects who demonstrated OH compared with those with a normotensive response.
      Subjects with OH after general anesthesia did not increase their heart rate and
      diastolic blood pressure with a head-up tilt which may have been caused by
      persistent effects of anesthetics on reflex cardiovascular control and/or bedrest
      induced dysregulation of reflex cardiovascular control. We conclude that OH is
      common after general anesthesia for minor surgery and may be the major cause of
      postoperative orthostatic intolerance. IMPLICATIONS: Orthostatic hypotension, a
      failure to maintain blood pressure on assuming an upright posture, is common
      after general anesthesia for minor surgery and may be the major cause of
      postoperative orthostatic intolerance.

PMID- 14693581
TI  - Pituitary apoplexy presenting as unilateral third cranial nerve palsy after
      coronary artery bypass surgery.
AB  - The new onset of pituitary apoplexy is a rare perioperative complication of
      coronary artery bypass surgery. A variety of clinical presentations of pituitary
      apoplexy have been reported including absence of clinical symptoms or headache,
      sudden deterioration of mental status, visual changes, Addisonian crisis, and
      ophthalmoplegia, including third cranial nerve palsy and/or ptosis. Early
      diagnosis and treatment usually results in excellent outcome. We report a case of
      pituitary apoplexy that presented with only a unilateral dilated pupil, ptosis,
      and vision change within 3 h after coronary artery bypass surgery. The patient
      recovered fully after early pituitary tumor resection and hormonal therapy.
      IMPLICATIONS: Unilateral pupil dilation is a rare perioperative complication
      after coronary artery bypass surgery. We report a case of pituitary apoplexy that
      presented clinically as unilateral dilated pupil, ptosis, and visual loss shortly
      after coronary artery bypass surgery.

PMID- 14693582
TI  - Changes in respiratory mechanics among infants undergoing heart surgery.
AB  - Children with excessive pulmonary blood flow (PBF) from congenital heart disease
      have abnormal respiratory mechanics. Exposure to hypothermic cardiopulmonary
      bypass (CPB) adversely affects lung function. We designed this study of 106
      patients to determine the changes in respiratory mechanics in infants younger
      than 1 yr undergoing heart surgery. Dynamic respiratory compliance (Cdyn) and
      total respiratory resistance (Rrs) were measured before surgical incision, after
      sternal closure in the operating room, and after arrival in the intensive care
      unit. The following data were recorded: age, weight, preoperative pulmonary
      infiltrates, preoperative mechanical ventilation, evidence of increased PBF
      before surgery, duration of CPB, duration of aortic cross-clamp, duration of deep
      hypothermic circulatory arrest, use of steroids, and volume of ultrafiltrate
      removed. Repeated-measures analysis of variance with covariate analysis was used
      to determine the effect of each covariate on Cdyn and Rrs at the three time
      periods. Rrs improved after cardiac surgery correcting increases in PBF, and this
      was most pronounced in neonates. Among infants with normal or reduced PBF,
      cardiac surgery with CPB led to a reduction in Cdyn. We consider that the
      benefits of surgical correction of pulmonary overcirculation outweigh the
      negative effects of CPB on respiratory mechanics. IMPLICATIONS: The benefits of
      surgical correction of pulmonary overcirculation outweigh the negative effects of
      cardiopulmonary bypass on respiratory mechanics in infants.

PMID- 14693584
TI  - Clonidine prolongs spinal anesthesia in newborns: a prospective dose-ranging
      study.
AB  - Spinal anesthesia may reduce the incidence of morbidity that follows general
      anesthesia in neonates and in former preterm infants. However, bupivacaine alone
      provides a block too short for complete surgery in up to 40% of the patients.
      Clonidine lengthens spinal anesthesia in adults and caudal block in children
      without significant side effects. We conducted a controlled, prospective, dose
      ranging study of clonidine in spinal anesthesia in 75 neonates, including 50% of
      former preterm infants, undergoing elective inguinal herniorrhaphy. Patients were
      given a spinal anesthetic with either 0.5% plain isobaric bupivacaine (1 mg/kg),
      or bupivacaine plus 0.25, 0.5, 1, or 2 micro g/kg clonidine. Mean arterial blood
      pressure, heart rate, SpO(2), sensory block extension and duration were the main
      data recorded. Mean arterial blood pressure, heart rate, SpO(2), and block
      extension were similar in the five groups. Duration of spinal block increased
      from 67 (58-82) min in the control group up to 111 (93-125) min in the group
      receiving 1 micro g/kg clonidine (P < 0.003). Transient hypotension occurred more
      often (P < 0.05), and caffeine was given more often, when 2 micro g/kg clonidine
      was given. We conclude that 1 micro g/kg clonidine provides a significant
      improvement in spinal anesthesia duration in newborns without significant side
      effects. IMPLICATIONS: Spinal anesthesia is suitable but often too short for
      complete surgery in newborns. This controlled, randomized, prospective, dose
      ranging study was conducted in 75 neonates to test the hypothesis that clonidine
      could significantly lengthen bupivacaine spinal block. Clonidine 1 micro g/kg,
      added to spinal isobaric bupivacaine, doubles the duration of the block without
      significant deleterious hemodynamic or respiratory side effects.

PMID- 14693585
TI  - Single-dose dexmedetomidine reduces agitation after sevoflurane anesthesia in
      children.
AB  - Emergence agitation is a common side effect of sevoflurane anesthesia in
      children. Dexmedetomidine, because of its sedative and analgesic properties,
      might be useful for the management of this adverse effect. We studied the effect
      of dexmedetomidine on recovery characteristics in 90 children aged 1 to 10 yr
      scheduled to undergo superficial lower abdominal and genital surgery. After
      inhaled induction with sevoflurane, patients were randomly assigned to receive
      saline (Group 1, n = 30), dexmedetomidine 0.15 micro g/kg (Group 2, n = 30), or
      dexmedetomidine 0.30 micro g/kg (Group 3, n = 30). After a laryngeal mask airway
      insertion a caudal block was performed in all patients. Maintenance of anesthesia
      was with 1% end-tidal sevoflurane and 50% nitrous oxide and spontaneous
      ventilation. Intraoperative hemodynamic and respiratory variables were recorded
      every 5 min. At the end of anesthesia time to eyes opening (TEO) and
      characteristics of emergence were recorded. General and intraoperative variables
      were similar in the 3 groups. The TEO was 7.5 +/- 5.0 min in Group 1, 8.2 +/- 5.0
      min in Group 2, and 9.8 +/- 4.0 min in Group 3 (NS). The incidence (95%
      confidence interval) of agitation was 37% (20%-54%) in Group 1, 17% (4%-30%) in
      Group 2, and 10% (0%-21%) in Group 3 (P < 0.05). Paired comparisons showed a
      significant difference for Group 1 versus Group 3 (P < 0.05, 95% confidence
      interval of the difference: 7%-47%). The time to discharge from the
      postanesthesia care unit was similar for the 3 groups. We conclude that a dose of
      dexmedetomidine 0.3 micro g/kg administered after induction of anesthesia reduces
      the postsevoflurane agitation in children and with no adverse effects.
      IMPLICATIONS: In children undergoing surgery using sevoflurane anesthesia,
      dexmedetomidine 0.3 micro g/kg administered in 10 min after induction reduced the
      incidence of emergence agitation from 37% in the control group to 10%. No adverse
      effects attributable to dexmedetomidine were observed.

PMID- 14693586
TI  - Levobupivacaine for pediatric spinal anesthesia.
AB  - In this clinical trial we evaluated the clinical effects of levobupivacaine in
      spinal anesthesia in children. An open, noncomparative study was performed on 40
      children, aged 1-14 yr, undergoing elective lower abdominal or lower limb
      surgery. A plain solution of S(-)-bupivacaine 5 mg/mL at a mean dose of 0.3 mg/kg
      body weight (range, 0.2-0.5 mg/kg body weight) was administered via the L3-4 or
      L4-5 interspace with the patient in the lateral decubitus position. After
      injection, the patients were placed supine. The spread and duration of sensory
      analgesia and the degree of motor block were recorded. Satisfactory surgical
      anesthesia was achieved in 39 of the 40 children. One child received supplemental
      anesthesia. The mean highest level of sensory block was T4 (range, T2 to L1), and
      the mean time to the regression of sensory block to T10 was 90 min (range, 43-185
      min). A complete motor block was achieved in 36 children. These results are
      similar to those obtained with racemic bupivacaine in subarachnoid anesthesia in
      children. IMPLICATIONS: This noncomparative, descriptive study showed that
      levobupivacaine, the S(-)-enantiomer of bupivacaine, has equivalent clinical
      efficacy in spinal anesthesia in children to that of racemic bupivacaine.

PMID- 14693588
TI  - Pyloromyotomy in a patient with paramyotonia congenita.
AB  - A 2-mo-old infant with paramyotonia congenita was scheduled for pyloromyotomy and
      repair of inguinal hernia. Diagnosis of paramyotonia congenita was done with
      positive family history, myotonia at eyelids, provocation by cold, and
      electromyogram analysis. Anesthesia was induced via face mask with sevoflurane at
      4 minimum alveolar anesthetic concentration in oxygen. Tracheal intubation was
      attempted without a neuromuscular relaxant. Anesthesia was maintained with
      sevoflurane at 0.5 minimum alveolar anesthetic concentration in oxygen and
      remifentanil infusion at a rate of 0.2 micro g. kg(-1). min(-1). After
      discontinuation of sevoflurane and remifentanil, the patient was awake and had
      full recovery of muscle activity. IMPLICATIONS: The literature concerning general
      anesthesia in paramyotonic patients is limited. We report a case of paramyotonia
      congenita in a 2-mo-old male infant undergoing surgery for pyloric stenosis and
      inguinal hernia after an uneventful anesthesia.

PMID- 14693589
TI  - Spinal chloroprocaine solutions: density at 37 degrees C and pH titration.
AB  - The density and pH of a local anesthetic are important characteristics in its use
      as an intrathecal drug. Preservative- and antioxidant-free formulations of
      chloroprocaine are available and are being investigated for short-duration spinal
      anesthesia. In this study, we evaluated the pH and density (to 5 significant
      digits in g/mL, at 37.0 degrees C) of these new chloroprocaine formulations. In
      addition to plain 2% and 3% chloroprocaine and 2% lidocaine, mixed solutions of
      2% chloroprocaine with epinephrine or with bicarbonate were evaluated. Density
      was also measured after water dilution and after increasing amounts of added
      dextrose. Chloroprocaine, 2% or 3%, is hyperbaric relative to cerebrospinal fluid
      (CSF) before any addition of dextrose (density 1.00123 g/mL and 1.00257 g/mL,
      respectively). When diluted with water, all the solutions are hypobaric relative
      to CSF (density <1.00028 g/mL). Plain 2% lidocaine is the only dextrose-free
      solution measured to be hypobaric (density 1.00004 g/mL). Bisulfite-free 2
      chloroprocaine remains very acidic (pH <4.0), but the pH can be increased to more
      than 7.0 with a small amount of bicarbonate (0.25-0.33 mL/10 mL). The increased
      density of plain chloroprocaine makes it a useful hyperbaric spinal drug without
      the addition of dextrose. IMPLICATIONS: Dextrose-free 2-chloroprocaine is
      hyperbaric relative to cerebrospinal fluid at 37 degrees C, and therefore can be
      used for spinal anesthesia without dextrose. Bisulfite-free 2-chloroprocaine
      remains very acidic (pH <4.0). The pH can be increased to more than 7.0 with a
      small amount of bicarbonate (0.25-0.33 mL/10 mL).

PMID- 14693590
TI  - Spinal 2-chloroprocaine: a comparison with lidocaine in volunteers.
AB  - Subarachnoid lidocaine has been the anesthetic of choice for outpatient spinal
      anesthesia. However, its use is associated with transient neurologic symptoms
      (TNS). Preservative-free formulations of 2-chloroprocaine are now available and
      may compare favorably with lidocaine for spinal anesthesia. In this double
      blinded, randomized, crossover study, we compared spinal chloroprocaine and
      lidocaine in 8 volunteers, each receiving 2 spinal anesthetics: 1 with 40 mg 2%
      lidocaine and the other with 40 mg 2% preservative-free 2-chloroprocaine.
      Pinprick anesthesia, tolerance to transcutaneous electrical stimulation and thigh
      tourniquet, motor strength, and a simulated discharge pathway were assessed.
      Chloroprocaine produced anesthetic efficacy similar to lidocaine, including peak
      block height (T8 [T5-11] versus T8 [T6-12], P = 0.8183) and tourniquet tolerance
      (46 +/- 6 min versus 38 +/- 24 min, P = 0.4897). Chloroprocaine anesthesia
      resulted in faster resolution of sensory (103 +/- 13 min versus 126 +/- 16 min, P
      = 0.0045) and more rapid attainment of simulated discharge criteria (104 +/- 12
      min versus 134 +/- 14 min, P = 0.0007). Lidocaine was associated with mild to
      moderate TNS in 7 of 8 subjects; no subject complained of TNS with chloroprocaine
      (P = 0.0004). We conclude that the anesthetic profile of chloroprocaine compares
      favorably with lidocaine. Reliable sensory and motor blockade with predictable
      duration and minimal side effects make chloroprocaine an attractive choice for
      outpatient spinal anesthesia. IMPLICATIONS: The spinal anesthetic profile of
      chloroprocaine (40 mg) compares favorably with the same dose of spinal lidocaine.
      Reliable sensory and motor blockade with predictable duration and minimal side
      effects and without signs of transient neurological symptoms make chloroprocaine
      an attractive choice for outpatient spinal anesthesia.

PMID- 14693591
TI  - Spinal 2-chloroprocaine: a dose-ranging study and the effect of added
      epinephrine.
AB  - With the availability of preservative- and antioxidant-free 2-chloroprocaine (2
      CP), there may be an acceptable short-acting alternative to lidocaine for spinal
      anesthesia. We examined the safety, dose-response characteristics, and effects of
      epinephrine with spinal 2-CP. Six volunteers per group were randomized to receive
      30, 45, or 60 mg of spinal 2-CP with and without epinephrine. Intensity and
      duration of sensory and motor blockade were assessed. When 11 of the 18
      volunteers complained of vague, nonspecific flu-like symptoms, breaking of the
      blind revealed that all spinal anesthetics associated with the flu-like symptoms
      contained epinephrine. There were no complaints of flu-like symptoms in the
      volunteers who received 2-CP without epinephrine. No further spinal anesthetics
      containing epinephrine were administered, resulting in 29 anesthetics (11 with
      epinephrine, 18 without epinephrine.) Plain 2-CP demonstrated a dose-dependent
      increase in peak block height and duration of effect at all variables except time
      to 2-segment regression and time to regression to T10. Time to complete sensory
      regression with plain 2-CP was 98 +/- 20, 116 +/- 15, and 132 +/- 23 min,
      respectively. 2-CP with epinephrine produced times to complete sensory regression
      of 153 +/- 25, 162 +/- 33, and 148 +/- 29 min, respectively. Preservative and
      antioxidant free 2-CP can be used effectively for spinal anesthesia in doses of
      30-60 mg. Epinephrine is not recommended as an adjunct because of the frequent
      incidence of side effects. IMPLICATIONS: Hyperbaric spinal 2-chloroprocaine is
      effective and has an anesthetic profile appropriate for use in the surgical
      outpatient over the dose range of 30-60 mg without signs of transient neurologic
      symptoms. The addition of epinephrine is not recommended because of the frequent
      incidence of side effects.

PMID- 14693593
TI  - Spinal 2-chloroprocaine: the effect of added fentanyl.
AB  - Chloroprocaine is being investigated as a possible replacement for spinal
      lidocaine. Adding fentanyl to lidocaine increases the quality of spinal
      anesthesia without prolongation of block. We report the characteristics of 2
      chloroprocaine (2-CP) spinal anesthesia with or without fentanyl in 8 volunteers
      receiving 40 mg 2-CP with saline or 20 micro g fentanyl in a double-blinded,
      randomized, crossover manner. Spinal anesthesia was successful for all subjects
      with complete block regression, ambulation, and void by 110 min. Itching occurred
      in all subjects receiving fentanyl, though medication was not required. No
      subject reported signs of transient neurological symptoms. Peak block with
      fentanyl averaged T5 (T3-7) and without fentanyl T9 (L1-T4) (P = 0.005).
      Regression to L1 was 78 +/- 7 min with fentanyl and 53 +/- 19 min without
      fentanyl (P = 0.02). Tourniquet was tolerated for 51 +/- 8 min with fentanyl and
      for 34 +/- 14 min without fentanyl (P = 0.02). Complete regression of block
      occurred at 104 +/- 7 min with fentanyl and by 95 +/- 9 min without fentanyl (P =
      0.02). We conclude that 2-CP spinal anesthesia provides rapid onset and adequate
      potency, giving it a positive profile for ambulatory surgery. The addition of
      fentanyl lengthens regression to L1 and tourniquet tolerance while minimally
      lengthening block duration. IMPLICATIONS: Spinal 2-chloroprocaine (40 mg)
      provides rapid onset and reliable blockade without signs of transient
      neurological symptoms, giving it a positive profile for ambulatory surgical
      settings. The addition of fentanyl appears to lengthen the regression to L1
      dermatome and tourniquet time while minimally lengthening duration of block.

PMID- 14693594
TI  - Spinal 2-chloroprocaine: the effect of added dextrose.
AB  - Spinal 2-chloroprocaine is being investigated as an alternative short-acting
      spinal anesthetic to replace lidocaine for outpatient surgery. Adding dextrose
      increases the baricity of solutions and alters the characteristics of spinal
      anesthesia. In this study, we compared 2-chloroprocaine spinal anesthesia
      performed with or without the addition of dextrose (1.1%). Eight volunteers
      underwent 2 spinal anesthetics, receiving 40 mg 2-chloroprocaine (2 mL, 2%) with
      0.25 mL saline with one and 0.25 mL 10% dextrose with the other in a double
      blinded, randomized, balanced crossover manner. Pinprick anesthesia, tolerance to
      transcutaneous electrical stimulation, and tourniquet, motor strength
      measurements, and time to ambulation and void were assessed. Postvoid residual
      bladder volume was measured via ultrasound. Spinal anesthesia was successful in
      all subjects and regressed within 110 (80-110) min. There was no significant
      difference in peak height T4 (T7-C6), time to achieve peak block height (14 +/- 6
      min), time for 2-segment regression (44 +/- 9 min), regression to L1 (66 +/- 12
      min), tolerance of tourniquet (43 +/- 9 min), or return of motor function (81 +/-
      14 min). Mean postvoid residual volume was larger with dextrose (74 +/- 67 mL
      versus 16 +/- 35 mL; P = 0.02). No subject reported signs of transient neurologic
      symptoms (TNS). In conclusion, spinal 2-chloroprocaine provides adequate potency
      with reliable regression, seemingly without TNS. Adding dextrose does not
      significantly alter spinal block characteristics but increases residual bladder
      dysfunction. Therefore, the addition of glucose to 2-chloroprocaine for spinal
      anesthesia is not necessary. IMPLICATIONS: Spinal chloroprocaine provides
      adequate potency with reliable regression, seemingly without concerns of
      transient neurologic symptoms, and hence an appealing profile for outpatient
      surgery. The addition of dextrose does not alter peak block height or tolerance
      of thigh tourniquet, and increases the degree of residual bladder dysfunction.

PMID- 14693596
TI  - Antagonism of cisatracurium and rocuronium block at a tactile train-of-four count
      of 2: should quantitative assessment of neuromuscular function be mandatory?
AB  - With a train-of-four (TOF) ratio >0.70 as the standard of acceptable recovery,
      postoperative residual paralysis is a frequent occurrence in postanesthesia care
      units (PACUs). However, detailed information regarding prior anesthetic
      management is rarely provided. We examined the incidence of postoperative
      weakness after the administration of cisatracurium and rocuronium when using a
      rigid protocol for muscle relaxant and subsequent neostigmine administration.
      Under desflurane, N(2)O, and opioid anesthesia, tracheal intubation was
      accomplished after either cisatracurium 0.15 mg/kg or rocuronium 0.60 mg/kg. The
      response of the thumb to ulnar nerve stimulation was estimated by palpation.
      Additional increments of muscle relaxant were given as needed to maintain the TOF
      count at 1 or 2. At the conclusion of surgery, at a TOF count of 2, neostigmine
      0.05 mg/kg plus glycopyrrolate 10 micro g/kg was administered. The mechanical TOF
      response was then measured with a force transducer starting 5 min postreversal.
      Patients were observed until a TOF ratio of 0.90 was achieved. There were no
      significant differences in the recovery profiles of cisatracurium versus
      rocuronium. TOF ratios at 10 min postreversal were 0.72 +/- 0.10 and 0.76 +/-
      0.11, respectively. At 15 min postreversal, only one subject in each group had a
      TOF ratio of <0.70. No patient in either group arrived in the PACU with a TOF
      ratio <0.70. Our results suggest that if cisatracurium or rocuronium is
      administered by using the TOF count as a guide, critical episodes of
      postoperative weakness in the PACU should be an infrequent occurrence.
      IMPLICATIONS: After the administration of cisatracurium or rocuronium, train-of
      four (TOF) ratios <0.70 should rarely be observed in the postanesthesia care unit
      if neostigmine-assisted antagonism of residual block is delayed until the tactile
      TOF count at the thumb is 2 or more.

PMID- 14693597
TI  - Pharmacodynamic interactions between cisatracurium and rocuronium.
AB  - The onset and duration of maintenance doses of neuromuscular blocking drugs may
      be influenced by the original neuromuscular blocking drug used. We assessed the
      effect of the interaction between steroidal and benzo-isoquinolinium compounds on
      the clinical duration of maintenance doses of cisatracurium. Sixty adult patients
      undergoing anesthesia with isoflurane, nitrous oxide, and oxygen were randomized
      to receive the following: Group I = rocuronium 0.6 mg/kg followed by
      cisatracurium 0.03 mg/kg when the first twitch in the train-of-four (TOF)
      recovered to 25%, Group II = cisatracurium 0.15 mg/kg followed by cisatracurium
      0.03 mg/kg, and Group III = rocuronium 0.6 mg/kg followed by rocuronium 0.15
      mg/kg. Neuromuscular blockade was monitored using acceleromyography (TOF-Guard,
      Boxtel, The Netherlands). The clinical duration (mean +/- SD) of the first 2
      maintenance doses was 41 +/- 10, 31 +/- 7++, and 25 +/- 8++ min, and 39 +/- 11,
      30 +/- 6+, 29 +/- 9* min in Groups I-III, respectively (*P < 0.05, +P < 0.01, ++P
      < 0.001; Group I versus II and III). Thus, the clinical duration of the first two
      maintenance doses of cisatracurium was prolonged when administered after
      rocuronium. IMPLICATIONS: We assessed the clinical effect of administering
      cisatracurium after an intubating dose of rocuronium in 60 patients undergoing
      isoflurane/nitrous oxide and oxygen anesthesia. The clinical duration of the
      first two maintenance doses of cisatracurium administered after rocuronium was
      significantly prolonged. This supports the contention that combinations of
      structurally dissimilar neuromuscular blocking drugs result in a synergistic
      effect.

PMID- 14693598
TI  - Chronic treatment with antipsychotics enhances intraoperative core hypothermia.
AB  - Antipsychotics can induce hypothermia, but intraoperative temperature regulation
      in schizophrenic patients taking antipsychotics remains unclear. We investigated
      intraoperative temperature regulation and postoperative shivering in chronic
      schizophrenic patients receiving antipsychotics. We studied 30 schizophrenic
      patients and 30 control patients who underwent orthopedic surgery. Tympanic
      membrane temperatures (35.7 degrees C +/- 0.5 degrees C, 35.6 degrees C +/- 0.5
      degrees C, 35.6 degrees C +/- 0.4 degrees C, 35.5 degrees C +/- 0.4 degrees C,
      35.4 degrees C +/- 0.5 degrees C, and 35.4 degrees C +/- 0.3 degrees C) 15, 30,
      45, 60, 75, and 90 min, respectively, after induction in schizophrenic patients
      were significantly (P < 0.001) lower than those (36.5 degrees C +/- 0.5 degrees
      C, 36.4 degrees C +/- 0.5 degrees C, 36.3 degrees C +/- 0.4 degrees C, 36.2
      degrees C +/- 0.5 degrees C, 36.2 degrees C +/- 0.4 degrees C, and 36.1 degrees C
      +/- 0.4 degrees C) in control patients. Mean skin temperatures (31.1 degrees C +/
      0.4 degrees C [P = 0.008], 31.1 degrees C +/- 0.3 degrees C [P = 0.007], and
      31.1 degrees C +/- 0.2 degrees C [P = 0.006]) 60, 75, and 90 min, respectively,
      after induction in schizophrenic patients were significantly lower than those
      (31.5 degrees C +/- 0.3 degrees C, 31.5 degrees C +/- 0.3 degrees C, and 31.5
      degrees C +/- 0.3 degrees C) in control patients. Four of 30 schizophrenic
      patients and 7 of 30 control patients developed postanesthesia shivering. There
      were no significant differences within 1 h after tracheal extubation in tympanic
      membrane temperatures between patients who shivered and those who did not shiver.
      In conclusion, chronic schizophrenic patients were more hypothermic during
      anesthesia. The incidence of postanesthesia shivering was not significantly
      increased. IMPLICATIONS: Antipsychotics inhibit autonomic thermoregulation. This
      is caused by decreased heat production, increased heat loss, and impaired central
      action at the hypothalamus. Thus, schizophrenic patients receiving antipsychotics
      may have impaired intraoperative temperature regulation.

PMID- 14693600
TI  - Are peripheral opioid antagonists the solution to opioid side effects?
AB  - Opioid medication is the mainstay of therapy for severe acute and chronic pain.
      Unfortunately, the side effects of these medications can affect patient comfort
      and safety, thus limiting their proven therapeutic potential. Whereas the main
      analgesic effects of opioids are centrally mediated, many of the common side
      effects are mediated via peripheral receptors. Novel peripheral opioid
      antagonists have been recently introduced that can block the peripheral actions
      of opioids without affecting centrally mediated analgesia. We review the clinical
      and experimental evidence of their efficacy in ameliorating opioid side effects
      and consider what further information might be useful in defining their role.
      IMPLICATIONS: The major analgesic effects of opioid medication are mediated
      within the brain and spinal cord. Many of the side effects of opioids are caused
      by activation of receptors outside these areas. Recently developed peripherally
      restricted opioid antagonists have the ability to block many opioid side effects
      without affecting analgesia.

PMID- 14693602
TI  - Alaris AEP monitor's "Click Detection" does not help to detect inadvertent
      disconnection of headphones during anesthesia.
AB  - Auditory evoked potentials (AEP) can be suppressed by anesthetics dose
      dependently, but may fail to be registered because of the absence of adequate
      auditory stimuli. The Alaris AEP monitor includes the "Click Detection" (CD)
      (generating the message "NO AEP" or "LOW AEP") to detect the loss of auditory
      stimuli. We investigated the accuracy of the CD in 17 patients awake (AWAKE) and
      during anesthesia (ANESTHESIA) with accurately placed headphones (HP) and after
      disconnected HP (No HP) over 5 min each, respectively. Alaris AEP ARX index, CD,
      and Bispectral Index were recorded each minute. Changes were evaluated with the
      Friedman and Wilcoxon test. Sensitivity (SEN) and specificity (SPE) and receiver
      operating characteristic curve were analyzed for the accuracy of the CD. During
      AWAKE after disconnection of the HP, Alaris AEP ARX index decreased significantly
      (P < 0.05). The CD was able to detect No HP after 2 min with a SEN of 88% and a
      SPE of 97%. During ANESTHESIA, no changes were found after HP disconnection. CD
      detected No HP with a SEN of 100% and a SPE of 20%. The CD of the Alaris AEP
      monitor is not able to detect unnoticed disconnection of HP during ANESTHESIA.
      IMPLICATIONS: Signal transmission of auditory evoked potentials can be suppressed
      by anesthetics, but also by disconnection of headphones. In the present study, we
      demonstrate that even the Alaris AEP monitor with the very new feature "Click
      Detection" was not able to detect the loss of headphones during general
      anesthesia with propofol and remifentanil.

PMID- 14693603
TI  - Assessing propofol induction of anesthesia dose using bispectral index analysis.
AB  - In this study we sought to determine the propofol requirement and hemodynamic
      effects as guided by bispectral index (BIS) analysis during induction of
      anesthesia. Sixty patients were enrolled in this study. Propofol, 2 mg/kg, was
      given to Group I for induction. Propofol was administered for induction until
      loss of response to verbal commands and until BIS values were around 50 to Groups
      II and III. After induction, the smallest BIS value was different in Group I.
      Decreases in total propofol dose were 36% and 43% in Groups II and III
      respectively as compared with Group I. The dose of propofol assessed by BIS
      analysis results in an important reduction of propofol requirement without side
      effects. IMPLICATIONS: Hypotension during induction of anesthesia with propofol
      is common. This study has shown that propofol requirement assessed by bispectral
      index analysis during anesthesia induction may decrease the dose and side effects
      and provide for satisfactory depth of anesthesia.

PMID- 14693605
TI  - Correlation of bispectral index and Guedel's stages of ether anesthesia.
AB  - Bispectral index (BIS) analysis is a method of electroencephalograph (EEG)
      analysis based on the interfrequency phase relationships of the EEG, designed to
      quantify anesthetic hypnosis. The BIS was created after concurrent collection of
      EEG and clinical data from a large number of patients anesthetized with various
      drugs over a prolonged period and then performing a Fourier analysis followed by
      a bispectral calculation. The clinical stages of anesthetic depth are very well
      demonstrated in etherized patients. In this study, we studied the BIS changes
      during various stages of ether anesthesia and quantified the hypnotic depth
      during the surgical stage of ether anesthesia. The values for BIS under various
      stages and planes of ether anesthesia were recorded in 21 patients listed for
      short surgical procedures. During diethyl ether anesthesia, BIS initially
      increased and subsequently decreased. During surgical anesthesia, a BIS value of
      30 was observed. IMPLICATIONS: For the first time, bispectral index (BIS) has
      been studied in patients being anesthetized solely with ether. Ether both causes
      an increase and decrease in BIS during induction and emergence. The index
      observed during the surgical stage of ether anesthesia is probably the correct
      value for the depth of hypnosis because no other volatile anesthetic can produce
      the true anesthetic state when used alone. This value could be taken as the value
      to be attained when balanced anesthesia is being practiced.

PMID- 14693607
TI  - Preoperative rofecoxib oral suspension as an analgesic adjunct after lower
      abdominal surgery: the effects on effort-dependent pain and pulmonary function.
AB  - Rofecoxib is a selective cyclooxygenase-2 inhibitor that reduces pain and
      inflammation without inhibiting platelet function. We examined its effects on
      effort-dependent pain, postoperative morphine requirements, and pulmonary
      function in 48 patients recovering from open abdominal surgery. Spirometric
      measurement of forced expiratory volume(1) and vital capacity (FVC) were assessed
      preoperatively. One hour before the induction of a standardized general
      anesthetic, patients were given either placebo oral suspension (Group A), or
      rofecoxib oral suspension (25 mg [Group B] or 50 mg [Group C]) in a double
      blinded manner. Postoperative pain control was provided with IV morphine in the
      postanesthesia care unit and IV-patient-controlled analgesia morphine on the
      patient care unit. Morphine dose, pain intensity at rest, and pain after
      respiratory effort (postoperative spirometry) were assessed at 12 and 24 h after
      study drug administration. The patient-controlled analgesia morphine dose at 24 h
      was reduced 44% in Group B (30.3 +/- 17.5 mg) and 59% in Group C (22.1 +/- 16.5
      mg) versus Group A (53.7 +/- 31.1 mg); P < 0.01 (A versus B). At 12 h, pain
      scores at rest and after spirometry were lower in Groups B and C than in A (P <
      0.05). At 24 h, resting pain scores were lowest in Group C (P < 0.05). Twelve
      hour FVC was best preserved in Group C (P < 0.03). There were no inter-group
      differences in adverse effects or perioperative blood loss. Rofecoxib oral
      suspension provided a morphine-sparing effect, as well as improvements in pain
      control and 12-h FVC in patients recovering from open abdominal surgery.
      IMPLICATIONS: Rofecoxib belongs to class of analgesics known as cyclooxygenase-2
      inhibitors that reduce pain and inflammation with less risk of bleeding than
      standard nonsteroidal antiinflammatory drugs. We found that patients treated with
      rofecoxib 25 or 50 mg before open abdominal surgery required less IV morphine
      during the first day of recovery. Despite reductions in morphine requirements,
      rofecoxib-treated patients reported lower pain intensity scores at rest and after
      a vigorous cough. In the 50-mg group, improvements in pain control correlated
      with greater preservation of baseline cough effectiveness (vital capacity) at 12
      h. These findings may offer clinical advantages in patients with preexisting
      pulmonary disease.

PMID- 14693608
TI  - Acupuncture decreases somatosensory evoked potential amplitudes to noxious
      stimuli in anesthetized volunteers.
AB  - The effect of acupuncture on pain perception is controversial. Because late
      amplitudes of somatosensory evoked potentials (SEPs) to noxious stimuli are
      thought to correlate with the subjective experience of pain intensity, we
      designed this study to detect changes of these SEPs before and after acupuncture
      in a double-blinded fashion. Sixteen volunteers were anesthetized by propofol and
      exposed to painful electric stimuli to the right forefinger. Then, blinded to the
      research team, the acupuncture group (n = 8) was treated with electric needle
      acupuncture over 15 min at analgesic points of the leg, whereas the sham group (n
      = 8) received no treatment. Thereafter, nociceptive stimulation was repeated.
      SEPs were recorded during each noxious stimulation from the vertex Cz, and
      latencies and amplitudes of the N150 and P260 components were analyzed by
      analysis of variance. P260 amplitudes decreased from 4.40 +/- 2.76 microV (mean
      +/- SD) before treatment to 1.67 +/- 1.21 microV after treatment (P < 0.05),
      whereas amplitudes of the sham group remained unchanged (2.64 +/- 0.94 microV
      before versus 2.54 +/- 1.54 microV after treatment). In conclusion, this double
      blinded study demonstrated that electric needle acupuncture, as compared with
      sham treatment, significantly decreased the magnitudes of late SEP amplitudes
      with electrical noxious stimulation in anesthetized subjects, suggesting a
      specific analgesic effect of acupuncture. IMPLICATIONS: This double-blinded study
      demonstrates that electric needle acupuncture, as compared with sham treatment,
      significantly decreases the magnitudes of late somatosensory evoked potential
      amplitudes with electrical noxious stimulation in anesthetized subjects,
      suggesting a specific analgesic effect of acupuncture.

PMID- 14693610
TI  - Antinociceptive and neurotoxicologic screening of chronic intrathecal
      administration of ketorolac tromethamine in the rat.
AB  - Many drugs are tested intrathecally to investigate alternatives to opioids. We
      aimed to explore the analgesic and possible neurotoxic effects of chronic
      intrathecally-administered ketorolac tromethamine in rats. Catheters were placed
      via atlantoaxial interval in 28 Wistar rats under anesthesia of intraperitoneally
      injected thiopental 30 mg/kg. Rats were randomized into 4 groups and administered
      4 repeated intrathecal doses of therapy with 5-day intervals. The control group
      received 10 microL of saline, and the other groups received 50, 150, and 400
      microg of ketorolac tromethamine respectively. The formalin test, behavioral
      test, and histopathological examination of four different spinal cord levels were
      performed. Neither behavioral testing nor histopathological examination revealed
      abnormalities that would suggest neurotoxicity. Formalin tests showed that both
      phase I and phase II responses of ketorolac tromethamine groups were
      significantly less than those of the control group. Although phase I responses
      did not differ during comparisons among ketorolac tromethamine-administered
      groups, phase II responses decreased significantly in groups that received 150
      and 400 microg of ketorolac tromethamine. Intrathecally administered ketorolac
      tromethamine reduced nociceptive responses and exhibited no untoward neurological
      effect even at large doses. However, its intrathecal use as a safe alternative
      drug for chronic pain remains to be investigated in other species. IMPLICATIONS:
      The present study is unique because it has demonstrated that chronic intrathecal
      administration of ketorolac tromethamine in rats, even at considerably large
      doses, showed a potent analgesic effect during the formalin test without
      exhibiting any neurotoxic side effect.

PMID- 14693611
TI  - The efficacy of dexmedetomidine versus morphine for postoperative analgesia after
      major inpatient surgery.
AB  - Thirty-four patients scheduled for elective inpatient surgery were randomized
      equally to receive either dexmedetomidine (initial loading dose of 1- microg/kg
      over 10 min followed by 0.4 microg. kg(-1). h(-1) for 4 h) or morphine sulfate
      (0.08 mg/kg) 30 min before the end of surgery. We determined heart rate (HR),
      mean arterial blood pressure (MAP), respiratory rate (RR), sedation and analgesia
      (visual analog scale), and use of additional morphine in the postanesthesia care
      unit (PACU) and up to 24 h after surgery. Groups were similar for patient
      demographics, ASA physical status, surgical procedure, baseline hemodynamics, and
      intraoperative use of drugs and fluids. Dexmedetomidine-treated patients had
      slower HR in the PACU (by an average of 16 bpm), whereas MAP, RR, and level of
      sedation were similar between groups. During Phase I recovery, dexmedetomidine
      treated patients required significantly less morphine to achieve equivalent
      analgesia (PACU dexmedetomidine group, 4.5 +/- 6.8 mg; morphine group, 9.2 +/-
      5.2 mg). Sixty minutes into recovery only 6 of 17 dexmedetomidine patients
      required morphine in contrast to 15 of 17 in the morphine group. The
      administration of dexmedetomidine before the completion of major inpatient
      surgical procedures significantly reduced, by 66%, the early postoperative need
      for morphine and was associated with a slower HR in the PACU. IMPLICATIONS: The
      use of dexmedetomidine for postoperative analgesia resulted in significantly less
      additional pain medication (morphine) and slower heart rates than a control group
      receiving only morphine. These outcomes may prove advantageous for patients who
      might be placed at higher risk by tachycardia or large doses of morphine.

PMID- 14693612
TI  - Assessing analgesia in single and repeated administrations of propacetamol for
      postoperative pain: comparison with morphine after dental surgery.
AB  - We conducted this double-blinded, randomized study to assess the analgesic effect
      of repeated administrations of paracetamol, administered as propacetamol, an
      injectable prodrug formulation of paracetamol, and to compare this with the
      analgesic effects of morphine. Patients experiencing moderate to severe pain
      after elective surgical removal of bone-impacted third-molar teeth under general
      anesthesia were randomly assigned to receive IV propacetamol 2 g (n = 31), IM
      morphine 10 mg (n = 30), or placebo (n = 34). Five hours later, the treatments
      were readministered at half of the previous dosages. Standard measures of
      analgesia were collected repeatedly for 10 h. Propacetamol and morphine were
      significantly more effective than placebo in all primary measures of analgesia
      over 5 h after the first administration and globally over 10 h (first and second
      administrations). After the first dose, 21 of the 34 patients in the placebo
      group required rescue medication, compared with 6 of the 31 in the propacetamol
      group (P < 0.0009) and 4 of the 30 in the morphine group (P < 0.0001). No
      statistically or clinically significant differences were found between
      propacetamol and morphine for any sum or peak measures of analgesia. No serious
      adverse events were reported; adverse events were significantly less frequent in
      the propacetamol group than in the morphine group (P < 0.027). Propacetamol
      administered IV in repeated doses (2 g followed by 1 g) has a significant
      analgesic effect that is indistinguishable from that of morphine administered IM
      (10 mg followed by 5 mg) after dental surgery, with better tolerability.
      IMPLICATIONS: After moderately painful surgical procedures, IV paracetamol,
      administered as propacetamol, may be an asset in the control of acute
      postoperative pain.

PMID- 14693613
TI  - The pharmacokinetics and efficacy of ropivacaine continuous wound instillation
      after spine fusion surgery.
AB  - Because local anesthetic continuous wound instillation has not been evaluated
      after spine fusion surgery, we designed this study to determine whether this
      technique could enhance analgesia and improve patient outcome after posterior
      lumbar arthrodesis. Thirty-eight patients undergoing spine stabilization were
      randomly divided into two groups. The M group received a postoperative baseline
      IV infusion of morphine plus ketorolac for 24 h, and the R group received IV
      saline. In both groups, a multihole 16-gauge catheter was placed subcutaneously;
      in the R group, the wound was infiltrated with a solution of ropivacaine 0.5% 200
      mg/40 mL, and infusion of ropivacaine 0.2% 5 mL/h was maintained for 55 h. In the
      M group, saline infusion was given at the same rate. Pain scores were taken at
      rest and on passive mobilization by nurses blinded to patient analgesic
      treatment. The total plasma ropivacaine concentration was evaluated. Pain scores
      and rescue medication requirements (diclofenac and tramadol) were significantly
      less in the R group than in the M group. Postoperative blood loss was less and
      the length of hospital stay was shorter in the R group. The ropivacaine peak
      total plasma concentration occurred at 24 h during infusion and was within safe
      limits; no toxic local anesthetic side effects were observed. These results
      suggest that wound infiltration and continuous instillation of ropivacaine 0.2%
      is effective for pain management after spine stabilization surgery. IMPLICATIONS:
      Postoperative pain after lumbar arthrodesis is related to soft tissue and muscle
      dissection and to manipulations and removal at the operation site. By blocking
      noxious stimuli from the surgical area, infiltration and wound perfusion with
      ropivacaine were more effective in controlling pain than systemic analgesia.

PMID- 14693614
TI  - The sunburn pain model: the stability of primary and secondary hyperalgesia over
      10 hours in a crossover setting.
AB  - It was our aim to study the within-day stability and between-day repeatability of
      ultraviolet B (UVB) light-induced primary and secondary hyperalgesia over 10 h.
      Twenty hours after UVB irradiation of a skin spot (r = 2.5 cm) on the upper leg
      of 8 healthy volunteers the areas of secondary hyperalgesia to pinprick and pain
      tolerance thresholds to heat (HPTT) and electrical stimuli (5 and 250 Hz,
      electrical pain tolerance thresholds [EPTT]) were assessed. Measurements were
      repeated for 10 h at 2-h intervals and in 2 different sessions. Large areas of
      secondary hyperalgesia to pin prick were observed (5995 mm(2); SD, 1645). Primary
      hyperalgesia was evidenced by significant decreases of HPTT (mean difference, 6.5
      degrees C; 95% confidence interval, 6.1-6.8; P < 0.001) and EPTT at 250 Hz (mean
      difference, 0.45 mA; 95% confidence interval, 0.13-0.78; P < 0.05) compared to
      normal skin. There was no trend within one session of either primary (P = 0.14
      for HPTT) or secondary hyperalgesia (P = 0.95) and no difference between the two
      sessions (primary hyperalgesia, P = 0.28; secondary hyperalgesia, P = 0.07). The
      sunburn pain model provides a long time course of stable hyperalgesia with a high
      within-day stability and between-day repeatability for primary and secondary
      hyperalgesia. IMPLICATIONS: The sunburn pain model provides a long time course of
      stable hyperalgesia with a high within-day stability and between-day
      repeatability for primary and secondary hyperalgesia.

PMID- 14693615
TI  - Amiodarone decreases heat, cold, and mechanical hyperalgesia in a rat model of
      neuropathic pain.
AB  - Lidocaine is effective in controlling ventricular dysrhythmia and neuropathic
      pain. Amiodarone, like lidocaine, has sodium channel blocking properties. In the
      present study we explore whether amiodarone has a similar effect as lidocaine on
      the heat, cold, and mechanical hyperalgesia seen in the rat model of neuropathic
      pain. Ten male Sprague-Dawley rats were anesthetized. Four loose ligatures were
      placed on the sciatic nerve of the right hindpaw. A sham operation was performed
      on the contralateral hindpaw (control). Heat hyperalgesia was determined by
      comparing each paw withdrawal latency to heat stimulation (radiant heat source,
      50 degrees C). Cold hyperalgesia was assessed with acetone application.
      Mechanical hyperalgesia was determined by comparing the mechanical threshold in
      the ligated and control hind paws using calibrated von Frey filaments. Amiodarone
      was intraperitoneally administered at doses of 1, 5, 10, 20, 50, and 100 mg/kg
      after the development of hyperalgesia. The animals were tested for hyperalgesia
      before and 1, 3, and 24 h after the administration of a single dose of
      amiodarone. Intrathecal catheters were implanted in 5 new rats, and amiodarone 5
      mg/kg was injected. Testing for heat, mechanical, and cold hyperalgesia was
      performed similarly in the intrathecal amiodarone administration group.
      Amiodarone produces statistically significant decreases of heat, cold, and
      mechanical hyperalgesia after intraperitoneal administration. Results are
      statistically significant at 10 mg/kg (heat hyperalgesia), 20 mg/kg (mechanical
      hyperalgesia), and 100 mg/kg (cold hyperalgesia) intraperitoneally. Hyperalgesia
      returns 24 h after a dose. The intrathecal administration of amiodarone produces
      a nonstatistically significant reduction of hyperalgesia. Amiodarone seems to
      have a similar effect as lidocaine on the hyperalgesia seen in the rat model of
      neuropathic pain. As the half-life of amiodarone is significantly longer that
      that of lidocaine (mean, 53 days versus 90 min) in humans, it may have the
      potential to provide a longer lasting (and perhaps more effective) effect than
      lidocaine on neuropathic pain states. IMPLICATIONS: Amiodarone was found to
      produce a statistically significant decrease in heat, cold, and mechanical
      hyperalgesia in a rat model of neuropathic pain after intraperitoneal injection.
      Considering its long half-life in humans, amiodarone has the potential to provide
      long lasting pain relief in neuropathic pain states.

PMID- 14693616
TI  - Reduction in [D-Ala2, NMePhe4, Gly-ol5]enkephalin-induced peripheral
      antinociception in diabetic rats: the role of the L-arginine/nitric oxide/cyclic
      guanosine monophosphate pathway.
AB  - To test our hypothesis that the abnormally small efficacy of mu-opioid agonists
      in diabetic rats may be due to functional changes in the L-arginine/nitric oxide
      (NO)/cyclic guanosine monophosphate (cGMP) pathway, we evaluated the effects of N
      iminoethyl-L-ornithine, methylene blue, and 3-morpholino-sydnonimine on [D
      Ala(2), NMePhe(4), Gly-ol(5)]enkephalin (DAMGO)-induced antinociception in both
      streptozotocin (STZ)-diabetic and nondiabetic rats. Animals were rendered
      diabetic by an injection of STZ (60 mg/kg intraperitoneally). Antinociception was
      evaluated by the formalin test. The mu-opioid receptor agonist DAMGO (1 microg
      per paw) suppressed the agitation response in the second phase. The
      antinociceptive effect of DAMGO in STZ-diabetic rats was significantly less than
      in nondiabetic rats. N-Iminoethyl-L-ornithine (100 microg per paw), an NO
      synthase inhibitor, or methylene blue (500 microg per paw), a guanylyl cyclase
      inhibitor, significantly decreased DAMGO-induced antinociception in both diabetic
      and nondiabetic rats. Furthermore, 3-morpholino-sydnonimine (200 microg per paw),
      an NO donor, enhanced the antinociceptive effect of DAMGO in nondiabetic rats but
      did not change in diabetic rats. These results suggest that the peripheral
      antinociceptive effect of DAMGO may result from activation of the L
      arginine/NO/cGMP pathway and dysfunction of this pathway; also, events that are
      followed by cGMP activation may have contributed to the demonstrated poor
      antinociceptive response of diabetic rats to mu-opioid agonists. IMPLICATIONS:
      This is the first study on the role of the nitric oxide (NO)/cyclic guanosine
      monophosphate pathway on [D-Ala(2), NMePhe(4), Gly-ol(5)]enkephalin (DAMGO)
      induced peripheral antinociception and the effect of diabetes on this pathway.
      The study suggests a possible role of DAMGO as a peripherally-acting analgesic
      drug.

PMID- 14693617
TI  - Postanesthesia care unit recovery times and neuromuscular blocking drugs: a
      prospective study of orthopedic surgical patients randomized to receive
      pancuronium or rocuronium.
AB  - In this study, we examined the effect of choice of neuromuscular blocking drug
      (NMBD) (pancuronium versus rocuronium) on postoperative recovery times and
      associated adverse outcomes in patients undergoing orthopedic surgical
      procedures. Seventy patients were randomly allocated to a pancuronium or
      rocuronium group. On arrival to the postanesthesia care unit (PACU) and again 30
      min later, train-of-four ratios were quantified by using acceleromyography.
      Immediately after acceleromyographic measurements, patients were assessed for
      signs and symptoms of residual paresis. During the PACU admission, episodes of
      hypoxemia, nausea, and vomiting were recorded. The time required for patients to
      meet discharge criteria and the time of actual PACU discharge were noted. Forty
      percent of patients in the pancuronium group had train-of-four ratios <0.7 on
      arrival to the PACU, compared with only 5.9% of subjects in the rocuronium group
      (P < 0.001). Patients in the pancuronium group were more likely to experience
      symptoms of muscle weakness (blurry vision and generalized weakness; P < 0.001)
      and hypoxemia (10 patients in the rocuronium group versus 21 patients in the
      pancuronium group; P = 0.015) during the PACU admission. Significant delays in
      meeting PACU discharge criteria (50 min [45-60 min] versus 30 min [25-40 min])
      and achieving actual discharge (70 min [60-90 min] versus 57.5 min [45-61 min])
      were observed when the pancuronium group was compared with the rocuronium group
      (P < 0.001). In conclusion, our study indicates that PACU recovery times may be
      prolonged when long-acting NMBDs are used in surgical patients. IMPLICATIONS:
      Clinical recovery may be delayed in surgical patients administered long-acting
      neuromuscular blocking drugs. During the postanesthesia care unit admission,
      patients randomized to receive pancuronium (versus rocuronium) were more likely
      to exhibit symptoms of muscle weakness, develop hypoxemia, and require more time
      to meet discharge criteria.

PMID- 14693619
TI  - Economic analysis of an intraoperative cell salvage service.
AB  - In the United States, the cost of erythrocyte transfusion exceeds 1.3 billion
      dollars annually. The fear of viral disease transmission popularized
      intraoperative salvage to reduce the use of banked blood. Although the economics
      of this technique have been questioned, the financial variables in providing an
      intraoperative autotransfusion service have not been analyzed. We designed
      mathematical models to determine the most cost-effective strategy based on
      hospital caseload. Four models were analyzed with a spreadsheet to project costs
      of an intraoperative autotransfusion service when fully or partially outsourced,
      performed by a full-time technician employee, or performed by a cross-trained
      employee. The Partially Outsourced model was more economical than the Fully
      Outsourced model when the annual caseload exceeded 185 cases. The New Employee
      model became more economical than the Fully Outsourced model when the annual
      caseload exceeded 110 cases. The Cross-Trained model was the most economical when
      annual caseload exceeded 55 cases. IMPLICATIONS: Cross-training an employee as a
      cell salvage technician is more economical than outsourcing when caseload exceeds
      55 per year.

PMID- 14693620
TI  - Capnography in non-tracheally intubated emergency patients as an additional tool
      in pulse oximetry for prehospital monitoring of respiration.
AB  - Victims of minor trauma transported by paramedic-based rescue systems are usually
      monitored with pulse oximetry. Under the difficult surroundings of prehospital
      trauma care, pulse oximeters show considerable periods of malfunction. We tested
      the hypothesis that capnography is a good, easy to use tool for monitoring in
      nonintubated trauma victims. Seventy nonintubated trauma victims were included in
      this study. Vital variables and number and time of malfunctions were sampled for
      oximeter and capnometer recordings. Total number of alerts (63 versus 10), number
      of alerts per patient (3.3 [1.9] versus 0.3 [0.9]) (mean [SD]), total time of
      malfunction (191.5 [216.7] s versus 11.8 [40.2] s), time of malfunction per alarm
      (58.3 [71.4] s versus 5.5 [14.6] s), and the percentage of malfunction time
      during transport (13.2% [15.3%] versus 0.8% [2.8%]) differed significantly (P <
      0.01) between oximetry and capnography. Although pulse oximetry is a standard
      method of monitoring in emergency care, we found capnography to be helpful as a
      monitoring device. We consequently recommend the use of capnography on transport
      as an additional monitoring tool to reduce periods lacking supervision of the
      vital variables. IMPLICATIONS: Capnography is a useful tool to improve
      respiratory monitoring in nonintubated trauma victims on emergency transport and
      an easy to use supplement to pulse oximetry.

PMID- 14693621
TI  - Ventilation-perfusion distribution related to different inspiratory flow patterns
      in experimental lung injury.
AB  - In acute lung injury (ALI), controlled mechanical ventilation with decelerating
      inspiratory flow (.V(dec)) has been suggested to improve oxygenation when
      compared with constant flow (.V(con)) by improving the distribution of
      ventilation and perfusion (.V(A)/.Q). We performed the present study to test this
      hypothesis in an animal model of ALI. Furthermore, the effects of combined
      decelerating and constant flow (Vdot;(deco)) were evaluated. Thus, 18 pigs with
      experimental ALI were randomized to receive mechanical ventilation with either
      .V(con), .V(dec) or a fixed combination of both flow wave forms (.V(deco)) at the
      same tidal volume and positive end-expiratory pressure level for 6 h.
      Hemodynamics, gas exchange, and .V(A)/.Q distribution were determined. The
      results revealed an improvement of oxygenation resulting from a decrease of
      pulmonary shunt within each group (P < 0.05). However, blood flow to lung areas
      with a normal .V(A)/.Q distribution increased only during ventilation with
      .V(con) (P < 0.05). Accordingly, PaO(2) was higher with .V(con) than with .V(dec)
      and .V(deco) (P < 0.05). We conclude that contrary to the hypothesis,
      .V(con)provides a more favorable .V(A)/.Q distribution, and hence better
      oxygenation, when compared with .V(dec) and .V(deco) in this model of ALI.
      IMPLICATIONS: In acute lung injury, mechanical ventilation with decelerating flow
      has been suggested to improve ventilation-perfusion distribution when compared
      with constant flow. We tested this hypothesis in an animal model. Contrary to the
      hypothesis, we found a more favorable ventilation-perfusion distribution during
      constant flow when compared with decelerating flow.

PMID- 14693623
TI  - Korean hand acupressure for motion sickness in prehospital trauma care: a
      prospective, randomized, double-blinded trial in a geriatric population.
AB  - Patients with trauma or medical illnesses transported to the hospital by
      ambulance have a frequent incidence of motion sickness. Because the
      administration of drugs in the ambulance is prohibited by law in Austria, the
      noninvasive Korean hand acupressure point at K-K9 may be an alternative against
      nausea and vomiting. We enrolled 100 geriatric patients with minor trauma,
      randomizing them into a K-K9 group and a sham acupressure group. We recorded
      visual analog scores (VAS) for nausea and for the patient's overall satisfaction
      with the treatment, hemodynamic variables, and peripheral vasoconstriction. In
      the K-K9 group, a significant (P < 0.01) increase in nausea was recorded in all
      cases: from VAS of 0 mm to 25 +/- 6 mm. A similarly significant (P < 0.01)
      increase was registered in the sham group: from VAS of 0 mm to 83 +/- 8 mm.
      However, at the time of arrival in the hospital, nausea scores were significantly
      different between the K-K9 group and the sham group (P < 0.01). Although all
      patients had been vasoconstricted at the emergency site before treatment, there
      was a significant difference (P < 0.01) between groups with regard to the number
      of vasoconstricted patients at the hospital (4 and 46 constricted and dilated,
      respectively, in the K-K9 group versus 48 and 2 constricted and dilated,
      respectively, in the sham group). On arrival in the hospital, a significant
      difference (P < 0.01) in heart rate was noted between the K-K9 group and the sham
      group (65 +/- 6 bpm versus 98 +/- 8 bpm). The patients' overall satisfaction with
      the provided care was significantly higher (P < 0.01) in the K-K9 group (19 +/- 9
      mm VAS) than in the sham group (48 +/- 12 mm VAS). Neither group experienced a
      significant change in blood pressure. K-K9 stimulation was an effective and
      simple treatment for nausea during emergency care and significantly improved
      patient satisfaction. IMPLICATIONS: Korean hand acupressure at the K-K9 point was
      effective in reducing nausea and subjective symptoms of motion sickness in
      emergency trauma transport of patients at high risk of motion sickness.

PMID- 14693624
TI  - The effects of prolonged ambulation on labor with epidural analgesia.
AB  - Ambulation during labor is becoming more popular, although its impact on the
      progress of labor and on pain intensity remains unclear. We wondered whether
      prolonged ambulation with epidural analgesia had a possible effect on duration of
      labor and pain. In this prospective, randomized trial, 61 parturients with
      uncomplicated term pregnancies were allocated to be recumbent (n = 31) or to
      ambulate (n = 30). Epidural analgesia was provided with intermittent
      administrations of 0.08% bupivacaine-epinephrine plus 1 microg/mL of sufentanil.
      Of the 30 women assigned to the ambulatory group, 25 actually walked. Their
      ambulating time was 64 +/- 34 min (mean +/- SD), i.e., 29% +/- 16% of the first
      stage. There were no differences between the two groups in the length of labor
      and in pain visual analog scale scores. However, the ambulatory group received
      smaller doses of bupivacaine (6.4 +/- 2.2 mg/h versus 8.4 +/- 3.6 mg/h; P = 0.01)
      and of oxytocin (6.0 +/- 3.7 mUI/min versus 10.2 +/- 8.8 mUI/min; P < 0.05). A
      greater ability to void was also found in the ambulatory group (P < 0.01).
      Although the duration of labor and pain relief was unchanged, these findings
      support that ambulation during labor may be advantageous. IMPLICATIONS: This
      study compared the duration of labor and pain relief between parturients
      receiving epidural analgesia who were ambulated or were recumbent. Whereas
      walking had no impact on either duration of labor or pain relief, it was
      associated with a reduction in both bupivacaine and oxytocin requirements.

PMID- 14693625
TI  - Intrathecal meperidine decreases shivering during cesarean delivery under spinal
      anesthesia.
AB  - Shivering associated with spinal anesthesia is uncomfortable and may interfere
      with monitoring. We performed this prospective, double-blinded, and randomized
      study to determine whether intrathecal meperidine (0.2 mg/kg) decreases the
      incidence and intensity of shivering after spinal anesthesia for cesarean
      delivery. Forty parturients scheduled for nonemergent cesarean delivery were
      enrolled in two groups. Spinal anesthesia consisted of hyperbaric bupivacaine
      (0.75%; 10.5 mg), morphine 0.15 mg, and, in the experimental group, meperidine
      (0.2 mg/kg) or, in the control group, normal saline. Data collection, including
      sensory block level, blood pressure, core temperature, and shivering intensity,
      was performed every minute for 10 min, every 3 min for 33 min, and then every 5
      min until the sensory level receded to L4. Time to highest sensory level, maximum
      number of blocked segments, sensory and motor blockade regression, and systolic
      blood pressure showed no difference between groups. The incidence of shivering
      was less (P < 0.02) in the meperidine group, as was its intensity (P < 0.003).
      Intrathecal meperidine (0.2 mg/kg) is effective in reducing the incidence and
      intensity of shivering associated with spinal anesthesia for cesarean delivery.
      IMPLICATIONS: Previous studies have suggested that IV meperidine is helpful for
      treating intraoperative shivering. This study was undertaken to evaluate spinal
      meperidine and found that it decreases the incidence and intensity of shivering
      associated with spinal anesthesia for cesarean delivery.

PMID- 14693626
TI  - A comparison of duration of analgesia of intrathecal 2.5 mg of bupivacaine,
      ropivacaine, and levobupivacaine in combined spinal epidural analgesia for
      patients in labor.
AB  - We assessed the duration of labor analgesia rendered by intrathecal (IT) local
      anesthetics as the sole drugs. In this randomized, controlled, and double-blinded
      study, labor analgesia was induced using combined spinal-epidural technique in 60
      ASA physical status I nulliparous parturients with IT bupivacaine 2.5 mg (group
      B), ropivacaine 2.5 mg (group R), or levobupivacaine 2.5 mg (group L). Pain
      scores (0-100 visual analog scale) and blood pressure were recorded pre-block and
      for the first 30 min post-block. The degree of motor block and the highest
      sensory block were also monitored. The duration of analgesia (our primary
      outcome) was the longest in group B but was similar between groups R and L (mean
      +/- SE, 76.3 +/- 5.9 min versus 52.6 +/- 4.0 min and 51.5 +/- 3.4 min,
      respectively, P < 0.05). Group B had the most frequent incidence of lower limb
      motor block but there was no difference between groups R and L (5 of 20
      parturients versus 2 of 20 and 0 of 20, respectively, P < 0.05). The profile of
      the other side effects was indistinguishable between the groups. With the current
      regimen, IT bupivacaine produced the longest duration of labor analgesia.
      IMPLICATIONS: Intrathecal 2.5 mg bupivacaine significantly prolongs the duration
      of analgesia in laboring patients compared with ropivacaine or levobupivacaine.
      This suggests that, at clinically relevant doses, bupivacaine may have greater
      potency.

PMID- 14693627
TI  - Risperidone and exaggerated hypotension during a spinal anesthetic.
AB  - Antipsychotic medications are often continued through pregnancy and may have
      important anesthetic interactions. For example, risperidone is an antipsychotic
      medication with therapeutic effects mediated by dopaminergic and serotonergic
      antagonism. However, it also possesses potent alpha-1 adrenergic antagonism. Here
      we report a case of a parturient with bipolar disease, controlled with lithium
      and risperidone, undergoing a spinal anesthetic for a cesarean delivery. The
      parturient developed exaggerated hypotension, refractory to conventional
      treatment with ephedrine and IV fluids, that eventually responded to large doses
      of phenylephrine. Risperidone alpha-antagonism should be a consideration for any
      patient receiving this medication during neuraxial anesthesia. Treatment of
      significant and refractory hypotension with an alpha-1 agonist such as
      phenylephrine may be warranted. IMPLICATIONS: Parturients receiving neuraxial
      blocks may be taking antipsychotic medications. Although the therapeutic effects
      of antipsychotic medications are mediated by dopaminergic and serotonergic
      antagonism, many possess alpha-adrenergic antagonist properties. We report a case
      of exaggerated hypotension during a spinal anesthetic for cesarean delivery that
      may have been a result of the alpha-adrenergic antagonism of risperidone.

PMID- 14693628
TI  - The effects of three different approaches on the onset time of sciatic nerve
      blocks with 0.75% ropivacaine.
AB  - We studied three different injection techniques of sciatic nerve block in terms
      of block onset time and efficacy with 0.75% ropivacaine. A total of 75 patients
      undergoing foot surgery were randomly allocated to receive sciatic nerve blockade
      by means of the classic posterior approach (group classic; n = 25), a modified
      subgluteus posterior approach (group subgluteus; n = 25), or a lateral popliteal
      approach (group popliteal; n = 25). All blocks were performed with the use of a
      nerve stimulator (stimulation frequency, 2 Hz; intensity, 2-0.5 mA) and 30 mL of
      0.75% ropivacaine. Onset of nerve block 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. In the three groups, an appropriate
      sciatic stimulation was elicited at <0.5 mA. The failure rate was similar in the
      three groups (group popliteal: 4% versus group classic: 4% versus group
      subgluteus: 8%). The onset of nerve block was slower in group popliteal (25 +/- 5
      min) compared with group classic (16 +/- 4 min) and group subgluteus (17 +/- 4
      min; P < 0.001). There was no significant difference in the onset of nerve block
      between group classic and group subgluteus. No differences in the degree of pain
      measured at the first postoperative administration of pain medication were
      observed among the three groups. We conclude that the three approaches resulted
      in clinically acceptable anesthesia in the distribution of the sciatic nerve. The
      subgluteus and classic posterior approaches generated a significantly faster
      onset of anesthesia than the lateral popliteal approach. IMPLICATIONS: Comparing
      three different approaches to the sciatic nerve with 0.75% ropivacaine, the
      classic and subgluteal approaches exhibited a faster onset time of sensory and
      motor blockade than the lateral popliteal approach.

PMID- 14693630
TI  - A novel infraclavicular brachial plexus block: the lateral and sagittal
      technique, developed by magnetic resonance imaging studies.
AB  - A new infraclavicular brachial plexus block method has the patient supine with an
      adducted arm. The target is any of the three cords behind the pectoralis minor
      muscle. The point of needle insertion is the intersection between the clavicle
      and the coracoid process. The needle is advanced 0 degrees -30 degrees posterior,
      always strictly in the sagittal plane next to the coracoid process while abutting
      the antero-inferior edge of the clavicle. We tested the new method using magnetic
      resonance imaging (MRI) in 20 adult volunteers, without inserting a needle.
      Combining 2 simulated needle directions by 15 degrees posterior and 0 degrees in
      the images of the volunteers, at least one cord in 19 of 20 volunteers was
      contacted. This occurred within a needle depth of 6.5 cm. In the sagittal plane
      of the method the shortest depth to the pleura among all volunteers was 7.5 cm.
      The MRI study indicates that the new infraclavicular technique may be efficient
      in reaching a cord of the brachial plexus, often not demanding more than two
      needle directions. The risk of pneumothorax should be minimal because the needle
      is inserted no deeper than 6.5 cm. However, this needs to be confirmed by a
      clinical study. IMPLICATIONS: A new infraclavicular brachial plexus block method
      was investigated using magnetic resonance imaging without inserting needles in
      the volunteers. The study suggests two needle directions for performance of the
      block and that the risk of lung injury should be minimal. Expectations need to be
      confirmed by a clinical study.

PMID- 14693629
TI  - Quantitative and selective evaluation of differential sensory nerve block after
      transdermal lidocaine.
AB  - We evaluated the effect of transdermal lidocaine on differential sensory nerve
      block in 15 healthy volunteers. Lidocaine 10% gel was applied topically to a
      forearm and covered with a plastic film. Three types of sensory nerve fibers
      (Abeta, Adelta, and C fibers) were evaluated with a series of 2000-, 250-, and 5
      Hz stimuli using current perception threshold (CPT) testing. Sensations of touch,
      pinprick, cold, and warmth were also measured. These measurements were made
      before the topical lidocaine (baseline), 60 min after the draping (T0), and at 1
      h intervals until 5 h after T0 (T1 to T5). A significant increase in CPT compared
      with baseline was observed until T2 at 5 Hz and T4 at 250 Hz, whereas the
      increase in CPT at 2000 Hz continued throughout the study period. All subjects
      experienced the disappearance of pinprick and cold sensations, whereas touch and
      warmth sensations were detectable during the study period. We conclude that when
      lidocaine is applied transdermally, the sensitivity of nerves to local
      anesthetics is proportional to the axon diameters. However, pinprick and cold
      sensation are affected more strongly than other sensations at receptor sites.
      IMPLICATIONS: We evaluated the effect of transdermal lidocaine on differential
      sensory nerve block in healthy volunteers. Our results show that the sensitivity
      of nerves to local anesthetics is proportional to the axon diameter.

PMID- 14693632
TI  - Administration of 100% oxygen before removal of the laryngeal mask airway does
      not affect postanesthetic arterial partial pressure of oxygen.
AB  - Breathing 100% oxygen at the end of general anesthesia has been shown to worsen
      postoperative pulmonary gas exchange when an endotracheal tube is used. Counter
      measures, such as high positive end-expiratory pressure or the vital-capacity
      maneuver, may limit this effect. Such strategies, however, may be impracticable,
      or even contraindicated, when the laryngeal mask airway (LMA) is used. Because of
      the vast differences in design between the LMA and endotracheal tube, we examined
      postanesthetic blood gas tensions in patients after emergence from anesthesia
      breathing oxygen via LMA. Sixty-four ASA physical status I-II patients undergoing
      general anesthesia for 60 min with LMA were randomly assigned to receive either
      100% or 30% oxygen during emergence from anesthesia and removal of LMA.
      Postoperative blood gas measurements were taken at 30 and 60 min after removal of
      the LMA. At either measurement, patients treated with 100% oxygen essentially had
      the same arterial partial pressure of oxygen (60-min measurement: 83 +/- 8 versus
      85 +/- 7 mm Hg [mean +/- SD], P = 0.14) as those treated with 30% oxygen. We
      conclude that breathing 100% oxygen at the end of general anesthesia does not
      worsen postoperative pulmonary gas exchange when an LMA is used. IMPLICATIONS:
      The endotracheal tube and laryngeal mask airway are substantially different
      artificial airways used to ventilate the lungs of anesthetized patients.
      Breathing 100% oxygen before removing the endotracheal tube results in lung
      function defects. This study shows that oxygen breathing before removing the
      laryngeal mask airway has no effect on pulmonary function.

PMID- 14693633
TI  - Mechanical versus manual ventilation via a face mask during the induction of
      anesthesia: a prospective, randomized, crossover study.
AB  - One approach to make ventilation safer in an unprotected airway has been to limit
      tidal volumes; another one might be to limit peak airway pressure, although it is
      unknown whether adequate tidal volumes can be delivered. Accordingly, the purpose
      of this study was to evaluate the quality of automatic pressure-controlled
      ventilation versus manual circle system face-mask ventilation regarding
      ventilatory variables in an unprotected airway. We studied 41 adults (ASA status
      I-II) in a prospective, randomized, crossover design with both devices during the
      induction of anesthesia. Respiratory variables were measured with a pulmonary
      monitor (CP-100). Pressure-controlled mask ventilation versus circle system
      ventilation resulted in lower (mean +/- SD) peak airway pressures (10.6 +/- 1.5
      cm H(2)O versus 14.4 +/- 2.4 cm H(2)O; P < 0.001), delta airway pressures (8.5 +/
      1.5 cm H(2)O versus 11.9 +/- 2.3 cm H(2)O; P < 0.001), expiratory tidal volume
      (650 +/- 100 mL versus 680 +/- 100 mL; P = 0.001), minute ventilation (10.4 +/-
      1.8 L/min versus 11.6 +/- 1.8 L/min; P < 0.001), and peak inspiratory flow rates
      (0.81 +/- 0.06 L/s versus 1.06 +/- 0.26 L/s; P < 0.001) but higher inspiratory
      time fraction (48% +/- 0.8% versus 33% +/- 7.7%; P < 0.001) and end-tidal carbon
      dioxide (34 +/- 3 mm Hg versus 33 +/- 4 mm Hg; not significant). We conclude that
      in this model of apneic patients with an unprotected airway, pressure-controlled
      ventilation resulted in reduced inspiratory peak flow rates and peak airway
      pressures when compared with circle system ventilation, thus providing an
      additional patient safety effect during mask ventilation. IMPLICATIONS: In this
      model of apneic patients with an unprotected airway, pressure-controlled
      ventilation resulted in reduced inspiratory peak flow rates and lower peak airway
      pressures when compared with circle system ventilation, thus providing an
      additional patient safety effect during face-mask ventilation.

PMID- 14693634
TI  - Use of an elevation pillow to produce the head-elevated laryngoscopy position for
      airway management in morbidly obese and large-framed patients.

PMID- 14693635
TI  - Ondansetron for prevention of intrathecal opioids-induced pruritus, nausea and
      vomiting after cesarean delivery.

PMID- 14693636
TI  - Intramucosal pH measurements for extremely obese patients during laparoscopic
      bariatric surgery.

PMID- 14693637
TI  - Pharmacologic therapy of acute pulmonary embolism.

PMID- 14693638
TI  - The cost comparison of infraclavicular brachial plexus block by nerve stimulator
      and ultrasound guidance.

PMID- 14693639
TI  - Is there a need for a recruiting strategy in morbidly obese patients undergoing
      laparoscopic surgery?

PMID- 14693640
TI  - More conclusive large-scale trials necessary before recommending use of beta
      blockade in patients at risk.

PMID- 14693641
TI  - Successful lung isolation with one bronchial blocker in a patient with tracheal
      bronchus.

PMID- 14693642
TI  - Stewart approach is not always a practical clinical tool.

PMID- 14693643
TI  - Tracheal intubation in obese patients.

PMID- 14693644
TI  - Mivacurium and bronchospasm.

PMID- 14693645
TI  - Thoracic epidural catheter placement in infants via the caudal approach under
      electrocardiographic guidance: simplification of the original technique.

PMID- 14693646
TI  - Pharmacologic therapy of pulmonary vasoconstriction in acute pulmonary embolism.

PMID- 14693647
TI  - Comparison between level 1 and rapid infusion system.

PMID- 14693648
TI  - Assessment of pain during venous puncture using a visual analog scale and
      problems associated with prolonged attachment of the lidocaine patch (PENLES).

PMID- 14693649
TI  - Smaller dose of 0.5 mg/kg IV ketorolac is sufficient to provide pain relief in
      children.

PMID- 14693650
TI  - Tranexamic acid and coronary surgery.

PMID- 14693651
TI  - Dueling fiberoptic bronchoscope techniques.

PMID- 14693652
TI  - Validation of the BIS monitor during conscious sedation and deep sedation in
      children.

PMID- 14693653
TI  - Stroke volume variation as an indicator of fluid responsiveness.

PMID- 14693654
TI  - Pooled analysis of alcohol dehydrogenase genotypes and head and neck cancer: a
      HuGE review.
AB  - Possession of the fast metabolizing alleles for alcohol dehydrogenase (ADH),
      ADH1B*2 and ADH1C*1, and the null allele for aldehyde dehydrogenase (ALDH),
      ALDH2*2, results in increased acetylaldehyde levels and is hypothesized to
      increase the risk of head and neck cancer. To examine this association, the
      authors undertook a Human Genome Epidemiology review on these three genes and a
      pooled analysis of published studies on ADH1C. The majority of Asians had the
      fast ADH1B*2 and ADH1C*1 alleles, while the majority of Caucasians had the slow
      ADH1B*1/1 and ADH1C*1/2 genotypes. The ALDH2*2 null allele was frequently
      observed among Asians, though it was rarely observed in other populations. In a
      pooled analysis of data from seven case-control studies with a total of 1,325
      cases and 1,760 controls, an increased risk of head and neck cancer was not
      observed for the ADH1C*1/2 genotype (odds ratio = 1.00, 95% confidence interval:
      0.81, 1.23) or the ADH1C*1/1 genotype (odds ratio = 1.14, 95% confidence
      interval: 0.92, 1.41). Increased relative risks of head and neck cancer were
      reported for the ADH1B*1/1 and ALDH2*1/2 genotypes in several studies.
      Recommendations for future studies include larger sample sizes and incorporation
      of relevant ADH and ALDH genes simultaneously, as well as other genes. These
      considerations suggest the potential for the organization of a consortium of
      investigators conducting studies in this field.

PMID- 14693655
TI  - Flexible matching in case-control studies of gene-environment interactions.
AB  - Because of the lack of power of case-control study designs to detect gene
      environment interactions, flexible matching has recently been proposed as a
      method of improving efficiency. In this paper, the authors consider a large
      sample approximation method that allows estimation of the most efficient matching
      strategy when genotype and exposure are either independent or associated. The
      authors provide tables of the sample sizes required to detect gene-environment
      interactions if this flexible matching strategy is followed, and they make brief
      comparisons with other study designs.

PMID- 14693656
TI  - Risk of uncomplicated peptic ulcer among users of aspirin and nonaspirin
      nonsteroidal antiinflammatory drugs.
AB  - The association between nonsteroidal antiinflammatory drugs (NSAIDs) and upper
      gastrointestinal complications is well documented. However, epidemiologic data on
      the risk of clinically symptomatic but uncomplicated peptic ulcer are quite
      limited. The authors studied the association between prescription NSAIDs and the
      risk of symptomatic ulcer in a population-based cohort of 458,840 persons and
      1,167,469 person-years in the United Kingdom between 1995 and 1999 and conducted
      a nested case-control analysis of 1,197 cases and 10,000 controls. The relative
      risk and 95% confidence intervals were estimated and adjusted for several factors
      known to be associated with gastrointestinal damage. The incidence rate of
      symptomatic ulcer was 1.03 (95% confidence interval (CI): 0.97, 1.08) cases per
      1,000 person-years. Compared with nonusers, the relative risk was 2.9 (95% CI:
      2.3, 3.6) for aspirin and 4.0 (95% CI: 3.2, 5.1) for nonaspirin NSAID users. For
      aspirin users, the relative risk was similar for doses up to 300 mg daily and for
      both gastric and duodenal ulcers. For nonaspirin NSAIDs, the relative risk was
      2.6 (95% CI: 2.0, 3.5) for medium daily doses or lower and 4.9 (95% CI: 3.8, 6.5)
      for high daily doses; it was 5.6 (95% CI: 3.9, 8.2) for gastric and 3.1 (95% CI:
      2.3, 4.2) for duodenal ulcers. The risk of symptomatic ulcer for aspirin and
      nonaspirin NSAIDs was elevated throughout treatment. These findings suggest that
      NSAIDs might not only complicate but also originate clinically relevant peptic
      ulcers.

PMID- 14693657
TI  - Antioxidants, carotenoids, and risk of rectal cancer.
AB  - Numerous properties suggest that antioxidants and carotenoids may be valuable
      chemopreventive agents. A population-based case-control study of 952 rectal
      cancer cases and 1,205 controls from Northern California and Utah was conducted
      between September 1997 and February 2002. Detailed diet history, medical history,
      and lifestyle factors interviews were conducted. Dietary antioxidants were not
      associated with rectal cancer risk in men. For women, relative to the highest
      level of intake, low intake of dietary lycopene (odds ratio (OR) = 1.7, 95%
      confidence interval (CI): 1.0, 2.8) or vitamin E (OR = 2.2, 95% CI: 1.1, 4.3) was
      associated with an increased risk of rectal cancer. Alpha-, beta-, and gamma
      tocopherol were associated with an approximate twofold increased risk of rectal
      cancer in women. Associations were stronger for women aged > or = 60 years for
      vitamin E and tocopherols (alpha-tocopherol OR = 3.6, 95% CI: 1.4, 9.4; gamma
      tocopherol OR = 5.3, 95% CI: 2.1, 13.2; delta-tocopherol OR = 1.9, 95% CI: 0.9,
      4.0), except for beta-tocopherol, for which risk increased twofold for all women.
      Associations differed by estrogen status for beta-carotene, lycopene, and vitamin
      E. These results suggest that vitamin E and lycopene may modestly reduce the risk
      of rectal cancer in women.

PMID- 14693658
TI  - History of urinary tract infection and risk of renal cell carcinoma.
AB  - Limited data exist regarding whether a history of urinary tract infection (UTI)
      increases risk of developing renal cell carcinoma (RCC). Furthermore, it is
      unclear whether any association of RCC with a history of UTIs is modified by
      known risk factors for RCC (i.e., smoking, obesity). The authors report data from
      a 1986-1989 population-based case-control study in Iowa. RCC cases (233 males,
      139 females) were identified through the Iowa Cancer Registry; controls (1,497
      males, 751 females) were randomly selected from the general population, frequency
      matched on age and sex. Subjects provided detailed information on demographic,
      anthropometric, lifestyle, dietary, and medical history risk factors. In age
      adjusted analysis, risk increased for subjects who self-reported a history of
      physician-diagnosed kidney or bladder infection (odds ratio (OR) = 1.9, 95%
      confidence interval (CI): 1.5, 2.5) compared with those reporting no such
      history. Both sex and smoking status modified the risk of RCC associated with a
      history of UTI, with the strongest risk reported for males (OR = 2.7, 95% CI:
      1.9, 3.8) and current smokers (OR = 4.3, 95% CI: 2.7, 6.7). The strongest risk
      was reported for male current smokers with a history of UTI (OR = 9.7, 95% CI:
      5.0, 18.1). Multivariate adjustment for anthropometric, lifestyle, and dietary
      factors did not alter these findings. Results suggest a positive association of
      UTI history with RCC development, with elevated risks most notable for males with
      a history of smoking.

PMID- 14693659
TI  - Association of in utero exposure to maternal smoking with reduced semen quality
      and testis size in adulthood: a cross-sectional study of 1,770 young men from the
      general population in five European countries.
AB  - Between 1996 and 1999, the authors invited all young men from five European
      countries who were undergoing compulsory medical examination for possible
      military service to participate in a study on male reproductive health. The
      participation rate was 19% in two cities in Denmark (n = 889), 17% in Oslo,
      Norway (n = 221), 13% in Turku, Finland (n = 313), 14% in Kaunas, Lithuania (n =
      157), and 19% in Tartu, Estonia (n = 190). Each man provided a semen sample, was
      examined by a physician, and, in collaboration with his mother, completed a
      questionnaire about general and reproductive health, current smoking habits, and
      exposure to smoking in utero. After adjustment for confounding factors, men
      exposed to smoking in utero had a reduction in sperm concentration of 20.1% (95%
      confidence interval (CI): 6.8, 33.5) and a reduction in total sperm count of
      24.5% (95% CI: 9.5, 39.5) in comparison with unexposed men. Percentages of motile
      and morphologically normal sperm cells were 1.85 (95% CI: 0.46, 3.23) and 0.64
      (95% CI: -0.02, 1.30) percentage points lower, respectively, among men exposed in
      utero, and exposed men had a 1.15-ml (95% CI: 0.66, 1.64) smaller testis size.
      The associations were present when data from the study centers were analyzed
      separately (though not in Lithuania, where only 1% of mothers smoked during
      pregnancy), although the strength of the association varied. Maternal smoking may
      have long-term implications for the reproductive health of the offspring. This is
      another good reason to advise pregnant women to avoid smoking.

PMID- 14693660
TI  - Preterm delivery rates in North Carolina: are they really declining among non
      Hispanic African Americans?
AB  - The preterm delivery rate in North Carolina is consistently higher than the
      national average. However, recent reports suggest that singleton preterm delivery
      rates for non-Hispanic Whites are increasing while those for non-Hispanic African
      Americans are decreasing. To study this pattern further, the authors examined
      data on singleton non-Hispanic White and non-Hispanic African-American births in
      1989 and 1999 by using North Carolina vital statistics data. They found that the
      frequency of preterm delivery rose 1.1% (8.5% to 9.6%) among non-Hispanic Whites
      but declined 1.4% (17.9% to 16.5%) among non-Hispanic African Americans over the
      same time period. For both subgroups, a bimodal distribution of birth weights was
      apparent among preterm births at 28-31 weeks of gestation. The second peak with
      its cluster of normal-weight infants was more prominent among non-Hispanic
      African Americans in 1989 than in 1999. To reduce the potential for bias due to
      misclassification of infant gestational age, frequencies of preterm delivery of
      infants who weighed less than 2,500 g were calculated. Unlike the original
      analysis, this calculation showed that preterm delivery increased for both
      subgroups. A number of non-Hispanic African-American births classified as preterm
      were apparently term births mistakenly assigned short gestational ages. Such
      misclassification was more frequent in 1989 than in 1999, inflating 1989 preterm
      delivery rates.

PMID- 14693661
TI  - Spatial patterns of infant mortality in Mali: the effect of malaria endemicity.
AB  - A spatial analysis was carried out to identify factors related to geographic
      differences in infant mortality risk in Mali by linking data from two spatially
      structured databases: the Demographic and Health Surveys of 1995-1996 and the
      Mapping Malaria Risk in Africa database for Mali. Socioeconomic factors measured
      directly at the individual level and site-specific malaria prevalence predicted
      for the Demographic and Health Surveys' locations by a spatial model fitted to
      the Mapping Malaria Risk in Africa database were examined as possible risk
      factors. The analysis was carried out by fitting a Bayesian hierarchical
      geostatistical logistic model to infant mortality risk, by Markov chain Monte
      Carlo simulation. It confirmed that mother's education, birth order and interval,
      infant's sex, residence, and mother's age at infant's birth had a strong impact
      on infant mortality risk in Mali. The residual spatial pattern of infant
      mortality showed a clear relation to well-known foci of malaria transmission,
      especially the inland delta of the Niger River. No effect of estimated parasite
      prevalence could be demonstrated. Possible explanations include confounding by
      unmeasured covariates and sparsity of the source malaria data. Spatial
      statistical models of malaria prevalence are useful for indicating approximate
      levels of endemicity over wide areas and, hence, for guiding intervention
      strategies. However, at points very remote from those sampled, it is important to
      consider prediction error.

PMID- 14693662
TI  - Dietary fat and the risk of clinical type 2 diabetes: the European prospective
      investigation of Cancer-Norfolk study.
AB  - The role of dietary fat in the etiology of type 2 diabetes remains uncertain. The
      authors investigated the association between dietary fat composition and risk of
      clinical type 2 diabetes in the European Prospective Investigation of Cancer
      Norfolk study and identified food consumption patterns associated with dietary
      fat composition. Diet was assessed at baseline (1993-1997) using a
      semiquantitative food frequency questionnaire. From multiple sources of
      information, 414 incident cases of diabetes were identified among 23,631 men and
      women aged 40-78 years during 3-7 years of follow-up. The capture-recapture
      ascertainment level was 99%. The energy-adjusted dietary
      polyunsaturated:saturated fat ratio was inversely associated with the risk of
      diabetes (odds ratio (OR) = 0.84 per standard deviation change, 95% confidence
      interval (CI): 0.75, 0.94). Adjustment for age, sex, family history of diabetes,
      smoking, physical activity, total fat, protein, and alcohol attenuated the
      association (OR = 0.88, 95% CI: 0.78, 0.99), and it was no longer statistically
      significant after including body mass index and the waist:hip ratio (OR = 0.91,
      95% CI: 0.81, 1.03). This prospective study showed that an increased dietary
      polyunsaturated:saturated fat ratio was associated with a reduced risk of
      diabetes, independent of age, sex, family history of diabetes, and other
      lifestyle factors.

PMID- 14693663
TI  - VITamins And Lifestyle cohort study: study design and characteristics of
      supplement users.
AB  - Vitamin and mineral supplements are among the most commonly used drugs in the
      United States, despite limited evidence on their benefits or risks. This paper
      describes the design, implementation, and participant characteristics of the
      VITamins And Lifestyle (VITAL) Study, a cohort study of the associations of
      supplement use with cancer risk. A total of 77,738 men and women in western
      Washington State, aged 50-76 years, entered the study in 2000-2002 by completing
      a detailed questionnaire on supplement use, diet, and other cancer risk factors,
      and 70% provided DNA through self-collected buccal cell specimens. Supplement
      users were targeted in recruitment: 66% used multivitamins, 46% used individual
      vitamin C, 47% used individual vitamin E, and 46% used calcium, typically for 5-8
      of the past 10 years. Analyses to identify confounding factors, the main study
      limitation, showed that regular nonsteroidal anti-inflammatory drug use, intake
      of fruits and vegetables, and recreational physical activity were strongly
      associated with supplement use (p < 0.001). The authors describe a follow-up
      system in which cancers, deaths, and changes of residence are tracked
      efficiently, primarily through linkage to public databases. These methods may be
      useful to other researchers implementing a large cohort study or designing a
      passive follow-up system.

PMID- 14693664
TI  - Response rates to a questionnaire 26 years after baseline examination with
      minimal interim participant contact and baseline differences between respondents
      and nonrespondents.
AB  - Research on response rates to surveys mailed to study participants decades after
      baseline examination, with minimal interim contact, is limited. This paper
      documents response rates to a 26-year follow-up survey of surviving participants
      from a large cohort in Illinois and compares baseline characteristics of
      nonrespondents and respondents. Mortality follow-up of the Chicago Heart
      Association Detection Project in Industry 1967-1973 cohort involved minimal or no
      participant contact since baseline. In 1996, a 26-year follow-up questionnaire
      was mailed to all surviving participants aged 65 years or older. Current
      addresses were obtained from the Health Care Financing Administration for 96.5
      percent of 12,409 participants in our analyses. Total response rates were 59.8
      percent and, for participants for whom Health Care Financing Administration
      addresses were available, 60.8 percent. A higher response rate was obtained for
      younger recipients, men, Whites, more-educated persons, nonsmokers, and those
      with a better cardiovascular risk profile at baseline. A graded negative relation
      was found between number of cardiovascular risk factors at baseline and response
      rates obtained in 1996. Use of Health Care Financing Administration records as an
      additional follow-up method and factors that influence response rates are
      discussed. In conclusion, long-term follow-up of older surviving participants is
      feasible if current addresses can be obtained from standardized sources.

PMID- 14693666
TI  - Re: "epidemiology of salmonellosis in California, 1990-1999: morbidity,
      mortality, and hospitalization costs".

PMID- 14693667
TI  - Design and use of highly specific substrates of neutrophil elastase and
      proteinase 3.
AB  - We have exploited differences in the structures of S2' subsites of proteinase 3
      (Pr3) and human neutrophil elastase (HNE) to prepare new fluorogenic substrates
      specific for each of these proteases. The positively charged residue at position
      143 in Pr3 prevents it from accommodating an arginyl residue at S2' and improves
      the binding of P2' aspartyl-containing substrates, as judged by the decreased
      K(m). As a result, the k(cat)/K(m) for Abz-VADCADQ-EDDnp is over 500 times
      greater for Pr3 than for HNE, and that for Abz-APEEIMRRQ-EDDnp is over 500 times
      greater for HNE than for Pr3. This allows each protease activity to be measured
      in the presence of a large excess of the other, as might occur in vivo. Placing a
      prolyl residue in position P2' greatly impaired substrate binding to both HNE and
      Pr3, which further emphasizes the importance of S' subsites in these proteases.
      HNE and Pr3 activities were measured with these substrates at the surface of
      fixed polymorphonuclear leukocytes (PMNs) before and after activation. This
      demonstrated that their active site remains accessible when they are exposed to
      the cell surface. Both membrane-bound proteases were strongly inhibited by low
      M(r) serine protease inhibitors, but only partially by inhibitors of larger M(r)
      such as alpha1-protease inhibitor, the main physiologic inhibitor in lung
      secretions. Most of membrane-bound HNE and Pr3 can be released from the membrane
      surface of fixed cells by a buffer containing detergent, suggesting that
      hydrophobic interactions are involved in membrane binding.

PMID- 14693668
TI  - CD40 plays a crucial role in lipopolysaccharide-induced acute lung injury.
AB  - Activated alveolar macrophages (AMphi) are known to constitute a critical
      modulator of the lung inflammatory response through the production of various
      mediators. However, the role of activated AMphi in acute lung injury (ALI) and
      acute respiratory distress syndrome is less well known. To address this issue, we
      examined a lipopolysaccharide (LPS)-induced lung injury model for the role of
      activated AMphi in vivo, focusing on activation through CD40, which is one of the
      most important pathways for the activation of antigen-presenting cells. Without
      CD40, LPS-induced ALI was significantly reduced in its histological degree of
      injury and recruitment of neutrophils into the lung. In addition, the release in
      the lung of inflammatory mediators such as tumor necrosis factor-alpha,
      interleukin-1beta, macrophage inflammatory protein 2, or matrix metalloproteinase
      was significantly reduced in mice deficient in CD40 (CD40KO). To elucidate the
      mechanism of this attenuation of ALI in CD40KO mice, we studied the function of
      AMphi ex vivo. AMphi purified from CD40KO mice could not induce expression of
      inducible nitric oxide synthase (iNOS) by LPS, although iNOS in wild-type AMphi
      was induced by LPS independently of CD40-CD154 interaction. The loss of surface
      expression of CD40 was enough to interrupt the expression of iNOS in AMphi in
      response to LPS. Also based on the tissue nitrotyrosine staining, the reactive
      oxygen and nitrogen intermediates seemed to be reduced in tissue in CD40KO mice.
      These results indicated that activation of AMphi through CD40 might be involved
      not only in amplification by the interaction with CD154 but also in the
      development of ALI by CD40 itself, and that the functional blockade of CD40 would
      yield one of the targets for the treatment of LPS-induced ALI and acute
      respiratory distress syndrome.

PMID- 14693669
TI  - Imbalances in regional lung ventilation: a validation study on electrical
      impedance tomography.
AB  - Imbalances in regional lung ventilation, with gravity-dependent collapse and
      overdistention of nondependent zones, are likely associated to ventilator-induced
      lung injury. Electric impedance tomography is a new imaging technique that is
      potentially capable of monitoring those imbalances. The aim of this study was to
      validate electrical impedance tomography measurements of ventilation
      distribution, by comparison with dynamic computerized tomography in a
      heterogeneous population of critically ill patients under mechanical ventilation.
      Multiple scans with both devices were collected during slow-inflation breaths.
      Six repeated breaths were monitored by impedance tomography, showing acceptable
      reproducibility. We observed acceptable agreement between both technologies in
      detecting right-left ventilation imbalances (bias = 0% and limits of agreement = 
      10 to +10%). Relative distribution of ventilation into regions or layers
      representing one-fourth of the thoracic section could also be assessed with good
      precision. Depending on electrode positioning, impedance tomography slightly
      overestimated ventilation imbalances along gravitational axis. Ventilation was
      gravitationally dependent in all patients, with some transient blockages in
      dependent regions synchronously detected by both scanning techniques. Among
      variables derived from computerized tomography, changes in absolute air content
      best explained the integral of impedance changes inside regions of interest (r(2)
      > or = 0.92). Impedance tomography can reliably assess ventilation distribution
      during mechanical ventilation.

PMID- 14693670
TI  - Human bronchial smooth muscle cell lines show a hypertrophic phenotype typical of
      severe asthma.
AB  - We developed clonal cell lines of human bronchial smooth muscle origin by
      retroviral transduction of temperature-sensitive simian virus 40 large tumor (T)
      antigen. These cells show increased growth potential at 33 degrees C, but on
      shift to the nonpermissive temperature (39 degrees C), they show diminished or
      arrested growth. In addition to the expected reduction in the level of large T
      antigen, cells shifted to 39 degrees C show increased expression of the cyclin
      dependent kinase inhibitor p21(Waf1/Cip1), characteristic of cells arrested in G1
      of the cell cycle. Shifted cells undergo a process of cell hypertrophy, as
      demonstrated by increased time of flight and forward scatter, as well as
      increased expression of the contractile proteins alpha-smooth muscle actin,
      myosin light chain kinase, and SM22. Changes in contractile protein expression
      were regulated primarily in a posttranscriptional manner. Phosphatidylinositol 3
      kinase activity was increased in shifted cells, and chemical inhibition of
      phosphatidylinositol 3-kinase attenuated alpha-actin and myosin light-chain
      kinase expression. We have developed clonal cell lines of human bronchial smooth
      muscle origin that may be useful for the study of airway smooth muscle biology.
      Furthermore, we demonstrate that arrest of airway smooth muscle cell cycle
      traversal can induce cellular hypertrophy, which parallels changes observed in
      the airways of patients with severe asthma.

PMID- 14693671
TI  - Pulmonary function at follow-up of very preterm infants from the United Kingdom
      oscillation study.
AB  - Prematurely born infants supported by conventional ventilation (CV) frequently
      have abnormal pulmonary function when assessed in childhood. The aim of this
      study was to test the hypothesis that infants who were randomly assigned to high
      frequency oscillatory ventilation would have superior pulmonary function at
      follow-up compared with those who received CV (UK Oscillation Study). Infants
      from 12 trial centers were recruited for pulmonary function testing at a single
      center. Seventy-six infants, of a mean gestational age 26.4 weeks, were studied
      after sedation with chloral hydrate at between 11 and 14 months of age, corrected
      for prematurity. Infants assigned to CV had similar pulmonary function compared
      with those assigned to high-frequency oscillatory ventilation, with mean (SD)
      results as follows: functional residual capacity measured by whole-body
      plethysmography, 26.9 (6.3) versus 26.5 (6.4) ml/kg; functional residual capacity
      measured by helium dilution, 24.1 (5.4) versus 23.5 (5.7) ml/kg; inspiratory
      airway resistance, 3.3 (1.3) versus 3.4 (1.6) kPa. second. L; expiratory airway
      resistance, 4.4 (2.8) versus 4.1 (2.5) kPa. second. L; respiratory rate, 31.2
      (6.0) versus 33.9 (8.0) breaths/minute. We conclude that early use of high
      frequency oscillatory ventilation in very preterm infants appears to offer no
      advantage over CV in terms of pulmonary function at follow-up.

PMID- 14693672
TI  - Medium-term survival after hospitalization with community-acquired pneumonia.
AB  - An episode of community-acquired pneumonia (CAP) has been suggested to predict
      greater than expected mortality after discharge from hospital. We ascertained the
      survival status as of December 2002 of a cohort of patients with CAP identified
      prospectively between November 1998 and June 2001. Cox regression analysis was
      used to examine the impact of demographic factors, comorbid illnesses, and CAP
      severity on subsequent mortality. Of 378 CAP survivors we ascertained the
      survival status of 366 (96.9%), 125 (34.1%) of whom had died. The mean length of
      follow-up was 1,058 days (range, 602-1,500 days). Independent predictors of
      mortality were increasing age (p < 0.001), comorbid cerebrovascular (p = 0.002)
      and cardiovascular (p = 0.023) disease, an altered mental state (p < 0.001), a
      hematocrit of less than 35% (p = 0.035), and increasing blood glucose level (p =
      0.025). In 41- to 80-year-olds without significant comorbidities there was a
      trend to greater than expected mortality. In conclusion, an episode of CAP in
      young adults without significant comorbid illnesses does not appear to be an
      adverse prognostic marker of medium-term survival. The trend to greater than
      expected mortality in patients over 40 years of age needs further study and
      physicians should be particularly alert for underlying life-limiting disease
      processes in patients presenting with acute confusion or a hematocrit of less
      than 35%.

PMID- 14693675
TI  - Differential regulation of PHEX expression in bone and parathyroid gland by
      chronic renal insufficiency and 1,25-dihydroxyvitamin D3.
AB  - Mutations in the PHEX gene are responsible for X-linked hypophosphatemia, a renal
      phosphate-wasting disorder associated with defective skeletal mineralization.
      PHEX is predominantly expressed in bones and teeth and in the parathyroid gland
      of patients with chronic renal failure and tertiary hyperparathyroidism. The
      purpose of the present study was to examine the effects of renal insufficiency
      and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the regulation of PHEX expression
      in rat tibia and parathyroid gland. In rats fed a high-phosphate (Pi) diet,
      nephrectomy elicited a significant increase in the serum parathyroid hormone
      (PTH) concentration that was associated with a significant increase in the
      abundance of PHEX mRNA and protein in the tibia and a significant increase in
      PHEX mRNA in the parathyroid gland. In contrast, 1,25(OH)2D3 administration to
      intact rats fed a control diet elicited a significant decrease in the serum PTH
      concentration that was accompanied by a significant decrease in PHEX mRNA and
      protein abundance in the tibia and a significant decrease in PHEX mRNA in the
      parathyroid gland. In addition, the increases in serum PTH levels and PHEX mRNA
      in the tibia and parathyroid gland in nephrectomized rats fed a high-Pi diet were
      blunted by 1,25(OH)2D3. Serum PTH concentration was positively and significantly
      correlated with tibial PHEX mRNA and protein abundance. In summary, we
      demonstrate that PHEX expression in the tibia and parathyroid gland is increased
      by chronic renal insufficiency and decreased by 1,25(OH)2D3 administration and
      suggest that PTH status may play an important role in mediating these changes in
      PHEX expression.

PMID- 14693677
TI  - SAM68: a downstream target of angiotensin II signaling in vascular smooth muscle
      cells in genetic hypertension.
AB  - We investigated whether phosphatidylinositol 3-kinase (PI3K) and 68-kDa Src
      associated during mitosis (SAM68) are involved in angiotensin II (ANG II) growth
      signaling in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive
      rats (SHR). PI3K activity was assessed by measuring the phosphorylation of the
      regulatory subunit p85alpha and kinase activity of the catalytic 110-kDa subunit
      of PI3K. The PI3K-SAM68 interaction was assessed by coimmunoprecipitation, and
      SAM68 activity was evaluated by poly(U) binding. SAM68 expression was manipulated
      by SAM68 antisense oligonucleotide transfection. VSMC growth was evaluated by
      measuring [3H]leucine and [3H]thymidine incorporation as indexes of protein and
      DNA synthesis, respectively. ANG II increased the phosphorylation of p85alpha and
      kinase activity of the 110-kDa PI3K subunit in VSMCs from SHR and transiently
      increased p85alpha-SAM68 association. In Wistar-Kyoto (WKY) rat cells, ANG II
      increased SAM68 phosphorylation without influencing poly(U) binding. In SHR, ANG
      II did not influence SAM68 phosphorylation but increased SAM68 binding to
      poly(U). ANG II stimulated phosphoinositol phosphate synthesis by PI3K in SAM68
      immunoprecipitates in both groups, with significantly enhanced effects in SHR.
      Inhibition of PI3K, using the selective inhibitor LY-294002, and downregulation
      of SAM68, by antisense oligonucleotides, significantly decreased ANG II
      stimulated incorporation of [3H]leucine and [3H]thymidine in VSMCs, showing the
      functional significance of PI3K and SAM68. Our data demonstrate that PI3K and
      SAM68 are involved in ANG II signaling and that SAM68 is differentially regulated
      in VSMCs from SHR. These processes may contribute to the enhanced ANG II
      signaling and altered VSMC growth in SHR.

PMID- 14693678
TI  - Augmented systolic response to the calcium sensitizer EMD-57033 in a transgenic
      model with troponin I truncation.
AB  - Myocardial stunning is a form of acute reversible cardiac dysfunction that occurs
      after brief periods of ischemia and reperfusion. In several animal models,
      stunning is associated with proteolytic truncation of troponin I (TnI). Mice
      expressing the same proteolytic TnI fragment [TnI-(1-193)] demonstrate cardiac
      depression with a decreased maximal calcium-activated tension. We therefore
      hypothesized preferential improvement in mice expressing TnI-(1-193) treated with
      the calcium-sensitizing drug EMD-57033. TnI-(1-193) and nontransgenic myofibrils
      exhibited significant sensitization to calcium in Mg-ATPase assays after EMD
      57033 exposure. However, only transgenic myofibrils exhibited an increase in
      maximal activity (P = 0.023). EMD-57033 also increased maximal calcium-activated
      force in TnI-(1-193) muscle, such that it was comparable to nontransgenic cardiac
      muscle. EMD-57033 enhanced in vivo systolic function modestly in controls but had
      a marked effect in transgenic mice, with an almost threefold greater leftward
      shift of the end-systolic pressure-volume relation (P = 0.0005). These data
      indicate a targeted efficacy of EMD-57033 in offsetting the contractile defect in
      TnI-(1-193) mice, and this may have therapeutic implications in models displaying
      this myofilament defect.

PMID- 14693679
TI  - Heme oxygenase-mediated endothelial dysfunction in DOCA-salt, but not in
      spontaneously hypertensive, rat arterioles.
AB  - Vascular heme oxygenase (HO) metabolizes heme to form carbon monoxide. Carbon
      monoxide inhibits nitric oxide synthase and promotes endothelium-dependent
      vasoconstriction. We reported HO-1-mediated endothelial dysfunction in Dahl salt
      sensitive hypertension. Previous studies suggested that salt-sensitive
      hypertensive rats, but not spontaneously hypertensive rats (SHR), display
      endothelial dysfunction. This study examines the hypothesis that HO-1-mediated
      arteriolar endothelial dysfunction develops in deoxycorticosterone acetate (DOCA)
      salt hypertensive (DOCA) rats, but not in SHR. Uninephrectomized (isoflurane
      anesthesia) male Sprague-Dawley rats received DOCA injections and saline drinking
      solution for 4 wk. Rats subjected to sham surgery received vehicle injections and
      tap water. Blood pressure was elevated in DOCA rats and SHR compared with sham
      and Wistar-Kyoto (WKY) groups. Aortic HO-1 expression and blood carboxyhemoglobin
      levels were elevated in the DOCA group, but not in SHR. In isolated gracilis
      muscle arterioles, ACh caused concentration-related vasodilation in all groups,
      with attenuated maximum responses in DOCA, but not in SHR, arterioles. Acute
      pretreatment with an inhibitor of HO, chromium mesoporphyrin, restored ACh
      induced responses in DOCA arterioles to sham levels. ACh responses remained the
      same in SHR and WKY arterioles after chromium mesoporphyrin treatment. These data
      show that HO-1 levels and activity are increased and arteriolar responses to ACh
      are decreased in DOCA rats, but not in SHR. Furthermore, in DOCA arterioles, an
      inhibitor of HO restores ACh-induced vasodilation to sham levels. These results
      suggest that elevated HO-1 levels and activity, not resulting from hypertension
      per se, contribute to endothelial dysfunction in DOCA rats.

PMID- 14693680
TI  - Endogenous VEGF-A is responsible for mitogenic effects of MCP-1 on vascular
      smooth muscle cells.
AB  - Vessel wall remodeling is a complex phenomenon in which the loss of
      differentiation of vascular smooth muscle cells (VSMCs) occurs. We investigated
      the role of rat macrophage chemoattractant protein (MCP)-1 on rat VSMC
      proliferation and migration to identify the mechanism(s) involved in this kind of
      activity. Exposure to very low concentrations (1-100 pg/ml) of rat MCP-1 induced
      a significant proliferation of cultured rat VSMCs assessed as cell duplication by
      the counting of total cells after exposure to test substances. MCP-1 stimulated
      VSMC proliferation and migration in a two-dimensional lateral sheet migration of
      adherent cells in culture. Endogenous vascular endothelial growth factor-A (VEGF
      A) was responsible for the mitogenic activity of MCP-1, because neutralizing anti
      VEGF-A antibody inhibited cell proliferation in response to MCP-1. On the
      contrary, neutralizing anti-fibroblast growth factor-2 and anti-platelet-derived
      growth factor-bb antibodies did not affect VSMC proliferation induced by MCP-1.
      RT-PCR and Western blot analyses showed an increased expression of either mRNA or
      VEGF-A protein after MCP-1 activation (10-100 pg/ml), whereas no fms-like
      tyrosine kinase (Flt)-1 receptor upregulation was observed. Because we have
      previously demonstrated that hypoxia (3% O2) can enhance VSMC proliferation
      induced by VEGF-A through Flt-1 receptor upregulation, the effects of hypoxia on
      the response of VSMCs to MCP-1 were investigated. Severe hypoxia (3% O2)
      potentiated the growth-promoting effect of MCP-1, which was able to significantly
      induce cell proliferation even at a concentration as low as 0.1 pg/ml. These
      findings demonstrate that low concentrations of rat MCP-1 can directly promote
      rat VSMC proliferation and migration through the autocrine production of VEGF-A.

PMID- 14693681
TI  - Myocardial density and composition: a basis for calculating intracellular
      metabolite concentrations.
AB  - Systems for describing myocardial cellular metabolism with appropriate
      thermodynamic constraints on reactions have to be on the basis of estimates of
      intracellular and mitochondrial concentrations of metabolites as driving forces
      for reactions. This requires that tissue composition itself must be modeled, but
      there is marked inconsistency in the literature and no full data set on hearts of
      any species. To formulate a self-consistent set of information on the densities,
      contents, or concentrations of chemical components and volumes of tissue spaces,
      we drew on information mostly on rats. From the data on densities, volumes,
      volume fractions, and mass fractions observed mainly on left ventricular
      myocardium, cytoplasm, and mitochondria and from morphometric data on cellular
      components and the vasculature, we constructed a matrix based on conservation
      laws for density, volume, and constituent composition. The four constituents were
      water, protein, fat, and solutes (or ash). To take into account the variances in
      the observed data sets, we used a constrained nonlinear least squares
      optimization to minimize the differences between the final results and the data
      sets. The results provide a detailed estimate of cardiac tissue composition,
      previously unavailable, for the translation of whole tissue concentrations or
      concentrations per gram protein into estimated local concentrations that are
      relevant to reaction processes. An example is that the concentrations of
      phosphocreatine and ATP in cytosolic water space are twice as high as their mean
      tissue concentrations. This conservation optimization method is applicable to any
      tissue or organ.

PMID- 14693682
TI  - Elafin-overexpressing mice have improved cardiac function after myocardial
      infarction.
AB  - Elevated serine elastase activity after myocardial infarction can contribute to
      remodeling associated with left ventricular dilatation and dysfunction. We
      therefore assessed the effects of overexpressing the selective serine elastase
      inhibitor elafin in transgenic mice in which a myocardial infarction was caused
      by ligation of the left anterior descending coronary artery (LAD). Elevated
      serine elastase activity was observed in nontransgenic littermates as early as 6
      h after LAD ligation and persisted at 4 and 7 days but not in sham-operated or
      elafin-overexpressing transgenic mice. Myeloperoxidase activity (index of
      inflammatory cells) and matrix metalloproteinase 2 were also increased but only
      at 4 and 7 days and only in nontransgenic mice (P < 0.05 for both comparisons),
      and this increase correlated with inflammatory cell infiltration.
      Echocardiographic study at 4 days revealed indexes of diastolic dysfunction in
      nontransgenic versus elafin-overexpressing mice (P < 0.05). Morphometric and
      biochemical analyses at 28 days indicated impairment in cardiac performance, with
      greater scar thinning and infarct expansion in nontransgenic versus elafin
      transgenic littermates (P < 0.05 for all comparisons). Thus serine elastase
      inhibition appears to suppress inflammation, cardiac dilatation, and dysfunction
      after myocardial infarct.

PMID- 14693683
TI  - Nitric oxide mediates protective effect of endothelin receptor antagonism during
      myocardial ischemia and reperfusion.
AB  - Endothelin (ET) receptor antagonism protects from ischemia-reperfusion injury. We
      hypothesized that the cardioprotective effect is related to nitric oxide (NO)
      bioavailability. Buffer-perfused rat and mouse hearts were subjected to ischemia
      and reperfusion. At the onset of ischemia, the rat hearts received vehicle, the
      dual endothelin type A/type B (ETA/ETB) receptor antagonist bosentan (10 microM),
      the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 100 microM), the
      combination of bosentan and L-NMMA or the combination of bosentan, L-NMMA, and
      the NO substrate L-arginine (1 mM). Hearts from wild-type and endothelial NO
      synthase (eNOS)-deficient mice received either vehicle or bosentan. Myocardial
      performance, endothelial function, NO outflow, and eNOS expression were
      monitored. Bosentan significantly improved myocardial function during reperfusion
      in rats and in wild-type mice, but not in eNOS-deficient mice. The functional
      protection afforded by bosentan was inhibited by L-NMMA, whereas it was restored
      by L-arginine. Myocardial expression of eNOS (immunoblotting) increased
      significantly in bosentan-treated rat hearts compared with vehicle hearts.
      Recovery of NO outflow during reperfusion was enhanced in the bosentan-treated
      rat heart. The endothelium-dependent vasodilator adenosine diphosphate increased
      coronary flow by 18 +/- 9% at the end of reperfusion in the bosentan group,
      whereas it reduced coronary flow by 7 +/- 5% in the vehicle group (P < 0.001).
      The response to the endothelium-independent dilator sodium nitroprusside was not
      different between the two groups. In conclusion, the dual ETA/ETB receptor
      antagonist bosentan preserved endothelial and cardiac contractile function during
      ischemia and reperfusion via a mechanism dependent on endothelial NO production.

PMID- 14693684
TI  - Myocardial electrical alteration in canine preparations with combined chronic
      rapid pacing and progressive coronary artery occlusion.
AB  - Our objective was to create an animal preparation displaying long-term electrical
      alterations after chronic regional energetic stress without myocardial scarring.
      An Ameroid (AM) constrictor was implanted around the left circumflex coronary
      artery (LCx) 2 wk before chronic rapid ventricular pacing (CRP) was initiated at
      240 beats/min for 4 wk (CRP-AM). Comparisons were made with healthy canines and
      canines with either AM or CRP. Unipolar electrograms were recorded from 191 sites
      in the LCx territory in open-chest, anesthetized animals during sinus rhythm and
      while pacing at 120-150 beats/min, with bouts of transient rapid pacing (TRP;
      240/min). In CRP-AM and AM, ST segment elevation was identified at central sites
      and ST depression at peripheral sites, both increasing with TRP. In CRP-AM and
      CRP, the maximum negative slope of unipolar activation complexes was
      significantly depressed and activation-recovery intervals prolonged. Areas of
      inexcitability as well as irregular isocontour patterns displaying localized
      activation-recovery intervals shortening and gradients >20 ms between neighboring
      sites were identified in one-third of CRP-AM at slow rate, with increasing
      incidence and magnitude in response to TRP. In CRP-AM, programmed stimulation
      induced marked conduction delay and block as well as polymorphic ventricular
      tachycardias, which stabilized into monomorphic tachycardias with the use of
      lidocaine or procainamide. Whole cell Na(+) current and channel protein
      expression were reduced in CRP-AM and CRP. Despite complete constrictor closure,
      small areas of necrosis were detected in a minority of CRP-AM. Long-term
      electrical alterations and their exacerbation by TRP contribute to arrhythmia
      formation in collateral-dependent myocardium subjected to chronic tachycardic
      stress.

PMID- 14693685
TI  - Mitochondrial defects and heterogeneous cytochrome c release after cardiac cold
      ischemia and reperfusion.
AB  - Mitochondria play a critical role in myocardial cold ischemia-reperfusion (CIR)
      and induction of apoptosis. The nature and extent of mitochondrial defects and
      cytochrome c (Cyt c) release were determined by high-resolution respirometry in
      permeabilized myocardial fibers. CIR in a rat heart transplant model resulted in
      variable contractile performance, correlating with the decline of ADP-stimulated
      respiration. Respiration with succinate or N,N,N',N'-tetramethyl-p
      phenylenediamine dihydrochloride (substrates for complexes II and IV) was
      partially restored by added Cyt c, indicating Cyt c release. In contrast, NADH
      linked respiration (glutamate+malate) was not stimulated by Cyt c, owing to a
      specific defect of complex I. CIR but not cold ischemia alone resulted in the
      loss of NADH-linked respiratory capacity, uncoupling of oxidative phosphorylation
      and Cyt c release. Mitochondria depleted of Cyt c by controlled hypoosmotic shock
      provided a kinetic model of homogeneous Cyt c depletion. Comparison to Cyt c
      control of respiration in CIR-injured myocardial fibers indicated heterogeneity
      of Cyt c release. The complex I defect and uncoupling correlated with
      heterogeneous Cyt c release, the extent of which increased with loss of cardiac
      performance. These results demonstrate a complex pattern of multiple
      mitochondrial damage as determinants of CIR injury of the heart.

PMID- 14693686
TI  - A rapidly activating delayed rectifier K+ current regulates pacemaker activity in
      adult mouse sinoatrial node cells.
AB  - We have investigated the physiological role of the "rapidly activating" delayed
      rectifier K+ current (IKr) in pacemaker activity in isolated sinoatrial node
      (SAN) myocytes and the expression of mouse ether-a-go-go (mERG) genes in the
      adult mouse SAN. In isolated, voltage-clamped SAN cells, outward currents evoked
      by depolarizing steps (greater than -40 mV) were strongly inhibited by the class
      III methanesulfonanilide compound E-4031 (1-2.5 microM), and the deactivation
      "tail" currents that occurred during repolarization to a membrane potential of 
      45 mV were completely blocked. E-4031-sensitive currents (IKr) reached a maximum
      at a membrane potential of -10 mV and showed pronounced inward rectification at
      more-positive membrane potentials. Activation of IKr occurred at -40 to 0 mV,
      with half-activation at about -24 mV. The contribution of IKr to action potential
      repolarization and diastolic depolarization was estimated by determining the E
      4031-sensitive current evoked during voltage clamp with a simulated mouse SAN
      action potential. IKr reached its peak value (approximately 0.6 pA/pF) near -25
      mV, close to the midpoint of the repolarization phase of the simulated action
      potential, and deactivated almost completely during the diastolic interval. E
      4031 (1 microM) slowed the spontaneous pacing rate of Langendorff-perfused,
      isolated adult mouse hearts by an average of 36.5% (n = 5). Expression of mRNA
      corresponding to three isoforms coded by the mouse ERG1 gene (mERG1), mERG1a,
      mERG1a', and mERG1b, was consistently found in the SAN. Our data provide the
      first detailed characterization of IKr in adult mouse SAN cells, demonstrate that
      this current plays an important role in pacemaker activity, and indicate that
      multiple isoforms of mERG1 can contribute to native SAN IKr.

PMID- 14693687
TI  - Increases in brain and cardiac AT1 receptor and ACE densities after myocardial
      infarct in rats.
AB  - In the brain, ouabain-like compounds (OLC) and the reninangiotensin system (RAS)
      contribute to sympathetic hyperactivity in rats after myocardial infarction (MI).
      This study aimed to evaluate changes in components of the central vs. the
      peripheral RAS. Angiotensin-converting enzyme (ACE) and angiotensin type 1 (AT1)
      receptor binding densities were determined by measuring 125I-labeled 351A and
      125I-labeled ANG II binding 4 and 8 wk after MI. In the brain, ACE and AT1
      receptor binding increased 8-15% in the subfornical organ, 14-22% in the organum
      vasculosum laminae terminalis, 20-34% in the paraventricular nucleus, and 13-15%
      in the median preoptic nucleus. In the heart, the greatest increase in ACE and
      AT1 receptor binding occurred at the infarct scar (approximately 10-fold) and the
      least in the right ventricle (2-fold). In kidneys, ACE and AT1 receptor binding
      decreased 10-15%. After intracerebroventricular infusion of Fab fragments to
      block brain OLC from 0.5 to 4 wk after MI, increases in ACE and AT1 receptors in
      the subfornical organ, organum vasculosum laminae terminalis, paraventricular
      nucleus, and medial preoptic nucleus were markedly inhibited, and ACE and AT1
      receptor densities in the heart increased less (6-fold in the infarct scar). In
      kidneys, decreases in ACE and AT1 receptor binding were absent after treatment
      with Fab fragments. These results demonstrate that ACE and AT1 receptor binding
      densities increase not only in the heart but also in relevant areas of the brain
      of rats after MI. Brain OLC appears to play a major role in activation of brain
      RAS in rats after MI and, to a modest degree, in activation of the cardiac RAS.

PMID- 14693688
TI  - Action potential modulation of connexin40 gap junctional conductance.
AB  - Connexin40 (Cx40) is abundantly expressed in the atrial myocardium, ventricular
      conduction system, and vascular endothelial and smooth muscle cells of the
      mammalian cardiovascular system. Rapid conduction through cardiac tissues depends
      on electrotonic transfer of the action potential between neighboring cells. To
      determine whether transjunctional voltages (Vj) elicited by an action potential
      can modulate conductance of Cx40 gap junctions, simulated myocardial action
      potentials were applied as voltage-clamp waveforms to Cx40 gap junctions
      expressed in mouse neuro2A (N2A) cells. Junctional currents resembled the action
      potential morphology but declined by >50% from peak to near-constant plateau
      values. Kinetics of Cx40 voltage gating were examined at peak voltages > or =100
      mV, and decay time constants changed e-fold per 17.6 mV for Vj > +/-40 mV.
      Junctional conductance recovered during phase 3 repolarization and early diastole
      to initial values. These phasic changes in junctional conductance were due to
      rapid decay kinetics, increasing to tens of milliseconds at peak Vj of 130 mV,
      and the increase in the steady-state conductance curve as Vj returned toward 0
      mV. Time-dependent conductance curves for Cx40 were modeled with one inactivation
      and two recovery Vj-dependent components. There was a temporal correlation
      between development of conduction delay or block and the inactivation phase of
      junctional conductance. Likewise, recovery of junctional conductance was
      coincident with recovery from refractoriness, suggesting that gap junctions may
      play a role in the genesis and propagation of cardiac arrhythmias.

PMID- 14693689
TI  - HMG-CoA reductase inhibitor attenuates platelet adhesion in intestinal venules of
      hypercholesterolemic mice.
AB  - Whereas the anti-inflammatory properties of statins have been extensively
      studied, less attention has been devoted to the antithrombogenic effects of these
      drugs. We evaluated the effect of short-term (18 h) treatment with pravastatin (1
      mg/kg) on hypercholesterolemia-induced platelet-endothelial (P/E) cell adhesion
      in intestinal venules. Mice were placed on either a normal diet (ND) or
      cholesterol-enriched diet (HCD) for 2 wk. Wild-type mice fed a HCD exhibited
      significantly elevated blood serum cholesterol levels, which were unaltered by
      pravastatin treatment. ND or HCD platelets were isolated, fluorescently labeled,
      and administered to either ND or HCD recipients. Intravital videomicroscopy was
      used to quantify transient (saltation) and firm adhesion of platelets. HCD mice
      receiving platelets from either ND or HCD mice exhibited increased P/E cell
      interactions compared with ND mice receiving platelets from ND or HCD mice. P/E
      adhesion was dramatically reduced when platelets from donor mice, recipient mice,
      or both were treated with pravastatin. The protective effect of pravastatin in
      hypercholesterolemia-induced P/E cell adhesion was abolished in N(G)-nitro-l
      arginine methyl ester-treated mice. These results indicate that 1).
      hypercholesterolemia-induced P/E cell adhesion is mediated by changes in the
      vascular wall rather than circulating platelets; 2). pravastatin treatment
      inhibits the prothrombogenic effects of hypercholesterolemia via an action on
      both endothelial cells and platelets; and 3). the protective effect of
      pravastatin is nitric oxide dependent.

PMID- 14693690
TI  - Transmission of maternal islet antibodies and risk of autoimmune diabetes in
      offspring of mothers with type 1 diabetes.
AB  - It is suggested that the maternal transmission of islet autoantibodies increases
      the risk of autoimmune diabetes in mice. The aim of this study was to determine
      whether fetal exposure to islet autoantibodies modified the risk of type 1
      diabetes in humans. Islet autoantibodies were measured at birth in 720 offspring
      of mothers with type 1 diabetes. Offspring were prospectively followed for the
      development of multiple islet autoantibodies and diabetes. Offspring who were GAD
      or IA-2 autoantibody positive at birth (n = 678) had significantly lower risks
      for developing multiple islet autoantibodies (5-year risk 1.3%) and diabetes (8
      year risk 1.1%) than offspring who were islet autoantibody negative at birth
      (5.3%, P = 0.008; and 3%, P = 0.04, respectively). Risk remained reduced after
      adjustment for birth weight, gestational age, or maternal diabetes duration
      (adjusted hazards ratio 0.25, P = 0.007 for multiple islet autoantibodies; 0.25,
      P = 0.04 for diabetes). Protection in offspring with islet autoantibodies at
      birth was most striking in offspring without the HLA DRB1*03/DRB1*04-DQB1*0302
      genotype. Maternal transmission of antibodies to exogenous insulin did not affect
      diabetes risk in offspring. These findings suggest that fetal exposure to islet
      autoantibodies in children born to mothers with type 1 diabetes may be protective
      against future islet autoimmunity and diabetes.

PMID- 14693691
TI  - Epac: A new cAMP-binding protein in support of glucagon-like peptide-1 receptor
      mediated signal transduction in the pancreatic beta-cell.
AB  - Recently published studies of islet cell function reveal unexpected features of
      glucagon-like peptide-1 (GLP-1) receptor-mediated signal transduction in the
      pancreatic beta-cell. Although GLP-1 is established to be a cAMP-elevating agent,
      these studies demonstrate that protein kinase A (PKA) is not the only cAMP
      binding protein by which GLP-1 acts. Instead, an alternative cAMP signaling
      mechanism has been described, one in which GLP-1 activates cAMP-binding proteins
      designated as cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs, also
      known as Epac). Two variants of Epac (Epac1 and Epac2) are expressed in beta
      cells, and downregulation of Epac function diminishes stimulatory effects of GLP
      1 on beta-cell Ca(2+) signaling and insulin secretion. Of particular note are new
      reports demonstrating that Epac couples beta-cell cAMP production to the
      stimulation of fast Ca(2+)-dependent exocytosis. It is also reported that Epac
      mediates the cAMP-dependent mobilization of Ca(2+) from intracellular Ca(2+)
      stores. This is a process of Ca(2+)-induced Ca(2+) release (CICR), and it
      generates an increase of [Ca(2+)](i) that may serve as a direct stimulus for
      mitochondrial ATP production and secretory granule exocytosis. This article
      summarizes new findings concerning GLP-1 receptor-mediated signal transduction
      and seeks to define the relative importance of Epac and PKA to beta-cell stimulus
      secretion coupling.

PMID- 14693692
TI  - Portal serotonin infusion and glucose disposal in conscious dogs.
AB  - Whether serotonin (5-hydroxytryptamine [5-HT]) enhances net hepatic glucose
      uptake (NHGU) during glucose infusion was examined in conscious 42-h-fasted dogs,
      using arteriovenous difference and tracer ([3-(3)H]glucose) techniques.
      Experiments consisted of equilibration (-120 to -30 min), basal (-30 to 0 min),
      and experimental (0-390 min) periods. During the experimental period,
      somatostatin, fourfold basal intraportal insulin, basal intraportal glucagon, and
      peripheral glucose (to double the hepatic glucose load) were infused. In one
      group of dogs (SER; n = 8), saline was infused intraportally from 0 to 90 min
      (P1), and 5-HT was infused intraportally at 10, 20, and 40 microg.kg(-1).min(-1)
      from 90 to 150 (P2), 150 to 210 (P3), and 210 to 270 (P4) min, respectively. In
      the other group (SAL; n = 8), saline was infused intraportally from 0 to 270 min.
      NHGU in SAL was 12.4 +/- 2.3, 14.9 +/- 2.7, 13.4 +/- 2.1, and 15.1 +/- 1.8
      micromol.kg(-1).min(-1) in P1 to P4, respectively, whereas NHGU in SER averaged
      13.2 +/- 3.0, 16.4 +/- 2.4, 19.0 +/- 2.4 (P < 0.05 vs. SAL), and 22.0 +/- 2.9
      micromol.kg(-1).min(-1) (P < 0.05 vs. SAL). Nonhepatic glucose uptake (
      micromol.kg(-1).min(-1)) in SAL was 31.7 +/- 4.9, 43.9 +/- 5.1, 55.1 +/- 5.6, and
      66.2 +/- 8.6 during P1 to P4, respectively, whereas in SER, the corresponding
      values were 26.1 +/- 5.7, 31.6 +/- 9.4, 35.1 +/- 7.6 (P < 0.05 vs. SAL), and 34.7
      +/- 7.7 (P < 0.05 vs. SAL). Intraportal 5-HT enhances NHGU but blunts nonhepatic
      glucose uptake, raising the possibility that hepatic-targeted 5-HT or 5-HT
      receptor agonists might reduce postprandial hyperglycemia.

PMID- 14693693
TI  - Exercise-induced protein kinase C isoform-specific activation in human skeletal
      muscle.
AB  - We determined whether protein kinase C (PKC) isoforms are redistributed and
      phosphorylated in response to acute exercise in skeletal muscle. Muscle biopsies
      were obtained from six healthy subjects (four women, two men; age 25 +/- 1 years)
      before, during, and after 60 min of one-leg cycle ergometry at approximately 70%
      VO(2peak). Exercise for 30 and 60 min was associated with a three- and fourfold
      increase in PKC-zeta/lambda abundance and a four- and threefold increase in
      phosphorylation, respectively, in total membranes (P < 0.05) and a decrease in
      PKC-zeta/lambda phosphorylation in cytosolic fractions. During exercise recovery,
      PKC-zeta/lambda abundance and phosphorylation remained elevated. PKC-zeta/lambda
      abundance and phosphorylation were increased in nonexercised muscle upon
      cessation of exercise, indicating a systemic response may contribute to changes
      in PKC abundance and phosphorylation. Exercise did not change PKC-delta or 
      epsilon abundance or phosphorylation in either the cytosolic or total membrane
      fraction. In conclusion, exercise is associated with an isoform-specific effect
      on PKC. PKC-zeta/lambda are candidate PKC isoforms that may play a role in the
      regulation of exercise-related changes in metabolic and gene-regulatory
      responses.

PMID- 14693694
TI  - Ceramide content is increased in skeletal muscle from obese insulin-resistant
      humans.
AB  - Increased intramyocellular lipid concentrations are thought to play a role in
      insulin resistance, but the precise nature of the lipid species that produce
      insulin resistance in human muscle are unknown. Ceramides, either generated via
      activation of sphingomyelinase or produced by de novo synthesis, induce insulin
      resistance in cultured cells by inhibitory effects on insulin signaling. The
      present study was undertaken to determine whether ceramides or other
      sphingolipids are increased in muscle from obese insulin-resistant subjects and
      to assess whether ceramide plays a role in the insulin resistance of Akt in human
      muscle. Lean insulin-sensitive and obese insulin-resistant subjects (n = 10 each)
      received euglycemic-hyperinsulinemic clamps with muscle biopsies basally and
      after 30, 45, or 60 min of insulin infusion. The rate of glucose infusion
      required to maintain euglycemia (reflecting glucose uptake) was reduced by >50%,
      as expected, in the obese subjects at each time point (P < 0.01). Under basal
      conditions, total muscle ceramide content was increased nearly twofold in the
      obese subjects (46 +/- 9 vs. 25 +/- 2 pmol/2 mg muscle, P < 0.05). All species of
      ceramides were increased similarly in the obese subjects; in contrast, no other
      sphingolipid was increased. Stimulation of Akt phosphorylation by insulin in the
      obese subjects was significantly reduced after 30 min (0.96 +/- 0.11 vs. 1.84 +/-
      0.38 arbitrary units) or 45-60 min (0.68 +/- 0.17 vs. 1.52 +/- 0.26) of insulin
      infusion (P < 0.05 for both). Muscle ceramide content was significantly
      correlated with the plasma free fatty acid concentration (r = 0.51, P < 0.05). We
      conclude that obesity is associated with increased intramyocellular ceramide
      content. This twofold increase in ceramide may be involved in the decrease in Akt
      phosphorylation observed after insulin infusion and could theoretically play a
      role in the reduced ability of insulin to stimulate glucose uptake in skeletal
      muscle from obese subjects.

PMID- 14693695
TI  - Nonesterified fatty acids and hepatic glucose metabolism in the conscious dog.
AB  - We used tracer and arteriovenous difference techniques in conscious dogs to
      determine the effect of nonesterified fatty acids (NEFAs) on net hepatic glucose
      uptake (NHGU). The protocol included equilibration ([3-(3)H]glucose), basal, and
      two experimental periods (-120 to -30, -30 to 0, 0-120 [period 1], and 120-240
      min [period 2], respectively). During periods 1 and 2, somatostatin, basal
      intraportal insulin and glucagon, portal glucose (21.3 micromol.kg(-1).min(-1)),
      peripheral glucose (to double the hepatic glucose load), and peripheral nicotinic
      acid (1.5 mg.kg(-1).min(-1)) were infused. During period 2, saline (nicotinic
      acid [NA], n = 7), lipid emulsion (NA plus lipid emulsion [NAL], n = 8), or
      glycerol (NA plus glycerol [NAG], n = 3) was infused peripherally. During period
      2, the NA and NAL groups differed (P < 0.05) in rates of NHGU (10.5 +/- 2.08 and
      4.7 +/- 1.9 micromol.g(-1).min(-1)), respectively, endogenous glucose R(a) (2.3
      +/- 1.4 and 10.6 +/- 1.0 micromol.kg(-1).min(-1)), net hepatic NEFA uptakes (0.1
      +/- 0.1 and 1.8 +/- 0.2 micromol.kg(-1).min(-1)), net hepatic beta
      hydroxybutyrate output (0.1 +/- 0.0 and 0.4 +/- 0.1 micromol.kg(-1).min(-1)), and
      net hepatic lactate output (6.5 +/- 1.7 vs. -2.3 +/- 1.2 micromol.kg(-1).min(
      1)). Hepatic glucose uptake and release were 2.6 micro mol. kg(-1). min(-1) less
      and 3.5 micro mol. kg(-1). min(-1) greater, respectively, in the NAL than NA
      group (NS). The NAG group did not differ significantly from the NA group in any
      of the parameters listed above. In the presence of hyperglycemia and relative
      insulin deficiency, elevated NEFAs reduce NHGU by stimulating hepatic glucose
      release and suppressing hepatic glucose uptake.

PMID- 14693696
TI  - Dehydroepiandrosterone stimulates glucose uptake in human and murine adipocytes
      by inducing GLUT1 and GLUT4 translocation to the plasma membrane.
AB  - Dehydroepiandrosterone (DHEA) has been shown to modulate glucose utilization in
      humans and animals, but the mechanisms of DHEA action have not been clarified. We
      show that DHEA induces a dose- and time-dependent increase in glucose transport
      rates in both 3T3-L1 and human adipocytes with maximal effects at 2 h. Exposure
      of adipocytes to DHEA does not result in changes of total GLUT4 and GLUT1 protein
      levels. However, it does result in significant increases of these glucose
      transporters in the plasma membrane. In 3T3-L1 adipocytes, DHEA increases
      tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 and
      stimulates IRS-1- and IRS-2-associated phosphatidylinositol (PI) 3-kinase
      activity with no effects on either insulin receptor or Akt phosphorylation. In
      addition, DHEA causes significant increases of cytosolic Ca(2+) concentrations
      and a parallel activation of protein kinase C (PKC)-beta(2). The effects of DHEA
      are abrogated by pretreatment of adipocytes with PI 3-kinase and phospholipase C
      gamma inhibitors, as well as by inhibitors of Ca(2+)-dependent PKC isoforms,
      including a specific PKC-beta inhibitor. Thus, DHEA increases glucose uptake in
      both human and 3T3-L1 adipocytes by stimulating GLUT4 and GLUT1 translocation to
      the plasma membrane. PI 3-kinase, phospholipase C gamma, and the conventional PKC
      beta(2) seem to be involved in DHEA effects.

PMID- 14693697
TI  - PKC alpha is activated but not required during glucose-induced insulin secretion
      from rat pancreatic islets.
AB  - The role of protein kinase C (PKC) in glucose-stimulated insulin secretion (GSIS)
      is controversial. Using recombinant adenoviruses for overexpression of PKC alpha
      and PKC delta, in both wild-type (WT) and kinase-dead (KD) forms, we here
      demonstrate that activation of these two PKCs is neither necessary nor sufficient
      for GSIS from batch-incubated, rat pancreatic islets. In contrast, responses to
      the pharmacologic activator 12-O-tetradecanoylphorbol-13-acetate (TPA) were
      reciprocally modulated by overexpression of the PKC alpha WT or PKC alpha KD but
      not the corresponding PKC delta adenoviruses. The kinetics of the secretory
      response to glucose (monitored by perifusion) were not altered in either cultured
      islets overexpressing PKC alpha KD or freshly isolated islets stimulated in the
      presence of the conventional PKC (cPKC) inhibitor Go6976. However, the latter did
      inhibit the secretory response to TPA. Using phosphorylation state-specific
      antisera for consensus PKC phosphorylation sites, we also showed that (compared
      with TPA) glucose causes only a modest and transient functional activation of PKC
      (maximal at 2-5 min). However, glucose did promote a prolonged (15 min)
      phosphorylation of PKC substrates in the presence of the phosphatase inhibitor
      okadaic acid. Overall, the results demonstrate that glucose does stimulate PKC
      alpha in pancreatic islets but that this makes little overall contribution to
      GSIS.

PMID- 14693698
TI  - Islet-sparing effects of protein tyrosine phosphatase-1b deficiency delays onset
      of diabetes in IRS2 knockout mice.
AB  - Protein tyrosine phosphatase-1b (Ptp1b) inhibits insulin and leptin signaling by
      dephosphorylating specific tyrosine residues in their activated receptor
      complexes. Insulin signals are mediated by tyrosine phosphorylation of the
      insulin receptor and its downstream targets, such as Irs1 and Irs2. Irs2 plays an
      especially important role in glucose homeostasis because it mediates some
      peripheral actions of insulin and promotes pancreatic beta-cell function. To
      determine whether the deletion of Ptp1b compensates for the absence of Irs2, we
      analyzed mice deficient in both Ptp1b and Irs2. Pancreatic beta-cell area
      decreased in Ptp1b(-/-) mice, consistent with decreased insulin requirements
      owing to increased peripheral insulin sensitivity. By contrast, peripheral
      insulin sensitivity and beta-cell area increased in Irs2(-/-)::Ptp1b(-/-) mice,
      which improved glucose tolerance in Irs2(-/-)::Ptp1b(-/-) mice and delayed
      diabetes until 3 months of age. However, beta-cell function eventually failed to
      compensate for absence of Irs2. Our studies demonstrate a novel role for Ptp1b in
      regulating beta-cell homeostasis and indicate that Ptp1b deficiency can partially
      compensate for lack of Irs2.

PMID- 14693699
TI  - Metabolic pathways that mediate inhibition of hypothalamic neurons by glucose.
AB  - Neurons in the ventromedial hypothalamus mediate some counterregulatory responses
      to hypoglycemia and 2-deoxyglucose, but the mechanisms that mediate these
      responses to glucose are unclear. In the present study, ventromedial hypothalamus
      neurons were identified on the basis of their inhibition by the transition from 5
      to 20 mmol/l glucose. Tolbutamide, which activates glucose-stimulated neurons,
      failed to inhibit or activate glucose-inhibited neurons. Inhibitors of glucose
      transport and glycolysis, in particular by the glucokinase inhibitor glucosamine,
      blocked the effect of glucose on glucose-inhibited neurons. Furthermore, the
      glucose-inhibited neurons were activated by 2-deoxyglucose, which also activates
      counterregulatory responses. Conversely, glucose-inhibited neurons were inhibited
      by glycolytic metabolites, including lactate, but not by pyruvate. These data
      indicate that hypoglycemia induces electrical activity in glucose-inhibited
      neurons by attenuating glycolysis in those neurons. Thus, counterregulatory
      failure could be due to relatively enhanced glycolysis in glucose-stimulated
      neurons during hypoglycemia and attenuation of glycolysis in glucose-inhibited
      neurons might reverse counterregulatory failure.

PMID- 14693700
TI  - Stimulation of lipolysis by tumor necrosis factor-alpha in 3T3-L1 adipocytes is
      glucose dependent: implications for long-term regulation of lipolysis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) and hyperglycemia both impair insulin
      sensitivity in vivo. This may be secondary to stimulation of adipose tissue
      lipolysis and consequent increased circulating free fatty acids (FFAs). Here we
      report that neither TNF-alpha nor glucose alone has a pronounced effect on
      lipolysis in 3T3-L1 adipocytes. However, the combination of TNF-alpha plus
      glucose markedly stimulates lipolysis. Glucose does not affect the ability of
      isoproterenol to stimulate lipolysis. Alternative substrates such as acetate,
      pyruvate, and lactate do not allow the TNF-alpha effect. Mannose was almost as
      effective as glucose; fructose was marginally effective, but galactose was
      ineffective. The effectiveness of the sugars corresponded with production of
      lactate, i.e., the cells readily produced lactate from glucose or mannose,
      slightly from fructose, and not at all from galactose. The ability of TNF-alpha
      to phosphorylate extracellular signal-regulated kinase 1 (ERK1) and ERK2 and to
      downregulate perilipin (which has been implicated in the lipolytic effect of TNF
      alpha) was not affected by glucose. We conclude that the lipolytic action of TNF
      alpha is influenced by glucose in 3T3-L1 adipocytes. The findings suggest that
      glucose metabolism is required for the lipolytic response to TNF-alpha but not
      for early signaling events. These findings suggest novel mechanisms by which TNF
      alpha and hyperglycemia raise FFA levels and induce insulin resistance.

PMID- 14693701
TI  - Responsiveness to peripherally administered melanocortins in lean and obese mice.
AB  - To elucidate mechanisms of melanocortin action, we investigated the effects of a
      melanocortin receptor agonist (melanotetan II [MTII]) in lean C57BL/6J and obese
      (DIO, ob/ob, UCP1-DTA) mice. MTII administration (100 microg q.i.d. i.p.) for 24
      h results in similar weight loss but a more pronounced decrease of food intake in
      DIO mice. After 4 and 8 days of MTII treatment, however, the reduction in both
      food intake and body weight is more pronounced in DIO mice than in lean mice.
      MTII administration for 24 h prevents food deprivation-induced alterations in
      hypothalamic neuropeptide Y (NPY) and liver adiponectin receptor 1 and
      adiponectin receptor 2 mRNA expression, but does not alter hypothalamic mRNA
      expression of melanocortin 4 receptor or adiponectin serum and mRNA expression
      levels. NPY and agouti gene-related protein (AgRP) mRNA expression after 8 days
      of MTII is increased to levels comparable to pair-fed mice. In summary, 1) MTII
      is an effective treatment for obesity and related metabolic defects in leptin
      resistant (DIO, UCP1-DTA) and leptin-sensitive (ob/ob) mouse models of obesity;
      2) the effects of MTII on food intake and body weight are more pronounced in DIO
      mice than in lean mice; 3) the tachyphylactic effect after prolonged MTII
      administration appears to be, at least in part, caused by a compensatory
      upregulation of NPY and AgRP mRNA levels, whereas decreasing leptin levels may
      play a very minor role in mediating tachyphylaxis; and 4) alterations in
      adiponectin receptor mRNA expression after fasting or MTII treatment may
      contribute to altered insulin sensitivity and needs to be studied further.

PMID- 14693702
TI  - Recruitment of bone marrow-derived endothelial cells to sites of pancreatic beta
      cell injury.
AB  - Endothelial progenitor cells (EPCs) are detectable in the blood and bone marrow
      throughout life. These cells contribute to new blood vessel formation
      (neovascularization) in physiological states such as wound healing and in
      pathological states such as tumor angiogenesis. We hypothesized that bone marrow
      derived EPCs could play a role in the response to pancreatic islet cell injury.
      We used a murine model of experimentally induced beta-cell injury followed by
      transplantation with genetically marked bone marrow cells. Bone marrow-derived
      cells were detectable throughout the pancreas after transplantation. Whereas the
      total number of bone marrow-derived cells in the pancreas decreased over time,
      the frequency of endothelial cells (of both donor and recipient origin) increased
      after transplantation in the animals in which beta-cell injury had been induced.
      There was no evidence in this model that bone marrow-derived cells differentiated
      into insulin-expressing cells. This study provides evidence that bone marrow
      derived EPCs are recruited to the pancreas in response to islet injury. EPC
      mediated neovascularization of the pancreas could in principle be exploited to
      facilitate the recovery of non-terminally injured beta-cells or to improve the
      survival and/or function of islet allografts.

PMID- 14693703
TI  - Caspase-1 is not required for type 1 diabetes in the NOD mouse.
AB  - Interleukin (IL)-1 beta and IL-18 are two cytokines associated with the
      immunopathogenesis of diabetes in NOD mice. Both of these cytokines are cleaved
      by caspase-1 to their biologically active forms. IL-1 is a proinflammatory
      cytokine linked to beta-cell damage, and IL-18 stimulates production of
      interferon (IFN)gamma in synergy with IL-12. To examine the effects produced by
      caspase-1 deficiency on diabetes development in NOD/Lt mice, a disrupted Casp1
      gene was introduced by a speed congenic technique. Casp1(-/-) bone marrow-derived
      macrophages stimulated with lipopolysaccharide produced no detectable IL-18,
      fourfold lower IL-1 beta, and 20-30% less IL-1 alpha than macrophages from wild
      type Casp1(+/+) or Casp1(+/-) controls. Unexpectedly, despite reduced IL-1 and IL
      18, there was no change in the rate of diabetes or in total incidence as compared
      with that in wild-type NOD mice. IL-1 reportedly makes an important pathological
      contribution in the multidose streptozotocin model of diabetes; however, there
      was no difference in sensitivity to streptozotocin between NOD mice and
      NOD.Casp1(-/-) mice at 40 mg/kg body wt or at 25 mg/kg body wt dosage levels.
      These findings show that caspase-1 processing of IL-1 beta and IL-18 is not
      absolutely required for mediation of spontaneous or chemically induced diabetes
      pathogenesis in the NOD mouse.

PMID- 14693704
TI  - Transplantation of reversibly immortalized insulin-secreting human hepatocytes
      controls diabetes in pancreatectomized pigs.
AB  - Type 1 diabetes results from the destruction of insulin-producing pancreatic beta
      cells by a beta-cell-specific autoimmune process. Although converting other cell
      types into insulin-producing cells may compensate for the loss of the beta-cell
      mass while evading beta-cell-specific T-cell responses, proof-of-principle of
      this approach in large animal models is lacking. This investigation was initiated
      to determine whether an insulin-producing human hepatocyte line can control
      diabetes when transplanted into totally pancreatectomized diabetic pigs. We
      established a reversibly immortalized human hepatocyte line, YOCK-13, by
      transferring a human telomerase reverse transcriptase cDNA and a drug-inducible
      Cre recombinase cassette, followed by cDNA for a modified insulin under the
      control of the L-type pyruvate kinase (L-PK) promoter. YOCK-13 cells produced
      small amounts of modified insulin and no detectable endogenous L-PK at low
      glucose concentrations, whereas they produced large amounts of both modified
      insulin and L-PK in response to high glucose concentrations. Xenotransplantation
      of YOCK-13 cells via the portal vein into immunosuppressed, totally
      pancreatectomized pigs decreased hyperglycemia and prolonged survival without
      adverse effects such as portal thrombosis, liver necrosis, pulmonary embolism,
      and tumor development. We suggest that this reversibly immortalized, insulin
      secreting human hepatocyte line may overcome the shortage of donor pancreata for
      islet transplantation into patients with type 1 diabetes.

PMID- 14693705
TI  - IL-1 receptor deficiency slows progression to diabetes in the NOD mouse.
AB  - Proinflammatory cytokines are believed to be important in pancreatic beta-cell
      destruction in the development of type 1 diabetes. They act by upregulation of
      genes including Fas and inducible nitric oxide synthase (iNOS), which have both
      been shown to lead to beta-cell death in vitro. We used mice deficient in the
      interleukin (IL)-1 receptor (IL-1R) to assess the contribution of IL-1 to
      different models of diabetes. IL-1R-deficient islets were protected from the
      damaging effects of tumor necrosis factor (TNF) and interferon (IFN)-gamma in
      vitro, and beta-cell expression of iNOS was reduced, suggesting that IL-1
      mediates the induction of iNOS by TNF and IFN-gamma. IL-1 action was not required
      for induction of class I major histocompatibility complex or Fas by TNF and IFN
      gamma. IL-1R-deficient nonobese diabetic (NOD) mice developed diabetes
      significantly slower than wild-type mice. IL-1R deficiency did not affect
      diabetes in 8.3 TCR transgenic NOD mice but prolonged the time to diabetes in
      BDC2.5 TCR transgenic NOD mice. We conclude that IL-1R deficiency slows
      progression to diabetes in NOD mice but on its own does not prevent diabetes.

PMID- 14693706
TI  - Inhibition of lipase activity and lipolysis in rat islets reduces insulin
      secretion.
AB  - Lipids may serve as coupling factors in K(ATP)-independent glucose sensing in
      beta-cells. We have previously demonstrated that beta-cells harbor lipase
      activities, one of which is the hormone-sensitive lipase. Whether beta-cell
      lipases are critical for glucose-stimulated insulin secretion (GSIS) by providing
      lipid-derived signals from endogenous lipids is unknown. Therefore, using a
      lipase inhibitor (orlistat), we examined whether lipase inhibition reduces
      insulin secretion. Islet lipolysis stimulated by glucose and diglyceride lipase
      activity was abolished by orlistat. Incubation of rat islets with orlistat dose
      dependently inhibited GSIS; this inhibition was reversed by 1 mmol/l palmitate,
      suggesting that orlistat acts via impaired formation of an acylglyceride-derived
      coupling signal. Orlistat inhibited the potentiating effect of forskolin on GSIS,
      an effect proposed to be due to activation of a lipase. In perifused islets,
      orlistat attenuated mainly the second phase of insulin secretion. Because the
      rise in islet ATP/ADP levels in response to glucose and oxidation of the sugar
      were unaffected by orlistat whereas the second phase of insulin secretion was
      reduced, it seems likely that a lipid coupling factor involved in K(ATP)
      independent glucose sensing has been perturbed. Thus, beta-cell lipase activity
      is involved in GSIS, emphasizing the important role of beta-cell lipid metabolism
      for insulin secretion.

PMID- 14693707
TI  - Gene and protein kinase expression profiling of reactive oxygen species
      associated lipotoxicity in the pancreatic beta-cell line MIN6.
AB  - Oligonucleotide microarrays were used to define oleic acid (OA)-regulated gene
      expression and proteomic technology to screen protein kinases in MIN6 insulinoma
      cells. The effects of oxidative stress caused by OA and potential protective
      effects of N-acetyl-L-cysteine (NAC), a scavenger of reactive oxygen species
      (ROS), on global gene expression and beta-cell function were investigated. Long
      term exposure of MIN6 cells to OA led to a threefold increase in basal insulin
      secretion, a 50% decrease in insulin content, an inhibition of glucose-stimulated
      insulin secretion (GSIS), and a twofold increase in the level of ROS. The
      addition of NAC normalized both the OA-induced insulin content and ROS elevation,
      but it failed to restore GSIS. Microarray studies and subsequent quantitative PCR
      analysis showed that OA consistently regulated the expression of 45 genes
      involved in metabolism, cell growth, signal transduction, transcription, and
      protein processing. The addition of NAC largely normalized the expression of the
      OA-regulated genes involved in cell growth and differentiation but not other
      functions. A protein kinase screen showed that OA regulated the expression and/or
      phosphorylation levels of kinases involved in stress-response mitogen-activated
      protein kinase, phosphatidylinositol 3-kinase, and cell cycle control pathways.
      Importantly, these findings indicate that chronic OA exposure can impair beta
      cell function through ROS-dependent and -independent mechanisms.

PMID- 14693708
TI  - Role of beta-cell prohormone convertase (PC)1/3 in processing of pro-islet
      amyloid polypeptide.
AB  - Islet amyloid polypeptide (IAPP) (amylin), the major component of islet amyloid,
      is produced by cleavage at the COOH- and NH(2)-termini of its precursor, proIAPP,
      likely by the beta-cell prohormone convertases (PC) 1/3 and PC2. Mice lacking PC2
      can process proIAPP at its COOH- but not its NH(2)-terminal cleavage site,
      suggesting that PC1/3 is capable of initiating proIAPP cleavage at its COOH
      terminus. To determine the precise role of PC1/3 in proIAPP processing, Western
      blot analysis was performed on islets isolated from mice lacking PC1/3 (PC1/3(-/
      )). These islets contained not only fully processed IAPP as in PC1/3(+/+) islets,
      but also elevated levels of a COOH-terminally unprocessed intermediate form,
      suggesting impaired processing at the COOH-terminus. Next, GH3 cells that do not
      normally express proIAPP or detectable levels of PC1/3 or PC2 were cotransduced
      with adenoviruses expressing rat proIAPP and either PC2 or PC1/3. As expected, in
      GH3 cells transduced to express only proIAPP, no processing was observed.
      Coexpression of proIAPP and PC2 resulted in production of mature IAPP, whereas in
      cells that coexpressed proIAPP and PC1/3 only a 6-kDa intermediate was produced.
      We conclude that PC1/3 is important for processing of proIAPP at the COOH
      terminus, but in its absence, PC2 can initiate complete processing of proIAPP to
      IAPP by cleaving the precursor at either its NH(2)- or COOH-terminal cleavage
      sites.

PMID- 14693709
TI  - Induction of beta-cell proliferation and retinoblastoma protein phosphorylation
      in rat and human islets using adenovirus-mediated transfer of cyclin-dependent
      kinase-4 and cyclin D1.
AB  - The major regulator of the gap-1/synthesis phase (G(1)/S) cell cycle checkpoint
      is the retinoblastoma protein (pRb), and this is regulated in part by the
      activities of cyclin-dependent kinase (cdk)-4 and the D cyclins. Surprisingly,
      given the potential importance of beta-cell replication for islet replacement
      therapy, pRb presence, phosphorylation status, and function have not been
      explored in beta-cells. Here, adenoviruses expressing cdk-4 and cyclin D(1) were
      used to explore rat and human pRb phosphorylation and beta-cell cycle control.
      pRb is present in rat and human islets, and overexpression of cyclin D(1)/cdk-4
      led to strikingly enhanced pRb phosphorylation in both species. Combined
      overexpression of both cdk-4 and cyclin D(1) caused a threefold increase in
      [(3)H]thymidine incorporation. This increase in proliferation was confirmed
      independently using insulin and bromodeoxyuridine immunohistochemistry, where
      human beta-cell replication rates were increased 10-fold. Cdk-4 or cyclin D(1)
      overexpression did not adversely effect beta-cell differentiation or function.
      The key cell cycle regulatory protein, pRb, can be harnessed to advantage using
      cyclin D(1)/cdk-4 for the induction of human and rodent beta-cell replication,
      enhancing replication without adversely affecting function or differentiation.
      This approach will allow detailed molecular study of the cellular mechanisms
      regulating the cell cycle in beta-cells, beta-cell lines, and stem cell-derived
      beta-cells.

PMID- 14693710
TI  - Mode of onset of type 2 diabetes from normal or impaired glucose tolerance.
AB  - Fasting plasma glucose concentrations (FPG) predict development of type 2
      diabetes. Whether hyperglycemia evolves from normoglycemia gradually over time or
      as a step increase is not known. We measured plasma glucose and insulin levels
      during oral glucose testing in 35- to 64-year-old men and nonpregnant women from
      a population-based survey (Mexico City Diabetes Study) at baseline (n = 2,279)
      and after 3.25 (n = 1,740) and 7 years (n = 1,711) of follow-up. In subjects with
      normal glucose tolerance (NGT) on all three occasions (nonconverters; n = 911),
      FPG increased only slightly (0.23 +/- 0.79 mmol/l, mean +/- SD; P < 0.0001) over
      7 years. In contrast, conversion to diabetes among NGT subjects (n = 98) was
      marked by a large step-up in FPG regardless of time of conversion (3.06 +/- 2.57
      and 2.94 +/- 3.11 mmol/l, respectively, at 3.25 and 7 years; P < 0.0001 vs.
      nonconverters). Likewise, in subjects who converted to diabetes from impaired
      glucose tolerance (n = 75), FPG rose by 3.14 +/- 3.83 and 3.12 +/- 3.61 mmol/l (P
      < 0.0001 vs. nonconverters). Three-quarters of converters had increments in FPG
      above the 90th percentile of the corresponding increments in nonconverters.
      Converters had higher baseline BMI (30.4 +/- 4.9 vs. 27.3 +/- 4.0 kg/m(2); P <
      0.001) and fasting plasma insulin values (120 +/- 78 vs. 84 +/- 84 pmol/l; P <
      0.02) than nonconverters; however, no consistent change in either parameter had
      occurred before conversion. In contrast, changes in 2-h postglucose insulin
      levels between time of conversion and preceding measurement were significantly (P
      < 0.0001) related to the corresponding changes in FPG in an inverse manner. We
      conclude that, within a 3-year time frame, the onset of diabetes is very often
      rapid rather than gradual and is in part explained by a fall in glucose
      stimulated insulin response.

PMID- 14693711
TI  - Long-term renal effects of a neutralizing RAGE antibody in obese type 2 diabetic
      mice.
AB  - Advanced glycation end products (AGEs) have been implicated in the pathogenesis
      of diabetic kidney disease. The actions of AGEs are mediated both through a non
      receptor-mediated pathway and through specific receptors for AGE (RAGEs). To
      explore a specific role for RAGE in renal changes in type 2 diabetes, we examined
      the renal effects of a neutralizing murine RAGE antibody in db/db mice, a model
      of obese type 2 diabetes. One group of db/db mice was treated for 2 months with
      the RAGE antibody, and another db/db group was treated for the same period with
      an irrelevant IgG. Two groups of nondiabetic db/+ mice were treated with either
      RAGE antibody or isotype-matched IgG for 2 months. Placebo-treated db/db mice
      showed a pronounced increase in kidney weight, glomerular volume, basement
      membrane thickness (BMT), total mesangial volume, urinary albumin excretion
      (UAE), and creatinine clearance compared with nondiabetic controls. In RAGE
      antibody-treated db/db mice, the increase in kidney weight, glomerular volume,
      mesangial volume, and UAE was reduced, whereas the increase in creatinine
      clearance and BMT was fully normalized. Notably, these effects in db/db mice were
      seen without impact on body weight, blood glucose, insulin levels, or food
      consumption. In conclusion, RAGE is an important pathogenetic factor in the renal
      changes in an animal model of type 2 diabetes.

PMID- 14693712
TI  - Regulation of the early subnormal retinal oxygenation response in experimental
      diabetes by inducible nitric oxide synthase.
AB  - We aimed to test the hypothesis that the inducible form of nitric oxide synthase
      (iNOS) contributes to the development of an early subnormal retinal oxygenation
      response in preclinical models of diabetic retinopathy. In urethane anesthetized
      Sprague Dawley rats or C57BL/6 mice, functional magnetic resonance imaging was
      used to noninvasively measure the change in retinal oxygen tension (Delta PO(2))
      during a carbogen-inhalation challenge. In the rat experiments, the retinal Delta
      PO(2) of the following groups were compared: control rats (n = 9), 3-month
      diabetic rats (n = 5), and 3-month diabetic rats treated orally with L-N(6)-(1
      iminoethyl)lysine 5-tetrazole amide, a prodrug of an inhibitor of iNOS (n = 6).
      In addition, the retinal Delta PO(2) of the following mouse groups were compared:
      C57BL/6 mice (n = 20), C57BL/6-Nos2(tm1 Lau) mice (n = 10), 4-month diabetic mice
      (n = 13), and 4-month diabetic knockout mice (n = 6). Only the Delta PO(2) of the
      superior hemiretina of the diabetic rat and mice groups were significantly
      subnormal (P < 0.05). The superior Delta PO(2) of the diabetic rats treated with
      the prodrug was not significantly (P > 0.05) different from their respective
      normal controls. In the mice experiments, the superior retinal Delta PO(2) of the
      iNOS null mice was not statistically different (P > 0.05) from that of normal
      control mice. iNOS is required for the development of an early subnormal Delta
      PO(2) in experimental diabetic retinopathy.

PMID- 14693713
TI  - Retinal vessel diameters and the incidence of gross proteinuria and renal
      insufficiency in people with type 1 diabetes.
AB  - Early retinal vessel caliber changes may predict risk of diabetic nephropathy. We
      examined the association of retinal vessel diameters and the incidence of gross
      proteinuria and renal insufficiency in a population-based cohort of people with
      type 1 diabetes (n = 557). Baseline retinal photographs were digitized, and
      diameters of individual retinal vessels were measured and summarized. Incident
      cases of gross proteinuria and renal insufficiency were identified over a 16-year
      period. Larger retinal venular diameter was associated with higher cumulative
      incidence of gross proteinuria (18.6, 25.4, 37.7, and 50.4%, comparing increasing
      venular diameter quartiles) and renal insufficiency (10.7, 15.5, 23.2, and
      32.8%). After adjusting for age, sex, duration of diabetes, HbA(1c) levels,
      baseline retinopathy levels, and other factors, larger retinal venular diameter
      was associated with an increased risk of gross proteinuria (RR 1.53, 95% CI 1.19
      1.97, comparing 4th vs. 1st to 3rd quartiles of venular diameter) and renal
      insufficiency (1.51, 1.05-2.17). Retinal arteriolar diameter was not associated
      with either gross proteinuria or renal insufficiency. We conclude that in
      individuals with type 1 diabetes, larger retinal venular diameter is
      independently associated with the long-term incidence of gross proteinuria and
      renal insufficiency and may provide additional predictive information regarding
      risk of nephropathy.

PMID- 14693714
TI  - Elevated mitochondrial cytochrome P450 2E1 and glutathione S-transferase A4-4 in
      streptozotocin-induced diabetic rats: tissue-specific variations and roles in
      oxidative stress.
AB  - Oxidative stress is an important factor in the etiology and pathogenesis of
      diabetes. We investigated changes in mitochondrial production of reactive oxygen
      species (ROS) and mitochondrial antioxidant defense systems in different tissues
      of streptozotocin (STZ)-induced diabetic rats. Our results show that increased
      ROS production and oxidative stress differentially affect mitochondrial and
      cytosolic glutathione (GSH) metabolism. Of the four tissues investigated, the
      pancreas, kidney, and brain appear to be affected more severely than the liver.
      We show a five- to eightfold increase of cytochrome P450 2E1 (CYP2E1) and
      glutathione S-transferase (GST) A4-4 levels in mitochondria from STZ-treated rat
      tissues compared with those in nondiabetic rat tissues, suggesting possible roles
      in the disease process. Transient transfection of COS cells with CYP2E1 cDNA
      caused a similar accumulation of CYP2E1 and GST A4-4 in mitochondria and
      increased production of mitochondrial ROS. Our results also show an increase in
      steady-state levels of Hsp70 in the mitochondrial and cytosolic fractions of
      different tissues of diabetic rats. These results indicate, for the first time, a
      marked increase in mitochondrial oxidative stress in target tissues of STZ
      treated rats and implicate a direct role for mitochondrial CYP2E1 in the
      generation of intramitochondrial ROS.

PMID- 14693715
TI  - Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of
      vascular complications of type 1 diabetes.
AB  - Type 1 diabetes is associated with reduced vascular repair, as indicated by
      impaired wound healing and reduced collateral formation in ischemia. Recently,
      endothelial progenitor cells (EPCs) have been identified as important regulators
      of these processes. We therefore explored the concept that EPCs are dysfunctional
      in diabetes. The number of EPCs obtained from type 1 diabetic patients in culture
      was 44% lower compared with age- and sex-matched control subjects (P < 0.001).
      This reduction was inversely related to levels of HbA(1c) (R = -0.68, P = 0.01).
      In addition, we demonstrated that patient EPCs were also impaired in function
      using an in vitro angiogenesis assay. Conditioned media from patient EPCs were
      significantly reduced in their capacity to support endothelial tube formation in
      comparison to control EPCs. Therefore, despite culturing the EPCs under
      normoglycemic conditions, functional differences between patient and control EPCs
      were maintained. Our findings demonstrate that adverse metabolic stress factors
      in type 1 diabetes are associated with reduced EPC numbers and angiogenicity. We
      hypothesize that EPC dysfunction contributes to the pathogenesis of vascular
      complications in type 1 diabetes.

PMID- 14693716
TI  - Peroxisome proliferator-activated receptor-gamma ligands inhibit TGF-beta 1
      induced fibronectin expression in glomerular mesangial cells.
AB  - The thiazolidinedione (TZD) class of antidiabetic drugs, which are ligands for
      peroxisome proliferator-activated receptor (PPAR)-gamma, has been shown to
      possess potent anti-inflammatory and antineoplastic actions. Here, we show in
      mesangial cells that PPAR-gamma agonists inhibit fibronectin expression by
      transforming growth factor (TGF)-beta 1. TGF-beta 1 enhanced fibronectin mRNA
      expression, and this enhancement was abrogated by pretreatment with pioglitazone.
      Electrophoretic mobility shift assay identified that pioglitazone inhibited TGF
      beta 1-induced DNA binding of activator protein-1 (AP-1). Pioglitazone inhibited
      AP-1 reporter activity but not Smad binding elements reporter activity without
      affecting TGF-beta 1-induced activation of mitogen-activated protein kinases
      (MAPKs) or Smad2. PPAR-gamma overexpression inhibited TGF-beta 1-induced
      fibronectin expression as well as the activation of AP-1. 15-Deoxy-Delta(12,14)
      prostaglandin J(2) (15d-PGJ(2)), a natural PPAR-gamma ligand, also inhibited TGF
      beta1-induced fibronectin expression by suppressing AP-1 activation by TGF-beta
      1. 15d-PGJ(2) inhibited the TGF-beta 1-induced MAPK activation. Dominant-negative
      PPAR-gamma (Delta PPAR-gamma) completely abrogated the inhibitory effect of
      pioglitazone and incompletely blocked its effect of 15d-PGJ(2) on TGF-beta 1
      induced AP-1 reporter activity. Delta PPAR-gamma overexpression did not affect
      the inhibitory effect of 15d-PGJ(2) on TGF-beta 1-induced MAPK activation. In
      conclusion, pioglitazone inhibits TGF-beta 1-induced fibronectin expression by
      inhibiting AP-1 activation dependent on PPAR-gamma, while 15d-PGJ(2) acts through
      a dual mechanism independent of and dependent on PPAR-gamma activation in mouse
      mesangial cells.

PMID- 14693717
TI  - Genetic variation at the adiponectin locus and risk of type 2 diabetes in women.
AB  - Previous data suggesting that polymorphisms in the adiponectin gene were
      associated with insulin resistance or type 2 diabetes have been inconsistent. We
      assessed the relationship between five common haplotype-tagging single nucleotide
      polymorphisms (SNPs) in the adiponectin gene (-11365C>G, -4034A>C, -3964A>G,
      +45T>G, and +276G>T), haplotypes defined by these SNPs, and the risk of type 2
      diabetes by conducting a nested case-control study of 642 incident cases of type
      2 diabetes and 995 matching control subjects in the Nurses' Health Study.
      Overall, we did not observe significant differences in genotype or allele
      frequencies for the five SNPs between the case and control subjects. After
      adjustment for diabetes risk factors, the -4034 C/C genotype was associated with
      a reduced risk of diabetes (odds ratio [OR] compared with the A/A genotype =
      0.70, 95% CI 0.50-0.99, P = 0.04). In subgroup analyses, the +276 genotype was
      significantly associated with diabetes risk only among subjects with peroxisome
      proliferator-activated receptor-gamma (PPAR gamma) variant 12Ala allele (OR
      comparing +276 T alleles with the G/G genotype = 1.69, 1.04-2.75, P = 0.035) or
      among obese subjects (1.46, 1.03-2.08, P = 0.03). These data suggest a potential
      interaction between the adiponectin genotype and PPAR gamma genotype or obesity,
      but these analyses should be considered exploratory and require further
      investigation in larger studies.

PMID- 14693718
TI  - Lipoprotein lipase is a gene for insulin resistance in Mexican Americans.
AB  - The insulin resistance syndrome is increasingly recognized as a risk factor for
      cardiovascular disease. Lipoprotein lipase (LPL) is a candidate gene for
      components of the syndrome. A small number of studies have demonstrated
      association of single nucleotide polymorphisms within LPL and indirect or
      surrogate measures of insulin resistance, largely based on glucose and insulin
      values obtained in the fasting state or during an oral glucose tolerance test. To
      test directly whether LPL is an insulin resistance gene, we performed the
      hyperinsulinemic-euglycemic clamp in a large family-based population of Mexican
      Americans who were genotyped at six polymorphisms in LPL that define the most
      common haplotypes in the population. LPL haplotypes showed linkage to the glucose
      infusion rate (GINF), a direct physiologic measurement of insulin sensitivity (P
      = 0.034). In addition, significant associations with GINF were demonstrated for
      the most common haplotype (P = 0.031) and the fourth most common haplotype (P =
      0.007). Haplotype 1 was associated with insulin sensitivity (mean GINF for
      haplotype 1 carriers = 383.0 mg/min) and haplotype 4 with insulin resistance
      (mean GINF for haplotype 4 carriers = 344.3 mg/min). This haplotype-based genetic
      analysis provides compelling evidence that variation in the LPL gene plays a role
      in determining insulin resistance in this ethnic group with a high prevalence of
      the insulin resistance syndrome.

PMID- 14693719
TI  - Familial hyperinsulinemic hypoglycemia caused by a defect in the SCHAD enzyme of
      mitochondrial fatty acid oxidation.
AB  - Inappropriately elevated insulin secretion is the hallmark of persistent
      hyperinsulinemic hypoglycemia of infancy (PHHI), also denoted congenital
      hyperinsulinism. Causal mutations have been uncovered in genes coding for the
      beta-cell's ATP-sensitive potassium channel and the metabolic enzymes glucokinase
      and glutamate dehydrogenase. In addition, one hyperinsulinemic infant was
      recently found to have a mutation in the gene encoding short-chain 3-hydroxyacyl
      CoA dehydrogenase (SCHAD), an enzyme participating in mitochondrial fatty acid
      oxidation. We have studied a consanguineous family with severe neonatal
      hypoglycemia due to increased insulin levels and where well-established genetic
      causes of hyperinsulinism had been eliminated. A genome-wide, microsatellite
      based screen for homozygous chromosomal segments was performed. Those regions
      that were inherited in accordance with the presupposed model were searched for
      mutations in genes encoding metabolic enzymes. A novel, homozygous deletion
      mutation was found in the gene coding for the SCHAD enzyme. The mutation affected
      RNA splicing and was predicted to lead to a protein lacking 30 amino acids. The
      observations at the molecular level were confirmed by demonstrating greatly
      reduced SCHAD activity in the patients' fibroblasts and enhanced levels of 3
      hydroxybutyryl-carnitine in their blood plasma. Urine metabolite analysis showed
      that SCHAD deficiency resulted in specific excretion of 3-hydroxyglutaric acid.
      By the genetic explanation of our family's cases of severe hypoglycemia, it is
      now clear that recessively inherited SCHAD deficiency can result in PHHI. This
      finding suggests that mitochondrial fatty acid oxidation influences insulin
      secretion by a hitherto unknown mechanism.

PMID- 14693720
TI  - Genome-wide search for type 2 diabetes/impaired glucose homeostasis
      susceptibility genes in the Chinese: significant linkage to chromosome 6q21-q23
      and chromosome 1q21-q24.
AB  - This genome-wide search for susceptibility genes to type 2 diabetes/impaired
      glucose homeostasis (IGH) was performed on a relatively homogeneous Chinese
      sample with a total number of 257 pedigrees and 385 affected sibpairs. Two
      regions showed significant linkage to type 2 diabetes/IGH in the Chinese. The
      region showing linkage to type 2 diabetes/IGH from the entire sample group
      analysis was located on chromosome 6q21-q23 (128.93 cM, 1-LOD [logarithm of odds]
      support interval between 124 and 142 cM, according to the Marshfield genetic
      map), with a maximum likelihood score of 6.23, a nonparametric linkage (all)
      score of 4.48, and empirical P value <0.001. With a subanalysis based on 101
      affected sibpairs with age at diagnosis of type 2 diabetes/IGH <40 years, we
      detected significant evidence for linkage to chromosome 1q21-q24 (192.1 cM, 1-LOD
      support interval between 182 and 197 cM), with a maximum likelihood score of
      8.91, a nonparametric linkage (all) score of 5.70, and empirical P value <0.001.
      No interaction was observed between these two regions. Our independent
      replication of the region on chromosome 1q that has been shown to be linked
      significantly to type 2 diabetes/IGH in Chinese supports the notion that gene(s)
      in this region may be universally important in the development of human type 2
      diabetes.

PMID- 14693721
TI  - The common -866 G/A polymorphism in the promoter of uncoupling protein 2 is
      associated with increased carbohydrate and decreased lipid oxidation in juvenile
      obesity.
AB  - Uncoupling protein (UCP) 2 is a member of the mitochondrial transporter
      superfamily that uncouples proton entry in the mitochondrial matrix from ATP
      synthesis. Although its physiological role remains to be established, UCP2 is
      considered a candidate gene for association with energy metabolism and obesity. A
      common promoter polymorphism, -866 G/A, has been associated with increased UCP2
      gene expression and middle-aged adult obesity. In fact, our analysis of 296
      juvenile obese and 568 nonobese control subjects revealed no difference in the
      prevalence of this polymorphism. Insulin and glucose response to oral glucose was
      comparable across the -866 genotypes. Metabolic studies in 147 of these juvenile
      obese subjects showed that homozygosity for the UCP2 promoter variant A was
      associated with important changes in energy metabolism compared with other
      genotypes, i.e., a 34% increase of carbohydrate oxidation (94 +/- 10 vs. 70 +/- 3
      mg.min(-1).m(-2), P = 0.004) and a 23% decrease of lipid oxidation (26 +/- 3 vs.
      34 +/- 1 mg.min(-1).m(-2), P = 0.03). Therefore, the juvenile obese subjects who
      are homozygous for the A variant have an increased ratio (3.6 +/- 1.2) of
      calories derived from carbohydrates to those from lipids compared with G/A or G/G
      obese children (1.4 +/- 0.2, P = 0.003), suggesting a role for UCP2 in the
      partitioning of metabolic fuels.

PMID- 14693722
TI  - Distinguishing covariation from causation in diabetes: a lesson from the protein
      disulfide isomerase mRNA abundance trait.
AB  - Protein disulfide isomerase (Pdi) is reported to be an insulin-regulated gene
      whose expression level is increased in the livers of rats with streptozotocin
      induced diabetes. We found that Pdi mRNA is approximately 20-fold more abundant
      in the diabetes-susceptible BTBR mouse strain relative to the diabetes-resistant
      C56BL/6 (B6) strain. A genetic analysis was carried out to determine whether
      there is a causal relationship between elevated Pdi expression and diabetes
      phenotype in BTBR-ob/ob mice. We mapped Pdi mRNA abundance as a quantitative
      trait in 108 (B6 x BTBR)F(2)-ob/ob mice segregating for diabetes. We detected a
      single linkage at the telomeric end of chromosome 11, where the Pdi gene itself
      resides (logarithm of odds score >30.0). No linkage was detected for the Pdi mRNA
      trait in the regions where we have previously identified quantitative trait loci
      for diabetes traits. Sequencing of the Pdi promoter and cDNA revealed several
      single nucleotide polymorphisms between these two mouse strains. We conclude that
      in our experimental model, elevated Pdi expression is cis regulated and is not
      linked to diabetes susceptibility. Genetic analysis is a powerful tool for
      distinguishing covariation from causation in expression array studies of disease
      traits.

PMID- 14693723
TI  - Identification of major quantitative trait loci controlling body weight variation
      in ob/ob mice.
AB  - The adipocyte hormone leptin constitutes an important component of the regulation
      of energy homeostasis; leptin-deficient animals, such as obese mice, are
      strikingly overweight. The seemingly uninhibited weight gain in obese mice belies
      the fact that control of energy homeostasis remains under precise, heritably
      modifiable control. Herein, we report large, heritable differences in body weight
      and food intake between BTBR-ob/ob and B6-ob/ob mice. We have identified two
      loci, called modifier of obese (Moo1 and Moo2), that explain the majority of the
      heritable variance in (BTBR x B6) F(2)-ob/ob mice. Using interval-specific
      congenic mouse lines, we mapped Moo1 to an 8-Mb segment of chromosome 2 and
      demonstrated that Moo1 exerts its effects primarily by regulating total fat mass.
      Although null alleles of leptin are rare, the majority of overweight adults are
      leptin resistant, suggesting that leptin-independent pathways, such as those
      studied here, are important regulators of energy homeostasis. Thus, the
      identification of these loci may provide important new insights into the
      pathogenesis of human obesity.

PMID- 14693724
TI  - C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials
      to preserve beta-cell function: report of an ADA workshop, 21-22 October 2001.
AB  - The underlying cause of type 1 diabetes, loss of beta-cell function, has become
      the therapeutic target for a number of interventions in patients with type 1
      diabetes. Even though insulin therapies continue to improve, it remains difficult
      to achieve normal glycemic control in type 1 diabetes, especially long term. The
      associated risks of hypoglycemia and end-organ diabetic complications remain.
      Retention of beta-cell function in patients with type 1 diabetes is known to
      result in improved glycemic control and reduced hypoglycemia, retinopathy, and
      nephropathy. To facilitate the development of therapies aimed at altering the
      type 1 diabetes disease process, an American Diabetes Association workshop was
      convened to identify appropriate efficacy outcome measures in type 1 diabetes
      clinical trials. The following consensus emerged: While measurements of immune
      responses to islet cells are important in elucidating pathogenesis, none of these
      measures have directly correlated with the decline in endogenous insulin
      secretion. HbA(1c) is a highly valuable clinical measure of glycemic control, but
      it is an insensitive measure of beta-cell function, particularly with the
      currently accepted standard of near-normal glycemic control. Rates of severe
      hypoglycemia and diabetic complications ultimately will be improved by therapies
      that are effective at preserving beta-cell function but as primary outcomes
      require inordinately large and protracted trials. Endogenous insulin secretion is
      assessed best by measurement of C-peptide, which is cosecreted with insulin in a
      one-to-one molar ratio but unlike insulin experiences little first pass clearance
      by the liver. Measurement of C-peptide under standardized conditions provides a
      sensitive, well accepted, and clinically validated assessment of beta-cell
      function. C-peptide measurement is the most suitable primary outcome for clinical
      trials of therapies aimed at preserving or improving endogenous insulin secretion
      in type 1 diabetes patients. Available data demonstrate that even relatively
      modest treatment effects on C-peptide will result in clinically meaningful
      benefits. The development of therapies for addressing this important unmet
      clinical need will be facilitated by trials that are carefully designed with beta
      cell function as determined by C-peptide measurement as the primary efficacy
      outcome.

PMID- 14693725
TI  - Molecular design and functional organization of the RecA protein.
AB  - The bacterial RecA protein participates in a remarkably diverse set of functions,
      all of which are involved in the maintenance of genomic integrity. RecA is a
      central component in both the catalysis of recombinational DNA repair and the
      regulation of the cellular SOS response. Despite the mechanistic differences of
      its functions, all require formation of an active RecA/ATP/DNA complex. RecA is a
      classic allosterically regulated enzyme, and ATP binding results in a dramatic
      increase in DNA binding affinity and a cooperative assembly of RecA subunits to
      form an ordered, helical nucleoprotein filament. The molecular events that
      underlie this ATP-induced structural transition are becoming increasingly clear.
      This review focuses on descriptions of our current understanding of the molecular
      design and allosteric regulation of RecA. We present a comprehensive list of all
      published recA mutants and use the results of various genetic and biochemical
      studies, together with available structural information, to develop ideas
      regarding the design of RecA functional domains and their catalytic organization.

PMID- 14693726
TI  - The protein components and mechanism of eukaryotic Okazaki fragment maturation.
AB  - An initiator RNA (iRNA) is required to prime cellular DNA synthesis. The
      structure of double-stranded DNA allows the synthesis of one strand to be
      continuous but the other must be generated discontinuously. Frequent priming of
      the discontinuous strand results in the formation of many small segments,
      designated Okazaki fragments. These short pieces need to be processed and joined
      to form an intact DNA strand. Our knowledge of the mechanism of iRNA removal is
      still evolving. Early reconstituted systems suggesting that the removal of iRNA
      requires sequential action of RNase H and flap endonuclease 1 (FEN1) led to the
      RNase H/FEN1 model. However, genetic analyses implied that Dna2p, an essential
      helicase/nuclease, is required. Subsequent biochemical studies suggested
      sequential action of RPA, Dna2p, and FEN1 for iRNA removal, leading to the second
      model, the Dna2p/RPA/FEN1 model. Studies of strand-displacement synthesis by
      polymerase delta indicated that in a reconstituted system, FEN1 could act as soon
      as short flaps are created, giving rise to a third model, the FEN1-only model.
      Each of the three pathways is supported by different genetic and biochemical
      results. Properties of the major protein components in this process will be
      discussed, and the validity of each model as a true representation of Okazaki
      fragment processing will be critically evaluated in this review.

PMID- 14693727
TI  - Children and increased susceptibility to environmental carcinogens: evidence or
      empathy?

PMID- 14693728
TI  - Vitamin D receptor gene polymorphisms and risk of prostate cancer: a meta
      analysis.
AB  - Several polymorphisms in the vitamin D receptor (VDR) gene have been implicated
      as risk factors for prostate cancer. We performed a meta-analysis of 14 studies
      (17 comparisons) with TaqI genotyping (1870 prostate cancer cases; 2843
      controls), 6 studies (8 comparisons) with poly(A) repeat genotyping (540 cases;
      870 controls), 5 studies with BsmI genotyping (987 cases; 1504 controls), and 3
      studies with FokI genotyping (514 cases; 545 controls). The random-effects odds
      ratio (OR) for the t versus T allele was 0.95 [95% confidence interval (CI), 0.86
      1.05]. There was no suggestion of an overall effect either in recessive or
      dominant modeling, and the comparison of t/t versus T/T also showed no
      differential prostate cancer susceptibility (OR, 0.88; 95% CI, 0.70-1.10). No
      effect of t was seen in subjects of European descent (nine comparisons; OR, 0.97;
      95% CI, 0.87-1.08), Asian descent (five comparisons; OR, 0.88; 95% CI, 0.66
      1.17), or African descent (three comparisons; OR, 0.94; 95% CI, 0.41-2.17). There
      was no between-study heterogeneity in any of these analyses. Overall, the random
      effects OR was 0.94 (95% CI, 0.75-1.18; no between-study heterogeneity) for the S
      versus L allele, 0.92 (95% CI, 0.63-1.35; P < 0.01 for heterogeneity) for the B
      versus b allele, and 1.03 (95% CI, 0.86-1.23; no between-study heterogeneity) for
      the f versus F allele. The meta-analysis shows that these four polymorphisms are
      unlikely to be major determinants of susceptibility to prostate cancer on a wide
      population basis.

PMID- 14693729
TI  - A prospective study of cruciferous vegetables and prostate cancer.
AB  - High intake of cruciferous vegetables may offer some protection against prostate
      cancer, but overall data are inconclusive. Thus, we examined the association
      between cruciferous vegetable intake and risk of prostate cancer in the Health
      Professionals Follow-Up Study. Between 1986 and 2000, 2,969 cases of nonstage T1a
      prostate cancer were diagnosed in 47,365 men who completed dietary assessments in
      1986, 1990, and 1994. We calculated the multivariate relative risk (RR) and 95%
      confidence intervals (CIs) using Cox regression. Overall, we found no appreciable
      association between baseline intake of cruciferous vegetables and risk of
      prostate cancer (RR, 0.93; 95% CI, 0.82-1.05, for > or = 5 versus < or = 1
      serving/week; P for trend = 0.30), and only a slight suggestive association for
      organ-confined prostate cancer (RR, 0.88; 95% CI, 0.74-1.05; P for trend = 0.06).
      The inverse association was stronger for men under the age of 65 years (RR, 0.81;
      95% CI, 0.64-1.02; P for trend = 0.02), especially for organ-confined cancers
      (RR, 0.72; 95% CI, 0.54-0.97; P for trend = 0.007). In addition, this inverse
      association was stronger when we restricted the analysis to men with more
      consistent intake of vegetables over the 10 years before 1986, when we limited
      the analysis to men who had had a prostate-specific antigen test, and when we
      considered an 8-year time lag. This study does not provide compelling evidence of
      a protective influence of cruciferous vegetables on prostate cancer risk.
      However, if cruciferous vegetables are protective early in prostate
      carcinogenesis, as suggested by proposed mechanisms, we may expect stronger
      associations, as observed, for more remote diet for prostate-specific antigen
      detected early stage (organ-confined) cancers in younger men. In contrast, for
      advanced cancers in older men, which were probably initiated decades in the past,
      recent dietary intakes of cruciferous vegetables may be irrelevant. These
      findings suggest that future studies of cruciferous vegetables should focus on
      early stages of prostate cancer.

PMID- 14693730
TI  - Endogenous sex hormones and prostate cancer risk: a case-control study nested
      within the Carotene and Retinol Efficacy Trial.
AB  - To examine whether endogenous androgens influence the occurrence of prostate
      cancer, we conducted a nested case-control study among participants enrolled in
      the Carotene and Retinol Efficacy Trial. We analyzed serum samples of 300 cases
      diagnosed between 1987 and 1998, and 300 matched controls. Higher concentrations
      of testosterone (T) were not associated with increased prostate cancer risk.
      Relative to men with levels in the lowest fourth of the distribution, men in the
      upper fourth of total T had a risk of 0.82 [95% confidence interval (CI), 0.52
      1.29]. The corresponding relative risks for free T (0.72; 95% CI, 0.45-1.14),
      percentage of free T (0.74; 95% CI, 0.46-1.19), and total T:sex hormone binding
      globulin ratio (0.52; 95% CI, 0.32-0.83) similarly were not elevated. Higher
      concentrations of androstenedione, dehydroepiandrosterone sulfate, and 3 alpha
      androstanediol glucuronide were weakly associated with risk. Relative risks
      associated with being in the highest fourth for androstenedione,
      dehydroepiandrosterone sulfate, and 3 alpha-androstanediol glucuronide were 1.20
      (95% CI, 0.76-1.89), 1.38 (95% CI, 0.86-2.21), and 1.27 (95% CI, 0.80-2.00),
      respectively. Men in the upper fourth of total estradiol (E2), free E2 and
      percentage of free E2 had relative risks of 0.71 (95% CI, 0.42-1.13), 0.52 (95%
      CI, 0.33-0.82), and 0.65 (95% CI, 0.40-1.05), respectively. The inverse
      association between E2 and prostate cancer risk was largely restricted to men
      with blood collection within 3 years of diagnosis. Our results add to the
      evidence that serum testosterone is unrelated to prostate cancer incidence. The
      suggestions that intraprostatic androgen activity may increase risk and that
      serum estrogens may decrease risk, warrant additional study.

PMID- 14693731
TI  - Body size and composition and prostate cancer risk.
AB  - Reported associations between body measurements and the risk of prostate cancer
      are weak and inconsistent, possibly because some measures used do not
      differentiate between adipose and nonadipose tissue, body components that would
      theoretically have different associations with prostate cancer. Some studies have
      addressed this problem by estimating lean body mass from subjects' age, height,
      and weight. In a prospective cohort study of men 27-75 years of age at
      recruitment in 1990-1994, body measurements were taken by trained interviewers.
      Nonadipose and adipose mass were calculated from bioelectric impedance analysis.
      Incident prostate cancers were ascertained by use of the population cancer
      registry. Altogether 16,336 men contributed 113,535 person-years and 477 cancers,
      of which 79 were "aggressive," to the analysis. We found no overall association
      between prostate cancer and any anthropometric measurement. Analysis stratified
      by cancer aggressiveness revealed modest associations between measures of
      adiposity and the risk of aggressive disease. On the basis of the WHO cut points
      and compared with men in the normal range of body mass index, the risk ratio for
      obese men was 2.2 (95% confidence interval, 1.2-4.1). For each 10-kg increase in
      fat mass, the risk ratio was 1.4 (95% confidence interval, 1.0-1.8). Energy
      imbalance may play a role in the development of aggressive prostate cancer.

PMID- 14693732
TI  - Fatty acids and risk of prostate cancer in a nested case-control study in male
      smokers.
AB  - There is some evidence that alpha-linolenic acid might be positively related to
      prostate cancer risk. Associations between serum fatty acid composition as well
      as fatty acid intakes and prostate cancer risk were examined in the Alpha
      Tocopherol, Beta-Carotene Cancer Prevention Study. The cohort included 29,133
      male smokers aged 50-69 years. During 5-8 years of follow-up, 246 prostate cancer
      cases were diagnosed. One control was selected and matched by age (+/- 1 month)
      for each case from the cohort subjects alive and free of prostate cancer at the
      time the case was diagnosed. This study included 198 case-control pairs with
      baseline serum sample available for both. Fatty acids of serum cholesterol esters
      were measured as a percentage of total fatty acids, using capillary gas
      chromatography. Intakes of fatty acids were assessed from a validated self
      administered dietary questionnaire. Serum and dietary fatty acids had no
      consistent association with prostate cancer risk. Serum alpha-linolenic acid was
      not related to prostate cancer risk. Twofold risk was found in the highest
      quartile of serum myristic acid compared with the lowest quartile (odds ratio,
      1.93; 95% confidence interval, 1.02-3.64). alpha-Tocopherol supplementation
      modified the association between serum linoleic acid and prostate cancer risk (P
      for interaction 0.03); odds ratio was 0.17 (95% confidence interval, 0.04-0.68)
      in the highest quartile of serum linoleic acid compared with the lowest quartile
      in men who received alpha-tocopherol, whereas no association was found in men who
      did not receive alpha-tocopherol. In conclusion, we found no overall association
      between serum or dietary alpha-linolenic acid or any other unsaturated fatty acid
      and prostate cancer risk, but high serum linoleic acid was associated with lower
      risk in men supplemented with alpha-tocopherol. High serum myristic acid
      associated with an increased risk of prostate cancer.

PMID- 14693733
TI  - Comprehensive assessment of candidate genes and serological markers for the
      detection of prostate cancer.
AB  - We examined whether selected polymorphisms in 11 candidate genes and serum levels
      of insulin-like growth factor I (IGF-I) help predict the presence of prostate
      cancer among patients prescreened with prostate-specific antigen (PSA) and
      digital rectal exam (DRE). We studied 1031 consecutive men who underwent one or
      more prostate biopsies because of an elevated PSA level (>4 ng/ml) or an abnormal
      DRE. Eleven candidate genes were examined, including the androgen receptor,
      SRD5A2, CYP17, CYP3A4, vitamin D receptor, PSA, GST-T1, GST-M1, GST-P1, IGF-I,
      and IGF binding protein 3. We also measured serum IGF-I levels before biopsy. Of
      the 1031 men, 483 had cancer on any biopsy (cases) and 548 men had no cancer
      (controls). Age, ethnicity, total PSA, and DRE result were strongly predictive of
      the presence of prostate cancer. The mean IGF-I level for cases (119.4 ng/ml) was
      lower than for controls (124.4 ng/ml, P = 0.05) and were not predictive for the
      presence of prostate cancer. We found no associations between the androgen
      receptor, SRD5A2, CYP17, CYP3A4, vitamin D receptor, GST-M1, GST-P1, and IGF
      binding protein 3 genotypes and prostate cancer risk. The adjusted odds ratios
      for having prostate cancer for patients with the GST-T1 and IGF-I variant alleles
      were 1.64 (95% confidence interval, 1.1-2.4; P = 0.01) and 1.70 (95% confidence
      interval, 1.1-2.7; P = 0.02), respectively. Nine of 11 candidate genes were not
      significantly predictive for prostate cancer in a clinical setting. The GST-T1
      and IGF-I polymorphisms demonstrated modest associations with prostate cancer
      risk. IGF-I levels were not helpful in identifying patients with prostate cancer
      at the time of biopsy.

PMID- 14693734
TI  - Meningioma: is there an association with human leukocyte antigens?
AB  - The expression of human leukocyte antigen (HLA) alleles plays an important role
      in the development and recurrence of benign and malignant diseases. Association
      of single HLA alleles or haplotypes with neoplastic processes has been
      investigated previously, and correlation between HLA and solid tumors, such as
      head and neck cancers or uterine cervical squamous epithelial lesions, were
      reported. However, there is no published data on the influence of the HLA system
      on the development of symptomatic cerebral meningioma, a mostly benign
      intracranial tumor of mesenchymal origin in adults. The present investigation is
      comparing the frequency of single HLA alleles and haplotypes in 81 adult
      Caucasian patients with symptomatic central nervous system meningiomas to that of
      157 area- and race-matched healthy controls. Both standard serological and
      molecular genetic (PCR) techniques were used for HLA typing. Our results suggest
      an association between single HLA alleles and occurrence of clinically
      symptomatic meningioma. Patients with HLA-A*02 had a 2.5-fold increased risk of
      meningioma (P = 0.02), and those with HLA-DQB1*05 had a 1.8-fold increased risk
      of meningioma (P = 0.05). Conversely, HLA-A*01, -B*08, and -DRB1*03 were
      associated with a 0.4-, 0.5-, and 0.5-fold, respectively, decreased risk of
      meningioma (P = 0.008, P = 0.05, and P = 0.04). Moreover, the occurrence rate of
      combinations and estimated haplotypes containing these HLA alleles was strikingly
      different in meningioma patients compared with controls: significantly increased
      for the haplotypes HLA-A*02:DRB1*04 (P = 0.02, relative risk = 2.5) and HLA
      A*02:DRB1*04:DQB1*0302,DQB1*05 (P = 0.03, RR = 7.5), and significantly decreased
      for the haplotype HLA-A*01:B*08:DRB1*03 (P = 0.01, relative risk = 0.2). In
      conclusion, these data suggest that some single HLA alleles and haplotypes may
      protect from or predispose to developing symptomatic central nervous system
      meningioma during adult life. These associations may be indicative of the
      involvement of the immune system in the host antitumor surveillance, recognition,
      and destruction of de novo arising human tumor cells.

PMID- 14693735
TI  - Cancer in first-degree relatives and risk of glioma in adults.
AB  - Relatively few studies have examined glioma risk in relation to history of cancer
      in first-degree relatives. We sought to describe such risks in a large hospital
      based case-control study. Histologically confirmed incident adult glioma cases (n
      = 489) were identified at three regional referral hospitals between June 1994 and
      August 1998. Controls (n = 799) admitted to the same hospitals for nonmalignant
      conditions were frequency-matched on age, sex, race/ethnicity, hospital, and
      proximity of residence to hospital. Participants received a personal interview,
      including questions regarding cancer in family members. Odds ratios (ORs) were
      calculated to estimate the risk of glioma associated with a history of cancer in
      a first-degree relative using conditional logistic regression and compared with
      standardized incidence ratios among relatives of cases versus relatives of
      controls. Among participants reporting a family history of a brain cancer or a
      brain tumor, risk of glioma was 1.6 [95% confidence interval (CI), 0.5-5.3; n =
      5] and 3.0 (95% CI, 0.9-10.8; n = 7), respectively, in comparison with those
      without such family histories. Participants who had a family history of stomach
      (OR, 2.2; 95% CI, 1.0-4.6), colon (OR, 1.4; 95% CI, 0.9-2.2), or prostate cancer
      (OR, 2.1; 95% CI, 1.1-3.8) or Hodgkin disease (OR, 2.4; 95% CI, 0.9-6.3) had an
      increased glioma risk. OR estimates were similar to the ratios of standardized
      incidence ratios for cancer in relatives of cases versus controls. Shared
      environmental or genetic factors in families may influence glioma risk. Our
      findings suggest that individuals with a family history of specific cancers other
      than glioma may have an increased glioma risk.

PMID- 14693736
TI  - Immune profiling of plasma and cervical secretions using recycling immunoaffinity
      chromatography.
AB  - Small volumes of cervical secretions have limited measurements of immunity at the
      cervix, which may be important to studies of human papillomavirus (HPV). We
      report the use of recycling immunoaffinity chromatography to efficiently study
      immune profiles in cervical secretions. Frozen pairs of plasma and cervical
      secretions (collected on ophthalmic sponges) were selected randomly from women
      with normal cervical cytology (n = 50) participating in a natural history study
      of HPV in Guanacaste, Costa Rica. Single 25- micro l aliquots of plasma and
      (diluted) cervical secretions were assayed for interleukin (IL) -1 beta, -2, -4, 
      6, -8, -10, -12, -13, -15, IFN-alpha, -beta, -gamma, tumor necrosis factor-alpha,
      -beta, RANTES (regulated on activation normal T-cell express and secreted), MCP-1
      (monocyte chemoattractant protein), -2, -3, macrophage inflammatory protein-1
      alpha, -1 beta (regulated on activation normal T-cell express and secreted),
      macrophage colony-stimulating factor, IgG, IgA, and cyclooxygenase 2. All of the
      specimens were tested as blind replicates, and refrozen plasma was retested 4
      months later. To evaluate the reproducibility of the repeat measurements and to
      examine the correlation between plasma and cervical secretions, we calculated
      kappa values with 95% confidence intervals among categorized analyte values and
      Spearman correlation coefficients (rho) among detectable, continuous analyte
      values. Measurements of all of the analytes in either plasma or cervical
      secretions were highly reproducible, with all of the kappa > or = 0.78 (70% above
      0.90), and all of the rho > or = 0.88 (96% above 0.90). Only IL-1 beta (kappa =
      0.60 and rho = 0.82) and IL-6 (kappa = 0.50 and rho = 0.78) levels were strongly
      correlated between plasma and cervical secretions. IFN-gamma, tumor necrosis
      factor-beta, RANTES, MCP-1, MCP -2, macrophage inflammatory protein-1 alpha, and
      macrophage colony-stimulating factor levels were especially poorly correlated
      between plasma and cervical secretions (kappa < or = 0.25 and rho < or = 0.25).
      We conclude that recycling immunoaffinity chromatography is a reproducible method
      of measuring immune profiles from biological specimens, and immune profiles are
      not well correlated between plasma and cervical secretions, perhaps necessitating
      cervical collections to study cervix-specific immunity in HPV natural history
      studies.

PMID- 14693737
TI  - Free estradiol and breast cancer risk in postmenopausal women: comparison of
      measured and calculated values.
AB  - Mathematical methods exist to determine the fractions of sex hormones bound to
      albumin, bound to sex hormone binding globulin (SHBG), or unbound, using total
      hormone concentration and SHBG concentration. We used data from eight prospective
      studies of postmenopausal women to assess the validity of these estimates for
      fractions of estradiol (E2) and to investigate the impact of using calculated
      values in breast cancer relative risk (RR) models. Comparisons were made between
      measured and calculated concentrations of free and non-SHBG-bound E2 in four
      studies. Relationships between the hormone fractions were investigated and a
      sensitivity analysis of the calculation performed. Breast cancer RRs were
      estimated using conditional logistic regression by quintiles of free E2. There is
      a high correlation (r > 0.91) between calculated and measured values of both free
      and non-SHBG-bound E2. The calculation is highly sensitive to total hormone
      concentration but is relatively insensitive to SHBG concentration. In studies
      with both measured and calculated values, the RRs of breast cancer by quintile of
      free E2 were almost identical for both estimates; using calculated values in all
      possible studies the RR in the highest compared with the lowest quintile of free
      E2 was 2.29 (95% confidence interval, 1.65-3.19). The mathematical method used to
      calculate fractions of E2 is valid, and RR analyses using calculated values
      produce similar results to those using measured values. This suggests that for
      epidemiological studies, it is only necessary to measure total E2 concentration
      and SHBG concentration, with hormone fractions being obtained by calculation,
      producing savings in cost, time, and serum.

PMID- 14693738
TI  - A population-based case-control study of the Arg399Gln polymorphism in DNA repair
      gene XRCC1 and risk of breast cancer.
AB  - XRCC1 (X-ray repair cross-complementing group 1) is a base excision repair
      protein that plays a central role in the repair of DNA base damage and strand
      breaks. A common polymorphism (Arg-->Gln) at codon 399 of the XRCC1 gene has been
      previously linked to functional changes of the gene product and risk of cancers.
      We evaluated the association between XRCC1 Arg399Gln polymorphism and breast
      cancer risk in the population-based Shanghai Breast Cancer Study involving 1088
      cancer patients and 1182 community controls. Genomic DNA from peripheral blood
      was used in genotyping assays, and exposure information and anthropometrics were
      collected through in-person interview. Plasma estrogen and sex hormone-binding
      globulin (SHBG) levels were measured for 190 postmenopausal breast cancer
      patients who had donated a pretreatment blood sample and 407 postmenopausal
      controls. Conditional logistic regression model was used to estimate odds ratios
      (ORs) and 95% confidence intervals (95% CIs) adjusting potential confounders.
      Approximately 27% of controls carried the variant allele (Gln), and cases and
      controls had a similar distribution for both allele type and genotype of this
      polymorphism. We found that 7.8% of cases and 6.3% of controls were homozygous
      for the variant allele, resulting in an OR of 1.20 (95% CI, 0.85-1.69). The OR
      was slightly higher among younger women [<45 years of age (OR, 1.39; 95% CI, 0.82
      2.36)] than older women [> or = 45 years of age (OR, 1.07; 95% CI, 0.68-1.67)],
      but neither OR was statistically significant. No modifying effect of major breast
      cancer risk factors, including years of menstruation, body mass index, waist:hip
      ratio, and blood estrogen levels, was noted. Homozygosity for the variant Gln
      allele was associated with an elevated risk of postmenopausal breast cancer among
      subjects with a higher blood level of SHBG (OR, 3.27; 95% CI, 1.16-9.20) and a
      reduced risk among those with a lower level of SHBG (OR, 0.60; 95% CI, 0.18
      1.97). The overall results of the study suggest that Arg399Gln polymorphism of
      the XRCC1 gene alone may not play a substantial role in the risk of breast cancer
      among Chinese women.

PMID- 14693739
TI  - Effect of raloxifene on insulin-like growth factor-I, insulin-like growth factor
      binding protein-3, and leptin in premenopausal women at high risk for developing
      breast cancer.
AB  - Elevated insulin-like growth factor I (IGF-I) is associated with an increased
      risk for developing breast cancer in premenopausal women, whereas lower leptin
      levels have been documented in premenopausal breast cancer cases. We determined
      the effect of raloxifene on IGF-I, insulin-like growth factor binding protein 3
      (IGFBP-3), and leptin in premenopausal women at high risk for developing invasive
      breast cancer. Twenty-eight premenopausal women (median age 43 years)
      participating in a pilot breast cancer prevention trial provided 56 matched serum
      samples. Specimens were collected at baseline and after treatment with 60 mg of
      raloxifene daily. Median treatment duration was 3 months (range: 6 weeks to 12
      months). Samples were frozen at -70 degrees C until analysis. IGF-I, IGFBP-3, and
      leptin were measured by ELISA. Significance was evaluated by the Wilcoxon signed
      rank test. Raloxifene administration increased serum IGFBP-3 [mean change 245
      ng/ml; P = 0.017; 95% confidence interval (CI), 76-415] and leptin (mean change
      2.1 ng/ml; P = 0.005; 95% CI, 0.6-3.7). No significant change in serum IGF-I was
      detected (mean change 2.6 ng/ml; P = 0.84; 95% CI, -15.4 to 20.6). IGF-I:IGFBP-3
      molar ratio was stable (mean change -0.014; P = 0.30; 95% CI, -0.041 to 0.012).
      Raloxifene administration is associated with an increase in IGFBP-3 and leptin in
      premenopausal high risk women. Increases in IGFBP-3 may potentially decrease the
      activity of circulating IGF-I. The effect of modulating the IGF pathway and
      leptin on breast cancer risk needs additional evaluation.

PMID- 14693740
TI  - Adipose concentrations of organochlorine compounds and breast cancer recurrence
      in Long Island, New York.
AB  - Several studies have measured the association between blood or adipose
      concentrations of organochlorinated compounds (OCs), such as pesticides and
      polychlorinated biphenyls (PCBs), and breast cancer. The estrogenic effects of
      OCs might adversely affect breast cancer recurrence. The participants were 224
      women with nonmetastatic breast cancer enrolled in a New York-based case-control
      study. Supercritical fluid extraction followed by gas chromatography was
      conducted on adipose surgical specimens to determine OC concentrations. The mean
      follow-up time from surgery was 3.6 years. Thirty women (13.4%) were diagnosed
      with a recurrence. The concentration of pesticides and PCBs was correlated with
      baseline age and body mass index, but not with cancer stage. The highest tertile
      of total PCB concentration was associated with an increased risk of recurrence
      [relative risk (RR), 2.9; 95% confidence interval (CI), 1.02-8.2 versus the
      lowest tertile]. The risk for the highest tertile of the PCB congener
      Ballschmiter and Zell 118 was 4.0 (95% CI, 1.3-4.9). There was an increased risk
      for the middle level of the most abundant pesticide, 1,1-dichloro-2,2-di(4
      chlorophenyl)ethylene (RR, 2.3; 95% CI, 0.9-5.7), and for beta
      hexachlorocyclohexane, but not for their highest levels. Self-reported home
      termiticide exposure, alcohol consumption (> or = 1 drink/day), and race were not
      associated with prognosis. The RR for current cigarette smoking at diagnosis was
      2.1 (95% CI, 0.9-5.1). In contrast to previous data showing no relationship
      between OC exposure and risk of breast cancer in these women, adipose PCB
      concentrations were associated with tumor recurrence. Pesticide levels were not
      related to recurrence.

PMID- 14693741
TI  - Modeling familial clustered breast cancer using published data.
AB  - The purpose of this research was to model the familial clustering of breast
      cancer and to provide an accurate risk estimate for individuals from the general
      population, based on their family history of breast and ovarian cancer. We
      constructed a genetic model as an extension of a model by Claus et al. (E. B.
      Claus et al., Am. J. Hum. Genet., 48: 232-242, 1991), with three breast cancer
      genes, BRCA1, BRCA2, and a hypothetical BRCAu, in two variants, one in which
      BRCAu was dominant and one in which BRCAu was recessive. The model parameters
      were estimated using published estimates of population incidence and relative
      risks. Risk estimation was performed for a set of 196 counselees and for a set of
      simulated counselees with both the dominant BRCAu and the recessive BRCAu model,
      and compared relating to medical management. Estimates of the model parameters
      were found. Relative risks among family members were comparable between the model
      of Claus et al. (E. B. Claus et al., Am. J. Hum. Genet., 48: 232-242, 1991) and
      our model. The dominant and the recessive model provided approximately similar
      lifetime risks for breast cancer. Our model is suitable for breast cancer risk
      estimation in a health care setting.

PMID- 14693742
TI  - The cyclooxygenase-2 inhibitor, celecoxib, prevents the development of mammary
      tumors in Her-2/neu mice.
AB  - Evidence is now available showing that cyclooxygenase (COX)-2, which is involved
      in prostaglandin production, is overexpressed in many types of tumors including
      breast. Several reports have indicated that HER-2/neu-positive breast tumors are
      associated with an increased amount of COX-2 protein. In this study, we evaluated
      the effectiveness of the select COX-1 and COX-2 inhibitors in preventing mammary
      tumor development in HER-2/neu transgenic mice. At 4 weeks of age, female HER
      2/neu mice were fed a #5020 rodent diet supplemented with 900 ppm celecoxib, a
      COX-2 inhibitor, 64 ppm of SC560, a COX-1 inhibitor, or the unsupplemented #5001
      diet (control). The incidence of mammary tumors was significantly lower in the
      celecoxib-fed mice (71%; P = 0.001 versus control) than in the control mice (95%)
      or in the SC560-fed mice (91%). Celecoxib-treated mice also developed fewer
      tumors (1.3 +/- 1.1 SD; P = 0.039 versus control) than the control mice (2.2 +/-
      1.2) or the SC560 treated mice (2.3 +/- 1.3). The median time to tumor
      development was 266 days in the control group versus 291 days in the celecoxib
      treated group (P = 0.003 versus control). Lung metastasis was also reduced by
      treatment with celecoxib. The COX-1 inhibitor SC560 had no protective effect. The
      protection offered by celecoxib was associated with significantly lower
      concentrations of prostacyclin and prostaglandin E(2) in mammary tumors and their
      adjacent mammary glands. Our findings provide additional preclinical evidence to
      support the clinical studies to investigate the potential effectiveness of COX-2
      inhibitors in protecting woman who are at high risk for breast cancer.

PMID- 14693743
TI  - Alcohol consumption, smoking, and subsequent risk of colorectal cancer in middle
      aged and elderly Japanese men and women: Japan Public Health Center-based
      prospective study.
AB  - Few studies have examined the association of alcohol consumption and cigarette
      smoking with colorectal cancer in Asian populations whose genetic susceptibility
      to these factors are different from Western populations. We investigated this
      association and the joint effect of these factors, and estimated the population
      attributable fraction to clarify the public health impact on a Japanese
      population, based on a prospective study. We analyzed the 10-year (cohort I) and
      7-year (cohort II) follow-up data of the Japan Public Health Center-based
      prospective study on cancer and cardiovascular disease, derived from 90,004
      (42,540 male and 47,464 female) middle-aged and elderly Japanese. We identified
      716 (457 in men and 259 in women) newly diagnosed cases of colorectal cancer.
      Both alcohol consumption and smoking were clearly associated with colorectal
      cancer in men, after adjusting for age, family history of colorectal cancer, body
      mass index, and physical exercise. Regular heavy drinking of 150 g/week or more
      of ethanol showed a statistically significant increased risk compared with
      nondrinkers: relative risks (RRs) were 1.4 [95% confidence interval (CI), 1.1
      1.9] for 150-299 g/week and 2.1 (95% CI, 1.6-2.7) for 300 g/week or more. On the
      contrary, regular ethanol consumption was not associated with colorectal cancer
      (RR, 0.7; 95% CI, 0.4-1.1) in women. In terms of smoking, the RRs were 1.4 (95%
      CI, 1.1-1.8) for current smokers and 1.3 (95% CI, 0.98-1.7) for ex-smokers
      compared with never-smokers in men. The risk of smoking in women was similar to
      that in men, although not statistically significant. The colorectal cancer risk
      with 300 g/week or more of ethanol in current smokers was estimated at 3.0 (95%
      CI, 1.8-5.1) compared with nondrinkers among nonsmokers in men. Colorectal cancer
      attributable to alcohol consumption or smoking was estimated to be 46%. In
      conclusion, approximately half of the colorectal cancer cases may be preventable
      by tobacco and alcohol controls in middle-aged and elderly Japanese men.

PMID- 14693744
TI  - r-1,t-2,3,c-4-Tetrahydroxy-1,2,3,4-tetrahydrophenanthrene in human urine: a
      potential biomarker for assessing polycyclic aromatic hydrocarbon metabolic
      activation.
AB  - Individual differences in the metabolic activation and detoxification of
      carcinogenic polycyclic aromatic hydrocarbons (PAHs) may influence cancer risk.
      This has been investigated in many studies using genotyping approaches, but the
      results to date have been inconsistent. We propose that carcinogen metabolite
      phenotyping would be a more reliable way to determine the role of host metabolism
      in PAH-related cancer. Many PAHs are metabolically activated by formation of bay
      region diol epoxides. Phenanthrene, generally considered to be noncarcinogenic,
      is the simplest PAH with a bay region and is metabolized to diol epoxides by the
      same enzymes and with the same stereochemistry as the prototypic carcinogenic
      PAH, benzo[a]pyrene. The major end product of this metabolic activation pathway
      is r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (trans, anti-PheT).
      We have developed a method for the analysis of trans, anti-PheT in human urine. r
      1,t-2,4,c-3-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (trans, syn-PheT) was
      used as internal standard. After hydrolysis by beta-glucuronidase and sulfatase,
      solid phase extraction, and high-performance liquid chromatography collection,
      the sample was silylated and analyzed by gas chromatography-negative ion chemical
      ionization-mass spectrometry-selected ion monitoring at m/z 372. The resulting
      chromatograms were remarkably clean and trans, anti-PheT was readily detected in
      all human urine samples. Levels of trans, anti-PheT were 791 +/- 363 pmol/mg
      creatinine (n = 20) in psoriasis patients treated with a PAH-containing ointment,
      25.7 +/- 16.8 pmol/mg creatinine (n = 32) in coke oven workers exposed to PAH,
      4.58 +/- 2.95 pmol/mg creatinine (n = 31) in smokers, and 1.51 +/- 1.15 pmol/mg
      creatinine (n = 30) in nonsmokers. Levels of trans, anti-PheT correlated with
      levels of 1-hydroxypyrene in the urine of coke oven workers, smokers, and
      nonsmokers. Thus, trans, anti-PheT appears to be an excellent biomarker of PAH
      uptake. Levels of trans, anti-PheT were 8,000-19,000 times higher than those of
      the corresponding metabolite of benzo[a]pyrene. The results of this study
      demonstrate that trans, anti-PheT can be detected in human urine. We propose that
      measurement of this metabolite of phenanthrene may be important as part of a
      carcinogen metabolite-phenotyping approach to determine individual response to
      PAH exposure.

PMID- 14693745
TI  - Meta- and pooled analyses of GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes and risk
      of head and neck cancer.
AB  - Sequence variation in the GSTM1, GSTT1, GSTP1, and CYP1A1 genes may potentially
      alter susceptibility to head and neck cancers, although evidence from previous
      studies has not been consistent. To explore these associations, we conducted a
      meta-analysis of 31 published case-control studies (4635 cases and 5770 controls)
      and a pooled analysis of original data from nine published and two unpublished
      case-control studies (2334 cases and 2766 controls). In the meta-analysis, the
      summary odds ratios (ORs) for head and neck cancer were 1.23 [95% confidence
      interval (95% CI), 1.06-1.42] for the GSTM1 null genotype, 1.17 (95% CI, 0.98
      1.40) for the GSTT1 null genotype, 1.10 (95% CI, 0.92-1.31) for carrying the
      GSTP1 Val105 allele, and 1.35 (95% CI, 0.95-1.82) for carrying the CYP1A1 Val462
      allele. The pooled analysis ORs were 1.32 (95% CI, 1.07-1.62) for the GSTM1 null
      genotype, 1.25 (95% CI, 1.00-1.57) for the GSTT1 null genotype, 1.15 (95% CI,
      0.86-1.53) for carrying the GSTP1 Val105 allele, and 0.98 (95% CI, 0.75-1.29) for
      carrying the CYP1A1 Val462 allele. Increasing risk of head and neck cancer was
      observed with inheritance of increasing numbers of modest risk genotypes at the
      three GST loci (P for trend = 0.04), with the combination of carrying the GSTM1
      null, GSTT1 null, and GSTP1 Val105 alleles conferring an OR of 2.06 (95% CI, 1.11
      3.81). In conclusion, both the meta- and pooled analysis support modest
      associations of GSTM1 and GSTT1 genotypes with head and neck cancer risk, and our
      pooled analysis supports the notion of greater risk when genotypes at multiple
      GST loci are considered in a multigenic model.

PMID- 14693746
TI  - Loss of aurora A/STK15/BTAK overexpression correlates with transition of in situ
      to invasive ductal carcinoma of the breast.
AB  - The biological mechanisms involved in the progression of ductal carcinoma in situ
      (DCIS) to invasive breast cancer are not fully understood. We previously have
      shown that the putative oncogene Aurora-A/STK15/BTAK, encoding a centrosome
      associated kinase that regulates centrosomes and chromosome segregation, is
      amplified in human breast cancer. In this study, 37 archival breast tissue
      specimens of histologically confirmed DCIS lesions with adjacent invasive
      carcinoma and morphologically nonmalignant mammary ducts were analyzed
      immunohistochemically for expression of STK15. Statistically significant
      differences in overexpression of STK15 was found between invasive cancer and
      either nonmalignant mammary ducts (P < 0.0001) or DCIS lesions (P < 0.0005).
      Abnormalities in centrosome size and number was detected in the samples analyzed
      and 56% (14 of 25) of the cases also showed aneuploidy reflected in >2 signals of
      chromosome 3 and 17. Our data demonstrate that STK15 overexpression correlates
      with centrosome anomaly and aneuploidy in DCIS, and loss of STK15 overexpression
      is associated with progression of in situ to ductal invasive breast carcinoma.

PMID- 14693747
TI  - Geographic excess of estrogen receptor-positive breast cancer.
AB  - Elevated and more rapidly increasing breast cancer incidence rates have been
      described for Marin County, California (CA), a homogeneous, high socioeconomic
      status population for which yearly surveillance is facilitated by its status as a
      county. The present study evaluates the histology and hormonal phenotype of the
      excess breast cancer cases occurring in white, non-Hispanic women living in Marin
      County between 1992 and 2000 and compares them with patterns occurring in the
      rest of the San Francisco Bay Area (SFBA) and other urban parts of CA. Incidence
      data for invasive breast cancer histological subtypes and estrogen receptor (ER)
      and progesterone receptor (PR) status were obtained from the 1992-2000
      Surveillance, Epidemiology, and End Results program. Expected numbers for Marin
      County were computed based on age-specific rates for five other SFBA counties.
      Incidence rates were age-adjusted to the 2000 United States standard. Marin
      County breast cancer diagnoses during 1992-2000 compared with other SFBA and
      other urban CA Surveillance, Epidemiology, and End Results county rates for
      white, non-Hispanic women consisted of a disproportionate increase in ER+/PR+
      tumors. The observed absolute excess (versus expected) numbers of Marin County
      ER+/PR+ lobular and nonlobular (predominantly ductal) cases were similar;
      however, the relative increase appeared greatest for lobular breast cancer. The
      progressive increase in breast cancer incidence rates observed in Marin County
      over the past decade is occurring in women with high prevalence of risk factors
      predisposing toward excess development of ER+/PR+ breast cancer.

PMID- 14693748
TI  - The HRAS1 variable number of tandem repeats and risk of breast cancer.
AB  - Rare alleles at the HRAS1 variable number of tandem repeats (VNTRs) locus have
      been implicated in breast cancer risk. We assessed the association of rare HRAS1
      alleles and breast cancer in a case-control study nested within the Nurses'
      Health Study cohort. Using PCR-based methods, 717 incident breast cancer cases
      and 798 controls were genotyped for the HRAS1 VNTRs. The prevalence of the rare
      alleles in breast cancer cases was not different compared with controls (10.7
      versus 12.0%, respectively; P = 0.45, two-sided Cochran-Mantel-Haenzel chi(2)
      test). There was no evidence that women heterozygous (multivariate odds ratio,
      0.97; 95% confidence interval, 0.73-1.27) or homozygous (multivariate odds ratio,
      0.83; 95% confidence interval, 0.32-2.14) for rare alleles were at an increased
      risk of breast cancer or that a positive gene-dose effect existed. The results
      did not vary by menopausal status. Although as a group the rare alleles were not
      associated with breast cancer, one class of rare alleles between the common
      alleles of a3 and a4 was associated with a significantly increased risk. These
      results suggest that there is no overall association between rare alleles of the
      HRAS1 VNTR and breast cancer.

PMID- 14693749
TI  - Serum follicle-stimulating hormone and risk of epithelial ovarian cancer in
      postmenopausal women.
AB  - The "gonadotropin hypothesis" postulates that gonadotropin overstimulation of
      ovarian epithelium results in its increased proliferation and subsequent
      malignant transformation. To address this hypothesis, we assessed the association
      between prediagnostic serum levels of follicle-stimulating hormone (FSH) and the
      risk of epithelial ovarian cancer in postmenopausal women who were part of a case
      control study nested within three prospective cohorts in New York City, Umea,
      Sweden, and Milan, Italy. Case subjects were 88 women with primary invasive
      epithelial ovarian cancer diagnosed between 3 months and 13.1 years after the
      blood donation. Controls were 168 women who were free of cancer and matched the
      case on cohort, age, and enrollment date. Serum FSH was determined using a
      quantitative immunoradiometric assay. FSH concentrations were similar in women
      who subsequently received a diagnosis of epithelial ovarian cancer (median, 44.0
      mIU/ml; range, 13.8-101.2) and in controls (median, 43.4 mIU/ml; range, 13.5
      109.5; P = 0.17). Compared with women in the lowest third, women in the highest
      third of serum FSH were not at increased risk of epithelial ovarian cancer after
      an adjustment for potential confounders (odds ratio, 0.85; 95% confidence
      interval, 0.36-1.99). These observations provide no evidence for an association
      between circulating FSH and risk of epithelial ovarian cancer in postmenopausal
      women and do not appear to support the gonadotropin hypothesis of epithelial
      ovarian carcinogenesis.

PMID- 14693750
TI  - Urinary isothiocyanate excretion, brassica consumption, and gene polymorphisms
      among women living in Shanghai, China.
AB  - Alternative measures of Brassica vegetable consumption (e.g., cabbage) may
      clarify the association between Brassica and cancer risk. Brassica
      isothiocyanates (ITCs) are excreted in urine and may provide a sensitive and food
      specific dietary biomarker. However, the persistence of ITCs in the body may be
      brief and dependent on the activity of several Phase II enzymes, raising
      questions about the relationship between a single ITC measure and habitual
      dietary patterns. This study investigates the association between urinary ITC
      excretion and habitual Brassica consumption, estimated by a food frequency
      questionnaire, among healthy Chinese women enrolled in the Shanghai Breast Cancer
      Study. Participants (n = 347) completed a validated food frequency questionnaire
      querying habitual dietary intake during the prior 5 years and provided a fasting
      first-morning urine specimen. Genetic deletion of glutathione S-transferases
      (GSTM1/GSTT1), and single nucleotide substitutions in GSTP1 (A313G) and
      NAD(P)H:quinone oxidoreductase 1 (NQO1: C609T), were identified from blood DNA.
      Urinary ITC excretion levels were marginally higher with the GSTT1-null or GSTP1
      G/G genotypes (P = 0.07, P = 0.05, respectively). Mean habitual Brassica intake
      was 98.3 g/day, primarily as bok choy, and Brassica intake significantly
      increased across quartile categories of ITC levels. The association between
      habitual Brassica intake and urinary ITC levels was stronger among women with
      GSTT1-null or GSTP1-A/A genotypes, or NQO1 T-allele, and the interaction was
      statistically significant across GSTP1 genotype. In conclusion, a single urinary
      ITC measure, in conjunction with markers of Phase II enzyme activity, provides a
      complementary measure of habitual Brassica intake among Shanghai women.

PMID- 14693751
TI  - Risk of basal cell carcinoma in relation to alcohol intake and smoking.
AB  - We prospectively investigated whether alcohol intake and smoking affect the risk
      of basal cell carcinoma (BCC) in subjects from the United States Radiological
      Technologists (USRT) cohort study. We evaluated 68,371 radiological technologists
      certified during 1926-1982 who were free of cancer at the time they answered a
      first questionnaire (1983-1989) and who completed a second questionnaire (1994
      1998). The first questionnaire provided baseline information on numerous risk
      factors, including smoking and alcohol intake, and the second provided self
      reported cancer diagnoses. During 698,190 person-years of follow-up, we
      identified 1,360 cases of BCC: 1,036 in women and 324 in men. Cox proportional
      hazards regression indicated that the trend in BCC was significantly associated
      with increased alcohol intake (P for trend = 0.001). Compared with those who
      reported no alcohol consumption, those who drank <1-2, 3-6, 7-14, and >14
      drinks/week had multivariate risks of 1.1 [95% confidence interval (CI), 0.9
      1.3], 1.3 (95% CI, 1.1-1.5), 1.4 (95% CI, 1.2-1.7), and 1.0 (95% CI, 0.7-1.6),
      respectively. We found no clear association between smoking and BCC. This is the
      second large prospective study to report a significant but nonmonotonic trend in
      increased risk associated with alcohol consumption.

PMID- 14693752
TI  - Metabolites of a tobacco-specific lung carcinogen in nonsmoking casino patrons.
AB  - Epidemiologic data have shown increased risks of lung cancer in nonsmokers
      exposed to environmental tobacco smoke (ETS). We measured biomarkers in urine
      samples from nonsmokers before and after a 4-h visit to a casino where smoking is
      allowed. The tobacco-specific lung carcinogen, NNK [4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone] is a constituent of ETS. Urinary metabolites of NNK, 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL
      Gluc), are excellent biomarkers of human uptake of NNK and NNAL. NNAL, as with
      NNK, is a potent pulmonary carcinogen. Subjects collected a spot urine sample
      before the casino visit and all urine samples for the 24-h period starting after
      the visit. We analyzed samples for creatinine, total cotinine (cotinine and
      cotinine-glucuronide), and total NNAL (NNAL plus NNAL-Gluc). Paired samples
      showed statistically significant mean increases in total cotinine (0.044 nmol/mg
      creatinine, P < 0.0001) and total NNAL (0.018 pmol/mg creatinine, P < 0.001).
      These findings demonstrate that exposure of nonsmokers to ETS in a commercial
      setting results in uptake of a tobacco-specific lung carcinogen.

PMID- 14693753
TI  - Correspondence re: C. R. Jonas et al., Dietary glycemic index, glycemic load, and
      risk of incident breast cancer in postmenopausal women. Cancer Epidemiol.
      Biomark. Prev., 12: 573-577, 2003.

PMID- 14693757
TI  - Refining the aetiology of myopia through negative results.

PMID- 14693758
TI  - Understanding the molecular genetics of congenital cataract may have wider
      implications for age related cataract.

PMID- 14693759
TI  - Intraocular pressure associations with refractive error and axial length in
      children.
AB  - AIM: To assess whether intraocular pressure (IOP) is associated with refractive
      error or axial length in children. METHODS: Of subjects from the Singapore Cohort
      Study of the Risk Factors for Myopia (SCORM), 636 Chinese children aged 9-11
      years from two elementary schools underwent non-contact tonometry, cycloplegic
      autorefraction, and A-scan biometry during 2001. For analyses, refractive error
      was categorised into four groups; hypermetropia (spherical equivalent refraction
      (SE) > or = +1.0D), emmetropia (-0.5D<SE< +1.0D), low myopia (-3.0D<SE< or = 
      0.5D) and high myopia (SE< or = -3.0D). RESULTS: Of the 636 children examined,
      50.6% were male. The mean IOP was 16.6 (SD 2.7) mm Hg. There were no significant
      IOP differences between low (mean IOP = 16.4 (2.8) mm Hg) or high myopes (16.7
      (2.5) mm Hg) and emmetropes (16.7 (2.9) mm Hg), p = 0.57. IOP was not correlated
      with spherical equivalent refraction (Spearman correlation, r = 0.009) or axial
      length (r = 0.030). In regression analyses adjusting for diastolic blood
      pressure, neither spherical equivalent (regression coefficient = 0.014) nor axial
      length (regression coefficient = 0.027) were significantly associated with IOP.
      CONCLUSION: These findings do not support an association between IOP and
      refractive error or axial length in children. This questions postulated roles of
      IOP in the pathogenesis of myopia.

PMID- 14693760
TI  - Keratometry measurements in preterm and full term newborn infants.
AB  - AIM: To evaluate the relation between postconceptional age and birth weight with
      keratometric values in preterm and full term infants. METHODS: A prospective
      cross sectional study was performed. The cohort included 99 infants (198 eyes)
      admitted to the Neonatal and Neonatal Intensive Care Units at Schneider
      Children's Medical Center of Israel from February to September 2002. Keratometry
      in the horizontal and vertical meridians was performed in both eyes of each
      infant by two ophthalmologists using an autokeratometer. The results were
      evaluated according to: postconceptual age (<32 weeks, 32-36 weeks, >36 weeks)
      and birth weight (<1500 g, 1501-2500 g, >2501 g). RESULTS: Corneal curvature
      measurements decreased progressively with both postconceptual age and birth
      weight. At <32 weeks, mean (standard deviation) readings were 63.3 (3.2) diopters
      (D) for the horizontal meridian and 57.3 (2.6) D for the vertical meridian;
      corresponding values at >36 weeks were 54.0 (3.0) D and 50.7 (2.4) D. In the
      <1500 g group, mean (SD) readings were 61.3 (3.9) D for the horizontal meridian
      and 56.0 (2.9) D for the vertical meridian; corresponding values in the >2501 g
      group were 51.3 (2.1) D and 48.6 (1.8) D. CONCLUSIONS: There is an inverse
      relation of horizontal and vertical keratometric values with both
      postconceptional age and birth weight. Highest readings were noted in the babies
      with the lowest birth weight and youngest postconceptional age. The decrease in
      corneal dioptric power to normal values is linear and is apparently part of the
      normal ocular maturation.

PMID- 14693761
TI  - The usefulness of Vistech and FACT contrast sensitivity charts for cataract and
      refractive surgery outcomes research.
AB  - AIM: To investigate the repeatability and sensitivity of two commonly used sine
      wave patch charts for contrast sensitivity (CS) measurement in cataract and
      refractive surgery outcomes. METHODS: The Vistech CS chart and its descendant,
      the Functional Acuity Contrast Test (FACT), were administered in three
      experiments: (1) Post-LASIK and age matched normal subjects; (2) Preoperative
      cataract surgery and age matched normal subjects; (3) Test-retest repeatability
      data in normal subjects. RESULTS: Contrast sensitivity was similar between post
      LASIK and control groups and between the Vistech and FACT charts. The percentage
      of subjects one month post-LASIK achieving the maximum score across spatial
      frequencies (1.5, 3, 6, 12, 18 cycles per degree) were (50, 33, 13, 13, 0
      respectively) for FACT, but only (0, 0, 13, 4, 0 respectively) for Vistech. A
      small number of cataract patients also registered the maximum score on the FACT,
      but up to 60% did not achieve the minimum score. Test-retest intraclass
      correlation coefficients varied from 0.28 to 0.64 for Vistech and 0.18 to 0.45
      for FACT. Bland-Altman limits of agreement across spatial frequencies were
      between +/-0.30 and +/-0.85 logCS for Vistech, and +/-0.30 to +/-0.75 logCS for
      FACT. DISCUSSION: The Vistech was confirmed as providing poorly repeatable data.
      The FACT chart, likely because of a smaller step size, showed slightly better
      retest agreement. However, the reduced range of scores on the chart due to the
      smaller step size led to ceiling (post-LASIK) and floor (cataract) effects. These
      problems could mask subtle differences between groups of patients with near
      normal visual function as found post-refractive or cataract surgery. The Vistech
      and FACT CS charts are ill suited for refractive or cataract surgery outcomes
      research.

PMID- 14693762
TI  - Mitomycin C as an adjunct in the treatment of localised ocular surface squamous
      neoplasia.
AB  - AIM: To report the outcome of topical mitomycin C (MMC) used as adjunctive
      treatment following primary excision of ocular surface squamous neoplasia (OSSN).
      METHOD: Prospective, non-comparative interventional case series of 27 primary
      OSSN lesions from 26 patients treated in a single ocular oncology centre over a 4
      year period. RESULT: 27 cases of OSSN received a treatment regimen of surgical
      excision, followed by topical MMC. Mean follow up of 27 (SD 12) months (range 12
      50, median 25 months) revealed zero recurrences. CONCLUSION: MMC treatment
      following surgical excision decreases the recurrence rate of primary ocular
      surface neoplasia and should be considered as adjunctive therapy in primary
      treatment.

PMID- 14693763
TI  - LASIK surgery in children.
AB  - AIMS: To report success in the treatment of high myopia in children with LASIK.
      To report the visual results, complications and postoperative management of
      children with high myopia. METHODS: Six children (seven eyes) with high myopia
      were included in this series. Preoperative and postoperative refraction, visual
      acuity, and pachymetry were compared. RESULTS: Six children with high myopia
      ranging from -5.00DS to -16DS were treated. There were three males and three
      females. Five children had improved refraction and visual acuity post-LASIK. Age
      ranged from 2 to 12 years. Five of the children had unilateral amblyopia
      preoperatively. One had bilateral high myopia. CONCLUSION: High myopia in
      children may be treated safely and effectively with LASIK.

PMID- 14693765
TI  - Human corneal stromal tissue concentration after consecutive doses of topically
      applied 3.3% vancomycin.
AB  - AIMS: To evaluate vancomycin penetration into human corneal stromal tissue in
      patients treated with topical vancomycin eyedrops before penetrating keratoplasty
      (PKP). METHODS: Twenty four patients who underwent PKP, seven patients with
      keratoconus (group 1) and 17 patients with corneal scar or corneal decompensation
      (group 2). All patients received topical application of vancomycin eyedrops
      (concentration: 33 mg/ml) 10, 3, 2, 1 hour, and 15 minutes before the operation.
      Corneal cumulative vancomycin levels were assessed by bioassay. RESULTS: Mean
      vancomycin corneal stromal tissue concentration was 46.7 (SE 4.11) microg/g
      tissue. This value was four to 20-fold in excess of the MIC90 of vancomycin in
      Staphylococcus aureus (2-10 microg/ml). CONCLUSIONS: Vancomycin reached high
      corneal tissue concentrations that significantly exceeded the MIC90 (2-10
      microg/ml) for most key Gram positive corneal pathogens. The ratio of vancomycin
      stromal concentration to protein concentration was statistically higher in group
      2 (non-keratoconus).

PMID- 14693766
TI  - The efficacy and safety of topical polymyxin B, neomycin and gramicidin for
      treatment of presumed bacterial corneal ulceration.
AB  - AIM: To evaluate the clinical efficacy and safety of topical polymyxin B,
      neomycin, and gramicidin for the treatment of suspected bacterial corneal
      ulceration at the Leiden University Medical Center. METHODS: Patients with a
      diagnosis of a suspected bacterial corneal ulcer between April 1995 and February
      2002 were retrospectively identified and reviewed; clinical and microbiological
      features and response to therapy were analysed. All patients were treated with
      Polyspectran eye drops. RESULTS: In total, 91 patients were included in this
      analysis. Bacteriological cultures of 46 patients (51%) were positive and
      revealed 51 microorganisms. Staphylococcus aureus (29.4%) and Pseudomonas
      aeruginosa (23.5%) were the most frequently encountered bacteria. Eighteen
      patients switched therapy before complete healing of the corneal ulceration, four
      patients were lost to follow up. Of the 69 patients who completed Polyspectran
      treatment, re-epithelialisation occurred in 68 patients (99%) and on average took
      12.6 (median 8) days. Among 91 patients, there were four perforations and one
      evisceration. Seven toxic or allergic reactions were reported. CONCLUSION: This
      study shows that the combination of polymyxin B, neomycin, and gramicidin is an
      effective and safe treatment of suspected corneal ulceration.

PMID- 14693767
TI  - Risk factors of acute endophthalmitis after cataract extraction: a case-control
      study in Asian eyes.
AB  - AIM: To describe risk factors of acute endophthalmitis after cataract extraction
      in an Asian population. METHODS: A retrospective, case-control study. Cases (n =
      34) were patients with acute endophthalmitis presenting within 6 weeks after
      cataract surgery. Three controls per case (n = 102) were randomly selected from
      the cataract surgery list matched on the date of operation of cases. RESULTS: Few
      risk factors were identified. In multivariable analysis, endophthalmitis was
      associated with silicone intraocular lens (odds ratio 5.1, 95% confidence
      intervals, 1.2 to 21.6, compared to poly(methylmethacrylate) lens) and posterior
      capsular rupture during surgery (odds ratio 20.9, 95% confidence intervals 2.3 to
      187.9). CONCLUSION: Silicone intraocular lens and rupture of the posterior
      capsule are risk factors of acute endophthalmitis after cataract surgery.

PMID- 14693768
TI  - Otago Glaucoma Surgery Outcome Study: long term results of cataract extraction
      combined with Molteno implant insertion or trabeculectomy in primary glaucoma.
AB  - BACKGROUND/AIMS: To describe the long term results of cases of cataract
      extraction combined with either Molteno implant insertion or trabeculectomy for
      primary open angle glaucoma. METHODS: This prospective case series followed cases
      which had cataract extraction and Molteno implant insertion (45 eyes) or
      trabeculectomy (94 eyes) followed up for a mean of 5.3 years and 3.9 years
      respectively. RESULTS: Cataract extraction and Molteno implant insertion or
      trabeculectomy controlled the intraocular pressure at 21 mmHg or less with a
      probability of 1.00 (95% CI 0.93 to 1.00) at 10 years or more after operation and
      0.94 (95% CI 0.89 to 0.99) and 0.73 (95% CI 0.46 to 0.99) at five and 10 years
      after operation respectively. CONCLUSIONS: Cataract extraction combined with
      insertion of Molteno implants or trabeculectomy controlled the intraocular
      pressure in 100% (45/45) and 94% (88/94) of cases respectively.

PMID- 14693769
TI  - Association between posterior uveal melanoma and iris freckles, iris naevi, and
      choroidal naevi.
AB  - AIM: To investigate the association between posterior uveal melanoma and iris
      freckles, iris naevi, and choroidal naevi. METHODS: Cross sectional study of 65
      patients with posterior uveal melanoma and 218 controls. Iris colour, iris
      freckles, iris naevi, and choroidal naevi were recorded for each eye of each
      patient. RESULTS: Iris freckles were present in 40 (61.5%) patients with melanoma
      and 135 (61.9%) controls (p = 0.494). Iris naevi were present in four (6.2%)
      patients with melanoma and nine (4.1%) controls (p = 0.955). Choroidal naevi were
      present in 12 (18.5%) patients with melanoma and 38 (17.4%) controls (p = 0.815).
      CONCLUSION: This study did not detect an association between posterior uveal
      melanoma and iris freckles, iris naevi, or choroidal naevi.

PMID- 14693770
TI  - Association between choroidal pigmentation and posterior uveal melanoma in a
      white population.
AB  - BACKGROUND/AIMS: It is well known that light skin pigmentation is a risk factor
      for cutaneous melanoma. The aim of this study was to investigate the analogous
      association between choroidal pigmentation and posterior uveal melanoma. METHODS:
      Cross sectional study of 65 consecutive patients diagnosed with posterior uveal
      melanoma (melanoma group) and 218 consecutive patients referred for general
      retinal evaluation (control group). All patients were white. A clinical grading
      system for estimating choroidal pigmentation was developed and histologically
      validated in seven patients. RESULTS: Melanoma patients with light iris colour
      were significantly more likely to have darker choroidal pigmentation than
      controls (p = 0.005). Darker choroidal pigmentation was associated histologically
      with increased density of choroidal melanocytes (p = 0.005). CONCLUSIONS:
      Increased choroidal pigmentation, as a result of an increase in the density of
      pigmented choroidal melanocytes, is not protective but may actually be a risk
      factor for the development of posterior uveal melanoma in white patients. This
      finding may have implications for understanding the pathogenesis of uveal
      melanoma.

PMID- 14693771
TI  - Inhibition of experimental diabetic cataract by topical administration of RS
      verapamil hydrochloride.
AB  - AIM: To investigate the efficacy of verapamil eye drops for inhibition of
      diabetic cataract in rats. METHODS: Diabetes was induced in 69 male Sprague
      Dawley rats by an intraperitoneal injection of streptozotocin (65 mg/kg body
      weight). One group (DV) of animals was treated by instillation of one drop of
      0.2% RS-verapamil hydrochloride in both eyes three times daily for 8 weeks. The
      placebo treated group (D) received the vehicle solution only. After 8 weeks the
      lenses were removed, inspected, and photographed using bright and dark field
      illumination. The transmission of He-Ne laser light was measured in the optical
      axis of each lens in order to determine the turbidity coefficient (t) as a
      measure of central lens opacity. Following digital image analysis, the integrated
      density as a measure of central and mid-peripheral opacities was determined.
      RESULTS: Lenses of both groups developed peripheral cortical opacities not
      affecting the optical axis. Advanced and paracentral cortical opacities were
      present in 10 (16.7%) of the placebo treated lenses (D) and two (3.8%) of the
      verapamil treated lenses (DV). Complete corticonuclear cataract developed in four
      (6.7%) of the lenses from group D but none of the lenses from group DV. The mean
      lens turbidity t was determined to be 0.019 (SEM 0.002) mm(-1) (n = 52) in the
      verapamil treated diabetic rats (DV) and 0.042 (0.008) mm(-1) (n = 60) in the
      placebo treated group (D). This difference was statistically significant (p =
      0.0054). The mean integrated density was 274.91 (22.5) in group D (n = 60) and
      196.28 (20.7) in group DV (n = 37). This difference was also significant (p =
      0.0037). CONCLUSION: Verapamil eye drops 0.2% administered three times daily are
      effective in inhibiting the progression of lens opacities in streptozotocin
      diabetic rats.

PMID- 14693772
TI  - Bioavailability of fluorescein from a new drug delivery system in human eyes.
AB  - AIM: To assess the ocular bioavailability of fluorescein from a novel drug
      delivery system compared with one single preservative free eye drop. METHODS:
      Part A: In a randomised study 10 volunteers applied the lyophilisate to one eye
      and a conventional fluorescein eye drop to the fellow eye. Fluorophotometry was
      performed before and every 2 minutes up to 30 minutes after application in the
      cornea and anterior chamber. Part B: Another 10 volunteers applied each form of
      the application. Fluorophotometry was performed before, +2 minutes, and at +8,
      +10, +12 hours. The dose corresponding to a single fluorescein dose of the
      lyophilisate was 68 l microg fluorescein SE 0.17%. RESULTS: Part A: During the
      first 30 minutes after administration of the preservative free eye drop of 40
      microg the corneal and anterior chamber concentration means were up to 16 times
      higher in eyes treated with the lyophilisate. Part B: 8-12 hours after
      application the mean fluorescein concentration in the cornea of the lyophilisate
      group was two times higher than at baseline. Eyes treated with eye drops had
      baseline values at +8, +10 and +12 hours. CONCLUSION: A significantly better
      bioavailability was achieved in human eyes by using lyophilisate compared with
      the same dose from a conventional eye drop. Lyophilisates are a favourable
      alternative to conventional eye drops since they have no preservatives, higher
      long term stability, no pH adjustment, and easy handling.

PMID- 14693773
TI  - Flicker observation light induces diameter response in retinal arterioles: a
      clinical methodological study.
AB  - AIM: To investigate diameter changes in retinal arterioles in response to flicker
      variations of the examination light. METHODS: One randomised eye of five healthy
      subjects (mean age 33.8 (SD 1.6) years) was examined. The arterial diameter
      response to flicker light (12.5 Hz, 530-600 nm, duration 20 seconds) was
      automatically and continuously measured online three times by retinal vessel
      analyser (RVA) and once offline from flash images using the VesselMap program.
      RESULTS: An arterial diameter response to flicker light was found both by RVA and
      by analysis of flash images (p<0.001). The maximum induced dilation reached at
      the end of the flicker period was +7.4% (SD 2.4%) in the RVA measurements and
      +3.5% (0.8%) in the photographs (p = 0.01). In both techniques the vascular
      diameter overshot the baseline approximately 10 seconds. In the RVA measurements
      a minimum of -4.6% (1.9%) (p = 0.01) was measured 22 (4.7) seconds after the end
      of flicker exposure. CONCLUSION: Flicker evoked response for retinal arterioles
      was found both by RVA and by analysis of flash images. The authors believe that
      the method is suitable for the quantitative investigation of retinal
      vasosclerosis, especially in association with arteriosclerotic and hypertensive
      systemic disease.

PMID- 14693774
TI  - Variation associated with measurement of retinal vessel diameters at different
      points in the pulse cycle.
AB  - BACKGROUND/AIMS: To assess the variability in retinal vessel measurements at
      different points in the pulse cycle. METHODS: A healthy white male aged 19 years
      had 30 digitised images taken at three distinct points in the pulse cycle over a
      one hour period. A pulse synchronised ear clip trigger device was used to capture
      images at the desired point in the pulse cycle. Two trained graders measured the
      retinal vessel diameter of one large arteriole, one large venule, one small
      arteriole, and one small venule 10 times in each of these 30 images. RESULTS:
      Within an image, variability was similar between graders, pulse point, and vessel
      type. Across images taken at the same point in the pulse period, the change from
      the minimum to maximum measurement was between 6% and 17% for arterioles and
      between 2% and 11% for venules. In addition, measurements of small vessels had
      greater changes than large vessels and no point in the pulse period was more
      variable than another. Ignoring pulse cycle increased variability across images
      in the large venule, but not in the other vessel types. Mixed effect models were
      fit for each of the vessel types to determine the greatest source of variability.
      Controlling for pulse point and grader, the largest source of variability for all
      four vessels measured was across images, accounting for more than 50% of the
      total variability. CONCLUSION: Measurements of large retinal venules is generally
      less variable than measurements of other retinal vessels. After controlling for
      pulse point and grader, the largest source of variation is across images.
      Understanding the components of variability in measuring retinal vessels is
      important as these techniques are applied in epidemiological studies.

PMID- 14693775
TI  - Eccentricity and measurement variability and repeatability with the retinal
      thickness analyser.
AB  - AIMS: To define the variability and repeatability of retinal thickness
      measurements using the retinal thickness analyser (RTA) and to elucidate any
      interaction between eccentricity (that is, position relative to the fovea) and
      variability and repeatability. METHODS: The sample comprised 20 normal subjects
      of mean age 33 years. Each subject attended for two visits. Repeated RTA scans
      were acquired centred on the fovea and for any one of the four possible non
      foveal scan areas. The mean retinal thickness (+SD) was calculated for a series
      of concentric circular bands centred on fixation. A repeated measures analysis of
      variance (ANOVA) was used to determine any significant interaction between the
      variability of RTA thickness values and eccentricity. RESULTS: The group mean
      coefficient of variation and coefficient of repeatability were highest at the
      fovea. The repeated measures ANOVA revealed that the within test variability of
      RTA measurements varied significantly with eccentricity (p<0.0001). Similarly,
      the between test repeatability varied significantly with eccentricity (p =
      0.045). CONCLUSION: The significantly elevated within test variability and
      between test repeatability in the foveal area need to be considered when using
      the RTA to evaluate patients with macular disease.

PMID- 14693776
TI  - Cyclic esotropia and the treatment of over-elevation in adduction and V-pattern.
AB  - AIM: To describe the development and treatment of V-pattern and bilateral over
      elevation in adduction in patients with cyclic esotropia. METHODS: Three patients
      with cyclic esotropia are described in retrospect. All patients underwent
      bilateral medial recession, while one patient additionally had a weakening
      procedure of both inferior oblique muscles. RESULTS: All patients developed a V
      pattern and bilateral over-elevation in adduction. After strabismus surgery,
      normal eye alignment with some signs of binocularity was reached in all three
      patients. Moreover, the over-elevation in adduction and V-pattern completely
      resolved. CONCLUSIONS: V-pattern and bilateral over-elevation in adduction was
      seen in all patients with cyclic esotropia in the stage that fusion was
      disrupted. Possible explanations for the origin of these patterns are discussed.
      Strabismus surgery aimed to correct the horizontal esotropic angle restored
      fusion and eliminated the vertical incommitancies in lateral gaze, and the V
      pattern.

PMID- 14693777
TI  - Serious eye injuries caused by bottles containing carbonated drinks.
AB  - AIM: To analyse serious eye injuries caused by bottles containing pressurised
      drinks. METHODS: Retrospective review of the databases of US, Hungarian, and
      Mexican eye injury registries. RESULTS: In the combined database (12 889
      injuries), 90 cases (0.7%) were caused by bottle tops or glass splinters. The
      incidence varied widely: 0.3% (United States), 3.1% (Hungary), and 0.9% (Mexico),
      as did the agent. Champagne bottle corks were responsible in 20% (United States),
      71% (Hungary; p<0.0001), and 0% (Mexico). Most eyes improved, but 26% remained
      legally blind. CONCLUSIONS: The presence of warning labels on champagne bottles
      appears to reduce cork related eye injuries, as does using plastic bottles and
      caps.

PMID- 14693778
TI  - The relation of Graves' ophthalmopathy to circulating thyroid hormone status.
AB  - AIM: The risk factors and epidemiological data for Graves' ophthalmopathy with
      and without abnormal circulating thyroid levels were examined to determine the
      relation of thyroid dysfunction to ophthalmopathy. METHODS: The authors
      retrospectively evaluated 482 patients seen with Graves' ophthalmopathy. Of
      these, 413 were classified as having abnormal levels of circulating thyroid
      hormone (ALTH) and 69 as having normal levels of circulating thyroid hormone
      (NLTH). RESULTS: Patients in the NLTH group, compared to the ALTH group, were
      older on average (56 (SD 13.5) v 52 (15.4)) and had a higher age adjusted body
      mass index (26.1 (0.8) v 23.4 (0.3)). In addition, a higher percentage of NLTH
      patients had hypercholesterolaemia. Those in the ALTH group were more likely to
      be female (76% v 51%), to have a family history of thyroid problems, and to have
      had eye surgery. CONCLUSION: NLTH and ALTH appear to differ from each other in
      terms of risk factors and epidemiological characteristics. Additionally, thyroid
      dysfunction seems to be associated with a more severe ophthalmopathy compared to
      the euthyroid state.

PMID- 14693779
TI  - Assessing quality of life in Australian patients with Graves' ophthalmopathy.
AB  - AIMS: To determine quality of life and adequacy of education and counselling in
      Australian patients with Graves' ophthalmopathy during the course of their
      illness. METHODS: A cross sectional study was conducted at the orbital and
      endocrinology clinics of Royal Brisbane Hospital on 162 consecutive patients with
      Graves' ophthalmopathy who were managed between the 1992 and 2000. The Graves'
      ophthalmopathy quality of life (GO-QOL) survey modified for Australian conditions
      was distributed to study participants. Of the 19 questions asked, nine questions
      related to visual functioning, eight questions were about the psychosocial
      consequences of changed appearance, and two questions referred to education and
      counselling. Additionally, clinical data on the severity of illness were
      collected retrospectively from the medical notes of these patients. RESULTS:
      Completed questionnaires were received from 128 patients. The majority of
      patients reported limitations in daily activities such as hobbies, driving,
      watching television and reading, as well as impaired self confidence. The mean GO
      QOL scores in this study were (100 representing maximum QOL): visual functioning
      59.0 (SD 28.0), psychosocial consequences of changed appearance 54.5 (28.4), and
      education and counselling 59.1 (38.8). Only about a quarter of patients indicated
      that education and counselling were adequate and helpful. CONCLUSION: Graves'
      ophthalmopathy profoundly affects QOL and adequate education and counselling are
      essential for helping patients to cope with their illness. The GO-QOL survey is a
      simple, practical tool that can be used easily in a clinic to determine the QOL
      issues in subjects with Graves' ophthalmopathy.

PMID- 14693780
TI  - Investigation of crystallin genes in familial cataract, and report of two disease
      associated mutations.
AB  - AIMS: Mutations of seven crystallin genes have been shown to cause familial
      cataract. The authors aimed to identify disease causing crystallin mutations in
      paediatric cataract families from south eastern Australia. METHODS: 38 families
      with autosomal dominant or recessive paediatric cataract were examined. Three
      large families were studied by linkage analysis. Candidate genes at regions
      providing significant LOD scores were sequenced. Single stranded conformational
      polymorphism (SSCP) analysis was used to screen five crystallin genes in the
      probands, followed by direct sequencing of observed electrophoretic shifts.
      Mutations predicted to affect the coding sequence were subsequently investigated
      in the entire pedigree. RESULTS: A LOD score of 3.72 was obtained at the gamma
      crystallin locus in one pedigree. Sequencing revealed a P23T mutation of CRYGD,
      found to segregate with disease. A splice site mutation at the first base of
      intron 3 of the CRYBA1/A3 gene segregating with disease was identified by SSCP in
      another large family. Five polymorphisms were also detected. CONCLUSIONS:
      Although mutations in the five crystallin genes comprehensively screened in this
      study account for 38% of paediatric cataract mutations in the literature, only
      two causative mutations were detected in 38 pedigrees, suggesting that crystallin
      mutations are a relatively rare cause of the cataract phenotype in this
      population.

PMID- 14693781
TI  - Tissue crossmatch before corneal transplantation.
AB  - AIM: To investigate the influence of anticorneal antibodies on the outcome of
      transplantation in recipients before penetrating keratoplasty. METHODS: 100
      consecutive penetrating keratoplasties performed between July 1995 and June 1996
      were included in this study. Donor corneoscleral rim cryosections were incubated
      with recipient serum. Fixation of recipient IgM on donor corneas was revealed
      with a polyclonal anti-human mu-chain antibody. The mean follow up time was 61
      months. Five years after transplantation, 63% of patients were available for
      follow up. During the follow up period, 15% of keratoplasties failed because of
      irreversible rejection. RESULTS: Anti-donor stromal lamellae IgM were found in 14
      recipients. Anti-donor keratocyte IgM were present in 28 recipients. Dilution of
      recipient serum (up to 1/800) did not modify the results of positive crossmatch
      assays. Crossmatch assays performed with positive recipient sera and negative
      donor corneoscleral rims were negative. No significant influence of IgM
      crossmatch results on graft survival and rejection-free graft survival was found.
      CONCLUSION: Donor specific anticorneal stroma IgM were found in 28% of recipients
      before transplantation. This pre-immunisation was not associated with a higher
      risk of transplantation rejection.

PMID- 14693782
TI  - Randomised controlled trial comparing the effect of brimonidine and timolol on
      visual field loss after acute primary angle closure.
AB  - AIM: To compare the effect of brimonidine and timolol in reducing visual field
      loss in patients with acute primary angle closure (APAC). METHODS: In addition to
      standard acute medical treatment, patients presenting with APAC were randomised
      to either brimonidine 0.2% or timolol 0.5% upon diagnosis, then twice daily for 4
      weeks. After laser peripheral iridotomy (LPI), subjects underwent three baseline
      perimetry tests during the first week, and then at weeks 4, 8, 12, and 16.
      Pointwise linear regression analysis was applied to the field series of each of
      these subjects starting with the third test (total of five tests per subject).
      Progression was defined as a significant regression slope (p<0.05) showing 1 dB
      per year or more of sensitivity loss at the same test location in the series.
      Patients were also compared for prevalence of abnormal fields at 16 weeks, which
      was defined as an abnormal glaucoma hemifield test result and/or corrected
      pattern standard deviation outside the 95% confidence limits. RESULTS: 59
      subjects (31 in the brimonidine group; 28 in the timolol group) completed the
      study. There were 47 females (79.7%), the majority of subjects (94.9%) were
      Chinese and the mean age was 59.2 (SD 7.2) years. There were no significant
      differences between the two groups with respect to demographic features,
      presenting intraocular pressure (IOP), duration of symptoms, time from
      presentation to LPI, or mean IOP at each study visit. Over the 16 week study
      period, despite adequate statistical power, no difference was found between
      groups in terms of the number of patients with progressing locations, the mean
      number of progressing locations per subject, or the mean slope of the progressing
      locations. Nine (29%) subjects in the brimonidine group and 10 (35.7%) in the
      timolol group were found to have significant visual field defects at 16 weeks (p
      = 0.58). 15 out of these 19 subjects (78.9%) already had these visual field
      defects in the first week. CONCLUSIONS: In the first 16 weeks after APAC, there
      was no difference in the prevalence of visual field defects or rate of visual
      field progression between brimonidine and timolol treated groups.

PMID- 14693783
TI  - Comparative study between deep sclerectomy with and without collagen implant:
      long term follow up.
AB  - AIM: To identify the value of using collagen implant in deep sclerectomy.
      METHODS: A prospective randomised trial of 104 eyes (104 patients) with medically
      uncontrolled primary and secondary open angle glaucoma. All patients had deep
      sclerectomy (DS), half of them with and the other half without a collagen implant
      (CI) sutured in the scleral bed. The main outcome measures were intraocular
      pressure (IOP), visual acuity, number of treatments preoperative and
      postoperative, and Nd:YAG goniopunctures. RESULTS: Mean follow up period was 44.5
      (SD 21) months for the DS group and 43.9 (SD 14) months for the deep sclerectomy
      with a collagen implant (DSCI) group. The mean preoperative IOP was 23.3 (SD 7.2)
      mm Hg for the DS group and 25.6 (SD 4.9) mm Hg for the DSCI group. The mean IOP
      at the first postoperative day was 6.1 (SD 4.21) mm Hg for the DS group and 5.1
      (SD 3.3) mm Hg for the DSCI group. At 48 months IOP was reduced by 40% (14 versus
      23.3 mm Hg) for the DS group and by 50% (12.7 versus 25.6 mm Hg) for the DSCI
      group. Complete success rate, defined as IOP lower than 21 mm Hg without
      medication, was 34.6% (18/52 patients) at 48 months for the DS group, and 63.4%
      (33/52 patients) for the DSCI group. Qualified success rate; patients who
      achieved IOP below 21 mm Hg with or without medication, was 78.8% (41/52
      patients) at 48 months and 94% (49/52 patients) for the DSCI group. The mean
      number of medications was reduced from 2.1 (SD 0.8) to 1.0 (SD 1) after DS, and
      was reduced from 2.2 (SD 0.7) to 0.4 (SD 0.6) in the DSCI group (p = 0.001)
      CONCLUSION: The use of a collagen implant in DS enhances the success rates and
      lowers the need for postoperative medication.

PMID- 14693784
TI  - Outcomes of bleb excision and conjunctival advancement for leaking or hypotonous
      eyes after glaucoma filtering surgery.
AB  - AIM: To determine outcomes of bleb excision and conjunctival advancement for
      leaking or hypotonous eyes after glaucoma filtering surgery. METHODS: In a
      retrospective case series the medical records of all patients who underwent bleb
      excision and conjunctival advancement surgery for bleb leaks or hypotony (defined
      as IOP less than 6 mm Hg, associated with reduced vision) at the Jules Stein Eye
      Institute and the Yale University Eye Center between January 1993 and June 2002
      were reviewed. Only patients with more than 6 months of follow up were included.
      Complete success was defined as resolution of the pre-existing leak or hypotony,
      with maintenance of IOP > or =6 and < or =21 mm Hg, in the absence of further
      glaucoma surgery and without any glaucoma medication. Qualified success met the
      above criteria with or without the use of glaucoma medications. Success rates
      were analysed with Kaplan-Meier survival curves. RESULTS: 49 eyes were included
      in the study; 13 eyes had overt bleb leaks, 27 eyes had hypotony. Nineteen
      patients underwent resuturing of sclera and/or placement of a pericardial graft
      in addition to bleb excision and conjunctival advancement. Mean preoperative IOP
      increased from 3.2 (SD 2.4) mm Hg (range 0-10 mm Hg) to 13.8 (4.8) mm Hg (range 6
      29 mm Hg) at last follow up (p<0.0001). Mean preoperative visual acuity improved
      from 0.6 (0.3) logMAR (range 0-2) to 0.3 (0.3) logMAR (range 0-2) at final follow
      up (p<0.0001). 16 eyes (40%) were classified as complete success and 17
      additional eyes achieved qualified success, for a total of 33 eyes (83%)
      achieving at least qualified success. There was no significant difference in the
      rate of complete success (p = 0.95) or qualified success (p = 0.88) between the
      group of patients who underwent bleb excision and conjunctival advancement alone
      versus those who also had resuturing of sclera and/or placement of a pericardial
      graft. Failures included three eyes that had persistent hypotony without leak,
      requiring additional bleb revision, and four with uncontrolled IOP, two of whom
      underwent additional glaucoma surgery. CONCLUSION: Bleb excision with
      conjunctival advancement is a successful procedure for bleb repair. This
      technique provides successful resolution of leaks and hypotony, maintains
      glaucoma control with or without medication, and preserves vision with minimal
      postoperative complications in a majority of eyes.

PMID- 14693785
TI  - Retinal vessel wall signs and the 5 year incidence of age related maculopathy:
      the Blue Mountains Eye Study.
AB  - AIMS: To assess whether retinal arteriolar wall changes (focal narrowing and
      arteriovenous nicking) are associated with an increased 5 year risk of age
      related maculopathy (ARM). METHODS: The Blue Mountains Eye Study examined 3654
      residents aged 49+ years living in a defined area, during 1992-4 (82.4%
      participation). After 5 years, 2335 surviving participants (75.1%) were re
      examined during 1997-9. Retinal photographs were graded using the Wisconsin ARM
      grading system. Incident late (neovascular or atrophic) or early stage ARM was
      defined using a side by side grading method. Focal arteriolar narrowing
      (localised constricted arteriolar segments causing a sausage-like appearance),
      and arteriovenous (AV) nicking (constriction on both sides of the venule where
      crossed by an arteriole), were graded by comparison with standard photographs.
      All retinal vessels passing through a circumferential zone 0.5-1.0 disc diameters
      from the optic disc margin were measured from digitised images. Summarised
      estimates for central retinal arteriolar equivalent (CRAE) represent an average
      diameter of arterioles for that eye. Associations were assessed after adjusting
      for age, sex, smoking, mean arterial blood pressure, and other vascular risk
      factors. RESULTS: Of 2314 baseline participants at risk of late stage ARM, either
      late stage lesion developed in 34 participants (1.5%). Of 2203 at risk of early
      stage ARM, this sign developed in 197 participants (8.9%). Focal arteriolar
      narrowing was present at baseline in at least one eye of 162 survivors (6.9%) and
      severe AV nicking was present in 187 people (8.1%). Over 5 years, 4.9% of
      subjects with and 1.2% of those without focal narrowing developed either late
      stage ARM lesion, age adjusted relative risk (RR) 2.3, 95% confidence interval
      (CI) 1.0 to 5.1, multivariate adjusted odds ratios (OR) 2.1 (95% CI 0.9 to 4.9).
      Similarly, 3.7% of subjects with and 1.3% of those without severe AV nicking
      developed late ARM lesions, age adjusted RR 2.1 (95% CI 0.9 to 5.1), multivariate
      adjusted OR 2.2 (95% CI 0.9 to 5.6). Corresponding age adjusted RR and
      multivariate adjusted OR for development of early stage ARM were 1.4 (95% CI 0.9
      to 2.0) and 1.3 (95% CI 0.8 to 2.1) for focal arteriolar narrowing, and 1.6 (95%
      CI 1.0 to 2.3) and 1.8 (95% CI 1.1 to 2.9) for severe AV nicking, respectively.
      No associations between baseline CRAE and 5 year incident late or early stage ARM
      were found. CONCLUSIONS: Although of borderline statistical significance, the
      consistent associations found in this study suggest that structural retinal
      arteriolar changes may either contribute to ARM progression or may share common
      pathological pathways with ARM.

PMID- 14693786
TI  - Autologous peripheral retinal pigment epithelium translocation in patients with
      subfoveal neovascular membranes.
AB  - AIM: To evaluate the possibility of translocating autologous peripheral retinal
      pigment epithelial (RPE) cells and enhance their adhesion to improve functional
      outcome after choroidal neovascular membrane extraction in patients with
      subfoveal neovascular membranes. METHODS: A prospective, non-controlled surgical
      study in eight consecutive patients operated between February and July 2001 with
      final data monitoring in July 2002. All patients had mixed subfoveal membranes of
      2-4 disc diameters. Functional tests included Snellen vision and central fixation
      testing. During vitrectomy, after the extraction of the neovascular complex, 8 x
      10(4)-16 x 10(4) RPE cells were removed from the periphery and translocated under
      the macula following the submacular injection of 2 microg of poly-L-lysine to
      promote adhesion of the cells. RESULTS: With a follow up ranging from 3 months to
      16 months, a pigmented area was seen in the extraction bed of the neovascular
      membrane in only one patient. Fixation was at the edge of the extraction bed in
      three patients. Vision remained the same in five patients and deteriorated in
      three (all with retinal detachment). Retinal detachment due to proliferative
      vitreoretinopathy occurred in three patients. CONCLUSIONS: The translocation of
      autologous peripheral RPE cells after membrane extraction was technically
      possible in a sterile manner, but was associated with a high proliferative
      vitreoretinopathy rate and in the present series had no measurable positive
      effect on functional outcome.

PMID- 14693787
TI  - Radiotherapy for recurrent choroidal neovascularisation complicating age related
      macular degeneration.
AB  - AIMS: To report the safety and visual outcome data of external beam irradiation
      for recurrent choroidal neovascularisation complicating age related macular
      degeneration. METHODS: Eighteen consecutive eyes received external beam
      irradiation with seven fractions of 2 Gy (total dose 14 Gy). The next 16
      consecutive eyes received external beam irradiation with five fractions of 3 Gy
      (total dose 15 Gy). Main outcome measure was change in visual acuity. Secondary
      outcome variables were contrast sensitivity and fundus photographic/fluorescein
      angiographic progression. RESULTS: The 3 Gy fraction group lost fewer lines of
      distance visual acuity at the three and six month follow up. At one year follow
      up, this difference was not maintained with 2 Gy fraction and 3 Gy fraction eyes.
      At one year follow up a decrease in visual acuity of three or more lines
      (moderate visual loss) occurred in 58% of 2 Gy and 42% of 3 Gy fraction eyes
      (p<0.36). At one year follow up a decrease in visual acuity of six or more lines
      (severe visual loss) occurred in 41% of 2 Gy eyes and 17% of 3 Gy eyes (p<0.23).
      At three months follow up, 3 Gy eyes were less likely (0%) than 2 Gy eyes (47%)
      to show moderate visual loss (p<0.003). However, Kaplan Meier curves estimate a
      significantly lower rate of severe visual loss in the 3 Gy group (p = 0.02).
      There were no significant differences in contrast sensitivity loss or fluorescein
      angiographic stabilisation rates. No evidence of radiation toxicity was observed.
      CONCLUSION: Our results are consistent with trends for a palliative benefit with
      higher fraction sizes and doses. The radiobiologic differences between low and
      high fraction size groups in this study are modest and correlate with the modest
      and short term difference in visual outcomes. These trends support further
      investigation of radiotherapy using fraction sizes of 4 Gy or higher.

PMID- 14693788
TI  - Secondary retinal changes associated with choroidal naevi and melanomas
      documented by optical coherence tomography.
AB  - AIMS: To establish the characteristics of secondary retinal changes associated
      with the presence of choroidal melanomas and choroidal naevi as documented by
      optical coherence tomography (OCT). METHODS: Twenty patients with untreated
      choroidal melanoma and 40 patients with presumed choroidal naevi managed by
      regular observation were included in the study. OCT scans across the surface of
      the tumour and surrounding tissue were acquired for all participants. The
      appearance of retinal tissue on the OCT scans was considered to be abnormal if it
      did not display the well defined band structure characteristic of normal tissue
      on OCT scans. RESULTS: Serous retinal detachments were observed in all patients
      with choroidal melanoma and 18 out of 20 also had abnormal retinal structure or
      intra-retinal splitting in the tissue overlying the tumour. Out of the 40
      patients with presumed choroidal naevi, 12 had serous detachments and three had
      either abnormal retinal structure or intra-retinal splitting overlying the
      lesion. CONCLUSIONS: Secondary retinal changes associated with choroidal lesions
      can be documented by OCT. These changes were observed in most patients with
      choroidal melanoma included in the study group but were far less prevalent in the
      patients with presumed choroidal naevi. OCT is also able to identify the presence
      of small serous detachments before they become clinically visible. Follow up of
      these patients is required to determine whether the OCT results may be of use in
      the differential diagnosis of small choroidal lesions.

PMID- 14693789
TI  - Short wavelength automated perimetry and tamoxifen use.
AB  - BACKGROUND/AIMS: Oestrogen receptors (ORs) have been reported to be present in
      the retina, and the selective oestrogen receptor modulator tamoxifen has been
      reported to affect colour vision. This study aimed, therefore, to determine
      whether standard doses of tamoxifen affect visual sensitivities mediated via
      short wavelength sensitive (SWS) cones. METHODS: Two types of visual fields were
      measured for middle aged women who were being treated with 20 mg of tamoxifen
      daily as adjuvant therapy for early stage breast cancer. Visual fields were
      measured using short wavelength automated perimetry (SWAP) and frequency doubling
      perimetry (FDP). For SWAP, 24-2 visual fields were analysed. No subjects had
      tamoxifen retinopathy or other eye disease. For each type of visual field, mean
      deviations (MDs) were assessed as a function of the duration of tamoxifen use,
      using a cross sectional design. In addition, the difference between the two types
      of MDs was computed after standardisation of each type of MD separately, and this
      difference itself was evaluated as a function of the duration of tamoxifen use.
      Duration dependent changes for SWAP were further evaluated as a function of
      eccentricity within the visual field, and the visual field data were compared
      with foveal data obtained psychophysically. RESULTS: SWAP sensitivities depended
      on the duration of tamoxifen use. Subjects who used tamoxifen for about 2 years
      or less were significantly more likely than subjects who had longer use to have
      high MDs. The difference between the standardised SWAP and FDP MDs likewise was
      significantly related to the duration of use, whereas duration of use effects for
      FDP itself were reduced or absent. Although the duration of use effect observed
      for SWAP was strongest in the peripheral portion of the visual field, there was
      evidence of changes in SWS cone mediated vision even at the fovea. CONCLUSION:
      Standard dosages of tamoxifen can affect SWAP visual fields. The effects of
      tamoxifen are not equivalent for SWAP and FDP, indicating that tamoxifen affects
      some types of visual pathways preferentially or selectively. SWS cone pathways,
      in particular, are affected. SWAP appears able to reveal effects of tamoxifen
      occurring years before completion of the standard 5 year regimen of use.

PMID- 14693791
TI  - The treatment of acute dacryocystitis using laser assisted endonasal
      dacryocystorhinostomy.
AB  - AIMS: To determine whether acute dacryocystitis complicated by abscess formation
      can be successfully treated using laser assisted endonasal dacryocystorhinostomy.
      METHODS: A protocol was adopted for the management of acute dacryocystitis
      presenting to an ophthalmology department. All patients were assessed jointly by
      an ophthalmologist and otolaryngologist for their suitability for primary
      internal drainage via a nasal endoscopic approach. All suitable patients during
      the study period August 1999 to November 2000 were managed by intravenous
      antibiotics and holmium:YAG laser dacryocystorhinostomy. RESULTS: Nine patients
      were studied (mean age 72 years (range 38-82 years), three men, six women). A
      history of chronic epiphora was found in 78% of patients, and recurrent
      nasolacrimal infections in the same 78%. Resolution of symptoms and signs of
      acute dacryocystitis occurred in all nine patients. No recurrence of acute
      dacryocystitis occurred during the median follow up period of 11 months (range 6
      31 months). Ostium patency defined as the absence of epiphora and the observation
      of irrigated lacrimal fluorescein at the ostium was achieved in 67% of patients.
      Epiphora recurred in 33% of cases. CONCLUSION: Laser assisted endonasal
      dacryocystorhinostomy is an effective primary treatment in cases of acute
      dacryocystitis complicated by abscess formation. In addition, pre-existing
      symptoms of epiphora and recurrent nasolacrimal infections are relieved in the
      majority of patients.

PMID- 14693790
TI  - A simplified approach to the treatment of Duane's syndrome.
AB  - INTRODUCTION: To report the results of a large series of patients undergoing
      treatment for Duane's syndrome. METHODS: Patients with Duane's syndrome
      undergoing strabismus surgery of a horizontal muscle recession procedure, medial
      rectus recession for an esodeviation or lateral rectus recession for an
      exodeviation, in order to correct an abnormal head position (AHP) and a
      significant tropia in primary position were identified. Amount of recession
      varied with the angle of deviation in forced primary position, versions and
      ductions, and intraoperative forced ductions. Elimination of AHP was used as a
      criterion for success. RESULTS: Fifty nine patients were treated with either
      unilateral or bilateral medial or lateral rectus recession. Mean follow up was
      3.1 years. Ninety three percent achieved a postoperative alignment of < or =15
      degrees AHP, 66% achieved < or =5 degrees AHP. Only three patients, two from the
      unilateral Type II group and one from the bilateral combined Types I and II
      group, went on to have a second procedure for a noticeable residual AHP.
      CONCLUSIONS: Success (good to excellent results) of horizontal muscle recession
      was achieved in 93% of patients. Unilateral or bilateral horizontal rectus muscle
      recession offers a simple and effective surgical option for eliminating AHP and
      is our treatment of choice in patients with Duane's syndrome.

PMID- 14693792
TI  - Diagnosis of herpes simplex virus-1 keratitis using Giemsa stain,
      immunofluorescence assay, and polymerase chain reaction assay on corneal
      scrapings.
AB  - AIMS: To evaluate three tests used routinely for the diagnosis of herpes simplex
      virus (HSV) keratitis. METHODS: Corneal scrapings from 28 patients with
      clinically typical dendritic corneal ulcer suggestive of HSV keratitis, and 30
      patients with clinically non-viral corneal ulcers, were tested by (i) Giemsa
      stain for multinucleated giant cells, (ii) immunofluorescence assay (IFA) for HSV
      1 antigen, and (iii) polymerase chain reaction (PCR) for HSV-1 DNA, by
      investigators masked to clinical diagnosis. The control subjects were also
      investigated by smears and cultures for bacteria, fungus, and Acanthamoeba.
      RESULTS: The specificity and positive predictive values of all three tests for
      the diagnosis of HSV keratitis were between 95-100%. The sensitivity of IFA and
      PCR was 78.6% and 81.2%, respectively, and the difference was not significant;
      however, their sensitivity and negative predictive value were significantly
      higher than Giemsa stain. CONCLUSIONS: While a combination of IFA and PCR
      constitute the choice of tests in clinically suspected cases of HSV keratitis,
      multinucleated giant cells in Giemsa stain can pre-empt testing by IFA and PCR in
      otherwise atypical cases of HSV keratitis.

PMID- 14693794
TI  - Epithelial downgrowth following clear cornea phacoemulsification in a buphthalmic
      eye.

PMID- 14693793
TI  - Protein kinase C inhibition and diabetic retinopathy: a shot in the dark at
      translational research.
AB  - TRANSLATIONAL RESEARCH IN PRACTICE: a PKC-beta inhibitor for diabetic retinopathy

PMID- 14693795
TI  - Posterior uveal effusion syndrome after trabeculectomy in an eye with ocular
      venous congestion.

PMID- 14693796
TI  - Intravitreal triamcinolone acetonide for ischaemic macular oedema caused by
      branch retinal vein occlusion.

PMID- 14693797
TI  - 360 degree giant retinal tear as a result of presumed non-accidental injury.

PMID- 14693798
TI  - CNV subtype in first eyes predicts severity of ARM in fellow eyes.

PMID- 14693799
TI  - Time to learn from what is known.

PMID- 14693800
TI  - A new look at ophthalmodynamometry.

PMID- 14693802
TI  - Twelve C2H2 zinc-finger genes on human chromosome 19 can be each translated into
      the same type of protein after frameshifts.
AB  - We report a discovery that, of the 226 C2H2 zinc-finger (C2H2-ZNF) genes on human
      chromosome 19, 12 genes each have two open reading frames (ORFs) that are in
      different reading frames but that can be translated into the same type of C2H2
      ZNF proteins. We came to this observation after using standard tools in an
      original manner. First, we found that the both ORFs of such a gene contained the
      same type of significant C2H2-ZNF domain with e-values of e-2 or better. Second,
      the both ORFs had a promoter, a transcription start site, a start codon, a Kozak
      pattern and a poly(A) site; hence, each of them can be viewed as a gene in terms
      of a gene's primary structure. Third, both the ORFs matched not only human C2H2
      ZNF expressed sequence tags (ESTs) but also human C2H2-ZNF proteins with e-values
      of e-50 or better. This indicates that the both ORFs can be transcribed and
      translated into the same zinc-finger proteins. More importantly, we observed that
      the phenomenon-a DNA can be translated into the same type of proteins after a
      frameshift-also occurred in a set of 160 human C2H2-ZNF ESTs and in a set of nine
      cDNAs of human C2H2-ZNF proteins. This observation based on the two sets of wet
      experimental data much strengthened our confidence on the discovery. Our
      discovery is useful in the deeper understanding of a gene's regulatory mechanism
      to maintain its function.

PMID- 14693803
TI  - Identifying periodically expressed transcripts in microarray time series data.
AB  - MOTIVATION: Microarray experiments are now routinely used to collect large-scale
      time series data, for example to monitor gene expression during the cell cycle.
      Statistical analysis of this data poses many challenges, one being that it is
      hard to identify correctly the subset of genes with a clear periodic signature.
      This has lead to a controversial argument with regard to the suitability of both
      available methods and current microarray data. METHODS: We introduce two simple
      but efficient statistical methods for signal detection and gene selection in gene
      expression time series data. First, we suggest the average periodogram as an
      exploratory device for graphical assessment of the presence of periodic
      transcripts in the data. Second, we describe an exact statistical test to
      identify periodically expressed genes that allows one to distinguish periodic
      from purely random processes. This identification method is based on the so
      called g-statistic and uses the false discovery rate approach to multiple
      testing. RESULTS: Using simulated data it is shown that the suggested method is
      capable of identifying cell-cycle-activated genes in a gene expression data set
      even if the number of the cyclic genes is very small and regardless the presence
      of a dominant non-periodic component in the data. Subsequently, we re-examine 12
      large microarray time series data sets (in part controversially discussed) from
      yeast, human fibroblast, human HeLa and bacterial cells. Based on the statistical
      analysis it is found that a majority of these data sets contained little or no
      statistical significant evidence for genes with periodic variation linked to cell
      cycle regulation. On the other hand, for the remaining data the method extends
      the catalog of previously known cell-cycle-specific transcripts by identifying
      additional periodic genes not found by other methods. The problem of
      distinguishing periodicity due to generic cell cycle activity and to artifacts
      from synchronization is also discussed. AVAILABILITY: The approach has been
      implemented in the R package GeneTS available from http://www.stat.uni
      muenchen.de/~strimmer/software.html under the terms of the GNU General Public
      License.

PMID- 14693804
TI  - Prediction of protein subcellular locations using fuzzy k-NN method.
AB  - MOTIVATION: Protein localization data are a valuable information resource helpful
      in elucidating protein functions. It is highly desirable to predict a protein's
      subcellular locations automatically from its sequence. RESULTS: In this paper,
      fuzzy k-nearest neighbors (k-NN) algorithm has been introduced to predict
      proteins' subcellular locations from their dipeptide composition. The prediction
      is performed with a new data set derived from version 41.0 SWISS-PROT databank,
      the overall predictive accuracy about 80% has been achieved in a jackknife test.
      The result demonstrates the applicability of this relative simple method and
      possible improvement of prediction accuracy for the protein subcellular
      locations. We also applied this method to annotate six entirely sequenced
      proteomes, namely Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila
      melanogaster, Oryza sativa, Arabidopsis thaliana and a subset of all human
      proteins. AVAILABILITY: Supplementary information and subcellular location
      annotations for eukaryotes are available at
      http://166.111.30.65/hying/fuzzy_loc.htm

PMID- 14693805
TI  - Efficient filtering methods for clustering cDNAs with spliced sequence alignment.
AB  - MOTIVATION: Clustering sequences of a full-length cDNA library into alternative
      splice form candidates is a very important problem. RESULTS: We developed a new
      efficient algorithm to cluster sequences of a full-length cDNA library into
      alternative splice form candidates. Current clustering algorithms for cDNAs tend
      to produce too many clusters containing incorrect splice form candidates. Our
      algorithm is based on a spliced sequence alignment algorithm that considers
      splice sites. The spliced sequence alignment algorithm is a variant of an
      ordinary dynamic programming algorithm, which requires O(nm) time for checking a
      pair of sequences where n and m are the lengths of the two sequences. Since the
      time bound is too large to perform all-pair comparison for a large set of
      sequences, we developed new techniques to reduce the computation time without
      affecting the accuracy of the output clusters. Our algorithm was applied to 21
      076 mouse cDNA sequences of the FANTOM 1.10 database to examine its performance
      and accuracy. In these experiments, we achieved about 2-12-fold speedup against a
      method using only a traditional hash-based technique. Moreover, without using any
      information of the mouse genome sequence data or any gene data in public
      databases, we succeeded in listing 87-89% of all the clusters that biologists
      have annotated manually. AVAILABILITY: We provide a web service for cDNA
      clustering located at https://access.obigrid.org/ibm/cluspa/, for which
      registration for the OBIGrid (http://www.obigrid.org) is required.

PMID- 14693806
TI  - Protein beta-turn prediction using nearest-neighbor method.
AB  - MOTIVATION: With the emerging success of protein secondary structure prediction
      through the applications of various statistical and machine learning techniques,
      similar techniques have been applied to protein beta-turn prediction. In this
      study, we perform protein beta-turn prediction using a k-nearest neighbor method,
      which is combined with a filter that uses predicted protein secondary structure
      information. Traditional beta-turn prediction from k-nearest neighbor method is
      modified to account for the unbalanced ratio of the natural occurrence of beta
      turns and non-beta-turns. RESULTS: Our prediction scheme is tested on a set of
      426 non-homologous protein sequences. The prediction scheme consists of two
      stages: k-nearest neighbor method stage and filtering stage. Variations of the k
      nearest neighbor method were used to take property of beta-turns into
      consideration. Our filtering method uses beta-turn/non-beta-turn estimates from
      the k-nearest neighbor method stage and predicted protein secondary structure
      information from PSI-PRED in order to get new beta-turn/non-beta-turn estimate.
      Our result is compared with the previously best known beta-turn prediction method
      on the dataset of 426 non-homologous protein sequences and is shown to give
      slightly superior performance at significantly lower computational complexity.
      AVAILABILITY: Contact the author for information on the source code of the
      programs used.

PMID- 14693807
TI  - ClusPro: an automated docking and discrimination method for the prediction of
      protein complexes.
AB  - MOTIVATION: Predicting protein interactions is one of the most challenging
      problems in functional genomics. Given two proteins known to interact, current
      docking methods evaluate billions of docked conformations by simple scoring
      functions, and in addition to near-native structures yield many false positives,
      i.e. structures with good surface complementarity but far from the native.
      RESULTS: We have developed a fast algorithm for filtering docked conformations
      with good surface complementarity, and ranking them based on their clustering
      properties. The free energy filters select complexes with lowest desolvation and
      electrostatic energies. Clustering is then used to smooth the local minima and to
      select the ones with the broadest energy wells-a property associated with the
      free energy at the binding site. The robustness of the method was tested on sets
      of 2000 docked conformations generated for 48 pairs of interacting proteins. In
      31 of these cases, the top 10 predictions include at least one near-native
      complex, with an average RMSD of 5 A from the native structure. The docking and
      discrimination method also provides good results for a number of complexes that
      were used as targets in the Critical Assessment of PRedictions of Interactions
      experiment. AVAILABILITY: The fully automated docking and discrimination server
      ClusPro can be found at http://structure.bu.edu

PMID- 14693808
TI  - Light-weight integration of molecular biological databases.
AB  - MOTIVATION: Due to the increasing number of molecular biological databases and
      the exponential growth of their contents, database integration is an important
      topic of research in bioinformatics. Existing approaches in this area have in
      common that considerable efforts are needed to provide integrated access to
      heterogeneous data sources. RESULTS: This article describes the LIMBO
      architecture as a light-weight approach to molecular biological database
      integration. By building systems upon this architecture, the efforts needed for
      database integration can be significantly lowered. AVAILABILITY: As an
      illustration of the principle usefulness of the underlying ideas, a prototypical
      implementation based upon the LIMBO architecture is described. This
      implementation is exclusively based on freely available open source components
      like the PostgreSQL database management system and the BioRuby project.
      Additional files and modified components are available upon request from the
      author.

PMID- 14693809
TI  - An iterated loop matching approach to the prediction of RNA secondary structures
      with pseudoknots.
AB  - MOTIVATION: Pseudoknots have generally been excluded from the prediction of RNA
      secondary structures due to its difficulty in modeling. Although, several dynamic
      programming algorithms exist for the prediction of pseudoknots using
      thermodynamic approaches, they are neither reliable nor efficient. On the other
      hand, comparative methods are more reliable, but are often done in an ad hoc
      manner and require expert intervention. Maximum weighted matching, an algorithm
      for pseudoknot prediction with comparative analysis, suffers from low-prediction
      accuracy in many cases. RESULTS: Here we present an algorithm, iterated loop
      matching, for reliably and efficiently predicting RNA secondary structures
      including pseudoknots. The method can utilize either thermodynamic or comparative
      information or both, thus is able to predict pseudoknots for both aligned and
      individual sequences. We have tested the algorithm on a number of RNA families.
      Using 8-12 homologous sequences, the algorithm correctly identifies more than 90%
      of base-pairs for short sequences and 80% overall. It correctly predicts nearly
      all pseudoknots and produces very few spurious base-pairs for sequences without
      pseudoknots. Comparisons show that our algorithm is both more sensitive and more
      specific than the maximum weighted matching method. In addition, our algorithm
      has high-prediction accuracy on individual sequences, comparable with the PKNOTS
      algorithm, while using much less computational resources. AVAILABILITY: The
      program has been implemented in ANSI C and is freely available for academic use
      at http://www.cse.wustl.edu/~zhang/projects/rna/ilm/ SUPPLEMENTARY INFORMATION:
      http://www.cse.wustl.edu/~zhang/projects/rna/ilm/

PMID- 14693810
TI  - Distribution of words with a predefined range of mismatches to a DNA probe in
      bacterial genomes.
AB  - MOTIVATION: Hybridization of oligonucleotides with longer nucleotide sequences is
      an essential step in nucleic acid biosynthesis in vitro and in vivo, in
      oligonucleotide-based diagnostics, and in therapeutic applications of
      oligonucleotides. A major factor determining sensitivity and selectivity of
      hybridization is the number of base pair mismatches that occur in an ungapped
      alignment of the oligonucleotide (probe) and a longer sequence (target). RESULTS:
      The k-distance match count between the probe and the target is defined as the
      number of ungapped alignments between the two sequences that have exactly k
      mismatches, and the k-neighbor match count is defined as the sum of the j
      distance match counts for j between 0 and k. We derive a novel formula for the
      probability of a k-distance match. This formula is based on the assumption that
      the target is strand-symmetric Bernoulli text (i.e. nucleotides are
      independently, identically distributed in the target and satisfy Chargaff's
      second parity rule). Our model predicts that the GC-content in both the probe and
      the target significantly affects the match count expectation. The ratio of k
      neighbor match counts in two distinct genomes for a given probe is a measure of
      its specificity. We calculated such ratios for pairs of bacterial genomes with
      different combinations of length, GC-content and phylogenetic distance.
      Examination of the extreme values of these ratios indicates that probes with a
      high discriminative power exist for each tested pair.

PMID- 14693811
TI  - MedBlast: searching articles related to a biological sequence.
AB  - In the genomic era, researchers often want to know more information about a
      biological sequence by retrieving its related articles. However, there is no
      available tool yet to achieve conveniently this goal. Here we developed a new
      literature-mining tool MedBlast, which uses natural language processing
      techniques, to retrieve the related articles of a given sequence. An online
      server of this program is also provided. AVAILABILITY: Both online server and the
      program are available freely at http://medblast.sibsnet.org

PMID- 14693812
TI  - Adaptive stochastic-deterministic chemical kinetic simulations.
AB  - MOTIVATION: Biochemical signaling pathways and genetic circuits often involve
      very small numbers of key signaling molecules. Computationally expensive
      stochastic methods are necessary to simulate such chemical situations. Single
      molecule chemical events often co-exist with much larger numbers of signaling
      molecules where mass-action kinetics is a reasonable approximation. Here, we
      describe an adaptive stochastic method that dynamically chooses between
      deterministic and stochastic calculations depending on molecular count and
      propensity of forward reactions. The method is fixed timestep and has first order
      accuracy. We compare the efficiency of this method with exact stochastic methods.
      RESULTS: We have implemented an adaptive stochastic-deterministic approximate
      simulation method for chemical kinetics. With an error margin of 5%, the method
      solves typical biologically constrained reaction schemes more rapidly than exact
      stochastic methods for reaction volumes >1-10 micro m(3). We have developed a
      test suite of reaction cases to test the accuracy of mixed simulation methods.
      AVAILABILITY: Simulation software used in the paper is freely available from
      http://www.ncbs.res.in/kinetikit/download.html

PMID- 14693813
TI  - VizStruct: exploratory visualization for gene expression profiling.
AB  - MOTIVATION: DNA arrays provide a broad snapshot of the state of the cell by
      measuring the expression levels of thousands of genes simultaneously.
      Visualization techniques can enable the exploration and detection of patterns and
      relationships in a complex data set by presenting the data in a graphical format
      in which the key characteristics become more apparent. The dimensionality and
      size of array data sets however present significant challenges to visualization.
      The purpose of this study is to present an interactive approach for visualizing
      variations in gene expression profiles and to assess its usefulness for
      classifying samples. RESULTS: The first Fourier harmonic projection was used to
      map multi-dimensional gene expression data to two dimensions in an implementation
      called VizStruct. The visualization method was tested using the differentially
      expressed genes identified in eight separate gene expression data sets. The
      samples were classified using the oblique decision tree (OC1) algorithm to
      provide a procedure for visualization-driven classification. The classifiers were
      evaluated by the holdout and the cross-validation techniques. The proposed method
      was found to achieve high accuracy. AVAILABILITY: Detailed mathematical
      derivation of all mapping properties as well as figures in color can be found as
      supplementary on the web page
      http://www.cse.buffalo.edu/DBGROUP/bioinformatics/supplementary/vizstruct. All
      programs were written in Java and Matlab and software code is available by
      request from the first author.

PMID- 14693814
TI  - A global test for groups of genes: testing association with a clinical outcome.
AB  - MOTIVATION: This paper presents a global test to be used for the analysis of
      microarray data. Using this test it can be determined whether the global
      expression pattern of a group of genes is significantly related to some clinical
      outcome of interest. Groups of genes may be any size from a single gene to all
      genes on the chip (e.g. known pathways, specific areas of the genome or clusters
      from a cluster analysis). RESULT: The test allows groups of genes of different
      size to be compared, because the test gives one p-value for the group, not a p
      value for each gene. Researchers can use the test to investigate hypotheses based
      on theory or past research or to mine gene ontology databases for interesting
      pathways. Multiple testing problems do not occur unless many groups are tested.
      Special attention is given to visualizations of the test result, focussing on the
      associations between samples and showing the impact of individual genes on the
      test result. AVAILABILITY: An R-package globaltest is available from
      http://www.bioconductor.org

PMID- 14693815
TI  - A generalized likelihood ratio test to identify differentially expressed genes
      from microarray data.
AB  - MOTIVATION: Microarray technology emerges as a powerful tool in life science. One
      major application of microarray technology is to identify differentially
      expressed genes under various conditions. Currently, the statistical methods to
      analyze microarray data are generally unsatisfactory, mainly due to the lack of
      understanding of the distribution and error structure of microarray data.
      RESULTS: We develop a generalized likelihood ratio (GLR) test based on the two
      component model proposed by Rocke and Durbin to identify differentially expressed
      genes from microarray data. Simulation studies show that the GLR test is more
      powerful than commonly used methods, like the fold-change method and the two
      sample t-test. When applied to microarray data, the GLR test identifies more
      differentially expressed genes than the t-test, has a lower false discovery rate
      and shows more consistency over independently repeated experiments. AVAILABILITY:
      The approach is implemented in software called GLR, which is freely available for
      downloading at http://www.cc.utah.edu/~jw27c60

PMID- 14693816
TI  - Adjustment of systematic microarray data biases.
AB  - MOTIVATION: Systematic differences due to experimental features of microarray
      experiments are present in most large microarray data sets. Many different
      experimental features can cause biases including different sources of RNA,
      different production lots of microarrays or different microarray platforms. These
      systematic effects present a substantial hurdle to the analysis of microarray
      data. RESULTS: We present here a new method for the identification and adjustment
      of systematic biases that are present within microarray data sets. Our approach
      is based on modern statistical discrimination methods and is shown to be very
      effective in removing systematic biases present in a previously published breast
      tumor cDNA microarray data set. The new method of 'Distance Weighted
      Discrimination (DWD)' is shown to be better than Support Vector Machines and
      Singular Value Decomposition for the adjustment of systematic microarray effects.
      In addition, it is shown to be of general use as a tool for the discrimination of
      systematic problems present in microarray data sets, including the merging of two
      breast tumor data sets completed on different microarray platforms. AVAILABILITY:
      Matlab software to perform DWD can be retrieved from
      https://genome.unc.edu/pubsup/dwd/

PMID- 14693817
TI  - Essentiality and damage in metabolic networks.
AB  - Understanding the architecture of physiological functions from annotated genome
      sequences is a major task for postgenomic biology. From the annotated genome
      sequence of the microbe Escherichia coli, we propose a general quantitative
      definition of enzyme importance in a metabolic network. Using a graph analysis of
      its metabolism, we relate the extent of the topological damage generated in the
      metabolic network by the deletion of an enzyme to the experimentally determined
      viability of the organism in the absence of that enzyme. We show that the network
      is robust and that the extent of the damage relates to enzyme importance. We
      predict that a large fraction (91%) of enzymes causes little damage when removed,
      while a small group (9%) can cause serious damage. Experimental results confirm
      that this group contains the majority of essential enzymes. The results may
      reveal a universal property of metabolic networks.

PMID- 14693818
TI  - GIS: a biomedical text-mining system for gene information discovery.
AB  - We present a biomedical text-mining system focused on four types of gene-related
      information: biological functions, associated diseases, related genes and gene
      gene relations. The aim of this system is to provide researchers an easy-to-use
      bio-information service that will rapidly survey the rapidly burgeoning
      biomedical literature. AVAILABILITY: http://iir.csie.ncku.edu.tw/~yuhc/gis/

PMID- 14693819
TI  - GRIL: genome rearrangement and inversion locator.
AB  - GRIL is a tool to automatically identify collinear regions in a set of bacterial
      size genome sequences. GRIL uses three basic steps. First, regions of high
      sequence identity are located. Second, some of these regions are filtered based
      on user-specified criteria. Finally, the remaining regions of sequence identity
      are used to define significant collinear regions among the sequences. By locating
      collinear regions of sequence, GRIL provides a basis for multiple genome
      alignment using current alignment systems. GRIL also provides a basis for using
      current inversion distance tools to infer phylogeny. AVAILABILITY: GRIL is
      implemented in C++ and runs on any x86-based Linux or Windows platform. It is
      available from http://asap.ahabs.wisc.edu/gril

PMID- 14693820
TI  - HOMGL-comparing genelists across species and with different accession numbers.
AB  - Homology Gene List (HOMGL) is a web-based tool for comparing gene lists with
      different accession numbers and identifiers and between different organisms.
      UniGene, LocusLink, HomoloGene and Ensembl databases are utilized to map between
      these lists and to retrieve upstream or transcribed sequences for genes in these
      lists. We illustrate the use of HOMGL with respect to microarray studies and
      promoter analysis. AVAILABILITY: http://homgl.biologie.hu-berlin.de/

PMID- 14693821
TI  - WILMA-automated annotation of protein sequences.
AB  - Large-scale annotation of sets of proteins is a frequently occurring task in
      association with genome sequencing projects. Here, we present an automated
      platform for the functional annotation of large sets of protein sequences.
      Various bioinformatics tools are used to achieve a comprehensive description of
      protein sequences and to link these results to standard Gene Ontology descriptors
      for molecular function, biological processes and cellular components. Access to
      the annotation is provided via a web-interface and database queries. These
      interfaces allow to formulate proteome wide queries as well as the investigation
      of details of individual results. WILMA annotations of the proteomes of Homo
      sapiens, Mus musculus, Arabidopsis thaliana and Caenorhabditis elegans are
      accessible at http://www.came.sbg.ac.at/wilma/

PMID- 14693822
TI  - BugView: a browser for comparing genomes.
AB  - BugView is a Java application for visualizing homologous genes on a pair of
      related genomes, and can also be used to view individual genomes. It accepts
      files of prokaryotic or eukaryotic genomes in GenBank format and allows users to
      assign homologous pairs, and make and save annotations. AVAILABILITY:
      http://www.gla.ac.uk/~dpl1n/BugView/

PMID- 14693823
TI  - The genomic threading database.
AB  - The Genomic Threading Database currently contains structural annotations for the
      genomes of over 100 recently sequenced organisms. Annotations are carried out by
      using our modified GenTHREADER software and through implementing grid technology.
      AVAILABILITY: http://bioinf.cs.ucl.ac.uk/GTD

PMID- 14693824
TI  - PARIS: a proteomic analysis and resources indexation system.
AB  - We developed a system for managing data from two-dimensional electrophoresis
      based proteomic experiments. Named PARIS, the system stores gel image and
      information about experiments and analysis procedures, allows the user to search
      and navigate in genomic and proteomic data, supports visual verification and
      validation of the analysis results, and provides tools for cross multi-experiment
      and multi-experimenter data validation and exploration. AVAILABILITY: The
      software is freely available from
      http://www.inra.fr/bia/J/imaste/Projets/PARIS/index.html

PMID- 14693825
TI  - TM or not TM: transmembrane protein prediction with low false positive rate using
      DAS-TMfilter.
AB  - Web-based servers implementing the DAS-TMfilter algorithm have been launched at
      three mirror sites and their usage is described. The underlying computer program
      is an upgraded and modified version of the DAS-prediction method. The new server
      is (approximately 1 among 100 unrelated queries) while the high efficiency of the
      original algorithm locating TM segments in queries is preserved (sensitivity of
      approximately 95% among documented proteins with helical TM regions).
      AVAILABILITY: The server operates at three mirror sites:
      http://mendel.imp.univie.ac.at/sat/DAS/DAS.html,
      http://wooster.bip.bham.ac.uk/DAS.html and http://www.enzim.hu/DAS/DAS.html. The
      program is available on request.

PMID- 14693826
TI  - Best Practice No 175. Guidelines for virological and non-viral serological
      examination of specimens in routine diagnostic microbiological laboratories.
AB  - Viral examination is routinely carried out in most routine diagnostic
      microbiology laboratories. Most often, this comprises the detection of viral
      antigens and antibodies, and less commonly the isolation of viruses and the
      detection of viral nucleic acids. However, there are no standards or guidelines
      available for processing these specimens in routine diagnostic laboratories or
      for referral to specialist virology centres or units. Clinical Pathology
      Accreditation (CPA) has defined standards for assessing the quality of service
      provided by laboratories, but these do not include the scientific and technical
      aspects of provision of service. The Association of Medical Microbiologists has
      recently published Standards for Laboratory practice in medical microbiology,
      which covers scientific and technical aspects of provision of microbiology
      service, mainly bacteriological examination of specimens in routine diagnostic
      microbiology laboratories. These guidelines are complementary to the CPA
      guidelines and aim to ensure a consistent and high quality service. This article
      presents guidelines for the examination of specimens for the diagnosis of viral
      infections.

PMID- 14693829
TI  - Minimal metastatic disease.

PMID- 14693828
TI  - Micrometastases in neuroblastoma: are they clinically important?
AB  - Despite advances in the treatment of neuroblastoma (NBL), recurrence and
      metastases continue to pose major problems in clinical management. The relation
      between micrometastases and the development of secondary disease is not fully
      understood. However, accurate methods to detect low numbers of tumour cells may
      allow the evaluation of their role in the disease process, and by implication the
      possible benefits of eliminating them. Although there is substantial evidence for
      the increased sensitivity of current molecular methods for the detection of NBL
      cells compared with more conventional cytology, the clinical relevance and
      usefulness of detecting this disease remain controversial. The primary goal of
      current translational research must be to evaluate the clinical relevance of
      micrometastatic disease detected by these methods in multicentre prospective
      clinical outcome studies. Only then can the clinical usefulness of these methods
      be defined so that they may be introduced into relevant clinical practice.

PMID- 14693827
TI  - The eicosanoid cascade: possible role in gliomas and meningiomas.
AB  - Eicosanoids constitute a large family of biologically active lipid mediators that
      are produced by two enzyme classes, cyclooxygenases (COX-1 and COX-2) and
      lipoxygenases (5-LO, 12-LO, and 15-LO). Increasing evidence suggests that in
      addition to a variety of epithelial malignancies, the two most common types of
      human brain tumour, gliomas and meningiomas, aberrantly overexpress eicosanoid
      producing enzymes and release a spectrum of eicosanoids that may promote
      tumorigenesis and the development of peritumorous brain oedema. Glioma and
      meningioma cells are killed in vitro and in animal models when exposed to COX-2
      and 5-LO inhibitors, and their effectiveness is under investigation in clinical
      trials for treatment of patients with malignant brain tumours. However, despite
      research into the role of the eicosanoid cascade in the tumorigenesis of human
      brain tumours, many important questions remain unanswered. Current and newer
      agents that specifically target key players of the eicosanoid cascade could
      change the approach to treating brain tumours, because their benefits may lie in
      their synergism with conventional cytotoxic treatments and/or with other novel
      agents targeted against other procarcinogenic pathways.

PMID- 14693830
TI  - Effects of clinical service reorganisation on cellular pathology workload.
AB  - AIMS: To assess changes in volume and complexity of cellular pathology workload
      after clinical service reorganisation and alterations in pathology reporting
      practices, and to identify objective measures of change applicable to all
      cellular pathology departments. The ear, nose, and throat (ENT), head and neck
      (HN) specialty was chosen for assessment. METHODS: Cellular pathology workload
      from the ENT-HN surgical specialty was assessed numerically and the complexity in
      examination of cancer resection specimens was evaluated. Medical and technical
      time inputs in the reporting of ENT-HN cancer resections were measured
      prospectively, and the histological and cytological workload arising from the
      management of such cases was obtained. RESULTS: The 88.83% increase in ENT-HN
      specimens contrasted with a 13.53% increase in total surgical workload.
      Substantial increases in work complexity were found when measured as
      blocks/slides for each case and number of histochemical/immunohistochemical
      requests. On average, examination of one ENT-HN cancer case consumed 55% of one
      pathologist's work session and over one 10th of a technician's working week. On
      average, each cancer generated 3.3 histological and 1.06 cytological specimens.
      CONCLUSIONS: Evidence is provided of the increase in cellular pathology workload
      and in its complexity. This study lists objective measures of complexity
      applicable to all pathology subspecialties. Given the workforce crisis and
      expanding clinical needs, realistic workload calculations should include
      measurement of complexity and not just volumes.

PMID- 14693831
TI  - The impact of involvement of biomedical scientists in specimen dissection and
      selection of blocks for histopathology: a study of time benefits and specimen
      handling quality in Ayrshire and Arran area laboratory.
AB  - AIMS: To assess possible time benefits of specimen dissection by biomedical
      scientists (BMSs) and the quality of specimen handling by BMSs, in a department
      where BMSs trim those specimens requiring simple descriptions, from which
      standard blocks are taken. METHODS: Specimen handling by BMSs and consultant
      pathologists was compared. Time taken for each specimen trimmed was recorded
      prospectively. To determine specimen handling quality, adherence to dissection
      standard operating procedures (SOPs) was assessed by recording retrospectively
      whether or not each action in the SOP had been performed. Information on
      subsequently required extra levels or blocks was recorded. RESULTS: Analysis of
      data from 672 specimens trimmed by consultants showed that any given action in
      the SOPs was performed on average on 60.2% of applicable/assessable specimens;
      for 660 similar specimens trimmed by BMSs, each action was performed on average
      on 80.1% of specimens. Of the specimens where data on extra blocks were recorded,
      extra blocks were required in 3% of those trimmed by pathologists and in 4% of
      those trimmed by BMSs. Extra levels were required in 12% of those trimmed by
      pathologists and in 16% of those trimmed by BMSs. BMS trimming saves 16 hours of
      consultant time each month. The difference between pathologists and BMSs in time
      for each specimen trimmed is negligible. CONCLUSIONS: The advantages of increased
      adherence to trimming SOPs and saving consultant time outweigh the relatively
      small number of extra blocks and levels required when BMSs trim. There is no
      reduction in quality of dissection.

PMID- 14693832
TI  - Decreased mineralocorticoid receptor expression in blood cells of kidney
      transplant recipients undergoing immunosuppressive treatment: cost efficient
      determination by quantitative PCR.
AB  - AIMS: Electrolyte imbalances caused by impaired ion transport are a frequent side
      effect of immunosuppressive treatment in renal transplant recipients. Clinical
      symptoms resemble features of hypoaldosteronism, although concentrations of
      aldosterone are in the normal range. Because immunosuppression might affect the
      hormone receptor status of cells, mineralocorticoid receptor (hMR) expression by
      peripheral blood leucocytes (PBL) was studied in these patients. METHODS: Twenty
      one renal transplant recipients being treated with cyclosporine A and 19 healthy
      controls were tested. hMR expression was quantified by means of competitive
      reverse transcription polymerase chain reaction (cRT-PCR) and compared with
      receptor binding studies with subsequent Scatchard plot analysis carried out
      previously on 20 renal transplant recipients and 25 controls. Advantages of PCR
      were summarised and compared with Scatchard plot analysis. RESULTS: Cyclosporine
      A caused a 37% decrease in hMR molecules on PBL in 75% of renal transplant
      recipients, and this effect was attributable to the downregulation of hMR
      transcription. PCR was 99% specific for the detection of hMR in PBL and highly
      reproducible. CONCLUSIONS: Decreases in hMR protein and RNA in PBL of transplant
      recipients revealed an inhibitory effect of cyclosporine A on hMR transcription.
      Because hMR acts as a transcription factor, the expression of several genes
      involved in electrolyte homeostasis is affected, leading to signs of
      nephrotoxicity that require therapeutic adjustments. Because of the small volume
      of blood, the assay can be repeated during treatment and is therefore useful for
      measuring treatment outcomes. Lower costs and the absence of radioactive
      challenge are further advantages of the PCR method.

PMID- 14693833
TI  - Prevalence of gastric precancerous lesions in Ardabil, a high incidence province
      for gastric adenocarcinoma in the northwest of Iran.
AB  - BACKGROUND/AIMS: Ardabil Province, in northwestern Iran, has the highest rate of
      gastric (predominantly cardia) adenocarcinoma in Iran. This study aimed to
      investigate the feasibility of endoscopic screening and to look for associated
      Helicobacter pylori infection and gastric precancerous lesions. METHODS: One
      thousand one hundred and five adult volunteers, residents of Ardabil and
      Meshkinshahr, districts, 40 years old and above were selected and invited by a
      simple random household canvass in rural and urban locations. Informed consents
      were obtained and upper gastrointestinal video endoscopy was performed to biopsy
      all visible lesions and standard sites in the antrum, corpus, and cardia.
      RESULTS: One thousand and eleven of the invited individuals agreed to
      participate, including 494 men and 517 women, with a mean (SD) age of 53.32
      (10.39) years. Endoscopy was well tolerated by all subjects; 96.7% of antral and
      80.7% of cardia mucosal biopsies were satisfactory. The urease test or histology
      for H pylori was positive in at least 89.2% of subjects. Histological evidence of
      mucosal atrophy was seen in 39.3% of antral and 21.9% of cardia samples. Chronic
      gastritis with or without activity, reactive atypia of glandular epithelium,
      intestinal metaplasia, dysplasia, and cancer were found in 95.1%, 38.0%, 8.7%,
      0.2%, and 0.3% of antral and 85.3%, 22.9%, 3.8%, 0.3%, and 0.1% of cardiac
      biopsies, respectively. CONCLUSION: Endoscopic screening for upper
      gastrointestinal diseases was feasible and well tolerated in Ardabil, Iran. Most
      subjects showed H pylori infection. Atrophic gastritis, reactive atypia, and
      intestinal metaplasia were common in antrum, corpus, and cardia subsites.

PMID- 14693834
TI  - Lymph node harvests directly influence the staging of colorectal cancer: evidence
      from a regional audit.
AB  - AIMS: To assess the quality of histopathology reporting and accuracy of Dukes's
      staging of colorectal cancers in the former South Western Health region and to
      determine the impact of numbers of lymph nodes examined on stage ascription.
      METHODS: Histopathology reports of colorectal cancer for 1993-7 were analysed.
      Completeness was assessed regarding reported numbers of lymph nodes examined,
      numbers found positive, Dukes's stage, and ICD9 code. Numbers of lymph nodes
      examined, numbers found positive, and Dukes's stage were recorded. Results from
      one hospital known to have high standards of reporting were compared with those
      from elsewhere. RESULTS: In total, 629 reports were examined from the reference
      hospital and 918 from elsewhere. Fewer than one in 20 (4.3%) reports from the
      reference hospital were incomplete, compared with a third (36.1%) elsewhere. The
      average number of nodes examined for each case at the reference hospital was
      18.81 and 6.41 elsewhere. The average number of positive nodes for each case was
      2.47 at the reference hospital and 1.15 elsewhere. The proportion of Dukes's
      stage C cases was significantly higher at the reference hospital than elsewhere.
      Ascertainment of Dukes's stage C cases was related to number of lymph nodes
      examined, with optimal ascertainment levels when at least 10 and fewer than 15
      nodes were examined. CONCLUSIONS: Standards of histopathology reporting, and
      ascertainment of Dukes's stage C, were significantly higher at the reference
      hospital. Variations in ascertainment levels of Dukes's stage C disease mainly
      resulted from variations in the numbers of lymph nodes examined.

PMID- 14693835
TI  - Hep Par 1 expression in carcinoma of the cervix: implications for diagnosis and
      prognosis.
AB  - AIMS: To determine the frequency and pattern of Hep Par 1 expression in cervical
      carcinomas of various histological types and to correlate expression with
      prognostic parameters. METHODS: Twenty nine cervical carcinomas were analysed for
      tumour type, hepatoid and neuroendocrine differentiation, and vascular invasion.
      A semiquantitative analysis was performed for Hep Par 1, alpha fetoprotein,
      chromogranin, and synaptophysin immunoreactivity. RESULTS: Hep Par 1 expression
      was seen in seven of the 29 cervical carcinomas (three of seven adenocarcinomas,
      one of 17 squamous cell carcinomas, one of two adenocarcinomas with
      adenocarcinoma in situ, one of two adenocarcinomas in situ, and one of one large
      cell neuroendocrine carcinoma with adenocarcinoma in situ). Normal looking
      endocervical epithelium was also positive in one case. Cases expressing Hep Par
      1, with or without neuroendocrine coexpression, were associated with a higher
      rate of vascular invasion and a worse prognosis. Three of the five cases
      expressing neuroendocrine markers also coexpressed Hep Par 1. CONCLUSIONS: Hep
      Par 1 expression in carcinoma of the cervix is not uncommon and is present in a
      variety of histological types. Expression of this marker appears to be associated
      with more aggressive biological behaviour and a worse prognosis. The uterine
      cervix is another site that may express Hep Par 1 and hence the use of this
      antibody in situations of diagnostic difficulty, especially involving lesions
      within the liver, have to be coupled with the knowledge of the range of tissues
      it may stain.

PMID- 14693836
TI  - Red cell N5-methyltetrahydrofolate concentrations and C677T
      methylenetetrahydrofolate reductase genotype in patients with stroke.
AB  - AIMS: To investigate the relation between total red cell folate, red cell N(5)
      methyltetrahydrofolate (N(5)MTHF) concentrations, and N(5)N(10)
      methylenetetrahydrofolate reductase (MTHFR) genotypes in stroke. METHODS: The
      study comprised 120 consecutive patients presenting to hospital with acute
      stroke. Multivitamin supplement use was recorded. Serum and red cell folate were
      measured by microbiological assays using Lactobacillus casei and Enterococcus
      faecalis, and by the DPC-BioMediq Immulite 2000 analyser. Total plasma
      homocysteine (tHcy), serum cobalamin, and serum vitamin B(6) were measured and
      the C677T MTHFR genotype determined. RESULTS: There were no significant
      differences in blood tHcy or vitamin concentrations according to MTHFR genotype
      in the overall patient cohort. However, when patients taking vitamins were
      excluded, total red cell folate and red cell N(5)MTHF were significantly lower in
      patients with the TT genotype compared with CT or CC genotypes. In the overall
      cohort, irrespective of genotype, red cell folate was significantly lower when
      assayed microbiologically than with the Immulite assay. This discrepancy remained
      after exclusion of patients taking vitamins. CONCLUSION: Total red cell folate
      and red cell N(5)MTHF are significantly lower in stroke patients with the TT
      compared with the CT and TT MTHFR genotypes, particularly those not taking
      vitamin supplements. Microbiological assays that measure biologically active
      folates provide substantially lower estimates of folate than the Immulite assay.
      Because folate is a key determinant of blood homocysteine values, these findings
      may impact on the interpretation of the strength and independence of the
      association between raised blood concentrations of homocysteine and
      atherothrombosis risk reported in most epidemiological studies.

PMID- 14693837
TI  - Analysis of cell cycle regulator proteins in non-small cell lung cancer.
AB  - BACKGROUND/AIMS: Abnormalities of the proteins involved in cell cycle checkpoints
      are extremely common among almost all neoplasms. This study aimed to investigate
      the expression of four components of the cell cycle machinery-p21, p16, p53, and
      proliferating cell nuclear antigen (PCNA)-in non-small cell lung cancer (NSCLC).
      METHODS: The expression of p21, p16, p53, and PCNA was examined in 68 well
      characterised NSCLC specimens using immunohistochemistry. The coregulation of
      these proteins and their influence on survival were analysed using both
      univariate and multivariate analyses. RESULTS: By univariate analysis, the
      expression of all the proteins examined, except for PCNA, was significantly
      correlated with survival. In multivariate analysis, the only immunohistochemical
      parameter able to influence overall survival was p16, confirming the hypothesis
      that the RB-p16 tumour suppressor pathway is inactivated in most lung cancer
      samples. Finally, the group of patients with NSCLC who were negative for both p21
      and p16 had a significantly shorter overall survival. CONCLUSIONS: These results
      suggest that loss of control of cell cycle checkpoints is a common occurrence in
      lung cancers, and support the idea that functional cooperation between different
      cell cycle inhibitor proteins constitutes another level of regulation in cell
      growth control and tumour suppression.

PMID- 14693839
TI  - Multiple high risk HPV infections are common in cervical neoplasia and young
      women in a cervical screening population.
AB  - AIMS: If human papillomavirus (HPV) testing is to be included within cervical
      screening programmes, the importance of multiple HPV infections in cervical
      neoplasia needs to be determined. This study investigated the diversity of
      multiple HPV types in a routine cervical screening population, and assessed
      associations with cervical neoplasia. METHODS: Overall HPV prevalence, type
      specific prevalence, and extent of multiple infection were assessed in residual
      material from 3444 liquid based cytology samples, using real time GP5+/GP6+
      polymerase chain reaction for screening and linear array assay for genotyping.
      HPV status was studied in relation to age and concurrent cytological evidence of
      dyskaryosis. RESULTS: Twenty per cent of samples were HPV positive. HPV type
      diversity was broad, and multiple HPV infections occurred in half of the HPV
      positive samples. Younger women were significantly more likely to harbour
      multiple high risk HPV (HR-HPV) infections. Infections with multiple HR-HPV types
      were found in 3.4% of samples negative for neoplasia and in 33.3%, 41.8%, and
      40.4% of samples with borderline, mild, or high grade dyskaryosis, respectively.
      Single HR-HPV infections were found in 4.9%, 38.6%, 45.0%, and 51.1% of negative,
      borderline, mild, or high grade dyskaryosis samples, respectively. CONCLUSIONS:
      Multiple HR-HPV infections were most prevalent in young women. Multiple HR-HPV
      infections were not more frequent in high grade than in low grade cervical
      neoplasia, reflecting common sexual transmission of multiple HR-HPV. Prospective
      cohort studies linking sequential loss or gain of HPV types with cytological
      analysis are required to assess the impact of multiple HR-HPV infections on
      neoplastic progression.

PMID- 14693838
TI  - Histopathological patterns of melanoma metastases in sentinel lymph nodes.
AB  - AIMS: Sentinel lymph node biopsy (SLNB) is an important component in the staging
      and treatment of cutaneous melanoma (CM). The medical literature provides only
      limited information regarding melanoma sentinel lymph node (SLN) histology. This
      report details the specific histological patterns of melanoma metastases in
      sentinel lymph nodes (SLNs) and highlights some key factors in evaluating SLNs
      for melanoma. METHODS: From 281 SLNB cases between June 1998 and May 2002, 79
      consecutive cases of SLN biopsies positive for metastases from CM were
      retrospectively reviewed. The important characteristics of the SLNs and the
      metastatic foci are described. RESULTS: The median size of positive SLNs was 17
      mm (range, 5-38). SLNs had a median of two metastatic foci (range, 1-11), with
      the largest foci being a median of 1.1 mm in size (range, 0.05-24). S-100 and HMB
      45 staining was positive in 100% and 92% of the detected metastatic foci,
      respectively. The metastatic melanoma cells were epithelioid, spindled, and mixed
      in 86%, 5%, and 9% of cases. Metastatic foci were most often (86%) found in the
      subcapsular region of the SLN. Benign naevic cells were found coexisting in 14%
      of positive SLNs. CONCLUSIONS: Staining for S100 is more sensitive than HMB-45
      (100% v 92%), but HMB-45 staining helped to distinguish benign naevic cells from
      melanoma. The subcapsular region was crucial in SLN evaluation, because it
      contained the metastases in 86% of cases. Evaluation of the subcapsular space
      should not be compromised by cautery artefacts or incomplete excision of the SLN.

PMID- 14693841
TI  - Expression of DC-SIGN in human foreskin may facilitate sexual transmission of
      HIV.
AB  - This study demonstrates that the human immunodeficiency virus (HIV) binding C
      type lectin DC-SIGN is coexpressed with CD4 and CCR5 on dendritic
      cells/macrophages in human foreskin. It is hypothesised that DC-SIGN may
      contribute to the sexual transmission of HIV in the foreskin, by enabling
      infection of permissive cells in cis and/or in trans.

PMID- 14693840
TI  - Factors affecting metastases to non-sentinel lymph nodes in breast cancer.
AB  - AIMS: Because sentinel lymph node (SLN) biopsy for breast cancer has become well
      established, one of the challenges now is to determine which patients require a
      completion axillary dissection following a positive SLN biopsy. METHODS: A
      prospective database of patients who underwent SLN biopsy for invasive breast
      cancer from July 1999 to November 2002 (n = 180) was analysed. Fifty four
      patients (30%) had one or more positive SLN, and all underwent a completion
      axillary dissection. This subgroup was further analysed to delineate which
      factors predicted non-SLN metastasis. RESULTS: Twenty six of the 54 patients with
      a positive SLN had additional metastases in non-SLNs. Significant variables that
      predicted non-SLN metastasis included extranodal extension (odds ratio (OR),
      17.399; 95% confidence interval (CI), 1.69 to 178.96) and macrometastasis within
      the SLN (OR, 6.985; 95% CI, 1.291 to 37.785). CONCLUSIONS: In patients with
      invasive breast cancer and a positive SLN, extranodal extension or
      macrometastasis within the SLN were both independent predictors of non-SLN
      involvement.

PMID- 14693842
TI  - HCV and HIV binding lectin, DC-SIGNR, is expressed at all stages of HCV induced
      liver disease.
AB  - The process by which hepatitis C virus (HCV) enters cells and the reason for its
      hepatotropism remain obscure. Recently, the human immunodeficiency virus (HIV)
      binding lectins, DC-SIGN and DC-SIGNR, were shown to bind HCV. This article
      reports the expression of DC-SIGN and DC-SIGNR in HCV related liver disease and
      discusses whether these lectins, in particular DC-SIGNR, are responsible for HCV
      hepatotropism.

PMID- 14693843
TI  - Clinical phenotype of haemoglobin Q-H disease.
AB  - Seven patients of Chinese origin who had haemoglobin (Hb) Q-H disease were
      studied. They were found to have a similar clinical phenotype to that of patients
      with deletional Hb H disease, who have a near identical genotypic configuration.
      The complete absence of Hb A in Hb Q-H disease and the similar clinical phenotype
      to deletional Hb H disease lends support to the observation that Hb Q-Thailand
      shares similar functional properties with Hb A.

PMID- 14693844
TI  - Collagenous spherulosis in an adenomyoepithelioma of the breast.
AB  - Collagenous spherulosis (CS) is an incidental finding that usually occurs in
      association with benign proliferative and preinvasive lesions.
      Adenomyoepithelioma is a biphasic neoplasm of the breast, composed of both
      luminal epithelial and myoepithelial cells. Despite the common epimyoepithelial
      histogenesis, CS has never been described in association with
      adenomyoepithelioma. This report describes the case of a 48 year old woman who
      presented with CS of the breast in an adenomyoepithelioma. The combination of
      these two benign lesions led to diagnostic difficulties; namely, differentiation
      from adenoid cystic carcinoma, but also cribriform carcinoma and cylindroma of
      the breast. Antibodies to the oestrogen receptor, progesterone receptor, p63, and
      c-kit (CD117) proved to be useful adjuncts to differentiate between these
      lesions.

PMID- 14693845
TI  - Interdigitating dendritic cell sarcoma of salivary gland associated lymphoid
      tissue not associated with HHV-8 or EBV infection.
AB  - Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare malignancy
      derived from professional antigen presenting cells. This report describes a case
      of IDCS arising in the salivary gland associated lymphoid tissue of the parotid
      gland of a 51 year woman, presenting with a painless neck swelling.
      Histologically, sheets of S100(+)/Ccd68(+)/CD45(+)/CD34(-)/CD1a(-) spindle cells
      were surrounded with an inflammatory infiltrate with no evidence of B or T cell
      clonal proliferations. No evidence of either human herpesvirus 8 or Epstein-Barr
      virus could be detected by quantitative polymerase chain reaction in the tumour
      cells with serological evidence of previous Epstein-Barr virus infection. The
      patient remains well and disease free 24 months after presentation without
      specific treatment.

PMID- 14693846
TI  - Primary sclerosing epithelioid fibrosarcoma of the sacrum: a case report and
      review of the literature.
AB  - Sclerosing epithelioid fibrosarcoma is a rare tumour characterised histologically
      by a predominant population of epithelioid cells arranged in strands and nests,
      embedded in a fibrotic and hyalinised stroma. It is a low grade tumour with an
      indolent course. A 48 year old woman presented with a painful swelling over her
      back for six months. Investigation and biopsy revealed features of sclerosing
      epithelioid fibrosarcoma involving the left half of the sacrum, left sacro-iliac
      joint, and posterior part of the left ilium. Preoperative radiotherapy and wide
      location excision of the tumour were followed by metastatic recurrence of the
      tumour in the lung and scalp six years after initial presentation. The tumour
      showed typical histology of sclerosing epithelioid fibrosarcoma. The radiological
      features confirmed its primary location in the sacrum. The patient declined
      chemotherapy and died of disseminated disease eight years after initial
      presentation. Review of the literature confirms the fact that sclerosing
      epithelioid fibrosarcoma, despite its low grade, is a clinicopathologically
      distinct tumour with full malignant potential, the recurrence, metastasis, and
      mortality rate being 48%, 60%, and 35%, respectively. Sclerosing epithelioid
      fibrosarcoma can occur as a primary bone tumour, the clinical behaviour of which
      is probably similar to its soft tissue counterpart.

PMID- 14693847
TI  - Characterisation of hexon and fibre genes of a novel strain of adenovirus
      involved in epidemic keratoconjunctivitis.
AB  - AIMS: To characterise a novel strain (M86) of adenovirus (Ad) involved in
      epidemic keratoconjunctivitis (EKC). METHODS/RESULTS: The virus strain was
      neutralised by antisera to both Ad35 and Ad11. Restriction endonuclease analysis
      of genomic DNA showed 98% and 88% homology with Ad11 and Ad35, respectively. The
      deduced amino acid sequence of the hypervariable regions of (HVRs) of the hexon
      gene showed a higher homology with Ad35 (94.4%) than with Ad11 (83.7%). However,
      it was 100% homologous to Ad35 in HVRs 1, 2, 3, and 6 and to Ad11 in HVRs 4 and
      6. In the fibre knob, the isolate was more homologous to Ad11 (99.4%) than to
      Ad35 (29.1%). CONCLUSION: This novel strain of adenovirus showed similarities
      with both Ad11 and Ad35. The isolation of a novel strain like Ad35+11 is
      important because of its association with EKC.

PMID- 14693848
TI  - Peroperative frozen section analysis of TTF-1 antigen expression.
AB  - BACKGROUND: The assessment of thyroid transcription factor 1 (TTF-1) expression
      is a useful way to investigate the origin of lung adenocarcinomas or large cell
      carcinomas when dealing with a solitary lung nodule in a patient with a history
      of extrathoracic cancer. However, if immunohistological analysis has not been
      performed before surgery, a peroperative frozen section may be insufficient to
      distinguish between a primary pulmonary tumour and a metastatic tumour. AIMS: To
      develop a technique for the rapid assessment of TTF-1 expression that could
      improve the ability of frozen section peroperative histological diagnosis to
      answer such questions. METHODS: A rapid immunohistochemical technique (lasting 30
      minutes) to assess the expression of TTF-1 was developed and tested. RESULTS:
      Among the 45 interpretable cases, results of frozen section immunohistochemistry
      were similar to those found by the standard immunohistochemical technique for the
      expression of TTF-1. CONCLUSIONS: This technique enables TTF-1 to be analysed
      peroperatively, but further prospective studies are needed to assess its
      usefulness in routine practice.

PMID- 14693849
TI  - Influence of recipient and donor IL-1alpha, IL-4, and TNFalpha genotypes on the
      incidence of acute renal allograft rejection.
AB  - AIMS: To determine whether polymorphisms of the genes encoding donor or recipient
      interleukin 1alpha (IL-1alpha), tumour necrosis factor alpha (TNFalpha), or IL-4
      have any impact on the incidence of acute rejection after renal transplantation.
      METHODS: All donors and recipients were genotyped for three polymorphisms in the
      three cytokine genes: IL1A -889, TNFA -308, and IL4 -590. RESULTS: Statistical
      analysis of the data obtained revealed no association between the cytokine gene
      polymorphisms tested and the incidence of post-transplant acute rejection. After
      stratification for human leucocyte antigen (HLA) matching, it was found that
      kidneys from donors positive for the TNFA-A allele had a significantly increased
      incidence of acute rejection in HLA-DR mismatched transplants. CONCLUSIONS: This
      finding argues for prospective TNFA genotyping of renal donors, with avoidance of
      allocation of kidneys from donors positive for the TNFA-A allele to HLA-DR
      mismatched recipients.

PMID- 14693850
TI  - A comparison of IgG anti-rubella activity in frozen serum stored in primary gel
      separation tubes or secondary tubes.
AB  - AIMS: To determine the suitability of primary gel separation tubes for the
      storage of frozen sera intended for serological testing. METHODS: Blood samples
      from 102 patients were collected into gel separation tubes. The sera from these
      samples were split between the primary gel separation tubes and conventional
      plastic storage tubes and frozen. A year later, the tubes were thawed and anti
      rubella IgG concentrations were compared for the serum pairs using the Wilcoxon
      signed rank test. RESULTS: No significant difference was detected between the two
      storage methods. CONCLUSIONS: Frozen storage of serum samples in primary gel
      separation tubes is a practical alternative to storing separated sera in
      secondary containers. Adopting this practice has advantages for laboratories in
      reducing specimen handling and reducing errors in labelling stored samples.

PMID- 14693851
TI  - Isolated bone marrow mycosis in a patient presenting with consumptive symptoms.

PMID- 14693852
TI  - The role of mast cells in bone marrow diseases.

PMID- 14693853
TI  - The exploding bullet.

PMID- 14693854
TI  - Malignant transformation of a recurrent vestibular schwannoma.

PMID- 14693855
TI  - Best practice guideline on microbiological investigation of infertility requires
      further review.

PMID- 14693856
TI  - Researchers seek resuscitative edge for improving cardiac arrest survival.

PMID- 14693857
TI  - Set a microbe to kill a microbe: drug resistance renews interest in phage
      therapy.

PMID- 14693864
TI  - Ethics consultation in the intensive care unit.

PMID- 14693865
TI  - Ethics consultation in the intensive care unit.

PMID- 14693866
TI  - Identifying patients at risk of recurrent venous thromboembolism.

PMID- 14693867
TI  - Increasing rates of forearm fractures in children.

PMID- 14693868
TI  - Farming and slaughterhouse practices to reduce meat-borne disease.

PMID- 14693869
TI  - Exercise and risk of breast cancer.

PMID- 14693870
TI  - Uses of published physician performance data.

PMID- 14693871
TI  - Effects of reducing the upper limit of normal TSH values.

PMID- 14693872
TI  - Whole-body dual-modality PET/CT and whole-body MRI for tumor staging in oncology.
AB  - CONTEXT: Deciding on the appropriate therapy for patients with malignant diseases
      mandates accurate tumor staging with whole-body coverage. Magnetic resonance
      imaging (MRI) and a combined modality including positron emission tomography
      (PET) and computed tomography (CT) provide whole-body tumor staging in a single
      session. OBJECTIVE: To determine the staging accuracies of both whole-body PET/CT
      and whole-body MRI for different malignant diseases. DESIGN, SETTING, AND
      PATIENTS: Prospective, blinded, investigator-initiated study of 98 patients (mean
      age, 58 years; range, 27-94 years) with various oncological diseases who
      underwent back-to-back whole-body glucose analog [18F]-fluorodeoxyglucose-PET/CT
      and whole-body MRI for tumor staging. The study was conducted at a university
      hospital from December 2001 through October 2002 and had a mean follow-up of 273
      days (range, 75-515 days). The images were evaluated by 2 different, blinded
      reader teams. The diagnostic accuracies of the 2 imaging procedures were
      compared. MAIN OUTCOME MEASURES: Correct classification of the primary tumor,
      regional lymph nodes, and distant metastasis (overall TNM stage) using whole-body
      PET/CT and whole-body MRI. Secondary outcome measures were accurate assessment of
      T-stage, N-stage, and M-stage by the 2 imaging procedures. RESULTS: Of 98
      patients, the overall TNM stage was correctly determined in 75 with PET/CT (77%;
      95% confidence interval [CI], 67%-85%) and in 53 with MRI (54%; 95% CI, 44%-64%)
      (P<.001). Compared with MRI, PET/CT had a direct impact on patient management in
      12 patients. Results from MRI changed the therapy regimen in 2 patients compared
      with PET/CT. Separate assessment of T-stage (with pathological verification) in
      46 patients revealed PET/CT to be accurate in 37 (80%; 95% CI, 66%-91%) and MRI
      to be accurate in 24 (52%; 95% CI, 37%-67%) (P<.001). Of 98 patients, N-stage was
      correctly determined in 91 patients with PET/CT (93%; 95% CI, 86%-97%) and in 77
      patients with MRI (79%; 95% CI, 69%-86%) (P =.001). Both imaging procedures
      showed a similar performance in detecting distant metastases. CONCLUSIONS: The
      feasibility and diagnostic accuracy of the whole-body staging strategies of
      PET/CT and MRI are established. Superior performance in overall TNM staging
      suggests the use of [18F]-fluorodeoxyglucose-PET/CT as a possible first-line
      modality for whole-body tumor staging.

PMID- 14693873
TI  - Impact of valve surgery on 6-month mortality in adults with complicated, left
      sided native valve endocarditis: a propensity analysis.
AB  - CONTEXT: Complicated, left-sided native valve endocarditis causes significant
      morbidity and mortality in adults. The presumed benefits of valve surgery remain
      unproven due to lack of randomized controlled trials. OBJECTIVE: To determine
      whether valve surgery is associated with reduced mortality in adults with
      complicated, left-sided native valve endocarditis. DESIGN AND SETTING:
      Retrospective, observational cohort study conducted from January 1990 to January
      2000 at 7 Connecticut hospitals. Propensity analyses were used to control for
      bias in treatment assignment and prognostic imbalances. PATIENTS: Of the 513
      adults with complicated, left-sided native valve endocarditis, 230 (45%)
      underwent valve surgery and 283 (55%) received medical therapy alone. MAIN
      OUTCOME MEASURE: All-cause mortality at 6 months after baseline. RESULTS: In the
      6-month period after baseline, 131 patients (26%) died. In unadjusted analyses,
      valve surgery was associated with reduced mortality (16% vs 33%; hazard ratio
      [HR], 0.43; 95% confidence interval [CI], 0.29-0.63; P<.001). After adjustment
      for baseline variables associated with mortality (including hospital site,
      comorbidity, congestive heart failure, microbial etiology, immunocompromised
      state, abnormal mental status, and refractory infection), valve surgery remained
      associated with reduced mortality (adjusted HR, 0.35; 95% CI, 0.23-0.54; P<.02).
      In further analyses of 218 patients matched by propensity scores, valve surgery
      remained associated with reduced mortality (15% vs 28%; HR, 0.45; 95% CI, 0.23
      0.86; P =.01). After additional adjustment for variables that contribute to
      heterogeneity and confounding within the propensity-matched group, surgical
      therapy remained significantly associated with a lower mortality (HR, 0.40; 95%
      CI, 0.18-0.91; P =.03). In this propensity-matched group, patients with moderate
      to severe congestive heart failure showed the greatest reduction in mortality
      with valve surgery (14% vs 51%; HR, 0.22; 95% CI, 0.09-0.53; P =.001).
      CONCLUSIONS: Valve surgery for patients with complicated, left-sided native valve
      endocarditis was independently associated with reduced 6-month mortality after
      adjustment for both baseline variables associated with the propensity to undergo
      valve surgery and baseline variables associated with mortality. The reduced
      mortality was particularly evident among patients with moderate to severe
      congestive heart failure.

PMID- 14693874
TI  - Evaluation of control measures implemented in the severe acute respiratory
      syndrome outbreak in Beijing, 2003.
AB  - CONTEXT: Beijing, China, experienced the world's largest outbreak of severe acute
      respiratory syndrome (SARS) beginning in March 2003, with the outbreak resolving
      rapidly, within 6 weeks of its peak in late April. Little is known about the
      control measures implemented during this outbreak. OBJECTIVE: To describe and
      evaluate the measures undertaken to control the SARS outbreak. DESIGN, SETTING,
      AND PARTICIPANTS: Data were reviewed from standardized surveillance forms from
      SARS cases (2521 probable cases) and their close contacts observed in Beijing
      between March 5, 2003, and May 29, 2003. Procedures implemented by health
      authorities were investigated through review of official documents and
      discussions with public health officials. MAIN OUTCOME MEASURES: Timeline of
      major control measures; number of cases and quarantined close contacts and attack
      rates, with changes in infection control measures, management, and triage of
      suspected cases; and time lag between illness onset and hospitalization with
      information dissemination. RESULTS: Health care worker training in use of
      personal protective equipment and management of patients with SARS and
      establishing fever clinics and designated SARS wards in hospitals predated the
      steepest decline in cases. During the outbreak, 30 178 persons were quarantined.
      Among 2195 quarantined close contacts in 5 districts, the attack rate was 6.3%
      (95% confidence interval [CI], 5.3%-7.3%), with a range of 15.4% (95% CI, 11.5%
      19.2%) among spouses to 0.36% (95% CI, 0%-0.77%) among work and school contacts.
      The attack rate among quarantined household members increased with age from 5.0%
      (95% CI, 0%-10.5%) in children younger than 10 years to 27.6% (95% CI, 18.2%
      37.0%) in adults aged 60 to 69 years. Among almost 14 million people screened for
      fever at the airport, train stations, and roadside checkpoints, only 12 were
      found to have probable SARS. The national and municipal governments held 13 press
      conferences about SARS. The time lag between illness onset and hospitalization
      decreased from a median of 5 to 6 days on or before April 20, 2003, the day the
      outbreak was announced to the public, to 2 days after April 20 (P<.001).
      CONCLUSIONS: The rapid resolution of the SARS outbreak was multifactorial,
      involving improvements in management and triage in hospitals and communities of
      patients with suspected SARS and the dissemination of information to health care
      workers and the public.

PMID- 14693875
TI  - Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a
      preliminary study.
AB  - CONTEXT: Severe acute respiratory syndrome (SARS) is a new clinical entity for
      which no effective therapeutic strategy has been developed. OBJECTIVE: To provide
      preliminary results on the potential therapeutic benefit and tolerability of
      interferon alfacon-1 plus corticosteroids for SARS. DESIGN, SETTING, AND
      PATIENTS: Open-label study of 22 patients diagnosed as having probable SARS at
      North York General Hospital, Toronto, Ontario, between April 11 and May 30, 2003.
      INTERVENTIONS: Thirteen patients were treated with corticosteroids alone and 9
      patients were treated with corticosteroids plus subcutaneous interferon alfacon
      1. MAIN OUTCOME MEASURES: Clinical parameters, including oxygen saturation and
      requirement, laboratory measures, and serial chest radiography results. RESULTS:
      Resolution of fever and lymphopenia were similar between the 2 treatment groups.
      Of the 13 patients treated with corticosteroids alone, 5 (38.5%) were transferred
      to the intensive care unit, 3 (23.1%) required intubation and mechanical
      ventilation, and 1 (7.7%) died. Of the 9 patients in the interferon alfacon-1
      treatment group, 3 (33.3%) were transferred to the intensive care unit, 1 (11.1%)
      required intubation and mechanical ventilation, and none died. The interferon
      alfacon-1 treatment group had a shorter time to 50% resolution of lung
      radiographic abnormalities (median time, 4 days vs 9 days; P =.001), had better
      oxygen saturation (P =.02), resolved their need for supplemental oxygen more
      rapidly (median, 10 days vs 16 days; P =.02), had less of an increase in creatine
      kinase levels (P =.03), and showed a trend toward more rapid resolution of
      lactate dehydrogenase levels compared with the group receiving corticosteroids
      alone. CONCLUSIONS: In this preliminary, uncontrolled study of patients with
      SARS, use of interferon alfacon-1 plus corticosteroids was associated with
      reduced disease-associated impaired oxygen saturation, more rapid resolution of
      radiographic lung abnormalities, and lower levels of creatine kinase. These
      findings suggest that further investigation may be warranted to determine the
      role of interferon alfacon-1 as a therapeutic agent for the treatment of SARS.

PMID- 14693876
TI  - Ethical and legal challenges posed by severe acute respiratory syndrome:
      implications for the control of severe infectious disease threats.
AB  - The appearance and spread of severe acute respiratory syndrome (SARS) on a global
      level raised vital legal and ethical issues. National and international responses
      to SARS have profound implications for 3 important ethical values: privacy,
      liberty, and the duty to protect the public's health. This article examines,
      through legal and ethical lenses, various methods that countries used in reaction
      to the SARS outbreak: surveillance and contact tracing, isolation and quarantine,
      and travel restrictions. These responses, at least in some combination, succeeded
      in bringing the outbreak to an end. The article articulates a set of legal and
      ethical recommendations for responding to infectious disease threats, seeking to
      reconcile the tension between the public's health and individual rights to
      privacy, liberty, and freedom of movement. The ethical values that inform the
      recommendations include the precautionary principle, the least
      restrictive/intrusive alternative, justice, and transparency. Development of a
      set of legal and ethical recommendations becomes even more essential when, as was
      true with SARS and will undoubtedly be the case with future epidemics, scientific
      uncertainty is pervasive and urgent public health action is required.

PMID- 14693877
TI  - A 50-year-old man with hepatitis C and cirrhosis needing liver transplantation.

PMID- 14693878
TI  - A 58-year-old man with a diagnosis of chronic Lyme disease, 1 year later.

PMID- 14693879
TI  - Whole-body imaging with MRI or PET/CT: the future for single-modality imaging in
      oncology?

PMID- 14693880
TI  - Evaluating and optimizing outcomes of surgery for endocarditis.

PMID- 14693881
TI  - The SARS response--building and assessing an evidence-based approach to future
      global microbial threats.

PMID- 14693883
TI  - JAMA patient page. Severe acute respiratory syndrome (SARS).

PMID- 14693884
TI  - Is this journal really needed?

PMID- 14693885
TI  - Childhood injuries.

PMID- 14693886
TI  - Speed cameras under attack in the United Kingdom.

PMID- 14693887
TI  - Patricia Fossum Waller, PhD (1932-2003).

PMID- 14693888
TI  - Are mobile speed cameras effective? A controlled before and after study.
AB  - OBJECTIVE: To identify the most appropriate metric to determine the effectiveness
      of mobile speed cameras in reducing road traffic related injuries. DESIGN:
      Controlled before and after study which compares two methods for examining the
      local effectiveness of mobile speed cameras-a circular zone around the camera and
      a route based method to define exposure at various distances from sites. SETTING:
      South Wales, UK. SUBJECTS: Persons injured by road traffic before and after
      intervention. INTERVENTION: Use of mobile speed cameras at 101 sites. MAIN
      OUTCOME MEASURES: Rate ratio of injurious crashes at intervention and control
      sites. RESULTS: Camera sites had lower than expected numbers of injurious crashes
      up to 300 metres using circles and up to 500 metres using routes. Routes methods
      indicated a larger effect than the circles method except in the 100 metres
      nearest sites. A 500 metre route method was used to investigate the effect within
      strata of time after intervention, time of day, speed limit, and type of road
      user injured. The number of injurious crashes after intervention was
      substantially reduced (rate ratio 0.49, 95% confidence interval 0.42 to 0.57) and
      sustained throughout two years after intervention. Significant decreases occurred
      in daytime and night time, on roads with speed limits of 30 and 60-70 miles/hour
      and for crashes that injured pedestrians, motorcycle users, and car occupants.
      CONCLUSIONS: The route based method is the better method of measure effectiveness
      at distances up to 500 metres. This method demonstrates a 51% reduction in
      injurious crashes.

PMID- 14693889
TI  - Unintentional and undetermined firearm related deaths: a preventable death
      analysis for three safety devices.
AB  - OBJECTIVE: To determine the proportion of unintentional and undetermined firearm
      related deaths preventable by three safety devices: personalization devices,
      loaded chamber indicators (LCIs), and magazine safeties. A personalized gun will
      operate only for an authorized user, a LCI indicates when the gun contains
      ammunition, and a magazine safety prevents the gun from firing when the
      ammunition magazine is removed. DESIGN: Information about all unintentional and
      undetermined firearm deaths from 1991-98 was obtained from the Office of the
      Chief Medical Examiner for Maryland, and from the Wisconsin Firearm Injury
      Reporting System for Milwaukee. Data regarding the victim, shooter, weapon, and
      circumstances were abstracted. Coding rules to classify each death as
      preventable, possibly preventable, or not preventable by each of the three safety
      devices were also applied. RESULTS: There were a total of 117 firearm related
      deaths in our sample, 95 (81%) involving handguns. Forty three deaths (37%) were
      classified as preventable by a personalized gun, 23 (20%) by a LCI, and five (4%)
      by a magazine safety. Overall, 52 deaths (44%) were preventable by at least one
      safety device. Deaths involving children 0-17 (relative risk (RR) 3.3, 95%
      confidence interval (CI) 2.1 to 5.1) and handguns (RR 8.1, 95% CI 1.2 to 53.5)
      were more likely to be preventable. Projecting the findings to the entire United
      States, an estimated 442 deaths might have been prevented in 2000 had all guns
      been equipped with these safety devices. CONCLUSION: Incorporating safety devices
      into firearms is an important injury intervention, with the potential to save
      hundreds of lives each year.

PMID- 14693891
TI  - Effect of urban closed circuit television on assault injury and violence
      detection.
AB  - OBJECTIVE: To evaluate the effect of closed circuit television (CCTV)
      surveillance on levels of assault injury and violence detection. DESIGN:
      Intervention versus control study design. SETTING: Five town/cities with CCTV
      surveillance and five, matched control centres without CCTV surveillance in
      England. INTERVENTION: CCTV installation and surveillance. METHODS: Assault
      related emergency department attendances and violent offences recorded by the
      police in CCTV and control centres in the four years, 1995-99, two years before
      and two years after CCTV installation, were compared. RESULTS: Assault related
      emergency department attendances decreased in intervention centres (3% decrease,
      ratio 0.96; 95% confidence interval (CI) 0.93 to 0.99) and increased in control
      centres (11% increase, ratio 1.11; 95% CI 1.08 to 1.14). Overall, changes in
      emergency department assault attendance in CCTV and control centres were
      significantly different (t test, p<0.05). Police recorded violence increased in
      CCTV (11% increase, ratio 1.16; 95% CI 1.08 to 1.24) and control centres (5%
      increase, ratio 1.06; 95% CI 0.99 to 1.13). Overall, changes in police recording
      in CCTV and control centres were not significantly different (t test, p>0.05). In
      CCTV centres, decreases in assault related emergency department attendances and
      increases in police violence detection were not uniform. CONCLUSION: CCTV
      surveillance was associated with increased police detection of violence and
      reductions in injury or severity of injury. CCTV centre variation deserves
      further study.

PMID- 14693892
TI  - Helmet rental practices at United States ski areas: a national survey.
AB  - OBJECTIVES: Studies have shown that head injuries are the leading cause of death
      on ski slopes. Statistics on helmet rental practices at ski areas across the
      United States have never been reported. This study sought to determine the
      prevalence of United States ski areas offering helmet rental during the 2002-03
      ski season. Secondarily it sought to analyze the relationships of geographic
      region and size of ski area with helmet rental availability and to gather
      information on ski helmet rental cost to the consumer. METHODS: and setting: A
      stratified cross sectional telephone survey of a sample of 331 United States ski
      area onsite rental shops during February 2003. RESULTS: Altogether 50% of ski
      areas offered helmet rental with significant variation in the prevalence of
      helmet rental among ski areas of differing regions and sizes (p<0.01). A majority
      of Northeastern (57%), Western (63%), and Rocky Mountain (71%) ski areas rented
      helmets, whereas a minority of Southern (37%) and Midwestern (23%) ski areas
      rented helmets. Twenty five percent of the smallest ski areas (< or =50 acres)
      rented helmets compared with 74% of the largest ski areas (> or =501 acres).
      CONCLUSIONS: United States ski area helmet rental practices vary by region of the
      country and ski area size. Winter sports participants interested in wearing
      protective headgear should be aware of the helmet rental practices at the ski
      area in which they plan to visit and consider helmet purchase if they visit
      mainly smaller ski areas or areas within the South or Midwest.

PMID- 14693893
TI  - Increases in booster seat use among children of low income families and variation
      with age.
AB  - OBJECTIVES: To increase booster seat use among low income parents.
      DESIGN/METHODS: A pre-test/post-test design conducted in nine daycare centers
      with post-test observations four to eight weeks after the intervention.
      INTERVENTION: Parents who participated in an educational training received free
      seats, educational programs were provided to all daycare staff and children, and
      signs in parking lots informed parents about child restraints. At seven centers,
      new policies recommended compliance with state restraint laws. Parents at four
      centers randomly chosen from the seven received financial incentives if observed
      using booster seats. MAIN OUTCOME MEASURE: The percent of children aged 4-8
      riding in booster seats. RESULTS: Pre-test observations of 185 4-8 year olds
      found 56% riding unrestrained and fewer than 3% riding in booster seats. After
      the intervention, observation of 146 children found the number riding in booster
      seats increased to 38% and the number observed without restraints decreased to
      26%. Most booster seat use occurred with 4 and 5 year olds. No 7 or 8 year olds
      rode in booster seats. Changing center policies to recommend compliance with
      state restraint laws and an offer of financial incentives appeared to have no
      additional impact. CONCLUSIONS: Booster seat usage among low income families can
      be increased dramatically, though use decreases with age. Providing free seats
      accompanied by training may be sufficient without the need for additional
      intervention.

PMID- 14693894
TI  - Examining child restraint use and barriers to their use: lessons from a pilot
      study.
AB  - OBJECTIVE: To determine the suitability of four research methods to measure the
      rate of child restraint device (CRD) use and incorrect use in New Zealand and
      obtain data on barriers to CRD use. DESIGN AND SETTING: To assess the rates of
      CRD use among vehicles carrying children 8 years of age and under, two methods
      were piloted-namely, an unobtrusive observational survey and a short interview
      and close inspection. A self administered questionnaire and focus group
      interviews were also piloted to assess CRD use, reasons for use and non-use, and
      to obtain information on barriers to their use. Respondents to all methods except
      the focus groups were approached in supermarket car park sites at randomly
      selected times. Focus groups were established with parents identified through
      early childhood organisations. All methods were assessed on criteria related to
      efficiency, representativeness, and ability to obtain the necessary data.
      RESULTS: The observational survey provided a simple method for identifying rates
      of CRD use, while the self administered questionnaire obtained data on
      demographic characteristics and reported the installation and use/non-use of
      CRDs. The interview/inspection addressed all the questions of both the above
      methods and enabled incorrect CRD use to be examined. The focus groups provided
      the most meaningful information of all methods on barriers to CRD use.
      DISCUSSION: and conclusion: Advantages and limitations of these methods are
      discussed and some refinements of the original instruments are proposed. The
      interview/inspection and focus group methods were identified as being more
      appropriate for efficiently obtaining reliable data on CRD use and identification
      of barriers to CRD use.

PMID- 14693895
TI  - Comparison of urban and rural non-fatal injury: the results of a statewide
      survey.
AB  - OBJECTIVES: This study compared the epidemiology of non-fatal injury among urban
      and rural residents of Colorado. DESIGN: A stratified probability sample with
      random digit dial methods was used to survey Colorado residents by telephone
      regarding injuries experienced in the last 12 months. Questions on the cause of
      the injury, the activity at the time of the injury, and the place of injury were
      based on the Nordic Medico Statistical Committee's (NOMESCO) classification of
      external causes of injuries. SUBJECTS: A total of 1425 urban and 1275 rural
      Colorado residents aged 18 and older were interviewed. RESULTS: Age, gender,
      marital status, and rural residency were found to increase the odds of self
      reported injury. The adjusted odds ratio for self reported injury was 1.3 (95%
      confidence interval (CI) 1.01 to 1.68) for rural compared with urban residents.
      Rural residence (odds ratio 1.02, 95% CI 0.51 to 7.01) was not a risk factor for
      injury among the highest risk group, those who were single and never married. No
      differences in injury characteristics were found by urban-rural status.
      CONCLUSIONS: The increased odds of self reported injury among rural residents
      were not explained by differences in the causes of injury or other injury
      characteristics. The differences in the importance of rural residence in
      increased odds of injury by marital status warrants further understanding and may
      be important in the development of injury prevention programs. Based on
      comparison with a similar survey, the NOMESCO coding system appears to be a
      viable alternative survey tool for gathering information on injury
      characteristics.

PMID- 14693896
TI  - Childhood and adolescence poisoning in NSW, Australia: an analysis of age, sex,
      geographic, and poison types.
AB  - OBJECTIVE: This study aims to investigate whether there is any association
      between the types of poison substances and geographic locations for different age
      groups and sex. DESIGN: This is a population based epidemiological study
      utilising routinely collected inpatient statistics. SETTING: Data are collected
      as part of the routine vital health information system via all hospitals in New
      South Wales (NSW), Australia. PATIENTS: All patients aged between 0-19 years who
      were admitted to a hospital because of poisoning by the four major types of
      substances that were defined in the study in NSW in 2000. MAIN RESULTS: The
      standardised incidence ratios of poisoning related hospitalisation between
      metropolitan and rural areas varied across different poison types when compared
      with the NSW average. While there are few differences between metropolitan and
      rural areas for analgesic and chemical related poisoning admissions across
      different age groups and sex, differences in the standardised incidence ratios
      between geographic locations for psychotropic and venom related poisoning
      admissions were found. No significant difference in standardised mortality ratios
      were found between metropolitan and rural areas except for females in the 10-14
      years age group (standardised mortality ratio 3.24, 95% confidence interval 1.69
      to 6.21). CONCLUSIONS: The results obtained in this study, on the whole, provide
      some evidence for an association between poison types and geographic locations
      for psychotropic and venom related poisoning.

PMID- 14693897
TI  - Being "at fault" in traffic crashes: does alcohol, cannabis, cocaine, or polydrug
      abuse make a difference?
AB  - OBJECTIVE: To compare associations of alcohol, cannabis, and cocaine abuse and
      traffic crash risk for "at fault" crashes and all crashes. DESIGN: A historical
      cohort study. SETTING: Toronto, Ontario. Patients or subjects: Subjects beginning
      treatment at the Centre for Addictions and Mental Health (CAMH) in 1994 for abuse
      of alcohol, cannabis, cocaine, and all combinations of these substances (n = 590,
      with 411 drivers). A control group consisted of 518 records from the Ontario
      registry of registered drivers, frequency matched for age and sex and residence.
      INTERVENTIONS: CAMH subjects took part in therapeutic programs. Pre-intervention
      (11 115 driver-years) and post-intervention intervals (8550 driver-years) were
      defined and compared. MAIN OUTCOME MEASURES: Crash and collision rates, adjusted
      relative risks (ARRs) of crash involvement and of "at fault" crashes were
      computed using Poisson regression to control for variations in time at risk, age,
      and sex of participants. RESULTS: Pre-treatment, significant ARRs of 1.49 to 1.79
      for all crashes were found for abusers of cannabis, cocaine, or a combination.
      ARRs increased by 10%-15% for "at fault" crashes. Post-treatment, all
      associations were very modest for all abuse types. Only younger and male drivers
      had a significantly increased risk, which was stronger for "at fault" than for
      all crashes. CONCLUSIONS: Abuse of cannabis and cocaine pre-treatment was more
      strongly related to "at fault" crashes than to all crashes. Interaction between
      these substances means that the effects of combined abuse cannot be predicted
      from simple main effects.

PMID- 14693898
TI  - Childhood injuries due to falls from apartment balconies and windows.
AB  - BACKGROUND: Falls from balconies and windows are an important cause of childhood
      injury. This study investigated the circumstances around such falls and attempted
      to identify possible measures for their prevention. POPULATION: Children <15
      years living in Dallas County, Texas. METHODS: Each child treated because of a
      fall from a building in 1997-99 had information about the injury collected, and a
      parent was contacted to obtain further information. For apartment related falls,
      an attempt was made to visit the apartment to measure windows and balcony rails.
      RESULTS: Ninety eight children were injured in falls from buildings during the
      three year period; 39 (40%) were admitted to hospital. Seventy five of the falls
      (77%) involved apartments, and most occurred around noon or evening meal times.
      Among apartment falls, 39 (52%) fell from windows, 34 (45%) from balconies, and
      two (3%) from unknown sites. For more than two thirds of balcony related falls,
      the child fell from between the balcony rails, all of which were spaced more than
      4 inches (10 cm) apart. On-site measurement showed the rails were an average of
      7.5 inches (19 cm) apart; all of these apartments were built before 1984. For
      more than two thirds of window related falls, the window was situated within 2
      feet (61 cm) of the floor. CONCLUSIONS: Two factors are important in falls from
      apartment windows and balconies: balcony rails more than 4 inches (10 cm) apart,
      and windows positioned low to the floor. Current building codes do not apply to
      older apartments, where most of these falls occurred. Nevertheless, these factors
      may be amenable to environmental modifications that may prevent most of these
      falls.

PMID- 14693899
TI  - Vehicle year and the risk of car crash injury.
AB  - OBJECTIVE: To quantify the association between vehicle age and risk of car crash
      injury. DESIGN AND SETTING: Data from a population based case-control study
      conducted in the Auckland region in 1998/99 was used to examine the adjusted risk
      of car crash injury or death due to vehicle age, after controlling for a range of
      known confounders. Cases were all cars involved in crashes in which at least one
      occupant was hospitalized or killed anywhere in the Auckland region, and controls
      were randomly selected cars on Auckland roads. The drivers of the 571 case
      vehicles and 588 control vehicles completed a structured interview. MAIN OUTCOME
      MEASURE: Hospitalisation or death of a vehicle occupant due to car crash injury.
      RESULTS: Vehicles constructed before 1984 had significantly greater chance of
      being involved in an injury crash than those constructed after 1994 (odds ratio
      2.88, 95% confidence interval (CI) 1.20 to 6.91), after adjustment for potential
      confounders. There was also a trend for increasing crash risk with each one year
      increase in vehicle age after adjustment for potential confounders (odds ratio
      1.05, 95% CI 0.99 to 1.11; p = 0.09). CONCLUSION: This study quantifies the
      increased risk of car crash injury associated with older vehicle year and
      confirms this as an important public health issue.

PMID- 14693900
TI  - Washing machine related injuries in children: a continuing threat.
AB  - OBJECTIVE: To describe washing machine related injuries in children in the United
      States. METHODS: Injury data for 496 washing machine related injuries documented
      by the Consumer Product Safety Commission's National Electronic Injury
      Surveillance System and death certificate data files were analyzed. Gender, age,
      diagnosis, body part injured, disposition, location and mechanism of injury were
      considered in the analysis of data. RESULTS: The upper extremities were most
      frequently injured in washing machine related injuries, especially with wringer
      machines. Fewer than 10% of patients required admission, but automatic washers
      accounted for most of these and for both of the deaths. Automatic washer injuries
      involved a wider range of injury mechanism, including 23 children who fell from
      the machines while in baby seats. CONCLUSIONS: Though most injuries associated
      with washing machines are minor, some are severe and devastating. Many of the
      injuries could be avoided with improvements in machine design while others
      suggest a need for increased education of potential dangers and better
      supervision of children if they are allowed access to areas where washing
      machines are operating. Furthermore, washing machines should only be used for
      their intended purpose. Given the limitations of educational efforts to prevent
      injuries, health professionals should have a major role in public education
      regarding these seemingly benign household appliances.

PMID- 14693901
TI  - Evaluation of the ThinkFirst Canada, Smart Hockey, brain and spinal cord injury
      prevention video.
AB  - OBJECTIVE: The ThinkFirst Canada Smart Hockey program is an educational injury
      prevention video that teaches the mechanisms, consequences, and prevention of
      brain and spinal cord injury in ice hockey. This study evaluates knowledge
      transfer and behavioural outcomes in 11-12 year old hockey players who viewed the
      video. DESIGN: Randomized controlled design. SETTING: Greater Toronto Minor
      Hockey League, Toronto Ontario. SUBJECTS: Minor, competitive 11-12 year old male
      ice hockey players and hockey team coaches. INTERVENTIONS: The Smart Hockey video
      was shown to experimental teams at mid-season. An interview was conducted with
      coaches to understand reasons to accept or refuse the injury prevention video.
      MAIN OUTCOME MEASURES: A test of concussion knowledge was administered before,
      immediately after, and three months after exposure to the video. The incidence of
      aggressive penalties was measured before and after viewing the video. RESULTS:
      The number of causes and mechanisms of concussion named by players increased from
      1.13 to 2.47 and from 0.67 to 1.22 respectively. This effect was maintained at
      three months. There was no significant change in control teams. There was no
      significant change in total penalties after video exposure; however, specific
      body checking related penalties were significantly reduced in the experimental
      group. CONCLUSION: This study showed some improvements in knowledge and
      behaviours after a single viewing of a video; however, these findings require
      confirmation with a larger sample to understand the sociobehavioural aspects of
      sport that determine the effectiveness and acceptance of injury prevention
      interventions.

PMID- 14693902
TI  - Shall-issue policy and criminal activity among applicants for permits to carry
      concealed firearms.
AB  - Permits to carry concealed firearms in public (CCW permits) remain controversial.
      A small scale natural experiment with shall-issue CCW permit policy in
      California, a may-issue state, is reported. During the mid-1990s, the chief of
      police of the Sacramento County town of Isleton issued permits to all county
      residents who applied and passed a standard background check. This program
      received national publicity. The incidence of subsequent criminal activity among
      691 persons applying for CCW permits through Isleton's program in 1995 and that
      in a statewide sample of 965 CCW applicants from 1993-94 were compared. Subjects
      were followed up for three years from their application dates. The arrest rates
      for violent crime among Isleton and statewide applicants were 291 and 104 per 100
      000 person-years, respectively (relative risk 2.8, 95% confidence interval 0.7 to
      11.2, p = 0.18). This suggests that a shall-issue policy for CCW permits may
      result in higher rates of violent crime among permit holders, but the results do
      not reach statistical significance; larger studies are needed.

PMID- 14693903
TI  - Reporting of the incidence of hospitalised injuries: numerator issues.
AB  - OBJECTIVES: To examine and discuss the implications on the incidence of
      hospitalised injuries of selecting cases from principal diagnosis field only
      compared with considering all diagnosis fields, the inclusion compared with the
      exclusion of medical injuries, and the impact of identifying multiple admissions.
      METHODS: Analysis of data from the 1999-2000 New South Wales Inpatient Statistics
      Collection, Australia, including an internal linkage of the same dataset.
      RESULTS: Approximately 27.5% of records with a non-injury primary diagnosis
      include a nature of injury diagnosis in a subsequent diagnostic field. This
      figure increased to more than half (53%) of discharges for medical injuries. The
      internal linkage showed that 6.5% of discharges were repeat admissions for the
      same International Classification of Diseases, 10th revision (ICD-10) injury code
      and that 13.8% were repeat admissions for any ICD-10 injury code. The proportions
      of repeat admissions varied according to the type and the mechanism of injury.
      CONCLUSIONS: Selecting hospitalised injury cases from the principal diagnosis
      alone would underestimate medical injury cases as well as other injuries
      occurring in hospital. Repeat admissions should always be considered particularly
      in the case of thermal injuries, self harm, and medical injuries. Due to the
      limitations of data linkage, alternative methods need to be developed to identify
      repeat admissions. Other areas in which further research would be beneficial to a
      more uniform reporting of injury hospitalisations include better identification
      of injuries occurring in hospital, a review of ICD-10 injury codes, and the
      development an ICD-10 based severity measure which can be readily used with
      hospital discharge data.

PMID- 14693904
TI  - Missing cyclists.
AB  - OBJECTIVES: (1) For crashes on a public road, to compare serious cyclist crashes
      involving a motor vehicle with cyclist crashes not involving a motor vehicle, in
      terms of threat to life and length of stay in hospital. (2) To determine the
      proportion of all serious crashes involving cyclists on public roads which are
      recorded by the police. (3) To determine the degree to which under-reporting of
      serious crashes involving cyclists and motor vehicles on public roads is
      associated with various demographic, environmental, and injury factors. STUDY
      DESIGN: Records for the period 1995-99, of cyclists seriously injured on a public
      road and hospitalised were linked to the traffic crash report (TCR) database
      maintained by Land Transport Safety Authority (LTSA). RESULTS: Of the 2925
      cyclist crashes on public roads, only 652 (22%) could be linked to a TCR. Of the
      crashes involving motor vehicles (n = 1033), only 562 (54%) could be linked to
      the LTSA database. Age, ethnicity, injury severity, and cumulative length of stay
      were the only variables that predicted whether hospitalised cycle crash cases
      were more likely to have a corresponding TCR. There were substantial numbers of
      cyclist only crashes which typically are not captured in the TCR database. Nine
      percent of these resulted in serious or worse injury (that is, International
      Classification of Diseases/abbreviated injury scale score of 3+) and 7% resulted
      in hospital stays greater than seven days. CONCLUSION: Greater effort and
      precision needs to be applied to routinely document the burden of cyclist
      crashes, especially cyclist only crashes.

PMID- 14693905
TI  - Helmet laws and cycle use.

PMID- 14693907
TI  - The new traffic law and reduction of alcohol related fatal crashes in Japan.

PMID- 14693906
TI  - Bias when using dead controls to study handgun purchase as a risk factor for
      violent death.

PMID- 14693908
TI  - Effect of N-linked glycosylation on the aspartic proteinase porcine pepsin
      expressed from Pichia pastoris.
AB  - A study was undertaken to examine the effects of N-linked glycosylation on the
      structure-function of porcine pepsin. The N-linked motif was incorporated into
      four sites (two on the N-terminal domain and two on the C-terminal domain), and
      the recombinant protein expressed using Pichia pastoris. All four N-linked
      recombinants exhibited similar secondary and tertiary structure to
      nonglycosylated pepsin, that is, wild type. Similar K(m) values were observed,
      but catalytic efficiencies were approximately one-third for all mutants compared
      with the wild type; however, substrate specificity was not altered. Activation of
      pepsinogen to pepsin occurred between pH 1.0 to 4.0 for wild-type pepsin, whereas
      the glycosylated recombinants activated over a wider range, pH 1.0 to 6.0.
      Glycosylation on the C-terminal domain exhibited similar pH activity profiles to
      nonglycosylated pepsin, and glycosylation on the N-domain resulted in a change in
      activity profile. Overall, glycosylation on the C-domain led to a more global
      stabilization of the structure, which translated into enzymatic stability,
      whereas on the N-domain, an increase in structural stability had little effect on
      enzymatic stability. Finally, glycosylation on the flexible loop region also
      appeared to increase the overall structural stability of the protein compared
      with wild type. It is postulated that the presence of the carbohydrate residues
      added rigidity to the protein structure by reducing conformational mobility of
      the protein, thereby increasing the structural stability of the protein.

PMID- 14693909
TI  - Quaternary solution structures of galectins-1, -3, and -7.
AB  - Galectins are a growing family of animal lectins with functions in growth
      regulation and cell adhesion that bind beta-Gal residues in oligosaccharides.
      Evidence indicates that some of the biological properties of galectins are due to
      their cross-linking activities with multivalent glycoconjugate receptors.
      Therefore determination of the quaternary solution structures of these proteins
      is important in understanding their structure-function properties. The present
      study reports analytical sedimentation velocity and equilibrium data for
      galectins-1, -3, and -7 in the absence and presence of bound LacNAc, the natural
      ligand epitope. Galectin-1 from bovine heart and recombinant human galectin-7
      were found to be stable dimers by both methods. In contrast, recombinant murine
      galectin-3, as well as its proteolytical derived C-terminal domain, are
      predominantly monomeric. The presence of LacNAc at concentrations sufficient to
      fully saturate the proteins had no significant effect on either the weight
      average molecular weight determined by sedimentation equilibrium or the
      hydrodynamic properties determined from sedimentation velocity experiments. These
      results show that binding of a monovalent ligand does not affect oligomerization
      of these galectins.

PMID- 14693910
TI  - Characterization of N-linked oligosaccharides assembled on secretory recombinant
      glucose oxidase and cell wall mannoproteins from the methylotrophic yeast
      Hansenula polymorpha.
AB  - Presently almost no information is available on the oligosaccharide structure of
      the glycoproteins secreted from the methylotrophic yeast Hansenula polymorpha, a
      promising host for the production of recombinant proteins. In this study, we
      analyze the size distribution and structure of N-linked oligosaccharides attached
      to the recombinant glycoprotein glucose oxidase (GOD) and the cell wall
      mannoproteins obtained from H. polymorpha. Oligosaccharide profiling showed that
      the major oligosaccharide species derived from the H. polymorpha-secreted
      recombinant GOD (rGOD) had core-type structures (Man(8-12)GlcNAc(2)). Analyses
      using anti-alpha 1,3-mannose antibody and exoglycosidases specific for alpha 1,2-
      or alpha 1,6-mannose linkages revealed that the mannose outer chains of N-glycans
      on the rGOD have very short alpha 1,6 extensions and are mainly elongated in
      alpha 1,2-linkages without a terminal alpha 1,3-linked mannose addition. The N
      glycans released from the H. polymorpha mannoproteins were shown to contain
      mostly mannose in their outer chains, which displayed almost identical size
      distribution and structure to those of H. polymorpha-derived rGOD. These results
      strongly indicate that the outer chain processing of N-glycans by H. polymorpha
      significantly differs from that by Saccharomyces cerevisiae, thus generating much
      shorter mannose outer chains devoid of terminal alpha 1,3-linked mannoses.

PMID- 14693911
TI  - Site-specific N-glycosylation of chicken serum IgG.
AB  - Avian serum immunoglobulin (IgG or IgY) is functionally equivalent to mammalian
      IgG but has one additional constant region domain (CH2) in its heavy (H) chain.
      In chicken IgG, each H-chain contains two potential N-glycosylation sites located
      on CH2 and CH3 domains. To clarify characteristics of N-glycosylation on avian
      IgG, we analyze N-glycans from chicken serum IgG by derivatization with 2
      aminopyridine (PA) and identified by HPLC and MALDI-TOF-MS. There were two types
      of N-glycans: (1) high-mannose-type oligosaccharides (monoglucosylated 26.8%,
      others 10.5%) and (2) biantennary complex-type oligosaccharides (neutral, 29.9%;
      monosialyl, 29.3%; disialyl, 3.7%) on molar basis of total N-glycans. To
      investigate the site-specific localization of different N-glycans, chicken serum
      IgG was digested with papain and separated into Fab [containing variable regions
      (VH + VL) + CH1 + CL] and Fc (containing CH3 + CH4) fragments. Con A stained only
      Fc (CH3 + CH4) and RCA-I stained only Fab fractions, suggesting that high-mannose
      type oligosaccharides were located on Fc (CH3 + CH4) fragments, and variable
      regions of Fab contains complex-type N-glycans. MS analysis of chicken IgG
      glycopeptides revealed that chicken CH3 domain (structurally equivalent to
      mammalian CH2 domain) contained only high-mannose-type oligosaccharides, whereas
      chicken CH2 domain contained only complex-type N-glycans. The N-glycosylation
      pattern on avian IgG is more analogous to that in mammalian IgE than IgG,
      presumably reflecting the structural similarity to mammalian IgE.

PMID- 14693912
TI  - Biochemical and molecular characterization of galectins from zebrafish (Danio
      rerio): notochord-specific expression of a prototype galectin during early
      embryogenesis.
AB  - Galectins are a family of beta-galactoside-binding lectins that on synthesis are
      either translocated into the nucleus or released to the extracellular space.
      Their developmentally regulated expression, extracellular location, and affinity
      for extracellular components (such as laminin and fibronectin) suggest a role in
      embryonic development, but so far this has not been unequivocally established.
      Zebrafish constitute an ideal model for developmental studies because of their
      external fertilization, transparent embryos, rapid growth, and availability of a
      large collection of mutants. As a first step in addressing the biological roles
      in zebrafish embryogenesis, we identified and characterized members of the three
      galectin types: three protogalectins (Drgal1-L1, Drgal1-L2, Drgal1-L3), one
      chimera galectin (Drgal3), and one tandem-repeat galectin (Drgal9-L1). Like
      mammalian prototype galectin-1, Drgal1-L2 preferentially binds to N
      acetyllactosamine. Genomic structure of Drgal1-L2 revealed four exons, with the
      exon-intron boundaries conserved with the mammalian galectin-1. Interestingly,
      this gene also encodes an alternatively spliced form of Drgal1-L2 that lacks
      eight amino acids near the carbohydrate-binding domain. Zebrafish galectins
      exhibited distinct patterns of temporal expression during embryo development.
      Drgal1-L2 is expressed postbud stage, and its expression is strikingly specific
      to the notochord. In contrast, Drgal1-L1 is expressed maternally in the oocytes.
      Drgal1-L3, Drgal3, and Drgal9-L1 are expressed both maternally and zygotically,
      ubiquitously in the adult tissues. The distinct temporal and spatial patterns of
      expression of members of the zebrafish galectin repertoire suggest that each may
      play distinct biological roles during early embryogenesis.

PMID- 14693913
TI  - Characterization of N- and O-linked glycosylation of recombinant human bile salt
      stimulated lipase secreted by Pichia pastoris.
AB  - Recombinant human bile salt-stimulated lipase (hBSSL) was expressed in and
      secreted by Pichia pastoris, an organism exploited for the large-scale production
      of recombinant (glyco)proteins by bioprocessing technology. The 76.3-kDa
      glycoprotein was associated with 75-80 Man and a small amount of GlcNAc. hBSSL
      has one N-glycosylation site at Asn187, which was 38-40% occupied with a
      Man(10)GlcNAc(2) structure defined previously in Pichia as the oligosaccharide
      lipid form of Man(9)GlcNAc(2) trimmed of the middle-arm terminal alpha 1,2-Man
      and elongated with Man alpha 1,2Man alpha 1,6-disaccharide attached to the lower
      arm core alpha 1,3-Man (Trimble et al. [1991], J. Biol. Chem., 266, 22807-22817).
      The C-terminal 192 residues of hBSSL contain 16 Pro-rich 11-amino-acid repeats,
      which include 32 Ser/Thr residues as potential O-glycosylation sites. Using hBSSL
      as a platform to study Pichia's O-glycosylation capabilities, we found that
      nearly all of these sites were occupied by mannose-containing O-glycans, whose
      structures, after beta-elimination and purification, were assigned by (1)H NMR
      and, in some cases, by linkage-specific exoglycosidases and methylation analysis.
      The most abundant O-glycan was alpha 1,2-mannobiitol (55%), followed by alpha 1,2
      mannotriitol (16%) and mannitol (10%) and a lesser amount was alpha 1,2
      mannotetraitol. Unexpectedly, Man(5) and Man(6) O-glycans were present, which had
      the structure Man beta 1,2Man beta 1,2Man alpha 1,2(Man alpha 1,2)(1,2)mannitol.
      Also a small amount of a phosphorylated Man(6) O-glycan was characterized by
      MALDI-TOF MS postsource decay analysis as having the reducing-end mannitol
      disubstituted with a glycosidically linked phosphorylated Man and an unbranched
      Man(4) polymer elongated from a different mannitol carbon. This is the first
      report of the synthesis of beta-Man- and phosphate-containing O-linked
      constituents on glycoproteins synthesized by P. pastoris.

PMID- 14693914
TI  - Diffusion ordered spectroscopy as a complement to size exclusion chromatography
      in oligosaccharide analysis.
AB  - A series of N-acetyl-chitooligosaccharides (GlcNAc)(1-6) have been studied by a
      nuclear magnetic resonance (NMR) method, diffusion ordered spectroscopy (DOSY).
      DOSY has also been applied to two additional synthetic related oligosaccharides
      [GlcNH(2)-(GlcNAc)(4) and GlcNH(2)-(GlcNAc)(2)-GlcNAcSO(3)Na]. A plot of the log
      of the determined diffusion coefficients (logD) of (GlcNAc)(n) versus the log of
      molecular weight was linear (6 points, R(2) = 0.995). The molecular weights of
      the two synthetic chitin derivatives could be estimated to within 10% error. The
      processed NMR data of all the chitooligosaccharides was also plotted in a
      polyacrylamide gel-like format to aid visual interpretation. Moreover, the logD
      value of the NMR signal resonances of a chitin-binding protein (hevein) changed
      as a function of a given titrated ligand, (GlcNAc)(6). Evidence for a 2:1
      hevein:(GlcNAc)(6) complex is detected by DOSY at high hevein:(GlcNAc)(6) ratios.
      This data is consistent with published analytical ultracentrifugation and
      isothermal titration calorimetry data. A 1:1 complex is preferred at higher
      ligand concentrations. DOSY can complement size exclusion chromatography in
      carbohydrate research with the advantage that oligosaccharides are more readily
      detected by NMR.

PMID- 14693915
TI  - A uniquely human consequence of domain-specific functional adaptation in a sialic
      acid-binding receptor.
AB  - Most mammalian cell surfaces display two major sialic acids (Sias), N
      acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). Humans
      lack Neu5Gc due to a mutation in CMP-Neu5Ac hydroxylase, which occurred after
      evolutionary divergence from great apes. We describe an apparent consequence of
      human Neu5Gc loss: domain-specific functional adaptation of Siglec-9, a member of
      the family of sialic acid-binding receptors of innate immune cells designated the
      CD33-related Siglecs (CD33rSiglecs). Binding studies on recombinant human Siglec
      9 show recognition of both Neu5Ac and Neu5Gc. In striking contrast, chimpanzee
      and gorilla Siglec-9 strongly prefer binding Neu5Gc. Simultaneous probing of
      multiple endogenous CD33rSiglecs on circulating blood cells of human, chimp, or
      gorilla suggests that the binding differences observed for Siglec-9 are
      representative of multiple CD33rSiglecs. We conclude that Neu5Ac-binding ability
      of at least some human CD33rSiglecs is a derived state selected for following
      loss of Neu5Gc in the hominid lineage. These data also indicate that endogenous
      Sias (rather than surface Sias of bacterial pathogens) are the functional ligands
      of CD33rSiglecs and suggest that the endogenous Sia landscape is the major factor
      directing evolution of CD33rSiglec binding specificity. Exon-1-encoded Sia
      recognizing domains of human and ape Siglec-9 share only approximately 93-95%
      amino acid identity. In contrast, the immediately adjacent intron and exon 2 have
      the approximately 98-100% identity typically observed among these species.
      Together, our findings suggest ongoing adaptive evolution specific to the Sia
      binding domain, possibly of an episodic nature. Such domain-specific divergences
      should also be considered in upcoming comparisons of human and chimpanzee
      genomes.

PMID- 14693916
TI  - Biosynthesis of 6-deoxyhexose glycans in bacteria.
AB  - After the breakthroughs in genomic sequencing, one of the next challenges remains
      to understand the molecular biology of other classes of biomolecules, such as
      protein and lipids, many of which carry specific glycomodification when mediating
      their biological functions. This review focuses on the 6-deoxyhexose biosynthesis
      of cell surface glycans of three Gram-negative pathogens, Helicobacter pylori,
      Pseudomonas aeruginosa, and Actinobacillus actinomycetemcomitans serotype a. 6
      Deoxysugars are important functional components of cell surface glycans, and
      their biosynthetic pathways might be suitable targets for novel interventions of
      antibacterial chemotherapy.

PMID- 14693917
TI  - Galectin-1 induces astrocyte differentiation, which leads to production of brain
      derived neurotrophic factor.
AB  - Brain-derived neurotrophic factor (BDNF) is a neuroprotective polypeptide that is
      thought to be responsible for neuron proliferation, differentiation, and
      survival. An agent that enhances production of BDNF is expected to be useful for
      the treatment of neurodegenerative diseases. Here we report that galectin-1, a
      member of the family of beta-galactoside binding proteins, induces astrocyte
      differentiation and strongly inhibits astrocyte proliferation, and then the
      differentiated astrocytes greatly enhance their production of BDNF. Induction of
      astrocyte differentiation and BDNF production by an endogenous mammalian lectin
      may be a new mechanism for preventing neuronal loss after injury.

PMID- 14693921
TI  - Diagnosis and classification of diabetes mellitus.

PMID- 14693922
TI  - Screening for type 2 diabetes.

PMID- 14693923
TI  - Standards of medical care in diabetes.

PMID- 14693924
TI  - Nutrition principles and recommendations in diabetes.

PMID- 14693925
TI  - Prevention or delay of type 2 diabetes.

PMID- 14693926
TI  - Diabetes nutrition recommendations for health care institutions.

PMID- 14693927
TI  - Physical activity/exercise and diabetes.

PMID- 14693928
TI  - Preventive foot care in diabetes.

PMID- 14693929
TI  - Hypertension management in adults with diabetes.

PMID- 14693930
TI  - Dyslipidemia management in adults with diabetes.

PMID- 14693931
TI  - Aspirin therapy in diabetes.

PMID- 14693932
TI  - Smoking and diabetes.

PMID- 14693933
TI  - Preconception care of women with diabetes.

PMID- 14693934
TI  - Nephropathy in diabetes.

PMID- 14693935
TI  - Retinopathy in diabetes.

PMID- 14693936
TI  - Gestational diabetes mellitus.

PMID- 14693937
TI  - Tests of glycemia in diabetes.

PMID- 14693938
TI  - Hyperglycemic crises in diabetes.

PMID- 14693939
TI  - Hospital admission guidelines for diabetes.

PMID- 14693940
TI  - Bedside blood glucose monitoring in hospitals.

PMID- 14693941
TI  - Pancreas transplantation in type 1 diabetes.

PMID- 14693942
TI  - Insulin administration.

PMID- 14693943
TI  - Continuous subcutaneous insulin infusion.

PMID- 14693944
TI  - Influenza and pneumococcal immunization in diabetes.

PMID- 14693945
TI  - Diabetes management in correctional institutions.

PMID- 14693946
TI  - Diabetes care in the school and day care setting.

PMID- 14693947
TI  - Diabetes care at diabetes camps.

PMID- 14693948
TI  - Concurrent care.

PMID- 14693949
TI  - Prevention of type 1 diabetes.

PMID- 14693950
TI  - Hypoglycemia and employment/licensure.

PMID- 14693951
TI  - Unproven therapies.

PMID- 14693952
TI  - Third-party reimbursement for diabetes care, self-management education, and
      supplies.

PMID- 14693955
TI  - National standards for diabetes self-management education.

PMID- 14693957
TI  - Improving diabetes care in midwest community health centers with the health
      disparities collaborative.
AB  - OBJECTIVE: To evaluate the Diabetes Health Disparities Collaborative, an
      initiative by the Bureau of Primary Health Care to reduce health disparities and
      improve the quality of diabetes care in community health centers. RESEARCH DESIGN
      AND METHODS: One year before- after trial. Beginning in 1998, 19 Midwestern
      health centers undertook a diabetes quality improvement initiative based on a
      model including rapid Plan-Do-Study-Act cycles from the continuous quality
      improvement field; a Chronic Care Model emphasizing patient self-management,
      delivery system redesign, decision support, clinical information systems,
      leadership, health system organization, and community outreach; and collaborative
      learning sessions. We reviewed charts of 969 random adults for American Diabetes
      Association standards, surveyed 79 diabetes quality improvement team members, and
      performed qualitative interviews. RESULTS: The performance of several key
      processes of care assessed by chart review increased, including rates of HbA(1c)
      measurement (80-90%; adjusted odds ratio 2.1, 95% CI 1.6-2.8), eye examination
      referral (36-47%; 1.6, 1.1-2.3), foot examination (40-64%; 2.7, 1.8-4.1), and
      lipid assessment (55-66%; 1.6, 1.1-2.3). Mean value of HbA(1c) tended to improve
      (8.5-8.3%; difference -0.2, 95% CI -0.4 to 0.03). Over 90% of survey respondents
      stated that the Diabetes Collaborative was worth the effort and was successful.
      Major challenges included needing more time and resources, initial difficulty
      developing computerized patient registries, team and staff turnover, and
      occasional need for more support by senior management. CONCLUSIONS: The Health
      Disparities Collaborative improved diabetes care in health centers in 1 year.

PMID- 14693958
TI  - Opportunistic screening for diabetes in routine clinical practice.
AB  - OBJECTIVE: Since 1997, the American Diabetes Association has recommended that
      nondiabetic individuals >/=45 years of age be screened for diabetes at least
      every 3 years. We sought to characterize the frequency, methods, and results of
      diabetes screening in routine clinical practice. RESEARCH DESIGN AND METHODS: We
      studied opportunistic screening in nondiabetic members of a health maintenance
      organization >/=45 years of age who were assigned to a large, integrated,
      academic health care delivery system. Screening was defined as the first glucose,
      HbA(1c), or oral glucose tolerance test (OGTT) performed between 1 January 1998
      and 31 December 2000. Chart review was performed to determine the prevalence of
      diabetes risk factors and to describe follow-up. RESULTS: Of 8,286 nondiabetic
      patients >/=45 years of age, 69% (n = 5,752) were screened. The frequency of
      screening was greater in patients with one or more primary care visits and
      increased with age. Women were more likely to be screened than men, and patients
      with at least one diabetes risk factor were more likely to be screened than those
      without risk factors. Random plasma glucose was the most common screening test
      (95%). Four percent (n = 202) of those screened had abnormal results. Only 38% (n
      = 77) of those with abnormal results received appropriate follow-up, and 17% (n =
      35) were diagnosed with diabetes within 6 months of screening. The yield of
      screening was very low (0.6%, 35 of 5,752). CONCLUSIONS: Despite frequent
      screening and appropriate targeting of high-risk patients, follow-up of patients
      with abnormal results is uncommon and the yield of screening is low.
      Interventions are needed to help physicians recognize and provide appropriate
      follow-up for patients with potentially abnormal random glucose levels.

PMID- 14693959
TI  - Clinical decisions regarding HbA1c results in primary care: a report from CaReNet
      and HPRN.
AB  - OBJECTIVE: To describe decisions made by primary care providers on elevated
      HbA(1c) results and their reasons for not intensifying therapy. RESEARCH DESIGN
      AND METHODS: In this cross-sectional study, a provider survey was administered in
      two practice-based research networks when HbA(1c) results were reviewed on all
      nonpregnant patients >18 years old with type 2 diabetes. Univariate and Mantel
      Hantel analyses assessed associations between patient characteristics and
      clinical decisions. RESULTS: A total of 483 surveys were completed by at least 88
      providers at 19 clinics. Most patients were female (62.5%), mean age was 60
      years, and 28.6% were Hispanic. The overall action rate on HbA(1c) results >/=7%
      (n = 294) was 70.7%. Patients who were black or had Medicare without medication
      insurance had lower rates of action on HbA(1c) >/=7 and >/=8%, respectively (P <
      0.05). The most common reasons providers reported for inaction were "patient
      improving/doing well," "competing demands," and "hypoglycemic risk." CONCLUSIONS:
      Primary care providers generally adhere to national glycemic control guidelines,
      although there may be disparities in black patients and patients without
      medication insurance coverage. A variety of reasons were given when control was
      not intensified.

PMID- 14693960
TI  - Glycemic control from 1988 to 2000 among U.S. adults diagnosed with type 2
      diabetes: a preliminary report.
AB  - OBJECTIVE: To describe the changes in demographics, antidiabetic treatment, and
      glycemic control among the prevalent U.S. adult diagnosed type 2 diabetes
      population between the National Health and Nutrition Examination Survey (NHANES)
      III (1988-1994) and the initial release of NHANES 1999-2000. RESEARCH DESIGN AND
      METHODS: The study population was derived from NHANES III (n = 1,215) and NHANES
      1999-2000 (n = 372) subjects who reported a diagnosis of type 2 diabetes with
      available data on diabetes medication and HbA(1c). Four therapeutic regimens were
      defined: diet only, insulin only, oral antidiabetic drugs (OADs) only, or OADs
      plus insulin. Multiple logistic regression was used to examine changes in
      antidiabetic regimens and glycemic control rates over time, adjusted for
      demographic and clinical risk factors. The outcome measure for glycemic control
      was HbA(1c). Glycemic control rates were defined as the proportion of type 2
      diabetic patients with HbA(1c) level <7%. RESULTS: Dietary treatment in
      individuals with diabetes decreased as the sole therapy from 27.4 to 20.2%
      between the surveys. Insulin use also decreased from 24.2 to 16.4%, while those
      on OADs only increased from 45.4 to 52.5%. Combination of OADs and insulin
      increased from 3.1 to 11.0%. Glycemic control rates declined from 44.5% in NHANES
      III (1988-1994) to 35.8% in NHANES 1999-2000. CONCLUSIONS: Treatment regimens
      among U.S. adults diagnosed with type 2 diabetes have changed substantially over
      the past 10 years. However, a decrease in glycemic control rates was also
      observed during this time period. This trend may contribute to increased rates of
      macrovascular and microvascular diabetic complications, which may impact health
      care costs. Our data support the public health message of implementation of
      early, aggressive management of diabetes.

PMID- 14693961
TI  - Inflammation and glucose intolerance: a prospective study of gestational diabetes
      mellitus.
AB  - OBJECTIVE: Increased leukocyte count is a marker of inflammation that has been
      associated with the development of type 2 diabetes in prospective studies.
      Although gestational diabetes mellitus (GDM) and type 2 diabetes share certain
      pathophysiological mechanisms, few studies have examined inflammation and risk of
      GDM. RESEARCH DESIGN AND METHODS: We prospectively examined routine leukocyte
      counts collected at the first prenatal visit in a cohort of 2,753 nulliparous
      euglycemic women, 98 (3.6%) of whom were later diagnosed with GDM. Subjects were
      divided into quartiles of leukocyte count, and the results of third-trimester
      glucose screening tests and the incidence of GDM among these quartiles were
      compared. Logistic regression was used to calculate univariate and multivariable
      adjusted relative risks (RRs) of GDM according to leukocyte quartiles. RESULTS:
      Leukocyte counts were increased among women who subsequently developed GDM
      compared with those who remained free of GDM (10.5 +/- 2.2 vs. 9.2 +/- 2.2 x
      10(3) cells/ml; P < 0.01). There was a linear increase in postloading mean
      glucose levels (P for trend <0.01), the area under the glucose tolerance test
      curves (P for trend <0.01), and the incidence of GDM (quartile 1, 1.1; quartile
      2, 2.5; quartile 3, 4.2; and quartile 4, 6.4%; P for trend <0.01) with increasing
      leukocyte quartiles. In the multivariable-adjusted analysis, the linear trend in
      the RR of GDM with increasing leukocyte quartiles remained statistically
      significant (quartile 1, reference; quartile 2, RR 2.3 [95% CI 0.9-5.7]; quartile
      3, 3.3 [1.4-7.8]; quartile 4, 4.9 [2.1-11.2]; P for trend <0.01). CONCLUSIONS:
      Increased leukocyte count early in pregnancy is independently and linearly
      associated with the results of GDM screening tests and the risk of GDM. Although
      overlap in the leukocyte count distributions precludes it from being a clinically
      useful biomarker, these data suggest that inflammation is associated with the
      development of GDM and may be another pathophysiological link between GDM and
      future type 2 diabetes.

PMID- 14693962
TI  - Acute effects of different intensities of exercise in
      normoalbuminuric/normotensive patients with type 1 diabetes.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of exercise
      occurrence and intensity on albumin excretion in normotensive, normoalbuminuric
      patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Eighteen patients
      (aged 29 +/- 2 years, duration of diabetes 14 +/- 2 years, blood pressure 120 +/-
      2/74 +/- 1 mmHg, HbA(1c) 7.0 +/- 0.2% [mean +/- SE]) without microalbuminuria,
      hypertension, or anti-angiotensin II therapy participated in two exercise studies
      in a clinical research center. Exercise intensities were defined as moderate (50%
      heart rate reserve [HRR]) and intense (75% HRR) and were performed in random
      order. Subjects collected urine for albumin determination on the days before and
      after exercise. On the day of exercise, subjects exercised for 30 min on a
      treadmill at the assigned intensity. Timed urine collections were obtained over
      the day. Blood pressures were measured using an ambulatory blood pressure
      monitor. RESULTS: Moderate exercise demonstrated no changes in albumin excretion.
      Intense exercise demonstrated a significant increase in albumin excretion during
      the first 4 h compared with the rest of the day (P = 0.03) but returned to normal
      thereafter. Albumin excretion did not exceed normal levels throughout the study.
      There was no difference in albumin excretion surrounding days of intense
      exercise. Ambulatory blood pressures demonstrated nocturnal dipping after
      moderate and intense exercise (P < 0.001). CONCLUSIONS: We have demonstrated that
      normotensive, normoalbuminuric patients without anti-angiotensin II therapy do
      not have elevated albumin excretion following exercise intensities experienced by
      most patients with type 1 diabetes.

PMID- 14693963
TI  - Effects of moderate weight loss and orlistat on insulin resistance, regional
      adiposity, and fatty acids in type 2 diabetes.
AB  - OBJECTIVE: Moderate weight loss is recommended for overweight and obese patients
      with type 2 diabetes, and conjunctive use of weight loss medication has been
      advocated. The current study examined weight loss-dependent and -independent
      effects of the intestinal lipase inhibitor orlistat at 6 months of treatment,
      using behavioral intervention (Int) combined with randomized, double-blinded,
      placebo (P)-controlled treatment with orlistat (O). RESEARCH DESIGN AND METHODS:
      Metabolic control, insulin sensitivity (IS), regional fat distribution, and fat
      content in liver and muscle were measured in 39 volunteers with type 2 diabetes
      in whom all antidiabetic medication was withdrawn 1 month preceding
      randomization. Weight loss was equivalent in the Int+O and Int+P groups,
      respectively (-10.3 +/- 1.3 vs. -8.9 +/- 1.1%), and there were identical
      decreases in visceral adipose tissue (VAT), fat mass (FM), thigh adiposity, and
      hepatic steatosis. RESULTS: Weight loss resulted in substantial improvement (P <
      0.001) in HbA(1c) (-1.6 +/- 0.3 vs. -1.0 +/- 0.4%; NS between groups). IS
      improved significantly more with orlistat (Delta2.2 +/- 0.4 vs. Delta1.2 +/- 0.4
      mg. min(-1). kg(-1) fat-free mass [FFM]; P < 0.05), and plasma free fatty acid
      (FFA) levels were strongly correlated with IS (r = 0.56; P < 0.001). Orlistat
      caused greater reductions in fasting plasma FFA (Delta-154 +/- 22 vs. Delta-51 +/
      33 micro mol/l; P < 0.05), insulin-suppressed FFA (Delta-119 +/- 23 vs. Delta-87
      +/- 34 micro mol/l; P < 0.05), and fasting plasma glucose (FPG; -62 +/- 9 vs. -32
      +/- 8 mg/dl; P = 0.02). Changes in HbA(1c) were correlated with DeltaIS (r = 
      0.41; P < 0.01) but not with weight loss per se. CONCLUSIONS: At equivalent
      weight loss, conjunctive use of orlistat resulted in greater improvement in FFA
      levels and IS.

PMID- 14693964
TI  - Favorable effects of pioglitazone and metformin compared with gliclazide on
      lipoprotein subfractions in overweight patients with early type 2 diabetes.
AB  - OBJECTIVE: To compare effects of different oral hypoglycemic drugs as first-line
      therapy on lipoprotein subfractions in type 2 diabetes. RESEARCH DESIGN AND
      METHODS: Sixty overweight type 2 diabetic patients not on lipid-lowering therapy
      were randomized to metformin, pioglitazone, or gliclazide after a 3-month dietary
      run-in. Drug doses were uptitrated for 3 months to optimize glycemia and were
      kept fixed for a further 3 months. LDL subfractions (LDL(1), LDL(2), and LDL(3))
      were prepared by density gradient ultracentrifugation at randomization and study
      end. Triglycerides, cholesterol, total protein, and phospholipids were measured
      and mass of subfractions calculated. HDL subfractions were prepared by
      precipitation. The primary end point was change in proportion of LDL as LDL(3).
      RESULTS: HbA(1c), triglycerides, glucose, and cholesterol were comparable across
      groups at baseline and over time. LDL(3) mass and the LDL(3)-to-LDL ratio fell
      with pioglitazone (LDL(3) mass 36.2 to 28.0 mg/dl, P < 0.01; LDL(3)-to-LDL
      19.2:13.3%, P < 0.01) and metformin (42.7 to 31.5 mg/dl, P < 0.01; 21.3:16.2%, P
      < 0.01, respectively) with no change on gliclazide. LDL(3) reductions were
      associated with reciprocal LDL(1) increases. Changes were independent of BMI,
      glycemic control, and triglycerides. Total HDL cholesterol increased on
      pioglitazone (1.28 to 1.36 mmol/l, P = 0.02) but not gliclazide (1.39 to 1.37
      mmol/l, P = NS) or metformin (1.26 to 1.18 mmol/l, P = NS), largely due to an
      HDL(2) increase (0.3 to 0.4 mmol/l, P < 0.05). HDL(3) cholesterol fell on
      metformin (0.9 to 0.85 mmol/l, P < 0.01). On pioglitazone and metformin, the
      HDL(2)-to-HDL(3) ratio increased compared with no change on gliclazide.
      CONCLUSIONS: For the same improvement in glycemic control, pioglitazone and
      metformin produce favorable changes in HDL and LDL subfractions compared with
      gliclazide in overweight type 2 diabetic patients. Such changes may be associated
      with reduced atherosclerosis risk and may inform the choice of initial oral
      hypoglycemic agent.

PMID- 14693965
TI  - Effect of weight loss on cardiac synchronization and proinflammatory cytokines in
      premenopausal obese women.
AB  - OBJECTIVE: Obesity is an important risk factor for heart failure in both women
      and men. Dyssynchrony between right and left ventricular contraction and
      relaxation has been identified as an independent predictor of heart failure. We
      examined the relationship of ventricular synchronization abnormalities with the
      concentration of proinflammatory cytokines in obese women at baseline and after
      sustained weight loss. RESEARCH DESIGN AND METHODS: Echocardiographic parameters
      of ventricular dyssynchrony, circulating levels of tumor necrosis factor (TNF)
      alpha, interleukin (IL)-6, IL-18, and C-reactive protein (CRP) were investigated
      in 67 healthy, premenopausal obese women and 40 age-matched normal-weight women.
      RESULTS: Compared with nonobese women, obese women had increased concentrations
      of CRP (P < 0.01), TNF-alpha (P < 0.01), IL-6 (P < 0.01), and IL-18 (P < 0.01).
      Moreover, obese women had a higher myocardial performance index (P < 0.02) and
      lower transmitral Doppler flow (P < 0.05), pulmonary venous flow analysis (P <
      0.02), and ejection fraction (P < 0.05), indicating ventricular dyssynchrony.
      Concentrations of CRP, TNF-alpha, and IL-6 were related to anthropometric indexes
      of obesity and to echocardiographic parameters of ventricular dyssynchrony. After
      1 year of a multidisciplinary program of weight reduction, obese women lost at
      least 10% of their original weight. This was associated with reduction of
      cytokine (P < 0.01) and CRP (P < 0.02) concentrations and with improvement of
      echocardiographic parameters of ventricular dyssynchrony, which correlated with
      changes in adiposity, particularly visceral adiposity. CONCLUSIONS: In obese
      women, ventricular dyssynchrony correlates with body fat, possibly through
      inappropriate secretion of cytokines. Weight loss represents a safe method for
      downregulating the inflammatory state and ameliorating cardiac function in obese
      women.

PMID- 14693966
TI  - Low synthesis and high absorption of cholesterol characterize type 1 diabetes.
AB  - OBJECTIVE: Streptozotocin-induced type 1 diabetes in experimental animals
      inhibits cholesterol synthesis and increases cholesterol absorption. In contrast
      to human type 2 diabetes, virtually no information is available on cholesterol
      synthesis and absorption in type 1 diabetes. RESEARCH DESIGN AND METHODS: We
      studied the variables of cholesterol metabolism in 27 patients with type 1
      diabetes and in 10 patients with type 2 diabetes matched for body weight, using
      cholesterol precursor sterol ratios to cholesterol as surrogate markers of
      synthesis, and those of cholestanol and plant sterols of cholesterol absorption.
      Glucose control was good in all subjects. RESULTS: Total and HDL cholesterol and
      LDL triglycerides were higher in type 2 than in type 1 diabetes. Serum sterols,
      measured also in VLDL, intermediate-density lipoprotein (IDL), LDL, and HDL, were
      transported up to >90% by LDL and HDL in type 1 diabetes. The ratios of all
      absorption sterols in serum and in each lipoprotein were higher, and those of the
      synthesis markers, especially cholestenol and lathosterol, were lower in type 1
      than in type 2 diabetes. CONCLUSIONS: In contrast to type 2 diabetes, the
      findings in type 1 diabetes could be related to low expression of ABC G/5 G/8
      genes, resulting in high absorption of cholesterol and sterols in general and low
      synthesis of cholesterol.

PMID- 14693967
TI  - Dietary magnesium intake in relation to plasma insulin levels and risk of type 2
      diabetes in women.
AB  - OBJECTIVE: Higher intake of magnesium appears to improve glucose and insulin
      homeostasis; however, there are sparse prospective data on the association
      between magnesium intake and incidence of type 2 diabetes. RESEARCH DESIGN AND
      METHODS: In the Women's Health Study, a cohort of 39,345 U.S. women aged >/=45
      years with no previous history of cardiovascular disease, cancer, or type 2
      diabetes completed validated semiquantitative food frequency questionnaires in
      1993 and were followed for an average of 6 years. We used Cox proportional hazard
      models to estimate multivariate relative risks (RRs) of type 2 diabetes across
      quintiles of magnesium intake compared with the lowest quintile. In a sample of
      349 apparently healthy women from this study, we measured plasma fasting insulin
      levels to examine their relation to magnesium intake. RESULTS: During 222,523
      person-years of follow-up, we documented 918 confirmed incident cases of type 2
      diabetes. There was a significant inverse association between magnesium intake
      and risk of type 2 diabetes, independent of age and BMI (P = 0.007 for trend).
      After further adjustment for physical activity, alcohol intake, smoking, family
      history of diabetes, and total calorie intake, the multivariate-adjusted RRs of
      diabetes from the lowest to highest quintiles of magnesium intake were attenuated
      at 1.0, 1.06, 0.81, 0.86, and 0.89 (P = 0.05 for trend). Among women with BMI
      >/=25 kg/m2, the inverse trend was significant; multivariate-adjusted RRs were
      1.0, 0.96, 0.76, 0.84, and 0.78 (P = 0.02 for trend). Multivariate-adjusted
      geometric mean insulin levels for overweight women in the lowest quartile of
      magnesium intake was 53.5 compared with 41.5 pmol/l among those at the highest
      quartile (P = 0.03 for trend). CONCLUSIONS: These findings support a protective
      role of higher intake of magnesium in reducing the risk of developing type 2
      diabetes, especially in overweight women.

PMID- 14693968
TI  - Type 2 diabetes prevalence in Asian Americans: results of a national health
      survey.
AB  - OBJECTIVE: Asians are thought to be at high risk for diabetes, yet there is
      little population-based information about diabetes in Asian Americans. The
      purpose of this study was to directly compare the prevalence of type 2 diabetes
      in Asian Americans with other racial and ethnic groups in the U.S. using data
      from the 2001 Behavioral Risk Factor Surveillance System (BRFSS). RESEARCH DESIGN
      AND METHODS: The BRFSS is a population-based telephone survey of the health
      status and health behaviors of Americans in all 50 states, Guam, Puerto Rico, and
      the U.S. Virgin Islands. Subjects included 3,071 Asians, 12,561 blacks, 12,153
      Hispanics, 2,299 Native Americans, 626 Pacific Islanders, and 129,116 non
      Hispanic whites aged >/=30 years. Subjects who reported a physician-diagnosis of
      diabetes were considered to have type 2 diabetes unless they were diagnosed
      before age 30. RESULTS: Compared with whites, odds ratios (95% CIs) for diabetes,
      adjusted for age and sex, were 1.0 (0.7-1.4) for Asians, 2.3 (2.1-2.6) for
      blacks, 2.0 (1.8-2.3) for Hispanics, 2.2 (1.6-2.9) for Native Americans, and 3.1
      (1.4-6.8) for Pacific Islanders. Results adjusted for BMI, age, and sex were 1.6
      (1.2-2.3) for Asians, 1.9 (1.7-2.2) for blacks, 1.9 (1.6-2.1) for Hispanics, 1.8
      (1.3-2.5) for Native Americans, and 3.0 (1.4-6.7) for Pacific Islanders.
      CONCLUSIONS: Similar proportions of Asian and non-Hispanic white Americans report
      having diabetes, but after accounting for the lower BMI of Asians, the adjusted
      prevalence of diabetes is 60% higher in Asian Americans.

PMID- 14693969
TI  - Diabetes and outcome of community-acquired pneumococcal bacteremia: a 10-year
      population-based cohort study.
AB  - OBJECTIVE: Patients with diabetes may carry a higher case fatality of invasive
      pneumococcal infection compared with nondiabetic patients due to decreased
      immunity, risk of metabolic derangement, or angiopathy. We conducted a population
      based cohort study to assess the impact of diabetes on mortality within 90 days
      in patients with pneumococcal bacteremia. RESEARCH DESIGN AND METHODS: All
      patients with community-acquired pneumococcal bacteremia in North Jutland County,
      Denmark, from January 1992 to December 2001 were retrieved from the County
      Bacteremia Registry. Using civil registry numbers, patients with diabetes were
      identified by record linkage with the County Prescription Database (for
      antidiabetic drugs) and the County Hospital Discharge Registry. Mortality within
      90 days was determined through the Central Population Registry. Mortality rates
      were compared for diabetic and nondiabetic patients and adjusted for sex, age,
      and comorbidity. RESULTS: Among 628 patients aged >15 years with community
      acquired pneumococcal bacteremia, 63 (10.0%) had diabetes. The diabetic patients
      were slightly older (median age 71.7 years) than the nondiabetic patients (67.0
      years), and the proportion of patients with comorbidity was higher in the
      diabetic group (59 vs. 46%). Mortality in diabetic patients compared with
      nondiabetic patients was 11.1 vs. 16.5% after 30 days and 16.0 vs. 19.5% after 90
      days, respectively. After adjustment for sex, age, and comorbidity, the mortality
      rate ratio for diabetic patients was 0.6 (95% CI 0.3-1.2) compared with the
      nondiabetic patients. CONCLUSIONS: Diabetic patients with community-acquired
      pneumococcal bacteremia appear not to have a higher case fatality than
      nondiabetic patients.

PMID- 14693970
TI  - Fasting plasma free fatty acids and risk of type 2 diabetes: the atherosclerosis
      risk in communities study.
AB  - OBJECTIVE: To evaluate whether plasma levels of free fatty acids (FFAs) are
      independently associated with incidence of type 2 diabetes. RESEARCH DESIGN AND
      METHODS: A case-cohort design was used to randomly select 580 incident cases of
      diabetes and 566 noncases from 10,275 African-American and white men and women in
      the Atherosclerosis Risk in Communities study, aged 45-64 years and without
      prevalent diabetes at the baseline exam. Incident diabetes was ascertained at
      three exams over 9 years of follow-up. FFA levels were measured in plasma samples
      collected at the baseline exam. RESULTS: At baseline, FFA level was inversely
      associated with height and positively associated with female sex, BMI, waist
      circumference, waist-to-hip ratio, heart rate, plasma triglycerides, and an
      inflammation score quantifying levels of six systemic inflammation markers.
      Relative risks for incident diabetes (fourth vs. first quartile of FFAs) were
      increased in a basic model adjusted for age, sex, race, and center (hazard ratio
      1.68, 95% CI 1.20-2.34) and in a model further adjusted for baseline fasting
      glucose, insulin, BMI, waist circumference, triglycerides, and the inflammation
      score (1.63, 1.04-2.57). Relative risks associated with a greater FFA level were
      lowest among those of normal weight and highest among the obese, but a formal
      test of interaction between FFAs and BMI was not statistically significant.
      CONCLUSIONS: Individuals with higher fasting levels of plasma FFAs were at
      modestly higher risk of type 2 diabetes in this cohort of middle-aged adults.

PMID- 14693971
TI  - Exercise capacity and body composition as predictors of mortality among men with
      diabetes.
AB  - OBJECTIVE: To quantify the relation of fitness to mortality among men with
      diabetes, adjusted for BMI and within levels of BMI. RESEARCH DESIGN AND METHODS:
      In this observational cohort study, we calculated all-cause death rates in men
      with diabetes across quartiles of fitness and BMI categories. Study participants
      were 2,196 men with diabetes (average age 49.3 years, SD 9.5) who underwent a
      medical examination, including a maximal exercise test, during 1970 to 1995, with
      mortality follow-up to 31 December 1996. RESULTS: We identified 275 deaths during
      32,161 person-years of observation. Risk of all-cause mortality was inversely
      related to fitness. For example, in the fully adjusted model, the risk of
      mortality was 4.5 (2.6-7.6), 2.8 (1.6-4.7), and 1.6 (0.93-2.76) for the first,
      second, and third fitness quartiles, respectively, with the fourth quartile
      (highest fitness level) as the referent (P for trend <0.0001). There was no
      significant trend across BMI categories for mortality after adjustment for
      fitness. Similar results were found when the fitness-mortality relation was
      examined within levels of body composition. In normal-weight men with diabetes,
      the relative risks of mortality were 6.6 (2.8-15.0), 3.2 (1.4-7.0), and 2.2 (1.1
      4.6) for the first, second, and third quartiles of fitness, respectively, as
      compared with the fourth quartile (P for trend <0.0001). We found similar results
      in the overweight and obese weight categories. CONCLUSIONS: There was a steep
      inverse gradient between fitness and mortality in this cohort of men with
      documented diabetes, and this association was independent of BMI.

PMID- 14693972
TI  - A standardized triglyceride and carbohydrate challenge: the oral triglyceride
      tolerance test.
AB  - OBJECTIVE: A standardized method of assessing postprandial triglyceride changes
      is not available. We evaluated an oral triglyceride tolerance test (OTTT)
      designed for routine clinical and research use. RESEARCH DESIGN AND METHODS: A
      200-ml strawberry-flavored test drink (50 g fat, 50 g carbohydrate) was
      administered twice to 30 diabetic and 20 nondiabetic subjects. Venous plasma
      triglyceride and glucose levels were measured when fasting and every 2 h for 8 h
      after the drink. Fingerprick plasma triglyceride levels were measured when
      fasting and at 6 and 8 h after the drink. RESULTS: The drink was consumed within
      3 min and well tolerated by all subjects. The median triglyceride rise at 6 h was
      similar in diabetic and nondiabetic subjects (0.23 vs. 0.42 mmol/l, NS) and
      correlated with glucose increase at 2 h (r = 0.429, P = 0.018 and r = 0.509, P =
      0.026; respectively). Diabetic subjects had higher 6-h geometric mean (1 SD
      range) triglyceride levels (1.82 [1.87 to 3.23] vs. 1.11 [0.66 to 1.11 mmol/l], P
      < 0.003) but a similar coefficient of variation (17.5 vs. 17.0%, NS) and a
      similar median (interquartile range) time to achieve maximal concentration
      (T(max)) (6.0 [4.0 to 6.0] vs. 5.0 [4.0 to 6.0] h, NS). Capillary triglyceride
      values were equivalent to simultaneous venous samples but consistently 10%
      greater. CONCLUSIONS: The OTTT permits simple evaluation of postchallenge
      triglyceride levels, is acceptable to subjects, and can be performed with
      capillary sampling. It could be used to monitor triglyceride-lowering therapies
      and to provide additional information concerning cardiovascular disease risk,
      particularly in diabetic subjects.

PMID- 14693973
TI  - Closing the gap: effect of diabetes case management on glycemic control among low
      income ethnic minority populations: the California Medi-Cal type 2 diabetes
      study.
AB  - OBJECTIVE: Disparities exist in the diabetes health status of ethnic minority
      and/or low-income populations relative to other groups. A primary objective of
      diabetes management is to improve glycemic control. The feasibility of
      implementing intensive diabetes case management in disparate populations remains
      largely untested. RESEARCH DESIGN AND METHODS: Clinical sites in three southern
      California counties serving low-income, ethnic minority populations participated
      in our study. We randomized 362 Medicaid (called Medi-Cal in California)
      recipients with type 2 diabetes for at least 1 year to intervention (diabetes
      case management) or control (traditional primary care treatment) groups. Fifty
      five percent of participants were minorities. Participants with HbA(1c) levels
      less than 7.5%, serious diabetes-related complications, or other serious medical
      conditions were excluded. We assessed the effect of the intervention (ongoing
      diabetes case management added to primary care) on glycemic control using serial
      HbA(1c) measurements over several years. RESULTS: The mean duration of follow-up
      was 25.3 months. HbA(1c) decreased substantially in both groups from an average
      of 9.54-7.66% (a reduction of 1.88%) in the intervention group and from an
      average of 9.66-8.53% (a reduction of 1.13%) in the control group. This
      improvement was sustained throughout the study. The reduction in HbA(1c) was
      consistently greater in the intervention group at each time point (P < 0.001),
      ranging between 0.65 at 6 months and 0.87 at study end. CONCLUSIONS: Diabetes
      case management, added to primary care, substantially improved glycemic control
      compared with the control group. Diabetes case management can help reduce
      disparities in diabetes health status among low-income ethnic populations.

PMID- 14693974
TI  - Economic consequences of epidemiological changes in diabetes in middle-income
      countries: the Mexican case.
AB  - OBJECTIVE: To identify the costs and economic consequences of expected changes in
      the demand for health care services for type 2 diabetes in the three main public
      institutions of the Mexican health care system. RESEARCH DESIGN AND METHODS: The
      cost evaluation method to estimate direct and indirect costs was based on
      instrumentation and consensus techniques. To estimate the costs and
      epidemiological changes for 2003-2005, three probabilistic models were
      constructed according to the Box-Jenkins technique. RESULTS: Comparing the
      economic impact in 2003 versus 2005 (P < 0.05), there is a 26% increase in
      financial requirements. The total amount for diabetes in 2005 (in U.S. dollars)
      will be 317,631,206, dollars including 140,410,816 dollars in direct costs and
      177,220,390 dollars in indirect costs. The total direct costs, representing
      financial requirements to provide health care for expected cases of type 2
      diabetes and its main complications in the three main public institutions in
      Mexico, up to 2005, will be 37,079,587 dollars for the Ministry of Health (or
      Secretaria de Salud [SSA], serving the uninsured population) and 103,331,235
      dollars for the Mexican Social Security Institute, or Instituto Mexicano del
      Seguro Social (IMSS), and the Institute for Social Security and Services for
      State Workers, or Instituto de Seguridad y Servicios Sociales de los Trabajadores
      del Estado (ISSSTE), both of which serve the insured population. CONCLUSIONS: Our
      data suggest that changes in the demand for health care services for patients
      with diabetes will continue with an increasing trend, mainly in the insured
      population. In economic terms, the results of direct and indirect costs are one
      of the main challenges to be solved to decrease the economic burden that diabetes
      represents for the population, the health care institutions, and for society as a
      whole.

PMID- 14693975
TI  - Improvement in diabetes care of underinsured patients enrolled in project dulce:
      a community-based, culturally appropriate, nurse case management and peer
      education diabetes care model.
AB  - OBJECTIVE: To improve clinical diabetes care, patient knowledge, and treatment
      satisfaction and to reduce health-adverse culture-based beliefs in underserved
      and underinsured populations with diabetes. RESEARCH DESIGN AND METHODS: A total
      of 153 high-risk patients with diabetes recruited from six community clinic sites
      in San Diego County, California were enrolled in a nurse case management (NCM)
      and peer education/empowerment group. Baseline and 1-year levels of HbA(1c),
      lipid parameters, systolic and diastolic blood pressure, knowledge of diabetes,
      culture-based beliefs in ineffective remedies, and treatment satisfaction were
      prospectively measured. The NCM and peer education/empowerment group was compared
      with 76 individuals in a matched control group (CG) derived from patients
      referred but not enrolled in Project Dulce. RESULTS: After 1 year in Project
      Dulce, the NCM and peer education/empowerment group had significant improvements
      in HbA(1c) (12.0-8.3%, P < 0.0001), total cholesterol (5.82-4.86 mmol/l, P <
      0.0001), LDL cholesterol (3.39-2.79 mmol/l, P < 0.0001), and diastolic blood
      pressure (80-76 mmHg, P < 0.009), which were significantly better than in the CG,
      in which no significant changes were noted. Accepted American Diabetes
      Association standards of diabetes care, knowledge of diabetes (P = 0.024),
      treatment satisfaction (P = 0.001), and culture-based beliefs (P = 0.001) were
      also improved. CONCLUSIONS: A novel, culturally appropriate, community-based,
      nurse case management/peer education diabetes care model leads to significant
      improvement in clinical diabetes care, self-awareness, and understanding of
      diabetes in underinsured populations.

PMID- 14693976
TI  - The performance of a risk score as a screening test for undiagnosed hyperglycemia
      in ethnic minority groups: data from the 1999 health survey for England.
AB  - OBJECTIVE: To assess the performance of the Cambridge Risk Score (CRS) to predict
      undiagnosed hyperglycemia in Caribbean and South Asian people living in the U.K.
      RESEARCH DESIGN AND METHODS: The CRS uses routinely available data from primary
      care records to identify people at high risk for undiagnosed type 2 diabetes. The
      sensitivity, specificity, and area under the receiver operator characteristic
      (ROC) curve for the CRS cut point of 0.199 were 77, 72, and 80% (95% CI 68-91),
      respectively. The risk score was calculated for 248 Caribbean and 555 South Asian
      participants aged 40-75 years in the 1999 Health Survey for England. Undiagnosed
      hyperglycemia was considered present if fasting plasma glucose was >/=7.0 mmol/l
      or HbA(1c) was >/=6.5%. Sensitivity, specificity, and predictive values were
      calculated for various cut points of the risk score, and ROC curves were
      constructed. RESULTS: The area under the ROC curve was 67% (59-76) and 72% (67
      78) for Caribbeans and South Asians, respectively. The optimal cut point in
      Caribbean participants was 0.236, sensitivity was 63% (46-77), and specificity
      was 63% (56-69). In the South Asian population, the optimal cut point was and
      0.127, sensitivity was 69% (60-78), and specificity was 64% (60-69). CONCLUSIONS:
      The CRS, using routinely available data, can be used in a strategy to detect
      undiagnosed hyperglycemia in Caribbean and South Asian populations. The existence
      of ethnic group-specific cut points must be further established in future
      studies.

PMID- 14693977
TI  - Physician, organizational, and patient factors associated with suboptimal blood
      pressure management in type 2 diabetic patients in primary care.
AB  - OBJECTIVE: To assess the quality of hypertension care in patients with type 2
      diabetes in general practice and identify physician, organizational, and patient
      factors associated with suboptimal care. RESEARCH DESIGN AND METHODS: Data from
      895 randomly selected diabetic patients were extracted from the electronic
      medical records of 95 general practitioners. Physician and organizational
      characteristics were collected with a questionnaire. We conducted a multilevel
      analysis to identify associations with blood pressure registration, hypertension
      treatment, and achievement of target blood pressure levels. RESULTS: For 652
      patients (73%), a blood pressure measurement was recorded in the last year. Of
      these patients, 132 (20%) reached a target level of 135/85 mmHg. In total, 595
      patients were classified as having hypertension, of whom 192 received no
      treatment (32%), 193 received an ACE inhibitor (32%), and 210 received other
      antihypertensives. Patients visiting a diabetes facility, referred to a
      specialist, with a female general practitioner, or with a general practitioner
      with </=10 years work experience had better recordings of their blood pressure.
      Suboptimal treatment was higher in older patients and smoking patients. Treatment
      was better in patients with coronary comorbidity, hyperlipidemia, or those
      referred to a specialist. Not achieving the blood pressure target was related to
      older age of the patients. CONCLUSIONS: Hypertension management of type 2
      diabetic patients in primary care is suboptimal. Characteristics of general
      practitioners as well as additional care provided by a diabetes facility or a
      specialist are associated with better processes of care, but blood pressure
      outcomes are not as clearly related to these factors.

PMID- 14693978
TI  - Depressive symptoms and risk of type 2 diabetes in women.
AB  - OBJECTIVE: To explore the relationship between depressive symptoms and incidence
      of type 2 diabetes in women. RESEARCH DESIGN AND METHODS: We conducted an
      analysis of 72,178 female nurses aged 45-72 years who did not have diagnosed
      diabetes and who answered the Medical Outcomes Study 36-Item Short-Form Health
      Status Survey (SF-36) at baseline in 1992. We calculated relative risks (RR) of
      type 2 diabetes for women with presence of depressive symptoms (i.e., Five-Item
      Mental Health Index [MHI-5] score >52). RESULTS: During 4 years of follow-up
      (282,317 person-years), 973 incident cases of type 2 diabetes were documented.
      Age-adjusted RR of developing type 2 diabetes for women with presence of
      depressive symptoms was 1.55 (95% CI 1.27-1.90). Additional adjustment for BMI
      resulted in a RR of developing type 2 diabetes of 1.36 (1.11-1.67). The
      multivariate RR of developing type 2 diabetes was 1.22 (1.00-1.50). After
      excluding women diagnosed with diabetes between 1992 and 1994, 472 incident cases
      of type 2 diabetes were documented for the follow-up period from 1994 to 1996
      (148,889 person-years). The multivariate RR of developing type 2 diabetes for
      women with depressive symptoms was 1.29 (0.96-1.72). CONCLUSIONS: Our data
      suggest that depressive symptoms are associated with a modest increase in the
      risk of type 2 diabetes.

PMID- 14693979
TI  - Magnesium intake and risk of type 2 diabetes in men and women.
AB  - OBJECTIVE: To examine the association between magnesium intake and risk of type 2
      diabetes. RESEARCH DESIGN AND METHODS: We followed 85,060 women and 42,872 men
      who had no history of diabetes, cardiovascular disease, or cancer at baseline.
      Magnesium intake was evaluated using a validated food frequency questionnaire
      every 2-4 years. After 18 years of follow-up in women and 12 years in men, we
      documented 4,085 and 1,333 incident cases of type 2 diabetes, respectively.
      RESULTS: After adjusting for age, BMI, physical activity, family history of
      diabetes, smoking, alcohol consumption, and history of hypertension and
      hypercholesterolemia at baseline, the relative risk (RR) of type 2 diabetes was
      0.66 (95% CI 0.60-0.73; P for trend <0.001) in women and 0.67 (0.56-0.80; P for
      trend <0.001) in men, comparing the highest with the lowest quintile of total
      magnesium intake. The RRs remained significant after additional adjustment for
      dietary variables, including glycemic load, polyunsaturated fat, trans fat,
      cereal fiber, and processed meat in the multivariate models. The inverse
      association persisted in subgroup analyses according to BMI, physical activity,
      and family history of diabetes. CONCLUSIONS: Our findings suggest a significant
      inverse association between magnesium intake and diabetes risk. This study
      supports the dietary recommendation to increase consumption of major food sources
      of magnesium, such as whole grains, nuts, and green leafy vegetables.

PMID- 14693980
TI  - One-year glycemic control with a sulfonylurea plus pioglitazone versus a
      sulfonylurea plus metformin in patients with type 2 diabetes.
AB  - OBJECTIVE: The goal was to assess the 1-year efficacy and safety of the addition
      of pioglitazone or metformin to existing sulfonylurea (SU) therapy in patients
      with inadequately controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: In
      this multicenter, double-blind study, patients were randomized to receive either
      pioglitazone 15 mg (n = 319) or metformin 850 mg (n = 320) and up to 45 mg/day
      and 2,550 mg/day, respectively. The primary efficacy endpoint was HbA(1c) at week
      52. Fasting plasma glucose, insulin, and lipid profiles were also measured.
      RESULTS: HbA(1c) was reduced by 1.20% in the SU plus pioglitazone group and 1.36%
      in the SU plus metformin group, and fasting plasma glucose was reduced by 2.2 and
      2.3 mmol/l in the respective groups. Fasting insulin levels were also reduced
      (pioglitazone arm -1.3 micro IU/ml; metformin arm -0.8 micro IU/ml). There were
      no significant between-treatment differences in these three parameters.
      Pioglitazone addition to SU significantly reduced triglycerides (-16 vs. -9%; P =
      0.008) and increased HDL cholesterol (14 vs. 8%; P < 0.001) compared with
      metformin addition. LDL cholesterol was increased 2% by the addition of
      pioglitazone and decreased 5% by the addition of metformin to SU (P < 0.001).
      Urinary albumin-to-creatinine ratio was reduced by 15% in the SU plus
      pioglitazone group and increased 2% in the SU plus metformin group (P = 0.017).
      Both combinations were well tolerated with no evidence of hepatic or cardiac
      toxicity in either group. CONCLUSIONS: Clinically equivalent improvements in
      glycemic control were observed for both combinations. Compared with metformin
      plus SU, addition of pioglitazone to SU resulted in a reduction of the urinary
      albumin-to-creatinine ratio, a small but significant rise in LDL cholesterol, and
      significantly greater improvements in triglyceride levels and HDL cholesterol
      levels. Metformin plus SU was associated with a significant reduction in LDL
      cholesterol. SU plus pioglitazone is an effective and well-tolerated combination
      regimen that may provide additional beneficial effects for patients with type 2
      diabetes.

PMID- 14693981
TI  - Effects of troglitazone in young first-degree relatives of patients with type 2
      diabetes.
AB  - OBJECTIVE: Insulin resistance is a key characteristic of first-degree relatives
      of patients with type 2 diabetes. We therefore treated young, glucose-tolerant
      relatives with the insulin action enhancer troglitazone in order to determine the
      effects on insulin sensitivity, glucose metabolism, and glycogen synthase
      activity. RESEARCH DESIGN AND METHODS: Relatives were randomized in a double
      blind manner and treated for 12 weeks with either 200 mg troglitazone or placebo.
      Before and after treatment, an oral glucose tolerance test (OGTT) and a
      euglycemic-hyperinsulinemic clamp (40 mU. m(-2). min(-1)) were performed,
      including 3-(3)H glucose infusion, glycolytic flux calculations, indirect
      calorimetry, and muscle biopsies. RESULTS: Twelve relatives received troglitazone
      and 12 placebo (aged 30.8 +/- 2.0 vs. 30.3 +/- 1.6 years, BMI 29.6 +/- 0.8 vs.
      30.5 +/- 1.3 kg/m(2); means +/- SE). Area under the curve (AUC) for plasma
      glucose at the second OGTT was unchanged after troglitazone. In contrast,
      troglitazone reduced fasting (from 70.3 +/- 6.9 to 52.2 +/- 5.8 vs. 73.6 +/- 11.0
      to 73.3 +/- 6.5 pmol/l, P < 0.02) and AUC plasma insulin (mean [CI] from 335.7
      [230.9-488.1] to 277.4 [179.4-428.8] vs. 313.8 [218.2-451.2] to 353.9 [208.3
      601.3] pmol/l, P < 0.05). Additionally, fasting plasma triglycerides were reduced
      by troglitazone (from 1.86 +/- 0.33 to 1.38 +/- 0.27 vs. 2.22 +/- 0.44 to 2.35 +/
      0.46 mmol/l, P < 0.01). Insulin-stimulated glucose disposal increased in the
      troglitazone group (from 208.3 +/- 23.7 to 263.5 +/- 30.4 vs. 197.1 +/- 20.0 to
      200.8 +/- 20.8 mg. m(-2). min(-1), P < 0.02) mainly due to increased glucose
      storage (from 99.9 +/- 17.9 to 146.0 +/- 25.3 vs. 87.1 +/- 16.7 to 87.9 +/- 15.7
      mg. m(-2). min(-1), P < 0.02), which took place without altering insulin
      stimulated glycogen synthase activity. CONCLUSIONS: In glucose-tolerant first
      degree relatives, treatment with troglitazone improved insulin sensitivity almost
      50%, primarily due to increased glucose storage. It is suggested that the use of
      insulin action enhancers can be especially valuable in this group of subjects
      with a known high risk for developing type 2 diabetes.

PMID- 14693982
TI  - XENical in the prevention of diabetes in obese subjects (XENDOS) study: a
      randomized study of orlistat as an adjunct to lifestyle changes for the
      prevention of type 2 diabetes in obese patients.
AB  - OBJECTIVE: It is well established that the risk of developing type 2 diabetes is
      closely linked to the presence and duration of overweight and obesity. A
      reduction in the incidence of type 2 diabetes with lifestyle changes has
      previously been demonstrated. We hypothesized that adding a weight-reducing agent
      to lifestyle changes may lead to an even greater decrease in body weight, and
      thus the incidence of type 2 diabetes, in obese patients. RESEARCH DESIGN AND
      METHODS: In a 4-year, double-blind, prospective study, we randomized 3,305
      patients to lifestyle changes plus either orlistat 120 mg or placebo, three times
      daily. Participants had a BMI >/=30 kg/m2 and normal (79%) or impaired (21%)
      glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes
      and change in body weight. Analyses were by intention to treat. RESULTS: Of
      orlistat-treated patients, 52% completed treatment compared with 34% of placebo
      recipients (P < 0.0001). After 4 years' treatment, the cumulative incidence of
      diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk
      reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the
      preventive effect was explained by the difference in subjects with IGT. Mean
      weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg
      with placebo; P < 0.001) and similar between orlistat recipients with impaired
      (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second
      analysis in which the baseline weights of subjects who dropped out of the study
      was carried forward also demonstrated greater weight loss in the orlistat group
      (3.6 vs. 1.4 kg; P < 0.001). CONCLUSIONS: Compared with lifestyle changes alone,
      orlistat plus lifestyle changes resulted in a greater reduction in the incidence
      of type 2 diabetes over 4 years and produced greater weight loss in a clinically
      representative obese population. Difference in diabetes incidence was detectable
      only in the IGT subgroup; weight loss was similar in subjects with IGT or NGT
      [correction].

PMID- 14693983
TI  - Intensive therapy with inhaled insulin via the AERx insulin diabetes management
      system: a 12-week proof-of-concept trial in patients with type 2 diabetes.
AB  - OBJECTIVE: To compare the glycemic control of inhaled insulin via the AERx
      insulin diabetes management system (iDMS) with that of subcutaneous (SC) insulin,
      both combined with NPH insulin at bedtime, in patients with type 2 diabetes.
      RESEARCH DESIGN AND METHODS: The AERx iDMS uses a liquid insulin formulation to
      achieve flexible precise mealtime dosing (with increments corresponding to 1 IU
      administered subcutaneously) and ensures insulin delivery only when the breathing
      technique is optimal. This trial in patients with type 2 diabetes compared the
      glycemic control (HbA(1c)) achieved by inhaled insulin administered via AERx iDMS
      with that using SC insulin. This was a randomized, 12-week, open-label, parallel,
      multicenter, multinational trial in 107 nonsmoking patients with type 2 diabetes
      (mean age 59 years, mean duration of diabetes 11.9 years). Patients were
      randomized to receive either inhaled fast-acting human insulin via AERx iDMS
      immediately before meals or SC fast-acting human insulin administered 30 min
      before meals, both in combination with evening NPH insulin. RESULTS: Baseline and
      demographic characteristics were similar between the two groups. There was no
      statistically significant difference in HbA(1c) between the AERx and SC groups
      after 12 weeks of treatment (7.84 +/- 0.77 vs. 7.76 +/- 0.77%, P = 0.60). Fasting
      serum glucose was significantly lower in the AERx group compared with the SC
      group by the end of the trial (8.9 +/- 3.8 vs. 10.8 +/- 3.7 mmol/l, P = 0.01)
      with a similar NPH dose in the two groups (0.23 vs. 0.23 IU/kg, P = 0.93). There
      were no statistically significant differences between the two groups in the intra
      subject variability of fasting or prandial blood glucose increment. Adverse
      events were similar in the two groups. No major safety concerns were raised
      during the trial. CONCLUSIONS: In patients with type 2 diabetes, preprandial
      inhaled insulin via AERx iDMS is as effective as preprandial SC insulin injection
      in achieving glycemic control with similar tolerability.

PMID- 14693984
TI  - Restoration of sensation, reduced pain, and improved balance in subjects with
      diabetic peripheral neuropathy: a double-blind, randomized, placebo-controlled
      study with monochromatic near-infrared treatment.
AB  - OBJECTIVE: Diabetic peripheral neuropathy (DPN) has been thought to be
      progressive and irreversible. Recently, symptomatic reversal of DPN was reported
      after treatments with a near-infrared medical device, the Anodyne Therapy System
      (ATS). However, the study was not controlled nor was the investigator blinded. We
      initiated this study to determine whether treatments with the ATS would decrease
      pain and/or improve sensation diminished due to DPN under a sham-controlled,
      double-blind protocol. RESEARCH DESIGN AND METHODS: Tests involved the use of the
      5.07 and 6.65 Semmes Weinstein monofilament (SWM) and a modified Michigan
      Neuropathy Screening Instrument (MNSI). Twenty-seven patients, nine of whom were
      insensitive to the 6.65 SWM and 18 who were sensitive to this filament but
      insensitive to the 5.07 SWM, were studied. Each lower extremity was treated for 2
      weeks with sham or active ATS, and then both received active treatments for an
      additional 2 weeks. RESULTS: The group of 18 patients who could sense the 6.65
      SWM but were insensitive to the 5.07 SWM at baseline obtained a significant
      decrease in the number of sites insensate after both 6 and 12 active treatments
      (P < 0.02 and 0.001). Sham treatments did not improve sensitivity to the SWM, but
      subsequent active treatments did (P < 0.002). The MNSI measures of neuropathic
      symptoms decreased significantly (from 4.7 to 3.1; P < 0.001). Pain reported on
      the 10-point visual analog scale decreased progressively from 4.2 at entry to 3.2
      after 6 treatments and to 2.3 after 12 treatments (both P < 0.03). At entry, 90%
      of subjects reported substantial balance impairment; after treatment, this
      decreased to 17%. However, among the group of nine patients with greater sensory
      impairment measured by insensitivity to the 6.65 SWM at baseline, improvements in
      sensation, neuropathic symptoms, and pain reduction were not significant.
      CONCLUSIONS: ATS treatments improve sensation in the feet of subjects with DPN,
      improve balance, and reduce pain.

PMID- 14693985
TI  - Postural control mechanisms during quiet standing in patients with diabetic
      sensory neuropathy.
AB  - OBJECTIVE: The objective of the present study was to compare postural mechanisms
      identified by using dual force platform in healthy elderly community-dwelling
      subjects and diabetic sensory neuropathy (DSN) patients under different visual
      conditions. RESEARCH DESIGN AND METHODS: The presence and the severity of the
      sensory neuropathy was evaluated with a clinical scale. Postural mechanisms and
      motor strategies of the ankle and hip joints were quantified by testing subjects
      in quiet stance on a dual force platform under two visual conditions (eyes open
      and eyes closed). Root mean square (RMS) values of the center of pressure (COP)
      time-varying signals and normalized cross-correlation function were used to
      estimate the contribution and the interdependence of postural control mechanisms.
      RESULTS: DSN patients show larger RMS values of the COP(net) displacement in both
      anteroposterior and mediolateral (ML) directions. Motor strategies at the ankle
      joints are altered in DSN patients compared with healthy elderly subjects
      particularly in the ML direction. CONCLUSIONS: This experiment is the first to
      highlight that even with vision, postural mechanisms at the ankle joints are
      impaired in DSN patients during quiet standing. Our results point out the
      importance of focusing on postural control instability in ML of DSN patients.

PMID- 14693986
TI  - Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with a reduced
      prevalence of diabetic neuropathy in patients with type 2 diabetes.
AB  - OBJECTIVE: To establish whether single nucleotide polymorphisms (Asp299Gly and
      Thr399Ile) of the toll-like receptor 4 have an association with late diabetic
      complications. RESEARCH DESIGN AND METHODS: The study was conducted in 246 type 1
      and 530 type 2 diabetic patients. The alleles of both polymorphisms were detected
      using PCR and subsequent cleavage by NcoI and HinfI restriction endonucleases.
      RESULTS: No difference was found between type 1 and type 2 diabetic patients in
      the prevalence of alleles of the Asp299Gly and Thr399Ile polymorphisms. In most
      cases, the alleles Gly299 and Ile399 occurred in a co-segregatory manner. The
      prevalence of the Gly299/Ile399 haplotype was 10.6 and 12.1% in type 1 and type 2
      diabetic patients, respectively (P = 0.63). No association with diabetic
      nephropathy or diabetic neuropathy was found in type 1 diabetic patients. In type
      2 diabetic patients, however, heterozygote carriers of the Asp299Gly and
      Thr399Ile genotypes had a significantly reduced prevalence of diabetic neuropathy
      (odds ratio 0.35 [95% CI 0.19-0.61]; P = 0.0002); no association with diabetic
      nephropathy was found. CONCLUSIONS: Our data indicate that Asp299Gly and
      Thr399Ile genotypes of the TLR4 gene are associated with reduced prevalence of
      diabetic neuropathy in type 2, but not in type 1, diabetes. Thus different
      mechanisms may be involved in the pathophysiology of diabetic neuropathy in type
      1 and type 2 diabetes.

PMID- 14693987
TI  - Effect of moderate alcohol consumption on adiponectin, tumor necrosis factor
      alpha, and insulin sensitivity.
AB  - OBJECTIVE: Epidemiological studies suggest that moderate alcohol consumers have
      enhanced insulin sensitivity and a reduced risk of type 2 diabetes. Adiponectin,
      an adipocyte-derived plasma protein, has been found to be negatively associated
      with adiposity and positively associated with insulin sensitivity. Moderate
      alcohol consumption may increase adiponectin, which in turn causes a decrease of
      tumor necrosis factor (TNF)-alpha. A decreased TNF-alpha level may consequently
      increase insulin sensitivity. RESEARCH DESIGN AND METHODS: To test this
      hypothesis, we performed a randomized crossover partially diet-controlled study.
      A total of 23 healthy middle-aged male subjects consumed daily four glasses of
      whisky (40 g ethanol) or tap water with dinner during two successive periods of
      17 days. RESULTS: Moderate alcohol consumption increased plasma adiponectin level
      (11%; P = 0.0002) but did not affect plasma TNF-alpha level. An increase in
      insulin sensitivity index was observed in an insulin-resistant subgroup (21%; P =
      0.11), which positively correlated with the relative alcohol-induced increase in
      plasma adiponectin level (r = 0.73, P = 0.02). CONCLUSIONS: The experimental
      results are in agreement with observational data. Moderate alcohol consumption
      improved insulin sensitivity in relatively insulin-resistant middle-aged men, an
      effect that may be mediated through alcohol-induced increases in adiponectin.

PMID- 14693988
TI  - Acanthocytes in the urine: useful tool to differentiate diabetic nephropathy from
      glomerulonephritis?
AB  - OBJECTIVE: The presence of hematuria has been suggested to indicate nondiabetic
      nephropathy in diabetic patients with proteinuria. However, hematuria is
      frequently found in patients with biopsy-proven diabetic glomerulosclerosis
      without nondiabetic nephropathy. Urine microscopy allows discrimination of
      glomerular hematuria, which is defined as acanthocyturia (urinary excretion of
      acanthocytes, which are dysmorphic erythrocytes with vesicle-like protrusions),
      from nonglomerular hematuria. We hypothesized that acanthocyturia is an uncommon
      finding in diabetic nephropathy, which suggests the presence of a nondiabetic
      nephropathy in diabetic patients with proteinuria. RESEARCH DESIGN AND METHODS:
      Urine samples of patients with the clinical diagnosis of diabetic nephropathy (n
      = 68), of patients with biopsy-proven glomerulonephritis (n = 43), and of age
      matched healthy control subjects (n = 20) were examined by phase-contrast
      microscopy for the presence of hematuria (>/=8 erythrocytes/ micro l) and
      acanthocyturia. Acanthocyturia of >/=5% (5 acanthocytes among 100 excreted
      erythrocytes) was classified as glomerular hematuria; acanthocyturia of 2-4% was
      classified as suspected glomerular hematuria. RESULTS: Hematuria was found in 62%
      of patients with the clinical diagnosis of diabetic nephropathy, in 84% of
      patients with glomerulonephritis, and in 20% of the healthy control subjects upon
      a single urine examination. In contrast, glomerular hematuria occurred in 4% of
      patients with diabetic nephropathy and in 40% of patients with glomerulonephritis
      (P < 0.001). CONCLUSIONS: In contrast to hematuria, acanthocyturia is uncommon in
      patients with the clinical diagnosis of diabetic nephropathy. In diabetic
      patients with proteinuria, the finding of acanthocyturia points to nondiabetic
      glomerulopathies, and renal biopsy should be considered.

PMID- 14693989
TI  - Nonalbuminuric renal insufficiency in type 2 diabetes.
AB  - OBJECTIVE: To determine the prevalence and characteristics of patients with type
      2 diabetes who have impaired renal function, defined as a glomerular filtration
      rate (GFR) <60 ml. min(-1). 1.73 m(-2), and normoalbuminuria. RESEARCH DESIGN AND
      METHODS: A cross-sectional survey of 301 outpatients attending a single tertiary
      referral center using the plasma disappearance of isotopic (99m)Tc-diethylene
      triamine-penta-acetic acid to measure GFR and at least two measurements of
      urinary albumin excretion rate (AER) over 24 h to determine albuminuria. RESULTS:
      A total of 109 patients (36%) had a GFR <60 ml. min(-1). 1.73 m(-2). The overall
      prevalence of normo-, micro-, and macroalbuminuria was 43 of 109 (39%), 38 of 109
      (35%), and 28 of 109 (26%), respectively. Compared with patients with
      macroalbuminuria, those with normoalbuminuria were more likely to be older and
      female. After excluding patients whose normoalbuminuric status was possibly
      related to the initiation of a renin-angiotensin system (RAS) inhibitor before
      the start of the study, the prevalence of a GFR <60 ml. min(-1). 1.73 m(-2) and
      normoalbuminuria was 23%. Temporal changes in GFR in a subset of 34 of 109 (32%)
      unselected patients with impaired renal function were available for comparison
      over a 3- to 10-year period. The rates of decline in GFR (ml. min(-1). 1.73 m(
      2). year(-1)) of -4.6 +/- 1.0, -2.8 +/- 1.0, and -3.0 +/- 07 were not
      significantly different for normo- (n = 12), micro- (n = 12), and
      macroalbuminuric (n = 10) patients, respectively. CONCLUSIONS: These results
      suggest that patients with type 2 diabetes can commonly progress to a significant
      degree of renal impairment while remaining normoalbuminuric.

PMID- 14693990
TI  - Risk factors for myocardial infarction case fatality and stroke case fatality in
      type 2 diabetes: UKPDS 66.
AB  - OBJECTIVE: Patients with diabetes have a higher case fatality rate in myocardial
      infarction (MI) or stroke than those without diabetes: that is, MI and stroke are
      more often fatal if diabetes is present. We investigated whether the risk of MI
      or stroke being fatal in type 2 diabetes can be estimated using information
      available around the time diabetes is diagnosed. RESEARCH DESIGN AND METHODS:
      Analyses were based on 674 cases of MI (351 fatal) that occurred in 597 of 5,102
      U.K. Prospective Diabetes Study (UKPDS) patients for whom covariate data were
      available during a median follow-up of 7 years. Multivariate logistic regression
      was used to examine differences in risk factors, measured within 2 years of
      diagnosis of diabetes, between fatal and nonfatal MI. Similar analyses were
      performed for 234 strokes (48 fatal) that occurred in 199 patients. RESULTS:
      Patients with fatal MI had higher HbA(1c) than those with nonfatal MI (odds ratio
      1.17 per 1% HbA(1c), P = 0.014). Patients with fatal stroke had higher HbA(1c)
      than those with nonfatal stroke (odds ratio 1.37 per 1% HbA(1c), P = 0.007).
      Other risk factors for MI case fatality included increased age, blood pressure,
      and urine albumin level. CONCLUSIONS: The risk of MI or stroke being fatal in
      type 2 diabetes is associated with risk factors, including HbA(1c), measured many
      years before onset of MI or stroke. Equations have been added to the UKPDS Risk
      Engine to estimate likely case fatality rates in MI and stroke.

PMID- 14693991
TI  - Prognostic value of epicardial coronary artery constriction to the cold pressor
      test in type 2 diabetic patients with angiographically normal coronary arteries
      and no other major coronary risk factors.
AB  - OBJECTIVE: Endothelium-dependent coronary dilation is impaired in diabetic
      patients and has been found to independently predict cardiovascular events (CVEs)
      in patients with multiple coronary risk factors. The aim of this study was to
      evaluate the outcome of type 2 diabetic patients on the basis of epicardial
      coronary dysfunction. RESEARCH DESIGN AND METHODS: We examined 56 control
      subjects (aged 51.7 +/- 6.4 years) using coronary artery response to the cold
      pressor test (quantitative coronary angiography) and compared them with 72 type 2
      diabetic patients (aged 50.3 +/- 8.5 years) without other major coronary risk
      factors. RESULTS: Average diameter change was 17.2 +/- 10.4% in the control
      subjects, dilation occurred in 91.1% of subjects, no change occurred in 8.9%, and
      there was no constriction. Average diameter change was -14.4 +/- 12.1% in
      diabetic patients (P < 0.001 vs. control subjects), constriction occurred in
      73.6%, no change occurred in 26.4%, and there was no dilation. CVEs were recorded
      with a mean follow-up of 45 +/- 19 months. There was 1 CVE in the control group
      and 26 CVEs in 18 of 72 diabetic patients (P < 0.001 vs. control subjects), with
      23 events in 16 of 53 diabetic patients with coronary artery constriction (P <
      0.001 vs. control subjects), and 3 events in 2 of 19 diabetic patients with no
      diameter change (NS vs. control subjects). CONCLUSIONS: In type 2 diabetic
      patients without other major coronary risk factors, constriction of
      angiographically normal coronary arteries to the cold pressor test is predictive
      of long-term CVEs.

PMID- 14693992
TI  - White blood cell count is associated with macro- and microvascular complications
      in chinese patients with type 2 diabetes.
AB  - OBJECTIVES: There are close associations among raised white blood cell (WBC)
      count, coronary heart disease, and metabolic syndrome in the general population.
      The association between WBC count and vascular complications of diabetes has not
      been explored. We carried out a cross-sectional cohort study to determine the
      association between WBC count and the presence of macro- and microvascular
      complications in type 2 diabetes. RESEARCH DESIGN AND METHODS: In this study,
      3,776 patients with type 2 diabetes and normal WBC count (3.5-12.5 x 10(9)/l)
      underwent a comprehensive assessment of complications and cardiovascular risk
      factors based on the European DiabCare protocol. Demographic and anthropometric
      parameters were recorded. Metabolic profiles, including complete blood picture
      and urinary albumin excretion, were measured. RESULTS: Patients with higher WBC
      counts (categorized into quintiles) had adverse metabolic profiles as evidenced
      by higher blood pressure, BMI, HbA(1c), fasting plasma glucose, LDL cholesterol,
      triglycerides, and urinary albumin excretion, but lower HDL cholesterol (all P
      <0.001 for trend). The prevalence of macro- and microvascular complications
      increased in a dosage-related manner with WBC count. After adjustments for
      smoking and other known cardiovascular risk factors, a 1-unit (1 x 10(9)/l)
      increment of WBC count was associated with a 15.8% (95% CI 9.3-22.6; P < 0.001)
      and 12.3% increase (5.8-19.1; P < 0.001) in the prevalence of macro- and
      microvascular complications, respectively. CONCLUSIONS: Elevated WBC count, even
      within the normal range, is associated with both macro- and microvascular
      complications in type 2 diabetes. Chronic inflammation, as indicated by a higher
      WBC count, may play a linkage role in the development of macro- and microvascular
      complications in diabetes.

PMID- 14693993
TI  - Association between acute-phase reactants and advanced glycation end products in
      type 2 diabetes.
AB  - OBJECTIVE: Type 2 diabetes is associated with chronic low-grade inflammation, but
      the underlying mechanism(s) is not well understood. Because in vitro studies have
      shown that advanced glycation end products (AGEs) can trigger inflammatory
      responses, the present study has investigated whether serum concentration of AGEs
      is an important determinant of circulating levels of inflammatory markers, like C
      reactive protein (CRP), in type 2 diabetic patients. RESEARCH DESIGN AND METHODS:
      Diabetic patients (n = 210) and healthy control subjects (n = 110) of similar BMI
      were recruited. Serum AGEs were assayed by competitive enzyme-linked
      immunosorbent assay using a polyclonal rabbit anti-sera raised against AGE-RNase.
      Plasma high-sensitivity CRP was measured by an immunoturbidimetric assay and
      interleukin (IL)-6 by enzyme-linked immunosorbent assay. RESULTS: Serum AGEs were
      increased in diabetic patients compared with control subjects (4.24 +/- 0.88 vs.
      3.15 +/- 0.81 unit/ml, respectively, P < 0.01). Both plasma CRP (1.55 [0.81-2.95]
      vs. 0.88 mg/dl [0.51-1.89], respectively, P < 0.01; median [interquartile range])
      and IL-6 (0.80 [0.68-0.97] vs. 0.69 pg/ml [0.48-0.84], respectively, P < 0.01)
      were also higher in diabetic patients than in control subjects. In the diabetic
      patients, log(CRP) correlated with AGEs (r = 0.22, P = 0.002) and with log(IL-6)
      (r = 0.29, P < 0.001). Forward stepwise linear regression analysis showed that
      BMI, log(IL-6), and AGEs were significant independent determinants of log(CRP) in
      the diabetic patients, accounting for 17, 12, and 10% of the variation in
      log(CRP), respectively. CONCLUSIONS: Serum concentration of AGEs is increased in
      patients with diabetes and is an independent determinant of plasma CRP levels.
      Subclinical inflammation in these patients may therefore be partly due to
      activation of the inflammatory response by AGEs.

PMID- 14693994
TI  - Infections in diabetic burn patients.
AB  - OBJECTIVE: Diabetic burn patients comprise a significant population in burn
      centers. The purpose of the study was to determine the demographic
      characteristics of diabetic burn patients and their rate of community-acquired
      and nosocomial infections. RESEARCH DESIGN AND METHODS: This was a 46-month
      retrospective chart and patient registry review comparing diabetic with
      nondiabetic burn patients. Statistical analysis consisted of means +/- SD,
      descriptive statistics, one-way ANOVA, and chi(2) tests. RESULTS: Of 1,063 adult
      burn patients (aged 15-54 years), 68 (6%) diabetic burns were compared with burns
      of 995 adult nondiabetic patients. Of 193, 62 (32%) senior (>/=55 years of age)
      diabetic burns were compared with 131 nondiabetic senior burns. The major
      mechanism of injury for the diabetic patients was scalding and contact, in
      contrast to that of nondiabetic patients who were injured mainly by scalding or
      flame burns. Adult diabetic patients had a significantly increased frequency of
      foot burns compared with adult nondiabetic patients (32 of 68 [68%] versus 144 of
      995 [14%], P = 0.001). Adult diabetic burns had a significant increase in sepsis
      (P < 0.002) and community-acquired burn wound cellulitis (P < 0.001) compared
      with adult nondiabetic patients; and senior diabetic patients had a significantly
      increased frequency of urinary tract infections compared with senior nondiabetic
      burn patients (P < 0.04). The most common organisms in diabetic burn infections
      were Streptococcus, Proteus, Pseudomonas, Candida species, and MRSA (methicillin
      resistant Staphylococcus aureus). Forty-two percent of the diabetic patients were
      admitted during the winter months and 25% in the spring. Only 49 of 130 (38%)
      diabetic burn patients presented for treatment within 48 h after injury compared
      with 669 of 1,126 (62%) nondiabetic patients (P = 0.001). CONCLUSIONS: Peripheral
      neuropathy may have precipitated and delayed medical treatment in lower-extremity
      burns of diabetic patients. Hospitalized diabetic burn patients were also at an
      increased risk for nosocomial infections, which prolonged hospitalization.
      Diabetic patient education must include not only caution about potential burn
      mishaps but also educate concerning the complications from burns that may ensue.

PMID- 14693995
TI  - The prevalence of the metabolic syndrome among arab americans.
AB  - OBJECTIVE: To estimate the prevalence of the metabolic syndrome in Arab Americans
      by age, sex, and BMI and to examine the association between insulin resistance
      and each of the components of the metabolic syndrome. RESEARCH DESIGN AND
      METHODS: We studied a representative, cross-sectional, population-based sample of
      542 Arab Americans aged 20-75 years. The metabolic syndrome was defined by Adult
      Treatment Panel III (ATP III) and World Health Organization (WHO) diagnostic
      criteria. Insulin resistance was estimated by homeostasis model assessment (HOMA
      IR). RESULTS: The age-adjusted prevalence of the metabolic syndrome was 23% (95%
      CI 19-26%) by the ATP III definition and 28% (24-32%) by the WHO definition.
      Although the prevalence increased significantly with age and BMI in both sexes by
      both definitions, differences in estimates were noted. With ATP III, the age
      specific rates were similar for men and women aged 20-49 years but were
      significantly higher for women aged >/=50 years. With WHO, rates were higher for
      men than women aged 20-49 years and similar for those aged >/=50 years. The most
      common component of the metabolic syndrome in men and women was low HDL
      cholesterol with the ATP III and the presence of glucose intolerance and HOMA-IR
      with the WHO. Strong associations between HOMA-IR and individual components of
      the metabolic syndrome were observed. After fitting a model with HOMA-IR as the
      outcome, waist circumference, triglyceride level, and fasting plasma glucose
      level were significantly associated with HOMA-IR. CONCLUSIONS: The metabolic
      syndrome is common among Arab Americans and is related to modifiable risk
      factors.

PMID- 14693996
TI  - Concept, strategies, and feasibility of noninvasive insulin delivery.
AB  - OBJECTIVE: To comprehensively review the progress to date on the development of
      alternative routes for insulin delivery. RESEARCH DESIGN AND METHODS: Study data
      were collected through a Medline review. RESULTS: Proof of principle has been
      established for many routes of administration including dermal, nasal, oral,
      buccal, and pulmonary insulin delivery. CONCLUSIONS: Of all the approaches to
      date, pulmonary delivery appears to be most feasible. Ongoing phase III studies
      will ultimately determine safety, tolerability, and efficacy before approval for
      clinical use.

PMID- 14693997
TI  - Antihypertensive therapy and incidence of type 2 diabetes: a systematic review.
AB  - OBJECTIVE: To systematically review the available evidence examining the effects
      of the major antihypertensive drug classes on the incidence of type 2 diabetes.
      RESEARCH DESIGN AND METHODS: The Cochrane Controlled Trials Register, Medline,
      and Embase were searched for English-language case-control, cohort, and
      randomized controlled trials involving the major antihypertensive classes and
      reporting type 2 diabetes as an end point. Reference lists of original studies
      and narrative reviews were also hand searched. One reviewer (R.P.) performed the
      electronic searches. Both reviewers independently extracted data and assessed all
      potentially relevant studies for inclusion and methodological quality. Abstracts
      were not included, and unpublished studies were not sought. RESULTS: One case
      control study, 8 cohort studies, and 14 randomized controlled trials met
      inclusion criteria. No study examined diabetes incidence as a primary end point.
      Poor methodological quality limits the conclusions that can be drawn from most
      nonrandomized trials. Evidence from randomized studies is also potentially
      limited by several sources of bias, including treatment contamination and bias
      inherent in post hoc analyses. Data from the highest-quality studies suggest that
      diabetes incidence is unchanged or increased by thiazide diuretics and beta
      blockers and unchanged or decreased by ACE inhibitors, calcium channel blockers,
      and angiotensin receptor blockers. CONCLUSIONS: The major antihypertensive
      classes may exert differential effects on diabetes incidence, although current
      data are far from conclusive. Ongoing placebo-controlled randomized trials
      involving potentially beneficial drug classes and examining diabetes incidence as
      a primary end point should provide more definitive evidence.

PMID- 14693998
TI  - Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus
      statement from the American Heart Association and American Diabetes Association.

PMID- 14693999
TI  - Aspects of blood pressure, lipid, and glycemic treatment.

PMID- 14694000
TI  - A new dietary approach to reduce the risk of type 2 diabetes?

PMID- 14694001
TI  - Similar A1C outcomes in type 1 diabetic patients undergoing intensive diabetes
      management with preprandial rapid-acting insulin and either CSII or glargine.

PMID- 14694002
TI  - Plasma interleukin-18 concentrations are elevated in type 2 diabetes.

PMID- 14694003
TI  - Matrix metalloproteinase 2 may be a marker of microangiopathy in children and
      adolescents with type 1 diabetes.

PMID- 14694004
TI  - Plasma adiponectin and pregnancy-induced insulin resistance.

PMID- 14694005
TI  - Vitiligo associated with subcutaneous insulin lispro infusion in type 1 diabetes.

PMID- 14694006
TI  - Aseptic peritonitis revealed through recurrent catheter obstructions in type 1
      diabetic patients treated with continuous peritoneal insulin infusion.

PMID- 14694007
TI  - Comparative study of prognostic value for coronary disease risk between the U.K.
      prospective diabetes study and Framingham models.

PMID- 14694008
TI  - The biological variation of sex hormone-binding globulin in type 2 diabetes:
      implications for sex hormone-binding globulin as a surrogate marker of insulin
      resistance.

PMID- 14694009
TI  - Development of an assessment tool for screening children for glucose intolerance
      by oral glucose tolerance test.

PMID- 14694010
TI  - Vinegar improves insulin sensitivity to a high-carbohydrate meal in subjects with
      insulin resistance or type 2 diabetes.

PMID- 14694011
TI  - Sleep disturbance and onset of type 2 diabetes.

PMID- 14694012
TI  - Non-HDL cholesterol contributes to the "hypertriglyceridemic waist" as a
      cardiovascular risk factor: the Hoorn study.

PMID- 14694013
TI  - Improvement of temperature and flow in feet of subjects with diabetes with use of
      a transdermal preparation of L-arginine: a pilot study.

PMID- 14694014
TI  - Increased prevalence of enteroviral RNA in blood spots from newborn children who
      later developed type 1 diabetes: a population-based case-control study.

PMID- 14694015
TI  - Physician attitudes toward foot care education and foot examination and their
      correlation with patient practice.

PMID- 14694016
TI  - Hepatocyte growth factor in the vitreous fluid of patients with proliferative
      diabetic retinopathy: its relationship with vascular endothelial growth factor
      and retinopathy activity.

PMID- 14694017
TI  - Autoimmune hypoglycemia in a type 2 diabetic patient with anti-insulin and
      insulin receptor antibodies.

PMID- 14694018
TI  - Phenotypic heterogeneity and associations of two aldose reductase gene
      polymorphisms with nephropathy and retinopathy in type 2 diabetes: response to
      Wang et al.

PMID- 14694022
TI  - Ethics and politics of research involving subjects with impaired decision-making
      abilities.

PMID- 14694023
TI  - Angioplasty for intracranial atherosclerosis: is the treatment worse than the
      disease?

PMID- 14694024
TI  - Are the rules for research with subjects with dementia changing?: views from the
      field.
AB  - Deliberative bodies have recommended additional protections for persons with
      dementia included in clinical trials. This survey of experienced dementia
      researchers revealed that 45 to 64% considered that specific ones of these
      recommendations would increase subject protection, and 40 to 86% considered they
      would make research less feasible. The real tradeoff between protection and
      difficulty in conducting research on devastating illnesses needs to be confronted
      when new regulations in this area are debated.

PMID- 14694025
TI  - Treatment of autoimmune myasthenia gravis.
AB  - Autoimmune myasthenia gravis (MG) is associated with antibodies directed against
      the nicotinic acetylcholine receptor (AChR) in 85% of patients. Other
      postsynaptic neuromuscular junction antigens are implicated, e.g., muscle
      specific receptor tyrosine kinase (MuSK), in a number of the remaining 15% of
      patients, so-called seronegative MG. The autoimmune attack generally leads to
      decreased concentrations of the AChR and damage to the structure of the endplate
      itself. This information has guided the empiric treatment of patients with MG and
      has suggested new treatment strategies. Whereas the outcome of patients with MG
      has improved because of more effective symptomatic treatment, including advances
      in critical care medicine and the use of cholinesterase inhibitors, the greatest
      advances have come from therapies that directly reduce the autoimmune attack or
      modify its effects on the AChR and the surrounding endplate. Immune-directed
      treatment of patients with MG, which is guided by this information and by data
      from the management of other autoimmune disease, is aimed at inducing an
      immunologic remission and then maintaining that remission. Remission induction is
      usually accomplished through the use of high-dose corticosteroids, frequently in
      conjunction with IV immunoglobulin or plasmapheresis. Maintenance of the
      remission is usually accomplished by slow tapering of the corticosteroids along
      with the use of "steroid-sparing" agents, which include azathioprine, thymectomy,
      and possibly mycophenolate. Therapy usually begins with cholinesterase
      inhibitors. If necessary, immune-directed treatment is added, beginning with
      either thymectomy or high-dose corticosteroids. The short-term therapies, i.e.,
      IV immunoglobulin or plasmapheresis, may be effective in the early stages of
      treatment or later during an exacerbation. Steroid-sparing medications are
      usually added to facilitate the tapering phase.

PMID- 14694026
TI  - Understanding of informed consent by demented individuals.
AB  - BACKGROUND: The informed consent process is central to the conduct of research
      but may be difficult for cognitively impaired participants to understand. The
      authors developed a brief test addressing the elements of informed consent for a
      specific minimum-risk nontreatment research protocol. OBJECTIVE: To evaluate and
      document understanding of informed consent by elderly research participants
      across a range of dementia severity. METHODS: The elements of informed consent
      regarding participation in a longitudinal study of healthy aging and dementia
      were reviewed with both demented (n = 250) and nondemented (n = 165) participants
      who then completed a short test requiring yes-no responses to assess
      understanding of these elements. Demented participants had very mild, mild, or
      moderate dementia as staged by the Clinical Dementia Rating. RESULTS: After
      adjusting for education, performance on the test varied with dementia severity in
      mean differences and by correlation. All nondemented and very mildly demented
      participants and 92% of mildly demented participants provided correct answers for
      at least 8 of 10 true-false items, whereas only 67% of the moderately demented
      participants achieved this level of accuracy. CONCLUSIONS: Demented individuals,
      very mild and mild, understood informed consent information for this nontreatment
      research study. Understanding notably declined in the moderate stage of dementia.
      Brief tests may be useful as one method to assess understanding of the consent
      process for specific studies.

PMID- 14694027
TI  - Low blood pressure and the risk of dementia in very old individuals.
AB  - BACKGROUND: The role of blood pressure (BP) as a risk factor for dementia is
      complex and may be age dependent. In very old individuals, low BP might increase
      risk for dementia, perhaps by reducing cerebral perfusion pressure. METHODS: The
      association between BP and dementia was examined in the Bronx Aging Study, a
      prospective study of 488 community-dwelling elderly individuals over age 75,
      dementia-free at baseline (1980 to 1983) and followed at 12- to 18-month
      intervals. Subjects with baseline BP and with at least one follow-up visit were
      included (n = 406). Incident dementia was diagnosed using the criteria of the
      Diagnostic and Statistical Manual of Mental Disorders (3rd rev. ed.). RESULTS:
      Over 21 years (median 6.7 years), 122 subjects developed dementia (65 Alzheimer's
      disease [AD], 28 vascular dementia, 29 other dementias). Relative risk of
      dementia increased for each 10-mm Hg decrement in diastolic (hazard ratio [HR]
      1.20, 95% CI 1.03 to 1.40) and mean arterial (HR 1.16, 95% CI 1.02 to 1.32)
      pressure, adjusted for age, sex, and education. Low diastolic BP significantly
      influenced risk of developing AD but not vascular dementia. Upon examination of
      groups defined by BP, mildly to moderately raised systolic BP (140 to 179 mm Hg)
      was associated with reduced risk for AD (HR vs normal systolic BP group 0.55, 95%
      CI 0.32 to 0.96), whereas low diastolic BP (<or=70 mm Hg) was associated with
      increased risk of AD (HR vs normal diastolic BP group 1.91, 95% CI 1.05 to 3.48).
      Subjects with persistent low BP over 2 years had higher risk of developing
      dementia (HR 2.19, 95% CI 1.27 to 3.77). CONCLUSIONS: Low diastolic pressure is
      associated with higher risk of dementia in elderly individuals over age 75.
      Dementia risk was higher in subjects with persistently low BP.

PMID- 14694028
TI  - Temporal cortex hypermetabolism in Down syndrome prior to the onset of dementia.
AB  - BACKGROUND: Adults with Down syndrome (DS) are at increased risk for dementia and
      provide an opportunity to identify patterns of brain activity that may precede
      dementia. Studies of early Alzheimer's disease (AD) and risk of AD show decreased
      function in posterior cingulate and temporal cortex as initial indicators of the
      disease process, but whether the origin and sequence of predementia brain changes
      are the same in DS is unknown. METHODS: The regional cerebral glucose metabolic
      rates (GMR) among middle-aged nondemented people with DS (n = 17), people with
      moderate AD (n = 10), and age-matched control subjects (n = 24) were compared
      using PET during a cognitive task. RESULTS: Statistical parametric mapping
      conjunction analyses showed that 1) both DS and AD groups had lower GMR than
      their respective controls primarily in posterior cingulate and 2) compared with
      respective controls, the subjects with DS had higher GMR in the same areas of
      inferior temporal/entorhinal cortex where the AD subjects had lower GMR. The same
      results were replicated after 1 year of follow-up. CONCLUSIONS: As the DS
      subjects were not clinically demented, inferior temporal/entorhinal cortex
      hypermetabolism may reflect a compensatory response early in disease progression.
      Compensatory responses may subsequently fail, leading to neurodegenerative
      processes that the authors anticipate will be detectable in vivo as future GMR
      decreases in inferior temporal/entorhinal cortex are accompanied by clinical
      signs of dementia.

PMID- 14694029
TI  - Initial outcomes in the Multicenter Study of Epilepsy Surgery.
AB  - OBJECTIVE: To obtain prospective data regarding seizures, anxiety, depression,
      and quality of life (QOL) outcomes after resective epilepsy surgery. METHODS: The
      authors characterized resective epilepsy surgery patients prospectively at yearly
      intervals for seizure outcome, QOL, anxiety, and depression, using standardized
      instruments and patient interviews. RESULTS: Of 396 patients who underwent
      resective surgical procedures, 355 were followed for at least 1 year. Of these,
      75% achieved a 1-year remission at some time during follow-up; patients with
      medial temporal (77%) were more likely than neocortical resections (56%) to
      achieve remission (p = 0.01). Relapse occurred in 59 (22%) patients who remitted,
      more often in medial temporal (24%) than neocortical (4%) resected patients (p =
      0.02). QOL, anxiety, and depression all improved dramatically within 3 months
      after surgery (p < 0.0001), with no significant difference based on seizure
      outcome. After 3 months, QOL in seizure-free patients further improved gradually,
      and patients with seizures showed gradual declines. By 12 and 24 months, overall
      QOL and its epilepsy-targeted and physical health domains were significantly
      different in the two outcome groups. (Anxiety and depression scores also
      gradually diverged, with improvements in seizure-free and declines in continued
      seizure groups, but differences were not significant.) CONCLUSION: Resective
      surgery for treatment of epilepsy significantly reduces seizures, most strikingly
      after medial temporal resection (77% 1 year remission) compared to neocortical
      resection (56% 1 year remission). Resective epilepsy surgery has a gradual but
      lasting effect on QOL, but minimal effects on anxiety and depression. Longer
      follow-up will be essential to determine ultimate seizure, QOL, and psychiatric
      outcomes of epilepsy surgery.

PMID- 14694030
TI  - Seizure identification by clinical description in temporal lobe epilepsy: how
      accurate are we?
AB  - OBJECTIVE: To determine the accuracy of the clinical history performed by
      epileptologists in the identification of seizures in patients with suspected
      temporal lobe epilepsy. METHODS: The clinical and EEG telemetry (EEGT) monitoring
      data of 88 patients with suspected refractory temporal lobe seizures referred for
      evaluation of epilepsy surgery were prospectively evaluated. All clinical events
      obtained by history in these patients were adjudicated as being a seizure or not
      by two blinded (without access to EEG data) independent epileptologists. Each
      clinical event was then matched with the corresponding clinical event recorded
      with EEG telemetry in the epilepsy monitoring unit (gold standard). Sensitivity,
      specificity, overall accuracy, predictive value, and interrater agreement for the
      clinical assessment were obtained. RESULTS: Of 357 clinically different events,
      175 (49%) were reproduced in the epilepsy monitoring unit. Only 10 events were
      misidentified by history as being a seizure or not, resulting in an overall
      clinical accuracy of 94%. Epileptologists' sensitivity for seizure identification
      was 96% (95% CI 92, 98%) but specificity was only 50% (95% CI 22, 79%). Accuracy
      for complex partial seizures and generalized seizures was higher than for simple
      partial seizures (SPS). Misidentification occurred only with SPS and nonepileptic
      events. Agreement beyond chance among epileptologists was good. CONCLUSION: In
      this selected group of patients with temporal lobe epilepsy, seizure
      identification by clinical history is highly accurate. Epileptologists rarely
      miss seizures (high sensitivity) but more often overcall nonepileptic events as
      seizures (low specificity).

PMID- 14694031
TI  - Peripheral retinal dysfunction in patients taking vigabatrin.
AB  - OBJECTIVE: To assess the wide-field multifocal electroretinogram (WF-mfERG) for
      assessment of retinal function in vigabatrin-treated patients. METHODS: Thirty
      two adults who had taken vigabatrin for at least 3 years for localization-related
      epilepsy underwent WF-mfERG, ERG, logMar visual acuity and color vision
      evaluation, Humphrey visual field analysis (static perimetry), and funduscopy.
      The group was matched with a cohort of patients who had never received
      vigabatrin. Results were compared with a normative data set (120 drug-free
      controls) with respect to potential bilateral abnormalities in response timing.
      RESULTS: There were no significant differences between groups in visual acuity or
      color vision testing. Of the vigabatrin patients, 19 (59%) had bilateral visual
      field defects compared to none of the controls. Using WF-mfERG, all patients on
      vigabatrin with visual field defects showed abnormalities (100% sensitivity) and
      only 2 of the 13 patients without a field defect showed retinal abnormalities
      (86% specificity). CONCLUSIONS: WF-mfERG may be useful for detecting retinal
      pathology in patients taking vigabatrin. The majority of previous reports based
      on subjective testing may have underestimated the prevalence of peripheral
      retinal toxicity related to the drug.

PMID- 14694032
TI  - Interaction of atherosclerosis and inflammation in elderly subjects with poor
      cognitive function.
AB  - OBJECTIVE: To test the hypothesis that a pro-inflammatory response is associated
      with cognitive impairment among individuals with cardiovascular disease. METHOD:
      All 85-year-old inhabitants of Leiden (n = 599) were visited at their place of
      residence. A history of cardiovascular disease and an EKG were used as indicators
      of atherosclerosis. Production of the pro-inflammatory cytokine tumor necrosis
      factor-alpha and the anti-inflammatory cytokine interleukin-10 was assessed in a
      whole-blood assay using lipopolysaccharide as a stimulus. Global cognitive
      functioning was determined with the Mini-Mental State Examination (MMSE);
      attention, cognitive speed, and memory were determined with four
      neuropsychological tests; and a history of dementia was obtained. RESULTS: In
      subjects with cardiovascular disease, median MMSE scores were lower in those with
      a pro-inflammatory response when compared with those with an anti-inflammatory
      response (p = 0.02). Similar associations were found for the Stroop Test,
      measuring attention (p < 0.01), the Coding Test measuring cognitive speed (p =
      0.02), the Word Learning Test measuring memory (p < 0.01), and the presence of
      dementia (p = 0.04). The associations remained unaltered after adjustments for
      possible confounders such as gender, level of education, use of nonsteroidal anti
      inflammatory drugs, use of cardiovascular drugs, and cardiovascular risk factors.
      In contrast, outcomes of the cognitive tests and presence of dementia were not
      dependent on the inflammatory response when cardiovascular disease was absent.
      CONCLUSION: The combination of cardiovascular disease and a pro-inflammatory
      cytokine response may be associated with cognitive impairment and dementia.

PMID- 14694033
TI  - Profile of cognitive progression in early Huntington's disease.
AB  - OBJECTIVE: To examine the pattern of cognitive decline in early Huntington's
      disease (HD). METHODS: The authors studied 61 patients with mild to moderate HD
      who had at least three annual neuropsychological assessments using the Core
      Assessment Program for Intracerebral Transplantation in Huntington's Disease
      short battery. A subset of 34 patients had additional neuropsychological tests,
      and another subset of 21 patients was assessed annually on the Cambridge
      Neuropsychological Test Automated Battery. Neuropsychological measures that
      changed significantly over time were submitted to a multiple analysis of
      covariance to explore associations with demographic and neurologic indices.
      RESULTS: Patients showed a progressive impairment in attention, executive
      function, and immediate memory, with timed tests of psychomotor skill being
      particularly sensitive to decline. In contrast, general cognition, semantic
      memory, and delayed recall memory were relatively unaffected. CONCLUSION: The
      profile of cognitive performance shows selective and progressive dysfunction of
      attention and executive function in patients with mild to moderate HD, consistent
      with frontostriatal pathology at this stage of disease.

PMID- 14694034
TI  - Patterns of cortical reorganization in complex regional pain syndrome.
AB  - OBJECTIVE: To use magnetoencephalography to assess possible cortical
      reorganization in the primary somatosensory cortex (S1) of patients with complex
      regional pain syndrome (CRPS). BACKGROUND: Patterns of pain and sensory symptoms
      in CRPS may indicate plastic changes of the CNS. METHODS: Magnetic source imaging
      was used to explore changes in the cortical representation of digits (D) 1 and 5
      in relation to the lower lip on the unaffected and affected CRPS side in 12
      patients. RESULTS: The authors found a significant shrinkage of the extension of
      the cortical hand representation for the CRPS affected side. The center of the
      hand was shifted toward the cortical representation of the lip. The cortical
      reorganization correlated with the amount of CRPS pain (r = 0.792), as measured
      by the McGill questionnaire, and the extent of mechanical hyperalgesia (r =
      0.860). Using multiple regression analysis, the best predictor for the plastic
      changes was found to be mechanical hyperalgesia. Additionally, S1 sources
      following tactile stimulation were significantly increased on the CRPS side
      compared to the unaffected limb. CONCLUSIONS: This study showed reorganization of
      the S1 cortex contralateral to the CRPS affected side. The reorganization
      appeared to be linked to complaints of neuropathic pain.

PMID- 14694035
TI  - Hippocampal volume deficits in alcoholic Korsakoff's syndrome.
AB  - OBJECTIVE: To examine whether the amnesic syndrome of alcoholic Korsakoff's
      syndrome (KS) originates from pathology of the hippocampus and not solely the
      diencephalon. METHODS: The authors studied 5 patients with KS and two comparison
      groups: 20 patients with Alzheimer's disease (AD) with known bilateral
      hippocampal volume loss and 36 healthy control subjects. The authors used
      quantitative MRI to characterize the hippocampus and comparison brain structures
      (temporal cortex, lateral ventricles, temporal horns, and third ventricle).
      RESULTS: Relative to healthy control subjects, the KS and AD groups had
      comparable, significant bilateral hippocampal volume deficits. Although both
      patient groups also had extensive volume abnormalities in temporal lobe cortical
      gray matter, temporal horns, and lateral and third ventricles, declarative memory
      test performance was selectively related to hippocampal volumes in KS and not to
      any of the comparison volumes. CONCLUSIONS: The characteristic memory deficit of
      Korsakoff's syndrome involves hippocampal and diencephalic pathology.

PMID- 14694036
TI  - Neurofilament light protein and glial fibrillary acidic protein as biological
      markers in MS.
AB  - OBJECTIVE: To determine if CNS-derived proteins present in the CSF of multiple
      sclerosis (MS) patients reflect different pathologic processes of MS and if these
      proteins could be useful as biologic markers of disease activity. METHODS:
      Concentrations of the neurofilament light protein (NFL), glial fibrillary acidic
      protein (GFAP), S100B, and the neuron-specific enolase protein (NSE) were
      determined in the CSF of 66 MS patients and 50 healthy control subjects with
      immunoassays. RESULTS: The mean levels of the NFL were increased during all
      stages of MS compared with controls (p < 0.001), peaking almost 10 times higher
      during acute relapses. The highest levels of GFAP were found during the secondary
      progressive course (p < 0.001) with a strong correlation with neurologic deficits
      (Expanded Disability Status Scale score, r = 0.73, p < 0.001). No increase of
      S100B or NSE protein was found in the CSF of MS patients compared with control
      subjects. CONCLUSIONS: Increased level of NFL is a general feature of MS,
      indicating continuous axonal damage during the entire course of the disease with
      the most profound damage during acute relapses. GFAP may serve as a biomarker for
      disease progression, probably reflecting the increasing rate of astrogliosis.

PMID- 14694037
TI  - Neurofibromatosis type 1: motor and cognitive function and T2-weighted MRI
      hyperintensities.
AB  - BACKGROUND: Cognitive impairment and fine motor deficits are frequent
      manifestations in patients with neurofibromatosis type 1 (NF1). More than 50% of
      patients with NF1 show focal areas of high signal intensity (T2H) on T2-weighted
      MRI of the brain. It has been hypothesized that T2H may be associated with the
      cognitive and motor problems. METHODS: The authors investigated 100 patients with
      NF1 and 100 healthy control subjects matched for age, sex, and socioeconomic
      status for their IQ (Wechsler Intelligence Scale for Children-Revised [WISC-R]
      and Wechsler Adult Intelligence Scale-Revised [WAIS-R]), fine motor abilities
      (Motorische Leistungs-Serie [motor performance task]), and T2H (MRI). RESULTS: As
      a group, the 100 patients performed within normal limits of WISC-R and WAIS-R
      scores. However, the scores for the NF1 patients with normal MRI were at the
      mean, whereas those for the patients who had T2H (n = 58) were significantly
      depressed. On measures of fine motor skills, patients with T2H performed poorer
      than patients with normal MRI. CONCLUSION: Hyperintensities on T2-weighted MRI
      represent a biological marker for impaired cognitive and fine motor performance
      in patients with NF1.

PMID- 14694038
TI  - Urgent endovascular revascularization for symptomatic intracranial
      atherosclerotic stenosis.
AB  - BACKGROUND: Endovascular revascularization for intracranial atherosclerotic
      stenoses is being increasingly performed at major medical centers and has been
      reported to be technically feasible and safe. The authors report their experience
      with patients who underwent such a procedure for impending stroke and neurologic
      instability. METHOD: All 18 patients (21 intracranial lesions) treated between
      1997 and 2002 at the authors' institution with endovascular revascularization
      were retrospectively reviewed. Each patient had failed maximal medical therapy
      and was thought to be at high risk for an imminent stroke. RESULTS: Endovascular
      revascularization was performed on eight distal internal carotid artery lesions,
      six middle cerebral artery lesions, four intracranial vertebral artery lesions,
      and three basilar artery lesions. Recanalization was complete in 5 arteries
      (Thrombolysis in Myocardial Infarction [TIMI] Grade III), partial in 14 arteries
      (TIMI Grade II), and complete occlusion (TIMI 0) developed in 1 artery. In a
      patient with a tight basilar stenosis, no angioplasty could be performed because
      of the inability to cross the stenosis with the guidewire. Major periprocedural
      complications occurred in 9 (50%) patients: intracranial hemorrhage in 3 (17%),
      disabling ischemic stroke in 2 (11%), and major extracranial hemorrhage in 4
      (22%). Three patients died: one from intracerebral hemorrhage and two from
      cardiorespiratory failure. CONCLUSIONS: Endovascular revascularization of
      intracranial vessels is technically feasible and may be performed successfully.
      However, periprocedural complication and fatality rates in neurologically
      unstable patients are high. The results suggest that patient selection, procedure
      timing, and periprocedural medical management are critical factors to reduce
      periprocedural morbidity and mortality.

PMID- 14694039
TI  - Intracranial arterial dolichoectasia and its relation with atherosclerosis and
      stroke subtype.
AB  - OBJECTIVE: To investigate the relationship between intracranial arterial
      dolichoectasia (IADE) and vascular risk factors, atherosclerosis of the carotid
      arteries as measured by ultrasound scan, and stroke subtypes. METHODS: The sample
      consists of 510 consecutively recruited patients with brain infarction confirmed
      by MRI. The diagnosis of IADE was made by consensus between two neurologists
      based on MRI results. An independent reading of the 510 scans was made, with
      measurement of the diameter of the seven main intracranial arteries with a 16
      diopter lens to validate the consensus and to better characterize patients with
      IADE. RESULTS: Sixty-three IADE(+) patients were identified by consensus (12%),
      of whom 59 (94%) had at least one intracranial artery in the fourth quartile of
      the distribution of diameters of intracranial arteries. Multivariate analyses
      found an association between IADE(+) and age (OR [95% CI] 1.04 [1.01-1.08]), male
      sex (3.31 [1.67-6.55]), hypertension (1.94 [1.01-3.72]), and previous myocardial
      infarction (2.68 [1.33-5.38]). There was no association between IADE and carotid
      atherosclerosis markers such as plaque or intima-media thickening. Lacunar
      infarct was more frequent in patients with IADE (36% versus 19%), with an
      adjusted OR of 2.89 (95% CI 1.29-6.46) compared with atherothrombotic infarct.
      CONCLUSIONS: IADE was associated with vascular risk factors such as age, male
      sex, hypertension, previous history of myocardial infarction, and lacunar
      infarct, but not with carotid atherosclerosis.

PMID- 14694040
TI  - Presynaptic failure of neuromuscular transmission and synaptic remodeling in EA2.
AB  - OBJECTIVE: To further investigate the basis of abnormal neuromuscular
      transmission in two patients with congenital myasthenic syndrome associated with
      episodic ataxia type 2 (EA2) using stimulated single fiber EMG (SFEMG) and in
      vitro microelectrode studies. METHODS: Two patients with genetically
      characterized EA2 previously shown to have abnormal neuromuscular transmission by
      voluntary SFEMG were studied with stimulated SFEMG and anconeus muscle biopsy
      with microelectrode studies and electron microscopy of the neuromuscular
      junction. RESULTS: In vivo stimulated SFEMG showed signs of presynaptic failure,
      with jitter and blocking that improved with increased stimulation frequency.
      Additional evidence of presynaptic failure was provided by the in vitro
      microelectrode studies, which showed marked reduction of the end plate potential
      quantal content in both patients. Of note, the end plate potentials showed high
      sensitivity to N-type blockade with omega-conotoxin not seen in controls. The
      ultrastructural studies revealed some evidence of small nerve terminals apposed
      to normal or mildly overdeveloped postsynaptic membranes, suggesting an ongoing
      degenerative process. CONCLUSIONS: The authors demonstrated presynaptic failure
      of neurotransmission in patients with heterozygous nonsense mutations in CACNA1A.
      The contribution of non-P-type calcium channels to the process of
      neurotransmitter release in these patients likely represents a compensatory
      mechanism, which is insufficient to restore normal neuromuscular transmission.

PMID- 14694041
TI  - Subclinical vestibulocerebellar dysfunction in migraine with and without aura.
AB  - OBJECTIVE: In patients with migraine, neurotologic symptoms and signs occur
      commonly. The authors' aim was to determine whether neurotologic findings are in
      accordance with the type of migraine and whether test findings differ from those
      of healthy controls. METHODS: The authors examined 36 patients with various types
      of migraine classified by International Headache Society criteria. Comprehensive
      neurotologic tests were performed between attacks: video-oculography (VOG),
      electronystagmography, static posturography, and audiometry on 12 patients with
      migraine with aura (MA) and 24 patients with migraine without aura (MO). Results
      were compared to those of test-specific nonmigrainous control groups. Only eight
      migraineurs (six with MA and two with MO) had vertigo or dizziness. RESULTS:
      Despite the absence of clinical neurotologic symptoms, most of the patients with
      migraine (83%) showed abnormalities in at least one of these tests. Both migraine
      types differed significantly from the control group (in VOG, in saccadic
      accuracy, and in static posturography). Vestibular findings tended to be more
      severe in MA than in MO. CONCLUSIONS: These data suggest that interictal
      neurotologic dysfunction in MA and MO share similar features and that the
      defective oculomotor function is mostly of vestibulocerebellar origin.

PMID- 14694042
TI  - Gabapentin in the prophylaxis of chronic daily headache: a randomized, placebo
      controlled study.
AB  - OBJECTIVE: To compare efficacy and safety of gabapentin (GPT) versus placebo for
      prophylaxis of chronic daily headache (CDH) (headache at least 15 days/month of
      greater than 4 hours duration over preceding 6 months). METHODS: This is a
      multicenter randomized placebo-controlled crossover study. After 4-week baseline,
      subjects, aged 18 to 65, were randomized to GPT 2,400 mg/day or placebo. There
      was 2 weeks titration, 6-week stable dosage, and 1 week washout period between
      treatment arms. The primary efficacy measure was the difference between the
      percentage of headache-free days per treatment period. Secondary efficacy
      measures included headache duration and severity, degree of disability,
      associated symptoms, concomitant medications, Visual Analogue Scale (VAS) scores,
      and quality of life (QOL). RESULTS: A total of 133 patients were enrolled (41
      men, 92 women, mean age 43 years). All were eligible for safety analysis. Ninety
      five received sufficient treatment to allow evaluation of efficacy. There was a
      9.1% difference in headache-free rates favoring GPT over placebo (p = 0.0005).
      Benefits for GPT were also demonstrated for headache-free days/month (p =
      0.0005), severity (p = 0.03), VAS (p = 0.0006), headache-associated symptoms of
      nausea (p = 0.03) and photophobia/phonophobia (p = 0.04), disability affecting
      normal activities (p = 0.02), attacks requiring bed rest (p = 0.001), and QOL
      related to bodily function (p = 0.01), health/vitality (p = 0.0001), social
      function (p = 0.006), and health transition (p = 0.0002). Reduction in headache
      days/month was seen across the spectrum of prerandomization headache frequencies.
      CONCLUSION: Gabapentin represents a therapeutic option for chronic daily
      headache.

PMID- 14694043
TI  - Identification of a novel SCA14 mutation in a Dutch autosomal dominant cerebellar
      ataxia family.
AB  - OBJECTIVE: To report a Dutch family with autosomal dominant cerebellar ataxia
      (ADCA) based on a novel mutation in the PRKCG gene. METHODS: The authors studied
      13 affected members of the six-generation family. After excluding the known
      spinocerebellar ataxia (SCA) genes, a combination of the shared haplotype
      approach, linkage analysis, and genealogic investigations was used. Exons 4 and 5
      of the candidate gene, PRKCG, were sequenced. RESULTS: Affected subjects
      displayed a relatively uncomplicated, slowly progressive cerebellar syndrome,
      with a mean age at onset of 40.8 years. A focal dystonia in two subjects with an
      onset of disease in their early 20s suggests extrapyramidal features in early
      onset disease. Significant linkage to a locus on chromosome 19q was found,
      overlapping the SCA-14 region. Based on the recent description of three missense
      mutations in the PRKCG gene, located within the boundaries of the SCA-14 locus,
      we sequenced exons 4 and 5 of this gene and detected a novel missense mutation in
      exon 4, which involves a G-->A transition in nucleotide 353 and results in a
      glycine-to-aspartic acid substitution at residue 118. CONCLUSION: A SCA-14-linked
      Dutch ADCA family with a novel missense mutation in the PRKCG gene was
      identified.

PMID- 14694044
TI  - Microtubule-associated tau protein positive neuronal and glial inclusions in ALS.
AB  - BACKGROUND: The authors compared tau protein deposition in the frontal cortex of
      patients with cognitive impairment of amyotrophic lateral sclerosis (ALSci) (n =
      6), cognitively intact patients with ALS (n = 6), and age-matched controls (n =
      6) in order to determine the pathologic substrate of ALSci. METHODS: Archival
      paraffin-embedded tissue was examined using Gallyas staining and immunostaining
      for tau-1 (phosphorylation-dependent tau epitope), tau-2 (phosphorylation
      independent), Alzheimer-specific tau phosphoepitopes (AT 8; ser(396)
      phosphorylation), beta-amyloid, glial fibrillary acid protein, SMI 31
      (recognizing phosphorylated NFH), alpha-synuclein, or ubiquitin. RESULTS: Tau
      immunoreactive astrocytic and dense neuronal inclusions were found in both ALS
      and ALSci, although to a greater extent in ALSci. Superficial linear spongiosis
      and Gallyas-positive intraneuronal aggregates, immunoreactive with tau-1 and AT 8
      but rarely to ser(396) tau, were unique to ALSci. Dense extracellular aggregates
      were observed by both Gallyas staining and tau-1 immunostaining. Tufted
      degenerating astrocytes containing tau-1 and AT 8 immunoreactive aggregates and,
      rarely, dense Gallyas positive neuritic plaques immunoreactive with tau-1 and AT
      8, but not with ser(396) tau or beta-amyloid, were observed in ALSci. Tau
      positive glial coiled bodies were observed in the deep cortical layers and
      adjacent subcortical white matter in ALSci. Although 3R and 4R tau mRNA isoforms
      were expressed to similar levels in the frontal cortex of all cases, the total
      amount of tau mRNA was increased in both ALS and ALSci. Both gray and white
      matter soluble tau protein expression was similar among control, ALS, and ALSci
      cases. CONCLUSIONS: Cognitive dysfunction in ALS may reflect abnormal tau protein
      metabolism.

PMID- 14694045
TI  - Cyclo-oxygenases and prostaglandins in acute inflammatory demyelination of the
      peripheral nerve.
AB  - OBJECTIVE: To investigate the expression of cyclo-oxygenases (COX), key enzymes
      in propagating inflammatory responses by converting arachidonic acid to
      prostaglandins, in inflammatory demyelinating disorders of the peripheral nervous
      system (PNS). METHODS: Expression and distribution of COX messenger RNA (mRNA)
      and protein were studied in sural nerve biopsies, serum, and CSF samples from
      patients with Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP), or, for comparison, with vasculitic neuropathy
      (VN), which is a inflammatory nondemyelinating disorder, and noninflammatory
      neuropathies (NIN) using RT-PCR, immunohistochemistry, and immunoblotting. To
      confirm functional COX-2 activity, the expression of prostaglandin E(2) (PGE(2))
      and prostaglandin F(2alpha) (PGF(2alpha)) was evaluated by ELISA ex vivo and in
      vitro. RESULTS: Whereas COX-1 expression was unaltered in all investigated
      groups, a significant upregulation of COX-2 mRNA was detected in sural nerves
      from patients with GBS, CIDP, or VN but not in control subjects with
      noninflammatory disorders. Macrophages were identified as its primary cellular
      source. Increased COX-2 protein levels were detectable in serum and CSF from all
      patients with GBS and, in smaller numbers only, in samples from patients with
      CIDP or VN but not from the NIN group studied. Moreover, increased levels of
      PGE(2) and PGF(2alpha) were measurable in sera from patients with GBS, CIDP, or
      VN and in cell culture supernatants from in vitro stimulated macrophages,
      indicative of COX-2 activity. CONCLUSIONS: Cyclo-oxygenase-2, expressed by
      macrophages, may generate prostaglandins during acute inflammatory demyelination
      of the peripheral nerve.

PMID- 14694046
TI  - Muscle weakness in critically ill children.
AB  - OBJECTIVE: To establish the incidence of muscle weakness in critically ill
      children. METHODS: Neuromuscular examinations were performed in 830 children
      without identified antecedent or acute neuromuscular disease (age 3 months to 17
      years 11 months) admitted for >24 hours to a pediatric intensive care unit (ICU)
      over a 1-year period. RESULTS: Fourteen of 830 (1.7%) patients had generalized
      weakness. Four failed repeated attempts to extubate. Multiple organ dysfunction
      occurred in 11 patients and sepsis in 9. Most children received corticosteroids,
      neuromuscular blocking agents, or aminoglycoside antibiotics. Eight of the 14
      children were solid organ or bone marrow transplant recipients. Muscle biopsy
      showed evidence of acute quadriplegic myopathy in all three patients in whom
      biopsy was performed. Three patients died. In survivors, significant weakness
      persisted for 3 to 12 months following ICU discharge. CONCLUSIONS: Muscle
      weakness is an infrequent but significant feature of critical illness in
      children. Transplant recipients seem to be at particular risk.

PMID- 14694047
TI  - MRI findings in Susac's syndrome.
AB  - BACKGROUND: Susac syndrome (SS) is a self-limited syndrome, presumably
      autoimmune, consisting of a clinical triad of encephalopathy, branch retinal
      artery occlusions, and hearing loss. All three elements of the triad may not be
      present or recognized, and MR imaging is often necessary to establish the
      diagnosis. OBJECTIVE: To determine the spectrum of abnormalities on MRI in SS.
      METHODS: The authors reviewed the MR images of 27 previously unreported patients
      with the clinical SS triad, and 51 patients from published articles in which the
      MR images were depicted or reported. RESULTS: All 27 patients had multifocal
      supratentorial white matter lesions including the corpus callosum. The deep gray
      nuclei (basal ganglia and thalamus) were involved in 19 (70%). Nineteen (70%)
      also had parenchymal enhancement and 9 (33%) had leptomeningeal enhancement. Of
      the 51 cases from the literature, at least 32 had callosal lesions. The authors
      could not determine the presence of callosal lesions in 18 of these patients, and
      only one was reported to have a normal MRI at the onset of encephalopathy.
      CONCLUSIONS: The MR scans in SS show a rather distinctive pattern of
      supratentorial white matter lesions that always involve the corpus callosum.
      There is often deep gray matter, posterior fossa involvement, and frequent
      parenchymal with occasional leptomeningeal enhancement. The central callosal
      lesions differ from those in demyelinating disease, and should support the
      diagnosis of SS in patients with at least two of the three features of the
      clinical triad.

PMID- 14694048
TI  - Coagulopathy after snake envenomation.

PMID- 14694049
TI  - Efficacy of the Atkins diet as therapy for intractable epilepsy.
AB  - The ketogenic diet is effective for treating seizures in children with epilepsy.
      The Atkins diet can also induce a ketotic state, but has fewer protein and
      caloric restrictions, and has been used safely by millions of people worldwide
      for weight reduction. Six patients, aged 7 to 52 years, were started on the
      Atkins diet for the treatment of intractable focal and multifocal epilepsy. Five
      patients maintained moderate to large ketosis for periods of 6 weeks to 24
      months; three patients had seizure reduction and were able to reduce
      antiepileptic medications. This provides preliminary evidence that the Atkins
      diet may have a role as therapy for patients with medically resistant epilepsy.

PMID- 14694050
TI  - Frequency of epilepsy in patients with psychogenic seizures monitored by video
      EEG.
AB  - This study examined the frequency of epilepsy in a consecutive series of patients
      who received a definitive diagnosis of psychogenic nonepileptic seizures (PNES)
      after completing inpatient video-EEG (VEEG) monitoring. Of the 1,590 patients
      receiving definitive diagnosis, 514 (32.3%) were diagnosed with PNES. Twenty-nine
      (5.3%) of these patients were found to have both PNES and epilepsy. When strict
      diagnostic criteria are applied, there is little overlap between epileptic
      seizures and PNES among patients referred for VEEG monitoring.

PMID- 14694051
TI  - Idiopathic generalized epilepsy and choice of antiepileptic drugs.
AB  - The authors reviewed 58 patients with EEG-confirmed idiopathic generalized
      epilepsy (IGE). When initially seen, 17 (29%) were on broad-spectrum (adequate)
      antiepileptic drugs (AED) only, 28 (48%) on ill-advised AED only, and 13 (22%) on
      a combination of both. Thus, a majority of patients with IGE initially receive
      ill-advised AED, which cause IGE to appear intractable.

PMID- 14694052
TI  - The prognostic value of cognitive functioning in the survival of patients with
      high-grade glioma.
AB  - The authors studied cognitive functioning as a potential predictor of survival in
      68 newly diagnosed patients with high-grade glioma. In a combined Cox
      proportional hazards model, the influence of tumor, treatment, and patient
      characteristics, including cognitive functioning, was studied. Older age and
      higher tumor grade were associated with poorer survival. Although cognitive
      impairment was not found to be an independent prognostic factor for the entire
      sample, it was associated with significantly poorer survival among older patients
      with World Health Organization grade IV gliomas. Assessment of cognitive
      functioning in these patients may improve clinical decision making and thus
      quality of treatment.

PMID- 14694053
TI  - Malformations of cortical development in neurofibromatosis type 1.
AB  - The authors report three patients with neurofibromatosis type 1 and different
      types of malformations of cortical development: Patient 1 had a possible
      transmantle cortical dysplasia involving the right temporoinsuloparieto-occipital
      areas; Patient 2 had a periventricular band of heterotopic gray matter with an
      overlying pachygyric cerebral cortex; and Patient 3 had a left perisylvian
      polymicrogyria. Because all of these lesions result from different pathogenetic
      mechanisms, neurofibromin may play a role during several stages of cortical
      development.

PMID- 14694054
TI  - Autosomal recessive, DYT2-like primary torsion dystonia: a new family.
AB  - The authors report the clinical characteristics of a Sephardic Jewish kindred
      with autosomal recessive DYT2-like primary torsion dystonia. Three siblings had
      childhood onset of limb dystonia, and slow progression to generalized dystonia
      with predominant cranio-cervical involvement. There were no other abnormal signs,
      apart from dystonia and jerky tremor over a 12-year follow-up. All investigations
      for other causes of primary and secondary dystonia had normal results.

PMID- 14694055
TI  - Prevalence of essential tremor: door-to-door neurologic exams in Mersin Province,
      Turkey.
AB  - Estimates of the prevalence of essential tremor (ET) are probably low because
      screening questionnaires have been used. The authors estimated the prevalence of
      ET in Mersin Province, Turkey, in 2,253 individuals aged >or=40 years, all of
      whom were examined by study neurologists. There were 89 ET cases (prevalence =
      4.0%, 95% CI = 3.2 to 4.8%). The prevalence of ET may be higher than previously
      estimated. This is important when defining the extent of the health care problem.

PMID- 14694056
TI  - Experience with immunomodulatory treatments in Rasmussen's encephalitis.
AB  - The authors investigated immunomodulatory treatments in 15 patients with
      Rasmussen encephalitis (RE) (14 with childhood and one with adolescent onset RE).
      Positive time-limited responses were obtained in 11 patients using variable
      combinations of corticosteroids, apheresis, and high-dose IV immunoglobulins.
      Although surgical exclusion of the affected hemisphere is the only treatment that
      halts disease progression, immunomodulation can be considered when early surgery
      is not feasible, in late-onset patients with slower disease progression, and in
      the few cases of bilateral disease.

PMID- 14694057
TI  - Patient homozygous for a recessive POLG mutation presents with features of MERRF.
AB  - Both dominant and recessive missense mutations were recently reported in the gene
      encoding the mitochondrial DNA polymerase gamma (POLG) in patients with
      progressive external ophthalmoplegia (PEO). The authors report on a patient
      homozygous for a recessive missense mutation in POLG who presented with a
      multisystem disorder without PEO. The most prominent features were myoclonus,
      seizure, and sensory ataxic neuropathy, so the clinical picture overlapped with
      the syndrome of myoclonus, epilepsy, and ragged red fibers (MERRF).

PMID- 14694058
TI  - Chronic neuropathy with IgM anti-ganglioside antibodies: lack of long term
      response to rituximab.
AB  - Two patients with chronic motor neuropathy, high antiganglioside antibody (AGA)
      titers, and a declining response to IV immunoglobulins were treated with
      rituximab at a standard dose. The drug was well tolerated and effectively
      eliminated peripheral B cells (CD20+), but AGA titers continued significantly
      high. No clinical improvement was detected during the 1-year follow-up.

PMID- 14694059
TI  - Is there less micrographia in foreign language in Parkinson's disease?

PMID- 14694060
TI  - Leukoencephalopathy with vanishing white matter:: an adult onset case.

PMID- 14694061
TI  - Persistent antiepileptic effects after vagus nerve stimulation ends?

PMID- 14694062
TI  - Hereditary elevation of angiotensin converting enzyme suggesting
      neurosarcoidosis.

PMID- 14694064
TI  - MR diffusion-weighted imaging in a case of West Nile virus encephalitis.

PMID- 14694063
TI  - Peripheral nerve disease in SARS:: report of a case.

PMID- 14694065
TI  - Fiction: lemon, with a twist.

PMID- 14694066
TI  - Prognosis in amyotrophic lateral sclerosis: a population-based study.

PMID- 14694067
TI  - Acute migraine treatment with droperidol.

PMID- 14694068
TI  - Neurophysiologic analysis of neuromuscular symptoms in UK Gulf War veterans.

PMID- 14694071
TI  - Patient page. The diagnosis of epilepsy and the art of listening.

PMID- 14694072
TI  - Concerted and nonconcerted evolution of the Hsp70 gene superfamily in two sibling
      species of nematodes.
AB  - We have identified the Hsp70 gene superfamily of the nematode Caenorhabditis
      briggsae and investigated the evolution of these genes in comparison with Hsp70
      genes from C. elegans, Drosophila, and yeast. The Hsp70 genes are classified into
      three monophyletic groups according to their subcellular localization, namely,
      cytoplasm (CYT), endoplasmic reticulum (ER), and mitochondria (MT). The Hsp110
      genes can be classified into the polyphyletic CYT group and the monophyletic ER
      group. The different Hsp70 and Hsp110 groups appeared to evolve following the
      model of divergent evolution. This model can also explain the evolution of the ER
      and MT genes. On the other hand, the CYT genes are divided into heat-inducible
      and constitutively expressed genes. The constitutively expressed genes have
      evolved more or less following the birth-and-death process, and the rates of gene
      birth and gene death are different between the two nematode species. By contrast,
      some heat-inducible genes show an intraspecies phylogenetic clustering. This
      suggests that they are subject to sequence homogenization resulting from gene
      conversion-like events. In addition, the heat-inducible genes show high levels of
      sequence conservation in both intra-species and inter-species comparisons, and in
      most cases, amino acid sequence similarity is higher than nucleotide sequence
      similarity. This indicates that purifying selection also plays an important role
      in maintaining high sequence similarity among paralogous Hsp70 genes. Therefore,
      we suggest that the CYT heat-inducible genes have been subjected to a combination
      of purifying selection, birth-and-death process, and gene conversion-like events.

PMID- 14694073
TI  - Evolution of Cryptosporidium parvum lactate dehydrogenase from malate
      dehydrogenase by a very recent event of gene duplication.
AB  - We have expressed the L-lactate dehydrogenase (LDH) and L-malate dehydrogenase
      (malDH) genes from the apicomplexan Cryptosporidium parvum (CpLDH1 and CpMalDH1)
      as maltose-binding protein (MBP) fusion proteins in Escherichia coli. The
      substrate specificities, enzymatic kinetics, and oligomeric states of these two
      parasite enzymes have been characterized. By taking advantage of recently
      completed and ongoing apicomplexan genome sequencing projects, we identified
      additional MalDH genes from Plasmodium spp., Toxoplasma gondii, and Eimeria
      tenella that were previously unavailable. All apicomplexan MalDHs appeared to be
      cytosolic and no organellar homologs were identified from the completely
      sequenced P. falciparum genome and other ongoing apicomplexan genome-sequencing
      projects. Using these expanded apicomplexan LDH and MalDH sequence databases, we
      reexamined their phylogenetic relationships and reconfirmed their relationship to
      alpha-proteobacterial MalDHs. All LDH and MalDH enzymes from apicomplexans were
      monophyletic within the LDH-like MalDH group (i.e., MalDH resembling LDH) as a
      sister to alpha-proteobacterial MalDHs. All apicomplexan LDHs, with the exception
      of CpLDH1, formed a separate clade from their MalDH counterparts, indicating that
      these LDHs were evolved from an ancestral apicomplexan MalDH by a gene
      duplication coupled with functional conversion before the expansion of
      apicomplexans. Finally, CpLDH1 was consistently placed together with CpMalDH1
      within the apicomplexan MalDH cluster, confirming an early working hypothesis
      that CpLDH1 was probably evolved from the same ancestor of CpMalDH1 by a very
      recent gene duplication that occurred after C. parvum diverged from other
      apicomplexans.

PMID- 14694074
TI  - A "Long Indel" model for evolutionary sequence alignment.
AB  - We present a new probabilistic model of sequence evolution, allowing indels of
      arbitrary length, and give sequence alignment algorithms for our model.
      Previously implemented evolutionary models have allowed (at most) single-residue
      indels or have introduced artifacts such as the existence of indivisible
      "fragments." We compare our algorithm to these previous methods by applying it to
      the structural homology dataset HOMSTRAD, evaluating the accuracy of (1)
      alignments and (2) evolutionary time estimates. With our method, it is possible
      (for the first time) to integrate probabilistic sequence alignment, with
      reliability indicators and arbitrary gap penalties, in the same framework as
      phylogenetic reconstruction. Our alignment algorithm requires that we evaluate
      the likelihood of any specific path of mutation events in a continuous-time
      Markov model, with the event times integrated out. To this effect, we introduce a
      "trajectory likelihood" algorithm (Appendix A). We anticipate that this algorithm
      will be useful in more general contexts, such as Markov Chain Monte Carlo
      simulations.

PMID- 14694075
TI  - Evolution of the APETALA3 and PISTILLATA lineages of MADS-box-containing genes in
      the basal angiosperms.
AB  - The B class genes, including homologs of the Arabidopsis loci APETALA3 (AP3) and
      PISTILLATA (PI ), appear to play a conserved role in the determination of petal
      and stamen identity across core eudicot angiosperms. Understanding how and when
      these functions evolved is a critical component of elucidating the evolution of
      flowers, particularly the appearance of petaloid perianth organs. Before
      comparisons of gene expression patterns or functions can be made, however, it is
      necessary to establish the orthology of AP3 and PI homologs from basal
      angiosperms. Here, we report the identification and analysis of 29 new
      representatives of the B gene lineage from basal ANITA and magnoliid dicot
      angiosperms. These studies indicate that gene duplications have occurred at every
      phylogenetic level, both before and after the duplication that produced the
      separate AP3 and PI lineages. Comparison of genomic structure among PI homologs
      indicates that a 12-nucleotide deletion that had been considered synapomorphic
      for the whole PI lineage actually arose within the ANITA grade, after the split
      of the Nymphaeales but before the separation of the Austrobaileyales. Evidence
      for alternative splicing of the Nymphaea AP3 homolog is also presented. The
      implications of these findings for angiosperm systematics, the conservation of
      AP3 and PI gene function, and the evolution of the ABC program are discussed.

PMID- 14694076
TI  - The ingi and RIME non-LTR retrotransposons are not randomly distributed in the
      genome of Trypanosoma brucei.
AB  - The ingi (long and autonomous) and RIME (short and nonautonomous) non--long
      terminal repeat retrotransposons are the most abundant mobile elements
      characterized to date in the genome of the African trypanosome Trypanosoma
      brucei. These retrotransposons were thought to be randomly distributed, but a
      detailed and comprehensive analysis of their genomic distribution had not been
      performed until now. To address this question, we analyzed the ingi/RIME
      sequences and flanking sequences from the ongoing T. brucei genome sequencing
      project (TREU927/4 strain). Among the 81 ingi/RIME elements analyzed, 60% are
      complete, and 7% of the ingi elements (approximately 15 copies per haploid
      genome) appear to encode for their own transposition. The size of the direct
      repeat flanking the ingi/RIME retrotransposons is conserved (i.e., 12-bp), and a
      strong 11-bp consensus pattern precedes the 5'-direct repeat. The presence of a
      consensus pattern upstream of the retroelements was confirmed by the analysis of
      the base occurrence in 294 GSS containing 5'-adjacent ingi/RIME sequences. The
      conserved sequence is present upstream of ingis and RIMEs, suggesting that ingi
      encoded enzymatic activities are used for retrotransposition of RIMEs, which are
      short nonautonomous retroelements. In conclusion, the ingi and RIME retroelements
      are not randomly distributed in the genome of T. brucei and are preceded by a
      conserved sequence, which may be the recognition site of the ingi-encoded
      endonuclease.

PMID- 14694077
TI  - Phylogenetic dating and characterization of gene duplications in vertebrates: the
      cartilaginous fish reference.
AB  - Vertebrates originated in the lower Cambrian. Their diversification and
      morphological innovations have been attributed to large-scale gene or genome
      duplications at the origin of the group. These duplications are predicted to have
      occurred in two rounds, the "2R" hypothesis, or they may have occurred in one
      genome duplication plus many segmental duplications, although these hypotheses
      are disputed. Under such models, most genes that are duplicated in all
      vertebrates should have originated during the same period. Previous work has
      shown that indeed duplications started after the speciation between vertebrates
      and the closest invertebrate, amphioxus, but have not set a clear ending.
      Consideration of chordate phylogeny immediately shows the key position of
      cartilaginous vertebrates (Chondrichthyes) to answer this question. Did gene
      duplications occur as frequently during the 45 Myr between the cartilaginous/bony
      vertebrate split and the fish/tetrapode split as in the previous approximately
      100 Myr? Although the time interval is relatively short, it is crucial to
      understanding the events at the origin of vertebrates. By a systematic appraisal
      of gene phylogenies, we show that significantly more duplications occurred before
      than after the cartilaginous/bony vertebrate split. Our results support rounds of
      gene or genome duplications during a limited period of early vertebrate evolution
      and allow a better characterization of these events.

PMID- 14694078
TI  - The natural history of nitrogen fixation.
AB  - In recent years, our understanding of biological nitrogen fixation has been
      bolstered by a diverse array of scientific techniques. Still, the origin and
      extant distribution of nitrogen fixation has been perplexing from a phylogenetic
      perspective, largely because of factors that confound molecular phylogeny such as
      sequence divergence, paralogy, and horizontal gene transfer. Here, we make use of
      110 publicly available complete genome sequences to understand how the core
      components of nitrogenase, including NifH, NifD, NifK, NifE, and NifN proteins,
      have evolved. These genes are universal in nitrogen fixing organisms-typically
      found within highly conserved operons-and, overall, have remarkably congruent
      phylogenetic histories. Additional clues to the early origins of this system are
      available from two distinct clades of nitrogenase paralogs: a group composed of
      genes essential to photosynthetic pigment biosynthesis and a group of
      uncharacterized genes present in methanogens and in some photosynthetic bacteria.
      We explore the complex genetic history of the nitrogenase family, which is
      replete with gene duplication, recruitment, fusion, and horizontal gene transfer
      and discuss these events in light of the hypothesized presence of nitrogenase in
      the last common ancestor of modern organisms, as well as the additional
      possibility that nitrogen fixation might have evolved later, perhaps in
      methanogenic archaea, and was subsequently transferred into the bacterial domain.

PMID- 14694079
TI  - Dramatic diversity of ciliate histone H4 genes revealed by comparisons of
      patterns of substitutions and paralog divergences among eukaryotes.
AB  - The accumulation of divergent histone H4 amino acid sequences within and between
      ciliate lineages challenges traditional views of the evolution of this essential
      eukaryotic protein. We analyzed histone H4 sequences from 13 species of ciliates
      and compared these data with sequences from well-sampled eukaryotic clades.
      Ciliate histone H4s differ from one another at as many as 46% of their amino
      acids, in contrast with the highly conserved character of this protein in most
      other eukaryotes. Equally striking, we find paralogs of histone H4 within ciliate
      genomes that differ by up to 25% of their amino acids, whereas paralogs in other
      eukaryotes share identical or nearly identical amino acid sequences. Moreover,
      the most divergent H4 proteins within ciliates are found in the lineages with
      highly processed macronuclear genomes. Our analyses demonstrate that the dual
      nature of ciliate genomes-the presence of a "germline" micronucleus and a
      "somatic" macronucleus within each cell-allowed the dramatic variation in ciliate
      histone genes by altering functional constraints or enabling adaptive evolution
      of the histone H4 protein, or both.

PMID- 14694080
TI  - Theoretical foundation of the balanced minimum evolution method of phylogenetic
      inference and its relationship to weighted least-squares tree fitting.
AB  - Due to its speed, the distance approach remains the best hope for building
      phylogenies on very large sets of taxa. Recently (R. Desper and O. Gascuel, J.
      Comp. Biol. 9:687-705, 2002), we introduced a new "balanced" minimum evolution
      (BME) principle, based on a branch length estimation scheme of Y. Pauplin (J.
      Mol. Evol. 51:41-47, 2000). Initial simulations suggested that FASTME, our
      program implementing the BME principle, was more accurate than or equivalent to
      all other distance methods we tested, with running time significantly faster than
      Neighbor-Joining (NJ). This article further explores the properties of the BME
      principle, and it explains and illustrates its impressive topological accuracy.
      We prove that the BME principle is a special case of the weighted least-squares
      approach, with biologically meaningful variances of the distance estimates. We
      show that the BME principle is statistically consistent. We demonstrate that
      FASTME only produces trees with positive branch lengths, a feature that separates
      this approach from NJ (and related methods) that may produce trees with branches
      with biologically meaningless negative lengths. Finally, we consider a large
      simulated data set, with 5,000 100-taxon trees generated by the Aldous beta
      splitting distribution encompassing a range of distributions from Yule-Harding to
      uniform, and using a covarion-like model of sequence evolution. FASTME produces
      trees faster than NJ, and much faster than WEIGHBOR and the weighted least
      squares implementation of PAUP*. Moreover, FASTME trees are consistently more
      accurate at all settings, ranging from Yule-Harding to uniform distributions, and
      all ranges of maximum pairwise divergence and departure from molecular clock.
      Interestingly, the covarion parameter has little effect on the tree quality for
      any of the algorithms. FASTME is freely available on the web.

PMID- 14694081
TI  - The melanocortin system in Fugu: determination of POMC/AGRP/MCR gene repertoire
      and synteny, as well as pharmacology and anatomical distribution of the MCRs.
AB  - The G-protein-coupled melanocortin receptors (MCRs) play an important role in a
      variety of essential functions such as the regulation of pigmentation, energy
      homeostasis, and steroid production. We performed a comprehensive
      characterization of the MC system in Fugu (Takifugu rubripes). We show that Fugu
      has an AGRP gene with high degree of conservation in the C-terminal region in
      addition to a POMC gene lacking gamma-MSH. The Fugu genome contains single copies
      of four MCRs, whereas the MC3R is missing. The MC2R and MC5R are found in tandem
      and remarkably contain one and two introns, respectively. We suggest that these
      introns were inserted through a reverse splicing mechanism into the DRY motif
      that is widely conserved through GPCRs. We were able to assemble large blocks
      around the MCRs in Fugu, showing remarkable synteny with human chromosomes 16 and
      18. Detailed pharmacological characterization showed that ACTH had surprisingly
      high affinity for the Fugu MC1R and MC4R, whereas alpha-MSH had lower affinity.
      We also showed that the MC2R gene in Fugu codes for an ACTH receptor, which did
      not respond to alpha-MSH. All the Fugu receptors were able to couple functionally
      to cAMP production in line with the mammalian orthologs. The anatomical
      characterization shows that the MC2R is expressed in the brain in addition to the
      head-kidney, whereas the MC4R and MC5R are found in both brain regions and
      peripheral tissues. This is the first comprehensive genomic and functional
      characterization of a GPCR family within the Fugu genome. The study shows that
      some parts of the MC system are highly conserved through vertebrate evolution,
      such as regions in POMC coding for ACTH, alpha-MSH, and beta-MSH, the C-terminal
      region of AGRP, key binding units within the MC1R, MC2R, MC4R, and MC5R, synteny
      blocks around the MCRs, pharmacological properties of the MC2R, whereas other
      parts in the system are either missing, such as the MC3R and gamma-MSH, or
      different as compared to mammals, such as the affinity of ACTH and MSH peptides
      to MC1R and MC4R and the anatomical expression pattern of the MCRs.

PMID- 14694082
TI  - Deletion bias in avian introns over evolutionary timescales.
AB  - The role that introns play in the function and evolution of nuclear genomes is
      not fully understood. Recent models of intron evolution suggest that selection
      and drift may interact to maintain introns in multicellular organisms. In
      addition, deletion mutations are more likely to become fixed than insertion
      mutations. Examination of indel substitutions over macroevolutionary timescales
      in pigeons and doves (Aves: Columbiformes) reveals that deletion substitutions
      outnumber insertion substitutions by over six times. The length of indel events
      is variable.

PMID- 14694083
TI  - The basolateral sorting signals of the thyrotropin and luteinizing hormone
      receptors: an unusual family of signals sharing an unusual distal intracellular
      localization, but unrelated in their structures.
AB  - The mechanisms of the basolateral targeting of G protein-coupled receptors remain
      largely unknown. Mutagenesis experiments have allowed us to identify the
      basolateral sorting signals of the TSH and LH receptors expressed in Madin-Darby
      canine kidney cells and thyroid follicular FRT cells. Unexpectedly these signals
      (amino acids 731-746 and 672-689, respectively) share an unusual localization in
      the distal part of the intracellular domain of the receptors at a marked distance
      from the membrane. When grafted onto the p75-neurotropin receptor, these signals
      redirect this normally apically expressed protein to the basolateral cell
      surface. They are independent of the endocytosis signal. The basolateral sorting
      signals of TSH, LH, and FSH receptors do not exhibit primary sequence homology
      with each other or with any other known signal. Furthermore, circular dichroism
      studies show that the three signals exhibit distinct secondary structures. The
      TSH receptor has a stable helical structure, the LH receptor has both helix and
      beta-sheet structures, and the FSH receptor sorting signal has a main random coil
      structure. This means that even in closely-related receptors different secondary
      structures can be found for basolateral signals unrelated to internalization
      signals. This observation contrasts with what is known about basolateral signals
      related to internalization signals for which a common beta-turn structure has
      been described. Deletion of the basolateral sorting signals results in apical
      targeting of the receptors, suggesting the existence of apical sorting
      information. However, a soluble form of the TSH receptor, which harbors all N-
      and putative O-linked oligosaccharides, is secreted in a nonpolarized fashion.
      This implies that apical sorting information must be located elsewhere, either in
      the transmembrane or in the intracellular domains of the receptor.

PMID- 14694084
TI  - Sweet changes: glucose homeostasis can be altered by manipulating genes
      controlling hepatic glucose metabolism.
AB  - The liver is responsible for glucose synthesis in the fasting state, and glucose
      uptake, storage, and utilization in the fed state. A phenotypic switch, normally
      initiated by insulin or glucagon, controls the transition between the two states,
      which includes transcriptional alterations that regulate metabolic enzyme
      abundance for multiple metabolic pathways in a coordinated manner. A network of
      transcription factors, coactivators, and corepressors direct these changes, thus
      acting as transcriptional sensors of the nutritional status of an organism. The
      inability of the hepatocyte to undergo this metabolic reprogramming is
      characteristic of diabetes mellitus. Modulations that control the amount of
      individual metabolic enzymes or transcription factors can initiate the fasting-to
      fed transition of the hepatocyte in an insulin-independent manner. Alternatively,
      overexpression of key regulators of metabolism can lock hepatocytes in the fasted
      state. These manipulations alter hepatic glucose flux, leading to either
      amelioration or induction of diabetes mellitus. These maneuvers reveal the
      complexity of the coordinated mechanisms used by the liver to alter its phenotype
      and provide evidence for the control strength of metabolic signaling.

PMID- 14694085
TI  - Activation of adenosine triphosphate-sensitive potassium channels by acyl
      coenzyme A esters involves multiple phosphatidylinositol 4,5-bisphosphate
      interacting residues.
AB  - ATP-sensitive potassium (K(ATP)) channels are crucial to pancreatic endocrine
      function and their activation by acyl coenzyme A esters (acyl CoAs) may disrupt
      hormone secretion, contributing to the pathophysiology of type 2 diabetes. The
      molecular mechanism of this activation is potentially important in our further
      understanding of this disease. We use excised patch-clamp techniques to assess
      the effects of N- and C-terminal Kir6.2 mutations on the activation of
      recombinant K(ATP) channels by palmitoyl CoA. We demonstrate that several
      residues previously shown to be involved in channel activation by the
      structurally related lipid phosphatidylinositol 4,5-bisphosphate (PIP(2)) also
      play a role in activation by acyl CoAs, including R54, R176, R192, and R301.
      Mutation of these residues caused decreased open probability in the absence of
      ATP and slower and greater relative activation by both PIP(2) and acyl CoAs. By
      contrast, K185Q, which probably alters ATP binding, had no effect on either
      PIP(2) or palmitoyl CoA activation. These findings suggest that activation by the
      two classes of lipids involves multiple common residues. We use the crystal
      structure of a related channel, KirBac1.1, as a template to locate the residues
      of interest in this study within a putative three-dimensional model of Kir6.2. We
      propose a model in which these residues mediate both direct electrostatic
      interactions and allosteric modulations of open state stability.

PMID- 14694086
TI  - Important role for the CA-NC spacer region in the assembly of bovine
      immunodeficiency virus Gag protein.
AB  - Lentiviral Gag proteins contain a short spacer sequence that separates the capsid
      (CA) from the downstream nucleocapsid (NC) domain. This short spacer has been
      shown to play an important role in the assembly of human immunodeficiency virus
      type 1 (HIV-1). We have now extended this finding to the CA-NC spacer motif
      within the Gag protein of bovine immunodeficiency virus (BIV). Mutation of this
      latter spacer sequence led to dramatic reductions in virus production, which was
      mainly attributed to the severely disrupted association of the mutated Gag with
      the plasma membrane, as shown by the results of membrane flotation assays and
      confocal microscopy. Detailed mutagenesis analysis of the BIV CA-NC spacer region
      for virus assembly determinants led to the identification of two key residues,
      L368 and M372, which are separated by three amino acids, 369-VAA-371.
      Incidentally, the same two residues are present within the HIV-1 CA-NC spacer
      region at positions 364 and 368 and have also been shown to be crucial for HIV-1
      assembly. Regardless of this conservation between these two viruses, the BIV CA
      NC spacer could not be replaced by its HIV-1 counterpart without decreasing virus
      production, as opposed to its successful replacement by the CA-NC spacer
      sequences from the nonprimate lentiviruses such as feline immunodeficiency virus
      (FIV), equine infectious anemia virus and visna virus, with the sequence from FIV
      showing the highest effectiveness in this regard. Taken together, these data
      suggest a pivotal role for the CA-NC spacer region in the assembly of BIV Gag;
      however, the mechanism involved therein may differ from that for the HIV-1 CA-NC
      spacer.

PMID- 14694087
TI  - Impacts of epitope expression kinetics and class I downregulation on the
      antiviral activity of human immunodeficiency virus type 1-specific cytotoxic T
      lymphocytes.
AB  - The determinants of CD8(+) cytotoxic T-lymphocyte (CTL) antiviral activity
      against human immunodeficiency virus type 1 (HIV-1) remain poorly defined.
      Although recent technological advances have markedly enhanced the ability to
      detect HIV-1-specific T cells, commonly used assays do not reveal their direct
      interaction with virus. We investigated two determinants of CTL antiviral
      efficiency by manipulating HIV-1 and measuring the effects on CTL suppression of
      viral replication in acutely infected cells. Translocation of a Gag epitope into
      the early protein Nef markedly increased the activity of CTL recognizing that
      epitope, in comparison to HIV-1 expressing the epitope normally in the late
      protein Gag. Because this epitope translocation resulted not only in earlier
      expression but also in loss of major histocompatibility complex class I
      downregulation by Nef, the activities of CTL against a panel of viral constructs
      differing in kinetics of epitope expression and class I downmodulation were
      compared. The results indicated that both the timing of epitope expression and
      the reduction of class I have profound effects on the ability of CTL to suppress
      HIV-1 replication in acutely infected cells. The epitope targeting of CTL and
      viral control of class I therefore likely play important roles in the ability of
      CTL to exert pressure on HIV-1.

PMID- 14694088
TI  - Inhibition of human immunodeficiency virus type 1 entry in cells expressing gp41
      derived peptides.
AB  - As the limitations of antiretroviral drug therapy, such as toxicity and
      resistance, become evident, interest in alternative therapeutic approaches for
      human immunodeficiency virus (HIV) infection is growing. We developed the first
      gene therapeutic strategy targeting entry of a broad range of HIV type 1 (HIV-1)
      variants. Infection was inhibited at the level of membrane fusion by retroviral
      expression of a membrane-anchored peptide derived from the second heptad repeat
      of the HIV-1 gp41 transmembrane glycoprotein. To achieve maximal expression and
      antiviral activity, the peptide itself, the scaffold for presentation of the
      peptide on the cell surface, and the retroviral vector backbone were optimized.
      This optimized construct effectively inhibited virus replication in cell lines
      and primary blood lymphocytes. The membrane-anchored C-peptide was also shown to
      bind to free gp41 N peptides, suggesting that membrane-anchored antiviral C
      peptides have a mode of action similar to that of free gp41 C peptides.
      Preclinical toxicity and efficacy studies of this antiviral vector have been
      completed, and clinical trials are in preparation.

PMID- 14694089
TI  - Toll-like receptor 4-dependent activation of dendritic cells by a retrovirus.
AB  - Mouse mammary tumor virus (MMTV) is a milk-borne retrovirus that exploits the
      adaptive immune system. It has recently been shown that MMTV activates B cells
      via Toll-like receptor 4 (TLR4), a molecule involved in innate immune responses.
      Here, we show that direct virus binding to TLR4 induced maturation of bone marrow
      derived dendritic cells and up-regulated expression of the MMTV entry receptor
      (CD71) on these cells. In vivo, MMTV increased the number of dendritic cells in
      neonatal Peyer's patches and their expression of CD71; both these effects were
      dependent on TLR4. Thus, retroviral signaling through TLRs plays a critical role
      in dendritic-cell participation during infection.

PMID- 14694090
TI  - CXC chemokine ligand 10 controls viral infection in the central nervous system:
      evidence for a role in innate immune response through recruitment and activation
      of natural killer cells.
AB  - How chemokines shape the immune response to viral infection of the central
      nervous system (CNS) has largely been considered within the context of
      recruitment and activation of antigen-specific lymphocytes. However, chemokines
      are expressed early following viral infection, suggesting an important role in
      coordinating innate immune responses. Herein, we evaluated the contributions of
      CXC chemokine ligand 10 (CXCL10) in promoting innate defense mechanisms following
      coronavirus infection of the CNS. Intracerebral infection of RAG1(-/-) mice with
      a recombinant CXCL10-expressing murine coronavirus (mouse hepatitis virus)
      resulted in protection from disease and increased survival that correlated with a
      significant increase in recruitment and activation of natural killer (NK) cells
      within the CNS. Accumulation of NK cells resulted in a reduction in viral titers
      that was dependent on gamma interferon secretion. These results indicate that
      CXCL10 expression plays a pivotal role in defense following coronavirus infection
      of the CNS by enhancing innate immune responses.

PMID- 14694091
TI  - Identification of an extracellular domain within the human PiT2 receptor that is
      required for amphotropic murine leukemia virus binding.
AB  - Human PiT2 (PiT2) is a multiple-membrane-spanning protein that functions as a
      type III sodium phosphate cotransporter and as the receptor for amphotropic
      murine leukemia virus (A-MuLV). Human PiT1 (PiT1), another type III sodium
      phosphate cotransporter, is a highly related protein that functions as a receptor
      for gibbon ape leukemia virus but not for A-MuLV. The ability of PiT1 and PiT2 to
      function as discrete viral receptors with unique properties presumably is
      reflected in critical residue differences between these two proteins. Early
      efforts to map the region(s) within PiT2 that is important for virus binding
      and/or entry relied on infection results obtained with PiT1-PiT2 chimeric cDNAs
      expressed in Chinese hamster ovary (CHOK1) cells. These attempts to localize the
      PiT2 virus-binding site were hampered because they were based on infectivity, not
      binding, assays, and therefore, receptors that bound but failed to facilitate
      virus entry could not be distinguished from receptors that did not bind virus.
      Using a more accurate topological model for PiT2 as well as an A-MuLV receptor
      binding assay, we have identified extracellular domain one (ECD1) of the human
      PiT2 receptor as being important for A-MuLV binding and infection.

PMID- 14694092
TI  - Competitive fitness of nevirapine-resistant human immunodeficiency virus type 1
      mutants.
AB  - Determining the fitness of drug-resistant human immunodeficiency virus type 1
      (HIV-1) strains is necessary for the development of population-based studies of
      resistance patterns. For this purpose, we have developed a reproducible,
      systematic assay to determine the competitive fitness of HIV-1 drug-resistant
      mutants. To demonstrate the applicability of this assay, we tested the fitness of
      the five most common nevirapine-resistant mutants (103N, 106A, 181C, 188C, and
      190A), with mutations in HIV-1 reverse transcriptase (RT), singly and in
      combination (for a total of 31 variants) in a defined HIV-1 background. For these
      experiments, the 27 RT variants that produced viable virus were cocultured with
      wild-type virus without nevirapine. The ratios of the viral species were
      determined over time by utilization of a quantitative real-time RT-PCR-based
      assay. These experiments revealed that all of the viable variants were less fit
      than the wild type and demonstrated that the order of relative fitness of the
      single mutants tested was as follows: 103N > 181C > 190A > 188C > 106A. This
      order correlated with the commonality of these mutants as a result of nevirapine
      monotherapy. These investigations also revealed that, on average, the double
      mutants were less fit than the single mutants and the triple mutants were less
      fit than the double mutants. However, the fitness of the single and double
      mutants was often not predictive of the fitness of the derivative triple mutants,
      suggesting the presence of complex interactions between the closely aligned
      residues that confer nevirapine resistance. This complexity was also evident from
      the observation that all three of the replication-competent quadruple mutants
      were fitter than most of the triple mutants, and in some cases, even the double
      mutants. Our data suggest that, in many cases, viral fitness is the determining
      factor in the evolution of nevirapine-resistant mutants in vivo, that
      interactions between the residues that confer nevirapine resistance are complex,
      and that these interactions substantially affect reverse transcriptase structure
      and/or function.

PMID- 14694093
TI  - Genetic and biochemical analysis of cis regulatory elements within the
      keratinocyte enhancer region of the human papillomavirus type 31 upstream
      regulatory region during different stages of the viral life cycle.
AB  - Using linker scanning mutational analysis, we recently identified potential cis
      regulatory elements contained within the 5' upstream regulatory region (URR)
      domain and auxiliary enhancer (AE) region of the human papillomavirus type 31
      (HPV31) URR involved in the regulation of E6/E7 promoter activity at different
      stages of the viral life cycle. For the present study, we extended the linker
      scanning mutational analysis to identify potential cis elements located in the
      keratinocyte enhancer (KE) region (nucleotides 7511 to 7762) of the HPV31 URR and
      to characterize cellular factors that bind to these elements under conditions
      representing different stages of the viral life cycle. The linker scanning
      mutational analysis identified viral cis elements located in the KE region that
      regulate transcription in the presence and absence of any viral gene products or
      viral DNA replication and determine the role of host tissue differentiation on
      viral transcriptional regulation. Using electrophoretic mobility shift assays, we
      illustrated defined reorganization in the composition of cellular transcription
      factors binding to the same cis regulatory elements at different stages of the
      HPV differentiation-dependent life cycle. Our studies provide an extensive map of
      functional elements in the KE region of the HPV31 URR, identify cis regulatory
      elements that exhibit significant transcription regulatory potential, and
      illustrate changes in specific protein-DNA interactions at different stages of
      the viral life cycle. The variable recruitment of transcription factors to the
      same cis element under different cellular conditions may represent a mechanism
      underlying the tight link between keratinocyte differentiation and E6/E7
      expression.

PMID- 14694094
TI  - Persistent recognition of autologous virus by high-avidity CD8 T cells in
      chronic, progressive human immunodeficiency virus type 1 infection.
AB  - CD8 T-cell responses are thought to be crucial for control of viremia in human
      immunodeficiency virus (HIV) infection but ultimately fail to control viremia in
      most infected persons. Studies in acute infection have demonstrated strong CD8
      mediated selection pressure and evolution of mutations conferring escape from
      recognition, but the ability of CD8 T-cell responses that persist in late-stage
      infection to recognize viruses present in vivo has not been determined.
      Therefore, we studied 24 subjects with advanced HIV disease (median viral load =
      142,000 copies/ml; median CD4 count = 71/ micro l) and determined HIV-1-specific
      CD8 T-cell responses to all expressed viral proteins using overlapping peptides
      by gamma interferon Elispot assay. Chronic-stage virus was sequenced to evaluate
      autologous sequences within Gag epitopes, and functional avidity of detected
      responses was determined. In these subjects, the median number of epitopic
      regions targeted was 13 (range, 2 to 39) and the median cumulative magnitude of
      CD8 T-cell responses was 5,760 spot-forming cells/10(6) peripheral blood
      mononuclear cells (range, 185 to 24,700). On average six (range, one to 8)
      proteins were targeted. For 89% of evaluated CD8 T-cell responses, the autologous
      viral sequence was predicted to be well recognized by these responses and the
      majority of analyzed optimal epitopes were recognized with medium to high
      functional avidity by the contemporary CD8 T cells. Withdrawal of antigen by
      highly active antiretroviral therapy led to a significant decline both in breadth
      (P = 0.032) and magnitude (P = 0.0098) of these CD8 T-cell responses, providing
      further evidence that these responses had been driven by recognition of
      autologous virus. These results indicate that strong, broadly directed, and high
      avidity gamma-interferon-positive CD8 T-cells directed at autologous virus
      persist in late disease stages, and the absence of mutations within viral
      epitopes indicates a lack of strong selection pressure mediated by these
      responses. These data imply functional impairment of CD8 T-cell responses in late
      stage infection that may not be reflected by gamma interferon-based screening
      techniques.

PMID- 14694095
TI  - cis-Acting sequences that contribute to the synthesis of relaxed-circular DNA of
      human hepatitis B virus.
AB  - Synthesis of the relaxed-circular (RC) genome of hepadnaviruses is a multistep
      process that requires template switching during reverse transcription. Studies of
      duck hepatitis B virus indicated the presence of cis-acting sequences, distinct
      from the donor and acceptor sequences for the template switches, which contribute
      to the synthesis of RC DNA. However, knowledge about cis-acting requirements
      distinct from the donor and acceptor sites for human hepatitis B virus (HBV) was
      lacking. In this study, we searched for cis-acting sequences for synthesis of HBV
      RC DNA by analyzing a set of deletion variants that collectively represent most
      of the HBV genome. Sequences of epsilon, DR1, DR2, 5'r, and 3'r were not analyzed
      in the study. Results from Southern blotting showed that multiple cis-acting
      sequences were involved in the synthesis of HBV RC DNA. Analysis of several
      HBV/woodchuck hepatitis virus chimeras corroborated the findings from the
      analysis of deletion variants. This study represents a comprehensive and
      quantitative analysis of cis-acting sequences that contribute to the synthesis of
      HBV RC DNA.

PMID- 14694096
TI  - A point mutation within conserved region VI of herpes simplex virus type 1 DNA
      polymerase confers altered drug sensitivity and enhances replication fidelity.
AB  - Herpes simplex virus type 1 (HSV-1) DNA polymerase contains several conserved
      regions within the polymerase domain. The conserved regions I, II, III, V, and
      VII have been shown to have functional roles in the interaction with
      deoxynucleoside triphosphates (dNTPs) and DNA. However, the role of conserved
      region VI in DNA replication has remained unclear due, in part, to the lack of a
      well-characterized region VI mutant. In this report, recombinant viruses
      containing a point mutation (L774F) within the conserved region VI were
      constructed. These recombinant viruses were more susceptible to aphidicolin and
      resistant to both foscarnet and acyclovir, compared to the wild-type KOS strain.
      Marker transfer experiments demonstrated that the L774F mutation conferred the
      altered drug sensitivities. Furthermore, mutagenesis assays demonstrated that
      L774F recombinant viruses containing the supF marker gene, which was integrated
      within the thymidine kinase locus (tk), exhibited increased fidelity of DNA
      replication. These data indicate that conserved region VI, together with other
      conserved regions, forms the polymerase active site, has a role in the
      interaction with deoxyribonucleotides, and regulates DNA replication fidelity.
      The possible effect of the L774F mutation in altering the polymerase structure
      and activity is discussed.

PMID- 14694097
TI  - Simian virus 40-based replication of catalytically inactive human
      immunodeficiency virus type 1 integrase mutants in nonpermissive T cells and
      monocyte-derived macrophages.
AB  - Integrase function is required for retroviral replication in most instances.
      Although certain permissive T-cell lines support human immunodeficiency virus
      type 1 (HIV-1) replication in the absence of functional integrase, most cell
      lines and primary human cells are nonpermissive for integrase mutant growth.
      Since unintegrated retroviral DNA is lost from cells following cell division, we
      investigated whether incorporating a functional origin of DNA replication into
      integrase mutant HIV-1 might overcome the block to efficient gene expression and
      replication in nonpermissive T-cell lines and primary cells. Whereas the Epstein
      Barr virus (EBV) origin (oriP) did little to augment expression from an integrase
      mutant reporter virus in EBV nuclear antigen 1-expressing cells, simian virus 40
      (SV40) oriT dramatically enhanced integrase mutant infectivity in T-antigen (Tag)
      expressing cells. Incorporating oriT into the nef position of a full-length,
      integrase-defective virus strain yielded efficient replication in Tag-expressing
      nonpermissive Jurkat T cells without reversion to an integration-competent
      genotype. Adding Tag to integrase mutant-oriT viruses yielded 11.3-kb SV40-HIV
      chimeras that replicated in Jurkat cells and primary monocyte-derived
      macrophages. Real-time quantitative PCR analyses of Jurkat cell infections
      revealed that amplified copies of unintegrated DNA likely contributed to SV40-HIV
      integrase mutant replication. SV40-based HIV-1 integrase mutant replication in
      otherwise nonpermissive cells suggests alternative approaches to standard
      integrase-mediated retroviral gene transfer strategies.

PMID- 14694098
TI  - Characterization of the RNA components of a putative molecular switch in the 3'
      untranslated region of the murine coronavirus genome.
AB  - RNA virus genomes contain cis-acting sequence and structural elements that
      participate in viral replication. We previously identified a bulged stem-loop
      secondary structure at the upstream end of the 3' untranslated region (3' UTR) of
      the genome of the coronavirus mouse hepatitis virus (MHV). This element,
      beginning immediately downstream of the nucleocapsid gene stop codon, was shown
      to be essential for virus replication. Other investigators discovered an adjacent
      downstream pseudoknot in the 3' UTR of the closely related bovine coronavirus
      (BCoV). This pseudoknot was also shown to be essential for replication, and it
      has a conserved counterpart in every group 1 and group 2 coronavirus. In MHV and
      BCoV, the bulged stem-loop and pseudoknot are, in part, mutually exclusive,
      because of the overlap of the last segment of the stem-loop and stem 1 of the
      pseudoknot. This led us to hypothesize that they form a molecular switch,
      possibly regulating a transition occurring during viral RNA synthesis. We have
      now performed an extensive genetic analysis of the two components of this
      proposed switch. Our results define essential and nonessential components of
      these structures and establish the limits to which essential parts of each
      element can be destabilized prior to loss of function. Most notably, we have
      confirmed the interrelationship of the two putative switch elements.
      Additionally, we have identified a pseudoknot loop insertion mutation that
      appears to point to a genetic interaction between the pseudoknot and a distant
      region of the genome.

PMID- 14694099
TI  - The spacing between cysteines two and three of the LDL-A module of Tva is
      important for subgroup A avian sarcoma and leukosis virus entry.
AB  - Rong et al. have demonstrated previously that with a few substitutions, the
      fourth repeat of human low-density lipoprotein (hLDL-A4) receptor can
      functionally replace the LDL-A module of Tva, the cellular receptor for subgroup
      A avian sarcoma and leukosis virus (ASLV-A), in viral entry (L. Rong, K. Gendron,
      and P. Bates, Proc. Natl. Acad. Sci. USA 95:8467-8472, 1998). Here we have shown
      that swapping the amino terminus of hLDL repeat 5 (hLDL-A5) with that of Tva, in
      addition to the corresponding substitutions made in human LDL-A4, was required to
      convert hLDL-A5 into an efficient ASLV-A receptor. These results substantiated
      our previous findings regarding the role of the specific residues in the viral
      interaction domain of Tva and demonstrated the critical role of the amino
      terminus of the Tva LDL-A module in ASLV-A infection. Furthermore, we have shown
      that the residues between cysteines 2 and 3 of the Tva LDL-A module in a Tva/LDL
      A5 chimeric protein can be functionally replaced by the corresponding region of
      another LDL-A module, human LDL receptor-related protein repeat 22 (LDL-A22), to
      mediate efficient ASLV-A entry. Since the only conserved feature between the C2
      C3 region of LDL-A22 and the Tva LDL-A module is that both contain nine amino
      acids of which none are conserved, we conclude that the spacing between C2 and C3
      of the LDL-A module of Tva is an important determinant for ASLV-A entry. Thus,
      the present study provides strong evidence to support our hypothesis that one
      role of the N terminus of the LDL-A module of Tva is to allow proper folding and
      conformation of the protein for optimal interaction with the viral glycoprotein
      EnvA in ASLV-A entry.

PMID- 14694100
TI  - Effects of altering the transcription termination signals of respiratory
      syncytial virus on viral gene expression and growth in vitro and in vivo.
AB  - Nonsegmented negative-sense RNA viruses (mononegaviruses) control viral gene
      expression largely through a transcription gradient such that promoter-proximal
      genes are transcribed more abundantly than downstream genes. For some
      paramyxoviruses, naturally occurring differences in the levels of efficiency of
      transcription termination by various gene end (GE) signals provide an additional
      level of regulation of gene expression. The first two genes (NS1 and NS2) of
      respiratory syncytial virus (RSV) are particularly inefficient in termination. We
      investigated whether altering the termination efficiency (TE) of these two genes
      in infectious recombinant virus would affect transcription of promoter-proximal
      and promoter-distal genes, production of viral proteins, and viral replication in
      cell culture and in the respiratory tract of mice. Recombinant RSVs were
      constructed with mutations that increased or decreased the TE of the NS1 GE
      signal, increased that of the NS2 GE signal, or increased that of both signals.
      Increasing the TE of either or both GE signals resulted in decreased production
      of the related polycistronic readthrough mRNAs, which normally arise due to the
      failure of the viral polymerase to recognize the GE signal. This was accompanied
      by a small increase in the levels of monocistronic NS1 and NS2 mRNAs. Conversely,
      decreasing the TE of the NS1 GE increased the production of readthrough mRNAs
      concomitant with a decrease of monocistronic NS1 and NS2 mRNA levels. These
      changes were reflected in the levels of NS1 and NS2 protein. All of the mutant
      viruses displayed growth kinetics and virus yields similar to wild-type
      recombinant RSV (rA2) in both HEp-2 and Vero cells. In addition, all mutants grew
      similarly to rA2 in the upper- and lower-respiratory tract of BALB/c mice, though
      some of the mutants displayed slightly decreased replication. These data suggest
      that the natural inefficiencies of transcription termination by the NS1 and NS2
      GE signals do not play important roles in controlling the magnitude of RSV gene
      expression or the efficiency of virus replication. Furthermore, while changes in
      the TE of a GE signal clearly can affect the transcription of its gene as well as
      that of the one immediately downstream, these changes did not have a significant
      effect on the overall transcriptional gradient.

PMID- 14694101
TI  - Conserved C-terminal threonine of hepatitis C virus NS3 regulates autoproteolysis
      and prevents product inhibition.
AB  - Inspection of over 250 hepatitis C virus (HCV) genome sequences shows that a
      threonine is strictly conserved at the P1 position in the NS3-NS4A (NS3-4A)
      autoproteolysis junction, while a cysteine is maintained as the P1 residue in all
      of the putative trans cleavage sites (NS4A-4B, NS4B-5A, and NS5A-5B). To
      understand why T631 is conserved at the NS3-4A junction of HCV, a series of in
      vitro transcription-translation studies were carried out using wild-type and
      mutant (T631C) NS3-4A constructs bearing native, truncated, and mutant NS4A
      segments. The autocleavage of the wild-type junction was found to be dependent on
      the presence of the central cofactor domain of NS4A (residues 21 to 34). In
      contrast, all NS3-4A T631C mutant proteins underwent self-cleavage even in the
      absence of the cofactor. Subgenomic replicons derived from the Con1 strain of HCV
      and bearing the T631C mutation showed reduced levels of colony formation in
      transfection studies. Similarly, replicons derived from a second genotype 1b
      virus, HCV-N, demonstrated a comparable reduction in replication efficiency in
      transient-transfection assays. These data suggest that the threonine is conserved
      at position 631 because it serves two functions: (i) to slow processing at the
      NS3-4A cleavage site, ensuring proper intercalation of the NS4A cofactor with NS3
      prior to polyprotein scission, and (ii) to prevent subsequent product inhibition
      by the NS3 C terminus.

PMID- 14694102
TI  - Role of a mutation in human cytomegalovirus gene UL104 in resistance to
      benzimidazole ribonucleosides.
AB  - The benzimidazole D-ribonucleosides TCRB and BDCRB are potent and selective
      inhibitors of human cytomegalovirus (HCMV) replication. Two HCMV strains
      resistant to these compounds were selected and had resistance mutations in genes
      UL89 and UL56. Proteins encoded by these two genes are the two subunits of the
      HCMV "terminase" and are necessary for cleavage and packaging of viral genomic
      DNA, a process inhibited by TCRB and BDCRB. We now report that both strains also
      have a previously unidentified mutation in UL104, the HCMV portal protein. This
      mutation, which results in L21F substitution, was introduced into the genome of
      wild-type HCMV by utilizing a recently cloned genome of HCMV as a bacterial
      artificial chromosome. The virus with this mutation alone was not resistant to
      BDCRB, suggesting that this site is not involved in binding benzimidazole
      nucleosides. As in previous proposals for mutations in UL104 of murine
      cytomegalovirus and HCMV strains resistant to BAY 38-4766, we hypothesize that
      this mutation could compensate for conformational changes in mutant UL89 and UL56
      proteins, since the HCMV terminase is likely to interact with the portal protein
      during cleavage and packaging of genomic DNA.

PMID- 14694103
TI  - Nucleocapsid-RNA interactions are essential to structural stability but not to
      assembly of retroviruses.
AB  - The process of RNA incorporation into nascent virions is thought to be critical
      for efficient retroviral particle assembly and production. Here we show that
      human immunodeficiency virus type 1 mutant particles (which are highly unstable
      and break down soon after release from the cell) lacking nucleocapsid (NC) core
      protein-mediated RNA incorporation are produced efficiently and can be recovered
      at the normal density when viral protease function is abolished. These results
      demonstrate that RNA binding by Gag is not necessary for retroviral particle
      assembly. Rather, the RNA interaction with NC is critical for retroviral particle
      structural stability subsequent to release from the membrane and protease
      mediated Gag cleavage. Thus, the NC-RNA interaction, and not simply the presence
      of RNA, provides the virus with a structural function that is critical for stable
      retroviral particle architecture.

PMID- 14694104
TI  - Late domain-dependent inhibition of equine infectious anemia virus budding.
AB  - The Gag proteins of a number of different retroviruses contain late or L domains
      that promote the release of virions from the plasma membrane. Three types of L
      domains have been identified to date: Pro-Thr-Ala-Pro (PTAP), Pro-Pro-X-Tyr, and
      Tyr-Pro-Asp-Leu. It has previously been demonstrated that overexpression of the N
      terminal, E2-like domain of the endosomal sorting factor TSG101 (TSG-5') inhibits
      human immunodeficiency virus type 1 (HIV-1) release but does not affect the
      release of the PPPY-containing retrovirus murine leukemia virus (MLV), whereas
      overexpression of the C-terminal portion of TSG101 (TSG-3') potently disrupts
      both HIV-1 and MLV budding. In addition, it has been reported that, while the
      release of a number of retroviruses is disrupted by proteasome inhibitors, equine
      infectious anemia virus (EIAV) budding is not affected by these agents. In this
      study, we tested the ability of TSG-5', TSG-3', and full-length TSG101 (TSG-F)
      overexpression, a dominant negative form of the AAA ATPase Vps4, and proteasome
      inhibitors to disrupt the budding of EIAV particles bearing each of the three
      types of L domain. The results indicate that (i) inhibition by TSG-5' correlates
      with dependence on PTAP; (ii) the release of wild-type EIAV (EIAV/WT) is
      insensitive to TSG-3', whereas this C-terminal TSG101 fragment potently impairs
      the budding of EIAV when it is rendered PTAP or PPPY dependent; (iii) budding of
      all EIAV clones is blocked by dominant negative Vps4; and (iv) EIAV/WT release is
      not impaired by proteasome inhibitors, while EIAV/PTAP and EIAV/PPPY release is
      strongly disrupted by these compounds. These findings highlight intriguing
      similarities and differences in host factor utilization by retroviral L domains
      and suggest that the insensitivity of EIAV to proteasome inhibitors is conferred
      by the L domain itself and not by determinants in Gag outside the L domain.

PMID- 14694105
TI  - Expansion of a unique region in the Marek's disease virus genome occurs
      concomitantly with attenuation but is not sufficient to cause attenuation.
AB  - Pathogenic Marek's disease viruses (MDVs) have two head-to-tail copies of a 132
      bp repeat. As MDV is serially passaged in cell culture, the virus becomes
      attenuated and the number of copies of the 132-bp repeat increases from 2 to
      often more than 20 copies. To determine the role of the repeats in attenuation,
      we used five overlapping cosmid clones that spanned the MDV genome to
      reconstitute infectious virus (rMd5). By mutating the appropriate cosmids, we
      generated clones of infectious MDVs that contained zero copies of the 132-bp
      repeats, rMd5(Delta132); nine copies of the 132-bp repeats, rMd5(9-132); and nine
      copies of the 132-bp repeats inserted in the reverse orientation, rMd5(rev9-132).
      After two passages in cell culture, wild-type Md5, rMd5, and rMd5(Delta132) were
      stable. However, rMd5(9-132) and rMd5(rev9-132) contained a population of viruses
      that contained from 3 to over 20 copies of the repeats. A major 1.8-kb mRNA,
      containing two copies of the 132-bp repeat, was present in wild-type Md5 and rMd5
      but was not present in rMd5(Delta132), rMd5(9-132), rMd5(rev9-132), or an
      attenuated MDV. Instead, the RNAs transcribed from the 132-bp repeat region in
      rMd5(9-132) and rMd5(rev9-132) closely resembled the pattern of RNAs transcribed
      in attenuated MDVs. When inoculated into susceptible day-old chicks, all viruses
      produced various lesions. Thus, expansion of the number of copies of 132-bp
      repeats, which accompanies attenuation, is not sufficient in itself to attenuate
      pathogenic MDVs.

PMID- 14694106
TI  - Neutrality of the canonical NF-kappaB-dependent pathway for human and murine
      cytomegalovirus transcription and replication in vitro.
AB  - Cytomegalovirus (CMV) is known to rapidly induce activation of nuclear factor
      kappaB (NF-kappaB) after infection of fibroblast and macrophage cells. NF-kappaB
      response elements are present in the enhancer region of the CMV major immediate
      early promoter (MIEP), and activity of the MIEP is strongly upregulated by NF
      kappaB in transient-transfection assays. Here we investigate whether the NF
      kappaB-dependent pathway is required for initiating or potentiating human and
      murine CMV replication in vitro. We show that expression of a dominant negative
      mutant of the inhibitor of NF-kappaB-alpha (IkappaBalphaM) does not alter the
      replication kinetics of human or mouse CMV in cultured cells. In addition, mouse
      embryo fibroblasts genetically deficient for p65/RelA actually showed elevated
      levels of MCMV replication. Mutation of all NF-kappaB response elements within
      the enhancer of the MIEP in a recombinant mouse CMV containing the human MIEP
      (hMCMV-ES), which we have previously shown to replicate in murine fibroblasts
      with kinetics equivalent to that of wild-type mouse CMV, did not negatively
      affect replication in fibroblasts. Taken together, these data show that, for CMV
      replication in cultured fibroblasts activation of the canonical NF-kappaB pathway
      and binding of NF-kappaB to the MIEP are dispensable, and in the case of p65 may
      even interfere, thus uncovering a previously unrecognized level of complexity in
      the host regulatory network governing MIE gene expression in the context of a
      viral infection.

PMID- 14694107
TI  - Efficient intracellular assembly of papillomaviral vectors.
AB  - Although the papillomavirus structural proteins, L1 and L2, can spontaneously
      coassemble to form virus-like particles, currently available methods for
      production of L1/L2 particles capable of transducing reporter plasmids into
      mammalian cells are technically demanding and relatively low-yield. In this
      report, we describe a simple 293 cell transfection method for efficient
      intracellular production of papillomaviral-based gene transfer vectors carrying
      reporter plasmids. Using bovine papillomavirus type 1 (BPV1) and human
      papillomavirus type 16 as model papillomaviruses, we have developed a system for
      producing papillomaviral vector stocks with titers of several billion transducing
      units per milliliter. Production of these vectors requires both L1 and L2, and
      transduction can be prevented by papillomavirus-neutralizing antibodies. The
      stocks can be purified by an iodixanol (OptiPrep) gradient centrifugation
      procedure that is substantially more effective than standard cesium chloride
      gradient purification. Although earlier data had suggested a potential role for
      the viral early protein E2, we found that E2 protein expression did not enhance
      the intracellular production of BPV1 vectors. It was also possible to encapsidate
      reporter plasmids devoid of BPV1 DNA sequences. BPV1 vector production efficiency
      was significantly influenced by the size of the target plasmid being packaged.
      Use of 6-kb target plasmids resulted in BPV1 vector yields that were higher than
      those with target plasmids closer to the native 7.9-kb size of papillomavirus
      genomes. The results suggest that the intracellular assembly of papillomavirus
      structural proteins around heterologous reporter plasmids is surprisingly
      promiscuous and may be driven primarily by a size discrimination mechanism.

PMID- 14694108
TI  - The m4 gene of murine gammaherpesvirus modulates productive and latent infection
      in vivo.
AB  - Murine gammaherpesvirus 68 (MHV-68) infection of mice represents a viable small
      animal model for the study of gammaherpesvirus pathogenesis. MHV-76 is a deletion
      mutant of MHV-68, which lacks four MHV-68-specific genes (M1 to M4) and eight
      viral tRNA-like sequences at the 5' end of the genome. These genes are implicated
      in latency and/or immune evasion. Consequently, MHV-76 is attenuated in the acute
      phase of in vivo infection with respect to MHV-68. Little is known about the role
      of M4 in viral infection, except that it is expressed as an immediate-early/early
      transcript during lytic replication of MHV-68 in vitro. To elucidate the
      contribution M4 makes to in vivo pathogenesis, we created a novel MHV-76 mutant
      (MHV-76inM4), in which the region of MHV-68 coding for M4 and accompanying
      putative promoter elements were inserted into the 5' region of the MHV-76 genome.
      The growth of MHV-76inM4 in vitro was indistinguishable from that of MHV-76 and
      MHV-68. However, virus titers from MHV-76inM4-infected BALB/c mice were
      significantly increased with respect to MHV-76 at early times in the lung. In
      addition, at days 17 and 21 postinfection, there was a significant elevation in
      latent viral load in splenocytes of MHV-76inM4-infected mice compared to MHV-76.
      Like MHV-76-infected mice, MHV-76inM4-infected mice display no evidence of overt
      splenomegaly, a finding characteristic of MHV-68 infection. M4 expression in vivo
      was detectable during productive infection in the lung and during the
      establishment of latency in the spleen, but in general M4 was not detectable
      during long-term latency (day 100 postinfection).

PMID- 14694110
TI  - Human immunodeficiency virus type 1 Tat regulates endothelial cell actin
      cytoskeletal dynamics through PAK1 activation and oxidant production.
AB  - Human immunodeficiency virus type 1 Tat exerts prominent angiogenic effects which
      may lead to a variety of vasculopathic conditions in AIDS patients. Because
      endothelial cells undergo prominent cytoskeletal rearrangement during
      angiogenesis, we investigated the specific effects of Tat on the endothelial cell
      actin cytoskeleton. Glutathione S-transferase (GST)-Tat, at a level of 200 ng/ml
      (equivalent to 52 ng of Tat/ml), caused stress fiber disassembly, peripheral
      retraction, and ruffle formation in human umbilical vein endothelial cells
      (HUVEC) and human lung microvascular endothelial cells. At 600 ng of GST-Tat/ml
      (157 ng of Tat/ml), actin structures were lost, and severe cytoskeletal collapse
      occurred. In contrast, GST-Tat harboring mutations within either the cysteine
      rich or basic domains exerted minimal effects on the endothelial cytoskeleton.
      HUVEC expressing a DsRed-Tat fusion protein displayed similar actin
      rearrangements, followed by actin collapse, whereas neighboring nontransfected
      cells retained normal actin structures. Because active mutants of p21-activated
      kinase 1 (PAK1) induce identical changes in actin dynamics, we hypothesized that
      Tat exerts its cytoskeletal effects through PAK1. GST-Tat activated PAK1 within 5
      min, and adenovirus delivery of a kinase-dead PAK1 [PAK1(K298A)] completely
      prevented cytoskeletal collapse induced by GST-Tat or DsRed-Tat and also blocked
      downstream activation of c-Jun N-terminal kinase. Further, GST-Tat increased
      phosphorylation of the NADPH oxidase subunit p47(phox) and caused its rapid
      redistribution to membrane ruffles. PAK1(K298A) blocked p47(phox)
      phosphorylation, and interference with NADPH oxidase function through superoxide
      scavenging or through expression of a transdominant inhibitor, p67(V204A),
      prevented GST-Tat-induced alterations in the actin cytoskeleton. We conclude that
      Tat induces actin cytoskeletal rearrangements through PAK1 and downstream
      activation of the endothelial NADPH oxidase.

PMID- 14694109
TI  - Dual stimulation of Epstein-Barr Virus (EBV)-specific CD4+- and CD8+-T-cell
      responses by a chimeric antigen construct: potential therapeutic vaccine for EBV
      positive nasopharyngeal carcinoma.
AB  - Virus-associated malignancies are potential targets for immunotherapeutic
      vaccines aiming to stimulate T-cell responses against viral antigens expressed in
      tumor cells. Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma, a high
      incidence tumor in southern China, expresses a limited set of EBV proteins,
      including the nuclear antigen EBNA1, an abundant source of HLA class II
      restricted CD4(+) T-cell epitopes, and the latent membrane protein LMP2, a source
      of subdominant CD8(+) T-cell epitopes presented by HLA class I alleles common in
      the Chinese population. We used appropriately modified gene sequences from a
      Chinese EBV strain to generate a modified vaccinia virus Ankara recombinant, MVA
      EL, expressing the CD4 epitope-rich C-terminal domain of EBNA1 fused to full
      length LMP2. The endogenously expressed fusion protein EL is efficiently
      processed via the HLA class I pathway, and MVA-EL-infected dendritic cells
      selectively reactivate LMP2-specific CD8(+) memory T-cell responses from immune
      donors in vitro. Surprisingly, endogenously expressed EL also directly accesses
      the HLA class II presentation pathway and, unlike endogenously expressed EBNA1
      itself, efficiently reactivates CD4(+) memory T-cell responses in vitro. This
      unscheduled access to the HLA class II pathway is coincident with EL-mediated
      redirection of the EBNA1 domain from its native nuclear location to dense
      cytoplasmic patches. Given its immunogenicity to both CD4(+) and CD8(+) T cells,
      MVA-EL has potential as a therapeutic vaccine in the context of nasopharyngeal
      carcinoma.

PMID- 14694111
TI  - NS-3 protein of the Junonia coenia densovirus is essential for viral DNA
      replication in an Ld 652 cell line and Spodoptera littoralis larvae.
AB  - The genome of Junonia coenia densovirus (JcDNV) shares with members of the genus
      Densovirus the property of possessing structural (VP) and nonstructural (NS)
      genes in opposite orientations. The three NS genes located in the 5' half on one
      strand encode three NS proteins assumed to be involved in viral DNA replication:
      NS-1 and NS-2, which are common to all DNVs, and a 28-kDa polypeptide, NS-3, with
      a unique sequence. Whereas the essential role played by JcDNV NS-1 in viral DNA
      replication has been clearly established (C. Ding, M. Urabe, M. Bergoin, and R.
      M. Kotin, J. Virol. 76:338-345, 2002), nothing is known of the biological
      function(s) of NS-3. To investigate this function, we designed constructs derived
      from pBRJ, a plasmid encompassing an infectious sequence of JcDNV DNA (M.
      Jourdan, F. X. Jousset, M. Gervais, S. Skory, M. Bergoin, and B. Dumas, Virology
      179:403-409, 1990), with partial or complete deletion of NS-3 sequence or with
      the ATG initiation codon mutated by site-directed mutagenesis. Transfection of
      these constructs to sensitive Ld 652 cells or Spodoptera littoralis larvae
      prevented the accomplishment of a productive cycle. We clearly established that
      the blocking of the replicative cycle in the absence of NS-3 expression occurred
      at the level of viral DNA replication. Replication of viral DNA could be restored
      by cotransfecting Ld 652 cells with a plasmid expressing JcDNV-NS-3 protein in
      trans. Time course analysis showed that NS-3 is produced early (6 h
      posttransfection) in the replicative cycle, and its production parallels that of
      replicative-form viral DNA. Finally, we present evidence that NS-1 and NS-2
      proteins are synthesized at apparently the same levels whether or not NS-3 is
      expressed.

PMID- 14694112
TI  - DC-SIGN from African green monkeys is expressed in lymph nodes and mediates
      infection in trans of simian immunodeficiency virus SIVagm.
AB  - African green monkeys (AGMs) infected by simian immunodeficiency virus (SIV)
      SIVagm are resistant to AIDS. SIVagm-infected AGMs exhibit levels of viremia
      similar to those described during pathogenic human immunodeficiency virus type 1
      (HIV-1) and SIVmac infections in humans and macaques, respectively, but contain
      lower viral loads in their lymph nodes. We addressed the potential role of
      dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin
      (DC-SIGN; CD209) in viral dissemination. In previous studies, it has been shown
      that human DC-SIGN and macaque DC-SIGN allow transmission of HIV and SIVmac to T
      cells. Here, we looked at the ability of DC-SIGN derived from AGM lymph nodes to
      interact with SIVagm. We show that DC-SIGN-expressing cells are present mainly in
      the medulla and often within the cortex and/or paracortex of AGM lymph nodes. We
      describe the isolation and characterization of at least three isoforms of dc-sign
      mRNA in lymph nodes of AGMs. The predicted amino acid sequence from the
      predominant mRNA isoform, DC-SIGNagm1, is 92 and 99% identical to the
      corresponding human and rhesus macaque DC-SIGN amino acid sequences,
      respectively. DC-SIGNagm1 is characterized by the lack of the fourth motif in the
      repeat domain. This deletion was also detected in the dc-sign gene derived from
      thirteen animals belonging to five other African monkey species and from four
      macaques (Macaca fascicularis and M. mulatta). Despite three- to seven-amino-acid
      modifications compared to DC-SIGNmac, DC-SIGNagm1 allows transmission of SIVagm
      to T cells. Furthermore, AGM monocyte-derived dendritic cells (MDDC) expressed at
      least 100,000 DC-SIGN molecules and were able to transmit SIVagm to T cells. At a
      low multiplicity of infection (10(-5) 50% tissue culture infective doses/cell),
      viral transmission by AGM MDDC was mainly DC-SIGN dependent. The present study
      reveals that DC-SIGN from a natural host species of SIV has the ability to act as
      an efficient attachment and transmission factor for SIVagm and suggests the
      absence of a direct link between this ability and viral load levels in lymph
      nodes.

PMID- 14694113
TI  - Role of the ectodomain of the gp41 transmembrane envelope protein of human
      immunodeficiency virus type 1 in late steps of the membrane fusion process.
AB  - The membrane fusion process mediated by the gp41 transmembrane envelope
      glycoprotein of the human immunodeficiency virus type 1 (HIV-1) was addressed by
      a flow cytometry assay detecting exchanges of fluorescent membrane probes (DiI
      and DiO) between cells expressing the HIV-1 envelope proteins (Env) and target
      cells. Double-fluorescent cells were detected when target cells expressed the
      type of chemokine receptor, CXCR4 or CCR5, matching the type of gp120 surface
      envelope protein, X4 or R5, respectively. Background levels of double-fluorescent
      cells were observed when the gp120-receptor interaction was blocked by AMD3100, a
      CXCR4 antagonist. The L568A mutation in the N-terminal heptad repeat (HR1) of
      gp41 resulted in parallel inhibition of the formation of syncytia and double
      fluorescent cells, indicating that gp41 had a direct role in the exchange of
      fluorescent probes. In contrast, three mutations in the loop region of the gp41
      ectodomain, located on either side of the Cys-(X)(5)-Cys motif (W596 M and W610A)
      or at the distal end of HR1 (D589L), had limited or no apparent effect on
      membrane lipid mixing between Env(+) and target cells, while they blocked
      formation of syncytia and markedly reduced the exchanges of cytoplasmic
      fluorescent probes. The loop region could therefore have a direct or indirect
      role in events occurring after the merging of membranes, such as the formation or
      dilation of fusion pores. Two types of inhibitors of HIV-1 entry, the gp41
      derived peptide T20 and the betulinic acid derivative RPR103611, had limited
      effects on membrane exchanges at concentrations blocking or markedly reducing
      syncytium formation. This finding confirmed that T20 can inhibit the late steps
      of membrane fusion (post-lipid mixing) and brought forth an indirect argument for
      the role of the gp41 loop region in these steps, as mutations conferring
      resistance to RPR103611V were mapped in this region (I595S or L602H).

PMID- 14694114
TI  - Functional analysis of the human papillomavirus type 16 E1=E4 protein provides a
      mechanism for in vivo and in vitro keratin filament reorganization.
AB  - High-risk human papillomaviruses, such as human papillomavirus type 16 (HPV16),
      are the primary cause of cervical cancer. The HPV16 E1=E4 protein associates with
      keratin intermediate filaments and causes network collapse when expressed in
      epithelial cells in vitro. Here, we show that keratin association and network
      reorganization also occur in vivo in low-grade cervical neoplasia caused by
      HPV16. The 16E1=E4 protein binds to keratins directly and interacts strongly with
      keratin 18, a member of the type I intermediate-filament family. By contrast,
      16E1=E4 bound only weakly to keratin 8, a type II intermediate-filament protein,
      and showed no detectable affinity for the type III protein, vimentin. The N
      terminal 16 amino acids of the 16E1=E4 protein, which contains the YPLLXLL motif
      that is conserved among supergroup A viruses, were sufficient to target green
      fluorescent protein to the keratin network. When expressed in the SiHa cervical
      epithelial cell line, the full-length 16E1=E4 protein caused an almost total
      inhibition of keratin dynamics, despite the phosphorylation of keratin 18 at
      serine 33, which normally leads to 14-3-3-mediated keratin solubilization. Mutant
      16E1=E4 proteins which lack the LLKLL motif, or which have lost amino acids from
      their C termini, and which were compromised in the ability to associate with
      keratins did not disturb normal keratin dynamics. 16E1=E4 was found to exist as
      dimers and hexamers, whereas a C-terminal deletion mutant (16E1=E4Delta87-92)
      existed as monomers and formed multimeric structures only poorly. Considered
      together, our results suggest that by associating with keratins through its N
      terminus, and by associating with itself through its C terminus, 16E1=E4 may act
      as a keratin cross-linker and prevent the movement of keratins between the
      soluble and insoluble compartments. The increase in avidity associated with
      multimeric binding may contribute to the ability of 16E1=E4 to sequester its
      cellular targets in the cytoplasm.

PMID- 14694115
TI  - Nipah virus: vaccination and passive protection studies in a hamster model.
AB  - Nipah virus, a member of the paramyxovirus family, was first isolated and
      identified in 1999 when the virus crossed the species barrier from fruit bats to
      pigs and then infected humans, inducing an encephalitis with up to 40% mortality.
      At present there is no prophylaxis for Nipah virus. We investigated the
      possibility of vaccination and passive transfer of antibodies as interventions
      against this disease. We show that both of the Nipah virus glycoproteins (G and
      F) when expressed as vaccinia virus recombinants induced an immune response in
      hamsters which protected against a lethal challenge by Nipah virus. Similarly,
      passive transfer of antibody induced by either of the glycoproteins protected the
      animals. In both the active and passive immunization studies, however, the
      challenge virus was capable of hyperimmunizing the vaccinated animals, suggesting
      that although the virus replicates under these conditions, the immune system can
      eventually control the infection.

PMID- 14694116
TI  - Gamma interferon-mediated inflammation is associated with lack of protection from
      intravaginal simian immunodeficiency virus SIVmac239 challenge in simian-human
      immunodeficiency virus 89.6-immunized rhesus macaques.
AB  - Although gamma interferon (IFN-gamma) is a key mediator of antiviral defenses, it
      is also a mediator of inflammation. As inflammation can drive lentiviral
      replication, we sought to determine the relationship between IFN-gamma-related
      host immune responses and challenge virus replication in lymphoid tissues of
      simian-human immunodeficiency virus 89.6 (SHIV89.6)-vaccinated and unvaccinated
      rhesus macaques 6 months after challenge with simian immunodeficiency virus
      SIVmac239. Vaccinated-protected monkeys had low tissue viral RNA (vRNA) levels,
      vaccinated-unprotected animals had moderate tissue vRNA levels, and unvaccinated
      animals had high tissue vRNA levels. The long-term challenge outcome in
      vaccinated monkeys was correlated with the relative balance between SIV-specific
      IFN-gamma T-cell responses and nonspecific IFN-gamma-driven inflammation.
      Vaccinated-protected monkeys had slightly increased tissue IFN-gamma mRNA levels
      and a high frequency of IFN-gamma-secreting T cells responding to in vitro SIVgag
      peptide stimulation; thus, it is likely that they could develop effective anti
      SIV cytotoxic T lymphocytes in vivo. In contrast, both high tissue IFN-gamma mRNA
      levels and strong in vitro SIV-specific IFN-gamma T-cell responses were detected
      in lymphoid tissues of vaccinated-unprotected monkeys. Unvaccinated monkeys had
      increased tissue IFN-gamma mRNA levels but weak in vitro anti-SIV IFN-gamma T
      cell responses. In addition, in lymphoid tissues of vaccinated-unprotected and
      unvaccinated monkeys, the increased IFN-gamma mRNA levels were associated with
      increased Mig/CXCL9, IP-10/CXCL10, and CXCR3 mRNA levels, suggesting that
      increased Mig/CXCL9 and IP-10/CXCL10 expression resulted in recruitment of
      CXCR3(+) activated T cells. Thus, IFN-gamma-driven inflammation promotes SIV
      replication in vaccinated-unprotected and unvaccinated monkeys. Unlike all
      unvaccinated monkeys, most monkeys vaccinated with SHIV89.6 did not develop IFN
      gamma-driven inflammation, but they did develop effective antiviral CD8(+)-T-cell
      responses.

PMID- 14694117
TI  - Evidence for frequent recombination within species human enterovirus B based on
      complete genomic sequences of all thirty-seven serotypes.
AB  - The species Human enterovirus B (HEV-B) in the family Picornaviridae consists of
      coxsackievirus A9; coxsackieviruses B1 to B6; echoviruses 1 to 7, 9, 11 to 21, 24
      to 27, and 29 to 33; and enteroviruses 69 and 73. We have determined complete
      genome sequences for the remaining 22 HEV-B serotypes whose sequences were not
      represented in public databases and analyzed these in conjunction with previously
      available complete sequences in GenBank. Members of HEV-B were monophyletic
      relative to all other human enterovirus species in all regions of the genome
      except in the 5'-nontranslated region (NTR), where they are known to cluster with
      members of HEV-A. Within HEV-B, phylogenies constructed from the structural (P1)
      and nonstructural regions of the genome (P2 and P3) are incongruent, suggesting
      that recombination had occurred. Similarity plots and bootscanning analysis
      across the complete genome identified multiple sites at which the phylogeny of a
      given strain's sequence shifted, indicating potential recombination points. These
      points are distributed in the 5'-NTR and throughout P2 and P3, but no sites with
      >80% bootstrap support were identified within the capsid. Individual sequence
      comparisons and phylogenetic analyses suggest that members of HEV-B have
      recombined with one another on multiple occasions, resulting in a complex mosaic
      of sequences derived from multiple parental viruses in the nonstructural regions
      of the genome. We conclude that RNA recombination is a common mechanism for
      enterovirus evolution and that recombination within the nonstructural regions of
      the genome (P2 and P3) has been observed only among members of the same species.

PMID- 14694118
TI  - Potential selection of LMP1 variants in nasopharyngeal carcinoma.
AB  - Seven distinct sequence variants of the Epstein-Barr virus latent membrane
      protein 1 (LMP1) have been identified by distinguishing amino acid changes in the
      carboxy-terminal domain. In this study the transmembrane domains are shown to
      segregate identically with the distinct carboxy-terminal amino acid sequences.
      Since strains of LMP1 have been shown to differ in abundance between blood and
      throat washes, nasopharyngeal carcinomas (NPCs) from areas of endemicity and
      nonendemicity with matching blood were analyzed by using a heteroduplex tracking
      assay to distinguish LMP1 variants. Striking differences were found between the
      compartments with the Ch1 strain prevalent in the NPCs from areas of endemicity
      and nonendemicity and the B958 strain prevalent in the blood of the endemic
      samples, whereas multiple strains of LMP1 were prevalent in the blood of the
      nonendemic samples. The possible selection against the B958 strain appearing in
      the tumor was highly significant (P < 0.0001). Sequence analysis of the full
      length LMP1 variants revealed changes in many of the known and computer-predicted
      HLA-restricted epitopes with changes in key positions in multiple, potential
      epitopes for the specific HLA of the patients. These amino acid substitutions at
      key positions in the LMP1 epitopes may result in a reduced cytotoxic-T-lymphocyte
      response. These data indicate that strains with specific variants of LMP1 are
      more likely to be found in NPC. The predominance of specific LMP1 variants in NPC
      could reflect differences in the biologic or molecular properties of the distinct
      forms of LMP1 or possible immune selection.

PMID- 14694119
TI  - Differential effects of actin cytoskeleton dynamics on equine infectious anemia
      virus particle production.
AB  - Retrovirus assembly and budding involve a highly dynamic and concerted
      interaction of viral and cellular proteins. Previous studies have shown that
      retroviral Gag proteins interact with actin filaments, but the significance of
      these interactions remains to be defined. Using equine infectious anemia virus
      (EIAV), we now demonstrate differential effects of cellular actin dynamics at
      distinct stages of retrovirus assembly and budding. First, virion production was
      reduced when EIAV-infected cells were treated with phallacidin, a cell-permeable
      reagent that stabilizes actin filaments by slowing down their depolymerization.
      Confocal microscopy confirmed that the inhibition of EIAV production correlated
      temporally over several days with the incorporation dynamics of phallacidin into
      the actin cytoskeleton. Although the overall structure of the actin cytoskeleton
      and expression of viral protein appeared to be unaffected, phallacidin treatment
      dramatically reduced the amount of full-length Gag protein associated with the
      actin cytoskeleton. These data suggest that an association of full-length Gag
      proteins with de novo actin filaments might contribute to Gag assembly and
      budding. On the other hand, virion production was enhanced when EIAV-infected
      cells were incubated briefly (2 h) with the actin-depolymerizing drugs
      cytochalasin D and latrunculin B. Interestingly, the enhanced virion production
      induced by cytochalasin D required a functional late (L) domain, either the EIAV
      YPDL L-domain or the proline-rich L domains derived from human immunodeficiency
      virus type 1 or Rous sarcoma virus, respectively. Thus, depolymerization of actin
      filaments may be a common function mediated by retrovirus L domains during late
      stages of viral budding. Taken together, these observations indicate that dynamic
      actin polymerization and depolymerization may be associated with different stages
      of viral production.

PMID- 14694120
TI  - A reovirus of the fungus Cryphonectria parasitica that is infectious as particles
      and related to the coltivirus genus of animal pathogens.
AB  - RNA viruses of filamentous fungi fall into two broad categories, those that
      contain double-stranded RNA (dsRNA) genomes in rigid particles and those that are
      more closely related to positive-sense, single-stranded RNA viruses with dsRNA
      replicative intermediates found within lipid vesicles. Effective infectivity
      systems have been described for the latter, using RNA transcripts, but not for
      the former. We report the characterization of a reovirus from Cryphonectria
      parasitica, the filamentous fungus that causes chestnut blight disease. The virus
      substantially reduces the virulence of the fungus and results in dramatically
      altered colony morphology, as well as changes in other associated fungal traits,
      relative to the virus-free isogenic strain. Virus particles from infected
      mycelium contained 11 segments of dsRNA and showed characteristics typical of the
      family Reoviridae. Sequences of the largest three segments revealed that the
      virus is closely related to the Coltivirus genus of animal pathogens, which
      includes the human pathogen Colorado tick fever virus. The introduction of
      purified virus particles into protoplasts from virus-free isolates of the fungus
      resulted in a newly infected mycelium with the same morphology and virus
      composition as the original virus-infected isolate. This represents the
      completion of Koch's postulates for a true dsRNA virus from a filamentous fungus
      and the description of a definitive fungal member of the family Reoviridae.

PMID- 14694121
TI  - Genome structure and thymic expression of an endogenous retrovirus in zebrafish.
AB  - In a search for previously unknown genes that are required for lymphocyte
      development in zebrafish, a retroviral sequence was identified in a subtracted
      thymus cDNA library and in genomic DNA libraries. The provirus is 11.2 kb and
      contains intact open reading frames for the gag, pol, and env genes, as well as
      nearly identical flanking long terminal repeat sequences. As determined by in
      situ hybridization, the thymus appears to be a major tissue for retroviral
      expression in both larval and adult fish. Several viral transcripts were found by
      Northern blotting in the adult thymus. The provirus was found at the same genomic
      locus in sperm from four fish, suggesting that it is an endogenous retrovirus.
      Phylogenetic analysis indicates that it is closest to, yet distinct from, the
      cluster of murine leukemia virus-related retroviruses, suggesting that this virus
      represents a new group of retroviruses.

PMID- 14694123
TI  - Small-molecule inhibition of human immunodeficiency virus type 1 replication by
      specific targeting of the final step of virion maturation.
AB  - Despite the effectiveness of currently available human immunodeficiency virus
      type 1 (HIV-1) therapies, a continuing need exists for new drugs to treat HIV-1
      infection. We investigated the mechanism by which 3-O-[3',3'-dimethylsuccinyl]
      betulinic acid (DSB) inhibits HIV-1 replication. DSB functions at a late stage of
      the virus life cycle but does not inhibit the HIV-1 protease in vitro or
      interfere with virus assembly or release. DSB specifically delays the cleavage of
      Gag between the capsid (CA) and p2, resulting in delayed formation of the mature
      viral core and reduced HIV-1 infectivity. Replication of simian immunodeficiency
      virus (SIV) was resistant to DSB; however, a chimeric SIV carrying CA-p2
      sequences from HIV-1 was inhibited by the drug, indicating that susceptibility to
      DSB maps to the CA-p2 region of the HIV-1 Gag protein. A single point mutation at
      the CA-p2 cleavage site of HIV-1 conferred strong resistance to DSB, confirming
      the target of the drug. HIV-1 strains that are resistant to a variety of protease
      inhibitors were sensitive to DSB. These findings indicate that DSB specifically
      protects the CA-p2 cleavage site from processing by the viral protease during
      virion maturation, thereby revealing a novel mechanism for pharmacologic
      inhibition of HIV-1 replication.

PMID- 14694122
TI  - PEGylation of a vesicular stomatitis virus G pseudotyped lentivirus vector
      prevents inactivation in serum.
AB  - One disadvantage of vesicular stomatitis virus G (VSV-G) pseudotyped lentivirus
      vectors for clinical application is inactivation of the vector by human serum
      complement. To prevent this, monomethoxypoly(ethylene) glycol was conjugated to a
      VSV-G-human immunodeficiency virus vector expressing Escherichia coli beta
      galactosidase. The modification did not affect transduction efficiency in vitro
      and protected the vector from inactivation in complement-active human and mouse
      sera. Blood from mice dosed intravenously with either the unmodified or the
      PEGylated virus particles was assayed for active vector by a limiting-dilution
      assay to evaluate transduction efficiency and for p24, an indicator of the total
      number of virus particles present. PEGylation extended the circulation half-life
      of active vector by a factor of 5 and reduced the rate of vector inactivation in
      the serum by a factor of 1,000. Pharmacokinetic profiles for the total number of
      virus particles present in the circulation were unaffected by PEGylation.
      Modification of the vector with poly(ethylene) glycol significantly enhanced
      transduction efficiency in the bone marrow and in the spleen 14 days after
      systemic administration of the virus. These results, in concert with the
      pharmacokinetic profiles, indicate that PEGylation does protect the virus from
      inactivation in the serum and, as a result, improves the transduction efficiency
      of VSV-G pseudotyped lentivirus vectors in susceptible organs in vivo.

PMID- 14694124
TI  - Nuclear localization of avian polyomavirus structural protein VP1 is a
      prerequisite for the formation of virus-like particles.
AB  - Virions of polyomaviruses consist of the major structural protein VP1, the minor
      structural proteins VP2 and VP3, and the viral genome associated with histones.
      An additional structural protein, VP4, is present in avian polyomavirus (APV)
      particles. As it had been reported that expression of APV VP1 in insect cells did
      not result in the formation of virus-like particles (VLP), the prerequisites for
      particle formation were analyzed. To this end, recombinant influenza viruses were
      created to (co)express the structural proteins of APV in chicken embryo cells,
      permissive for APV replication. VP1 expressed individually or coexpressed with
      VP4 did not result in VLP formation; both proteins (co)localized in the
      cytoplasm. Transport of VP1, or the VP1-VP4 complex, into the nucleus was
      facilitated by the coexpression of VP3 and resulted in the formation of VLP.
      Accordingly, a mutant APV VP1 carrying the N-terminal nuclear localization signal
      of simian virus 40 VP1 was transported to the nucleus and assembled into VLP.
      These results support a model of APV capsid assembly in which complexes of the
      structural proteins VP1, VP3 (or VP2), and VP4, formed within the cytoplasm, are
      transported to the nucleus using the nuclear localization signal of VP3 (or VP2);
      there, capsid formation is induced by the nuclear environment.

PMID- 14694125
TI  - Characterization of the inhibition of hepatitis C virus RNA replication by
      nonnucleosides.
AB  - The RNA-dependent RNA polymerase of hepatitis C virus (HCV) is necessary for the
      replication of viral RNA and thus represents an attractive target for drug
      development. Several structural classes of nonnucleoside inhibitors (NNIs) of HCV
      RNA polymerase have been described, including a promising series of
      benzothiadiazine compounds that efficiently block replication of HCV subgenomic
      replicons in tissue culture. In this work we report the selection of replicons
      resistant to inhibition by the benzothiadiazine class of NNIs. Four different
      single mutations were identified in separate clones, and all four map to the RNA
      polymerase gene, validating the polymerase as the antiviral target of inhibition.
      The mutations (M414T, C451R, G558R, and H95R) render the HCV replicons resistant
      to inhibition by benzothiadiazines, though the mutant replicons remain sensitive
      to inhibition by other nucleoside and NNIs of the HCV RNA polymerase.
      Additionally, cross-resistance studies and synergistic inhibition of the enzyme
      by combinations of a benzimidazole and a benzothiadiazine indicate the existence
      of nonoverlapping binding sites for these two structural classes of inhibitors.

PMID- 14694127
TI  - Persistent infection with ebola virus under conditions of partial immunity.
AB  - Ebola hemorrhagic fever in humans is associated with high mortality; however,
      some infected hosts clear the virus and recover. The mechanisms by which this
      occurs and the correlates of protective immunity are not well defined. Using a
      mouse model, we determined the role of the immune system in clearance of and
      protection against Ebola virus. All CD8 T-cell-deficient mice succumbed to
      subcutaneous infection and had high viral antigen titers in tissues, whereas mice
      deficient in B cells or CD4 T cells cleared infection and survived, suggesting
      that CD8 T cells, independent of CD4 T cells and antibodies, are critical to
      protection against subcutaneous Ebola virus infection. B-cell-deficient mice that
      survived the primary subcutaneous infection (vaccinated mice) transiently
      depleted or not depleted of CD4 T cells also survived lethal intraperitoneal
      rechallenge for >/==" BORDER="0">25 days. However, all vaccinated B-cell
      deficient mice depleted of CD8 T cells had high viral antigen titers in tissues
      following intraperitoneal rechallenge and died within 6 days, suggesting that
      memory CD8 T cells by themselves can protect mice from early death. Surprisingly,
      vaccinated B-cell-deficient mice, after initially clearing the infection, were
      found to have viral antigens in tissues later (day 120 to 150 post
      intraperitoneal infection). Furthermore, following intraperitoneal rechallenge,
      vaccinated B-cell-deficient mice that were transiently depleted of CD4 T cells
      had high levels of viral antigen in tissues earlier (days 50 to 70) than
      vaccinated undepleted mice. This demonstrates that under certain immunodeficiency
      conditions, Ebola virus can persist and that loss of primed CD4 T cells
      accelerates the course of persistent infections. These data show that CD8 T cells
      play an important role in protection against acute disease, while both CD4 T
      cells and antibodies are required for long-term protection, and they provide
      evidence of persistent infection by Ebola virus suggesting that under certain
      conditions of immunodeficiency a host can harbor virus for prolonged periods,
      potentially acting as a reservoir.

PMID- 14694126
TI  - Secretory immunoglobulin A antibodies against the sigma1 outer capsid protein of
      reovirus type 1 Lang prevent infection of mouse Peyer's patches.
AB  - Reovirus type 1 Lang (T1L) adheres to M cells in the follicle-associated
      epithelium of mouse intestine and exploits the transport activity of M cells to
      enter and infect the Peyer's patch mucosa. Adult mice that have previously
      cleared a reovirus T1L infection have virus-specific immunoglobulin G (IgG) in
      serum and IgA in secretions and are protected against reinfection. Our aim in
      this study was to determine whether secretory IgA is sufficient for protection of
      Peyer's patches against oral reovirus challenge and, if so, against which
      reovirus antigen(s) the IgA may be directed. Monoclonal antibodies (MAbs) of the
      IgA isotype, directed against the sigma1 protein of reovirus T1L, the viral
      adhesin, were produced and tested along with other, existing IgA and IgG MAbs
      against reovirus T1L outer capsid proteins. Anti-sigma1 IgA and IgG MAbs
      neutralized reovirus T1L in L cell plaque reduction assays and inhibited T1L
      adherence to L cells and Caco-2(BBe) intestinal epithelial cells in vitro, but
      MAbs against other proteins did not. Passive oral administration of anti-sigma1
      IgA and IgG MAbs prevented Peyer's patch infection in adult mice, but other MAbs
      did not. When anti-sigma1 IgA and IgG MAbs were produced in mice from hybridoma
      backpack tumors, however, the IgA prevented Peyer's patch infection, but the IgG
      did not. The results provide evidence that neutralizing IgA antibodies specific
      for the sigma1 protein are protective in vitro and in vivo and that the presence
      of these antibodies in intestinal secretions is sufficient for protection against
      entry of reovirus T1L into Peyer's patches.

PMID- 14694128
TI  - Continued production of drug-sensitive human immunodeficiency virus type 1 in
      children on combination antiretroviral therapy who have undetectable viral loads.
AB  - Highly active antiretroviral therapy (HAART) can suppress plasma human
      immunodeficiency virus type 1 (HIV-1) levels to below the detection limit of
      ultrasensitive clinical assays. However, HIV-1 persists in cellular reservoirs,
      and in adults, persistent low-level viremia is detected with more sensitive
      assays. The nature of this viremia is poorly understood, and it is unclear
      whether viremia persists in children on HAART, particularly those who start
      therapy shortly after birth. We therefore developed a reverse transcriptase PCR
      (RT-PCR) assay that allows genotyping of HIV-1 protease even when viremia is
      present at levels as low as 5 copies of HIV-1 RNA/ml. We demonstrated that
      viremia persists in children with plasma virus levels below the limit of
      detection of clinical assays. Viremia was detected even in children who began
      HAART in early infancy and maintained such strong suppression of viremia that HIV
      1-specific antibody responses were absent or minimal. The low-level plasma virus
      lacked protease inhibitor resistance mutations despite the frequent use of
      nelfinavir, which has a low mutational barrier to resistance. Protease sequences
      resembled those of viruses in the latent reservoir in resting CD4(+) T cells.
      Thus, in most children on HAART with clinically undetectable viremia, there is
      continued virus production without evolution of resistance in the protease gene.

PMID- 14694129
TI  - Sequence motifs involved in the regulation of discontinuous coronavirus
      subgenomic RNA synthesis.
AB  - Coronavirus transcription leads to the synthesis of a nested set of mRNAs with a
      leader sequence derived from the 5' end of the genome. The mRNAs are produced by
      a discontinuous transcription in which the leader is linked to the mRNA coding
      sequences. This process is regulated by transcription-regulating sequences (TRSs)
      preceding each mRNA, including a highly conserved core sequence (CS) with high
      identity to sequences present in the virus genome and at the 3' end of the leader
      (TRS-L). The role of TRSs was analyzed by reverse genetics using a full-length
      infectious coronavirus cDNA and site-directed mutagenesis of the CS. The
      canonical CS-B was nonessential for the generation of subgenomic mRNAs (sgmRNAs),
      but its presence led to transcription levels at least 10(3)-fold higher than
      those in its absence. The data obtained are compatible with a transcription
      mechanism including three steps: (i) formation of 5'-3' complexes in the genomic
      RNA, (ii) base-pairing scanning of the nascent negative RNA strand by the TRS-L,
      and (iii) template switching during synthesis of the negative strand to complete
      the negative sgRNA. This template switch takes place after copying the CS
      sequence and was predicted in silico based on high base-pairing score between the
      nascent negative RNA strand and the TRS-L and minimum DeltaG.

PMID- 14694130
TI  - Imparting temperature sensitivity and attenuation in ferrets to A/Puerto
      Rico/8/34 influenza virus by transferring the genetic signature for temperature
      sensitivity from cold-adapted A/Ann Arbor/6/60.
AB  - The four temperature-sensitive (ts) loci identified in the PB1 and PB2 gene
      segments of cold-adapted A/Ann Arbor/6/60 influenza virus, the master donor virus
      for influenza A virus (MDV-A) FluMist vaccines, were introduced into a divergent
      A/Puerto Rico/8/34 influenza virus strain. Recombinant A/Puerto Rico/8/34 virus
      with these four introduced ts loci exhibited both ts and att phenotypes similar
      to those of MDV-A, which could be used as a donor virus for manufacturing large
      quantities of inactivated influenza virus vaccine against potential pandemic
      strains.

PMID- 14694131
TI  - Production of novel ebola virus-like particles from cDNAs: an alternative to
      ebola virus generation by reverse genetics.
AB  - We established a plasmid-based system for generating infectious Ebola virus-like
      particles (VLPs), which contain an Ebola virus-like minigenome consisting of a
      negative-sense copy of the green fluorescent protein gene. This system produced
      nearly 10(3) infectious particles per ml of supernatant, equivalent to the titer
      of Ebola virus generated by a reverse genetics system. Interestingly, infectious
      Ebola VLPs were generated, even without expression of VP24. Transmission and
      scanning electron microscopic analyses showed that the morphology of the Ebola
      VLPs was indistinguishable from that of authentic Ebola virus. Thus, this system
      allows us to study Ebola virus entry, replication, and assembly without biosafety
      level 4 containment. Furthermore, it may be useful in vaccine production against
      this highly pathogenic agent.

PMID- 14694132
TI  - Capsid-dependent and -independent postentry restriction of primate lentivirus
      tropism in rodent cells.
AB  - Retrovirus tropism can be restricted by cellular factors such as Fv1, Ref1, and
      Lv1 that inhibit infection by targeting the incoming viral capsid. Here, we show
      that rodent cells exhibit differential sensitivity to infection by vesicular
      stomatitis virus G-pseudotyped lentiviruses and that differences between human
      immunodeficiency virus type 1 and simian immunodeficiency virus (SIVmac)
      infectivity are sometimes, but not always, governed by determinants in capsid-p2.
      In at least one case, resistance to SIVmac infection could be eliminated by
      saturation of target cells with noninfectious SIVmac particles. However, cross
      saturation experiments and analysis of Fv1-null cells engineered to express
      natural or artificial Fv1 proteins revealed that lentivirus restriction in mouse
      cells is independent of Fv1. Overall, these findings indicate that novel
      restriction factors in rodents can modulate sensitivity to specific primate
      lentiviruses.

PMID- 14694133
TI  - Increased G-->A transition frequencies displayed by primer grip mutants of human
      immunodeficiency virus type 1 reverse transcriptase.
AB  - A genetic screen based on the blue-white beta-galactosidase complementation assay
      designed to detect G-->A mutations arising during RNA-dependent DNA synthesis was
      used to compare the fidelity of mutant human immunodeficiency virus type 1
      reverse transcriptases (RTs) with the mutations M230L and M230I with the wild
      type enzyme, in the presence of biased deoxynucleoside triphosphate (dNTP) pools.
      The mutant RTs with the M230L and M230I changes were found to be 20 to 70 times
      less faithful than the wild-type RT in the presence of low [dCTP]/[dTTP] ratios
      but showed similar fidelity in assays carried out with equimolar concentrations
      of each nucleotide. Biased dNTP pools led to short tandem repeat deletions in the
      target sequence, which were also detectable with the assay. However, deletion
      frequencies were similar for all of the RTs tested. The reported data suggest
      that RT pausing due to the low dNTP levels available in the RT reaction mixture
      facilitates strand transfer, in a process that is not necessarily mediated by
      nucleotide misinsertion.

PMID- 14694134
TI  - Mucosal and systemic immune responses to a human immunodeficiency virus type 1
      epitope induced upon vaginal infection with a recombinant influenza A virus.
AB  - The humoral and cellular immune responses in the genital mucosa likely play an
      important role in the prevention of sexually transmitted infections, including
      infection with human immunodeficiency virus type 1 (HIV-1). Here we show that
      vaginal infection of progesterone-treated BALB/c mice with a recombinant
      influenza virus bearing the immunodominant P18IIIB cytotoxic T-lymphocyte (CTL)
      epitope of the gp160 envelope protein from an HIV-1 IIIB isolate (P18IIIB;
      RIQRGPGRAFVTIGK) can induce a specific immune response in regional mucosal lymph
      nodes, as well as in a systemic site (the spleen). A single inoculation of mice
      with the recombinant influenza virus induced long-lasting (at least 5 months)
      antigen-specific CTL memory detectable as a rapid recall of effector CTLs upon
      vaginal infection with recombinant vaccinia virus expressing HIV-1 IIIB envelope
      gene products. Long-term antigen-specific CTL memory was also induced and
      maintained in distant mucosal tissues when mice were intranasally immunized with
      the recombinant influenza virus. These results indicate that mucosal immunization
      and, in particular, local vaginal immunization with recombinant influenza virus
      can provide strong, durable immune responses in the female genital tract of mice.

PMID- 14694136
TI  - High fidelity of yellow fever virus RNA polymerase.
AB  - Three consecutive plaque purifications of four chimeric yellow fever virus-dengue
      virus (ChimeriVax-DEN) vaccine candidates against dengue virus types 1 to 4 were
      performed. The genome of each candidate was sequenced by the consensus approach
      after plaque purification and additional passages in cell culture. Our data
      suggest that the nucleotide sequence error rate for SP6 RNA polymerase used in
      the in vitro transcription step to initiate virus replication was as high as 1.34
      x 10(-4) per copied nucleotide and that the error rate of the yellow fever virus
      RNA polymerase employed by the chimeras for genome replication in infected cells
      was as low as 1.9 x 10(-7) to 2.3 x 10(-7). Clustering of beneficial mutations
      that accumulated after multiple virus passages suggests that the N-terminal part
      of the prM protein, a specific site in the middle of the E protein, and the NS4B
      protein may be essential for nucleocapsid-envelope interaction during flavivirus
      assembly.

PMID- 14694135
TI  - Regulation of human immunodeficiency virus type 1 Env-mediated membrane fusion by
      viral protease activity.
AB  - We and others have presented evidence for a direct interaction between the matrix
      (MA) domain of the human immunodeficiency virus type 1 (HIV-1) Gag protein and
      the cytoplasmic tail of the transmembrane envelope (Env) glycoprotein gp41. In
      addition, it has been postulated that the MA domain of Gag undergoes a
      conformational change following Gag processing, and the cytoplasmic tail of gp41
      has been shown to modulate Env-mediated membrane fusion activity. Together, these
      results raise the possibility that the interaction between the gp41 cytoplasmic
      tail and MA is regulated by protease (PR)-mediated Gag processing, perhaps
      affecting Env function. To examine whether Gag processing affects Env-mediated
      fusion, we compared the ability of wild-type (WT) HIV-1 Env and a mutant lacking
      the gp41 cytoplasmic tail to induce fusion in the context of an active (PR(+)) or
      inactive (PR(-)) viral PR. We observed that PR(-) virions bearing WT Env
      displayed defects in cell-cell fusion. Impaired fusion did not appear to be due
      to differences in the levels of virion-associated Env, in CD4-dependent binding
      to target cells, or in the formation of the CD4-induced gp41 six-helix bundle.
      Interestingly, truncation of the gp41 cytoplasmic tail reversed the fusion
      defect. These results suggest that interactions between unprocessed Gag and the
      gp41 cytoplasmic tail suppress fusion.

PMID- 14694137
TI  - Analysis of the requirement for glycoprotein m in herpes simplex virus type 1
      morphogenesis.
AB  - A mutant of herpes simplex virus type 1 lacking both glycoprotein M and
      glycoprotein E was marginally compromised in terms of its in vitro growth
      characteristics. This finding is in marked contrast to a similar mutant of the
      related alphaherpesvirus, pseudorabies virus (A. R. Brack, J. M. Dijkstra, H.
      Granzow, B. G. Klupp, and T. C. Mettenleiter, J. Virol. 73:5364-5372, 1999), and
      suggests that the glycoprotein requirements for virion assembly may vary among
      different members of this family of viruses.

PMID- 14694139
TI  - Identification of an envelope protein from the FRD family of human endogenous
      retroviruses (HERV-FRD) conferring infectivity and functional conservation among
      simians.
AB  - A member of the HERV-W family of human endogenous retroviruses (HERV) had
      previously been demonstrated to encode a functional envelope which can form
      pseudotypes with human immunodeficiency virus type 1 virions and confer
      infectivity on the resulting retrovirus particles. Here we show that a second
      envelope protein sorted out by a systematic search for fusogenic proteins that we
      made among all the HERV coding envelope genes and belonging to the HERV-FRD
      family can also make pseudotypes and confer infectivity. We further show that the
      orthologous envelope genes that were isolated from simians-from New World monkeys
      to humans-are also functional in the infectivity assay, with one singular
      exception for the gibbon HERV-FRD gene, which is found to be fusogenic in a cell
      cell fusion assay, as observed for the other simian envelopes, but which is not
      infectious. Sequence comparison of the FRD envelopes revealed a limited number of
      mutations among simians, and one point mutation-located in the TM subunit-was
      shown to be responsible for the loss of infectivity of the gibbon envelope. The
      functional characterization of the identified envelopes is strongly indicative of
      an ancestral retrovirus infection and endogenization, with some of the envelope
      functions subsequently retained in evolution.

PMID- 14694138
TI  - Incorporation of pol into human immunodeficiency virus type 1 Gag virus-like
      particles occurs independently of the upstream Gag domain in Gag-pol.
AB  - By using particle-associated reverse transcriptase (RT) activity as an assay for
      Pol incorporation into human immunodeficiency virus type 1 (HIV-1) Gag virus-like
      particles (VLPs), it has been found that truncated, protease-negative, Gag-Pol
      missing cis Gag sequences is still incorporated into Gag VLPs, albeit at
      significantly reduced levels (10 to 20% of the level of wild-type Gag-Pol). In
      this work, we have directly measured the incorporation of truncated Gag-Pol
      species into Gag VLPs and have found that truncated Gag-Pol that is missing all
      sequences upstream of RT is still incorporated into Gag VLPs at levels
      approximating 70% of that achieved by wild-type Gag-Pol. Neither protease nor
      integrase regions in Pol are required for its incorporation, implying an
      interaction between Gag and RT sequences in the Pol protein. While the
      incorporation of Gag-Pol into Gag VLPs is reduced 12-fold by the replacement of
      the nucleocapsid within Gag with a leucine zipper motif, this mutation does not
      affect Pol incorporation. However, the deletion of p6 in Gag reduces Pol
      incorporation into Gag VLPs four- to fivefold. Pol shows the same ability as Gag
      Pol to selectively package tRNA(Lys) into Gag VLPs, and primer tRNA(3)(Lys) is
      found annealed to the viral genomic RNA. These data suggest that after the
      initial separation of Gag from Pol during cleavage of Gag-Pol by viral protease,
      the Pol species still retains the capacity to bind to both Gag and tRNA(3)(Lys),
      which may be required for Pol and tRNA(3)(Lys) to be retained in the assembling
      virion until budding is completed.

PMID- 14694140
TI  - RIII/Sa mice with a high incidence of mammary tumors express two exogenous
      strains and one potential endogenous strain of mouse mammary tumor virus.
AB  - The inbred mouse strain RIII has long been known for shedding large amounts of
      mouse mammary tumor virus (MMTV) particles in milk and for the development of
      hormone-dependent early mammary tumors at a very high incidence (>90%). We have
      established one RIII subline (RIII/Sa) that shows a pattern of virus expression
      and tumor incidence similar to that in RIII mice. In the present study, we
      analyzed the milk and mammary tumors of RIII/Sa mice for virus characterization
      by reverse transcriptase PCR (RT-PCR) cloning and sequencing of the open reading
      frame (ORF) of the MMTV long terminal repeats (LTRs). Our results show that these
      mice express a mixture of at least three different MMTV strains, two of which,
      designated here as RIII/Sa MMTV-1 and RIII/Sa MMTV-2, are exogenous. The third
      virus, RIII/Sa MMTV-3, appears to carry the signature of an endogenous provirus,
      Mtv-17. Similar studies done with the milk and mammary glands of another subline,
      RIIIS/J, revealed that they do not express MMTV in their milk. The RIII/Sa and
      RIIIS/J mice also exhibited differences in their endogenous proviral contents.
      Twelve spontaneously developed mammary tumors of RIII/Sa mice were examined for
      possible Wnt-1 and/or int-2/Fgf3 mutations that are usually found to occur in
      most mouse mammary tumors as a consequence of MMTV proviral integration. This
      work led to the isolation of one MMTV-Wnt-1 junction fragment and one MMTV-int
      2/Fgf3 junction fragment from 2 of the 12 tumors. Further analyses showed that
      both junction fragments contained the RIII/Sa MMTV-2-specific LTR ORF, indicating
      that this virus was involved in the development of both tumors. Whether RIII/Sa
      MMTV-1 and/or RIII/Sa MMTV-3 plays any role in mammary tumor development in
      RIII/Sa mice remains to be established. Overall, the present study demonstrates,
      to our surprise, that (i) RIII/Sa mice express, unlike other native mouse
      strains, three strains of MMTVs; and (ii) the virions are completely different
      from the virus expressed by another subline of RIII mice, the BR6 mice.

PMID- 14694141
TI  - Increase in endothelial cell Ca(2+) in response to mouse cremaster muscle
      contraction.
AB  - We addressed the role of endothelial cells (ECs) in metabolic dilatation of
      skeletal muscle arterioles in anaesthetized mice in situ. Electrical field
      stimulation was used to contract the cremaster muscle for 15 s at 30 Hz. Diameter
      was observed using bright field microscopy. In controls, muscle contraction
      produced a 15.7 +/- 1.5 microm dilatation from a baseline of 17.4 +/- 1.6 microm.
      Endothelial denudation (-EC) via intraluminal perfusion of air abolished this
      response (1.6 +/- 1.2 microm in -EC, P < 0.05), identifying endothelium as the
      primary vascular cell type initiating the dilatation. To investigate the role of
      EC Ca(2+) in metabolic dilatation, arteriolar ECs were loaded with Fluo-4 AM or
      BAPTA AM by intraluminal perfusion, after which blood flow was re-established.
      Ca(2+) activity of individual ECs was monitored as a function of change from
      baseline fluorescence using confocal microscopy. In ECs, whole cell Ca(2+)
      increased (>10%, P < 0.05) during muscle contraction, and localized Ca(2+)
      transients were increased (>20%, P < 0.05) during the first minute after
      contraction. Chelation of EC Ca(2+) abolished the dilatations in response to
      muscle contraction (1.1 +/- 0.7 microm, P < 0.05). Inhibition of P(1) purinergic
      receptors (with xanthine amine congener) did not alter the rate of onset of the
      dilatation (P > 0.05) but decreased its magnitude immediately post stimulation
      (7.1 +/- 0.9 microm, P < 0.05) and during recovery. These findings demonstrate
      obligatory roles for endothelium and EC Ca(2+) during metabolic dilatation in
      intact arterioles. Furthermore, they suggest that at least two separate pathways
      mediate the local response, one of which involves stimulation of endothelial P(1)
      purinergic receptors via endogenous adenosine produced during muscle activity.

PMID- 14694142
TI  - Distinctive membrane and discharge properties of rat spinal lamina I projection
      neurones in vitro.
AB  - Most lamina I neurones with a projection to the brainstem express the neurokinin
      1 receptor and thus belong to a small subgroup of lamina I neurones that are
      necessary for the development of hyperalgesia in rat models of persisting pain.
      These neurones are prone to synaptic plasticity following primary afferent
      stimulation in the noxious range while other nociceptive lamina I neurones are
      not. Here, we used whole-cell patch-clamp recordings from lamina I neurones in
      young rat spinal cord transverse slices to test if projection neurones possess
      membrane properties that set them apart from other lamina I neurones. Neurones
      with a projection to the parabrachial area or the periaqueductal grey (PAG) were
      identified by retrograde labelling with the fluorescent tracer DiI. The
      properties of lamina I projection neurones were found to be fundamentally
      different from those of unidentified, presumably propriospinal lamina I neurones.
      Two firing patterns, the gap and the bursting firing pattern, occurred almost
      exclusively in projection neurones. Most spino-parabrachial neurones showed the
      gap firing pattern while the bursting firing pattern was characteristic of spino
      PAG neurones. The underlying membrane currents had the properties of an A-type
      K(+) current and a Ca(2+) current with a low activation threshold, respectively.
      Projection neurones, especially those of the burst firing type, were more easily
      excitable than unidentified neurones and received a larger proportion of
      monosynaptic input from primary afferent C-fibres. Intracellular labelling with
      Lucifer yellow showed that projection neurones had larger somata than
      unidentified neurones and many had a considerable extension in the mediolateral
      plane.

PMID- 14694143
TI  - Isoform specificity of human Na(+), K(+)-ATPase localization and aldosterone
      regulation in mouse kidney cells.
AB  - Short-term aldosterone coordinately regulates the cell-surface expression of
      luminal epithelial sodium channels (ENaC) and of basolateral Na(+) pumps (Na(+),
      K(+)-ATPase alpha1-beta1) in aldosterone-sensitive distal nephron (ASDN) cells.
      To address the question of whether the subcellular localization of the Na(+),
      K(+)-ATPase and its regulation by aldosterone depend on subunit isoform-specific
      structures, we expressed the cardiotonic steroid-sensitive human alpha isoforms 1
      3 by retroviral transduction in mouse collecting duct mpkCCD(c14) cells. Each of
      the three exogenous human isoforms could be detected by Western blotting.
      Immunofluorescence indicated that the exogenous alpha1 subunit to a large extent
      localizes to the basolateral membrane or close to it, whereas much of the alpha2
      subunit remains intracellular. An ouabain-sensitive current carried by exogenous
      pumps could be detected in apically amphotericin B-permeabilized epithelia
      expressing human alpha1 and alpha2 subunits, but not the alpha3 subunit. This
      current displayed a higher apparent Na(+) affinity in pumps containing human
      alpha2 subunits (10 mM) than in pumps containing human alpha1 (33.2 mM) or
      endogenous (cardiotonic steroid-resistant) mouse alpha1 subunits (mean: 16.3 mM).
      A very low mRNA level of the Na(+), K(+)-ATPase gamma subunit (FXYD2) in
      mpkCCD(c14) cells suggested that this ancillary gene product is not responsible
      for the relatively low apparent Na(+) affinity measured for a1 subunit-containing
      pumps. Aldosterone increased the pump current carried by endogenous pumps and by
      pumps containing the human alpha1 subunit. In contrast, the current carried by
      pumps with a human alpha2 subunit was not stimulated by the same treatment. In
      summary, quantitative basolateral localization of the Na(+), K(+)-ATPase and its
      responsiveness to aldosterone require alpha1 subunit-specific sequences that
      differentiate this isoform from the alpha2 and alpha3 subunit isoforms.

PMID- 14694144
TI  - Slow inactivation of the Ca(V)3.1 isotype of T-type calcium channels.
AB  - T-type calcium channels (the Ca(V)3 channel family) are involved in defining the
      resting membrane potential and in neuronal activities such as oscillations and
      rebound depolarization. Their physiological roles depend upon the channel
      activation and inactivation kinetics. A fast inactivation that stops the ionic
      flux of calcium in tens of milliseconds has already been described in both native
      and heterologously expressed channels. Here, using HEK 293 cells expressing the
      rat Ca(V)3.1 channel and whole-cell voltage clamp, we investigate an additional
      inactivation process, which can be distinguished from the previously described
      fast inactivation by its slow time course of recovery from inactivation (tau= 1
      s) and by its sensitivity to external calcium. Steady-state slow inactivation is
      voltage dependent around the resting membrane potential (the potential of half
      inactivation (V(0.5)) =-70 mV, slope factor = 7.4 mV) and can reduce the calcium
      current by up to 50%. Near resting potential, the slow inactivation displays a
      half-time of induction of tens of seconds. The slow inactivation therefore
      modulates the availability of T-type calcium channels depending upon recent cell
      history, providing a mechanism to store information in a time scale of seconds.

PMID- 14694145
TI  - Inhibition of alpha-adrenergic vasoconstriction in exercising human thigh
      muscles.
AB  - The mechanisms underlying metabolic inhibition of sympathetic responses within
      exercising skeletal muscle remain incompletely understood. The aim of the present
      study was to test whether alpha(2)-adrenoreceptor-mediated vasoconstriction was
      more sensitive to metabolic inhibition than alpha(1)-vasoconstriction during
      dynamic knee-extensor exercise. We studied healthy volunteers using two
      protocols: (1) wide dose ranges of the alpha-adrenoreceptor agonists
      phenylephrine (PE, alpha(1) selective) and BHT-933 (BHT, alpha(2) selective) were
      administered intra-arterially at rest and during 27 W knee-extensor exercise (n=
      13); (2) flow-adjusted doses of PE (0.3 microg kg(-1) l(-1)) and BHT (15 microg
      kg(-1) l(-1)) were administered at rest and during ramped exercise (7 W to 37 W;
      n= 10). Ultrasound Doppler and thermodilution techniques provided direct
      measurements of femoral blood flow (FBF). PE (0.8 microg kg(-1)) and BHT (40
      microg kg(-1)) produced comparable maximal reductions in FBF at rest (-58 +/- 6
      versus-64 +/- 4%). Despite increasing the doses, PE (1.6 microg kg(-1) min(-1))
      and BHT (80 microg kg(-1) min(-1)) caused significantly smaller changes in FBF
      during 27 W exercise (-13 +/- 4 versus-3 +/- 5%). During ramped exercise,
      significant vasoconstriction at lower intensities (7 and 17 W) was seen following
      PE (-16 +/- 5 and -16 +/- 4%), but not BHT (-2 +/- 4 and -4 +/- 5%). At the
      highest intensity (37 W), FBF was not significantly changed by either drug.
      Collectively, these data demonstrate metabolic inhibition of alpha-adrenergic
      vasoconstriction in large postural muscles of healthy humans. Both alpha(1)- and
      alpha(2)-adrenoreceptor agonists produce comparable vasoconstriction in the
      resting leg, and dynamic thigh exercise attenuates alpha(1)- and alpha(2)
      mediated vasoconstriction similarly. However, alpha(2)-mediated vasoconstriction
      appears more sensitive to metabolic inhibition, because alpha(2) is completely
      inhibited even at low workloads, whereas alpha(1) becomes progressively inhibited
      with increasing workloads.

PMID- 14694146
TI  - Gender-dependent attenuation of cardiac potassium currents in type 2 diabetic
      db/db mice.
AB  - Single ventricular myocytes were prepared from control db/+ and insulin-resistant
      diabetic db/db male mice at 6 and 12 weeks of age. Peak and sustained outward
      potassium currents were measured using whole-cell voltage clamp methods. At 6
      weeks currents were fully developed in control and diabetic mice, with no
      differences in the density of either current. By 12 weeks both currents were
      significantly attenuated in the diabetic mice, but could be augmented by in vitro
      incubation with the angiotensin-converting enzyme (ACE) inhibitor quinapril (1
      microM, 5-9 h). In cells from female db/db mice (12 weeks of age), K(+) currents
      were not attenuated and no effects of quinapril were observed. To investigate
      whether lack of insulin action accounts for these gender differences, cells were
      also isolated from cardiomyocyte-specific insulin receptor knockout (CIRKO) mice.
      Both K(+) currents were significantly attenuated in cells from male and female
      CIRKO mice, and action potentials were significantly prolonged. Incubation with
      quinapril did not augment K(+) currents. Our results demonstrate that type 2
      diabetes is associated with gender-selective attenuation of K(+) currents in
      cardiomyocytes, which may underlie gender differences in the development of some
      cardiac arrhythmias. The mechanism for attenuation of K(+) currents in cells from
      male mice is due, at least in part, to an autocrine effect resulting from
      activation of a cardiac renin-angiotensin system. Insulin is not involved in
      these gender differences, since the absence of insulin action in CIRKO mice
      diminishes K(+) currents in cells from both males and females.

PMID- 14694147
TI  - Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and
      pathophysiological implications.
AB  - There is substantial evidence that oxidative stress participates in the
      pathophysiology of cardiovascular disease. Biochemical, molecular and
      pharmacological studies further implicate xanthine oxidoreductase (XOR) as a
      source of reactive oxygen species in the cardiovascular system. XOR is a member
      of the molybdoenzyme family and is best known for its catalytic role in purine
      degradation, metabolizing hypoxanthine and xanthine to uric acid with concomitant
      generation of superoxide. Gene expression of XOR is regulated by oxygen tension,
      cytokines and glucocorticoids. XOR requires molybdopterin, iron-sulphur centres,
      and FAD as cofactors and has two interconvertible forms, xanthine oxidase and
      xanthine dehydrogenase, which transfer electrons from xanthine to oxygen and
      NAD(+), respectively, yielding superoxide, hydrogen peroxide and NADH.
      Additionally, XOR can generate superoxide via NADH oxidase activity and can
      produce nitric oxide via nitrate and nitrite reductase activities. While a role
      for XOR beyond purine metabolism was first suggested in ischaemia-reperfusion
      injury, there is growing awareness that it also participates in endothelial
      dysfunction, hypertension and heart failure. Importantly, the XOR inhibitors
      allopurinol and oxypurinol attenuate dysfunction caused by XOR in these disease
      states. Attention to the broader range of XOR bioactivity in the cardiovascular
      system has prompted initiation of several randomised clinical outcome trials,
      particularly for congestive heart failure. Here we review XOR gene structure and
      regulation, protein structure, enzymology, tissue distribution and
      pathophysiological role in cardiovascular disease with an emphasis on heart
      failure.

PMID- 14694148
TI  - Rab3A negatively regulates activity-dependent modulation of exocytosis in bovine
      adrenal chromaffin cells.
AB  - Members of the Rab family of monomeric GTPases have been implicated in vesicle
      trafficking, and Rab3A, located on synaptic vesicles in neurones and secretory
      vesicles in neuroendocrine cells, is likely to be involved in vesicle fusion
      leading to neurotransmitter release. A hydrolysis-deficient mutant of Rab3A,
      Rab3AQ81L, has been shown to potently inhibit hormone release. Here we show that
      the inhibition of hormone release by Rab3AQ81L is activity-dependent. Bovine
      adrenal chromaffin cells were induced to express Rab3AQ81L and green fluorescent
      protein by adenoviral gene transfer of a bicistronic construct. Fluorescent cells
      were stimulated with single depolarizations and trains of depolarizing pulses in
      whole cell perforated patch clamp recordings, and exocytosis was detected with
      cell capacitance measurements and carbon fibre amperometry. When single
      depolarizations were used to evoke exocytosis, cells expressing Rab3AQ81L showed
      a 50% reduction in response amplitude. When trains of brief depolarizations (10
      or 40 ms) were used to evoke exocytosis, responses rapidly declined to zero in
      cells expressing Rab3AQ81L. Wild-type Rab3A had effects similar to Rab3AQ81L,
      causing significant inhibition of exocytosis only during repetitive stimulation.
      Expression of Rab5A did not alter exocytosis evoked by single depolarizations or
      repetitive stimulation. Applying a long duration depolarization in the middle of
      a stimulus train revealed that exocytotic efficacy (capacitance increase per
      amount of calcium influx) was not decreased in Rab3AQ81L-expressing cells.
      Instead, the activity-dependent increase in exocytotic efficacy observed in
      control cells did not occur in Rab3AQ81L-expressing cells. Our results suggest
      that Rab3A in the GTP bound conformation prevents activity-dependent
      facilitation.

PMID- 14694150
TI  - Effects of inflation on the coupling between the ribs and the lung in dogs.
AB  - The coupling between the ribs and the lung in dogs increases with increasing rib
      number in the cranial part of the rib cage and then decreases markedly in the
      caudal part. The hypothesis was raised that this non-uniformity is primarily
      related to differences between the areas of the lung subtended by the different
      ribs, and in the current study we tested this idea by assessing the effects of
      passive lung inflation. Thus, by causing a descent of the diaphragm, inflation
      would expand the area of the lung subtended by the caudal ribs and improve the
      coupling between these ribs and the lung. The axial displacements of the ribs and
      the changes in airway opening pressure (DeltaP(ao)) were measured in
      anaesthetized, pancuronium-treated, supine dogs while loads were applied in the
      cranial direction to individual rib pairs at functional residual capacity (FRC)
      and after passive inflation to 10 and 20 cm H(2)O transrespiratory pressure. In
      agreement with the hypothesis, inflation caused an increase in DeltaP(ao) for
      ribs 9 and 10. The most prominent alteration, however, was a marked decrease in
      DeltaP(ao) for ribs 2-8; at 20 cm H(2)O, DeltaP(ao) for these ribs was only 30%
      of the value at FRC. Additional measurements indicated that this decrease in
      DeltaP(ao) results partly from the increase in diaphragmatic compliance but
      mostly from the reduction in outward rib displacement. This alteration in the
      pattern of rib motion should add to the decrease in muscle length to reduce the
      lung expanding action of the external intercostal muscles at high lung volumes.

PMID- 14694149
TI  - Purinergic regulation of epithelial transport.
AB  - Purinergic receptors are a family of ubiquitous transmembrane receptors
      comprising two classes, P1 and P2 receptors, which are activated by adenosine and
      extracellular nucleotides (i.e. ATP, ADP, UTP and UDP), respectively. These
      receptors play a significant role in regulating ion transport in epithelial
      tissues through a variety of intracellular signalling pathways. Activation of
      these receptors is partially dependent on ATP (or UTP) release from cells and its
      subsequent metabolism, and this release can be triggered by a number of stimuli,
      often in the setting of cellular damage. The function of P2Y receptor stimulation
      is primarily via signalling through the G(q)/PLC-beta pathway and subsequent
      activation of Ca(2+)-dependent ion channels. P1 signalling is complex, with each
      of the four P1 receptors A(1), A(2A), A(2B), and A(3) having a unique role in
      different epithelial tissue types. In colonic epithelium the A(2B) receptor plays
      a prominent role in regulating Cl(-) and water secretion. In airway epithelium,
      A(2B) and A(1) receptors are implicated in the control of Cl(-) and other
      currents. In the renal tubular epithelium, A(1), A(2A), and A(3) receptors have
      all been identified as playing a role in controlling the ionic composition of the
      lumenal fluid. Here we discuss the intracellular signalling pathways for each of
      these receptors in various epithelial tissues and their roles in
      pathophysiological conditions such as cystic fibrosis.

PMID- 14694151
TI  - Membrane potential stabilization in amphibian skeletal muscle fibres in
      hypertonic solutions.
AB  - This study investigated membrane transport mechanisms influencing relative
      changes in cell volume (V) and resting membrane potential (E(m)) following
      osmotic challenge in amphibian skeletal muscle fibres. It demonstrated a
      stabilization of E(m) despite cell shrinkage, which was attributable to elevation
      of intracellular [Cl(-)] above electrochemical equilibrium through Na(+)-Cl(-)
      and Na(+)-K(+)-2Cl(-) cotransporter action following exposures to extracellular
      hypertonicity. Fibre volumes (V) determined by confocal microscope x z - scanning
      of cutaneous pectoris muscle fibres varied linearly with [1/extracellular
      osmolarity], showing insignificant volume corrections, in fibres studied in Cl(-)
      free, normal and Na(+)-free Ringer solutions and in the presence of bumetanide,
      chlorothiazide and ouabain. The observed volume changes following increases in
      extracellular tonicity were compared with microelectrode measurements of steady
      state resting potentials (E(m)). Fibres in isotonic Cl(-)-free, normal and Na(+)
      free Ringer solutions showed similar E(m) values consistent with previously
      reported permeability ratios P(Na)/P(K)(0.03-0.05) and P(Cl)/P(K) ( approximately
      2.0) and intracellular [Na(+)], [K(+)] and [Cl(-)]. Increased extracellular
      osmolarities produced hyperpolarizing shifts in E(m) in fibres studied in Cl(-)
      free Ringer solution consistent with the Goldman-Hodgkin-Katz (GHK) equation. In
      contrast, fibres exposed to hypertonic Ringer solutions of normal ionic
      composition showed no such E(m) shifts, suggesting a Cl(-)-dependent
      stabilization of membrane potential. This stabilization of E(m) was abolished by
      withdrawing extracellular Na(+) or by the combined presence of the Na(+)-Cl(-)
      cotransporter (NCC) inhibitor chlorothiazide (10 microM) and the Na(+)-K(+)-2Cl(
      ) cotransporter (NKCC) inhibitor bumetanide (10 microM), or the Na(+)-K(+)-ATPase
      inhibitor ouabain (1 or 10 microM) during alterations in extracellular
      osmolarity. Application of such agents after such increases in tonicity only
      produced a hyperpolarization after a time delay, as expected for passive Cl(-)
      equilibration. These findings suggest a model that implicates the NCC and/or NKCC
      in fluxes that maintain [Cl(-)](i) above its electrochemical equilibrium. Such
      splinting of [Cl(-)](i) in combination with the high P(Cl)/P(K) of skeletal
      muscle stabilizes E(m) despite volume changes produced by extracellular
      hypertonicity, but at the expense of a cellular capacity for regulatory volume
      increases (RVIs). In situations where P(Cl)/P(K) is low, the same co-transporters
      would instead permit RVIs but at the expense of a capacity to stabilize E(m).

PMID- 14694152
TI  - Epithelial to mesenchymal transition in renal fibrogenesis: pathologic
      significance, molecular mechanism, and therapeutic intervention.
AB  - Mature tubular epithelial cells in adult kidney can undergo epithelial-to
      mesenchymal transition (EMT), a phenotypic conversion that is fundamentally
      linked to the pathogenesis of renal interstitial fibrosis. Emerging evidence
      indicates that a large proportion of interstitial fibroblasts are actually
      originated from tubular epithelial cells via EMT in diseased kidney. Moreover,
      selective blockade of EMT in a mouse genetic model dramatically reduces fibrotic
      lesions after obstructive injury, underscoring a definite importance of EMT in
      renal fibrogenesis. Tubular EMT is proposed as an orchestrated, highly regulated
      process that consists of four key steps: (1) loss of epithelial cell adhesion;
      (2) de novo alpha-smooth muscle actin expression and actin reorganization; (3)
      disruption of tubular basement membrane; and (4) enhanced cell migration and
      invasion. Of the many factors that regulate EMT in different ways, transforming
      growth factor-beta1 is the most potent inducer that is capable of initiating and
      completing the entire EMT course, whereas hepatocyte growth factor and bone
      morphogenetic protein-7 act as EMT inhibitors both in vitro and in vivo. Multiple
      intracellular signaling pathways have been implicated in mediating EMT, in which
      Smad/integrin-linked kinase may play a central role. This article attempts to
      provide a comprehensive review of recent advances on understanding the pathologic
      significance, molecular mechanism, and therapeutic intervention of EMT in the
      setting of chronic renal fibrosis.

PMID- 14694153
TI  - Investigations of pharmacologic properties of the renal CLC-K1 chloride channel
      co-expressed with barttin by the use of 2-(p-Chlorophenoxy)propionic acid
      derivatives and other structurally unrelated chloride channels blockers.
AB  - CLC-K chloride channels are expressed in the kidney, where they play a pivotal
      role in the mechanisms of urine concentration and Na(+) reabsorption. The
      identification of barttin as an essential beta-subunit of CLC-K channels allowed
      performance of a pharmacologic characterization of wild-type CLC-K1 expressed in
      Xenopus oocytes. To this end, a series of 2-(p-chlorophenoxy)propionic acid (CPP)
      derivatives were screened using the two-microelectrode voltage-clamp technique.
      Several chemical modifications regarding the phenoxy group of the side chain
      (elimination of the oxygen atom or of methylenic groups, substitutions of the
      chlorine atom) did not alter the drug blocking activity, with five different
      derivatives showing a similar potency. Among these, a derivative of CPP carrying
      a benzyl group on the chiral center in the place of the methyl group represented
      the minimal structure for blocking CLC-K1. It inhibited the channel from the
      extracellular side with an affinity in the 150 micro M range. The blocking
      potency of this compound is fourfold increased by lowering the extracellular
      chloride concentration, suggesting that the drug interacts with the channel pore.
      Concomitantly, the effect of some "classical" Cl(-) channel blockers (9
      anthracenecarboxylic acid, 2-(phenylamino)benzoic acid, iminodibenzoic acid,
      niflumic acid, 5-nitro-2-(3-phenylpropylamino)benzoic acid, 4,4'-diisothiocyanato
      2,2'-stilbenedisulfonic acid disodium salt, and 4-acetamido-4'-isothiocyanato
      2,2'-stilbenedisulfonic acid disodium salt) was screened. 4,4'-Diisothiocyanato
      2,2'-stilbenedisulfonic acid disodium salt was the only one capable of blocking
      CLC-K1 with a potency similar to the CPP derivative, although in an irreversible
      manner. The newly identified substances provide a useful tool to investigate the
      biophysical and physiologic role of these renal channels and a starting point for
      the development of therapeutic drugs with diuretic action.

PMID- 14694154
TI  - Oncostatin M, a cytokine released by activated mononuclear cells, induces
      epithelial cell-myofibroblast transdifferentiation via Jak/Stat pathway
      activation.
AB  - Interactions between inflammatory infiltrates and resident tubular epithelial
      cells may play important roles in the development of tubulointerstitial fibrosis,
      by promoting epithelial cell-myofibroblast transdifferentiation (EMT). Human
      proximal tubular epithelial cells transdifferentiated to myofibroblasts after
      treatment with activated PBMC conditioned medium. mRNA and protein levels for
      alpha-smooth muscle actin, collagen I, and fibronectin EDA(+) (markers for the
      myofibroblastic phenotype) were increased, whereas those for E-cadherin and
      cytokeratin 19 (markers for the epithelial phenotype) were decreased. cDNA
      microarray analysis was used to identify other changes in gene expression that
      might point to novel molecular mechanisms driving EMT. Of 1176 array genes, 61
      demonstrated at least a twofold change at at least two consecutive time points,
      of the five time points examined (0.5, 4, 8, 16, and 48 h). Of these genes, 59%
      were upregulated and 41% were downregulated. The array indicated upregulation of
      expression of the oncostatin M (OSM)-specific receptor beta subunit from 4 to 48
      h after exposure of kidney epithelial cells to activated PBMC conditioned medium,
      which contained high levels of OSM. In additional experiments, it was
      demonstrated that OSM induced EMT. OSM activated the Jak/Stat signaling pathway
      in epithelial cells, and a specific inhibitor of Jak2 blocked both its
      phosphorylation after exposure to OSM and the induction of alpha-actin and loss
      of cytokeratin 19 expression. Therefore, OSM is a novel inducer of EMT and is
      likely to be one of several cytokines produced by inflammatory infiltrates that
      contribute to this and subsequent tubulointerstitial fibrosis.

PMID- 14694155
TI  - Angiotensin II type 1-receptor mediated changes in heparan sulfate proteoglycans
      in human SV40 transformed podocytes.
AB  - In patients with diabetic nephropathy, glomerular staining for heparan sulfate
      proteoglycans (HSPG) side chains and for agrin is decreased. In the present
      study, the influence of angiotensin II (AngII) on the production of HSPG in SV40
      transformed podocytes was investigated. SV40 transformed human podocytes were
      cultivated with or without 1 microM AngII, and HSPG production was measured by
      sequential DEAE-anion exchange chromatography and HPLC-DEAE separation.
      Expression of agrin was studied by indirect immunofluorescence and Western blot
      analysis using specific mono- and polyclonal antibodies. DEAE separation of total
      glycosaminoglycans (GAG) revealed a significant increase of GAG in the culture
      supernatant and decrease in the cell and matrix layer when podocytes were
      cultured for 72 h in the presence of AngII. This was particularly found for HS
      GAG. Qualitative analysis of HSPG, using gel filtration of HNO(2)-treated
      fractions, showed that AngII treatment decreased N-sulfation of HS-GAG side
      chains. Indirect immunofluorescence staining with anti-agrin polyclonal antibody
      was strongly decreased after AngII stimulation. A reduction in agrin expression
      in cell extracts could also be detected in Western blot analysis using an mAb. No
      changes in agrin mRNA were found after AngII stimulation. It is concluded from
      this study that AngII decreases the amount of HSPG on the cell surface and in the
      extracellular matrix of podocytes. Because HSPG play a fundamental role in the
      permselectivity of the glomerular basement membrane, these results thus may
      explain at least partially the antiproteinuric effects of angiotensin-converting
      enzyme inhibition in patients with diabetic nephropathy.

PMID- 14694156
TI  - The death domain of kidney ankyrin interacts with Fas and promotes Fas-mediated
      cell death in renal epithelia.
AB  - Ankyrins are a ubiquitously expressed family of conserved proteins that mediate
      the linkage of integral membrane proteins such as transporters and channels with
      the underlying cytoskeleton. Ankyrins possess a conserved death domain, the
      functional significance of which has remained puzzling. In this study, the death
      domain of AnkG190, the isoform of ankyrin expressed in kidney tubules, was used
      as bait in a yeast two-hybrid screen to identify interacting partners. One of
      these interactions was with the proapoptotic molecule Fas. This was confirmed by
      coimmunoprecipitation, colocalization, and glutathione S-transferase pull-down
      assays in cultured renal epithelial (MDCK) cells. Site-directed mutagenesis of a
      conserved arginine (R1496 in AnkG190), previously shown to be critical for the
      binding of Fas (R234 in Fas) to FADD, abolished the interaction of ankyrin's
      death domain with Fas. Overexpression of constructs containing ankyrin's death
      domain promoted Fas-mediated apoptosis in MDCK cells. The linkage between ankyrin
      and Fas was confirmed in vivo in mouse kidney tubule cells by
      coimmunoprecipitation and colocalization. In an established mouse model of renal
      ischemia-reperfusion injury characterized by apoptotic tubule cell death, the
      expression of both ankyrin and Fas was markedly induced, and the interaction
      between these molecules remained intact. The results identify a novel tethering
      interaction between ankyrin and Fas in kidney epithelia and suggest that AnkG190
      may play a role as an adapter molecule in renal tubule cell death.

PMID- 14694157
TI  - Oxidant stress leads to impaired regulation of renal cortical oxygen consumption
      by nitric oxide in the aging kidney.
AB  - Structural and functional changes occur in the kidney with aging. Previous
      studies have suggested that loss of nitric oxide production contributes to these
      changes. The authors therefore explored regulation of renal cortical oxygen
      consumption, a nitric oxide mediated effect, in tissue from Fischer 344 rats at
      different ages (4, 13, and 23 mo) to characterize changes in renal nitric oxide
      production with age. Bradykinin, enalaprilat, and amlodipine significantly
      suppressed cortical oxygen consumption in 4-mo-old rats (bradykinin: -2.5 +/-
      0.9% to -21 +/- 1.5%; enalaprilat: -0.7 +/- 0.5% to -26 +/- 1.2%; amlodipine: 
      1.3 +/- 0.9% to -18 +/- 1.2%; P < 0.05). Similar results were obtained in 13-mo
      old animals. However, in 23-mo-old animals, the responses to bradykinin and
      enalaprilat were attenuated (bradykinin: 0 +/- 0% to -13 +/- 0.9%; enalaprilat: 
      0.3 +/- 0.3% to -17 +/- 2.1%; P < 0.05), whereas the response to an NO donor was
      unaffected, suggesting decreased bioavailability of NO. Addition of the
      superoxide radical scavenger tempol restored the ability of bradykinin,
      enalaprilat, and amlodipine to suppress oxygen consumption in tissue from 23-mo
      old animals to levels seen in younger animals, suggesting NO destruction by
      superoxide as the reason for decreased NO availability. Apocynin, an inhibitor of
      NAD(P)H oxidase, similarly restored the ability of all three drugs to suppress
      oxygen consumption, suggesting NAD(P)H oxidase as the enzyme responsible for
      enhanced superoxide production in aging. Levels of eNOS protein, assessed by
      immunoblotting, did not change significantly with age. These results suggest that
      NO availability is decreased in the aging kidney and that this is due to
      scavenging of NO by superoxide produced by NAD(P)H oxidase. Oxidant stress, by
      depleting NO, may contribute to the structural and hemodynamic changes
      characteristic of the aging kidney.

PMID- 14694158
TI  - Podocytes populate cellular crescents in a murine model of inflammatory
      glomerulonephritis.
AB  - Cellular crescents are a defining histologic finding in many forms of
      inflammatory glomerulonephritis. Despite numerous studies, the origin of
      glomerular crescents remains unresolved. A genetic cell lineage-mapping study
      with a novel transgenic mouse model was performed to investigate whether visceral
      glomerular epithelial cells, termed podocytes, are precursors of cells that
      populate cellular crescents. The podocyte-specific 2.5P-Cre mouse line was
      crossed with the ROSA26 reporter line, resulting in irreversible constitutive
      expression of beta-galactosidase in doubly transgenic 2.5P-Cre/ROSA26 mice. In
      these mice, crescentic glomerulonephritis was induced with a previously described
      rabbit anti-glomerular basement membrane antiserum nephritis approach.
      Interestingly, beta-galactosidase-positive cells derived from podocytes adhered
      to the parietal basement membrane and populated glomerular crescents during the
      early phases of cellular crescent formation, accounting for at least one-fourth
      of the total cell mass. In cellular crescents, the proliferation marker Ki-67 was
      expressed in beta-galactosidase-positive and beta-galactosidase-negative cells,
      indicating that both cell types contributed to the formation of cellular
      crescents through proliferation in situ. Podocyte-specific antigens, including WT
      1, synaptopodin, nephrin, and podocin, were not expressed by any cells in
      glomerular crescents, suggesting that podocytes underwent profound phenotypic
      changes in this nephritis model.

PMID- 14694159
TI  - Heparanase is involved in the pathogenesis of proteinuria as a result of
      glomerulonephritis.
AB  - The beta-D-endoglycosidase heparanase has been proposed to be important in the
      pathogenesis of proteinuria by selectively degrading the negatively charged side
      chains of heparan sulfate proteoglycans within the glomerular basement membrane.
      A loss of negatively charged heparan sulfate proteoglycans may result in
      alteration of the permselective properties of the glomerular basement membrane,
      loss of glomerular epithelial and endothelial cell anchor points, and liberation
      of growth factors. In this study, therefore, the role of heparanase in passive
      Heymann nephritis (PHN) was examined. Normal glomeruli showed low-level
      heparanase expression as determined by immunohistochemistry and Western blot
      analysis. Days 5, 14, and 28 of PHN were associated with an increase in
      endothelial and glomerular epithelial cell heparanase. Reverse transcription-PCR
      confirmed a significant increase in mRNA at day 21 of disease (P < 0.0004).
      Furthermore, urinary and glomerular heparanase activities were significantly
      increased at days 5 and 21 of disease, respectively. Western blot analysis of
      isolated glomeruli separated into membrane- and cytosol-enriched protein
      fractions showed that the active 58-kD heparanase species was increased but
      restricted to the cytosol of diseased glomeruli at day 21. The inactive 65-kD
      precursor, however, was found in membrane and cytosol-diseased fractions,
      suggesting cell membrane processing. Complement depletion prevented glomerular
      heparanase expression; in addition, administration of a polyclonal anti
      heparanase antibody significantly reduced urinary protein excretion at day 5 of
      disease to 62 +/- 11 mg/d compared with 203 +/- 43 and 159 +/- 18 mg/d in the
      normal rabbit serum- and normal saline-treated experimental groups, respectively
      (P < 0.002). Proteinuria was reduced in the absence of any altered glomerular C5b
      9 activity, sheep IgG deposition, or rat anti-sheep antibody titers. These data
      suggest that heparanase contributes to the pathogenesis of proteinuria in PHN.

PMID- 14694160
TI  - Downregulation of Bcl-2 by podocytes is associated with progressive glomerular
      injury and clinical indices of poor renal prognosis in human IgA nephropathy.
AB  - Bcl-2 defines a new class of proto-oncogenes that block cell death without
      promoting cell proliferation. To elucidate the role of Bcl-2 in the development
      of glomerular lesions in human IgA nephropathy (IgAN), we applied
      immunohistochemistry coupled with in situ hybridization to detect the expression
      of Bcl-2 products and their association with Bax, p27(kip1), and p57(kip2) in
      modulating the apoptotic, proliferative, and sclerotic events in progressive
      glomerular injury. Glomerular cell apoptosis was examined by TdT-mediated dUTP
      biotin nick-end labeling (TUNEL) staining. A total of 51 IgAN cases were
      categorized into four subgroups (A to D) according to the severity of their
      histopathological lesions. Creatinine levels, creatinine clearance, and magnitude
      of proteinuria based on 24-h urine collections at the time of diagnostic renal
      biopsy were available for the majority of subjects. Bcl-2 expression was observed
      predominantly in podocytes in IgAN. Podocyte expression of Bcl-2 was found to be
      upregulated in early-stage disease and downregulated in late-stage disease. Bcl-2
      downregulation in progressive IgAN was associated with an increased Bax/Bcl-2
      ratio in glomerular epithelial cells and correlated with the downregulation of
      high endogenous podocyte p27(kip1) and p57(kip2) expression. Bax/Bcl-2 ratios
      positively correlated with glomerular cell apoptosis and the degree of
      glomerulosclerosis, whereas p27(kip1) and p57(kip2) expression levels were
      inversely correlated with mesangial hypercellularity and glomerulosclerosis.
      Clinicopathologic correlations demonstrated that downregulation of Bcl-2 protein
      expression was associated with indices of poor renal prognosis in human IgAN. The
      results suggest that Bcl-2 expression by podocytes may exert modulatory effects
      on cellular processes that contribute to progressive glomerular injury and play
      an important role in determining renal outcome in human IgA nephropathy.

PMID- 14694161
TI  - Activin A is a potent activator of renal interstitial fibroblasts.
AB  - The present study was conducted to examine the involvement of the activin
      follistatin system in the fibrotic process of the kidney. Immunoreactive activin
      A was upregulated in tubular cells in the kidneys with unilateral ureteral
      obstruction but not in normal and contralateral kidneys. Activin A promoted cell
      proliferation, enhanced the expression of type I collagen mRNA, and induced the
      production of alpha-smooth muscle actin in a rat kidney fibroblast cell line (NRK
      49F cells) as well as in primary cultured renal interstitial fibroblasts. In
      contrast, activin A did not affect the expressions of alpha-smooth muscle actin
      and type I collagen in renal epithelial tubular cell lines LLC-PK1, and MDCK.
      Follistatin, an antagonist of activin A, significantly inhibited cell
      proliferation in NRK-49F cells. Blockade of activin signaling by overexpression
      of truncated type II activin receptor, which lacked the intracellular kinase
      domain, decreased cell proliferation and reduced the expression level of type I
      collagen mRNA in NRK-49F cells. The expression of activin A was induced by TGF
      beta 1 or activin A itself. Induction of type I collagen expression by TGF-beta 1
      was reduced by follistatin or by overexpression of truncated type II activin
      receptor. These results suggest that activin A produced by tubular cells acts as
      a paracrine factor that activates renal interstitial fibroblasts during the
      fibrotic processes of the kidney.

PMID- 14694162
TI  - A1 adenosine receptor activation inhibits inflammation, necrosis, and apoptosis
      after renal ischemia-reperfusion injury in mice.
AB  - It was previously demonstrated that preischemic A(1) adenosine receptor (AR)
      activation protects renal function after ischemia-reperfusion (IR) injury in
      rats. The role of the A(1) AR in modulating inflammation, necrosis, and apoptosis
      in the kidney after IR renal injury was further characterized. C57BL/6 mice were
      subjected to 30 min of renal ischemia, with or without pretreatment with 1,3
      dipropyl-8-cyclopentylxanthine or 2- chlorocyclopentyladenosine (selective A(1)
      AR antagonist and agonist, respectively). Plasma creatinine levels and renal
      inflammation, necrosis, and apoptosis were compared 24 h after renal injury.
      C57BL/6 mice that had been pretreated with the A(1) AR agonist demonstrated
      significantly improved renal function and reduced expression of inflammatory
      markers, necrosis, and apoptosis 24 h after IR injury. In contrast, C57BL/6 mice
      that had been pretreated with the A(1) AR antagonist demonstrated significantly
      worsened renal function and increased expression of inflammatory markers,
      necrosis, and apoptosis. In conclusion, it was demonstrated that endogenous and
      exogenous preischemic activation of the A(1) AR protects against IR injury in
      vivo, through mechanisms that reduce inflammation, necrosis, and apoptosis.

PMID- 14694163
TI  - Prevention of acute ischemic renal failure by targeted delivery of growth factors
      to the proximal tubule in transgenic mice: the efficacy of parathyroid hormone
      related protein and hepatocyte growth factor.
AB  - Treatment of acute renal failure (ARF) would be enhanced by identification of
      factors that accelerate renal recovery from injury. Parathyroid hormone-related
      protein (PTHrP) and hepatocyte growth factor (HGF) have been shown to stimulate
      proliferation in proximal nephron-derived cells. For studying the
      pathophysiologic roles and therapeutic potential of these two factors in ARF,
      transgenic mice overexpressing PTHrP or HGF in the proximal tubule under the
      direction of the gamma-glutamyl transpeptidase-I promoter were developed. These
      mice display (1) abundant expression of the respective transgenes in the kidney;
      (2) similar PTH type I receptor and HGF receptor (c-met) expression levels in the
      proximal tubule compared with control littermates; and (3) normal renal
      morphology, function, and tubule cell proliferation under basal conditions.
      However, in contrast to control mice, when acute ischemic renal injury was
      induced, renal function rapidly and dramatically recovered in HGF-overexpressing
      mice. In addition, 48 h after ischemia, HGF-overexpressing transgenic mice
      displayed a fourfold increase in tubule cell proliferation and a threefold
      decrease in apoptotic tubule cell death compared with control mice. In contrast,
      PTHrP-overexpressing mice responded to either ischemic or folic acid-induced
      renal damage similarly to control mice. These studies demonstrate that
      overexpression of PTHrP in the proximal nephron of mice does not seem to provide
      protection against acute renal injury. In marked contrast, HGF overexpression
      results in dramatic protection from ischemia-induced ARF, without inducing any
      apparent alteration in the physiology of the kidney under normal conditions.
      These studies suggest that HGF, when targeted specifically to the proximal
      tubule, may have therapeutic potential in providing protection against ischemia
      induced renal failure.

PMID- 14694164
TI  - Glycosaminoglycans enhance the trifluoroethanol-induced extension of beta 2
      microglobulin-related amyloid fibrils at a neutral pH.
AB  - beta(2)-Microglobulin-related (A beta 2M) amyloidosis is a frequent and serious
      complication in patients on long-term dialysis, and beta(2)-microglobulin is a
      major structural component of A beta 2M amyloid fibrils. Several biologic
      molecules inhibiting the depolymerization of A beta 2M amyloid fibrils at a
      neutral pH were found recently. The effect of trifluoroethanol and
      glycosaminoglycans (GAG) on the extension of the fibrils at a neutral pH was
      investigated with the use of fluorescence spectroscopy with thioflavin T,
      circular dichroism spectroscopy, and electron microscopy. Trifluoroethanol at
      concentrations of up to 20% (vol/vol) caused fibril extension of heparin
      stabilized seeds, inducing a subtle change in the tertiary structure of beta(2)
      microglobulin and stabilizing the fibrils at a neutral pH. This extension
      reaction followed a first-order kinetic model. In addition, some GAG, especially
      heparin, dose-dependently enhanced the fibril extension. These results suggest
      that some GAG, especially heparin, may bind to the fibrils and enhance their
      deposition in vivo. Thus, the experimental system described here should be useful
      to search for the factors that accelerate A beta 2M amyloid deposition in vivo.
      In addition, the interference of the binding of GAG to A beta 2M amyloid fibrils
      may be an attractive therapeutic modality.

PMID- 14694165
TI  - Transplant renal artery stenosis.
AB  - Transplant renal artery stenosis (TRAS) is a recognized, potentially curable
      cause of posttransplant arterial hypertension, allograft dysfunction, and graft
      loss. It usually occurs 3 mo to 2 yr after transplantation, but early or later
      presentations are not uncommon. The prevalence ranges widely from 1 to 23% in
      different series, reflecting the heterogeneous criteria used to establish the
      diagnosis, the different manner of preservation of the graft, and surgical
      expertise. Reported cases are progressively increasing in parallel with the use
      of non-invasive investigation procedures, such as Doppler ultrasonography and
      magnetic resonance (MR) angiography, that arouse the suspicion of the disease
      even in less symptomatic cases. However, definitive diagnosis of hemodynamically
      significant stenosis rests on the use of invasive angiographic techniques.
      Percutaneous transluminal angioplasty (PTA) is the treatment of choice and
      restores kidney perfusion in 60 to 90% of cases. The risk of re-stenosis, the
      major drawback of the procedure, is prevented by the use of expandable
      endoprostheses. Surgery is indicated for stenoses that cannot be treated by PTA
      or that recur after it. Doppler ultrasonography is the procedure of choice to
      evaluate graft perfusion before and after revascularization.

PMID- 14694166
TI  - Timing of complications in percutaneous renal biopsy.
AB  - Percutaneous renal biopsy (PRB) is a safe and effective tool in the diagnosis and
      management of renal disease; however, the optimal timing of observation after
      biopsy is not clearly established. With the use of real-time ultrasound guidance,
      PRB of native kidneys was performed in 750 adult patients at an academic
      institution by an attending nephrologist or fellow between June 1983 and June
      2002. All patients were observed for 23 to 24 h after biopsy for the presence,
      severity, and timing of complications. Biopsy-related complications occurred in
      98 (13%) patients; minor complications occurred in 50 (6.6%) patients, and major
      complications occurred in 48 (6.4%) patients. One (0.1%) patient died as a result
      of the biopsy. Multivariate analysis using logistic regression found only serum
      creatinine at baseline predictive of a complication. Patients with a serum
      creatinine > or = 5.0 mg/dl were 2.3 times as likely to have a complication (odds
      ratio, 2.3; 95% confidence interval, 1.3 to 4.1; P < 0.005). Complications were
      identified in 38 (42%) patients by < or = 4 h, in 61 (67%) patients by < or = 8
      h, in 77 (85%) patients by < or = 12 h, and in 81 (89%) patients at < or = 24 h.
      The PRB remains a safe procedure, but the risk of complication is higher in
      patients with advanced renal insufficiency. After biopsy, an observation time of
      up to 24 h remains optimal as an observation period of < or = 8 h risks missing >
      or = 33% of complications.

PMID- 14694167
TI  - Effects of early and late intervention with epoetin alpha on left ventricular
      mass among patients with chronic kidney disease (stage 3 or 4): results of a
      randomized clinical trial.
AB  - It is not known whether prevention of anemia among patients with chronic kidney
      disease would affect the development or progression of left ventricular (LV)
      hypertrophy. A randomized controlled trial was performed with 155 patients with
      chronic kidney disease (creatinine clearance, 15 to 50 ml/min), with entry
      hemoglobin concentrations ([Hb]) of 110 to 120 g/L (female patients) or 110 to
      130 g/L (male patients). Patients were monitored for 2 yr or until they required
      dialysis; the patients were randomized to receive epoetin alpha as necessary to
      maintain [Hb] between 120 and 130 g/L (group A) or between 90 and 100 g/L (group
      B). [Hb] increased for group A (from 112 +/- 9 to 121 +/- 14 g/L, mean +/- SD)
      and decreased for group B (from 112 +/- 8 to 108 +/- 13 g/L) (P < 0.001, group A
      versus group B). On an intent-to-treat analysis, the changes in LV mass index for
      the groups during the 2-yr period were not significantly different (2.5 +/- 20
      g/m(2) for group A versus 4.5 +/- 20 g/m(2) for group B, P = NS). There was no
      significant difference between the groups in 2-yr mean unadjusted systolic BP
      (141 +/- 14 versus 138 +/- 13 mmHg) or diastolic BP (80 +/- 6 versus 79 +/- 7
      mmHg). The decline in renal function in 2 yr, as assessed with nuclear
      estimations of GFR, also did not differ significantly between the groups (8 +/- 9
      versus 6 +/- 8 ml/min per 1.73 m(2)). In conclusion, maintenance of [Hb] above
      120 g/L, compared with 90 to 100 g/L, had similar effects on the LV mass index
      and did not clearly affect the development or progression of LV hypertrophy. The
      maintenance of [Hb] above 100 g/L for many patients in group B might have been
      attributable to the relative preservation of renal function.

PMID- 14694168
TI  - Corticosteroid effectiveness in IgA nephropathy: long-term results of a
      randomized, controlled trial.
AB  - Proteinuria plays a causal role in the progression of IgA nephropathy (IgAN). A
      previous controlled trial showed that steroids are effective in reducing
      proteinuria and preserving renal function in patients with IgAN. The objective of
      this study was to evaluate the long-term effectiveness of steroids in IgAN,
      examine the trend of proteinuria during follow-up (starting from the hypothesis
      that the degree of reduction in proteinuria may influence IgAN outcome), and
      evaluate how histologic scores can influence steroid response. A secondary
      analysis of a multicenter, randomized, controlled trial of 86 adult IgAN patients
      who were receiving supportive therapy or intravenous methylprednisolone plus oral
      prednisone for 6 mo was conducted. Ten-year renal survival was significantly
      better in the steroid than in the control group (97% versus 53%; log rank test P
      = 0.0003). In the 72 patients who did not reach the end point (doubling in
      baseline serum creatinine), median proteinuria significantly decreased (1.9 g/24
      h at baseline, 1.1 g/24 h after 6 mo, and 0.6 g/24 h after a median of 7 yr). In
      the 14 progressive patients, proteinuria increased from a median of 1.7 g/24 h at
      baseline to 2.0 g/24 h after 6 mo and 3.3 g/24 h after a median of 5 yr. Steroids
      were effective in every histologic class. Cox multivariate regression analyses
      showed that, in addition to steroids, a low baseline histologic score, a
      reduction in proteinuria after 6 mo, and no increase in proteinuria during follow
      up all were independent predictors of a beneficial outcome. Steroids
      significantly reduce proteinuria and protect against renal function deterioration
      in IgAN. The histologic picture and proteinuria during early and late follow-up
      improve the prediction of outcome, but considerable variability remains outside
      the model.

PMID- 14694169
TI  - Clinical and molecular analysis of patients with renal hypouricemia in Japan
      influence of URAT1 gene on urinary urate excretion.
AB  - Renal hypouricemia is an inherited and heterogeneous disorder characterized by
      increased urate clearance (CUA). The authors recently established that urate was
      reabsorbed via URAT1 on the tubular apical membrane and that mutations in
      SLC22A12 encoding URAT1 cause renal hypouricemia. This study was undertaken to
      elucidate and correlate clinical and genetic features of renal hypouricemia. The
      SLC22A12 gene was sequenced in 32 unrelated idiopathic renal hypouricemia
      patients, and the relationships of serum urate levels, and CUA/creatinine
      clearance (Ccr) to SLC22A12 genotype were examined. Uricosuric (probenecid and
      benzbromarone) and anti-uricosuric drug (pyrazinamide) loading tests were also
      performed in some patients. Three patients had exercise-induced acute renal
      failure (9.4%), and four patients had urolithiasis (12.5%). The authors
      identified eight new mutations and two previously reported mutations that result
      in loss of function. Thirty patients had SLC22A12 mutations; 24 homozygotes and
      compound heterozygotes, and 6 heterozygotes. Mutation G774A dominated SLC22A12
      mutations (74.1% in 54 alleles). Serum urate levels were significantly lower and
      CUA/Ccr was significantly higher in heterozygotes compared with healthy subjects;
      these changes were even more significant in homozygotes and compound
      heterozygotes. These CUA/Ccr relations demonstrated a gene dosage effect that
      corresponds with the difference in serum urate levels. In contrast to healthy
      subjects, the CUA/Ccr of patients with homozygous and compound heterozygous
      SLC22A12 mutations was unaffected by pyrazinamide, benzbromarone, and probenecid.
      The findings indicate that SLC22A12 was responsible for most renal hypouricemia
      and that URAT1 is the primary reabsorptive urate transporter, targeted by
      pyrazinamide, benzbromarone, and probenecid in vivo.

PMID- 14694170
TI  - Hemoglobin levels and erythropoietin doses in hemodialysis and peritoneal
      dialysis patients in the United States.
AB  - Erythropoietic agents, a cornerstone of management, are a major component of the
      cost of renal replacement therapy. The objectives of this study were to compare
      (on a month-by-month basis) U.S. hemodialysis and peritoneal dialysis patients in
      terms of the proportion of patients receiving erythropoietin, erythropoietin
      doses, and hemoglobin levels after initiation of erythropoietin. Patients studied
      (hemodialysis, n = 121,970; peritoneal dialysis, n = 7129) began dialysis between
      1995 and 2000, had Medicare as their primary payer, were 65 yr old or older at
      dialysis inception, had no erythropoietin claims before dialysis inception, and
      did not have a switch in dialysis modality in the first 6 mo of dialysis therapy.
      Total monthly erythropoietin doses and average monthly hemoglobin levels were
      calculated from Medicare claims. The proportion of patients who received
      erythropoietin plateaued at 3 mo in both groups: 25% in peritoneal dialysis
      patients and 80% in hemodialysis patients. However, monthly erythropoietin doses
      plateaued at 30,000 units in peritoneal dialysis patients and 60,000 units in
      hemodialysis patients, a disparity not explicable by differences in baseline
      characteristics. Among subjects who received erythropoietin, mean hemoglobin
      levels were similar at steady state in both populations and met the National
      Kidney Foundation Dialysis Outcomes Quality Initiative hemoglobin target level of
      11 to 12 g/dl. Hemoglobin levels in U.S. hemodialysis and peritoneal populations
      are similar. However, erythropoietin doses are dramatically higher in
      hemodialysis patients.

PMID- 14694171
TI  - Absence of association between organic solvent exposure and risk of chronic renal
      failure: a nationwide population-based case-control study.
AB  - Exposure to organic solvents has been suggested to cause or exacerbate renal
      disease, but methodologic concerns regarding previous studies preclude firm
      conclusions. We examined the role of organic solvents in a population-based case
      control study of early-stage chronic renal failure (CRF). All native Swedish
      residents aged 18 to 74 yr, living in Sweden between May 1996 and May 1998,
      formed the source population. Incident cases of CRF in a pre-uremic stage (n =
      926) and control subjects (n = 998), randomly selected from the study base,
      underwent personal interviews that included a detailed occupational history.
      Expert rating by a certified occupational hygienist was used to assess organic
      solvent exposure intensity and duration. Relative risks were estimated by odds
      ratios (OR) in logistic regression models, with adjustment for potentially
      important covariates. The overall risk for CRF among subjects ever exposed to
      organic solvents was virtually identical to that among never-exposed (OR, 1.01;
      95% confidence interval [CI], 0.81 to 1.25). No dose-response relationships were
      observed for lifetime cumulative solvent exposure, average dose, or exposure
      frequency or duration. The absence of association pertained to all subgroups of
      CRF: glomerulonephritis (OR, 0.96; 95% CI, 0.68 to 1.34), diabetic nephropathy
      (OR, 1.02; 95% CI, 0.74 to 1.41), renal vascular disease (OR, 1.16; 95% CI, 0.76
      to 1.75), and other renal CRF (OR, 0.92; 95% CI, 0.66 to 1.27). The results from
      a nationwide, population-based study do not support the hypothesis of an adverse
      effect of organic solvents on CRF development, in general. Detrimental effects
      from subclasses of solvents or on specific renal diseases cannot be ruled out.

PMID- 14694172
TI  - Blood pressure and the survival of renal allografts from living donors.
AB  - Levels of BP have been associated with increasing rates of renal allograft
      failure from cadaveric donors, independent of renal function. The effect of BP, a
      modifiable risk factor, on the failure rates of renal allografts from living
      donors is unknown and maybe obscured by the rate of decline of renal function
      from this source of organs. A nonconcurrent cohort study collecting data from 392
      recipients of a renal allograft from a living donor during 1990 to 2001 was
      performed. Multivariable Cox regression models were fit by means of time-varying
      terms for systolic BP (SBP), diastolic BP (DBP), mean arterial BP (MAP), pulse
      pressure, and renal function during the first year after transplantation to study
      the association of BP and the time to allograft failure. Potential nonlinear
      relationships were considered by fractional polynomial terms. Recipient gender,
      preemptive transplantation, and time-varying terms for the natural logarithm of
      creatinine clearance and acute rejection were retained in the multivariable
      model. Including separate multivariable models with nonlinear terms for SBP (P =
      0.02), for DBP (P = 0.02), or for MAP (P = 0.05) during the first year
      significantly improved the fit of the respective models and confirmed that there
      is an association of BP and allograft failure independent of renal function.
      Pulse pressure had neither a linear nor nonlinear association with allograft
      failure. In this nonconcurrent study, the level of BP during the first year
      affected the survival of renal allografts from living donors, independent of
      renal function. Further investigation is required to confirm the level of BP that
      is optimal to prevent foreshortened duration of survival.

PMID- 14694173
TI  - Factors that affect postdialysis rebound in serum urea concentration, including
      the rate of dialysis: results from the HEMO Study.
AB  - Previous studies have suggested that postdialysis urea rebound is related to K/V,
      the rate of dialysis, but a systematic analysis of factors that affect rebound
      has not been reported. With the use of 30-min and, in a subset, 60-min
      postdialysis samples, postdialysis urea rebound was measured to (1) determine how
      well previously proposed equations based on the rate of dialysis (K/V) predict
      rebound in a large sample of patients with varying characteristics, (2) determine
      whether other factors besides K/V affect rebound, and (3) estimate more precise
      values for coefficients in prediction equations for rebound. Rebound was
      calculated relative to both immediate and 20-s postdialysis samples to study
      early components of rebound unrelated to access recirculation. The equilibrated
      Kt/V (eKt/V) computed by fitting the two-pool variable volume model to the 30-min
      postdialysis sample agreed well with eKt/V based on the 60-min postdialysis
      sample. Using the pre-, post-, and 30-min postdialysis samples for 1245 patients
      with arteriovenous (AV) accesses, the median intercompartmental mass transfer
      coefficient (Kc) was 797 ml/min for rebound computed relative to the 20-s
      postdialysis samples and 592 ml/min relative to the immediate postdialysis
      samples. K/V was the strongest predictor of rebound among 22 factors considered.
      Other factors associated with greater rebound for 1331 patients using AV accesses
      or venous catheters included access type, black race, male gender, absence of
      congestive heart failure, greater age, ultrafiltration rate, and low predialysis
      or intradialysis systolic BP. Equations of the form eKt/V = single-pool Kt/V - B
      x (K/V) were fit to the data. With AV access, the optimum values for the slope
      term (B) were 0.39 and 0.46 (in h(-1)) for single-pool Kt/V calculated based on
      20-s postdialysis or immediate postdialysis samples, respectively. For patients
      using venous catheters, the respective values for B were 0.22 and 0.29.
      Postdialysis urea rebound can be predicted with acceptable accuracy from a
      postdialysis sample using a zero-intercept, K/V-based rate equation. Several
      patient or treatment-specific factors predict enhanced or reduced rebound. Rate
      equation slope coefficients for K/V of 0.39 (AV access) and 0.22 (venous access)
      are proposed when a 15- to 20-s slow-flow method is used to draw the postdialysis
      blood. Slightly higher K/V slope coefficients (0.46 and 0.29, respectively)
      should be used if a shorter (e.g., 10 s) slow-flow period is used.

PMID- 14694174
TI  - Cardiovascular comorbidity and late referral impact arteriovenous fistula
      survival: a prospective multicenter study.
AB  - Autologous arteriovenous fistulas (AVF) have the best 5-yr patency and the lowest
      complication rate among hemodialysis vascular accesses. However, maturation
      requirements to optimize survival are unknown. A longitudinal cohort study was
      conducted to ascertain risk factors for failure, maturation time, and survival of
      the first AVF. All patients who initiated hemodialysis between January 1, 1997,
      and December 31, 2002, in three centers were included in this study. Analysis was
      restricted to patients who received an AVF. Cox regression was used to estimate
      the association between predictors of interest and primary and secondary AVF
      survival. Of the 535 patients enrolled (mean age, 66.5 yr; 57.8% male; 26.7%
      diabetic), 513 (96%) received an AVF. Patients who initiated with catheters (47%)
      cannulated their AVF earlier (median maturation period, 0.78 versus 1.80 mo; P <
      0.001). Median primary and secondary survivals were longer than 50 and 72 mo,
      respectively. After adjustment for confounding factors, cardiovascular disease
      (hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.26 to 2.67),
      utilization earlier than 1 mo after placement (HR, 1.94; 95% CI, 1.34 to 2.82),
      and referral within 3 mo of dialysis start (HR, 1.55; 95% CI, 1.04 to 2.32) were
      associated with a reduction in primary AVF survival. Presence of cardiovascular
      disease (HR, 2.21; 95% CI, 1.38 to 3.55), maturation time <15 d (HR, 2.12; 95%
      CI, 1.20 to 3.73), and presence of catheters at hemodialysis initiation (HR,
      1.79; 95% CI, 1.13 to 2.84) were associated with lower secondary AVF survival. It
      is concluded that cardiovascular disease, late referral, temporary catheters, and
      early cannulation are associated with impaired AVF survival. It is recommended
      that AVF be allowed to mature at least 1 mo before cannulation.

PMID- 14694175
TI  - Frequency of patient-physician contact and patient outcomes in hemodialysis care.
AB  - There is little evidence supporting the widespread belief that regular patient
      physician contact in chronic disease management leads to better patient outcomes.
      The objective of this study was to examine the relationship of the frequency of
      patient-physician contact with several patient outcomes in a prospective cohort
      study begun in 1995 of incident hemodialysis patients treated at 75 US dialysis
      clinics. Average frequency of patient-physician contact at each clinic was
      determined by clinic survey (low, monthly or less frequent; intermediate, between
      monthly and weekly; high, more than weekly). The authors used logistic, Poisson,
      and Cox proportional hazards regression analyses to assess the relationship
      between contact and satisfaction, quality of life, patient adherence,
      hospitalizations, and mortality. Of 735 hemodialysis patients, 14.3% were treated
      at clinics with high frequency of contact, 65.2% intermediate, and 20.5% low.
      Patients treated at clinics reporting less frequent physician contact had lower
      odds of rating the frequency at which they saw a nephrologist excellent (low:
      adjusted OR = 0.39, 95% CI, 0.23-0.67; intermediate: adjusted OR = 0.57, 95% CI,
      0.37-0.87; reference, high) and greater odds of nonadherence (low: adjusted OR =
      2.89, 95% CI, 1.01-8.29; intermediate: adjusted OR = 1.58, 95% CI, 0.78-3.19).
      However, patient survival did not vary by frequency of physician contact (low:
      adjusted RH = 0.87, 95% CI, 0.53-1.44; intermediate: adjusted RH = 1.33, 95% CI,
      0.82-2.13), nor did patients' overall ratings of care, hospitalization rates, or
      quality of life measures. Although less frequent patient-physician contact was
      associated with lower patient satisfaction with that contact and patient
      nonadherence, it was not associated with several other outcomes of care. Future
      studies are needed to assess the individual frequency and nature of physician
      contact over time, including total time spent with the patient and quality of the
      interaction, to guide the provision of patient-centered and cost-effective care.

PMID- 14694177
TI  - Addition of sirolimus to cyclosporine delays the recovery from delayed graft
      function but does not affect 1-year graft function.
AB  - Delayed graft function (DGF) has long been identified as one of the main
      correlates of poor graft survival in cadaveric renal transplantation, but the
      factors that affect its onset and duration are not fully elucidated. The impact
      of two immunosuppressive protocols on the incidence and length of DGF among
      kidney transplant recipients of a suboptimal organ was evaluated. Patients were
      randomly treated with corticosteroids (CS); low-dose cyclosporine (CsA) and
      sirolimus (SRL; group 1; n = 42); or CS, full-dose CsA, and mycophenolate mofetil
      (group 2; n = 48). All recipients received immunoprophylaxis with basiliximab.
      After 3 mo, group 1 discontinued CsA and continued with SRL, whereas group 2
      continued the same treatment. The incidence of DGF was similar in the two groups
      (group 1 = 52.4%; group 2 = 58.3%), whereas its duration was significantly higher
      in the group 1 (19.0 +/- 6.0 versus 10.3 +/- 3.2 d; P = 0.001). Both groups
      showed 100% actuarial graft and patient survival at 1-yr. Among DGF patients,
      serum creatinine (sCr) at discharge was significantly worse in group 1 (sCr, 3.0
      +/- 1.0 versus 1.5 +/- 0.2 mg/dl; calculated creatinine clearance, 31.2 +/- 9.3
      versus 61.1 +/- 10 ml/min; P = 0.001). During the first year, the former group
      displayed a significant improvement of graft function, such that at 1-yr, no
      difference could be measured between groups (sCr, 1.8 +/- 0.5 versus 1.7 +/- 0.4
      mg/dl; calculated creatinine clearance, 51.5 +/- 10.2 versus 53.3 +/- 9.4
      ml/min). In conclusion, in de novo renal transplanted patients, the
      administration of SRL, in combination with low-dose CsA, is associated with a
      delayed recovery from DGF but does not worsen 1-yr graft function.

PMID- 14694176
TI  - Proteomic-based detection of urine proteins associated with acute renal allograft
      rejection.
AB  - At present, the diagnosis of renal allograft rejection requires a renal biopsy.
      Clinical management of renal transplant patients would be improved by the
      development of non-invasive markers of rejection that can be measured frequently.
      This study sought to determine whether such candidate proteins can be detected in
      urine using mass spectrometry. Four patient groups were rigidly defined on the
      basis of allograft function, clinical course, and allograft biopsy result: acute
      clinical rejection group (n = 18), stable transplant group (n = 22), acute
      tubular necrosis group (n = 5), and recurrent (or de novo) glomerulopathy group
      (n = 5). Urines collected the day of the allograft biopsy were analyzed by mass
      spectrometry. As a normal control group, 28 urines from healthy individuals were
      analyzed the identical manner, as well as 5 urines from non-transplanted patients
      with lower urinary tract infection. Furthermore, sequential urine analysis was
      performed in patients in the acute clinical rejection and the stable transplant
      group. Three prominent peak clusters were found in 17 of 18 patients (94%) with
      acute rejection episodes, but only in 4 of 22 patients (18%) without clinical and
      histologic evidence for rejection and in 0 of 28 normal controls (P < 0.001). In
      addition, the presence or absence of these peak clusters correlated with the
      clinicopathologic course in most patients. Acute tubular necrosis,
      glomerulopathies, lower urinary tract infection, and cytomegalovirus viremia were
      not confounding variables. In conclusion, proteomic technology together with
      stringent definition of patient groups can detect urine proteins associated with
      acute renal allograft rejection. Identification of these proteins may prove
      useful as non-invasive diagnostic markers for rejection and the development of
      novel therapeutic agents.

PMID- 14694178
TI  - Diets for patients with chronic kidney disease, still worth prescribing.

PMID- 14694179
TI  - Frequency of physician visits to patients on in-center maintenance hemodialysis:
      does one strategy fit all?

PMID- 14694181
TI  - Macrophage activation and Fcgamma receptor-mediated signaling do not require
      expression of the SLP-76 and SLP-65 adaptors.
AB  - The Src-homology 2 domain-containing, leukocyte-specific phosphoprotein of 76 kDa
      (SLP-76) is a hematopoietic adaptor that plays a central role during
      immunoreceptor-mediated activation of T lymphocytes and mast cells and collagen
      receptor-induced activation of platelets. Despite similar levels of expression in
      macrophages, SLP-76 is not required for Fc receptor for immunoglobulin G (IgG;
      FcgammaR)-mediated activation. We hypothesized that the related adaptor SLP-65,
      which is also expressed in macrophages, may compensate for the loss of SLP-76
      during FcgammaR-mediated signaling and functional events. To address this
      hypothesis, we examined bone marrow-derived macrophages (BMM) from wild-type (WT)
      mice or mice lacking both of these adaptors. Contrary to our expectations, SLP
      76(-/-) SLP-65(-/-) BMM demonstrated normal FcgammaR-mediated activation,
      including internalization of Ig-coated sheep red blood cells and production of
      reactive oxygen intermediates. FcgammaR-induced biochemical events were normal in
      SLP-76(-/-) SLP-65(-/-) BMM, including phosphorylation of phospholipase C and the
      extracellular signaling-regulated kinases 1 and 2. To determine whether
      macrophages functioned normally in vivo, we infected WT and SLP-76(-/-) SLP-65(-/
      ) mice with sublethal doses of Listeria monocytogenes (LM), a bacterium against
      which the initial host defense is provided by activated macrophages. WT and SLP
      76(-/-) SLP-65(-/-) mice survived acute, low-dose infection and showed no
      difference in the number of liver or spleen LM colony-forming units, a measure of
      the total body burden of this organism. Taken together, these data suggest that
      neither SLP-76 nor SLP-65 is required during FcgammaR-dependent signaling and
      functional events in macrophages.

PMID- 14694182
TI  - Mouse bone marrow contains large numbers of functionally competent neutrophils.
AB  - The mouse has become an important model for immunological studies including
      innate immunity. Creating transgenic mice offers unique possibilities to study
      gene-function relationships. However, relatively little is known about the
      physiology of neutrophils from wild-type mice. Do they behave like human
      neutrophils, or are there species-specific differences that need to be considered
      when extrapolating results from mice to humans? How do we isolate neutrophils
      from mice? For practical reasons, many studies on mouse neutrophils are done with
      bone marrow cells. However, human bone marrow neutrophils appear to be
      heterogeneous and functionally immature. We have isolated and compared
      neutrophils from mouse bone marrow and from peripheral blood obtained by tail
      bleeding. Using the same Percoll density gradient for both preparations, we have
      obtained morphologically mature neutrophils from bone marrow and blood. Both cell
      populations responded to formylmethionyl-leucyl-phenylalanine (fMLF) with primary
      and secondary granule release and superoxide production. Quantitative analysis of
      our data revealed minor differences between cells from bone marrow and blood.
      Superoxide production and primary granule release were stimulated at lower fMLF
      concentrations in blood neutrophils. However, the amplitude and the kinetics of
      maximal responses were similar. The principal difference was the lifespan of the
      two cell populations. Bone marrow cells survived significantly longer in culture,
      which may suggest that they are receiving antiapoptic signals that are absent in
      the blood. Our data suggest that mice have a large reservoir of functionally
      competent neutrophils in their bone marrow. This reservoir may be needed to
      replace circulating neutrophils rapidly during infection.

PMID- 14694183
TI  - p38 activation through Toll-like receptors modulates IFN-gamma-induced expression
      of the Tap-1 gene only in macrophages.
AB  - Although interferon-gamma (IFN-gamma) induces the transporter associated with
      antigen processing (Tap)-1 expression in macrophages, cooperation with
      lipopolysaccharide signaling through Toll-like receptor 4 (TLR4) accelerates the
      kinetics and increases the overall levels of this gene. In this report, we show
      that peptidoglycan signaling through TLR2 and bacterial CpG DNA signaling through
      TLR9 are functionally equivalent at synergizing with IFN-gamma in regulating Tap
      1 expression in macrophages. Activation of the p38 mitogen-activated protein
      kinase is necessary for this response, which correlates with increased
      phosphorylation of signal transducer and activator of transcription-1 on serine
      727. Activation of p38, however, is not sufficient, as this signaling event does
      not affect the response to IFN-gamma in HeLa cells. The cooperation between these
      different signaling pathways also requires membrane fluidity. These data suggest
      that macrophages possess an ability to coordinate the signaling between the IFN
      gamma and TLR receptors.

PMID- 14694184
TI  - Monocyte cytokine production during pregnancy.

PMID- 14694185
TI  - End-stage differentiation of neutrophil granulocytes in vivo is accompanied by up
      regulation of p27kip1 and down-regulation of CDK2, CDK4, and CDK6.
AB  - The in vivo expression profiles of cell-cycle proteins regulating G1-to-S-phase
      transition were determined in three neutrophil precursor populations from human
      bone marrow: myeloblasts (MBs) and promyelocytes (PMs); myelocytes (MCs) and
      metamyelocytes (MMs); and band cells (BCs) and segmented neutrophil cells (SCs)
      and in mature polymorphonuclear neutrophils (PMNs) from peripheral blood.
      Complete cell-cycle arrest was observed in BCs/SCs and PMNs. Cyclins D1, D2, and
      D3 were found to be down-regulated during granulopoiesis, whereas a slight
      increase of cyclin E was seen. In contrast, cyclin-dependent kinase (CDK)2, -4,
      and -6 were down-regulated from the MC/MM stages and onward. The transcript
      levels of CDK2, -4, and -6 were concurrently down-regulated. As the only CDK
      inhibitor, p27kip1 protein and mRNA expression were up-regulated in MCs/MMs and
      reached peak levels in PMNs. Protein expression of retinoblastoma protein and the
      related pocket proteins p107 and p130 was down-regulated from the MC/MM stages
      and onward. This is the first report to describe expression levels of cell-cycle
      proteins during granulopoiesis in vivo, and it strongly contrasts the
      observations made in cell-culture systems in vitro.

PMID- 14694186
TI  - 4-1BB-dependent inhibition of immunosuppression by activated CD4+CD25+ T cells.
AB  - 4-1BB (CD137) is a costimulatory molecule involved in the activation and survival
      of CD4, CD8, and natural killer cells. Although a great deal has been learned as
      to how 4-1BB-mediated signaling governs the immunity of conventional T cells, the
      functional role of 4-1BB in the context of CD4(+)CD25(+) regulatory T cell (Tr)
      activation is largely unknown. Using 4-1BB-intact and -deficient mice, we
      investigated the effect of the 4-1BB/4-1BB ligand pathway on the suppressive
      function of Tr cells. Our data indicate that although 4-1BB is expressed on Tr
      cells, its contribution to their proliferation is minimal. We also showed that
      signaling through the 4-1BB receptor inhibited the suppressive function of Tr
      cells in vitro and in vivo. It is interesting that anti-4-1BB-mediated but not
      anti-GITR-directed inhibition was more potent when Tr cells were preactivated.
      Collectively, these data indicate that 4-1BB signaling is critical in Tr cell
      immunity.

PMID- 14694187
TI  - Are SOCS suppressors, regulators, and degraders?
AB  - Suppressors of cytokine signaling have been identified as inhibitors of cytokine
      signaling and have been shown to act in a classical feedback loop. The prototype
      members of this family, cytokine-inducible Src homology 2-containing protein and
      suppressors of cytokine signaling SOC was cloned as cytokine-inducible immediate
      early gene that could inhibit the activation of signal transducer and activator
      of transcription factors and block biological responses to several cytokines.
      Although steady progress has been made in the identification of SOCS and their
      physiological importance, precisely how SOCS proteins function has not yet been
      discovered. Many recent findings indicate that the SOCS act as adaptors that
      regulate the turnover of certain substrates by interacting with and activating an
      E3 ubiquitin ligase. Here, I explore recent evidence (presented at the
      International Cytokine Society meeting in Dublin, Ireland, September 2003) that
      SOCS molecules may not act simply as regulators of cytokine responses but may
      also play an essential role in determining cell fate and controlling cell
      differentiation.

PMID- 14694189
TI  - Specificity determinants and diversification of the Brassica self-incompatibility
      pollen ligand.
AB  - Self-incompatibility in crucifers is effected by allele-specific interactions
      between the highly polymorphic stigmatic S locus receptor kinase (SRK) and its
      pollen ligand, the S locus cysteine-rich protein (SCR). Here we show that
      specificity in SCR function is determined by four contiguous amino acids in one
      variant, indicating that the minimum sequence requirement for gaining a new
      specificity can be low. We also provide evidence for an extraordinarily high
      degree of evolutionary flexibility in SCR, whereby SCR can tolerate extensive
      amino acid changes within the limits of maintaining the same predicted overall
      structure. This remarkable adaptability suggests a hypothesis for generation of
      new self-incompatibility specificities by gradual modification of SRK-SCR
      affinities and, more generally, for functional specialization within families of
      homologous ligands and receptors.

PMID- 14694190
TI  - Adult male rat hippocampus synthesizes estradiol from pregnenolone by cytochromes
      P45017alpha and P450 aromatase localized in neurons.
AB  - In adult mammalian brain, occurrence of the synthesis of estradiol from
      endogenous cholesterol has been doubted because of the inability to detect
      dehydroepiandrosterone synthase, P45017alpha. In adult male rat hippocampal
      formation, significant localization was demonstrated for both cytochromes
      P45017alpha and P450 aromatase, in pyramidal neurons in the CA1-CA3 regions, as
      well as in the granule cells in the dentate gyrus, by means of
      immunohistochemical staining of slices. Only a weak immunoreaction of these P450s
      was observed in astrocytes and oligodendrocytes. ImmunoGold electron microscopy
      revealed that P45017alpha and P450 aromatase were localized in pre- and
      postsynaptic compartments as well as in the endoplasmic reticulum in principal
      neurons. The expression of these cytochromes was further verified by using
      Western blot analysis and RT-PCR. Stimulation of hippocampal neurons with N
      methyl-d-aspartate induced a significant net production of estradiol. Analysis of
      radioactive metabolites demonstrated the conversion from [(3)H]pregnenolone to
      [(3)H]estradiol through dehydroepiandrosterone and testosterone. This activity
      was abolished by the application of specific inhibitors of cytochrome P450s.
      Interestingly, estradiol was not significantly converted to other steroid
      metabolites. Taken together with our previous finding of a P450scc-containing
      neuronal system for pregnenolone synthesis, these results imply that 17beta
      estradiol is synthesized by P45017alpha and P450 aromatase localized in
      hippocampal neurons from endogenous cholesterol. This synthesis may be regulated
      by a glutamate-mediated synaptic communication that evokes Ca(2+) signals.

PMID- 14694191
TI  - Learning rules and network repair in spike-timing-based computation networks.
AB  - Plasticity in connections between neurons allows learning and adaptation, but it
      also allows noise to degrade the function of a network. Ongoing network self
      repair is thus necessary. We describe a method to derive spike-timing-dependent
      plasticity rules for self-repair, based on the firing patterns of a functioning
      network. These plasticity rules for self-repair also provide the basis for
      unsupervised learning of new tasks. The particular plasticity rule derived for a
      network depends on the network and task. Here, self-repair is illustrated for a
      model of the mammalian olfactory system in which the computational task is that
      of odor recognition. In this olfactory example, the derived rule has qualitative
      similarity with experimental results seen in spike-timing-dependent plasticity.
      Unsupervised learning of new tasks by using the derived self-repair rule is
      demonstrated by learning to recognize new odors.

PMID- 14694192
TI  - Protein topology determines binding mechanism.
AB  - Protein recognition and binding, which result in either transient or long-lived
      complexes, play a fundamental role in many biological functions, but sometimes
      also result in pathologic aggregates. We use a simplified simulation model to
      survey a range of systems where two highly flexible protein chains form a
      homodimer. In all cases, this model, which corresponds to a perfectly funneled
      energy landscape for folding and binding, reproduces the macroscopic experimental
      observations on whether folding and binding are coupled in one step or whether
      intermediates occur. Owing to the minimal frustration principle, we find that, as
      in the case of protein folding, the native topology is the major factor that
      governs the choice of binding mechanism. Even when the monomer is stable on its
      own, binding sometimes occurs fastest through unfolded intermediates, thus
      showing the speedup envisioned in the fly-casting scenario for molecular
      recognition.

PMID- 14694193
TI  - Magnetism in dense hexagonal iron.
AB  - The magnetic state of hexagonal close-packed iron has been the subject of debate
      for more than three decades. Although Mossbauer measurements find no evidence of
      the hyperfine splitting that can signal the presence of magnetic moments, density
      functional theory predicts an antiferromagnetic (afm) ground state. This
      discrepancy between theory and experiment is now particularly important because
      of recent experimental findings of anomalous splitting in the Raman spectra and
      the presence of superconductivity in hexagonal close-packed iron, which may be
      caused by magnetic correlations. Here, we report results from first principles
      calculations on the previously predicted theoretical collinear afm ground state
      that strongly support the presence of afm correlations in hexagonal close-packed
      iron. We show that anomalous splitting of the Raman mode can be explained by spin
      phonon interactions. Moreover, we find that the calculated hyperfine field is
      very weak and would lead to hyperfine splitting below the resolution of Mossbauer
      experiments.

PMID- 14694194
TI  - The crystal structure of Pseudomonas avirulence protein AvrPphB: a papain-like
      fold with a distinct substrate-binding site.
AB  - AvrPphB is an avirulence (Avr) protein from the plant pathogen Pseudomonas
      syringae that can trigger a disease-resistance response in a number of host
      plants including Arabidopsis. AvrPphB belongs to a novel family of cysteine
      proteases with the charter member of this family being the Yersinia effector
      protein YopT. AvrPphB has a very stringent substrate specificity, catalyzing a
      single proteolytic cleavage in the Arabidopsis serine/threonine kinase PBS1. We
      have determined the crystal structure of AvrPphB by x-ray crystallography at 1.35
      A resolution. The structure is composed of a central antiparallel beta-sheet,
      with alpha-helices packing on both sides of the sheet to form a two-lobe
      structure. The core of this structure resembles the papain-like cysteine
      proteases. The similarity includes the AvrPphB active site catalytic triad of Cys
      98, His-212, and Asp-227 and the oxyanion hole residue Asn-93. Based on analogy
      with inhibitor complexes of the papain-like proteases, we propose a model for the
      substrate-binding mechanism of AvrPphB. A deep and positively charged pocket (S2)
      and a neighboring shallow surface (S3) likely bind to aspartic acid and glycine
      residues in the substrate located two (P2) and three (P3) residues N terminal to
      the cleavage site, respectively. Further implications about the specificity of
      plant pathogen recognition are also discussed.

PMID- 14694195
TI  - Thymic selection can compensate for mutations affecting T cell activation and
      generate a normal T cell repertoire in mutant mice.
AB  - Thymic selection adjusts the reactivity of the peripheral T cell repertoire to
      maximize recognition of pathogens and minimize stimulation by innocuous
      substances and self-antigen. The study of molecules implicated in T cell
      activation often involves the generation of knockout (-/-) mice. In many
      instances, knockout animals display revealing phenotypes. But should a lack of
      phenotype be interpreted as a lack of function? Bcl-xgamma was shown previously
      to affect T cell activation in vitro, and here we note that overexpression of
      this molecule increases cell cycling after T cell receptor ligation by antibody.
      It was therefore surprising that Bcl-xgamma(-/-), Bcl-xgamma transgenic, and WT T
      cells displayed similar levels of sensitivity to antigen according to ex vivo
      stimulation. Bcl-xgamma could be demonstrated to influence competitiveness and
      selection of thymocytes in a manner that counteracted the effects of Bcl-xgamma
      mutation on T cell activation. These findings suggest that thymic selection can
      overcome genetic defects in T cell activation to generate a T cell repertoire of
      normal reactivity.

PMID- 14694196
TI  - A site-specific factor interacts directly with its cognate RNA editing site in
      chloroplast transcripts.
AB  - RNA editing involves a variety of genetic systems and occurs by different
      mechanisms. In higher plant chloroplasts, specific sites of some transcripts are
      subject to C-to-U conversion. We have previously shown that site-specific trans
      acting factors for psbE and petB mRNA editing bind corresponding cis-elements,
      which are located 5 nucleotides upstream from the editing site. Here we report
      that, by using mRNAs labeled either at the center of the upstream cis-element or
      at the editing site, the site-specific factors can be cross-linked with
      nucleotides at both positions. Mutations of nucleotides in the proximal region of
      the editing site revealed a correlation between editing activity and cross
      linking efficiency of factors with the editing site, even though cross-linking
      with the upstream cis-element was unaffected. These observations suggest that the
      site-specific factor binds stably to the upstream ciselement, whereas it
      interacts weakly with the editing site. This finding raises the intriguing
      possibility that the site-specific factor is involved in both site-determination
      and C-to-U conversion in chloroplast RNA editing.

PMID- 14694197
TI  - A Plasmodium falciparum candidate vaccine based on a six-antigen polyprotein
      encoded by recombinant poxviruses.
AB  - To generate broadly protective T cell responses more similar to those acquired
      after vaccination with radiation-attenuated Plasmodium falciparum sporozoites, we
      have constructed candidate subunit malaria vaccines expressing six
      preerythrocytic antigens linked together to produce a 3240-aa-long polyprotein
      (L3SEPTL). This polyprotein was expressed by a plasmid DNA vaccine vector (DNA)
      and by two attenuated poxvirus vectors, modified vaccinia virus Ankara (MVA) and
      fowlpox virus of the FP9 strain. MVAL3SEPTL boosted anti-thrombospondin-related
      adhesive protein (anti-TRAP) and anti-liver stage antigen 1 (anti-LSA1) CD8(+) T
      cell responses when primed by single antigen TRAP- or LSA1-expressing DNAs,
      respectively, but not by DNA-L3SEPTL. However, prime boost regimes involving two
      heterologous viral vectors expressing L3SEPTL induced a strong cellular response
      directed against an LSA1 peptide located in the C-terminal region of the
      polyprotein. Peptide-specific T cells secreted IFN-gamma and were cytotoxic. IFN
      gamma-secreting T cells specific for each of the six antigens were induced after
      vaccination with L3SEPTL, supporting the use of polyprotein inserts to induce
      multispecific T cells against P. falciparum. The use of polyprotein constructs in
      nonreplicating poxviruses should broaden the target antigen range of vaccine
      induced immunity and increase the number of potential epitopes available for
      immunogenetically diverse human populations.

PMID- 14694198
TI  - The C-type lectin SIGN-R1 mediates uptake of the capsular polysaccharide of
      Streptococcus pneumoniae in the marginal zone of mouse spleen.
AB  - SIGN-R1, a recently discovered C-type lectin expressed at high levels on
      macrophages within the marginal zone of the spleen, mediates the uptake of
      dextran polysaccharides by these phagocytes. We now find that encapsulated
      Streptococcus pneumoniae are rapidly cleared by these macrophages from the
      bloodstream, and that capture also takes place when different cell lines express
      SIGN-R1 after transfection. To assess the role of the capsular polysaccharide of
      S. pneumoniae (CPS) in the interaction of SIGN-R1 with pneumococci, we first
      studied binding and uptake of serotype 14 CPS in transfected cells. Binding was
      observed and was of a much higher avidity (3000-fold) for CPS 14 than dextran.
      The CPSs from four different serotypes were also cleared by marginal zone
      macrophages in vivo. To establish a role for SIGN-R1 in this uptake, we
      selectively down-regulated expression of the lectin by pretreatment of the mice
      with SIGN-R1 antibodies, including a newly generated hamster monoclonal called
      22D1. For several days after this transient knockout, the marginal zone
      macrophages were unable to take up either CPSs or dextrans. Therefore, marginal
      zone macrophages in mice have a receptor that interacts with capsular
      pneumococcal polysaccharides, setting the stage for further studies of the
      functional consequences of this interaction.

PMID- 14694199
TI  - Differentiation stage-specific activation of p38 mitogen-activated protein kinase
      isoforms in primary human erythroid cells.
AB  - p38alpha, p38beta, p38gamma, and p38delta are four isoforms of p38 mitogen
      activated protein (MAP) kinase (MAPK) involved in multiple cellular functions
      such as cell proliferation, differentiation, apoptosis, and inflammation
      response. In the present study, we examined the mRNA expression pattern of each
      of the four isoforms during erythroid differentiation of primary erythroid
      progenitors. We show that p38alpha and p38gamma transcripts are expressed in
      early hematopoietic progenitors as well as in late differentiating erythroblasts,
      whereas p38delta mRNA is only expressed and active during the terminal phase of
      erythroid differentiation. On the other hand, p38beta is minimally expressed in
      early CD34(+) hematopoietic progenitors but not expressed in lineage-committed
      erythroid progenitors. We also determined the phosphorylation/activation of
      p38alpha, MAPK kinase 3/6, and MAPKAP-2 in response to erythropoietin and stem
      cell factor. We found that phosphorylation of p38alpha, MAPK kinase kinase 3/6
      and MAPKAP-2 occurs only upon growth factor withdrawal in primary erythroid
      progenitors. Moreover, our data indicate that activation of p38alpha does not
      induce apoptosis or promote proliferation of erythroid progenitors. On the other
      hand, under steady-state culture conditions, both p38alpha and p38delta isoforms
      are increasingly phosphorylated activated in the terminal phase of
      differentiation. This increased phosphorylation/activity was accompanied by up
      regulation of heat shock protein 27 phosphorylation. Finally, we demonstrate that
      tumor necrosis factor alpha, an inflammatory cytokine that is modulated by
      p38alpha, is expressed by differentiating erythroblasts and inhibition of
      p38alpha or tumor necrosis factor alpha results in reduction in differentiation.
      Taken together, our data demonstrate that both p38alpha and delta isoforms
      function to promote the late-stage differentiation of primary erythroid
      progenitors and are likely to be involved in functions related to erythrocyte
      membrane remodeling and enucleation.

PMID- 14694200
TI  - Motor training compensates for cerebellar dysfunctions caused by oligodendrocyte
      ablation.
AB  - The role played by oligodendrocytes (OLs), the myelinating cells of the CNS,
      during brain development has not been fully explored. We have addressed this
      question by inducing a temporal and reversible ablation of OLs on postnatal CNS
      development. OL ablation in newborn mice leads to a profound alteration in the
      structure of the cerebellar cortex, which can be progressively rescued by newly
      generated cells, leading to a delayed myelination. Nevertheless, the temporal
      shift of the OL proliferation and myelinating program cannot completely
      compensate for developmental defects, resulting in impaired motor functions in
      the adult. Strikingly, we show that, despite these abnormalities, epigenetic
      factors, such as motor training, are able to fully rescue cerebellar-directed
      motor skills.

PMID- 14694201
TI  - A human complement receptor 1 polymorphism that reduces Plasmodium falciparum
      rosetting confers protection against severe malaria.
AB  - Parasitized red blood cells (RBCs) from children suffering from severe malaria
      often adhere to complement receptor 1 (CR1) on uninfected RBCs to form clumps of
      cells known as "rosettes." Despite a well documented association between
      rosetting and severe malaria, it is controversial whether rosetting is a cause or
      a correlate of parasite virulence. CR1-deficient RBC show greatly reduced
      rosetting; therefore, we hypothesized that, if rosetting is a direct cause of
      malaria pathology, CR1-deficient individuals should be protected against severe
      disease. In this study, we show that RBC CR1 deficiency occurs in up to 80% of
      healthy individuals from the malaria-endemic regions of Papua New Guinea. This
      RBC CR1 deficiency is associated with polymorphisms in the CR1 gene and,
      unexpectedly, with alpha-thalassemia, a common genetic disorder in Melanesian
      populations. Analysis of a case-control study demonstrated that the CR1
      polymorphisms and alpha-thalassemia independently confer protection against
      severe malaria. We have therefore identified CR1 as a new malaria resistance gene
      and provided compelling evidence that rosetting is an important parasite
      virulence phenotype that should be a target for drug and vaccine development.

PMID- 14694202
TI  - Transcriptome-based determination of multiple transcription regulator activities
      in Escherichia coli by using network component analysis.
AB  - Cells adjust gene expression profiles in response to environmental and
      physiological changes through a series of signal transduction pathways. Upon
      activation or deactivation, the terminal regulators bind to or dissociate from
      DNA, respectively, and modulate transcriptional activities on particular
      promoters. Traditionally, individual reporter genes have been used to detect the
      activity of the transcription factors. This approach works well for simple, non
      overlapping transcription pathways. For complex transcriptional networks, more
      sophisticated tools are required to deconvolute the contribution of each
      regulator. Here, we demonstrate the utility of network component analysis in
      determining multiple transcription factor activities based on transcriptome
      profiles and available connectivity information regarding network connectivity.
      We used Escherichia coli carbon source transition from glucose to acetate as a
      model system. Key results from this analysis were either consistent with
      physiology or verified by using independent measurements.

PMID- 14694203
TI  - Structure of HrcQB-C, a conserved component of the bacterial type III secretion
      systems.
AB  - Type III secretion systems enable plant and animal bacterial pathogens to deliver
      virulence proteins into the cytosol of eukaryotic host cells, causing a broad
      spectrum of diseases including bacteremia, septicemia, typhoid fever, and bubonic
      plague in mammals, and localized lesions, systemic wilting, and blights in
      plants. In addition, type III secretion systems are also required for biogenesis
      of the bacterial flagellum. The HrcQ(B) protein, a component of the secretion
      apparatus of Pseudomonas syringae with homologues in all type III systems, has a
      variable N-terminal and a conserved C-terminal domain (HrcQ(B)-C). Here, we
      report the crystal structure of HrcQ(B)-C and show that this domain retains the
      ability of the full-length protein to interact with other type III components. A
      3D analysis of sequence conservation patterns reveals two clusters of residues
      potentially involved in protein-protein interactions. Based on the analogies
      between HrcQ(B) and its flagellum homologues, we propose that HrcQ(B)-C
      participates in the formation of a C-ring-like assembly.

PMID- 14694205
TI  - Overexpression of membrane-associated fatty acid binding protein (FABPpm) in vivo
      increases fatty acid sarcolemmal transport and metabolism.
AB  - Fatty acid translocase (FAT/CD36) is a key fatty acid transporter in skeletal
      muscle. However, the effects on fatty acid transport by another putative fatty
      acid transporter, plasma membrane-associated fatty acid binding protein (FABPpm),
      have not been determined in mammalian tissue. We examined the functional effects
      of overexpressing FABPpm on the rates of 1) palmitate transport across the
      sarcolemma and 2) palmitate metabolism in skeletal muscle. One muscle (soleus)
      was transfected with pTracer containing FABPpm cDNA. The contralateral muscle
      served as control. After injecting the FABPpm cDNA, muscles were electroporated.
      FABPpm overexpression was directly related to the quantity of DNA administered.
      Electrotransfection (200 microg/muscle) rapidly induced FABPpm protein
      overexpression (day 1, +92%, P < 0.05), which was further increased during the
      next few days (days 3-7; range +142% to +160%, P < 0.05). Sarcolemmal FABPpm was
      comparably increased (day 7, +173%, P < 0.05). Neither FAT/CD36 expression nor
      sarcolemmal FAT/CD36 content was altered. FABPpm overexpression increased the
      rates of palmitate transport (+79%, P < 0.05). Rates of palmitate incorporation
      into phospholipids were also increased +36%, as were the rates of palmitate
      oxidation (+20%). Rates of palmitate incorporation into triacylglycerol depots
      were not altered. These studies demonstrate that in mammalian tissue FABPpm
      overexpression increased the rates of palmitate transport across the sarcolemma,
      an effect that is independent of any changes in FAT/CD36. However, since the
      overexpression of plasmalemmal FABPpm (+173%) exceeded the effects on the rates
      of palmitate transport and metabolism, it appears that the overexpression of
      FABPpm alone is not sufficient to induce completely parallel increments in
      palmitate transport and metabolism. This suggests that other mechanisms are
      required to realize the full potential offered by FABPpm overexpression.

PMID- 14694204
TI  - Dissociation of transactivation from transrepression by a selective
      glucocorticoid receptor agonist leads to separation of therapeutic effects from
      side effects.
AB  - Glucocorticoids (GCs) are the most commonly used antiinflammatory and
      immunosuppressive drugs. Their outstanding therapeutic effects, however, are
      often accompanied by severe and sometimes irreversible side effects. For this
      reason, one goal of research in the GC field is the development of new drugs,
      which show a reduced side-effect profile while maintaining the antiinflammatory
      and immunosuppressive properties of classical GCs. GCs affect gene expression by
      both transactivation and transrepression mechanisms. The antiinflammatory effects
      are mediated to a major extent via transrepression, while many side effects are
      due to transactivation. Our aim has been to identify ligands of the GC receptor
      (GR), which preferentially induce transrepression with little or no
      transactivating activity. Here we describe a nonsteroidal selective GR-agonist,
      ZK 216348, which shows a significant dissociation between transrepression and
      transactivation both in vitro and in vivo. In a murine model of skin
      inflammation, ZK 216348 showed antiinflammatory activity comparable to
      prednisolone for both systemic and topical application. A markedly superior side
      effect profile was found with regard to increases in blood glucose, spleen
      involution, and, to a lesser extent, skin atrophy; however, adrenocorticotropic
      hormone suppression was similar for both compounds. Based on these findings, ZK
      216348 should have a lower risk, e.g., for induction of diabetes mellitus. The
      selective GR agonists therefore represent a promising previously undescribed
      class of drug candidates with an improved therapeutic index compared to classical
      GCs. Moreover, they are useful tool compounds for further investigating the
      mechanisms of GR-mediated effects.

PMID- 14694206
TI  - Human uncoupling protein-3 and obesity: an update.
AB  - The cloning of the uncoupling protein (UCP)1 homologs UCP2 and UCP3 has raised
      considerable interest in the mechanism. The expression of UCP3 mainly in skeletal
      muscle mitochondria and the potency of the skeletal muscle as a thermogenic organ
      made UCP3 an attractive target for studies toward manipulation of energy
      expenditure to fight disorders such as obesity and type 2 diabetes.
      Overexpressing UCP3 in mice resulted in lean, hyperphagic mice. However, the lack
      of an apparent phenotype in mice lacking UCP3 triggered the search for
      alternative functions of UCP3. The observation that fatty acid levels
      significantly affect UCP3 expression has given UCP3 a position in fatty acid
      handling and/or oxidation. Emerging data indicate that the primary physiological
      role of UCP3 may be the mitochondrial handling of fatty acids rather than the
      regulation of energy expenditure through thermogenesis. It has been proposed that
      UCP3 functions to export fatty acid anions away from the mitochondrial matrix. In
      doing so, fatty acids are exchanged with protons, explaining the uncoupling
      activity of UCP3. The exported fatty acid anions may originate from hydrolysis of
      fatty acid esters by a mitochondrial thioesterase, or they may have entered the
      mitochondria as nonesterified fatty acids by incorporating into and flip-flopping
      across the mitochondrial inner membrane. Regardless of the origin of the fatty
      acid anions, this putative function of UCP3 might be of great importance in
      protecting mitochondria against fatty acid accumulation and may help to maintain
      muscular fat oxidative capacity.

PMID- 14694207
TI  - Evidence for genetic factors underlying the insulin resistance syndrome in
      american indians.
AB  - Previous analyses of American Indians of the Strong Heart Study have demonstrated
      that various insulin-resistance variables cluster, although knowledge about the
      genetic determination of these clusters is unknown. In an effort to explore the
      influences on the aggregation of insulin-resistance phenotypes, we used principal
      component factor analysis to examine the clustering of these phenotypes in
      participants of the Strong Heart Family Study and evaluated the genetic and
      environmental contributions of such factors. Nine traits were chosen for
      principal component factor analysis: BMI, diastolic blood pressure, fasting
      glucose, high-density lipoprotein-cholesterol, natural log-transformed insulin,
      natural log-transformed triglycerides, percentage of body fat, systolic blood
      pressure, and waist-to-hip ratio. Analyses revealed three clusters:
      glucose/insulin/obesity, blood pressure, and dyslipidemia factors. Using a
      variance component approach and accounting for the effects of age, sex, center,
      and medication, we detected significant heritabilities (h2) for the three
      factors: h2 = 0.67, h2 = 0.33, and h2 = 0.61, respectively. In multivariate
      analysis, no significant genetic correlations among factors were found. These
      results suggest that heredity explains a substantial proportion of the
      variability of the factors that underlie the insulin resistance syndrome in
      American Indians and that these factors are genetically independent.

PMID- 14694208
TI  - Effects of different dietary fat types on postprandial appetite and energy
      expenditure.
AB  - OBJECTIVE: Observational studies suggest that monounsaturated (MUFA) and trans
      fatty acids (TRANS) are more fattening than polyunsaturated fatty acids (PUFA).
      Therefore, the aim of this study was to investigate the acute effect of intake of
      PUFA, MUFA, or TRANS on appetite and energy expenditure (EE). RESEARCH METHODS
      AND PROCEDURES: Three test meals were randomly given in a cross-over design to 19
      overweight (BMI: 26.8 +/- 0.4 kg/m2), young (25.2 +/- 0.7 years) men. The fat
      rich breakfasts (0.8 g fat/kg body weight, 60% energy from fat) varied only in
      the source of C:18-fat. EE was measured continuously in a respiration chamber,
      and appetite sensations were rated by visual analog scales before and every 30
      minutes, for 5 hours, after the meal. After 5 hours, an ad libitum meal was
      served, and energy intake was registered. Sensory evaluations of all meals were
      given using visual analog scales. Data were analyzed by two-way ANOVA. RESULTS:
      There were no differences in basal or postprandial values of appetite ratings and
      EE, in subsequent ad libitum energy intake, or in the sensory evaluation of the
      test meals among the 3 test days. DISCUSSION: Giving acutely large amounts of
      MUFA, PUFA, or TRANS did not impose any differences in appetite and EE in
      overweight humans. However, studies with extended protocols and other subject
      groups are warranted to investigate the long-term effect of dietary fat quality
      on the regulation of energy balance and body weight.

PMID- 14694209
TI  - Gastric pacing for morbid obesity: plasma levels of gastrointestinal peptides and
      leptin.
AB  - OBJECTIVE: A gastric pacemaker has been developed to treat morbid obesity.
      Patients experience increased satiety, the ability to reduce food intake, and a
      resultant weight loss. However, the mechanism behind the changed eating behavior
      in paced patients is still under investigation. RESEARCH METHODS AND PROCEDURES:
      This study was performed on 11 morbidly obese patients (mean BMI, 46.0 kg/m2)
      treated with gastric pacing. The peripheral blood levels of satiety signals of
      cholecystokinin (CCK), somatostatin, glucagon-like peptide-1 (GLP-1), and leptin
      were studied 1 month before gastric pacer implantation, 1 month after
      implantation, and 6 months after activation of electrical stimulation. Blood
      samples were drawn 12 hours after fasting and in response to a hypocaloric meal
      (270 kcal). Patients were followed monthly for vital signs and weight level.
      RESULTS: Gastric pacing resulted in a significant weight loss of a mean of 10.4
      kg (4.4 BMI units). No negative side effects or complications were observed
      during the treatment. After activation of the pacemaker, meal-related response of
      CCK and somatostatin and basal levels of GLP-1 and leptin were significantly
      reduced (p < 0.05) compared with the tests before gastric pacing. The weight loss
      correlated significantly with a decrease of leptin levels (R = 0.79, p < 0.01).
      DISCUSSION: Gastric pacing is a novel and promising therapy for morbid obesity.
      Activation of the gastric pacer was associated with a decrease in plasma levels
      of CCK, somatostatin, GLP-1, and leptin. More studies are necessary to elucidate
      the correlations between satiety, weight loss, and digestive neuro-hormone
      changes.

PMID- 14694210
TI  - Leptin expression in hypothalamic PVN reverses dietary obesity and
      hyperinsulinemia but stimulates ghrelin.
AB  - OBJECTIVE: In order to circumvent the multiple peripheral effects of
      hyperleptinemia and leptin resistance, the efficacy of leptin transgene
      expression in the hypothalamic paraventricular nucleus (PVN) to reinstate the
      central energy homeostasis in obesity was examined. RESEARCH METHODS AND
      PROCEDURES: A recombinant adeno-associated viral vector encoding either leptin
      (rAAV-lep) or green fluorescent protein (rAAV-GFP) was microinjected into the PVN
      of obesity-prone rats consuming a high-fat diet (HFD). RESULTS: rAAV-lep, and not
      rAAV-GFP, microinjection significantly reduced energy intake and enhanced energy
      expenditure, thereby resulting in normalization of weight and blood levels of
      leptin, insulin, free fatty acids, and glucose concomitant with enhanced ghrelin
      secretion during the extended period of observation. DISCUSSION: Thus, we show,
      for the first time, that amelioration of leptin insufficiency with enhanced
      localized leptin availability in the PVN alone can reverse dietary obesity and
      the attendant hyperinsulinemia and concurrently block the central stimulatory
      effects of elevated endogenous ghrelin on food intake and adiposity.

PMID- 14694211
TI  - Dietary regulation of fat oxidative gene expression in different skeletal muscle
      fiber types.
AB  - OBJECTIVE: To determine the effect of a high-fat diet on the expression of genes
      important for fat oxidation, the protein abundance of the transcription factors
      peroxisome proliferator-activated receptor (PPAR) isoforms alpha and gamma, and
      selected enzyme activities in type I and II skeletal muscle. RESEARCH METHODS AND
      PROCEDURES: Sprague-Dawley rats consumed either a high-fat (HF: 78% energy, n =
      8) or high-carbohydrate (64% energy, n = 8) diet for 8 weeks while remaining
      sedentary. RESULTS: The expression of genes important for fat oxidation tended to
      increase in both type I (soleus) and type II (extensor digitorum longus) fiber
      types after an HF dietary intervention. However, the expression of muscle type
      carnitine palmitoyltransferase I was not increased in extensor digitorum longus.
      Analysis of the gene expression of both peroxisome proliferator-activated
      receptor-gamma coactivator and fork-head transcription factor O1 demonstrated no
      alteration in response to the HF diet. Similarly, PPARalpha and PPARgamma protein
      levels were also not altered by the HF diet. DISCUSSION: An HF diet increased the
      expression of an array of genes involved in lipid metabolism, with only subtle
      differences evident in the response within differing skeletal muscle fiber types.
      Despite changes in gene expression, there were no effects of diet on peroxisome
      proliferator-activated receptor-gamma coactivator and fork-head transcription
      factor O1 mRNA and the protein abundance of PPARalpha and PPARgamma.

PMID- 14694212
TI  - Central adiposity determines prevalence differences of the metabolic syndrome.
AB  - OBJECTIVE: To compare the expression of the metabolic syndrome in Spain and San
      Antonio, TX, two populations with major differences regarding their
      cardiovascular risk profile. RESEARCH METHODS AND PROCEDURES: Cross-sectional
      analysis of population-based, epidemiological surveys using the metabolic
      syndrome definition of the National Cholesterol Education Program. In San
      Antonio, we limited our analysis to non-Hispanic whites because non-Hispanic
      whites are largely of European ancestry (n = 1339 in San Antonio and 2947 in
      Spain) RESULTS: In men, increased central adiposity was more prevalent in San
      Antonio than in Spain (29.7 vs. 23.0%, p < 0.0001); in women, it was less
      prevalent in San Antonio than in Spain (40.2 vs. 66.4%, p < 0.0001). The
      metabolic syndrome followed that same pattern: more prevalent in men (28.9 vs.
      20.8%, p = 0.019) and less in women from San Antonio (27.1 vs. 30.9%, p <
      0.0001). In subjects with the metabolic syndrome, most women had increased
      central adiposity (92.6% in San Antonio and 97.5% in Spain), and most men had
      either increased central adiposity or blood pressure (99.2% in San Antonio and
      95.0% in Spain). DISCUSSION: Contrary to men, the metabolic syndrome is more
      prevalent in Spanish women than in women from San Antonio with differences that
      mirror differences in central adiposity. Central adiposity and blood pressure may
      be used to exclude the metabolic syndrome. Considering recent secular trends in
      obesity, we predict there will be an increase in the prevalence of the metabolic
      syndrome in both populations in the coming years.

PMID- 14694213
TI  - Methods of estimation of visceral fat: advantages of ultrasonography.
AB  - OBJECTIVE: To compare methods for the assessment of visceral fat with computed
      tomography (CT) and establish cutoffs to define visceral obesity based on such
      alternative methods. RESEARCH METHODS AND PROCEDURES: One hundred women (50.4 +/-
      7.7 years; BMI 39.2 +/- 5.4 kg/m2 underwent anthropometric evaluation,
      bioelectrical impedance, DXA, abdominal ultrasonography (US), and CT scan.
      RESULTS: Waist circumference, waist-to-hip ratio (WHR), and US-determined
      visceral fat values showed the best correlation coefficients with visceral fat
      determined by CT (r = 0.55, 0.54, and 0.71, respectively; p < 0.01). Fat mass
      determined by DXA was inversely correlated with visceral-to-subcutaneous-fat
      ratio (r = -0.47, p < 0.01). Bioimpedance-determined fat mass and skinfolds were
      correlated with only subcutaneous abdominal fat quantified by CT. Linear
      regression indicated US visceral-fat distance and WHR as the main predictors of
      CT-determined visceral fat (adjusted r2 = 0.51, p < 0.01). A waist measurement of
      107 cm (82.7% specificity, 60.6% sensitivity) and WHR of 0.97 (78.8% specificity,
      63.8% sensitivity) were chosen as discriminator values corresponding with
      visceral obesity diagnosed by CT. A value of 6.90 cm for visceral fat US
      determined diagnosed visceral obesity with a specificity of 82.8%, a sensitivity
      of 69.2%, and a diagnostic concordance of 74% with CT. DISCUSSION: US seemed to
      be the best alternative method for the assessment of intra-abdominal fat in obese
      women. Its diagnostic value could be optimized by an anthropometric measurement.
      Prospective studies are needed to establish CT and US cutoffs for defining
      visceral-fat levels related to elevated cardiovascular risk.

PMID- 14694214
TI  - Insulin resistance in nondiabetic morbidly obese patients: effect of bariatric
      surgery.
AB  - OBJECTIVE: To evaluate insulin action on substrate use and insulinemia in
      nondiabetic class III obese patients before and after weight loss induced by
      bariatric surgery. RESEARCH METHODS AND PROCEDURES: Thirteen obese patients (four
      men/nine women; BMI = 56.3 +/- 2.7 kg/m2) and 13 lean subjects (five men/eight
      women; BMI = 22.4 +/- 0.5 kg/m2) underwent euglycemic clamp, oral glucose
      tolerance test, and indirect calorimetry. The study was carried out before (Study
      I) and after ( approximately 40% relative to initial body weight; Study II)
      weight loss induced by Roux-en-Y Gastric bypass with silastic ring surgery.
      RESULTS: The obese patients were insulin resistant (whole-body glucose use = 19.7
      +/- 1.5 vs. 51.5 +/- 2.4 micromol/min per kilogram fat-free mass, p < 0.0001) and
      hyperinsulinemic in the fasting state (332 +/- 86 vs. 85 +/- 5 pM, p < 0.0001)
      and during the oral glucose tolerance test compared with the lean subjects.
      Fasting plasma insulin normalized after weight loss, whereas whole-body glucose
      use increased (35.5 +/- 3.7 micromol/min per kilogram fat-free mass, p < 0.05 vs.
      Study I). The higher insulin clearance of obese did not change during the follow
      up period. Insulin-induced glucose oxidation and nonoxidative glucose disposal
      were lower in the obese compared with the lean group (all p < 0.05). In Study II,
      the former increased slightly, whereas nonoxidative glucose disposal reached
      values similar to those of the control group. Fasting lipid oxidation was higher
      in the obese than in the control group and did not change significantly in Study
      II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs.
      Study I). DISCUSSION: The rapid weight loss after surgery in obese class III
      patients normalized insulinemia and improved insulin sensitivity almost entirely
      due to glucose storage, whereas fasting lipid oxidation remained high.

PMID- 14694215
TI  - Obesity modulates the association among APOE genotype, insulin, and glucose in
      men.
AB  - OBJECTIVE: Obesity, insulin resistance, and apolipoprotein E (APOE) genotype have
      all been associated with coronary heart disease. We examined the interaction
      between obesity and APOE genotype in determining fasting insulin and glucose
      levels. RESEARCH METHODS AND PROCEDURES: From 1991 to 1995, 3799 subjects
      underwent a clinical examination and fasting insulin and glucose measurement.
      APOE genotypes were determined on 3500 participants. Participants taking oral
      hypoglycemic drugs or insulin preparations or with the rare APOE2/4 genotype were
      excluded. Finally, 2929 individuals were included in the present analysis.
      RESULTS: In men, we observed a statistically significant interaction between
      obesity and APOE genotype on insulin and glucose level (p = 0.003 and 0.008,
      respectively). Obese men with the APOE4 genotype presented with higher levels of
      insulin and glucose than obese men in the other genotype groups. No association
      between genotype and insulin or glucose in nonobese men was observed. Obesity was
      associated with higher insulin levels in the three APOE genotypes groups, whereas
      obesity was directly associated with glucose in those with the APOE4 genotype. In
      women, the effect of interaction between APOE genotype and obesity on fasting
      insulin and glucose was not statistically significant. Obesity was associated
      with higher levels of fasting insulin and glucose. APOE genotype was not
      associated with insulin or glucose. DISCUSSION: Obesity modulates the association
      between the APOE genotype and fasting insulin and glucose levels in men. Although
      weight control is important in all people, it may be especially important in
      APOE4 men to modify potentially elevated fasting insulin and glucose levels.

PMID- 14694216
TI  - Prior exercise increases dietary oleate, but not palmitate oxidation.
AB  - OBJECTIVE: Higher levels of physical activity have been associated with body
      weight maintenance, but previous work in our laboratory suggests that this is not
      purely related to energy balance. We hypothesize that this may be related to the
      partitioning of dietary fat between oxidation and storage. RESEARCH METHODS AND
      PROCEDURES: Healthy women (age 24 +/- 1 years, BMI = 21.2 +/- 0.4 kg/m2) were
      recruited to participate in rest (n = 10) or exercise sessions of light (n = 11),
      moderate (n = 10), and heavy (n = 7) exercise. All exercises (1250 kJ above rest)
      were performed on a stationary cycle inside of a whole-body calorimeter. [1
      (13)C]oleate and [d31]palmitate were given in a liquid meal 30 minutes post
      exercise. An additional study was done with identical exercise sessions, but with
      administration of an oral dose of [1-(13)C]acetate and [d3]acetate 30 minutes
      post-exercise to determine label sequestration. RESULTS: Cumulative oxidation of
      [1-(13)C]oleate was significantly greater after light (45 +/- 3%), moderate (54
      +/- 4%), and heavy (51 +/- 4%) exercise than that with rest (33 +/- 3%) (p =
      0.0008). Cumulative oxidation of [d31]palmitate did not differ among trials (12
      +/- 2%, 14 +/- 1%, 17 +/- 2%, and 14 +/- 2% for rest, light, moderate, and heavy,
      respectively; p = 0.30). DISCUSSION: Exercise standardized for energy expenditure
      increases monounsaturated fat oxidation more than saturated fat oxidation and
      that the increase occurs regardless of intensity. Recommendations for physical
      activity for the purposes of weight control may be specific for dietary fat
      composition.

PMID- 14694217
TI  - Bariatric surgeries in north Carolina, 1990 to 2001: a gender comparison.
AB  - OBJECTIVE: The purpose of this research was to determine the number of bariatric
      procedures in obese men and women in a well-defined population and to examine
      gender differences among bariatric patients. RESEARCH METHODS AND PROCEDURES:
      Data on bariatric patients were taken from the North Carolina Hospital Discharge
      Database, which contains information on all nonfederal hospital discharges in
      North Carolina from 1990 to 2001. Using North Carolina Hospital Discharge Data,
      Census North Carolina resident estimates, and North Carolina obesity prevalence
      estimates, we constructed annual rates for bariatric procedures for the obese
      male and female population in North Carolina. RESULTS: Overall, 2197 bariatric
      procedures were performed between 1990 and 2001. The annual rate of bariatric
      procedures in obese women increased rapidly, particularly between 1998 and 2001,
      whereas the increase for men was considerably less than that for women.
      Controlling for age and year of procedure, the odds ratio for obese female North
      Carolina residents of having a bariatric procedure was 4.96 (95% confidence
      interval: 4.39, 5.59) and of having a Roux-en-Y procedure was 5.57 (95%
      confidence interval: 4.67, 6.64) compared with obese male North Carolina
      residents. Controlling for age, comorbidity burden, payment source, and year of
      procedure, obese male North Carolina residents had a significantly greater (22%)
      amount of inpatient days than obese female North Carolina residents. DISCUSSION:
      After controlling for population rates of obesity and year of procedure, women
      are more likely than men to undergo bariatric surgery, suggesting that gender
      related factors may influence use. More research is needed to determine the
      causes for this large gender disparity.

PMID- 14694218
TI  - A prospective study of the effect of childbearing on weight gain in African
      American women.
AB  - OBJECTIVE: To prospectively assess the influence of bearing a first, second, or
      later child on weight gain among African-American women in the context of other
      risk factors. RESEARCH METHODS AND PROCEDURES: Data were obtained in a
      prospective follow-up study of African-American women from across the U.S. who
      are participants in the Black Women's Health Study. Postal questionnaires were
      used to collect baseline data in 1995 and follow-up data in 1997 and 1999. Parous
      and nulliparous women (11,196) (21 to 39 years old at baseline), of whom 1230 had
      a singleton birth during follow-up, are the subjects of the present analyses. We
      assessed change in BMI (kilograms per meter squared) in relation to childbearing
      during 4 years of follow-up, with use of multivariable linear regression to
      control for important risk factors. RESULTS: During 4 years of follow-up, the BMI
      of participants increased by an average of 1.6 kg/m2, equivalent to a weight gain
      of approximately 4.4 kg. Women who had a child during follow-up gained more
      weight than women who remained nulliparous, and those who had a first child
      gained more than those who had a second or later child. The weight gain
      associated with childbearing increased with increasing baseline BMI and was
      appreciable among heavier women. For example, among women with a baseline index
      of 36, the increase in BMI for women who bore a first child was 1.1 kg/m2 more
      than that of nulliparous women, equivalent to a difference in weight gain of
      approximately 3.0 kg. DISCUSSION: Childbearing is an important contributor to
      weight gain among African-American women.

PMID- 14694219
TI  - Self-selected macronutrient diet affects energy and glucose metabolism in brown
      fat-ablated mice.
AB  - OBJECTIVE: Obese transgenic UCP-DTA mice have largely ablated brown adipose
      tissue and develop obesity and diabetes, which are highly susceptible to a high
      fat diet. We investigated macronutrient self-selection and its effect on
      development of obesity, diabetes, and energy homeostasis in UCP-DTA mice.
      RESEARCH METHODS AND PROCEDURES: UCP-DTA and wild-type littermates were fed a
      semisynthetic macronutrient choice diet (CD) ad libitum from weaning until 17
      weeks. Energy homeostasis was assessed by measurement of food intake, food
      digestibility, body composition, and energy expenditure. Diabetes was assessed by
      blood glucose measurements and insulin tolerance test. RESULTS: Wild-type and UCP
      DTA mice showed a high fat preference and increased energy digestion on CD
      compared with a low-fat standard diet. On CD, wild-type mice accumulated less
      body fat (16.9%) than UCP-DTA (32.6%) mice, although they had a higher overall
      energy intake. Compared with wild-type mice, resting metabolic rate was reduced
      in UCP-DTA mice irrespective of diet. UCP-DTA mice progressively decreased their
      carbohydrate intake, resulting in an almost complete avoidance of carbohydrate.
      UCP-DTA mice developed severe insulin resistance but showed decreased fed and
      fasted blood glucose on CD. DISCUSSION: In contrast to wild-type mice, UCP-DTA
      mice were not able to reduce their weight gain efficiency on CD. This suggests
      that, because of the high fat preference of the background strain and the
      increased metabolic efficiency, brown adipose tissue-deficient mice still develop
      obesity and insulin resistance on a macronutrient CD even when decreasing overall
      energy intake. Through the avoidance of carbohydrates, however, they are able to
      maintain normoglycemia.

PMID- 14694220
TI  - Comparison of Hologic QDR-1000/W and 4500W DXA Scanners in 13- to 18-Year Olds.
AB  - OBJECTIVE: Body composition measurements made using Hologic QDR-1000/W pencil
      beam and QDR-4500W fan-beam scanners (Bedford, MA) were compared in a sample of
      13- to 18-year-old white and black youth (n = 219). RESEARCH METHODS AND
      PROCEDURES: Total fat (FAT), fat-free soft tissue (FFST), bone mineral content
      (BMC), bone mineral density (BMD), and percent body fat (%BF) were compared
      between repeated measurements using the QDR-4500 and between the two scanners
      using mixed model ANOVA. Intraclass correlation coefficients and Bland-Altman
      limits of agreement were used to evaluate inter- and intrascanner reliability.
      RESULTS: Intraclass correlation coefficients for repeated measurements using the
      QDR-4500 ranged from 0.997 to 0.999 for FAT, %BF, FFST, and BMC and 0.987 for
      BMD. Mean measurements made using the two scanners differed significantly for
      FAT, %BF, BMC, and BMD (p < 0.0001), and scan by sex interactions were
      significant (all p < 0.0005). There were no significant differences in mean
      measurements between repeat scans using the QDR-4500 (all p > 0.19). Limits of
      agreement for measurements of FAT, FFST, and %BF made using the two scanners were
      approximately three times as wide as those for two measurements using the QDR
      4500. For lower values of FAT and %BF, the QDR-4500 gave higher measurements than
      the QDR-1000, whereas at higher values, this relationship was reversed. The QDR
      1000 tended to give higher BMC measurements, with larger differences for higher
      values. DISCUSSION: Using different models of DXA scanners within a study may
      reduce precision of body composition measurement. This issue needs to be
      considered in the design of longitudinal studies.

PMID- 14694221
TI  - Estimating body fat from anthropometry and isotopic dilution: a four-country
      comparison.
AB  - OBJECTIVE: The goal was to assess the ability of BMI to predict body fat (BF)
      among youths in four countries and identify the degree to which additional
      anthropometric measures improve this prediction. BMI is widely recommended as an
      indicator of overweight. However, whether BMI adequately estimates BF and has the
      same meaning in different ethnic groups and youths has been questioned. RESEARCH
      METHODS AND PROCEDURES: Data come from 456 Filipino, Chinese, Russian, and black
      South African youths, 6 to 16 years old. Percentage BF and fat mass index (FMI)
      were estimated by the deuterium dilution method. Skinfold thicknesses (triceps,
      subscapular, and suprailiac) and weight and height measures were collected.
      Percentage BF was regressed first on BMI and age and then with the addition of
      the skinfold measures. Linear models were run separately by country and sex. The
      models were repeated with FMI as the outcome. RESULTS: The R2 values from the
      percentage BF models ranged from 0.13 to 0.69 in the first models to 0.38 to 0.81
      in the full models. The values were lowest among Russian males > or = 13 years
      and Russian females > or = 13 years of age in the reduced and full models,
      respectively, and were highest among Chinese females. Using FMI as the outcome
      did not meaningfully change the results. DISCUSSION: The ability of BMI to
      adequately predict BF and the additional predictivity of anthropometric measures
      varied widely across the samples, making its uniform use as a proxy for BF in
      youths from different countries questionable.

PMID- 14694222
TI  - Cross-sectional relationship of pedometer-determined ambulatory activity to
      indicators of health.
AB  - OBJECTIVE: To describe the cross-sectional relationship between an objective
      measure of walking (pedometer-determined steps/day) and general indicators of
      health, a prior diagnosis of one or more components of the metabolic syndrome,
      and self-reported occupational activity in a generally sedentary working
      population. RESEARCH METHODS AND PROCEDURES: Steps/day were compared with
      previous diagnosis of one or more components of the metabolic syndrome (by self
      administered questionnaire) and with general health indicators including BMI,
      waist circumference, resting heart rate, and blood pressure in 182 subjects in
      Prince Edward Island, Canada. Study participants were volunteer employees
      recruited from five workplaces where, in general, the job types were moderately
      or highly sedentary. RESULTS: Steps/day were 7230 +/- SD 3447 for women (n = 153)
      and 8265 +/- 2849 (n = 21) for men. Pedometer-determined steps/day were
      associated inversely with BMI (r = -0.4005, p < 0.0001) in all participants and
      waist circumference in females only (r = -0.4303, p < 0.0001). There was a low
      correlation between steps/day and diastolic blood pressure in the whole sample (r
      = -0.2140, p = 0.0383). Participants who reported a prior diagnosis of one or
      more components of the metabolic syndrome (hypertension, hypercholesterolemia,
      heart disease, or type 2 diabetes) took fewer steps/day than healthy participants
      (p = 0.0254). Pedometer-determined steps/day were positively associated with self
      reported occupational activity (p = 0.0002). DISCUSSION: Fewer steps/day are
      associated with increased BMI, waist circumference, diastolic blood pressure, and
      components of the metabolic syndrome. Low occupational activity is a contributing
      factor to low total ambulatory activity.

PMID- 14694223
TI  - Stimulatory effect of leptin on nitric oxide production is impaired in dietary
      induced obesity.
AB  - OBJECTIVE: We investigated the effect of leptin on nitric oxide production in
      lean and rats made obese by a high-calorie diet. RESEARCH METHODS AND PROCEDURES:
      The animals were placed in metabolic cages, and urine was collected in 2-hour
      periods after leptin (1 mg/kg intraperintoneally) or vehicle administration.
      Blood was obtained 0.5, 1, 2, 4, or 6 hours after injection. RESULTS: Leptin had
      no effect on systolic blood pressure in either lean or obese animals. Plasma
      concentration of NO metabolites (nitrites + nitrates, NOx) increased in lean rats
      by 31.5%, 58.0%, and 27.9% at 1, 2, and 4 hours after leptin injection,
      respectively. In the obese group, plasma NOx increased only at 2 hours (+36.5%).
      Leptin increased urinary NOx excretion by 31.8% in the first 2-hour period after
      injection in lean but not in obese rats. In lean animals, leptin elevated plasma
      cyclic 3',5'-guanosine monophosphate (cGMP) at 1, 2, and 4 hours by 35.3%, 96.3%,
      and 57.3%, respectively. In the obese group, plasma cGMP was higher only at 2 and
      4 hours (+44.6% and +32.1%, respectively). Urinary excretion of cGMP increased in
      lean animals by 67.1% in the first period and by 50.4% in the second period. In
      the obese group, leptin induced a 53.9% increase in urinary cGMP excretion only
      in the first 2-hour period. DISCUSSION: The stimulatory effect of leptin on NO
      production is impaired in dietary-induced obesity; however, leptin does not
      increase blood pressure in obese animals, suggesting that other NO-independent
      depressor mechanisms are stimulated.

PMID- 14694224
TI  - Objectively measured intensity of physical activity and adiposity in middle-aged
      women.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship between
      objectively measured physical activity (ACT), particularly intensity of physical
      activity (iACT), and body fat percentage (BF%) in 278 middle-aged women.
      Secondary purposes were to ascertain the association between physical activity
      duration (dACT) and BF% and the extent to which potentially confounding factors,
      including total ACT, energy intake, body weight, and season of assessment,
      influenced the relationship between iACT and BF%. RESEARCH METHODS AND
      PROCEDURES: A cross-sectional design was used. Subjects were apparently healthy,
      35 to 45 years old, premenopausal, nonsmokers, with BMIs < 30 kg/m2.
      Approximately 90 percent were white, 81% were married, and 37% were college
      graduates. ACT was assessed using Computer Science and Application accelerometers
      worn for 7 consecutive days. The accelerometers recorded movement continuously,
      and activity counts were collapsed into 10-minute epochs. Intensity was indexed
      using seven activity count cut-off points, and duration was based on the number
      of 10-minute epochs at each intensity level. BF% was assessed using multiple
      measurements in the Bod Pod. Energy intake was measured using 7-day weighed diet
      records during the same week subjects wore the accelerometers. RESULTS: BF% was
      strongly and inversely associated with iACT and dACT. Controlling for energy
      intake and body weight strengthened the relationships among iACT, dACT, and BF%.
      Control of total ACT weakened the association. DISCUSSION: Engaging in higher
      intensity and/or longer duration ACT is associated with lower BF% compared with
      lower intensity and/or shorter durations of activity.

PMID- 14694225
TI  - Lifestyle intervention according to general recommendations improves glucose
      tolerance.
AB  - OBJECTIVE: Changing dietary and physical activity habits has the potential to
      postpone or prevent the development of type 2 diabetes. However, it needs to be
      assessed whether moderate interventions, in agreement with current guidelines for
      the general population, are effective. We evaluated the impact of a 2-year
      combined diet and physical activity intervention program on glucose tolerance in
      Dutch subjects at increased risk for developing diabetes. RESEARCH METHODS AND
      PROCEDURES: Subjects with glucose intolerance were randomly assigned to either
      the lifestyle intervention group (INT) or control group (CON). The INT received
      regular dietary advice and was stimulated to increase their physical activity.
      The CON received a brief leaflet about healthy diet and increased physical
      activity. Primary outcome measure was the change in glucose tolerance. RESULTS:
      In total, 88 subjects completed 2 years of intervention (40 subjects in the INT,
      48 subjects in the CON, mean BMI 29.4 kg/m2). Subjects in the INT reduced their
      body weight, waist circumference, and (saturated) fat intake and improved their
      aerobic capacity. Two-hour plasma glucose concentration declined from 8.7 to 8.0
      mM in the INT and rose from 8.6 to 9.4 mM in the CON (p < 0.01). Subjects
      adherent to both the diet and exercise intervention showed the largest reduction
      in 2-hour glucose levels. DISCUSSION: Our results showed that a lifestyle
      intervention program according to general recommendations improves glucose
      tolerance, even in a less obese and more physical active population. Furthermore,
      our results underscore the importance of combining diet and physical activity to
      improve glucose tolerance and insulin resistance.

PMID- 14694226
TI  - Relationship of adiposity to subclinical atherosclerosis in obese patients with
      type 2 diabetes.
AB  - OBJECTIVE: There is an increased prevalence of macrovascular disease in type 2
      diabetes. The pathogenesis has been related to metabolic risk factors, insulin
      resistance, and obesity. One of the strongest predictors is the presence of
      subclinical atherosclerosis. This study was designed to examine the relationship
      between obesity and regional patterns of adiposity, insulin resistance, and five
      independent measures of subclinical atherosclerosis. RESEARCH METHODS AND
      PROCEDURES: Fifty-two overweight and obese men and women with type 2 diabetes of
      relatively short known duration were examined. Measures of subclinical vascular
      disease were assessment of arterial stiffness by pulse wave velocity, ultrasound
      measurement of the carotid artery intimal-medial thickness and plaque index, and
      measurement of the extent of coronary and aortic calcification using electron
      beam computed tomography. Insulin resistance was measured using the
      hyperinsulinemic euglycemic clamp. Body composition was measured using DXA and
      computed tomography. RESULTS: Adiposity was a strong determinant of pulse wave
      velocity. Carotid intimal-medial thickness was correlated with age, low-density
      lipoprotein-cholesterol, and hyperglycemia, but not with adiposity. Hyperglycemia
      and plasma activator inhibitor-1 were significant correlates of the carotid
      artery plaque index. Coronary calcium scores were significantly correlated with
      age and interleukin-6 and significantly and negatively correlated to insulin
      sensitivity index. DISCUSSION: These findings suggest that obesity may play an
      important role in the early phase of subclinical macrovascular disease related to
      vessel stiffness, whereas hyperglycemia and insulin resistance in conjunction
      with other risk factors have important roles in progression from vessel stiffness
      to atheroma formation in type 2 diabetes.

PMID- 14694227
TI  - Letter: Glucocorticoid receptor N363S variant in obesity: comes into vanity and
      goes into darkness.

PMID- 14694232
TI  - Delays in managing lung cancer.

PMID- 14694233
TI  - The developing story of antioxidants and asthma.

PMID- 14694234
TI  - Sleep disordered breathing awoken.

PMID- 14694237
TI  - Genetic polymorphism of GSTM1 and antioxidant supplementation influence lung
      function in relation to ozone exposure in asthmatic children in Mexico City.
AB  - BACKGROUND: We recently reported that antioxidant supplementation with vitamins C
      and E mitigated ozone related decline in forced expiratory flow (FEF(25-75)) in
      158 asthmatic children in an area with high ozone exposure in Mexico City.
      METHODS: A study was undertaken to determine whether deletion of glutathione S
      transferase M1 (GSTM1 null genotype), a gene involved in response to oxidative
      stress, influences ozone related decline in FEF(25-75) and the benefit of
      antioxidant supplementation. RESULTS: GSTM1 null children receiving placebo had
      significant ozone related decrements in FEF(25-75) (percentage change per 50 ppb
      of ozone 2.9 (95% CI -5.2 to -0.6), p=0.01); GSTM1 positive children did not.
      Conversely, the effect of antioxidants was stronger in children with the GSTM1
      null genotype. CONCLUSIONS: Asthmatic children with a genetic deficiency of GSTM1
      may be more susceptible to the deleterious effects of ozone on the small airways
      and might derive greater benefit from antioxidant supplementation.

PMID- 14694239
TI  - Early prescriptions of antibiotics and the risk of allergic disease in adults: a
      cohort study.
AB  - BACKGROUND: It is frequently asserted that antibiotic prescriptions in childhood
      are associated with the development of allergic disease, especially asthma. A
      study was undertaken to establish the direction of this relationship. METHODS: A
      retrospective cohort study of 746 adults was performed in three general
      practices. Antibiotic prescriptions in the first 5 years of life, collected from
      contemporary medical records, were related to self-reports of asthma and hay
      fever and the results of skin prick testing with common aeroallergens. RESULTS:
      There was no relationship between early antibiotic prescription and atopy, either
      for all antibiotic use (OR 1.01) or for antibiotics prescribed at different ages.
      The significant associations between prescriptions at ages 4 and 5 and hay fever
      (OR 1.23 and 1.16, respectively) were explained by coexisting asthma.
      Relationships between antibiotic use and asthma (allergic or otherwise) were
      statistically significant and strengthened with increasing age of prescription,
      but were largely confined to antibiotics prescribed for lower respiratory
      symptoms. CONCLUSIONS: The reported associations between childhood antibiotic use
      and asthma are most plausibly explained by "reverse causation"--the tendency for
      prescriptions to be written for the early manifestations of pre-existing asthma.

PMID- 14694240
TI  - Clinical dose-response relationship of fluticasone propionate in adults with
      asthma.
AB  - BACKGROUND: A study was undertaken to examine the dose-response relation of
      inhaled fluticasone in adolescents and adults with asthma. METHODS: A meta
      analysis was carried out of randomised clinical trials that presented data on at
      least one outcome measure of asthma and that used at least two doses of
      fluticasone given twice daily. The main outcome measures were forced expiratory
      volume in 1 second (FEV1), morning peak expiratory flow (amPEF), beta agonist
      use, and withdrawals due to exacerbations of asthma. RESULTS: Seven studies of
      2431 adolescents and adults with moderate to severe asthma met the inclusion
      criteria for the meta-analysis. Four studies examined a dose of >500 microg/day.
      For all outcome measures there were no statistically significant differences
      between a dose of 200 v 500 microg/day, 500 v 1000 microg/day, and 200 v > or
      =500 microg/day, although the point estimates favoured the higher doses. The mean
      improvement for FEV1 and amPEF resulting from an increase in dose from 200 to >
      or =500 microg/day was 0.07 l (95% CI -0.01 to 0.14) and 5.9 l/min (95% CI -3.0
      to 15.3), respectively. The odds ratio for withdrawals with 200 microg/day
      compared with > or =500 microg/day was 1.27 (95% CI 0.78 to 2.07). CONCLUSIONS:
      In adolescents and adults with asthma, most of the therapeutic benefit of
      fluticasone is achieved with a total daily dose of 200 microg/day with minimal
      further clinical benefit achieved with higher doses. This conclusion is qualified
      by the recognition that there is considerable individual variability in the
      response to inhaled corticosteroids in asthma, which would suggest that some
      patients may obtain a greater clinical benefit at higher doses.

PMID- 14694241
TI  - Use of sequential quadrupling dose regimens to study efficacy of inhaled
      corticosteroids in asthma.
AB  - BACKGROUND: Inhaled corticosteroids are widely used to treat asthma. There is a
      need to be able to compare different inhaled corticosteroids and different doses
      of an inhaled corticosteroid to determine potency and dose equivalence, but
      measuring efficacy in a dose related manner is difficult because of their slow
      onset of action. There is uncertainty about the role of sequential dosing
      regimens and the best end point for such studies. We have explored the use of
      sequential quadrupling dose regimens and a range of end points to assess the
      response to budesonide in subjects with asthma. METHODS: 21 subjects with mild
      asthma, aged 18-65, took part in a randomised three way crossover study comparing
      two sequential and one non-sequential regimen, separated by at least 3 weeks. The
      sequential regimens consisted of increasing doses of inhaled budesonide (100, 400
      1600 microg/day) with each dose being given for 1 or 2 weeks; the non-sequential
      regimen consisted of 1600 microg/day for 2 weeks with end points measured after 1
      and 2 weeks. The end points studied included the provocative dose of adenosine
      monophosphate causing a 20% fall in forced expiratory volume in 1 second
      (PD20AMP), lung function, symptoms, and bronchodilator use. RESULTS: There was a
      dose related increase in PD20AMP with both sequential dose regimens. The increase
      in PD20AMP ranged from 1.49 doubling doses (DD) following the lowest dose (100
      microg/day) to 3.1 DD following the highest dose (1600 microg/day) in the 1 week
      sequential regimen and from 1.98 to 4.03 DD in the 2 week sequential regimen;
      standard deviations (SD) for the changes in PD20AMP ranged from 1.3 to 2.6 DD.
      Changes in forced expiratory volume in 1 second (FEV1) and morning peak
      expiratory flow rate (PEFR) were dose related but small and more variable
      (maximum change in FEV1=148 ml, SD 228 ml), while changes in evening PEFR,
      symptoms, and bronchodilator use were small and not dose related. Change in
      PD20AMP after budesonide 1600 microg did not differ significantly between
      regimens. CONCLUSION: Combining PD20AMP measurements with a sequential regimen of
      three quadrupling doses of an inhaled corticosteroid given for 1 or 2 weeks
      provides clear dose-response curves for comparative studies. PD20AMP is a more
      sensitive end point for this purpose than FEV1, PEFR, symptoms, or relief inhaler
      use.

PMID- 14694242
TI  - Time course of action of two inhaled corticosteroids, fluticasone propionate and
      budesonide.
AB  - BACKGROUND: It is important to be able to compare the efficacy and systemic
      effects of inhaled corticosteroids but their slow onset of action makes it
      difficult to measure the maximum response to a given dose. Submaximal responses
      could be compared if the time course of action of the inhaled corticosteroids
      being compared was similar. We have compared the time course of action of
      fluticasone and budesonide, measuring response as change in the provocative dose
      of adenosine monophosphate causing a 20% fall in forced expiratory volume in 1
      second (PD20AMP). METHODS: Eighteen subjects with mild asthma, aged 18-65, took
      part in a three way randomised crossover study. Subjects took fluticasone (1500
      microg/day), budesonide (1600 microg/day), and placebo each for 4 weeks with a
      washout period of at least 2 weeks between treatments; PD20AMP and forced
      expiratory volume in 1 second (FEV1) were measured during and after treatment.
      The time taken to achieve 50% of the maximum response (T50%) was compared as a
      measure of onset of action. RESULTS: There was a progressive increase in PD20AMP
      during the 4 weeks of treatment with both fluticasone and budesonide but not
      placebo; the increase after 1 and 4 weeks was 2.28 and 4.50 doubling doses (DD)
      for fluticasone and 2.49 and 3.65 DD for budesonide. T50% was 9.3 days for
      fluticasone and 7.5 days for budesonide with a median difference between
      fluticasone and budesonide of 0.1 days (95% CI -1.4 to 2.65). There was a wide
      range of response to both inhaled corticosteroids but good correlation between
      the response to fluticasone and budesonide within subjects. FEV1 and morning peak
      expiratory flow rate (PEFR) increased during the first week of both active
      treatments and were stable thereafter. There was a small progressive improvement
      in nocturnal symptoms with both active treatments. CONCLUSION: PD20AMP was a more
      sensitive marker of response to inhaled corticosteroid therapy than FEV1 and
      PEFR. The time course of action of fluticasone and budesonide on PD20AMP is
      similar, suggesting that comparative studies of their efficacy using 1 or 2 week
      treatment periods are valid. When a new inhaled corticosteroid becomes available,
      a pilot study comparing its time course of action with that of an established
      corticosteroid should allow comparative studies to be performed more efficiently.

PMID- 14694243
TI  - Reduction of bleomycin induced lung fibrosis by candesartan cilexetil, an
      angiotensin II type 1 receptor antagonist.
AB  - BACKGROUND: Signalling of angiotensin II via angiotensin II type 1 receptor (AT1)
      promotes cardiac and renal fibrosis, but its role in lung fibrosis is little
      understood. Using a rat bleomycin (BLM) induced model of pulmonary fibrosis, we
      examined the expression of AT1 in the lung and the effect of an AT1 antagonist on
      pulmonary fibrosis. METHODS: Adult male Sprague-Dawley rats were given 0.3 mg/kg
      BLM intratracheally. Two days earlier they had received 10 mg/kg/day of the AT1
      antagonist candesartan cilexetil mixed in the drinking water. AT1 expression in
      the lungs was examined by immunohistochemistry and immunoblot methods. The effect
      of the AT1 antagonist on pulmonary fibrosis was studied by analysis of
      bronchoalveolar lavage (BAL) fluid, histopathology, and hydroxyproline assay.
      RESULTS: Immunohistochemical studies showed overexpression of AT1 in inflammatory
      immune cells, alveolar type II cells, and fibroblasts. A quantitative assay for
      AT1 showed that AT1 expression was significantly upregulated in cells from BAL
      fluid after day 3 and in the lung homogenates after day 21. Candesartan cilexetil
      significantly inhibited the increase in total protein and albumin, as well as the
      increase in total cells and neutrophils in BAL fluid. On day 21 candesartan
      cilexetil also ameliorated morphological changes and an increased amount of
      hydroxyproline in lung homogenates. In addition, BLM increased the expression of
      transforming growth factor (TGF)-beta1 in BAL fluid on day 7; this increase was
      significantly reduced by candesartan cilexetil. CONCLUSION: AT1 expression is
      upregulated in fibrotic lungs. Angiotensin II promotes lung fibrosis via AT1 and,
      presumably, in part via TGF-beta1.

PMID- 14694246
TI  - Effects of antiplatelet agents on pulmonary haemodynamic response to fMLP in
      endotoxin primed rats.
AB  - BACKGROUND: The interaction between neutrophils and platelets may be important in
      the modulation of pulmonary haemodynamics under systemic inflammatory conditions.
      A study was undertaken to examine whether antiplatelet agents inhibit platelet
      neutrophil adherence and ameliorate the pulmonary haemodynamic response to fMLP
      by inhibiting thromboxane release in endotoxin primed lungs. fMLP stimulates
      neutrophils but not platelets; however, thromboxane synthesis in neutrophils is
      very low. METHODS: Rats were pretreated with either cilostazol (300 mg/kg) or
      aspirin (50 mg/kg) before endotoxin priming (5 mg/kg). Platelets in the lung were
      identified by fluorescent immunohistochemistry. Platelet-neutrophil adherence was
      analysed by flow cytometry of the lung vascular flush. The effect of fMLP (10(-6)
      M) on thromboxane release, lung weight (an indicator of pulmonary
      vasoconstriction), and lung filtration coefficient was determined in an isolated
      lung system perfused at a constant pressure difference. RESULTS: Endotoxin
      induced platelet accumulation and platelet-neutrophil adherence in the lung
      capillary were completely inhibited by cilostazol and aspirin while neutrophil
      recruitment was not affected. The fMLP challenge caused a significant increase in
      thromboxane B2 levels in endotoxin primed lungs. The fMLP induced decrease in
      lung weight was enhanced by endotoxin priming (from -4.9 to -63.9 mg, 95% CI of
      mean difference -99.5 to -10.5 mg, p<0.05). The fMLP induced increase in the lung
      filtration coefficient was also enhanced by endotoxin priming (from 0.63 to 2.40
      mg/min/cm H2O/g, 95% CI of mean difference 1.17 to 2.37 mg/min/cm H2O/g, p<0.05).
      Treatment with cilostazol and aspirin completely inhibited the enhanced pulmonary
      haemodynamic response to fMLP. CONCLUSION: The neutrophil-platelet interaction is
      of critical importance in the modulation of pulmonary haemodynamics via
      thromboxane.

PMID- 14694247
TI  - Effect of delays on prognosis in patients with non-small cell lung cancer.
AB  - BACKGROUND: The effect of delay on survival in lung cancer remains uncertain. It
      is suggested that prompt management of non-small cell lung cancer (NSCLC) can
      influence prognosis. This study was undertaken to examine the relation between
      delay and prognosis in patients with NSCLC and to investigate the delay time from
      first symptom and from first hospital visit to start of treatment. METHODS: Two
      types of delay (symptom to treatment delay and hospital delay) were investigated
      in 466 patients treated for NSCLC at two institutions in central Sweden. Delays
      in relation to clinical characteristics were compared and the effects of delay
      times and other relevant factors on survival were assessed in multivariate
      analyses. RESULTS: Thirty five per cent of patients received treatment within 4
      weeks of the first hospital visit and 52% within 6 weeks. Median symptom to
      treatment delay was 4.6 months and median hospital delay 1.6 months. Older age,
      advanced tumour stage, and non-surgical treatment were independently related to
      poor survival. Both prolonged hospital delay and symptom to treatment delay
      provided additional information when considered separately. In a final
      multivariate model only increased symptom to treatment delay gave significant
      information of a better prognosis. There was an association between a short delay
      and a poor prognosis which was most pronounced in patients with advanced disease.
      CONCLUSION: When considering the whole study population and all stages of tumour
      together, shorter delay was associated with a poorer prognosis. This is likely to
      reflect the fact that patients with severe signs and symptoms receive prompt
      treatment. These findings indicate that the waiting time for treatment in
      patients with NSCLC is longer than recommended.

PMID- 14694248
TI  - Intranasal corticosteroid therapy for obstructive sleep apnoea in patients with
      co-existing rhinitis.
AB  - BACKGROUND: Increased nasal airflow resistance (NAR) may contribute to the
      pathophysiology of obstructive sleep apnoea syndrome (OSAS) but studies
      investigating the effects of relieving nasal obstruction in OSAS have produced
      differing results. There are no reports of intranasal corticosteroid therapy in
      adult OSAS patients with reversible nasal obstruction. METHODS: We evaluated an
      intranasal corticosteroid, fluticasone propionate, in 24 consecutive snorers with
      associated rhinitis using a randomised, placebo controlled, crossover design.
      Patients underwent polysomnography, snoring noise, and NAR measurements at
      baseline and after each 4 week treatment period. RESULTS: Twenty three patients
      completed the protocol and were divided into an apnoeic group (group A; 13
      patients) and a non-apnoeic snoring group (group S; 10 patients) based on an
      apnoea-hypopnoea frequency (AHI) of > or =10/h or <10/h. AHI was significantly
      lower following treatment with fluticasone than with placebo in the total
      population (median (quartile range) 11.9 (22.6) v 20 (26.3); p<0.05) and in group
      A (23.3 (21.3) v 30.3 (31.9); p<0.05). Median (95% confidence interval) within
      subject differences for AHI were -3.2 (-17.7 to -0.2) in the total population and
      -6.5 (-29.5 to 1.8) in group A. NAR was also lower on fluticasone (2.74 (1.21) v
      3.27 (1.38), p<0.01), within subject difference being -0.45 (95% CI -0.87 to 
      0.21). The changes in AHI and NAR in group A were significantly correlated
      (r=0.56; p<0.05). Snoring noise and sleep quality were unchanged but daily diary
      records indicated subjective improvements in nasal congestion and daytime
      alertness with fluticasone (p<0.02). CONCLUSIONS: Intranasal fluticasone is of
      benefit to some patients with OSAS and rhinitis. The data suggest that this form
      of nasal obstruction may contribute to the pathophysiology of OSAS.

PMID- 14694250
TI  - Time course of changes in driving simulator performance with and without
      treatment in patients with sleep apnoea hypopnoea syndrome.
AB  - BACKGROUND: Improvements in driving simulator performance have been demonstrated
      in patients with sleep apnoea hypopnoea syndrome (SAHS) after several months of
      treatment, but it is not known how quickly these improvements are achieved and
      lost. The aim of this study was to assess the time course of changes in driving
      simulator performance in patients with SAHS following treatment with continuous
      positive airways pressure (CPAP). METHODS: Eighteen patients with severe SAHS
      performed a driving simulator test at baseline (before treatment) and at days 1,
      3, and 7 of a 2 week CPAP trial period. CPAP was then discontinued and the
      patients performed three further driving simulator tests after 1, 3, and 7 days.
      Eighteen patients with severe SAHS acted as controls and performed the driving
      simulator test on seven occasions in a pattern similar to that of the treated
      patients. RESULTS: Significant improvements in tracking error (p=0.004), reaction
      time (p=0.036), and the number of off road events per hour (p=0.032) were seen in
      the CPAP treated group compared with the controls at 7 days. Following
      discontinuation of CPAP for 7 days a significant difference in driving simulator
      performance persisted between the two groups, but the size of the difference had
      reduced. CONCLUSION: Driving simulator performance in patients with severe SAHS
      improves within the first few days of starting CPAP and these improvements appear
      to be sustained for up to 1 week after withdrawal. Further data about the
      usefulness of driving simulators in predicting safe driving are needed before
      these results can be used in advising patients on driving. However, the data
      appear to suggest that driving can be safely resumed after a few days of
      effective CPAP treatment.

PMID- 14694251
TI  - Low birth weight for gestation and airway function in infancy: exploring the
      fetal origins hypothesis.
AB  - BACKGROUND: Poor fetal growth has been associated with impaired airway function
      in adult life, but evidence linking birth weight and airway function in early
      childhood is sparse. We examined the hypothesis that low birth weight for
      gestation is associated with impaired airway function shortly after birth and
      that this is independent of impaired postnatal somatic growth. METHODS: Airway
      function was measured using the raised volume technique in healthy white infants
      of low (< or =10th centile) or appropriate (> or =20th centile) birth weight for
      gestation and was expressed as forced expiratory volume in 0.4 s (FEV0.4), forced
      vital capacity (FVC), and the maximal expired flow at 25% of forced vital
      capacity (MEF25). Infant length and weight, maternal height and weight, maternal
      report of smoking prenatally and postnatally, and parental occupation were
      recorded. RESULTS: Mothers of low birth weight for gestation infants (n=98) were
      lighter, shorter, and more likely to smoke and have partners in manual
      occupations. At 6 weeks their infants remained lighter and shorter than those of
      appropriate birth weight (n=136). FEV0.4, FVC, and MEF25 were reduced in infants
      of low birth weight for gestation, in those whose mothers smoked in pregnancy, or
      who were in manual occupations. After adjusting for relevant maternal and infant
      characteristics, infants in the low birth weight for gestation group experienced
      a mean reduction of 11 ml in FEV0.4 (95% CI 4 to 18; p=0.002), of 12 ml in FVC
      (95% CI 4 to 19; p=0.004), and of 28 ml/s in MEF25 (95% CI 7 to 48; p=0.03).
      CONCLUSIONS: Airway function is diminished in early postnatal life as a
      consequence of a complex causal pathway which includes social disadvantage as
      indicated by maternal social class, smoking and height, birth weight as a
      proximal and related consequence of these factors, and genetic predisposition to
      asthma. Further work is needed to establish the relevance of these findings to
      subsequent airway growth and development in later infancy and early childhood.

PMID- 14694252
TI  - Pulmonary function abnormalities in children with sickle cell disease.
AB  - BACKGROUND: Adults with sickle cell disease (SCD) have restrictive lung function
      abnormalities which are thought to result from repeated lung damage caused by
      episodes of pulmonary vaso-occlusion; such episodes start in childhood. A study
      was therefore undertaken to determine whether children with SCD have restrictive
      lung function abnormalities and whether the severity of such abnormalities
      increases with age. METHODS: Sixty four children with SCD aged 5-16 years and 64
      ethnic matched controls were recruited. Weight and sitting and standing height
      were measured, and lung function was assessed by measurement of lung volumes and
      forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and
      peak expiratory flow (PEF) before and after bronchodilator. RESULTS: Compared
      with the control subjects, the children with SCD had lower mean (SD) sitting
      height (69 (6.3) cm v 73 (7.7) cm; p=0.004), sitting:standing height ratio (0.50
      (0.02) v 0.51 (0.01); p<0.0001), weight (33 (10.9) kg v 41 (14.9) kg; p=0.001),
      functional residual capacity measured by a helium gas dilution technique (1.2
      (0.3) l v 1.3 (0.4) l; p=0.04), FEV1 (1.5 (0.5) l v 1.9 (0.7) l; p=0.0008), FVC
      (1.7 (0.6) l v 2.1 (0.8) l; p=0.001), and PEF (3.9 (1.3) l/s v 4.8 (1.5) l/s;
      p=0.0004). The effect of age on lung function differed significantly between the
      children with SCD and the controls for total lung capacity and vital capacity
      measured by plethysmography and functional residual capacity measured by helium
      gas dilution. CONCLUSION: Lung function differs significantly in children with
      SCD compared with ethnic matched controls of a similar age. Our results suggest
      that restrictive abnormalities may become more prominent with increasing age.

PMID- 14694253
TI  - Cough. 4: Cough in asthma and eosinophilic bronchitis.
AB  - Airway eosinophilia and cough may be associated with asthma and with non
      asthmatic eosinophilic bronchitis. Whether cough variant asthma and eosinophilic
      bronchitis are distinct entities or a pathophysiological spectrum needs further
      examination.

PMID- 14694254
TI  - Sleep. 1: Obstructive sleep apnoea/hypopnoea syndrome: definitions, epidemiology,
      and natural history.
AB  - Arguments over the definition of obstructive sleep apnoea/hypopnoea syndrome
      (OSAHS) have still not been satisfactorily resolved. As a result, robust
      estimates of the prevalence of OSAHS are not possible. New approaches are needed
      to identify those who have "CPAP responsive" disease, enabling more accurate
      estimates to be made of the prevalence of the sleep apnoea syndrome in the
      community.

PMID- 14694255
TI  - Multidrug resistant tuberculosis following lung transplantation: treatment with
      pulmonary resection.
AB  - Recipients of organ transplants are at increased risk for infection owing to
      their immunosuppressed state and the possibility of contamination of the donor
      organ. We report a case of multidrug resistant tuberculosis (MDR) transmission
      via a donor lung. After medical treatment with four drugs had failed, the patient
      underwent right upper lobectomy. There were no signs of disease on follow up more
      than 2 years later. To our knowledge, this is the first report of MDR
      tuberculosis in a lung transplant recipient. The need for a non-conservative
      approach, including pulmonary resection, to eradicate the infection is
      emphasised.

PMID- 14694256
TI  - Toll-like receptor (TLR) 4 polymorphisms and COPD.

PMID- 14694257
TI  - British guidelines on the management of asthma.

PMID- 14694258
TI  - Is there an association between impaired pulmonary function and mortality in
      never smokers?

PMID- 14694259
TI  - Peak flow meters still useful but require consistency rather than accuracy.

PMID- 14694260
TI  - Pneumocystis pneumonia in humans is caused by P jiroveci not P carinii.

PMID- 14694261
TI  - Adenocarcinoma of lung presenting with dysgeusia.

PMID- 14694262
TI  - Pulmonary artery aneurysm and tuberous sclerosis.

PMID- 14694263
TI  - Renal nerves mediate changes in contralateral renal blood flow after
      extracorporeal shockwave lithotripsy.
AB  - Renal blood flow falls in both kidneys following delivery of a clinical dose of
      shockwaves (SW) (2000 SW, 24 kV, Dornier HM3) to only one kidney. The role of
      renal nerves in this response was examined in a porcine model of renal
      denervation. Six-week-old pigs underwent unilateral renal denervation. Nerves
      along the renal artery of one kidney were identified, sectioned and painted with
      10% phenol. Two weeks later the pigs were anesthetized and baseline renal
      function was determined using inulin and PAH clearances. Animals then had either
      sham-shockwave lithotripsy (SWL) (group 1), SWL to the innervated kidney (group
      2) or SWL to the denervated kidney (group 3). Bilateral renal function was again
      measured 1 and 4 h after SWL. Both kidneys were then removed for analysis of
      norepinephrine content to validate the denervation. Renal plasma (RPF) flow was
      significantly reduced in shocked innervated kidneys (group 2) and shocked
      denervated kidneys (group 3). RPF was not reduced in the unshocked denervated
      kidneys of group 2. These observations suggest that renal nerves play a pivotal
      role in modulating the vascular response of the contralateral unshocked kidney to
      SWL, but only a partial role, if any, in modulating that response in the shocked
      kidney.

PMID- 14694264
TI  - Expression of visinin-like protein-3 in mouse kidney.
AB  - In renal proximal brush borders the Na/Pi cotransporter NaPi-IIa is part of a
      heteromultimeric complex including the PDZ proteins PDZK1 and NHERF1, which
      interact with the C terminus of NaPi-IIa. In this study, a yeast two-hybrid
      screen against the N terminus of the Na/Pi cotransporter NaPi-IIa was performed.
      Thereby we identified visinin-like protein-3 (VILIP-3), a member of neuronal
      calcium sensors. In this study, expression and protein localization of VILIP-3 in
      the mouse kidney was performed by immunofluorescence and RT-PCR using laser
      assisted microdissected nephron segments. VILIP-3 was found to be abundant in
      distal and collecting ducts where it partly colocalized with calbindin D28K. In
      addition VILIP-3 was observed in the brush borders of proximal tubular S1 and S3
      segments of both superficial and deep nephrons.

PMID- 14694265
TI  - Intervention with tranilast attenuates renal pathology and albuminuria in
      advanced experimental diabetic nephropathy.
AB  - BACKGROUND/AIMS: Tubulointerstitial pathology with the accumulation of
      extracellular matrix are pathological hallmarks of diabetic nephropathy that are
      directly related to declining renal function. Tranilast (N-[3,4
      dimethoxycinnamoyl]anthranilic acid), an inhibitor of transforming growth factor
      beta (TGF-beta), used to treat hypertrophic scars has recently been shown in
      pilot studies to exert a beneficial effect in advanced diabetic nephropathy in
      humans. However, its effects on diabetic renal pathology are unknown. METHODS:
      Studies were conducted using a transgenic model, the diabetic (mRen-2)27 rat,
      which develops many of the structural and functional characteristics of human
      diabetic nephropathy when diabetes is induced with streptozotocin (STZ). An
      experimental design was chosen to mimic, in part, the clinical context with drug
      therapy (tranilast 400 mg/kg/ day) initiated in established disease (8 weeks
      after STZ) and in the presence of persistent hyperglycaemia and hypertension.
      RESULTS: At 16 weeks, diabetes was associated with progressive albuminuria,
      tubulointerstitial fibrosis and tubular atrophy. Without affecting blood pressure
      or blood glucose, tranilast treatment was associated with a 83% reduction in
      tubulointerstitial fibrosis (p < 0.001), a 58% reduction in tubular atrophy (p <
      0.01) and near normalization of albuminuria (p < 0.05) in diabetic Ren-2 rats. In
      vitro studies in primary cultures of human renal cortical fibroblasts
      demonstrated a reduction in TGF-beta-induced hydroxyproline incorporation and
      fibronectin synthesis with tranilast 100 microM. CONCLUSION: Tranilast, when
      administered during the course of experimental diabetic nephropathy, attenuates
      tubulointerstitial pathology and albuminuria. These findings are consistent with
      the antagonist effects of tranilast on TGF-beta actions in the diabetic kidney.

PMID- 14694266
TI  - Cell biology of bladder development and the role of the extracellular matrix.
AB  - The bladder is unique. It is the most distensible organ in the body. If the
      normal pattern of development is disturbed, the bladder can become dysfunctional
      and poorly compliant. Renal outcome is intimately linked to bladder function and
      hence bladder development. In this review we describe our current knowledge of
      the molecular processes that govern bladder development, with particular emphasis
      on the role of the extracellular matrix. Finally, we suggest a hypothetical model
      for bladder development.

PMID- 14694267
TI  - Effect of vitamin E and vitamin C supplementation on antioxidative state and
      renal glomerular basement membrane thickness in diabetic kidney.
AB  - The aim of this study was to analyze the effect of vitamins C and E on
      malondialdehyde (MDA) content and activities of key antioxidant enzymes:
      superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)
      as well as glomerular basement membrane (GBM) thickness in streptozotocin-induced
      diabetic kidney in rats. Wistar male rats were divided into following groups (12
      rats each): the control, diabetic rats, diabetic rats whose drinking water was
      supplemented with vitamin C in a dose of 1.0 g/l or diet was supplemented with
      200 mg of vitamin E/100 g fodder. Body weight, blood glucose and HbA1C levels and
      24-hour urinary albumin excretion (UAE) were studied every week (0-12 weeks).
      After 6 and 12 weeks, MDA content and activities of SOD, CAT and GSH-Px were
      measured in the kidney homogenate supernatants. Electron micrographs of glomeruli
      were scanned and morphometric investigations were performed by means of computer
      image analysis system to compare GBM thickness. The blood glucose and HbA1C
      concentrations and UAE in diabetic rats were significantly higher than in the
      control group. An increase in the MDA level and decrease in the SOD, CAT and GSH
      Px activities in the kidney of diabetic rats were observed after 6 and 12 weeks
      of experiment. Administration of vitamins C and E did not affect body weight,
      blood glucose and HbA1C levels. Both vitamin C and vitamin E decreased lipid
      peroxidation and augmented the activities of antioxidant enzymes studied in the
      kidneys of diabetic rats as well as reduced UAE, decreased kidney weight and GBM
      thickness. The results indicate the potential utility of antioxidant vitamins in
      the protection against the development of diabetic nephropathy.

PMID- 14694268
TI  - Ultrastructure of tubular epithelial cells in response to microembolism-induced
      chronic ischemic injury in rats.
AB  - BACKGROUND: Loss of polarization of proximal tubular epithelial cells (PTECs)
      with detachment is known as an early response of PTEC to acute ischemia during
      acute tubular necrosis. However, the early morphologic changes of PTECs to
      chronic ischemic injury are not clear. We previously reported that rat renal
      microembolism induced chronic tubulointerstitial ischemia and extensive proximal
      tubular atrophy. Among atrophic tubules, some tubules showed a peculiar pattern
      mixed with intact and atrophic epithelial cells, which was thought to be the
      earliest feature leading to atrophic tubules. METHODS: Chronic ischemic injury
      was induced by the left renal perfusion of microspheres after removal of the
      right kidney in rats. The ultrastructual changes, especially focusing on the
      process of tubular atrophy, are examined by electron microscopy after 4, 8 and 12
      weeks. RESULTS: Early changes in PTECs showed slight simplification or
      dedifferentiation such as loss or diminution of basolateral infolding and
      microvilli. Moderately simplified PTECs were partially detached from the tubular
      basement membrane (TBM) with matrix production in the detached spaces but
      maintained cell-cell contacts between PTECs. In the advanced stage, severely
      simplified PTECs showed complete detachment from TBM and more atrophic features
      characterized by cobblestone appearance with a uniform attachment between cells.
      In concert with these PTEC changes, accumulation of interstitial fibroblast-like
      cells (FLCs) with collagenous matrices could be found first in the interstitial
      spaces and later in the spaces where PTECs detached from TBM. CONCLUSION: Our
      results suggest that microembolism-induced chronic ischemic injury induces PTEC
      dedifferentiation and detachment from TBM with matrix production in concert with
      FLC activation, resulting in tubulointerstitial damage characterized by tubular
      atrophy and renal fibrosis.

PMID- 14694269
TI  - Microfocus computed tomography analysis of early changes in bone microstructure
      in rats with chronic renal failure.
AB  - BACKGROUND/AIMS: Little is known about the microstructural changes in bone tissue
      in the early phase of chronic renal failure (CRF). In this study, we analyzed the
      bone tissue in a rat model of early CRF using a high-resolution X-ray tomographic
      system, i.e. microfocus computed tomography (MXCT), which is capable of detecting
      microscopic structural changes in bone tissue. METHODS: CRF rats were created by
      7/8 nephrectomy by ligation of the renal artery branches, and were sacrificed 24
      weeks after surgery. MXCT and bone mineral densitometry by single-energy X-ray
      absorptiometry (SXA) were performed using extracted bone samples. Images obtained
      by MXCT were further analyzed by node-strut morphometry. RESULTS: Biochemical
      analysis confirmed that CRF was induced in 7/8-renal artery-ligated rats. MXCT
      demonstrated a significant decrease in trabecular bone in uremic rats, whereas
      SXA was unable to detect the difference. The node-strut method revealed decreased
      trabecular connectivity, with little change in the thickness of the trabecular
      bone in uremic rats. CONCLUSION: MXCT was able to detect significant changes in
      trabecular bone at an early stage of renal failure. The observed structural
      changes differed from those found in long-term dialysis patients. MXCT is a
      practical and promising device used for the non-invasive evaluation of early bone
      changes in uremic patients.

PMID- 14694270
TI  - Statins in chronic kidney disease: effective anti-inflammatory agents?

PMID- 14694271
TI  - Therapeutic considerations for the use of statin therapy in chronic renal
      disease.
AB  - This review presents an evidence-based analysis of the use of 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitors (statins) in patients with chronic
      renal disease. It considers the characteristics and incidence of dyslipidaemia
      among specific patient types and describes the available data concerning the
      ability of statin therapy to regulate dyslipidaemia in the renal disease
      population as well as early results for an anti-inflammatory effect in this
      group. The clinical impact of statins in terms of reduced morbidity and mortality
      is also discussed. The relative merits of different statin agents are reviewed in
      terms of efficacy and safety, together with the role of aggressive intervention
      as compared with standard approaches to care. Finally, a proposed algorithm for
      the initiation and monitoring of statin therapy in chronic renal disease patients
      is presented.

PMID- 14694272
TI  - Increased urinary protein excretion in children from families with balkan endemic
      nephropathy.
AB  - BACKGROUND: Balkan endemic nephropathy (BEN) has not been described in children,
      however some previous studies of children from families with BEN have revealed
      abnormalities of the urinary tract including an increased urinary protein
      excretion. METHODS: In the present study, urinary excretion of total protein was
      studied in 703 healthy children, aged 9-13, from endemic and non-endemic
      settlements around the South Morava River. Since BEN is an environmentally
      induced disease, with possible seasonal variation of toxin(s), children were
      studied three times a year: in spring, autumn and winter, during a 3-year period.
      After a water load of 15 ml/kg body weight, a 3-hour urine sample was collected,
      from 7 to 10 a.m. RESULTS: Protein excretion in urine was highest in children
      from families with BEN compared with the excretion in children from the city, non
      endemic villages, and those from non-endemic families living in the same
      settlements. This was the case during all three periods investigated in the
      second year of the study. In the autumn term of all three years of the study,
      protein excretion was significantly higher in children from families with BEN
      than in children from the city and from non- endemic families living in the same
      settlements. If the upper limit of protein excretion is set at 34 mg/mmol
      creatinine, then increased protein excretion in autumn was found in the first
      year of study in 9/229 children from endemic settlements and in only 4/474
      children from non-endemic areas (p = 0.004); in the second year in 5/229 and
      3/474 children (p = 0.069), and in the third year in 10/229 and 4/474 children (p
      = 0.002), respectively. CONCLUSIONS: We have presented evidence that children
      from families with BEN and endemic villages consistently excreted significantly
      more protein in the autumn, and in three seasons (spring, autumn, winter) in 1
      year of our study. These results are consistent with seasonal variations in
      exposure to an environmental toxin(s).

PMID- 14694273
TI  - Calcitriol increases burst-forming unit-erythroid proliferation in chronic renal
      failure. A synergistic effect with r-HuEpo.
AB  - BACKGROUND: Calcitriol (C) improves anemia in chronic renal failure. This effect
      may be related to the suppression of iPTH release, or to a direct effect on
      erythropoiesis. METHODS: Thirty-three patients with chronic renal failure were
      enrolled; among them, 24 were on chronic hemodialysis and 9 on conservative
      management. None had other chronic or hematological disease, aluminum levels were
      below 20 microg/l and DFO testing was negative. The iPTH range was 250-480 pg/l.
      None were treated with C or r-HuEpo. In vitro study: Samples were drawn for a
      basal erythroid precursor (burst forming unit-erythroid BFU-E) study: Mononuclear
      cells were incubated for 14 days with r-HuEpo 3U/ml (A), r-HuEpo 3U/l + C 30 pg
      (B), r-HuEpo 3U/ml + C 300 pg (C), or r-HuEpo 30 U/ml + C 300 pg (D). In vivo
      study: After the basal evaluation, 10 patients on chronic dialysis were treated
      with C (Calcijex-Abbott) 1 microg three times a week, and 4 patients served as
      controls. BFU-E studies were performed after 1, 2 and 4 months. RESULTS: In
      vitro, culture B showed increased BFU-E proliferation vs. A (41 +/- 23 vs. 27 +/-
      15, p < 0.02); in cultures C and D, proliferation was 61 +/- 31 and 78 +/- 42,
      respectively, p < 0.01 vs. A. There was no difference among patients with
      predialysis renal failure and those on dialysis. BFU-E proliferation was
      inversely related to basal Hb (p < 0.04) and CRP levels (p < 0.05). During the in
      vivo study, all cultures showed a progressive increase in proliferation without a
      plateau level (basal, after 1, 2 and 4 months, respectively) In A: 17 +/- 8, 22
      +/- 13, 30.9 +/- 14.9, 41.4 +/- 20; in B: 27.3 +/- 15, 35.6 +/- 20, 45.5 +/- 21,
      57 +/- 26; in C: 48.2 +/- 20.6, 63.7 +/- 32, 75.7 +/- 37, 83 +/- 40; in D: 72 +/-
      24, 91 +/- 42, 106 +/- 42, 110 +/- 42.3 (all p < 0.001). Hb and Hct showed a
      significant increase (p < 0.03) in the treatment group. The decrease in iPTH was
      not related to BFU-E proliferation. CONCLUSIONS: In chronic uremia, C has a
      direct effect on erythroid precursors proliferation, as demonstrated both in
      vitro and in vivo, with a synergistic effect with r-HuEpo. C may be a useful
      adjuvant therapy to r-HuEpo treatment.

PMID- 14694275
TI  - The ischemic penumbra: identification, evolution and treatment concepts.
AB  - The concept of the ischemic penumbra is an important one for both basic
      investigators of cerebral ischemia and for clinicians who treat stroke patients.
      The ischemic penumbra has been defined in a variety of ways, but the most
      clinically relevant definition is that portion of the ischemic territory that is
      still potentially salvageable, if an appropriate treatment is given. Currently,
      three main challenges persist for those interested in the ischemic penumbra
      concept: how can this ischemic region be most accurately identified in stroke
      patients, what mechanisms of ischemic cell death are most important for
      progression from penumbra towards irreversible injury and what therapeutic
      modalities are most likely to impede the development of infarction? Much
      important information regarding each of these topics has become available
      recently and will be the focus of this paper.

PMID- 14694274
TI  - Effects of atorvastatin on lipid profile and non-traditional cardiovascular risk
      factors in diabetic patients on hemodialysis.
AB  - BACKGROUND/AIMS: Dyslipidemia and non-traditional cardiovascular (CV) risk
      factors, such as lipoprotein(a) (Lp(a)), homocysteine, oxidative stress and
      inflammation, are important determinants in the increased CV risk of hemodialysis
      (HD) patients. The aim of our study was to evaluate the effects of atorvastatin
      on these parameters in one of the groups with the highest CV risk: diabetic
      patients with end-stage renal disease under HD therapy. METHODS: Twenty
      maintenance HD diabetic patients (mean age 64 +/- 10 years, mean time on HD 25 +/
      11 months) with low-density lipoprotein cholesterol (LDL-C) >2.59 mmol/l
      received atorvastatin (10 mg/day) for 4 months. Lipid profile, including total
      cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C),
      triglycerides (TG), apolipoproteins A1 and B (Apo-A and Apo-B), and the non
      traditional risk factors Lp(a), homocysteine, autoantibodies against oxidized LDL
      C (anti-LDLox), total antioxidant status (TAS), and high sensitive C-reactive
      protein (hs-CRP), were measured at baseline and at the end of the study. Safety
      was assessed by clinical and laboratory (liver and muscle enzymes) monitoring
      once a month. RESULTS: Mean percent reductions for TC, LDL-C and TG were 18.5% (p
      < 0.001), 22% (p < 0.001) and 19% (p < 0.01), respectively. The ratios of TC/HDL
      C and LDL-C/HDL-C decreased after treatment (p < 0.05), whereas the ratios of LDL
      C/Apo-B (p < 0.01) and Apo-A/Apo-B (p < 0.001) increased. No significant changes
      were observed in HDL-C. Concerning the non-traditional risk factors, levels of
      homocysteine, Lp(a), anti-LDLox and TAS did not change significantly. However, hs
      CRP decreased from 5.4 (range 0.9-67.8) to 2.3 mg/l (range 0.4-21) (p < 0.01),
      whereas a concomitant increase in serum albumin was observed (from 38 +/- 2 to 40
      +/- 1.7 g/l, p < 0.01). At baseline, hs-CRP was inversely associated with HDL-C
      and Apo-A, and directly related to Lp(a). The change in hs-CRP was inversely
      associated with the change of HDL-C, whereas a direct correlation was found with
      the change of TG. CONCLUSIONS: Atorvastatin administration to diabetic patients
      on HD is associated with improvement of lipid profile and reduction of hs-CRP.
      These effects may be critical for the reduction of CV risk and mortality in HD
      population.

PMID- 14694276
TI  - Biochemical changes and inflammatory response as markers for brain ischaemia:
      molecular markers of diagnostic utility and prognosis in human clinical practice.
AB  - The study of molecular markers associated with stroke has proved to be of
      considerable utility. We review the main biochemical changes of neurotoxicity and
      of inflammation and their usefulness as markers associated with early signs of
      ischaemia in the neuroimage, with early neurological deterioration, with the
      volume of the infarct, with haemorrhagic transformation, with the efficacy of
      thrombolytic treatment and with malignant ischaemic syndrome. Raised plasma
      concentrations of interleukin-6 (IL-6) are a powerful predictor of early
      neurological deterioration and the more important molecular marker associated
      with final volume of infarct. Levels of matrix metalloproteinases-9 (MMP-9) have
      a significant relationship with the efficacy of thrombolytic treatment and with
      the incidence and seriousness of haemorrhagic complications.

PMID- 14694278
TI  - Continuous recording of blood pressure in cerebrovascular disease: when should it
      be done?
AB  - BACKGROUND AND OBJECTIVES: Ambulatory blood pressure (BP) monitoring has found
      some specific clinical indications in the treatment and control of hypertension
      (HT). As with other target organs exposed to vascular damage dependent on HT,
      ambulatory BP monitoring can be a useful tool in the prevention of
      cerebrovascular processes. METHOD: Review of published articles (Medline
      database) which have investigated the value of continuous recording of BP in
      cerebrovascular disease (CVD). RESULTS: Research on the BP patterns and its
      relationship with stroke has been carried out in subjects with no previous
      history of CVD (cohort studies and in patients with essential HT, differentiating
      between adults and elderly patients) and patients after a cerebral ischemic
      event. The study objectives are aimed at determining its prognostic value in the
      development of silent and symptomatic CVD, and its prognostic significance
      regarding functional recovery and the differences of the BP patterns according to
      the different stroke subtypes. CONCLUSIONS: BP monitoring is a useful technique
      with applications in the control and treatment of the pathological variations of
      BP in hypertensive patients, with and without a previous history of cerebral
      ischemia, and mainly in elderly patients, due to the deterioration of the
      cerebral circulation regulation mechanisms. Clinical research has confirmed the
      importance of factors related to the circadian rhythm of BP in the primary and
      secondary prevention of cerebrovascular processes.

PMID- 14694277
TI  - Ultrasound and arterial wall disease.
AB  - Rapid progress in non-invasive ultrasound techniques has resulted in a wide
      variety of clinical applications for the assessment of cerebrovascular diseases.
      Recent highlights in ultrasound research include the evaluation of vascular
      ageing as a degenerative process, the demonstration of plaque development, motion
      and vulnerability in atherosclerosis and multi-dimensional as well as innovative
      imaging techniques (e.g., compound imaging) to depict early and small vascular
      lesions. In addition, echo-contrast agents have been used to compensate for
      difficulties in visualising late, severe or subtotal obstructive plaques, but
      failed to be really superior to conventional techniques as evidenced in a
      prospective, multi-centre trial (Contrast Enhanced Duplex sonography versus
      Arteriography Studies - CEDAS). With increasing sophistication of ultrasound
      methodology, it becomes essential to establish standards for data acquisition and
      interpretation: three consensus meetings have provided detailed recommendations
      on quantification of carotid atherosclerosis, characterisation of carotid artery
      plaques and detection of microembolism by transcranial Doppler as a potential
      indicator of stroke risk.

PMID- 14694279
TI  - Cerebral ischemia: new risk factors.
AB  - Stroke is a disease with well-defined modifiable risk factors such as arterial
      hypertension, smoking, diabetes, hyperlipidemia and atrial fibrillation. The need
      of new risk factors is based on the fact that only half the cardiovascular
      disease risk is explained by conventional risk factors. Inflammatory markers,
      infection, homocysteine and sleep-disordered breathing rank as the four most
      important new risk factors in cerebral atherosclerosis. C-reactive protein is the
      inflammatory marker that has been most thoroughly studied. Elevated
      concentrations of C-reactive protein increase the risk of heart disease and
      thromboembolic stroke in men and women. The role of Chlamydia pneumoniae is still
      controversial. Influenza vaccination is a simple and effective preventive measure
      against stroke. Despite the potential relationship between homocysteine and
      stroke, we should wait to the results of the ongoing trials to know if the
      reduction of homocysteine levels with vitamin therapy is of clinical benefit.
      Sleep-disordered breathing is a potential new risk factor with an effective
      therapy. Neurologists should not forget to look for sleep disorders in their
      stroke patients and probably manage them with breathing therapy from the acute
      phase.

PMID- 14694280
TI  - High blood pressure as risk factor and prognostic predictor in acute ischaemic
      stroke: when and how to treat it?
AB  - High blood pressure is common in the western world and is a major risk factor for
      the development of stroke. Lowering blood pressure reduces the risk of first and
      recurrent stroke. High blood pressure is also common in acute stroke and is
      independently associated with a poor prognosis, in part due to promoting early
      recurrence and the development of fatal cerebral oedema in patients with
      ischaemic stroke and, possibly, re-bleeding in those with haemorrhagic stroke.
      However, the management of blood pressure remains an enigma--its lowering could
      improve outcome by reducing recurrence or worsen outcome by reducing regional
      perfusion in the face of dysfunctional cerebral autoregulation. Conversely,
      raising blood pressure might improve outcome by raising regional perfusion or
      worsen it by inducing cerebral oedema and early recurrence. Administration of
      some vaso-active drugs (beta-receptor antagonists and calcium channel blockers)
      can worsen outcome and reduce cerebral blood flow. In contrast, other drug
      classes--angiotensin- converting enzyme inhibitors, angiotensin receptor
      antagonists and nitrates--appear to lower blood pressure without reducing
      measures of cerebral perfusion. In the absence of definitive trial data, which is
      urgently needed, blood pressure should not be routinely lowered unless it is
      extreme (systolic blood pressure >220 mm Hg) or associated with arterial
      dissection or cardiac ischaemia or failure, in which case cautious lowering
      (<15%), perhaps with an angiotensin-converting enzyme inhibitor, angiotensin
      receptor antagonist or nitrate, is appropriate.

PMID- 14694281
TI  - New concepts in lacunar stroke etiology: the constellation of small-vessel
      arterial disease.
AB  - OBJECTIVE: To update the less frequent etiologies causing lacunar infarcts (LIs).
      To highlight recent advances in risk factors, clinical syndromes, topography,
      complementary tests and long-term prognosis in this subtype of ischemic stroke.
      PATIENTS AND METHODS: The most important studies are analyzed, from CM Fisher
      works, selecting those referring to LIs of unusual etiology, and recent advances
      and controversies in the clinical management of LI are discussed. RESULTS: LIs
      are found in approximately 11% of patients admitted with stroke. The pure motor
      hemiparesis (55%) constitutes the most usual lacunar syndrome. However, lacunar
      syndromes may not be caused by LIs in 10-20% of cases. LIs caused by
      microembolism and cholesterol embolism from the aortic arch are reviewed.
      Hematological diseases can also cause LI, such as polycythemia rubra vera,
      essential thrombocythemia and primary antiphospholipidic antibody syndrome. Other
      etiologies are carotid plaque embolism, severe stenosis of a perforated arteriole
      and amyloid angiopathy. Infectious arteritis by neurolues, neurocysticercosis,
      neuroborreliosis, by AIDS or Helicobacter pylori infection have also been
      associated with the presence of LIs. Likewise, inflammatory arteritis in systemic
      lupus erythematosus or granulomatous angiitis, cocaine abuse and panarteritis
      nodosa have been related to LI, although in the latter LI would be caused by a
      thrombotic microangiopathy and not by vasculitis. CONCLUSIONS: LI is an ischemic
      stroke subtype with a characteristic clinical presentation and a short-term
      favorable prognosis. Although high blood pressure constitutes the main risk
      factor and the main etiology, LIs may be caused, in less than 5% of cases, by
      various etiologies, mainly hematological diseases and infectious or inflammatory
      arteritis. It is essential to make a correct etiological diagnosis for LI as
      treatment will be different according to its etiology.

PMID- 14694282
TI  - A genetic approach to ischemic stroke therapy.
AB  - Stroke therapy will undergo a great revolution in the present decade. The
      knowledge of the human genome, gene interactions and proteomics will permit a new
      concept of drug development for stroke. Gene therapy by modification of gene
      expression will be useful to treat atherosclerosis and hypertensive
      microangiopathy, or in the acute phase, we will manipulate the acute gene
      expression induced by ischemia or the apoptotic gene program. However, a single
      abnormal gene, as in monogenic diseases, is easier to replace than several genes
      in complex multigenic disorders. Gene therapy, stem cell therapy and neurological
      grafts for stroke are still in the experimental phase, and many hurdles will have
      to be jumped before the introduction of these therapies into human clinical
      stroke trials. A more immediate clinical application of genetics to stroke
      therapy is the development of pharmacogenetics that analyzes the influence of
      genetic variability of individuals on drug response. A new era of personalized
      therapy is dawning where specific DNA biochips will help stroke clinicians to
      decide on the better use of thrombolytics, neuroprotectants, antithrombotics,
      statins or antihypertensives.

PMID- 14694283
TI  - Usefulness of anticoagulants in the prevention of ischemic stroke.
AB  - Oral anticoagulants are drugs commonly used in the prevention of vascular
      diseases, especially in embolic-type processes. Although several studies have
      assessed the possibility of using them in arterial processes, the experience has
      not been satisfactory so far. Heart diseases with major emboligenic flow are
      still the main indication, while the prevention of other low-risk heart diseases
      and treatment of large- or small-artery disease can be based on antiaggregant
      treatment. Other groups study the problem in large series.

PMID- 14694284
TI  - Antiplatelet drugs in ischemic stroke prevention: from monotherapy to combined
      treatment.
AB  - Aspirin (acetylsalicylic acid) is the most widely studied and prescribed
      antiplatelet drug for patients at high risk of vascular disease. It affects a
      single pathway in the platelet activation process and provides incomplete
      protection against cardiovascular events. Adenosine diphosphate receptor
      antagonists, by blocking an alternate pathway of platelet activation, are
      slightly more effective than aspirin in reducing serious vascular events in
      patients at high risk, with similar results for the subset of transient ischaemic
      attack/ischaemic stroke patients. Clopidogrel is an effective and safe
      alternative in patients who do not tolerate aspirin, in diabetics, in
      hypercholesterolaemic patients, or in those with a previous history of cardiac
      surgery. Moreover, antiplatelet combination therapy using agents with different
      mechanisms of action is an attractive preventive approach. In this way,
      dipyridamole combined with aspirin is being tested in the European/Australian
      Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) in cerebrovascular
      disease patients. Clinical and preclinical studies have demonstrated that therapy
      with clopidogrel and aspirin provides synergistic antiplatelet effects. The
      Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and PCI-CURE
      trials demonstrate the benefit of this combination therapy in patients who suffer
      from unstable angina or non-Q-wave myocardial infarction treated or not by
      percutaneous coronary intervention. The relative risk reduction in ischaemic
      events in long-term use was 20%. This antiplatelet regimen was safe and well
      tolerated. Currently, this therapeutic option is tested in individuals with
      ischaemic stroke in the Management of Atherothrombosis with Clopidogrel in High
      Risk Patients with Recent Transient Ischaemic Attacks or Ischaemic Stroke (MATCH)
      Trial.

PMID- 14694285
TI  - Statins and stroke prevention.
AB  - Four randomized trials with a statin and one trial with a fibrate showed a modest
      but significant absolute reduction in the incidence of stroke in patients with a
      previous myocardial infarction. The reasons for the positive effect of statins on
      stroke end-point are unclear since, paradoxically, the link between serum
      cholesterol level and stroke has never been fully established. Furthermore, the
      positive results of statins trials were mainly obtained in patients with an
      average or a low serum cholesterol level. This suggests nonhypolipidemic effects
      of these drugs, so-called pleiotropic effects, acting on the biologic promoters
      of plaque instability. Statins have a good overall safety profile with no
      increase of hemorrhagic stroke and no increase in cancer. They have positive
      effects in primary prevention of cardiovascular disease in high-risk young as
      well as elderly populations. Statins reduced stroke incidence in high-risk
      (mainly CHD, diabetics and hypertensives) population even with a normal baseline
      blood cholesterol level, which argues for a global cardiovascular risk-based
      treatment strategy. In patients with prior strokes, statins likely reduce the
      incidence of cononary events, but it is not yet proven that statins actually
      reduce the incidence of recurrent strokes in secondary prevention. If current
      hypotheses are verified by ongoing trials, we may expect between 20 to 30 more
      stroke events avoided per 1,000 patients treated during 2 years with a lipid
      lowering agent, which adds to the 28 stroke events prevented with an antiplatelet
      agent over the same time period. This would be one of the most significant
      advances in stroke and vascular dementia prevention since the era of aspirin
      therapy.

PMID- 14694286
TI  - Effective stroke prevention in patients with symptomatic carotid stenosis.
AB  - Patients with recently symptomatic carotid stenosis require effective medical
      treatment, and some require surgical removal of the carotid plaque. Randomized
      controlled trials have shown that endarterectomy reduces the overall risk of
      stroke in patients with severe carotid stenosis and, to a lesser extent, in
      patients with moderate stenosis. However, operating on all patients is not
      necessarily the most effective approach. The effectiveness of endarterectomy
      could be improved by selecting patients more rigorously. To do this, we first
      need to use data from existing randomized controlled trials to precisely
      determine the overall effect of surgery for different degrees of stenosis,
      identify subgroups in which benefit is increased, and use risk modeling to
      identify individuals at particularly high risk of stroke without surgery. Such an
      approach will also be useful in targeting angioplasty and stenting in patients in
      whom endarterectomy is not possible.

PMID- 14694287
TI  - Internal carotid artery stenting in patients with symptomatic atheromatous pseudo
      occlusion.
AB  - Angioplasty and stenting of the atheromatous internal carotid artery (ICA),
      besides in patients with a high surgical risk, may be indicated in specific cases
      such as contralateral occlusion, acute stroke clinical signs, or atherosclerotic
      pseudo-occlusion (APO). APO of the ICA is an underrecognized condition due to
      diagnostic difficulties both with noninvasive methods and even with angiography.
      Once recognized, there is usually the opportunity for successful
      revascularization with carotid endarterectomy. However, as the natural history of
      the APO is poorly characterized, the management of patients remains
      controversial. While some authors advocate a surgical approach, others consider
      that APO patients are not at high risk of stroke, making any interventional
      approach unnecessary. The perioperative risk of stroke in patients with APO is
      not appreciably greater than in patients with lesser degrees of stenosis and
      clear recommendation of surgery, although at 2 years that risk seems to be
      considerably much higher than in the latter patients. Looking for safer
      interventional procedures is worthwhile. Results of angioplasty and stenting in
      patients with ICA-APO have not been published yet. We report the results and
      complications associated with this procedure to address the issue of appropriate
      management of patients with ICA-APO.

PMID- 14694288
TI  - Organization of medical care in acute stroke: importance of a good network.
AB  - Stroke is a medical emergency which requires hospital care. Therapeutic and
      effective organizative measures, such as thrombolysis and stroke units, are
      available, but early attention is required, as the benefits are time dependent
      (therapeutic window). To achieve this objective, a high level of organization and
      coordination is required between the various steps of care. The chain of
      attention in acute stroke (from symptom onset till stroke unit admission) is a
      complex process. The main points are reviewed: delay in attention, knowledge and
      attitude towards stroke, emergency transportation, neurological attention,
      educational campaigns, clinical protocols and pathways, stroke codes, and
      existing resources for care. The organization must be modified to have the
      resources for care necessary for attending acute stroke available, if we want to
      achieve the real objective of maximum benefit for our patients as set out in the
      Declaration of Helsingborg.

PMID- 14694289
TI  - The cost of stroke.
AB  - The control of health expenditure has become one of the main axes of health
      policy. Cost studies are an indispensable tool for determining the economic
      impact of disease and for assigning the material and human resources required for
      the prevention, diagnosis, treatment, and follow-up of patients with different
      diseases. Cost studies in stroke are necessary due to the increasing incidence of
      this disease which represents a significant cause of death and invalidity in
      adults and produces important hospital and social spending, and for which
      patients must be treated in specialized units (stroke units). The principal cost
      determining factors in most studies are those generated by hospital admission
      (principally hospital stay). Other cost-determining factors include severity,
      stroke subtype or the fate of patients on discharge. Future health policies aimed
      at optimizing economic resources must be directed towards reducing hospital stay
      and minimizing patient disability.

PMID- 14694290
TI  - Acute care in stroke: the importance of early intervention to achieve better
      brain protection.
AB  - It is known that 'time is brain', and only early therapies in acute stroke have
      been effective, like thrombolysis within the first 3 h, and useful
      neuroprotective drugs are searched for that probably would be effective only with
      their very early administration. General care (respiratory and cardiac care,
      fluid and metabolic management, especially blood glucose and blood pressure
      control, early treatment of hyperthermia, and prevention and treatment of
      neurological and systemic complications) in acute stroke patients is essential
      and must already start in the prehospital setting and continue at the patient's
      arrival to hospital in the emergency room and in the stroke unit. A review of
      published studies analyzing the influence of general care on stroke outcome and
      the personal experience from observational studies was performed. Glucose levels
      >8 mmol/l have been found to be predictive of a poor prognosis after correcting
      for age, stroke severity, and stroke subtype. Although a clinical trial of
      glucose-insulin-potassium infusions is ongoing, increased plasma glucose levels
      should be treated. Moreover, insulin therapy in critically ill patients,
      including stroke patients, is safe and determines lower mortality and
      complication rates. Both high and low blood pressure levels have been related to
      a poor prognosis in acute stroke, although the target levels have not been
      defined yet in clinical trials. The body temperature has been shown to have a
      negative effect on stroke outcome, and its control and early treatment of
      hyperthermia are important. Hypoxemia also worsens the stroke prognosis, and
      oxygen therapy in case of <92% O(2) saturation is recommended. Besides, blood
      pressure stabilization avoiding falls of the diastolic pressure and the lowering
      of glycemia and temperature have been related to a better prognosis in stroke
      units patients, and homeostasis maintenance is associated with a better outcome.
      General care has become an emergent and first-line brain-protectant treatment
      that must be started at the prehospital level from the very beginning. This could
      help to save more brain tissue to get the best conditions for further specific
      stroke therapies such as the use of neuroprotective or thrombolytic drugs in the
      hospital.

PMID- 14694291
TI  - Antithrombotic and hypofibrinogenetic therapy in acute ischemic stroke: what is
      the next step?
AB  - A thrombus occluding a brain artery is the leading mechanism underlying ischemic
      stroke. In the light of this pathophysiology, antithrombotic therapies have been
      among the most widely studied and used in the management of patients with
      ischemic stroke. Aspirin has a significant but modest benefit by reducing
      recurrent ischemic stroke and death given within 48 h of stroke onset. The use of
      anticoagulants including heparin, low molecular weight heparin, and heparinoids
      has not been supported by results of randomized clinical trials. Any reductions
      in ischemic stroke recurrence were offset by an increase in major bleeding.
      However, acute anticoagulation is widely used in specific disorders, including
      patients with high-risk cardiac sources of embolus, arterial dissection, venous
      sinus thrombosis, and hypercoagulable states. Early recurrent ischemic strokes in
      patients with atrial fibrillation and acute ischemic stroke have not been shown
      to be reduced with the heparins, when the effects of major bleeding and
      hemorrhagic worsening are considered. Recent clinical trials have suggested that
      other antithrombotic agents may be beneficial in acute ischemic stroke. Two such
      agents are ancrod and abciximab. Abciximab is currently being investigated in a
      large randomized clinical trial.

PMID- 14694292
TI  - Thrombolysis: from the experimental findings to the clinical practice.
AB  - Antithrombotic strategies have provided the most benefit to patients with
      ischemic stroke. Of these, the acute use of recombinant tissue plasminogen
      activator (rt-PA) has been shown to significantly increase the number of patients
      who suffer little or no residual disability. Experimental work indicated that
      early reperfusion of occluded brainsupplying arteries reduces the size of injury
      and improves outcome in several species. However, there has been little progress
      to increase the proportion of patients who are benefitted by acute intervention
      with PAs since the initial report. Clinical trial experience highlights
      limitations in a number of aspects of design and outcome which suggest
      refinements for future trials. Experimental work suggests that improved outcome
      is also possible with acute intervention using other antithrombotic agents. There
      is considerable opportunity to explore safe strategies which could further
      benefit stroke outcome.

PMID- 14694293
TI  - Neuroprotection in cerebral ischaemia: facts and fancies--the need for new
      approaches.
AB  - 'Neuroprotection' is a term used to describe the putative effect of interventions
      protecting the brain from pathological damage. In occlusive stroke, the concept
      of neuroprotection involves inhibition of a cascade of pathological molecular
      events occurring under ischaemia and leading to calcium influx, activation of
      free radical reactions and cell death. This article will summarize
      neuroprotection trials to date, some facts and fancies about neuroprotection,
      ischaemic pathophysiology and possible reasons for the apparent failure of human
      neuroprotective stroke trials. FACTS: In the acute stage of occlusive stroke,
      moderate reduction of blood flow results in a 'penumbra' of brain cells, often
      surrounding a core infarct, in which brain cells survive for a few hours but
      gradually die if reperfusion is not established. Increased knowledge of the
      complex pathophysiology in acute ischaemic stroke has led to the development of a
      great number of candidates for neuroprotective interventions. Many
      neuroprotective agents have proven efficacious in animal models, but so far no
      human study has shown a statistically significant benefit in patients with acute
      ischaemic stroke on primary endpoint measures. Some neuroprotective agents show
      beneficial effects on post hoc analyses, and some studies are still ongoing.
      FANCIES: In the early years of neuroprotective studies in stroke, it was thought
      that a drug with almost no adverse effects could be given by ambulance staff on
      the way to hospital and induce a clinically significant effect on outcome. Since
      there were only benefits and no risks, diagnostic skills by neurologists and
      neuroradiological evaluations would no longer be required. WHY HAVE
      NEUROPROTECTIVE AGENTS FAILED IN HUMAN STROKE TRIALS? There are several possible
      explanations why neuroprotective trials have been unable to prove an effect in
      addition to the eventuality that the basic concept is wrong. The effects of
      neuroprotective agents on infarct size are time dependent, and treatment has
      often been initiated much later than in successful experimental stroke models.
      Insufficient doses of the drugs and slow availability of the drug at the target
      area may be other explanations. Too small sample sizes in trials and imbalance of
      prognostically important baseline variables are examples of shortcomings in trial
      methodology. WHAT CAN BE DONE? FUTURE NEW APPROACHES: IN ANIMAL MODELS,
      preclinical testing of neuroprotective candidates should be standardized.
      Conventional stroke models with young and healthy animals may be replaced by
      older animals with common co-morbidity such as atherosclerosis. Highly effective
      new neuroprotective agents need to be discovered, and combination therapies
      should be tried. IN CLINICAL TRIALS, the greatest chances of success may be with
      neuroprotective concepts involving mechanisms in both ischaemic and reperfusion
      pathophysiology, in combination with a thrombolytic therapy protocol.
      Neuroprotective agents, possibly combinations of agents, should preferably
      approach several of these mechanisms. Treatments should be initiated early, at
      least within 3 h after stroke onset, by an intravenous route. The selected
      compound(s) should easily pass the blood-brain barrier. Neuroprotective agents
      shown to be highly effective in stroke models should be preferred, and doses used
      experimentally should be used also in the clinical setting. Trials should use
      randomization techniques, which reduce imbalances of prognostically important
      baseline variables, and the estimated sample size of a trial should be based on
      expectations of a modest clinical effect.

PMID- 14694294
TI  - Addressing the "general competencies": what is this all about?

PMID- 14694295
TI  - Why the 6 general competencies?

PMID- 14694296
TI  - Assessing competency in surgery: where to begin?

PMID- 14694297
TI  - Development and validation of a comprehensive program of education and assessment
      of the basic fundamentals of laparoscopic surgery.

PMID- 14694298
TI  - Using simulators to assess laparoscopic competence: ready for widespread use?

PMID- 14694299
TI  - Invited commentary: Educational interventions to address the core competencies in
      surgery.

PMID- 14694300
TI  - Effects of surgical treatment of the metabolic syndrome on liver fibrosis and
      cirrhosis.
AB  - BACKGROUND: Both weight loss and gastrointestinal surgery for obesity can cause
      liver disease, making their role in the treatment of obesity-related liver
      disease controversial. METHODS: Six hundred eighty-nine severely obese women
      (n=551) and men (n=138), BMI=47+/-9 kg.m(-2) (mean+/-SD), without known liver
      disease, underwent biliopancreatic diversion (BPD) with liver biopsy. Fourteen
      patients (2%) had cryptogenic cirrhosis, 11 of whom underwent multiple repeat
      biopsies. After 38+/-18 kg weight loss, 104 of the 689 patients underwent routine
      second biopsies during reoperations 41+/-25 months after BPD. All biopsy
      specimens were graded for steatosis, fibrosis, and inflammation by a blinded
      hepatopathologist. RESULTS: All 689 patients lost weight accompanied by
      improvements in the metabolic syndrome. Among the 104 patients who underwent
      reoperation, severe fibrosis (grade 3-5) decreased in 28 whereas mild fibrosis
      (grade 1-2) appeared in 42. Increased fibrosis was related to low-normal serum
      albumin, uncontrolled diarrhea, low intake of alcohol, and menopausal status.
      Fibrosis and inflammation decreased over time (P<.01). The 11 patients with
      cirrhosis exhibited decreased fibrosis from a mean grade 5 to grade 3, as well as
      reduced inflammation, Mallory bodies, and glycogenated nuclei. Seven patients had
      disappearance and 2 regression of nodules and fibrous bridging. CONCLUSIONS: The
      metabolic syndrome of obesity is a determinant of liver fibrosis and cirrhosis,
      treatable by substantial weight loss after malabsorptive surgery.

PMID- 14694301
TI  - Malignant fibrous histiocytoma of the extremities and trunk: an institutional
      review.
AB  - BACKGROUND: Malignant fibrous histiocytoma (MFH) is the most common subtype of
      soft-tissue sarcoma. Detailed understanding of this tumor type may lead to
      improved therapeutic strategies. METHODS: An institutional review was performed
      on all patients with primary MFH of the extremities and trunk operated on between
      1988 and 2000. RESULTS: Ninety-seven patients with histologically confirmed MFH
      (G1, n=8; G2, n=25; G3, n=64) were analyzed. Local recurrence was 31% after a
      median of 13 months. Distant metastases occurred in 29 patients (30%). After a
      median follow-up of 4.5 years, 54 patients were alive without evidence of
      disease; median survival time was 84 months at a cumulative 5-year survival rate
      of 70%. Tumor size significantly influenced disease-free survival (T2 vs T1,
      P<.01, risk ratio [RR] 6.0), as did tumor depth (subfascial tumors, P<.01, RR
      3.1) and presence of positive lymph nodes (P=.02, RR 6.9). Positive microscopic
      margins and subfascial tumors were associated with an increased local recurrence
      rate (RR 4.8, P<.001 and RR 3.5, P=.02, respectively). Significant multivariate
      risk factors of distant metastases were tumor size, depth, and grade. Though not
      performed in a randomized fashion, a subgroup analysis indicated that adjuvant
      radiation therapy significantly reduced local tumor failure. CONCLUSION: We
      conclude that aggressive, albeit limb-preserving resection of MFH, should be
      performed at initial operation to minimize risk of local recurrence; a strict
      follow-up especially of subfascial tumors should be performed.

PMID- 14694302
TI  - Bleeding during hepatectomy can be reduced by clamping the inferior vena cava
      below the liver.
AB  - BACKGROUND: Control of blood loss is a crucial problem during hepatectomy.
      Bleeding from the inflow system can be controlled by the Pringle maneuver or
      selective vascular occlusion. Bleeding from the outflow system is closely related
      to central venous pressure (CVP). Therefore, in this study, we evaluated whether
      vascular outflow control by clamping the inferior vena cava (IVC) below the liver
      (IVC clamping) during hepatectomy is a safe and effective method to reduce blood
      loss and CVP. METHODS: We reviewed the outcomes of 103 consecutive patients whose
      CVP values were >5 cm H(2)O and who had undergone right or left hemihepatectomy
      between 1995 and 2000. Forty-seven patients who underwent hepatectomy with IVC
      clamping (Group A) between 1998 and 2000 were compared with the previous 56
      patients who underwent hepatectomy without IVC clamping between 1995 and 1997
      (Group B). RESULTS: The CVP decreased by 3.7 cm H(2)0 after IVC clamping.
      Estimated blood loss was 910 mL in Group A and 1177 mL in Group B. (P=.008) No
      severe renal or cardiovascular damage occurred after IVC clamping. CONCLUSIONS:
      IVC clamping is very effective in reducing blood loss during hepatectomy when the
      CVP is elevated and cannot be reduced pharmacologically or by fluid restriction.

PMID- 14694303
TI  - Carotid endarterectomy in high-risk patients: a challenge for endovascular
      procedure protocols.
AB  - BACKGROUND: Many studies have sought to identify certain patient population
      subsets that may be more appropriate for carotid angioplasty and stenting (CAS).
      Current CAS protocols include "high-risk" patients. The goal of this study was to
      compare the perioperative outcome of carotid endarterectomy (CEA) between high
      risk and non-high-risk patients. METHODS: During a 54-month period, 392
      consecutive CEAs were performed in 363 patients (29 bilateral) by a single
      surgeon and entered prospectively into a registry. A high-risk patient subset
      (126, 35%) was defined by the presence of a severe medical comorbidity (ie,
      cardiac dysfunction, pulmonary dysfunction, renal insufficiency) or particular
      anatomic features (ie, contralateral carotid occlusion, ipsilateral carotid
      restenosis after CEA, and "high" carotid bifurcation). Of the 126 CEAs, 96 (76%)
      were performed for symptomatic lesions. Endpoints of the study were perioperative
      stroke, cardiac complication, or death. RESULTS: Overall, there were three
      ischemic strokes (1%) and four cardiac complications (1%). None of the patients
      died. The stroke and cardiac complication rates for the high-risk and non-high
      risk groups were similar (1/126, 1% versus 2/237, 1% and 3/126, 2% versus 1/237,
      1%, respectively), but the cardiac morbidity rate was statistically higher in
      patients with severe medical comorbidity (P=.03), especially in the subset with
      cardiac dysfunction (P=.005). CONCLUSIONS: CEA can be performed in high-risk
      patients with perioperative neurologic and cardiac complication rates comparable
      with those recorded in other patients. The definition of a "high-risk" patient
      should not be considered per se a reason to abandon CEA in favor of CAS.

PMID- 14694304
TI  - Gastric emptying function after ileal J pouch-anal anastomosis for ulcerative
      colitis.
AB  - BACKGROUND: Little is known of the effects on gastric function after ileal J
      pouch-anal anastomosis (IPAA) for ulcerative colitis. This study aimed to
      determine whether patients with postoperative high stool frequency after IPAA
      exhibit impaired gastric function. METHODS: Gastric emptying time (GET) for a
      solid diet (rice gruel) with the use of a radioisotope method and for a liquid
      diet (orange juice) with the use of an acetaminophen method were assessed in 36
      patients with ulcerative colitis more than 30 months after closure of protective
      ileostomy. Patients were divided into 2 groups: 18 patients with stool frequency
      less than 6 per day (group A) and 18 patients with stool frequency more than 7
      per day (group B). GET for solid and liquid diets in groups A and B were compared
      with those in 18 healthy volunteers (group C). We correlated the time of peak
      blood concentration of acetaminophen (TPBCA) and both individual stool frequency
      per day and the length of distal ileum removed. RESULTS: GET for the solid diet
      in groups A and B was not altered by IPAA compared with group C. GET for the
      liquid diet in groups A and B was slower than in group C (P<.0001). GETs for the
      liquid diet at 60 minutes or more in group A were slower than in group B
      (P<.0001); TPBCA was longer in group A than in groups B or C (P<.01). There were
      inverse correlations between TPBCA and individual stool frequency per day and
      between TPBCA and length of distal ileum removed (P<.001). CONCLUSIONS: Rapid
      transit from the stomach of the liquid diet in group B compared with group A may
      influence high stool frequency after IPAA. Our results suggested that, to obtain
      an adequate stool frequency after IPAA, the length of distal ileum removal should
      be less than 15 cm.

PMID- 14694305
TI  - Transmigration across a lung epithelial monolayer delays apoptosis of
      polymorphonuclear leukocytes.
AB  - BACKGROUND: Suppression of polymorphonuclear leukocyte (PMNL) apoptosis may cause
      or exaggerate acute lung injury that is associated with the acute respiratory
      distress syndrome. We hypothesized that transepithelial migration would modulate
      PMNL apoptosis. METHOD: PMNLs that were freshly purified from normal volunteers
      were allowed to migrate across transwell membranes alone or coated with
      monolayers of human lung epithelial cells in response to chemoattractants
      (interleukin-8, formyl-methionylleucylphenylalanine and leukotriene B(4)). We
      assessed for migration efficiency, apoptosis, and functional activity of the
      PMNLs. Changes in the expression of genes modulating PMNL apoptosis were examined
      with messenger RNA and protein analyses. RESULTS: Transepithelial migration
      caused a significant decrease in the percentage of apoptotic PMNLs (interleukin
      8; from 31% to 16% at 8 hours; P<.01). This apoptotic delay was sustained to at
      least 20 hours that was associated with prolongation of PMNL functional activity
      and independent of chemoattractant-type. Gene and protein expression levels of
      the antiapoptotic proteins Mcl-1 and 14-3-3 zeta were either augmented or
      preserved by interleukin-8 treatment alone and after transepithelial migration.
      CONCLUSION: Our data reveal, for the first time, the important role of
      transepithelial migration in the modulation of PMNL apoptosis and may provide
      insights into possible novel targets for the regulation of PMNL apoptosis during
      lung inflammation and injury.

PMID- 14694306
TI  - Ite Boerema--surgeon and engineer with a double-Dutch legacy to medical
      technology.
AB  - Ite Boerema, 1902-1978: a Dutchman with a brilliant academic surgical career, and
      war hero, decorated for resistance to the Germans in World War II. As a man who
      regarded surgery as "engineering in medicine," we still feel his legacy in
      medical technology today, specifically with regard to his work on esophageal
      anastomoses and hyperbaric oxygen therapy. This biography places his major
      contributions to medicine in context of the man himself and of contemporary
      medicine.

PMID- 14694307
TI  - Retrocardiac parathyroid tumor: a rare mediastinal site.

PMID- 14694308
TI  - Training on newly deceased patients.

PMID- 14694309
TI  - Traumatic rectal perforation by an eel.

PMID- 14694310
TI  - Presacral extramedullary hematopoiesis.

PMID- 14694311
TI  - Three unforgettable surgeons.

PMID- 14694320
TI  - Autopsy 101 (CE).
AB  - Although autopsy remains the only definitive way to confirm and sometimes
      diagnose disease, the autopsy rate has continued to decline during the past 3
      decades. Despite numerous publications citing its value, the nursing literature
      lacks information addressing the benefits and implications of the autopsy to
      nurses who provide direct care to older adults. This article provides geriatric
      nurses with information about the benefits, purpose, process, and barriers of
      autopsy to better inform nurses as they ease family concerns and assist
      physicians in obtaining consent for autopsy.

PMID- 14694321
TI  - Evidence-based practice: does it benefit older people and gerontic nursing?
AB  - Evidence-based practice (EBP) has been received with enthusiasm and interest by
      many nurses. It has, however, raised skepticism and negative reactions from
      others. This article seeks to address the place of EBP in care of the elderly by
      outlining EBP and providing some pertinent examples of how it can be used in
      caring for older people. Finally, it promotes EBP as a useful tool, provided its
      definition and implementation are broadened to reflect the science and art of
      nursing.

PMID- 14694322
TI  - Gender differences in religiosity and functional health in the elderly.
AB  - This secondary analysis of a random, community survey of 271 people over 65 years
      old examined gender differences in religious coping, importance of faith, and
      frequency of prayer for their relationship on eight categories of functional
      physical and mental health, as measured by the Medical Outcomes Study Health
      Survey Short-Form 36. Mental health was the only outcome related to the spiritual
      indices for both genders but used differently. Frequency of prayer, a behavioral
      indicator, was positively related to mental health for men. Reliance on religious
      coping and a high importance of one's faith were positively related to mental
      health for women. The results indicated that cognitive coping responses were
      associated with lower anxiety and depression for women, whereas behavioral
      spiritual responses were the relevant variables for male mental health in this
      sample of elders.

PMID- 14694323
TI  - Older adults and NSAIDs: avoiding adverse reactions.
AB  - Monitoring which medications geriatric patients are taking is crucial to their
      health and well-being. Many take over-the-counter nonsteroidal anti-inflammatory
      drugs on a daily basis for common ailments. Even when taken correctly, these
      drugs can harm the elderly because of normal changes that occur as people age.
      Techniques to monitor this population and their use of these medications are
      included to help nurses assist patients avoid adverse reactions and
      complications. This information can be valuable whether you are a nurse working
      in a hospital, office, nursing home, assisted living facility, or any setting
      where care is rendered to the elderly.

PMID- 14694324
TI  - Lack of opioid administration in older hip fracture patients (CE).
AB  - As part of a multisite study funded by the Agency for Healthcare Research and
      Quality, the medical records of older adults with a hip fracture were abstracted
      for acute pain assessment and treatment practices. Of the 709 records reviewed, 8
      patients did not have an opioid administered during the first 72 hours after
      admission to a non-intensive patient care unit. Using a case study approach, this
      article examines demographic characteristics, pain assessment, and analgesic
      administration for these 8 patients to illustrate specific practice problems that
      occur in managing acute pain in older adults. Pain intensity was documented
      infrequently. All 8 patients had a physician order for some type of analgesic,
      and 7 of the 8 had an order for an opioid analgesic. Yet none received an opioid
      during the first 72 hours of care on a general medical-surgical unit, and one
      patient received no analgesia of any kind. The medical records of these hip
      fracture patients indicate that acute pain was underassessed and undertreated.
      Provision of quality pain management will require that nurses address the
      specific practice behaviors identified in the article and correct problems where
      they exist. Key strategies that can be used to improve pain management practices
      include implementation of standardized assessment tools and pain flow-sheets,
      audit and feedback of pain management data with staff, use of pain management
      opinion leaders and change champions, and incorporation of research-based pain
      management practices into performance-evaluation criteria.

PMID- 14694330
TI  - The importance of spiritual assessment: one clinician's journey.

PMID- 14694333
TI  - Gerontologic nurse practitioner care guidelines: hypertension in the elderly
      person.

PMID- 14694334
TI  - Managing chronic pain in the older patient.

PMID- 14694335
TI  - Preventing harm from food-borne illness.

PMID- 14694336
TI  - Safe medication practices: administering medications to elders who have
      difficulty swallowing.

PMID- 14694343
TI  - The epidemiology of the atopic child: who is at risk for what?
AB  - In the past few decades, a number of epidemiologic studies have identified risk
      factors for the development of allergic disease. Although both maternal and
      paternal history of allergy are associated with an increased risk of atopy,
      maternal history of asthma confers the greater risk for childhood asthma, which
      suggests that environmental factors such as the in utero immunologic environment
      may confer additional susceptibility. Cytokine profiles at birth may also
      indicate a predisposition to allergic disease in later childhood. Specifically,
      low interferon-gamma appears to be associated with an increased risk for later
      development of allergic symptoms and atopic disease. Allergen exposure may also
      increase the risk of atopic consequences, but the outcome is highly dependent on
      dose of the allergen, timing of exposure, and, most interestingly, the nature of
      the allergen in question. Endotoxin exposure during infancy has been associated
      with increased wheezing during the first years of life, but several studies
      indicate that early exposure may confer some protection against allergy later in
      life. Clearly, all these factors should be evaluated in identifying the
      appropriate prevention measures and treatment for the child who is at risk for
      allergic disease.

PMID- 14694344
TI  - Systemic effects of local allergic disease.
AB  - Allergic reactions are not confined to the area they originated, but assume a
      secondary systemic, nonanaphylactic element. This element has two consequences:
      it feeds back into the site of the original reaction and it leads to the
      development of distant local manifestations. The well-established interactions
      between the nasal and the lower airways in allergic disease could be viewed as an
      example of this model. Interactions between the nasal mucosa and the paranasal
      sinuses, as well as interactions between the respiratory system, the skin, and
      the gastrointestinal tract have been described and may also fall under the same
      category. Two conduits of the systemic element of allergic disease are proposed:
      the systemic circulation and the nervous system. The mechanisms that lead to the
      development of the systemic element, and particularly the mechanisms of distant
      manifestations after a local allergic reaction have not been elucidated, but they
      probably include intricate interactions between the classic mediators of the
      acute allergic reaction, locally- and systemically-produced cytokines and
      neurotrophins, the vascular epithelium and the adhesion molecule system, the
      chemokine network, antigen-presenting dendritic cells and their interactions with
      T-lymphocytes, as well as a strong bone marrow component. From this perspective,
      the systemic element presents an exciting area of current and future research in
      allergic disease.

PMID- 14694345
TI  - Viral infections, atopy, and asthma: is there a causal relationship?
AB  - Respiratory syncytial virus (RSV) remains the chief cause of hospitalization for
      lower respiratory tract illnesses in both infants and young children, and can
      produce severe outcomes. In addition, several studies have suggested that infants
      in whom RSV bronchiolitis develops may have recurrent wheezing and asthma later
      in childhood. Further complicating the picture is the question of whether there
      is a link between RSV infection in infancy and the development of atopy later in
      childhood. This review will discuss existing data on RSV infection and
      respiratory complications later in life, as well as the link between RSV and
      allergic disease.

PMID- 14694346
TI  - Consider the child: how early should we treat?
AB  - Epidemiologic and natural history studies of asthma have found that, for most
      people who develop asthma, clinical manifestations of the disease occur in the
      early childhood years. Both asthma persistence and severity during early
      childhood predict disease persistence into later childhood and adulthood, at
      which point asthma remission is uncommon. Current pathogenesis paradigms suggest
      that early intervention, before serious pathologic changes occur, may lead to
      optimal outcomes. Early intervention might optimize lung growth and immune
      development, and mitigate asthma persistence and severity. In this overview,
      categories for early intervention strategies for asthma will be based on the
      level of disruption of asthma pathogenesis. "Early interventions" target asthma
      shortly after its onset, "secondary preventions" aim to prevent lung targeting of
      disease processes in the vulnerable host, and "primary preventions" strive to
      promote healthful immune development and lung growth by keeping pro-asthmatic
      immune responses from occurring. This review will discuss recent clinical studies
      that exemplify early intervention and prevention strategies.

PMID- 14694348
TI  - Repeated, intermittent delta(9)-tetrahydrocannabinol administration to rats
      impairs acquisition and performance of a test of visuospatial divided attention.
AB  - The residual neuropsychological effects of marijuana abuse in man indicate a
      dysfunction of the attentional/executive systems. Moreover, experimental
      investigations suggest that repeated, intermittent (subchronic) Delta(9)
      tetrahydrocannabinol (THC), the main psychoactive ingredient of marijuana, alters
      neurotransmission in the frontal cortex of rats and humans, a key neural site
      mediating attention and executive functions. In the present studies, the
      acquisition and performance of a test of visuospatial attention (the lateralized
      reaction time task) after subchronic THC administration (10.0 mg/kg twice daily
      for 14 days) was examined. Rats previously administered THC showed impairments in
      this self-paced version of the classic multiple-choice serial reaction time task,
      which persisted 14 days after the final drug administration. Longer time points
      were not examined. These attentional impairments were transiently reversible with
      an acute amphetamine (0.5 mg/kg) challenge. These behavioral data demonstrate
      that chronic THC administration to rats induces an attentional deficit, similar
      to that observed in humans who abuse marijuana. Finally, amphetamine's ability to
      reverse the attentional impairments provides indirect evidence that monoaminergic
      deficits may be linked to the cognitive dysfunction.

PMID- 14694347
TI  - Sensorimotor gating deficits in transgenic mice expressing a constitutively
      active form of Gs alpha.
AB  - Schizophrenia is a complex disorder characterized by wide-ranging cognitive
      impairments, including deficits in learning as well as sensory gating. The causes
      of schizophrenia are unknown, but alterations in intracellular G-protein
      signaling pathways are among the molecular changes documented in patients with
      schizophrenia. Using the CaMKIIalpha promoter to drive expression in neurons
      within the forebrain, we have developed transgenic mice that express a
      constitutively active form of G(s)alpha (G(s)alpha(*)), the G protein that
      couples receptors such as the D(1) and D(5) dopamine receptors to adenylyl
      cyclase. We have also generated mice in which the CaMKIIalpha promoter drives
      expression of a dominant-negative form of protein kinase A, R(AB). Here, we
      examine startle responses and prepulse inhibition of the startle reflex (PPI) in
      these G(s)alpha(*) and R(AB) transgenic mice. G(s)alpha(*) transgenic mice
      exhibited selective deficits in PPI, without exhibiting alterations in the
      startle response, whereas no deficit in startle or PPI was found in the R(AB)
      transgenic mice. Thus, overstimulation of the cAMP/PKA pathway disrupts PPI, but
      the cAMP/PKA pathway may not be essential for sensorimotor gating. G(s)alpha(*)
      transgenic mice may provide an animal model of certain endophenotypes of
      schizophrenia, because of the similarities between them and patients with
      schizophrenia in G-protein function, hippocampus-dependent learning, and
      sensorimotor gating.

PMID- 14694349
TI  - Anxiolytic activity of the MGLU2/3 receptor agonist LY354740 on the elevated plus
      maze is associated with the suppression of stress-induced c-Fos in the
      hippocampus and increases in c-Fos induction in several other stress-sensitive
      brain regions.
AB  - LY354740 is a potent and selective agonist for group II metabotropic glutamate
      (mGlu) receptors, mGlu2 and mGlu3 receptors, with anxiolytic activity in several
      animal models of anxiety, including the elevated plus maze (EPM) test. Here, we
      studied neuronal activation in mouse brain after EPM exposure in saline- and
      LY354740-treated mice using c-Fos immunoreactivity as a marker. The effect of
      LY354740 on c-Fos expression was also studied in cage control (no EPM) mice.
      Pretreatment with LY354740 (20 mg/kg, s.c.) produced robust anxiolytic behavior
      on the EPM. LY354740 administration decreased EPM-induced increases in c-Fos
      expression in the CA3 of the hippocampus, while having no significant effects on
      basal c-Fos expression in the hippocampus. LY354740 administration significantly
      increased c-Fos expression in specific limbic regions, including the lateral
      division of the central nucleus of the amygdala (CeL), lateral parabrachial
      nucleus, locus coeruleus, and Edinger-Westphal nucleus, whether or not animals
      were exposed to the EPM. Moreover, LY354740 administration per se significantly
      increased c-Fos expression in regions processing sensory information, including
      the paraventricular and lateral geniculate nucleus of the thalamus as well as the
      nucleus of the optic tract and superior colliculus. In particular, the
      suppression of fear-evoked neuronal activity in the hippocampus and drug-induced
      increases in neuronal activation in the CeL have been previously linked to the
      anxiolytic effects of clinically effective drugs such as benzodiazepines, and
      thus may contribute to anxiolytic actions of LY354740 in animal models and human
      anxiety patients.

PMID- 14694350
TI  - Sexual behavior and sex-associated environmental cues activate the mesolimbic
      system in male rats.
AB  - The mesolimbic system plays an important role in the regulation of both
      pathological behaviors such as drug addiction and normal motivated behaviors such
      as sexual behavior. The present study investigated the mechanism by which this
      system is endogenously activated during sexual behavior. Specifically, the
      effects of sexual experience and sex-related environmental cues on the activation
      of several components of the mesolimbic system were studied. The mesolimbic
      system consists of a dopaminergic projection from the ventral tegmental area
      (VTA) to the nucleus accumbens (NAc). Previous studies suggest that these neurons
      are under tonic inhibition by local GABA interneurons, which are in turn
      modulated by mu opioid receptor (MOR) ligands. To test the hypothesis that
      opioids are acting in the VTA during sexual behavior, visualization of MOR
      internalization in VTA was used as a marker for ligand-induced activation of the
      receptor. Significant increases in MOR internalization were observed following
      copulation or exposure to sex-related environmental cues. The next goal was to
      determine if sexual behavior activates dopamine neurons in the VTA, using
      tyrosine hydroxylase as a marker for dopaminergic neurons and Fos
      immunoreactivity as a marker for neuronal activation. Significant increases in
      the percentage of activated dopaminergic neurons were observed following
      copulation or exposure to sex-related environmental cues. In addition, mating and
      sex-related cues activated a large population of nondopaminergic neurons in VTA
      as well as neurons in both the NAc Core and Shell. Taken together, our results
      provide functional neuroanatomical evidence that the mesolimbic system is
      activated by both sexual behavior and exposure to sex-related environmental cues.

PMID- 14694351
TI  - Effects of cocaine self-administration on food-reinforced responding using a
      discrete trial procedure in rats.
AB  - Cocaine addiction has been characterized by a shift from controlled to
      uncontrolled and compulsive drug use. Using novel self-administration procedures,
      we attempted to model this transitional phase and characterize the behavioral
      changes that underlie it. We chose to use food-reinforced responding across the
      light/dark cycle as an indicator of the degree to which cocaine was disrupting
      ongoing behavior as a potential measure of dysregulation. Four groups of rats
      (n=5-6) were given 24-h access to cocaine (1.5 mg/kg/inj) available in 2, 3, 4,
      or 5 discrete trials/h. All rats were given continuous access to a second lever
      that resulted in the delivery of a 45 mg food pellet under a fixed ratio 1
      schedule. The results showed that under low access conditions (eg 2 discrete
      trials/h), both food- and cocaine-reinforced responding were diurnally regulated
      and occurred coincidentally. As access to cocaine was increased, there was a
      progressive disruption in the diurnal control over both food- and cocaine
      maintained responding. High access conditions also produced transient decreases
      in the total levels of food-reinforced responding. These findings suggest that
      high access to cocaine under the discrete trial cocaine self-administration
      procedure produces a transient disruption in the diurnal control over behavior
      maintained by food and that the level of control (or loss of) may be a useful
      marker of dysregulation.

PMID- 14694352
TI  - Interdose elevation in plasma cortisol during chronic treatment with alprazolam
      but not lorazepam in the elderly.
AB  - Benzodiazepines (BZPs) have been shown to reduce hypothalamic-pituitary-adrenal
      (HPA) axis activity acutely in normal humans. In contrast, the effects of chronic
      BZP treatment on the HPA axis have not been well studied, especially in the
      geriatric population. This study examined the acute and chronic effects (3 weeks)
      of alprazolam and lorazepam on plasma cortisol in 68 subjects (60-83 years) who
      received 0.25 or 0.50 mg b.i.d. alprazolam, or 0.50 or 1.0 mg b.i.d. lorazepam,
      or placebo orally according to a randomized, double-blind, placebo-controlled
      parallel design. Memory assessment and blood samples for plasma cortisol were
      obtained prior to the morning dose on days 0, 7, 14, and 21, and at 1, 2.5, and 5
      h postdrug on days 0 and 21. Assessments of anxiety and depression were carried
      out at days 0, 7, 14, and 21 before drug administration. Plasma cortisol was
      affected compared to placebo only by the 0.5 mg alprazolam dose. During the first
      and the last day of treatment, there was a significant drop in cortisol at 2.5 h
      after alprazolam compared to placebo. The predose cortisol levels increased
      significantly during chronic alprazolam treatment, and correlations were found
      between these cortisol changes and changes in depression, anxiety, and memory
      scores. These findings suggest that even a short period of chronic treatment with
      alprazolam, but not lorazepam, may result in interdose HPA axis activation in the
      elderly, consistent with drug withdrawal. If confirmed, this effect may
      contribute to an increased risk for drug escalation and dependence during chronic
      alprazolam treatment.

PMID- 14694353
TI  - Investigation of m1/m4 muscarinic receptors in the anterior cingulate cortex in
      schizophrenia, bipolar disorder, and major depression disorder.
AB  - Abnormal cholinergic neurotransmission has been suggested to occur in psychiatric
      illness. Therefore, this study investigated cholinergic muscarinic receptors in
      the anterior cingulate cortex (ACC) of schizophrenia, bipolar disorder and major
      depression disorder (n=15 per group). We used quantitative autoradiography to
      measure [(3)H]pirenzepine binding to M1 and M4 receptors. Brain tissue was
      obtained from the Stanley Foundation Neuropathology Consortium. [(3)H]pirenzepine
      binding was higher in superficial laminae (I-II) than in deep laminae (III-VI) of
      the ACC. There was a significant 24% reduction in the density of
      [(3)H]pirenzepine in the deep laminae and a significant 19% reduction in the
      upper laminae of the ACC in the schizophrenia group compared to the control
      group. There were no differences in [(3)H]pirenzepine binding in any laminae of
      the ACC in the bipolar or major depression groups compared with the control
      group, except for a trend towards decreased [(3)H]pirenzepine binding in subjects
      with major depression relative to control subjects. We also detected a
      significant effect of suicide on [(3)H]pirenzepine binding in the ACC in subjects
      who died as a result of suicide relative to those who did not, which was more
      evident in patients with schizophrenia. A significant effect of the onset of the
      disease was also observed that was more evident in patients with bipolar
      disorder. The study provides evidence of decreased muscarinic receptor density in
      the ACC in schizophrenia but no evidence for significant changes in these
      receptors in the bipolar and major depression groups. The changes observed in
      schizophrenia may contribute to dysfunctional ACC neural circuits.

PMID- 14694354
TI  - Blockade by the cannabinoid CB1 receptor antagonist, rimonabant (SR141716), of
      the potentiation by quinelorane of food-primed reinstatement of food-seeking
      behavior.
AB  - It has been shown previously that the selective cannabinoid CB1 receptor
      antagonist, rimonabant (SR141716), reduced the intake of palatable food as well
      as the self-administration of several drugs of abuse, suggesting that
      endocannabinoid systems play a role in brain reward function. The present study
      investigated whether a cannabinoid step was involved in food-seeking behavior
      induced by explicit stimuli, using an operant reinstatement procedure in rats.
      Experimental sessions consisted of a 15-min food rewarded period, followed by a
      45-min extinction period. Rimonabant did not affect the response reinstatement
      induced by noncontingent delivery of food pellets, but prevented (0.03-0.3 mg/kg)
      the potentiation by quinelorane, a dopamine D3 receptor-preferring agonist, of
      food-seeking behavior. A possible link between cannabinoid processes and D3-
      and/or D2-mediated dopaminergic transmission was further investigated by studying
      Fos protein expression in cortico-limbic structures in D3 (D3-/-) and D2 (D2-/-)
      knockout mice. Rimonabant (10 mg/kg) increased Fos immunoreactivity in the
      prefrontal cortex (pFCortex) and in the shell but not the core of the nucleus
      accumbens (NAcc). Fos induction by this dose of rimonabant was not seen in mice
      lacking CB1 receptors, providing clear evidence for the involvement of CB1
      receptors. In the NAcc shell, the effect of rimonabant was suppressed in D3-/-,
      but remained unchanged in D2-/- mice. In contrast, Fos expression by rimonabant
      in the pFCortex was impervious to D2 or D3 receptor deletion. In conclusion,
      these data indicate first that rimonabant prevented the enhancement by
      quinelorane of the appetitive value of food pellets unexpectedly delivered during
      extinction and second that rimonabant effects might involve D3 receptor-mediated
      processes. Overall, these results are consistent with the notion that
      endocannabinoid functions control brain reward processes and in particular the
      capacity of explicit stimuli to precipitate food-seeking behavior.

PMID- 14694355
TI  - Practical genetics: alpha-1-antitrypsin deficiency and the serpinopathies.
AB  - Alpha-1-antitrypsin (alpha(1)-antitrypsin) is the archetypal member of the serine
      proteinase inhibitor or serpin superfamily. The most common severe deficiency
      variant is the Z allele, which results in the accumulation of mutant protein
      within hepatocytes. This 'protein overload' causes neonatal hepatitis, cirrhosis
      and hepatocellular carcinoma. The lack of circulating plasma alpha(1)-antitrypsin
      results in early-onset panlobular emphysema. The mechanism underlying the
      deficiency of Z alpha(1)-antitrypsin is due to an aberrant conformational
      transition within the protein and the formation of chains of polymers that tangle
      within the secretory pathway of hepatocytes. This mechanism also underlies the
      plasma deficiency of other members of the serpin superfamily to cause a class of
      diseases called the serpinopathies. Specifically mutant alleles of antithrombin,
      C1-inhibitor and alpha(1)-antichymotrypsin have been reported that favour the
      spontaneous formation of polymers and the retention of protein within
      hepatocytes. The consequent lack of plasma antithrombin, C1-inhibitor and
      alpha(1)-antichymotrypsin results in thrombosis, angio-oedema and emphysema,
      respectively. Moreover, the polymerisation of mutants of neuroserpin results in
      the retention of polymers within neurones to cause the inclusion body dementia,
      familial encephalopathy with neuroserpin inclusion bodies or FENIB. We review
      here the genetic and molecular basis and clinical features of alpha(1)
      antitrypsin deficiency, and show how this provides a platform to understand the
      other serpinopathies.

PMID- 14694357
TI  - Difficulties of genetic counseling and prenatal diagnosis in a consanguineous
      couple segregating for the same translocation (14;15) (q11;q13) and at risk for
      Prader-Willi and Angelman syndromes.
AB  - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are associated with a loss
      of function of imprinted genes in the 15q11-q13 region mostly due to deletions or
      uniparental disomies (UPD). These anomalies usually occur de novo with a very low
      recurrence risk. However, in rare cases, familial translocations are observed,
      giving rise to a high recurrence risk. We report on the difficulties of genetic
      counseling and prenatal diagnosis in a family segregating for a translocation
      (14;15)(q11;q13) where two consanguineous parents carry the same familial
      translocation in this chromosome 15 imprinting region. Both children of the
      couple inherited a chromosomal anomaly leading to PWS. However, a paternal 15q11
      q13 deletion was responsible for PWS in the first child, whereas prenatal
      diagnosis demonstrated that PWS was associated with a maternal 15q11-q13 UPD in
      the fetus. This report demonstrates that both conventional and molecular
      cytogenetic parental analyses have to be performed when a deletion is responsible
      for PWS or AS in order not to overlook a familial translocation and to insure
      reliable diagnosis and genetic counseling.

PMID- 14694358
TI  - Polymorphism R92Q of the tumour necrosis factor receptor 1 gene is associated
      with myocardial infarction and carotid intima-media thickness--the ECTIM, AXA,
      EVA and GENIC Studies.
AB  - The TNFRSF1A gene was screened for polymorphisms in 95 subjects with premature
      myocardial infarction (MI), who also had one parent who had an MI. A total of 10
      polymorphisms were found: three in the promoter region, two in exons and five in
      introns. All polymorphisms were genotyped in ECTIM, a case-control study of MI
      (1815 subjects). The nonsynonymous 92Q allele was found in 1.8, 1.0 and 1.7% of
      controls from Strasbourg, Belfast and Glasgow - respectively; in cases: 4.2, 2.2
      and 3.2%. The population-adjusted odds ratio (OR) for MI associated with allele Q
      carrying was 2.15 (95% CI: 1.09-4.23). To check its possible implication in
      atherosclerosis, this polymorphism was then genotyped in the AXA Study
      (ultrasound examinations of carotid and femoral arteries in the context of an
      employment medical examination, 733 subjects), the EVA Study (ultrasound
      examinations of carotid arteries in a study of cognitive and vascular ageing,
      1092 subjects) and the GENIC Study (on brain infarction (BI), 912 subjects). In
      the AXA Study, among smokers, carrying the 92Q allele was positively associated
      with the presence of a carotid plaque (OR 5.07; 95% CI: 1.64-15.63) and with a
      thickening of the carotid intima-media thickness (IMT) (0.59 (0.11) vs 0.54
      (0.11), P=0.045). In the EVA Study, carriers of allele 92Q had an increased mean
      carotid IMT (0.70 (0.09) vs 0.67 (0.13), P=0.02). No significant association of
      the 92Q allele was found with BI in the GENIC Study. Overall, these results may
      suggest that carriers of the 92Q allele may be at increased risk of
      atherosclerosis.

PMID- 14694359
TI  - mtDNA polymorphisms in five French groups: importance of regional sampling.
AB  - According to classical markers, France has been reported to be regionally
      heterogeneous. Here, we propose to test the homogeneity of the French
      mitochondrial gene pool by analysing D-Loop and coding regions polymorphisms in
      210 individuals stemming from five regions. The data set obtained was also used
      to test the ability of mitochondrial DNA to detect well historically established
      admixtures (admixtures between British/Irish people and native Breton people in
      our case). For these purposes, the sampling procedure was subject to special
      care, concerning the individuals' geographical origin and maternal pedigree. The
      mtDNA analysis revealed some regional specificities in haplogroup distribution,
      which is discussed in terms of successive settlements of France. Statistical
      analyses were conducted to investigate mtDNA diversity and structure within and
      between British, Irish and French groups. They tended to show affinities between
      Morbihan region and Britain plus Ireland. Furthermore, genetic evidences were in
      line with the fact that Morbihan region results from an admixture event, agreeing
      with historical evidences of successive migrations from Britain and Ireland into
      Brittany. These results also tended to outline the fact that two geographically
      very adjacent samples (Morbihan and Finistere), sharing a cultural and linguistic
      area, can present a distinct genetic pattern. Although mtDNA analyses were able
      to identify a historically reported admixture event, we point out here the high
      influence of the sampling procedure and representativeness over the migrations
      hypothesis. We also underline the importance of regional sampling for studies on
      the spread and/or origin of specific European haplogroups (here U5a1a and U8).

PMID- 14694360
TI  - Clinical evidence of the nonpathogenic nature of the M34T variant in the connexin
      26 gene.
AB  - Mutations in GJB2 are the most common cause of congenital nonsyndromic hearing
      loss. The controversial allele variant M34T has been hypothesized to cause
      autosomal dominant or recessive nonsyndromic hearing impairment and some in vitro
      data has been consistent with this hypothesis. In this report, we present the
      clinical and genotypic study of 11 families (seven familial forms of nonsyndromic
      sensorineural hearing loss (NSSNHL) and four sporadic cases) in which the M34T
      GJB2 variant has been identified. The M34T mutation did not segregate with the
      deafness in six of the seven familial forms of NSSNH. Eight persons with normal
      audiogram presented a heterozygous M34T variation and five normal hearing
      individuals were composite heterozygous for M34T and another GJB2 mutation. Four
      normal hearing individuals with a documented audiogram were M34T/35delG and one
      was M34T/(GJB6-D13S1830)del. Screening a French control population of 116
      subjects we have found an M34T allele frequency of 1.72%. This percentage was not
      significatively different from the prevalence of the M34T allele in the deaf
      population, which was 2.12%. All these data suggest that the M34T variant is not
      clinically significant in human and is a frequent polymorphism in France.

PMID- 14694361
TI  - Evidence for segmental bile drainage by hepatic portoenterostomy for biliary
      atresia: Cholangiographic, hepatic venographic, and histologic evaluation of the
      liver taken at liver transplantation.
AB  - BACKGROUND: The result of hepatic portoenterostomy for biliary atresia (BA) has
      improved, but there are some patients who experience worsened liver function in
      the long term after one decrease in jaundice owing to portoenterostomy. However,
      the cause of the liver dysfunction in the long term has not been clearly
      ascertained. METHODS: Five patients (5 to 28 years of age) with BA underwent
      liver transplantation (LT) because of liver dysfunction after successful
      portoenterostomy. To clarify the cause of liver dysfunction occurring in the long
      term, the authors performed a cholangiogram, hepatic venogram, and
      macroscopic/microscopic examination of the liver just after LT. RESULTS: (1)
      Macroscopically, the liver could be divided into 3 areas, the hypertrophic,
      atrophic, and intermediate, with findings between those of the hypertrophic and
      atrophic areas. (2) The divided areas clearly corresponded to the liver segments.
      Segment IV was the hypertrophic area in all patients, but segments VI and VII
      were the atrophic areas in 4 of the 5 patients. (3) Based on the cholangiographic
      and microscopic findings, the hypertrophic area had near-normal structure with
      bile ducts. The atrophic area had severe fibrosis and contained only a few bile
      ducts in the intralobular spaces of liver. CONCLUSIONS: It seems that segmental
      bile drainage must have been established by hepatic portoenterostomy in some
      patients and that some postoperative patients might have worsened liver function
      in the long-term follow-up period accompanied with progression of fibrosis and
      impaired bile drainage. These pathologic changes occur in each liver segment.

PMID- 14694362
TI  - Portoenterostomy for biliary atresia: Long-term survival and prognosis after
      esophageal variceal bleeding.
AB  - BACKGROUND/PURPOSE: Portoenterostomy is the procedure of choice in patients with
      biliary atresia. The authors analyzed the long-term survival rate and
      complications of the procedure in children operated on at The University of Hong
      Kong Medical Centre between 1979 and 2000. METHODS: Seventy-seven consecutive
      patients were analyzed by retrospective chart review. The patients were divided
      into groups according to postoperative bile flow, decade of operation, and age at
      operation. The data were analyzed statistically. RESULTS: The overall actuarial
      transplant-free survival rate was 68% at 10 years after operation. For patients
      with poor, partial, and good postoperative bile flow, transplant-free survival
      rate was 0%, 22%, and 96%, respectively (P <.001). Age and decade of operation
      were not significant risk factors. Esophageal variceal bleeding occurred in 13
      patients and was a prognostic indicator for end-stage liver failure (P =.044);
      the poor prognosis of patients with variceal bleeding, however, was related to
      poor or partial initial bile drainage. CONCLUSIONS: The postoperative serum
      bilirubin level is the most important predictor of long-term survival in patients
      with portoenterostomy for biliary atresia. Esophageal hemorrhage is not an
      absolute indication for urgent liver transplantation in patients with good bile
      drainage.

PMID- 14694363
TI  - Glucocorticoid treatment down-regulates chemokine expression of bacterial
      cholangitis in cholestatic rats.
AB  - BACKGROUND: Postoperative cholangitis is common after operation for biliary
      atresia. Empirical pulse therapy with glucocorticoid is effective in reversing
      some detrimental clinical manifestations, but the rationale for such a therapy
      still is not substantiated. METHODS: Adult male rats were divided into groups
      according to the treatment: sterile normal saline (NS) or Escherichia coli (EC, 1
      mL containing 10(8) cells of ATCC 25922 strain), 1 mL, were infused into the
      proximal choledochostomy (PC) tube 2 weeks after ligation of the PC tube (bile
      duct ligation, BDL), then immediate tube-tube choledocho-choledochostomy (biliary
      drainage, BD) was constructed. A high dose of dexamethasone (DEX, intraperitoneal
      injection; 2 mg/kg of body weight) was given after BD in treatment groups.
      Histopathology of the liver, as well as liver chemokine mRNA expression and serum
      chemokine levels, were studied 24 hours after treatment. RESULTS: Inflammatory
      cell infiltration to the liver was retarded with DEX treatment, which was
      correlated with a significantly lower expression of interleukin-8 (IL-8) and
      monocyte chemoattractant protein-1 (MCP-1) mRNA in the liver (P =.006). Serum IL
      8 and MCP-1 levels were also significantly down-regulated with DEX treatment (P =
      0.008). CONCLUSIONS: Glucocorticoid treatment is effective in modulating IL-8 and
      MCP-1 expression and ameliorating inflammatory cell infiltration in rat liver
      with bacterial cholangitis and cholestasis.

PMID- 14694364
TI  - Percutaneous cholecysto-cholangiography in the diagnosis of obstructive jaundice
      in infants.
AB  - BACKGROUND: Once it is established that a jaundiced infant has an elevated direct
      bilirubin level, the principal diagnostic concern is the differentiation of
      hepatocellular from obstructive cholestasis, of disorders of physiology from
      disorders of anatomy, and of disease that is managed medically from disease that
      is managed surgically. Traditional tests such as ultrasonography, liver biopsy,
      and technotium 99m HIDA scan are often not sufficiently discriminating. General
      anesthesia is required for invasive imaging with endoscopic retrograde cholangio
      pancreatography (ERCP) or operative cholangiogram. The authors describe a facile
      alternative using percutaneous cholecystocholangiography (PCC) with intravenous
      sedation. METHODS: Nine cholestatic infants underwent PCC (age, 27 to 73 days;
      mean, 44 days) after ultrasoundscan, liver biopsy, and (99mTc)HIDA scan failed to
      provide a definitive diagnosis. RESULTS: In the 4 infants without complete
      biliary filling, we found biliary atresia (3) and biliary hypoplasia (1). The
      biliary tree was completely opacified in 5 infants with the following diagnosis:
      neonatal hepatitis (2), duplication of the gallbladder (1), choledochocele (1),
      total parenteral nutrition (TPN) cholestasis (1). There were no complications.
      CONCLUSIONS: When the etiology of cholestasis remains elusive after traditional
      firstline tests, PCC has proven to be an accurate simple alternative in
      differentiating obstructive from hepatocellular causes of infantile cholestatic
      jaundice.

PMID- 14694365
TI  - Slide tracheoplasty for congenital tracheal stenosis.
AB  - BACKGROUND/PURPOSE: The aim of this study was to add to the experience of slide
      tracheoplasty in infants with congenital tracheal stenosis (CTS), to review the
      recent literature on this subject, and to evaluate the diagnostic workup in
      infants with CTS. METHODS: A retrospective review of 3 infants with CTS treated
      with slide tracheoplasty was conducted at our institution. They all underwent
      bronchoscopy, tracheobronchography, and echocardiography. Therapy consisted of
      slide tracheoplasty and simultaneous correction of associated vascular
      malformations. RESULTS: A pulmonary artery sling was missed initially on
      esophagography in 2 patients. Stridor became worse in 2 patients after
      tracheobronchography. After surgical therapy, 2 patients survived and were
      discharged 12 days after surgery. Both are without symptoms at follow-up of 12
      and 20 months. One patient had inoperable restenosis and died 27 days after the
      operation. CONCLUSIONS: Esophagography is not a reliable tool to depict
      associated vascular anomalies for patients with CTS. According to the literature,
      computer tomography has become more reliable to depict the tracheobronchial tree
      and is useful to elucidate associated vascular anomalies as well. Compared with
      other surgical techniques for infants with CTS reported in the literature, slide
      tracheoplasty has fewer postoperative complications and comparable survival
      rates.

PMID- 14694366
TI  - Nitrofen-induced congenital diaphragmatic hernia in rat embryo: what model?
AB  - PURPOSE: The aim of this study was to investigate the natural history of
      congenital diaphragmatic hernia (CDH) in rat embryos with special attention to
      the pathomorphologic changes of diaphragm, liver, intestines, and lungs at
      various stages of embryonic development. METHODS: Pregnant Sprague-Dawley rats
      were given, via a gavage tube, 100 mg nitrofen (Wako Chemicals, Neuss, Germany)
      on day 10.5 of gestation. Fetuses were harvested by laparotomy on day 15.5, 16.5,
      18, and 21. Anatomic study of the diaphragm, herniated viscera, and lungs was
      performed under stereoscope with special attention to the diaphragmatic defect.
      RESULTS: CDH occurred in 44 embryos on right, in 10 on the left, and in 34
      bilateral. In the youngest embryos, the small defect was located in the
      dorsomedial portion of the diaphragm very close to the aortic hiatus. During
      pregnancy, the defect enlarged progressively to occupy more than half of the
      affected hemidiaphragm on day 21. In all animals, regardless of their age and
      side of the defect, the liver was found inside the chest. The intrathoracic mass
      was formed by ingrown hepatic tissue originating from the dorsal surface of the
      intraabdominal liver. It appeared as an accessory liver lobe. The amount of
      intrathoracic liver increased rapidly. From around day 18, the thoracic portion
      of liver, when examined in sagittal plane, was bent forward and assumed an
      uncinate shape. The stomach and small bowel loops were displaced into the chest
      in the oldest examined fetuses. The first sign of reduction of size of the lung
      was seen in 16, 5-day old embryos, and at further stages of embryonic development
      the lung growth impairment strictly paralleled the ingrowth of the liver. The
      natural history of the right and left CDH were very similar. In fetuses with
      bilateral CDH, asymmetry regarding size of the defect and volume of intrathoracic
      hepatic mass was noted with larger defects on the left side in more than 60% of
      animals. CONCLUSIONS: Pathogenesis of nitrofen-induced diaphragmatic defect in
      the rat embryo and CDH in the human fetus seem to differ significantly. Nitrofen
      induces a complex malformation of the embryonic diaphragm and the liver. CDH in
      rat embryo bears more resemblance to a model of space-occupying lesion than to
      human CDH. The induction of localized hepatic proliferation may be a result of
      disturbance of as yet unknown regulatory interaction between hepatic and
      mesenchymal diaphragmatic cells.

PMID- 14694367
TI  - Patterns of cerebral injury in a series of infants with congenital diaphragmatic
      hernia utilizing magnetic resonance imaging.
AB  - BACKGROUND: Congenital diaphragmatic hernia (CDH) is a condition with significant
      mortality and respiratory morbidity. Long-term neurodevelopmental outcome is not
      yet well documented. METHODS: The authors examined all cases of CDH at their
      institution over a 12-month period and performed magnetic resonance imaging (MRI)
      of the brain postoperatively. RESULTS: Eight of 10 patients survived to have an
      MR brain scan. All 8 patients had cerebral injury detected on MRI, with a
      predominance of white matter and deep nuclear gray matter injury. CONCLUSIONS:
      Cerebral injury detected with MRI is common in infants with congenital
      diaphragmatic hernia. The long-term significance of these MRI abnormalities is
      unknown, although the need for good long-term neurodevelopmental follow-up of
      infants with CDH is highlighted.

PMID- 14694368
TI  - Effect of epidermal growth factor on pulmonary hypoplasia in experimental
      diaphragmatic hernia.
AB  - BACKGROUND/PURPOSE: Currently, tracheal occlusion (TO) is a potent stimulus for
      fetal lung growth but also a rather invasive and high-risk procedure. The aim of
      this study was to investigate a new and much less invasive therapeutic strategy,
      namely the maternal intraperitoneal administration of epidermal growth factor
      (EGF) and its effect on pulmonary hypoplasia in the nitrofen-induced congenital
      diaphragmatic hernia (CDH) rat model, especially its effect on type II
      pneumocytes. METHODS: CDH was induced by maternal administration of a single oral
      dose (100 mg) of nitrofen on day 8.5 of pregnancy. Four groups of pregnant rats
      were designed on day 18.5: normal control (n = 4), CDH (n = 4), CDH plus Dex (n =
      4), CDH plus EGF (n = 8). All fetuses were delivered by cesarean section on day
      21. Accordingly, there were 4 groups of fetuses: normal controls (n = 33),
      nitrofen-induced CDH (n = 19), CDH plus Dex treatment (n = 15), and CDH plus EGF
      treatment (n = 24). Lung tissue weight (LW) and body weight (BW) of each fetus
      were recorded, lung histologic and morphometric evaluations were performed, and
      image analysis was combined after lung processing. Transmission electron
      microscopy was used for ultrastructural observation, especially type II
      pneumocytes. RESULTS: CDH was observed in 58 of the 94 rat fetuses (61.7%). Lw/Bw
      of CDH group was significantly lower than those of Dex and EGF (P <.05). The
      lungs of CDH fetuses showed marked hypoplasia, in contrast to improved
      mesenchymal differentiation in that of Dex and EGF fetuses. Statistical
      differences of these morphologic parameters (RAC, MTBD, interstitial%, and
      alveoli%) were found (P <.05). As to ultrastructural features, type II cells of
      CDH lungs had few if any lamellar bodies and cytoplasmic organelles, and showed
      evidence of abundant glycogen granules. The sparse type II cells also showed
      cytoplasmic degenerative changes. By contrast, type II cells of EGF lungs showed
      numerous mitochondria, abundant lamellar bodies (surfactant) and deficiency of
      glycogen granules, and displayed prominent microvillous projections and pitlike
      depressions. The density of type II pneumocyte were 65 +/- 4.5, 31 +/- 3.1, and 8
      +/- 1.5 for EGF, Dex, and CDH, respectively (EGF v Dex, P <.05; EGF v CDH, P <
      0.01). CONCLUSIONS: Compared with TO, prenatal EGF administration as a much less
      invasive therapeutic strategy had shown marked improvement in pulmonary
      hypoplasia and promotion of type II pneumocyte differentiation in the nitrofen
      induced CDH rat model. Thus, EGF could improve the prognosis of CDH by means of
      promoting pulmonary hypoplasia and improving the surfactant deficiency, which
      suggested a potential role in the clinical treatment of CDH.

PMID- 14694369
TI  - Measurement of the ductal L-R shunt during extracorporeal membrane oxygenation in
      the lamb.
AB  - OBJECTIVE: In neonates, initially a ductal shunt is often observed during veno
      arterial extracorporeal membrane oxygenation (ECMO). Depending on the degree of
      pulmonary hypertension in these patients, the ductal shunt will be right to left
      (R-L), left to right (L-R), or bidirectional. A ductal L-R shunt will possibly
      lead to pulmonary hyperperfusion and interact with ECMO weaning. The aim of this
      study was to give more insight in this ductal L-R shunt during ECMO by
      quantification of this shunt in relation to cardiac output and ECMO flow.
      METHODS: In 7 lambs, closure of the duct was prevented by infiltration of the
      ductal wall with 10% formaline. This patent duct could be closed using a
      vesselloop around the duct. Ultrasound flowprobes were installed around the
      pulmonary artery, ascending aorta, and around the ECMO circulation tube. Right
      and left ventricular output and ECMO flow were measured. Ductus flow was defined
      as ductal left to right shunt (Qduct L-R) = flow in ascending aorta (Qao) - flow
      in central pulmonary artery (Qpa) and Qduct R-L = Qpa = Qao. RESULTS: In 6 of 7
      lambs a ductal L-R shunt was observed with a mean shunt of 44% (range, 11 to 79)
      of left ventricular output (Qduct L-R/Qao). Comparison with ECMO flow (Qduct L
      R/Qecmo) showed a mean shunt of 76% (range 15 to 230). When compared with the
      total systemic circulating volume (Qpa + flow in the ECMO circuit [Qecmo]), the
      mean ductal L-R shunt showed a percentage of 51% (range, 7% to 142%).
      CONCLUSIONS: During ECMO, mostly a ductal L-R shunt is observed in this lamb
      model. This ductal shunt is hemodynamically important. The percentages of this
      shunt in comparison with left ventricular output, and total circulating volume
      will support the idea that a ductal L-R shunt during ECMO could be another
      deteriorating factor in the often critical circulation of the neonate on veno
      arterial ECMO.

PMID- 14694370
TI  - Blocking of endogenous nitric oxide increases white blood cell accumulation in
      rat lung.
AB  - BACKGROUND/PURPOSE: Nitric oxide (NO) is a known selective dilator of the
      pulmonary vascular tree. There also is evidence that it plays a role in
      diminishing neutrophil adherence to vascular endothelial cells. An understanding
      of these effects of NO on the pulmonary microcirculation is essential to our
      understanding of its mechanisms of action as well as its potential as a
      therapeutic agent to reduce neutrophil sequestration and subsequent lung injury
      and inflammation from a variety of conditions. This study examines the direct
      effects of inhibition of endogenous NO synthesis with the L-arginine analog,
      Nomega-nitro-L-arginine methyl ester (L-NAME) on neutrophil accumulation within
      the lung. METHODS: Lung samples from 2 groups of rats (n = 14 for each study
      group) were studied. One group was given an intravenous infusion of L-NAME, and
      the other received normal saline (NS), at 2 mg/kg/min for 1 hour. The
      accumulation of neutrophils within the lungs was assessed quantitatively by
      myeloperoxidase (MPO) assay as well as by microscopic examination by a
      pathologist blinded to the 2 groups. RESULTS: The L-NAME group showed increased
      MPO activity in the lung compared with the NS group (mean MPO/mean bicinchoninic
      acid [BCA]: 43.46 +/- 3.10 U/microg v 23.58 +/- 2.48 U/microg; mean MPO/g wet
      lung [gwl]: 57.60 +/- 5.98 U/gwl v 27.10 +/- 3.84 U/gwl, mean +/- SEM; P <.05).
      Histologic examination (n = 6 each group) showed 26 +/- 2 neutrophils/5 hpf for
      the L-NAME group versus 18 +/- 1 neutrophils/5 hpf for the NS group (P < 0.05).
      CONCLUSIONS: These data indicate that the inhibition of endogenous NO has a
      direct effect of increasing neutrophil sequestration in the pulmonary vasculature
      and alveoli. This suggests that endogenous NO plays a critical role in the
      control of neutrophil-endothelial cell interactions in the lung.

PMID- 14694371
TI  - A new technical variant for extramucosal pyloromyotomy: the Tan-Bianchi operation
      moves to the right.
AB  - BACKGROUND: Since its first publication in 1986, the Tan-Bianchi procedure for
      treatment of infantile hypertrophic pyloric stenosis has displayed a growing
      consensus among pediatric surgeons. However, in up to 30% of cases, the
      supraumbilical skin fold incision does not allow a comfortable access. Delivery
      through this route, a large pyloric tumor into the wound to perform a
      pyloromyotomy, can be fairly difficult and time consuming and may damage the
      gastric or duodenal serosa by tearing. Other technical variants have been
      proposed to overcome these limitations, but some are more complicated, some are
      demanding, and some others can worsen the final cosmetic result. METHODS: The
      authors present a personal modification to the Tan-Bianchi procedure that they
      have successfully applied in the last 25 cases of infantile hypertrophic pyloric
      stenosis. A right semicircular umbilical skin fold incision is performed. The
      anterior rectus abdominis muscle (RAM) sheath is incised vertically all around
      the umbilicus, the muscle is laterally displaced, and its posterior sheath and
      the peritoneal cavity entered in the same line. Because all incisions lay in the
      same axis, the abdominal cavity is largely opened by 2 retractors without the
      need for excessive increased traction as it often happens with the supraumbilical
      approach. RESULTS: This technical variant was particularly useful to deliver a
      very large hypertrophic pyloric muscle into the wound. There were no
      complications and excellent cosmetic results were obtained in all patients.
      CONCLUSIONS: These observations suggest that a right semicircular umbilical skin
      fold incision is an attractive alternative for pyloromyotomy mostly when facing
      with a large pyloric tumor.

PMID- 14694372
TI  - Protective effect of polyunsaturated phosphatidylcholine pretreatment on stress
      ulcer formation in rats.
AB  - PURPOSE: The aim of this study was to investigate whether polyunsaturated
      phosphatidylcholine. (PPC) pretreatment has any protective effect on gastric
      mucosal damage induced by cold-restraint stress (CRS) in rats. METHODS: Forty
      swiss albino rats were divided into 3 groups. Group 1 (n = 10) was control, group
      2 (n = 15) was stress ulcer, and group 3 (n = 15) was PPC-treated rats with
      stress ulcer. Stress ulcer was induced by the cold-restraint method for 4 hours
      at 4 degrees C after a starvation period of 72 hours. In the group 3 rats, PPC
      treatment was started 10 days before stress at a dose of 100 mg/d by oral route.
      Rats were terminated, stomachs were excised. Macroscopic ulcer index (UI),
      gastric tissue malondialdehyde (MDA) and superoxide dismutase (SOD) activities,
      plasma total nitrite, and erythrocyte catalase (CAT) concentrations were assayed.
      RESULTS: Histopathologic examination showed a stress ulcer index of 0.12 +/- 0.19
      mm in the treatment group and 23.6 +/- 8.97 mm in the stress ulcer group (P
      <.001). Tissue MDA and SOD concentrations were higher in the stress ulcer group
      than in the treatment group, the differences were statistically significant (P
      <.001). Plasma NO3-+ NO2- levels were higher (P<.005) and CAT levels were lower
      (P <.001) in the nontreatment group. There were no significant differences with
      respect to Ul, MDA, and SOD levels among the control and treatment groups (P
      >.05). CONCLUSIONS: These results suggest that pretreating rats with PPC inhibits
      cold-restraint stress-induced gastric mucosal injury and might be useful in
      preventing stress-induced stomach ulcers.

PMID- 14694373
TI  - Clinical significance of a highly sensitive analysis for gene dosage and the
      expression level of MYCN in neuroblastoma.
AB  - BACKGROUND: The amplification of the MYCN gene is one of the most powerful
      adverse prognosis factors in neuroblastoma, but the clinical significance of an
      enhanced expression of MYCN remains controversial. To reassess the clinical
      implications of MYCN amplification and expression in neuroblastoma, the status of
      amplification and the expression level of the MYCN gene of primary neuroblastoma
      samples were analyzed using highly sensitive analyses. METHODS: Using a
      quantitative polymerase chain reaction (PCR) method (TaqMan), the gene dosages
      (MYCN/p53) of 66 primary neuroblastoma samples were determined. In all 66
      samples, the status of MYCN amplification has been determined previously by the
      Southern blotting method. Of the 54 samples with a single copy of MYCN based on
      the Southern blotting method, 23 samples were analyzed for MYCN amplification
      using the fluorescence in situ hybridization (FISH) method. The expression levels
      (MYCN/GAPDH) of 56 samples were determined by a quantitative reverse
      transcriptase (RT)-PCR method. RESULTS: Of the 54 samples with a single copy of
      MYCN based on the Southern blotting method, 46 samples showed MYCN gene dosages
      of less than 2.0, whereas the remaining 8 samples with dosages of more than 2.0
      were tumors from patients with advanced-stage disease. The results of FISH
      supported the fact that these 8 samples contained a small number of MYCN
      amplified cells. The cases of MYCN gene dosages of more than 2.0 were
      significantly associated with all other unfavorable prognostic factors (an age of
      >1 year at diagnosis [P <.0001], nonmass screening [P =.0003], advanced stage [P
      <.0001], diploid or tetraploid [P <.0001], and a Shimada unfavorable histology [P
      <.0001]). MYCN gene dosages of more than 2.0 were significantly associated with a
      high expression of MYCN (P =.0459). However, the expression level of MYCN was not
      significantly associated with any other prognostic factors. CONCLUSIONS:
      Quantitative PCR may thus be a useful modality for performing a highly sensitive
      and accurate assessment of the amplification and expression levels of the MYCN
      gene. In particular, the combination of the quantitative PCR system and the FISH
      method is considered to be a highly effective method for evaluating the status of
      MYCN amplification. In this highly sensitive analysis, MYCN amplification
      (MYCN/p53 > or = 2.0) was reconfirmed to be a strongly unfavorable factor,
      whereas the expression level of MYCN does not appear to be an independently
      significant prognosis factor.

PMID- 14694374
TI  - Development of an implantable artificial anal sphincter using a shape memory
      alloy.
AB  - BACKGROUND/PURPOSE: The authors created a new artificial anal sphincter using a
      shape memory alloy (AS-SMA) to treat fecal incontinence and evaluated its
      validity. METHODS: AS-SMA consists of 2 Ti-Ni plates to sandwich the intestine
      and generates a pressure of 55 mm Hg at its resting position. With the electric
      power supply, the 2 metals bend to form an almondlike shape making a maximum gap
      of 33 mm between each other at the temperature of 55 degrees C. The device was
      attached to the colostomy in a piglet and was operated several times a day for 1
      month. Fecal continence, bowel movements, and general condition of the piglet
      were recorded. After the experiment, tissue damage around the device was
      investigated. RESULTS: Fecal continence was obtained while the device was in the
      resting position. When it was operated, bowel movements were observed. The bowel
      movements to operations ratio was 82:105 (78%). During the experiment, the animal
      had neither abdominal distension nor vomiting. At the autopsy, there was mild
      inflammation and shallow burns around the device. No compression injury was
      detected. CONCLUSIONS: AS-SMA achieved fecal continence of the colostomy. With
      reduction of the associated side effects, it would be a potential substitute for
      an impaired anal sphincter.

PMID- 14694375
TI  - Is there a role for surgery beyond colonic aganglionosis and anorectal
      malformations in children with intractable constipation?
AB  - PURPOSE: The aim of this study was to assess benefit of surgery in the treatment
      of childhood constipation in children without aganglionosis or anorectal
      malformations. METHODS: Retrospective chart review and follow-up questionnaire of
      19 children (10 girls, age 7.6 +/- 3.9 years) who underwent surgery after colonic
      and anorectal manometry had documented abnormal motility. Children at the time of
      manometric evaluation had symptoms of intractable constipation a mean of 5.1 +/-
      2.5 years. Follow-up questionnaires were administered to caregivers a mean of
      11.4 +/- 9.3 months after surgical intervention. RESULTS: Proximal colonic
      abnormalities were seen in 2 patients, abnormalities involving the distal colon
      and rectosigmoid region in 13 patients, pancolonic abnormalities in 2 patients,
      and incomplete relaxation of the internal anal sphincter in 2 patients. Surgery
      led to increase in frequency of bowel movements per week (8.1 v 1.9; P <.005),
      decrease in soiling episodes per week (2.20 v 4.7; P <.01), and decrease in daily
      use of medications for constipation (0.8 v 2.3; P <.05). Adverse events included
      skin breakdown at site of ostomy (9%), fecal incontinence after pull-through
      procedure (13%), and persistent constipation (4.5%). Parents felt that the
      symptoms after surgery were completely resolved in 89% of patients. CONCLUSIONS:
      Surgery may be beneficial in the management children with chronic intractable
      constipation and documented abnormalities in motility.

PMID- 14694376
TI  - Getting residents in the game: an evaluation of general surgery residents'
      participation in pediatric laparoscopic surgery.
AB  - PURPOSE: In a large children's hospital, the authors evaluated general surgery
      residents' experience with pediatric laparoscopic procedures and the impact of
      their participation on patient outcome. METHODS: The records of all children who
      underwent laparoscopic appendectomy, splenectomy, fundoplication, or
      pyloromyotomy were reviewed. The level of participation by general surgery
      residents in each of these operations was determined. Outcome was assessed for
      these procedures in terms of intraoperative and postoperative complications.
      RESULTS: A resident was the operating surgeon in 164 of 174 laparoscopic
      appendectomies (94%), 37 of 38 laparoscopic splenectomies (97%), 78 of 104
      laparoscopic fundoplications (75%), and 72 of 97 laparoscopic pyloromyotomies
      (74%). Adverse outcomes in the cases in which a resident was surgeon were limited
      to 4 postappendectomy infectious complications, 3 cases of recurrent reflux after
      fundoplication, and one incomplete myotomy and one mucosal injury after
      laparoscopic pyloromyotomy. CONCLUSIONS: The authors have shown that well
      supervised general surgery residents can perform common, pediatric laparoscopic
      operations with excellent results. Although it is essential for established
      pediatric surgeons and fellows in pediatric surgery to acquire expertise in
      minimally invasive surgery, once they have confidence in their own skills they
      may safely permit qualified general surgery residents to perform laparoscopic
      procedures in children.

PMID- 14694377
TI  - Successful in utero gene transfer using a gene gun in midgestational mouse
      fetuses.
AB  - BACKGROUND/PURPOSE: In utero gene therapy offers a number of potential advantages
      over postnatal gene therapy. A latest method of gene transfer to fetuses in utero
      uses a new tool called a gene gun. The gene gun is less invasive and simpler than
      other in utero methods. The current study was designed to determine whether the
      gene gun is an effective tool for transferring genes to mouse fetuses in utero.
      METHODS: Using a gene gun, we transferred plasmids that included enhanced green
      fluorescent protein (EGFP) genes and cytomegalo virus promoters to the abdominal
      skin of 40 A/J fetal mice at each of 3 gestational ages (13, 14, or 15 days).
      Four or 5 days after gene transfer, the number of surviving fetuses was counted,
      and a color image of EGFP in the skin was analyzed for gene transfer rates by
      fluorescence microscopy. Survival rates were analyzed using Fisher's Exact test.
      RESULTS: The mean survival rate was 89.2% (107 of 120) in gene transfer fetuses
      and 91.7% (55 of 60) in controls. There is no difference in survival rate between
      gene transfer fetus and control. The highest gene transfer rate was 100% (37 of
      37) at the gestational age of 14 days. The rate was 97.1% (34 of 35) at
      gestational ages of 13 and 15 days. CONCLUSIONS: The results of this study show
      that in utero gene transfer by gene gun is a less-invasive technique, and the
      gene gun is an effective tool transferring genes to mouse fetuses in utero.

PMID- 14694378
TI  - Associated urologic anomalies in children with solitary kidney.
AB  - PURPOSE: The aim of this study was to investigate the incidence, nature, surgical
      treatment, and outcome of associated urologic anomalies (AUA) in children with
      anatomic or functional solitary kidney (SK). METHODS: In this study, SK was
      defined as the kidney that is present in cases of unilateral renal agenesis (RA),
      or the kidney that is contralateral to a kidney that is nonfunctional secondary
      to either noncystic dysplastic kidney disease (NCDK), or multicystic dysplastic
      kidney disease (MCDK). Fifty-seven consecutive patients with SK (17 owing to RA,
      10 owing to NCDK, 30 owing to MCDK) were reviewed. RESULTS: A total of 23 of 57
      (40%) had AUA in the SK (11 of 17 [65%] of RA cases; 7 of 10 [70%] of NCDK cases;
      and 5 of 30 [17%] of MCDK cases). The incidence of AUA in MCDK was significantly
      lower than that in RA or NCDK (p <.01: Mann-Whitney U test). Surgery was
      performed on 20 of 23 (87%) for vesicoureteric reflux (VUR) in 13, pelviureteric
      junction stenosis in 3, and ureterovesical junction stenosis in 4. Surgery was
      not performed in 3 of 16 with VUR because the VUR that was present was of low
      grade. AUA-related symptoms such as urinary tract infection and abdominal mass
      were seen in 15 of 23; the remaining 8 were asymptomatic. Mean age at surgery was
      4.8 years. There were no operative or postoperative complications, and all cases
      are well without impaired renal function or hypertension after a mean follow-up
      period of 5.3 years. CONCLUSIONS: In patients with SK, 40% had AUA in the renal
      collecting system of the SK. All children with SK should undergo a screening
      voiding cystourethrography (VCUG) even in the absence of hydronephrosis or UTI,
      and early recognition and treatment are imperative to decrease the long-term risk
      for renal damage.

PMID- 14694379
TI  - Laparoscopic decapsulation of congenital splenic cysts: a step forward in splenic
      preservation.
AB  - PURPOSE: The aim of this study was to evaluate the role of laparoscopic
      decapsulation in the management of congenital splenic cysts in children. METHODS:
      Patients who presented over the last decade with congenital splenic cysts and
      were treated with laparoscopic decapsulation were reviewed retrospectively. The
      authors performed 4 procedures in 3 patients aged 10, 11 (and later 13), and 13
      years. In all cases there was progressive enlargement of a single cyst, which lay
      in the upper pole of the spleen in 3 instances and in the lower pole in the
      fourth. Pneumoperitoneum was induced using the Veress needle technique, and 3 or
      4 ports were utilized. Cysts were aspirated initially before marsupialization
      with excision of around two thirds of the cyst wall. Both endoshears and the
      harmonic scalpel were used with good hemostatic effect. RESULTS: All patients had
      a good outcome with cyst resolution on long-term follow-up using serial
      ultrasound scanning. The first patient (in 1993) remained 3 days as an in patient
      postoperatively, and the others stayed overnight only. One patient had a new cyst
      near the first 30 months after the initial procedure. This again was dealt with
      laparoscopically, with patient discharge the following day. There were no
      complications in the short or long term. Histology in all cases confirmed a
      simple epithelial cyst. Median follow-up was 2 years (range, 6 months to 8
      years). CONCLUSIONS: Our experience shows that laparoscopic decapsulation is an
      effective means of managing congenital splenic cysts and that both harmonic
      scalpel and endoshears are satisfactory dissecting instruments. Extensive
      marsupialization is probably unnecessary in these larger cysts, because long-term
      follow-up has shown no increased risk of recurrence after leaving a significant
      proportion of the cyst wall behind. This approach helps avoid major surgery in
      these cases.

PMID- 14694380
TI  - The effect of zinc aspartate pretreatment on ischemia-reperfusion injury and
      early changes of blood and tissue antioxidant enzyme activities after unilateral
      testicular torsion-detorsion.
AB  - BACKGROUND/PURPOSE: The aim of this study is to investigate the effect of zinc
      aspartate (ZA) pretreatment on ischemia-reperfusion (I/R) injury and blood and
      tissue antioxidant enzyme activity early after unilateral testicular torsion
      detorsion (T/D). METHODS: Forty prepubertal male Sprague-Dawley rats (weight 160
      to 220 g) were divided into 4 groups each containing 10 rats. Surgery was
      conducted under intraperitoneal 1-shot ketamine (50 mg/kg) anesthesia. The
      scrotum was entered through a midline incision. Rotating the left testis 720
      degrees in a clockwise direction was the model of the testicular torsion. Group 1
      was for the basal values. Group 2 had 4 hours T/D. Group 3 also had 4 hours T/D
      and pretreated with 50 mg/kg intraperitoneal ZA injection half an hour before
      detorsion. Group 4 was designed as a sham group. In the Group 2 and Group 3, the
      tunica vaginalis was opened, and left testicles were rotated clockwise 720
      degrees and maintained in this torsion position by fixing with a silk suture to
      the scrotal wall. The scrotum was closed and 4 hours later reentered for
      testicular detorsion. After spermatic cord detorsion, the scrotum was closed. At
      the end of 4 hours detorsion period, bilateral orchiectomies were performed, and
      5-mL intracardiac blood samples were taken. Blood and tissue superoxide dismutase
      (SOD), catalase (CAT) activities, and malondialdehyde (MDA) levels were measured,
      and histopathologic examination was performed. RESULTS: Group 2 and group 3 had
      decreased blood SOD and CAT activities and elevated MDA levels indicating I/R
      injury. The 2 groups were also different from each other for these parameters
      reflecting the beneficial effect of ZA pretreatment (P <.05). The decreased
      ipsilateral tissue SOD and CAT activities in group 2 were different from the
      other groups including group 3 (P <.05). Ipsilateral tissue MDA levels of both
      group 2 and group 3 were elevated. Group 2 had higher values than group 3 (P
      <.05). In addition, specimens from group 2 had a significantly greater histologic
      injury than group 3 (P <.05). These findings were also supporting the beneficial
      effect of ZA pretreatment. All measurements of contralateral tests were similar
      to the basal values for all groups (P >.05). CONCLUSIONS: ZA pretreatment reduces
      I/R injury by its antioxidant effects after unilateral testicular T/D and affects
      the antioxidant enzyme systems.

PMID- 14694381
TI  - Pancreatic trauma in children.
AB  - BACKGROUND/PURPOSE: The aim of this study was to determine the etiology,
      associated injuries, and outcome of children with pancreatic injuries. METHODS: A
      retrospective review was conducted of children under 16 years with pancreatic
      trauma admitted to the Children's Hospital at Westmead (CHW) from January 1983 to
      September 2002. Deaths were reported to the New South Wales Paediatric Trauma
      Death Registry (State Registry) from January 1988 to September 2002. RESULTS:
      Sixty-five cases were identified: 46 patients were admitted to CHW, and 22 deaths
      were reported to the State Registry (including 3 deaths at CHW). The median age
      was 6 years (range, 1 to 14 years). Boys accounted for 60% (n = 40) of cases,
      decreasing to 50% (n = 11) of those that died. Motor vehicle injuries (MVI) were
      the most common mechanism, accounting for 40% of survivors and 77% of those who
      died. Children were restrained incorrectly in 48% of all cases and in 67% of
      those who died. Significantly more children who died had head, chest, and
      abdominal visceral injuries, compared with those who survived. Death occurred as
      a result of head injuries in 68%, with only 3 deaths directly attributed to
      pancreatico-duodenal injuries. CONCLUSIONS: Pancreatic injuries remain uncommon
      in children. The most frequent mechanism was MVI, with incorrect use of passenger
      restraints an important contributing factor. Whereas mortality was mainly caused
      by other injuries, 3 deaths were directly attributable to pancreato-duodenal
      trauma.

PMID- 14694382
TI  - Diagnosis of a proximal tracheoesophageal fistula using three-dimensional CT
      scan: a case report.
AB  - Missed proximal tracheoesophageal fistulas (TEF) after repair of an esophageal
      atresia (EA) with distal TEF are rare. The diagnosis usually is made on the basis
      of bronchoscopy and esophagoscopy, which can be inaccurate. Recent advances in
      computerized tomography (CT) have allowed saggital, coronal, and 3-dimensional
      reconstruction of any structure or organ. The authors report a case in which 3
      dimensional CT was used to assist in the diagnosis of a missed proximal TEF in a
      16-year-old girl.

PMID- 14694383
TI  - An infant with systemic hypertension, renal artery stenosis, and neuroblastoma.
AB  - A newborn girl with neuroblastoma presented with hypertension (blood pressure
      200/140 mm Hg). The concentration of active renin in the ipsilateral renal vein
      was exceedingly high compared with those in the other venous systems, and
      angiography results showed narrowing of the contralateral 2 renal arteries. The
      tumor regressed in size after chemotherapy, but the blood pressure remained high.
      Percutaneous transluminal angioplasty (PTA) for the left renal arteries was
      performed twice, the first one at 5 months of age, which achieved some success in
      the recovery of impaired kidney function. At 8 months of age, she underwent
      radical resection of the neuroblastoma and removal of the right kidney, and the
      blood pressure promptly returned to normal postoperatively. The current patient
      represents the second youngest, well-documented case of renovascular hypertension
      with neuroblastoma in early infancy.

PMID- 14694384
TI  - Combined pentalogy of Cantrell with tetralogy of Fallot, gallbladder agenesis,
      and polysplenia: a case report.
AB  - A male newborn with pentalogy of Cantrell, tetralogy of Fallot, agenesis of the
      gallbladder, and polysplenia died at 3 days of age. Polysplenia was not
      previously reported in this association.

PMID- 14694385
TI  - Waugh's syndrome: report of two cases.
AB  - The association of intussusception and intestinal malrotation has been reported
      rarely in the literature. This association is called Waugh's syndrome. The
      authors report 2 cases of Waugh's syndrome and discuss diagnostic features and
      treatment methods.

PMID- 14694386
TI  - Paramesocolic hernias: consequences of delayed diagnosis. Report of three new
      cases.
AB  - BACKGROUND: If internal hernias account for less than 1% of the causes of
      intestinal obstruction, the paraduodenal or paramesocolic hernias (PMH) represent
      50% of the 500 published as of the year 2000. Despite their congenital character,
      they are diagnosed more frequently in adulthood, with a mean age of 38 years at
      diagnosis. In the last few years, diagnoses are being made earlier. With the goal
      of increased early diagnosis and decreased mortality associated with these
      internal hernias, the authors report on 3 young patients with PMH. METHODS: Three
      cases of paramesocolic hernias are reported, 2 right (RPMH) and 1 left (LPMH).
      They all had a history of symptoms of recurrent abdominal pain of variable
      frequency and intensity but of sufficient importance to justify previous
      diagnostic studies. The 2 patients with RPMH, a 3-year-old boy and a 17-year-old
      woman, presented symptoms of intestinal obstruction and had necrosis of the small
      intestine leading to short-bowel syndrome. The LPMH patient, a 13-year-old boy,
      suffered recurrent abdominal pain from the age of 3. Gastroesophageal reflux was
      diagnosed, and surgery was performed at the age of 4 years. A laparoscopy at 13
      years of age found no pathology. A new upper gastrointestinal tract series found
      retroperitoneal and paraduodenal jejunum incarceration, partially obstructing the
      duodenum. During surgery, the adhered jejunal section was restored
      intraperitoneally, and the open Treitz arch was closed. The authors have not
      found the anatomic characteristics of this case in the literature. CONCLUSIONS:
      Delays and errors in PMH diagnosis may result in irreparable damage. Differential
      diagnosis workups of patients with recurrent abdominal pain syndrome should
      always include PMH.

PMID- 14694387
TI  - False aneurysm of the palmar arch in a child.
AB  - False aneurysm of the arteries of the hand are extremely rare in children,
      despite high frequency of hand injuries. The authors report one case of false
      aneurysm in the superficial palmar arch in a 5-year-old girl. The aneurysm was
      resected, and vascular reconstruction was performed by end-to-end microscopic
      anastomosis. Discussion about preoperative explorations, therapeutic options, and
      a current review of the literature are proposed.

PMID- 14694388
TI  - Sentinel lymph node biopsy in juvenile secretory carcinoma.
AB  - A 9-year-old girl presented with a 3-year history of a right breast mass.
      Excisional biopsy showed a secretory carcinoma. A treatment plan of simple
      mastectomy and axillary sentinel lymph node biopsy was chosen. She remains free
      of disease at 3-year follow-up. Sentinel lymph node biopsy offers an approach to
      stage the axillary lymphatic basin with a lower complication rate than formal
      dissection. The authors advocate its use in the treatment of pediatric breast
      cancer.

PMID- 14694389
TI  - Torsion of an indirect hernia sac causing acute scrotum.
AB  - A 6-year-old boy presented with an acute scrotum and was found at surgical
      exploration to have torsion and infarction of an indirect hernia sac. This
      represents the sixth reported case of this entity in the literature. The
      pediatric surgical specialist and those in the acute care setting should be aware
      of this consideration in the differential diagnosis of the acute scrotum.

PMID- 14694390
TI  - Transient antiphospholipid syndrome in an infant with segmental small bowel
      infarction.
AB  - The clinical picture of venous or arterial thrombosis in the presence of
      circulating antiphospholipid antibodies is referred to as the antiphospholipid
      syndrome. A 5-month-old baby girl who was quite healthy so far was referred to
      our clinic with irritability, vomiting, and abdominal distension for 30 hours.
      Surgical exploration exposed a gangrenous ileal segment about 15 cm long. The
      postoperative period was unremarkable. Investigation to identify the risk factors
      for mesenteric thrombosis found anticardiolipin antibodies (isotype Ig G) and
      decreased protein C level. Protein S and antithrombin III were within normal
      levels. Hb electrophoresis results showed no HbS, and neither Factor V Leiden nor
      prothrombin 20210 mutations were detected. Eight months postoperatively,
      anticardiolipin antibodies were found within normal levels. Lupus anticoagulant,
      ds DNA, and ss DNA were negative. Direct coombs test and protein C, C3, and C4
      were also within normal levels. She had no thrombotic episode in the 24 months
      postoperatively, although no anticoagulant medication was administered. To the
      authors' knowledge this case is the first report of segmental intestinal
      infarction in transient antiphospholipid syndrome in the pediatric population.

PMID- 14694391
TI  - The giant umbilical cord: an unusual presentation of a patent urachus.
AB  - Umbilical cord anomalies remain a frequent newborn nursery consultation for the
      pediatric surgeon. The authors report on a giant umbilical cord associated with a
      patent urachus. Although it is an uncommon anomaly, operative exploration must be
      carried out to repair the associated urachal remnant.

PMID- 14694392
TI  - Balloon-occluded retrograde transvenous obliteration performed in a pediatric
      patient with isolated gastric fundal varices.
AB  - BACKGROUND: For giant gastric varices in association with portal hypertension,
      endoscopic treatment often is difficult. Although balloon-occluded retrograde
      transvenous obliteration (B-RTO) has been performed successfully in adult
      cirrhotic patients, there has been no report in pediatric patients. METHODS: A 10
      year-old girl with biliary atresia (BA) who had been free of jaundice after
      hepatic portoenterostomy was detected to have isolated gastric fundal varices by
      routine endoscopy. They gradually enlarged up to 4 cm in diameter, showing a
      tense appearance, so prophylactic treatment was conducted. Magnetic resonance
      angiography showed the blood flow of the varices mainly drained by a large
      gastrorenal shunt. A balloon catheter was introduced into the gastrorenal shunt
      via the femoral vein and was inflated to occlude the outflow of the varices. Five
      percent ethanolamine oleate was injected into the varices, and the outflow
      occlusion was kept for more than 30 minutes. Extensive thrombosis was achieved by
      an additional embolotherapy after 17 months. Throughout the course, the patient
      has been doing well without bleeding or worsening of the liver function tests.
      CONCLUSIONS: B-RTO for isolated gastric fundal varices has been performed safely
      in a pediatric patient and seems effective in reducing the variceal size and
      tension.

PMID- 14694393
TI  - Dieulafoy lesion in a one-year-old child.
AB  - The Dieulafoy lesion is a rare cause of severe upper gastrointestinal bleeding
      associated with a significant mortality. Rebleeding from undiscovered lesions is
      frequent and often fatal. The outcome depends on a high degree of suspicion for
      the condition. In any age group, the entity may be underdiagnosed rather than
      truly rare. It is particularly uncommon in infants. The authors report the case
      of the youngest patient so far to suffer from a Dieulafoy lesion.

PMID- 14694394
TI  - Hooking a chronically embedded esophageal coin.
AB  - A penny chronically embedded within the wall of the esophagus was removed using a
      laparoscopic cautery hook when conventional foreign body forceps were
      ineffectual.

PMID- 14694396
TI  - Patent ductus venosus in children: a case report and review of the literature.
AB  - A 10-year-old girl with a patent ductus venosus associated with multiple
      autoimmune disorders presented with hypoxia, cyanosis of her lips, and exertional
      dyspnea. Ultrasonography and abdominal computed tomography of the liver showed a
      communication between the portal vein and the inferior vena cava through a patent
      ductus venosus. Portography showed flow from the portal vein directly into the
      inferior vena cava via the portosystemic shunt. The portosystemic venous shunt
      ratio was estimated to be 71.8% by scintigraphy using 123I-IMP. Intraoperatively,
      the authors diagnosed this portosystemic shunt as patent ductus venosus because
      of the absence of the ductus venosus on real anatomic position. The portal venous
      pressure was 8.2 cm H2O, which increased to 17.7 cm H2O when the ductus venosus
      was temporarily occluded. After surgical ligation of the ductus venosus, the
      color of liver improved, indicating restored liver circulation. The postoperative
      course was uneventful, and the patient has been asymptomatic for 6 months.

PMID- 14694397
TI  - Hepatobiliary mucinous cystadenoma in a child.
AB  - The authors present a 4-year-old boy who had a large mucin-hypersecreting
      hepatobiliary cystadenoma. The tumor caused a hepato-colo-cutaneous fistula,
      which produced a large amount of external fluid loss. Total excision and the
      repair of the fistula could be possible after shrinkage of the tumor with the use
      of selective embolization of the feeding artery by interventional radiology.

PMID- 14694398
TI  - Undifferentiated embryonal sarcoma in children: beware of the solitary liver
      cyst.
AB  - Undifferentiated embryonal sarcoma (UES) of liver is a rare form of liver tumor
      in children. It may have an atypical presentation leading to delay in diagnosis.
      The authors report on 3 consecutive children with this condition, each of them
      presenting in older children who presented with this condition and an initial
      diagnostic dilemma. One of them presented initially with a solitary cyst, the
      second with severe abdominal pain, and the third with intermittent fever.
      Preoperative chemotherapy was successful in shrinking the tumors in 2 children to
      allow anatomic liver resection with tumor-free margin. Both remain free of
      recurrence 2 years after completing treatment.

PMID- 14694399
TI  - Is a modified central bisegmentectomy a volume-saving operation for pediatric
      hepatoblastoma?
AB  - The authors report on an 11-month-old girl who presented with a hepatoblastoma.
      The tumor was located in Couinaud's segments IV, V, VII, and VIII. She received
      adjuvant chemotherapy in accordance with the Japanese Study Group for Pediatric
      Liver Tumor Protocol-2, and the tumor thereafter showed a partial response,
      involving segments IV and VIII. She thereafter underwent a modified central
      bisegmentectomy (segments IV, VIII, and a part of V). The postoperative course
      was uneventful, and the patient is now doing well 22 months after the operation.
      The authors consider the central bisegmentectomy to be a volume-saving operation,
      and, based on a volumetric analysis, the estimated preserved volume of the
      functioning liver parenchyma was determined to be 87%. However, if using a right
      trisegmentectomy, the preserved volume was estimated to only be 44%. The authors
      consider a central bisegmentectomy to be a useful alternative operation for
      patients with centrally located hepatoblastoma to minimize both morbidity and
      mortality.

PMID- 14694400
TI  - Laparoscopic cholecystecomy in a 16-day-old infant with chronic cholelithiasis.
AB  - A 16-day-old girl with demonstrated evidence of cholelithiasis was treated
      initially conservatively on the assumption that the gallstone would resolve
      spontaneously. However, when repeat ultrasound scan showed a large gallstone and
      intrahepatic ductal dilatation indicative of antenatal common duct obstruction,
      the infant underwent laparoscopic cholecystectomy with an intraoperative
      cholangiogram. The patient did well postoperatively and was on regular feeding by
      postoperative day 1. An intraoperative cholangiogram showed an impacted stone in
      the infidibulum of the gallbladder. Gross and histopathologic findings indicated
      chronic cholecystitis. Based on an extensive review of the literature, this case
      appears to be the first reported incidence of chronic cholecystitis in a neonate
      and that of the youngest patient to undergo a laparoscopic cholecystectomy with
      intraoperative cholangiogram.

PMID- 14694401
TI  - Extrahepatic biliary atresia and caudal regression syndrome in an infant of a
      diabetic mother.
AB  - Although most cases of extrahepatic biliary atresia are thought to result from
      perinatal obliterating inflammation, some are associated with a faulty
      morphogenesis. The authors report on a baby girl of a mother with ill-managed
      insulin-dependent diabetes mellitus. The baby presented with sacro-coccygeal
      agenesis, clubfoot, and ano-urinary incontinence. In addition, there was
      polysplenia, no inferior vena cava, and the portal vein was grossly distorted.
      Progressive conjugated hyperbilirubinemia prompted liver biopsy at 4 weeks of
      age, showing intracanalicular cholestasis without fibrosis. The diagnosis of
      extrahepatic biliary atresia was confirmed during laparotomy performed for
      hepatoportojejunostomy. Some cases of extrahepatic biliary atresia might be part
      of a spectrum of malformations associated with maternal diabetes mellitus.

PMID- 14694402
TI  - Idiopathic spontaneous pneumomediastinum: an uncommon emergency in children.
AB  - Spontaneous pneumomediastinum (SPM) occurs rarely in children. The diagnosis is
      based on physical examination and chest radiography. Conservative therapy usually
      leads to recovery. However, SPM in association with severe hypoxia, tachycardia,
      metabolic acidosis, and high ventilation pressures indicates clinically
      significant tension in the mediastinum. A collar mediastinotomy is the treatment
      of choice in these circumstances.

PMID- 14694403
TI  - A case of laryngeal atresia (congenital high airway obstruction syndrome) with
      chromosome 5p deletion syndrome rescued by ex utero intrapartum treatment.
AB  - The authors report a case of laryngeal atresia (congenital high airway
      obstruction syndrome [CHAOS]) that was diagnosed prenatally. The patient
      underwent successfully tracheostomy by ex utero intrapartum treatment (EXIT). The
      fetal ultrasonography and magnetic resonance imaging MRI showed a typical CHAOS
      pattern with expanded hyperechogenic lungs, inverted diaphragms, and a dilated
      trachea. Recently, 3 cases of prenatally diagnosed CHAOS were reported to be
      treated successfully by EXIT. The clinical manifestation and course of this case
      was not similar to these 3 cases. The 3 previous patients did not fare as well
      during gestation and were delivered earlier than that in our case. In our case,
      fetal hydrops was seen at 23 gestational weeks, but it gradually subsided and
      disappeared at 30 gestational weeks. The fetus was stable and well. After
      delivery at 39 weeks, the baby received respiratory assistance by ventilator
      assistance. After 3 days, she could breath well on her own. The patient also had
      chromosome 5p deletion syndrome and perineal groove. More experience in treating
      CHAOS cases with EXIT to fully estimate its clinical course and prognosis is
      needed.

PMID- 14694404
TI  - Foveolar hyperplasia secondary to cow's milk protein hypersensitivity presenting
      with clinical features of pyloric stenosis.
AB  - Pyloric stenosis is one of several causes of infantile nonbilious vomiting. A 7
      week-old boy presenting with symptoms suggestive of this was found to have a
      prepyloric lobular mass causing near-complete gastric outlet obstruction. The
      histology showed localized hypertrophic gastropathy with hyperplasia and
      tortuosity of foveolar cells reminiscent of Menetrier changes. Postsurgical
      excision, the child continued vomiting until removal of bovine and soy proteins
      from his diet. The clinical presentation, pathology, and response to restrictive
      diet suggested cow's milk protein allergy as key. The literature describing
      infantile focal foveolar hyperplasia and Menetrier disease is reviewed, stressing
      the rarity of allergy as cause.

PMID- 14694405
TI  - A case of acrocephalosyndactyly with low imperforate anus.
AB  - The authors report a case of a female acrocephalosyndactyly with imperforate anus
      without fistula, which is rare in girls. Acrocephalosyndactyly is characterized
      by premature closure of the sutures (craniosynostosis) and fusion or webbing of
      hands and feet (syndactyly). The most general types of the syndrome are the Apert
      syndrome and the Pfeiffer syndrome. They usually have some fibroblast growth
      factor receptor (FGFR) gene mutations, so that acrocephalosyndactyly is thought
      to be involved in "FGFR-related craniosynostosis." To the authors' knowledge,
      only 4 cases of anorectal anomaly in acrocephalosyndactyly have been reported in
      the world. The relationship between anorectal anomaly and the FGFR gene is not
      clear now, but might be clarified in the future.

PMID- 14694406
TI  - Methemoglobinemia and hemolysis after enteral administration of methylene blue in
      a preterm infant: relevance for pediatric surgeons.
AB  - A preterm infant had methaemoglobulinemia and hemolytic anemia after enteral
      administration of methylene blue. The dye was administered to exclude a
      tracheoesophageal fistula. Methylene blue is a noxious product, especially in
      neonates. It should be considered a potential cause of acquired
      methemoglobulinemia, even after enteral administration.

PMID- 14694407
TI  - Ureteral triplication: the first report in China.
AB  - Ureteral triplication is a rare congenital anomaly of the urinary tract. Since
      the first description of ureteral triplication by Wrany in 1870, only about 100
      cases have been reported in the literature. Pediatric cases are very few. Here, 2
      cases of ureteral triplication were reported. Diagnosis was established
      preoperatively in 1 case and intraoperatively in 1. To the authors knowledge,
      this is the first report of ureteral triplication in China.

PMID- 14694419
TI  - Determination of ampicillin and amoxycillin by flow injection chemiluminescence
      method based on their enhancing effects on the luminol-periodate reaction.
AB  - In this work, a new flow injection chemiluminescence method is described for the
      determination of ampicillin and amoxycillin. The method is based on the strong
      enhancing effects of these antibiotics on the luminol-periodate reaction. The
      present method allows the measurements of ampicillin in the range 0.02-1.0 mg/L
      range and amoxycillin in the range 0.1-10.0 mg/L range with the relative standard
      deviations within 0.8-2.0%. The sampling frequency was calculated about 90/h. The
      method was successfully applied to the determination of ampicillin and
      amoxycillin in pharmaceutical preparations. A brief discussion on the possible
      chemiluminescence reaction mechanism is presented.

PMID- 14694420
TI  - A novel chemiluminescent method for determination of phloroglucinol.
AB  - It was found that the inhibition and enhancement by phloroglucinol of the
      chemiluminescence from the luminol-K3Fe(CN)6 system were dependent on the pH of
      luminol solution and the concentration of phloroglucinol. In Na2CO(3)-NaHCO3
      buffer, phloroglucinol exhibited strong chemiluminescent enhancement at pH 9.4.
      On this basis, a flow injection method was developed for the determination of
      phloroglucinol. The method was simple, rapid, convenient and sensitive, with a
      detection limit of 2.0 x 10(-9) mol/L. It is effective for determining
      phloroglucinol in the range of 1.0 x 10(-5)-5.0 x 10(-9) mol/L. The relative
      standard deviation is 1.3% within one day and 3.2% between days for the
      determination of 5.0 x 10(-7) mol/L phloroglucinol. The method has been
      successfully used to determine phloroglucinol in environmental water, with
      satisfactory results.

PMID- 14694421
TI  - A competitive marathon race decreases neutrophil functions in athletes.
AB  - A full marathon is the longest running race in official track events and is a
      form of acute exercise. However, no studies have examined the acute neutrophil
      function response to a competitive marathon race. Thirty-six male athletes who
      had just completed the 42.195 km course of the 50th Beppu-Oita Mainichi Marathon
      were enrolled in this study. Neutrophil oxidative burst activity, phagocytic
      activity and expression of CD11b and CD16 per cell were measured by flow
      cytometry immediately before and after the marathon. Total leukocyte/neutrophil
      counts increased significantly (p < 0.001), whereas total oxidative burst
      activity per neutrophil cell decreased significantly after the race (p < 0.001).
      Furthermore, total phagocytic activity per neutrophil cell also decreased after
      the race, although it was not significant (p = 0.08). Although CD11b expression
      per cell did not change, the expression of CD16 per cell significantly decreased
      (p < 0.001) after the race. In conclusion, a competitive marathon race decreased
      neutrophil functions (oxidative burst activity and phagocytic activity), which
      may be partly due to a decrease in CD16 expression. The increase in total
      neutrophil counts might reflect a compensatory response to counteract the
      decrease in neutrophil functions.

PMID- 14694422
TI  - Ecabet sodium attenuates reactive oxygen species produced by neutrophils after
      priming with bacterial lipopolysaccharides.
AB  - The pathogenic roles of reactive oxygen species (ROS) have been implicated in
      ulcerative colitis (UC). The aim of this study was to examine the effects of
      ecabet sodium on ROS produced by human neutrophils, particularly after being
      primed by bacterial lipopolysaccharides (LPS). Neutrophils were isolated from six
      healthy volunteers. Each well of a 96-well microplate received neutrophil
      suspension (1.0 x 10(5) cells) and the plates were incubated at 37 degrees C for
      30 min with or without E. coli LPS (f.c. 0.001 ng/ micro L). Ecabet sodium (f.c.
      0-5.0 mg/mL) was added before starting or after finishing the incubation.
      Neutrophils were stimulated by opsonized zymosan (OZ; 1.0 mg/mL) or calcium
      ionophore (A21837; 0.3 micro mol/L) and luminol-dependent chemiluminescence
      response was measured using a Lumi Box H-1000. Ecabet sodium attenuated ROS
      production at a concentration of 5.0 mg/mL (p < 0.05) in LPS-primed neutrophils.
      However, attenuating effects were not significantly different when ecabet sodium
      was added before or after the incubation with E. coli LPS. Ecabet sodium may have
      some attenuating effects on ROS produced by human neutrophils even after
      neutrophils are primed by bacterial LPS. These results may explain, in part, the
      therapeutic effects of ecabet sodium for UC.

PMID- 14694423
TI  - Comparison of oxidative stress induced by ciprofloxacin and pyoverdin in bacteria
      and in leukocytes to evaluate toxicity.
AB  - Oxidative stress induced by ciprofloxacin and pyoverdin, a leukotoxic pigment,
      was studied by comparing their effect in bacteria and leukocytes.
      Chemiluminescence (CL) assays with lucigenin or luminol were adapted to measure
      the stimuli of superoxide anion (O2 -) and other reactive species of oxygen (ROS)
      in bacteria. Ciprofloxacin principally induced the production of O2 - in the
      three species studied: Staphylococcus aureus, Enterococcus faecalis and
      Escherichia coli. Lucigenin CL assay showed high oxidative stress in S. aureus
      due to its low superoxide dismutase (SOD) activity, whereas E. coli exhibited
      important SOD activity, responsible for little production of O2 - in absence or
      presence of ciprofloxacin. Reduction of nitroblue of tetrazolium (NBT) was
      applied. This assay indicated that there was higher oxidative stress in S. aureus
      and E. faecalis than in E. coli. The comparison of oxidative stress generated in
      bacteria and leukocytes was used to check the selective toxicity of ciprofloxacin
      in comparison with pyoverdin. Ciprofloxacin did not generate significant stimuli
      of O2 - in neutrophils, while pyoverdin duplicated the production of O2 -. CL and
      NBT were useful to study the leukotoxicity of ciprofloxacin. Oxidative stress
      caused by the antibiotic and the leukotoxic pigment was similar in bacteria.

PMID- 14694424
TI  - Chemiluminescence behaviour of alkaline earth metal ions in the potassium
      permanganate-fluorescein reaction.
AB  - A chemiluminescence (CL) signal was observed when alkaline earth metal ion
      solution, Mg2+ or Ca2+ or Ba2+, was injected into a reaction mixture of
      fluorescein and potassium permanganate. A possible CL mechanism is proposed based
      upon the CL, fluorescence and UV-visible spectra. Furthermore, the feasibility of
      the application of these reactions to the analysis of these alkaline earth metal
      ions was evaluated and the analytical parameters of the methods were determined.

PMID- 14694425
TI  - Spatial and temporal distribution of a bioluminescent-marked Pseudomonas putida
      on soybean root.
AB  - The ability of rhizobacteria to compete with other microorganisms for root
      colonization may be critical for its establishment on a root. Over a 6 day
      period, visualization of the spatial and temporal rhizosphere distribution of a
      bioluminescent-marked rhizobacterium, Pseudomonas putida, strain GR7.4lux, was
      examined on soybean grown in non-sterile soil conditions. Luminometry
      technologies showed a rapid root distribution of rhizobacteria where
      bioluminescence was particularly intense on the seed and upper root parts. The
      results provide new information on rhizobial root distribution, where, using
      enrichment broth, 50% of the root tips were still colonized by rhizobacteria up
      to 6 days after sowing. This suggests that rhizobial enrichment is required to
      detect low populations at the root tip. Bioluminescent technology represents a
      promising alternative to previous methods for studying rhizobial growth and
      distribution on roots.

PMID- 14694426
TI  - Luminescence literature. Time-resolved fluorescence 2000-2002.

PMID- 14694427
TI  - Messenger RNA stockpile of cyclin B, insulin-like growth factor I, insulin-like
      growth factor II, insulin-like growth factor receptor Ib, and p53 in the rainbow
      trout oocyte in relation with developmental competence.
AB  - In the present study, correlations between the oocyte messenger RNA (mRNA)
      stockpile of Cyclin B, insulin-like growth factor I (IGF-I), insulin-like growth
      factor (IGF-II), insulin-like growth factor receptor Ib (IGFR Ib), and p53
      transcripts and the developmental competence of the oocyte were studied. For this
      purpose, post-ovulatory ageing was used as a tool to generate oocytes of varying
      developmental competence. Mature female rainbow trout were held at 12 degrees C
      and periodically checked for ovulation. Oocytes were collected from each female
      at ovulation and 5, 14, 21 days later. For each collected egg batch, the
      abundance of several mRNAs in the oocyte was analyzed by real-time PCR and embryo
      development was monitored after fertilization. Egg quality was estimated not only
      through embryonic survival but also by studying the occurrence of specific
      morphological abnormalities. The present study showed that oocyte post-ovulatory
      ageing was associated with variations of the relative abundance of several
      studied transcripts within the oocyte. In addition, the abundance of specific
      mRNAs could be correlated with either the embryonic survival or the occurrence of
      malformations. Thus, the abundance of IGFR Ib and Cyclin B transcripts in the
      oocyte was correlated with the occurrence of morphological abnormalities observed
      at yolk-sac resorption (negatively for IGFR Ib and positively for Cyclin B),
      while the maternal stockpile of IGF-I, IGF-II, and IGFR Ib mRNAs was positively
      correlated with embryonic survival.

PMID- 14694428
TI  - Analysis of differential maternal mRNA expression in developmentally competent
      and incompetent bovine two-cell embryos.
AB  - The main objective of this study was to identify mRNA transcripts associated with
      embryonic developmental competence. In cattle, mRNA transcripts, ribosomes, and
      proteins accumulated during the growth phase are drawn on to sustain maturation,
      fertilization, and the initial cell cycle divisions up to the 8- to 16-cell
      stage. Early cleaving mammalian zygotes are more likely to develop to the
      blastocyst stage than their later cleaving counterparts, thus reflecting the
      intrinsic quality of the oocytes from which they originated. We describe the
      combination of this well-established model for the retrospective determination of
      developmental competence in mammalian oocytes with a technique for wide screening
      of differential gene expression in different biological populations. Immature
      cumulus oocyte complexes were recovered from surface visible follicles on
      abattoir ovaries, washed, and submitted to routine in vitro maturation and
      fertilization. Two-cell embryos were removed from culture at 3-hr intervals from
      24 to 42 hr post insemination (pi). Two populations of two-cell embryos were
      identified; those that cleaved early (before 27 hpi) and those that cleaved late
      (after 33 hpi). Suppressive subtractive hybridization was carried out on cDNA
      from the two populations, following which, differentially expressed amplicons
      were subcloned and sequenced. The sequences were submitted to the nonredundant
      and expressed sequence tag (EST) databases at NCBI using the BLAST algorithm. The
      differential expression of three selected candidate genes that were identified as
      putatively upregulated in the early cleaving zygotes were chosen for further
      investigations; histone H3, cyclin B1, and GDF-9B. Using quantitative real time
      PCR we have shown that histone H3A is significantly more abundant in embryos that
      cleave earliest.

PMID- 14694429
TI  - Transition from embryonic to adult transcription pattern of serotonin N
      acetyltransferase gene in avian pineal gland.
AB  - The study reports the change of transcription pattern of serotonin N
      acetyltransferase gene and melatonin receptor genes during ontogenesis of the
      avian pineal gland. The RT-PCR technique was used to investigate the expression
      of the arylalkylamine N-acetyltransferase (AA-NAT) and melatonin receptor genes
      during development of the pineal glands isolated from Japanese quail (Coturnix
      coturnix japonica) embryos incubated from 3 days on until hatching (17 days), and
      in some organs (pineal, brain hemisphere, eye, leg, heart) of the 3-day-old quail
      embryo. It was shown that two phases of AA-NAT expression are observed during
      pineal gland development. The first, embryonic-type phase, lasts from the
      beginning until 7-10 days of incubation, and is marked by the presence of two RT
      PCR products for AA-NAT: the shorter mature form without intron (238 bp), and the
      longer form (323 bp) containing an unprocessed intron of 85 bp. The second, adult
      type phase is characterized by the presence of a single mature transcript,
      containing no intron; it starts from 7 to 10 days of incubation and lasts until
      hatching and in the adult pineal. The duration of this transition time from the
      embryonic to the adult transcription pattern in the quail pineal gland from 7 to
      10 days of incubation we attribute to asynchronic embryo development, because
      quail chicks usually hatch between the 16th and 19th day of incubation. Analysis
      of the AA-NAT protein sequences for chick and quail (GeneBank accession no. U 46
      502 and AF 007 068, respectively) revealed their perfect homology with the part
      of protein read from the sequence present in the adult-type phase of the pineal
      gland (the RT-PCR product of 238 bp). The presence of the intron (in the 323 bp
      RT-PCR product, accession no. AY 197 460) in the embryonic-phase of the pineal
      gland changes the reading frame of the mRNA sequence and the hypothetical
      resulting protein loses its homology with the chick and quail AA-NAT enzyme
      starting with 105th amino acid of the complete chick AA-NAT protein comprising
      205 amino acids (accession no. U 46 502). In the whole embryos at stages 1-8
      (according to the Hamburger-Hamilton classification) both RT-PCR products with
      and without intron were consistently found, and individual tissues from 3-day-old
      embryos also produced two AA-NAT products, i.e., the expression was of the
      embryonic-type. At the time of transition from the embryonic to the adult AA-NAT
      transcription pattern, in 7-11-day-old embryos, all three melatonin receptor
      transcripts (mel-1a, mel-1b, and mel-1c) were observed in the pineals, without
      consistent modifications of the band intensity. In the adult pineal, a single
      mature AA-NAT transcript was present as well as all three melatonin receptor
      transcripts, usually with preferential expression of the mel-1a band. The
      transition time from the embryonic to adult AA-NAT expression pattern coincides
      well with the acquisition of functional activity and the appearance of melatonin
      synthesis in the embryonic pineal reported for chicken, as related to quail. We
      suggest that the change in transcription pattern of the AA-NAT gene may reflect
      another, still unknown mechanism of regulating AA-NAT activity during
      ontogenesis, at the level of mRNA processing, whose specificity (or not) for
      embryonic development we wish to establish in the future.

PMID- 14694430
TI  - Endophyte-infected tall fescue diet alters gene expression in heifer luteal
      tissue as revealed by interspecies microarray analysis.
AB  - Cattle consuming endophyte-infected tall fescue grass have an associated
      reduction in circulating progesterone and reduced reproductive rates. In this
      study, commercially available rat microarrays were used to analyze the gene
      expression in luteal tissues from heifers fed endophyte-free fescue, endophyte
      infected fescue, or endophyte-infected fescue supplemented with the dopamine (DA)
      antagonist, domperidone. The number of hybridized spots represented approximately
      40% of the total 10,000 rat genes/ESTs evaluated. Each luteal sample was analyzed
      in triplicate, resulting in within treatment correlation coefficients of >/=0.98.
      Median values of mRNA abundance from luteal tissue taken from the endophyte
      infected fed heifers revealed 598 genes and ESTs that were down regulated and 56
      genes and ESTs that were upregulated compared with luteal mRNA values from the
      endophyte-free treatment. There were fewer comparative differences between median
      values from luteal mRNA from the endophyte-free versus feeding endophyte-infected
      plus domperidone treated heifers. Only 19 genes and ESTs were upregulated and two
      were down-regulated.

PMID- 14694431
TI  - Expression and localization of fibroblast growth factor (FGF) family members
      during the final growth of bovine ovarian follicles.
AB  - The aim of this study was to investigate the possible participation of fibroblast
      growth factor (FGF) family members: FGF1, FGF2, and FGF7, and their receptor
      variants: FGFR, FGFR2IIIb, and FGFR2IIIc in theca interna (TI) and granulosa cell
      (GC) compartments of bovine follicles during final growth. A classification of
      follicles into five groups (<0.5; >0.5-5; >5-20; >20-180; >180 ng/ml,
      respectively) was performed according to the follicular fluid (FF) oestradiol
      17beta (E) content. The mRNA expression and protein localization was analyzed by
      reverse transcription-polymerase chain reaction (RT-PCR) and
      immunohistochemistry. FGF1 mRNA expression was relatively high in TI and lower in
      GC, and without any regulatory change for both tissue compartments during final
      follicular growth. The FGF1 protein could be predominantly localized in the
      cytoplasm of GC, in smooth muscle cells of blood vessels, in the rete ovarii, and
      at a lesser degree in theca cells. FGF2 mRNA in TI increased significantly in
      large follicles and was low and without any regulatory change in GC. FGF7 mRNA
      expression was relatively high in TI and very low in GC. For FGF7 in mature
      follicles a marked staining of the TI and the basal layers of the GC could be
      demonstrated. The mRNA signal for the FGFR in TI increased significantly with
      beginning of E production (E > 0.5-5 ng/ml FF) and was without any regulatory
      change in GC. The mRNA expression of FGFR2IIIb was relatively high in GC and
      increased significantly during final growth of follicles in contrast to the TI
      with very low expression. The FGFR2IIIc mRNA expression in TI and GC was
      relatively high but without any clear change. Our results suggest that FGF growth
      factor family members are involved in process of folliculogenesis and especially
      during final growth of the preovulatory (dominant) follicle by stimulation of
      angiogenesis and GC survival and proliferation.

PMID- 14694432
TI  - Expression of heat shock protein in broiler embryo tissues after acute cold or
      heat stress.
AB  - This study evaluated the expression of heat shock protein 70 kD (hsp70) in
      broiler chicken embryos subjected to cold (Experiment I) or high incubation
      temperature (Experiment II). In each experiment, fertile eggs were distributed in
      three incubators kept at 37.8 degrees C. At day 13 (D13), D16, and D19 of
      incubation, the embryos were subjected to acute cold (32 degrees C) or heat (40
      degrees C) for 4-6 hr. Immediately after cold or heat exposure, samples from the
      liver, heart, breast muscle, brain, and lungs of 40 embryos were taken per age
      and treatment (control or stressed embryos). A tissue pool from 10 embryos was
      used as 1 replication. The levels of hsp70 in each tissue sample was quantified
      by Western blot analysis. The data were analyzed in a 3 x 2 factorial arrangement
      of treatments with four replications. hsp70 was detected in all embryo tissues,
      and the brain contained 2- to 5-times more hsp70 protein compared to the other
      tissues in either cold or heat stressed embryos. hsp70 increases were observed in
      the heart and breast muscle of cold stressed embryos at D16 and D19,
      respectively. Heat stressed embryos showed an increase of hsp70 in the heart at
      D13 and D19, and in the lung at D19 of incubation. Younger embryos had higher
      hsp70 synthesis than older embryos, irrespective of the type of thermal stressor.
      The results indicate that the expression of hsp70 in broiler chicken embryos is
      affected by cold and heat distress, and is tissue- and age-dependent.

PMID- 14694433
TI  - Activity of an enzyme converting single-chain tissue-type plasminogen activator
      to the two-chain form in preovulatory human follicular fluid.
AB  - The biological role of the tissue-type plasminogen activator (tPA)/plasmin system
      has long been implicated in ovarian function. We have recently shown that the
      follicular fluid of human ovaries contains an alpha(2)-macroglobulin/protease
      complex capable of converting single-chain (sc) tPA to the two-chain (tc) enzyme
      tPA, suggesting the occurrence of its corresponding enzyme in a free form in the
      fluid. The aim of the current study is therefore to gain further information
      about the putative sctPA-converting enzyme present in follicular fluid.
      Incubation of human recombinant sctPA with the fluid brought about the production
      of tctPA. It was also demonstrated that tctPA production resulted in the
      activation of endogenous fluid plasminogen. Production of tctPA and plasmin both
      was strongly inhibited by aprotinin, suggesting that the enzyme is a serine
      protease. The sctPA-converting enzyme was partially purified from the fluid by
      column chromatographies. The enzyme preferably hydrolyzed synthetic peptide
      substrates containing arginine at the P(1) position. The enzyme preparation had a
      protease inhibitor profile similar to that observed with the crude fluid sample.
      These results clearly demonstrated that follicular fluid contains an enzyme
      capable of efficiently converting sctPA to tctPA. Discovery of this sctPA
      converting enzyme strongly suggests that the tPA/plasmin system in the
      preovulatory follicle of human ovaries is operated through the proteolytic
      conversion of sctPA to tctPA rather than being regulated by a fibrin-dependent
      mechanism.

PMID- 14694434
TI  - Vitrification of pronuclear-stage mouse embryos on solid surface (SSV) versus in
      cryotube: comparison of the effect of equilibration time and different sugars in
      the vitrification solution.
AB  - The cryopreservation of pronuclear-stage embryos has particular importance in
      transgenic technology and human assisted reproductive technology (ART). The
      objective of this study was to improve the efficiency of cryopreservation of
      pronuclear-stage mouse embryos. Two vitrification methods (solid surface
      vitrification (SSV) vs. vitrification in cryotube) have been compared with
      special emphasis on the effect of the exposure of the embryos to the solutions
      for various times and the sugar content (trehalose, sucrose, or raffinose) of the
      vitrification solutions. Pronuclear-stage embryos were either exposed to 1 M
      dimethyl sulfoxide (DMSO) + 1 M propylene-glycol (PG) solution for 2, 5, 10, or
      15 min or not exposed to this "equilibration" solution. The vitrification
      solutions consisted of 2.75 M DMSO and 2.75 M PG in M2 medium supplemented with 1
      M trehalose (DPT), 1 M sucrose (DPS), or 1 M raffinose (DPR). In the cryotube
      method, groups of 15-25 embryos were transferred into a 1.8 ml cryotube
      containing 30 microl of DPT, DPS, or DPR. After 30 sec, the cryotubes were
      directly plunged into liquid nitrogen (LN(2)) and stored for 1 day to 1 month.
      Vitrified samples were warmed by immersing the cryotubes in a 40 degrees C water
      bath and then immediately diluted with 300 microl of 0.3 M trehalose, sucrose, or
      raffinose in M2. In the SSV method, after equilibration 15-20 embryos were
      exposed to DPT, DPS, or DPR solutions for around 20 sec before being dropped in 2
      microl drops onto a pre-cooled (-150 to -180 degrees C) metal surface. Vitrified
      droplets were stored in cryovials in LN(2). Warming was performed by transferring
      the vitrified droplets into 0.3 M solutions of trehalose, sucrose, or raffinose
      at 37 degrees C, respectively. Results showed that both SSV and cryotube
      vitrification methods can result in high rates of in vitro blastocyst development
      (up to 58.3 and 68.5% with DPR, respectively), not statistically different from
      that of the controls (58.3 and 64.4%). Even without the equilibration step prior
      to vitrification, relatively high-survival rates have been achieved, except for
      the DPS solution. In conclusion, vitrification of pronuclear-stage mouse embryos
      can result in high rates of in vitro development to blastocyst, and the use of
      raffinose in the vitrification solution is advantageous to improve cryosurvival.

PMID- 14694435
TI  - Sexual dimorphism in interferon-tau production by in vivo-derived bovine embryos.
AB  - Interferon-tau (IFN-tau) is an anti-luteolytic factor responsible for preventing
      regression of the maternal corpus luteum (CL) during early pregnancy of cattle.
      In vitro-produced (IVP) bovine embryos first produce IFN-tau as blastocysts. In
      the present study, we have examined whether sexually dimorphic production of IFN
      tau, which is observed among IVP blastocysts, also occurs among in vivo-produced
      blastocysts, and whether this difference between the sexes persists to day 14
      when silencing of one of the X-chromosomes in the trophectoderm is complete.
      Embryos were flushed from cattle that had been superovulated and bred by AI.
      Blastocysts (63 male, 62 female) recovered between days 8.5 and 9.5 of pregnancy,
      were cultured individually. No differences were observed between males and
      females in either their developmental stage or quality at the beginning, during,
      and at the end of culture. Female embryos produced more IFN-tau than males by 24
      hr (mean values, males: 16.6 +/- 3.7, females: 49.4 +/- 9.0 pg per embryo; P <
      0.05) and 48 hr (male: 189.8 +/- 37.1, female: 410.9 +/- 66.6 pg per embryo; P <
      0.05). However, the variability in IFN-tau production between individual
      blastocysts was so great that IFN-tau secretion is unlikely to be of value as a
      non-invasive means to predict embryo sex. When conceptuses were recovered at day
      14, elongating males (n = 25) and females (n = 24) were similar in dimension and
      did not differ in their IFN-tau production after 4.5 hr (male: 2,550 +/- 607,
      female: 2,376 +/- 772 ng per conceptus) and 24 hr (male: 12,056 +/- 2,438,
      female: 8,447 +/- 1,630 ng per conceptus) of culture. Thus, sexual dimorphism in
      IFN-tau production is observed in both IVP and in vivo-produced expanded
      blastocysts, but is lost by day 14 of in vivo development.

PMID- 14694436
TI  - Improved embryo development with decreased apoptosis in blastomeres after the
      treatment of cloned bovine embryos with beta-mercaptoethanol and hemoglobin.
AB  - In preliminary experiments, the treatment of donor somatic cells with beta
      mercaptoethanol (ME) or hemoglobin (Hb) improved in vitro-development of bovine
      cloned embryos. This study was subsequently evaluated whether the exposure to Hb
      and/or ME during in vitro-maturation or embryo culture could further promote the
      development of embryos cloned with ME-treated donor cells. A prospective,
      randomized study was conducted and, embryo development, cell number, and
      apoptosis in blastocysts were monitored. A significant (P < 0.05) effect was
      found after the combined treatment of cloned embryos with Hb (1 microg/ml) and ME
      (10 microM); the development of morulae (53 vs. 35%) was greatly improved, which
      resulted in enhanced blastocyst formation (38%). However, cell number and
      apoptosis in blastocysts were predominantly affected by ME rather than Hb; a
      significant increase in total cell number of blastomeres (142-154 vs. 123
      cells/embryo), inner cell mass (ICM) (39-41 vs. 27), and trophectoderm (TE) (103
      114 vs. 98), and the ratio of ICM to TE cell number (0.26-0.27 vs. 0.22) was
      found. Also, the apoptosis index indicating the ratio of apoptotic cell to normal
      blastomere number was greatly reduced after ME treatments (0.85 vs. 0.056-0.069).
      When embryos cloned with ME-treated cells were cultured in Hb + ME-containing
      medium, any of the treatments to recipient oocytes before enucleation did not
      further promote the development. In conclusion, combined treatment of cloned
      embryos with Hb + ME not only improved in vitro-development but also decreased
      blastomere apoptosis. The use of ME-treated donor cells and the culture of cloned
      embryos in Hb + ME-containing medium yielded the optimal results for promoting
      the production of blastocysts with improved quality.

PMID- 14694437
TI  - Mitochondrial DNA heteroplasmy in calves cloned by using adult somatic cell.
AB  - Adult somatic cell cloned calves were produced by somatic cell nuclear transfer
      prepared by fusion of cultured ear fibroblast from a Holstein cow into enucleated
      oocytes of Luxi Yellow cow. In order to determinate the source of mitochondrial
      DNA of cloned calves, we designed the breed-specific PCR primers by aligning the
      known D-loop sequences of Bos taurus and analyzed the displacement loop sequences
      of five live cloned calves by breed-specific primers PCR. The results
      demonstrated that mtDNA originated from Holstein breed and that from Luxi breed
      co-exist in all five live calves.

PMID- 14694438
TI  - Embryonic development of in vitro matured and in vitro fertilized dog oocytes.
AB  - In several studies, early cleavage stage canine embryos have been derived from in
      vitro fertilized oocytes cultured under various conditions. Despite these
      results, IVF protocols for canine oocytes have yielded low fertilization rates.
      In this study, Experiment I compared the effects of tissue culture medium (TCM)
      199 supplemented with either (A) 1 microg/ml estradiol or (B) 20 microg/ml
      estradiol + 1 microg/ml human somatotropin (hST) on the in vitro nuclear
      maturation rate of canine oocytes. Meiotic progression to the metaphase I and II
      (MI/MII) stages at 72 hr of in vitro culture (IVC) was 10.2% (11/108) in medium A
      versus 14.1% (30/142) in medium B (P = 0.802). In Experiment II, cleavage rate
      was determined among oocytes recovered from ovaries of bitches at different
      reproductive stages. Oocytes (n = 888) were retrieved from bitches at the
      follicular, anestrous, and luteal stages and selected for high morphological
      quality. Oocytes were matured for 48 hr in TCM-199 supplemented with 1 microg/ml
      hST + 20 microg/ml estradiol. Oocytes were in vitro fertilized with fresh canine
      spermatozoa that had been isolated on a Percoll gradient, and were cultured in
      synthetic oviduct fluid (SOF) medium with bovine serum albumin (BSA; 4 mg/ml) up
      to 5 days in 5% CO(2) in air at 37 degrees C. A proportion of oocytes (30.6%)
      with identifiable nuclear material had cytoplasm penetrated or fertilized by
      sperm. The percentage of oocytes developing into early stage embryos was 10.1%
      (27/267). Although pronuclear development was observed to be higher for oocytes
      recovered at the follicular phase, the cleavage rate was similar among oocytes
      recovered from bitches at the follicular, anestrus, and luteal stages. There was
      no correlation between the proportion of capacitated or acrosome reacted
      spermatozoa and pronuclei formation and/or percent cleavage. It was concluded
      that TCM-199 supplemented with 1 microg/ml hST and estradiol (20 microg/ml)
      supports nuclear and cytoplasmic maturation of canine oocytes. In this study,
      meiotic competence was verified by the in vitro production (IVP) and development
      of embryos up to the 8 cell-stage. Furthermore, the results indicate that, under
      the described conditions and despite the influence of reproductive status of the
      bitch on the developmental competence of in vitro fertilized oocytes to the
      pronuclei stage, cleavage was independent of donor's reproductive estrous cycle
      stage.

PMID- 14694439
TI  - Inhibition of bovine sperm-oocyte fusion by the p-aminophenyl derivative of D
      mannose.
AB  - Several steps in the process of mammalian fertilization are mediated by
      carbohydrates. This study investigated the role of the p-aminophenyl derivative
      of d-mannose (APMP) during bovine fertilization. Inseminating cumulus-oocyte
      complexes (COCs) in the presence of increasing APMP concentrations resulted in a
      significant dose-dependent decrease of the fertilization rate (P < 0.05). No
      negative effect of 50 mM APMP on total sperm motility and progressive motility
      was found. Subsequently, the fertilization steps at which this blocking effect
      could be exerted were investigated, i.e., sperm penetration of the cumulus
      oophorus, sperm-zona binding, acrosome reaction, sperm-oolemma binding, and/or
      sperm-oocyte fusion. Inseminating cumulus-enclosed and cumulus-denuded oocytes in
      the presence of 50 mM APMP significantly decreased the fertilization rate to a
      comparable minimum level (P < 0.05). There was no significant relationship
      between the number of spermatozoa bound to the zona pellucida and the APMP
      concentration, and APMP nor d-mannosylated bovine serum albumin (BSA) suppressed
      or stimulated sperm acrosomal status. Inseminating zona-free oocytes in the
      presence of 50 mM APMP did not influence sperm-oolemma binding, but significantly
      inhibited sperm-oocyte fusion (P < 0.05). Preincubating zona-free oocytes with
      200 microg/ml Con A but not with 50 mM APMP inhibited the sperm-oocyte fusion
      rate to the same extent as when the gametes were simultaneously exposed to 50 mM
      APMP. These data indicate that the blocking effect of APMP on bovine
      fertilization is mainly due to an inhibition of sperm-oocyte fusion, probably by
      specific obstruction of the sperm receptor sites that are responsible for the
      fusion process.

PMID- 14694440
TI  - Oocyte maturation in Xenopus laevis is blocked by the hormonal herbicide, 2,4
      dichlorophenoxy acetic acid.
AB  - Oocyte maturation is dependent on a complex program of morphological,
      ultrastructural, and biochemical signaling events, and if disrupted could lead to
      decreased fertility and population decline. The in vitro sensitivity of amphibian
      oocytes and oocyte maturation to plant growth factor and widely used hormonal
      herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), was examined in this study to
      determine its potential impact on early development and possible contribution to
      the global amphibian decline. Progesterone, which acts through a membrane
      receptor, triggers meiotic maturation in full grown (stage VI) Xenopus oocytes,
      characterized by cytoskeletal reorganization, nuclear dissolution, chromosome
      condensation, and spindle formation. Biochemically, the Mos/MAPK/MPF signaling
      pathway is activated, in part dependent on translational activation of specific
      maternal mRNAs such as c-Mos. Light microscopy revealed unusual asymmetric
      morphotypes in oocytes exposed to 2,4-D alone characterized by a white spot and
      bulge, termed coning, in the animal pole where the germinal vesicle (nucleus)
      persisted intact. Treatment of oocytes with cytochalasin B, a microfilament
      inhibitor, blocked these morphotypes but nocodazole, a microtubule depolymerizing
      agent, did not. Confocal microscopy showed that 2,4-D, itself, caused substantial
      depolymerization of perinuclear microtubules. Importantly, 2,4-D blocked
      progesterone-induced maturation as measured by the lack of nuclear breakdown,
      confirmed by the lack of Mos expression, MPF activation, and cytoplasmic
      polyadenylation of cyclin B1 mRNA. However, Western blot analysis and U0126
      inhibitor studies showed that 2,4-D, either alone or in the presence of
      progesterone, induced MAPK phosphorylation through MAPKK. These results show that
      2,4-D disrupts oocyte cytoskeletal organization and blocks maturation while
      stimulating an independent MAPK signaling pathway.

PMID- 14694441
TI  - Capacitation of mammalian spermatozoa in vivo, with a specific focus on events in
      the Fallopian tubes.
AB  - This essay argues strongly that for those sperm cells involved in fertilisation,
      the process of capacitation represents an active and specific coordination within
      succeeding regions of the female tract and one whose completion is synchronised
      with the events of ovulation. Observations on the time-course of capacitation
      when spermatozoa are first exposed to the uterus and then progress to the
      Fallopian tubes indicate a synergistic influence of these adjoining portions of
      the female tract on the rate of capacitation. Three concepts on the control of
      capacitation are introduced to emphasise the importance of integration in vivo,
      namely that (1) completion of capacitation is a peri-ovulatory event, (2)
      suppression of completion of capacitation is an essential storage strategy during
      a long pre-ovulatory interval, and (3) the process of capacitation comes under
      the influence of local and systemic ovarian control mechanisms, especially the
      secretion of progesterone from Graafian follicles soon to ovulate. The last would
      act to coordinate the final maturation and meeting of male and female gametes.
      Despite the preceding points, the requirement for such integrated in vivo
      programming of sperm cell maturation can clearly be overridden in systems of
      culture. The most reasonable interpretation here would be that a microdrop of
      culture medium containing eggs, follicular cells and components of follicular
      fluid would to a considerable extent represent a post-ovulatory environment.
      Within such a preparation, there would be leaching of the sperm surface among the
      relatively vast and heterogeneous population of cells, and a proportion of
      spermatozoa could then respond to 'post-ovulatory signals', not least to
      molecular influences of the zona pellucida and vitelline products for completion
      of capacitation. Nonetheless, a physiologically meaningful interpretation of
      capacitation calls for a stepwise analysis of the dynamic interactions between
      sperm cell and female tract at successive stages between the uterus and ampullary
      isthmic junction.

PMID- 14694442
TI  - The molecular mechanism of sensitization to Fas-mediated apoptosis by 2
      methoxyestradiol in PC3 prostate cancer cells.
AB  - It is widely known that death receptor Fas-dependent apoptotic signals are
      associated with development of prostate cancer, but the key pathways involved in
      sensitivity to the apoptosis remain unclear. Here we investigated the molecular
      mechanism by which 2-methoxyestradiol (2-ME) effectively sensitizes a human
      prostate cancer cell line, PC3, to Fas-mediated apoptosis. 2-ME significantly
      inhibited nuclear factor-kappaB (NF-kappaB) activation and downregulated Fas
      associated death domain (FADD) protein interluekin-1beta-converting enzyme
      inhibitory protein (FLIP). Overexpression of the dominant negative mutant form of
      IkappaBalpha (d/n IkappaBalpha) or treatment with Ikappa kinase-specific
      inhibitor Bay117082 gave the same results, although the sensitizing effect was
      not as pronounced. A selective inhibitor of Akt phosphorylation, LY294002,
      accelerated formation of the death-inducing signaling complex (DISC) not only by
      FLIP reduction but also by enhancement of recruitment of the FADD to Fas, thereby
      sensitizing PC3 cells to apoptosis similar to the case with 2-ME stimulation.
      Moreover, we found that inhibition of 2-ME-induced extracellular signal-regulated
      kinase (ERK) activation by the upstream kinase inhibitor PD98059 significantly
      enhanced 2-ME-mediated suppression of Akt activation, resulting in much greater
      sensitization to apoptosis. Taken together, the present findings indicate that 2
      ME suppresses NF-kappaB/FLIP signaling and enhances DISC formation through
      inhibition of Akt, and that PC3 cells thereby are being sensitized to Fas
      mediated apoptosis and by a process closely associated with ERK.

PMID- 14694443
TI  - Expression of the p16INK4a gene and methylation pattern of CpG sites in the
      promoter region in rat tumor cell lines.
AB  - Loss of p16(INK4a) protein expression has frequently been related to DNA
      methylation in association with gene silencing. Although the methylation status
      of exon1alpha for p16(INK4a) involvement in various cancers has been extensively
      analyzed, it has been pointed out that some inconsistencies existed in its
      relationship to gene silencing of p16(INK4a). In this study, we focused on the
      expression and methylation status in the regions of nt -478 to -201, containing a
      putative TATA box (nt -401 to -396), and nt -233 to 26, both in a recently cloned
      5' upstream region of rat p16(INK4a). We showed that rat lung adenocarcinoma
      RLCNR did not express the p16(INK4a) gene, whereas rat osteosarcoma COS1NR and
      malignant fibrous histiocytoma MFH1NR both expressed it at levels similar to
      normal fibroblasts, even though the region of nt -233 to 26 was hypermethylated
      in COS1NR rather than RLCNR. In contrast, the CpG islands near the putative TATA
      box region were consistently methylated in RLCNR, but not in COS1NR and MFH1NR,
      as well as in normal fibroblasts. Treatment with 5-aza 2'-deoxycytidine induced
      expression of p16(INK4a) gene in RLCNR after 48 h, but no changes were observed
      in COS1NR and MFH1NR. The results indicated that methylation of CpG islands near
      a TATA box region played a critical role for gene silencing of the rat p16(INK4a)
      gene, rather than that of other regions.

PMID- 14694444
TI  - Antisense blocking of BRCA1 enhances sensitivity to plumbagin but not tamoxifen
      in BG-1 ovarian cancer cells.
AB  - Previous studies have shown that reduction in BRCA1 mRNA and protein can result
      in increased proliferation of BG-1 ovarian cancer cells in both in vitro and in
      vivo conditions, suggesting that BRCA1 may normally act as a growth inhibitor in
      these cells. Also, there are other reports that suggest that wild-type BRCA1
      protein may repress estrogen receptor (ER) function either directly or
      indirectly. However, response to antiestrogen drugs in BRCA1-blocked ER-positive
      ovarian cancer cells has not been reported, and this served as the rationale for
      this study. We analyzed the effect of tamoxifen, emodin, and plumbagin in BRCA1
      blocked ER-positive BG-1 ovarian cancer cells. For all three drugs, BRCA1-blocked
      cells were more sensitive than the corresponding control cells as assessed by MTT
      assay; however, only plumbagin showed a statistically significant difference in
      mean viability (P < 0.05). All three drugs induced loss of mitochondrial membrane
      potential (DeltaPsi(m)), nuclear condensation, DNA fragmentation, and
      morphological changes, as observed after 6 h of drug treatment, suggesting
      apoptosis induction in both BRCA1-blocked and control cells. However, apoptosis
      induction was greater in BRCA1-blocked cells, the efficacy being in the order of
      plumbagin > tamoxifen > emodin. The dose of plumbagin needed to kill 50% was 5
      microM in the control cells and 2.68 microM for the BRCA1-blocked cells,
      indicating that the latter was about twofold more sensitive to plumbagin than the
      wild-type cells. This throws light on the fact that plumbagin may have
      chemotherapeutic potential as an anticancer agent in BRCA1-mutated ovarian cancer
      patients.

PMID- 14694445
TI  - CHFR-associated early G2/M checkpoint defects in breast cancer cells.
AB  - Cell division is a highly regulated process. Checkpoints can halt cell-cycle
      progression due to adverse conditions such as misalignment of chromosomes to
      prevent missegregation. The search for new regulators of the cell cycle revealed
      the mitotic checkpoint gene CHFR (checkpoint with forkhead-associated and ring
      finger). CHFR coordinates an early mitotic phase by delaying chromosome
      condensation in response to a mitotic stress. Because aneuploidy and chromosome
      instability are common in malignant breast tumors, we screened 24 breast cancer
      cell lines for CHFR expression and demonstrated that 50% (12 of 24) of breast
      cancer cell lines had low CHFR levels. Expression of CHFR was reactivated with
      the demethylating agent 5-aza-2'-deoxycytidine (5-aza-dC) in two low-CHFR
      expressing cell lines. Eleven of these 12 (92%) low-CHFR-expressing cell lines
      had an unusually high number of condensed chromosomes and high mitotic indices in
      response to nocodazole treatment. Transfection of CHFR in one of these cancer
      cell lines lowered the mitotic index after nocodazole treatment. In conclusion,
      our data suggested that low CHFR expression associated with high mitotic indices
      in response to nocodazole treatment were common in the breast cancer cell lines
      studied. Additional flow cytometry studies and analysis of a protein that
      interacts with CHFR in vitro, polo-like kinase 1 (PLK1), suggests that this CHFR
      associated early G(2)/M checkpoint is complex, involving additional, as yet
      unidentified, proteins. Further analysis of CHFR in breast cancer cells will be
      important for understanding the complex mechanisms leading to aneuploidy and
      chromosomal instability observed in breast cancer.

PMID- 14694446
TI  - Adhesion, migration, transcriptional, interferon-inducible, and other signaling
      molecules newly implicated in cancer susceptibility and resistance of JB6 cells
      by cDNA microarray analyses.
AB  - Relative expression levels of 9500 genes were determined by cDNA microarray
      analyses in mouse skin JB6 cells susceptible (P+) and resistant (P-) to 12-O
      tetradecanoyl phorbol-13 acetate (TPA)-induced neoplastic transformation. Seventy
      four genes in 6 functional classes were differentially expressed: (I)
      extracellular matrix (ECM) and basement membrane (BM) proteins (20 genes). P+
      cells express higher levels than P- cells of several collagens and proteases, and
      lower levels of protease inhibitors. Multiple genes encoding adhesion molecules
      are expressed preferentially in P- cells, including six genes implicated in axon
      guidance and adhesion. (II) Cytoskeletal proteins (13 genes). These include actin
      isoforms and regulatory proteins, almost all preferentially expressed in P-
      cells. (III) Signal transduction proteins (12 genes). Among these are Ras-GTPase
      activating protein (Ras-GAP), the deleted in oral cancer-1 and SLIT2 tumor
      suppressors, and connexin 43 (Cx43) gap junctional protein, all expressed
      preferentially in P- cells. (IV) Interferon-inducible proteins (3 genes). These
      include interferon-inducible protein (IFI)-16, an Sp1 transcriptional regulator
      expressed preferentially in P- cells. (V) Other transcription factors (4 genes).
      Paired related homeobox gene 2 (Prx2)/S8 homeobox, and retinoic acid (RA)
      regulated nur77 and cellular retinoic acid-binding protein II (CRABPII)
      transcription factors are expressed preferentially in P- cells. The RIN-ZF Sp
      transcriptional suppressor exhibits preferential P+ expression. (VI) Genes of
      unknown functions (22 sequences). Numerous mesenchymal markers are expressed in
      both cell types. Data for multiple genes were confirmed by real-time PCR.
      Overall, 26 genes were newly implicated in cancer. Detailed analyses of the
      functions of the genes and their interrelationships provided converging evidence
      for their possible roles in implementing genetic programs mediating cancer
      susceptibility and resistance. These results, in conjunction with cell wounding
      and phalloidin staining data, indicated that concerted genetic programs were
      implemented that were conducive to cell adhesion and tumor suppression in P-
      cells and that favored matrix turnover, cell motility, and abrogation of tumor
      suppression in P+ cells. Such genetic programs may in part be orchestrated by Sp
      , RA-, and Hox-transcriptional regulatory pathways implicated in this study.

PMID- 14694447
TI  - Continuing medical edu-mercials.

PMID- 14694448
TI  - Cesarean section: does it really prevent the development of postpartum stress
      urinary incontinence? A prospective study of 363 women one year after their first
      delivery.
AB  - AIMS: Stress urinary incontinence (SUI) in young women is usually the result of
      pelvic floor injury during vaginal delivery. Whether cesarean section delivery
      may prevent such injury is questionable. We undertook a prospective study to
      compare the prevalence of SUI among primiparae 1 year after spontaneous vaginal
      delivery versus elective cesarean section, or cesarean section performed for
      obstructed labor. METHODS: Three hundred and sixty-three consecutive primiparae
      were recruited immediately after delivery and were followed for 1 year. Women
      were asked upon recruitment whether they had ever experienced SUI before
      pregnancy. Those who had SUI before pregnancy were excluded. Thus, only cases of
      de novo childbirth-associated SUI were analyzed. Patients were divided into three
      subgroups according to the mode of delivery: spontaneous vaginal delivery (n =
      145), elective cesarean section (n = 118), and cesarean section performed for
      obstructed labor (n = 100). Patients who underwent elective cesarean section were
      not given a trial of labor. Cesarean sections for obstructed labor were performed
      at a mean cervical dilatation of 8.7 +/- 1.6 cm and arrest of 184 +/- 24 min.
      Prevalence, frequency, and severity of postpartum SUI, as well as demographic and
      obstetric parameters, were analyzed in each subgroup. RESULTS: The three
      subgroups were comparable with respect to maternal age, weight, and height.
      Prevalence of postpartum SUI was similar after spontaneous vaginal delivery
      (10.3%) and cesarean section performed for obstructed labor (12%). However, SUI
      was significantly less common following elective cesarean section with no trial
      of labor (3.4%, P < 0.05). Approximately half of the symptomatic patients in each
      subgroup reported either moderate or severe symptoms, however, only 15-18%
      expressed their desire for further evaluation. CONCLUSIONS: Prevalence of
      postpartum SUI is similar following spontaneous vaginal delivery and cesarean
      section performed for obstructed labor. It is quite possible that pelvic floor
      injury in such cases is already too extensive to be prevented by surgical
      intervention. Conversely, elective cesarean section, with no trial of labor, was
      found to be associated with a significantly lower prevalence of postpartum SUI.
      Whether the prevention of pelvic floor injury should be an indication for
      elective cesarean section is yet to be established.

PMID- 14694449
TI  - Surgical complications and medium-term outcome results of tension-free vaginal
      tape: a prospective study of 313 consecutive patients.
AB  - OBJECTIVE: A prospective study was undertaken to examine the incidence of
      surgical complications and medium-term outcomes of tension-free vaginal tape
      (TVT) surgery in a large, heterogeneous group of stress-incontinent women.
      METHODS: Surgery was tailored according to preoperative clinical and urodynamic
      findings: stress-incontinent women underwent TVT surgery, whereas those with
      concomitant urogenital prolapse underwent combined TVT and prolapse repair. Post
      operatively the patients were scheduled for evaluation at 1, 3, 6, and 12 months,
      and annually thereafter. All underwent urodynamics at 3 months post-operatively.
      RESULTS: Three hundred and thirteen consecutive patients were prospectively
      studied. The mean follow-up period was 21.4 +/- 13.5 months. Sixteen (5.1%) cases
      of intravesical passage of the prolene tape occurred in our series, two of which
      were diagnosed at 3 and 15 months post-operatively. Eight (2.5%) patients had
      post-operative voiding difficulties, necessitating catheterization for more than
      7 days. However, transvaginal excision of the tape was required in one case only.
      Vaginal erosion of the tape was diagnosed in four (1.3%) patients, all of whom
      were successfully treated by local excision of the eroded tape. Outcome analysis
      was restricted to 241 consecutive patients with at least 12 months of follow-up.
      Subjectively, 16 (6.6%) patients had persistent mild stress urinary incontinence,
      although urodynamics revealed asymptomatic sphincteric incontinence in 17 (7%)
      other patients. De-novo urge incontinence developed post-operatively in 20 (8.3%)
      patients. CONCLUSIONS: The TVT procedure is associated with good medium-term cure
      rates, however, it is not free of troublesome complications and the patients
      should be informed accordingly. Only well-trained surgeons, familiar with pelvic
      anatomy, surgical alternatives, and endoscopic techniques should perform the
      operation.

PMID- 14694450
TI  - Opening detrusor pressure and the influence of age on success following
      colposuspension.
AB  - OBJECTIVE: Women with urodynamic stress incontinence (USI) have lower opening and
      closing detrusor pressures than women without USI. This study was undertaken to
      determine whether a change occurs in opening and closing detrusor pressures after
      colposuspension, whether cure is associated with change, and whether age
      influences cure. DESIGN: Retrospective cohort study. SETTING: Tertiary referral
      urogynaecology department. PARTICIPANTS: Consecutive women who had undergone
      colposuspension between 1998-2000 and 1993-1995. METHODS: Pre- and post-operative
      urodynamic records were reviewed. Eighty eight women were included. Objective
      cure was defined as an absence of USI and subjective cure as an absence of
      symptoms of stress incontinence. RESULTS: Mean age was 52.4 (11.0) years. Sixty
      nine percent (61/88) were objectively cured and 48% (42/88) were subjectively
      cured. Postoperatively, opening detrusor pressure increased (P = 0.0001) and
      maximum flow rate decreased (P= 0.0464) in women objectively cured but these
      parameters did not change in the not cured group (P > 0.05). Women had a 4.5
      times higher chance of failed surgery if post-op opening detrusor pressure was <
      or =20 cmH2O (P = 0.035). Opening detrusor pressure declined with age (P < 0.001)
      and women who were objectively cured were on average almost 7 years younger (P =
      0.0330). CONCLUSIONS: Increase in opening detrusor pressure occurs only in women
      who are cured following colposuspension. Change in opening detrusor pressure is
      dependent on age and objective cure is higher in younger women. The effects of
      ageing on sub-urethral supports might explain why surgery is more likely to fail
      in older women.

PMID- 14694451
TI  - Observations on the function of the female urethra: II: Relation between maximum
      urethral closure pressure at rest and the degree of urethral incompetence.
AB  - AIMS: To study the relation between maximum urethral closure pressure (MUCP) at
      rest and the degree of urethral incompetence in the female. PATIENTS AND METHODS:
      Two hundred fifty five patients aged 20 years or older, with stable bladders on
      multichannel urodynamics, without known neurological pathology, and with no
      previous history of pelvic or anti-incontinence surgery were included in the
      study. Resting urethral pressure profile (UPP) and the grade of urethral
      incompetence was registered. RESULTS: Mean age of the group was 45.6+/-12.7
      years; mean MUCP was 62.7+/-28.5 cm of water. There was a statistically
      significant difference in the MUCP when the different grades of urethral
      incompetence were compared to each other, the higher grades being associated with
      a lower maximal closure pressure. CONCLUSIONS: This study demonstrates that there
      is a highly significant relationship between MUCP and between all grades of
      urethral incompetence. This supports previous observations that MUCP decreases
      when abdominal leak point pressure (ALPP) is low and that this might be secondary
      to some mechanical failure in the pressure transmission from the abdominal cavity
      to the urethra. Studies should never compare continent to incontinent cohorts
      without considering their ALPP because in doing so they are comparing groups that
      are functionally heterogeneous.

PMID- 14694452
TI  - Observations on the function of the female urethra: III: An overview with special
      reference to the relation between urethral hypermobility and urethral
      incompetence.
AB  - AIMS: To analyze the relation between urethral hypermobility and urethral
      incompetence, and to summarize the interdependence between maximum urethral
      closure pressure (MUCP), urethral hypermobility, and urethral incompetence.
      PATIENTS AND METHODS: A group of 255 patients was selected from a large bank of
      cases. Inclusion criteria were age 20 years or above, no neurological disease,
      stable bladder, and no previous incontinence surgery or hysterectomy. The degree
      of hypermobility (cysto-urethrocele) and the degree of urethral incompetence
      (abdominal leak point pressure (ALPP)) were determined. Statistical analyses
      between urethral hypermobility and incompetence were performed with Spearman's
      correlation and the Jonckherre-Terpstra test. RESULTS: The Spearman's rank
      correlation test showed a statistically significant relation between urethral
      hypermobility and the degree of urethral incompetence (P = 0.0049). CONCLUSIONS:
      The statistically significant relation between urethral incompetence and
      hypermobility suggests that urethral incompetence will increase as the degree of
      urethral hypermobility does. Optimal conditions for urinary continence include a
      high maximum urethral closure pressure, absence of hypermobility, and a low
      degree of urethral incompetence. This last factor is assured by a strong support
      underneath the urethra permitting compression of the latter during straining.
      Failure of the urethral closure mechanism is highly probable with a diminished
      maximum closure pressure accompanied by urethral hypermobility often associated
      with a high degree of urethral incompetence. Clinically significant urinary
      incontinence may appear in many intermediate circumstances between these two
      extreme states, but stress urinary incontinence is essentially an activity
      related phenomenon.

PMID- 14694453
TI  - Measuring the severity of stress urinary incontinence using the Incontinence
      Impact Questionnaire.
AB  - AIMS: Questionnaires, including the Incontinence Impact Questionnaire (IIQ), have
      been used to assess the severity of urinary incontinence in clinical trials.
      However, the summed score derived from the IIQ does not have any inherent
      clinical meaning. Also, a summed score does not have interval properties,
      complicating the interpretation of changes in severity. The purpose of this study
      is to test the hypothesis that incontinence-related disability is a measurable
      variable and that the IIQ can measure that variable accurately. METHODS: We used
      Rasch analysis, a logistic regression technique, to estimate an interval scale of
      incontinence severity. Rasch analysis is based on the mathematical assumption
      that each subject's response to any given item is a function of (a) the
      individual's inherent level of disability and (b) the inherent difficulty of that
      item. RESULTS: Twenty-seven women with urodynamic stress urinary incontinence
      (USUI) completed the IIQ. Using Rasch analysis, we found that women with USUI had
      the most difficulty engaging in "physical recreational activities" and the least
      difficulty participating in "relationship with family." We also assessed the
      ability of the IIQ to discriminate between individuals with respect to disease
      severity. We found that most of the items in the IIQ are useful for
      discriminating incontinence severity among women with mild or moderate
      incontinence, but very few IIQ items distinguish among women with severe
      incontinence. CONCLUSIONS: Our results have important implications for clinical
      trials using the IIQ: among women treated for severe incontinence, the standard
      IIQ summed score will underestimate the magnitude of any change in incontinence
      severity.

PMID- 14694454
TI  - Assessment of pelvic organ descent by use of functional cine-MRI: which reference
      line should be used?
AB  - BACKGROUND AND AIMS: So far there is no agreement between clinical and
      radiological measurements and reference points for the quantification of pelvic
      organ descent in women. The aim of this study was to find out which of three
      reference lines on functional cine-magnetic resonance imaging (MRI) correlates
      best with the respective clinical diagnoses. METHODS: We retrospectively
      evaluated the functional cine-MRI studies of 41 asymptomatic volunteers. Our
      golden standard was the results of the clinical examination using the
      International Continence Society (ICS)-score. On MRI, we measured the distance of
      the bladder-neck, distal edge of cervix/posterior fornix, and the most
      ventrocaudal point of the ventral rectal wall, respectively, to the pubococcygeal
      line (PCL), the horizontal tangent of the inferior rim of the pubic bone, and the
      line drawn through the long axis of the pubic bone. The results were correlated
      with the respective clinical findings using descriptive analysis alone. RESULTS:
      The volunteers either showed a Stage 0 (16 cases), Stage I (12 cases), or a Stage
      II (13 cases) organ descent on clinical examination with 10 women (24.4%) having
      a pathological ICS-score in the anterior, 15 women (36.1%) in the superior, and 4
      women (9.8%) in the posterior compartment. On functional MRI the best correlation
      with the clinical results was achieved using the PCL for the anterior compartment
      (22.0%), the PCL with an offset of +3 cm for the superior (36.6%), and the
      hymenal line (HL) for the posterior compartment (9.8%). CONCLUSIONS: Organ
      descent on functional cine-MRI cannot be described using only one reference line.
      In order to optimize clinical exploitation of functional MRI of the pelvic floor
      a consensus regarding imaging protocols and evaluation criteria should be aimed
      for.

PMID- 14694455
TI  - The association between overactive bladder symptoms and objective parameters from
      bladder diary and filling cystometry.
AB  - AIMS: To investigate the association between overactive bladder symptoms and
      objective parameters from the bladder diary and conventional filling cystometry.
      METHODS: We reviewed the records of the 95 consecutive patients presenting at our
      center for urodynamic investigation. These women were asked to self-complete a
      questionnaire and a bladder diary for 48 hr. Urogenital symptoms and disease
      specific quality of life were assessed with standardized questionnaire, namely
      the Dutch version of the Urogenital Distress Inventory (UDI) and the Incontinence
      Impact Questionnaire (IIQ). RESULTS: The frequency symptom as well as the urge
      incontinence symptom is significantly associated with the presence of detrusor
      overactivity. In univariate analysis both frequency and urgency symptoms are
      associated with lower micturition and bladder sensation volumes. In multivariate
      (ANOVA) analysis, the frequency symptom is associated with a higher 24-hr
      frequency, lower maximum volume voided, and mean volume voided per micturition on
      the bladder diary. It is also associated with lower sensation volumes on the
      filling cystometry. CONCLUSIONS: Of the four symptoms that are currently
      considered to be part of the overactive bladder syndrome, the frequency symptom
      is the best associated with objective parameters from the bladder diary, filling
      cystometry, and with the occurrence of detrusor overactivity. Therefore, we would
      like to suggest that reporting subjective symptoms frequency is obligatory for
      considering one to have an overactive bladder.

PMID- 14694456
TI  - Urgency of voiding and abdominal pressure transmission in women with mixed
      urinary incontinence.
AB  - AIMS: To ascertain whether abdominal pressure transmission (a.p.t.) to the
      urethra would be affected by urgency of voiding in women with mixed urinary
      incontinence. METHODS: We urodynamically assessed 80 consecutive women. Group 1
      (n = 40), with stress incontinence, had stable bladders and no urgency. Group 2
      (n = 40), with mixed (stress + urge) incontinence and overactive bladders, were
      split into Groups 2A (n = 20) and 2B (n = 20) according to the delay time of
      urgent void at cystometry (CMG) equating at least 2 min (taken as an index of
      moderate urgency) or, respectively, less than 2 min (taken as an index of severe
      urgency). Nonparametric statistics checked for significant differences in a.p.t.
      and in pelvic floor (peri-urethral) muscle strength level. We defined a.p.t. at
      stress (cough) urethral pressure profilometry (UPP) by the pressure transmission
      ratio (PTR). Pelvic floor muscle strength was defined at "holding" UPP by the
      maximum urethral pressure developed during attempts "to hold urine" (hMUP).
      RESULTS: PTR was reduced in all women, but PTR (and hMUP) proved relatively
      higher in Group 2, though nonsignificantly different values of PTR (and hMUP)
      were seen in Groups 2B and 1. CONCLUSIONS: Transmission of abdominal pressure to
      the urethra was reduced in all of the incontinent women. The mixed incontinence
      group, however, had a relatively less reduced (active component of) a.p.t., most
      likely dependent on a greater pelvic floor (peri-urethral) muscle strength level
      secondary to frequent contractions in response to urgency. Yet, of the same mixed
      incontinence patients, those with the most severe urgency degrees had relatively
      low pelvic floor (peri-urethral) muscle strength levels (eventually resulting
      from muscle fatigue? or primarily due to peri-urethral tissue atrophy?), which
      prevented (the active component of) a.p.t. from increasing.

PMID- 14694457
TI  - Clinical efficacy of tolterodine with or without a simplified pelvic floor
      exercise regimen.
AB  - OBJECTIVES: To investigate whether the combination of tolterodine plus (Tp) a
      simple pelvic floor muscle exercise (PFME) program would provide improved
      treatment benefits compared with tolterodine alone (Ta) in patients with symptoms
      of overactive bladder (OAB). METHODS: After a 1-2 week run-in period, 480
      patients with symptoms of urinary frequency (> or =8 micturitions/24 hr),
      urgency, and urge incontinence (> or =1 episode/24 hr), were randomized to
      receive tolterodine 2 mg bid with or without a simple PFME program for 24 weeks
      in this multinational study. Treatment efficacy was assessed by comparing the
      change from baseline in 3-day micturition diary recordings. RESULTS: After 24
      weeks' treatment, in the Ta group the urgency episodes reduced from mean of 4.1
      to 1.5 (83% reduction) while in the Tp group the urgency episodes reduced from
      4.2 to 2.1 (78.7% reduction). Mean incontinence episodes per day decreased from
      3.21 (standard deviation (SD) 3.4) to 0.95 (SD 1.9) in Ta group and from 3.44 (SD
      3.4) to 1.25 (SD 2.7) in the Tp group. Similarly, the number of micturition/24 hr
      were significantly reduced, from 12.78 to 9.20 (27.3% reduction) in the Ta group
      and from 11.87 to 9.29 (23% reduction) in the Tp group. There was an improvement
      in the patients' perception of urinary symptoms in 85.9% of patients on Ta and
      81.7% patients on Tp PFME. There were no statistically significant differences
      between the groups with regard to any of the outcome parameters. CONCLUSIONS:
      Tolterodine therapy for 24 weeks results in significant improvement in urgency,
      frequency, and incontinence, however, no additional benefit was demonstrated for
      a simple PFME program.

PMID- 14694458
TI  - Primary nocturnal enuresis persistent to adulthood, functional evaluation.
AB  - INTRODUCTION AND OBJECTIVES: The incidence of nocturnal enuresis (NE) in adults
      (over 18 years of age) ranges from 0.5 to 2% for most authors. NE is a
      multifactorial disease. Lack of circadian rhythm of antidiuretic hormone (ADH) is
      one of the commonly accepted causes, however, disorders affecting bladder
      function is another important pathophysiologic factor that has not been settled.
      The target of the present study is to define bladder function in adults having
      persistent NE. METHODS: Fifty two adult patients were included. Mean age was 23.6
      +/- 6.9 years. All of them had primary NE persistent to adulthood. No treatment
      was received within 2-7 days prior to the urodynamic examination. All of them had
      intact neuro-urological examination. Filling (in all patients) and voiding
      cystometry (in 29 patients) were carried out, using 8 F urodynamic and 8 F rectal
      catheters. Pressure flow analysis was interpreted using Schafer's nomogram.
      RESULTS: Overall mean maximum cystometric capacity was 419.2 +/- 142 ml, mean
      bladder compliance was 51.3 +/- 39.7 ml/cmH2O. In males (n=25), mean maximum
      cystometric capacity was 453 +/- 173 ml and compliance was 56 +/- 42 ml/cmH2O,
      while in females (n=27), mean capacity was 388 +/- 98 ml and compliance was 46.7
      +/- 36.7 ml/cmH2O. Twenty patients had detrusor instability (38.5%). Twelve out
      of 27 (44.4%) females had instability while only 8 out of 25 (32%) males had the
      same finding. Differences relevant to maximum bladder capacity and compliance
      between the patients with and without instability were significant (P<0.0001).
      Mean detrusor opening pressure was 55.3 +/- 25 cmH2O, mean detrusor pressure at
      maximum flow and maximum detrusor pressure, were 53.5 +/- 21 and 78.9 +/- 35
      cmH2O respectively. CONCLUSIONS: Urodynamic studies in adults with persistent NE
      reveals a relatively high incidence of instability, normal capacity and
      compliance. The presence of instability was associated with smaller bladder and
      poorer compliance and with diurnal urgency. Voiding bladder function in adult
      enuretics was found to be normal.

PMID- 14694459
TI  - Acupuncture reflexotherapy in the treatment of sensory urgency that persists
      after transurethral resection of the prostate: a preliminary report.
AB  - AIMS: In this study, we wanted to evaluate whether acupuncture reflexotherapy is
      able to treat the sensory irritative components of LUTS (lower urinary tract
      symptoms) that persist after transurethral resection of the prostate. METHODS: We
      have evaluated 42 patients, randomly selected into three groups: 14 patients
      received placebo, 15 patients received oxybutynin, and 13 patient were treated
      with electrostimulation by acupuncture reflexotherapy. RESULTS: Before treatment,
      the mean maximum flow rate (Qmax) was 21.0 +/- 3.2 mL/sec, the mean International
      Prostate Symptom Score (I-PSS) score was 12.9 +/- 4.2, the mean I-PSS Quality of
      Life (IPSS QoL) score was 3.6 +/- 1.2. At the first check-up performed after 3
      months, we could observe that the I-PSS and QoL scores were 12.6 +/- 4.3 and 3.8
      +/- 1.3 in the group who received placebo; the scores decreased to 11.1 +/- 3.2
      and to 3.1 +/- 1.0, respectively, in the 15 patients treated with oxybutynin and
      decreased to 6.1 +/- 2.6 and 1.3 +/- 1.1, respectively, in the 13 patients who
      underwent acupuncture reflexotherapy. At 1-year follow-up, these parameters were
      practically similar. The voiding diaries allowed us to deduce that the average
      number of daytime voidings decreased by 8% in patients who received oxybutynin
      and decreased by 20% in 13 patients who underwent reflexotherapy; the average
      number of nocturnal micturitions decreased by approximately 20% and 60%,
      respectively, in patients who received oxybutynin and reflexotherapy.
      CONCLUSIONS: This study has pointed out that acupuncture reflexotherapy has a
      real benefit in patients with sensory urgency that persists after transurethral
      resection of the prostate.

PMID- 14694460
TI  - A review of non-invasive electro neuromodulation as an intervention for non
      neurogenic bladder dysfunction in children.
AB  - AIMS: The use of electrotherapeutics to improve filling and emptying dysfunction
      of the adult bladder has been well established, however the practice in children
      is less well known. The purpose of this review is to summarize the rationale
      behind the use of electro neuromodulation in children, examine the reported
      efficacy of the intervention for different presentations of dysfunction, and
      establish the current limitations to knowledge and practice. MATERIALS AND
      METHODS: A modified systematic review was carried out on all Medline studies
      identified as considering the use of electrotherapy or neuromodulation in
      children with bladder problems. Literature relating to use of this approach in
      adults was also searched in order to present current understanding of the
      treatment rationale and modes of application. RESULTS: A Medline search and
      handsearch of relevant conference proceedings revealed six studies of
      neuromodulation in children with non-neurogenic bladder dysfunction. There were
      no reports of the intervention in children with isolated pelvic floor
      dyssynergia, irritative symptoms, structural changes predisposing the pelvic
      floor to weakness, or monosymptomatic nocturnal enuresis. One report of the
      favorable effect of neuromodulation on gut dysmotility was identified. Study
      design and quality generated level 4 evidence. Positive post-intervention changes
      reported included: increased bladder capacity, decreased severity of urge,
      improved continence, and decrease frequency of urinary tract infection.
      Significant improvement in the urodynamic parameters of bladder compliance,
      number of uninhibited contractions, and bladder volume at first detrusor
      contraction were also reported. CONCLUSIONS: There are clear benefits from the
      use of electroneuromodulation in children with differing forms of voiding
      dysfunction. The treatment approach is independent of cognitive and
      pharmacological therapy, is minimally invasive, and free of side effects. To
      date, there are no clinical variables that reliably predict efficacy of
      electrotherapy in the various presentations of over and under active detrusor,
      sphincter dyssynergia, or irritative symptoms.

PMID- 14694461
TI  - Lower urinary tract dysfunctions in patients with spinal cord tumors.
AB  - AIMS: The objective of this study was to elucidate the incidence and
      pathophysiology of lower urinary tract dysfunctions (LUTS) in patients with
      spinal cord tumors. METHODS: Urinary questionnaire and urodynamic studies were
      done in 76 patients with spinal cord tumors. RESULTS: The patients included 56
      with cervical-thoracic (C1 to T11) and 20 with lumbosacral tumors. The
      lumbosacral tumors consisted of 12 epiconus/conus medullaris (below T11) and 8
      cauda equina tumors. These tumors were further subdivided into intramedullary,
      intradural extramedullary, and dumbbell-type. More than 83% of the patients had
      urinary symptoms. Patients with cervical-thoracic tumors commonly had voiding
      symptoms (75%). Detrusor hyperreflexia (39%), and detrusor areflexia on voiding
      (21%) were the main urodynamic features. Patients with epiconus/conus medullaris
      tumors commonly had voiding symptoms as well (58%), but decreased urge to void
      (50%), detrusor-sphincter dyssynergia (42%), and detrusor areflexia on voiding
      (32%) were the main features. Patients with cauda equina tumors commonly had
      storage symptoms (88%), of which sensory urgency was most common (63%). Severe
      LUTS occurred in the epiconus/conus medullaris tumors and in the intramedullary
      tumors. These dysfunctions tended to appear late and rarely appeared as the
      initial symptom in the course of the disease. There was no significant
      relationship between neurologic abnormalities and LUTS. Urodynamics showed that
      spinal cord tumors cause a variety of LUTS, depending on the location and the
      type of the tumor. CONCLUSION: Spinal cord tumors are commonly accompanied by
      LUTS. Clinical and urodynamic evaluation is crucial to diagnosis and management
      since there is little relationship between symptoms and findings.

PMID- 14694462
TI  - Theoretical analysis of the effects of viscous losses and abdominal straining on
      urinary outlet function.
AB  - AIMS: The aim of this study was to theoretically explore the relationship between
      the tube law (TL) of the urethra and the pressure-flow (p-Q) relationship during
      micturition. The understanding of this relation is important for the evaluation
      of outlet obstruction by urodynamic interpretation of p-Q plots. METHODS: We
      simulated the outlet function by a lumped theoretical model, and suggested how
      the TL can be used to quantitatively predict the p-Q relationship of the system.
      Our analysis considered the relation between the TL and the steady state p-Q plot
      for various TLs including the hysteresis of the pressure-area relationship.
      RESULTS AND CONCLUSIONS: The inclusion of pressure losses distal to the flow
      controlling zone and experimentally measured p-A relations of the urethra in the
      model lead to the predictions that flow in the flow controlling zone is not
      always critical but is often in the sub-critical range, that an increase in
      abdominal pressure can increase the flow under certain conditions, and that
      hysteresis in the pressure-area relation is correlated to the hysteresis in the p
      Q plot.

PMID- 14694467
TI  - New mass spectrometric methods for the quantification of protein-ligand binding
      in solution.

PMID- 14694468
TI  - Direct oxidation of azides to nitro compounds.

PMID- 14694469
TI  - The evolution of dip-pen nanolithography.
AB  - The ability to tailor the chemical composition and structure of a surface on the
      1-100 nm length scale is important to researchers studying topics ranging from
      electronic conduction, to catalysis, to biological recognition in nanoscale
      systems. Dip-pen nanolithography (DPN) is a new scanning-probe based direct-write
      tool for generating such surface-patterned chemical functionality on the sub-100
      nm length-scale, and it is a technique that is accessible to any researcher who
      can use an atomic force microscope. This article introduces DPN and reviews the
      rapid growth of the field of DPN-related research over the past few years. Topics
      covered range from the development of new classes of DPN-compatible chemistry, to
      experimental and theoretical advances in the understanding of the processes
      controlling tip-substrate ink transport, to the implementation of micro-electro
      mechanical system (MEMS) based strategies for parallel DPN applications.

PMID- 14694470
TI  - A planning strategy for diversity-oriented synthesis.
AB  - In contrast to target-oriented synthesis (TOS) and medicinal or combinatorial
      chemistry, which aim to access precise or dense regions of chemistry space,
      diversity-oriented synthesis (DOS) populates chemical space broadly with small
      molecules having diverse structures. The goals of DOS include the development of
      pathways leading to the efficient (three- to five-step) synthesis of collections
      of small molecules having skeletal and stereochemical diversity with defined
      coordinates in chemical space. Ideally, these pathways also yield compounds
      having the potential to attach appendages site- and stereoselectively to a
      variety of attachment sites during a post-screening, maturation stage. The
      diverse skeletons and stereochemistries ensure that the appendages can be
      positioned in multiple orientations about the surface of the molecules. TOS as
      well as medicinal and combinatorial chemistries have been advanced by the
      development of retrosynthetic analysis. Although the distinct goals of DOS do not
      permit the application of retrosynthetic concepts and thinking, these foundations
      are being built on, by using parallel logic, to develop a complementary procedure
      known as forward-synthetic analysis. This analysis facilitates synthetic
      planning, communication, and teaching in this evolving discipline.

PMID- 14694471
TI  - Dynamics of ordered water in interfacial enzyme recognition: bovine pancreatic
      phospholipase A2.

PMID- 14694472
TI  - Synthesis of crystalline silicon tubular nanostructures with ZnS nanowires as
      removable templates.

PMID- 14694474
TI  - Synthesis of versatile chiral N,P ligands derived from pyridine and quinoline.

PMID- 14694475
TI  - Pi-conjugated oligo-(p-phenylenevinylene) rosettes and their tubular self
      assembly.

PMID- 14694473
TI  - Characterization of NovP and NovN: completion of novobiocin biosynthesis by
      sequential tailoring of the noviosyl ring.

PMID- 14694476
TI  - Silica-water reaction media: its application to the formation and ring opening of
      aziridines.

PMID- 14694477
TI  - Enantioselective synthesis of the spirotetracyclic carbon core of mangicols by
      using a stereoselective transannular Diels-Alder strategy.

PMID- 14694478
TI  - Kinetic resolution of epoxides by a C-C bond-forming reaction: highly
      enantioselective addition of indoles to cis, trans, and meso aromatic epoxides
      catalyzed by [Cr(salen)] complexes.

PMID- 14694479
TI  - Cubane [CuII4] cluster as a precursor for the preparation of a mixed-valent
      [CuII12CuI2] core.

PMID- 14694480
TI  - The complete delineation of the initiation, propagation, and termination steps of
      the carbomethoxy cycle for the carboalkoxylation of ethene by Pd-diphosphane
      catalysts.

PMID- 14694481
TI  - The mechanism of Bu3SnH-mediated homolytic aromatic substitution.

PMID- 14694482
TI  - Characterization of a dinuclear MnV=O complex and is efficient evolution of O2 in
      the presence of water.

PMID- 14694483
TI  - Design and fabrication of a flexible and self-supporting supramolecular film by
      hierarchical control of the interaction between hydrogen-bonded sheet assemblies.

PMID- 14694484
TI  - Electrophilic cleavage of one silicon-carbon bond of pentacoordinate
      tetraorganosilanes: synthesis of silalactones.

PMID- 14694485
TI  - Consecutive double 1,2-migration of two different groups in
      silyl(dichloromethyl)cuprates.

PMID- 14694486
TI  - Analysis of the spatial dimensions of fully aromatic dendrimers.

PMID- 14694488
TI  - A short, atom-economical entry to tetrahydroxanthenones.

PMID- 14694487
TI  - Rational design of nanostructured copper-zinc oxide catalysts for the steam
      reforming of methanol.

PMID- 14694489
TI  - Do quantum size effects control CO adsorption on gold nanoparticles?

PMID- 14694490
TI  - Coupling of methane and ammonia by dinuclear bimetallic platinum-coinage-metal
      cations PtM+.

PMID- 14694494
TI  - Pulmonary complications of chronic neuromuscular diseases and their management.
AB  - Chronic neuromuscular diseases may affect all major respiratory muscles groups
      including inspiratory, expiratory, and bulbar, and respiratory complications are
      the major cause of morbidity and mortality. Untreated, many of these diseases
      lead inexorably to hypercapnic respiratory failure, precipitated in some cases by
      chronic aspiration and secretion retention or pneumonia, related to impairment of
      cough and swallowing mechanisms. Many measures are helpful including inhibition
      of salivation, cough-assist techniques, devices to enhance communication, and
      physical therapy. In addition, ventilatory assistance is an important part of
      disease management for patients with advanced neuromuscular disease. Because of
      its comfort, convenience, and portability advantages, noninvasive positive
      pressure ventilation (NPPV) has become the modality of first choice for most
      patients. Patients to receive NPPV should be selected using consensus guidelines,
      and initiation should be gradual to maximize the chances for success. Attention
      should be paid to individual preferences for interfaces and early identification
      of cough impairment that necessitates the use of cough-assist devices. For
      patients considered unsuitable for noninvasive ventilation, invasive mechanical
      ventilation should be considered, but only after a frank but compassionate
      discussion between the patient, family, physician, and other caregivers.

PMID- 14694495
TI  - Threshold electrotonus in chronic inflammatory demyelinating polyneuropathy:
      correlation with clinical profiles.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by
      multifocal demyelination along the course of the nerves, and involvement of the
      intermediate segments may correlate with more severe demyelination associated
      with breakdown of the blood-nerve barrier. Threshold electrotonus was used to
      study whether altered membrane properties of the median nerve at the wrist
      (intermediate segment) are associated with clinical profiles in 21 CIDP patients.
      In response to hyperpolarizing conditioning stimuli, the threshold changes were
      significantly greater for CIDP patients than for normal controls (n = 49). The
      pattern was similar to that of 11 patients with Charcot-Marie-Tooth disease type
      1a, who exhibited abnormally high thresholds to hyperpolarizing currents. The
      abnormal threshold electrotonus was present in 48% of the CIDP patients and was
      associated with longer disease duration, more severe disability, poorer response
      to immune treatments, and slower nerve conduction velocities. Threshold
      electrotonus can be used to detect demyelination at the tested sites and may
      provide new information about pathophysiology and distribution patterns of
      demyelination in CIDP.

PMID- 14694496
TI  - Na+,K+-ATPase concentration and fiber type distribution after spinal cord injury.
AB  - Complete spinal cord injury (SCI) is characterized, in part, by reduced fatigue
      resistance of the paralyzed skeletal muscle during stimulated contractions, but
      the underlying mechanisms are not fully understood. The effects of complete SCI
      on skeletal muscle Na(+),K(+)-adenosine triphosphatase (ATPase) concentration,
      and fiber type distribution were therefore investigated. Six individuals (aged
      32.0 +/- 5.3 years) with complete paraplegia (T4-T10; 1-19 years since injury)
      participated. There was a significantly lower Na(+),K(+)-ATPase concentration in
      the paralyzed vastus lateralis (VL) when compared to either the subjects' own
      unaffected deltoid or literature values (from our laboratory, utilizing the same
      methodology) of VL Na(+),K(+)-ATPase concentration for the healthy able-bodied
      (141.6 +/- 50.0, 213.4 +/- 23.9, 339 +/- 16 pmol/g wet wt., respectively; P <
      0.05). There was also a significant negative correlation between the Na(+),K(+)
      ATPase concentration in the paralyzed VL and years since injury (r = -0.75, P <
      0.05). These findings are clinically relevant as they suggest that reductions in
      Na(+),K(+)-ATPase contribute to the fatigability of paralyzed muscle after SCI.
      Unexpectedly, the VL muscles of our subjects had a higher proportion of their
      area represented by type I fibers compared to literature values for the VL of the
      healthy able-bodied (52.6 +/- 25.3% vs. 36 +/- 11.3%, respectively; P < 0.05). As
      all our subjects had upper motor neuron injuries and, therefore, experienced
      muscle spasticity, our findings warrant further investigation into the
      relationship between muscle spasticity and fiber type expression after SCI.

PMID- 14694497
TI  - Muscle-fiber conduction velocity and electromyography as diagnostic tools in
      patients with suspected inflammatory myopathy: a prospective study.
AB  - Combinations of different techniques can increase the diagnostic yield from
      neurophysiological examination of muscle. In 25 patients with suspected
      inflammatory myopathy, we prospectively performed needle electromyography (EMG)
      and measured muscle-fiber conduction velocity (MFCV) in a single muscle, using a
      technique with direct muscle-fiber stimulation and recording. Results of MFCV
      were compared with final diagnosis, EMG, and needle muscle biopsy. Diagnostic
      accuracy of combined MFCV and EMG studies was 72%, compared to 60% for EMG alone.
      This improvement was due to a gain in specificity. The MFCV did not prove useful
      in discriminating inflammatory myopathy from other myopathies. Furthermore, we
      found a correlation of 92% between variability of MFCV and myopathic changes in
      muscle biopsy. We conclude that the utility of electrodiagnostic examination can
      be increased if EMG examination is combined with MFCV studies.

PMID- 14694498
TI  - Creatine monohydrate supplementation does not increase muscle strength, lean body
      mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1.
AB  - Creatine monohydrate (CrM) supplementation may increase strength in some types of
      muscular dystrophy. A recent study in myotonic muscular dystrophy type 1 (DM1)
      did not find a significant treatment effect, but measurements of muscle
      phosphocreatine (PCr) were not performed. We completed a randomized, double
      blind, cross-over trial using 34 genetically confirmed adult DM1 patients without
      significant cognitive impairment. Participants received CrM (5 g, approximately
      0.074 g/kg daily) and a placebo for each 4-month phase with a 6-week wash-out.
      Spirometry, manual muscle testing, quantitative isometric strength testing of
      handgrip, foot dorsiflexion, and knee extension, handgrip and foot dorsiflexion
      endurance, functional tasks, activity of daily living scales, body composition
      (total, bone, and fat-free mass), serum creatine kinase activity, serum
      creatinine concentration and clearance, and liver function tests were completed
      before and after each intervention, and muscle PCr/beta-adenosine triphosphate
      (ATP) ratios of the forearm flexor muscles were completed at the end of each
      phase. CrM supplementation did not increase any of the outcome measurements
      except for plasma creatinine concentration (but not creatinine clearance). Thus,
      CrM supplementation at 5 g daily does not have any effects on muscle strength,
      body composition, or activities of daily living in patients with DM1, perhaps
      because of a failure of the supplementation to increase muscle PCr/beta-ATP
      content.

PMID- 14694499
TI  - Neuromuscular expression of the BTB/POZ and zinc finger protein myoneurin.
AB  - Myoneurin belongs to the BTB/POZ and zinc finger protein family whose members
      have been implicated in regulatory functions of gene expression. Myoneurin has
      been identified in various tissues, but muscle is a privileged site of myoneurin
      gene transcription. We examined the neuromuscular expression of myoneurin during
      development and after axotomy. Myoneurin expression is developmentally regulated
      in mouse muscle and appeared to be associated with neuromuscular junctions during
      the late embryonic period. Myoneurin is located in and around synaptic myonuclei
      in mouse and human adult muscle. The expression of myoneurin is dysregulated
      after nerve section. Thus, the restricted myoneurin expression in synaptic
      myonuclei appeared to be controlled by muscle electrical activity. Myoneurin is
      identified within the peripheral condensed chromatin and the
      euchromatin/heterochromatin regions, and thus fulfills structural and expression
      criteria to represent a synaptic gene regulator.

PMID- 14694500
TI  - Peripheral neuropathy, episodic myoglobinuria, and respiratory failure in
      deficiency of the mitochondrial trifunctional protein.
AB  - Mitochondrial trifunctional protein (TFP) deficiency is a rare disorder of the
      fatty acid beta-oxidation cycle with heterogeneous phenotypes and occurs
      secondary to either alpha- or beta-subunit mutations. We characterized the
      neuromyopathic phenotype of TFP deficiency through adolescence or adulthood in 11
      patients, 8 with beta-subunit mutations and 3 with alpha-subunit mutations. Two
      independent clinical features occurred: infantile-onset progressive peripheral
      neuropathy and episodic exercise-, illness- or fasting-induced rhabdomyolysis
      accompanied by respiratory failure (in five patients). The combination of
      episodic rhabdomyolysis and peripheral neuropathy occurred in 10 of the 11
      patients. The neuromyopathic phenotype is common in TFP deficiency (11 of 27
      families from our cohort). Therefore, this disorder must be considered in the
      differential diagnosis of progressive peripheral neuropathy with or without
      episodic myoglobinuria.

PMID- 14694501
TI  - Exercise-induced gene expression in soleus muscle is dependent on time after
      spinal cord injury in rats.
AB  - Cycling exercise attenuates atrophy in hindlimb muscles and causes changes in
      spinal cord properties after spinal cord injury in rats. We hypothesized that
      exercising soleus muscle expresses genes that are potentially beneficial to the
      injured spinal cord. Rats underwent spinal cord injury at T10 and were exercised
      on a motor-driven bicycle. Soleus muscle and lumbar spinal cord tissue were used
      for messenger RNA (mRNA) analysis. Gene expression of brain-derived neurotrophic
      factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) was elevated
      11- and 14-fold, respectively, in soleus muscle after one bout of exercise
      performed 5 days after spinal cord transection. Also, c-fos and heat shock
      protein-27 (HSP27) mRNA abundance were increased 11- and 7-fold, respectively.
      When exercise was started 2 days after the injury, the changes in gene expression
      were not observed. By contrast, at 2 but not at 5 days after transection,
      expression of the HSP27 gene was elevated sixfold in the lumbar spinal cord,
      independent of exercise. Electromyographic activity in soleus muscles was also
      decreased at 2 days, indicating that the spinal cord was less permissive to
      exercise at this early time. Long-term exercise for 4 weeks attenuated muscle
      atrophy equally well in rats started at 2 days or 5 days after injury. We
      conclude that BDNF and GDNF released from exercising muscle may be involved in
      exercise-induced plasticity of the spinal cord. Furthermore, the data suggest
      that the lumbar spinal cord undergoes time-dependent changes that temporarily
      impede the ability of the muscle to respond to exercise.

PMID- 14694502
TI  - Intracarpal steroid injection is safe and effective for short-term management of
      carpal tunnel syndrome.
AB  - A double-blinded placebo-controlled trial was performed to evaluate the use of
      steroid injections beneath the transverse carpal ligament in the treatment of
      carpal tunnel syndrome (CTS) refractory to nonsurgical therapy. Forty-three
      patients received 6 mg betamethasone and lidocaine and 38 patients received 1 ml
      saline placebo and lidocaine. The primary outcome measure was satisfaction with
      symptom relief. Thirty patients (70%) in the steroid-treated group were satisfied
      or highly satisfied compared with 13 (34%) of placebo-treated patients (P <
      0.001). Patients receiving steroids also showed significant improvement in median
      nerve conduction parameters and scores on validated symptom/function
      questionnaires. Forty-six patients were treated with serial injections for
      recurrent CTS symptoms. After 18 months, 17 patients reported adequate symptom
      relief with steroid injection, and 18 patients with unsatisfactory symptom relief
      were referred for carpal tunnel release surgery. We conclude that although
      steroid injections are safe and effective for temporary relief of CTS, most
      patients will eventually require surgery for long-term control of their symptoms.

PMID- 14694503
TI  - Electroneurography index based on nerve conduction study data: method and
      findings in control subjects.
AB  - We developed a summary score of data obtained from nerve conduction studies
      (NCS). The principle of such approach is that when a nonrandom trend to lower
      amplitudes or conduction velocities is present, it may be revealed by a summary
      nerve conduction score. In a group of normal subjects, peroneal, sural, ulnar,
      and superficial radial nerves were studied; age- and height-related F-wave and
      soleus H-reflex latencies were also examined. Z-scores of distal latencies,
      amplitudes, conduction velocities, F-wave latencies, and H-index were averaged in
      order to obtain three electroneurography (ENG) indices: a simple arithmetic (ENG
      index 1) and two weighted means (index 2 and index 3), assigning a double or
      triple weight to lower limb z-scores. Reference limits were established using
      multiple regression equations of ENG indices against age and height. This
      technique could be useful in providing a better cut-off between normal and
      diseased populations and in improving test-retest variability of NCS when follow
      up studies are required.

PMID- 14694504
TI  - Enhanced neuromuscular transmission efficacy in overloaded rat plantaris muscle.
AB  - To better understand the effect of muscle hypertrophy on the physiological
      properties of transmitter release, we investigated neuromuscular transmission
      (NMT) efficacy in overloaded rat plantaris muscle in situ. In the overload group,
      following bilateral tenotomy of plantaris synergists, rats were confined to wheel
      cages. Age-matched rats in the control group were confined to plastic cages.
      During the terminal experiment, muscle action potentials were blocked using micro
      conotoxin, and full-sized endplate potentials (EPPs) were recorded at 25, 50, and
      75 HZ to determine their amplitude rundown. Quantal contents for the control and
      overload groups were 37.0 and 74.3, respectively (P <0.01). There was a
      significant group difference in EPP amplitude rundown at all frequencies
      examined, with increased rundown occurring in the overload group (P < 0.01).
      Cumulative quantal release was 139% and 153% higher in the overload group at 25
      and 50 HZ, respectively (P < 0.05). Together, these data suggest the safety
      factor for NMT is increased by neuromuscular overload. Furthermore, these
      findings support and supplement previously reported activity-dependent
      improvements in NMT efficacy that are probably mediated via presynaptic
      adaptations.

PMID- 14694505
TI  - Effect of load during electrical stimulation training in spinal cord injury.
AB  - Electrical stimulation training is known to alter skeletal muscle characteristics
      after a spinal cord injury, but the effect of load on optimizing the training
      protocol has not been fully investigated. This study investigated two electrical
      stimulation training regimes with different loads on intramuscular parameters of
      the paralyzed lower limbs. Six paraplegic individuals with a spinal cord injury
      underwent electrical stimulation training (45 min daily for 3 days per week for
      10 weeks). One leg was trained statically with load, and the contralateral leg
      was trained dynamically with minimal load. Isometric force assessed with 35-HZ
      stimuli increased significantly in both legs from baseline, with the static
      trained leg also being significantly higher than the dynamic-trained leg. The
      vastus lateralis muscle of the statically trained leg showed a significant
      increase in type I fibers, fiber cross-sectional area, capillary-to-fiber ratio,
      and citrate synthase activity when compared to both baseline and the dynamically
      trained leg. Relative oxygenation of the vastus lateralis muscle as determined by
      near infrared spectroscopy was also significantly greater after static training.
      This study indicates that the load that is applied to paralyzed muscle during an
      electrical stimulation training program is an important factor in determining the
      amount of muscle adaptation that can be achieved.

PMID- 14694506
TI  - Assessment of voluntary activation by stimulation of one muscle or two
      synergistic muscles.
AB  - In order to test the hypothesis that suboptimal activation of synergistic muscles
      explains the nonlinear nature of the interpolated twitch-voluntary torque
      relationship, we evaluated differences between stimulating a single muscle
      [biceps brachii (BB)] and two synergists simultaneously [BB and brachioradialis
      (BR)] on variables related to the estimation of voluntary activation. Ten
      subjects performed maximal and submaximal voluntary contractions while electrical
      stimulation was applied either to the BB, or BB and BR simultaneously, to assess
      voluntary activation. Simultaneous stimulation of the two synergistic muscles
      produced significantly greater torque at rest and a significantly greater
      activation index (95% vs. 91.7% for stimulation of BB only). However,
      simultaneous stimulation of BB and BR did not consistently elicit greater
      additional torque during contraction, nor did it improve the linearity of the
      interpolated twitch-voluntary torque relationship. The greater activation index
      observed for the simultaneous stimulation of BB and BR compared to BB is
      explained by the greater torque elicited at rest. We conclude that the nonlinear
      relationship between interpolated and voluntary elbow flexion torque is not
      explained by suboptimally activated synergistic muscles.

PMID- 14694507
TI  - Satellite cells and myonuclei in young and elderly women and men.
AB  - The overall aim of this study was to assess the effects of aging on the satellite
      cell population. Muscle biopsies were taken from the tibialis anterior muscle of
      healthy, moderately active young (age range, 20-32 years; n = 31) and elderly
      (age range, 70-83 years; n = 27) women and men with comparable physical activity
      pattern. Satellite cells and myonuclei were visualized using a monoclonal
      antibody against neural cell adhesion molecule and counterstained with Mayer's
      hematoxylin. An average of 211 (range, 192-241) muscle fibers were examined for
      each individual. Compared with the young women and men, the elderly subjects had
      a significantly lower (P < 0.011) number of satellite cells per muscle fiber but
      a significantly higher (P < 0.004) number of myonuclei per muscle fiber. The
      number of satellite cells relative to the total number of nuclei [satellite
      cells/(myonuclei + satellite cells)] was significantly lower in the elderly than
      in the young women and men. These results imply that a reduction in the satellite
      cell population occurs as a result of increasing age in healthy men and women.

PMID- 14694508
TI  - Direct measurement of human sympathetic nerve conduction velocity.
AB  - We evaluated a method for direct measurement of conduction velocity (CV) in
      sympathetic nerves in humans using a double-recording method of skin sympathetic
      nerve activity (SSNA) by microneurography. SSNA in the tibial nerve was recorded
      simultaneously at proximal and distal sites in the popliteal fossa (short
      distance study) or at the popliteal fossa and ankle (long-distance study). In
      both studies, CVs were determined by dividing the interelectrode distance on the
      skin by the difference in conduction time between the rising-phases (rising-phase
      analysis) or peaks of the integrated bursts (peak-to-peak analysis). The
      measurement using long distance and peak-to-peak analysis had the highest
      accuracy; it is an orthodromic conduction measurement, is unrelated to eliciting
      stimulus, has high temporal resolution, and is not affected by the effector organ
      conditions. The average CV of resting SSNA was 0.93 +/- 0.09 m/s.

PMID- 14694509
TI  - Isolated sensory manifestations in neuralgic amyotrophy: report of eight cases.
AB  - A series of eight patients with isolated clinical and electrophysiological
      sensory deficit related to neuralgic amyotrophy (NA) is reported. NA was
      diagnosed by clinical and electrodiagnostic features and disease course. Imaging
      and laboratory investigations excluded other disorders. The results showed mild
      to severe involvement of eight individual sensory nerves: lateral antebrachial
      cutaneous nerve lesions in three instances and partial lesions of the median
      nerve in five cases. Our findings suggest that isolated clinical and
      electrodiagnostic sensory involvement in NA is not exceptional but rather is
      unrecognized. The pattern of these nerve lesions agrees with the most typical
      pattern of NA, which is a mononeuritis or mononeuritis multiplex. The present
      study also shows that the spectrum of NA is diverse and may vary from pure motor
      to pure sensory deficit, according to the nature of the involved nerve fibers.

PMID- 14694510
TI  - Evoked potentials elicited by stimulation of the lateral and anterior femoral
      cutaneous nerves in meralgia paresthetica.
AB  - Seventy-five consecutive patients with clinical symptoms and signs of meralgia
      paresthetica underwent bilateral somatosensory evoked potential (SEP) studies
      involving stimulation of skin areas innervated by the lateral and anterior
      femoral cutaneous nerves of the thighs. The most common abnormality was an
      absolute lateral femoral cutaneous SEP latency > 40 ms in 35 patients (47%),
      followed by an absent response in 14 patients (19%), an absolute latency < 40 ms
      but amplitude reduction > 50% compared with the contralateral response in 8
      patients (11%), and an absolute latency < 40 ms but > 5 ms interside latency
      difference in 5 patients (7%). Anterior femoral cutaneous SEPs were of value in
      distinguishing meralgia paresthetica from a proximal lumbar radiculopathy in an
      additional 4 patients and confirming bilateral meralgia paresthetica in 10
      patients.

PMID- 14694511
TI  - Acquired rippling muscle disease with myasthenia gravis.
AB  - Rippling muscle disease (RMD) is a rare disorder that occurs in both familial and
      sporadic forms. Seven patients have previously been reported with myasthenia
      gravis and sporadic RMD. There have been conflicting reports of the
      electrophysiological characteristics of rippling muscles in this acquired form.
      Another such patient is reported, and the clinical, electrophysiological, and
      laboratory features of this disorder are described. In addition, this patient had
      alopecia areata and recurrent metastatic thymoma, years after resection of a
      benign thymoma. This report emphasizes the clinical manifestations of RMD in
      association with myasthenia gravis (RMD-MG), and its distinctive features, in
      this and previously reported patients.

PMID- 14694512
TI  - Bilateral neurogenic thoracic outlet syndrome.
AB  - We report a case of bilateral neurogenic thoracic outlet syndrome (TOS).
      Electrophysiological examination suggested the presence of bilateral lower
      brachial plexus neuropathy. Radiography showed rudimentary bilateral cervical
      ribs. In the cases reported in the literature to date, the clinical findings are
      typically unilateral despite the common presence of bilateral bony abnormalities.
      Neurogenic TOS should be considered in young women, even if they present with
      bilateral symptoms, when they have occupations requiring strenuous activity of
      the upper limbs.

PMID- 14694513
TI  - Sphincter electromyography in diagnosis of multiple system atrophy: technical
      issues.
AB  - Possible technical reasons for the controversy over the role of sphincter
      electromyography (EMG) in the diagnosis of multiple system atrophy (MSA) were
      analyzed. In a review of the literature, a high sensitivity (>60%) was found
      reported in 11 studies that included late components, and no value of the test
      was found in 4 studies that excluded them. This was also corroborated in a pilot
      study of 5 patients with probable MSA. With late components included, the mean
      motor unit potential (MUP) duration was prolonged in all 4 patients with an
      adequate single-MUP analysis sample and, with late components excluded, in 2 of 5
      patients on multi-MUP analysis. At least in diagnostic EMG of MSA patients, late
      components should be included in the measurement of MUP duration.

PMID- 14694515
TI  - Human papillomavirus integration: detection by in situ hybridization and
      potential clinical application.
AB  - Human papillomaviruses (HPVs) are accepted as a necessary cause of cervical
      neoplasia. However, the benefits of testing simply for high-risk HPV types are
      limited because of their high prevalence in intraepithelial lesions of all
      grades, the majority of which regress if left untreated. One factor considered to
      be of key importance for the progression of intraepithelial lesions to invasive
      disease is integration of HPV into the host cell genome. Although questions
      remain about the prevalence of integration amongst pre-invasive lesions,
      sensitive in situ hybridization techniques utilizing tyramide reagents may aid
      determination of the significance of HPV infection by enabling routine detection
      of both high-risk HPV and its physical status. This will provide important data
      relevant not only to our understanding of the biology of HPV-associated
      neoplasia, but also potentially to clinical testing for HPV.

PMID- 14694516
TI  - Are tumours angiogenesis-dependent?
AB  - The final proof of principle that cancer patients can be effectively treated with
      angiogenesis inhibitors is eagerly awaited. Various preclinical in vivo
      experiments have proven that most tumours need new vessel formation in order to
      grow and to form metastases. First of all, tumours do not grow in avascular
      corneas until new blood vessels reach the implant. Secondly, the introduction of
      only one angiogenic gene can cause a switch from tumour dormancy to progressive
      tumour growth. Thirdly, tumour growth can be inhibited and sometimes tumour
      regression can be obtained just by attacking the vascular compartment with
      specific angiogenesis inhibitors. These three examples of preclinical experiments
      and many others have led to the conclusion that, in general, tumours are
      angiogenesis-dependent. Supported by disappointing clinical results, the
      angiogenesis dependency of tumours has been questioned, mainly because of the
      immaturity and the presumed lack of a functional blood supply (oxygen delivery
      and discarding of waste products) from a newly formed tumour vasculature.
      However, human tumours are highly heterogeneous in vascular architecture,
      differentiation, and functional blood supply. Vascular immaturity is a natural
      consequence of a genetically based unlimited expansion of tumour cells, compared
      to the well-regulated growth of different organs during embryonic development,
      for example. Unlimited tumour expansion and therefore the continuous stimulation
      of vessel outgrowth prevent endothelial cells from generating a mature
      vasculature, but instead continuously stimulate them to expand the vascular
      compartment of the growing tumour. In this review, the translation of
      angiogenesis inhibitors as a treatment for cancer from preclinical experiments to
      the clinic is evaluated. The preclinical evidence that tumours are angiogenesis
      dependent is summarized and explanations are put forward for why the clinical
      results so far are not as exciting as was expected from preclinical studies.
      Reviewing the translation, one may conclude that human tumours are heterogeneous
      in their vascular architecture and function and that tumour-induced angiogenesis
      in humans is a more complex (multifactorially regulated) process compared with
      angiogenesis in preclinical cancer models.

PMID- 14694517
TI  - Differential expression of matrilysin-1 (MMP-7), 92 kD gelatinase (MMP-9), and
      metalloelastase (MMP-12) in oral verrucous and squamous cell cancer.
AB  - Squamous cell carcinoma (SCC) of the oral cavity is a highly invasive tumour of
      stratified squamous epithelium that spreads through degradation of the basement
      membrane (BM) and extracellular matrix (ECM). There are currently no reliable
      tissue or serum markers to predict whether the tumour has metastasized at the
      time of diagnosis. Verrucous carcinoma (VC) of the oral cavity is a rare low
      grade variant of oral SCC that penetrates into the subepithelial connective
      tissue. Many matrix metalloproteinases (MMPs), such as MMP-1, -2, -7, -9, -13,
      and -14, as well as integrin receptors have been implicated in cancer invasion.
      Integrin alphavbeta6 is induced in SCC and appears to be involved in up
      regulation of MMP-9 expression by oral keratinocytes and promotion of their
      migration. The aim of this study was to investigate whether the pattern of MMP
      expression or that of alphavbeta6 integrin contributes to the differences in the
      biological behaviour of oral SCC and VC. The results show that the less
      aggressive nature of oral VC may be connected to its MMP expression profile.
      Typically, VCs were devoid of epithelial MMP-3, -7, -9, -12 and -13 expression,
      compared with SCCs. MMP-19 was expressed by epithelial keratinocytes in
      hyperproliferative areas of verrucous hyperplasia, VC, and SCC, but was absent in
      the invasive cancer cell nests of SCC. MMP-26 was expressed by hyperproliferative
      keratinocytes in VC as well as by invasive cancer cells in SCCs. MMP-10 was
      expressed widely in the epithelium of all SCC specimens. alphavbeta6 integrin
      expression was also detected in some cases of epithelial hyperplasia but was
      significantly more abundant in cancers at the invasive front. The absence of MMP
      7, -9 and -12 from epithelial cells may serve as a good prognostic marker of non
      invasive oral carcinoma. Blocking the activity of invasion-specific MMPs or
      alphavbeta6 integrin might offer novel therapeutic modalities in early-stage oral
      carcinoma.

PMID- 14694518
TI  - Transition of high-grade cervical intraepithelial neoplasia to micro-invasive
      carcinoma is characterized by integration of HPV 16/18 and numerical chromosome
      abnormalities.
AB  - Cervical intraepithelial neoplasia (CIN I, II, and III) and cases of CIN III
      associated with micro-invasive cervical carcinoma (CIN III & mCA) were analysed
      for evidence of episomal or integrated human papillomavirus (HPV) 16/18 DNA by
      fluorescence in situ hybridization (FISH). In parallel, numerical aberrations of
      chromosomes 1, 17, and X were determined in these lesions as indicators of
      genomic instability. HPV 16/18 DNA was present in 2 of 12 CIN I, 19 of 23 CIN
      II/III, and 10 of 12 CIN III & mCA. None of the CIN I and only two of the 19 HPV
      16/18-positive solitary CIN II/III showed an integrated HPV pattern. However, all
      ten cases of HPV-positive CIN III & mCA showed this pattern. Transition of CIN
      II/III to CIN III & mCA therefore correlates strongly with viral integration
      (p<0.001). Chromosomal aberrations were detected in 23 of 31 HPV 16/18-positive
      lesions (14 solitary CIN I-III and nine CIN III & mCA) and 5 of 16 HPV-negative
      lesions. Nine of 21 HPV 16/18-positive solitary CIN I-III showed tetrasomy for
      all chromosomes tested, while trisomies for a single chromosome were seen in a
      further five of these HPV-positive lesions. In eight of ten HPV-positive CIN III
      & mCA, predominantly aneusomies and/or polysomies were detected. A significant
      correlation (p<0.02) was found between the chromosome copy number and the
      physical status of HPV, indicating that in its episomal form HPV induces genomic
      changes such as tetrasomies and single trisomies, while HPV integration
      correlates with aneusomies and polysomies, predominantly detected in CIN III &
      mCA. These data indicate that integration of HPV 16/18 DNA is a pivotal step in
      the transition of CIN to micro-invasive carcinoma.

PMID- 14694519
TI  - Expression of interleukin-6 and monocyte chemoattractant protein-1 by peritoneal
      sub-mesothelial cells during abdominal operations.
AB  - Cytokines and chemokines including interleukin-6 (IL-6) and monocyte
      chemoattractant protein-1 (MCP-1) are secreted in response to major abdominal
      operations. The aim of this study was to identify the peritoneal cells that
      produce IL-6 and MCP-1. Samples of peritoneal tissue were taken from patients at
      the beginning and end of major abdominal operations. The samples were incubated
      in culture medium on microtitre plates for 5 h. The concentrations of IL-6 and
      MCP-1 were measured in culture supernatants by enzyme-linked immunosorbent assay
      (ELISA). In paraffin sections, cells that expressed IL-6 or MCP-1 were identified
      by combined in situ hybridization and immunohistochemistry. Antibodies against
      CD68, CD34, actin, and calretinin were included in these experiments. The median
      production of IL-6 increased significantly from 6256 pg/ml at the start of the
      operation to 20,000 pg/ml at the end. Production of MCP-1 rose from 7700 pg/ml to
      11,820 pg/ml. IL-6 mRNA was mainly confined to endothelial cells. MCP-1 was
      expressed by a broader range of cells, consisting of actin-positive smooth muscle
      cells and endothelial cells, fibroblast-like cells, as well as occasional
      macrophages and mesothelial cells. Peritoneal endothelial cells contribute to the
      transient increase in concentrations of IL-6 in the circulation after surgical
      trauma. Recruitment of monocytes to the site of the trauma seems to be mainly
      effected by actin-positive smooth muscle cells and endothelial cells.

PMID- 14694520
TI  - Immunohistochemical analysis of the IL-6 family of cytokines and their receptors
      in benign, hyperplasic, and malignant human prostate.
AB  - Interleukin-6 (IL-6) and its receptor have been implicated in prostate cancer
      progression. Because other members of the IL-6 family such as leukaemia
      inhibitory factor (LIF) and oncostatin M (OSM) share gp130, the signal
      transduction subunit of their receptors, interpretation of the data without
      considering the expression of these cytokines and their specific receptor
      subunits could be misleading. The immunohistochemical pattern of the IL-6 family
      and their receptor subunits in normal prostate, benign prostatic hyperplasia
      (BPH), and prostatic carcinoma (PC) was investigated. In normal prostates, gp130
      and OSMRalpha were detected exclusively in the stroma and LIFRbeta was very
      scarce. While IL-6 was scarcely immunolocalized to the basal cells of the
      epithelium, OSM was detected in the stroma and LIF in both the epithelium and the
      stroma. This suggests an autocrine role for this family of cytokines in the
      stroma of normal prostates. In BPH, gp130 and OSMRalpha were detected both in the
      epithelium and in the stroma, whereas LIFRbeta was localized only to the
      epithelium. IL-6 localized preferentially to the epithelium, OSM to the stroma,
      and LIF to both compartments. Therefore, in addition to the autocrine role in the
      stroma, IL-6 and OSM may play a paracrine role from the stroma to the epithelium
      in BPH. In PC, gp130 and OSMRalpha were detected both in the epithelium and in
      the stroma, increasing with rising Gleason grade, whereas LIFRbeta was localized
      exclusively to the epithelium of low Gleason grade carcinomas. IL-6, LIF, and OSM
      localized in all cell types, with immunostaining increasing with Gleason grade.
      These data suggest an autocrine role for these cytokines in the epithelial cells
      of PC. The distinct pattern of expression of LIFRbeta exclusively in low Gleason
      grade carcinomas makes LIFRbeta a candidate for malignancy diagnosis. The role of
      OSM mainly in high Gleason grade carcinomas makes OSM a putative target for
      prostate cancer therapy.

PMID- 14694521
TI  - Blockade of the type I IGF receptor expression in human prostate cancer cells
      inhibits proliferation and invasion, up-regulates IGF binding protein-3, and
      suppresses MMP-2 expression.
AB  - The type I insulin-like growth factor receptor (IGF-IR) is involved in tumour
      cell proliferation, invasion, and cancer cell survival. Several studies indicate
      that the IGF axis contributes to prostate cancer pathogenesis, but there is no
      consensus regarding the relative expression of the IGF-IR in benign and malignant
      prostate epithelium. In this study, endogenous IGF-IR gene expression was reduced
      in stably transfected PC-3 cells by employing an antisense RNA strategy which
      resulted in significant suppression of both PC-3 cell invasion and proliferation
      in vitro. Furthermore, it was demonstrated that a direct correlation exists
      between the inhibition of IGF-IR gene expression and either up-regulation of IGF
      binding protein (BP)-3 or down-regulation of matrix metalloproteinase (MMP)-2
      expression in androgen-independent PC-3 cells. Moreover, inhibition of IGF-IR
      gene expression in transfected PC-3 cells leads to an enhanced rate of
      spontaneous apoptosis. In addition, expression analyses by quantitative RT-PCR on
      RNA from laser microdissected matched normal prostate and prostate tumour samples
      revealed that IGF-IR gene expression was up-regulated in nine of 12 prostate
      cancers, whereas IGFBP-3 gene expression was down-regulated in all 12 prostate
      carcinomas analysed. These results indicate an important role for IGF-IR and
      IGFBP-3 in the homeostasis of prostate carcinoma cells and provide a further
      basis for targeting IGF-IR or IGFBP-3 gene expression in order to improve
      understanding of the IGF-IR-activated signalling pathways and as a potential
      treatment for prostate cancer.

PMID- 14694522
TI  - Differential Emu enhancer activity and expression of BOB.1/OBF.1, Oct2, PU.1, and
      immunoglobulin in reactive B-cell populations, B-cell non-Hodgkin lymphomas, and
      Hodgkin lymphomas.
AB  - It has previously been demonstrated that in cultured and in situ tumour cells of
      classical Hodgkin lymphoma (cHL), the immunoglobulin (Ig) promoter is inactive
      and its transcription factors Oct2 and/or BOB.1/OBF.1 are down-regulated. In this
      study, the analysis of these transcription factors has been extended to a broad
      spectrum of B-cell malignancies and the findings have been related to the
      situation in normal B-cells of various differentiation stages and to the
      expression of Ig. Furthermore, an additional Ig transcription factor, PU.1,
      recently described to be absent from cHL, and a further regulatory element of the
      Ig gene, the intronic Emu enhancer, have been studied. BOB.1/OBF.1 and Oct2 were
      present in all B-cells expressing Ig, whereas PU.1 proved to be absent from late
      B-cell differentiation stages and from a subset of germinal centre B-cells.
      Interestingly, there were several normal (eg germinal centre centroblasts and
      monocytoid B-cells) and malignant B-cell populations (eg a proportion of diffuse
      large B-cell lymphomas, DLBCLs) that were Ig-negative, despite their BOB.1/OBF.1
      and Oct2 expression. This study further shows that absence of PU.1 alone, as well
      as inactivation of the intronic Emu enhancer, is not sufficient to down-regulate
      Ig transcription. Taken together, the simultaneous absence of PU.1, Oct2, and/or
      BOB.1/OBF.1 is unique to Hodgkin and Reed-Sternberg (HRS) cells and cannot be
      detected in normal B-cell subsets or B-cell non-Hodgkin lymphomas (B-NHLs). This
      supports the concept that the down-regulation of Ig in cHL does not reflect a
      physiological situation, but a defect probably closely linked to the pathogenesis
      of cHL.

PMID- 14694523
TI  - Presence and localization of T-cell subsets in relation to melanocyte
      differentiation antigen expression and tumour regression as assessed by
      immunohistochemistry and molecular analysis of microdissected T cells.
AB  - Melanoma-associated antigens may be the driving force behind the lymphocytic
      infiltrates in melanomas and the occurrence of melanoma regression. To
      investigate the clinical relevance of melanoma differentiation antigens (MDAs) as
      T-cell targets, the relationship between the presence and localization of T-cell
      subsets and the expression of MDAs was studied by immunohistochemistry and the
      diversity of CD8+ T cells in regressive melanomas was assessed using laser
      assisted microdissection. While MDA expression as well as T-cell subset
      distribution, as assessed by immunohistochemical analysis, was heterogeneous
      within and between lesions, they were histologically independent phenomena. In
      four lesions studied in detail by PCR analysis of microdissected T cells, a
      limited T-cell diversity and evidence for clonally expanded tumour infiltrating
      lymphocytes were found. However, no major differences in T-cell diversity, as
      assessed by PCR analysis, between peri-and intra-tumoural areas became apparent,
      this despite the known clinical significance of the specific localization of a T
      cell infiltrate. T cells of clonal origin did not show preferential localization
      to regressive tumour areas. Moreover, clonally related cells were found in two
      lesions with a non-brisk infiltrate, while in two lesions with a brisk infiltrate
      (clinically, a good prognostic factor) no evidence for clonally expanded tumour
      infiltrating lymphocytes was found. These data support the notion that specific
      immune reactivity and homing of specific cells to the tumour can occur in
      melanoma patients. However, they also show that the presence of clonally expanded
      T cells in the tumour is not necessarily associated with an effective anti-tumour
      immune response and may, for instance, represent regulatory cells. It appears
      that the clinical impact of an anti-tumour immune response is largely decided at
      the tumour site, where micro-environmental conditions dictate the functional
      state of the T cells. Full understanding of these processes can only be achieved
      by performing more dynamic analyses of the local host-tumour interactions.

PMID- 14694524
TI  - Absence of c-kit gene mutations in gastrointestinal stromal tumours from
      neurofibromatosis type 1 patients.
AB  - Most sporadic gastrointestinal stromal tumours (GISTs) have somatic c-kit gene
      mutations that are considered to be causal. Neurofibromatosis type 1 (NF1) is
      caused by mutations of the NF1 gene and NF1 patients have an increased risk of
      developing GISTs. Since most neoplasms are considered to develop as a result of
      the combination of several gene mutations, these findings suggest that GISTs from
      NF1 patients might have somatic c-kit gene mutations and that sporadic GISTs from
      non-NF1 patients might have somatic NF1 gene mutations. The present study
      analysed 29 GISTs from seven NF1 patients for c-kit gene mutations and ten
      sporadic GISTs from ten non-NF1 patients for NF1 mutations. Exons 9, 11, 13, and
      17 of the c-kit gene were amplified and directly sequenced after the extraction
      of genomic DNA from wax-embedded tissues from 26 GISTs from five NF1 patients.
      The whole coding region of the c-kit cDNA and the whole coding region of the NF1
      cDNA were amplified and directly sequenced after RNA extraction and cDNA
      synthesis in three fresh GIST tissues from two NF1 patients and ten fresh GIST
      tissues from ten non-NF1 patients. Of the ten sporadic GISTs, eight had
      heterozygous mutations at exon 11, and one at exon 9, of c-kit. Heterozygous NF1
      gene mutations were detected in GISTs from the two NF1 patients from whom fresh
      tissues were available. None of the 29 GISTs derived from NF1 patients had
      detectable c-kit gene mutations and none of the ten GISTs derived from non-NF1
      patients had detectable NF1 mutations. These results suggest that the
      pathogenesis of GISTs in NF1 patients is different from that in non-NF1 patients.

PMID- 14694525
TI  - Differential expression of the calcium sensing receptor and combined loss of
      chromosomes 1q and 11q in parathyroid carcinoma.
AB  - Malignant transformation of parathyroid tumours is rare. Nevertheless, this small
      subset of malignant tumours often creates diagnostic and therapeutic problems. In
      this work, the morphological characteristics of 26 primary parathyroid carcinomas
      and seven metastases have been studied. Furthermore, immunohistochemical
      expression profiles for the calcium sensing receptor (CASR), cyclin D1 (CCND1),
      and Ki-67 were determined for parathyroid carcinomas and compared with adenomas
      and hyperplasias using a tissue microarray. Loss of heterozygosity (LOH) of the
      chromosome 1q region containing the HRPT2 gene and chromosome 11q (MEN1) was
      determined in the carcinomas. In contrast to the adenomas and hyperplasias, 31%
      of carcinomas demonstrated down-regulation of CASR. A significant correlation was
      found between CASR expression and the Ki-67 proliferation index. Chromosome 1q
      and chromosome 11q LOH were found in 12 of 22 (55%) and 11 of 22 (50%) carcinomas
      tested, respectively. Combined 1q and 11q LOH was seen in 8 of 22 (36%)
      carcinomas, in contrast to the low percentage of LOH reported in both regions in
      adenomas. In conclusion, this study demonstrates that combined 1q and 11q LOH in
      parathyroid tumours is suggestive of malignant behaviour. Strong down-regulation
      of the CASR protein is seen in a proportion of parathyroid carcinomas with a high
      proliferation index.

PMID- 14694526
TI  - Evaluation of MDM2 and CDK4 amplification by real-time PCR on paraffin wax
      embedded material: a potential tool for the diagnosis of atypical lipomatous
      tumours/well-differentiated liposarcomas.
AB  - Atypical lipomatous tumours/well-differentiated liposarcomas and dedifferentiated
      liposarcomas are characterized by 12q13-15 region amplification. In contrast,
      this molecular event has not been reported in benign lipomas. Within the 12q13-15
      chromosomal region, the MDM2, SAS, HMGA2, and CDK4 genes are the most frequent
      targets of amplification. A series of lipomas (36 cases) and liposarcomas (48
      cases) was analysed for MDM2 and CDK4 gene amplification by real-time PCR. MDM2
      and CDK4 gene amplification was detected in 2.8% and 5.6% of lipomas and 98.2%
      and 82.4% of liposarcomas, respectively. Moreover, co-amplification of the two
      genes as well as a higher-level amplification was observed more frequently in
      dedifferentiated liposarcomas than in atypical lipomatous tumours/well
      differentiated liposarcomas. Real-time PCR proved to be a fast and reliable
      method to characterize lipomas and liposarcomas by quantification of MDM2 and
      CDK4 gene amplification. It is applicable to paraffin wax-embedded tissues and
      could be useful when histological diagnosis is difficult.

PMID- 14694527
TI  - Fibroblast growth factor 2 induces differentiation and apoptosis of Askin tumour
      cells.
AB  - Peripheral primitive neuroectodermal tumour (PNET)/Ewing's sarcoma (ES) and
      neuroblastoma (NB) are related tumours of neural crest origin with primitive
      neural characteristics. Fibroblast growth factor 2 (FGF2) is a critical
      signalling molecule for primitive neural crest cells. The treatment of NB cells
      with FGF2 variably affects biological characteristics such as growth and
      differentiation, while in PNET/ES, FGF2 predominantly induces apoptosis. The JK
      GMS Askin tumour cell line can be induced to differentiate upon treatment with
      nerve growth factor (NGF), indicating the integrity of the cellular machinery
      necessary for differentiation. The present study assesses whether FGF2 can induce
      differentiation in JK-GMS cells. JK-GMS cells expressed high-affinity FGF
      receptors (FGFRs), and treatment with FGF2 induced phosphorylation of FGFR1
      together with activation of extracellular signal-regulated kinases (ERK1/ERK2)
      and c-Jun N-terminal kinase (JNK). Subsequent biological effects were growth
      inhibition, neuronal differentiation, and apoptosis, and these changes were
      associated with increased expression of neurofilaments, reduction of c-myc and
      bcl-2 expression, and activation of caspase 3. Treatment of the cells with a
      specific inhibitor of the MAPK/extracellular signal-regulated kinase (MEK)-1,
      PD98059, predominantly inhibited the effects of FGF2 on growth, differentiation,
      and apoptosis, while an inhibitor of JNK reduced apoptosis, indicating that the
      ERK1/2 and JNK pathways are critical components of FGF2-mediated effects in JK
      GMS cells. Additional comparative analyses of FGF2-mediated effects in two ES
      cell lines (CADO-ES, RD-ES) and a PNET cell line (SK-N-MC) showed pronounced
      differentiation in SK-N-MC, but not in CADO-ES or RD-ES cells. This study
      demonstrates that FGF2 can induce neuronal differentiation of PNET including
      Askin tumour. These findings clearly indicate that the FGF2-mediated signalling
      pathway plays a critical role in controlling the major properties of PNET cells
      and may provide a potential therapeutic target for PNET.

PMID- 14694528
TI  - Expression of cartilage growth plate signalling molecules in chondroblastoma.
AB  - Chondroblastoma (CB) is a rare benign tumour (<1% of all bone tumours) involving
      epiphyseal long bones (male:female 1.5:1). During development, and in the
      postnatal period, IHh/PTHrP and FGF signalling molecules control the space and
      timing of chondrocyte differentiation. Considering the close relationship of CB
      with the growth plate (age and location), the expression of proteins involved in
      epiphyseal growth regulation was studied. Twelve cases of CB were retrieved.
      Immunohistochemistry was performed using antibodies against fibroblast growth
      factor-2 (FGF-2), fibroblast growth factor receptor-1 (FGFR-1), FGFR-3, bcl-2,
      p21, parathyroid hormone-related peptide (PTHrP), and parathyroid hormone-related
      peptide receptor (PTHR1). Three observers evaluated haematoxylin and eosin (H&E)
      stained and immunostained slides independently. Semi-quantitative estimation of
      the matrix, the type of matrix, and immunostaining was performed. Cellular and
      matrix-rich areas were evaluated separately. Diverse amounts and types of matrix
      were present in different tumours, as well as within individual tumours.
      Signalling molecules were expressed in 50-100% of the cases. Higher levels of
      expression were found in cellular areas than in matrix-rich areas, especially for
      PTHR1, bcl-2, and FGFR-3. CB is an unusual entity affecting specific sites,
      showing that both IHh/PTHrP and FGF signalling are active. Higher expression was
      found in cellular than in matrix-rich areas, as in the proliferating/pre
      hypertrophic growth plate zone in comparison with the hypertrophic/calcifying
      zone. Previous studies have shown the same molecules to be expressed with a
      similar pattern in chondrosarcomas. The sum of the evaluated features indicates
      that CB is a neoplasm originating from a mesenchymal cell committed towards
      chondrogenesis via active growth plate signalling pathways.

PMID- 14694529
TI  - Hypertrophic scar formation is associated with an increased number of epidermal
      Langerhans cells.
AB  - The exact pathogenesis of hypertrophic scar and keloid formation is still unknown
      and a good therapy to prevent or treat these scars is lacking. Because
      immunological processes seem to be important in excessive scar formation,
      immunological cells and parameters were studied in a standardized breast
      reduction wound-healing model in the present study. Standardized scar samples
      were taken from infra-mammary breast reduction scars, 3 and 12 months following
      surgery. The samples were investigated for their number of mast cells, Langerhans
      cells, T-lymphocytes, and macrophages, and the presence of interleukin-4 (IL-4)
      and counter-regulating interferon-gamma (gamma-IFN), in relation to the scar's
      clinical appearance--normal or hypertrophic. In this study, hypertrophic scar
      formation was significantly associated with an increased number of epidermal
      Langerhans cells (p=0.0001) and significantly (p<0.05) increased expression of
      epidermal IL-4. No relationship was found between mast cell, T-lymphocyte and
      macrophage numbers or gamma-IFN staining and the formation of normal or
      hypertrophic scars. These results, combined with previous observation of abnormal
      keratinocyte behaviour in this context, indicate that the epidermal immune
      barrier plays an important role in the development of hypertrophic scars.

PMID- 14694530
TI  - A fluid cover medium provides superior morphology and preserves RNA integrity in
      tissue sections for laser microdissection and pressure catapulting.
AB  - Laser microdissection and pressure catapulting has become a powerful tool to
      obtain homogeneous cell populations from tissue samples in nearly all fields of
      biomedical research. The isolated cells can be subsequently used for the analysis
      of proteins, DNA or RNA. However, the method requires physical access to the
      tissue surface and the sections therefore need to be air-dried and uncovered. The
      consequence is poor morphology, which severely reduces the potential of the
      technique, especially in non-homogeneous tissues or tissues with infiltrating
      immune cells. To overcome this limitation, a fluid cover medium was developed and
      the effects on frozen and paraffin wax-embedded tissue morphology were evaluated.
      The cover medium improved the morphology such that it was almost comparable to
      sections overlaid with glass coverslips. Moreover, the laser microdissection
      procedure was facilitated, since the medium allowed larger areas of tissues to be
      laser pressure-catapulted. Neither the isolation of proteins nor the extraction
      of genomic DNA was adversely affected by the use of the fluid cover medium. No
      significant differences in RNA quantity and integrity were detected by TaqMan
      real-time PCR for GAPDH, and microchip electrophoresis, between covered and
      uncovered tissue sections. In conclusion, this method provides considerably
      improved morphology for laser microdissection and pressure catapulting techniques
      without affecting RNA-dependent downstream applications. This not only
      facilitates established procedures, but will also extend the application to
      tissues that require superior morphological resolution.

PMID- 14694531
TI  - Actions of a histaminergic/peptidergic projection neuron on rhythmic motor
      patterns in the stomatogastric nervous system of the crab Cancer borealis.
AB  - Histamine is a neurotransmitter with actions throughout the nervous system of
      vertebrates and invertebrates. Nevertheless, the actions of only a few identified
      histamine-containing neurons have been characterized. Here, we present the
      actions of a histaminergic projection neuron on the rhythmically active pyloric
      and gastric mill circuits within the stomatogastric ganglion (STG) of the crab
      Cancer borealis. An antiserum generated against histamine labeled profiles
      throughout the C. borealis stomatogastric nervous system. Labeling occurred in
      several somata and neuropil within the paired commissural ganglia as well as in
      neuropil within the STG and at the junction of the superior oesophageal and
      stomatogastric nerves. The source of all histamine-like immunolabeling in the STG
      neuropil was one pair of neuronal somata, the previously identified inferior
      ventricular (IV) neurons, located in the supraoesophageal ganglion. These neurons
      also exhibited FLRFamide-like immunoreactivity. Activation of the IV neurons in
      the crab inhibited some pyloric and gastric mill neurons and, with inputs from
      the commissural ganglia eliminated, terminated both rhythms. Focal application of
      histamine had comparable effects. The actions of both applied histamine and IV
      neuron stimulation were blocked, reversibly, by the histamine type-2 receptor
      antagonist cimetidine. With the commissural ganglia connected to the STG, IV
      neuron stimulation elicited a longer-latency activation of commissural projection
      neurons which in turn modified the pyloric rhythm and activated the gastric mill
      rhythm. These results support the hypothesis that the histaminergic/peptidergic
      IV neurons are projection neurons with direct and indirect actions on the STG
      circuits of the crab C. borealis.

PMID- 14694532
TI  - GABAergic projection from the ventral tegmental area and substantia nigra to the
      periaqueductal gray region and the dorsal raphe nucleus.
AB  - Previous studies have shown that neurons in the ventral tegmental area (VTA) and
      substantia nigra (SN) project to the ventrolateral periaqueductal gray (PAGvl)
      and dorsal raphe nucleus (DR). Research has also shown that stimulation of
      neurons in the VTA/SN elicits cardiovascular depressor responses that are
      mediated by a projection to the PAGvl/DR. Anatomic and physiological experiments
      were done in the present study to determine the neurochemical identity of the
      VTA/SN projection to the PAGvl/DR. Experiments were done to characterize the
      origin and chemical nature of this projection by combining cholera toxin B
      tracing with immunofluorescence for the 67K isoform of glutamic acid
      decarboxylase (GAD) and tyrosine hydroxylase. The PAGvl/DR region was found to
      receive a substantial input from neurons in the VTA, SN, and deep mesencephalic
      nucleus. The DR was preferentially innervated by neurons in the VTA, whereas the
      PAGvl was preferentially innervated by neurons in the SN. A proportion of neurons
      in the VTA and the reticular portion of the SN found to project to the PAGvl/DR
      were GAD positive. In addition, experiments were done in urethane-anesthetized
      rats to determine whether injections of a gamma-aminobutyric acid (GABA)
      antagonist in the region of the PAGvl/DR attenuated the cardiovascular depressor
      responses produced by glutamate stimulation of the VTA/SN. Injections of the GABA
      blocking agent picrotoxin (2.5 nmol, 500 nl) into the PAGvl/DR eliminated the
      cardiovascular responses from stimulation of the VTA/SN (0.01 M, 50 nl). The
      results of the present investigation provide evidence for a GABAergic projection
      from the VTA/SN to the PAGvl/DR. This projection may be an important regulator of
      the PAGvl/DR, an area of the midbrain involved in the production of behavioral
      and physiological responses to pain and stress.

PMID- 14694533
TI  - Subcellular distribution of spinophilin immunolabeling in primate prefrontal
      cortex: localization to and within dendritic spines.
AB  - Signal transduction in the nervous system depends on kinases and phosphatases,
      whose localization is regulated by a large group of scaffolding proteins. In
      particular, protein phosphatase-1 mediates dopamine's actions on a variety of
      substrates, including glutamate receptors, and this, in turn, depends on the
      binding of protein phosphatase-1 to its binding protein spinophilin. To better
      understand spinophilin's role in targeting protein phosphatase-1 within neurons,
      we used a combination of preembedding immunoperoxidase and postembedding
      immunogold labeling and electron microscopy to determine the localization of this
      scaffolding protein in macaque prefrontal cortex. Consistent with previous
      reports, spinophilin was found predominantly in dendritic spines, but a
      significant number of labeled dendritic shafts and, less frequently, glia and
      preterminal axons were also identified. By using the postembedding immunogold
      method, we further examined the distribution of spinophilin within dendritic
      spines. Spinophilin immunoreactivity was present throughout the spine, but the
      density of label was heterogeneous and defined two domains. The highest density
      of label was associated with the postsynaptic density and the 100 nm immediately
      subjacent to it. The deeper region of the spine, further than 100 nm from the
      postsynaptic density, had a lower density of spinophilin label. The distribution
      of spinophilin reported in this study supports its role in modulating
      glutamatergic neurotransmission but also suggests the possibility that
      spinophilin may target protein phosphatase-1 to other sites within the spine or
      to other neuronal or glial compartments.

PMID- 14694534
TI  - Mushroom body volumes and visual interneurons in ants: comparison between sexes
      and castes.
AB  - The mushroom bodies are brain centers involved in complex behaviors such as
      learning and orientation. Here we examine the organization of mushroom bodies in
      ants, focusing on visual input. We describe the structure of visual neurons and
      compare the volume of brain structures involved in visual processing, especially
      the optic lobes and parts of the mushroom bodies receiving visual input in males,
      winged females, and workers of carpenter ants (Camponotus). A relatively small
      number of neurons connect the medulla with the mushroom bodies, and these neurons
      have relatively large dendritic fields in the medulla, suggesting low spatial
      resolution in ants. These neurons terminate in different yet overlapping strata
      in the mushroom bodies' collar region. While males have larger optic lobes than
      workers, their collar region is smaller than in females. Male ants have an
      additional type of medulla-mushroom body neuron with dendrites probing the distal
      medulla. These neurons are absent in female and worker ants. Most mushroom body
      Kenyon cells that are postsynaptic to visual input neurons appear to integrate
      visual as well as antennal input. This is in contrast to honey bees, where visual
      input to the mushroom bodies is more prominent and where Kenyon cells are not
      known to combine visual and antennal input.

PMID- 14694535
TI  - Aberrant transcription of unrearranged T-cell receptor beta gene in mouse brain.
AB  - The nervous system and the immune system share several functional molecules
      involved in various cell-cell interaction events. In this study, we used in situ
      hybridization to identify immune molecules that are expressed by a restricted
      population of neurons in the mouse brain and found that mRNA for the beta subunit
      of T-cell receptor (TCRbeta) was predominantly and strongly localized to neurons
      in deep layers of the cerebral neocortex and weakly expressed in the thalamus.
      Developmentally, TCRbeta mRNA expression started at embryonic day 15 in the
      thalamic nuclei and at postnatal day 1 in the cerebral neocortex. The level of
      TCRbeta mRNA in the neocortex subsequently increased until postnatal day 21, and
      it remained high in the adult. Detailed analysis revealed that only the Cbeta2
      segment of TCRbeta, not the Cbeta1 or Vbeta segments, was expressed by the brain
      neurons. By the 5' rapid amplification of cDNA ends method, we determined a brain
      specific transcription start site in the Jbeta2 region locus, not in the Vbeta
      region locus. Furthermore, we confirmed that the aberrant transcription around
      the Jbeta2 region took place only in neurons and lymphocytes in transgenic mice.
      These results demonstrate that the transcriptional machinery for unrearranged
      TCRbeta expression is shared by the nervous and immune systems and raise a
      possibility of gene rearrangement in neurons under certain circumstances.

PMID- 14694536
TI  - Focused motor stereotypies do not require enhanced activation of neurons in
      striosomes.
AB  - Stereotypic motor behavior is a widespread phenomenon of many neurologic and
      psychiatric disorders. Studies on the mechanisms controlling motor stereotypies
      have focused on the role of dopamine in modulating the activity of basal ganglia
      neuronal circuits, and recent results demonstrated that stereotypic motor
      responses characteristic of psychomotor stimulant sensitization correlate with an
      enhanced activation of neurons located in striatal striosomes that substantially
      exceeds that of the surrounding matrix. The present study tested whether
      predominant striosomal activation is a general predictor for stereotypy. Wild
      type and dopamine D(2) and D(3) receptor knockout mice were treated either three
      times with methamphetamine (METH; 3 x 5 mg/kg every 2 hours) or once with a full
      D(1) agonist. Depending on the genotype, both treatments elicit the same focused
      stereotypy (taffy pulling). Repeated METH-treatment elicits intense stereotypy in
      wild-type and D(3) mutants but not in D(2) single and D(2)/D(3) double mutants.
      The stereotypic response of wild-type and D(3) mutants correlates with a
      predominant activation of neurons located in striosomes. No striosomal
      predominance is detected in METH-treated D(2) single and D(2)/D(3) double
      mutants. In contrast, D(2) single and D(2)/D(3) double mutants exhibited the most
      severe stereotypic response to D(1)-agonist treatment. However, this treatment
      did not result in enhanced striosomal activation. Thus, whereas the expression of
      stereotypy in response to repeated METH treatment requires D(2) receptor
      expression, D(2) receptor expression diminishes stereotypic responses to an acute
      dose of a D(1) agonist. Enhanced striosomal activation, however, is a reliable
      indicator of D(1)- and D(2)-receptor coactivation but not a predictor for
      repetitive motor behavior in general.

PMID- 14694537
TI  - An immunohistochemical and pathway tracing study of the striatopallidal
      organization of area X in the male zebra finch.
AB  - Area X is a nucleus within songbird basal ganglia that is part of the anterior
      forebrain song learning circuit. It receives cortical song-related input and
      projects to the dorsolateral medial nucleus of thalamus (DLM). We carried out
      single- and double-labeled immunohistochemical and pathway tracing studies in
      male zebra finch to characterize the cellular organization and circuitry of area
      X. We found that 5.4% of area X neuronal perikarya are relatively large, possess
      aspiny dendrites, and are rich in the pallidal neuron/striatal interneuron marker
      Lys8-Asn9-neurotensin8-13 (LANT6). Many of these perikarya were found to project
      to the DLM, and their traits suggest that they are pallidal. Area X also
      contained several neuron types characteristic of the striatum, including
      interneurons co-containing LANT6 and the striatal interneuron marker parvalbumin
      (2% of area X neurons), interneurons containing parvalbumin but not LANT6 (4.8%),
      cholinergic interneurons (1.4%), and neurons containing the striatal spiny
      projection neuron marker dopamine- and adenosine 3',5'-monophosphate-regulated
      phosphoprotein (DARPP-32) (30%). Area X was rich in substance P (SP)-containing
      terminals, and many ended on area X neurons projecting to the DLM with the woolly
      fiber morphology characteristic of striatopallidal terminals. Although SP+
      perikarya were not detected in area X, prior studies suggest it is likely that SP
      synthesizing neurons are present and the source of the SP+ input to area X
      neurons projecting to the DLM. Area X was poor in enkephalinergic fibers and
      perikarya. The present data support the premise that area X contains both
      striatal and pallidal neurons, with the striatal neurons likely to include SP+
      neurons that project to the pallidal neurons.

PMID- 14694538
TI  - Up-regulation of phosphorylated CREB but not c-Jun in bladder afferent neurons in
      dorsal root ganglia after cystitis.
AB  - We examined the changes of two transcription factors, CREB and c-Jun, in dorsal
      root ganglia (DRG) after acute (8 or 48 hours) or chronic (10 days)
      cyclophosphamide (CYP)-induced cystitis. Results showed an increase in the number
      of p-CREB-immunoreactive (-IR) cells in the L1 and L2 DRG (5-7-fold; P < or =
      0.05) as well as L6 and S1 DRG (2-4-fold; P < or = 0.05) after acute and chronic
      cystitis. The number of p-CREB-IR cells in the L4-L5 DRG was not altered with
      cystitis. The number of c-Jun-IR cells increased in the L1-L2 DRG (L1: 10-fold;
      L2: 8-fold; P < or = 0.05) only with chronic cystitis, although it increased in
      the L6-S1 DRG with CYP-induced cystitis of acute (2-3-fold; P < or = 0.05) and
      chronic (6-10-fold; P < or = 0.05) duration. After CYP treatment, the percentage
      of bladder afferent cells expressing p-CREB immunoreactivity (3-7-fold; P < or =
      0.05) increased in L1, L2, L6, and S1 DRG. The increase occurred 8 hours post-CYP
      injection and was maintained with chronic cystitis. There were few c-Jun-IR cells
      in the bladder afferent population. These results demonstrate that CYP induces p
      CREB and c-Jun expression in DRG in a time-dependent manner. However, c-Jun
      expression is not associated with bladder afferent neurons. Resiniferatoxin
      reduced CYP-induced up-regulation of p-CREB in DRG, suggesting that cystitis can
      reveal an altered CREB phosphorylation that may be mediated by capsaicin
      sensitive bladder afferents. Colocalization of p-CREB and Trk receptor(s) showed
      that a subpopulation of p-CREB-IR cells expressed p-Trk with cystitis. These
      results suggest that up-regulation of p-CREB may be mediated by a
      neurotrophin/Trk signaling pathway.

PMID- 14694539
TI  - Morphology and connections of nucleus isthmi pars magnocellularis in chicks
      (Gallus gallus).
AB  - The nucleus isthmi pars magnocellularis (Imc) and pars parvocellularis (Ipc)
      influence the receptive field structure of neurons in the optic tectum (TeO). To
      understand better the anatomical substrate of isthmotectal interactions, neuronal
      morphology and connections of Imc were examined in chicks (Gallus gallus).
      Cholera toxin B injection into TeO demonstrated a coarse topographical projection
      from TeO upon Imc. Retrogradely labeled neurons were scattered throughout Imc and
      in low density within the zone of anterogradely labeled terminals, suggesting a
      heterotopic projection from Imc upon TeO. This organization differed from the
      precise homotopic reciprocal connections of Ipc and the nucleus isthmi pars
      semilunaris (SLu) with TeO. By using slice preparations, extracellular
      biotinylated dextran amine injections demonstrated a dense projection from most
      neurons in Imc upon both Ipc and SLu. Intracellular filling of Imc neurons with
      biocytin revealed two cell types. The most common, Imc-Is, formed a widely
      ramifying axonal field in both Ipc and SLu, without obvious topography. A less
      frequently observed cell type, Imc-Te, formed a widely ramifying terminal field
      in layers 10-12 of TeO. No neurons were found to project upon both Ipc/SLu and
      TeO. Both types possessed local axon collaterals and flat dendritic fields
      oriented parallel to the long axis of Imc. Imc neurons contain glutamic acid
      decarboxylase, which is consistent with Imc participating in center-surround or
      other wide-field inhibitory isthmotectal interactions. The laminar and columnar
      pattern of isthmotectal terminals also suggests a means of interacting with
      multiple tectofugal pathways, including the stratified subpopulations of
      tectorotundal neurons participating in motion detection.

PMID- 14694540
TI  - Cell proliferation in the lamprey central nervous system.
AB  - After spinal cord transection, axons regenerate both in larval and adult
      lampreys. It is not known to what degree cells proliferate, even in the uninjured
      animal. Therefore, we have determined the prevalence of mitosis in the lamprey
      central nervous system (CNS). Bromodeoxyuridine (BrdU) was injected and
      incorporated for 4 hours into 2- to 5-year-old larvae, animals undergoing
      metamorphosis, and young adults. Labeled cells were counted in the
      rhombencephalon (where most supraspinal projecting neurons are located) and
      spinal cord. A mitotic index (MI) was calculated as the percentage of nuclei that
      were labeled. There was a seasonal variation in mitotic activity, with higher MIs
      occurring in summer. Within the summer, there was an additional transient spike
      in mitosis, especially in the rhombencephalon. There was no correlation between
      age and MI within the range of developmental stages examined. Baseline MIs in the
      rhombencephalon and spinal cord were approximately 0.15% and 0.20%, respectively.
      In most animals, the highest mitotic rates in both the rhombencephalon and spinal
      cord were seen in the ependyma, but many labeled cells were found in nonependymal
      regions as well. During the summer spike, almost all of the additional mitosis in
      the rhombencephalon was in the ependyma, but this finding was not true in the
      spinal cord. Many BrdU-labeled cells in the spinal cord and rhombencephalon were
      also stained by monoclonal antibodies specific for lamprey glial keratin but were
      never labeled by anti-neurofilament antibodies. These results suggest that (1)
      neurogenesis is uncommon in the lamprey CNS; (2) during most of the year,
      baseline gliogenesis occurs mainly in the ependyma with substantial contribution
      by nonependymal areas. During the summer, a spike of mitotic activity occurs in
      the ependyma of the rhombencephalon and throughout the spinal cord.

PMID- 14694541
TI  - [Pain therapy -- medicine of exceptions].

PMID- 14694542
TI  - [Nonorganic pain -- only psychogenic?].
AB  - Many chronic pain conditions cannot be classified correctly into the actual
      categories of nociceptive, neuropathic, or psychogenic pain. The experience that
      a therapeutic influence on the vegetative nervous system often improves these
      pains or induces healing of them suggests a classification into four pain types.
      The inclusion of the autonomic component in the appreciation, and the treatment
      of chronic pain conditions using measures acting on the vegetative nervous system
      (such as local anesthetics in the neural therapy of Huneke) will consistently
      enlarge and improve the understanding and the outcome in pain therapy.

PMID- 14694543
TI  - [Pathophysiology of pain and neural therapy].
AB  - Neural therapy according to Huneke uses the injection of local anesthetics for
      diagnosis and treatment. Depending on the situation, a stimulus (and/or the
      interruption of pathological stress) is given into the areas of the reflector
      segment or into the so-called "interference fields". This can trigger and
      maintain a disease or pain symptoms outside of every segmental order. Neural
      therapy targets autoregulatory mechanisms of the autonomic nervous system
      (especially the sympathetic nervous system). The theoretical principles for this
      include knowledge of neurophysiology and modern physics.

PMID- 14694544
TI  - [Do we need polysomnography in insomnia?].
AB  - The elimination of insurance coverage for polysomnography (PSG) in insomnia
      raised the question about the diagnostic value of this sole objective assessment
      of sleep. The methodology of PSG is described including the significant criteria
      for evaluating the recuperative value of sleep. Comparing clinical symptomatology
      and PSG shows, that the dominating symptoms are neither consistent nor specific,
      that the subjective evaluation of sleep by the patient is uncertain, and that
      extreme deviations may occur, especially in sleep state misperception. In the
      field of differential diagnosis, overlapping of insomnia with other disturbances
      within and outside the range of sleep medicine is frequent. Special problems
      arise in chronic non-organic pain. It is clear from all these aspects that PSG is
      indispensable in insomnia.

PMID- 14694545
TI  - [Fibromyalgia].
AB  - Fibromyalgia is a common syndrome. Rapid diagnosis and education of the patient
      are very important. "State of the art"-therapy is interdisciplinary and
      multimodal in a facility permitting coordinated and comprehensive management.

PMID- 14694546
TI  - [Psychotherapy for patients with chronic pain].

PMID- 14694547
TI  - [Breast feeding during the first few days after birth: sometimes insufficient].
AB  - Two newborn infants that were receiving breast-feeding were admitted to hospital
      for drowsiness and jaundice on the 6th and 4th day of life, respectively; these
      were a male infant that had been yellow since the very first day and a female
      infant that did not grasp the breast properly. Both recovered thanks to
      phototherapy and the administration of extra fluids. Seven days after discharge,
      the female infant was readmitted for the same symptoms, after which the breast
      feeding was found to be insufficient and the infant was put on bottle-feeding. In
      infants that are being breast-fed, insufficient intake can result in dehydration
      with all of its consequences. Such insufficient intake may be difficult to
      recognise. Weight loss greater than 5% implies that more frequent feeding is
      necessary and a loss of more than 10% may mean that supplementary feeding is
      necessary, albeit temporarily.

PMID- 14694548
TI  - [Treatment of the obstructive sleep-apnea syndrome in adults].
AB  - When treating the obstructive sleep-apnoea syndrome (OSAS), conservative
      management and the correction of treatable stenoses in the upper airway should be
      considered first. If these measures are neither effective nor applicable, then
      continuous positive airway pressure (CPAP) is the preferred treatment. Surgical
      interventions should only be considered after failure of non-surgical treatment
      modalities. Pharmacological management of OSAS is usually only indicated as a
      form of supplementary treatment in specific patients. Oral-appliance therapy
      appears to be of value in the management of OSAS and, in specific groups of
      patients, seems likely to offer a good alternative to CPAP in the future.

PMID- 14694549
TI  - [Chronic lung disease of the neonate; pathophysiology and treatment after the
      first weeks of life].
AB  - Chronic lung disease of the neonate sometimes occurs as a residual condition
      following respiratory distress in preterm infants. Improvements in neonatal
      intensive care treatment will in future lead to a greater number of children
      surviving chronic lung disease and reaching adulthood. The symptoms of the
      disease are hypoxaemia, hypercapnia, tachypnoea, subcostal and intercostal
      retractions, fluid retention, a reduced exertion tolerance and hyperreactive
      airways. The treatment after the first weeks of life is symptomatic and consists
      of: providing supplemental oxygen via a nasal mask or cannula (0.1-1 l/min);
      rapid downward adjustment of oxygen therapy may lead to more complaints and
      poorer growth; a normal fluid therapy; if there is a tendency towards fluid
      retention, then diuretic therapy is indicated and in severe cases fluid
      restriction as well; in the case of bronchial hyperreactivity: inhaled
      corticosteroids (the lowest effective dose for a period of several months) and a
      trial treatment with beta-agonists; in the case of persistent complaints or
      functional limitations, lung function tests can distinguish obstructive and
      restrictive disorders; vaccinations according to the national programme; consider
      vaccinations against influenza (age: 6-12 months) and respiratory syncytial virus
      (age < 2 years).

PMID- 14694550
TI  - [Optimalization of antibiotic policy in the Netherlands. VII. SWAB-guidelines for
      antimicrobial therapy in adults patients with infectious endocarditis].
AB  - The Working Party on Antibiotic Policy (Dutch acronym: SWAB) has developed
      guidelines for in-hospital antimicrobial therapy of adult patients with infective
      endocarditis. The choice and the duration of antimicrobial therapy are determined
      by the infecting micro-organism, the sensitivity of this micro-organism to
      antimicrobial therapy, the location of the endocarditis (left- or right-sided)
      and the presence of intracardial prosthetic material. While waiting for the
      culture results, the antibiotic treatment of an infected native valve is
      benzylpenicillin (in cases which begin subacutely or have a long history) or
      flucloxacillin (cases which begin acutely, are fulminant or in i.v. drug users),
      and gentamicin. If a prosthetic valve is infected then treatment of choice is
      vancomycin and gentamicin. Further antibiotic treatment depends on the causative
      micro-organism. Streptococci, enterococci and staphylococci are the most
      frequently occurring of these.

PMID- 14694551
TI  - [From gene to disease; congenital thrombotic thrombocytopenic purpura due to
      mutations in the ADAMTS13 gene].
AB  - Thrombotic thrombocytopenic purpura (TTP) is characterised by haemolytic anaemia
      with fragmented erythrocytes and thrombocytopenia, accompanied by other symptoms
      such as renal dysfunction, neurological signs and fever. Proteolysis of the Von
      Willebrand blood-clotting factor (VWF) by a VWF cleaving protease or ADAMTS13 is
      decreased in patients with TTP, leading to ultra-large Von Willebrand multimers
      in the circulation. A lack of ADAMTS13 activity can be caused by autoimmune
      inhibitors or may be due to a constitutional deficiency of this protein.
      Recently, the ADAMTS13 gene that encodes for the ADAMTS13 protein was found. It
      was mapped to chromosome 9q34 and consists of 29 exons. Several mutations have
      been identified in the ADAMTS13 gene in patients with the congenital form of TTP.
      Symptomatic episodes in congenital TTP can be prevented by prophylactic plasma
      infusions every 2-3 weeks, hereby preventing further organ damage due to
      thrombotic microangiopathy.

PMID- 14694552
TI  - [Diagnostic image (169). A man with partial atelectasis after an accident.
      Partial atelectasis on the right lower lobe due to a dislocated dental fragment].
AB  - A 23-year-old man fell from a height of 7 metres and developed partial
      atelectasis of the right lower lobe of the lung, due to a dislocated dental
      fragment.

PMID- 14694553
TI  - [Awareness and periconceptional use of folic acid among non-western and western
      women in the Netherlands following the 1995 publicity campaign].
AB  - OBJECTIVE: To investigate the influence of ethnicity on the awareness and use of
      folic acid by pregnant women. DESIGN: Secondary data analysis. METHOD: Using the
      data on 1555 women, collected during a cross-sectional study conducted among
      pregnant women with good knowledge of the Dutch language in 1996, the authors
      determined what was known about the recommendation to use folic acid around the
      time of conception and what the actual use was. Women were defined as either
      'western' or 'non-western' on the basis of the place of birth of the woman and
      her parents. RESULTS: Of the 1555 pregnant women, 74 (5%) were non-western or of
      non-western descent. Non-western women more often had a lower educational level
      than western women (51% versus 34%; p = 0.002) and more often had an unintended
      pregnancy (24% versus 8%; p < 0.0001). 41% of the non-western women had heard of
      the recommendation to use folic acid before pregnancy, compared to 79% of the
      western women (p < 0.0001). However, the use of folic acid was not significantly
      different between non-western and western women (56% versus 69%) if they had been
      aware of the recommendation to use folic acid before pregnancy. Awareness of the
      recommendation to use folic acid was higher in older women (OR: 1.46; 95% CI:
      1.13-1.89), women of western descent (0.27; 0.16-0.47), women with a higher level
      of education (0.35; 0.27-0.45) and in case of planned pregnancy (0.45; 0.31
      0.67). The use of folic acid, restricted to women who were aware of the
      recommendation to use folic acid before their pregnancy, was higher in older
      women (1.37; 1.05-1.80) and lower in those with more previous pregnancies (0.57;
      0.43-0.75) and in case of an unplanned pregnancy (0.55; 0.34-0.88). CONCLUSION:
      Although non-western women had less knowledge of the recommendation to use folic
      acid than western women, the use of folic acid was not significantly different
      from that by western women if they had been aware of the recommendation to use
      folic acid before pregnancy. Continued education on folic acid targeting non
      western and western women is important.

PMID- 14694554
TI  - [Follow up after an abnormal pap smear: time interval acceptable, nature of
      follow up leaves room for improvement].
AB  - OBJECTIVE: To investigate whether the interval between an abnormal Pap smear and
      follow-up is too long and whether the guidelines for histological follow-up after
      an abnormal Pap smear are being followed. DESIGN: Descriptive. METHOD: Data on
      all Pap smears of a minimum Pap class 3a (moderate dysplasia) from the national
      cervical-cancer screening programme in the Rotterdam area of the Netherlands were
      acquired from the Pathological Anatomical National Automated Archive (PALGA). The
      test results from each woman were arranged chronologically and the nature of the
      follow-up cervical examinations (cytological and histological) was recorded. The
      observation period was 360 days. The average interval in days between Pap smear
      and follow-up as well as the nature of the follow-up were analysed. RESULTS: In
      total, data on 156 women were analysed. In 93% of women follow-up was done during
      our observation period. The average interval was 60 days. In 80% of the women
      follow-up took place within 3 months and in 90% within 6 months. In 32% of women
      in the follow-up group the Pap smear was repeated at their first follow-up visit
      and in the remaining cases, a histological examination was performed according to
      the guidelines. In 7% of cases no cytological or histological follow-up at all
      took place within the year. CONCLUSION: The average interval between an abnormal
      Pap smear and follow-up is acceptable because of the slow natural course of
      cervical carcinoma. Attention should be focused on the incorrect repetition of
      the cytological test and on the fact that in a number of cases no follow-up at
      all is done within 1 year.

PMID- 14694555
TI  - [Nephrogenic fibrosing dermopathy].
AB  - A 58-year-old man with renal insufficiency, who was being treated by
      haemodialysis, developed progressive skin lesions. He had thickening and
      hardening of the skin at the extremities and swelling of the toes and fingers
      with flexion contractures. His face was not affected. Laboratory evaluation was
      unremarkable and a skin biopsy [table: see text] showed an increase of collagen
      and mucin, without an inflammatory infiltrate. These clinical features resemble a
      recently reported new disorder: nephrogenic fibrosing dermopathy. This disorder
      manifests as scleromyxedema-like cutaneous skin lesions without associated
      paraproteinemia, occurring in the setting of renal disease. The histopathologic
      features of nephrogenic fibrosing dermopathy, i.e. thickened collagen and mucin
      deposition, are unique. The incidence, prevalence and cause of the disease are
      unknown and there is currently no effective treatment. The Centers for Disease
      Control and Prevention (CDC) in the USA are calling on physicians who have
      encountered patients suffering from this type of lesions to contact the CDC for
      an intended control study.

PMID- 14694556
TI  - [Shigellosis, a sexually transmitted disease in homosexual men].
AB  - A study of the registered number of Shigella infections in Amsterdam for the
      period 1997-2001 revealed that in 2001, there was an increase in the number of
      homosexual patients with oral-anal contacts as source for their infections. All
      of these infections were caused by subtype Shigella sonnei. The infections were
      not associated with a specific meeting place for homosexual men. A relationship
      with an underlying HIV-infection is likely.

PMID- 14694557
TI  - [Simplified diagnosis of deep venous thrombosis by applying clinical score and D
      dimer concentration].

PMID- 14694558
TI  - [Arterial hypoxemia due to packing of the nose].

PMID- 14694559
TI  - [Clinical reasoning and decision making in practice. A 41-year old with periodic
      fever of unknown origin].

PMID- 14694560
TI  - [Clinical reasoning and decision making in practice. A 41-year old with periodic
      fever of unknown origin].

PMID- 14694561
TI  - [Clinical reasoning and decision making in practice. A 41-year old with periodic
      fever of unknown origin].

PMID- 14694562
TI  - [Androgens, well-being and libido in women].

PMID- 14694563
TI  - [Androgens, well-being and libido in women].

PMID- 14694564
TI  - What's right with nursing.

PMID- 14694565
TI  - Change your world--volunteer.

PMID- 14694566
TI  - Overcoming the top 10 tracheotomy self-care learning barriers.
AB  - Multispecialty inpatient units are the norm in today's acute care settings. Since
      few units have the luxury of seasoned otorhinolaryngology (ORL) nurses, care of
      the postoperative patient with a tracheotomy, including discharge teaching and
      planning are left to the generalists. Generalist nurses and new ORL nurses may
      find themselves experiencing fear and anxiety along with the tracheotomy patients
      they care for and teach. Experienced ORL nurses are continually challenged to
      find ways to share their expertise with patients and less experienced nurses in
      effective ways. This article presents a unique approach to preparing nurses to
      teach self-tracheotomy care to their patients. Medical-surgical staff nurses
      attended a 90-minute inservice program presenting actual clinical scenarios of
      temporarily learning-impaired patients with tracheotomies, and were asked to role
      play effective interventions. The program content is designed to address the
      reluctance of inexperienced, busy nurses to confront learning barriers and
      motivate patients to accomplish early postoperative involvement in tracheotomy
      self care. The widespread nature of the challenges faced by nurses and patients
      regarding tracheotomy care has been confirmed by discussions with colleagues on a
      national level. It has been confirmed further by the first author's clinical
      experiences in a wide variety of health care settings. Recommended nursing
      actions and responses to learning barriers presented here are based on expert
      opinion and clinical experience.

PMID- 14694567
TI  - Fire in the OR: this can't be happening to me.

PMID- 14694568
TI  - NIWI 2000: issues and opportunities.
AB  - The Nurse in Washington Internship (NIWI) is a four-day annual program sponsored
      by the National Federation of Specialty Nursing Organizations (NFSNO). Aside from
      presenting a dynamic educational experience, NIWI enables nurses to actively
      participate in the legislative process by spending a day on Capitol Hill. The
      2000 NIWI focused on several issues of importance to nurses and nursing practice.
      This article discusses those issues.

PMID- 14694569
TI  - Of specialty interest: how to start a local chapter.

PMID- 14694570
TI  - A betrayal of trust?

PMID- 14694571
TI  - Mothers' helpers?
AB  - This brief review comes at a time when there is interest in grandparents as
      sources of help and support for younger generations, both for their own families
      and also in the wider intergenerational community (Box 1). 'Special' populations
      of grandparents are being identified as playing major roles in childcare but
      these may have high health needs. Being a grandparent is generally a positive
      role for older people and for some may be satisfying and enjoyable and endure
      over many decades.

PMID- 14694572
TI  - Ageism in renal replacement therapy.

PMID- 14694573
TI  - SHARP practice: joining up care giving and record keeping.

PMID- 14694574
TI  - Constipation: identifying the problem.
AB  - Constipation is a common problem in older age and a costly one, both in terms of
      treatment and distress caused to patients. This article describes the causes of
      constipation and outlines various strategies nurses can employ to identify and
      assess it.

PMID- 14694575
TI  - Calcium antagonists and their use with older people.

PMID- 14694576
TI  - Age and opportunity?

PMID- 14694577
TI  - A long standing friend. Interview by Debbie Andalo.

PMID- 14694578
TI  - Consultant nurses in children's services.

PMID- 14694579
TI  - Worthing's modern matron experience: the first year.

PMID- 14694580
TI  - Sharing experiences and learning.

PMID- 14694581
TI  - Governing principles.

PMID- 14694582
TI  - Acting or reacting?

PMID- 14694583
TI  - [Study on the effect using hemoperfusion to treat tetramine poisoned patients].
AB  - OBJECTIVE: To evaluate the effect of hemoperfusion on tetramine poisoned
      patients. METHODS: Three tretramine poisoned cases treated with hemoperfusion
      were selected. The samples during and after hemoperfusion were collected and
      analyzed by gas chromatography. RESULTS: Tetramine concentration at the inlet of
      the artificial kidney kept the same level during hemoperfusion. After
      hemoperfusion, the tetramine concentration in patient plasma changed little in 72
      hours. 1.03-1.55 mg of tetramine was adsorbed by the instrument of hemoperfusion
      after two hours' hemoperfusion. CONCLUSION: Although hemoperfusion was not so
      effective to reduce blood tetramine concentration in patients, it could clear
      about 1 mg tetramine for one time.

PMID- 14694584
TI  - [Comparison of the toxic effect of methamidophos and acephate on
      acetylcholinesterase].
AB  - OBJECTIVE: To explore the inhibitory effects of highly toxic organophosphorus
      compound and its substitute (methamidophos and acephate) on acetylcholinesterase
      (AChE) and their toxic mechanisms. METHODS: Ellman method was used to measure
      AChE activity in vitro and vivo. RESULTS: Acephate and methamidophos could
      directly inhibit AChE activities in human erythrocyte membrane and rat brain
      synatosomal membrane in dose- and time-dependent manners in vitro, and this
      effect was irreversible. The IC50 of acephate and methamidophos affecting human
      erythrocyte membrane and rat synatosomal membrane were approximately 10(-4) mol/L
      and 10(-5) mol/L respectively and the Ki were 10(2) mol.L-1.min-1 and 10(3) mol.L
      1.min-1 respectively. In vivo, after rats being administered with them for 5 d,
      the inhibitory rate of AChE activities in blood were increased to 68.24% and
      54.80% respectively. When rats being administrated with acephate, there was
      31.68% of inhibition on the brain stem, but no significant inhibition in other
      brain region was noticed, while methamidophos had a strong inhibitory effect on
      the activity of AChE in all brain regions, especially the cerebellum and brain
      stem(71.51% and 61.85% respectively). CONCLUSION: Acephate and methamidophos
      could directly inhibit the AChE activities in vitro, but the inhibition degree
      was different. In vivo, both could also inhibit AChE activities in blood. The
      difference in inhibition on brain regions may be one of the reason of various
      toxic effect of them.

PMID- 14694585
TI  - [Lipoxygenase-mediated N-demethylation of pesticides in vitro].
AB  - OBJECTIVE: In order to explore the pathway of dealkylation of pesticides other
      than cytochrome P450 monocoxygenases, lipoxygenase (LOX)-mediated demethylation
      of aminocarb and some other pesticides were measured. METHOD: Formaldehyde
      generated in the reaction was estimated by Nash reaction to express the rate of
      demethylation of pesticides mediated by soy lipoxygenase (SLO). RESULTS: N
      demethylation of aminocarb mediated by SLO was found to depend on the incubation
      time, concentration of the enzyme, concentration of aminocarb and hydrogen
      peroxide. Under optimal conditions, Vmax value of 18 nmol of formaldehyde.min
      1.nmol-1 of lipoxygenase was observed. The reaction exhibited Km values of 3.4
      mmol/L for aminocarb and 235 mumol/L for hydrogen peroxide. A strong inhibition
      of the reaction by nordihydroguaiaretic acid, gossypol, and phenidone clearly
      implicated the lipoxygenase involvement as the protein catalyst. A significant
      decline in the formaldehyde accumulation in the presence of either reduced
      glutathione or dithiothreitol suggested generation of a free radical species as
      an initial oxidation intermediate during the demethylation of aminocarb by SLO.
      The inhibition of formaldehyde generation by butylated hydroxyanisole(BHT) and
      butylated hydroxy toluene(BHA) further supported this contention. In addition to
      aminocarb, seven other pesticides were also found to undergo N-demethylation,
      albeit at relatively low rates. CONCLUSION: Certain pesticides may oxidatively
      undergo dealkylation via the lipoxygenase pathway in animals and plants.

PMID- 14694586
TI  - [Study on monitoring and clearing of organophosphate in blood in organophosphate
      poisoned rats].
AB  - OBJECTIVE: To study the new method of monitoring and clearing organophosphate in
      blood during single or mixed organophosphate(OP) poisoning. METHOD: (1) Mixed
      equal volumes of blood of OP poisoned rat and healthy rat, then determine whole
      blood cholinesterase (ChE) activity. The descending range of ChE activity
      represents the level of residual OP in blood. (2) Poisoned rats by single or
      mixed OP pesticides were injected with 5% NaHCO3 15 ml/kg intraperitoneally, then
      the level of OP in blood was detected. RESULTS: (1) The monitoring results of
      blood residual OP by gas chromatography were similar to that by "Mixes blood
      method", which showed significant difference(P < 0.05) from that before OP
      administration. (2) NaHCO3 injection could not improve the toxic symptoms and
      whole blood or brain ChE inhibition in 10 CP poisoned rats, blood residual OP
      level was also not affected, but lung pathological changes by OP such as
      interstitial inflammation and oedema showed some relief. CONCLUSION: The
      monitoring of blood ChE by "mixed blood method" may reflect the general level of
      the blood residual OP within the range of exposure dose. The effect of NaHCO3 was
      not satisfactory, but it may improve OP-induced lung pathological changes.

PMID- 14694587
TI  - [The activity of blood cholinesterase in rats exposed to dimehypo].
AB  - OBJECTIVE: To determine whether and to what degree the activity of
      cholinesterase(ChE) is inhibited by dimehypo at different doses of dimehypo
      [scientific name: 2-dimethylamine-1,3-bi(sodium hyposulfit)]. METHOD: Rats were
      dosed with dimehypo or methamidophos orally, and were randomly divided into four
      subgroups according to the pesticide doses, which were 1/16, 1/8, 1/4 and 1/2 of
      LD50 respectively(the LD50 of dimethypo and methamidophos is 342 mg/kg and 20
      mg/kg respectively). The activity of ChE in blood was determined before and 30
      min, 1, 2, 4 and 24 h after exposure. The modified Ellman Method was employed to
      measure the activity of ChE. RESULT: 1/16 LD50 dose of dimehypo did not affect
      the activity of ChE. When the dose increased, the activity of ChE decreased
      accordingly. 1/2 LD50 dose of dimehypo inhibited the activity of ChE by 35.9%
      compared with that of control group(P < 0.01). In rats dosed with methamidophos,
      even 1/16 LD50 dose inhibited the activity of ChE by 42.4% compared with that of
      control group. When the dose of methamidophos increased, the activity of ChE
      decreased accordingly. 1/2 LD50 dose of methamidophos inhibited the activity of
      ChE by 52.9%. The activity of ChE in the rats dosed with dimehypo at various
      doses was significantly lower than that in the rats dosed with corresponding
      doses of methamidophos(P < 0.01). CONCLUSION: Higher doses of dimehypo may
      inhibit the activity of ChE. However, as compared with methamidophos, dimehypo is
      a weaker inhibitor of ChE.

PMID- 14694588
TI  - [The activity of blood cholinesterase in rats exposed to dimethypo after drug
      intervention].
AB  - OBJECTIVE: To investigate the activity of ChE in rats poisoned by dimehypo and
      then treated with pralidoxime methylchloride or unithiol. METHOD: Rats were
      divided into control group (dimehypo); intervention groups [dimehypo plus
      pralidoxime methylchloride or dimehypo plus unithiol (sodium
      dimercaptopropanesulphonate)]. Rats were dosed with 4 different doses of
      dimehypo: 1/16, 1/8, 1/4 and 1/2 of LD50 respectively(the LD50 of dimehypo is 342
      mg/kg). After being poisoned with dimehypo orally, rats were immediately injected
      intramuscularly with pralidoxime methylchloride or unithiol. The activity of ChE
      in blood was detected before and 1/2, 1, 2, 4 and 24 h after poisoning in
      dimehypo and intervention groups. RESULT: The ChE activity of four dose subgroups
      at 1 h after poisoning were (1.04 +/- 0.21), (0.84 +/- 0.12), (0.71 +/- 0.12),
      (0.66 +/- 0.07) U/ml respectively; the ChE activity of pralidoxime methylchloride
      intervention groups were (1.01 +/- 0.18), (1.17 +/- 0.11), (1.01 +/- 0.04), (1.03
      +/- 0.12) U/ml respectively; and the ChE activity of unithiol intervention groups
      were (1.15 +/- 0.15), (1.26 +/- 0.27), (1.08 +/- 0.08), (1.04 +/- 0.12) U/ml
      respectively. The inhibited ChE in blood was recovered by either treatment with
      pyraldoxime methylchloride or unithiol. These two drugs had similar effects of
      recovering the activity of ChE(P > 0.05), but at higher doses(1/4 and 1/2 of
      LD50) the effects of both were not so good. CONCLUSION: Pralidoxime
      methylchloride and unithiol could partly recover the activity of ChE inhibited by
      dimehypo.

PMID- 14694589
TI  - [Effect of deltamethrin on benzyloxyresorufin O-dealkylatase activity and
      CYP2B1/2B2 protein level in rat brain].
AB  - OBJECTIVE: To detect the effect of deltamethrin (DM) on benzyloxyresorufin O
      dealkylatase (BROD) activity and the expression of CYP2B1/2B2 in rat brain.
      METHODS: BROD activity was determined by fluorophotometry under the treatment of
      DM in vivo and vitro. Western-blot analysis was used to detect the expression of
      CYP2B1/2B2. RESULTS: In vivo, DM could markedly inhibit BROD activity in rat
      brain microsome after rats had been treated with DM (12.5 mg.kg-1.d-1, i.p.) for
      5 days. The inhibitory rate in whole brain, cerebral cortex and cerebellum were
      26.7%, 23.8% and 33.3% respectively(P < 0.05). However, in vitro, under the
      concentration of 2 x 10(-8)-2 x 10(-4) mol/L of DM, there was no obvious change
      of BROD activity in rat brain. Moreover, Western-blot analysis indicated that DM
      could significantly reduce the expression of CYP2B1/2B2 in vivo, the inhibitory
      rate of protein synthesis was 42.6%. CONCLUSION: DM could inhibit BROD activity
      in rat brain and this effect may be related to the reduction of CYP2B1/2B2
      protein synthesis.

PMID- 14694590
TI  - [The neuromuscular transmission effects induced by pralidoxine chloride on rats
      with acute isocarbophos poisoning].
AB  - OBJECTIVE: To study the effects of improving the neuromuscular transmission
      (NMT), "non-AChE-reactivating effects", by oximes in treating acute isocarbophos
      poisoning. METHODS: The effect of pralidoxime chloride(PAM-Cl) on the
      neuromuscular transmission(NMT) in rats exposed to isocarbophos was studied by
      using the stimulation single fiber electromyography (SSFEMG) to determine the
      single fiber action potential. RESULTS: After the rats exposed to isocarbophos
      were treated by PAM-Cl, the mean consecutive difference(MCD) value [(25.99 +/-
      5.84) microsecond] of single fiber action potential was significantly lower than
      that before PAM-Cl treatment [(33.21 +/- 4.09) microsecond, (P < 0.01)], but no
      AChE reactivation in blood and gastrocnemius was observed. CONCLUSION: PAM-Cl has
      "non-AChE-reactivating effects", it could markedly improve isocarbophos-induced
      NMT block of gastrocnemius.

PMID- 14694591
TI  - [Effects of deltamethrin on intracellular free Ca2+ concentration and apoptosis
      in rat neural cells].
AB  - OBJECTIVE: To study the effects of deltamethrin on intracellular free Ca2+
      concentration and apoptosis in rat neural cells. METHODS: Wister rats were
      randomly divided into 4 groups(3 treated groups and 1 control). Intracellular
      free Ca2+ concentration in rat neural cells was measured by using the fluorescent
      Ca2+ indicator Fura-2/AM. Apopotic rate of neural cells was measured by using
      FACS420 Flow Cytometer. RESULTS: Intracellular free Ca2+ concentration at 5 h
      after deltamethrin exposure [hippocampus: (389.94 +/- 43.64) nmol/L, cerebral
      cortex: (449.33 +/- 23.23) nmol/L], at 24 h[hippocampus: (340.47 +/- 32.36)
      nmol/L, cerebral cortex: (311.62 +/- 25.48) nmol/L] and at 48 h[hippocampus:
      (287.13 +/- 24.29) nmol/L, cerebral cortex: (346.55 +/- 36.87) nmol/L] were all
      higher than those of the control group[hippocampus: (203.24 +/- 18.53) nmol/L,
      cerebral cortex: (226.85 +/- 14.81) nmol/L, P < 0.01]; Apoptotic rate in neural
      cells 24 h and 48 h later [hippocampus: (8.45 +/- 1.02)%, (9.44 +/- 1.14)%,
      cerebral cortex: (7.90 +/- 0.49)%, (8.01 +/- 0.87)%] were also higher than those
      of the control group[hippocampus: (2.97 +/- 0.36)%, cerebral cortex: (3.50 +/-
      0.48)%, P < 0.01)] and increased with time prolonged. CONCLUSION: Exposure to
      high dose of deltamethrin would interfere with intracellular free Ca2+
      concentration and apoptotic rate in rat neural cells, suggesting that there may
      be certain relation between them.

PMID- 14694592
TI  - [Assessment of risk for tin mine dust in Guangxi].
AB  - OBJECTIVE: To explore the minimum observed adverse effect level(LOAEL) and
      intensity of pathogenesis of tin mine dust. METHODS: A cohort study design with
      retrospective assessment of exposure was used. Selected 4,471 male tin miners who
      were exposed to tin at least one year during 1960 to 1974 and were compared with
      4,797 pottery dust exposed workers in the same way designed. Statistical analysis
      system SAS, PROC LIFETEST were used to perform the non-parameter calculation by
      Life Table method. RESULTS: Tin mine cohort subjects were followed up to December
      31, 1994. The percentage of miners who developed silicosis was 21.7% (971/4,471).
      81% of the patients had been exposed to dust before 1958. The cumulative total
      dust exposure(CTD) was significantly correlated with silicosis risk. The risk of
      silicosis was 0.012 when CTD was less than 50 mg/m-3.year-1. The risk of
      silicosis was increased to 0.971 when CTD was beyond 400 mg.m-3.year-1. However,
      the risk of silicosis was only 0.369 for dust exposed workers in pottery
      factories when CTD was beyond 400 mg.m-3.year-1. CONCLUSION: There was
      significant relationship between cumulative dust exposure and the incidence of
      silicosis in tin exposed workers. And silicosis induced by tin mine dust is more
      serious than the pottery dust.

PMID- 14694593
TI  - [An investigation on dust exposure level in workers of geological prospecting
      occupation].
AB  - OBJECTIVE: To make sure of the harmfulness degree of the dust in geological
      prospecting occupation. METHODS: The determination of respirable dust, total dust
      and the free silica concentrations was carried out at different working spots
      exposed to dust. Personal sampling equipment was used to collect the respirable
      dust. The data of respirable dust concentration in the research was compared to
      the historical data. RESULTS: As for respirable dust concentration level, 47.95%
      of 765 silica dust spots of geological prospecting occupation in 9
      provinces(autonomous regions) were beyond the criteria. The profession and work
      type of the highest dust concentration was chiseling and sampling of geological
      prospecting [from 1996-2000, the dust concentration was (6.15 +/- 3.12) mg/m3].
      The ratio of respirable dust to total dust was high in geological prospecting
      workers. The FSiO2 contentin dust to which geological prospecting workers exposed
      was high too. CONCLUSIONS: The respirable dust concentration of some types of
      work in geological prospecting occupation was obviously higher than the national
      criteria, especially in chiseling, sampling and drilling workers.

PMID- 14694594
TI  - [Appropriate dust control measures for jade carving operations].
AB  - OBJECTIVE: To provide the appropriate dust control measures for jade carving
      operations. METHODS: Dust concentrations in the workplace were measured according
      to GB/T 5748-85. Ventilation system of dust control were measured according to
      GB/T 16157-1996. Dust particle size distributions for different sources and
      particle size fraction collecting efficiencies of the dust collectors were
      measured with WY-1 in-stack 7 stage cascade impactors. RESULTS: On the basis of
      adopting wet process in the carving operations, local exhaust ventilation system
      for dust control was installed, which included: the special designed slot exhaust
      hoods with hood face velocity of 2.5 m/s and exhaust volume of 600 m3/h. The pipe
      sizes were determined according to the air volume passing through the pipe and
      the reasonable air velocities. Impinging scrubber or bag filter dust collector
      were selected to treat the dust laden air from the local exhaust ventilation
      system, which gave a total collecting efficiency of 97% for impinging scrubber
      and 98% for bag filter; The type of fan and its size were selected according to
      the total air volume of the ventilation system and maximum total pressure needed
      for the longest pipe line plus the pressure drop of the dust collector.
      CONCLUSIONS: Practical application showed that, after installation and use of the
      appropriate dust control measures, the dust concentrations in the workplaces
      could meet or nearly meet the national hygienic standard and the dust laden air
      at the local exhaust ventilation system could meet the national emission
      standard.

PMID- 14694595
TI  - [Immune responses of silicotic rats to the antigen of sheep red blood cells].
AB  - OBJECTIVE: To explore the immune response of silicotic rats to sheep red blood
      cells(SRBC). METHODS: Silicotic rats were immunized with SRBC by tracheal
      instillation(Group 1) or intraperitoneal injection (Group 2), and non-silicotic
      rats were immunized by tracheal instillation as normal control(Group 3). The
      levels of serum hemolytic index(HC50) were measured on 7, 12, 20, 25, and 32 days
      after primary immunization and 5, 12, 15 days after the second immunization.
      Special anti-SRBC IgG was measured with ELISA(A490 nm) on 12, 20, 25, 32 days and
      5, 12, 15, 27 days respectively. Delayed-type hypersensitivity(DTH) to SRBC was
      measured 20 days after second immunization and DTH reaction was determined at 24,
      48, 72, and 96 h after administration. Total cell count and cell populations in
      the bronchoalveolar lavage fluid(BALF), lung associated lymph node(LALN) and
      spleen weight, special IgG secreted from spleen cells were measured at the end of
      the experiment. RESULTS: The HC50 of Group 1(47.4 +/- 1.0, 52.2 +/- 4.6, 31.1 +/-
      11.9, 43.8 +/- 3.5, 33.6 +/- 16.8, 49.0 +/- 2.3, 92.9 +/- 20.2, 87.7 +/- 5.2)
      were statistically higher than those of Group 3(40.4 +/- 10.6, 2.8 +/- 2.5, 0.8
      +/- 0.6, 6.6 +/- 5.8, 1.4 +/- 0.1, 36.5 +/- 16.5, 53.0 +/- 33.2, 2.6 +/- 2.2).
      The special anti-SRBC IgG response in Group 1(1.67 +/- 0.19, 1.98 +/- 0.36, 1.12
      +/- 0.50, 1.38 +/- 0.30, 2.75 +/- 0.15, 2.60 +/- 0.28, 2.86 +/- 0.10, 2.50 +/-
      0.20) were much stronger than those in Group 3 (0.59 +/- 0.30, 0.56 +/- 0.21,
      0.21 +/- 0.16, 0.22 +/- 0.01, 0.81 +/- 0.25, 0.74 +/- 0.25, 0.69 +/- 0.26, 1.38
      +/- 0.41). Furthermore, the results of DTH showed positive response and the
      ratios for diameter of skin rash > 5 mm at 24, 48, 72, 96 h were 16/16, 16/16,
      16/16, 15/16 respectively in Group 1, while those in Group 3 were 8/15, 1/15,
      1/15, 1/15 respectively. Total cell count in the BALF, LALN and spleen weight,
      and special IgG secreted from spleen cells in Group 1 were higher too. Group 2
      expressed almost of the same but with mild immunologic responses as Group 1.
      CONCLUSION: Silicosis-induced extremely strong DTH and over-response of humoral
      immunity to some antigens may contribute to the likelihood of silicosis
      complicated with tuberculosis.

PMID- 14694596
TI  - [Effect of benzo[a]pyrene on DNA damage and expression of genes involved in
      nucleotide excision repair in lung cancer cells].
AB  - OBJECTIVE: To investigate the effect of benzo[a] pyrene(BaP) on DNA damage and
      expression of genes involved in nucleotide excision repair[xeroderma pigmentosum
      group B, C, G(XPB, XPC, XPG) and excision repair cross-complementing 1 (ERCC1)]
      in lung cancer A549 cells. METHODS: Cell survival was measured using MIT
      metabolic viability assay. Single cell gel assay was applied to determine the DNA
      damage and repair. The level of gene expression was measured by reverse
      transcription-polymerase chain reaction. RESULTS: The cell survival decreased
      from 95.0% to 70.0% after 24 h treatment with BaP of varying concentration
      ranging 0.625-20.000 mumol/L. The cell survival decreased to 87.0% and 73.0%
      respectively after 12 h and 24 h treatment with 10 mumol/L BaP, with DNA damage
      gradually elevated. At 12 h after 24 h treatment, the cell survival further
      decreased to 59.0% and DNA damage became most serious. At 24 h after 24 h
      treatment, cell survival recovered to 71.0%, and damaged DNA was repaired
      gradually. XPB and XPC gene expression increased to 4.5-fold and 11.2-fold
      respectively compared with basal level at 24 h treatment or 12 h after 24 h
      treatment with 10 mumol/L BaP respectively. However, ERCC1 and XPG gene
      expression was inhibited in 24 h treatment period, then recovered gradually after
      treatment. CONCLUSION: Benzo[a]pyrene could lead to DNA damage and expression
      level change of genes involved in nucleotide excision repair in lung cancer A549
      cells.

PMID- 14694597
TI  - [Changes in bronchoalveolar lavage fluid of rats exposed to metal grinding
      dusts].
AB  - OBJECTIVE: To investigate the effects of composite grinding dusts on rat
      respiratory system. METHODS: Rats were administrated with grinding dusts by
      intratracheal injection. After 2 weeks, the total numbers of cells, the
      percentage of differential cell, the survival rate of cell, and the activity of
      lactate dehydrogenase(LDH) and alkaline phosphatase(ALP) in bronchoalveolar
      lavage fluid were analyzed. RESULTS: Along with increasing concentration of
      grinding dusts, the total number of cells in lavage also increased, and was more
      than that in quartz group. Compared with control group, the percentage of
      neutrophil in lavage of rats treated with grinding dust and quartz significantly
      increased and meanwhile that of macrophage significantly decreased[PMN: quartz
      group (33.83 +/- 4.54)%; grinding dusts group (26.50 +/- 3.99)%, (36.00 +/-
      3.58)%, (38.00 +/- 2.10)% at 10, 25, 50 mg/ml respectively. Macrophages: quartz
      group (62.17 +/- 4.54)%; grinding dusts group (70.83 +/- 3.66)%, (60.83 +/-
      2.14)%, (58.17 +/- 2.48)%] while those in control group were (2.83 +/- 0.75)%,
      (95.67 +/- 1.21)% respectively. The cell survival rate in lavage in control group
      was 80%, but that in grinding dust and TiO2 group significantly decreased(P <
      0.01). The activity of LDH and ALP in all rats treated with dusts obviously
      increased, and there was significant difference compared with control group(P <
      0.01 or P < 0.05). Furthermore, there was significant difference between grinding
      dust group and quartz group, and between grinding dust group and TiO2 group
      respectively. CONCLUSION: Metal grinding dust is very harmful to rat's lung cells
      and may cause fibrogenesis in the lungs.

PMID- 14694598
TI  - [Study on the method for demonstrating dust granules in phagocytes with Warthin
      Starry special staining].
AB  - OBJECTIVE: To search a method for showing dust granules in phagocytes. METHODS:
      The autopsy samples of 10 cases who died of non-pulmonary diseases(group A), 6
      cases with silicosis(group B) and 5 cases of dead fetus(group C) were collected.
      The samples of lung, spleen and lymphnodes were stained by methods of (1)HE
      staining; (2)Warthin-Starry staining(W-S staining) and modified W-S staining; (3)
      CD68 (as a first antibody) immunohistochemical staining. The ultrastructure and
      chemical component of the dust granules in the pulmonary phagocytes(dust cells)
      of group A(3 cases) and group B(3 cases) were observed and analyzed by
      transmission electron microscope(TEM) and analytic electron microscope(AEM).
      RESULTS: In group A and B smaller or minute dust granules which could not be
      shown by HE staining method were clearly shown by W-S staining and modified W-S
      staining methods. There were no positive granules found in group C. The CD68
      marker of the dust cells was positive. The size, shape, density and chemical
      elements of the dust granules of group A were different from those of group B
      under TEM and AEM, excluding bacteria and other intracellular contents.
      CONCLUSION: The dust granules in the phagocytes could be shown by W-S staining
      method, its staining effect for minute dust granules is superior to general HE
      staining. However, the determination of chemical elements of dusts must depend on
      AEM.

PMID- 14694599
TI  - [Localization of the connexin 43 gap-junction protein in silica-exposed alveolar
      epithelial cells].
AB  - OBJECTIVE: To study the effect of supernatants from silicon dioxide(SiO2)
      stimulated pulmonary alveolar macrophages(PAM) on the localization of connexin
      43(Cx43) so as to explore the inhibition level of SiO2 on alveolar epithelial
      cellular gap-junctional communication(GJIC). METHODS: The supermatants from the
      primary cultured PAM were prepared, and then added 5% (v/v) SiO2 into 2% (v/v)
      NBS RPMI 1640 to stimulate the normal mink lung epithelial cell line CCL-64 for
      24 hours. The localizations of Cx43 in CCL-64 were analyzed by indirect
      immunofluorescence histochemistry and laser confocal scanning microscopy(LCSM).
      RESULTS: The normal cultured CCL-64 cells displayed bright membrane-associated
      Cx43 plaques labeling and formed dashes at regions of intercellular junction.
      Being exposed to supernatants from SiO2-stimulated PAM, the CCL-64 cells retained
      a relative low degree of Cx43 labeling at the cell periphery, localized in
      cytoplasm, and the individual spot, rather than plaques, were smaller compared to
      normal cultured cells. Along with the increase of the concentrations of SiO2, the
      cells displayed a different staining pattern, with clear cluster labeling
      aggregating towards the nucleus. CONCLUSION: The altered localization of the gap
      junctional protein Cx43 in alveolar epithelial cells, mediated by SiO2, indicated
      that the internalization of Cx43 may contribute to the inhibition on GJIC in
      silica-induced lung epithelium injury.

PMID- 14694600
TI  - [Changes of phosphorylation states of Cx43 protein in Chinese hamster lung cells
      induced by SiO2].
AB  - OBJECTIVE: To investigate whether cellular gap-junctional communication(GJIC)
      down-regulation and the internalization of connexin 43(Cx43) in Chinese hamster
      lung fibroblasts (CHL) induced by silica-stimulated pulmonary alveolar
      macrophages (PAM) supermatant is related with the phosphorylation states of Cx43
      protein. METHODS: Western-blot analysis was used to identify phosphorylated Cx43
      species. RESULTS: Samples from membrane protein, total protein and nucleoprotein
      in CHL cells with 50-500 micrograms/ml doses of silica-stimulated PAM
      supernatants showed NP, P1, P2, P3 four immunoreactive bands of Cx43 protein by
      contrast with the control group and 0 microgram/ml SiO2 group. And with the dose
      of SiO2 increased, the increment of the levels of P2 and P3 was observed.
      Moreover, the groups treated with SiO2 and protein kinase C inhibitor, Palmitoyl
      DL-Camitine chloride (PMC), simutaneously showed reduced level of P2 and P3, as
      compared with the groups treated with SiO2 only. CONCLUSION: The inhibition of
      GJIC and the internalization of Cx43 by SiO2 in CHL cells may relate to the
      changes of phosphorylation states of Cx43, and its mechanism may be similar to
      that of phorbol 12-myristate 13-acetate (TPA), i.e. via PKC activation pathway.

PMID- 14694601
TI  - [Changes of phosphorylation states of Cx43 protein in CCL-64 cells induced by
      SiO2].
AB  - OBJECTIVE: To investigate whether the cellular gap junctional communication(GJIC)
      down-regulation in alveolar epithelial cells (CCL-64 cells) induced by silica
      stimulated pulmonary alveolar macrophages (PAM) supernatant is related with the
      phosphorylation states of connexin 43(Cx43) protein. METHOD: Western-blot
      analysis was used to identify phosphorylated Cx43 species. RESULTS: Western-blot
      analyses of SiO2- and phorbol 12-myristate 13-acetate(TPA)-treated CCL-64 cells
      showed the same phosphorylation states of Cx43 as the control group. There were
      no Cx43 protein in nucleus of CCL-64 cells. CONCLUSION: The inhibition on GJIC
      induced by SiO2 and TPA in CCL-64 cells may not be brought about by altering the
      phosphorylation states of Cx43.

PMID- 14694602
TI  - [A monitoring study of electromyography median frequency on fatigue of erector
      spinalis in drivers working at high altitude].
AB  - OBJECTIVE: To evaluate the role of muscle fatigue in the pathogenesis of high
      prevalence of low back pain(LBP) in drivers who work at high altitude, in order
      to seek the effective measures for prevention and treatment of LBP. METHOD: The
      spectral electromyographic(EMG) changes during isometric contraction of erector
      spinalis to fatigue in 26 drivers in the field were consecutively recorded after
      daily driving for 5 days. The relationship between the decline of median
      frequency and the development of the back extensor fatigue were analyzed.
      RESULTS: The decline rates of EMG median frequency of the erector spinalis on 1-5
      working day [(-0.258 +/- 0.087), (-0.248 +/- 0.070), (-0.256 +/- 0.097), (-0.267
      +/- 0.093), (-0.274 +/- 0.081)%/s respectively] were significantly different from
      that of baseline measured before work [(-0.175 +/- 0.114)%/s, P < 0.05 or P <
      0.01]. A positive correlation was also found between the decline rate and the
      working time(r = -0.809, P < 0.05). CONCLUSION: The high prevalence of LBP in the
      drivers working at high altitude is due to acumulative fatigue of back extensor
      resulting from long-distance driving, lack of proper rest, decrease of muscle
      endurance and increase of liability to fatigue, consequently leading to the
      muscle dysfunction and finally LBP.

PMID- 14694603
TI  - [Lower back pain in truck drivers working in plateau areas and its prevention].
AB  - OBJECTIVE: To investigate the epidemiological characteristics of lower back pain
      of truck drivers in plateau areas with an analysis of the causes and evaluated
      the effects of the protective measures. METHODS: The self-reported lower back
      symptom was investigated by questionnaire in 1,132 male drivers in plateau areas.
      Vibration of the driver lumbar back was measured real time with or without
      wearing corset. Study the effect of the special corset for drivers and the
      massage on back by self-control design of big sample intervention experiments.
      RESULTS: The prevalence of lower back pain of drivers in plateau areas was 86.1%.
      High level of its prevalence is due to many factors. Special corset for drivers
      and massage on back by themselves can reduce the degree of the pain. CONCLUSION:
      Driving in plateau areas is a special occupational work with high level of
      prevalence of lower back pain which can be prevented.

PMID- 14694604
TI  - [Investigation on injury of liver and kidney among the workers exposed to
      terephthalic acid, ethylene glycol and(or) dowtherm A].
AB  - OBJECTIVE: To study injury of liver and kidney among the workers exposed to
      terephthalic acid(TPA), ethylene glycol(EG) and(or) dowtherm A(DOW), and research
      for early biological monitoring indexes. METHODS: By using the method of
      occupational epidemiology, an investigation of industrial hygiene in a chemical
      fibre corporation was carried out and the changes of the liver and kidney
      functions were analyzed among the workers who had been exposed to TPA, EG, DOW.
      RESULTS: The values of serum gamma-glutamyl traspetidase(GGT) and total bile
      acid(TBA) in TPA + EG + DOW group men were (35.45 +/- 16.09) U/L, (10.29 +/-
      6.76) mumol/L respectively and the values of serum alanine transaminase(ALT) and
      TBA in TPA + EG + DOW group women were(30.68 +/- 8.58) U/L, (9.53 +/- 6.63)
      mumol/L respectively, significantly higher than those in TPA, DOW and control
      groups(P < 0.05, P < 0.01). Compared with TPA, DOW and control groups, the values
      of urine N-acetyl-beta-D-glucosaminidase(NAG) and beta 2-2-microglobulim (beta 2
      MG) in TPA + EG + DOW group of both men and women increased significantly(P <
      0.05, P < 0.01), with(5.68 +/- 4.01) U/mmol Cr and (23.49 +/- 13.44) mg/mol Cr,
      and(6.68 +/- 4.68) U/mmol Cr and (22.80 +/- 13.00) mg/mol Cr, respectively.
      Analysis of regression indicated that both liver and renal injuries of the
      workers were evidently correlated with their exposure to TPA, EG and DOW after
      adjustment for the confounding factors such as sex, smoking, drinking, etc(P <
      0.001). CONCLUSION: Based on available knowledge, it is reasonable to assume that
      the joint actions should be considered on the injury of liver and kidney caused
      by TPA, EG and(or) DOW among the workers. Serum ALT, GGT, TBA, urine NAG and beta
      2-MG should be suggested as biomarkers for liver and kidney damage.

PMID- 14694605
TI  - [Study on vertebral degenerations of coal miners with low back pain by means of
      computerized tomography].
AB  - OBJECTIVE: To study lumbar vertebral degenerations of coal miners with low back
      pain. METHODS: 40 underground miners with low back pain, aged from 30 to 50 years
      and employed for a length from 10 to 30 years, were taken as observation group.
      30 ground workers without low back pain but with almost the same age, employment
      length and height etc. were selected as control group. Intervertebral discs at
      L3/L4, L4/L5, L5/S1 were scanned with computerized tomography, comparing
      herniated discs, sagittal diameter of vertebral canal, height of lateral recess,
      vertebral hypertostosis, ligament hypertrophy and calcification between two
      groups. RESULTS: L3/L4, L4/L5, L5/S1 herniated discs and narrow lateral recess in
      observation group(0.33 +/- 0.15, 0.53 +/- 0.25, 0.45 +/- 0.18 and 0.40 +/- 0.08,
      0.31 +/- 0.05, 0.37 +/- 0.07) were more serious than that in control group(0.28
      +/- 0.11, 0.32 +/- 0.21, 0.37 +/- 0.19 and 0.42 +/- 0.10, 0.43 +/- 0.07, 0.40 +/-
      0.06), but only with significant difference at L4/L5 (P < 0.01). Sagittal
      diameter of vertebral canal in observation group is narrower than that in control
      group but of little significance(P > 0.05). Cases of vertebral hyperostosis,
      ligament hypertrophy and calcification were found more frequent in observation
      group(45.00%, 42.50%, 22.50%) than in control group(23.33%, 16.67%, 16.67%), but
      only ligament hypertrophy was remarkable(P < 0.05). CONCLUSIONS: As compared with
      control group lumbar vertebral degenerations are more serious in underground
      miners with manifestations like herniated disc and narrow lateral recess mainly
      at L4/L5.

PMID- 14694606
TI  - [Tumor necrosis factor and nitric oxide in the protective heat stress model].
AB  - OBJECTIVE: To investigate the variation and the effect of TNF and NO in the
      process of the creation of protective heat stress model and provide more
      thoretical basis. METHODS: The rats were properly treated with heat and then the
      serum was separated. Radioimmunoassay and nitrate reductase assay were employed
      to measure the concentration of TNF and NO at different time between 0 h and 24 h
      after heat stress respectively. RESULTS: Compared with the control, the
      concentration of TNF increased significantly 2 h, 4 h, 8 h, 12 h after heat
      stress, of which 2 h, 12 h(P < 0.05), 4 h, 8 h(P < 0.01), but no significant
      changes 0 h, 24 h after heat stress. The concentration reached the peak 4 h after
      heat stress[(3.35 +/- 0.20) ng/ml] and increased significantly than 0 h, 2 h, 8
      h, 12 h, 24 h after heat stress(P < 0.01, P < 0.05). 24 h after heat stress it
      recovered to normal standard. Compared with the control, the concentration of NO
      was higher 2 h, 4 h, 8 h, 12 h, 24 h after heat stress(P < 0.05), but no
      significance at 0 h. The concentration amounted to peak 8 h after heat
      stress[(108.21 +/- 27.89) mumol/L] and increased than 0 h, 2 h, 4 h after heat
      stress(P < 0.01). After 8 h it began to decrease continuously in heat stress
      group, however it was higher 24 h after heat stress than control. CONCLUSION: TNF
      and NO played an important role in the process of the creation of protective heat
      stress model.

PMID- 14694607
TI  - [Influence of anisodamine on heat-stress in rats].
AB  - OBJECTIVE: To study whether previously intravenous injection of anisodamine can
      prevent endotoxemia of heat stroke of rats. METHODS: Experimental animals were
      randomly divided into two groups, their average artery pressure, heart rate,
      survival time, survival rate and rectal temperature were measured at an
      environmental temperature of 38 degrees C-40 degrees C and 50%-60% retative
      humidity. Blood samples for endotoxins analyses were taken both before and after
      heat-stress. RESULTS: During heat stress, the animals of rectal temperature of
      the experimental and control groups continuously increased and two hours later,
      separately to (42.7 +/- 0.6) degree C and (43.1 +/- 0.5) degree C, without
      statistic difference(P > 0.05), and to (44.6 +/- 0.4) degree C and (44.2 +/- 0.3)
      degree C prior to death, with statistic difference(P < 0.05). Before the
      experiment, the contents of endotoxins of portal vein blood were (45.7 +/- 5.2)
      pg/ml and (42.6 +/- 5.4) pg/ml, and that of systemic blood was (14.8 +/- 4.5)
      pg/ml and (13.9 +/- 7.2) pg/ml, without statistic difference(P > 0.05). Two hours
      later, the contents of portal vein blood separately increased to (122.2 +/- 16.7)
      pg/ml and (49.7 +/- 10.2) pg/ml, obviously higher than that before heat-stress(P
      < 0.01). And there were clear statistic difference between the two groups(P <
      0.01). The changing tendency of the heart rhythm is almost the same in two
      groups, that is, first rose and then fell. But it is without statistic difference
      before and two hours later(P > 0.05): before heat-stress, the average artery
      pressures were (13.3 +/- 0.6) kPa and (13.6 +/- 0.5) kPa, without statistic
      difference(P > 0.05), and two hours later, were (9.6 +/- 0.5) kPa and (8.6 +/-
      0.6) kPa, with obvious statistic difference(P < 0.01). The survival time of the
      animals were (166.5 +/- 16.9) min and (144.5 +/- 18.2) min with obvious statistic
      difference(P < 0.01), the survival rate of heat stressed rats in the experimental
      group were obviously higher than control group(P < 0.01 or P < 0.05).
      CONCLUSIONS: Anisodamine can prevent endotoxemia in rats suffering heat stroke.

PMID- 14694608
TI  - [Hygienic investigation of indoor environment in air-conditioned passenger
      trains].
AB  - OBJECTIVE: Explore the hygienic status of indoor environment in railway air
      conditioned passenger trains. METHODS: We carried out a hygienic investigation of
      various air-conditioned passenger trains on total 10 railway lines in Shanghai,
      Chengtu, Kunming, Harbin, Urumchi and Guangzhou railway bureaus for two years
      between July, 1997 and Oct., 1999. The monitoring was conducted on difference
      train cars at different time, different railway status. The control groups were
      selected in the same condition. RESULTS: The results of temperature and wind
      speed in air-conditioned trains both meet with the national standards GB 9673
      1996 in summer and winter. The humidity in summer exceeded the national
      standards. Of different railways the status, the noise in four different cars
      except dining cars exceeded the national standards. The results of shock
      demonstrated that all measure up to the standards of ISO 2631/1-85. As to indoor
      air quality, the concentration of CO in air-conditioned trains in difference
      seasons(summer, autumn, winter) all met with the national standards, the ratio
      was 100%. In summer, the concentrations of CO2 in hard seat cars and soft berth
      car exceeded the national standard with a statistic significance(P < 0.01). In
      winter, the concentrations of CO2 in soft berth and hard berth cars both exceeded
      the same standard. The results of inhalable particulate matter(IP) and total
      count of bacteria all satisfied the standards, meanwhile the natural lighting and
      artificial illumination in air-conditioned train cars all were superior to that
      in ordinary trains. CONCLUSION: Humidity in summer and noise in dining car
      exceeded the standards, the concentration of CO2 in different cars in summer and
      winter exceeded the standards in some degrees.

PMID- 14694609
TI  - [Study on the relationship between occupational stress and psychological health
      state among oil workers].
AB  - OBJECTIVE: To study the relationship between occupational stress and
      psychological health state among oil workers. METHODS: 1,230 oil workers in 122
      work types of oil industry were selected and written occupational stress
      questionary(OSQ) and symptom check list (SCL-90). RESULTS: Petroleum workers'
      psychological health states were poor with increasing occupational stress degree.
      The scores in physical symptoms(1.87 +/- 0.80, 1.72 +/- 0.70), depression(1.74 +/
      0.76, 1.62 +/- 0.67), horror(1.48 +/- 0.65, 1.39 +/- 0.55) in the high and
      medium stress group were obviously higher than those in low stress group(1.55 +/-
      0.61, 1.43 +/- 0.54, 1.28 +/- 0.46, respectively, P < 0.05). The score of mood
      state in the high and medium stress group was obviously higher than that in low
      stress group(P < 0.05). Psychological health states and mood state in the
      petroleum workers with short service length are significantly poorer than that
      with long service length(P < 0.01). CONCLUSION: Occupational stress should affect
      psychological health state of petroleum workers.

PMID- 14694610
TI  - [A clinical study on delayed encephalopathy after carbon monoxide poisoning].
AB  - OBJECTIVE: To investigate clinical and imaging characteristics of delayed
      encephalopathy after carbon monoxide poisoning(DEACMP). METHODS: A retrospective
      and comparative analysis of neurological manifestations, course, periods of false
      cure, prognosis and neuroimaging findings were conducted in 198 patients with
      DEACMP. RESULTS: Of these patients, 60.1% obtained an initial recovery within 30
      d, 23.7% within 31-60 d and 14.6% over 60 d. Total clinical rate was 32.8%, and
      effectiveness rate 70.1%. According to imaging findings, 15.2% patients were
      found to have bilateral lesions of basal ganglion, and 70.0% with lesions of
      subcortical white matter, 12.6% with lesions of two types above mentioned and
      2.1% with no lesions. The intervals between onset of illness and initial recovery
      were (44.6 +/- 10.1), (38.2 +/- 11.9), (61.3 +/- 17.0) d, and (7.5 +/- 2.4) d
      respectively. Imaging findings can demonstrate the severity of brain injury, but
      not necessarily parallel to the improvement of illness, for which SPECT proves
      more useful. CONCLUSIONS: DEACMP is involved in ischemic brain injury and a self
      limited illness.

PMID- 14694611
TI  - [The changes of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha(6-keto
      PGF1 alpha) in the lungs of rats drowned in hypothermic-sea-water].
AB  - OBJECTIVE: To observe changes of thromboxane B2 (TXB2), 6-keto-prostaglandin F1
      alpha(6-Keto-PGF1 alpha) and TXB2/6-Keto-PGF1 alpha (T/P) in lungs of rats
      drowned in hypothermic sea water and to assess their influence on the blood-gas.
      METHODS: Rats of different groups were drowned nearly to death in hypothermic sea
      water and then taken out of the water rapidly, observed at room temperature,
      after that the following steps were taken in 5, 15, 30, 60, 240 min and 360 min
      groups, that were 1 ml arterial blood taken from left heart for blood-gas
      analysis including pH, PaO2 and PaCO2, rectal temperature observed; at last, the
      ratio of left dry lungs with left wet lungs was assessed, TXB2 and 6-Keto-PGF1
      alpha in right lungs were examined in all above groups and dead group(14 rats
      dead, only 4 examined). RESULTS: The rectal temperature[(20.13 +/- 0.48) degree
      C], pH(6.68 +/- 0.03), PaO2[(45.00 +/- 6.30) mm Hg)], TXB2[(97.46 +/- 17.46)
      ng/L] and 6-Keto-PGF1 alpha[(25.59 +/- 8.12) ng/L] dropped to the lowest point in
      the 5 minutes group(P < 0.01), while PaCO2[(89.18 +/- 5.10) mm Hg] reached the
      highest point(P < 0.01), all above items from 5 minutes group then showed a
      recovering tendency, but only the pH in 240 minutes and 360 minutes groups as
      well as TXB2 in 360 minutes group and dead group reached near the level of normal
      control groups (P > 0.05); T/P had a rising tendency and reached the highest
      point in the 360 minutes group. CONCLUSIONS: The production and secretion of TXB2
      and 6-Keto-PGF1 alpha were influenced by hypothermia, hypoxemia and acidosis, the
      imbalance of T/P could be one of factors influencing the improvement of blood gas
      index.

PMID- 14694612
TI  - [Study on occupational respiratory diseases in fur-processing workers].
AB  - OBJECTIVE: To study the respiratory system injury in fur processing environment.
      METHODS: Environmental fungal survey was conducted in the fur processing
      procedures. Investigation of respiratory symptoms and chest X-ray examination
      were also carried out in 138 fur processing workers and 40 control workers. At
      the same time, the serum antibodies to fungi were analyzed by ELISA. RESULTS:
      Fungal number(629-3,681 cfu/m3) in fur processing procedures was much higher than
      those in the control environment. Cladosporium and Alternaria were the leading
      strains of fungi in fur processing procedures. The rates of respiratory
      symptoms(cough, sputum, chest tightness, dyspnea, and fever) in fur processing
      workers were higher than those in the control workers. The rates of the symptoms
      in female workers were 37.9%, 28.4%, 10.5%, 22.1%, 4.2%, respectively.
      Abnormalities of chest X ray were found in 7 workers. The serum antibodies to
      Cladosporium and Alternaria(A450 nm 0.631, 0.724, respectively) in fur workers
      were significantly higher than those in the control workers(P < 0.05). The
      positive rates of the antibodies to Cladosporium and Alternaria(44.2%, 42.8%)
      were significantly higher than those in the control workers(P < 0.01).
      CONCLUSION: Cladosporium and Alternaria may be the pathogens of occupational
      respiratory diseases in fur processing workers.

PMID- 14694613
TI  - [Measurement of alveolar surfactant after bleomycin-induced pulmonary injuries].
AB  - OBJECTIVE: To observe the ultrastructures of rat alveolar type II cells and
      change of composition of phospholipid(PL) and content of protein in pulmonary
      surfactant(PS), to investigate the relation between change in composition of PL
      and activity of alveolar type II cells. METHODS: The rats lung injury models were
      made by intratracheally instilling bleomycin(BLM) (4 mg/ml, 5 mg/kg). 28 rats
      were divided into four groups: 3-day group, 7-day group, 14-day group and 28-day
      group. Preparations of each group were stained histochemically and examined by
      electron microscope, content of PL in BALF, composition of PL and content of
      protein of each group were determined respectively. RESULTS: (1) Rats lungs in
      experimental groups were found that PS lost continuously, appeared homogenous and
      chorionic, dropped in the pulmonary alveolies. 3-day group was more apparent.
      Ruthenium red attaching on pulmonary surfactant was thicker in 3-day group, and
      the colour deeper, no difference in 7-day group and 14-day group, thinner in 28
      day group. Content of PL in PS of BALF was increasing. Content of
      phosphatidylglycerol(PG) increased in 3-day group, decreased in 7-day, 14-day and
      28-day group. The change of content of phosphatidylinositol(PI) was reversed. (2)
      Alveolar type II cells degenerated, necrotized, even disintegrated in 3-day group
      and 7-day group. 3-day group was more apparent. Proliferations of alveolar type
      II cells were found in each group, 7-day group was more apparent. We found that
      type II cells transformed to type I cells in 14-day group, extended and attached
      on bare basement membrane. Content of protein in PS was the highest in 3-day
      group, almost equal to the content of the control group in 28-day group.
      CONCLUSION: Morphologic change and alternation of quality and quantity of PS
      after bleomycin-induced pulmonary injures specifically reflect the activity of
      alveolar type II cells. Measuring content of PL in BALF is one of simple and
      feasible method judging activity of alveolar type II cells when lungs of the rats
      are injured early by bleomycin.

PMID- 14694614
TI  - [Study on the relationship between glutathione S transferase mu gene deletion and
      leukemia in workers exposed to benzene].
AB  - OBJECTIVE: To study the relationship between glutathione S transferase M1(GST mu)
      gene deletion and leukemia in workers exposed to benzene. METHODS: A matched
      population-based case-control survey with multivariate Logistic regression
      analysis was conducted in this study. RESULTS: In the population of 34 patients
      and their matched controls, the absence of the GST mu genotype conferred odds
      ratio of 3.6. It suggested that GST mu was an important determinant of
      heterogeneity in individual susceptibility to leukemia associated with exposure
      to benzene. The single-variance analysis indicated that these markedly
      significant factors were GST mu gene deletion, GST mu isoenzyme activity,
      duration of exposure, GST isoenzyme activity, smoking quantity and average
      concentration of benzene in workshop air. The multivariate analysis indicated
      that these markedly significant factors were GST mu gene deletion, duration of
      exposure to benzene and GST mu isoenzyme activity. CONCLUSION: GST mu gene
      deletion may be associated with increased risk of leukemia in workers exposed to
      benzene and is one of genetically determined factors.

PMID- 14694615
TI  - [Study on the relationship between the opacity of lens and the levels of 2, 6
      dinitro-4-amino-toluene (DNAT) in the urine of workers exposed to
      trinitrotoluene(TNT)].
AB  - OBJECTIVE: To find out the relationship between the opacity in lens and the
      contents of 2,6-dinitro-4-amino-toluene(DNAT) in the urine of exposed workers.
      METHODS: Testing the exposed worker's lens and measuring the contents of DNAT in
      the urine after work. RESULTS: When the opacity of the lens occurred, the
      contents of DNAT in the urine(2.38 mg/L) of workers exposed to TNT were
      significantly higher than those without opacity in lens(1.44 mg/L) (P < 0.05).
      CONCLUSION: The severity of opacity of lens increased with the contents of DNAT
      raised in the urine. The threshold value suggested by ILO is not applicable to
      Chinese occupational population, which recommends the contents of DNAT(30 mg/L)
      in the urine for the workers exposed to TNT as biological occupational exposed
      limits.

PMID- 14694616
TI  - [Study on the prevention, control and elimination of pneumoconiosis in fluorite
      mine].
AB  - OBJECTIVE: To prevent pneumoconiosis by strengthening comprehensive dust-proof
      and controlling its pathogenesis, and to discuss feasibility of pneumoconiosis
      elimination in our country. METHODS: Comprehensive dust-proof was used for
      reducing the concentration of dust. Epidemiological investigation of
      pneumoconiosis was employed for evaluating the efficiency of pneumoconiosis
      prevention. Prospective tracking investigation was used for identifying the
      feasibility of the pneumoconiosis elimination. RESULTS: The outcomes of dynamic
      observation of 35 years from 1962 to 1996 and results of prospective thirty years
      tracking investigation showed that after comprehensive dustp-roof, the average
      dust concentration and time weighted mean dust concentration in workers'
      operating conditions decreased from 366.0 mg/m3 and 163.4 mg/m3 to 1.2 mg/m3 and
      1.3 mg/m3 respectively, and the declined rates reached 99.7% and 92.1%,
      respectively. After controlling pneumoconiosis pathogensis, the incidence rate of
      pneumoconiosis, its prevalence rate and mortality rate decreased from 24.8%,
      85.5% and 5.9% to zero respectively. CONCLUSION: The thirty years prospective
      tracking investigation validated that the incidence of pneumoconiosis was zero.
      So the goal to eliminate pneumoconiosis was achieved.

PMID- 14694617
TI  - [Risk factors for malignant pleural mesothelioma in crocidolite contaminated
      area].
AB  - OBJECTIVE: To explore the risk factors for mesothelioma so as to provide
      epidemiological evidences for prevention of this disease and for further study of
      its pathogenesis. METHODS: A 1:1 paired case-control study was carried out in
      which asbestos exposure, life style and histories of cancer in first-degree
      relatives of 23 patients who had mesothelioma were compared with those of
      controls. RESULTS: The mean age of patients was 57.96 years with a latency period
      of 52 years. There were no significant differences in mean exposure age, mean
      exposure periods, and smoking, drinking habits between patients and controls. The
      mean cumulative exposure of patients was 37.2 x 10(5) f, which was significantly
      higher than that of controls (32.3 x 10(5) f, P = 0.005). The odds ratio
      increased with the cumulative exposure. The percentage of cancer in first-degree
      relative of patients (26.1%) was significantly higher than that of controls
      [(4.4%, P < 0.05), OR = 7.75 (95% CI: 0.85-71.43)]. CONCLUSION: There may be a
      dose-response relationship between mesothelioma and asbestos exposure. A family
      history of cancer may be a risk factor for mesothelioma, or may indicate an
      increased susceptibility to mesothelioma under the same level of asbestos
      exposure.

PMID- 14694618
TI  - [Effects of rush-mat dust on the health of exposed workers].
AB  - OBJECTIVE: To evaluate the effect of exposure to rush-mat dust on the health of
      workers. METHODS: A cross sectional study of 661 workers (349 men, 312 women)
      from 35 rush-mat plants was carried out by using occupational health
      investigation, questionnare and physical examination. RESULTS: The geometric mean
      total dust concentration in the workshop was up to 20.00 mg/m3, and the geometric
      mean respirable dust concentration reached 8.22 mg/m3. The mean free SiO2
      concentration of accumulated dust was 25.6%. The prevalence of radiographic small
      opacities profusion category > or = 1/0, according to the China Classification
      for pneumoconiosis (GB 5906-2000), and compared with the ILO 1980 system, was
      2.57%. Even more, one man had category 2 pneumoconiosis with progressive massive
      fibrosis. However, the incidence of pneumoconiosis (1/0 at least) was correlated
      with work duration and dust concentration(r = 1.156, P < 0.001; r = 0.106, P =
      0.006, respectively). Some positive correlations were found between the incidence
      of cough or expectoration and occupational exposure (r = 0.085, P = 0.028; r =
      0.094, P = 0.016, respectively). CONCLUSION: To our knowledge, this is the first
      report of rush pneumoconiosis in China. The results have offered the possibility
      of a dose-response relationship between rush-mat dust and pneumoconiosis. More
      investigation in this area is need.

PMID- 14694619
TI  - [The relationship between silicosis and the polymorphism of HLA-DRB1 *, DQB1 *
      genes].
AB  - OBJECTIVE: To investigate the relation between the susceptibility to silicosis
      and the polymorphism of HLA-DRB1 *, DQB1 * genes in Chinese Hans. METHODS: HLA
      DRB1 * and DQB1 * gene polymorphism were tested in 48 silicosis patients and 100
      normal controls by using polymerase chain reaction of sequence-specific primers
      (PCR-SSP). RESULTS: The allele frequencies of DRB1 * 1401 and DQB1 * 05 in
      silicosis patients were significantly higher than those in normal controls (chi 2
      = 5.61, P = 0.0066, RR = 17.40; chi 2 = 10.70, P = 0.0011, RR = 3.81,
      respectively), while the allele frequency of DRB1 * 09 was significantly lower in
      silicosis patients than that in controls (chi 2 = 5.70, P = 0.0187, RR = 0.21).
      There was a significant difference between the patient group and control group.
      CONCLUSION: HLA-DRB1 * 1401 and DQB1 * 05 may be the susceptible genes and HLA
      DRB1 * 09 the protection gene of silicosis, both susceptibility and protection
      may be related to HLA-DR gene locus. The joint action of allele genes may affect
      the pathogenesis of silicosis.

PMID- 14694620
TI  - [The relationship between glutathione S-transferase M1 genotypes and lipid
      peroxidation in asbestos workers].
AB  - OBJECTIVE: To study the relationship between glutathione S-transferase M1 (GSTM1)
      genotypes and lipid peroxidation of asbestos workers. METHODS: 94 asbestos
      workers and 51 controls were selected as subjects. The general information,
      occupational history and individual habits were collected by questionnaires in
      all participants. The venous blood was sampled and the plasma was separated for
      the detection of malondialdehyde (MDA) level and lymphocytes for DNA isolation
      and GSTM1 genotyping. RESULTS: MDA level was significantly higher in asbestos
      workers [(0.283 +/- 0.054) nmol/L] than that in controls [(0.163 +/- 0.053)
      nmol/L, P < 0.01], however, neither duration of exposure nor accumulated asbestos
      exposure dose was related to MDA levels; MDA levels in control workers with GSTM1
      +/- genotype [(0.190 +/- 0.034) nmol/L] were significantly higher than that in
      control workers with GSTM1 +/+ genotype [(0.138 +/- 0.055) nmol/L, P < 0.01].
      Among asbestos workers, the same trend could be found, but the differences was
      not significant(P > 0.05). When the workers were stratified by duration of
      exposure or accumulated asbestos exposure dose, MDA levels in individuals with
      GSTM1 -/- genotype were also higher than those with GSTM1 +/+ genotype, but the
      differences were also not significant(P > 0.05). CONCLUSION: Both exposure to
      asbestos and deficiency of GSTM1 genotype were related to lipid peroxidation in
      workers, but the role of the former may be more important than that of the
      latter.

PMID- 14694622
TI  - [Pathological observation on five autopsies of the alumina pneumoconiosis].
AB  - OBJECTIVE: To study the pathological characteristics and the morphological
      changes of alumina pneumoconiosis. METHODS: The pathological observation and
      analysis were performed in lungs of five autopsies with alumina pneumoconiosis.
      RESULTS: The early common pathological change of alumina pneumoconiosis was the
      dust spots. The dust fibrosis had two forms, one was the non-focal fibrous
      proliferation of interstitial space, the other was the proliferation of inner
      dust-spot fibrosis that finally developed into non-typical pneumoconiosis
      nodules. CONCLUSION: The pathological characteristics of the alumina
      pneumoconiosis may not be all the same to those of aluminium and aluminium oxide
      pneumoconiosis. Alumina pneumoconiosis is a complex pneumoconiosis. The typical
      pathological changes are the dust-spot emphysema and dust fibrosis of
      interstitial tissue. Infection in lung and complication of lung tumor, especially
      pneumo-tubercolosis would promote dust fibrosis. The pleural thickening, the
      relationship between lung cancer and alumina dust should be taken seriously.

PMID- 14694621
TI  - [Study on drug-resistance of Mycobacterium tuberculosis isolated from coal
      workers with silico-tuberculosis].
AB  - OBJECTIVE: To study the gene mutation and streptomycin, isoniazid or rifampicin
      resistance of Mycobacterium isolated from silico-tuberculosis patient's sputum so
      as to find a more effective therapy for this disease. METHODS: Mycobacteria
      tuberculosis were separated from 96 coal worker with silico-tuberculosis firstly.
      Then rpsL, KatG and rpoB fragments of genome were copied with PCR and compared
      their SSCP profiles with standard strains. RESULTS: 67 strains of streptomycin,
      isoniazid or rifampicin resistant Mycobacteria tuberculosis were found in routine
      drug resistance test, with the percentages of 80.5% (54/67), 58.2% (39/67)
      respectively. PCR-SSCP showed that out of 67 drug-resistant strains, 66(98.5%) of
      rpsL, 47(70.1%) of rpoB and 42(62.7%) of KatG appeared abnormal. CONCLUSION: Most
      of the resistant strains appeared gene mutation. The mution rates were higher
      than the results from routine drug resistance test.

PMID- 14694623
TI  - [Spirometrically controlled quantitative CT for detection of pulmonary function
      in silica-exposed workers].
AB  - OBJECTIVE: To evaluate the diagnostic value of spirometrically controlled
      quantitative CT in silica-exposed workers. METHODS: Whole lung spiral scans at
      50% vital capacity (VC) and image with high resolution CT(HRCT) at 10% VC and 90%
      VC level and 5 cm above/below carina were performed in 62 silica-exposed workers
      and 54 healthy adults. Automatic evaluation software, Pulmo, was used to evaluate
      the quantitative parameters and compared with clinical pulmonary function tests.
      RESULTS: 9 workers with emphysema were detected by CT scans from 62 silica
      exposed workers. The quantitative parameters of 10% VC and 90% VC were
      significantly different between the silica-exposed workers and the controls (P <
      0.05). With the increasing of length of exposure to silica dust, the difference
      showed a ladder-like rising. CONCLUSION: Spirometrically controlled quantitative
      CT is a sensitive, accurate and objective method. It is superior to conventional
      CT and pulmonary function tests for the early detection in silica-exposed
      workers, espicially for detecting early stage of small airway disease.

PMID- 14694624
TI  - [Application value of measurement of the regional pulmonary ventilation by
      electric impedance pneumograph in the clinical diagnosis of pneumoconiosis].
AB  - OBJECTIVE: To study the value of clinical application and distribution character
      of regional pulmonary ventilation of patients with various type of
      pneumoconiosis. METHODS: 132 patients with various type of pneumoconiosis were
      observed by electric impedance pneumograph(EIPV) and routine lung function test.
      The results were compared with the measured value of 100 healthy cases. RESULTS:
      The regional pulmonary ventilation of the three kinds of pneumoconiosis(founder's
      pneumoconiosis, silicosis and asbestosis) was increased in both side of upper
      pulmonary region and decreased in both of lower pulmonary region. The ventilation
      distribution showed that the right pulmonary ventilation increased predominantly,
      accounted for 53.03% (70/132) of total lung ventilation. There was significant
      difference(P < 0.01) compared with the normal healthy men's EIPV, but no
      difference(P > 0.05) among various type of pneumoconiosis. There was also no
      difference(P > 0.05) between pneumoconiosis patients with normal ventilation
      function and various type of ventilation obstacle of pneumoconiosis. One
      silicosis patient complicated by atelectasis of the left upper lobe, another
      silicosis patient complicated by lung cancer and their EIPV accorded with their
      chest X-rays. CONCLUSION: EIPV could not be measured by routine lung function
      test. It may be the supplement to latter parameter and as a substitute for radio
      imaging of pulmonary ventilation in pneumoconiosis complicated by other regional
      pulmonary disorder.

PMID- 14694625
TI  - [CT quantitative study of coal miner's pneumoconiosis].
AB  - OBJECTIVE: To study the value of CT quantitativeness in the diagnosis of coal
      miner's pneumoconiosis. METHODS: 104 cases were examined by HRCT scan at top of
      aortic arc, carina of trachea, 3 cm below the bifurcation of bronchi, among them
      there were 87 patients with different stages of coal miner's pneumoconiosis, 17
      cases of normal males as the control group. All images were determined by CT
      density histogram at specific region (- 1,024-0 HU). Calculated the percentage of
      each pixel included a varying number of CT value, and the ratio of density values
      in the specific region. RESULTS: The ratio of density values in the region of 
      983 (-) -778 HU was 87.31% in normal control group, and 80.51%, 75.27% and 72.99%
      respectively in the I, II, III stages of coal miner's pneumoconiosis. There were
      statistically significant differences among the groups (P < 0.01). CONCLUSION: CT
      quantitative histogram information was able to observe the fibrosis and its
      degree of coal miner's pneumoconiosis. It has a good diagnostic value for its
      reliability and objectiveness.

PMID- 14694626
TI  - [The model of mouse lung tumor short-term induction test for assaying the
      carcinogencity induced by extracts of birch wood dust].
AB  - OBJECTIVE: To assay the carcinogencity of water and organic extracts of birch
      wood dust. METHODS: One stage and two stage model of mouse lung tumor by short
      term induction test were used. RESULTS: In the one stage experiment, no
      significant difference of the incidence of mice lung tumors was observed between
      different dosage groups of water extracts and organic extracts. In the two stage
      experiment, the tumor incidence and the average number of tumor per mouse in
      three dosage groups treated with the water extracts(1, 2, 4 g/kg) were 4.08% and
      0.04, 8.33% and 0.15, 14.30% and 0.24 respectively with dose increment. There was
      a significant dose-response relationship between them(P < 0.05), and the tumor
      incidence and the average number of tumor per mouse in 4 g/kg group were
      significantly higher than those in the control group and 1 g/kg group and its one
      stage group(P < 0.05). The tumor incidence and the average number of tumor per
      mouse induced by organic extracts were higher with increasing dose, but no
      significant difference among groups was found (P > 0.05). CONCLUSION: Both
      extracts of birch wood dust may be initiators, and carcinogenic effect of the
      water extract is stronger than that of the organic extract.

PMID- 14694627
TI  - [Study on hereditary toxicity of bass wood dust].
AB  - OBJECTIVE: To explore the genotoxicity of bass wood dust. METHODS: Micronucleus
      frequency in peripheral lymphocytes of workers exposed to bass wood dust in a
      match factory were examined, solution of bass wood dust emmersion was prepared
      and the effect on micronucleus frequency in poly-dyeing red blood cell of mice's
      sternum marrow was also detected. Single cell gel electrophoresis assay was used
      to detect DNA damage in liver cell, the level of oxygen free radical, lipid
      peroxidation(MDA) in the liver and the activity of superoxide dismutase(SOD) in
      red blood cells were also studied. RESULTS: The positive frequency of
      micronucleus in bass wood-exposed workers with different length of service (0-, 5
      , > or = 10 a) were 50.0%, 51.9%, 50.0% respectively, significantly higher (P <
      0.01) than that of the control group(4.5%). A dose-effect relationship could also
      be found in the mice's micronucleus frequency study(r = 0.78, P < 0.01). The
      activities of SOD[(10.98 +/- 5.74), (15.70 +/- 7.54), (29.63 +/- 14.97)
      microgram/g Hb] were significantly lower than that of control group[(35.80 +/-
      12.92) microgram/g Hb], and the level of MDA[(4.93 +/- 0.90), (4.61 +/- 1.06),
      (4.33 +/- 0.69) mmol/g liver] were significantly higher than that of the control
      group[(2.51 +/- 0.34) mmol/g liver]. Single cell gel electrophoresis study showed
      DNA strand breaks increased with the dose increase and the level of oxygen free
      radical also increased with the dose increase. CONCLUSION: Bass wood dust may
      have certain degree of genotoxicity.

PMID- 14694628
TI  - [Downregulation of gap junctional intercellular communication induced by silicon
      dioxide in the pulmonary alveolar epithelial cell].
AB  - OBJECTIVE: To explore the effect of silica dioxide(SiO2) on proliferation and
      downregulation of gap junctional intercellular communication (GJIC) in pulmonary
      alveolar epithelial cells (CCL-64 cells). METHODS: The pulmonary alveolar
      macrophages(PAMs) were incubated in the serum-free RPMI 1640 containing the
      various concentration of SiO2 for 24 hours. The supernatants were prepared and
      added 5% (V/V) into 2% (V/V) NBS RPMI 1640 to stimulate the proliferation of CCL
      64 cells for 24 hours. A set of "blank control", run in parallel, contained RPMI
      1640 + 2% (V/V) NBS alone. The proliferation of CCL-64 cells was detected using
      MTT assay(to show as the absorbency, A570nm). GJIC function was measured using
      the fluorescence redistribution after photobleaching(FRAP) assay [to express as
      the transfer rate of the fluorescence, K (x 10(-3)/s)], with a laser scanning
      confocal microscope(LSCM, Leica TCS SP). RESULTS: The silica-exposed PAM
      supernatants could induce both the proliferation(F = 9.679, P < 0.01) and
      downregulation of GJIC(F = 20.587, P < 0.01) of CCL-64 cells. In the range of 50
      500 micrograms/ml SiO2 concentrations, the proliferation (A570nm values) and
      GJIC(the transfer rate, K) were fitted well in a dose-dependent
      manner(proliferation: r = 0.891, P < 0.05; GJIC: r = -0.943, P < 0.05).
      CONCLUSION: By way of stimulating the PAM, SiO2 could inhibit GJIC function in
      lung alveolar epithelial cells, and induce epithelial cell proliferation. In the
      pathogenesis of silicosis, the downregulation of GJIC of the pulmonary epithelial
      cells may play an important role in silica-mediated alveolar epithelial cell
      injury.

PMID- 14694629
TI  - [Stimulation single fiber electromyography in rats with myasthenia induced by
      organophosphorus insecticides and their mixtures poisoning].
AB  - OBJECTIVE: To study the neuromuscular function and its relation with the
      occurrence of myasthenia in rats poisoned by dimethoate (D), phoxim (P), methomyl
      (M), M + D and M + P respectively. METHODS: The stimulation single fiber
      electromyography(SSFEMG) at different stimulus frequencies(5, 10 and 20 Hz) was
      used. The whole blood cholinesterase (ChE) activity was measured 1 h before and
      after poisoning. RESULTS: (1) Myasthenia occurred in 5 out of 9.5 out of 10.5 out
      of 5, and 8 rats poisoned by D, P, M + D, and M + P, respectively. (2) The
      average mean consecutive differences(MCD) at 5, 10, and 20 Hz in myasthenic rats
      were significantly higher than those of poisoned rats without myasthenia and the
      control ones. (3) SSFEMG changes at 5, 10 and 20 Hz were significantly consistent
      with the clinical manifestation of myasthenia, especially at 10 Hz and 20 Hz. (4)
      ChE activity was significantly lower in rats with P or D poisoning while ChE
      inhibition was of no difference in rats with M, M + D, and M + P poisoning. In
      the D poisoning and P poisoning groups, there was no significant difference in
      ChE inhibition between the rats with and without myasthenia. CONCLUSION: Muscle
      weakness was associated with neuromuscular transmission dysfunction, but not well
      correlated with ChE inhibition. The SSFEMG with stimulus frequency at 10 Hz or 20
      Hz could be used to detect the neuromuscular dysfunction during myasthenia
      induced by organophosphate insecticides and their mixtures poisoning.

PMID- 14694630
TI  - [Study on silica induced DNA damage and its influence factor].
AB  - OBJECTIVE: To detect DNA damage in Chinese Hamster Lung Fibroblast(CHLF) exposed
      to low doses of silica particles(7.5 - 120.0 micrograms/ml). METHODS: Comet assay
      was used to detect DNA damage. The cells were divided into various groups by
      doses and incubation time of silica particles to observe silica-induced DNA
      damage; and the influence of hydroxyl radicals and calcium ion in DNA damage by
      using deferoxamine and verapamil was also studied. The tail lengths of comet were
      used to measure DNA damage. RESULTS: The tail lengths were significantly longer
      in exposed cells, compared to matched controls(P < 0.01), and were increased in a
      dose-dependent manner from 7.5-120.0 micrograms/ml. The tail lengths of two-hour
      group were longer than one-hour group. When exposed to 90 micrograms/ml silica
      particles, 0.5-2.0 mmol/L deferoxamine and 2.5-20.0 micrograms/ml verapamil could
      attenuate silica-induced DNA damage effectively, their protective effects were
      increased in a concentration-dependent manner. CONCLUSION: Small dose of SiO2
      could induce CHLF DNA damage. Calcium ion and hydroxyl radical may take part in
      this process, antioxidant and calcium antagonate may protect SiO2 induced DNA
      damage.

PMID- 14694631
TI  - [Study on making pneumoconiosis model and method of lung lavage in rabbit].
AB  - OBJECTIVE: To provide an intact rabbit pneumoconiosis model and a method of lung
      lavage for studying the pathogenesis and treatment of pneumoconiosis. METHODS:
      The dust particles(< or = 5 microns diameter) were poured into the trachea of
      rabbit by trachea spile. The lung lavage of rabbit was carried out by the
      improved trachea catheter method. RESULTS: The rabbit lungs exposed to coal dust
      showed many black dust spots and there were proliferation of fibroblasts. The
      rabbit lungs exposed to silica dust showed nodules and several fusing nodules.
      The X-ray film showed that there were small irregular shadows, or fusing together
      into flake-like or round shadows in both lungs. The recovery rate of the lung
      lavage was 89%-94%. CONCLUSION: The model made by trachea spile and the method of
      lung lavage by the improved trachea catheter were simple, safe and without being
      injured.

PMID- 14694632
TI  - [Effects of pyrethroids on the concentrations of thyroid hormones in the rat
      serum and brain].
AB  - OBJECTIVE: To investigate the effects of pyrethroids on the concentrations of
      thyroid hormone in rat brain. METHOD: Permethrin (PM) and deltamethrin (DM) were
      administered to the rats with daily doses of 100, 200 and 400 mg.kg-1.d-1 and
      6.25, 12.5 and 25 mg.kg-1.d-1, respectivelly for 15 days. Serum and brain tissue
      determinations of thyroxin (T4) and triiodothyronine (T3) were performed by
      radioimmunoassay (RIA). RESULTS: PM induced a dose dependent decrease in the
      serum levels of T4, T3, fT4 and fT3 and an increase in the serum TSH levels,
      whereas DM was only able to induce a dose dependent decrease in the serum levels
      of T4. PM treatment reduced both the levels of T4 and T3 in homogenates of the
      cerebral cortex and hippocampus respectively, whereas the highest dose of DM
      decreased only the cerebral cortex levels of T4. The effects of subchronic
      treatment with PM and DM on the concentrations of T3 were further investigated in
      the subcellular fractions, namely nuclei, mitochondria, myelin and synaptosomes
      of the cerebral cortex and hippocampus. PM treatment induced a decrease in the
      nuclear and synaptosomal concentrations of T3 of either the cerebral cortex or
      hippocampus, whereas DM reduced the levels of T3 especially in the mitochondria
      of the cortex and hippocampus. CONCLUSIONS: Treatment with pyrethroids
      subchronically to the rats would affect the serum and brain tissue levels of T4
      and T3. These results indicate that the pyrethroids-induced neurotoxicity may
      involve at least in part an impairment of the physiological action of T3 at its
      subcellular targets.

PMID- 14694633
TI  - [Study on the silica-induced cytotoxicity and hprt gene mutagenisis in rat lung
      fibroblasts and alveolar type II epithelial cells].
AB  - OBJECTIVE: To explore the differences of the silica-induced inhibition on
      cellular proliferation and hprt gene mutagenesis between lung fibroblasts and
      alveolar type II cells. METHODS: The proliferation inhibitive cytotoxicity was
      detected by MTT (3-[4,5-Dimethylthiazolzyl]-2,5-Diphenyl Tetrazolium Bromide)
      colorimetric method. Mutation in the hprt gene was screened by culture in the
      presence of the toxic purine analog, 6-thioguanine (6-TG). RESULTS: Under the
      same circumstances of silica exposure, alveolar type II cells was more sensitive
      than lung fibroblasts for proliferation inhibition. The median proliferation
      inhibition concentration (IC50) of silica on epithelial was 140 micrograms/cm2,
      whereas IC50 of silica on fibroblasts was 282 micrograms/cm2. At the same doses
      of silica, the hprt gene mutation frequency in type II cells (84.2 x 10(-6))
      156.6 x 10(-6) was statistically higher than that in fibroblasts (67.6 x 10(-6)
      114.3 x 10(-6), P < 0.05). CONCLUSION: There were significant differences of both
      silica-induced cell proliferation inhibition and hprt gene mutation between rat
      lung fibroblasts and type II epithelial cells. In vitro, cultured rat alveolar
      type II cells were more sensitive in cytotoxicity and hprt gene mutagenesis to
      silica dust than lung fibroblasts were.

PMID- 14694634
TI  - [Quantitative experimental study of pneumoconiotic changes in the lungs by dusts
      containing free silica].
AB  - OBJECTIVE: To explore the integrative quantitative index of the extent of
      pneumoconiotic changes by dusts and to evaluate the extent of pulmonary injury by
      the dusts containing different contents of free silica. METHODS: In accordance
      with the morphometric principle, the areas of each kind of pathologic changes in
      the lung tissue sections of pneumoconiosis model were measured by utilizing a
      computer-aided graphic analyzer, and the volume density of each pathologic change
      and the value of pulmonary injury by dust(VPID) were calculated. Meanwhile the
      extent of pulmonary injury were compared among the rat groups treated with the
      dusts containing different contents of free silica. RESULTS: There were
      significant differences among each groups in the volume density of some
      pathologic changes in the same exposed periods. There were significant
      correlation between VPID and the content of free silica dust or the lung collagen
      content (r = 0.535-0.849, P < 0.005 or P < 0.01). Furthermore, the degree of cor
      relationship of VPID with both of the latter were higher than the sum of
      unweighted volume density of the various pathologic changes in lung. CONCLUSION:
      It is suitable, reasonable and simple to use VPID an index to indicate the extent
      of pulmonary injury by dust and to diagnose pneumoconiosis in pathology, and the
      extent of pulmonary injury by dust may be aggravated with the increasing of the
      content of free silica.

PMID- 14694635
TI  - [The retrospective survey of malignant tumor in weapon workers exposed to 2,4,6
      trinitrotoluene].
AB  - OBJECTIVE: To investigate the occupational health risk level of workers exposed
      to 2,4,6-trinitrotoluene (TNT) in arms industry, so as to provide basis for
      revising the standard of diagnosis for chronic TNT poisoning, and making
      protective measures for workers. METHODS: The retrospective study about the
      morbidity of total malignant tumor was taken on the male workers exposed to TNT
      over one year from eight military factories during 1970 to 1995. RESULTS: The
      morbidity of total malignant tumor in male TNT exposed workers were markedly
      higher than that of controls, and the relative risk (RR) was 2.32. Compared with
      the total malignant tumor mortality of male populations in large and medium
      cities in 1973 to 1975 and 1990 to 1992, the standardized mortality ratio(SMR)
      were 71.8 and 179.6 respectively, the CI of 99% was 71.8-144.2, indicating that
      the morbidity of malignant tumor of male workers exposed to TNT was higher than
      that of normal populations. Liver cancer morbidity was 31.91% of the total
      malignant tumor, and its mortality was 3.97 times of the controls. Compared with
      the liver cancer mortality of male populations in large and medium cities in 1973
      to 1975 and 1990 to 1992, SMR were 150.5 and 381.6 respectively, these data were
      significantly different, and CI of 99% was 59.3-184.0. The average death age of
      the TNT exposed workers (51.7 years old) was younger than that of the same
      factory control(54.1 years old) and male populations(55.6 years old) in large and
      medium cities. The incidence of liver cancer was closely related to the length of
      service, the kinds of job in a factory and the level exposed to TNT, and alcohol
      consumption was synergistic with TNT carcinogenesis. CONCLUSION: The morbidity of
      malignant tumor of male workers exposed to TNT was markedly higher than that of
      normal populations. Liver cancer was the most remarkable malignancy, and its
      incidence was closely related to the length of service and the kinds of job and
      the level exposed to TNT.

PMID- 14694636
TI  - [The relationship between hemoglobin adducts of trinitrotoluene and exposed
      level].
AB  - OBJECTIVE: To explore the biomarkers for monitoring trinitrotoluene (TNT)
      exposure, the relationship between TNT hemoglobin adducts and TNT exposed level.
      METHOD: Hemoglobin adducts (4A-Hb and 2A-Hb) were determined by GC-MS in 25 TNT
      exposed workers. TNT exposed level was evaluated by determining skin contaminated
      and inhaled TNT levels. The correlation between hemoglobin adducts level and TNT
      exposed level was analyzed. RESULTS: There was a correlation between total TNT
      exposure level, especially skin exposure level, and 4A-Hb or 2A-Hb content. No
      significant difference was found between the slopes and intercepts of lin ear
      equation of (4A-Hb) vs TNT exposed level and linear equation of (4A-Hb +2A-Hb) vs
      TNT exposed level (P > 0.05). CONCLUSION: Skin contamination is the major role of
      TNT exposure. TNT exposed level can be evaluated by determining the content of
      both 4A-Hb and 2A-Hb, and 4A-Hb is more suitable for monitoring TNT exposure.

PMID- 14694637
TI  - [Study on the correlation of the biochemical indexes in flouride workers].
AB  - OBJECTIVE: To explore the correlation among some biochemical indexes in the
      fluoride workers. METHODS: The activities of superoxide dismutase(SOD),
      glutathione peroxidase (GSH-Px), catalase (CAT), alkaline phosphatase (AKP) and
      the level of calcitonin (CT), parathyroid hormone (PTH), IgG, IgA, IgM, Cu2+,
      Zn2+, Ca2+, Mg2+ and Se2+, F- in serum and in urine were measured in fifty male
      fluoride workers and fifty controls. RESULTS: The levels of F-, CT, PTH, AKP and
      GSH-Px in serum and F- in urine in exposed group were significantly different
      from that in control group. Correlation analysis indicated that F- in urine and
      CAT(r = 0.3133, P < 0.05), CT and PTH(r = 0.5173, P < 0.01), Se2+ and CAT(r =
      0.4354, P < 0.05) were positively correlated. There were significantly negative
      correlation between F- in serum and GSH-Px (r = -0.5202, P < 0.01) and positive
      correlation among Cu2+, Zn2+, Ca2+ and Mg2+ in serum. CONCLUSION: (1) Excess of
      fluoride may affect secretion of calcium adjusting hormone (CT, PTH); (2) Changes
      of AKP and GSH-Px may be regarded as health monitoring indexes; (3) The
      correlation of biochemical indexes plays an important role in studying the
      mechanism and the early prevention and treatment of industrial fluorosis.

PMID- 14694638
TI  - [Effect of acrylamide on creatine kinase and adenosine triphosphate in brain of
      mice and its significance].
AB  - OBJECTIVE: To explore the changes of brain energy metabolism following acrylamide
      (ACR) poisoning. METHODS: Creatie kinase (CK), adenosine triphosphate (ATP),
      adenosine diphosphate(ADP), adenosine 5'-monophosphate(AMP) and glucose contents
      in brain were observed in O1a mice and 6J mice following ACR intoxication by
      enzyme analytical method. RESULTS: ATP, CK and glucose levels decreased
      transiently in O1a mice, while ATP level in 6J mice was significantly decreased
      (1.76 mumol/g, P < 0.01), as compared to the control (2.53 mumol/g) but ADP and
      AMP were increased, glucose was decreased. The activity of CK in poisoned group
      (1.13 mumol/g, P < 0.01) was lower than that of control (3.16 mumol/g and lasted
      for 5 weeks). CONCLUSION: The influence of ACR on O1a mice was slight and
      reversible but on 6J mice was severe and lasting. There was severe damage to the
      potential energy supply compensation, which might be the biochemical basis of
      neuron damage induced by acrylamide.

PMID- 14694639
TI  - [The study of DNA damage of peripheral lymphocytes in the nurses occupationally
      exposed to anticancer drugs].
AB  - OBJECTIVE: To detect the DNA damage of the nurses occupationally exposed to
      anticancer drugs and to assess the exposure level using Comet assay. METHODS:
      Sixteen nurses occupationally exposed to anticancer drugs were selected as
      exposure group, the average exposure period was 5.6 years, and the average
      exposure dose was to prepare 7.8 portions of anticancer drugs daily. Meanwhile,
      sixteen nurse students were selected as control group. The DNA migration of the
      peripheral lymphocytes of both groups was detected using comet assay. RESULTS:
      The comet length was 46.27 microns in exposure group, which was significantly
      higher than that of control group (26.78 microns, P < 0.01). Also the percentage
      of long tailed nucleus (LTN) of exposure group was 64.83%, which was
      significantly higher than that of control group (4.87%, P < 0.01). CONCLUSIONS:
      There was DNA damage in the nurses occupationally exposed to antineoplastic
      drugs.

PMID- 14694641
TI  - [Consequence calculation of a leak for liquid ammonia storage tank].
AB  - OBJECTIVE: To calculate the consequence of acute ammonia poisoning accident which
      was caused by the leak of liquefied ammonia storage tank, so as to provide
      theoretical basis for working out the counterplan of accidents. METHOD: The
      amount of liquefied ammonia to be reserved, the pressure and temperature inside
      the tank were inputted; based on the physical chemistry principle, the
      evaporating amount was calculated; and using the proper diffusion model, the size
      of ammonia cloud, percentages of death and depth range of the poisonous gas etc
      was calculated. RESULTS: Assuming the leaky tank had liquefied ammonia 50 t, the
      pressure and the temperature were 2.5 MPa and 30 degrees C respectively, the
      evaporating amount and the size of ammonia cloud were calculated. The radiuses,
      of the ammonia released cloud of severe, moderate and mild hazard were 108 m, 216
      m, 370 m respectively; if the exposured time was 30 min, the percentage of death
      would be 50%; if the exposured time was 5 min, the percentage would be 10%; if
      the exposured time was 2 min, the percentage would be 2.5%. When the stable
      degree of circumstance was C, the wind speed was 2.3 m/s and the outside
      concentration of the cloud was 4000 mg/m3, dimension of cloud in X axis was 782 m
      and in Y axis was 88 m. CONCLUSION: The leaky consequence of liquefied ammonia
      was very serious. It is necessary to take preventive measures during production,
      storage, transportation and using of liquefied ammonia.

PMID- 14694640
TI  - [Evaluation of urinary ortho-cresol as biological monitoring indicator of
      occupational exposure to toluene].
AB  - OBJECTIVE: To investigate the feasibility of urinary ortho-cresol levels as a
      biological monitoring indicator for toluene exposure. METHODS: Establish pre
      column derivation HPLC method to detect ortho-cresol levels in urine of human
      body. Ortho-cresol levels in urine of workers non-exposed and exposed to toluene
      was examined using this pre-column derivation HPLC method, and exposure
      assessment was conducted. RESULTS: It was shown that urinary ortho-cresol level
      in exposed workers was (2.61 +/- 1.94) mg/L, higher than those of control group
      [(0.32 +/- 0.23) mg/L, P < 0.001]. Urinary ortho-cresol level in exposed workers
      at the end of a workshift was higher than those before exposure to toluene, and
      also was correlated with the concentration of toluene to which individual
      exposed(r = 0.6295, P < 0.01). CONCLUSION: Urinary ortho-cresol as a biological
      monitoring indicator for toluene exposure is feasible.

PMID- 14694642
TI  - [Study of the volatilization inhibitor for formalin].
AB  - OBJECTIVE: To find an inhibitor to reduce the volatilization of formalin. METHOD:
      The saturated solution of sodium hydrosulphite (SHS) was sprayed on the surface
      of the anatomy specimens, then the concentration of formaldehyde in the air was
      tested. RESULTS: The concentration of formaldehyde in the air of SHS sprayed
      group [(3.10 +/- 1.22) mg/m3] was significantly lower than that of the control
      group [(8.36 +/- 4.11) mg/m3, P < 0.01]. CONCLUSION: SHS may be a volatilization
      inhibitor for formalin, which could reduce the concentration of formaldehyde in
      the air.

PMID- 14694643
TI  - [Electromagnetic noise blocks the gap-junctional intercellular communication
      suppression induced by 50 Hz magnetic field].
AB  - OBJECTIVE: To explore whether the superposition of an electromagnetic noise can
      block gap-junctional intercellular communication(GJIC) suppression induced by 50
      Hz 0.4 mT extremely low frequency magnetic field(ELF MF). METHODS: Fibroblast
      cells of mice(NIH 3T3) were exposed to 0.4 mT ELF MF or(and) electromagnetic
      noise with the same intensity of MF for 24 h, and the GJIC was determined by
      using fluorescence recovery after photobleaching(FRAP) analysis, which was
      performed with a laser-scanning confocal microscope(Leica, Germany). RESULTS: ELF
      MF exposure significantly inhibited GJIC with fluorescence recovery rate of
      27.67% +/- 5.12% as compared with the control group(45.57% +/- 9.72%) (P < 0.01),
      while that of ELF MF plus noise group was (52.61% +/- 8.30%), which was
      significantly different from ELF MF group(P < 0.01), but not from control(P >
      0.05). CONCLUSION: Electromagnetic noise could block the GJIC suppression induced
      by 50 Hz 0.4 mT MF.

PMID- 14694644
TI  - [Effects of electromagnetic noise on the enhancement of stress-activated protein
      kinase(SAPK) phosphorylation induced by 50 Hz magnetic fields].
AB  - OBJECTIVE: To investigate the possible interference effect of electromagnetic
      noise exposure on phosphorylation of stress-activated protein kinase(SAPK)
      induced by 50 Hz magnetic field(MF). METHODS: Chinese hamster lung(CHL) cells
      were exposed to sham exposure(C), 0.4 mT 50 Hz sinusoidal MF, 0.4 mT
      electromagnetic noise and the combined noise MF with 50 Hz MF for 3 min and 15
      min respectively. After exposure, the cells were lysed, and the proteins were
      extracted. The SAPK and phosphorylated SAPK (activated form of SAPK) were
      measured indirectly by Western blot with corresponding antibodies. The percentage
      of phosphorylated SAPK was calculated and analyzed. RESULTS: Exposure of cells to
      50 Hz MF for 3 min and 15 min enhanced the SAPK phosphorylation. The percentage
      of phosphorylated SAPK were 49.3% and 57.0% respectively, and were significantly
      different from those of control(P < 0.05, n = 4). However, single noise MF
      exposure with the same intensity did not enhance the SAPK phosphorylation, the
      percentage of phosphorylated SAPK were 37.7% and 31.8% (P > 0.05). When cells
      were exposed to the combined noise MF with 50 Hz MF for 3 min, the SAPK
      phosphorylation was significantly inhibited (24.4%, P < 0.05); for 15 min, the
      SAPK phosphorylation was also decreased (39.0%), but there was no significant
      difference from control and 50 Hz MF exposure(P > 0.05). CONCLUSION: Noise MF
      with certain intensity could inhibit the biological effect induced by 50 Hz MF.

PMID- 14694645
TI  - [The effect of extremely low frequency magnetic fields on cytochrome oxidase
      subunit 1 mRNA transcription].
AB  - OBJECTIVE: To clone and identify MF-1 gene which responded to extremely low
      frequency magnetic fields(ELF MF) in Daudi cells, and explore the response
      universality of MF-1 gene in several MF-sensitive cell lines, so as to provide
      experimental basis for revealing the mechanism of biological effects induced by
      magnetic field. METHODS: The DNA fragment of MF-1 was cloned and sequenced; the
      mRNA level of MF-1 gene were analysed in MF-sensitive cell lines(HL-60, L1210 and
      CHL) by Northern blot after these cells being treated with 0.1 mT and 0.8 mT MF
      for 20 minutes and 24 hours, respectively. RESULTS: The MF-1 cDNA sequence had
      100% homology with cytochrome oxidase subunit 1 gene(CO1) by searching Gene Bank
      database; the transcription of CO1 in HL-60, L1210 and CHL cell lines which
      exposed to 0.1 mT and 0.8 mT MF for 20 minutes were significantly lower(0.38 +/-
      0.12 and 0.37 +/- 0.04) than that of control(0.58 +/- 0.12) and so did for 24
      hours exposure(0.46 +/- 0.09 and 0.45 +/- 0.09 vs 0.65 +/- 0.06) (P < 0.05).
      CONCLUSION: CO1 is a MF-responsive gene. Cytochrome oxidase activity may be
      affected through low level of CO1 transcription by magnetic fields, thus induce
      bioeffects in organisms.

PMID- 14694647
TI  - [Effects of power-frequency magnetic fields exposure on phosphorylation and
      enzymatic activity of stress-activated protein kinase and its upstream kinase].
AB  - OBJECTIVE: To study the effects of 50 Hz power-frequency magnetic fields on
      signal transduction pathway of stress-activated protein kinase(SAPK), and explore
      the cellular signal transduction mechanism of the biological effects induced by
      power-frequency magnetic fields. METHODS: Chinese hamster lung(CHL) cell line was
      exposed to power-frequency magnetic fields with two intensities for different
      exposure durations. The cytoplasmic protein was extracted and the phosphorylated
      portion of SAPK and SEK1/MKK4 was measured with Western blotting analysis. The
      SAPK enzymatic activity was measured by the solid-phase kinase assay in cells
      exposed to power-frequency magnetic fields for 15 min. RESULTS: Both 0.4 mT and
      0.8 mT power-frequency magnetic fields could enhance the phosphorylation of SAPK
      in a time-relative course manner, and reached the maximum extent at 15 min, with
      an increase of 20% and 17% respectively. The solid-phase kinase assay showed that
      the enzymatic activities of SAPK were also increased, which were 2.9 +/- 0.4 and
      2.1 +/- 0.9 times of control respectively. However, the duration of SAPK
      phosphorylation induced by 0.8 mT was longer than that of 0.4 mT, while the
      duration and extent of SAPK dephosphorylation was remarkably shorter than that of
      0.4 mT. The power-frequency magnetic fields under equal conditions could not
      phosphorylate(activate) the SEK1/MKK4. CONCLUSION: Power-frequency magnetic
      fields could activate the SAPK, but not SEK1/MKK4. It is suggested that power
      frequency magnetic fields may activate SAPK signal transduction pathway through a
      kinase other than SEK1/MKK4. The activation mechanism of SAPK of power-frequency
      magnetic fields needs to be identified in more detail.

PMID- 14694646
TI  - [Exposure to power-frequency magnetic fields can induce activation of P38 mitogen
      activated protein kinase].
AB  - OBJECTIVE: To study the effects of 50 Hz power-frequency magnetic fields on
      signal transduction pathway of P38 mitogen-activated protein kinase (P38 MAPK),
      and explore the cellular signal transduction mechanism of the biological effects
      induced by power-frequency magnetic fields. METHODS: Chinese hamster lung (CHL)
      cell line was exposed to power-frequency magnetic fields with two intensities(0.1
      and 0.4 mT) for different exposure durations. The cytoplasmic protein was
      extracted. The phosphorylated(activated) and non-phosphorylated P38 MAPK and
      MKK3/MKK6 were measured by Western blotting analysis with their specific
      corresponding antibodies. RESULTS: Power-frequency magnetic fields at 0.4 mT for
      10 min could transitorily induce the activation of P38 MAPK and after 15 min the
      phosphorylation of P38 MAPK restored to control level, while 0.1 mT power
      frequency magnetic fields could not induce the activation of P38 MAPK within 24
      h. However, both 0.1 mT and 0.4 mT power-frequency magnetic fields could not
      phosphorylate(activate) the MKK3/MKK6, which is a general upstream kinase of P38
      MAPK. CONCLUSION: Power-frequency magnetic fields could transitorily activate the
      P38 MAPK, but not MKK3/MKK6. The activation mechanism of P38 MAPK needs to be
      further identified.

PMID- 14694648
TI  - [Abnormal shift of connexin 43 gap-junction protein induced by 50 Hz
      electromagnetic fields in Chinese hamster lung cells].
AB  - OBJECTIVE: To study the effects of extremely low frequency magnetic fields(ELF
      MF) on the amount and localization of connexin 43(Cx43) gap-junction protein in
      the Chinese hamster lung(CHL) cells, and to explore the mechanism of ELF MF
      suppression on gap-junctional intercellular communication(GJIC). METHODS: The
      cells were irradiated for 24 h with 50 Hz sinusoidal magnetic field at 0.8 mT
      without or with 12-O-tetrade-canoylphorbol-3-acetate(TPA), 5 ng/ml for 1 h. The
      localization of Cx43 proteins were performed by indirect immunofluorescence
      histochemical analysis and detected by confocal microscopy. The second experiment
      was conducted to examine the quantity of Cx43 proteins level in nuclei or
      cytoplasm and detected by Western blotting analysis. RESULTS: The cells exposed
      to TPA for 1 h displayed less bright labelled spots in the regions of
      intercellular junction than the normal cells. Most of Cx43 labelled spots
      occurred in the cytoplasm and aggregated near the nuclei. At the same time, the
      amount of Cx43 protein in cytoplasm were increased[(2.03 +/- 0.89) in ELF group,
      (2.43 +/- 0.82) in TPA group] as compared to normal control(1.04 +/- 0.17) (P <
      0.01). CONCLUSION: Inhibition on GJIC function by ELF MF alone or combined with
      TPA may be related with the shift of Cx43 from the regions of intercellular
      junction to the cytoplasm.

PMID- 14694649
TI  - [Effects of extremely low frequency electromagnetic field and its combination
      with lead on the antioxidant system in mouse].
AB  - OBJECTIVE: To study the effects of extremely low frequency electromagnetic
      field(ELF EMF) and its combination with lead on the antioxidant system in mouse
      brain and liver tissues. METHOD: Mice were exposed to a 50 Hz sinusoidal 0.2 mT
      or 6.0 mT EMF for 2 weeks. At the same time, some groups were exposed to lead(50
      mg/kg). After the exposure, the antioxidant system and cell membrane fluidity in
      brain and liver were measured. RESULTS: Malondiadehyde(MDA) content in brain and
      liver increased from the control levels of (1.33 +/- 0.12) and (3.95 +/- 0.21)
      nmol/mg pro to (1.35 +/- 0.09) and (6.15 +/- 0.28) nmol/mg pro respectively
      following 0.2 mT exposure, and to (3.98 +/- 0.10) and (6.50 +/- 0.79) nmol/mg pro
      respectively following 6.0 mT exposure. Total antioxidant capability(T-AOC) in
      brain and liver decreased from the control levels of (4.39 +/- 0.48) and (2.45 +/
      0.21) U/mg pro to (3.99 +/- 0.39) and (1.92 +/- 0.32) U/mg pro respectively
      following 0.2 mT, and to (3.12 +/- 0.37) and (1.57 +/- 0.14) U/mg pro
      respectively following 6.0 mT. GSH content decreased only in liver tissue from
      the control level of (194.60 +/- 20.93) mg/g pro to (189.24 +/- 5.61) mg/g
      pro(0.2 mT) and (153.04 +/- 1.18) mg/g pro(6.0 mT). Cellular membrane fluidity
      decreased from the control levels of (1.396 +/- 0.040) and (2.899 +/- 0.552) to
      (1.224 +/- 0.190) and (1.894 +/- 0.0761) (0.2 mT), (1.159 +/- 0.179) and (1.516
      +/- 0.204)(6.0 mT) respectively. Compared with single EMF exposure(6.0 mT), EMF
      combined with lead exposure induced remarkable increase in MDA, GSH content and T
      AOC and decrease in cell membrane fluidity both in the brain and liver, and
      increase in SOD activity only in liver. CONCLUSION: ELF EMF might alter the
      metabolism of free radicals, decrease anti-oxidant capability and enhance lipid
      peroxidation. The combination of EMF with lead showed synergic effects on lipid
      peroxidation.

PMID- 14694650
TI  - [The effects of electromagnetic pulse on fluidity and lipid peroxidation of
      mitochondrial membrane].
AB  - OBJECTIVE: To study the effects of intense electromagnetic pulse(EMP) on the
      biological effects of mitochondrial membrane. METHOD: Rat liver mitochondrial
      suspension was exposed to EMP at 60 kV/m level. The changes of membrane lipid
      fluidity and membrane protein mobility were detected by ESR and spin label
      technique. Malondialdehyde(MDA) was detected by spectrophotometer. RESULTS: The
      mobility of membrane protein decreased significantly(P < 0.05). Correlation time
      (tau c) of control group was (0.501 +/- 0.077) x 10(-9)s, and tau c of EMP group
      was (0.594 +/- 0.049) x 10(-9)s, indicating that the mobility of protein was
      restricted. The fluidity of mitochondrial membrane increased significantly(P <
      0.05) at the same time. Order parameter(S) of mitochondrial membrane lipid in
      control group was 0.63 +/- 0.01, while S of EMP group was 0.61 +/- 0.01(P <
      0.05). MDA decreased significantly. CONCLUSION: The mobility and lipid
      peroxidation of mitochondrial membrane may be disturbed after EMP exposure.

PMID- 14694651
TI  - [Change of catecholamine in serum and hippocampus of rats after electromagnetic
      irradiation and the selection of protective site].
AB  - OBJECTIVE: To study the role of catecholamine(CA) in the mechanism of bio-effect
      of electromagnetic irradiation. METHODS: The contents of norepinephrine (NE),
      epinephrine (E) and dopamine (DA) in serum and hippocampus of rats at 0, 8, 24,
      48 hours after electromagnetic irradiation were measured by using high
      performance liquid chromatography with electrochemical detector(HPLC-ECD), and
      the influence of two kinds of shelter on CA was studied. RESULTS: The levels of
      CA in serum and hippocampus increased obviously in an instant, decreased at 8 h
      and increased significantly again at 24 h after irradiation without shielding
      irradiation. But at 48 h, the levels of NA, DA in hippocampus were still higher
      and the serum's NA, DA were not different from the control. After irradiation
      with whole body shielding, the levels of CA had no changes. The contents of CA
      increased significantly only at 24 h after irradiation by 65 W/cm2
      electromagnetic wave with trunk shielding. After irradiation by 129 W/cm2 with
      trunk shielding, the change of CA were similar to that of no shielding.
      CONCLUSION: CA may take part in the injury to central nervous system and
      cardiovascular system after electromagnetic irradiation. And the injury to
      central nervous system may sustain longer than that of cardiovascular system. The
      protective effect of whole body shielding is the best, while trunk shielding may
      have some protective effect following lower and middle power electromagnetic
      wave. The most important protective measure is to shield the head.

PMID- 14694652
TI  - [Effect of low-intensity microwave of on mitomycin C-induced genotoxicity in
      vitro].
AB  - OBJECTIVE: To study that low-intensity microwave whether or not enhances the
      genotoxic effects of mitomycin C(MMC) on human lymphocytes. METHODS: Single
      strand DNA breaks and chromosomal aberrations were measured by comet assay and
      cytokinesis-blocked micronucleus(CBMN) test in vitro when human lymphocytes were
      exposed to 2,450-MHz microwave (5.0 mW/cm2) alone and in combination with
      mitomycin C. RESULTS: In the comet assay, the average comet lengths of microwave
      group[(29.1 +/- 8.1) micron in male and (25.9 +/- 7.5) micron in female] were not
      significantly different from those of control groups [(26.3 +/- 6.6) and (24.1 +/
      4.3) micron respectively] (P > 0.05). The average comet lengths of MMC
      group(0.0125, 0.0250, 0.0500, 0.1000 microgram/ml) were significantly longer than
      those of control groups (P < 0.01) and were increased with the dose of MMC. The
      average comet lengths of microwave combined with MMC (MW + MMC) also were
      increased with the doses of MMC and were significantly longer than those of
      control groups (P < 0.01). When MMC was > or = 0.0250 microgram/ml, microwave and
      MMC synergistically increased the single strand DNA breaks. In the micronucleus
      test, the average micronucleus rates of microwave groups were not higher than
      those of control groups (P > 0.05). The average micronucleus rates of MMC groups
      and MW + MMC groups were significantly higher than those of control groups (P <
      0.01) when MMC was > or = 0.0500 microgram/ml. The average micronucleus rates of
      MW + MMC groups seemed higher than those of corresponding MMC groups, however the
      difference was not significant (P > 0.05). CONCLUSION: Low-intensity(2,450-MHz)
      microwave did not induce DNA and chromosome damages on human lymphocytes, but
      enhanced the effects of DNA breaks induced by MMC.

PMID- 14694653
TI  - [The polymorphism of delta-aminolevulinic acid dehydratase and genetic
      susceptibility to lead toxicity in Uighur and Yi population in China].
AB  - OBJECTIVE: To investigate the polymorphism of delta-aminolevulinic acid
      dehydratase(ALAD) and the genetic susceptibility to lead toxicity in Uighur and
      Yi population in China. METHODS: The ALAD genotypes were determined by PCR and
      MspI restriction fragment length polymorphism techniques in 214 Uighur
      individuals from Xinjiang autonomous region and 144 Yi individuals from Yunnan
      province. The correlation between the polymorphism of ALAD and blood lead levels,
      and the factors affecting the latter were explored. RESULTS: The frequencies of
      the allele ALAD1 and ALAD2 in Uighur are 0.91 and 0.09; and in Yi are 0.98 and
      0.02 respectively. In Uighur the average blood lead level was (76 +/- 4)
      microgram/L, and 25.7% individuals with blood lead level > or = 100 micrograms/L.
      In Yi the average blood lead level was (50 +/- 16) microgram/L, and 6.3%
      individuals with blood lead level > or = 100 micrograms/L. However, no statistic
      correlation between the distribution of ALAD alleles and the blood lead level was
      found in both populations. CONCLUSION: The genetic susceptibility of ALAD
      polymorphism to lead toxicity may exhibit in a lead dose-dependent manner.

PMID- 14694654
TI  - [Difference in lymphocyte heat shock protein 71 (HSP71) expression in soldiers of
      armed police forces from different climatic zones].
AB  - OBJECTIVE: To analyze the difference between basal and heat-inducible levels of
      lymphocyte heat shock protein 71 (HSP71) expression in soldiers from Beijing,
      Zhengzhou and Guangzhou. METHODS: Flow cytometry and Comet assay were used to
      detect the level of HSP71 and DNA damage respectively. RESULTS: Comet assay
      showed that there was no significant DNA damage before and after heat stress at
      41 degrees C for 1 h, and also no difference found among the 3 climatic zones(P >
      0.05). HSP71 of all soldiers in the 3 zones elevated after stress (P < 0.05). The
      basal and heat-inducible levels of HSP71 in Beijing soldiers(845.87 +/- 135.60
      and 1254. 47 +/- 239.05 mean fluorescence intensity respectively) were higher
      than those in Guangzhou soldiers(702.73 +/- 184.70 and 861.72 +/- 225.12 mean
      fluorescence intensity respectively) (P < 0.05). CONCLUSION: The differences of
      lymphocyte HSP71 expression before and after heat stress among the soldiers from
      Beijing, Zhengzhou and Guangzhou suggest that basal and heat-inducible levels of
      lymphocyte HSP71 expression may be considered as a valuable index to evaluate
      heat tolerance of soldiers in different climatic zones.

PMID- 14694655
TI  - [The expression of heat shock protein 70 (HSP70) in the cells of rat liver and
      cardiac muscle in different heat exposure stages].
AB  - OBJECTIVE: To show the changes of heat shock protein 70(HSP70) expression at
      cellular level in different heat exposure stages and the significance of HSP70
      expression in heat exposure organism. METHOD: The heat exposure model was
      established in rats with artificial hot climatic chamber[34 +/- 1) degree C, RH
      60%]. SD rats were randomly divided into control groups(C) and heat exposure
      groups(A), and into subgroups including 2, 7, 14, 28 d stages from each one of
      the groups. The immuno-histochemistry was used to detect HSP70 expression in rat
      liver and cardiac muscle, and photography analytic software was used to analyze
      HSP70 expression in liver and cardiac cells. RESULTS: The expression intensity of
      HSP70 in heat exposure groups(gray values of liver were 137.0 +/- 5.1, 137.0 +/-
      5.2, 137.8 +/- 7.1, 139.2 +/- 5.2 respectively; of cardiac muscle 156.1 +/- 4.4,
      155.1 +/- 6.2, 155.4 +/- 4.5, 156.2 +/- 5.1 respectively) was stronger than that
      in control groups(P < 0.01 or P < 0.05) during all stages of the heat exposure;
      There was no significant difference in expression intensity of HSP70 among
      various stages of heat exposure; after 2 d of heat exposure, HSP70 expression in
      cell nuclei of the liver and cardiac muscle cells was stronger than that in
      cytoplasm in heat exposure group; HSP70 expression in Kupffer's cells of liver
      was also stronger than that of control(P < 0.05), but not on 7, 14 and 28 d; the
      activities of alanine aminotransferase(ALT), aspartate aminotransferase(AST),
      creatine kinase(CK) and hydroxybutyrate dehydrogenase(HBD) showed an increase on
      2 d and 28 d of heat exposure. CONCLUSION: The vital organs would be damaged on 2
      d of heat exposure. High expression of HSP70 at this stage may be a marker of
      cell damage; Increased HSP70 expression on 7-14 d of heat exposure may play an
      important role in adaptation to heat, while long term(28 d) heat exposure, the
      protection of HSP70 from tissue damage may not be enough.

PMID- 14694656
TI  - [An analysis of the main causes of death in different industrial systems in
      Guangzhou].
AB  - OBJECTIVE: To study the main causes of death in workers from different industries
      in Guangzhou. METHODS: The industrial systems in Guangzhou were classified into
      six categories according to the Chinese Public Health Inspection Statistical
      Report. Baseline data on 79,547 workers, age > or = 35, were retrieved from
      individual health records under the Guangzhou Occupational Health Surveillance
      Record System established in 1989-1992. In this prospective cohort study, the
      workers' vital status and causes of death were followed up until 31 December
      1998. Using SPSS 10.0, crude death rates were calculated and relative risks(RR)
      (95% CI) were estimated using Cox proportional-hazard models. RESULTS: (1) Among
      79,547 workers were 49,355 men and 30,192 women, with mean age of (43.8 +/- 6.5)
      years, and 64% were aged 35-44. The mean age difference of workers in different
      industries was +/- 1 year. At baseline, 41% had been exposed to occupational
      hazards. Exposure was most prevalent in petroleum chemical industry(53.9%),
      followed by metallurgical industry, and the lowest exposure was in mechanical
      industry (30.2%). (2) The mean follow-up period was (8.0 +/- 1.3) years with
      633,510 person-years. 1,577 workers had died with a total death rate of 248.9 per
      100,000 person-years. The death rate in rubber industry was the highest, followed
      by metallurgical and petroleum chemical industries. Malignant neoplasms, vascular
      and respiratory diseases were most common, constituting 80.3% of all causes of
      death. (3) For all causes of death and the three main categories, the top three
      crude death rates were observed in rubber and petroleum chemical industries, and
      in the metallurgical industry except for vascular causes. The rubber industry had
      the highest crude death rate for all and vascular causes, and the metallurgical
      industry for malignant neoplasms and respiratory causes. (4) With the light
      industry as a reference (RR = 1.0), the metallurgical industry had the highest
      adjusted relative risks (RR) (95% CI) of 1.62(1.20-2.18) and 7.42(3.38-16.31) for
      malignant neoplasms and respiratory causes, respectively. The rubber industry had
      the highest RR of 1.69(1.40-2.04) for all causes. A significant RR of 2.03(1.43
      2.88) for vascular causes was observed only in the rubber industry. CONCLUSIONS:
      The main causes of death varied from industry. Malignant neoplasms and
      respiratory diseases were the leading causes in metallurgical and petroleum
      chemical industries. In rubber industry, vascular and respiratory causes were
      most common. Preventive measures for disease control should be tailor-made for
      each industry.

PMID- 14694657
TI  - [The acute effects of dimethoate on the muscarinic-receptors of rat brains and
      the relationship between muscarinic-receptors and cholinesterase].
AB  - OBJECTIVE: To study the acute effects of dimethoate on the muscarinic
      receptors(M1, M2) in the brain of rats. METHODS: 24 Sprague-Dawley rats were
      divided into 4 groups randomly. They were administered subcutaneously with 0, 25,
      50, 100 mg/kg dimethoate, respectively. Brains were removed after 48 hours of
      administration. Radioligand binding assay was used to determine the density and
      affinity of M1 and M2 receptors. RESULTS: Rats in the treated group showed low
      density of M1 and M2 receptors compared with the control rats. The brain M1
      receptor density of the rats in the highest dosage group was significantly lower
      than that in the control group while brain M2 receptors density had a decrease
      trend with increasing dosage, but the difference showed no significance. However,
      there were no differences of the affinity of both M1 and M2 among different
      treated groups. Correlation analysis showed there is positive relationship
      between cholinesterase activity and density of M1 receptors(r = 0.583, P < 0.01).
      CONCLUSION: M1 and M2 receptors density decreased with the increasing dosage of
      dimethoate. It is suggested that the alleviating of cholinergic symptoms may be
      due to the decrease of M1 and M2 receptors in rat brain.

PMID- 14694658
TI  - [Study on the morphological damage and cell apoptosis of nerve tissue in mice
      exposed to benzo[a]pyrene].
AB  - OBJECTIVE: To study the toxicological effects of benzo[a]pyrene(BaP) on mammalian
      animal's nerve tissue. METHODS: 50 Kunming mice were divided into 5 groups at
      random, the exposed groups(3 dose level groups), the vehicle control group and
      standard control group. Every group got 10 mice. The exposed groups were treated
      by intraperitoneal injection with BaP dissolved in vegetable oil at 7.8, 3.2 and
      1.3 mg/kg respectively, 4 times/week, for 10 weeks, the vehicle control group
      were given vegetable oil and the standard control group were not given any
      treatment. All the mice were anesthetized with 0.02 mol/L pentobarbital and
      infused with 1.33 mol/L paraformaldehyde dissolved in PBS through heart after 10
      weeks. Then the brain, spinal cord and sciatic nerve were removed. Slices of
      these tissues were made and morphological changes were observed by optical
      microscope and electron-microscope. Cell appoptosis was examined by TUNEL(TdT
      mediated x-dUTP nick end labeling) method. RESULTS: Morphological observations
      showed tissue injury in BaP exposed groups. There were focal necrosis areas found
      in the high-dose group. The cell apoptosis rates in 3.2 and 1.3 mg/kg groups were
      90.02%-94.22% and 62.45%-77.54% respectively, significantly higher than those of
      vehicle control group and standard control group(4.60%-5.57%). CONCLUSION: BaP is
      neurotoxic. It could damage the nerve tissue as well as induce DNA breaks and
      cell apoptosis.

PMID- 14694659
TI  - [Effect of fluoroacetamide on cardiomyocytes of rat and the antidotal effect of
      acetamide].
AB  - OBJECTIVE: To observe the effect of fluoroacetamide on cardiomyocytes of rat and
      the antidotal effect of acetamide. METHODS: 4 groups of SD rats were treated with
      various dosages of fluoroacetamid(p.o.) and 2 groups of them were treated with
      acetamide(i.p.). The changes of cardiomyocytes and serum AST, LDH, CK, CK-MB and
      HBDH were measured at different intervals after poisoning. RESULTS: In the group
      treated with fluoroacetamid 8 mg/kg. bw, serum AST[(589.58 +/- 821.72) U/L],
      CK[(916.78 +/- 343.55) U/L], HBDH[(504.47 +/- 148.88) U/L] raised obviously
      compared with control[(187.70 +/- 46.87), (755.65 +/- 498.90), (347.25 +/-
      228.40) U/L respectively] (P < 0.01), and the pathological findings such as
      degeneration, liquefactive necrosis and filtration of inflammatory cells in
      cardiac muscles were observed 24 hours later, while all the male dead within 3
      days. In the group treated with fluoroacetamid 4 mg/kg. bw, serum LDH and HBDH
      rose significantly compared with control(P < 0.01) 5 day later. On the day of 10,
      myocardial enzymes restored in all experiment groups with some interstitial
      fibroblastic proliferation. The pathological changes were reduced in the group
      treated with acetamide synchronously (100 mg/kg. bw). CONCLUSION: Acute
      intoxication of fluoroacetamide could damage cardiomyocytes while acetamide could
      reduce the injury of them, but the injury was reversible. The levels of serum
      myocardial enzymes could be a usable index for early diagnosis.

PMID- 14694660
TI  - [Relationship between blood NO and PaO2 or PaCO2 levels of patients with acute
      carbon monoxide poisoning].
AB  - OBJECTIVE: To investigate the relationship between blood nitrogen monoxide(NO)
      and PaO2 or PaCO2 levels in patients with severe and moderate acute carbon
      monoxide poisoning. METHOD: The blood levels of NO in patients with severe and
      moderate acute carbon monoxide poisoning was assayed with nitrate reductase
      method, and its correlation with the blood levels of PaO2 and PaCO2 was analyzed.
      RESULTS: The blood level of NO in patients with severe and moderate acute carbon
      monoxide poisoning were (36.6 +/- 9.9) and (35.7 +/- 10.7) mumol/L respectively,
      significantly lower than that of control group[(64.9 +/- 14.3) mumol/L, P <
      0.01], but there was no significant difference between moderate and severe
      patients(P > 0.05). The analysis of linear correlation showed that there was
      significant positive correlation between NO and PaO2 but not PaCO2. CONCLUSION:
      Anoxia of patients with acute carbon monoxide poisoning may be an important cause
      to reduce NO level in blood. This study provides the basis for low NO
      concentration inhalation in treatments of acute carbon monoxide poisoning.

PMID- 14694661
TI  - Fluency in the consulting room.

PMID- 14694662
TI  - Screening for domestic violence in general practice: a way forward?

PMID- 14694663
TI  - Identification of stroke in the community: a comparison of three methods.
AB  - BACKGROUND: Evidence concerning secondary prevention of cerebrovascular disease
      is not optimally used in clinical practice. A necessary first step is to identify
      those eligible for treatment. In primary care, this equates to setting up a
      register of prevalent stroke. AIM: To compare three different methods for
      identifying prevalent cases of cerebrovascular disease in the community: general
      practice-based computer systems; population surveys; and hospital-based routine
      information systems. DESIGN OF STUDY: Comparison of results of each method
      applied to a defined population and then assessed against reference criteria for
      cerebrovascular disease. SETTING: A total of 5801 people aged 65 years or over,
      resident in seven practices situated within the South Birmingham Primary Care
      Trust area. METHOD: The sensitivity, specificity, and predictive value of each
      method of identification were calculated against reference criteria applied by
      two investigators independently of each other. RESULTS: The prevalence of
      reference criteria-validated cerebrovascular disease in patients aged 65 years or
      over was 8.2%. Overall, general practice-based computer systems had a sensitivity
      of 81.0%, a specificity of 97.2% and a positive predictive value (PPV) of 71.8%,
      but there was a wide range of sensitivity (33% to 90%) and PPV (42% to 92%)
      between practices. Patient survey and hospital information systems were less
      sensitive (75.7% and 28.4%, respectively) but had higher PPVs (77.5% and 89.2%,
      respectively). Thirty-nine per cent of patients with a history of cerebrovascular
      disease had not been admitted to hospital. CONCLUSION: General practice-based
      computer systems can produce reasonably accurate prevalent stroke registers. In
      areas where these are poorly developed, patient survey is an alternative.

PMID- 14694664
TI  - Presentation and management of acne in primary care: a retrospective cohort
      study.
AB  - BACKGROUND: Acne is the most common skin disorder in young people, affecting up
      to 80% of teenagers. AIMS: To ascertain the incidence, prevalence, demographic
      distribution and severity of acne in primary care and to document the management
      of these patients for a two-year period after presentation. DESIGN OF STUDY:
      Retrospective cohort study using data from the medical records of 798 patients
      who had been treated for acne during a one-year identification period. SETTING:
      Fourteen general practices in a mixed urban area in north-east England. METHOD:
      Patients aged 13 to 25 years who had acne were identified from computerised
      practice medical records using diagnostic codes and medication records. The
      medical records of these patients were then hand-searched for data for two years
      after presentation. RESULTS: Data were collected for 798 patients from 14
      practices. The prevalence of acne in 13- to 25-year-olds was 3.1%, and the
      incidence was 1.6%. The ratio of male to female patients with acne was 1:1.02.
      Median age at presentation was 15 years for male subjects and 16 years for female
      subjects. Recording of site and severity was rare (18.3%). In total, 55% of
      patients had two or more different prescriptions for acne, 21% of patients had
      six or more consultations during the two-year follow-up period, and 8.5% were
      referred to a dermatologist. CONCLUSION: Given previous estimates of community
      prevalence, it is clear that the majority of young people with acne do not
      present to primary care. These findings have implications for the provision of
      effective and appropriate health care for young people with acne.

PMID- 14694665
TI  - Bilingual young people's experiences of interpreting in primary care: a
      qualitative study.
AB  - BACKGROUND: Young people are often used as interpreters for family members in the
      primary healthcare setting. AIM: To explore bilingual young people's accounts of
      interpreting for family or friends in primary care settings. DESIGN OF STUDY:
      Qualitative study using in-depth interviews. SETTING: Community and youth groups
      in London. METHODS: Young people aged nine to 18 years old (n = 77) were
      purposively sampled to include those from established and recently arrived groups
      and were from Vietnamese, Kurdish, Bangladeshi or Eastern European backgrounds.
      Participants were interviewed one-to-one or with a friend, and interview
      transcripts were analysed to identify key themes. RESULTS: Young people were used
      for interpreting because of deficiencies in services, and also by choice. They
      identified advantages and disadvantages in their experiences. The majority of
      healthcare encounters were regarded as unproblematic. Three factors contributed
      to less successful encounters: healthcare professionals' or patients'
      communication skills; young people's own language skills, and the nature of the
      healthcare problem. CONCLUSION: This study identifies ways in which primary care
      professionals could facilitate better communication in encounters where young
      people are used as interpreters.

PMID- 14694666
TI  - Auditory rehabilitation of older people from the general population--the Leiden
      85-plus study.
AB  - BACKGROUND: Very few older people with severe hearing loss use hearing aids to
      reduce the negative consequences of reduced hearing in daily functioning. AIM:
      Assessment of a screening test and a standardised auditory rehabilitation
      programme for older people from the general population with untreated severe
      hearing loss. DESIGN OF STUDY: Intervention study and qualitative exploration.
      SETTING: Leiden 85-Plus Study, a prospective population-based study of 85-year
      old inhabitants of Leiden, the Netherlands. METHOD: Hearing loss was measured by
      pure-tone audiometry in 454 subjects aged 85 years. Subjects with hearing loss
      above 35 dB at 1, 2, and 4 kHz who did not use hearing aids were invited to
      participate in a standardised programme for auditory rehabilitation. In-depth
      interviews were held with participants to explore arguments for participating in
      this programme. RESULTS: Of the 367 participants with severe hearing loss
      (prevalence = 81%), 66% (241/367) did not use a hearing aid. Three out of four of
      these participants (n = 185) declined participation in the auditory
      rehabilitation programme. The most common reason given for not participating was
      the subjects' feeling that their current hearing loss did not warrant the use of
      a hearing aid. Subjects who participated in the programme were found to suffer
      from more severe hearing loss and experienced more hearing disability. Those who
      did not participate in the programme felt they could cope with their disabilities
      and considered a hearing aid unnecessary. CONCLUSION: Untreated hearing loss is
      prevalent among older people from the general population. The majority of older
      people decline auditory rehabilitation. For these people the use of a hearing aid
      is not perceived as necessary in order to function on a daily basis. Older people
      who have expected benefits from a hearing aid have already obtained them,
      marginalising the benefits of a rehabilitation (and screening) programme.

PMID- 14694667
TI  - Improving communication between physicians and patients who speak a foreign
      language.
AB  - BACKGROUND: Communication between physicians and patients is particularly
      challenging when patients do not speak the local language (in Switzerland, they
      are known as allophones). AIM: To assess the effectiveness of an intervention to
      improve communication skills of physicians who deal with allophone patients.
      DESIGN OF STUDY: 'Before-and-after' intervention study, in which both patients
      (allophone and francophone) and physicians completed visit-specific
      questionnaires assessing the quality of communication. SETTING: Two consecutive
      samples of patients attending the medical outpatient clinic of a teaching
      hospital in French-speaking Switzerland. METHOD: The intervention consisted of
      training physicians in communicating with allophone patients and working with
      interpreters. French-speaking patients served as the control group. The outcomes
      measured were: patient satisfaction with care received and with communication
      during consultation; and provider (primary care physician) satisfaction with care
      provided and communication during consultation. RESULTS: At baseline, mean scores
      of patients' assessments of communication were lower for allophone than for
      francophone patients. At follow-up, five out of six of the scores of allophone
      patients showed small increases (P < 0.05) when compared with French-speaking
      patients: explanations given by physician; respectfulness of physician;
      communication; overall process of the consultation; and information about future
      care. In contrast, physicians' assessments did not change significantly. Finally,
      after the intervention, the proportion of consultations with allophone patients
      in which professional interpreters were present increased significantly from 46%
      to 67%. CONCLUSIONS: The quality of communication as perceived by allophone
      patients can be improved with specific training aimed at primary care physicians.

PMID- 14694668
TI  - Missed opportunities in vaccination of patients with subsequent pneumococcal
      bacteraemia.
AB  - A 10-year survey was undertaken to determine whether patients who developed
      pneumococcal bacteraemia had previously been given pneumococcal vaccine, and
      whether they had previously had the opportunity of being vaccinated. Fifty-two
      per cent of the patients were candidates for vaccine. Of these, only 14% had been
      vaccinated. In the preceding five years, 97% of non-vaccinated patients had the
      opportunity of being assessed for, and administered, vaccine. Guidelines for the
      use of pneumococcal vaccine are not being followed, despite opportunities to do
      so.

PMID- 14694669
TI  - A pilot study to investigate the use of installment dispensing as a method of
      reducing drug wastage owing to adverse drug reactions.
AB  - A new method of dispensing prescribed medicines that are to be taken for longer
      than two weeks was investigated. It was found to reduce drug wastage and produce
      savings in the drugs bill. The scheme was generally well liked by patients,
      doctors, and pharmacists.

PMID- 14694670
TI  - Developing intermediate care provided by general practitioners with a special
      interest: the economic perspective.
AB  - The concept of intermediate care is part of the National Health Service (NHS)
      modernization agenda to make services more flexible and accessible. One objective
      is for the general practitioner with a special interest (GPwSI) to provide a
      variety of extended services in a primary care setting that have been
      traditionally provided in secondary care. This development is underpinned by the
      hope that primary care organisations (PCOs) will provide more effective and
      efficient care in local settings, but, as with other skill-mix changes, the
      process has developed ahead of an evidence base of effectiveness or cost
      effectiveness. This paper considers intermediate care from an economic
      perspective and provides healthcare commissioners with a background that can
      facilitate resource allocation decisions. It cautions that, unless the economic
      issues are carefully considered, there is a danger that services may be
      introduced that are thought to be efficient, when in fact they may not be so.

PMID- 14694671
TI  - Managing violence in primary care: an evidence-based approach.
AB  - An understanding of the risk factors for violence can help primary care staff to
      evaluate and manage risk in the primary care setting. They will be able to
      acknowledge that risk factors are not static but can vary according to time,
      place, situation, and support networks. General practitioners (GPs) should not
      ignore their clinical acumen, but should use their knowledge of the patient to
      form part of a risk assessment. Managing violence in primary care should focus on
      the individual; for example, in the training of primary care staff. It should
      also involve an examination of the wider structure of primary care; for example,
      the safe design of buildings, avoiding long waiting times, and having 'no
      intoxication' policies for practices. There is a pressing need for primary care
      based research in this area. We acknowledge that in our understanding of this
      topic there are two extremes that should be avoided. The first is that our
      perceived risk of violence often exceeds the real, absolute risk. Where our
      perceptions are overstated, patients run the risk of being excluded from primary
      care or of being inappropriately detained on psychiatric wards under the Mental
      Health Act. At the other extreme, where risk is understated, staff can play the
      'hero' or the 'martyr' in an attempt to defuse a situation without support from
      other colleagues. Like many other situations in primary care, working in
      isolation carries real and important risks. Threats of violence are best managed
      in primary care by having a collaborative practice approach underpinned by a
      support ethos from primary care organisations.

PMID- 14694672
TI  - New contract, new dilemmas.

PMID- 14694673
TI  - Do patients want copies of referral letters?

PMID- 14694674
TI  - The consequences of parallel importing.

PMID- 14694675
TI  - Infection in Hong Kong.

PMID- 14694676
TI  - Diagnosis of pneumonia.

PMID- 14694677
TI  - Diagnosis of pneumonia.

PMID- 14694678
TI  - Opening Pandora's box.

PMID- 14694679
TI  - Breach of confidentiality?

PMID- 14694680
TI  - Definition of diabetes mellitus.

PMID- 14694681
TI  - Recruitment strategies for research.

PMID- 14694682
TI  - Homelessness and primary care.

PMID- 14694683
TI  - Special non-clinical interests as career development.

PMID- 14694684
TI  - Primary care is cost-effective care.

PMID- 14694685
TI  - SARS revisited.

PMID- 14694686
TI  - The future of academic primary care.

PMID- 14694687
TI  - Risk management in general practice.

PMID- 14694688
TI  - War or health?--humanitarian crisis worsens in war-torn Congo.

PMID- 14694689
TI  - Personpower planning.

PMID- 14694690
TI  - A murky future for academic primary care.

PMID- 14694691
TI  - Racism and general practice--time to grasp the nettle.

PMID- 14694692
TI  - 'I saw a great star, most splendid and beautiful': headache in primary care.

PMID- 14694693
TI  - Qualitative study of young people's and parents' beliefs about childhood asthma.
AB  - BACKGROUND: Asthma continues to be a common childhood chronic illness managed
      principally in primary care. Self-management requires co-ordinated efforts of
      young people, carers and health professionals. Non-compliance occurs even when
      parents are supervising care, suggesting that decisions are made on the basis of
      beliefs that contrast with professional advice. Health professionals therefore
      need to understand the views of parents (or other carers) and patients to promote
      good self-management. Little attention has been given to carers' and young
      people's perspectives on asthma. AIM: To gain insights into the beliefs of a
      group of 25 young people aged nine to 16 years old and their carers about asthma
      and its management. DESIGN OF STUDY: Qualitative study using conversational-style
      interviews. SETTING: Generally deprived urban areas of Greater Manchester.
      METHOD: Interviews were conducted with 25 young people with asthma and separately
      with their carers. The interviews were analysed using the principles and
      procedures of grounded theory. RESULTS: Carers reported assessing asthma symptoms
      through observed effects on the child and other family members, including
      emotions and behaviours that disrupted family life. Young people emphasised the
      effect of asthma on their everyday lives and in particular the extent to which
      they appeared different to their peers. Some young people reported continuing
      symptoms and restrictions of activity that differed widely from the reports of
      their carers. CONCLUSION: Differences between young people's and carers' criteria
      for assessment suggest explanations for some 'non-compliant' behaviour. Carers'
      assessment of asthma severity through the absence of acute attacks is consistent
      with managing asthma as intermittent acute episodes. Professionals should take
      account of differences between young people's, carers' and professionals'
      perceptions of asthma.

PMID- 14694694
TI  - A case-control study on the effect of hormone replacement therapy on ischaemic
      heart disease.
AB  - BACKGROUND: Many clinicians believe that hormone replacement therapy (HRT)
      protects against coronary heart disease (CHD) in women. However, recent reports
      have cast some doubt on this because of lack of dose-response or duration
      response effects. Since CHD is common in women--about half of all postmenopausal
      women will get it and about a third of these will die from it--the effect of HRT
      on CHD is of great public health importance. AIM: To determine the degree of
      cardioprotection conferred by HRT, including the effect of duration, time since
      last issue, the addition of progestogens, route of administration, and dose.
      DESIGN: Population-based case-control study. SETTING: Nine general practices
      recruited from the Trent Focus Collaborative Research Network. METHOD: A total of
      417 female cases with CHD matched by age and practice to 2435 controls with a
      case-control ratio of 1:5.8 were studied. The main outcome measure was the odds
      ratio for CHD calculated by conditional logistic regression adjusted for
      diabetes, hypertension, body mass index, and smoking. RESULTS: No evidence was
      found, either from univariate analysis or multivariate analysis, that use of HRT
      was associated with reduced risk of CHD (odds ratio = 1.32; 95% confidence
      interval = 0.93 to 1.87). Indeed, the trend was in the opposite direction. There
      was no association for different types of HRT (opposed or unopposed) or routes of
      administration. Similarly, there was no association for current or past use and
      no effect for dose or duration. CONCLUSION: This study adds to growing evidence
      that HRT does not confer cardioprotection. Until there is robust evidence to the
      contrary, general physicians need to assess risks and benefits of HRT
      independently of any possible reduction in risk of CHD.

PMID- 14694695
TI  - A cluster randomised controlled trial of patient-held medical records for people
      with schizophrenia receiving shared care.
AB  - BACKGROUND: Patient-held records can improve communication across the primary
      secondary interface. There has been no previous rigorous assessment of the
      utility of patient-held records for people with schizophrenia from a primary care
      perspective and their value for this population is unclear. AIM: To evaluate the
      effectiveness of a patient-held record for patients with schizophrenia receiving
      shared care. DESIGN OF STUDY: Cluster randomised controlled trial. SETTING:
      Seventy-four general practices and six community mental health localities in
      Birmingham, England between June 1998 and June 1999. METHOD: A sample of 201
      patients with schizophrenia (ICD-10 classification F20) was recruited; of these,
      100 were intervention and 101 were control. Patient-held records were given to
      the intervention patients. At 12-month follow-up, all patients were accounted for
      and 191 (95%) were revisited. Primary outcomes were the Verona Service
      Satisfaction Scale-54 (VSSS-54) and the Krawiecka and Goldberg (K & G) rating
      scale of psychopathology at 12-month follow-up. Secondary outcomes were use of
      primary and secondary care services. RESULTS: A total of 63/92 (68.5%) patients
      still had the patient-held record, 64/92 (69.6%) had used it, and 39 (60.9%) of
      the 64 who had used it said the patient-held record was regularly used by their
      keyworker. However the patient-held record had no significant effect on primary
      outcomes (VSSS-54: F1,116 = 0.06, P = 0.801, K & G: F1,116 = 0.6, P = 0.439) or
      on use of services. A higher symptom score was associated with not using the
      patient-held record. CONCLUSIONS: The trial provides no good evidence to suggest
      that patient-held records should be introduced as part of routine shared care for
      all patients with schizophrenia. However, the patient-held record was acceptable
      to patients with schizophrenia and acted as a communication tool, particularly
      between patients and keyworkers.

PMID- 14694696
TI  - Electronic transfer of prescription-related information: comparing views of
      patients, general practitioners, and pharmacists.
AB  - BACKGROUND: The National Health Service (NHS) intends to introduce a system of
      electronic transfer of prescription-related information between general
      practitioners (GPs) and community pharmacies. The NHS Plan describes how this
      will be achieved. AIM: To gather opinions of patients, GPs, and community
      pharmacists on the development of a system of electronic transfer of prescription
      related information between GPs and community pharmacies. DESIGN OF STUDY: Survey
      combining interviews, focus groups, and postal questionnaires. SETTING: General
      practitioners, opinion leaders, computing experts, pharmacists, and patients.
      Eight hundred members of the public, 200 GPs, and 200 community pharmacists, all
      living in Scotland. METHOD: Content-setting interviews and focus groups were
      conducted with purposive samples of relevant groups. Postal questionnaires were
      developed and sent to random samples of members of the public selected from the
      electoral roll, GPs, and community pharmacists. RESULTS: The corrected postal
      response rates were: 69% (patients); 74% (GPs); and 74% (community pharmacists).
      All three groups were generally supportive of electronic transfer of prescription
      related information. Different aspects appealed to each group: patients
      anticipated improved convenience; GPs, better repeat prescribing; and
      pharmacists, an enhanced professional role. Security of patient-identifiable
      information was the main concern. All groups acknowledged potential benefits of a
      full primary care information system, but GPs and patients had reservations about
      allowing community pharmacists to access parts of the medical record that did not
      concern medication. CONCLUSION: Electronic transfer of prescription-related
      information is likely to be acceptable to all users, but concerns about patient
      confidentiality and an extended role for pharmacists in prescription management
      need to be addressed.

PMID- 14694697
TI  - Children who suffer from headaches--a narrative of insecurity in school and
      family.
AB  - BACKGROUND: Headaches are common among schoolchildren, who seem to be afflicted
      increasingly. AIM: To analyse children's descriptions of their headaches and
      their thoughts about them, it being assumed that children have insight into the
      conditions that affect their health. DESIGN OF STUDY: Interview study. SETTING:
      Two state schools in the city of Malmo, Sweden. METHOD: Fourteen children aged
      between ten and 12 years, who had gone to the school nurse more than once during
      the previous two-month period complaining of a headache, took part in
      thematically structured interviews. Qualitative analysis was performed, aimed at
      identifying the basic themes involved. RESULTS: The children were found to
      consistently associate their headaches with conditions in school, specifically
      with more theoretically-oriented subjects (maths or Swedish), a noisy and
      disorderly school environment, and insecure relations with classmates. The second
      theme they took up was insecurity or conflict within the family. Reports of this
      constituted a major part of the children's accounts of their life situation,
      despite their failing to link such matters with their headaches. Many of the
      children considered their patterns of reacting, such as feeling unable to cope or
      becoming angry, as contributing to their getting headaches. CONCLUSIONS: The
      children related their headaches consistently to everyday situations and to their
      relations with others. This highlights the need for broadening the consultation
      in terms of including personal and contextual factors.

PMID- 14694698
TI  - Child psychiatric disorders among primary mental health service attenders.
AB  - The aim of this study was to establish the range of psychiatric disorders and
      psychiatric comorbidity among children and adolescents attending a primary mental
      health service (PMHS). The main psychiatric diagnostic categories were:
      oppositional defiant disorders (ODDs) (75.3%), anxiety disorders (36.1%), mood
      disorders (35.1%), and attention deficit hyperactivity disorders (ADHDs) (28.9%).
      The study found high rates (61.8%) of psychiatric comorbidity. It concludes that
      training in the recognition of likely psychiatric comorbidity in this population
      is essential for professionals working in the interface between primary and
      specialist services.

PMID- 14694699
TI  - Communication at the interface: do better referral letters produce better
      consultant replies?
AB  - A study of the quality of 637 referral letters from general practitioners (GPs)
      and corresponding reply letters from medical specialists showed that both types
      of letters can be improved, and that specific requests by GPs were addressed
      explicitly by the specialists in only a limited number of cases. Better referral
      letters resulted only partly in better reply letters. A letter is considered to
      be of higher quality when a specialist commences a letter with a reference to the
      specific request by the GP. In conclusion, opportunities for optimal
      communication should be better used.

PMID- 14694700
TI  - Patient self-monitoring of blood pressure in general practice: the 'inverse white
      coat' response.
AB  - Self-monitoring of blood pressure may give a truer estimate of usual blood
      pressure than readings by a doctor in the surgery, and may save time for health
      professionals. This study aimed to determine the accuracy of self-monitoring in
      the surgery using a wrist oscillometric sphygmomanometer (Omron RX). One hundred
      and seventy-three patients were taught to record their own blood pressure with
      the Omron RX. One hundred and nineteen patients recorded three self-measurements
      at monthly intervals, and their readings were compared with those of an
      experienced nurse using the Omron RX and a mercury sphygmomanometer. On average,
      patients' readings were higher than the nurse's readings (mean difference in
      phase 1 = systolic pressure 4.7 +/- 13.1 mmHg, diastolic pressure 2.7 +/- 9.3
      mmHg [both P < 0.001]). Only half of the patients' readings were within 10 mmHg
      systolic and 5 mmHg diastolic of the nurse's readings. The readings by the nurse
      using both devices did not differ.

PMID- 14694701
TI  - Attention-deficit hyperactivity disorder.
AB  - Attention-deficit hyperactivity disorder (ADHD) affects between 1.4% and 6% of
      children. The importance of the role of primary care in the recognition and joint
      management of this disorder is being increasingly highlighted. Despite a wealth
      of research, the diagnosis and management of ADHD have attracted a good deal of
      controversy. In this discussion paper, we focus on the empirical basis for some
      of the more controversial aspects of ADHD, such as diagnosis (discussing both
      under- and overdiagnosis), aetiology, outcomes, and the role of psychosocial
      factors in this disorder. We conclude that, provided the diagnosis of ADHD is
      made accurately and systematically, there are no good scientific grounds for
      dismissing the concept of ADHD or for failing to intervene.

PMID- 14694703
TI  - Cancer prevalence and infrequent consulters.

PMID- 14694702
TI  - Beyond somatisation: a review of the understanding and treatment of medically
      unexplained physical symptoms (MUPS).
AB  - Patients commonly present in primary care with symptoms for which no physical
      pathology can be found. This study is a review of published research on medically
      unexplained symptoms (MUPS) in primary care. A literature review and qualitative
      comparison of information was carried out. Four questions were addressed: what is
      the prevalence of MUPS; to what extent do MUPS overlap with psychiatric disorder;
      which psychological processes are important in patients with MUPS; and what
      interventions are beneficial? Neither somatised mental distress nor somatisation
      disorders, based on symptom counts, adequately account for most patients seen
      with MUPS. There is substantial overlap between different symptoms and syndromes,
      suggesting they have much in common. Patients with MUPS may best be viewed as
      having complex adaptive systems in which cognitive and physiological processes
      interact with each other and with their environment. Cognitive behavioural
      therapy and antidepressant drugs are both effective treatments, but their effects
      may be greatest when the patient feels empowered by their doctor to tackle their
      problem.

PMID- 14694704
TI  - Diagnostic ability among non-psychiatrists.

PMID- 14694705
TI  - Do medical students want to become GPs?

PMID- 14694706
TI  - Macroscopic haematuria and urological cancer.

PMID- 14694707
TI  - Macroscopic haematuria and urological cancer.

PMID- 14694708
TI  - The video component of the MRCGP examination.

PMID- 14694709
TI  - What's in a word?

PMID- 14694710
TI  - Recruitment in general practice.

PMID- 14694711
TI  - Qualitative survey on nursing and residential homes.

PMID- 14694712
TI  - Time to counter 'fever phobia'!

PMID- 14694713
TI  - An oral history of general practice. 10: Diagnostics and therapeutics.

PMID- 14694714
TI  - GP pay--naming the elephants.

PMID- 14694715
TI  - [Effects of oral cadmium exposure on expression of metallothionein-I and
      metallothionein-II mRNA in rat prostate].
AB  - OBJECTIVE: To investigate the possible effects of oral cadmium(Cd) exposure on
      the expression levels of metallothionein-I and metallothionein-II (MT-I and MT
      II) mRNA and the distribution of zinc (Zn) and Cd in rat prostate. METHODS:
      Cadmium was given to rats at doses of 50, 100, and 200 mg/kg in drinking water.
      The contents of Zn and Cd in prostate were measured by atomic absorption
      spectrometry(AAS), and the levels of MTs mRNA were determined by RT-PCR. RESULTS:
      After Cd administration, the content of Zn was decreased in both the ventral and
      the dorsolateral lobes of rat prostate. In 200 mg/kg Cd group, the contents of Zn
      in ventral prostate were 9.5 and 8.5 micrograms/g wet weight respectively after
      one month and six months, which were significantly lower than those of
      control(17.0 and 18.9 micrograms/g wet weight). In contrast, the contents of Cd
      in both ventral and dorsolateral lobes of prostate significantly increased with
      the increasing dose and time of Cd administration. It was also noted that Cd
      administration resulted in a significant down-regulation of the expression of MT
      I and MT-II mRNA in rat ventral prostate. In 200 mg/kg Cd group after one and six
      months, the relative expression levels of MT-I (0.410, 0.339 respectively) and MT
      II (0.100, 0.112 respectively) were significantly lower than those of MT-I
      (0.760, 0.830 respectively) and MT-II (0.429, 0.439 respectively) in control
      group. CONCLUSION: Oral Cd exposure could influence the distribution of Zn and
      the expression levels of MTs mRNA in rat prostate.

PMID- 14694716
TI  - [Study on the difference in DNA damage of human lymphocyte caused by arsenicals].
AB  - OBJECTIVE: To explore whether there is difference in arsenicals-induced DNA
      damage of human lymphocyte. METHODS: Lymphocyte were sterilely collected from
      healthy donor and exposed to sodium arsenite (AsIII), sodium arsenate(AsV) and
      methyl sodium arsenate(MAsv) at 1,5,10,20 and 50 mumol/L. After incubation of 24
      hours, cells were collected by centrifugation and DNA damage was detected by
      single cell gel electrophoresis (SCGE). RESULTS: The comet frequency distribution
      of all groups except 1 mumol/L group of MAsV were significantly different from
      that of control. The comet length of all groups except 1 mumol/L group of AsV and
      1.5 mumol/L groups of MAsV were significantly higher than that of control. There
      were correlations between the doses of arsenicals and the ratios of comet cell or
      length of comet(rAsIII = 0.8134, rAsV = 0.8734, rMAsV = 0.8994). CONCLUSION: DNA
      damage in human lymphocyte were induced by all the three arsenicals. A dose
      effect relationship was observed between exposure doses of the same arsenical and
      DNA damage. With different arsenicals but the same exposure dose, the DNA damage
      level was as follow: AsIII > AsV > MAsV.

PMID- 14694717
TI  - [The antagonism of rhizoma gastrodiae to lead-induced damage of hippocampus in
      rats].
AB  - OBJECTIVE: To observe and explore the antagonism of rhizoma gastrodiae (RGT) to
      the impairment of learning and memory ability induced by lead in rats. METHODS:
      36 Wistar rats were randomly divided into 3 groups, 12 rats in every group, (1)
      control group: treated with distilled water; (2) lead group: treated with lead
      acetate (0.1 g.kg-1.d-1); (3) lead-RGT group: lead acetate (0.1 g.kg-1.d-1) +
      RGT(4.0 g.kg-1.d-1). The ability of learning and memory of the rats was measured
      monthly by swimming test; 3 months later, the rats were decapitated and nitric
      oxide(NO) and total antioxidative capacity(TAOC) in hippocampus were measured
      immediately and the examination for pathology was also made. RESULTS: (1) In
      swimming test, the number of seeking for anchorage in lead group(1, 2, 3 month:
      10.10 +/- 1.10, 7.80 +/- 1.32, 5.40 +/- 0.97 respectively) were significantly
      decreased, compared with the control(P < 0.01); the number of seeking for
      anchorage in RGT-lead group(1, 2, 3 month: 11.90 +/- 0.95, 10.90 +/- 0.95, 9.70
      +/- 0.96 respectively) were significantly increased, compared with lead group(P <
      0.01). (2) NO (0.733 +/- 0.015) mumol/g pro and TAOC (0.945 +/- 0.017) U/mg pro
      in hippocampus of lead group were significantly decreased compared with the
      control(P < 0.01) whereas NO(0.769 +/- 0.021) mumol/g pro and TAOC(0.986 +/-
      0.010) U/mg pro in hippocampus of RGT-lead group were significantly increased
      compared with lead group(P < 0.01). (3) Pathological examination showed that in
      lead group, marked atrophy in hippocampus, cellular denaturation and necrosis,
      dissolution and disappearance in axon were found. In lead-RGT group, the atrophy
      of hippocampus was not obvious, the cell morphology was nearly normal, no obvious
      abnormal changes were seen. CONCLUSION: RGT is antagonistic to the impairment of
      hippocampus and of learning and memory ability induced by lead.

PMID- 14694718
TI  - [The investigation on the changes of haematological parameters in the
      occupationally lead exposed workers].
AB  - OBJECTIVE: To estimate the level of blood lead and some haematological parameters
      in the workers occupationally exposed to lead so as to know the effect of lead
      exposure on hematopoietic system in exposed workers. METHODS: The graphite
      furnace atomic absorption spectrocopy was used to determine blood lead (BPb). The
      haematological parameters were determined by Sysmex KX-21 automated haematology
      analyzer. RESULTS: Hemoglobin (Hb) in the lead-absorption group[male: (129.3 +/-
      12.3) g/L, female: (112.2 +/- 9.4) g/L], and hematocrit (HCT) in the lead
      absorption group[male: (0.338 +/- 0.030) L/L, female: (0.302 +/- 0.028) L/L] were
      significantly lower than those in normal people group and lead-exposed group (P <
      0.05, P < 0.01). The relationships between BPb and Hb, HCT were weakly negative
      correlation. Red cell distribution width (RDW) in the lead-absorption group(male:
      16.68% +/- 0.80%, female: 16.98% +/- 0.98%) were significantly higher than those
      in normal people group and lead exposed group, and RDW in lead exposed group
      (male: 14.77% +/- 0.83%, female: 14.92% +/- 1.13%) were higher than that in
      normal people group. BPb was weakly positively correlated with RDW. CONCLUSION:
      Hb, HCT and RDW were three indices which may reflect the occurrences and degrees
      of anaemia in lead exposed workers.

PMID- 14694719
TI  - [Evaluation of the effect of intervened measures for health behavior of lead
      exposed workers].
AB  - OBJECTIVE: To intervene the health behavior of lead exposed workers by setting
      down and implementing a series of measures and evaluating the effects of these
      measures so that the occupational lead poisoning would be decreased. METHODS: 105
      lead exposed workers in a factory were chosen as subjects. Blood lead
      concentration and rate of cognition on relevant health knowledge were examined
      before and after intervened measures. RESULTS: The cognition rate raised from
      56.6% to 97.3% after training. Lead concentration in blood decreased by 17.7% (t
      = 4.10, P = 0.000) and delta-ALA in urine decreased by 23.9% (t = 4.248, P =
      0.000) 12 months after intervention. The prevalence of occupational lead
      absorption and poisoning also decreased. The number of workers with blood lead
      content > 2.41 mumol/L was decreased from 6 to 3, and > 1.93 mumol/L from 14 to
      10. CONCLUSION: To develope occupational health promotion, enhance health
      education and improve health behavior are the effective way to prevent from
      occupational lead poisoning.

PMID- 14694720
TI  - [Relation of genetic polymorphism of NQO1 and GSTT1 with risks of chronic benzene
      poisoning].
AB  - OBJECTIVE: To explore the relation between genetic polymorphisms of NQO1, GSTT1
      and risks of chronic benzene poisoning (BP). METHODS: A case-control study was
      conducted. 152 BP patients and 152 workers occupationally exposed to benzene
      without poisoning manifestations were investigated. Polymerase chain reaction
      (PCR), denaturing high-performance liquid chromatography(DHPLC) and sequencing
      were used to detect the single nucleotide polymorphisms(SNPs) of the promoter and
      complete coding-region of NQO1 gene. Multiple PCR was used to detect GSTT1
      genotype. RESULTS: In smoking population, there was 7.73-fold (95% CI: 1.71
      34.97, P = 0.010) of risk in BP subjects carrying NQO1c. 609 T/T genotype,
      compared with those carrying C/C and C/T. genotype. In drinking population, the
      individuals carrying the 6th extron of NQO1c. 609 T/T homozygote genotype had a
      11.00-fold(95% CI: 1.89-63.83, P = 0.005) risk of BP compared to those with
      NQO1c. 609 C/T and C/C genotypes. CONCLUSION: The subjects carrying NQO1c. 609
      T/T genotype and together with the habit of smoking or drinking may be more
      susceptible to BP.

PMID- 14694721
TI  - [Acute fluoroacetamide poisoning with main damage to the heart].
AB  - OBJECTIVE: To observe the heart damage in 10 patients with acute fluoroacetamide
      poisoning. METHODS: Monitoring serum activities of myocardial enzymes [creatine
      kinase (CK), asparate aminotransferase (AST), lactate dehydrogenase(LDH) and
      hydroxybutyrate dehydrogenase(HBDH)] and recording ECG on these 10 patients were
      performed during the period of their hospitalization. In the mean while, 24 hour
      dynamic ECG were also recorded and analysed using GP7000L Holter. RESULTS: (1)
      Urinary fluorine ion concentrations were increased in 9 patients before therapy
      and in all these 10 patients during therapeutic period. (2) The activities of
      serum CK in 2 patients and that of serum HBDH in one patient were increased
      before therapy. However, the serum activities of one or more than one myocardial
      enzymes were increased in all these 10 patients during therapeutic period. (3)
      Four patients had abnormal change of ECG before therapy and 5 patients during
      therapeutic period. (4) 24 hour dynamic ECG records showed that there were heart
      electrical alternans in 9 patients. One patient had wandering pacemaker and 6
      patients had arythmia. CONCLUSION: Fluoroacetamide may cause obvious heart
      damage, and also heart electrical alternation.

PMID- 14694722
TI  - [A study on the adduct characteristics of styrene and DNA].
AB  - OBJECTIVE: To explore the adduct characteristics of styrene and DNA. METHODS: The
      adduct reactions between styrene, urinary mandalic acid(MA), phenylglyoxalic
      acid(PGA), mercapturic acid of styrene (UMA) and DNA were studied by ultraviolet
      spectral analysis. The SO-DNA adducts by 32P-post labeled method, the chemical
      structures of SO-DNA adducts by GC-MS and NMR were also studied. RESULTS: SO
      combined with DNA at O6, N2 positions of dGMP to form six adducts, but styrene,
      urinary mandalic acid, phenylglyoxalic acid and mercapturic acid of styrene did
      not react with DNA to form adduct. CONCLUSIONS: Styrene formed adduct with DNA
      through its active center metabolite--SO after entering the body. SO combined
      with DNA at O6, N2 positions of dGMP to form adducts. If these DNA adducts are
      not repaired or are mis-repaired before cell duplication, the gene mutation and
      chemical damage would happen. No adduct reactions are seen among other
      metabolites of styrene.

PMID- 14694723
TI  - [The changes of soluble interleukin-2 receptor in serum and cerebrospinal fluid
      of patients with delayed encephalopathy after acute carbon monoxide poisoning].
AB  - OBJECTIVE: To explore the changes of soluble interleukin-2 receptor(sIL-2R) in
      serum and cerebrospinal fluid (CSF) of patients with delayed encephalopathy after
      acute carbon monoxide poisoning (DEACMP). METHODS: There were 31 patients with
      DEACMP, 32 patients with other encephalopathy and 31 controls in this study. The
      levels of sIL-2R in serum and CSF were detected by ELISA. RESULTS: Serum sIL-2R
      in patients with DEACMP[(329.21 +/- 160.99)U/ml] was significantly higher than
      that in control[(115.67 +/- 89.58) U/ml, P < 0.05)], but not significantly
      different from that in the other encephalopathy group[(367.50 +/- 123.14) U/ml, P
      > 0.05)]. CSF sIL-2R in patients with DEACMP[(54.48 +/- 43.04) U/ml] measured a
      little before discharge was significantly lower than that in patients with the
      other encephalopathy[(110.24 +/- 76.56) U/ml, P < 0.05)], but not significantly
      different from that in the control group[(34.96 +/- 22.70)U/ml, P > 0.05)]. At
      the pre-discharged period, CSF sIL-2R in patients with DEACMP[(100.26 +/- 93.65)
      U/ml] was significantly higher than that at the early stage of
      hospitalization[(52.28 +/- 43.31) U/ml, P < 0.05)]. No significant difference in
      serum sIL-2R was found between early stage of hospitalization[(338.34 +/- 161.53)
      U/ml] and pre-discharge [(351.31 +/- 175.93) U/ml, P > 0.05)]. CONCLUSION: The
      occurrence of DEACMP may be related with immunopathological damage. The sIL-2R
      levels in serum and CSF may give information about the state of immunological
      function of the patients with DEACMP and may contribute to determining the
      patient's condition and prognosis.

PMID- 14694724
TI  - [Study on DNA damage in rat bone marrow cells induced by mustard gas].
AB  - OBJECTIVE: To study the damage of DNA in rat bone marrow cells induced by mustard
      gas. METHOD: Male SD rats were randomly divided into six groups. Physiological
      saline, propylene glycol and mustard gas(0.2, 0.4, 0.8, 1.6 mg/kg) were given
      separately by i.p. injection. 5 rats in each group were killed after 0, 24, 48,
      72 hours of exposure. The DNA damage in rat bone marrow cells was assayed by
      single cell gel electrophoresis (SCGE). RESULTS: There is no significant
      difference of DNA damage among all groups at 0 h(P > 0.05). The rates of DNA
      migration and the lengths of DNA migration of the rat bone marrow cells in
      propylene glycol group at 24, 48, 72 hours were 15.4% +/- 0.21%, 16.0% +/- 0.19%,
      15.7% +/- 0.23% and (11.4 +/- 0.2), (13.5 +/- 0.3), (12.8 +/- 0.2) micron
      respectively, and they were significantly higher than those of physiological
      saline group at the same time(P < 0.05). The rates of DNA migration and the
      lengths of DNA migration of the rat bone marrow cells in mustard gas groups at
      24, 48, 72 hours were significantly higher than those in physiological saline
      group and propylene glycol group at the same time(P < 0.05). CONCLUSION: Mustard
      gas could induce DNA damage in rat bone marrow cells. The damage was likely to
      rise as the dose increased and was time-dependent.

PMID- 14694726
TI  - [Study on the therapeutic effect of combined use of obidoxime and atropine with
      respiratory machine on respiratory muscle paralysis caused by omethoate poisoning
      of rats].
AB  - OBJECTIVE: To examine the therapeutic effect of combined use of obidoxime and
      atropine with artificial ventilation on respiratory muscle paralysis caused by
      omethoate poisoning in rats. METHODS: Rats were exposed to 2 times the dose of
      LD50 omethoate and treated with atropine (10 mg/kg) to counteract cholinergic
      symptoms. When the rats' respiratory frequency became slower and breathed with
      difficulty, the trachea intubation and artificial ventilation was carried out.
      The rats in group A were continuously treated with atropine. The dose of
      obidoxime for Group B, C and D were 8, 15, 20 mg/kg respectively, given at the
      same time as artificial ventilation and 1, 2, 3 hours later. The doses of
      atropine was reduced to 1/3 - 2/3 of the first dose so as to maintain the rats
      atropinized. If the rat survival was beyond 60 minutes after withdrawal of
      artificial ventilation, the combined treatment was considered successful. The
      function of isolated phrenic diaphragm of the rats was observed with MS-302
      physiological and pharmacological analysis instrument. RESULTS: None of the rats
      in Group A was successful after withdrawal from artificial ventilation and the
      function of phrenic diaphragm appeared poor; whereas > 80% of the rats in B, C, D
      Group were successful after withdrawal from artificial ventilation in 3 h and the
      function of phrenic diaphragm remained well. The survival rate in B, C and D
      groups were higher after withdrawal from artificial ventilation than that in
      Group A(P < 0.01). The function of phrenic diaphragm in Group B, C and D were
      gradually decreased after ACh was added into the container. CONCLUSIONS: Combined
      use of suitable dose of obidoxime and atropine with artificial ventilation for
      respiratory muscle paralysis caused by omethoate poisoning could promote the
      recovery of diaphragm function and reduce the death rate in poisoned rats.

PMID- 14694725
TI  - [The experimental study of the anti-damage effect of iminoethyl-lysine on noise
      induced cochlea damage in guinea pig].
AB  - OBJECTIVE: To investigate the anti-damage effect of iminoethyl-lysine on noise
      induced cochlea damage in guinea pig. METHODS: 40 healthy red eye guinea pigs
      were randomly divided into 4 groups: Group A, normal control group; Group B,
      noise group; Group C, noise and drug group; Group D, iminoethyl-lysine group.
      Guinea pigs of both group B and group C were exposed to 115 dB white noise for 6
      hours/day for 6 days. Group C and Group D were treated with iminoethyl-lysine(10
      mg/kg) intraperitoneally, while Group B were treated with the same volume of
      physiological saline. ABR hearing threshold was measured in all animals before
      and after experiment. The expression of inducible nitric oxide synthase(NOS II)
      in the cochlea was examined by the method of immunohistochemistry. Also the
      cochlea of four groups were examined with scanning electronic microscope. ABR
      hearing threshold, expression of NOS II and structure of cochlea of four groups
      were compared with each other. RESULTS: There was no significant difference in
      ABR hearing threshold among four groups before the experiment(P > 0.05). There
      was no significant ABR hearing threshold shift in Group A and Group D after the
      experiment(P > 0.05), and there was significant ABR hearing threshold shift in
      Group B and Group C(P < 0.05). After the experiment, the ABR hearing threshold of
      group B(60.23 +/- 11.23) dB, was higher than that of Group C(38.46 +/- 7.24) dB,
      P < 0.05. The expression of NOS II was negative in the cochlea of Group A and
      Group D, but was stronger in Group B than that in Group C. The damage of outer
      hair cells of cochlea of Group B was more severe than that of Group C.
      CONCLUSIONS: The expression of NOS II in the guinea pig's cochlea damaged by
      noise is positive. Iminoethyl-lysine could inhibit the activity of NOS II and has
      the anti-damage effect on noise-induced cochlea damage. It is indicated that
      nitric oxide plays an important role in the pathogenesis of noise-induced hearing
      loss.

PMID- 14694727
TI  - [Study on three kinds of gasoline oxygenates-induced DNA damage in mice
      fibroblasts].
AB  - OBJECTIVE: To study DNA damage of three kinds of gasoline oxygenates. METHOD:
      Single cell gel electrophoresis assay(Comet assay) was used to detect the damage
      effects of three gasoline oxygenates[methyl tertiary butyl ether(MTBE), ethanol
      anhydrous(EA) and dimethyl carbonate(DMC)] on DNA in L-929 mice fibroblasts.
      RESULTS: In certain concentation(37.500-150.000 mg/ml), MTBE could directly cause
      DNA damage of L-929 mice fibroblasts. There was obvious dose-effect relationship,
      i.e. when the concentration of MTBE was increased from 9.375 to 150.000 mg/ml,
      the comet rate also increased from 4% to 85%, and the length of comet tail
      changed correspondingly. The results of EA and DMC were negative. CONCLUSION:
      Under the condition of this experiment(150.000 mg/ml), MTBE could directly cause
      DNA damage while the effect of EA and DMC on DNA damage was not found.

PMID- 14694728
TI  - [A prospective cohort study on the effect of occupational dust exposure and
      smoking on mortality].
AB  - OBJECTIVE: To study the effect of dust exposure and smoking on mortality.
      METHODS: Based on the Guangzhou Occupational Health Surveillance Record System
      established in 1989-1992, 61,648 factory workers, aged > or = 30, occupationally
      exposed to dust and non-exposure to dust or any other hazardous
      substances(controls), were included in a prospective cohort study. RESULTS: (1)
      28 were lost to follow-up. Malignant neoplasm was most common among 1,186 deaths.
      (2) Most subjects were male workers, aged 35 to 44, with secondary education, and
      married. 42.2% had ever smoked and 32.8% were ever-drinkers. (3) To compare with
      non-exposure, non-smoking + non-smoking and non-exposure respectively, the
      adjusted RR of death from all causes, malignant neoplasm and respiratory diseases
      were 1.24, 1.34 and 1.96 respectively for dust exposed workers(compared to
      control, P < 0.01), 1.16, 1.37 and 1.63 respectively for those smoking(compared
      to non-smoker except RR of death from respiratory diseases, P < 0.01), and 1.48,
      1.85 and 3.12 respectively for those smoking and dust exposure, which were far
      greater than those either smoked or exposed to dust alone(P < 0.01). (4) The
      influence of dust exposure on death was mainly showed in occupational exposure to
      silica dust and wood dust. CONCLUSION: Both dust exposure and smoking may
      increase the mortality, and they had synergistic effect.

PMID- 14694729
TI  - [The impact of night work near the day of ovulation on outcome of pregnancy].
AB  - OBJECTIVE: To investigate the effect of night work near the day of ovulation on
      outcome of pregnancy. METHODS: Daily early morning urine samples were collected
      from eligible shift women workers, and human chorionic gonadotropin(hCG),
      follicle-stimulating hormone(FSH), the urinary steroid metabolites of estrogen
      and progesterone(PDG, E1C) were measured to confirm the day of ovulation and
      early fetal loss(EFL). Questionnaires were used to know workshift, other
      occupation exposures, and related information. RESULTS: 12 clinical spontaneous
      abortion(SAB), 18(EFL) and 44 clinical living birth were analyzed in relation to
      SAB, EFL and night shift near the day of ovulation by using single factor and
      multi-factor logistic regression. The result showed that night shift on the day
      of ovulation and the day before or after ovulation was related with SAB both in
      single- and muti-factorial analysis(single factor: OR = 2.48, 95% CI 1.10-5.60;
      multi-factor; OR = 3.90, 95% CI 1.28-11.90). CONCLUSION: Night shift near the day
      of ovulation may be related to SAB.

PMID- 14694730
TI  - [Maria Ivete: eminent person in Brazilian nursing].

PMID- 14694731
TI  - [AIDS in pregnant women: potential to reduce vertical transmission].
AB  - This study is an attempt to investigate the knowledge that pregnant women have
      about vertical transmission, the risk of the fetus, and the significance of the
      seropositive result that identifies her as infected by HIV. The exploratory
      research of a qualitative nature was carried out in Health Units in the city of
      Sao Leopoldo/RS. The analysis captured the perception of 63 pregnant women
      between the ages of 16 and 40 about the reasons and the significance of the test,
      their knowledge and everyday experiences, and the perspectives and care with the
      baby. The results raise an alert for medical professionals in the pre-natal area
      as to their need to meet a complexity of situations that emerge when pregnancy
      occurs with an AIDS patient.

PMID- 14694732
TI  - [Knowledge of mothers about the significance of the PKU test].
AB  - This is a study of a quanti-qualitative nature carried out in a public maternity
      located in the city of Joao Pessoa-PB, having as an objective to investigate the
      knowledge that the mothers have concerning the PKU Test. The sample was made up
      of 110 women who gave birth in this maternity and/or came for pre-natal service
      there. The results showed that 97% of the mothers had heard about the test and
      99% thought that the PKU Test was important. Despite these results, the data
      reveals that the mothers are not aware of its purpose and the importance of the
      PKU Test.

PMID- 14694733
TI  - [Contribution of mental health to the development of the FHP].
AB  - The Family Health Program (FHP) arises as a new strategy for primary and
      secondary health services, including mental health. Based on these
      presuppositions, the objectives of this article are the following: get to know
      the perception of the nurses about FHP, identify difficulties pertinent to the
      promotion of mental health, and investigate the contribution of the psychiatric
      nursing within the FHP. Five nurses were interviewed that work on the FHP teams
      in the city of Passos-MG and the data was submitted and later on the content of
      the interviews was analyzed. The discussions revealed the need for qualification
      of the professionals to work as a team and with the family, while also showing up
      the need to make the help more humane, seen in this context as a pre-established
      activity without a greater involvement between team/community.

PMID- 14694734
TI  - [Conversation: the fundamental nursing care from the perspective of the
      hospitalized patient].
AB  - The study focuses conversation as care that integrates other elements of hospital
      nursing. It had as its objective to analyze conversation as an essential stage of
      the dialogue between the patient and the nursing team. Five people participated
      who had already been hospitalized and that were now under clinical monitoring due
      to learning to live with AIDS. The information was obtained by means of the
      "Almanac" technique of sensitivity and creativity, semi-structured interview, and
      by active observation. The study contributed to reinforce the relational nature
      of the nursing care and the position of the patient as an object of this care who
      expresses his/her requests and wants in the process of dialoguing between this
      person and the nursing staff, expressed by conversation, which is viewed as a
      significant factor in nursing care.

PMID- 14694735
TI  - [Care during postpartum "confinement." Beliefs and taboos in a group of puerperal
      women].
AB  - In our milieu, postpartum confinement is surrounded by cultural manifestations
      and taboos which are based on natural, supernatural, and social interpretations.
      This work has identified the meanings attributed to self-care by puerperae under
      the theoretical framework of culture. The subjects were women soon after
      childbirth who attended health units with their children for routine procedures.
      The results showed that the beliefs revealed a symbolic power in the
      infrastructure of conducts and behaviors of these women in relation to
      manifestations and care during the postpartum stage. It is important that health
      professionals incorporate the values and beliefs of women soon after childbirth
      into their practice, thus sharing the knowledge involving puerperium and favoring
      the critical understanding of reality and the promotion of health for mothers and
      their children.

PMID- 14694736
TI  - [Nursing in the light of family relations problems].
AB  - The objective is to present some aspects of the family relationship due to
      communication problems. It is a part of a three generation qualitative study
      about the experience of families as they raise their children. The historical
      method was adopted as the methodological line and in the collection of data, in
      association of the participant observation of life history. The existence of
      problems/difficulties were identified in family communication within the scope of
      intra- and inter-generation, as well as changes in this communication throughout
      the three generations with respect to form, quality, quantity, types, resources,
      and others. The conclusion is that there are many problems/difficulties in
      communication within the family, especially within the inter-generation sphere,
      and nursing staff should be aware to these issues if a global assistance is
      intended for the family.

PMID- 14694737
TI  - [Neonatal nursing: analysis of publications indexed in computerized databases].
AB  - The aim of this study was to identify and analyze the production of scientific
      knowledge in the area of neonatal nursing by using table of contents of
      computerized databases. This quantitative, descriptive study took as its source
      of information the MEDLINE, CINAHL, and LILACS databases between 1990 and 2000.
      The titles entered were "neonatal nursing" when accessing the first two databases
      and "neonatal nursing and neonatal nurse" with LILACS. This process identified
      3,576 publications, 2,336 (61.12%) indexed in the CINAHL, 3,062 (85.58%) included
      in North American and English periodicals. Of the total of publications, 1940
      were analyzed and the caring process was the theme with the greatest number of
      publications--804 (41.45%).

PMID- 14694738
TI  - [Participation and autonomy of mothers in the care of the hospitalized child].
AB  - This is a qualitative study whose purpose was to check with mothers the meaning
      and significance of remaining in the hospital and their participation and
      autonomy in the care of the hospitalized child. The field research was carried
      out through participant observation and through interviews with mothers. The
      inclusion of the mother in the care of the child has been taking place in a
      subtle way, and the mother has been taking on procedures which nurses were
      formerly in charge of, concentrating information about the therapeutic process.
      Nurses establish a hierarchical relation of domination-subordination with the
      mothers, who create some autonomy breaks in everyday situations. The lack of a
      collective therapeutic project in a perspective of care focused on the family is
      one of the obstacles to the involvement of the mother in the assistance.

PMID- 14694739
TI  - [Labor and birth: understanding the nurse insertion possibilities].
AB  - This has the objective of understanding the insertion of the nurse in the
      proposals and public policies of assistance in the birthing process. It has a
      qualitative nature, phenomenological approach and uses as sources official
      documents, nursing periodicals, books, and newspapers. The hermeneutic process
      revealed that the nurse's role occurred as occupation characterized by repeated
      actions focused on reducing the mother-child mortality rate. However, the vision
      of this reality made it possible for the professionals and researchers to find
      ways that would allow a re-insertion of the nurse sustained by a scientific
      knowledge and effective practices such as curricular changes, emphasis on the
      legality of the professional practice, and demands for human resource polices
      from the various governmental authorities. All of these happenings give us the
      understanding of an ambiguous course in which the obstetric nurse looks to public
      opinion for orientation in a projecting of herself to other possibilities more
      typical of her professional action.

PMID- 14694740
TI  - [Nursing process: sequences in care make a difference].
AB  - The emphasis of this qualitative investigation was to get to know the
      significance system, its values and beliefs through the male nurse's perspective
      in his confrontation with the new methodological proposal of care in a Hospital
      Institution. Ethnographic interview and data analysis, which was fundamental in
      James Spradley's studies, were the methods used for collecting data. From data
      immersion and inventory approach immerged the following theme: "Sequence in care
      makes the difference", which constitutes the main purpose of this study,
      providing us with opportunities to reflect about and reveal an activity that up
      until now ha been nebulous and reticent in the Brazilian nursing scenario. In
      this way, the male nurses are taken into a perspective concerning the
      understanding and action of the methodology of assistance.

PMID- 14694741
TI  - [A reading of the recent socialized scientific production of REBEn].
AB  - The article results in a first approach to the state-of-the-art research in
      nursing in Brazil. It is part of a research that will analyze other two indexed
      periodicals. It is based on 250 summaries and footnotes of Revista Brasileira de
      Enfermagem REBEn (Brazilian Periodical of Nursing) in the last five years,
      beginning in 1997. The information was segmented and distributed into tables. Our
      tentative conclusion is that there was a predominance of research articles with
      certain homogeneity on the themes covered, a tendency toward collective
      production, predominance of the public universities in the production of
      knowledge, as well as public organs in the financing of the studies. In our
      evaluation, REBEn has become an important means of socialization of knowledge
      production in nursing.

PMID- 14694742
TI  - [Maternal experiences at the intensive care unit: a phenomenological experience].
AB  - This is a phenomenological research in Martin Heidegger's perspective with eight
      mothers staying with their babies in the hospital, with the aim of understanding
      their maternal feelings at the ICU of the Albert Sabin Infant Hospital in
      Fortaleza-CE. The information was obtained by means of phenomenological
      interviews with the following probing question, "What is it like for you as a
      mother to be in an ICU and at the same time follow all that goes on in the
      hospital unit?" and submitted to the analysis of the phenomena sited as proposed
      by Martins and Bicudo. The experiences of the mothers revealed safety and feer,
      hope and anguish, potentialities and impotence, existential concerns and
      expectations of a human being in the world. Beyond these aspects, the mothers
      showed themselves to be authentic people that got free of the occupation and deal
      with the pre-occupation.

PMID- 14694744
TI  - [The fairy tale and modern paternity].
AB  - The study presents the interpretation of a hospital delivery from the male's
      perspective, according to the cultural experiences of the individual, making
      available the simultaneous discovery of that which conceals and brings out this
      phenomenon. In seeking answers to the hidden meanings of the paternity process,
      it points to a literary path of meaning and art: the allegory. The account of the
      material analyzed is presented in the form of a seemingly ingenuous narrative--a
      fairy tale--with a symbolic nature and a moral backdrop, using the fable of
      Charles Perreaut entitled "Little Red Ridding Hood". From this other view, the
      beauty of the modern world is captured, offering a key for interpretations of the
      human realities.

PMID- 14694743
TI  - [Archaeology and genealogy as methodological options of nursing research].
AB  - This article is based on the historical contextualization about the development
      of research in nursing, presents the categories/lines of interest that support
      the human knowledge applied in the Doctorate Thesis in Nursing in Brazil, points
      out the archeological and genealogical methods proposed by Michel Foucault, and
      their possibility to make more difficult the day-to-day tasks of the nursing
      profession Whether in Institutions, Public Policies, Health Reform, and
      Vocational Training, in the attempt to understand which strategies, challenges,
      knowledge base, and practices have influenced the building of the subjects.

PMID- 14694745
TI  - [Caretakers of the elderly and the unified health system].
AB  - This research has the objective of proposing some reflections about the theme of
      people who take care of the elderly, taking as the theoretical, conceptual, and
      political reference the Brazilian public health system. It is broken down into
      four topics. First of all, I attempt to briefly discuss the interfaces of the
      theme Aging and Health with the purpose of laying a theoretical groundwork where
      this is proposed. Secondly, I try to present the Public Health System (SUS) as a
      scenario for the discussion on the issue of taking care of the elderly. Thirdly,
      I present some paradigms about this care as a human attitude and bring to the
      discussion the person who takes care of the elderly. Finally, I present some
      final considerations.

PMID- 14694746
TI  - [Health education for people with glaucoma: approach based on Vygotskiana's
      perspective].
AB  - This study has the objective of discussing the Vygotsky's perspective as a new
      approach for the health education for people with Glaucoma. This theoretical
      model is justified by the possibility it offers for understanding that the person
      is a social being within a process of constant change and transformation. It
      points out theoretical bases for guiding the educational actions, correlating
      them with the importance of recognizing emotions, affections, and the
      potentiality of people as they deal with the illness and learn to take the
      medication.

PMID- 14694747
TI  - [Globalization and the second sex].
AB  - This paper is a reflection which takes as a starting point the process of
      globalization, establishing a counterpoint between the characteristics of this
      process and the propositions of the International Conference on Population and
      Development/1994, aiming at discussing it according to Sen's (2000, 2001)
      writings. This comparative analysis indicates that the discussion about equality
      between the sexes has become more globalized, emphasizing women's situation in
      the contemporary world as an obstacle to development, which was reaffirmed in the
      IV Women's World Convention in 1995. Subsequently, the paper addresses the
      advances occurred in Brazil after the implementations of the propositions of the
      Conference. Finally, it concludes by locating the search of equality between
      sexes in the fields of rights and opportunities as a social necessity strictly
      connected to development.

PMID- 14694748
TI  - [Humanized care for the oncologic patient: reflections with the health team].
AB  - The present study is concerning a practice of assistance built and implemented
      with the health team members of an Oncology and Radiotherapy Service in a large
      general hospital in the east part of the state of Rio Grande do Sul, attempting
      to make the assistance more humane. It was a possibility of reflecting with the
      work team about the assistance provided to the patients in light of the proposals
      of SUS (New Public Health System) and with the perspective of the humanistic
      approach and its methodological proposals.

PMID- 14694749
TI  - ["Defining nursing resources and needs in Brazil" --a document from the 50's in
      the 20th century].
AB  - Describes the document named "Levantamento de Recursos de Necessidades de
      Enfermagem no Brasil" (Defining the Resources Needed in the Field of Nursing in
      Brazil) and makes considerations about its importance to the study of the
      Brazilian Nursing History. This publication is the final report of a research
      accomplished in the fifties and promoted by the Associacao Brasileira de
      Enfermagem with financial help from the Rockefeller Foundation. It contains the
      characterization of the work force in the country and the working conditions of
      vocational schools. It also includes data from the hospitals and public health
      activities. This essay evidences the main data of the report and considers the
      pertinence of similar studies.

PMID- 14694750
TI  - Commonly used herbs.

PMID- 14694751
TI  - Sobering issue. Coming to grips with substance abuse in nursing.

PMID- 14694752
TI  - Can mental and physical activities such as chess and gardening help in the
      prevention and treatment of Alzheimer's? Healthy aging through stimulation of the
      mind.

PMID- 14694753
TI  - The nurse manager in transition.
AB  - With the current, widespread, highly visible, non-fault dismissals brought about
      by massive hospital downsizing and restructuring, there has been a layoff of many
      capable, responsible, and respectable managers. In some localities it will not be
      possible to obtain a similar position to the one that is lost. Adjusting to this
      significant life transition event, moving from one job to another involves a
      process that is initiated when the manager's current reality is disrupted and
      ends when a bridge is built from the disrupted reality to one of the possible
      realities that can be created. During this process there are many emotional ups
      and downs and confusion as to identity. While what is happening may be clear to
      an observer, for the person in transition reality may be fractured in such a
      devastating way that it is like being frozen in time. Finally, a new reality is
      built as the old one is relinquished, and the excitement of new beginnings is
      experienced with a new and perhaps different role. Eventually, the pain and
      disappointment of losing a job is replaced with the challenges of the present.
      Meanwhile, while the present job seems secure it is good planning for the future
      to be aware and ready for the job hunt process. Getting laid off or fired is a
      real possibility in today's tightening economic conditions and the astute nurse
      manager should be ready for it.

PMID- 14694754
TI  - Is there chaos in the brain? II. Experimental evidence and related models.
AB  - The search for chaotic patterns has occupied numerous investigators in
      neuroscience, as in many other fields of science. Their results and main
      conclusions are reviewed in the light of the most recent criteria that need to be
      satisfied since the first descriptions of the surrogate strategy. The methods
      used in each of these studies have almost invariably combined the analysis of
      experimental data with simulations using formal models, often based on modified
      Huxley and Hodgkin equations and/or of the Hindmarsh and Rose models of bursting
      neurons. Due to technical limitations, the results of these simulations have
      prevailed over experimental ones in studies on the nonlinear properties of large
      cortical networks and higher brain functions. Yet, and although a convincing
      proof of chaos (as defined mathematically) has only been obtained at the level of
      axons, of single and coupled cells, convergent results can be interpreted as
      compatible with the notion that signals in the brain are distributed according to
      chaotic patterns at all levels of its various forms of hierarchy. This
      chronological account of the main landmarks of nonlinear neurosciences follows an
      earlier publication [Faure, Korn, C. R. Acad. Sci. Paris, Ser. III 324 (2001) 773
      793] that was focused on the basic concepts of nonlinear dynamics and methods of
      investigations which allow chaotic processes to be distinguished from stochastic
      ones and on the rationale for envisioning their control using external
      perturbations. Here we present the data and main arguments that support the
      existence of chaos at all levels from the simplest to the most complex forms of
      organization of the nervous system. We first provide a short mathematical
      description of the models of excitable cells and of the different modes of firing
      of bursting neurons (Section 1). The deterministic behavior reported in giant
      axons (principally squid), in pacemaker cells, in isolated or in paired neurons
      of Invertebrates acting as coupled oscillators is then described (Section 2). We
      also consider chaotic processes exhibited by coupled Vertebrate neurons and of
      several components of Central Pattern Generators (Section 3). It is then shown
      that as indicated by studies of synaptic noise, deterministic patterns of firing
      in presynaptic interneurons are reliably transmitted, to their postsynaptic
      targets, via probabilistic synapses (Section 4). This raises the more general
      issue of chaos as a possible neuronal code and of the emerging concept of
      stochastic resonance Considerations on cortical dynamics and of EEGs are divided
      in two parts. The first concerns the early attempts by several pioneer authors to
      demonstrate chaos in experimental material such as the olfactory system or in
      human recordings during various forms of epilepsies, and the belief in 'dynamical
      diseases' (Section 5). The second part explores the more recent period during
      which surrogate-testing, definition of unstable periodic orbits and period
      doubling bifurcations have been used to establish more firmly the nonlinear
      features of retinal and cortical activities and to define predictors of epileptic
      seizures (Section 6). Finally studies of multidimensional systems have founded
      radical hypothesis on the role of neuronal attractors in information processing,
      perception and memory and two elaborate models of the internal states of the
      brain (i.e. 'winnerless competition' and 'chaotic itinerancy'). Their
      modifications during cognitive functions are given special attention due to their
      functional and adaptive capabilities (Section 7) and despite the difficulties
      that still exist in the practical use of topological profiles in a state space to
      identify the physical underlying correlates. The reality of 'neurochaos' and its
      relations with information theory are discussed in the conclusion (Section 8)
      where are also emphasized the similarities between the theory of chaos and that
      of dynamical systems. Both theories strongly challenge computationalism and
      suggest that new models are needed to describe how the external world is
      represented in the brain.

PMID- 14694755
TI  - Expression of SR-BI receptor and StAR protein in rat ocular tissues.
AB  - The class-B type-I scavenger receptor (SR-BI) plays a key role in cholesterol
      homeostasis; it mediates the selective uptake of lipoprotein cholesterol to
      steroidogenic tissues. We show by RT-PCR, western blot, in situ hybridization and
      immunohistochemistry analysis that SR-BI is highly expressed in different neuro
      retinal and non-neuronal cells types on rat eye. Immunohistochemistry of the
      steroidogenic acute regulatory protein (StAR) involved in neurosteroid production
      showed the same expression pattern than SR-BI in rat eye. Our results may suggest
      a key role of these genes in the ocular cholesterol metabolism for membranes
      biosynthesis and neurosteroidogenesis.

PMID- 14694756
TI  - [Phytoplankton ecology along the French coasts: inter-site comparison].
AB  - The aim of this study is to characterize the large-scale geographical structures
      of microphytoplankton communities along French coasts. Once the temporal
      variability component shared by all sampled coastal sites was identified, and
      seasonal succession of microphytoplankton communities was described. A between
      site analysis, using multiable comparison methods (STATIS), allowed the
      identification of three large areas according to the temporal variability
      patterns of microphytoplankton populations. The results indicate that the
      hydrodynamic characteristics of the different areas play a major role in the
      geographical structure of microalgal populations in mainland French coastal
      waters.

PMID- 14694757
TI  - Psychoanalysis of death. Introduction.

PMID- 14694758
TI  - Apocalyptic dreams and religious ideologies: losing and saving self and world.

PMID- 14694759
TI  - Who in their right mind wants war? Violence, death, and meaning.

PMID- 14694761
TI  - Laughing at death.

PMID- 14694760
TI  - Fear of death and human destructiveness.

PMID- 14694762
TI  - Buddhism, death, and the feminine.

PMID- 14694763
TI  - Projection and transference in fundamentalist thinking as factors in the
      Holocaust.

PMID- 14694764
TI  - Adaptive insights into death anxiety.

PMID- 14694765
TI  - Freud, death, and creativity.

PMID- 14694766
TI  - [Mechanisms of action of prostaglandin E1 in therapy of peripheral arterial
      occlusive diseases].
AB  - Mode of action of prostaglandin E1 in the treatment of peripheral arterial
      disease. Prostaglandin E1 has been used for the first time in the treatment of
      peripheral arterial occlusive disease 30 years ago. Although widely used, the
      exact mechanism of the known beneficial effects is not completely understood. A
      strong vasodilation is induced after intra-arterial administration of PGE1, but
      is not seen, when PGE1 is intravenously infused. Because of the clinical efficacy
      of intravenously given PGE1, vasodilation is not considered as important mode of
      action. Many effects of PGE1 has been described on cellular factors in the blood,
      hemostasis and fibrinolysis and endothelium. Some of these effects are discussed.

PMID- 14694767
TI  - Thrombin-antithrombin complex and the prothrombin fragment in arterial and venous
      blood of patients with peripheral arterial disease.
AB  - BACKGROUND: Thrombin generation has recently been recognized as an important
      factor in the development of arterial occlusive disease in all vascular
      provinces. Several reports concerning markers of thrombin generation have been
      published with however, conflicting results. It has been demonstrated in vitro
      that accelerated blood flow velocity causes increased thrombin generation via
      higher shear rates. In recent articles TAT and F1 + F2 concentrations are
      reported significantly higher in arterial than in venous blood. A correlation
      with the severity of atherosclerosis or specially with the stage of PAD was
      expected. In the present investigation we additionally collected blood from the
      femoral vein. PATIENTS AND METHODS: In 11 patients with Fontaine stages IIb to IV
      and two healthy subjects TAT and F1 + F2 concentrations were determined in blood
      samples from the femoral artery, the femoral vein (diseased leg) and cubital
      vein. In all cases and at all puncture sites exactly the same atraumatic
      technique of venipuncture was used. RESULTS: The concentrations of TAT and F1 +
      F2 were significantly elevated in patients with PAD. There was no significant
      difference between the concentrations of TAT and F1 + F2 in arterial (femoral
      artery) and venous (femoral vein and cubital vein) blood. CONCLUSION: The results
      from previous investigations have been confirmed only partially. Differences in
      the puncture techniques to collect arterial or venous blood result in an
      increased scattering of the data and a systematic error.

PMID- 14694768
TI  - The reproducibility of the ratio of volume flow in the common femoral vein and
      artery for quantification of the severity of venous insufficiency.
AB  - BACKGROUND: The ratio of volume flow in the common femoral vein and artery
      denoted as venous-arterial Flowindex (VAFI) is significantly increased in venous
      insufficiency according the clinical grade of the disease. This study was done to
      investigate the reliability and reproducibility of VAFI as quantitative pattern.
      PATIENTS AND METHODS: In 43 patients with varicose veins C4-6 EPAS,D,PPR (PVV),
      40 with postthrombotic syndrome C4-6 ESAS,D,PPR,O (PTS) and 48 healthy volunteers
      volume flow in the common femoral vein (VFV) and artery (VFA) were measured by
      duplex. Division of VFV by VFA calculated VAFI. VAFI-measurement was repeated 5
      times at an interval of ten minutes in 63 subjects (23 PVV, 20 PTS, 20 healthy)
      and it was performed at three different days in 68 subjects (20 PVV, 20 PTS, 28
      healthy). RESULTS: Mean VAFI +/- standard deviation was 1.39 +/- 0.26 in PVV,
      1.42 +/- 0.26 in PTS and 0.93 +/- 0.13 in healthy veins (p < 0.001). VAFI
      remained stable and significantly increased (p < 0.001) in PVV and PTS compared
      to healthy veins during 40 minutes and also within three different days.
      CONCLUSION: The venous-arterial flowindex VAFI is a reproducible pattern of the
      hemodynamic severity in venous insufficiency.

PMID- 14694769
TI  - Changes of fascia and muscles before and 12 months after successful treatment of
      recalcitrant venous leg ulcers by shave therapy.
AB  - BACKGROUND: In chronic venous insufficiency (CVI) III typical changes of skin,
      subcutaneous tissue, fascia and muscle can be found. It was believed, that the
      thickening of the fascia is irreversible and it has been postulated that the
      degeneration of muscles is causative for the persistence of recalcitrant leg
      ulcers. PATIENTS AND METHODS: By computed tomography (CT) and magnetic resonance
      imaging (MRI) 8 patients with therapy resistant venous ulcers were examined.
      Changes of fascia and muscles were determined preoperatively and 12 months after
      successful shave therapy. RESULTS: By CT a thinning of the preoperatively
      thickened fascia could be demonstrated in all patients one year after surgery.
      Before shave therapy MRI showed that the fascia was not only thickened and
      blurred, but also had fluid accumulations perifascial. 12 months after therapy
      the fascia was thinner and sharply demarcated. The fluid was either absent or
      distinctively reduced. Referring to the thickness of fascia an average decrease
      of 0.084 cm (0.03-0.17 cm) was observed. Before surgery the muscles showed a
      fatty degeneration as a sign of atrophy; with CT and MRI no changes could be
      demonstrated after one year in all patients. CONCLUSION: The results after one
      year demonstrate for the first time, that the changes of the fascia in CVI III
      are reversible and that there is no direct correlation between the degeneration
      of muscles and the persistence of venous leg ulcers.

PMID- 14694770
TI  - The graft selection for haemodialysis.
AB  - BACKGROUND: In patients with chronic renal failure, a major concern is to provide
      safe and reliable long-term vascular access for haemodialysis. The radiocephalic
      arteriovenous (AV) fistula remains the first choice vascular access procedure,
      however the grafts are used in order to obtain vascular access in patients with
      failed native distal and proximal AV fistulas. The aim of this study was to
      compare the patency rate of different grafts such as standard wall
      polytetrafluoroethylene (sPTFE), bovine vein graft, Diastat graft, in these
      patients. PATIENTS AND METHODS: Four hundred and forty-six AV fistulas were
      surgically created in 361 patients. Eighty-four out of 361 patients undergoing
      different graft replacements were retrospectively reviewed. We evaluated the
      primary patency rates, days between the fistula placement and the last dialysis
      treatment before thrombosis had occurred, and the secondary patency rate, days
      between the fistula placement and the last dialysis treatment before the graft
      was considered completely lost. The graft survival was calculated according to
      the Kaplan-Meier method. RESULTS: There were 58 (69%) women and 26 (31%) men with
      a mean age of 54.5 years. The sPTFE (Gore-Tex) graft was used in 41 (41.8%),
      bovine vein graft (ProCol) in 38 (38.7%) and Diastat vascular grafts in 19
      (19.5%) patients. Primary and secondary patency rates for sPTFE graft were 37%
      and 60%, 68% and 85% for bovine graft and 26% and 42% for Diastat vascular
      grafts, respectively. CONCLUSIONS: This study demonstrates that the bovine vein
      graft provides the longest patency rate compared to the other grafts even in
      patients with multiple failed accesses.

PMID- 14694771
TI  - Spontaneous healing of chylous ascites after abdominal aortic aneurysm repair.
AB  - Postoperative chylous ascites is a rare complication of aortic surgery. This
      report presents a patient with chylous ascites after abdominal aneurysmectomy.
      After a retrospective analysis of full blood count measurements, we observed an
      association between the number of lymphocytes in the patient's total blood count
      and the development and evaluation of chylous ascites. We believe that this
      hypothesis might be helpful, as it suggests that the number of lymphocytes in a
      patient's total blood count may be used as a prognostic factor for the
      development of chylous ascites. Furthermore, our patient appears to be of
      interest from a therapeutical point of view, since repeated therapeutic
      paracenteses alone were sufficient in treating chylous ascites, a finding in
      contradiction to international literature.

PMID- 14694772
TI  - Mycotic aneurysm of the infrarenal aorta.
AB  - The mycotic aneurysms of the infrarenal aorta (MAIA) are extremely rare and the
      associated morbidity and mortality is very high. The classification of infected
      aneurysms considers four types: a) true mycotic aneurysms, b) secondary mycotic
      aneurysms due to bacterial arteritis, c) infected preexisting abdominal aortic
      aneurysms and d) post-traumatic infected false aneurysms. The prognosis of true
      MAIA's is better than the other forms of infected aneurysms. The standard
      treatment includes the resection of the aneurysm and infectious surrounding
      tissues and the restoration of the flow using ex situ (axillobifemoral) bypass or
      in situ replacement with autologous vein or a rifampicinebonded graft. We present
      a case of mycotic aneurysm of the infrarenal aorta and a brief discussion of the
      alternative treatments from the relevant literature.

PMID- 14694773
TI  - Popliteal venous aneurysm, a cause of pulmonary embolism.
AB  - Generally, most aneurysms of the venous system are probably congenital and rarely
      have clinical significance. Popliteal aneurysms are an exception of this rule and
      are known to be a source of recurrent pulmonary emboli. We present a previously
      healthy 42 year old man with multiple pulmonary emboli, diagnosed with a high
      probability lung scan. Venous duplex imaging and magnet resonance imaging showed
      a mass with connection to the popliteal vein of the left knee, suggesting a
      venous aneurysm. Despite therapeutic anticoagulation he suffered further
      pulmonary emboli. After insertion of a temporary vena cava inferior filter
      aneurysm resection and patch reconstruction of the popliteal vein was performed.
      By duplex imaging we proved the patency of the popliteal vein after surgical
      repair. Popliteal venous aneurysms should be kept in mind as possible
      thromboembolic source in young patients with pulmonary embolism. Our review of
      the current literature about popliteal venous aneurysms revealed a high rate of
      pulmonary embolism.

PMID- 14694774
TI  - Christian Doppler is 200 years young.
AB  - Christian Doppler was born 200 years ago in Salzburg, Austria, on November 29,
      1803, worked in Prague and Vienna and died 150 years ago in Venice. In an article
      of eight pages he described the principle, which made him famous. It appeared in
      1842 with the exotic title: "On the Coloured Light of the Double Stars and
      Certain Other Stars of the Heaven". The validity of his principle for velocity
      measurement was confirmed by trumpet sounds produced on a train moving towards
      and away from the observer. Around 1960 Japanese scientists suggested that flow
      velocity in blood vessels could be determined by analysing the difference of
      frequency between emitted and backscattered ultrasound. Rushmer and coworkers
      built machines suitable for medicine in Seattle, where Eugene Strandness
      recognized their potential and applied them in first studies. In 1967 the
      technique jumped to Europe and started to be used worldwide. Already by using
      continuous wave ultrasound it was possible to diagnose occlusive disease of neck
      and limb arteries, venous thrombosis and valvular insufficiency with accuracy.
      Measurements of postestenotic ankle blood pressure were facilitated by Doppler
      sensing. Over the years more sophisticated instruments were developed. Pulsed
      emission of ultrasound waves opened a way to study flow velocity profiles across
      large vessels. By combining the method with A or B mode ultrasound blood flow
      could be quantified and finally perfused segments of blood vessels visualized.
      Duplex scanning in its simple and then in its colour coded version is nowadays
      the standard non-invasive technique that nobody would like to miss. Vascular
      territories like intracranial, renal and intestinal arteries can also be
      explored. For the assessment of microvascular flow in skin and mucosae laser
      Doppler instruments were introduced.

PMID- 14694775
TI  - [DRG-based cost analysis of inpatient conservative treatment of stage III/IV
      peripheral arterial occlusive disease].
AB  - DRG-based cost analysis of inpatient conservative treatment of PAD stage III/IV
      BACKGROUND: In a prospective study carried out by the German Society of Angiology
      and the DRG Competence Center, Munich, the question was investigated whether the
      costs of conservative treatment of patients with PAOD stage III/IV (DRG F65) are
      adequately represented within the current G-DRG system. METHODS UND PATIENTS:
      Between September 1 and December 16, 2002, a total of 704 patients with DRG F65
      (peripheral vascular diseases) were evaluated at 8 angiologic centers in Germany.
      Apart from the length of hospital stay, the total costs (cost equivalents) were
      calculated using a method developed by the DRG Research Group at the University
      of Munster. Moreover, the study population was compared with a German calculation
      sample for the DRGs F65A/B, as published by InEK. RESULTS: As it turned out,
      conservatively treated patients with PAOD stage III or IV (DRGs F65A/B) cause
      significantly (p < 0.001) higher costs and have significantly (p < 0.001) greater
      lengths of hospital stay than patients who were also assigned to DRG F65 because
      of other vascular diseases. At the same time it became clear that angiologic
      centers treat twice as many patients with critical limb ischemia in comparison
      with the German average. The reimbursement hitherto estimated by InEK covers not
      even half the cost actually produced by conservative treatment of PAD stage
      III/IV. CONCLUSION: To ensure a performance-related reimbursement, a new basis
      DRG for patients with PAD stage III/IV has to be created, as has ben proposed by
      the German Society of Angiology. Otherwise, adequate conservative therapy in
      accordance with existing guidelines, of patients who cannot be treated surgically
      or interventionally will not be possible any more in the future.

PMID- 14694776
TI  - [Genetics for the non-geneticist. Semantics and basic facts].
AB  - This chapter is an introduction to a new language, that of genetics. The first
      part recalls and illustrates the elementary concepts of molecular genetics, with
      emphasis on the structure of DNA and the chromosomes, that of genes, the genetic
      code and the genetic factors of sexual differentiation. The second part explains
      medical molecular genetics which is based on a fundamental concept: polymorphism
      of DNA, a normal and physiological phenomenon which arises mostly from genetic
      exchanges which occur during meiosis. Monogenic diseases with mendelian
      transmission may be autosomal dominant or recessive or linked to the X
      chromosome. The understanding of multigenic diseases requires the use of much
      more complex techniques based on so-called "reverse" genetics or on the
      "candidate gene" method.

PMID- 14694777
TI  - [Genetic testing].
AB  - The first genetic tests started to be developed about twenty years ago. Their
      initial applications were limited to genetic counselling and prenatal diagnosis
      of a few hereditary diseases. Technological progress and the identification of
      genes responsible for many hereditary diseases have led to their development and
      diffusion. They have become a nearly irreplaceable tool for the diagnosis of
      hereditary diseases. In the future, their indications should increase when genes
      implicated in multifactorial diseases are progressively identified. The impact
      will probably be particularly important in cardiology because most cardiovascular
      diseases are multifactorial. The first predisposing factors (factor V.
      prothrombin...) for a predisposition to thrombosis are now daily genetic
      investigations. In parallel, the progress in pharmacogenetics should enable
      everyone to have appropriate qualitative and quantitative treatment according to
      their genetic makeups, which should improve both efficacy and safety. In order to
      face up to the exponential increase in demand for the genetic tests which will
      result from these advances, the laboratories should have new high speed, powerful
      and economic equipment. DNA microchips, which are currently under development
      could, at least initially, provide a solution to this problem. It is now certain
      that genetic testing will become routine and, in time, it will be used massively
      in both hospital and community medicine.

PMID- 14694778
TI  - [Genetics and congenital heart diseases].
AB  - We describe in this article the recent data on the genetics of congenital heart
      defects (CHD) organised by type of CHD although each predisposing genetic factor
      is associated with a whole variety of CHD types. The recent progress resulting
      from animal models, molecular cytogenetics and CHD familial cases studies allow a
      better understanding of the determinism of CHD. This lead in term to improved
      counselling of parents of affected children and of CHD adults who would like to
      become parents. Nevertheless, more progress is needed to reach a better accuracy
      in prediction.

PMID- 14694779
TI  - [Hypertrophic cardiomyopathies].
AB  - Hypertrophic cardiomyopathy (CMH) is characterised by hypertrophy of the left
      ventricle, typically predominantly asymmetric on the interventricular septum. The
      dreaded complication of the disease is sudden death, especially on physical
      exertion, and this can constitute the first symptom of the disease. Classified as
      primary or idiopathic for a long time, there have been considerable recent
      advances in the molecular genetics which have allowed the physiopathology of the
      disease to be unveiled. There is great genetic heterogeneity but the different
      genes have in common a coding for sarcomere proteins. Functional studies suggest
      that the mutations entail a primary alteration of sarcomere function, with
      secondary and compensatory hypertrophy. The genetic data equally offer the
      opportunity to re-evaluate the natural history and the clinical spectrum of the
      disease. A better understanding of the disease, coming from these molecular data,
      has allowed a great improvement in the relevance of the information given to
      patients and their relatives during genetic counselling consultations. The
      performance of a genetic test with a medical aim can equally be discussed in
      certain specific situations.

PMID- 14694780
TI  - [Genetics and dilated cardiomyopathy].
AB  - Dilated cardiomyopathy is characterised by dilatation associated with ventricular
      dysfunction and represents the leading cause of cardiac transplantation. The
      aetiology of dilated cardiomyopathy is either multifactorial (about 70% of cases)
      with genetic and environmental components or monogenic (about 30% of cases) by
      autosomal dominant transmission. One of the features of this cardiomyopathy is
      its very wide range of genetic abnormalities and of its phenotype expression. In
      the multifactorial forms, several polymorphisms have been associated with the
      predisposition or with the severity of the phenotype. However, these associations
      have only been observed in a small number of cases and require further
      confirmation. In the monogenic forms, many culprit genes and morbid loci have
      been identified. These genes code essentially the proteins involved in the
      architecture of the cardiomyocyte suggesting mechanisms of action which still
      remain largely hypothetical. To improve the management of patients and their
      relatives, other morbid genes remain to be identified in addition to
      understanding the precise molecular and physiological mechanisms which trigger
      the disease.

PMID- 14694781
TI  - [Genetics and cardiac arrhythmias].
AB  - The identification of the first gene locus of hereditary arrhythmias was made
      over 10 years ago. In the last few years, considerable progress has been made and
      the number of culprit genes for cardiac arrhythmias has rapidly increased. This
      has been the fruit of close collaboration between clinicians, geneticists and
      physiologists. This work has demonstrated the heterogenous nature of genetics of
      diseases. It has led to a better understanding of underlying physiopathological
      mechanisms by the study of the relationship between gene and clinical
      abnormalities. In addition, analysis of phenotypes and genotypes has improved our
      knowledge of the clinical presentation of diseases and opened up new therapeutic
      approaches. These new diagnostic methods have enabled preventive measures to be
      taken to avoid potentially serious arrhythmias. The genetics of cardiac
      arrhythmias is still in its infancy: many culprit genes remain undetected and
      their identification should led to considerable progress in the understanding of
      the physiopathology of arrhythmias and their treatment.

PMID- 14694782
TI  - [Genetic aspects of cardiac conduction defects].
AB  - Degenerative conduction defects are usually considered to be exaggerated ageing
      affecting the conduction pathways. For several years familial forms have been
      described, and a first locus on chromosome 19 and then a first gene, SCN5A on
      chromosome 3 (coding for the sodium channel alpha subunit), have been identified.
      Mutations of this gene can lead not only to congenital conduction defects but
      also to progressive forms of conduction defects similar to Lenegre disease. A
      third locus on chromosome 16 at 16q23-24 has been identified, as have other
      families not linked to the loci described previously. Although it now seems clear
      that conduction defects can have a genetic component, the frequency of the
      familial forms remains to be determined. Important progress could be made in the
      understanding of this disease if other implicated genes were identified. It would
      then become possible to elucidate the different pathophysiological mechanisms
      responsible for conduction defects.

PMID- 14694783
TI  - [Aortic aneurysms excluding Marfan's syndrome].
AB  - The causal factors of aneurysm are not the same in the ascending and abdominal
      aorta. Atheroma is the dominant lesion in the abdominal aorta and genetic
      abnormalities predisposing to "mediacystic necrosis" are more frequently observed
      in ascending aortic aneurysms. The causal genetic abnormalities are multiple:
      abnormalities of fibrillin type I in Marfan's syndrome, collagen abnormalities in
      the Ehlers-Danlos syndrome, abnormalities of microfibrils, possible metallo
      proteases, with many gene candidates. Finally, some ascending aortic aneurysms
      are associated with bicuspid aortic valves, some of which are familial. Familial
      factors are less evident in abdominal aortic aneurysms: genes favoring atheroma
      may be responsible but the factors which predispose to dilatation and non
      stenosis are not well known: they would seem to be general factors because the
      tendency to arterial dilatation is diffuse. In all cases, because of the high
      risk of disease in a close relative, a familial enquiry would seem to be
      justified with echocardiography for close relatives of affected subjects,
      especially when young and female.

PMID- 14694784
TI  - [Marfan syndrome].
AB  - Marfan's syndrome is a monogenetic disease with an autosomal dominant
      transmission generally accompanied by type I fibrillin abnormality. This widely
      distributed molecule participates in the structure of connective tissues so that
      any aberration may result in disease of many systems: skeletal morphology,
      dislocation of the lens, neurological or cutaneous signs and dilatation of the
      aorta predisposing to dissection, mitral valve prolapse being a common
      association. The diagnosis, clinical because of the size of the culprit gene and
      the multiplicity of the possible mutations, is sometimes difficult, and
      diagnostic criteria have been proposed. It is important to make the diagnosis
      because treatment is based on the restriction of violent exercise, betablocker
      therapy and regular echocardiographic monitoring of the ascending aorta, the
      region at highest risk of dilatation and dissection. A family enquiry is
      essential to make the diagnosis before the onset of complications in pauci
      symptomatic patients (great intra-familial variability). Pregnancy poses special
      problems in these patients.

PMID- 14694785
TI  - [Genetics and essential hypertension: candidate genes or screening of the whole
      genome?].
AB  - Essential hypertension is a major cardiovascular risk factor in the
      industrialised countries. Its hereditary nature has been well established in many
      familial studies: about 30% of blood pressure variance is thought to be
      genetically determined. However, the identification of the culprit genes has met
      with many difficulties: the multitude of genes, the effect of which is difficult
      to appreciate, the many possible genetic polymorphisms of each gene studied, the
      very important role of environmental factors (diet, physical activity, etc...) on
      the blood pressure itself or on the effect of the genes which control the blood
      pressure. With the exception of some rare caricatural forms of mendelian
      transmitted hypertension, the search for genes has focused on large case control
      studies and/or studies of siblings with hypertension. Two main approaches are
      used with these collections of subjects. The first consists of analysing so
      called "candidate" genes which code for proteins whose function is known and
      which may influence the blood pressure. In the last ten years, many candidate
      genes have been assessed with often controversial results. The second approach is
      to carry out, with no a priori, a complete screen of the genome. These more
      recent studies have also provided contradictory results. To date, the results
      illustrate the difficulty of genetic analysis of a complex trait and the
      necessity of more integrated approaches: analysis of combination of
      polymorphisms, analysis of a phenotype under standardised environmental
      conditions, analysis of gene-environment interactions.

PMID- 14694786
TI  - [Mendelian arterial diseases. Pseudoxanthoma elasticum, Ehlers-Danlos vascular
      syndrome, Rendu-Osler disease].
AB  - Understanding the features of the various hereditary vascular pathologies allows
      consideration and confirmation of the diagnosis, and a search for treatable
      hidden disorders, avoiding harmful investigations, initiating follow up,
      performing family investigations and providing genetic counselling.
      Pseudoxanthoma elasticum must be considered in the presence of calcified distal
      arteriopathy of the lower limbs in a young subject without any other aetiological
      aspects. Cutaneous or mucosal lesions confirmed on histological examination,
      angioid streaks at the back of the eye and a family history support the
      diagnosis, which is confirmed by showing pathogenic mutations of the ABCC6 gene.
      It is then important to search for a peripheral disorder in other arterial
      territory, a low grade coronaropathy, hypertension and an endocardial disorder.
      Prescription of antithrombotics must be made carefully because of the risk of
      gastro-intestinal haemorrhage. Vascular Ehlers-Danlos syndrome is suspected in a
      subject less than 30 years old with diffuse aneurysmal disease, spontaneous
      arterial rupture or dissection, a carotido-cavernous fistula or early onset
      varices. Demonstrating an ecchymotic tendency or an acrogeric morphology,
      especially in a familial context, warrants cutaneous biopsy for
      anatomopathological examination and fibroblast culture for a study of the C0L3A1
      gene. When the diagnosis is suggested, it is advisable to prohibit any arterial
      puncture, cold surgery or gastro-intestinal endoscopy. The search for aneurysmal
      lesions must be performed by non-invasive imaging. The therapeutic management
      requires specialised teams. The combination of repeated epistaxis, muco-cutaneous
      telangectasia and similar characteristics in a family suggests the diagnosis of
      Osler-Weber-Rendu disease. The search for iron deficiency, gastro-intestinal
      bleeds and pulmonary, hepatic or cerebral arterio-venous malformations is then
      necessary. Besides skilled endovascular management when indicated, it is
      important to advise every patient with a pulmonary arterio-venous malformation to
      take antibiotic prophylaxis against cerebral abscess in situations at risk of
      bacteraemia.

PMID- 14694787
TI  - [Genetics of cerebral vascular accidents].
AB  - Ischaemic or haemorrhagic cerebral vascular accidents (CVA) are the second cause
      of premature death in Western countries. Their pathophysiological mechanisms are
      very heterogeneous and implicate environmental and genetic factors. The recent
      identification of several genes implicated in the rare monogenic forms of CVA,
      such as hereditary cerebral amyloid angiopathy, cerebral cavernous angioma or
      CADASIL, has had immediate diagnostic applications for patients and their
      relatives, and has opened new insights into the mechanisms governing angiogenesis
      and/or vascular homeostasis. In the multifactorial forms of CVA, by far the most
      frequent, the role of a genetic factor is much more moderate, making
      identification of the implicated genes difficult. A very great number of
      association studies have been performed in order to examine the possible
      implication of candidate genes due to their known or supposed functions, but very
      few genetic variants have been associated with an increased risk of CVA, this
      increase being modest moreover. Quite recently an approach combining genetic
      linkage analysis and a haplotypic association study has allowed the localisation
      and identification of a new gene, phosphodiesterase 4D, implicated in ischaemic
      CVA, and the localisation on chromosome 7 of a gene implicated in the occurrence
      of cerebral aneurysms, thus raising new hopes in these multifactorial form.

PMID- 14694788
TI  - [Genetics of venous thromboembolism].
AB  - Venous thrombo-embolic disease is a multifactorial disease which arises in
      situations of thrombosis risk with poorly understood genetic and/or acquired risk
      factors. Constitutional anomalies concerning five coagulation proteins
      (antithrombin, protein C, protein S, factor V and prothrombin) are established
      risk factors for which the harmful role has been demonstrated in thrombophilic
      families and/or in case-control studies. New studies (twin studies, GAIT study)
      which use joint subjects and appropriate statistical methods are aimed at a
      better understanding of the genetic component and the environmental component of
      thrombotic risk. They have allowed demonstration of the importance of the
      contribution of heredity to the variability of the coagulation parameter
      concentration and the variability of susceptibility to thrombosis, and have
      implied the influence of genes with pleiotrophic effect. The identification of
      these new loci will allow a better evaluation of the components of thrombotic
      risk and perhaps lead to individualised preventive therapeutic management.

PMID- 14694789
TI  - [Genetics and dyslipidemias].
AB  - The intense search which has developed around understanding the pathological
      mechanisms of atherosclerosis has underlined the complexity of a process which
      involves very many proteins, the products of genetic information. This
      observation, combined with genetic epidemiological data, has introduced the
      notion of familial susceptibility applicable to atherogenic dyslipidaemia. This
      susceptibility relies on the presence of mutations, more or less frequent in the
      population, affecting the key genes in plasmatic lipid transport. The mutations
      which are currently the best documented concern the genes involved in the
      metabolism of atherogenic lipoproteins: LDL-receptor, apo B or apo E.
      Nevertheless, a better understanding of the inverse transport of cholesterol
      would allow progressive demonstration of the mutations affecting HDL metabolism.
      The aim of such work encompasses the characterisation of the most relevant
      mutations for defining coronary risk, and a better understanding of the
      interactions of these mutations with conventional environmental risk factors.

PMID- 14694790
TI  - [Genetic aspects of the athlete's heart].
AB  - Positive myocardial and vascular adaptations can be observed in case of a high
      physical training practice. These clinical, electrocardiographic and
      echocardiographic patterns constitute the so called "athlete's heart". These
      adaptations are linked to hemodynamic and neuro-hormonal factors but also for a
      large part to genetic factors. The "athlete's heart" genetics aspects are many.
      These genetic factors play a role not only for the absolute physical performance
      but also for the cardio-vascular responses to physical training. In other words,
      it is possible to separate the "high-responders" and the "low-responders" to
      physical training. A high number of genes seem involved in physical performance
      and in cardiovascular responses. Among them the renin-angiotensin system genes
      have been presently the most studied, because of their link with cardiac
      hypertrophy. The impact of the genes involved in the autonomic nervous system
      regulation begins also to be explored. In the future, several other genetic ways
      would be studied to really understand all the genetic aspects of the "athlete's
      heart".

PMID- 14694791
TI  - [The genetics of multifactorial cardiovascular disease. How significant for the
      cardiologist?].
AB  - Cardiovascular disease represents the prime cause of mortality and morbidity in
      many countries. The occurrence is affected by pre-existing risk factors of which
      the best known at the moment are the environmental risk factors. However, for the
      same level of environmental risk, two individuals do not necessarily have the
      same probabilities of developing a cardiovascular event. In effect, the
      constitutional component, accounted for by details in everyone's genetic makeup,
      can significantly alter this risk. The characterisation and identification of the
      mutations responsible for this variation in individual susceptibility are complex
      in the case of multifactorial diseases such as cardiovascular disease. Several
      studies now allow a glimpse at the expected benefits of understanding this
      genetic component, as far as diagnosis, prognosis and pharmacogenetics are
      concerned. The current explosion in high capacity genome techniques will herald
      new therapeutic approaches likely to further improve the survival and quality of
      life for our patients.

PMID- 14694793
TI  - [Customer focus as an issue for the insurance industry].

PMID- 14694792
TI  - [Genetic counseling in cardiology].
AB  - Progress in the recognition of genetic factors implicated in cardiovascular
      diseases is now such that it poses the question of how to integrate these data
      into a clinical perspective. To be able to give the most relevant information to
      the patient and his family, and to use this information to optimise the medical
      management have become new objectives. This can only be achieved with the close
      collaboration between cardiologist and the genticist, who knows the legislative
      framework which governs the performance of genetic tests. During the genetic
      counselling consultation, and after time for compiling information on the disease
      and the family, the geneticist gives the most suitable information on the genetic
      nature of the disease. Depending on the illness, cardiological investigation for
      the relatives could be advocated. The performance of a molecular test is then
      discussed, as a function of its feasibility, relevance and the wishes of the
      patient. The complexity of the medical and psychological stakes varies according
      to the situation (presymptomatic diagnosis, prenatal diagnosis, diagnostic test,
      prognostic test) and the condition. In all cases, strict rules perfectly laid
      down by legislation must be respected, in such a way as to protect the patient
      from possible unfavourable repercussions and to assure him of better medical
      management and a greater well-being.

PMID- 14694794
TI  - [Development and current status of non-specific enzyme therapy].
AB  - Non-specific enzyme therapy does not intend the catalysis of definite steps of
      metabolism, but claims to stimulate regenerative processes in general. Initially,
      non-specific enzyme therapy had been considered to be a promising approach. The
      growing knowledge in basic research and the lack of evidence for clinical
      effectiveness rendered the predominantly oral application of enzyme preparations
      for non-specific treatment outdated by the 1960s. In Germany, however, the
      absence of strict legal regulations prevented the deregistration of drugs
      designed for non-specific enzyme therapy. Furthermore, numerous clinical studies
      were initiated by the leading producer of enzyme preparations in Germany in order
      to provide the scientific confirmation missing so far. Our critical and systemic
      review of the published trials shows that neither the mechanism of action could
      be enlightened, nor the clinical benefit of non-specific enzyme therapy proven on
      an acceptable level of scientific standards.

PMID- 14694795
TI  - [Validity of smoking histories].
AB  - Validity of smoking histories was investigated retrospectively in 185 cases of
      lung cancer, which are compensated as occupational diseases. We used the files
      inquiry of the occupational disease declarative statement, primary physicians
      information, information from the post-exposure medical surveillance
      examinations, and the files of the former company physicians as data sources.
      From these, the smoking status was determined and compared with single data
      sources. Self-reported information during post-exposure medical surveillance
      examinations tallied well (deviation: 6.5%), whilst physicians' information was
      lacking in 34.6% in (former) smokers. We propose improved sensitisation of
      physicians to the problem of nicotine dependence.

PMID- 14694796
TI  - [On the tasks of the medical director in private German health insurance
      companies].
AB  - The tasks of the medical director in private German health insurance companies is
      largely unknown to the public and to physicians, and there is a lack of
      scientific literature about this subject, though medical directors have a long
      tradition in the German insurance system. The result of a representative sample
      of 826 enquiries to the medical director showed that most of the questions are
      about the medical necessity of medicines, duration of in-patient hospital
      treatment, alternative medicine, extensive laboratory diagnostics, physical
      therapy, the German fee system (GOA) and in recent time also about the
      demarcation of cosmetic surgery from medically necessary surgery, and about anti
      aging therapy and artificial fertilisation. Risk management and consulting about
      case and disease management is also increasingly important.

PMID- 14694797
TI  - [Geriatric research and spirituality].

PMID- 14694798
TI  - [Unequal chances for reaching 'a good old age'. Socio-economic health differences
      among older adults from a life course perspective].
AB  - This article provides an overview of the socioeconomic inequality in physical and
      psychological health of older adults between 55 and 85 years of age, with a focus
      on the older adults whose socioeconomic status (SES) remains at a low level all
      their life. Data are derived from 1471 men and 1568 women, participating in the
      Longitudinal Aging Study Amsterdam (LASA) in 1992/1993. Based on the parental and
      own level of education, respondents are divided in four categories: those with a
      life time low level of SES, those with downward or upward mobility in SES, and
      those with a life time high level of SES. Logistic regression analyses showed
      that older adults with upward SES mobility and life time high SES, had a lower
      risk for functional limitations, chronic diseases (men only), 6-year mortality,
      depression and loneliness, compared with the older adults with life time low SES.
      The disadvantaged position of the low SES persons with regard to age, health and
      psychosocial conditions explained the SES differences in depression, but SES
      differences in mortality (for men) and in functional disability (for men and
      women) are not explained by the risk factors under study. SES differences in
      loneliness were attributed to differences in psychosocial conditions. Lifestyle
      did not add to the explanation of any of the SES differences. There were only
      small differences between those with a life time low SES and those with downward
      mobility in SES. It is concluded that a low level of education (regardless of the
      parental level) contributes to restricted psychosocial conditions, health
      problems and low well-being in old age, thereby decreasing the chances for a
      'good old age' considerably.

PMID- 14694799
TI  - [Personality diagnosis in elderly psychiatric patients using a Delphi technique].
AB  - A Delphi-technique was used as part of the development of a screening instrument
      to diagnose personality disorders in the elderly. Several statements regarding
      this subject were tested. Fifty-three Delphi-members, with expertise in the field
      of mental health services for the elderly and knowledge about the concept
      'personality disorder', gave their opinion on the statements. In three successive
      rounds we aimed to get consensus as well as agreement on the contents of the
      statements. In the first round the Delphi-panel confirmed the importance of
      diagnosing personality disorders, with regard to individual therapy in older
      adults and psycho-educational activities. The DSM-IV Axis II criteria and related
      assessment-instruments do not take into account the emotional and social context
      of the elderly people. In the second round the Delphi-panel endorsed the
      importance of several information sources namely biographical information,
      informant information, behavioural observations and the reactions of the
      therapist himself. In the third round, 44 items considering diagnostics on
      personality were pro-pounded to the panel. There was agreement as well as
      consensus on 25 out of the 44 items. In conclusion, adjusting the DSM-IV Axis II
      criteria to the elderly will improve the quality of the diagnostics. Developments
      of a specific screening instrument for older adults probably will also increase
      the quality of the diagnostics.

PMID- 14694800
TI  - [Anxiety disorders in nursing homes: a literature review of prevalence, course
      and risk indicators].
AB  - Psychiatric disorders such as dementia and depression are highly prevalent in
      nursing homes. The prevalence of anxiety disorders is less clear. Prevalence,
      course and risk-indicators of anxiety disorders among nursing home residents were
      examined, based on a review of the literature. Medline and PsychINFO searches
      were conducted for 1966-2002. Twelve studies were considered relevant. These
      differed substantially with respect to study-population, diagnostic instruments
      and diagnostic criteria that were used and the specific anxiety disorders
      investigated. The prevalence of anxiety disorders ranged from 0-20%. Only in one
      study the course of anxiety disorders was investigated. About 60% of the nursing
      home residents recovered in one year. The most important risk-indicators for
      anxiety disorders identified were: female sex, depression, lack of social
      support, poor physical health and functional and cognitive impairments.
      Generalization of these results to the Dutch nursing home population is
      restricted by the substantial heterogeneity of the studies. Further studies are
      required to provide reliable estimates of prevalence, course and risk-indicators
      of anxiety disorders among nursing home residents using appropriate diagnostic
      instruments and adjusted diagnostic criteria. This will enhance detection and
      improve treatment of anxiety disorders among nursing home residents.

PMID- 14694801
TI  - [Confusing stories, not always confusion! Language disorders and dementia].
AB  - Sometimes confusing stories may have unexpected causes. A confused patient is not
      necessarily delirious or demented. We present three patients in which diagnosis
      was difficult. Their confusion appeared to be caused only partially by memory
      impairment. Dementia often presents with memory impairment, but sometimes a
      language disorder is more prominent. Ten percent of the dementias show language
      disturbances as the first sign. Language disturbances may exist for a long time,
      even before the onset of the memory impairment. The language disorder causes
      difficulty in proper judgment of memory. Logopedic examination is necessary to
      diagnose the language disorder. Neuropsychological testing should take the
      language disorder into account. Diagnostic accuracy is important. Distinguishing
      dementia from a language disorder has implications for the judgment of the
      patient's (dis)abilities and management.

PMID- 14694802
TI  - Testing your diagnostic skills. Case no.1. Verruciform xanthoma.

PMID- 14694803
TI  - Family, community, tradition drive dentist of the year.

PMID- 14694804
TI  - [Food and nutritional security in a risk area for malaria].
AB  - To explore some relationships between alimentary and nutritional security (SAN)
      and nutritional status in an endemic malaria community, applying qualitative and
      quantitative methods simultaneously. The study was descriptive and prospective.
      The population were all farming Afro-American families who live in the basin of
      the river Valle (Bahia Solano. Choco, Colombia) that derived the base of their
      feeding of the agriculture. The SAN was measured from the monthly availability of
      foods and was classified in adequate and inadequate according to the available
      monthly caloric balance percentage. We determined the risk of acute malnutrition
      (indicative P/T), chronic (T/E), global (P/E) and risk of thinness (BMI). We
      sought for malarian cases. The official data of illness were revised. We applied
      surveys to know the morbidity and knowledge, attitudes and practices in malaria
      infections, 29% of homes had alimentary insecurity. There was protein deficit and
      iron of high availability, calcium and vitamin A in 100% of families. In children
      under 6 years old, we found 31% and 69%, in same order, with low P/T and T/E,
      while in the 6-10 year old children had 14% and 41%, respectively. In adolescents
      (11 to 17 years old) the risk of thinness was 15% and in adults 3%. There was not
      association between alimentary available and family nutritional status. These
      results suggest subclinics deficiencies of micronutrients.

PMID- 14694805
TI  - Interactions among indicators of B1, B2, B6 and vitamin C status in university
      students.
AB  - In 209 young university students (109 males and 80 females) with body mass index
      within the normal range, the activation coefficient of the erythrocyte
      transketolase (ETKAC) glutathione reductase (EGRAC) and aspartate amino
      transferase (EASTAC) as well as the circulating levels of vitamin C were
      determined. Using the usual cutoff points for ETKAC and serum vitamin C and
      higher than usual cutoff points for EASTAC and EGRAC 99, 95, 92, and 87% of the
      study subjects exhibited activation coefficients which were compatible with an
      acceptable status for vitamin B2, B6, C and B1 respectively. A correlation
      analysis showed a high correlation (r = 0.81) between erythrocyte indicators of
      B1 and B2 status a lower correlation between indicators of the status of these
      vitamins and B6 and no correlation between the indicators of B1, B2, and B6
      status and serum vitamin C. This study indicated that in this largely
      nutritionally adequate population, the activation coefficient of the erythrocyte
      enzymes used here as markers of the nutritional status of B1, B2, and B6 were
      related between themselves and varied in the same direction. These changes,
      however, were not associated with circulating levels of vitamin C.

PMID- 14694806
TI  - [Dietetic determinants on food intake and effects in body weight regulation].
AB  - Obesity is a multifactorial pathology currently considered one of the main public
      health problems. Its prevalence is increasing dramatically in the last decades,
      reaching huge rates in Brazil and many other countries. Regardless of the factors
      associated with genetic predisposition, this pathology is often associated with
      abnormal food intake, and also with high consumption of caloric foods and
      sedentary habits. Thus, obesity is the result of an imbalance between food intake
      and energy expenditure. One of the greatest research interests in nutrition has
      currently been the dietetic determinants that may exert an influence on the
      process of food intake, as well as the role of foods on physiological, physical
      and chemical factors most related to the processes of satiation and satiety.
      Based on these aspects, this paper analyzes several research works to gain a
      better insight of the dietetic factors affecting food intake and body weight
      regulation.

PMID- 14694807
TI  - [Selection of the more adequate prediction index to estimate the frame size a
      group of institutionalized and free living elderly in Venezuela. (Preliminary
      study)].
AB  - The objective of the study was to identify an easy to measure indicator of body
      frame size to allow refinement of anthropometric nutritional evaluation. Body
      dimensions and frame indices related to height, which might be potential frame
      size predictors in the elderly, were studied. In 307 subjects (163 women, 144
      men) aged 60-99 years of whom 187 were institutionalized and 120 free-living
      outpatients, weight, height, mid-arm circumference; triceps, subscapular,
      midthigh and calf skinfolds; elbow, wrist, femur and biacromial widths, were
      measured. Body mass index, upper arm muscle area, upper arm fat area, fat
      percentage, sum of skinfolds and frame indices were calculated. Results were
      calculated in function of age, sex and life-style. Biacromial breadth,
      biacromial/height index, wrist breadth and wrist/height index gave variable
      correlations with indices of body mass and body fat. Femur breadth and
      femur/height index were significantly correlated with body fat indices. Elbow
      breadth, humerus/height index were not correlated to body fat indices, but were
      significantly correlated with weight, height and fat free mass. Elbow breadth and
      humerus/height index fulfilled most of the criteria of good predictors of body
      frame size in the group pf elderly studied.

PMID- 14694808
TI  - [Nutritional recovery of mild and moderately malnourished children under two
      different treatment approaches (ambulatory versus day-care)].
AB  - This retrospective analysis was conducted between May 1997 and May 2000 at the
      Centro de Atencion Nutricional Infantil de Antimano, CANIA, in Caracas, Venezuela
      to assess the efficacy of two treatments (ambulatory versus day-care) of mild and
      moderate malnourished children. Inclusion criteria were: children under 10 years
      old with mild and moderate malnourishment, who attended a minimum of 3 control
      visits during a period of 12 months. One hundred fourteen malnourished children
      were included: fifty seven in ambulatory treatment and fifty seven in day-care
      treatment paired per nutritional diagnosis, gender and age (thirty nine mild and
      eighteen moderate malnourished children). The nutritional recovery criterion was
      weight for height above tenth percentile. No relation was found between treatment
      approaches and nutritional recovery at 3 and 6 months of treatment. In the group
      of mild malnourished children, the percentage of recovered patients at 3 months
      of treatment, that kept their recovered condition at 6 months was 83% (15/18) in
      the ambulatory treatment and 82% (18/22) in the day-care treatment Age of
      children, associated disease, acute morbidity, dietetic risk and mother's
      education and age were not associated with nutritional recovery at 6 months of
      treatment (p > 0.05). The day-care approach resulted as effective as ambulatory
      in mild malnourished children. In moderate malnourished new studies will need to
      be conducted with greater number of patients.

PMID- 14694809
TI  - [Vitamin A deficiency among preschool children: a re-emerging problem in Costa
      Rica?].
AB  - Based on the 1996 National Nutrition Survey, this study shows the prevalence of
      Vitamin A deficiency (VAD) among 567 Costa Rican urban and rural 12-83 months old
      children. In overall, the prevalence of VAD (plasma retinol < or = 20
      micrograms/dl) was 8.8%. No difference was found even when data were analyzed by
      area and gender. Around 30% of preschool children were at risk of VAD (plasma
      retinol between 20.1-30 micrograms/dl). The proportion of children at risk for
      retinol deficiency was significantly higher in rural area in comparison with
      urban area (38.9% and 28.0% respectively, p < 0.05). Lineal regression analysis
      showed that plasma retinol levels were negatively related to the number of family
      members and positively related to mother's schooling. Our results suggest a
      possible impairment in vitamin A status of preschool children.

PMID- 14694810
TI  - [Effect of cooper supplementation on blood pressure values in patients with
      stable moderate hypertension].
AB  - Copper (Cu) deficiency is associated with changes in arterial pressure. The
      effect depends of the age of initiation of the copper-deficient diet. Copper
      deficiency started at a young age causes hypotension. When initiated in older or
      adult animals, copper deficiency can cause hypertension. A case-control study was
      carried out to investigate the effect of administrating 5 mg Cu/d in 60 subjects,
      both genders, with mild stable hypertension, pharmacologically untreated (treated
      group) and compared with 60 hypertensives (control group) who were matched by
      gender, age, body weight, smoking habits, calories, fat and salt intake (NaCl),
      and physical activity. Hypertension was diagnosed when the blood pressure was >
      150/95 mm Hg. Mean age, mean corporal weight and risk factors were similar in
      both groups. The results suggested the existence of a marginal deficiency of the
      trace element in 62% of subjects and demonstrated that Cu decreases systolic (r =
      -0.963) and diastolic (r = -0.981) blood pressures in treated group (p < 0.05).
      Control patients did not show significant changes in their arterial pressures.
      These findings indicate a functional alteration in human blood pressure
      regulation during mild copper depletion and suggest that Cu could be used in the
      treatment of stable moderate arterial hypertension. Further investigation is
      needed to determine the extent of this influence.

PMID- 14694811
TI  - Microbiological contamination of enteral feeding solutions used in Costa Rican
      hospitals.
AB  - Enteral feeding is the most common and preferred modality for providing
      nutritional support to hospital patients with a functional gastrointestinal tract
      that can not satisfy their nutritional requirements. Nevertheless, enteral
      feeding may be an important cause of bacterial infection. The aim of this study
      was to evaluate the microbial contamination level of enteral feedings distributed
      in Costa Rican hospitals. A total of 124 samples of enteral feeding, coming from
      five different hospitals from San Jose, Costa Rica, were evaluated during the
      second semester of 1997 and first of 1998 for the presence and identification of
      total and fecal coliforms, Pseudomonas sp. and Listeria sp. A subpopulation of
      the Pseudomonas isolated was analyzed for their antibiotic susceptibility
      patterns. The concentration of Gram negative rods in the samples of enteral
      feeding solutions ranged from 10(3) to 10(7) CFU/mL, markedly exceeding the
      permissible level (10(2) CFU/mL or less). The coliforms most frequently isolated
      included Enterobacter cloacae, Escherichia coil, Serratia sp. and Klebsiella
      pneumoniae. Pseudomonas sp. was isolated in more than 70% of the samples made
      from commercial based solutions, fruits and vegetables. P. aeruginosa and P.
      fluorescens were the species most frequently isolated. Listeria sp. was not
      isolated from enteral solutions samples. The results obtained demonstrate that it
      is urgent to assure strict hygiene during the preparation and handling of all
      enteral feed in order to avoid bacterial growth. The implementation of HACCP
      (Hazard Analysis and Critical Control Points) system will be required in a near
      future for better quality control of enteral nutrition mixtures.

PMID- 14694812
TI  - [Microbiological and physicochemical evaluation of pasteurized nectar elaborated
      with tree tomato (Cyphomandra betaceae Sendth)pulp].
AB  - Tree tomato (Cyphomandra betaceae Sendth) is a species from high tropical
      regions. In Venezuela, it is cultivate at the Andean and Aragua state but its
      consumption is restricted as fruit-fresh, though it a nutritious and industrial
      potential due its provitamin A content. In this research four nectars were
      elaborated in proportion I L pulp/4 L of water (1:4) and addition of ascorbic
      acid (I: 0%; II: 0.5%; III: 1.0 y IV: 1.5%). The nectars were pasteurized (60
      degrees C for 30 min), tuned into amber bottle, and stored under refrigeration
      conditions (7.0 +/- 1.0 degrees C). Weekly during 21 days the mesophilic
      bacteria, molds, yeasts, total coliforms (MPN/mL), pH, degree Brix, acidity,
      total carotenoids, vitamin C and total sugars were evaluated. The mesophilic
      bacteria content was < 200 UFC/mL for every formulation on the first day the
      evaluation, molds and yeasts were < 10 UFC/mL and the total coliforms (NPN/mL) <
      3 until the third evaluation. No significant differences (P > 0.05) were founded
      on: pH. degree Brix and total sugars. Significant differences (P < 0.05) were
      founded in vitamin C and total carotenoids content. Sensorial analysis did not
      show significant differences between formulations for the smell and flavor
      attributes, when the color was discriminate during the evaluations. The
      formulation I (without acid ascorbic) had more preference due its color. In
      conclusion, the nectars showed useful life of 14-21 days under refrigeration
      condition storage due to the adequate physicochemical and microbiological quality
      of the product.

PMID- 14694813
TI  - [Efficacy and stability of ammoniation process as aflatoxin B1 decontamination
      technology in rice].
AB  - Rice, a cereal widely used in Venezuela for human and animal nutrition, is
      susceptible to aflatoxin contamination in the field and during storage.
      Therefore, the goal of this research was the evaluation of the efficacy and
      permanence of the ammoniation process through high pressure/high temperature
      (HP/HT) and atmospheric pressure/moderate temperature (AP/MT) conditions applied
      to rice samples artificially contaminated with aflatoxin B1. For this purpose a
      2k design was drawn up considering the temperature, the rice moisture and the
      process time as variables. Under both sets of conditions, aflatoxin B1
      concentration was reduced in a range of 90% to 100%. After in vitro stomach
      digestion simulation, toxin reversion ranged from 0% to 19%. In conclusion, the
      process efficacy and permanence were achieved through the use of high temperature
      and long process time for both sets of conditions (HP/HT and AP/MT),
      respectively.

PMID- 14694814
TI  - [Effect of extrusion on the activity of anti-nutritional factors and in vitro
      digestibility of protein and starch in flours of Canavalia ensiformis].
AB  - The effect of the extrusion (155 degrees C, 20% moisture, screw speed 75 rpm,
      feed speed 205 g min-1) on antinutritional factors of Canavalia ensiformis was
      studied. In vitro protein and starch digestibilities were assessed. The extrusion
      not affect protein content (23%) in the flours, but significantly (P < 0.01)
      decrease moisture content. The protein digestibility values were improved from
      57.5 to 89.5%, these values were lower than casein (98.19%). The digestibility of
      starch values were improved from 37.7 to 53%. The protease inhibitors activities
      (trypsin and chymotrypsin) and alpha-amylase inhibitor activity were reduced by
      95%. The haemagglutinating activity was eliminated as result of the high
      temperature employed during the extrusion process. The canavanine content in the
      flours were not affect by the treatment of extrusion.

PMID- 14694815
TI  - [Maturation study of low fat Chanco cheese made with homogenized milk].
AB  - The purpose of this study was to evaluate the influence the use of homogenization
      of different proportions of milk--which allow to increase the yield in the
      process and probably to improve sensorial characteristics of the cheese--has on
      the ripening of low fat Chanco cheese. Five treatments (three replicates each)
      were studied, two corresponded to control (normal fat and low fat) and the other
      three treatments were low fat using partially homogenized milk in the following
      percentages of the total volume of milk; 12.5, 25 and 50%. Standard methodology
      was used to monitor the evolution of ripening in terms of moisture, fat and total
      protein content, ripening index (NS/NT%), lipolysis (ADV), pH, sensorial quality
      and micro structure of the product. The low fat treatments with homogenized milk
      showed less fat losses in the whey and consequently increased yields. This study
      allowed us to know the low fat Chanco cheese maturation profile, low fat
      treatments with homogenisation showed a higher degree of lipolysis than the non-
      homogenized low-fat control although it was lower than normal fat control. No
      differences in terms of the development of proteolysis were observed. The low-
      fat homogenized treatments did not show improvement in the flavor neither in the
      cheese firmness probably due to the short ripening period (21 days) of this
      cheese variety, nevertheless T3 presented some advantages which could be improved
      applying simultaneously another technological helps.

PMID- 14694816
TI  - [Chemical composition and seasonal fluctuations of the edible green seaweed,
      Monostroma undulatum, Wittrock, from the Southern Argentina coast].
AB  - The chemical composition of green seaweed, Monostroma undulatum, Wittrock,
      growing in the Southern Argentina coast, was studied. Samples were collected in
      Puerto Deseado, province of Santa Cruz (47 degrees 45'L.S., 65 degrees 55'L.W.),
      from October to December 1999 and 2000. It has been analyzed six sample during
      this period. Algae were washed with sea water and dried at room temperature for
      24 hs. Moisture, nitrogen, lipids and ashes were determined according to AOAC;
      fiber (total, soluble and insoluble), according to Lahaye. After mineralization
      with nitric acid, sodium and potassium were determined by flame photometry,
      calcium by complexometric method, and phosphorus by Gomori's method. The ranges
      expressed per 100 g dry algae were: protein (Nx6.25): 12.89-21.85; ashes (g):
      33.92-40.05; lipid (g): 0.32-1.47; total fiber (g): 14.36-19.6; digestible
      carbohydrates (calculated by difference) (g): 20.86-32.48; sodium (g): 7.39
      13.11; potassium (g): 1.38-3.18; calcium (mg): 149-226; phosphorus (mg): 190-447;
      Vitamin C (mg): 159-455. These results show that this green seaweed is an
      important source for protein, fiber, macronutrients minerals and vitamin C,
      during the macroscopic period. There was an important fluctuation that must be
      taken into account to consider the commercial collection to use it in human
      nutrition.

PMID- 14694817
TI  - New data on the total lipid, cholesterol and fatty acid composition of raw and
      grilled beef longissimus dorsi.
AB  - Simultaneous analyses of total lipids, cholesterol and fatty acids were carried
      out on raw and grilled beef longissimus dorsi trimmed of external fat.
      Cholesterol was determined by high performance liquid chromatography and the
      fatty acids by gas chromatography. Mean total lipid (g/100 g) ranged from 2.1 to
      2.6 for raw beef and 3.5 to 4.0 for grilled beef steaks. Cholesterol levels
      (mg/100 g) ranged from 40 to 43 for raw beef and 67 to 70 for grilled beef
      steaks. The main intramuscular fatty acids of the raw and grilled meat were 14:0,
      16:0, 16:1n7, 18:0, 18:1n9, 18:1n7 and 18:2n6. Grilled lean beef steaks had
      significantly higher contents of the principal fatty acids and most of the minor
      fatty acids. The higher values for the three components in the grilled meat were
      due to loss of moisture during grilling. There was no significant difference
      between the apparent and true retentions values, both indicating no significant
      loss or degradation of total lipids, cholesterol and fatty acids during grilling.

PMID- 14694818
TI  - [Mineral nutrient content in cow milk and dairy products in Argentina].
AB  - Cow milk and dairy products supply essential inorganic elements for humans, and
      constitute the most important source of bioavailable calcium in our diet. In
      order to obtain data about mineral nutrient composition of dairy products that
      are produced and sold in Argentina, the contents of Ca, P, Mg, Na, K, Fe, Zn and
      Cu in whole and low fat fluid milk, dried milk and yogurt were analyzed. P was
      assessed by a colorimetric method, and the other elements by atomic absorption
      spectroscopy. In raw milk, the mineral content shows a certain degree of
      variability, in addition to the variability introduced by the different
      processing conditions, in order to meet the requirements prescribed by trade
      regulations and to produce dairy products. In all cases, skimming increases the
      concentration of mineral nutrients, which is especially remarkable in Ca
      contained in skimmed milk powder. In yogurt, added milk solids like dried milk or
      evaporated milk appreciably increase the mineral content, even more so if
      ultrafiltrates are used. These ultrafiltrates increase the Ca/P ratio, which
      probably improves Ca bioavailability. The results obtained in these analyses
      provide data that are not yet available from the National Table of Food
      Composition, and which prove necessary and fundamental for nutritional and
      dietary evaluation.

PMID- 14694819
TI  - Comparative mortality of persons with mental retardation in California 1980-1999.

PMID- 14694820
TI  - Are young individuals with acute myocardial infarction insurable? The discrepancy
      between clinical observed mortality and comparative mortality.

PMID- 14694821
TI  - Relationships between serum lipids and subsequent mortality in an insured
      population.
AB  - OBJECTIVES: To investigate relationships between serum lipids and all-cause
      mortality in an insured population issued policies at standard rates using
      contemporary analytic techniques. BACKGROUND: As with other preferred risk
      factors, differences in lipid profiles can be an important contributor to
      morbidity and mortality endpoints in the general and insured population. To
      better understand the independent contribution of different lipid profiles to
      mortality, contemporary researchers commonly employ multivariate statistical
      techniques. Studies on insured populations utilizing multivariate statistical
      procedures are not commonly published and are employed in this study of an
      insured cohort. METHODS: We studied internal data on direct and reinsurance
      business issued at standard rates, or rated only for abnormal lipids, between
      1975 and 2000 followed through anniversaries in 2001, or prior termination, with
      an average duration of 6 years per policy. Cox proportional hazards models were
      used to study the multivariate relationship between various lipid values
      (cholesterol, cholesterol/HDL ratio, triglycerides) and mortality. RESULTS: Five
      hundred twenty deaths were observed during follow-up. Mortality was noted to vary
      by differing levels of all 3 of the predictor variables of interest. The
      relationship between an abnormal lipid profile and mortality was strongest in
      males and nonsmokers. CONCLUSIONS: In this insured cohort, changes in lipid
      profiles are associated with significant differentials in mortality.

PMID- 14694822
TI  - Risk factors for ill health insurance claims.
AB  - OBJECTIVES: This study examined the information available at application for
      income protection insurance, to determine if any factors were predictive of a
      claim. The strength and significance of such factors were assessed and a
      predictive model was developed. BACKGROUND: The factors underlying life assurance
      risks are well known, but this is not the case for income protection insurance.
      For accurate underwriting of income protection insurance, it is important to know
      what information available at application has power to predict a claim. Improving
      the scientific accuracy of underwriting is good business practice, as well as
      answering the demands of disability legislation. METHODS: We studied all data
      available at application for 959 current claimants and 1417 non-claimants, using
      a case-control study design. Information included applicants' description of
      their occupation, marital status, build and habits, plus a questionnaire asking
      about their personal health. For some applicants medical reports were available
      as well. Information was transcribed onto a database, and univariate and
      multivariate analyses were performed. A predictive scoring system was established
      and its performance measured by receiver operating characteristic curves.
      RESULTS: Significant associations with claiming were found for many variables,
      including age (odds-ratio 1.04, p < 0.001), height (0.11, p = 0.03), smoking
      (2.10, p < 0.001), abstinence from alcohol (1.56, p = 0.01), recent medical
      advice (1.34, p = 0.06), and having had a lower gastrointestinal disorder (1.51,
      p = 0.04). Using all the information from the application, a predictive model was
      constructed. This model had good predictive power with an area under the receiver
      operating characteristic curve of 72%. CONCLUSIONS: Classical underwriting
      factors were generally shown to have predictive power for income protection
      insurance. The predictive scoring strengthens the scientific basis for
      underwriting and could be developed to simplify and expedite the underwriting
      process.

PMID- 14694823
TI  - Liver function tests: what is the risk?
AB  - Five laboratory assays are commonly called liver function tests (LFTs), although
      these tests are neither specific to the liver nor true measures of liver
      function. As a result, alanine aminotransferase (ALT or SGPT), aspartate
      aminotransferase (AST or SGOT), gamma-glutamyltransferase (GGT), alkaline
      phosphatase (ALP) and bilirubin have proven problematic for clinicians and risk
      selection professionals alike. Further, underwriters and insurance medical
      directors find these tests difficult to assess because of the lack of data
      directly relating LFT elevations to mortality outcome. Nonetheless, the tests are
      frequently encountered, so a strategy for evaluating abnormal results is critical
      to ensure accurate and fair pricing. This paper reviews basic information on
      LFTs, available mortality data and the application of this knowledge to the
      underwriting process.

PMID- 14694824
TI  - Sleep apnea: a review for life insurance medical directors and underwriters.
AB  - OBJECT: Obstructive sleep apnea (OSA) is a commonly encountered impairment in
      both clinical and insurance medicine. Surprisingly, relatively few data exist
      regarding the mortality or morbidity of sleep apnea. This paper reviews the
      mortality and morbidity implications of this disorder. METHODS: Literature review
      using Medline. RESULTS AND CONCLUSIONS: Much of the morbidity and mortality
      attributed to obstructive sleep apnea may be due, in part, to the presence of co
      morbid conditions (obesity, hypertension, cardiovascular and cerebrovascular
      disease). An assessment of additional risk attributable specifically to OSA
      requires review of polysomnographic results, including the respiratory
      disturbance index (RDI), minimum arterial oxygen desaturation, minimum and
      maximum heart rates, and sleep architecture. Integral to this risk assessment is
      also the presence and severity of the consequences of OSA, chiefly the severity
      of disability due to daytime hypersomnolence as well as the other co-morbidities
      (control of hypertension, weight gain or loss). It is this author's opinion that
      adequately treated OSA may carry little, if any, mortality risk.

PMID- 14694825
TI  - Attention deficit hyperactivity disorder (ADHD)--life insurance implications.
AB  - Attention deficit hyperactivity disorder (ADHD) is the most common
      neurobehavioral disorder in youth. About one-half of these youngsters continue to
      have symptoms as they enter their 20s. Of these, some also have co-morbid
      conditions such as conduct disorders, psychiatric problems and substance abuse.
      The medical director must be able to recognize the small subset of affected
      individuals whose mortality due to ADHD is greater than that of the standard
      population.

PMID- 14694826
TI  - Hepatocellular carcinoma and hepatitis B e antigen.
AB  - Hepatitis B e antigen serum persistence in an individual chronically infected
      with the Hepatitis B virus may be associated with a greatly increased risk of
      developing cirrhosis and hepatocellular carcinoma. This article presents an
      overview of the Hepatitis B e antigen and discusses the findings of a recent
      study evaluating its associated risk of hepatocellular carcinoma. A gross
      photographic image of hepatocellular carcinoma is provided.

PMID- 14694827
TI  - Obesity and the risk of heart failure.
AB  - An article is reviewed which demonstrates that obesity is associated with an
      increase in the relative risk of heart failure ranging from 1.8 to 5.6 depending
      on the degree of obesity and gender, even when other known risk factors for heart
      failure are excluded. The most reasonable conclusion is that there are one or
      more mechanisms where obesity results in heart failure that have not yet been
      recognized.

PMID- 14694828
TI  - A cineradiographic study of deglutitive tongue movement in patients with anterior
      open bite.
AB  - The purpose of this study was to use cineradiographic images to investigate
      tongue movement during deglutition in anterior open bite patients with tongue
      thrust. Each subject had semi-spherical lead markers attached to the tip and
      dorsal surface of the tongue and was asked to swallow 5 ml of diluted liquid
      barium. Tongue movement during deglutition was recorded in the mid-sagittal plane
      with an X-ray VTR system. The deglutition process was divided into 6 stages to
      analyze the movements of the tip and dorsal surface of the tongue in each stage.
      In open bite patients, both the tip and dorsum of the tongue were positioned
      anteriorly and inferiorly at rest and during the buildup of negative intraoral
      pressure. The dorsum of the tongue tended to move and be positioned anteriorly as
      the tongue tip protruded and pushed the maxillary and mandibular anterior teeth.
      The tongue tip traveled a significantly smaller distance from the stage of tongue
      rest position to that of most retruded tongue tip position and a significantly
      larger distance from the stage of most retruded tongue tip position to that of
      tongue tip fixation in open bite patients than in controls.

PMID- 14694829
TI  - Effects of a mixed infection with Porphyromonas gingivalis and Treponema
      denticola on abscess formation and immune responses in mice.
AB  - Porphyromonas gingivalis and Treponema denticola have been found together in
      lesions of human periodontitis. We examined the ability of a mixed infection by
      both bacteria to synergistically form abscesses and disturb immune responses in
      mice. Absorbance of an invasive P. gingivalis 16-1 strain grown in tryptic soy
      broth and T. denticola ATCC 33520 strain grown in TYGVS medium were adjusted.
      BALB/c mice were injected with 200 microliters of the cell suspension at a site
      on the lateral dorsal area. The sizes of the subsequent subcutaneous abscesses
      were measured with a caliper gauge, and the area was expressed in square mm.
      Mixed infections by P. gingivalis and T.denticola produced larger abscesses than
      those formed after mono-infections by either P. gingivalis or T.denticola. The
      abscesses caused by mixed infection reached their maxima on the 6th day and
      maintained that size for the subsequent 5 days. The delayed type
      hypersensitivities against extracted antigens of P.gingivalis in mixed infection
      mice were significantly lower than those in the mono-infected mice. However, the
      IgG response to sonicated antigen of P.gingivalis did not differ between the two
      groups. The sizes of the abscesses caused by mixed infections in mice immunized
      with whole cells of P.gingivalis 16-1 were compared to those caused in sham
      immunized mice. The average size of the abscess caused by mixed infection in
      immunized mice did not differ from that in sham-immunized mice, but many of the
      abscesses in immunized mice ruptured on the 4th or 5th day, followed by recovery
      in two weeks. These results suggest that mixed infection with P.gingivalis and
      T.denticola attenuates protective immune responses.

PMID- 14694830
TI  - Implication of responses to bacterial heat shock proteins, chronic microbial
      infections, and dental metal allergy in patients with pustulosis palmaris et
      plantaris.
AB  - Pustulosis palmaris et plantaris (PPP) is a chronic relapsing skin disease
      characterized by sterile intraepidermal pustules and, usually, by scaly
      erythematous skin on the palm, soles, or both. To determine the primary
      pathogenic factors involved in the onset of PPP, we analyzed the implications of
      heat shock proteins (HSPs), which are highly conserved immunogenic proteins,
      chronic microbial infections including marginal and periapical periodontitis, and
      delayed type hypersensitivity (DTH) against dental metals examined by patch
      tests. We found that the titers of IgG against HSPs of Escherichia coli GroEL and
      Actinobacillus actinomycetemcomitans DnaJ in the sera from PPP patients were
      higher than those in the control group (GroEL; p < 0.05). Two patients with PPP
      had more than 1,000 ng/ml serum IgE level. We found that the average serum IgG
      antibody level against human cytomegalovirus (HCMV) in the PPP patient group was
      higher than that of the healthy group (p < 0.05). DTH against dental metal was
      found in eight of 22 PPP patients. Six of eight patients reacted against more
      than two metals. Replacement of dental metal with resin in these patients
      resulted in the disappearance or remission of PPP. These findings suggest that
      the immune responses to HSPs produced by oral bacteria, HCMV infection, dental
      metal allergy, and their combinations are etiological factors for PPP. We
      concluded that various kinds of examinations, including oral cavity conditions
      and chronic infections, are essential to determine the major etiologic factors of
      PPP.

PMID- 14694831
TI  - Clinical validity of the interactive and low-dose three-dimensional dento
      alveolar imaging system, tuned-aperture computed tomography.
AB  - Based on technical studies and clinical examinations, the clinical value of a new
      three-dimensional dento-alveolar imaging system, Tuned-Aperture Computed
      Tomography (TACT), were examined for dental applications. TACT is a conventional
      and low-cost tomosynthesis method in which the benefit of digitization is fully
      utilized. The clinical information yield of TACT has been examined for the
      detection of dental caries, periodontal defects and radicular fractures, and also
      for the pre-surgical assessment of implant placement and impacted teeth. In this
      article, we introduce basic TACT technology, review the literature pertaining to
      in vitro and in vivo studies, and describe the outline of our study of TACT to
      determine its clinical value in the assessment of impacted maxillary teeth.

PMID- 14694832
TI  - Clinical evaluation of osseointegrated implants in Tokyo Dental College Hospital
      (third report): long-term observation of functioning survival rate of fixtures.
AB  - The objective of this report was to review 365 cases of Branemark Implant Bridge
      including 1,444 fixtures in patients of Tokyo Dental College Chiba Hospital. The
      term of implantation was divided into several phases; less than 1 year, from 1
      year to 3 years, from 3 years to 5 years, from 5 years to 7 years, from 7 years
      to 10 years, more than 10 years, and the survival rate was calculated for each
      phase. The removal rate of fixture after connecting the superstructure was 13% in
      maxillary cases and 2% in mandibular cases. The functioning survival rate in
      maxillary cases slightly decreased from 91% in less than 1 year to 87% after more
      than 10 years; however, the functioning survival rate in mandibular cases was
      about 99% in all periods. The removal rate of fixtures per patient was 23% in
      maxillary cases and 6% in mandibular ones. The average removal number of fixtures
      was 1.8 in maxillary cases and 1.2 in mandibular ones. The removal of the fixture
      occurred most frequently at less than 1 year in maxillary cases, but there was no
      tendency for a pattern of removal of fixture in mandibular cases.

PMID- 14694833
TI  - [Reduction of cardiovascular risk--a new approach in therapy of type 2 diabetes].

PMID- 14694834
TI  - [Acarbose, a reliable therapeutic principle].
AB  - Acarbose is a first-line treatment for newly diagnosed patients with type 2
      diabetes, those who have high postprandial blood glucose and for patients in whom
      dietary treatment alone provides inadequate glycemic control. Acarbose lowers
      blood glucose when administered as monotherapy and in combination with other
      antidiabetic drugs. It reliably reduces levels of glycated hemoglobin (HbA1c) by
      0.9% and positively affects other parameters of the metabolic syndrome. In
      patients with impaired glucose tolerance, it reduces cardiovascular endpoints
      significantly by 49%. There are no serious side effects. Gastrointestinal adverse
      effects decrease considerably by a stepwise and individual dosage adjustment
      during long-term treatment and good dietary discipline.

PMID- 14694835
TI  - [Postprandial blood glucose as the driving force in pathogenesis of type 2
      diabetes].
AB  - Diabetes mellitus type 2 develops worldwide in the dimensions of an epidemic
      disease. In order to reduce the personal burden of patients and the enormous
      costs for the health system, which are mainly due to diabetes complications,
      diabetes prevention is urgently needed. Regarding pathophysiology, type 2
      diabetes develops on the basis of insulin resistance, together with increasing
      reduction of insulin secretion. This leads to postprandial blood glucose peaks
      (Impaired Glucose Tolerance, IGT), which furthermore increase insulin resistance
      (metabolic resistance) and decrease insulin secretion, finally resulting in
      manifestation of diabetes mellitus. Therefore it is a logical way of diabetes
      prevention, to treat postprandial blood glucose peaks in the early stadium of
      IGT. The STOP-NIDDM trial showed conclusively that acarbose reduces postprandial
      hyperglycemia and diabetes incidence for 36% in comparison to placebo in a group
      of IGT patients. At the same time the incidence of normal glucose tolerance
      increased significantly for 30%. The NNT ("number needed to treat") for acarbose
      to avoid one case of diabetes manifestation in patients with IGT, is eleven
      patients in 3.3 years. The preventive effect of acarbose is independent of age,
      gender or weight of the patients. So acarbose has the potential to reduce
      postprandial hyperglycemia, which is the driving force for diabetes, and thus can
      prevent diabetes mellitus type 2.

PMID- 14694836
TI  - [Does targeted therapy of type 2 diabetes prevent cardiovascular incidents?].
AB  - An impaired glucose tolerance results in a significantly increased cardiovascular
      risk. In view of the dramatically increasing population with non-insulin
      dependent diabetes mellitus, metabolic syndrome and impaired glucose tolerance,
      new therapeutic options are urgently required. In the past, studies of an
      intensified diabetes therapy generally did not reveal a relevant effect on the
      incidence of macrovascular complications. Consequently, the phrase of the
      "glucose paradoxon" was coined. The STOP-NIDDM study (study to prevent non
      insulin-dependent diabetes mellitus) for the first time showed a reduction of
      cardiovascular events by 49% in patients with impaired glucose tolerance treated
      with acarbose compared with placebo. Furthermore, a retrospective metaanalysis of
      seven placebo-controlled long-term-studies of acarbose in patients with non
      insulin-dependent diabetes mellitus showed a reduction of cardiovascular events
      by 41% (p = 0.0017). In summary, there is good evidence from placebo-controlled
      studies of a significant reduction of cardiovascular risk by acarbose in patients
      with impaired glucose tolerance or non-insulin-dependent diabetes mellitus.

PMID- 14694837
TI  - [From cardiovascular risk to chronic heart failure].

PMID- 14694838
TI  - [Awards for research and development of acarbose].

PMID- 14694839
TI  - [Diabetes mellitus, cardiovascular sequelae and acarbose. Introductory Address by
      the German Diabetes Society].

PMID- 14694840
TI  - [Prevention and early therapy play too minor a role in our health care system].

PMID- 14694841
TI  - [30 years Journal of Pediatric and Adolescent Pschiatry and Psychotherapy].

PMID- 14694842
TI  - [Analysis of EEG coherence in examination of an automation deficit in reading
      spelling disorder--a pilot study].
AB  - OBJECTIVES: Do dyslexic children exhibit a general automatizational deficit as
      well as a phonological deficit? METHODS: In 16 children aged 9-11 years the
      reaction time, the number of mistakes and EEG (19 scalp electrodes) were measured
      in three experiments (verbal and nonverbal). The EEG data was baseline-corrected
      and after a fast fourier transformation, analyzed with the coherence tool of the
      Brainvision Software. RESULTS: The dyslexic group made more mistakes than the
      control group on all tasks but their reaction times were significantly longer
      only on the verbal tasks. There were no coherence differences on the nonverbal
      task. On the language-dependent tasks the dyslexics showed higher total-frontal
      and lower left-frontal coherences only in the theta-frequency range, while in the
      alpha and beta frequency ranges coherences did not differ. CONCLUSIONS: A
      language-dependent cognitive automatizational deficit in the dyslexic group is
      assumed that is depicted by the higher synchronization of total-frontal
      coherences (involvement of the central executive) and is based on the less
      established functional coupling of cortical subsystems for language processing.

PMID- 14694843
TI  - [Follow-up of a sample of children with reading-spelling disorders in adulthood].
AB  - OBJECTIVE: Only a few studies--especially in Germany--deal with the long-term
      outcome for dyslexic children. The aim of our study was to assess a group of
      former students of a boarding school for dyslexic children (Chrisophorus School
      Oberurff). METHODS: 29 adults with spelling disorder were examined 20 years after
      they had left school. Their spelling ability was measured with the Mannheimer
      Spelling Test (MRT), psychiatric symptoms with the Symptom Checklist by Derogatis
      (SCL-90), occupational status with the Wegener "Magnitude-Prestigeskala"
      (Magnitude of Prestige Scale), and intelligence with the Culture Fair
      Intelligence Test (CFT 20). A self-constructed questionnaire was used to assess
      subjects' self-perception of their reading and spelling abilities, the role of
      reading and spelling in their work, and the influence of reading and spelling on
      their choice of employment. RESULTS: Spelling skills at follow-up were more than
      0.5 standard deviations above the spelling skills measured at school. The
      occupational status is rather high at 75% above average. There is no evidence of
      a significant load of psychiatric symptoms among the dyslexic adults.
      CONCLUSIONS: The general finding is a favorable development of children with
      spelling disorder 20 years after attendance at a special boarding school for
      dyslexic children. High IQ, the high socioeconomic status of the probands and
      their parents, and the long-lasting remedial work at school are most likely the
      relevant factors for this development.

PMID- 14694844
TI  - [Change in muscle strength in patients with anorexia nervosa during inpatient
      treatment--a pilot study].
AB  - OBJECTIVE: Changes in muscular strength during treatment of inpatients suffering
      from anorexia nervosa were to be documented by exact measurement. METHODS: The
      maximum strength of each side of the body was measured in 10 patients in the 1st,
      2nd, 3rd, 4th, 6th, 8th and 10th weeks of inpatient treatment by means of a
      series of four different exercises. A well-established measurement technique,
      including the computer program "Quantitative Muscle Assessment", was used. All
      patients showed comparable symptoms of an anorexia nervosa, restricting type
      before admission (pure food restriction without over-exercising). RESULTS: A
      polyphase course of the restitution of muscular strength could be seen in all
      patients. Since it is easily applied, the exercise "handigrip" has been used
      frequently elsewhere. In our study it failed to show a consistent development, in
      contrast to other muscle groups studied. Differences between the left and right
      sides could not be observed. CONCLUSIONS: Patients with anorexia nervosa showed
      an objectively comparable inter-individual polyphase increase in the maximum
      strength of the muscles under investigation during weight restitution.

PMID- 14694845
TI  - [ICD-10 diagnosis and quality of life. A pilot study of quality of life of
      children and adolescents with psychiatric disorders].
AB  - OBJECTIVE: The present study examined whether the quality of life in children and
      adolescents with psychological disorders, as judged by the patients themselves
      and their mothers, differed according to the various ICD-10 diagnoses or the
      number of axes involved. METHODS: 151 children/adolescents and 125 mothers,
      referred consecutively to the clinic, completed the Inventory for Evaluation of
      Quality of Life in Children and Adolescents (Inventar zur Erfassung der
      Lebensqualitat bei Kindern und Jugendlichen; ILK) by Mattejat et al. ICD-10
      diagnoses were grouped for evaluation. RESULTS: No significant interaction
      between the five diagnostic axes and the several domains of quality of life was
      found. However, mothers of children and adolescents with attention
      deficit/hyperactivity disorders and/or conduct disorder more often tended to
      judge their children's quality of life as unsatisfactory in all domains, while
      the patients themselves did not. Thus, rather than the children themselves it
      seems to be the children's environment which considers "external disorders" to be
      distressing. CONCLUSIONS: The authors conclude that the quality of life as
      measured by the ILK cannot be captured by ICD-10 criteria. Apparently it is not
      so much the diagnosis itself but its subjective meaning that has the most
      essential impact on an individual's assessment of quality of life.

PMID- 14694847
TI  - [The Irlen syndrome--are there pathophysiologic correlates and scientific
      evidence for "reading with colors"?].

PMID- 14694846
TI  - [Quality of life of children and adolescents with psychiatric disorders. Results
      of the 1st multicenter study with an inventory to assess the quality of life in
      children and adolescents].
AB  - OBJECTIVE: A newly developed, disorder-nonspecific instrument to measure the
      quality of life in children and adolescents (ILK, Mattejat et al., 1998) was
      tested with regard to its ability to differentiate between psychiatric in- and
      outpatient samples. METHODS: 626 children and adolescents from regionally
      different in- and outpatient clinics completed the ILK questionnaire. The data
      obtained were first described and then analyzed by means of logistic regression
      analysis. RESULTS: Whereas the descriptive analysis revealed that inpatients
      evaluated all areas of life more unfavorably than outpatients did, the logistic
      regression analysis modified these results. It became evident that some of the
      findings obtained were due to the effects of age and/or gender. However, given
      age and gender as covariates, there still remained some important life domains in
      which inpatients were more impaired than outpatients. CONCLUSIONS: The ILK turned
      out to be an efficient and economic instrument to measure the quality of life in
      children and adolescents depending on the severity of their disorder. Moreover,
      it is sensitive to effects of age and gender. As the ILK is able to reliably
      identify areas with a reduced quality of life, it offers valuable starting points
      for indications, therapy planning and initial therapeutic interventions.

PMID- 14694848
TI  - Patient-derived fibrin sealant: clinical, preclinical, and biophysical aspects.
AB  - Today, there is an enormous interest in surgical sealant, not only for
      hemostasis, but also for binding of tissues together during surgery, and to
      improve wound healing. Man has imitated nature in developing fibrin sealant that
      is biodegradable. However, the risk of transmission of both known and unknown
      infectious agents can generally not be ruled out completely for plasma products
      from donors. In addition there is a considerable immunologic risk of using
      biological products of animal origin. Preclinical and clinical data has
      demonstrated that a safe and useable surgical fibrin sealant can be prepared from
      the patient's own blood using the enzyme batroxobin. Experimental data showed
      that patient-derived fibrin sealant provided enhanced instant adhesion strength
      and elasticity compared with conventional fibrin sealant due to its faster
      polymerisation rate. Test methods for fibrin sealant were found to be inaccurate,
      and we constructed and validated a new computer assisted test method to get
      information about elasticity and other dynamic properties of biological sealant.
      The method is highly reproducible and is the first validated using vital human
      tissue as the adhesion substrate. It takes about one half hour to prepared
      patient-derived fibrin sealant, which may turn a good operation into a perfect
      operation without any known risk.

PMID- 14694849
TI  - The pharmacokinetics and pharmacodynamics of progastrin-derived peptides.
AB  - The elimination of progastrin-derived peptides was a first-order process, also at
      supraphysiological concentrations in plasma. The site of extraction was dependent
      on the molecular size of the peptides and not on their bioactivity. Apart from
      the kidneys and brain, where the extraction was nonselective, elimination was
      found in the gastrointestinal tract and limb (Gastrin-17, Gastrin-17 Gly and
      Gastrin-6). The porcine liver eliminated postprandial gastrin, while human
      gastrin except gastrin-6 passed unhindered. Metabolism of circulating gastrin was
      neither recorded in the lungs nor in the heart. In the kidneys peptides were
      mainly metabolized rather than excreted, since the recovery of intact peptide in
      urine was minimal. However, urinary clearance varied with the molecular form of
      the peptides under influence of glomerular filtration and handling in the renal
      tubules. Thus, N-terminal fragments had a higher urinary clearance than C
      terminal peptides. Gastrin degrading enzymes were present in human and porcine
      plasma, but their contribution to whole-body metabolism was small. It is
      concluded that there is a differential metabolism of progastrin products in the
      vascular beds of which the integrated metabolism in nonorgan tissue such as limbs
      and trunk accounts for the major part of whole-body clearance.

PMID- 14694850
TI  - Candidate genes and late-onset type 2 diabetes mellitus. Susceptibility genes or
      common polymorphisms?
AB  - Several lines of evidence suggest that the aetio-pathogenesis of the common form
      of type 2 diabetes mellitus and its intrinsically related features of impaired
      insulin secretion and decreased insulin sensitivity (insulin resistance) includes
      a strong genetic component. At present, however, little is known about the nature
      of this genetic component although familial clustering of the disease has been
      described for decades. Major break-throughs in the genetic sciences of type 2
      diabetes have been identifications of insulin receptor gene mutations in
      syndromes of severe insulin resistance and mutations in pancreatic beta-cell
      genes in the monogenic sub-group of type 2 diabetes: maturity-onset-diabetes-of
      the-young, MODY. Pathophysiological models of insulin resistance in skeletal
      muscles and impaired glucose-induced insulin secretion in the beta-cells have
      formed a basis for selecting candidate genes with potential influence on the
      development of type 2 diabetes ("diabetogenes"). This process of selecting and
      analyzing genes for mutations that potentially associate with either type 2
      diabetes mellitus, insulin resistance or impaired insulin secretion is often
      described as the "candidate gene approach". The studies reported in this thesis
      are excerpts from an extensive strategy of genetically dissecting (mutation
      analysis) in: 1) patients with the common form of late-onset type 2 diabetes
      mellitus the pathways that transduce the insulin signals from the plasma membrane
      to the activation of glycogen synthesis in skeletal muscle, and in 2) patients
      with either late-onset type diabetes or MODY the pathways involved in normal beta
      cell development and beta-cell function (insulin secretion). Twelve of the genes
      that encode proteins in the insulin-signalling pathway from the insulin receptor
      through the phosphatidylinositide-regulated kinases down to the complex of
      phosphatases that regulate glycogen synthesis in skeletal muscle were analyzed.
      We could not confirm that a Val985Met variant in the insulin receptor is
      associated with type 2 diabetes or that the Met326Val of the p85 alpha regulatory
      subunit of the phosphoinositide-3 kinase is associated with insulin resistance.
      We found no coding mutations (missense) in the insulin signalling protein kinases
      but we confirmed that the 5 bp deletion (PP1ARE) in the 3'-end of the PPP1R3 gene
      that encodes the glycogen-associated regulatory subunit of protein phosphatase-1
      (PP1G) is associated with insulin resistance estimated as insulin mediated
      glucose uptake. In contrast to protein kinases in skeletal muscles the genes
      encoding beta-cell transcription factors (IPF-1, NeuroD1/BETA2, and Neurogenin 3)
      are polymorphic but we could not confirm that the Asp76Asn of IPF-1 is a
      susceptibility gene for late-onset type 2 diabetes. On the other hand we
      confirmed that the Ala45Thr variant in NeuroD1/BETA2 may represent a
      susceptibility gene for type 1 diabetes but none of these genes revealed any MODY
      specific mutations. Also the gene encoding the ATP-regulatable potassium channels
      of the beta-cell (Kir6.2) is polymorphic but none of these polymorphisms
      associated with changes in glucose-induced insulin secretion. Reviewed in context
      of the existing data our studies support the candidate gene approach as a
      feasible method for directly either identifying or excluding any gene as a
      diabetes-susceptibility gene ("diabetogene").

PMID- 14694851
TI  - n-3 fatty acids and the risk of sudden cardiac death. Emphasis on heart rate
      variability.
AB  - Marine n-3 PUFA have potential antiatherogenic, antithrombotic, and
      antiinflammatory properties. However, recent research have addressed the
      antiarrhythmic effect of these fatty acids as a major explanation for their
      beneficial role in IHD and such an effect may explain the reduction in the
      incidence of SCD observed among fish eaters. SCD remains a serious problem in the
      Western Countries and although prevention of SCD is one of the main targets in
      modern cardiology the incidence of SCD has not declined during the past decades.
      Therefore, there is a need for other approaches to reduce the incidence of SCD.
      Thus, the aims of this study were 1) to study the impact of n-3 PUFA on 24-hour
      HRV, a recognized predictor of arrhythmic events and SCD in high-risk patients
      and in healthy subjects, and 2) to review the current knowledge about n-3 PUFA
      and the risk of SCD in humans and the proposed actions of n-3 PUFA responsible
      for an antiarhythmic effect. Subjects eating a modest amount of marine n-3 PUFA
      have an approximately 50% reduction in the risk of SCD compared to subjects not
      eating fish and in one study there was a close negative association between the
      risk of SCD and the cellular level of n-3 PUFA. Two large intervention studies
      support a beneficial effect of n-3 PUFA on the risk of SCD. In the DART study
      from 1989 a significant 29% reduction was found among post-MI men advised to eat
      fatty fish twice a week compared to those not advised so. This reduction could
      not be explained by an antiatherosclerotic or an antithrombotic effect of n-3
      PUFA and an antiarrhythmic effect was considered operative. Ten years later the
      GISSI Prevenzione trial showed a 45% reduction in SCD among post-MI patients
      given one fish oil capsule daily (equal to 0.85 g of n-3 PUFA). The mechanisms
      behind the protection against SCD from marine n-3 PUFA have mainly been addressed
      in animal and in-vitro studies in which n-3 PUFA have shown profound
      antiarrhythmic effects. Based on the emerging hard end point data on the effect
      of n-3 PUFA on SCD in humans it is of importance to investigate if n-3 PUFA have
      actions in humans comparable to data from non-human studies. A surrogate for the
      risk of developing ventricular arrhythmias and SCD in humans is 24-hour HRV.
      Thus, in patients with IHD the risk of malignant ventricular arrhythmias and SCD
      is increased with decreased HRV. On the opposite, pharmacological interventions
      resulting in an improved patient survival have been associated with an increased
      HRV. In our studies we found positive associations between the cellular levels of
      marine n-3 PUFA and HRV in post-MI patients and in patients referred for coronary
      angiography suspected of IHD. Also, in these patients cellular levels of marine n
      3 PUFA were independently correlated with HRV. When post-MI patients were given
      5.2 g of marine n-3 PUFA daily for 12 weeks their HRV significantly increased.
      These findings may help explain why marine n-3 PUFA offer protection against SCD
      in patients with IHD. Patients with CRF and patients with DM comprise patient
      populations with an increased risk of SCD and an attenuated HRV. In these two
      groups of patients we found a close positive association between the cellular
      level of marine n-3 PUFA and HRV suggesting a beneficial effect of marine n-3
      PUFA on HRV. Further research with dietary intervention with n-3 PUFA to CRF and
      DM patients should clarify if this effect can be translated into a reduction of
      coronary events. A decreased HRV may predict a poor outcome among healthy
      subjects due to an increased risk of SCD. We found a close positive association
      between cellular levels of marine n-3 PUFA and HRV in healthy men but not in
      healthy women. Dietary intervention with either 2.0 g or 6.6 g of marine n-3 PUFA
      daily for 12 weeks revealed a dose-dependent increase in HRV among men with a low
      base-line HRV. The results may help explain why dietary marine n-3 PUFA may
      reduce the risk of SCD in healthy men. It is a novel observation that n-3 PUFA
      have a beneficial impact on HRV in humans. The results from non-human studies
      showing effects of n-3 PUFA on sodium channels, calcium-channels and adrenergic
      receptors may, if applicable to humans, explain this effect of n-3 PUFA on HRV.
      However, n-3 PUFA may also cause a central modulation of HRV and, n-3 PUFA may
      thus modulate HRV both at the level of the brain and in the heart. In conclusion,
      the data suggest that marine n-3 PUFA have a beneficial impact on HRV in patients
      at high risk of SCD and in healthy men. Furthermore, our data may indicate that
      the protective effect of n-3 PUFA on SCD found among post-MI patients and healthy
      subjects is caused by a modulation of autonomic control with increased vagal
      tone. Therefore, given the safety and low cost of implementing a modest amount of
      marine n-3 PUFA in the diet, an adequate dietary fish intake may have a
      significant role to play in the primary and secondary prevention of out-of
      hospital SCD.

PMID- 14694852
TI  - Blood transfusion-induced immunomodulation--is storage time important?

PMID- 14694853
TI  - Colonic absorption and metabolism of fatty acids.

PMID- 14694854
TI  - Diabetic nephropathy. Aspects of pathophysiology and treatment.

PMID- 14694855
TI  - Staphylococcus aureus bacteremia.
AB  - Staphylococcus aureus bacteremia (SAB) is still associated with a high mortality,
      and knowledge on risk factors and the clinical and the therapeutic aspects of SAB
      is still limited. This thesis focuses on the clinical aspects of SAB and its
      metastatic infections. In a study of all patients with bacteremia in Copenhagen
      County October 1992 through April 1993 (study I) we emphasized previous findings,
      that S. aureus is one of the most frequent pathogens in bacteremia, and in a case
      control study also in Copenhagen County 1994-95 (study II) we demonstrated, that
      not only an inserted central venous catheter and nasal S. aureus carriage but
      also hyponatremia and anemia are important risk factors for hospital-acquired SAB
      (study II). Studies on the treatment of SAB have pointed out, that the
      eradication of a primary is important, but there are only limited clinical
      studies dealing with antibiotic treatment. By logistic regression analysis, we
      were able to demonstrate that focus eradication is essential, but also that
      treatment with dicloxacillin 1 g x 4 or 2 g x 3 are superior to 1 g x 3 (studie
      III), indicating that the time for serum concentration above the Minimal
      Inhibitory Concentration (MIC) for the bacteria plays a role in the outcome of
      SAB treatment. S. aureus osteomyelitis secondary to SAB is frequently observed.
      No other countries, however, have a centralized registration, which make it
      possible to evaluate a large number of these patients. Since 1960, The
      Staphylococcal Laboratory, Statens Serum Institut in Copenhagen, has registrated
      selected clinical informations from nearly all patients with positive blood
      cultures of S. aureus. Based on this registration, we were able to show an
      increased number of S. aureus osteomyelitis among older patients and a decreased
      number of S. aureus osteomyelitis of femur and tibia among younger infants in the
      period 1980-90 (study IV). By reviewing the records of a large number of patients
      with vertebral S. aureus osteomyelitis, we could evaluate important aspects in
      the diagnosis and treatment of these patients (study V). We illustrated, that
      symptoms and laboratory findings were relatively unspecific, and CT-scanning or
      bone scintigraphy were absolutely necessary for the diagnosis (study V). The
      relatively high number of patients in the study allowed us to evaluate different
      treatment regimens, and we found, that treatment with penicillinase-stable
      penicillins four grams daily for at least eight weeks was necessary (study V). S.
      aureus meningitis is relatively uncommon and most often a neurosurgical infection
      based on the presence of a catheter. Meningitis secondary to SAB is relatively
      rare. The nationwide registration on Statens Serum Institut enabled us to study a
      large number of patients with special emphasis on clinical, outcome and treatment
      (study VI). We found, that these patients often were older people with chronic
      underlying diseases, the infection developed as a community-acquired infection,
      and the patients also had an unknown focus of infection. Furthermore, these
      patients often had other secondary manifestations such as endocarditis or
      osteomyelitis and an extremely high mortality (study VI). Finally, I believe that
      our studies will contribute to reduce the incidence of SAB and improve the
      diagnosis and treatment of SAB in the future.

PMID- 14694856
TI  - Geriatric rehabilitation as an integral part of geriatric medicine in the Nordic
      countries.
AB  - OBJECTIVES: First, to outline the theoretical and practical framework for
      geriatric rehabilitation in the Nordic countries and second, to survey the
      scientific medical publications for evidence-based geriatric rehabilitation.
      METHODS: Brainstorming on geriatric rehabilitation in a working group of Nordic
      teachers in geriatric medicine. Papers on scientific programmes for geriatric
      rehabilitation from Internet sources were collected and analyzed. All articles
      describing randomized studies in geriatric rehabilitation were selected for meta
      analyses. The papers were divided into four groups according to diseases,
      infirmity and resource settings: stroke, hip-fractures, acute admissions and
      programmes conducted in nursing homes, day hospitals and home services. RESULTS:
      The literature survey included 30 scientific studies (9496 patients) in
      randomized trials with valid endpoints. Geriatric rehabilitation programmes for
      stroke patients in geriatric settings (six papers, 1138 patients) reduced
      mortality and the need for nursing home placement, but the outcome for ADL
      function was not significantly changed. Function and length of stay varied
      between the studies. The outcome of geriatric rehabilitation was even more
      decisive in the randomized hip-fracture studies (seven articles, 2414 patients):
      the readmission rate and cost were significantly better. Ten studies were found,
      comparing the outcome of acute admissions of frail elderly patients (4683) with
      either geriatric (GEMU, GRU) or general medical wards. The effect of
      rehabilitation regarding mortality rate at one year, placement in a nursing home,
      physical function, contentment with services, readmission rate and cost was
      significant improvement in the geriatric settings. Internal comparisons of
      geriatric programmes in nursing homes, day hospitals and in-home services (seven
      studies, 1261 patient) revealed some differences in outcomes regarding function,
      contentment and costs. CONCLUSION: Specialized geriatric rehabilitation is
      complicated but effective when properly performed. Interdisciplinary teamwork,
      targeting of patients, comprehensive assessment and intensive and patient
      targeted rehabilitation seem to characterize the most effective programmes.
      Rehabilitation of frail elderly people poses a major future challenge and has to
      be developed further for the sake of elderly people's quality of life as well as
      economic reasons.

PMID- 14694857
TI  - Evidence suggests diabetes outcomes linked to homocysteine.

PMID- 14694858
TI  - Making peace with fluid. Social workers lead cognitive-behavioral intervention to
      reduce health-risk behavior.

PMID- 14694859
TI  - Preparing tomorrow's RNs today.

PMID- 14694860
TI  - Nursing research meets the frontline.

PMID- 14694861
TI  - How to choose the right treatment and dressing for the wound.

PMID- 14694862
TI  - Keeping i.v. therapy safe with needleless systems.

PMID- 14694863
TI  - Helping your patient choose the right blood glucose meter.

PMID- 14694864
TI  - "Backbone of the institution".

PMID- 14694865
TI  - Has nursing lost its heart?

PMID- 14694866
TI  - The keys to care. Interview by Dina Leifer.

PMID- 14694867
TI  - Between the lines.

PMID- 14694868
TI  - Badge of honour.

PMID- 14694869
TI  - As seen on TV. Should food and drink advertising be banned from pre-school
      children's television?

PMID- 14694870
TI  - Selection of pain measurement tools.
AB  - BACKGROUND: Although pain measurement tools have been available for a number of
      years their reliability and validity cannot be presumed because none holds
      psychometric stability in every environment. To select the most appropriate tool
      for an individual patient, nurses need to be aware of those available and their
      limitations. This article discusses the use of selected tools with specific
      patient groups. CONCLUSION: A variety of tools are currently used for measuring
      pain, and each one has its merits and limitations. It is difficult to choose the
      most suitable tool for clinical settings in which a standard tool is to be used.
      Patient populations are diverse and can include adults of any age, with acute,
      chronic or malignant pain and cognitive or physical impairments of varying
      origin. There will be occasions when the tool used is inappropriate for an
      individual patient or a patient cannot complete the tool. Patients and nurses
      need to be educated about pain measurement tools to ensure their successful use.

PMID- 14694871
TI  - Clinical protocols for stoma care: 2. Changing an appliance.

PMID- 14694872
TI  - Hypertension.
AB  - An estimated 20 per cent of people in the UK have elevated blood pressure that
      warrants some form of treatment or monitoring. Hypertension can have serious
      consequences for patients and may result in death from coronary heart disease and
      stroke. Early intervention, patient education and lifestyle modification are
      essential for effective management of hypertension.

PMID- 14694873
TI  - Planning for your clinical placement.

PMID- 14694874
TI  - A 'cycle of empowerment': the enabling culture of birth centres.

PMID- 14694875
TI  - 'Home from home': the key to success.

PMID- 14694876
TI  - The newborn examination in birth centres.

PMID- 14694877
TI  - A compromise for change.

PMID- 14694878
TI  - Hands off! The Breastfeeding Best Start Project (2).

PMID- 14694879
TI  - Creating a scene: the work of Progress Theatre.

PMID- 14694880
TI  - Midwifery basics: care during labour. Pharmacological methods of pain relief.

PMID- 14694881
TI  - Vitamin C and preterm delivery.

PMID- 14694882
TI  - The amnesic analgesic.

PMID- 14694883
TI  - [Nobel Prize for Medicine 2003].

PMID- 14694884
TI  - A degeneracy study in the circulant and bordered-circulant approach to birdcage
      and planar coils.
AB  - A method for finding closed-form solutions for the normal mode frequencies of
      systems with circulant 2pi/2 symmetry was investigated. This method is
      particularly good for questions of degeneracy that arise when one considers
      parallel imaging techniques like SENSE and SMASH in MRI. It is applicable to
      systems that include birdcage coils as well as planar coils with the appropriate
      rotational symmetry. A proof is given that complete degeneracy of all normal mode
      frequencies is impossible when all mutual inductive couplings are included. We
      tested the method against measurements made on a planar coil array and on an 8
      element birdcage coil. The inclusion of the co-rotating end-ring mode changes the
      fundamental symmetry of the system from circulant to "bordered circulant". Closed
      form solutions for the normal mode frequencies of a bordered circulant system are
      also given.

PMID- 14694885
TI  - [Psychiatrists and the pharmaceutical industry].
AB  - Relationships between psychiatrists and the pharmaceutical industry have
      increased in frequency and intensity, both on the individual level and
      particularly on the institutional level. They extend from necessary and desirable
      cooperation to questionable practices and to unacceptable misconduct. Especially
      the latter has provoked a lively discussion and has initiated recommendations as
      well as guidelines. Their aim is to safeguard the integrity of physicians as well
      as the industry and to avoid endangering the relationship between the physician
      and the patient. They will do this by establishing clear norms, unequivocal
      documentation, and disclosure of relevant relationships in order to build up more
      mutual trust including that of the public. Based on a detailed review of the
      literature, 27 recommendations are put forward for discussion. Psychiatric
      associations should develop explicit guidelines for the relationships between
      psychiatrists and the pharmaceutical industry.

PMID- 14694887
TI  - [Qualified outpatient care facilities for the mentally ill, because of misapplied
      resources, are not yet utopia].

PMID- 14694886
TI  - [Depressive disorders with somatic illnesses].
AB  - Up to 40% of medically ill patients suffer from clinically relevant depressive
      disorders, of which almost half can be classified as major depression. Some
      modern medical treatment procedures seem to increase the risk of depression.
      Quality of life as well as influences detrimental to the course of medical
      illness can be favourably influenced by a validated diagnostic approach and early
      careful therapeutic interventions. However, treating depressive disorders does
      not seem to exert a direct influence on the somatic prognosis. High depressive co
      morbidity and burden of illness for both the individual and the society form a
      stark contrast to the obviously still insufficient diagnostic and therapeutic
      strategies in daily medical routine.

PMID- 14694888
TI  - [Mental disorders: no concoction].

PMID- 14694891
TI  - What clinicians should know about SV40 large T antigen and nucleocytoplasmic
      transport.

PMID- 14694892
TI  - Fingerprinting cancer development.

PMID- 14694893
TI  - Hercules versus the methane monster: separating law from mythology for practical
      use in disasters and emergencies.

PMID- 14694894
TI  - Multimodal assessment of the primary healthcare system of Serbia: a model for
      evaluating post-conflict health systems.
AB  - INTRODUCTION: Conflicts, social unrest, and disasters can significantly affect
      the ability of a healthcare system to provide for the needs of its citizens. The
      collapse of the primary healthcare system in Serbia is a model of the effects
      that civil unrest can have on the health of a population. However, with improving
      social and political conditions, focus now can be turned towards the greatly
      needed development and reorganization of the primary healthcare system in Serbia.
      Due to the complexity of health-system reform in the post-conflict/post-disaster
      setting, attempts to restructure health services are fraught with pitfalls that
      often are unanticipated because of inadequate preliminary assessments. A
      multimodal assessment involving quantitative and qualitative methodologies may
      provide a more robust mechanism to identify key programmatic priorities and
      critical barriers for appropriate and sustainable health-system interventions.
      The purpose of this study is to describe a multimodal assessment using primary
      healthcare in post-conflict Serbia as a model. METHODS: Integrated quantitative
      and qualitative methodologies--system characterization and observation, focus
      group discussions, free-response questionnaires, and Q-methodology--were used to
      identify needs, problems, and potential barriers to primary healthcare
      development in Serbia. Participants included primary healthcare providers and
      administrators from 13 institutions throughout Belgrade. RESULTS: Demographic
      data indicate a well-established infrastructure of primary health centers and
      stations. However, focus group discussions and free-response questionnaires
      reveal significant impediments to delivery of care: (1) Inadequate equipment,
      supplies, and medications; (2) Poor financial investment; (3) Discouraging worker
      salaries; (4) Few opportunities for professional development; and (5) Little
      emphasis on or respect for primary healthcare. Q-methodology of provider
      perceptions and opinions supports these concerns, shows remarkable consensus
      among participants, and provides further insights toward system development by
      grouping respondents into distinctive types. CONCLUSIONS: This study identified
      the critical needs and barriers to development of primary healthcare in Serbia.
      This combined methodology may serve as a model for future health system
      assessments in the post-conflict and post-disaster settings.

PMID- 14694895
TI  - Medical support for children's mass gatherings.
AB  - INTRODUCTION: Medical care must be well-planned for mass gatherings. Events such
      as fairs, concerts, parades, and rallies cause many people to gather in one
      place, increasing the chance of injuries and for the development of a disaster.
      In this study, the level and quality of medical care were evaluated at a mass
      gathering of approximately 100,000 children. The event was a television-sponsored
      fun fair. METHODS: Every patient contact was documented on printed forms,
      including data such as the number of patients treated, gender of the patients,
      presence or absence of a parental escort, time distribution of patient contacts,
      the diagnoses for the patient contacts, specific therapies applied, duration of
      the treatment, and patient discharge information. All data were coded after the
      event and transferred into a computer database. These data were analyzed using
      descriptive statistics. RESULTS: Of the 100,000 spectators, 192 patients (81 male
      [42.2%] and 111 female [57.8%]) were treated during the nine-hour period, from
      09:00 hours (h) until 18:00 h. Twenty percent of all the children up to the age
      of 10 years needing medical assistance were not accompanied by an adult. Seventy
      five percent of all patient contacts were made during the afternoon. Of those
      treated, 164 patients (85.4%) suffered only minor injuries and were seen for <10
      minutes. The most common type of complaint was minor trauma (103 patients,
      53.6%); followed by minor medical problems such as headaches or light allergic
      reactions (21 patients, 10.9%); insect bites (20 patients, 10.4%); and serious
      medical problems or trauma such as severe arterial hypertension or long bone
      fractures (19 patients, 9.9%). Treatment included, but was not limited to,
      dressings (100 patients; 52.1%), local therapy (68 patient, 35.4%), and analgesic
      therapy (10 patients, 5.2%). Four patients (2%) were transferred to local
      hospitals. CONCLUSION: Most of the medical needs in the patients attending the
      children's fun fair were minor. Nevertheless, for similar events in the future,
      the medical team should be qualified for all serious medical emergencies, as well
      as major trauma; and should be prepared to meet the requirements of the specific
      group of spectators. The overall usage rate in the children's fun fair described
      was 19.2 patient encounters per 10,000 spectators. Half of all of the patients
      were children below the age of 14 years. Medical services should consider that
      this study shows that up to 33% of children seeking medical assistance may not be
      accompanied by adults.

PMID- 14694896
TI  - Prehospital hyperventilation after brain injury: a prospective analysis of
      prehospital and early hospital hyperventilation of the brain-injured patient.
AB  - BACKGROUND: The Brain Trauma Foundation's Guidelines for the Management of Severe
      Head Injury state that the use of prophylactic hyperventilation after traumatic
      brain injury (TBI) should be avoided because it can compromise cerebral
      perfusion. The objective of this study was to assess the prevalence of
      unintentional hyperventilation. METHODS: A prospective evaluation of all
      intubated trauma patients with a diagnosis of TBI was performed. Patients with
      signs of impending herniation were excluded. RESULTS: Forty patients were
      included in the study. The average Glasgow Coma Scale (GCS) was 6.3. Of these, 28
      patients (70%) were unintentionally hyperventilated. Eleven (39%) of the
      hyperventilated patients died or were discharged in a persistent vegetative
      state. Of the remaining 12 patients who experienced normal ventilation, three
      patients (25%) died or were discharged in a vegetative state (p = ns) (Table 1).
      CONCLUSION: Hyperventilation was common after TBI. However, patients ventilated
      to a normal PaCO2 were significantly more acidotic. Prehospital personnel should
      undergo educational training after development of strict ventilation protocols
      for patients suffering TBI.

PMID- 14694897
TI  - Cost: benefit of point-of-care blood gas analysis vs. laboratory measurement
      during stabilization prior to transport.
AB  - INTRODUCTION: This study was conducted to determine whether point-of-care
      testing, using the iSTAT Portable Clinical Analyzer, would reduce time at the
      referring hospital required to stabilize ventilated pediatric patients prior to
      interfacility, air-medical transport. METHODS: The following data were collected
      prospectively: (1) When a blood gas analysis was ordered; (2) If it was necessary
      to call in a technician; (3) Waiting time for blood to be drawn; and (4) Waiting
      time for results. The cost-efficacy of point-of-care testing was calculated based
      on: (1) Three minutes for a transport team member to draw a sample and obtain a
      result using the iSTAT (unit cost 8,000 CDN dollars); (2) Lab technician call
      back (minimum two hours at 90 dollars); (3) Paramedic overtime (by the minute at
      49 dollars/hour); and (4) Cost of charter aircraft wait time (200 dollars per
      hour) for every hour beyond four hours. RESULTS: Data were collected on 46
      ventilated patients over a three month period. A blood gas analysis was ordered
      on 35 patients. Laboratory technicians were called in for 17 (49%). For 12 (34%)
      patients, there was a wait for the sample to be drawn, and for 23 (66%), there
      was a wait for results to become available. Total time waiting to obtain
      laboratory gases was 526 minutes compared with a calculated 105 minutes using
      point-of-care testing. An iSTAT cartridge cost of 420 dollars would not have been
      different from laboratory costs. Cost-saving on technician callback (1,530
      dollars), paramedic overtime (690 dollars) and aircraft time waiting charges
      (2,000 dollars) would have totaled (4,220 dollars). From this study, the cost of
      point-of-care equipment could be recouped in 101 patients if aircraft charges
      apply or 192 patients if no aircraft costs are involved. For 11 cases, ventilator
      adjustments were made subsequently during transport, and for six patients, point
      of-care testing, if in place, would have been used to optimize transport care.
      CONCLUSION: The data from the present study indicate significant cost-efficacy
      from use of this technology to reduce stabilization times, and support the
      potential to improve quality of care during air medical interfacility transport.

PMID- 14694898
TI  - Anglo-American vs. Franco-German emergency medical services system.
AB  - It has been stated that the Franco-German Emergency Medical Services System (FGS)
      has considerable drawbacks compared to the Anglo-American Emergency Medical
      Services System (AAS): 1. The key differences between the AAS and the FGS are
      that in the AAS, the patients is brought to the doctor, while in the FGS, the
      doctor is brought to the patient. 2. In the FGS, patients with urgent conditions
      usually are evaluated and treated by general practitioners in their offices or at
      the patient's home; initially, very few approach an emergency department. 3.
      Emergency patients with life-threatening trauma or disease are treated by
      emergency physicians at the scene and during transport. Paramedics often are
      first to arrive at the scene, and until the emergency physician arrives at the
      scene, are allowed to defibrillate, to intubate endotracheally, and to administer
      life-saving drugs (epinephrine endotracheally, glucose intravenously, etc.). 4.
      Prehospital emergency physicians treat patients at the scene and during
      transport. 5. Emergency patients are guaranteed to be reached by an appropriate
      emergency vehicle and a respective crew within 10 minutes in 80% of the responses
      and within 15 minutes in 95% of cases. 6. The FGS deploys qualified emergency
      physicians assisted by qualified paramedics as prehospital intensive care
      providers; extended immediate care is standard. Total Prehospital Times (TPT) and
      scene times only are minimally longer than in the AAS. 7. Emergency Medicine is
      recognized as a supra-specialty to the base specialties. Specific training
      programs exist for emergency physicians, medical directors of emergency medical
      services systems (EMSS), and chief emergency physicians (CEP). 8. Resuscitation
      attempts are carried out not only by anesthesiologists, but also by internists,
      surgeons, pediatricians, etc. Emergency medicine encompasses cardiopulmonary
      resuscitation (CPR) and shock cases, and patients with an acute myocardial
      infarction, stroke, poly-trauma, status asthmaticus, etc. Emergency patients are
      admitted directly to emergency departments of the hospitals, which, depending
      upon the size of the hospital. 9. The incidence of life-threatening trauma
      victims has decreased to <10% in the FGS. Of a total of 830,000 deaths/year,
      fatal trauma cases ranked the lowest at 4%. 10. Survival figures on cardiac
      arrest (asystole, ventricular fibrillation/ventricular tachycardia (VF/VT),
      pulseless electrical activity (PEA, etc.) reported in the German EMSS correspond
      to those in Europe and the United States. 11. Paramedic training is characterized
      by a two-year program followed by a theoretical and a practical examination. 12.
      Paramedics and emergency physicians-in-training are supervised at the scene and
      during transport. Quality assurance (Q/A) constitutes an integral and legally
      compulsory part of the EMSS. 13. In the majority of cases, the emergency patients
      are evaluated and treated by the respective specialties without delays caused by
      patient transfer to other hospitals. 14. The FGS does not require a greater
      number of ambulances and/or personnel than does the AAS. 15. The German
      healthcare system creates less expenses/capita than the does the U.S. system at a
      similar level of quality of care. 16. Emergency procedures are carried out by
      anesthesiologists, emergency physicians, surgeons, internists, and other
      specialists.

PMID- 14694899
TI  - Rapid epidemiological assessment of health status in displaced populations--an
      evolution toward standardized minimum, essential data sets.
AB  - Rapid epidemiological assessment (REA) has evolved over the past 30 years into an
      essential tool of disaster management. Small area survey and sampling methods are
      the major application. While REA is protocol driven, needs assessment of
      displaced populations remains highly non-standardized. The United Nations and
      other international organizations continue to call for the development of
      standardized instruments for post-disaster needs assessment. This study examines
      REA protocols from leading agencies in humanitarian health assistance across an
      evaluation criteria of best-practice attributes. Analysis of inconsistencies and
      deficits leads to the derivation of a Minimum Essential Data Set (MEDS) proposed
      for use by relief agencies in post-disaster REA of health status in displaced
      populations. This data set lends itself to initial assessment, ongoing
      monitoring, and evaluation of relief efforts. It is expected that the task of
      rapid epidemiological assessment, and more generally, the professional practice
      of post-disaster health coordination, will be enhanced by development,
      acceptance, and use of standardized Minimum Essential Data Sets (MEDS).

PMID- 14694900
TI  - Canadian Severe Acute Respiratory Syndrome (SARS) experience.

PMID- 14694901
TI  - Doctor-based basic cardiopulmonary resuscitation course.

PMID- 14694902
TI  - Fxyd3 and Lgi4 expression in the adult mouse: a case of endogenous antisense
      expression.
AB  - We have investigated the expression of Fxyd3 and Lgi4 in the adult mouse by
      Northern blot analyses and in situ hybridization. Murine Fxyd3 and Lgi4 have been
      mapped to the same locus on mouse Chromosome (Chr) 7, where the last exon of
      Fxyd3 completely overlaps with the 3'UTR in the last exon of Lgi4, which is
      transcribed in the opposite orientation. The Fxyd3 gene (formerly called Mat-8)
      encodes an 8-kDa transmembrane protein that is upregulated in mammary tumors and
      can induce a chloride conductance upon RNA injection into Xenopus oocytes. Fxyd3
      is a member of the Fxyd family of which several members are tissue-specific
      regulators of ion channels. Murine Lgi4 is a recently described member of the
      leucine-rich-repeat gene family Lgi. Northern blot analyses demonstrated a 0.6-kb
      Fxyd3 transcript with abundant expression in the murine skin, colon, and mammary
      gland, but low level expression in the brain. In contrast, a 3.2-kb Lgi4
      transcript was abundant in brain, with lower level expression in colon. Lgi4
      transcription in the skin was detectable only by RT-PCR. A Fxyd3-specific sense
      cRNA probe hybridized to a transcript in Northern blots of brain and colon RNA
      that co-migrated with the Lgi4 mRNA. In situ hybridization experiments revealed
      that both Fxyd3 and Lgi4 were expressed in the same tissue compartments in skin,
      uterus, intestine, mammary gland, and brain. These results demonstrate that Fxyd3
      and Lgi4 transcripts potentially form double-stranded RNA molecules in many cell
      types in vivo, which may impact on their respective expression.

PMID- 14694903
TI  - Comparative sequence analysis of a single-gene conserved segment in mouse and
      human.
AB  - Comparative mapping and sequencing of the mouse and human genomes have defined
      large, conserved chromosomal segments in which gene content and order are highly
      conserved. These regions span megabase-sized intervals and together comprise the
      vast majority of both genomes. However, the evolutionary relationships among the
      small remaining portions of these genomes are not as well characterized. Here we
      describe the sequencing and annotation of a 341-kb region of mouse Chr 2
      containing nine genes, including biliverdin reductase A (Blvra), and its
      comparison with the orthologous regions of the human and rat genomes. These
      analyses reveal that the known conserved synteny between mouse Chromosome (Chr) 2
      and human Chr 7 reflects an interval containing one gene (Blvra/BLVRA) that is,
      at most, just 34 kb in the mouse genome. In the mouse, this segment is flanked
      proximally by genes orthologous to human chromosome 15q21 and distally by genes
      orthologous to human Chr 2q11. The observed differences between the human and
      mouse genomes likely resulted from one or more rearrangements in the rodent
      lineage. In addition to the resulting changes in gene order and location, these
      rearrangements also appear to have included genomic deletions that led to the
      loss of at least one gene in the rodent lineage. Finally, we also have identified
      a recent mouse-specific segmental duplication. These finding illustrate that
      small genomic regions outside the large mouse-human conserved segments can
      contain a single gene as well as sequences that are apparently unique to one
      genome.

PMID- 14694904
TI  - The mouse salivary androgen-binding protein (ABP) gene cluster on chromosomes 7:
      characterization and evolutionary relationships.
AB  - Mouse salivary androgen-binding protein (ABP) is a pair of dimers, composed of an
      alpha subunit disulfide bridged to either a beta or a gamma subunit. It has been
      proposed that each subunit is encoded by a distinct gene: Abpa, Abpb, and Abpg
      for the alpha, beta, and gamma subunits, respectively. We report here the
      structures and sequences of the genes that encode these three subunits. Each gene
      has three exons separated by two introns. Mouse salivary ABP is a member of the
      secretoglobin family, and we compare the structure of the three ABP subunit genes
      to those of 18 other mammalian secretoglobins. We map the three genes as a gene
      cluster located 10 cM from the centromere of Chromosome (Chr) 7 and show that
      Abpa is the closest of the three to the gene for glucose phosphate isomerase
      (GPI) and that Abpg is the closest to the centromere, with Abpb mapping between
      them. Abpa is oriented in the opposite direction to Abpb and Abpg, with its 5'
      end directed toward their 5' ends. We compare the location of these genes with
      other secretoglobin genes in the mouse genome and with the known locations of
      secretoglobin genes in the human genome and present evidence that strong positive
      selection has driven the divergence of the coding regions of Abpb and Abpg since
      the putative duplication event that created them.

PMID- 14694905
TI  - The mapping of quantitative trait loci underlying strain differences in locomotor
      activity between 129S6 and C57BL/6J mice.
AB  - Performance in the open field and rotarod paradigms, two common assessments of
      locomotor function, have been demonstrated to be strain dependent in mice. In
      this study, eight significant quantitative trait loci (QTL) for behavior
      phenotypes in either the open field or rotarod paradigms were identified between
      the 129S6 (129/SvEvTac) and C57BL/6J strains. These strains were chosen for
      comparison because of their frequent use in the generation of mutant mice from
      gene-targeted, embryonic stem cells. Two of the QTLs for horizontal distance
      traveled are located on Chromosomes (Chrs) 1 and 12 and closely replicate the
      findings of other groups using different strains of mice. Rotarod performance was
      influenced in an oppositional manner by two separate QTLs on Chr 1 and 2.
      Additionally, examination of several different aspects of behavior in the open
      field revealed significant QTLs for average speed (Chr 12), duration (Chrs 2, 16,
      and 18), time spent in motion (Chr 16), vertical movements (rearing) (Chrs 6 and
      12), and vertical time (rearing time) (Chrs 6 and 12). Our finding of independent
      QTLs for these topographic components of open field activity supports the idea
      that they are separate and distinct from total horizontal distance traveled and
      should be studied independently. The QTLs described in this study, in combination
      with our panel of polymorphic chromosomal markers for 129S6 and C57BL/6J strains,
      will be useful in assessing the potential epistatic effects of parental strain
      background on the phenotypes of genetically modified mice.

PMID- 14694906
TI  - Mapping of taiep rat phenotype to rat Chromosome 9.
AB  - The taiep mutant rat was first described in a colony of Sprague-Dawley rats at
      the University of Puebla in 1989, with an autosomal recessive inherited pattern.
      taiep is an acronym for the progressive neurologic deficits that the rat
      develops, i.e., t = trembling (3-4 weeks), a = ataxia (at 4 months), i =
      immobility (5-6 months), e = epilepsy (5-6 months), andp = paresis (7 months
      onwards). Thus, mutant rats are first identified by a tremor at 3-4 weeks of age
      that is followed by a progressive neurological worsening (Holmgren et al. 1989;
      Lunn et al. 1997). The cause of the neurological symptoms is an early failure of
      normal myelination of the central nervous system (CNS) followed by progressive
      demyelination of certain CNS tracts (Lunn et al. 1997). We have been exploring
      the underlying pathophysiology of the mutant and have determined that the myelin
      defect results from the progressive accumulation of microtubules in
      oligodendrocytes, the myelin-producing cells of the CNS (Song et al. 1999).
      Microtubules are the major component of the cytoskeleton of this and many other
      cells of the body, and microtubule-based transport of protein and mRNA is
      essential for normal cell function. There is no direct human counterpart of the
      taiep rat. Nonetheless, providing an understanding of the control of microtubule
      dynamics in the oligodendrocyte will be highly relevant to our knowledge of the
      cell biology of the myelinating cell of the CNS. This information is of great
      relevance to the function of the cell in human myelin disorders and in
      experimental remyelination. As the taiep rat apparently has a primary disorder in
      the oligodendrocyte cytoskeleton, it is an ideal model in which to study this
      process. This information may also be a key to the complete understanding of the
      mechanism of microtubule assembly/disassembly in many cell types.

PMID- 14694907
TI  - Molecular cytogenetic analysis and centromeric satellite organization of a novel
      8;11 translocation in sheep: a possible intermediate in biarmed chromosome
      evolution.
AB  - During analysis of genome organization in sheep (Ovis aries, 2n = 54, XY/XX), we
      found a novel chromosomal translocation in an animal expected to be normal,
      adding to the six 'centric fusions' previously reported. The translocation was
      identified as t(8;11) by G-banding and was shown to be centric, involving whole
      chromosome arms by chromosome painting with probes for Chromosomes (Chrs) 8 and
      11. Satellite I and a newly isolated satellite II clone was used to characterize
      the centromeric regions of both the novel and the three pairs of evolutionarily
      derived biarmed chromosomes. The novel t(8;11) showed satellite I proximal on
      both arms with satellite II covering the centromere, while the evolutionarily
      derived fusion leading to Chrs 2 and 3 showed the opposite configuration, not
      obviously derived by a simple fusion. Chr 1 has lost the satellite I
      hybridization patterns. The novel t(8;11) provides strong evidence for an
      intermediate step in evolution of the biarmed chromosomes in sheep.

PMID- 14694915
TI  - Healing and palliative care: charting our way forward.

PMID- 14694908
TI  - A comprehensive radiation hybrid map of bovine Chromosome 26 (BTA26): comparative
      chromosomal organization between HSA10q and BTA26 and BTA28.
AB  - In this study, we present a comprehensive 3000-rad radiation hybrid (RH) map of
      bovine Chromosome (Chr) 26 (BTA26) with 80 markers including 50 genes or ESTs: 44
      have an ortholog mapping to human Chr 10 (HSA10) and 29 to mouse Chr (MMU) 7, 10,
      and 19. Moreover, 12 other HSA10 genes were integrated in a newly developed RH
      map of BTA28 (seven represent new assignments). The available draft of the mouse
      genome allowed us to present a detailed picture of the distribution of conserved
      synteny segments among the three species (human, cattle, and mouse) and to
      propose a simple model of the comparative chromosomal organization between the
      long arm of HSA10 and BTA26 and 28. Finally, the INRA bovine BAC library was
      screened for most of the BTA26 markers considered in this study to provide
      anchors for the bovine physical map.

PMID- 14694916
TI  - A randomized controlled trial of supplemental oxygen versus air in cancer
      patients with dyspnea.
AB  - CONTEXT: The symptomatic benefits of oxygen in patients with cancer who have
      nonhypoxic dyspnea are not well defined. OBJECTIVE: To determine whether or not
      oxygen is more effective than air in decreasing dyspnea and fatigue and
      increasing distance walked during a 6-minute walk test. PATIENTS AND METHODS:
      Patients with advanced cancer who had no severe hypoxemia (i.e., had an O2
      saturation level of > or = 90%) at rest and had a dyspnea intensity of > or = 3
      on a scale of 0-10 (0 = no shortness of breath, 10 = worst imaginable shortness
      of breath) were recruited from an outpatient thoracic clinic at a comprehensive
      cancer center. This was a double-blind, randomized crossover trial. Supplemental
      oxygen or air (5 L/min) was administered via nasal cannula during a 6-minute walk
      test. The outcome measures were dyspnea at 3 and 6 minutes, fatigue at 6 minutes,
      and distance walked. We also measured oxygen saturation levels at baseline,
      before second treatment phase, and at the end of study. RESULTS: In 33 evaluable
      patients (31 with lung cancer), no significant differences between treatment
      groups were observed in dyspnea, fatigue, or distance walked (dyspnea at 3
      minutes: P = 0.61; dyspnea, fatigue, and distance walked at 6 minutes: P = 0.81,
      0.37, and 0.23, respectively). CONCLUSIONS: Currently, the routine use of
      supplemental oxygen for dyspnea during exercise in this patient population cannot
      be recommended.

PMID- 14694917
TI  - The validity of EORTC QLQ-C30 fatigue scale in advanced cancer patients and
      cancer survivors.
AB  - Fatigue is a major complaint among advanced cancer patients. Several instruments
      are available for measuring fatigue. The EORTC QLQ-C30 is one of the most
      frequently used health-related quality of life (HRQOL) instruments, and it
      includes a three-item fatigue subscale. Limited knowledge exists about the
      validity, performance and sensitivity of EORTC QLQ-C30 fatigue scale as compared
      with a fatigue-specific instrument. The aim of the present study was to validate
      the EORTC QLQ-C30 fatigue scale (FA) against the Fatigue Questionnaire (FQ). The
      FQ is frequently used and was developed to measure fatigue in both cancer and
      noncancer populations. The FQ measures physical (PF, seven items) and mental
      fatigue (MF, four items). The study population included two different cohorts: A)
      patients with advanced metastatic cancer included in a prospective randomized
      study of palliative radiotherapy (n = 238); B) patients with leukaemia and
      malignant lymphoma curatively treated with stem-cell transplantation and high
      dose chemotherapy (n = 128). The analysis demonstrated that the FA correlated
      higher with the PF scale (r = 0.67-0.75) as compared with the MF scale (r = 0.49
      0.61). The item scale correlations between FA items and the PF scale were
      consistently higher than between FA items and the MF scale. A factor analysis
      including all the items within the FA and the FQ identified two factors. All FA
      items loaded on a PF factor (0.70-0.85). A floor/ ceiling effect, indicating a
      high number of respondents with lowest, respectively, highest scores was observed
      more frequently in the FA as compared with the FQ. The PF discriminated better
      between diagnostic groups with different levels of fatigue than the FA did. In
      conclusion, the EORTC QLQ-C30 fatigue scale is measuring physical fatigue. A
      floor/ ceiling effect seems to appear for the EORTC QLQ-C30 fatigue scale. The
      validity of the EORTC QLQ-C30 fatigue scale is to be questioned for use in
      palliative care patients. In studies with fatigue as a defined end point, a
      domain-specific instrument should, therefore, be added.

PMID- 14694918
TI  - The oral-to-intravenous equianalgesic ratio of morphine based on plasma
      concentrations of morphine and metabolites in advanced cancer patients receiving
      chronic morphine treatment.
AB  - To provide additional pharmacokinetic evidence for the oral-to-parenteral
      relative potency ratio of 1:2 to 1:3 for chronic morphine use in a palliative
      care setting, we determined the plasma concentrations of morphine and its major
      metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), in
      hospitalized advanced cancer patients maintained on long-term oral or intravenous
      morphine. There were significant linear correlations between daily doses of
      morphine and plasma concentrations (molar base) of morphine, M3G and M6G for both
      routes of administration. The oral-to-intravenous relative ratios of the
      regression coefficients were 2.9 for morphine and 1.8 for morphine + M6G. The
      morphine kinetic variables were not significantly influenced by any hepato-renal
      biochemical markers. These results support the commonly used oral-to-intravenous
      relative potency ratio of 1:2 to 1:3 in patients with cancer pain receiving
      chronic morphine treatment.

PMID- 14694919
TI  - Routine drug monitoring of serum concentrations of morphine, morphine-3
      glucuronide and morphine-6-glucuronide do not predict clinical observations in
      cancer patients.
AB  - The clinical importance of routine drug monitoring of serum concentrations of
      morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) during
      chronic morphine therapy is not established. We measured morphine, M6G and M3G
      serum concentrations in cancer pain patients receiving oral (n = 263, median dose
      80 mg/24 hours) or subcutaneous (sc) (n = 35, median dose 110 mg/24 hours)
      morphine. Regression analyses were performed to investigate if serum
      concentrations of morphine, M3G and M6G predicted pain intensity (Brief Pain
      Inventory), health-related quality-of-life variables (EORTC QLQ-C30) and
      cognitive function (Mini-Mental Score). Serum concentrations were also compared
      in patients categorized as morphine 'treatment successes' and 'treatment
      failures'. We observed that serum concentrations of morphine, M6G or M3G did not
      predict pain intensity, cognitive function, nausea or tiredness. 'Treatment
      failures' caused by nausea, tiredness, cognitive failure or constipation did not
      have statistically significant different morphine, M6G and M3G serum
      concentrations than patients classified as 'treatment successes'. In conclusion,
      this study did not observe any concentration-effect relationships of morphine,
      M3G or M6G with pain intensity, nausea, constipation, tiredness or cognitive
      failure in blood samples obtained during routine clinical drug monitoring in
      cancer patients. This result suggests that therapeutic drug monitoring as a
      routine tool during chronic morphine treatment has limited value for clinical
      decision making.

PMID- 14694920
TI  - Professionally perceived effectiveness of psychosocial interventions for
      existential suffering of terminally ill cancer patients.
AB  - BACKGROUND: Although integrated care for existential suffering is an essential
      part of palliative care, little is known about its concept and efficacy as
      perceived by professionals. A questionnaire survey was carried out to 1) explore
      the underlying structure of psychosocial interventions recommended by
      specialists, 2) identify the professionally perceived effectiveness of each
      intervention for specific existential distress, and 3) examine the effects of
      specialty on their recommendations. METHODS: A questionnaire with three scenarios
      representing terminally ill cancer patients with uncertainty-related anxiety,
      guilt feelings, and dependency-related meaninglessness was mailed to 701 Japanese
      psychiatrists, 118 psychologists, and 372 palliative care nurses. RESULTS: A
      total of 456 responses were obtained (response rate = 38%). Recommended
      psychosocial interventions were classified into six subcategories: 'a supportive
      expressive approach,' 'providing comfortable environments,' 'meaning-centered
      approach,' 'being,' 'education and coping skills training,' and 'a religious
      approach.' A 'supportive-expressive approach' was consistently recommended in all
      vignettes. On the other hand, 'providing comfortable environments' was most
      recommended for patients with uncertainty-related anxiety, and a 'meaning
      centered approach' and 'being' were most recommended for patients feeling
      dependency-related meaninglessness. Psychiatrists estimated the effectiveness of
      psychopharmacological treatment significantly higher than psychologists and
      nurses, while nurses evaluated efficacy of all other interventions significantly
      higher than psychiatrists and psychologists. CONCLUSIONS: Experts evaluated a
      variety of clinical interventions as effective in palliating existential
      suffering, although the perceived levels of efficacy of each intervention
      differed according to the nature of suffering and their specialties. To
      effectively alleviate existential suffering in terminally ill cancer patients, an
      integrated care by an interdisciplinary team is necessary.

PMID- 14694921
TI  - Use of complementary and alternative medicine and quality of life: changes at the
      end of life.
AB  - The purpose of this study was to compare the physical, psychological and social
      dimensions associated with quality-of-life outcomes over the last year of life,
      between advanced cancer users and nonusers of complementary and alternative
      medicine. One hundred and eleven patients were identified through Queensland
      Cancer Registry records, and followed up every four to six weeks until close to
      death using standardized protocols. Outcome measures were symptom burden,
      psychological distress, subjective wellbeing, satisfaction with conventional
      medicine and need for control over treatment decisions. At the initial interview,
      36 (32%) participants had used complementary/alternative medicine the previous
      week; mainly vitamins, minerals and tonics and herbal remedies. Among all
      participants, 53 (48%) used at least one form of complementary/alternative
      medicine over the study period. Only six (11%) visited alternative practitioners
      on a regular basis. Overall, complementary/alternative medicine users reported
      higher levels of anxiety and pain, less satisfaction with conventional medicine
      and lower need for control over treatment decisions compared with nonusers. These
      differences tend to change as death approaches. A more rigorous assessment of
      complementary/alternative medicine use, psychological distress, pain and
      subjective wellbeing among patients with advanced cancer is needed in the
      clinical setting.

PMID- 14694922
TI  - Evidence-based complementary medicine for palliative cancer care: does it make
      sense?
AB  - Complementary medicine is fast becoming an integral part of palliative cancer
      care. There is considerable debate as to whether such treatments require proof of
      effectiveness through randomized clinical trials or whether it may suffice that
      patients adopt them with apparent appreciation. We attempt to raise some of the
      arguments on both sides. The arguments include the logistical problems of
      conducting research in palliative care, ethical problems of placebo controls,
      methodological difficulties of standardizing treatments or quantifying subtle
      effects and the, often considerable, costs of clinical trials. We feel that
      neither those who argue against nor those who argue in favour of rigorous
      clinical trials are entirely wrong or entirely right. However, our final verdict
      is that an absence of rigorous science will critically hinder progress. This, in
      turn, would be to the detriment of future patients. Through discussing the
      strengths and weaknesses of both sets of arguments, both sides might learn
      valuable lessons.

PMID- 14694923
TI  - Cancer pain management in Lanarkshire: a community-based audit.
AB  - BACKGROUND: A prospective, longitudinal audit of pain management in patients with
      cancer was conducted in an unselected community population in Lanarkshire,
      Scotland. METHODS: Using a modified Delphi technique, a recording form was
      developed and a dedicated project manager was appointed to oversee the
      development and implementation of the audit. Community staff recorded pain level
      and analgesic prescribing on consecutive home visits to patients with cancer
      related pain. Areas of good and poor prescribing were assessed using standards
      previously developed for the Scottish Cancer Pain Audit. These results were fed
      back to prescribers in a variety of ways and used as a focus for a programme of
      primary care-based education. RESULTS: Five hundred and forty-one patients have
      been entered in the audit between May 1999 and end October 2002. A total of 3259
      visits have been recorded and 88% of general practices in Lanarkshire submitted
      forms during this period. Pain scores were recorded in 90% of visits. Specific
      gaps in prescribing practice were identified. CONCLUSION: The audit demonstrated
      that it is possible to engage primary care teams in a continuing audit of cancer
      pain management, which is achievable within the context of normal care. It
      provided a means to collect and analyse serial data on pain level and pain
      management and to identify areas of prescribing in need of improvement. Concerted
      efforts to establish the legitimacy and relevance of the project in the eyes of
      key stakeholders proved fundamental to encouraging longer-term behavioural change
      in the management of cancer pain.

PMID- 14694924
TI  - Severe respiratory depression and sedation with transdermal fentanyl: four case
      studies.

PMID- 14694925
TI  - Myoclonic jerks associated with gabapentin.

PMID- 14694926
TI  - The Cochrane Pain, Palliative and Supportive Care Group: life history of a
      Cochrane review.

PMID- 14694927
TI  - The double dose at bedtime study.

PMID- 14694928
TI  - Symptom prevalence in palliative care.

PMID- 14694929
TI  - Is there an additive analgesic effect of paracetamol at step 3? A double-blind
      randomized controlled study.

PMID- 14694930
TI  - Trials and tribulations.

PMID- 14694931
TI  - Right ventricular function in congenital cardiac disease: noninvasive
      quantitative parameters for clinical follow-up.
AB  - Right ventricular function is of great importance in patients with both acute and
      chronic ventricular overload. The early detection of right ventricular
      dysfunction may have an impact on therapeutic decision making, helping to prevent
      or further delay functional deterioration of the right ventricle. In patients
      with right ventricular overload due to congenital cardiac diseases, dobutamine
      stress testing combined with magnetic resonance imaging, electrocardiographic
      changes, and monitoring of concentrations of plasma brain natriuretic peptide are
      very suitable parameters for the early detection of ventricular dysfunction, and
      should therefore be used in the follow-up of these patients. It is apparent that
      no single measurement of anatomy or function can ever adequately describe the
      form or performance of the right ventricle. Rather, we should be looking more
      towards an integrated approach of different parameters for right ventricular
      function. The quantitative parameters described in this study can serve this
      purpose. The strong correlation found between these non-invasive and independent
      parameters encourages their clinical implementation.

PMID- 14694932
TI  - Safety of endomyocardial biopsy in children.
AB  - Endomyocardial biopsy in children remains important in the evaluation of
      cardiomyopathy, myocarditis, and rejection following cardiac transplantation. We
      sought to evaluate the morbidity associated with endomyocardial biopsy on the
      basis of a large experience from a single institution. We reviewed records of all
      endomyocardial biopsies performed at our institution. Complications were defined
      as adverse events resulting from the biopsy requiring intervention or additional
      observation. We also reviewed the most recent echocardiogram from all the
      patients for the presence and severity of tricuspid valvar regurgitation. Between
      November 1986 and April 2002, we performed 1051 endomyocardial biopsies in 135
      patients ranging in age from 9 days to 18 years. The internal jugular vein was
      the site of vascular access in 68% of the procedures. There were 10 acute
      procedural complications requiring intervention or additional observation. Severe
      tricuspid regurgitation developed in two patients who had undergone multiple
      biopsies after cardiac transplantation, one of whom underwent subsequent
      replacement of the tricuspid valve. There were no deaths or cardiac perforations.
      The total incidence of morbidity was 1.1%. No demographic or procedural factors
      were identified to be predictive of complications. In experienced hands,
      therefore, endomyocardial biopsy can be safely performed in children with very
      low morbidity.

PMID- 14694933
TI  - Pharmacological treatment of young children with permanent junctional
      reciprocating tachycardia.
AB  - Our objective was to assess the efficacy of pharmacological treatment in reducing
      the incidence of permanent junctional reciprocating tachycardia in young
      children, or to bring the mean heart rate over 24 h to a normal level. We
      included 21 children with a median age of 0.05 year seen with permanent
      junctional reciprocating tachycardia over the period 1990 through 2001. Of these
      children, two had abnormal left ventricular function. Follow-up visits were made
      at least every 6 months. We registered the presence of the tachycardia over 24 h,
      the mean heart rate over 24 h, and cardiac function. Treatment was started with
      propafenone alone, or in combination with digoxin as the first choice. Treatment
      was effective in 14 cases (67%), with either complete disappearance of the
      tachycardia after discontinuation of medication, or continuation in sinus rhythm
      with medication; partially effective in 4 cases (20%) when the mean heart rate
      over 24 h on the last Holter recording was less than 1 standard deviation above
      the normal for age; but was not effective in the remaining 3 cases (14%). In 3
      patients treated with propafenone, or 13 given propafenone and digoxin, treatment
      was effective in 12 (75%), partially effective in 2 (13%), and ineffective in the
      other 2 (13%). All 21 children had a normal left ventricular function at the end
      of follow-up. The median duration of follow-up was 2.4 years. Permanent
      junctional reciprocating tachycardia had disappeared spontaneously in one-third
      of the children, 5 being less than 1 year old. Adverse effects, seen in 5 cases,
      were mild or asymptomatic. No signs of proarrhythmia were registered.
      Pharmacological treatment, either with propafenone alone, or in combination with
      digoxin, is safe and effective in young children with permanent junctional
      reciprocating tachycardia. The mean heart rate is normalized, and cardiac
      function is restored and preserved. Radiofrequency ablation may be delayed to a
      safer age, with the arrhythmia disappearing spontaneously in one-third.

PMID- 14694934
TI  - Transcatheter occlusion of moderate to large patent arterial ducts, having a
      diameter above 2.5 mm, with the Amplatzer Duct Occluder. Comparisons with the
      Rashkind, buttoned devices, and coils in 116 consecutive patients.
AB  - AIM: To report results of transcatheter occlusion of moderate to large patent
      arterial ducts, having a minimum diameter above 2.5 mm, with the Amplatzer duct
      occluder, and to compare these with results achieved using Rashkind or Sideris
      devices and Cook detachable coils. DESIGN AND SETTING: Retrospective study
      conducted on intention-to-treat data from a tertiary referral centre. PATIENTS:
      Since 1989, 116 consecutive patients, 77 females and 39 males, underwent
      percutaneous closure with several devices. We used the Rashkind double umbrella
      in 23 patients, the Sideris buttoned device in 39 patients, coils in 17 patients,
      and the Amplatzer duct occluder in 37 patients. The median age of the patients
      was 37 months, and the median weight 13 kg. The mean minimum diameter of the duct
      was 3.8 +/- 1.22 mm, with a median of 3.5 mm, and range from 2.5 to 10 mm.
      RESULTS: Implantation succeeded in all but 9 of the children (92%). The time of
      fluoroscopy was shorter, and full occlusion was better as judged on angiography,
      in patients closed using the Amplatzer device, despite closure of larger ducts,
      than in patients closed using other devices (p < 0.0001, p = 0.0003, and p =
      0.0015 for the Rashkind, Sideris, and coils, respectively). Complications
      included embolisation in 2 patients, and haemolysis in 3 patients. In 12
      patients, a second device was inserted because of residual shunting noted during
      follow-up. Complete occlusion was achieved earlier after implantation (p =
      0.0002), and the rate of complete occlusion was better in patients receiving an
      Amplatzer device (97%, p = 0.024) than in patients undergoing closure with other
      devices. CONCLUSION: Transcatheter closure of moderate to large patent arterial
      ducts using the Amplatzer duct occluder is an effective and safe procedure,
      providing better results than those achieved using other occluders.

PMID- 14694935
TI  - Recommendations for the use of palivizumab as prophylaxis against respiratory
      syncytial virus in infants with congenital cardiac disease.
AB  - New data are emerging on the use of palivizumab as prophylaxis against infection
      with the respiratory syncytial virus in infants with congenital cardiac disease.
      Following a 4-year multicentre randomised trial, it was shown that prophylactic
      injections with palivizumab were effective and safe for such children.
      Prophylaxis consists of 5, monthly, intramuscular injections of palivizumab, at a
      dose of 15 mg/kg, given during the season for infection with the respiratory
      syncytial virus. Timing is at the discretion of the physician, depending on the
      onset of the season locally. It is suggested that, in the United Kingdom, this
      should be commenced in mid-September. To help clinicians to identify appropriate
      candidates for palivizumab, a working group of the British Paediatric Cardiac
      Association has developed recommendations. Infants, namely those under 1 year
      old, with congenital cardiac disease likely to benefit from prophylaxis include
      those with haemodynamically significant lesions, particularly increased pulmonary
      blood flow with or without cyanosis; pulmonary venous congestion, pulmonary
      hypertension or long-term pulmonary complications, residual haemodynamic
      abnormalities following medical or surgical intervention (patients who have
      undergone cardiopulmonary bypass should receive an injection as soon as they are
      medically stable), cardiomyopathy requiring treatment, and congenital cardiac
      disease likely to need hospital admission for medical or surgical intervention
      during the season of infection with the virus. Prophylaxis with palivizumab may
      also be indicated, at the discretion of the physician, in some children with
      complex cardiac disease over the age of 1 year. Children less likely to benefit
      from prophylaxis are those with haemodynamically insignificant disease, or those
      with lesions adequately corrected by medical or surgical intervention.

PMID- 14694936
TI  - Characterization and treatment of systemic venous to pulmonary venous collaterals
      seen after the Fontan operation.
AB  - OBJECTIVES: To determine the anatomical characteristics of systemic venous
      collaterals formed after the Fontan operation, and the efficacy of a
      transcatheter strategy for management. METHODS: We reviewed retrospectively the
      data from cardiac catherization of 50 persistently cyanotic patients after the
      Fontan operation. RESULTS: A total of 54 transcatheter interventions were
      performed, at a mean age of 6.3 +/- 3.5 years, a mean interval of 2.7 +/- 2.9
      years from completion of the Fontan circulation. Of 38 patients who had
      fenestration of the baffle at the time of surgery, 25 had patency of the
      fenestration, and 24 had the fenestration occluded with a device at the time of
      interventional treatment for associated venous collaterals. We identified a total
      of 68 systemic venous collateral channels, of which 36 (53%) were supracardiac,
      12 (18%) cardiac, and 20 (29%) infracardiac in origin. The most common site of
      origin was the brachiocephalic vein (44%), followed by the left phrenic vein
      (25%). A longer time from surgery, at 3.3 +/- 3.4 years, was associated with the
      identification of collaterals having a diameter larger than 4 mm (p < 0.01). The
      mean pulmonary arterial pressure was higher in those with larger compared to
      those with smaller collaterals (13.3 +/- 2.8 versus 11.1 +/- 2.0 mmHg, p < 0.01).
      Coils were used for occlusion of 61 vessels, and a Rashkind occluder for the
      remaining 7. After exclusion of the patients undergoing simultaneous closure of
      their fenestration, systemic saturation of oxygen increased from 89 +/- 6% to 95
      +/- 3% (p < 0.01). CONCLUSION: Venous collateral channels are common in patients
      suffering progressive cyanosis in the setting of the Fontan circulation. The
      collaterals increase in size with time, and are associated with higher pulmonary
      arterial pressures. Transcatheter treatment is feasible, and results in
      resolution of cyanosis. Only continuing follow-up will show whether further
      collateralization occurs in time.

PMID- 14694937
TI  - Subclinical rheumatic valvitis: a long-term follow-up.
AB  - In order prospectively to investigate the frequency and evolution of subclinical
      valvitis, we selected 40 consecutive patients suffering their initial attack of
      rheumatic fever, seen in our clinic from 1992 to 1994, and followed-up until
      2001, with a mean period of follow-up of 8.1 years, and a standard deviation of
      0.6 year. We also assembled a matched control group of 37 healthy children and
      adolescents. We discovered a murmur of mitral regurgitation in 28 (70.0%) of the
      patients. In 3 (7.5%) of these patients, there was also a murmur of aortic
      regurgitation. In the group of 28 symptomatic patients, Doppler echocardiography
      showed mitral regurgitation in all, and aortic regurgitation in 17. In the group
      of 12 patients without clinical evidence of cardiac involvement, Doppler
      echocardiography identified mitral regurgitation in 2, isolated in one and
      associated with aortic regurgitation in the other. Thus, the frequency of
      subclinical valvitis was 16.7%. In patients with subclinical valvitis only the
      aortic regurgitation regressed during the period of follow-up. In the group of 28
      symptomatic patients, mitral regurgitation disappeared in 6 (21.4%), aortic
      regurgitation in 7 of the 17 having this feature (41.2%), while 2 patients (7.1%)
      developed mitral stenosis. The sensitivity and specificity of cardiac
      auscultation were, respectively, 93.3%, with 95% confidence intervals between
      72.3% and 97.4%, and 100%, with 95% confidence intervals between 65.5% and 100%,
      for the diagnosis of mitral regurgitation, and 16.7%, with 95% confidence
      intervals between 4.4% and 42.3%, and 100%, with 95% confidence intervals between
      81.5% and 100%, for that of aortic regurgitation. We conclude that the Doppler
      echocardiogram is an important means of diagnosing and assessing the evolution of
      subclinical rheumatic valvar lesions, which are not always transient. We suggest
      that Doppler echocardiography should be performed in all patients with acute
      rheumatic fever. Subclinical valvitis should be considered as mild carditis,
      provided that strict criterions are observed in the differential diagnosis from
      physiological regurgitation, and Doppler echocardiographic findings are analyzed
      in the context of the other manifestations of the disease.

PMID- 14694938
TI  - The experiences with oral health and dental prevention of children with
      congenital heart disease.
AB  - OBJECTIVE: To examine the degree to which children, considered to be at risk from
      infective endocarditis, had received professional education and preventive
      procedures in regard to dental health, and to evaluate the knowledge of their
      parents of the link between oral health and infective endocarditis. MATERIALS AND
      METHODS: Questionnaires were distributed to the families of 38 children under the
      care of paediatric cardiology. A short dental examination was carried out.
      Parents were asked if they knew why oral health was of particular importance in
      their child. RESULTS: Of the children, 58% demonstrated evidence of previous or
      current dental disease, with 24% having had at least one filling, 13% with one or
      more teeth showing deficiency of enamel, and 39% with untreated dental caries.
      Only 79% of the children were registered with a dentist. According to Chi squared
      test, there was no difference in the dental health of registered and non
      registered children. Of the study group, 29% had received instruction in oral
      hygiene, 42% had received dietary advice, 13% had received advice regarding
      fluoride supplementation or had had fluoride professionally applied, and 8% had
      had fissure sealants. These percentages remained relatively low even if only
      registered children, or only registered children with previous or current dental
      disease, were considered. Only 64% of parents were aware of the link between the
      oral health of their children and infective endocarditis. Parents of children who
      were registered were more likely to be aware of this link than parents of
      children who were not registered. CONCLUSIONS: In spite of being registered with
      general dental practitioners, few children with congenital heart disease had
      received basic education in dental hygiene. Even children known to have had
      dental disease and, therefore, considered to be more vulnerable, were overlooked.

PMID- 14694939
TI  - Pulmonary regurgitation after percutaneous balloon valvoplasty for isolated
      pulmonary valvar stenosis in childhood.
AB  - OBJECTIVES: A retrospective study was undertaken to determine the degree of
      pulmonary regurgitation following percutaneous balloon valvoplasty for isolated
      pulmonary valvar stenosis. BACKGROUND: Percutaneous balloon valvoplasty is the
      recognised treatment of choice in pulmonary valvar stenosis with effective relief
      of gradient. Few studies have reviewed the degree of pulmonary regurgitation
      after the balloon valvoplasty. METHODS: We reviewed all patients with isolated
      pulmonary valvar stenosis undergoing percutaneous balloon valvoplasty at a
      tertiary centre between December 1984 and August 1996. Those with an associated
      haemodynamically insignificant atrial septal defect or patent oval foramen were
      also included. Their medical records, echocardiograms and angiograms were
      studied. Colour flow Doppler was used as a semi-quantitative way of assessing the
      pulmonary incompetence. RESULTS: Over the period of review, 57 procedures had
      been performed in 49 patients. The median age at the time of the procedure was
      1.08 years, with a range from 0.01 to 13.3 years. The median period of follow-up
      was 5.64 years, with a range from 3.00 to 14.26 years. Immediately following the
      dilation of the pulmonary valve, the peak-to-peak instantaneous systolic pressure
      gradient was significantly reduced. Seven patients required a second dilation of
      the valve. Their median age at the first valvoplasty, at 0.49 year, was
      significantly lower than those who required only one procedure, at a median of
      1.50 years. Following the valvoplasty, mild pulmonary incompetence was noted in
      26 out of 42 patients the day after the procedure, but only 7% had moderate
      incompetence. On follow-up, there was an increase in the number of patients with
      moderate to severe pulmonary incompetence, from 7% to 29%. Those patients in whom
      the procedure was performed at a younger age had more significant pulmonary
      incompetence. Neither the initial gradient across the pulmonary valve, nor the
      size of the balloon used, were related with statistical significance to the
      subsequent development of pulmonary incompetence. CONCLUSIONS: The majority of
      the patients with congenital isolated pulmonary valvar stenosis had only a mild
      increase in the degree of pulmonary incompetence following a single pulmonary
      valvoplasty. Patients who required the procedure early in life were more likely
      to develop significant pulmonary incompetence. The ratio of the size of the
      balloon to the diameter of the valve did not significantly affect the outcome. We
      suggest that those patients who had more severe stenosis because of a more
      abnormal pulmonary valve, and hence required early intervention, were more likely
      to develop greater pulmonary incompetence after the valvoplasty.

PMID- 14694940
TI  - Visualization of morphological details in congenitally malformed hearts: virtual
      three-dimensional reconstruction from magnetic resonance imaging.
AB  - In recent years, three-dimensional imaging has provided new opportunities for
      visualizing congenital cardiac malformations. We present the initial clinical
      experience using a recently implemented system, which employs some of new
      interactive, real-time, techniques. We show how three-dimensional rendering based
      on magnetic resonance imaging can provide detailed spatial information on both
      intrinsic and extrinsic cardiac relations, and hence how a virtual examination
      can potentially provide new means to a better understanding of complex congenital
      cardiac malformations.

PMID- 14694941
TI  - Three-dimensional magnetic resonance imaging of congenital cardiac anomalies.
AB  - We describe a new method of three-dimensional magnetic resonance imaging of the
      heart that has been used to produce high quality diagnostic images in 274
      patients with congenital cardiac disease, ranging in age from 1 day to 66 years.
      Using a steady state free precession gradient echo technique and parallel
      imaging, rapid acquisition of the entire cardiac volume is possible during 8 to
      15 sequential breath-holds, each lasting between 8 and 15 s. We obtained high
      resolution images, with a resolution of 1 mm3, at between 3 and 10 phases of the
      cardiac cycle. While images of diagnostic quality were obtained in all cases, in
      52 patients there was some degradation due to various factors. Children under 8
      years were ventilated, and ventilation was suspended for the breath-holds. For
      patients breathing spontaneously a novel respiratory navigator technique was
      developed, using a navigator echo placed over the right hemidiaphragm. This was
      used successfully in 20 patients, and reduced the misalignment of images obtained
      during different breath-holds. Images were analysed using multi-planar
      reformatting and volume rendering. Image processing took approximately five
      minutes for each study. End-diastolic images were processed for all patients.
      Systolic images were also processed in selected cases. Further improvements in
      parallel imaging should reduce imaging times further, so that it is possible to
      obtain the full volume image in a single breath-hold. This will enable imaging of
      complex anatomy to be obtained using a standard imaging protocol that does not
      require the operator to understand the cardiac malformation, making the magnetic
      resonance imaging of congenital cardiac disease faster and more effective.

PMID- 14694942
TI  - Cardiac-gated multislice computerised tomographic angiography in the preoperative
      evaluation of an infant with tetralogy of Fallot and pulmonary atresia.

PMID- 14694943
TI  - A fatal case of idiopathic restrictive cardiomyopathy.
AB  - We describe the clinical features of idiopathic restrictive cardiomyopathy in a
      female infant. A marked elevation of left ventricular end-diastolic pressure, and
      profoundly abnormal myocardial relaxation, were detected with the use of Doppler
      blood flow echocardiography, coupled with the relatively new technique of Doppler
      tissue echocardiography. There was no clinical evidence of ongoing heart failure,
      but she had signs of myocardial ischaemia, and unfortunately died suddenly at the
      age of 13 months.

PMID- 14694944
TI  - Mitral perforation: a rare cause of congenital mitral regurgitation.
AB  - In a 4-year-old boy with severe mitral regurgitation, cross sectional
      echocardiography combined with Doppler interrogation confirmed the presence of
      isolated perforation of the aortic leaflet of the mitral valve. The perforation
      was closed with a patch of fresh autologous pericardium. Serial echocardiograms
      taken postoperatively showed no regurgitation across the mitral valve.

PMID- 14694945
TI  - Coronary arterial compression treated by stenting after replacement of the mitral
      valve in a child.
AB  - We describe the clinical history of a nine years old girl with Shone's syndrome.
      She underwent balloon angioplasty of the aortic coarctation in infancy, and later
      developed severe sub-aortic stenosis and moderate mitral valvar stenosis. The
      mitral valve was therefore replaced with a mechanical prosthesis, and the sub
      aortic shelf was resected. Immediately after the operation, she developed signs
      of myocardial ischemia. Coronary angiography showed compression of the middle
      part of the circumflex artery by the mechanical prosthesis, the obstructed
      segment being successfully dilated using a coronary arterial stent.

PMID- 14694946
TI  - A simple method of treating seromas involving modified Blalock-Taussig shunts.
AB  - We treated seromas developing in two patients in relation to left-sided modified
      Blalock-Taussig shunts by reattaching the original graft to the descending aorta.
      We postulate that seromas may develop because of the large area of contact
      between the graft and blood. Shortening the length of the Gore-Tex graft may
      therefore be a feasible treatment.

PMID- 14694947
TI  - Complex congenital cardiac disease in a patient with partial trisomy for the long
      arms of chromosomes 11 and 22.
AB  - Abnormalities of chromosomes 11 and 22 are associated with congenital cardiac
      disease and/or various syndromes. We present a patient with partial trisomy for
      the long arms of chromosomes 11 and 22, the result of a maternal balanced
      reciprocal translocation between these two chromosomes. Our patient was
      dysmorphic and had coarctation of the aorta, an atrioventricular septal defect
      with common atrioventricular junction and exclusively atrial shunting, patency of
      the arterial duct, supracardiac totally anomalous pulmonary venous connection, a
      single kidney, and tracheobronchomalacia. This patient is unusual in having
      extensive left-sided cardiac involvement, a feature not usually found in this
      condition.

PMID- 14694948
TI  - Critical pulmonary stenosis with an aortopulmonary window.
AB  - In neonates with severe aortic or pulmonary stenosis, the obstructed circulation
      is usually supported through patency of the arterial duct. We describe a neonate
      in whom an aortopulmonary window supported a critically obstructed pulmonary
      circulation.

PMID- 14694949
TI  - Manipulating parallel circuits: the perioperative management of patients with
      complex congenital cardiac disease.
AB  - In all patients undergoing cardiac surgery, the effective delivery of oxygen to
      the tissues is of paramount importance. In the patient with relatively normal
      cardiac structures, the pulmonary and systemic circulations are relatively
      independent of each other. In the patient with a functional single ventricle, the
      pulmonary and systemic circulations are dependent on the same pump. As a
      consequence of this interdependency, the haemodynamic changes following complex
      palliative procedures, such as the Norwood operation, can be difficult to
      understand. Comparison of the newly created surgical connections to a simple set
      of direct current electrical circuits may help the practitioner to successfully
      care for the patient. In patients undergoing complex palliations, the pulmonary
      and systemic circulations can be compared to two circuits in parallel.
      Manipulations of variables, such as resistance or flow, in one circuit, can
      profoundly affect the performance of the other circuit. A large pulmonary flow
      might result in a large increase in the saturation of haemoglobin with oxygen
      returning to the heart via the pulmonary veins at the expense of a decreased
      systemic flow. Accurate balancing of these parallel circulations requires an
      appreciation of all interventions that can affect individual components of both
      circulations.

PMID- 14694950
TI  - The prognostic value of balloon occlusion in candidates for the various types of
      cavo-pulmonary anastomosis.
AB  - The purpose of our paper is to assess the prognostic value of balloon occlusion
      as a test for patients with various types of functionally single ventricle after
      different palliative surgical procedures who were candidates for further
      modifications of a cavo-pulmonary operation. In all patients, there were at least
      two sources of pulmonary arterial supply. Our hypothesis was that, using balloon
      occlusion temporarily to produce changes in the haemodynamic situation, we could
      simulate the potential state subsequent to surgical palliation. We used balloon
      occlusion in 19 patients during diagnostic catheterisation, followed by
      interventional and or surgical procedures as considered necessary. This test was
      applied for temporary closure of the pulmonary valve in 8 patients, and a Blalock
      Taussig anastomosis in 11 patients.

PMID- 14694951
TI  - Surgical management of congenital cardiac defects in neonates and young infants
      born with extremely low weight.
AB  - Surgical treatment of cardiac defects in infants born with extremely low weight
      is sometimes required during the neonatal period. Optimal timing of these
      operations has yet to be clarified. With this in mind, we reviewed our experience
      of surgical treatment for 29 infants born with extremely low weight between 1994
      and 2001. The main surgical procedures were ligation of a patent arterial duct in
      26, a Brock procedure in 2, and ligation of an aorto-pulmonary window in 1
      infant. The age at operation ranged from 5 to 57 days, with a median of 30 days,
      and weighed from 506 to 902 g, with a median of 710 g. There were no deaths. For
      the 2 infants undergoing the Brock procedure, the reduced systemic blood flow
      also necessitated closure of the arterial duct. For almost all the 26 infants
      with a patent arterial duct, indomethacin was given as the initial therapy, but
      the duct had not closed completely. Increased symptomatology just before the
      operation due to reduced systemic blood flow, such as decreased cerebral blood
      flow, decreased urine output, and intestinal ischemia, mandated the earlier
      surgical ligation (r = -0.576, p = 0.004). The youngest infant needed an infusion
      of catecholamines perioperatively to maintain stable hemodynamic conditions (r =
      0.554, p = 0.003). In 4 infants, including the youngest 2, steroids were
      administered intravenously just after the ligation. Our results suggest that
      reduced systemic blood flow is the main indication of surgical repair in infants
      born with extremely low weight. Even for one in whom the supply of pulmonary
      blood is dependent on the arterial duct, early reconstruction of the pulmonary
      arterial pathways, using the Brock procedure, followed by ligation of the duct,
      is required. Acute adrenal insufficiency should not be overlooked just after the
      surgery, particularly in the youngest patients.

PMID- 14694952
TI  - Modulation of neurohormonal activity after treatment of children in heart failure
      with carvedilol.
AB  - BACKGROUND: In adults with heart failure, neurohormonal overstimulation is
      related to the progression of the disease, and influences prognosis. beta
      blockers, which modulate neurohormonal activation, now play an essential role in
      the pharmacological management of heart failure in adults, but their use in
      children is very limited. PATIENTS AND METHODS: To investigate the effects of
      carvedilol administration on neurohormonal activation and left ventricular
      function, carvedilol was added to standard treatment for heart failure in 9
      patients with dilated cardiomyopathy due to heart muscle disease. Standard
      treatment has been in place for at least 1 month. The protocol consisted in a
      baseline evaluation to assess neurohormonal activation, and echocardiographic
      evaluation of left ventricular function. This was followed by a final evaluation
      at 12 months from carvedilol loading. Carvedilol was started at 0.05 mg/kg/day,
      and increased every two weeks until the target dose of 0.8 mg/kg/day was reached.
      RESULTS: Carvedilol administration was associated with a significant reduction in
      plasma norepinephrine (p = 0.00001), dopamine (p = 0.0001), aldosterone (p =
      0.00001) and activation of the renin-angiotensin system (p = 0.0006). Similar
      reductions in vanilmandelic and homovanillic acid were noted. After 12 months, a
      positive remodeling took place, with significant reductions in end-diastolic (p =
      0.004) and end-systolic diameters (p = 0.009), and an increase in left
      ventricular ejection fraction (p = 0.001). No adverse effects needing reduction
      or interruption in the dosage were noted in the run-in phase, nor in the period
      of maintenance. CONCLUSION: Carvedilol is a safe complement to standard therapy
      for heart failure in children, allowing a significant reduction of neurohormonal
      activation with evident benefits on both ventricular function and the clinical
      condition.

PMID- 14694953
TI  - Surgery for mitral valvar disease in childhood: should we choose reconstruction
      or repair?
AB  - OBJECTIVE: Modern surgical techniques now offer the potential for reconstructing
      rather than replacing the mitral valve in those patients who require an operation
      during childhood. The purpose of this study was to assess the outcome in our
      centre following mitral valvar surgery in children. METHODS: Between 1992 and
      2002, 51 consecutive children, with a mean age of 12.5 +/- 3.5 years, underwent
      surgical treatment of mitral valvar stenosis and/or insufficiency in the
      Cardiovascular Surgical Department of Istanbul University. Of the children, 20
      underwent repair, whilst we replaced the valve in 31 patients. In one, we
      inserted a pulmonary valvar autograft in mitral position. RESULTS: There were
      neither early nor late deaths in those who underwent mitral valvar repair.
      Similarly, there were no early deaths in those in whom the valve was replaced,
      but two patients died late, while six outgrew their prosthetic valves and
      required insertion of a further valve within 10 years of their first operations.
      CONCLUSION: Our experience shows that procedures designed to repair the mitral
      valve are effective and reliable when performed in children, with low mortality,
      and a lower incidence of reoperation when compared with those having replacement
      of the mitral valve.

PMID- 14694954
TI  - Aortic dissection in children and young adults: diagnosis, patients at risk, and
      outcomes.
AB  - OBJECTIVE: To heighten the awareness of pediatricians and pediatric cardiologists
      to aortic dissection, a potentially dangerous medical condition. METHODS: We
      reviewed the charts of 13 patients, seen in four medical centers, who suffered
      acute or chronic aortic dissection over the period 1970 through 2000 whilst under
      the age of 25 years. RESULTS: There were seven male and six female patients, with
      the mean age at diagnosis being 12.1 years, with a range from one day to 25
      years. Congenital cardiac defects were present in five patients, and Marfan
      syndrome in four. In three of the patients with congenital cardiac defects,
      aortic dissection developed as a complication of medical procedures. In three
      patients, dissection followed blunt trauma to the chest. We could not identify
      any risk factors in one patient. The presenting symptoms included chest pain in
      four patients, abdominal pain and signs of ischemic bowel in two, non-palpable
      femoral pulses in one, and obstruction of the superior caval vein in one.
      Angiography and magnetic resonance imaging were the main diagnostic tools.
      Overall mortality was 38%. Only six patients had successful surgical outcomes.
      CONCLUSION: Due to the rarity of aortic dissection a high index of suspicion is
      required to reach the diagnosis in a timely manner. It should be considered in
      young patients complaining of chest pain in association with Marfan syndrome,
      anomalies of the aortic valve and arch, and chest trauma.

PMID- 14694955
TI  - Cardiomyopathy in congenital disorders of glycosylation.
AB  - Congenital disorders of glycosylation are a group of inherited metabolic
      multisystem disorders characterized by defects in the glycosylation of proteins
      and lipids. In most cases, neuromuscular disease is present. The purpose of this
      study was to characterize the cardiological aspects in this disorder. From the
      literature, we identified six children with congenital disorders of glycosylation
      associated with cardiac disease. We then screened for cardiovascular
      manifestations 20 patients diagnosed with congenital disorders of glycosylation
      at our own institution. Of the 6 patients identified in the literature, 4 had
      hypertrophic cardiomyopathy, while in the other 2 the cardiac diagnosis was
      unclear. The mean age at cardiac diagnosis was 5 months, with a range from 34
      weeks to 24 months. Of the patients, five had died at a mean age of 3.5 months,
      with a range from 1.5 to 6 months, with one documented cardiac death. Three of
      our 20 patients (15%) had coexistent cardiomyopathy, and in three additional
      patients presenting with cardiomyopathy we made the diagnosis of a congenital
      disorder of glycosylation. In our cohort, dilated cardiomyopathy was found in two
      thirds of the patients, with hypertrophic cardiomyopathy in the other third. The
      mean age at cardiac diagnosis was 19 months, with a range from 0.5 to 84 months.
      Of these patients, two died in infancy at a mean age of 4 months, specifically at
      1.5 and 7 months, due to cardiac disease, with one dying suddenly. The remaining
      four patients are alive with minor to severe cardiac dysfunction. We conclude
      that congenital disorders of glycosylation have to be considered in the
      differential diagnosis of children presenting with cardiomyopathy, and that all
      patients with congenital disorders of glycosylation should be screened for an
      associated cardiomyopathy. Cardiac involvement contributes significantly to
      morbidity and mortality, and probably to sudden cardiac death in this disorder.

PMID- 14694956
TI  - Predictors of residual defects following closure of defects in the oval fossa
      using the Amplatzer device: echocardiography recapitulates morphometry.
AB  - OBJECTIVES: This study was designed to identify predictors of residual defects
      following deployment of the Amplatzer device to close septal defects within the
      oval fossa. METHODS: Between February 1997 and February 2000, we used the
      Amplatzer device to close defects in the oval fossa in 89 patients. Of these
      patients, 18 (20%) had residual defects. At 6 or 12 months following placement of
      the device, 13 defects (14.6%) had persisted. We evaluated several variables
      derived from clinical features, transesophageal echocardiography and
      catheterization to establish predictors for residual shunting. RESULTS:
      Multivariate analysis identified a shorter superior rim of less than 8 mm (Odds
      ratio = 10.1; 95% confidence intervals = 2.64-38.72; p = 0.001), and a smaller
      interatrial septum in the 30-degree transesophageal echocardiographic plane of
      less than 30 mm (Odds ratio = 5.5; 95% confidence intervals = 1.17-26.14; p =
      0.03) as independent predictors of residual defects. When the analysis was
      repeated defining only those 13 patients with persisting residual defects at 6 or
      12 months as failures, a short superior rim (p = 0.004) remained a predictor for
      residual shunting. CONCLUSIONS: Defects with a short superior rim and smaller
      interatrial septum in the 30-degree transesophageal echocardiographic plane
      independently and additively predict an increased probability of residual
      shunting following closure of defects in the oval fossa using the Amplatzer
      device.

PMID- 14694957
TI  - Iloprost in persistent pulmonary hypertension of the newborn.
AB  - Aerosolized iloprost is now used as a therapeutic option in the treatment of
      pulmonary hypertension. We report on the administration of this derivative of
      prostacycline in treating severe pulmonary hypertension of the newborn. The
      combination of iloprost instilled endotracheally and inhaled was chosen as a last
      attempt at treatment in a critically ill patient who did not respond to advanced
      conventional treatments, including high frequency oscillation and inhalation of
      nitric oxide. The use of iloprost converted permanently the right-to-left
      shunting, leading to a substantial improvement in oxygenation.

PMID- 14694958
TI  - Severe pulmonary hypertension secondary to a parachute-like mitral valve, with
      the left superior caval vein draining into the coronary sinus, in a girl with
      Turner's syndrome.
AB  - A 17-year-old girl with Turner's syndrome underwent two cardiac operations due to
      severe mitral stenosis with pulmonary hypertension, caused by a parachute-like
      mitral valve. The anomaly was associated with persistence of the left superior
      caval vein, which drained to the coronary sinus, and non-compaction of the left
      ventricular myocardium. The association of these lesions is rare in patients with
      Turner's syndrome.

PMID- 14694959
TI  - Exercise-induced left bundle branch block in a young female athlete.
AB  - An 11-year-old female, in apparent good health, was referred to our Institute
      because of exercise-induced left bundle branch block detected during a Master's
      step test performed to obtain the clearance for competitive sport. The tests that
      we performed to investigate the possible causes were all negative. We suspect,
      however, that the left bundle branch block is the initial sign of cardiomyopathy.
      If our suspicions are correct, close follow-up is important to chart the possible
      progression of the disease.

PMID- 14694960
TI  - Ebstein's malformation in the setting of Down's syndrome.
AB  - We report a patient with Down's syndrome referred to our Department of
      Echocardiography for evaluation after an episode of tachyarrhythmia. We diagnosed
      Ebstein's malformation. As far as we know, this association has been reported
      previously on only three occasions. We review these previous cases, describe our
      echocardiographic techniques, and discuss our experience.

PMID- 14694961
TI  - Reversible cardiomyopathy subsequent to perinatal infection with the human
      immunodeficiency virus.
AB  - We describe a patient with advanced perinatal acquired immunodeficiency syndrome
      who had early clinical manifestation of severe dilated cardiomyopathy with
      congestive heart failure. The picture was completely reversed after six years
      treatment and follow-up, and the child is now doing well at the age of seven,
      with normal left ventricular dimension and contractility as shown by
      echodopplercardiography. To the best of our knowledge, this is the first reported
      case of full recovery from cardiomyopathy in children with perinatally acquired
      infection by the human immunodeficiency virus.

PMID- 14694962
TI  - Coronary stenting for a muscular bridge in a patient with hypertrophic
      obstructive cardiomyopathy.
AB  - A young woman with hypertrophic cardiomyopathy presented with intractable chest
      pain due to a myocardial bridge over the left anterior descending artery,
      producing severe compression during systole. Percutaneous intracoronary stenting
      was performed. The patient, however, developed severe and diffuse restenosis
      within 30 days of the procedure. Myotomy may provide a more effective treatment
      option for such patients with symptomatic myocardial bridging.

PMID- 14694963
TI  - Successful management of fetal hydrops due to congenitally complete
      atrioventricular block.
AB  - At 32 weeks, a fetus was found to be hydropic with congenitally complete heart
      block in an asymptomatic mother who was positive to anti-Ro antibodies. Maternal
      therapy with oral salbutamol was successful in prolonging gestation for a period
      of 3 weeks so that preterm delivery was delayed until the 35th week of gestation.
      Following treatment with inotropes and diuretics, a permanent transvenous
      pacemaker was implanted at 8 weeks of age. The child is now thriving at 20 months
      of age.

PMID- 14694964
TI  - Transient severe isolated right ventricular hypertrophy in neonates.
AB  - We report two instances of transient isolated right-sided myocardial hypertrophy
      in patients with an intact ventricular septum, normal thickness of the posterior
      wall of the left ventricle, and normal ventricular function, diagnosed by
      echocardiography on the third day of life. The two neonates, born at 36 and 38
      weeks gestation respectively, had perinatal distress. Both were diagnosed as
      having isolated right ventricular hypertrophy with mild pulmonary hypertension,
      which disappeared in both cases within 8 weeks without any specific therapy.
      Though the cause of the ventricular hypertrophy remains unclear, we believe that
      it is the consequence of remodeling of pulmonary vasculature secondary to acute
      perinatal distress, resulting in persistent pulmonary hypertension and producing
      pressure overload on the right ventricle, and hence right ventricular
      hypertrophy. The finding of early and transient right ventricular hypertrophy,
      with normal left-sided structures and normal ventricular function, has thus far
      failed to gain attention in the paediatric cardiologic literature.

PMID- 14694965
TI  - Forty years of European Paediatric Cardiology.

PMID- 14694966
TI  - Intrahepatic right-to-left shunting after the Fontan operation.

PMID- 14694967
TI  - Surfactant therapy is still on the move.

PMID- 14694968
TI  - Placental transfer of tetanus-specific immunoglobulin G in Iranian mothers.
AB  - OBJECTIVES: To investigate placental transfer of anti-tetanus immunoglobulin
      (Ig)G antibodies in Iranian mothers. METHODS: Sera collected from 209 pregnant
      women and their paired infants were evaluated for tetanus-specific antibodies by
      a commercial enzyme-linked immunosorbent assay. RESULTS: In total, 15 (7.2%) out
      of 209 mothers and 12 (5.7%) out of 209 newborns were negative for anti-tetanus
      IgG. A highly significant correlation was observed between maternal and fetal
      anti-tetanus IgG (r = 0.80). The mean cord/maternal blood ratio of anti-tetanus
      IgG was 1.22 +/- 0.97. The mean cord/maternal blood ratio of anti-tetanus IgG in
      mothers with blood groups B+ and AB+ was lower than in mothers with other blood
      groups (p = 0.027). In addition, among mothers who had more than 0.5 IU/ml anti
      tetanus IgG, a higher percentage of cases with cord/maternal blood ratio of < 1
      was observed in carriers of blood groups B+ and AB+ compared to those with other
      blood groups (45.2% vs. 41.8%). Parity of more than 4 had a significant negative
      effect on both frequency of high positive sera and the mean of anti-tetanus IgG
      level in maternal and neonatal sera. CONCLUSIONS: A relatively high percentage of
      pregnant women were not immune against tetanus. It was also found that the main
      factors that affect infants' tetanus-specific IgG are maternal concentration of
      this immunoglobulin, parity and maternal blood group.

PMID- 14694969
TI  - Maternal and fetal inflammatory responses in unexplained fetal death.
AB  - OBJECTIVE: The role of intra-amniotic infection in the etiology of fetal death
      has been proposed. This study was conducted to determine the prevalence of
      microbial invasion of the amniotic cavity (MIAC) and the frequency of maternal
      and/or fetal inflammation in patients presenting with a fetal death. METHODS: A
      prospective study was conducted in patients with a fetal death. Amniocenteses
      were performed for clinical indications (karyotype), as well as to assess the
      microbiological and cytological state of the amniotic cavity. Fluid was cultured
      for aerobic and anaerobic bacteria and genital mycoplasmas. An amniotic fluid
      white blood cell count and glucose determinations were also performed.
      Histological examination of the placenta was conducted to identify a maternal
      inflammatory response (acute chorioamnionitis) or a fetal inflammatory response
      (funisitis). RESULTS: This study included 44 patients with intrauterine fetal
      death. The median gestational age at diagnosis was 30.1 weeks (range 16.3-40.4
      weeks). One patient had documented MIAC (1/44). Acute histological
      chorioamnionitis was found in 20.9% (9/43), but a fetal inflammatory response was
      observed in only 2.3% (1/43) of cases. One patient had a positive amniotic fluid
      culture for Streptococcus agalactiae (group B streptococcus). CONCLUSION:
      Histological chorioamnionitis was present in 20.9% of cases, but MIAC could be
      demonstrated with conventional microbiological techniques in only one case. A
      fetal inflammatory response was nine times less frequent than a maternal
      inflammatory response (maternal 20.9% vs. fetal 2.3%, p = 0.008) in cases of
      fetal death.

PMID- 14694970
TI  - Cervical ripening and induction of labor by prostaglandin E2: a comparison
      between intracervical gel and vaginal pessary.
AB  - OBJECTIVE: To compare the effectiveness and safety of two formulations of
      prostaglandin (PG) E2 (gel and pessary) for induction of labor. Primary outcomes
      were cervical ripening, initiation/duration of labor, and type of delivery. STUDY
      DESIGN: A total of 115 women with singleton gestations were consecutively
      enrolled and assigned to receive intracervical PGE2 (dinoprostone 0.5 mg) by gel
      (n = 66) or PGE2 (dinoprostone 10 mg) by intravaginal pessary (n = 49). RESULTS:
      Independently from parity, the vaginal pessary induced successful cervical
      ripening with a slightly higher but not statistically significant occurrence of
      vaginal delivery with respect to gel induction. The mean time interval from
      induction to vaginal delivery did not differ between groups, despite being
      shorter for the pessary group in inducation-delivery intervals > 12 h. No
      significant differences were found between the groups with respect to patients
      who required a second course of PGE2 (9% vs. 2%), as well as oxytocin (11% vs.
      13%) induction. No significant difference was found in the incidence of uterine
      hyperstimulation and other adverse reactions in nulliparas, or in fetal and
      neonatal outcome. CONCLUSION: Independently from parity, both PGE2 administration
      routes appeared to be effective in achieving cervical ripening, initiation of
      labor and optimal type of delivery, and showed the same incidence of side
      effects.

PMID- 14694971
TI  - Effectiveness and safety of a structured swimming program in previously sedentary
      women during pregnancy.
AB  - OBJECTIVE: To determine whether undertaking a swimming program in sedentary women
      during pregnancy would improve maternal fitness without adverse fetal
      consequences. METHODS: Prospective observational investigation of healthy
      sedentary pregnant women participating in a monitored swimming program. RESULTS:
      Twenty-three women attended swimming sessions from 16 to 28 weeks of gestation
      resulting in increasing distances swum and improved aerobic fitness as measured
      by physical work capacity (PWC170) (p = 0.003). Resting maternal heart rate
      decreased (p = 0.041) and resting systolic (p = 0.092) and diastolic (p = 0.971)
      blood pressures remained unchanged over gestation. The mean fetal heart rates
      decreased with advancing gestational age (p = 0.001), consistent with normal
      physiology. Non-stress tests and umbilical artery systolic/diastolic ratios were
      similar before and after swimming sessions, providing evidence that fetal well
      being was unchanged. CONCLUSIONS: A structured swimming program in sedentary
      pregnant women increases maternal fitness without any alteration in maternal and
      fetal well-being.

PMID- 14694972
TI  - Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in
      plasma/serum and urine of women during term and threatened preterm labor: a
      clinical approach.
AB  - OBJECTIVE: To explore the concentrations of matrix metalloproteinase-9 (MMP-9)
      and tissue inhibitor of metalloproteinase-1 (TIMP-1) in plasma, serum and urine
      of women during term and threatened preterm labor. METHODS: Plasma and urine
      proMMP-9 as well as serum and urine TIMP-1 were evaluated in 60 healthy pregnant
      women; 20 of them presented in term labor following an uncomplicated pregnancy,
      20 of them presented with threatened preterm labor and intact membranes at 24-36
      gestational weeks and 20 of them were at 24-40 gestational weeks with no evidence
      of uterine contractions or other pregnancy complications. Data were analyzed with
      non-parametric statistical tests and cut-off values were determined with receiver
      operator characteristic curves. RESULTS: ProMMP-9 values were significantly
      higher and TIMP-1 values were significantly lower in cases with uterine term or
      preterm contractions compared to non-labor status; and in cases with preterm
      contractions that progressed to true preterm labor compared to those in which
      contractions were arrested. CONCLUSIONS: Alterations in the concentrations of
      proMMP-9 and TIMP-1 can be detected in plasma or serum and urine of pregnant
      women experiencing term or preterm uterine contractions. The altered values of
      proMMP-9 and TIMP-1 could possibly identify the inevitable progress of preterm
      contractions to true preterm labor.

PMID- 14694973
TI  - Follow-up of unilateral multicystic kidney dysplasia after prenatal diagnosis.
AB  - OBJECTIVES: Since the introduction of antenatal diagnostic screening, multicystic
      kidney dysplasia (MCKD) has been diagnosed in 1 of 4300 live births. We analyze
      our own experience and demonstrate a management regime based on these results and
      existing studies. METHODS: Retrospective data analysis was carried out in 110
      patients, prenatally diagnosed with MCDK. A total of 93 patients with confirmed
      diagnosis of unilateral MCDK were born alive and followed up in our institutions.
      RESULTS: A total of 110 unilateral cystic kidneys were prenatally diagnosed; 93
      were confirmed postnatally. These children were retrospectively allocated to two
      treatment groups: 51 were operated upon; 42 were treated conservatively. A
      micturition cystourethrogram was performed 88 times, yielding 20 pathological
      findings. Vesicoureteral reflux was identified 11 times (12.5%). Eleven children
      (12%) had associated non-urological abnormalities. Cardiac and musculoskeletal
      malformations predominated. After 1995, nephrectomy was performed only when
      clinically indicated. Thirty-seven children were treated conservatively for
      between 4 months and 6 years (mean 33 months); 28 dysplastic kidneys exhibited
      size reduction. Complete involution was noted in 16 of 28 children between 7 and
      29 months (mean 16.2 months). CONCLUSION: This study provides evidence that
      neonatal nephrectomy of unilateral MCDK is rarely required. It also shows that
      the discussed malformation is not an isolated developmental abnormality. In a
      high proportion, associated urogenital abnormalities were present and
      therapeutically relevant, and determined the overall prognosis.

PMID- 14694974
TI  - Clinical course of premature infants intubated in the delivery room, submitted or
      not to porcine-derived lung surfactant therapy within the first hour of life.
AB  - OBJECTIVES: The aim of this study was to perform a comparative analysis of the
      clinical outcome, gasometric course and ventilatory indices of premature infants
      with a gestational age of < or = 34 weeks who were intubated in the delivery
      room, owing to respiratory insufficiency, according to whether or not they were
      submitted to porcine-derived lung surfactant therapy within the first hour of
      life. METHODS: The study was randomized and controlled. A total of 75 premature
      infants were classified into two groups: group A, comprising 35 neonates who were
      submitted to surfactant within the first hour of life; and group B, comprising 40
      neonates who were not submitted to surfactant within the first hour of life.
      RESULTS: Exogenous surfactant therapy after establishment of respiratory distress
      syndrome (RDS) was necessary in eight neonates of group A (22.9%) and 31 neonates
      of group B (77.5%) (p < 0.001). The neonates in group A presented higher levels
      in relation to group B for the variables: partial pressure of arterial oxygen
      (PaO2)/fraction of inspired oxygen (FiO2) and PaO2/partial pressure of alveolar
      oxygen (PAO2), while neonates in group B presented higher levels for FiO2, PAO2
      and difference D(A - a)O2 in relation to group A. Weight affected the oxygenation
      index (OI) parameter, in that neonates with lower weight presented greater values
      of the OI. CONCLUSIONS: In premature infants with established RDS, the need for
      exogenous surfactant was lower in the group that received surfactant within the
      first hour of life. Furthermore, the gasometric parameters and ventilatory
      indexes presented a better course in the first 24 h of life among premature
      infants who received exogenous surfactant within the first hour of life, in
      relation to those who did not.

PMID- 14694975
TI  - An observational study of surfactant treatment in infants of 23-30 weeks'
      gestation: comparison of prophylaxis and early rescue.
AB  - OBJECTIVE: To test the clinical efficacy of exogenous surfactant for treatment of
      neonatal respiratory distress syndrome (RDS). METHODS: In a retrospective
      multicenter observational study, data were collected on 987 infants of 23-30
      weeks' gestation given surfactant for respiratory problems within 3 h of birth.
      Obstetric, neonatal and short-term outcome data were retrieved from recording
      charts and analyzed after subdivision of the sample into two treatment groups:
      prophylaxis (surfactant within 15 min) and early rescue (surfactant at 16-180
      min). RESULTS: A total of 965 infants were eligible for the study: 244 receiving
      prophylaxis and 721 receiving early rescue. The prophylaxis group had lower
      gestational ages and birth weights than the early rescue group (p = 0.0001), but
      were otherwise comparable. Natural surfactants were used in > 90% of infants in
      both groups. The rates of retreatments and the mean total doses of surfactant
      were similar in both groups. Babies receiving prophylaxis presented less grade 3
      4 RDS than those receiving early rescue (32.4% vs. 53.8%, p = 0.0001). Those
      requiring prophylaxis also needed lower peak inspiratory pressure and had a
      shorter duration of oxygen therapy. Mortality and complications were similar
      between the groups, but babies receiving prophylaxis had less pulmonary
      interstitial emphysema (p = 0.0006) and periventricular leukomalacia (p = 0.0113)
      than infants receiving early rescue. CONCLUSIONS: In clinical practice,
      prophylaxis was preferred in babies with lower birth weights and gestational ages
      compared to early rescue treatment. Not surprisingly, infants treated with
      prophylactic surfactant had a lower rate of RDS than the infants treated by early
      rescue, even though they did not need less surfactant overall.

PMID- 14694976
TI  - Interleukin-1beta in the bronchoalveolar lavage fluid of premature neonates: a
      marker for maternal chorioamnionitis and predictor of adverse neonatal outcome.
AB  - OBJECTIVE: To determine whether the presence of the proinflammatory cytokine
      interleukin (IL)-1beta in the lungs of preterm infants immediately after birth
      was associated with maternal inflammation and could predict adverse neonatal
      outcome. STUDY DESIGN: Prospective evaluation of serially obtained tracheal
      aspirates for the presence of IL-1beta in 25 preterm infants (birth weight 595
      1700 g; gestational age 24-32 weeks) with respiratory distress syndrome. The
      initial tracheal aspirate was obtained within 1 h after delivery. RESULTS: An
      initial tracheal aspirate positive for IL-1beta had a highly significant
      correlation with documented maternal chorioamnionitis for the given patient. In
      addition, the presence of IL-1beta correlated significantly with elevated total
      cell count (2.62 vs. 0.96 x 10(6)/ml, p = 0.0097), granulocyte count (2.12 vs.
      0.22 x 10(6)/ml, p = 0.001), macrophage count (0.28 vs. 0.01 x 10(6)/ml, p =
      0.02) and the presence of proinflammatory cytokines IL-6, IL-8 and tumor necrosis
      factor (TNF)-alpha. Preterm neonates positive for IL-1beta in their initial
      sample were on prolonged assisted ventilation (38 vs. 16 days, p = 0.013) and
      oxygen supplementation (62 vs. 40.5 days, p = 0.0462) and required prolonged
      hospitalization (69 vs. 46 days, p = 0.0165). CONCLUSIONS: The concentration of
      IL-1beta in the initial tracheal aspirate obtained from the lungs of preterm
      infants within the first hour of life may serve as a marker of
      antenatal/perinatal inflammation, probably due to maternal chorioamnionitis, and
      could predict an adverse clinical course and short-term outcome.

PMID- 14694977
TI  - First reported use of caspofungin in an extremely low-birth-weight neonate.

PMID- 14694978
TI  - Pigmented lesions in unusual anatomic sites.
AB  - This review considers pigmented melanin-containing lesions arising in
      extracutaneous locations. It includes reactive lesions as well as benign and
      malignant neoplasms. Melanocytic lesions of the mucosae, nervous system, and
      individual organs are discussed, and rarer pigmented tumors in unusual sites are
      also covered. A brief description of the histology and clinical behavior along
      with proposed explanations for their ectopic location are provided. Emphasis is
      given to the reality that detailed morphological evaluation and application of
      ancillary techniques can establish the melanocytic nature and biologic potential
      of such tumors, but cannot, by themselves, determine the primary or metastatic
      nature of these lesions.

PMID- 14694979
TI  - Germ cell tumor-like neoplasms occurring outside the anatomic midline.
AB  - Most germ cell tumors occur in the gonads or in extragonadal sites in the
      anatomic midline; this article reviews tumors with similar or identical
      histologic features that arise in other topographic locations. Such lesions often
      represent the presence of "germ cell-like" or "germinal" components in what is
      otherwise recognized as a somatic neoplasm; however, they may also occur in pure
      form. The morphologic and immunohistochemical features of these proliferations
      are reviewed, according to the types of germ cell tumors that they recapitulate.

PMID- 14694980
TI  - Paratesticular mesothelial proliferations.
AB  - Varied mesothelial proliferations are found around the testes. Benign reactive
      mesothelial proliferations in hydrocoeles may be very florid and histologically
      worrisome, but these can usually be separated from malignant mesotheliomas of the
      tunica vaginalis because they are confined to a sharply demarcated zone near the
      luminal surface. In addition, benign inflamed hydrocoeles tend to show a distinct
      zonation with cellular areas near the luminal surface and more fibrotic areas
      beneath. The proliferating mesothelial cells in benign reactions often form lines
      that are parallel to the surface of the hydrocoele. Malignant mesotheliomas of
      the tunica vaginalis are usually grossly visible as single or multiple nodules.
      Histologically, they show an epithelial- or mixed epithelial- and sarcomatous
      morphologic image, with evidence of stromal invasion. Well-differentiated
      papillary mesotheliomas are usually solitary exophytic nodules with a distinctive
      morphologic appearance and benign course, but they must be carefully separated
      from malignant mesotheliomas with a focally exophytic papillary growth pattern.
      By definition, well-differentiated papillary mesotheliomas do not exhibit stromal
      invasion. Peritesticular adenomatoid tumors are also very common; they are benign
      circumscribed cellular nodules with an appearance comparable to that of
      adenomatoid tumors in other body locations such as the uterine serosa.

PMID- 14694981
TI  - Salivary-type neoplasms of the breast and lung.
AB  - Salivary-type tumors occur in multiple sites in the human body, likely related to
      a basic structural homology between exocrine glands in these different anatomic
      areas. This paper reviews these salivary gland tumor types in breast tissue and
      lung. Salivary-type tumors of both breast and lung are relatively uncommon in
      comparison to their salivary gland counterparts. This may be attributable in part
      to lack of familiarity with these tumors in extra-salivary sites, and in part to
      histologic overlap with other primary and metastatic tumor types. Recognition of
      these entities is improving as the clinical and pathologic features are better
      delineated, and tumors are more accurately classified. Prediction of malignant
      behavior is not always possible in these unusual sites. In some instances, such
      as adenoid cystic carcinoma, behavior is known to differ considerably from that
      of analogous primary salivary gland tumors and in other instances there are
      simply too few reported cases to allow for adequate prognostication. In fact,
      more recent papers discuss the need to consider a spectrum encompassing benign
      and malignant lesions, in both breast and lung. Of course, some entities show
      clear-cut evidence of malignancy with documented potential for metastasis, others
      show bland features and well-reported benign behavior, and the less well-defined
      entities reside between these two extremes. The molecular pathology of salivary
      gland tumors has been reasonably well investigated in that location; however;
      there are few molecular studies devoted to salivary-type tumors of the breast and
      lung. This represents a potential area for future growth in further clarifying
      these tumors and their behavior.

PMID- 14694982
TI  - Ectopic neural and neuroendocrine neoplasms.
AB  - Although neural and neuroendocrine tissues are distributed virtually ubiquitously
      throughout the body, the occurrence of selected neoplasms related to those
      lineages is extremely uncommon in some topographic sites. This review considers
      the clinicopathologic characteristics of heterotopic pituitary adenomas;
      neuroendocrine carcinomas in non-organ-based locations; ectopic (extraneuraxial)
      meningiomas and gliomas; visceral neuroblastic neoplasms and primitive
      neuroectodermal tumors; and paragangliomas arising outside the sympathoadrenal
      neural network. Practical approaches to differential diagnosis are emphasized.

PMID- 14694983
TI  - Pediatric-type sarcomas in adult patients.
AB  - Sarcomas included in the broad group of small round-cell tumors (SRCT) and some
      non-SRCT lesions that typically are seen in pediatric-age patients can rarely
      occur in adults. However, there are differences in the anatomic sites that are
      involved and the prognosis in these two patient groups. The diagnosis of
      pediatric-type sarcomas in adults is often challenging because of the unusual
      contextual clinical setting and morphologic features. Immunohistochemical studies
      have greatly facilitated this process. Moreover, limited biomolecular studies
      that have been conducted have demonstrated comparable cytogenetic alterations in
      adults and children with pediatric-type tumors. They also have raised interesting
      questions concerning possible biological bases for differences in clinical
      behavior in the two cohorts. This review focuses on the morphological,
      immunohistochemical, and molecular characteristics of childhood-type sarcomas
      that affect adults, with emphasis on possible pitfalls in differential diagnosis.

PMID- 14694984
TI  - Extramedullary hematopoietic proliferations, extraosseous plasmacytomas, and
      ectopic splenic implants (splenosis).
AB  - Hematopoietic proliferations are well known to present ectopically outside the
      bone marrow, either in benign or malignant form. As such, they present a distinct
      problem with respect to morphologic interpretation because of their uncommonality
      in extramedullary sites and their capacity to simulate other lesions
      histologically. This review considers extramedullary myeloid tumors
      ("granulocytic sarcoma," "erythroblastic sarcoma," "megakaryocytic sarcoma"),
      tumefactive extramedullary hematopoiesis, and the peculiar condition known as
      "splenosis," with consideration of their clinical, microscopic, and
      cytohistochemical chararacteristics.

PMID- 14694985
TI  - Peptide inhibitors of hepatitis C virus NS3 protease.
AB  - Hepatitis C virus (HCV) is a highly prevalent virus and one of the major agents
      of chronic hepatitis. Since HCV NS3 protease is essential for the processing of
      HCV polyprotein, this protease is a target of choice to control HCV replication.
      Peptide inhibitors of NS3 were developed by selective amino acid replacement of
      six leader sequences, corresponding to regions of HCV polyprotein that are
      cleaved by NS3. The large numbers of potential 14-mer and 16-mer peptide
      inhibitors thus obtained were tested against NS3 using the fluorescent probe
      RETS1 and peptide cofactor SVVIVGRIILSGRA from NS4A protein. This afforded
      several peptide inhibitors with an IC50 of around 2 microM. These peptides may be
      good leading compounds for the development of peptidomimetics to control HCV
      replication in the treatment of chronic hepatitis C.

PMID- 14694986
TI  - In vitro and in vivo activities of T-705 and oseltamivir against influenza virus.
AB  - T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has a potent and selective
      inhibitory activity against influenza virus. We studied the effects of an
      infectious dose on the anti-influenza virus activities of T-705 and oseltamivir,
      a commercially available neuraminidase inhibitor, both in vitro and in vivo.
      Plaque formation of influenza A/PR/8/34 virus was completely inhibited by 10
      microg/ml of T-705 after 72 h incubation, whereas visible plaque formation was
      detected in the plate treated with GS 4071, the active form of oseltamivir (10
      microg/ml). The antiviral activity of T-705 was not influenced by an increase in
      multiplicity of infection (MOI) from 0.0001 to 1, but that of GS 4071 was
      influenced in a yield reduction assay. No increase in viral yield was seen in
      either culture supernatant or cells after removal of T-705 (10 microg/ml) but, in
      contrast, productive infection recurred in culture supernatant and in cells after
      removal of GS 4071. In mice infected with a high challenge dose of influenza
      A/PR/8/34 virus, orally administered T-705 (200 and 400 mg/kg/day) completely
      prevented the death of mice and the survival rates of mice were significantly
      higher than those in mice treated with oseltamivir (P<0.01). When the treatment
      was delayed at 1, 13 and 25 h post infection, oral administration of 200 mg/kg of
      T-705 significantly prevented the death of mice (P<0.01), and the survival rates
      of mice treated with T-705 were comparable to those of mice treated with
      oseltamivir. These results suggest that T-705 has the potential to be a potent
      inhibitor of human influenza virus infections.

PMID- 14694987
TI  - Antiherpes virus activities of new 6-19 carbon-bridged steroids and some
      synthetic precursors.
AB  - Three synthetic 6,19-carbon bridged steroids: 3beta,20beta-diacetyloxy-5alpha
      chloro-19a(R)-hydroxy-6,19-methanopregnane, 3beta,20beta-diacetyloxy-5alpha
      chloro-6,19-methanopregnane, 6,19-methanopregn-4-ene-3,20-dione and four
      synthetic precursors: 3beta,20beta-diacetyloxy-19-hydroxypregn-5-ene,
      3beta,20beta-diacetyloxy-pregn-5-en-19-al, 3beta,20beta-diacetyloxy-19(E)
      (methoxymethylidene)-pregn-5-ene and 20beta-acetyloxy-3beta-hydroxy-19(E)
      (methoxymethylidene)-pregn-5-ene were tested against herpes virus replication in
      cell cultures. Several compounds were cytotoxic for stationary cells. Antiviral
      studies performed with all compounds against HSV-1 indicated a dose-dependent
      virus susceptibility with selectivity indexes (SI) values in the range 1.7-183.2.
      Selected compounds were also tested against HSV-2 and the SI values obtained were
      in the range of 31-273. Attempts to reveal the step of virus multiplication
      affected by pregnanes were performed with one compound. HSV-1 virus incubation
      with the compound did not alter the ability of virus particles to infect cells;
      moreover, neither virus adsorption nor penetration appeared to be affected. The
      drug must be present during at least the first 7 h of the virus cycle to inhibit
      more than 90% of virus production. All these results suggest that these novel
      molecules interfere with an intracellular step of virus multiplication, thus
      behaving like true antivirals.

PMID- 14694988
TI  - Structure-activity relationship studies on a novel family of specific HIV-1
      reverse transcriptase inhibitors.
AB  - We have previously reported the discovery and preliminary structure-activity
      relationships of a new class of specific HIV-1 reverse transcriptase (RT)
      inhibitors whose prototype compound is the 1-[2',5'-bis-O-(tert
      butyldimethylsilyl)-beta-D-ribofuranosyl]-3-N-[(carboxy) methyl]-thymine. In an
      attempt to increase the inhibitory efficacy against HIV-1 RT of this new class of
      nucleosides, and to further explore the structural features required for anti-HIV
      1 activity, different types of modifications have been carried out on the
      prototype compound. These include substitution of the tert-butyldimethylsilyl
      groups by other liphophilic groups, replacement of the carboxy group at the N-3
      position of the nucleobase by other functional groups, change in the length of
      the spacer between the thymine and the carboxylic acid residue and substitution
      of the thymine moiety by other pyrimidine (uracil, 5-ethyluracil) or purine
      (hypoxanthine) nucleobases. In addition, the most salient structural features of
      this new class of HIV-1-specific nucleosides have been incorporated into
      classical HIV RT nucleoside inhibitors such as ddl, AZT, d4T. Our studies
      demonstrate that both the carboxymethyl moiety at the nucleobase and tert
      butyldimethylsilyl groups at the sugar are important structural components since
      deletion of either of them is detrimental to the antiviral activity.

PMID- 14694989
TI  - Pharmacokinetic evaluation of 3'-azido-2', 3'-dideoxyuridine-5'-O-valinate
      hydrochloride as a prodrug of the anti-HIV nucleoside 3'-azido-2', 3'
      dideoxyuridine.
AB  - 3'-Azido-2', 3'-dideoxyuridine (AZDU, AzddU, CS-87) has been shown to have potent
      anti-HIV activity in vitro. However, the compound exhibits a relatively short
      half-life and incomplete oral bioavailability in humans. In an effort to improve
      the pharmacokinetic properties of AZDU, prodrug 3'-azido-2',3'-dideoxyuridine-5'
      O-valinate hydrochloride (AZDU-VAL) was synthesized by the esterification of 5'
      OH function in AZDU. The objective of this study was to investigate the
      biotransformation and pharmacokinetics of AZDU-VAL along with its antiviral
      parent compound AZDU following intravenous and oral administration to rats. Adult
      male Sprague-Dawley rats were administered AZDU or AZDU-VAL by intravenous
      injection or oral gavage. Concentrations of AZDU-VAL and AZDU were determined by
      HPLC. Pharmacokinetic parameters were generated by area-moment analysis. The
      bioavailability of AZDU after oral administration was approximately 53%. The
      terminal phase half-life of the nucleoside analogue ranged between 0.6 h after
      intravenous administration and 1 h following oral administration. In vivo the
      prodrug was rapidly and efficiently biotransformed to yield AZDU following
      intravenous and oral administration. The apparent availability of AZDU was
      virtually complete following oral administration of prodrug AZDU-VAL averaging
      101%. The bioavailability of AZDU following intravenous administration of AZDU
      VAL averaged 106%. In summary, the disposition of AZDU was dose dependent over
      the dose range of 25-100 mg/kg. Renal clearance and steady state volume of
      distribution were lower at the higher dose level. Prodrug AZDU-VAL demonstrated
      improved oral bioavailability as evidenced by complete absorption and efficient
      bioconversion to AZDU. The results suggest that AZDU-VAL may be a promising
      prodrug for the delivery of AZDU.

PMID- 14694990
TI  - Synthesis and antiviral activity of 1,3-disubstituted uracils against HIV-1 and
      HCMV.
AB  - The development of new non-nucleoside reverse transcriptase inhibitors (NNRTIs)
      is an efficient strategy for finding new therapeutic agents against human
      immunodeficiency virus (HIV). A large number of 6-substituted uracil derivatives
      have been prepared in order to explore new NNRTIs. However, there are few
      approaches to anti-HIV agents from 1,3-disubstituted uracil derivatives.
      Therefore, we tried to prepare several 1,3-disubstituted uracils, which were
      easily obtainable from uracil by preparation under alkali and Mitsunobu
      conditions, and examined their antiviral activity against HIV-1 and human
      cytomegalovirus (HCMV). We found that 1-benzyl-3-(3,5-dimethylbenzyl)uracil and 1
      cyanomethyl-3-(3,5-dimethylbenzyl)-4-thiouracil showed powerful inhibition
      against HCMV and HIV-1, respectively.

PMID- 14694992
TI  - Academic freedom, academic duty.

PMID- 14694991
TI  - Nucleoside reverse transcriptase inhibitor usage and the incidence of peripheral
      neuropathy in HIV/AIDS patients.
AB  - Peripheral neuropathy (PN) is a well-known adverse effect of treatment with
      nucleoside reverse transcriptase inhibitors (NRTIs). We performed a prospective
      follow-up study in HIV-infected patients on antiretroviral therapy containing
      NRTIs. The objective of this study was to examine the incidence of PN among
      patients using NRTI drugs. Data were obtained using medical records of patients
      continuously monitored for the efficacy and toxicity of antiretroviral therapy.
      The incident cases of PN were examined. Incidence rates of PN were calculated for
      each antiretroviral regimen that included zidovudine, zalcitabine, lamivudine,
      didanosine (ddI), stavudine (d4T) or didanosine+stavudine. Poisson regression was
      used to compare the relative risk of PN for each regimen. A total of 112 HIV
      infected patients were treated with at least one NRTI-containing regimen. Thirty
      two cases of PN were recorded. The lowest incidence rate (IR) of 0.13 per 100
      person-years occurred in patients treated with didanosine. The highest IR for PN
      occurred with the didanosine+stavudine combination (IR=0.18 per 100 person
      years). Compared to didanosine alone, the relative risk of PN was 1.77 (95%CI,
      0.52-2.12) for stavudine, and 1.76 (95%CI, 0.95-2.49) for didanosine+stavudine.
      Other risk factors for PN included a low CD4 cell count and female sex. Our data
      show that the risk of PN is almost twice as high when stavudine is used alone or
      in combination with didanosine. The use of stavudine alone or in combination with
      didanosine should probably not be routinely recommended if other treatment
      options are available.

PMID- 14694993
TI  - Nursing shortage update: effects on education and specialty areas.

PMID- 14694994
TI  - Clinical nursing competence of RN-to-BSN students in a nursing concept-based
      curriculum in Taiwan.
AB  - This 3-year longitudinal study used a questionnaire to evaluate the clinical
      nursing competence of RN-to-BSN students in a nursing concept-based curriculum in
      Taiwan. The research sample consisted of 52 full-time and 69 part-time RN-to-BSN
      students. A four-dimensional Clinical Nursing Competence Questionnaire was
      developed to measure student caring, communication/coordination,
      management/teaching, and professional self-growth competence. Results indicated
      full-time students' scores on self-evaluations of overall clinical nursing
      competence significantly increased with each successive evaluation (p < .05). The
      scores of part-time students fell significantly with successive evaluations, with
      the exception of professional self-growth competence (p < .01). Instructor
      evaluations generally showed no significant difference between the two groups.
      Student self-evaluations were significantly higher than instructor evaluations (p
      < .05). The results of this study may serve as a reference for nurse educators
      developing curricula for RN-to-BSN education.

PMID- 14694995
TI  - Establishing consensus about the baccalaureate entry-to-practice policy.
AB  - This article is based on the results of a qualitative study examining educational
      reforms in New Brunswick, Canada, during the 1980s. Using the province of New
      Brunswick as a case study, three issues related to the baccalaureate entry-to
      practice policy are examined. First, the process of upgrading nursing education
      to a baccalaureate degree and the conflict this change created between the Nurses
      Association of New Brunswick and the New Brunswick Nursing Union are described.
      Second, the reasons leaders of the professional nursing organization desired to
      upgrade nursing education are examined, and third, the issues underlying the
      conflict over nursing education are discussed.

PMID- 14694996
TI  - Mentoring for research skill development.
AB  - The nursing shortage is significantly affecting the nursing academic environment.
      A self-perpetuating cycle of insufficient numbers of faculty with inadequate
      preparation for academia could lead to a profound decline in the nursing
      profession. Institutions often implement mentoring plans for new tenure track
      faculty, and the challenge is even greater in environments that are not research
      intensive. This article describes the implementation of the research arm of an
      institutional mentoring plan for new tenure track faculty. The plan was designed
      to facilitate new faculty's attainment of tenure, while expediting the
      development of a satisfying career in academia. Doctoral education does not
      necessarily provide graduates with all the tools required to be successful
      researchers. However, specific guidance may be provided in the developing of a
      research program; creating networks and selecting consultants; preparing
      presentations and publications; and developing grantsmanship skills, particularly
      for institutions without established research centers.

PMID- 14694997
TI  - Lights! Camera! Action!: video projects in the classroom.
AB  - We report on two classroom video projects intended to promote active student
      involvement in their classroom experience during a year-long medical-surgical
      nursing course. We implemented two types of projects, Nursing Grand Rounds and
      FPBTV. The projects are templates that can be applied to any nursing specialty
      and can be implemented without the use of video technology. During the course of
      several years, both projects have proven effective in encouraging students to
      promote pattern recognition of characteristic features of common illnesses, to
      develop teamwork strategies, and to practice their presentation skills in a safe
      environment among their peers. The projects appealed to students because they
      increased retention of information and immersed students in the experience of
      becoming experts about an illness or a family of medications. These projects have
      enabled students to become engaged and invested in their own learning in the
      classroom.

PMID- 14694998
TI  - Sponsored professional seminars: enhancing professionalism among baccalaureate
      nursing students.
AB  - If we are to emphasize professionalism within nursing, students need to
      understand the opportunities, responsibilities, and concerns that are integral to
      the nursing profession. Sharing ideas related to nursing practice in a specified
      area with practicing nurses, expert faculty, and a speaker provide students with
      a sense of excitement about their chosen career. The sponsored seminar series
      permits undergraduate nursing students to converse with their future colleagues
      over dinner, develop lasting relationships, and advance their learning in an area
      of interest.

PMID- 14694999
TI  - Impact of long-acting growth factors on practice dynamics and patient
      satisfaction.
AB  - OBJECTIVE: To quantify time expended, patient satisfaction, and econometrics
      associated with short-acting (sargramostim, epoetin alfa) and long-acting
      (darbepoetin alfa, pegfilgrastim) growth factors. DESIGN: Retrospective resource
      utilization and prospective two-phase observational study. METHODS: During week
      1, time-motion measurements related to patient treatment and drug preparation
      were collected for scheduling; check-in; phlebotomy; laboratory; and drug
      preparation, administration, and recording. Drug utilization for one chemotherapy
      cycle during weeks 2 and 3 was assessed for sargramostim, pegfilgrastim, epoetin
      alfa, darbepoetin alfa, sargramostim plus epoetin alfa, and pegfilgrastim plus
      darbepoetin alfa. Patients completed a satisfaction survey. RESULTS: Among 140
      patients (mean age 58 yrs), mean chemotherapy cycle duration was 19 days. A total
      of 268 events were observed. Mean total staff time/patient visit for drug
      administration was 22.1 minutes, with most time spent on scheduling (5.5 min) and
      drug preparation, administration, recording (5.2 min). For sargramostim only
      versus pegfilgrastim only, pegfilgrastim resulted in a 37% reduction (p < 0.01)
      in all visits and an 85% reduction (p < 0.01) in mean number of doses. For
      epoetin alfa only versus darbepoetin alfa only, darbepoetin alfa resulted in a
      48% reduction (p < 0.01) in mean number of doses. The most common dosage of
      epoetin alfa was 40,000 U/week (63.6%) and that of darbepoetin alfa was 200
      microg every other week (92%), but complete blood counts were obtained weekly.
      For pegfilgrastim plus darbepoetin alfa versus sargramostim plus epoetin alfa, a
      45% reduction (p < 0.01) in total visits and a 77% reduction (p < 0.01) in mean
      number of doses were noted in the former group. In 69 patients converted to long
      acting drugs, 65 actual hours for a single treatment cycle were saved. For
      patients receiving pegfilgrastim plus darbepoetin alfa, there was a 45% reduction
      in total clinic visits, 77% reduction in doses, and staff time savings of 1.9
      hours/patient/cycle of chemotherapy. Fifty-four patients completed the survey and
      trended toward neutral in their responses, with moderate disagreement that
      receiving injections is painful. CONCLUSION: Long-acting growth factors resulted
      in significant time savings for staff and providers by reducing the number of
      necessary office visits for drug administration. These time savings can
      significantly improve the quality of life for patients, as well as nurses,
      physicians, and caregivers.

PMID- 14695000
TI  - Guidelines for using darbepoetin alfa in patients with chemotherapy-induced
      anemia.
AB  - Anemia is an undertreated but common complication of cancer and is associated
      with debilitating symptoms that impair the patient's ability to perform daily
      functions of life. Treatment with darbepoetin alfa, a novel erythropoiesis
      stimulating protein, is appropriate for chemotherapy-induced anemia. Guidelines
      on darbepoetin alfa therapy will assist clinicians in its appropriate
      application. Other causes of anemia in patients with cancer should be
      investigated and corrected before therapy with darbepoetin alfa is begun.
      Patients with hemoglobin levels below 11 g/dl are candidates for immediate
      therapy. For patients receiving chemotherapy who have declining hemoglobin levels
      but less severe anemia (< 12 but > or = 11 g/dl), the decision to treat
      immediately should be determined by the clinical circumstances. The preferred
      initial dosage for darbepoetin alfa is 200 microg every 2 weeks; 100 microg/week
      is an acceptable alternative. Dosages should be titrated to maintain hemoglobin
      levels at or near 12 g/dl. Reasons for failure to respond to darbepoetin alfa
      should be investigated before discontinuing therapy. Clinicians should consider
      discontinuing therapy if the hemoglobin level has not increased by 1 g/dl or more
      at 6-8 weeks after appropriate dosage adjustments or the number of red blood cell
      transfusions has not decreased.

PMID- 14695001
TI  - Considerations in darbepoetin alfa cost and reimbursement: a model for pharmacy
      managers.
AB  - With health care administrators focusing on the financial aspects of patient
      care, pharmacy budget managers must be able to evaluate all financial
      implications of drugs under formulary review. Clinical considerations, dosing
      equivalency, direct and indirect costs, payer mix, and reimbursement level are
      issues that should be considered by a multidisciplinary team. A pharmacoeconomic
      evaluation of darbepoetin alfa compared with epoetin alfa is presented as a model
      to help pharmacy budget managers address these issues and develop an evaluation
      of two high-cost drugs to determine which would be the better agent to have on
      their formulary.

PMID- 14695002
TI  - Watch for radiation.

PMID- 14695003
TI  - Model results of kidney burdens from uranium intakes.
AB  - Uranium is a naturally occurring element, which is both radiologically and
      chemically toxic. When dealing with intakes of uranium, whether natural or
      depleted, chemical toxicity to the kidney usually predominates over radiological
      toxicity. This is especially true for uranium compounds in soluble (inhalation
      Type F) and moderately soluble (inhalation Type M) forms. To assess chemical
      toxicity, information on kidney burden per unit intake is required. This study
      summarizes the kidney burdens per unit intake for common exposures from uranium
      ingestion and inhalation. ICRP models developed for radiation dosimetry purposes
      can equally well be used to estimate kidney burdens from uranium intakes. While
      dosimetric quantities and data are tabulated in ICRP publications, data on
      uranium burdens in kidney are not explicitly given in these tabulations. In this
      work, the most recent ICRP models were utilized to generate a compilation of
      kidney burdens from common intakes. Calculations were made for four age groups
      from infant to adult. For all age groups, long-term chronic uranium ingestion
      will result in a kidney burden of 6.6% of daily uranium intake. Comparisons of
      kidney burdens due to acute ingestion and acute inhalation show that inhaled
      uranium compounds of Type F and Type M will generally result in higher burdens to
      kidney compared to the same amount of uranium compounds ingested.

PMID- 14695004
TI  - Detection of depleted uranium in urine of veterans from the 1991 Gulf War.
AB  - American soldiers involved in "friendly fire" accidents during the 1991 Gulf War
      were injured with depleted-uranium-containing fragments or possibly exposed to
      depleted uranium via other routes such as inhalation, ingestion, and/or wound
      contamination. To evaluate the presence of depleted uranium in these soldiers
      eight years later, the uranium concentration and depleted uranium content of
      urine samples were determined by inductively coupled plasma mass spectrometry in
      (a) depleted uranium exposed soldiers with embedded shrapnel, (b) depleted
      uranium exposed soldiers with no shrapnel, and (c) a reference group of deployed
      soldiers not involved in the friendly fire incidents. Uranium isotopic ratios
      measured in many urine samples injected directly into the inductively coupled
      plasma mass spectrometer and analyzed at a mass resolution m/delta m of 300
      appeared enriched in 235U with respect to natural abundance (0.72%) due to the
      presence of an interference of a polyatomic molecule of mass 234.81 amu that was
      resolved at a mass resolution m/delta m of 4,000. The 235U abundance measured on
      uranium separated from these urines by anion exchange chromatography was clearly
      natural or depleted. Urine uranium concentrations of soldiers with shrapnel were
      higher than those of the two other groups, and 16 out of 17 soldiers with
      shrapnel had detectable depleted uranium in their urine. In depleted uranium
      exposed soldiers with no shrapnel, depleted uranium was detected in urine samples
      of 10 out of 28 soldiers. The median uranium concentration of urines with
      depleted uranium from soldiers without shrapnel was significantly higher than in
      urines with no depleted uranium, though substantial overlap in urine uranium
      concentrations existed between the two groups. Accordingly, assessment of
      depleted uranium exposure using urine must rely on uranium isotopic analyses,
      since urine uranium concentration is not an unequivocal indicator of depleted
      uranium presence in soldiers with no embedded shrapnel.

PMID- 14695005
TI  - Electron absorbed fractions based on a new model of the anterior nasal passage.
AB  - In a previous work we reported that the fraction of the electron energy absorbed
      in the basal cell layer of the anterior nasal passages was not very sensitive to
      changes in the surface area or radius of the cylindrical model adopted in
      Publication 66 of the International Commission on Radiological Protection. These
      absorbed fraction data are used in calculation of the dose to a 10-microm-thick
      basal cell layer located at a depth of 40 microm in the epithelial cell layer of
      the extrathoracic (ET1) region. However, these data may only be applicable to the
      assumed cylindrical geometry and may not be valid for more realistic ET1
      geometries. The nose differs in size and shape from one person to another, its
      shape is not cylindrical but closer to a truncated elliptical cone, and in most
      humans the nostrils are elliptical in shape. We propose herein a more realistic
      geometry model, the frustum of a cone, for the anterior nose region (ET1) as an
      alternative to the cylinder model provided in ICRP 66. The results of absorbed
      fraction calculations using MCNP4B with the new model are reported. These
      absorbed fractions are compared to the values previously obtained using the
      MCNP4B code and a cylindrical model (10 cm2 surface area). We also investigate
      the effects of changing the size of the truncated cone to represent variations
      due to sex and age.

PMID- 14695006
TI  - Comparison of retrospective luminescence dosimetry with computational modeling in
      two highly contaminated settlements downwind of the Chernobyl NPP.
AB  - The cumulative absorbed dose in bricks collected from six buildings in two
      heavily contaminated settlements (137Cs > 2,000 kBq m(-2)) located downwind of
      the Chernobyl Nuclear Power Plant was determined using luminescence techniques by
      six laboratories. The settlements, Vesnianoje in Ukraine and Zaborie in Russia,
      are located in, respectively, proximal and distal locations relative to the
      Chernobyl Nuclear Power Plant. The luminescence determinations of cumulative dose
      in brick, after subtraction of the natural background dose, were translated to
      absorbed dose in air at a Reference Location using conversion factors derived
      from Monte Carlo simulations of photon transport. The simulations employed source
      distributions inferred from contemporary soil contamination data and also took
      into account heterogeneity of fallout deposition. This translation enables the
      luminescence determinations to be compared directly with values of cumulative
      absorbed dose obtained by computational modeling and also other dose
      reconstruction methods. For each sampled location the cumulative dose was
      calculated using three deterministic models, two of which are based on the
      attenuation of dose-rate with migration of radionuclides in soil and the third on
      historic instrumental gamma dose-rate data. The results of the comparison of the
      two methods indicate overall agreement within margins of +/-25%. The methodology
      developed is generally applicable and adaptable to areas contaminated by much
      lower levels of radioactive fallout in which brick buildings are found.

PMID- 14695007
TI  - Biokinetic model of radium in humans and beagles.
AB  - A compartmental model of the distribution of radium in humans and young adult
      beagle dogs (approximately 500-550 d) is presented. The model consists of one
      soft tissue compartment and seven skeletal compartments for humans, and five
      skeletal compartments for beagles. The number of transfer parameters to be
      estimated was reduced by using remodeling rates of bone and imposing several
      constraints deduced from known features of bone physiology, radium metabolism,
      and autoradiographic analyses. The model predictions are in good agreement with
      measured retentions in plasma, whole body, skeleton, and soft tissues of both
      species. Moreover, for beagles even the retention in individual bones can be
      predicted quite well if the relevant morphometric parameters are known. While
      some of the estimated transfer parameters are similar in both species, others
      differ by an order of magnitude or more. Wherever possible, a comparison of model
      parameters with those of previous models is given. The new model not only is
      instrumental for calculating local doses in the skeleton but also can be used for
      characterizing the microdistribution of radium in this organ.

PMID- 14695008
TI  - Assessment of the magnetic field exposure due to the battery current of digital
      mobile phones.
AB  - Hand-held digital mobile phones generate pulsed magnetic fields associated with
      the battery current. The peak value and the waveform of the battery current were
      measured for seven different models of digital mobile phones, and the results
      were applied to compute approximately the magnetic flux density and induced
      currents in the phone-user's head. A simple circular loop model was used for the
      magnetic field source and a homogeneous sphere consisting of average brain tissue
      equivalent material simulated the head. The broadband magnetic flux density and
      the maximal induced current density were compared with the guidelines of ICNIRP
      using two various approaches. In the first approach the relative exposure was
      determined separately at each frequency and the exposure ratios were summed to
      obtain the total exposure (multiple-frequency rule). In the second approach the
      waveform was weighted in the time domain with a simple low-pass RC filter and the
      peak value was divided by a peak limit, both derived from the guidelines
      (weighted peak approach). With the maximum transmitting power (2 W) the measured
      peak current varied from 1 to 2.7 A. The ICNIRP exposure ratio based on the
      current density varied from 0.04 to 0.14 for the weighted peak approach and from
      0.08 to 0.27 for the multiple-frequency rule. The latter values are considerably
      greater than the corresponding exposure ratios 0.005 (min) to 0.013 (max)
      obtained by applying the evaluation based on frequency components presented by
      the new IEEE standard. Hence, the exposure does not seem to exceed the
      guidelines. The computed peak magnetic flux density exceeded substantially the
      derived peak reference level of ICNIRP, but it should be noted that in a near
      field exposure the external field strengths are not valid indicators of exposure.
      Currently, no biological data exist to give a reason for concern about the health
      effects of magnetic field pulses from mobile phones.

PMID- 14695009
TI  - Partial site release at a power reactor facility.
AB  - U.S. NRC licensed facilities undergoing decommissioning may wish to remove
      portions of their site from the jurisdiction of their license, prior to final
      license termination. The method of partial site release, relevant to radiological
      conditions, described herein employs NUREG-1505 methodology for demonstrating
      indistinguishability from background. The partial site release process was also
      informed by NRC Regulatory Issue Summary 2000-19 "Partial Release of Reactor Site
      for Unrestricted Use Before NRC Approval of the License Termination Plan."
      However, the focus of this discussion is the radiological aspects of partial site
      release, relevant to the implementation of NUREG-1505 methodology for
      demonstrating indistinguishability from background, based on the 137Cs
      concentrations at the site and a suitable background reference area. This type of
      approach was found acceptable by the NRC, and the partial site release was
      granted.

PMID- 14695010
TI  - Curve fitting air sample filter decay curves to estimate transuranic content.
AB  - By testing industry standard techniques for radon progeny evaluation on air
      sample filters, a new technique is developed to evaluate transuranic activity on
      air filters by curve fitting the decay curves. The industry method modified here
      is simply the use of filter activity measurements at different times to estimate
      the air concentrations of radon progeny. The primary modification was to not look
      for specific radon progeny values but rather transuranic activity. By using a
      method that will provide reasonably conservative estimates of the transuranic
      activity present on a filter, some credit for the decay curve shape can then be
      taken. By carrying out rigorous statistical analysis of the curve fits to over 65
      samples having no transuranic activity taken over a 10-mo period, an optimization
      of the fitting function and quality tests for this purpose was attained.

PMID- 14695011
TI  - The LNTH is doing more harm than good.

PMID- 14695012
TI  - Computed Mayak neutron doses.

PMID- 14695013
TI  - Evaluation of patient and staff doses during various CT fluoroscopy guided
      interventions.

PMID- 14695014
TI  - Transuranic isotopes and 90Sr in attic dust in the vicinity of two nuclear
      establishments in northern Germany.

PMID- 14695015
TI  - IAEA DG calls for new security framework.

PMID- 14695016
TI  - More harm than good? Diagnostic codes for child and adult abuse.
AB  - This study sought to understand the reasons for the lack of use of ICD diagnostic
      codes for child and adult abuse. New Jersey professionals were recruited to
      participate in three focus groups on child abuse, adult or primarily woman abuse,
      and elder abuse. Participants included health care providers, advocates from the
      community, and representatives of state agencies and the insurance industry.
      Concerns about coding abuse included further jeopardizing victims/patients,
      diagnostic uncertainty, and lack of resources. Members of the child abuse group
      were somewhat more receptive to coding abuse. Reasons to code, such as for
      documentation and reimbursement were discussed and rebutted. Most participants
      concluded that use of the abuse codes should be judicious because they have the
      potential to do more harm than good. More research is needed on the implications
      of coding for victims/patients along with medical education in the identification
      of abuse in general and coding abuse in particular.

PMID- 14695017
TI  - Sex differences in empathy and its relation to juvenile offending.
AB  - Implicit in most theoretical accounts of sex differences in offending is the
      assumption that females are less likely than males to engage in crime--especially
      serious, violent crime--in part because of their comparatively higher levels of
      concern for others and stronger affiliative ties. Much research suggests that
      significant sex differences in both empathy and serious offending emerge in
      adolescence, with females displaying notably higher levels of empathy and males
      engaging in notably higher levels of serious offending. However, there has been
      little empirical work assessing the degree to which sex differences in empathy
      among adolescents can account for sex differences in offending. This research
      uses data from a sample of adolescents attending public high schools in
      Philadelphia (n = 425) and a sample of adolescents incarcerated in the California
      Youth Authority (CYA) (n = 232) to examine the relation between empathy and
      serious offending. Results suggest that empathy acts as a protective factor for
      both males and females but that there are subtle differences among males and
      females in the relation between empathy and offending.

PMID- 14695018
TI  - The "homogamy" of road rage: understanding the relationship between victimization
      and offending among aggressive and violent motorists.
AB  - The issue of "road rage" has received increasing media and scholarly attention in
      recent years. Using a representative sample of 2610 adults from Ontario,
      involvement with road rage was surveyed across demographic subgroups. Incidents
      of road rage were divided into two categories, verbal-gesturing road rage and
      physical-threats road rage. Drawing upon violence and criminological literature,
      experiences of road rage victimization and offending were explored, as well as
      the extent to which individuals were simultaneously the victims and perpetrators
      of road rage. Results challenge findings from the violence literature that males
      and young adults have the greatest propensity for violent victimization. Road
      rage offending was predominantly a male activity, while there were no gender
      differences in victimization. Moreover, road rage was not isolated among young
      adults; rather, road rage was prominent across all ages, with the exception of
      seniors. Consistent with the existing literature, road rage was higher in urban
      settings.

PMID- 14695019
TI  - Masculine gender role stress and men's fear of emotions as predictors of self
      reported aggression and violence.
AB  - To test the hypothesis that relationship violence may be related to men's fear of
      emotions, a secondary data analysis examined a sample of 155 male students
      attending an Eastern urban university. The men had been assessed using measures
      of masculine gender role stress, fear of emotions, and self-reported perpetration
      of relationship violence. Men's fear of emotion predicted relationship violence
      beyond what was accounted for masculine gender role stress. In addition, men's
      fear of emotions was found to partially mediate the relationship between
      masculine gender role stress and relationship violence. Results are discussed in
      terms of implications for future research and clinical interventions.

PMID- 14695020
TI  - The context of sexual violence: situational predictors of self-protective
      actions.
AB  - While considerable research has examined the relative effectiveness of different
      types of self-protective actions in rape avoidance, little research has
      considered how the situational context of the assault affects women's choice of
      self-protective strategy. Through an examination of data from the National Crime
      Victimization Survey, this article examines the extent to which situational
      factors are independently related to the use of physical resistance, verbal
      resistance, as well as to lack of resistance. The results of the multinominal
      logistic regression analysis indicate that those who used verbal self-protective
      action were more likely to have been attacked at night, threatened with a weapon,
      and to be assaulted by a prior or current romantic partner than were those who
      chose physical resistance. Those attacked by a current or former intimate were
      also more likely to employ no resistance than they were physical resistance.
      Victims facing a substance-using assailant, however, were more likely to enact
      physical self-protection than to employ no resistance.

PMID- 14695021
TI  - Demographic, psychosocial, and personality characteristics of lesbian batterers.
AB  - Prevalence of domestic violence (DV) in lesbian and heterosexual relationships
      appears to be similar. Despite this, few studies have examined factors associated
      with DV in lesbian relationships, and even fewer have examined characteristics of
      lesbian batterers. Demographic and psychosocial characteristics and personality
      traits were examined in 100 lesbians in current relationships (33 Batterers and
      67 Nonbatterers). Results indicated that Batterers were more likely to report
      childhood physical and sexual abuse and higher rates of alcohol problems. Results
      from the MCMI-III indicated that, after controlling for Debasement and
      Desirability indices, Batterers were more likely to report aggressive,
      antisocial, borderline, and paranoid personality traits, and higher alcohol
      dependent, drug-dependent, and delusional clinical symptoms compared to
      Nonbatterers. These results provide support for social learning and
      psychopathology theoretical models of DV and clinical observations of lesbian
      batterers, and expand our current DV paradigms to include information about same
      sex DV.

PMID- 14695022
TI  - Does writing reduce posttraumatic stress disorder symptoms?
AB  - To see if writing about their trauma lessened PTSD and related symptoms, 57
      undergraduates, previously screened for traumatic experiences, wrote for 15
      minutes on 4 days across 2 weeks about either their trauma or a trivial topic.
      They reported PTSD, impact, suicide ideas, dissociation, and depression pre-,
      post-, and at 6-week follow-up testing. Trauma and trivial writers were not
      different. Surprisingly, at follow-up everyone reported less severe PTSD
      symptoms, impact, and dissociation, and fewer health visits, but about the same
      suicidal ideation and depression. On PTSD symptoms and impact, the pattern of
      improvement was different: Those writing about trauma got worse at posttesting,
      but improved to better than their initial state by follow-up. Those writing about
      a trivial topic got better by posttesting, and held that position at follow-up.
      In this project, writing seemed to reduce PTSD symptoms regardless of whether it
      concerned the trauma or what they ate for lunch.

PMID- 14695023
TI  - Violence against women with physical disabilities.
AB  - This study explored risk factors for violence among a sample of adult women with
      physical disabilities. Fifty-six percent (100) of the 177 women participating in
      the study indicated a positive history of abuse. Of the women who reported abuse,
      most reported multiple abuse situations and abusers who were typically their male
      partners. In addition, only a small proportion of women sought and received
      adequate help. Women who indicated that they did not seek help were asked why
      this was the case. Their responses included: feeling that they could handle it
      themselves, having other sources of support available, being unaware of where to
      go, feeling embarrassed, feeling guilty about being a burden or that it was their
      fault, fear that abuser would come after them, fear of not being believed, and,
      to a lesser extent, concern that the shelter would lack appropriate
      accommodations. These findings highlight the importance of intervention
      strategies including advocacy activities for women with disabilities, activities
      with schools, activities to deter and prevent partner and caregiver violence,
      community awareness activities, and dissemination activities.

PMID- 14695024
TI  - Difference in signal transduction mechanisms involved in 5-hydroxytryptamine- and
      U46619-induced vasoconstrictions.
AB  - In order to elucidate the signal transduction pathways of vascular smooth muscle
      contractions induced by stimulation of receptors for 5-hydroxytryptamine (5-HT)
      and thromboxane A2 (TXA2), both of which are released from activated platelets,
      we examined whether protein kinases, such as tyrosine kinase, p38 mitogen
      activated protein kinase (MAPK) and protein kinase C (PKC), are involved in the
      contraction produced by either 5-HT or U46619 (an analog of TXA2) in the rat
      aorta. Both 5-HT and U46619 induced sustained contractions, which were markedly
      reduced in the absence of extracellular Ca2+. Verapamil (a L-type Ca2+ channel
      blocker) markedly inhibited the contractile response to 5-HT, while the U46619
      induced contraction was only slightly inhibited by verapamil. Both contractile
      responses to 5-HT and U46619 were significantly inhibited by calphostin C (a PKC
      inhibitor). On the other hand, both genistein (5 microM, a tyrosine kinase
      inhibitor) and SB203580 (a p38 MAPK inhibitor) significantly inhibited 5-HT
      induced contractions but had little effects on the contractions induced by
      U46619. These results suggest that the signal transduction mechanisms involved in
      the contractions mediated via 5-HT and TXA2 receptors are different as follows.
      Both the tyrosine kinase and p38 MAPK pathways are involved in 5-HT contraction
      but not in TXA2 contraction, while both contractions are strongly dependent on
      transplasmalemmal Ca2+ entry. The contractile responses to both 5-HT and TXA2
      involve voltage-dependent Ca2+ channels and PKC.

PMID- 14695025
TI  - Electrophysiological properties of inhibitory junction potential in murine lower
      oesophageal sphincter.
AB  - The electrophysiological properties of smooth muscle in the murine lower
      oesophageal sphincter (LOS) were investigated by intracellular microelectrode
      recording. Inhibitory junction potentials (IJPs) evoked by trains of field
      stimulation (30 V, 0.2-0.3 ms, 10 stimuli at 1-50 Hz) were observed in the murine
      LOS in the presence of atropine (1 microM) and nifedipine (1 microM). The IJP
      consists of two components, which we termed fast IJP and slow IJP. The fast IJP
      was partly sensitive to guanethidine (5 microM), pyridoxalphosphate-6-azophenyl
      2',4'-disulphonic acid (PPADS, 30 microM) and apamin (0.1 microM), suggesting
      that the fast IJP was produced partly through the activation of apamin-sensitive
      Ca2+-activated K+ channels and of P2-purinoceptors. The other part of the fast
      IJP was sensitive to N(omega)-nitro-L-arginine (L-NNA, 100 microM) and 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, 1 microM), but insensitive to
      apamin (0.1 microM), iberiotoxin (50 nM) and charybdotoxin (30 nM). Slow IJP was
      sensitive to L-NNA (100 microM), ODQ (10 microM) and glibenclamide (10 microM),
      but insensitive to apamin (0.1 microM), iberiotoxin (50 nM) and charybdotoxin (30
      nM). KT5823, a protein kinase G (PKG) inhibitor, had no effect on the fast and
      slow IJP in this tissue. It was suggested that, in the mouse LOS, adenosine
      trisphosphate (ATP) partly mediated the fast UP through apamin-sensitive Ca2+
      activated K+ channels, and nitric oxide mediated the remained part of the fast
      IJP and the slow IJP through cGMP, but not PKG. ATP-sensitive K+ channels were
      suggested to be partly involved in the production of slow IJP, but the
      responsible channel(s) for the nitrergic fast IJP remained unclarified.

PMID- 14695026
TI  - Gut pacemaker cells: the interstitial cells of Cajal (ICC).
AB  - This review will focus on the pacemaker mechanisms underlying gastrointestinal
      autonomic rhythmicity in an attempt to elucidate the differences and similarities
      between the pacemaker mechanisms in the heart and gut. Interstitial cells of
      Cajal (ICC) form networks that are widely distributed within the submucosal (ICC
      SM), intra-muscular (ICC-IM, ICC-DMP) and inter-muscular layers (ICC-MY) of the
      gastrointestinal tract from the esophagus to the internal anal sphincter. The ICC
      generate spontaneously active pacemaker currents that may be recorded as plateau
      and slow potentials. These pacemaker currents drive the spontaneous electrical
      and mechanical activities of smooth muscle cells. The enteric nervous system,
      composed of both the myenteric (inter-muscular) plexus and the submucosal plexus,
      is also distributed in the gastrointestinal tract from the esophagus to the
      internal anal sphincter. The role of the ICC and the enteric nervous system in
      the integrative control of gastrointestinal function and especially of
      spontaneous rhythmic activity, is still unknown. Nevertheless, at least from the
      results presented in this review of studies of the jejunum, ileum and proximal
      colon of the mouse, it is convincing that the ICC drive spontaneous rhythmic
      motility, although a role for the enteric nervous system in the regulation of
      spontaneous rhythmic motility cannot be overlooked. Furthermore, intracellular
      Ca2+ handling has a critical role in the generation of pacemaker activity in the
      gut and heart, although respective players such as the Ca2+-ATPase of the
      sarcoplasmic reticulum (endoplasmic reticulum), IP3 receptors, ryanodine
      receptors and plasma membrane ion channels may have divergent roles in the Ca2+
      release refilling cycles. In conclusion, intracellular Ca2+ handling plays a key
      role in the gut pacemaker responsible for spontaneous rhythmicity, as well as in
      the cardiac pacemaker responsible for spontaneous beating. Pharmacotherapeutic
      targeting of intracellular Ca2+ handling mechanisms may be a promising approach
      to the treatment and cure of gut motility dysfunction.

PMID- 14695027
TI  - Electrophysiological properties of gastric pacemaker potentials.
AB  - Electrophysiological properties of pacemaker potentials recorded from myenteric
      interstitial cells of Cajal (ICC-MY) within the guinea-pig gastric antrum are
      reviewed briefly. Pacemaker potentials consist of two components, a primary
      component forming a transient depolarization with a rapidly rising initial phase,
      followed by a secondary component as a plateau with sustained depolarization. The
      primary component is inhibited by low [Ca2+]o solutions or depolarization of the
      membrane with high [K+]o solutions. This inhibition could be mimicked by
      chelating [Ca2+]i with BAPTA-AM, suggesting that this component is produced by
      activation of voltage-dependent Ca2+ permeable channels. The plateau component is
      inhibited by low [Cl-]o solution or DIDS, an inhibitor of Ca2+-activated Cl(-)
      channels, suggesting that this component is formed by Ca2+-activated Cl(-)
      currents. Reduction of Ca2+ release from internal stores by inhibiting the
      internal Ca-pump with cyclopiazonic acid results in a shortened duration of the
      plateau component, with no alteration in the rate of rise of the primary
      component. 2-APB, an inhibitor of the IP3-receptor mediated Ca2+ release from
      internal stores, abolishes pacemaker potentials, suggesting that the release of
      Ca2+ from internal IP3-sensitive Ca2+ stores is required for generation of
      pacemaker potentials. CCCP, a mitochondrial protonophore, depolarizes the
      membrane and abolishes pacemaker potentials, suggesting that mitochondrial Ca2+
      handling functions may be coupled with generation of pacemaker potentials. These
      results indicate that the two components of pacemaker potentials are generated by
      different mechanisms; the primary component may be produced by activation of
      voltage-dependent Ca2+-permeable channels, while the plateau component may be
      produced by the opening of Ca2+-activated Cl(-)-channels. It is hypothesized that
      pacemaker potentials are initiated by depolarization of the membrane due to
      generation of unitary potentials in response to mitochondrial Ca2+ handling.
      Activation of voltage-dependent Ca2+ influx, IP3-receptor mediated Ca2+ release
      from the internal stores and Ca2+-activated Cl(-)-channels may be involved as
      successive steps downstream to the generation of unitary potentials.

PMID- 14695028
TI  - Sino-atrial nodal cells of mammalian hearts: ionic currents and gene expression
      of pacemaker ionic channels.
AB  - The cardiac pacemaker is a sino-atrial (SA) nodal cell. The signal induced by
      this pacemaker is distributed over the heart surface by a specialised conduction
      system and is clinically recorded as the ECG. The SA nodal cells are highly
      resistant to cardiac failure and ischemia. Under calcium overload conditions,
      some dysrythmias of SA nodal cells occur easily. Morphological analysis under
      these conditions shows swelling of the cisternae of the Golgi apparatus, with
      little or no other histological change or damage being observed. The rate of
      sinus rhythm is quite different between various species. The investigations of SA
      nodal cells have so far clarified the pacemaker mechanisms involved. A number of
      ionic channel currents or pacemaker currents, contribute to the depolarization of
      the pacemaker potential (phase 4). This will not occur with a single current.
      Recent experiments have identified several novel pacemaker currents and have also
      revealed several differences in the pacemaker currents between species. The
      marked hyperpolarization-activated inward current (I(f)) appears in SA nodal
      cells of most species, while the inwardly rectifying K+ current (I(K1)) with
      masked I(f) current is found in those of the rat and monkey. In addition, the
      rapidly activated current (I(Kr)) and slowly activated current (I(Ks)) of the
      delayed rectifier K+ current (I(K)) contribute to the pacemaker potential in
      guinea pig SA nodal cells, with only the I(Ks) current in porcine SA nodal cells
      and only the I(Kr) current in the rat and rabbit. These differences in ionic
      channels presumably result from differences in gene expression. Some smooth
      muscle cells also possess the capacity to beat spontaneously. Uterine smooth
      muscle cells also exhibit an I(f) current. The basal mechanism for spontaneous
      activity in both SA nodal cells and smooth muscle cells is almost the same, but
      some differences in the ionic channels and their genetic expression may
      contribute to their respective pacemaker currents.

PMID- 14695029
TI  - Pacemaker mechanism of porcine sino-atrial node cells.
AB  - In cardiac sino-atrial node (SAN) cells, time- and voltage-dependent changes in
      the gating of various ionic currents provide spontaneous, stable and repetitive
      firing of action potentials. To address the ionic nature of the species-dependent
      heart rate, action potentials and membrane currents were recorded in single cells
      dissociated from the porcine SAN, and compared with those from SAN cells of
      rabbits, guinea-pigs and mice. The porcine SAN cells exhibited spontaneous
      activity with a frequency of 60-80 min(-1), which was much slower than that of
      rabbit SAN cells. Under voltage clamp conditions, depolarization activated the L
      type Ca2+ current (I(CaL)) followed by a gradual activation of the delayed
      rectifier K+ current (I(K)) while hyperpolarization activated the
      hyperpolarization-activated cation current (I(h)). It was found that the major
      component of I(K) in porcine SAN is the slowly activating I(K) (I(Ks)), in
      contrast to SAN cells of the rabbit and other species in which the rapid I(K)
      (I(Kr)) plays an active role in repolarization and the subsequent pacemaker
      depolarization. Replacement of rabbit I(Kr) with porcine I(Ks) and a slight
      modification in the gating parameters and amplitudes of other current systems in
      the 'Kyoto Model' gave an adequate reconstruction of spontaneous action
      potentials as well as of the voltage clamp recordings. We conclude that the
      density and the kinetics of I(K) contribute, in part, to the different heart
      rates of various species.

PMID- 14695030
TI  - Autism and measles-mumps-rubella (MMR) vaccination: a challenge for
      pharmacoepidemiology.

PMID- 14695031
TI  - Epidemiology and possible causes of autism.
AB  - OBJECTIVES: To review the recent literature on possible causes of the increase in
      frequency of diagnosed autism reported from three countries, and to compare the
      medical diagnoses and drug therapy from a new series of autistic boys and their
      mothers with that of comparable nonautistic boys and their mothers. DESIGN: Case
      control evaluation. PARTICIPANTS: Members of over 250 general practices in the
      United Kingdom. MEASUREMENTS AND MAIN RESULTS: Frequency of exposure to drugs and
      presence of preexisting clinical illnesses in autistic children and their mothers
      were compared with nonautistic children and their mothers over time. According to
      published studies, the incidence of boys diagnosed with autism rose dramatically
      in the 1990s. Numerous published studies have concluded that the measles-mumps
      rubella vaccine is not responsible for the large rise in diagnosed autism. In our
      study, boys diagnosed with autism had medical and drug histories, such as
      vaccines, before diagnosis, that were closely similar to those of nonautistic
      boys, except that developmental and sensory disorders were far more common in
      autistic boys. No material differences during pregnancy were found between the
      mothers of autistic boys and those of nonautistic boys in relation to illness or
      drug therapy. In the early 1990s, boys with diagnosed developmental disorders
      were infrequently diagnosed with autism. In the later 1990s, such boys more often
      were diagnosed with autism. CONCLUSION: A major cause of the recent large
      increase in the number of boys diagnosed with autism probably is due to changing
      diagnostic practices.

PMID- 14695032
TI  - Linezolid, levofloxacin, and vancomycin against vancomycin-tolerant and
      fluoroquinolone-resistant Streptococcus pneumoniae in an in vitro pharmacodynamic
      model.
AB  - STUDY OBJECTIVE: To compare the pharmacodynamic profiles of linezolid,
      levofloxacin, and vancomycin against clinical strains of Streptococcus
      pneumoniae, including vancomycin-tolerant and fluoroquinolone-resistant isolates.
      DESIGN: In vitro pharmacodynamic model. SETTING: Biosafety level 2, university
      research laboratory. BACTERIAL STRAINS: Ciprofloxacin-susceptible (79),
      ciprofloxacin-resistant (R921), and vancomycin-tolerant (P9802-020) clinical
      strains of S. pneumoniae. INTERVENTION: An in vitro pharmacodynamic model was
      used to simulate standard dosing regimens of linezolid, levofloxacin, and
      vancomycin against the isolates 79, R921, and P9802-020. MEASUREMENTS AND MAIN
      RESULTS: Bacterial density was profiled over 48 hours. Minimum inhibitory
      concentrations (MICs) for linezolid, levofloxacin, and vancomycin, respectively
      were 1, 1, 0.5 microg/ml for isolate 79; 1, 4, 0.5 microg/ml for R921; and 0.5,
      0.5, 0.5 microg/ml for P9802-020. Vancomycin minimum bactericidal concentration
      (MBC) values varied across large ranges for the tested strains. Linezolid
      achieved 99.9% kill against 79 and R921 by 24 and 28 hours, respectively.
      Levofloxacin achieved 99.9% kill against 79 and P9802-020 by 28 and 4 hours,
      respectively. Vancomycin achieved 99.9% kill against 79 and R921 by 8 and 24
      hours, respectively. Levofloxacin did not demonstrate activity against R921 at
      the 48-hour end point. Minimal kill (< 2 log) at 48 hours was noted for
      vancomycin and linezolid against P9802-020. Conclusion. Vancomycin tolerance
      appeared to be more reliably characterized by persistent viability in time-kill
      analyses than by MBC:MIC ratios. Vancomycin exhibited bactericidal activity
      against the non-vancomycin-tolerant strains of S. pneumoniae. Linezolid exhibited
      both bactericidal and bacteriostatic activity against all three strains tested,
      whereas levofloxacin demonstrated bactericidal activity against the
      fluoroquinolone-susceptible isolates. Further investigation of treatment
      alternatives for infections due to vancomycin-tolerant S. pneumoniae are needed.

PMID- 14695033
TI  - In vitro performance of two common valved holding chambers with a
      chlorofluorocarbon-free beclomethasone metered-dose inhaler.
AB  - STUDY OBJECTIVE: To compare in vitro aerosol deposition from a beclomethasone
      dipropionate metered-dose inhaler (MDI) containing hydrofluoroalkane propellant
      with that of the MDI in combination with two common valved holding chambers
      (VHCs) to evaluate how these VHCs affect the respirable dose of beclomethasone
      dipropionate. DESIGN: In vitro aerosol deposition study. SETTING: University
      research center. DEVICES: Beclomethasone dipropionate hydrofluoroalkane MDI
      alone, the MDI with OptiChamber VHC, and the MDI with AeroChamber-Plus VHC.
      INTERVENTION: The respirable dose (1-5-microm aerosol particles) of
      beclomethasone dipropionate was determined by sampling 10 80-microg actuations
      from five runs with each configuration (MDI alone, MDI with OptiChamber, and MDI
      with AeroChamber-Plus), using a well-established in vitro cascade impactor
      method. MEASUREMENTS AND MAIN RESULTS: Beclomethasone dipropionate aerosol was
      washed from the impactor with 50% methanol and quantified by means of high
      performance liquid chromatography. Differences among outcomes were determined by
      using analysis of variance. Mean beclomethasone dipropionate respirable dose from
      AeroChamber-Plus (27.2 +/- 10.0 microg/actuation) was not significantly different
      (p>0.05) from that of the MDI alone (29.0 +/- 7.0 microg/actuation). OptiChamber
      respirable dose (12.8 +/- 6.0 microg/actuation) was less than half that produced
      by either the AeroChamber-Plus or the MDI alone (p=0.013). CONCLUSIONS: The
      OptiChamber and AeroChamber-Plus VHCs do not demonstrate equivalent in vitro
      performance when used with a beclomethasone dipropionate MDI that contains
      hydrofluoroalkane propellant. The respirable dose of beclomethasone dipropionate
      aerosol from the hydrofluoroalkane MDI was decreased by only 6% when the MDI was
      mated to an AeroChamber-Plus VHC and by 56% when used with an OptiChamber VHC.

PMID- 14695034
TI  - Comparative pharmacokinetic analysis by standard two-stage method versus
      nonparametric population modeling.
AB  - STUDY OBJECTIVE: To compare the two-stage method, a widely used analytical method
      in pharmacokinetic studies, with nonparametric population modeling by using the
      same data set for determining the oral bioavailability of ribavirin. DESIGN:
      Pharmacokinetic analysis. Clinical research center. MATERIAL: Oral
      bioavailability data of ribavirin determined previously in six healthy adults.
      INTERVENTION: After 13C3-ribavirin 150 mg intravenously and unlabeled ribavirin
      400 mg orally had been given 1 hour apart, serial serum and urine samples were
      obtained for up to 169 hours. Concentrations of 13C3-ribavirin and unlabeled
      ribavirin in serum and urine were determined by a high-performance liquid
      chromatography tandem mass spectrometric method. MEASUREMENTS AND MAIN RESULTS:
      Serum and urine concentration-time profiles were comodeled with a three
      compartment model. The analysis was performed again by using the nonparametric
      population analysis technique. Serum ribavirin concentrations underwent Monte
      Carlo simulation for 1000 subjects receiving a single 600-mg oral dose. Both
      methods were similar in determining the mean +/- SD bioavailability (51.8 +/-
      21.8% by the two-stage method vs 54.8 +/- 16.4% by nonparametric modeling,
      p=0.79). However, the estimates of dispersion of model parameters and simulated
      drug exposures were substantially reduced by the population-modeling technique,
      as it takes into account covariance among model parameters and intersubject
      variability. CONCLUSION: Although the study sample was small, our parallel
      analyses of the same data set clearly demonstrated that more precise parameter
      estimates are likely to result with the population-modeling technique. Having
      accurate and precise estimation of population pharmacokinetic parameters and
      their true variances is crucial, as, at any dose, there'will be a lower
      probability of encountering a concentration-driven toxicity because of fewer
      outliers as the variance associated with the parameters decreases.

PMID- 14695035
TI  - Correlation of lamotrigine concentrations between serum and saliva.
AB  - STUDY OBJECTIVE: To compare the relationship between serum and salivary
      concentrations of lamotrigine in pediatric and adult epilepsy populations.
      DESIGN: Paired-sample pharmacokinetic study. SETTING: University neurology
      clinic. PATIENTS: Thirty-seven patients with epilepsy, aged 2-60 years, who were
      taking lamotrigine and whose physicians had ordered a lamotrigine serum
      concentration. MEASUREMENTS AND MAIN RESULTS: Patients spit a minimum of 0.25 ml
      into a cup to provide saliva samples. Blood samples were obtained by phlebotomy.
      Serum and salivary lamotrigine concentrations were determined by high-performance
      liquid chromatography. Linear regression analysis was used to evaluate
      correlations. Six patients' results were omitted due to the lack of a serum or
      saliva specimen or clearly erroneous results, leaving 31 patients for analysis.
      There was a strong correlation between the serum results reported by two
      reference laboratories (coefficient of correlation [r] = 0.988). The correlations
      between salivary and serum lamotrigine concentrations were similar for reference
      laboratory A (r = 0.81) and reference laboratory B (r = 0.84). Saliva:serum
      concentration ratios ranged from 0.41-1.26 (mean +/- SD 0.62 +/- 0.19) for
      reference laboratory A and from 0.40-1.19 ((mean +/- SD 0.64 +/- 0.18) for
      reference laboratory B. CONCLUSION: There is a good correlation between salivary
      and serum concentrations for lamotrigine. However, there is wide interpatient
      variability in the saliva:serum ratio. The data suggest that salivary monitoring
      may play a role in the monitoring of lamotrigine for adult and pediatric
      patients.

PMID- 14695036
TI  - Factors associated with long-term antibody production induced by hepatitis B
      vaccine in patients undergoing hemodialysis: a retrospective cohort study.
AB  - STUDY OBJECTIVE: To assess the influence of various clinical factors on antibody
      production induced by hepatitis B vaccine in patients receiving hemodialysis up
      to 24 months after vaccination. DESIGN: Retrospective cohort study. SETTING:
      Outpatient dialysis center. PATIENTS: Adult patients undergoing hemodialysis who
      received a three-dose series of intramuscular hepatitis B vaccine 40 microg at
      time 0, 1, and 6 months, according to protocol. MEASUREMENTS AND MAIN RESULTS:
      Antibody to hepatitis B surface antigen (anti-HBs) titers were monitored
      quarterly, and booster doses were given according to protocol. Patients with anti
      HBs of at least 10 mIU/ml were considered seropositive. Clinical variables--age,
      diabetes mellitus status, serum albumin level, and equilibrated Kt/V (eKt/V; Kt/V
      is a measure of urea clearance during dialysis, used to quantify the delivered
      dose of hemodialysis)--were compared between seropositive and seronegative
      patients 12 months (cohort 1) and 24 months (cohort 2) after vaccination. In
      cohort 1 (66 patients), 24 (36.4%) were seropositive at 12 months. In cohort 2
      (40 patients), 15 (37.5%) were seropositive at 24 months. Comparison of
      seropositive and seronegative patients revealed no statistically significant
      differences in mean age, sex, serum albumin level, or eKt/V. However, at 24
      months, patients with diabetes were 2.5 times more likely to demonstrate
      seropositivity than those without diabetes (60% vs 24%, respectively, p=0.02).
      CONCLUSION: Long-term seroprevalence induced by hepatitis B vaccine was low in
      our patients 12 and 24 months after vaccination. These results were comparable to
      previously reported long-term results. Larger, prospective studies would be
      needed to confirm the finding that patients with diabetes had superior hepatitis
      B vaccine-induced antibody production at 24 months.

PMID- 14695037
TI  - Clinical pharmacy specialist implementation of lisinopril therapy in patients
      with coronary artery disease and diabetes mellitus.
AB  - STUDY OBJECTIVE: As the results of the Heart Outcomes Prevention Evaluation trial
      suggested that patients with both coronary artery disease (CAD) and diabetes
      mellitus would benefit from angiotensin-converting enzyme (ACE) inhibitor
      therapy, our objective was to increase the percentage of patients with both of
      these conditions receiving the goal dosage (20 mg/day) or highest tolerated
      dosage of the ACE inhibitor lisinopril through intervention of a clinical
      pharmacy service. STUDY DESIGN: Prospective study with historic comparison
      (control group). SETTING: Clinical Pharmacy Cardiac Risk Service. PATIENTS:
      Hospitalized patients with CAD and type 2 diabetes mellitus. MEASUREMENTS AND
      MAIN RESULTS: At hospital discharge, lisinopril 5 mg/day was started in eligible
      patients; the drug was titrated to a goal dosage of 20 mg/day or the highest
      tolerated dosage. Potassium level, serum creatinine level, and blood pressure
      were monitored at baseline, at each dosage titration, and 2 weeks after the goal
      or highest tolerated dosage was reached. The group receiving usual care (control
      group) consisted of 95 patients; the treatment group had 101 patients. At
      baseline, 19 patients (20%) in the control group were receiving the goal dosage
      of lisinopril, 34 (36%) were taking a suboptimal dosage, 16 (17%) were excluded
      from treatment, and 26 (27%) were eligible but were not receiving lisinopril
      therapy. After 9 months, ACE inhibitor dosages had changed minimally in the
      control group. In the treatment group, at baseline, 37 patients (36%) were at
      their goal dosage and therefore titration was not necessary; 15 (15%) were
      receiving a suboptimal dosage, 35 (35%) were excluded from treatment, and 14
      (14%) were eligible but not receiving therapy. After the titration period, 55
      (54%) treatment group patients were at the goal dosage, 11 (11%) were taking a
      suboptimal dosage, and 35 (35%) were not candidates for ACE inhibitor therapy.
      The most common reasons for exclusion were renal insufficiency, cough, and
      baseline hypotension. Changes in potassium level, serum creatinine level, and
      blood pressure were not significant during the study. CONCLUSION: The clinical
      pharmacy service more than doubled the number of patients with CAD and diabetes
      who achieved the goal dosage of an ACE inhibitor, a drug class that has been
      shown to decrease morbidity and mortality in this patient population.

PMID- 14695038
TI  - New hormonal contraceptives: a comprehensive review of the literature.
AB  - Over 16 million women in the United States take oral hormonal contraceptives, yet
      approximately 5% experience an unintended pregnancy during the first year of use.
      Compliance with the regimen is important in maintaining cycle control and
      preventing pregnancy. New hormonal contraceptive agents, norelgestromin-ethinyl
      estradiol patch, etonogestrel-ethinyl estradiol vaginal ring, and
      medroxyprogesterone-estradiol cypionate injection, were designed to increase
      compliance and decrease adverse effects while maintaining efficacy. Each one has
      potential advantages for women seeking alternatives to traditional oral
      contraceptives or for those who have trouble remembering to take a daily pill.
      Each agent also may have its own disadvantages, including application site
      reactions, need for monthly injections, and device-related events; however, all
      have similar efficacy and adverse-effect profiles compared with current oral
      hormonal contraceptives.

PMID- 14695039
TI  - Invasive aspergillosis in patients with hematologic malignancies.
AB  - Invasive aspergillosis is an increasingly common and often fatal opportunistic
      fungal infection in patients with hematologic malignancies. Prolonged and
      profound neutropenia remains a key risk factor for the development of invasive
      aspergillosis. However, qualitative deficiencies in host immune responses
      resulting from prolonged corticosteroid therapy, graft-versus-host disease, and
      cytomegalovirus infection are important risk factors for the recurrence and
      progression of Aspergillus infections after bone marrow recovery. Early diagnosis
      of invasive aspergillosis remains a challenge, and few tools are available for
      monitoring its course once the diagnosis is established. Even with the recent
      introduction of new antifungal therapies, mortality in patients with invasive
      aspergillosis remains high, and uniformly effective prophylaxis or preemptive
      therapeutic strategies are lacking. Strategies such as combination antifungal
      therapy and immunotherapy often are used as first-line treatment approaches in
      patients with documented invasive aspergillosis despite a paucity of clinical
      trial data. Recent advances in our understanding of the epidemiology,
      pathogenesis, and treatment of invasive aspergillosis in patients with
      hematologic malignancies are reviewed. The problems and controversies associated
      with defining optimal treatment strategies for invasive aspergillosis in this
      heavily immunocompromised population are highlighted.

PMID- 14695040
TI  - A structured review of the relationship between microalbuminuria and
      cardiovascular events in patients with diabetes mellitus and hypertension.
AB  - STUDY OBJECTIVE: To quantify the relative risk of cardiovascular events
      associated with microalbuminuria in patients with both diabetes mellitus and
      hypertension. DESIGN: A structured literature search from January 1990-December
      2002 using MEDLINE, IPA, and CINAHL. MEASUREMENTS AND MAIN RESULTS: We identified
      original studies that reported the presence or absence of microalbuminuria and
      estimates of risk associated with cardiovascular events in patients with both
      diabetes and hypertension. Abstracted information consisted of study design,
      patient demographics and risk factors, treatment regimens, and outcome variables.
      Point estimates and confidence intervals for relative risk were calculated from
      available data. Of 651 citations identified and reviewed based on title and
      abstract, 72 were selected for full review. Seven met the inclusion criteria.
      Because of lack of homogeneity among studies, the results were not conducive to
      pooling. Cardiovascular end points associated with the presence of
      microalbuminuria in these studies were all-cause mortality, cardiovascular
      mortality, and composite cardiovascular morbidity. The relative risk of
      cardiovascular end points associated with the presence of microalbuminuria ranged
      from 1.6 (95% confidence interval [CI] 1.2-2.2) to 7.9 (95% CI 2.5-25.3).
      CONCLUSION: From the limited information available, the risk of cardiovascular
      events and mortality is estimated to be 2-8 times higher when microalbuminuria is
      present in patients with diabetes and hypertension. Point estimates in relative
      risk of cardiovascular morbidity and mortality in patients with diabetes and
      hypertension were generally higher compared with studies estimating risk in those
      with only diabetes. Studies that examine the relationship between
      microalbuminuria (scaled as a continuous or ordinal variable) and cardiovascular
      events are necessary to clarify potential benefits of pharmacotherapies that
      reduce levels of urinary albumin.

PMID- 14695041
TI  - Fenoldopam and N-acetylcysteine for the prevention of radiographic contrast
      material-induced nephropathy: a review.
AB  - Radiographic contrast material-induced nephropathy (RCIN) is the third most
      common cause of hospital-acquired renal insufficiency and has been associated
      with an increase in patient mortality. Many strategies to prevent RCIN have been
      explored unsuccessfully. The standard of care remains hydration with 0.45% sodium
      chloride before and after administration of contrast material. Recently, N
      acetylcysteine and fenoldopam have been studied to determine their efficacy in
      preventing RCIN. Of seven prospective studies using various dosing regimens of N
      acetylcysteine, four revealed beneficial results. Although some discrepancies
      exist, the data strongly suggest that N-acetylcysteine has a role in patients at
      risk for the development of RCIN. The data for fenoldopam are more limited, with
      only one retrospective study showing benefit. Additional prospective data are
      required to determine if fenoldopam has a role in the prevention of RCIN.

PMID- 14695042
TI  - Optimizing antibiotic use in hospitals: the role of population-based antibiotic
      surveillance in limiting antibiotic resistance. Insights from the society of
      infectious diseases pharmacists.
AB  - To minimize antibiotic resistance, pharmacists increasingly are becoming involved
      in antibiotic surveillance, formulation of antibiotic use policies, and day-to
      day control of problematic antibiotic use. Population-based antibiotic
      surveillance has become common with the proliferation of electronic databases.
      The most widely applied measure of antibiotic consumption is the defined daily
      dose/1000 patient days. Most studies correlating antibiotic consumption with
      resistance have focused on antibiogram-related end points; antibiogram data
      generally reflect institutional nosocomial infection patterns. Most study designs
      have been derived from traditional epidemiology such as case-control with
      regression modeling or simple linear regression; however, these methods have
      limitations. Several experimental designs show promise. Many historical-control
      studies, including a multicentered study, suggest that population-based
      antibiotic surveillance and policy intervention can decrease antibiotic
      resistance in hospitals. Further research on the relationships among antibiotic
      surveillance, structured antibiotic policy interventions, and other
      microbiologic, patient-oriented, and economic end points is needed.

PMID- 14695043
TI  - Evaluating the impact of pharmacists in mental health: a systematic review.
AB  - Efforts to improve the outcomes of patients with mental illness often have
      involved incorporating the skills of a variety of health care professionals into
      collaborative care models. For over 30 years, clinical pharmacists have
      contributed to these care models in capacities ranging from educator to
      consultant to provider. This systematic review evaluates the quantity and quality
      of medical literature examining the impact of pharmacists in mental health from
      1972-2003. Although we identified approximately 35 publications describing the
      roles of clinical pharmacists in this regard, only 16 were of sufficient
      scientific rigor to permit evaluation and comparison. The 16 studies were divided
      equally between inpatient and outpatient settings and were conducted in a variety
      of health care organizations (e.g., Veterans Administration, health maintenance
      organizations, community mental health clinics, and nursing homes). Nine of the
      studies examined the role of pharmacists in providing treatment recommendations
      and patient education, five featured pharmacists as providers (with prescriptive
      authority), and the remaining two described the impact pharmacists have in
      delivering education to the psychiatric staff. Six of the 16 studies were
      prospective, but only three of these incorporated a randomization procedure for
      patients or facilities. Collectively, the results of the 16 studies were
      positive, demonstrating improvements in outcomes, prescribing practices, patient
      satisfaction, and resource use. Unfortunately, most of the investigations were
      small, and significant limitations in study design limited further comparison.
      Given the long history and anecdotal success of pharmacists in mental health care
      settings, additional multicenter cost-effectiveness trials are warranted to
      further support the role of the psychiatric pharmacist.

PMID- 14695044
TI  - Acute myocardial infarction induced by ephedrine alkaloids.
AB  - A 45-year-old woman was hospitalized to rule out acute myocardial infarction
      after coming to the emergency department with a complaint of substernal chest
      pressure. Her initial electrocardiogram indicated normal sinus rhythm with T-wave
      inversion and nonspecific ST changes suggestive of possible ischemia. She had no
      medical problems and took no prescription drugs. Further evaluation revealed that
      for approximately 4 years she had been taking Metabolife 356 preparations--a
      source of ephedrine alkaloids--for weight loss, and that she was at low risk for
      atherosclerotic coronary artery disease. Due to elevated cardiac markers, cardiac
      catheterization was performed, which revealed no atherosclerosis in the coronary
      arteries. The patient's acute myocardial infarction was attributed to coronary
      artery vasospasm induced by ephedrine alkaloids. Clinicians should be aware of
      the growing evidence that supports life-threatening cardiovascular toxicities
      associated with these substances.

PMID- 14695045
TI  - Ethylene glycol intoxication: case report and pharmacokinetic perspectives.
AB  - A 42-year-old man was brought to the emergency department with ethylene glycol
      intoxication. He was hemodynamically stable and had normal renal function. His
      serum ethylene glycol concentration was 284 mg/dl approximately 1 hour after
      ethylene glycol consumption. The patient was treated with fomepizole and forced
      diuresis. Elimination of ethylene glycol in this patient followed first-order
      pharmacokinetics. Elimination pharmacokinetics in this patient were compared with
      that in a patient who received fomepizole and hemodialysis. Fomepizole
      monotherapy can be given in patients without renal failure or metabolic acidosis
      even with serum ethylene glycol concentrations greater than 50 mg/dl. However,
      cost estimates based on this case suggest that if the patient is treated
      adequately with a single hemodialysis session and 24-hour hospitalization, then
      fomepizole monotherapy may be more expensive than the combination regimen of
      fomepizole and hemodialysis.

PMID- 14695046
TI  - Late-onset drug fever associated with minocycline: case report and review of the
      literature.
AB  - A 15-year-old Caucasian boy experienced severe fever, fatigue, and a 40-lb weight
      loss after 2 years of minocycline therapy. A workup for infectious causes was
      negative. One week after minocycline discontinuation, the patient reported that
      his fever had resolved. Two months later, he reported full resolution of
      symptoms, weight gain, and a return to normal activity. An objective causality
      assessment indicated that his illness probably was caused by minocycline, which
      is considered a safe drug; however, it has been associated with rare serious
      adverse effects. This patient's presentation of fever was noteworthy not only
      because minocycline is a rare cause of drug fever, but also because of the
      delayed onset. Clinicians should be aware that minocycline may cause severe fever
      and illness even after an extended period of drug exposure.

PMID- 14695047
TI  - Cognitive impairment associated with atorvastatin and simvastatin.
AB  - Clinical guidelines for cholesterol testing and management have been updated
      recently. With the evolving recognition of benefits and intensified
      recommendations for cholesterol management, many more patients will require
      cholesterol-lowering drugs. All the statins share similar adverse-effect
      profiles, with a low overall frequency of undesirable effects. Emerging data
      associate statins with a decreased risk of Alzheimer's disease; however, we
      report two women who experienced significant cognitive impairment temporally
      related to statin therapy. One woman took atorvastatin, and the other first took
      atorvastatin, then was rechallenged with simvastatin. Clinicians should be aware
      of cognitive impairment and dementia as potential adverse effects associated with
      statin therapy.

PMID- 14695048
TI  - Fatality related to a 30-g venlafaxine overdose.
AB  - A 30-g venlafaxine overdose resulted in death for a 39-year-old woman whose 43
      day clinical course was highlighted by refractory hypotension and the resulting
      complications of bowel ischemia and perforation. Her venlafaxine and O
      desmethylvenlafaxine levels, analyzed by high-performance liquid chromatography
      one day after ingestion, were 21.82 mg/L (therapeutic range 0.1-0.5 mg/L) and
      3.33 mg/L (0.2-0.4 mg/L), respectively. These levels remained elevated for over 7
      days. Postulated explanations for these extended elevated levels were saturation
      of drug metabolism, decreased drug metabolism, and existence of a genetic
      polymorphism. Our patient's venlafaxine overdose produced a wide variety of
      clinical challenges, to include seizures, tachycardia, decreased level of
      consciousness, refractory hypotension, and bowel dysmotility. In addition, this
      case augments the growing body of literature that suggests that venlafaxine may
      be fatal in overdose situations.

PMID- 14695049
TI  - A general systems approach to suicide prevention: lessons from cardiac prevention
      and control.
AB  - The pathology of cardiac disease includes genetic, physical, biochemical,
      psychological, social, and environmental vectors. Factors contributing to suicide
      have been identified in these same areas. Survival from an acute cardiac event
      requires a systematized and multisectoral response. Communities that do not have
      systematized response capabilities to acute cardiac events have poorer survival
      outcomes. Suicide prevention and control may also be responsive to an integrated
      community response system. This paper examines the development of a community
      cardiac care model, explores potential parallels for a community suicide
      prevention and control model, and outlines a general systems theory framework for
      a suicide prevention and control system.

PMID- 14695050
TI  - Correlates of relative lethality and suicidal intent among deliberate self-harm
      patients.
AB  - Conflicting findings have been reported regarding the relationship between the
      potential lethality of acts of deliberate self-harm (DSH) and suicidal intent,
      and how each relates to patient characteristics. This study examines the
      relationship of suicidal intent of DSH to lethality, the relationship of both to
      patient characteristics, and determines if intent or lethality are risk factors
      for repetition of DSH. Potential lethality and Suicide Intent Scale (SIS) scores
      for DSH episodes were examined in a representative sample of 150 patients
      presenting to a general hospital. Follow-up interviews were completed 12 to 20
      months later. Lethality was strongly associated with high intent. Both lethality
      and intent were associated with male gender. Suicidal intent but not lethality
      was associated with the presence of psychiatric disorder and depression. Intent
      was significantly correlated with hopelessness scale score. Although intent was
      correlated with both depression and self-esteem scale scores, these correlations
      became nonsignificant when the effect of hopelessness was removed. Repetition of
      DSH during the follow-up period was related to neither lethality nor intent
      scores for the original episodes. Lethality and suicidal intent, although
      related, have somewhat different correlates. Both should be considered when
      assessing DSH patients, but their relationship to further suicidal behavior does
      not appear to be straightforward.

PMID- 14695051
TI  - Toward an empirical taxonomy of suicide ideation: a cluster analysis of the youth
      risk behavior survey.
AB  - In this study we examined adolescent risk behaviors, giving special attention to
      suicide ideation. Cluster analysis was used to classify adolescents (N = 2,730)
      on the Youth Risk Behavior Survey. Six clusters of adolescent risk behavior were
      identified. Although each risk cluster was distinct, some clusters shared
      overlapping risk behaviors. Suicide ideation was central to two clusters: the
      Silent Suicide cluster and the Multiple Risk cluster. The findings demonstrate
      that suicide ideation is both a unique risk behavior for some adolescents and
      part of a generalized risk syndrome for other adolescents. A multiple subgroup
      framework is recommended for understanding adolescent risk behaviors.

PMID- 14695052
TI  - Stable hopelessness and its predictors in a general population: a 2-year follow
      up study.
AB  - Information on hopelessness at the population level is limited, and no previous
      studies have focused on its stability in a general population. We examined the
      stability and associated factors of hopelessness in a general population sample
      of 1,389 adults. More than half of those who were hopeless at baseline remained
      hopeless on follow-up. When those with a mental disorder were excluded, the
      relative risk for stable hopelessness in unemployed men was 7.2 (95% CI 2.6
      19.9), in men with a poor financial situation it was 3.5 (95% CI 1.3-9.3), and in
      women with a poor financial situation it was 3.8 (95% CI 1.5-9.4). Awareness of
      the stability of hopelessness offers us newpossibilities in preventative and
      mental health work.

PMID- 14695053
TI  - Suicide after suicide attempt in severe depression: a long-term follow-up.
AB  - The temporal relation between completed suicide and first-ever suicide attempt
      was investigated in 58 future suicides with a primary severe
      depression/melancholia. The median survival after a first attempted suicide was
      6.7 years. Male patients with initial ratings of psychomotor retardation lived
      significantly longer after their initial attempt than those who were not
      retarded. They also had more depressive episodes compared to other male suicides
      and retarded controls. Thus a slow suicidal process in the men with a severe
      depression and psychomotor retardation is proposed. Severity, repetition, and
      method of suicide attempt did not decrease the survival time.

PMID- 14695054
TI  - Affective, behavioral, and cognitive functioning in adolescents with multiple
      suicide attempts.
AB  - The purpose of this study was to examine affective, behavioral, and cognitive
      functioning in adolescents with multiple suicide attempts. Forty-seven
      adolescents with a history of multiple suicide attempts (MA) were compared to 74
      single suicide attempters (SA) on psychiatric diagnosis, depressive symptoms,
      affect regulation, self-mutilation, alcohol use, and hopelessness. Results
      revealed that the MA group was more likely to be diagnosed with a mood disorder,
      and reported more severe depressive symptoms and anger, in comparison to the SA
      group. Behaviorally, the MA group had higher rates of disruptive behavior
      disorders and higher levels of affect dysregulation and serious self-mutilation
      than the SA group. Further, greater levels of hopelessness were reported by the
      MA than the SA group. After controlling for a mood disorder diagnosis, only
      differences in anger, affect dysregulation, and serious self-mutilation remained
      significant. Overall, results suggest that treatment with adolescent suicide
      attempters might specifically target anger and affect dysregulation to reduce
      risk for future suicidal behavior.

PMID- 14695055
TI  - Telephone counselling for adolescent suicide prevention: changes in suicidality
      and mental state from beginning to end of a counselling session.
AB  - Telephone counselling is an accessible and confidential means by which distressed
      young people can seek help. Telephone counselling services were funded under
      Australia's National Youth Suicide Prevention Strategy between 1997 and 2000. In
      this study, the effectiveness of telephone counselling for young people seeking
      help in the context of suicidal ideation or intent was evaluated in an
      investigation of calls made by suicidal young people to a telephone counselling
      service. Independent raters measured callers' suicidality and mental state at the
      beginning and end of 100 taped counselling sessions. Changes in suicidality and
      mental state were measured using a reliable rating scale developed for the study.
      Significant decreases in suicidality and significant improvement in mental state
      were found to occur during the course of counselling sessions, suggesting
      positive immediate impact. Limitations of the study with respect to longer-term
      outcomes and the relevance of the results for suicide prevention are discussed.
      Notwithstanding the study limitations, the results lend support for continuing
      development of hotline services.

PMID- 14695056
TI  - Uncovering the mystery: factors of African American suicide.
AB  - Traditionally, African Americans have registered lower rates of suicide than
      other ethnic groups. In the last 20 years this pattern has changed, particularly
      among young African Americans. To date, the research conducted regarding this
      phenomenon has been limited for a variety of reasons and previous research has
      been inconclusive in determining risk factors of African American suicide. The
      purpose of this paper is to identify risk and protective factors specific to
      African American suicide. To determine the factors, the 1993 National Mortality
      Follow-back Survey was analyzed. The risk factors identified include being under
      age 35, southern and northeastern residence, cocaine use, firearm presence in
      home, and threatening others with violence. Some of the protective factors
      associated with African American suicide include rural residence and educational
      attainment. These results provide valuable information about completed African
      American suicides in relation to Whites. Several of these factors are unique to
      African Americans.

PMID- 14695057
TI  - Discriminators of suicide thoughts and attempts among homeless veterans who abuse
      substances.
AB  - Six hundred homeless military veterans who abused substances were examined to
      determine what factors discriminate between nonsuicidal veterans, those who had
      suicidal thoughts, and persons who had attempted suicide. Several factors were
      considered based on attachment theory, including caregiver attachment, sexual
      abuse, physical abuse, resilience, self-efficacy, and self-esteem. Suicide
      attempters were discriminated from others by psychiatric comorbidity, early
      abuse, severity of substance abuse, and longevity of drug use. In contrast, the
      discriminators between nonsuicidal homeless substance abusers and others were
      elements of attachment and commitments such as marriage, employment, and
      religiosity. Some implications of the findings for intervention are discussed.

PMID- 14695058
TI  - African American and Caucasian attempters compared for suicide risk factors: a
      preliminary study.
AB  - The aim of the study was to compare African American and Caucasian substance
      dependent suicide attempters for risk factors for suicidal behavior. One hundred
      and fifty-eight African American and 95 Caucasian substance dependent patients
      who had attempted suicide were interviewed and their family history of suicidal
      behavior recorded. Patients completed the Childhood Trauma Questionnaire, the
      Eysenck Personality Questionnaire, and the Foulds Hostility and Direction of
      Hostility Questionnaire. The results revealed that there were no significant
      differences between the African American and Caucasian suicide attempters for
      marital status, age, childhood abuse, or for personality scores for neuroticism,
      extraversion, psychoticism, or hostility. However, the African American
      attempters had significantly lower childhood emotional neglect scores. Also,
      significantly more of the Caucasian attempters had a family history of suicide
      and current legal problems. Further studies seem warranted examining for
      differences between African Americans and Caucasians for risk factors for
      suicidal behavior.

PMID- 14695059
TI  - Laur's final display: suicide by fire.

PMID- 14695060
TI  - Surrogate hosts: protozoa and invertebrates as models for studying pathogen-host
      interactions.
AB  - Animal models, primary cell culture systems and permanent cell lines have
      provided important information on virulence properties of pathogenic
      microorganisms. Recently, it has been shown that some inherent limitations of
      such models can be circumvented by using non-vertebrate hosts such as
      Caenorhabditis elegans, Drosophila melanogaster and Dictyostelium discoideum.
      These new models are helpful to follow infection processes at the molecular
      level. Persuasive support comes from the fact that processes such as
      phagocytosis, cell signaling or innate immunity can be studied in these surrogate
      hosts. This review describes the establishment and application of each of the
      three aforementioned and genetically tractable hosts. In addition, we will report
      on a number of approaches that led to the identification of host cell factors
      which influence the susceptibility of the hosts to infection.

PMID- 14695061
TI  - Plague and rats, the "plague of the Philistines", and: what did our ancestors
      know about the role of rats in plague.

PMID- 14695062
TI  - Contribution of toll-like receptors 2 and 4 in an oral Yersinia enterocolitica
      mouse infection model.
AB  - A characteristic of the three human-pathogenic Yersinia spp. (the plague agent Y.
      pestis and the enteropathogenic Y. pseudotuberculosis and Y. enterocolitica) is
      the expression of the virulence (V)-antigen (LcrV). LcrV is a released
      multifunctional protein which is involved in contact-induced secretion of
      Yersinia antihost proteins and in evasion of the host innate immune response.
      Recently, we reported that recombinant LcrV signals in a CD14- and TLR2-dependent
      fashion leading to immunosuppression by interleukin-10 (IL-10) induction. The
      impact of this immunosuppressive effect for Yersinia pathogenesis was underlined
      by the observation that IL-10- and TLR2-deficient mice were found to be less
      susceptible to Y. enterocolitica infection than isogenic C57BL/6 wild-type
      animals. In the present study, we show that Y. enterocolitica leads to higher IL
      10 and lower TNF-alpha levels in spleens from infected C57BL/6 wild-type mice
      than in those from TLR2-deficient mice. By comparing Y. enterocolitica infection
      in TLR2-, TLR4-, and TLR2/TLR4-deficient mice, we found that TLR2 is more
      important in yersiniosis than TLR4. Strikingly and in contrast to the results
      obtained in TLR2-deficient mice of C57BL/6 background, TLR2-deficient mice of C3H
      genetic background were more susceptible to an oral Y. enterocolitica infection
      than wild-type C3H mice. To our knowledge, this is the first report on a
      divergent influence of a TLR-deficiency on infection outcome in mice of different
      genetic backgrounds.

PMID- 14695063
TI  - Description of a putative type I secretion system in Legionella pneumophila.
AB  - Here we describe the first putative type I secretion system of L. pneumophila.
      The lssXYZABD locus was found to be present in all L. pneumophila strains tested
      so far. The LssB and LssD proteins are homologues to the proteins of type I
      secretion systems of Vibrio cholerae and Salmonella typhi. The expression of the
      gene locus was analysed by RT-PCR. Three polycistronic transcripts could be
      identified. Comparison of the lss locus of L. pneumophila Philadelphia I with
      that of L. pneumophila Corby revealed protein identities of 97 to 99%, except for
      LssE proteins that were only 78.6% identical. Computer analysis of the amino acid
      sequence of LssE identified it as a putative signalling protein.

PMID- 14695064
TI  - Evaluation of RIDOM, MicroSeq, and Genbank services in the molecular
      identification of Nocardia species.
AB  - The molecular identification of Nocardia species, when compared to phenotypic
      identification, has two primary advantages: rapid turn-around time and improved
      accuracy. The information content in the 5'-end of the 16S ribosomal RNA gene is
      sufficient for identification of most bacterial species. An evaluation was
      performed to demonstrate the quality of results provided by two specialized
      databases (RIDOM and MicroSeq 500 versions 1.1 and 1.4.3, library version 500
      0125, respectively) and the more general GenBank database. In addition, these
      results were compared with phenotypic identifications. Partial 5'-16S rDNA
      sequences from 64 culture collection strains (DSM, CIP, JCM, and ATCC) were
      derived, in duplicate, independently in two laboratories. Furthermore, the
      sequences and the conventional identification results of 91 clinical Nocardia
      isolates were determined. With the exception of N. soli and N. cummidelens, all
      Nocardia type strains were distinguishable using 5'-16S rDNA sequencing. Assuming
      a normal distribution for the pairwise distances of all unique Nocardia sequences
      and choosing a reporting criterion of > or = 99.12% similarity for a "distinct
      species", a statistical error probability of 1.0% can be calculated. When the
      various databases were searched with the clinical isolate sequences RIDOM gave a
      perfect match in 71.4% of cases whereas MicroSeq yielded a perfect match in only
      26.4%. The GenBank service gave a 100% similarity in 59.3% but in 70.4% of these
      cases the results obtained were not exclusive for a single Nocardia species.
      Conventional methods gave a correct identification in 59 cases, although most
      recent taxonomic changes were not taken into account. The RIDOM service
      (http://www.ridom-rdna.de/) is in the process of making available a comprehensive
      and high-quality database for bacterial identification purposes and provides
      excellent results for the majority of Nocardia isolates.

PMID- 14695065
TI  - A fluorescent amplified fragment length polymorphism study of Salmonella enterica
      serovar Sofia, the major Salmonella serovar isolated from chickens in Australia.
AB  - Fluorescent amplified fragment length polymorphism (FAFLP) analysis was performed
      on 68 isolates of Salmonella enterica subsp. salamae serovar Sofia (S. Sofia).
      Fifty eight isolates were obtained over a period of approximately 15 years from a
      range of human, chicken industry and environmental sources throughout Australia.
      A further ten isolates were identified from human and poultry sources in Israel
      from 1972 to 1987. Analysis of FAFLP profiles for fragments between 50 to 500
      base pairs in length indicated distinct clusters of isolates. All but seven
      isolates clustered into four groups of >90% similarity and all isolates displayed
      at least 70% similarity with each other. No cluster could be attributed to a
      particular geographical, temporal or source-of-isolation origin. It is concluded
      that S. Sofia is genetically variable with certain clones persisting over time
      but no group appears unique to Australia.

PMID- 14695066
TI  - Chlamydia pneumoniae induces the expression of inhibitor of apoptosis 2 (c-IAP2)
      in a human monocytic cell line by an NF-kappaB-dependent pathway.
AB  - Members of the inhibitor of apoptosis protein family are important factors that
      regulate apoptotic cell death. As demonstrated both by RT-PCR and Western Blot
      analysis C. pneumoniae infection of the human monocytic cell line Mono Mac 6
      induces the expression of mRNA and protein of the cellular inhibitor of apoptosis
      2 (c-IAP2). Blocking NF-kappaB DNA-binding activity by the proteasome inhibitor
      MG-132 results in decrease of C. pneumoniae-induced c-IAP2 expression. Therefore,
      C. pneumoniae may exploit the NF-kappaB pathway to induce expression of an
      antiapoptotic host cell protein that may contribute to intracellular survival of
      the pathogen.

PMID- 14695067
TI  - Reduction in antibiotic prescribing for respiratory tract infections is needed!
AB  - In general practice, approximately 25% of consultations are related to infectious
      diseases. The emergence and spread of resistant bacteria are related to
      antibiotic use on an individual and on a community level. Antibiotic prescribing
      differs profoundly from one European country to the next, though there is no
      evidence of differences in the prevalence of infectious diseases. Most
      respiratory tract infections are self-limiting conditions, and recent evidence
      shows that antibiotics only slightly modify the course of most respiratory tract
      infections. The general practitioner should focus on patients with more severe
      symptoms who might benefit more from antibiotic treatment. In general,
      antibiotics should be prescribed for acute pneumonia. In addition, we may offer
      antibiotics to a selected group of patients with more severe symptoms of
      maxillary sinusitis, pharyngotonsillitis and acute exacerbation of chronic
      obstructive pulmonary disease/chronic bronchitis. In the diagnostic procedure,
      rapid tests of Streptococcus pyogenus and C-reactive protein may be valuable in
      carefully selected cases. Penicillins (penicillin V, amoxycillin) should be the
      first choice in most respiratory tract infections. Larger studies in general
      practice are needed to analyse the impact of antibiotic prescribing on morbidity,
      the occurrence of rare complications and spread of resistance. The greatest
      challenge will be to implement current knowledge in daily praxis.

PMID- 14695068
TI  - An observer-participant study in primary care of assessments of inability to work
      in immigrant patients with ongoing sick leave.
AB  - OBJECTIVE: To explore the factors related to doctors' assessments of incapacity
      to work (IW). MATERIAL: Two general practitioners and 49 men and 102 women aged
      20-45 years with ongoing sick leave. METHODS: The doctors saw all the patients
      jointly and discussed their emotions afterwards. Mental status, psychosocial
      stress, pain behaviour, tender structures, mobility and self-rated inability to
      work were assessed. Finally, the doctors separately rated the degree (0-100%) of
      reduced capacity for vocational work (DRCW). The inter-rater agreement was
      measured by kappa statistics. Prevalence odds ratios (OR) with 95% confidence
      intervals (95% CI) for IW (75-100% DRCW) were calculated by logistic regression.
      RESULTS: The patients were immigrants working in service. All reported pain,
      53.7% had much psychosocial stress, 74.8% said they were unable to work and 22.5%
      were depressed. We were often touched by their life stories. The women had many
      tender-structure locations and many men had restricted mobility. Two-thirds
      (67.5%) had pain behaviour. The kappa value on the DRCW was 0.73. A third of the
      men (38.8%) and 26.5% of the women were assessed as having IW. The raters
      disagreed only in a few cases. Depressed men or men with pain behaviour had high
      ORs for IW (OR 12.8, 95% CI 3.3-68.5 and OR 5.6, 95% CI 1.5-21.1, respectively)
      as did women with self-rated inability to work (OR 7.0; 95% CI 1.6-32.0).
      CONCLUSIONS: Factors not clearly related to function had determined doctors'
      assessments of IW.

PMID- 14695069
TI  - Challenging heteronormativity in the consultation: a focus group study among
      general practitioners.
AB  - OBJECTIVE: To reflect on and further understand mechanisms of heteronormativity
      in the consultation, with special focus on the relative invisibility of lesbian
      women. DESIGN: Tape-recorded focus group interviews transcribed verbatim and
      analysed using qualitative methods. SETTING: General practitioners (GPs) from the
      city of Goteborg, Sweden, who had formerly answered a postal questionnaire about
      lesbian women in the consultation, were invited to take part in subsequent focus
      groups. SUBJECTS: Ten GPs from the questionnaire who accepted the invitation and
      volunteered to participate in focus groups. MAIN OUTCOME MEASURES: A discourse
      analytical approach using interaction regarding consensus and disagreement
      between informants in creating major and minor themes. RESULTS: Consultation
      skills were forwarded as a major tool in receiving optimal information from
      patients. However, traditional concepts of family and sexuality restricted
      information and hampered an accepting attitude. Bringing up issues of sexual
      identity/orientation was left to the lesbian patient and strongly related to her
      reason for attending. CONCLUSION: Consultation skills are a useful but not
      sufficient means of making lesbian women visible in the doctor-patient
      relationship. Doctors also need to transcend traditional concepts of family and
      sexuality and reflect on what is a relevant issue from the patient's perspective.

PMID- 14695070
TI  - Introduction of the patient-list system in general practice. Changes in Norwegian
      physicians' perception of their gatekeeper role.
AB  - OBJECTIVE: To explore whether the patient-list system, recently introduced in
      general practice, has influenced general practitioners' (GPs') self-perception as
      gatekeepers. DESIGN: Structured focus group interviews with GPs and a short self
      administered questionnaire. SETTING: Primary care within the public health care
      system in Norway. Group interviews were conducted 6 months to 1 year after the
      patient-list system was introduced in June, 2001. SUBJECTS: 81 GPs attending
      tutorial groups or specialists' continuous education groups. OUTCOME MEASURES:
      GPs' experience with the reform as stated in 11 group discussions, recorded,
      transcribed and systematically analysed through coding and extracting of the
      informants' statements. The questionnaire provided background information about
      each participant. RESULTS: The doctors generally perceived themselves as less
      concerned with the gatekeeper role under the new system. They felt it more
      important to provide better services and keep patients satisfied. The
      practitioners explained this shift using three contextual factors: increased and
      more visible competition, higher expectations from the patients and more
      responsibility assigned to the GP. CONCLUSION: GPs in Norway have experienced a
      shift in power in the physician-patient relationship favouring the patient. The
      GP's consciousness of the gatekeeper role has diminished. We question whether the
      new system lessens the incentive to consider resource use in decision-making.

PMID- 14695071
TI  - Are there any clinical characteristics of depression in elderly people that could
      be useful for case finding in general practice?
AB  - OBJECTIVES: The aim of this study was to identify clinical characteristics of
      depression in elderly people that could be useful for case finding in general
      practice. DESIGN: A cross-sectional study of clinical characteristics through
      review of medical records. SETTING: Herrhagen health centre, Karlstad, Sweden.
      SUBJECTS: Seventy-one persons with a high depressive score in a screening of
      depressive symptoms and an age-matched and sex-matched control group of 138
      persons with a low depressive score. RESULTS: The high depressive score group had
      an increased relative risk for "mental health problems" (RR 3.4; CI 95% 1.7-7.2),
      "many contacts with the health care centre" (> or = 14/3 years) (RR 2.9; CI 95%
      1.4-6.1), and prescriptions of benzodiazepines (RR 1.7; CI 95% 1.0-2.9). Two
      thirds of those in the high depressive score group had at least one of these
      characteristics. However, three-quarters of those with any of these
      characteristics had a low depressive score. In our population of elderly people
      with an estimated prevalence of 10.2% the positive predictive value would be 21%
      and the negative predictive value 95%. CONCLUSION: General practitioners should
      suspect a possible depressive disorder in elderly patients with mental health
      problems, with frequent contacts with the health centre or with prescriptions of
      benzodiazepines. Despite the high occurrences of these prominent clinical
      characteristics in the high-score group, they did not unfortunately have
      sufficient discriminatory power to be useful for case finding.

PMID- 14695072
TI  - Randomised controlled trial of the effectiveness of feedback in improving test
      ordering in general practice.
AB  - OBJECTIVE: To assess the effectiveness of feedback on the number of pathology
      tests ordered by general practices. DESIGN: Randomised controlled trial. SETTING:
      General practices in two primary care groups in Leicestershire, UK. SUBJECTS: 58
      general practitioners in 17 practices received guidelines then feedback at 3
      month intervals for 1 year about the numbers of thyroid function, rheumatoid
      factor tests and urine cultures they ordered, and 38 general practitioners in 16
      practices received guidelines then feedback about lipid and plasma viscosity
      tests. MAIN OUTCOME MEASURES: Numbers of tests requested per thousand patients
      registered with each practice. RESULTS; There were no changes in the numbers of
      tests per thousand requested in either of the study groups for any of the tests.
      CONCLUSIONS: Feedback did not have an influence on test ordering by general
      practitioners in this study. More intensive strategies may be required to change
      the use of laboratory tests.

PMID- 14695073
TI  - "Alarm symptoms" in dyspepsia. How does the general practitioner investigate?
AB  - OBJECTIVE: Alarm symptoms are present in 10% of patients consulting a general
      practitioner (GP) because of dyspepsia. The options for the GP are: perform "own"
      investigation, refer to a specialist or secondary care, or maintain watchful
      waiting. DESIGN: Postal questionnaire to GPs obtaining information from the
      records of patients who had consulted earlier owing to dyspepsia and reported one
      or more alarm symptoms at the consultation. SETTING: 92 general practices
      throughout Denmark. SUBJECTS: In 7240 consecutive consultations in 1991-1992 a
      total of 749 patients reported 881 alarm symptoms. Follow-up data 3 years later
      were obtained from 81%. MAIN OUTCOME MEASURES: The management of alarm symptoms
      by GPs: "own" investigation, referral to specialist, or expectance; procedures
      used in "own" investigations, patient characteristics related to such decisions,
      and gastrointestinal diseases diagnosed by this management. RESULTS: 67% of the
      patients with alarm symptoms were investigated promptly (8% by referral to
      specialists) and 33% were left uninvestigated, with great variations between
      alarm symptoms. The single most preferred GP investigation was endoscopy. A
      gastrointestinal diagnosis was obtained in 35% of the patients; 3% of these were
      malignancies while 9% were peptic ulcers. CONCLUSION: The decision on whether and
      how to investigate alarm symptoms is complex and relates to specific symptom,
      type of dyspepsia, age, gender and dwelling of the patient.

PMID- 14695074
TI  - Factors affecting the efficacy of starting insulin treatment in Type 2 diabetic
      patients. A retrospective evaluation.
AB  - OBJECTIVE: To assess the efficacy and practices of insulin treatment in Type 2
      diabetes mellitus in primary health care. SETTING: Primary health care in
      southwest Finland (population 250,000). DESIGN: Cases in the target area with
      insulin treatment initiated in 1991-1997 were identified and the patient records
      were analysed retrospectively for up to 5 years from treatment. PATIENTS: A total
      of 883 patients with Type 2 diabetes (aged 40-91 years) were identified. MAIN
      OUTCOME MEASURES: HbA1c and body weight. RESULTS: HbA1c declined by 2.0
      percentage points from 10.0% to 8.0% (p < 0.001) at 12 months from the initiation
      of insulin, irrespective of age. The decrease was smaller in obese patients (BMI
      > 34 kg/m2). A slightly better glycaemic control was achieved when the treatment
      was initiated by a specialist rather than by a general practitioner. The
      improvement in HbA1c was essentially unchanged at 4 years. The decrease in HbA1c
      was largely independent of the type of the insulin regimen (insulin alone,
      combined insulin and oral therapy). The daily insulin dose increased markedly and
      the proportion of patients on combination therapy decreased from 57% to 38% at 4
      years. The mean body weight of the patients increased (3.7 kg at 12 months, 5.7
      kg at 4 years). The weight increase was highest in patients treated with insulin
      alone. CONCLUSIONS: Introducing insulin therapy in poorly controlled Type 2
      diabetic patients results in a marked decrease in HbA1c. Insulin therapy can be
      initiated in all age groups with equal results. Insulin treatment can be
      initiated and improved metabolic control maintained in primary health care.

PMID- 14695075
TI  - Smokers in Vasterbotten County, Sweden. What contributes to increased
      cardiovascular risk among heavy smokers?
AB  - OBJECTIVE: To analyse risk factor levels and risk factor patterns among heavy
      smokers compared to never smokers. DESIGN: An incident case-referent study.
      SETTING: The study was nested within the Vasterbotten Intervention Programme
      (VIP). SUBJECTS: 286 people (62 women and 224 men) claimed to be heavy smokers,
      i.e. smoked 25 cigarettes or more per day. For each of them, two referents (who
      reported never to have been smokers) were matched on age and gender (572
      referents). MAIN OUTCOME MEASURES: Differences in biomedical variables and social
      and lifestyle factors were confirmed. RESULTS: S-cholesterol, s-triglycerides,
      fasting blood glucose, body weight and body mass index were all significantly
      elevated among the heavy smokers. Some gender differences were also found. Social
      and lifestyle factors differed significantly between heavy smokers and never
      smokers, but without gender differences. CONCLUSIONS: Heavy smokers carry a risk
      factor pattern corresponding to an increased risk of developing cardiovascular
      disease. Unfavourable changes in serum lipids and in glucose metabolism can
      exacerbate other deleterious effects of tobacco smoke on the cardiovascular
      system. Obviously, heavy smokers and never smokers differ not only in regard to
      biomedical variables but also to lifestyle and social health determinants. These
      are important factors to consider in public health efforts aimed at reducing the
      increased risk for cardiovascular diseases among smokers.

PMID- 14695076
TI  - Participation bias in longitudinal studies: experience from the Population Study
      of Women in Gothenburg, Sweden.
AB  - OBJECTIVE: To describe a cohort study of women receiving a series of
      comprehensive health examinations over 32 years. DESIGN: Longitudinal population
      study based on a randomised sample of the female population from defined age
      cohorts. SETTING: City of Goteborg, Sweden. SUBJECTS: Subjects were 38, 46, 50,
      54 or 60 years old at the start of the study in 1968. Re-examinations were
      performed in 1974, 1982 and 1992. Non-participants in the most recent
      examination, initiated in 2000, were offered home visits. MAIN OUTCOME MEASURES:
      Participation, anthropometric and blood pressure changes. RESULTS: At the end of
      the 32-year follow-up, 64% of the original participants were alive, and low
      participation among survivors was a problem. An acceptable participation rate
      (71% of those alive) was obtained after home visits were offered. Surviving non
      participants already had elevated cardiovascular risk factors at onset of the
      study in 1968, along with lower educational level and lower socioeconomic status.
      Home visited subjects were similar to non-participants with regard to
      anthropometry and blood pressure, but did not differ from participants with
      regard to social indicators. Thirty-two-year longitudinal data demonstrate clear
      ageing effects for several important variables, which should, however, be
      considered in the context of documented differences with non-participants at the
      baseline examination. CONCLUSIONS: Longitudinal studies in elderly populations
      provide important data on changes during the ageing process. However,
      participation rates decline for a number of reasons and generalisations should be
      made with care. Moreover, including home visits in the protocol can both increase
      participation and reduce participation bias in elderly cohorts.

PMID- 14695077
TI  - Lifestyle changes after a health dialogue. Results from the Live for Life health
      promotion programme.
AB  - OBJECTIVE: To evaluate the effect of a health dialogue on lifestyle habits, and
      to relate the lifestyle changes to changes of biological risk markers for
      ischaemic heart disease. DESIGN: Cross-sectional study, intervention and follow
      up. SETTING: The community of Habo, population 9500, located in Skaraborg,
      Sweden. PATIENTS: All 35-year-old inhabitants in Habo were invited to a health
      examination during a study period between 1989 and 1992. A community intervention
      programme was combined with a health examination consisting of a health dialogue
      with a specially trained nurse and use of a "health curve" as an educational
      tool. The effect of the health examination was examined by comparing baseline
      characteristics of participants in 1989-1992 with their follow-up data in 1993.
      RESULTS: Participants in the health dialogue who were re-examined reported
      lifestyle improvements including less smoking, decreased dietary fat intake and
      increased physical activity. Those who reported improved dietary intake and
      increased physical activity improved their biological risk markers
      correspondingly (body mass index, waist to hip ratio, serum cholesterol
      concentration). CONCLUSIONS: The combination of a community and an individually
      based health programme can be effective with respect to lifestyle variables and,
      in those improving their lifestyle, in biological risk markers.

PMID- 14695078
TI  - Taxonomy: get it right or leave it alone.

PMID- 14695079
TI  - Enzootic transmission of Babesia divergens among cottontail rabbits on Nantucket
      Island, Massachusetts.
AB  - Specific ticks seem to locally serve as vector for characteristic microbial
      assemblages (guilds) comprising spirochetes, piroplasms, ehrlichiae, and
      arboviruses. Borrelia andersoni and Anaplasma phagocytophilum are intensely
      transmitted between cottontail rabbits. To test the hypothesis that a piroplasm
      may also be maintained in rabbits, we sampled these hosts from Nantucket Island,
      Massachusetts and tested their blood and tissues by a polymerase chain reaction
      for evidence of infection. Surprisingly, the agent of bovine redwater and of
      European human babesiosis, Babesia divergens, was detected in 16% of the rabbits
      sampled during 1998-2002 (> 99% sequence similarity in the 18S ribosomal DNA).
      The vector of B. divergens on Nantucket appears to be Ixodes dentatus, a rabbit-
      and bird-feeding tick that may feed on humans. Although the risk of human
      infection appears to be minimal, an autochthonously acquired Kentucky case due to
      this rabbit agent was recently reported. Physicians should entertain the
      diagnosis of babesiosis due to B. divergens for severe hemolytic febrile
      syndromes in American patients exposed to sites where rabbits are common.

PMID- 14695080
TI  - Diagnosis of tuberculosis lymphadenitis using a polymerase chain reaction on
      peripheral blood mononuclear cells.
AB  - Providing prompt and precise laboratory confirmation of a clinical diagnosis of
      tuberculous lymphadenitis is difficult given the paucibacillary nature of lymph
      node specimens. In this study carried out in Karachi, Pakistan, a polymerase
      chain reaction (PCR) assay aimed at detecting Mycobacterium tuberculosis DNA in
      peripheral blood mononuclear cells (PBMC-PCR) was standardized and compared with
      standard M. tuberculosis diagnostic techniques or a lymph node PCR (LN-PCR) for
      the diagnosis of tuberculosis lymphadenitis. Thirty-seven (77%) specimens from 48
      patients with clinical or diagnosis of tuberculosis lymphadenitis were positive
      by cytology [17/48 (35%) with no acid fast bacilli (AFB) (suggestive), and 20/48
      (42%) with AFB (positive) in direct smears], 30 (63%) by PBMC-PCR, 16 (33%) by LN
      PCR, and 13 (27%) by culture. All controls were negative, with the exception of
      one false-positive LN-PCR. These data suggest the PBMC-PCR may be helpful in the
      diagnosis of tuberculous lymphadenitis.

PMID- 14695081
TI  - Chronic cerebral paragonimiasis combined with aneurysmal subarachnoid hemorrhage.
AB  - A 67-year-old Korean woman attended our hospital complaining of a severe
      headache. A brain computed tomography scan showed conglomerated, high-density,
      calcified nodules in the left temporo-occipito-parietal area and high-density
      subarachnoid hemorrhage in the basal cisterns. Magnetic resonance imaging of the
      brain shows multiple conglomerated iso- or low-signal intensity round nodules
      with peripheral rim enhancement. She underwent craniotomies to clip the aneurysm
      and remove the calcified masses. Paragonimus westermani eggs were identified in
      the calcified necrotic lesions. Results of parasitic examinations on the sputum
      and an enzyme-linked immunosorbent assay for P. westermani were all negative. The
      patient presented with headache and dizziness that had occurred for more than 30
      years. She had not eaten freshwater crayfish or crabs. However, she had sometimes
      prepared raw crabs for several decades. Overall, this case was diagnosed as
      chronic cerebral paragonimiasis, in which she may have been infected through the
      contamination of utensils during the preparation of the second intermediate
      hosts, combined with a cerebral hemorrhage.

PMID- 14695082
TI  - Short report: a disseminated infection of Leishmania mexicana in an eastern
      woodrat, Neotoma floridana, collected in Texas.
AB  - An eastern woodrat (Neotoma floridana) collected in January 2001 near Bedias,
      Grimes County, Texas, had extensive lesions of both ears and swollen feet.
      Impression smears and histologic sections demonstrated the presence of Leishmania
      in both ears and the one foot that was screened. Polymerase chain reaction
      screening using species-specific primers detected parasites in both ears and all
      four feet and indicated the parasites were L. mexicana. The detection of L.
      mexicana in N. floridana represents a new host record in a new ecologic region
      and may help explain a human infection acquired outside the previously-known
      range of the disease. Given the geographic distribution of N. floridana and the
      two other species of Neotoma found naturally infected, enzootic foci of
      Leishmania could be present over much of the southern United States.

PMID- 14695083
TI  - The transmission dynamics of canine American cutaneous leishmaniasis in Huanuco,
      Peru.
AB  - The epidemiology of canine American cutaneous leishmaniasis (ACL) due to
      Leishmania (Viannia) spp. was investigated in Huanuco, Peru to 1) describe the
      natural course of canine L. (Viannia) infections and 2) assess the role of
      domestic dogs as ACL reservoir hosts. Over a three-year period 1,022 dogs were
      surveyed, with cumulative village L. (Viannia) prevalence being 26% (range = 0
      100%). The incidence of L. (Viannia) was estimated to be 0.285 dogs/year (95%
      confidence interval [CI] = 0.160-0.410) using cross-sectional data and 0.291
      dogs/year (95% CI = 0.195-0.387) using data from 108 dogs that were surveyed
      prospectively. The recovery rate was estimated to be 0.456 dogs/year (95% CI =
      0.050-0.862) and 0.520 dogs/year (95% CI = 0.302-0.738), respectively. Using
      those findings, the basic reproduction number was estimated to be R0
      approximately to 1.9; if dogs were the principal ACL reservoirs, the mean yearly
      effort (i.e., coverage or elimination) of a dog control intervention (e.g.,
      collaring, culling, or vaccination) to ensure the elimination of L. (Viannia)
      spp. transmission would be as low as 47%.

PMID- 14695084
TI  - Short report: requirement of b cells for delayed type hypersensitivity-like
      pathology after secondary infection with Leishmania major in resistant C57BL/6
      mice.
AB  - B cell-deficient C57B1/6 (microMT) mice were resistant to Leishmania major after
      both primary and secondary parasite challenge. However, unlike in wild-type mice,
      secondary infection in microMT mice was not accompanied by a marked delayed type
      hypersensitivity-like response, and interferon-gamma (IFN-gamma) levels were
      approximately half of those in wild-type mice. These results suggest that B cells
      are involved in IFN-gamma production and the pathology of secondary infection.

PMID- 14695085
TI  - Genetic relationships among some species groups within the genus Lutzomyia
      (Diptera: Psychodidae).
AB  - Molecular data on Lutzomyia are very scarce, despite the fact that this genus
      includes all the species involved in the transmission of leishmaniasis in
      America. We examine the genetic relationships among eight morphologic groups
      within the Lutzomyia genus and two Brumptomyia species, using nine enzyme loci
      and the last 285 basepairs of the mitochondrial cytochrome b gene. The structure
      of the genetic variation among the species analyzed indicated a closer genetic
      relationship among members of a morphologic group than between members of
      different groups. The lower levels of variation recorded among these groups
      compared with that between Brumptomyia and Lutzomyia suggest a subgeneric status
      for all of these groups, including Psychodopygus. A maximum likelihood tree for
      the allozyme data and a neighbor-joining consensus tree for the mitochondrial DNA
      sequences showed a general agreement with morphologic groups, with only minor
      differences. Nyssomyia, Verrucarum and Micropygomyia formed separate monophyletic
      groups. Lutzomyia could not be separated from Psathyromyia, and both Migonei
      species, L. dubitans and L. migonei, grouped in different clades according to the
      host species they are found on.

PMID- 14695086
TI  - Characteristics of the spatial pattern of the dengue vector, Aedes aegypti, in
      Iquitos, Peru.
AB  - We determine the spatial pattern of Aedes aegypti and the containers in which
      they develop in two neighborhoods of the Amazonian city of Iquitos, Peru. Four
      variables were examined: adult Ae. aegypti, pupae, containers positive for larvae
      or pupae, and all water-holding containers. Adults clustered strongly within
      houses and weakly to a distance of 30 meters beyond the household; clustering was
      not detected beyond 10 meters for positive containers or pupae. Over short
      periods of time restricted flight range and frequent blood-feeding behavior of
      Ae. aegypti appear to be underlying factors in the clustering patterns of human
      dengue infections. Permanent, consistently infested containers (key premises)
      were not major producers of Ae. aegypti, indicating that larvaciding strategies
      by themselves may be less effective than reduction of mosquito development sites
      by source reduction and education campaigns. We conclude that entomologic risk of
      human dengue infection should be assessed at the household level at frequent time
      intervals.

PMID- 14695087
TI  - Association of virulence factor-positive and -negative enteroaggregative
      Escherichia coli and occurrence of clinical illness in travelers from the United
      States to Mexico.
AB  - The objective of the study was to determine if the presence or absence of
      virulence factor-positive and -negative enteroaggregative Escherichia coli (EAEC)
      determined the occurrence of illness or sub-clinical EAEC infection in travelers
      from the United States to Mexico. Sixty-five newly arrived college students from
      the United States submitted weekly stool samples for a four-week period of time.
      Among EAEC-infected subjects, diarrhea occurred in those with a defined virulence
      factor with the following frequency: aggA, 5 of 15 (33%); aggR, 3 of 11 (27%);
      aafA, 3 of 8 (38%); and aspU, 1 of 6 (17%). Twenty-two of 31 students (71%) had
      two or more EAEC infections. After the initial EAEC infection, only 4 (11%) of 31
      students had a subsequent symptomatic EAEC infection. Our study suggests that
      clinical illness by EAEC is not explained by presence of a defined EAEC virulence
      factors, and we provide suggestive evidence that EAEC infection protects against
      future symptomatic infection.

PMID- 14695088
TI  - Economic and social impacts of La Crosse encephalitis in western North Carolina.
AB  - La Crosse encephalitis (LACE), a human illness caused by a mosquito-transmitted
      virus, is endemic in western North Carolina. To assess the economic and social
      impacts of the illness, 25 serologically confirmed LACE case patients and/or
      families were interviewed to obtain information on the economic costs and social
      burden of the disease. The total direct and indirect medical costs associated
      with LACE over 89.6 life years accumulated from the onset of illness to the date
      of interview for 24 patients with frank encephalitis totaled dollar 791,374
      (range = dollar 7,521-175,586), with a mean +/- SD per patient cost of dollar
      32,974 +/- dollar 34,793. The projected cost of a case with lifelong neurologic
      sequelae ranged from dollar 48,775 to dollar 3,090,798 (n = 5). For the 25 LACE
      patients, 55.15 (54.83%) of the 100.59 cumulative life years (CLYs) were impaired
      to some degree. Disability adjusted life years (DALYs) were calculated to measure
      the productive life years lost to LACE. Approximately 13.00 DALYs were
      accumulated over 100.59 CLYs of study. Projected DALYs for case patients (n = 5)
      with lifelong neurologic sequelae ranged from 12.90 to 72.37 DALYs. An Impact of
      La Crosse Encephalitis Survey (ILCES) was used to measure the social impact of
      LACE over time for case patients and their families. The ILCES scores
      demonstrated that the majority of the social burden of the illness is borne by
      the five patients with lifelong neurologic sequelae. The socioeconomic burden
      resulting from LACE is substantial, which highlights the importance of the
      illness in western North Carolina, as well as the need for active surveillance,
      reporting, and prevention programs for the infection.

PMID- 14695089
TI  - Occurrence of Orientia tsutsugamushi in small mammals from Thailand.
AB  - Extensive sampling of small mammals was conducted in eight provinces of Thailand
      between September 9, 1992 and April 29, 2001. A total of 3,498 specimens
      representing 22 species were collected. Eighty-eight percent (3,089 of 3,498) of
      the animals were collected from a region in Chiangrai Province, which is commonly
      recognized as endemic for human scrub typhus. Blood and tissue samples from each
      animal were tested for the presence of Orientia tsutsugamushi, the etiologic
      agent of scrub typhus. The predominant species collected were Rattus rattus (53%,
      n = 1,863), R. losea (18%, n = 638), Bandicota indica (16%, n = 564), and R.
      exulans (4%, n = 146). Orientia tsutsugamushi was detected in 10 of the 22
      species of mammals that included R. bukit (25% infected, 1 of 4), R. rattus (23%,
      419 of 1,855), R. argentiventer (22%, 5 of 23), R. berdmorei (22%, 2 of 9), R.
      losea (13%, 82 of 638), B. indica (9%, 52 of 564), R. koratensis (8%, 1 of 12),
      B. savilei (3%, 1 of 30), R. exulans (1%, 2 of 146), and Tupaia glis (2%, 1 of
      49). Infected animals were found in Chiangrai (18% infected, 563 of 3,084),
      Bangkok (11%, 1 of 9), Sukothai (3%, 1 of 30), and Nonthaburi (1%, 1 of 69)
      Provinces. The implications towards scrub typhus maintenance and transmission are
      discussed.

PMID- 14695090
TI  - A new serum hydatid antigen detection test for diagnosis of cystic
      echinococcosis.
AB  - Cystic echinococcosis (CE) is a major public health problem with a worldwide
      distribution in both humans and animals. Diagnosis of this disease by simple and
      rapid immunoassays is a priority. The objective of the present study was to
      standardize and evaluate the latex agglutination test (LAT) as a simple test for
      the detection of circulating hydatid antigen in serum. The subjects in this study
      included 141 patients in the following groups: surgically confirmed CE cases
      (18), ultrasound-proven cases (26), presumptive CE cases (47), controls with
      other parasitic disease (25), and healthy controls (25). A polystyrene latex
      (0.81 microm) suspension was used as a carrier particle for hydatid antibodies in
      the test. The latex particles were sensitized with hyperimmune hydatid antiserum
      raised in rabbits. The hydatid antibody-sensitized latex particles were used for
      the detection of hydatid antigens in serum. The results of the study showed that
      the LAT could detect the circulating hydatid antigen in 13 (72%) of 18 patients
      with surgically confirmed CE, 17 (65%) of 26 patients with ultrasound-proven CE,
      and 19 (40%) of 47 presumptive cases of CE. The test detected antigen in 1 (4%)
      of 25 controls with other parasitic disease, and no antigen was detected in the
      serum of 25 healthy controls. The LAT showed a sensitivity of 72%, a specificity
      of 98%, a positive predictive value of 93%, and a negative predictive value of
      91%. The present study is the first report of the LAT for the detection of
      hydatid antigen in serum in the diagnosis of CE.

PMID- 14695091
TI  - Comparison of artificial membrane feeding with direct skin feeding to estimate
      the infectiousness of Plasmodium vivax gametocyte carriers to mosquitoes.
AB  - The efficacy of a membrane-feeding apparatus as a means of infecting Anopheles
      dirus mosquitoes with Plasmodium vivax was compared with direct feeding of
      mosquitoes on gametocyte carriers. Volunteers participating in the study were
      symptomatic patients reporting to malaria clinics in western Thailand. Direct
      mosquito feeds were conducted on 285 P. vivax-infected individuals. Four methods
      of preparing blood for the membrane-feeding apparatus were evaluated. They
      included 1) replacement of patient plasma with sera from a P. vivax-naive donor
      (n = 276), 2) replacement of patient plasma with plasma from a P. vivax-naive
      donor (n = 83), 3) replacement of patient plasma with that individual's own
      plasma (n = 80), and 4) whole blood added directly to the feeder (n = 221).
      Criteria used to compare the different methods included 1) number of feeds
      infecting mosquitoes, 2) percent of mosquitoes with oocysts, and 3) mean number
      of oocysts per positive mosquito. For most parameters, the direct- feeding method
      was not significantly different from methods that replaced patient plasma with
      sera/plasma from a P. vivax-naive donor. However, direct feeding was more
      effective than use of whole blood or blood that was reconstituted with the
      patient's own plasma. These data suggest a possible role of transmission-blocking
      antibody. The implications towards development of a membrane-feeding assay for
      the evaluation of candidate transmission-blocking malaria vaccines is discussed.

PMID- 14695092
TI  - Blocking of transmission to mosquitoes by antibody to Plasmodium vivax malaria
      vaccine candidates Pvs25 and Pvs28 despite antigenic polymorphism in field
      isolates.
AB  - We have previously demonstrated that mouse antisera against yeast-produced
      recombinant forms of the ookinete surface proteins of Plasmodium vivax (Pvs25 and
      Pvs28) blocks transmission of the homologous P. vivax (Sal I strain). In this
      study, we developed mouse and rabbit antisera against Pvs25 and Pvs28 and
      evaluated the efficacy of these vaccine candidates against natural isolates of P.
      vivax in Thailand. Although both Pvs25 and Pvs28 genes are polymorphic, sera from
      mice immunized using alum adjuvant completely inhibited oocyst development for
      most human isolates, whereas sera from rabbits immunized with either alum or
      Freund's adjuvant were partially inhibitory. All inhibition occurred in an
      antibody dose dependent fashion. Data from this study clearly demonstrates that
      antibodies raised against Sal I-based vaccines overcome the genetic polymorphism
      of Pvs25 and Pvs28 present in natural isolates of P. vivax, suggesting the wide
      range applicability of Sal I based vaccines.

PMID- 14695093
TI  - Transmission-blocking activity of tafenoquine (WR-238605) and artelinic acid
      against naturally circulating strains of Plasmodium vivax in Thailand.
AB  - The sporontocidal activity of tafenoquine (WR-238605) and artelinic acid was
      determined against naturally circulating isolates of Plasmodium vivax in western
      Thailand. Primaquine was used as a negative control and a dihydroacridine-dione
      (WR-250547) was used as a positive control. Laboratory-reared Anopheles dirus
      mosquitoes were infected with P. vivax by allowing mosquitoes to feed on blood
      (placed in an artificial-membrane feeding apparatus) collected from gametocytemic
      volunteers reporting to local malaria clinics in Tak province, Thailand. Four
      days post-infection, mosquitoes were refed on uninfected mice treated 90 minutes
      earlier with a given drug. Drug activity was determined by assessing oocyst and
      sporozoite development. Neither primaquine nor artelinic acid affected oocyst or
      sporozoite development at a dose of 100 mg of base drug/kg of mouse body weight.
      In contrast, tafenoquine and WR-250547 affected sporogonic development at doses
      as low as 25.0 and 0.39 mg/kg, respectively. The potential role of these
      compounds in the prevention of malaria transmission is discussed, as are
      alternative strategies for the use of transmission-blocking antimalarial drugs.

PMID- 14695095
TI  - Short report: in vivo sensitivity of Plasmodium falciparum to halofantrine in
      southern central Vietnam.
AB  - Drug-resistant Plasmodium falciparum is present in Vietnam. We assessed the in
      vivo sensitivity of P. falciparum to halofantrine in two villages in the southern
      part of central Vietnam. Halofantrine (8 mg/kg x 3 doses) was administered to 37
      patients with either P. falciparum (n = 32) or mixed P. falciparum/P. vivax
      malaria (n = 5). End points were parasite sensitivity or resistance (RI/RII/RIII)
      determined by parasite clearance, persistence, or recurrence during 28 days of
      follow-up. By day 28, 31 (93.9%) of 33 (95% confidence interval = 79.8-99.2%)
      patients were sensitive. Two patients had recurrent P. falciparum parasitemia on
      days 14 and 21. Halofantrine effectively treated uncomplicated P. falciparum
      malaria in these Vietnamese patients.

PMID- 14695094
TI  - Chloroquine-resistant Plasmodium vivax malaria in Peru.
AB  - Reports from several sites in South America suggest the presence of isolated
      cases of chloroquine-resistant Plasmodium vivax malaria. To investigate the
      possibility of chloroquine-resistant P. vivax in Peru, we conducted 28-day in
      vivo drug efficacy trials at three sites in the Amazon region and one site on the
      northern Pacific Coast between 1998 and 2001. A total of 242 patients between the
      ages of 2 and 60 years were enrolled (177 from the Amazon region and 65 from the
      northern coast). All subjects received directly observed therapy with
      chloroquine, 25 mg/kg, over a three-day period. On enrollment, 49% had a
      documented fever and 96% had a history of fever; their geometric mean parasite
      density was 5,129 parasites/microL. A total of 212 (88%) of the 242 subjects
      completed their 28-day follow-up. Four of the 177 patients from the Amazon region
      had a recurrence of P. vivax parasitemia on days 21 and 28 after treatment was
      initiated. Two of these patients had chloroquine-resistant infections, based on
      polymerase chain reaction-single-stranded conformational polymorphism genotyping
      and chloroquine-desethylchloroquine blood levels, which were > or = 97 ng/mL at
      the time of the reappearance of parasitemia. None of the subjects studied on the
      northern Pacific Coast had recurrent parasitemia.

PMID- 14695096
TI  - Multi-drug resistant Plasmodium falciparum malaria in Assam, India: timing of
      recurrence and anti-malarial drug concentrations in whole blood.
AB  - The susceptibility of 23 cases of Plasmodium falciparum malaria from the Sonapur
      primary health center in the Kamrup district of Assam, India to different
      antimalarials was investigated using the 28-day World Health Organization in vivo
      test. Whole blood concentrations of chloroquine, sulfadoxine, and quinine were
      determined at different intervals and at the time of parasites recrudescence
      after completion of treatment with the respective drugs to confirm the status of
      drug sensitivity. A case of multi-drug resistant P. falciparum malaria was found
      where recrudescence occurred, despite standard oral treatment with chloroquine,
      sulfadoxine/pyrimethamine, and quinine sequentially. Whole blood concentrations
      of chloroquine, sulfadoxine, and quinine at the time of recrudescence were 0.35
      microg/ml (day 7), 18 microg/ml (day 14), and 0.009 microg/ml (day 14),
      respectively. Therefore, monitoring of drug-resistant P. falciparum malaria and
      its proper treatment should be intensified to check the spread of multi-drug
      resistant strains in other parts of the country.

PMID- 14695097
TI  - Clearance of drug-resistant parasites as a model for protective immunity in
      Plasmodium falciparum malaria.
AB  - Residents of malaria-endemic areas sometimes spontaneously clear Plasmodium
      falciparum infection without drug treatment, implying an important role for host
      factors such as immunity in this clearance. Host factors may also contribute to
      clearance of parasites resistant to a treatment drug. Chloroquine resistance is
      caused by point mutations in P. falciparum chloroquine resistance transporter
      (pfcrt) gene. We investigated the clearance of malaria parasites carrying the key
      chloroquine resistance-conferring PfCRT mutation K76T in patients treated with
      chloroquine. We found that the ability to clear these resistant parasites is
      strongly dependent on age (the best surrogate for protective immunity in endemic
      areas), suggesting that host immunity plays a critical role in the clearance of
      resistant P. falciparum infections. Age-adjusted comparison of subjects able to
      clear resistant parasites and those unable to do so provides a new phenotype for
      identifying host immune and genetic factors responsible for protective immunity
      against malaria.

PMID- 14695099
TI  - Cough is an airway itch?

PMID- 14695100
TI  - Allergen-derived T cell peptides and late asthmatic responses.

PMID- 14695101
TI  - Respiratory epithelium in usual interstitial pneumonia/idiopathic pulmonary
      fibrosis: spark or destructive flame?

PMID- 14695102
TI  - Advancing therapy for pulmonary arterial hypertension: can animal models help?

PMID- 14695103
TI  - Sildenafil for pulmonary arterial hypertension: still waiting for evidence.

PMID- 14695104
TI  - Therapeutic hypercapnic acidosis: pushing the envelope.

PMID- 14695105
TI  - Protecting subjects with decisional impairment in research: the need for a
      multifaceted approach.

PMID- 14695106
TI  - Alveolar instability causes early ventilator-induced lung injury independent of
      neutrophils.
AB  - Intratracheal instillation of Tween causes a heterogeneous surfactant
      deactivation in the lung, with areas of unstable alveoli directly adjacent to
      normal stable alveoli. We employed in vivo video microscopy to directly assess
      alveolar stability in normal and surfactant-deactivated lung and tested our
      hypothesis that alveolar instability causes a mechanical injury, initiating an
      inflammatory response that results in a secondary neutrophil-mediated proteolytic
      injury. Pigs were mechanically ventilated (VT 10 cc/kg, positive end-expiratory
      pressure [PEEP] 3 cm H2O), randomized to into three groups, and followed for 4
      hours: Control group (n = 3) surgery only; Tween group (n = 4) subjected to
      intratracheal Tween (surfactant deactivator causing alveolar instability); and
      Tween + PEEP group (n = 4) subjected to Tween with increased PEEP (15 cm H2O) to
      stabilize alveoli. The magnitude of alveolar instability was quantified by
      computer image analysis. Surfactant-deactivated lungs developed significant
      histopathology only in lung areas with unstable alveoli without an increase in
      neutrophil-derived proteases. PEEP stabilized alveoli and significantly reduced
      histologic evidence of lung injury. Thus, in this model, alveolar instability can
      independently cause ventilator-induced lung injury. To our knowledge, this is the
      first study to directly confirm that unstable alveoli are subjected to ventilator
      induced lung injury whereas stable alveoli are not.

PMID- 14695108
TI  - Cost-effectiveness of computed tomography in diagnosis of pulmonary embolism.

PMID- 14695107
TI  - An indolent case of severe acute respiratory syndrome.
AB  - Severe acute respiratory syndrome (SARS) is a highly contagious and typically
      rapidly progressive form of atypical pneumonia, which spread from Asia to many
      parts of the world in early 2003. Clinical diagnosis of SARS requires the
      presence of unremitting fever and progressive pneumonia despite antibiotic
      therapy, particularly in the presence of lymphopenia and raised transaminase
      levels. We report the case of a woman who had undergone a successful allogeneic
      bone marrow transplant for acute myeloid leukemia. She presented initially with
      fever and a normal chest radiograph. Her indolent clinical course of SARS was
      punctuated by resolution of fever, but there was progressive radiologic
      deterioration and increasing serum antibody titer against SARS coronavirus.
      Treatment with oral prednisolone and ribavirin normalized her lymphopenia,
      altered transaminases, chest radiograph and high-resolution computed tomography
      appearances rapidly. Our experience should alert other clinicians in recognizing
      this atypical indolent presentation of SARS, to protect health care workers and
      the community at large and to ensure that these patients are properly treated.

PMID- 14695109
TI  - Intravenous montelukast in acute asthma.

PMID- 14695110
TI  - Eosinophils in asthma and airway hyperresponsiveness.

PMID- 14695111
TI  - Do matrix metalloproteinases protect or worsen pneumonia?

PMID- 14695112
TI  - Hypothermia and hypoxia inhibit the Hering-Breuer reflex in the marsupial
      newborn.
AB  - The effects of lowering body temperature (T(b)) on metabolic rate, ventilation,
      and the strength of the Hering-Breuer expiratory promoting reflex (HB reflex;
      determined from an inhibitory ratio calculated from volumetric measurements of
      the respiratory rhythm) were examined in 18-day-old ectothermic pouch young of
      the tammar wallaby during normoxia or hypoxia (10% O(2)). Hypoxia and
      hypothermia, either singularly or combined, depressed metabolic rate. At all
      T(b), the hypoxic hyperventilation was associated with a significant hyperpnea.
      At pouch T(b) (36.5 degrees C) during normoxia, inflation of the lungs with -5 or
      -10 cmH(2)O extrathoracic pressure induced a significant HB reflex. Exposure to
      cold reduced the strength of the reflex, almost abolishing it at 28 degrees C.
      For T(b) above 28 degrees C, the reflex in hypoxia was always less than the
      corresponding normoxic value. Taken in context with the changes in metabolic
      state that occurred, these data in the ectothermic marsupial newborn suggest that
      the decline in the HB reflex during moderate hypothermia is the result of a
      direct effect of T(b) on vagal mechanisms rather than a temperature-driven
      decline in metabolic rate that should have acted to strengthen the HB reflex.
      Therefore, it seems that inputs inhibitory to breathing are more negatively
      affected during cold than those inputs that are excitatory.

PMID- 14695113
TI  - Acute arterial hypertension inhibits proximal tubular fluid reabsorption in
      normotensive rat but not in SHR.
AB  - The effect of acute arterial hypertension on proximal tubular fluid reabsorption
      was investigated in Sprague-Dawley rats and spontaneously hypertensive rats (SHR)
      by measuring proximal tubular flow with a nonobstructive optical method. Under
      control conditions, spontaneous tubular flow was oscillating at 0.02-0.03 Hz in
      Sprague-Dawley rats. Acute hypertension induced an immediate increase of mean
      tubular flow (50% increase after 20 min of hypertension) and augmentation of
      oscillatory amplitude. Acute hypertension did not alter single-nephron blood flow
      as measured by laser-Doppler velocimetry (n = 12), suggesting that the increase
      of tubular flow was due to inhibition of reabsorption but not increase of
      filtration. By contrast, spontaneous tubular flow was fluctuating aperiodically
      in SHR. Acute hype tension did not induce a continuous increase of tubular flow
      or an increase in amplitude of fluctuations (n = 15). When apical Na(+)/H(+)
      exchange activity of proximal tubule was monitored, acute hypertension did not
      alter the activity in SHR (n = 8), while similar procedures had been shown to
      inhibit apical Na(+)/H(+) exchange activity of proximal tubules by more than 40%
      in Sprague-Dawley rats. These observations suggest that acute hypertension
      inhibits proximal tubular fluid reabsorption by inhibiting apical Na(+)/H(+)
      exchange activity in Sprague-Dawley rats and that this mechanism is impaired in
      SHR.

PMID- 14695114
TI  - Lactic and hydrochloric acids induce different patterns of inflammatory response
      in LPS-stimulated RAW 264.7 cells.
AB  - Metabolic acidosis frequently complicates sepsis and septic shock and may be
      deleterious to cellular function. Different types of metabolic acidosis (e.g.,
      hyperchloremic and lactic acidosis) have been associated with different effects
      on the immune response, but direct comparative studies are lacking. Murine
      macrophage-like RAW 264.7 cells were cultured in complete medium with lactic acid
      or HCl to adjust the pH between 6.5 and 7.4 and then stimulated with LPS
      (Escherichia coli 0111:B4; 10 ng/ml). Nitric oxide (NO), IL-6, and IL-10 levels
      were measured in the supernatants. RNA was extracted from the cell pellets, and
      RT-PCR was performed to amplify corresponding mediators. Gel shift assay was also
      performed to assess NF-kappa B DNA binding. Inc easing concentrations of acid
      caused increasing acidification of the media. Trypan blue exclusion and lactate
      dehydrogenase release demonstrated that acidification did not reduce cell
      viability. HCl significantly increased LPS-induced NO release and NF-kappa B DNA
      binding at pH 7.0 but not at pH 6.5. IL-6 and IL-10 expression (RNA and protein)
      were reduced with HCl-induced acidification, but IL-10 was reduced much more than
      IL-6 at low pH. By contrast, lactic acid significantly decreased LPS-induced NO,
      IL-6, and IL-10 expression in a dose-dependent manner. Lactic acid also inhibited
      LPS-induced NF-kappa B DNA binding. Two common forms of metabolic acidosis
      (hyperchloremic and lactic acidosis) are associated with dramatically different
      patterns of immune response in LPS-stimulated RAW 264.7 cells. HCl is essentially
      proinflammatory as assessed by NO release, IL-6-to-IL-10 ratios, and NF-kappa B
      DNA binding. By contrast, lactic acidosis is anti-inflammatory.

PMID- 14695115
TI  - Chronic exercise lowers the defended body weight gain and adiposity in diet
      induced obese rats.
AB  - The effects of running wheel exercise and caloric restriction on the regulation
      of body weight, adiposity, and hypothalamic neuropeptide expression were compared
      in diet-induced obese male rats over 6 wk. Compared with sedentary controls,
      exercising rats had reduced body weight gain (24%), visceral (4 fat pads; 36%)
      and carcass (leptin; 35%) adiposity but not insulin levels. Hypothalamic arcuate
      nucleus (ARC) proopiomelanocortin (POMC) mRNA expression was 25% lower, but ARC
      neuropeptide Y (NPY), agouti- related peptide, dorsomedial nucleus (DMN) NPY, and
      paraventricular nucleus (PVN) corticotropin- releasing hormone (CRH) expression
      was comparable to controls. Sedentary rats calorically restricted to 85% of
      control body weight reduced their visceral adiposity (24%), leptin (64%), and
      insulin (21%) levels. ARC NPY (23%) and DMN NPY (60%) were increased, while ARC
      POMC (40%) and PVN CRH (14%) were decreased. Calorically restricted exercising
      rats an half as much as ad libitum-fed exercising rats and had less visceral
      obesity than comparably restricted sedentary rats. When sedentary restricted rats
      were refed after 4 wk, they increased intake and regained the weight gain and
      adiposity of sedentary controls. While refed exercising rats and sedentary rats
      ate comparable amounts, refed exercising rats regained weight and adiposity only
      to the level of ad libitum-fed exercising rats. Thus exercise lowers the defended
      level of weight gain and adiposity without a compensatory increase in intake and
      with a very different profile of hypothalamic neuropeptide expression from
      calorically restricted rats. This may be due to exercise-related factors other
      than plasma insulin and leptin.

PMID- 14695116
TI  - Thermal injury impairs cardiac protein synthesis and is associated with
      alterations in translation initiation.
AB  - The purpose of the present study was to determine whether burn injury decreases
      myocardial protein synthesis and potential contributing mechanisms for this
      impairment. To address this aim, thermal injury was produced by a 40% total body
      surface area full-thickness scald burn in anesthetized rats, and the animals were
      studied 24 h late. Burn decreased the in vivo-determined rate of myocardial
      protein synthesis and translation efficiency by 25% but did not alter the protein
      synthetic rate in skeletal muscle. To identify potential mechanisms responsible
      for regulating mRNA translation in cardiac muscle, we examined several eukaryotic
      initiation factors (eIFs) and elongation factors (eEFs). Burn failed to alter
      eIF2B activity or the total amount or phosphorylation status of either eIF2 alpha
      or eIF2B epsilon in heart. In contrast, hearts from burned rats demonstrated 1)
      an increased binding of the translational repressor 4E-BP1 with eIF4E, 2) a
      decreased amount of eIF4E associated with eIF4G, and 3) a decreased amount of the
      hyperphosphorylated gamma-form of 4E-BP1. These changes in eIF4E availability
      were not seen in gastrocnemius muscle where burn injury did not decrease protein
      synthesis. Furthermore, constitutive phosphorylation of mTOR, S6K1, the ribosomal
      protein S6, and eIF4G were also decreased in hearts from burned rats. Burn did
      not appear to adversely affect elongation because there was no significant
      difference in the myocardial content of eEF1 alpha or eEF2 or the phosphorylation
      state of eEF2. The above-mentioned burn-induced changes in mRNA translation were
      associated with an impairment of in vitro myocardial performance. Finally, 24 h
      postburn, the cardiac mRNA content of IL-1 beta, IL-6, and high-mobility group
      protein B1 (but not TNF-alpha) was increased. In summary, these data suggest that
      thermal injury specifically decreases cardiac protein synthesis in part by
      decreasing mRNA translation efficiency resulting from an impairment in
      translation initiation associated with alterations in eIF4E availability and S6K1
      activity.

PMID- 14695117
TI  - Nitric oxide decreases endothelin-1 secretion through the activation of soluble
      guanylate cyclase.
AB  - The use of exogenous nitric oxide (NO) has been shown to alter the regulation of
      other endothelially derived mediators of vascular tone, such as endothelin-1 (ET
      1). However, the interaction between NO and ET-1 appears to be complex and
      remains incompletely understood. One of the major actions of NO is the activation
      of soluble guanylate cyclase (sGC) with the subsequent generation of cGMP.
      Therefore, we undertook this study to test the hypothesis that NO regulates ET-1
      production via the activation of the sGC/cGMP pathway. The results obtained
      indicated that the exposure of primary cultures of 4-wk-old ovine pulmonary
      arterial endothelial cells (4-wk PAECs) to the long-acting NO donor DETA NONOate
      induced both a dose- and time-dependent decrease in secreted ET-1. This decrease
      in ET-1 secretion occurred in the absence of changes in endothelin-converting
      enzyme-1 or sGC expression but in conjunction with a decrease in prepro-ET-1
      mRNA. The changes in ET-1 release were inversely proportional to the cellular
      cGMP content. Furthermore, the NO-independent activator of sGC, YC-1, or
      treatment with a cGMP analog also produced significant decreases in ET-1
      secretion. Conversely, pretreatment with the sGC inhibitor ODQ blocked the NO
      induced decrease in ET-1. Therefore, we conclude that exposure of 4-wk PAECs to
      exogenous NO decreases secreted ET-1 resulting from the activation of sGC and
      increased cGMP generation.

PMID- 14695118
TI  - Pertussis toxin activates L-arginine uptake in pulmonary endothelial cells
      through downregulation of PKC-alpha activity.
AB  - Pertussis toxin (PTX) induces activation of l-arginine transport in pulmonary
      artery endothelial cells (PAEC). The effects of PTX on l-arginine transport
      appeared after 6 h of treatment and reached maximal values after treatment for 12
      h. PTX-induced changes in l-arginine transport were not accompanied by changes in
      expression of cationic amino acid transporter (CAT)-1 protein, the main l
      arginine transporter in PAEC. Unlike holotoxin, the beta-oligomer-binding subunit
      of PTX did not affect l-arginine transport in PAEC, suggesting that Galpha(i)
      ribosylation is an important step in the activation of l-arginine transport by
      PTX. An activator of adenylate cyclase, forskolin, and an activator of protein
      kinase A (PKA), Sp-cAMPS, did not affect l-arginine transport in PAEC. In
      addition, inhibitors of PKA or adenylate cyclase did not change the activating
      effect of PTX on l-arginine uptake. Long-term treatment with PTX (18 h) induced a
      40% decrease in protein kinase C (PKC)-alpha but did not affect the activities of
      PKC-epsilon and PKC-zeta in PAEC. An activator of PKC-alpha, phorbol 12-myristate
      13-acetate, abrogated the activation of l-arginine transport in PAEC treated with
      PTX. Incubation of PTX-treated PAEC with phorbol 12-myristate 13-acetate in
      combination with an inhibitor of PKC-alpha (Go 6976) restored the activating
      effects of PTX on l-arginine uptake, suggesting PTX-induced activation of l
      arginine transport is mediated through downregulation of PKC-alpha. Measurements
      of nitric oxide (NO) production by PAEC revealed that long-term treatment with
      PTX induced twofold increases in the amount of NO in PAEC. PTX also increased l
      [(3)H]citrulline production from extracellular l-[(3)H]arginine without affecting
      endothelial NO synthase activity. These results demonstrate that PTX increased NO
      production through activation of l-arginine transport in PAEC.

PMID- 14695119
TI  - Alveolar macrophages are a primary barrier to pulmonary absorption of
      macromolecules.
AB  - We demonstrate that a primary source of elimination of inhaled macromolecules
      after delivery to the lungs and before absorption into the systemic circulation
      owes to clearance by alveolar macrophages (AM). Depletion of AM by liposome
      encapsulated dichloromethylene diphosphonate is shown to cause severalfold
      enhancement in systemic absorption of IgG and human chorionic gonadotropin after
      intratracheal instillation in rats. Lowering the doses of IgG delivered to the
      lungs alleviates local degradation and results in a dramatic increase in systemic
      absorption of the protein as well. Chemical and physical means of minimizing
      uptake of macromolecules by AM are proposed as novel methods for enhancing
      protein absorption from the lungs. Such strategies may have important
      ramifications on the development of inhalation as an attractive mode of
      administration of therapeutic proteins to the bloodstream.

PMID- 14695120
TI  - Thioredoxin liquefies and decreases the viscoelasticity of cystic fibrosis
      sputum.
AB  - The persistent and viscous nature of airway secretions in cystic fibrosis (CF)
      disease leads to airway obstruction, opportunistic infection, and deterioration
      of lung function. Thioredoxin (Trx) is a protein disulfide reductase that
      catalyzes numerous thiol-dependent cellular reductive processes. To determine
      whether Trx can alter the rheological properties of mucus, sputum obtained from
      CF patients was treated with TRX and its reducing system (0.1 microM thioredoxin
      reductase + 2 mM NADPH), and liquid phase-gel phase ratio (percent liquid phase)
      was assessed by compaction assay. Exposure to low Trx concentrations (1 microM)
      caused significant increases in the percentage of liquid phase of sputum. Maximal
      increases in percent liquid phase occurred with 30 microM Trx. Additional
      measurements revealed that sputum liquefaction by the Trx reducing system is
      dependent on NADPH concentration. The relative potency of the Trx reducing system
      also was compared with other disulfide-reducing agents. In contrast with Trx,
      glutathione and N-acetylcysteine were ineffective in liquefying sputum when used
      at concentrations <1 mM. Sputum viscoelasticity, measured by magnetic
      microrheometry, also was diminished significantly following 20-min treatment with
      3, 10, or 30 microM Trx. Similarly, this reduction in viscoelasticty also was
      dependent on NADPH concentration. Further investigation has indicated that Trx
      treatment increases the solubility of high-molecular-weight glycoproteins and
      causes redistribution of extracellular DNA into the liquid phase of sputum.
      Recognizing that mucins are the major gel-forming glycoproteins in mucus, we
      suggest that Trx alters sputum rheology by enzymatic reduction of glycoprotein
      polymers present in sputum.

PMID- 14695126
TI  - Kin I kinesins: insights into the mechanism of depolymerization.
AB  - Kin I kinesins are members of the diverse kinesin superfamily of molecular
      motors. Whereas most kinesins use ATP to move along microtubules, Kin I kinesins
      depolymerize microtubules rather than walk along them. Functionally, this
      distinct subfamily of kinesins is important in regulating cellular microtubule
      dynamics and plays a crucial role in spindle assembly and chromosome segregation.
      The molecular mechanism of Kin I-induced microtubule destabilization is as yet
      unclear. It is generally believed that Kin Is induce a structural change on the
      microtubule that leads to microtubule destabilization. Recently, much progress
      has been made towards understanding how Kin Is may cause this structural change,
      and how ATPase activity is employed in the catalytic cycle.

PMID- 14695127
TI  - Metabolism of inorganic N compounds by ammonia-oxidizing bacteria.
AB  - Ammonia oxidizing bacteria extract energy for growth from the oxidation of
      ammonia to nitrite. Ammonia monooxygenase, which initiates ammonia oxidation,
      remains enigmatic given the lack of purified preparations. Genetic and
      biochemical studies support a model for the enzyme consisting of three subunits
      and metal centers of copper and iron. Knowledge of hydroxylamine oxidoreductase,
      which oxidizes hydroxylamine formed by ammonia monooxygenase to nitrite, is
      informed by a crystal structure and detailed spectroscopic and catalytic studies.
      Other inorganic nitrogen compounds, including NO, N2O, NO2, and N2 can be
      consumed and/or produced by ammonia-oxidizing bacteria. NO and N2O can be
      produced as byproducts of hydroxylamine oxidation or through nitrite reduction.
      NO2 can serve as an alternative oxidant in place of O2 in some ammonia-oxidizing
      strains. Our knowledge of the diversity of inorganic N metabolism by ammonia
      oxidizing bacteria continues to grow. Nonetheless, many questions remain
      regarding the enzymes and genes involved in these processes and the role of these
      pathways in ammonia oxidizers.

PMID- 14695128
TI  - Of peptides and peptidases: the role of cell surface peptidases in cancer.

PMID- 14695129
TI  - Cancer immunotherapy targeting survivin: commentary re: V. Pisarev et al., full
      length dominant-negative survivin for cancer immunotherapy. Clin. Cancer Res.,
      9:6523-6533, 2003.

PMID- 14695130
TI  - The proteasome as a target for cancer therapy.
AB  - The proteasome is a multicatalytic proteinase complex responsible for the
      degradation of most intracellular proteins, including proteins crucial to cell
      cycle regulation and programmed cell death, or apoptosis. In preclinical cancer
      models, proteasome inhibitors induce apoptosis, have in vivo antitumor efficacy,
      and sensitize malignant cells and tumors to the proapoptotic effects of
      conventional chemotherapeutics and radiation therapy. Interestingly, transformed
      cells display greater susceptibility to proteasome inhibition than nonmalignant
      cells. Therefore, proteasome inhibition holds promise as a novel approach to the
      treatment of cancer. Inhibitors of the proteasome impact on cells in part through
      down-regulation of nuclear factor kappaB, but also through modulation of cell
      cycle proteins and other pro- and antiapoptotic pathways. Bortezomib (VELCADE;
      formerly PS-341), the first such inhibitor to undergo clinical testing, has
      demonstrated impressive antitumor activity and manageable toxicities in Phase I
      and II trials both as a single agent, and in combination with other drugs. It has
      been approved recently by the Food and Drug Administration for therapy of
      patients with multiple myeloma who have received at least two prior regimens and
      progressed on the last of these. Ongoing preclinical evaluations of the
      mechanisms that underlie the antitumor effects of proteasome inhibitors, and
      clinical trials in a variety of tumor types, will allow additional refinement of
      the role these agents will play in cancer therapy. Below we discuss the rationale
      behind targeting the proteasome for cancer therapy, and review the preclinical
      and clinical data on proteasome inhibitors alone, and in combination with
      conventional chemotherapeutics.

PMID- 14695131
TI  - Detection and clinical implications of early systemic tumor cell dissemination in
      breast cancer.
AB  - Blood-borne distant metastasis is the leading cause of cancer-related death in
      breast cancer. The onset of this fundamental process can now be assessed in
      cancer patients using ultrasensitive immunocytochemical and molecular assays able
      to detect even single metastatic cells. Analyses of bone marrow (BM) samples show
      that disseminated cells are present in 20-40% of primary breast cancer patients
      without any clinical or histopathological signs of metastasis. The common homing
      of circulating breast cancer cells in BM is indicative for systemic tumor cell
      spread and predictive for growth of overt metastases in relevant organ sites such
      as bone, lung, or liver. Recent clinical studies involving more than 3000 breast
      cancer patients demonstrated that the presence of tumor cells in BM at primary
      diagnosis is an independent prognostic factor for unfavorable clinical outcome.
      To date, sampling of BM, however, is not a routine procedure in clinical
      management of breast cancer patients. Therefore, several research groups have
      developed sensitive assays for detection of circulating tumor cells in peripheral
      blood. Studies evaluating the clinical relevance of these blood assays are
      ongoing. Here, we will review the existing tumor cell assays and discuss their
      current clinical relevance and perspectives for the clinical management of breast
      cancer patients.

PMID- 14695132
TI  - Pharmacokinetics and pharmacodynamics of plasma clofarabine and cellular
      clofarabine triphosphate in patients with acute leukemias.
AB  - PURPOSE: The purpose of our study was to investigate the pharmacology of
      clofarabine and its triphosphate and the pharmacodynamic actions in circulating
      blasts obtained from acute leukemia patients who entered a Phase I clinical trial
      of clofarabine. EXPERIMENTAL DESIGN: Adults with refractory acute leukemias
      including lymphoblastic (ALL), myelogenous (AML) and chronic myelogenous leukemia
      in blastic phase (CML-BP) received clofarabine from 4 mg/m(2) to 55 mg/m2/day for
      5 days as a 1-h i.v. infusion. A total of 26 of the 32 patients were studied for
      pharmacological investigations. RESULTS: The maximum tolerated dose was 40
      mg/m2/day for 5 days. Plasma pharmacology studies done in 25 patients indicate a
      linear increase in the plasma clofarabine concentration with increasing doses. At
      40 mg/m2 the median plasma clofarabine level was 1.5 micro M (range, 0.42-3.2
      micro M; n = 7). Cellular pharmacokinetic studies done at the end of the first
      clofarabine infusion in 26 patients appeared dose proportional but showed a wide
      variation in the concentrations of clofarabine triphosphate. At the maximum
      tolerated dose, the concentration was a median 19 micro M (range, 3-52 micro M).
      In the majority of cases, more than 50% of the analog triphosphate was present at
      24 h after infusion. Compared with clofarabine triphosphate concentration, the
      endogenous level of dATP was low, resulting in a favorable ratio of analog
      triphosphate:normal deoxynucleoside triphosphate (dNTP) for incorporation into
      DNA. In association with the accumulation of triphosphate, there was a decrease
      in DNA synthesis. At 40- and 55-mg/m2 doses, the inhibition of DNA synthesis was
      maintained to 24 h. CONCLUSIONS: Clofarabine at the maximum tolerated dose was
      effective with regard to inhibition of DNA synthesis and decline in circulating
      leukemia blasts. Given the clinical activity of clofarabine in adult acute
      leukemias, it is of interest to conduct a detailed characterization of the
      cellular pharmacology of clofarabine triphosphate and its relationship to
      clinical responses.

PMID- 14695133
TI  - Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular
      melanoma metastatic to liver.
AB  - PURPOSE: Liver metastases are the sole or life-limiting component of disease in
      the majority of patients with ocular melanoma who recur. Because median survival
      after diagnosis of liver metastases is short and no satisfactory treatment
      options exist, we have conducted clinical trials evaluating isolated hepatic
      perfusion (IHP) for patients afflicted with this condition. EXPERIMENTAL DESIGN:
      Twenty-nine patients (male: 14, female: 15; mean age, 49 years) with unresectable
      liver metastases from ocular melanoma were treated with a 60-min hyperthermic IHP
      using 1.5 mg/kg of melphalan (mean total dose 105 mg). Via laparotomy, perfusion
      inflow was established with a cannula in the gastroduodenal artery and outflow
      via a cannula positioned in an isolated segment of the retrohepatic inferior vena
      cava. Portal and infra-renal inferior vena cava blood flow was shunted externally
      to the axillary vein using a veno-veno bypass circuit. Patients were assessed for
      toxicity, radiographic response, and survival. RESULTS: There was no treatment
      related mortality and transient grade 3/4 hepatic toxicity was observed in 19
      patients (65%). Mean length of operation and hospital stay was 8.3 h and 10 days,
      respectively. There were 3 (10%) complete responses (duration: 12, 14+, 15
      months) and 15 partial responses (52%; mean duration: 10 months). The initial
      site of disease progression included liver in 17 of 25 patients (68%) who
      recurred. At a median follow-up of 30.7 months the median actuarial progression
      free and overall survivals were 8 and 12.1 months, respectively. CONCLUSIONS: IHP
      with melphalan alone results in significant regression of established liver
      metastases for patients with ocular melanoma. However, after IHP, disease
      progression is most commonly observed in the liver, and survival after disease
      progression is short. On the basis of a pattern of tumor progression
      predominantly in liver, continued clinical evaluation of hepatic directed therapy
      in this patient population is justified.

PMID- 14695134
TI  - Assessment of inter- and intrapatient variability in C15O2 positron emission
      tomography measurements of blood flow in patients with intra-abdominal cancers.
AB  - PURPOSE: The aim of the study was to evaluate the inter- and intrapatient
      variability of positron emission tomography (PET) measurements of perfusion in
      advanced solid cancers. EXPERIMENTAL DESIGN: Thirty-seven patients with
      predominantly intra-abdominal tumors underwent PET imaging using inhaled C15O2.
      Repeat data were obtained by scanning five patients twice, 1 week apart, with no
      intervening therapy. Regional flow and the volume of distribution (V(d)) were
      measured from dynamic images by use of a one-compartment model. Inter- and
      intrapatient variability were measured as the coefficient of variability (CV).
      Data were also obtained for regions of interest in normal liver, spleen, and
      kidney. RESULTS: The mean (+/-SD) regional flow in the tumors was 0.46 +/- 0.19
      ml(blood)/min/ml(tissue), and the mean V(d) was 0.74 +/- 0.15
      ml(blood)/ml(tissue). Variability in tumor flow was greater between (n = 37; CV =
      41%) than within (n = 5; CV = 11%) patients. Variability in tumor V(d) was
      greater between (CV = 21%) than within (CV = 6%) patients. There was a good
      correlation between the repeat tumor data for both regional flow (rho = 0.82; P =
      0.023) and V(d) (rho = 0.89; P = 0.007). Normal tissue variability was also
      greater between than within patients. In all cases, no statistically significant
      differences were seen between repeat measurements in the same patient.
      CONCLUSIONS: Dynamic C15O2 PET measurements of regional flow are reproducible in
      patients with predominantly intra-abdominal malignancies and may be useful for
      the pharmacodynamic evaluation of novel antivascular and antiangiogenic cancer
      therapeutic agents.

PMID- 14695135
TI  - Correlation of primary tumor prostate-specific membrane antigen expression with
      disease recurrence in prostate cancer.
AB  - PURPOSE: The restricted expression of the surface glycoprotein prostrate-specific
      membrane antigen (PSMA) to normal prostate tissue, primary and metastatic
      prostate cancer (PCa), and the neovasculature of various nonprostatic epithelial
      malignancies has enabled targeting strategies for PCa treatment using anti-PSMA
      antibodies. EXPERIMENTAL DESIGN: Using prostatectomy specimens,
      immunohistochemical staining for PSMA (7E11 antibody) was performed on formalin
      fixed paraffin-embedded sections of 136 cases of PCa. Cytoplasmic
      immunoreactivity was scored for intensity and distribution, and results were
      correlated with tumor grade, pathological stage, DNA ploidy status (Feulgen
      spectroscopy), and disease recurrence. PSMA mRNA expression in selected primary
      tumors and metastatic lesions was also detected using in situ hybridization and
      autoradiography. RESULTS: Generally, PCa cells expressed relatively increased
      levels of PSMA as compared with benign elements. Among the PCa cases, increased
      (high) PSMA expression correlated with tumor grade (P = 0.030), pathological
      stage (P = 0.029), aneuploidy (P = 0.010), and biochemical recurrence (P =
      0.001). The mean serum prostate-specific antigen level of 18.28 ng/ml at the time
      of diagnosis for the PSMA-overexpressing tumors was significantly greater than
      the mean serum prostate-specific antigen of 9.10 ng/ml for the non-PMSA
      overexpressing group (P = 0.006). On multivariate analysis, pathological stage (P
      = 0.018) and PSMA expression (P = 0.002) were independent predictors of
      biochemical recurrence. PSMA protein overexpression in high-grade primary PCa
      tumors and metastatic lesions also correlated with increased PSMA mRNA expression
      levels using in situ hybridization and autoradiography. CONCLUSIONS: This study
      demonstrates for the first time that overexpression of PSMA in primary PCa
      correlates with other adverse traditional prognostic factors and independently
      predicts disease outcome.

PMID- 14695136
TI  - Vascular endothelial growth factor independently predicts the efficacy of
      postoperative radiotherapy in node-negative breast cancer patients.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is a mediator of angiogenesis
      and is up-regulated under hypoxic conditions. Hypoxic tumors are known to exhibit
      resistance to radiotherapy. We investigated the association between VEGF levels
      in tumor tissue and the effect of radiotherapy for relapse-free survival (RFS)
      and overall survival (OS) in node-negative breast cancer. EXPERIMENTAL DESIGN:
      The study was performed on 489 patients; 221 patients received postoperative
      radiotherapy as part of the breast-conserving therapy (BCT), and 268 patients
      were treated by mastectomy only. VEGF levels were measured using a quantitative
      ELISA. None of the patients received adjuvant systemic therapy. The median follow
      up was 64 months (range, 2-149) after BCT and 59 months (range, 2-117) after
      mastectomy. Correlations with well-known prognostic factors were studied, and
      univariate and multivariate survival analyses were performed. RESULTS: Only in
      the BCT group, high VEGF levels (equal or above the median level) predicted a
      reduced RFS and OS in univariate survival analysis (P = 0.004 and P = 0.028,
      respectively), implying that patients with high VEGF levels have less benefit
      from BCT. This was seen as a significant interaction between local treatment and
      VEGF for the total population for RFS (P = 0.012) and OS (P = 0.004). The
      interaction between local treatment and tumor size was also significant for both
      RFS (P = 0.046) and OS (P = 0.019) in the multivariate analysis. CONCLUSIONS:
      These results show that, in node-negative patients, both tumor size and VEGF
      content predict for a reduced efficacy of postoperative radiotherapy as part of
      BCT, indicating that the choice of local treatment of these patients can also be
      modified based on tumor VEGF content.

PMID- 14695137
TI  - Transcription factor Sp1 expression is a significant predictor of survival in
      human gastric cancer.
AB  - The transcription factor Sp1 regulates the expression of multiple genes. However,
      its expression and role in human tumor development and progression remain
      unclear. Using immunohistochemistry, we investigated Sp1 expression patterns in
      86 cases of human gastric cancer having various clinicopathologic
      characteristics, 57 normal gastric tissue specimens, and 53 lymph node
      metastases. We found that Sp1 protein was expressed predominantly in the nuclei
      of cells located in the mucous neck region, whereas Sp1 expression was not
      detected either in the cells located toward the gastric pit (foveolar
      differentiation) or cells of the glandular epithelium (glandular
      differentiation). In sharp contrast, strong Sp1 expression was detected in tumor
      cells, whereas no or very weak Sp1 expression was detected in stromal cells and
      normal glandular cells surrounding or within the tumors. We also evaluated the
      effect of Sp1 expression on the survival of patients who have undergone surgical
      resection. The median survival duration in patients who had a tumor with
      negative, weak, and strong Sp1 expression was 43, 37, and 8 months, respectively
      (P = 0.0075). Next, Sp1 expression, stage, completeness of resection, age, and
      sex were entered into a Cox proportional hazard model. In multivariate analysis,
      Sp1 (P = 0.003) and stage (P < 0.001) were independently prognostic of survival.
      Therefore, normal and malignant gastric tissues have unique Sp1 expression
      patterns. Given the importance of Sp1 in the expression of multiple molecules key
      to tumor cell survival, growth, and angiogenesis, its disregulated expression and
      activation may play important roles in gastric cancer development and
      progression.

PMID- 14695138
TI  - Interleukin-13 receptor alpha2 chain in human head and neck cancer serves as a
      unique diagnostic marker.
AB  - Previous studies have demonstrated that approximately 30% of squamous cell
      carcinoma of the head and neck (SCCHN) cell lines express high levels of
      interleukin-13 receptor(s) (IL-13R). However, the incidence, expression level,
      and significance of IL-13R expression in human tumor specimens is not known. In
      addition, it is not known whether normal head and neck tissues express IL-13R. In
      this study, we evaluated the expression of IL-13R subunits (IL-13Ralpha1, IL
      13Ralpha2, and IL-4Ralpha) in 337 surgically excised specimens of SCCHN and
      normal head and neck tissues. Specimens were obtained from 139 patients with
      SCCHN and 16 patients with benign tonsil disorders from two centers in the United
      States and Japan and evaluated with immunohistochemistry and in situ
      hybridization. Extensive analysis demonstrated that the majority of SCCHN tumors
      uniformly expressed low levels of IL-13Ralpha1 chain; however, 77% of the tumors
      expressed moderate to high levels of IL-4Ralpha, which forms a signaling complex
      with IL-13Ralpha1 chain. On the other hand, 33% of SCCHN tumors expressed
      moderate to high levels of IL-13Ralpha2 chain. Using tissue array from 99
      patients, we observed that the expression levels of IL-13Ralpha2 and IL-4Ralpha
      were significantly higher in SCCHN than in normal head and neck tissues (P <
      0.005). Detailed analysis of clinicopathological features demonstrated a positive
      statistically significant correlation between IL-13Ralpha2 expression and
      clinically advanced primary SCCHN tumor (T(4); Tumor-Node-Metastasis
      classification; P < 0.05). However, there was no correlation among IL-13R
      expression and sex, age of patients, stage of lymph node metastasis, squamous
      cell carcinoma grade, or allergic history. Taken together, this study suggests
      that IL-13R may be involved in SCCHN tumor progression, and 33% of IL-13Ralpha2
      positive SCCHN cases may be targeted by IL-13 cytotoxin and IL-13R-targeted
      agent.

PMID- 14695139
TI  - Aberrant promoter methylation and silencing of laminin-5-encoding genes in breast
      carcinoma.
AB  - PURPOSE: Down-regulation of Laminin-5 (LN5)-encoding genes (LAMA3, LAMB3, and
      LAMC2) has been reported in various human cancers. However, the mechanism of
      inactivation was not clearly understood until recently. In this study, we
      investigated the loss of expression of three LN5-encoding genes in breast cancer
      cell lines and elucidated the mechanism of silencing of the genes in breast
      cancer cell lines and tumors. EXPERIMENTAL DESIGN: We examined the expression of
      the three LN5-encoding genes by reverse transcription-PCR in breast cancer cell
      lines (n = 20). To elucidate the mechanism of silencing, we treated expression
      negative cell lines (n = 5) with a demethylating agent and examined restoration
      of expression by reverse transcription-PCR. By using methylation-specific primers
      designed by us, we validated the methylation status of the promoter regions in
      breast cancer cell lines using methylation-specific PCR. We additionally studied
      the methylation patterns in primary breast tumors (n = 74) and correlated the
      data with clinical parameters. RESULTS: We observed varied losses of expression
      (10-55%) of LN5-encoding genes in breast cancer cell lines. Expression of one or
      more genes was lost in 65% of breast cancer cell lines. Treatment of expression
      negative cell lines with demethylating agent restored expression in all cases.
      Methylation frequencies of LAMA3, LAMB3, and LAMC2 genes in 20 breast cancer cell
      lines were 40, 5, and 15%, respectively. The concordances between loss of
      expression and methylation in 20 breast cancer cell lines for the three genes (85
      95%) were statistically significant. Nonmalignant breast tissues (n = 30) had
      very low frequencies of methylation (0-7%). In 74 breast tumors, methylation
      frequencies LAMA3, LAMB3, and LAMC2 were 44, 4, and 20%, respectively. The
      differences in methylation frequencies between cell lines and tumors were not
      statistically significant for all of the three genes. The methylation frequencies
      of LAMA3 and mean chain methylation index in cell lines and tumors were
      significantly different from methylation frequencies in nonmalignant tissues, and
      they were significantly higher in high stage and large size tumors as compared
      with low-stage and small size tumors. LAMA3 promoter methylation frequency in
      breast tumors was associated with increased tumor stage (P < 0.001) and tumor
      size (P < 0.001). CONCLUSIONS: Our results demonstrate epigenetic inactivation of
      LN5-encoding genes in breast cancers and association of LAMA3 promoter
      methylation with increased tumor stage and tumor size. Our findings are of
      biological interest and potentially of clinical importance.

PMID- 14695140
TI  - Aberrant promoter methylation of laminin-5-encoding genes in prostate cancers and
      its relationship to clinicopathological features.
AB  - PURPOSE: Laminin-5 (LN5) is an essential component of the basement membrane (BM)
      and is composed of three chains that are the products of three distinct genes
      (LAMA3, LAMB3, and LAMC2). Differential expression of LN5 genes has been reported
      in prostate and other cancers. Recently, in lung cancers, we developed
      methylation-specific PCR assays for each gene and demonstrated that the aberrant
      methylation as the mechanism of inactivation of genes. In this study, we
      investigated the aberrant promoter methylation of LN5 genes in prostate cancers
      and correlated the data with clinicopathological features. EXPERIMENTAL DESIGN:
      Promoter methylation of LN5-encoding genes was analyzed in 101 prostate cancer
      samples by methylation-specific PCR assay. In addition, we analyzed 32
      nonmalignant prostate tissue samples. The methylation index (MI) was determined
      as the methylated fraction of the genes examined. RESULTS: The frequencies of
      loss of expression for the LAMA3, LAMB3, and LAMC2 genes in six prostate cancer
      cell lines were 83, 67, and 50%, respectively, whereas the methylation
      frequencies were 83, 67, and 33%, respectively. The concordances between loss of
      expression and methylation for the three genes were 100, 100, and 83%,
      respectively. The frequency of methylation of LN5-encoding genes in prostate
      cancers and nonmalignant prostate tissues, respectively, were: 44 and 12% for
      LAMA3 (P = 0.001); 18 and 6% for LAMB3; and 41 and 9% for LAMC2 (P = 0.001). In
      addition, methylation frequencies of any one or two genes, frequencies of at
      least one-gene methylation and mean chain MI were significantly higher in
      prostate cancers than in nonmalignant prostate tissues. For clinicopathological
      correlations, the high Gleason score (GS) group, high preoperative serum prostate
      specific antigen (PSA) group, and high stage group had significantly higher
      methylation frequencies of LAMA3 than their corresponding low groups. Methylation
      frequency of at least one gene and mean chain MI was significantly higher in the
      high PSA group and high-stage group than their respective low groups. There was
      significant correlation between MI and PSA. The high GS group had higher
      frequencies of at least one gene methylation and mean chain MI than the low GS
      group. CONCLUSIONS: Our results demonstrate frequent epigenetic silencing of LN5
      encoding genes in prostate cancers and it correlates with clinicopathological
      features of poor prognosis. These findings are of biological interest and
      potentially of clinical importance.

PMID- 14695141
TI  - Loss of caspase-8 protein expression correlates with unfavorable survival outcome
      in childhood medulloblastoma.
AB  - PURPOSE: Escaping apoptosis is a hallmark of cancer. In medulloblastoma (MB) cell
      lines, resistance to tumor necrosis factor-related apoptosis-inducing ligand
      induced apoptosis was recently shown to correlate with loss of caspase-8 mRNA
      expression, because of aberrant gene methylation (M. A. Grotzer et al., Oncogene,
      19: 4604-4610, 2000). Loss of caspase-8 mRNA expression has been demonstrated in
      a subset of primary MB (T. J. Zuzak et al., Eur. J. Cancer, 38: 83-91, 2002). In
      this study, we analyzed primary MB samples to test whether loss of caspases
      correlates with survival outcome. EXPERIMENTAL DESIGN: We used
      immunohistochemistry to analyze the protein expression of the key initiator
      caspase-8 and caspase-9 in paraffin-embedded tumor samples from 77 well
      characterized MB patients and compared the expression levels of caspase-8 and
      caspase-9 with apoptosis indices, clinical variables, and survival outcomes.
      RESULTS: Weak expression of caspase-8 and caspase-9 was found in 16 and 24% of
      the MB samples evaluated, respectively. Weak expression of caspase-8 was an
      independent significant prognostic factor for unfavorable progression-free
      survival outcome and was more predictive than standard clinical factors. In
      contrast, caspase-9 expression was not a prognostic factor. Treatment of caspase
      8-deficient MB cells with IFN-gamma resulted in dose-dependent restoration of
      caspase-8 mRNA and protein expression and restoration of tumor necrosis factor
      related apoptosis-inducing ligand sensitivity. CONCLUSIONS: Loss of initiator
      caspase-8 is associated with an unfavorable survival outcome. Restoration of
      caspase-8 (e.g., by treatment with IFN-gamma) might, therefore, represent a novel
      experimental therapy in childhood MB.

PMID- 14695142
TI  - Identification of HRK as a target of epigenetic inactivation in colorectal and
      gastric cancer.
AB  - PURPOSE: Aberrant methylation of CpG islands can be a good molecular marker for
      identifying genes inactivated in cancer. We found the proapoptotic gene HRK to be
      a target for hypermethylation in human cancers and examined the role of such
      methylation in silencing the gene's expression. EXPERIMENTAL DESIGN: Methylation
      of HRK was evaluated by bisulfite-PCR and bisulfite sequencing in a group of
      colorectal and gastric cancer cell lines and primary cancers. Gene expression and
      histone acetylation were examined by reverse transcription-PCR and chromatin
      immunoprecipitation analyses, respectively. Apoptosis of cancer cells after
      treatment with a DNA methyltransferase inhibitor and/or histone deacetylase
      inhibitor was examined with fluorescence-activated cell-sorting analysis.
      RESULTS: The region around the HRK transcription start site was methylated in 36%
      of colorectal and 32% of gastric cancer cell lines and was closely associated
      with loss of expression in those cell types. HRK expression was restored by
      treatment with a methyltransferase inhibitor, 5-aza-deoxycytidine, and enhanced
      further by addition of histone deacetylase inhibitor trichostatin A or
      depsipeptide. Such restoration of HRK expression was well correlated with
      induction of apoptosis and enhancement of Adriamycin-induced apoptosis.
      Expression of other proapoptotic genes, including BAX, BAD, BID, and PUMA, was
      unaffected by treatment with 5-aza-deoxycytidine. Aberrant methylation of HRK was
      also frequently detected in primary colorectal cancers that showed methylation of
      multiple genes, including p16INK4A and hMLH1, and was associated with wild-type
      p53. CONCLUSION: HRK methylation can be a useful molecular target for cancer
      therapy in a subset of colorectal and gastric cancers.

PMID- 14695143
TI  - Detection of mutations in the mitogen-activated protein kinase pathway in human
      melanoma.
AB  - PURPOSE: Recent studies suggest that activating point mutations in B-RAF may
      commonly occur in melanoma. We devised a method to detect point mutations in
      heterogeneous tissues containing both wild-type and mutant B-RAF and N-RAS genes
      by using site-directed mutagenesis to introduce new restrictions sites in the
      cDNA sequence when the specific point mutations are present. We used this
      technique to determine the incidence of mitogen-activated protein kinase (MAPK)
      mutations in human melanoma. EXPERIMENTAL DESIGN: We screened 85 melanoma samples
      for the most common B-RAF and N-RAS mutations found in melanoma using a site
      directed mutagenesis-based detection technique. Western blotting was used to
      evaluate downstream up-regulation of the mitogen-activated protein kinase pathway
      in these tissues. RESULTS: Thirty-three samples (7 of 25 primaries, 15 of 25
      regional metastases, 5 of 25 nodal metastases, and 6 of 10 distant metastases)
      harbored the V599E B-RAF mutation (39%), 12 contained a Q61R N-RAS mutation and 5
      a Q61K N-RAS mutation. Western blotting with antiphosphorylated extracellular
      signal-regulated kinase 1/2 antibodies demonstrated up-regulation of the MAPK
      pathway in samples containing activating B-RAF or N-RAS mutations compared with
      wild-type samples. This method of detection was sensitive and specific with no
      false positives. CONCLUSIONS: Activating mutations of the MAPK pathway were
      present in approximately 60% of samples tested and caused activation of this
      cellular pathway that appears to be important in the pathogenesis of melanoma.

PMID- 14695144
TI  - Progression of cervical carcinomas is associated with down-regulation of CD9 but
      strong local re-expression at sites of transendothelial invasion.
AB  - PURPOSE AND EXPERIMENTAL DESIGN: Lymphovascular space invasion plays a critical
      role in the progression of cervical cancer and is an indicator of an unfavorable
      prognosis, even in patients with early-stage disease. Identification and
      functional characterization of molecules that are predominantly expressed in
      tumors able to penetrate lymphatic vessels may therefore help to improve the
      clinical assessment of cervical neoplasias with unclear prognosis. We used
      immunohistochemical staining to assess expression of the tetraspanin adapter
      protein CD9 in cervical tumors because inverse correlations with tumor
      invasiveness, ability to form metastases, and poor clinical outcome have been
      described for several other tumor types. RESULTS AND CONCLUSION: We found that
      CD9, strongly expressed by cells forming the basal layer of normal squamous
      epithelium of the cervix, is down-regulated in most invasive cervical carcinomas
      (correlation with stage, P = 0.015) but apparently re-expressed at distinct
      regions during tumor progression. Tumor sites with pronounced localized
      expression of CD9 (CD9 hotspots) include cones growing into blood or lymphatic
      vessels, pointing to a functional role of CD9 in transendothelial migration as a
      crucial step in the formation of lymph node metastases. Remarkably, CD9 hotspots
      were found to be a highly significant (P < 10(-5)) indicator of lymphangiosis:
      they were observed in 15 of 18 cases with histopathologically confirmed
      lymphangiosis compared with 4 of 26 other cervical carcinomas. We postulate,
      therefore, that clusters of tumor cells characterized by strong expression of CD9
      may be useful as an indicator of high risk of recurrence in early-stage cervical
      cancer, providing a basis for clinical decisions in favor of additional
      treatment.

PMID- 14695145
TI  - Prognostic value of rho GTPases and rho guanine nucleotide dissociation
      inhibitors in human breast cancers.
AB  - PURPOSE: Rho family members are small GTPases that are known to regulate
      malignant transformation and motility of cancer cells. The activities of Rhos are
      regulated by molecules such as guanine nucleotide dissociation inhibitors (GDIs).
      This study determined the levels of expression and the distribution of Rho-A, -B,
      -C, and -G, and Rho-6, -7, and -8, as well as Rho-GDI-beta, and Rho-GDI-gamma, in
      breast cancer and assessed their prognostic value. EXPERIMENTAL DESIGN: The
      distribution and location of Rhos and RhoGDIs were assessed using
      immunohistochemical staining of frozen sections. The levels of transcripts of
      these molecules were determined using a real-time quantitative PCR. Levels of
      expression were analyzed against nodal involvement and distant metastasis, grade,
      and survival over a 6-year follow-up period. RESULTS: The levels of Rho-C, Rho-6,
      and Rho-G were significantly higher in breast cancer tissues (n = 120) than in
      background normal tissues (n = 32). However, the level of Rho-A and -B and rho-7
      and -8 was found to be similar in tumor and normal tissues. Immunohistochemical
      staining revealed the high level of staining of Rho-C protein in tumor cells. The
      levels of Rho-GDI-gamma transcripts were found to be significantly lower in tumor
      tissues than in normal tissues (P < 0.05 and P < 0.001, respectively). Node
      positive tumors have significantly higher levels of Rho-C and Rho-G, and lower
      levels of Rho-GDI and Rho-GDI-gamma transcripts, than do node-negative tumors.
      Significantly higher levels of Rho-C and Rho-G were seen in patients who died of
      breast cancer than in those who remained disease free. Patients with recurrent
      disease, with metastasis or who died of breast cancer, also exhibited higher
      levels of Rho-6 but lower levels of Rho-GDI-gamma. Higher-grade tumors were also
      associated with low levels of Rho-GDI and Rho-GDI-gamma. CONCLUSIONS: Raised
      levels of Rho-C, Rho-G and Rho-6 and reduced expression of Rho-GDI and -GDI-gamma
      in breast tumor tissues are correlated with the nodal involvement and metastasis.
      This suggests that the expression of Rhos and Rho-GDIs in breast cancer is
      unbalanced and that this disturbance has clinical significance in breast cancer.

PMID- 14695146
TI  - Rapid and sensitive detection of messenger RNA expression for molecular
      differential diagnosis of renal cell carcinoma.
AB  - PURPOSE: The aim of this study was to develop a practical technique to detect
      mRNA expression and to validate a panel of mRNA markers for molecular
      differential diagnosis of renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: The
      renal cancer cell line SKRC-52 was used to set up the technique, which consisted
      of column extraction of RNA and one-step reverse transcription-PCR. We validated
      a panel of gene markers, including MN/CA9, cadherin-6, vimentin, mucin1, and
      parvalbumin, and studied 50 renal tumors (30 conventional, 9 papillary, and 5
      chromophobe RCCs and 6 oncocytomas), 10 normal tissues, and 10 normal blood
      samples. We mimicked fine needle aspiration (FNA) biopsy in 10 kidneys with
      conventional RCC and applied this technique to 10 preoperative FNA samples from
      imaging-indeterminate renal tumors. RESULTS: The technique could detect as few as
      10 SKRC-52 cells with MN/CA9 as mRNA marker and was less time consuming and labor
      intensive. MN/CA9 was a sensitive and rather specific gene marker for
      conventional RCC. Cadherin-6 gene expression was a sensitive marker for
      conventional and papillary RCC. Vimentin was highly specific for conventional
      RCC. Mucin1 mRNA was sensitive for papillary and chromophobe RCC and oncocytoma.
      Parvalbumin mRNA was a sensitive and highly specific marker for both chromophobe
      RCC and oncocytoma. Thus, these mRNA markers represent the biomarker genes for
      the subtypes of renal tumors. Finally, we successfully applied the technique to
      FNA specimens. Five preoperative FNA samples were MN/CA9 gene positive,
      suggesting a RCC, whereas the routine cytology was positive in only three cases.
      CONCLUSIONS: A rapid and sensitive assay of mRNA markers was developed for
      molecular differential diagnosis of RCC. This molecular assay can be used as a
      powerful ancillary to surgical pathological diagnosis and cytological diagnosis
      of RCC.

PMID- 14695147
TI  - The role of an 80 kDa fragment of E-cadherin in the metastatic progression of
      prostate cancer.
AB  - PURPOSE: The purpose of this study was to evaluate an 80 kDa proteolytic fragment
      of E-cadherin as a potential biomarker for prostate cancer progression and to
      identify putative proteases that are responsible for the cleavage of E-cadherin.
      EXPERIMENTAL DESIGN: A wide spectrum of prostate cancer tissue and serum
      specimens representing different stages of prostate cancer was examined for the
      accumulation of the 80 kDa fragment of E-cadherin. Additionally, an expression
      array analysis was used to identify putative proteases that may have been
      involved in the cleavage of E-cadherin. RESULTS: A reproducible E-cadherin
      fragment was detected as a strong 80 kDa band in tissue samples. This fragment
      was detectable almost exclusively in metastatic sites. It was not visible in
      normal prostate tissue and was weak in 1 of 16 localized prostate cancers. The
      fragment is shed into the extracellular space and was detectable in patient serum
      in which the expression of the fragment showed a strong association with advanced
      prostate cancer. On the basis of cDNA expression analysis, several members of the
      metalloproteinase family could be identified as potentially responsible for the
      cleavage of the fragment from full-length E-cadherin. CONCLUSIONS: In this study,
      we present the first report of serum levels of the 80 kDa fragment of E-cadherin
      in prostate cancer patients. This fragment is exclusively seen in neoplastic
      prostate tissue and may represent a useful biomarker of prostate cancer disease
      progression. This study also demonstrates an association of increased levels of
      several metalloproteinases with metastatic prostate cancer and could provide a
      useful correlation between metalloproteinase expression/activity and E-cadherin
      cleavage and the metastatic progression of prostate cancer.

PMID- 14695148
TI  - Expression of the MAGE-A4 and NY-ESO-1 cancer-testis antigens in serous ovarian
      neoplasms.
AB  - PURPOSE: The cancer-testis (CT) family of antigens is expressed in a variety of
      malignant neoplasms and is silent in normal tissues, except for the testis.
      Expression of two members of this family, MAGE-A4 and NY-ESO-1, has been
      described in melanomas, germ cell tumors, certain carcinomas and sarcomas, and
      more recently in uterine neoplasms. The objective of this study was to evaluate
      the extent and prognostic significance of CT antigen expression in ovarian serous
      neoplasms. EXPERIMENTAL DESIGN: Seventy-four patients with ovarian neoplasms,
      including 10 with serous cystadenomas, 11 with serous tumors of borderline
      malignancy, and 53 with serous carcinomas, were studied. Immunohistochemistry was
      performed with the 57B monoclonal antibody, which recognizes predominantly the
      MAGE-A4 antigen and the D8.38 antibody that recognizes NY-ESO-1. RESULTS: MAGE-A4
      expression was found to be present in 57% of the serous carcinomas and only in 9%
      of the serous tumors of borderline malignancy. No staining was detected in serous
      cystadenomas or in the normal ovary. In 8 of 30 positively stained serous
      carcinomas, >50% of the tumor cells expressed MAGE-A4. NY-ESO-1 expression was
      seen in 19% of the serous carcinomas, whereas serous tumors of borderline
      malignancy and cystadenomas were negative. A significant inverse correlation was
      found between MAGE-A4 expression and patient survival (P = 0.016). Multivariate
      analysis revealed that both tumor stage and MAGE-A4 expression were independent
      predictors of patient survival (P = 0.022 and P = 0.013, respectively).
      CONCLUSIONS: Cancer-testis antigen expression in ovarian serous neoplasms
      correlates directly with their degree of malignancy. MAGE-A4 expression, and to a
      lesser degree NY-ESO-1 expression, is characteristic of the majority of serous
      carcinomas. Determining the degree of MAGE-A4 expression in these tumors may
      provide important prognostic information. Finally, MAGE-A4 may represent a novel
      target for immunotherapy in serous ovarian neoplasms.

PMID- 14695149
TI  - Epidermal growth factor receptor, p53 mutation, and pathological response predict
      survival in patients with locally advanced esophageal cancer treated with
      preoperative chemoradiotherapy.
AB  - PURPOSE: Despite the availability of cellular markers associated with cell cycle,
      apoptosis, and DNA repair, predictive factors for pathological complete response
      (CR) and overall survival (OS) are few in patients with locally advanced
      esophageal cancer. This study evaluates the role of clinical and cellular markers
      in predicting CR and OS in patients with esophageal cancer. EXPERIMENTAL DESIGN:
      Patients were treated with infusional cisplatin and 5-fluorouracil combined with
      daily radiotherapy followed by esophagectomy. Pretreatment tumors (n = 54) were
      analyzed for epidermal growth factor receptor (EGF-R), bax, and bcl-2 expression
      by immunohistochemistry and for p53 mutations by direct DNA sequencing of exons 5
      8. Clinical covariates included patients' age at enrollment; gender; Barrett's
      metaplasia; and tumor location, histology, and differentiation. Logistic
      regression and survival analyses were used to evaluate the predictors. RESULTS:
      Age ranged from 32 to 75 years; most patients were male (45 male; 9 female); and
      tumors were distal (47 distal; 7 mid), adenocarcinoma (41 adenocarcinomas; 13
      squamous cell carcinomas), and moderately differentiated (33 moderate; 6 well; 15
      poor). Female gender predicted CR (odds ratio 7.5; 95% confidence interval, 1.4
      41). The OS was 43% at 5 years. Presence of CR (P < 0.001 log rank) and p53
      mutation (P = 0.051 log rank) correlated with increased OS, whereas increased EGF
      R expression predicted poor OS (P = 0.009 log rank). EGF-R remained significant
      when adjusted for clinical covariates. There was a trend toward increased OS
      related to better tumor differentiation and decreased bcl-2. CONCLUSIONS: These
      data suggest that EGF-R and p53 mutation may be used as both outcome predictors
      and targets for molecular therapy for esophageal cancer.

PMID- 14695150
TI  - Detection of human papillomavirus in cervical lymph nodes: a highly effective
      strategy for localizing site of tumor origin.
AB  - PURPOSE: Patients with head and neck squamous cell carcinoma (HNSCC) often come
      to clinical attention with a neck mass due to metastatic spread to lymph nodes.
      Treatment is dictated by the subsequent determination of primary tumor site and
      stage. However, the primary site remains elusive in some patients even after an
      exhaustive examination. Human papillomavirus type 16 (HPV-16) is an important
      etiologic agent for HNSCCs that arise within the oropharynx but less so for
      tumors from nonoropharyngeal sites. Detection of HPV-16 or a surrogate marker may
      be useful in localizing tumor origin in patients who present with metastatic
      HNSCC. EXPERIMENTAL DESIGN: We performed in situ hybridization (ISH) for HPV-16
      on lymph node metastases from 68 patients with HNSCC. P16 immunohistochemistry
      was also performed because HPV-16 integration disrupts the retinoblastoma pathway
      and induces an overexpression of p16. RESULTS: HPV-16 was detected in 22 of the
      68 (32%) cases by ISH. When stratified by site of origin, HPV-16 was detected in
      22 of 31 (71%) metastases from the oropharynx, but in none of the 37 (0%)
      metastases from other sites (P < 0.001; Fisher's exact). P16 expression was
      associated with the presence of HPV-16 by ISH: 21 of 22 HPV-16 positive tumors
      exhibited p16 expression, whereas only 4 of the 46 HPV-16-negative tumors were
      p16 positive (95% versus 9%; P < 0.001; Fisher's exact). P16 expression in the
      node metastases also correlated with site of tumor origin: 24 of 31 oropharyngeal
      tumors were p16 positive, whereas only 1 of 37 nonoropharyngeal tumors was p16
      positive (77% versus 3%; P < 0.001; Fisher's exact). CONCLUSIONS: For patients
      with metastatic HNSCC, detection of HPV-16 is a reliable way to establish origin
      from the oropharynx, either directly by ISH or indirectly by immunohistochemistry
      for p16 overexpression.

PMID- 14695151
TI  - Frequent loss of heterozygosity targeting the inactive X chromosome in melanoma.
AB  - After previous preliminary observations of paradoxical deletion events affecting
      the inactive X chromosome in melanoma, we have surveyed the X chromosome for
      deletions using 23 polymorphic microsatellite markers in 28 informative (female
      XX) metastatic melanomas. Ten tumors (36%) showed at least one loss of
      heterozygosity (LOH) event, and in two cases an entire chromosome showed LOH at
      all informative loci. Four distinct X chromosome smallest regions of overlap can
      be resolved. An 18.6-Mb region on the p arm involving 9 of 28 (32%) samples lies
      between the markers DXS1061 and DXS1068. An equally frequently deleted smallest
      region of overlap straddled the centromere, bounded by DX1204 on the p arm and
      DXS983 14.6 Mb away in Xq11-12. One tumor potentially defines this region more
      tightly to a 10.6-Mb smallest region of overlap bounded by DXS1190 and DXS981
      that contains the androgen receptor (AR) gene. A 6.2-Mb deleted region can be
      defined between the markers DXS8051 and DXS9902 in 8 of 28 (28%) tumors. An
      additional, less frequently deleted region of 25.7 Mb was found on distal Xq
      between the markers DXS1212 and DXS1193 in 5 of 28 (18%) tumors. X inactivation
      analysis of five tumors with LOH, using the AR exon 1 CAG repeat, showed that in
      each case, the inactive, hypermethylated allele was the one deleted. Analysis of
      copy number in this region by quantitative PCR showed restoration to disomy and,
      in one case, trisomy at AR.

PMID- 14695152
TI  - NRAS and BRAF mutations arise early during melanoma pathogenesis and are
      preserved throughout tumor progression.
AB  - PURPOSE: Recently, it was reported that BRAF mutations are frequent in melanoma.
      Previously, we analyzed a large series of paired primary and metastatic melanomas
      for NRAS codon 61 mutations and showed that they arise early and are preserved
      during tumor progression. Here, we have screened the same tumor samples for BRAF
      mutations. EXPERIMENTAL DESIGN: Primary melanomas (n = 71) and corresponding
      metastases (n = 88) from 71 patients were screened for BRAF exon 11 and exon 15
      mutations using single-strand conformational polymorphism and nucleotide sequence
      analysis RESULTS: BRAF mutations were found in 42 of 71 patients (59%). Thirty
      seven patients had mutations that lead to a Val599Glu change, whereas mutations
      resulting in Gly468Ser, Val599Arg, Val599Lys, and Lys600Glu changes were detected
      in one patient each. Furthermore, one patient had a 6-bp insertion between codons
      598 and 599, encoding two threonine residues. In most cases, paired primary and
      metastatic lesions had the same BRAF genotype (i.e., mutations present in the
      primary tumors were preserved in the corresponding metastases, and mutations did
      not arise at the metastatic stage if they were not present in the primary
      lesion). Using laser-capture microdissection, BRAF mutations were found in the
      radial growth phase of the primary lesions. BRAF mutations occurred exclusively
      in tumors that were wild type for NRAS, and in total, 89% of the patients
      analyzed (63 of 71) had mutations in either of these two genes. CONCLUSIONS: The
      Ras-Raf-mitogen-activated protein kinase/extracellular signal-regulated kinase
      extracellular signal-regulated kinase signaling pathway is activated in the vast
      majority of melanomas. Activation occurs through either NRAS or BRAF mutations,
      both of which arise early during melanoma pathogenesis and are preserved
      throughout tumor progression.

PMID- 14695153
TI  - Prognostic value of apoptosis-regulating protein expression in anal squamous cell
      carcinoma.
AB  - PURPOSE: This study evaluated the prognostic value of pro and antiapoptotic
      protein expression, as well as that of spontaneous apoptosis, in anal carcinoma
      patients treated by radiotherapy (RT) with or without chemotherapy. EXPERIMENTAL
      DESIGN: Ninety-eight patients with available pretreatment biopsy specimens were
      studied. Patients had been treated with split-course RT: 30-40 Gy fractionated
      external beam, followed by a 20-22-Gy boost using interstitial or external RT.
      Fifty-one patients also received concomitant mitomycin-C and 5-fluorouracil.
      Median follow-up for surviving patients was 124 months. Tissue sections were
      examined immunohistochemically for expression of proapoptotic proteins (Bax,
      p53), antiapoptotic proteins (Bcl-2, Mcl-1), and spontaneous apoptosis (M30).
      Except for M30, staining of less than 5% of tumor cells was considered negative.
      Protein expression was correlated with local tumor control (LC) and disease-free
      survival (DFS) outcomes. The Kaplan-Meier method was used for the monovariate
      analysis and the Cox proportional hazard models for the multivariate analysis.
      RESULTS: For LC, beside advanced T- and N-categories and longer overall treatment
      time (OTT), lack of Bcl-2 expression was associated with poorer 5-year outcome
      (62 versus 84%, P = 0.009). For DFS, advanced T- and N-categories, longer OTT,
      and the lack of Bcl-2 expression correlated significantly with lower rates. In
      the multivariate analysis, N-category (P = 0.0026), OTT (P = 0.04), Bcl-2 (P =
      0.0015), and M30 (P = 0.035) expressions were significant factors for LC. For
      DFS, age (P = 0.049) an N-category (P < 0.0001), as well as expression of Bcl-2
      (P = 0.001), p53 (P = 0.003), and M30 (P = 0.03), were found to be independent
      significant variables. Patients with Bcl-2(+)/p53(-) tumors had a significantly
      higher 5-year LC compared with patients whose tumors were Bcl-2(-)/p53(+) (93
      versus 53%, P = 0.004). CONCLUSIONS: Bcl-2 and particularly the combination of
      p53 and Bcl-2 expression may prove to be useful predictors of tumor response to
      RT or radiochemotherapy in anal carcinomas. Patients having tumors that are Bcl
      2(-) and p53(+) may require intensified radiochemotherapy or adoption of an
      alternative therapeutic approach.

PMID- 14695154
TI  - Adipocyte-derived leucine aminopeptidase suppresses angiogenesis in human
      endometrial carcinoma via renin-angiotensin system.
AB  - PURPOSE: Angiotensin (Ang) II was reported to induce vascular endothelial growth
      factor (VEGF) expression in various cells. Adipocyte-derived leucine
      aminopeptidase (A-LAP) is a novel member of the M1 family of zinc
      metallopeptidases. Enzymatic characterization demonstrated that A-LAP hydrolyzes
      Ang II. This study examined the role of A-LAP in angiogenesis of human
      endometrial carcinoma. EXPERIMENTAL DESIGN: We investigated whether Ang II
      induces VEGF expression in human endometrial carcinoma cells. To investigate the
      possible function of A-LAP in angiogenesis of endometrial carcinoma, we
      transfected A-LAP cDNA into HEC-1A cells, showing the lowest expression of A-LAP.
      RESULTS: In the present study, we showed that Ang II enhanced VEGF expression in
      a dose-dependent manner in endometrial carcinoma cells (HEC-1A cells).
      Overexpression of A-LAP attenuated Ang II-induced VEGF expression in HEC-1A
      cells. In addition, Human umbilical vascular endothelial cell migration was
      increased in conditioned media from Ang II-treated wild-type cells, but not in
      conditioned media from Ang II-treated A-LAP-overexpressing cells (HEC-1A-A-LAP
      cells). In an in vivo study, we showed that A-LAP overexpression in endometrial
      carcinoma cells results in a reduction of VEGF immunoreactivity and the number of
      blood vessels within tumors. CONCLUSIONS: Our study demonstrates that it is
      feasible to overexpress Ang II-degrading enzymes in cultured cells and that this
      overexpression attenuated some effects of exogenous and endogenous Ang II. These
      experiments are a first step toward the development of novel strategies to
      selectively antagonize locally generated Ang II and suppress VEGF-induced
      angiogenesis in endometrial carcinoma.

PMID- 14695155
TI  - Interferon-gamma-induced sensitization of colon carcinomas to ZD9331 targets
      caspases, downstream of Fas, independent of mitochondrial signaling and the
      inhibitor of apoptosis survivin.
AB  - We have demonstrated previously a Fas-dependent component in thymineless death of
      human colon carcinoma cells. Importantly, the cytotoxic effects of thymidine
      deprivation induced by 5-fluorouracil (FUra) combined with leucovorin (LV) was
      enhanced by IFN-gamma, and the synergism was shown to be dependent on Fas, FUra
      induced DNA damage, and independent of p53. Subsequently we examined the
      potential for synergistic interactions between IFN-gamma and the specific
      thymidylate synthase inhibitor, ZD9331. IFN-gamma sensitized colon carcinomas to
      ZD9331-induced apoptosis and loss in clonogenic survival, also dependent on
      ZD9331-induced DNA damage, independent of p53. Synergism occurred in HCT116,
      demonstrating previously RNA-mediated FUra/LV cytotoxicity that could not be
      potentiated by IFN-gamma. Manipulation of the Fas death receptor pathway from the
      level of the receptor (Nok1/Nok2, Fas overexpression, and DN-FADD) to the
      mitochondria (Bcl-xL and Bcl-2) did not modulate ZD9331 +/- IFN-gamma-induced
      cytotoxicity in HT29, with the exception that Nok1/Nok2-blocking antibodies
      partially protected HT29 from the cytotoxic activity of ZD9331 alone. However,
      IFN-gamma alone (but not ZD9331) up-regulated the expression of caspases -3, -4, 
      7, and -8, and in combination with ZD9331 demonstrated enhanced caspase
      activation and cleavage of poly(ADP-ribose) polymerase that was not prevented by
      overexpression of Bcl-2. Additionally, IFN-gamma increased the activity of the
      proteasome in HT29, leading to selective down-regulation of the antiapoptotic
      protein survivin, whereas simultaneously increasing Fas expression. However,
      reduction in the survivin:Fas ratio by transfection of survivin small interfering
      RNA and/or overexpression of Fas did not affect sensitivity of HT29 to ZD9331 +/-
      IFN-gamma. Data demonstrate that IFN-gamma combined with ZD9331 is synergistic in
      additional cell lines that demonstrate RNA-mediated FUra/LV cytotoxicity, and
      that a major target of interaction is at the level of caspases, downstream of
      Fas, and independent of involvement of either the mitochondria or survivin.

PMID- 14695156
TI  - Antitumor therapy with bacterial DNA and toxin: complete regression of
      established tumor induced by liposomal CpG oligodeoxynucleotides plus interleukin
      13 cytotoxin.
AB  - Despite urgent need, no single strategy has been widely effective at controlling
      the growth of rapidly progressive solid tumors. We demonstrate here a potent
      antitumor therapy using modified bacterial DNA and toxin. Treatment of human head
      and neck cancer established as xenografts in athymic mice with immunostimulatory
      CpG oligodeoxynucleotides encapsulated in sterically stabilized cationic liposome
      [(CpG ODN)(SSCL)] and recombinant interleukin-13 Pseudomonas exotoxin (IL13-PE)
      significantly reduced the tumor growth followed by complete regression in most
      animals. The antitumor activity of (CpG ODN)(SSCL) was dependent on natural
      killer cells that infiltrated within tumors. Interestingly, IL13-PE enhanced (CpG
      ODN)(SSCL)-induced natural killer cell activity and cytokine production in vivo
      and in vitro. These data strongly suggest that a combination of innate immune
      activation by (CpG ODN)(SSCL) and tumor-directed targeting by IL13-PE is a novel
      approach for human cancer immunotherapy.

PMID- 14695157
TI  - Full-length dominant-negative survivin for cancer immunotherapy.
AB  - PURPOSE: The goal of this study is to investigate the possible utility of
      dendritic cells (DCs) transduced with the human full-length dominant-negative
      survivin for cancer immunotherapy. EXPERIMENTAL DESIGN: Mononuclear cells were
      collected from HLA-A2-positive healthy volunteers and patients with prostate
      cancer. DCs were transduced with an adenoviral vector containing a full-length,
      dominant-negative survivin gene. After three rounds of stimulation, the T-cell
      response against three different survivin-derived HLA-A2-matching peptides was
      tested in IFN-gamma enzyme-linked immunospot and CTL assays. RESULTS: Seven of
      eight healthy volunteers and cancer patients showed a significant response to at
      least two different survivin-derived epitopes in the enzyme-linked immunospot
      assay. One patient responded to only one peptide. All four healthy volunteers and
      two of three patients tested demonstrated a specific CTL response against T2
      target cells loaded with one survivin-derived epitope. Two donors and two
      patients had a significant CTL response against two different epitopes.
      Significant cytotoxic activity was seen against HLA-A2-positive MCF-7 tumor cells
      that express survivin. That response was specific for survivin and was MHC class
      I restricted. Because survivin is expressed in CD34(+) hematopoietic progenitor
      cells (HPCs), we tested whether the antisurvivin CTLs can recognize normal HPCs.
      The incubation of survivin-specific CTLs with CD34(+) cells did not significantly
      decrease the colony-forming ability of HPCs. CONCLUSIONS: DCs transduced with
      dominant-negative survivin induce potent survivin-specific CTL responses able to
      recognize and kill tumor cells. This response does not significantly affect HPCs.
      Thus, this study may provide rationale for immunotherapeutic clinical trials
      using a DC vaccine transduced with the dominant-negative survivin.

PMID- 14695158
TI  - Inhibition of platelet-derived growth factor receptor phosphorylation by STI571
      (Gleevec) reduces growth and metastasis of human pancreatic carcinoma in an
      orthotopic nude mouse model.
AB  - PURPOSE: We evaluated the expression of platelet-derived growth factor (PDGF)
      ligands and receptors in clinical specimens of human pancreatic adenocarcinomas
      and determined the therapeutic effect of STI571 (Gleevec), a protein tyrosine
      kinase inhibitor of PDGF receptor (PDGFR), on human pancreatic carcinoma cells
      growing in the pancreas and liver of nude mice. EXPERIMENTAL DESIGN:
      Immunohistochemical staining for PDGF-AA and -BB ligands, PDGFR-alpha and -beta,
      and phosphorylated PDGFR-alpha and -beta was performed on 31 specimens of human
      pancreatic cancer and L3.6pl human pancreatic adenocarcinoma cell line. To
      determine the in vivo effects of STI571, nude mice with L3.6pl cells injected
      into the pancreas were randomized 7 days later to receive one of the following
      treatments: sterile water p.o. (control), STI571, gemcitabine, or a combination
      of STI571 and gemcitabine. RESULTS: In 29 of 31 clinical specimens of human
      pancreatic adenocarcinoma, both tumor cells and tumor-associated endothelial
      cells expressed phosphorylated PDGFR-alpha and -beta. L3.6pl cells growing in
      culture expressed moderate amounts of PDGF-AA and little to no PDGFR-alpha or 
      beta, whereas L3.6pl cells growing in the pancreas of nude mice expressed a high
      level of PDGF and receptors. Colocalization immunohistochemical analysis
      demonstrated expression of activated PDGFR-beta by tumor-associated endothelial
      cells in both the pancreas and in liver metastases. Tumors of mice treated for 4
      weeks with STI571 (50 mg/kg or 100 mg/kg p.o. daily) were slightly smaller than
      controls. Tumors treated with gemcitabine and STI571 (50 mg/kg) were >70% smaller
      than tumors in control mice and 36% smaller than those in mice treated with
      gemcitabine only (P < 0.0002 and P < 0.04, respectively). Combination therapy
      also inhibited spontaneous metastasis to the liver. Tumors from mice treated with
      both STI571 and gemcitabine had decreased expression of activated
      (phosphorylated) PDGFR-alpha and -beta, decreased mean vessel density, decreased
      cell proliferation, and increased apoptosis of tumor cells. CONCLUSIONS:
      Collectively, these data show that activated PDGFR on tumor cells and tumor
      endothelial cells can be a novel target for therapy of pancreatic carcinoma.

PMID- 14695159
TI  - Improvement of the antitumor activity of intraperitoneally and orally
      administered 5,6-dimethylxanthenone-4-acetic acid by optimal scheduling.
AB  - PURPOSE: 5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a new anticancer drug that
      has recently completed Phase I clinical trial, is effective against
      transplantable murine tumors with established vasculature. We wished to determine
      the relationship between administration schedule and antitumor activity.
      EXPERIMENTAL DESIGN: C57Bl/6 mice with s.c. implanted Colon 38 tumors were used
      for determination of maximal tolerated doses and tumor growth delay. Plasma and
      tissue DMXAA concentrations were measured by high-performance liquid
      chromatography. RESULTS: Continuous infusion (30 mg/kg/day for 3 days) and daily
      i.p. administration schedules (7.5 mg/kg) were ineffective. A pharmacokinetically
      guided schedule was developed to increase tumor tissue drug concentrations
      without increasing the maximal plasma concentration. A schedule comprising a
      loading dose (25 mg/kg, i.p.) followed by supplementary doses (5 mg/kg after 4
      and 8 h) provided a 1.6-fold increase in tumor tissue area under the
      concentration-time curve, no increased toxicity, and superior antitumor activity
      (100% cure rate, as compared with 55% for a single i.p. dose of 25 mg/kg). A
      similar strategy was developed for oral administration with a loading dose (30
      mg/kg) and supplementary doses (15 mg/kg after 4 and 8 h). It provided a 90% cure
      rate, in contrast to a single oral dose (0% cure rate). CONCLUSIONS: The
      antitumor action of DMXAA is schedule dependent, and the achievement of an
      adequate tumor tissue DMXAA concentration above a threshold value appears to be
      critical for activity. The use of a pharmacokinetically guided schedule provides
      excellent oral activity against Colon 38 tumors and provides a basis for
      developing more effective administration schedules in clinical trials.

PMID- 14695160
TI  - In vivo fate of folate-targeted polyethylene-glycol liposomes in tumor-bearing
      mice.
AB  - PURPOSE: To compare the in vivo tissue distribution of folate-targeted liposomes
      (FTLs) injected i.v. in mice bearing folate receptor (FR)-overexpressing tumors
      (mouse M109 and human KB carcinomas, and mouse J6456 lymphoma) to that of
      nontargeted liposomes (NTLs) of similar composition. EXPERIMENTAL DESIGN: A small
      fraction of a folate-polyethylene-glycol (PEG)-distearoyl
      phosphatidylethanolamine conjugate was incorporated in FTLs. Both FTLs and NTLs
      were PEGylated with a PEG-distearoyl-phosphatidylethanolamine conjugate to
      prolong circulation time. Liposomes were labeled with [(3)H]cholesterol hexadecyl
      ether with or without doxorubicin loading. Liposome levels in plasma, tissues, or
      ascites were assessed by the number of [(3)H] counts. For doxorubicin-loaded
      formulations, we also determined the tissue doxorubicin levels by fluorimetry. To
      estimate the amount of liposomes directly associated with tumor cells in vivo, we
      determined the [(3)H]radiolabel counts in washed pellets of ascitic tumor cells
      using the ascitic J6456 lymphoma RESULTS: FTLs retained the folate ligand in
      vivo, as demonstrated by their ability to bind ex vivo to FR-expressing cells
      after prolonged circulation and extravasation into malignant ascitic fluid. In
      comparison with NTLs, FTLs were cleared faster from circulation as a result of
      greater liver uptake. Despite the lower plasma levels, tumor levels of FTL
      injected mice were not significantly different from those of NTL-injected mice.
      When NTLs and FTLs were loaded with doxorubicin, liver uptake decreased because
      of liver blockade, and uptake by spleen and tumor increased. When tumor-to-tissue
      liposome uptake ratios were analyzed, the targeting profile of FTLs was
      characterized by higher tumor:skin, and tumor:kidney ratios but lower tumor:liver
      ratio than NTLs. After a concomitant dose of free folic acid, FTLs (but not NTLs)
      plasma clearance and liver uptake were inhibited, indicating that accelerated
      clearance was mediated by the folate ligand. Surprisingly tumor uptake was not
      significantly affected by a codose of folic acid. In the J6456 ascitic tumor
      model, tumor cell-associated liposome levels were significantly greater for FTL
      injected mice than for NTL-injected mice, despite slightly higher levels of the
      latter in whole ascites. CONCLUSIONS: Whereas folate targeting does not enhance
      overall liposome deposition in tumors, the targeting profile of tumor versus
      other tissues is substantially different and intratumor liposome distribution in
      ascitic tumors is affected favorably with a selective shift toward liposome
      association with FR-expressing cells.

PMID- 14695161
TI  - A fully human antimelanoma cellular adhesion molecule/MUC18 antibody inhibits
      spontaneous pulmonary metastasis of osteosarcoma cells in vivo.
AB  - PURPOSE: The melanoma cellular adhesion molecule, also known as MUC18, is highly
      expressed on several tumors, including bone sarcomas. The level of MUC18
      expression has been found to correlate directly with tumor progression and
      metastatic potential. These observations have established MUC18 as a candidate
      mediator of tumor growth and metastasis, and suggest that blockade of MUC18 might
      be a potential target for immunotherapy against several MUC18-expressing tumors,
      including human bone sarcomas. EXPERIMENTAL DESIGN: To investigate whether
      blockade of MUC18 might be a potential target for immunotherapy against
      osteosarcoma, we have recently developed a fully human anti-MUC18 antibody, ABX
      MA1. We studied the effect of ABX-MA1 on growth, adhesion, invasion, and
      metastasis of human osteosaroma cells both in vitro and in vivo. RESULTS: MUC18
      was widely expressed on both osteosarcoma and Ewing's sarcoma cells. ABX-MA1 had
      no effect on the proliferation of osteosarcoma cells in vitro, nor did it
      significantly inhibit the growth of KRIB human osteosarcoma cells when they were
      orthotopically implanted into the tibias of nude mice. However, after 6 weeks,
      significantly fewer ABX-MA1-treated mice developed spontaneous pulmonary
      metastases than did IgG-treated control mice. Additionally, ABX-MA1 decreased the
      invasion of osteosarcoma cells through Matrigel-coated filters and disrupted
      homotypic adhesion between osteosarcoma cells and their heterotypic interaction
      with human vascular endothelial cells. CONCLUSIONS: Our findings demonstrate that
      MUC18 plays a central role in the metastasis of osteosarcoma and suggest that
      targeted inhibition of this antigen by ABX-MA1 may be a novel immunotherapeutic
      approach in the management of this tumor.

PMID- 14695162
TI  - Cure of SCID mice bearing human B-lymphoma xenografts by an anti-CD74 antibody
      anthracycline drug conjugate.
AB  - PURPOSE: The purpose of this research was to test the therapeutic efficacy of an
      anthracycline-antibody conjugate for the treatment of human B-cell lymphoma in a
      preclinical animal model. EXPERIMENTAL DESIGN: Doxorubicin (dox) conjugates of
      the murine and humanized versions of the anti B-cell antibody LL1, targeting
      CD74, were prepared, along with a nonspecific control dox-antibody conjugate,
      targeting carcinoembryonic antigen. Antibody conjugates carried approximately 8
      10 drug molecules attached site-specifically at thiols of reduced interchain
      disulfide bonds. Conjugates were tested, initially in vitro, and then for
      therapeutic efficacy in a systemic model, using a lethal i.v. dose of Raji cells
      in SCID mice. RESULTS: Dox-LL1 conjugates were shown to be stable and 3-fold more
      effective in vitro against the human B-cell Burkitt's lymphoma line, Raji,
      compared with the nonspecific control conjugate that did not target CD74 or B
      cells. When SCID mice were given an i.v. dose of 2.5 million Raji cells, they
      would die of disseminated disease within 15-25 days postinjection. A single dose
      of dox-LL1 conjugate, 117-350 micro g, given 5 days to 14 (advanced disease) days
      after injection of the Raji cells resulted in cure of most animals out to 180
      days after injection of the cells, whereas animals in treatment control groups
      were not cured. The dose of dox-LL1 found useful in this work corresponds with a
      significantly lower drug dose than reported previously with other drug-antibody
      conjugates CONCLUSION: CD74 appears to be a uniquely useful target antigen for
      delivery of drugs, effecting cures of animals with single, low doses of
      conjugate.

PMID- 14695163
TI  - Harnessing apoptosis for improved anticancer gene therapy.
AB  - Advances in our understanding of the mechanisms by which tumor cells detect drug
      induced DNA damage leading to apoptotic death have aided in the design of novel,
      potentially more selective strategies for cancer treatment. Several of these
      strategies use proapoptotic factors and have shown promise in sensitizing tumor
      cells to the cytotoxic actions of traditional cancer chemotherapeutic drugs.
      Although antiapoptotic factors are generally regarded as poor prognostic factors
      for successful cancer chemotherapy, strategies that use antiapoptotic factors in
      combination with suicide or other gene therapies can also be considered. The
      introduction of antiapoptotic factors that act downstream of drug-induced
      mitochondrial transition delays, but does not block, the ultimate cytotoxic
      response to cancer chemotherapeutic drugs that activate a mitochondrial pathway
      of cell death. Recent studies using the cytochrome P-450 prodrug cyclophosphamide
      exemplify how the antiapoptotic, caspase-inhibitory baculovirus protein p35 can
      be combined with P-450 gene-directed enzyme prodrug therapy to prolong localized,
      intratumoral production of cytotoxic drug metabolites without inducing tumor cell
      drug resistance. This model may be adapted to other gene therapies, including
      those that target death receptor pathways, to maximize the production of soluble,
      bystander cytotoxic factors and prodrug metabolites and thereby amplify the
      therapeutic response.

PMID- 14695164
TI  - Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain
      heterozygosity.
AB  - Whereas biallelic neurofibromatosis 1 (NF1) inactivation is observed in NF1
      associated gliomas, astrocyte-restricted Nf1 conditional knockout mice do not
      develop gliomas. These observations suggest that NF1 glioma formation requires
      additional cellular or genetic conditions. To determine the effect of an Nf1
      heterozygous brain environment on NF1 glioma formation, we generated Nf1+/- mice
      lacking Nf1 expression in astrocytes. In contrast to astrocyte-restricted Nf1
      conditional knockout mice, Nf1+/- mice lacking Nf1 in astrocytes develop optic
      nerve gliomas. This mouse model demonstrates that Nf1+/- cells contribute to the
      pathogenesis of gliomas in NF1 and provides a tool for the preclinical evaluation
      of potential therapeutic interventions for these tumors.

PMID- 14695165
TI  - Hyper-recombination and genetic instability in BLM-deficient epithelial cells.
AB  - Genetic instability appears to be required for a normal colorectal epithelial
      cell to evolve into a cancerous one. Bloom syndrome patients have a strong
      predisposition to cancer that affects a variety of tissues. The mechanism of
      disease is attributed to genomic instability, but many questions about the nature
      of this instability have not yet been answered. To investigate these issues, we
      used gene-targeting techniques to disrupt the BLM gene in karyotypically stable
      colorectal cancer epithelial cells. BLM knockout cells showed an increased
      tendency of sister chromatids to exchange DNA strands and were substantially more
      likely to undergo homologous recombination at chromosomal loci than parental
      cells. Surprisingly, BLM-deficient colorectal cancer epithelial cells did not
      display gross chromosomal rearrangements nor a change in the rates of chromosome
      gains and losses. However, the enhanced homologous recombination was associated
      with losses of heterozygosity. These observations define a type of genetic
      instability that has significant implications for the evolution of cancer.

PMID- 14695166
TI  - Use of complete coverage array comparative genomic hybridization to define copy
      number alterations on chromosome 3p in oral squamous cell carcinomas.
AB  - Loss of 3p has been associated with oral cancer progression and is common in many
      cancers. However, regions of alteration on 3p are poorly defined. We have
      constructed a high-resolution chromosomal array using a tiling set of 535 human
      bacterial artificial chromosomes that provides near complete coverage of 3p.
      Array comparative genomic hybridization analysis of 20 microdissected oral
      squamous cell carcinomas showed multiple and recurrent segments of copy number
      changes. These include a deletion containing the FHIT gene; novel segments of
      copy decrease at 3p22, 3p24, and 3p26; and an unexpected approximately 0.7 Mbp
      segmental increase at 3p21. These data strongly support the value of using
      chromosomal array comparative genomic hybridization for detailed profiling of
      oral squamous cell carcinomas.

PMID- 14695167
TI  - 53BP1 and NFBD1/MDC1-Nbs1 function in parallel interacting pathways activating
      ataxia-telangiectasia mutated (ATM) in response to DNA damage.
AB  - 53BP1 and NFBD1/MDC1 are recruited rapidly to sites of DNA double-strand breaks
      (DSBs), where they are hypothesized to function downstream of the ataxia
      telangiectasia mutated (ATM) checkpoint kinase as "mediators" of DNA DSB
      signaling. To test this hypothesis, we suppressed 53BP1 and NFBD1/MDC1 expression
      by small interference RNA and monitored ATM autophosphorylation at Ser(1981) as a
      marker for ATM activation. Suppression of NFBD1/MDC1 led to decreased ATM
      activation and phosphorylation of ATM substrates. This phenotype was identical to
      that observed in cells with defective Nbs1 function and is consistent with recent
      observations identifying NFBD1/MDC1 as a component of the Mre11-Rad50-Nbs1
      protein complex. In cells with wild-type Nbs1, suppression of 53BP1 expression
      had no effect on ATM activation but was associated with increased recruitment of
      NFBD1/MDC1 and Nbs1 to sites of DNA breaks, suggesting that decreased 53BP1
      function might be compensated for by increased NFBD1/MDC1 and Nbs1 activity.
      Indeed, in cells with mutant Nbs1, suppression of 53BP1 led to decreased ATM
      activation and phosphorylation of ATM substrates. We conclude that DNA DSBs
      activate ATM through at least two independent pathways involving 53BP1 and
      NFBD1/MDC1-Nbs1, respectively.

PMID- 14695168
TI  - Activating transcription factor 4 increases the cisplatin resistance of human
      cancer cell lines.
AB  - Resistance to cisplatin is a major problem in the treatment of solid tumors. To
      investigate the determinants of cisplatin resistance, we have identified
      cisplatin-inducible genes by differential display of mRNA. One of the cisplatin
      inducible genes was identified as activating transcription factor 4 (ATF4).
      Northern blot analysis demonstrated that expression of ATF4 is inducible at the
      transcriptional level. Its expression is also up-regulated in two cisplatin
      resistant cell lines. We tested whether cellular levels of ATF4 are responsible
      for cisplatin sensitivity by examining 11 human lung cancer cell lines.
      Expression of ATF4 was found to correlate with cisplatin sensitivity (P = 0.01).
      We also evaluated the cisplatin sensitivity of two stable transfectants
      overexpressing ATF4. Both were less sensitive to cisplatin than the parental
      cells but equally sensitive to vincristine. Our findings suggest that levels of
      ATF4 expression could help to predict cisplatin sensitivity.

PMID- 14695169
TI  - Evaluation of Fanconi Anemia genes in familial breast cancer predisposition.
AB  - Fanconi Anemia (FA) is an autosomal recessive syndrome characterized by
      congenital abnormalities, progressive bone marrow failure, and susceptibility to
      cancer. FA has eight known complementation groups and is caused by mutations in
      at least seven genes. Biallelic BRCA2 mutations were shown recently to cause FA
      D1. Monoallelic (heterozygous) BRCA2 mutations confer a high risk of breast
      cancer and are a major cause of familial breast cancer. To investigate whether
      heterozygous variants in other FA genes are high penetrance breast cancer
      susceptibility alleles, we screened germ-line DNA from 88 BRCA1/2-negative
      families, each with at least three cases of breast cancer, for mutations in
      FANCA, FANCC, FANCD2, FANCE, FANCF, and FANCG. Sixty-nine sequence variants were
      identified of which 25 were exonic. None of the exonic variants resulted in
      translational frameshifts or nonsense codons and 14 were polymorphisms documented
      previously. Of the remaining 11 exonic variants, 2 resulted in synonymous
      changes, and 7 were present in controls. Only 2 conservative missense variants, 1
      in FANCA and 1 in FANCE, were each found in a single family and were not present
      in 300 controls. The results indicate that FA gene mutations, other than in
      BRCA2, are unlikely to be a frequent cause of highly penetrant breast cancer
      predisposition.

PMID- 14695170
TI  - Additive interaction of oxaliplatin and 17-allylamino-17-demethoxygeldanamycin in
      colon cancer cell lines results from inhibition of nuclear factor kappaB
      signaling.
AB  - Elucidation of the mechanism by which oxaliplatin induces cell death is essential
      to enhancing its action. We investigated the effects of oxaliplatin and 17
      allylamino-17-demethoxygeldanamycin (17-AAG) in a panel of four colon
      adenocarcinoma cell lines. Cytotoxicity assays demonstrated at least additivity
      in three of the cell lines. Activation of the c-Jun NH(2)-terminal kinase pathway
      by oxaliplatin does not determine cytotoxicity. Activation of p38 was shown to be
      a key proapoptotic mediator of oxaliplatin-induced cell death. Modulation of
      extracellular signal-regulated kinase and AKT signaling had no impact on
      oxaliplatin toxicity in these cells. Nuclear factor (NF)-kappaB was
      constitutively active in all of the cell lines and was inhibited by 17-AAG. Down
      regulation of NF-kappaB transactivation by pharmacological inhibitors enhanced
      oxaliplatin cytotoxicity. These data support an interaction between 17-AAG and
      components of the NF-kappaB pathway in the modulation of oxaliplatin sensitivity
      in colon cancer cells.

PMID- 14695171
TI  - Epigenetic inactivation of CHFR and sensitivity to microtubule inhibitors in
      gastric cancer.
AB  - Mitotic checkpoints prevent errors in chromosome segregation that can lead to
      neoplasia. Therefore, it is notable that gastric cancers often show impaired
      checkpoint function. In the present study, we examined the functional
      consequences of epigenetic inactivation of the mitotic checkpoint gene CHFR in
      gastric cancers. CHFR expression was silenced by DNA methylation of the 5' region
      of the gene in 20% of the gastric cancer cell lines tested and in 39% of primary
      gastric cancers; expression could be restored by treatment with 5-aza-2'
      deoxycytidine, a methyltransferase inhibitor. In addition, histones H3 and H4
      were found to be deacetylated in cell lines showing aberrant methylation,
      indicating a role for histone deacetylation in the methylation-dependent gene
      silencing. Cells not expressing CHFR showed impaired checkpoint function, which
      led to nuclear localization of cyclin B1 after treatment with docetaxel or
      paclitaxel, two microtubule inhibitors. Apparently, the absence of CHFR is
      associated with sensitivity of cells to mitotic stress caused by microtubule
      inhibition, and restoration of CHFR expression by 5-aza-2'-deoxycytidine or
      adenoviral gene transfer restored the checkpoint. By affecting mitotic checkpoint
      function, CHFR inactivation likely plays a key role in tumorigenesis in gastric
      cancer. Moreover, the aberrant methylation of CHFR appears to be a good molecular
      marker with which to predict the sensitivity of gastric cancers to microtubule
      inhibitors.

PMID- 14695172
TI  - Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive
      characterization and comparison of the transcription profiles obtained from three
      major technologies.
AB  - When using gene expression profiling to understand human tumors, one is often
      confronted with long lists of genes that need to be further categorized into
      meaningful data. We performed a comprehensive evaluation and comparison of gene
      expression profiles obtained from pancreatic cancers to determine those genes
      most differentially expressed and thus with the most promise for translation into
      clinically useful targets. cDNA was prepared from 50 samples of normal pancreas
      or duodenal mucosal tissues, 7 samples of chronic pancreatitis, and 39 samples of
      pancreas cancer tissues or cancer cell lines and hybridized to the complete
      Affymetrix Human Genome U133 GeneChip set (arrays U133A and U133B) for
      simultaneous analysis of 45,000 fragments corresponding to 33,000 known genes and
      6,000 expressed sequence tags. Genes expressed at levels at least 3-fold greater
      in the pancreatic cancers as compared with nonneoplastic tissues were identified.
      Three hundred seventy-seven Affymetrix fragments were identified as having > or =
      3-fold expression levels in pancreas cancer specimens as compared with
      nonneoplastic tissues, corresponding to 234 known genes. Serial analysis of gene
      expression libraries (http://www.ncbi.nlm.nih.gov/SAGE/) of two normal pancreatic
      ductal cell cultures (HX and H126) were used to exclude 17 genes with high
      expression levels in the normal duct epithelium (more than five tags/library). Of
      the remaining 217 known genes, 75 have been previously reported as highly
      expressed in pancreatic cancers, while the remaining 142 genes are novel. We used
      principal components analysis (PCA) to identify the genes among these 217
      identified as the most differentially expressed and specific to pancreatic cancer
      tissues or cell lines. Among the most differentially expressed genes identified
      by PCA were Mesothelin, Muc4, Muc5A/C, Kallikrein 10, Transglutaminase 2, Fascin,
      TMPRSS3 and stratifin. The differential expression identified by PCA for these
      genes indicates they are among the more attractive targets for novel therapeutic
      targets, tumor markers, or as a means of screening pancreatic cancer samples for
      information regarding tumor classification or potential therapeutic responses.
      Our findings were also compared in detail to the previously reported findings of
      highly expressed genes in other studies of global gene expression in pancreatic
      cancers. We found that robust changes in gene expression were most often
      identified by more than one gene expression platform. Forty genes were identified
      by more than one method (U133 oligonucleotide arrays, cDNA arrays or serial
      analysis of gene expression), and 6 of these genes were identified by all three
      methods. Our findings identify a novel set of genes as highly expressed in
      pancreatic cancer, validate the differential expression of previously reported
      genes, and provide additional support for those genes most differentially
      expressed to be translated into clinically useful targets.

PMID- 14695173
TI  - Methylation of cytochrome P4501A1 promoter in the lung is associated with tobacco
      smoking.
AB  - Cytochrome P4501A1 (CYP1A1), which is involved in the metabolic activation of
      polycyclic aromatic hydrocarbon procarcinogens derived from tobacco smoke, is
      induced in the lung up to 100-fold because of tobacco smoking. Our aim was to
      study whether promoter methylation has any role in the smoking-associated
      expression of CYP1A1 in human lung. Methylation of CpG sites up to 1.4 kb
      upstream of CYP1A1 gene was studied first by sequencing. Because methylation was
      observed between nucleotides -1400 and -1000, a methylation-specific single
      strand conformational polymorphism method was designed for the region between
      nucleotides -1411 and -1295 that contains five potential methylation sites, one
      of them at the xenobiotic responsive element core sequence. Single-strand
      conformational polymorphism was used on DNA from normal lung samples and
      peripheral WBCs of smokers and nonsmokers, and on human lung adenocarcinoma
      (A549) and bronchial epithelial (Beas-2B) cell lines. In lung tissue complete or
      partial methylation occurred in 33% of heavy smokers (>15 cigarettes/day, n =
      30), 71% of light smokers (< or =15 cigarettes/day or quitted 1-7 days earlier, n
      = 42), and in 98% of nonsmokers (never and ex-smokers, n = 49). Methylation was
      found to increase in 1-7 days after quitting smoking. In active smokers the lack
      of methylation in the studied region of CYP1A1 promoter was associated with a
      slightly higher pulmonary 7-ethoxyresorufin O-deethylase activity in the
      regression models allowing for the daily tobacco consumption and age. No
      association was observed in WBC between methylation and tobacco smoking. In lung
      derived cell lines the methylation remained stable regardless of induction with
      benzo(a)pyrene, but a higher induction was observed in Beas-2B cells, which also
      had less methylation than A549 cells. The association of tobacco smoking with
      CYP1A1 methylation in the lung suggests that promoter methylation is involved in
      the regulation of CYP1A1 induction in vivo.

PMID- 14695174
TI  - An opposing view on WWOX protein function as a tumor suppressor.
AB  - WW domain-containing oxidoreductase (WWOX) is a candidate tumor suppressor gene.
      Because mutation or deletion in the coding region of WWOX is rarely found, it is
      speculated that the appearance of aberrant transcripts affects progression of
      various cancers. However, little is known about the role in these cancers of the
      WWOX protein. To characterize endogenous WWOX proteins, we analyzed WWOX
      expression using newly generated monoclonal antibodies. In immunoblot analysis of
      49 cancer cell lines, only the normal form of the protein was detectable,
      although some of cell lines exhibited aberrant WWOX RNA transcripts. Accumulation
      of truncated proteins was observed by inhibiting proteasomal degradation with MG
      132, whereas expression level of normal protein did not change, suggesting
      truncated proteins may be subjected to rapid degradation through proteasomal
      machinery. Immunohistochemistry for cancer cells demonstrated that WWOX protein
      levels are not decreased but rather elevated in gastric and breast carcinoma,
      challenging the notion of WWOX as a classical tumor suppressor. In noncancerous
      cells, WWOX was observed only in epithelial cells, including hormone-regulated
      cells such as Leydig cells, follicular cells, prostate epithelium, and mammary
      glands. Interestingly, restricted staining in nuclei was observed in some mammary
      gland cells while other epithelial cells exhibited localization of WWOX in
      cytoplasm. Nuclear localization of WWOX was also confirmed in confluent human
      fibroblast KMS-6, whereas WWOX was associated mainly with mitochondria before
      reaching confluence, indicating that WWOX shuttles between cytoplasm and nuclei.
      These findings provide novel insights into aspects of human WWOX function in both
      normal and malignant cells.

PMID- 14695175
TI  - Karyotypic complexity of the NCI-60 drug-screening panel.
AB  - We used spectral karyotyping to provide a detailed analysis of karyotypic
      aberrations in the diverse group of cancer cell lines established by the National
      Cancer Institute for the purpose of anticancer drug discovery. Along with the
      karyotypic description of these cell lines we defined and studied karyotypic
      complexity and heterogeneity (metaphase-to-metaphase variations) based on three
      separate components of genomic anatomy: (a) ploidy; (b) numerical changes; and
      (c) structural rearrangements. A wide variation in these parameters was evident
      in these cell lines, and different association patterns between them were
      revealed. Analysis of the breakpoints and other specific features of chromosomal
      changes across the entire set of cell lines or within particular lineages pointed
      to a striking lability of centromeric regions that distinguishes the epithelial
      tumor cell lines. We have also found that balanced translocations are as frequent
      in absolute number within the cell lines derived from solid as from hematopoietic
      tumors. Important similarities were noticed between karyotypic changes in cancer
      cell lines and that seen in primary tumors. This dataset offers insights into the
      causes and consequences of the destabilizing events and chromosomal instability
      that may occur during tumor development and progression. It also provides a
      foundation for investigating associations between structural genome anatomy and
      cancer molecular markers and targets, gene expression, gene dosage, and
      resistance or sensitivity to tens of thousands of molecular compounds.

PMID- 14695176
TI  - Identification of clinically relevant genes on chromosome 11 in a functional
      model of ovarian cancer tumor suppression.
AB  - Microcell-mediated transfer of normal chromosome 11 (chr 11) to a clonal
      derivative of the ovarian cancer cell line, OVCAR3, was performed and generated
      independent hybrids with a common set of phenotypes: inhibition of cell growth
      and of cellular migration in vitro; and inhibition of tumor growth in vivo.
      Differential display reverse transcriptase-PCR (RT-PCR), cDNA-representational
      difference analysis, and hybridization of cDNA high-density filter arrays
      identified altered mRNAs associated with these phenotypic alterations.
      Quantitative RT-PCR-based validation of each altered mRNA eliminated false
      positives to identify a reduced set of expression differences. Twelve products
      were confirmed as up-regulated and 4 as down-regulated upon introduction of chr
      11. Strikingly, 4 of the 12 up-regulated genes were located on chr 11. Expression
      analysis of selected products by quantitative RT-PCR in a series of 18 human
      primary ovarian tumors revealed several associations with clinicopathological
      features. Importantly, low expression of two products, the lysosomal protease
      CTSD and the lens crystallin CRYAB, was significantly associated with adverse
      patient survival. Immunohistochemical analysis of CTSD in a larger independent
      panel of 58 primary ovarian tumors confirmed that low CTSD was associated with
      poor survival. Furthermore, low CTSD was significantly associated with serous
      histology and advanced tumor stage. The combined approach of microcell-mediated
      chromosome transfer and expression difference analysis has identified several
      altered mRNAs in a model of chr 11-mediated ovarian tumor suppression. The
      detailed contextual characterization of these genes will determine the extent of
      their involvement in neoplastic development.

PMID- 14695177
TI  - BCL2 accelerates inflammation-induced BALB/c plasmacytomas and promotes novel
      tumors with coexisting T(12;15) and T(6;15) translocations.
AB  - Previous studies on peritoneal plasmacytomas (PCTs) in BALB/c (C) mice suggested
      that the enforced expression of the death repressor BCL2 in B cells might
      facilitate the malignant transformation of aberrant B cells containing Myc
      activating T(12;15) translocations, generating an improved model of
      plasmacytomagenesis. To investigate this hypothesis, we backcrossed a human BCL2
      transgene onto strain C and performed a PCT induction study with pristane in the
      newly generated C.BCL2 congenics. In specific pathogen-free-maintained C.BCL2
      mice, PCT incidence (19 of 34, 56%) was 24 times higher than in specific pathogen
      free-maintained C mice (1 of 44, 2.3%), and tumor onset (113 days) was half that
      of conventionally maintained C mice (220 days). BCL2 transgenic PCT harbored
      T(12;15) translocations (12 of 12 tumors) with an unusual clustering of
      translocation breakpoints in the near 5' flank of Myc (4 of 5 tumors, 80%). Five
      tumors contained coexisting T(12;15) and T(6;15) translocations (not observed in
      >300 karyotyped PCTs from conventionally maintained C mice). BCL2 transgenic
      C57BL/6 mice exclusively developed B lymphomas (11 of 20, 55%) that also
      contained T(12;15) translocations (11 of 11 cases) with breakpoints in the near
      5' flank of Myc (five of five tumors). We conclude that BCL2 accelerates PCT with
      novel Myc-activating translocations independently of environmental antigen
      stimulation. Accelerated plasmacytomagenesis in strain C.BCL2 may be useful for
      designing and testing BCL2 inhibition strategies in human plasma cell tumors
      overexpressing BCL2, such as Waldenstrom's macroglobulinemia and multiple
      myeloma.

PMID- 14695178
TI  - Switching mechanisms of cell death in mdm2- and mdm4-null mice by deletion of p53
      downstream targets.
AB  - The p53 tumor suppressor ensures maintenance of genome integrity by initiating
      either apoptosis or cell cycle arrest in response to DNA damage. Deletion of
      either mdm2 or mdm4 genes, which encode p53 inhibitors, results in embryonic
      lethality. The lethal phenotypes are rescued in the absence of p53, which
      indicates that increased activity of p53 is the cause of lethality in the mdm2-
      and mdm4-null embryos. Here we show that mdm2-null embryos die because of
      apoptosis initiated at 3.5 days postcoitum (dpc). Partial rescue of mdm2-null
      embryos by deletion of bax allows survival to 6.5 dpc and alters the mechanism of
      death from apoptosis to cell cycle arrest, indicating that bax is a critical
      component of the p53 pathway in early embryogenesis. The death of mdm4-null
      embryos is due to p53-initiated cell cycle arrest at 7.5 dpc. Deletion of
      p21(p21(waf1/cip1)), a p53 downstream target partially responsible for cell cycle
      arrest, does not rescue this phenotype; however, deletion of p21 alters the
      mechanism of cell death from lack of proliferation to apoptosis. Thus, in both
      examples, deletion of a p53 downstream target gene allows p53 to redirect its
      efforts, highlighting a high degree of plasticity in p53 function.

PMID- 14695179
TI  - Inactivation of wild-type p53 protein function by reactive oxygen and nitrogen
      species in malignant glioma cells.
AB  - Malignant gliomas are the most common primary brain tumors in adults, and the
      most malignant form, glioblastoma multiforme (GBM), is usually rapidly fatal.
      Most GBMs do not have p53 mutations, although the p53 tumor suppressor pathway
      appears to be inactivated. GBMs grow in a hypoxic and inflammatory
      microenvironment, and increased levels of the free radicals nitric oxide (NO) and
      superoxide () occur in these malignancies in vivo. Peroxynitrite (ONOO(-)) is a
      highly reactive molecule produced by excess NO and that can posttranslationally
      modify and inactivate proteins, especially zinc finger transcription factors such
      as p53. We demonstrated previously that GBMs have evidence of tyrosine nitration,
      the "footprint" of peroxynitrite-mediated protein modification in vivo, and that
      peroxynitrite could inhibit the specific DNA binding ability of wild-type p53
      protein in glioma cells in vitro. Here we show that both authentic peroxynitrite
      and SIN-1 (3-morpholinosydnonimine hydrochloride), a molecule that decomposes
      into NO and to form peroxynitrite, can inhibit wild-type p53 function in
      malignant glioma cells. Concentrations of peroxynitrite associated with a tumor
      inflammatory environment caused dysregulation of wild-type p53 transcriptional
      activity and downstream p21(WAF1) expression.

PMID- 14695180
TI  - Hepatocyte growth factor activator inhibitor 2/placental bikunin (HAI-2/PB) gene
      is frequently hypermethylated in human hepatocellular carcinoma.
AB  - To identify methylation-mediated silencing of genes in hepatocellular carcinoma
      (HCC), we surveyed genes induced by treatment with 5-aza-2'-deoxycytidine (5-Aza
      CdR) in six human hepatoma cell lines using cDNA microarray analysis and
      determined the methylation status of 5' CpG islands by bisulfite DNA sequencing
      or methylation-specific PCR. Fifty genes exhibited a >5-fold induction in
      response to treatment with 5-Aza-CdR in at least one of the hepatoma cell lines
      examined. Among these genes, the hepatocyte growth factor activator inhibitor
      2/placental bikunin (HAI-2/PB) gene was maximally induced by 5-Aza-CdR in three
      of six cell lines studied (HLE, HuH7, and Hep3B). Bisulfite sequencing revealed
      that the 5' CpG island of this gene was densely methylated in HLE, HuH7, and
      Hep3B cells. After treatment with 5-Aza-CdR, re-expression and demethylation of
      HAI-2/PB gene were detected in these cells. These findings suggest that HAI-2/PB
      expression may be inappropriately repressed by promoter hypermethylation in HCC.
      Methylation-specific PCR analysis demonstrated that HAI-2/PB hypermethylation
      occurred in 21 of 26 HCC tumors (80.8%), whereas in the corresponding nontumorous
      liver tissues, it was found in 7 of 26 samples (26.9%). In addition, HAI-2/PB
      hypermethylation was not detected in any of the seven normal liver samples from
      individuals without HCC. Reverse transcription-PCR analysis demonstrated that
      promoter hypermethylation was associated with the reduced expression of the HAI
      2/PB gene in HCC tumors. In conclusion, we have found that the HAI-2/PB gene is
      silenced by promoter hypermethylation in human hepatoma cells by means of cDNA
      microarray analysis after 5-Aza-CdR treatment, and that HAI-2/PB hypermethylation
      occurs frequently in primary HCC tumors.

PMID- 14695181
TI  - Epigenetic regulation of coxsackie and adenovirus receptor (CAR) gene promoter in
      urogenital cancer cells.
AB  - Coxsackie and adenovirus receptor (CAR) is not only a high-affinity receptor for
      adenovirus, but also a tumor inhibitor in both prostate and bladder cancer lines.
      Decreased CAR gene expression is often detected in cancer specimens; however, the
      mechanism(s) is still unknown. In this study, we cloned the entire CAR gene and
      characterized the core promoter sequence of the CAR gene. The CAR gene promoter
      activity correlated with the differential expression of CAR mRNA levels from
      several urogenital cancer cell lines, indicating that the down-regulation of CAR
      gene expression is mediated by transcriptional regulation. It is known that
      epigenetic control, such as DNA methylation and histone acetylation of chromatin
      structure, dictates gene expression. Data from this study indicate that the
      activation of the CAR gene promoter is modulated by histone acetylation, but not
      by DNA methylation, in urogenital cancer cells. Also, a potent cancer
      chemotherapeutic agent (FR901228), a histone deacetylase inhibitor, was able to
      induce endogenous CAR gene expression in several urogenital cancer cells. Taken
      together, epigenetic control of CAR gene underlies the down-regulation of this
      gene in urogenital cancers.

PMID- 14695182
TI  - Notch1 can contribute to viral-induced transformation of primary human
      keratinocytes.
AB  - The human papillomavirus (HPV) is the most significant causative agent in the
      development of cervical cancer. Despite its presence in almost all cervical
      cancers, HPV by itself is unable to transform a normal cell to a cancerous one.
      Instead, additional cellular mutations are required to supplement the HPV
      oncoproteins E6 and E7. Activation of the Notch1 signaling pathway has been
      proposed as one of the cellular changes that cooperate with the E6 and E7
      proteins to cause cervical cancers. This proposition is based on: (a) the
      detection of active Notch1 in high-grade cervical lesions and cancers; (b) the
      synergism between Notch1 and E6 and E7 to transform immortalized cells; and (c)
      the obliteration of neoplastic properties of a cervical cancer cell line when
      Notch1 expression was inhibited. However, this view was put in doubt by a recent
      report that showed Notch1 expression is markedly reduced in cervical cancer
      cells, and this was attributed to the ability of Notch1 to repress the expression
      of the HPV E6 and E7 proteins. Here we report that although exaggerated levels of
      Notch1 can, indeed, adversely affect HPV E6 and E7 expression, and cellular
      proliferation in general, moderate levels of Notch1, together with active
      phosphoinositide 3 kinase, can, instead, exhibit oncogenic properties that
      transform primary cells containing HPV16 E6 and E7 proteins. In addition, we show
      that activated Notch1 is readily detected in all cervical cancer cell lines
      tested. Together, these results show that not only do cervical cancer cells
      express Notch1, but also that Notch1 signaling, in synergy with other cellular
      changes, can participate in the transformation of primary cells expressing E6 and
      E7 proteins.

PMID- 14695183
TI  - Promoter hypermethylation of tumor suppressor genes in urine from kidney cancer
      patients.
AB  - Kidney cancer confined by the renal capsule can be surgically cured in the
      majority of cases, whereas the prognosis for patients with advanced disease at
      presentation remains poor. Novel strategies for early detection are therefore
      needed. Molecular DNA-based tests have successfully used the genetic alterations
      that initiate and drive tumorigenesis as targets for the early detection of
      several types of cancer in bodily fluids, including urine. Using sensitive
      methylation-specific PCR, we screened matched tumor DNA and sediment DNA from
      preoperative urine specimens obtained in 50 patients with kidney tumors,
      representing all major histological types, for hypermethylation status of a panel
      of six normally unmethylated tumor suppressor genes VHL, p16/CDKN2a, p14ARF, APC,
      RASSF1A, and Timp-3. Hypermethylation of at least one gene was found in all 50
      tumor DNAs (100% diagnostic coverage) and an identical pattern of gene
      hypermethylation found in the matched urine DNA from 44 of 50 patients (88%
      sensitivity), including 27/30 cases of stage I disease. In contrast,
      hypermethylation of the genes in the panel was not observed in normal kidney
      tissue or in urine from normal healthy individuals and patients with benign
      kidney disease (100% specificity). Hypermethylation of VHL was found only in
      clear cell, whereas hypermethylation of p14ARF, APC, or RASSF1A was more frequent
      in nonclear cell tumors, which suggested that the panel might facilitate
      differential diagnosis. We conclude that promoter hypermethylation is a common
      and early event in kidney tumorigenesis and can be detected in the urine DNA from
      patients with organ-confined renal cancers of all histological types. Methylation
      specific PCR may enhance early detection of renal cancer using a noninvasive
      urine test.

PMID- 14695184
TI  - Phorbol ester stimulates the nonhypoxic induction of a novel hypoxia-inducible
      factor 1alpha isoform: implications for tumor promotion.
AB  - Hypoxia-inducible factor-1 (HIF-1), which is present at higher levels in human
      tumors, plays important roles in tumor promotion. It is composed of HIF-1alpha
      and HIF-1beta subunits and its activity depends on the amount of HIF-1alpha,
      which is tightly controlled by cellular oxygen tension. In addition to hypoxia,
      various nonhypoxic stimuli can stabilize HIF-1alpha in tumor cells, implying that
      both hypoxic and nonhypoxic stimuli contribute to the overexpression of HIF
      1alpha in tumors. On the other hand, phorbol esters such as phorbol-12-myristate
      13-acetate (PMA) are known to be potent tumor promoters. Here, we identified a
      novel HIF-1alpha isoform, which is regulated primarily by PMA. The variant mRNA
      lacks exon 11 and produces a 785-amino acid isoform (HIF-1alpha(785)) without
      altering the reading frame and therefore the COOH-terminal transcriptional
      activity. HIF-1alpha(785) is induced markedly by PMA and heat shock, the latter
      of which is also known to induce HIF-1alpha. HIF-1alpha(785) escapes from lysine
      acetylation because of the loss of Lys(532) and was stabilized under normoxic
      conditions. Its expression was blocked by reducing agents and by a mitogen
      activated protein/extracellular signal-regulated kinase-1 inhibitor and enhanced
      by hydrogen peroxide. In addition, HIF-1alpha(785) overexpression strikingly
      enhanced tumor growth in vivo. These results suggest that HIF-1alpha(785) is
      induced by PMA under normoxic conditions via a redox-dependent mitogen-activated
      protein/extracellular signal-regulated kinase-1 pathway and that it plays an
      important role in tumor promotion.

PMID- 14695185
TI  - Enhancement of the mutagenicity of benzo(a)pyrene diol epoxide by a nonmutagenic
      dose of ultraviolet A radiation.
AB  - We investigated the effects of single and combined exposures to two ubiquitous
      environmental carcinogens, polycyclic aromatic hydrocarbons and UVA radiation, in
      Big Blue mouse embryonic fibroblasts. We quantified the cytotoxicity, DNA adduct
      formation, and induction of mutations in the cII transgene in cells treated with
      a single agent or combinations of agents in both direct and reverse order.
      Mapping of DNA adducts by terminal transferase-dependent PCR showed the
      preferential formation of bulky adducts at identical nucleotide positions along
      the cII gene after treatment with the prototype polycyclic aromatic hydrocarbon,
      benzo(a)pyrene diol epoxide [B(a)PDE], or B(a)PDE plus UVA radiation treatments
      but not after UVA irradiation alone. The cII mutant frequency determined by a
      lambda phage-based mutation detection system was not increased significantly by
      UVA irradiation (1.7-fold over background; P < 0.3); however, B(a)PDE alone or in
      combinations with UVA radiation significantly increased the cII mutant frequency
      (P < 0.001). The highest cII mutant frequency was induced by the treatment with
      B(a)PDE followed by UVA irradiation, which was more than the added mutant
      frequencies of the two agents individually (>12.2-fold versus <7.6-fold over
      background; P < 0.01). In support of these findings, DNA sequencing analyses
      showed that the mutational spectra induced by B(a)PDE alone or combined with UVA
      radiation were significantly different from those derived spontaneously (P <
      0.0001) or by UVA irradiation (P < 0.0005). The signature of mutations produced
      by B(a)PDE i.e., "G-->T + C-->A" transversions, was significantly enhanced when
      the B(a)PDE treatment was followed by UVA irradiation (47% versus 65%; P < 0.01).
      Also, the methylated CpG dinucleotide-targeted overall mutations specifically
      induced by B(a)PDE were increased after the subsequent UVA irradiation (43%
      versus 51%, respectively). Such enhancements in the mutational signature of
      B(a)PDE were most pronounced within the preferential DNA adduction sites along
      the cII gene after the treatment with B(a)PDE plus UVA radiation, which suggests
      that the primary B(a)PDE adducts are converted to more mutagenic species on UVA
      irradiation. We conclude that UVA radiation at a nonmutagenic dose has an
      enhancing effect on the mechanism by which B(a)PDE induces mutations.

PMID- 14695186
TI  - ATM haplotypes and cellular response to DNA damage: association with breast
      cancer risk and clinical radiosensitivity.
AB  - The ATM gene, mutated in the cancer-prone and radiation-sensitive syndrome ataxia
      telangiectasia (AT), could predispose to breast cancer (BC) development and
      adverse radiotherapy responses. Sixteen ATM variants were genotyped in 254 BC
      cases, 70 of whom were adverse radiotherapy responders (RS-BC), and 312 control
      subjects and the ATM haplotypes were constructed. Constitutive ATM protein, cell
      survival, and the p53 response after exposure to ionizing radiation were compared
      in lymphoblastoid cell lines (LCLs) established from the BC cases, AT, and normal
      individuals. The tightly linked intronic ATM polymorphisms IVS22-77 T>C and IVS48
      + 238 C>G, in the homozygote state were associated with increased BC risk [IVS22
      77 CC versus TT odds ratio (OR), 1.67; 95% confidence interval (CI), 1.00-2.81],
      and in the heterozygote state with clinical radioprotection (IVS22-77 CT versus
      TT OR, 0.45; 95% CI, 0.24-0.85). Homozygote carriers of the G5557A variant were
      over-represented in RS-BC cases compared with non-RS-BC cases (OR, 6.76; 95% CI,
      1.19-38.43). These three single nucleotide polymorphisms were associated with the
      three major ATM haplotypes present in >80% of the study population. BC LCLs
      treated with ionizing radiation exhibited an intermediate cell survival and p53
      response between that of normal and AT LCLs, with the response in the RS-BC LCLs
      being more compromised than in the non-RS-BC LCLs. Our study suggests a general
      pattern of increased BC risk associated with carrying any one of the ATM variants
      studied, with a significant association being observed in individuals carrying
      variants on both ATM alleles (OR, 1.75; 95% CI, 1.09-2.81) and that ATM variants
      may impact on radiation sensitivity.

PMID- 14695187
TI  - TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor
      target gene induction via effects on chromatin remodeling.
AB  - Beta-catenin has a key role in Wnt signaling via effects on T-cell factor (TCF)
      mediated transcription. Mutational defects in beta-catenin regulation are seen in
      many cancers, leading to elevated beta-catenin levels, enhanced binding of beta
      catenin to TCFs, and increased expression of TCF-regulated genes. Factors
      cooperating with beta-catenin in transcription of TCF-regulated genes are not
      well defined. TIP49, an ATPase previously implicated as a cofactor for oncogenic
      transformation by c-Myc, has been shown to bind to beta-catenin. We found that
      expression of an ATPase-deficient mutant form of TIP49 (TIP49D302N) substantially
      inhibited beta-catenin-mediated neoplastic transformation of immortalized rat
      epithelial cells and anchorage-independent growth of human colon cancer cells
      with deregulated beta-catenin. The TIP49D302N mutant inhibited beta-catenin
      mediated activation of TCF-dependent cellular genes. Similar inhibition of the
      expression of beta-catenin/TCF-dependent genes was seen with small interfering
      RNA approaches against endogenous TIP49. TIP49 was found in complexes with
      chromatin remodeling and histone-modifying factors and cofactors, including the
      TIP60 histone acetylase-associated proteins transactivation/transformation-domain
      associated protein (TRRAP) and BAF53. Using chromatin immunoprecipitation
      methods, the TIP49, TIP60, and TRRAP proteins were found to interact with
      sequences in the regulatory region of the gene for ITF-2, a TCF-dependent
      cellular gene. The ability of TIP49D302N to inhibit ITF-2 gene expression was
      linked to decreased acetylation of histones in the vicinity of the TCF-binding
      sites in the ITF-2 promoter region. We suggest that TIP49 is an important
      cofactor in beta-catenin/TCF gene regulation in normal and neoplastic cells,
      likely functioning in chromatin remodeling.

PMID- 14695188
TI  - An endogenous retrovirus derived from human melanoma cells.
AB  - We show that human melanoma cells produce retrovirus-like particles that exhibit
      reverse transcriptase activity, package sequences homologous to human endogenous
      retrovirus K (HERV-K), and contain mature forms of the Gag and Env proteins. We
      also demonstrate expression of the pol gene and of Gag, Env, and Rec proteins in
      human melanomas and metastases but not in melanocytes or normal lymph nodes. The
      data suggest that expression of retroviral genes and production of retroviral
      particles is activated during development of melanoma.

PMID- 14695189
TI  - Tamoxifen inhibits secretion of vascular endothelial growth factor in breast
      cancer in vivo.
AB  - Vascular endothelial growth factor (VEGF) is considered a key mediator of tumor
      angiogenesis, including neovascularization in human breast cancer. High tissue
      VEGF levels appear to correlate with poor prognosis and decreased overall
      survival in node-positive and node-negative breast cancer patients. Hormonal
      regulation of VEGF expression has been demonstrated, and some reports indicate
      that tamoxifen, a partial estrogen receptor agonist, increases VEGF mRNA in
      breast cancer cells. These results appear to contradict the efficacy of tamoxifen
      as an adjuvant for estrogen-dependent breast cancer, yet clinical data show that
      tamoxifen prevents metastasis and increases overall survival. In this study, we
      confirmed previous studies showing that intracellular levels of VEGF in vitro
      increased in response to tamoxifen to levels similar to those observed after
      estrogen treatment. To further study hormonal effects on the release of VEGF, we
      used microdialysis to sample the extracellular space, where VEGF is biologically
      active, in solid tumors in situ. We show for the first time that tamoxifen
      decreased extracellular VEGF in vivo in solid MCF-7 tumors in nude mice. These in
      vivo findings were confirmed in vitro where extracellular VEGF in the cell
      culture medium was decreased significantly by tamoxifen treatment. Furthermore,
      we illustrate that microdialysis is a viable method that may be applied in human
      breast tissue to detect soluble VEGF in situ released by the tumor.

PMID- 14695190
TI  - High heparanase activity in multiple myeloma is associated with elevated
      microvessel density.
AB  - Heparanase is an enzyme that cleaves heparan sulfate chains of proteoglycans, and
      its expression has been associated with increased growth, metastasis, and
      angiogenesis of some tumors. Because myeloma tumor cells express high levels of
      the syndecan-1 heparan sulfate proteoglycan and because these tumors grow as
      highly vascularized aggregates within the bone marrow, we analyzed the activity,
      expression, and function of heparanase in myeloma patients. Analysis of
      heparanase activity in the plasma isolated from bone marrow biopsies of 100
      patients reveals 86 positive for heparanase activity and 14 negative. The bone
      marrow samples can be further divided into three categories of heparanase
      activity, high activity (42 patients), low activity (44 patients), and negative
      (14 patients). In contrast to the bone marrow plasma, levels of heparanase
      activity in peripheral blood plasma of 29 myeloma patients were either negative
      or low, suggesting that in multiple myeloma, heparanase functions in the local
      microenvironment of the bone marrow and its activity is not significantly
      elevated systemically. Immunohistochemistry reveals that patients with high
      levels of heparanase activity often have tumor cells with intense staining for
      the enzyme. Interestingly, a marked heterogeneity among tumor cells was noted,
      with clusters of heavily stained cells surrounded by cells with weak or negative
      staining for heparanase. Analysis of microvessel density reveals a strikingly
      higher concentration of vessels in patients with high heparanase activity (78.96
      vessels/mm(2)) as compared with patients negative for heparanase activity (25.03
      vessels/mm(2)). When human myeloma cells transfected with the cDNA for heparanase
      are implanted in severe combined immunodeficient (SCID) mice, the resulting
      tumors exhibited a significantly higher microvessel density than did tumors
      established with control cells. Thus, expression of heparanase appears to play a
      direct role in enhancing microvessel density in these myeloma tumors. Because
      heparanase is known to stimulate angiogenesis, and because high microvessel
      density is associated with poor prognosis in myeloma, we conclude that heparanase
      expression likely plays an important role in regulating the growth and
      progression of myeloma, and that therapies designed to block heparanase activity
      may aid in controlling this cancer.

PMID- 14695191
TI  - Activation of signal transducer and activator of transcription 5 is required for
      progression of autochthonous prostate cancer: evidence from the transgenic
      adenocarcinoma of the mouse prostate system.
AB  - The constitutive activation of signal transducer and activator of transcription
      (STAT) proteins has been demonstrated in many diverse human cancer cell lines and
      clinical tumors including prostate cancer. The STAT family has at least seven
      members, and the two forms of the STAT5 protein, STAT5A and STAT5B, exhibit a
      high degree of sequence similarity. We have reported previously that expression
      of STAT5B, but not STAT5A, could enhance the transforming potential of v-src and
      induces cell cycle progression and motility in fibroblasts. In the current study
      we demonstrate specific activation of STAT5B in epithelial cells representing
      invasive and metastatic prostate cancer. We also demonstrate that the naturally
      occurring dominant-negative isoform STAT5DeltaB can block cell cycle progression
      through G(1) and inhibit the growth, invasive potential, and clonogenic ability
      of these prostate cancer cell lines. Furthermore, we report that the dominant
      negative isoform STAT5DeltaB can inhibit the growth of prostate cancer cells in
      grafting studies. These results support our hypothesis that specific activation
      of STAT5, in particular STAT5B, facilitates the progression of prostate cancer.

PMID- 14695192
TI  - TIP30 deficiency increases susceptibility to tumorigenesis.
AB  - TIP30, also called CC3 or Htatip2, is a putative metastasis suppressor that
      promotes apoptosis and inhibits angiogenesis. Although TIP30 has several
      characteristic features of a tumor suppressor in in vitro analyses, tumor
      development as a result of TIP30 inactivation has not been demonstrated in vivo,
      and abnormal expression of TIP30 in human cancer has not been reported. Using
      genetically engineered mice and cells deficient in TIP30, we show that TIP30
      deficient mice have a high incidence of hepatocellular carcinoma and other
      tumors, and loss of TIP30 enhances susceptibility of fibroblasts to
      transformation by the SV40 large T antigen. Furthermore, immunohistochemical
      analysis indicates that reduced TIP30 expression is associated with 33% of human
      hepatocellular carcinomas. Some of these carcinomas harbor missense mutations in
      the Tip30 gene, which cause abnormal expression of TIP30. Together, these results
      demonstrate that the Tip30 gene is a tumor susceptibility gene playing an
      important role in the suppression of hepatocarcinogenesis.

PMID- 14695193
TI  - IG20, a MADD splice variant, increases cell susceptibility to gamma-irradiation
      and induces soluble mediators that suppress tumor cell growth.
AB  - The IG20 gene encodes at least four splice variants, including DENN-SV and IG20.
      DENN-SV is constitutively expressed at higher levels in tumor tissues. Cells
      transfected with the DENN-SV cDNA show increased resistance to tumor necrosis
      factor alpha (TNFalpha), TNF-related apoptosis-inducing ligand (TRAIL),
      etoposide, and vinblastine treatment, whereas overexpression of IG20 enhanced
      susceptibility to both intrinsic (drugs) and extrinsic (e.g., TNFalpha and TRAIL)
      death signals. In this study, we investigated whether expression of the IG20 can
      render cells susceptible to gamma-irradiation. Consistent with previous results,
      overexpression of DENN-SV and IG20 in HeLa cells conferred resistance and
      susceptibility, respectively, to the effects of gamma-irradiation. HeLa IG20 cell
      susceptibility was attributable to enhanced apoptosis and reduced cell growth.
      This growth suppression was mediated by secreted soluble factors. Although HeLa
      DENN-SV cells grew more rapidly than control cells, replenishment with
      conditioned media from HeLa IG20 cells suppressed their growth. In addition, the
      conditioned media from HeLa IG20 cells stopped the growth of ovarian PA-1 cancer
      cells in the G(1)-G(0) cell cycle stage. Among an array of cytokines tested,
      interleukin 6 (IL-6) was found at the highest levels in HeLa IG20 culture
      supernatants, and IL-6 neutralization showed that it was, in part, responsible
      for the cell growth suppression. HeLa IG20 cells had elevated basal nuclear
      factor kappaB levels, a known regulator of IL-6 transcription. Finally, IG20
      overexpression enhanced the combined apoptotic effects of TRAIL and gamma
      irradiation on HeLa cells. These results suggest that understanding further the
      mechanism of action of the IG20 splice variant may help in the advancement of
      cancer therapies.

PMID- 14695194
TI  - Expression of prolyl-hydroxylase-1 (PHD1/EGLN2) suppresses hypoxia inducible
      factor-1alpha activation and inhibits tumor growth.
AB  - Hypoxic stress is one of the major selective pressures in the microenvironment of
      solid tumors, and overcoming this restriction is essential for tumor progression.
      One of the key factors driving the cellular response to lack of oxygen is hypoxia
      inducible factor (HIF), a key transcriptional factor. The level of the alpha
      subunit of HIF-1 is regulated by rapid degradation that is controlled by a family
      of prolyl hydroxylases (PHDs/EGLNs), the activity of which depends on oxygen
      availability. Our study shows that ectopic expression of mPHD1 suppressed
      accumulation of HIF-1alpha and secretion of Vascular Endothelial Growth Factor
      after treatment of cells with a hypoxia-mimetic drug. Furthermore, when colon
      carcinoma cells expressing mPHD1 were injected into nude mice, tumor growth was
      inhibited, and the inhibition of tumor growth was correlated with increased
      necrosis and a striking decrease in microvessel density. These data demonstrate
      that inhibition of hypoxia-induced activation of HIF-1alpha through activation of
      HIF-hydroxylase can provide a novel therapeutic strategy for inhibition of tumor
      growth and neovascularization and support the development of gene transfer
      approaches based on the activation of HIF-prolyl hydroxylases.

PMID- 14695195
TI  - Cooperation between ectopic FGFR1 and depression of FGFR2 in induction of
      prostatic intraepithelial neoplasia in the mouse prostate.
AB  - Disruption of the regulatory communication from the stroma to the epithelium
      mediated by the FGF7/10-FGFR2 signaling axis in the prostate and expression of
      ectopic FGFR1 in prostatic epithelial cells often correlate with prostate cancer
      progression both in human and in experimental animals. Ectopic expression of
      constitutively active FGFR1 mutant (caFGFR1) at low levels in prostate epithelial
      cells induces low- to intermediate-grade prostatic intraepithelial neoplasia
      (PIN) within 6-8 months and high-grade PIN in 20-25 months. Depression of the
      FGFR2 signaling in the prostate also disturbs homeostasis in the prostate and
      induces prostate hyperplasia. To study whether PIN lesions induced by the caFGFR1
      were expression-level dependent, and whether expression of the caFGFR1 and
      depression of the FGFR2 signaling in the prostate synergistically disturbed
      prostate homeostasis, we generated two new strains of ARR2PBi-caFGFR1 transgenic
      mice, which highly expressed caFGFR1 in prostatic epithelial cells. The mice were
      crossed with KDNR mice to generate ARR2PBi-caFGFR1/KDNR bigenic mice. The ARR2PBi
      caFGFR1 mice developed high-grade PIN within 8 months, which was significantly
      faster than the mice expressing caFGFR1 at low levels. In addition, depression of
      the FGFR2 signaling clearly promoted perturbation of cellular homeostasis induced
      by the caFGFR1. The results demonstrated that the PIN development in caFGFR1
      transgenic mice was caFGFR1 dosage-dependent, and indicated that the ectopic
      FGFR1 and the resident FGFR2 in epithelial cells had opposite impacts on
      intercompartmental homeostasis in the prostate. The bigenic mice provide a model
      with cooperative aberrations in the fibroblast growth factor signaling axis for
      evaluation of tumor-initiating events in prostate tumorigenesis.

PMID- 14695196
TI  - Gene expression profiling-based prediction of response of colon carcinoma cells
      to 5-fluorouracil and camptothecin.
AB  - 5-Fluorouracil (5-FU) is the most common chemotherapeutic agent used in the
      treatment of colorectal cancer, yet objective response rates are low. Recently,
      camptothecin (CPT) has emerged as an effective alternative therapy. Decisive
      means to determine treatment, based on the likelihood of response to each of
      these agents, could greatly enhance the management of this disease. Here, the
      ability of cDNA microarray-generated basal gene expression profiles to predict
      apoptotic response to 5-FU and CPT was determined in a panel of 30 colon
      carcinoma cell lines. Genes whose basal level of expression correlated
      significantly with 5-FU- and CPT-induced apoptosis were selected, and their
      predictive power was assessed using a "leave one out" jackknife cross-validation
      strategy. Selection of the 50 genes best correlated with 5-FU-induced apoptosis,
      but not 50 randomly selected genes, significantly predicted response to this
      agent. Importantly, this gene expression profiling approach predicted response
      more effectively than four previously established determinants of 5-FU response:
      thymidylate synthase and thymidine phosphorylase activity; and p53 and mismatch
      repair status. Furthermore, reanalysis of the database demonstrated that
      selection of the 149 genes best correlated with CPT-induced apoptosis maximally
      and significantly predicted response to this agent. These studies demonstrate
      that the basal gene expression profile of colon cancer cells can be used to
      predict and distinguish response to multiple chemotherapeutic agents and
      establish the potential of this methodology as a means by which rational
      decisions regarding choice of therapy can be approached.

PMID- 14695197
TI  - Cyclophosphamide treatment modifies tumor oxygenation and glycolytic rates of RIF
      1 tumors: 13C magnetic resonance spectroscopy, Eppendorf electrode, and redox
      scanning.
AB  - The effect of cyclophosphamide (Cp) on the glycolytic rate of radiation-induced
      fibrosarcomas (RIF-1) was measured in vivo in C3H mice by following the
      production of [3-(13)C]lactate after tail vein infusion of labeled [1
      (13)C]glucose. Cp administered i.p. at a dose of 300 mg/kg caused a significant
      drop in glycolytic rate 24 h after treatment (P < 0.01). This drop was
      accompanied by an increase in [C-3]/[C-4] glutamate ratio in perchloric acid
      extracts of the tumors, indicating an increase in the Kreb's cycle activity.
      Treatment with Cp led to a significant decrease (P < 0.01) in tissue pO(2),
      measured in vivo with an oxygen Eppendorf electrode. Increases in NADH levels
      were also observed in rapidly frozen excised tumors examined by three-dimensional
      optical redox scanning. A significant decrease in tumor pO(2) and an increase in
      the NADH levels are suggestive of an increase in oxygen consumption by these
      tumors after Cp treatment. Overall, these data indicate that the reduction in
      glycolytic rate of Cp-treated RIF-1 tumors is due to an increase in aerobic
      metabolism.

PMID- 14695198
TI  - Regulation of heparanase gene expression by estrogen in breast cancer.
AB  - Numerous epidemiological studies clearly suggest that estrogen is one of the main
      driving forces in breast tumorigenesis, but precise mechanisms of cancer
      promotion by estrogen remain poorly understood. Classically, tumorigenic effects
      of estrogen have been attributed to its ability to directly promote the
      proliferation of breast cancer cells. In addition to abnormal proliferation,
      interactions between tumor cells and surrounding stromal components (e.g.,
      enzymatic remodeling and degradation of extracellular matrix) are critical for
      cancer progression, angiogenesis, and metastasis. We now report that in breast
      carcinomas, estrogen may promote these pathological tumor-stromal interactions
      through up-regulation of heparanase gene expression. Heparanase is an
      endoglycosidase degrading heparan sulfate, of the basement membrane and
      extracellular matrix. This cleavage affects tumor-stromal interaction,
      neovascularization, local invasion, and metastatic spread. However, little is
      known about transcriptional regulation of the heparanase gene. We identified four
      putative estrogen response elements in the heparanase promoter region and found
      that transcription of a luciferase reporter gene driven by the heparanase
      promoter was significantly increased in estrogen-receptor positive MCF-7 human
      breast carcinoma cells after estrogen treatment. Estrogen-induced heparanase mRNA
      transcription in estrogen receptor-positive, but not in estrogen receptor
      negative, breast cancer cells, confirmed the promoter study data. The estrogen
      effects on heparanase mRNA expression levels were abolished in the presence of
      the pure antiestrogen ICI 182,780, indicating that the classic estrogen receptor
      pathway is involved in transcriptional activation of heparanase. In vivo,
      exposure to estrogen augmented levels of heparanase protein in MCF-7 cells
      embedded in Matrigel plugs and correlated with increased plug vascularization.
      Collectively, our data suggest a new molecular pathway through which estrogen,
      independent of its proliferative effect, may induce heparanase overexpression
      and, thus, promote tumor-stromal interactions, critical for breast carcinoma
      development and progression.

PMID- 14695199
TI  - Migration-stimulating factor: a genetically truncated onco-fetal fibronectin
      isoform expressed by carcinoma and tumor-associated stromal cells.
AB  - Migration-stimulating factor (MSF) is a 70-kDa motogenic protein previously
      reported to be expressed by fetal and cancer patient fibroblasts cultured in
      vitro and present in the serum of breast cancer patients. A 2.2-kb full-length
      MSF cDNA has been cloned and shown to be a truncated isoform of fibronectin
      generated from its primary gene transcript by a hitherto unrecognized intron read
      through mechanism. MSF cDNA is identical to the 5' end of fibronectin cDNA, up to
      and including exon III-1a, and terminates in a novel 195-nucleotide 3' sequence.
      This MSF unique sequence is derived from the intron immediately downstream of
      exon III-1a in the fibronectin gene and is not found in any previously identified
      "full-length" fibronectin cDNA. MSF mRNA is 1000-fold less abundant than full
      length fibronectin message in fetal fibroblasts and exhibits rapid biphasic decay
      kinetics previously associated with oncogenes and stress response molecules. MSF
      recombinant protein exhibits a potent and substratum-dependent motogenic
      activity, with half-maximal response manifest at 0.1-1.0 pg/ml. This activity is
      (a) mediated by the IGD amino acid motif; and (b) not expressed by (i.e., cryptic
      within) full-length fibronectin. In situ hybridization and immunohistochemistry
      confirm that MSF is expressed by tumor-associated fibroblasts and additionally
      indicate that it is also expressed by carcinoma cells and tumor-associated
      vascular endothelial cells. MSF, as a consequence of its potent bioactivities and
      expression by both stromal and carcinoma cell populations, is well placed to
      function as an epigenetic effector promoting cancer development.

PMID- 14695200
TI  - Activation of p21-activated kinase 1-nuclear factor kappaB signaling by Kaposi's
      sarcoma-associated herpes virus G protein-coupled receptor during cellular
      transformation.
AB  - Kaposi's sarcoma-associated herpes virus (KSHV) contributes to the pathogenesis
      of Kaposi's sarcoma and primary effusion lymphomas. KSHV encodes a G protein
      coupled receptor (KSHV-GPCR) that signals constitutively and transforms NIH3T3
      cells. Here, we show that KSHV-GPCR transformation requires activation of the
      small G protein Rac1 and its effector, the p21-activated kinase 1 (Pak1). Either
      transient or sustained expression of KSHV-GPCR activated both Rac1 and Pak1.
      Furthermore, expression of dominant-negative mutants of Rac (RacN17) or Pak1
      (PakR299, Pak-PID) inhibited KSHV-GPCR-induced focus formation and growth in soft
      agar. We also demonstrate that signaling from Pak1 to nuclear factor-kappaB
      (NFkappaB) is required for cell transformation induced by KSHV-GPCR. KSHV-GPCR
      induced transcriptional activation by NFkappaB. This process is inhibited by the
      PAK-PID, whereas reciprocally, expression of constitutively active Pak1
      (PakL107F) activated NFkappaB comparably to KSHV-GPCR. The Pak-PID and RacN17
      inhibited the KSHV-GPCR-induced phosphorylation of inhibitor of kappaB kinase
      beta and inhibitor of kappaB-alpha, implying that it is Pak1-dependent
      phosphorylation and subsequent destruction of the inhibitor of kappaB proteins
      that allows NFkappaB activation. Finally, experiments with the KSHV-GPCR inverse
      agonist interferon-gamma-inducible protein-10, the Galpha(i) inhibitor pertussis
      toxin, and an inhibitor of phosphatidylinositol 3'-kinase, wortmannin, indicate
      that signaling through the Galpha(i) pathway and phosphatidylinositol 3'-kinase
      contributes to the cell transformation and NFkappaB activation induced by the
      KSHV-GPCR.

PMID- 14695201
TI  - Keratinocyte growth factor produced by gastric fibroblasts specifically
      stimulates proliferation of cancer cells from scirrhous gastric carcinoma.
AB  - It has been previously reported (M. Yashiro et al., Jpn. J. Cancer Res., 84: 883
      886, 1994) that a growth factor secreted by human gastric fibroblasts stimulated
      proliferation of human scirrhous gastric carcinoma cells in vitro, suggesting a
      similar paracrine action in the gastric submucosa. The present study established
      the identity of the growth factor as keratinocyte growth factor (KGF). Increase
      in numbers and incorporation of [(3)H]thymidine in scirrhous gastric carcinoma
      cell lines (OCUM-2M and OCUM-11) in response to culture medium from a gastric
      fibroblast line (NF-8 and NF-21) were duplicated by substitution of KGF and
      inhibited by addition of anti-KGF antibody. Effects were specific for scirrhous
      carcinoma cells in distinction to well-differentiated gastric carcinoma cell
      lines. Fibroblasts, especially gastric fibroblasts, expressed KGF mRNA, whereas
      gastric cancer cells did not. Conversely, scirrhous gastric cancer cells
      expressed more KGF receptor mRNA than well-differentiated gastric adenocarcinoma
      cell, whereas gastric fibroblasts did not express this mRNA. ELISA detected high
      concentrations of KGF in medium from gastric fibroblasts, much lower
      concentration in medium from other fibroblasts, and no KGF in medium from gastric
      cancer cells. Western analysis indicated that KGF in gastric fibroblasts lysates
      had a molecular weight of M(r) 19,000, within the range suggested in our previous
      report. Thus, gastric fibroblasts secretion of KGF is likely to underline the
      remarkable proliferation of scirrhous gastric cancer cells in a paracrine manner.

PMID- 14695203
TI  - Patterns of chromosomal imbalances defines subgroups of breast cancer with
      distinct clinical features and prognosis. A study of 305 tumors by comparative
      genomic hybridization.
AB  - Chromosomal copy number aberrations (CNAs) are common in breast cancer and
      involve genomic regions in a frequency and combination, suggesting distinct
      routes of tumor development. We studied chromosomal gains (+) and losses (-) by
      comparative genomic hybridization from a series of 305 unselected primary
      invasive breast cancers. CNAs were observed in >90% of the tumors and involved
      all chromosomal arms in various frequencies, the most common being +1q (55%), +8q
      (41%), +16p (40%), +17q (28%), -13q (27%), -16q (22%), +20q (19%), -8p (18%), and
      +11q (16%). Eighteen pairs of CNAs were revealed as significantly associated
      using Fisher's exact test with Bonferroni correction, the most common pairs being
      -8p/+8q, +17q/+20q, and -4q/-13q. To study more complex relationships between
      individual CNAs, principal component analysis and distance-based tree modeling
      were performed independently. Three distinct patterns of CNAs were observed.
      Group A was defined by +1q, +16p, and -16q, group B by +11q, +20q, +17q, and 
      13q, and group C by -8p and +8q. Group A was correlated to positive estrogen
      receptor and progesterone receptor (PgR) status (P < 0.001 and P < 0.05,
      respectively). Groups B and C were correlated to DNA nondiploidy (P < 0.001 and P
      < 0.05), high histological grade and lymph node positivity (P < 0.05), and group
      B also to high proliferation rate, large primary tumor size (P < 0.001), and
      negative PgR status (P < 0.05). Patients with aberrations in group A only had a
      significantly higher breast cancer survival rate than all other patients. The
      worst survival was seen for patients with aberrations in group C only along with
      the patients displaying aberrations from all CNA pattern groups (ABC). The 5-year
      survival rates vary from 96% in group A to 56% in group C. These correlations
      were independent of node status, tumor size, and PgR status in a multivariate
      analysis. We conclude that patterns of copy number gains and losses define breast
      tumors with distinct clinicopathological features and patient prognosis.

PMID- 14695202
TI  - MKP-1-induced dephosphorylation of extracellular signal-regulated kinase is
      essential for triggering nitric oxide-induced apoptosis in human breast cancer
      cell lines: implications in breast cancer.
AB  - Apoptosis is regulated by a series of biochemical events that commits a cell to
      death. We are interested in understanding and have been investigating the
      mechanisms by which nitric oxide (NO) induces apoptosis in human breast cancer
      cell lines. In this study, we investigated the possible interplay of
      extracellular signal-regulated kinase (ERK) and Akt pathways in NO-induced
      apoptosis. MKP-1 transcripts were induced in these cells as early as 4 h, peaking
      at 8 h leading to inactivation of ERK1/2 at 16-24 h after exposure to NO. We also
      found 50% decrease in the levels pAkt at 24 h of DETA-NONOate treatment. The
      inactivation of ERK1/2 preceded the dephosphorylation of Akt and apoptosis. NO
      was not able to inactivate ERK1/2 or Akt or to induce apoptosis in the presence
      of a phosphatase inhibitor, sodium orthovanadate, or antisense oligonucleotides,
      suggesting a cross-talk between the two pathways. NO also up-regulated MKP-1 in
      another breast cancer cell line, ZR 75-30, which led to inactivation of ERK1/2
      and induced apoptosis. In MDA-MB-231, NO did not induce MKP-1, and there was no
      ERK inactivation or apoptosis. Our results indicate that expression of MKP-1 by
      NO leading to dephosphorylation of ERK1/2 is the initial essential event that
      commits the cells to the apoptotic pathway in breast cancer cells.

PMID- 14695205
TI  - Cellular and genetic characterization of human adult bone marrow-derived neural
      stem-like cells: a potential antiglioma cellular vector.
AB  - We describe the in vitro isolation and expansion of cells capable of forming
      neurosphere-like aggregates from human adult bone marrow. Cells within these
      passaged spheroids can differentiate into astrocytes, specific neuronal subtypes,
      and oligodendrocytes and have gene expression profiles similar to human fetal
      brain-derived neural stem cells. Genetically modified neural-competent bone
      marrow-derived cells efficiently migrate toward distant sites of brain injury and
      tumor in vivo, where they differentiate and express therapeutic transgenes when
      transplanted into the brains of mice. These studies suggest that adult bone
      marrow may serve as a large reservoir for autologous neural stem-like cells for
      future therapeutic strategies.

PMID- 14695204
TI  - Cephalostatin 1 selectively triggers the release of Smac/DIABLO and subsequent
      apoptosis that is characterized by an increased density of the mitochondrial
      matrix.
AB  - Cephalostatin 1 is a bis-steroidal marine natural product with a unique
      cytotoxicity profile in the in vitro screen system of the National Cancer
      Institute, suggesting that it may affect novel molecular target(s). Here we show
      that cephalostatin 1 induces a novel pathway of receptor-independent apoptosis
      that selectively uses Smac/DIABLO (second mitochondria-derived activator of
      caspases/direct inhibitor of apoptosis-binding protein with a low isoelectric
      point) as a mitochondrial signaling molecule. At nanomolar concentrations,
      cephalostatin 1 triggers dose- and time-dependent DNA fragmentation in leukemia
      Jurkat T cells. Apoptosis was found to be dependent on caspase activity because
      the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone
      blocks cephalostatin 1-mediated DNA fragmentation. The CD95 death receptor as
      well as other caspase-8-requiring death receptors were not involved because
      Jurkat T cells lacking the CD95 receptor or caspase-8 and control cells responded
      equally to cephalostatin 1. Although cephalostatin 1 affects mitochondria by
      dissipating the mitochondrial membrane potential, neither cytochrome c nor
      apoptosis-inducing factor is released, as shown by Western blot analysis.
      Interestingly, cephalostatin 1 selectively triggers the mitochondrial release of
      the inhibitor of apoptosis antagonist Smac/DIABLO. Overexpression of the
      antiapoptotic protein Bcl-x(L) delayed both Smac/DIABLO release and onset of
      apoptosis, suggesting that Smac/DIABLO is required for cephalostatin 1-induced
      apoptosis. This new mitochondrial pathway is accompanied by marked structural
      changes of mitochondria as shown by transmission electron microscopy.

PMID- 14695206
TI  - Combined therapy with direct and indirect angiogenesis inhibition results in
      enhanced antiangiogenic and antitumor effects.
AB  - The multifaceted nature of the angiogenic process in malignant neoplasms suggests
      that protocols that combine antiangiogenic agents may be more effective than
      single-agent therapies. However it is unclear which combination of agents would
      be most efficacious and will have the highest degree of synergistic activity
      while maintaining low overall toxicity. Here we investigate the concept of
      combining a "direct" angiogenesis inhibitor (endostatin) with an "indirect"
      antiangiogenic compound [SU5416, a vascular endothelial growth factor receptor 2
      (VEGFR2) receptor tyrosine kinase (RTK) inhibitor]. These angiogenic agents were
      more effective in combination than when used alone in vitro (endothelial cell
      proliferation, survival, migration/invasion, and tube formation tests) and in
      vivo. The combination of SU5416 and low-dose endostatin further reduced tumor
      growth versus monotherapy in human prostate (PC3), lung (A459), and glioma (U87)
      xenograft models, and reduced functional microvessel density, tumor
      microcirculation, and blood perfusion as detected by intravital microscopy and
      contrast-enhanced Doppler ultrasound. One plausible explanation for the
      efficacious combination could be that, whereas SU5416 specifically inhibits
      vascular endothelial growth factor signaling, low-dose endostatin is able to
      inhibit a broader spectrum of diverse angiogenic pathways directly in the
      endothelium. The direct antiangiogenic agent might be able to suppress
      alternative angiogenic pathways up-regulated by the tumor in response to the
      indirect, specific pathway inhibition. For future clinical evaluation of the
      concept, a variety of agents with similar mechanistic properties could be tested.

PMID- 14695207
TI  - Adenosine 5'-triphosphate-sensitive potassium channel-mediated blood-brain tumor
      barrier permeability increase in a rat brain tumor model.
AB  - Brain tumor microvessels/capillaries limit drug delivery to tumors by forming a
      blood-brain tumor barrier (BTB). The BTB overexpresses ATP-sensitive potassium
      (K(ATP)) channels that are barely detectable in normal brain capillaries, and
      which were targeted for BTB permeability modulation. In a rat brain tumor model,
      we infused minoxidil sulfate (MS), a selective K(ATP) channel activator, to
      obtain sustained, enhanced, and selective drug delivery, including various sized
      molecules, across the BTB to brain tumors. Glibenclamide, a selective K(ATP)
      channel inhibitor, significantly attenuated the MS-induced BTB permeability
      increase. Immunocytochemistry and glibenclamide binding studies showed increased
      K(ATP) channel density distribution on tumor cells and tumor capillary
      endothelium, which was confirmed by K(ATP) channel potentiometric assay in tumor
      cells and brain endothelial cells cocultured with brain tumor cells. MS infusion
      in rats with brain tumors significantly increased transport vesicle density in
      tumor capillary endothelial and tumor cells. MS facilitated increased delivery of
      macromolecules, including Her-2 antibody, adenoviral-green fluorescent protein,
      and carboplatin, to brain tumors, with carboplatin significantly increasing
      survival in brain tumor-bearing rats. K(ATP) channel-mediated BTB permeability
      increase was also demonstrated in a human, brain tumor xenograft model. We
      conclude that K(ATP) channels are a potential target for biochemical modulation
      of BTB permeability to increase antineoplastic drug delivery selectively to brain
      tumors.

PMID- 14695208
TI  - A fully human monoclonal antibody to the insulin-like growth factor I receptor
      blocks ligand-dependent signaling and inhibits human tumor growth in vivo.
AB  - The insulin-like growth factor I receptor (IGF-IR) is overexpressed in many
      diverse tumor types and is a critical signaling molecule for tumor cell
      proliferation and survival. Therapeutic strategies targeting the IGF-IR may
      therefore be effective broad-spectrum anticancer agents. Through screening of a
      Fab phage display library, we have generated a fully human antibody (A12) that
      binds to the IGF-IR with high affinity (4.11 x 10(-11) M) and inhibits ligand
      binding with an IC(50) of 0.6-1 nM. Antibody-mediated blockade of ligand binding
      to the IGF-IR inhibited downstream signaling of the two major insulin-like growth
      factor (IGF) pathways, mitogen-activated protein kinase and phosphatidylinositol
      3'-kinase/Akt, in MCF7 human breast cancer cells. As a result, the mitogenic and
      proliferative potential of IGF-I and IGF-II were significantly reduced. A12 did
      not block insulin binding to the insulin receptor but could block binding to
      atypical IGF-IR in MCF7 cells. In addition, A12 was shown to induce IGF-IR
      internalization and degradation on specific binding to tumor cells, resulting in
      a significant reduction in cell surface receptor density. In xenograft tumor
      models in vivo, IGF-IR blockade by A12 was shown to occur rapidly, resulting in
      significant growth inhibition of breast, renal, and pancreatic tumors.
      Histological analysis of tumor sections demonstrated a marked increase in
      apoptotic tumor cells in antibody-treated animals. These results demonstrate that
      A12 possesses strong antitumor activity in vitro and in vivo and may therefore be
      an effective therapeutic candidate for the treatment of cancers that are
      dependent on IGF-IR signaling for growth and survival.

PMID- 14695209
TI  - Geranylgeranyltransferase I inhibitor GGTI-2154 induces breast carcinoma
      apoptosis and tumor regression in H-Ras transgenic mice.
AB  - Treatment of H-Ras transgenic mice with the geranylgeranyltransferase I (GGTase
      I) inhibitor GGTI-2154 results not only in halting the growth of aggressive
      breast tumors but actually in inducing the regression (54 +/- 3%) of all 19
      tumors analyzed. The farnesyltransferase (FTase) inhibitor FTI-2148 induced an
      average of 87 +/- 3% regression in the 13 tumors analyzed. GGTase I, but not
      FTase, is inhibited in breast tumors after treatment with GGTI-2154, whereas in
      tumors from mice treated with FTI-2148, only FTase is inhibited. The processing
      of the geranylgeranylated proteins RhoA, Rap1, and R-Ras, but not the
      farnesylated proteins H-Ras and HDJ-2, is inhibited in tumors obtained from mice
      treated with GGTI-2154. GGTI-2154 and FTI-2148 suppress constitutively activated
      phospho-Erk1/2 and phospho-Akt, induce apoptosis, and induce differentiation
      toward ductolobular breast epithelium. The data demonstrate that
      geranylgeranylated proteins are critical in H-Ras oncogenesis in vivo and give
      strong support for GGTase I as a target for anticancer drug discovery.

PMID- 14695210
TI  - Combinatorial efficacy achieved through two-point blockade within a signaling
      pathway-a chemical genetic approach.
AB  - Whether the apparent efficacy of a specific kinase inhibitor is attributable
      solely to inhibition of its primary target, or to combined inhibition of
      additional unidentified kinases, is a critical issue in cancer therapy. We used a
      chemical genetic approach to generate a selective inhibitor of v-erbB [a
      transforming allele of epidermal growth factor receptor (EGFR)] and interrogated
      inhibition in known downstream signaling pathways. On the basis of this analysis,
      we hypothesized that dual inhibition of v-erbB and phosphatidylinositol 3' (PI3)
      kinases could show improved potency. We, therefore, used two different cell lines
      to examine the effects of v-erbB or EGFR inhibitors, in combination with PI3
      kinase inhibitors, in mouse models for EGFR-driven cancers. When treated with
      NaPP1, v-erbB-as1-transformed fibroblasts showed cell-cycle arrest and decreased
      activity of Akt kinase. Inhibitors of v-erbB-as1 and of PI3 kinase showed
      enhanced efficacy in treating established 3T3:v-erbB-as1 tumor allografts. We
      extended these results to the human glioma cell line U87:MG transduced with
      DeltaEGFR, a tumor-derived activated allele, treating tumor-bearing mice with
      vehicle, the EGFR inhibitor ZD1839, LY294002, or ZD1839 plus LY294002. In human
      glioma xenografts, inhibition of EGFR cooperated similarly with inhibition of PI3
      kinase. Our experiments provide a preclinical mechanistic basis for combining
      biologically based therapies directed against two targets within a complex
      signaling cascade.

PMID- 14695211
TI  - Identification of genes expressed in malignant cells that promote invasion.
AB  - To systematically identify genes related to invasion a three-dimensional
      multicellular matrix invasion assay was used to classify human tumor cell lines
      as stromal invasion positive or stromal invasion negative. Cells from two of the
      primary cell types of the stromal compartment [endothelial cells (HMVEC) and
      myofibroblasts (HDF)] were assayed for invasion into tumor cell clusters (breast
      carcinoma, ovarian carcinoma, prostate carcinoma, lung carcinoma, and melanoma).
      Four tumor cell lines (MDA-MB231, SKOV-3, A375, and MEL624) scored invasion
      positive, and four tumor cell lines (LNCaP, DU145, PC3, and A549) scored invasion
      negative. Serial analysis of gene expression (SAGE) libraries generated from the
      tumor cell lines were analyzed by GeneSpring Hierarchical clustering, t test, and
      chi(2) test. Clusters emerged that reflected the behavior in the cell culture
      assay. Of the 47 most highly differentially expressed genes, 30 were selected for
      confirmation by real-time PCR, and 9 had good correlation with normalized serial
      analysis of gene expression tag counts. The strongest correlations were for bone
      marrow stromal antigen 2, stathmin-like 3, tumor necrosis factor receptor
      superfamily member 5, and hepatocyte growth factor tyrosine kinase substrate. In
      situ hybridization of metastatic and nonmetastatic ovarian cancer demonstrated
      selective expression of bone marrow stromal antigen 2 and tumor necrosis factor
      receptor superfamily member 5 in the metastatic disease. This combination
      approach appears to be a powerful tool for identifying genes that may be useful
      as diagnostic markers and/or as therapeutic targets for invasive solid tumors.

PMID- 14695212
TI  - Induction of PIG3 and NOXA through acetylation of p53 at 320 and 373 lysine
      residues as a mechanism for apoptotic cell death by histone deacetylase
      inhibitors.
AB  - Two controversial issues regarding p53 are whether it is involved in apoptosis
      induction of tumor cells by a histone deacetylase (HDAC) inhibitor and, given
      that p53 is indeed involved, which genes of acetylated p53 targets are
      responsible for giving rise to apoptotic death. We, in the present study, first
      confirmed that some substantial extent of apoptotic cell death was seen when p53
      deficient cells (KATO-III) were transfected with wild-type p53 and treated with
      sodium butyrate (SB) or trichostatin A. By Western blotting, using specific
      antibodies, we then demonstrated that residues 320, 373, and 382 lysines of p53
      were acetylated in KATO-III cells transfected with wild-type p53 (KATO-III/p53)
      treated with a HDAC inhibitor. However, as revealed by terminal deoxynucleotidyl
      transferase-mediated nick end labeling staining, only those KATO-III cells
      transfected with K320R p53 or K373R p53 became insensitive to the HDAC inhibitor,
      suggesting that these two residues of p53 may be essential for HDAC inhibitor
      induced apoptosis, whereas others such as K382R p53 may not. Furthermore, reverse
      transcription-PCR demonstrated that among various p53-related proapoptotic genes,
      expression of PIG3 and NOXA were clearly enhanced by SB treatment in KATO-III/p53
      cells but not in KATO-III/K320R or KATO-III/K373R cells. Finally, we revealed
      that apoptosis could be evoked by SB even in cells where p53 mutations occur at
      residues other than 320 lysine or 373 lysine (TMK-1 and HSC-39 cells) and that
      this apoptosis was significantly, although not totally, suppressed by the anti
      p53 antisense. It was, therefore, concluded that acetylation of the p53 molecule
      at residues 320 and 373, giving rise to up-regulation of PIG3 and NOXA, is one of
      the mechanisms for induction of apoptosis by HDAC inhibitors in cancer cells.

PMID- 14695213
TI  - Butyrates, as a single drug, induce histone acetylation and granulocytic
      maturation: possible selectivity on core binding factor-acute myeloid leukemia
      blasts.
AB  - Acute myeloid leukemia (AML) is a disease characterized by a block of maturation.
      Genes coding for core binding factors are rearranged in a considerable subset of
      AML cases and result in an altered interaction of core binding factor (CBF)
      subunits with transcriptional coregulators (NCoR/SMRT). Recruitment of histone
      deacetylase is also altered in AML, and a subsequent transcriptional repression
      of target genes involved in myeloid maturation is determined. We determined here
      the effects of two histone deacetylase inhibitors, sodium butyrate and the stable
      prodrug xylitol butyrate derivative (D1), on a t(8;21)-positive cell line (Kasumi
      1) as well as primary AML blasts. Exposure (24-96 h) to butyrates (1 mM) of
      Kasumi-1 cells induced histone H4 acetylation, whereas H3 acetylation was
      unchanged. Induction of morphological and immunophenotypic granulocytic
      maturation (96 h), also confirmed by an increased expression of CAAT/enhancer
      binding protein alpha, was observed. Inhibition of proliferation and apoptosis
      via activation of caspase-9 was also observed. In primary AML blasts, butyrates
      (0.5 mM) increased histone H4 acetylation of 18 of 19 cases tested. Terminal
      granulocytic maturation was observed in all cases (5 of 5) characterized by
      chromosomal translocations involving CBF, whereas in non-CBF cases, maturation
      was incomplete (4 of 8) or absent (4 of 8). Our data indicate the possibility to
      effectively remove, in CBF AML cases, the maturation block generated by histone
      deacetylase stable recruitment, contributing to a possible development of
      molecularly targeted therapies of AML.

PMID- 14695214
TI  - Intratumoral immunization with tumor RNA-pulsed dendritic cells confers antitumor
      immunity in a C57BL/6 pancreatic murine tumor model.
AB  - Pancreatic tumors lack adequate recruitment of immunocompetent cells, especially
      dendritic cells (DCs). We have shown previously that coculturing of natural
      killer-like T cells with DCs transfected with pancreatic tumor cell line-derived
      RNA reverses pancreatic carcinoma cell resistance by directly triggering natural
      killer-like T lymphocytes in vitro. In the present study, we tested triggering of
      specific T lymphocytes in vivo by using an immunocompetent mouse strain
      (C57BL/6). Syngenic, bone marrow-derived DCs were pulsed with tumor RNA derived
      from the pancreatic cell line PANC02. This cell line is a ductal pancreatic
      adenocarcinoma and shows high resistance to every known class of clinically
      active antitumor agent. PANC02 cells were implanted orthotopically via ultrasound
      guidance and led to pancreatic tumor formation in all of the mice. Thereafter,
      tumor RNA-pulsed DCs were injected intratumorally. Intratumoral administration of
      tumor RNA-pulsed DCs induced significantly more potent protective immunity than
      s.c. or i.v. administration. It was significantly more effective than
      administration with unpulsed DCs or DCs pulsed with a control tumor RNA derived
      from a lymphomatous cell line (EL4). The antitumor effect was caused by induction
      of antigen-specific T lymphocytes as shown by additional in vitro studies. These
      results favor intratumoral injection of tumor RNA-pulsed DCs for immunotherapy of
      pancreatic cancer.

PMID- 14695215
TI  - Repression of vascular endothelial growth factor A in glioblastoma cells using
      engineered zinc finger transcription factors.
AB  - Angiogenic factors are necessary for tumor proliferation and thus are attractive
      therapeutic targets. In this study, we have used engineered zinc finger protein
      (ZFP) transcription factors (TFs) to repress expression of vascular endothelial
      growth factor (VEGF)-A in human cancer cell lines. We create potent
      transcriptional repressors by fusing a designed ZFP targeted to the VEGF-A
      promoter with either the ligand-binding domain of thyroid hormone receptor alpha
      or its viral relative, vErbA. Moreover, this ZFP-vErbA repressor binds its
      intended target site in vivo and mediates the specific deacetylation of histones
      H3 and H4 at the targeted promoter, a result that emulates the natural repression
      mechanism of these domains. The potential therapeutic relevance of ZFP-mediated
      VEGF-A repression was addressed using the highly tumorigenic glioblastoma cell
      line U87MG. Despite the aberrant overexpression of VEGF-A in this cell line,
      engineered ZFP TFs were able to repress the expression of VEGF-A by >20-fold. The
      VEGF-A levels observed after ZFP TF-mediated repression were comparable to those
      of a nonangiogenic cancer line (U251MG), suggesting that the degree of repression
      obtained with the ZFP TF would be sufficient to suppress tumor angiogenesis.
      Thus, engineered ZFP TFs are shown to be potent regulators of gene expression
      with therapeutic promise in the treatment of disease.

PMID- 14695216
TI  - Novel cisplatin-incorporated polymeric micelles can eradicate solid tumors in
      mice.
AB  - Polymeric micelles incorporating cisplatin (CDDP) were prepared through the
      polymer-metal complex formation between CDDP and poly(ethylene glycol)
      poly(glutamic acid) block copolymers, and their utility as a tumor-targeted drug
      delivery system was investigated. CDDP-incorporated micelles (CDDP/m) had a size
      of 28 nm with remarkably narrow distribution. CDDP/m were very stable in
      distilled water even in long-time storage, but exhibited a sustained drug release
      accompanied with the decay of the carrier itself in physiological saline. These
      micelles showed remarkably prolonged blood circulation and effectively
      accumulated in solid tumors (Lewis lung carcinoma cells) according to the passive
      targeting manner (20-fold higher than free CDDP). Reduced accumulation of the
      micelles in normal organs provided high selectivity to the tumor. In vivo
      antitumor activity assay demonstrated that both free CDDP and the CDDP/m had
      significant antitumor activity in C 26-bearing mice compared with nontreatment (P
      < 0.05 for free CDDP; P < 0.01 for CDDP/m), but complete tumor regression was
      observed only for the treatment with CDDP/m. Four of 10 mice treated with CDDP/m
      (4 mg/kg; five times administration at 2-day intervals) showed complete tumor
      regression with no significant body weight loss, whereas free CDDP treatment at
      the same drug dose and regime resulted in tumor survivals and approximately 20%
      of body weight loss. These data suggest that CDDP/m could be a promising
      formulation of CDDP for the targeted therapy of solid tumors.

PMID- 14695217
TI  - Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro
      and in vivo radiation response of cervical tumor cells via the heat shock protein
      90-mediated intracellular signaling and cytotoxicity.
AB  - Ansamycin antibiotics inhibit function of the heat shock protein (HSP) 90,
      causing selective degradation of several intracellular proteins regulating such
      processes as proliferation, cell cycle regulation, and prosurvival signaling
      cascades. HSP90 has been identified previously as a molecular target for
      anticancer agents, including ionizing radiation (IR). Therefore, we hypothesized
      that the ansamycin geldanamycin and its 17-allylamino-17-demethoxy analog (17
      AAG), which inhibit HSP90, would enhance tumor cell susceptibility to the
      cytotoxicity of IR. Treatment of two human cervical carcinoma cell lines (HeLa
      and SiHa) with geldanamycin and 17-AAG resulted in cytotoxicity and, when
      combined with IR, enhanced the radiation response, each effect with a temporal
      range from 6 to 48 h after drug exposure. In addition, mouse in vivo models using
      17-AAG at clinically achievable concentrations yielded results that paralleled
      the in vitro radiosensitization studies of both single and fractioned courses of
      irradiation. The increase in IR-induced cell death appears to be attributable to
      a combination of both programmed and nonprogrammed cell death. We also measured
      total levels of several prosurvival and apoptotic signaling proteins. Akt1,
      extracellular signal-regulated kinase-1, Glut-1, HER-2/neu, Lyn, cAMP-dependent
      protein kinase, Raf-1, and vascular endothelial growth factor expression were
      down-regulated in 17-AAG-treated cells, identifying these factors as molecular
      markers and potential therapeutic targets. Finally, a series of immortalized and
      human papillomavirus-transformed cell lines were used to demonstrate that the
      radiosensitizing effects of 17-AAG were limited to transformed cells, suggesting
      a possible differential cytotoxic effect. This work shows that altered HSP90
      function induces significant tumor cytotoxicity and radiosensitization,
      suggesting a potential therapeutic utility.

PMID- 14695218
TI  - MICA/NKG2D-mediated immunogene therapy of experimental gliomas.
AB  - The failure of conventional cancer therapy renders glioblastoma an attractive
      target for immunotherapy. Tumor cells expressing ligands of the activating
      immunoreceptor NKG2D stimulate tumor immunity mediated by natural killer (NK),
      gammadelta T, and CD8(+) T cells. We report that human glioma cells express the
      NKG2D ligands MICA, MICB, and members of the UL16-binding protein family
      constitutively. However, glioma cells resist NK cell cytolysis because of high
      MHC class I antigen expression. Plasmid-mediated or adenovirus-mediated
      overexpression of MICA in glioma cells enhances their sensitivity to NK and T
      cell responses in vitro and markedly delays the growth of s.c. and intracerebral
      LN-229 human glioma cell xenografts in nude mice and of SMA-560 gliomas in
      syngeneic VMDk mice. Glioma cells forming progressive tumors after implantation
      of stably MICA-transfected human LN-229 cells lost MICA expression, indicating a
      strong selection against MICA expression in vivo. Rejection of MICA-expressing
      SMA-560 cells in VMDk mice resulted in protective immunity to a subsequent
      challenge with wild-type tumor cells. Finally, the growth of syngeneic
      intracerebral SMA-560 tumors is inhibited by peripheral vaccination with
      adenovirus-mediated, MICA-infected irradiated tumor cells, and vaccination
      results in immune cell activation in the NK and T-cell compartments in vivo.
      These data commend MICA immunogene therapy as a novel experimental treatment for
      human malignant gliomas.

PMID- 14695219
TI  - Extra-lymphatic solid tumor growth is not immunologically ignored and results in
      early induction of antigen-specific T-cell anergy: dominant role of cross
      tolerance to tumor antigens.
AB  - A better understanding of how solid malignancies arise in an immunocompetent
      host, avoid immune recognition, and ultimately progress to widely disseminated
      cancer is essential to effectively harness the immune system against solid
      tumors. Because of their extra-lymphatic localization, it has been proposed that
      solid malignancies are just ignored by the immune system, thereby allowing their
      uncontrolled growth and dissemination. Alternatively, as most of the solid tumors
      are unable to express costimulatory molecules, the "signal one without signal
      two" model of tolerance induction has been frequently evoked to account for the
      failure of the immune system to reject antigenic tumors in vivo. In this study,
      we showed, however, that the extra-lymphatic growth of solid tumors is not
      immunologically ignored by the lymphoid compartment, resulting instead in the
      early induction of antigen-specific CD4(+) T-cell tolerance. Furthermore,
      analysis of parent-into-F1 bone marrow (BM) chimeras demonstrates that
      presentation of tumor antigens by BM-derived antigen-presenting cells represents
      the dominant mechanism in solid tumor-induced CD4(+) T-cell tolerance. Our
      findings of early development of antigen-specific T-cell unresponsiveness
      mediated by BM-derived antigen-presenting cells, not only provides a plausible
      explanation for the failure of the immune system to reject antigenic solid tumors
      in vivo, but more importantly, they have identified a barrier that, if
      appropriately manipulated, may lead to approaches to effectively harness the
      immune system against solid malignancies.

PMID- 14695220
TI  - In vivo antitumor activity of interleukin 21 mediated by natural killer cells.
AB  - Immunotherapy with high-dose interleukin (IL) 2 has been shown to successfully
      treat tumors in animal models and cause dramatic tumor regressions in some
      patients with metastatic melanoma, renal cell carcinoma, and non-Hodgkin's
      lymphoma. However, toxicity associated with IL-2 administration has compromised
      its widespread use in the clinic. IL-21 is a more recently discovered cytokine
      produced by activated CD4(+) T cells that shares significant sequence homology to
      IL-2, IL-4, and IL-15. Because IL-21 and IL-2 and their receptors share
      significant sequence similarities and both cytokines can stimulate T and natural
      killer (NK) cells, we sought to study whether IL-21, like IL-2, exhibits
      antitumor effects in vivo. In this study, we treated established s.c. tumor in
      mice by systemically administering plasmid DNA encoding murine IL-21 using a
      hydrodynamics-based gene delivery technique. Administration of IL-21 plasmid DNA
      resulted in high levels of circulating IL-21 in vivo. Treatment of tumor-bearing
      mice with IL-21 plasmid DNA significantly inhibited the growth of B16 melanoma
      and MCA205 fibrosarcoma in a dose-dependent manner without significant toxicity
      and increased the survival rate, compared with mice treated with control plasmid
      DNA. In vivo depletion of either CD4(+) or CD8(+) T cells did not affect IL-21
      mediated antitumor activity. However, depletion of NK cells completely abolished
      IL-21-induced tumor inhibition. Consistent with this, the antitumor activity of
      IL-21 seemed to be mediated through enhanced cytolytic activity of NK cells. Our
      study suggests that IL-21 has significant antitumor activity and may have
      therapeutic potentials as an antitumor agent in the clinic.

PMID- 14695221
TI  - Beta-glucan functions as an adjuvant for monoclonal antibody immunotherapy by
      recruiting tumoricidal granulocytes as killer cells.
AB  - The tumor-killing mechanisms available to monoclonal antibodies (mAbs; e.g.,
      antagonism of growth factor receptors, antibody-dependent cell-mediated
      cytotoxicity) limit efficacy. Previous studies suggested that i.v. beta-glucan
      might function as an adjuvant for antitumor mAbs. beta- Glucan had been shown to
      function via the iC3b-receptor complement receptor 3 (CR3; CD11b/CD18) thereby
      enhancing leukocyte killing of tumor cells coated with iC3b via naturally
      occurring antitumor antibodies. Therapy with beta-glucans was limited by levels
      of natural antibodies and by tumor escape through elimination of antigen-positive
      cells. Accordingly, it was hypothesized that beta-glucan responses could be
      improved by combined administration with antitumor mAbs. Five tumor models were
      explored in BALB/c or C57Bl/6 mice using tumors that expressed either high levels
      of naturally occurring antigens (e.g., G(D2) ganglioside) or recombinant human
      MUC1. In comparison with antitumor mAb or beta-glucan alone, combined treatment
      with mAb plus beta-glucan produced significantly greater tumor regression in all
      models that included mammary, s.c., and hepatic tumors. Tumor-free survival only
      occurred in models that incorporated stable expression of the target antigen.
      beta-Glucan enhancement of the mAb tumoricidal response did not occur in mice
      deficient in either leukocyte CR3 (CD11b(-/-)) or serum C3, confirming the
      requirement for CR3 on leukocytes and iC3b on tumors. Granulocytes appeared to be
      primarily responsible for tumoricidal activity, because beta-glucan therapeutic
      responses did not occur in granulocyte-depleted mice. These data suggest that the
      therapeutic efficacy of mAbs known to activate complement (e.g., Herceptin,
      Rituxan, and Erbitux) could be significantly enhanced if they were combined with
      beta-glucan.

PMID- 14695222
TI  - Human kallikrein 14: a new potential biomarker for ovarian and breast cancer.
AB  - Human kallikrein gene 14 (KLK14) is a recently discovered member of the tissue
      kallikrein family of secreted serine proteases, which includes hK3/prostate
      specific antigen, the best cancer biomarker to date. Given that KLK14 is
      hormonally regulated, differentially expressed in endocrine-related cancers, and
      a prognostic marker for breast and ovarian cancer at the mRNA level, we
      hypothesize that its encoded protein, hK14, like hK3/prostate-specific antigen,
      may constitute a new biomarker for endocrine-related malignancies. The objective
      of this study was to generate immunological reagents for hK14, to develop an
      ELISA and immunohistochemical techniques to study its expression in normal and
      cancerous tissues and biological fluids. Recombinant hK14 was produced in Pichia
      pastoris, purified by affinity chromatography, and injected into mice and rabbits
      for polyclonal antibody generation. Using the mouse and rabbit antisera, a
      sandwich-type immunofluorometric ELISA and immunohistochemical methodologies were
      developed for hK14. The ELISA was sensitive (detection limit of 0.1 micro
      g/liter), specific for hK14, linear from 0 to 20 micro g/liter with between-run
      and within-run coefficients of variation of <10%. hK14 was quantified in human
      tissue extracts and biological fluids. Highest levels were observed in the
      breast, skin, prostate, seminal plasma, and amniotic fluid, with almost
      undetectable levels in normal serum. hK14 concentration was higher in 40% of
      ovarian cancer tissues compared with normal ovarian tissues. Serum hK14 levels
      were elevated in a proportion of patients with ovarian (65%) and breast (40%)
      cancers. Immunohistochemical analyses indicated strong cytoplasmic staining of
      hK14 by the epithelial cells of normal and malignant skin, ovary, breast, and
      testis. In conclusion, we report the first ELISA and immunohistochemical assays
      for hK14 and describe its distribution in tissues and biological fluids. Our
      preliminary data indicate that hK14 is a potential biomarker for breast and
      ovarian cancers.

PMID- 14695223
TI  - Identification of prognostic markers in bone sarcomas using proton-decoupled
      phosphorus magnetic resonance spectroscopy.
AB  - It has been hypothesized that the (31)Phosphorus ((31)P) nuclear magnetic
      resonance spectrum from certain tumors may provide prognostic information. The
      goal of the present study was to identify prognostic metabolic markers by using
      proton-decoupled phosphorus magnetic resonance spectroscopic imaging ((31)P
      MRSI). Twenty patients with bone [osteogenic (OS) and Ewing's (ES) and/or
      primitive neuroectodermal tumor (PNET)] sarcoma, treated with chemotherapy and
      surgery or with chemotherapy alone, underwent (31)P MRSI studies pre- and post
      therapy. The studies were performed on a 1.5 Tesla General Electric (GE) clinical
      scanner equipped with a stand-alone proton decoupler and a dual (1)H/(31)P
      surface coil pair. The limited sensitivity of the (31)P nucleus required that a
      large soft tissue component of the disease be located within 10 cm (maximum
      distance) of the body surface and the use of a highly sensitive coil placed near
      the skin surface. Proton decoupling and nuclear Overhauser enhancement were used
      to improve the spectral resolution and signal:noise ratio. Baseline (31)P
      spectral features and metabolic changes with treatment were compared with
      treatment outcome. The patients were categorized depending on survival as event
      free survivors or those who died. The pretreatment nucleoside
      triphosphate:inorganic phosphate (NTP:P(i)) ratio, an index of tumor bioenergetic
      status, was significant (P = 0.003) in differentiating event-free survivors
      versus those who died. The pretreatment NTP:P(i) was higher in patients who were
      destined to undergo a durable event-free survival compared with those who died.
      The results are promising, although a prospective study is necessary for
      confirmation. (31)P MRSI appears to be a useful tool for the prediction of
      survival before therapy in bone sarcomas.

PMID- 14695224
TI  - Dysregulated expression of COOH-terminally truncated Stat5 and loss of IL2
      inducible Stat5-dependent gene expression in Sezary Syndrome.
AB  - Sezary Syndrome (SzS) is a leukemic variant of cutaneous T-cell lymphoma
      characterized by the accumulation of clonal neoplastic CD4+ T cells. The signal
      transducers and activators of transcription (STAT) family members, Stat5a and
      Stat5b, play an important role in regulating T-cell activation. Recent studies
      have shown that inappropriate activation of STATs occurs frequently in a wide
      variety of human cancers. Here we examine the functional status of Stat5 proteins
      in SzS as compared with healthy donors. Western blotting demonstrates that in
      cytoplasmic extracts of unstimulated T cells from healthy controls two isoforms
      of Stat5, full-length and a COOH-terminal truncated isoform, termed Stat5(t), are
      present. However, bandshift assays demonstrate that only Stat5(t) translocates to
      the nucleus and binds DNA on IL-2 stimulation. In contrast, preactivated T cells
      express only full-length Stat5, which is functionally activated on IL-2
      stimulation. Analysis of Stat5 protein isoforms from five of five SzS patients
      revealed predominant aberrant expression of Stat5(t) in preactivated peripheral
      blood mononuclear cell. Furthermore, patients showed preferential IL-2-induced
      DNA binding of Stat5(t). Consistent with the inappropriate activation of Stat5(t)
      in SzS patients, real-time PCR revealed that IL-2-induced mRNA expression of the
      Stat5 target genes, Bcl-2, PIM-1, and CISH were markedly reduced. These data
      indicate that functional Stat5 isoform expression is regulated by T-cell
      activation status and that dysregulated expression of Stat5(t) in malignant T
      cells in SzS can suppress Stat5-dependent gene expression. Thus, aberrant
      expression of Stat5(t) may be one mechanism that contributes to the cellular
      transformation of T cells in this disease.

PMID- 14695225
TI  - Correspondence re: S. A. W. Fuqua et al., Estrogen receptor beta protein in human
      breast cancer: correlation with clinical tumor parameters. Cancer Res.,63: 2434
      2439, 2003.

PMID- 14695227
TI  - Erythropoietin gene therapy leads to autoimmune anemia in macaques.
AB  - Gene therapy is being considered for the delivery of therapeutic proteins. We
      evaluated the delivery of the hormone erythropoietin (EPO) into cynomolgus
      macaques through intramuscularly administered adeno-associated virus (AAV)
      vectors. As expected, the animals developed supraphysiologic levels of EPO and
      polycythemia. However, severe anemia ensued in some animals because of an
      autoimmune response to endogenous and transgene derived EPO. This is the first
      example of gene therapy leading to inadvertent auto-immunity in primates.

PMID- 14695232
TI  - The pattern and distribution of immunoglobulin VH gene mutations in chronic
      lymphocytic leukemia B cells are consistent with the canonical somatic
      hypermutation process.
AB  - The overexpanded clone in most B-cell-type chronic lymphocytic leukemia (BCLL)
      patients expresses an immunoglobulin (Ig) heavy chain variable (V(H)) region gene
      with some level of mutation. While it is presumed that these mutations were
      introduced in the progenitor cell of the leukemic clone by the canonical somatic
      hypermutation (SHM) process, direct evidence of such is lacking. Nucleotide
      sequences of the Ig V(H) genes from 172 B-CLL patients were analyzed. Previously
      described V(H) gene usage biases were noted. As with canonical SHM, mutations
      found in B-CLL were more frequent in RGYW hot spots (mutations in an RGYW motif =
      44.1%; germ line frequency of RGYW motifs = 25.6%) and favored transitions over
      transversions (transition-transversion ratio = 1.29). Significantly, transition
      preference was also noted when only mutations in the wobble position of
      degenerate codons were considered. Wobble positions are inherently unselected
      since regardless of change an identical amino acid is encoded; therefore, they
      represent a window into the nucleotide bias of the mutational mechanism. B-CLL
      V(H) mutations concentrated in complementarity-determining region 1 (CDR1) and
      CDR2, which exhibited higher replacement-to-silent ratios (CDR R/S, 4.60;
      framework region [FR] R/S, 1.72). These results are consistent with the notion
      that V(H) mutations in B-CLL cells result from canonical SHM and select for
      altered, structurally sound antigen receptors.

PMID- 14695235
TI  - A cell-surface molecule selectively expressed on murine natural interferon
      producing cells that blocks secretion of interferon-alpha.
AB  - Natural interferon (IFN)-producing cells (IPCs) recognize certain viruses and DNA
      containing deoxycytidylate-phosphatedeoxyguanylate (CpG) motifs through the toll
      like receptor (TLR) 9, resulting in secretion of IFN-alpha, interleukin 12 (IL
      12), and proinflammatory chemokines. Human IPCs are found mainly in inflamed
      lymph nodes, where they are presumably recruited from the blood to activate both
      innate and adaptive responses to microbial infections. Demonstrating IPC
      recruitment and function in murine infection models has been difficult because
      multiple antibodies are required to distinguish IPCs from other immune cells and
      very few IPCs can be recovered from lymph nodes. Here we describe a monoclonal
      antibody (mAb) that exclusively detects murine IPCs in all lymphoid organs under
      both normal and inflammatory conditions. Using this antibody, we demonstrate that
      IPCs are normally present in the T-cell zone of lymph nodes and spleen and that
      inoculation of peripheral tissues with inflammatory stimuli triggers recruitment
      of IPC into sentinel lymph nodes, whether the stimuli are able to directly
      stimulate IPCs through TLR or not. Remarkably, we show that incubation of IPCs
      with the antibody in vitro or administration of the antibody in vivo dramatically
      reduce secretion of IFN-alpha in response to CpG DNA without causing IPC
      depletion. Thus, the antibody identifies an IPC-specific surface molecule that,
      when engaged, inhibits IFN-alpha secretion.

PMID- 14695237
TI  - Fenretinide enhances rituximab-induced cytotoxicity against B-cell lymphoma
      xenografts through a caspase-dependent mechanism.
AB  - The anti-CD20 monoclonal antibody rituximab induces remission in 40% to 60% of
      patients with indolent B-cell lymphoma, but virtually all patients have relapses.
      We evaluated the efficacy of concurrent administration of another biologic agent,
      N-(4-hydroxyphenyl) retinamide (4HPR, fenretinide) with rituximab against a
      variety of human B-cell lymphoma cell lines (Ramos, DHL-4, and FL-18) in vivo.
      Concurrent 4HPR and rituximab administration prevented tumor progression of
      lymphoma-bearing mice in a minimal disease model (rituximab + 4HPR, 100%
      progression free; rituximab alone, 37.5% progression free, P =.01; 4HPR alone,
      12.5% progression free, P <.01; controls, 0% progression free, P <.01).
      Combinations of 4HPR + rituximab exceeded the predicted 50% additive rate of
      disease control from each agent alone (P =.038). Administering 4HPR and rituximab
      to mice with established tumors induced complete responses (CRs) in 80% of
      animals compared with 20% to 40% CRs using either agent alone (P =.07), resulting
      in significantly improved survival. Tumors harvested from 4HPR + rituximab
      treated mice displayed elevated caspase activation compared with untreated
      controls (P =.02). Adding a broad-spectrum caspase inhibitor in vivo fully
      abrogated the antitumor effects of 4HPR + rituximab (P =.05). These results
      establish the efficacy of 4HPR/rituximab combinations, confirm their caspase
      mediated mechanism of action, and offer the potential for disease control with
      minimal toxicity for patients with B-cell malignancies.

PMID- 14695241
TI  - Functional characterization of factor V-Ile359Thr: a novel mutation associated
      with thrombosis.
AB  - A missense mutation, FV-Ile359Thr (FV Liverpool), associated with thrombosis has
      recently been described. This mutation creates an additional potential N-linked
      glycosylation site (Asn-X-Ser/Thr) in factor V (FV) at Asn357 that could
      interfere with secretion and/or protein interactions. To investigate the
      molecular pathology of FV-Ile359Thr, the mutation was created by site-directed
      mutagenesis and expressed together with other mutations that could help explain
      the phenotype (FV-Arg306Gln/Ile359Thr/Arg679Gln, FV
      Ile359Thr/Arg506Gln/Arg679Gln, and FV-Asn357Gln/Ile359Thr). The FV-Ile359Thr was
      secreted normally and had full procoagulant activity. Western blot analysis
      showed that FV-Ile359Thr migrated more slowly, while the FV-Asn357Gln/Ile359Thr
      was indistinguishable from FV-wild type (FV-WT), indicating that FV-Ile359Thr was
      expressed with an additional carbohydrate chain. Activated protein C (APC)
      mediated inactivation in an FVa degradation assay showed that the Ile359Thr
      mutation significantly reduced the cleavage at Arg306 both in the presence and
      absence of protein S, whereas the cleavage at Arg506 was unaffected. When tested
      in an FVIIIa degradation assay, the FV-Ile359Thr variant exhibited equally low
      APC cofactor activity as FV Leiden (FVArg506Gln). In conclusion, the Ile359Thr
      mutation appears to affect anticoagulation by 2 mechanisms, impeding the APC
      mediated down-regulation of the FVa molecule and additionally being a poor APC
      cofactor for the down-regulation of FVIIIa. These findings explain the
      association of the FV-Ile359Thr mutation with thrombosis.

PMID- 14695243
TI  - Sorting out the driving forces for parallel and antiparallel alignment in the
      abeta peptide fibril structure.

PMID- 14695244
TI  - Water accessibility, aggregation, and motional features of polysaccharide-protein
      conjugate vaccines.
AB  - A relaxometric investigation of a nontoxic mutant of diphtheria toxin and of its
      conjugates with capsular polysaccharides of different groups of Neisseria
      meningitidis was performed. The insertion of polysaccharides chains alters
      dramatically the hydrodynamic properties of the protein. The model-free analysis
      of the (1)H nuclear magnetic relaxation dispersion profiles of their water
      solutions shows: i), a reduced protein hydration with respect to the carrier
      protein alone; ii), a much larger flexibility of the conjugates with respect to a
      compact macromolecule of the same molecular weight; and iii), a strong tendency
      to aggregate. The above findings are largely independent on the nature of the
      polysaccharide and thus provide a fairly general picture of the dynamic
      properties of glycoconjugate proteins.

PMID- 14695245
TI  - Self-organization of polarized cell signaling via autocrine circuits:
      computational model analysis.
AB  - Recent studies have suggested that autocrine signaling through epidermal growth
      factor receptor (EGFR) might be involved in generating or maintaining an
      intrinsic polarity in tissue cells, possibly via spatial localization of EGFR
      mediated signaling. The difficulty of experimental investigation of autocrine
      signaling makes especially valuable an application of computational modeling for
      critical hypotheses about the dynamic operation of the underlying signaling
      circuits, both intracellular and extracellular. Toward this end, we develop and
      analyze here a spatially distributed dynamic computational model of autocrine
      EGFR signaling. Under certain conditions, the model spontaneously evolves into a
      state wherein sustained signaling is spatially localized on smaller than cell
      dimension, conferring a polarity to the otherwise nonpolar model cell. Conditions
      of a sufficiently large rate of autocrine EGFR ligand release and of a
      sufficiently small exogenous ligand concentration are qualitatively consistent
      with experimental observations of EGFR-mediated migration. Thus, computational
      analysis supports the concept that autocrine EGFR signaling circuits could play a
      role in helping generate and/or maintain an intrinsic cell spatial polarity,
      possibly related to migration as well as tissue organization. We additionally
      offer particular suggestions for critical nodes in the EGFR signaling circuits
      governing this self-organization capability.

PMID- 14695246
TI  - On hydrophobicity and conformational specificity in proteins.
AB  - In this study we examine the distribution of hydrophobic residues in a
      nonredundant set of monomeric globular single-domain proteins. We find that the
      total fraction of hydrophobic residues is roughly constant and has no discernible
      dependence on protein size. This results in a decrease of the hydrophobicity of
      the core as the size of proteins increases. Using a normalized measure, and by
      comparing with sets of randomly reshuffled sequences, we show that this change in
      the composition of the core is statistically significant and robust with respect
      to which amino acids are considered hydrophobic and to how buried residues are
      defined. Comparison with model sequences optimized for stability, while still
      required to retain their native state as a unique minimum energy conformation,
      suggests that the size-independence of the total fraction of hydrophobic residues
      could be a result of requiring proteins to be conformationally specific.

PMID- 14695247
TI  - Assembly and kinetic folding pathways of a tetrameric beta-sheet complex:
      molecular dynamics simulations on simplified off-lattice protein models.
AB  - We have performed discontinuous molecular dynamic simulations of the assembly and
      folding kinetics of a tetrameric beta-sheet complex that contains four identical
      four-stranded antiparallel beta-sheet peptides. The potential used in the
      simulation is a hybrid Go-type potential characterized by the bias gap parameter
      g, an artificial measure of a model protein's preference for its native state,
      and the intermolecular contact parameter eta, which measures the ratio of
      intermolecular to intramolecular native attractions. The formation of the beta
      sheet complex and its equilibrium properties strongly depend on the size of the
      intermolecular contact parameter eta. The ordered beta-sheet complex in the
      folded state and nonaligned beta-sheets or tangled chains in the misfolded state
      are distinguished by measuring the squared radius of gyration Rg2 and the
      fraction of native contacts Q. The folding yield for the folded state is high at
      intermediate values of eta, but is low at both small and large values of eta. The
      folded state at small eta is liquid-like, but is solid-like at both intermediate
      and large eta. The misfolded state at small eta contains nonaligned beta-sheets
      and tangled chains with poor secondary structure at large eta. Various folding
      pathways via dimeric and trimeric intermediates are observed, depending on eta.
      Comparison with experimental results on protein aggregation indicates that
      intermediate eta values are most appropriate for modeling fibril formation and
      small eta values are most appropriate for modeling the formation of amorphous
      aggregates.

PMID- 14695248
TI  - Theory and simulation of water permeation in aquaporin-1.
AB  - We discuss the difference between osmotic permeability pf and diffusion
      permeability pd of single-file water channels and demonstrate that the pf/pd
      ratio corresponds to the number of effective steps a water molecule needs to take
      to permeate a channel. While pd can be directly obtained from equilibrium
      molecular dynamics simulations, pf can be best determined from simulations in
      which a chemical potential difference of water has been established on the two
      sides of the channel. In light of this, we suggest a method to induce in
      molecular dynamics simulations a hydrostatic pressure difference across the
      membrane, from which pf can be measured. Simulations using this method are
      performed on aquaporin-1 channels in a lipid bilayer, resulting in a calculated
      pf of 7.1 x 10(-14) cm(3)/s, which is in close agreement with observation. Using
      a previously determined pd value, we conclude that pf/pd for aquaporin-1 measures
      approximately 12. This number is explained in terms of channel architecture and
      conduction mechanism.

PMID- 14695249
TI  - Sensitivity of OR in phage lambda.
AB  - We investigate the sensitivity of the right operator in bacteriophage lambda. In
      particular, the system is probed in the three different regulatory protein
      concentration-regimes: 1), lysogen (CI dominates); 2), during induction (CI and
      Cro at comparable concentrations); and 3), after induction (Cro dominates).
      Systematic perturbations of the protein-operator binding energies show in a
      lysogen that the activity (production rate) at promoter PRM is robust to
      variations, in contrast to PR, where the sensitivity is high. Both promoters,
      however, show large sensitivity in regimes 2 and 3. In all regimes we identify
      several suppressors, meaning that for a given large perturbation (+/-2 kcal/mol)
      of one binding energy, there exist compensating perturbation(s) that restore the
      wild-type activity.

PMID- 14695250
TI  - Revisiting free energy calculations: a theoretical connection to MM/PBSA and
      direct calculation of the association free energy.
AB  - The prediction of absolute ligand-receptor binding affinities is essential in a
      wide range of biophysical queries, from the study of protein-protein interactions
      to structure-based drug design. End-point free energy methods, such as the
      Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) model, have received
      much attention and widespread application in recent literature. These methods
      benefit from computational efficiency as only the initial and final states of the
      system are evaluated, yet there remains a need for strengthening their
      theoretical foundation. Here a clear connection between statistical
      thermodynamics and end-point free energy models is presented. The importance of
      the association free energy, arising from one molecule's loss of translational
      and rotational freedom from the standard state concentration, is addressed. A
      novel method for calculating this quantity directly from a molecular dynamics
      simulation is described. The challenges of accounting for changes in the protein
      conformation and its fluctuations from separate simulations are discussed. A
      simple first-order approximation of the configuration integral is presented to
      lay the groundwork for future efforts. This model has been applied to FKBP12, a
      small immunophilin that has been widely studied in the drug industry for its
      potential immunosuppressive and neuroregenerative effects.

PMID- 14695251
TI  - Why the lysogenic state of phage lambda is so stable: a mathematical modeling
      approach.
AB  - We develop a mathematical model of the phage lambda lysis/lysogeny switch, taking
      into account recent experimental evidence demonstrating enhanced cooperativity
      between the left and right operator regions. Model parameters are estimated from
      available experimental data. The model is shown to have a single stable steady
      state for these estimated parameter values, and this steady state corresponds to
      the lysogenic state. When the CI degradation rate (gammacI) is slightly increased
      from its normal value (gammacI approximately 0.0 min(-1)), two additional steady
      states appear (through a saddle-node bifurcation) in addition to the lysogenic
      state. One of these new steady states is stable and corresponds to the lytic
      state. The other steady state is an (unstable) saddle node. The coexistence these
      two globally stable steady states (the lytic and lysogenic states) is maintained
      with further increases of gammacI until gammacI approximately 0.35 min(-1), when
      the lysogenic steady state and the saddle node collide and vanish (through a
      reverse saddle node bifurcation) leaving only the lytic state surviving. These
      results allow us to understand the high degree of stability of the lysogenic
      state because, normally, it is the only steady state. Further implications of
      these results for the stability of the phage lambda switch are discussed, as well
      as possible experimental tests of the model.

PMID- 14695252
TI  - Small-world communication of residues and significance for protein dynamics.
AB  - It is not merely the position of residues that is critically important for a
      protein's function and stability, but also their interactions. We illustrate, by
      using a network construction on a set of 595 nonhomologous proteins, that regular
      packing is preserved in short-range interactions, but short average path lengths
      are achieved through some long-range contacts. Thus, lying between the two
      extremes of regularity and randomness, residues in folded proteins are
      distributed according to a "small-world" topology. Using this topology, we show
      that the core residues have the same local packing arrangements irrespective of
      protein size. Furthermore, we find that the average shortest path lengths are
      highly correlated with residue fluctuations, providing a link between the spatial
      arrangement of the residues and protein dynamics.

PMID- 14695253
TI  - Gating gramicidin channels in lipid bilayers: reaction coordinates and the
      mechanism of dissociation.
AB  - The dissociation of gramicidin A (gA) channels into monomers is the simplest
      example of a channel gating process. The initial steps in this process are
      studied via a computational model that simulates the reaction coordinate for
      dimer-monomer dissociation. The nonbonded interaction energy between the monomers
      is determined, allowing for their free relative translational and rotational
      motion. Lowest energy pathways and reaction coordinates of the gating process are
      determined. Partial rupture of the six hydrogen bonds (6HB) at the dimer junction
      takes place by coupling monomer rotation and lateral displacement. Coupling
      rotation with axial separation is far more expensive energetically. The
      transition state for channel dissociation occurs when monomers are displaced
      laterally by approximately 4-6 A, separated by approximately 1.6-2 A, and rotated
      by approximately 120 degrees, breaking two hydrogen bonds. In membranes with
      significant hydrophobic mismatch there is a much greater likelihood of forming
      4HB and possibly even 2HB states. In the 4HB state the pore remains fully open
      and conductive. However, transitions from the 6HB to 4HB and 4HB to 2HB states
      take place via intermediates in which the gA pore is closed and nonconductive.
      These lateral monomer displacements give rise to transitory pore occlusion at the
      dimer junction, which provides a rationale for fast closure events (flickers).
      Local dynamics of gA monomers also leads to lateral and rotational diffusion of
      the whole gA dimer, giving rise to diffusional rotation of the dimer about the
      channel axis.

PMID- 14695254
TI  - Ser and Thr residues modulate the conformation of pro-kinked transmembrane alpha
      helices.
AB  - Functionally required conformational plasticity of transmembrane proteins implies
      that specific structural motifs have been integrated in transmembrane helices.
      Surveying a database of transmembrane helices and the large family of G-protein
      coupled receptors we identified a series of overrepresented motifs associating
      Pro with either Ser or Thr. Thus, we have studied the conformation of Pro-kinked
      transmembrane helices containing Ser or Thr residues, in both g+ and g- rotamers,
      by molecular dynamics simulations in a hydrophobic environment. Analysis of the
      simulations shows that Ser or Thr can significantly modulate the deformation of
      the Pro. A series of motifs, such as (S/T)P and (S/T)AP in the g+ rotamer and the
      TAP and PAA(S/T) motifs in the g- rotamer, induce an increase in bending angle of
      the helix compared to a standard Pro-kink, apparently due to the additional
      hydrogen bond formed between the side chain of Ser/Thr and the backbone carbonyl
      oxygen. In contrast, (S/T)AAP and PA(S/T) motifs, in both g+ and g-, and PAA(S/T)
      in g+ rotamers decrease the bending angle of the helix by either reducing the
      steric clash between the pyrrolidine ring of Pro and the helical backbone, or by
      adding a constrain in the form of a hydrogen bond in the curved-in face of the
      helix. Together with a number of available experimental data, our results
      strongly suggest that association of Ser and Thr with Pro is commonly used in
      transmembrane helices to accommodate the structural needs of specific functions.

PMID- 14695255
TI  - Refinement of F-actin model against fiber diffraction data by long-range normal
      modes.
AB  - The atomic model of F-actin was refined against fiber diffraction data using long
      range normal modes as adjustable parameters to account for the collective long
      range filamentous deformations. To determine the effect of long-range
      deformations on the refinement, each of the four domains of G-actin was treated
      as a rigid body. It was found that among all modes, the bending modes make the
      most significant contributions to the improvement of the refinement. Inclusion of
      only 7-9 bending modes as adjustable parameters yielded a lowest R-factor of
      6.3%. These results demonstrate that employing normal modes as refinement
      parameters has the advantage of using a small number of adjustable parameters to
      achieve a good fitting efficiency. Such a refinement procedure may therefore
      prevent the refinement from overfitting the structural model. More importantly,
      the results of this study demonstrate that, for any fiber diffraction data, a
      substantial amount of refinement error is due to long-range deformations,
      especially the bending, of the filaments. The effects of these intrinsic
      deformations cannot be easily compensated for by adjusting local structural
      parameters, and must be properly accounted for in the refinement to achieve
      improved fit of refined models with experimental diffraction data.

PMID- 14695256
TI  - Glucose accumulation can account for the initial water flux triggered by
      Na+/glucose cotransport.
AB  - Over the last decade, several cotransport studies have led to the proposal of
      secondary active transport of water, challenging the dogma that all water
      transport is passive. The major observation leading to this interpretation was
      that a Na+ influx failed to reproduce the large and rapid cell swelling induced
      by Na+/solute cotransport. We have investigated this phenomenon by comparing a
      Na+/glucose (hSGLT1) induced water flux to water fluxes triggered either by a
      cationic inward current (using ROMK2 K+ channels) or by a glucose influx (using
      GLUT2, a passive glucose transporter). These proteins were overexpressed in
      Xenopus oocytes and assayed through volumetric measurements combined with double
      electrode electrophysiology or radioactive uptake measurements. The osmotic
      gradients driving the observed water fluxes were estimated by comparison with the
      swelling induced by osmotic shocks of known amplitude. We found that, for
      equivalent cation or glucose uptakes, the combination of substrate accumulations
      observed with ROMK2 and GLUT2 are sufficient to provide the osmotic gradient
      necessary to account for a passive water flux through SGLT1. Despite the fact
      that the Na+/glucose stoichiometry of SGLT1 is 2:1, glucose accumulation accounts
      for two-thirds of the osmotic gradient responsible for the water flux observed at
      t = 30 s. It is concluded that the different accumulation processes for neutral
      versus charged solutes can quantitatively account for the fast water flux
      associated with Na+/glucose cotransport activation without having to propose the
      presence of secondary active water transport.

PMID- 14695258
TI  - Diffusion of single cardiac ryanodine receptors in lipid bilayers is decreased by
      annexin 12.
AB  - Diffusion of cardiac ryanodine receptors (RyR2) in lipid bilayers was
      characterized. RyR2 location was monitored by imaging fluo-3 fluorescence due to
      Ca2+ flux through RyR2 channels or fluorescence from RyR2 conjugated with Alexa
      488 or containing green fluorescent protein. Single channel currents were
      recorded to ensure that functional channels were studied. RyR2 exhibited an
      apparent diffusion coefficient (DRyR) of 1.2 x 10(-8) cm2 s(-1) and a mean path
      length of 5.0 microm. Optimal use of optical methods for analysis of RyR2 channel
      function requires that RyR2 diffusion be limited. Therefore, we tested the effect
      of annexin 12, which interacts with anionic phospholipids in a Ca2+-dependent
      manner. Addition of annexin 12 (0.25-4.0 microM) to the trans side of bilayers
      containing an 80:20 ratio of phosphatidylethanolamine/phosphatidylserine
      decreased RyR2 diffusion in a concentration-dependent manner. Annexin 12 (2
      microM) decreased the apparent DRyR 683-fold from 1.2-10(-8) to 1.8 x 10(-11) cm2
      s(-1) and the mean path length 10-fold from 5.0 to 0.5 micro m without obvious
      changes in the conductance of the native bilayer or in activation of RyR2
      channels by Ca2+ or suramin. Thus, annexin 12 may provide a useful tool for
      optimizing optical analysis of RyR2 channels in lipid bilayers.

PMID- 14695257
TI  - Imaging single cardiac ryanodine receptor Ca2+ fluxes in lipid bilayers.
AB  - In this and an accompanying report we describe two steps, single-channel imaging
      and channel immobilization, necessary for using optical imaging to analyze the
      function of ryanodine receptor (RyR) channels reconstituted in lipid bilayers. An
      optical bilayer system capable of laser scanning confocal imaging of fluo-3
      fluorescence due to Ca2+ flux through single RyR2 channels and simultaneous
      recording of single channel currents was developed. A voltage command protocol
      was devised in which the amplitude, time course, shape, and hence the quantity of
      Ca2+ flux through a single RyR2 channel is controlled solely by the voltage
      imposed across the bilayer. Using this system, the voltage command protocol, and
      concentrations of Ca2+ (25-50 mM) that result in saturating RyR2 Ca2+ currents,
      proportional fluo-3 fluorescence was recorded simultaneously with Ca2+ currents
      having amplitudes of 0.25-14 pA. Ca2+ sparks, similar to those obtained with
      conventional microscope-based laser scanning confocal systems, were imaged in
      mouse ventricular cardiomyocytes using the optical bilayer system. The utility of
      the optical bilayer for systematic investigation of how cellular factors
      extrinsic to the RyR2 channel, such as Ca2+ buffers and diffusion, alter fluo-3
      fluorescent responses to RyR2 Ca2+ currents, and for addressing other current
      research questions is discussed.

PMID- 14695259
TI  - The physiological properties of a novel family of VDAC-like proteins from
      Drosophila melanogaster.
AB  - VDAC, a major protein of the mitochondrial outer membrane, forms voltage
      dependent, anion-selective channels permeable to most metabolites. Although
      multiple isoforms of VDAC have been found in different organisms, only one
      isoform (porin/DVDAC) has been previously reported for Drosophila melanogaster.
      We have examined the physiological properties of three other Drosophila proteins
      (CG17137, CG17139, and CG17140) whose primary sequences have significant homology
      to DVDAC. A comparison of their hydropathy profiles (beta-pattern) with known
      VDAC sequences indicates the same fundamental folding pattern but with major
      insertions and deletions. The ability of these proteins to form channels was
      tested on planar membranes and liposomes. Channel activity was observed with
      varying degrees of similarity to VDAC. Two of these proteins (CG17137 and
      CG17140) produced channels with anionic selectivity in the open state. Sometimes
      channels exhibited closure and voltage gating, but for CG17140 this occurred at
      much higher voltages than is typical for VDAC. CG17139 was not able to form
      channels. DVDAC and CG17137 were able to rescue the temperature-sensitive
      conditional-lethal phenotype of VDAC-deficient yeast, whereas CG17139 and CG17140
      demonstrated no complementation. Similar structure and channel formation indicate
      that VDAC-like proteins are part of the larger VDAC family but the modifications
      are indicative of specialized functions.

PMID- 14695260
TI  - Peripheral hot spots for local Ca2+ release after single action potentials in
      sympathetic ganglion neurons.
AB  - Ca2+ release from the endoplasmic reticulum (ER) contributes to Ca2+ transients
      in frog sympathetic ganglion neurons. Here we use video-rate confocal fluo-4
      fluorescence imaging to show that single action potentials reproducibly trigger
      rapidly rising Ca2+ transients at 1-3 local hot spots within the peripheral ER
      rich layer in intact neurons in fresh ganglia and in the majority (74%) of
      cultured neurons. Hot spots were located near the nucleus or the axon hillock
      region. Other regions exhibited either slower and smaller signals or no response.
      Ca2+ signals spread into the cell at constant velocity across the ER in
      nonnuclear regions, indicating active propagation, but spread with a (time)1/2
      dependence within the nucleus, consistent with diffusion. 26% of cultured cells
      exhibited uniform Ca2+ signals around the periphery, but hot spots were produced
      by loading the cytosol with EGTA or by bathing such cells in low-Ca2+ Ringer's
      solution. Peripheral hot spots for Ca2+ release within the perinuclear and axon
      hillock regions provide a mechanism for preferential initiation of nuclear and
      axonal Ca2+ signals by single action potentials in sympathetic ganglion neurons.

PMID- 14695261
TI  - Polymorphism of Ca2+ sparks evoked from in-focus Ca2+ release units in cardiac
      myocytes.
AB  - Ca2+ sparks are the elementary release events in many types of cells. Here we
      present a morphometric analysis of Ca2+ sparks (i.e., amplitude and kinetic
      parameters) using an approach that minimizes the confounding factor of the
      detection of out-of-focus events. By activation and visualization of Ca2+ sparks
      from Ca2+ release units under loose-seal patch-clamp conditions, we found that
      the amplitude and rising rate of in-focus sparks exhibited a broad modal
      distribution, whereas spark rise time and spatial width appeared to be
      stereotyped. Spark morphometrics were constant irrespective of the latency of
      spark production and the time-dependent L-type Ca2+ channel activation.
      Polymorphism of Ca2+ sparks in terms of variable amplitude and rising rate was
      evident for events from the same release units, and intra- and interrelease unit
      variability contributed equally to the overall variability. The rising rate, a
      reporter of the underlying Ca2+ release flux, displayed a strong positive
      correlation with spark amplitude, but a negative correlation with spark rise
      time, an index of Ca2+ release duration. On the basis of Ca2+ spark morphometrics
      measured here, we suggested a model in which cohorts of variable number of
      ryanodine receptors are activated in the genesis of Ca2+ sparks, and the ensuing
      negative feedback overrides the regenerative Ca2+-induced Ca2+ release to
      extinguish the ongoing Ca2+ spark.

PMID- 14695262
TI  - The binding of kappa-Conotoxin PVIIA and fast C-type inactivation of Shaker K+
      channels are mutually exclusive.
AB  - Kappa-conotoxin PVIIA (kappa-PVIIA), a 27-amino acid peptide identified from the
      venom of Conus purpurascens, inhibits the Shaker K+ channel by blocking its outer
      pore. The toxin appears as a gating modifier because its binding affinity
      decreases with relatively fast kinetics upon channel opening, but there is no
      indication that it interferes with the gating transitions of the wild-type
      channels (WT), including the structural changes of the outer pore that underlie
      its slow C-type inactivation. In this report we demonstrate that in two outer
      pore mutants of Shaker-IR (M448K and T449S), that have high toxin sensitivity and
      fast C-type inactivation, the latter process is instead antagonized by and
      incompatible with kappa-PVIIA binding. Inactivation is slowed by the necessary
      preliminary unbinding of kappa-PVIIA, whereas toxin rebinding must await recovery
      from inactivation causing a double-exponential relaxation of the second response
      to double-pulse stimulations. Compared with the lack of similar effects in WT,
      these results demonstrate the ability of peptide toxins like kappa-PVIIA to
      reveal possibly subtle differences in structural changes of the outer pore of K+
      channels; however, they also warn against a naive use of fast inactivating
      mutants as models for C-type inactivation. Unfolded from the antagonistic effect
      of inactivation, toxin binding to mutant noninactivated channels shows state- and
      voltage-dependencies similar to WT: slow and high affinity for closed channels;
      relatively fast dissociation from open channels at rate increasing with voltage.
      This supports the idea that these properties depend mainly on interactions with
      pore-permeation processes that are not affected by the mutations. In mutant
      channels the state-dependence also greatly enhances the protection of toxin
      binding against steady-state inactivation at low depolarizations while still
      allowing large responses to depolarizing pulses that relieve toxin block.
      Although not obviously applicable to any known combination of natural channel and
      outer-pore blocker, our biophysical characterization of such highly efficient
      mechanism of protection from steady-state outer-pore inactivation may be of
      general interest.

PMID- 14695263
TI  - N-type inactivation features of Kv4.2 channel gating.
AB  - We examined whether the N-terminus of Kv4.2 A-type channels (4.2NT) possesses an
      autoinhibitory N-terminal peptide domain, which, similar to the one of Shaker,
      mediates inactivation of the open state. We found that chimeric Kv2.1(4.2NT)
      channels, where the cytoplasmic Kv2.1 N-terminus had been replaced by
      corresponding Kv4.2 domains, inactivated relatively fast, with a mean time
      constant of 120 ms as compared to 3.4 s in Kv2.1 wild-type. Notably, Kv2.1(4.2NT)
      showed features typically observed for Shaker N-type inactivation: fast
      inactivation of Kv2.1(4.2NT) channels was slowed by intracellular
      tetraethylammonium and removed by N-terminal truncation (Delta40). Kv2.1(4.2NT)
      channels reopened during recovery from inactivation, and recovery was accelerated
      in high external K+. Moreover, the application of synthetic N-terminal Kv4.2 and
      ShB peptides to inside-out patches containing slowly inactivating Kv2.1 channels
      mimicked N-type inactivation. Kv4.2 channels, after fractional inactivation,
      mediated tail currents with biphasic decay, indicative of passage through the
      open state during recovery from inactivation. Biphasic tail current kinetics were
      less prominent in Kv4.2/KChIP2.1 channel complexes and virtually absent in
      Kv4.2Delta40 channels. N-type inactivation features of Kv4.2 open-state
      inactivation, which may be suppressed by KChIP association, were also revealed by
      the finding that application of Kv4.2 N-terminal peptide accelerated the decay
      kinetics of both Kv4.2Delta40 and Kv4.2/KChIP2.1 patch currents. However, double
      mutant cycle analysis of N-terminal inactivating and pore domains indicated
      differences in the energetics and structural determinants between Kv4.2 and
      Shaker N-type inactivation.

PMID- 14695264
TI  - Histidines are responsible for zinc potentiation of the current in KDC1 carrot
      channels.
AB  - Unlike all plant inward-rectifying potassium channels, the carrot channel KDC1
      has two histidine pairs (H161,H162) in the S3-S4 and (H224,H225) in the S5-S6
      linkers. When coinjected with KAT1 in Xenopus oocytes, KDC1 participates in the
      formation of heteromultimeric KDC1:KAT1 channels and the ionic current is
      potentiated by extracellular Zn2+. To investigate the potential interactions
      between KDC1 and zinc, a KDC1-KAT1 dimer was constructed. The dimeric and
      heteromeric channels displayed similar characteristics and the same sensitivity
      to zinc and other metals; this result suggests that zinc binding is mediated by
      residues in a single channel subunit. The KDC1:KAT1 currents were also
      potentiated by external Pb2+ and Cd2+ and inhibited by Ni2+. To investigate
      further the role of KDC1-histidines, these amino acids were mutated into
      alanines. The single mutations H225A, H161A, and H162A did not affect the
      response of the heteromeric channels to zinc. Conversely, the single mutant H224A
      and the double mutants (H224A,H225A) and (H161A,H162A) abolished zinc
      potentiation, but not that induced by Pb2+ or Cd2+. These results suggest that
      Zn2+ potentiation cannot be ascribed to simple electrostatic interactions between
      zinc and channel residues and that histidine 224 is crucial for zinc but not for
      lead potentiation of the current.

PMID- 14695265
TI  - Facilitated lactate transport by MCT1 when coexpressed with the sodium
      bicarbonate cotransporter (NBC) in Xenopus oocytes.
AB  - Monocarboxylate transporters (MCT) and sodium-bicarbonate cotransporters (NBC)
      transport acid/base equivalents and coexist in many epithelial and glial cells.
      In nervous systems, the electroneutral MCT1 isoform cotransports lactate and
      other monocarboxylates with H+, and is believed to be involved in the shuttling
      of energy-rich substrates between astrocytes and neurons. The NBC cotransports
      bicarbonate with sodium and generates a membrane current. We have expressed these
      transporter proteins, cloned from rat brain (MCT1) and human kidney (NBC), alone
      and together, by injecting the cRNA into oocytes of the frog Xenopus laevis, and
      measured intracellular pH changes and membrane currents under voltage-clamp with
      intracellular microelectrodes, and radiolabeled lactate uptake into the oocytes.
      We determined the cytosolic buffer capacity, the H+ and lactate fluxes as induced
      by 3 and 10 mM lactate in oocytes expressing MCT1 and/or NBC, and in water
      injected oocytes, in salines buffered with 5 mM HEPES alone or with 5% CO2/10 mM
      HCO3(-) (pH 7.0). In MCT1 + NBC- but not in MCT1- or NBC-expressing oocytes,
      lactate activated a Na+- and HCO3(-)-dependent membrane current, indicating that
      lactate/H+ cotransport via MCT1, due to the induced pH change, stimulates NBC
      activity. Lactate/H+ cotransport by MCT1 was increased about twofold when MCT1
      was expressed together with NBC. Our results suggest that the facilitation of
      MCT1 transport activity is mainly due to the increase in apparent buffer capacity
      contributed by the NBC, and thereby suppresses the build-up of intracellular H+
      during the influx of lactate/H+, which would reduce MCT1 activity. Hence these
      membrane transporters functionally cooperate and are able to increase
      ion/metabolite transport activity.

PMID- 14695266
TI  - Conformational changes in alamethicin associated with substitution of its alpha
      methylalanines with leucines: a FTIR spectroscopic analysis and correlation with
      channel kinetics.
AB  - Alamethicin, a 20 residue-long peptaibol remains a favorite high voltage
      dependent channel-forming peptide. However, the structural significance of its
      abundant noncoded residues (alpha-methylalanine or Aib) for its ion channel
      activity remains unknown, although a previous study showed that replacement of
      all Aib residues with leucines preserved the essential channel behavior except
      for much faster single-channel events. To correlate these functional properties
      with structural data, here we compare the secondary structures of an alamethicin
      derivative where all the eight Aibs were replaced by leucines and the native
      alamethicin. Fourier transform infrared (FTIR) spectra of these peptides were
      recorded in methanol and in aqueous phospholipid membranes. Results obtained show
      a significant conformational change in alamethicin upon substitution of its Aib
      residues with Leu. The amide I band occurs at a lower frequency for the Leu
      derivative indicating that its alpha-helices are involved in stronger hydrogen
      bonding. In addition, the structure of the Leu-derivative is quite sensitive to
      membrane fluidity changes. The amide I band shifts to higher frequencies when the
      lipids are in the fluid phase. This indicates either a decreased solvation due to
      a more complete peptide insertion or a peptide stretching to match the full
      thickness of the bilayer. These results contribute to explain the fast single
      channel kinetics displayed by the Leu-derivative.

PMID- 14695267
TI  - Interaction of the protein transduction domain of HIV-1 TAT with heparan sulfate:
      binding mechanism and thermodynamic parameters.
AB  - The positively charged protein transduction domain of the HIV-1 TAT protein (TAT
      PTD; residues 47-57 of TAT) rapidly translocates across the plasma membrane of
      living cells. This property is exploited for the delivery of proteins, drugs, and
      genes into cells. The mechanism of this translocation is, however, not yet
      understood. Recent theories for translocation suggest binding of the protein
      transduction domain (PTD) to extracellular glycosaminoglycans as a possible
      mechanism. We have studied the binding equilibrium between TAT-PTD and three
      different glycosaminoglycans with high sensitivity isothermal titration
      calorimetry and provide the first quantitative thermodynamic description. The
      polysulfonated macromolecules were found to exhibit multiple identical binding
      sites for TAT-PTD with only small differences between the three species as far as
      the thermodynamic parameters are concerned. Heparan sulfate (HS, molecular
      weight, 14.2 +/- 2 kDa) has 6.3 +/- 1.0 independent binding sites for TAT-PTD
      which are characterized by a binding constant K0 = (6.0 +/- 0.6) x 10(5) M(-1)
      and a reaction enthalpy deltaHpep0 = -4.6 +/- 1.0 kcal/mol at 28 degrees C. The
      binding affinity, deltaGpep0, is determined to equal extent by enthalpic and
      entropic contributions. The HS-TAT-PTD complex formation entails a positive heat
      capacity change of deltaCp0 = +135 cal/mol peptide, which is characteristic of a
      charge neutralization reaction. This is in contrast to hydrophobic binding
      reactions which display a large negative heat capacity change. The stoichiometry
      of 6-7 TAT-PTD molecules per HS corresponds to an electric charge neutralization.
      Light scattering data demonstrate a maximum scattering intensity at this
      stoichiometric ratio, the intensity of which depends on the order of mixing of
      the two components. The data suggest cross-linking and/or aggregation of HS-TAT
      PTD complexes. Two other glycosaminoglycans, namely heparin and chondroitin
      sulfate B, were also studied with isothermal titration calorimetry. The
      thermodynamic parameters are K0 = (6.0 +/- 0.8) x 10(5) M(-1) and kcal/mol for
      heparin and K0 = (2.5 +/- 0.5) x 10(5) M(-1) and kcal/mol for chondroitin sulfate
      B at 28 degrees C. The close thermodynamic similarity of the three binding
      molecules also implies a close structural relationship. The ubiquitous occurrence
      of glycosaminoglycans on the cell surface together with their tight and rapid
      interaction with the TAT protein transduction domain makes complex formation a
      strong candidate as the primary step of protein translocation.

PMID- 14695268
TI  - Lateral ordering of lipid chains in cholesterol-containing membranes: high-field
      spin-label EPR.
AB  - High-field (i.e., 94 GHz) electron paramagnetic resonance is used to characterize
      the nonaxial ordering of spin-labeled lipid chains in membranes containing
      cholesterol. Employing high magnetic fields (and microwave frequencies) allows
      investigation of both the lateral and transverse ordering of the phospholipid
      chains by cholesterol, from the x-y and z-elements, respectively, of the spin
      label g-tensor. Transverse ordering is described by the conventional order
      parameter, <P2(cosbeta)>, where beta is the instantaneous inclination of the
      chain axis to the membrane normal; and lateral ordering is described by the order
      parameter <cos2(phi - phi)>, where phi is the azimuthal angle about the chain
      axis and phi is the mean azimuthal orientation about which angular fluctuations
      take place. To obtain high positional resolution, phosphatidylcholines spin
      labeled at all odd and even positions from n = 4 to n = 14 in the sn-2 chain (1
      acyl-2-[n-(4,4'-dimethyloxazolidine-N-oxyl)]stearoyl-sn-glycero-3-phosphocholine)
      are used at probe amounts in membranes of dimyristoyl phosphatidylcholine
      containing either high (40 mol %) or low (5 mol %) concentrations of cholesterol.
      At high-cholesterol content, lateral ordering of the spin-labeled lipid chains is
      detected over a wide range of temperature throughout the liquid-ordered phase.
      The transverse profile of lateral phi-ordering with position, n, of chain
      labeling follows the profile of the rigid steroid nucleus of cholesterol. It
      becomes progressively averaged toward the terminal methyl group of the sn-2
      chain, in the region of the flexible hydrocarbon chain of cholesterol. At low
      cholesterol content, lateral chain ordering is prominent at low temperature, but
      diminishes at progressively higher chain positions with increasing temperature.
      The nonaxial lipid ordering may be related to the formation of in-plane lipid
      domains in membranes containing cholesterol and saturated lipids.

PMID- 14695269
TI  - Oligomerization of fusogenic peptides promotes membrane fusion by enhancing
      membrane destabilization.
AB  - A key element of membrane fusion reactions in biology is the involvement of
      specific fusion proteins. In many viruses, the proteins that mediate membrane
      fusion usually exist as homotrimers. Furthermore, they contain extended triple
      helical coiled-coil domains and fusogenic peptides. It has been suggested that
      the coiled-coil domains present the fusogenic peptide in a conformation or
      geometry favorable for membrane fusion. To test the hypothesis that trimerization
      of fusogenic peptide is related to optimal fusion, we have designed and
      synthesized a triple-stranded coiled-coil X31 peptide, also known as the ccX31,
      which mimics the influenza virus hemagglutinin fusion peptide in the fusion
      active state. We compared the membrane interactive properties of ccX31 versus the
      monomeric X31 fusogenic peptide. Our data show that trimerization enhances
      peptide-induced leakage of liposomal contents and lipid mixing. Furthermore,
      studies using micropipette aspiration of single vesicles reveal that ccX31
      decreases lysis tension, tau(lysis), but not area expansion modulus, Ka, of
      phospholipid bilayers, whereas monomeric X31 peptide lowers both tau(lysis) and
      Ka. Our results are consistent with the hypothesis that oligomerization of
      fusogenic peptide promotes membrane fusion, possibly by enhancing localized
      destabilization of lipid bilayers.

PMID- 14695270
TI  - Electric field-induced changes in lipids investigated by modulated excitation
      FTIR spectroscopy.
AB  - The effect of electric fields on dry oriented multibilayers of
      dimyristoylphosphatidylcholine (DMPC) was investigated by transmission Fourier
      transform infrared electric field modulated excitation (E-ME) spectroscopy. A
      periodic rectangular electric potential (0-150 V, 1.25 Hz, 28.4 degrees C +/- 0.2
      degrees C) was applied across the sample. To discriminate electric field-induced
      effects from possible temperature-induced effects resulting from a current flow
      (<1 pA) across the sample, corresponding temperature-modulated excitation (T-ME)
      measurements within the temperature uncertainty limits of +/-0.2 degrees C at
      28.4 degrees C were performed. T-ME induced reversible gauche defects in the
      hydrocarbon chains, whereas E-ME resulted in reversible compression of dry DMPC
      bilayers. Periodic variation of the tilt angle of the hydrocarbon chains is
      suggested. The degree of absorbance modulation in the CH-stretching region was
      found to be in the order of 1:700, corresponding to a variation of the bilayer
      thickness of Deltaz = 0.0054 nm. Using a series connection of capacitors as
      equivalent circuit of the cell resulted in E = (1.2 +/- 0.7) x 10(7) V/m for the
      electric field in DMPC. Young's elasticity modulus of DMPC could be calculated to
      be E( perpendicular ) = 2.2 x 10(6) Pa +/- 1.8 x 10(6) Pa, which is in good
      agreement with published data obtained by electric field-dependent capacitance
      measurements.

PMID- 14695271
TI  - A lipid-specific toxin reveals heterogeneity of sphingomyelin-containing
      membranes.
AB  - Little is known about the heterogenous organization of lipids in biological
      membranes. Sphingomyelin (SM) is a major plasma membrane lipid that forms lipid
      domains together with cholesterol and glycolipids. Using SM-specific toxin,
      lysenin, we showed that in cultured epithelial cells the accessibility of the
      toxin to SM is different between apical and basolateral membranes. Apical
      membranes are highly enriched with glycolipids. The inhibitory role of
      glycolipids in the binding of lysenin to SM was confirmed by comparing the
      glycolipid-deficient mutant melanoma cell line with its parent cell. Model
      membrane experiments indicated that glycolipid altered the local density of SM so
      that the affinity of the lipid for lysenin was decreased. Our results indicate
      that lysenin recognizes the heterogenous organization of SM in biomembranes and
      that the organization of SM differs between different cell types and between
      different membrane domains within the same cell. Isothermal titration calorimetry
      suggests that lysenin binding to SM is presumably the result of a SM-lysenin
      complex formation of specific stoichiometry, thus supporting the idea of the
      existence of small condensed lipid complexes consisting of just a few lipid
      molecules in living cells.

PMID- 14695272
TI  - Effect of pulmonary surfactant protein SP-B on the micro- and nanostructure of
      phospholipid films.
AB  - Monolayers of dipalmitoylphosphatidylcholine (DPPC) and
      DPPC/dipalmitoylphosphatidylglycerol (DPPG) (7:3, w/w) in the absence or in the
      presence of 2, 5, 10, or 20 weight percent of porcine surfactant protein SP-B
      were spread at the air-liquid interface of a surface balance, compressed up to
      surface pressures in the liquid-expanded/liquid-condensed (LE-LC) plateau of the
      isotherm, transferred onto mica supports, and analyzed by scanning force
      microscopy. In the absence of protein, the films showed micrometer-sized
      condensed domains with morphology and size that were analogous to those observed
      in situ at the air-liquid interface by epifluorescence microscopy. Scanning force
      microscopy permits examination of the coexisting phases at a higher resolution
      than previously achieved with fluorescent microscopy. Both LE and LC regions of
      DPPC films were heterogeneous in nature. LC microdomains contained numerous
      expanded-like islands whereas regions apparently liquid-expanded were covered by
      a condensed-like framework of interconnected nanodomains. Presence of increasing
      amounts of pulmonary surfactant protein SP-B affected the distribution of the LE
      and LC regions of DPPC and DPPC/DPPG films both at the microscopic and the
      nanoscopic level. The condensed microdomains became more numerous but their size
      decreased, resulting in an overall reduction of the amount of total LC phase in
      both DPPC and DPPC/DPPG films. At the nanoscopic level, SP-B also caused a marked
      reduction of the size of the condensed-like nanodomains in the LE phase and an
      increase in the length of the LE/LC interface. SP-B promotes a fine nanoscopic
      framework of lipid and lipid-protein nanodomains that is associated with a
      substantial mechanical resistance to film deformation and rupture as observed
      during film transference and manipulation. The effect of SP-B on the nanoscopic
      structure of the lipid films was greater in DPPC/DPPG than in pure DPPC films,
      indicating additional contributions of electrostatic lipid-protein interactions.
      The alterations of the nanoscopic structures of phospholipid films by SP-B
      provide the structural framework for the protein simultaneously sustaining
      structural stability as well as dynamical flexibility in surfactant films at the
      extreme conditions imposed by the respiratory mechanics. SP-B also formed
      segregated two-dimensional clusters that were associated with the boundaries
      between LC microdomains and the LE regions of DPPC and DPPC/DPPG films. The
      presence of these clusters at protein-to-lipid proportions above 2% by weight
      suggests that the concentration of SP-B in the surfactant lipid-protein complexes
      may be close to the solubility limit of the protein in the lipid films.

PMID- 14695273
TI  - Distribution of GD3 in DPPC monolayers: a thermodynamic and atomic force
      microscopy combined study.
AB  - Gangliosides are the main component of lipid rafts. These microdomains, floating
      in the outer leaflet of cellular membrane, play a key role in fundamental
      cellular functions. Little is still known about ganglioside and phospholipid
      interaction. We studied mixtures of dipalmitoylphosphatidylcholine and GD3 (molar
      fraction of 0.2, 0.4, 0.6, 0.8) using complementary techniques: 1), thermodynamic
      properties of the Langmuir-Blodgett films were assessed at the air-water
      interface (surface tension, surface potential); and 2), three-dimensional
      morphology of deposited films on mica substrates were imaged by atomic force
      microscopy. Mixture thermodynamics were consistent with data in the literature.
      In particular, excess free energy was negative at each molar fraction, thus
      ruling out GD3 segregation. Atomic force microscopy showed that the height of
      liquid-condensed domains in deposited films varied with GD3 molar fraction, as
      compatible with a lipid aggregation model proposed by Maggio. No distinct GD3
      rich domain was observed inside the films, suggesting that GD3 molecules
      gradually mix with dipalmitoylphosphatidylcholine molecules, confirming DeltaG
      data. Morphological analysis revealed that the shape of liquid-condensed domains
      is strongly influenced by the amount of GD3, and an interesting stripe-formation
      phenomenon was observed. These data were combined with the thermodynamic results
      and interpreted in the light of McConnell's model.

PMID- 14695274
TI  - Membrane binding, structure, and localization of cecropin-mellitin hybrid
      peptides: a site-directed spin-labeling study.
AB  - The interaction of antimicrobial peptides with membranes is a key factor in
      determining their biological activity. In this study we have synthesized a series
      of minimized cecropin-mellitin hybrid peptides each containing a single cysteine
      residue, modified the cysteine with the sulfhydryl-specific methanethiosulfonate
      spin-label, and used electron paramagnetic resonance spectroscopy to measure
      membrane-binding affinities and determine the orientation and localization of
      peptides bound to membranes that mimic the bacterial cytoplasmic membrane. All of
      the peptides were unstructured in aqueous solution but underwent a significant
      conformational change upon membrane binding that diminished the rotational
      mobility of the attached spin-label. Apparent partition coefficients were similar
      for five of the six constructs examined, indicating that location of the spin
      label had little effect on peptide binding as long as the attachment site was in
      the relatively hydrophobic C-terminal domain. Depth measurements based on
      accessibility of the spin-labeled sites to oxygen and nickel
      ethylenediaminediacetate indicated that at high lipid/peptide ratios these
      peptides form a single alpha-helix, with the helical axis aligned parallel to the
      bilayer surface and immersed approximately 5 A below the membrane-aqueous
      interface. Such a localization would provide exposure of charged/polar residues
      on the hydrophilic face of the amphipathic helix to the aqueous phase, and allow
      the nonpolar residues along the opposite face of the helix to remain immersed in
      the hydrophobic phase of the bilayer. These results are discussed with respect to
      the mechanism of membrane disruption by antimicrobial peptides.

PMID- 14695275
TI  - Distribution of pentachlorophenol in phospholipid bilayers: a molecular dynamics
      study.
AB  - Molecular dynamics computer simulations of pentachlorophenol (PCP) in palmitoyl
      oleoyl-phosphatidylethanolamine and palmitoyl-oleoyl-phosphatidylcholine lipid
      bilayers were carried out to investigate the distribution of PCP and the effects
      of PCP on the phospholipid bilayer structure. Starting from two extreme starting
      structures, including PCP molecules outside the lipid bilayer, the PCP
      distribution converges in simulations of up to 50 ns. PCP preferentially occupies
      the region between the carbonyl groups and the double bonds in the acyl chains of
      the lipid molecules in the bilayer. In the presence of PCP, the lipid chain order
      increases somewhat in both chains, and the average tilt angle of the lipid chains
      decreases. The increase in the lipid chain order in the presence of PCP was more
      pronounced in the palmitoyl-oleoyl-phosphatidylcholine bilayer compared to the
      palmitoyl-oleoyl-phosphatidylethanolamine bilayer. The number of trans
      conformations of lipid chain dihedrals does not change significantly. PCP aligns
      parallel to the alkyl chains of the lipid to optimize the packing in the dense
      ordered chain region of the bilayer. The hydroxyl group of PCP forms hydrogen
      bonds with both water and lipid oxygen atoms in the water/lipid interface region.

PMID- 14695276
TI  - Diameter oscillation of axonemes in sea-urchin sperm flagella.
AB  - The 9 + 2 configuration of axonemes is one of the most conserved structures of
      eukaryotic organelles. Evidence so far has confirmed that bending of cilia and
      flagella is the result of active sliding of microtubules induced by dynein arms.
      If the conformational change of dynein motors, which would be a key step of force
      generation, is occurring in a three-dimensional manner, we can easily expect that
      the microtubule sliding should contain some transverse component, i.e., a motion
      in a direction at a right angle to the longitudinal axis of axonemes. Using a
      modified technique of atomic force microscopy, we found such transverse motion is
      actually occurring in an oscillatory manner when the axonemes of sea-urchin sperm
      flagella were adhered onto glass substrates. The motion was adenosine
      triphosphate-dependent and the observed frequency of oscillation was similar to
      that of oscillatory sliding of microtubules that had been shown to reflect the
      physiological activity of dynein arms (S. Kamimura and R. Kamiya. 1989. Nature:
      340:476-478; 1992. J. Cell Biol. 116:1443-1454). Maximal amplitude of the
      diameter oscillation was around 10 nm, which was within a range of morphological
      change observed with electron microscopy (F. D. Warner. 1978. J. Cell Biol.
      77:R19-R26; N. C. Zanetti, D. R. Mitchell, and F. D. Warner. 1979. J. Cell Biol.
      80:573-588).

PMID- 14695277
TI  - Stepwise sliding of single actin and Myosin filaments.
AB  - Dynamics of sliding were explored in isolated actin and myosin filaments. Sliding
      occurs in steps. The steps are integer multiples of 2.7 nm, which is equal to the
      monomeric repeat along the actin filament. When filaments were forced to slide in
      the reverse direction, the size paradigm was the same. This size paradigm is
      parallel to that seen in the kinesin-microtubule system, where step size is an
      integer multiple of the tubulin repeat along the microtubule.

PMID- 14695278
TI  - Interplay of troponin- and Myosin-based pathways of calcium activation in
      skeletal and cardiac muscle: the use of W7 as an inhibitor of thin filament
      activation.
AB  - To investigate the interplay between the thin and thick filaments during calcium
      activation in striated muscle, we employed n-(6-aminohexyl) 5-chloro-1
      napthalenesulfonamide (W7) as an inhibitor of troponin C and compared its effects
      with that of the myosin-specific inhibitor, 2,3-butanedione 2-monoxime (BDM). In
      both skeletal and cardiac fibers, W7 reversibly inhibited ATPase and tension over
      the full range of calcium activation between pCa 8.0 and 4.5, resulting in
      reduced calcium sensitivity and cooperativity of ATPase and tension activations.
      At maximal activation in skeletal fibers, the W7 concentrations for half-maximal
      inhibition (KI) were 70-80 micro M for ATPase and 20-30 micro M for tension,
      nearly >200-fold lower than BDM (20 mM and 5-8 mM, respectively). When W7 (50
      microM) and BDM (20 mM) were combined in skeletal fibers, the ATPase and tension
      pCa curves exhibited lower apparent cooperativity and maxima and higher calcium
      sensitivity than expected from two independent activation pathways, suggesting
      that the interplay between the thin and thick filaments varies with the level of
      activation. Significantly, the inhibition of W7 increased the ATPase/tension
      ratio during activation in both muscle types. W7 holds much promise as a potent
      and reversible inhibitor of thin filament-mediated calcium activation of skeletal
      and cardiac muscle contraction.

PMID- 14695279
TI  - Comparison of the effect of water release on the interaction of the Saccharomyces
      cerevisiae TATA binding protein (TBP) with "TATA Box" sequences composed of
      adenosine or inosine.
AB  - The formation of sequence-specific complexes of TATA binding protein (TBP) with
      the minor groove of DNA results in the burial of large nonpolar surfaces and the
      exclusion of water from these interfaces. The release of water is thus expected
      to provide a significant entropic driving force for formation of the
      transcription-preinitiated complexes mediated by the binding of TBP to specific
      sequences. In this article are described equilibrium-binding studies of
      Saccharomyces cerevisiae TBP to 14 bp oligonucleotides bearing either the tightly
      bound and efficiently transcribed adenovirus major late promoter (TATAAAAG) or
      its inosine-substituted derivative (TITIIIIG) as a function of neutral osmolyte
      concentration. These two DNA sequences present the same pattern of minor groove
      hydrogen-bond donors and acceptors to the protein. TBP-DNA complex formation was
      monitored by steady-state fluorescence resonance energy transfer measurements of
      the oligonucleotides end-labeled with fluorescein (donor) and TAMRA (acceptor).
      Correct interpretation of the results obtained with the inosine-substituted
      sequence required careful consideration of the optical properties of the dyes as
      a function of osmolyte concentration to demonstrate that the relative change in
      the end-to-end distances for TATAAAAG- and TITIIIIG-bearing oligonucleotides is
      the same upon TBP binding. Although the affinity of TBP is slightly greater for
      the adenosine compared with the inosine-substituted TATA sequence in the absence
      of osmolyte, the end-to-end distances of the bound DNA in complex with TBP, the
      enthalpic and electrostatic components of binding, are identical within
      experimental precision. However, approximately 18 additional molecules of water
      are released upon TBP binding the TATAAAAG as compared with the TITIIIIG sequence
      resulting in an entropic advantage to the binding of the natural promoter
      sequence. These results are considered with regard to differences in the
      flexibility and hydration of the two DNA sequences.

PMID- 14695280
TI  - Photodynamics of red fluorescent proteins studied by fluorescence correlation
      spectroscopy.
AB  - Red fluorescent proteins are important tools in fluorescence-based life science
      research. Recently, we have introduced eqFP611, a red fluorescent protein with
      advantageous properties from the sea anemone Entacmaea quadricolor. Here, we have
      studied the submillisecond light-driven intramolecular dynamics between bright
      and dark states of eqFP611 and, for comparison, drFP583 (DsRed) by using
      fluorescence correlation spectroscopy on protein solutions. A three-state model
      with one dark and two fluorescent states describes the power-dependence of the
      flickering dynamics of both proteins at different excitation wavelengths. It
      involves two light-driven conformational transitions. We have also studied the
      photodynamics of individual (monomeric) eqFP611 molecules immobilized on
      surfaces. The flickering rates and dark state fractions of eqFP611 bound to
      polyethylene glycol-covered glass surfaces were identical to those measured in
      solution, showing that the bound FPs behaved identically. A second, much slower
      flickering process was observed on the 10-ms timescale. Deposition of eqFP611
      molecules on bare glass surfaces yielded bright fluorescence without any
      detectable flickering and a >10-fold decreased photobleaching yield. These
      observations underscore the intimate connection between protein motions and
      photophysical processes in fluorescent proteins.

PMID- 14695281
TI  - Phosphorylation-dependent changes in structure and dynamics in ERK2 detected by
      SDSL and EPR.
AB  - Mitogen-activated protein kinases are regulated by occupancy at two
      phosphorylation sites near the active site cleft. Previous studies using hydrogen
      exchange to investigate the canonical mitogen-activated protein kinase,
      extracellular signal-regulated protein kinase-2, have shown that phosphorylation
      alters backbone conformational mobility >10 A distal to the site of
      phosphorylation, including decreased mobility within amino acids 102-105 and
      increased mobility within 108-109. To further describe changes after enzyme
      activation, site-directed spin labeling at amino acids 101, 105-109, 111, 112 and
      electron paramagnetic resonance spectroscopy were used to investigate this
      region. The anisotropic hyperfine splitting of the spin labels in glassy samples
      was unchanged by phosphorylation, consistent with previous crystallographic
      studies that indicate no structural change in this region. At positions 101, 111,
      and 112, the mobility of the spin label was unchanged by diphosphorylation,
      consistent with little or no conformational change. However, diphosphorylation
      caused small but significant changes in rotational diffusion rates at positions
      105-108 and altered proportions of probe in a motionally constrained state at
      positions 105, 107, and 109. Thus, electron paramagnetic resonance indicates
      reproducible changes in nanosecond side-chain mobilities at specific residues
      within the interdomain region, far from the site of phosphorylation and
      conformational change.

PMID- 14695282
TI  - Protein fiber linear dichroism for structure determination and kinetics in a low
      volume, low-wavelength couette flow cell.
AB  - High-resolution structure determination of soluble globular proteins relies
      heavily on x-ray crystallography techniques. Such an approach is often
      ineffective for investigations into the structure of fibrous proteins as these
      proteins generally do not crystallize. Thus investigations into fibrous protein
      structure have relied on less direct methods such as x-ray fiber diffraction and
      circular dichroism. Ultraviolet linear dichroism has the potential to provide
      additional information on the structure of such biomolecular systems. However,
      existing systems are not optimized for the requirements of fibrous proteins. We
      have designed and built a low-volume (200 microL), low-wavelength (down to 180
      nm), low-pathlength (100 microm), high-alignment flow-alignment system (couette)
      to perform ultraviolet linear dichroism studies on the fibers formed by a range
      of biomolecules. The apparatus has been tested using a number of proteins for
      which longer wavelength linear dichroism spectra had already been measured. The
      new couette cell has also been used to obtain data on two medically important
      protein fibers, the all-beta-sheet amyloid fibers of the Alzheimer's derived
      protein Abeta and the long-chain assemblies of alpha1-antitrypsin polymers.

PMID- 14695283
TI  - An optimal structure-discriminative amino acid index for protein fold
      recognition.
AB  - Identifying the fold class of a protein sequence of unknown structure is a
      fundamental problem in modern biology. We apply a supervised learning algorithm
      to the classification of protein sequences with low sequence identity from a
      library of 174 structural classes created with the Combinatorial Extension
      structural alignment methodology. A class of rules is considered that assigns
      test sequences to structural classes based on the closest match of an amino acid
      index profile of the test sequence to a profile centroid for each class. A
      mathematical optimization procedure is applied to determine an amino acid index
      of maximal structural discriminatory power by maximizing the ratio of between
      class to within-class profile variation. The optimal index is computed as the
      solution to a generalized eigenvalue problem, and its performance for fold
      classification is compared to that of other published indices. The optimal index
      has significantly more structural discriminatory power than all currently known
      indices, including average surrounding hydrophobicity, which it most closely
      resembles. It demonstrates >70% classification accuracy over all folds and nearly
      100% accuracy on several folds with distinctive conserved structural features.
      Finally, there is a compelling universality to the optimal index in that it does
      not appear to depend strongly on the specific structural classes used in its
      computation.

PMID- 14695284
TI  - Crystal structure of the hyperthermophilic inorganic pyrophosphatase from the
      archaeon Pyrococcus horikoshii.
AB  - A homolog to the eubacteria inorganic pyrophosphatase (PPase, EC 3.6.1.1) was
      found in the genome of the hyperthermophilic archaeon Pyrococcus horikoshii. This
      inorganic pyrophosphatase (Pho-PPase) grows optimally at 88 degrees C. To
      understand the structural basis for the thermostability of Pho-PPase, we have
      determined the crystal structure to 2.66 A resolution. The crystallographic
      asymmetric unit contains three monomers related by approximate threefold
      symmetry, and a hexamer is built up by twofold crystallographic symmetry. The
      main-chain fold of Pho-PPase is almost identical to that of the known crystal
      structure of the model from Sulfolobus acidocaldarius. A detailed comparison of
      the crystal structure of Pho-PPase with related structures from S.
      acidocaldarius, Thermus thermophilus, and Escherichia coli shows significant
      differences that may account for the difference in their thermostabilities. A
      reduction in thermolabile residues, additional aromatic residues, and more
      intimate association between subunits all contribute to the larger
      thermophilicity of Pho-PPase. In particular, deletions in two loops surrounding
      the active site help to stabilize its conformation, while ion-pair networks
      unique to Pho-PPase are located in the active site and near the C-terminus. The
      identification of structural features that make PPases more adaptable to extreme
      temperature should prove helpful for future biotechnology applications.

PMID- 14695285
TI  - Increasing the amphiphilicity of an amyloidogenic peptide changes the beta-sheet
      structure in the fibrils from antiparallel to parallel.
AB  - Solid-state NMR measurements have been reported for four peptides derived from
      beta-amyloid peptide Abeta(1-42): Abeta(1-40), Abeta(10-35), Abeta(16-22), and
      Abeta(34-42). Of these, the first two are predicted to be amphiphilic and were
      reported to form parallel beta-sheets, whereas the latter two peptides appear
      nonamphiphilic and adopt an antiparallel beta-sheet organization. These results
      suggest that amphiphilicity may be significant in determining fibril structure.
      Here, we demonstrate that acylation of Abeta(16-22) with octanoic acid increases
      its amphiphilicity and changes the organization of fibrillar beta-sheet from
      antiparallel to parallel. Electron microscopy, Congo Red binding, and one
      dimensional 13C NMR measurements demonstrate that octanoyl-Abeta(16-22) forms
      typical amyloid fibrils. Based on the stability of monolayers at the air-water
      interface, octanoyl-Abeta(16-22) is more amphiphilic than Abeta(16-22).
      Measurements of 13C-13C and 15N-13C nuclear magnetic dipole-dipole couplings in
      isotopically labeled fibril samples, using the constant-time finite-pulse
      radiofrequency-driven recoupling (fpRFDR-CT) and rotational echo double resonance
      (REDOR) solid-state NMR techniques, demonstrate that octanoyl-Abeta(16-22)
      fibrils are composed of parallel beta-sheets, whereas Abeta(16-22) fibrils are
      composed of antiparallel beta-sheets. These data demonstrate that amphiphilicity
      is critical in determining the structural organization of beta-sheets in the
      amyloid fibril. This work also shows that all amyloid fibrils do not share a
      common supramolecular structure, and suggests a method for controlling the
      structure of amyloid fibrils.

PMID- 14695286
TI  - Competition with xenon elicits ligand migration and escape pathways in myoglobin.
AB  - Evidence for ligand migration toward the xenon-binding cavities in myoglobin
      comes from a number of laser photolysis studies of MbO2 including mutants and
      from cryo- and time-resolved crystallography of MbCO. To explore ligand migration
      in greater detail, we investigated the rebinding kinetics of both MbO2 and MbCO
      under a xenon partial pressure ranging from 1 to 16 atm over the temperature
      range (293-77 K). Below 180 K xenon affects to a significant, but minor, extent
      the thermodynamic parameters for rebinding from the primary docking site in each
      Mb taxonomic substate. Above 200 K the ligand migrates to the proximal Xe1 site
      but when the latter is occupied by xenon a new kinetic process appears. It is
      attributed to rebinding from transient docking sites located on the path between
      the primary and the secondary docking site of both ligands. Ligand escape
      exhibits a more complicated pattern than expected. At room temperature O2 and CO
      escape appears to take place exclusively from the primary site. In contrast, at T
      approximately 250 K, roughly 50% of the CO molecules that have escaped from the
      protein originate from the Xe1 secondary site.

PMID- 14695287
TI  - Proton linkage for CO binding and redox properties of bovine lactoperoxidase.
AB  - The pH-dependence of redox properties and of CO binding to bovine lactoperoxidase
      has been investigated over the range between 2 and 11. The pH-dependence of redox
      potentials shows a biphasic behavior, suggesting the existence of (at least) two
      redox-linked groups, which change their pKa values upon reduction. These values
      are in close agreement with those observed to play a relevant role in the
      modulation of CO binding to ferrous bovine lactoperoxidase. They have been
      tentatively attributed to Arg-372 and His-226, which are located on the distal
      side of the heme pocket of lactoperoxidase. A complete and unequivocal
      description of the proton-linked behavior of bovine lactoperoxidase requires,
      however, three residues, which are redox linked and relevant for the modulation
      of CO binding. The rate constant for CO binding to bovine lactoperoxidase is
      slower than what is reported for most hemoproteins, suggesting that these two
      residues, Arg-372 and His-226, are representing a severe barrier for the access
      of exogenous ligands to the heme. This aspect has been further investigated by
      fast kinetics following laser photolysis, trying to obtain information on the
      ligand binding pathway and on the energy barriers.

PMID- 14695288
TI  - Small angle x-ray scattering from lipid-bound myelin basic protein in solution.
AB  - The structure of myelin basic protein (MBP), purified from the myelin sheath in
      both lipid-free (LF-MBP) and lipid-bound (LB-MBP) forms, was investigated in
      solution by small angle x-ray scattering. The water-soluble LF-MBP, extracted at
      pH < 3.0 from defatted brain, is the classical preparation of MBP, commonly
      regarded as an intrinsically unfolded protein. LB-MBP is a lipoprotein-detergent
      complex extracted from myelin with its native lipidic environment at pH > 7.0.
      Under all conditions, the scattering from the two protein forms was different,
      indicating different molecular shapes. For the LB-MBP, well-defined scattering
      curves were obtained, suggesting that the protein had a unique, compact (but not
      globular) structure. Furthermore, these data were compatible with earlier results
      from molecular modeling calculations on the MBP structure which have been refined
      by us. In contrast, the LF-MBP data were in accordance with the expected open
      coil conformation. The results represent the first direct structural information
      from x-ray scattering measurements on MBP in its native lipidic environment in
      solution.

PMID- 14695289
TI  - Interactions of the neurotoxin vipoxin in solution studied by dynamic light
      scattering.
AB  - The neurotoxin vipoxin is the lethal component of the venom of Vipera ammodytes
      meridionalis. It is a heterodimer of a basic toxic His-48 phospholipase A2 (PLA2)
      and an acidic nontoxic Gln-48 PLA2. The shape of the neurotoxin and its separated
      components in solution as well as their interactions with calcium, the brain
      phospholipid phosphatidylcholine, and two inhibitors, elaidoylamide and vitamin
      E, were investigated by dynamic light scattering. Calcium binding is connected
      with a conformational change in vipoxin observed as a change of the hydrodynamic
      shape from oblate ellipsoid to a shape closer to a sphere. The Ca2+-bound form of
      vipoxin, which is catalytically active, is more compact and symmetric than the
      calcium-free heterodimer. Similar changes were observed as a result of the Ca2+
      binding to the two separated subunits. In the presence of aggregated
      phosphatidylcholine, the neurotoxic complex dissociates to subunits. It is
      supposed that only the toxic component binds to the substrate, and the other
      subunit, which plays a chaperone function, remains in solution. The inhibition of
      vipoxin with the synthetic inhibitor elaidoylamide and the natural compound
      vitamin E changes the shape of the toxin from oblate to prolate ellipsoid. The
      inhibited toxin is more asymmetric in comparison to the native one. Similar, but
      not so pronounced, effects were observed after the inhibition of the monomeric
      and homodimeric forms of the toxic His-48 PLA2. Circular dichroism measurements
      in the presence of urea, methylurea, and ethylurea indicate a strong hydrophobic
      stabilization of the neurotoxin. Hydrophobic interactions stabilize not only the
      folded regions but also the regions of intersubunit contacts.

PMID- 14695290
TI  - Molecular probes: what is the range of their interaction with the environment?
AB  - We performed pressure-tuning hole-burning experiments on a modified cytochrome c
      protein in a glycerol/buffer glass. The shift and the broadening of the holes
      were investigated for various frequencies within the inhomogeneous band. On the
      basis of a simple model, we were able to estimate the interaction range between
      chromophore and protein. It is approximately 4.5 A. The parameters that enter the
      model are the compressibility, the static mean-square displacement, the
      inhomogeneous width, and the average spectral shift per pressure. From this
      result and from our experiments on pressure-induced denaturing, we conclude that
      water molecules have to be brought very close to the chromophore during the
      denaturation process.

PMID- 14695291
TI  - Electrospray ionization-mass spectrometry and tandem mass spectrometry reveal
      self-association and metal-ion binding of hydrophobic peptides: a study of the
      gramicidin dimer.
AB  - Gramicidin is a membrane pentadecapeptide that acts as a channel, allowing the
      passage of monovalent metal ions and assisting in bacterial cell death. The
      active form is a noncovalently bound dimer. One means to study the self-assembly
      of this peptide has been to compare the state of the peptide in various solvents
      ranging from hydrophilic (e.g., trifluoroethanol) to hydrophobic (e.g., n
      propanol). In this article, we report the use of electrospray mass spectrometry
      to study the self-association of gramicidin in various organic and mixed solvents
      that are introduced directly into the mass spectrometer. The dimer (both homo and
      hetero) can survive the introduction into the gas phase, and the amount in the
      gas phase increases with the decreasing dielectric constant of the solvent,
      reflecting solution-phase behavior. Tandem mass spectrometry data reveal that the
      stability of dimer in the gas phase decreases with increasing metal ion size,
      strongly suggesting that the metal ion binds inside the dimer between the
      monomers.

PMID- 14695292
TI  - Picosecond internal dynamics of lysozyme as affected by thermal unfolding in
      nonaqueous environment.
AB  - A neutron-scattering investigation of the internal picosecond dynamics of
      lysozyme solvated in glycerol as a function of temperature in the range 200-410 K
      has been undertaken. The inelastic contribution to the measured intensity is
      characterized by the presence of a bump generally known as "boson peak", clearly
      distinguishable at low temperature. When the temperature is increased the
      quasielastic component of the spectrum becomes more and more intrusive and
      progressively overwhelms the vibrational bump. This happens especially for T >
      345 K when the protein goes through an unfolding process, which leads to the
      complete denaturation. The quasielastic term is the superposition of two
      components whose intensities and linewidths have been studied as a function of
      temperature. The slower component describes motions with characteristic times of
      approximately 4 ps corresponding to reorientations of polypeptide side chains.
      Both the intensity and linewidth of this kind of relaxations show two distinct
      regimes with a crossover in the temperature range where the melting process
      occurs, thus suggesting the presence of a dynamical transition correlated to the
      protein unfolding. Conversely the faster component might be ascribed to the local
      dynamics of hydrogen atoms caged by the nearest neighbors with characteristic
      time of approximately 0.3 ps.

PMID- 14695293
TI  - Theoretical and experimental study of the D2194G mutation in the C2 domain of
      coagulation factor V.
AB  - Coagulation factor V (FV) is a large plasma glycoprotein with functions in both
      the pro- and anticoagulant pathways. In carriers of the so-called R2-FV
      haplotype, the FV D2194G mutation, in the C2 membrane-binding domain, is
      associated with low expression levels, suggesting a potential folding/stability
      problem. To analyze the molecular mechanisms potentially responsible for this in
      vitro phenotype, we used molecular dynamics (MD) and continuum electrostatic
      calculations. Implicit solvent simulations were performed on the x-ray structure
      of the wild-type C2 domain and on a model of the D2194G mutant. Because D2194 is
      located next to a disulfide bond (S-S bond), MD calculations were also performed
      on S-S bond depleted structures. D2194 is part of a salt-bridge network and
      investigations of the stabilizing/destabilizing role of these ionic interactions
      were carried out. Five mutant FV molecules were created and the expression levels
      measured with the aim of assessing the tolerance to amino acid changes in this
      region of molecule. Analysis of the MD trajectories indicated increased
      flexibility in some areas and energetic comparisons suggested overall
      destabilization of the structure due to the D2194G mutation. This substitution
      causes electrostatic destabilization of the domain by approximately 3 kcal/mol.
      Together these effects likely explain the lowered expression levels in R2-FV
      carriers.

PMID- 14695294
TI  - Subunit structure of gas vesicles: a MALDI-TOF mass spectrometry study.
AB  - Many aquatic microorganisms use gas vesicles to regulate their depth in the water
      column. The molecular basis for the novel physical properties of these floatation
      organelles remains mysterious due to the inapplicability of either solution or
      single crystal structural methods. In the present study, some folding constraints
      for the approximately 7-kDa GvpA building blocks of the vesicles are established
      via matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      studies of intact and proteolyzed vesicles from the cyanobacterium Anabaena flos
      aquae and the archaea Halobacterium salinarum. The spectra of undigested vesicles
      show no evidence of posttranslational modification of the GvpA. The extent of
      carboxypeptidase digestion shows that the alanine rich C-terminal pentapeptide of
      GvpA is exposed to the surface in both organisms. The bonds that are cleaved by
      Trypsin and GluC are exclusively in the extended N-terminus of the Anabaena flos
      aquae protein and in the extended C-terminus of the Halobacterium salinarum
      protein. All the potentially cleavable peptide bonds in the central, highly
      conserved portion of the protein appear to be shielded from protease attack in
      spite of the fact that some of the corresponding side chains are almost certainly
      exposed to the aqueous medium.

PMID- 14695295
TI  - Triple-color coincidence analysis: one step further in following higher order
      molecular complex formation.
AB  - Confocal fluorescence spectroscopy is a versatile method for studying dynamics
      and interactions of biomolecules in their native environment with minimal
      interference with the observed system. Analyzing coincident fluctuations induced
      by single molecule movement in spectrally distinct detection channels, dual-color
      fluorescence cross-correlation, and coincidence analysis have proven most
      powerful for probing the formation or cleavage of molecular bonds in real time.
      The similarity of the optical setup with those used for laser scanning
      microscopy, as well as the non-invasiveness of the methods, make them easily
      adaptive for intracellular measurements, to observe the association and
      dissociation of biomolecules in situ. However, in contrast to standard
      fluorescence microscopy, where multiple fluorophores can be spectrally resolved,
      single molecule detection has so far been limited to dual-color detection systems
      due to the harsh requirements on detection sensitivity. In this study, we show
      that under certain experimental conditions, employing simultaneous two-photon
      excitation of three distinct dye species, their successful discrimination indeed
      becomes possible even on a single molecule level. This enables the direct
      observation of higher order molecular complex formation in the confocal volume.
      The theoretical concept of triple-color coincidence analysis is outlined in
      detail, along with an experimental demonstration of its principles utilizing a
      simple nucleic acid reaction system.

PMID- 14695296
TI  - Characterization by atomic force microscopy of Alzheimer paired helical filaments
      under physiological conditions.
AB  - Paired helical filaments (PHF) is an aberrant structure present in the brain of
      Alzheimer's disease patients which has been correlated with their degree of
      dementia. In order to determine the structure of PHF, several studies have been
      performed using atomic force microscopy (AFM). However, those studies have the
      limitation that they have not been done in solution and the sample could be far
      from the real physiological conditions. In this work we present an AFM analysis
      of PHF in liquid environment and we compare that analysis with that performed in
      dry conditions. PHF imaging in liquid was only possible by using jumping mode AFM
      as the imaging technique. Jumping mode AFM images of PHF in solution show first,
      a notable increase in the absolute values of the height of the filament, and
      second, a smaller ratio between the height measured at the upper and at the lower
      part of the PHF. Direct comparison of the experimental data with structural
      models has been performed. From this we conclude that the PHF structure is
      compatible with two coupled ribbons with an overall height of 20 nm and a width
      of 10 nm.

PMID- 14695297
TI  - Structural characterization of siliceous spicules from marine sponges.
AB  - Siliceous sponges, one of the few animal groups involved in a biosilicification
      process, deposit hydrated silica in discrete skeletal elements called spicules. A
      multidisciplinary analysis of the structural features of the protein axial
      filaments inside the spicules of a number of marine sponges, belonging to two
      different classes (Demospongiae and Hexactinellida), is presented, together with
      a preliminary analysis of the biosilicification process. The study was carried
      out by a unique combination of techniques: fiber diffraction using synchrotron
      radiation, scanning electron microscopy (SEM), thermogravimetric analysis (TGA),
      differential scanning calorimetric (DSC), Fourier transform infrared spectroscopy
      (FTIR), and molecular modeling. From a phylogenetic point of view, the main
      result is the structural difference between the dimension and packing of the
      protein units in the spicule filaments of the Demospongiae and the Hexactinellida
      species. Models of the protein organization in the spicule axial filaments,
      consistent with the various experimental evidences, are given. The three
      different species of demosponges analyzed have similar general structural
      features, but they differ in the degree of order. The structural information on
      the spicule axial filaments can help shed some light on the still unknown
      molecular mechanisms controlling biosilicification.

PMID- 14695298
TI  - Measuring hearing organ vibration patterns with confocal microscopy and optical
      flow.
AB  - A new method for visualizing vibrating structures is described. The system
      provides a means to capture very fast repeating events by relatively minor
      modifications to a standard confocal microscope. An acousto-optic modulator was
      inserted in the beam path, generating brief pulses of laser light. Images were
      formed by summing consecutive frames until every pixel of the resulting image had
      been exposed to a laser pulse. Images were analyzed using a new method for
      optical flow computation; it was validated through introducing artificial
      displacements in confocal images. Displacements in the range of 0.8 to 4 pixels
      were measured with 5% error or better. The lower limit for reliable motion
      detection was 20% of the pixel size. These methods were used for investigating
      the motion pattern of the vibrating hearing organ. In contrast to standard
      theory, we show that the organ of Corti possesses several degrees of freedom
      during sound-evoked vibration. Outer hair cells showed motion indicative of
      deformation. After acoustic overstimulation, supporting cells contracted. This
      slowly developing structural change was visualized during simultaneous intense
      sound stimulation and its speed measured with the optical flow technique.

PMID- 14695299
TI  - The molecular mechanics of P- and L-selectin lectin domains binding to PSGL-1.
AB  - A laser trap was used to compare the load-dependent binding kinetics between
      truncated P- and L-selectin to their natural ligand, P-selectin glycoprotein
      ligand-1 (PSGL-1) over the predicted physiological range of loading rates. Human
      PSGL-1 was covalently coupled to polystyrene beads. Chimeric selectins were
      adsorbed to nitrocellulose-coated glass beads on a coverslip. A PSGL-1 bead was
      held in a laser trap and touched to a vertical surface of the glass bead,
      allowing a bond to form between selectin and ligand. The surface was moved away
      from the microsphere, applying load at a constant rate until bond rupture.
      Rupture force for both selectins increased with loading rate, but significant
      differences in rupture force between P- and L-selectin were observed only above
      460 pN/s. These data are best represented as two energy barriers to unbinding,
      with the transition from the low to high loading rate regime at 260-290 pN/s. The
      data also allow the first estimate of a two-dimensional specific on-rate for
      binding of these two selectins to their natural ligand (1.7 microm2/s). These
      data suggest that P- and L-selectin lectin domains have very similar kinetics
      under physiological conditions.

PMID- 14695300
TI  - The connection between chromatin motion on the 100 nm length scale and core
      histone dynamics in live XTC-2 cells and isolated nuclei.
AB  - The diffusive motion of DNA-containing chromatin in live cells and isolated
      nuclei is investigated using a two-photon standing wave fluorescence
      photobleaching experiment with 100 nm spatial resolution. The chromatin is
      labeled using the minor groove binding dye Hoechst 33342. In live cells, the mean
      diffusion rate is 5 x 10(-4) micro m2/s, with considerable cell-to-cell
      variation. This diffusion is highly constrained and cannot be observed in a
      standard, single beam fluorescence recovery after photobleaching experiment. To
      determine the chemical origin of the diffusion, we study motion in isolated
      nuclei and vary the strength of the histone-DNA interactions by changing the
      ionic strength and using chemical and photocross-linking experiments. At higher
      NaCl concentrations, we see increased chromatin diffusion as the histone-DNA
      interaction is weakened due to ionic screening, whereas photocross-linking the
      core histones to the DNA results in a complete absence of diffusive motion. These
      trends are consistent with the 100 nm scale motion being correlated with the
      interactions of histone proteins with the DNA. If chromatin diffusion is
      connected to the nucleosomal dynamics on much smaller length scales, this may
      provide a way to assay biochemical activity in vivo based on larger scale
      macromolecular dynamics observed via fluorescence microscopy.

PMID- 14695301
TI  - Hydrogen-deuterium exchange effects on beta-endorphin release from AtT20 murine
      pituitary tumor cells.
AB  - Abundant evidences demonstrate that deuterium oxide (D2O) modulates various
      secretory activities, but specific mechanisms remain unclear. Using AtT20 cells,
      we examined effects of D2O on physiological processes underlying beta-endorphin
      release. Immunofluorescent confocal microscopy demonstrated that 90% D2O buffer
      increased the amount of actin filament in cell somas and decreased it in cell
      processes, whereas beta-tubulin was not affected. Ca2+ imaging demonstrated that
      high-K+-induced Ca2+ influx was not affected during D2O treatment, but was
      completely inhibited upon D2O washout. The H2O/D2O replacement in internal
      solutions of patch electrodes reduced Ca2+ currents evoked by depolarizing
      voltage steps, whereas additional extracellular H2O/D2O replacement recovered the
      currents, suggesting that D2O gradient across plasma membrane is critical for
      Ca2+ channel kinetics. Radioimmunoassay of high-K+-induced beta-endorphin release
      demonstrated an increase during D2O treatment and a decrease upon D(2)O washout.
      These results demonstrate that the H2O-to-D2O-induced increase in beta-endorphin
      release corresponded with the redistribution of actin, and the D2O-to-H2O-induced
      decrease in beta-endorphin release corresponded with the inhibition of voltage
      sensitive Ca2+ channels. The computer modeling suggests that the differences in
      the zero-point vibrational energy between protonated and deuterated amino acids
      produce an asymmetric distribution of these amino acids upon D2O washout and this
      causes the dysfunction of Ca2+ channels.

PMID- 14695302
TI  - Hydrodynamic forces applied on intercellular bonds, soluble molecules, and cell
      surface receptors.
AB  - Cells and biomolecules exposed to blood circulation experience hydrodynamic
      forces that affect their function. We present a methodology to estimate fluid
      forces and force loading rates applied on cellular aggregates, cell-surface
      proteins, and soluble molecules. Low Reynolds-number hydrodynamic theory is
      employed. Selected results are presented for biological cases involving
      platelets, neutrophils, tumor cells, GpIb-like cell-surface receptors, and plasma
      von Willebrand factor (vWF)-like soluble proteins. Calculations reveal the
      following: 1), upon application of constant linear shear, cell aggregates and
      biomolecules experience time-varying forces due to their tumbling motion. 2), In
      comparison to neutrophil homotypic aggregates, the maximum force applied on
      neutrophil-platelet aggregates is approximately threefold lower. Thus,
      alterations in cell size may dramatically alter adhesion molecule requirement for
      efficient cell binding. Whereas peak forces on homotypic cell doublets are
      tensile, shear forces dominate in heterotypic doublets with radius ratio <0.3.
      3), The peak forces on platelet GpIb and von Willebrand factor are of comparable
      magnitude. However, they are orders-of-magnitude lower than those applied on
      intercellular bonds. Charts are provided to rapidly evaluate the magnitude of
      hydrodynamic force and rotation time-period occurring in any given experiment.
      The calculation scheme may find application in studies of vascular biology and
      receptor biophysics.

PMID- 14695303
TI  - Spatial analysis of 3' phosphoinositide signaling in living fibroblasts: I.
      Uniform stimulation model and bounds on dimensionless groups.
AB  - Fluorescent protein probes now permit spatial distributions of specific
      intracellular signaling molecules to be observed in real time. Mathematical
      models have been used to simulate molecular gradients and other spatial patterns
      within cells, and the output of such models may be compared directly with
      experiments if the binding of the fluorescent probe and the physics of the
      imaging technique are each incorporated. Here we present a comprehensive model
      describing the dynamics of 3' phosphoinositides (PIs), lipid second messengers
      produced in the plasma membrane in response to stimulation of the PI 3-kinase
      signaling pathway, as monitored in the cell-substratum contact area using total
      internal reflection fluorescence microscopy. With this technique it was
      previously shown that uniform stimulation of fibroblasts with platelet-derived
      growth factor elicits the formation of axisymmetric 3' PI gradients, which we now
      characterize in the context of our model. We find that upper and lower bounds on
      the relevant dimensionless model parameter values for an individual cell can be
      calculated from four well-defined fluorescence measurements. Based on our
      analysis, we expect that the key dimensionless group, the ratio of 3' PI turnover
      and diffusion rates, can be estimated within approximately 20% or less.

PMID- 14695304
TI  - Spatial analysis of 3' phosphoinositide signaling in living fibroblasts: II.
      Parameter estimates for individual cells from experiments.
AB  - Fibroblast migration is directed by gradients of platelet-derived growth factor
      (PDGF) during wound healing. As in other chemotactic systems, it has been shown
      recently that localized stimulation of intracellular phosphoinositide (PI) 3
      kinase activity and production of 3' PI lipids in the plasma membrane are
      important events in the signaling of spatially biased motility processes. In
      turn, 3' PI localization depends on the effective diffusion coefficient, D, and
      turnover rate constant, k, of these lipids. Here we present a systematic and
      direct comparison of mathematical model calculations and experimental
      measurements to estimate the values of the effective 3' PI diffusion coefficient,
      D, turnover rate constant, k, and other parameters in individual fibroblasts
      stimulated uniformly with PDGF. In the context of our uniform stimulation model,
      the values of D and k in each cell were typically estimated within 10-20% or
      less, and the mean values across all of the cells analyzed were D = 0.37 +/- 0.25
      microm2/s and k = 1.18 +/- 0.54 min(-1). In addition, we report that 3' PI
      turnover is not affected by PDGF receptor signaling in our cells, allowing us to
      focus our attention on the regulation of 3' PI production as this system is
      studied further.

PMID- 14695305
TI  - Single-molecule imaging of the H-ras membrane-anchor reveals domains in the
      cytoplasmic leaflet of the cell membrane.
AB  - In the last decade evidence has accumulated that small domains of 50-700 nm in
      diameter are located in the exoplasmic leaflet of the plasma membrane. Most of
      these domains supposedly consist of specific sets of lipids and proteins, and are
      believed to coordinate signal transduction cascades. Whether similar domains are
      also present in the cytoplasmic leaflet of the plasma membrane is unclear so far.
      To investigate the presence of cytoplasmic leaflet domains, the H-Ras membrane
      targeting sequence was fused to the C-terminus of the enhanced yellow fluorescent
      protein. Using single-molecule fluorescence microscopy, trajectories of
      individual molecules diffusing in the cytoplasmic leaflet of the plasma membrane
      were recorded. From these trajectories, the diffusion of individual membrane
      anchored enhanced yellow fluorescent protein molecules was studied in live cells
      on timescales from 5 to 200 ms. The results show that the diffusion of 30-40% of
      the molecules is constrained in domains with a typical size of 200 nm. Neither
      breakdown of actin nor cholesterol extraction changed the domain characteristics
      significantly, indicating that the observed domains may not be related to the
      membrane domains identified so far.

PMID- 14695306
TI  - Substrate compliance versus ligand density in cell on gel responses.
AB  - Substrate stiffness is emerging as an important physical factor in the response
      of many cell types. In agreement with findings on other anchorage-dependent cell
      lineages, aortic smooth muscle cells are found to spread and organize their
      cytoskeleton and focal adhesions much more so on "rigid" glass or "stiff" gels
      than on "soft" gels. Whereas these cells generally show maximal spreading on
      intermediate collagen densities, the limited spreading on soft gels is
      surprisingly insensitive to adhesive ligand density. Bell-shaped cell spreading
      curves encompassing all substrates are modeled by simple functions that couple
      ligand density to substrate stiffness. Although smooth muscle cells spread
      minimally on soft gels regardless of collagen, GFP-actin gives a slight
      overexpression of total actin that can override the soft gel response and drive
      spreading; GFP and GFP-paxillin do not have the same effect. The GFP-actin cells
      invariably show an organized filamentous cytoskeleton and clearly indicate that
      the cytoskeleton is at least one structural node in a signaling network that can
      override spreading limits typically dictated by soft gels. Based on such results,
      we hypothesize a central structural role for the cytoskeleton in driving the
      membrane outward during spreading whereas adhesion reinforces the spreading.

PMID- 14695307
TI  - NADH enzyme-dependent fluorescence recovery after photobleaching (ED-FRAP):
      applications to enzyme and mitochondrial reaction kinetics, in vitro.
AB  - NADH enzyme-dependent fluorescence recovery after photobleaching (ED-FRAP) was
      evaluated for studying enzyme kinetics in vitro and in isolated mitochondria.
      Mass, optical, and nuclear magnetic resonance spectroscopy data were consistent
      with the UV NADH photolysis reaction being NADH --> NAD* + H+ + e-. The overall
      net reaction was O2 + 2NADH + 2H+ --> 2NAD+ + 2H2O, or in the presence of other
      competing electron acceptors such as cytochrome c, NADH + 2Cyt(ox) --> NAD+ + H+
      + 2Cyt(red). Solution pH could differentiate between these free-radical
      scavenging pathways. These net reactions represent the photooxidation of NADH to
      NAD+. Kinetic models and acquisition schemes were developed, varying [NADH] and
      [NAD] by altering NADH photolysis levels, for extracting kinetic parameters. UV
      irradiation levels used did not damage mitochondrial function or enzymatic
      activity. In mitochondria, [NADH] is a high affinity product inhibitor that
      significantly reduced the NADH regeneration rate. Matrix NADH regeneration only
      slightly exceeded the net rate of NADH consumption, suggesting that the NADH
      regeneration process is far from equilibrium. Evaluation of NADH regeneration in
      active mitochondria, in comparison to rotenone-treated preparations, revealed
      other regulatory elements in addition to matrix [NADH] and [NAD] that have yet to
      be fully characterized. These studies demonstrate that the rapid UV photolysis of
      NADH to NAD is an effective tool in evaluating the steady-state kinetic
      properties of enzyme systems. Initial data support the notion that the NADH
      regeneration process is far from equilibrium in mitochondria and is potentially
      controlled by NADH levels as well as several other matrix factors.

PMID- 14695308
TI  - Synaptic integration in electrically coupled neurons.
AB  - Interactions among chemical and electrical synapses regulate the patterns of
      electrical activity of vertebrate and invertebrate neurons. In this investigation
      we studied how electrical coupling influences the integration of excitatory
      postsynaptic potentials (EPSPs). Pairs of Retzius neurons of the leech are
      coupled by a nonrectifying electrical synapse by which chemically induced
      synaptic currents flow from one neuron to the other. Results from
      electrophysiology and modeling suggest that chemical synaptic inputs are located
      on the coupled neurites, at 7.5 microm from the electrical synapses. We also
      showed that the space constant of the coupled neurites was 100 microm,
      approximately twice their length, allowing the efficient spread of synaptic
      currents all along both coupled neurites. Based on this cytoarchitecture, our
      main finding was that the degree of electrical coupling modulates the amplitude
      of EPSPs in the driving neurite by regulating the leak of synaptic current to the
      coupled neurite, so that the amplitude of EPSPs in the driving neurite was
      proportional to the value of the coupling resistance. In contrast, synaptic
      currents arriving at the coupled neurite through the electrical synapse produced
      EPSPs of constant amplitude. This was because the coupling resistance value had
      inverse effects on the amount of current arriving and on the impedance of the
      neurite. We propose that by modulating the amplitude of EPSPs, electrical
      synapses could regulate the firing frequency of neurons.

PMID- 14695309
TI  - Temperature dependence of the iron-histidine resonance Raman band of deoxyheme
      proteins: anharmonic coupling versus distribution over taxonomic conformational
      substates.

PMID- 14695312
TI  - Endoplasmic reticulum stress and unfolded protein response in inclusion body
      myositis muscle.
AB  - Proteins in the endoplasmic reticulum (ER) require an efficient system of
      molecular chaperones whose role is to assure their proper folding and to prevent
      accumulation of unfolded proteins. The response of cells to accumulation of
      unfolded proteins in the ER is termed "unfolded protein response" (UPR). UPR is a
      functional mechanism by which cells attempt to protect themselves against ER
      stress, resulting from the accumulation of the unfolded/misfolded proteins.
      Because intracellular inclusions, containing either amyloid-beta (Abeta) or
      phosphorylated tau, are the characteristic feature of sporadic inclusion body
      myositis (s-IBM) muscle biopsies, we studied expression and immunolocalization of
      five ER chaperones, calnexin, calreticulin, GRP94, BiP/GRP78, and ERp72, in s-IBM
      and control muscle biopsies. Physical interaction of the ER chaperones with
      amyloid-beta precursor protein (AbetaPP) was studied by a combined
      immunoprecipitation/immunoblotting technique in s-IBM and control muscle
      biopsies, and in AbetaPP-overexpressing cultured human muscle fibers. In all s
      IBM muscle biopsies, all five of the ER chaperones were immunodetected in the
      form of inclusions that co-localized with amyloid-beta. By immunoblotting,
      expression of ER chaperones was greatly increased as compared to the controls. By
      immunoprecipitation/immunoblotting experiments, ER chaperones co
      immunoprecipitated with AbetaPP. Our studies provide evidence of the UPR in s-IBM
      muscle and demonstrate for the first time that the ER chaperones calnexin,
      calreticulin, GRP94, BiP/GRP78, and ERp72 physically associate with AbetaPP in s
      IBM muscle, suggesting their playing a role in AbetaPP folding and processing.

PMID- 14695313
TI  - Multi-platform, multi-site, microarray-based human tumor classification.
AB  - The introduction of gene expression profiling has resulted in the production of
      rich human data sets with potential for deciphering tumor diagnosis, prognosis,
      and therapy. Here we demonstrate how artificial neural networks (ANNs) can be
      applied to two completely different microarray platforms (cDNA and
      oligonucleotide), or a combination of both, to build tumor classifiers capable of
      deciphering the identity of most human cancers. First, 78 tumors representing
      eight different types of histologically similar adenocarcinoma, were evaluated
      with a 32k cDNA microarray and correctly classified by a cDNA-based ANN, using
      independent training and test sets, with a mean accuracy of 83%. To expand our
      approach, oligonucleotide data derived from six independent performance sites,
      representing 463 tumors and 21 tumor types, were assembled, normalized, and
      scaled. An oligonucleotide-based ANN, trained on a random fraction of the tumors
      (n = 343), was 88% accurate in predicting known pathological origin of the
      remaining fraction of tumors (n = 120) not exposed to the training algorithm.
      Finally, a mixed-platform classifier using a combination of both cDNA and
      oligonucleotide microarray data from seven performance sites, normalized and
      scaled from a large and diverse tumor set (n = 539), produced similar results
      (85% accuracy) on independent test sets. Further validation of our classifiers
      was achieved by accurately (84%) predicting the known primary site of origin for
      an independent set of metastatic lesions (n = 50), resected from brain, lung, and
      liver, potentially addressing the vexing classification problems imposed by
      unknown primary cancers. These cDNA- and oligonucleotide-based classifiers
      provide a first proof of principle that data derived from multiple platforms and
      performance sites can be exploited to build multi-tissue tumor classifiers.

PMID- 14695314
TI  - Biallelic inactivation of fumarate hydratase (FH) occurs in nonsyndromic uterine
      leiomyomas but is rare in other tumors.
AB  - Germline mutations in the fumarate hydratase (FH) gene at 1q43 predispose to
      dominantly inherited cutaneous and uterine leiomyomas, uterine leiomyosarcoma,
      and papillary renal cell cancer (HLRCC syndrome). To evaluate the role of FH
      inactivation in sporadic tumorigenesis, we analyzed a series of 299 malignant
      tumors representing 10 different malignant tumor types for FH mutations.
      Additionally, 153 uterine leiomyomas from 46 unselected individuals were
      subjected to and informative in loss of heterozygosity analysis at the FH locus,
      and the five (3.3%) tumors displaying loss of heterozygosity were subjected to FH
      mutation analysis. Although mutation search in the 299 malignant tumors was
      negative, somatic FH mutations were found in two nonsyndromic leiomyomas; a
      splice site change IVS4 + 3A>G, leading to deletion of exon four, and a missense
      mutation Ala196Thr. The occurrence of somatic mutations strongly suggests that FH
      is a true target of the 1q43 deletions. Although uterine leiomyomas are the most
      common tumors of women, specific inactivating somatic mutations contributing to
      the formation of nonsyndromic leiomyomas have not been reported previously.
      Taking into account the apparent risk of uterine leiomyosarcoma associated with
      FH germline mutations, the finding raises the possibility that also some
      nonsyndromic leiomyomas may have a genetic profile that is more prone to
      malignant degeneration. Our data also indicate that somatic FH mutations appear
      to be limited to tumor types observed in hereditary leiomyomatosis and renal cell
      cancer.

PMID- 14695315
TI  - Whole genome amplification of DNA from laser capture-microdissected tissue for
      high-throughput single nucleotide polymorphism and short tandem repeat
      genotyping.
AB  - Genome-wide screening of genetic alterations between normal and cancer cells, as
      well as among subgroups of tumors, is important for establishing molecular
      mechanism and classification of cancer. Gene silencing through loss of
      heterozygosity is widely observed in cancer cells and detectable by analyzing
      allelic loss of single nucleotide polymorphism and/or short tandem repeat
      markers. To use minute quantities of DNA that are available through laser capture
      microdissection (LCM) of cancer cells, a whole genome amplification method that
      maintains locus and allele balance is essential. We have successfully used a o29
      polymerase-based isothermal whole genome amplification method to amplify LCM DNA
      using a proteinase K lysis procedure coupled with a pooling strategy. Through
      single nucleotide polymorphism and short tandem repeat genotype analysis we
      demonstrate that using pooled DNA from two or three separate amplification
      reactions significantly reduces any allele bias introduced during amplification.
      This strategy is especially effective when using small quantities of source DNA.
      Although a convenient alkaline lysis DNA extraction procedure provided
      satisfactory results from using 1500 to 3000 LCM cells, proteinase K digestion
      was superior for lower cell numbers. Accurate genotyping is achieved with as few
      as 100 cells when both proteinase K extraction and pooling are applied.

PMID- 14695316
TI  - Measurement of gene expression in archival paraffin-embedded tissues: development
      and performance of a 92-gene reverse transcriptase-polymerase chain reaction
      assay.
AB  - Throughout the last decade many laboratories have shown that mRNA levels in
      formalin-fixed and paraffin-embedded (FPE) tissue specimens can be quantified by
      reverse transcriptase-polymerase chain reaction (RT-PCR) techniques despite the
      extensive RNA fragmentation that occurs in tissues so preserved. We have
      developed RT-PCR methods that are sensitive, precise, and that have multianalyte
      capability for potential wide use in clinical research and diagnostic assays.
      Here it is shown that the extent of fragmentation of extracted FPE tissue RNA
      significantly increases with archive storage time. Probe and primer sets for RT
      PCR assays based on amplicons that are both short and homogeneous in length
      enable effective reference gene-based data normalization for cross comparison of
      specimens that differ substantially in age. A 48-gene assay used to compare gene
      expression profiles from the same breast cancer tissue that had been either
      frozen or FPE showed very similar profiles after reference gene-based
      normalization. A 92-gene assay, using RNA extracted from three 10- micro m FPE
      sections of archival breast cancer specimens (dating from 1985 to 2001) yielded
      analyzable data for these genes in all 62 tested specimens. The results were
      substantially concordant when estrogen receptor, progesterone receptor, and HER2
      receptor status determined by RT-PCR was compared with immunohistochemistry
      assays for these receptors. Furthermore, the results highlight the advantages of
      RT-PCR over immunohistochemistry with respect to quantitation and dynamic range.
      These findings support the development of RT-PCR analysis of FPE tissue RNA as a
      platform for multianalyte clinical diagnostic tests.

PMID- 14695317
TI  - Improved analysis of the vascular response to arterial ligation using a
      multivariate approach.
AB  - Ligation of the murine common carotid artery induces a reproducible remodeling
      response. The contribution of individual genes can be determined by comparison of
      the phenotypes of genetically modified mice. Although studies have shown the
      response to carotid artery ligation is influenced by many factors, individual
      analyses typically only consider a single factor, the presence of a gene of
      interest. Because of this limitation, measurements of the response to ligation
      show large variation, making the determination of significant difference between
      test groups difficult. In this study, we examine the hypothesis that the
      variation in the response to ligation is due to non-genetic factors in addition
      to genetic factors. Distance from the ligature, a variable common to all arterial
      ligation experiments, is an important source of variation and a significant
      predictor of the remodeling response. We find that the use of statistical
      regression is an improved analysis technique, as it allows the simultaneous
      consideration of multiple variables. We demonstrate this by showing improved
      sensitivity and novel findings in the analysis of the remodeling response in mice
      genetically mutant for the osteopontin gene. We conclude regression analysis
      provides a simple way to improve both comparative power and description of
      vascular remodeling.

PMID- 14695318
TI  - Toll-like receptor 2-deficient mice succumb to Mycobacterium tuberculosis
      infection.
AB  - Recognition of Mycobacterium tuberculosis by the innate immune system is
      essential in the development of an adaptive immune response. Mycobacterial cell
      wall components activate macrophages through Toll-like receptor (TLR) 2,
      suggesting that this innate immune receptor plays a role in the host response to
      M. tuberculosis infection. After aerosol infection with either 100 or 500 live
      mycobacteria, TLR2-deficient mice display reduced bacterial clearance, a
      defective granulomatous response, and develop chronic pneumonia. Analysis of
      pulmonary immune responses in TLR2-deficient mice after 500 mycobacterial aerosol
      challenge showed increased levels of interferon-gamma, tumor necrosis factor
      alpha, and interleukin-12p40 as well as increased numbers of CD4(+) and CD8(+)
      cells. Furthermore, TLR2-deficient mice mounted elevated Ag-specific type 1 T
      cell responses that were not protective because all deficient mice succumb to
      infection within 5 months. Taken together, the data suggests that TLR2 may
      function as a regulator of inflammation, and in its absence an exaggerated immune
      inflammatory response develops.

PMID- 14695319
TI  - Role of ubiquitin carboxy terminal hydrolase-L1 in neural cell apoptosis induced
      by ischemic retinal injury in vivo.
AB  - Ubiquitin is thought to be a stress protein that plays an important role in
      protecting cells under stress conditions; however, its precise role is unclear.
      Ubiquitin expression level is controlled by the balance of ubiquitinating and
      deubiquitinating enzymes. To investigate the function of deubiquitinating enzymes
      on ischemia-induced neural cell apoptosis in vivo, we analyzed gracile axonal
      dystrophy (gad) mice with an exon deletion for ubiquitin carboxy terminal
      hydrolase-L1 (UCH-L1), a neuron-specific deubiquitinating enzyme. In wild-type
      mouse retina, light stimuli and ischemic retinal injury induced strong ubiquitin
      expression in the inner retina, and its expression pattern was similar to that of
      UCH-L1. On the other hand, gad mice showed reduced ubiquitin induction after
      light stimuli and ischemia, whereas expression levels of antiapoptotic (Bcl-2 and
      XIAP) and prosurvival (brain-derived neurotrophic factor) proteins that are
      normally degraded by an ubiquitin-proteasome pathway were significantly higher.
      Consistently, ischemia-induced caspase activity and neural cell apoptosis were
      suppressed approximately 70% in gad mice. These results demonstrate that UCH-L1
      is involved in ubiquitin expression after stress stimuli, but excessive ubiquitin
      induction following ischemic injury may rather lead to neural cell apoptosis in
      vivo.

PMID- 14695320
TI  - Antigen transport into Peyer's patches: increased uptake by constant numbers of M
      cells.
AB  - Membranous (M) cells are specialized epithelial cells of the Peyer's patches that
      sample antigens from the gut lumen, thereby enabling the host to respond
      immunologically. Recent studies suggest that this transport can be up-regulated
      within hours by de novo formation of M cells from enterocytes. To test this
      hypothesis, we used an in vivo model and induced the transcytosis of tracers in
      Peyer's patches by application of Streptococcus pneumoniae R36a into the gut
      lumen. Using cell-type-specific markers, we quantified M cells in the Peyer's
      patch domes, lymphocytes associated with M cells, and the transport rate for
      experimentally applied microbeads after 3 hours of exposure to R36a. The
      transport of latex microbeads was significantly increased by +131% in the R36a
      treated patches as compared to buffer controls (P < 0.001). While in controls,
      each M cell was associated with 2.05 +/- 0.64 lymphocytes, a significant increase
      (+55.1%; P < 0.001) was determined in the R36a-treated patches. However, no
      statistical difference was detected in the percentage of M cells in the dome
      epithelia (46.0 +/- 4.6% versus 45.5 +/- 3.8%). It is concluded that bacteria
      induced up-regulation of particle transport in Peyer's patch domes is due to an
      increased transport rate of the M cells, but not to a de novo formation of M
      cells. The data support the hypothesis that M cells represent a separate cell
      lineage that does not derive from enterocytes on the domes.

PMID- 14695321
TI  - Annexin A1 down-regulation in head and neck cancer is associated with epithelial
      differentiation status.
AB  - Annexin A1 (ANXA1) protein expression was evaluated by Western blot in a series
      of 32 head and neck squamous cell carcinomas (HNSCCs) in a search for molecular
      alterations that could serve as useful diagnostic/prognostic markers. ANXA1 down
      regulation was observed in 24 cases (75%) compared with patient-matched normal
      epithelium. In relation to clinicopathological variables, ANXA1 down-regulation
      was significantly associated with advanced T stages (P = 0.029), locoregional
      lymph node metastases (P = 0.038), advanced disease stage (P = 0.006),
      hypopharyngeal localization (P = 0.038), and poor histological differentiation (P
      = 0.005). ANXA1 expression was also analyzed by immunohistochemistry in paraffin
      embedded sections from 22 of 32 HNSCCs and 8 premalignant lesions. All dysplastic
      tissues showed significantly reduced ANXA1 expression compared to a strong
      positive signal observed in adjacent normal epithelia (except basal and
      suprabasal cells). A close association was observed between ANXA1 expression and
      the histological grade in HNSCC. Well-differentiated tumors presented a positive
      ANXA1 signal in highly keratinized areas whereas moderately and poorly
      differentiated tumors exhibited very weak or negative staining. Our findings
      clearly identify ANXA1 as an effective differentiation marker for the
      histopathological grading of HNSCCs and for the detection of epithelial
      dysplasia.

PMID- 14695322
TI  - Early adaptive responses of the vascular wall during venous arterialization in
      mice.
AB  - Venous arterialization occurs when a vein segment is transposed as a bypass graft
      into the arterial circulation, resulting in a structural and functional
      reorganization of the vascular wall in response to the new local biomechanical
      environment. Although the anatomical changes of venous arterialization have been
      well characterized, the molecular mechanisms of vascular remodeling remain
      incompletely understood. Here, we present a novel model of venous arterialization
      in mice wherein the external jugular vein is connected to the common carotid
      artery. The hemodynamic characteristics of the arterialized vein, as assessed by
      ultrasound and magnetic resonance imaging, resemble features of the arterial
      circulation. Temporal analyses of the morphological changes in the venous segment
      at 1, 3, and 7 days after surgery demonstrate preservation of the endothelium at
      all time points and formation of multiple smooth muscle layers by day 7.
      Expression of endothelial E-selectin and VCAM-1 was documented at early time
      points, concomitant with the presence of neutrophils and monocytes/macrophages in
      the vascular wall. In addition, endothelium-dependent permeability was decreased
      in the arterialized vein when compared to the contralateral control vein. Thus,
      this novel mouse model of venous arterialization displays anatomical and cellular
      features present in other species, and should help to characterize the molecular
      mechanisms of this adaptive response of the vascular wall to changes in its
      biomechanical environment.

PMID- 14695323
TI  - K-ras gene mutation enhances motility of immortalized airway cells and lung
      adenocarcinoma cells via Akt activation: possible contribution to non-invasive
      expansion of lung adenocarcinoma.
AB  - Point mutations of the K-ras gene, which are found in 10 to 30% of lung
      adenocarcinomas, are regarded as being an early event during the carcinogenesis.
      Autonomous vigorous motility of neoplastic cells, as well as growth and survival
      advantages, are considered to be necessary for cancer development and
      progression. The present study describes the contributions of the K-ras gene
      mutation and its downstream pathway via phosphatidylinositol 3-OH kinase (PI3K)
      Akt to the cell motility in an immortalized human peripheral airway epithelial
      cell (HPL1D) and lung adenocarcinoma cells (A549, H820, TKB6, and TKB14). We have
      also evaluated the relationship between pathological events and the K-ras-Akt
      pathway using surgically resected lung tumors. The HPL1D cells transfected with
      the mutated K-ras gene (HPL-V12) showed a significant increase in cell motility
      compared to those transfected with empty vector (HPL-E) or wild-type K-ras gene
      (HPL-K). The enhanced motility in the HPL-V12 cells was markedly reduced by
      either treatment with inhibitors of ras, PI3K, and/or MEK, or by transfection
      with the dominant-negative mutant Akt (dnAkt). The lung adenocarcinoma cells
      bearing the K-ras gene mutation (A549 and H820) showed consistently higher levels
      of cell motilities than those without the mutation (TKB6 and TKB14), and the
      motility of A549 and H820 cells were significantly inhibited by dnAkt
      transfection. These results suggest that the K-ras gene mutation could enhance
      the motility of neoplastic cells through a pathway involving PI3K-Akt. Actually,
      among the surgically resected lung tumors, the adenocarcinomas with the K-ras
      gene mutation tended to show a higher frequency and intensity of immunoreactivity
      for phosphorylated Akt (p-ser473Akt) than those without the mutation, supporting
      the in vitro observation that the mutated K-ras can activate the PI3K-Akt
      pathway. Immunoreactivity for p-ser473Akt was also seen in the pre-malignant and
      early lesions at a frequency similar to that in the advanced lung
      adenocarcinomas,. No correlation was seen between p-ser473Akt immunoreactivity
      and lymphatic/organ metastasis or prognosis. These results taken together suggest
      that the K-ras-Akt pathway might facilitate the motility of neoplastic cells
      during the early period of carcinogenesis in lung adenocarcinomas, and may
      contribute to their non-invasive expansion along the alveolar septa, rather than
      invasion or metastasis.

PMID- 14695324
TI  - Chronic exposure to the carcinogenic compound benzo[a]pyrene induces larger and
      phenotypically different atherosclerotic plaques in ApoE-knockout mice.
AB  - Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon with atherogenic and
      carcinogenic properties. The role of B[a]P in carcinogenesis is well established,
      and thought to exert via enzymatic activation into reactive metabolites that are
      capable of binding to the DNA leading to uncontrolled proliferation. However, the
      mechanism underlying the atherogenic properties of B[a]P is still unclear.
      Therefore, the effects of chronic B[a]P exposure on atherosclerotic plaque
      development in apolipoprotein E knockout (apoE-KO) mice were studied. ApoE-KO
      mice were orally treated with 5 mg/kg/bw B[a]P once per week for 12 or 24
      consecutive weeks. Levels of reactive B[a]P metabolites in the arterial tree
      (from the aortic arch until the iliac artery bifurcations) were high as shown by
      the level of B[a]P DNA-binding products measured in DNA isolated from the entire
      aorta (38.9 +/- 4.8 adducts/10(8) nucleotides). Analysis of atherosclerotic
      lesions in the aortic arch showed no influence of B[a]P on location or number of
      lesions. Moreover, no increased levels of p53 nuclear protein accumulation or
      cell proliferation, as detected by immunohistochemistry, were seen in the plaques
      of the B[a]P-exposed animals. However, the effects of B[a]P on advanced lesions
      were obvious: advanced plaques were larger and more prone to lipid core
      development and plaque layering at both 12 and 24 weeks (P < 0.05). In the B[a]P
      exposed animals advanced plaques contained more T-lymphocytes and macrophages
      than in the control animals at both end points (P < 0.05). These data suggest
      that B[a]P does not initiate atherosclerosis in apoE-KO mice, but accelerates the
      progression of atherosclerotic plaques via a local inflammatory response.

PMID- 14695325
TI  - Reduction in arthritis severity and modulation of immune function in tissue
      factor cytoplasmic domain mutant mice.
AB  - Tissue factor (TF), a transmembrane receptor for plasma factor VII(a), is the
      main initiator of the coagulation cascade. It has also been implicated in
      noncoagulant processes, including inflammation. The function of the TF
      cytoplasmic domain was studied in mice in which 18 of the 20 cytoplasmic amino
      acids were deleted. This mutation (TF(deltaCT/deltaCT)) is not associated with
      alterations in blood coagulation. Arthritis was induced by intra-articular
      injection of methylated bovine serum albumin (mBSA) in mice preimmunized with
      mBSA. Arthritis severity was significantly reduced in TF(deltaCT/deltaCT) mice
      compared to wild-type mice, including reductions in synovitis, synovial exudate,
      cartilage degradation, and bone damage. A marked reduction in synovial
      interleukin (IL)-1beta and IL-6 mRNA was also observed. Serum anti-mBSA IgG1, but
      not IgG2a, was increased in mutant mice. Cutaneous delayed-type hypersensitivity
      and antigen-induced T-cell proliferation were reduced in TF(deltaCT/deltaCT)
      compared to wild-type mice. A significant down-regulation of lipopolysaccharide
      induced IL-1, tumor necrosis factor, IL-6, macrophage migration inhibitory
      factor, and matrix metalloproteinase-13 mRNA was observed in immunized, but not
      in naive TF(deltaCT/deltaCT) macrophages ex vivo. These data suggest a
      significant role for the cytoplasmic domain of TF in the regulation of the
      immunoinflammatory responses, a murine arthritis model, and macrophage function.

PMID- 14695326
TI  - Retrovirally mediated overexpression of versican v3 reverses impaired
      elastogenesis and heightened proliferation exhibited by fibroblasts from Costello
      syndrome and Hurler disease patients.
AB  - The phenotypic resemblance of patients with Costello syndrome and Hurler disease
      has been linked to impaired formation of elastic fibers that coincides with
      elevated cellular proliferation. Impaired elastogenesis in these diseases
      associates with respective abnormal accumulation of chondroitin sulfate and
      dermatan sulfate proteoglycans that induce cell surface shedding of elastin
      binding protein (EBP) normally required for intracellular chaperoning of
      tropoelastin and its assembly into elastic fibers. A variant of the chondroitin
      sulfate proteoglycan versican, V3, which lacks chondroitin sulfate, has recently
      been shown to stimulate elastic fiber assembly and decrease proliferation when
      expressed by retroviral transduction in arterial smooth muscle cells. However,
      the mechanism(s) by which V3 influences this phenotype is not known. We now
      demonstrate that transduction of skin fibroblasts from Costello syndrome and
      Hurler disease patients with cDNA to versican V3 completely reverses impaired
      elastogenesis and restores normal proliferation of these cells. This phenotypic
      reversal is accompanied by loss of chondroitin sulfate from the cell surface and
      increased levels of EBP. Versican V3 transduction of skin fibroblasts from GM(1)
      gangliosidosis patients, which lack EBP, failed to restore impaired
      elastogenesis. These results suggest that induction of elastic fiber production
      by gene transfer of versican V3 in skin fibroblasts is mediated by rescue of the
      tropoelastin chaperone, EBP.

PMID- 14695327
TI  - Independent pathways of P-selectin and complement-mediated renal
      ischemia/reperfusion injury.
AB  - Evidence from in vitro studies indicates that complement activation regulates the
      expression of P-selectin on endothelial cells. This suggests that in disorders
      such as ischemia/reperfusion injury, in which both complement and P-selectin have
      been shown to play a role, complement activation is a primary event and the
      effects of P-selectin are secondary. To test this hypothesis in vivo, we examined
      a mouse kidney model of ischemia/reperfusion injury. Surprisingly, the time
      course and extent of expression of P-selectin was unaltered in C3-deficient mice
      compared with wild-type mice, in which there was rapid but transient up
      regulation of P-selectin on capillary walls and slower accumulation of complement
      split product on the tubular epithelium. In addition, treatment with anti-P
      selectin antibody to reduce the neutrophil-mediated reperfusion damage was
      equally effective in the absence of C3. These data imply that complement and P
      selectin-mediated pathways of renal reperfusion injury are mutually independent,
      a conclusion that is possibly explained by the differences in the location and
      time kinetics of complement activation and P-selectin expression. We conclude
      that in vivo interaction between complement and P-selectin is limited because of
      time and spatial considerations. Consequently, complement and P-selectin pose
      distinct targets for therapy.

PMID- 14695328
TI  - Peripheral tissue involvement in sporadic, iatrogenic, and variant Creutzfeldt
      Jakob disease: an immunohistochemical, quantitative, and biochemical study.
AB  - Human prion diseases are rare fatal neurodegenerative conditions that occur as
      acquired, familial, or idiopathic disorders. A key event in their pathogenesis is
      the accumulation of an altered form of the prion protein, termed PrP(Sc), in the
      central nervous system. A novel acquired human prion disease, variant Creutzfeldt
      Jakob disease, is thought to result from oral exposure to the bovine spongiform
      encephalopathy agent. This disease differs from other human prion diseases in its
      neurological, neuropathological, and biochemical phenotype. We have used
      immunohistochemistry and Western blot techniques to analyze the tissue
      distribution and biochemical properties of PrP(Sc) in peripheral tissues in a
      unique series of nine cases of variant Creutzfeldt-Jakob disease. We have
      compared this with the distribution and biochemical forms found in all of the
      major subtypes of sporadic Creutzfeldt-Jakob disease and in a case of iatrogenic
      Creutzfeldt-Jakob disease associated with growth hormone therapy. The results
      show that involvement of the lymphoreticular system is a defining feature of
      variant Creutzfeldt-Jakob disease, but that the biochemical isoform of PrP(Sc)
      found is influenced by the cell type in which it accumulates.

PMID- 14695329
TI  - Expression of the small heat-shock protein alphaB-crystallin in tauopathies with
      glial pathology.
AB  - Intracellular accumulations of filamentous material composed of tau proteins are
      defining features of sporadic and familial neurodegenerative disorders termed
      "tauopathies." In Alzheimer's disease, the most common tauopathy, tau pathology
      is predominantly localized within neurons; however, robust glial pathology occurs
      in other tauopathies. Although the pathogenesis of tauopathies remains primarily
      unknown, molecular chaperones such as heat-shock proteins (HSPs) are implicated
      in these tau disorders as well as other neurodegenerative diseases characterized
      by the accumulation of insoluble protein aggregates such as alpha-synuclein in
      Parkinson's disease and polyglutamine in Huntington's disease. We analyzed a
      variety of tauopathies with antibodies to a panel of HSPs to determine their role
      in the pathogenesis of these disorders. Although HSPs are not found in neuronal
      tau inclusions, we demonstrate increased expression of the small HSP alphaB
      crystallin in glial inclusions of both sporadic and familial tauopathies. alphaB
      crystallin was observed in a subset of astrocytic and oligodendrocytic tau
      inclusions as well as the neuropil thread pathology in cellular processes, but
      the co-expression of alphaB-crystallin with tau inclusions was relatively
      specific to tauopathies with extensive glial pathology. Thus, increased alphaB
      crystallin expression in glial tau inclusions may represent a response by glia to
      the accumulation of misfolded or aggregated tau protein that is linked to the
      pathogenesis of the glial pathology and distinct from mechanisms underlying
      neuronal tau pathology in neurodegenerative disease.

PMID- 14695330
TI  - Adult gonadal hormones selectively regulate sexually dimorphic quantitative
      traits observed in experimental allergic encephalomyelitis.
AB  - Experimental allergic encephalomyelitis (EAE) and multiple sclerosis (MS) are
      characterized by strong sexual dimorphisms, many of which may be due to
      genetically controlled sex hormone effects on the immune system, the central
      nervous system (CNS), or both. In the present study we used 487 gonadectomized
      and 376 intact age-matched F(2) mice generated through crosses of B10.S/SgMcdJ
      and SJL/J mice to assess the role of adult gonadal hormones in regulating
      clinical and histopathological quantitative traits (QT) associated with EAE in
      the context of genetic heterogeneity. We found that gonadectomy resulted in
      different effects, depending on the QT and the sex of the mouse. Ovariectomized
      mice on average had lower cumulative clinical disease scores, shorter duration of
      clinical signs, and increased peak disease scores. This trend was accompanied by
      a significant increase in the incidence of acute, progressive EAE which is more
      frequently seen in intact and orchiectomized males. Although spinal cord (SC)
      inflammation was the better predictor of clinical signs of EAE in both sexes,
      ovariectomized females had considerable reductions in nearly all
      histopathological QT in both the brain and SC. Orchiectomy resulted in modestly
      significant increases in disease severity and peak score and earlier onset of
      clinical signs. With the exception of SC demyelination and lesion scores,
      orchiectomy had no effect on histopathological QT. Importantly, gonadectomy
      reduced but did not completely abolish any of the sexually dimorphic clinical QT
      seen in intact mice. It did however, lead to a significant sexual dimorphism in
      incidence and severity not seen in intact mice. For histopathological QT, no
      sexual dimorphism was detected for brain lesions in either intact or
      gonadectomized mice. In contrast, SC histopathological QT exhibited significant
      sexual dimorphisms, which were impacted by gonadectomy. The results from this
      study indicate that within the context of genetic heterogeneity, circulating
      gonadal hormones influence both clinical and histopathological QT in this model
      of MS, but they do not solely account for the sexual dimorphisms seen in these
      traits. Thus, additional mechanisms must play a role in regulating gender
      differences in autoimmune disease of the CNS.

PMID- 14695331
TI  - Expression and activation of mitogen-activated protein kinase kinases-3 and -6 in
      rheumatoid arthritis.
AB  - The p38 mitogen-activated protein (MAP) kinase signal transduction pathway
      regulates the production of interleukin-1 and tumor necrosis factor-alpha. p38
      kinase inhibitors are effective in animal models of arthritis and are currently
      being developed in rheumatoid arthritis (RA). However, little is known about the
      upstream kinases that control the activation of p38 in RA synovium. In vitro
      studies previously identified the MAP kinase kinases (MAPKKs) MKK3 and MKK6 as
      the primary regulators of p38 phosphorylation and activation. To investigate a
      potential role for MKK3 and MKK6 in RA, we evaluated their expression and
      regulation in RA synovium and cultured fibroblast-like synoviocytes (FLS).
      Immunohistochemistry demonstrated that MKK3 and MKK6 are expressed in RA and
      osteoarthritis (OA) synovium. Digital image analysis showed no significant
      differences between OA and RA with regard to expression or distribution. However,
      phosphorylated MKK3/6 expression was significantly higher in RA synovium and was
      localized to the sublining mononuclear cells and the intimal lining. Actin
      normalized Western blot analysis of synovial tissue lysates confirmed the
      increased expression of phosphorylated MKK3/6 in RA. Western blot analysis
      demonstrated constitutive expression of MKK3 and MKK6 in RA and OA FLS. Phospho
      MKK3 levels were low in medium-treated FLS, but were rapidly increased by
      interleukin-1 and tumor necrosis factor-alpha, although phospho-MKK6 levels only
      modestly increased. p38 co-immunoprecipitated with MKK3 and MKK6 from cytokine
      stimulated FLS and the complex phosphorylated activating transcription factor-2
      in an in vitro kinase assay. These data are the first documentation of MKK3 and
      MKK6 activation in human inflammatory disease. By forming a complex with p38 in
      synovial tissue and FLS, these kinases can potentially be targeted to regulate
      the production of proinflammatory cytokine production in inflamed synovium.

PMID- 14695332
TI  - Mechanical overload induces VEGF in cartilage discs via hypoxia-inducible factor.
AB  - VEGF (vascular endothelial growth factor) is not only one of the most important
      angiogenesis factors, but is involved also in inflammatory processes. Recent
      studies have shown that VEGF as well as its receptor VEGFR-2 are expressed on
      osteoarthritic chondrocytes, but not on normal adult chondrocytes. Since
      mechanical overload is one of the causative factors for osteoarthritis, we
      studied its effect on VEGF expression on bovine cartilage disks that were
      compressed once with a strain of 50% and a strain rate of 1/second. Under these
      conditions, control disks (without pressure) were completely negative for VEGF
      expression as evidenced by immunocytochemical stainings as well as by enzyme
      linked immunosorbent assay (ELISA) measurements. In contrast, 4 days after
      mechanical overload, the cartilage disks were positive in both detection methods.
      In addition, after mechanical overload chondrocytes were strongly immunopositive
      for hypoxia-inducible factor-1alpha (HIF-1alpha), the limiting protein of the
      dimeric transcription factor HIF-1 that is known to induce VEGF expression.
      Furthermore, the matrix metalloproteases MMP-1, MMP-3, and MMP-13, could be
      easily detected in pressure-treated disks by immunohistochemistry whereas
      staining in controls was low or undetectable. The tissue inhibitors of
      metalloproteinases (TIMP-1 and -2) could be detected in controls but not in
      samples treated with mechanical overload. To prove that increased MMP or
      decreased TIMP expression could be a result of the autocrine action of VEGF on
      chondrocytes, we repeated the experiments in the presence of a specific inhibitor
      for the kinase activity of the VEGFR-2. This inhibitor was effective to reduce
      mechanically induced MMP-1, -3, and -13 immunostaining and to restore TIMP
      expression. Taking together, these findings indicate that VEGF is induced in
      chondrocytes by mechanical overload and mediates destructive processes in
      osteoarthritis as an autocrine factor.

PMID- 14695333
TI  - Progression in cutaneous malignant melanoma is associated with distinct
      expression profiles: a tissue microarray-based study.
AB  - Cutaneous malignant melanoma remains the leading cause of skin cancer death in
      industrialized countries. Clinical and histological variables that predict
      survival, such as Breslow's index, tumor size, ulceration, or vascular invasion
      have been identified in malignant melanoma. Nevertheless, the potential relevance
      of biological variables still awaits an in-depth exploration. Using tissue
      microarrays (TMAs), we retrospectively analyzed 165 malignant melanoma samples
      from 88 patients corresponding to distinct histological progression phases,
      radial, vertical, and metastases. A panel of 39 different antibodies for cell
      cycle, apoptosis, melanoma antigens, transcription factors, DNA mismatch repair,
      and other proteins was used. Integrating the information, the study has
      identified expression profiles distinguishing specific melanoma progression
      stages. Most of the detected alterations were linked to the control of cell cycle
      G1/S transition; cyclin D1 was expressed in radial cases 48% (12 of 25) with
      significant lost of expression in vertical cases 14% (9 of 65), P = 0.002;
      whereas p16(INK4a) (89% in vertical versus 71% in metastatic cases, P = 0.009)
      and p27(KIP1) (76% in radial versus 45% in vertical cases, P = 0.010) were
      diminished in advanced stages. The study also defines a combination of biological
      markers associated with shorter overall survival in patients with vertical growth
      phase melanoma, that provided a predictor model with four antibodies (Ki67,
      p16(INK4a), p21(CIP1), and Bcl-6). This predictor model was validated using an
      independent series of 72 vertical growth phase melanoma patients.

PMID- 14695334
TI  - Increased expression of a Myc target gene Mina53 in human colon cancer.
AB  - Mina53 is a novel Myc target gene that we previously demonstrated to be involved
      in cell proliferation. We studied, here, the expression of Mina53 in colon cancer
      to examine its possible role in carcinogenesis. We generated a specific
      monoclonal anti-human Mina53 antibody and found that colon tumor cell lines
      expressed Mina53 highly. We also found that expression of Mina53 was elevated in
      colon tumor tissues by immunoblotting analysis. Tissue sections of 23 surgical
      cases of adenocarcinoma and 1 case of adenoma were stained immunohistochemically,
      and the expression of Mina53 was found to be elevated in all of the
      adenocarcinomas compared to adjacent nonneoplastic tissues, which showed little
      staining. Deeply invading tumors as well as tumors that have invaded lymphatic
      vessels showed strong immunoreactivity against anti-Mina53 antibody. Mina53 was
      expressed in all pathological grades of cancer as well as in the adenoma.
      Staining patterns of Ki-67, a biomarker for cell proliferation, were similar to
      those of Mina53 in most cases, but the percentage of tumor cells stained by anti
      Mina53 was higher. Although anti-Ki-67 antibody strongly stained some well
      proliferating nonneoplastic cells including cells in the deeper part of the
      crypts and in lymphoid germinal centers, antibody to Mina53 rarely stained those
      cells. Suppression of mina53 expression severely suppressed proliferation of
      colon tumor cells in vitro. Together, our results indicate that the elevated
      expression of Mina53 is a characteristic feature in colon cancer, one that may
      have therapeutic applications.

PMID- 14695335
TI  - Gene expression analysis of human prostate carcinoma during hormonal therapy
      identifies androgen-responsive genes and mechanisms of therapy resistance.
AB  - The androgen-signaling pathway is critical to the development and progression of
      prostate cancer and androgen ablation is a mainstay of therapy for this disease.
      We performed a genome-wide expression analysis of human prostate cancer during
      androgen ablation therapy to identify genes regulated by androgen and genes
      differentially expressed after the development of resistance. Six hundred and
      fifty-four of 63,175 probe sets detected significant expression changes after 3
      months of treatment with goserelin and flutamide. This included 149 genes that
      were also differentially expressed 36 hours after androgen withdrawal in LNCaP
      cells. These genes reflect the physiological changes that occur in treated tumors
      and include potential direct targets of the androgen receptor. Expression
      profiles of androgen ablation-resistant tumors demonstrated that many of the gene
      expression changes detected during therapy were no longer present suggesting a
      reactivation of the androgen response pathway in the absence of exogenous
      hormone. Therapy resistance was associated with differential expression of a
      unique set of genes that reflect potential mechanisms of reactivation.
      Specifically an up-regulation of the androgen receptor and key enzymes for
      steroid biosynthesis suggest that resistant tumors have increased sensitivity to
      and endogenous synthesis of androgenic hormones. The specific pathways of
      reactivation provide opportunities for classification of resistant tumors and
      targeted therapies.

PMID- 14695336
TI  - Increased expression of beta6-integrin in skin leads to spontaneous development
      of chronic wounds.
AB  - Integrin alphavbeta6 is an epithelial cell-specific receptor that is not normally
      expressed by resting epithelium but its expression is induced during wound
      healing. The function of alphavbeta6-integrin in wound repair is not clear. In
      the present study, we showed that beta6-integrin expression was strongly up
      regulated in the epidermis in human chronic wounds but not in different forms of
      skin fibrosis. To test whether increased beta6-integrin expression plays a role
      in abnormal wound healing we developed four homozygous transgenic mouse lines
      that constitutively expressed human beta6-integrin in the epithelium. The mice
      developed normally and did not show any histological abnormalities in the skin.
      The rate of experimental skin wound closure was unaltered and the wounds healed
      without significant scar formation. However, during breeding program 16.1 to
      27.0% of transgenic mice developed spontaneous, progressing fibrotic chronic
      ulcers. None of the wild-type animals developed these lesions. The chronic
      lesions had areas with severe fibrosis and numerous activated macrophages and
      fibroblasts expressing transforming growth factor (TGF)-beta. The level of TGF
      beta1 was significantly increased in the lesions as compared with normal skin.
      The findings suggest that increased alphavbeta6-integrin in keratinocytes plays
      an active part in abnormal wound healing possibly through a mechanism involving
      increased activation of TGF-beta.

PMID- 14695337
TI  - Increased expression of elastolytic cysteine proteases, cathepsins S and K, in
      the neointima of balloon-injured rat carotid arteries.
AB  - The matrix-degrading activity of several proteases are involved in the
      accelerated breakdown of extracellular matrix associated with vascular remodeling
      during the development of atherosclerosis and vascular injury-induced neointimal
      formation. Previous studies have shown that the potent elastolytic cysteine
      proteases, cathepsins S and K, are overexpressed in atherosclerotic lesions in
      human and animal models. However, the role of these cathepsins in vascular
      remodeling remains unclear. In the present study, the expressions of cathepsin S
      and K and their inhibitor cystatin C were examined during arterial remodeling
      using a rat carotid artery balloon-injury model. The increase in both cathepsin S
      and K mRNA levels was observed from day 1 and day 3 through day 14 following the
      induction of balloon injury, respectively. Western blotting analysis revealed
      that both cathepsin S and K protein levels also increased in the carotid arteries
      during neointima formation, coinciding with an increase elastolytic activity
      assayed using Elastin-Congo red, whereas, no significant change in the
      expressions of cystatin C mRNA and protein was observed during follow-up periods
      after injury. Immunohistochemistry, Western blot, and in situ hybridization
      showed that the increase of cathepins S and K and the decrease of cystatin C
      occurred preferentially in the developing neointima. These findings suggest that
      cathepsin S and K may participate in the pathological arterial remodeling
      associated with restenosis.

PMID- 14695338
TI  - S100A4/Mts1 produces murine pulmonary artery changes resembling plexogenic
      arteriopathy and is increased in human plexogenic arteriopathy.
AB  - S100A4/Mts1 confers a metastatic phenotype in tumor cells and may also be related
      to resistance to apoptosis and angiogenesis. Approximately 5% of transgenic mice
      overexpressing S100A4/Mts1 develop pulmonary arterial changes resembling human
      plexogenic arteriopathy with intimal hyperplasia leading to occlusion of the
      arterial lumen. To assess the pathophysiological significance of this
      observation, immunohistochemistry was applied to quantitatively analyze
      S100A4/Mts1 expression in pulmonary arteries in surgical lung biopsies from
      children with pulmonary hypertension secondary to congenital heart disease.
      S100A4/Mts1 was not detected in pulmonary arteries with low-grade hypertensive
      lesions but was expressed in smooth muscle cells of lesions showing neointimal
      formation and with increased intensity in vessels with an occlusive neointima and
      plexiform lesions. Putative downstream targets of S100A4/Mts1 include Bax, which
      is pro-apoptotic, and the pro-angiogenic vascular endothelial growth factor
      (VEGF). The increase in S100A4/Mts1 expression precedes heightened expression of
      Bax in progressively severe neointimal lesions but in non-S100A4/Mts1-expressing
      cells. VEGF immunoreactivity did not correlate with severity of disease. The
      relationship of increased S100A4/Mts1 to pathologically similar lesions in the
      transgenic mice and patients occurs despite differences in localization
      (endothelial versus smooth muscle cells).

PMID- 14695339
TI  - Activation of peroxisome proliferator-activated receptor-gamma in dendritic cells
      inhibits the development of eosinophilic airway inflammation in a mouse model of
      asthma.
AB  - Peroxisome proliferator-activated receptors (PPARs) are activated by an array of
      polyunsaturated fatty acid derivatives, oxidized fatty acids, and phospholipids
      and are proposed to be important modulators of immune and inflammatory responses.
      Recently, we showed that activation of PPAR-gamma alters the maturation process
      of dendritic cells (DCs), the most potent antigen-presenting cells. In the
      present report, we investigated the possibility that, by targeting DCs, PPAR
      gamma activation may be involved in the regulation of the pulmonary immune
      response to allergens. Using a model of sensitization, based on the intratracheal
      transfer of ovalbumin (OVA)-pulsed DCs, we show that rosiglitazone, a selective
      PPAR-gamma agonist, reduces the proliferation of Ag-specific T cells in the
      draining mediastinal lymph nodes but, surprisingly enough, dramatically increases
      the production of the immunoregulatory cytokine interleukin (IL)-10 by T cells,
      as compared to control mice sensitized with OVA-pulsed DCs. After aerosol
      challenge, the recruitment of eosinophils in the bronchoalveolar lavage fluids
      was strongly reduced compared to control mice. Finally, T cells from the
      mediastinal lymph nodes produced higher amounts of IL-10 and interferon-gamma.
      Inhibition of IL-10 activity with anti-IL-10R antibodies partly restored the
      inflammation. The specificity of the phenomenon was confirmed by treating OVA
      pulsed DCs with ciglitazone, another PPAR-gamma agonist, and by using GW9662, a
      PPAR-gamma antagonist. Our data suggest that PPAR-gamma activation prevents
      induction of Th2-dependent eosinophilic airway inflammation and might contribute
      to immune homeostasis in the lung.

PMID- 14695340
TI  - pp32 reduction induces differentiation of TSU-Pr1 cells.
AB  - pp32 (ANP32A) is a nuclear phosphoprotein expressed as a nonmutated form in self
      renewing cell populations and neoplastic cells. Mechanistically, pp32 may
      regulate pathways important in the process of differentiation as part of separate
      complexes inhibiting histone acetylation and regulating immediate-early and
      cytokine mRNA stability. Prostatic adenocarcinomas express pp32 in a
      differentiation related manner-well-differentiated tumors express lower levels of
      pp32 than poorly differentiated tumors. In benign prostate, pp32 is expressed in
      basal cells but not in terminally differentiated glandular cells. Based on these
      observations, we hypothesized that reduction of pp32 expression might be an
      important differentiation signal. We used anti-sense pp32 and RNAi transfection
      to study the effects of reduced pp32 expression in the TSU-Pr1 carcinoma cell
      line. pp32 reduction induced TSU-Pr1 cells to differentiate into neuronal-like
      cells with associated inhibition of growth. Reduction of pp32 and consequent
      differentiation were accompanied by a marked reduction in expression of SET,
      which complexes with pp32, by a marked change in acetylation status of histone
      H4, and by further differential expression of genes in differentiation pathways.
      Thus, reduction of pp32 in the undifferentiated TSU-Pr1 neoplastic cell line
      induces differentiation and thus may be an element of a differentiation control
      pathway in both normal and neoplastic cells.

PMID- 14695341
TI  - Defining a 0.5-mb region of genomic gain on chromosome 6p22 in bladder cancer by
      quantitative-multiplex polymerase chain reaction.
AB  - Metaphase-based comparative genomic hybridization (CGH) has identified recurrent
      regions of gain on different chromosomes in bladder cancer, including 6p22. These
      regions may contain activated oncogenes important in disease progression. Using
      quantitative multiplex polymerase chain reaction (QM-PCR) to study DNA from 59
      bladder tumors, we precisely mapped the focal region of genomic gain on 6p22. The
      marker STS-X64229 had copy number increases in 38 of 59 (64%) tumors and the
      flanking markers, RH122450 and A009N14, had copy number gains in 33 of 59 (56%)
      and 26 of 59 (45%) respectively. Contiguous gain was present for all three
      markers in 14 of 59 (24%) and for two (RH122450 and STS-X64229) in 25 of 59
      (42%). The genomic distance between the markers flanking STS-X64229 is 0.5
      megabases, defining the minimal region of gain on 6p22. Locus-specific interphase
      fluorescence in situ hybridization confirmed the increased copy numbers detected
      by QM-PCR. Current human genomic mapping data indicates that an oncogene, DEK, is
      centrally placed within this minimal region. Our findings demonstrate the power
      of QM-PCR to narrow the regions identified by CGH to facilitate identifying
      specific candidate oncogenes. This also represents the first study identifying
      DNA copy number increases for DEK in bladder cancer.

PMID- 14695342
TI  - Chronic inhaled ovalbumin exposure induces antigen-dependent but not antigen
      specific inhalational tolerance in a murine model of allergic airway disease.
AB  - Sensitized mice acutely challenged with inhaled ovalbumin (OVA) develop allergic
      airway inflammation, characterized by OVA-specific IgE production, airway
      eosinophilia, increased pulmonary B and T lymphocytes, and airway
      hyperreactivity. In this study, a chronic exposure model was developed and two
      distinct patterns of response were observed. Discontinuous inhalational exposure
      to OVA (6 weeks) produced airway inflammation and hyperreactivity that were
      similar to acute (10 days) responses. Continuous inhalational exposure to OVA (6
      or 11 weeks) resulted in attenuation of airway eosinophilia and
      hyperresponsiveness without reduction of OVA-specific IgE and IgG(1) levels. The
      inhibition of airway inflammation was dependent on continuous exposure to
      antigen, because continuously exposed mice with attenuated inflammatory responses
      redeveloped allergic airway disease if the OVA aerosols were interrupted and then
      restarted (11-week-discontinuous). Inhalational tolerance induced by continuous
      OVA exposure demonstrated bystander suppression of cockroach allergen-mediated
      airway eosinophilia. These findings may be attributed to changes in production of
      the anti-inflammatory cytokine interleukin-10 during continuous OVA aerosol
      exposure. The symptomatic and asymptomatic allergic responses in human asthmatics
      could be explained by similar variable or discontinuous exposures to
      aeroantigens.

PMID- 14695343
TI  - KIT mutations are common in testicular seminomas.
AB  - Expression of KIT tyrosine kinase is critical for normal germ cell development
      and is observed in the majority of seminomas. Activating mutations in KIT are
      common in gastrointestinal stromal tumors and mastocytosis. In this study we
      examined the frequency and spectrum of KIT mutations in 54 testicular seminomas,
      1 ovarian dysgerminoma and 37 non-seminomatous germ cell tumors (NSGCT). Fourteen
      seminomas (25.9%) contained exon 17 point mutations including D816V (6 cases),
      D816H (3 cases), Y823D (2 cases), and single examples of Y823C, N822K, and T801I.
      No KIT mutations were found in the ovarian dysgerminoma or the NSGCTs. In
      transient transfection assays, mutant isoforms D816V, D816H, Y823D, and N822K
      were constitutively phosphorylated in the absence of the natural ligand for KIT,
      stem cell factor (SCF). In contrast, activation of T801I and wild-type KIT
      required SCF. Mutants N822K and Y823D were inhibited by imatinib mesylate
      (Gleevec, previously STI571) whereas D816V and D816H were both resistant to
      imatinib mesylate. Biochemical evidence of KIT activation, as assessed by KIT
      phosphorylation and KIT association with phosphatidylinositol (PI) 3-kinase in
      tumor cell lysates, was largely confined to seminomas with a genomic KIT
      mutation. These findings suggest that activating KIT mutations may contribute to
      tumorigenesis in a subset of seminomas, but are not involved in NSGCT.

PMID- 14695344
TI  - Detection of differentially expressed genes in an isogenic breast metastasis
      model using RNA arbitrarily primed-polymerase chain reaction coupled with array
      hybridization (RAP-array).
AB  - To facilitate the study of the mechanisms of breast cancer metastasis we have
      previously characterized a pair of breast tumor cell lines that originate from
      the same breast tumor cell line MDA-MB-435, but which have diametrically opposite
      metastatic capabilities. These cell lines constitute a stable and accessible
      experimental system for the identification of metastasis-related genes and for
      the study of their role in the process of metastasis. In this study, we used a
      combination of RNA arbitrarily primed-polymerase chain reaction (RAP-PCR)
      fingerprinting and cDNA arrays (here termed "RAP-array") to identify genes
      differentially expressed with respect to metastatic phenotype. RAP-PCR was used
      to generate radioactive probes of reduced complexity for hybridization to nylon
      membranes containing 588 cDNAs of known identity. Single RAP-PCR fingerprint
      probes hybridized from 61 (10.4%) to 116 (19.7%) of the filter array targets,
      with a signal detection overlap of approximately 21%. A total of 344 (57%) of the
      588 target genes were detected by five single RAP-PCR fingerprints. The advantage
      of using reduced complexity probes was highlighted by the fact that the
      combination of RAP probes before hybridization compromised the overall detection
      rate by up to 40%. Sequential application of RAP-PCR probes allowed the screening
      of a greater, and an alternative fraction of the transcript population than was
      achieved with a radiolabeled total cDNA probe. Verification by quantitative
      reverse transcriptase-PCR confirmed significantly increased expression of keratin
      9 (>100-fold) in nonmetastatic breast tumor cells and of CD70 (fivefold) in
      metastatic cells. The differential expression of keratin 9 and CD70 was
      maintained between cells grown as primary xenografts in athymic mice. The RAP
      array method enabled the detection of genes not revealed using other screening
      methods and that are candidates for further investigation in the context of
      metastatic phenotype.

PMID- 14695345
TI  - A mouse model of uterine leiomyosarcoma.
AB  - We are using an approach that is based on the cre/loxP recombination process and
      involves a binary system of Cre-producing and Cre-responding transgenic mice to
      achieve ubiquitous or tissue-specific expression of oncoproteins. To develop
      mouse models of tumorigenesis, Cre-producers are mated with responder animals
      carrying a dormant oncogene targeted into the 3' untranslated region of the locus
      encoding cytoplasmic beta-actin (actin cassette). Production of oncoprotein from
      a bicistronic message is accomplished in bitransgenic progeny by Cre-mediated
      excision of a segment flanked by loxP sites that is located upstream from the
      oncogenic sequence. Widespread Cre-dependent activation and expression of an
      actin-cassette transgene encoding the T antigens of the SV40 early region (SVER)
      commencing in embryos was compatible with normal development and did not impair
      viability. However, at approximately 3 months of age, all female animals
      developed massive uterine leiomyosarcomas, whereas practically all males
      exhibited enormously enlarged seminal vesicles because of pronounced hyperplasia
      of the smooth muscle layers. In addition, because of smooth muscle
      hyperproliferation, marked dilation of the gallbladder was observed in mice of
      both sexes. To begin exploring aberrant signaling events in the SVER-triggered
      tumorigenic pathways, we analyzed the expression profile of leiomyosarcomas by
      DNA microarray analysis.

PMID- 14695347
TI  - Rapid neurofibrillary tangle formation after localized gene transfer of mutated
      tau.
AB  - Neurofibrillary pathology was produced in the brains of adult rats after
      localized gene transfer of human tau carrying the P301L mutation, which is
      associated with frontotemporal dementia with parkinsonism. Within 1 month of in
      situ transfection of the basal forebrain region of normal rats, tau
      immunoreactive and argyrophilic neuronal lesions formed. The fibrillar lesions
      had features of neurofibrillary tangles and tau immunoreactivity at light and
      electron microscopic levels. In addition to neurofibrillary tangles, other tau
      pathology, including pretangles and neuropil threads, was abundant and
      widespread. Tau gene transfer to the hippocampal region of amyloid-depositing
      transgenic mice produced pretangles and threads, as well as intensely tau
      immunoreactive neurites in amyloid plaques. The ability to produce
      neurofibrillary pathology in adult rodents makes this a useful method to study
      tau-related neurodegeneration.

PMID- 14695346
TI  - Cysteine 10 is a key residue in amyloidogenesis of human transthyretin Val30Met.
AB  - Type I familial amyloidotic polyneuropathy (FAP), a systemic amyloidosis, is
      characterized by aggregation of variant transthyretin (TTR Val30Met) into stable,
      insoluble fibrils. This aggregation is caused by genetic and environmental
      factors. Genetic factors have been studied extensively. However, little is known
      about environmental or physiological factors involved in the disease process, and
      their identification may be important for development of effective treatment. X
      ray crystallography of normal and amyloidogenic human TTR Val30Met in type I FAP
      showed that the -SH side chain of cysteine at position 10 (Cys10) forms a
      hydrogen bond with Gly57 in normal TTR but not in TTR Val30Met. This result
      suggests a crucial role for the free Cys10 residue and possible involvement of
      physiological factors affecting Cys residue reactivity in TTR amyloidogenesis. To
      analyze amyloidogenesis in vivo, our group generated murine FAP models by
      transgenic technology, with human TTR Val30Met. The three lines of transgenic
      mice expressed amyloidogenic mutant TTR (Cys10/Met30), wild-type TTR
      (Cys10/Val30), and artificial Cys-free mutant TTR (Ser10/Met30). Histochemical
      investigation showed deposition of amyloid derived from human TTR only in
      amyloidogenic mutant TTR (Cys10/Met30) mice. Thus, the -SH residue in Cys10 plays
      a crucial role in TTR Val30Met amyloidogenesis in vivo. These data suggest the
      possibility of innovative treatment via physiological factors modulating Cys10
      residue reactivity.

PMID- 14695348
TI  - Galanin inhibits gut-related vagal neurons in rats.
AB  - Galanin plays an important role in the regulation of food intake, energy balance,
      and body weight. Many galanin-positive fibers as well as galanin-positive neurons
      were seen in the dorsal vagal complex, suggesting that galanin produces its
      effects by actions involving vagal neurons. In the present experiment, we used
      tract-tracing and neurophysiological techniques to evaluate the origin of the
      galaninergic fibers and the effect of galanin on neurons in the dorsal vagal
      complex. Our results reveal that the nucleus of the solitary tract is the major
      source of the galanin terminals in the dorsal vagal complex. In vivo experiments
      demonstrated that galanin inhibited the majority of gut-related neurons in the
      dorsal motor nucleus of the vagus. In vitro experiments demonstrated that galanin
      inhibited the majority of stomach-projecting neurons in the dorsal motor nucleus
      of the vagus by suppressing spontaneous activity and/or producing a fully
      reversible dose-dependent membrane hyperpolarization and outward current. The
      galanin-induced hyperpolarization and outward current persisted after synaptic
      input was blocked, suggesting that galanin acts directly on receptors of neurons
      in the dorsal motor nucleus of the vagus. The reversal potential induced by
      galanin was close to the potassium ion potentials of the Nernst equation and was
      prevented by the potassium channel blocker tetraethylammonium, indicating that
      the inhibitory effect of galanin was mediated by a potassium channel. These
      results indicate that the dorsal motor nucleus of the vagus is inhibited by
      galanin derived predominantly from neurons in the nucleus of the solitary tract
      projecting to the dorsal motor nucleus of the vagus nerve. Galanin is one of the
      neurotransmitters involved in the vago-vagal reflex.

PMID- 14695349
TI  - Nonlinear encoding of tactile patterns in the barrel cortex.
AB  - Cells in the rodent barrel cortex respond to vibrissa deflection with a brief
      excitatory component and a longer suppressive component. The response to a given
      deflection is thus scaled because of suppression induced by a preceding
      deflection, causing the neuronal response to be linked to the temporal properties
      of the peripheral stimulus. A paired-deflection stimulus was used to characterize
      the postexcitatory suppression and a 3-deflection stimulus was used to
      investigate the nonlinear response to patterns of whisker deflections in
      barbiturate-anesthetized Sprague-Dawley rats. The postexcitatory suppression was
      not dependent on a sensory-evoked action potential to the first deflection,
      implying that it is likely a subthreshold property of the network. The
      suppression induced by a deflection served to suppress both the excitatory and
      suppressive components of a subsequent neuronal response, thus effectively
      disinhibiting it. Two different response properties were observed in the recorded
      cells. Approximately 65% responded to a vibrissa deflection with an excitatory
      component followed by a suppressive component and 35% responded with excitation,
      suppression, and a subsequent rebound in excitation. Based on these observations
      of postexcitatory dynamics, a prediction method was used to estimate neuronal
      responses to more complex stimulus trains. Using the 2nd-order representation
      obtained from the paired-deflection stimulus, responses to general periodic
      deflection patterns were well predicted. A higher cutoff frequency was predicted
      for rebound cells compared with cells not exhibiting rebound excitation,
      consistent with experimental observations. The method also predicted the response
      of neurons to a random aperiodic deflection pattern. Therefore the temporal
      structure of cortical dynamics after a single deflection dictates the response to
      complex temporal patterns, which are more representative of stimuli encountered
      under natural conditions.

PMID- 14695350
TI  - Responses and afferent pathways of C1-C2 spinal neurons to cervical and thoracic
      esophageal stimulation in rats.
AB  - Because vagal and sympathetic inputs activate upper cervical spinal neurons, we
      hypothesized that stimulation of the esophagus would activate C(1)-C(2) neurons.
      This study examined responses of C(1)-C(2) spinal neurons to cervical and
      thoracic esophageal distension (CED, TED) and afferent pathways for CED and TED
      inputs to C(1)-C(2) spinal neurons. Extracellular potentials of single C(1)-C(2)
      spinal neurons were recorded in pentobarbital-anesthetized male rats. Graded CED
      or TED was produced by water inflation (0.1-0.5 ml) of a latex balloon. CED
      changed activity of 48/219 (22%) neurons; 34 were excited (E), 12 were inhibited
      (I), and 2 were E-I. CED elicited responses for 18/18 neurons tested after
      ipsilateral cervical vagotomy, for 12/14 neurons tested after bilateral vagotomy
      and for 9/11 neurons tested after bilateral vagotomy and C(6)-C(7) spinal cord
      transection. TED changed activity of 31/190 (16%) neurons (28E, 3 I). Ipsilateral
      cervical vagotomy abolished TED-evoked responses of 5/12 neurons. Bilateral
      vagotomy eliminated responses of 2/4 neurons tested, and C(6)-C(7) spinal
      transection plus bilateral vagotomy eliminated responses of 2/2 neurons. Thus
      inputs from CED to C(1)-C(2) neurons most likely entered upper cervical dorsal
      roots, whereas inputs from TED were dependent on vagal pathways and/or
      sympathetic afferent pathways that entered the thoracic dorsal roots. These
      results supported a concept that C(1)-C(2) spinal neurons play a role in
      integrating visceral information from cervical and thoracic esophagus.

PMID- 14695351
TI  - Small-conductance Ca2+-dependent K+ channels are the target of spike-induced Ca2+
      release in a feedback regulation of pyramidal cell excitability.
AB  - Cooperative regulation of inosiol-1,4,5-trisphosphate receptors (IP(3)Rs) by
      Ca(2+) and IP(3) has been increasingly recognized, although its functional
      significance is not clear. The present experiments first confirmed that
      depolarization-induced Ca(2+) influx triggers an outward current in visual cortex
      pyramidal cells in normal medium, which was mediated by apamin-sensitive, small
      conductance Ca(2+)-dependent K(+) channels (SK channels). With IP(3)-mobilizing
      neurotransmitters bath-applied, a delayed outward current was evoked in addition
      to the initial outward current and was mediated again by SK channels. Calcium
      turnover underlying this biphasic SK channel activation was investigated. By
      voltage-clamp recording, Ca(2+) influx through voltage-dependent Ca(2+) channels
      (VDCCs) was shown to be responsible for activating the initial SK current,
      whereas the IP(3)R blocker heparin abolished the delayed component. High-speed
      Ca(2+) imaging revealed that a biphasic Ca(2+) elevation indeed underlays this
      dual activation of SK channels. The first Ca(2+) elevation originated from VDCCs,
      whereas the delayed phase was attributed to calcium release from IP(3)Rs. Such
      enhanced SK currents, activated dually by incoming and released calcium, were
      shown to intensify spike-frequency adaptation. We propose that spike-induced
      calcium release from IP(3)Rs leads to SK channel activation, thereby fine tuning
      membrane excitability in central neurons.

PMID- 14695352
TI  - Electrophysiological and morphological characterization of identified motor
      neurons in the Drosophila third instar larva central nervous system.
AB  - We have used dye fills and electrophysiological recordings to identify and
      characterize a cluster of motor neurons in the third instar larval ventral
      ganglion. This cluster of neurons is similar in position to the well-studied
      embryonic RP neurons. Dye fills of larval dorsomedial neurons demonstrate that
      individual neurons within the cluster can be reproducibly identified by observing
      their muscle targets and bouton morphology. The terminal targets of these five
      neurons are body wall muscles 6/7, 1, 14, and 30 and the intersegmental nerve
      (ISN) terminal muscles (1, 2, 3, 4, 9, 10, 19, 20). All cells except the ISN
      neuron, which has a type Is ending, display type Ib boutons. Two of these neurons
      appear to be identical to the embryonic RP3 and aCC cells, which define the most
      proximal and distal innervations within a hemisegment. The targets of the other
      neurons in the larval dorsomedial cluster do not correspond to embryonic targets
      of the neurons in the RP cluster, suggesting rewiring of this circuit during
      early larval stages. Electrophysiological studies of the five neurons in current
      clamp revealed that type Is neurons have a longer delay in the appearance of the
      first spike compared with type Ib neurons. Genetic, biophysical, and
      pharmacological studies in current and voltage clamp show this delay is
      controlled by the kinetics and voltage sensitivity of inactivation of a current
      whose properties suggest that it may be the Shal I(A) current. The combination of
      genetic identification and whole cell recording allows us to directly explore the
      cellular substrates of neural and locomotor behavior in an intact system.

PMID- 14695353
TI  - Evidence that phospholipase D activation prevents group I mGluR-induced
      persistent prolongation of epileptiform bursts.
AB  - Selective activation of group I metabotropic glutamate receptors (mGluRs) with
      (S)-3,5-dihydroxyphenylglycine (DHPG) in guinea pig hippocampal slices converts
      275- to 475-ms picrotoxin-induced interictal bursts into persistent seizure
      length discharges typically over 1 s in duration. Here we report that l-cysteine
      sulfinic acid (CSA), a sulfur-containing amino acid, prevented the induction of
      this persistent group I mGluR-mediated epileptiform burst prolongation. However,
      CSA had no effect on baseline interictal bursting activity and failed to suppress
      the expression of the group I mGluR-induced persistent prolonged bursts once they
      were fully induced. (2R,1'S,2'R,3'S)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine
      (PCCG-13), a selective antagonist at the phospholipase D (PLD)-coupled mGluR, had
      no effect of its own on DHPG-induced burst prolongation; however, CSA applied in
      the presence of PCCG-13 could no longer fully block the burst prolongation
      induced by DHPG, suggesting that CSA's antiepileptogenic effect is mediated by
      agonist action at this PLD-coupled receptor. These data parallel our previous
      data revealing that protein synthesis inhibitors prevent induction but not
      expression of group I mGluR-mediated persistent seizure-length discharges. Hence,
      PLD activation with CSA may prevent the synthesis of a protein critical for the
      induction of group I mGluR-mediated epileptogenesis.

PMID- 14695354
TI  - Movement reduces the dynamic response of muscle spindle afferents and motoneuron
      synaptic potentials in rat.
AB  - Among the mechanisms that may result in modulation of the stretch reflex by the
      recent history of muscle contraction is the history dependence observed under
      some conditions in the response properties of muscle spindles. The present study
      was designed to test one report that in successive trials of muscle stretch
      release, spindle afferent firing during stretch, i.e., the dynamic response shows
      no history dependence beyond the initial burst of firing at stretch onset. Firing
      responses of spindle afferents were recorded during sets of three consecutive
      trials of triangular stretch-release applied to triceps surae muscles in
      barbiturate-anesthetized rats. All 69 spindle afferents fired more action
      potentials (spikes) during the dynamic response of the first trial, excluding the
      initial burst, than in the following two trials. The reduced dynamic response
      (RDR) was nearly complete after trial 1 and amounted to an average of
      approximately 12 fewer spikes (16 pps slower firing rate) in trial 3 than in
      trial 1. RDR was sensitive to the interval between stretch sets but independent
      of stretch velocity (4-32 mm/s). RDR was reflected in the synaptic potentials
      recorded intracellularly from 16 triceps surae alpha-motoneurons: depolarization
      during muscle stretch was appreciably reduced after trial 1. These findings
      demonstrate history dependence of spindle afferent responses that extends
      throughout the dynamic response in successive muscle stretches and that is
      synaptically transmitted to motoneurons with the probable effect, unless
      otherwise compensated, of modulating the stretch reflex.

PMID- 14695357
TI  - Gain-of-function polymorphism in mouse and human Ltk: implications for the
      pathogenesis of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE), a complex multigenic disease, is a typical
      antibody-mediated autoimmune disease characterized by production of
      autoantibodies against a variety of autoantigens and immune complex-type tissue
      inflammation, most prominently in the kidney. Evidence suggests that genetic
      factors predisposing to aberrant proliferation/maturation of self-reactive B
      cells initiate and propagate the disease. In SLE-prone New Zealand Black (NZB)
      mice and their F1 cross with New Zealand White (NZW) mice, B cell abnormalities
      can be ascribed mainly to self-reactive CD5+ B1 cells. Our genome-wide scans to
      search for susceptibility genes for aberrant activation of B1 cells in these mice
      showed evidence that the gene, Ltk, encoding leukocyte tyrosine kinase (LTK), is
      a possible candidate. LTK is a receptor-type protein tyrosine kinase, belonging
      to the insulin receptor superfamily, and is mainly expressed in B lymphocyte
      precursors and neuronal tissues. Sequence and functional analyses of the gene
      revealed that NZB has a gain-of-function polymorphism in the LTK kinase domain
      near YXXM, a binding motif of the p85 subunit of phosphatidylinositol 3-kinase
      (PI3K). SLE patients also had this type of Ltk polymorphism with a significantly
      higher frequency compared with the healthy controls. Our findings suggest that
      these polymorphic LTKs cause up-regulation of the PI3K pathway and possibly form
      one genetic component of susceptibility to abnormal proliferation of self
      reactive B cells in SLE.

PMID- 14695358
TI  - Twenty-first century health promotion: the public health revolution meets the
      wellness revolution.

PMID- 14695359
TI  - Change in health risk perception following community intervention in Central
      Havana, Cuba.
AB  - It is increasingly recognized that individual values, beliefs and behavior
      operate within a social context. There is growing consensus that local
      perceptions and indigenous knowledge should be important elements in the
      evaluation of programs aimed at improving health. Thus, an assessment of changes
      in health risk perception was included in the evaluation of a multi-component
      intervention project undertaken between 1996 and 1999 aimed at improving the
      health and well-being of residents in the inner city community of Cayo Hueso, in
      Centro Habana, Cuba. The community intervention involved a tremendous
      mobilization of government and non-governmental organizations, to promote social
      and cultural activities and address deficiencies in housing, water supply, waste
      disposal and street illumination. Prior to the interventions, 365 adults were
      surveyed regarding their perceived health risks regarding 41 health determinants,
      scored on four-point Likert scales ranging from 'without risk' to 'very risky'. A
      factor analysis of these data classified perception of risk into five areas:
      social environment, threats to personal health, lifestyle choices, environmental
      sanitation and housing conditions. The objective of the current analysis was to
      determine if there were changes in the level of perceived risk to health over the
      5 years pre- versus post-intervention in Cayo Hueso, and if so, whether these
      changes were significantly different from changes seen during the same 5-year
      period in Colon, another community in Centro Habana not receiving focused
      interventions. During the first quarter of 2001, 1703 individuals living in 654
      households in Cayo Hueso and Colon were interviewed in their homes using an
      enhanced version of the 1996 risk perception instrument. Ordinal logistic
      regression models, adjusted for age, gender and years of education, were fit to
      assess change in health risk perception between 1996 and 2001. Significant
      declines in perceived health risk were found in both Cayo Hueso and Colon within
      all five domains, with significantly greater declines in many areas in Cayo Hueso
      compared with Colon, particularly with respect to housing-related health risks,
      indeed the main target of the intervention. Risk perception surveys are useful
      characterizations of widely held views in a target population. Our findings of
      decreased perceived health risk following public health, physical and social
      interventions to improve health suggests that this line of inquiry merits
      consideration in planning evaluations of multi-sectoral community-based health
      promotion interventions.

PMID- 14695360
TI  - Evaluation of a pilot school programme aimed at the prevention of obesity in
      children.
AB  - This paper describes the development, implementation and evaluation of a school-
      and family-based intervention to prevent obesity in children aged 5-7 years. In
      addition, the efficacy of three different intervention programmes was compared.
      Children aged 5-7 years (n=213) were recruited from three primary schools in
      Oxford and randomly allocated to a control group or one of three intervention
      groups: nutrition group, physical activity group, and combined nutrition and
      physical activity group. The setting for the interventions was lunchtime clubs,
      where an interactive and age-appropriate nutrition and/or physical activity
      curriculum was delivered. The intervention lasted for 20 weeks over four school
      terms (approximately 14 months). Children's growth, nutrition knowledge, diet and
      physical activity were assessed at baseline and at the end of the intervention.
      Significant improvements in nutrition knowledge were seen in all children
      (p<0.01) between baseline and post-intervention, and results were highly
      significant in the nutrition and combined group (p<0.001). Overall, fruit and
      vegetable intake increased significantly (p<0.01 and <0.05, respectively), with
      changes seen in fruit consumption in the nutrition group (p<0.05) and the control
      group (p<0.05) in particular. No significant changes in the rates of overweight
      and obesity were seen as a result of the intervention. Gender differences were
      not detected in the majority of assessments and there was no clear effect of
      programme type per se. This pilot study has demonstrated that school may be a
      suitable setting for the promotion of healthy lifestyles in children, but
      requires replication in other social settings. Future initiatives should be long
      lasting, multi-faceted and sustainable, involving all children in a school, and
      should target the whole environment and be behaviourally focused. The ultimate
      goal of any such programme is to lead to positive behaviour change which will
      have a beneficial effect on long-term health. Successful targeting of the family
      remains a challenge to such interventions.

PMID- 14695361
TI  - Individual versus corporate responsibility for smoking-related illness:
      Australian press coverage of the Rolah McCabe trial.
AB  - This paper provides a thematic frame analysis of Australian newspaper reporting
      of the outcome and implications of the trial of Rolah McCabe versus British
      American Tobacco Australasia (BATA). In this trial, a Melbourne woman was awarded
      A$700,000 damages for smoking-attributable lung cancer when the defendant, BATA,
      had its case dismissed due to document destruction. In 60 commentaries from
      Australian national or capital city newspapers between 12 April and 9 May 2002, a
      total of 79 instances of eight tobacco-related frames were identified. Overall,
      43% of the 79 instances were positive for tobacco control, 46% were negative for
      tobacco control and 11% were neutral. The most common frame that was negative for
      tobacco control (in 35% of articles) was the conception that smokers exert 'free
      will' in deciding to smoke and should therefore be personally responsible for
      their smoking and any disease that arises as a result of it. A related, but less
      commonly employed frame (in 18% of articles) was the expressed fear of a
      'slippery slope' of litigation, which portrayed smoking as similar to eating fast
      food or other 'vices'. The most common frame that was positive for tobacco
      control (in 35% of articles) was the notion that the tobacco industry was 'evil'
      and, to a lesser extent, that the government should 'do more' to control smoking
      (15% of articles). These findings provide a sobering public health challenge to
      improve public communication efforts about the powerful forces that conspire to
      induce people to start smoking and keep them smoking for decades, despite a
      strong desire to quit. There is a need to fund public education programs and quit
      smoking services more adequately to address the complex education task of
      understanding the nature of addiction to tobacco and the enormity of the health
      risk.

PMID- 14695362
TI  - Hard boys, attractive girls: expressions of gender in young people's
      conversations on smoking in Northern Ireland.
AB  - Health behaviour and attitudes among young people can be interpreted within the
      context of personal and social identity. This paper explores ways in which 10- to
      11-year-olds in Northern Ireland expressed perceptions of gender ideology while
      discussing the topic of smoking. The data were gathered by means of in-depth
      interviews (n=85). Although few had tried smoking, the positive quality of their
      own gender appeared to be expressed through negative assessment of smokers of the
      opposite gender, and on different ideas of perceived gender dimensions in adult
      smoking. In order to deliver successful health promotion interventions, it is
      crucial to understand and address differences based on gender as it may partly
      explain differences in smoking experimentation and prevalence.

PMID- 14695363
TI  - Smoking cessation in New Zealand: education and resources for use by midwives for
      women who smoke during pregnancy.
AB  - This study describes the development and evaluation of education programmes and
      associated resource materials to support smoking cessation and reduction, and
      breastfeeding promotion strategies for pregnant women who smoke, during usual
      primary maternity care by midwives. Education programmes and resource materials
      were developed by midwives and researchers as part of a cluster randomized trial
      of Midwifery Education for Women who Smoke (the MEWS study). Development included
      a cohort study, advice from lactation consultants and smoking cessation
      counsellors (including Ma-ori professionals), and early consultation with
      midwives who would be delivering the programmes. Resources developed included
      videotapes, charts and laminated information cards. Resources were pre-tested
      with pregnant women and opinion leaders. Consultation with the midwives allocated
      to each of the intervention groups in the trial raised a number of issues. These
      were addressed, and solutions incorporated into each of the programmes, to enable
      effective delivery within usual care. Following delivery of the programmes, women
      and their midwives were surveyed and a sample interviewed to ascertain attitudes
      to the programmes and resources. Women and their midwives responded positively to
      the smoking cessation education programme, the breastfeeding promotion programme
      and the resources used. Those women who did not stop smoking completely often
      succeeded in significantly reducing their tobacco consumption. Women identified
      their midwife as a valuable resource and appreciated her ongoing encouragement.
      Involvement of health professionals who are to deliver health promotion
      interventions is essential for successful integration of programmes into usual
      care. Midwives were able to effectively deliver programmes that were developed
      and targeted to their needs as health educators. The pregnancy-specific resources
      developed for women who smoke played an important part in helping midwives
      deliver their health promotion messages more effectively.

PMID- 14695364
TI  - Determinants of the use of maternal health services in rural Bangladesh.
AB  - Utilization of health services is a complex behavioral phenomenon. Empirical
      studies of preventive and curative services have often found that use of health
      services is related to the availability, quality and cost of services, as well as
      to social structure, health beliefs and personal characteristics of the users. In
      this paper an attempt is made to examine the factors associated with the use of
      maternal health care services in Bangladesh on the basis of data from a survey of
      maternal morbidity in Bangladesh, conducted by the Bangladesh Institute of
      Research for Promotion of Essential and Reproductive Health and Technologies
      (BIRPERHT). The results from both the bivariate and multivariate analyses
      confirmed the importance of mother's education in explaining the utilization of
      health care services. Female education retains a net effect on maternal health
      service use, independent of other women's background characteristics, household's
      socioeconomic status and access to healthcare services. The strong influence of
      mother's education on the utilization of health care services is consistent with
      findings from other studies. Women whose husbands are involved in
      business/services also positively influenced the utilization of modern health
      care services. However, the study results are inconclusive with respect to the
      influence of other predisposing and enabling factors, such as women's age, number
      of previous pregnancies and access to health facilities. Multivariate logistic
      regression estimates do not show any significant impact of these factors on the
      use of maternal health care. The influence of severity of disease condition in
      explaining the utilization of maternal health care appears to be significant.
      Multivariate analysis indicate that women having had a life-threatening condition
      are little over two times more likely to seek care from a doctor or nurse to
      treat their maternal morbidities.

PMID- 14695365
TI  - Working with Toronto neighbourhoods toward developing indicators of community
      capacity.
AB  - Often the goal of health and social development agencies is to assess communities
      and work with them to improve community capacity. Particularly for health
      promoters working in community settings and to ensure consistency in the
      definition of health promotion, the evaluation of health promotion programmes
      should be based on strengths and assets, yet existing information for planning
      and evaluation purposes usually focuses on problems and deficits. A model and
      definition of community capacity, grounded in community experience and focusing
      on strengths and assets, was developed following a 4-year, multi-site,
      qualitative, action research project in four Toronto neighbourhoods. There was
      significant community involvement in the four Community Advisory Committees, one
      for each study site. Semi-structured, open-ended interviews and focus groups were
      conducted with 161 residents and agency workers identified by the Community
      Advisory Committees. The data were analyzed with the assistance of NUDIST
      software. Thematic analysis was undertaken in two stages: (i) within each site
      and (ii) across sites, with the latter serving as the basis for the development
      of indicators of community capacity. This paper presents a summary of the
      research, the model and the proposed indicators. The model locates talents and
      skills of community members in a larger context of socioenvironmental conditions,
      both inside and outside the community, which can act to enable or constrain the
      expression of these talents and skills. The significance of the indicators of
      community capacity proposed in the study is that they focus on identifying and
      measuring the facilitating and constraining socioenvironmental conditions.

PMID- 14695366
TI  - Building health promoting work settings: identifying the relationship between
      work characteristics and occupational stress in Australia.
AB  - Occupational stress is a serious threat to the health of individual workers,
      their families and the community at large. The settings approach to health
      promotion offers valuable opportunities for developing comprehensive strategies
      to prevent and reduce job stress. However, there is evidence that many workplace
      health promotion programs adopt traditional, lifestyle-oriented strategies when
      dealing with occupational stress, and ignore the impact that the setting itself
      has on the health of employees. The aim of the present study was to address two
      of the barriers to adopting the settings approach; namely the lack of information
      on how psycho-social work characteristics can influence health, and not having
      the confidence or knowledge to identify or address organizational-level issues. A
      comprehensive occupational stress audit involving qualitative and quantitative
      research methods was undertaken in a small- to medium-sized public sector
      organization in Australia. The results revealed that the work characteristics
      'social support' and 'job control' accounted for large proportions of explained
      variance in job satisfaction and psychological health. In addition to these
      generic variables, several job-specific stressors were found to be predictive of
      the strain experienced by employees. When coupled with the results of other
      studies, these findings suggest that work characteristics (particularly control
      and support) offer valuable avenues for creating work settings that can protect
      and enhance employee health. The implications of the methods used to develop and
      complete the stress audit are also discussed.

PMID- 14695367
TI  - What picture is worth a thousand words? A comparative evaluation of a burn
      prevention programme by type of medium in Israel.
AB  - Burns are associated with longer hospital stay, permanent disfigurement and
      emotional stress disorders, and represent a health problem, especially among
      economically and socially deprived populations, such as the Bedouin population in
      Israel, hence the importance of intervention programmes. The objective of this
      research was to examine the extent to which the effect of a visual one-session
      burn prevention programme was determined by the type of medium used. We also
      examined the possibility that fear motivates action only when someone feels
      confident in his/her ability to control the threat. Data were based on the pre
      /post-programme self-report questionnaires administered to a randomly selected
      three-group sample of 12- to 13-year-old Bedouin children (n=179). All three
      sessions were identical, but differed in the type of medium used: slides (S),
      video (V), or slides and video consecutively (S + V). We measured health beliefs
      (perceived threat, internal/external control, self-efficacy) and sense of
      coherence (SOC), both before and 2 months after completion of the intervention.
      We also measured post-programme fear reaction and the improvement in burn-related
      knowledge, understanding and safety behaviour as the outcome measure. No
      significant post-programme differences between intervention groups were found,
      either in terms of outcome measure or in terms of health beliefs and SOC.
      However, within- person analysis indicated that the S group participants had the
      highest level of post-exposure fear and a decrease in luck control over injuries.
      The S + V group demonstrated the lowest within change. The hierarchical
      regression analysis revealed that self-efficacy, fear, higher socio-economic
      status and female gender predicted improvement. As hypothesized, the interaction
      between fear and self-efficacy added significantly to prediction. It seems that
      health beliefs and demographic characteristics were more powerful in predicting
      the effect of the intervention than the choice of medium per se. A multifaceted
      approach and more comprehensive interventions are needed in order to promote
      health among disadvantaged populations.

PMID- 14695368
TI  - Tobacco control and gender in south-east Asia. Part II: Singapore and Vietnam.
AB  - In the World Health Organization's Western Pacific Region, being born male is the
      single greatest risk marker for tobacco use. While the literature demonstrates
      that risks associated with tobacco use may vary according to sex, gender refers
      to the socially determined roles and responsibilities of men and women, who
      initiate, continue and quit using tobacco for complex and often different
      reasons. Cigarette advertising frequently appeals to gender roles. Yet tobacco
      control policy tends to be gender-blind. Using a broad, gender-sensitivity
      framework, this contradiction is explored in four Western Pacific countries. Part
      I of the study presented the rationale, methodology and design of the study,
      discussed issues surrounding gender and tobacco, and analysed developments in
      Malaysia and the Philippines (see the previous issue of this journal). Part II
      deals with Singapore and Vietnam. In all four countries gender was salient for
      the initiation and maintenance of smoking. Yet, with a few exceptions, gender was
      largely unrecognized in control policy. Suggestions for overcoming this weakness
      in order to enhance tobacco control are made.

PMID- 14695369
TI  - Shortcomings of health information on the Internet.
AB  - Disseminating health and medical information on the Internet can improve
      knowledge transfer from health professionals to the population, and help
      individuals to maintain and improve their health. There are currently several
      medical information websites that directly target the general population with the
      aim of providing information about health problems, self-care and prevention.
      However, this new technology also hides several shortcomings, such as: (i) uneven
      quality of medical information available on the Internet; (ii) difficulties in
      finding, understanding and using this information; (iii) lack of access for the
      unconnected population; and (iv) the potential for harm and risks of over
      consumption. To be able to overcome these dangers, it is important that public
      health practitioners and health professionals be involved in the design,
      dissemination and evaluation of Web-based health and medical information.

PMID- 14695370
TI  - Comprehensive approaches to school health promotion: how to achieve broader
      implementation?
AB  - The Health Promoting School (HPS) and Comprehensive School Health Program (CSHP)
      initiatives have been proposed as a means of going beyond some of the limitations
      associated with health promotion initiatives aimed at school-aged children. This
      involves moving beyond practices that rely mainly on classroom-based health
      education models, to a more comprehensive, integrated approach of health
      promotion that focuses both on child-youth attitudes and behaviors, and their
      environment. Despite the tremendous potential of these initiatives in terms of
      health and educational gains, only rarely are they actually put into practice.
      This article briefly reviews the features of these initiatives, as well as the
      extent of their implementation and current benefits. Against that backdrop, the
      authors identify some issues to consider and propose four conditions with a view
      to achieving broader practical application of these approaches. These issues,
      which are discussed from the standpoint of potential avenues of further study and
      courses of action, relate to the comprehensive, integrated nature of the
      intervention, the school/family/community partnership, political and financial
      support from policy makers, and, finally, evaluative research as a support to
      implementation.

PMID- 14695371
TI  - Barriers to addressing the societal determinants of health: public health units
      and poverty in Ontario, Canada.
AB  - Despite Canada's reputation as a leader in health promotion and population health
      concepts, actual public health practice for the most part remains wedded to
      downstream strategies focussed on behaviour change. In Canada's largest province
      this has led to the implementation of a heart health promotion approach focussed
      on diet, activity and tobacco use. This is so despite increasing evidence that
      these approaches are generally ineffective, particularly for those at greatest
      risk. In addition, these strategies appear to divert public and governmental
      attention away from addressing the broader societal determinants of health.
      Examples of Ontario public health units that have begun to address societal
      determinants of health provide a counterbalance to the dominant paradigm that
      frames health as an individual responsibility. These new approaches focus
      attention upon the health-threatening effects of governments' regressive social
      and economic policies in a manner consistent with the best principles of health
      promotion.

PMID- 14695373
TI  - Sperm from beta1,4-galactosyltransferase I-null mice exhibit precocious
      capacitation.
AB  - Mammalian sperm must undergo a physiological maturation, termed capacitation,
      before they are able to fertilize eggs. Despite its importance, the molecular
      mechanisms underlying capacitation are poorly understood. In this paper, we
      describe the capacitation phenotype of sperm lacking the long isoform of beta1,4
      galactosyltransferase I (GalT I), a sperm surface protein that functions as a
      receptor for the zona pellucida glycoprotein, ZP3, and as an inducer of the
      acrosome reaction following ZP3-dependent aggregation. As expected, wild-type
      sperm must undergo capacitation in order to bind the zona pellucida and undergo a
      Ca(2+) ionophore-induced acrosome reaction. By contrast, GalT I-null sperm behave
      as though they are precociously capacitated, in that they demonstrate maximal
      binding to the zona pellucida and greatly increased sensitivity to ionophore
      induced acrosome reactions without undergoing capacitation in vitro. The loss of
      GalT I from sperm results in an inability to bind epididymal glycoconjugates that
      normally maintain sperm in an 'uncapacitated' state; removing these
      decapacitating factors from wild-type sperm phenocopies the capacitation behavior
      of GalT I-null sperm. Interestingly, capacitation of GalT I-null sperm is
      independent of the presence of albumin, Ca(2+) and HCO(3)(-); three co-factors
      normally required by wild-type sperm to achieve capacitation. This implies that
      intracellular targets of albumin, Ca(2+) and/or HCO(3)(-) may be constitutively
      active in GalT I-null sperm. Consistent with this, GalT I-null sperm have
      increased levels of cAMP that correlate closely with both the accelerated
      kinetics and co-factor-independence of GalT I-null sperm capacitation. By
      contrast, the kinetics of protein tyrosine phosphorylation and sperm motility are
      unaltered in mutant sperm relative to wild-type. These data suggest that GalT I
      may function as a negative regulator of capacitation in the sperm head by
      suppressing intracellular signaling pathways that promote this process.

PMID- 14695374
TI  - Characterization of a novel ZP3-independent sperm-binding ligand that facilitates
      sperm adhesion to the egg coat.
AB  - During mammalian fertilization, sperm adhere to the extracellular coat of the
      egg, or zona pellucida, in a species-specific manner. In mouse, evidence suggests
      that sperm recognize and bind to specific oligosaccharide ligands within the zona
      pellucida glycoprotein, ZP3, via beta1,4-galactosyltransferase I (GalT I), a
      lectin-like receptor on the sperm surface. Although in vitro experiments using
      isolated gametes lend support to this model, recent in vivo studies of
      genetically altered mice question whether ZP3 and/or GalT I are solely
      responsible for sperm-egg binding. In this regard, sperm from GalT I-null mice
      bind poorly to ZP3 and fail to undergo a zona-induced acrosome reaction; however,
      they still bind to the ovulated egg coat in vitro. In this report, we
      characterize a novel ZP3- and GalT I-independent mechanism for sperm adhesion to
      the egg coat. Results show that the ovulated zona pellucida contains at least two
      distinct ligands for sperm binding: a ZP3-independent ligand that is peripherally
      associated with the egg coat and facilitates gamete adhesion; and a ZP3-dependent
      ligand that is present in the insoluble zona matrix and is recognized by sperm
      GalT I to facilitate acrosomal exocytosis. The ZP3-independent ligand is not a
      result of contamination by egg cortical granules, nor is it the mouse homolog of
      oviduct-specific glycoprotein. It behaves as a 250 kDa, WGA-reactive glycoprotein
      with a basic isoelectric point, distinguishing it from the acidic glycoproteins
      that form the insoluble matrix of the egg coat. When eluted from isoelectric
      focusing gels, the acidic matrix glycoproteins possess sperm-binding activity for
      wild-type sperm, but not for GalT I-null sperm, whereas the basic glycoprotein
      retains sperm-binding activity for both wild-type and GalT I-null sperm. Thus,
      GalT I-null sperm are able to resolve gamete recognition into at least two
      distinct binding events, leading to the characterization of a novel, peripherally
      associated, sperm-binding ligand on the ovulated zona pellucida.

PMID- 14695375
TI  - Six1 controls patterning of the mouse otic vesicle.
AB  - Six1 is a member of the Six family homeobox genes, which function as components
      of the Pax-Six-Eya-Dach gene network to control organ development. Six1 is
      expressed in otic vesicles, nasal epithelia, branchial arches/pouches,
      nephrogenic cords, somites and a limited set of ganglia. In this study, we
      established Six1-deficient mice and found that development of the inner ear,
      nose, thymus, kidney and skeletal muscle was severely affected. Six1-deficient
      embryos were devoid of inner ear structures, including cochlea and vestibule,
      while their endolymphatic sac was enlarged. The inner ear anomaly began at around
      E10.5 and Six1 was expressed in the ventral region of the otic vesicle in the
      wild-type embryos at this stage. In the otic vesicle of Six1-deficient embryos,
      expressions of Otx1, Otx2, Lfng and Fgf3, which were expressed ventrally in the
      wild-type otic vesicles, were abolished, while the expression domains of Dlx5,
      Hmx3, Dach1 and Dach2, which were expressed dorsally in the wild-type otic
      vesicles, expanded ventrally. Our results indicate that Six1 functions as a key
      regulator of otic vesicle patterning at early embryogenesis and controls the
      expression domains of downstream otic genes responsible for respective inner ear
      structures. In addition, cell proliferation was reduced and apoptotic cell death
      was enhanced in the ventral region of the otic vesicle, suggesting the
      involvement of Six1 in cell proliferation and survival. In spite of the
      similarity of otic phenotypes of Six1- and Shh-deficient mice, expressions of
      Six1 and Shh were mutually independent.

PMID- 14695377
TI  - Why coat a stent with polymer?

PMID- 14695376
TI  - Requirement of Lim1 for female reproductive tract development.
AB  - Lim1 encodes a LIM-class homeodomain transcription factor that is essential for
      head and kidney development. In the developing urogenital system, Lim1 expression
      has been documented in the Wolffian (mesonephric) duct, the mesonephros,
      metanephros and fetal gonads. Using, a Lim1 lacZ knock-in allele in mice, we
      identified a previously unreported urogenital tissue for Lim1 expression, the
      epithelium of the developing Mullerian duct that gives rise to the oviduct,
      uterus and upper region of the vagina of the female reproductive tract. Lim1
      expression in the Mullerian duct is dynamic, corresponding to its formation and
      differentiation in females and regression in males. Although female Lim1-null
      neonates had ovaries they lacked a uterus and oviducts. A novel female mouse
      chimera assay was developed and revealed that Lim1 is required cell autonomously
      for Mullerian duct epithelium formation. These studies demonstrate an essential
      role for Lim1 in female reproductive tract development.

PMID- 14695382
TI  - Proportions, odds, and risk.
AB  - Perhaps the most common and familiar way that the results of medical research and
      epidemiologic investigations are summarized is in a table of counts. Numbers of
      subjects with and without the outcome of interest are listed for each treatment
      or risk factor group. By using the study sample data thus tabulated,
      investigators quantify the association between treatment or risk factor and
      outcome. Three simple statistical calculations are used for this purpose:
      difference in proportions, relative risk, and odds ratio. The appropriate use of
      these statistics to estimate the association between treatment or risk factor and
      outcome in the relevant population depends on the design of the research. Herein,
      the enumeration of proportions, odds ratios, and risks and the relationships
      between them are demonstrated, along with guidelines for use and interpretation
      of these statistics appropriate to the type of study that gives rise to the data.

PMID- 14695383
TI  - Mammography screening is saving thousands of lives, but will it survive medical
      malpractice?

PMID- 14695384
TI  - Hereditary hemorrhagic telangiectasia of the liver: hyperperfusion with relative
      ischemia--poverty amidst plenty.

PMID- 14695385
TI  - Invasive cancers detected after breast cancer screening yielded a negative
      result: relationship of mammographic density to tumor prognostic factors.
AB  - PURPOSE: To evaluate common breast tumor prognostic characteristics, including
      estrogen receptor (ER) status, grade, size, and method of detection, in
      relationship to mammographic density. MATERIALS AND METHODS: The study involved
      121 women who had negative results at both screening mammography and breast
      physical examination within 17 months before a diagnosis of breast cancer.
      Mammographic density was classified according to Breast Imaging Reporting and
      Data System patterns 1 through 4 (where 1 indicates a fatty breast and 4
      indicates a dense breast). Axillary nodal status and tumor histologic ER status,
      histologic grade, size, stage, and method of detection (mammography alone,
      palpation alone, or both palpation and mammography) were analyzed by density
      category and tested for statistically significant differences across categories
      by using analysis of variance. RESULTS: Statistically significant differences (P
      <.05) by density category were found for the following variables: ER positivity
      (15 of 15 tumors in category 1 breasts, 32 of 41 tumors in category 2 breasts, 37
      of 49 tumors in category 3 breasts, and eight of 16 tumors in category 4 breasts
      were ER positive), occurrence of grade 1 tumors (eight, 11, 19, and four tumors
      in category 1, category 2, category 3, and category 4 breasts, respectively, were
      grade 1), mean tumor size (11.3, 13.0, 14.7, and 19.7 mm for category 1, category
      2, category 3, and category 4 breasts, respectively), detection with mammography
      alone (13, 31, 36, and four tumors in category 1, category 2, category 3, and
      category 4 breasts, respectively, were detected with mammography alone), and
      occurrence of stage I tumors (10, 25, 28, and five tumors in category 1, category
      2, category 3, and category 4 breasts, respectively, were stage I). CONCLUSION:
      In women with negative results at clinical and mammographic screening within 17
      months before breast tumor detection, subsequently diagnosed cancers tend to be
      ER negative, of higher grade, and larger in size in those with dense tissue
      patterns than in those with fat patterns.

PMID- 14695386
TI  - Functional MR imaging versus Wada test for evaluation of language lateralization:
      cost analysis.
AB  - PURPOSE: To compare the total direct costs (fixed and variable costs) of
      functional magnetic resonance (MR) imaging and of the Wada test for evaluation of
      language lateralization. MATERIALS AND METHODS: The direct fixed and variable
      costs of functional MR imaging (performed in 21 patients with mean age +/- SD of
      15.5 years +/- 8.9) and of the Wada test (performed in 18 patients aged 19.2
      years +/- 5.4) were determined prospectively with time and motion analyses. The
      labor of all personnel involved in evaluations of language lateralization was
      tracked, and involvement times were recorded to the nearest minute. All material
      items used in the studies were recorded. Costs of labor and of materials were
      determined from personnel reimbursement data and from vendor pricing,
      respectively. Direct fixed costs were determined from hospital accounting
      department records. Means (+/- SDs) were calculated for all direct fixed and
      variable costs. Total direct costs were determined for each procedure and
      compared by using the Student t test. RESULTS: The total direct costs of the Wada
      test (US dollars 1130.01 +/- US dollars 138.40) and of functional MR imaging (US
      dollars 301.82 +/- US dollars 10.65) were significantly different (P <.001). The
      cost of the Wada test was 3.7 times higher than that of functional MR imaging.
      CONCLUSION: Substantial savings are achievable with the use of functional MR
      imaging instead of the Wada test to evaluate language lateralization.

PMID- 14695387
TI  - Primary and secondary brain tumors at MR imaging: bicentric intraindividual
      crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine.
AB  - PURPOSE: To evaluate the safety of and compare the enhancement characteristics of
      gadobenate dimeglumine (MultiHance; Bracco Imaging, Milan, Italy) with those of a
      standard gadolinium chelate (gadopentetate dimeglumine, Magnevist; Schering,
      Berlin, Germany) in primary and secondary brain tumors on the basis of
      qualitative and quantitative parameters, on an intraindiviual basis. MATERIALS
      AND METHODS: Twenty-seven patients with either high-grade glioma or metastases
      were enrolled in a bicentric intraindividual crossover study to compare lesion
      enhancement with doses of 0.1 mmol per kilogram of body weight of 0.5 mol/L
      gadopentetate dimeglumine and 0.5 mol/L gadobenate dimeglumine. MR imaging was
      performed before injection (T1-weighted spin-echo [SE] and T2-weighted fast SE
      acquisitions) and at 1, 3, 5, 7, 9, and 16 minutes after injection (T1-weighted
      SE acquisitions). Qualitative assessment was performed by blinded off-site
      readers (for 22 patients) and on-site investigators (for 24 patients) in terms of
      global contrast enhancement, lesion-to-brain contrast, lesion delineation,
      internal lesion morphology and structure, tumor vascularization, and global image
      preference. Additional quantitative assessment with region-of-interest analysis
      was performed by off-site readers alone. Statistical analysis of qualitative data
      was performed with the Wilcoxon signed rank test, whereas a nonparametric
      approach was adopted for analysis of quantitative data. RESULTS: Significant (P
      <.05) preference for gadobenate dimeglumine over gadopentetate dimeglumine was
      noted both off-site and on-site for the global assessment of contrast
      enhancement. For off-site readers 1 and 2 and the on-site investigators,
      respectively, gadobenate dimeglumine was preferred in 13, 17, and 16 patients;
      gadopentetate dimeglumine was preferred in four, four, and four patients; and
      equality was found in five, one, and four patients). Similar preference for
      gadobenate dimeglumine was noted by off-site readers and on-site investigators
      for lesion-to-brain contrast and all other qualitative parameters. Off-site
      quantitative evaluation revealed significantly (P <.05) superior enhancement for
      gadobenate dimeglumine compared with that for gadopentetate dimeglumine at all
      time points from 3 minutes after injection. CONCLUSION: Significantly superior
      contrast enhancement of intraaxial enhancing brain tumors was achieved with 0.1
      mmol/kg gadobenate dimeglumine compared with that with 0.1 mmol/kg gadopentetate
      dimeglumine.

PMID- 14695388
TI  - Contralateral high-grade carotid artery stenosis or occlusion is not associated
      with increased risk for poor neurologic outcome after elective carotid stent
      placement.
AB  - PURPOSE: To compare neurologic outcome after elective internal carotid artery
      (ICA) stents have been placed in patients with and in patients without
      contralateral ICA obstructions. MATERIALS AND METHODS: This study included 471
      consecutive patients from a registry database who underwent elective ICA stent
      placement without cerebral protection for high-grade (greater than 70% stenosis
      of the ICA, according to the North American Symptomatic Carotid Endarterectomy
      Trial) symptomatic (n = 147) or asymptomatic (n = 324) ICA stenosis.
      Contralateral carotid arteries were investigated with angiography. Patients with
      and patients without contralateral high-grade stenosis (70%-99% stenosis,
      according to the North American Symptomatic Carotid Endarterectomy Trial) or
      occlusion were compared with respect to 30-day neurologic outcome by using the
      chi2 test and multivariate logistic regression analysis. RESULTS: Neurologic
      events were observed in 33 patients (7%) with 15 transient ischemic attacks,
      eight minor strokes, and 10 major strokes that led to death in two patients
      (combined stroke and death rate, 4%). Eighty-eight patients (19%) with
      contralateral high-grade ICA stenosis and 43 patients (9%) with contralateral ICA
      occlusion exhibited a similar rate of postintervention combined neurologic events
      (n = 9, 7%) compared with patients without contralateral high-grade ICA stenosis
      or occlusion (n = 24, 7%) (P =.94). No differences were observed between
      symptomatic and asymptomatic patients. Combined stroke and death rates were also
      comparable between symptomatic (four of 131, 3%) and asymptomatic (14 of 340, 4%)
      patients (P =.59). Of all variables tested, multivariate analysis did not detect
      any predictor for peri- or postinterventional neurologic events. CONCLUSION:
      Contralateral high-grade ICA stenosis or occlusion was not associated with an
      increased risk for neurologic events after elective ICA stent placement.

PMID- 14695389
TI  - The CT Halo Sign.

PMID- 14695390
TI  - Effect of contrast material injection duration and rate on aortic peak time and
      peak enhancement at dynamic CT involving injection protocol with dose tailored to
      patient weight.
AB  - PURPOSE: To investigate the effect of duration and rate of contrast material
      injection on aortic peak time and peak enhancement in an injection protocol in
      which the contrast material dose is adjusted according to patient weight.
      MATERIALS AND METHODS: One hundred ninety-nine patients were randomly divided
      into three groups in which the fixed duration of contrast material injection was
      25 seconds (group A) or 35 seconds (group B) or the fixed injection rate was 4.0
      mL/sec (group C). Computed tomography (CT) at the L3 vertebral level was
      performed before and after contrast material injection. Aortic peak time, aortic
      peak enhancement, and period when aortic enhancement is 200 HU or greater (T200)
      were calculated. The Pearson product-moment correlation coefficient (r) was used
      to investigate relationships between patient weight and aortic peak time, aortic
      peak enhancement, and T200 in each group. RESULTS: A significant correlation
      between aortic peak time and patient weight (r = 0.91, P <.001) was observed in
      group C. No significant correlations between patient weight and aortic peak time
      were observed in group A (r = 0.16, P =.21) or B (r = -0.05, P =.69). A
      significant inverse correlation between aortic peak enhancement and patient
      weight (r = -0.70, P <.001) was observed in group C. No significant correlations
      between patient weight and aortic peak enhancement were observed in group A (r =
      0.09, P =.48) or B (r = 0.10, P =.41). A significant correlation between T200 and
      patient weight (r = 0.72, P <.001) was observed in group C. No significant
      correlations between patient weight and T200 were observed in group A (r = 0.12,
      P =.34) or B (r = 0.001, P =.99). CONCLUSION: Aortic peak time, aortic peak
      enhancement, and T200 were closely related to injection duration in the protocol
      with contrast material dose determined according to patient weight.

PMID- 14695391
TI  - Induction of diabetes in nonhuman primates by means of temporary arterial
      embolization and selective arterial injection of streptozotocin.
AB  - PURPOSE: To develop and assess a technique for induction of C peptide-negative
      diabetes in adult nonhuman primates in preparation for preclinical investigation
      of type 1 diabetes treatments. MATERIALS AND METHODS: First, temporary
      embolization of the hepatic and gastric arteries was performed in 14 adult
      nonhuman primates (six cynomolgus, five rhesus, and three pigtail macaques).
      After embolization was confirmed with angiography, streptozotocin was injected at
      a dose of 50-70 mg/kg into the celiac artery and branches supplying the pancreas.
      The macaques then were given intravenous injections of arginine and glucose, and
      blood levels of insulin and C peptide were measured with an enzyme-linked
      immunosorbent assay to determine whether diabetes had been induced. RESULTS: All
      but one of the macaques developed persistent long-term C peptide-negative
      diabetes after the streptozotocin injection. One macaque did not develop diabetes
      after the initial injection and was given a second dose of streoptozotocin, which
      did induce diabetes. None of the macaques showed any symptoms of hepatic or renal
      injury, and only one died (of gastric dilatation 5 days after the procedure).
      CONCLUSION: Streptozotocin injection after temporary embolization of the hepatic
      and gastric arteries is a safe and reproducible method for inducing C peptide
      negative diabetes in adult nonhuman primates in preparation for preclinical
      investigation of type 1 diabetes treatments.

PMID- 14695392
TI  - Radiofrequency ablation: modeling the enhanced temperature response to adjuvant
      NaCl pretreatment.
AB  - PURPOSE: To characterize the effects of volume and concentration of adjuvant NaCl
      pretreatment on radiofrequency (RF) ablation and to model these results to
      determine their applicability to in vivo systems. MATERIALS AND METHODS:
      Standardized 1-L 5% agar phantoms were constructed with central wells of varying
      volume that were filled with a protein-based polymer gel of varying NaCl
      concentration (0%-35%). RF ablation to the maximum system current output (2000
      mA) was applied to internally cooled 2-cm electrodes placed in the center of the
      gel wells. Remote thermometry was performed 20 mm from the electrode.
      Temperatures generated within the phantom were then used to model the response
      surface by using regression analysis. The generated model was then applied to
      previously published in vivo data to determine its applicability to a porcine
      liver tissue model. Statistical analyses included one-way analysis of variance to
      compare the temperatures reached with different NaCl concentrations and volumes
      with those reached without NaCl. In addition, modeled functions were evaluated
      for goodness of fit and the statistical significance of their coefficients.
      RESULTS: NaCl volume and concentration had significant effects on RF-generated
      heating of the agar phantoms. The mean maximum temperature, 91.4 degree C +/- 0.8
      (SD), was reached with 3.5 mL of 10% NaCl gel. This was significantly higher than
      the mean temperature reached in phantoms containing 0% NaCl gel, 40.3 degree C +/
      4.9 (P <.001). Heat increases to the maximum temperature correlated strongly
      with the deposited RF energy, with maximum temperatures limited by the current
      output of the RF generator. The response surface was defined by a generator
      energy-dependent region and a generator current-limited region, which were best
      modeled by a modified gamma-variate function and an exponential function,
      respectively (r2 = 0.92). This model correlated well with previously published in
      vivo data (r2 = 0.86). CONCLUSION: Modulation of electrical conductivity has
      different effects on RF ablation response that are dependent on generator
      capabilities and the volume and concentration of NaCl pretreatment.

PMID- 14695393
TI  - Contrast-enhanced MR delineation of stunned myocardium with administration of
      MnCl(2) in rats.
AB  - PURPOSE: To determine whether stunned myocardium can be delineated at magnetic
      resonance (MR) imaging with differential cellular uptake of manganese ions.
      MATERIALS AND METHODS: Twenty-one adult Sprague-Dawley rats underwent either (a)
      a sequence of three episodes of 10 minutes of coronary artery occlusion and 12
      minutes of reflow (group 1, n = 9); (b) a single episode of 10 minutes of
      occlusion followed by reflow (group 2, n = 6), designed to produce different
      degrees of myocardial stunning; or (c) a single episode of 2 minutes of occlusion
      followed by reperfusion (group 3, n = 6), designed to produce no stunning.
      Ventricular wall thickening was measured on spin-echo (SE) MR images. MnCl2
      (0.025 mmol/kg) was intravenously infused for 10 minutes. Highly T1-sensitive
      inversion-recovery (IR) SE images were obtained to detect subtle regional
      differences in manganese accumulation. Hearts were stained at sacrifice to define
      area at risk and to test for myocardial infarction. Significance of differences
      in mean values was evaluated with repeated-measures analysis of variance.
      RESULTS: All hearts were free of infarction, as detected with
      triphenyltetrazolium chloride staining. On IR SE images, the hearts from rats in
      groups 1 and 2 exhibited clearly delineated regions of diminished manganese
      uptake in the expected territory of the occluded artery. The circumferential
      extent of the manganese-defined defect (45.5% +/- 5.6) was similar to that of the
      area at risk (46.8% +/- 7.5). Systolic wall thickening in the defect was
      significantly (P <.01) less than in the nonischemic myocardium (2.7% +/- 3.3 vs
      31.2% +/- 7.5 and 10.0% +/- 4.8 vs 28.6% +/- 6.5, respectively, for groups 1 and
      2). The hearts from rats in group 3 demonstrated no wall thickening deficit or
      abnormal zone on manganese-enhanced images. CONCLUSION: Stunned myocardium was
      delineated with MnCl2-enhanced MR imaging as a hypoenhanced zone. This finding
      suggests that Ca2+ channel activity is diminished in stunned myocardium.

PMID- 14695394
TI  - Influence of body size and section level on calcium phantom measurements at
      coronary artery calcium CT scanning.
AB  - PURPOSE: To determine whether differences in body mass index (BMI) and image
      section levels representing the proximal through the distal sections of the heart
      are associated with attenuation differences in images of calcium phantoms scanned
      during computed tomographic (CT) imaging of study subjects. MATERIALS AND
      METHODS: Mean attenuation values for three calcium phantoms (each with a
      different calcium hydroxyapatite concentration), as measured at each of four
      different image section levels, were obtained for 691 participants in the
      Muscatine CT Vascular Calcium Study. The subjects were grouped according to sex
      specific BMI quartiles, and the degree of attenuation in each phantom was
      investigated as a function of image section level and BMI quartile. Spearman rank
      order correlation coefficients and one-, two-, and three-factor repeated-measures
      analysis of variance were used to examine the association between section level
      and BMI and the mean phantom attenuations. RESULTS: Attenuation was, for the most
      part, significantly associated with both section level (P <.005) and BMI quartile
      (P <.0025-.05). The degree of attenuation tended to decrease in images obtained
      at the more distal cardiac levels and to increase with increasing BMI quartile.
      CONCLUSION: Differences in attenuation related to BMI and image section level
      appear to have a significant effect on current calcium scoring methods.

PMID- 14695395
TI  - Cost-effectiveness of uterine artery embolization and hysterectomy for uterine
      fibroids.
AB  - PURPOSE: To compare the cost-effectiveness of uterine artery embolization (UAE)
      with that of hysterectomy for women with symptomatic uterine fibroids. MATERIALS
      AND METHODS: The authors developed a decision model to compare the costs and
      effectiveness of UAE and hysterectomy. In the model, a cohort of women aged 40
      years with a diagnosis of uterine fibroids and no desire for future pregnancy was
      followed up until menopause. The analysis was performed from a societal
      perspective, including all costs and effects, regardless of who incurs them.
      Transition probability and quality-of-life estimates were obtained from the
      literature and a gynecologist, whereas costs (in 1999 U.S. dollars) were
      estimated by using rates of Medicare reimbursement for hospital costs and
      physician fees. Sensitivity analyses of key estimates were performed. Results
      were expressed in costs per quality-adjusted life-year (QALY). RESULTS: UAE was
      more effective (8.29 vs 8.18 QALYs) and less expensive (US dollars 6916 vs US
      dollars 7847) than hysterectomy. Cost-effectiveness results, with the exception
      of quality-of-life data, were robust to changes in most model assumptions. When
      the quality-of-life adjustment was eliminated, the two procedures were equally
      effective. CONCLUSION: UAE is a cost-effective alternative to hysterectomy across
      a wide range of assumptions about the costs and effectiveness of the two
      procedures. However, the study results were sensitive to changes in quality-of
      life values.

PMID- 14695396
TI  - Prostate cancer localization with endorectal MR imaging and MR spectroscopic
      imaging: effect of clinical data on reader accuracy.
AB  - PURPOSE: To determine the effect of digital rectal examination findings, sextant
      biopsy results, and prostate-specific antigen (PSA) levels on reader accuracy in
      the localization of prostate cancer with endorectal magnetic resonance (MR)
      imaging and MR spectroscopic imaging. MATERIALS AND METHODS: This was a
      retrospective study of 37 patients (mean age, 57 years) with biopsy-proved
      prostate cancer. Transverse T1-weighted, transverse high-spatial-resolution, and
      coronal T2-weighted MR images and MR spectroscopic images were obtained. Two
      independent readers, unaware of clinical data, recorded the size and location of
      suspicious peripheral zone tumor nodules on a standardized diagram of the
      prostate. Readers also recorded their degree of diagnostic confidence for each
      nodule on a five-point scale. Both readers repeated this interpretation with
      knowledge of rectal examination findings, sextant biopsy results, and PSA level.
      Step-section histopathologic findings were the reference standard. Logistic
      regression analysis with generalized estimating equations was used to correlate
      tumor detection with clinical data, and alternative free-response receiver
      operating characteristic (AFROC) curve analysis was used to examine the overall
      effect of clinical data on all positive results. RESULTS: Fifty-one peripheral
      zone tumor nodules were identified at histopathologic evaluation. Logistic
      regression analysis showed awareness of clinical data significantly improved
      tumor detection rate (P <.02) from 15 to 19 nodules for reader 1 and from 13 to
      19 nodules for reader 2 (27%-37% overall) by using both size and location
      criteria. AFROC analysis showed no significant change in overall reader
      performance because there was an associated increase in the number of false
      positive findings with awareness of clinical data, from 11 to 21 for reader 1 and
      from 16 to 25 for reader 2. CONCLUSION: Awareness of clinical data significantly
      improves reader detection of prostate cancer nodules with endorectal MR imaging
      and MR spectroscopic imaging, but there is no overall change in reader accuracy,
      because of an associated increase in false-positive findings. A stricter
      definition of a true-positive result is associated with reduced sensitivity for
      prostate cancer nodule detection.

PMID- 14695398
TI  - Case 66: caudal regression syndrome in the fetus of a diabetic mother.

PMID- 14695399
TI  - Full-thickness and partial-thickness supraspinatus tendon tears: value of US
      signs in diagnosis.
AB  - PURPOSE: To determine which US signs are important in the diagnosis of a
      surgically identifiable supraspinatus tendon tear. MATERIALS AND METHODS: Fifty
      consecutive ultrasonographic (US) studies of the shoulder in patients who
      underwent arthroscopic follow-up were retrospectively reviewed by a
      musculoskeletal radiologist. US images of the supraspinatus tendon were evaluated
      for tendon nonvisualization, abnormal tendon echogenicity, tendon thinning,
      greater tuberosity cortical irregularity, cartilage interface sign, joint fluid,
      and subacromial-subdeltoid bursal fluid. US findings were compared with
      arthroscopic results. Sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy were calculated for each US sign in the
      diagnosis of full-thickness tendon tear and again for any type of supraspinatus
      tendon tear. RESULTS: Arthroscopy revealed 21 full-thickness tears, five bursal
      surface partial-thickness tears, 10 articular surface partial-thickness tears,
      and 14 patients without tear of the supraspinatus tendon. The presence of greater
      tuberosity cortical irregularity and joint fluid was most important in the
      diagnosis of full-thickness supraspinatus tendon tear (sensitivity, 60%;
      specificity, 100%; positive predictive value, 100%; negative predictive value,
      78%; accuracy, 84%). For diagnosis of any type of supraspinatus tendon tear
      (partial or full thickness), tendon nonvisualization, greater tuberosity cortical
      irregularity, and cartilage interface sign are most important, although a
      combination of signs did not improve accuracy. CONCLUSION: Secondary US signs,
      such as greater tuberosity cortical irregularity and joint fluid, are most
      valuable in the diagnosis of supraspinatus tendon tear.

PMID- 14695400
TI  - Improved detection of focal liver lesions at MR imaging: multicenter comparison
      of gadoxetic acid-enhanced MR images with intraoperative findings.
AB  - PURPOSE: To evaluate the safety and efficacy of gadoxetic acid disodium-enhanced
      magnetic resonance (MR) imaging for the detection of focal liver lesions, with
      results of histopathologic examination and/or intraoperative ultrasonography used
      as a standard of reference. MATERIALS AND METHODS: One hundred sixty-nine
      patients who were known to have or suspected of having focal liver lesions and
      were scheduled for liver surgery were included in this study. Results in 131
      patients could be included in the efficacy analysis. MR imaging was performed
      before and immediately and 20 minutes after bolus injection of 0.025 mmol/kg of
      the liver-specific hepatobiliary contrast agent gadoxetic acid. T1-weighted
      gradient-echo (with and without fat saturation and including dynamic data sets)
      and T2-weighted fast spin-echo/turbo spin-echo sequences were performed. All
      images were evaluated on site and by three independent and blinded off-site
      reviewers. Lesion matching based on the standard-of-reference results was
      performed. Differences in lesion detection with precontrast and with postcontrast
      MR images were assessed with the two-sided Wilcoxon signed rank test. RESULTS:
      Gadoxetic acid was well tolerated. In the on-site review, the number of patients
      in whom all lesions were correctly matched increased from 89 of 129 patients at
      precontrast MR imaging to 103 of 129 patients at postcontrast MR imaging. In the
      off-site evaluation, the number of patients in whom all lesions were correctly
      matched and the corresponding sensitivity values increased from 72 (55.8%), 68
      (52.7%), and 66 (51.2%) with the precontrast images to 88 (68.2%), 69 (53.5%),
      and 76 (58.9%) with the postcontrast images for readers 1, 2, and 3,
      respectively. Two of the three blinded readers showed a statistically significant
      difference in lesion detection between precontrast and postcontrast MR imaging (P
      <.001 and P =.008). A large number of additionally correctly detected and
      localized lesions were smaller than 1 cm. CONCLUSION: MR imaging with gadoxetic
      acid is safe and improves lesion detection and localization.

PMID- 14695401
TI  - Macrovesicular hepatic steatosis in living related liver donors: correlation
      between CT and histologic findings.
AB  - PURPOSE: To assess degree of macrovesicular steatosis with unenhanced computed
      tomography (CT) and correlate it with histologic findings in potential donors for
      living related liver transplantation. MATERIALS AND METHODS: Forty-two candidates
      underwent unenhanced CT within 4 weeks of core liver biopsy. An experienced liver
      pathologist, blinded to both CT and surgical findings, retrospectively reviewed
      biopsy specimens and determined degree of macrovesicular steatosis. A radiologist
      blinded to histologic grading calculated mean hepatic attenuation in each donor
      liver by averaging 25 region-of-interest (ROI) measurements on five sections
      (five ROIs per section). Mean splenic attenuation was calculated with three
      separate ROI measurements. Liver attenuation index (LAI) was derived and defined
      as the difference between mean hepatic and mean splenic attenuation. Body mass
      index (BMI) was determined for each patient. Linear regression analysis was used
      to correlate degree of macrovesicular steatosis with both LAI and BMI. RESULTS:
      LAI correctly predicted degree of macrovesicular steatosis in 38 (90%) of 42
      cases. In four of four livers, LAI below -10 HU correlated with greater than 30%
      macrovesicular steatosis (unacceptable for liver transplantation). In nine of 11
      livers, LAI was between -10 and 5 HU and correctly predicted 6%-30% steatosis
      (relative contraindication). In two of 11 cases, LAI overestimated degree of
      hepatic steatosis. LAI above 5 HU correctly predicted 0%-5% steatosis in 25 of 27
      livers. In two of 27 cases, parenchymal hemosiderin deposition led to an increase
      in LAI into the normal range, despite mild histologically confirmed steatosis.
      Degree of histologic macrovesicular steatosis correlated well with LAI (r = 0.92)
      and marginally with BMI (r = 0.45). Of 27 potential donors with normal livers at
      CT and acceptable LAI levels, four (15%) were deemed poor donor candidates
      because core biopsy revealed subtle hepatic necrosis and nonspecific hepatitis.
      CONCLUSION: Although unenhanced CT quantifies the degree of macrovesicular
      steatosis relatively well, it may preclude a liver biopsy only in a small
      percentage of potential donors with low LAI (unacceptable degree of steatosis).
      Core liver biopsy is still necessary in the majority of donors with normal LAI to
      identify those with both fatty liver and coexistent hemosiderin deposition or
      radiologically occult diffuse liver diseases.

PMID- 14695402
TI  - Hepatocellular carcinoma: regional therapy with a magnetic targeted carrier bound
      to doxorubicin in a dual MR imaging/ conventional angiography suite--initial
      experience with four patients.
AB  - Four patients with inoperable hepatocellular carcinoma were treated with a
      magnetic targeted carrier bound to doxorubicin (MTC-DOX) by using a joint
      magnetic resonance (MR) imaging/conventional angiography system consisting of a
      1.5-T short-bore magnet connected to a C-arm angiography unit by a sliding
      tabletop. Selective transcatheter delivery of the MTC-DOX to the hepatic artery
      was monitored by using intraprocedural MR imaging, and interim catheter
      manipulation was performed with fluoroscopic guidance to optimize agent delivery
      to the tumor and minimize delivery to normal tissue. The final fraction of
      treated tumor volume ranged from 0.64 to 0.91. The fraction of affected normal
      liver volume ranged from 0.07 to 0.30. The dual MR imaging/conventional
      angiography system shows promise for directing magnetically targeted tumor
      therapies.

PMID- 14695403
TI  - Delayed helical CT acquisition in the detection of endoleak.

PMID- 14695404
TI  - Unresectable hepatocellular carcinoma: meta-analysis of arterial embolization.

PMID- 14695405
TI  - Animal subjects in radiation therapy experiments.

PMID- 14695406
TI  - A new insight into the formation of osteolytic lesions in multiple myeloma.

PMID- 14695407
TI  - Sweet success--a treatment for McArdle's disease.

PMID- 14695408
TI  - The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic
      lesions in multiple myeloma.
AB  - BACKGROUND: Myeloma cells may secrete factors that affect the function of
      osteoblasts, osteoclasts, or both. METHODS: We subjected purified plasma cells
      from the bone marrow of patients with newly diagnosed multiple myeloma and
      control subjects to oligonucleotide microarray profiling and biochemical and
      immunohistochemical analyses to identify molecular determinants of osteolytic
      lesions. RESULTS: We studied 45 control subjects, 36 patients with multiple
      myeloma in whom focal lesions of bone could not be detected by magnetic resonance
      imaging (MRI), and 137 patients in whom MRI detected such lesions. Different
      patterns of expression of 57 of approximately 10,000 genes from purified myeloma
      cells could be used to distinguish the two groups of patients (P<0.001).
      Permutation analysis, which adjusts the significance level to account for
      multiple comparisons in the data sets, showed that 4 of these 57 genes were
      significantly overexpressed by plasma cells from patients with focal lesions. One
      of these genes, dickkopf 1 (DKK1), and its corresponding protein (DKK1) were
      studied in detail because DKK1 is a secreted factor that has been linked to the
      function of osteoblasts. Immunohistochemical analysis of bone marrow-biopsy
      specimens showed that only myeloma cells contained detectable DKK1. Elevated DKK1
      levels in bone marrow plasma and peripheral blood from patients with multiple
      myeloma correlated with the gene-expression patterns of DKK1 and were associated
      with the presence of focal bone lesions. Recombinant human DKK1 or bone marrow
      serum containing an elevated level of DKK1 inhibited the differentiation of
      osteoblast precursor cells in vitro. CONCLUSIONS: The production of DKK1, an
      inhibitor of osteoblast differentiation, by myeloma cells is associated with the
      presence of lytic bone lesions in patients with multiple myeloma.

PMID- 14695409
TI  - Single versus double autologous stem-cell transplantation for multiple myeloma.
AB  - BACKGROUND: We conducted a randomized trial of the treatment of multiple myeloma
      with high-dose chemotherapy followed by either one or two successive autologous
      stem-cell transplantations. METHODS: At the time of diagnosis, 399 previously
      untreated patients under the age of 60 years were randomly assigned to receive a
      single or double transplant. RESULTS: A complete or a very good partial response
      was achieved by 42 percent of patients in the single-transplant group and 50
      percent of patients in the double-transplant group (P=0.10). The probability of
      surviving event-free for seven years after the diagnosis was 10 percent in the
      single-transplant group and 20 percent in the double-transplant group (P=0.03).
      The estimated overall seven-year survival rate was 21 percent in the single
      transplant group and 42 percent in the double-transplant group (P=0.01). Among
      patients who did not have a very good partial response within three months after
      one transplantation, the probability of surviving seven years was 11 percent in
      the single-transplant group and 43 percent in the double-transplant group
      (P<0.001). Four factors were significantly related to survival: base-line serum
      levels of beta2-microglobulin (P<0.01) and lactate dehydrogenase (P<0.01), age
      (P<0.05), and treatment group (P<0.01). CONCLUSIONS: As compared with a single
      autologous stem-cell transplantation after high-dose chemotherapy, double
      transplantation improves overall survival among patients with myeloma, especially
      those who do not have a very good partial response after undergoing one
      transplantation.

PMID- 14695410
TI  - The effect of oral sucrose on exercise tolerance in patients with McArdle's
      disease.
AB  - BACKGROUND: Energy metabolism in muscles relies predominantly on the breakdown of
      glycogen early in exercise. In patients with McArdle's disease, blocked
      glycogenolysis in muscles results in low exercise tolerance and can lead to
      muscle injury, particularly in the first minutes of exercise. We hypothesized
      that ingesting sucrose before exercise would increase the availability of glucose
      and would therefore improve exercise tolerance in patients with McArdle's
      disease. METHODS: In a single-blind, randomized, placebo-controlled crossover
      study, 12 patients with McArdle's disease drank 660 ml of a beverage that had
      been sweetened with artificial sweeteners (placebo) or with 75 g of sucrose after
      an overnight fast. Thirty to 40 minutes later, the patients rode a stationary
      bicycle at a constant workload for 15 minutes while the heart rate, level of
      perceived exertion, and venous blood glucose levels were monitored. RESULTS:
      Supplemental sucrose increased the mean plasma glucose level by more than 36 mg
      per deciliter (2.0 mmol per liter) and resulted in a marked improvement in
      exercise tolerance in all patients. The mean (+/-SE) heart rate dropped by a
      maximum of 34+/-3 beats per minute (P<0.001), and the level of perceived exertion
      fell dramatically when the patients ingested glucose as compared with when they
      received the placebo. CONCLUSIONS: This study suggests that the ingestion of
      sucrose before exercise can markedly improve exercise tolerance in patients with
      McArdle's disease. The treatment takes effect during the time when muscle injury
      commonly develops in these patients. In addition to increasing the patients'
      exercise capacity and sense of well-being, the treatment may protect against
      exercise-induced rhabdomyolysis.

PMID- 14695411
TI  - The Canadian C-spine rule versus the NEXUS low-risk criteria in patients with
      trauma.
AB  - BACKGROUND: The Canadian C-Spine (cervical-spine) Rule (CCR) and the National
      Emergency X-Radiography Utilization Study (NEXUS) Low-Risk Criteria (NLC) are
      decision rules to guide the use of cervical-spine radiography in patients with
      trauma. It is unclear how the two decision rules compare in terms of clinical
      performance. METHODS: We conducted a prospective cohort study in nine Canadian
      emergency departments comparing the CCR and NLC as applied to alert patients with
      trauma who were in stable condition. The CCR and NLC were interpreted by 394
      physicians for patients before radiography. RESULTS: Among the 8283 patients, 169
      (2.0 percent) had clinically important cervical-spine injuries. In 845 (10.2
      percent) of the patients, physicians did not evaluate range of motion as required
      by the CCR algorithm. In analyses that excluded these indeterminate cases, the
      CCR was more sensitive than the NLC (99.4 percent vs. 90.7 percent, P<0.001) and
      more specific (45.1 percent vs. 36.8 percent, P<0.001) for injury, and its use
      would have resulted in lower radiography rates (55.9 percent vs. 66.6 percent,
      P<0.001). In secondary analyses that included all patients, the sensitivity and
      specificity of CCR, assuming that the indeterminate cases were all positive, were
      99.4 percent and 40.4 percent, respectively (P<0.001 for both comparisons with
      the NLC). Assuming that the CCR was negative for all indeterminate cases, these
      rates were 95.3 percent (P=0.09 for the comparison with the NLC) and 50.7 percent
      (P=0.001). The CCR would have missed 1 patient and the NLC would have missed 16
      patients with important injuries. CONCLUSIONS: For alert patients with trauma who
      are in stable condition, the CCR is superior to the NLC with respect to
      sensitivity and specificity for cervical-spine injury, and its use would result
      in reduced rates of radiography.

PMID- 14695412
TI  - Body packing--the internal concealment of illicit drugs.

PMID- 14695413
TI  - Pulmonary alveolar proteinosis.

PMID- 14695414
TI  - Images in clinical medicine. Anterior cervical osteophytes causing airway
      compromise.

PMID- 14695415
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 40-2003. A 14-month-old boy with recurrent abdominal distention
      and diarrhea.

PMID- 14695416
TI  - Multiple myeloma, 2004--one or two transplants?

PMID- 14695417
TI  - Choosing between clinical prediction rules.

PMID- 14695418
TI  - Systematic identification of drugs that cause birth defects--a new opportunity.

PMID- 14695419
TI  - Putting the brakes on insulin signaling.

PMID- 14695420
TI  - Chronic renal failure after transplantation of a nonrenal organ.

PMID- 14695421
TI  - Withdrawal of mechanical ventilation.

PMID- 14695422
TI  - Office-based treatment of opiate addiction.

PMID- 14695423
TI  - Warfarin prophylaxis in the antiphospholipid antibody syndrome.

PMID- 14695424
TI  - An EBV-positive lymphoproliferative disorder after therapy with alemtuzumab.

PMID- 14695425
TI  - Gentamicin and CFTR.

PMID- 14695426
TI  - Pure red-cell aplasia secondary to antierythropoietin antibodies.

PMID- 14695427
TI  - Images in clinical medicine. Emphysematous pancreatitis.

PMID- 14695428
TI  - AIDS-related opportunistic infections in Hospital Kuala Lumpur.
AB  - We retrospectively reviewed 419 HIV/AIDS patients in Hospital Kuala Lumpur from
      1994 to 2001. In the male group, the age range was 20-74, with a mean age 37
      years, while in the female group it was 17-63, with a mean age of 33 years. With
      regard to age group, it was found that the preponderant age group was 25-34
      years. The majority of male subjects were Chinese (52.5%), single (56.3%), and
      unemployed (55.1%), whereas the females were Malay (42.3%), married (79.5%), and
      non-laborer (64.1%). Also, both groups resided in Kuala Lumpur and had
      heterosexual contact as the leading cause of HIV transmission. More than half of
      the patients had CD4 cell counts of <200 cells/cumm. We found that the
      acquisition of HIV infection via intravenous drug use (IDU) was directly related
      to the incidence of tuberculosis infection (P < 0.05). Further analysis showed
      HIV-related tuberculosis with IDU was also dependently correlated with
      occupational status (unemployed) (P < 0.05). The four main AIDS-defining diseases
      include tuberculosis (48%), Pneumocystis carinii pneumonia (13%), toxoplasmic
      encephalitis (11%), and cryptococcal meningitis (7%); in addition, 53% of these
      patients were found to have CD4 cell counts of less than 200 cells/cumm at the
      time of diagnosis.

PMID- 14695429
TI  - Encephalitis in Taiwan: a prospective hospital-based study.
AB  - To investigate encephalitis in Taiwan, a multicenter study was conducted with
      patients who had acute severe neurological dysfunction and suspected encephalitis
      from May 2000 to December 2001. Demographic data such as age, sex, and seasons
      were analyzed. Polymerase chain reaction analyses were performed to determine the
      microbiologic diagnosis. The patients included 73 males and 54 females, with a
      peak age of 10-40 years old. Microbiologic diagnoses in 86 (69%) of 124 cases
      involved herpes simplex virus (HSV, 45 cases), varicella zoster (16 cases),
      Mycobacterium tuberculosis (10 cases), cytomegalovirus (8 cases), adenovirus (5
      cases), influenza (1 case), and enterovirus (1 case). Pathogens were found in 69%
      of the cases. Encephalitis was most likely to occur in June and July. Based on
      the results, HSV is still the major viral cause of encephalitis in Taiwan.

PMID- 14695430
TI  - Evaluation of automated ribotyping system for characterization and identification
      of verocytotoxin-producing Escherichia coli isolated in Japan.
AB  - The usefulness of an automated ribotyping system (RiboPrinter) was evaluated for
      characterizing and identifying clinical isolates of 37 verocytotoxin-producing
      Escherichia coli (VTEC) strains and 16 non-VTEC strains. All strains were
      successfully ribotyped with satisfactory reproducibility and stability and
      characterized into 10 different ribogroups. All VTEC O157 strains were
      characterized into a specific ribogroup and correctly typed into the specific
      DuPont ID for VTEC O157:H7, while all of the non-VTEC O157 strains were clearly
      distinguished from VTEC O157. VTEC O26 and O111 strains, the most prevalent VTEC
      serotypes after O157, were also well characterized into specific ribogroups and
      identified. These results suggest that the RiboPrinter may have an advantage over
      other typing systems in that it can rapidly and easily discriminate VTEC from non
      VTEC strains of the most prevalent VTEC serotypes in Japan, even though it
      provides a lesser degree of discrimination than pulsed-field gel electrophoresis
      (PFGE). With a hierarchical or sequential typing combining the RiboPrinter and
      PFGE, rapid and accurate typing can be achieved during an outbreak of VTEC, which
      may be useful in clinical and public health settings.

PMID- 14695431
TI  - Evaluation of RT-PCR as a tool for diagnosis of secondary dengue virus infection.
AB  - Dengue fever and dengue hemorrhagic fever are serious illnesses in many tropical
      and subtropical countries. Laboratory tests are essential for the confirmation of
      dengue virus infection. In the present study, we examined the reliability of
      reverse transcriptase polymerase chain reaction (RT-PCR) in the laboratory
      diagnosis of dengue, especially in secondary dengue virus infections. We defined
      the day when fever subsided as fever day 0. In primary dengue virus infection,
      the dengue viral genome was detected in all of the 7 samples which were collected
      on fever day -1 or earlier, in 3 of 4 samples on fever day 0, and in 1 of 2
      samples on fever day 1. None of the samples collected on fever day 2 or later
      were positive by RT-PCR. In secondary dengue virus infection, the dengue viral
      genome was detected in all of the 28 samples which were collected on fever day -2
      or earlier, in 25 of 26 on fever day -1, in 29 of 34 on fever day 0, and in 5 of
      10 on fever days 1-2. None of the samples collected on fever day 3 or later were
      positive. Virus isolation and direct titration were attempted using the plasma
      samples. When the data of secondary infection cases were analyzed based on fever
      day, dengue viruses were isolated from all of the 5 samples which were collected
      on fever day -2 or earlier, in 5 of 13 samples on fever day -1, and in 4 of 22 on
      fever day 0, but were not isolated from any of the 4 samples collected on fever
      days 1-2. Viruses were directly detected in 7 of 11 samples on fever day -2 or
      earlier, in 4 of 13 on fever day -1, and in 1 of 16 on fever day 0. These results
      indicate that RT-PCR is more sensitive than virus isolation and direct virus
      titration for determining secondary dengue virus infection. The results also
      suggest that RT-PCR is a useful diagnostic test for confirmation of dengue virus
      infection in secondary infection as well as in primary infection, especially when
      plasma samples are collected before the fever subsides.

PMID- 14695432
TI  - Ofloxacin minimum inhibitory concentration versus disk diffusion zone diameter
      for Salmonella enterica serovar Typhi isolates: problems in the detection of
      ofloxacin resistance.
AB  - Using the guidelines of the National Committee for Clinical Laboratory Standards
      (NCCLS), a total of 421 blood culture isolates of Salmonella enterica serovar
      Typhi obtained during 1991-2001 were tested for susceptibility to ofloxacin (OFX)
      by the disc diffusion method, and for the determination of minimum inhibitory
      concentration (MIC) values of OFX by the agar dilution method. Among 421
      isolates, 248 were fully OFX-sensitive showing MICs of 0.0125-0.075 microg/ml and
      inhibitory zone diameters of > or =24 mm. The remaining 173 isolates (MICs of 0.5
      1.5 microg/ml) that were treated with OFX did not respond to the therapy.
      However, 169 (97.69%) of the 173 isolates were determined to be susceptible (zone
      diameter > or =16 mm) by the disc diffusion method, whereas only 3 were
      intermediately susceptible (zone diameter 13-15 mm) and the final isolate showed
      OFX-resistance (zone diameter 12 mm). Thus, following the NCCLS guidelines, OFX
      resistance in S. enterica serovar Typhi was not detected by the disc diffusion
      test. The present data suggest a revision of the NCCLS breakpoints in selecting
      OFX as the preferred treatment regimen for S. enterica serovar Typhi

PMID- 14695433
TI  - Age-specific mumps seroprevalence of an unvaccinated population of adolescents in
      Ankara, Turkey.
AB  - This study aimed to detect the age-specific mumps seroprevalence of an
      unvaccinated population of adolescents in Ankara, Turkey and to compare the
      prevaccination epidemiology of mumps with those of some other countries. Four
      hundred and forty adolescents (227 females, 213 males) aged 9 - 16 years who were
      admitted to the Adolescent Unit were included in this study. For each
      participant, a questionnaire was completed and mumps-specific IgG antibodies were
      screened quantitatively by enzyme-linked fluorescent assay. Of the 440 patients
      screened for mumps antibodies, 48 (10.9%) were seronegative. Mumps seronegativity
      according to sex and age groups were 13.6, 9.9, and 10.4% in females and 18,
      10.2, and 6.2% in males in the age groups of 9 - 10, 11 - 13, and 14 - 16,
      respectively. Mumps immunization models similar to those of European countries
      might be acceptable for Turkey, but since a low vaccination coverage may shift
      mumps infection to older ages, mumps immunization of adolescents is important
      until a national mumps vaccination program with a high coverage could be
      sustained. The routine health supervision visit at ages 11 to 12 years is an
      ideal time to immunize unvaccinated adolescents.

PMID- 14695434
TI  - Chromosomal transferable multidrug resistance genes of Salmonella enterica
      serovar infantis.

PMID- 14695435
TI  - Surveillance of poliovirus-isolates in Japan, 2002.

PMID- 14695436
TI  - Emerging and reemerging infections in China 2002-2003: a comment.

PMID- 14695437
TI  - Atypical proteinase K-resistant prion protein (PrPres) observed in an apparently
      healthy 23-month-old Holstein steer.

PMID- 14695438
TI  - Characterization and localization of fluorescent Pseudomonas cold shock
      protein(s) by monospecific polyclonal antibodies.
AB  - Cold shock protein (CSP) from Pseudomonas fluorescens MTCC 103 and cold resistant
      protein (CRP) from its mutant CRPF8 of 14 and 35 kd, respectively were purified
      to homogeneity by HPLC. Polyclonal antibodies were raised against these proteins
      and the expression level was checked at different temperatures, i.e., 4, 10, 20,
      30 and 37 C. Furthermore, morphological changes in P. fluorescens MTCC 103 and
      its mutant (CRPF8) were analyzed by transmission electron microscopy (TEM).
      Localization of CSP and CRP documented with immunoelectron microscopy, using
      colloidal gold particles conjugated with secondary antibodies being the probe
      were used. Nevertheless, the results of cytosolic localization of CSP and CRP
      were evident. Furthermore, the expression of CSP and CRP increased with decrease
      in temperature and the cell wall thickness of the mutant exhibited 2-fold
      increase, thus facilitating low temperature survival.

PMID- 14695439
TI  - Molecular epidemiology of Bordetella pertussis isolated in Taiwan, 1992-1997.
AB  - In Taiwan, the number of pertussis cases including various types of infection has
      been increasing in recent years, especially in 1997. Since 71% of the reported
      cases concentrated in the densely populated Taipei metropolitan area, concerns
      have been raised that a highly contagious strain of Bordetella pertussis might
      have appeared in Taipei. In this study, 114 strains of B. pertussis including
      those isolated in 1992-1996 (n = 53) and 1997 (n = 61) were subjected to pulsed
      field gel electrophoresis (PFGE) of the Xba I digests from their chromosomes.
      Based on the band patterns, they were divided into 21 subtypes, P1 to P21. The
      strains isolated in 1997 consist of 17 subtypes including 9 new subtypes which
      did not appear in the previous years, indicating that the outbreaks in 1997 were
      not caused by a sole specific virulent strain. Dendrogram analysis indicated that
      the 21 subtypes can be grouped into five clusters, with the first four subtypes
      possessing 60 to 95% relatedness to one another, whereas relatedness between
      cluster 5 (containing P21 only) and the other clusters is less than 50%. Notably,
      all the subtypes except P12 and P21 appeared at least once in Taipei and the
      majority of the strains (54%) belong to two clusters, 3 and 4. These results
      suggest that highly dense population may facilitate spread and accelerate genetic
      divergence of this pathogen. This is the first report on pertussis molecular
      epidemiology in Taiwan.

PMID- 14695440
TI  - In vivo safety assessment of two Bifidobacterium longum strains.
AB  - Bifidobacteria are important members of the intestinal microbiota and are
      considered to contribute to maintaining health. However, the level of
      bifidobacteria colonising the intestine of elderly subjects tends to be lower
      than in younger adults. Therefore, two Bifidobacterium longum strains, isolated
      from healthy elderly, were chosen for supplementation of the endogenous
      Bifidobacterium microbiota in the elderly. Bifidobacteria are generally regarded
      safe for human consumption. However, since the strains are intended for
      consumption by the elderly, whom may be more prone to disease, it is important to
      ascertain their safety. For this purpose, the strains were given to healthy adult
      volunteers. No side effects were reported and no undesirable changes observed in
      the immune parameters measured. Based on this study it appears that the two
      strains are well tolerated by human subjects and there are no reservations about
      their food use.

PMID- 14695441
TI  - Need to differentiate lethal toxin-producing strains of Burkholderia gladioli,
      which cause severe food poisoning: description of B. gladioli pathovar
      cocovenenans and an emended description of B. gladioli.
AB  - Burkholderia cocovenenans produces a lethal toxin (Bongkrekic acid) that leads to
      high fatality in food poisoning cases. However, B. cocovenenans was combined in
      Burkholderia gladioli in 1999. B. gladioli was originally described as a
      phytopathogenic bacteria that sometimes causes pneumonia in humans and that acts
      as an opportunistic pathogen. We thought that it was clinically dangerous to
      describe these two species without considering their pathogenicities. From our
      data of 16S rRNA sequence analysis, DNA-DNA hybridization, and fatty acid
      analysis, we could confirm that B. cocovenenans and B. gladioli should be
      categorized as a single species. However the species really weaved lethal toxin
      producing strains with non-lethal strains. To emphasize that B. gladioli contains
      two different pathogens, we describe a new pathovar, B. gladioli pathovar
      cocovenenans, for the lethal toxin-producing strains. We provide characteristics
      that differentiate this lethal toxin-producing pathovar from other
      phytopathogenic pathovars within B. gladioli, together with an emended
      description of B. gladioli.

PMID- 14695442
TI  - Moenomycin-resistance is associated with vancomycin-intermediate susceptibility
      in Staphylococcus aureus.
AB  - We have previously isolated a vancomycin-intermediate susceptibility mutant from
      methicillinresistant Staphylococcus aureus(MRSA) strain COL, and demonstrated the
      increased glycan-chain length and the decreased moenomycin-susceptibility. To
      further investigate the relationship between the resistance to vancomycin and to
      moenomycin, we isolated moenomycin-resistant mutants (4-16 fold higher compared
      to the parent) from 5 MRSA and 2 methicillin-sensitive S. aureus(MSSA) strains.
      The MRSA mutants showed a decreased susceptibility to vancomycin (2-4 fold),
      teicoplanin (2-4 fold) and an increased susceptibility to methicillin (2-8 fold).
      MSSA strains also showed similar results with those of MRSA strains except that
      there was no alteration of methicillin susceptibility. Among the mutants, three
      mutants including two MRSA mutants and one MSSA mutant were analyzed by electron
      microscopy, and they showed thickened cell walls compared to those of the
      parents. The glycan-chain length of the peptidoglycan of the mutant was shown to
      be slightly longer than that of the parent, but the muropeptide profile was very
      similar. The expression levels of all PBPs were similar to those of the parent.
      Furthermore, the nucleotide sequences of sgtA, sgtB and pbp2 in the mutant were
      identical to those of the parent. These results indicate that the moenomycin
      resistance is closely associated with vancomycin-intermediate susceptibility in
      S. aureus.

PMID- 14695443
TI  - Molecular cloning and characterization of the HmrM multidrug efflux pump from
      Haemophilus influenzae Rd.
AB  - We cloned a gene responsible for norfloxacin resistance from the chromosomal DNA
      of Haemophilus influenzae Rd, and designated the gene as hmrM. HmrM showed
      sequence similarity with NorM of Vibrio parahaemolyticus and YdhE of Escherichia
      coli and others that belong to the MATE family multidrug efflux pumps. The
      recombinant plasmid carrying the hmrM gene conferred elevated resistance not only
      to norfloxacin but also to acriflavine, 4 ', 6-diamidino-2-phenylindole,
      doxorubicin, ethidium bromide, tetraphenylphosphonium chloride, Hoechst 33342,
      daunomycin, berberine, and sodium deoxycholate in Escherichia coli KAM32, a drug
      hypersensitive strain. We observed an Na+-dependent efflux of ethidium and an
      ethidium-induced efflux of Na+ in E. coli KAM32 cells harboring the plasmid
      carrying the hmrM gene. These results indicate that HmrM is an Na+/drug
      antiporter-type multidrug efflux pump. A difference in substrate preference was
      observed between HmrM, NorM, and YdhE.

PMID- 14695444
TI  - The basidiomycetous yeasts Cryptococcus diffluens and C. liquefaciens colonize
      the skin of patients with atopic dermatitis.
AB  - Our previous research showed that lipophilic yeasts, Malassezia species, colonize
      the skin of patients with atopic dermatitis (AD) at a high frequency. In this
      study, we found that two basidiomycetous yeasts, Cryptococcus diffluens and C.
      liquefaciens, colonize the skin significantly more frequently in AD patients than
      in healthy subjects. Transparent dressings were applied to the skin of 36 AD
      patients and 30 healthy subjects and then transferred onto Sabouraud dextrose
      agar. Colonies recovered from the medium were identified by DNA sequence analysis
      of internal transcribed spacer regions and the D1/D2 26S rRNA gene. C. diffluens
      and C. liquefaciens were isolated from 42% (15/36) and 33% (12/36) of AD patients
      and from 20% (6/30) and 20% (6/30) of healthy subjects, respectively. In
      addition, fungal DNA was extracted directly from the dressings and amplified in a
      specific nested PCR assay. C. diffluens and C. liquefaciens DNA were detected in
      dressings from 97% (35/36) and 86% (31/36) of the AD patients and 47% (14/30) and
      37% (11/30) of the healthy subjects, respectively. These findings show that
      Malassezia spp. are not the only yeasts that colonize the skin of AD patients;
      Cryptococcus spp. also are present in a high proportion of patients. The role of
      these microorganisms in AD is as yet unknown, but the current findings, in
      combination with previous results, indicate that C. diffluens, C. liquefaciens,
      M. globosa, and M. restricta together colonize the skin surface of AD patients at
      a high frequency.

PMID- 14695445
TI  - Effects of high amylose maize starch and Clostridium butyricum on metabolism in
      colonic microbiota and formation of azoxymethane-induced aberrant crypt foci in
      the rat colon.
AB  - High amylose maize starch (HAS) is not digested in the small intestine and most
      of it reaches the large intestine. In the large intestine, HAS is fermented by
      intestinal bacteria, resulting in production of short-chain fatty acids (SCFA),
      particularly butyrate. Clostridium butyricum can utilize HAS and produce butyrate
      and acetate. It has been proposed that butyrate inhibits carcinogenesis in the
      colon. In this study, we examined the inhibitory effects of HAS and C. butyricum
      strain MIYAIRI588 (CBM588) on azoxymethane-induced aberrant crypt foci (ACF)
      formation in rats. In the group of rats administered only CBM588 spores, the
      concentration of butyrate in the cecum increased, but there was no decrease in
      the number of ACF. In the group of rats fed an HAS diet, a decrease in the number
      of ACF was observed, and in the group of rats administered HAS and CBM588, the
      number of ACF decreased significantly. In these two groups, the concentrations of
      acetate and propionate in intestinal contents significantly increased, but the
      concentration of butyrate did not change. It was found that the beta
      glucuronidase activity level of colonic contents decreased significantly in the
      two groups of rats fed HAS. This study showed that HAS and CBM588 changed the
      metabolism of colonic microbiota and decreased the level of beta-glucuronidase
      activity, phenomena that may play a role in the inhibition of ACF formation in
      the rat colon.

PMID- 14695446
TI  - Human cytomegalovirus (HCMV) IE1 plays role in resistance to apoptosis with
      etoposide in cancer cell line by Cdk2 accumulation.
AB  - Human cytomegalovirus (HCMV) has many strategies to survive the attack of the
      host. HCMV infection of host cells induces cellular activation and disturbance of
      the cell cycle. It is possible that HCMV modulates the behavior of certain cancer
      cells that are susceptible to HCMV infection. This study was performed to
      identify the possible mechanism of resistance to apoptotic stimuli in some cancer
      cell lines by HCMV infection. HCMV-infected cancer cells showed resistance to
      apoptosis induced by the topoisomerase II inhibitor etoposide. UMG1-2, which
      constitutively expresses HCMV immediate-early protein-1 (IE1), had resistance to
      apoptosis induced by etoposide as compared with the parental cell line U373MG.
      Measurement of caspases activity with fluorogenic substrates in etoposide-treated
      U373MG and UMG1-2 cells and the direct activation of caspase-3 with peptides
      containing arginine-glycine-aspartate in U373MG and UMG1-2 cells revealed that
      the inhibition level of apoptosis by HCMV IE1 would be upstream of caspase-3 in
      the caspase cascade pathway. Cellular expression of Cdk2 was increased in UMG1- 2
      after etoposide treatment while the expression of E2F-1 in UMG1-2 was decreased
      as compared with that in U373MG. The Cdk2 inhibitor, roscovitine, decreased the
      resistance to apoptosis on etoposide-treated UMG1-2. These results suggest that
      aberrant HCMV infection confers resistance to anticancer drugs on some cancer
      cells and protects cells from apoptosis, possibly due to the deregulation of
      cyclin-dependent kinase by HCMV immediate-early protein.

PMID- 14695447
TI  - Genotype and subtype analyses of hepatitis B virus (HBV) and possible co
      infection of HBV and hepatitis C virus (HCV) or hepatitis D virus (HDV) in blood
      donors, patients with chronic liver disease and patients on hemodialysis in
      Surabaya, Indonesia.
AB  - Four subtypes (adw, adr, ayw, and ayr ) and eight genotypes (A to H) of the
      hepatitis B virus (HBV) have been identified. They appear to be associated with
      particular geographic distribution, ethnicity, and possibly clinical outcomes. In
      this study, hepatitis B surface antigen (HBsAg) subtyping and HBV genotyping were
      carried out on sera obtained from HBsAg-positive HBV carriers, including healthy
      blood donors; patients with acute hepatitis, chronic hepatitis, liver cirrhosis,
      and hepatocellular carcinoma; and patients on hemodialysis all located in
      Surabaya, Indonesia. We report here that all HBV isolates tested in Surabaya
      belonged to genotype B, with more than 90% of them being classified into subtype
      adw. Our results also revealed that prevalence of hepatitis C virus (HCV) co
      infection among HBV carriers in Surabaya was approximately 10% for healthy blood
      donors and patients with chronic liver disease, and approximately 60% for
      patients on maintenance hemodialysis. Interestingly, HBsAg titers were lower in
      HBV carriers with HCV co-infection than in those without HCV co-infection. We
      also found that prevalence of hepatitis D virus (HDV) co-infection was < 0.5%
      among HBV carriers in Surabaya.

PMID- 14695448
TI  - Characterization of a slow-migrating component of the rabies virus matrix protein
      strongly associated with the viral glycoprotein.
AB  - We investigated multiple forms of rabies virus matrix (M) protein. Under non
      reducing electrophoretic conditions, we detected, in addition to major bands of
      monomer forms (23- and 24-kDa) of M protein, an M antigen-positive slow-migrating
      minor band (about 54 kDa) in both the virion and infected cells. Relative
      contents of the 54-kDa and monomer components in the virion were about 20-30% and
      70-80% of the whole M protein, respectively, while the content of the 54-kDa
      component was smaller (about 10-20% of the total M protein) in the cell than in
      the virion. The 54-kDa components could be extracted from the infected cells with
      sodium deoxycholate, but they were quite resistant to extraction with 1% nonionic
      detergents by which most monomer components were solubilized. The 54-kDa
      component was precipitated more efficiently than the monomer by a monoclonal
      antibody (mAb; #3-9-16), which recognized a linear epitope located at the N
      terminal of the M protein. The mAb #3-9-16 coprecipitated the viral glycoprotein
      (G), which was demonstrated to be due to strong association between the G and 54
      kDa component of the M protein. Monomers and the 54-kDa polypeptide migrated to
      the same isoelectric point (pI) in twodimensional (2-D) gel electrophoresis,
      implicating that the 54-kDa component was composed of component(s) of the same pI
      as that of the M protein monomers. From these results, we conclude that the M
      antigen-positive 54-kDa polypeptide is a homodimer of M protein, taking an N
      terminal-exposed conformation, and is strongly associated with the viral
      glycoprotein. Possible association with a membrane microdomain of the cell will
      be discussed.

PMID- 14695449
TI  - Morphological properties of a human intestinal spirochete first isolated from a
      patient with diarrhea in Japan.
AB  - A human intestinal spirochete isolated from a rectal biopsy specimen was
      morphologically characterized. The isolate was comma-shaped, 3-6 microm in
      length, 0.2 micro m in diameter and had tapered ends. The surface layer, external
      to the outer envelope, was amorphous. Four string-like periplasmic flagella with
      a diameter of 20 nm were presented at each end of the SDS-treated cells. Thin
      sections of the bacterial cell revealed a high-density cytoplasmic membrane and
      flagella in the periplasmic space between the cytoplasmic membrane and the outer
      envelope. Three segments of equal length were observed in some of the cells,
      while other cells were bi-segmented and more frequently observed.

PMID- 14695450
TI  - Induction of protective immunity by primed B-1 cells in Toxoplasma gondii 
      infected B cell-deficient mice.
AB  - We examined the role of B-1 cells in protection against Toxoplasma gondii
      infection using B cell-deficient mice (muMT mice). We found that primed but not
      naive B-1 cells from wild-type C57BL/6 mice protected B cell-deficient recipients
      from challenge infection. All muMT mice transferred with primed B-1 cells
      survived more than 5 months after T. gondii infection, whereas 100% of muMT mice
      transferred with naive B-1 cells succumbed by 18 days after infection.
      Additionally, high expression of both T help (Th) 1- and Th2-type cytokines and a
      high level of nitric oxide production were observed in T. gondii-infected muMT
      mice transferred with primed B-1 cells. Thus, it was clearly demonstrated that B
      1 cells play an important role in host protection against T. gondii infection in
      muMT mice.

PMID- 14695451
TI  - Bacterial artificial chromosome library of Finegoldia magna ATCC 29328 for
      genetic mapping and comparative genomics.
AB  - We constructed a bacterial artificial chromosome (BAC) library of Finegoldia
      magna ATCC 29328 DNA to facilitate further genome analysis of F. magna. The BAC
      library contained 385 clones with an average insert size of 55 kb, representing a
      10.1-fold genomic coverage. Repeated DNA hybridization using primer sets designed
      on the basis of BAC-end sequences yielded nine contigs covering 95% of the
      chromosome and two contigs covering 98% of the plasmid. The contigs were
      localized on the physical map of F. magna ATCC 29328 DNA. A total of 121 BAC-end
      sequences revealed 103 unique genes, which had not been previously reported for
      F. magna. The homolog ORF of albumin-binding protein (urPAB), one of the known
      virulence factors from F. magna, was sequenced and localized on the physical map.
      Homology analysis of 121 BAC-end sequences revealed that F. magna is most closely
      related to clostridia, particularly Clostridium tetani. This close relationship
      is consistent with the recent classification of peptostreptococci based on 16S
      rRNA sequence analysis. The BAC library constructed here will be useful for the
      whole genome sequencing project and other postgenomic applications.

PMID- 14695452
TI  - Quantities of interleukin-12p40 in mature CD8alpha negative dendritic cells
      correlate with strength of TCR signal and determine Th cell development.
AB  - Strength of T cell antigen receptor (TCR) signaling drives the development of Th1
      and Th2 subsets from naive T helper precursors. The quantity of interleukin-12
      (IL-12) from antigen presenting cells (APC) is also profoundly involved in Th
      development. TCR signal strength and IL-12 production from dendritic cells (DCs)
      are linked by CD40 ligand (CD40L) expression on activated T cells. CD40L on the
      activated T cells interacts with CD40 on DC, resulting in induction of IL-12 from
      DCs. However, the subsets of DC in spleen that produce the IL-12 have not been
      clearly identified. Purification of DC subsets itself may provide maturation
      signals to immature DCs. Thus, we used non-purified mouse spleen cells to analyze
      IL-12 producing cells, near to steady states, during the interaction of naive T
      cells either with or without agonist. Mature CD86highCD8alpha- DCs in spleen
      mainly produced IL-12p40 after stimulation of high dose agonist. The ratio of
      CD40L positive T cells and IL-12p40 secreting CD86high DCs correlated with the
      concentration of agonist and Th1 development. However, anti-IL-12 did not
      completely inhibit the Th1 development. Altogether, strength of TCR signaling
      directs Th cell development by regulating CD40L expression on T cells which
      determines production of IL-12p40 from CD86high CD8alpha- DC via CD40.

PMID- 14695453
TI  - [Functional analyses of lipocalin-type and hematopoietic prostaglandin D
      synthases].
AB  - Prostaglandin (PG) D synthase (PGDS) catalyzes the isomerization of PGH(2) to
      PGD(2), which acts as an endogenous somnogen and an allergic mediator. There are
      two distinct types of PGDS: one is lipocalin-type PGDS (L-PGDS) localized in the
      central nervous system, male genitals, and heart; and the other is hematopoietic
      PGDS (H-PGDS) in mast cells and Th2 lymphocytes. L-PGDS is the same as beta
      trace, a major protein in human cerebrospinal fluid, and is also secreted into
      the seminal plasma and plasma. The L-PGDS concentration in various body fluids is
      useful as a marker for various diseases such as renal failure and coronary
      atherosclerosis. H-PGDS is a cytosolic enzyme and is a member of the Sigma class
      of glutathione S-transferase. We determined the X-ray crystallographic structures
      of H-PGDS and L-PGDS. We also generated the gene-knockout (KO) mice and the human
      enzyme-overexpressing transgenic mice for each PGDS. L-PGDS-KO mice lacked PGE(2)
      induced tactile allodynia and rebound of non-rapid eye movement sleep after sleep
      deprivation. Human L-PGDS-overexpressing transgenic mice showed an increase in
      non-rapid eye movement sleep due to accumulation of PGD(2) in the brain after
      tail clipping. H-PGDS-KO mice showed an allergic reaction weaker than that of the
      wild-type mice.

PMID- 14695454
TI  - [Prostaglandin D2 in allergy: PGD2 has dual receptor systems].
AB  - Allergic inflammations feature an accumulation of T helper 2 (Th2) cells,
      eosinophils, and basophils into the inflamed sites and are often triggered by
      antigen-IgE mediated activation of mast cells that secret a variety of mediators.
      Therefore, the mast cell is known as a conductor cell in allergic inflammations.
      Prostaglandin (PG) D(2) is the major prostanoid secreted from the activated mast
      cell and has long been implicated in allergic diseases. The involvement of PGD(2)
      in allergic inflammation has been corroborated by several studies. Two PGD(2)
      receptors are known as the DP receptor and CRTH2. CRTH2 differs from DP in its
      signal pathways: CRTH2 is coupled with Gi-type G protein and DP is coupled with
      Gs-type G protein. It was reported that DP-deficient mice subjected to ovalbumin
      induced asthma model systems showed suppressed allergic reactions. Functions of
      CRTH2 in vivo have not been clear, but CRTH2 mediates PGD(2)-dependent cell
      migration and the activation of Th2 cells, eosinophils, and basophils. Therefore,
      the CRTH2 signal seems to promote allergic disease. The findings from these in
      vivo and vitro studies suggest that PGD(2) secreted from activated mast cells may
      be involved in the formation and/or maintenance of allergic inflammations through
      its dual receptor systems.

PMID- 14695455
TI  - [PGD(2)/L-PGDS system in hypertension and renal injury].
AB  - Prostaglandin D(2) (PGD(2)) and its metabolites bind to the intracellular PPARs
      to regulate vasoactive substances involved in vascular remodeling through
      regulation of mRNAs transcription as well as through receptor-mediated
      mechanisms. PGD(2) decreases inducible NO, PAI-1, endothelin, and VCAM expression
      through inhibition to NF kappa B, STAT, or AP-1 transcription factors, which are
      regulated by cytokines/immune system. Moreover, transfer of L-PGDS (PGD(2)
      synthase) into the intracellular space of EC or SMC increases intracellular
      PGD(2), thereby decreasing these substances. PGD(2) attenuates in vivo organ
      injury mediated by cytokines and the immune system. The pretreatment with PGD(2)
      attenuates the liver damage and hemodynamic collapse following LPS. Dahl salt
      sensitive rats, with decreased PGD(2) in the outer medulla of the kidney, are
      prone to hypertensive kidney injury. Serum L-PGDS level is increased in renal
      dysfunction through a decrease in glomerular filtration. L-PGDS in urine may be
      derived from a failure of tubular reabsorption or from in situ synthesis. Urinary
      L-PGDS excretion markedly increases in the early stage of kidney injury, and
      urinary L-PGDS is a useful predictor of the forthcoming renal injury. Indeed,
      urinary L-PGDS precedes clinically overt proteinuria or other parameters
      indicating renal dysfunction in hypertension, primary renal diseases, and
      diabetes in humans. PGD(2)/L-PGDS system is a Cinderella of vascular biology.

PMID- 14695456
TI  - Physiology and pharmacology of the prostaglandin J2 family.
AB  - The prostaglandin (PG) J(2) family including PGJ(2), Delta(12)-PGJ(2), and 15
      deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) are metabolites of PGD(2). They had been
      known as powerful inhibitors of cell proliferation and viral replication until
      15d-PGJ(2) was found to be a natural ligand for peroxisome proliferator-activated
      receptor gamma (PPAR gamma). Since then, several new pharmacological actions of
      the PGJ(2) family have been found, such as pro- and anti-apoptotic effects, cell
      differentiation-inducing effects, and inhibitory effects on inflammatory
      processes, whether they depend on PPAR gamma or not. We reported that the PGJ(2)
      family, particularly 15d-PGJ(2), inhibits cell proliferation by reducing the
      expression of G(1) cyclins and inducing the expression of cyclin-dependent kinase
      inhibitor p21 and moreover, induces cell differentiation in vascular smooth
      muscle cells. In vascular endothelial cells, we found that 15d-PGJ(2) inhibits
      apoptotic cell death at least in part by the induction of the inhibitor of
      apoptosis protein c-IAP1. More importantly, physiological levels of laminar fluid
      shear stress loaded on endothelial cells upregulate the expression of lipocalin
      type PGD(2) synthase, which converts PGH(2) to PGD(2), the precursor of the
      PGJ(2) family. Based on these results, we have hypothesized that the PGJ(2)
      family synthesized in vascular wall plays an important physiological role to
      protect vascular cells from atherogenic stimuli.

PMID- 14695457
TI  - Elevated concentration of soluble vascular endothelial cadherin is associated
      with coronary atherosclerosis.
AB  - BACKGROUND: Vascular endothelial (VE)-cadherin, a Ca(2+)-dependent cell adhesion
      molecule, is expressed in atherosclerotic lesions by endothelial cells and is
      associated with neovascularization, although the relationship between circulating
      VE-cadherin and coronary artery disease has not been studied. METHODS AND
      RESULTS: The plasma concentration of VE-cadherin was measured in peripheral blood
      (femoral artery) and the coronary sinus of 24 patients with acute myocardial
      infarction (AMI), 26 with stable angina pectoris (AP), 18 with old myocardial
      infarction (OMI), and 30 control subjects (Control) who had no coronary artery
      stenosis on angiography. For the patients with AMI, blood samples were obtained
      in the acute (day 1) and chronic (day 21) phases. The plasma concentration of VE
      cadherin was measured by enzyme-linked immunosorbent assay. The correlation
      between the plasma VE-cadherin concentration and the Gensini score was also
      determined as an index of the severity of coronary atherosclerosis. The plasma
      concentrations of VE-cadherin (ng/ml) in both the peripheral and coronary sinus
      blood were higher in patients with AMI, AP, and OMI than in the control subjects,
      and were similar in the 3 groups with coronary artery disease (femoral artery:
      AMI 5.1+/-2.5, AP 4.7+/-2.4, OMI 4.5+/-3.3, Control 2.6+/-2.3; coronary sinus:
      AMI 5.6+/-2.6, AP 5.0+/-2.3, OMI 5.0+/-2.9, Control 2.4+/-2.1, respectively).
      Plasma VE-cadherin concentrations were higher in the coronary sinus than
      peripheral blood samples in patients with AMI (p<0.01), AP (p<0.01), and OMI
      (p<0.05). The plasma VE-cadherin concentration was the same in the acute and
      chronic phases in patients with AMI. In the 3 groups of patients with coronary
      disease, both the peripheral plasma VE-cadherin concentration and the coronary
      sinus concentration correlated with the Gensini score (r=0.32, p<0.01 and r=0.42,
      p<0.001, respectively). Multiple regression analysis revealed that the plasma VE
      cadherin concentration predicted the Gensini score independently of sex, age,
      hypertension, diabetes mellitus, smoking, and the lipid profiles. CONCLUSION:
      Increased secretion of VE-cadherin from the epicardial arteries is associated
      with the degree of coronary atherosclerosis, indicating the presence of
      atherosclerosis rather than disease activity.

PMID- 14695458
TI  - Increased expression of monocyte CD11a and intracellular adhesion molecule-1 in
      patients with initial atherosclerotic coronary stenosis.
AB  - BACKGROUND: Cell adhesion molecules have been implicated in the adhesion of
      leukocytes to endothelial cells and therefore play a role in atherosclerosis,
      which is a frequent cause of morbidity and mortality in patients with coronary
      artery disease (CAD) or undergoing hemodialysis (HD). The levels of expression of
      leukocyte adhesion molecules were evaluated in patients with CAD or HD. METHODS
      AND RESULTS: The expression of leukocyte (ie, neutrophil, monocyte and
      lymphocyte) surface CD11a, CD18, intracellular adhesion molecule-1 (ICAM-1), very
      late antigen-4 alpha (VLA-4 alpha) and L-selectin was investigated by flow
      cytometry in 20 patients who were initially diagnosed with CAD (CAD group), 15
      patients with coronary re-stenosed vessels (RESTE group), 20 undergoing HD (HD
      group) and 20 without CAD (CONT group). Monocyte surface expression of both CD11a
      and ICAM-1 in the CAD group was significantly higher than in the CONT group.
      Interestingly, when 15 patients with RESTE were analyzed, they showed monocyte
      CD11a and ICAM-1 expression levels comparable to those in the CONT group. On the
      other hand, there were no significant differences in the expression of CD11a,
      CD18, L-selectin or VLA-4 alpha between the HD group and CONT group, but monocyte
      L-selectin was increased in the CAD group compared with the CONT group.
      CONCLUSIONS: Because CD11a and CD18 are expressed on the cell surface as a
      heterodimer and ICAM-1 is a ligand for CD11a/CD18, this increased expression of
      CD11a and ICAM-1 may affect the development of initial atherosclerotic coronary
      stenosis, but not re-stenosis.

PMID- 14695459
TI  - Serum phospholipid transfer protein mass as a possible protective factor for
      coronary heart diseases.
AB  - BACKGROUND: Phospholipid transfer protein (PLTP) can generate pre-beta high
      density lipoprotein (HDL), an efficient acceptor of peripheral cholesterol, by
      mediating a process called HDL conversion. The transfer of phospholipids to
      immature HDL is also essential in maintaining reverse cholesterol transport. The
      phospholipid transfer activity of PLTP has been associated with various patho
      physiological conditions; however, little information is available concerning the
      relationship between PLTP mass and disease. METHODS AND RESULTS: Using a sandwich
      enzyme-linked immunosorbent assay, PLTP concentration was measured and related to
      the risk of developing cardiovascular disease in a worksite-based cohort of
      Japanese men (n=2,567). Multiple linear regression analysis showed significant
      associations between PLTP and HDL cholesterol, triglycerides, low-density
      lipoprotein cholesterol, and body mass index (standardized beta=0.395, -0.191, 
      0.064, and -0.064, respectively; R(2)=0.31). During the follow-up period, there
      were 10 cases of coronary heart disease (CHD) and 7 of stroke. The multivariate
      adjusted relative risk of CHD was 0.46 (95% confidence interval, 0.20-1.07) for
      an increase of 1 standard deviation in the PLTP value (p=0.071). PLTP
      concentration was not related to the risk of stroke. CONCLUSIONS: The results of
      this prospective study indicate that the serum PLTP concentration would serve as
      a predictor of CHD, independent of HDL cholesterol, triglycerides and other
      established risk factors.

PMID- 14695460
TI  - Successful treatment of refractory vasospastic angina with corticosteroids:
      coronary arterial hyperactivity caused by local inflammation?
AB  - BACKGROUND: Although vasospastic angina usually responds well to treatment with
      calcium antagonists and/or nitrates, there have been anecdotal case reports of
      refractory vasospastic angina resistant to intensive treatment with high doses of
      calcium antagonists and nitrates. METHODS AND RESULTS: Four patients with
      vasospastic angina, which was refractory to intensive treatment with high doses
      of calcium antagonists and nitrates, were completely controlled after
      administration of corticosteroids. Although none of the 4 patients showed
      eosinophilia, all had bronchial asthma or chronic thyroiditis, and in 2 cases,
      the activity of vasospastic angina corresponded with that of bronchial asthma.
      CONCLUSIONS: These findings suggest that in these patients, coronary spasm may
      have been induced by arterial hyperreactivity because of local inflammation in
      the coronary arterial wall and that the corticosteroids suppressed the arterial
      hyperreactivity by alleviating the inflammation. Corticosteroids may be
      considered as a treatment choice for patients with refractory vasospastic angina,
      particularly when the patient has an allergic tendency, such as bronchial asthma.

PMID- 14695461
TI  - Cardioprotective effects of magnesium sulfate in patients undergoing primary
      coronary angioplasty for acute myocardial infarction.
AB  - BACKGROUND: Experimental evidence indicates that magnesium sulfate may have
      potential cardioprotective properties as an adjunct to coronary reperfusion. The
      present study was designed to examine the hypothesis that magnesium might have
      beneficial effects on left ventricular (LV) function and coronary microvascular
      function in patients with acute myocardial infarction (AMI). METHODS AND RESULTS:
      The study population of 180 consecutive patients with a first AMI (anterior or
      inferior) underwent successful primary coronary intervention. Patients were
      randomized to treatment with either intravenous magnesium (magnesium group, n=89)
      or normal saline (control group, n=91). Pre-discharge left ventriculograms were
      used to assess LV ejection fraction (LVEF), regional wall motion (RWM) within the
      infarct-zone and LV end-diastolic volume index. The Doppler guidewire was used to
      assess coronary flow velocity reserve (CFVR) as an index of coronary
      microvascular function. Magnesium group subjects showed significantly better LV
      systolic function (LVEF 63+/-9% vs 55+/-13%, p<0.001; RWM: -1.01+/-1.29 SD/chord
      vs -1.65+/-1.11 SD/chord, p=0.004), significantly smaller LV end-diastolic volume
      index (63+/-17 ml/m(2) vs 76+/-20 ml/m(2), p<0.001), and significantly higher
      CFVR (2.95+/-0.76 vs 2.50+/-0.99, p=0.023) than controls. CONCLUSION: Magnesium
      sulfate as an adjunct to primary coronary intervention shows favorable functional
      outcomes in patients with AMI.

PMID- 14695462
TI  - Effects of anticoagulation intensity on hemostatic markers in patients with non
      valvular atrial fibrillation.
AB  - BACKGROUND: Elevation of hemostatic markers may account for the increased risk of
      ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). The aim
      of this study was to determine the effects of anticoagulation intensity on
      hemostatic markers in patients with NVAF. METHODS AND RESULTS: In 509 patients
      with NVAF, comprising 263 patients treated with warfarin and 246 patients without
      warfarin, the hemostatic markers of prothrombin fragment F1.2 (F1.2), fibrin D
      dimer, platelet factor 4 (PF4), and beta-thromboglobulin were determined and
      compared with those in 111 patients with sinus rhythm. F1.2 was inversely related
      with anticoagulation intensity and D-dimer increased with age. All hemostatic
      markers, except F1.2, were greater in patients with NVAF than in patients with
      sinus rhythm. F1.2 and D-dimer were significantly lower in patients with
      international normalized ratio (INR) > or =1.5 than in NVAF patients without
      warfarin and were not different between NVAF patients with INR of 1.5-1.9 and
      with INR > or =2.0. CONCLUSIONS: Low intensity of anticoagulation (INR 1.5-1.9)
      suppresses the elevated concentration of F1.2 and D-dimer in patients with NVAF,
      and might be favorable in Japanese patients with NVAF in view of the balance
      between prevention of thromboembolism and the adverse effect by warfarin (ie,
      bleeding).

PMID- 14695463
TI  - Cost-effectiveness analysis of carvedilol for the treatment of chronic heart
      failure in Japan.
AB  - BACKGROUND: The cost-effectiveness of beta-blocker use in patients with chronic
      heart failure (CHF) has never been elucidated in a Japanese study. METHODS AND
      RESULTS: A Markov model for outpatients with CHF was constructed to simulate
      remaining life expectancy and expected medical costs for each patient. Each
      patient was assumed that they received either carvedilol in addition to
      conventional therapies (ie, digitalis, diuretics, and angiotensin-converting
      enzyme inhibitors) or conventional therapies alone. Analyses were conducted both
      for each patient's remaining lifetime and for a period of 5 years. Analyses were
      performed from the perspective of Japanese healthcare insurance. Analysis for
      treatment over the course of each patient's expected life span with carvedilol
      plus conventional therapies versus conventional therapies alone yielded expected
      medical costs of 3.5 million yen and 5.5 million yen respectively, and a life
      expectancy of 121 months and 88 months, respectively. The analysis of a 5-year
      period yielded 1.4 million yen and 2.8 million yen in expected medical costs and
      49 and 45 months life expectancy, respectively, for carvedilol versus
      conventional therapy. CONCLUSIONS: Carvedilol treatment for CHF patients is a
      highly cost-effective method of therapy in the Japanese medical environment.

PMID- 14695464
TI  - Past history of obesity (overweight by WHO criteria) is associated with an
      increased risk of nonfatal acute myocardial infarction: a case-control study in
      Japan.
AB  - BACKGROUND: Obesity is an important risk factor for the occurrence of coronary
      artery disease (CAD) in Western countries and furthermore, it often coexists with
      other CAD risk factors such as hypertension, dyslipidemia and diabetes mellitus.
      However, it is uncertain whether obesity is a CAD risk factor in Japan because
      Japanese are relatively thin on average. METHODS AND RESULTS: The CAD risk
      associated with obesity (body mass index > or =25.0) 10 years before as well as
      at the time of the survey was assessed in a case - control study of acute
      myocardial infarction (AMI), which compared 660 AMI patients aged 40-79 years and
      1,277 community controls, matched to each case by sex, year of birth, and
      residence. The prevalence of current obesity did not show any material difference
      between cases and controls, but compared with controls, past obesity was much
      more frequent in cases. Even after controlling for other CAD risk factors, past
      obesity was associated with a 2-fold increase in the risk of AMI. Past obesity
      was associated with an increased risk of AMI even without current obesity.
      CONCLUSION: Past obesity is a CAD risk, even after weight reduction.

PMID- 14695465
TI  - Insulin resistance and fasting hyperinsulinemia are risk factors for new
      cardiovascular events in patients with prior coronary artery disease and normal
      glucose tolerance.
AB  - BACKGROUND: Insulin resistance and hyperinsulinemia are important risk factors
      for coronary artery disease (CAD) and cardiovascular event (CVE). However, their
      independent relationship to new CVE in patients with normal glucose tolerance
      (NGT) and CAD is not known. METHODS AND RESULTS: Subjects of this 3-year
      observational study were 102 patients with CAD. Plasma glucose and insulin
      concentrations were determined at 2 time points (baseline and post oral glucose
      tolerance test [OGTT]. The fasting plasma glucose <110 mg/dl and post-OGTT <140
      mg/dl was diagnosed as NGT (World Health Organization criteria). Insulin
      resistance was evaluated by the homeostasis model assessment of insulin
      resistance (HOMA-IR). Of the 102 patients, 23 had onset of new CVE, including 19
      with new CAD. They had significantly higher fasting and post-OGTT insulin levels
      and HOMA-IR than those without new CVE (P<0.01, 0.031 and <0.01, respectively).
      Using the univariate Cox proportional hazards model, fasting and post-OGTT
      insulin values, HOMA-IR and high density lipoprotein (HDL) cholesterol differed
      significantly between the 2 groups. The multivariate Cox model showed that the
      effect of fasting plasma insulin and HOMA-IR remained significant and independent
      of HDL cholesterol. CONCLUSION: Fasting hyperinsulinemia and high insulin
      resistance increased the risk of new CVE in patients with NGT and CAD.

PMID- 14695466
TI  - Relation of myocardial blood volume to left ventricular function and future
      cardiac events in patients with idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: The hypothesis that myocardial blood volume is associated with left
      ventricular (LV) dysfunction and future cardiovascular events in patients with
      idiopathic dilated cardiomyopathy (IDC) was tested using intravenous myocardial
      contrast echocardiography (MCE). METHODS AND RESULTS: Thirty-five patients with
      IDC and 10 age-matched healthy control subjects were enrolled. Using MCE,
      background-subtracted and peak myocardial contrast intensity (calibrated PMCI)
      were calculated as measures of myocardial blood volume. LV ejection fraction
      (LVEF) was calculated using the modified Simpson method. Patients with IDC were
      stratified into 2 groups according to the median value of the calibrated PMCI
      [high value group (n=17): calibrated PMCI > or = -22.7 dB, low value group
      (n=18): calibrated PMCI < -22.7 dB]. The calibrated PMCI was markedly reduced in
      patients with IDC compared with the control subjects (p=0.0025) and closely
      related to LVEF (r=0.688, p<0.0001). In the multivariate model, calibrated PMCI
      was the independent variable that predicted cardiac events in patients with IDC.
      According to the Kaplan-Meier analysis, cardiac event-free rates were
      significantly lower in the low-value group than in the high-value group (p<0.01).
      CONCLUSIONS: Myocardial blood volume is closely related to LV dysfunction and
      future cardiac events in patients with IDC.

PMID- 14695467
TI  - Beta-blockers prevent cardiac events in Japanese patients with myocardial
      infarction.
AB  - BACKGROUND: Although the favorable effects of beta-blockers in the treatment of
      myocardial infarction (MI) have been repeatedly demonstrated in Western
      countries, administration of this drug has been limited in Japan. METHODS AND
      RESULTS: The study group of 1,896 patients with MI was retrospectively divided
      into 1,029 patients treated by beta-blockers and 867 not treated by beta
      blockers, and the incidences of cardiac events, consisting of recurrent MI, death
      because of worsening heart failure, and sudden death, and cardiovascular events,
      comprising cardiac events and stroke, were compared in both groups. There were 45
      cardiac events (4.4%, 30.1 patients/1,000 patients. year) among the beta-blocker
      group, which was significantly less than the 56 cardiac events (6.5%, 52.3
      patients/1,000 patients. year) among the no-beta-blocker group (p<0.05). The
      total mortality was 92 (8.9%, 61.6 patients/1,000 patients. year) and 124 (14.3%,
      115.8 patients/1,000 patients. year), respectively, and cardiac death occurred in
      42 (4.1%, 28.1 patients/1,000 patients. year) and 53 (6.1%, 49.5 patients/1,000
      patients. year), respectively, indicating that both these events occurred
      significantly less in the beta-blocker group (p<0.01 and p<0.05). CONCLUSIONS:
      Beta-blockers prevent cardiac events in Japanese patients with MI. However, a
      placebo-controlled, double-blind, multicenter, clinical trial conducted on a
      large scale in Japan would further contribute more precise information of the
      useful effects of beta-blockers.

PMID- 14695468
TI  - Sarpogrelate, a 5-HT2 receptor blocker, may have a preconditioning-like effect in
      patients with coronary artery disease.
AB  - BACKGROUND: Sarpogrelate, a serotonin receptor blocker, increases collaterals via
      a platelet anti-aggregation effect and/or vasodilatation. However, a recent
      report showed a preconditioning effect of sarpogrelate that enhances the
      translocation of PKC-epsilon of cardiomyocytes, followed by opening of the
      mitochondrial K(ATP) channel via inhibition of serotonin release from platelets
      during ischemia, protecting against cellular injury in rabbit hearts without
      collaterals. The present study used a percutaneous coronary intervention (PCI)
      model to define the protective effect of sarpogrelate against ischemic injury and
      its mechanism in human coronary artery disease. METHODS AND RESULTS: The study
      enrolled 20 patients with single vessel disease of 75% or 90% stenosis in the
      proximal left anterior descending (LAD) artery on coronary angiography (CAG).
      Patients were randomly divided into a control group (n=10) and a sarpogrelate
      group (n=10). The Delta STmax (maximum ST elevation) and Sigma ST (sum of ST
      elevation) on the 12-lead ECG recorded in the late stages (ie, 90 s and 120 s)
      after inflation were significantly smaller in the sarpogrelate group than in the
      controls. There was no significant difference in collaterals on the right and
      left CAG or between the 2 groups. CONCLUSIONS: Sarpogrelate improves ischemic
      injury during PCI and may be related to a preconditioning-like mechanism rather
      than to stimulating collateral development.

PMID- 14695469
TI  - Clinical study of the efficacy of a cooled-tip catheter ablation system for
      common atrial flutter.
AB  - BACKGROUND: Radiofrequency catheter ablation (RF-CA) of common atrial flutter
      (AFL) requires the creation of a transmural incision to create a bidirectional
      conduction block in the cavotricuspid isthmus (ITH). METHODS AND RESULTS: RF-CA
      of the ITH using a cooled-tip system was carried out in 40 patients. In the
      'conventional' mode (CONV) of the system, RF energy was applied for 2 min with
      the temperature set at 60 degrees C and power of up to 50 W, and in the failed
      cases the 'cooled-tip' mode (COOL) was utilized at 45 degrees C with up to 30 W
      (with a 15 ml/min saline flow rate). Of the 40 patients, 29 crossed over from the
      CONV to the COOL after a failed ablation of the AFL. As a result, in all 40
      patients a complete linear incision could be created with either the COOL or the
      CONV, resulting in the successful abolition of the AFL. Complete bi-directional
      block was successfully created in all patients. No significant side effects
      occurred. CONCLUSIONS: The COOL was found to be more effective and just as safe
      as the CONV for AFL ablation, thus facilitating the rapid and complete
      elimination of the AFL.

PMID- 14695470
TI  - Time course of electrocardiographic changes in patients with tako-tsubo syndrome:
      comparison with acute myocardial infarction with minimal enzymatic release.
AB  - BACKGROUND: The time course of the electrocardiographic (ECG) changes in patients
      with tako-tsubo syndrome remains unknown. METHODS AND RESULTS: In the present
      study, 16 patients with tako-tsubo syndrome and 15 patients with anterior acute
      myocardial infarction with minimal enzymatic release (minimal AMI) were
      evaluated. Left ventricular dysfunction dramatically resolved approximately 2
      weeks later in both groups. In the patients with tako-tsubo syndrome, the
      admission ECG usually showed ST segment elevation, especially in leads V(3-6). T
      wave inversion deepened progressively to its first negative peak, which occurred
      at approximately 3 days. The T wave was shallow for several days and then
      deepened again, the second negative peak occurring at approximately 2-3 weeks.
      The QT interval was prolonged as the T wave deepened, and shortened as the T wave
      became shallow. In the patients with minimal AMI, a similar time course of ECG
      changes was observed after reperfusion. In general, at 3 days or later during the
      early phase, T wave inversion was deeper and the QTc interval was longer in tako
      tsubo syndrome than in minimal AMI. CONCLUSIONS: Because the time course of the
      ECG changes, as well as that of the left ventricular dysfunction, is similar
      between tako-tsubo syndrome and minimal AMI, these 2 cardiac disorders must be
      carefully differentiated.

PMID- 14695471
TI  - Wolff-Parkinson-White (WPW) syndrome in isolated noncompaction of the ventricular
      myocardium (INVM).
AB  - Isolated noncompaction of the ventricular myocardium (INVM) is a rare
      morphological abnormality caused by cessation of the compaction of the loose
      interwoven meshwork of myocardial fibers during intrauterine life. Three cases of
      INVM, including 2 siblings, were diagnosed from 2-dimensional echocardiographic
      findings of Wolff-Parkinson-White syndrome type B to which INVM can be
      attributed.

PMID- 14695472
TI  - Multiple coronary artery fistulas with a huge right coronary artery showing
      exacerbation during 16 years of follow-up.
AB  - A 38-year-old Japanese woman underwent cardiac evaluation to assess an arrhythmia
      detected after the delivery of her fourth baby. At the age of 22 years, she had
      undergone cardiac evaluation, including catheter examination, because of a heart
      murmur. Coronary angiography showed a huge right coronary artery (RCA) draining
      to the right atrium and a normal left coronary artery. Because the left to right
      shunt ratio was trivial and the patient was asymptomatic, conservative
      observation was undertaken. On the current admission to hospital, there was a
      grade III continuous murmur at the second left sternal border. The patient
      underwent right and left cardiac catheter examination in March 2000. Selective
      coronary angiography demonstrated an enlarged lumen of the RCA, an enlarged
      aneurysmal cavity in the terminal portion of the RCA, and the postero-descending
      artery being filled by collateral circulation from the left coronary artery.
      Moreover, 2 new fistulas had appeared from the left coronary system. An oxygen
      saturation study showed that the pulmonary to somatic flow ratio (Qp/Qs) was 2.2.
      The patient underwent surgical treatment in July 2000 and on coronary angiography
      1 month later, there was no abnormal shunt flow from either coronary artery into
      the aneurysmal cavity, although the RCA was still enlarged.

PMID- 14695473
TI  - Stent-graft placement for mycotic aneurysm of the thoracic aorta: report of a
      case.
AB  - A 66-year-old man was found to have a mycotic aneurysm of the thoracic aorta. It
      was first suspected to be a pseudoaneurysm of the descending thoracic aorta on
      computed tomography scan, and the blood cultures were positive for methicillin
      resistant Staphylococcus aureus (MRSA). It was subsequently diagnosed as a
      mycotic aneurysm, but because the patient continued to do so poorly with
      septicemia, conventional surgery (ie, aortic exclusion and extraanatomic bypass,
      or surgical placement of in situ graft) was not performed. A stent-graft device
      composed of several units of self-expandable Z stents covered with ultra-thin
      woven Dacron was inserted through 21F sheath via the left external iliac artery
      and aortography showed successful deployment without blood endoleaks. The
      procedure was completed without incident and the patient has continued to do
      well. Endovascular stent-grafts may offer significant advantages for patients at
      high surgical risk.

PMID- 14695474
TI  - Congenital absence of the left circumflex coronary artery associated with acute
      myocardial infarction: a case report.
AB  - Among the congenital anomalies of the coronary arteries, a left circumflex artery
      (LCX) defect is extremely rare. A 49-year-old man who developed an acute anterior
      infarction underwent coronary angiography, which revealed complete occlusion of
      the left main trunk, but the territory usually supplied by the LCX had been
      perfused by the superdominant right coronary artery. Treatment of the left main
      trunk by percutaneous coronary intervention produced a favorable result. Accurate
      evaluation of the principal vessels and the extent of compensatory perfusion is
      important when diagnosing ischemic heart disease accompanied by anomalous
      coronary arteries and for choosing the best treatment modality.

PMID- 14695475
TI  - Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO.
AB  - The NF-kappaB family of transcription factors is activated in response to many
      stimuli, including pro-inflammatory cytokines, environmental stresses and, in the
      case of B and T lymphocytes, by antigenic stimulation. Bcl10 is essential for NF
      kappaB activation by T- and B-cell receptors. T and B lymphocytes from Bcl10
      deficient mice fail to activate NF-kappaB in response to antigen-receptor
      stimulation and, as a consequence, are unable to proliferate. Bcl10
      overexpression is sufficient to activate NF-kappaB, a process that requires the
      NF-kappaB essential modulator NEMO (also known as IKK-gamma), which is the
      regulatory subunit of the IkappaB kinase complex. However, the cellular mechanism
      by which Bcl10 activates the NF-kappaB pathway remains unclear. Here we show that
      Bcl10 targets NEMO for lysine-63-linked ubiquitination. Notably, a mutant form of
      NEMO that cannot be ubiquitinated inhibited Bcl10-induced NF-kappaB activation.
      Paracaspase and a ubiquitin-conjugating enzyme (UBC13) were both required for
      Bcl10-induced NEMO ubiquitination and subsequent NF-kappaB activation.
      Furthermore, short interfering RNAs that reduced the expression of paracaspase
      and UBC13 abrogated the effects of Bcl10. Thus, the adaptor protein Bcl10
      promotes activation of NF-kappaB transcription factors through paracaspase- and
      UBC13-dependent ubiquitination of NEMO.

PMID- 14695476
TI  - Regulation of neuromuscular transmission by neurotrophins.
AB  - Motor units comprise a motoneuron and the muscle fibers it innervates.
      Neuromuscular transmission is tightly regulated to match the activity of
      individual motor units. Activity-dependent release of neuromodulators at the
      neuromuscular junction (NMJ) determines the efficacy of transmission. The
      neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4)
      are produced by motoneurons and muscle fibers, and their release by skeletal
      muscle is regulated by muscle activity. BDNF and NT-4 enhance both spontaneous
      and evoked synaptic transmission at NMJs via activation of the tyrosine kinase
      receptor B (TrkB). Improvements in neuromuscular transmission may result from
      increased release of synaptic vesicles, either by presynaptic alterations in
      Ca(2+) transients or facilitated vesicular exocytosis. In fact, BDNF potentiates
      intracellular Ca(2+) release presynaptically and BDNF-induced TrkB activation
      also results in phosphorylation of synapsin I via mitogen activated protein
      kinase, which increases the number of synaptic vesicles available for release.
      Neurotrophins may also regulate synaptic transmission at the NMJ by increasing
      local release of neuregulin or other nerve-derived modulators. We review recent
      studies on the regulation of neuromuscular transmission, the motor unit-specific
      properties of NMJs and the effects of neurotrophins on synaptic efficacy at the
      NMJ.

PMID- 14695477
TI  - Calcitonin gene-related peptide gene therapy suppresses reactive oxygen species
      in the pancreas and prevents mice from autoimmune diabetes.
AB  - Reactive oxygen species (ROS) is involved in autoimmune destruction of islet beta
      cells, which has been proven to be an important underlying pathogenesis for
      insulin dependent diabetes mellitus (IDDM). Calcitonin gene-related peptide
      (CGRP) is a widely distributed neuropeptide, which has been found to play an
      important role in protecting myocytes from ROS. We hypothesized that exogenous
      CGRP gene administration before the pathogenic stage of insulitis might suppress
      the production of ROS and provide a hopeful therapeutic intervention for
      autoimmune diabetes. We performed CGRP gene transfer by injecting naked plasmid
      directly into skeletal muscles of mice with electroporation enhancement to
      achieve a continuous expression of CGRP in skeletal muscles, and thereby its
      secretion into the circulation. The effect of CGRP gene transfer on the
      pathogenesis of diabetes was studied in autoimmune diabetic mice induced by
      multiple low dose streptozotocin (MLDS). The CGRP gene therapy decreased
      morbidity of autoimmune diabetes, and significantly ameliorated hyperglycemia in
      these mice. CGRP gene transfer inhibited the production of ROS and
      malondialdehyde (MDA). In addition, it enhanced the activity of catalase (CAT)
      and superoxide dismutase (SOD) significantly. The data suggest that intramuscular
      CGRP gene transfer ameliorates autoimmune destruction of islet beta cells,
      resulting in significant reduction in diabetes incidence of MLDS diabetes mice.
      CGRP benefits might be mediated at least in part by inhibiting the oxidative
      stress in islet beta cells of these mice.

PMID- 14695478
TI  - Differential susceptibility of naive versus cloned CD4+ T cells to antigen
      specific and MHC-restricted anergy induction.
AB  - T cell anergy has been successfully induced under different conditions in cloned
      CD4(+) T cells, but induction of T cell anergy in vivo has been difficult and
      controversial. Due to the low frequency of naturally occurring T cell population
      with specificity to a defined antigen, it is very difficult to study anergy of
      naive T cells without prior in vivo priming which complicates the interpretation
      of experimental data. To solve this problem, we adopted the HNT-TCR transgenic
      mice which have homogeneous antigen specific CD4(+) T cell population. In this
      study, we generated an influenza virus hemagglutinin (HA) peptide-specific CD4(+)
      T cell clone from the HNT-TCR transgenic mice and induced anergy using APCs which
      were treated with the crosslinker, ECDI (1-ethyl-3-3(3-dimethylaminopropyl)
      carbodiimide). The proliferative response of the cloned or freshly purified naive
      CD4(+) transgenic T cells after treatment with ECDI-treated APCs and the HA
      peptide antigen was monitored as the index of anergy induction. The results
      showed that anergy was successfully induced in the cloned HNT-TCR transgenic
      CD4(+) T cells. It was determined that the induced anergy was antigen- and MHC
      specific. By contrast, anergy was not observed in freshly purified naive CD4(+)
      transgenic T cells under the same conditions. The results suggest that naive
      CD4(+) T cells may have different anergy inducing requirements, or that cloned
      CD4(+) T cells may have certain priming or in vitro cloning artifact which makes
      them more susceptible to anergy induction. We propose that induction of T cell
      anergy may depend on the T cell growth, activation and differentiation state or
      cloning conditions. The results from the present study may have important
      implications for the study of the mechanism(s) underlying T cell anergy induction
      in vivo and for applications of immune tolerance based therapy.

PMID- 14695479
TI  - Intramuscular injection of naked plasmid DNA encoding human preproinsulin gene in
      streptozotocin-diabetes mice results in a significant reduction of blood glucose
      level.
AB  - The insulin complement with gene therapy has been used as an experimental
      treatment for insulin dependent diabetes (IDDM). In the present study, we
      constructed naked plasmid DNA vector encoding recombinant human preproinsulin
      gene (pCMV-IN), and injected the plasmids (100 microg/mouse) intramuscularly
      combined with electroporation, to achieve the in vivo transfer of insulin gene in
      streptozotocin (STZ)-induced diabetic C57 mice. The expression of vector-derived
      insulin mRNA was detected with RT-PCR in transfected local skeletal muscles. The
      plasma insulin was elevated significantly in pCMV-IN injected diabetic C57 mice,
      which was complemented to the level similar to the intact normal control. The
      protein expression lasted for at least 35 days after the plasmid injection. Gene
      therapy with pCMV-IN plasmids considerably decreased the blood glucose level in
      STZ-induced diabetic mice from d 7 to d 35 by about 6 mmol/L. The gene therapy
      also reduced the mortality of severe diabetic mice significantly from 100% to 37%
      at the 6th week. Our results indicate that the direct intramuscular injection of
      naked plasmids encoding human preproinsulin gene achieves the effective
      expression of insulin. The restoration of insulin decreases blood glucose and
      increases the survival in severe diabetic mice. The gene therapy might be
      provided as a practical therapeutic approach to IDDM.

PMID- 14695481
TI  - Basolateral membrane mechanisms involved in ligustrazine-stimulated anion
      secretion in rat distal colon.
AB  - The present study investigated the cellular mechanism underlying the effect of
      ligustrazine on the ion transport in rat distal colon using the short-circuit
      current (I(SC)) technique. In freshly isolated colonic strips, basolateral
      addition of ligustrazine stimulated a rise in I(SC), which was resistant to
      basolateral application of neuronal sodium channel blocker tetrodotoxin (TTX),
      but inhibited by 55.2% by basolateral pretreatment with prostaglandin inhibitor
      indomethacin. The ligustrazine-induced I(SC) increase was inhibited by apical
      application of Cl(-) channel blockers diphenylamine-2,2'-dicarboxylic acid (DPC)
      and glibenclamide. Basolaterally administered bumetanide, an inhibitor of Na(+)
      K(+)-2 Cl(-) cotransporter, inhibited ligustrazine-evoked current increases by
      85.2% and basolateral exposure to Ba(2+), a non-specific potassium channels
      blocker, and blocked the current by more than 90%, indicating that basolateral
      Na(+)-K(+)-2 Cl(-) cotransporter and K(+) channels played an important role in
      the effect of ligustrazine. The results suggested that ligustrazine could
      stimulate rat distal colon (-) secretion that is mediated by basolateral Na(+)
      K(+)-2 Cl(-) cotransporter and K(+) channel.

PMID- 14695480
TI  - [Relationship between hippocampal long term potentiation induction and activity
      of 26S proteasome].
AB  - The present study examined the changes in 26S proteasome activity and the signal
      molecule mechanism regulating 26S proteasome activity in long term potentiation
      (LTP) in rat hippocampal slices. The results are as follows: 26S proteasome
      activity was 190+/-14.3 cpm/(100 microg.2 h) before tetanus, a significant
      increase in 26S proteasome activity (273+/-18.3 cpm/(100 microg.2 h) was found 10
      min after tetanus, when the slope of fEPSP was markedly increased. Interestingly,
      26S proteasome activity returned to baseline level (210+/-12.8 cpm/(100 microg.2
      h) 60 min after tetanus. Moreover, the N-methyl-D-aspartate (NMDA) receptor
      inhibitor AP-5, which blocked LTP, prevented the increase in the 26S proteasome
      activity. The results suggest that NMDA receptors contribute to the transient
      increase in 26S proteasome activity during induction of LTP in the hippocampal
      CA1 region.

PMID- 14695483
TI  - [Electrical activities of bursting-firing neurons in epileptic network
      reestablishment of rat hippocampus].
AB  - The purpose of our present work was to study the discharge of bursting-firing
      neurons (BFNs) in ipsilateral or contralateral hippocampus (HPC), and its
      relations to the reestablishment of local epileptic networks. The experiments
      were performed on 140 Sprague Dawley male rats (150-250 g). Acute tetanization
      (60 Hz, 2 s, 0.4 -0.6 mA) of the right posterior dorsal hippocampus (ATPDH) was
      administered to establish rat epilepsy model. The single unit discharges and the
      depth electrographs were simultaneously recorded from ipsilateral or
      contralateral HPC. In other experimental rats, acute tetanization of the right
      anterior dorsal HPC (ATADH) was used. Extracellular unit discharges in the CA1
      region were simultaneously recorded from bilateral anterior dorsal hippocampi.
      Analysis of hippocampal BFN firing patterns before or after administration of the
      tetanization was focused on according to their location in the HPC epileptic
      networks in vivo. Single unit discharges of 138 hippocampal neurons were recorded
      from ipsilateral and/or contralateral anterior dorsal HPC. Of the 138 neurons
      recorded, 19 were BFNs. 13 BFNs were tetanus-evoked and the remaining 6 were
      spontaneous ones. The evoked reactions of the single hippocampal neuron induced
      by the tetanization mainly included: (1) the firing patterns of the BFNs in
      ipsilateral anterior dorsal HPC were obviously modulated by the ATPDH from tonic
      firing into rhythmic bursting. The bursting interspike intervals (BISI)
      decreased. (2) There were mild modulations of the firing patterns of the BFNs in
      contralateral anterior dorsal HPC following post-inhibition of the firing rate of
      single neuron induced by the ATPDH. The interspike intervals (ISI) increased
      obviously. (3) Post-facilitation of rhythmic bursting-firing of the BFNs in
      contralateral anterior dorsal HPC was induced by ATADH; both the ISI and the IBI
      increased. (4) Synchronous or asynchronous rhythmic bursting-firing of the BFNs
      and the network epileptiform events ipsilateral or contralateral anterior dorsal
      HPC were elicited by the ATPDH. The results obtained suggest that bursting-firing
      of single BFNs is produced by the ATPDH in the anterior dorsal HPC along the
      longitudinal axis of the ipsilateral HPC or across the hemisphere to the opposite
      HPC. Rhythmic activities of the BFN may be implicated in the epileptic network
      reestablishment of the HPC. On the other hand, synaptic modulation of the BFN
      temporal series might be responsible for pathophysiological information
      transmission in the HPC-epileptic network.

PMID- 14695482
TI  - [Activating effect of ATP on NO/cGMP pathway in guinea pig cochlea].
AB  - The present investigation was to study the relationship between ATP and nitric
      oxide/cyclic guanosine monophosphate (NO/cGMP) pathway. Forty healthy purebred
      albino guinea pigs with sensitive pryer's reflex were randomly divided into five
      groups. Their cochleae were dissected and perfused immediately with different
      solutions. For the control group, the cochleae (group 1) were perfused with
      artificial perilymph basal solution (APBS, containing 100 micromol/L
      dipyridamole, 100 micromol/L L-Arg and 1 mmol/L IBMX). Other groups were
      respectively perfused group 2 with 330 micromol/L ATP, group 3 with 100
      micromol/L L-NNA+330 micromol/L ATP, group 4 with 10 micromol/L ODQ+330
      micromol/L ATP and group 5 with 10 micromol/L A-23187. All these reagents were
      freshly dissolved in artificial perilymph basal solution (APBS). The cochlear
      tissue specimens were collected and the average cGMP content was measured with
      (125)I-cGMP RIA kit. The results showed that there was no significant difference
      in the average cochlear tissue weights among different groups. The concentration
      of cGMP in the cochlear tissue of the groups perfused with ATP (59.541+/-8.744
      fmol/mg) and A-23187 (55.416+/-7.018 fmol/mg) was significantly higher than those
      of the control group (30.089+/-4.876 fmol/mg), the groups perfused with L-NNA+ATP
      (28.761+/-5.019 fmol/mg) and ODQ+ATP (34.209+/-13.658 fmol/mg). No significant
      difference was observed between the group perfused with ATP and the one with A
      23187, as well as among the control group and the groups perfused respectively
      with L-NNA+ATP and ODQ+ATP. These results suggest that ATP elevated the
      concentration of cGMP in cochlear tissue while administration of nonselective
      nitric oxide synthase inhibitor L-NNA and soluble guanylate cyclase inhibitor ODQ
      could prevent the increase of cGMP concentration induced by ATP. It is indicated
      that ATP is involved in the activation of NO/cGMP pathway by elevating
      concentration in the cytoplasm of the cochlea. In turn, NO/cGMP pathway may exert
      a negative action on the effects of ATP. It is suggested that there is an
      ATP/Ca(2+)-NO/cGMP pathway in the guinea pig cochlea. ATP and NO/cGMP pathway
      jointly regulate the function of the cochlea.

PMID- 14695484
TI  - [Changes in antioxidant capacity of the guinea pig exposed to noise and the
      protective effect of alpha-lipoic acid against acoustic trauma].
AB  - The study was aimed at exploring the effect of noise on total antioxidant
      capacity (TAC) in serum, nitric oxide (NO) level in the cochlea and the
      protective action of alpha-lipoic acid against noise-induced hearing loss (NIHL).
      Sixty guinea pigs (350-400 g) were divided randomly into three groups (control
      group, noise+saline group and noise+alpha-lipoic acid group). Serum and cochlear
      tissue were treated immediately after noise exposure (4-kHz octave band, 115 dB
      SPL 5 h) to determine the level of TAC and NO, respectively. Auditory brainstem
      responses (ABRs) were measured before and immediately after exposure. The
      threshold of hearing in the control group was relatively stable, while the
      hearing threshold in the noise+saline group was significantly higher than those
      in the noise+alpha-lipoic acid group (P<0.05). TAC level of the noise+saline
      group was significantly lower than that of the control group P<0.05 . TAC level
      of the noise+alpha-lipoic acid group was significantly higher than that of the
      noise+saline group P<0.05 , while there was no significant difference in the
      levels between the noise+alpha-lipoic acid group and the control group (P>0.05).
      The NO level of the cochlear tissue in the noise+saline group was significantly
      higher than that of the control group (P<0.05). Cochlear NO level in the
      noise+alpha-lipoic acid group was significantly lower than that of the
      noise+saline group (P<0.05), while there was no significant difference in
      cochlear NO levels between the noise+alpha-lipoic acid group and the control
      group (P>0.05). The results obtained indicate that noise exposure causes a
      decrease in serum TAC and an increase in NO in cochlea. alpha-Lipoid acid exerts
      a protective effect against hearing loss in acoustic trauma through its
      antioxidant effects.

PMID- 14695485
TI  - [Intrathecal injection of Sar9, Met(O2)11-substance P, neurokinin-1 receptor
      agonist, increases nitric oxide synthase expression and nitric oxide production
      in the rat spinal cord].
AB  - In the spinal cord, nitric oxide (NO) pathway is involved in pain and
      hyperalgesia, and nitric oxide synthase (NOS) expression and NO production are
      upregulated following several noxious and lesion stimuli. However, the mechanism
      of the increases is yet not well understood. The present study was designed to
      address the question of whether substance P (SP) released in the spinal cord
      enhances NOS expression and NO production of the spinal cord in rats. [Sar(9),
      Met(O2)(11)]-substance P (Sar-SP), a neurokinin-1 (NK-1) receptor agonist, was
      administered by intrathecal injection via L(5)-L(6) intervertebral space to
      induce nociception. The pain threshold was determined by hot water induced tail
      flick test. NOS expression of the L(5) segment of the spinal cord was determined
      using NADPH-d histochemical staining. NO production of the lumbar enlargement of
      the spinal cord was determined by assaying NO3(-) and NO2(-), the end product of
      NO metabolism, using the method of aqua fortis reduction. We found that (1)
      intrathecal injection of Sar-SP (6.5 nmol) elicited a characteristic, caudally
      directed, nociceptive behavioural response consisting of intense biting, licking
      and scratching episodes. Tail flick test showed decrease in pain threshold. (2)
      following the behavioural responses, the NOS expression level, including the
      number and the staining density of the NADPH-d reactive cells, increased in the
      superficial portion of the dorsal horn (Laminae I-II) and the grey matter
      surrounding the central canal (LaminaX) of the L(5) segment of the spinal cord
      after the Sar-SP intrathecal injection. At the same time, NO production in the
      enlargement of the spinal cord increased. (3) The decreased pain threshold and
      the increases in NOS expression and NO production could be substantially
      inhibited by intrathecal injection of [[D-Arg(1), D-Trp(7,9), Leu(11)]-substance
      P] (spantide) (5 microg), a non-selective antagonist of NK-1 receptor, 5 min
      prior to the Sar-SP injection. It might be concluded that the release of SP
      resulted from nociceptive afferents increased NOS expression and NO production of
      the rat spinal cord.

PMID- 14695486
TI  - [Role of inducible nitric oxide synthase in the vascular smooth muscle cells
      cycle arrest induced by 17 beta-estradiol].
AB  - Clinical epidemiologic data and animal experimental studies regard estrogen as
      being protective against the development of cardiovascular diseases. The
      mechanisms by which estrogen affects the development of vascular diseases are not
      clear. Recent studies demonstrated that the cardiovascular protective effects of
      estrogen are closely related to nitric oxide (NO) pathway. Our previous study
      proved that estrogen inhibited the proliferation and oncogene expression of
      vascular smooth muscle cells (VSMCs) induced by endothlin 1 (ET-1) and serum,this
      effect was mediated by NO release. In the present study, we investigated the role
      of inducible nitric oxide synthase (iNOS) in the VSMCs cycle arrest induced by 17
      beta-estradiol (E(2)). The effects of E(2) on iNOS activity and protein
      expression in cultured rat VSMCs and the influence of NOS inhibitor N(G)-nitro-L
      arginine methylester (L-NAME) on the inhibitory effect of E(2) on cell cycle were
      investigated. NOS assay kit was used to measure the activity of iNOS and protein
      expression of iNOS was determined by Western-blot. Cell cycle analysis was
      accessed by flow cytometry. The results obtained showed that E(2) increased iNOS
      activity of VSMCs but not in a dose-dependent manner. E(2) 10 nmol/L increased
      the iNOS activity of VSMCs distinctly at two time points: 30 min and 12 h. These
      effects were significantly inhibited by estrogen receptor (ER) antagonist
      Tamoxifen (0.1 micromol/L) and NOS inhibitor L-NAME (1 micromol/L). E(2)
      increased iNOS protein expression of VSMCs in a dose-dependent manner. The effect
      of E(2) on iNOS protein expression of VSMCs started at 3 h, distinctly increased
      at 12 h and then decreased. Tamoxifen significantly inhibited the E(2)-induced
      iNOS protein expression of VSMCs. ET-1 increased cell percentage of S phase and
      G(2)+S/G(1). This effect was inhibited by E(2). L-NAME significantly attenuated
      the inhibitory effect of E(2) on cell cycle of VSMCs. The results suggest that
      E(2) induced G(1) arrest of VSMCs, which was associated with an increase in iNOS
      activity and protein expression of VSMCs. These effects were at least mediated by
      estrogen receptor partly.

PMID- 14695487
TI  - [Binding between alpha 1A-adrenergic receptor and segment of bone morphogenetic
      protein-1 in human embryonic cell 293].
AB  - Using matchmaker yeast two-hybrid system, it has been demonstrated that there
      exists an interaction between the cellular C terminal of alpha(1A)-adrenergic
      receptor (alpha(1A)-AR) and a segment of bone morphogenetic protein-1 (BMP-1). In
      the present study binding between the two proteins was further determined in
      human embryonic cell 293 (HEK293), a mammalian expression system. Mammalian
      expression vector PCP3HA was constructed by PCR and consisted of segments of BMP
      1 cDNA, and vector PDT-alpha(1A) consisted of the full-length cDNA of human
      alpha(1A)-AR. They were transfected to HEK293 cells and examined by Western blot.
      alpha(1A)-AR and the segment of BMP-1 could be detected in the lysis of
      transfected cells. Then binding between alpha(1A)-AR and the segment of BMP-1 in
      HEK293 cell was determined by enzyme-linked immunosorbent assays (ELISA) and co
      immunoprecipitation. In ELISA experiment, the ELISA microwell plate was first
      coated with anti-FLAG M2 antibody, which recognizes the FLAG-tagged alpha(1A)-AR,
      then the cell lysis, anti-HA rabbit polyclonal antibody and HRP conjugated anti
      rabbit antibody were added in turn. The OD(490) values among the control group,
      PDT-alpha(1A) transfection group and PCP3HA transfection group, exhibited no
      significant difference (0.034+/-0.027, 0.042+/-0.019, 0.030+/-0.0096), but the
      OD(490) values of PDT-alpha(1A) and PCP3HA co-transfection group (0.57+/-0.12)
      were significantly higher than those of the other groups (P<0.001, respectively).
      In co-immunoprecipitation experiments, HEK293 cells expressing alpha(1A)-AR
      or/and segment of BMP-1 were lysed and incubated with anti-FLAG M2 antibody, then
      the immunoprecipitation pellet was immunoblotted with either the HRP conjugated
      anti-FLAG antibody or the anti-HA antibody, which recognizes the HA-tagged
      segment of BMP-1. Segment of BMP-1 was present in the pellet immunoprecipitation
      of PDT-alpha(1A) and PCP3HA co-transfected group. In conclusion, the results
      indicate that alpha(1A)-AR and the segment of BMP-1 are present in the same
      complex in HEK293 cells.

PMID- 14695488
TI  - [Roles of intracellular calcium and monomeric G-proteins in regulating exocytosis
      of human neutrophils].
AB  - Neutrophils play a major role in host defense against microbial infection. There
      are some clues indicate that neutrophils may also play a role in the
      pathophysiology of the airway obstruction in chronic asthma. We studied the roles
      of intracellular calcium and GTP gamma S in the regulation of neutrophils
      exocytosis using pipette perfusion and membrane capacitance measurement technique
      in whole cell patch clamp configuration. The results showed that the membrane
      capacitance increase induced by calcium revealed a biphasic process. The first
      phase occurred when the calcium level was between 0.2-14 micromol/L with a
      plateau amplitude of 1.23 pF and a calcium EC50 of 1.1 micromol/L. This phase
      might correspond to the release of the tertiary granules. The second phase
      occurred when the calcium concentration was between 20-70 micromol/L with a
      plateau increment of 6.36 pF, the calcium EC50 being about 33 micromol/L. This
      phase might represent the release of the primary and secondary granules.
      Intracellular calcium also simultaneously increased the exocytotic rate and the
      eventual extent in neutrophils. On the other hand, GTP gamma S can increase the
      exocytotic rate in a dose-dependent manner but had no effect on the eventual
      extent of membrane capacitance increment (>6 pF) if the cell was stimulated for a
      long period (>20 min). GTP gamma S (ranging from 20 to 100 micromol/L) induced
      the neutrophils to release all four types of the granules at very low
      intracellular calcium level.

PMID- 14695489
TI  - Morphological alteration of the hippocampal synapses in rats prenatally exposed
      to magnetic resonance imaging magnetic fields.
AB  - The present study investigated the effects of prenatal exposure to the magnetic
      resonance imaging (MRI) magnetic fields on the synaptic ultrastructure of
      hippocampal formation of rats at different postnatal development stages. Pregnant
      rats with gestation of 12-18 days were exposed to the magnetic fields used for
      MRI clinical applications. When the offspring were 1, 2, or 5-month-old, the
      synaptic morphologic parameters were measured in female offspring. In the 2-month
      old MRI group, the curvature of synaptic interface, the length of active zone and
      the surface density per unit volume (S(v)) of active zone in the dentate gyrus
      (DG) decreased significantly, and the width of synaptic cleft increased in the
      CA1 area. In the 5-month-old MRI group, the width of synaptic cleft increased,
      the thickness of postsynaptic density and the curvature of synaptic interface
      decreased significantly in the CA1 region, and the width of synaptic cleft
      increased in the DG. No significant change was observed in the 1-month-old group.
      These results suggest that prenatal exposure to the medical magnetic fields
      causes synaptic ultrastructural changes. The relationship of these changes with
      behavioral impairments was discussed.

PMID- 14695490
TI  - [Electrophysiological correspondence between Kv4.2 current and transient outward
      potassium current in the cultured rat hippocampal neuron].
AB  - The present study was carried out to determine the functional properties of Kv4.2
      expressed in mammalian cells in comparison with native transient potassium
      outward current (I(A)) in the hippocampal neurons. Transient transfection, cell
      culture and whole cell voltage clamp techniques were used. The results showed
      that I(A) in cultured rat hippocampal neurons and Kv4.2 expressed in HEK293 cells
      both displayed "A"-type current properties. The activation curves of I(A) and
      Kv4.2 were better fitted by simple Boltzmann function with V(1/2)   10.0+/-3.3
      mV, k 13.9+/-2.6 mV for I(A) and V1/2 -9.7+/-4.1 mV, k 15.8+/-5.7 mV for Kv4.2,
      respectively. The steady-state inactivation curves of I(A) had a midpoint of 
      93.0+/-11.4 mV and a slope of 9.0+/-1.5 mV. The voltage-dependence of
      inactivation for Kv4.2 exhibited midpoint and slope values of -59.4+/-12.2 mV and
      8.0+/-3.1 mV, respectively. The time constants (tau) of recovery from
      inactivation of I(A) and Kv4.2 were 27.9+/-14.1 ms and 172.8+/-10.0 ms,
      respectively. These results suggest that Kv4.2 is probably a major isoform
      contributing to I(A) in hippocampus neurons.

PMID- 14695491
TI  - [Effects of agmatine on neuronal discharges in rat hippocampal CA1 area].
AB  - The effects of agmatine (Agm) on the discharges of neurons in CA1 area of
      hippocampal slices were examined by using extracellular recording technique. The
      results are as follows. (1) In response to the application of Agm (0.1-1.0
      micromol/L) into the superfusate for 2 min, the spontaneous discharge rates (SDR)
      of 38/47 (80.9%) neurons were decreased significantly in a dose-dependent manner,
      while that of 9/47 (19.1%) neurons showed no change in discharge rate; (2)
      pretreatment with L-glutamate (L-Glu, 0.2 mmol/L) led to a marked increase in SDR
      of 9/12 (75%) neurons in an epileptiform pattern and that of 2/12 (25%) neurons
      were not affected, then after Agm (1.0 micromol/L) was applied into the
      superfusate for 2 min, the epileptiform discharges were suppressed significantly;
      (3) in 7 neurons, perfusion of the selective L-type calcium channel agonist, Bay
      K-8644 (0.1 micromol/L), induced an increase in the SDR of 6/7 (85.7%) neurons,
      while that of 1/7 (14.3%) neuron showed no change, and the discharges were also
      decreased by application of Agm (1.0 micromol/L) into the superfusate; and (4)
      application of NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 50
      micromol/L) into the superfusate 5 min later also significantly increased the SDR
      in all 13 (100%) neurons; then Agm (1.0 micromol/L) applied into the superfusate
      inhibited the discharges of 11/13 (84.6%) neurons, while those of 2/13 (15.4%)
      neurons were not affected. These results suggest that agmatine can inhibit the
      spontaneous discharges and L-glutamate-, Bay K-8644- and L-NAME-induced
      discharges of hippocampal CA1 neurons. These inhibitory effects of agmatine may
      be related to the blockade of NMDA receptors and a reduction in calcium influx in
      hippocampal neurons

PMID- 14695492
TI  - [Influence of pacing site on myocardial transmural dispersion of repolarization
      in intact normal and dilated cardiomyopathy dogs].
AB  - In order to verify the hypothesis that left ventricular epicardial (LV-Epi)
      pacing and biventricular (BiV) pacing unavoidably influence the myocardial
      electrophysiological characters and may result in high risk of malignant
      ventricular arrhythmia, we calculated, in both normal mongrel dogs and dog models
      with rapid-right-ventricular-pacing induced dilated cardiomyopathy congestive
      heart failure (DCM-CHF), the monophasic action potential duration (MAPD) and the
      transmural dispersion of repolarization (TDR) in intracardiac electrogram
      together with the QT interval and T(peak)-T(end) (T(p(-T(e)) interval in surface
      electrocardiogram (ECG) during LV-Epi and BiV pacing, compared with those during
      right ventricular endocardial (RV-Endo) pacing. To prepare the DCM-CHF dog model,
      rapid right ventricular pacing (250 bpm) was performed for 23.6+/-2.57 days to
      the dog. All the normal and DCM-CHF dogs were given radio frequency catheter
      ablation (RFCA) to His bundle with the guide of X-ray fluoroscopy. After the RFCA
      procedures, the animals were under the situation of complete atrioventricular
      block so that the canine heart rates could be voluntarily controlled in the
      following experiments. After a thoracotomy, ECG and monophasic action potentials
      (MAP) of subendocardial, subepicardial and mid-layer myocardium were recorded
      synchronously in 8 normal and 5 DCM-CHF dogs during pacing from endocardium of RV
      apex (RV-Endo), epicardium of LV anterior wall (LV-Epi) and simultaneously both
      of the above (biventricular, BiV), the later was similar to the ventricular
      resynchronization therapy to congestive heart failure patients in clinic. The Tp
      Te) meant the interval from the peak to the end of T wave, which was a
      representative index of TDR in surface ECG. The TDR was defined as the difference
      between the longest and the shortest MAPD of subendocardial, subepicardial and
      mid-layer myocardium. Our results showed that in normal dogs, pacing
      participating of LV (LV-Epi, BiV) prolonged MAPD of all the three layers of the
      myocardium (P<0.05) with the character that mid-layer MAPD was the longest and
      subepicardial MAPD was the shortest following subendocardial MAPD. At the same
      time, TDR prolonged from 26.75 ms at RV-Endo pacing to 37.54 ms at BiV pacing and
      to 47.16 ms at LV-Epi pacing (P<0.001). Meanwhile in surface ECG, BiV and LV-Epi
      pacing resulted in a longer Tp-Te) interval compared with RV-Endo pacing
      (P<0.01), without parallel QT interval prolongation. Furthermore, all the DCM-CHF
      model dogs showed manifestations of congestive heart failure and enlargement of
      left ventricles. Based on the lengthening of mid-layer MAPD from 257.35 ms to
      276.30 ms (P<0.0001) and increase of TDR from 27.58 ms to 33.80 ms (P
      equals;0.002) in DCM-CHF model due to the structural disorders of myocardium
      compared with the normal dog, LV-Epi and BiV pacing also led to the effect of
      prolonging MAPD of three layers of the myocardium and enlarging TDR. From these
      results we make the conclusions that prolongation of MAPD of subendocardial,
      subepicardial and mid-layer myocardium and increase in TDR during pacing
      participating of LV (LV-Epi, BiV) may contribute to the formation of
      unidirectional block and reentry, which play roles or at least are the high risk
      factors in the development of malignant ventricular arrhythmia, especially in
      case of structural disorders of myocardium. These findings must be considered
      seriously when ventricular resynchronization therapy is performed to congestive
      heart failure patients.

PMID- 14695493
TI  - Presynaptic alpha-7 nicotinic acetylcholine receptors modulate excitatory
      synaptic transmission in hippocampal neurons.
AB  - The effects of presynaptic nicotinic acetylcholine receptors (nAChRs) on
      excitatory synaptic transmission in CA1 pyramidal neurons of the rat hippocampus
      were examined by blind whole-cell patch clamp recording from hippocampal slice
      preparations. Local application of the nAChRs agonist dimethylphenyl-piperazinium
      iodide (DMPP) did not induce a postsynaptic current response in CA1 pyramidal
      cells. However, DMPP enhanced the frequency and amplitude of spontaneous
      excitatory postsynaptic current (sEPSC) in these cells in a dose-dependent
      manner. This enhancement was blocked by the selective nicotinic alpha-7 receptor
      antagonist alpha-bungarotoxin, but not by the antagonist mecamylamine,
      hexamethonium or dihydro-beta-erythroidine. The frequency of miniature excitatory
      postsynaptic current (mEPSC) in CA1 pyramidal neurons was also increased by
      application of DMPP, indicating a presynaptic site of action of the agonist.
      Taken together, these results suggest that activation of presynaptic nAChRs in
      CA1 pyramidal neurons, which contain alpha-7 subunits, potentiates presynaptic
      glutamate release and consequently modulate excitatory synaptic transmission in
      the hippocampus.

PMID- 14695494
TI  - [Effect of zinc on the corticosterone-induced injury of primary cultured rat
      hippocampal neurons].
AB  - The effect of zinc on the damage of primary cultured hippocampal neurons induced
      by corticosterone (CORT) was studied. Neuronal injury and expression of NMDA
      receptor subunits (NR1,NR2A,NR2B) mRNA were detected by using in situ staining
      and RT-PCR, respectively. Neurons treated with 5 micromol/L CORT for 24 h showed
      decreased survival rates and increased apoptotic rates compared with the
      controls; co-application of CORT and 10 or 100 micromol/L Zn(2+) attenuated
      apoptotic rates while 250 micromol/L Zn(2+) worsened CORT-induced neuronal
      injury. Expression of NR1, NR2B mRNA in neurons treated by 5 micromol/L CORT for
      24 h was significantly increased, while those concurrently added with 10 or 100
      micromol/L Zn(2+) showed no changes. No statistic difference in NR2A mRNA was
      obtained under any treatment. These results suggest that zinc can bilaterally
      regulate neuronal injuries induced by CORT, among while NMDA receptors probably
      play an important role.

PMID- 14695495
TI  - [An improved quantitative method for evaluating neurological deficits in mice
      with focal cerebral ischemia].
AB  - The purpose of this study was to develop a quantitative and objective method for
      evaluating neurological deficits in mice with focal cerebral ischemia. After
      middle cerebral artery occlusion (MCAO), the neurological deficits were evaluated
      24 h later. We measured the mean angles, dominant angles and turns in a hanged
      test in which the mice were sticked on the wall, and the holding angles in an
      inclined plane test as well, Then we determined the cerebral infarct volumes,
      neuron density in hippocampus, cortex and subcortical areas 24 h after MCAO. The
      correlations among infarct volume, neuron density and neurological deficits were
      analyzed. We also compared the quantitative method with two typical complex
      methods of behavioral assessment. The effect of [pranlukast, 4-oxo-8-[p-(4
      phenylbutyloxy) benzoylamino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate] (ONO
      1078), a neuroprotective agent, on ischemic injury was observed using this
      method. We found that the variables measured by both quantitative and typical
      behavioral methods significantly changed in the ischemic mice, and correlated
      with the infarct volumes and neuron densities. The quantitative variables well
      correlated with those of typical behavioral assessment, too. ONO-1078 inhibited
      ischemic injury and reduced the total scores of quantitative assessment. Thus,
      the quantitative method we developed is useful in evaluating neurological
      deficits of focal cerebral ischemia with the advantages of objectivity,
      quantification, simplicity and non-invasion, and can be used in the evaluation of
      neuroprotective effects of drugs.

PMID- 14695496
TI  - Tandem mass spectrometry in newborn screening.

PMID- 14695497
TI  - Working conditions and patient safety.

PMID- 14695498
TI  - A case study utilizing an enteral refeeding technique in a premature infant with
      short bowel syndrome.
AB  - Premature and full-term infants may be born with congenital abnormalities or
      develop acquired lesions of the gastrointestinal tract that require the placement
      of an enterostomy. Enterostomies can result in significant segments of excluded
      small bowel, creating a functional short bowel syndrome. Infants with
      enterostomies can develop dehydration, electrolyte imbalance, and failure to
      thrive. An illustrative case report of a premature infant with short bowel
      syndrome treated with enteral refeedings via a mucous fistula is presented. This
      report highlights the lessons learned from the interdisciplinary team's
      collective 10-year experience with enteral refeeding in infants with
      enterostomies. The physiologic basis for this approach is reviewed and literature
      reports are outlined. The specific nursing care and step-by-step techniques to
      deliver enteral refeeding through the mucous fistula are provided along with
      implications for clinical practice, education, and research.

PMID- 14695499
TI  - A case report of neonatal thyrotoxicosis due to maternal autoimmune
      hyperthyroidism.
AB  - A case of neonatal thyrotoxicosis secondary to maternal autoimmune
      hyperthyroidism is reported in an infant born at 34 weeks gestation who presented
      with tachycardia, jitteriness, diarrhea, and a small goiter. Propranolol and
      oxygen were used to treat high-output cardiac failure and transient persistent
      pulmonary hypertension. The infant's response to propylthiouracil therapy,
      gradual resolution of cardiac and systemic symptoms, and normaliziation of
      thyroid studies are described. Thyroid physiology and function and the special
      considerations in a premature infant are reviewed. An overview of maternal
      autoimmune hyperthyroidism and the implications for the developing fetus and
      neonate are presented. The risk factors for, and clinical presentation of,
      hyperthyroidism are outlined and treatment strategies highlighted. The nursing
      care of infants with hyperthyroidism is carefully described with an emphasis on
      the surveillance for and management of multisystem manifestations.

PMID- 14695500
TI  - Scalp hair characteristics in the newborn infant.
AB  - Scalp hair growth and patterning are closely associated with the development of
      the central nervous system. A number of genetic, metabolic, and neurologic
      disorders are associated with recognizable scalp hair abnormalities. For this
      reason, a systematic step-by-step assessment of the hair and scalp should be an
      integral part of every initial newborn physical assessment. This article reviews
      the clinically relevant embryology related to fetal scalp hair formation. Normal
      cycles of hair growth and loss are discussed. A systematic review of typical
      newborn scalp hair characteristics such as color, quantity, texture, direction of
      growth, hairlines, and hair whorls is provided. Conditions associated with
      abnormal hair color, quality, quantity, and distribution are presented in a
      series of clinical photographs, and their salient features are discussed.
      Abnormal hair often occurs as a constellation of findings; implications for
      clinical care and further investigation will be briefly described.

PMID- 14695501
TI  - A randomized controlled trial evaluating the efficacy of tetracaine gel for pain
      relief from peripherally inserted central catheters in infants.
AB  - BACKGROUND: Insertion of peripherally inserted central catheters (PICC) is a
      commonly performed procedure in both preterm and term infants. Tetracaine 4% gel
      (Ametop; Smith & Nephew Inc, St. Laurent, Quebec), a topical anesthetic, although
      reported to be effective for reducing the pain of venipuncture in neonates, has
      not been investigated for the management of pain associated with the PICC
      procedure. PURPOSE: To determine the efficacy of tetracaine gel for managing the
      pain associated with the PICC procedure in preterm and term infants. METHODS: A
      double-blind, placebo-controlled, randomized controlled trial (RCT) design was
      used. Infants undergoing nonurgent PICC insertion were randomized to receive
      either the treatment (1.0 g of tetracaine 4% gel) or placebo control (1.0 g of
      eucerin-plus cream) applied to the skin under occlusion for 30 minutes before the
      procedure. Data on the behavioral (facial expression) and physiologic (heart rate
      and oxygen saturation) indicators of pain were collected via videotaping and
      computer monitoring throughout the procedure. Data then were coded and measured
      by independent observers using the Premature Infant Pain Profile (PIPP; Stevens
      et al, 1996), and analyzed using descriptive statistics and repeated-measures
      analyses of variance. RESULTS: Forty-nine infants, gestational age 27 to 41 weeks
      (mean = 33; SD = 4.2) and age at time of insertion 2 to 85 days (mean = 18; SD =
      22.5) participated. No differences were found between the groups at the time of
      randomization. There were no adverse cardiorespiratory events or local skin
      reactions in either group. There was a significant within-subjects main effect of
      time across the procedure (F[48,3] = 11.03; P < 0.0001). There was no significant
      between-subjects main effect of group (F[48,1] = 0.11; P = 0.74) and no (group x
      time) interaction (F[48,3] = 0.45; P = 0.72). CONCLUSION: Tetracaine gel was not
      effective for pain relief for PICC insertion in infants. Its use for pain relief
      cannot be recommended based on the results of this study. Other pharmacologic,
      behavioral, and physical interventions should be investigated for safety and
      relief of procedural pain in this population of infants.

PMID- 14695502
TI  - Current concepts in universal newborn hearing screening and early hearing
      detection and intervention programs.
AB  - Newborns are routinely screened for hearing loss; screening typically occurs in
      the newborn nursery and newborn intensive care unit. Understanding the process
      and outcomes of initial hearing screening and ongoing early hearing detection and
      intervention programs (EHDI) are important roles of the newborn/neonatal
      intensive care (NICU) nurse. Infants that require NICU care are at higher risk of
      hearing loss and need close follow-up and repeat hearing testing throughout their
      first 3 years of life. Parents experience anxiety and worry related to potential
      hearing loss problems and need guidance, education, and information on infant
      hearing to ensure the best possible outcome for their infant.

PMID- 14695503
TI  - A parent's guide to newborn hearing screening.

PMID- 14695508
TI  - Structure-based enzyme engineering and its impact on in vitro glycorandomization.

PMID- 14695509
TI  - Synthesis of tissues and organs.
AB  - Symbolism that describes the synthetic processes for chemical compounds has been
      used to describe, in qualitative terms, the synthesis of tissues and organs at
      the correct anatomical site. The synthetic process is summarized in the reaction
      diagram, a shorthand representation of the reactants, reactor, and products.
      Analysis of a large number of independent protocols has led to identification of
      the simplest synthetic pathways for two organs that have been studied
      extensively: skin and peripheral nerves. These apparently irreducible reaction
      diagrams for the two organs are not only simple but surprisingly similar, a fact
      suggesting the existence of general rules for the synthesis of other organs as
      well. The only two reactants that are required are an active scaffold (a
      macromolecular network synthesized as a highly porous analogue of the
      extracellular matrix) and a seeding of epithelial cells of the organ being
      synthesized. Scaffolds possessed biological (regenerative) activity provided that
      they were capable of blocking the contraction process that leads to closure of
      the injured site. Such activity requires that the density of ligands for binding
      of contractile cells on the scaffold maintains a sufficiently high level over the
      period of synthesis.

PMID- 14695510
TI  - Chemical strategies for activity-based proteomics.
AB  - The assignment of molecular and cellular functions to the numerous protein
      products encoded by prokaryotic and eukaryotic genomes presents a major challenge
      for the field of proteomics. To address this problem, chemical approaches have
      been introduced that utilize small-molecule probes to profile dynamics in enzyme
      activity in complex proteomes. These strategies for activity-based protein
      profiling enable both the discovery and functional analysis of enzymes associated
      with human disease.

PMID- 14695511
TI  - Intraribosomal regulation of expression and fate of proteins.
AB  - Our studies of SecM (secretion monitor) in E. coli have revealed that some amino
      acid sequences can interact with ribosomal interior components, particularly with
      gate components of the exit tunnel, thereby interfering with their own
      translation elongation. Such translation arrest can be regulated by interaction
      of the N-terminal portion of the nascent polypeptide with other cellular
      components outside the ribosome. These properties of nascent proteins can in turn
      provide regulatory mechanisms by which the expression of genetic information at
      different levels is regulated.

PMID- 14695512
TI  - Gene therapy needs robust synthetic nonviral platform technologies.

PMID- 14695513
TI  - The activation of fibroblast growth factors (FGFs) by glycosaminoglycans:
      influence of the sulfation pattern on the biological activity of FGF-1.
AB  - Six synthetic heparin-like oligosaccharides have been used to investigate the
      effect of the oligosaccharide sulfation pattern on the stimulation of acidic
      fibroblast growth factor (FGF-1) induced mitogenesis signaling and the biological
      significance of FGF-1 trans dimerization in the FGF-1 activation process. It has
      been found that some molecules with a sulfation pattern that does not contain the
      internal trisaccharide motif, which has been proposed for high affinity for FGF
      1, stimulate FGF-1 more efficiently than those with the structure of the regular
      region of heparin. In contrast to regular region oligosaccharides, in which the
      sulfate groups are distributed on both sides of their helical three-dimensional
      structures, the molecules containing this particular sulfation pattern display
      the sulfate groups only on one side of the helix. These results and the fact that
      these oligosaccharides do not promote FGF-1 dimerization according to
      sedimentation-equilibrium analysis, confirm the importance of negative-charge
      distribution in the activation process and strongly suggest that FGF dimerization
      is not a general and absolute requirement for biological activity.

PMID- 14695514
TI  - Recognition of planar and nonplanar ligands in the malachite green-RNA aptamer
      complex.
AB  - Ribonucleic acids are an attractive drug target owing to their central role in
      many pathological processes. Notwithstanding this potential, RNA has only rarely
      been successfully targeted with novel drugs. The difficulty of targeting RNA is
      at least in part due to the unusual mode of binding found in most small-molecule
      RNA complexes: the ligand binding pocket of the RNA is largely unstructured in
      the absence of ligand and forms a defined structure only with the ligand acting
      as scaffold for folding. Moreover, electrostatic interactions between RNA and
      ligand can also induce significant changes in the ligand structure due to the
      polyanionic nature of the RNA. Aptamers are ideal model systems to study these
      kinds of interactions owing to their small size and the ease with which they can
      be evolved to recognize a large variety of different ligands. Here we present the
      solution structure of an RNA aptamer that binds triphenyl dyes in complex with
      malachite green and compare it with a previously determined crystal structure of
      a complex formed with tetramethylrosamine. The structures illustrate how the same
      RNA binding pocket can adapt to accommodate both planar and nonplanar ligands.
      Binding studies with single- and double-substitution mutant aptamers are used to
      correlate three-dimensional structure with complex stability. The two RNA-ligand
      complex structures allow a discussion of structural changes that have been
      observed in the ligand in the context of the overall complex structure. Base
      pairing and stacking interactions within the RNA fold the phosphate backbone into
      a structure that results in an asymmetric charge distribution within the binding
      pocket that forces the ligand to adapt through a redistribution of the positive
      partial charge.

PMID- 14695515
TI  - Proline-directed random-coil chemical shift values as a tool for the NMR
      assignment of the tau phosphorylation sites.
AB  - NMR spectroscopy of the full-length neuronal Tau protein has proved to be
      difficult due to the length of the protein and the unfavorable amino acid
      composition. We show that the random-coil chemical shift values and their
      dependence on the presence of a proline residue in the (i+1) position can
      successfully be exploited to assign all proline-directed phosphorylation sites.
      This is a first step toward the study of the phosphorylation of Tau by NMR
      spectroscopy.

PMID- 14695516
TI  - A (4R)- or a (4S)-fluoroproline residue in position Xaa of the (Xaa-Yaa-Gly)
      collagen repeat severely affects triple-helix formation.
AB  - The triple-helical fold of collagen requires the presence of a glycine residue at
      every third position in the peptide sequence and is stabilized by proline and
      (4R)-4-hydroxyproline residues in positions Xaa and Yaa of the (Xaa-Yaa-Gly)
      triplets, respectively. Regular down/up puckering of these Xaa/Yaa residues is
      possibly responsible for the tight packing of the three peptide strands, which
      have a polyproline-II-like structure, into the supercoiled helix. (4R)-Configured
      electronegative substituents such as a hydroxy group or a fluorine substituent on
      the pyrrolidine ring of the residue in the Yaa position favor the up pucker and
      thus significantly stabilize the triple helix. A similar effect was expected from
      the corresponding (4S)-isomers in the Xaa positions, but the opposite effect has
      been observed with (4S)-hydroxyproline, a result that has been speculatively
      attributed to steric effects. In this study, (4R)- and (4S)-fluoroproline
      residues were introduced into the Xaa position and potential steric effects were
      thus avoided. Contrary to expectations, (4S)-fluoroproline prevents triple-helix
      formation, whereas (4R)-fluoroproline stabilizes the polyPro II conformation, but
      without supercoiling of the three strands. The latter observation suggests that
      folding of the single chains into a polyproline II helix is not directly
      associated with triple helix formation and that fine tuning of van der Waals
      contacts, electrostatic interactions, and stereoelectronic effects is required
      for optimal packing into a triple helix.

PMID- 14695517
TI  - Fungal aerobic reductive dechlorination of ethyl 2-chloroacetoacetate by
      Saccharomyces cerevisiae: mechanism of a novel type of microbial dehalogenation.
AB  - Saccharomyces cerevisiae reduces the beta-keto ester ethyl 2-chloroacetoacetate
      to the respective chiral cis- and trans-beta-hydroxy esters. In the course of
      chiral reduction, competing dehalogenation of the xenobiotic substrate to ethyl
      acetoacetate occurs, in a reaction mediated by cytosolic glutathione (GSH).
      Mechanistically, the dechlorination is a novel type of glutathione-dependent
      dehalogenation catalysed by an as yet unidentified glutathione-dependent
      dehalogenase. The first step consists of a nucleophilic replacement of the
      chloride substituent by glutathione. In the subsequent enzyme-catalysed step, a
      second glutathione molecule liberates the dehalogenation product by thiolytic
      attack at the thioether bridge, resulting in a net transfer of two electrons to
      the substrate and in the formation of glutathione disulfide (GSSG). Being
      effective under aerobic conditions and catalysed by a fungus, this reductive
      dechlorination of an aliphatic substrate is an outstanding example of a novel,
      glutathione-mediated microbial dehalogenation.

PMID- 14695518
TI  - Unprecedented diversity of catalytic domains in the first four modules of the
      putative pederin polyketide synthase.
AB  - Polyketides of the pederin group are highly potent antitumor compounds found in
      terrestrial beetles and marine sponges. Pederin is used by beetles of the genera
      Paederus and Paederidus as a chemical defense. We have recently identified a
      group of putative pederin biosynthesis genes and localized them to the genome of
      an as yet unculturable Pseudomonas sp. symbiont, the likely true pederin
      producer. However, this polyketide synthase cluster lacks several genes expected
      for pederin production. Here we report an additional polyketide synthase encoded
      on a separate region of the symbiont genome. It contains at least three novel
      catalytic domains that are predicted to be involved in pederin chain initiation
      and the formation of an unusual exomethylene bond. The region is bordered by
      mobility pseudogenes; this suggests that gene transposition led to the disjointed
      cluster organization. With this work, all putative pederin genes have been
      identified. Their heterologous expression in a culturable bacterium will provide
      important insights into how sustainable sources of invertebrate-derived drug
      candidates can be created.

PMID- 14695520
TI  - Identification of luciferyl adenylate and luciferyl coenzyme a synthesized by
      firefly luciferase.
AB  - The firefly luciferase reaction intermediate luciferyl adenylate was detected by
      RP-HPLC analysis when the luciferase reaction was performed under a nitrogen
      atmosphere. Although this compound is always specified as an intermediate in the
      light-production reaction, this is the first report of its identification by HPLC
      in a luciferase assay medium. Under a low-oxygen atmosphere, luciferase can
      catalyze the synthesis of luciferyl coenzyme A from luciferin, ATP, and coenzyme
      A, but in air dehydroluciferyl coenzyme A was produced. The luciferase-catalyzed
      synthesis of these coenzyme A derivatives may be a consequence of the postulated
      recent evolutionary origin of firefly luciferases from an ancestral acyl-coenzyme
      A synthetase.

PMID- 14695519
TI  - Solution- and crystal-phase covalent modification of lysozyme by a purpose
      designed organoruthenium complex. A MALDI-TOF MS study of its metal binding
      sites.
AB  - Study of the reaction between the transition organometallic complex 4
      ruthenocenyl 2,6-dimethylpyrylium tetrafluoroborate and the enzyme hen egg white
      lysozyme (HEWL) in solution and by diffusion in crystals was performed by use of
      a combination of spectroscopic and chromatographic methods. Conjugation involving
      the lysine residues of lysozyme appeared to occur readily, yielding very stable
      ruthenocenyl pyridinium adducts with average degrees of incorporation ranging
      from 0.2 to 1.8 metal complexes per protein molecule, depending on reaction
      conditions. Matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) revealed that the protein conjugates were in fact
      mixtures of unmodified, mono-, di- and sometimes tripyridinium adducts. In
      combination with reversed-phased HPLC, we were able to show that six different
      monoruthenocenyl pyridinium adducts were formed in solution. This result was
      confirmed by trypsin digestion of a ruthenocenyl pyridinium conjugate and MALDI
      TOF MS analysis of the peptide mixture, which showed that lysines 1, 13, 33, 96,
      97 and 116 were involved in the reaction with the pyrylium complex, lysines 13,
      33 and 116 being the major binding sites. In the tetragonal crystal state, no
      binding of the ruthenium complex was shown to occur at lysine 116, owing to
      steric hindrance at this particular position.

PMID- 14695522
TI  - Template-directed assembly of metallosalen-DNA hairpin conjugates.

PMID- 14695521
TI  - Identification of a phosphopantetheinyl transferase for erythromycin biosynthesis
      in Saccharopolyspora erythraea.
AB  - Phosphopantetheinyl transferases (PPTases) catalyze the essential post
      translational activation of carrier proteins (CPs) from fatty acid synthases
      (FASs) (primary metabolism), polyketide synthases (PKSs), and non-ribosomal
      polypeptide synthetases (NRPSs) (secondary metabolism). Bacteria typically harbor
      one PPTase specific for CPs of primary metabolism ("ACPS-type" PPTases) and at
      least one capable of modifying carrier proteins involved in secondary metabolism
      ("Sfp-type" PPTases). In order to identify the PPTase(s) associated with
      erythromycin biosynthesis in Saccharopolyspora erythraea, we have used the genome
      sequence of this organism to identify, clone, and express (in Escherichia coli)
      three candidate PPTases: an ACPS-type PPTase (S. erythraea ACPS) and two Sfp-type
      PPTases (a discrete enzyme (SePptII) and another that is integrated into a
      modular PKS subunit (SePptI)). In vitro analysis of these recombinant PPTases,
      with an acyl carrier protein-thioesterase (ACP-TE) didomain from the erythromycin
      PKS as substrate, revealed that only SePptII is active in phosphopantetheinyl
      transfer with this substrate. SePptII was also shown to provide complete
      modification of ACP-TE and of an entire multienzyme subunit from the erythromycin
      PKS in E. coli. The efficiency of the SePptII in phosphopantetheinyl transfer in
      E. coli makes it an attractive alternative to other Sfp-type PPTases for co
      expression experiments with PKS proteins.

PMID- 14695523
TI  - An unprecedented catalytic motif revealed in the model structure of amide
      hydrolyzing antibody 312d6.

PMID- 14695524
TI  - Altering glucose oxidase to oxidize D-galactose through crosslinking of imprinted
      protein.

PMID- 14695526
TI  - VSD: a database for schizophrenia candidate genes focusing on variations.
AB  - Schizophrenia is a common mental disease characterized by delusions,
      hallucinations, and formal thought disorder. It has been demonstrated with
      genetic evidence that the disease is a polygenic disorder. Pharmacological,
      neurochemical, and clinical studies have suggested a number of schizophrenia
      susceptibility loci. In order to systematically search for genes with small
      effect in the development of schizophrenia, a database called VSD was established
      to provide variation data for publicly available candidate genes. Most of the
      genes encode neurotransmitter receptors, neurotransmitter transporters, and the
      enzymes involved in their metabolism. Other candidate genes extracted from
      published literature are also included. The variation information has been
      collected from publicly available mutation and polymorphism databases such as
      dbSNP, HGVbase, and OMIM, with single nucleotide polymorphism (SNP) being the
      most abundant form of collected variations. Reference sequences from NCBI's
      RefSeq database are used as references when positioning variation at transcript
      and protein levels. The nonsynonymous SNPs (nsSNPs) that lead to amino acid
      changes in the functional sites or domains of proteins are distinguished since
      they are more likely to affect protein function and would be target SNPs for
      association studies. In addition to variation data, gene descriptions, enzyme
      information, and other biological information for each gene locus are also
      included. The latest version of VSD contains 23,648 variations assigned to a
      total of 186 genes. Five-hundred eighty-eight domains and sites annotated in the
      SWISS-PROT and InterPro databases are found to contain nsSNPs. VSD may be
      accessed via the World Wide Web (www.chgb.org.cn/vsd.htm) and will be developed
      as an up-to-date and comprehensive locus-specific resource for identifying
      susceptibility genes for schizophrenia.

PMID- 14695527
TI  - Allelic genes of blood group antigens: a source of human mutations and cSNPs
      documented in the Blood Group Antigen Gene Mutation Database.
AB  - In this report, we analyze data assembled in the Blood Group Antigen Gene
      Mutation Database (www.bioc.aecom.yu.edu/bgmut/index.htm), which describes
      sequence information on human genes associated with expression of the various
      serologically-determined blood group phenotypes. The database documents 38
      genetic loci and a total of 624 alleles that together encode a large repertoire
      of proteins and constitute 27 serologically-defined blood group systems. Analysis
      of sequence variation patterns across alleles of a number of genes is focused on
      their molecular profiles, including mutational sites and recurrence, patterns of
      gene rearrangements in duplicated gene families, correlation of predicted
      location of epitopes in extracellular loops with sites of alterations, and
      effects of mutations on protein expression. That information, and the relative
      ease of identifying individuals bearing variant alleles, has led to the proposal
      that genes encoding blood group antigens are an important and unique resource for
      studies of human DNA variation. Another focus is on mutations in regions that
      encode the antigenic epitopes and on their occurrence in world populations. These
      mutations may be viewed as coding single nucleotide polymorphisms (cSNPs). We
      propose that one group of these cSNPs, which are known to occur with significant
      frequency in all world populations, could serve as well-validated genetic
      markers. In addition, specific mutations in a number of "low incidence" and rare
      alleles could serve as cSNPs specific for a given population. The allelic
      frequencies of these mutations and knowledge of their world-wide occurrence add a
      valuable dataset to the existing cSNP pools documented in SNP databases.

PMID- 14695528
TI  - Subtelomeric deletions detected in patients with idiopathic mental retardation
      using multiplex ligation-dependent probe amplification (MLPA).
AB  - Subtelomeric rearrangements are responsible for 5% to 10% of cases of unexplained
      mental retardation. Despite their clinical relevance, methods to screen for these
      cytogenetically invisible abnormalities on a routine base are scarce. We screened
      patients with idiopathic mental retardation for subtelomeric aberrations using
      multiplex ligation-dependent probe amplification (MLPA). This recently developed
      technique is based on PCR amplification of ligated probes hybridized to
      chromosome ends. Currently, 41 telomeres can be screened in just two multiplex
      reactions. Four subtelomeric rearrangements (5.3%) were detected in a group of 75
      patients with mild to severe mental retardation in combination with dysmorphic
      features and/or a familial history of mental retardation: two terminal 1p
      deletions, a terminal 1q deletion, and a terminal 3p deletion. Deletions could be
      verified by FISH and marker analysis. In one case the MLPA indicated a terminal
      21q deletion due to a 3-bp deletion at the site of the probe, giving a false
      positive rate of 1.3%. This study demonstrates that MLPA is a fast and reliable
      screening method, potentially suitable for use in routine diagnostics.

PMID- 14695529
TI  - Interaction between trypsinogen isoforms in genetically determined pancreatitis:
      mutation E79K in cationic trypsin (PRSS1) causes increased transactivation of
      anionic trypsinogen (PRSS2).
AB  - The human pancreas secretes two major trypsinogen isoforms, cationic and anionic
      trypsinogen. To date, 19 genetic variants have been identified in the cationic
      trypsinogen gene (PRSS1) of patients with hereditary, familial, or sporadic
      chronic pancreatitis. A common feature of cationic trypsinogen mutants studied so
      far is an increased propensity for autocatalytic activation (autoactivation).
      This is thought to lead to premature intrapancreatic digestive protease
      activation. In contrast, no pancreatitis-associated mutations have been found in
      the anionic trypsinogen gene (PRSS2), suggesting that this isoform might play a
      relatively unimportant role in pancreatitis. To challenge this notion, here we
      describe the unique properties of the E79K cationic trypsinogen mutation
      (c.235G>A), which was identified in three European families affected by sporadic
      or familial pancreatitis cases. In vitro analysis of recombinant wild-type and
      mutant enzymes revealed that catalytic activity of E79K trypsin was normal, and
      its inhibition by pancreatic secretory trypsin inhibitor was unaffected. Although
      the E79K mutation introduces a potential new tryptic cleavage site, autocatalytic
      degradation (autolysis) of E79K-trypsin was also unchanged. Furthermore, in
      contrast to previously characterized disease-causing mutations, E79K markedly
      inhibited autoactivation of cationic trypsinogen. Remarkably, however, E79K
      trypsin activated anionic trypsinogen two-fold better than wild-type cationic
      trypsin did, while the common pancreatitis-associated mutants R122H or N29I had
      no such effect. The observations not only suggest a novel mechanism of action for
      pancreatitis-associated trypsinogen mutations, but also highlight the importance
      of interactions between the two major trypsinogen isoforms in the development of
      genetically determined chronic pancreatitis.

PMID- 14695530
TI  - Five novel mutations in the lysosomal sialidase gene (NEU1) in type II sialidosis
      patients and assessment of their impact on enzyme activity and intracellular
      targeting using adenovirus-mediated expression.
AB  - Sialidosis is an autosomal recessive disease resulting from a deficiency of
      lysosomal sialidase. Type II sialidosis is a rare disease characterized
      clinically by hydrops fetalis, hepatosplenomegaly, and severe psychomotor
      retardation. Genomic DNA from four unrelated sialidosis patients was screened for
      mutations within the sialidase gene NEU1. Five novel mutations were identified.
      Four are missense and one is nonsense: c.674G>C (p.R225P), c.893C>T (p.A298V),
      c.3G>A (p.M1?), c.941C>G (p.R341G), and c.69G>A (p.W23X). We have used our
      findings and diagnostic tools to confirm the presence of a homozygous null allele
      in a neonate sibling. Recombinant adenoviruses expressing the mutant sialidase
      alleles in primary cell cultures were utilized to assess the impact of each
      mutation on enzyme activity and intracellular localization. None of the mutant
      alleles expressed significant enzymatic activity. The p.R341G mutation exerts its
      pathological effect by perturbing substrate binding, while the p.A298V and
      p.R225P mutations appear to impair the folding of the sialidase enzyme. Our
      findings point to mutation-sensitive amino acids involved in catalytic function
      or structural stability and indicate the potential utility of these mutations for
      molecular diagnosis of this rare disease.

PMID- 14695531
TI  - Solid renal tumor severity in von Hippel Lindau disease is related to germline
      deletion length and location.
AB  - von Hippel Lindau disease (VHL) is an autosomal dominant familial cancer syndrome
      linked to alteration of the VHL tumor suppressor gene. Affected patients are
      predisposed to develop pheochromocytomas and cystic and solid tumors of the
      kidney, CNS, pancreas, retina, and epididymis. However, organ involvement varies
      considerably among families and has been shown to correlate with the underlying
      germline alteration. Clinically, we observed a paradoxically lower prevalence of
      renal cell carcinoma (RCC) in patients with complete germline deletion of VHL. To
      determine if a relationship existed between the type of VHL deletion and disease,
      we retrospectively evaluated 123 patients from 55 families with large germline
      VHL deletions, including 42 intragenic partial deletions and 13 complete VHL
      deletions, by history and radiographic imaging. Each individual and family was
      scored for cystic or solid involvement of CNS, pancreas, and kidney, and for
      pheochromocytoma. Germline deletions were mapped using a combination of
      fluorescent in situ hybridization (FISH) and quantitative Southern and Southern
      blot analysis. An age-adjusted comparison demonstrated a higher prevalence of RCC
      in patients with partial germline VHL deletions relative to complete deletions
      (48.9 vs. 22.6%, p=0.007). This striking phenotypic dichotomy was not seen for
      cystic renal lesions or for CNS (p=0.22), pancreas (p=0.72), or pheochromocytoma
      (p=0.34). Deletion mapping revealed that development of RCC had an even greater
      correlation with retention of HSPC300 (C3orf10), located within the 30-kb region
      of chromosome 3p, immediately telomeric to VHL (52.3 vs. 18.9%, p <0.001),
      suggesting the presence of a neighboring gene or genes critical to the
      development and maintenance of RCC. Careful correlation of genotypic data with
      objective phenotypic measures will provide further insight into the mechanisms of
      tumor formation.

PMID- 14695532
TI  - Twenty-two novel mutations in the lysosomal alpha-glucosidase gene (GAA)
      underscore the genotype-phenotype correlation in glycogen storage disease type
      II.
AB  - Patients with glycogen storage disease type II (GSDII, Pompe disease) suffer from
      progressive muscle weakness due to acid alpha-glucosidase deficiency. The disease
      is inherited as an autosomal recessive trait with a spectrum of clinical
      phenotypes. We have investigated 29 cases of GSDII and thereby identified 55
      pathogenic mutations of the acid alpha-glucosidase gene (GAA) encoding acid
      maltase. There were 34 different mutations identified, 22 of which were novel.
      All of the missense mutations and two other mutations with an unpredictable
      effect on acid alpha-glucosidase synthesis and function were transiently
      expressed in COS cells. The effect of a novel splice-site mutation was
      investigated by real-time PCR analysis. The outcome of our analysis underscores
      the notion that the clinical phenotype of GSDII is largely dictated by the nature
      of the mutations in the GAA alleles. This genotype-phenotype correlation makes
      DNA analysis a valuable tool to help predict the clinical course of the disease.

PMID- 14695533
TI  - DGGE-based whole-gene mutation scanning of the dystrophin gene in Duchenne and
      Becker muscular dystrophy patients.
AB  - Duchenne and Becker muscular dystrophy (DMD and BMD) are caused by mutations in
      the dystrophin gene. Large rearrangements in the gene are found in about two
      thirds of DMD patients, with approximately 60% carrying deletions and 5-10%
      carrying duplications. Most of the remaining 30-35% of patients are expected to
      have small nucleotide substitutions, insertions, or deletions. To detect these
      subtle changes within the coding and splice site determining sequences of the
      dystrophin gene, we established a semiautomated denaturing gradient gel
      electrophoresis (DGGE) mutation scanning system. The DGGE scan covers the
      dystrophin gene with 95 amplicons, PCRed either individually or in a multiplex
      setup. PCR and pooling were performed semiautomatically, using a pipetting robot
      and 384-well plates, enabling concurrent amplification of DNA of four patients in
      one run. Amplification of individual fragments was performed using one PCR
      program. The products were pooled just before gel loading; DGGE requires only a
      single gel condition. Validation was performed using DNA samples harboring 39
      known DMD variants, all of which could be readily detected. DGGE mutation
      scanning was applied to analyze 135 DMD/BMD patients and potential DMD carriers
      without large deletions or duplications. In DNA from 25 out of 44 DMD patients
      (57%) and from 5 out of 39 BMD patients (13%), we identified clear pathogenic
      changes. All mutations were different, with the exception of one DMD mutation,
      which occurred twice. In DNA from 10 out of 44 potential DMD carriers, including
      four obligate carriers, we detected causative changes, including one pathogenic
      change in every obligate carrier. In addition to these pathogenic changes, we
      detected 15 unique unclassified variants, i.e., changes for which a pathogenic
      nature is uncertain.

PMID- 14695534
TI  - Nonclassical splicing mutations in the coding and noncoding regions of the ATM
      Gene: maximum entropy estimates of splice junction strengths.
AB  - Ataxia-telangiectasia (A-T) is an autosomal recessive neurological disorder
      caused by mutations in the ATM gene. Classical splicing mutations (type I) delete
      entire exons during pre-mRNA splicing. In this report, we describe nine examples
      of nonclassical splicing mutations in 12 A-T patients and compare cDNA changes to
      estimates of splice junction strengths based on maximum entropy modeling. These
      mutations fall into three categories: pseudoexon insertions (type II), single
      nucleotide changes within the exon (type III), and intronic changes that disrupt
      the conserved 3' splice sequence and lead to partial exon deletion (type IV).
      Four patients with a previously reported type II (pseudoexon) mutation all shared
      a common founder haplotype. Three patients with apparent missense or silent
      mutations actually had type III aberrant splicing and partial deletion of an
      exon. Five patients had type IV mutations that could have been misinterpreted as
      classical splicing mutations. Instead, their mutations disrupt a splice site and
      use another AG splice site located nearby within the exon; they lead to partial
      deletions at the beginning of exons. These nonclassical splicing mutations create
      frameshifts that result in premature termination codons. Without screening cDNA
      or using accurate models of splice site strength, the consequences of these
      genomic mutations cannot be reliably predicted. This may lead to further
      misinterpretation of genotype-phenotype correlations and may subsequently impact
      upon gene-based therapeutic approaches.

PMID- 14695535
TI  - Knobloch syndrome: novel mutations in COL18A1, evidence for genetic
      heterogeneity, and a functionally impaired polymorphism in endostatin.
AB  - Knobloch syndrome (KNO) is an autosomal recessive disorder characterized by high
      myopia, vitreoretinal degeneration with retinal detachment, and congenital
      encephalocele. Pathogenic mutations in the COL18A1 gene on 21q22.3 were recently
      identified in KNO families. Analysis of two unrelated KNO families from Hungary
      and New Zealand allowed us to confirm the involvement of COL18A1 in the
      pathogenesis of KNO and to demonstrate the existence of genetic heterogeneity.
      Two COL18A1 mutations were identified in the Hungarian family: a 1-bp insertion
      causing a frameshift and a premature in-frame stop codon and an amino acid
      substitution. This missense variant is located in a conserved amino acid of
      endostatin, a cleavage product of the carboxy-terminal domain of collagen alpha 1
      XVIII. D1437N (D104N in endostatin) likely represents a pathogenic mutation, as
      we show that the endostatin N104 mutant is impaired in its affinity towards
      laminin. Linkage to the COL18A1 locus was excluded in the New Zealand family,
      providing evidence for the existence of a second KNO locus. We named the second
      unmapped locus for Knobloch syndrome KNO2. Mutation analysis excluded COL15A1, a
      member of the multiplexin collagen subfamily similar to COL18A1, as being
      responsible for KNO2.

PMID- 14695536
TI  - A genetic polymorphism in the coding region of the gastric intrinsic factor gene
      (GIF) is associated with congenital intrinsic factor deficiency.
AB  - Congenital intrinsic factor (IF) deficiency is a disorder characterized by
      megaloblastic anemia due to the absence of gastric IF (GIF, GenBank NM_005142)
      and GIF antibodies, with probable autosomal recessive inheritance. Most of the
      reported patients are isolated cases without genetic studies of the parents or
      siblings. Complete exonic sequences were determined from the PCR products
      generated from genomic DNA of five affected individuals. All probands had the
      identical variant (g.68A>G) in the second position of the fifth codon in the
      coding sequence of the gene that introduces a restriction enzyme site for Msp I
      and predicts a change in the mature protein from glutamine(5) (CAG) to
      arginine(5) (CGG). Three subjects were homozygous for this base exchange and two
      subjects were heterozygous, one of which was apparently a compound heterozygote
      at positions 1 and 2 of the fifth codon ([g.67C>G] + [g.68A>G]). The other
      patient, heterozygous for position 2, had one heterozygous unaffected parent.
      Most parents were heterozygous for this base exchange, confirming the pattern of
      autosomal recessive inheritance for congenital IF deficiency. cDNA encoding GIF
      was mutated at base pair g.68 (A>G) and expressed in COS-7 cells. The apparent
      size, secretion rate, and sensitivity to pepsin hydrolysis of the expressed IF
      were similar to native IF. The allelic frequency of g.68A>G was 0.067 and 0.038
      in two control populations. This sequence aberration is not the cause of the
      phenotype, but is associated with the genotype of congenital IF deficiency and
      could serve as a marker for inheritance of this disorder.

PMID- 14695537
TI  - Pyrosequencing-based SNP allele frequency estimation in DNA pools.
AB  - Association screening involving numerous genetic markers is facilitated by the
      analysis of pooled DNA samples rather than individual samples. Several genotyping
      methods have shown high accuracy and precision of allele frequency estimation in
      pools. Here, we expand the validation of SNP allele frequency estimation in DNA
      pools using Pyrosequencing by analyzing 186 pools for three SNPs representing
      complex sequencing cases. The correlation coefficient between estimated and true
      allele frequencies ranged between 0.979 and 0.996 and tended to increase with
      pool size, whereas the difference between estimated and true allele frequencies
      was 2.37+/-0.11%, in post-PCR pools. The precision was 1.73%. Pool size had no
      significant effect on accuracy and precision. A comparison between post-PCR and
      pre-PCR pools showed that for pre-PCR pooling efforts to accurately quantify the
      genomic DNA samples to be pooled and subsequently amplified are critical. To
      conclude, Pyrosequencing can be used for allele frequency estimation in DNA pools
      of SNPs with complex sequencing scenarios with accuracy and precision values in
      ranges comparable with those of other SNP typing techniques. Considering the ease
      of use, short run and analysis times, and little instrument maintenance
      requirements, Pyrosequencing may even be a preferred option.

PMID- 14695538
TI  - Novel mutations in the Atlastin gene (SPG3A) in families with autosomal dominant
      hereditary spastic paraplegia and evidence for late onset forms of HSP linked to
      the SPG3A locus.
AB  - Hereditary spastic paraplegias (HSP) comprise a genetically and clinically
      heterogeneous group of neurodegenerative disorders characterised by progressive
      spasticity and hyperreflexia of the lower limbs. Autosomal dominant hereditary
      spastic paraplegia linked to the SPG3A locus on chromosome 14q11-21 accounts for
      approximately 10% of autosomal dominant hereditary spastic paraplegia (ADHSP). It
      is caused by mutations in the SPG3A gene encoding the protein atlastin. To date,
      only five disease-causing mutations in the SPG3A gene have been described. We
      analysed 13 SPG4-negative families for mutations in the SPG3A gene and identified
      a mutation in 38% (5/13). Two of the mutations are novel, c.481G>C (p.A161P) and
      c.740A>C (p.H247P). One of the novel mutations was found both in a family with
      early onset of symptoms and in a late onset family. Furthermore, we report on
      numerous polymorphisms detected in the SPG3A gene.

PMID- 14695539
TI  - Phenotype-genotype characterization of 10 families with severe a subunit factor
      XIII deficiency.
AB  - Factor XIII (FXIII) deficiency is a very rare severe autosomal bleeding disorder
      with a frequency of 1:2,000,000 in the general population and only a few patients
      have been genetically characterized so far. We report a phenotype-genotype
      characterization of 10 unrelated Iranian patients. Two FXIII (transglutaminase)
      activity assays showed no FXIII activity, except a conserved residual activity in
      patients receiving prophylactic substitution treatment. FXIII antigen
      concentrations measured by two immunoassays were comparable. Genotype
      characterization identified four novel mutations (2 missense and 2 small
      deletions) and two previously reported missense mutations in the FXIII A subunit
      gene (F13A). Molecular modeling was carried out to reveal the structural
      consequences of the missense mutations, that caused the replacement of an
      arginine residue involved in the formation of structurally important extensive
      hydrogen-bonded network. The replacements [c.320G>A (p.Arg77His) in the beta
      sandwich, c.868C>T (p.Arg260Cys), c.869G>A (p.Arg260His) and c.1236G>T
      (p.Arg382Ser) in the core domain] resulted in the loss or impairment of such H
      bonded network. Energy decomposition analysis demonstrated that this situation
      leads to the instability and perhaps to the incorrect folding of the A subunit,
      that would explain the development of severe FXIII deficiency.

PMID- 14695540
TI  - Detection of thirty novel FBN1 mutations in patients with Marfan syndrome or a
      related fibrillinopathy.
AB  - Marfan syndrome (MFS) is a disorder of the extracellular matrix caused by
      mutations in the gene encoding fibrillin-1 (FBN1). Recent studies have
      illustrated the variability in disease severity and clinical manifestations of
      MFS. Useful genotype-phenotype correlations have been slow to emerge. We screened
      57 unrelated patients with MFS or a Marfan-like phenotype using a combination of
      SSCP and/or DHPLC. We detected 49 different FBN1 mutations, 30 (62%) of which
      were novel. The mutations comprised 38 substitutions (78%), 10 deletions (20%),
      and one duplication (2%). There were 28 missense (57%), nine frameshift (18%),
      eight splice site (16%), and four nonsense mutations (8 %). Genotype-phenotype
      analysis revealed that patients with an identified FBN1 mutation were more likely
      to have ectopia lentis and cardiovascular complications compared to those without
      an identifiable mutation (relative risks of 4.6 and 1.9, respectively). Ectopia
      lentis was also found to be more prevalent in patients whose mutations involved a
      cysteine substitution (relative risk 1.6) and less prevalent in those with
      premature termination mutations (relative risk 0.4). In our hands, we achieved
      93% mutation detection for DHPLC analysis of patients who fulfilled the Ghent
      criteria. Further analysis of detailed clinical information and mutation data may
      help to anticipate the clinical consequences of specific FBN1 mutations.

PMID- 14695541
TI  - Variants in TNFRSF5 locus and association analysis with Hepatitis B virus (HBV)
      infection.
AB  - Human TNFRSF5, a key signaling molecule expressed by antigen-presenting cells of
      the immune system, might have associations with autoimmune diseases and various
      infectious diseases. In the present study, we screened single-nucleotide
      polymorphisms (SNPs) in TNFRSF5 and examined whether they are risk factors for
      persistent HBV infection or disease severity. We resequenced all 9 exons, the
      promoter and splicing regions of all introns for 186 Chinese individuals, and
      identified 11 SNPs. Haplotypes and their frequencies were estimated. The linkage
      disequilibrium (LD) pattern was also evaluated. Neutrality tests indicated that
      the variation pattern at TNFRSF5 locus departs from neutrality and may be
      maintained by positive selection or demography factors such as population growth.
      Three SNPs (g.53031T>C, g.54068T>C and g.64493A>G) were determined as haplotype
      tag SNPs (htSNPs). Furthermore, computer analyses indicated that sequences
      surrounding g.53031T>C and g.53824T>C were potential binding sites for
      transcription factors Sp1 and H4TF-2, respectively. We then genotyped these four
      SNPs for 603 persistent HBV infection patients and 384 spontaneously recovered
      subjects by PCR direct sequencing. No statistically significant associations were
      observed between any of the SNPs or haplotypes and persistent HBV infection or
      disease severity. The information from this study of the TNFRSF5 would be useful
      for genetic studies of other common diseases.

PMID- 14695542
TI  - Large deletions in the polycystic kidney disease 1 (PKD1) gene.
AB  - Since identification of the genes mutated in patients with Autosomal Dominant
      Polycystic Kidney Disease, PKD1 and PKD2, a large number of different germ line
      mutations in both genes have been found by conventional PCR-based mutation
      detection methods. Nevertheless, in approximately 40% of the PKD1 families the
      disease-causing mutation remains to be elucidated. Complex germ line
      rearrangements are often not detectable by these standard diagnostic techniques.
      To detect large deletions in the PKD1 gene we performed Field Inversion Gel
      Electrophoresis (FIGE) followed by Southern blot analysis with probes selected in
      the unique and in the reiterated region of this gene. Our analysis revealed 4
      deletions in 125 patients, indicating that large deletions in PKD1 are rare.
      Likely, patients with a deletion that also affects the neighbouring Tuberous
      Sclerosis Complex 2 (TSC2) gene will be diagnosed as patients with tuberous
      sclerosis. It was speculated that the exceptional polypyrimidine tract located in
      intron 21 and the small tract in intron 22, might play a role in the pathogenesis
      of ADPKD. Since this region is extremely difficult to amplify by PCR, we analysed
      the 5.8 kb BamHI fragment that contains the polypyrimidine tracts. We did not
      observe a disease-linked alteration although we detected two different rare
      variants either in PKD1 or in one of its homologues.

PMID- 14695543
TI  - Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese
      population.
AB  - In order to identify single nucleotide polymorphisms (SNPs) and haplotype
      frequencies of CYP3A4 in a Japanese population, the distal enhancer and proximal
      promoter regions, all exons, and the surrounding introns were sequenced from
      genomic DNA of 416 Japanese subjects. We found 24 SNPs, including 17 novel ones:
      two in the distal enhancer, four in the proximal promoter, one in the 5'
      untranslated region (UTR), seven in the introns, and three in the 3'-UTR. The
      most common SNP was c.1026+12G>A (IVS10+12G>A), with a 0.249 frequency. Four non
      synonymous SNPs, c.554C>G (p.T185S, CYP3A4(*)16), c.830_831insA (p.E277fsX8,
      (*)6), c.878T>C (p.L293P, (*)18), and c.1088 C>T (p.T363M, (*)11) were found with
      frequencies of 0.014, 0.001, 0.028, and 0.002, respectively. No SNP was found in
      the known nuclear transcriptional factor-binding sites in the enhancer and
      promoter regions. Using these 24 SNPs, 16 haplotypes were unambiguously
      identified, and nine haplotypes were inferred by aid of an expectation
      maximization-based program. In addition, using data from 186 subjects enabled a
      close linkage to be found between CYP3A4 and CYP3A5 SNPs, especially among the
      SNPs at c.1026+12 in CYP3A4 and c.219-237 (IVS3-237, a key SNP site for
      CYP3A5(*)3), c.865+77 (IVS9+77) and c.1523 in CYP3A5. This result suggested that
      CYP3A4 and CYP3A5 are within the same gene block. Haplotype analysis between
      CYP3A4 and CYP3A5 revealed several major haplotype combinations in the CYP3A4
      CYP3A5 block. Our findings provide fundamental and useful information for
      genotyping CYP3A4 (and CYP3A5) in the Japanese, and probably Asian populations.

PMID- 14695544
TI  - First report of a genetic polymorphism of the cytochrome P450 3A43 (CYP3A43)
      gene: identification of a loss-of-function variant.
AB  - In the present study, we report the first investigation of polymorphisms in the
      human CYP3A43 gene. A screening for sequence variations in the 5'-flanking and
      protein coding regions of the CYP3A43 gene was performed by a Polymerase Chain
      Reaction - Single Strand Conformational Polymorphism (PCR-SSCP) strategy, using
      DNA samples from 48 unrelated French individuals. Three polymorphisms in the
      coding region were identified, comprising two nucleotide substitutions, one
      silent (c.1047C>T) and one missense mutation (c.1018C>G/P340A), and a frame shift
      mutation (c.74delA), leading to a premature stop codon and, presumably, to a
      severely truncated protein. In order to evaluate the extent of the frame shift
      mutation in a larger population, 352 individuals were further genotyped. Thirty
      four samples (4.83%) were found to be heterozygous and one homozygous (0.14%) for
      the nucleotide deletion, which suggests that, although the potential significance
      of this polymorphism remains to be further evaluated, some individuals are
      deficient for CYP3A43 activity.

PMID- 14695547
TI  - Promises and problems of mesoscale materials chemistry or why meso?
AB  - Manipulation and control of chemical structures on the mesoscale has recently
      developed to a very promising and also aesthetically appealing area of chemistry.
      This concept article tries to integrate the views of two experts to delineate the
      specific principles, approaches, and the novel opportunities for chemistry that
      arise from the rational control of matter and functionality on that scale.

PMID- 14695548
TI  - Detection and amplification of chirality by helical polymers.
AB  - A unique feature of synthetic helical polymers for the detection and
      amplification of chirality is briefly described in this article. In sharp
      contrast to host-guest and supramolecular systems that use small synthetic
      receptor molecules, chirality can be significantly amplified in a helical
      polymer, such as poly(phenylacetylene)s with functional pendants, which enable
      the detection of a tiny imbalance in biologically important chiral molecules
      through a noncovalent bonding interaction with high cooperativity. The rational
      design of polymeric receptors can be possible by using chromophoric helical
      polymers combined with functional groups as the pendants, which target particular
      chiral guest molecules for developing a highly efficient chirality-sensing
      system. The chirality sensing of other small molecular and supramolecular systems
      is also briefly described for comparison.

PMID- 14695549
TI  - Synthesis of novel chiral and acentric coordination polymers by the reaction of
      zinc or cadmium salts with racemic 3-pyridyl-3-aminopropionic acid.
AB  - Under hydrothermal (solvothermal) reaction conditions chiral compounds 1, 2, and
      3 and one acentric compound 4 were obtained by the reaction of Zn(2+) or Cd(2+)
      with racemic 3-(3-pyridyl)-3-aminopropionic acid (rac-HPAPA). Compounds 1 and 2
      crystallized in chiral space group P2(1)2(1)2(1). At 105 degrees C, racemic 3
      pyridyl-3-aminopropionic acid (rac-HPAPA) reacted with Zn(ClO4)(2).6 H2O and
      dehydrogenated in situ to form the first chiral coordination polymer [Zn[(E)-3
      C(5)H4N-C(NH2)=CH-COO]]ClO4 (1) with a beta-dehydroamino acid. Beyond 120 degrees
      C, the reaction of rac-HPAPA with Zn(ClO4)(2).6 H2O deaminates in situ to form
      chiral coordination polymer [Zn[(E)-3-C5H4N-CH=CH-COO](OH)] (2). At relatively
      low temperatures (70 degrees C), the solvothermal reaction of Zn(NO3)(2).6 H2O
      with rac-HPAPA in methanol does not lead to any change in the ligand and results
      in the formation of a chiral (P2(1)2(1)2(1)) coordination polymer [Zn(papa)(NO3)]
      (3). The same reaction of Cd(ClO4)(2).6 H2O with HPAPA also does not lead to any
      change in ligand and results in the formation of noncentric (Cc) coordination
      polymer [Cd(papa)(Hpapa)]ClO4.H2O (4). The network topology of both 1 and 3 is
      10,3a, while 2 has a diamondoid-like (KDP-like, KDP=potassium dideuterophosphate)
      network. Particularly interesting from a topological perspective is that 4 has an
      unprecedented three-dimensional network. Compounds 1, 2, 3, and 4 are all second
      harmonic generation (SHG) active with 1 exhibiting the strongest response, while
      only 4 also displays good ferroelectric properties.

PMID- 14695550
TI  - A chiroptical molecular switch with distinct chiral and photochromic entities and
      its application in optical switching of a cholesteric liquid crystal.
AB  - Two new structurally related photoswitches are described, in which azobenzene
      photochromism is combined with the chirality of a 2,2'-dihydroxy-1,1'-binaphthyl
      unit. In system 1 the chiral binaphthyl moiety is bridged by a methylene tether,
      locking the biaryl chirality while in system 2 the biaryl core is unbridged and
      has considerable conformational flexibility. Both compound are capable of
      inducing cholesteric liquid crystalline phases and proved to be good
      photoswitches both in solution and in a liquid crystalline matrix. Compound 2 is
      capable of completely reversing the liquid crystalline chirality which is unique
      for a chiroptical molecular switch where the switching unit and the chiral moiety
      are separate entities.

PMID- 14695551
TI  - Highly efficient biomimetic total synthesis and structural verification of
      bistratamides E and J from Lissoclinum bistratum.
AB  - The interesting biological activities of heterocycle-containing cyclic peptide
      derived natural products, isolated from marine organisms over the past twenty
      years, have attracted the interest of many synthetic and natural products
      chemists. Bistratamides E-J, members of this class of natural products that were
      isolated very recently from Lissoclinum bistratum, exhibited cytotoxic activity
      against a human colon tumor (HCT-116) cell line. Here we report the first total
      syntheses of bistratamides E (1) and J (2) in overall yields of 19 and 34 %,
      respectively. The thiazole substructures have been synthesized by oxidation of
      their corresponding thiazoline substructures, which were obtained from cysteine
      containing peptides using a novel biomimetic approach wherein Val-Cys dipeptide
      units were converted to thiazolines by a bisphosphonium salt. The final
      macrocyclization was promoted efficiently using the combination of PyBOP and
      DMAP. This approach allows the use of readily available Fmoc-protected amino
      acids to make complex thiazole and oxazoline-containing natural products.

PMID- 14695552
TI  - A concave fluorescent sensor for anions based on 6-methoxy-1-methylquinolinium.
AB  - The ligand 2, in which three fluorogenic 6-methoxy-1-methylquinolinium fragments
      are appended to a mesityl platform, in MeCN forms 1:1 adducts with halides and
      other inorganic anions. (1)H NMR studies and molecular modelling indicate that 2
      provides a cavity for anion inclusion and establishes electrostatic interactions
      with the guest. Anion inclusion induces quenching of the fluorogenic fragments
      with an efficiency decreasing along the series Br(-)>>I(-)>NCS(-)>>Cl(-)>NO(3) (
      )>HSO(4) (-). The fluorimetric response of 2 to anions is orders of magnitude
      more sensitive than that of just 6-methoxy-1-methylquinolinium, ligand 1.

PMID- 14695553
TI  - Crystal, molecular and electronic structure of N,N'-diphenyl-N,N'-bis(2,4
      dimethylphenyl)-(1,1'-biphenyl)-4,4'-diamine and the corresponding radical
      cation.
AB  - Oxidation of N,N'-diphenyl-N,N'-bis(3-methylphenyl)-(1,1'-biphenyl)-4,4'-diamine
      (TPD, 1 a) and N,N'-diphenyl-N,N'-bis(2,4-dimethylphenyl)-(1,1'-biphenyl)-4,4'
      diamine (1 b) with SbCl(5) affords the corresponding radical cations
      quantitatively. The crystal and molecular structure of 1 b and [1 b]SbCl(6), the
      first tetraphenyl benzidene derivatives to be characterised crystallographically
      in both the neutral and radical cation states, reveal molecular parameters in
      agreement with the predictions made on the basis of DFT studies. Analysis of the
      NIR transition in the radical cations [1](+) (.) allows an estimate of the
      electronic coupling parameter V (1 a(+) (.) 3200 cm(-1); 1 b(+) (.) 3300 cm(-1)),
      the reorganisation energy lambda(1 a(+) (.) 7500 cm(-1); 1 b(+) (.) 7800 cm(-1)),
      and the linear coupling constant l (1 a(+) (.) 3100 cm(-1); 1 b(+) (.) 2700 cm(
      1)) of the symmetric mode.

PMID- 14695554
TI  - Modular solid-phase synthetic approach to optimize structural and electronic
      properties of oligoboronic acid receptors and sensors for the aqueous recognition
      of oligosaccharides.
AB  - This article describes the design and optimization of the first entirely modular,
      parallel solid-phase synthetic approach for the generation of well-defined
      polyamine oligoboronic acid receptors and fluorescence sensors for complex
      oligosaccharides. The synthetic approach allows an effective building of the
      receptor polyamine backbone, followed by the controlled diversification of the
      amine benzylic side chains. This approach enabled the testing, in a modular
      fashion, of the effect of different arylboronic acid units substituted with
      unencumbering para electron-withdrawing or electron-donating groups. The
      feasibility of this approach toward automated synthesis was also investigated
      with the assembly of a sublibrary of receptors by means of the Irori MiniKan
      technology. Several sublibraries of anthracene-capped sensors containing two or
      three arylboronic acids were synthesized, and their binding to a series of model
      disaccharides was examined in neutral aqueous media. The calculation of
      association constants by fluorescence titrations confirmed that subtle changes in
      the structures of the interamine spacers in the polyamine backbone can have a
      significant effect on the stability of the resulting complexes. Most importantly,
      this study led to the determination of the preferred electronic characteristics
      for the arylboronate units, and suggests that a new generation of receptors
      containing very electron-poor arylboronic acids could lead to a significant
      improvement of binding affinities.

PMID- 14695555
TI  - Zirconium-mediated cross-coupling of terminal alkynes and vinyl bromides:
      selective synthesis of cyclobutene and 1,3-diene derivatives.
AB  - A diastereoselective synthesis of 1,3-butadiene or cyclobutene derivatives by a
      zirconium-mediated reaction of alkenyllithium compounds and vinyl bromides is
      reported. The key steps involve the generation of zirconocene-alkyne complexes
      from haloalkenes and subsequent coupling with alkenyl bromides. Thus, formally
      the process supposes the cross-coupling reaction between a terminal alkyne and an
      alkenyl bromide. Moreover, the use of butyl vinyl ether instead of vinyl bromide
      as the unsaturated system allows an alternative access to different 1,3-butadiene
      regioisomers.

PMID- 14695556
TI  - Zirconium-mediated coupling reactions of amines and enol or allyl ethers:
      synthesis of allyl- and homoallylamines.
AB  - An easy and efficient zirconium-mediated synthesis of allylamines from simple
      amines and enol ethers is described. This strategy also allows the synthesis of
      amino alcohol derivatives containing a Z double bond in their structure when 2,3
      dihydrofuran is used. Simple conventional modification of these amino alcohols
      leads to 2-substituted piperidine derivatives. By applying this approach, a
      formal total synthesis of the alkaloid coniine is easily achieved from a
      protected butylamine. Finally, the zirconium-mediated reaction of amines and
      allyl phenyl ether furnishes homoallylamines or amino ethers depending on the
      structure of the starting amine.

PMID- 14695557
TI  - Synthesis and spectroscopic and electrochemical studies of novel benzo- or 2,3
      naphtho-fused tetraazachlorins, bacteriochlorins, and isobacteriochlorins.
AB  - Benzene- or 2,3-naphthalene-ring-expanded tetraazachlorins (TACs),
      tetraazabacteriochlorins (TABCs), and tetraazaisobacteriochlorins (TAiBCs) have
      been synthesized by using tetramethylsuccinonitrile as a source of hydrogenated
      sites. The derived compounds were characterized by using NMR spectroscopy, X-ray
      crystallography, electronic and magnetic circular dichroism (MCD) spectroscopy,
      and electrochemical and spectroelectrochemical methods. X-ray analysis revealed
      that the benzene-fused TAiBC deviates slightly from planarity at the hydrogenated
      sites as a result of the presence of sp(3) carbons, which prefer a nonplanar
      tetrahedral conformation. The spectral data were analyzed by using a band
      deconvolution technique. In the electronic absorption spectra of TAC and TABC
      species, the Q band splits into two intense components and smaller splittings
      were observed for the 2,3-naphthalene-fused derivatives relative to the benzo
      fused species. In contrast, in the case of TAiBCs, the Q band splitting was
      apparently not observed in absorption spectra, as expected from the C(2v)
      molecular symmetry. However, MCD signals of the Q band in TAiBCs showed Faraday B
      terms, implying that the accidental degeneracy of the LUMO and LUMO+1 was broken
      even for adjacently ring-fused species. Relative molecular orbital energies were
      estimated by using cyclic and differential pulse voltammetry. The first reduction
      potentials were close for TACs and TABCs, although those of TAiBCs shifted to
      more negative potentials. In contrast, although TABCs and TAiBCs exhibited
      similar first oxidation potentials, those of TACs appeared at more positive
      potentials. These properties were reproduced and rationalized by molecular
      orbital and configuration interaction calculations within the framework of the
      ZINDO/S Hamiltonian. DFT-level frequency calculations have succeeded in
      reproducing the IR spectra for low-symmetry tetraazaporphyrin (TAP) derivatives
      for the first time. The relationship between structures and spectral features is
      discussed.

PMID- 14695558
TI  - Acid-base sensors based on novel quinone-type dyes.
AB  - We present a detailed study on the acid-base behaviour of a family of
      "potentially antiaromatic" p-benzoquinonediimine ligands. These 12pi electron
      molecules can be considered as constituted of two chemically connected but
      electronically not conjugated 6pi-electron subunits. Upon successive protonation,
      "mono" and "double" cyanine-type chromophores are generated in solution and allow
      a precise and sensitive spectrophotometric detection. These molecules represent a
      new class of tunable quinones whose electronic and structural properties can be
      triggered by proton input, as established by a complete physico-chemical study
      involving a combination of potentiometric and spectrophotometric methods
      (absorption and emission).

PMID- 14695559
TI  - Polyoxotungstate photoinduced alkylation of electrophilic alkenes by
      cycloalkanes.
AB  - Alkyl radical obtained by irradiation of tetrabutylammonium decatungstate in
      acetonitrile in the presence of cycloalkanes (C5H10, C6H12, C7H14) are
      efficiently trapped by electrophilic alkenes (acrylonitrile,
      isopropylydenmalonitrile, isopropylydencyanoacetate) to give the corresponding
      alkylated aliphatic nitriles. The reaction can be carried out up to complete
      conversion of the alkene with reasonable (in most cases 60-65 %) yields. Addition
      of the radicals to the alkene is followed by electron transfer from reduced
      decatungstate regenerating the sensitizer (turn over number up to 60). Steady
      state measurements, EPR evidence, deuteration experiments and attempted
      intramolecular trapping of the adduct radical support the mechanistic proposal.

PMID- 14695560
TI  - Metal-induced tautomerization of p- to o-quinone compounds: experimental evidence
      from CuI and ReI complexes of azophenine and DFT studies.
AB  - Azophenine (7,8-diphenyl-2,5-bis(phenylamino)-p-quinonediimine, L(p)) reacts with
      [Cu(PPh3)4](BF4) or [Re(CO)(5)Cl] to yield the (Ph3P)(2)Cu(+) or [(OC)(3)ClRe]
      complex of the tautomeric form 7,8-diphenyl-4,5-bis(phenylamino)-o
      quinonediimine, L(o), as evident from structure determinations and from very
      intense metal-to-ligand charge transfer (MLCT) transitions in the visible region.
      Time-dependent DFT (TD-DFT) calculations on model complexes [(N intersection
      N)Re(CO)(3)Cl] confirm the spectroscopic results, showing considerably higher
      oscillator strengths of the MLCT transition for the o-quinonediimine complexes in
      comparison to compounds with N intersection N=1,4-dialkyl-1,4-diazabutadiene. The
      complexes are additionally stabilized through hydrogen bonding between two now
      ortho-positioned NHPh substituents and one fluoride of the BF(4) (-) anion (Cu
      complex) or the chloride ligand (Re complex). DFT Calculations on the model
      ligands p-quinonediimine or 2,5-diamino-p-quinonediimine and their ortho
      quinonoid forms with and without Li(+) or Cu(+) are presented to discuss the
      relevance for metal-dependent quinoproteins.

PMID- 14695561
TI  - Redox-controllable amphiphilic [2]rotaxanes.
AB  - With the fabrication of molecular electronic devices (MEDs) and the construction
      of nanoelectromechanical systems (NEMSs) as incentives, two constitutionally
      isomeric, redox-controllable [2]rotaxanes have been synthesized and characterized
      in solution. Therein, they both behave as near-perfect molecular switches, that
      is, to all intents and purposes, these two rotaxanes can be switched precisely by
      applying appropriate redox stimuli between two distinct chemomechanical states.
      Their dumbbell-shaped components are composed of polyether chains interrupted
      along their lengths by i) two pi-electron rich recognition sites-a
      tetrathiafulvalene (TTF) unit and a 1,5-dioxynaphthalene (DNP) moiety-with ii) a
      rigid terphenylene spacer placed between the two recognition sites, and then
      terminated by iii) a hydrophobic tetraarylmethane stopper at one end and a
      hydrophilic dendritic stopper at the other end of the dumbbells, thus conferring
      amphiphilicity upon these molecules. A template-directed protocol produces a
      means to introduce the tetracationic cyclophane, cyclobis(paraquat-p-phenylene)
      (CBPQT(4+)), which contains two pi-electron accepting bipyridinium units,
      mechanically interlocked around the dumbbell-shaped components. Both the TTF unit
      and the DNP moiety are potential stations for CBPQT(4+), since they can establish
      charge-transfer and hydrogen bonding interactions with the bipyridinium units of
      the cyclophane, thereby introducing bistability into the [2]rotaxanes. In both
      constitutional isomers, (1)H NMR and absorption spectroscopies, together with
      electrochemical investigations, reveal that the CBPQT(4+) ring is predominantly
      located on the TTF unit, leading to the existence of a single translational
      isomer (co-conformation) in both cases. In addition, a model [2]rotaxane,
      incorporating hydrophobic tetraarylmethane stoppers at both ends of its dumbbell
      shaped component, has also been synthesized as a point of reference. Molecular
      synthetic approaches were used to construct convergently the dumbbell-shaped
      compounds by assembling progressively smaller building blocks in the shape of the
      rigid spacer, the TTF unit and the DNP moiety, and the hydrophobic and
      hydrophilic stoppers. The two amphiphilic bistable [2]rotaxanes are
      constitutional isomers in the sense that, in one constitution, the TTF unit is
      adjacent to the hydrophobic stopper, whereas in the other, it is next to the
      hydrophilic stopper. All three bistable [2]rotaxanes have been isolated as green
      solids. Electrospray and fast atom bombardment mass spectra support the gross
      structural assignments given to all three of these mechanically interlocked
      compounds. Their photophysical and electrochemical properties have been
      investigated in acetonitrile. The results obtained from these investigations
      confirm that, in all three [2]rotaxanes, i) the CBPQT(4+) cyclophane encircles
      the TTF unit, ii) the CBPQT(4+) cyclophane shuttles between the TTF and DNP
      stations upon electrochemical or chemical oxidation/reduction of the TTF unit,
      and iii) folded conformations are present in which the CBPQT(4+) cyclophane,
      while encircling the TTF unit, interacts through its pi-accepting bipyridinium
      exteriors with other pi-donating components of the dumbbells, especially those
      located within the stoppers.

PMID- 14695563
TI  - Structure investigation of TiIV-BODOLates involved in the catalytic asymmetric
      reduction of ketones using catecholborane.
AB  - The complexes formed by the reaction of [Ti(OiPr)(4)] and bicyclo-octanediols
      (BODOLs) 1 and 2 (1:1) are useful as chiral catalysts in asymmetric reductions
      and were investigated by (1)H NMR spectroscopy and computational methods. A
      consistent picture emerged of head-to-tail dimers being kept together via a Ti-O
      Ti-O micro-oxo bridge similar to the Ti-tartrates but different from the
      corresponding Ti-BINOLates and Ti-TADDOLates.

PMID- 14695562
TI  - Solid-phase synthesis and screening of macrocyclic nucleotide-hybrid compounds
      targeted to hepatitis C NS5B.
AB  - A convergent strategy for the synthesis of cyclic nucleotide-hybrid molecules on
      controlled pore glass is reported. A major advantage of the approach is the lack
      of restrictions on the sequence and structural variation, allowing the
      incorporation of modified ribonucleosides (such as 2'-OMe-ribonucleotides), as
      well as threoninol derivatives. This methodology allows a fully automated
      assembly by means of standard phosphoramidite chemistry and is based on a
      recently published procedure for the preparation of cyclic oligodinucleotides in
      the DNA series (M. Smietana, E. T. Kool, Angew. Chem. 2002, 114, 3856-3859;
      Angew. Chem. Int. Ed. Engl. 2002, 41, 3704-3707). A library of potential cyclic
      hybrid inhibitor compounds targeting hepatitis C virus NS5B enzyme (the
      replicating polymerase of HCV) was generated by means of the parallel-pool
      strategy. Screening of the library revealed that cyclic hybrid c(C(OME)EthenodA)
      was a significant inhibitor of NS5B, with an IC(50) of 40 microM. Preliminary
      structure-activity studies of this lead compound are described.

PMID- 14695564
TI  - Mapping the stereochemistry and symmetry of tetracoordinate transition-metal
      complexes.
AB  - A continuous shape and symmetry study of tetracoordinate transition-metal
      complexes is presented, in an attempt to provide a systematic description of the
      stereochemistry of the metal coordination sphere in this important family of
      compounds. A tetrahedron/square-planar symmetry map has been developed, the main
      distortion paths of the ideal geometries are presented, and the applicability of
      a sawhorse shape measure is discussed. More than 13,000 structural data sets have
      been analyzed and the corresponding stereochemistries assigned from the values of
      their tetrahedral and square-planar symmetry measures. A good number of
      structures that are quite distant from the two ideal geometries can be adequately
      described as snapshots along the spread pathway for their interconversion, making
      use of the corresponding path deviation function. Further analysis of the
      structural data by metal electron configuration or by the denticity and
      conformation of the ligands provide general rules to describe the stereochemical
      preferences of tetracoordinate transition metal centers.

PMID- 14695565
TI  - Framework fluxionality of organometallic oxides: synthesis, crystal structure,
      EXAFS, and DFT studies on [[Ru(eta6-arene)]4Mo4O16] complexes.
AB  - Reactions of the molybdates Na(2)MoO4.2 H2O and (nBu(4)N)2[Mo2O7] with
      [[Ru(arene)Cl(2)](2)] (arene=C(6)H5CH3, 1,3,5-C6H3(CH3)(3), 1,2,4,5-C6H2(CH3)4)
      in water or organic solvents led to formation of the triple-cubane organometallic
      oxides [[Ru(eta(6)-arene)](4)Mo4O16], whose crystal and molecular structures were
      determined. Refluxing triple cubane [[Ru(eta(6)-C6H5CH3)](4)Mo4O16] in methanol
      caused partial isomerization to the windmill form. The two isomers of [[Ru(eta(6)
      C6H5CH3)](4)Mo4O16] were characterized by Raman and Mo K-edge X-ray absorption
      spectroscopy (XAS), both in the solid-state and in solution. This triple-cubane
      isomer was also used as a spectroscopic model to account for isomerization of the
      p-cymene windmill [[Ru(eta(6)-1,4-CH3C6H4CH(CH3)2)](4)Mo4O16] in solution. Using
      both Raman and XAS techniques, we were then able to determine the ratio between
      the windmill and triple-cubane isomers in dichloromethane and in chloroform.
      Density functional calculations on [[Ru(eta(6)-arene)](4)Mo4O16] (arene=C6H6,
      C6H5CH3, 1,3,5-C6H3(CH3)3, 1,4-CH3C6H4CH(CH3)2, C6(CH3)6) suggest that the
      windmill form is intrinsically more stable, provided the complexes are assumed to
      be isolated. Intramolecular electrostatic interactions and steric bulk induced by
      substituted arenes were found to modulate but not to reverse the energy
      difference between the isomers. The stability of the triple-cubane isomers should
      therefore be accounted for by effects of the surroundings that induce a shift in
      the energy balance between both forms.

PMID- 14695566
TI  - Selective synthesis and characterization of single-crystal silver
      molybdate/tungstate nanowires by a hydrothermal process.
AB  - Selective synthesis of uniform single crystalline silver molybdate/tungstate
      nanorods/nanowires in large scale can be easily realized by a facile hydrothermal
      recrystallization technique. The synthesis is strongly dependent on the pH
      conditions, temperature, and reaction time. The phase transformation was examined
      in details. Pure Ag(2)MoO(4) and Ag(6)Mo(10)O(33) can be easily obtained under
      neutral condition and pH 2, respectively, whereas other mixed phases of
      Mo(17)O(47), Ag(2)Mo(2)O(7,) Ag(6)Mo(10)O(33) were observed under different pH
      conditions. Ag(6)Mo(10)O(33) nanowires with uniform diameter 50-60 nm and length
      up to several hundred micrometers were synthesized in large scale for the first
      time at 140 degrees C. The melting point of Ag(6)Mo(10)O(33) nanowires were found
      to be about 238 degrees C. Similarly, Ag(2)WO(4), and Ag(2)W(2)O(7)
      nanorods/nanowires can be selectively synthesized by controlling pH value. The
      results demonstrated that this route could be a potential mild way to selectively
      synthesize various molybdate nanowires with various phases in large scale.

PMID- 14695567
TI  - A unique binaphthyl strapped iron-porphyrin catalyst for the enantioselective
      epoxidation of terminal olefins.
AB  - A new chiral binaphthyl-strapped iron-porphyrin 4 b that exhibits unprecedented
      catalytic activity toward the enantioselective epoxidation of terminal olefins
      was synthesized. Typical enantiomeric excesses (ee) of 90 % were measured with a
      maximum of 97 % for the epoxidation of styrene, whereas the turnover numbers
      (TON) averaged 16000.

PMID- 14695568
TI  - Ruthenium-catalyzed one-pot double allylation/cycloisomerization of 1,3
      dicarbonyl compounds leading to exo-methylenecyclopentanes.
AB  - The ruthenium-catalyzed one-pot double allylation/cycloisomerization of 1,3
      diketones and methyl acetoacetate gave exo-methylenecyclopentanes in moderate to
      good yields with high isomer selectivity. The double allylation step effectively
      proceeded in the presence of a Ru(II) precatalyst, [Cp*RuCl(cod)], in 1,2
      dichloroethane at 90 degrees C. The subsequent cycloisomerization was carried out
      upon addition of triethylsilane as a hydride source without purification of a 1,6
      diene intermediate. Detailed inspections of the reaction by (1)H NMR spectroscopy
      disclosed that triethylsilyl methyl ether plays an important role for the
      conversion of a ruthenium(IV) allyl complex formed in the double allylation step
      into a ruthenium(II) species required for the cycloisomerization.

PMID- 14695569
TI  - Quantitative evaluation of d-pi interaction in copper(I) complexes and control of
      copper(I)-dioxygen reactivity.
AB  - Crystal structures of the copper(I) complexes 1(X), 2, and 3 of a series of
      tridentate ligands L1(X), L2, and L3, respectively (L1(X): p-substituted
      derivatives of N,N-bis[2-(2-pyridyl)ethyl]-2-phenylethylamine; X=H, Me, OMe, Cl,
      NO(2); L2: N,N-bis[2-(2-pyridyl)ethyl]-2-methyl-2-phenylethylamine; L3: N,N-bis[2
      (2-pyridyl)ethyl]-2,2-diphenylethylamine) were solved to demonstrate that all the
      copper(I) complexes involve an eta(2) copper-arene interaction with the phenyl
      ring of the ligand sidearm. The Cu(I) ion in each complex has a distorted
      tetrahedral geometry consisting of the three nitrogen atoms (one tertiary amine
      nitrogen atom and two pyridine nitrogen atoms) and C(1)-C(2) of the phenyl ring
      of ligand sidearm, whereby the Cu-C distances of the copper-arene interaction
      significantly depend on the para substituents. The existence of the copper-arene
      interaction in a nonpolar organic solvent (CH(2)Cl(2)) was demonstrated by the
      observation of an intense MLCT band around 290 nm, and the magnitude of the
      interaction was evaluated by detailed analysis of the (1)H and (13)C NMR spectra
      and the redox potentials E(1/2) of the copper ion, as well as by means of the
      ligand-exchange reaction between the phenyl ring and CH(3)CN as an external
      ligand. The thermodynamic parameters DeltaH(o) and DeltaS(o) for the ligand
      exchange reaction with CH(3)CN afforded a quantitative measure for the energy
      difference of the copper-arene interaction in the series of copper(I) complexes.
      Density functional studies indicated that the copper(I)-arene interaction mainly
      consists of the interaction between the d(z(2) ) orbital of Cu(I) and a pi
      orbital of the phenyl ring. The copper(I) complexes 1(X) reacted with O(2) at -80
      degrees C in CH(2)Cl(2) to give the corresponding (micro-eta(2):eta(2)
      peroxo)dicopper(II) complexes 4, the formation rates k(obs) of which were
      significantly retarded by stronger d-pi interaction, while complexes 2 and 3,
      which exhibit the strongest d-pi interaction showed significantly lower
      reactivity toward O(2) under the same experimental conditions. Thus, the d-pi
      interaction has been demonstrated for the first time to affect the copper(I)
      dioxygen reactivity, and represents a new aspect of ligand effects in copper(I)
      dioxygen chemistry.

PMID- 14695570
TI  - Selective adsorption of polychlorinated dibenzo-p-dioxins and dibenzofurans by
      the zeosils UTD-1, SSZ-24, and ITQ-4.
AB  - Zeosils are microporous solids with a pure silica framework. Due to their
      hydrophobic properties, zeosils are ideal host materials for the adsorption of
      hydrophobic guest molecules. We tested zeosils with different pore diameters (UTD
      1, SSZ-24 and ITQ-4 as well as CIT-5) for the selective adsorption of the
      polychlorinated dibenzo-p-dioxins and dibenzofurans. This group of highly toxic
      substances contains 210 congeners that possess similar chemical properties, but
      differ in their size and shape. In the experiment, polychlorinated dibenzo-p
      dioxins and dibenzofurans were extracted from fly ash of a waste incinerator,
      adsorbed on amorphous silica, then thermally desorbed and flushed over a
      sequential arrangement of the zeosils at elevated temperature by a stream of
      nitrogen. ITQ-4 with the smallest pore diameter was placed first, followed by SSZ
      24 and, finally, by UTD-1 with the largest pore diameter. After the experiment,
      the zeosils were analysed for their contents of the different congeners. The
      results show that the sorption of the congeners occurs selectively and that it is
      governed by the size and the shape of the dioxin molecules, which in turn depend
      on the number of chlorine atoms and the pattern of chlorine substitution
      (regioisomers). Geometrical reasoning as well as molecular dynamics calculations
      on the zeosil structures and on the dioxin molecules were helpful in
      rationalising the results. This work represents an especially complex case of the
      molecular sieving effect and may lead to a selective on-line monitoring of the
      concentrations of dioxin molecules in waste gases of industrial combustion
      processes. The size- and shape-selective sorption of dioxin molecules may also
      bear some resemblance to the molecular recognition process that occurs in nature
      at the aryl hydrocarbon receptor.

PMID- 14695571
TI  - Theoretical insights into the mechanism for thiol/disulfide exchange.
AB  - The mechanism for thiol/disulfide exchange has been studied with high-level
      theoretical calculations. Free energies, transition structures, charge densities,
      and solvent effects along the reaction pathway have been determined for the first
      time. Mechanistic results agree with experimental data, and support the idea that
      the thiolate is the reacting species and that the reaction indeed proceeds
      through an uncomplicated S(N)2 transition state. The transition structures have
      the charge density evenly concentrated in the attacking and leaving sulfur atoms.
      The charge densities allow us to rationalize the solvent effects. As transition
      structures have the charge density more widely distributed than reactants,
      hydrophobic environments catalyze the reaction. The effect can be so dramatic
      that disulfide exchange inside the active site of ribonucleotide reductase is
      estimated to be catalyzed 10(3) times faster than the reaction in water. It was
      also found that attack by thiol is much faster than previously assumed, if
      mediated through water chains. Although the present results, as well as
      experimental data, still suggest that thiolate is the main reaction species,
      water-mediated thiol attack is almost kinetically competitive, and can eventually
      become competitive under specific experimental conditions.

PMID- 14695572
TI  - Chiral iridium [corrected] xyliphos complexes for the catalytic imine
      hydrogenation leading to the metolachlor herbicide: isolation of catalyst
      substrate adducts.
AB  - Iridium complexes relevant to the catalytic enantioselective hydrogenation of 2
      methyl-6-ethylphenyl-1'-methyl-2'-methoxyethylimine (MEA-imine, 1) in the
      Syngenta Metolachlor (3) process were prepared and characterized. Reaction of the
      diphosphane (S)-1-[(R)-2-(diphenylphosphanyl)ferrocenyl]ethyldi(3,5
      xylyl)phosphane ((S)-(R)-Xyliphos, (S)-(R)-4) with [Ir(2)(micro-Cl)(2)(cod)(2)]
      (cod=1,5-cyclooctadiene) afforded [Ir(Cl)(cod)[(S)-(R)-4]] (7), which reacted
      with AgBF(4) to form [Ir(cod)[(S)-(R)-4]]BF(4) (8). Complexes 7 and 8 reacted
      with iodide to yield [Ir(I)(cod)[(S)-(R)-4]] (9). When 9 was treated with one and
      two equivalents of HBF(4), two isomers of the cationic Ir(III) iodo hydrido
      complex [Ir(I)(H)(cod)[(S)-(R)-4]]BF(4) were solated (10 and 11, respectively).
      Complex 9 was oxidized with one equivalent of I(2) to give the iodo-bridged
      dinuclear species [Ir(2)I(2)(micro-I)(3)[(S)-(R)-4](2))]I (12). [Ir(2)(micro
      Cl)(2)(coe)(4)] (coe=cyclooctene) reacted with (S)-(R)-4 to yield the chloro
      bridged dinuclear complex [Ir(2)(micro-Cl)(2)[(S)-(R)-4](2)] (13). Complexes 7-12
      were structurally characterized by single-crystal X-ray diffraction and tested as
      single-component catalyst precursors for enantioselective hydrogenation of MEA
      imine. Complex 10 and dinuclear complex 12 gave the best catalytic results.
      Efforts were also directed at isolating substrate- or product-catalyst adducts:
      Treatment of 8 with 2,6-dimethylphenyl-1'-methyl-2'-methoxyethylimine (DMA-imine,
      14, a model for 1) under H(2) allowed four isomers of [Ir(H)(2)[(S)-(R)
      4](14)]BF(4) (18-21) to be isolated. These analytically pure isomers were fully
      characterized by 2D NMR techniques. X-ray structural analysis of an Ir(I)-imine
      adduct, namely, [Ir(C(2)H(4))(2)(14)]BF(4) (25), which was prepared by reacting
      [IrCl(C(2)H(4))(4)] with [Ag(14)(2)]BF(4) (16), confirmed the kappa(2)
      coordination mode of imine 14.

PMID- 14695573
TI  - Nanocage encapsulation of two ortho-carborane molecules.
AB  - Bowl-shaped C-methylcalix[4]resorcinarene forms a 1:1 ball-and-socket
      nanostructure with o-carborane through two endo-cavity BC-H...pi hydrogen bonds.
      In the presence of 4',2:6,4"-terpyridine, two of these nanostructures are held
      together by four terpyridines through sixteen OH...N hydrogen bonds, completely
      shrouding two carboranes.

PMID- 14695574
TI  - Substituent-dependent reactivity in the photodimerization of N-substituted
      dibenz[b,f]azepines.
AB  - The photoprocesses of a series of N-substituted dibenz[b,f]azepines
      (iminostilbenes) were studied by absorption and emission spectroscopy, by laser
      flash photolysis, and by preparative irradiation with NMR analysis. In solutions,
      2pi+2pi photodimers of N-cyano and N-acyl dibenzazepines are formed via the
      triplet state upon acetone- or benzophenone-sensitized energy transfer. T-T
      absorption spectra were measured and absorption coefficients were determined. The
      triplet energy transfer is equally efficient for N-alkyl dibenzazepines, which do
      not dimerize. Excited states of npi* character in the latter cases are discussed
      to rationalize the different reactivities. In spite of negligible intersystem
      crossing of 21 dibenzazepine derivatives, photodimers of N-acyl and N-cyano
      dibenzazepines are formed upon direct excitation in concentrated solutions (0.01
      0.1 mol dm(-3)) as well as in the solid state. A selective anti-configuration of
      the photodimers was found throughout.

PMID- 14695575
TI  - Highly enantioselective ruthenium-catalyzed reduction of ketones employing
      readily available Peptide ligands.
AB  - Highly efficient and selective catalysts for the asymmetric reduction of aryl
      alkyl ketones under hydrogen-transfer conditions (2-propanol) were obtained by
      combining a novel class of pseudo-dipeptide ligands with [[RuCl(2)(p
      cymene)](2)]. A library of 36 dipeptide-like ligands was prepared from N-Boc
      protected alpha-amino acids and the enantiomers of 2-amino-1-phenylethanol and 1
      amino-2-propanol. The catalyst library was evaluated with the reduction of
      acetophenone and excellent enantioselectivity of 1-phenylethanol was obtained
      with several of the novel catalysts. A ligand based on the combination of N-Boc-L
      alanine and (S)-1-amino-2-propanol (ligand A-(S)-4) was found to be particular
      effective. When the situ formed ruthenium complex of this ligand was employed as
      the catalyst in the hydrogen-transfer reaction of various aryl alkyl ketones, the
      corresponding alcohol products were achieved in excellent enantioselectivity (up
      to 98 % ee).

PMID- 14695576
TI  - Formamidine ureas as tunable electrophiles.
AB  - Formamidine urea compounds exchange imine fragments with primary nitrogen
      nucleophiles, allowing the preparation of a variety of derivatives from a single
      precursor. The reactivities of these species are governed primarily by the
      electron-donating power of the substituents and are tunable over a range of
      >10(3) in first-order rates of hydrolysis.

PMID- 14695579
TI  - Penetration of muscles by branches of the mandibular nerve: a possible cause of
      neuropathy.
AB  - We carried out detailed dissections of the branches of the mandibular nerve and
      muscles innervated by these branches to investigate their positional
      relationships. We made the following observations: 1) small branch of the
      auriculotemporal nerve penetrated the lateral pterygoid muscle; 2) the entire
      lingual nerve penetrated the medial pterygoid muscle; and 3) branch of the
      mylohyoid nerve penetrated the mylohyoid muscle and communicated with the
      submandibular ganglion. No detailed descriptions of these nerve branches have
      been reported previously. The existence of these nerve branches that penetrate
      muscles might result in the neuralgic pain in the trigeminal region when such
      pain is of unknown origin.

PMID- 14695580
TI  - Main trunk of the left coronary artery: anatomic study of the parameters of
      clinical interest.
AB  - The objective of this study was to analyze in one single series all the
      characteristics of the main trunk of the left coronary artery (MT) that may be of
      use in the diagnosis and treatment of its pathologies. One-hundred human hearts
      from autopsies were used. The average age of the sample studied was 63.15 years
      +/- 18.76 (range = 17-94 years). The heart was removed after resection of the
      costosternum and placed in 10% formaldehyde. With gradual separation and
      retraction of the myocardial fasciculi the MT was exposed. The length of the MT,
      the luminal diameter of the MT at its midpoint, and the luminal diameter of the
      left coronary orifice were measured with a caliper. The angle of division between
      the anterior interventricular and circumflex branches was also measured, and the
      number of terminal branches originating from the MT was recorded. In four cases,
      there was no MT and the anterior interventricular and circumflex branches
      originated directly from the left aortic sinus. The average length of the MT was
      10.8 +/- 5.52 mm (range = 2-23 mm); the average diameter at its midpoint was 4.86
      +/- 0.80 mm; and there was no significant difference noted between the midpoint
      diameter of the MT and the diameter of the left coronary orifice. The most
      frequent type of division of the MT was bifurcation (62%); in 38% of cases the MT
      divided into three or more branches. An average value of 86.7 +/- 28.8 degrees
      was obtained for the angle of division of the terminal branches of the MT (range
      = 40-165 degrees ). There was a positive correlation between the length of the MT
      and the angle of division of its terminal branches, with the longest MTs having
      the largest angle of division.

PMID- 14695581
TI  - Determination of the width of the presacral space on magnetic resonance imaging.
AB  - Presacral space enlargement may be the first sign of certain diseases. The normal
      width of the presacral space has not been widely investigated and in all previous
      studies was calculated from lateral radiographs obtained at barium enema
      examination. Our study determined the normal width of the presacral space on MRI
      and investigated a possible difference between men and women. The width of the
      presacral space was measured retrospectively from sagittal T2-weighted MR images
      of 193 patients (87 males; 106 females, aged 18-83 years). Presacral space width
      was measured separately for S1, S2, and S3 vertebral levels from the anterior
      surface of the vertebral bodies to the closest part of the posterior wall of the
      rectum. Differences between male and female subjects were analyzed by t-tests.
      Normal mean widths of the presacral space in men and women were 16.2 mm and 11.9
      mm for S1, 14.9 mm and 11.2 mm for S2, and 13.0 mm and 10.6 mm for S3,
      respectively. Measurements of the presacral space width in men were significantly
      larger than in women at all three levels (P < 0.001 for S1, P < 0.001 for S2, P =
      0.006 for S3). In summary, the presacral space width measured on MRI was found to
      be significantly larger in the male than in the female population.

PMID- 14695582
TI  - Internal anal sphincter: an anatomic study.
AB  - The anatomy of the internal anal sphincter and surrounding structures was
      investigated in 24 cadavers using a surgical microscope (6-25 x magnification).
      An understanding of the anatomy of the internal anal sphincter is helpful in
      avoiding complications during surgical procedures in the anorectal region. The
      external anal sphincter was composed of three ellipsoid rings of skeletal muscle
      (subcutaneous, superficial, and deep) that encircle the anal canal; in contrast,
      we found that the internal anal sphincter was composed of flat rings of smooth
      muscle bundles stacked one on top of the other, like the slats of a Venetian
      blind. In each anal canal, the average number of ring-like slats observed was
      26.33 +/- 2.93 (range = 20-30) and each was covered by its own fascia. The smooth
      muscle fibers and fascia coalesced at three equidistant points around the anal
      canal to form three columns that extended distally into the lumen and differed in
      form from the other anal columns. When viewed from an anterior position, the
      columns were located anteriorly at the observer's right (5 o'clock position),
      posteriorly at the right (1 o'clock position), and laterally at the left (9
      o'clock position). This heretofore unreported anatomy of the internal anal
      sphincter may play an important role in closing off the lumen of the anal canal
      and maintaining bowel continence.

PMID- 14695583
TI  - Radial nerve in the radial tunnel: anatomic sites of entrapment neuropathy.
AB  - Common anatomical structures that can lead to radial nerve entrapment in the
      radial tunnel (radial tunnel syndrome) were studied in 46 embalmed cadaveric
      upper limbs. After dissecting the radial tunnel, we investigated: the radial
      nerve and its division into superficial and deep (DBRN) branches; the course of
      the DBRN in relation to the extensor carpi radialis brevis (ECRB) muscle; the
      presence of fat; fibrous adhesions between the anterior radiohumeral joint
      capsule and the DBRN; the nature of the superomedial margin of the ECRB; vascular
      arcades of the radial recurrent vessels; and the superior and inferior borders of
      the superficial layer of the supinator muscle. The locations of some of these
      structures were measured in reference to two fixed points: the radiohumeral joint
      line and a line joining the tips of medial and lateral epicondyles of humerus.
      Near the radiohumeral joint, fibrous adhesions were observed between the DBRN and
      underlying capsule in 23/46 (50%) cases; vascular arcades of the radial recurrent
      vessels were found in 33/46 (72%) cases; the superomedial margin of the ECRB was
      tendinous in 36/46 (78%) instances; the superior border of the superficial layer
      of the supinator muscle was noted to be tendinous (arcade of Frohse) in 40/46
      (87%) specimens, and the inferior border of the superficial layer of the
      supinator muscle was tendinous in 30/46 (65%) cases. These anatomical features in
      the radial tunnel are significant enough to lead to entrapment neuropathy of the
      radial nerve.

PMID- 14695584
TI  - One-third, two-thirds: relationship of the radial nerve to the lateral
      intermuscular septum in the arm.
AB  - The radial nerve penetrates the lateral intermuscular septum of the arm before
      dividing into deep and superficial branches. It may be encountered in both
      anterior and posterior approaches to the humerus. An ability to accurately
      predict the point at which the nerve pierces the septum would be valuable during
      surgery in the arm, and would facilitate planning an approach to exploring the
      radial nerve after fractures of the distal humeral shaft. It would, in
      particular, make minimally invasive surgical techniques less dangerous. We
      dissected 20 cadaver upper limbs to establish whether the radial nerve enters the
      anterior compartment of the arm at a predictable level. We found that in almost
      every case the radial nerve entered the anterior compartment at a point within 5
      mm of the junction of the distal and middle thirds of a line joining the lateral
      epicondyle of the humerus to the most lateral point of the acromion process of
      the scapula. This has not previously been described, and we believe is a useful
      aide-de-memoir to predicting the level at which the radial nerve penetrates the
      lateral intermuscular septum.

PMID- 14695585
TI  - Tensile properties of fresh human calcaneal (Achilles) tendons.
AB  - The purpose of this study was to measure the tensile properties of fresh human
      calcaneal (Achilles) tendons. Twenty fresh cadaveric (age range = 57-93 years)
      bone-Achilles tendon complexes were harvested within 24 hr postmortem. The
      calcaneus together with 15 cm of the Achilles tendon extending proximally from
      the insertion on the calcaneus was clamped and biomechanically tested. Each
      tendon was firmly fixed in clamps in an MTS Systems Corporation MTS testing
      machine and tension was applied at a displacement rate of 8 cm per minute until
      the tendon failed. The tensile force and tensile strain (as measured using an
      extensometer) were recorded and plotted using onboard software. The narrow age
      range of our donors prevented any meaningful correlation between age and tensile
      properties; however, the results showed that: 1) the average ultimate tensile
      strength (UTS) of the human Achilles tendon was 1189 N (range = 360-1,965), 2)
      there was a correlation between left and right legs for UTS, 3) there was a
      correlation between left and right legs in regard to cross sectional area, and 4)
      there was no correlation between UTS and cross-sectional area.

PMID- 14695586
TI  - Amputation through the hip joint during the pre-anaesthetic era.
AB  - Even to the present day, hip disarticulation is one of the most radical
      orthopaedic operations. First carried out on the Continent in 1774 and in Britain
      in 1779, this procedure was only deemed necessary in circumstances where death
      was otherwise inevitable. George James Guthrie claimed to have undertaken the
      first amputation through the hip joint in which the patient survived. We describe
      some of these cases from the pre-anaesthetic surgical literature in which
      amputation through the hip joint was undertaken, and we comment on the surgical
      techniques used. This information is complemented by the views of certain
      authorities on this procedure. Many surgeons during the first half of the 19th
      century, including Guthrie, sought alternative surgical operations to hip joint
      disarticulation. The removal of the head and neck of the femur was far less
      traumatic than disarticulation through the hip joint, and proved an extremely
      effective alternative procedure for lesions involving the proximal part of the
      femur where there was any possibility that the limb could be saved.

PMID- 14695587
TI  - Effect of lithotomy positions on strain of the obturator and lateral femoral
      cutaneous nerves.
AB  - The purpose of this study was to determine if various lithotomy positions
      increase strain on the obturator and lateral femoral cutaneous nerves in fresh
      adult cadavers. A static load cell was used to record strain changes of the
      obturator and lateral femoral cutaneous nerves in the pelvis and anterior thigh
      when the lower limbs were placed in three sets of positions of varying hip
      abduction and flexion. The means of the strain measurements, which were measured
      in grams in all positioning angles were compared to the baseline 0 degrees
      measurements. Analysis of variance was calculated for the differences. Flexion of
      the hip did not increase strain on either nerve. Abduction to 30 degrees or 45
      degrees increased strain by more than 30 g on the obturator nerve (P < 0.05) but
      not the lateral femoral cutaneous nerve. The addition of 45 degrees or more of
      flexion to abduction negated the strain increase on the obturator nerves seen
      with abduction alone. Nerve strain >30 g has been associated consistently with
      nerve dysfunction, disrupting axonal transmission, and causing structural neural
      damage. Our findings suggest that concomitant hip flexion should be used when
      placing anesthetized patients in a lithotomy position that includes abduction of
      the lower limbs to >30 degrees to decrease the risk for perioperative neuropathy
      of the obturator nerve.

PMID- 14695588
TI  - Pes anserinus: layered supportive structure on the medial side of the knee.
AB  - The pes anserinus is composed of a combination of tendinous insertions of the
      sartorius, gracilis and semitendinosus muscles. Precise knowledge of the
      structures on the medial side of the knee and the relationships between fascia
      and tendons is critical for diagnosis, surgery, and the development of improved
      operative procedures of the knee. To obtain precise data on the layered
      structures associated with the fascia cruris on the medial side of the knee and
      the fibrous bundles attached to them, we dissected nine legs of five adult
      cadavers. We observed a superficial longitudinal fibrous bundle on the
      superficial surface of the sartorius and a deep longitudinal fibrous bundle on
      the aponeurotic membrane covering the tendon of the gracilis muscle. The distal
      parts of the tendons of the gracilis and semitendinosus were found to have
      aponeurotic membranes, and these membranes were fused with the fascia cruris.
      These two longitudinal fibrous bundles and the aponeurotic membranes from the
      gracilis and semitendinosus tendons fused with the fascia cruris, and a small
      tendinous expansion from the semimembranosus muscle fused with the aponeurotic
      membrane from the semitendinosus tendon and tibial collateral ligament as well as
      the fascia covering the medial head of the gastrocnemius and fascia cruris. Based
      on the considerable tension from the sartorius, gracilis, semitendinosus,
      semimembranosus and gastrocnemius muscles, these bundles, membranes, and muscles
      may act as a complex tensor fasciae cruris muscle and play a significant role as
      stabilizers of the medial side of the knee joint in the upright posture.

PMID- 14695589
TI  - Micro-venous valves in the superficial veins of the human lower limb.
AB  - It is commonly believed that venous valves are not present in veins smaller than
      2 mm in diameter. Venous valves, however, have been identified recently in small
      veins in several regions of the body. This study was undertaken to determine the
      size distribution of venous valves in the human lower limb micro-venous
      circulation. Vascular casts were made from six adult lower limbs and the sampled
      areas were viewed by scanning electron microscopy. In total, 2,376 valves were
      identified from 410 cm(3) of subcutaneous tissue. The vast majority (94%) of the
      valves were in veins less than 300 microm in luminal diameter, with 65% of the
      valves present in venous channels less than 100 microm in luminal diameter. The
      smallest valves identified were present in venous channels 18 microm in diameter.
      All valves were bicuspid and often associated with a tributary. Endothelial cells
      on the vein wall not associated with a valve were fusiform and arranged parallel
      to the long axis of the vessel, however, the endothelial cells on the luminal and
      valve sinus surfaces of the cusp were more polyhedral in shape and showed no
      obvious pattern of alignment. This study provides direct evidence to show that
      small superficial veins of the human lower limb do contain abundant venous valves
      and, for the first time, shows that the majority of these valves are present
      within venous channels less than 100 microm in luminal diameter.

PMID- 14695590
TI  - Unusual variant of the extensor carpi radialis brevis muscle: a case report.
AB  - A variation of the extensor carpi radialis brevis muscle (ECRB) origin was
      discovered during a cadaveric dissection. The identified ECRB originated from the
      fascia/tendon of the extensor digitorum communis (EDC), without any of its origin
      at the usual location on the lateral epicondyle. The ECRB tendon inserted onto
      the third metacarpal base. A branch of the posterior interosseous nerve
      innervated the ERCB. This is the first report of an ECRB originating from the EDC
      fascia/tendon. This unique variation of the ECRB origin may be of clinical
      interest, especially in the treatment of lateral epicondylitis (tennis elbow).

PMID- 14695591
TI  - Muscle variations and abnormal branching and course of the ulnar nerve in the
      forearm and hand.
AB  - During dissection of the right forearm of a 27-year-old female cadaver,
      variations in the form and insertion of the palmaris longus muscle were observed.
      The tendon of the palmaris longus muscle, which demonstrated a centrally placed
      belly, split into two tendons: one inserted into the palmar aponeurosis and the
      other into the proximal part of the flexor retinaculum. Additionally, we found an
      accessory muscle extending between the flexor retinaculum and the tendon of the
      abductor digiti minimi muscle. This accessory muscle was located deep to the
      ulnar artery but superficial to the superficial and deep branches of the ulnar
      nerve at the wrist. Finally, an aberrant branch of the ulnar nerve was identified
      in the forearm; it traveled distally alongside the ulnar artery and in the palm
      demonstrated communications with common palmar digital nerves from the ulnar and
      the median nerves. No variations were observed in the contralateral upper limb.

PMID- 14695592
TI  - Altered course of the right testicular artery.
AB  - An unusual course of the right testicular artery was observed during routine
      dissection of the posterior abdominal wall of a 60-year-old male cadaver. It
      arose from the abdominal aorta, inferior and posterior to the origin of the right
      renal artery, and passed posterior to the inferior vena cava and right renal
      vein; it then arched anterior to the inferior pole of the right kidney and
      descended anterior to the psoas major muscle, crossing anterior to the
      genitofemoral nerve, ureter and the proximal part of the external iliac artery.
      Finally, it passed to the deep inguinal ring and through the inguinal canal to
      enter the spermatic cord with the other constituents. The left testicular artery
      arose from the abdominal aorta about 1 cm higher than the right testicular artery
      and followed a normal course. The embryologic basis and clinical importance of
      this case are discussed.

PMID- 14695593
TI  - Novel collateral connecting the external and internal carotid arteries.

PMID- 14695594
TI  - Evaluation of computer-aided instruction in the medical gross anatomy curriculum.
AB  - A two-year study was conducted to provide summative evaluations of web-based
      computer-aided instruction (CAI) specifically designed to supplement the
      laboratory dissections in the medical human anatomy course. Utilization of CAI
      was analyzed using server statistics, student surveys and network login tables.
      There was a significant increase in server requests for CAI over the period of
      the course in both years of the study. In general, student surveys corresponded
      with the login data for individual students, although several discrepancies
      showed limitations of the respective methodologies. When course examination
      scores were compared to the number of CAI logins for individual students, there
      were statistically significant direct correlations between exam grades and
      frequency of CAI use. Our findings illustrate the value of combining server
      statistics with user surveys for evaluations of CAI as an effective supplement
      for student learning in the anatomy curriculum.

PMID- 14695600
TI  - Quantum mechanics and chemistry: the relevance of nonlocality and entanglement
      for molecules.

PMID- 14695601
TI  - Binary superlattices of nanoparticles: self-assembly leads to "metamaterials".

PMID- 14695602
TI  - Bioinspired molecular design of light-harvesting multiporphyrin arrays.
AB  - Recent progress in fundamental studies on multiporphyrin arrays has provided
      structural parameters for the molecular design of artificial light-harvesting
      antennae which mimic the wheel-like antenna complexes of photosynthetic purple
      bacteria. Covalent and noncovalent approaches have been employed for the
      construction of artificial light-harvesting multiporphyrin arrays. Such arrays
      are categorized into ring-shaped, windmill-shaped, star-shaped, and dendritic
      architectures. In particular, dendritic multiporphyrin arrays have been proven to
      be promising candidates for both providing a large absorption cross-section and
      enabling the vectorial transfer of energy over a long distance to a designated
      point. Such molecular and supramolecular systems are also expected to be potent
      components for molecular electronics and photonic devices.

PMID- 14695603
TI  - Comments on recent achievements in biomimetic organic synthesis.
AB  - The appealing beauty of the routes that Nature uses to build natural products is
      breath taking and the quest for laboratory syntheses that mimic these routes is
      longstanding. Since Robert Robinson introduced the concept of biomimetic
      synthesis in 1917, debates have been conducted about the participation of
      specific enzymes in every step of the biogenesis of every class of natural
      product. The successful synthesis of many natural products often follows routes
      analogous to processes that occur in the living cell with minimum enzyme
      participation. It should not be concluded, however, that we are only able to
      imitate biogenetic processes in which enzymes are not involved. Perhaps the most
      appealing facet of a biomimetic strategy is that it pursues the development of
      synthetic methodology inspired by biogenesis, even if the mimicked biogenetic
      route is only hypothetical. Improved biogenetic syntheses could be brought about
      by artificial enzymes that catalyze specific transformations.

PMID- 14695604
TI  - Synthesis and reactivity of a 1,8-bis(methylium)naphthalenediyl dication.

PMID- 14695605
TI  - NMR spectroscopic determination of the solution structure of a branched nucleic
      acid from residual dipolar couplings by using isotopically labeled nucleotides.

PMID- 14695606
TI  - A neutral 3D copper coordination polymer showing 1D open channels and the first
      interpenetrating NbO-type network.

PMID- 14695607
TI  - A tetraguanidinium ligand binds to the surface of the tetramerization domain of
      protein P53.

PMID- 14695608
TI  - Dynamics of ordered-domain formation of DNA fragments on Au(111) with molecular
      resolution.

PMID- 14695609
TI  - A better understanding of the self-structuration of bridged silsesquioxanes.

PMID- 14695610
TI  - Two unprecedented 3-connected three-dimensional networks of copper(I)
      triazolates: in situ formation of ligands by cycloaddition of nitriles and
      ammonia.

PMID- 14695611
TI  - Hexanuclear manganese(III) single-molecule magnets.

PMID- 14695612
TI  - Activation of C--Cl and C--H bonds by ligated S2(2-) ions: conversion of organic
      chlorides into organosulfur compounds in cis-[(IrCp*)(2)(micro-CH(2))(2)(micro
      S2R)](+).

PMID- 14695613
TI  - Highly enantioselective construction of a chiral tertiary carbon center by
      alkynylation of a cyclic N-acyl ketimine: an efficient preparation of HIV
      therapeutics.

PMID- 14695614
TI  - Hydrido(hydrosilylene)tungsten complexes with strong interactions between the
      silylene and hydrido ligands.

PMID- 14695615
TI  - Direct evidence for extremely facile 1,2- and 1,3-group migrations in an FeSi2
      system.

PMID- 14695616
TI  - Synthesis and biological evaluation of an indomethacin library reveals a new
      class of angiogenesis-related kinase inhibitors.

PMID- 14695617
TI  - Noble-metal nanotubes (Pt, Pd, Ag) from lyotropic mixed-surfactant liquid-crystal
      templates.

PMID- 14695618
TI  - Supramolecular construction of molecular ladders in the solid state.

PMID- 14695619
TI  - A titanosilicate that is structurally analogous to an MWW-type lamellar
      precursor.

PMID- 14695620
TI  - Three-level synthetic strategy towards mixed-valence and heterometallic [2 x 2]
      gridlike arrays.

PMID- 14695621
TI  - Self-assembly in a bipolar phosphocholine-water system: the formation of
      nanofibers and hydrogels.

PMID- 14695622
TI  - Ligand-supported homology modeling of g-protein-coupled receptor sites: models
      sufficient for successful virtual screening.

PMID- 14695623
TI  - Farnesyltransferase inhibitors inhibit the growth of malaria parasites in vitro
      and in vivo.

PMID- 14695625
TI  - Glycophorin C (Gerbich antigen blood group) and band 3 polymorphisms in two
      malaria holoendemic regions of Papua New Guinea.
AB  - The geographic overlap between the prevalence of erythrocyte polymorphisms and
      malaria endemicity is thought to be an example of natural selection on human
      populations. In Papua New Guinea (PNG), the Gerbich-negative phenotype is caused
      by an exon 3 deletion in the glycophorin C gene (GYPCDeltaex3) while
      heterozygosity for a 27-base pair deletion in the SLC4A1 gene (anion exchanger 1
      or erythrocyte membrane protein, band 3), SLC4A1Delta27, results in Southeast
      Asian ovalocytosis. Two geographically and ethnically distinct malaria endemic
      regions of PNG (the Wosera [East Sepik Province] and Liksul [Madang Province])
      were studied to illustrate the distribution of two prominent deletion
      polymorphisms (GYPCDeltaex3 and SLC4A1Delta27) and to determine if the genetic
      load associated with SLC4A1Delta27 would constrain independent assortment of
      GYPCDeltaex3 heterozygous and homozygous genotypes. The frequency of the
      GYPCDeltaex3 allele was higher in the Wosera (0.463) than Liksul (0.176) (chi(2);
      P < 0.0001). Conversely, the frequency of the SLC4A1Delta27 allele was higher in
      Liksul (0.0740) than the Wosera (0.0005) (chi(2); P < 0.0001). No individuals
      were homozygous for SLC4A1Delta27. In 355 Liksul residents, independent
      assortment of these two deletion polymorphisms resulted in 14 SLC4A1Delta27
      carriers heterozygous for GYPCDeltaex3 and one SLC4A1Delta27 carrier homozygous
      for GYPCDeltaex3 (Fisher's exact test; P = 0.8040). While homozygosity for
      SLC4A1Delta27 appears to be nonviable, the GYPCDeltaex3 allele is not lethal when
      combined with SLC4A1Delta27. Neither mutation was associated with altered
      susceptibility to asymptomatic Plasmodium falciparum or P. vivax infection. While
      these erythrocyte polymorphisms apparently have no effect on blood-stage malaria
      infection, their contribution to susceptibility to clinical malaria morbidity
      requires further study.

PMID- 14695626
TI  - Stem cell transplantation post invasive fungal infection is a feasible task.
AB  - Between March 1997 and January 2002, 18 consecutive patients (18-47 years) with
      hematological malignancies and previous proven invasive fungal infection
      underwent stem cell transplantation (SCT) (10 matched sibling allograft, 6
      autograft, and 2 haploidentical). All patients had full myeloablative
      conditioning. The fungal pathogens diagnosed were Aspergillus (14), Fusarium (2),
      Mucor (1), Exserohilum (1), and Candida (1), involving the lungs (15), sinuses
      (5), and liver (1). All patients were treated pre- and during transplant with
      systemic antifungal therapy. Eleven out of 18 (61%) patients survived the
      transplant. Only 1 of 5 patients who transplanted with an active fungal infection
      accompanied with active leukemia survived the transplant, compared with 10/13
      (84%) survivals in patients who had no clinical and radiological signs of
      infection or active leukemia (P < 0.025). None of the autografted patients has
      died, compared with 7/12 allografted patients, of whom 5 underwent transplant
      with active hematological/active fungal disease. In only 3 patients was the cause
      of death reactivation of previous fungal infection. Both active fungal infection
      and active leukemia place patients at a very high risk for procedure-related
      mortality. Pre-transplant therapy of fungal infection, aiming to achieve a
      clinically undetectable state of infection, followed by an antifungal treatment
      during transplant may allow the SCT with no fungal reactivation in selected
      patients.

PMID- 14695627
TI  - Accuracy of identification of patients with immune thrombocytopenic purpura
      through administrative records: a data validation study.
AB  - Administrative data are commonly used to estimate the prevalence of a disease,
      but the validity of the coding system needs to be evaluated before its use. We
      assessed the validity of the International Classification of Disease, 9(th)
      version, Clinical Modification (ICD-9-CM) code of 287.3 for identifying patients
      with immune thrombocytopenic purpura (ITP). Administrative data from inpatients
      and outpatients seen were retrieved if the patient or insurer was billed with one
      of three ICD-9-CM codes for thrombocytopenic disorders, 287.3, 287.4, and 287.5,
      as a primary or secondary diagnosis; or was physician-identified as having ITP.
      The electronic medical records for these patients were systematically reviewed to
      identify patients with ITP and with non-ITP diagnoses. Sensitivity, specificity,
      positive and negative predictive values, and kappa scores were calculated
      separately for inpatients and outpatients. Four-hundred eighteen records were
      reviewed. Among inpatients, the sensitivity of code 287.3 for indicating a
      diagnosis of ITP was 100% [95% confidence interval 94-100%]. The specificity was
      89% [95% confidence interval 84-94%]. The percent agreement was 92%, and the
      kappa statistic was 0.80. For outpatients, the sensitivity of the billing code
      287.3 was 84% [95% confidence interval 76-91%], a conservative estimate because
      of how the patients with other diagnoses were selected. The specificity for
      outpatients was 66% [95% confidence interval 56-76%]. ICD-9-CM code 287.3 in
      administrative billing data is likely to be sufficiently sensitive and specific,
      particularly when inpatient data are used, for the estimation of the prevalence
      of ITP.

PMID- 14695628
TI  - Morphologic diagnosis of thrombotic thrombocytopenic purpura.
AB  - The diagnosis of thrombotic thrombocytopenic purpura (TTP) rests on evidence of
      microangiopathic hemolytic anemia and thrombocytopenia in the absence of
      disseminated intravascular coagulation and other known causes of thrombotic
      microangiopathy. Highly specific diagnostic tools such as serum levels of
      ADAMTS13 are not routinely available for immediate clinical diagnosis. The
      presence of schistocytes on a blood smear is the morphologic hallmark of the
      disease, but no guidelines exist as to the number of schistocytes required to
      differentiate TTP from other thrombotic microangiopathies. We studied 6 patients
      with TTP and compared their schistocyte counts with those of 40 normal subjects,
      28 patients with chronic renal disease, 5 with preeclampsia, and 5 with normal
      functioning mechanical heart valves. The mean schistocyte count for the TTP
      patients was 8.35% versus 0.05% for normal subjects, 0.2% for renal patients,
      0.25% for preeclamptic patients, and 0.18% for patients with mechanical valves (P
      < 0.001). Schistocytes were found on 100% of blood films of TTP patients and
      ranged from 1.0% to 18.4% of red cells. Schistocytes are found on the smears of
      58% of normal individuals and on 80-100% of the other patient groups studied, but
      always comprise less than 0.5% of the red cell population. An initial schistocyte
      count of greater than 1% strongly suggests a diagnosis of TTP in the absence of
      other known causes of thrombotic microangiopathy.

PMID- 14695629
TI  - Mcl-1 and Bcl-2/Bax ratio are associated with treatment response but not with Rai
      stage in B-cell chronic lymphocytic leukemia.
AB  - Although both Bcl-2/Bax ratio and Mcl-1 have been identified to be of clinical
      relevance in B-cell chronic lymphocytic leukemia (CLL), there is controversy
      regarding their role; further, their relative importance is not well delineated.
      Expression of Bcl-2, Bax, the Bcl-2/Bax ratio, and Mcl-1 in 51 consecutive
      previously untreated CLL patients and 16 controls was determined by Western
      blotting. Only 37 patients were treated, all with chlorambucil and prednisone
      initially. Six patients achieved complete response (CR), 14 were non-responders
      (NR), and 17 had a partial response (PR), as defined by NCI criteria. There was
      considerable inter-patient variability in protein expression and overlap with
      healthy volunteers (P > 0.05). All patients with CR had low Mcl-1 levels compared
      to the PR + NR group (0.07 +/- 0.02 vs. 0.14 +/- 0.07, P = 0.043). Higher Mcl-1
      expression as determined by dichotomizing the data was associated with a failure
      to achieve CR (P = 0.021). The Bcl-2/Bax ratio was significantly associated with
      treatment response only when CR and PR were considered together (0.89 +/- 0.53
      [CR + PR] vs. 3.38 +/- 4.47 [NR], P = 0.0118). There was no association with Rai
      stage. Low Mcl-1 appears to be a requirement for CR, while low Bcl-2/Bax ratio is
      indicative of some response to conventional treatment.

PMID- 14695630
TI  - A non-immunological phospholipid-dependent coagulation inhibitor associated with
      IgGlambda-type multiple myeloma.
AB  - We investigated the rare case of a patient with IgGlambda multiple myeloma for
      whom both prothrombin time and APTT were significantly prolonged. The IgG
      inhibited coagulation reactions upstream from prothrombin when coagulation was
      initiated by mRVVT, but not by FXa, as indicated by a chromogenic substrate for
      FXa. The mPT and the mAPTT showed inhibition of FXa generation in both the
      intrinsic and extrinsic pathways. The IgG inhibited both protein C (indicated by
      APTT) and FX (indicated by RVV) but not amidolysis for either activated protein C
      or FXa. The addition of excess phospholipid significantly shortened the prolonged
      RVVT of the patient. It inhibited the coagulation reactions of normal plasma and
      was dependent on decreasing the PS concentration in the APTT reagent. It was
      suggested that the IgG showed lupus anticoagulant (LA)-like activity that
      inhibited phospholipid-dependent coagulation reactions in the intrinsic,
      extrinsic, and common pathways. However, the IgG did not bind cardiolipin
      beta2GPI complex, beta2GPI, or prothrombin in ELISA assays. The IgG did not bind
      to either PS or phospholipid complexes in the presence or absence of prothrombin,
      FX, or FXa. Interestingly, the IgG lost its LA like-activity when it was degraded
      to F(ab')2 and Fc fragments by pepsin. We suspected that the IgG might inhibit
      the interaction between coagulation factors and acid phospholipid non
      immunologically and that this process requires an intact IgG conformation,
      although the reaction mode is still not clear.

PMID- 14695631
TI  - Risk of bleeding complications with antiplatelet agents: meta-analysis of 338,191
      patients enrolled in 50 randomized controlled trials.
AB  - Antiplatelet therapy has been the focus of extensive clinical investigations over
      the last two decades. A variety of agents and regimens have been advanced for the
      prevention and treatment of vascular disease. Despite the proven life-saving
      clinical benefits of inhibiting platelets, this therapy is associated with an
      increased risk of bleeding. The objective of this study was to determine the risk
      of hemorrhage in the major classes of antiplatelet agents. Data from clinical
      trials published 1988-2002 in English were retrieved from MEDLINE, OVID, and
      CARDIOSOURCE. Only those studies in which patients had clinical follow-up for at
      least 1 month and in which a full description of hemorrhagic complications was
      reported were included. Information on sample size, study design, duration,
      agent, patient characteristics, and bleeding severity was independently and
      blindly reviewed. Data from 51 clinical trials with a total of 338,191 patients
      were analyzed. The antiplatelet agents were divided into 6 groups: aspirin (ASA)
      < 100 mg; ASA > or = 100 mg; dipyridamole, thienopyridines; intravenous and oral
      GP IIb/IIIa inhibitors. The variance estimate and confidence intervals were
      calculated for each treatment assignment. Low-dose aspirin and dipyridamole
      therapy were associated with the lowest risk of bleeding (3.6% and 6.7%,
      respectively). The highest rate of bleeding complications (44.6%) was associated
      with the GP IIa/IIIb inhibitors. Despite substantial differences in the reporting
      patterns of bleeding complications, low-dose ASA and dipyridamole therapy were
      associated with the lowest risk. Surprisingly, doses of ASA >/= 100 mg caused a
      relatively high hemorrhagic event rate, which was comparable to that of ADP
      receptor blockers. These findings should be considered when using combination
      antiplatelet and/or anticoagulant therapy with conventional doses of ASA.

PMID- 14695632
TI  - Transfusion-related acute lung injury (TRALI) following allogeneic stem cell
      transplant for acute myeloid leukemia.
AB  - Transfusion-related acute lung injury (TRALI) is a serious complication of
      transfusion characterized by dyspnea, hypoxemia, hypotension, fever, and
      bilateral pulmonary infiltrates. Although the frequency is estimated at 1/1,120
      to 1/5,000 transfusions, few cases have been reported after hematopoietic stem
      cell transplant. We report a case occurring in an allogeneic transplant recipient
      who developed acute respiratory distress and bilateral pulmonary infiltrates 2 hr
      after a platelet transfusion due to the presence of anti granulocyte antibody HNA
      3a in the product. As there is a wide differential diagnosis for pulmonary
      infiltrates developing post transplant, TRALI may be under-recognized and should
      be considered in this setting.

PMID- 14695633
TI  - Myocardial infarction in a patient with beta-thalassemia major: first report.
AB  - Thalassemia is the most common hereditary anemia throughout the world. Survival
      in its most severe long-term form, beta-thalassemia major, has significantly
      risen in the last decades. Cardiac morbidity-heart failure and dysrhythmias-is
      still the most common cause of mortality in these patients. We describe herein a
      case of myocardial infarction with normal coronary arteries in a 48-year-old
      patient with beta-thalassemia and no other recognized risk factors for coronary
      artery disease. Thromboembolic phenomena, a known situation in these patients,
      occur at a frequency of 4-5%. However, as far as we know, this is the first
      report in the literature of myocardial infarction in association with beta
      thalassemia. With the notable improvement in the life expectancy of thalassemia
      patients, ischemic heart disease may become an important complication encountered
      in these patients.

PMID- 14695634
TI  - Warfarin-associated multiple digital necrosis complicating heparin-induced
      thrombocytopenia and Raynaud's phenomenon after aortic valve replacement for
      adenocarcinoma-associated thrombotic endocarditis.
AB  - Necrosis of the digits is a rare complication of warfarin therapy of obscure
      pathogenesis. We report a 61-year-old woman with a 12-month history of Raynaud's
      phenomenon who developed multiple digital necrosis following aortic valve
      replacement with mechanical prosthesis for aortic insufficiency caused by
      nonbacterial thrombotic endocarditis. Exacerbation of Raynaud's phenomenon
      occurred during the postoperative period, with daily episodes of ischemia of the
      fingers and toes that improved with local warming. However, coincident with the
      occurrence of immune heparin-induced thrombocytopenia, and while undergoing
      routine warfarin anticoagulation because of the mechanical valve prosthesis, the
      patient abruptly developed progression of digital ischemia to multiple digital
      necrosis on postoperative day 8, at the time the international normalized ratio
      reached its peak value of 4.3. All limb pulses were readily palpable, and
      vascular imaging studies showed thrombosis only in the superficial femoral and
      popliteal veins of the right leg. Coagulation studies showed greatly elevated
      levels of thrombin-antithrombin complexes and prothrombin fragment F1.2 levels,
      consistent with uncontrolled thrombin generation. After vitamin K administration,
      no abnormalities of the protein C anticoagulant pathway were identified,
      consistent with previous studies of other patients with warfarin-induced necrosis
      complicating heparin-induced thrombocytopenia. Subsequently, the patient was
      shown to have metastatic breast adenocarcinoma, which explained the patient's
      initial presentation with nonbacterial thrombotic endocarditis. This patient case
      suggests that multiple digital gangrene can result from the interaction of
      various localizing and systemic factors, including compromised microvascular
      blood flow (Raynaud's phenomenon), increased thrombin generation (heparin-induced
      thrombocytopenia, adenocarcinoma), and warfarin-induced failure of the protein C
      natural anticoagulant pathway.

PMID- 14695636
TI  - Meta-analysis for trend estimation.
AB  - Grouped dose measures, heterogeneity and publication bias are three major
      problems for meta-analysis in trend estimation. In this paper, we propose a model
      that allows for arbitrarily aggregated dose levels, and show that the resulting
      estimates and standard errors can be quite different from those given by the
      usual assigned value method. Based on fitting a model to the funnel plot, we
      discuss a method for random-effects sensitivity analysis that deals with the
      problems of heterogeneity and publication bias. A meta-analysis of
      epidemiological studies on the effect of alcohol on the risk of breast cancer is
      used to illustrate the method. Our analysis suggests that the rate of increase in
      risk with alcohol consumption is substantially less than has been previously
      suggested.

PMID- 14695637
TI  - Small sample estimation of relative accuracy for binary screening tests.
AB  - Comparing the accuracy of two screening tests is ideally achieved by
      administering both tests as well as a gold standard test to all study subjects.
      In practice, a more ethical screen positive study design is often used, one that
      requires gold standard determination only for subjects that screen positive on
      either test under investigation. Although it is not possible to quantify the
      absolute accuracy of each test with such a design,the relative accuracy of the
      tests can be estimated. Since relative accuracy estimation has poor small sample
      properties, adjusted estimators based on adding constants to the observed data
      have been proposed. The adjusted estimators have the advantage that they yield
      point and variance estimates of relative accuracy in all settings. However, we
      show through both theory and numerical examples that adding constants to the data
      can be beneficial or detrimental to small sample performance. Furthermore, the
      performance of the adjusted estimator depends not only on the magnitude of the
      constant but also on parameters that cannot be estimated with data from a screen
      positive study, making selection of an optimal constant difficult in practice. We
      also examine the performance of the adjusted estimator using data from a study
      comparing the accuracy of two screening tests for cervical cancer.

PMID- 14695638
TI  - Estimating heterogeneous transmission with multiple infectives using MCMC
      methods.
AB  - We developed a general procedure for estimating the transmission probability
      adjusting for covariates when susceptibles are exposed to several infectives
      concurrently and taking correlation within transmission units into account. The
      procedure is motivated by a study estimating efficacy of pertussis vaccination
      based on the secondary attack rate in a rural sub-Saharan community (Niakhar,
      Senegal) and illustrated with simulations. The procedure is also appropriate to
      estimate the pairwise transmission probability in transmission studies of live
      vaccine virus in a collection of transmission units, such as day-care centres or
      retirement centres. Previously, analyses either excluded transmission units with
      multiple infectives or ignored co-infectives. Excluding transmission units with
      multiple infectives is statistically less efficient and ignoring co-infectives
      can lead to biased estimation. Modelling is carried out by regressing the latent
      pairwise transmission probability from each infective to a susceptible on
      covariates and specifying a transmission linkage function linking the latent
      pairwise transmission probability to the overall transmission probability.
      Parameters are estimated using Markov chain Monte Carlo methods.

PMID- 14695639
TI  - Regression models for relative survival.
AB  - Four approaches to estimating a regression model for relative survival using the
      method of maximum likelihood are described and compared. The underlying model is
      an additive hazards model where the total hazard is written as the sum of the
      known baseline hazard and the excess hazard associated with a diagnosis of
      cancer. The excess hazards are assumed to be constant within pre-specified bands
      of follow-up. The likelihood can be maximized directly or in the framework of
      generalized linear models. Minor differences exist due to, for example, the way
      the data are presented (individual, aggregated or grouped), and in some
      assumptions (e.g. distributional assumptions). The four approaches are applied to
      two real data sets and produce very similar estimates even when the assumption of
      proportional excess hazards is violated. The choice of approach to use in
      practice can, therefore, be guided by ease of use and availability of software.
      We recommend using a generalized linear model with a Poisson error structure
      based on collapsed data using exact survival times. The model can be estimated in
      any software package that estimates GLMs with user-defined link functions
      (including SAS, Stata, S-plus, and R) and utilizes the theory of generalized
      linear models for assessing goodness-of-fit and studying regression diagnostics.

PMID- 14695640
TI  - Effects and non-effects of paired identical observations in comparing proportions
      with binary matched-pairs data.
AB  - Binary matched-pairs data occur commonly in longitudinal studies, such as in
      cross-over experiments. Many analyses for comparing the matched probabilities of
      a particular outcome do not utilize pairs having the same outcome for each
      observation. An example is McNemar's test. Some methodologists find this to be
      counterintuitive. We review this issue in the context of subject-specific and
      population-averaged models for binary data, with various link functions. For
      standard models and inferential methods, pairs with identical outcomes may affect
      the estimated size of the effect and its standard error, but they have
      negligible, if any, effect on significance. We also discuss extension of this
      result to matched sets.

PMID- 14695641
TI  - Bagging survival trees.
AB  - Predicted survival probability functions of censored event free survival are
      improved by bagging survival trees. We suggest a new method to aggregate survival
      trees in order to obtain better predictions for breast cancer and lymphoma
      patients. A set of survival trees based on B bootstrap samples is computed. We
      define the aggregated Kaplan-Meier curve of a new observation by the Kaplan-Meier
      curve of all observations identified by the B leaves containing the new
      observation. The integrated Brier score is used for the evaluation of predictive
      models. We analyse data of a large trial on node positive breast cancer patients
      conducted by the German Breast Cancer Study Group and a smaller 'pilot' study on
      diffuse large B-cell lymphoma, where prognostic factors are derived from
      microarray expression values. In addition, simulation experiments underline the
      predictive power of our proposal.

PMID- 14695642
TI  - Improved estimates of floating absolute risk.
AB  - Floating absolute risks are an alternative way of presenting relative risk
      estimates for polychotomous risk factors. Instead of choosing one level of the
      risk factor as a reference category, each level is assigned a 'floated' variance
      which describes the uncertainty in risk without reference to another level. In
      this paper, a method for estimating the floated variances is presented that
      improves on the previously proposed 'heuristic' method. The estimates may be
      calculated iteratively with a simple algorithm. A benchmark for validating the
      floated variance estimates is also proposed and an interpretation of floating
      confidence intervals is given.

PMID- 14695643
TI  - Analysing Italian voluntary abortion data using a Bayesian approach to the time
      series decomposition.
AB  - After the approval of the law on voluntary abortion in Italy, the Italian health
      care system started to practice voluntary abortion before the third month of
      pregnancy. Since 1980, the Italian Institute of Statistics (ISTAT) has collected
      data on the abortion frequency per month and per administrative local areas.
      Although a preliminary analysis of the data showed that, after an initial
      increase, the number of abortions progressively lowered over years, there is no
      insight on the existence of periodicity in the time series and on the local
      effects related to the regional habits and social environments. The aim of our
      study is therefore to extract local trends and periodicity from the data
      collected by ISTAT, by combining a 'structural model' of the time series and
      Bayesian statistics. This paper describes both the adopted stochastic model and
      its Bayesian estimation through a Markov chain Monte Carlo approach on the
      Italian abortion data. Abortion data are analysed both at national level and in
      each of the 95 Italian local areas. At the national level this analysis allows
      extraction of a trend component that clearly shows that the voluntary abortion
      trend has decreased constantly since June-July 1983 until the end of the study.
      The periodic component shows an astonishing regularity too, suggesting that the
      Italian people have a seasonal preference for voluntary abortion. In particular,
      abortions are concentrated in the central part of the year (April-August).
      Finally, at the local level this analysis allows us to find
      similarities/differences between different areas in trends and/or in seasonal
      preferences.

PMID- 14695644
TI  - Spectrum bias: a quantitative and graphical analysis of the variability of
      medical diagnostic test performance.
AB  - The performance of a medical diagnostic test may vary in a subgroup of patients
      according to the severity and clinical presentation of the disease. This
      phenomenon is often referred to as the spectrum effect. There is currently no
      technique to determine in which situations this spectrum effect may lead to a
      spectrum bias, that is, a distortion of the posterior probability which can
      potentially affect the clinical decision. We show that spectrum bias, on either a
      positive or a negative test result, can be expressed as the subgroup-specific
      likelihood ratio (LR) divided by the LR in the overall population of patients.
      This assessment of spectrum bias is independent of the pretest probability. We
      present here the test statistic and its variance and also propose a mode of
      graphically visualizing the presence of spectrum bias. We applied it to 15
      examples from the literature, of which three are discussed in detail. In two
      examples, there was spectrum bias: (1) diagnosis of urinary tract infection in
      subgroups of low or high risk patients when using the dipstick test, and (2)
      diagnosis of left ventricular hypertrophy using electrocardiography in subjects
      with different body mass index. In a third example, there was no spectrum bias
      for the diagnosis of coronary heart disease in subgroups of patients defined by
      age, sex or comorbidities when using exercise electrocardiography. As sensitivity
      and specificity usually vary in opposite directions from one subgroup to the
      other, the ratio of LRs tends to remain constant, resulting in no or little
      spectrum bias. We conclude that spectrum effect is more common than spectrum bias
      and that clinical decisions are affected only under certain conditions.

PMID- 14695645
TI  - A multistage model for maternal morbidity during antenatal, delivery and
      postpartum periods.
AB  - There is acute dearth of information regarding factors affecting complications
      during different stages of childbearing in Bangladesh. This study employs a
      multistage model that involves transitions at different stages to complications.
      The proposed model appears to display more meaningful explanation concerning the
      impact of different factors on the incidence of complications taking into account
      types of transitions. Two alternative models are also presented in this paper in
      order to demonstrate possible simplifications of the proposed model. This study
      uses data from a prospective survey on Maternal Morbidity in Bangladesh. The
      survey was conducted during the period 11 1992-12 1993. A total of 1020 pregnant
      women were followed during pregnancy, delivery and 90 days after delivery. This
      study reveals some very important findings regarding the potential impact of
      antenatal visits, economic status, whether the index pregnancy was desired or not
      and number of pregnancies prior to the index pregnancy. It is observed that
      slightly more than 50 per cent of the women suffer from at least one of the major
      complications (haemorrhage, excessive vomiting, oedema and fits/convulsion)
      during pregnancy. It is noteworthy that if a woman suffers from one or more of
      the major complications during pregnancy, then it is more likely that she will
      suffer from complications during delivery. This study reveals that the women who
      suffer from one or more of the major complications during pregnancy are expected
      to have a substantially higher risk of suffering from complications during
      postpartum period, irrespective of no complications or complications during
      delivery. Generally speaking, higher economic status can reduce the complications
      at the postpartum stage, although women belonging to higher economic status may
      suffer from complications during pregnancy and delivery at a higher rate. It is
      surprising that antenatal visit is positively associated with incidence of
      complications during pregnancy and delivery, but antenatal visit reduces
      complications at the postpartum stage.

PMID- 14695647
TI  - Free amino acids mimic the anabolic but not the proliferative effect of albumin
      in OK proximal tubular cells.
AB  - When plasma proteins leak from circulation into the renal tubular lumen in the
      proteinuric renal diseases, nephrotoxicity of filtered albumin (and/or molecules
      bound to it) may be important in the subsequent development of tubulo
      interstitial damage which contributes to the progression of the disease. When
      cultured opossum kidney (OK) proximal tubular cells were exposed to bovine serum
      albumin for 3 days in vitro, increased cell division ([3H]-thymidine
      incorporation) and cellular hypertrophy (increased protein/DNA ratio) were
      observed. Both effects were halved if defatted albumin was used. A trivial
      explanation for the growth responses is that free fatty acids carried on the
      albumin, and amino acids generated by intracellular degradation of the albumin,
      are exerting a non-specific growth effect as metabolic fuels which are oxidized
      to generate ATP. However, the water-soluble free fatty acid octanoate (1 mmol l(
      1)) had no significant effect on protein/DNA ratio and a very variable
      stimulatory effect on [3H]-thymidine incorporation, whereas an essential amino
      acid mixture or 1 mmol/l(-1) l-Ala or l-Phe only increased the protein/DNA ratio.
      Furthermore no carnitine was added to the culture medium. This absence would have
      impaired mitochondrial transport (and hence oxidation) of long-chain free fatty
      acids derived from the albumin. l-Phe is also a poor substrate for mitochondrial
      oxidation in kidney. It is therefore concluded that the growth effects of albumin
      in OK proximal tubular cells are specific effects of the albumin protein and of
      the free fatty acids and amino acids derived from it, and not a non-specific
      effect on metabolic fuel supply.

PMID- 14695648
TI  - Liver denervation affects hepatocyte mitochondrial fatty acid transport capacity.
AB  - The effect of liver denervation on the activity of hepatic carnitine
      palmitoyltransferase (CPT) system, which catalyses the transfer of long-chain
      fatty acids into the mitochondria, was studied in rats. Noradrenaline content in
      phenol-denervated liver (D) was reduced by 87%. CPT I and II activities (measured
      by radioassay after detergent separation of the enzymes) were decreased (p <
      0.001) in D (2.6 +/- 0.1 and 0.68 +/- 0.2 nmol min(-1) mg(-1) protein,
      respectively) as compared with controls (4.7 +/- 0.3 and 2.5 +/- 0.2 nmol min(-1)
      mg(-1) protein, for CPT I and II, respectively). A less intense immunoreactive
      band for denervated liver CPT II was obtained after Western blotting.
      Concomitantly, long-chain fatty acid incorporation (p < 0.001), evaluated after
      administration of [14C]-oleate and total fat content (p < 0.001) were increased
      in D in relation to controls, while incorporation of exogenous [14C]-oleate into
      secreted VLDL, was decreased (p < 0.01). The effect of sympathetic denervation on
      CPT activity was different from that evoked by adrenodemedullation, which caused
      an augmentation of CPT activity (p < 0.01), when compared with the liver of
      intact rats. The effects of denervation and adrenodemedullation on the other
      parameters of lipid metabolism studied, were similar. The results strongly
      suggest a role of liver sympathetic innervation in the regulation of liver lipid
      metabolism.

PMID- 14695649
TI  - Lipid peroxidation, vitamins C, E and reduced glutathione levels in patients with
      pulmonary tuberculosis.
AB  - The present study examined the relationship between lipid peroxidation and
      vitamin C, vitamin E and reduced glutathione levels in plasma, erythrocytes and
      erythrocyte membranes of pulmonary tuberculosis patients and an equal number of
      age-and sex-matched healthy subjects. Enhanced plasma, erythrocytes and
      erythrocyte membrane lipid peroxidation with concomitant decline in vitamin C,
      vitamin E and reduced glutathione levels were found in pulmonary tuberculosis
      patients. The elevated lipid peroxidation and decreased vitamin C, vitamin E and
      reduced glutathione levels indicate the potential of oxidative damage to
      erythrocytes and erythrocyte membranes of pulmonary tuberculosis patients.

PMID- 14695650
TI  - NBD-cholesterol incorporation by rat macrophages and lymphocytes: a process
      dependent on the activation state of the cells.
AB  - The time-course of incorporation of NBD-cholesterol by macrophages (Ma) and
      lymphocytes (LY) obtained from untreated and thioglycollate-injected (thio) rats
      was investigated. NBD-cholesterol incorporation was also examined in Ma obtained
      from untreated rats and stimulated in vitro by lipopolysaccharide (LPS) and
      phorbol-myristate acetate (PMA). The same measurement was performed in LY from
      untreated rats stimulated by addition of LPS and concanavalin A (Con A) into the
      culture medium. Thio-treated Ma showed high fluorescence intensity after 1 h of
      incubation with NBD-cholesterol. Ma submitted concomitant to LPS and NBD
      cholesterol showed low fluorescence intensity, as well as Ma stimulated with PMA.
      Ma from untreated and LPS pre-treated rats showed a similar time-course of
      incorporation. LY from thio-treated rats showed lower incorporation of NBD
      cholesterol in comparison to LY from untreated rats. Incorporation was reduced
      when LPS was added concomitantly with NBD-cholesterol. On the other hand, LY pre
      treated with LPS for 48 h showed a very high incorporation of NBD-cholesterol.
      Con A treatment did not cause a significant effect on NBD-cholesterol
      incorporation. The findings presented herein led us to conclude that the uptake
      of NBD-cholesterol by Ma and LY is markedly affected by the activation state of
      the cells.

PMID- 14695651
TI  - Genotype and allele frequencies of polymorphic cytochromes P450 CYP1A2 and CYP2E1
      in Mexicans.
AB  - CYP1A2 and CYP2E1 are two of the main cytochrome P450 isoforms involved in the
      metabolism of commonly used drugs and xenobiotic compounds considered to be
      responsible for or possible participants in the development of several human
      diseases. Individual susceptibility to developing these pathologies relies, among
      other factors, on genetic polymorphism which depends on ethnic differences, as
      the frequency of mutant genotypes varies in different human populations. Thus the
      aim of this study was to investigate the frequency of CYP1A2 5'-flanking region
      and CYP2E1 Rsa I/Pst I polymorphisms in Mexicans by PCR-RFLP methods. The DNA of
      159 subjects was analysed and mutant allele frequencies of 30% for CYP2E1 Rsa
      I/Pst I sites and 43% for CYP1A2 5'-flanking region were found. These frequencies
      are higher than those previously reported for other human populations.

PMID- 14695652
TI  - Intracellular calcium release is required for caspase-3 and -9 activation.
AB  - Increase in intracellular Ca2+ [Ca2+]i regulates many biological functions
      including apoptosis, but the protein(s) linking [Ca2+]i and apoptosis are not
      completely understood. We have previously shown that IP3R-deficient cells are
      resistant to T-cell receptor (TCR)-induced apoptosis due to lack of Ca2+ release
      from endoplasmic reticulum (ER) and calcineurin activation. Here we show that
      caspase-9 and -3 are not activated in IP3R-deficient cells after TCR stimulation,
      consistent with the resistance of these cells to apoptosis. However, we also
      demonstrate that Bcl-2 expression in IP3R-deficient cells is comparable to
      control cells. Taken together, these results strongly suggest that IP3R-mediated
      Ca2+ release plays a critical role in regulating the activity of caspases-3 and 
      9 independent of Bcl-2.

PMID- 14695653
TI  - The mediating role of cPLA2 in IL-1 beta and IL-6 release in LPS-induced HeLa
      cells.
AB  - Studies were conducted to characterize a HeLa cell model by which the roles of
      the 85-kDa phospholipase A2 (cPLA2) in interleukin-1 beta (IL-1 beta) and
      interleukin-6 (IL-6) release could be evaluated. At first, untreated HeLa cells
      were compared with lipopolysaccharide (LPS)-treated HeLa cells. The latter
      resulted in cPLA2 overexpression and an increased trend of IL-1 beta and IL-6
      release. The indicated doses of 85-kDa cPLA2 antisense oligonucleotide directed
      against the initiation site were then used to block cPLA2 in LPS-induced HeLa
      cells. The process led to a dose-dependent decrease in cPLA2 protein with no
      noticeable change of cPLA2 mRNA. Compared with that of LPS added only, a
      reduction of IL-1 beta and IL-6 levels in the supernatants of transfected cells
      following the repression of cPLA2 was observed. These results suggested that 85
      kDa cPLA2 may mediate the signalling cascades by which IL-1 beta and IL-6 were
      released in LPS-induced HeLa cells.

PMID- 14695654
TI  - Toxic action of etoposide on mouse peritoneal macrophages and its modulation by
      interleukin 3.
AB  - In the present work, we have studied the toxic action of etoposide on mouse
      peritoneal macrophages. First, we have determined the induction of DNA
      fragmentation by this antitumour compound. To study the possible influence of
      interleukin 3 on the effects of etoposide on mouse macrophages, we studied
      intracellular protein phosphorylation induced by interleukin 3. After incubation
      of the cells in the presence of interleukin 3, increased phosphorylation levels
      of proteins of estimated molecular weights of around 29,000, 34,000, 50,000 and
      61,000 daltons were observed. We have also investigated a possible influence of
      interleukin 3 on DNA degradation induced by etoposide. The changes of Bax levels
      induced by etoposide that we have observed seemed to be modulated by this
      cytokine. From these results, a possible role of interleukin 3 can be suggested
      in the attenuation of some toxic effects produced by etoposide in mouse
      peritoneal macrophages. Thus, a therapeutic application of interleukin 3 on
      antitumour treatments in cells from the mononuclear phagocytic system might be
      proposed.

PMID- 14695655
TI  - Plasma lipid peroxidation and antioxidant levels in patients with rheumatoid
      arthritis.
AB  - In recent years, a great number of studies have investigated the possible role of
      reactive oxygen species in the aetiology and pathogenesis of rheumatoid arthritis
      (RA). The aim of this study was to investigate plasma concentrations of vitamin
      E, beta-carotene, activities of glutathione peroxidase (GSH-Px) and catalase,
      levels of lipid peroxidation (MDA) and reduced glutathione (GSH) in 36 patients
      with rheumatoid arthritis (RA) and 22 healthy age-matched controls. The plasma
      activity of GSH-Px and catalase (p < 0.001), levels of GSH (p < 0.01),
      concentration of beta-carotene (p < 0.05) and vitamin E (p < 0.001), haemoglobin
      and hematocrit (p < 0.05) were significantly lower in patients with RA than in
      controls. The MDA levels (p < 0.01), C reactive protein, rheumatoid factor, anti
      streptolysin-o values (p < 0.001), platelet count (p < 0.05) and erythrocyte
      sedimentation rate (p < 0.001) were higher in the patient group than in the
      control group. These results provide some evidence for a potential role of
      increased lipid peroxidation and decreased enzymic and non-enzymic antioxidants
      in RA by its inflammatory character. These results suggested that oxidant stress
      plays a very important role in the pathogenesis of RA.

PMID- 14695656
TI  - Effects of additional vitamin E and selenium supply on antioxidative defence
      mechanisms in the kidney of rats treated with high doses of glucocorticoid.
AB  - The aim of this work was to determine the effects of dietary vitamin E and
      selenium (Se) on lipid peroxidation as thiobarbituric acid reactive substances
      (TBARS) and on the antioxidative defence mechanisms in the kidney of rats treated
      with high-doses of prednisolone. Two hundred and fifty adult male Wistar rats
      were randomly divided into five groups. The rats were fed a normal diet, but
      groups 3, 4, and 5 received a daily supplement in their drinking water of 20 mg
      vitamin E, 0.3 mg Se, and a combination of vitamin E and Se, respectively, for 30
      days. For 3 days subsequently, the control group (group 1) was treated with a
      placebo, and the remaining four groups were injected intramuscularly with 100 mg
      kg(-1) body weight (bw) prednisolone. After the last administration of
      prednisolone, 10 rats from each group were killed at 4, 8, 12, 24, and 48 h and
      the activities of glutathione peroxidase (GSH-Px) and catalase (CAT) enzymes, and
      the levels of glutathione (GSH) and TBARS in their kidneys were measured. GSH-Px
      and CAT enzyme activities and GSH levels in the prednisolone treatment group
      (group 2) began to decrease gradually at 4 h, falling respectively to 48 and 65%
      of the control levels by 24 h, and recovering to the control levels at 48 h. In
      contrast, prednisolone administration caused an increase in TBARS in the kidneys,
      reaching up to twice the levels of the control group at 24 h. However,
      supplementation with vitamin E and Se had a preventive effect on the elevation of
      kidney TBARS and improved the diminished activities of the antioxidative enzymes
      and the levels of GSH. Therefore, the present study demonstrates the
      effectiveness of vitamin E and Se in reducing kidney damage in glucocorticoid
      treated rats and suggests that reductions in increased TBARS due to prednisolone
      may be an important factor in the action of vitamin E and Se.

PMID- 14695657
TI  - Predictors of sustained response to therapy resumption after treatment
      interruption in HIV-infected patients failing antiretroviral therapy.
AB  - In order to evaluate whether a sustained virologic response to therapy resumption
      after treatment interruption can be achieved in the setting of virologic failure,
      we reviewed retrospectively the data relating to 56 human immunodeficiency virus
      (HIV)-infected subjects selected from 3,145 patient charts. At the time of
      treatment interruption (study entry), the median (interquartile range) CD4+
      counts and HIV-RNA levels were respectively 247 (127-502) x 10(6) cells/L and
      4.24 (3.68-5.02) log(10) copies/ml, and the patients had been exposed to eight (5
      9) antiretroviral drugs. After treatment interruption, the patients received at
      least three drugs depending on their treatment history. Forty-eight weeks after
      the resumption of therapy, 19 of the 56 patients (34%) had HIV-RNA levels of <400
      copies/ml and, in comparison with study entry, the difference in the median
      increase in CD4+ counts between the virologic responders and non-responders (83
      vs. 8.5 x 10(6) cells/L) was statistically significant (P = 0.02). Multivariate
      analysis showed that higher peak HIV-RNA levels before treatment interruption
      were independently predictive of virologic failure, whereas a longer treatment
      interruption period independently correlated with a virologic response. Four
      patients with CD4+ counts of <200 x 10(6) cells/L at study entry developed HIV
      related clinical events. A sustained virologic response to therapy resumption
      after treatment interruption can be achieved in the setting of virologic failure.
      An evaluation of clinical history may help to identify the patients who are more
      likely to respond.

PMID- 14695658
TI  - The effect of highly active antiretroviral therapy for HIV on the anti-HCV
      specific humoral immune response.
AB  - The effect of highly active antiretroviral therapy (HAART) on HCV replication is
      controversial, with some studies reporting no effect and others increases,
      reductions and even clearances of HCV RNA after treatment. In this study, the
      effect of HAART was investigated on the titre of anti-HCV specific antibodies and
      on the relationship between these antibodies and HCV RNA level in a cohort of 24
      patients with inherited bleeding disorders. A significant inverse correlation
      between antibodies to both total HCV proteins and HCV RNA (R = -0.42, P = 0.05)
      and between antibodies to HCV envelope glycoproteins and HCV RNA (R = -0.54, P =
      0.01) was observed pre-HAART. The relationship disappeared or was obscured after
      therapy (R = 0.24, P = 0.30 and R = 0.16, P = 0.50, respectively). Thus, we show
      that HAART affects the HCV specific humoral immune responses without affecting
      the HCV RNA level.

PMID- 14695659
TI  - Hepatitis A vaccine: indirect evidence of immune memory 12 years after the
      primary course.
AB  - Vaccine-induced hepatitis A antibodies persist up to 10 years in adults, with
      mathematical models estimating further persistence up to 20-25 years. Thirty-one
      adults received booster inoculations 12 years after their initial vaccination
      (Havrix 720 El.U at months 0, 1, 6). At the time of booster inoculation, all
      still had detectable antibodies. All but one subject met pre-defined criteria for
      anamnestic response 14 days after the booster, and all subjects did so after 30
      days. The subjects' geometric mean titre (GMT) increased rapidly from 242 IU/L at
      baseline to 3,832 IU/L at day 14 and 5,282 IU/L at day 30. This study shows a
      substantial immune response to re-exposure to hepatitis A antigen after 12 years,
      which occurs rapidly to ensure protection within the average incubation period of
      hepatitis A virus.

PMID- 14695660
TI  - Seroprevalence of hepatitis A virus antibodies in Turkish and Moroccan children
      in Rotterdam.
AB  - Seasonal fluctuations in hepatitis A have been observed in the Netherlands
      related to Turkish and Moroccan children after visiting their home countries.
      This study determined the prevalence and associated factors of hepatitis A virus
      (HAV) antibodies in Turkish and Moroccan children in Rotterdam. A random sample
      was taken of children in Rotterdam, aged 5-16 years, of Turkish and Moroccan
      origin, together with a random sample of native Dutch children aged 5-7 and 14-16
      years. Blood was collected by finger prick on filter paper. IgG and IgM anti-HAV
      was detected by an enzyme-linked immunoassay (EIA). The 319 Turkish, 329
      Moroccan, and 248 native Dutch children participated in the study. In Turkish
      children, IgG anti-HAV increased from 2.2% to 22.2% over the age groups. In
      Moroccan children, IgG anti-HAV increased from 10.2% to 57.7%. In native Dutch
      children, 0.8% had IgG anti-HAV in the youngest and 3.1% in the oldest age group.
      The percentage IgG-positive also having IgM anti-HAV was 21% in Turkish, and 41%
      in Moroccan children. No IgG-positive native Dutch children had IgM anti-HAV. The
      prevalence of IgG anti-HAV was associated with increased age, being Moroccan,
      longer stay in the country of origin before migrating to the Netherlands, and
      known contact to HAV. The majority of Turkish and Moroccan children aged 4-16
      years in Rotterdam are not protected against HAV, but do have a high risk of
      becoming infected while visiting their native country. Active vaccination against
      HAV of these children is indicated, with as primary aim their own protection.
      Prevention of HAV-transmission in the general community should be seen as a
      secondary benefit. In addition, possible Dutch contacts of nonvaccinated Turkish
      and Moroccan children, such as day care workers and teachers, should also be
      vaccinated against HAV.

PMID- 14695661
TI  - Hepatitis B virus DNA in liver, serum, and peripheral blood mononuclear cells
      after the clearance of serum hepatitis B virus surface antigen.
AB  - The integration of hepatitis B virus (HBV) DNA in the liver of chronic HBV
      carriers has been documented extensively. However, the status of the viral genome
      during acute infection has not been assessed conclusively. While HBV DNA
      sequences are detected often in serum, liver, and peripheral blood mononuclear
      cells (PBMCs) after the clearance of serum the hepatitis B virus surface antigen
      (HBsAg), the precise status of the viral genome, and in particular the possible
      persistence of integrated genomes in PBMCs, has not been established. A highly
      sensitive PCR-derived assay (Alu-PCR) was employed to re-examine liver and PBMC
      specimens obtained from patients with acute (n = 19) and chronic (n = 22)
      hepatitis in whom serum HBsAg was present (n = 12) (HBV-related chronic active
      hepatitis) or absent with anti-HCV (n = 10) (HCV-related chronic active
      hepatitis). Viral integration was demonstrated in 3 out of 19 liver specimens
      from patients with acute hepatitis and 12 out of 12 specimens from patients with
      chronic hepatitis. Viral integration was also observed in 4 out of 7 PBMC samples
      from HBV-related chronic active hepatitis patients and 2 out of 10 liver and PBMC
      samples from HCV-related chronic active hepatitis patients. In one liver specimen
      from an acute hepatitis patient, HBV DNA was found integrated in the intronic
      sequence of the tumour necrosis factor (TNF)-induced protein gene; viral
      integration into cellular sequences was also found in the PBMCs of four HBV
      related chronic active hepatitis and two HCV-related chronic active hepatitis.
      The results demonstrate the early integration of HBV genome during acute viral
      infections and the persistence of the viral genome in an integrated form in
      PBMCs.

PMID- 14695662
TI  - Intrahepatic CD8 T-lymphocytes and HBV core expression in relation to response to
      antiviral therapy for chronic hepatitis B patients.
AB  - Recognition of HBV-infected hepatocytes by CD8 T-lymphocytes is important for
      viral clearance. Expression of hepatitis B core antigen (HBcAg) in HBV-infected
      hepatocytes can trigger this antiviral T-cell response. The intrahepatic CD8 T
      lymphocytes and HBcAg expression were investigated in relation to response to
      antiviral therapy. Forty chronic HBeAg-positive patients treated with either
      lamivudine (n = 20) or interferon-alpha (n = 20) were investigated. Ten patients
      from each treatment group exhibited a response. Liver biopsies were carried out
      before and after therapy. CD8 T-lymphocytes and HBcAg expression were detected by
      immunohistochemistry. The number of pretreatment intrahepatic CD8 T-lymphocytes
      was significantly higher in responders (P = 0.008). In responders baseline
      nuclear HBcAg expression tended to be lower (P = 0.09). Cytoplasmic expression
      was not significantly different between responders and non-responders (P = 0.46).
      The number of CD8 T-lymphocytes correlated with cytoplasmic HBcAg (r(s) = 0.31; P
      = 0.04); CD8 T-lymphocytes were situated in clusters of hepatocytes with
      cytoplasmic HBcAg. Longitudinal analysis showed a significant reduction of CD8 T
      lymphocytes after treatment in responders (P < 0.001). Multivariate analysis
      revealed pretreatment CD8 T-lymphocytes and age as independent prognostic factors
      for response (n = 40). The number of pretreatment CD8 T-lymphocytes was the only
      independent prognostic indicator for response to interferon-alpha (P = 0.03); it
      was of borderline significance for lamivudine therapy (P = 0.06). It is concluded
      that the number of pretreatment intrahepatic CD8 T-lymphocytes is an important
      predictor of response to HBV therapy with either interferon-alpha or lamivudine.
      Response to therapy led to a significant reduction of intrahepatic CD8 T
      lymphocytes. Co-localisation of CD8 T-lymphocytes and HBcAg-positive hepatocytes
      suggests antiviral activity predominantly at the site of maximum HBV replication.

PMID- 14695663
TI  - Virological significance of low-level hepatitis B virus infection in patients
      with hepatitis C virus associated liver disease.
AB  - The clinical and virological significance of low-level viremia by hepatitis B
      virus (HBV) in hepatitis C virus (HCV)-infected patients remains unclear. HBV-DNA
      and HCV-RNA were, therefore, quantitatively analyzed in livers and sera from co
      infected patients. HBV-DNA and HCV-RNA were quantitated using real-time detection
      of polymerase chain reaction (RTD-PCR), based on Taq-Man chemistry, in 220 non
      HCV-infected healthy volunteers and 93 HCV-infected patients without detectable
      HBsAg. Serum HBV-DNA was detected in 4 (1.8%) of 220 non-HCV-infected healthy
      volunteers and 32 (34.4%) of 93 HCV-infected patients without detectable HBsAg.
      HCV-infected patients displayed higher frequency of HBV infection than healthy
      volunteers (P < 0.0001). Hepatocellular carcinoma (HCC) was more frequent among
      co-infected patients than among HCV mono-infected patients (P < 0.001). However,
      quantities of HBV-DNA in sera from co-infected patients were very low (8-19,000
      copies/ml). HBV-DNA was detected in liver tissue from co-infected patients at 2
      20 copies per 100 hepatocytes, accounting for 1/1,000 to 1/10,000 of HBsAg
      positive patients. In livers of patients with HCC and HCV or HBV mono-infection,
      the viruses existed predominantly in non-cancerous tissue, with levels 10- to
      1,000-fold and 1- to 100-fold higher than in cancerous tissue, respectively. In
      contrast, patients co-infected with HCV and HBV displayed decreased HBV levels in
      non-cancerous tissue, but no change in cancerous tissue. These results indicate
      that low-level HBV infection exists in HCV-infected patients. HCC was more common
      among HCV/HBV co-infected patients than among HCV mono-infected patients. HCV
      might initiate hepatocarcinogenesis, but does not necessarily determine
      progression to HCC.

PMID- 14695664
TI  - Increased prooxidant production and enhanced susceptibility to glutathione
      depletion in HepG2 cells co-expressing HCV core protein and CYP2E1.
AB  - Hepatitis C virus (HCV) and HCV core protein are hypothesized to induce hepatic
      oxidative stress and exacerbate injury caused by other toxins such as ethanol
      that induce the cytochrome P450 enzyme, CYP2E1. In the current study, the effects
      of HCV core protein [sequence genotype 1b, (nt 342-915)] on parameters indicative
      of oxidative stress were evaluated in HepG2 cells stably over expressing CYP2E1
      (E47), or vector controls (C34). Stable (>10 passages) expression of HCV core
      protein and CYP2E1 was confirmed in clonal cell lines at the level of mRNA and
      immunoreactive protein. Prooxidant production, as determined by cellular
      oxidation of dichlorodihydrofluorescin and dihydroethidium (HE), was increased by
      expression of HCV core protein in the presence or absence of CYP2E1. Depletion of
      glutathione (GSH) with buthionine sulfoximine (BSO) enhanced prooxidant
      production in both C34 and E47 cells. In addition, prooxidant production was
      greater in BSO-treated cells expressing HCV core protein, and this effect was
      further enhanced in cells expressing both HCV core and CYP2E1. The CYP2E1
      inhibitor, 4-methylpyrazole, could suppress increased prooxidant production in
      E47 cells. Finally, cells co-expressing both CYP2E1 and HCV core protein showed
      significantly decreased viability following GSH depletion. These studies show
      simultaneous expression of HCV core protein and CYP2E1 increases parameters
      indicative of oxidative stress as well as sensitization to cell injury induced by
      GSH depletion. These results support the hypothesis that enhanced injury in
      hepatocytes over expressing both HCV core protein and CYP2E1 is mediated by
      increases in oxidative stress.

PMID- 14695665
TI  - Presence of specific viruses in the middle ear fluids and respiratory secretions
      of young children with acute otitis media.
AB  - The purpose of the study was to investigate the presence of different viruses in
      middle ear fluids and nasopharyngeal aspirates in young children with acute
      otitis media. Two cohorts of children (N = 329 and 611) were followed from 2 to
      24 months of age in Finland in two prospective studies (Finnish Otitis Media
      Cohort Study and Finnish Otitis Media Vaccine Trial). During the study period,
      nasopharyngeal and middle ear fluid specimens for each acute otitis media event
      were examined for eight (Cohort Study) or ten (Vaccine Trial) common respiratory
      viruses; adenoviruses, influenza viruses A and B, parainfluenza viruses 1, 2, and
      3, respiratory syncytial virus (RSV), enteroviruses, parechoviruses, and
      rhinoviruses. Picornaviruses (rhinoviruses, enteroviruses, and parechoviruses)
      were determined by reverse transcription PCR while antigen detection was used for
      the other viruses. A virus was present in either nasopharyngeal or middle ear
      specimen in 54% of events in the first cohort and in 67% of events in the second.
      Rhinoviruses formed the most common virus group detected (41-32%), followed by
      enteroviruses (25%, sought in the second cohort only) and respiratory syncytial
      virus (RSV) (10%). All the other viruses represented jointly 8-10% of the events.
      In conclusion, using the methods described in this study, a specific virus
      infection was diagnosed in two thirds of all acute otitis media events in young
      children. Picornavirus RNA was detected in association with more than a half of
      all acute otitis media events. The use of PCR-based methods for the other
      respiratory viruses might have increased further the overall virus detection rate
      in acute otitis media.

PMID- 14695666
TI  - Quantitation of cytomegalovirus DNA in cerebrospinal fluid and serum specimens
      from AIDS patients using a novel highly sensitive nested competitive PCR and the
      cobas amplicor CMV monitor.
AB  - A novel nested quantitative-competitive polymerase chain reaction (nQC-PCR) assay
      was developed to quantify as few as ten copies per tube of human cytomegalovirus
      DNA with an overall dynamic range of 10-10(5) copies per tube. This nQC-PCR assay
      is based on co-amplification of a mimic DNA and it was evaluated with 26
      cerebrospinal fluid (CSF) specimens and 44 serum specimens from 70 CMV-infected
      AIDS patients, 35 of them were diagnosed of CMV retinitis. An excellent
      correlation was found between nQC-PCR assay and the commercially available Cobas
      Amplicor CMV Monitor trade mark (CACM) assay (R = 0.9999; P < 0.001; n = 42).
      Moreover, 13 serum samples with CMV viral loads undetectable with the CACM were
      successfully quantified by nQC-PCR. CMV viral load was significantly higher in
      patients with CMV retinitis (P = 0.003). The nQC-PCR assay described below is a
      very sensitive test for accurate quantitative detection of CMV DNA in different
      clinical specimens that avoids the need for high-cost instrumentation.

PMID- 14695667
TI  - Cytomegalovirus and adenovirus infections and diseases among 75 paediatric
      unrelated allogeneic bone marrow transplant recipients.
AB  - Viral infections remain a major complication of allogeneic bone marrow
      transplantation. A population of children who underwent unrelated allogeneic bone
      marrow transplantation in a single centre has been followed-up for viral
      infections and diseases. We describe the detection of cytomegalovirus (CMV) and
      adenovirus among 75 children transplanted between 1989 and 2000. CMV was detected
      among 22 patients (29%) and adenovirus among 19 patients (25%); they were
      associated with clinical diseases in 10 and 8 patients, respectively. Four
      patients had adenovirus and CMV coinfection. The obvious risk factor for CMV
      infection is seropositivity of the recipient prior to transplantation. Adenovirus
      is detected significantly more frequently when conditioning regimen includes anti
      thymocyte or anti-lymphocyte globulin. Diseases associated with adenovirus have
      been correlated with a significantly higher mortality rate, stressing the need
      for the implementation of a systematic virological survey for this virus and for
      the evaluation of therapeutic protocols including new molecules.

PMID- 14695668
TI  - Inhibition of coxsackie B3 virus induced myocarditis in mice by 2-(3,4
      dichlorophenoxy)-5-nitrobenzonitrile.
AB  - Myocarditis is a common cause of dilated cardiomyopathy, one of the most
      important single causes of heart transplantation. Coxsackie B viruses (CBV) are
      considered to be the principal etiological agents of viral myocarditis and direct
      virus-induced damage to the heart tissue has been suggested to be the main
      mechanism underlying myocarditis in the murine model [Horwitz et al. 2000 Nat Med
      6:693-697]. We demonstrate that 2-(3,4-dichloro-phenoxy)-5-nitrobenzonitrile
      (DNB), a compound that was earlier shown to exhibit broad-spectrum anti
      picornavirus activity is also markedly active against CBV replication in primary
      human myocard fibroblast. To challenge the hypothesis of [Horwitz et al. 2000 Nat
      Med 6:693-697] we assessed whether DNB is able to prevent the development of CBV
      induced myocarditis in a murine model. Subcutaneous (s.c.) administration of DNB
      at 250 mg/kg/day, at multiple injection sites (m.i.s.), for a period of seven
      consecutive days (starting at 1 day before infection) to 4-week old C3H-mice
      resulted in a (i) 62% reduction in the number of myocarditis foci as compared to
      the untreated control animals (p = 1.7 x 10(-10)) and (ii) a concomitant
      reduction in viral titers in the heart. These findings indicate that selective
      inhibition of the replication of CBV may have a beneficial effect on the
      development of viral myocarditis and confirms that direct viral induced damage is
      the main mechanism underlying CBV-induced myocarditis. Early diagnosis of virus
      induced myocarditis will likely be mandatory for an antiviral drug treatment
      regimen to achieve its greatest clinical benefit.

PMID- 14695669
TI  - Molecular characterization of coxsackievirus B5 isolates.
AB  - Coxsackie B viruses of serotype 5 are associated frequently with sporadic cases
      of neurological diseases, epidemics of meningitis, and chronic diseases such as
      cardiomyopathy and diabetes. In this article, 15 strains of Coxsackievirus B5
      isolated from patients with neurological disorders and healthy people were
      investigated by partial sequencing in the 5' half of the VP1 region and compared
      to other published sequences of Coxsackievirus B5, in the same genomic region.
      All Coxsackievirus B5 sequences showed less than 25% nucleotide difference
      between each other and a minimum of 27.8% of divergence with prototype sequences
      from other Coxsackievirus B serotypes. Within the Coxsackievirus B5 group of
      sequences, four clusters were individualized and may correspond to four
      genotypes: one genotype with large geographical distribution, containing most
      recent strains that have circulated from 1984 to 2000, another genotype
      represented by the prototype Faulkner strain, isolated in the early 1950s, and
      two intermediate genotypes, comprising strains isolated from 1970 to 1999 and
      closely related to swine vesicular disease virus. This study confirms the ability
      of partial sequencing in VP1 to determine serotype and to genetically
      characterize Coxsackievirus B5 field isolates. It gives a first approach on the
      molecular epidemiology of these viruses, which have a particular importance in
      human health.

PMID- 14695670
TI  - Influence of antigenic drift on the intensity of influenza outbreaks: upper
      respiratory tract infections of military conscripts in Finland.
AB  - A total of 102,600 upper respiratory infections (URI) were recorded among young
      military conscripts in the Finnish Defence Forces during the study period from
      October 1991 to March 1994. This period covered three outbreaks caused by H3N2
      subtype influenza A virus and one outbreak of influenza B. During the 1991/92
      outbreak caused by A/Beijing/353/89-like virus, the calculated influenza A
      incidence was 2,206/10,000 men. During the 1992/93 outbreak when influenza B was
      the predominant virus, a new drift variant of influenza A that belonged to the
      lineage of A/Beijing/32/92-like and A/Shangdong/9/93-like viruses circulated but
      the incidence of influenza A was not more than 1,044/10,000. A higher incidence,
      2,810/10,000, was recorded during the 1993/94 outbreak, when the circulating
      virus was similar to the 1992/93 virus antigenically and with regard to
      haemagglutinin and neuraminidase (NA) gene sequences. Crossreactive
      haemagglutination-inhibition antibodies induced in 1991/92 probably were
      sufficient to restrict the epidemic activity in 1992/93 but no longer in 1993/94.
      Furthermore, during the 1991/92 outbreak, some of the A/Beijing/353/89-like
      viruses already had shared the NA sequence markers characteristic of the viruses
      in 1992/93 and 1993/94, which may also have strengthened protection in 1992/93.

PMID- 14695671
TI  - Genotyping of the JC virus in urine samples of healthy Korean individuals.
AB  - A human polyomavirus, JC virus (JCV) is ubiquitous in humans and infects children
      asymptomatically. It persists in renal tissue and is excreted progeny in urine.
      DNAs from urine samples of 100 healthy Korean individuals were screened for the
      presence of JCV by polymerase chain reaction (PCR). Twenty of the samples were
      positive for JCV. JCV DNA was found in one individual (4%) in the 1-19-year
      group, two individuals (9%) in the 20-39-year group, ten individuals (38%) in the
      40-59-year group, seven individuals (28%) in the over 60-year group. The
      prevalence of JC viral DNA was the highest in the 40-59-year-old Korean
      population. To investigate genotypes of JCV in Korea, the genotypes were
      determined by DNA sequence analysis of the regulatory region (333 bp) and the VT
      intergenic region (656 bp) of DNA from the 20 JCV isolates. We have identified
      three distinctive JCV strains in the regulatory region and ten distinctive JCV
      strains in the VT-intergenic region of DNA from the 20 isolates. Based on
      restriction fragment length polymorphism (RFLP) analysis and phylogenetic
      analysis of the VT-intergenic region of JCV, two distinct subtypes, CY and type
      2A (MY), were found to be prevalent in this Korean population. CY and type 2A of
      JCV were identified in 13 individuals (65%) and four individuals (20%),
      respectively. Interestingly, type 1, which was distributed mostly in Europe, was
      found in 3 (15%) isolates from healthy Korean individuals.

PMID- 14695672
TI  - Measles virus protein-specific IgM, IgA, and IgG subclass responses during the
      acute and convalescent phase of infection.
AB  - The availability of new generation serological assays allowed re-evaluation of
      the antibody response to measles virus. IgM, IgA, total IgG, and IgG subclass
      responses were studied to the three major immunogenic measles virus proteins: the
      fusion protein (F), haemagglutinin (H), and nucleoprotein (N). Plasma samples
      were obtained from clinically diagnosed measles cases (n = 146) in Khartoum
      (Sudan) within a week after onset of the rash. Convalescent phase samples were
      collected from 32 of 117 laboratory-confirmed measles cases at different time
      points after onset of rash. Glycoprotein-specific IgM, IgG, and IgA antibody
      levels correlated well to the N-specific response. For IgG and IgA, responses to
      F were higher than to H. IgA antibody levels were undetectable in about one third
      of the laboratory-confirmed cases during the acute phase, but positive in all
      patients tested 1-4 weeks after infection. IgM levels declined rapidly and were
      lost 3-6 months after infection. IgA levels declined slowly during the first year
      but did not return to background levels during the subsequent 2 years. IgG
      avidity maturation was detected during a 3-6 month period after infection. The
      predominant IgG subclasses during the acute phase were IgG(1) and IgG(3). The
      latter was lost in the convalescent phase, while the IgG(4) isotype showed a
      slight rise afterwards. Interestingly, acute phase IgG(3) and IgA responses were
      associated, and were only detected in samples with high IgG. This study provides
      a comprehensive perspective on the antibody response to wild-type measles virus
      infection.

PMID- 14695673
TI  - Evidence of human metapneumovirus in children in Argentina.
AB  - Human metapneumovirus (hMPV) is a virus, which was first associated with acute
      lower respiratory infection in children but is detected currently in all age
      groups. Clinical symptoms are similar to those described for respiratory
      syncytial virus (RSV) infections, ranging from mild respiratory illness to severe
      bronchiolitis and pneumonia in children. To date, no cases of hMPV have been
      reported in Argentina. In this study, 440 respiratory samples obtained during the
      period 1998-2002 from children under 5 years old with acute respiratory infection
      were evaluated. Routine detection for RSV, adenovirus, influenza, and
      parainfluenza was undertaken by immunofluorescent assay. Of the samples negative
      for these viruses, only 100 were available. All these samples were tested for
      hMPV by RT-PCR using primers for the L gene. Eleven out of 100 (11%) respiratory
      samples were positive for hMPV by RT-PCR. A higher frequency of detection was
      observed in spring. hMPV was detected in all the years studied, except in 2001.
      Ten out of 11 children positive for hMPV were hospitalized. Median age was 5
      months. Of seven patients, five (71%) required oxygen supplementation. The most
      frequent diagnosis was bronchiolitis (86%), sometimes accompanied by
      conjunctivitis and otitis media. The present study showed that hMPV was
      associated with acute lower respiratory infections in children in Buenos Aires,
      Argentina. This evidence strongly suggests that hMPV is a common pathogen with a
      wide geographical distribution, which should be included in the routine diagnosis
      of respiratory viruses in young children.

PMID- 14695674
TI  - Comparison of the seroprevalence of human metapneumovirus and human respiratory
      syncytial virus.
AB  - Human metapneumovirus (hMPV) is a virus that induces human respiratory syncytial
      virus (hRSV)-like illnesses, ranging from upper respiratory tract infection to
      severe bronchiolitis and pneumonia. The 100 serum samples from children aged 1
      month to 5 years were tested for the presence of hMPV and hRSV antibodies using
      an indirect immunofluorescence assay and a neutralizing-antibody assay,
      respectively. The seroprevalence of hMPV was significantly lower than that of
      hRSV in children over 4-months-old (43% vs. 60%, P < 0.025), and the difference
      was particularly notable between the ages of 4 months and 1 year (11% vs. 48%, P
      = 0.006). The results suggest that primary infection with hMPV occurs somewhat
      later than that with hRSV.

PMID- 14695675
TI  - Surveillance of norovirus infection in a study of sporadic childhood
      gastroenteritis in South West England and South Wales, during one winter season
      (1999-2000).
AB  - Reverse transcriptase polymerase chain reaction (RT-PCR), electron microscopy
      (EM) and a genotype II specific antigen capture enzyme immunoassay (EIA),
      (Lordsdale strain) were used to establish the prevalence of Norwalk-like viruses
      (NLV) among sporadic cases of childhood gastroenteritis in South West England
      over a winter season. Samples of 3,172 stools from cases of gastroenteritis in
      children aged under 7 years sent to the Bristol Public Health Laboratory over the
      1999/2000 winter 'season' were tested prospectively by EM, EIA and RT-PCR. The
      results from sporadic cases were compared with 1,360 samples from 285 outbreaks
      of gastroenteritis which were sent to the laboratory over the same period. In
      total NLV was established as the causal agent in 326 cases (10.3%) of sporadic
      gastroenteritis by one or more of the tests (EM 30 (0.9%), EIA 132 (4.2%) and RT
      PCR 276 (8.7%)). The presence of other enteric viruses was established using EM
      and rotavirus EIA. Rotaviruses were the most common cause of viral
      gastroenteritis with 684 cases (21.6%). Other viruses detected included,
      adenovirus 124 cases (3.9%), astrovirus 97 cases (3.1%) and calicivirus in 7
      cases (0.2%). NLV was the second most common viral agent indicating a significant
      role in cases of sporadic childhood gastroenteritis.

PMID- 14695676
TI  - Detection and characterization of norovirus outbreaks in Germany: application of
      a one-tube RT-PCR using a fluorogenic real-time detection system.
AB  - Outbreaks of gastroenteritis caused by Norovirus are an increasing public health
      problem worldwide. The virus is transmitted by contaminated food and by person-to
      person. In Germany, a new health reporting system including Norovirus infections
      has been introduced in 2001. Norovirus outbreaks (73%) diagnosed in our lab
      occurred in the first half of the year. Phylogenetic analysis shows that 90%
      belonged to genogroup II (GGII) with the majority related to prototypes
      Lordsdale/93 and Tarragona/2001. To date, PCR is the most sensitive and specific
      method for the detection but several procedures are needed to evaluate the
      amplification product. To minimize the risk of product carryover, a fast and
      simple procedure with a minimal number of steps are required. A one-tube RT-PCR
      method is described using the real-time TaqMan-PCR system. Primer sets and probes
      for both genogroup I (GGI) and genogroup II (GGII) sequences were developed. The
      specificity and sensitivity of this method was evaluated on 70 Norovirus positive
      stool samples of 70 outbreaks in Germany and 34 European samples by comparing the
      detection rate to those of an in-house RT-nested PCR. Overall, 93% of the PCR
      positive samples have been detected by the TaqMan-PCR including isolates of four
      different GGI and seven different GGII genotypes. Using plasmid standards for
      quantitation, virus loads between 10(2) and 10(10) genomic equivalents/ml stool
      suspension were found. The advantages of the one-step RT/TaqMan-PCR system for
      detection and quantitation of Norovirus are the high throughput of clinical
      samples and a decrease of the risk of contamination.

PMID- 14695677
TI  - Antigenic and genetic characterization of serotype G2 human rotavirus strains
      from South Africa from 1984 to 1998.
AB  - Within South Africa, cyclic peaks of serotype G2P[4] rotavirus infection have
      been observed and these strains were prevalent in some locations. To examine the
      cyclic phenomenon of serotype G2 rotaviruses, historical stool collections from
      South Africa spanning 15 years were screened for G2 strains. Subgroup (VP6)
      ELISA, polyacrylamide gel electrophoresis (PAGE), and P genotyping were performed
      on 43 G2 strains to investigate the associated DS-1 genogroup characteristics.
      Antigenic variation of the gene encoding the major neutralization glycoprotein
      (VP7) was also investigated using G2-specific monoclonal antibodies. In addition,
      the VP7 gene of 14 serotype G2 strains was sequenced to examine genetic
      variation. Serotype G2 strains from South Africa displayed a 10 year cyclic
      pattern with major epidemics occurring in 1987 and 1997. Serotype G2 strains were
      also found co-dominant with G(1) strains in 1984, 1990, and 1993. The G2 strains
      from the major epidemics appeared to have emerged from community strains in a
      manner similar to that suggested for G(1) strains The serotype G2 strains
      displayed subgroup I specificity and short electropherotypes characteristic of DS
      1 genogroup rotavirus strains but appeared to differ in the VP4 gene. Genetic
      analyses revealed three major serotype G2 lineages, i.e., strains isolated prior
      to 1987, strains isolated between 1988 and 1994, and strains isolated from 1995.
      The use of monoclonal antibodies and PCR primers designed against older G2
      strains has resulted in the failure to serotype G2 strains circulating currently.

PMID- 14695678
TI  - Prevalence of human T-cell leukemia virus types I and II in Switzerland.
AB  - The retroviruses human immunodeficiency virus (HIV)-1/2 and human T-cell leukemia
      virus (HTLV)-I/II share modes of transmission, suggesting that efforts to monitor
      the current HIV-1 epidemic in Switzerland should be complemented by assessment of
      HTLV-I/II prevalence. This study presents an updated evaluation of HTLV-I/II
      infection among groups within the Swiss population polarized towards either low
      or increased risk of infection. Archived serum and peripheral blood mononuclear
      cell (PBMC) samples were examined for evidence of HTLV-I/II infection by enzyme
      linked immunosorbant assay (ELISA), type-specific Western blot, type-specific
      polymerase chain reaction (PCR), DNA sequence analysis, and virus culture. Among
      blood donations obtained from low-risk Swiss donors, we report a complete lack of
      HTLV-II infection and the occurrence of HTLV-I infection limited to a prevalence
      of 0.079 per 100,000 (1/1,266,466). Among high-risk HIV-positive persons and HIV
      negative persons at increased risk of HIV-infection, we report a focus of HTLV-I
      and HTLV-II infection at prevalence rates of 62 per 100,000 (1/1,620) and 309 per
      100,000 (5/1,620), respectively. The finding of low HTLV-I/II prevalence among
      Swiss blood donors and containment of HTLV-I/II infection within known risk
      groups does not support initiation of HTLV-I/II screening for Swiss blood,
      tissue, and organ donations.

PMID- 14695679
TI  - Monitoring for potentially xenozoonotic viruses in New Zealand pigs.
AB  - Shortage of human donor organs for transplantation has prompted evaluation of
      animals as an alternative donor source. Pigs are the most acceptable candidate
      animals but issues of xenozoonozes remain. Despite careful monitoring of high
      health-status (HHS) pigs, there is still a risk that their tissues may carry
      infectious agents. Furthermore, pathogens which are significant in
      xenotransplantation are not necessarily those of veterinary importance. The
      detection of these potentially transmissible infectious agents may require the
      development and application of new surveillance technologies. We present data on
      monitoring for five potentially xenotic viruses in New Zealand pig herds, namely
      pig cytomegalovirus (PCMV), pig lymphotropic herpesvirus (PLHV),
      encephalomyocarditis virus (EMCV), pigcircovirus (PCV), and hepatitis E virus
      (HEV). These five viruses are either potentially oncogenic, establish persistent
      infection, or are known to be zoonotic. This study has expanded significantly the
      information on porcine viruses in New Zealand. Using this information, it is now
      possible to complete protocols for monitoring pig herds and tissues prior to
      their use in xenotransplantation. The study resulted in selection of a possible
      source herd for swine-to-human islet transplantation.

PMID- 14695683
TI  - Retrospect: 1903-1945.

PMID- 14695684
TI  - Ray Rappaport chronology: Twenty-five years of seminal papers on cytokinesis in
      the Journal of Experimental Zoology.

PMID- 14695685
TI  - Effect of gonadal steroids on progesterone receptor, estrogen receptor, and
      vitellogenin expression in male turtles (Chrysemys picta).
AB  - Hepatic vitellogenin (vtg) is a yolk precursor protein sequestered in follicular
      oocytes as nutrient supply for developing embryos in nonmammalian vertebrates. In
      prior research studies we have demonstrated that both progesterone (P) and
      testosterone (T) inhibit estrogen (E)-induced vitellogenesis in the male fresh
      water turtle (Chrysemys picta), and have suggested that these hormones may be
      involved in multihormonal regulation of vitellogenesis in the female turtle.
      However, the modes of action of progesterone and testosterone on estrogen-induced
      vitellogenesis are not known. We have proposed that progesterone inhibits
      vitellogenesis by modulation of progesterone receptor A (PRA) or B (PRB) isoforms
      and/or estrogen receptor (ER) gene transcription. In this study, we compare the
      vitellogenic responses of reproductively inactive male turtles to estradiol
      17beta in the presence of exogenous testosterone or progesterone. Northern blot
      analysis was used to monitor the changes in vtg mRNA, ER mRNA, and PR mRNA
      expression; Western blotting to determine changes in PR isoform expression and a
      homologous ELISA for measurement of plasma vtg. Progesterone and testosterone
      reduced estrogen-induced vtg mRNA expression, but plasma vtg was not
      significantly reduced by these steroids. PRA and PRB were transcribed even though
      ER mRNA could not be detected, suggesting constitutive PR expression. However, in
      the presence of estradiol 17beta, both PR isoforms and mRNA transcripts were
      increased as a correlate of ER mRNA transcription, suggesting both
      transcriptional and translational effects; these effects were inhibited by
      testosterone and progesterone treatments. Since ER mRNA was sharply reduced by
      both testosterone and progesterone, and estradiol 17 beta increased PR mRNA
      transcription and translation, it is likely that the action of progesterone in
      reducing vtg mRNA is indirect via down regulation of ER mRNA, thus ER. This study
      provides further information on the role of progesterone and testosterone in the
      regulation of hepatic vitellogenesis, suggesting regulation of vitellogenesis
      mainly via modulation of hepatic ER mRNA.

PMID- 14695686
TI  - Comparative analysis of methods for determining bite force in the spiny dogfish
      Squalus acanthias.
AB  - Many studies have identified relationships between the forces generated by the
      cranial musculature during feeding and cranial design. Particularly important to
      understanding the diversity of cranial form amongst vertebrates is knowledge of
      the generated magnitudes of bite force because of its use as a measure of
      ecological performance. In order to determine an accurate morphological proxy for
      bite force in elasmobranchs, theoretical force generation by the
      quadratomandibularis muscle of the spiny dogfish Squalus acanthias was modeled
      using a variety of morphological techniques, and lever-ratio analyses were used
      to determine resultant bite forces. These measures were compared to in vivo bite
      force measurements obtained with a pressure transducer during tetanic stimulation
      experiments of the quadratomandibularis. Although no differences were found
      between the theoretical and in vivo bite forces measured, modeling analyses
      indicate that the quadratomandibularis muscle should be divided into its
      constituent divisions and digital images of the cross-sections of these divisions
      should be used to estimate cross-sectional area when calculating theoretical
      force production. From all analyses the maximum bite force measured was 19.57 N.
      This relatively low magnitude of bite force is discussed with respect to the
      ecomorphology of the feeding mechanism of S. acanthias to demonstrate the
      interdependence of morphology, ecology, and behavior in organismal design.

PMID- 14695687
TI  - Active uptake and transport of protein by the intestinal epithelial cells in
      embryo of viviparous fish, Neoditrema ransonneti (Perciformes: Embiotocidae).
AB  - Neoditrema ransonneti is a matrotrophic viviparous fish. To clarify the site and
      process of protein uptake in the fetus of N. ransonneti, rabbit IgG and equine
      ferritin were administered into the ovarian cavity of pregnant females. Both
      proteins were absorbed by epithelial cells of hypertrophied intestine within 2h.
      Rabbit IgG appeared to be concentrated in large cytoplasmic vacuoles of which
      diameter sometimes reached more than 2 micro m. On the other hand, electron
      microscopy showed that ferritin was transported as middle-sized granules (smaller
      than 1 microm) and not accumulated in large vacuoles. The granules were
      transported through intra- and inter-cellular pathways and released into
      submucosal spaces. Furthermore, a number of fine granules of ferritin were seen
      in the lumen of intravillus capillaries. Western blotting showed that absorbed
      the rabbit IgG reached the circulating blood intact. These findings suggest that
      fetuses of N. ransonneti actively absorb maternally supplied proteins via
      enterocytes, and exploit them not only as nutrients but also as physiologically
      active molecules.

PMID- 14695688
TI  - Ion transport in the intestine of Gobius niger in both isotonic and hypotonic
      conditions.
AB  - Ion transport in the intestine of Gobius niger, a euryhaline teleost, was studied
      in both isotonic and hypotonic conditions. Isolated tissues, mounted in Ussing
      chambers and bilaterally perfused with isotonic Ringer solution, developed a
      serosa negative transepithelial voltage and a short circuit current indicating a
      net negative current in absorptive direction. Bilateral removal of Cl- and Na+
      from the bathing solutions as well as the luminal removal of K+in the presence of
      Ba2+(10(-3) M) almost abolished both Vt and Isc. Similar results were obtained by
      adding bumetanide (10(-5)M) to the luminal bath while other inhibitors of Cl-
      transport mechanisms were ineffective. These observations suggest that salt
      absorption begins with a coupled entry of Na+, Cl-, and K+ across the apical
      membrane; a Ba2+inhibitable K+ conductance, demonstrated also by micropuncture
      experiments, recycles the ion into the lumen. Salt entry into the cell is driven
      by the operation of the basolateral Na+/K(+)-ATPase since serosal ouabain (10(
      4)M) completely abolished both Vt and Isc; this pump also completes the Na(+)
      absorption. The inhibitory effect of both serosal bumetanide (10(-4)M) and SITS
      (5 x 10(-4)M) suggests that Cl- would leave the cell via the KCl cotransport, the
      Cl/HCO3- antiport and/or conductive pathways. Bilateral exposure of tissues to
      hypotonic media produced a reduction of both the transepithelial voltage and the
      short circuit current probably due to the activation of homeostatic ionic fluxes
      involved in cell volume regulation. The results of experiments with both isolated
      enterocytes and intestine exposed to hypotonic solution suggested that the
      recovery of cell volume, after the initial cell swelling, involves a parallel
      opening of K+ and Cl- channels to facilitate net solute and water effluxes from
      the cell. J. Exp. Zool. 301A:49-62, 2004.

PMID- 14695689
TI  - Modulation of gill Na+,K+-ATPase activity by ammonium ions: Putative coupling of
      nitrogen excretion and ion uptake in the freshwater shrimp Macrobrachium
      olfersii.
AB  - The effect of NH4+ ions on (Na+,K+)-ATPase hydrolytic activity was examined in a
      gill microsomal fraction from M. olfersii. In the absence of NH4+ ions, K+ ions
      stimulated ATP hydrolysis, exhibiting cooperative kinetics (nH=0.8), to a maximal
      specific activity of V=556.1+/-22.2 nmol.min(-1).mg(-1) with K(0.5)=2.4+/-0.1
      mmol.L(-1). No further stimulation by K+ ions was observed in the presence of 50
      mmol.L(-1) NH4+ ions. ATP hydrolysis was also stimulated by NH4+ ions obeying
      Michaelian kinetics to a maximal specific activity of V=744.8+/-22.3 nmol.min(
      1).mg(-1) and KM=8.4+/-0.2 mmol.L(-1). In the presence of 10 mmol.L(-1) K+ ions,
      ATP hydrolysis was synergistically stimulated by NH4+ ions to V=689.8+/-13.8
      nmol.min(-1).mg(-1) and K(0.5)=6.6+/-0.1 mmol.L(-1), suggesting that NH4+ ions
      bind to different sites than K+ ions. PNPP hydrolysis was also stimulated
      cooperatively by K+ or NH4+ ions to maximal values of V= 235.5+/-11.8 nmol.min(
      1).mg(-1) and V=234.8+/-7.0 nmol.min(-1).mg(-1), respectively. In contrast to ATP
      hydrolysis, K(+)-phosphatase activity was not synergistically stimulated by NH4+
      and K+ ions. These data suggest that at high NH4+ ion concentrations, the (Na+,
      K+)-ATPase exposes a new site; the subsequent binding of NH4+ ions stimulates ATP
      hydrolysis to rates higher than those for K+ ions alone. This is the first
      demonstration that (Na+, K+)-ATPase activity in a freshwater shrimp gill is
      modulated by ammonium ions, independently of K+ ions, an effect that may
      constitute a fine-tuning mechanism of physiological relevance to osmoregulatory
      and excretory processes in palaemonid shrimps.

PMID- 14695690
TI  - Intracellular pH regulation in isolated hepatopancreas cells from the Roman snail
      (Helix pomatia).
AB  - The mechanisms of intracellular pH (pHi) regulation were studied in isolated
      hepatopancreas cells from the Roman snail, Helix pomatia. The relationship
      between intracellular and extracellular pH indicated that pHi is actively
      regulated in these cells. At least three pHi-regulatory ion transporters were
      found to be present in these cells and to be responsible for the maintenance of
      pHi: an amiloride-sensitive Na+/H+ exchanger, a 4-acetamido-4'
      isothiocyanostilbene-2,2'disulfonic acid (SITS)-sensitive, presumably Na(+)
      dependent, Cl-/HCO3-exchanger, and a bafilomycin-sensitive H(+)-pump. Inhibition
      of one of these transporters alone did not affect steady state pHi, whereas
      incubation with amiloride and SITS in combination resulted in a significant
      intracellular acidification. Following the induction of intracellular acidosis by
      addition of the weak acid Na+propionate, the Na+/H+ exchanger was immediately
      activated leading to a rapid recovery of pHi towards the baseline level. Both the
      SITS-sensitive mechanism and the H(+)-pump responded more slowly, but were of
      similar importance for pHi recovery. Measurement of pHi recovery from
      acidification in the three discernible types of hepatopancreas cells with a video
      fluorescence image system revealed slightly differing response patterns, the
      physiological significance of which remains to be determined.

PMID- 14695691
TI  - Time-course changes in the expression of Na, K-ATPase and the morphometry of
      mitochondrion-rich cells in gills of euryhaline tilapia (Oreochromis mossambicus)
      during freshwater acclimation.
AB  - Changes in expression of Na, K-ATPase (NKA) and morphometry of mitochondrion-rich
      (MR) cells in gills of tilapia were investigated on a 96-hr time course following
      transfer from seawater (SW) to fresh water (FW). A transient decline in plasma
      osmolality and Na+, Cl- concentrations occurred from 3 hrs onward. Gills
      responded to FW transfer by decreasing NKA activity as early as 3 hrs from
      transfer. This response was followed by a significant decrease in the NKA isoform
      alpha1-mRNA abundance, which was detected by real-time PCR at 6 hrs post
      transfer. Next, a decrease of alpha1-protein amounts were observed from 6 hrs
      until 24 hrs post transfer. Additionally, during the time course of FW transfer,
      modifications in number and size of subtypes of gill MR cells were observed
      although no significant difference was found in densities of all subtypes of MR
      cells. These modifications were found as early as 3 hrs, evident at 6 hrs
      (exhibition of 3 subtypes of MR cells), and mostly completed by 24 hrs post
      transfer. Such rapid responses (in 3 hrs) as concurrent changes in branchial NKA
      expression and modifications of MR cell subtypes are thought to improve the
      osmoregulatory capacity of tilapia in acclimation from hypertonic SW to hypotonic
      FW.

PMID- 14695692
TI  - Diet quality differentially affects breeding effort of Mastomys coucha and M.
      natalensis: Implications for rodent pests.
AB  - In this study we compare the reproductive ability of Mastomys natalensis, an
      agricultural rodent pest and that of the closely related species M. coucha, which
      has not been ascribed as a pest. We suggest that the ability of M. natalensis to
      plague, as well as dominate, resource-limited habitats, may in part be related to
      its differential breeding response to variation in diet quality. Thus, we
      examined the reproductive response of M. coucha and M. natalensis mothers to
      variation in dietary protein intake. Our results demonstrated that typical levels
      of reproduction extended over a narrower range of dietary protein content for M.
      coucha than M. natalensis females. Only M. natalensis females bred on 6% protein
      diets, while on 20% protein diets the reproductive output of M. coucha was lower
      than on diets containing 10- and 15% protein. M. natalensis responded to low
      protein diets by reducing litter size and litter mass but not individual pup
      mass. Thus, providing diet quality improves before parturition, conception under
      sub-optimal conditions may not compromise individual pup growth. Furthermore, the
      ability of M. natalensis to breed under conditions of low diet quality may
      advance their breeding season compared to species that cannot breed until diet
      quality improves, allowing M. natalensis to produce additional litters through
      the season, while more daughters could reproduce during the season of their
      birth, both factors that are known to contribute to the plaguing tendency of M.
      natalensis.

PMID- 14695693
TI  - New antiviral therapies for hepatitis C.

PMID- 14695694
TI  - [Recent changes of organism and treatment in pyogenic liver abscess].
AB  - BACKGROUND/AIMS: With the advance of antibiotics and the development of newer
      imaging techniques, marked changes in etiology, diagnosis, treatment and
      prognosis of liver abscess have been reported. METHODS: We reviewed the clinical
      data related to 94 patients with pyogenic liver abscess. RESULTS: Of the 94
      patients in the study group, the male to female ratio was 1.4:1 and the peak
      incidence of liver abscess was in the 7th decade. About three quarters (74.5%) of
      the abscesses were of unknown origin. The predominant location was in the right
      lobe (70.3%). Single lesion was found in 80 patients and multiple lesions in 14
      patients. Pathogens were identified in 67 patients, of which Klebsiella
      pneumoniae (65.7%) and E. coli (16.4%) were the most common. The modalities of
      treatment were percutaneous drainage with antibiotics (73.4%), percutaneous
      aspiration with antibiotics (16.0%), or antibiotics alone (8.5%). The case
      fatality rate, mainly from associated underlying diseases, was 9 cases (9.6%).
      Associated diseases were diabetes mellitus (14.9%) and malignancy (10.6%).
      CONCLUSIONS: Our study revealed that the most common organism was Klebsiella
      pneumoniae and percutaneous needle aspiration and/or catheter drainage were safe
      and effective treatment modalities for pyogenic liver abscess. Prognosis was
      determined by the underlying condition.

PMID- 14695695
TI  - [Serum ALT and HBV DNA levels in patients with HBeAg-negative chronic hepatitis
      B].
AB  - BACKGROUND/AIMS: HBeAg-negative chronic hepatitis B (CHB) has a poor long-term
      prognosis. Since no precise clinically relevant HBV thresholds are known in HBeAg
      negative CHB, the decision to treat is difficult. The aim of this study was to
      evaluate the levels of serum HBV DNA and transaminase and to investigate the
      correlation of these values in patients with HBeAg-negative CHB. METHODS: The
      study analyzed the sera from 82 patients with HBeAg-negative CHB, 61 men and 21
      women. The mean age was 45 years. The patients were divided into two groups
      according to serum ALT levels: the patients with lower ALT level (n=52, UNL < ALT
      < 2 X UNL) and higher level (n=30, ALT >/= 2 X UNL). The level of serum HBV DNA
      was determined by the Cobas Amplicor HBV Monitor(TM) (Roche). RESULTS: The median
      serum HBV DNA level was 2.7 X 10(5) copies/mL in patients with HBeAg-negative
      CHB. The median serum HBV DNA level of patients with a higher ALT level (1.0 X
      10(6) copies/mL) was significantly higher than that of patients with a lower ALT
      level (5.6 X 10(4) copies/mL)(p<0.001). The serum ALT level was correlated with
      serum HBV DNA levels in patients with HBeAg-negative CHB (r=0.416, p<0.001). The
      serum level of HBV DNA in patients with cirrhosis (median 2.0 X 10(5) copies/mL)
      did not differ from patients without cirrhosis (median 4.7 X 10(5) copies/mL).
      CONCLUSIONS: The level of serum HBV DNA was higher in patients with higher serum
      ALT level than it was in patients with lower serum ALT, and it was closely
      correlated with serum ALT levels in HBeAg-negative CHB.

PMID- 14695696
TI  - [Predictive factors and clinical outcome of viral breakthrough during lamivudine
      treatment for chronic hepatitis B infection].
AB  - BACKGROUND/AIMS: Long-term treatment with lamivudine causes breakthrough, but the
      clinical course after lamivudine breakthrough is not well known. The aims of this
      study were to evaluate the clinical course in lamivudine after breakthrough, and
      to identify predictive factors of breakthrough. METHODS: 124 patients with
      chronic hepatitis B infection, who represented viral breakthrough during
      lamivudine therapy, were included. The mean duration of lamivudine therapy and
      additional lamivudine therapy after breakthrough was 30.5 months and 12.5 months,
      respectively. RESULTS: The cumulative breakthrough rates at 12, 18, 24 and 36
      months were 8, 24, 36 and 52%, respectively. After viral breakthrough, only 4
      patients maintained normal ALT levels. 120 patients showed ALT elevation. The
      number of patients with ALT levels greater than 5 times, and greater than 10
      times, the upper normal limit were 67 (56%) and 29 (24%), respectively. While
      still on lamivudine therapy after breakthrough, 98 patients presented ALT
      elevation. Only 22 had normalized ALT levels. Hepatic decompensation developed in
      2 patients. HBeAg seroconversion after breakthrough occurred in 10 patients. The
      changing pattern of quantitative HBeAg levels during lamivudine therapy was the
      only predictive factor associated with viral breakthrough. The mean time of
      turning points in decrescendo-crescendo patterns of HBeAg levels during
      lamivudine therapy was earlier than viral breakthrough (9 months vs. 17 months).
      CONCLUSIONS: These results suggested that deterioration of hepatic function can
      usually be observed after breakthrough. The serial monitoring of serum
      quantitative HBeAg levels may allow an early recognition of viral breakthrough.

PMID- 14695697
TI  - [Hepatitis B surface antigen and antibody positive rates of children and
      adolescents in Jeju].
AB  - BACKGROUND/AIMS: Korea has been an endemic area of Hepatitis B infection.
      Recently, the Hepatitis B carrier population has been significantly decreasing
      because of Hepatitis B vaccination. The aim of this study was to analyse the
      Hepatitis B surface antigen (HBsAg) and the Hepatitis B surface antibody (anti
      HBs) positive rates of children and adolescents in Jeju. METHODS: From January
      2000 to August 2002, seropositivity of HBsAg and anti-HBs were evaluated by
      enzyme immunoassay (EIA) in 1,653 pediatric patients. From April 2002 to August
      2002, seropositivity of HBsAg and anti-HBs were evaluated by reversed passive
      hemagglutination (RPHA) in 2,532 students. From July 1994 to February 2003,
      seropositivity of HBsAg was evaluated by EIA in 1,013 pregnant women. RESULTS:
      The positive rates of HBsAg and anti-HBs of children and adolescents in Jeju were
      2.1% and 70.9%, respectively. The positive rates of HBsAg of pregnant women in
      Jeju was 4.7% and that of HBeAg in HBsAg positive pregnant women was 38.1%. In
      children born after 1995, as age increased, HBsAg seropositivity increased
      significantly and anti-HBs seropositivity decreased significantly. There was no
      significant difference in testing HBsAg positivity between the RPHA and the EIA
      tests, but testing anti-HBs positivity by EIA was significantly higher than by
      RPHA. CONCLUSIONS: To reduce HBsAg positive rate, regular testing for anti-HBs by
      EIA may be indicated until at least 15 years after the primary vaccination
      schedule, and booster vaccination may be indicated in subjects whose anti-HBs
      titer was under 10 mIU/mL. 29.1% of children and adolescents in Jeju, therefore,
      may need to be revaccinated.

PMID- 14695698
TI  - [The clinical usefulness of balloon occluded retrograde transvenous obliteration
      in gastric variceal bleeding].
AB  - BACKGROUND/AIMS: Gastric variceal bleeding is difficult to treat endoscopically
      because the hemodynamics of the gastric varix are different from that of the
      esophageal varix. Transjugular intrahepatic portosystemic shunt (TIPS), which has
      been used widely, does not always result in the regression of gastric varix and
      it may aggravate the hepatic encephalopathy. Balloon occluded retrograde
      transvenous obliteration (BRTO) was introduced as a new procedure for gastric
      variceal bleeding with minimal invasiveness. The purpose of this study was to
      evaluate the therapeutic effects and complications on follow-up of BRTO as a new
      treatment option for gastric variceal bleeding. METHODS: Patients with gastric
      variceal bleeding, who were treated with BRTO form September, 2001 to April,
      2003, were included in the study. After the definite confirmation of the shunts
      with abdominal CT, the sclerosing agent, 5% ethanolamine oleate, was injected
      into the gastric varix during occlusion through gastrorenal shunts. The procedure
      was deemed a technical success when the clotting of the sclerosing agent was
      observed without leakage, and a clinical success when bleeding stopped and the
      varix decreased in size or was eradicated during the follow-up period (6-23
      months, mean: 17.7). RESULTS: Technical success was achieved in 12 of 13 patients
      (92%) with gastric variceal bleeding. There were no significant side effects. In
      the one case of failure, the bleeding was controlled with TIPS. Eleven of the 12
      patients who had technical success were shown to be clinically successful. The
      follow-up endoscopic exam showed some aggravation of pre-existing esophageal
      varices in four patients and a new development of esophageal varices in two
      patients. Endoscopic variceal ligation was done on one patient in whom esophageal
      variceal bleeding was present during the follow-up period. CONCLUSIONS: BRTO was
      proven to be a feasible, safe and less invasive procedure than TIPS and found to
      be an effective treatment of a gastric variceal bleeding. Considering the
      possible aggravation of pre-existing esophageal varices or the new development of
      esophageal varices, regular endoscopic examinations might be needed during the
      follow-up period.

PMID- 14695699
TI  - [The significance of urine sodium measurement after furosemide administration in
      diuretics-unresponsive patients with liver cirrhosis].
AB  - BACKGROUND/AIMS: The diagnosis of refractory ascites means a poor prognosis for
      patients with liver cirrhosis. The definition of refractory ascites has already
      been established, but using the dosage of diuretics that correlates with the
      definition of refractory ascites in an out-patient department will lower the
      compliance of the patient, as well as causing serious complications, such as
      hepatic encephalopathy and hyponatremia, as the dosage of diuretics is increased.
      Due to this fact, it is very difficult to apply this definition of refractory
      ascites to patients in a domestic out-patient department. In this study, in
      situations where there are difficulties in applying the diuretics dosage
      according to definition of refractory ascites, we tried to find out whether
      measuring the value of urine sodium after the administration of intravenous
      furosemide can be the standard in early differentiation of the response to
      diuretics treatment. METHODS: We reviewed 16 cases of liver cirrhosis with
      ascites and classified them into two groups by the response to diuretics. The
      diuretics-responsive ascites group was 8 cases and the diuretics-unresponsive
      ascites group consisted of 8 cases. After admission, we examined the patients'
      CBC, biochemical liver function test, spot urine sodium, and 24 hour creatinine
      clearance. After the beginning of the experiment, all diuretic therapy was
      stopped for 3 days. Daily we examined the patients' CBC, biochemical liver
      function test, and in the 3rd experiment day, we measured 24-hour urine volume
      and sodium. In the 4th experiment day, after sampling for ADH, plasma renin
      activity and plasma aldosterone level, we administrated the furosemide 80 mg I.V,
      and measured the amount of 8 hour urine volume and sodium. RESULTS: The plasma
      aldosterone level was significantly higher in the diuretics- unresponsive ascites
      group than in the diuretics-responsive ascites group. In the 4th experiment day,
      the amount of urine volume and sodium was very significantly lower in the
      diuretics-unresponsive ascites group than in the diuretics-responsive ascites
      group (1297.5 +/-80.9 vs 2003.7 +/-114.6 ml, p<0.005, 77.3 +/-8.2 vs 211.8 +/
      12.6 mEq, p<0.001). CONCLUSIONS: In out-patient departments, the measurement of
      urine sodium 8 hours after administrating 80 mg of intravenous furosemide, will
      help in differentiating ascites patients with lower treatment response to
      diuretics.

PMID- 14695700
TI  - [A case of toxic hepatitis induced by habitual glue sniffing].
AB  - The link between toxic hepatitis and exposure to organic solvents is relatively
      well-documented, but there are no specific laboratory or histologic findings
      diagnostic of chemical-induced hepatitis. Clinical history, therefore, is very
      important in making a diagnosis. A history of glue sniffing is sometimes
      overlooked and glue sniffing has not received much attention as a cause of
      hepatitis. Toluene, a main organic solvent in glue, is known to cause
      disturbances in various organs such as the heart, nervous system, liver and
      kidneys. We present a case of hepatitis in an individual who has sniffed glue for
      euphoria for 3 years. There is an increasing tendency towards glue sniffing among
      young adolescents today, so toxicity caused by exposure to organic solvents
      should be considered as one possible cause of hepatitis in young adolescents.

PMID- 14695701
TI  - [Usefulness of endoscopic mucosal resection for curative treatment of early
      gastric cancer].
AB  - BACKGROUND/AIMS: Endoscopic mucosal resection (EMR) has been widely accepted as a
      curative treatment of early gastric cancer (EGC). The aim of this study was to
      determine the usefulness and limitations of EMR for treatment of EGC by analyzing
      our own experience. METHODS: We retrospectively evaluated 51 EGC lesions (45
      mucosal and 6 submucosal cancers) from 49 patients who had undergone EMR between
      Oct. 1997 and Aug. 2002 at Inha Universtiy Hospital. RESULTS: Among 45 lesions of
      mucosal cancer, enbloc resection was performed in 13 lesions and piecemeal
      resection in 32 lesions. Complete resection rates of enbloc and piecemeal
      resection were 84.6% and 43.8%, respectively (p=0.012). Complete resection rate
      of the lesions smaller than 1 cm in size was 71.4%, 1 to 2 cm in size 52%, and
      greazter than 2 cm in size 37.5%. Complete resection rates of well, moderately,
      and poorly differentiated EGC were 59.4%, 71.4%, and 16.7%, respectively
      (p=0.048). Thirty-three patients underwent a follow-up endoscopy at I month after
      EMR and two were found to have residual cancers. One patient who had a piecemeal
      EMR showed cerical and abdominal lymph node metastasis 10 months after EMR.
      CONCLUSIONS: In selected patients with EGC, EMR can be a curative treatment
      modality. However, complete resection rate is low in large sized and poorly
      differentiated EGCs and when piecemeal resection is performed.

PMID- 14695702
TI  - [Relationship between esophageal lesions observed by endoscopy and nasogastric
      intubation: a study of 185 cases of percutaneous endoscopic gastrostomy].
AB  - BACKGROUND/AIMS: Percutaneous endoscopic gastrostomy (PEG) is a method widely
      used for long-term enteral nutrition in dysphagia. Mostly, it is preceded by
      nasogastric intubation (NI) for short-term enteral nutrition; endoscopic findings
      associated with NI are encountered during PEG. The purpose of this study was to
      discuss such findings and to delineate a relationship between these findings,
      especially esophageal lesions and the duration of NI. METHODS: This study
      involved 185 individuals who had undergone PEG at Kyung Hee Medical Center from
      January 1999 to May 2002. The medical records were examined retrospectively.
      RESULTS: The dysfunction of the CNS comprised 98.4% of the causes of dysphagia.
      The duration of NI was 15.2 weeks on average, with median value of 8.7 weeks,
      indicating that PEG was performed relatively soon. Endoscopic findings revealed
      esophagitis in 63 cases, esophageal ulcers in 27 and active bleedings in another
      10. The incidence of esophageal lesions was shown to be higher in subjects with
      duration of NI under 12 weeks than in those with duration over 12 weeks
      (p=0.032). CONCLUSIONS: PEG was carried out in many cases during the early stages
      of dysphagia, and NI-associated esophageal lesions appeared to be more prevalent
      within 12 weeks of NI duration. These results may be of help in deciding the
      timing of PEG.

PMID- 14695704
TI  - [Sequence analyses of aberrant FHIT transcripts in gastric cancer cell lines].
AB  - BACKGROUND/AIMS: The fragile histidine triad (FHIT) gene located at chromosome
      3p14.2, is a candidate tumor suppressor gene often involved in various tumors.
      Homozygous deletions, lack or reduced expression of FHIT protein, and alteration
      of its transcription were frequently observed in several types of primary human
      cancers and cell lines. In the present study, we examined the expression profiles
      of aberrant FHIT transcripts to explore the role of FHIT gene in gastric
      carcinogenesis. METHODS: In 6 gastric cancer cell lines, nested reverse
      transcription-polymerase chain reaction (RT-PCR) and cDNA sequence analyses were
      performed to detect and characterize the aberrant FHIT transcripts. RESULTS: In
      addition to the wild-type FHIT transcript, small-sized transcripts with various
      numbers and lengths were observed in all of the cell lines examined. cDNA
      sequence analysis confirmed that different types of truncated transcripts
      included exonic deletions, insertions of intron 5 sequences between exons, and
      combinations of both. Most of these transcripts lacked exon 5 in which
      translation initiation codon is located. Aberrant transcripts with partial exonic
      deletions due to activation of cryptic splice sites were also observed in 5 cell
      lines. Additionally, multi-step splice patterns indicative of additional
      downstream processing, were observed in several cancer lines. CONCLUSIONS: These
      results suggest that the aberrant FHIT transcripts in gastric cancer cell lines
      results from faulty splicing, including exon skipping, selection of cryptic
      splice site, and additional downstream splice processing.

PMID- 14695703
TI  - Efficacy of triple therapy with rabeprazole for Helicobacter pylori infection in
      relation to CYP2C19 genotype.
AB  - BACKGROUND/AIMS: Genetic polymorphism of cytochrome P450 CYP2C19 influences the
      efficacy of proton pump inhibitor (PPI) in Helicobacter pylori (H. pylori)
      eradication therapy. We investigated the difference in the cure rates of H.
      pylori infection by triple (rabeprazole plus amoxacillin and clarithromycin)
      therapy in relation to CYP2C19 genotype status. METHODS: One hundred and sixteen
      H. pylori infected patients with gastric ulcer and duodenal ulcer completed the
      triple therapy with 10 mg of rabeprazole b.i.d., 1,000 mg amoxacillin b.i.d. and
      500 mg of clarithromycin b.i.d. for one week. The genotype of CYP2C19 was
      determined by a PCR-restriction fragment length polymorphism method. RESULTS:
      According to the univariate analysis, heterozygous extensive metabolizers (hetero
      EMs) and poor metabolizers (PMs) showed the highest (87.0%) and the lowest
      (80.0%) eradication rates, respectively. The difference in the therapeutic
      efficacy of rabeprazole among the different CYP2C19 genotypes was insignificant.
      With regard to gender, age and smoking history in relation to eradication rate, a
      statistical significance was noted only with age with odds ratio of 1.063 and p
      value of 0.0202. CONCLUSIONS: In the eradication therapy of H. pylori, no
      statistically significant difference in therapeutic efficacy of rabeprazole was
      found among different CYP2C19 genotypes.

PMID- 14695705
TI  - A gene expression in study human gastric adenocarcinoma using a cDNA microarray.
AB  - BACKGROUND/AIMS: cDNA microarray provides a powerful alternative with an
      unprecedented view scope in monitoring gene expression levels and leads to
      discoveries of regulatory pathways involved in complicated biological processes.
      Our aim was to explore the different gene expression patterns in early and
      advanced gastric cancer. METHODS: By using a cDNA microarray representing 4,608
      cDNA clusters, we studied the expression profiling in 10 paired gastric
      adenocarcinoma samples and the adjacent noncancerous gastric tissues. The
      alterations in gene expression levels were confirmed by Northern blot and reverse
      transcription (RT) PCR. RESULTS: Genes that were differently expressed in cancer
      and noncancerous tissues were identified. Forty-four and 92 (26 and 43 of them
      were known, respectively) genes or cDNA were up- and down-regulated,
      respectively, in more than 80% of gastric adenocarcinoma samples. The semi
      quantitative RT-PCR results were consistent with the microarray findings. To
      distinguish between early and advanced gastric cancers, we used a supervised
      learning classification approach. When we used 16 and 20 genes as predictors, the
      prediction was all yielded statistically significant. Moreover, when we used 9
      genes, we could predict with the highest accuracy. CONCLUSIONS: These results may
      provide not only a new molecular basis for understanding biological properties of
      gastric adenocarcinoma, but also useful resources for future development of
      therapeutic targets and diagnostic markers for gastric adenocarcinoma.

PMID- 14695706
TI  - [Distribution of hepatitis B virus genotypes according to the clinical outcomes
      in patients with chronic hepatitis B virus infection in Jeju island].
AB  - BACKGROUND/AIMS: The genotype of hepatitis B virus (HBV) has been suggested to
      correlate with the clinical outcome of HBV infection. We analyzed the
      distribution of HBV genotypes according to the clinical outcomes of HBV infection
      in Jeju island. METHODS: A total of 145 HBsAg-positive samples were enrolled. To
      identify specific patterns of HBV genotypes, we performed restriction fragment
      length polymorphism (RFLP). In the case that typical restriction pattern of RFLP
      was not determined, phylogenetic analysis was performed. RESULTS: RFLP analysis
      was possible in 65 patients. Clinical diagnoses of the 65 patients with chronic
      liver disease were as follows: HBeAg-positive healthy carrier (HBeAg(+), anti
      HBe, HBV DNA(+), transaminase normal; n=20); Inactive HBsAg carrier (n=12);
      chronic hepatitis B (n=14); liver cirrhosis (n=9); hepatocellular carcinoma
      (n=10). Sixty-two patients showed a typical restriction pattern by HinfI.
      However, 3 patients showed a unique restriction pattern by HinfI, which were not
      reported in the literature. When phylogenetic analysis was performed to classify
      the genotype of these 3 patients, they were also genotype C. However, all 65
      patients showed typical restriction patterns by Tsp509I, which were reported in
      genotype C. CONCLUSIONS: All chronic HBV infections are genotype C in Jeju island
      regardless of clinical outcomes.

PMID- 14695707
TI  - [Efficacy of percutaneous ethanol injection therapy in Korean with hepatocellular
      carcinoma].
AB  - BACKGROUND/AIMS: Percutaneous ethanol injection therapy (PEIT) is widely used for
      the treatment of hepatocellular carcinoma (HCC). However, its long-term
      therapeutic efficacy is not verified in Korea, one of hepatitis B virus (HBV)
      endemic areas. Thus, this study was to assess its efficacy and prognostic factors
      affecting tumor-free survival following PEIT in Korean HCC patients. METHODS:
      From 1997 to 1999, 100 consecutive patients who had 1 to 3 HCC nodules of maximum
      diameter less than 3 cm and underwent PEIT were enrolled. Therapeutic efficacy,
      overall and tumor-free survival rates were assessed during follow-up periods.
      RESULTS: In 83 patients, HCC nodules were completely ablated by PEIT. The
      cumulative 1, 2, and 3 year overall survival rates were 98%, 96%, and 88%,
      respectively. The cumulative 1, 2, and 3 year tumor-free survival rates were 73%,
      50%, and 37%, respectively. Larger tumors (>or= 2 cm) were associated with a
      higher local recurrence rate. CONCLUSIONS: These results demonstrate that PEIT is
      therapeutically useful in patients with HCC less than 4 in number and less than 3
      cm in diameter. However, since multiple or large tumors are associated with low
      tumor-free survival or high local recurrence rates, PEIT for these tumors and the
      subsequent post-treatment follow-up should be performed carefully.

PMID- 14695708
TI  - [Prediction of hepatic fibrosis using serum hyaluronic acid in patients with
      chronic liver disease].
AB  - BACKGROUND/AIMS: The extent of hepatic fibrosis is important in chronic liver
      disease. Liver biopsy is essential for diagnosis of fibrosis. However, biopsy is
      invasive and may not represent the whole liver state. Serum hyaluronic acid (HA),
      a major component of connective tissues, was introduced as a useful non-invasive
      index of hepatic fibrosis. The aim of this study was to evaluate the relationship
      among HA, the degree of fibrosis, several hematologic and biochemical parameters
      in patients with chronic liver diseases or post state liver transplantation
      (PSLT). METHODS: Total 102 cases were divided into 4 groups: 57 chronic hepatitis
      (CH), 12 cirrhosis, 21 hepatocellular carcinoma (HCC), 12 PSLT. HA was measured
      by enzyme-linked binding protein assay and evaluated in relation the degree of
      fibrosis, several hematologic and biochemical parameters. RESULTS: Among four
      groups, HCC showed the highest HA and HA of HCC significantly higher than that of
      CH. The degree of fibrosis were correlated with HA. HA was correlated with age,
      platelet count and albumin but, not with ALT and PT. There is no significant
      relation between HA and the presence of acute rejection in liver transplantation.
      CONCLUSIONS: In chronic liver diseases, HA is a useful non-invasive index of
      hepatic fibrosis and disease severity.

PMID- 14695709
TI  - [Altered cholecystokinin-induced calcium signal in streptozotocin-induced
      diabetic rat pancreatic acini].
AB  - BACKGROUND/AIMS: Pancreatic acini of streptozotocin (STZ)-induced diabetic rats
      release amylase less than normal acini on cholecystokinin (CCK) stimulation.
      Pancreatic enzyme secretion has been closely related to the intracellular calcium
      concentration ([Ca2(+)](i)) of the acinar cell. In the present study, sequential
      changes of the intracellular calcium signal which probably underlie the altered
      enzyme secretion in response to CCK-8 were investigated using pancreatic acini
      from diabetic rats. METHODS: Diabetic rats were prepared by single intravenous
      injection of STZ (70 mg/kg). Stimulating experiments with CCK-8 were performed 7
      days later. Pancreatic acini were isolated by collagenase digestion. Amylase
      release and [Ca2(+)](i) were measured by colorimethod and calcium imaging,
      respectively. The geometry of intracellular calcium signal was analyzed. RESULTS:
      Normal acini exhibited concentration-dependent [Ca2(+)](i) increase and regular
      oscillatory calcium signal on CCK-8 stimulation. Amylase release was also
      concentration-dependent. However, diabetic acini showed significantly less
      [Ca2(+)](i) increase, prolonged time to peak [Ca2(+)](i), decreased calcium
      spikes number, and decreased amylase release compared with normal acini. The
      decreased [Ca2(+)](i) in diabetic acini was restored significantly by insulin
      treatment. CONCLUSIONS: Relatively decreased amylase release in diabetic
      pancreatic acini in response to CCK, appears to be associated with altered
      calcium signal due to insulin deficiency.

PMID- 14695710
TI  - [A case of enteropathy-associated T-cell lymphoma presenting with recurrent
      hematochezia].
AB  - Enteropathy-associated T-cell lymphoma (EATL) is an unusual primary
      gastrointestinal lymphoma, particularly associated with celiac sprue. This tumor
      usually affects the jejunum and grossly presents as multiple circumferential
      ulcers without the formation of definite tumor masses. Moreover, mesenteric lymph
      nodes are commonly involved. The patients have typically suffered from abdominal
      pain, diarrhea, or weight loss whereas some patients may manifest with
      nonspecific symptoms for a period of years or an acute emergency of perforation,
      obstruction, or hemorrhage. The clinical course of EATL is very unfavorable and
      the prognosis is poor. Both celiac sprue and EATL are very rare diseases in Asia,
      except India and Middle East. We report a 60-year-old male diagnosed as having
      EATL after segmental small bowel resection, who presented with recurrent
      gastrointestinal bleeding.

PMID- 14695711
TI  - [A case of double primary cancer: early gastric adenocarcinoma associated with
      adenocarcinoma and carcinoid].
AB  - Carcinoid tumors show variety of pathological features and some of them are
      admixed with adenocarcinoma. The carcinoma-carcinoid spectrum is a concept of
      classifying tumors based on the tumor mass differentiation which is composed of
      tissues of both endocrine and nonendocrine functions. When two types of tissues
      exist within one tumor intermingled with each other in a similar proportion, it
      is called composite tumor. On the other hand, collision tumor is characterized by
      the presence of two localized tissue types adjacently together. Gastric composite
      tumors are relatively rare. According to the reports on the Korean literature,
      there are several collision tumors, but only one case of gastric composite tumor
      has been cited. Reports of multiple synchronous or metachronous cancers have
      increased steadily during the last decades. Multiple gastric carcinoids or
      carcinoid tumors developed in association with gastric adenocarcinoma contribute
      to this trend. We report one case of gastric composite tumor simultaneously
      occurring with a early gastric adenocarcinoma with review of the literature.

PMID- 14695712
TI  - [A case of lower esophageal muscular ring presenting with dysphagia].
AB  - There are diverse ring-like narrowings in the lower esophagus: mucosal ring,
      muscular ring, ring-like annular peptic stricture. Esophageal muscular ring is
      extremely rare and generally asymptomatic. It occurs at the proximal border of
      the esophageal vestibule that corresponds to the upper end of the lower
      esophageal sphincter. We experienced a case of lower esophageal muscular ring
      with a symptom of intermittent mild dysphagia for 40 years and report the
      findings with a review of the literature.

PMID- 14695713
TI  - [Acute gastric volvulus due to diaphragmatic hernia].
AB  - Gastric volvulus is an uncommon condition which is difficult to diagnose and
      treat. It designates abnormal rotation of the stomach along its longitudinal
      (organoaxial) or transverse (mesenteroaxial) axis. When the rotation exceeds 180
      degrees, gastric obstruction or strangulation may occur. The classical
      presentation of acute gastric volvulus is the triad of severe epigastric pain,
      vomiting followed by retching without the ability to vomit, and difficulty or
      inability to pass a nasogastric tube. Delay in diagnosis and treatment of gastric
      volvulus can lead to fatal complications such as gastric ischemia, perforation,
      and hemorrhage. Gastric volvulus is a true emergency which should be treated
      immediately either surgically or by upper endoscopy. We report a case of an acute
      incarcerated gastric volvulus due to a left-sided diaphragmatic hernia in an
      adult male patient, which was treated successfully by operation.

PMID- 14695714
TI  - The times are a-changin': should we hang up the stethoscope?

PMID- 14695715
TI  - The case for pediatric drug development in clinical pain research.

PMID- 14695716
TI  - Is there any reason to withhold beta blockers from high-risk patients with
      coronary artery disease during surgery?

PMID- 14695718
TI  - Comparative diagnostic performances of auscultation, chest radiography, and lung
      ultrasonography in acute respiratory distress syndrome.
AB  - BACKGROUND: Lung auscultation and bedside chest radiography are routinely used to
      assess the respiratory condition of ventilated patients with acute respiratory
      distress syndrome (ARDS). Clinical experience suggests that the diagnostic
      accuracy of these procedures is poor. METHODS: This prospective study of 32
      patients with ARDS and 10 healthy volunteers was performed to compare the
      diagnostic accuracy of auscultation, bedside chest radiography, and lung
      ultrasonography with that of thoracic computed tomography. Three pathologic
      entities were evaluated in 384 lung regions (12 per patient): pleural effusion,
      alveolar consolidation, and alveolar-interstitial syndrome. RESULTS: Auscultation
      had a diagnostic accuracy of 61% for pleural effusion, 36% for alveolar
      consolidation, and 55% for alveolar-interstitial syndrome. Bedside chest
      radiography had a diagnostic accuracy of 47% for pleural effusion, 75% for
      alveolar consolidation, and 72% for alveolar-interstitial syndrome. Lung
      ultrasonography had a diagnostic accuracy of 93% for pleural effusion, 97% for
      alveolar consolidation, and 95% for alveolar-interstitial syndrome. Lung
      ultrasonography, in contrast to auscultation and chest radiography, could
      quantify the extent of lung injury. Interobserver agreement for the ultrasound
      findings as assessed by the kappa statistic was satisfactory: 0.74, 0.77, and
      0.73 for detection of alveolar-interstitial syndrome, alveolar consolidation, and
      pleural effusion, respectively. CONCLUSIONS: At the bedside, lung ultrasonography
      is highly sensitive, specific, and reproducible for diagnosing the main lung
      pathologic entities in patients with ARDS and can be considered an attractive
      alternative to bedside chest radiography and thoracic computed tomography.

PMID- 14695719
TI  - Noninvasive positive pressure ventilation using a helmet in patients with acute
      exacerbation of chronic obstructive pulmonary disease: a feasibility study.
AB  - BACKGROUND: Noninvasive positive pressure ventilation (NPPV) with a facemask (FM)
      is effective in patients with acute exacerbation of their chronic obstructive
      pulmonary disease. Whether it is feasible to treat these patients with NPPV
      delivered by a helmet is not known. METHODS: Over a 4-month period, the authors
      studied 33 chronic obstructive pulmonary disease patients with acute exacerbation
      who were admitted to four intensive care units and treated with helmet NPPV. The
      patients were compared with 33 historical controls treated with FM NPPV, matched
      for simplified acute physiologic score (SAPS II), age, PaCO2, pH, and
      PaO2:fractional inspired oxygen tension. The primary endpoints were the
      feasibility of the technique, improvement of gas exchange, and need for
      intubation. RESULTS: The baseline characteristics of the two groups were similar.
      Ten patients in the helmet group and 14 in the FM group (P = 0.22) were
      intubated. In the helmet group, no patients were unable to tolerate NPPV, whereas
      five patients required intubation in the FM group (P = 0.047). After 1 h of
      treatment, both groups had a significant reduction of PaCO2 with improvement of
      pH; PaCO2 decreased less in the helmet group (P = 0.01). On discontinuing
      support, PaCO2 was higher (P = 0.002) and pH lower (P = 0.02) in the helmet group
      than in the control group. One patient in the helmet group, and 12 in the FM
      group, developed complications related to NPPV (P < 0.001). Length of intensive
      care unit stay, intensive care unit, and hospital mortality were similar in both
      groups. CONCLUSIONS: Helmet NPPV is feasible and can be used to treat chronic
      obstructive pulmonary disease patients with acute exacerbation, but it does not
      improve carbon dioxide elimination as efficiently as does FM NPPV.

PMID- 14695720
TI  - Gum elastic bougie-guided insertion of the ProSeal laryngeal mask airway is
      superior to the digital and introducer tool techniques.
AB  - BACKGROUND: The authors compare three techniques for insertion of the ProSeal
      laryngeal mask airway. METHODS: Two hundred forty healthy patients aged 18-80 yr
      were randomly allocated for ProSeal laryngeal mask airway insertion using the
      digital, introducer tool (IT), or gum elastic bougie (GEB)-guided techniques. The
      digital and IT techniques were performed according to the manufacturer's
      instructions. The GEB-guided technique involved priming the drain tube with the
      GEB, placing the GEB in the esophagus under direct vision, and inserting the
      ProSeal laryngeal mask airway using the digital technique with the GEB as a
      guide. Failed insertion was defined by any of the following criteria: (1) failed
      pharyngeal placement; (2) malposition (air leaks, negative tap test results, or
      failed gastric tube insertion if pharyngeal placement was successful); and (3)
      ineffective ventilation (maximum expired tidal volume < 8 ml/kg or end-tidal
      carbon dioxide > 45 mmHg if correctly positioned). Any visible or occult blood
      was noted. Sore throat, dysphonia, and dysphagia were assessed 18-24 h
      postoperatively. RESULTS: Insertion was more frequently successful with the GEB
      guided technique at the first attempt (GEB, 100%; digital, 88%; IT, 84%; both P <
      0.001), but success after three attempts was similar (GEB, 100%; digital, 99%;
      IT, 98%). The time taken to successful placement was similar among groups at the
      first attempt but was shorter for the GEB-technique after three attempts (GEB, 25
      +/- 14 s; digital, 33 +/- 19 s; IT, 37 +/- 25 s; both: P < 0.003). There were no
      differences in the frequency of visible blood, but occult blood occurred less
      frequently with the GEB-guided technique (GEB, 12%; digital, 29%; IT, 31%; both:
      P < 0.02) but was similar among techniques if insertion was successful at the
      first attempt. There were no differences in postoperative airway morbidity.
      CONCLUSION The GEB-guided insertion technique is more frequently successful than
      the digital or IT techniques. The authors suggest that the GEB-guided technique
      may be a useful backup technique for when the digital and IT techniques fail.

PMID- 14695721
TI  - High incidence of myocardial ischemia during postpartum hemorrhage.
AB  - BACKGROUND: Postpartum hemorrhage remains a major cause of global maternal
      morbidity and mortality, even in developed countries, despite the use of
      intensive care units. This study sought to (1) assess whether myocardial ischemia
      could be associated with and even aggravate hemorrhagic shock in young
      parturients admitted for postpartum hemorrhage, and (2) identify the independent
      risk factors for myocardial ischemia. METHODS: On their referral to the intensive
      care unit, a multidisciplinary team managed parturients with severe postpartum
      hemorrhage. Ventilation, transfusion, catecholamines, surgery, or angiography
      with uterine embolization were provided as clinically indicated. Plasma cardiac
      troponin I levels were used as a surrogate marker of acute myocardial injury and
      electrocardiograms of myocardial ischemia. RESULTS: A total of 55 parturients
      were referred with severe postpartum hemorrhage, all in hemorrhagic shock. Twenty
      eight parturients (51%) had elevated serum levels of cardiac troponin I (9.4
      microg/l [3.7-26.6 microg/l]), which were associated with electrocardiographic
      signs of ischemia and deteriorated myocardial contractility and correlated with
      the severity of hemorrhagic shock. Indeed, multivariate analysis identified low
      systolic and diastolic arterial blood pressure (< 88 and < 50 mmHg, respectively)
      and increased heart rate (> 115 beats/min) as independent predictors of
      myocardial injury. In addition, all patients who were given catecholamines also
      had elevated cardiac troponin I levels. CONCLUSIONS: These results suggest that
      treatment of postpartum hemorrhage-induced hemorrhagic shock should be coupled
      with concomitant prevention of myocardial ischemia, even in young parturients.

PMID- 14695722
TI  - Nefopam, a nonsedative benzoxazocine analgesic, selectively reduces the shivering
      threshold in unanesthetized subjects.
AB  - BACKGROUND: The analgesic nefopam does not compromise ventilation, is minimally
      sedating, and is effective as a treatment for postoperative shivering. The
      authors evaluated the effects of nefopam on the major thermoregulatory responses
      in humans: sweating, vasoconstriction, and shivering. METHODS: Nine volunteers
      were studied on three randomly assigned days: (1) control (saline), (2) nefopam
      at a target plasma concentration of 35 ng/ml (low dose), and (3) nefopam at a
      target concentration of 70 ng/ml (high dose, approximately 20 mg total). Each
      day, skin and core temperatures were increased to provoke sweating and then
      reduced to elicit peripheral vasoconstriction and shivering. The authors
      determined the thresholds (triggering core temperature at a designated skin
      temperature of 34 degrees C) by mathematically compensating for changes in skin
      temperature using the established linear cutaneous contributions to control of
      each response. RESULTS: Nefopam did not significantly modify the slopes for
      sweating (0.0 +/- 4.9 degrees C. microg-1. ml; r2 = 0.73 +/- 0.32) or
      vasoconstriction (-3.6 +/- 5.0 degrees C. microg-1. ml; r2 = -0.47 +/- 0.41). In
      contrast, nefopam significantly reduced the slope of shivering (-16.8 +/- 9.3
      degrees C. microg-1. ml; r2 = 0.92 +/- 0.06). Therefore, high-dose nefopam
      reduced the shivering threshold by 0.9 +/- 0.4 degrees C (P < 0.001) without any
      discernible effect on the sweating or vasoconstriction thresholds. CONCLUSIONS:
      Most drugs with thermoregulatory actions-including anesthetics, sedatives, and
      opioids-synchronously reduce the vasoconstriction and shivering thresholds.
      However, nefopam reduced only the shivering threshold. This pattern has not
      previously been reported for a centrally acting drug. That pharmacologic
      modulations of vasoconstriction and shivering can be separated is of clinical and
      physiologic interest.

PMID- 14695723
TI  - Monitoring of immobility to noxious stimulation during sevoflurane anesthesia
      using the spinal H-reflex.
AB  - BACKGROUND: The spinal H-reflex has been shown to correlate with surgical
      immobility, i.e., the absence of motor responses to noxious stimulation, during
      isoflurane anesthesia. Here, the authors established individual concentration
      response functions for H-reflex amplitude and tested the predictive power of the
      H-reflex for movement responses during sevoflurane anesthesia in comparison to
      electroencephalographic parameters. In addition, they investigated the effect of
      noxious stimulation on the H-reflex itself. METHODS: The authors studied 12
      female patients during sevoflurane anesthesia before surgery. The sevoflurane
      concentration was increased, a laryngeal mask was inserted, and then the
      sevoflurane concentration was decreased until H-reflex amplitude (recorded over
      the soleus muscle) recovered. Thereafter, the end-tidal sevoflurane concentration
      was kept at a constant value close to the minimum alveolar concentration for
      suppression of movement responses after tetanic stimulation (MACtetanus),
      determined by the Dixon up-down method. Pharmacodynamic modeling of H-reflex
      amplitude and of the Bispectral Index was performed, and predictive values for
      motor responses to noxious electrical stimulation (50 Hz, 60 mA tetanus, volar
      forearm) were compared using the prediction probability. RESULTS: Concentration
      dependent depression of H-reflex amplitude by sevoflurane was well modeled
      (median r2 = 0.97) by a sigmoid function with a median EC50 of 1.5 vol% and a
      median slope parameter of 3.7, much steeper than the slope for the Bispectral
      Index. MACtetanus calculated by logistic regression was 1.6 vol%. H-reflex
      amplitude predicted motor responses to noxious stimulation with a prediction
      probability of 0.76, whereas the prediction probability for Bispectral Index and
      spectral edge frequency (SEF95) were not different from chance alone. Noxious
      stimulation was followed by a substantial increase of H-reflex amplitude for
      several minutes, whereas the Bispectral Index and SEF95 exhibited no significant
      changes. CONCLUSIONS: Suppression of movement to noxious stimulation and
      suppression of H-reflex amplitude by sevoflurane follow similar concentration
      response functions. Although this does not imply a causal relation, it explains
      the high predictive value of H-reflex amplitude for motor responses to noxious
      stimuli, even in a narrow concentration range around the MACtetanus.

PMID- 14695724
TI  - Albumin and hydroxyethyl starch modulate oxidative inflammatory injury to
      vascular endothelium.
AB  - BACKGROUND: Human serum albumin is used clinically to maintain colloid osmotic
      pressure and is viewed to serve an antioxidant role in the vascular compartment
      via binding of redox-active metal complexes, transport of nitric oxide, and the
      oxidant-scavenging reactions of the single thiol of human serum albumin, cys34.
      Because of these potentially desirable adjunctive actions, we evaluated the
      purity and thiol redox state and compared the relative effects of clinically
      available 25% human serum albumin preparations with a starch-derived colloid, 6%
      hydroxyethyl starch, in in vitro models of inflammatory vascular injury. METHODS:
      Bovine aortic endothelial cell responses to chemical, enzymatic, and cell-derived
      reactive inflammatory mediators in the presence of human serum albumin or
      hydroxyethyl starch were assessed. RESULTS: The cys34 thiol of fresh human serum
      albumin preparations was 70-85% oxidized and contained a population of human
      serum albumin (approximately 25% of total) having the cys34 resistant to
      reduction by 2-mercaptoethanol and NaBH4. Treatment of bovine aortic endothelial
      cells with human serum albumin dose-dependently protected from HOCl-mediated 14C
      adenine release, with this protective effect of human serum albumin not dependent
      on protein thiol status. Addition of human serum albumin to cell media provided
      no protection from the cytotoxic actions of peroxynitrite and xanthine oxidase
      derived reactive species. Binding of activated polymorphonuclear leukocytes to
      bovine aortic endothelial cells was significantly amplified by hydroxyethyl
      starch and inhibited by human serum albumin administration. The binding of
      neutrophil-derived myeloperoxidase to bovine aortic endothelial cells, a mediator
      of multiple oxidative and nitric oxide-consuming reactions, was also inhibited by
      human serum albumin and enhanced by hydroxyethyl starch. CONCLUSIONS: Clinical
      human serum albumin preparations show modest intrinsic non-thiol-dependent
      antiinflammatory properties in vitro, a phenomenon that was not observed with
      hydroxyethyl starch.

PMID- 14695725
TI  - Differential activation of mitogen-activated protein kinases in ischemic and
      anesthetic preconditioning.
AB  - BACKGROUND: Accumulating evidence pinpoints to the pivotal role of mitogen
      activated protein kinases (MAPKs) in the signal transduction underlying cardiac
      preconditioning. METHODS: PD98059, an inhibitor of extracellular signal-regulated
      protein kinase (MEK-ERK1/2), and SB203580, an inhibitor of p38 MAPK, were used to
      evaluate the role of MAPKs with respect to postischemic functional recovery in
      isolated perfused rat hearts subjected to ischemic preconditioning (IPC) and
      anesthetic preconditioning (APC). Western blot analyses were used to determine
      the degree of ERK1/2 and p38 MAPK activation after the application of the
      preconditioning stimulus and after ischemia-reperfusion. Immunohistochemical
      staining served to visualize subcellular localization of activated MAPKs.
      RESULTS: PD98059 and SB203580 abolished postischemic functional recovery in IPC
      but not in APC. IPC but not APC markedly activated ERK1/2 and p38 MAPK, which
      were abrogated by coadministration of the specific blockers. Conversely, IPC and
      APC enhanced ERK1/2 activity after ischemia-reperfusion as compared to
      nonpreconditioned hearts, and IPC in addition enhanced p38 MAPK activity.
      Coadministration of PD98059 and SB203580 during IPC but not during APC inhibited
      postischemically enhanced MAPK activities. Moreover, chelerythrine and 5
      hydroxydecanoate, effective blockers of IPC and APC, annihilated IPC- and APC
      induced enhanced postischemic responses of MAPKs. Finally, administration of
      PD98059 during ischemia-reperfusion diminished the protective effects of IPC and
      APC. Immunohistochemistry revealed increased ERK1/2 activity primarily in
      intercalated discs and nuclei and increased p38 MAPK activity in the sarcolemma
      and nuclei of IPC-treated hearts. CONCLUSIONS: Although MAPKs may orchestrate
      cardioprotection as triggers and mediators in IPC, they are devoid of triggering,
      but they may have mediator effects in APC.

PMID- 14695726
TI  - Hyperoxic ventilation reduces 6-hour mortality at the critical hemoglobin
      concentration.
AB  - BACKGROUND: Acute normovolemic hemodilution reduces the circulating erythrocyte
      mass and, thus, the hemoglobin concentration. After extreme acute normovolemic
      hemodilution to the critical hemoglobin concentration (Hbcrit), oxygen demand of
      the tissues is no longer met by oxygen supply, and death occurs with increasing
      oxygen debt. The aim of the current study was to investigate whether ventilation
      with 100% oxygen (fraction of inspired oxygen [FiO2] = 1.0; hyperoxic
      ventilation) initiated at Hbcrit could restore adequate tissue oxygenation and
      prevent death. METHODS: Fourteen anesthetized pigs ventilated with room air (FiO2
      = 0.21) were hemodiluted by exchange of whole blood for 6% hydroxyethyl starch
      (200,000:0.5) until the individual Hbcrit was reached. Hbcrit was defined as the
      onset of oxygen supply dependency of oxygen consumption and was identified with
      indirect calorimetry. For the next 6 h, animals were either ventilated with an
      FiO2 of 0.21 (n = 7) or an FiO2 of 1.0 (n = 7). RESULTS: All animals in the 0.21
      FiO2 group died within the first 3 h at Hbcrit (i.e., 6-h mortality 100%). Death
      was preceded by an increase of serum concentrations of lactate and
      catecholamines. In contrast to that, six of the seven animals of the 1.0 FiO2
      group survived the complete 6-h observation period without lactacidosis and
      increased serum catecholamines (i.e., 6-h mortality 14%; FiO2 0.21 vs. FiO2 1.0,
      P < or = 0.05). After 6 h at Hbcrit, the FiO2 was reduced from 1.0 to 0.21, and
      five of the six animals died within the next 3 h. CONCLUSION: In anesthetized
      pigs submitted to lethal anemia, hyperoxic ventilation enabled survival for 6 h
      without signs of circulatory failure.

PMID- 14695727
TI  - Surfactants attenuate gas embolism-induced thrombin production.
AB  - BACKGROUND: There are no pharmacologic strategies to prevent embolism bubble
      induced blood clot formation. The authors conducted experiments to measure
      thrombin production in sheared whole blood in the presence and absence of bubbles
      and three surface-active compounds. METHODS: Blood samples were obtained from six
      volunteers seven times. The thrombin-specific substrate Boc-VPR-MCA was added to
      citrated blood diluted with HEPES-buffered saline. Experimental groups were as
      follows: sparging (air microbubble embolization) with surfactant present;
      sparging alone; surfactant alone; and neither surfactant nor sparging. The
      surfactants were Dow Corning Antifoam 1510US, Perftoran, and Pluronic F-127.
      Blood was sheared by a cone-plate viscometer at 100 and 500 s-1 for 5, 10, and 20
      min at 37 degrees C, pipetted into excess stop buffer, and evaluated
      fluorimetrically. Mean values of fluorescence intensity +/- SDs for each group
      were compared using ANOVA. Differences were considered significant at P < 0.05
      using the Bonferroni correction. RESULTS: For fixed shear rate, thrombin
      production increased 2.3- to 5.7-fold (P < 0.05) as shear duration lengthened.
      For fixed shear duration, thrombin production increased 1.9- to 3.9-fold (P <
      0.05) with increasing shear rate. For fixed shear rate and duration, sparging
      increased thrombin production 2.1- to 3.7-fold (P < 0.05). Surfactant addition
      without sparging did not change thrombin production (P > 0.05). Surfactants
      attenuated thrombin production in sparged samples 31.8-70.9% (P < 0.05).
      CONCLUSIONS: Thrombin production is shear rate and duration-dependent. Sparging
      increases thrombin production. Surfactants added before sparging attenuate
      thrombin production. Surfactants may have a clinical application to attenuate gas
      embolism-induced clotting.

PMID- 14695728
TI  - Sodium bisulfite: scapegoat for chloroprocaine neurotoxicity?
AB  - BACKGROUND: Neurologic deficits after apparent intrathecal injection of 3%
      Nesacaine-CE intended for epidural administration created concern about the
      potential toxicity of chloroprocaine and the preservative sodium bisulfite.
      Although bisulfite-free formulations of chloroprocaine were subsequently
      introduced into clinical practice, the relative toxicities of this anesthetic and
      preservative were never clearly established. The current studies used a relevant
      functional and histologic model to investigate the intrathecal neurotoxicity of
      these two compounds. METHODS: In the first experiment, rats implanted with
      intrathecal catheters were given one of two commercially available solutions of
      chloroprocaine, one of which contained sodium bisulfite; control animals received
      saline. Animals were assessed for sensory impairment 7 days after administration
      using the tail-flick test and were killed to obtain histologic specimens to
      quantify nerve injury. In the second experiment, identical methodology was used
      to investigate the effects of freshly prepared solutions of chloroprocaine,
      chloroprocaine with sodium bisulfite, sodium bisulfite, and saline. RESULTS: The
      two experiments yielded similar results. In experiment 1, tail-flick latencies
      and nerve injury scores after administration of plain chloroprocaine were
      significantly greater than those of chloroprocaine containing bisulfite. Injury
      scores for animals receiving chloroprocaine with bisulfite were elevated compared
      with those for animals given saline. In experiment 2, animals receiving plain
      chloroprocaine developed elevations in tail-flick latencies and nerve injury
      scores that were significantly greater than those for all other groups. Nerve
      injury scores with chloroprocaine containing bisulfite were greater than with
      saline or bisulfite alone. Tail-flick latencies and nerve injury scores with
      bisulfite alone were similar to those with saline. CONCLUSIONS: Clinical deficits
      associated with unintentional intrathecal injection of chloroprocaine likely
      resulted from a direct effect of the anesthetic, not the preservative. The data
      also suggest that bisulfite can reduce neurotoxic damage induced by intrathecal
      local anesthetic.

PMID- 14695729
TI  - Developmental regulation of codeine analgesia in the rat.
AB  - BACKGROUND: Codeine analgesia is dependent on metabolism to morphine. Metabolic
      capability is genetically determined in rats and humans, and individuals can be
      classified as extensive or poor metabolizers, as determined by the extent of
      production of morphine. Codeine is often given to infants and children. The aim
      of this study was to investigate the effects of developmental age on codeine
      analgesia in rats. METHODS: The effects of codeine were compared with those of
      morphine using withdrawal reflex responses to mechanical stimuli (with and
      without inflammation) and to noxious heat in two strains of rats (Sprague-Dawley
      and Dark Agouti) that have been used to model human metabolic phenotypes because
      of marked differences in enzyme activity. Effects of the opioids were compared at
      3, 10, and 21 days of age and in adult rats. RESULTS: Consistent age-related
      changes in the efficacy of codeine relative to morphine were noted for both
      strains of rats. For the extensive metabolizer (Sprague-Dawley) strain, codeine
      efficacy was substantially lower at 3 days of age (P < 0.001), but there was no
      difference between the effects of codeine and morphine for 10- and 21-day-old
      rats and adults (P > 0.05). Poor metabolizers (Dark Agouti strain) also had
      comparatively low efficacy for codeine compared with morphine in 3-day-old rats
      and in adults (P < 0.001). In 10- and 21-day-old Dark Agouti rats, there was no
      difference between either drug (P < 0.05). CONCLUSIONS: Codeine analgesia is
      developmentally regulated, with low efficacy in the early postnatal period.
      Effects in the adult rat were not predictive of efficacy in development in either
      strain, which has important implications for further study and, possibly, for
      clinical use.

PMID- 14695730
TI  - Chronic pain management: American Society of Anesthesiologists Closed Claims
      Project.
AB  - BACKGROUND: The practice of chronic pain management has grown steadily in recent
      years. The purpose of this study was to identify and describe issues and trends
      in liability related to chronic pain management by anesthesiologists. METHODS:
      Data from 5,475 claims in the American Society of Anesthesiologists Closed Claims
      Project database between 1970 and 1999 were reviewed to compare liability related
      to chronic pain management with that related to surgical and obstetric
      (surgical/obstetric) anesthesia. Acute pain management claims were excluded from
      analysis. Outcomes and liability characteristics between 284 pain management
      claims and 5,125 surgical/obstetric claims were compared. RESULTS: Claims related
      to chronic pain management increased over time (P < 0.01) and accounted for 10%
      of all claims in the 1990s. Compensatory payment amounts were lower in chronic
      pain management claims than in surgical/obstetric anesthesia claims from 1970 to
      1989 (P < 0.05), but during the 1990s, there was no difference in size of
      payments. Nerve injury and pneumothorax were the most common outcomes in invasive
      pain management claims. Epidural steroid injections accounted for 40% of all
      chronic pain management claims. Serious injuries, involving brain damage or
      death, occurred with epidural steroid injections with local anesthetics and/or
      opioids and with maintenance of implantable devices. CONCLUSIONS: Frequency and
      payments of claims associated with chronic pain management by anesthesiologists
      increased in the 1990s. Brain damage and death were associated with epidural
      steroid injection only when opioids or local anesthetics were included.
      Anesthesiologists involved in home care of patients with implanted devices such
      as morphine pumps and epidural injections or patient-controlled analgesia should
      be aware of potential complications that may have severe outcomes.

PMID- 14695731
TI  - Influence of lumbosacral cerebrospinal fluid density, velocity, and volume on
      extent and duration of plain bupivacaine spinal anesthesia.
AB  - BACKGROUND: The current study was designed to investigate the influence of
      lumbosacral cerebrospinal fluid (CSF) density, velocity, and volume on the extent
      and duration of plain bupivacaine spinal anesthesia. METHODS: Forty-one patients
      scheduled to undergo orthopedic surgery with spinal block were enrolled.
      Lumbosacral CSF volumes were calculated from low thoracic, lumbar, and sacral
      axial magnetic resonance images. CSF velocity at the L3-L4 level was derived from
      phase-contrast magnetic resonance images. Spinal anesthesia was performed in the
      lateral decubitus position. CSF (2 ml) was sampled to measure CSF density before
      injection of 3 ml plain bupivacaine (0.5%). Statistical correlation coefficients
      (rho) between CSF characteristics and measurements of spinal anesthesia were
      assessed by Spearman rank correlation. In addition, stepwise multiple linear
      regression models were used to select important predictors of measures of spinal
      anesthesia. RESULTS: There was a significant correlation between CSF density and
      peak sensory block level (rho = 0.33, P = 0.034). Lumbosacral CSF volume
      inversely correlated with peak sensory block level (rho = -0.65, P < 0.0001) and
      positively correlated with onset time of complete motor block (rho = 0.42, P =
      0.008). CSF volume also inversely correlated with time required for regression of
      the sensory block to L1 (rho = -0.35, P = 0.026) and L2 (rho = -0.33, P = 0.039).
      There was a significant inverse correlation between peak diastolic CSF velocity
      and duration of motor blockade (rho = -0.44, P = 0.005). Multiple regression
      analysis revealed that weight and CSF volume significantly contributed to the
      peak sensory block level (R2 = 0.46). CONCLUSIONS: These findings indicate that
      CSF density and volume influence the spread of spinal anesthesia with plain
      bupivacaine and that CSF volume also influences the duration of spinal
      anesthesia. CSF velocity might also influence the duration of plain bupivacaine
      spinal anesthesia.

PMID- 14695732
TI  - Prediction of postoperative pain by preoperative nociceptive responses to heat
      stimulation.
AB  - BACKGROUND: Despite major advances in the understanding of the neurobiologic
      mechanisms of pain, the wide variation in acute pain experience has not been well
      explained. Therefore, the authors investigated the potential of a preoperatively
      induced heat injury to predict subsequent postoperative pain ratings in patients
      undergoing knee surgery. METHODS: Twenty patients were studied. The burn injury
      was induced 6 days before surgery with a contact thermode (12.5 cm2, 47 degrees C
      for 7 min). The sensory testing, before and 1 h after the injury, included pain
      score during induction of the burn, secondary hyperalgesia area, thermal and
      mechanical pain perception, and pain thresholds. Postoperative analgesia
      consisted of ibuprofen and acetaminophen. Pain ratings (visual analog scale) at
      rest and during limb movement were followed for 10 days after surgery. RESULTS:
      The burn injury was associated with development of significant hyperalgesia.
      There was a significant correlation between preoperative pain ratings during the
      burn injury and early (0-2 days, area under the curve) and late (3-10 days, area
      under the curve) postoperative dynamic pain ratings during limb movement.
      CONCLUSION: The results of this study suggest that the pain response to a
      preoperative heat injury may be useful in research in predicting the intensity of
      postoperative pain. These findings may have important implications to identify
      patients at risk for development of chronic pain and to stratify individuals for
      investigations of new analgesics.

PMID- 14695733
TI  - Pharmacokinetic-pharmacodynamic modeling of morphine-6-glucuronide-induced
      analgesia in healthy volunteers: absence of sex differences.
AB  - BACKGROUND: Morphine-6-glucuronide (M6G) is a metabolite of morphine and a micro
      opioid agonist. To quantify the potency and speed of onset-offset of M6G and
      explore putative sex dependency, the authors studied the pharmacokinetics and
      pharmacodynamics of M6G in volunteers using a placebo-controlled, randomized,
      double-blind study design. METHODS: Ten men and 10 women received 0.3 mg/kg
      intravenous M6G and placebo (two thirds of the dose as bolus, one third as a
      continuous infusion over 1 h) on separate occasions. For 7 h, pain tolerance was
      measured using gradually increasing transcutaneous electrical stimulation, and
      blood samples were obtained. A population pharmacokinetic (inhibitory sigmoid
      Emax)-pharmacodynamic analysis was used to analyze M6G-induced changes in
      tolerated stimulus intensity. The improvement in model fits by inclusion of
      covariate sex was tested for significance. P values less than 0.01 were
      considered significant. Taking into account previous morphine data, a predictive
      pharmacokinetic-pharmacodynamic model was constructed to determine the
      contribution of M6G to morphine analgesia. RESULTS: M6G concentrations did not
      differ between men and women. M6G caused analgesia significantly greater than
      that observed with placebo (P < 0.01). The M6G analgesia data were well described
      by the pharmacokinetic-pharmacodynamic model. The M6G effect site concentration
      causing a 25% increase in current (C25) was 275 +/- 135 nm (population estimate
      +/- SE), the blood effect site equilibration half-life was 6.2 +/- 3.3 h, and the
      steepness parameter was 0.71 +/- 0.18. Intersubject variability was 167% for C25
      and 218% for the effect half-life. None of the model parameters showed sex
      dependency. CONCLUSIONS: A cumulative dose of 0.3 mg/kg M6G, given over 1 h,
      produces long-term analgesia greater than that observed with placebo, with equal
      dynamics (potency and speed of onset-offset) in men and women. Possible causes
      for the great intersubject response variability, such as genetic polymorphism of
      the micro-opioid receptor and placebo-related phenomena, are discussed. The
      predictive pharmacokinetic-pharmacodynamic model was applied successfully and was
      used to estimate M6G analgesia after morphine in patients with normal and
      impaired renal function.

PMID- 14695734
TI  - Effects of perioperative oral amantadine on postoperative pain and morphine
      consumption in patients after radical prostatectomy: results of a preliminary
      study.
AB  - BACKGROUND: Amantadine is known to be a noncompetitive N-methyl-D-aspartate
      receptor antagonist and may be useful in preventing postoperative central
      sensitization, acute opioid tolerance, and opioid-induced hyperalgesia, thereby
      decreasing pain and analgesic requirements. The aim of this pilot study was to
      evaluate the effects of perioperative oral amantadine on postoperative pain and
      analgesic consumption. METHODS: Twenty-four patients scheduled to undergo radical
      prostatectomy were given oral amantadine before and after surgery in a
      randomized, double-blind, placebo-controlled manner. After surgery, patients
      received intravenous patient-controlled analgesia with morphine for 48 h. Wound
      pain intensity, sensitivity to mechanical pressure around the surgical wound, and
      incidence of bladder spasm pain were assessed. Blood samples were drawn for
      analysis of amantadine, morphine, and the morphine metabolites. Adverse effects
      and patient satisfaction were assessed. RESULTS: The cumulative morphine
      consumption was significantly lower in the amantadine group at all time points
      (except at 48 h), amounting to a 32% reduction over the 48-h period. Forty-eight
      hours after surgery, visual analog pain scores to pressure applied near the wound
      were significantly lower in the amantadine group than in the placebo group. In
      addition, the number of patients reporting bladder spasm pain was significantly
      lower in the amantadine group. Plasma concentration of morphine-3-glucuronide was
      significantly lower at the end of surgery in the amantadine group.
      Pharmacokinetic analyses showed that the plasma clearance of morphine at 22-24 h
      after surgery was also significantly lower in the amantadine group. CONCLUSION:
      The results suggest that perioperative oral amantadine reduces postoperative
      opioid consumption by pharmacokinetic mechanisms, although additional
      pharmacodynamic interactions may also be involved.

PMID- 14695735
TI  - Labor analgesia and cesarean delivery: an individual patient meta-analysis of
      nulliparous women.
AB  - BACKGROUND: The authors performed an individual patient meta-analysis of 2,703
      nulliparous women who were randomized to either epidural analgesia or intravenous
      opioids for pain relief during labor from five trials conducted at their
      hospital. The primary purpose in this meta-analysis was to evaluate the effects
      of epidural analgesia during labor on the rate of cesarean delivery. METHODS:
      Between November 1, 1993, and November 3, 2000, 2,703 nulliparous women (2,188
      healthy parturients and 515 women with pregnancy-induced hypertension) in
      spontaneous labor at term were randomized to receive either epidural analgesia or
      intravenous opioid analgesia in the five studies. Epidural analgesia was
      initiated with either epidural bupivacaine or intrathecal sufentanil and was
      maintained with a low-dose (0.0625% or 0.125%) mixture of bupivacaine with
      fentanyl. Intravenous opioid analgesia was initiated with 50 mg meperidine and 25
      mg promethazine hydrochloride and was maintained with intravenous boluses of
      meperidine as needed. RESULTS: A total of 1,339 nulliparous women were randomized
      to receive epidural analgesia, and 1,364 women were randomized to receive
      intravenous meperidine analgesia. There was no difference in the rate of cesarean
      deliveries between the two analgesia groups (epidural analgesia, 10.5% [140 of
      1,339] vs. intravenous meperidine analgesia, 10.3% [141 of 1,364]; adjusted odds
      ratio, 1.04; 95% confidence interval, 0.81-1.34; P = 0.920). Significantly more
      women randomized to epidural analgesia had forceps deliveries compared to
      meperidine analgesia (13% [172 of 1,339] vs. 7% [101 of 1,364]; adjusted odds
      ratio, 1.86; 95% confidence interval, 1.43-2.40; P < 0.001). Epidural women had
      longer first and second stages of labor. Women who received epidural analgesia
      reported lower pain scores during labor and delivery compared to women who
      received intravenous meperidine analgesia. CONCLUSION: Epidural analgesia
      compared to intravenous meperidine analgesia during labor does not increase the
      number of cesarean deliveries.

PMID- 14695736
TI  - Mobilization of opioid-containing polymorphonuclear cells by hematopoietic growth
      factors and influence on inflammatory pain.
AB  - BACKGROUND: Leukocytes can control inflammatory pain by secretion of opioid
      peptides, stimulated by cold-water swimming or local injection of corticotropin
      releasing factor, and subsequent activation of opioid receptors on peripheral
      sensory neurons. This study investigated whether mobilization of
      polymorphonuclear cells (PMN) by granulocyte colony-stimulating factor (G-CSF)
      and stem cell factor (SCF) enhances immigration of opioid-containing PMN and
      peripheral opioid analgesia in rats with Freund complete adjuvant-induced hind
      paw inflammation. METHODS: In circulating PMN of rats treated with G-CSF+SCF and
      sham-treated rats, opioid peptide content was measured by radioimmunoassay.
      Expression of adhesion molecules (CD62L, CD49d, CD18), in vitro migration in the
      Boyden chamber, and infiltrating leukocytes were analyzed by flow cytometry.
      Chemokine messenger RNA transcription was quantified by LightCycler polymerase
      chain reaction. Paw pressure threshold was measured at baseline, after cold-water
      swimming, and after injection of corticotropin-releasing factor. RESULTS: G
      CSF+SCF treatment increased circulating PMN (11-fold, P < 0.05). Mobilized PMN
      had decreased content of beta-endorphin but not of Met-enkephalin per cell, down
      regulation of CD62L, up-regulation of CD49d (but no change in CD18), and reduced
      migration toward higher chemokine concentrations (all P < 0.05). In the paw, one
      of four chemokine messenger RNAs was significantly expressed during the first 2 h
      of inflammation (P < 0.05), immigration of PMN and opioid-containing cells was
      slightly increased (1.5-fold, P < 0.05), and baseline paw pressure threshold, as
      well as paw pressure threshold increases induced by corticotropin-releasing
      factor and cold-water swimming, were unchanged (P > 0.05). CONCLUSIONS: G-CSF+SCF
      mobilized circulating opioid-containing PMN but had a minor influence on cell
      migration and peripheral analgesia, probably because of the low expression of
      chemokines in the inflamed paw and one of the decreased beta-endorphin content in
      PMN.

PMID- 14695737
TI  - Diplopia: a complication of dural puncture.

PMID- 14695738
TI  - Approach to painful disorders by Serefeddin Sabuncuoglu in the fifteenth century
      Ottoman period.

PMID- 14695739
TI  - Perioperative beta-adrenergic receptor blockade: physiologic foundations and
      clinical controversies.

PMID- 14695740
TI  - Concerning neurologic sequelae of spinal anesthesia.

PMID- 14695741
TI  - Low bispectral index values in awake volunteers receiving a combination of
      propofol and midazolam.

PMID- 14695742
TI  - Transient cardiovascular toxicity with unintentional intravascular injection of
      3% 2-chloroprocaine in a 2-month-old infant.

PMID- 14695743
TI  - Anesthesia management of orthotopic liver transplantation in a patient with
      mustard repair of transposition of great arteries and superior vena caval
      obstruction.

PMID- 14695744
TI  - Bulk liquid oxygen supply failure.

PMID- 14695745
TI  - Combined infraclavicular plexus block with suprascapular nerve block for humeral
      head surgery in a patient with respiratory failure: is an alternative approach
      really the best option for the lungs?

PMID- 14695746
TI  - Mechanisms of hypotension and bradycardia during regional anesthesia in the
      sitting position.

PMID- 14695747
TI  - Erythrocyte transfusion and postsurgical morbidity in cardiac surgery patients:
      is it the storage time or the number of transfused concentrates that really
      matters?

PMID- 14695748
TI  - Bispectral index monitoring and fast tracking after ambulatory surgery: an
      unexpected finding?

PMID- 14695749
TI  - Sub-Tenon techniques should be one option among many.

PMID- 14695750
TI  - Topical anesthesia is the technique of choice for routine cataract surgery.

PMID- 14695751
TI  - Combination of morphine with ketamine for patient-controlled analgesia: is
      ketamine plasma concentration adequate?

PMID- 14695753
TI  - Catastrophic failure of Aestiva 3000 absorber manifold.

PMID- 14695752
TI  - Spinal cord temperature.

PMID- 14695754
TI  - Potential eye injury due to protective face shields.

PMID- 14695756
TI  - Cotargeting tumor and stroma in a novel chimeric tumor model involving the growth
      of both human prostate cancer and bone stromal cells.
AB  - Stromal-epithelial interaction contributes to local prostate tumor growth,
      androgen-independent progression and distant metastasis. We have established in
      vitro coculture and in vivo chimeric tumor models to evaluate the roles of
      stromal cells isolated from either osteosarcoma or normal bone, a site where
      prostate cancer cells frequently metastasize, in contributing to the growth and
      survival of human prostate cancer cells. We have evaluated extensively the
      effects of toxic gene therapy using luciferase-tagged chimeric human prostate
      cancer models both in vitro and in vivo. In the in vitro cocultured cell model,
      we assessed cancer cell growth and residual cellular proteins after targeting
      either prostate cancer epithelial cells alone or both prostate cancer and bone
      stromal cells. In the in vivo animal model, we measured tumor volume and serum
      prostate-specific antigen (PSA) in mice bearing chimeric prostate tumors
      comprised of human prostate tumor cells and normal bone stromal cells. Our
      results demonstrated that: (1) The rate of human prostate cancer cell growth in
      vitro is accelerated by coculturing with human and rat osteosarcoma or normal
      mouse bone marrow stromal cell lines. No growth stimulation was noted when
      cocultured with a human prostate epithelial cell line. (2) Disabling the growth
      of normal bone stromal cells using transgenic targeting with a bystander gene,
      herpes simplex virus thymidine kinase (hsv-TK), plus the pro-drug ganciclovir
      (GCV) or acyclovir markedly depressed the growth of cocultured human prostate
      cancer cells in vitro and human prostate cancer-mouse normal bone stroma chimeric
      tumors in vivo. (3) By cotargeting both human prostate cancer and normal mouse
      bone stromal cells in vitro with an adenoviral construct, Ad-hOC-TK (a
      replication-defective Ad5 vector with the bystander transgene hsv-TK under the
      control of a human osteocalcin (hOC) promoter) plus GCV4, we observed greater
      inhibition of tumor cell growth than by targeting a single cell compartment with
      Ad-PSA-TK (a vector construct similar to Ad-hOC-TK except that the transgene
      expression is under regulation by a full-length human PSA promoter). These
      results, taken together, established a basic principle that cotargeting both
      tumor and its supporting stroma is more efficacious than targeting a single cell
      compartment in the treatment of human prostate cancer bone metastasis. This
      principle can be applied to other clinical conditions of cancer growth where
      stroma contribute to the overall growth and survival potential of the cancer.

PMID- 14695757
TI  - A nonviral carrier for targeted gene delivery to tumor cells.
AB  - In this study, we developed a nonviral, cationic, targeted DNA-carrier system by
      coupling SAINT/DOPE lipids to monoclonal antibodies. The two monoclonal
      antibodies used were both tumor specific, that is, MOC31 recognizes the
      epithelial glycoprotein EGP-2 present in carcinomas and Herceptin recognizes the
      HER-2/neu protein in breast and ovarian cancers. Coupling was performed under
      nonreducing conditions by covalent attachment. The coupling procedure appeared to
      be reproducible and the binding capacity of the antibody was not affected by
      linking them to the cationic lipid. Binding and transfection efficiency was
      assayed with target cells and nontarget cells. SAINT/DOPE lipoplexes as such
      appeared to be an effective transfection reagent for various cell lines. After
      coupling SAINT/DOPE to the monoclonal antibodies or F(ab)2 fragments, it was
      shown that the targeted MoAb-SAINT/DOPE lipoplexes preferably bound to target
      cells, compared to binding to the nontarget cells, especially for the Herceptin
      SAINT/DOPE lipoplexes. More importantly, transfection of the target cells could
      also be improved with these targeted lipoplexes. In conclusion, we have shown
      that by using monoclonal antibody-coupled SAINT/DOPE lipoplexes cells targeted
      gene delivery can be achieved, and also a higher number of transfected target
      cells was seen.

PMID- 14695758
TI  - Towards a higher international standard - World Journal of Gastroenterology is to
      be published twice monthly in 2004.

PMID- 14695759
TI  - Primary gastric lymphoma.
AB  - AIM: The purpose of this review is to describe the various aspects of primary
      gastric lymphoma and the treatment options currently available. METHODS: After a
      systematic search of Pubmed, Medscape and MDconsult, we reviewed and retrieved
      literature regarding gastric lymphoma. RESULTS: Primary gastric lymphoma is rare
      however, the incidence of this malignancy is increasing. Chronic gastritis
      secondary to Helicobacter pylori (H pylori) infection has been considered a major
      predisposing factor for MALT lymphoma. Immune histochemical marker studies and
      molecular biology utilizing polymerase chain reaction have facilitated
      appropriate diagnosis and abolished the need for diagnostic surgical resection.
      Advances in imaging techniques including Magnetic Resonance Imaging (MRI) and
      Endoscopic Ultrasonography (EUS) have helped evaluation of tumor extension and
      invasion. The clinical course and prognosis of this disease is dependent on
      histopathological sub-type and stage at the time of diagnosis. Controversy
      remains regarding the best treatment for early stages of this disease.
      Chemotherapy, surgery and combination have been studied and shared almost
      comparable results with survival rate of 70-90%. However, chemotherapy possesses
      the advantage of preserving gastric anatomy. Radiotherapy alone has been tried
      and showed good results. Stage IIIE, IVE disease treatment is solely by
      chemotherapy and surgical resection has been a remote consideration. CONCLUSION:
      We conclude that methods of diagnosis and staging of the primary gastric lymphoma
      have dramatically improved. The modalities of treatment are many and probably
      chemotherapy is superior because of high success rate, preservation of stomach
      and tolerable complications.

PMID- 14695760
TI  - Safety of interferon beta treatment for chronic HCV hepatitis.
AB  - Hepatitis C is a major cause of liver-related morbidity and mortality worldwide.
      In fact, chronic hepatitis C is considered as one of the primary causes of
      chronic liver disease, cirrhosis and hepatocellular carcinoma, and is the most
      common reason for liver transplantation. The primary objectives for the treatment
      of HCV-related chronic hepatitis is to eradicate infection and prevent
      progression of the disease. The treatment has evolved from the use of alpha
      interferon (IFNalpha) alone to the combination of IFNalpha plus ribavirin, with a
      significant improvement in the overall efficacy, and to the newer PEG-IFNs which
      have further increased the virological response, used either alone or in
      combination with ribavirin. Despite these positive results, in terms of efficacy,
      concerns are related to the safety and adverse events. Many patients must reduce
      the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable
      percentage of subjects are not suitable owing to intolerance toward drugs.
      IFNbeta represents a potential therapeutic alternative for the treatment of
      chronic viral hepatitis and in some countries it plays an important role in
      therapeutic protocols. Aim of the present paper was to review available data on
      the safety of IFNbeta treatment in HCV-related chronic hepatitis. The rates of
      treatment discontinuation and/or dose modification due to the appearance of
      severe side effects during IFNbeta are generally low and in several clinical
      studies no requirements for treatment discontinuation and/or dose modifications
      have been reported. The most frequent side effects experienced during IFNbeta
      treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No
      differences in terms of side-effect frequency and severity between responders and
      non-responders have been reported. A more recent study, performed to compare
      IFNbeta alone or in combination with ribavirin, confirmed the good safety profile
      of both treatments. Similar trends of adverse event frequency have been observed
      in subpopulations such as patients with genotype-1b HCV hepatitis unresponsive to
      IFNalpha treatment or with HCV-related cirrhosis and patients with acute viral
      hepatitis. If further studies will confirm the efficacy of combined IFNbeta and
      ribavirin treatment, this regimen could represent a safe and alternative
      therapeutic option in selected patients.

PMID- 14695761
TI  - Differences in proximal (cardia) versus distal (antral) gastric carcinogenesis
      via the retinoblastoma pathway.
AB  - AIM: Disruption of cell cycle regulation is a critical event in carcinogenesis,
      and alteration of the retinoblastoma (pRb) tumour suppressor pathway is frequent.
      The aim of this study was to compare alterations in this pathway in proximal and
      distal gastric carcinogenesis in an effort to explain the observed striking
      epidemiological differences. METHODS: Immunohistochemistry was performed to
      investigate expression of p16 and pRb in the following groups of both proximal
      (cardia) and distal (antral) tissue samples: (a) biopsies showing normal mucosa,
      (b) biopsies showing intestinal metaplasia and, (c) gastric cancer resection
      specimens including uninvolved mucosa and tumour. RESULTS: In the antrum there
      were highly significant trends for increased p16 expression with concomitant (and
      in the group of carcinomas inversely proportional) decreased pRb expression from
      normal mucosa to intestinal metaplasia to uninvolved mucosa (from cancer
      resections) to carcinoma. In the cardia, there were no differences in p16
      expression between the various types of tissue samples whereas pRb expression was
      higher in normal mucosa compared with intestinal metaplasia and tissue from
      cancer resections. CONCLUSION: Alterations in the pRb pathway appear to play a
      more significant role in distal gastric carcinogenesis. It may be an early event
      in the former location since the trend towards p16 overexpression with
      concomitant pRb underexpression was seen as early as between normal mucosa and
      intestinal metaplasia. Importantly, the marked differences in expression of pRb
      and p16 between the cardia and antrum strongly support the hypothesis that
      tumours of the two locations are genetically different which may account for some
      of the observed epidemiological differences.

PMID- 14695762
TI  - Effect of NF-kappaB, survivin, Bcl-2 and Caspase3 on apoptosis of gastric cancer
      cells induced by tumor necrosis factor related apoptosis inducing ligand.
AB  - AIM: To study the effect of NF-kappaB, survivin, Bcl-2 and Caspase3 on tumor
      necrosis factors related apoptosis inducing ligand (TRAIL) induced apoptosis of
      gastric cancer cells. METHODS: Gastric cancer cells of SGC-7901, MKN28, MKN45 and
      AGS lines were cultured in PRMI-1640 medium and the apoptosis rates of the cells
      of 4 lines were observed after treatment of tumor necrosis factors related
      apoptosis inducing ligand (TRAIL) with a flow cytometer. The expression of NF
      kappaB, survivin, Bcl-2 and Caspase3 in gastric cancer cells of 4 lines was
      analyzed with Western blot. RESULTS: After the gastric cancer cells were exposed
      to TRAIL 300 ng/ml for 24 hours, the apoptosis rate was 36.05%, 20.27%, 16.50%
      and 11.80% in MKN28, MKN45, AGS and SGC-7901cells respectively. Western blot
      revealed that the expressions of NF-kappaB and survivin were lower in MKN28 cells
      than in MKN45, AGS and SGC-7901 cells. In contrast, the expression of Caspase3
      was higher in MKN28 cells than in MKN45, AGS and SGC-7901 cells. CONCLUSION:
      There is a selectivity of TRAIL potency to induce apoptosis in gastric cancer
      cells of different cell lines. The anticancer potency of TRAIL is associated with
      the decreased expression of NF-kappaB and survivin and increased expression of
      Caspase3 of gastric cancer cells.

PMID- 14695763
TI  - Construction and identification of recombinant vectors carrying herpes simplex
      virus thymidine kinase and cytokine genes expressed in gastric carcinoma cell
      line SGC7901.
AB  - AIM: To construct and identify the recombinant vectors carrying herpes simplex
      virus thymidine kinase (HSV-TK) and tumor necrosis factor alpha (TNF-alpha) or
      interleukin-2 (IL-2) genes expressed in gastric carcinoma cell line SGC7901.
      METHODS: The fragments of HSV-TK, internal ribosome entry sites (IRES) and TNF
      alpha or IL-2 genes were inserted in a TK-IRES-TNF-alpha or TK-IRES-IL-2 order
      into pEGFP-N(3) and pLXSN to generate the therapeutic vectors pEGFP-TT, pEGFP-TI,
      pL(TT)SN and pL(TI)SN respectively, which were structurally confirmed by the
      digestion analysis of restriction endonuclease. The former two plasmids were used
      for the transient expression of recombinant proteins in the target cells while
      pL(TT)SN and pL(TI)SN were transfected into SGC7901 cells by lipofectamine for
      the stable expression of objective genes through G418 selection. The protein
      products expressed transiently and stably in SGC7901 cells by the constructed
      vectors were confirmed by fluorescent microscopy and Western blot respectively.
      RESULTS: The inserted fragments in all constructed plasmids were structurally
      confirmed to be consistent with that of the published data. In the transient
      expression, both pEGFP-TT and pEGFP-TI were shown expressed in nearly 50% of the
      transfected SGC7901 cells. Similarly, the G418 selected vectors PL(TT)SN and
      PL(TI)SN were confirmed to be successful in the stable expression of the
      objective proteins in the target cells. CONCLUSION: The constructed recombinant
      vectors in the present study that can express the suicide gene TK in combination
      with cytokines genes may serve as the potential tools to perform more effective
      investigations in future for the gene therapy of gastric carcinoma.

PMID- 14695764
TI  - Does surgical resection of hepatocellular carcinoma accelerate cancer
      dissemination?
AB  - AIM: This study was to investigate whether surgery could increase cancer
      dissemination and postoperative recurrence in patients with hepatocellular
      carcinoma (HCC) by detection of human alpha-fetoprotein messenger RNA (hAFP
      mRNA). hAFP mRNA in the peripheral blood of patients with HCC has been considered
      as a surrogate marker for circulating tumor cells. METHODS: Eighty-one
      consecutive patients who underwent curative resection for HCC entered this
      prospective cohort study. We examined hAFP mRNA from the peripheral blood
      obtained preoperatively, perioperatively, and postoperatively to correlate the
      prognosis after curative resections from HCC patients and from the control
      subjects. Detection of hAFP mRNA by reverse transcriptase and polymerase chain
      reaction amplification (RT-PCR) was performed with primers specifically. The
      relations between the clinical variables (age, sex, associated liver cirrhosis,
      hepatitis B virus infection, hepatitis C virus infection, serum ?-fetoprotein and
      Child-Pugh class), the histological variables (size, capsule, vascular
      permeation, grade of differentiation, and daughter nodules), hAFP mRNA in
      peripheral blood of 3 different sessions, and postoperative course (recurrence,
      and recurrence related death) were analysed. RESULTS: No hAFP mRNA was detected
      in control group subjects. Twenty-two (27%), 24 (30%) and 19 (23%) of 81 HCC
      patients had hAFP mRNA positivity in the preoperative, perioperative and
      postoperative peripheral blood. The preoperative presence did not influence the
      risk of HCC recurrence (55% vs 41%, P=0.280). In contrast, patients with
      postoperative presence had a significantly higher recurrence (90% vs 31%,
      P<0.001; odds ratio 19.2; 95% confidence interval: 4.0-91.7). In the multivariate
      analysis by COX proportional hazards model, postoperative positivity had a
      significant influence on recurrence (P=0.067) and recurrence related mortality
      (P=0.017). Whereas, the perioperative positivity of hAFP mRNA did not increase
      HCC recurrence (58% vs.39%, P=0.093). The correlation between perioperative hAFP
      mRNA positivity and recurrence related mortality had no statistical significance
      (P=0.836). CONCLUSION: From our study, perioperative detection of hAFP mRNA in
      peripheral blood of patients has no clinical relevance and significant role in
      the prediction of HCC recurrence. Surgical resection itself may not accelerate
      cancer dissemination and does not increase postoperative recurrence significantly
      either.

PMID- 14695765
TI  - Effects of Ginkgo biloba extract on cell proliferation and cytotoxicity in human
      hepatocellular carcinoma cells.
AB  - AIM: To study the effect of Ginkgo biloba extract (EGb 761) containing 22-27%
      flavonoids (ginkgo-flavone glycosides) and 5-7% terpenoids (ginkgolides and
      bilobalides) on cell proliferation and cytotoxicity in human hepatocellular
      carcinoma (HCC) cells. METHODS: Human HCC cell lines (HepG2 and Hep3B) were
      incubated with various concentrations (0-1 000 mg/L) of EGb 761 solution. After
      24 h incubation, cell proliferation and cytotoxicity were determined by 3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
      (MTS) assay and lactate dehydrogenase (LDH) release, respectively. After 48 h
      incubation, the expression of proliferating cell nuclear antigen (PCNA) and p53
      protein was measured by Western blotting. RESULTS: The results showed that EGb
      761 (50-1 000 mg/L) significantly suppressed cell proliferation and increased LDH
      release (P<0.05) in HepG2 and Hep3B cells compared with the control group. The
      cell proliferation of HepG2 and Hep3B cells treated with EGb 761 (1 000 mg/L) was
      45% and 39% of the control group (P<0.05), respectively. LDH release of HepG2
      cells without and with EGb 761 (1 000 mg/L) treatment was 6.7% and 37.7%,
      respectively, and that of Hep3B cells without and with EGb 761 (1 000 mg/L)
      treatment was 7.2% and 40.3%, respectively. The expression of PCNA and p53
      protein in HepG2 cells treated with EGb 761 (1 000 mg/L) was 85% and 174% of the
      control group, respectively. CONCLUSION: Ginkgo biloba extract significantly can
      suppress proliferation and increase cytotoxicity in HepG2 and Hep3B cells.
      Additionally, Ginkgo biloba extract can decrease PCNA and increase p53 expression
      in HepG2 cells.

PMID- 14695766
TI  - Increased nociceptin/orphanin FQ plasma levels in hepatocellular carcinoma.
AB  - AIM: The heptadecapeptide nociceptin alias orphanin FQ is the endogenous agonist
      of opioid receptor-like1 receptor. It is involved in modulation of pain and
      cognition. High blood level was reported in patients with acute and chronic pain,
      and in Wilson disease. An accidental observation led us to investigate nociceptin
      in hepatocellular carcinoma. METHODS: Plasma nociceptin level was measured by
      radioimmunoassay, aprotinin was used as protease inhibitor. Hepatocellular
      carcinoma was diagnosed by laboratory, ultrasound, other imaging, and confirmed
      by fine needle biopsy. Results were compared to healthy controls and patients
      with other chronic liver diseases. RESULTS: Although nociceptin levels were
      elevated in patients with Wilson disease (14.0+/-2.7 pg/mL, n=26), primary
      biliary cirrhosis (12.1+/-3.2 pg/mL, n=21) and liver cirrhosis (12.8+/-4.0 pg/mL,
      n=15) compared to the healthy controls (9.2+/-1.8 pg/mL, n=29, P<0.001 for each),
      in patients with hepatocellular carcinoma a ten-fold increase was found (105.9+/
      14.4 pg/mL, n=29, P<0.0001). High plasma levels were found in each hepatocellular
      carcinoma patient including those with normal alpha fetoprotein and those with
      pain (104.9+/-14.9 pg/mL, n=12) and without (107.7+/-14.5 pg/mL, n=6).
      CONCLUSION: A very high nociceptin plasma level seems to be an indicator for
      hepatocellular carcinoma. Further research is needed to clarify the mechanism and
      clinical significance of this novel finding.

PMID- 14695768
TI  - Superantigen-SEA gene modified tumor vaccine for hepatocellular carcinoma: an in
      vitro study.
AB  - AIM: To construct an eukaryotic superantigen gene expression vector containing
      the recombinant gene of SEA and CD80 molecule transmembrane region (CD80TM), and
      to express staphylococcus enterotoxin A (SEA) on the membrane of hepatocellular
      carcinoma (HCC) cell to form a superantigen gene modified tumor vaccine for HCC.
      METHODS: SEA and linker-CD80TM gene were amplified through PCR from plasmid
      containing cDNA of SEA and CD80. Gene fragments were then subcloned into the
      multiple cloning sites of retroviral vector pLXSN. Recombinant plasmid was
      transferred into HepG2 cells mediated with lipofectamine, positive clones were
      selected in culture medium containing G418. RT-PCR and indirect
      immunofluorescence studies confirmed that SEA was expressed specifically on HCC
      cell membrane. INFgamma-ELISPOT study demonstrated that SEA protein was expressed
      on the membrane of HCC cells. Cytotoxicity of HepG2-SEA primed CTLs (SEA-T) was
      analyzed by (51)Cr release assay. T cells cultured with rhIL-2 (IL-2-T) were used
      as control. RESULTS: Restriction digestion and sequence analyses confirmed the
      correctness of length, position and orientation of inserted fusion genes. SEA was
      expressed on the surface of HepG2 cells, HepG2-SEA had strong stimulating effect
      on production of HepG2 specific CTL (P<0.001). SEA-T had enhanced cytotoxicity to
      HepG2 cells (P<0.05). CONCLUSION: Tumor cell membrane expressed superantigen can
      be used to reinforce the immune effect of tumor cell vaccine for HCC, which
      provides a new method of the enhanced active immunotherapy for HCC.

PMID- 14695767
TI  - Potential role of p53 mutation in chemical hepatocarcinogenesis of rats.
AB  - AIM: Inactivation of p53 gene is one of the most frequent genetic alterations in
      carcinogenesis. The mutation status of p53 gene was analyzed, in order to
      understand the effect of p53 mutation on chemical hepatocarcinogenesis of rats.
      METHODS: During hepatocarcinogenesis of rats induced by 3'-methyl-4-
      dimethylaminoazobenzene (3'-Me-DAB), prehepatocarcinoma and hepatocarcinoma foci
      were collected by laser capture microdissection (LCM), and quantitatively
      analyzed for levels of p53 mRNA by LightCycler(TM) real-time RT-PCR and for
      mutations in p53 gene exons 5-8 by direct sequencing. RESULTS: Samples consisting
      of 44 precancerous foci and 24 cancerous foci were collected by LCM. A
      quantitative analysis of p53 mRNA showed that p53 mRNA peaked at an early stage
      (week 6) in the prehepatocarcinoma lesion, more than ten times that of adjacent
      normal tissue, and gradually decreased from week 6 to week 24. The expression of
      p53 mRNA in adjacent normal tissue was significantly lower than that in
      prehepatocarcinoma. Similar to prehepatocarcinoma, p53 mRNA in cancer was
      markedly higher than that in adjacent normal tissue at week 12, and was closer to
      normal at week 24. Direct p53 gene sequencing showed that 35.3% (24/68) (9
      precancer, 15 cancer) LCM samples exhibited point mutations, 20.5% of
      prehepatocarcinoma LCM samples presented missense mutations at exon 6/7 or/and 8,
      and was markedly lower than 62.5% of hepatocarcinoma ones (P<0.01). Mutation of
      p53 gene formed the mutant hot spots at 5 codons. Positive immunostaining for p53
      protein could be seen in prehepatocarcinoma and hepatocarcinoma foci at 24 weeks.
      CONCLUSION: p53 gene mutation is present in initial chemical
      hepatocarcinogenesis, and the mutation of p53 gene induced by 3'-Me-DAB is an
      important factor of hepatocarcinogenesis.

PMID- 14695769
TI  - CT-guided percutaneous ethanol injection with disposable curved needle for
      treatment of malignant liver neoplasms and their metastases in retroperitoneal
      lymph nodes.
AB  - AIM: To explore the feasibility of computed tomography (CT)-guided percutaneous
      ethanol injection (PEI) using a disposable curved needle for treatment of
      malignant liver neoplasms and their metastases in retroperitoneal lymph nodes.
      METHODS: CT-guided PEI was conducted using a disposable curved needle in 26
      malignant liver tumors smaller than 5 cm in diameter and 5 lymph node metastases
      of liver cancer in the retroperitoneal space. The disposable curved needle was
      composed of a straight trocar (21G) and stylet, a disposable curved tip (25 G)
      and a fine stylet. For the tumors found in deep sites and difficult to reach, or
      for hepatic masses inaccessible to the injection using a straight needle because
      of portal vein and bile ducts, the straight trocar was used at first to reach the
      side of the tumor. Then, the disposable curved needle was used via the trocar.
      When the needle reached the tumor center, appropriate amount of ethanol was
      injected. For relatively large malignant liver tumors, multi-point injection was
      carried out for a better distribution of the ethanol injected throughout the
      masses. The curved needle was also used for treatment of the metastasis in
      retroperitoneal lymph nodes blocked by blood vessels and inaccessible by the
      straight needle. RESULTS: All of the 26 liver tumors received 2 or more times of
      successful PEI, through which ethanol was distributed throughout the whole tumor
      mass. Effect of the treatment was monitored by contrast-enhanced multi-phase CT
      and magnetic resonance imaging (MRI) examinations three months later. Of the 18
      lesions whose diameters were smaller than 3 cm, the necrotic change across the
      whole mass and that in most areas were observed in 15 and 3 tumors, respectively.
      Among the 8 tumors sizing up to 5 cm, 5 were completely necrotic and 3 largely
      necrotic. Levels of tumor seromarkers were significantly reduced in some of the
      cases. In 5 patients with metastases of liver cancer in retroperitoneal lymph
      nodes who received 1 to 3 times of PEI, all the foci treated were completely
      necrotic and smaller demonstrated by dynamic contrast-enhanced CT or MRI 3 months
      later. CONCLUSION: CT-guided PEI using a disposable curved needle is effective,
      time-saving and convenient, providing an alternative therapy for the treatment of
      malignant liver tumors and their retroperitoneal lymph node metastases.

PMID- 14695770
TI  - Cooperative inhibitory effects of antisense oligonucleotide of cell adhesion
      molecules and cimetidine on cancer cell adhesion.
AB  - AIM: To explore the cooperative effects of antisense oligonucleotide (ASON) of
      cell adhesion molecules and cimetidine on the expression of E-selectin and ICAM-1
      in endothelial cells and their adhesion to tumor cells. METHODS: After treatment
      of endothelial cells with ASON and/or cimetidine and induction with TNF-alpha,
      the protein and mRNA changes of E-selectin and ICAM-1 in endothelial cells were
      examined by flow cytometry and RT-PCR, respectively. The adhesion rates of
      endothelial cells to tumor cells were measured by cell adhesion experiment.
      RESULTS: In comparison with TNF-alpha inducing group, lipo-ASON and lipo
      ASON/cimetidine could significantly decrease the protein and mRNA levels of E
      selectin and ICAM-1 in endothelial cells, and lipo-ASON/cimetidine had most
      significant inhibitory effect on E-selectin expression (from 36.37+/-1.56% to
      14.23+/-1.07%, P<0.001). Meanwhile, cimetidine alone could inhibit the expression
      of E-selectin(36.37+/-1.56% vs 27.2+/-1.31%, P<0.001), but not ICAM-1 (69.34+/
      2.50% vs 68.07+/-2.10%,P>0.05) and the two kinds of mRNA, either. Compared with
      TNF-alpha inducing group, the rate of adhesion was markedly decreased in lipo-E
      selectin ASON and lipo-E-selectin ASON/cimetidine treated groups(P<0.05), and
      lipo-E-selectin ASON/cimetidine worked better than lipo-E-selectin ASON alone
      except for HepG2/ECV304 group (P<0.05). However, the decrease of adhesion was not
      significant in lipo-ICAM-1 ASON and lipo-ICAM-1 ASON/cimetidine treated groups
      except for HepG2/ECV304 group (P>0.05). CONCLUSION: These data demonstrate that
      ASON in combination with cimetidine in vitro can significantly reduce the
      adhesion between endothelial cells and hepatic or colorectal cancer cells, which
      is stronger than ASON or cimetidine alone. This study provides some useful proofs
      for gene therapy of antiadhesion.

PMID- 14695771
TI  - Single-level dynamic spiral CT of hepatocellular carcinoma: correlation between
      imaging features and density of tumor microvessels.
AB  - AIM: To investigate the correlation of enhancement features of hepatocellular
      carcinoma (HCC) revealed by single-level dynamic spiral CT scanning (DSCT) with
      tumor microvessel density (MVD), and to determine the validity of DSCT in
      assessing in vivo tumor angiogenic activity of HCC. METHODS: Twenty six HCC
      patients were diagnosed histopathologically. DSCT was performed for all patients
      according to standard scanning protocol. Time-density curves were generated,
      relevant curve parameters were measured, and gross enhancement morphology was
      analyzed. Operation was performed to remove HCC lesions 1 to 2 weeks following CT
      scan. Histopathological slides were carefully prepared for the standard F(8)RA
      immunohistochemical staining and tumor microvessel counting. Enhancement imaging
      features of HCC lesions were correlatively studied with tumor MVD and its intra
      tumor distribution characteristics. RESULTS: On DSCT images of HCC lesions, three
      patterns of time-density curve and three types of gross enhancement morphology
      were recognized. Histomorphologically, the distribution of positively stained
      tumor endothelial cells within tumor was categorized into 3 types. Curve
      parameters such as peak enhancement value and contrast enhancement ratio were
      significantly correlated with tumor tissue MVD (r=0.508 and r=0.423, P<0.01 and
      P<0.05 respectively). Both the pattern of time-density curve and the gross
      enhancement morphology of HCC lesions were also correlated with tumor MVD, and
      reflected the distributive features of tumor microvessels within HCC lesions.
      Correlation between the likelihood of intrahepatic metastasis of HCC lesions with
      densely enhanced pseudocapsules and rich pseudocapsular tumor MVD was found.
      CONCLUSION: Enhancement imaging features of HCC lesions on DSCT scanning are
      correlated with tumor MVD, and reflect the intra-tumor distribution
      characteristics of tumor microvessels. DSCT is valuable in assessing the
      angiogenic activity and tumor neovascularity of HCC patients in vivo.

PMID- 14695772
TI  - Protective effect of nitric oxide induced by ischemic preconditioning on
      reperfusion injury of rat liver graft.
AB  - AIM: Ischemic preconditioning (IP) is a brief ischemic episode, which confers a
      state of protection against the subsequent long-term ischemia-reperfusion
      injuries. However, little is known regarding the use of IP before the sustained
      cold storage and liver transplantation. The present study was designed to
      evaluate the protective effect of IP on the long-term preservation of liver graft
      and the prolonged anhepatic-phase injury. METHODS: Male Sprague-Dawley rats were
      used as donors and recipients of orthotopic liver transplantation. All livers
      underwent 10 min of ischemia followed by 10 min of reperfusion before harvest.
      Rat liver transplantation was performed with the portal vein clamped for 25 min.
      Tolerance of transplanted liver to the reperfusion injury and liver damage were
      investigated. The changes in adenosine concentration in hepatic tissue and those
      of nitric oxide (NO) and tumor necrosis factor (TNF) in serum were also assessed.
      RESULTS: Recipients with IP significantly improved their one-week survival rate
      and liver function, they had increased levels of circulating NO and hepatic
      adenosine, and a reduced level of serum TNF, as compared to controls.
      Histological changes indicating hepatic injuries appeared improved in the IP
      group compared with those in control group. The protective effect of IP was also
      obtained by administration of adenosine, while blockage of the NO pathway using
      Nomega-nitro-L-arginine methyl ester abolished the protective effect of IP.
      CONCLUSION: IP appears to have a protective effect on the long-term preservation
      of liver graft and the prolonged anhepatic-phase injuries. NO may be involved in
      this process.

PMID- 14695773
TI  - Effects of cytokines on carbon tetrachloride-induced hepatic fibrogenesis in
      rats.
AB  - AIM: To observe the possible effects of transforming growth factor (TGF) beta(1),
      interleukin (IL)-6, tumor-necrosis factor (TNF) alpha and IL-10 on experimental
      rat hepatic fibrosis. METHODS: One hundred SD rats were divided randomly into the
      three groups. Control group received intraperitoneal injection of saline (2
      ml/kg(-1)), twice a week. Fibrogenesis group was injected intraperitoneally with
      50% carbon tetrachloride (CCl(4)) (2 ml/kg(-1)) twice a week. Fibrosis
      intervention group was given IL-10 at a dose of 4 microg/kg(-1) 20 minutes before
      CCl(4) administration from the third week. At the fifth, seventh, and ninth
      weeks, 7 to 10 rats in each group were sacrificed to collect serum. Levels of TGF
      beta(1), TNF-alpha, IL-6 and IL-10 were determined by enzyme-linked immunosorbent
      assay (ELISA). The liver tissues were taken for routine histological examination.
      RESULTS: Hepatic fibrosis was developed with the injection of CCl(4). Values of
      the circulating TGFbeta(1), TNFalpha, IL-6 and IL-10 in the control group were
      25.49+/-5.56 ng/L(-1), 15.18+/-3.83 ng/L(-1), 63.64+/-13.03 ng/L(-1) and 132.90+/
      12.13 ng/L(-1), respectively. Their levels in the CCl(4)-intoxication group were
      31.13+/-6.41 ng/L(-1), 18.91+/-5.31 ng/L(-1), 89.08+/-25.39 ng/L(-1) and 57.63+/
      18.88 ng/L(-1), respectively, and those in the IL-10-intervention group were
      26.11+/-5.32 ng/L(-1), 13.99+/-1.86 ng/L(-1), 74.71+/-21.15 ng/L(-1) and 88.19+/
      20.81 ng/L(-1), respectively. A gradual increase was observed in the levels of
      TGFbeta(1), TNFalpha and IL-6 during hepatic fibrogenesis. These changes were
      partially reversed by simultaneous administration of IL-10. The histological
      parameters, characterized by CCl(4)-intoxification, also seemed to be improved
      with IL-10 treatment, the collagen production was reduced at the ninth week and
      the histological activity index was decreased from 7.9+/-1.2 to 4.7+/-0.9.
      CONCLUSION: TGFbeta(1), TNFalpha and IL-6 may play important roles during CCl(4)
      induced hepatic fibrogenesis, and IL-10 may counterbalance their effects.

PMID- 14695774
TI  - HBV cccDNA in patients' sera as an indicator for HBV reactivation and an early
      signal of liver damage.
AB  - AIM: To evaluate the covalently closed circle DNA (cccDNA) level of hepatitis B
      virus (HBV) in patients' liver and sera. METHODS: HBV DNA was isolated from
      patients' liver biopsies and sera. A sensitive real-time PCR method, which is
      capable of differentiation of HBV viral genomic DNA and cccDNA, was used to
      quantify the total HBV cccDNA. The total HBV viral DNA was quantitated by real
      time PCR using a HBV diagnostic kit (PG Biotech, LTD, Shenzhen, China) described
      previously. RESULTS: For the first time, we measured the level of HBV DNA and
      cccDNA isolated from ten HBV patients' liver biopsies and sera. In the liver
      biopsies, cccDNA was detected from all the biopsy samples. The copy number of
      cccDNA ranged from from 0.03 to 173.1 per cell, the copy number of total HBV DNA
      ranged from 0.08 to 3 717 per cell. The ratio of total HBV DNA to cccDNA ranged
      from 1 to 3 406. In the sera, cccDNA was only detected from six samples whereas
      HBV viral DNA was detected from all ten samples. The ratio of cccDNA to total HBV
      DNA ranged from 0 to 1.77%. To further investigate the reason why cccDNA could
      only be detected in some patients' sera, we performed longitudinal studies. The
      cccDNA was detected from the patients' sera with HBV reactivation but not from
      the patients' sera without HBV reactivation. The level of cccDNA in the sera was
      correlated with ALT and viral load in the HBV reactivation patients. CONCLUSION:
      HBV cccDNA is actively transcribed and replicated in some patients' hepatocytes,
      which is reflected by a high ratio of HBV total DNA vs cccDNA. Detection of
      cccDNA in the liver biopsy will provide an end-point for the anti-HBV therapy.
      The occurrence of cccDNA in the sera is an early signal of liver damage, which
      may be another important clinical parameter.

PMID- 14695775
TI  - Expression of TIMP-1 and TIMP-2 in rats with hepatic fibrosis.
AB  - AIM: To investigate the location and expression of TIMP-1 and TIMP-2 in the liver
      of normal and experimental hepatic fibrosis in rats. METHODS: The rat models of
      experimental immunity hepatic fibrosis (n=20) were prepared by the means of
      immunologic attacking with human serum albumin (HSA), and normal rats (n=10)
      served as control group. Both immunohistochemistry and in situ hybridization
      methods were respectively used to detect the TIMP-1 and TIMP-2 mRNA and related
      antigens in liver. The liver tissue was detected to find out the gene expression
      of TIMP-1 and TIMP-2 with RT-PCR. RESULTS: The TIMP-1 and TIMP-2 related antigens
      in livers of experimental group were expressed in myofibroblasts and fibroblasts
      (TIMP-1: 482+/-65 vs 60+/-20; TIMP-2: 336+/-48 vs 50+/-19, P<0.001). This was the
      most obvious in portal area and fibrous septum. The positive signals were located
      in cytoplasm, not in nucleus. Such distribution and location were confirmed by
      situ hybridization (TIMP-1/beta-actin: 1.86+/-0.47 vs 0.36+/-0.08; TIMP-2/beta
      actin: 1.06+/-0.22 vs 0.36+/-0.08, P<0.001). The expression of TIMP-1 and TIMP-2
      was seen in the liver of normal rats, but the expression level was very low.
      However, the expression of TIMP-1 and TIMP-2 in the liver of experimental group
      was obviously high. CONCLUSION: In the process of hepatic fibrosis, fibroblasts
      and myofibroblasts are the major cells that express TIMPs. The more serious the
      hepatic fibrosis is in the injured liver, the higher the level of TIMP-1 and TIMP
      2 gene expression.

PMID- 14695776
TI  - Protective role of metallothionein (I/II) against pathological damage and
      apoptosis induced by dimethylarsinic acid.
AB  - AIM: To better clarify the main target organs of dimethylarsinic acid toxicity
      and the role of metallothionein (MTs) in modifying dimethylarsinic acid (DMAA)
      toxicity. METHODS: MT-I/II null (MT(-/-)) mice and the corresponding wild-type
      mice (MT(+/+)), six in each group, were exposed to DMAA (0-750 mg/kg body weight)
      by a single oral injection. Twenty four hours later, the lungs, livers and
      kidneys were collected and undergone pathological analysis, induction of
      apoptotic cells as determined by TUNEL and MT concentration was detected by radio
      immunoassay. RESULTS: Remarkable pathological lesions were observed at the doses
      ranging from 350 to 750 mg/kg body weight in the lungs, livers and kidneys and
      MT(+/+) mice exhibited a relatively slight destruction when compared with that in
      dose matched MT(-/-) mice. The number of apoptotic cells was increased in a dose
      dependent manner in the lungs and livers in both types of mice. DMAA produced
      more necrotic cells rather than apoptotic cells at the highest dose of 750 mg/kg,
      however, no significant increase was observed in the kidney. Hepatic MT level in
      MT(+/+) mice was significantly increased by DMAA in a dose-dependent manner and
      there was no detectable amount of hepatic MT in untreated MT(-/-) mice.
      CONCLUSION: DMAA treatment can lead to the induction of apoptosis and
      pathological damage in both types of mice. MT exhibits a protective effect
      against DMAA toxicity.

PMID- 14695777
TI  - Electrophysiological effects of anthopleurin-Q on rat hepatocytes.
AB  - AIM: To study the effects of AP-Q on CCl(4)-induced acute liver injury, delayed
      outward potassium current (I(K)), inward rectifier potassium current (I(K1)) and
      calcium release-activated calcium current (I(CRAC)) in isolated rat hepatocytes.
      METHODS: A single dose of CCl(4) (10 microg/mL, ip) was injected to induce acute
      liver injury in rats. Serum aminotransferase activities were determined. Whole
      cell patch-clamp techniques were used to investigate the effects of AP-Q on
      delayed outward potassium current (I(K)), inward rectifier potassium current
      (I(K1)) and calcium release-activated calcium current (I(CRAC)). RESULTS: AP-Q
      (3.5 and 7 microg/kg) pretreatment significantly reduced ALT and AST activities.
      AP-Q 0.1-100 nM produced a concentration-dependent increase of I(K) with EC(50)
      value of 5.55+/-1.8 nM (n=6). AP-Q 30 nM shifted the I-V curve of I(K) leftward
      and upward. CCl(4) 4 mM decreased I(K) current 28.6+/-6.5% at 140 mV. After
      exposure to CCl(4) for 5 min, AP-Q 30 nM attenuated the decrease of I(K) induced
      by CCl(4) close to normal amplitude. AP-Q 0.01-100 nM had no significant effect
      on either inward or outward components of I(K1) at any membrane potential
      examined. AP-Q 0.1-100 nM had no significant influence on the peak amplitude of
      I(CRAC), either, and did not affect the shape of its current voltage curve.
      CONCLUSION: AP-Q has a protective effect on CCl(4)-induced liver injury, probably
      through selectively increased I(K) in hepatocytes.

PMID- 14695778
TI  - Effect of Qingyitang on activity of intracellular Ca2+-Mg2+-ATPase in rats with
      acute pancreatitis.
AB  - AIM: To study the change of intracellular calcium-magnesium ATPase (Ca(2+)-Mg(2+)
      ATPase) activity in pancreas, liver and kidney tissues of rats with acute
      pancreatitis (AP), and to investigate the effects of Qingyitang (QYT) (Decoction
      for clearing the pancreas) and tetrandrine (Tet) and vitamin E (VitE) on the
      activity of Ca(2+)-Mg(2+)-ATPase. METHODS: One hundred and five Sprague-Dawley
      rats were randomly divided into: normal control group, AP group, treatment group
      with QYT (1 ml/100 g) or Tet (0.4 ml/100 g) or VitE (100 mg/kg). AP model was
      prepared by a retrograde injection of sodium taurocholate into the pancreatic
      duct. Tissues of pancreas, liver and kidney of the animals were taken at 1 h, 5
      h, 10 h respectively after AP induction, and the activity of Ca(2+)-Mg(2+)-ATPase
      was studied using enzyme-histochemistry staining. Meanwhile, the expression of
      Ca(2+)-Mg(2+)-ATPase of the tissues was studied by RT-PCR. RESULTS: The results
      showed that the positive rate of Ca(2+)-Mg(2+)-ATPase in AP group (8.3%, 25%,
      29.2%) was lower than that in normal control group (100%) in all tissues
      (P<0.01), the positive rate of Ca(2+)-Mg(2+)-ATPase in treatment group with QYT
      (58.3%, 83.3%, 83.3%), Tet (50.0%, 70.8%, 75.0%) and VitE (54.2%, 75.0%, 79.2%)
      was higher than that in AP group (8.3%, 25.0%, 29.2%) in all tissues (P<0.01). RT
      PCR results demonstrated that in treatment groups Ca(2+)-Mg(2+)-ATPase gene
      expression in pancreas tissue was higher than that in AP group at the observing
      time points, and the expression at 5 h was higher than that at 1 h. The
      expression of Ca(2+)-Mg(2+)-ATPase in liver tissue was positive, but without
      significant difference between different groups. CONCLUSION: The activity and
      expression of intracellular Ca(2+)-Mg(2+)-ATPase decreased in rats with AP,
      suggesting that Ca(2+)-Mg(2+)-ATPase may contribute to the occurrence and
      development of cellular calcium overload in AP. QYT, Tet and VitE can increase
      the activity and expression of Ca(2+)-Mg(2+)-ATPase and may relieve intracellular
      calcium overload to protect the tissue and cells from injuries.

PMID- 14695779
TI  - Red oil A5 inhibits proliferation and induces apoptosis in pancreatic cancer
      cells.
AB  - AIM: To study the effect of red oil A5 on pancreatic cancer cells and its
      possible mechanisms. METHODS: Effect of different concentrations of red oil A5 on
      proliferation of three pancreatic cancer cell lines, AsPC-1, MiaPaCa-2 and S2013,
      was measured by (3)H-methyl thymidine incorporation. Time-dependent effects of
      1:32 000 red oil A5 on proliferation of three pancreatic cancer cell lines, were
      also measured by (3)H-methyl thymidine incorporation, and Time-course effects of
      1:32 000 red oil A5 on cell number. The cells were counted by Z1-Coulter Counter.
      Flow-cytometric analysis of cellular DNA content in the control and red oil A5
      treated AsPC-1, MiaPaCa-2 and S2013 cells, were stained with propidium iodide.
      TUNEL assay of red oil A5-induced pancreatic cancer cell apoptosis was performed.
      Western blotting of the cytochrome c protein in AsPC-1, MiaPaCa-2 and S2013 cells
      treated 24 hours with 1:32 000 red oil A5 was performed. Proteins in cytosolic
      fraction and in mitochondria fraction were extracted. Proteins extracted from
      each sample were electrophoresed on SDS-PAGE gels and then were transferred to
      nitrocellulose membranes. Cytochrome c was identified using a monoclonal
      cytochrome c antibody. Western blotting of the caspase-3 protein in AsPC-1,
      MiaPaCa-2 and S2013 cells treated with 1:32 000 red oil A5 for 24 hours was
      carried out. Proteins in whole cellular lysates were electrophoresed on SDS-PAGE
      gels and then transferred to nitrocellulose membranes. Caspase-3 was identified
      using a specific antibody. Western blotting of poly-ADP ribose polymerase (PARP)
      protein in AsPC-1, MiaPaCa-2 and S2013 cells treated with 1:32 000 red oil A5 for
      24 hours was performed. Proteins in whole cellular lysates were separated by
      electrophoresis on SDS-PAGE gels and then transferred to nitrocellulose
      membranes. PARP was identified by using a monoclonal antibody. RESULTS: Red oil
      A5 caused dose- and time-dependent inhibition of pancreatic cancer cell
      proliferation. Propidium iodide DNA staining showed an increase of the sub-G0/G1
      cell population. The DNA fragmentation induced by red oil A5 in these three cell
      lines was confirmed by the TUNEL assay. Furthermore, Western blotting analysis
      indicated that cytochrome c was released from mitochondria to cytosol during
      apoptosis, and caspase-3 was activated following red oil A5 treatment which was
      measured by procaspase-3 cleavage and PARP cleavage. CONCLUSION: These findings
      show that red oil A5 has potent anti-proliferative effects on human pancreatic
      cancer cells with induction of apoptosis in vitro.

PMID- 14695780
TI  - Transfection of mEpo gene to intestinal epithelium in vivo mediated by oral
      delivery of chitosan-DNA nanoparticles.
AB  - AIM: To prepare the chitosan-pmEpo nanoparticles and to study their ability for
      transcellular and paracellular transport across intestinal epithelia by oral
      administration. METHODS: ICR mice were fed with recombinant plasmid AAV-tetO-CMV
      mEpo (containing mEpo gene) or pCMVbeta(containing LacZ gene), whether it was
      wrapped by chitosan or no. Its size and shape were observed by transmission
      electron microscopy. Agarose gel electrophoresis was used to assess the
      efficiency of encapsulation and stability against nuclease digestion. Before and
      after oral treatmant, blood samples were collected by retro-orbital puncture, and
      hematocrits were used to show the physiological effect of mEpo. RESULTS: Chitosan
      was able to successfully wrap the plasmid and to protect it from DNase
      degradation. Transmission electron microscopy showed that freshly prepared
      particles were approximately 70-150 nm in size and fairly spherical. Three days
      after fed the chitosan-pCMVbeta complex was fed, the mice were killed and most of
      the stomach and 30% of the small intestine were stained. Hematocrit was not
      modified in naive and 'naked' mEpo-fed mice, a rapid increase of hematocrit was
      observed during the first 4 days of treatment in chitosan-mEpo-fed animals,
      reaching 60.9+/-1.2% (P<0.01), and sustained for a week. The second feed (6 days
      after the first feed) was still able to promote a second hematocrit increase in
      chitosan-mEpo-fed animals, reaching 65.9+/-1.4% (P<0.01), while the second
      hematocrit increase did not appear in the 'naked' mEpo-second-fed mice.
      CONCLUSION: Oral chitosan-DNA nanoparticles can efficiently deliver genes to
      enterocytes, and may be used as a useful tool for gene transfer.

PMID- 14695781
TI  - Ultrastructure of junction areas between neurons and astrocytes in rat supraoptic
      nuclei.
AB  - AIM: To determine the ultrastructure of junction areas between neurons and
      astrocytes of supraoptic nuclei in rats orally administered 30 g/L NaCl solution
      for 5 days. METHODS: The anti-connexin (CX) 43 and anti-CX32 double
      immunoelectromicroscopic labeled method, and anti-Fos or anti-glial fibrillary
      acidic protein (GFAP) immunohistochemistry were used to detect changes in the
      junctional area between neurons and astrocytes in supraoptic nuclei of 5 rats
      after 30 g/L NaCL solution was given for 5days. RESULTS: A heterotypic
      connexin32/connexin43 gap junction (HGJ) between neurons and astrocytes (AS) in
      rat supraoptic nuclei was observed, which was characterized by the thickening and
      dark staining of cytomembranes with a narrow cleft between them. The number of
      HGJs and Fos like immunoreactive (-LI) cells was significantly increased
      following hyperosmotic stimuli, that is, the rats were administered 30 g/L NaCl
      solution orally or 90 g/L NaCl solution intravenously. HGJs could be blocked with
      carbenoxolone (CBX), a gap junction blocker, and the number of Fos-LI neurons was
      significantly decreased compared with that in rats without CBX injection, while
      Fos-LI ASs were not affected. CONCLUSION: HGJ may be a rapid adaptive signal
      structure between neurons and ASs in response to stimulation.

PMID- 14695782
TI  - Effects of exercise on lipid metabolism and musculoskeletal fitness in female
      athletes.
AB  - AIM: This study investigated the effects of intense training on lipid metabolism,
      bone metabolism and bone mineral density (BMD) in female athletes. METHODS: Sixty
      six female subjects participated in this study, age ranging from 18 to 55 years.
      The sample group included thirty-six athletic subjects and the control group
      comprised thirty non-athletic individuals. Five athletes competed with national
      level (5/36) and nine non-athletic subjects (9/30) were postmenopausal women. The
      assessment items included body composition, radius BMD, calcaneus BMD, lung
      function, muscular endurance, renal and liver function, bone marker assay and
      hormone status. All data were analysed, using SPSS 10.0 software, and were
      presented as mean rank statistical difference, using the Kurskal-Wallis (K-W)
      test. After that the non-parameter statistics were used. Either K value or P
      value below 0.05 was considered significant. RESULTS: Urine
      deoxypyridinoline/creatinine (Dpd/Cre) levels increased significantly (5.93+/
      2.31 vs 6.85+/-1.43, K<0.01), sit-reach (29.30+/-9.48 cm vs 41.31+/-9.43 cm,
      K<0.001, P<0.001), 1 minute sit-ups with bended knees (1 min sit-ups) (17.60+/
      9.34 count vs 30.00+/-10.38 count, K<0.001, P<0.001), and vertical jump (25.27+/
      6.63 cm vs 34.69+/-7.99 cm, K<0.001, P<0.001) improved significantly in the
      athletes group. The athletes group also had a significantly increased level of
      estriol (E(3)) (0.14+/-0.13 pg/mL vs 0.07+/-0.04 pg/mL, K<0.01, P<0.01), radius
      BMD (1.37+/-0.49 gm/cm(2) vs 1.19+/-0.40 gm/cm(2), K<0.05) and calcaneus BMD
      (0.57+/-0.17 gm/cm(2) vs -0.20+/-0.17 gm/cm(2), K<0.01, P<0.05) compared with
      those of the controls. The high density lipoprotein (HDL) (65.00+/-14.02 mg/dL vs
      52.26+/-4.84 mg/dL, K<0.05, P<0.05) was significantly lower in postmenopausal
      inactive athletes (5/36) than premenopausal active athletes (31/36). On the other
      hand, low-density lipoprotein (LDL) (98.35+/-23.84 mg/dL vs 131.00+/-21.63 mg/dL,
      K<0.05, P<0.01), cholesterol (CHO) (164.03+/-27.01 mg/dL vs 193.00+/-23.48 mg/dL,
      K<0.05, P<0.05), triglyceride (TG) (63.00+/-26.39 mg/dL vs 147.00+/- 87.21 mg/dL,
      K<0.01), body fat % (BF%) (28.16+/-4.90% vs 34.84+/-4.44%, K<0.05, P<0.001) and
      body mass index (BMI) (21.98+/-2.98 kg/m(2) vs 26.42+/-5.01 kg/m(2), K<0.05,
      P<0.001) were significantly higher in postmenopausal inactive athletes (5/36)
      than premenopausal active athletes (31/36). TG (90.22+/-39.82 mg/dL vs 147.00+/
      87.21 mg/dL), CHO (186.44+/-24.90 mg/dL vs 193.00+/-23.48 mg/dL) were higher, but
      the HDL was significantly lower (62.18+/-10.68 mg/dL vs 52.26+/-4.84 mg/dL,
      P<0.05) in postmenopausal athletes (5/36) group than in postmenopausal control
      group (9/30). CONCLUSION: Postmenopausal athletes (5/36) who no longer took
      competing exercises had reduced levels of physical activity, faced increased risk
      of cardiovascular disease compared to active athletes (31/36) and the
      postmenopausal controls (9/30). We may thus concluded that long term exercise
      effectively improves musculoskeletal fitness and prevents BMD loss in female
      athletes.

PMID- 14695783
TI  - Acute diarrhea during army field exercise in southern China.
AB  - AIM: During emergency period, infectious diseases can be a major threat to
      military forces. During field training in southern China, diarrhea is the main
      cause of nonbattle injury. To evaluate the causes of and risk factors for
      diarrhea in emergency period, we collected clinical and epidemiological data from
      the People's Liberation Army (PLA) during field training in southern China.
      METHODS: From September 25 to October 2 1997, 2636 military personnel were
      investigated. Fecal sample cultures for lapactic pathogens were obtained from 103
      military personnel with diarrhea. In addition, a questionnaire was administered
      to 103 cases and 206 controls to evaluate the association between illness and
      potential risk factors. At the same time, another questionnaire of 1:4 case-case
      control was administered to 22 severe cases (each severe case paired 4 mild
      cases). RESULTS: The training troop's diarrhea incidence rate was significantly
      higher than that of garrison. The diarrhea incidence rate of officers was
      significantly lower than that of soldiers. A lapactic pathogen was identified in
      63.1% (65/103) of the troops with diarrhea. Enterotoxigenic Escherichia coli
      (35.0%) and plesiomona shigelloides (16.5%) were the most common bacterial
      pathogens. All bacterial isolates were sensitive to norfloxacin and ceftazidine.
      However, almost all of them were resistant to sulfamethoxazole, trimethoprim
      sulfamethoxazole, oxytetracycline, doxycycline, furazolidone, ampicillin and
      cloromycetin to a different degree. Risk factors associated with diarrhea
      included drinking raw water, eating outside, contacting diarrhea patients,
      lacking sanitation, depression, lacking sleep, which were established by multiple
      factor logistic regression analysis. In addition, the unit incidence rate was
      associated with the density of flies and the average daily boiled water available
      by regression and discriminate analysis. CONCLUSION: A series of risk factors are
      associated with the incidence rate of diarrhea. Our results may provide a useful
      basis for prevention and cure of diarrhea in emergency period of PLA.

PMID- 14695784
TI  - Alteration of somatostatin receptor subtype 2 gene expression in pancreatic tumor
      angiogenesis.
AB  - AIM: To explore the difference of somatostatin receptor subtype 2 (SST2R) gene
      expression in pancreatic cancerous tissue and its adjacent tissue, and the
      relationship between the change of SST2R gene expression and pancreatic tumor
      angiogenesis related genes. METHODS: The expressions of SST2R, DPC4, p53 and ras
      genes in cancer tissues of 40 patients with primary pancreatic cancer, and the
      expression of SST2R gene in its adjacent tissue were determined by
      immunohistochemiscal LSAB method and EnVision(TM) method. Chi-square test was
      used to analyze the difference in expression of SST2R in pancreatic cancer tissue
      and its adjacent tissue, and the correlation of SST2R gene expression with the
      expression of p53, ras and DPC4 genes. RESULTS: Of the tissue specimens from 40
      patients with primary pancreatic cancer, 35 (87.5%) cancer tissues showed a
      negative expression of SST2R gene, whereas 34 (85%) a positive expression of
      SST2R gene in its adjacent tissues. Five (12.5%) cancer tissues and its adjacent
      tissues simultaneously expressed SST2R. The expression of SST2R gene was markedly
      higher in pancreatic tissues adjacent to cancer than in pancreatic cancer tissues
      (P<0.05). The expression rates of p53, ras and DPC4 genes were 50%, 60% and
      72.5%, respectively. There was a significant negative correlation of SST2R with
      p53 and ras genes (chi(1)(2)=9.33, chi(2)(2)=15.43, P<0.01), but no significant
      correlation with DPC4 gene (chi(2)=2.08, P>0.05). CONCLUSION: There was a
      significant difference of SST2R gene expression in pancreatic cancer tissues and
      its adjacent tissues, which might be one cause for the different therapeutic
      effects of somatostatin and its analogs on pancreatic cancer patients. There were
      abnormal expressions of SST2R, DPC4, p53 and ras genes in pancreatic
      carcinogenesis, and moreover, the loss or decrease of SST2R gene expression was
      significantly negatively correlated with the overexpression of tumor angiogenesis
      correlated p53 and ras genes, suggesting that SST2R gene together with p53 and
      ras genes may participate in pancreatic cancerous angiogenesis.

PMID- 14695785
TI  - Perioperative cimetidine administration promotes peripheral blood lymphocytes and
      tumor infiltrating lymphocytes in patients with gastrointestinal cancer: Results
      of a randomized controlled clinical trial.
AB  - AIM: To study the effects of perioperative administration of cimetidine (CIM) on
      peripheral blood lymphocytes, natural killer (NK) cells and tumor infiltrating
      lymphocytes (TIL) in patients with gastrointestinal (GI) cancer. METHODS: Forty
      nine GI cancer patients were randomized into treatment group, who took CIM in
      perioperative period, and control group, who did not take the drug. The treatment
      was initiated 7 days before operation and continued for 10 days after surgery. At
      baseline examination before operation, on the 2nd and 10th postoperative days,
      total T lymphocytes, T helper cells, T suppressor cells, and NK cells in
      peripheral blood were measured respectively by immunocytochemical method using
      mouse-anti human CD(3), CD(4), CD(8) and CD(57) monoclonal antibodies. Blood
      samples from 20 healthy volunteers were treated in the same way as normal
      controls. Surgical specimens were examined during routine histopathological
      evaluation for the presence of TIL in tumor margin. Immunohistochemical study was
      performed to measure the proportion of T and B lymphocytes in TIL population. T
      and B lymphocytes were detected respectively using mouse-anti-human CD(3) and
      CD(20) monoclonal antibodies. RESULTS: In comparison with normal controls, both
      the treatment and control groups had decreased T cells, T helper cells and NK
      cells at baseline. In control group, total T cells, T helper cells and NK cells
      declined continuously with the disease progression and the decrease became more
      obvious after operation. From baseline to the 2nd postoperative day, the
      proportion of total T cells, T helper cells, and NK cells went down from 60.5+/
      4.6% to 56.2+/-3.8%, 33.4+/-3.7% to 28.1+/-3.4%, and 15.0+/-2.8% to 14.2+/-2.2%,
      respectively. On the other hand, there were significant improvements in these
      parameters after CIM treatment. On the 10th postoperative day, the treatment
      group had significantly higher percentages of total T cells, T helper cells and
      NK cells than control group. Moreover, CIM treatment also boosted TIL response,
      as was reflected by findings that 68% (17/25) of the patients in treatment group
      had significant TIL responses and only 25% (6/24) of the cases had discernible
      TIL responses (P<0.01). CONCLUSION: Perioperative application of CIM to GI cancer
      patients could help restore the diminished cellular immunity induced by tumor
      burden and surgical maneuver. The drug could also boost TIL responses to tumor.
      These effects suggest that the drug be used as an immunomodulator for GI cancer
      patients.

PMID- 14695786
TI  - Response of TT virus to IFN plus ribavirin treatment in patients with chronic
      hepatitis C.
AB  - AIM: TT virus (TTV) is a newly described DNA virus related to postransfusion
      hepatitis that produces persistent viremia in the absence of clinical
      manifestations. PEG-IFN plus ribavirin have been useful in the treatment of
      chronic hepatitis C infection. This study investigated the responses of TT virus
      (TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirin therapy. METHODS:
      Fifteen patients infected with HCV were treated with PEG-IFN(0.5 microg/body
      weight/week) and ribavirin (1 000 mg-1 200 mg/daily) for 48 weeks. Blood samples
      were drawn at the beginning and the end of the therapy. Serum TTV DNA and HCV RNA
      were quantified by real time PCR. RESULTS: At the beginning of treatment, TTV
      infection was detected in 10/15 (66.6%) of HCV-infected patients. Loss of serum
      TTV DNA at the end of therapy occurred in 6/10 (60%) patients. Out of these 6
      patients, 4 (67%) became positive for TTV DNA after 6 months of therapy.
      Regarding HCV viremia, 11/15 (73%) patients were negative for serum HCV RNA after
      48 weeks of therapy, 7/11 (64%) of these cases also became negative for TTV DNA
      following the combined treatment. In the 3/4 (75%) patients who were positive for
      HCV RNA at the end of therapy, TTV DNA was detected as well. Sustained HCV
      response at 6 months after treatment was 53% (8/15). CONCLUSION: No TTV sustained
      response can be achieved in any patient after PEG-IFN plus ribavirin
      administration.

PMID- 14695787
TI  - Do there exist synergistic antitumor effects by coexpression of herpes simplex
      virus thymidine kinase with cytokine genes on human gastric cancer cell line
      SGC7901?
AB  - AIM: To evaluate the synergistic antitumor effects of herpes simplex virus
      thymidine kinase (HSV-TK) together with tumor necrosis factor alpha (TNF-alpha)
      or interleukin-2 (IL-2) gene expression on gastric cancer cell line SGC7901.
      METHODS: Recombinant vectors pL(TT)SN and pL(TI)SN, which express TK-IRES-TNF
      alpha and TK-IRES-IL-2 genes separately, as well as the control plasmids pL(TK)SN
      and pLXSN were employed to transfect PA317 cells respectively to generate the
      viruses that can stably express the objective genes through G418 selection. The
      gastric cancer cells were then transfected by the retroviral serum from the
      package cells and maintained in culture to determine the cell growth and
      apoptosis. The cytotoxic effects of HSV-TK together with TNF-alpha or IL-2 gene
      expression on the transfected cancer cells were evaluated by the cell viability
      and bystander effects in the presence of GCV supplemented in the cultural medium.
      RESULTS: Expression of recombinant proteins including TNF-alpha and IL-2 by
      stable transfectants was confirmed by Western blotting. The percentage of cell
      apoptosis in the SGC/0, SGC/TK-TNF-alpha, SGC/TK-IL-2 and SGC/TK clone was 2.3%,
      12.3%, 11.1% and 10.9% respectively at 24 h post-transfection. Cell growth status
      among all the experimental groups as judged by cell absorbance (A) at 570nm did
      not exhibit any significant difference (P>0.05); although it was noted to be
      slightly lower in the SGC/TT group. Cell survival rate in SGC/TI, SGC/TT and
      SGC/TK group was significantly decreased in a dose-dependent manner of GCV
      compared with that of the SGC/0 group (P<0.05-0.01). Among all studied cells, the
      SGC/TT was shown most sensitive to GCV with a half lethal dose of 0.5 mg/L(-1).
      In contrast, the survival rate of SGC/0 cells was not affected by the presence of
      GCV with the doses less than 10 mg/L(-1). The half lethal dose of GCV for SGC/0
      cells was more than 100 mg/L(-1). Marked bystander effect induced by SGC/TI,
      SGC/TT and SGC/TK cells was confirmed by the fact that 20% of these stable
      transfectants could kill 50% of the co-cultured cells, in which the most
      prominent bystander effect was found in the circumstance of SGC/TT presence.
      However, no significant difference of these variables was found among SGC/TI,
      SGC/TT and SGC/TK cells (P>0.05). CONCLUSION: The synergistic antitumor effects
      produced by the co-expression of HSV-TK with TNF-alpha or IL-2 genes were not
      present in the transfected SGC7901 cells. The mechanism underlying these
      phenomena was not known.

PMID- 14695788
TI  - Rising plasma nociceptin level during development of HCC: a case report.
AB  - AIM: Although liver cirrhosis is a predisposing factor for hepatocellular
      carcinoma (HCC), relatively few reports are available on HCC in primary biliary
      cirrhosis. High plasma nociceptin (N/OFQ) level has been shown in Wilson disease
      and in patients with acute and chronic pain. METHODS: We report a follow-up case
      of HCC, which developed in a patient with primary biliary cirrhosis. The tumor
      appeared 18 years after the diagnosis of PBC and led to death within two years.
      Alfa fetoprotein and serum nociceptin levels were monitored before and during the
      development of HCC. Nociceptin content was also measured in the tumor tissue.
      RESULTS: The importance and the curiosity of the presented case was the novel
      finding of the progressive elevation of plasma nociceptin level up to 17-fold
      (172 pg/mL) above the baseline (9.2+/-1.8 pg/mL), parallel with the elevation of
      alpha fetoprotein (from 13 ng/mL up to 3 480 ng/mL) during tumor development.
      Nociceptin content was more than 15-fold higher in the neoplastic tissue (0.16
      pg/mg) than that in the tumor-free liver tissue samples (0.01 pg/mg) taken during
      the autopsy. CONCLUSION: Results are in concordance with our previous observation
      that a very high plasma nociceptin level may be considered as an indicator for
      hepatocellular carcinoma.

PMID- 14695789
TI  - Isolation and structure elucidation of Sch 642305, a novel bacterial DNA primase
      inhibitor produced by Penicillium verrucosum.
AB  - A novel primase inhibitor, Sch 642305 (1), was isolated from the fermentation
      broth of the fungal culture Penicillium verrucosum. The structure of 1 was
      elucidated on the basis of MS and NMR spectroscopic data as a new and unusual
      bicyclic 10-membered macrolide. The absolute configuration of the asymmetric
      centers was determined by X-ray crystallographic analysis of the p-bromobenzoate
      derivative (3). Compound 1 exhibited inhibitory activity against bacterial DNA
      primase enzyme with an EC(50) of 70 microM.

PMID- 14695790
TI  - Antibacterial xanthones from the leaves of Garcinia nigrolineata.
AB  - Ten new 1,3,5-trioxygenated xanthones, nigrolineaxanthones J-S (1-10), one new
      quinone derivative, nigrolineaquinone A (11), and one new isoflavone-like
      compound, nigrolineaisoflavone A (12), were isolated from the leaves of Garcinia
      nigrolineata along with four known xanthones and friedelin. Among the xanthones,
      only nigrolineaxanthone N (5) showed significant antibacterial activity against
      methicillin-resistant Staphylococcus aureus.

PMID- 14695791
TI  - New cytotoxic steroidal alkaloids from the Philippine sponge Corticium niger.
AB  - Four new steroidal alkaloids, plakinamine I-K (1-3) and dihydroplakinamine K (4),
      were isolated from the marine sponge Corticium niger. The structures of these
      compounds were elucidated by interpretation of spectroscopic data. Compounds 1-4
      exhibit significant in vitro cytotoxicity.

PMID- 14695792
TI  - Cytochalasins Z4, Z5, and Z6, three new 24-Oxa[14]cytochalasans produced by Phoma
      exigua var. heteromorpha.
AB  - Cytochalasins Z4, Z5, and Z6, three new cytochalasans, were isolated from the
      wheat culture of Phoma exigua var. heteromorpha together with the known
      cytochalasins A, B, F, T, Z2, and Z3, 7-O-acetylcytochalasin B, and deoxaphomin.
      Z2 and Z3, together with Z1, have recently been described as new 24
      oxa[14]cytochalasans produced by Pyrenophora semeniperda, a fungus proposed for
      biological control of grass weeds. All three new cytochalasins were characterized
      as 24-oxa[14]cytochalasans by extensive use of NMR and MS techniques.
      Cytochalasins Z4 and Z5 proved to be structurally related to cytochalasin B,
      whereas Z6 was related to cytochalasin F. When assayed on tomato seedlings at 10(
      4) M, Z6 caused a very low inhibition of rootlet elongation (30%), whereas Z4 and
      Z5 were almost inactive. On brine shrimp, at the same concentration, only Z5 had
      a minor effect, with 20% mortality, whereas the other two metabolites proved to
      be inactive.

PMID- 14695793
TI  - The structure of Palau'amide, a potent cytotoxin from a species of the marine
      cyanobacterium Lyngbya.
AB  - Bioassay-guided fractionation of the extract of a species of Lyngbya from Palau
      has yielded Palau'amide (1), which had an IC(50) value of 13 nM against KB cells.
      The structure of 1 was elucidated by NMR analysis in a variety of solvents. In
      particular, a gradient-enhanced band-selective HMBC experiment allowed
      unambiguous assignment of HMBC correlations to carbon signals that were separated
      by 0.1 ppm. The relative stereochemistry and the absolute configurations of all
      but one (C-37) of the nine chiral centers were determined by NMR analysis of the
      alpha-methoxyphenylacetic acid (MPA) derivatives and chiral HPLC of the
      degradation products of 1. The assignment of S rather than R stereochemistry at C
      37 is discussed in detail.

PMID- 14695794
TI  - Heliotropamide, a novel oxopyrrolidine-3-carboxamide from Heliotropium
      ovalifolium.
AB  - Heliotropamide (1), a new alkaloid with a novel oxopyrrolidine-3-carboxamide
      central moiety, has been isolated as the major product of the dicholoromethane
      extract of Heliotropium ovalifolium aerial parts. Its structure was elucidated by
      spectrometric methods including ESI-HR, EI, D/CI mass spectrometry, (1)H, (13)C,
      and 2D NMR experiments, and chemical derivatization. Neither heliotropamide nor
      its acetylated derivative (1a) showed any antifungal activity against
      Cladosporium cucumerinum and Candida albicans, antibacterial activity against
      Bacillus subtilis, radical-scavenging properties in the DPPH test, or inhibitory
      potential toward acetylcholinesterase.

PMID- 14695795
TI  - Xanthanolides, germacranolides, and other constituents from Carpesium
      longifolium.
AB  - Three new xanthanolides, 1-3, along with nine known compounds, were isolated from
      the aerial parts of Carpesium longifolium. The structures of the new compounds
      were elucidated as 1beta,4beta-epoxy-5beta-hydroxy-10alphaH-xantha-11(13)-en
      12,8beta-olide (1), 1beta,4beta,4alpha,5beta-diepoxy-10alphaH,11alphaH-xantha
      12,8beta-olide (2), and 4-acetoxy-1beta,5beta-epoxy-10alphaH-xantha-11(13)-en
      12,8beta-olide (3) by spectroscopic methods including IR, EIMS, HRESIMS, and 1D
      and 2D NMR experiments. Parthenolide and michelenolide exhibited significant
      cytotoxic activity against cultured SMMC-7721 (human hepatoma) and HO-8910 (human
      ovarian carcinoma) cells.

PMID- 14695796
TI  - The macrocidins: novel cyclic tetramic acids with herbicidal activity produced by
      Phoma macrostoma.
AB  - Field isolates of Phoma macrostoma were obtained from diseased Canada thistle
      growing in several geographically diverse regions. Bleaching and chlorotic
      symptoms were present on the infected plants. The isolates grown in liquid
      culture were found to produce phytotoxic metabolites which also caused bleaching
      when applied foliarly to several broadleaf species. Bioassay-directed isolation
      led to the discovery of macrocidins A and B, the first representatives of a new
      family of cyclic tetramic acids. This new chemotype may offer significant
      potential as a template for herbicide design.

PMID- 14695797
TI  - Methylation of dihydroquercetin acetates: synthesis of 5-O
      methyldihydroquercetin.
AB  - The major products of methylation of dihydroquercetin (1, dhq) with diazomethane
      have been identified as 7-O-methyldhq (9), 7,3'-di-O-methyldhq (10), 7,4'-di-O
      methyldhq (11), and 7,3',4'-tri-O-methyldhq (2). With dhq 3,7,3',4'-tetraacetate
      (6), dhq 3,5,3',4'-tetraacetate (5), dhq 3,3',4'-triacetate (7), dhq 7,3',4'
      triacetate (8), and dhq 3-acetate (4) the same reaction affords mainly 5-O
      methyldhq 3,7,3',4'-tetraacetate (15), 7-O-methyldhq 3,5,3',4'-tetraacetate (13),
      7-O-methyldhq 3,3',4'-triacetate (14), 5-O-methyldhq 7,3',4'-triacetate (25), and
      7-O-methyldhq 3-acetate (12), respectively. The methylation of 8 is accompanied
      by intermolecular acetyl migration from phenolic oxygen to the hydroxy group of
      the heterocyclic ring. 5-O-Methyldhq (28) is accessible by deacetylation of 25.
      5,7-Di-O-methyldhq (29), four known methyl ethers, 13 new and three known methyl
      ether acetates of dhq, and six new isomers with 2,3-cis stereochemistry were
      spectroscopically identified.

PMID- 14695799
TI  - New cinnamylphenols from Dalbergia species with cancer chemopreventive activity.
AB  - Five new cinnamylphenols (1,3-diphenylpropenes), dalberatins A (1), B (2), C (3),
      D (4), and E (5), were isolated from plants of the Dalbergia species. They were
      characterized and tested for their inhibitory activities against Epstein-Barr
      virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in
      Raji cells. The cinnamylphenols were found to show remarkably potent activities.
      The result of the present investigation indicated that some of these
      cinnamylphenols might be valuable as potential cancer chemopreventive agents
      (anti-tumor promoters).

PMID- 14695798
TI  - Cytotoxic constituents of Aspergillus terreus from the rhizosphere of Opuntia
      versicolor of the Sonoran Desert.
AB  - A novel cyclopentenedione, asterredione (1), two new terrecyclic acid A
      derivatives, (+)-5(6)-dihydro-6-methoxyterrecyclic acid A (2) and (+)-5(6)
      dihydro-6-hydroxyterrecyclic acid A (3), and five known compounds, (+)
      terrecyclic acid A (4), (-)-quadrone (5), betulinan A (6), asterriquinone D (7),
      and asterriquinone C-1 (8), were isolated from Aspergillus terreus occurring in
      the rhizosphere of Opuntia versicolor, using bioassay-guided fractionation. Acid
      catalyzed reaction of 2 under mild conditions afforded 4, whereas under harsh
      conditions 2 yielded 5 and (-)-isoquadrone (9). Catalytic hydrogenation and
      methylation of 4 afforded 5(6)-dihydro-terrecyclic acid A (10) and (+)
      terrecyclic acid A methyl ester (11), respectively. The structures of 1-11 were
      elucidated by spectroscopic methods. All compounds were evaluated for
      cytotoxicity in a panel of three sentinel cancer cell lines, NCI-H460 (non-small
      cell lung cancer), MCF-7 (breast cancer), and SF-268 (CNS glioma), and were found
      to be moderately active. Cell cycle analysis of 2, 4, and 5 using the NCI-H460
      cell line indicated that 4 is capable of disrupting the cell cycle through an
      apparent arrest to progression at the G(1) and G(2)/M phases in this p53
      competent cell line. A pathway for the biosynthetic origin of asterredione (1)
      from asterriquinone D (7) is proposed.

PMID- 14695800
TI  - Tricholomalides A-C, new neurotrophic diterpenes from the mushroom Tricholoma sp.
AB  - Three new diterpenes, tricholomalides A-C (1-3), were isolated from the methanol
      extract of the fruiting body of Tricholoma sp. Their structures were elucidated
      on the basis of their spectral data, and the absolute configuration of 1 was
      determined by CD spectrum. Tricholomalides 1-3 significantly induced neurite
      outgrowth in rat pheochromocytoma cells (PC-12) at concentrations of 100 microM.

PMID- 14695801
TI  - Lucidenic acids P and Q, methyl lucidenate P, and other triterpenoids from the
      fungus Ganoderma lucidum and their inhibitory effects on Epstein-Barr virus
      activation.
AB  - A new triterpene acid, lucidenic acid P (1a), and two new triterpene acid methyl
      esters, methyl lucidenates P (1b) and Q (2b), were isolated and characterized
      from the fruiting body of the fungus Ganoderma lucidum. Their structures were
      elucidated on the basis of spectroscopic methods. In addition, eight known
      triterpene acids, lucidenic acids A (3a), C (4a), D(2) (5a), E(2) (6a), and F
      (7a) and ganoderic acids E (9a), F (10a), and T-Q (11a), and six known triterpene
      acid methyl esters, methyl lucidenates A (3b), D(2) (5b), E(2) (6b), F (7b), and
      L (8b) and methyl ganoderate F (10b), were isolated and identified from the
      fungus. All of the triterpenoids, with the exception of 7a, were evaluated with
      respect to their inhibitory effects on the induction of Epstein-Barr virus early
      antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells,
      which is known to be a primary screening test for antitumor promoters. All of the
      compounds tested showed potent inhibitory effects on EBV-EA induction (96-100%
      inhibition at 1 x 10(3) mol ratio/TPA).

PMID- 14695802
TI  - New dammarane triterpenes from the aerial parts of Ibicella lutea grown in
      Argentina.
AB  - Two new dammarane triterpenes have been isolated from the aerial parts of
      Ibicella lutea, 3-acetyl-24-epi-polacandrin (1) and 1,3-diacetyl-24-epi
      polacandrin (2), and were obtained along with the known compounds 20S,24S-epoxy
      3beta,12beta,25-trihydroxydammarane (3) and apigenin. The structures of compounds
      1 and 2 were deduced by spectroscopic studies and by chemical transformations
      leading to the preparation of derivatives 4-11. The structure and relative
      stereochemistry of 1 were verified by single-crystal X-ray analysis. The natural
      compounds and selected semisynthetic derivatives were evaluated against several
      tumor cells.

PMID- 14695803
TI  - Conyzasaponins I-Q, nine new triterpenoid daponins from Conyza blinii.
AB  - Nine new triterpenoid saponins, conyzasaponins I-Q (1-9), were isolated from the
      aerial parts of Conyza blinii. Their structures were established on the basis of
      extensive 1D and 2D NMR spectra as well as by chemical degradations. Among these
      compounds, conyzasaponins M-O (5-7) share a common pentasaccharide unit attached
      to C-28 of the aglycon, 28-O-beta-d-apiofuranosyl-(1-->3)-beta-d-xylopyranosyl-(1
      ->4)-[beta-d-apiofuranosyl-(1-->3)]-alpha-l-rhamnopyranosyl-(1-->2)-alpha-l
      arabinopyranosyl ester, which contains two apiofuranosyl residues. To the best of
      our knowledge, they are among the few examples of natural products possessing two
      apiofuranose units in a single sugar chain.

PMID- 14695804
TI  - New strongylophorines from the Okinawan marine sponge Petrosia (Strongylophora)
      corticata.
AB  - New strongylophorines-22 (1), -23 (2), -24 (3), and -25 (4) were isolated from
      the Okinawan sponge Petrosia (Strongylophora) corticata along with other known
      strongylophorines. The structures of these strongylophorines were determined on
      the basis of spectroscopic analysis and chemical conversions. Assessment was also
      made of the cytotoxicity of strongylophorines-1, -2, -3, -4, -22 (1), -23 (2),
      and -24 (3) toward HeLa cells.

PMID- 14695805
TI  - New triterpene glycosides from the stems of Anomospermum grandifolium.
AB  - Two new dammarane saponins identified as jujubogenin 3-O-alpha-l
      arabinofuranosyl(1-->2)-[beta-d-glucopyranosyl(1-->6) beta-d-glucopyranosyl(1-
      >3)]-alpha-l-arabinopyranoside (2) and jujubogenin 3-O-alpha-l-arabinofuranosyl(1
      ->2)-[6-O-[3-hydroxy-3-methylglutaryl]-beta-d-glucopyranosyl(1-->3)]-alpha-l
      arabinopyranoside (3) and a new lupane saponin, 3beta-hydroxylup-20(29)-en-27,28
      dioic acid 28-O-beta-d-glucopyranosyl(1-->2)-[beta-d-xylopyranosyl(1-->3)]-beta-d
      xylopyranosyl(1-->2)-beta-d-glucopyranoside ester (5), along with the known
      jujubogenin 3-O-alpha-l-arabinofuranosyl(1-->2)-[beta-d-glucopyranosyl(1-->3)]
      alpha-l-arabinopyranoside (1) and 3beta-hydroxylup-20(29)-ene-27,28-dioic acid
      (4), were isolated from the methanol extract of the stems of Anomospermum
      grandifolium. The structures of the new compounds were established by spectral
      analysis. Antimicrobial activity screening of compounds 1-3 revealed antifungal
      properties against C. albicans ATCC 3153 for compounds 2 and 3. The antibacterial
      and antifungal activities of the petroleum ether, chloroform, and methanol
      extracts of A. grandifolium stems were also evaluated.

PMID- 14695806
TI  - Cribrarione B, a new naphthoquinone pigment from the myxomycete Cribraria
      cancellata.
AB  - Cribrarione B (1), a new naphthoquinone pigment, has been isolated from the
      myxomycete Cribrariacancellata, and its structure was elucidated as 2,5,8
      trihydroxy-6-(1-hydroxyethyl)-[1,4]-naphthoquinone by NMR and mass spectral data.

PMID- 14695807
TI  - Occurrence of a high concentration of spider pheromones in the ascomycete fungus
      Hypoxylon truncatum.
AB  - A large amount of sex pheromones of the European spider Linyphia triangularis, 3R
      hydroxybutyric acid (1), its dimer 3R-(3R-hydroxybutyryloxy)butyric acid (2), and
      trimer 3R-[3R-(3R-hydroxybutyryloxy)butyryloxy]butyric acid (3) were isolated
      from the EtOAc extract of the Japanese inedible mushroom Hypoxylon truncatum.

PMID- 14695808
TI  - Discorhabdins S, T, and U, new cytotoxic pyrroloiminoquinones from a deep-water
      Caribbean sponge of the genus Batzella.
AB  - Discorhabdins S, T, and U (1-3), three new discorhabdin analogues, have been
      isolated from a deep-water marine sponge of the genus Batzella. These
      discorhabdin analogues showed in vitro cytotoxicity against PANC-1, P-388, and A
      549 cell lines. The isolation and structure elucidation of discorhabdins S, T,
      and U are described.

PMID- 14695809
TI  - Reversal of fluconazole resistance in multidrug efflux-resistant fungi by the
      Dysidea arenaria sponge sterol 9alpha,11alpha-epoxycholest-7-ene
      3beta,5alpha,6alpha,19-tetrol 6-acetate.
AB  - The sponge sterol 9alpha,11alpha-epoxycholest-7-ene-3beta,5alpha,6alpha,19-tetrol
      6-acetate (ECTA) (1) is the first marine natural product to reverse fluconazole
      resistance mediated by a Candida albicans MDR efflux pump. The IC(50) of
      fluconazole is decreased from 300 to 8.5 microM (35-fold enhancement) when
      combined with 1(3.8 microM). A revised C-6 configuration of 1 is established.

PMID- 14695810
TI  - Facile access to optically active labdane-type diterpenes from (+)-manool.
      Synthesis of (+)-coronarin E, (+)-15,16-epoxy-8(17),13(16),14-labdatriene, and
      (+)-labda-8(17),13(Z)-diene-15,16-diol.
AB  - An efficient method for the synthesis of (+)-coronarin E (1), (+)-15,16-epoxy
      8(17),13(16),14-labdatriene (2), and (+)-labda-8(17),13(Z)-diene-15,16-diol (3)
      from (+)-manool is described.

PMID- 14695811
TI  - A novel antibacterial iridoid and triterpene from Caiophora coronata.
AB  - Bioassay-guided fractionation of the antibacterial CH(2)Cl(2)-MeOH extract
      obtained from the aerial parts of the Argentinean plant Caiophora coronata led to
      the isolation of a new triterpene, 1beta,3beta-dihydroxyurs-12-en-27-oic acid, 1,
      and a new iridoid, 1alpha-methoxy-6alpha,10-dihydroxyisoepiiridomyrmecin
      (caiophoraenin), 2, along with the known iridoid isoboonein 3. Their structures
      were established by spectroscopic techniques (1D and 2D NMR, HRFABMS, FTIR). The
      MIC values of isolated compounds were determined against methicillin-sensitive
      (MSSA) and -resistant (MRSA) strains of Staphylococcus aureus, Bacillus subtilis
      (BS), vancomycin-resistant Enterococcus faecium (VREF), Escherichia coli (EC), E.
      coli imp (ECimp), and Candida albicans (CA). Compound 1 was found active against
      BS, MSSA, MRSA, VREF, and ECimp with MIC values of 2, 4, 4, 4, and 16 microg/mL,
      respectively.

PMID- 14695813
TI  - The discovery of ezetimibe: a view from outside the receptor.

PMID- 14695814
TI  - Self-association of okadaic acid upon complexation with potassium ion.
AB  - Okadaic acid (OA) is a toxin responsible for diarrhetic shellfish poisoning and
      is an extremely useful tool for studying processes that are regulated by
      phosphorylation, although the exact mechanism of action is still undetermined. We
      report on a study that proved the existence of OA in an unusual dimeric form when
      complexed with potassium ion. The proposed structure of this dimer is based on
      spectroscopic and conformational studies.

PMID- 14695815
TI  - Discovery of alpha,gamma-diketo acids as potent selective and reversible
      inhibitors of hepatitis C virus NS5b RNA-dependent RNA polymerase.
AB  - alpha,gamma-Diketo acids (DKA) were discovered from screening as selective and
      reversible inhibitors of hepatitis C virus NS5b RNA-dependent RNA polymerase. The
      diketo acid moiety proved essential for activity, while substitution on the gamma
      position was necessary for selectivity and potency. Optimization led to the
      identification of a DKA inhibitor of NS5b polymerase with IC(50) = 45 nM, one of
      the most potent HCV NS5b polymerase inhibitors reported.

PMID- 14695816
TI  - Discovery of small-molecule inhibitors of the ATPase activity of human
      papillomavirus E1 helicase.
AB  - The Boehringer Ingelheim compound collection was screened for inhibitors of the
      ATPase activity of human papillomavirus E1 helicase to develop antiviral agents
      that inhibit human papillomavirus (HPV) DNA replication. This screen led to the
      discovery of (biphenyl-4-sulfonyl)acetic acid 1, which inhibits the ATPase
      activity of HPV type 6 E1 helicase with a low micromolar IC(50) value. A hit-to
      lead exercise rapidly converted 1 into a low nanomolar lead series.

PMID- 14695817
TI  - Evaluation and comparison of 3D-QSAR CoMSIA models for CDK1, CDK5, and GSK-3
      inhibition by paullones.
AB  - With a view to the rational design of selective GSK-3beta inhibitors, 3D-QSAR
      CoMSIA models were developed for the inhibition of the three serine/threonine
      kinases CDK1/cyclin B, CDK5/p25, and GSK-3beta by compounds from the paullone
      inhibitor family. The models are based on the kinase inhibition data of 52
      paullone entities, which were aligned by a docking routine into the ATP-binding
      cleft of a CDK1/cyclin B homology model. Variation of grid spacing and column
      filtering were used during the optimization of the models. The predictive ability
      of the models was shown by a leave-one-out cross-validation and the prediction of
      an independent set of test compounds, which were synthesized especially for this
      purpose. Besides paullones with the basic indolo[3,2-d][1]benzazepine core, the
      test set comprised novel thieno[3',2':2,3]azepino[4,5-b]indoles,
      pyrido[2',3':2,3]azepino[4,5-b]indoles, and a pyrido[3',2':4,5]pyrrolo[3,2
      d][1]benzazepine. The best statistical values for the CoMSIA were obtained for
      the CDK1-models (r(2)() = 0.929 and q(2)() = 0.699), which were clearly superior
      to the models for CDK5 (r(2)() = 0.874 and q(2)() = 0.652) and GSK-3 (r(2)() =
      0.871 and q(2)() = 0.554).

PMID- 14695818
TI  - Molecular recognition of sub-micromolar inhibitors by the epinephrine
      synthesizing enzyme phenylethanolamine N-methyltransferase.
AB  - The crystal structures of human phenylethanolamine N-methyltransferase in complex
      with S-adenosyl-l-homocysteine (7, AdoHcy) and either 7-iodo-1,2,3,4
      tetrahydroisoquinoline (2) or 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine
      (3, LY134046) were determined and compared with the structure of the enzyme
      complex with 7 and 7-aminosulfonyl-1,2,3,4-tetrahydroisoquinoline (1, SK&F
      29661). The enzyme is able to accommodate a variety of chemically disparate
      functional groups on the aromatic ring of the inhibitors through adaptation of
      the binding pocket for this substituent and by subtle adjustments of the
      orientation of the inhibitors within the relatively planar binding site. In
      addition, the interactions formed by the amine nitrogen of all three inhibitors
      reinforce the hypothesis that this functional group mimics the beta-hydroxyl of
      norepinephrine rather than the amine. These studies provide further clues for the
      development of improved inhibitors for use as pharmacological probes.

PMID- 14695819
TI  - Lessons in molecular recognition: the effects of ligand and protein flexibility
      on molecular docking accuracy.
AB  - The key to success for computational tools used in structure-based drug design is
      the ability to accurately place or "dock" a ligand in the binding pocket of the
      target of interest. In this report we examine the effect of several factors on
      docking accuracy, including ligand and protein flexibility. To examine ligand
      flexibility in an unbiased fashion, a test set of 41 ligand-protein cocomplex X
      ray structures were assembled that represent a diversity of size, flexibility,
      and polarity with respect to the ligands. Four docking algorithms, DOCK, FlexX,
      GOLD, and CDOCKER, were applied to the test set, and the results were examined in
      terms of the ability to reproduce X-ray ligand positions within 2.0A heavy atom
      root-mean-square deviation. Overall, each method performed well (>50% accuracy)
      but for all methods it was found that docking accuracy decreased substantially
      for ligands with eight or more rotatable bonds. Only CDOCKER was able to
      accurately dock most of those ligands with eight or more rotatable bonds (71%
      accuracy rate). A second test set of structures was gathered to examine how
      protein flexibility influences docking accuracy. CDOCKER was applied to X-ray
      structures of trypsin, thrombin, and HIV-1-protease, using protein structures
      bound to several ligands and also the unbound (apo) form. Docking experiments of
      each ligand to one "average" structure and to the apo form were carried out, and
      the results were compared to docking each ligand back to its originating
      structure. The results show that docking accuracy falls off dramatically if one
      uses an average or apo structure. In fact, it is shown that the drop in docking
      accuracy mirrors the degree to which the protein moves upon ligand binding.

PMID- 14695820
TI  - HierVLS hierarchical docking protocol for virtual ligand screening of large
      molecule databases.
AB  - To provide practical means for rapidly scanning the extensive experimental
      combinatorial chemistry libraries now available for high-throughput screening
      (HTS), it is essential to establish computational virtual ligand screening (VLS)
      techniques to rapidly identify out of a large library all active compounds
      against a particular protein target. Toward this goal we developed HierVLS, a
      fast hierarchical docking approach that starts with a coarse grain conformational
      search over a large number of configurations filtered with a fast but crude
      energy function, followed by a succession of finer grain levels, using
      successively more accurate but more expensive descriptions of the ligand-protein
      solvent interactions to filter successively fewer cases. The final step of this
      procedure optimizes one configuration of the ligand in the protein site using our
      most accurate energy expression and description of the solvent, which would be
      impractical for all conformations and sites sampled in the coarse level. HierVLS
      is based on the HierDock approach, but rather than allowing an hour or more to
      determine the best binding site and energy for each ligands (as in HierDock), we
      have adapted our procedure so that it can lead to reliable results while using
      only 4 min (866 MHz Pentium III processor) per ligand. To validate the accuracy
      for HierVLS to predict the experimentally observed binding conformation, we
      considered 37 cocrystal structures comprising 11 target proteins. We find that
      HierVLS identifies the correct binding mode for all 37 cocrystals. In addition,
      the calculated binding energies correlate well with available experimental
      binding constants. To validate how well HierVLS can identify the correct ligand
      in an extensive library of decoys, we considered a library of over 10 000
      molecules. HierVLS identifies 26 out of the 37 cases in the top 2% ranked by
      binding affinity among the 10 037 molecules. The failures result from either
      metal-containing sites on the protein or water-mediated ligand-protein
      interactions, which we anticipate can be solved within the constraints of
      practical VLS. We then applied HierVLS to screen a 55000-compound virtual library
      against the target protein-tyrosine phosphatase 1B (ptp1b). The top 250 compounds
      by binding affinity included all six ptp1b cocrystal ligands added to the library
      plus three other experimentally confirmed binders. The best (top 1) binder is an
      experimentally confirmed positive. We conclude that HierVLS is useful for
      selecting leads for a particular target out of large combinatorial databases.

PMID- 14695821
TI  - Design, synthesis, molecular modeling studies, and calpain inhibitory activity of
      novel alpha-ketoamides incorporating polar residues at the P1'-position.
AB  - A series of novel alpha-ketoamides incorporating stereoisomeric residues with
      different electronic properties at the P(1)'-position were synthesized to study
      the electronic requirements for inhibitor binding to the S(1)'-subsite of calpain
      I. The results of the study suggested the presence of an acidic amino acid
      residue at the S(1)'-subsite of calpain I. For example, ester 1a (Cbz-l-Leu-l-Phe
      CO-d-Phe-OMe) was over 450-fold more potent than its carboxylic acid derivative
      2a (Cbz-l-Leu-l-Phe-CO-d-Phe-OH). Additionally, amidino derivative 3a (Cbz-l-Leu
      l-Phe-CONH-d-CH[C(NH)NH(2)]Bn) was about 6000-fold more potent than 2a.
      Furthermore, 4a (Cbz-l-Leu-l-Phe-CONHCH(2)Bn) was 12-fold less potent than its
      aza analogue 4b (Cbz-l-Leu-l-Phe-CONHNHBn). The results are consistent with the
      presence of an acidic amino acid residue at the S(1)'-subsite of calpain I. The
      acidic amino acid residue was found to be Glu261 via molecular modeling studies.

PMID- 14695822
TI  - Multiple active site corrections for docking and virtual screening.
AB  - Several docking programs are now available that can reproduce the bound
      conformation of a ligand in an active site, for a wide variety of experimentally
      determined complexes. However, these programs generally perform less well at
      ranking multiple possible ligands in one site. Since accurate identification of
      potential ligands is a prerequisite for many aspects of structure-based drug
      design, this is a serious limitation. We have tested the ability of two docking
      programs, FlexX and Gold, to match ligands and active sites for multiple
      complexes. We show that none of the docking scores from either program are able
      to match consistently ligands and active sites in our tests. We propose a simple
      statistical correction, the multiple active site correction (MASC), which greatly
      ameliorates this problem. We have also tested the correction method against an
      extended set of 63 cocrystals and in a virtual screening experiment. In all
      cases, MASC significantly improves the results of the docking experiments.

PMID- 14695823
TI  - Pyrrolobenzimidazoles linked to heterocycles and peptides. Design of DNA base
      pair specific phosphate hydrolyzing agents and novel cytotoxic agents.
AB  - Work in this laboratory has been involved with the design of aziridinyl quinone
      based cancer drugs (PBIs) capable of both recognizing the DNA major groove and
      cleaving the phosphate backbone upon reduction to the hydroquinone. The
      hydroquinone species recognizes the major groove of DNA at single base pairs by
      Hoogsteen-type hydrogen bonding. The present study extends recognition beyond a
      single base pair by adding amino acid residues to the 3-amino center of the PBI
      system. Thus, extension with proline or proline-glycine results in phosphate
      cleavage at 5'-AA-3' with insignificant N(7) guanine alkylation. Molecular models
      were used to validate the observed sequence specificity. This report also
      describes the design of PBIs not capable of DNA alkylation. Removal of major
      groove interactions by methylation or the presence of steric bulk prevented DNA
      alkylation reactions upon reductive activation. From these studies it was
      concluded that DNA alkyation was not necessary for PBI cytostatic and cytotoxic
      activity. For example, linkage of two phenylalanines to the PBI results in highly
      selective cytostatic and cytotoxic activity against melanoma, although this
      compound is a weak DNA alkylator.

PMID- 14695824
TI  - Synthesis and structure-activity relationships of 5,6,7,8-tetrahydro-4H
      thieno[3,2-b]azepine derivatives: novel arginine vasopressin antagonists.
AB  - A variety of novel heterocyclic compounds having thienoazepine, pyrroloazepine,
      furoazepine, and thienodiazepine skeletons were synthesized, most of which
      exhibited potent antagonism of [(3)H]-AVP specific binding in assays using rat
      liver (V1), rat kidney (V2), human platelet plasma membranes, and recombinant
      human CHO cells (V2), as well as antagonizing AVP-induced hypertension in rats
      (V1, intravenous) and showing a diuretic effect in rats (V2, oral). By detailed
      studies of the structure-activity relationships of these compounds, the
      thienoazepine derivative 1 was found to be a very potent combined V1 and V2
      antagonist. After further pharmacological and toxicological evaluation as well as
      physical properties, the hydrochloride 2 (JTV-605) of compound 1 was selected for
      clinical studies as a potent AVP antagonist with a long duration of action.

PMID- 14695825
TI  - Potent inhibitors of the Plasmodium falciparum enzymes plasmepsin I and II devoid
      of cathepsin D inhibitory activity.
AB  - The hemoglobin-degrading aspartic proteases plasmepsin I (Plm I) and plasmepsin
      II (Plm II) of the malaria parasite Plasmodium falciparum have lately emerged as
      putative drug targets. A series of C(2)-symmetric compounds encompassing the 1,2
      dihydroxyethylene scaffold and a variety of elongated P1/P1' side chains were
      synthesized via microwave-assisted palladium-catalyzed coupling reactions.
      Binding affinity calculations with the linear interaction energy method and
      molecular dynamics simulations reproduced the experimental binding data obtained
      in a Plm II assay with very good accuracy. Bioactive conformations of the
      elongated P1/P1' chains were predicted and agreed essentially with a recent X-ray
      structure. The compounds exhibited picomolar to nanomolar inhibition constants
      for the plasmepsins and no measurable affinity to the human enzyme cathepsin D.
      Some of the compounds also demonstrated significant inhibition of parasite growth
      in cell culture. To the best of our knowledge, these plasmepsin inhibitors
      represent the most selective reported to date and constitute promising lead
      compounds for further optimization.

PMID- 14695826
TI  - NMR structural characterization of peptide inhibitors bound to the Hepatitis C
      virus NS3 protease: design of a new P2 substituent.
AB  - A comparative NMR conformational analysis of three distinct tetrapeptide
      inhibitors of the Hepatitis C NS3 protease that differ at the 4-aryloxy
      substituted P2 proline position was undertaken. Specifically, transferred nuclear
      Overhauser effect experiments in combination with restrained systematic
      conformational searches were used to characterize the orientation of the P2 aryl
      substituents of these inhibitors when bound to the NS3 protease. Differences
      between free and bound conformations were also investigated. Analysis of the
      results allowed the design of a new P2 aromatic substituent, which significantly
      increased the potency of our inhibitors. The bound conformation of a specific
      competitive inhibitor having this novel P2 substituent is also described, along
      with a model of this inhibitor bound to the NS3 protease. This NS3
      protease/inhibitor complex model also supports a hypothetical stabilization role
      for the P2 residue of the substrates and/or inhibitors and further elucidates the
      subtle details of the binding of the P2 residue of substrate-based inhibitors.

PMID- 14695827
TI  - Three-dimensional quantitative structure-activity relationship modeling of
      cocaine binding by a novel human monoclonal antibody.
AB  - Human monoclonal antibodies (mAbs) designed for immunotherapy have a high
      potential for avoiding the complications that may result from human immune system
      responses to the introduction of nonhuman mAbs into patients. This study presents
      a characterization of cocaine/antibody interactions that determine the binding
      properties of the novel human sequence mAb 2E2 using three-dimensional
      quantitative structure-activity relationship (3D-QSAR) methodology. We have
      experimentally determined the binding affinities of mAb 2E2 for cocaine and 38
      cocaine analogues. The K(d) of mAb 2E2 for cocaine was 4 nM, indicating a high
      affinity. Also, mAb 2E2 displayed good cocaine specificity, as reflected in its
      10-, 1500-, and 25000-fold lower binding affinities for the three physiologically
      relevant cocaine metabolites benzoylecgonine, ecgonine methyl ester, and
      ecgonine, respectively. 3D-QSAR models of cocaine binding were developed by
      comparative molecular similarity index analysis (CoMSIA). A model of high
      statistical quality was generated showing that cocaine binds to mAb 2E2 in a
      sterically restricted binding site that leaves the methyl group attached to the
      ring nitrogen of cocaine solvent-exposed. The methyl ester group of cocaine
      appears to engage in attractive van der Waals interactions with mAb 2E2, whereas
      the phenyl group contributes to the binding primarily via hydrophobic
      interactions. The model further indicated that an increase in partial positive
      charge near the nitrogen proton and methyl ester carbonyl group enhances binding
      affinity and that the ester oxygen likely forms an intermolecular hydrogen bond
      with mAb 2E2. Overall, the cocaine binding properties of mAb 2E2 support its
      clinical potential for development as a treatment of cocaine overdose and
      addiction.

PMID- 14695828
TI  - Pyrrolo[1,3]benzothiazepine-based serotonin and dopamine receptor antagonists.
      Molecular modeling, further structure-activity relationship studies, and
      identification of novel atypical antipsychotic agents.
AB  - Recently we reported the pharmacological characterization of the 9,10
      dihydropyrrolo[1,3]benzothiazepine derivative (S)-(+)-8 as a novel atypical
      antipsychotic agent. This compound had an optimum pK(i) 5-HT(2A)/D(2) ratio of
      1.21 (pK(i) 5-HT(2A) = 8.83; pK(i) D(2) = 7.79). The lower D(2) receptor affinity
      of (S)-(+)-8 compared to its enantiomer was explained by the difficulty in
      reaching the conformation required to optimally fulfill the D(2) pharmacophore.
      With the aim of finding novel atypical antipsychotics we further investigated the
      core structure of (S)-(+)-8, synthesizing analogues with specific substituents;
      the structure-activity relationship (SAR) study was also expanded with the design
      and synthesis of other analogues characterized by a pyrrolo[2,1
      b][1,3]benzothiazepine skeleton, substituted on the benzo-fused ring or on the
      pyrrole system. On the 9,10-dihydro analogues the substituents introduced on the
      pyrrole ring were detrimental to affinity for dopamine and for 5-HT(2A)
      receptors, but the introduction of a double bond at C-9/10 on the structure of
      (S)-(+)-8 led to a potent D(2)/5-HT(2A) receptor ligand with a typical binding
      profile (9f, pK(i) 5-HT(2A)/D(2) ratio of 1.01, log Y = 8.43). Then, to reduce
      D(2) receptor affinity and restore atypicality on unsaturated analogues, we
      exploited the effect of specific substitutions on the tricyclic system of 9f.
      Through a molecular modeling approach we generated a novel series of potential
      atypical antipsychotic agents, with optimized 5HT(2A)/D(2) receptor affinity
      ratios and that were easier to synthesize and purify than the reference compound
      (S)-(+)-8. A number of SAR trends were identified, and among the analogues
      synthesized and tested in binding assays, 9d and 9m were identified as the most
      interesting, giving atypical log Y scores respectively 4.98 and 3.18 (pK(i) 5
      HT(2A)/D(2) ratios of 1.20 and 1.30, respectively). They had a multireceptor
      affinity profile and could be promising atypical agents. Compound 9d, whose
      synthesis is easier and whose binding profile is atypical (log Y score similar to
      that of olanzapine, 3.89), was selected for further biological investigation.
      Pharmacological and biochemical studies confirmed an atypical antipsychotic
      profile in vivo. The compound was active on conditioned avoidance response at 1.1
      mg/kg, a dose 100-times lower than that required to cause catalepsy (ED(50) >90
      mg/kg), it induced a negligible increase of prolactin serum levels after single
      and multiple doses, and antagonized the cognitive impairment induced by
      phencyclidine. In conclusion, the pharmacological profile of 9d proved better
      than clozapine and olanzapine, making this compound a potential clinical
      candidate.

PMID- 14695829
TI  - Design and synthesis of hydroxyethylene-based peptidomimetic inhibitors of human
      beta-secretase.
AB  - The hydroxyethylene (HE) transition state isostere was developed as a scaffold to
      provide potent, small molecule inhibitors of human beta-secretase (BACE). The
      previous work on the statine series proved critical to the discovery of HE
      structure-activity relationships. Compound 20 with the N-terminal isophthalamide
      proved to be the most potent HE inhibitor (IC(50) = 30 nM) toward BACE. Unlike
      the statine series, we identified HE inhibitors without carboxylic acids on the C
      terminus, leading to enhanced cell penetration and making them attractive
      candidates for further drug development in Alzheimer's disease.

PMID- 14695830
TI  - 10-Ketomorphinan and 3-substituted-3-desoxymorphinan analogues as mixed kappa and
      micro opioid ligands: synthesis and biological evaluation of their binding
      affinity at opioid receptors.
AB  - A series of 10-ketomorphinan analogues were synthesized, and their binding
      affinity at all three opioid receptors was investigated. In most cases, high
      affinity at micro and kappa receptors, and lower affinity at delta receptor was
      observed, resulting in good selectivity for micro and kappa receptors. A wide
      range of substituents can be accommodated on the nitrogen position. The N-(S)
      tetrahydrofurfuryl analogue 11 displayed the highest affinity at all three
      receptors. The N-cyclobutylmethyl analogue 13 gave both high affinity and
      selectivity at kappa receptor, and N-2-phenylethyl analogue 18 exhibited good
      affinity and selectivity at micro receptor. Further modifications of the 3
      substituent indicated that one H-bond donor was an essential requirement for good
      affinity at micro and kappa receptors. Similar modifications were investigated at
      the 3-OH group of morphinans: levorphanol (2a), cyclorphan (2b), and MCL-101 (2c)
      lacking the 10-keto group. The 3-amino bioisosteric analogues (40 and 41)
      displayed reasonably good affinity at micro and kappa receptors. The 3
      carboxamido replacement (compounds 46-48) in the morphinan subseries resulted in
      similar affinities comparable to their corresponding 3-OH congeners. The high
      affinity of these carboxamido analogues, along with their greater lipophilicity
      and metabolic stability, make them promising candidates for further
      pharmacological investigation.

PMID- 14695831
TI  - Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium
      species in vitro and in vivo.
AB  - The effects of a series of 102 bisphosphonates on the inhibition of growth of
      Entamoeba histolytica and Plasmodium falciparum in vitro have been determined,
      and selected compounds were further investigated for their in vivo activity.
      Forty-seven compounds tested were active (IC(50) < 200 microM) versus E.
      histolytica growth in vitro. The most active compounds (IC(50) approximately 4-9
      microM) were nitrogen-containing bisphosphonates with relatively large aromatic
      side chains. Simple n-alkyl-1-hydroxy-1,1-bisphosphonates, known inhibitors of
      the enzyme farnesylpyrophosphate (FPP) synthase, were also active, with optimal
      activity being found with C9-C10 side chains. However, numerous other nitrogen
      containing bisphosphonates known to be potent FPP synthase inhibitors, such as
      risedronate or pamidronate, had little or no activity. Several pyridine-derived
      bisphosphonates were quite active (IC(50) approximately 10-20 microM), and this
      activity was shown to correlate with the basicity of the aromatic group, with
      activity decreasing with increasing pK(a) values. The activities of all compounds
      were tested versus a human nasopharyngeal carcinoma (KB) cell line to enable an
      estimate of the therapeutic index (TI). Five bisphosphonates were selected and
      then screened for their ability to delay the development of amebic liver abscess
      formation in an E. histolytica infected hamster model. Two compounds were found
      to decrease liver abscess formation at 10 mg/kg ip with little or no effect on
      normal liver mass. With P. falciparum, 35 compounds had IC(50) values <200 microM
      in an in vitro assay. The most active compounds were also simple n-alkyl-1
      hydroxy-1,1-bisphosphonates, having IC(50) values around 1 microM. Five compounds
      were again selected for in vivo investigation in a Plasmodium berghei ANKA BALB/c
      mouse suppressive test. The most active compound, a C9 n-alkyl side chain
      containing bisphosphonate, caused an 80% reduction in parasitemia with no overt
      toxicity. Taken together, these results show that bisphosphonates appear to be
      useful lead compounds for the development of novel antiamebic and antimalarial
      drugs.

PMID- 14695833
TI  - Benzoxazinones as PPARgamma agonists. 2. SAR of the amide substituent and in vivo
      results in a type 2 diabetes model.
AB  - A series of benzoxazinones has been synthesized and tested for PPARgamma agonist
      activity. Synthetic approaches were developed to provide either racemic or chiral
      compounds. In vitro functional potency could be measured through induction of the
      aP2 gene, a target of PPARgamma. These studies revealed that compounds with large
      aliphatic chains at the nitrogen of the benzoxazinone were the most potent.
      Substitution of the chain was tolerated and in many cases enhanced the in vitro
      potency of the compound. Select compounds were further tested for metabolic
      stability, oral bioavailability in rats, and efficacy in db/db mice after 11 days
      of dosing. In vivo analysis with 13 and 57 demonstrated that the series has
      potential for the treatment of type 2 diabetes.

PMID- 14695832
TI  - Synthesis, in vitro evaluation, and antileishmanial activity of water-soluble
      prodrugs of buparvaquone.
AB  - Water-soluble phosphate prodrugs of buparvaquone (1), containing a
      hydroxynaphthoquinone structure, were synthesized and evaluated in vitro for
      improved topical and oral drug delivery against cutaneous and visceral
      leishmaniasis. The successful prodrug synthesis involved a strong base; e.g.,
      sodium hydride. Buparvaquone-3-phosphate (4a) and 3-phosphonooxymethyl
      buparvaquone (4b) prodrugs possessed significantly higher aqueous solubilities
      (>3.5 mg/mL) than the parent drug (</=0.03 microg/mL) over a pH range of 3.0-7.4.
      Moreover, 4a and 4b maintained adequate lipophilicity as indicated by
      distribution coefficients (log D) between 0.5 and 3.0 over this pH range. Both 4a
      and 4b were also shown to be substrates for alkaline phosphatase in vitro and
      thus are promising bioreversible prodrugs for the improved topical and oral
      bioavailability of 1. Buparvaquone and its prodrugs showed nanomolar or low
      micromolar ED(50) activity values against species that cause cutaneous
      leishmaniasis, e.g., L. major, L. amazonensis, L. aethiopica, L. mexicana, and L.
      panamensis and also L. donovani, which is the causative agent of visceral
      leishmaniasis. From these results, the human skin permeation of the prodrugs 4a
      and 4b were studied in vitro. While no buparvaquone permeated across post mortem
      skin in vitro during 72 h of experiments, both prodrugs 4a and 4b permeated
      readily through the skin. In addition, 4b easily released the parent drug in
      human skin homogenate and, therefore, is a promising prodrug candidate to deliver
      buparvaquone through the skin for the treatment of cutaneous leishmaniasis.

PMID- 14695834
TI  - Effects of pH on the cytotoxicity of sodium trioxodinitrate (Angeli's salt).
AB  - Tumor tissues have an acidic microenvironment with a pH from 6.0 to 7.0, whereas
      the intra- and extracellular milieu of normal cells is 7.4. We have found that
      the hydrolysis of sodium trioxodinitrate (Angeli's salt; 1) to hydroxyl radical
      (*OH) was 10 times higher at pH = 6.0 than at pH = 7.4. It is hypothesized that
      the formation of *OH in solutions of 1 reflects the hydrolysis of the latter
      compound to nitroxyl (HNO) which dimerizes to cis-hyponitrous acid (HO-N=N-OH; 3)
      with concomitant azo-type homolytic fission to N(2) and *OH. In weakly acidified
      solutions, 1 exhibited strong toxicity to cancer cells that was inhibited by
      scavengers of hydroxyl radical, whereas no toxicity was observed at pH = 7.4. In
      a subcutaneous xenograft model of pheochromocytoma, 1 markedly inhibited tumor
      growth at a dose that was nontoxic to nude mice. These data suggest that the H(+)
      amplified production of *OH from 1, and maybe other precursors of HNO, could be a
      selective mechanism for destruction cells with an acidic intra- or extracellular
      microenvironment.

PMID- 14695835
TI  - Chemical basis for the biological activity of imexon and related cyanoaziridines.
AB  - Chemical aspects of mode of action of imexon and related cyanoaziridines were
      studied. These compounds do not alkylate DNA nor react with the epsilon-amino
      groups of l-lysine, despite the presence of an aziridine ring. They do react
      readily with biologically important sulfhydryl compounds to give products derived
      from either aziridine ring opening, interaction with the cyano group of
      cyanoaziridines, or opening of the iminopyrrolidone ring of imexon. The products
      from reactions of imexon and related cyanoaziridines with thiols are not as
      potent as their parent compounds against tumor cells. These results are
      consistent with biological studies that show that the mechanism of cytotoxicity
      involves thiol depletion followed by oxidative stress leading to apoptosis.

PMID- 14695836
TI  - Characteristic physical properties and structural fragments of marketed oral
      drugs.
AB  - An increasingly competitive pharmaceutical market demands improvement in the
      efficiency and probability of drug candidate discovery. Usually these new drug
      candidates are targeted for oral administration, so a detailed understanding of
      the molecular-level properties that relate to optimal pharmacokinetics is a
      critical step toward improving the probability of selecting successful clinical
      candidates. Although the characteristics of druglike molecules have been
      previously discussed in the literature, the importance of this topic sustains a
      continued interest for additional perspective and further detailed statistical
      analyses. In this contribution, we approach the analysis from the perspective of
      profiling distinguishing features of orally administered drugs. We have compiled
      both structural and route-administration information for a total of 1729 marketed
      drugs to provide a solid basis for developing a new perspective on the
      characteristics of over 1000 orally administered drugs. The molecular properties
      and most commonly occurring structural elements are statistically analyzed to
      capture the differences between routes of administration, as well as between
      marketed drugs and SAR or clinical compounds. We find that, with respect to other
      routes of administration, oral drugs tend to be lighter and have fewer H-bond
      donors, acceptors, and rotatable bonds than drugs with other routes of
      administration. These differences are particularly pronounced when comparing the
      mean values for oral vs injectable drugs. We also demonstrate that the mean
      property values for oral drugs do not vary substantially with respect to launch
      date, suggesting that the range of acceptable oral properties is independent of
      synthetic complexity or targeted receptor. Finally, we note that, while these
      properties are descriptive of each class, they are not necessarily predictive of
      what class any particular drug will reside in, since there is significant overlap
      in the acceptable ranges found for each drug class.

PMID- 14695837
TI  - Cyclodextrin-derived diorganyl tellurides as glutathione peroxidase mimics and
      inhibitors of thioredoxin reductase and cancer cell growth.
AB  - Water-soluble diorganyl tellurides of the alkyl aryl or dialkyl type were
      prepared by treatment of mono-6-tosyl-beta-cyclodextrin with sodium
      alkanetellurolates or arenetellurolates or sodium telluride. The novel
      cyclodextrin-derived organotelluriums were evaluated for their capacity to
      catalyze the reduction of hydrogen peroxide, tert-butyl hydroperoxide, and cumene
      hydroperoxide in the presence of glutathione, NADPH, and GSSG-reductase (coupled
      reductase assay). Cyclodextrins 4d and 4e, carrying 4-(N,N
      dimethylamino)phenyltelluro and n-butyltelluro groups, respectively, were the
      most efficient glutathione peroxidase mimics. Reduction of lipophilic cumene
      hydroperoxide often proceeded 10-20 times faster than reduction of the more
      hydrophilic hydroperoxides, which cannot bind into the hydrophobic interior of
      the cyclodextrin. Thus, it seems that the carbohydrate moiety acts as a binding
      site for the hydroperoxide substrate. The cyclodextrin derivatives were also
      evaluated for their capacity to inhibit thioredoxin reductase/thioredoxin and
      cancer cell growth in culture. IC(50) values for inhibition of thioredoxin or
      thioredoxin/thioredoxin reductase were in the submicromolar range for the best
      inhibitors (compounds 4d and 5). Two of the compounds (4c and 5) were found to
      inhibit the growth of MCF-7 cells in culture with IC(50) values in the low
      micromolar range.

PMID- 14695838
TI  - Folate-synthesizing enzyme system as target for development of inhibitors and
      inhibitor combinations against Candida albicans-synthesis and biological activity
      of new 2,4-diaminopyrimidines and 4'-substituted 4-aminodiphenyl sulfones.
AB  - The paper describes the design, synthesis, and testing of inhibitors of folate
      synthesizing enzymes and of whole cell cultures of Candida albicans. The target
      enzymes used were dihydropteroic acid synthase (SYN) and dihydrofolate reductase
      (DHFR). Several series of new 2,4-diaminopyrimidines were synthesized and tested
      as inhibitors of DHFR and compared with their activity against DHFR derived from
      mycobacteria and Escherichia coli. To test for selectivity, also rat DHFR was
      used. A series of substituted 4-aminodiphenyl sulfones was tested for inhibitory
      activity against SYN and the I(50) values compared to those obtained previously
      against Plasmodium berghei- and E. coli-derived SYN. Surprisingly, QSAR equations
      show very similar structural dependencies. To find an explanation for the large
      difference in the I(50) values observed for enzyme inhibition (SYN, DHFR) and for
      inhibition of cell cultures of Candida, mutant strains with overexpressed efflux
      pumps and strains in which such pumps are deleted were included in the study and
      the MICs compared. Efflux pumps were responsible for the low activity of some of
      the tested derivatives, others showed no increase in activity after pumps were
      knocked out. In this case it may be speculated that these derivatives are not
      able to enter the cells.

PMID- 14695839
TI  - Syntheses, calcium channel agonist-antagonist modulation activities, and nitric
      oxide release studies of nitrooxyalkyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2,1,3
      benzoxadiazol-4-yl)pyridine-5-carboxylate racemates, enantiomers, and
      diastereomers.
AB  - A novel group of hybrid calcium channel (CC) modulators was prepared where the
      isopropyl ester moiety of isopropyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2,1,3
      benzoxadiazol-4-yl)pyridine-5-carboxylate (PN 202-791) was replaced by a variety
      of nitric oxide (*NO) donor nitrooxyalkyl ester substituents. Enantiomers, or
      diastereomers, having the (R)-configuration at the C-4 position of the 1,4
      dihydropyridine ring (1,4-DHP) exhibited more potent in vitro CC antagonist
      activity on guinea pig ileum longitudinal smooth muscle (GPILSM) than compounds
      having the (4S)-configuration. None of the nitrooxyalkyl compounds exhibited a
      contraindicated CC agonist effect on GPILSM that would cause smooth muscle
      contraction. Structure-activity studies showed the enantiomers having the (S)
      configuration at the C-4 position of the 1,4-DHP ring or diastereomers having the
      a (4S)-configuration at the C-4 position of the 1,4-DHP ring in conjunction with
      a (1R-)-1-methyl-2-nitrooxyethyl ester substituent exhibited the most potent
      cardiac CC agonist (positive inotropic) activity on guinea pig left atrium
      (GPLA). This class of compounds releases *NO in vitro that is enhanced by the
      presence of a thiol such as N-acetylcysteamine. The novel *NO donor (-)-(S,R)-1
      methyl-2-nitrooxyethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2,1,3-benzoxadiazol-4
      yl)pyridine-5-carboxylate [(-)-(S,R)-38], which acts as a dual cardioselective
      calcium channel agonist (GPLA)/smooth muscle selective calciumchannel antagonist
      (GPILSM), is a useful lead compound for drug discovery targeted to the treatment
      of congestive heart failure, and it provides a useful research probe to study the
      structure-function relationship of calcium channels.

PMID- 14695840
TI  - Synthesis and biological evaluation of analogues of 7-chloro-4,5-dihydro-4- oxo-8
      (1,2,4-triazol-4-yl)-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylic acid (TQX-173)
      as novel selective AMPA receptor antagonists.
AB  - In recent papers (Catarzi, D.; et al. J. Med. Chem. 2000, 43, 3824-3826; 2001,
      44, 3157-3165) we reported chemical and biological studies on 4,5-dihydro-4-oxo
      1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates (TQXs) bearing different nitrogen
      containing heterocycles at position-8. In particular, from these studies it
      emerged that both the 7-chloro-4,5-dihydro-4-oxo-8-(1,2,4-triazol-4-yl)-1,2,4
      triazolo[1,5-a] quinoxaline-2-carboxylic acid TQX-173 (compound B) and its
      corresponding ethyl ester (compound A) were the most active and selective
      compounds of this series. In pursuing our investigation on the structure-activity
      relationships of these TQX derivatives, different electron-withdrawing groups
      (CF(3), NO(2)) were introduced at position 7 on the TQX ring system, replacing
      the 7-chloro substituent of B and of other selected 8
      heteroaryltriazoloquinoxaline-2-carboxylates previously described. All the newly
      synthesized compounds were biologically evaluated for their binding at the
      Gly/NMDA, AMPA, and KA high-affinity receptors. Gly/NMDA binding assays were
      performed to assess the selectivity of the reported compounds toward the AMPA
      receptor. Compounds endowed with micromolar binding affinity for the KA high
      affinity binding site were also evaluated for their binding at the KA low
      affinity receptor. Some selected compounds were also tested for their functional
      antagonist activity at the AMPA and NMDA receptor-ion channel complex. The
      results obtained in this study have pointed out that 4,5-dihydro-7-nitro-4-oxo-8
      (3-carboxypyrrol-1-yl)-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylic acid (9b)
      and its corresponding ethyl ester (9a) are the most potent and selective AMPA
      receptor antagonists reported to date among the TQX series.

PMID- 14695841
TI  - Antimycobacterial agents. 1. Thio analogues of purine.
AB  - Thio analogues of purine, pyridine, and pyrimidine were prepared based on the
      initial activity screening of several analogues of these heterocycles against
      Mycobacterium tuberculosis (Mtb). Certain 6-thio-substituted purine analogues
      described herein showed moderate to good inhibitory activity. In particular, two
      purine analogues 9-(ethylcarboxymethyl)-6-(decylthio)-9H-purine (20) and 9
      (ethylcarboxymethyl)-6-(dodecylthio)-9H-purine (21) exhibited MIC values of 1.56
      and 0.78 microg/mL respectively against the Mtb H(37)Rv strain. N(9)-Substitution
      apparently enhances the antimycobacterial activity in the purine series described
      herein.

PMID- 14695842
TI  - Highly diverse heparan sulfate analogue libraries: providing access to expanded
      areas of sequence space for bioactivity screening.
AB  - Structurally diverse heparan sulfate analogue libraries were produced
      chemicoenzymatically from heparin. They possess vastly more heterogeneity than
      tissue heparan sulfates, expand the sequence space available for screening, and
      can help identify minimal structural features associated with activity. Library
      components are likely to exhibit fewer nonspecific interactions and side-effects
      than heparin or simple chemically modified heparin. A strategy for their use is
      illustrated for the fibroblast growth factor-receptor tyrosine kinase signaling
      system.

PMID- 14695843
TI  - Coagulopathies associated with lymphoproliferative disorders.

PMID- 14695844
TI  - Are antibiotics the treatment of choice for gastric lymphoma?
AB  - There is compelling evidence supporting the link between Helicobacter pylori
      infection and gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and it
      seems undeniable that eradication of H. pylori with antibiotics can be
      effectively used as the sole initial treatment of localized (ie, confined to the
      gastric wall) gastric MALT lymphoma. This treatment is the best studied
      therapeutic approach, with more than 20 reported studies confirming that
      histologic regression of the lymphoma can be achieved in most cases. However,
      antibiotic treatments seem to suppress but not eradicate the neoplastic clone,
      and MALT lymphoma relapses have been seen years after treatment. Molecular follow
      up studies revealed the persistence of the malignant clone in more than 50% of
      the cases in histologic remission after antibiotic therapy. The clinical
      significance of this finding is still unclear. Transient and self-limiting
      histologic and molecular relapses can also occur. Therefore, a careful long-term
      follow-up is mandatory for all of the patients who received antibiotic treatment.

PMID- 14695845
TI  - What is the treatment of choice for advanced-stage Hodgkin's lymphoma: ABVD,
      Stanford V, or BEACOPP?
AB  - The combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is
      the most commonly used chemotherapy regimen in North America for the treatment of
      advanced-stage Hodgkin's lymphoma. Although 60% to 70% of patients with stages
      III and IV Hodgkin's lymphoma may be cured with ABVD, many patients relapse or
      progress despite standard therapy. Two new regimens, BEACOPP (bleomycin,
      etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and
      prednisone) and Stanford V (vinblastine, doxorubicin, vincristine, bleomycin,
      mustard, etoposide, and prednisone), have shown short-term (3-5 years) overall
      survival results of 90% or better. Although the results of pilot studies using
      these regimens and one randomized trial with BEACOPP look promising, the
      toxicities are substantial. To evaluate overall benefit, two large intergroup
      trials are underway comparing ABVD versus BEACOPP (European Organization for
      Research and Treatment of Cancer 20012) and ABVD versus Stanford V (E2496) in
      advanced Hodgkin's lymphoma.

PMID- 14695846
TI  - Late complications of therapy of Hodgkin's disease: prevention and management.
AB  - Patients diagnosed with Hodgkin's disease have a high cure rate. However, long
      term survivors of the disease are at significantly increased risk for many late
      complications. The most serious late effects faced by these patients include the
      development of a second malignancy or cardiovascular disease. Ongoing trials
      investigating treatment reduction, including using lower radiation dose, smaller
      radiation field size, and abbreviated chemotherapy, will hopefully help in
      limiting the treatment-related complications. Continued long-term follow-up of
      survivors, careful documentation of the broad range of late effects,
      identification of risk factors, development and evaluation of screening programs,
      and preventative therapy for specific late complications are important steps in
      improving the survival and quality of life of patients who have been cured of
      Hodgkin's disease.

PMID- 14695847
TI  - A new standard treatment for chronic myelogenous leukemia.

PMID- 14695848
TI  - Hematopoietic growth factors for acute myelogenous leukemia.

PMID- 14695849
TI  - Treatment options for newly diagnosed patients with adult acute lymphoblastic
      leukemia.
AB  - The treatment of adults with acute lymphoblastic leukemia (ALL) has been modeled
      on therapy developed for childhood ALL. The similarity between childhood and
      adult forms of this disease allows for inferences to be drawn from experience in
      the pediatric population. However, adults with ALL have far poorer outcome when
      compared to children. Some of this difference can be attributed in ability to
      tolerate intensive therapy coupled with an increased incidence of unfavorable
      cytogenetic subgroups and a decreased incidence of favorable cytogenetic
      subgroups. Treatment of adult ALL is typically divided into four broad
      categories: induction, consolidation, maintenance, and central nervous system
      prophylaxis. Despite three decades of clinical investigation for devising
      improved treatment programs for adults with ALL, no single program has emerged as
      the standard. Here we review classification, prognostic features, current
      treatment programs, and new advances as applied to adult patients with newly
      diagnosed ALL.

PMID- 14695850
TI  - Treatment options for newly diagnosed patients with chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is an indolent B-cell malignancy for which
      early intervention has not been shown to extend survival. However, there are many
      agents available that are active in this disease. Alkylating agents, the purine
      analogs, and monoclonal antibodies have all been shown to result in high response
      rates in patients with previously treated and untreated CLL. These classes of
      agents have been combined based on in vitro data demonstrating synergism. The
      purine analogs alone or in combination with alkylating agents and monoclonal
      antibodies result in greater response rates compared with alkylating agent-based
      therapy alone. However, improvement in overall survival and cure of patients with
      CLL has yet to be realized with these available regimens. The best initial
      therapy of patients with CLL remains a matter of debate.

PMID- 14695851
TI  - Treatment options for newly diagnosed patients with chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is characterized by a 9:22 translocation resulting
      in production of a chimeric BCR-ABL fusion protein that has constitutive tyrosine
      kinase activity and drives leukemic transformation. Imatinib mesylate, a
      selective inhibitor of BCR-ABL, has been introduced into clinical trials with
      favorable toxicity and impressive activity at all disease stages. In a phase III
      study of diagnosed chronic phase CML, imatinib mesylate was superior to
      interferon plus cytarabine in cytogenetic response, freedom from disease
      progression, and tolerability. Hematopoietic stem cell transplantation remains
      the only established cure for CML. Recent reports show continued improvements
      with survivals after matched sibling grafts greater than 80% at 3 to 5 years.
      Therefore, recent advances in conventional and transplant therapy have improved
      treatment options for newly diagnosed patients. Sensitive and specific monitoring
      techniques developed for CML may help further refine treatment with regard to
      using these and other emerging therapies.

PMID- 14695852
TI  - Bortezomib therapy for myeloma.

PMID- 14695853
TI  - Stem cell transplantation for myeloma.

PMID- 14695854
TI  - Insights from the gene expression profiling of multiple myeloma.
AB  - Recent gene expression profiling using high throughput sequencing and microarray
      analysis of multiple myeloma has shed new light on this morphologically
      homogeneous yet clinically heterogeneous disease. The biology of the disease has
      been interrogated in studies, which reveal that patients have unique gene
      expression clusters that correlate with disease severity. These studies have also
      revealed that some myeloma cells have gene expression characteristics that
      resemble the molecular profile of late-stage B cells. Expression profiling can
      identify hallmark immunoglobulin translocations and other common structural
      genetic changes that impart prognostic significance. Molecular profiling has been
      demonstrated to be of value in pharmacogenomic studies predicting response to
      therapy and revealing novel therapeutic targets. These studies are providing
      insight into many previously unexplained features of this difficult disease.

PMID- 14695855
TI  - Mental health services for residents of care homes.

PMID- 14695856
TI  - Assess first, admit second.

PMID- 14695857
TI  - Anaesthesia and the older surgical patient: something old, something new,
      something borrowed.

PMID- 14695858
TI  - Blood pressure in acute stroke.
AB  - Elevated systolic blood pressure levels (> or =160 mmHg) are a common
      complication of acute stroke, affecting up to 60% of patients, and providing an
      immediate management dilemma in the 40% of acute stroke patients on pre-existing
      antihypertensive therapy. There are theoretical reasons for both lowering blood
      pressure in the acute stroke situation, as well as leaving raised levels
      untreated. Furthermore, low systolic blood pressure levels (< or =140 mmHg),
      though a less common problem affecting approximately 20% of patients, may also be
      associated with increased morbidity and mortality. However, limited data exists
      from randomised, placebo-controlled trials to inform as to the optimum management
      of acute stroke blood pressure. This review will consider the evidence for and
      against the therapeutic manipulation of acute stroke blood pressure, and discuss
      the information currently available from observational and therapeutic
      intervention trials, as well as consider the ongoing clinical trials in this
      area.

PMID- 14695860
TI  - The value of specialist clinical assessment of older people prior to entry to
      care homes.
AB  - OBJECTIVE: to ascertain the value of employing a specialist clinician's
      contribution to the assessment of older people prior to care home entry. DESIGN:
      randomised controlled trial. METHOD: 256 older people at risk of care home entry
      were randomly allocated to either a control group, who received the usual care
      management assessment, or to an experimental group who, in addition, received a
      clinical assessment by a geriatrician or old age psychiatrist. The value of the
      additional assessment was evaluated by an analysis of clinical recommendations,
      questionnaires eliciting the views of stakeholders and research interviews with
      older people and their carers at initial assessment and 6 months. Data on service
      use and costs over 6 months and on destination at 6 and 12 months were also
      collected. RESULTS: the clinical assessment uncovered covert morbidity previously
      unknown to care managers particularly in respect of cognitive impairment and was
      adjudged acceptable to the different stakeholders involved. Those receiving the
      clinical assessment experienced less deterioration in their physical functioning,
      had less contact with nursing homes and emergency services and their carers
      experienced reduced levels of distress. Overall, the costs of care for those
      receiving the assessment were no greater with NHS costs actually lower.
      CONCLUSIONS: the potential benefits in involving specialist clinicians in the
      assessment process include identifying previously undiagnosed conditions and
      enhancing care managers' decision making. Such an assessment could be provided at
      a modest marginal cost. The approach is fully compatible with proposals for the
      role of the community geriatrician and commensurate with current good clinical
      practice in old age psychiatry.

PMID- 14695861
TI  - Vitamin B12 and folate deficiency in later life.
AB  - OBJECTIVES: to examine the prevalence of vitamin B12 deficiency and folate
      deficiency in later life in representative samples of the elderly population in
      the United Kingdom. DESIGN: a population-based cross-sectional analysis of 3,511
      people aged 65 years or older from three studies was used to estimate the age
      specific prevalence of vitamin B12 deficiency and of folate deficiency. Vitamin
      B12 deficiency is conventionally diagnosed if serum vitamin B12 < 150 pmol/l
      ('low vitamin B12'). We defined 'metabolically significant vitamin B12
      deficiency' as vitamin B12 < 200 pmol/l and blood total homocysteine >20 micro
      mol/l. Folate deficiency, which usually refers to serum folate <5 nmol/l, was
      defined as 'metabolically significant' if serum folate was <7 nmol/l and
      homocysteine >20 micro mol/l. RESULTS: the prevalence of vitamin B12 deficiency,
      whether defined as low vitamin B12 or metabolically significant vitamin B12
      deficiency increased with age in all three studies, from about 1 in 20 among
      people aged 65-74 years to 1 in 10 or even greater among people aged 75 years or
      greater. The prevalence of folate deficiency also increased with age, and was
      similar to that for vitamin B12 deficiencies, but only about 10% of people with
      low vitamin B12 levels also had low folate levels. CONCLUSION: the high
      prevalence of vitamin B12 and folate deficiency observed in older people
      indicates a particular need for vigilance for deficiency of these vitamins.
      Reliable detection and treatment of vitamin deficiency could reduce the risk of
      deficiency-related disability in old age.

PMID- 14695862
TI  - Changes in arterial oxygen saturation before and after enteral feeding tube
      insertion in dysphagic stroke patients.
AB  - OBJECTIVE: to determine whether insertion of nasogastric or percutaneous
      endoscopic gastrostomy feeding tubes is associated with hypoxaemia. METHODS:
      dysphagic stroke patients had their arterial oxygen saturation measured by pulse
      oximetry continuously for 10 minutes before, during and after tube insertion.
      RESULTS: in 14 patients nasogastric tube insertion had little effect on oxygen
      saturation. Six patients maintained oxygen saturation during percutaneous
      endoscopic gastrostomy insertion (whilst on 2 litres oxygen/min) but had a
      significantly lower median oxygen saturation (P = 0.03) after the procedure (when
      oxygen was discontinued) and four of these had oxygen saturation of < or =90%.
      CONCLUSIONS: in this small group of stroke patients, difficult insertions of
      nasogastric and percutaneous endoscopic gastrostomy tubes were associated with
      moderate hypoxaemia. Clinicians should be aware of the potential impact of tube
      insertion and ensure patients are appropriately monitored and if necessary
      receive supplemental oxygen, after as well as during the procedure.

PMID- 14695863
TI  - A randomised, controlled comparison of different calcium and vitamin D
      supplementation regimens in elderly women after hip fracture: The Nottingham Neck
      of Femur (NONOF) Study.
AB  - BACKGROUND: survivors of hip fracture are at 5- to 10-fold risk of a second hip
      fracture. There is little consensus about secondary prevention. Many are given
      calcium and vitamin D, but the evidence supporting this is circumstantial.
      OBJECTIVE: to compare the effects of different calcium and vitamin D
      supplementation regimens on bone biochemical markers, bone mineral density and
      rate of falls in elderly women post-hip fracture. DESIGN: randomised controlled
      trial. SETTING: orthogeriatric rehabilitation ward. METHODS: 150 previously
      independent elderly women, recruited following surgery for hip fracture, were
      assigned to receive a single injection of 300,000 units of vitamin D(2), injected
      vitamin D(2) plus 1 g/day oral calcium, 800 units/day oral vitamin D(3) plus 1
      g/day calcium, or no treatment. Follow-up was one year, with measurement of 25
      hydroxyvitamin D, parathyroid hormone, bone mineral density, and falls. RESULTS:
      mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in
      all the actively treated groups, more so in the group receiving combined oral
      vitamin D and calcium. Twenty per cent of participants injected with vitamin D
      were deficient in 25-hydroxyvitamin D a year later. Bone mineral density showed
      small but statistically significant differences of up to 4.6% between actively
      treated groups and placebo. Relative risk of falling in the groups supplemented
      with vitamin D was 0.48 (95% CI 0.26-0.90) compared with controls. CONCLUSION:
      Vitamin D supplementation, either orally or with injected vitamin D, suppresses
      parathyroid hormone, increases bone mineral density and reduces falls. Effects
      may be more marked with calcium co-supplementation. The 300,000 units of injected
      vitamin D may not last a whole year.

PMID- 14695864
TI  - The efficacy of a specific balance-strategy training programme for preventing
      falls among older people: a pilot randomised controlled trial.
AB  - BACKGROUND: older people participate in exercise programmes to reduce the risk of
      falls but no study has investigated a specific balance strategy training
      intervention presented in a workstation format for small groups. OBJECTIVE: to
      determine whether a specific balance strategy training programmeme delivered in a
      workstation format was superior to a community based exercise class programme for
      reducing falls. DESIGN: a randomised controlled trial model. SETTING:
      Neurological Disorders, Ageing and Balance Clinic, Department of Physiotherapy,
      The University of Queensland. SUBJECTS: 73 males and females over 60 years,
      living independently in the community and who had fallen in the previous year
      were recruited. METHODS: all subjects received a falls risk education booklet and
      completed an incident calendar for the duration of the study. Treatment sessions
      were once a week for 10 weeks. Subject assessment before and after intervention
      and at 3 months follow-up included number of falls, co-morbidities, medications,
      community services and activity level, functional motor ability, clinical and
      laboratory balance measures and fear of falling. RESULTS: all participants
      significantly reduced the number of falls (P < 0.000). The specific balance
      strategy intervention group showed significantly more improvement in functional
      measures than the control group (P = 0.034). Separate group analyses indicated
      significantly improved performance in functional motor ability and most clinical
      balance measures for the balance group (P < 0.04). The control group only
      improved in TUG and TUGcog. CONCLUSIONS: the results provide evidence that all
      participants achieved a significant reduction in falls. Specific balance strategy
      training using workstations is superior to traditional exercise classes for
      improving function and balance.

PMID- 14695865
TI  - Consequences of falling in older men and women and risk factors for health
      service use and functional decline.
AB  - OBJECTIVES: (1) to examine consequences of falls in older men and women and (2)
      to examine risk factors for health service use and functional decline among older
      fallers. METHODS: the study was performed within the Longitudinal Aging Study
      Amsterdam. In 1998/1999, potential risk factors were assessed during the third
      data collection. In 1999/2000, 204 community-dwelling persons (> or =65 years)
      who reported at least one fall in the year before the interview, were asked about
      consequences of their last fall, including physical injury, health service use,
      treatment and functional decline (i.e. decline in functional status, social and
      physical activities). RESULTS: as a consequence of falling, respondents reported
      physical injury (68.1%), major injury (5.9%), health service use (23.5%),
      treatment (17.2%), and decline in functional status (35.3%), and social (16.7%)
      and physical activities (15.2%). Using multivariate logistic regression, specific
      risk factors for health service use after falling could not be identified. Female
      gender (OR = 2.8, 95% CI = 1.5-5.1), higher medication use (OR = 1.5, 95% CI =
      1.0-2.2) and depressive symptoms (OR = 1.9, 95% CI = 1.3-2.8) were independently
      associated with functional decline after falling. Depressive symptoms (OR = 2.0,
      95% CI = 1.2-3.3) and falls inside (OR = 2.6, 95% CI = 1.1-6.5) were risk factors
      for decline in social activities, while female gender (OR = 2.7, 95% CI = 1.1
      7.0) and depressive symptoms (OR = 1.9, 95% CI = 1.2-3.0) were risk factors for
      decline in physical activities after falling. CONCLUSIONS: almost 70% of the
      respondents suffered physical injury, almost one-quarter used health services and
      more than one-third suffered functional decline after falling. No risk factors
      were found for health service use needed after falling. Female gender, higher
      medication use, depressive symptoms and falls inside were risk factors for
      functional decline after falling.

PMID- 14695866
TI  - Clinical significance of cerebral white matter lesions in older Asians with
      suspected dementia.
AB  - BACKGROUND: cerebral white matter lesions are commonly seen on neuroimaging in
      older people and have been associated with clinical features such as gait
      abnormalities, urinary incontinence and depression. The significance of cerebral
      white matter lesions in older people with dementia remains uncertain. OBJECTIVES:
      to study the association between cerebral white matter lesions and the presence
      or absence of dementia in a group of elderly Asian patients; and to determine the
      clinical significance of cerebral white matter lesions in patients who are
      diagnosed to have dementia in terms of associated clinical features and the
      impact of cerebral white matter lesions on cognitive status. METHODS: for the
      first objective, the records of 141 older people of Asian ethnicity presenting to
      a memory clinic for the evaluation of suspected dementia were reviewed to compare
      the prevalence of cerebral white matter lesions in patients who did not fulfil
      the criteria for dementia, patients diagnosed to have Alzheimer's disease and
      patients diagnosed to have vascular dementia. For the second objective, 115 of
      these patients who were diagnosed to have dementia were studied to determine if
      demented patients with cerebral white matter lesions were more likely to have
      urinary incontinence, Parkinsonism, depression and greater severity of dementia.
      In addition, a comparison was made between demented patients with cerebral white
      matter lesions and those without cerebral white matter lesions in terms of
      psychometric assessment scores. RESULTS: cerebral white matter lesions were more
      common in Asian patients with vascular dementia. Demented patients with cerebral
      white matter lesions were also found to have more severe dementia and greater
      functional disability. CONCLUSION: cerebral white matter lesions are common, and
      are associated with greater functional disability in elderly Asian patients with
      dementia.

PMID- 14695867
TI  - Prevalence and prediction of unrecognised diabetes mellitus and impaired glucose
      tolerance following acute stroke.
AB  - BACKGROUND: diabetes mellitus not only increases the risk of ischaemic stroke two
      to four-fold but also adversely inXuences prognosis. The prevalence of
      recognised diabetes mellitus in acute stroke patients is between 8 and 20%, but
      between 6 and 42% of patients may have undiagnosed diabetes mellitus before
      presentation. Post-stroke hyperglycaemia is frequent and of limited diagnostic
      value and the oral glucose tolerance test assumes that the patient is clinically
      stable and eating normally. There is a need for a simple and reliable method to
      predict new diabetes mellitus in acute stroke patients. OBJECTIVES: to determine
      the prevalence of unrecognised diabetes mellitus and impaired glucose tolerance
      on hospital admission and 12 weeks later in acute stroke patients with post
      stroke hyperglycaemia > or = 6.1 mmol/l. To measure the accuracy of
      hyperglycaemia and elevated glycosylated haemoglobin concentration in predicting
      the presence of unrecognised diabetes mellitus at 12 weeks. DESIGN: acute (<24
      hours) stroke patients (cerebral infarction and primary intracerebral
      haemorrhage) with admission hyperglycaemia between 6.0 and 17 mmol/l and without
      a previous history of insulin-treated diabetes mellitus who were randomised into
      the Glucose Insulin in Stroke Trial between October 1997 and May 1999 were
      studied. The Glucose Insulin in Stroke Trial is a randomised controlled trial
      investigating the benefits of maintaining euglycaemia in acute stroke patients
      with mild to moderate hyperglycaemia. At 12 weeks, survivors underwent a 75 g
      oral glucose tolerance test. The positive predictive value and negative
      predictive value of admission plasma glucose > or = 6.1 mmol/l and elevated
      glycosylated haemoglobin concentration in predicting the presence of diabetes
      mellitus were used to estimate the prevalence of unrecognised diabetes mellitus
      in a consecutive series of 582 acute stroke admissions. RESULTS: 582 consecutive
      acute stroke patients were assessed for eligibility for the Glucose Insulin
      Stroke Trial, of whom 83 (14%) had recognised diabetes mellitus. One hundred and
      forty-two patients were randomised and 62 underwent a 3-month oral glucose
      tolerance test, of whom 26 (42%) had normal glucose tolerance, 23 (37%) had
      impaired glucose tolerance and 13 (21%) had diabetes mellitus. Admission plasma
      glucose > or = 6.1 mmol/l and glycosylated haemoglobin > or = 6.2% predicted the
      presence of previously unrecognised diabetes mellitus at 12 weeks with a positive
      predictive value of 80% and negative predictive value of 96%. The estimated
      prevalence of unrecognised diabetes mellitus in the total series of acute stroke
      admissions was 16-24%. CONCLUSIONS: one-third of all acute stroke patients may
      have diabetes mellitus. For patients presenting with post-stroke hyperglycaemia,
      impaired glucose tolerance or diabetes mellitus is present in two-thirds of
      survivors at 12 weeks. Admission plasma glucose > or = 6.1 mmol/l combined with
      glycosylated haemoglobin > or = 6.2% are good predictors of the presence of
      diabetes mellitus following stroke.

PMID- 14695868
TI  - Non-convulsive status epilepticus in elderly individuals: report of four
      representative cases.
AB  - OBJECTIVE: the purpose of this article is to describe the clinical and
      electroencephalographic features of four elderly patients diagnosed as having non
      convulsive status epilepticus. METHODS: four females ranging in age from 74 to 81
      years were admitted to our hospital because of confusion and altered mental
      state. We recognised four distinctive entities: i) Absence status in a patient
      with pre-existing idiopathic generalised epilepsy; ii) De novo absence status of
      late onset precipitated by benzodiazepine withdrawal; iii) Complex partial status
      epilepticus in a patient with a focal brain lesion; iv) Subtle generalised status
      epilepticus in a comatose subject representing the final phase of convulsive
      status epilepticus. CONCLUSIONS: the identification of non-convulsive status
      epilepticus may be particularly arduous in elderly subjects and, therefore, a
      high level of suspicion is essential to obtain an early diagnosis. An urgent
      electroencephalogram is considered as the method of choice in the diagnostic
      evaluation of non-convulsive status epilepticus. Finally, non-convulsive status
      epilepticus should be included among the causes of coma in older individuals.

PMID- 14695869
TI  - Small bowel obstruction from a dislodged feeding tube.
AB  - Elderly nursing home patients may suffer from inadequate oral nutritional intake
      for a variety of reasons. In some of them, nutritional status cannot be
      maintained without the use of enteral feeding. Nasogastric tube feeding is
      associated with significant patient discomfort, and may lead to significant
      complications. Thus, in those who require long-term enteral tube feeding, a
      gastrostomy tube may be necessary. Although surgical insertion may occasionally
      be required, percutaneous insertion with upper endoscopy assistance is usually
      safe and feasible. This case represents an unusual complication of such a
      gastrostomy tube, which draws attention to the need for appropriate care of these
      tubes.

PMID- 14695870
TI  - SARS - a geriatrician's perspective.

PMID- 14695871
TI  - The right medicine.

PMID- 14695872
TI  - Frailty is the main predictor of falls in elderly patients undergoing
      rehabilitation training.

PMID- 14695873
TI  - Prescribing indicators.

PMID- 14695874
TI  - Using prescribing indicators to measure the quality of prescribing to elderly
      medical in-patients.

PMID- 14695876
TI  - Where now with Do Not Attempt Resuscitation decisions?

PMID- 14695877
TI  - Prevention of malnutrition in older people during and after hospitalisation:
      results from a randomised controlled trial.

PMID- 14695884
TI  - Directed evolution of mammalian paraoxonases PON1 and PON3 for bacterial
      expression and catalytic specialization.
AB  - Serum paraoxonases (PONs) are a group of enzymes that play a key role in
      organophosphate (OP) detoxification and in prevention of atherosclerosis.
      However, their structure and mechanism of action are poorly understood. PONs seem
      like jacks-of-all-trades, acting on a very wide range of substrates, most of
      which are of no physiological relevance. Family shuffling and screening lead to
      the first PON variants that express in a soluble and active form in Escherichia
      coli. We describe variants with kinetic parameters similar to those reported for
      PONs purified from sera and others that show dramatically increased activities.
      In particular, we have evolved PON1 variants with OP-hydrolyzing activities 40
      fold higher than wild type and a specificity switch of >2,000-fold, producing
      PONs specialized for OP rather than ester hydrolysis. Analysis of the newly
      evolved variants provides insights into the evolutionary relationships between
      different family members.

PMID- 14695885
TI  - Essential requirement for Wnt signaling in proliferation of adult small intestine
      and colon revealed by adenoviral expression of Dickkopf-1.
AB  - Whereas the adult gastrointestinal epithelium undergoes tremendous self-renewal
      through active proliferation in crypt stem cell compartments, the responsible
      growth factors regulating this continuous proliferation have not been defined.
      The exploration of physiologic functions of Wnt proteins in adult organisms has
      been hampered by functional redundancy and the necessity for conditional
      inactivation strategies. Dickkopf-1 (Dkk1) is a potent secreted Wnt antagonist
      that interacts with Wnt coreceptors of the LRP family. To address the
      contribution of Wnt signaling to gastrointestinal epithelial proliferation,
      adenoviral expression of Dkk1 was used to achieve stringent, conditional, and
      reversible Wnt inhibition in adult animals. Adenovirus Dkk1 (Ad Dkk1) treatment
      of adult mice repressed expression of the Wnt target genes CD44 and EphB2 within
      2 days in both small intestine and colon, indicating an extremely broad role for
      Wnt signaling in the maintenance of adult gastrointestinal gene expression. In
      parallel, Ad Dkk1 markedly inhibited proliferation in small intestine and colon,
      accompanied by progressive architectural degeneration with the loss of crypts,
      villi, and glandular structure by 7 days. Whereas decreased Dkk1 expression at
      later time points (>10 days) was followed by crypt and villus regeneration, which
      was consistent with a reversible process, substantial mortality ensued from
      colitis and systemic infection. These results indicate the efficacy of systemic
      expression of secreted Wnt antagonists as a general strategy for conditional
      inactivation of Wnt signaling in adult organisms and illustrate a striking
      reliance on a single growth factor pathway for the maintenance of the
      architecture of the adult small intestine and colon.

PMID- 14695886
TI  - Hubble's diagram and cosmic expansion.
AB  - Edwin Hubble's classic article on the expanding universe appeared in PNAS in 1929
      [Hubble, E. P. (1929) Proc. Natl. Acad. Sci. USA 15, 168-173]. The chief result,
      that a galaxy's distance is proportional to its redshift, is so well known and so
      deeply embedded into the language of astronomy through the Hubble diagram, the
      Hubble constant, Hubble's Law, and the Hubble time, that the article itself is
      rarely referenced. Even though Hubble's distances have a large systematic error,
      Hubble's velocities come chiefly from Vesto Melvin Slipher, and the
      interpretation in terms of the de Sitter effect is out of the mainstream of
      modern cosmology, this article opened the way to investigation of the expanding,
      evolving, and accelerating universe that engages today's burgeoning field of
      cosmology.

PMID- 14695887
TI  - Transcriptional signature of histone deacetylase inhibition in multiple myeloma:
      biological and clinical implications.
AB  - Histone deacetylases (HDACs) affect cell growth at the transcriptional level by
      regulating the acetylation status of nucleosomal histones. HDAC inhibition
      induces differentiation and/or apoptosis in transformed cells. We recently showed
      that HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA), potently
      induce apoptosis of human multiple myeloma (MM) cells. In this study, we focused
      on MM as a model to study the transcriptional profile of HDAC inhibitor treatment
      on tumor cells and to address their pathophysiological implications with
      confirmatory mechanistic and functional assays. We found that MM cells are
      irreversibly committed to cell death within few hours of incubation with SAHA.
      The hallmark molecular profile of MM cells before their commitment to SAHA
      induced cell death is a constellation of antiproliferative and/or proapoptotic
      molecular events, including down-regulation of transcripts for members of the
      insulin-like growth factor (IGF)/IGF-1 receptor (IGF-1R) and IL-6 receptor (IL
      6R) signaling cascades, antiapoptotic molecules (e.g., caspase inhibitors),
      oncogenic kinases, DNA synthesis/repair enzymes, and transcription factors (e.g.,
      XBP-1, E2F-1) implicated in MM pathophysiology. Importantly, SAHA treatment
      suppresses the activity of the proteasome and expression of its subunits, and
      enhances MM cell sensitivity to proteasome inhibition by bortezomib (PS-341).
      SAHA also enhances the anti-MM activity of other proapoptotic agents, including
      dexamethasone, cytotoxic chemotherapy, and thalidomide analogs. These findings
      highlight the pleiotropic antitumor effects of HDAC inhibition, and provide the
      framework for future clinical applications of SAHA to improve patient outcome in
      MM.

PMID- 14695888
TI  - Intracellular calmodulin availability accessed with two-photon cross-correlation.
AB  - The availability and interactions of signaling proteins are tightly regulated in
      time and space to produce specific and localized effects. For calmodulin (CaM), a
      key transducer of intracellular Ca(2+) signaling, binding to its variety of
      targets initiates signaling cascades and regulates its subcellular localization,
      thereby making it unavailable for subsequent binding interactions. Among CaM's
      numerous targets, Ca(2+)/CaM-dependent protein kinase II is one of the most
      striking due to its unique ability to increase its affinity for CaM by
      autophosphorylation and to translocate when bound to Ca(2+)/CaM. Two-photon
      fluorescence correlation spectroscopy and cross-correlation spectroscopy were
      utilized to compare mobility and molecular interactions between CaM and
      Ca(2+)/CaM-dependent protein kinase II in solution and in living cells. These
      techniques revealed that CaM availability in cells could be altered by a change
      in intracellular conditions. Two-photon fluorescence cross-correlation
      spectroscopy exemplifies a generally applicable approach for studying protein
      protein interactions in living cells that allows access to the behavior of
      signaling molecules within their native environment to probe for heterogeneities
      in signaling pathways in different cellular compartments.

PMID- 14695889
TI  - Reversing established sepsis with antagonists of endogenous high-mobility group
      box 1.
AB  - Despite significant advances in intensive care therapy and antibiotics, severe
      sepsis accounts for 9% of all deaths in the United States annually. The
      pathological sequelae of sepsis are characterized by a systemic inflammatory
      response, but experimental therapeutics that target specific early inflammatory
      mediators [tumor necrosis factor (TNF) and IL-1beta] have not proven efficacious
      in the clinic. We recently identified high mobility group box 1 (HMGB1) as a late
      mediator of endotoxin-induced lethality that exhibits significantly delayed
      kinetics relative to TNF and IL-1beta. Here, we report that serum HMGB1 levels
      are increased significantly in a standardized model of murine sepsis, beginning
      18 h after surgical induction of peritonitis. Specific inhibition of HMGB1
      activity [with either anti-HMGB1 antibody (600 microg per mouse) or the DNA
      binding A box (600 microg per mouse)] beginning as late as 24 h after surgical
      induction of peritonitis significantly increased survival (nonimmune IgG-treated
      controls = 28% vs. anti-HMGB1 antibody group = 72%, P < 0.03; GST control protein
      = 28% vs. A box = 68%, P < 0.03). Animals treated with either HMGB1 antagonist
      were protected against the development of organ injury, as evidenced by improved
      levels of serum creatinine and blood urea nitrogen. These observations
      demonstrate that specific inhibition of endogenous HMGB1 therapeutically reverses
      lethality of established sepsis indicating that HMGB1 inhibitors can be
      administered in a clinically relevant time frame.

PMID- 14695890
TI  - Latent infection membrane protein transmembrane FWLY is critical for
      intermolecular interaction, raft localization, and signaling.
AB  - Relatively little is known about the biochemical mechanisms through which the
      Epstein-Barr virus latent infection integral membrane protein 1 (LMP1)
      transmembrane domains cause constitutive LMP1 aggregation and continuous
      cytoplasmic C terminus-mediated signal transduction. We now evaluate the role of
      the three consecutive LMP1 hydrophobic transmembrane pairs, transmembrane domains
      (TM)1-2, TM3-4, and TM5-6, in intermolecular aggregation and NF-kappaB
      activation. LMP1TM1-2 enabled approximately 40% of wild-type LMP1 cytoplasmic
      domain-mediated NF-kappaB activation, whereas TM3-4 or TM5-6 assayed in parallel
      had almost no effect independent of LMP1TM1-2. Alanine mutagenesis of conserved
      residues in LMP1TM1-2 identified FWLY(38-41) to be critical for LMP1TM1-2
      intermolecular association with LMP1TM3-6. Further, in contrast to wild-type
      LMP1, LMP1 with FWLY(38-41) mutated to AALA(38-41) did not (i). significantly
      partition to lipid Rafts or Barges and effectively intermolecularly associate,
      (ii). enable cytoplasmic C terminus engagement of tumor necrosis factor receptor
      associated factor 3, (iii). activate NF-kappaB, and thereby (iv). induce tumor
      necrosis factor receptor-associated factor 1 expression. Other LMP1
      intermolecular associations were observed that involved LMP1TM1-2/LMP1TM1-2 or
      LMP1TM3-4/LMP1TM3-6 interactions; these probably also contribute to LMP1
      aggregation. Because FWLY(38-41) was essential for LMP1-mediated signal
      transduction, and LMP1 activation of NF-kappaB is essential for proliferating B
      lymphocyte survival, inhibition of LMP1FWLY(41)-mediated LMP1/LMP1 intermolecular
      interactions is an attractive therapeutic target.

PMID- 14695891
TI  - An egalitarian network model for the emergence of simple and complex cells in
      visual cortex.
AB  - We explain how simple and complex cells arise in a large-scale neuronal network
      model of the primary visual cortex of the macaque. Our model consists of
      approximately 4000 integrate-and-fire, conductance-based point neurons,
      representing the cells in a small, 1-mm(2) patch of an input layer of the primary
      visual cortex. In the model the local connections are isotropic and nonspecific,
      and convergent input from the lateral geniculate nucleus confers cortical cells
      with orientation and spatial phase preference. The balance between lateral
      connections and lateral geniculate nucleus drive determines whether individual
      neurons in this recurrent circuit are simple or complex. The model reproduces
      qualitatively the experimentally observed distributions of both extracellular and
      intracellular measures of simple and complex response.

PMID- 14695892
TI  - Biography of Constance L Cepko.

PMID- 14695893
TI  - Methylation and epigenetic fidelity.

PMID- 14695894
TI  - Shock-induced minerals in meteorite provide prospecting tools for mineral
      physics.

PMID- 14695895
TI  - Alcohol and inhibitory receptors: unexpected specificity from a nonspecific drug.

PMID- 14695896
TI  - Physical and functional interaction of androgen receptor with calmodulin in
      prostate cancer cells.
AB  - Ca(2+) and calmodulin (CaM) play a critical role in proliferation and viability
      of a wide variety of cells, including prostate cancer cells. We examined two
      prostate cancer cell lines, androgen-sensitive LNCaP and androgen-independent PC
      3. Proliferation of LNCaP cells was six to eight times more sensitive to the
      inhibitory effect of the CaM antagonist N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfonamide hydrochloride (W-7) than were PC-3 cells. Because LNCaP
      cell proliferation is sensitive to stimulation by androgen, we assessed the
      physical and functional interaction between androgen receptor (AR) and CaM. We
      observed tight binding of AR to CaM when LNCaP cell extracts were subjected to
      CaM-affinity column chromatography. AR binding to CaM was Ca(2+)-dependent and
      was inhibited by pretreatment of the cell extracts with W-7. Using
      immunofluorescence staining and confocal microscopy, we demonstrated
      colocalization of AR and CaM in the nucleus of LNCaP cells. Furthermore, the
      functional relevance of AR-CaM interactions in intact cells was revealed by the
      observation that W-7 was as effective as Casodex, an antiandrogen, in blocking AR
      regulated expression of prostate-specific antigen in LNCaP cells. AR seems to
      interact with CaM directly because purified human AR could bind to CaM-agarose,
      and CaM could be detected in AR-immunoprecipitate prepared from purified soluble
      proteins. These studies provide direct evidence for physical and functional
      interaction between AR and CaM and suggest the potential usefulness of CaM
      antagonists in blocking AR activity in prostate cancer.

PMID- 14695897
TI  - Variable ecological effects of hurricanes: the importance of seasonal timing for
      survival of lizards on Bahamian islands.
AB  - Two recent hurricanes passed directly over the northern Bahamas 2 years apart,
      allowing a comparison of their effects on lizard populations inhabiting exactly
      the same islands. The hurricanes differed in two ways: one struck during the
      reproductive season and was relatively severe; the other struck after most
      reproduction had taken place and was milder. The late-season hurricane produced a
      significant relation between population reduction and lowness of the island that
      lasted at least through two seasons; the earlier hurricane produced no such
      relationship. The late-season hurricane wiped out populations of lizards on two
      islands (two of the three lowest) that the earlier hurricane failed to
      exterminate even though it was stronger. We relate these effects to the fact that
      the study lizards regenerated from the earlier hurricane only via the egg stage,
      whereas eggs were unavailable when the later storm struck and regeneration was
      via hatched lizards. We discriminate and illustrate four kinds of hurricanes,
      cross-classified by two contrasts: earlier vs. later and stronger vs. weaker. A
      later, stronger hurricane completely exterminated lizard populations at a second
      Bahamian site, whereas an earlier, weaker hurricane had no detectable effect at a
      third Bahamian site. We suggest that, in addition to severity, the timing of a
      hurricane as it coincides with reproductive scheduling or other phenological
      aspects may determine the magnitude of its effect on a variety of organisms.

PMID- 14695898
TI  - Context-dependent regulation of GATA-1 by friend of GATA-1.
AB  - The transcription factor GATA-1 and its cofactor, friend of GATA-1 (FOG-1), are
      essential for normal erythroid development. FOG-1 physically interacts with GATA
      1 to augment or inhibit its activity. The mechanisms by which FOG-1 regulates
      GATA-1 function are unknown. By using an assay that is based on the phenotypic
      rescue of a GATA-1-null erythroid cell line, we found that a conditional form of
      GATA-1 (GATA-1-ER) strongly induced histone acetylation at the beta-major globin
      promoter in vivo, consistent with previous results. In contrast, GATA-1 bearing a
      point mutation that impairs FOG-1 binding [GATA-1(V205M)-ER] failed to induce
      high levels of histone acetylation at this site. However, at DNase I
      hypersensitive site (HS)3 of the beta-globin locus control region, GATA-1-induced
      histone acetylation was FOG-1-independent. Because the V205M mutation does not
      disrupt GATA-1 binding to DNA templates in vitro, we were surprised to find that
      in vivo GATA-1(V205M)-ER fails to bind the beta-globin promoter. However, at HS3,
      DNA binding by GATA-1 was FOG-1-independent, thus correlating histone acetylation
      with GATA-1 occupancy. Examination of additional GATA-1-dependent regulatory
      elements showed that the interaction with FOG-1 is required for GATA-1 occupancy
      at select sites, such as HS2, but is dispensable at others, including the FOG-1
      independent GATA-1 target gene EKLF. Remarkably, at the GATA-2 gene, which is
      repressed by GATA-1, interaction with FOG-1 was dispensable for GATA-1 occupancy
      and was required for transcriptional inhibition and histone deacetylation. These
      results indicate that FOG-1 employs distinct mechanisms when cooperating with
      GATA-1 during transcriptional activation and repression.

PMID- 14695899
TI  - A polyketide synthase catalyzes the last condensation step of mycolic acid
      biosynthesis in mycobacteria and related organisms.
AB  - Mycolic acids are major and specific constituents of the cell envelope of
      Corynebacterineae, a suborder of bacterial species including several important
      human pathogens such as Mycobacterium tuberculosis, Mycobacterium leprae, or
      Corynebacterium diphtheriae. These long-chain fatty acids are involved in the
      unusual architecture and impermeability of the cell envelope of these bacteria.
      The condensase, the enzyme responsible for the final condensation step in mycolic
      acid biosynthesis, has remained an enigma for decades. By in silico analysis of
      various mycobacterial genomes, we identified a candidate enzyme, Pks13, that
      contains the four catalytic domains required for the condensation reaction.
      Orthologs of this enzyme were found in other Corynebacterineae species. A
      Corynebacterium glutamicum strain with a deletion in the pks13 gene was shown to
      be deficient in mycolic acid production whereas it was able to produce the fatty
      acids precursors. This mutant strain displayed an altered cell envelope
      structure. We showed that the pks13 gene was essential for the survival of
      Mycobacterium smegmatis. A conditional M. smegmatis mutant carrying its only copy
      of pks13 on a thermosensitive plasmid exhibited mycolic acid biosynthesis defect
      if grown at nonpermissive temperature. These results indicate that Pks13 is the
      condensase, a promising target for the development of new antimicrobial drugs
      against Corynebacterineae.

PMID- 14695900
TI  - Stimulatory and inhibitory protein kinase C consensus sequences regulate the
      cystic fibrosis transmembrane conductance regulator.
AB  - Protein kinase C (PKC) phosphorylation stimulates the cystic fibrosis
      transmembrane conductance regulator (CFTR) channel and enhances its activation by
      protein kinase A (PKA) through mechanisms that remain poorly understood. We have
      examined the effects of mutating consensus sequences for PKC phosphorylation and
      report here evidence for both stimulatory and inhibitory sites. Sequences were
      mutated in subsets and the mutants characterized by patch clamping. Activation of
      a 4CA mutant (S707A/S790A/T791A/S809A) by PKA was similar to that of wild-type
      CFTR and was enhanced by PKC, whereas responses of 3CA (T582A/T604A/S641A) and
      2CA (T682A/S686A) channels to PKA were both drastically reduced (>90%). When each
      mutation in the 3CA and 2CA constructs was studied individually in a wild-type
      background, T582, T604, and S686 were found to be essential for PKA activation.
      Responses were restored when these three residues were reintroduced
      simultaneously into a 9CA mutant lacking all nine PKC consensus sequences (R6CA
      revertant); however, PKC phosphorylation was not required for this rescue.
      Nevertheless, two of the sites (T604 and S686) were phosphorylated in vitro, and
      PKC alone partially activated wild-type CFTR, the 4CA mutant, and the point
      mutants T582A and T604A, but not S686A channels, indicating that PKC does act at
      S686. The region encompassing S641 and T682 is inhibitory, because S641A enhanced
      activation by PKA, and T682A channels had 4-fold larger responses to PKC compared
      to wild-type channels. These results identify functionally important PKC
      consensus sequences on CFTR and will facilitate studies of its convergent
      regulation by PKC and PKA.

PMID- 14695901
TI  - The power and the limitations of cross-species protein identification by mass
      spectrometry-driven sequence similarity searches.
AB  - Mass spectrometry-driven BLAST (MS BLAST) is a database search protocol for
      identifying unknown proteins by sequence similarity to homologous proteins
      available in a database. MS BLAST utilizes redundant, degenerate, and partially
      inaccurate peptide sequence data obtained by de novo interpretation of tandem
      mass spectra and has become a powerful tool in functional proteomic research.
      Using computational modeling, we evaluated the potential of MS BLAST for proteome
      wide identification of unknown proteins. We determined how the success rate of
      protein identification depends on the full-length sequence identity between the
      queried protein and its closest homologue in a database. We also estimated
      phylogenetic distances between organisms under study and related reference
      organisms with completely sequenced genomes that allow substantial coverage of
      unknown proteomes.

PMID- 14695902
TI  - Input signals to the plant circadian clock.
AB  - Eukaryotes and some prokaryotes have adapted to the 24 h day/night cycle by
      evolving circadian clocks, which now control very many aspects of metabolism,
      physiology and behaviour. Circadian clocks in plants are entrained by light and
      temperature signals from the environment. The relative timing of internal and
      external events depends upon a complex interplay of interacting rhythmic controls
      and environmental signals, including changes in the period of the clock. Several
      of the phytochrome and cryptochrome photoreceptors responsible have been
      identified. This review concentrates on the resulting patterns of entrainment and
      on the multiple proposed mechanisms of light input to the circadian oscillator
      components.

PMID- 14695903
TI  - Estrogen is not directly required for oocyte developmental competence.
AB  - Oocyte maturation and ovulation require a coordinated interaction between
      gonadotrophs, steroid hormones, and growth factors. The extent to which estrogen
      is required in this process, however, remains unclear. To better understand the
      role of estrogen in maintaining developmental competence of mammalian oocytes, we
      studied the Aromatase knockout (ArKO) mouse, which has been genetically
      engineered to be incapable of synthesizing endogenous estrogen. Previous studies
      have established that ArKO female mice are anovulatory with ovaries that
      progressively degenerate, developing hemorrhagic cystic follicles. In young ArKO
      females, however, apparently healthy follicles and oocytes have been observed. We
      investigated if these oocytes could be induced to ovulate, then mature,
      fertilize, and develop in vitro. Following a standard superovulation protocol,
      ArKO oocytes did not ovulate. When recovered manually from the ovary, however,
      ArKO oocytes successfully progressed through in vitro maturation, fertilization,
      and development to the blastocyst stage at the same rate as wild-type and
      heterozygote littermates. Therefore, it appears that estrogen is not required for
      the production and growth of oocytes capable of maturation and complete
      preimplantation development but is required for continued follicle growth and
      feedback regulation of ovulation.

PMID- 14695904
TI  - Effects of prolactin on the luteinizing hormone response to gonadotropin-
      releasing hormone in primary pituitary cell cultures during the ovine annual
      reproductive cycle.
AB  - In the sheep pituitary, the localization of prolactin (PRL) receptors in
      gonadotrophs and the existence of gonadotroph-lactotroph associations have
      provided morphological evidence for possible direct effects of PRL on
      gonadotropin secretion. Here, we investigated whether PRL can readily modify the
      LH response to GnRH throughout the ovine annual reproductive cycle. Cell
      populations were obtained from sheep pituitaries during the breeding season (BS)
      and the nonbreeding season (NBS), plated to monolayer cultures for 7 days, and
      assigned to receive one of the following treatments: 1) nil (control), 2) acute
      (90- min) bromocriptine (ABr), 3) chronic (7-day) bromocriptine (CBr), 4) ABr and
      PRL, 5) CBr and PRL, 6) PRL alone, or 7) thyrotropin-releasing hormone. Cells
      were treated as described above, with the aim of decreasing or increasing the
      concentrations of PRL in the culture, and simultaneously treated with GnRH for 90
      min. The LH concentrations in the medium were then determined by RIA. GnRH
      stimulated LH in a dose-dependent manner during both stages of the annual
      reproductive cycle. During the NBS, single treatments did not significantly
      affect the LH response to GnRH. However, when PRL was combined with
      bromocriptine, either acutely or chronically, GnRH failed to stimulate LH release
      at all doses tested (P < 0.01). In contrast, during the BS, the LH response to
      GnRH was not affected by any of the experimental treatments. These results reveal
      no apparent effects of PRL alone, but an interaction between PRL and dopamine in
      the regulation of LH secretion within the pituitary gland, and a seasonal
      modulation of this mechanism.

PMID- 14695905
TI  - Leukemia inhibitory factor antisense oligonucleotide inhibits the development of
      murine embryos at preimplantation stages.
AB  - Leukemia inhibitory factor (LIF) is an essential factor for implantation and
      establishment of pregnancy. However, its role in the development of
      preimplantation embryos remains controversial. In this study, changes in
      preimplantation embryos were determined after microinjection of LIF antisense
      oligonucleotide at the two-pronucleus stage. Although no significant differences
      were found in the percentages between the untreated group and the 0.25-fmol
      treated group, the 0.5- or 1.0-fmol-treated groups had significantly lower
      percentages of embryos developed to the morula or blastocyst stage and the 2.0
      fmol-treated group had significantly lower percentages of embryos developed to
      the four-cell, morula, or blastocyst stage. No embryos developed to the four-cell
      stage in the 4.0-fmol-treated group. Moreover, there was a decreasing trend in
      the levels of LIF immunoactivity with the increasing amount of LIF antisense
      oligonucleotide injected. The diameter of blastocysts in the 2.0-fmol-treated
      group was significantly smaller than that in the untreated group. The blastocysts
      in this group had significantly lower numbers of blastomeres and cells in the
      inner cell mass (ICM) or trophectoderm (TE) and ICM:TE ratio. The 1.0- or 2.0
      fmol-treated groups had significantly lower implantation rates than their
      corresponding control groups. In the 2.0-fmol groups with supplementing exogenous
      LIF, significantly lower percentages were also observed in the four-cell, morula,
      and blastocyst stages. However, blastocysts treated with 50 ng/ml LIF had a
      significantly higher percentage than those in the LIF gene-impaired group without
      LIF supplement. These results indicate that LIF is a critical factor for the
      normal development of embryos at the preimplantation stages.

PMID- 14695906
TI  - Key role for cyclin-dependent kinases in the first and second meiotic divisions
      of rat spermatocytes.
AB  - In all systems examined so far, the G2/M phase transition is controlled by the M
      phase promoting factor (MPF), a complex of cdc2 (CDK1) and cyclin B1. Histone H1
      kinase activity and MPF components are present in pachytene spermatocytes (PS).
      However, it has not been demonstrated yet that direct inhibition of MPF activity
      prevents the G2/M transition in these cells. When roscovitine, a potent inhibitor
      of CDK1, CDK2, and CDK5 activities, was added to cocultures of PS with Sertoli
      cells, the number of both secondary spermatocytes and round spermatids formed
      were lower than in control cultures, despite similar cell viability. This effect
      of roscovitine was reversible, did not involve the Sertoli cells, and was
      dependent on the concentration of the inhibitor. Roscovitine did not modify the
      amount of MPF in these germ cells but inhibited the CDK1- or CDK2-associated
      histone H1 kinase activity of PS. Hence a functional relationship between cyclin
      dependent kinase activity and the spontaneous processing of the first meiotic
      division and, for the first time, of the second meiotic division of male germ
      cells is shown.

PMID- 14695907
TI  - Maternal growth hormone treatment from day 35 to 80 of gestation alters nutrient
      partitioning in favor of uteroplacental growth in the overnourished adolescent
      sheep.
AB  - Overnourishing the pregnant adolescent ewe promotes maternal tissue synthesis at
      the expense of placental growth and leads to a major reduction in lamb birth
      weight at term. Growth hormone (GH) secretion is attenuated in these
      overnourished dams and the maternal somatotrophic axis may play a key role in
      coordinating nutrient usage in the pregnant adolescent. Thus we investigated
      whether increasing maternal GH during the period of rapid placental proliferation
      alters nutrient partitioning between the maternal, placental, and fetal tissues
      as assessed at Day 81 of gestation. Adolescent recipient ewes were implanted with
      singleton embryos, derived from superovulated dams and a single sire on Day 4
      postestrus. Thereafter, the ewes were offered either a high (H) or moderate
      intake (M) of the same complete diet. From Day 35 to 80 of gestation, ewes were
      either injected twice daily (s.c. at 0800 and 1800 h) with recombinant bovine GH
      (bGH, 0.14 mg/kg live weight/day) or remained untreated (n = 8 ewes per group).
      Maternal concentrations of GH, insulin, insulin-like growth factor (IGF-1),
      glucose, and non-esterified fatty acids (NEFAs) were higher, and leptin secretion
      lower, in bGH-treated dams from both nutritional groups. Maternal body weight
      gain was higher in H versus M groups and was independent of bGH treatment.
      Treatment with bGH reduced relative perirenal and carcass fat deposition and
      increased carcass protein content in both H and M dams. Uteroplacental mass
      (uterus + placentomes + fetal membranes) averaged 1099, 1069, 1112, and 1754 g in
      M, H, M+GH, and H+GH groups. This significant increase in uteroplacental
      development in the H+GH group was associated with higher fetal kidney and liver
      weights and elevated fetal insulin, glucose, and lactate concentrations.
      Treatment with bGH also induced polyhydramnios in the H group. The transplacental
      glucose gradient was increased twofold in the H+GH group but placental GLUT- 1
      and GLUT-3 expression was unaffected. In conclusion, administration of GH during
      the period of rapid placental proliferation alters endocrine status and thus
      nutrient partitioning in the overnourished adolescent dam in favor of
      uteroplacental and fetal growth. It remains to be established whether these
      effects are due wholly to alterations in maternal metabolism or if they also
      reflect an effect of bGH and/or the IGF system at the level of the uteroplacenta.

PMID- 14695908
TI  - Blastocyst formation rates in vivo and in vitro of in vitro-matured equine
      oocytes fertilized by intracytoplasmic sperm injection.
AB  - This study was conducted to evaluate in vivo and in vitro development of in vitro
      matured equine oocytes fertilized by intracytoplasmic sperm injection. Oocytes
      were collected from slaughterhouse-derived ovaries, matured in vitro, and
      injected with frozen-thawed stallion sperm. In vivo development was assessed
      after transfer of injected oocytes to the oviducts of recipient mares. Mares were
      killed 7.5-8.5 days after transfer and the uterus and oviducts flushed for embryo
      recovery. Of 132 injected oocytes transferred, 69 (52%) were recovered; of these,
      25 (36%) were blastocysts with a blastocoele and capsule. In vitro development
      was assessed in three culture systems. Culture of zygotes in modified Chatot,
      Ziomek, Bavister medium with BSA containing either 5.5 mM glucose for 7.5 days or
      0.55 mM glucose for 3 days, followed by 3 mM glucose for 2 days, then 4.3 mM
      glucose for 2.5 days, did not result in blastocyst formation. Culture of zygotes
      in Dulbecco modified Eagle medium (DMEM)/F-12 with 10% fetal bovine serum with
      and without coculture with equine oviductal epithelial explants yielded 16% and
      15% blastocyst development, respectively. Development to blastocyst was
      significantly lower in G1.3/2.3/BSA than in DMEM/F-12/BSA or in either medium
      with 10% added serum (2% vs. 18%, 18% or 20%; P < 0.05), suggesting that
      requirements for equine embryo development differ from those for other species.
      These results indicate that in vitro-matured equine oocytes are sufficiently
      competent to form 36% blastocysts in an optimal environment (in vivo). While we
      identified an in vitro culture system that provided repeatable blastocyst
      development without coculture, this yielded only half the rate of development
      achieved in vivo.

PMID- 14695909
TI  - Stage-dependent effects of oocytes and growth differentiation factor 9 on mouse
      granulosa cell development: advance programming and subsequent control of the
      transition from preantral secondary follicles to early antral tertiary follicles.
AB  - The development of an ovarian follicle requires a complex set of reciprocal
      interactions between the oocyte and granulosa cells in order for both types of
      cells to develop properly. These interactions are largely orchestrated by the
      oocyte via paracrine factors such as growth differentiation factor 9 (GDF9). To
      examine these interactions further, a study was conducted of the effects of
      oocytes at different stages of development on proteins synthesized by mouse
      granulosa cells during the transition of granulosa cells (GCs) from preantral,
      secondary (2 degrees ) follicles (2 degrees GCs) to mural granulosa cells (3
      degrees GCs) of antral tertiary (3 degrees ) follicles. The ability of
      recombinant GDF9 to mimic the effects of oocytes was also determined. Effects
      were evaluated by high- resolution, two-dimensional protein gel electrophoresis
      coupled to computer-assisted, quantitative gel image analysis. Coculture of the 2
      degrees GCs with growing oocytes (GOs) from 2 degrees follicles brought about
      many of the changes in granulosa cell phenotype associated with the 2 degrees to
      3 degrees follicle transition. GDF9 likewise brought about many of these changes,
      but only a subset of GDF9-affected protein spots were also affected by coculture
      with GOs. Coculture of 2 degrees GCs with the nearly fully grown oocytes (FGOs)
      from 3 degrees follicles had a reduced effect on 2 degrees GC phenotype, in
      comparison with coculture with GOs. For some proteins, oocyte coculture or GDF9
      treatment appeared to have opposite effects on 2 degrees GCs and 3 degrees GCs.
      Additional effects of GDF9 and oocytes were seen in cultures of 2 degrees GCs for
      proteins other than those that differed between untreated control 2 degrees and 3
      degrees GCs. These results indicate that GOs and GDF9 can each induce 2 degrees
      GCs to shift their phenotype toward that of 3 degrees GCs. The ability of the
      oocyte to produce this effect is diminished with oocyte development. The
      transition in the GC phenotype promoted by oocytes appears stable because
      differences in 2 degrees GCs promoted by oocytes and GDF9 were observed in
      untreated 3 degrees GCs. We conclude that the influence of the oocyte on GCs
      changes with the progression of their development, and so too does the response
      of the GCs to the oocyte. Moreover, by acting on the 2 degrees GCs, GOs are able
      to influence stably the phenotype of 3 degrees GCs. Thus, at or near the 2
      degrees to 3 degrees follicle transition, signals from the growing oocyte
      contribute to the development of the mural GC phenotype.

PMID- 14695910
TI  - Commitment of fetal male germ cells to spermatogonial stem cells during mouse
      embryonic development.
AB  - The continuous production of mammalian sperm is maintained by the proliferation
      and differentiation of spermatogonial stem cells that originate from primordial
      germ cells (PGCs) in the early embryo. Although spermatogonial stem cells arise
      from PGCs, it is not clear whether fetal male germ cells function as
      spermatogonial stem cells able to produce functional sperm. In the present study,
      we examined the timing and mechanisms of the commitment of fetal germ cells to
      differentiate into spermatogonial stem cells by transplantation techniques.
      Transplantation of fetal germ cells into the seminiferous tubules of adult testis
      showed that donor germ cells, at 14.5 days postcoitum (dpc), were able to
      initiate spermatogenesis in the adult recipient seminiferous tubules, whereas no
      germ cell differentiation was observed in the transplantation of 12.5-dpc germ
      cells. These results indicate that the commitment of fetal germ cells to
      differentiate into spermatogonial stem cells initiates between embryonic days
      12.5 and 14.5. Furthermore, the results suggest the importance of the interaction
      between germ cells and somatic cells in the determination of fetal germ cell
      differentiation into spermatogonial stem cells, as normal spermatogenesis was
      observed when a 12.5-dpc whole gonad was transplanted into adult recipient
      testis. In addition, sperm obtained from the 12.5- dpc male gonadal explant had
      the ability to develop normally if injected into the cytoplasm of oocytes,
      indicating that normal development of fetal germ cells in fetal gonadal explant
      occurred in the adult testicular environment.

PMID- 14695911
TI  - Control of mouse hils1 gene expression during spermatogenesis: identification of
      regulatory element by transgenic mouse.
AB  - Histone H1-like protein in spermatids 1 (Hils1) is a testis- specific histone H1
      like protein exclusively expressed in haploid spermatids and should be involved
      in chromatin remodeling during mouse spermatogenesis. Spatial and temporal
      regulation of the hils1 gene expression would be critical for the formation of
      functional sperm, controlled at both transcriptional and translational levels.
      Previously, we reported that transcripts of the hils1 gene are exclusively
      expressed in mouse testis from 23 days of age whereas the Hils1 protein is not
      detected until 28 days of age, suggesting that hils1 is a member of a class of
      translationally regulated genes. By analyzing transgenic mice, we could
      demonstrate that 318-base pair (bp) 5'-proximal region corresponding to the first
      70-bp proximal TATA-less promoter, and 248 bp of 5'-untranslated region is
      sufficient to confer testis- and spermatid-specific transcription as well as
      posttranscriptional control of the mouse hils1 gene in vivo.

PMID- 14695912
TI  - The novel dominant mutation Dspd leads to a severe spermiogenesis defect in mice.
AB  - Spermiogenesis is a complex process that is regulated by a plethora of genes and
      interactions between germ and somatic cells. Here we report a novel mutant mouse
      strain that carries a transgene insertional/translocational mutation and exhibits
      dominant male sterility. We named the mutation dominant spermiogenesis defect
      (Dspd). In the testes of Dspd mutant mice, spermatids detached from the
      seminiferous epithelium at different steps of the differentiation process before
      the completion of spermiogenesis. Microinsemination using spermatids collected
      from the mutant testes resulted in the birth of normal offspring. These
      observations indicate that the major cause of Dspd infertility is (are) a
      defect(s) in the Sertoli cell-spermatid interaction or communication in the
      seminiferous tubules. Fluorescent in situ hybridization (FISH) analysis revealed
      a translocation between chromosomes 7F and 14C at the transgene insertion site.
      The deletion of a genomic region of chromosome 7F greater than 1 megabase and
      containing at least six genes (Cttn, Fadd, Fgf3, Fgf4, Fgf15, and Ccnd1) was
      associated with the translocation. Cttn encodes the actin-binding protein
      cortactin. Immunohistochemical analysis revealed localization of cortactin beside
      elongated spermatids in wild-type testes; abnormality of cortactin localization
      was found in mutant testes. These data suggest an important role of cortactin in
      Sertoli cell-spermatid interactions and in the Dspd phenotype.

PMID- 14695913
TI  - Aurora-A is a critical regulator of microtubule assembly and nuclear activity in
      mouse oocytes, fertilized eggs, and early embryos.
AB  - Aurora-A is a serine/threonine protein kinase that plays a role in cell-cycle
      regulation. The activity of this kinase has been shown to be required for
      regulating multiple stages of mitotic progression in somatic cells. In this
      study, the changes in aurora-;A expression were revealed in mouse oocytes using
      Western blotting. The subcellular localization of aurora-A during oocyte meiotic
      maturation, fertilization, and early cleavages as well as after antibody
      microinjection or microtubule assembly perturbance was studied with confocal
      microscopy. The quantity of aurora-A protein was high in the germinal vesicle
      (GV) and metaphase II (MII) oocytes and remained stable during other meiotic
      maturation stages. Aurora-A concentrated in the GV before meiosis resumption, in
      the pronuclei of fertilized eggs, and in the nuclei of early embryo blastomeres.
      Aurora-A was localized to the spindle poles of the meiotic spindle from the
      metaphase I (MI) stage to metaphase II stage. During early embryo development,
      aurora-A was found in association with the mitotic spindle poles. Aurora-A was
      not found in the spindle region when colchicine or staurosporine was used to
      inhibit microtubule organization, while it accumulated as several dots in the
      cytoplasm after taxol treatment. Aurora-A antibody microinjection decreased the
      rate of germinal vesicle breakdown (GVBD) and distorted MI spindle organization.
      Our results indicate that aurora-A is a critical regulator of cell-cycle
      progression and microtubule organization during mouse oocyte meiotic maturation,
      fertilization, and early embryo cleavage.

PMID- 14695914
TI  - Papers from the Third Conference of the International Coenzyme Q10 Association.
      London, United Kingdom. November 22-24, 2002.

PMID- 14695915
TI  - Structural and functional organization of Complex I in the mitochondrial
      respiratory chain.
AB  - Metabolic flux control analysis of NADH oxidation in bovine heart
      submitochondrial particles revealed high flux control coefficients for both
      Complex I and Complex III, suggesting that the two enzymes are functionally
      associated as a single enzyme, with channelling of the common substrate, Coenzyme
      Q. This is in contrast with the more accepted view of a mobile diffusable
      Coenzyme Q pool between these enzymes. Dilution with phospholipids of a
      mitochondrial fraction enriched in Complexes I and III, with consequent increased
      theoretical distance between complexes, determines adherence to pool behavior for
      Coenzyme Q, but only at dilution higher than 1:5 (protein:phospholipids),
      whereas, at lower phospholipid content, the turnover of NADH cytochrome c
      reductase is higher than expected by the pool equation.

PMID- 14695916
TI  - Regulation of coenzyme Q biosynthesis and breakdown.
AB  - All animal cells synthesize sufficient amounts of coenzyme Q (CoQ) and the cells
      also possess the capacity to metabolize the lipid. The main product of the
      metabolism is an intact ring with a short carboxylated side chain which
      glucuronidated in the liver and excreted mainly into the bile (Nakamura et al.,
      Biofactors 9 (1999), 111-119). In other cells CoQ is phosphorylated, transferred
      into the blood and excreted through the urine. The biosynthesis of this lipid is
      regulated by nuclear receptors. PPARalpha is not required for the biosynthesis,
      or induction upon cold exposure, but it is necessary for the elevated CoQ
      synthesis during peroxisomal induction. RXRalpha is involved in the basal
      synthesis of CoQ and also in the increased synthesis upon cold treatment but is
      not required for peroxisomal induction. Dietary CoQ in human appear in the blood
      and it is taken up by mononuclear but not polynuclear cells. The former cells
      display a specific phospholipid modification, an increase of arachidonic acid
      content. In monocytes the CoQ administration leads to a significant decrease of
      the beta2-integrin CD11b and the complement receptor CD35. CD11b is one of the
      adhesion factors regulating the entry of these cells into the arterial wall which
      demonstrates that the anti-atherogenic effect of CoQ is mediated by other
      mechanisms beside its antioxidant protection.

PMID- 14695917
TI  - The biomolecule ubiquinone exerts a variety of biological functions.
AB  - The chemistry of ubiquinone allows reversible addition of single electrons and
      protons. This unique property is used in nature for aerobic energy gain, for
      unilateral proton accumulation, for the generation of reactive oxygen species
      involved in physiological signaling and a variety of pathophysiological events.
      Since several years ubiquinone is also considered to play a major role in the
      control of lipid peroxidation, since this lipophilic biomolecule was recognized
      to recycle alpha-tocopherol radicals back to the chain-breaking form, vitamin E.
      Ubiquinone is therefore a biomolecule which has increasingly focused the interest
      of many research groups due to its alternative pro- and antioxidant activity. We
      have intensively investigated the role of ubiquinone as prooxidant in
      mitochondria and will present experimental evidences on conditions required for
      this function, we will also show that lysosomal ubiquinone has a double function
      as proton translocator and radical source under certain metabolic conditions.
      Furthermore, we have addressed the antioxidant role of ubiquinone and found that
      the efficiency of this activity is widely dependent on the type of biomembrane
      where ubiquinone exerts its chain-breaking activity.

PMID- 14695918
TI  - Specificity of coenzyme Q inhibition of an aging-related cell surface NADH
      oxidase (ECTO-NOX) that generates superoxide.
AB  - Our laboratories have described a novel class of ectoproteins at the cell surface
      with both NADH or hydroquinone oxidase (NOX) and protein disulfide-thiol
      interchange activities (ECTO-NOX proteins). The two activities exhibited by these
      proteins alternate to generate characteristic patterns of oscillations where the
      period length is independent of temperature. The period length for the
      constitutive ECTO-NOX is 24 min. Here we describe a distinctive age-related ECTO
      NOX (arNOX) whose activity is blocked by coenzyme Q10. arNOX occurs exclusively
      in aged cells and tissues. The period length of the oscillations is 26 min.
      Rather than reducing 1/2 O2 to H2O, electrons are transferred to O2 to form
      superoxide. Superoxide formation was demonstrated by superoxide dismutase
      sensitive reduction of ferricytochrome c and by reduction of a superoxide
      specific tetrazolium salt. Quinone inhibition was given by coenzymes Q8, 9 and
      Q10 but not by Q0, Q2, Q4, Q6 or 7. The arNOX provides a mechanism to propagate
      reactive oxygen species generated at the cell surface to surrounding cells and
      circulating lipoproteins of importance to atherogenesis. Inhibition of arNOX by
      dietary coenzyme Q10 provides a rational basis for dietary coenzyme 10 use to
      retard aging-related arterial lesions.

PMID- 14695919
TI  - Regeneration of the antioxidant ubiquinol by lipoamide dehydrogenase, thioredoxin
      reductase and glutathione reductase.
AB  - Ubiquinol is a powerful antioxidant, which is oxidized in action and needs to be
      replaced or regenerated to be capable of a sustained effort. This article
      summarises current knowledge of extramitochondrial reduction of ubiquinone by
      three flavoenzymes, i.e. lipoamide dehydrogenase, glutathione reductase and
      thioredoxin reductase, belonging to the same pyridine nucleotide-disulfide
      oxidoreductase family. These three enzymes are the most efficient
      extramitochondrial ubiquinone reductases so far described. The reduction of
      ubiquinone by lipoamide dehydrogenase and glutathione reductase is potently
      stimulated by zinc and the highest rate of reduction is achieved at acidic pH and
      the rates are equal with either NADPH or NADH as co-factors. The most efficient
      ubiquinone reductases are mammalian cytosolic thioredoxin reductases, which are
      selenoenzymes with a number of biological functions. Reduction of ubiquinone by
      thioredoxin reductase is in contrast to the other two enzymes investigated,
      inhibited by zinc and shows a sharp physiological pH optimum at pH 7.5.
      Furthermore, the reaction is selenium dependent as revealed from experiments
      using truncated and mutant forms of the enzyme and also in a cellular context by
      selenium treatment of transfected thioredoxin reductase overexpressing stable
      cell lines. The reduction of ubiquinone by the three enzymes offers a
      multifunctional system for extramitochondrial regeneration of an important
      antioxidant.

PMID- 14695920
TI  - Effect of UV-C mediated oxidative stress in leukemia cell lines and its relation
      to ubiquinone content.
AB  - UV-C radiation is able to impair cellular functions by directly damaging DNA, and
      by inducing an increased formation of reactive oxygen species that leads to a
      condition of oxidative stress. In this study we evaluated different responses to
      UV insult of two leukemia cell lines, HL-60 and Raji, and the relationship with
      their CoQ10 content. DNA damage was monitored by means of the alkaline single
      cell gel electrophoresis (Comet assay); intracellular levels of ROS,
      mitochondrial depolarization and cell viability was measured by flow cytometry.
      Raji cells appeared more resistant to the UV insult; moreover, they did not show
      any increase in ROS content and the extent of mitochondrial depolarisation was
      much lower than in HL 60 cell line. Raji cells also contained significantly
      higher levels of CoQ10 and their ability to incorporate and to reduce exogenous
      CoQ10 added to the culture medium was remarkably elevated compared with HL 60.

PMID- 14695921
TI  - Coenzyme Q10 reduces the toxicity of rotenone in neuronal cultures by preserving
      the mitochondrial membrane potential.
AB  - Defects in mitochondrial energy metabolism due to respiratory chain disorders
      lead to a decrease in mitochondrial membrane potential (DeltaPsim) and induce
      apoptosis. Since coenzyme Q10 (CoQ10) plays a dual role as an antioxidant and
      bioenergetic agent in the respiratory chain, it has attracted increasing
      attention concerning the prevention of apoptosis in mitochondrial diseases. In
      this study the potential of CoQ10 to antagonize the apoptosis-inducing effects of
      the respiratory chain inhibitor rotenone was explored by video-enhanced
      microscopy in SH-SY5Y neuroblastoma cells. The cationic fluorescent dye JC-1
      which exhibits potential-dependent accumulation in mitochondria was used as an
      indicator to monitor changes in DeltaPsim. The relative changes in fluorescence
      intensity after incubation with rotenone for 15 minutes were calculated. Pre
      treatment with CoQ10 (10 or 100 microM) for 48 h led to a significant reduction
      of rotenone-induced loss of DeltaPsim. These results suggest, that cytoprotection
      by CoQ10 may be mediated by raising cellular resistance against the initiating
      steps of apoptosis, namely the decrease of DeltaPsim. Whether these data may
      provide new directions for the development of neuroprotective strategies has to
      be investigated in future studies.

PMID- 14695922
TI  - Phylloquinone, what can we learn from plants?
AB  - The plant plasma membrane contains redox proteins able to mediate a trans
      membrane electron flow. This electron flow might be responsible for the
      generation of the active oxygen species observed as a reaction to pathogen attack
      or stress. Vitamin K1 could be identified as a possible lipid soluble electron
      carrier in plant plasma membrane preparations. Such a function would be analogous
      to coenzyme Q in animal plasma membranes. What we are going to outline in this
      contribution is a concept of how the electron transport system of the plant
      plasma membrane could interact with quinones, thus contributing to the metabolism
      of free radicals in plants.

PMID- 14695923
TI  - Overview on coenzyme Q10 as adjunctive therapy in chronic heart failure.
      Rationale, design and end-points of "Q-symbio"--a multinational trial.
AB  - Energy starvation of the myocardium is probably a dominant feature of heart
      failure and attention has been directed towards agents which may stabilize
      myocardial metabolism and maintain adequate energy stores. A reduced myocardial
      tissue content of the essential redox-component and natural antioxidant Coenzyme
      Q10 (CoQ10) has been detected in patients with heart failure and the observed
      level of CoQ10 deficiency was correlated to the severity of heart failure. CoQ10
      fulfills various criteria of an obvious adjunct in patients with symptomatic
      heart failure: it is devoid of significant side effects and it improves symptoms
      and quality of life. Till this date, several double-blind placebo-controlled
      trials with CoQ10 supplementation in more than 1000 patients have been positive
      and statistically significant with respect to various clinical parameters, e.g.
      improvement in NYHA Class, exercise capacity and reduced hospitalisation
      frequency. Also treatment with CoQ10 led to a significant improvement of relevant
      hemodynamic parameters. In only 3 out of 13 double-blind studies comprising 10%
      of the total number of patients treated the results were neutral. Thus, based on
      the available controlled data CoQ10 is a promising, effective and safe approach
      in chronic heart failure. This is why a double-blind multicenter trial with focus
      on morbidity and mortality has been planned to start in 2003: Q-SYMBIO. Patients
      in NYHA classes III to IV (N=550) receiving standard therapy are being randomized
      to treatment with CoQ10 100 mg t.i.d. or placebo in parallel groups. End-points
      in a short-term evaluation phase of 3 months include symptoms, functional
      capacity and biomarker status (BNP). The aim of a subsequent 2-year follow-up
      study is to test the hypothesis that CoQ10 may reduce cardiovascular morbidity
      (unplanned cardiovascular hospitalisation due to worsening heart failure) and
      mortality as a composite endpoint. This trial should help to establish the future
      role of CoQ10 as part of a maintenance therapy in patients with chronic heart
      failure.

PMID- 14695924
TI  - Systematic review of effect of coenzyme Q10 in physical exercise, hypertension
      and heart failure.
AB  - COENZYME Q10 IN PHYSICAL EXERCISE. We identified eleven studies in which CoQ10
      was tested for an effect on exercise capacity, six showed a modest improvement in
      exercise capacity with CoQ10 supplementation but five showed no effect. CoQ10 IN
      HYPERTENSION. We identified eight published trials of CoQ10 in hypertension.
      Altogether in the eight studies the mean decrease in systolic blood pressure was
      16 mm Hg and in diastolic blood pressure, 10 mm Hg. Being devoid of significant
      side effects CoQ10 may have a role as an adjunct or alternative to conventional
      agents in the treatment of hypertension. CoQ10 IN HEART FAILURE. We performed a
      randomised double blind placebo-controlled pilot trial of CoQ10 therapy in 35
      patients with heart failure. Over 3 months, in the CoQ10 patients but not in the
      placebo patients there were significant improvements in symptom class and a trend
      towards improvements in exercise time. META-ANALYSIS OF RANDOMISED TRIALS OF
      COENZYME Q10 IN HEART FAILURE. In nine randomised trials of CoQ10 in heart
      failure published up to 2003 there were non-significant trends towards increased
      ejection fraction and reduced mortality. There were insufficient numbers of
      patients for meaningful results. To make more definitive conclusions regarding
      the effect of CoQ10 in cardiac failure we recommend a prospective, randomised
      trial with 200-300 patients per study group. Further trials of CoQ10 in physical
      exercise and in hypertension are recommended.

PMID- 14695925
TI  - The clinical use of HMG CoA-reductase inhibitors and the associated depletion of
      coenzyme Q10. A review of animal and human publications.
AB  - The depletion of the essential nutrient CoQ10 by the increasingly popular
      cholesterol lowering drugs, HMG CoA reductase inhibitors (statins), has grown
      from a level of concern to one of alarm. With ever higher statin potencies and
      dosages, and with a steadily shrinking target LDL cholesterol, the prevalence and
      severity of CoQ10 deficiency is increasing noticeably. An estimated 36 million
      Americans are now candidates for statin drug therapy. Statin-induced CoQ10
      depletion is well documented in animal and human studies with detrimental cardiac
      consequences in both animal models and human trials. This drug-induced nutrient
      deficiency is dose related and more notable in settings of pre-existing CoQ10
      deficiency such as in the elderly and in heart failure. Statin-induced CoQ10
      deficiency is completely preventable with supplemental CoQ10 with no adverse
      impact on the cholesterol lowering or anti-inflammatory properties of the statin
      drugs. We are currently in the midst of a congestive heart failure epidemic in
      the United States, the cause or causes of which are unclear. As physicians, it is
      our duty to be absolutely certain that we are not inadvertently doing harm to our
      patients by creating a wide-spread deficiency of a nutrient critically important
      for normal heart function.

PMID- 14695926
TI  - Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other
      antioxidants and PUFA.
AB  - It has been shown that treating hypercholesterolemic patients (HPC) with statins
      leads to a decrease, at least in plasma, not only in cholesterol, but also in
      important non-sterol compounds such as ubiquinone (CoQ10), and possibly
      dolichols, that derive from the same biosynthetic pathway. Plasma CoQ10 decrease
      might result in impaired antioxidant protection, therefore leading to oxidative
      stress. In the present paper we investigated the levels in plasma, lymphocytes
      and erythrocytes, of ubiquinol and ubiquinone, other enzymatic and non-enzymatic
      lipophilic and hydrophilic antioxidants, polyunsaturated fatty acids of
      phosfolipids and cholesterol ester fractions, as well as unsaturated lipid and
      protein oxidation in 42 hypercholesterolemic patients treated for 3 months. The
      patients were treated with different doses of 3 different statins, i.e.
      atorvastatin 10 mg (n = 10) and 20 mg (n = 7), simvastatin, 10 mg (n = 5) and 20
      mg (n = 10), and pravastatin, 20 mg (n = 5) and 40 mg (n = 5). Simvastatin,
      atorvastatin and pravastatin produced a dose dependent plasma depletion of total
      cholesterol (t-CH), LDL-C, CoQ10H2, and CoQ10, without affecting the
      CoQ10H2/CoQ10 ratio. The other lipophilic antioxidants (d-RRR-alpha-tocopherol
      vit E-, gamma-tocopherol, vit A, lycopene, and beta-carotene), hydrophilic
      antioxidants (vit C and uric acid), as well as, TBA-RS and protein carbonyls were
      also unaffected. Similarly the erythrocyte concentrations of GSH and PUFA, and
      the activities of enzymatic antioxidants (Cu,Zn-SOD, GPx, and CAT) were not
      significantly different from those of the patients before therapy. In lymphocytes
      the reduction concerned CoQ10H2, CoQ10, and vit E; other parameters were not
      investigated. The observed decline of the levels of CoQ10H2 and CoQ10 in plasma
      and of CoQ10H2, CoQ10 and vit E in lymphocytes following a 3 month statin therapy
      might lead to a reduced antioxidant capacity of LDL and lymphocytes, and probably
      of tissues such as liver, that have an elevated HMG-CoA reductase enzymatic
      activity. However, this reduction did not appear to induce a significant
      oxidative stress in blood, since the levels of the other antioxidants, the
      pattern of PUFA as well as the oxidative damage to PUFA and proteins resulted
      unchanged. The concomitant administration of ubiquinone with statins, leading to
      its increase in plasma, lymphocytes and liver may cooperate in counteracting the
      adverse effects of statins, as already pointed out by various authors on the
      basis of human and animal studies.

PMID- 14695927
TI  - Statin cardiomyopathy? A potential role for Co-Enzyme Q10 therapy for statin
      induced changes in diastolic LV performance: description of a clinical protocol.
AB  - Lipid-lowering statins are thought to have a favorable safety profile. Statins
      inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate
      limiting step of mevalonate synthesis. Mevalonate is the substrate for further
      synthesis of cholesterol and Co Enzyme Q10 (CoQ10). CoQ10 plays an important role
      during oxidative phosphorylation in the myocardial cell. Since myocardial
      diastolic function is a highly ATP dependent, we reasoned that early changes of
      diastolic function may be an early marker of ventricular dysfunction. METHODS:
      Patients who are to commence on statin therapy will be enrolled in the trial.
      Baseline measurements of plasma CoQ10, total cholesterol, LDL, HDL, CoQ10/LDL
      ratio, peak E, peak A velocities, E/A ratio, deceleration time, isovolumetric
      relaxation time, color M-mode propagation velocity will be performed and patients
      will then begin to take Oral atorvastatin (Lipitor, Parke-Davis) 20 mg daily for
      three to six months. All baseline measurement will be repeated after 3 to 6
      months of statin therapy. Those patients demonstrating > 1 measurement of
      diastolic LV function that worsened during the 3 to 6 months of statin therapy
      will be supplemented with CoQ10 300 mg. daily for 3 months. A followup
      echocardiogram and blood CoQ10 level will be measured in patients who received
      CoQ10 supplementation. RESULTS: Statistical analysis will be performed using the
      paired t test to compare coenzyme levels and echocardiographic indices at
      baseline and after treatment and after supplementation.

PMID- 14695928
TI  - Can coenzyme Q10 improve vascular function and blood pressure? Potential for
      effective therapeutic reduction in vascular oxidative stress.
AB  - Coenzyme Q10 (CoQ) is an endogenously synthesised compound that acts as an
      electron carrier in the mitochondrial electron transport chain. The presence of
      adequate tissue concentrations of CoQ may be important in limiting oxidative and
      nitrosative damage in vivo. Oxidative and nitrosative stress are likely to be
      elevated in conditions such as diabetes and hypertension. In these conditions
      elevated oxidative and nitrosative stress within the arterial wall may contribute
      to increased blood pressure and vascular dysfunction. The major focus of this
      review is the potential of CoQ to improve vascular function and lower blood
      pressure. Although there is substantial indirect support for the putative
      mechanism of effect of CoQ on the vascular system, to date there is little direct
      support for an effect of CoQ on in vivo markers of oxidative or nitrosative
      stress. The limited data available from studies in animal models and from human
      intervention studies are generally consistent with a benefit of CoQ on vascular
      function and blood pressure. The observed effects of CoQ on these endpoints are
      potentially important therapeutically. However, before any firm clinical
      recommendations can be made about CoQ supplementation, further intervention
      studies in humans are needed to investigate the effects of CoQ on vascular
      function, blood pressure and cardiovascular outcomes. The particularly relevant
      groups of patients for these studies are those with insulin resistance, type 2
      diabetes, hypertension and the metabolic syndrome.

PMID- 14695929
TI  - Relaxation of arterial smooth muscle: a new function of a water-soluble
      degradation product of coenzyme Q (ubiquinone).
AB  - Treatment of coenzyme Q with ozone yielded a degradation product having
      unmodified ring that retained its spectral characteristics and a truncated side
      chain that made it water-soluble. This derivative, but not the intact lipid
      quinone, showed relaxation of phenylephrine-contracted rat arterial rings. This
      effect offers an explanation for the known hypotensive action of exogenous
      coenzyme Q regardless of its side-chain length.

PMID- 14695930
TI  - Primary coenzyme Q10 deficiency and the brain.
AB  - Our findings in 19 new patients with cerebellar ataxia establish the existence of
      an ataxic syndrome due to primary CoQ10 deficiency and responsive to CoQ10
      therapy. As all patients presented cerebellar ataxia and cerebellar atrophy, this
      suggests a selective vulnerability of the cerebellum to CoQ10 deficiency. We
      investigated the regional distribution of coenzyme Q10 in the brain of adult rats
      and in the brain of one human subject. We also evaluated the levels of coenzyme
      Q9 (CoQ9) and CoQ10 in different brain regions and in visceral tissues of rats
      before and after oral administration of CoQ10. Our results show that in rats,
      amongst the seven brain regions studied, cerebellum contains the lowest level of
      CoQ. However, the relative proportion of CoQ10 was the same (about 30% of total
      CoQ) in all regions studied. The level of CoQ10 is much higher in brain than in
      blood or visceral tissue, such as liver, heart, or kidney. Daily oral
      administration of CoQ10 led to substantial increases of CoQ10 concentrations only
      in blood and liver. Of the four regions of one human brain studied, cerebellum
      again had the lowest CoQ10y concentration.

PMID- 14695931
TI  - Effects of Coenzyme Q10 in Huntington's disease and early Parkinson's disease.

PMID- 14695932
TI  - Friedreich's Ataxia: disease mechanisms, antioxidant and Coenzyme Q10 therapy.
AB  - Mitochondria clearly play a central role in the pathogenesis of Friedreich's
      Ataxia. The most common genetic abnormality results in the deficiency of the
      protein frataxin, which is targeted to the mitochondrion. Research since this
      discovery has indicated that mitochondrial respiratory chain dysfunction,
      mitochondrial iron accumulation and oxidative damage are important components of
      the disease mechanism. While the role of frataxin is not known, evidence is
      currently pointing to a role in either mitochondrial iron handling or iron
      sulphur centre synthesis. These advances in our understanding of the disease
      mechanisms are enabling therapeutic avenues to be explored, in particular the use
      of established drugs such as antioxidants and enhancers of respiratory chain
      function. Vitamin E therapy has been shown to be beneficial in patients with
      ataxia with vitamin E deficiency, and CoQ10 therapy was effective in some
      patients with ataxia associated with CoQ10 deficiency. A combined therapy
      involving long term treatment with high doses of vitamin E and coenzyme Q10 has
      jointly targeted two of the major features of Friedreich's Ataxia; decreased
      mitochondrial respiratory chain function and increased oxidative stress. This
      therapy clearly showed a rapid and sustained increase in the energy generated by
      the FRDA heart muscle, nearly returning to normal levels. The improvements in
      skeletal muscle energy generation parallel those of the heart but to a lower
      level. While this therapy appeared to slow the predicted progression of some
      clinical symptoms a larger placebo controlled study is required to confirm these
      observations. Other antioxidant strategies have involved the use of Idebenone,
      selenium and N acetyl cysteine but only the use of Idebenone has involved
      structured trials with relatively large patient numbers. Idebenone clearly had an
      impact upon the cardiac hypertrophy in the majority of patients, although there
      have not been any other significant benefits reported to date.

PMID- 14695933
TI  - Derivatised alpha-tocopherol as a CoQ10 carrier in a novel water-soluble
      formulation.
AB  - We have derivatised alpha-tocopherol (vitamin E) to a water-soluble
      polyoxyethanyl-alpha - tocopheryl sebacate (PTS) and discovered that it formed a
      non-covalent complex with CoQ10 at a molar ratio of 2:1 (PTS-CoQ10). This complex
      was water-soluble and remained stable for extended periods of time. After oral
      delivery of the formulation into rats PTS was hydrolysed to vitamin E and
      elevated levels of both vitamin E and CoQ10 in blood plasma were detected within
      1 h. Thus, this aqueous formulation contains a combination of two potent
      antioxidants. The formulation's efficacy was tested against ischemic brain damage
      caused by a transient (8 min) bilateral occlusion of the common carotid arteries
      in rats. The animals received PTS-CoQ10 by two intraperitoneal injections given
      immediately after ischemia and 3 h later and the brain damage was assessed up to
      12 days post-ischemia. A significant neuroprotection was observed in the CA1
      hippocampal region, for example at 12 days approximately 50% of CA1 neurons were
      still alive in the treated animals versus less than 5% in the non-treated group.
      Our data is consistent with previously published observations indicating the
      therapeutic potential of antioxidants for treatments of ischemia/reperfusion
      injuries and the formulation described here is particularly appropriate for the
      application in acute conditions, such as stroke or cardiac arrest.

PMID- 14695934
TI  - Serum coenzyme Q10 concentrations in healthy men supplemented with 30 mg or 100
      mg coenzyme Q10 for two months in a randomised controlled study.
AB  - Serum coenzyme Q10 (Q10) concentrations were evaluated in healthy male volunteers
      supplemented with 30 mg or 100 mg Q10 or placebo as a single daily dose for two
      months in a randomised, double-blind, placebo-controlled study. Median baseline
      serum Q10 concentration in 99 men was 1.26 mg/l (10%, 90% fractiles: 0.82, 1.83).
      Baseline serum Q10 concentration did not depend on age, while borderline
      significant positive associations were found for body weight and smoking 1-10
      cigarettes/d. Supplementation with 30 mg or 100 mg Q10 resulted in median
      increases in serum Q10 concentration of 0.55 mg/l and 1.36 mg/l, respectively,
      compared with a median decrease of 0.23 mg/l with placebo. The changes in the Q10
      groups were significantly different from that in the placebo group, and the
      increase in the 100 mg Q10 group was significantly greater than that in the 30 mg
      Q10 group. The change in serum Q10 concentration in the Q10 groups did not depend
      on baseline serum Q10 concentration, age, or body weight.

PMID- 14695935
TI  - Cytoprotective and anticancer properties of coenzyme Q versus capsaicin.
AB  - Coenzyme Q (CoQ) is an essential component of the mitochondrial electron
      transport chain and serves as an electron donor and acceptor in mitochondrial
      energy-linked respiration. CoQ1 was shown to prevent ROS formation and cell death
      in complex 1 inhibited cells. Low concentrations of capsaicin like CoQ1 inhibited
      ROS formation but CoQ1 was more effective at restoring the mitochondrial membrane
      potential collapse caused by complex 1 inhibitors such as rotenone. At low
      concentrations, capsaicin acts as a CoQ mimic by protecting against rotenone
      induced ROS formation and mitochondrial membrane potential collapse. Lipid
      peroxidation in isolated rat hepatocytes induced by cumene hydroperoxide and
      chloroacetaldehyde was also prevented. At higher concentrations, capsaicin and
      CoQ1 became cytotoxic. Hep G2 cells were more susceptible than hepatocytes. The
      cytotoxic mechanism for both capsaicin and CoQ1 was shown to involve a collapse
      of the mitochondrial membrane potential, however, only capsaicin caused ROS
      formation. The capsaicin side chain was required for capsaicin induced
      cytotoxicity. The anticancer properties of CoQ1 and capsaicin should prove useful
      for inducing tumor cell apoptosis.

PMID- 14695936
TI  - Hepatocyte metabolism of coenzyme Q1 (ubiquinone-5) to its sulfate conjugate
      decreases its antioxidant activity.
AB  - Previous studies on the metabolism of coenyzme Q (CoQ) have focused on products
      found in the urine, bile or feces. However, the metabolites found in these
      samples were end products from a multitude of catabolic processes which did not
      necessarily reflect CoQ intracellular metabolism (e.g. in the liver, the major
      site of CoQ synthesis or metabolism). Using isolated rat hepatocytes, we have
      found that the sulfation of coenzyme Q1 (CoQ1) was the initial and dominant step
      following its reduction to the hydroquinone. This metabolic process is important
      as conjugation may occur on the hydroquinone metabolites of any coenzyme10
      scission product retaining the quinone ring. By using rat liver cytosol, we were
      able to identify the monosulfated metabolite of CoQ1. The CoQ1 sulfate conjugate
      was identified by mass spectrometry followed by tandem mass spectrometry. The
      rate of formation of the CoQ1 sulfate conjugate was markedly increased by the
      addition of NADH and was prevented by dicumarol, a DT-diaphorase (NQO1)
      inhibitor. CoQ1 sulfate conjugate formation catalysed by cytosol was inhibited by
      the sulfotransferase 1A (SULT1A) inhibitor, pentachlorophenol (PCP) suggesting
      that sulfation was carried out by the SULT 1A isoform. CoQ1 sulfation in isolated
      hepatocytes and inversely CoQ1 hydroquinone formation were dependent on the
      concentration of inorganic sulfate in the media. Intracellular sulfation also
      decreased CoQ1 antioxidant and cytoprotective activity towards cumene
      hydroperoxide (CHP) induced cell death. Sulfotransferases may therefore play a
      significant role in endogenous CoQ metabolism following its degradation to short
      chain products.

PMID- 14695937
TI  - Antioxidant response induced by serum withdrawal protects HL-60 cells against
      inhibition of NAD(P)H:quinone oxidoreductase 1.
AB  - We have previously shown that inhibition of NAD(P)H:quinone acceptor
      oxidoreductase 1 with dicoumarol decreases growth and viability of HL-60 cells in
      the absence of serum. Here we demonstrate that culturing HL-60 cells in serum
      free medium in the presence of dicoumarol results in a significant potentiation
      of apoptosis. However, when cells were preincubated for 24 h without serum before
      they were treated with dicoumarol, the effect of the inhibitor on cell growth and
      death was much lower. We have investigated cellular changes induced in HL-60
      cells by removal of serum that could account for protection against the effects
      of dicoumarol. Serum removal induced significant increases of NAD(P)H:quinone
      acceptor oxidoreductase 1, particularly at 32 h after serum withdrawal. Total
      amounts of ubiquinone in cells were unchanged but, its reduction state paralleled
      the observed increase in quinone reductase activity. Levels of the antiapoptotic
      protein Bcl-2 were also significantly increased after serum removal. Our results
      indicate that removal of serum evokes an antioxidant protective response that
      make HL-60 cells less sensitive to cell death induced by inhibition of
      NAD(P)H:quinone acceptor oxidoreductase 1 with dicoumarol.

PMID- 14695938
TI  - Pleiotropic phenotypes of fission yeast defective in ubiquinone-10 production. A
      study from the abc1Sp (coq8Sp) mutant.
AB  - We previously constructed two Schizosaccahromyces pombe ubiquinone-10 (or
      Coenzyme Q10) less mutants, which are either defective for decaprenyl diphosphate
      synthase or p-hydroxybenzoate polyprenyl diphosphate transferase. To further
      confirm the roles of ubiquinone in S. pombe, we examined the phenotype of the
      abc1Sp (coq8Sp) mutant, which is highly speculated to be defective in ubiquinone
      biosynthesis. We show here that the abc1Sp defective strain did not produce UQ-10
      and could not grow on minimal medium. The abc1Sp-deficient strain required
      supplementation with antioxidants such as cysteine or glutathione to grow on
      minimal medium. In support of the antioxidant function of ubiquinone, the abc1Sp
      deficient strain is sensitive to H2O2 and Cu2+. In addition, expression of the
      stress inducible ctt1 gene was much induced in the ubiquinone less mutant than
      wild type. Interestingly, we also found that the abc1-deficient strain as well as
      other ubiquinone less mutants produced a significant amount of H2S, which
      suggests that oxidation of sulfide by ubiquinone may be an important pathway for
      sulfur metabolism in S. pombe. Thus, analysis of the phenotypes of S. pombe
      ubiquinone less mutants clearly demonstrate that ubiquinone has multiple
      functions in the cell apart from being an integral component of the electron
      transfer system.

PMID- 14695939
TI  - Caenorhabditis elegans ubiquinone biosynthesis genes.
AB  - Ubiquinone (coenzyme Q, Q) is an essential lipid electron carrier in the
      mitochondria respiratory chain, and also functions as antioxidant and
      participates as a cofactor of mitochondrial uncoupling proteins. Caernorhabditis
      elegans synthesize Q9, but both dietary Q8 intake and endogenous Q9 biosynthesis
      determine Q balance. Thus, it is of current interest to know the regulatory
      mechanisms of Q9 biosynthesis in this nematode. Here we review results that
      leaded to identification of genes involved in Q9 biosynthesis in this nematode
      using the RNA interference technology. C. elegans coq genes were silenced and
      depletion of Q content was observed, indicating that the genes related here
      participate in Q9 biosynthesis. Silenced populations showed an extension of adult
      life span, probably by the decrease of endogenous oxidative stress produced in
      mitochondria. We also report the heterologous complementation of C. elegans coq-5
      and coq-7 genes in their homologue yeast coq null mutants, leading to restore its
      ability to growth in non-fermentable sugars. These complemented yeast strains
      accumulated Q6 but also the intermediate demethoxy-Q6. These findings support the
      conservative functional homology of these genes.

PMID- 14695940
TI  - Coenzyme Q10-containing composition (Immugen) protects against occupational and
      environmental stress in workers of the gas and oil industry.
AB  - The manual workers of the gas-and-oil extraction industry are exposed to hostile
      environmental and occupational conditions, resulting in elevated mortality and
      disability, due to chronic neurological and cardiovascular diseases. We evaluated
      the degree of oxidative stress, often associated with these pathological
      features, in the blood of manual and office employees of Russian Siberian
      extraction plants, and their psycho-physiological conditions. Results showed
      increased levels of spontaneous (p < 0.05) and PMA-activated (p < 0.01) luminol
      dependent chemiluminescence (LDCL) in the white blood cells (WBC), and decreased
      peroxynitrite levels (p < 0.05) in the group of manual workers, and less markedly
      in the clerks and technicians working on spot, vs. a control group of city
      clerks. Superoxide release by WBC, and plasma/WBC membrane ubiquinol levels did
      not display major differences in the three groups. A relevant percentage of
      manual/office workers of extraction platforms presented impaired cardiovascular
      and neurological functions. The short term administration of a nutraceutical
      formulation based on coenzyme10, vitamin E, selenium, methionine and
      phospholipids led to significant improvement of cardiovascular parameters and
      psycho-emotional status, consistent with the normalization of LDCL and
      peroxynitrite production by WBC, with a good compliance to treatment confirmed by
      the increased blood levels of ubiquinol.

PMID- 14695941
TI  - The protective and healing effects of a natural antioxidant formulation based on
      ubiquinol and Aloe vera against dextran sulfate-induced ulcerative colitis in
      rats.
AB  - Oxygen/nitrogen reactive species (ROS/RNS) are currently implicated in the
      pathogenesis of ulcerative colitis, drawing attention on the potential
      prophylactic and healing properties of antioxidants, scavengers, chelators. We
      evaluated the possible protective/curative effects of a natural antioxidant
      preparation based on Aloe vera and ubiquinol, against intestinal inflammation,
      lesions, and pathological alterations of the intestinal electrophysiological
      activity and motility, in a rat model of DSS-induced colitis. 5% dextrane sulfate
      (DDS) (3 days), followed by 1% DSS (4 days) was administered in drinking water.
      The antioxidant formulation (25 mg/kg) was delivered with a pre-treatment
      protocol, or simultaneously or post-colitis induction. Spontaneous and
      acetylcholine-stimulated electrical activity were impaired in the small intestine
      and in distal colon, upon exposure to DSS only. Severe inflammation occurred,
      with increased myeloperoxidase activity, and significant alterations of the
      oxidant/antioxidant status in colonic tissue and peritoneal cells.
      Lipoperoxidation, superoxide production, glutathione peroxidase and glutathione-S
      transferase activities, and reduced glutathione content increased, whilst
      superoxide dismutase and catalase activities were sharply suppressed in colon
      tissue. ROS/RNS formation in peritoneal cells was strongly inhibited.
      Inflammation, electrical/mechanical impairment in the gut, and a great majority
      of oxidative stress parameters were improved substantially by pre-treatment with
      the antioxidant preparation, but not by simultaneous administration or post
      treatment.

PMID- 14695942
TI  - Coenzyme Q differentially modulates phospholipid hydroperoxide glutathione
      peroxidase gene expression and free radicals production in malignant and non
      malignant prostate cells.
AB  - The aim of this study was to investigate the role of coenzyme Q on the mRNA
      abundance of PHGPx and the reactive oxygen species (ROS) production in two
      different cell lines from human prostate, a line of non cancer cells (PNT2) and a
      line of cancer cells (PC3). Results showed that malignant cells markedly differ
      in their response to coenzyme Q compared to non-malignant cells, with no changes
      in PHGPx expression and greater ROS production. Furthermore coenzyme Q
      supplementation significantly lowered cell growth of the PC3 cancer line without
      affecting the PNT2. If these results are confirmed with additional experiments,
      it could represent a novel and interesting approach on the biomedical use of
      coenzyme Q10 in cancer therapy.

PMID- 14695943
TI  - The effect of Cyclosporine A chronic administration on the antioxidant pattern of
      rat liver mitochondria: structural and functional consequences.
AB  - Cyclosporine A (CsA) plays a pivotal role in controlling Ca2+ movement in the
      cell modulating also the mitochondrial permeability transition pore. We
      investigated if chronic administration of CsA may have some effects on the
      lipophilic and hydrophilic antioxidant pattern of rat liver mitochondria and on
      their morphological structure. It seems that CsA administration does not
      statistically affect the redox status of the antioxidants investigated and their
      amounts (vitamin E, CoQ9, CoQ10, glutathione, uric acid and ascorbic acid)
      despite the variety of effects that this treatment produces at physiological and
      morphological levels. However, some kind of derangement could occur in the liver
      biochemical machinery since CsA treatment induces a markedly increased
      variability in antioxidant contents.

PMID- 14695944
TI  - Coenzyme Q, Vitamin E and Apo-E alleles in Alzheimer Disease.
AB  - Neurodegenerative Diseases represent the most common cause of Dementia, about 5
      10% of the population aged above 65 years and about 30% above 80 years. A study
      about Apo-E alleles, Coenzyme Q and Vitamins E as biological indicators was
      performed in plasma samples of patients aged from 30 to 85 years, affected by
      Neurodegenerative Diseases. The results were compared with control subjects of
      approximately the same ages as the reference group. A frequency of 21.7% of
      epsilon4 allele in control group was estimated, against 15.8% observed in
      patients. The frequency of epsilon2 and epsilon3 alleles was 13.0% and 65.2% in
      the control group against 10.5% and 73.7% in patients. No significant differences
      were observed between the frequency of epsilon3/epsilon3 genotype and
      epsilon3/epsilon4 genotype in the control group compared to patients' group. The
      frequencies observed in epsilon2/epsilon3 genotype groups were 8.7% vs 15.8% and
      of e2/e4 genotype 17.4% vs 5.3%. The epsilon2/epsilon2 and epsilon4/epsilon4
      genotypes were not identified in any groups. Plasma CoQ10 concentrations were
      similar in patient and control groups and no differences were found even taking
      into account the distribution of male and female subjects in the two groups.
      Also, vitamin E did not provide evidence of any differences between groups and
      the analysis among sexes revealed that again vitamin E concentrations were
      similar in between subgroups.

PMID- 14695945
TI  - The effects of Coenzyme Q10 on locomotor and behavioral activity in young and
      aged C57BL/6 mice.
AB  - To explore the possibility that Coenzyme Q10 (CoQ10) supplementation stabilizes
      psychomotor behavioral function in the aging organism, the behavioral effects of
      CoQ10 were evaluated in young adult male C57BL/6 mice (3 months of age) and aged
      C57BL/6 mice (24 months of age). Mice treated with CoQ10 exhibited significantly
      greater locomotor activity as reflected by an increase in square crosses than non
      drug controls. The administration of CoQ10 increased all aspects of exploratory
      behavior in the open field. The effect was uniform across all mice and did not
      interact with age. Younger animals and aged animals treated with CoQ10 may adapt
      rapidly to novel areas, or they are less fearful of exploration. The behavioral
      activation observed in CoQ10 treated mice may be the result of increased
      locomotor activity, psychomotor stimulation, or decreased anxiety.

PMID- 14695946
TI  - The combined use of oral and topical lipophilic antioxidants increases their
      levels both in sebum and stratum corneum.
AB  - The concentration of Vitamin E (vit E) and ubiquinone (CoQ10), which together
      with squalene (SQ), play a key role against external oxidative insult, has been
      shown to decrease significantly during ageing. The aim of the present study is to
      inquire the effect of the combined use of topical bio-cosmetics containing
      natural active principles (including sebum-like lipid fractions, sebum and
      epidermal lipophilic and hydrophilic antioxidants), and oral antioxidant
      supplements on the antioxidant content of sebum and stratum corneum. We therefore
      treated the face and the back of 50 female volunteers aged 21-40, daily for two
      months, with a base cream containing 0.05% ubiquinone, 0.1% vit E, and 1%
      squalene. In addition 50 mg of CoQ10 + 50 mg of d-RRR-alpha-tocopheryl acetate +
      50 microg of selenium were administered orally to half of the volunteers (Group
      A). Group B was represented by 25 volunteers who were treated only topically.
      Every 15 days during treatment the levels of CoQ10, vit E and SQ were verified in
      sebum, stratum corneum, and plasma. The daily topical application of the cream
      led to a significant increase, that peaked after 60 days, of the levels of CoQ10,
      d-RRR-alpha-tocopherol and SQ in the sebum (Group B), without significantly
      affecting the stratum corneum or plasma concentrations of the redox couple
      CoQ10H2/CoQ10 and vit E. The concomitant oral admistration of antioxidants
      produced in Group A a significant increase of the levels of CoQ10H2/CoQ10 and vit
      E both in plasma and stratum corneum after 15 and 30 days treatment respectively,
      compared to Group B. However the sebum levels of lipophilic antioxidants and SQ
      did not show a significant increase. After the treatments, the levels of
      CoQ10H2/CoQ10, vit E and SQ went back to basal levels within 6-8 days in sebum,
      12-16 days in the stratum corneum, and 3-6 days in plasma. Therefore topical
      application of the antioxidants was able to increase their level in sebum, while
      the concomitant oral administration also affected the levels of vit E and CoQ10
      in the stratum corneum.

PMID- 14695947
TI  - Coenzyme Q10, antioxidant status and ApoE isoforms.
AB  - The aim of this study was to inquire the antioxidant status in plasma and
      lipoproteins isolated from normal subjects possessing different ApoE genotypes.
      For this purpose we investigated blood samples from 106 healthy blood donors: the
      distribution of ApoE alleles (E2/E2 = 0.9%, E2/E3 = 10.4%, E2/E4 = 2.8%, E3/E3 =
      71.7%, E3/E4 = 12.3% and E4/E4 1.9% with 1, 11, 3, 76, 13, and 2 subjects
      respectively for each genotype) was in agreement with previous data. Almost no
      differences were found in the concentrations of both coenzyme Q10 (CoQ10) and
      vitamin E for the different genotypes. Concentration of CoQ10 in isolated
      lipoproteins was also similar, in the different genotypes, when referred to
      cholesterol; CoQ10 in LDL was higher for the E3/E3 subjects when referred to
      protein. Neither CoQ10 nor vitamin E correlated with paraoxonase (PON) activity
      or cholesteryl-ester hydroperoxides (CHP). Furthermore, there was no correlation
      between the same lipophilic antioxidants and CHP levels. The only E2 homozygous
      subject found had high levels of PON and low levels of CHP; the two E4/E4
      subjects had low PON activity together with low levels of CHP.

PMID- 14695948
TI  - Effect of analogs with modified prenyl side chains on growth of serum deficient
      HL60 cells.
AB  - This study was organized by Professor Karl Folkers with the objective of finding
      derivatives of coenzyme Q which could be more effectively absorbed and would give
      better biomedical effects. In this series all the compounds are 2,3 dimethoxy, 5
      methyl p benzoquinone with modified side chains in the 6 position. The
      modifications are primarily changes in chain length, unsaturation, methyl groups
      and addition of terminal phenyl groups. The test system evaluates the growth of
      serum deficient HL60, 3T3 and HeLa cells in the presence of coenzyme Q10 or
      coenzyme Q analogs. Short chain coenzyme Q homologues such as coenzyme Q2 give
      poor growth but compounds with saturated short aliphatic side chains from C10 to
      C18 produce good growth. Introduction of a single double bond at the 2' or 8'
      position in the aliphatic chain retains growth stimulation at low concentration
      but introduces inhibition at higher concentration. Introduction of a 3' methyl
      group in addition to the 2' enyl site in the side chain decreases the growth
      response and maintains inhibition. Addition of a terminal phenyl group to the
      side chain from C5 to C10 can produce analogs which give strong stimulation or
      strong inhibition of growth. The action of the analogs is in addition to the
      natural coenzyme Q in the cell and is not based on restoration of activity after
      depletion of normal coenzyme Q. The effects may be based on any of the sites in
      the cell where coenzyme Q functions. For example, coenzyme Q2 is known to
      decrease mitochondrial membrane potential whereas the analog with a 10C aliphatic
      side chain increases potential. Both of these compounds stimulate plasma membrane
      electron transport. Inhibition of apoptosis by coenzyme Q may also increase net
      cell proliferation and the 10C analog inhibits the permeability transition pore.

PMID- 14695949
TI  - From the ASTDA.

PMID- 14695950
TI  - A Funny Thing Happened on the Way to FHI.

PMID- 14695951
TI  - The prevalence of psychiatric disorders in sexually transmitted disease clinic
      patients and their association with sexually transmitted disease risk.
AB  - BACKGROUND AND OBJECTIVES: Psychiatric disorders could limit the success of
      behavioral counseling strategies. We evaluated the prevalence of psychiatric
      disorders among sexually transmitted disease (STD) clinic patients and their
      association with STD risk. METHODS: A systematic sample of 201 patients
      presenting to a public STD clinic in Baltimore, Maryland, participated in the
      structured clinical interview for the Diagnostic and Statistical Manual of Mental
      Disorders, 4th edition. RESULTS: Overall, 45% of 201 STD clinic patients
      interviewed had a current axis I disorder and 29% had an axis II personality
      disorder. Substance use disorders predominated among axis I diagnoses; antisocial
      personality disorder (ASPD) predominated among axis II diagnoses, with an ASPD
      prevalence of 29.4% in men. ASPD was associated with a diagnosis of an STD (odds
      ratio, 3.67; 95% confidence interval, 1.63-8.30; P = 0.002). Substance use was
      not associated with an STD diagnosis. CONCLUSIONS: STD clinic patients have
      complex psychopathology that could increase HIV risk and compromise prevention
      interventions. Specialized counseling strategies, particularly targeting
      personality traits of ASPD, could improve prevention outcomes.

PMID- 14695952
TI  - Mental health: a powerful predictor of sexual health?

PMID- 14695953
TI  - Intravenous drug use among street-based sex workers: a high-risk behavior for HIV
      transmission.
AB  - BACKGROUND: HIV prevalence among sex workers in Ho Chi Minh City has increased
      rapidly, from 6.5% in 1999 to 18.1% in 2000. This study examined whether
      injecting drug use among street-based sex workers (SSWs) in Ho Chi Minh City is a
      high-risk factor for HIV infection. GOAL: The goal of this study was to determine
      the correlates and prevalence of intravenous drug users among SSWs in Ho Chi Minh
      City. STUDY DESIGN: A cross-sectional study was conducted among SSWs in Ho Chi
      Minh City during December 2000. The SSWs were interviewed and tested for HIV-1.
      RESULTS: HIV-1 seroprevalence was 16.3%. Regression analysis indicated that
      injecting drugs and being younger than 25 years of age were independently
      associated with HIV seropositivity. CONCLUSION: Young SSWs who inject drugs are
      at the greatest risk of contracting HIV and acting as a bridge for HIV to the
      sexually active population.

PMID- 14695954
TI  - Syphilis outbreak among Hispanic immigrants in Decatur, Alabama: association with
      commercial sex.
AB  - BACKGROUND: Despite national progress in syphilis control, increases in rates
      have recently occurred, and syphilis is still an endemic problem in the southern
      United States. An outbreak of infectious syphilis among Hispanics was identified
      in Decatur, Alabama. GOAL: An investigation was initiated to describe the
      outbreak and to assist with prevention activities. STUDY DESIGN: We reviewed case
      interview records and syphilis surveillance data. The Morgan County Health
      Department (MCHD) performed voluntary door-to-door syphilis screening in
      neighborhoods where a large number of cases had been identified. During screening
      activities, sociodemographic and behavioral data were collected. RESULTS: From
      June 2000 to February 2001, 49 cases of syphilis were reported; 26 (53%) were
      primary or secondary, 17 (35%) were early latent, and 6 (12%) late latent. Of the
      early syphilis cases, 70% were male and half were Hispanic; 93% of cases were
      linked to commercial sex and 70% of female cases reported crack cocaine use.
      During the screening, 172 individuals completed a questionnaire; 70% of
      participants were male, 83% were Hispanic, 17% of Hispanic participants spoke
      English, 21% reported sex with a commercial sex worker, and 8 (5%) had positive
      syphilis serology. Among men, factors associated with commercial sex were not
      having a regular partner (odds ratio [OR], 3.9; confidence interval [CI], 1.1
      14.3), not living with a family member in the United States (OR, 4.5; CI, 1.6
      12.8), and having visited their country of origin since arrival to the United
      States (OR, 9.2; CI, 2.3-36.5). CONCLUSIONS: Factors contributing to this
      outbreak were crack cocaine use and increased prostitution in close proximity to
      the Hispanic community. At present, there are an increasing number of Hispanic
      immigrants in the United States, the majority of whom do not speak English. To
      prevent similar outbreaks in the future, public health officials need to be aware
      of the health and health education needs of these populations.

PMID- 14695955
TI  - Effectiveness of self-referral for male patients with urethral discharge
      attending a sexually transmitted disease clinic in China.
AB  - BACKGROUND: Although partner notification (PN) has long been considered as an
      important component in sexually transmitted disease (STD) control programs and
      has been implemented in both developed and developing world, little information
      is known about the acceptability and efficacy of the strategy in China. GOAL: The
      goal of this study was to assess the acceptability and outcome of self-referral
      for male patients with urethral discharge and to identify the characteristics
      associated with successful outcome based on a specialized STD clinic. METHODS:
      From November 2001 to November 2002, 730 patients with confirmed urethral
      discharge were selected and asked by STD clinicians to bring their sexual
      contacts to treatment in a specialized STD clinic. The demographic and sexual
      characteristics of returned and unreturned index patients were analyzed.
      Univariate and multivariate analyses were applied to identify the characteristics
      associated with the outcome of self-referral. RESULTS: Of 723 eligible index
      patients, 294 (40.7%) who returned for follow up identified 534 sexual partners
      and 429 (59.3%) who did not return for follow up identified 759 sexual partners.
      Of the total named 1293 sexual partners, 301 (23.3%) were notified by index male
      patients and 265 (20.5%) presented at the clinic. Of the 265 partners tested, 165
      (62.3%) were infected with gonorrhea, chlamydia, or both; of them, 78 (47.3%)
      were asymptomatic. When the partnerships were married and steady, the informed
      rate was higher than that when the partnership was casual. For commercial sexual
      partnerships, only 1.8% of the partners were informed. In multivariate analysis,
      a prior STD history and condom use during the last sexual contact were associated
      with successful outcome of notification. CONCLUSION: Patient referral was
      accepted both by STD clinic attendees and STD clinicians. The results of the
      study show that use of self-referral for partners of men with urethral discharge
      in a Chinese STD clinic was, with minimal effort, moderately successful. Further
      efforts to improve case-finding outcomes are warranted.

PMID- 14695956
TI  - Congenital syphilis: identification of two distinct profiles of maternal
      characteristics associated with risk.
AB  - BACKGROUND: Behavioral and socioeconomic factors create considerable obstacles to
      the elimination of congenital syphilis. A clear understanding of maternal risk
      factors is important to define interventions in every community. GOAL: The goal
      of this study was to investigate maternal risk factors for congenital syphilis.
      STUDY DESIGN: We conducted a case-control and descriptive analysis of 3 groups of
      live born infants and their mothers consisting of: group I (cases of congenital
      syphilis), group II (neonates without congenital syphilis whose mothers had been
      adequately treated for syphilis), and group III (random sample of newborn infants
      whose mothers have not had syphilis). Data were prospectively collected from
      personal interview and antenatal records. RESULTS: In the case-control study,
      including groups I and III, the maternal characteristics independently associated
      with congenital syphilis in the logistic regression were monthly per capita
      income under 30 US dollars (odds ratio [OR], 2.8; 95% confidence interval [CI],
      1.1-7.4), single status (OR, 2.8; 95% CI, 1.1-7.8), and less than 6 prenatal
      visits (OR, 3.2; 95% CI, 1.3-8.1). Comparison between groups I and II (only
      mothers who have had syphilis) showed a strong protective association of prenatal
      care with congenital syphilis (OR, 0.05; 95% CI, 0.00-0.39). Additional analysis
      identified 2 separate profiles of maternal characteristics, one consisting of low
      socioeconomic status and the other of risk behaviors. Some women who had syphilis
      before or during pregnancy received adequate prenatal care and delivered infants
      without congenital syphilis. Most of these women had high-risk behaviors but they
      were, in general, less poor, older, and more educated than mothers of infants
      with congenital syphilis. CONCLUSIONS: Risk behaviors and low socioeconomic
      characteristics constituted 2 separate maternal profiles associated with
      congenital syphilis. Socioeconomic risk factors interfered more with prenatal
      care. To become more effective, the strategies for prevention of congenital
      syphilis should be targeted to each maternal profile.

PMID- 14695957
TI  - Testing for chlamydial and gonorrheal infections outside of clinic settings: a
      summary of the literature.
AB  - BACKGROUND: Nucleic acid amplification tests (NAATs) provide new technology that
      makes it feasible to initiate testing for Chlamydia trachomatis (CT) and
      Neisseria gonorrhoeae (GC) infection outside of clinic settings. METHODS: We
      summarized the English-language literature describing chlamydial or gonorrheal
      testing with self-collection of urine or vaginal specimens outside of clinic
      settings in developed countries published between January 1995 and August 2002.
      RESULTS: Testing for CT or GC infection has been initiated in school, community,
      and home settings. Purposes include screening of asymptomatic populations,
      improving quality of clinic-based health care, and research. Challenges include
      defining and reaching target populations, overcoming logistic issues, developing
      communication and counseling strategies, and determining whether alternative
      testing strategies are effectively reducing infection rates. CONCLUSIONS: The use
      of NAATs to detect CT and GC infection outside of clinic settings will
      undoubtedly continue. Future research should focus on how to best use this
      technology to reduce rates of infection.

PMID- 14695958
TI  - Are counselor demographics associated with successful human immunodeficiency
      virus/sexually transmitted disease prevention counseling?
AB  - BACKGROUND AND OBJECTIVE: HIV prevention counseling has changed behavior and
      reduced incident sexually transmitted diseases (STDs) in research participants.
      GOAL: This article assesses whether counselor demographics or counselor-client
      dyad characteristics influenced prevention counseling in Project RESPECT as
      measured by intervention completion and incident STD after counseling. STUDY
      DESIGN: We analyzed data from Project RESPECT, a randomized, controlled trial of
      HIV counseling interventions in STD clinics. RESULTS: There was no significant
      association between client failure to complete the intervention and demographic
      characteristics of the 32 counselors or dyad characteristics. Clients who did not
      complete the intervention were significantly more likely to acquire a new STD
      infection by the 12-month visit than those who completed the intervention
      (adjusted odds ratio, 1.7; confidence interval, 1.2-2.4). There was no
      significant association between new STDs and counselor characteristics or dyad
      characteristics. CONCLUSIONS: Counselor or counselor-client dyad characteristics
      evaluated in this study were not associated with intervention completion or the
      prevention of new STDs.

PMID- 14695959
TI  - Human papillomavirus prevalence and types in newborns and parents: concordance
      and modes of transmission.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this investigation was to determine the
      risk of vertical and early contact transmission of human papillomavirus (HPV) in
      newborn infants based on concordance and sequence match to HPV types in parents.
      STUDY DESIGN: The genitals of pregnant women and newborns and oral cavity of
      parents and newborns were analyzed using polymerase chain reaction and DNA
      sequencing. Data were collected about reproductive health and risk factors for
      HPV. RESULTS: Only one mother/newborn and no father/newborn pair was concordant
      for an HPV type. All other infected newborns had uninfected or discordant type
      infected parents. CONCLUSION: The risk of vertical transmission to the oral or
      genital region of newborns is rare, and transmission between parents and the
      hospitalized newborn does not appear to occur. Lack of parent/child concordance
      suggests that newborns detected with HPV in their oral cavity or genitals could
      have become infected by their mother at untested intervals during pregnancy or in
      newborns with infection in the oral cavity by other contacts after birth.

PMID- 14695960
TI  - Delivering reassurance to parents: perinatal human papillomavirus transmission is
      rare.

PMID- 14695961
TI  - Autoinoculation of human papillomavirus and vaginal transmission of human
      immunodeficiency virus: an appeal for rigorous verification.

PMID- 14695962
TI  - High prevalence of sexually transmitted diseases in young women seeking HIV
      testing in Rio de Janeiro, Brazil.
AB  - BACKGROUND AND OBJECTIVES: Few data are available on the prevalence of and risk
      factors for sexually transmitted diseases (STDs) other than HIV in Brazil. GOAL:
      The goal of this study was to determine the prevalence of HIV infection and other
      STDs in Brazilian women who seek HIV testing, investigate risk factors for these
      infections, and assess feasibility of screening in HIV test clinic settings.
      STUDY DESIGN: We conducted a cross-sectional study of 200 women, aged 14 to 29
      years, who attended an HIV testing site in central Rio de Janeiro. Participants
      completed a questionnaire and received testing for HIV, syphilis, chlamydia, and
      gonorrhea. RESULTS: HIV and other STDs were common (HIV 8%, syphilis 6.5%,
      chlamydial infection 8%, and gonorrhea 9.5%). HIV was significantly associated
      with lower education and with having an HIV-infected partner. Other STDs were
      significantly associated with younger age at first intercourse, heavy alcohol
      consumption, and marijuana use. CONCLUSION: STDs appear to be substantial health
      problems among young Brazilian women seeking HIV testing. HIV testing sites in
      Brazil should consider offering screening and treatment for STDs and substance
      abuse as part of their HIV prevention services.

PMID- 14695963
TI  - Proceedings of the 1st Latin American Erectile Dysfunction Consensus. August 28
      31, 2002. Costa do Sauipe, Brazil.

PMID- 14695964
TI  - Erectile dysfunction epidemiology.

PMID- 14695965
TI  - Anatomy and physiology of erection: pathophysiology of erectile dysfunction.

PMID- 14695966
TI  - Assessment of the patient with erectile dysfunction.

PMID- 14695967
TI  - Androgen deficiency in the aging male.

PMID- 14695968
TI  - Psychogenic erectile dysfunction and ejaculation disorders.

PMID- 14695969
TI  - Female sexual dysfunction.

PMID- 14695970
TI  - Oral drug treatment of erectile dysfunction.

PMID- 14695971
TI  - What to do when oral treatment fails?

PMID- 14695972
TI  - Erectile dysfunction: surgical treatment.

PMID- 14695973
TI  - Peyronie's disease.

PMID- 14695974
TI  - Priapism.

PMID- 14695975
TI  - Penis enlargement: current status.

PMID- 14695976
TI  - Targeted expression of human FSH receptor Asp567Gly mutant mRNA in testis of
      transgenic mice: role of human FSH receptor promoter.
AB  - AIM: To specifically express the Asp567Gly human follicle-stimulating hormone
      receptor (FSHR) under the control of its promoter to evaluate the phenotypic
      consequences in the presence of normal pituitary function. METHODS: We produced
      transgenic mice overexpressing the Asp567Gly human FSHR under the control of a
      1.5kb 5'-flanking region fragment of its promoter. RESULTS: Mice were
      phenotypically normal and fertile. In males, mRNA could be detected in the testis
      and the brain, indicating that the 1.5kb promoter fragment drives expression not
      only in the gonads. The testis weight/body weight ratio and the testosterone
      levels in transgenic and non-transgenic littermates were similar. By in situ
      hybridisation we found that the transgenic FSHR was highly expressed in Sertoli
      cells, spermatocytes and round spermatids. However, a radioligand receptor assay
      failed to show a significant difference in total FSHR binding sites in testis
      homogenates of transgenic and wild type animals, suggesting that the transgenic
      FSHR is probably not translated into functional receptor protein. CONCLUSION: A
      1.5kb 5'-region of the human FSHR drives mRNA expression of the transgene in the
      testis but leads to ectopic expression in germ cells and in the brain. No
      phenotypic consequences could be documented due to the lack of protein
      expression.

PMID- 14695977
TI  - Rodent epididymal cDNAs identified by sequence homology to human and canine
      counterparts.
AB  - AIM: Identification of the rodent counterparts of human and canine epididymal
      cDNAs HE3, HE4 and Ce8/Ly6G5C by sequence homology and analysis of their
      expression patterns and regulation level in the rat. METHODS: "Electronic
      screening" of Expressed Sequence Tag (EST) and genomic databases, followed by RT
      PCR and Northern blot analysis. RESULTS: Rodent ESTs and genomic sequences
      homologous to HE3, HE4 and Ce8/Ly6G5C were identified in the public databases and
      the "full-length" rat cDNAs cloned. To emphasise their homology to the human and
      canine genes, they were named Me3/Re3, Me4/Re4 and Re8 for mouse and rat
      counterparts, respectively. mRNA expression patterns were analysed in rats,
      including rat HE1 and HE5/CD52 counterparts as controls. Re3 and Re8 mRNAs were
      only found in the rat epididymis, while Re4 showed a broader tissue distribution.
      Within the epididymis, Re3 and Re4 mRNAs were detected in all regions; Re8, on
      the other hand, was restricted to the caput. During postnatal development, Re3
      and control mRNAs were found from the earliest stages investigated, while Re8
      mRNA was observed only from day 24 postnatum, corresponding to the onset of
      spermatogenesis in the prepubertal testis. Castration and testosterone
      supplementation of adult male rats suggested that none of the cloned mRNAs was
      directly androgen-regulated. Efferent duct ligation, however, showed that Re8
      mRNA levels depended on testicular factors other than androgens. CONCLUSION: The
      novel rodent cDNAs can now be used to monitor epididymal gene expression more
      closely and to set up various regulatory and functional studies.

PMID- 14695978
TI  - Histological study of vas deferens following intravasal laser irradiation.
AB  - AIM: To study the histologic changes of the vas deferens following Nd: YAG laser
      irradiation. METHODS: Intravasal laser irradiation was given to (i) 52 segments
      of rabbit (laser dosage: 2 seconds at 40 W approximately 50 W) and 16 segments of
      human (3 seconds at 45 W approximately 55 W) vas deferens in vitro, (ii) 25
      rabbit vasa (2 seconds approximately 2.5 seconds at 40 W approximately 45 W) in
      vivo and (iii) 2 human vasa (3 seconds at 55 W) in vivo. Segments of vasa were
      removed from the in vivo irradiated vasa deferentia 15 days approximately 180
      days (rabbit) or 15 days (man) after the exposure. All vas segments were embedded
      in methacrylate resin. Serial sections (thickness 25 microm approximately 30
      microm) were obtained and observed under a light microscope. RESULTS: (i) Laser
      induced damage reached the muscularis layer in 27% and 94% of the rabbit and
      human vas segments in vitro, respectively. (ii) Fourteen of the 25 in vivo rabbit
      vasa were completely occluded by fibrous tissue and the longer the time interval
      after treatment, the more likely was the vas occluded. Those unoccluded vasa had
      either a normal histology or a mucosal damage. (iii) One in vivo human vas was
      almost completely occluded by the fibrous tissue but the other had a relatively
      large lumen packed with sperm granulomatous tissue and partial destruction of the
      smooth muscle layer. CONCLUSION: Laser irradiation can induce long-term vas
      occlusion; for rapid occlusion, laser doses just completely destroying the
      mucosal layer will be advisable.

PMID- 14695979
TI  - Evaluation of corporal fibrosis in cadaveric pericardium and vein grafts for
      tunica albuginea substitution in rats.
AB  - AIM: To evaluate the degree of corporal fibrosis in rats with cadaveric
      pericardium or vein as grafting materials for tunica albuginea substitution.
      MATERIALS AND METHODS: Thirty male Sprague-Dawley rats (300 g approximately 325
      g) were divided at random into 3 groups of 10 animals each: group 1 was the sham
      operated controls and groups 2 and 3 underwent wedge excision of tunica albuginea
      and replacement with cadaveric pericardium and vein grafts, respectively. Four
      months later, rats were sacrificed and the penis removed to assess the degree of
      fibrosis using RT-PCR technique for TGF-bgr1 mRNA expression. The tissues were
      fixed in 10% formalin, paraffin-embedded and stained with Masson's trichrome and
      Verhoff's van Giesen for collagen and elastic fibers. RESULTS: Four months after
      grafting, there was minimal fibrosis surrounding the patch in the vein graft rats
      and moderate fibrosis in the pericardial graft rats. The degree of penile
      fibrosis in the pericardial graft rats was significantly higher than that in the
      controls (P<0.01), but in the vein graft rats it was not significantly different
      from that of the controls (P>0.05). CONCLUSION: The degree of penile fibrosis of
      cadaveric pericardial graft was significantly higher than that of the control
      group, while in the vein graft group it was comparable to the latter. The authors
      believe that the vein graft may be a more ideal substance to be used as the
      tunica albuginea substitute than the pericardial graft in the surgical treatment
      of Peyronie'S disease.

PMID- 14695980
TI  - Effect of diethylstilbestrol on polyamine metabolism in hamster epididymis.
AB  - AIM: To investigate the effect of diethylstilbestrol (DES), one of the most
      potent endocrine disruptors, on the metabolism of polyamines in hamster
      epididymis. METHODS: Male golden hamsters of 7-week-old were kept under a light
      and dark cycle of 14 h and 10 h for 1 week to stimulate maximally the gonadal
      function. DES was injected subcutaneously at doses of 0.01 mg . kg(-1) . day(-1),
      0.1 mg . kg(-1) . day(-1) and 1 mg . kg(-1) . day(-1) for one week. RESULTS: DES
      treatment caused a significant decrease in the weight of epididymis. The activity
      of epididymal ornithine decarboxylase (ODC) increased 1 day after DES treatment,
      kept at a high level for 4 days and then decreased to nearly normal level at day
      7. The activity of spermidine/spermine N1-acetyltransferase (SSAT) also increased
      transiently after DES treatment. The contents of putrescine, spermidine, spermine
      and N(1)-acetylspermidine were increased 1 day approximately 4 days after DES
      treatment and restored to normal at day 7. All these changes showed a marked
      difference between the caput and the cauda. CONCLUSION: The polyamine
      biosynthesis in the hamster epididymis can be affected by DES, a xenoestrogen.
      DES may probably affect polyamine metabolism in the epididymis by regulating the
      rate-limiting enzymes involved in the polyamine biosynthesis.

PMID- 14695981
TI  - Oestrogen-androgen crosstalk in the pathophysiology of erectile dysfunction.
AB  - Ageing in man is associated with a decline in testosterone following changes in
      the hypothalamo-pituitary-testicular axis. This may offset the physiologic
      equilibrium between oestrogen and androgen and at some point when the ratio of
      free testosterone to oestradiol reaches a critical level, the oestrogenic
      gonadotropin suppressive effect predominates with decreased release of FSH and
      LH. Adding to this endocrinal complexity is the continued peripheral conversion
      to oestradiol through aromatisation. Although the androgen deficiency is not the
      sole cause for impotence in the elderly, there is a gradual decrease in nocturnal
      penile tumescence (NPT) and spontaneous morning erections with ageing. Despite
      the age related increase in oestrogen levels, the information on the
      pathophysiological role of the "female hormone" in erectile dysfunction has been
      scanty. Together with our identification of oestrogen receptors within the penile
      cavernosum, we have delineated dysfunctional changes on male erection mediated by
      oestradiol. These findings parallel the recent concerns over environmental
      oestrogens on fertility declines in young men. Oestrogenic activity is also
      present in plants and thereby in human diet. These phytoestrogens are
      structurally and functionally similar to oestradiol and more potent than the
      environmental oestrogenic chemicals such as organochlorine and phenolic
      compounds. Thus in the light of growing concerns of possible compromising effects
      on sexuality by endogenous and environmental oestrogens, we are faced with the
      scientific need to delineate their role on the mechanism of male erectile pathway
      in health and disease for clinical correlates and prognostics.

PMID- 14695982
TI  - Human protamines and the developing spermatid: their structure, function,
      expression and relationship with male infertility.
AB  - During spermiogenesis, the protamine proteins play an integral role in spermatid
      chromatin compaction. Recent research has focused on many facets of protamine
      biology, including protamine gene and protein structure/function relationships,
      mechanisms of protamine expression regulation and involvement of the protamines
      in male fertility. In this paper, we review our current understanding of the
      structure and function of the protamine-1 (P1) and protamine-2 (P2) proteins and
      genes, the expression and regulation of these genes and the relationship between
      the protamines and male fertility. In addition, we offer a brief outlook on
      future investigation into protamine proteins.

PMID- 14695983
TI  - Male fertility following childhood cancer: current concepts and future therapies.
AB  - Prepubertal boys treated for cancer may exhibit impaired fertility in later life.
      A number of chemotherapeutic agents have been identified as being gonadotoxic,
      and certain treatment regimens, such as that used for Hodgkin's disease, are
      particularly associated with subsequent infertility. Radiotherapy may also cause
      gonadal damage, most notably following direct testicular irradiation or total
      body irradiation. Because of the varied nature of the cytotoxic insult, it can be
      difficult to predict the likelihood of infertility in later life. Currently it is
      not possible to detect gonadal damage early due to the lack of a sensitive marker
      of gonadal function in the prepubertal age group. Semen cryopreservation is
      currently the only method of preserving fertility in patients receiving
      gonadotoxic therapy. This is only applicable to postpubertal patients and can be
      problematic in the adolescent age group. At present there is no provision for the
      prepubertal boy, although there are a number of experimental methods currently
      being investigated. By harvesting testicular tissue prior to gonadotoxic therapy,
      restoration of fertility could be achieved following treatment, either by germ
      cell transplantation or by in vitro maturation of the germ cells harvested.
      Alternatively, rendering the testes quiescent during cytotoxic treatment may
      protect the germ cells from subsequent damage. In addition to the many scientific
      and technical issues to be overcome prior to clinical application of these
      techniques, a number of ethical and legal issues must also be addressed to ensure
      a safe and realistic prospect for future fertility in these patients.

PMID- 14695984
TI  - Re: Nerve sparing laparoscopic radical prostatectomy.

PMID- 14695985
TI  - Hormonal replacement therapy and aging: Asian practical recommendations on
      testosterone supplementation.
AB  - Profound and diffuse alterations in the production of gonadal and adrenal
      androgens as well as growth hormone are associated with aging. To convey this
      concept more appropriately, partial endocrine deficiency in the aging male
      (PEDAM) was introduced as a term for the phenomenon of hormonal alterations in
      the aging male. Hormones responsible for some of the manifestations associated
      with male aging are testosterone, growth hormone, dehydroepiansdrosterone (DHEA),
      melatonin, thyroid hormones and leptin. Of these, testosterone has been widely
      investigated and its beneficial and adverse effects on male bodily systems are
      relatively well established. However, a serious body of confusion and
      misunderstandings surrounding the diagnosis, treatment and monitoring of men
      suspected of having androgen deficiency has been raised. Therefore, it is timely
      to provide practical criteria for diagnosis and treatment to avoid misconception
      about the use of testosterone in the aging male. To provide an understanding and
      information of the issues, the following headings are summarized: (1) Important
      clinical consideration on testosterone supplementation in the aging male; (2)
      Asian practical recommendations on testosterone supplementation in the aging
      male.

PMID- 14695986
TI  - Effects of acupuncture and moxa treatment in patients with semen abnormalities.
AB  - AIM: To evaluate the effect of Chinese Traditional Medicine, acupuncture and moxa
      treatment, on the semen quality in patients with semen abnormalities. METHODS: In
      a prospective, controlled and blind study, nineteen patients, aged 24 years
      approximately 42 years and married for 3 years approximately 11 years without
      children with semen abnormalities in concentration, morphology and/or progressive
      motility without apparent cause, were randomized into two groups and submitted to
      acupuncture and moxa treatment at the therapeutic (Study Group) and the
      indifferent points (Control Group), respectively, for 10 weeks. Semen analyses
      were performed before and after the treatment course. RESULTS: The patients of
      the Study Group presented a significant increase in the percentage of normal-form
      sperm compared to the Control Group (calculated U=16.0, critical U=17.0).
      CONCLUSION: The Chinese Traditional Medicine acupuncture and moxa techniques
      significantly increase the percentage of normal-form sperm in infertile patients
      with oligoastenoteratozoospermia without apparent cause.

PMID- 14695987
TI  - Effect of alcoholic extract of Lepidium meyenii (Maca) on testicular function in
      male rats.
AB  - AIM: To evaluate the effect of the alcoholic extract of Lepidium meyenii (Maca)
      on the spermatogenesis in male rats. METHODS: In Holtzman rats, Maca alcoholic
      extract (5 %) was given by oral route at doses of 48 mg/day or 96 mg/day for 7
      days, 14 days and 21 days. Testicular function was assessed by measurements of
      lengths of different stages of seminiferous epithelia and by epididymal sperm
      count. RESULTS: Ethanolic extract of Maca increased the length of stages IX-XI of
      seminiferous epithelium at treatment day 7, day 14 and day 21. Progression of
      spermatogenesis was evident only after day 21 when lengths of stages XII-XIV of
      seminiferous epithelium were increased; at day 7 and day 14, no important change
      in spermatogenesis was observed. Epididymal sperm count was increased with 48
      mg/day at all times. With 96 mg/day an increase in sperm count was observed at
      day 7, but it was reduced at day 14 and day 21 of treatment. Serum testosterone
      levels were not affected. CONCLUSION: The alcoholic extract of Maca activates
      onset ant progression of spermatogenesis at 48 mg/day or 96 mg/day in rats.

PMID- 14695988
TI  - Re: 5-Fluorouracil-induced sperm shape abnormalities in rats.

PMID- 14695989
TI  - Distinct MDM2 and P14ARF expression and centrosome amplification in well
      differentiated liposarcomas.
AB  - Well-differentiated liposarcomas (WDLs) are common soft-tissue tumors in adults.
      They are characterized by large marker chromosomes and/or ring chromosomes
      containing 12q-derived sequences in which MDM2 is consistently amplified. WDLs
      are subdivided into two subtypes according to their karyotype. Type D cells
      exhibit a near-diploid karyotype, with very few or no chromosome changes. Type H
      cells exhibit a near-tetraploid karyotype and many structural changes. Expression
      of P14ARF, MDM2, and TP53 proteins was assayed in the two WDL subtypes to
      establish whether distinct expression profiles correlated with cell ploidy.
      Although a transcriptionally functional TP53 was present in most tumors
      independent of their karyotype, type H cells were characterized by high levels of
      P14ARF and MDM2 proteins. Although amplified within similar chromosome markers in
      type D tumors, MDM2 did not appear to be overexpressed. In addition, it was
      present as a C-terminal truncated protein, indicative of alternatively spliced
      variants of MDM2 mRNA. As the existence of karyotypically distinct tumors could
      result from alterations of the mitotic machinery, we investigated the centrosome
      behavior in the two WDL subtypes. Centrosome amplification occurred in WDL tumors
      types H and D independent of their ploidy status. Moreover, no functional
      centrosome difference was found between the two tumor subtypes.

PMID- 14695990
TI  - A novel gene, FGA7, is fused to RUNX1/AML1 in a t(4;21)(q28;q22) in a patient
      with T-cell acute lymphoblastic leukemia.
AB  - AML1 is among the most frequent targets of chromosomal rearrangements in human
      leukemias. We report here the molecular analysis of a t(4;21)(q28;q22) that has
      disrupted AML1 in a patient with de novo T-cell acute lymphoblastic leukemia. By
      using 3'-RACE analysis, we show that this rearrangement results in the fusion of
      a novel gene immediately downstream of exon 5 or exon 6 of AML1, indicating that
      the AML1 breakpoint lies in intron 6 and that alternative fusion splice variants
      are generated. The sequence of the novel gene, located at 4q28, does not have any
      significant homology with any of the known genes in the human GenBank DNA
      database. However, the first 118 bases are identical to a part of a human ovarian
      EST. Also, its high homology with mouse and rat sequences suggests that this
      sequence most probably represents a part of a novel gene, which we named FGA7
      (Fused Gene 7 to AML1). Following the AML1 open reading frame, the FGA7 sequence
      encodes an unknown protein of 27 amino acids. We isolated three bacterial
      artificial chromosome (BAC) clones that contain the FGA7 sequence and confirmed
      the breakpoint of the gene on the patient's metaphase spreads by fluorescence in
      situ hybridization using these BACs as probes. RT-PCR and Northern blot analyses
      revealed that FGA7 is expressed in ovarian and skeletal muscle tissues. The
      predicted AML1-FGA7 chimeric proteins contained a limited number of residues
      fused to AML1 in a situation similar to that reported for the AML1-EAP fusion
      that is a product of t(3;21). It is possible that the expression of a
      constitutively shortened AML1 could compete with full-length AML1 and act as a
      dominant negative inhibitor of the promoters that the core binding factor
      activates.

PMID- 14695991
TI  - Mutational analysis of susceptibility genes RNASEL/HPC1, ELAC2/HPC2, and MSR1 in
      sporadic prostate cancer.
AB  - Three putative prostate cancer-susceptibility genes, RNASEL/HPC1 at 1q24, MSR1 at
      8p22, and ELAC2/HPC2 at 17p11, have recently been identified. Our objective was
      to investigate somatic mutations in these genes in sporadic prostate cancer. We
      analyzed 39 clinical prostate cancer specimens, 10 prostate cancer xenografts
      (LuCaP series), and 4 prostate cancer cell lines (LNCaP, DU145, PC-3, and MPC-3)
      for genetic changes using denaturing high-performance liquid chromatography and
      direct sequencing in order to screen the whole coding regions of RNASEL and MSR1,
      as well as exons 7 and 17 of ELAC2. The known 471delAAAG truncating mutation was
      found in the RNASEL gene in cell line LNCaP. The only new missense variation in
      RNASEL, Gly296Val, was found in cell line DU145, but not in any other samples.
      RNASEL and ELAC2 also showed the common missense polymorphic changes. A
      previously reported truncating mutation (Arg293X) was found in MSR1 in the germ
      line of one individual. Our results indicate that inactivation of the RNASEL,
      ELAC2, or MSR1 genes by somatic mutation is a rare phenomenon in sporadic
      prostate cancer.

PMID- 14695992
TI  - Amplification and overexpression of the IGF2 regulator PLAG1 in hepatoblastoma.
AB  - There is evidence that 8q amplification is associated with poor prognosis in
      hepatoblastoma. A previous comparative genomic hybridization analysis identified
      a critical region in chromosomal bands 8q11.2-q13. Using restriction landmark
      genomic scanning in combination with a virtual genome scan, we showed that this
      region is delineated by sequences within contig NT_008183 of chromosomal subbands
      8q11.22-q11.23. A real-time PCR-based genomic copy number assay of 20
      hepatoblastomas revealed gain or amplification in this critical chromosomal
      region in eight tumors. The expression of four genes and expressed sequence tags
      (ESTs) within this newly defined region was assayed by real-time reverse
      transcriptase polymerase chain reaction (RT-PCR) in four tumors with and six
      tumors without gain or amplification. The PLAG1 oncogene was found to be highly
      expressed in all but one tumor compared to normal liver tissue. Furthermore,
      quantitative RT-PCR revealed that the expression level of the developmentally
      regulated transcription factor PLAG1 was 3-12 times greater in hepatoblastoma
      tumors and cell lines compared to age-matched normal liver and comparable to the
      expression in fetal liver tissue. PLAG1 has been shown be a transcriptional
      activator of IGF2 in other tumor types. Using luciferase reporter assays, we
      demonstrated that PLAG1 transactivates transcription from the embryonic IGF2
      promoter P3, also in hepatoblastoma cell lines. Thus, our results provide
      evidence that PLAG1 overexpression may be responsible for the frequently observed
      up-regulation of IGF2 in hepatoblastoma and therefore may be implicated in the
      molecular pathogenesis of this childhood neoplasia.

PMID- 14695993
TI  - Activated BRAF targets proximal colon tumors with mismatch repair deficiency and
      MLH1 inactivation.
AB  - BRAF, a serine/threonine kinase of the RAF family, is a downstream transducer of
      the RAS-regulated MAPK pathway and signals upstream of MEK1/2 kinases. Recently,
      activating mutations within BRAF have been reported in a high percentage of
      melanomas and colorectal carcinomas and shown to have oncogenic capabilities.
      Further, their association to mismatch-repair-deficient tumors has suggested the
      involvement of the RAS/RAF pathway in the tumorigenesis of microsatellite
      unstable colon cancers, and that RAS and RAF mutations are alternative genetic
      events. We determined whether colorectal mismatch-repair-deficient tumors with
      BRAF mutations show a specific genotype when compared with tumors with wild-type
      BRAF, and whether they can be associated with a particular clinicopathological
      feature. Here, we report a striking association of BRAF, but not of APC, KRAS2,
      AXIN2, and TP53 mutations, with proximal mismatch-repair-deficient colon tumors
      and MLH1 hypermethylation. Our results support the hypothesis that proximal and
      distal colorectal tumors with mismatch repair deficiency harbor different genetic
      alterations, and we suggest that the involvement of the RAS/RAF pathway in
      colorectal tumorigenesis is differentially modulated according to tumor location
      and MLH1 inactivation.

PMID- 14695994
TI  - Variety and complexity of chromosome 17 translocations in neuroblastoma.
AB  - In neuroblastoma, the most frequent genetic alteration is gain of chromosome arm
      17q, which arises from unbalanced translocations. To document these genetic
      events more precisely, we performed an extensive study of chromosome 17
      breakpoints in 27 neuroblastoma cell lines by using a combination of fluorescence
      in situ hybridization mapping with BAC/PAC clones and allele analysis with
      polymorphic markers. All cases exhibited one or more unbalanced chromosome 17
      translocations, and 15 distinct breakpoint regions could be mapped. This high
      variability indicates that gene fusion or disruption events are extremely
      unlikely to account for the underlying oncogenic role of these translocations.
      However, breakpoints were not randomly distributed, most of them mapping to the
      proximal part of 17q. As a result of translocations, all cell lines but one
      exhibited gain of the 53.5 Mb-->qter fragment, bordered proximally by the clone
      CTC-462L7. The most telomeric breakpoint, flanked by the clone RP11-443M10,
      defined the 70.9 Mb-->qter fragment as a region of additional gain. In addition
      to chromosome gains, loss of heterozygosity for the short arm of chromosome 17
      was observed in close to half the cases. It was either related to a chromosome 17
      monosomy or to a uniparental isodisomy. Finally, in cases with a single normal
      chromosome 17, we show that the parental origin of the translocated chromosome 17
      can be either distinct or identical to that of the normal chromosome. Similarly,
      multiple translocations within the same cell line can either involve the same or
      different chromosome 17 homologues, indicating the likely absence of parental
      origin bias in the generation of these alterations.

PMID- 14695995
TI  - Translocation t(11;14) in multiple myeloma: Analysis of translocation breakpoints
      on der(11) and der(14) chromosomes suggests complex molecular mechanisms of
      recombination.
AB  - We describe the characterization of the genomic DNA breakpoints of two multiple
      myeloma (MM) patients with t(11;14). IGH translocation events are present in many
      MM tumors, and it is proposed that they occur early in the pathogenesis, based on
      the assumption that the translocations are simple reciprocal events mediated by
      errors in class-switch recombination (CSR). We provide evidence from two patients
      that the translocation event can be more complex, with DNA from chromosome band
      11q13 joined to apparently already recombined hybrid (Smu/Sgamma) switch region
      sequences. In one case, there was also evidence that a further rearrangement had
      occurred at the t(11;14) recombination site, resulting in an inversion of 40 bp
      of the 5'Smu flanking sequence. This suggests that primary IGH arrangements in MM
      may be more complex than previous myeloma models have suggested, but that they
      essentially occur through illegitimate CSR events.

PMID- 14695996
TI  - Clonal variation of the immunogenotype in relapsed ETV6/RUNX1-positive acute
      lymphoblastic leukemia indicates subclone formation during early stages of
      leukemia development.
AB  - Recent data suggest that late relapses evolve from an ancestral ETV6/RUNX1
      positive (also designated TEL/AML1-positive) clone resulting from secondary
      changes (ETV6 deletion) that differ from those of the initial leukemia and, as a
      consequence, may also deviate in their clonotypic immunoglobulin/T-cell receptor
      (IG/TCR) gene rearrangements. The aim of our study was to compare the
      immunogenotype and fluorescence in situ hybridization (FISH) patterns of the
      unrearranged ETV6 allele of matched diagnosis/relapse samples from 12 children
      with an early or late relapse. We identified varying degrees of differences in
      the IG/TCR in six of them. A clonal change or evolution of the unrearranged ETV6
      allele was also observed in six children but remained unchanged in three.
      However, these two parameters were not in concordance, nor did the immunogenotype
      pattern correlate with the duration of the first remission. We therefore propose
      that the potential of the immunogenotype to diversify depends primarily on the
      stage of IG/TCR gene configuration of the cell in which the ETV6/RUNX1 gene
      fusion takes place.

PMID- 14695997
TI  - Germ-line ATM gene alterations are associated with susceptibility to sporadic T
      cell acute lymphoblastic leukemia in children.
AB  - A major feature of ataxia-telangiectasia (A-T) is an increased risk of cancer,
      particularly of lymphoid malignancies. We studied ATM gene involvement in
      leukemic cells derived from 39 pediatric T-cell acute lymphoblastic leukemias
      (ALLs). Two types of sequence changes--truncating and missense--were identified
      in 8 T-cell ALL samples: 3 truncating changes, all previously identified in A-T
      (R35X, -30del215, 2284delCT), and 3 missense variants (V410A, F582L, F1463C) were
      found, none associated with loss of heterozygosity (LOH). In all patients
      studied, the mutation was present in the germ-line. A-T carriers, defined by the
      finding of truncating mutations, were found to be 12.9 times more frequent than
      in the normal population (P = 0.004). A normally ethnically matched population
      was screened for the 3 missense variants, and their frequency was significantly
      more prevalent (4.9-fold excess) than in the normal population (P = 0.03). Our
      data suggest there is some evidence of an association between missense
      alterations in the ATM gene and T-cell ALL. A significant difference in the mean
      age at diagnosis of T-cell ALL was noted between patients harboring an ATM
      sequence change and those with no change, 5.4 years and 9.7 years, respectively
      (P = 0.001). No ATM alterations were identified in relapse samples, indicating
      that ATM does not play a role in disease progression. The high prevalence of germ
      line truncating and missense ATM gene alterations among children with sporadic T
      cell ALL suggests an association with susceptibility to T-cell acute leukemia and
      supports the model of predisposition to cancer in A-T heterozygotes.

PMID- 14695998
TI  - High expression of precursor microRNA-155/BIC RNA in children with Burkitt
      lymphoma.

PMID- 14696002
TI  - Animal anaesthesia for in vivo magnetic resonance.
AB  - Almost all animal patients, including research subjects, presented for MRI/MRS
      studies are anesthetized. As MR moves rapidly beyond simple anatomic studies,
      becoming a powerful tool for defining physiologic processes, it is imperative
      that investigators become familiar with the physiologic effects of the
      anaesthetic drugs. This decreases confounding variables, making data
      interpretation more accurate and more applicable to future uses. This article is
      intended to be a basic resource for investigators wishing to increase their
      understanding of the anesthetic drugs. The following is a general discussion
      describing the mechanism of action and physiologic effects of the more common
      anaesthetic drugs used in laboratory animals. A dosing table of common
      anaesthetics and analgesics used in mice and rats is included because these two
      species comprise a great majority of MRI/MRS research subjects.

PMID- 14696003
TI  - The apparent dependence of the diffusion coefficient of N-acetylaspartate upon
      magnetic field strength: evidence of an interaction with NMR methodology.
AB  - An inverse relationship between applied magnetic field strength and the apparent
      diffusion coefficient (ADC) of several important brain metabolites including N
      acetyl-l-aspartate (NAA), choline and creatine, measured in vivo using proton
      magnetic resonance spectroscopy (MRS), has been reported. In this investigation,
      using phantom studies of NAA at magnetic field strengths of 3 and 7 T, these
      observations have been verified under controlled MRS conditions in vitro, and the
      ADC of NAA has been found to vary inversely with magnetic field strength,
      decreasing at a rate of 2.5%/T at 20 degrees C. We have also assessed whether the
      effect is a function of a systemic bias in methodology, or if the effect is
      actually on the rate of molecular diffusion. This was done using an MRS
      independent method for measurement of molecular diffusion in NAA phantoms at 0,
      0.025 and 7 T applied magnetic field strengths. As a result, it has been
      demonstrated that the observed apparent magnetic field dependence of the ADC of
      NAA is a consequence of the NMR measurement and is apparently not a real effect
      on molecular diffusion.

PMID- 14696004
TI  - MRCP in the diagnosis of iatrogenic bile duct injury.
AB  - Postoperative biliary tract lesions are becoming increasingly common. The
      diagnosis is made by direct cholangiography via endoscopic retrograde
      cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography
      (PTC). The present comparative study evaluates the diagnostic efficacy of
      magnetic resonance cholangiopancreatography (MRCP) in application to iatrogenic
      bile duct injury. A prospective blind study was performed, contrasting MRCP and
      ERCP in 10 patients with suspected postoperative biliary tract lesions. MRCP was
      performed less than 72 h before ERCP. Final diagnosis was made on the basis of
      findings at surgery and ERCP. The presence of biliary dilatation, excision
      injury, stricture, fluid collection and free fluid was analyzed. The mean patient
      age was 66.5 years. There were three males and seven females. The type of
      postoperative lesion (Bergman classification) are five patients type C, three
      type D, one type B and one type A. Diagnostic failure was recorded in two cases
      with ERCP, while in five patients it was unable to define a therapeutic approach.
      In contrast, MRCP correctly diagnosed all patients. MRCP is effective in
      diagnosing postoperative biliary tract lesions, and can help decide the best
      therapeutic approach.

PMID- 14696005
TI  - Order parameters of the orientation distribution of collagen fibers in Achilles
      tendon by 1H NMR of multipolar spin states.
AB  - The angular distribution function of collagen fibrils in a sheep Achilles tendon
      was investigated by (1)H NMR of multipolar spin states represented by dipolar
      encoded longitudinal magnetization and double-quantum filtered signals. For the
      first time the angular distribution function based on the Legendre moment
      expansion is used. Order parameters were obtained from the anisotropy of (1)H
      residual dipolar couplings of bond water, which were determined model-free from
      the excitation efficiency of the multipolar spin states and from double-quantum
      filtered line splitting. The orientation distribution function of collagen
      fibrils in Achilles tendon measured from the anisotropy of the residual dipolar
      couplings is characterized by the average values of beta0 = 1.8+/-0.2 degrees and
      order parameters [P2] = 0.93+/-0.04, [P4] = 0.78+/-0.04 and [P6] = 0.58+/-0.04.
      The order of many biological tissues in the presence of ageing, injuries or
      regeneration can be quantified by the order parameters of the angular
      distribution function.

PMID- 14696006
TI  - In-vivo high resolution three-dimensional MRI studies of rat joints at 7 T.
AB  - It is important to obtain high resolution images of joints for the study of
      disease, especially in rodent experimental models. We optimized (1)H magnetic
      resonance imaging three-dimensional sequences at 7 T, with lipid signal
      suppression, and T(1) and T(2) measurements for in-vivo experiments on rat
      joints, in order to assess the effectiveness of high-field MRI. The method was
      validated by applying it to the early diagnosis of arthritis. We studied the
      progress of rheumatoid arthritis in an arthritic rat model. We observed the rats'
      knees for 21 days after inducing arthritis. The images acquired over one hour had
      a high resolution of 1.75 x 10(-3) mm(3), (105 x 105 x 145 microm(3)) which
      allowed us to spot the early stages of joint degeneration, such as bone erosion,
      and to observe an apparent 'MRI' loss of cartilage thickness, attributed to
      dehydration of the cartilage tissue. The MR images obtained during the early
      stages of rheumatoid arthritis enabled us to study joint changes accurately
      before any histological signs of attack were visible.

PMID- 14696007
TI  - Tissue-specific differences in 2-fluoro-2-deoxyglucose metabolism beyond FDG-6-P:
      a 19F NMR spectroscopy study in the rat.
AB  - 2-Fluoro-[(18)F]-2-deoxy-glucose (FDG) is a positron-emitting analogue of glucose
      used clinically in positron emission tomography (PET) to assess glucose
      utilization in diseased and healthy tissue. Originally developed to measure local
      cerebral glucose utilization rates, it has now found applications in tumour
      diagnosis and in the study of myocardial glucose uptake. Once taken up into the
      cell, FDG is phosphorylated to FDG-6-phosphate (FDG-6-P) by hexokinase and was
      originally believed to be trapped as a terminal metabolite. This 'metabolic
      trapping' of FDG-6-P forms the basis of the analysis of PET data. In this study,
      we have used (19)F NMR spectroscopy to investigate FDG metabolism following the
      injection of a bolus of the glucose tracer into the rat (n=6). Ninety minutes
      after the (19)FDG injection, the brain, heart, liver and kidneys were removed and
      the (19)FDG metabolites in each were extracted and quantified. We report that
      significant metabolism of FDG occurs beyond FDG-6-P in all organs examined and
      that the extent of this metabolism varies from tissue to tissue (degree of
      metabolism beyond FDG-6-P, expressed as percentage of total organ FDG content,
      was brain 45 +/- 3%; heart 29 +/- 2%; liver 22+/-3% and kidney 17 +/- 3%, mean +/
      SEM n=6). Furthermore, we demonstrate that the relative accumulation of each
      metabolite was tissue-dependent and reflected the metabolic and regulatory
      characteristics of each organ. Such inter-tissue differences may have
      implications for the mathematical modelling of glucose uptake and phosphorylation
      using FDG as a glucose tracer.

PMID- 14696008
TI  - Proton T1 relaxation times of cerebral metabolites differ within and between
      regions of normal human brain.
AB  - Saturation recovery spectra (STEAM) were acquired at 1.5 T with 7 TRs ranging
      from 530 to 5000 ms and a constant TE of 30 ms in voxels (7.2 ml) located in
      occipital grey, parietal white and frontal white matter (10 subjects each
      location). Spectra were also acquired at 7, 21 and 37 degrees C from separate 100
      mm solutions of inositol (Ins), choline-containing compounds (Cho), N-acetyl
      aspartate (NAA) and creatine. Simulations of T(1) fits with 2, 3 and 7 TRs
      demonstrated that at typical SNR there is potential for both inaccurate and
      biased results. In vivo, different metabolites had significantly different T(1)s
      within the same brain volume. The same order from shortest to longest T(1) (Ins,
      Cho, NAA, creatine) was found for all three brain regions. The order (Ins, NAA,
      creatine, Cho) was found in the metabolite solutions and was consistent with a
      simple model in which T(1) is inversely proportional to molecular weight. For all
      individual metabolites, T(1) increased from occipital grey to parietal white to
      frontal white matter. This study demonstrates that, in spectra acquired with TR
      near 1 s, T(1) weightings are substantially different for metabolites within a
      single tissue and also for the same metabolites in different tissues.

PMID- 14696009
TI  - Loss of nicotine-induced behavioral sensitization in micro-opioid receptor
      knockout mice.
AB  - Repeated administration of nicotine produces behavioral sensitization. However,
      the possible mechanism of behavioral sensitization to nicotine remains unclear.
      The present study was undertaken in micro-opioid receptor knockout mice, to
      examine the hypothesis that micro-opioid receptors play a crucial role in
      behavioral sensitization to nicotine. All mice received saline or nicotine (0.05
      mg/kg, s.c) twice a day for 7 consecutive days. The mice remained drug free for 3
      days and on day 11 each group was challenged with saline or nicotine (0.05 mg/kg,
      s.c.). On day 1, it was observed that the single injection of nicotine (0.05
      mg/kg, s.c.) did not influence locomotor activity in either micro-opioid receptor
      knockout or in wildtype mice. On day 7 (24 h after mice had been treated twice
      daily for 6 consecutive days with an injection of 0.05 mg/kg of nicotine), the
      mice were challenged with a single injection of nicotine, which produced
      behavioral sensitization in the wildtype but not in micro-opioid receptor
      knockout mice. On day 11, following 3 days of withdrawal after the second
      injection of nicotine on day 7, nicotine-treated mice were challenged with a
      single injection of nicotine and showed the behavioral sensitization of wildtype.
      However, nicotine challenge did not induce behavioral sensitization in micro
      opioid receptor knockout mice. Our data indicate that a lack of micro-opioid
      receptors can inhibit the effects of nicotine-induced behavioral sensitization.
      This result strongly suggests that the micro-opioid receptor plays an important
      role in behavioral sensitization to nicotine.

PMID- 14696010
TI  - Nerve terminal glutamate immunoreactivity in the rat nucleus accumbens and
      ventral tegmental area after a short withdrawal from cocaine.
AB  - Cocaine administration has been shown to alter glutamate transmission in numerous
      studies. Using quantitative electron microscopic immunogold labeling, our
      laboratory has previously reported that nerve terminal glutamate immunoreactivity
      is transiently altered following cocaine administration. The present study was
      undertaken to examine presynaptic nerve terminal glutamate immunoreactivity at
      shorter time points after withdrawal from cocaine. Animals received saline or
      cocaine for 7 days followed 3 days later by a cocaine or saline challenge. Most
      (>75%) cocaine-challenged animals had a heightened locomotor response to cocaine
      compared to the first day of cocaine and were considered behaviorally sensitized.
      One day after the challenge, glutamate immunogold-labeling was quantified in
      nerve terminals making asymmetrical synaptic contacts within the core and shell
      of the nucleus accumbens and ventral tegmental area. A single dose of cocaine did
      not alter the density of presynaptic nerve terminal glutamate immunoreactivity in
      the nucleus accumbens (NAc) or ventral tegmental area (VTA). The density of nerve
      terminal glutamate immunoreactivity in the shell, but not the core, was
      significantly increased in the animals receiving repeated cocaine. In the VTA the
      density of nerve terminal glutamate immunoreactivity did not change in the
      cocaine-sensitized group, but was significantly increased in the nonsensitized
      group. The finding that repeated cocaine treatment increased glutamate nerve
      terminal immunolabeling within the nucleus accumbens shell, but not the core,
      supports the hypothesis that glutamate synapses in the core and shell are
      differentially sensitive to repeated cocaine administration. Overall, our study
      does not support a role for changes in presynaptic glutamate in the development
      of behavioral sensitization.

PMID- 14696011
TI  - Clozapine and dopamine D3 receptor antisense reduce cocaine- and amphetamine
      regulated transcript expression in the rat nucleus accumbens shell.
AB  - Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide highly
      expressed in the hypothalamus and nucleus accumbens. Hypothalamic CART has been
      associated with food intake and body weight control, but in the nucleus accumbens
      the role of CART remains elusive. New generations of antipsychotic drugs show a
      good efficacy over psychotic symptoms but they induce an important weight gain.
      The mechanism underlying this unexpected side effect is still unknown. The
      present results show, for the first time, that acute and chronic treatment with
      the atypical neuroleptic clozapine, but not the conventional neuroleptic
      haloperidol, reduced the expression of CART mRNA in the shell of the nucleus
      accumbens. CART mRNA is colocalized with both dopamine D(2) and D(3) receptor
      transcripts in the nucleus accumbens shell. However, a dopamine D(3) receptor,
      but not D(2), antisense oligonucleotide administration reduced CART expression in
      this brain area. These results suggest that the dopamine D(3) receptor, but not
      the D(2), is involved in the control of CART expression in the nucleus accumbens
      and that it may participate in the modulation of CART mRNA levels by clozapine.
      The modulation of CART, an anorexigenic neuropeptide, in the dopamine mesolimbic
      pathway may potentially play a role in dysregulated food intake induced by some
      antipsychotic drugs.

PMID- 14696012
TI  - Changes in PKA activity and Gs alpha and Golf alpha levels after amphetamine- and
      cocaine-induced behavioral sensitization.
AB  - Neuroadaptations in the cAMP signal transduction system have been proposed to
      play a critical role in psychostimulant-induced behavioral sensitization. Studies
      relevant to this hypothesis have provided conflicting evidence, however, because
      repeated cocaine and amphetamine treatment has been alternately reported to
      either increase or decrease protein kinase A (PKA) activity in the nucleus
      accumbens and dorsal striatum. In an attempt to reconcile these disparate
      findings, PKA activity and the stimulatory G-protein subunits, G(salpha) and
      G(olfalpha), were measured after rats had received a sensitization-inducing
      regimen of amphetamine or cocaine. Results showed that seven consecutive daily
      injections of amphetamine or cocaine produced locomotor sensitization and caused
      a reduction in accumbal PKA activity. A challenge injection of amphetamine on the
      test day also reduced dorsal striatal PKA activity. G(salpha) levels were
      unaffected by psychostimulant exposure, while G(olfalpha) levels in the nucleus
      accumbens declined significantly after amphetamine or cocaine pretreatment.
      Because repeated amphetamine and cocaine treatment both induced behavioral
      sensitization and decreased accumbal PKA activity, it appears that
      psychostimulant-induced increases in PKA activity are not necessary for the
      ultimate expression of behavioral sensitization.

PMID- 14696013
TI  - Detailed distribution of neuropeptide FF receptors (NPFF1 and NPFF2) in the rat,
      mouse, octodon, rabbit, guinea pig, and marmoset monkey brains: a comparative
      autoradiographic study.
AB  - The distribution of neuropeptide FF receptors (NPFF(1) and NPFF(2)) was analyzed
      throughout the central nervous system of rodents (rat, mouse, Octodon degus, and
      guinea pig), rabbit, and marmoset monkey brains, representing three orders of
      mammals. Quantitative in vitro receptor autoradiography with [(125)I]EYF
      ([(125)I]EYWSLAAPQRF-NH(2)) and [(125)I]YVP ([(125)I]YVPNLPQRF-NH(2)) as specific
      radioligands for NPFF(2) and NPFF(1) receptors, respectively, was used. The
      NPFF(2) receptor is predominantly expressed in all species, except in the central
      nervous system of Octodon degus, in which it is undetectable. The density of the
      NPFF(1) subtype is low in rat and mice, moderate in octodon, rabbit, and monkey,
      and relatively high in the guinea pig. The present study reveals prominent
      species differences in the NPFF receptors expression in the brain. The
      distribution pattern of NPFF(2) receptors in the diencephalon and the superficial
      layers of the spinal cord is consistent with a hypothesized potential role for
      NPFF in the modulation of sensory input and opioid analgesia. In contrast, the
      constant presence of NPFF(1) receptors in the septum, the nucleus of the tractus
      solitarius, and the hypothalamus suggest its participation in neuroendocrine
      functions.

PMID- 14696014
TI  - Electric fields of synaptic currents could influence diffusion of charged
      neurotransmitter molecules.
AB  - Rapid activation of synaptic receptor-channels evokes an ion current that flows
      through the narrow synaptic cleft; this exerts a significant voltage drop and
      therefore strong electric field (10(4) V/m range) directed towards the current
      sinks in the cleft. To what extent this field affects fast diffusion of charged
      neurotransmitter molecules is not known. We draw a theoretical framework for this
      complex electrodiffusion phenomenon and establish the basic relationships between
      the synaptic current and the time course of neurotransmitter in the cleft. The
      analyses predict that excitatory currents could significantly accelerate the
      dispersion of negatively charged molecules from the cleft while attracting the
      positively charged molecules towards the current sinks. This previously
      unrecognized mechanism should affect the kinetics of synaptic receptor currents,
      thus contributing to fast synaptic signaling in the brain.

PMID- 14696015
TI  - Gene expression profiling in the midbrain of striatal 6-hydroxydopamine-injected
      mice.
AB  - In order to clarify mechanisms underlying dopaminergic neuronal death in
      Parkinson's disease (PD), a gene expression profiling study was performed in a
      rodent model of PD. In this model, mice are intrastriatally injected with 6
      hydroxydopamine (6-OHDA) and dopaminergic neurons in the substantia nigra (SN)
      gradually die by retrograde degeneration. The SN were removed 2 h, 24 h, or 14
      days after 6-OHDA administration. Levels of mRNAs related to cell death or
      survival were quantified using adaptor-tagged competitive PCR (ATAC-PCR). The
      cyclin D1 gene showed an immediate increase in mRNA expression. After 24 h, when
      dopaminergic neurons were under intense degeneration, levels of caspase 8 mRNA
      and p53 apoptosis effecter related to pmp 22 (PERP) mRNA increased and,
      conversely, FAS mRNA decreased. After 14 days, when the degeneration was
      attenuated, levels of PERP mRNA and serum- and glucocorticoid-regulated kinase
      (SGK) mRNA still increased. SGK has a similarity to AKT, which is an important
      molecule involved in nerve growth factor signal transduction. AKT mRNA levels are
      low in dopaminergic neurons. These results suggest that an increase in cyclin D1
      mRNA triggers dopaminergic neurons to enter an abnormal cell cycle, which leads
      to neuronal degeneration and cell death, possibly induced by PERP and caspase 8.
      In addition to cell death-related genes, several survival-related genes are
      activated. SGK might function as a key enzyme for the survival of dopaminergic
      neurons.

PMID- 14696016
TI  - Lesion of subthalamic or motor thalamic nucleus in 6-hydroxydopamine-treated
      rats: effects on striatal glutamate and apomorphine-induced contralateral
      rotations.
AB  - A unilateral lesion of the rat nigrostriatal pathway with 6-hydroxydopamine (6
      OHDA) results in a decrease in the basal extracellular level of striatal
      glutamate, a nearly complete loss of tyrosine hydroxylase (TH) immunolabeling, an
      increase in the density of glutamate immunogold labeling within nerve terminals
      making an asymmetrical synaptic contact, and an increase in the number of
      apomorphine-induced contralateral rotations. [Meshul et al. (1999) Neuroscience
      88:1-16; Meshul and Allen (2000) Synapse 36:129-142]. In Parkinson's disease, a
      lesion of either the subthalamic nucleus (STN) or the motor thalamic nucleus
      relieves the patient of some of the motor difficulties associated with this
      disorder. In this rodent model, either the STN or motor thalamic nucleus was
      electrolytically destroyed 2 months following a unilateral 6-OHDA lesions.
      Following a lesion of either the STN or motor thalamic nucleus in 6-OHDA-treated
      rats, there was a significant decrease (40-60%) in the number of apomorphine
      induced contralateral rotations compared to the 6-OHDA group. There was a
      significant decrease (<30%) in the basal extracellular level of striatal
      glutamate in all of the experimental groups compared to the sham group. Following
      an STN and/or 6-OHDA lesion, the decrease in striatal extracellular levels was
      inversely associated with an increase in the density of nerve terminal glutamate
      immunolabeling. There was no change in nerve terminal glutamate immunogold
      labeling in either the motor thalamic or motor thalamic plus 6-OHDA lesion groups
      compared to the sham group. The decrease in the number of apomorphine-induced
      rotations was not due to an increase in TH immunolabeling (i.e., sprouting)
      within the denervated striatum. This suggests that alterations in striatal
      glutamate appear not to be directly involved in the STN or motor thalamic lesion
      induced reduction in contralateral rotations.

PMID- 14696017
TI  - Atypical antipsychotics and diabetic propensity: more questions than answers?

PMID- 14696018
TI  - Milnacipran and pindolol: a randomized trial of reduction of antidepressant
      latency.
AB  - BACKGROUND: New, better tolerated and faster treatments for depression are
      needed. Patients are understandably unhappy with having to wait 3 to 4 weeks for
      a response to an antidepressant, while experiencing side effects almost
      immediately. This frequently has an adverse effect on compliance and engagement
      with treatment. AIMS: The primary objective was to assess the activity of
      pindolol on the onset of antidepressive response of milnacipran. The secondary
      objective was to assess the number of responders among the patients who received
      milnacipran and pindolol versus patients who received milnacipran and placebo.
      The tertiary objective was to evaluate the safety of milnacipran and pindolol
      versus milnacipran and placebo. METHOD: Randomized, double-blind, placebo
      controlled study over 42 days. SETTING: Inner city London community mental health
      teams. PARTICIPANTS: 80 patients were selected and gave written consent to
      treatment, 78 were randomized (39 in each group) and evaluated for safety
      (intention-to-treat, ITT, safety data set), 77 (ITT efficacy data set), and 64
      (per protocol, PP, data set) were evaluated for efficacy. The mean age was 31.9
      for the pindolol group and 32.3 for the placebo. INTERVENTION: All patients
      received milnacipran 50 mg twice a day plus either pindolol 2.5 mg (the 'pindolol
      group') or matching placebo (the 'placebo group') three times a day. OUTCOME
      MEASURES: The main efficacy variable was the Montgomery-Asberg depression rating
      scale (MADRS) score at days 0, 4, 7, 10, 14, 21, 28, 42 on PP data set in an
      observation carried (OC) approach. Secondary efficacy variables were clinical
      global impression (global improvement) and Hamilton depression rating scale
      (HDRS). RESULTS: Improvement in MADRS total score was greater in the pindolol
      group than in the placebo group from day 7 (p=0.03). Responder rates in the
      clinical global impression were 97.2% for the pindolol group and 60.6% for the
      placebo group. The treatment was well tolerated with the most common side effects
      being nausea (28.2%; 35.9%), vomiting (7.7%; 23.1%), hot flushes (15.4%; 5.1%)
      and sweating (12.8%; 12.8%). CONCLUSION: The milnacipran and pindolol combination
      is safe, well tolerated and efficacious in major depression, and represents a
      rational strategy for the possible acceleration or potentiation of antidepressant
      action.

PMID- 14696019
TI  - Cross-cultural validation of the Leeds sleep evaluation questionnaire (LSEQ) in
      insomnia patients.
AB  - The Leeds sleep evaluation questionnaire (LSEQ) is a standardized self-reporting
      instrument comprising ten 100 mm visual analogue scales that pertain to the ease
      of getting to sleep (GTS), quality of sleep (QOS), ease of awakening from sleep
      (AFS) and alertness and behaviour following wakefulness (BFW). Although the LSEQ
      has been used in a variety of populations, published psychometric data on
      insomnia patients are limited. The LSEQ reliability and construct validity was
      evaluated in 396 French insomnia patients aged 55 years and over, who were
      treated with placebo (2 weeks) and melatonin (3 weeks). The results supported
      LSEQ internal consistency, reliability and construct validity with minor
      differences from those of the original English version. Then the internal
      consistency of the LSEQ was evaluated in 257 insomnia patients (age 20-80 years)
      in France and Israel who, following a 1 week placebo baseline, were randomized to
      placebo or melatonin treatment for 3 weeks. Cronbach's alpha and Pearson's r
      correlation coefficients for placebo and drug treatment conditions (p<0.001 for
      all) supported LSEQ internal consistency in different treatment and age groups
      and in different languages. It is concluded that the consistency, reliability and
      validity of the four LSEQ domains allows them to be singled out as independent
      outcome variables in cross cultural sleep research and clinical practice in adult
      and elderly patients with insomnia.

PMID- 14696020
TI  - Comparative study of acute effects of single doses of fexofenadine, olopatadine,
      d-chlorpheniramine and placebo on psychomotor function in healthy volunteers.
AB  - Since most classical (first-generation) antihistamines have undesirable sedative
      effects on the central nervous system (CNS), newer (second-generation)
      antihistamines have been developed to relieve the sedative effects and to improve
      the patient's quality of life. However, the psychomotor profiles of second
      generation antihistamines are not fully elucidated. In this randomized, double
      blind, crossover study, the acute effects of single doses of second-generation
      antihistamines, fexofenadine (120 mg) and olopatadine (10 mg), on cognitive and
      psychomotor performance were investigated in comparison with those of placebo and
      d-chlorpheniramine (4 mg), a first-generation antihistamine, using objective and
      subjective assessments, in 11 healthy Japanese volunteers. In a battery of
      psychomotor tests, d-chlorpheniramine impaired tracking ability in the
      compensatory tracking task and caused a reduction in behavioural activity as
      continuously measured by wrist actigraphy. Olopatadine, like d-chlorpheniramine,
      reduced the behavioural activity, while fexofenadine had no effect in any of the
      tests. No significant changes in the subjects' self-ratings of drowsiness were
      found with the three antihistamines. These results suggest that d
      chlorpheniramine and olopatadine, but not fexofenadine, produce sedative effects
      on psychomotor performance, and that the CNS profile of fexofenadine is different
      from that of olopatadine.

PMID- 14696021
TI  - Comparative cognitive and psychomotor effects of single doses of Valeriana
      officianalis and triazolam in healthy volunteers.
AB  - OBJECTIVES: To assess the cognitive and psychomotor effects of single oral doses
      of valerian in healthy volunteers in comparison with a placebo and the hypnotic
      agent triazolam. METHODS: In a double-blind, placebo-controlled, four-way
      crossover study nine healthy subjects (5 males, 4 females) received in random
      order valerian 500 mg, valerian 1000 mg, triazolam 0.25 mg and placebo. Doses
      were separated by a wash-out period of at least 1 week. Subjects were tested
      before each dose and at 2, 4 and 8 h after the dose of each compound using the
      critical flicker fusion (CFF), choice reaction time (CRT), digit symbol
      substitution test (DSST), symbol search test (SST), digit span test (DST) and
      visual analogue scales of mood. RESULTS: Repeated measures ANOVA was used to
      examine the changes in performance on tests over time and significant effects
      were further analysed using simple main effects analysis with least significant
      difference corrections. Statistically significant differences were only noted for
      the cognitive tests: SST (F(3, 8)=3.182, p<0.05) and DSST (F(3, 8)=9.688,
      p<0.005). In both cases the differences between groups were due to the effects of
      triazolam. CONCLUSION: These data confirm that at recommended therapeutic doses,
      triazolam has detrimental effects on cognitive processes in healthy volunteers as
      found in previous studies. Valerian was without effect on either cognitive or
      psychomotor performance in healthy volunteers at the doses used in this study.
      Should the hypnotic activity of valerian be confirmed in randomized double-blind
      trials it may be a less troublesome alternative to benzodiazepines in the
      treatment of insomnia.

PMID- 14696022
TI  - Risperidone use in Korean patients with Alzheimer's disease: optimal dosage and
      effect on behavioural and psychological symptoms, cognitive function and
      activities of daily living.
AB  - BACKGROUND: This study aimed to investigate the effect of risperidone on the
      behavioural and psychological symptoms (BPS), cognitive function and activities
      of daily living (ADL) of Alzheimer's disease (AD). The optimal dose of
      risperidone in Korean patients with AD was determined with respect to both
      efficacy and safety profiles. METHODS: This was an 8 week prospective, open
      labelled study with risperidone. The following efficacy measures were
      implemented: Behaviour Pathology in Alzheimer's Disease Rating Scale, Korean
      version for BPS; Korean version of mini-mental state examination for cognitive
      function; Barthel activities of daily living and blessed dementia rating scale
      for ADL; and global deterioration scale for global assessment of severity.
      Adverse events were recorded using the UKU side effect rating scale. RESULTS:
      Forty-eight patients completed the study. Risperidone was effective in reducing
      the BPS without affecting the cognitive and ADL domains of AD symptomatology.
      Risperidone dosages of 0.25 or 0.5 mg/day were most frequently administered and
      demonstrated the most favourable outcomes by efficacy and safety measures.
      Risperidone treatment was generally well tolerated, although extrapyramidal
      symptoms were noted in a dose-dependent manner. CONCLUSIONS: These results
      suggest that low dosages of risperidone are effective and favourable in reduction
      of the BPS for Korean patients with AD.

PMID- 14696023
TI  - Reduced short-term obsessive-compulsive symptoms in schizophrenic patients
      treated with risperidone: a single-blind prospective study.
AB  - BACKGROUND: Risperidone is a widely used agent as first-line treatment in
      schizophrenia with a favorable side-effect profile. However, a number of case
      reports have suggested an increase in obsessive-compulsive symptoms in patients
      treated with risperidone. OBJECTIVE: The aim of this study was to investigate the
      effect of risperidone on obsessive-compulsive symptoms in the treatment of
      schizophrenia. METHOD: Forty patients with DSM-IV diagnosis of schizophrenia were
      included in the study. The Yale-Brown obsessive compulsive scale was administered
      before, at the end of first and second months of treatment. Paired-samples t-test
      was used to compare the three assessments. RESULTS: There was not an increase,
      but a significant decrease, in YBOCS scores over time during risperidone
      treatment (p<0.05). CONCLUSION: In the present study risperidone caused a
      significant decrease in obsessive-compulsive symptoms in the treatment of
      schizophrenia.

PMID- 14696024
TI  - EEG abnormalities associated with antipsychotics: a comparison of quetiapine,
      olanzapine, haloperidol and healthy subjects.
AB  - In this study the effects of the atypical antipsychotics quetiapine and
      olanzapine, and the typical antipsychotic haloperidol on EEG patterns were
      retrospectively investigated in 81 patients under stable monotherapy with either
      drug (quetiapine: n=22, olanzapine: n=37, haloperidol: n=22). These three
      subgroups were compared with a control group of healthy subjects (n=30) which
      were matched regarding sex and age. Diagnoses of patients were schizophrenia (DSM
      IV 295.xx, n=61), brief psychotic disorder (DSM-IV 298.8, n=9), schizoaffective
      disorder (DSM-IV 295.70, n=8) and delusional disorder (DSM-IV 297.1, n=3). There
      were no statistically significant differences regarding demographic
      characteristics between the groups. Digital EEG recordings were retrieved from a
      database and visually assessed by two independent investigators, and one blinded
      regarding medication. One patient from the quetiapine group (5%), 13 olanzapine
      patients (35%), five of the haloperidol patients (23%) and two subjects of the
      control group (7%) had an abnormal EEG. Epileptiform activity was observed in
      four patients (11%) of the olanzapine group, and none in the others. EEG
      abnormalities were statistically significantly increased with dose in the
      olanzapine group, in contrast to patients treated with haloperidol, quetiapine or
      healthy subjects. In conclusion, EEG abnormalities seem to occur rarely in
      patients treated with quetiapine comparable to the control group, but
      significantly more often with haloperidol and olanzapine, possibly due to
      different receptor profiles of these substances. To our knowledge, this is the
      first electrophysiological investigation comparing the new atypical
      antipsychotics quetiapine, haloperidol, olanzapine with healthy subjects.

PMID- 14696026
TI  - An introduction to the special issues on juvenile psychopathy and some
      reflections on the current debate. Juvenile psychopathy: the debate.

PMID- 14696025
TI  - Prolonged QTc intervals in medicated patients with schizophrenia.
AB  - Psychotropic drugs have been associated with sudden deaths and the lengthening of
      corrected-QT interval (QTc) on the electrocardiogram which may be a precursor of
      life-threatening arrhythmias as reported with some of these drugs. The objectives
      of this study were to measure the frequency of QTc lengthening in patients with
      schizophrenia receiving psychotropic drugs, and to assess whether QTc lengthening
      was associated with certain psychotropic drugs and other risk factors. One
      hundred and sixty three patients with schizophrenia (104 males and 59 females)
      were included in the study. Clinical and demographic data were collected from the
      case records. One hundred healthy volunteers were recruited to establish values
      for upper limits of normal for measurement of QTc interval and dispersion. Eleven
      (6.7%) of the patients had a prolonged QTc interval. The significant predictors
      obtained from a logistic regression modelling were chlorpromazine, flupenthixol
      decanoate and fluphenazine decanoate. Caution should be exercised and monitoring
      with ECG should be considered in patients prescribed chlorpromazine and depot
      antipsychotic medications even at recommended doses.

PMID- 14696027
TI  - Subtypes of adolescent offenders: affective traits and antisocial behavior
      patterns.
AB  - Etiological models of life-course persistent offending often emphasize behavioral
      explanations. Suggestions that persistent offenders have psychopathy ignore the
      distinct non-behavioral features of the psychopathy disorder. Using a three
      factor model of the PCL-YV and cluster analysis with 259 incarcerated
      adolescents, we identified four distinct juvenile subtypes on the basis of
      affective, interpersonal, and behavioral dimensions. Prospective and
      retrospective comparisons of antisocial behavior patterns found the cluster
      comprising all three psychopathy dimensions to be the most chronic and severe.
      Impulsive features alone were strongly associated with severe antisocial
      behaviors retrospectively, but not prospectively. Findings rebut the proposal
      that disruptive behavioral and impulsive symptoms can identify "fledgling
      psychopaths." Assessments that disregard callous-unemotional traits will likely
      result in high false positive rates among serious adolescent offenders.
      Implications for developmental models of chronic offending are discussed in light
      of the need for further follow-up into adulthood.

PMID- 14696028
TI  - The 4 year stability of psychopathic traits in non-referred youth.
AB  - One significant limitation in research extending the construct of psychopathy to
      youth has been the absence of longitudinal studies testing the stability of
      psychopathic traits prior to adulthood. To begin to address this limitation, the
      current study estimated the stability of psychopathic traits over a 4 year period
      in a sample of non-referred children in the third, fourth, sixth, and seventh
      grades at the first assessment. For parent ratings of psychopathic traits,
      stability estimates using intra-class correlation coefficients ranged from 0.80
      to 0.88 across 2-4 years, with a stability estimate of 0.93 across all four
      assessments. There were also distinct trends in the patterns of stability found
      in the sample. Specifically, children rated as being initially high on these
      traits were more likely to be rated lower at later assessments than was the case
      for children rated initially low on these traits. Finally, the child's level of
      conduct problems, the socioeconomic status of the child's family, and the quality
      of parenting the child received were the most consistent predictors of stability
      of psychopathic traits.

PMID- 14696029
TI  - Views of the downward extension: comparing the Youth Version of the Psychopathy
      Checklist with the Youth Psychopathic traits Inventory.
AB  - Increasing interest in "juvenile psychopathy" has been met with scholarly debate
      about the validity of directly extending the adult construct of psychopathic
      personality disorder to youth. To inform this debate, this study of 160 serious
      adolescent offenders compared two alternative, adult-based conceptualizations of
      juvenile psychopathy: that of the Psychopathy Checklist: Youth Version (PCL:YV)
      and the self-report Youth Psychopathic traits Inventory (YPI). The results
      indicate that these two conceptualizations overlap only partially, with the YPI
      focusing more tightly on core interpersonal and affective features than the
      PCL:YV. Each conceptualization is reliable and predicts different forms of short
      term institutional misbehavior. However, only the YPI possesses a theoretically
      coherent, inverse association with anxiety. Despite this promise, these
      conceptualizations of psychopathy are less strongly associated with one another
      than they are with psychosocial markers of developmental maturity. This raises
      questions about their divergent validity and ability to identify a disorder that
      will remain stable during the transition from adolescence into adulthood.
      Implications for future longitudinal research on the validity, manifestations,
      and course of juvenile psychopathy are discussed.

PMID- 14696030
TI  - The validity of the Antisocial Process Screening Device as a self-report measure
      of psychopathy in adolescent offenders.
AB  - There is a growing interest in the assessment of adolescent psychopathy to enable
      early treatment and intervention. Recently, a self-report measure has been
      developed to assess psychopathic traits in adolescents. The Antisocial Process
      Screening Device (APSD), a self-report measure of psychopathic traits, and the
      Psychopathy Checklist: Youth Version (PCL:YV), a clinical rating scale, were
      administered to a sample of 100 incarcerated male adolescent offenders to assess
      the concurrent validity of the APSD. Results indicated that the APSD had limited
      concurrent validity with respect to the PCL:YV and that there appears to be a
      method effect in the measurement of psychopathy. Thus, it appears the APSD did
      not assess psychopathy in a manner parallel to that of the PCL:YV.

PMID- 14696031
TI  - Psychopathic features in a juvenile diversion population: reliability and
      predictive validity of two self-report measures.
AB  - The reliability and predictive validity of two experimental self-report versions
      of two measures of psychopathic features in youth, the Antisocial Process
      Screening Device (APSD: Frick & Hare, 2001) and a modified version of the Child
      Psychopathy Scale (CPS: Lynam, 1997) were examined in a sample of 69 arrested
      youth (M age = 14.4 years) referred to a juvenile diversion program. Parents or
      legal guardians completed parent-rating versions of the same measures.
      Reliability indicators for the APSD total measure were satisfactory although
      internal consistency indices (coefficient alpha) for the Callous/Unemotional and
      Impulsive/Conduct Problems scales were slightly lower than desirable. Reliability
      indicators for the CPS were excellent after deleting items that had poor
      corrected item-to-CPS total score correlations. Positive and statistically
      significant correlations for all measures were obtained with prospective measures
      of program failure (range 0.22-0.36) and rearrest at 1 year follow-up (range 0.33
      0.56). Although further research is needed prior to the clinical use of these
      measures, these results signal the potential of such measures to inform clinical
      judgments regarding treatment compliance and risk with justice-involved youth.

PMID- 14696032
TI  - Psychopathic traits predict attitudes toward a juvenile capital murderer.
AB  - The current study manipulated the presence/:absence of psychopathic traits and
      the ethnicity (Black/:White) of a juvenile capital murderer to examine their
      impact on layperson attitudes regarding what types of legal sanction were
      appropriate. Participants (N=360) reviewed a newspaper article concerning a death
      row inmate who was appealing his sentence primarily based on the fact that he
      committed the crime when he was 16 years of age. Compared to those in the control
      condition, those who read a scenario in which the defendant had been described at
      trial as exhibiting psychopathic traits (e.g. remorselessness, pathological
      lying) were significantly more likely to support a death sentence and less likely
      to believe he should receive any treatment in prison. Moreover, participant
      ratings of the extent to which they believed the defendant exhibited
      prototypically psychopathic traits (regardless of whether they were in the
      psychopathy or control condition) also significantly predicted these criterion
      measures. Ethnic status was relatively less influential, although participants
      were somewhat more punitive towards a Black defendant than a White defendant when
      considering the relevance of possible mitigating factors (e.g. history of sexual
      abuse).

PMID- 14696033
TI  - Prototypical analysis of adolescent psychopathy: investigating the juvenile
      justice perspective.
AB  - The past ten years have seen a dramatic increase in the empirical investigation
      of psychopathic characteristics in children and adolescents. In general, the
      focus of this research has been on the validation of assessment instruments to
      evaluate psychopathy as well as concurrent and predictive validity. Little
      attention has been directed toward elucidating the core characteristics of this
      construct. The current study expands on previous research by asking juvenile
      justice personnel (424 juvenile detention and probation officers) to identify the
      core characteristics of the construct via prototypical analysis for both male and
      female adolescents. Results of separate factor analyses by gender revealed five
      identifiable dimensions: juvenile delinquency, serious/violent conduct problems,
      narcissistic/manipulation of others, impulsivity/acting out, and family problems.
      The results suggest that juvenile justice personnel focus on a wide range of
      behavioral indicators as indicative of adolescent psychopathy in addition to
      affective and interpersonal characteristics typically viewed as crucial to the
      construct by clinicians.

PMID- 14696034
TI  - What can Drosophila tell us about serpins, thrombosis and dementia?
AB  - The validity of the fruit-fly as a model of human disease has been confirmed in a
      striking way by Green and colleagues.1 They show that the mutations causing a
      necrotic disease phenotype in Drosophila, precisely mirror those resulting in a
      group of well-studied but perplexing diseases in the human. These diseases,
      ranging from thrombosis to dementia, arise from mutations causing a
      conformational instability of serpin protease inhibitors. The findings provide
      clues as to the unusual severity and variable onset of such conformational
      diseases and demonstrate the potential of Drosophila as a model for their future
      study.

PMID- 14696035
TI  - Got milk? A pheromonal message for newborn rabbits.
AB  - A substance in rabbit milk, 2-methylbut-2-enal (2MB2), has been identified as a
      pheromone that triggers stereotypical searching behavior from rabbit pups. Pups
      respond to the odor of 2MB2 solutions in concentration-dependent manner, but fail
      to respond to 20 other volatile components in rabbit milk and 20 additional
      odorants. The effectiveness of 2MB2 generalizes across strains and breeds of
      rabbits, but is ineffective in closely related species. Finally, pup
      responsiveness to 2MB2 is innate and does not require learning. This study, for
      the first time, identifies a mammary pheromone that provides sufficient sensory
      cue for nipple attachment by newborns. In addition to contributing to our
      understanding of pheromonal communication, it provides an advantageous model
      system for neurobiologists.

PMID- 14696036
TI  - Mating-type locus homozygosis, phenotypic switching and mating: a unique sequence
      of dependencies in Candida albicans.
AB  - A small proportion of clinical strains of Candida albicans undergo white-opaque
      switching. Until recently it was not clear why, since most strains carry the
      genes differentially expressed in the unique opaque phase. The answer to this
      enigma lies in the mating process. The majority of C. albicans strains are
      heterozygous for the mating type locus MTL (a/alpha) and cannot undergo white
      opaque switching. However, when these cells undergo homozygosis at the mating
      type locus (i.e., become a/a or alpha/alpha), they can switch, and they must
      switch in order to mate. Even though the newly identified stages of mating mimic
      those of Saccharomyces cerevisiae, the process differs in its dependency on
      switching, and the effects switching has on gene regulation. This unique feature
      of C. albicans mating appears to be intimately intertwined with its pathogenesis.
      The unique, newly discovered dependencies of switching on homozygosis at the MTL
      locus and of mating on switching are, therefore, reviewed within the context of
      pathogenesis.

PMID- 14696037
TI  - The pleiotropic actions of vitamin D.
AB  - General knowledge of the role of vitamin D3 in human physiology has been shaped
      by its discovery as a preventive agent of nutritional rickets, a defect in bone
      development due to inadequate uptake of dietary calcium. Studies on the function
      of the hormonal form of vitamin D3, 1alpha,25-dihydroxyvitamin D3, have been
      greatly accelerated by the molecular cloning and structural analysis of the
      vitamin D3 receptor, which is a ligand-activated regulator of gene transcription.
      Molecular genetic techniques including genomics have helped reveal that 1alpha,25
      dihydroxyvitamin D3 can control more than calcium homeostasis. It has widespread
      effects on cellular differentiation and proliferation, and can modulate immune
      responsiveness, and central nervous system function. Moreover, accumulating
      epidemiological and molecular evidence suggests that 1alpha,25-dihydroxyvitamin
      D3 acts as a chemopreventive agent against several malignancies including cancers
      of the prostate and colon. Here, we survey the most-recent findings and discuss
      their implications for the potential therapeutic uses of vitamin D analogues.

PMID- 14696038
TI  - Reassessing the molecular biology of sperm-egg recognition with mouse genetics.
AB  - The zona pellucida is an extracellular coat that surrounds mammalian eggs and
      early embryos. This insoluble matrix separates germ from somatic cells during
      folliculogenesis and plays critical roles during fertilization and early
      development. The mouse and human zona pellucida contain three glycoproteins (ZP1
      or ZPB, ZP2, ZP3), the primary structures of which have been deduced by molecular
      cloning. Targeted mutagenesis of endogenous mouse genes and transgenesis with
      human homologues provide models to investigate the roles of individual zona
      components. Collectively, the genetic data indicate that no single mouse zona
      pellucida protein is obligatory for taxon-specific sperm binding and that two
      human proteins are not sufficient to support human sperm binding. An observed
      post-fertilization persistence of mouse sperm binding to "humanized" zona
      pellucida correlates with uncleaved ZP2. These observations are consistent with a
      model for sperm binding in which the supramolecular structure of the zona
      pellucida necessary for sperm binding is modulated by the cleavage status of ZP2.

PMID- 14696039
TI  - Functional genomics of the nicotinic acetylcholine receptor gene family of the
      nematode, Caenorhabditis elegans.
AB  - Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that
      bring about a diversity of fast synaptic actions. Analysis of the Caenorhabditis
      elegans genome has revealed one of the most-extensive and diverse nAChR gene
      families known, consisting of at least 27 subunits. Striking variation with
      possible functional implications has been observed in normally conserved motifs
      at the acetylcholine-binding site and in the channel-lining region. Some nAChR
      subunits are particular to neurons whilst others are present in both neurons and
      muscles. The localization of subunits in non-synaptic regions suggests novel
      roles for nAChRs. Genetic and heterologous expression studies have identified a
      subset of nAChR subunits that are important drug targets while the study of
      mutants has identified genes functionally-linked to nAChRs. Future studies using
      C. elegans offer the prospect of increasing our understanding of the functional
      diversity of a complex nAChR gene family as well as addressing the role of nAChRs
      and associated proteins in human disorders.

PMID- 14696040
TI  - Photosynthetic eukaryotes unite: endosymbiosis connects the dots.
AB  - The photosynthetic organelle of algae and plants (the plastid) traces its origin
      to a primary endosymbiotic event in which a previously non-photosynthetic protist
      engulfed and enslaved a cyanobacterium. This eukaryote then gave rise to the red,
      green and glaucophyte algae. However, many algal lineages, such as the
      chlorophyll c-containing chromists, have a more complicated evolutionary history
      involving a secondary endosymbiotic event, in which a protist engulfed an
      existing eukaryotic alga (in this case, a red alga). Chromists such as diatoms
      and kelps then rose to great importance in aquatic habitats. Another algal group,
      the dinoflagellates, has undergone tertiary (engulfment of a secondary plastid)
      and even quaternary endosymbioses. In this review, we examine algal diversity and
      show endosymbiosis to be a major force in algal evolution. This area of research
      has advanced rapidly and long-standing issues such as the chromalveolate
      hypothesis and the extent of endosymbiotic gene transfer have recently been
      clarified.

PMID- 14696041
TI  - LAT: a T lymphocyte adapter protein that couples the antigen receptor to
      downstream signaling pathways.
AB  - Adapter molecules in a variety of signal transduction systems link receptors to a
      limited number of commonly used downstream signaling pathways. During T-cell
      development and mature T-cell effector function, a multichain receptor (the pre-T
      cell antigen receptor or the T-cell antigen receptor) activates several protein
      tyrosine kinases. Receptor and kinase activation is linked to distal signaling
      pathways (PLC-gamma1 activation, Ca2+ influx, PKC activation and Ras/Erk
      activation) via the adapter protein LAT (Linker for Activation of T cells).
      Structure/function studies of LAT including expression of selected LAT point
      mutations in vivo reveals that these multiple pathways are integrated at the
      level of the LAT adapter. These studies suggest that similar levels of control
      may be found in other systems where adapter molecules are known to have important
      functions.

PMID- 14696042
TI  - The next step in systems biology: simulating the temporospatial dynamics of
      molecular network.
AB  - As a result of the time- and context-dependency of gene expression, gene
      regulatory and signaling pathways undergo dynamic changes during development.
      Creating a model of the dynamics of molecular interaction networks offers
      enormous potential for understanding how a genome orchestrates the developmental
      processes of an organism. The dynamic nature of pathway topology calls for new
      modeling strategies that can capture transient molecular links at the runtime.
      The aim of this paper is to present a brief and informative, but not all
      inclusive, viewpoint on the computational aspects of modeling and simulation of a
      non-static molecular network.

PMID- 14696043
TI  - Cross-strand disulphides in cell entry proteins: poised to act.
AB  - Cross-strand disulphides (CSDs) are unusual bonds that link adjacent strands in
      the same beta-sheet. Their peculiarity relates to the high potential energy
      stored in these bonds, both as torsional energy in the highly strained disulphide
      linkage and as deformation energy stored in the sheet itself. CSDs are relatively
      rare in protein structures but are conspicuous by their presence in proteins that
      are involved in cell entry. The finding that entry of botulinum neurotoxin and
      HIV into mammalian cells involves cleavage of CSDs suggests that the activity of
      other cell entry proteins may likewise involve cleavage of these bonds. We
      examine emerging evidence of the involvement of these unusual disulphides in cell
      entry events.

PMID- 14696044
TI  - Neuroprotection by monoamine oxidase B inhibitors: a therapeutic strategy for
      Parkinson's disease?
AB  - Parkinsonism (PD) is a neurodegenerative disorder of the brain resulting in
      dopamine deficiency caused by the progressive death of dopaminergic neurons. PD
      is characterized by a combination of rigidity, poverty of movement, tremor and
      postural instability. Selegiline is a selective and irreversible propargylamine
      type B monoamine oxidase (MAO-B) inhibitor. This drug, which inhibits dopamine
      metabolism, has been effectively used in the treatment of PD. However, its
      therapeutic effects are compromised by its many neurotoxic metabolites. To
      circumvent this obstacle, a novel MAO-B inhibitor, rasagiline, was developed.
      Paradoxically, the neuroprotective mechanism of propargylamines in different
      neuronal models appears to be independent of MAO-B inhibition. Recent
      investigations into the neuroprotective mechanism of propargylamines indicate
      that glyceraldehyde-3-phosphate dehydrogenase (GAPDH), MAO-B and/or other unknown
      proteins may represent pivotal proteins in the survival of the injured neurons.
      Delineation of the mechanism(s) involved in the neuroprotective effects exerted
      by MAO-B inhibitors may provide the key to preventive novel therapeutic
      modalities.

PMID- 14696045
TI  - The role of insulin as an antithrombotic humoral factor.
AB  - Insulin is well known for its essential role in carbohydrate metabolism: insulin
      deficiency results in the development of diabetes mellitus. It has been known for
      many years that people with diabetes mellitus are predisposed to develop
      thrombotic diseases including myocardial infarction. It was thought that the
      thrombus formation was the consequence of impaired carbohydrate metabolism. In
      recent years, it has become apparent that insulin is capable of ameliorating
      several pathophysiological events, leading to the inhibition and dissolution of
      the formed thrombus in the system. These insulin-induced events include
      inhibition of platelet aggregation by prompting the synthesis of NO in platelet
      and prostacyclin in endothelial cells. Furthermore, insulin upregulates
      prostacyclin receptors and downregulates alpha(2) adrenergic receptor in
      platelets, thereby amplifying the inhibition of platelet aggregation. Insulin
      also releases tissue plasminogen activator, a potent thrombolytic enzyme, from
      the platelet membrane which dissolves the formed thrombus leading to the
      resumption of normal blood circulation. In effect, insulin could be an essential
      tool in the control of thrombotic disorders.

PMID- 14696046
TI  - Here is the evidence, now what is the hypothesis? The complementary roles of
      inductive and hypothesis-driven science in the post-genomic era.
AB  - It is considered in some quarters that hypothesis-driven methods are the only
      valuable, reliable or significant means of scientific advance. Data-driven or
      'inductive' advances in scientific knowledge are then seen as marginal,
      irrelevant, insecure or wrong-headed, while the development of technology--which
      is not of itself 'hypothesis-led' (beyond the recognition that such tools might
      be of value)--must be seen as equally irrelevant to the hypothetico-deductive
      scientific agenda. We argue here that data- and technology-driven programmes are
      not alternatives to hypothesis-led studies in scientific knowledge discovery but
      are complementary and iterative partners with them. Many fields are data-rich but
      hypothesis-poor. Here, computational methods of data analysis, which may be
      automated, provide the means of generating novel hypotheses, especially in the
      post-genomic era.

PMID- 14696047
TI  - Millimeter wave exposure reverses TPA suppression of gap junction intercellular
      communication in HaCaT human keratinocytes.
AB  - The effect of 30.16 GHz millimeter wave (MMW) exposure at 1.0 and 3.5 mW/cm2 on
      gap junction intercellular communication (GJIC) was studied in cultured HaCaT
      keratinocytes, using the fluorescence recovery after photobleaching (FRAP)
      technique and laser confocal scanning microscopy to follow the intracellular
      movement of 5,6-carboxyfluorescein diacetate dye. While MMW exposure alone for 1
      h at either 1.0 or 3.5 mW/cm2 did not affect GJIC, MMW exposure in combination
      with 5 ng/ml TPA treatment reversed TPA induced suppression of GJIC. Exposure at
      1.0 mW/cm2 resulted in a partial reversal, and exposure at 3.5 mW/cm2 resulted in
      essentially full reversal of the TPA suppression.

PMID- 14696048
TI  - Electromagnetic field exposure and health among RF plastic sealer operators.
AB  - Operators of RF plastic sealers (RF operators) are an occupational category
      highly exposed to radiofrequency electromagnetic fields. The aim of the present
      study was to make an appropriate exposure assessment of RF welding and examine
      the health status of the operators. In total, 35 RF operators and 37 controls
      were included. The leakage fields (electric and magnetic field strength) were
      measured, as well as induced and contact current. Information about welding time
      and productivity was used to calculate time integrated exposure. A
      neurophysiological examination and 24 h ECG were also carried out. The
      participants also had to answer a questionnaire about subjective symptoms. The
      measurements showed that RF operators were exposed to rather intense electric and
      magnetic fields. The mean values of the calculated 6 min, spatially averaged E
      and H field strengths, in line with ICNIRP reference levels, are 107 V/m and 0.24
      A/m, respectively. The maximum measured field strengths were 2 kV/m and 1.5 A/m,
      respectively. The induced current in ankles and wrists varied, depending on the
      work situation, with a mean value of 101 mA and a maximum measured value of 1 A.
      In total, 11 out of 46 measured RF plastic sealers exceeded the ICNIRP reference
      levels. RF operators, especially the ready made clothing workers had a slightly
      disturbed two-point discrimination ability compared to a control group. A
      nonsignificant difference between RF operators and controls was found in the
      prevalence of subjective symptoms, but the time integrated exposure parameters
      seem to be of importance to the prevalence of some subjective symptoms: fatigue,
      headaches, and warmth sensations in the hands. Further, RF operators had a
      significantly lower heart rate (24 h registration) and more episodes of
      bradycardia compared to controls.

PMID- 14696049
TI  - Dosimetric analysis of the carousel setup for the exposure of rats at 1.62 GHz.
AB  - The so-called carousel setup has been widely utilized for testing the hypotheses
      of adverse health effects on the central nervous system (CNS) due to mobile phone
      exposures in the frequency bands 800-900 MHz. The objectives of this article were
      to analyze the suitability of the setup for the upper mobile frequency range,
      i.e., 1.4-2 GHz, and to conduct a detailed experimental and numerical dosimetry
      for the setup at the IRIDIUM frequency band of 1.62 GHz. The setup consists of a
      plastic base on which ten rats, restrained in radially positioned tubes, are
      exposed to the electromagnetic field emanating from a sleeved dipole antenna at
      the center. Latest generation miniaturized dosimetric E field and temperature
      probes were used to measure the specific absorption rate (SAR) inside the brain
      of three rat cadavers of the Lewis strain and two rat cadavers of the Fisher 344
      strain. A numerical analysis was conducted on the basis of three numerical rat
      phantoms with voxel sizes between 1.5 and 0.125 mm3 that are based on high
      resolution MRI scans of a 300 g male Wistar rat and a 370 g male Sprague-Dawley
      rat. The average of the assessed SAR values in the brain was 2.8 mW/g per W
      antenna input power for adult rats with masses between 220 and 350 g and 5.3 mW/g
      per W antenna input power for a juvenile rat with a mass of 95 g. The strong
      increase of the SAR in the brain with decreasing animal size was verified by
      simulations of the absorption in numerical phantoms scaled to sizes between 100
      and 500 g with three different scaling methods. The study also demonstrated that
      current rat phantom models do not provide sufficient spatial resolution to
      perform absolute SAR assessment for the brain tissue. The variation of the
      SAR(brain)(av) due to changes in position was assessed to be in the range from
      +15% to -30%. A study on the dependence of the performance of the carousel setup
      on the frequency revealed that efficiency, defined as SAR(brain)(av) per W
      antenna input power, and the ratio between SAR(brain)(av) and SAR(body)(av) are
      optimal in the mobile communications frequency range, i.e., 0.8-3 GHz.

PMID- 14696050
TI  - A single magnetic field exposure system for sequential investigation of real time
      and downstream cellular responses.
AB  - To be able to correlate real time membrane potential or ion flux changes with
      further downstream gene transcription responses due to extremely low frequency
      (ELF) electromagnetic field (EMF) exposure, we devised an experimental system
      consisting of a pair of symmetric circular coils. This system can be used on an
      inverted microscope stage (real time signaling) as well as inside controlled
      environment incubators (gene transcription end points). The system includes a
      unique, custom made switch box for blinding the experimental staff and a power
      amplifier. We report herein the design and characterization of the system with
      respect to parameters considered important in in vitro ELF-EMF exposure studies,
      including linear magnetic field distribution, compensation for microscope
      objective lens interference, heating effects of the coils, and harmonic content
      of the signals.

PMID- 14696051
TI  - Effects of electromagnetic field emitted by cellular phones on the EEG during an
      auditory memory task: a double blind replication study.
AB  - The effects of electromagnetic fields (EMF) emitted by cellular phones on the
      event related desynchronization/synchronization (ERD/ERS) of the 4-6, 6-8, 8-10,
      and 10-12 Hz electroencephalogram (EEG) frequency bands were studied in 24 normal
      subjects performing an auditory memory task. This study was a systematic
      replication of our previous work. In the present double blind study, all subjects
      performed the memory task both with and without exposure to a digital 902 MHz
      field in a counterbalanced order. We were not able to replicate the findings from
      our earlier study. All eight of the significant changes in our earlier study were
      not significant in the present double blind replication. Also, the effect of EMF
      on the number of incorrect answers in the memory task was inconsistent. We
      previously reported no significant effect of EMF exposure on the number of
      incorrect answers in the memory task, but a significant increase in errors was
      observed in the present study. We conclude that EMF effects on the EEG and on the
      performance on memory tasks may be variable and not easily replicable for unknown
      reasons.

PMID- 14696052
TI  - Absence of genotoxicity in human blood cells exposed to 50 Hz magnetic fields as
      assessed by comet assay, chromosome aberration, micronucleus, and sister
      chromatid exchange analyses.
AB  - In the past, epidemiological studies indicated a possible correlation between the
      exposure to ELF fields and cancer. Public concern over possible hazards
      associated with exposure to extremely low frequency magnetic fields (ELFMFs)
      stimulated an increased scientific research effort. More recent research and
      laboratory studies, however, have not been able to definitively confirm the
      correlation suggested by epidemiological studies. The aim of this study was to
      evaluate the effects of 50 Hz magnetic fields in human blood cells exposed in
      vitro, using several methodological approaches for the detection of genotoxicity.
      Whole blood samples obtained from five donors were exposed for 2 h to 50 Hz, 1 mT
      uniform magnetic field generated by a Helmholtz coil system. Comet assay, sister
      chromatid exchanges (SCE), chromosome aberrations (CA), and micronucleus (MN)
      tests were used to assess DNA damage, one hallmark of malignant cell
      transformation. The effects of a combined exposure with X-rays were also
      evaluated. Results obtained do not show any significant difference between ELFMFs
      exposed and unexposed samples. Moreover, no synergistic effect with ionizing
      radiation has been observed. A slight but significant decrease of cell
      proliferation was evident in ELFMFs treated samples and samples subjected to the
      combined exposure.

PMID- 14696053
TI  - Radial arm maze performance of rats following repeated low level microwave
      radiation exposure.
AB  - We examined the possibility of changes in "working" memory of rats following
      whole body exposure to microwave (MW) radiation. During each of 10 days, we
      exposed rats within circularly polarized waveguides for 45 min to 2450 MHz fields
      at whole body SARs of 0.6 W/kg (2 micros pulses, 500 pps), followed by testing in
      a 12 arm, radial arm maze (RAM). Rats received a preexposure injection of one of
      three psychoactive compounds or saline, to determine whether a compound would
      interact with MW exposure to affect performance in the maze. Error rate, i.e.,
      reentry into arms already visited, and time to criterion data for 10 consecutive
      days of testing were analyzed by a three way analysis of variance (ANOVA) using
      main effects of "exposure" and "drug" and a repeated factor of "test day." Our
      alpha limit for significance was P <.05. Analyzes of error rates revealed no
      significant exposure effect, no significant drug effect and no significant
      interaction between the two main factors. There was a significant difference in
      test days, as expected, with repeated test-trial days, which indicates that
      learning was accomplished. There was no significant interaction of test day and
      the other two factors. The results of our analyzes of time to criterion data
      included no significant exposure effect, a significant drug effect, a significant
      test day effect, and a significant interaction between drug and test day factors.
      Post hoc analyzes of the drug factor revealed that rats treated with either
      physostigmine or nalrexone hydrochloride, took significantly longer to complete
      the maze task than rats pretreated with saline or with naloxone methodide. We
      conclude that there is no evidence from the current study that exposure to of MW
      radiation under parameters examined caused decrements in the ability of rats to
      learn the spatial memory task.

PMID- 14696054
TI  - Exposure assessment of ELF magnetic fields in urban environments in Extremadura
      (Spain).
AB  - We present the results of a study of the extremely low frequency (ELF) magnetic
      fields in urban environments of the Extremadura region (Spain). The study
      included a spectral analysis, an analysis of the temporal variation, and spot
      measurements in the streets of four cities. The spectral analysis showed that the
      main source of magnetic field exposure was that corresponding to the principal
      power frequency (50 Hz) and its third harmonic. The magnetic flux density
      measured at one point over 24 h presented rapid fluctuations in short time
      periods. Smoothing the time series eliminated these fluctuations, showing a
      temporal evolution associated with the differing levels of power consumption over
      the course of the day. The values of the spot measurements taken in the streets
      were all below the ICNIRP reference level, although 30% surpassed 0.2 microT, the
      value that some epidemiological studies take as the threshold above which there
      exist risks of effects that could be harmful to health. The values found for the
      magnetic flux density in these urban settings were generally greater than values
      reported in the literature for residential areas, and similar to, although in
      some cases less than those in workplace environments.

PMID- 14696055
TI  - Lack of alterations on meiotic chromosomes and morphological characteristics of
      male germ cells in mice exposed to a 60 Hz and 2.0 mT magnetic field.
AB  - The effect of in vivo exposure of mice to a 60 Hz sinusoidal magnetic field (MF)
      at 2.0 mT on male germ cells was studied. The cytological endpoints measured
      included meiotic chromosome aberrations in spermatocytes and sperm morphology.
      Three independent experiments were carried out: (a) animals exposed for 72 h, (b)
      10 days/8 h daily, and (c) 72 h exposure to MF plus 5 mg/kg of Mitomycin-C. No
      statistically significant differences indicative of MF effects were observed
      between MF exposed and control animals. In addition, an opposite effect between
      MF exposure and Mitomycin-C treatment in terms of chromosomal aberrations and
      sperm morphology was observed.

PMID- 14696056
TI  - Comments on "Bioelectrical parameters of the whole human body obtained through
      bioelectrical impedance analysis".

PMID- 14696057
TI  - Formalization of the MESF unit of fluorescence intensity.
AB  - This report summarizes the work performed during the past two years at the
      National Institute of Standards and Technology (NIST) in the refinement and
      formal definition of the MESF unit of fluorescence intensity. In addition to the
      theory underlying the MESF unit, considerations of error analysis are also
      presented. The details of this work may be found in the three publications of the
      NIST Journal of Research (www.nist.gov) listed as the references 2-4. The use of
      the fluorescence intensity unit provides a tool to compare quantitative
      fluorescence intensity measurements over time and across platforms.

PMID- 14696058
TI  - Albumin enhanced morphometric image analysis in CLL.
AB  - BACKGROUND: The heterogeneity of lymphocytes from patients with chronic
      lymphocytic leukemia (CLL) and blood film artifacts make morphologic
      subclassification of this disease difficult. METHODS: We reviewed paired blood
      films prepared from ethylene-diamine-tetraacetic acid (ETDA) samples with and
      without bovine serum albumin (BSA) from 82 CLL patients. Group 1 adhered to NCCLS
      specifications for the preparations of EDTA blood films. Group 2 consisted of
      blood films containing EDTA and a 1:12 dilution of 22% BSA. Eight patients were
      selected for digital photomicroscopy and statistical analysis. Approximately 100
      lymphocytes from each slide were digitally captured. RESULTS: The mean cell area
      +/- standard error was 127.8 microm(2) +/- 1.42 for (n = 793) for group 1 versus
      100.7 microm(2) +/- 1.39 (n = 831) for group 2. The nuclear area was 88.9
      microm(2) +/- 0.85 for group 1 versus 76.4 microm(2) +/- 0.83 for group 2. For
      the nuclear transmittance, the values were 97.6 +/- 0.85 for group 1 and 104.1 +/
      0.83 for group 2. The nuclear:cytoplasmic ratios were 0.71 +/- 0.003 for group 1
      and 0.78 +/- 0.003 for group 2. All differences were statistically significant (P
      < 0.001). CONCLUSIONS: BSA addition results in the reduction of atypical
      lymphocytes and a decrease in smudge cells. BSA also decreases the lymphocyte
      area and nuclear area, whereas nuclear transmittance and nuclear:cytoplasmic
      ratio are increased. A standardized method of slide preparation would allow
      accurate interlaboratory comparison. The use of BSA may permit better
      implementation of the blood film-based subclassification of CLL and lead to a
      better correlation of morphology with cytogenetics and immunophenotyping.
      Published 2003 Wiley-Liss, Inc.

PMID- 14696059
TI  - Automatic quantification of gene amplification in clinical samples by IQ-FISH.
AB  - BACKGROUND: The reliable detection and quantification of gene amplifications is
      crucial to clinical practice. Although there are different detection techniques,
      the fluorescence in situ hybridization (FISH) method has become highly accepted
      over past years because it is a reliable, robust, and quick method.
      Unfortunately, automatic quantification of gene amplification based on
      fluorescence intensities has not been possible thus far. Because current spot
      counting methods are reliable only when analyzing low amplification rates, we
      attempted to establish another method, i.e., to quantify the intensity of
      different FISH signals using an automatic fluorescence microscopical device on
      interphase nuclei: interphase quantitative FISH (IQ-FISH). METHODS: We quantified
      the fluorescence intensities of the differently labeled FISH probes (MYCN and
      D2Z) hybridized to three different neuroblastoma cell lines, six peripheral blood
      (PB) samples, 10 spiked PB samples, and nine neuroblastoma samples using the
      Metafer4 system (MetaSystems, Altlussheim, Germany). To obtain the MYCN copy
      number per cell, the ratio between the fluorescence intensities of the MYCN gene
      and reference sequence (D2Z) was calculated. For automatic analysis of the HER
      2/neu status in tumor cells, labeled FISH probes specific for HER-2/neu and a
      chromosome 17-specific probe were hybridized to peripheral blood and tumor
      specimens and analyzed using the automatic device. RESULTS: When measuring the
      fluorescence intensity per cell for both probe pairs (MYCN/D2Z and HER-2/17p),
      amplified and non-amplified cells, showed distinct peaks with only little
      overlap. Whereas normal cells showed a fluorescence ratio peak for MYCN/D2Z
      between 200 and 800, cells with MYCN amplification clearly exceeded this ratio
      value (1000 to 25,000). When mixing a varying number of MYCN amplified cells
      (range 9-91%) to normal PB, the spiked tumor cells could be identified. Even one
      neuroblastoma tumor cell in 1000 mononucleated cells could reliably be detected
      using our device. In neuroblastoma patient samples, non-amplified cells were
      distinguished from amplified cells. Automatically and manually counted signals
      gave matching results in amplified and non-amplified samples. HER-2/neu-amplified
      cells were automatically detected in the breast cancer samples analyzed.
      CONCLUSION: The automatic measurement of fluorescence signal intensities not only
      allows a reliable discrimination between non-amplified and amplified cells but
      also exact quantification of amplified sequences. This is the prerequisite for
      the following applications: detection of amplified cells in the bone marrow and
      second-look specimens; comparison between primary and relapse or pre- and post
      chemotherapeutic specimens; detection of tumors with focal gene amplification;
      and quantification of elimination of amplified gene sequences.

PMID- 14696060
TI  - Flow cytometric quantitation of red blood cell vesicles in thalassemia.
AB  - BACKGROUND: Thalassemia is a hereditary hemolytic anemia caused by mutations in
      the globin gene complex. Circulatory disturbances including arterial and venous
      thrombosis have also been noted in these patients. Aggregability of abnormal RBC
      and the high level of membrane-derived microparticles stemming from activated
      platelets and other blood cells are thought to be responsible for the associated
      thrombotic risk. Destruction of RBC is also thought to be an important
      pathophysiological consequence, particularly through the formation of circulating
      vesicles. To our knowledge, there has been no attempt to quantitatively evaluate
      the number of RBC vesicles in thalassemia. This prompted us to study the level of
      RBC vesicles in the peripheral blood of thalassemia patients using quantitative
      flow cytometry. METHODS: Whole blood from each subject was doubly stained for RBC
      and platelet or annexin V markers, together with the known density TruCount
      beads. RBC vesicles were gated according to their forward/side scatter and RBC
      marker. Percentage of RBC vesicles and their absolute number were analyzed by
      flow cytometry. RESULTS: Our data indicated that RBC vesicles were annexin V
      positive. The number of annexin V-positive events was higher than their intact
      RBCs. RBC vesicles were present in both normal and thalassemic blood samples, but
      the numbers of RBC vesicles were significantly higher in thalassemia. Both the
      percentage and the absolute number of RBC vesicles were especially marked in
      splenectomized subjects with beta-thalassemia/Hemoglobin E. When clinical and
      hematological indices were compared with RBC vesicles, there was an inverse
      relationship between the degree of severity in thalassemia patients and the
      number of RBC vesicles. CONCLUSION: Flow cytometric quantitation of RBC vesicles
      is simple, reliable and may offer new insights in to study of the relationship
      between defective hemoglobin synthesis, RBC perturbation and pathophysiological
      complications in thalassemia.

PMID- 14696061
TI  - Monitoring hyperproliferative disorders in human skin: flow cytometry of changing
      cytokeratin expression.
AB  - BACKGROUND: Monitoring dynamics of different cell populations in solid tissues
      using flow cytometry has several limitations. The interaction and changes in
      epidermal subpopulations in hyperproliferative skin disorders such as psoriasis,
      a very common chronic inflammatory skin disease, may, however, elucidate the role
      of different cell populations in the pathogenesis and the effect of therapy in
      these disorders. We describe a new, simple method for identifying and quantifying
      different epidermal subpopulations in hyperproliferative skin disorders and an in
      vivo model for epidermal hyperproliferation by using six-parameter assessment and
      three-color flow cytometry. METHODS: Epidermal single-cell suspensions were
      derived from normal human skin before and after standardized injury and from
      untreated and treated psoriatic lesions. Samples were stained with anti
      cytokeratins 6 (K6) and 10 (K10), anti-vimentin, and 4',6-diamidino-2
      phenylindole. With three-color flow cytometry, different epidermal subpopulations
      were further defined by six different parameters. RESULTS: Correlations were
      found for mild psoriasis and K10(+)K6(-) cells and for moderate psoriasis and
      K10(-)K6(+) cells. Treatment of mild psoriasis resulted in a 70% increase of the
      K10(+)K6(-) cells and an 18% decrease of the K10(-)K6(-) cells, whereas treatment
      of more severe psoriasis resulted in a 77% increase of the K10(+)K6(-) cells and
      a 33% decrease of the K10(-)K6(+) cells. The tape-stripping model showed changes
      in suprabasal keratin expression before proliferative activity. CONCLUSIONS: The
      present flow cytometric assay permits simultaneous quantification of epidermal
      differentiation, inflammation, proliferation, and hyperproliferation-associated
      keratinization and provides information on pathogenesis and therapy of
      hyperproliferative skin disorders.

PMID- 14696062
TI  - Visual scoring versus histogram subtraction of in vivo binding of immunoglobulins
      against platelets after transfusion.
AB  - BACKGROUND: We developed a technique, in vivo binding of immunoglobulins in the
      platelet immunofluorescence test (IVBI-PIFT), that detects immunoglobulins bound
      in vivo to transfused platelets. The visually scored results of this technique,
      however, are susceptible to interobserver variation. We describe a more objective
      method to generate results in IVBI-PIFT. METHODS: We studied 201 samples in 120
      patients with hematologic malignancies in the IVBI-PIFT. Histogram subtraction,
      i.e., fluorescence (anti-immunoglobulin G and fluorescein isothiocyanate)
      histogram before platelet transfusion subtracted from the histogram after
      platelet transfusion, was compared with visual scoring (pattern 1: no enhanced
      fluorescence before and after transfusion; pattern 2: enhanced fluorescence
      before and after platelet transfusion; pattern 3: enhanced fluorescence before
      transfusion; pattern 4: enhanced fluorescence after transfusion, interpreted as
      alloimmunization). After histogram subtraction, the number of remaining events
      (events post substraction, EPS) and the mean amount of fluorescence of these
      remaining events (mean channel post substraction, MCPS) were used and compared
      with the visual scoring and with platelet survival after transfusion. RESULTS: In
      26 (13%) of the 201 samples studied in the IVBI-PIFT, fewer than three of five
      observers agreed on the visually scored pattern. In the 175 (87%) remaining
      samples, histogram subtraction showed a significant differentiation between
      pattern 4 and patterns 1 and 2 by using EPS, whereas patterns 4 and 3 were
      distinguished by using MCPS. The combination of EPS and MCPS differentiated best
      between pattern 4 and patterns 1, 2, and 3 (73% sensitivity, 96% specificity, 79%
      positive predictive value, and 95% negative predictive value). In contrast, the
      predictive value for platelet recovery after 1 and 16 h of pattern 4 from the
      visual scoring method and the results of histogram subtraction were poor.
      CONCLUSION: This objective method of histogram subtraction correlated well with
      the visual scoring method of IVBI-PIFT.

PMID- 14696063
TI  - Perfect count: a novel approach for the single platform enumeration of absolute
      CD4+ T-lymphocytes.
AB  - BACKGROUND: The derivation of reliable CD4(+) T lymphocyte counts is vital for
      the monitoring of disease progression and therapeutic effectiveness in HIV(+)
      individuals. Flow cytometry has emerged as the method of choice for CD4(+) T
      lymphocyte enumeration, with single-platform technology, coupled with reference
      counting beads, fast becoming the "gold standard." However, although single
      platform, bead-based, sample acquisition requires the ratio of beads to cells to
      remain unchanged, there is no available method, until recently, to monitor this.
      METHODS: Perfect Count beads have been developed to address this issue and to
      incorporate two bead populations, with different densities, to allow the
      detection of inadequate mixing. Comparison of the relative proportions of both
      beads with the manufacture's defined limits enables an internal QC check during
      sample acquisition. In this study, we have compared CD4(+) T lymphocyte counts,
      obtained from 104 HIV(+) patients, using TruCount beads with MultiSet software
      (defined as the predicated method) and the new Perfect Count beads, incorporating
      an in house sequential gating strategy. RESULTS: We have demonstrated an
      excellent degree of correlation between the predicate method and the Perfect
      Count system (r(2) = 0.9955; Bland Altman bias +27 CD4(+) T lymphocytes/microl).
      CONCLUSIONS: The Perfect Count system is a robust method for performing single
      platform absolute counts and has the added advantage of having internal QC
      checks. Such an approach enables the operator to identify potential problems
      during sample preparation, acquisition and analysis.

PMID- 14696064
TI  - Bovine serum albumin in the preparation of peripheral blood smears.

PMID- 14696067
TI  - Isomers of C20: an energy profile III.
AB  - Semiempirical calculations, at the PM3 level provided within the Winmopac v2.0
      software package, are used to geometrically optimize and determine the absolute
      energies (heats of formation) of a variety of C(20) isomers that are predicted to
      exist in and around the ring and cage isomers. Using the optimized Cartesian
      coordinates for the ring and the cage isomers, a saddle-point calculation was
      performed. The resulting energy profile, consisting of a series of peaks and
      valleys, is used as a starting point for the identification and location of
      fifteen additional isomers of C(20) that are predicted to be energetically
      stable, both via geometry optimizations and force constant analysis. These
      additional isomers were subsequently determined to lie adjacent to one another on
      the potential surface and establish a step-wise transformation between the ring
      and the cage. Transition-state optimization of the Cartesian coordinates at the
      saddle point between adjacent isomers was performed to quantify the energy of the
      transition state. The step-wise process from one isomer to another, which extends
      out over the three-dimensional surface, is predicted to require approximately 15%
      less energy than that of the direct, two-dimensional transformation predicted in
      the bowl-cage profile. However, the net atomic rearrangement for the step-wise
      process is about four times greater than that of the direct process. Although
      less in energy, the amount of atomic rearrangement in the step-wise process would
      make the occurrence of such a route prohibitive. Utilizing the direct distance
      separating the three primary isomers (ring, bowl, cage), the method of
      triangulation is performed to quantitatively position other C(20) structures on
      the potential surface, relative to the ring, bowl, and cage isomers.

PMID- 14696066
TI  - Class I ribonucleotide reductase revisited: the effect of removing a proton on
      Glu441.
AB  - The substrate mechanism of class I ribonucleotide reductase has been revisited
      using the hybrid density functional B3LYP method. The molecular model used is
      based on the X-ray structure and includes all the residues of the R1 subunit
      commonly considered in the RNR substrate conversion scheme: Cys439 initiating the
      reaction as a thiyl radical, the redox-active cysteines Cys225 and Cys462, and
      the catalytically important Glu441 and Asn437. In contrast to previous
      theoretical studies of the overall mechanism, Glu441 is added as an anion. All
      relevant transition states have been optimized, including one where an electron
      is transferred 8 A from the disulfide to the substrate simultaneously with a
      proton transfer from Glu441. The calculated barrier for this step is 19.1
      kcal/mol, which can be compared to the rate-limiting barrier indicated by
      experiments of about 17 kcal/mol. Even though the calculated barrier is somewhat
      higher than the experimental limit, the discrepancy is within the normal error
      bounds of B3LYP. The suggestion from the present modeling study is thus that a
      protonated Glu441 does not need to be present at the active site from the
      beginning of the catalytic cycle. However, the previously suggested mechanism
      with an initial protonation of Glu441 cannot be ruled out, because even with the
      cost added for protonation of Glu441 with a typical pK(a) of 4, the barrier for
      that mechanism is lower than the one obtained for the present mechanism. The
      results are compared to experimental results and suggestions.

PMID- 14696068
TI  - Krylov subspace accelerated inexact Newton method for linear and nonlinear
      equations.
AB  - A Krylov subspace accelerated inexact Newton (KAIN) method for solving linear and
      nonlinear equations is described, and its relationship to the popular direct
      inversion in the iterative subspace method [DIIS; Pulay, P., Chem Phys Lett 1980,
      393, 73] is analyzed. The two methods are compared with application to simple
      test equations and the location of the minimum energy crossing point of potential
      energy surfaces. KAIN is no more complicated to implement than DIIS, but can
      accommodate a wider variety of preconditioning and performs substantially better
      with poor preconditioning. With perfect preconditioning, KAIN is shown to be very
      similar to DIIS. For these reasons, KAIN is recommended as a replacement for
      DIIS.

PMID- 14696069
TI  - Time-reversible always stable predictor-corrector method for molecular dynamics
      of polarizable molecules.
AB  - An improved method for classic molecular dynamics of polarizable molecules is
      proposed. The method uses a predictor, one evaluation of the electrostatic field
      per integration step, and relaxation (damping). The self-consistent solution is
      approximated with error of the second order (with respect to the timestep). The
      time reversibility (long-time energy conservation) error is of the (2n - 1)th
      order, where n is the predictor length. The method is easy to implement,
      efficient, accurate, and suitable for any model of polarizability.

PMID- 14696070
TI  - A simple computational scheme for obtaining localized bonding schemes and their
      weights from a CASSCF wave function.
AB  - We devise and apply a simple computational scheme for obtaining localized bonding
      schemes and their weights from a CASSCF wave function. These bonding schemes are
      close to resonance structures drawn by chemists. Firstly, a CASSCF wave function
      is computed. Secondly, the CASSCF computation is repeated but now the delocalized
      complete active space MOs are substituted by Weinhold's localized natural atomic
      orbitals. In this way the original CASSCF wave function is represented by a
      sequence of Slater determinants composed of localized natural atomic orbitals.
      Thus, a standard CASSCF wave function can be reinterpreted in terms of a local
      picture. To test the method we obtain localized bonding schemes and their weights
      for the ground and the pi-pi* excited state of ethylene. Moreover, bonding
      schemes and their weights are derived for the ground, the 1(1)B(u), and the
      2(1)Ag pi-pi* excited states of trans-butadiene. The large weight bonding schemes
      are shown to be a qualitative indicator for the known photochemistry of
      butadiene. The remarkable stability of the Arduengo carbene is discussed by
      obtaining bonding schemes that indicate a stabilizing delocalization of the pi
      electrons. We illustrate that the large weight bonding schemes are in line with
      the observed reactivity of the Arduengo carbene.

PMID- 14696071
TI  - A finite B-spline basis set for accurate diatomic molecule calculations.
AB  - A finite basis set particularly adapted for solving the Hartree-Fock equation for
      diatomic molecules in prolate spheroidal coordinates has been constructed. These
      basis functions have been devised as products of B-splines times associated
      Legendre polynomials. Due to the large number of B-splines, the resulting set of
      eigenfunctions is amply distributed over excited states. This gives the
      possibility of using these basis sets to calculate sums over excited states,
      appearing in various orders of perturbation theory. As an illustration, the
      second-order corrections to the ground-state energy of some atoms and diatomic
      molecules with closed electron shells have been calculated.

PMID- 14696072
TI  - New developments in the symmetry-adapted algorithm of the Polarizable Continuum
      Model.
AB  - We present recent developments in the symmetry implementation of the Polarizable
      Continuum Model (PCM). The structure of the matrix, which defines the PCM solvent
      response, is examined, and we demonstrate how this matrix can be transformed to a
      block diagonal form where each block belongs to different irreducible
      representations of the molecular point group. This development is especially
      important at the Multi-configurational Self-Consistent Field (MCSCF) level where
      symmetry is needed to avoid problems with symmetry breaking in the wave function
      and facilitate the optimization of electronic excited states. Moreover, although
      only the totally symmetric part of the solvent interaction is needed for energy
      calculations, in response or perturbation theory calculations of molecular
      properties, other irreps play an important role and the classification of solvent
      interaction terms by irrep is, therefore, desirable. In addition, the use of
      symmetry reduces the computational cost. The implementation presented here is
      illustrated with a series of calculations of absorption and emission processes in
      solution on the diazines pyrazine, pyrimidine, and pyridazine. These calculations
      allow us to illustrate both formal aspects of the implementation such as the
      choice of active spaces based on orbital symmetry as well as practical aspects
      such as the speed-up of the calculation.

PMID- 14696073
TI  - QM/MM study of aqueous solvation of the uranyl fluoride [UO2F4(2-)] complex.
AB  - The aqueous solvation of the uranylfluoride complex [UO(2)F(4) (2-)] was studied
      using full quantum mechanical (QM) and hybrid QM/molecular mechanics (MM)
      methods. Inclusion of a complete first solvation shell was found necessary to
      reproduce the experimentally observed heptacoordination of uranium. An efficient
      and accurate computational model is proposed that consists of structure
      optimization of the coordinated uranium complex as QM region, followed by single
      point full QM calculations to compute relative energies. This method is proven
      feasible for studies of large solvated actinide complexes.

PMID- 14696074
TI  - Calculation of affinities of peptides for proteins.
AB  - Several methodologies were employed to calculate the Gibbs standard free energy
      of binding for a collection of protein-ligand complexes, where the ligand is a
      peptide and the protein is representative for various protein families. Almost 40
      protein-ligand complexes were employed for a continuum approach, which considers
      the protein and the peptide at the atomic level, but includes solvent as a
      polarizable continuum. Five protein-ligand complexes were employed for an all
      atom approach that relies on a combination of the double decoupling method with
      thermodynamic integration and molecular dynamics. These affinities were also
      computed by means of the linear interaction energy method. Although it generally
      proved rather difficult to predict the absolute free energies correctly, for some
      protein families the experimental ranking order was correctly reproduced by the
      continuum and all-atom approach. Considerable attention has also been given to
      correctly analyze the affinities of charged peptides, where it is required to
      judge the effect of one or more ions that are being decoupled in an all-atom
      approach to preserve electroneutrality. The various methods are further judged
      upon their merits.

PMID- 14696075
TI  - Automated docking of highly flexible ligands by genetic algorithms: a critical
      assessment.
AB  - An improved version of the fragment-based flexible ligand docking approach SEED
      FFLD is tested on inhibitors of human immunodeficiency virus type 1 protease,
      human alpha-thrombin and the estrogen receptor beta. The docking results indicate
      that it is possible to correctly reproduce the binding mode of inhibitors with
      more than ten rotatable bonds if the strain in their covalent geometry upon
      binding is not large. A high degree of convergence towards a unique binding mode
      in multiple runs of the genetic algorithm is proposed as a necessary condition
      for successful docking.

PMID- 14696076
TI  - Theoretical study on the rate constants for the C2H5 + HBr --> C2H6 + Br
      reaction.
AB  - The reaction C(2)H(5) + HBr --> C(2)H(6) + Br has been theoretically studied over
      the temperature range from 200 to 1400 K. The electronic structure information is
      calculated at the BHLYP/6-311+G(d,p) and QCISD/6-31+G(d) levels. With the aid of
      intrinsic reaction coordinate theory, the minimum energy paths (MEPs) are
      obtained at the both levels, and the energies along the MEP are further refined
      by performing the single-point calculations at the PMP4(SDTQ)/6
      311+G(3df,2p)//BHLYP and QCISD(T)/6-311++G(2df,2pd)//QCISD levels. The calculated
      ICVT/SCT rate constants are in good agreement with available experimental values,
      and the calculate results further indicate that the C(2)H(5) + HBr reaction has
      negative temperature dependence at T < 850 K, but clearly shows positive
      temperature dependence at T > 850 K. The current work predicts that the kinetic
      isotope effect for the title reaction is inverse in the temperature range from
      200 to 482 K, i.e., k(HBr)/k(DBr) < 1.

PMID- 14696077
TI  - Theoretical model of internal rotation in monosubstituted derivatives of
      furfural.
AB  - The present work explores the effect of substitution in all free positions of
      furfural on conformational preferences of formyl group by using ab-initio
      calculations at the MP2/6-31G(p,d) level of theory. Theoretical modeling was made
      in vacuo. The selected substituents were -CH(3), NH(2), NO(2) and F groups in 3,
      4, 5 and ipso carbonyl positions. Geometries of all derivatives were analyzed and
      it is ascertained that substitution has not important consequences on furan ring
      geometry. Differences of energy between OO-cis and trans conformers and energy
      barriers between them are described and extreme cases are explained. Interesting
      features appear in the cases of -NH(2) and -NO(2) groups, and particularly when
      the 3 and ipso carbonyl positions are substituted. Variations in energy barriers
      are correlated with variations in C2-C6 distances for the transition states and
      planar forms. Substitution effect on Mulliken charges are analyzed and related
      with internal rotation energy barriers and differences between conformers.

PMID- 14696078
TI  - Second-order atomic Fukui indices from the electron-pair density in the framework
      of the atoms in molecules theory.
AB  - Atomic Fukui indices, which are obtained from the electron density, have been
      previously shown to be useful in predicting which atoms in a molecule are most
      likely to suffer nucleophilic, electrophilic, or radicalary attacks. Here, we
      present a second-order generalization of these indices based on the electron pair
      density. We show how second-order atomic Fukui indices can be used to analyze the
      effects of electron loss or gain in several molecules from an electron pair point
      of view. Further, these indices also highlight which atoms or pairs of atoms are
      more likely to suffer nucleophilic, electrophilic, or radical attacks. In
      conclusion, second-order indices can complement first-order ones by affording
      relevant information on molecular reactivity from an electron pair perspective.

PMID- 14696079
TI  - Analysis of the intermolecular interactions between CH3OCH3, CF3OCH3, CF3OCF3,
      and CH2F2, CHF3.
AB  - The intermolecular interaction energy curves of CH(3)OCH(3)-CH(2)F(2),
      CF(3)OCH(3)-CH(2)F(2), CF(3)OCF(3)-CH(2)F(2), CH(3)OCH(3)-CHF(3), CF(3)OCH(3)
      CHF(3), and CF(3)OCF(3)-CHF(3) complexes were calculated by the MP2 level ab
      initio molecular orbital method using the 6-311G** basis set augmented with
      diffuse polarization functions. We investigate the fluorine substitution effects
      of both methane and dimethyl ether on intermolecular interactions. In addition,
      orientation dependence of intermolecular interaction energies is also studied
      with utilizing eight types of orientations. Our analyses demonstrate that partial
      fluorinations of methane make electrostatic interaction dominant, and
      consequently enhance attractive interaction at several specific orientations. On
      the contrary, fluorine substitutions of dimethyl ether substantially decrease the
      electrostatic interaction between ether and CH(2)F(2) or CHF(3); thus, there is
      no such characteristic interaction between the C-H of fluorinated methane and
      ether oxygen of CF(3)OCF(3) as conventional hydrogen bonding, due to reduced
      polarity of fluorinated ether. The combination of different pairs of the
      electrostatic interaction is therefore responsible for the intermolecular
      interaction differences among the complexes investigated herein and also their
      orientations.

PMID- 14696080
TI  - The National Cancer Data Base: a clinical surveillance and quality improvement
      tool.

PMID- 14696081
TI  - Molecular epidemiology: new insights into diagnosis and prognosis.

PMID- 14696082
TI  - Colon cancer screening: where have we come from and where do we go?

PMID- 14696083
TI  - Breast-conserving therapy (BCT) for early-stage breast cancer.
AB  - Several patient and tumor factors go into the decision process to determine
      whether a breast cancer patient is a good candidate for breast-conserving
      therapy. The patient must be seen by all disciplines before any therapeutic
      intervention. When used appropriately, breast-conserving therapy produces maximal
      disease control and improves quality of life in patients with early-stage breast
      cancer.

PMID- 14696084
TI  - Strategies for cancer gene therapy.
AB  - Gene therapy offers new opportunities for cancer treatment and prevention through
      the use of targeted, relatively nontoxic treatments that can identify, disable,
      and destroy malignant cells. This article reviews the principles behind oncogene
      inactivation, tumor suppressor gene replacement, inhibition of angiogenesis,
      immunopotentiation, molecular chemotherapy, and addition of drug resistance
      genes. The adcantages and limitations of viral and nonviral vectors for delivery
      of the therapeutic genes are presented.

PMID- 14696085
TI  - Risk factors for early death due to recurrence after liver resection for
      hepatocellular carcinoma: results of a multicenter study.
AB  - BACKGROUND AND OBJECTIVES: Recurrence after partial liver resection for
      hepatocellular carcinoma (HCC) is a major cause of death from this disease. To
      identify risk factors for early death from recurrence after liver resection for
      HCC. METHODS: All 547 patients in this study had greater than 1 year of follow-up
      after complete resection of HCC (1980-1999) at one of the four hepatobiliary
      centers in Japan, France, and the United States. Patients who died of recurrence
      < or =1 year post-resection and all of those alive at least 1 year were compared.
      Survival and clinicopathological factors associated with death from recurrence
      within 1 year of resection were analyzed. RESULTS: Overall postoperative
      mortality rate was 5%. In the first postoperative year, 123 (22%) patients died.
      Of these, 53 (43%) died of recurrence, 30 (24%) of postoperative complications,
      and 40 (33%) of liver failure/hemorrhage. On multivariate analysis, tumor size
      greater than 5 cm (P < 0.02; odds ratio, 3.0), multiple tumors (P < 0.01; odds
      ratio, 3.3), and greater than 5 mitoses per 10 high-power fields (P < 0.03; odds
      ratio, 3) were associated with increased risk of early death due to recurrence.
      CONCLUSIONS: These findings enable identification of patients with HCC who are at
      high risk for early death due to recurrence following potentially curative
      resection who might be candidates for adjuvant therapy trials.

PMID- 14696086
TI  - Oncolytic viral therapy for breast cancer with herpes simplex virus type 1 mutant
      HF 10.
AB  - BACKGROUND AND OBJECTIVES: Many genetically engineered viruses have been
      evaluated for their potential as therapeutic agents in the treatment of malignant
      tumors. We applied a spontaneously generated, highly attenuated herpes simplex
      virus (HSV) type-1 clone, HF10, to the treatment of breast cancer. In this study,
      we investigated the ability of HF10 to infect and lyse human and murine breast
      cancer cells in vitro and tested its efficacy in an immuno-competent animal model
      of breast cancer. METHODS: To assess the therapeutic efficacy of HF10 against
      subcutaneous tumors in vivo, mouse breast cancer cells were injected into the
      backs of mice, which were then treated with HF10. Tumor volume and survival rate
      were used as measures of the antitumor effect in the in vivo experiments. In
      vitro viral cytotoxity assays and replication assays were also performed in human
      breast cancer cell lines. RESULTS: In the in vivo study, tumor growth was
      suppressed and long-term survival rates were prolonged. HF10 was effective in
      producing cytolytic effects in vitro at various multiplicities of infection (MOI)
      in all cell lines tested. CONCLUSIONS: HF10 demonstrated antitumor effects in our
      animal model. The viral growth and oncolytic effect of HF10 in the human breast
      cancer cell line suggest that HF10 is potentially effective in the clinical
      treatment of human cancer. These results indicate that replication-competent HSV
      1 mutants hold significant promise as cancer therapeutic agents.

PMID- 14696087
TI  - Clinical significance of combination study of apoptotic factors and proliferating
      cell nuclear antigen in estimating the prognosis of hepatocellular carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most
      common recurrence diseases, which affects the patient's prognosis. The aim of
      this report is to evaluate recurrence risk after primary treatment by the
      combination study with the clinical features and immunohistological findings.
      METHODS: 153 removable HCCs were examined by immunohistochemical study of the
      proliferating cell nuclear antigen (PCNA), p53, or Bax. The relationships of
      these factors with histological grades, the presence of intra-hepatic metastasis
      (IM), tumor size, value of serum alpha-fetoprotein (AFP), and prognosis were
      studied. PCNA labeling index (LI) was calculated to count positive nuclei in
      1,000 cells. RESULTS: PCNALI was significantly higher in cancer and correlated
      with tumor size. PCNALI and the tumor diameter in themselves could be a good
      predictor for patient prognosis and the combination study of them was an even
      stronger indicator. The value of AFP was significantly higher in positive p53
      cases. The incidence of p53 was associated with histological types. The presence
      of IM was found in negative Bax cases of main tumors. The appearance of Bax was
      not correlated with histological types. The incidence of p53 or Bax was indicated
      to distinguish the patient prognosis of the lower grade histological cases, in
      which differences could not be found by the routine histological study.
      CONCLUSIONS: The combination study of the immunohistochemical findings and the
      clinical features could be one of the most important aids in interpreting the
      status of HCC.

PMID- 14696088
TI  - Control of intra-operative hemorrhage during excision of carotid body tumor.

PMID- 14696089
TI  - Computerized tomogram to design surgery for removal of large Merkel cell
      carcinoma of the buttock preserving the function of the extremity.

PMID- 14696090
TI  - Expression of a naturally occurring constitutively active variant of the
      epidermal growth factor receptor in mouse fibroblasts increases motility.
AB  - Tumor cell motility is one of the rate-limiting steps of invasion, which defines
      progression toward a more malignant phenotype. Elevated expression of epidermal
      growth factor receptor (EGFR) in many cancers is associated with progression of
      superficial to invasive forms of the disease. The naturally occuring type III
      mutant epidermal growth factor receptor (EGFRvIII) is a tumor-specific, ligand
      independent, constitutively active variant of the epidermal growth factor
      receptor. EGFRvIII is expressed frequently by a number of human solid tumours
      including those of the lung, breast, prostate, brain and ovary. Our study was
      designed to investigate the effect of EGFRvIII expression on cell motility and
      compare it to that of ligand-activated EGFR using transfected fibroblasts. We
      show here using time-lapse video recording that expression of EGFRvIII greatly
      enhances the motility of fibroblasts independently of ligand stimulation. In
      addition, expression of EGFRvIII caused a marked increase in the number of
      cellular protrusions (lamellipodia) and a reduction in the number of stress
      fibers and focal adhesions. The EGFR tyrosine kinase inhibitor, AG1478, and the
      MEK inhibitor, U0126, blocked these cellular effects of EGFRvIII. Two cell lines
      expressing different levels of EGFR were used for comparison. The low-expressing
      cell line responded to EGF treatment by increasing motility in a manner very
      similar to the motility induced by EGFRvIII. In contrast, the high-expressing
      cell line responded to EGF by detachment from the extracellular matrix and
      decreased motility. Cellular detachment was correlated to a high phosphorylation
      of PLC-gamma, whereas increased motility was correlated to a high level of ERK
      phosphorylation. Overall these results indicate that tumor-associated EGFR
      mutations might be critical for tumor cell motility, invasion and thus
      progression of disease.

PMID- 14696091
TI  - Elevated levels and distinct patterns of expression of A-type cyclins and their
      associated cyclin-dependent kinases in male germ cell tumors.
AB  - Aberrant expression of several key regulators controlling the G1/S phase of the
      cell cycle has been implicated in human male germ cell tumorigenesis. Given the
      critical role of cyclin A2 at both the G1/S and G2/M transitions and the
      essential role for cyclin A1 in male germ cell development, our present study
      focused on the involvement of the A-type cyclins in the transformation and
      progression of male germ cell tumors (GCTs). The expression of the A-type cyclins
      and their catalytic partners Cdk1 and Cdk2 was examined in all types and stages
      of human male GCTs, including carcinoma in situ(CIS), seminoma and non-seminoma
      GCTs, along with normal testis samples. Elevated levels of cyclin A2, Cdk1 and
      Cdk2 were detected in the majority of GCTs and were correlated with the
      invasiveness of the tumors (p < 0.05). Cyclin A1 expression was virtually
      undetectable in CIS and seminoma, but was aberrantly expressed in all non
      seminomatous GCTs. Cyclin A2 expression was strongly correlated with that of its
      catalytic partners Cdk1 and Cdk2 in all types of testicular tumors examined (p <
      0.05), whereas a strong correlation between cyclin A1 and Cdk1 or Cdk2 was only
      seen in non-seminomatous GCTs (p < 0.05). Histone kinase activities of cyclin
      A1/Cdks and cyclin A2/Cdks were found to be elevated in tumors. Our data suggest
      that aberrant expression of A-type cyclins and their Cdks is a significant factor
      in male germ cell tumorigenesis. The abundant ectopic expression of cyclin A1 in
      non-seminomatous GCTs and its absence in CIS and seminomas is likely linked to
      the tumor transformation and progression and may be relevant to clinical
      prognosis.

PMID- 14696092
TI  - Stat5a is tyrosine phosphorylated and nuclear localized in a high proportion of
      human breast cancers.
AB  - Signal transducers and activators of transcription (STATs) are latent cytoplasmic
      transcription factors that are activated and translocated into the nucleus after
      phosphorylation at a conserved tyrosine residue. Mouse model studies have
      demonstrated that activated Stat5a acts as a critical survival factor for normal,
      preneoplastic and malignant mammary epithelial cells. Very limited information is
      available, however, on the expression, tyrosine phosphorylation status and
      nuclear localization of Stat5a in human breast cancers. In our study, the pattern
      of Stat5a cellular localization was analyzed by immunohistochemistry in a series
      of 83 randomly selected primary human breast adenocarcinomas.
      Immunoprecipitation/Western blotting and immunohistochemistry assays employing
      different phospho-specific antibodies verified Stat5a tyrosine phosphorylation
      status. Stat5a was nuclear localized and tyrosine phosphorylated in 59 of 78
      (76%) breast cancers examined; 38 of 78 (49%) demonstrated Stat5a nuclear
      localization in more than 25% of the breast cancer cells within the
      adenocarcinomas. Nuclear localized Stat5a was associated positively with
      increased levels of histologic differentiation (p = 0.03). A statistically
      significant positive association with p27 nuclear localization also was
      identified (p = 0.05). No relationship was found between nuclear localized Stat5a
      and menopausal status, tumor size, ploidy, percentage of cells in S-phase, lymph
      node metastases, ER, ErbB2, nuclear localized p21 or nuclear localized
      Stat5b/Stat3. As its role in human breast cancer progression and response to
      therapy is defined, Stat5a could become a new molecular target for breast cancer
      therapy.

PMID- 14696093
TI  - p66Shc protein is upregulated by steroid hormones in hormone-sensitive cancer
      cells and in primary prostate carcinomas.
AB  - Members of Shc family conventionally serve as critical adaptors in tyrosine
      phosphorylation signal transduction pathways. p66(Shc) protein, a member of Shc
      family, is predominantly expressed in epithelial cells, whereas the regulation of
      its expression remains an enigma. We describe the effect of steroid hormones on
      the protein level of p66(Shc) and growth stimulation in hormone-sensitive human
      prostate, testicular and breast cancer cells. In DHT-treated androgen-sensitive
      prostate cancer LNCaP C-33 cells, the protein level of p66(Shc) was elevated by
      approximately 3-fold, correlating with increased cell growth. This DHT effect on
      p66(Shc) protein level and growth regulation was also observed in another
      androgen-sensitive prostate cancer cell line MDA PCa2b as well as 2 testicular
      cancer cell lines, Tera-1 and Tera-2 cells. Similarly, the female sex hormone
      estrogen had a stimulating effect on p66(Shc) protein level and proliferation in
      estrogen-sensitive MCF-7 breast cancer cells. The upregulation of p66(Shc)
      protein level by DHT was competitively abolished by Casodex, an androgen
      antagonist used to treat prostate cancer. Moreover, immunohistochemical analyses
      showed that the p66(Shc) protein level was significantly higher in primary
      prostate tumors than in adjacent non-cancerous cells (p < 0.05). The data
      collectively indicate that p66(Shc) protein levels correlate with steroid hormone
      stimulated cell growth and prostate carcinogenesis.

PMID- 14696094
TI  - hnRNP L enhances sensitivity of the cells to KW-2189.
AB  - Heterogeneous nuclear ribonucleoproteins (hnRNPs) are involved in several RNA
      related biological processes. We demonstrated hnRNP L as a candidate protein of
      DARP (duocarmycin-DNA adduct recognizing protein) by gel shift assay and amino
      acid sequencing. Stable transfectants of hnRNP L showed high sensitivity of the
      cells to the growth inhibitory effect of KW-2189, a duocarmycin derivative in
      vitro. Immunostaining of hnRNP L demonstrated differential intracellular
      localization of hnRNP L among human lung cancer cell lines. A transfection study
      using a series of deletion mutants of hnRNP L fused to indicated that the N
      terminal portions of RRM(RNA recognition motif)1, RRM3 and RRM2 are involved in
      localization of hnRNP L. We identified sequences in these portions that have high
      homology with the sequences of known NLS (nuclear localization signal) and NES
      (nuclear export signal). hnRNP L is a factor that determines the sensitivities of
      cancer cells to the minor groove binder, and overexpression and differential
      intracellular localization of hnRNP L are involved in its function in lung
      cancer.

PMID- 14696095
TI  - T-cell receptor Vbeta gene usage by T cells reactive with the tumor-rejection
      antigen SART-1 in oral squamous cell carcinoma.
AB  - We recently described that the SART-1(690-698) peptide could induce HLA-A24
      restricted cytotoxic T lymphocytes (CTLs), which recognize the SART-1(259) (+)
      tumor cells from peripheral blood mononuclear cells (PBMCs) of HLA-A24(+) cancer
      patients. In our study, in 5 of 14 HLA-A24(+) patients with oral squamous cell
      carcinomas (SCCs), CTLs could be induced with the SART-1(690-698) peptide from
      the PBMCs. In 2 of the patients from whom the highest CTL activities were
      induced, the T-cell receptor (TCR) Vbeta repertoire expressed by the SART-1(690
      698)-specific CTLs was found to be restricted and multiple Vbeta families were
      predominantly expressed in each patient. Although the predominant Vbeta families
      were different between the 2 patients, Vbeta7 was highly and commonly
      predominant. The same predominant Vbeta families were also detected in the tumor
      infiltrating lymphocytes (TILs) from each patient, and each Vbeta family
      contained one or more unique T-cell clonotypes. The unique T-cell clonotypes were
      found to be common between the TILs and SART-1(690-698)-specific CTLs from each
      patient, and especially 2 T-cell clonotypes with Vbeta7 were identical even in
      the 2 patients. One of the 2 T-cell clonotypes with Vbeta7 was detected in the
      TILs from 11 of 14 HLA-A24(+) patients and another was found in those from 8 of
      HLA-A24(+) patients, while none of 10 HLA-A24(-) patients demonstrated both T
      cell clonotypes. These results strongly suggest that the T-cell clonotypes with
      Vbeta7 are major TCR Vbeta genes expressed by SART-1(690-698)-specific CTLs.
      Furthermore, autologous tumor cells from one of the HLA-A24(+) patients
      stimulated the PBMCs and regional lymph node cells (LNCs) to expand the same T
      cell clonotypes as those in the SART-1(690-698)-specific CTLs. These results
      strongly suggest that the SART-1(690-698)-specific CTLs clearly accumulate in
      vivo, especially in the TILs, as a consequence of in situ antigenic stimulation
      by autologous tumor cells. The identification of the unique TCR Vbeta genes used
      by SART-1(259)-specific CTLs should help to improve the diagnosis of the specific
      immune response in patients with SART-1(259) (+) cancers, especially during
      anticancer immunotherapy.

PMID- 14696096
TI  - Improved immunogenicity of a self tumor antigen by covalent linkage to CD40
      ligand.
AB  - The interaction between the CD40 ligand (CD40L) and CD40 on antigen-presenting
      cells (APCs) is critical in promoting humoral and cellular immune responses.
      Agonistic anti-CD40 monoclonal antibody and soluble CD40L can act as powerful
      adjuvants to promote vaccination, but usually require repeated high-dose
      treatment. In this study, we demonstrate that the adjuvant effect of CD40L can be
      greatly improved by directly linking the antigen to CD40L. We constructed a
      fusion protein (Id-CD40L) consisting of the extracellular domain of CD40L and the
      idiotype (Id) protein, a weakly immunogenic tumor-specific antigen derived from
      the murine 38C13 B-cell lymphoma. The soluble Id-CD40L fusion protein retained
      CD40 binding activity and stimulated CD80 and CD86 upregulation and interleukin
      (IL)-12 production by macrophages. Immunization of mice with Id-CD40L without
      adjuvants resulted in high titers of anti-Id Abs dominated by the IgG1 isotype
      and protected the mice from subsequent lethal tumor challenge. In a dose-response
      study, we demonstrated that Id-CD40L elicited anti-Id antibody (Ab) responses in
      all immunized animals, even at a dose as low as 0.5 microg. Immunization with
      free Id and an IgG-CD40L fusion protein, which was identical in structure to Id
      CD40L but lost the Id determinant, resulted in significant lower anti-Id
      responses, indicating that physical linkage between the tumor antigen and CD40L
      was required for the optimal immune response. These results demonstrate that
      fusing CD40L to a candidate antigen can greatly improve the adjuvant activity of
      CD40L. This approach may be useful in developing vaccines for a variety of
      malignant and infectious diseases.

PMID- 14696097
TI  - mRNA expression of leukemia-associated antigens in patients with acute myeloid
      leukemia for the development of specific immunotherapies.
AB  - Specific immunotherapies for patients with acute myeloid leukemia (AML) using
      leukemia-associated antigens (LAA) as target structures might be a therapeutic
      option to enhance the graft-vs.-leukemia effect observed after allogeneic stem
      cell transplantation or to prolong a complete remission (CR) achieved by
      chemotherapy. Significant mRNA expression of LAA is a prerequisite for such
      immunotherapies. Here, previously characterized antigens associated with solid
      tumors (TAA) and newly characterized LAA were investigated for their expression
      in up to 60 AML patients and in leukemia cell lines. To investigate their
      specificity for leukemic blasts, the mRNA expression was also characterized in
      PBMN and CD34 positive cells of healthy volunteers and in a panel of normal
      tissues. The following antigens showed high mRNA expression in AML patients:
      MPP11 was detected in 43/50 (86%), RHAMM in 35/50 (70%), WT1 in 40/60 (67%),
      PRAME in 32/50 (64%), G250 in 18/35 (51%), hTERT in 7/25 (28%) and BAGE in 8/30
      (27%) of AML patients. Real-time RT-PCR showed a tumor-specific expression of the
      antigens BAGE, G250 and hTERT, as well as highly tumor-restricted expression for
      RHAMM, PRAME and WT1. The antigen MPP11 was overexpressed. These antigens might
      be candidates for immunotherapies of leukemia patients and, because of their
      simultaneous expression, also for polyvalent vaccines.

PMID- 14696098
TI  - Identification of bladder cancer antigens recognized by IgG antibodies of a
      patient with metastatic bladder cancer.
AB  - To identify tumor antigens useful for the diagnosis and treatment of patients
      with bladder cancer, a lambda phage cDNA library constructed from a high-grade
      bladder cancer cell line was screened with autologous serum from a patient with
      metastatic bladder cancer. Forty-eight distinct antigens were isolated. By
      evaluating the immunogenicity and the tissue-specific expression, KU-BL-1 and KU
      BL-2 were identified as immunogenic antigens with restricted tissue expression.
      KU-BL-1 was found to be a putative human lipoic acid synthetase with a metal
      binding site, CXXXCXXC, that was expressed in bladder cancer cell lines and most
      bladder cancer tissues, as well as normal bladder mucosa and testis tissues.
      Immunoglobulin (Ig)G antibody to KU-BL-1 was detected in 2 of 28 patients with
      bladder cancer, but not in 30 healthy individuals. KU-BL-2 was found to be a
      putative human kelch-like protein that was homologous to Drosophila kelch, with a
      BTB/POZ domain and kelch repeats. KU-BL-2 was expressed in bladder cancer cell
      lines, most bladder cancer tissues, testis and heart, but not in normal bladder
      mucosa. IgG antibody to KU-BL-2 was detected in 8 of 28 patients with bladder
      cancer, but not in 16 healthy individuals. Tumor reactive T cells were induced
      from peripheral blood mononuclear cells (PBMC) by stimulation with one of the HLA
      A24 binding KU-BL-2 peptides. Therefore, KU-BL-1 and KU-BL-2, which showed
      preferential expression in bladder cancer with restricted expression in normal
      tissues, as well as immunogenicity in multiple patients with bladder cancer, may
      be useful for the development of diagnostic and therapeutic methods for patients
      with bladder cancer.

PMID- 14696099
TI  - Two new trifunctional antibodies for the therapy of human malignant melanoma.
AB  - Trifunctional antibodies are able to redirect T cells and Fcgamma receptor(+)
      accessory immune cells to tumor targets. The simultaneous activation of these
      different classes of effector cells results in efficient killing of the tumor
      cells by different mechanisms such as phagocytosis and perforin-mediated
      cytotoxicity. Here, we introduce 2 new trifunctional antibodies specific for
      human melanoma. These trifunctional antibodies recognize with one binding arm CD3
      on human T cells. The other binding arm is directed against melanoma-associated
      proteoglycans or melanoma-associated gangliosides (GD2 as well as GD3). They
      mediate specific lysis of various melanoma cell lines in correlation with the
      level of antigen expression in short-term cytotoxicity experiments. A combination
      of the 2 trifunctional antibodies was equally or even more efficient. Moreover,
      they induced a strong Th1 cytokine pattern with high amounts of IFN-gamma and low
      or no IL-4. Accordingly, CD4(+) and especially CD8(+) T cells expanded, whereas B
      cells, NK cells and monocytes decreased. The cytokine response was up to 16-fold
      higher when tumor cells were present. IFN-gamma reached cytotoxic concentrations
      for SK-MEL-23 melanoma cells. The induction of a T-cell-activatory and melanoma
      cell-inhibitory cytokine milieu together with the redirection of T-cell- and
      accessory cell-mediated cytotoxicity are interesting features of these
      trifunctional antibodies. They may be a new option for the therapy of human
      malignant melanoma.

PMID- 14696100
TI  - Grape seed extract inhibits advanced human prostate tumor growth and angiogenesis
      and upregulates insulin-like growth factor binding protein-3.
AB  - Dietary intake of many fruits and vegetables has been shown to be associated with
      reduced risk of cancer. We investigated the in vivo efficacy of grape seed
      extract (GSE, patented as Traconol) against prostate cancer (PCA) and associated
      molecular events. Athymic nude mice were implanted with hormone-refractory human
      prostate carcinoma DU145 cells and fed with 100 and 200 mg/kg/day (5 days/week)
      doses of GSE for 7 weeks. At the end of experiment, tumors were
      immunohistochemically analyzed for cell proliferation, apoptosis and
      angiogenesis. Our data show that GSE feeding strongly inhibited tumor growth that
      accounted for 59-73% (p < 0.001) inhibition in tumor volume and 37-47% (p < 0.05)
      decrease in tumor weight at the end of the experiment. It did not show any
      significant change in body weight gain profile and diet consumption.
      Immunohistochemical analysis of tumors showed that GSE decreases proliferation
      index by 51-66% (p < 0.001) and increases apoptotic index by 3-4-fold (p <
      0.001). CD31 staining for endothelial cells, showed decrease in intratumoral
      microvasculature in GSE-fed group of mice. Control tumors showed 64.0 +/- 1.6
      CD31 positive cells/400x field compared to 23.2 +/- 0.9 and 15.7 +/- 0.08 (p <
      0.001) CD31 positive cells in 100 and 200 mg/kg doses of GSE-treated tumors,
      respectively. GSE strongly inhibited (47-70%, p < 0.05) vascular endothelial
      growth factor (VEGF) secretion in conditioned medium by DU145 cells. Recently,
      the circulating level of insulin-like growth factor binding protein (IGFBP)-3 is
      shown to inversely related with PCA risk, growth and prognosis. Consistent with
      this, we observed 6-7-fold (p < 0.001) increase in tumor-secreted levels of IGFBP
      3 after GSE feeding. In other immunohistochemical studies, compared to controls,
      tumor xenografts from GSE-fed groups of mice showed a moderate decrease in VEGF
      but an increase in IGFBP-3 levels. These findings suggest that GSE possesses in
      vivo anticancer efficacy against hormone-refractory human PCA, which is
      associated with its antiproliferative, proapoptotic and antiangiogenic activities
      together with upregulation of IGFBP-3.

PMID- 14696101
TI  - The role of type of tobacco and type of alcoholic beverage in oral
      carcinogenesis.
AB  - Incidence rates of oral and oropharyngeal cancers (oral cancer) in Spain are
      among the highest in Europe. Spain has a population heavily exposed to various
      types of tobacco and alcoholic beverages but the role and impact of tobacco type
      and beverage type in oral carcinogenesis remain controversial. To estimate the
      independent and joint effects of tobacco smoking and alcohol drinking habits on
      the risk of developing oral cancer, we carried out a multicenter, hospital-based,
      case-control study in Spain. Data from 375 patients newly diagnosed with cancer
      of the oral cavity or oropharynx and 375 matched control subjects were analyzed
      using multivariate logistic regression procedures. All exposure characteristics
      of amount, duration and cessation of both tobacco smoking and alcohol drinking
      were strongly associated with cancer risk following a dose-dependent
      relationship. At equal intake or duration levels, black-tobacco smoking and
      drinking of spirits were both associated with a 2- to 4-fold increase in cancer
      risk compared to blond tobacco smoking or drinking of wine or beer, respectively.
      While ever exposure to smoking only or drinking only was associated with a
      moderate and nonsignificant increase in cancer risk, a history of simultaneous
      exposure to both habits was associated with a 13-fold increase that was
      compatible with a synergistic effect model (p-value for interaction: 0.008).
      Exposure to black tobacco smoking and/or drinking of spirits may account for up
      to 77% of oral cancer occurrence in Spain. Both black tobacco smoking and
      drinking of spirits place individuals at a very high risk of developing oral
      cancer. Simultaneous exposure to tobacco and alcohol consumption increases oral
      cancer risk in a synergistic fashion, even when consumption levels are moderate.
      These results underline the importance of type of tobacco and alcohol
      concentration in oral carcinogenesis.

PMID- 14696102
TI  - A comparison of reproductive risk factors for CIS lesions and invasive breast
      cancer.
AB  - A differential effect of reproductive factors on the incidence of carcinoma in
      situ of the breast (CIS) and invasive cancer may indicate that hormonal factors
      related to reproductive history not only influence the initial steps towards
      breast cancer but also preinvasive malignant lesions. A comparison of
      reproductive factors was performed using a population-based cohort of 1.5 million
      Danish women born between 1935 and 1978. Between 1983 and 1998, 15,590 cases of
      invasive breast cancer and 871 cases of CIS were identified using a database with
      extensive clinical information. Number of births and age at first birth were
      similarly associated with the risk of being diagnosed with ductal carcinoma in
      situ (DCIS) compared to invasive breast cancer [RR(DCIS)(per
      birth)/RR(invasive)(per birth) = 1.03(0.93-1.14), RR(DCIS)(per 5yr)
      /RR(invasive)(per 5yr) = 1.06(0.96-1.17)]. Also, the short-term risk the first 10
      years after birth was similar for DCIS and invasive cancer [RR(DCIS)
      /RR(invasive) = 0.90 (0.74-1.09)]. Additional analyses were performed according
      to characteristics of the DCIS lesion (size, malignancy grade, noncomedo or
      comedo type). In conclusion, our observations do not support the theory that
      reproductive history is associated with progression from noninvasive to invasive
      breast cancer.

PMID- 14696103
TI  - Non-attendance in breast cancer screening is associated with unfavourable socio
      economic circumstances and advanced carcinoma.
AB  - Our first objective was to assess changes in non-attendance, proportion of
      advanced breast cancer and survival in Malmo Mammographic Service Screening
      Program, MMSSP, compared to a former trial, Malmo Mammographic Screening Trial,
      MMST. Our second objective was to describe non-attenders in MMSSP in socio
      economic terms and risk for advanced breast cancer compared to attenders.
      Information from hospital and national registers was used to identify 33,800
      women invited to service screening in MMSSP 1990-93. Attendance rates at first
      screening, the proportion of advanced breast cancers (Stage II-IV) and survival
      among non-attenders in MMSSP were compared to the non-attenders and with the
      control group of the former trial, MMST. Various socio-economic factors were
      assessed as potential predictors of non-attendance in MMSSP. Odds ratios (OR) and
      95% confidence interval (CI) were computed. Incidence of breast cancer during a
      10-year-period, relative risks and 95% CI among non-attenders compared to
      attenders in MMSSP were computed. Attendance rates were significantly lower in
      MMSSP but a lower proportion of advanced breast cancers and a somewhat better
      survival among breast cancer cases (not significant) was seen in non-attenders in
      MMSSP compared to MMST. In MMSSP non-attendance was associated with being
      unmarried, being born abroad, being not currently employed, crowded housing
      conditions and low income. Incidence of advanced breast cancer was significantly
      higher among non-attenders than among attenders. Attendance has decreased over
      time and potential reasons are discussed. Stage distribution and survival among
      non-attenders seem to have improved. Several socio-economic factors predict non
      attendance and non-attenders are at higher risk for advanced breast cancer.

PMID- 14696104
TI  - Do younger female breast cancer patients have a poorer prognosis? Results from a
      population-based survival analysis.
AB  - Younger women who develop breast cancer are hypothesized to have poorer survival
      rates than women who develop it at a later stage in life. Several studies have
      suggested that differences in biologic characteristics of breast cancer in
      younger (premenopausal) and older (postmenopausal) women may account for the
      prognostic variation. This population-based cohort study reports on survival
      rates of breast cancer in Singapore and examines the hypothesis that younger
      breast cancer patients have a poorer prognosis. A total of 6,397 breast cancer
      patients diagnosed from 1968 to 1992 were identified from the population-based
      cancer registry and followed up through 1997. Outcome measures were relative
      survival rates (RSRs) calculated using Hakulinen's method and excess hazards
      ratios (HRs) derived from a regression model based on relative survival. The 2-,
      5- and 10-year RSRs were worse among those aged > 75 (65%, 48% and 39%,
      respectively). The best survival rates were seen among those aged 40-44 (84%, 67%
      and 56%). Patients younger than 35 years faired reasonably well (79%, 60% and
      50%). When the data were stratified according to clinical stage and calendar
      year, the highest risk of excess deaths was found in women > or = 75 years old.
      In patients with localized cancer and/or regional metastases, those in the 35-39
      age group had the lowest excess risk. In patients with distant metastases, those
      younger than 35 years of age had the lowest excess risk of death. At the
      population level, younger women (< 45 years) with breast cancer in Singapore have
      higher relative survival rates.

PMID- 14696105
TI  - Age, sexual behavior and human papillomavirus infection in oral cavity and
      oropharyngeal cancers.
AB  - There are few well-established patient risk factors associated with human
      papillomavirus (HPV) infection in cancers of the oral cavity and oropharynx. The
      purpose of this study was to determine if there were significant different risk
      factors and tumor characteristics between HPV-positive and HPV-negative cancer
      cases. HPV was evaluated in cancer tissue and exfoliated oral cells of 193 oral
      cavity/oropharynx cancer patients using PCR and direct DNA sequencing. A patient
      questionnaire collected information about risk factors, sexual practices and
      medical history. The prevalence of HPV high-risk (HR) types was 20% in cancer
      cases. Three types were identified: HPV-16 (87%), HPV-18 (3%) and HPV-33 (11%).
      Risk factors for HPV-HR included younger age (< or = 55 years vs. > 55 years;
      adjusted OR = 3.4; 95% CI = 1.6-7.3) and younger-age cases who had more lifetime
      sex partners (adjusted OR = 3.8; 95% CI = 1.4-10.1), practiced oral-genital sex
      (adjusted OR = 4.3; 95% CI = 1.8-10.4) or oral-anal sex (adjusted OR = 19.5; 95%
      CI = 3.4-113). Compared to HPV-negative cancers, HPV-HR cancers were more likely
      to have a positive HPV-HR exfoliated oral cytology test (adjusted OR = 7.8; 95%
      CI = 3.4-18.4), later stage (adjusted OR = 3.0), nodal involvement (adjusted OR =
      4.1) and advanced grade (adjusted OR = 3.0). This study shows new evidence that
      the prevalence of oncogenic mucosal HPV is higher in younger-age oral
      cavity/oropharynx cancer cases whose sexual practices are typically associated
      with sexual transmission of the virus. HPV detection also appears to be an
      indicator of advanced disease characteristics that may require different clinical
      treatment for this subset of patients. An exfoliated oral cytology test for HPV
      was a significant predictor of HR types in the cancers, suggesting that an oral
      rinse may provide an early biomarker of infected tumors.

PMID- 14696106
TI  - Serum concentrations of IGF-I, IGFBP-3 and c-peptide and risk of hyperplasia and
      cancer of the breast in postmenopausal women.
AB  - Experimental evidence suggests that insulin and insulin-related growth factors
      may play a role in breast pathology through their mitogenic and anti-apoptotic
      effects on breast cells. Our objective was to assess the relationship between
      serum concentrations of insulin-like growth factor-I (IGF-I), its major binding
      protein (IGFBP-3), the ratio IGF-I:IGFBP-3, c-peptide (a marker of insulin
      secretion) and the ratio c-peptide:fructosamine (a marker of insulin resistance)
      and the risk of epithelial hyperplasia (an established breast cancer risk factor)
      and localized breast cancer among postmenopausal women. Study subjects were
      patients who provided serum before breast biopsy or mastectomy in 3 hospitals in
      Grand Rapids, MI between 1977 and 1987. Two case groups, 186 subjects with
      epithelial hyperplasia of the breast and 185 subjects with localized breast
      cancer, were compared to 159 subjects with nonproliferative breast changes that
      have not been associated with increased breast cancer risk. Serum concentrations
      of IGF-I, IGFBP-3 and the ratio IGF-I:IGFBP-3 were not related to risk of either
      hyperplasia or breast cancer. For women in the highest quartile of c-peptide or
      of c-peptide:fructosamine compared to those in the lowest quartile, the odds
      ratios (ORs) for hyperplasia were 3.0 (95% confidence interval [CI] 1.4-6.5) and
      3.3 (95% CI 1.5-7.3), respectively (p trend = 0.02 and 0.02, respectively). The
      corresponding ORs for breast cancer were 1.5 (95% CI 0.7-3.0) and 1.6 (95% CI 0.8
      3.2), respectively (p trend = 0.35 and 0.25, respectively). Our results suggest
      that insulin and insulin resistance may play a role in breast pathology in
      postmenopausal women.

PMID- 14696107
TI  - Loading mitomycin C inside long circulating hyaluronan targeted nano-liposomes
      increases its antitumor activity in three mice tumor models.
AB  - The frequent overexpression of the hyaluronan receptors CD44 and RHAMM in cancer
      cells opens the door for targeting by the naturally-occurring high-M(r)
      hyaluronan. This is the first time effective in vivo tumor targeting is reported
      for mitomycin C (MMC) loaded inside nano-sized hyaluronan-liposomes (denoted tHA
      LIP). The severe adverse effects of free MMC made it a rational candidate for an
      effective targeted carrier. In vitro, loading MMC inside tHA-LIP increased drug
      potency 100-fold, in cells overexpressing, but not in cells underexpressing,
      hyaluronan receptors. Both types of liposomes were non-toxic and reduced MMC
      related toxicity in healthy C57BL/6 mice. In 3 tumor models, BALB/c bearing C-26
      solid tumors; C57BL/6 bearing B16F10.9 or (separately) D122 lung metastasis, tHA
      LIP were long-circulating, 7-fold and 70-fold longer than nt-LIP and free MMC,
      respectively. tHA-LIP-mediated MMC accumulation in tumor-bearing lungs was 20% of
      injected dose, compared to 0.6% and 4% with free drug and nt-LIP, respectively.
      Tumor-free lungs showed low accumulation, irrespective of drug formulation. Key
      indicators of therapeutic responses, tumor progression, metastatic burden and
      survival, were superior (p < 0.001) in animals receiving MMC-loaded tHA-LIP, no
      treatment, MMC-loaded nt-LIP and free drug. In conclusion, tHA-LIP perform as
      tumor-targeted carriers, with promising prospects for treatment of tumors
      overexpressing hyaluronan receptors.

PMID- 14696108
TI  - Evaluation of the ability of digital infrared imaging to detect vascular changes
      in experimental animal tumours.
AB  - Infrared imaging has frequently been used in the past to detect changes in skin
      surface temperature associated with breast cancer. Usually a 1-2 degrees C
      elevation in skin surface temperature is observed at the tumour periphery, and it
      has been proposed that this change is due to hypervascularity resulting from
      tumour-associated angiogenesis. In our study, we used the rat mammary
      adenocarcinoma 13762 MAT, a tumour that has been used to identify antiangiogenic
      drugs, to investigate whether infrared imaging can detect angiogenesis in
      malignant tumours. If successful, it was hoped that this technique would
      represent a simple, noninvasive, procedure for monitoring the activity of
      antiangiogenic drugs. It was found that, unlike breast cancer patients, no tumour
      associated increase in skin surface temperature was observed, but a constant and
      highly significant reduction in temperature was noted that was independent of
      tumour size and was produced by relatively small tumours (>/= 0.5 cm in
      diameter). The explanation for this effect is unclear but it may be due to the
      poorly vascularised nature of rapidly growing tumours. Nevertheless, our study
      indicates that the peripheral temperature elevation reported in breast cancer
      patients is unlikely to be due to hypervascularity resulting from tumour-induced
      angiogenesis. An alternative explanation is that the temperature increase is due
      to a chronic inflammatory response around developing breast tumours. With
      increasing evidence that inflammation can enhance tumour growth and is associated
      with a poor prognosis, this suggestion implies that infrared imaging may have
      considerable prognostic value.

PMID- 14696110
TI  - Pathogenetic mechanisms of upper aerodigestive tract cancer in alcoholics.

PMID- 14696111
TI  - Chemoprotective effect of caffeic acid phenethyl ester on promotion in a medium
      term rat hepatocarcinogenesis assay.
AB  - Caffeic acid phenethyl ester (CAPE), a natural honeybee product exhibits a
      spectrum of biological activities including anti-microbial, anti-inflammatory,
      antioxidant and anti-tumoral actions. CAPE is also chemopreventive against
      intestinal, colon and skin cancer. Our aim was to extend the study of its
      chemoprotective features to the promotion of hepatocarcinogenesis. Male Wistar
      rats were subjected to a protocol under a modified promotion regimen of the
      resistant hepatocyte model. The altered hepatic foci (AHF) were quantitatively
      analyzed by histochemistry and image processing. When given during promotion,
      CAPE (20 mg/kg) decreased the expression of number and area gamma-glutamyl
      transpeptidase (GGT) positive AHF by 91% and 97%, respectively. When GGT
      expression was analyzed by RT-PCR, CAPE drastically decreased and prevented
      expression of almost all GGT transcripts at this stage of the carcinogenic
      process. Glutathione S-transferase placental form (GST-P), another protein marker
      for preneoplastic lesions was measured by Western blot and a decrease of 82% was
      observed. Additionally, we evaluated the effect of CAPE on the expression of
      nuclear factor NF-kappaB and found an 85% decrease in nuclear localization of the
      p65 subunit of NF-kappaB; however, their repressor, IkappaBalpha was not
      modified. Our results showed that CAPE given during promotion in
      hepatocarcinogenesis protects against induction of GGT-positive AHF, GST-P
      protein, GGT mRNA expression and translocation of p65. This phenomenon was
      independent of IkappaBalpha degradation.

PMID- 14696112
TI  - 2-methoxyestradiol induces caspase-independent, mitochondria-centered apoptosis
      in DS-sarcoma cells.
AB  - The anti-cancer potential of the natural estrogen metabolite 2-methoxyestradiol
      is associated with microtubuli interaction, anti-angiogenetic effects and
      inhibition of superoxide dismutase leading to apoptosis. The effectors of
      apoptotic signaling through 2-methoxyestradiol, however, are cell type-dependent.
      We investigated the effect of 2-methoxyestradiol on several events associated
      with apoptosis in rat DS-sarcoma cells. Translocation of the pro-apoptotic
      protein Bax to mitochondria was identified as an initial apoptotic event that was
      accompanied by a decrease in mitochondrial transmembrane potential and the
      formation of reactive oxygen species (ROS) followed by mitochondrial release of
      apoptosis inducing factor and endonuclease G. In addition, 2-methoxyestradiol
      treatment caused upregulation of death receptor ligands FasL and TNFalpha and
      induced caspase-8 activation. The pan caspase inhibitor Z-VAD-FMK did not
      suppress apoptotic cell death, however, indicating that the major pro-apoptotic
      effect of 2-methoxyestradiol is mediated by a caspase-independent mechanism.
      Furthermore, ROS do not seem to play a pivotal role in the toxic/apoptotic effect
      of 2-methoxyestradiol in DS-sarcoma cells because supplementation with various
      antioxidants provided only limit protection. Colony formation was not affected by
      antioxidants. Therefore, in DS-sarcoma cells, the breakdown of mitochondrial
      integrity with the subsequent release of mitochondrial nucleases is the main
      factor in 2-methoxyestradiol mediated cell death.

PMID- 14696113
TI  - 3-OH flavone inhibition of epidermal growth factor-induced proliferaton through
      blocking prostaglandin E2 production.
AB  - Epidermal growth factor (EGF) has been shown to induce proliferation in cells,
      however, the role of prostaglandin E(2) (PGE(2)) plays in EGF-induced
      proliferation in still unclear. EGF and PGE(2) showed proliferation responses in
      epidermoid carcinoma cell A431 by MTT and [(3)H] thymidine incorporation assay.
      Activation of the EGF receptor and extracellular signal-regulated protein kinases
      (ERK1/2), but not p38 and JNK, appeared 10 min after EGF treatment, whereas total
      amounts of ERK1/2, p38 and JNK remained unchanged in A431 cells, accompanied by
      induction of COX-2 and PGE(2) production. PD98059, a specific ERK1/2 inhibitor,
      inhibited EGF-induced proliferation with concomitant decreases in ERK1/2
      phosphorylation and COX-2/PGE(2) induction. Non-steroid anti-inflammatory drugs
      (NSAIDs) such as aspirin and diclofenac, a COX activity inhibitor, inhibited EGF
      induced proliferation by blocking PGE(2) production. The addition of PGE(2)
      reversed the inhibitory effects of PD98059, aspirin, and diclofenac on EGF
      induced proliferation. This suggests that COX-2/PGE(2) activation involves in EGF
      induced proliferation and locates at the downstream of ERK1/2 activation.
      Furthermore, the natural product, 3-OH flavone, showed the most-potent inhibitory
      activity on EGF-induced proliferation among 9 structurally-related compounds, and
      suppression of EGF receptor phosphorylation, ERK1/2 phosphorylation, and COX
      2/PGE(2) production by 3-OH flavone was identified. PGE(2) addition attenuates
      the inhibitory activity of 3-OH flavone on EGF-induced proliferation by MTT assay
      and colony formation by soft agar assay. Additionally, 3-OH flavone also showed
      more-specific inhibition on EGF- than on fetal bovine serum (FBS)-induced
      proliferation in A431 cells. Results of our present study provide evidence to
      demonstrate that PGE(2) is an important downstream molecule in EGF-induced
      proliferation, and 3-OH flavone, which inhibits PGE(2) production by blocking
      MAPK cascade, might reserve potential for development as an anti-cancer drug.

PMID- 14696114
TI  - Parathyroid hormone-related protein (PTHrP) is responsible for production of bone
      metastasis, but not visceral metastasis, by human small cell lung cancer SBC-5
      cells in natural killer cell-depleted SCID mice.
AB  - We previously established an osteolytic bone metastasis model with multiorgan
      dissemination in natural killer (NK) cell-depleted severe combined
      immunodeficient (SCID) mice using human small cell lung cancer cells (SBC-5),
      which highly express the parathyroid hormone-related protein (PTHrP). In our
      present study, we evaluated the role of PTHrP on bone metastasis by SBC-5 cells
      using anti-PTHrP neutralizing antibody (Ab). Anti-PTHrP Ab did not affect the
      proliferation or cytokine production of SBC-5 cells in vitro. Repeated
      intravenous injection with anti-PTHrP Ab inhibited the formation of bone
      metastasis in a dose-dependent manner, while the same treatment had no
      significant effect on the metastasis to visceral organs (lung, liver, kidney and
      lymph node). In addition, treatment with anti-PTHrP Ab improved the elevated
      serum calcium level, associated with inhibition of osteolytic bone metastasis,
      suggesting that anti-PTHrP Ab inhibited bone metastasis via suppression of bone
      resorption probably by neutralizing PTHrP. These findings suggest that PTHrP is
      essential for bone metastasis, but not visceral metastasis, by small cell lung
      cancer SBC-5 cells.

PMID- 14696115
TI  - Regulation of carcinoma cell invasion by protein C inhibitor whose expression is
      decreased in renal cell carcinoma.
AB  - Protein C inhibitor (PCI), a member of the serine protease inhibitor family, is
      produced in various human tissues, including the liver, kidney and testis. In
      addition to inhibiting the anticoagulant protein C pathway, PCI also inhibits
      urinary plasminogen activator (uPA), which is a well-known mediator of tumor cell
      invasion. In the present study, to clarify the biologic significance of PCI in
      the kidney, we compared the expression of PCI between human renal cell carcinoma
      (RCC) tissue and nontumor kidney tissue. The PCI antigen level in RCC tissue was
      found to be significantly lower than in nontumor kidney tissue, and expression of
      PCI mRNA was detected in normal renal proximal tubular epithelial cells (RPTEC),
      but not in RCC or in an RCC cell line (Caki-1 cells). No differences were
      detected between the nucleotide sequence of the major cis-elements in the
      promoter region of the PCI gene from nontumor kidney and RCC tissues, RPTEC and
      Caki-1 cells, an RPTEC-derived RCC cell line. The in vitro invasiveness of Caki-1
      cells transfected with a PCI expression vector was significantly decreased
      compared to mock-transfected Caki-1 cells, and it was blocked in the presence of
      anti-PCI antibody. Since PCI itself did not affect the proliferation rate of Caki
      1 cells or cell expression of uPA in vitro, the effect of uPA, PCI, heat
      inactivated PCI and plasminogen activator inhibitor (PAI)-1 on the invasive
      potential of cultured RCC cells was evaluated. The in vitro invasiveness of Caki
      1 cells, which express uPA, was significantly enhanced by the addition of uPA,
      and it was inhibited by anti-uPA antibody, PCI and PAI-1, but not by heat
      inactivated PCI. In addition, uPA activity was significantly decreased and uPA
      PCI complex level was significantly increased in the culture medium of PCI
      expression vector-transfected Caki-1 cells as compared to mock-transfected Caki-1
      cells. These findings strongly suggest that PCI regulates the invasive potential
      of RCC cells by inhibiting uPA secreted by these cells. The results of our study
      suggest that PCI might be a potential therapeutic agent for inhibiting renal
      tumor invasion.

PMID- 14696116
TI  - The role of angiogenesis, vascular maturation, regression and stroma infiltration
      in dormancy and growth of implanted MLS ovarian carcinoma spheroids.
AB  - MLS ovarian epithelial carcinoma multicellular spheroids xenografted
      subcutaneously in CD-1 nude mice displayed growth delay, or dormancy, of up to 52
      days. In the study reported here, implanted MLS spheroids were used for testing
      the role of angiogenesis and vascular maturation in triggering the initiation of
      tumor progression. The kinetics and impact of neovascular maturation and
      functionality, in dormancy, and growth of MLS spheroid xenografts were studied
      noninvasively by BOLD contrast MRI. MR data were supported by histologic staining
      for biotinylated albumin as a blood pool marker and alpha-smooth muscle actin
      (alpha-SMA) as marker for perivascular mural cells. Although the tumor periphery
      showed higher levels of total and mature vasculature than normal skin, the
      fraction of mature out of the total vessels as detected by MRI vascular
      maturation index (VMI(MRI)) was significantly lower in the tumor both before and
      after tumor exit from dormancy. The neovasculature induced by the implanted
      spheroid was unstable and showed cycles of vessel growth and regression.
      Surprisingly, this instability was not restricted to the immature vessels, but
      rather included also regression of mature vessels. During dormancy,
      neovasculature was predominantly peripheral with no infiltration into the
      implanted spheroid. Infiltration of alpha-SMA positive stroma cells into the
      spheroid was associated with functional vascularization and tumor growth. Thus,
      stroma infiltration and vascular maturation are an important checkpoint linking
      the angiogenic switch with initiation of tumor progression.

PMID- 14696117
TI  - Decreased pyruvate kinase M2 activity linked to cisplatin resistance in human
      gastric carcinoma cell lines.
AB  - Resistance to anticancer drugs is a major obstacle preventing effective treatment
      of disseminated cancers. Understanding the molecular basis to chemoresistance is
      likely to provide better treatment. Cell lines resistant to cisplatin or 5
      fluorouracil (5-FU) were established from human gastric carcinoma cell lines SNU
      638 and SNU-620. Comparative proteomics involving 2-dimensional gel
      electrophoresis (2-DE) and matrix-associated laser desorption ionization-mass
      spectroscopy (MALDI-MS) was performed on protein extracts from these parental and
      drug-resistant derivative lines to screen drug resistance-related proteins.
      Pyruvate kinase M2 (PK-M2) was identified as a protein showing lower expression
      in cisplatin-resistant cells compared to parental cells. Consistent with this
      finding, PK-M2 activity was also lower in cisplatin-resistant cells. Suppression
      of PK-M2 expression by antisense oligonucleotide resulted in acquired cisplatin
      resistance in SNU-638 cells. Furthermore, PK-M2 activity in 11 individual human
      gastric carcinoma cell lines positively correlated with cisplatin sensitivity.
      Taken together, PK-M2 protein and activity levels were lower in cisplatin
      resistant human gastric carcinoma cell lines compared to their parental cell
      lines. Furthermore, suppression of PK-M2 expression using antisense
      oligonucleotides increased cisplatin resistance. These data clearly link PK-M2
      and cisplatin resistance mechanisms.

PMID- 14696118
TI  - HER-2 receptor expression, localization, and activation in colorectal cancer cell
      lines and human tumors.
AB  - The HER-2/neu oncogene encodes a 185 kD protein that is phosphorylated upon
      ligand binding to other HER/erbB members and regulates cell growth and
      differentiation. Given that HER-2 receptor blockade can inhibit the growth of
      colon cancer cell lines and tumor xenografts, we investigated the frequency,
      localization and phosphorylation status of HER-2 in colon cancer cell lines and
      in human tumors. Protein expression was analyzed in relation to mRNA levels, HER
      2 amplification, and clinicopathological variables. Colon cancer cell lines
      constitutively expressed HER-2 proteins and none showed HER-2 amplification by
      fluorescence in situ hybridization. Cell fractionation and immunoblotting showed
      HER-2 in both the membrane and cytosolic compartments. Primary colorectal
      carcinomas (n = 96) and their metastases (n = 25) were examined by
      immunohistochemistry. Strong membrane HER-2 staining was detected in 5 (5%) of
      primaries and in 3 (12%) metastases (p = 0.36). Membrane but not cytoplasmic
      localization was strongly associated with HER-2 gene amplification (p = 0.007).
      Cytoplasmic HER-2 staining was found in 61 (63.5%) of primary tumors and
      localization was confirmed by immunoelectron microscopy that also showed plasma
      membrane HER-2. Using real-time quantitative RT-PCR, HER-2 mRNA was increased in
      tumors with membrane compared to cytoplasmic staining (r = 0.66, p = 0.001).
      Cytoplasmic HER-2 was associated with tumor differentiation (p = 0.018), but not
      other clinicopathological variables. By immunoblotting, heterogeneity was seen in
      HER-2 levels with downregulation in 4 of 7 tumors relative to normal epithelia
      that uniformly expressed HER-2. Phosphorylated HER-2 was detected in
      approximately 50% of tumors and in normal mucosa. In conclusion, HER-2 is
      expressed constitutively in colon cancer cell lines and demonstrates relatively
      distinct localization patterns in human tumors. Strong membrane immunoreactivity
      is associated with high levels of HER-2 mRNA and gene amplification whereas
      cytoplasmic HER-2 is detected frequently and seems to be a marker of tumor
      differentiation.

PMID- 14696119
TI  - Recombinant single-chain antibody fusion construct targeting human melanoma cells
      and containing tumor necrosis factor.
AB  - Fusion constructs targeting tumor cells have significant potential applications
      against both solid tumors and hematologic malignancies. We developed a fusion
      construct of tumor necrosis factor (TNF) and a single-chain antibody (scFvMEL)
      recognizing the gp240 antigen on human melanoma cells. The scFvMEL/TNF construct,
      like TNF itself, was found to exist in solution primarily as a trimer of 45 kDa
      monomers (trimeric molecular weight = 135 kDa). The fusion construct bound
      specifically to gp240 antigen-positive but not to antigen-negative cells. The TNF
      component of the construct was biologically active (specific activity = 1 x 10(7)
      U/mg) compared with free TNF (specific activity = 2.6 x 10(7) U/mg) and was more
      cytotoxic to antigen-positive A375-M melanoma cells (IC(50) = 100 pM) than TNF
      alone (IC(50) = 1,000 pM) and, additionally, was active against AAB-527 melanoma
      cells (IC(50) = 20 nM) resistant to TNF itself (IC(50) > 1,000 nM). The augmented
      cytotoxicity was mediated by antibody-specific binding to the cell surface. Both
      A375-M and AAB-527 cells were shown to express TNFR1 and TNFR2 on the cell
      surface. The TNF moiety of the fusion construct was efficiently delivered into
      cells in time-dependent increase in cytosol as assessed by immunofluorescent
      staining of human melanoma cells. Radiolabeled scFvMEL/TNF localized effectively
      in human melanoma xenografts in nude (nu/nu) mice with a tumor:blood ratio of
      approximately 8 at 72 hr after administration. Our studies suggest that because
      of its unique biologic activity and low antigenic potential, scFvMEL/TNF makes an
      excellent cytotoxic protein for potential clinical treatment of human melanoma.

PMID- 14696120
TI  - Immunoscreening of a cDNA library from a lung cancer cell line using autologous
      patient serum: Identification of XAGE-1b as a dominant antigen and its
      immunogenicity in lung adenocarcinoma.
AB  - By serologic identification of antigens by recombinant expression cloning (SEREX)
      analysis using an autologous lung adenocarcinoma cell line, OU-LU-6, as a cDNA
      library source, we demonstrated that XAGE-1 was the dominant antigen recognized
      by serum from a patient. By immunoscreening, we obtained 38 positive cDNA clones
      consisting of 16 genes designated as OY-LC-1 to -OY-LC-16. OY-LC-1, represented
      by 18 clones, was identical to XAGE-1. OY-LC-2 to -16, represented by either a
      single or 2 clones, were identical to known genes shown to be ubiquitously
      expressed in various normal tissues. RT-PCR analysis showed that of 4 XAGE-1
      transcripts-XAGE-1a, b, c and d-XAGE-1b was expressed in OU-LU-6 dominantly.
      Furthermore, XAGE-1b mRNA was expressed in 4 of 10 lung cancer tissues, whereas
      no expression was observed in normal tissues. Of 4 XAGE-1b mRNA positive cancer
      tissues, 3 were adenocarcinoma and one was poorly differentiated squamous cell
      carcinoma. Of 32 sera from lung cancer patients, 8 sera were reactive with the
      XAGE-1b product. Those 8 sera were from patients with adenocarcinoma. These
      findings indicated strong immunogenicity of XAGE-1b in lung adenocarcinoma and
      suggested its potential use as a target for vaccine-based immunotherapies.

PMID- 14696121
TI  - Generation, immunologic characterization and antitumor effects of human
      monoclonal antibodies for carcinoembryonic antigen.
AB  - We generated fully human mAbs (HmAbs) to carcinoembryonic antigen (CEA) using the
      KM mouse, which carries a human chromosome 14 fragment containing the entire Ig H
      chain loci and human kappa L chain segments in the mouse genome. Forty-six
      hybridoma clones producing HmAbs to CEA were thus obtained by fusing the P3-U1
      mouse myeloma cells with splenocytes of the KM mice immunized with CEA. Among
      them, 22 clones produced HmAbs that reacted with CEA but not with 3 other CEA
      related cell adhesion molecule (CEACAM) family members, CEACAM1, CEACAM6 and
      CEACAM8. In 12 HmAbs examined, 8 were IgG4, 2 were IgG3, 1 was IgG2, and the
      other was IgG1. The affinity constants for CEA of these HmAbs were comparable to
      those of the previously prepared mouse anti-CEA mAbs (MmAbs). BIAcore analyses
      revealed that 1 and 2 of the 22 HmAbs react with 2 epitopes defined by MmAbs on
      the domain N and the domain A1 or B1 of CEA, respectively. In the presence of
      human complement in vitro, 2 HmAbs tested showed substantial cytotoxicity,
      namely, 50-65%, against CEA-expressing tumor cells. With human lymphokine
      activated killer cells in vitro, 3 HmAbs tested exhibited 40-65% Ab-dependent
      cell-mediated cytotoxicity against the tumor cells. Moreover, one of the HmAbs
      induced a significant inhibition of tumor growth when administered to mice
      xenografted with the CEA-expressing cells. Considering their lack of
      immunogenicity to humans, these CEA-specific HmAbs may be useful for
      immunotherapeutic approaches as well as for immunodiagnosis.

PMID- 14696122
TI  - Partial tyrosinase-specific self tolerance by HLA-A*0201-restricted cytotoxic T
      lymphocytes in mice and man.
AB  - The human tyrosinase (hTyr) (369-377) cytotoxic T lymphocyte (CTL) epitope is
      presented by malignant melanoma and various nontransformed cells in association
      with human leukocyte antigen (HLA)-A*0201 (A2.1) and used for vaccination-based
      immunotherapy of melanoma patients. Its mouse homologue, mTyr (369-377), is
      naturally processed and bound by A2.1 with equivalent efficacy and thus enabled
      us to explore the effect of self tolerance on Tyr-specific T cells in different
      lines of A2.1 transgenic (Tg) mice and man. We found that self Tyr-reactive CTL
      in Tg mice and, importantly, in man were affected by partial tolerance resulting
      in only residual T lymphocytes of higher avidity for self Tyr along with low
      avidity T cells to be present in the periphery. Immunizing mice with the
      xenogeneic nonself Tyr peptide facilitated the generation of self Tyr-reactive
      CTL. As compared to Tyr-reactive CTL induced by high amounts of the self Tyr
      epitope, however, the nonself antigen (Ag) had no effect on improving the avidity
      of self Tyr-specific mouse and human T cells. Depleting mice of CD25(+) T cells
      with and without CTL-associated Ag 4 (CTLA-4) blockade demonstrated that
      tolerance of Tyr-specific CTL was not regulated by CD4(+)CD25(+) T regulatory
      cells (Treg) or CTLA-4. Our studies have important implications for the design of
      anti-Tyr-based immunotherapeutics.

PMID- 14696123
TI  - Rescue of death receptor and mitochondrial apoptosis signaling in resistant human
      NSCLC in vivo.
AB  - Non small cell lung carcinoma (NSCLC) is a highly lethal malignancy that often
      becomes resistant to chemotherapy. To determine whether alterations in apoptotic
      signaling might contribute to such resistance, we established in vitro and in
      vivo models for sensitive and resistant human NSCLC. We found that resistance is
      due to multiple defects found in expression of CD95-L, CD95 and members of the
      Bcl-2 and IAP family, as well as caspase-8, -9 and -3 as examined by
      immunohistochemistry, Western blot analysis, gene array analysis and functional
      assays. Failure to activate death receptor, as well as mitochondrial apoptosis
      signaling, points to a central role of caspases. To restore apoptosis signaling
      we transfected NSCLC xenografts on nude mice with caspase-8 and -9. This
      treatment strongly induced apoptosis per se and sensitized the tumors to
      cisplatin-induced cell death. Thus, these findings indicate that re-expression of
      caspases might be an effective strategy to restore sensitivity for chemotherapy
      in NSCLC in vivo.

PMID- 14696124
TI  - Association of kallikrein expression in nipple aspirate fluid with breast cancer
      risk.
AB  - Human kallikreins (hK) 2, 3, 6 and 10 are expressed in breast and prostate
      tissue. hK2 and hK3 (prostate-specific antigen, PSA) are used to screen for
      prostate cancer. hK6 and hK10 are downregulated in breast cancer compared to
      normal breast tissue. We demonstrated that levels of PSA in nipple aspirate fluid
      (NAF) are lower in women with breast cancer than in normal women. We hypothesize
      that the expression of hK2, 3, 6 and 10 are related and important in detecting
      breast cancer. The goals of this study are to determine the level of expression
      of kallikreins in NAF and serum, the association of hK2, 3, 6 and 10 in NAF, and
      the association of each of the kallikreins with breast cancer. In NAF from 275
      women, hK3, 6 and 10 were detectable in >/= 90% and hK2 in 74% of samples
      analyzed. NAF levels were highest for hK6 and lowest for hK2, regardless of
      cancer and menopausal status. hK3 was detectable in 15/29 (52%) and hK2 in 0/29
      serum samples collected from 6 women. hK2 and hK3 were concentrated in NAF vs.
      matched serum. The 4 kallikreins were associated with the exception of hK2 with
      hK6 or hK10. PSA levels were higher in normal pre- than postmenopausal subjects
      (but not women with breast cancer), whereas levels of hK2, 6 and 10 did not
      differ by menopausal status. hK2 and PSA were associated with both pre- and
      postmenopausal breast cancer; hK6 and 10 were not. hK2 and PSA were more
      associated with pre- than postmenopausal breast cancer. Using logistic
      regression, PSA and menopausal status provided the best model of breast cancer
      prediction, with a sensitivity of 91% and specificity of 39%. In conclusion, 4
      kallikreins are expressed in NAF. hK2 and PSA, and hK6 and hK10 are highly
      associated. Higher premenopausal PSA levels suggest the influence of ovarian
      steroids. PSA shows the most promise in aiding in the early detection of breast
      cancer.

PMID- 14696125
TI  - Highly sensitive detection of the MGB1 transcript (mammaglobin) in the peripheral
      blood of breast cancer patients.
AB  - We describe a new one-step RT-PCR assay for the detection of the mammaglobin
      (MGB1) gene transcript in the peripheral blood of breast cancer patients. With
      this approach, the MGB1 transcript could be detected in the peripheral blood of
      22 of 54 (41%) breast cancer patients prior to any therapy. This method, using
      specific primers for cDNA synthesis, proved to be more sensitive (10(-6) to 10(
      11), usually 10(-7)) than previously reported methodologies. This increased
      sensitivity was achieved without compromising specificity, as the MGB1 transcript
      was not detected in 38 blood samples of healthy donors and in only 1 of 18 blood
      samples of patients presenting with hematologic malignancies. A positive
      correlation was seen between MGB1 positivity and breast cancer stage: 0/3 (0%) in
      stage 0, 3/13 (23%) in stage I, 6/17 (35%) in stage II, 5/10 (50%) in stage III,
      8/11 (73%) in stage IV (p = 0.003). The prognostic and therapeutic implications
      of MGB1 positivity by one-step RT-PCR in the peripheral blood of breast cancer
      patients, especially in clinically localized disease (stages I and II), should be
      evaluated after long-term clinical follow-up of these patients.

PMID- 14696126
TI  - Childhood leukemia and road traffic: A population-based case-control study.
AB  - To assess the effect of road traffic exhaust on the risk of childhood leukemia,
      we carried out a population-based case-control study in the Province of Varese,
      northern Italy, covered by a population-based cancer registry. All 120 incident
      cases from 1978-97 were included in the study. Four controls per case, matched by
      age and gender, were sampled from population files. As index of exposure to
      traffic exhaust we estimated the annual mean concentration of benzene outside the
      home using a Gaussian diffusion model. This model uses traffic density
      (vehicles/day) on nearby main roads, distance between roads and residence, and
      information on vehicle emissions and weather conditions to estimate benzene
      concentration. Compared to children whose homes was not exposed to road traffic
      emissions (<0.1 microg/m(3) of benzene as estimated by the model), the risk of
      childhood leukemia was significantly higher (relative risk [RR] = 3.91; 95%
      confidence interval [CI] = 1.36-11.27) for heavily exposed children (over 10
      microg/m(3) estimated annual average). For the intermediate exposure group (0.1
      10 microg/m(3)) the relative risk was 1.51 (95% CI = 0.91-2.51). These data,
      considered with other available evidence, suggest that motor traffic emissions
      can be involved in the etiology of childhood leukemia.

PMID- 14696127
TI  - Physical activity and renal cell cancer risk in a cohort of male smokers.
AB  - Few studies have examined exercise in relation to risk of renal cell cancer. We
      examined the association between leisure-time and occupational physical activity
      and renal cell cancer in a cohort of 29,133 male smokers 50-69 years of age in
      the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study. Physical
      activity was assessed at baseline using a self-administered questionnaire that
      inquired about usual level of physical activity during leisure-time and at work
      during the past year. Cox proportional hazards modeling was used to adjust
      simultaneously for known or suspected risk factors for renal cell cancer. During
      12 years (354,407 person-years) of follow-up, 210 incident cases of renal cell
      cancer were identified. In age-adjusted analysis, the RRs of renal cell cancer in
      increasing categories of leisure-time physical activity (light, moderate and
      heavy) were 1.0, 0.89 (95% CI = 0.67-1.17) and 0.38 (95% CI = 0.15-0.94),
      respectively (p-value for trend = 0.06). After adjustment for body mass index,
      energy intake, smoking, hypertension, education and fruit and vegetable intake,
      the multivariate RRs of renal cell cancer in increasing categories of leisure
      time physical activity (light, moderate and heavy), were 1.0, 0.89 (95% CI = 0.66
      1.19), and 0.46 (95% CI = 0.18-1.13) (p-value for trend = 0.12). Occupational
      physical activity was unrelated to renal cell cancer risk. These data suggest
      that recreational physical activity may play a role in the prevention of renal
      cell cancer in men.

PMID- 14696128
TI  - Modification effects of GSTM1, GSTT1 and CYP2E1 polymorphisms on associations
      between raw salted food and incomplete intestinal metaplasia in a high-risk area
      of stomach cancer.
AB  - Incomplete intestinal metaplasia (IM) is a precursor of stomach cancer. To
      identify risk factors of incomplete IM, a 2-stage survey was carried out in 1995
      among 1,485 residents in Matzu, an area with highest mortality from stomach
      cancer in Taiwan. There were 312 study subjects including 174 men and 138 women
      sampled for the gastroendoscopic examination of IM. Information on personal and
      familial history of stomach cancer, cigarette smoking, alcohol consumption and
      intake frequency of various salted food items were obtained by personal interview
      based on a structured questionnaire. Blood samples were collected from each
      participant. Four biopsies per subject were taken from all subjects at
      gastroendoscopic examination to diagnose the status of IM pathologically. The
      Helicobacter pylori in biopsies was detected by the histomorphological or
      immunochemistry method, and antibodies against H. pylori in serum by the enzyme
      linked immunosorbent assay. Plasma level of selenium was determined by atomic
      absorption spectrometry, plasma level of retinol, alpha-tocopherol, alpha
      carotene, and beta-carotene by high performance liquid chromatography, genotypes
      of glutathione S-transferase (GST) M1 and T1 and cytochrome P450 (CYP) 2E1 by
      polymerase chain reaction. The significant association between history of stomach
      cancer among first-degree relatives and incomplete IM was found (odds ratio [OR]
      = 2.50; 95% confidence interval [CI] = 1.15-5.43). There was no association
      between H. pylori infection and incomplete IM. Alcohol drinkers for >20 years had
      an elevated risk compared to non-drinkers (OR = 3.34; 95% CI = 1.19-9.39). No
      associations between incomplete IM and plasma levels of selenium, retinol, alpha
      tocopherol, alpha-carotene and beta-carotene were found. Salted food including
      salted meat, dehydrated salted vegetables and raw salted seafood consumed at ages
      of </=15 and 16-30 years old was associated with an increased IM risk with OR
      ranging from 2-3. More striking associations between incomplete IM and salted
      food intake were observed among subjects with genotypes of GSTM1 null, GSTT1 non
      null and CYP2E1 c1/c1. Our study suggests the importance of gene-environment
      interaction on the development of incomplete IM.

PMID- 14696129
TI  - Menstrual and reproductive factors and endometrial cancer risk: Results from a
      population-based case-control study in urban Shanghai.
AB  - The purpose of our study was to evaluate the association of menstrual and
      reproductive factors with the risk of endometrial cancer. In a population-based
      case-control study conducted in urban Shanghai, in-person interviews were
      completed for 833 women aged 30-69 years and an equal number of controls
      frequency-matched to cases by age. All cases were newly diagnosed with
      endometrial cancer between January 1, 1997 and December 31, 2001. The
      unconditional logistic regression model was employed to derive the adjusted odds
      ratios (ORs) of endometrial cancer and 95% confidence intervals (CIs) in relation
      to menstrual and reproductive factors. Earlier menarche age, particularly among
      premenopausal women, and later menopausal age were associated with an elevated
      risk of endometrial cancer. A clear dose-response relation between endometrial
      cancer risk and years of menstruation was observed (p for trend < 0.01). Compared
      to women ever having a pregnancy and women ever having had a live birth,
      respectively, nulligravity and nulliparity were both associated with a more than
      one-fold elevated risk of endometrial cancer. Both completed (OR = 3.02, 95% CI
      1.10-8.32 for women never having a complete pregnancy) and incomplete pregnancy
      (OR = 0.69, 95%CI 0.55-0.87) conferred a protective effect against endometrial
      cancer, and the protective effect appeared to increase with total number of
      pregnancies (p for trend = 0.01). The effect of pregnancy on endometrial cancer
      remained unchanged with increasing time since the last pregnancy. Stillbirth and
      age at first pregnancy was unrelated to endometrial cancer risk. Our study
      suggests that prolonged menstruation was related to an increased risk of
      endometrial cancer while pregnancy, including induced abortion, reduced the risk
      of endometrial cancer.

PMID- 14696130
TI  - Assessment of highly angiogenic and disseminated in the peripheral blood disease
      in breast cancer patients predicts for resistance to adjuvant chemotherapy and
      early relapse.
AB  - The assessment of tumor molecular features in combination with the detection of
      occult malignant cells may provide important clinical information, beyond the
      standard staging of breast cancer. Using a nested RT-PCR technique, we assessed
      prospectively the presence of cytokeratin-19 (CK19) mRNA positive cells in the
      blood of 100 operated patients with breast cancer before the initiation of
      adjuvant chemotherapy and local radiotherapy. Tissue samples were prospectively
      collected and analyzed for estrogen (ER) and progesterone (PgR) receptor, c-erbB
      2 overexpression, mutant-p53 and bcl-2 protein accumulation, proliferation index
      and microvessel density (MVD). CK-19 mRNA-positive cells were detected in the
      peripheral blood of 33% of patients. Simultaneous display of high intratumoral
      MVD and of CK-19 mRNA-positive cells, which characterized highly angiogenic and
      disseminated in the peripheral blood (HAD) disease was noted in 25% of patients.
      Detection of CK-19 positive cells was significantly associated with increased MVD
      (p = 0.002). In univariate analysis (median follow-up 30 months) CK19 mRNA
      detection and MVD were the most significant factors related to a short relapse
      free survival (RFS), (p < 0.0001). In multivariate analysis, CK19 positivity,
      high MVD and c-erbB-2 overexpression were the only significant and independent
      variables associated with relapse (p = 0.0005, 0.03 and 0.04, respectively).
      Patients with HAD had an expected relapse rate close to 70% vs. <5% in the
      remaining patients irrespectively of the used chemotherapy regimen. The
      simultaneous presence of high MVD and CK19-positive cells in the blood of
      patients with early breast is linked with poor prognosis, which cannot be
      improved with standard chemotherapy regimens.

PMID- 14696131
TI  - Long term consequences of the 1944-1945 Dutch famine on the insulin-like growth
      factor axis.
AB  - The insulin-like growth factor axis is highly responsive to nutritional status
      and may be involved as one of the underlying mechanisms through which caloric
      restriction could affect cancer risk. High levels of circulating insulin-like
      growth factor (IGF)-I, or IGF-I relative to IGF binding protein (IGFBP)-3 have
      been related to various human cancer types. In a group of 87 postmenopausal
      women, we found that childhood exposure to the 1944-1945 Dutch famine was
      associated with increased plasma levels of IGF-I and IGFBP-3, whereas IGFBP-1 and
      -2 levels were weakly decreased. These results are opposite to immediate
      responses seen under starvation and we hypothesize that this could indicate a
      permanent overshoot upon improvement of nutritional status after the famine.

PMID- 14696132
TI  - The efficacy of ritonavir in the prevention of AIDS-related Kaposi's sarcoma.
AB  - Angiogenesis is thought to play a major role in the development of Kaposi's
      sarcoma (KS), considered by many to be a hyperplastic disorder caused in part by
      local production of inflammatory cytokines. The antiangiogenic effects of
      protease inhibitors, in particular ritonavir, have been suggested in laboratory
      work to lead to regression of KS, and recent data have shown the importance of
      ritonavir as a model of pharmaceutical development. As our clinical cohort data
      has shown that non-nucleoside reverse transcriptase inhibitor-based regimens are
      not inferior to protease inhibitor-based therapy in the prevention of KS, we
      investigated the specific contribution of ritonavir to chemoprevention of this
      AIDS-defining illness. In a logistic regression analysis, we found that ritonavir
      based therapy confers no advantages compared to other regimens in the prevention
      of KS. This is consistent with data suggesting that regression of KS is mediated
      by an overall improvement in immune function and not by the effects of specific
      antiretrovirals.

PMID- 14696133
TI  - Fried potatoes and human cancer.

PMID- 14696135
TI  - Trends in survival for both histologic types of esophageal cancer in Switzerland.

PMID- 14696137
TI  - Diagnostic value of HepPar1, pCEA, CD10, and CD34 expression in separating
      hepatocellular carcinoma from metastatic carcinoma in fine-needle aspiration
      cytology.
AB  - Differentiating primary and metastatic hepatic malignancies can be diagnostically
      challenging in fine-needle aspiration cytology (FNAC). We compared four
      immunohistochemical (IHC) markers, pCEA, CD10, HepPar1, and CD34, in
      differentiating hepatocellular carcinoma (HCC) from metastatic carcinoma (MC) in
      FNAC specimens. Sixty cases of liver FNAC with their corresponding cell blocks
      were retrieved from the hospital computer system, including 30 HCC and 30 MC (15
      colon, 10 breast, and 5 pancreas). The diagnoses were confirmed by clinical
      follow-up and surgical resection or core needle biopsy. The direct cytologic
      smears were air-dried and Diff-Quik-stained, and alcohol-fixed and Papanicolaou
      stained. Cell block sections from the aspirates were immunostained for pCEA,
      CD10, HepPar1, and CD34. IHC on cytologic smears for HCC was performed on 10
      cases and compared with the cell block results. In HCC, CD10, and pCEA
      demonstrated the characteristic canalicular staining in 23/30 (77%) and 24/30
      (80%) of the cases, respectively; however, none of the MC showed a canalicular
      staining pattern. HepPar1 was positive in 26/30 (87%) of the HCC cases and one
      MC. CD34 stained sinusoidal endothelial cells in 27/30 (90%) cases of HCC and six
      MC. Our results demonstrate that the canalicular staining pattern for CD10 and
      sinusoidal staining pattern of CD34 are very specific, in addition to the high
      specificity and sensitivity of HepPar1 for HCC. Cell blocks were more informative
      in demonstrating the characteristic architecture and immunostaining pattern of
      the malignancy than the cytologic smears. An IHC panel consisting of pCEA, CD10,
      HepPar1, and CD34 is useful for confirming HCC in FNAC of the liver.

PMID- 14696138
TI  - ThinPrep for cytologic evaluation of follicular thyroid lesions: correlation with
      histologic findings.
AB  - Fine needle aspiration (FNA) is often the first step in management of a thyroid
      nodule. Although papillary carcinomas have distinctive features on conventional
      smears as well as ThinPrep preparations, cytopathologists rely on the
      architectural arrangement of cells to classify follicular lesions. The accuracy
      of ThinPrep in this regard has not been determined. We reviewed all thyroidectomy
      specimens from a 22-mo period that showed a follicular lesion and had one or more
      preoperative FNA. The architecture of the lesions on histology was classified as
      predominantly (>70%) macrofollicular (MA), predominantly microfollicular (MI),
      mixed (MX), or cystic (C). The presence of colloid, Hurthle cell features, cystic
      change, Hashimoto's thyroiditis, and nonspecific lymphocytic thyroiditis were
      also recorded. All FNA specimens were processed with the ThinPrep(R) method and
      were categorized as nondiagnostic, benign (MA or MX), indeterminate (due to
      suboptimal cellularity), or suspicious (consistent with a microfollicular or
      Hurthle cell neoplasm) based on cellularity, architectural arrangement of the
      follicular cells, and the presence or absence of colloid on FNA. Those cytologic
      specimens in the indeterminate category were subcategorized as suggestive of an
      MA, MX, or MI lesion if possible. Histocytologic findings were correlated using
      Fisher's exact test. A total of 95 patients with 115 FNAs were included in the
      study (mean age: 48 yr; 75 females and 20 males). Seven of the FNAs were
      nondiagnostic, 23 benign, 69 indeterminate (5, 8, and 30 favor MA, MX, and MI,
      respectively, 6 cyst contents and 20 not subclassifiable) and 16 suspicious. The
      cytohistologic correlation for architecture was significant (P = 0.003). The
      cytohistologic correlation of cystic change, Hurthle cell change, and the
      presence of colloid (large fragments of colloid and "tissue-paper-like material"
      on cytology vs. abundant colloid on histology) was highly significant (P < 0.001,
      < 0.001, and < 0.03, respectively). In conclusion, thyroid FNA with ThinPrep is
      useful in predicting the architectural pattern of follicular lesions. It is also
      reliable in predicting cystic change, Hurthle cell change, and the presence of
      colloid. Watery colloid is probably present as "tissue-paper-like material" in
      thyroid FNA ThinPrep preparations.

PMID- 14696139
TI  - Comparison of cytologic features of giant-cell tumor and giant-cell tumor of
      tendon sheath.
AB  - The cytologic features in twelve cases of giant-cell tumor (GCT) and five cases
      of giant-cell tumor of tendon sheath (GCTTS) diagnosed by fine-needle aspiration
      cytology (FNAC) are described. All of these cases were histopathologically
      confirmed. The aspirates of GCT are composed of a dual population of
      mononucleated spindle cell and multinucleated giant cells. The peripheral
      adherence of giant cells to the spindle cell is the feature of diagnostic
      significance in GCT. In GCTTS, the aspirate consists of a polymorphic population
      composed of mononuclear histiocyte-like cells, hemosiderin laden macrophages,
      foamy macrophages, and a few multinucleated giant cells. FNAC can be used as a
      diagnostic tool for an early and accurate detection of these two giant cell-rich
      lesions, since the cytologic features when evaluated in conjunction with the
      clinical and radiologic features are sufficiently diagnostic.

PMID- 14696140
TI  - Monophasic synovial sarcoma: a cytologic spectrum.
AB  - Synovial sarcoma (SS) is a high-grade sarcoma that can be diagnosed in cytology
      with certainty only when it presents with a biphasic pattern. Monophasic SS
      (MSS), however, is a diagnostic consideration when a uniform spindle cell
      population is present. The purpose of this study was to evaluate a series of
      cytologic cases of MSS and its cytologic presentation. Twenty-one FNAs of
      histologically confirmed MSS were reviewed. Specimens consisted of tissue
      fragments and single cells containing scant granular cytoplasm, medium-sized
      nuclei, and coarse chromatin. A monotonous spindle pattern with comma-shaped
      nuclei was present in 5 cases. Sixteen cases contained oval and spindled nuclei.
      Eight of these specimens contained round nuclei, and 5 of these cases showed
      prominent nucleoli and cohesive clusters, reminiscent of biphasic SS. We conclude
      that a spectrum of cytologic findings can be seen in MSS, including a secondary
      population of cells with morphology usually typical of biphasic SS.

PMID- 14696141
TI  - Review of the state of the art and recommendations of the Papanicolaou Society of
      Cytopathology for urinary cytology procedures and reporting : the Papanicolaou
      Society of Cytopathology Practice Guidelines Task Force.

PMID- 14696142
TI  - Cytology of low-grade endocrine neoplasms involving liver: a series of 24
      specimens, including 4 with hepatoid or glandular features.
AB  - Low-grade endocrine neoplasms (LGENs) involving the liver usually show typical
      endocrine features. Occasionally these tumors display cytologic characteristics
      that mimic hepatocellular carcinoma (HCC) or adenocarcinoma (ACA). Twenty-four
      liver FNABs from 22 patients were reviewed. Twenty specimens showed cytologic
      characteristics typical of LGENs, including small to medium-sized cells with salt
      and-pepper or granular chromatin, moderate to high N/C ratios, and inconspicuous
      or absent nucleoli. Plasmacytoid cells were observed in 19 cases.
      Immunocytochemical stains (ICCs) confirmed endocrine differentiation in 9 cases.
      4 FNABs were comprised of larger tumor cells that displayed cytologic features
      that overlapped with HCC or ACA, including transgressing or wrapping endothelium,
      moderate to abundant cytoplasm, and conspicuous nucleoli. LGENs involving the
      liver typically demonstrate characteristic cytologic features. Cases comprised of
      larger cells with abundant cytoplasm, conspicuous nucleoli, and transgressing or
      wrapping endothelium may pose diagnostic difficulties. ICCs and plasmacytoid
      morphology are beneficial in classifying the endocrine origin of these tumors.

PMID- 14696143
TI  - Fine-needle aspiration of parotid gland schwannomas mimicking pleomorphic
      adenoma: a report of two cases.

PMID- 14696144
TI  - Cytologic diagnosis of ossifying fibromyxoid tumor of soft tissue: a case report.
AB  - Ossifying fibromyxoid tumor (OFMT) of soft tissue is an uncommon, recently
      described neoplasm. It is usually, but not universally, a benign neoplasm and
      cases of metastatic so-called "malignant OFMT" have been reported. Although the
      histopathologic features of OFMT are well characterized, the same is not entirely
      true so far as the cytology literature is concerned. There are only three
      cytologic descriptions of OFMT to date to the best of our knowledge. A 62-year
      old woman presented with a subcutaneous well-circumscribed nodular soft tissue
      mass at the upper end of the shoulder. X-ray and computed tomography revealed an
      incomplete shell of calcification surrounding the nodular mass along with foci of
      ossification within it. Fine-needle aspiration (FNA) cytology showed round to
      polygonal to spindle shaped neoplastic cells arranged in clusters, cords, and
      small aggregates and lying discretely in a mucoid background. Some osteoid-like
      material was also seen. The tumor was completely excised and histopathologic
      examination confirmed the diagnosis of OFMT. OFMT should be considered as a
      possibility in FNA cytology of myxoid soft tissue tumor especially with
      radiologic evidence of ossification.

PMID- 14696145
TI  - Paratesticular congenital malignant rhabdoid tumor diagnosed by fine-needle
      aspiration cytology. a case report.
AB  - We report the FNA features of a congenital malignant extrarenal rhabdoid tumor
      (MERT) located in the right paratesticular area of a newborn full-term boy (39 wk
      gestation), with disseminated metastases in the liver and right parietal region.
      The diagnosis was suggested two days after birth by fine-needle aspiration biopsy
      (FNAB) of the parietal mass, which demonstrated an atypical large cell
      proliferation with vesicular nuclei, prominent nucleoli, and abundant cytoplasm
      exhibiting paranuclear dense inclusions. The diagnosis was confirmed by
      histopathologic and immunohistochemical examination of the primary paratesticular
      tumor. To the best of our knowledge, this is the third MERT reported in the
      paratesticular region, one of the few congenital extrarenal non-central nervous
      system cases, and the third congenital case (renal or extrarenal) primarily
      diagnosed by FNAB. We emphasize the characteristic cytologic features of a
      congenital rhabdoid tumor, which must be known by pathologists because of the
      clinical and prognostic implications. Diagn. Cytopathol. 2004;30:46-50.

PMID- 14696146
TI  - Primary pulmonary adenoid cystic carcinoma: report of a case diagnosed by fine
      needle aspiration cytology.
AB  - Adenoid cystic carcinoma of the lower respiratory tract is an uncommon tumor that
      can arise in the mainstem bronchus and often presents as an endobronchial mass
      lesion causing bronchial obstruction with post obstructive atelectasis and
      pneumonia. Exfoliative cytology is seldom useful in the diagnosis of primary
      bronchial adenoid cystic carcinoma, because these neoplasms usually have a
      submucosal location with often intact mucosa. Since most endobronchial adenoid
      cystic carcinomas are endoscopically visible, bronchoscope-guided fine-needle
      aspiration constitutes an excellent approach to establish a pathologic diagnosis.
      The fine-needle aspiration cytology of primary pulmonary adenoid cystic carcinoma
      has been rarely described. We report a case of primary adenoid cystic carcinoma
      of the lung having characteristic cytologic features and correlate with computed
      tomography, bronchoscopic, and histological findings. Bronchoscope-guided
      aspiration cytology provided a conclusive diagnosis of adenoid cystic carcinoma,
      which was further corroborated by histology in the pneumonectomy specimen. Diagn.
      Cytopathol. 2004;30:51-56.

PMID- 14696147
TI  - Microglandular hyperplasia has a cytomorphological spectrum overlapping with
      atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion
      (ASC-H).
AB  - We retrospectively evaluated cytological interpretations of conventional cervical
      smears in 48 cases of biopsy-proven microglandular hyperplasia and compared them
      with 15 negative controls. A glandular pattern was noted in all 48 cases but was
      predominant in 73% (35/48) of the cases. Immature metaplastic pattern was present
      in 71% (34/48) and was predominant in 27% (13/48). These features were not
      observed in negative control smears. 85% of cases (41/48) were interpreted as
      negative for epithelial cell abnormality. Two cases with predominantly glandular
      pattern (6%, 2/35) were interpreted as atypical glandular cells. Five cases with
      predominantly immature metaplastic pattern (38%, 5/13) showed checkerboard
      arrangement or rows of single cells with slightly larger atypical nuclei leading
      to interpretation as "atypical squamous cells-cannot exclude high-grade squamous
      intraepithelial lesion." The metaplastic cells with normoblast-like karyorrhectic
      apoptotic debris confined to the nuclear area were scattered among these cells in
      microglandular hyperplasia with metaplastic pattern.

PMID- 14696148
TI  - Carcinoid tumors of the lung: a diagnostic challenge in bronchial washings.
AB  - Bronchial washings are used routinely in the diagnosis of lung tumors. However,
      unlike other tumors, the diagnosis of bronchial carcinoids on bronchial washings
      is difficult. We reviewed 17 cases of histologically proven bronchial carcinoids
      from the files of the cytology laboratory over a period of 15 yr (1986-2001). The
      bronchial washings and histology sections of all the cases were reviewed
      separately by two independent observers and the results tabulated. Two cases had
      inadequate bronchial washings for evaluation and were excluded from the study. A
      growth was identified on bronchoscopy in 13 of 15 cases. Initial cytologic
      diagnoses were ?adenocarcinoma/?carcinoid and suspicious of carcinoid in one case
      each. However, on review, tumor was identified in 10 of 13 cases initially
      considered to be negative. The possible reasons for a false-negative report on
      initial cytology include the paucity of tumor cell fragments in the bronchial
      washings (5 of 12 cases showing only one to two tumor fragments) and their bland
      appearance, often being mistaken for benign columnar cells. This study highlights
      the potential pitfalls in the diagnosis of bronchial carcinoids on bronchial
      washings and underlines the importance of a diligent search in cases with high
      clinical suspicion and positive bronchoscopic findings.

PMID- 14696149
TI  - Melanotic neuroectodermal tumor of infancy (MNTI).

PMID- 14696150
TI  - Cutting balloon angioplasty of the popliteal and infrapopliteal vessels for
      symptomatic limb ischemia.
AB  - Options for lower limb percutaneous revascularization are limited especially for
      complex vessel obstruction. Cutting balloon angioplasty (CBA) has been described
      in the coronary literature as effective for complex disease. We analyzed our
      peripheral vascular database and report procedural outcomes along with the
      clinical success at a mean of 1-year follow-up in 73 patients with symptomatic
      lower limb ischemia undergoing CBA. CBA was successfully completed in all 73
      patients (93 vessels; 100%) with predilation necessary in 4% of vessels. Severe
      intimal dissection or inadequate hemodynamic result necessitated in adjunctive
      stenting in 20%. There were no incidents of vessel perforation or surgical target
      vessel revascularization. One patient (1.5%) died during the periprocedural
      period due to renal failure. After mean follow-up of 1 year (6-21 months), 89.5%
      of threatened limbs were salvaged. CBA is a safe and feasible option for the
      treatment of popliteal and infrapopliteal vessels.

PMID- 14696151
TI  - Subclavian artery stenting: factors influencing long-term outcome.
AB  - This study provides extended follow-up of a nonrandomized series of symptomatic
      patients who underwent subclavian stent-supported angioplasty (SSA) with emphasis
      on preprocedure factors that may have influenced outcome. The endpoints of
      mortality and restenosis were analyzed using backward stepwise logistic
      regression with the following clinical variables: coronary artery disease,
      hypertension, hyperlipidemia, smoking, diabetes mellitus, chronic obstructive
      pulmonary disease, chronic renal insufficiency/failure, and hypothyroidism.
      Restenosis is reported based on prospective serial noninvasive studies and/or
      angiography. Mortality was evaluated by retrospective database review and inquiry
      to the State Department of Health and Human Services' statistical registry in
      patients who were lost to follow-up. Over a 9-year period (mean follow-up, 36.1
      +/- 30.4 months; maximum observation, 109.5 months), 101 stents were placed in 91
      consecutive patients (37 male, 54 female). The mean age at intervention was 62.03
      +/- 9.3. The procedure was technically successful in 89 patients 97% (mean pre-
      and postoperative stenosis and pressure gradients were 90.2% +/- 9.4% vs. 3.7% +/
      6.6%, P < 0.001, and 59.9 +/- 35.2 vs. 0 mm Hg, P < 0.001, respectively), with
      13 minor complications and no immediate major complications. One patient died of
      unrelated causes within 30 days. Per Kaplan-Meier method, for years 1 through 5,
      the rates of overall patency were 96%, 91%, 86%, 77%, and 72%; likewise, overall
      patient survival was 93%, 88%, 8%4, 81%, and 76%. No clear predictors for
      restenosis were discovered, although a trend toward higher recurrence was noted
      in women (18.5% in female vs. and 8.6% in male; P > 0.05), but the same were less
      likely to die during follow-up (P > 0.001). Also, the presence of hypothyroidism
      (P = 0.004) and increasing age (P = 0.068) were positively correlated with all
      cause mortality. This study suggests that SSA is predictable, safe, and durable.
      The diagnosis of symptomatic subclavian disease is of prognostic importance, with
      age and male gender representing important predictors of all-cause long-term
      mortality. The strong association of increased mortality with hypothyroidism is
      difficult to discard and raises the question of a yet to be described thyroid
      steal phenomena.

PMID- 14696152
TI  - Vertebral artery stenting using distal emboli protection and transcranial
      Doppler.
AB  - Recent studies have shown the feasibility and safety of the percutaneous approach
      for the treatment of vertebrobasilar disease using either balloon angioplasty
      alone, coronary stents, or combined angioplasty followed by stenting. The major
      concern in performing percutaneous procedures for the treatment of obstructive
      disease of the vertebrobasilar circulation involves the risk of embolic
      phenomena. We describe the successful treatment of a symptomatic patient with
      bilateral vertebrobasilar disease utilizing a distal protection filter during
      stenting with simultaneous use of transcranial Doppler to measure
      microembolization and vertebral artery blood flow during the procedure.

PMID- 14696153
TI  - Penetrating ulcer of ascending thoracic aorta in syphilis.
AB  - Penetrating aortic ulcers (PAUs) are rare exotic pathological entities,
      classically located in the descending thoracic aorta. Their association with
      syphilis has never been reported. We describe a first case of a patient with
      cardiovascular syphilis presenting as PAU in the ascending aorta.

PMID- 14696154
TI  - Fallacy of thoracic side-branch steal from the internal mammary artery: analysis
      of left internal mammary artery coronary flow during thoracic side-branch
      occlusion with pharmacologic and exercise-induced hyperemia.
AB  - In some patients, myocardial ischemia after coronary artery bypass graft surgery
      has been attributed to a coronary steal phenomenon through a thoracic side branch
      originating from the left internal mammary artery (LIMA), even in the absence of
      subclavian or LIMA stenosis. To demonstrate that coronary flow through the LIMA
      is unchanged by occlusion of a LIMA side branch, we examined LIMA coronary flow
      velocity measurements (0.014" Doppler flow wire) in three patients at rest,
      during adenosine hyperemia, and again during hyperemia induced by left arm
      exercise before and again after the balloon occlusion of the thoracic side
      branch. For the three patients, no significant changes in resting or hyperemic
      flow were noted due to side-branch occlusion. Before side-branch occlusion,
      pharmacologic intra-arterial (adenosine) coronary flow reserve (hyperemic-to
      basal flow velocity ratio) was 2.6, 1.5, and 3.2 and exercise flow reserve was
      2.1, 1.3, and 1.2, respectively. After side-branch occlusion, pharmacologic
      coronary flow reserve was 2.5, 1.8, and 2.7 with exercise flow reserve of 1.8,
      1.1, and 1.3, respectively. Under most ordinary circumstances, thoracic side
      branch steal does not exist and that side-branch occlusion does not alter LIMA
      flow at rest or during pharmacologic or exercise-induced hyperemia. These data
      further suggest that a demonstration of the physiologic value of side-branch
      occlusion should precede surgical or percutaneous interruption of the thoracic
      artery in such patients.

PMID- 14696155
TI  - Editorial comment.

PMID- 14696156
TI  - Comparison of intracoronary vs. intravenous administration of abciximab in
      coronary stenting.
AB  - There have been animal and human studies looking at intracoronary (IC) use of
      abciximab with good short-term clinical outcomes. There exists no data comparing
      intracoronary with intravenous (IV) administration of abciximab beyond 30 days.
      We compared the clinical outcomes between the IC (n = 101) and IV (n = 72) group
      of patients. Patients who had coronary stenting and received abciximab were
      included in the study. All the patients received the standard systemic bolus dose
      of abciximab 0.25 mg/kg either via the IC or IV route, followed by a 12-hr IV
      infusion at 0.125 microg/kg/min. The 6-month composite endpoint of death or
      myocardial infarction was slightly higher in the IV (13.9%) than in the IC group
      (5.9%; P = 0.04). The frequency of bleeding complications was similar in both
      groups. The IC bolus route of abciximab may be superior to the intravenous route.
      Prospective randomized trials are warranted to validate these findings.

PMID- 14696157
TI  - Early experience with a novel plaque excision system for the treatment of complex
      coronary lesions.
AB  - The use of directional coronary atherectomy (DCA) in current practice has been
      limited. The SilverHawk System is a newly developed plaque excision device that
      aims to overcome the drawbacks of prior DCA platforms. The device was evaluated
      in a porcine coronary model and in a series of patients. Procedural variables
      along with outcomes were reviewed. Quantitative angiography (QCA) was performed
      and excised tissue fragments were weighed and examined histologically. In porcine
      cases, pretreatment MLD increased from 0.51 +/- 0.26 to 2.36 +/- 0.59 mm
      postdebulking and 19.9 +/- 7.6 mg of tissue was retrieved. In human cases,
      pretreatment MLD increased from 0.8 +/- 0.4 to 2.2 +/- 0.5 mm postdebulking and
      15.2 +/- 7.8 mg of tissue was retrieved without complications. These data show
      that the SilverHawk System may offer significant utility in treating a wide
      variety of complex coronary lesions.

PMID- 14696158
TI  - Predictors of vessel remodeling following directional coronary atherectomy.
AB  - The purpose of this study was to clarify predictors of vessel remodeling
      following directional coronary atherectomy (DCA). Negative remodeling after DCA
      leads to restenosis. However, little is known about the predictors of the vessel
      remodeling. Serial IVUS was performed in 43 lesions. The vessel remodeling was
      defined as adaptive if vessel area at follow-up minus postprocedure vessel area
      was > 0 mm2, or as constrictive if < 0 mm2. Adaptive remodeling occurred in 21
      (49%) lesions. Postprocedure percent plaque area was smaller in the adaptive
      group (32.9% +/- 5.7% vs. 45.5% +/- 8.8%; P < 0.005). At follow-up, vessel area
      was larger in the adaptive group. However, plaque area was similar between the
      two groups. As a result, lumen area was larger in the adaptive group.
      Multivariate analyses showed that postprocedure percent plaque area < 40% was the
      only predictor of adaptive remodeling (odds ratio, 6.68; P < 0.05).

PMID- 14696159
TI  - Assessment of anticoagulation using activated clotting times in patients
      receiving intravenous enoxaparin during percutaneous coronary intervention.
AB  - Enoxaparin is being used more frequently in patients undergoing percutaneous
      coronary intervention (PCI). In this study, we determined the effect of
      intravenous enoxaparin on activated clotting time (ACT) measurements in the
      setting of PCI. In 67 consecutive patients, either 1 mg/kg intravenous enoxaparin
      alone was given for anticoagulation or 0.75 mg/kg given in patients receiving
      eptifibatide. ACT was measured before and 5 min following enoxaparin
      administration. After 1 mg/kg enoxaparin (n = 22), mean ACT increased from 122 +/
      22 to 199 +/- 20 sec. After 0.75 mg/kg enoxaparin and eptifibatide (n = 45),
      mean ACT increased from 125 +/- 22 to 194 +/- 24 sec. The mean increase in ACT
      was 77 +/- 26 sec in the 1 mg/kg group and 69 +/- 23 sec in the 0.75 mg/kg group
      (both P values < 0.0001). Moreover, in a subgroup of 26 patients, there was an
      excellent correlation (r = 0.86) between ACTs and the ENOX test, a new point-of
      care test for assessing enoxaparin anticoagulation. None of the patients had
      transient abrupt closure, thrombus formation, major bleeding, or required urgent
      revascularization. Intravenous enoxaparin at clinically relevant doses with and
      without eptifibatide increases ACT levels at 5 min in patients undergoing PCI.
      These data suggest the ACT may be useful in the assessment of anticoagulation by
      enoxaparin.

PMID- 14696160
TI  - Percutaneous ulnar artery approach for primary coronary angioplasty: safety and
      feasibility.
AB  - Transradial approach in primary and rescue angioplasty may be advantageous with
      respect to the femoral access due to the lower incidence of vascular
      complications. Ulnar cannulation has been proposed for elective procedures in
      patients not suitable for transradial approach. We here report on 13 patients
      undergoing primary angioplasty performed using the transulnar approach. Ulnar
      access was finally obtained in 10 patients, sheath insertion time ranged from 2
      to 5 min, time from arterial puncture to vessel recanalization ranged from 21 to
      36 min. Primary angioplasty was successful in all patients. At 30-day echo color
      Doppler, all ulnar arteries were patent and with a physiologic pattern of flow.
      Subcutaneous hemorrhage of the forearm was observed in two patients, whereas
      hematoma, pseudoaneurysm, thrombus, and arterovenous fistula were not observed.
      In conclusion, transulnar access may represent an additional option in patients
      undergoing primary angioplasty when the radial artery access site is not
      available.

PMID- 14696161
TI  - Transradial coronary angiography in patients with contraindications to the
      femoral approach: an analysis of 500 cases.
AB  - The transradial approach to coronary angiography is considered by some to be a
      route of choice, by others to be a route that should be used only where there are
      relative contraindications to the femoral approach. We present the largest series
      to date of patients in whom transradial coronary angiography was undertaken
      specifically because of contraindications to the femoral approach. Since 1995,
      patients at this cardiothoracic center have been considered for a transradial
      approach to coronary angiography if there were relative contraindications to the
      femoral route. Data from 500 patients was prospectively collected. Patients were
      aged 66 +/- 9 years; 72% were male. Indications for the radial approach included
      peripheral vascular disease (305), therapeutic anticoagulation (77),
      musculoskeletal (59), and morbid obesity (32). Sixty-eight patients (14%)
      required a radial procedure following a failed femoral approach. Access was right
      radial 291 (58%), left radial 209 (42%). Eighteen operators were involved, but
      two operators undertook 355 (71%) of the cases. Catheter gauge was 6 Fr (n = 243;
      49%), 5 Fr (219; 43%), and 4 Fr (29; 6%). The procedure was successful in 463
      cases [92.6%; 88.2% for nonmajority vs. 94.4% (P < 0.05) for the two majority
      operators]. Success in males (93.6%) significantly exceeded that in females
      (90.1%; P < 0.05). In-catheter-laboratory duration was 45 +/- 17 min; fluoroscopy
      time, 7.5 +/- 6 min; radiation dose, 40 +/- 23 CGy. The procedure was without
      incident in 408 cases (82%). There were procedural difficulties in 18% of cases,
      including radial artery spasm (12%) and vasovagal response (5%). The incidence
      was higher with 6 Fr catheters (23%) than with 5/4 Fr (15%; P < 0.05). Major
      procedural complications occurred in three cases: brachial artery dissection in
      one and cardiac arrest in two. Postprocedure major vascular complications
      numbered three: claudicant pain on handgrip in one, ischemic index finger (with
      subsequent terminal phalanx amputation due to osteomyelitis) in one, and ischemic
      hand for 4 hr in one. Patients with contraindications to the femoral approach
      form a high-risk group. In these patients, transradial cardiac catheterization
      can be performed successfully and with a low risk of major complications. Minor
      adverse features remain frequent, occurring in one in five cases, though
      difficulties are minimized both with increasing operator experience and smaller
      sheath diameter.

PMID- 14696162
TI  - Comparison of transradial vs. transfemoral approach in the treatment of acute
      myocardial infarction with primary angioplasty and abciximab.
AB  - Compared to the femoral approach, the use of radial arterial access has been
      demonstrated to reduce the incidence of access site bleeding complications in
      staged procedures. The purpose of this study was to evaluate clinical outcomes
      comparing radial and femoral approaches in the treatment of acute myocardial
      infarction with primary angioplasty and the GP IIb/IIIa inhibitor abciximab.
      Between 15 September 1999 and 15 September 2002, we prospectively enrolled 119
      consecutive patients undergoing primary angioplasty with abciximab comparing
      radial (n = 64) and femoral (n = 55) access. In this nonrandomized study, freedom
      from major cardiac events at 1-month follow-up occurred in 62 (97%) and 52
      (94.5%) patients in the radial and the femoral groups, respectively (P = 0.19).
      There were no major access site bleeding complications in the radial group, as
      opposed to three (5.5%) in the femoral group (P = 0.03), all requiring
      transfusions, with surgical repair necessary in two. Uncomplicated clinical
      course occurred in 62 (97%) of patients in the radial group and 49 (89%) in the
      femoral group (P = 0.04). Total hospital length of stay was significantly higher
      in the femoral group (5.9 +/- 2.1 vs. 4.5 +/- 1.2 days; P = 0.05). Cannulation
      time (from patient arrival at the catheterization laboratory to the effective
      placement of arterial sheath) and procedural time were not significantly
      different in the radial and the femoral group (respectively 8.5 +/- 5.2 vs. 9.0
      +/- 5.8 min, P = 0.81, and 42 +/- 28 vs. 44 +/- 27 min, P = 0.74). Nevertheless,
      time of radiation (23.1 +/- 11 vs. 16.5 +/- 10.9 min; P = 0.01) and dose-area
      product (28,616 +/- 16,571 vs. 18,819 +/- 10,739 R. cm2; P = 0.01) were
      significantly higher in the radial group. In patients with acute myocardial
      infarction treated with primary angioplasty and abciximab, the transradial access
      is efficacious with fewer major access site complications than transfemoral
      access. Transradial approach produces a shorter length of stay, as compared to
      the transfemoral approach, although with longer times of radiation and higher
      dose-area product.

PMID- 14696163
TI  - Management of iatrogenic radial artery perforation.
AB  - The aim of this study was to evaluate a new protocol allowing coronary
      angiography to be performed transradially in spite of the occurrence of
      iatrogenic radial artery perforation during catheterization. Nine patients with
      iatrogenic radial artery perforation were managed conservatively by inserting a
      long arterial sheath in the damaged radial artery up to the brachial artery,
      after which the diagnostic and/or interventional procedures that had motivated
      transradial catheterization were completed via the protected radial artery.
      Radial angiography performed immediately thereafter showed no extravasation, and
      no major vascular complications developed during follow-up. The day after the
      procedure, two patients had asymptomatic radial occlusion, but the other seven
      patients had normal radial pulses and reversed Allen test responses showing
      normal perfusion. A conservative management technique, installation of a long
      arterial sheath not only promotes resolution of iatrogenic radial artery
      perforation but also allows the procedures motivating catheterization to be
      completed transradially.

PMID- 14696164
TI  - Anterior wall myocardial infarction in real world: does reperfusion strategy make
      any differences?
AB  - Some prospective randomized trials have established the superiority of primary
      percutaneous coronary intervention (PCI) over fibrinolytic treatment in patients
      with acute myocardial infarction (MI). These excellent PCI results are not
      duplicated in smaller hospitals where there may be delays in getting the cardiac
      catheterization team to the laboratory. This study aimed to compare the outcome
      of patients with anterior wall MI, without cardiogenic shock on admission,
      treated with primary PCI or thrombolytic therapy, in everyday practice. The data
      of all patients with MI hospitalized in all coronary care units operating in
      Israel during three consecutive national surveys was analyzed. A total of 1,038
      patients with anterior wall MI were treated by reperfusion (886 received
      thrombolytic therapy, 152 primary PCI). Overall, the outcome of patients treated
      using primary PCI was better compared to patients treated with thrombolysis, with
      68% relative risk reduction of 30-day mortality (mortality at 30 days: 2% vs.
      6.3%; P = 0.04). A subanalysis of patients according to age showed that the
      beneficial effect of primary PCI on mortality was mainly clustered among the
      younger. In our study, patients (especially younger than 75 years) with anterior
      wall MI allocated to primary PCI have a better clinical outcome.

PMID- 14696165
TI  - Retrospective image-based gating of intracoronary ultrasound images for improved
      quantitative analysis: the intelligate method.
AB  - Quantitative analysis of intracoronary ultrasound (ICUS) studies is performed on
      a series of tomographic cross-sectional ICUS images acquired during a motorized
      0.5 mm/sec catheter pullback. Catheter displacement in the vascular lumen during
      the cardiac cycle causes an anatomically shuffled ICUS study, which results in a
      sawtooth-shaped appearance of the coronary segment in longitudinal reconstructed
      views in quantitative coronary ultrasound software packages. This hampers contour
      detection and leads to a laborious time-consuming semiquantitative analysis
      process that may produce inaccurate results. To solve these problems, in the
      past, online ECG-gated acquisition hardware has been applied. This article
      describes a novel image-based gating method called Intelligate, which features
      automatic retrospective selection of end-diastolic frames from videotaped or
      digitally stored ICUS studies. Our evaluation shows that there are no
      quantitative differences between analysis results of hardware ECG-gated and
      Intelligated ICUS studies.

PMID- 14696166
TI  - Pulse transmission coefficient: a nonhyperemic index for physiologic assessment
      of procedural success following percutaneous coronary interventions.
AB  - Intracoronary pressure measurements and the determination of fractional flow
      reserve (FFR) after percutaneous coronary intervention (PCI) predict adverse
      events. Coronary lesions may impair the transmission of pressure waves across a
      stenosis, potentially acting as a high-frequency filter. The pulse transmission
      coefficient (PTC) is a nonhyperemic parameter that calculates the transmission of
      high-frequency components of the pressure signal through a stenosis. It was shown
      recently that PTC is highly correlated with FFR. This study was designed to
      examine the change of PTC as compared to FFR following PCI. Pressure signals were
      obtained by pressure guidewire in 27 lesions pre- and post-PCI and were analyzed
      with an algorithm that identifies the high-frequency component in the pressure
      signal. The PTC was calculated at baseline as the ratio between distal and
      proximal high-frequency components of the pressure waveform across the lesion.
      FFR measurements were assessed with intracoronary adenosine. There was a
      significant increase in PTC following PCI (0.15 +/- 0.17 at baseline vs. 0.84 +/-
      0.11 post-PCI; P < 0.001). Comparable changes were observed for FFR (0.58 +/-
      0.12 at baseline vs. 0.91 +/- 0.05 post-PCI; P < 0.001). PTC is a nonhyperemic
      parameter for physiologic assessment of coronary artery stenoses. Similar to FFR,
      PTC is significantly increased following PCI. Thus, it may serve as an adjunct
      index for the functional assessment of procedural success following PCI.

PMID- 14696167
TI  - Percutaneous intervention over the origin of a saphenous vein graft anastomosed
      with the St. Jude Medical Symmetry Aortic Connector System.
AB  - We describe a percutaneous intervention performed over the proximal anastomoses
      of an aortocoronary saphenous vein graft that had been attached to the aorta 3
      months before with the St. Jude Medical Symmetry Aortic Connector System.
      Technical aspects of procedure are discussed, and the experience previously
      reported in the literature related to this issue is reviewed.

PMID- 14696168
TI  - Damage to a covered stent by a thrombectomy device.
AB  - A 75-year-old with a history of coronary bypass grafting was found to have
      significant stenoses in a vein graft to the right coronary artery. Symbiot
      stents, with a polytetrafluoroethylene covering, were used to treat areas in the
      proximal and middle sections of the graft. The following day, she developed
      symptoms and signs consistent with an acute inferior infarction. The graft was
      found to be thrombosed. Thrombectomy was performed using an X-Sizer device,
      consisting of a helical cutter connected to a vacuum source. This resulted in
      damage to the stent lining, which led to jamming of the device and subsequent
      removal of a piece of the stent covering. Treatment was by way of deployment of a
      long stent within the damaged stent. Recovery was unremarkable. Caution or
      avoidance of this device appears warranted in the setting of covered stent
      procedures.

PMID- 14696169
TI  - Stent fracture and restenosis in the drug-eluting stent era.

PMID- 14696170
TI  - Angiographic and hemodynamic predictors for successful outcome of transcatheter
      occlusion of patent ductus arteriosus in infants less than 8 kilograms.
AB  - Transcatheter occlusion of patent ductus arteriosus (PDA) using Gianturco coils
      (GCs) has been performed for the past decade. However, little has been written
      regarding anatomical and hemodynamic predictors for successful occlusion of the
      PDA in infants. This report is to evaluate the outcome of transcatheter occlusion
      of PDA in symptomatic infants less than 8 kg and to assess predictors of
      successful occlusion. Retrospective review of catheterization charts and
      cineangiograms of 42 symptomatic infants who underwent cardiac catheterization
      for attempted transcatheter occlusion of their PDA was conducted. The hemodynamic
      and angiographic data evaluated included the length/diameter (L/D) ratio, defined
      as the length divided by the narrowest diameter of the ductus arteriosus, and
      preocclusion pulmonary artery pressures. Thirty-one out of 42 patients (74%) had
      successful occlusion. Twenty-nine out of 42 infants had an L/D ratio > 3. Of
      these, 26 (90%) had successful occlusion of their PDA. Thirteen out of 42
      patients had an L/D ratio < or = 3. Of these, 8 (62%) had unsuccessful occlusion.
      Complications encountered were transient loss of femoral arterial pulse (n = 6),
      coil embolization (n = 5), hemolysis (n = 2), and mild left pulmonary artery
      obstruction (n = 2). No permanent loss of femoral arterial pulse was noted. These
      complications resulted in no mortality and minimal morbidity. The L/D ratio was
      the strongest predictor of successful outcome, with an L/D ratio greater than 3.0
      being more amenable to transcatheter occlusion (odds ratio of 4.6). Other
      predictors for success included lower preocclusion systolic, diastolic, and mean
      pulmonary artery pressure and smaller ductal diameter. Our conclusion was that
      infants less than 8 kg with an L/D ratio > 3.0 can safely and successfully
      undergo transcatheter occlusion of their PDA using transcatheter coils.

PMID- 14696171
TI  - Antiphospholipid antibodies are common in patients referred for percutaneous
      patent foramen ovale closure.
AB  - Very little is known about any interaction between patent foramen ovale (PFO) and
      various hypercoagulable disorders that have been associated with cryptogenic
      stroke. Percutaneous PFO closure for secondary prevention of paradoxical
      thromboembolization is receiving increasing attention. Hypercoagulability may
      affect the potential risks and expected benefits of percutaneous PFO closure.
      Consecutive patients undergoing percutaneous PFO closure at a single center were
      screened for the presence of antiphospholipid antibodies, elevated
      lipoprotein(a), hyperhomocysteinemia, and dysfibrinogenemia. Sixteen of 34
      patients (47%) with complete arterial hypercoagulability screening had laboratory
      evidence of arterial hypercoagulability. Thirteen of these patients (38%) had
      antiphospholipid antibodies. Antiphospholipid antibodies appear to be common in
      patients referred for percutaneous PFO closure for secondary prevention of
      systemic thromboembolic events. Thorough testing based on established
      recommendations is warranted. Further studies are needed regarding the
      interaction between PFO and various hypercoagulable disorders that have been
      associated with cryptogenic stroke.

PMID- 14696172
TI  - Preoperative balloon dilatation of obstructed total anomalous pulmonary venous
      connection in a neonate.
AB  - Prompt recognition and early surgical correction are mandatory in neonates
      presenting with obstructed total anomalous pulmonary venous connection (TAPVC).
      Preoperative balloon angioplasty of obstructed TAPVC in a sick neonate is rarely
      reported. We describe successful short-term palliation with balloon angioplasty
      of a critically ill neonate with obstructed supracardiac TAPVC.

PMID- 14696173
TI  - Outcomes and alternative techniques for device closure of the large secundum
      atrial septal defect.
AB  - Outcomes of device closure of large and small secundum atrial septal defects
      (ASDs) as related to rim anatomy with the Amplatzer atrial septal occluder were
      compared. Rim adequacy (> or = 5mm) of the anterior, inferior, posterior, and
      superior rims was determined using transesophageal echocardiography. Balloon
      stretched defect size defined patients into two groups: group 1, < or = 25 mm (n
      = 138); group 2, > 25 mm (n = 34). Rim deficiency (n = 62) was more frequent in
      group 2 compared to group 1 (50% vs. 33%; P = 0.07), especially inferior rim
      deficiency (35% vs. 2%; P = 0.005). Device deployment was successful in group 1
      and group 2 (100% vs. 91%; P = 0.007). Unsuccessful deployment was associated
      with an ASD of > 25 mm (P = 0.007) and inferior rim deficiency (P = 0.001). At
      first follow-up (54 +/- 16 days), right ventricular systolic pressure had
      improved in both groups (P < 0.001). Closure of a large ASD associated with a
      lack of support in the inferior rim may warrant alternative strategies to
      position the device successfully.

PMID- 14696174
TI  - Transcatheter closure of a very large patent ductus arteriosus in a pregnant
      woman at 22 weeks of gestation.
AB  - Successful transcatheter closure of a large PDA in a pregnant patient is reported
      using the Amplatzer ductal occluder device. This procedure was safe and
      uncomplicated, obviating the need for surgery in this high risk patient.

PMID- 14696175
TI  - Transcatheter treatment of a large traumatic ventricular septal defect.
AB  - We report the first successful transcatheter closure of a large traumatic
      ventricular septal defect in a 16-year-old adolescent. The risks of standard open
      heart repair using cardiopulmonary bypass were felt to be prohibitive due to
      coexistent injuries. This case demonstrates the feasibility of transcatheter
      therapy for traumatic ventricular septal defects.

PMID- 14696176
TI  - Argatroban use during pediatric interventional cardiac catheterization.
AB  - Argatroban is a synthetic direct thrombin inhibitor that does not interact with
      or induce heparin-dependent antibodies. It is approved for use in adults for
      prevention and treatment of thrombosis associated with heparin-induced
      thrombocytopenia (HIT). It has been administered safely in adults with HIT during
      coronary interventions. There are no reports of argatroban use for
      anticoagulation in pediatric patients. The present case describes the use of
      argatroban during coil embolization of a Fontan fenestration in a child with a
      history of HIT. The patient received a single bolus dose of 150 microg/kg of
      argatroban at the onset of the intervention. The fenestration was successfully
      occluded with a detachable coil. The activated clotting time (ACT) was > 200 sec
      throughout the procedure. The ACT returned to baseline 72 min after the bolus. No
      complications occurred. This case demonstrates the safe and successful use of
      argatroban during a transcatheter intervention in a pediatric patient with a
      history of HIT. The use of argatroban is promising for anticoagulation in
      children who require an alternative to heparin.

PMID- 14696177
TI  - Transcatheter patch occlusion of heart defects.

PMID- 14696178
TI  - Hypothermia: a crack in the refrigerator door.

PMID- 14696179
TI  - The dilemma.

PMID- 14696180
TI  - Sequence and structural analysis of cellular retinoic acid-binding proteins
      reveals a network of conserved hydrophobic interactions.
AB  - Proteins in the intracellular lipid-binding protein (iLBP) family show remarkably
      high structural conservation despite their low-sequence identity. A multiple
      sequence alignment using 52 sequences of iLBP family members revealed 15 fully
      conserved positions, with a disproportionately high number of these (n=7) located
      in the relatively small helical region. The conserved positions displayed high
      structural conservation based on comparisons of known iLBP crystal structures. It
      is striking that the beta-sheet domain had few conserved positions, despite its
      high structural conservation. This observation prompted us to analyze pair-wise
      interactions within the beta-sheet region to ask whether structural information
      was encoded in interacting amino acid pairs. We conducted this analysis on the
      iLBP family member, cellular retinoic acid-binding protein I (CRABP I), whose
      folding mechanism is under study in our laboratory. Indeed, an analysis based on
      a simple classification of hydrophobic and polar amino acids revealed a network
      of conserved interactions in CRABP I that cluster spatially, suggesting a
      possible nucleation site for folding. Significantly, a small number of residues
      participated in multiple conserved interactions, suggesting a key role for these
      sites in the structure and folding of CRABP I. The results presented here
      correlate well with available experimental evidence on folding of CRABPs and
      their family members and suggest future experiments. The analysis also shows the
      usefulness of considering pair-wise conservation based on a simple classification
      of amino acids, in analyzing sequences and structures to find common core regions
      among homologues.

PMID- 14696181
TI  - Solution structure of ADO1, a toxin extracted from the saliva of the assassin
      bug, Agriosphodrus dohrni.
AB  - ADO1 is a toxin purified from the saliva of the assassin bug, Agriosphodrus
      dohrni. Because of its similarity in sequence to Ptu1 from another assassin bug,
      we did not assess its pharmacologic target. Here, we demonstrate by
      electrophysiologic means that ADO1 targets the P/Q-type voltage-sensitive calcium
      channel. We also determine the solution structure of ADO1 using two-dimensional
      NMR techniques, followed by distance geometry and molecular dynamics. The
      structure of ADO1 belongs to the inhibitory cystine knot (ICK) structural family
      (i.e., a compact disulfide-bonded core from which four loops emerge). ADO1
      contains a two-stranded, antiparallel beta-sheet structure. We compare the
      structure of ADO1 with other voltage-sensitive calcium-channel blockers, analyze
      the topologic juxtaposition of key functional residues, and conclude that the
      recognition of voltage-sensitive calcium channels by toxins belonging to the ICK
      structural family requires residues located on two distinct areas of the
      molecular surface of the toxins.

PMID- 14696182
TI  - Type I collagen N-telopeptides adopt an ordered structure when docked to their
      helix receptor during fibrillogenesis.
AB  - The in vitro rate and specificity of fibrillogenesis in type I collagen depends
      on the integrity of the amino (N)-telopeptide domain. In vivo an intact N
      telopeptide domain is also required for normal fibril assembly. Although Chou
      Fasman predictions and NMR studies suggested that a type I beta-turn could be
      induced in alpha1(I) N-telopeptide chains, computer modeling did not identify
      ordered structures. Nevertheless, X-ray analysis and electron tomography studies
      have shown that the N-telopeptide is in one of the most highly ordered fibril
      domains. This study was undertaken to determine if the docking of the N
      telopeptide to its helix receptor domain could induce the telopeptides to take up
      a specific conformation. With use of molecular modeling suite of programs, a (Gly
      Pro-Pro)(n) triple-helical structure was built on the basis of high-resolution X
      ray crystallographic coordinates and then replaced with the actual bovine
      collagen residues 924-938, the triple-helical alpha1(I)-N-telopeptide-receptor
      sequences. Energy minimization produced a modified triple-helical conformation.
      The bovine alpha1(I) N-telopeptide sequence was similarly minimized and docked to
      this receptor. The docking induced an ordered conformation with a stabilizing
      hydrogen bond in the N-telopeptide and, importantly, a reciprocal reordering of
      the triple-helical conformation in the binding domain. This docked structure
      placed Lys residues in both telopeptide and helix in the correct locations for
      cross-link formation. The modeling has been extended to the three-chain N
      telopeptide domain and finally to the construction of the Hulmes-Miller quasi
      hexagonal packing structure. Each N-telopeptide domain can form linkages with two
      adjacent, aligned helix receptor domains. The telopeptides and the order of
      staggering of the three chains in the helix play crucial roles in the packing and
      intrafibrillar cross-linking patterns and the relative azimuthal orientations of
      adjacent molecules in the fibril. The models confirm the high order in the N
      telopeptide 4D overlap zone.

PMID- 14696183
TI  - Crystal structure of the C67A mutant of isopentenyl diphosphate isomerase
      complexed with a mechanism-based irreversible inhibitor.
AB  - Isopentenyl diphosphate:dimethylallyl diphosphate (IPP:DMAPP) isomerase is a key
      enzyme in the biosynthesis of isoprenoids. The mechanism of the isomerization
      reaction involves protonation of the unactivated carbon-carbon double bond in the
      substrate. Analysis of the 1.97 A crystal structure of the inactive C67A mutant
      of E. coli isopentenyl diphosphate:dimethylallyl diphosphate isomerase complexed
      with the mechanism-based inactivator 3,4-epoxy-3-methyl-1-butyl diphosphate is in
      agreement with an isomerization mechanism involving Glu 116, Tyr 104, and Cys 67.
      In particular, the results are consistent with a mechanism where Glu116 is
      involved in the protonation step and Cys67 in the elimination step.

PMID- 14696185
TI  - Picosecond dynamics of the glutamate receptor in response to agonist-induced
      vibrational excitation.
AB  - Conformational changes of proteins are dominated by the excitation and relaxation
      processes of their vibrational states. To elucidate the mechanism of receptor
      activation, the conformation dynamics of receptors must be analyzed in response
      to agonist-induced vibrational excitation. In this study, we chose the bending
      vibrational mode of the guanidinium group of Arg485 of the glutamate receptor
      subunit GluR2 based on our previous studies, and we investigated picosecond
      dynamics of the glutamate receptor caused by the vibrational excitation of Arg485
      via molecular dynamics simulations. The vibrational excitation energy in Arg485
      in the ligand-binding site initially flowed into Lys730, and then into the J
      helix at the subunit interface of the ligand-binding domain. Consequently, the
      atomic displacement in the subunit interface around an intersubunit hydrogen bond
      was evoked in about 3 ps. This atomic displacement may perturb the subunit
      packing of the receptor, triggering receptor activation.

PMID- 14696184
TI  - Novel protein and Mg2+ configurations in the Mg2+GDP complex of the SRP GTPase
      ffh.
AB  - Ffh is the signal sequence recognition and targeting subunit of the prokaryotic
      signal recognition particle (SRP). Previous structural studies of the NG GTPase
      domain of Ffh demonstrated magnesium-dependent and magnesium-independent binding
      conformations for GDP and GMPPNP that are believed to reflect novel mechanisms
      for exchange and activation in this member of the GTPase superfamily. The current
      study of the NG GTPase bound to Mg(2+)GDP reveals two new binding conformations
      in the first the magnesium interactions are similar to those seen previously,
      however, the protein undergoes a conformational change that brings a conserved
      aspartate into its second coordination sphere. In the second, the protein
      conformation is similar to that seen previously, but the magnesium coordination
      sphere is disrupted so that only five oxygen ligands are present. The loss of the
      coordinating water molecule, at the position that would be occupied by the oxygen
      of the gamma-phosphate of GTP, is consistent with that position being privileged
      for exchange during phosphate release. The available structures of the GDP-bound
      protein provide a series of structural snapshots that illuminate steps along the
      pathway of GDP release following GTP hydrolysis.

PMID- 14696186
TI  - Free energies of binding of polychlorinated biphenyls to the estrogen receptor
      from a single simulation.
AB  - Relative free energies of binding to the ligand-binding domain of the estrogen
      receptor have been calculated for a series of 17 hydroxylated polychlorinated
      biphenyls. Because traditional thermodynamic integration or perturbation
      approaches are hardly feasible for these numbers of compounds, the one-step
      perturbation approach is applied and is shown to yield accurate results based on
      only two 2-ns molecular dynamics simulations of an unphysical, judiciously
      chosen, reference state. The mean absolute difference between the calculated and
      experimental binding free energies for the 17 compounds is 3.4 kJ/mol, which
      illustrates the accuracy of the GROMOS biomolecular force field used. Excluding
      the three largest ligands from the comparison reduces the deviation to 2.0 kJ/mol
      (i.e., < k(B)T). Apart from the relative free energy, structural information
      about the binding mode and binding orientation for every compound can also be
      extracted from the simulation, showing that a ligand bound to its receptor cannot
      be represented by a single conformation, but it samples an ensemble of different
      orientations.

PMID- 14696187
TI  - N-H...O, O-H...O, and C-H...O hydrogen bonds in protein-ligand complexes: strong
      and weak interactions in molecular recognition.
AB  - The characteristics of N-H...O, O-H...O, and C-H...O hydrogen bonds are examined
      in a group of 28 high-resolution crystal structures of protein-ligand complexes
      from the Protein Data Bank and compared with interactions found in small-molecule
      crystal structures from the Cambridge Structural Database. It is found that both
      strong and weak hydrogen bonds are involved in ligand binding. Because of the
      prevalence of multifurcation, the restrictive geometrical criteria set up for
      hydrogen bonds in small-molecule crystal structures may need to be relaxed in
      macromolecular structures. For example, there are definite deviations from
      linearity for the hydrogen bonds in protein-ligand complexes. The formation of C
      H...O hydrogen bonds is influenced by the activation of the C(alpha)-H atoms and
      by the flexibility of the side-chain atoms. In contrast to small-molecule
      structures, anticooperative geometries are common in the macromolecular
      structures studied here, and there is a gradual lengthening as the extent of
      furcation increases. C-H...O bonds formed by Gly, Phe, and Tyr residues are
      noteworthy. The numbers of hydrogen bond donors and acceptors agree with
      Lipinski's "rule of five" that predicts drug-like properties. Hydrogen bonds
      formed by water are also seen to be relevant in ligand binding. Ligand C-H...O(w)
      interactions are abundant when compared to N-H...O(w) and O-H...O(w). This
      suggests that ligands prefer to use their stronger hydrogen bond capabilities for
      use with the protein residues, leaving the weaker interactions to bind with
      water. In summary, the interplay between strong and weak interactions in ligand
      binding possibly leads to a satisfactory enthalpy-entropy balance. The
      implications of these results to crystallographic refinement and molecular
      dynamics software are discussed.

PMID- 14696188
TI  - Evaluation of protein fold comparison servers.
AB  - When a new protein structure has been determined, comparison with the database of
      known structures enables classification of its fold as new or belonging to a
      known class of proteins. This in turn may provide clues about the function of the
      protein. A large number of fold comparison programs have been developed, but they
      have never been subjected to a comprehensive and critical comparative analysis.
      Here we describe an evaluation of 11 publicly available, Web-based servers for
      automatic fold comparison. Both their functionality (e.g., user interface,
      presentation, and annotation of results) and their performance (i.e., how well
      established structural similarities are recognized) were assessed. The servers
      were subjected to a battery of performance tests covering a broad spectrum of
      folds as well as special cases, such as multidomain proteins, Calpha-only models,
      new folds, and NMR-based models. The CATH structural classification system was
      used as a reference. These tests revealed the strong and weak sides of each
      server. On the whole, CE, DALI, MATRAS, and VAST showed the best performance, but
      none of the servers achieved a 100% success rate. Where no structurally similar
      proteins are found by any individual server, it is recommended to try one or two
      other servers before any conclusions concerning the novelty of a fold are put on
      paper.

PMID- 14696189
TI  - Effective scoring function for protein sequence design.
AB  - We have developed an effective scoring function for protein design. The atomic
      solvation parameters, together with the weights of energy terms, were optimized
      so that residues corresponding to the native sequence were predicted with low
      energy in the training set of 28 protein structures. The solvation energy of non
      hydrogen-bonded hydrophilic atoms was considered separately and expressed in a
      nonlinear way. As a result, our scoring function predicted native residues as the
      most favorable in 59% of the total positions in 28 proteins. We then tested the
      scoring function by comparing the predicted stability changes for 103 T4 lysozyme
      mutants with the experimental values. The correlation coefficients were 0.77 for
      surface mutations and 0.71 for all mutations. Finally, the scoring function
      combined with Monte Carlo simulation was used to predict favorable sequences on a
      fixed backbone. The designed sequences were similar to the natural sequences of
      the family to which the template structure belonged. The profile of the designed
      sequences was helpful for identification of remote homologues of the native
      sequence.

PMID- 14696190
TI  - Strand-loop-strand motifs: prediction of hairpins and diverging turns in
      proteins.
AB  - Beta-sheet proteins have been particularly challenging for de novo structure
      prediction methods, which tend to pair adjacent beta-strands into beta-hairpins
      and produce overly local topologies. To remedy this problem and facilitate de
      novo prediction of beta-sheet protein structures, we have developed a neural
      network that classifies strand-loop-strand motifs by local hairpins and nonlocal
      diverging turns by using the amino acid sequence as input. The neural network is
      trained with a representative subset of the Protein Data Bank and achieves a
      prediction accuracy of 75.9 +/- 4.4% compared to a baseline prediction rate of
      59.1%. Hairpins are predicted with an accuracy of 77.3 +/- 6.1%, diverging turns
      with an accuracy of 73.9 +/- 6.0%. Incorporation of the beta-hairpin/diverging
      turn classification into the ROSETTA de novo structure prediction method led to
      higher contact order models and somewhat improved tertiary structure predictions
      for a test set of 11 all-beta-proteins and 3 alphabeta-proteins. The beta
      hairpin/diverging turn classification from amino acid sequences is available
      online for academic use (Meiler and Kuhn, 2003; www.jens
      meiler.de/turnpred.html).

PMID- 14696191
TI  - ProVal: a protein-scoring function for the selection of native and near-native
      folds.
AB  - A low-resolution scoring function for the selection of native and near-native
      structures from a set of predicted structures for a given protein sequence has
      been developed. The scoring function, ProVal (Protein Validate), used several
      variables that describe an aspect of protein structure for which the proximity to
      the native structure can be assessed quantitatively. Among the parameters
      included are a packing estimate, surface areas, and the contact order. A partial
      least squares for latent variables (PLS) model was built for each candidate set
      of the 28 decoy sets of structures generated for 22 different proteins using the
      described parameters as independent variables. The C(alpha) RMS of the candidate
      structures versus the experimental structure was used as the dependent variable.
      The final generalized scoring function was an average of all models derived,
      ensuring that the function was not optimized for specific fold classes or method
      of structure generation of the candidate folds. The results show that the crystal
      structure was scored best in 64% of the 28 test sets and was clearly separated
      from the decoys in many examples. In all the other cases in which the crystal
      structure did not rank first, it ranked within the top 10%. Thus, although ProVal
      could not distinguish between predicted structures that were similar overall in
      fold quality due to its inherently low resolution, it can clearly be used as a
      primary filter to eliminate approximately 90% of fold candidates generated by
      current prediction methods from all-atom modeling and further evaluation. The
      correlation between the predicted and actual C(alpha) RMS values varies
      considerably between the candidate fold sets.

PMID- 14696192
TI  - A new pairwise folding potential based on improved decoy generation and side
      chain packing.
AB  - A new force field for pairwise residue interactions as a function of C(alpha) to
      C(alpha) distances is presented. The force field was developed through the
      solution of a linear programming formulation with large sets of constraints. The
      constraints are based on the construction of >80,000 low-energy decoys for a set
      of proteins and requiring the decoy energies for each protein system to be higher
      than the native conformation of that particular protein. The generation of a
      robust force field was facilitated by the use of a novel decoy generation
      process, which involved the rational selection of proteins to add to the training
      set and included a significant energy minimization of the decoys. The force field
      was tested on a large set of decoys for various proteins not included in the
      training set and shown to perform well compared with a leading force field in
      identifying the native conformation for these proteins.

PMID- 14696193
TI  - Quantifying the effect of burial of amino acid residues on protein stability.
AB  - The average contribution of individual residue to folding stability and its
      dependence on buried accessible surface area (ASA) are obtained by two different
      approaches. One is based on experimental mutation data, and the other uses a new
      knowledge-based atom-atom potential of mean force. We show that the contribution
      of a residue has a significant correlation with buried ASA and the regression
      slopes of 20 amino acid residues (called the buriability) are all positive (pro
      burial). The buriability parameter provides a quantitative measure of the driving
      force for the burial of a residue. The large buriability gap observed between
      hydrophobic and hydrophilic residues is responsible for the burial of hydrophobic
      residues in soluble proteins. Possible factors that contribute to the buriability
      gap are discussed.

PMID- 14696194
TI  - Phenomenological similarities between protein denaturation and small-molecule
      dissolution: Insights into the mechanism driving the thermal resistance of
      globular proteins.
AB  - This article shows that the stability profiles of thermophilic proteins are
      significantly displaced toward higher temperatures as compared to those of
      mesophilic proteins. A similar trend characterizes the aqueous transfer of N
      alkyl amides. In fact, as a general feature of transfer processes, liquid
      dissolution profiles are centered at temperatures higher than those of solid
      ones. This behavior is governed by packing contributions. A partition of the
      unfolding thermodynamics based on the analysis of phenomenological temperatures
      common to dissolution and unfolding phenomena provides a clue to understanding
      the mechanism of thermal stabilization. In fact, the position of stability
      profiles along the temperature axis does not appear to depend on solvation of
      internal residues. Instead, it is notably affected by solidlike components, whose
      progressive decrease appears to drive the heat denaturation temperature increase
      of most thermostable proteins. As a corollary, it is shown that there are
      actually two limiting mechanisms of thermal stabilization.

PMID- 14696195
TI  - Class-specific correlations between protein folding rate, structure-derived, and
      sequence-derived descriptors.
AB  - Small single-domain proteins that fold by simple two-state kinetics have been
      shown to exhibit a wide variation in their folding rates. It has been proposed
      that folding mechanisms in these proteins are largely determined by the native
      state topology, and a significant correlation between folding rate and measures
      of the average topological complexity, such as relative contact order (RCO), has
      been reported. We perform a statistical analysis of folding rate and RCO in all
      three major structural classes (alpha, beta, and alpha/beta) of small two-state
      proteins and of RCO in groups of analogous and homologous small single-domain
      proteins with the same topology. We also study correlation between folding rate
      and the average physicochemical properties of amino acid sequences in two-state
      proteins. Our results indicate that 1) helical proteins have statistically
      distinguishable, class-specific folding rates; 2) RCO accounts for essentially
      all the variation of folding rate in helical proteins, but for only a part of the
      variation in beta-sheet-containing proteins; and 3) only a small fraction of the
      protein topologies studied show a topology-specific RCO. We also report a highly
      significant correlation between the folding rate and average intrinsic structural
      propensities of protein sequences. These results suggest that intrinsic
      structural propensities may be an important determinant of the rate of folding in
      small two-state proteins.

PMID- 14696196
TI  - Using evolutionary information for the query and target improves fold
      recognition.
AB  - In this study, we show that it is possible to increase the performance over PSI
      BLAST by using evolutionary information for both query and target sequences. This
      information can be used in three different ways: by sequence linking, profile
      profile alignments, and by combining sequence-profile and profile-sequence
      searches. If only PSI-BLAST is used, 16% of superfamily-related protein domains
      can be detected at 90% specificity, but if a sequence-profile and a profile
      sequence search are combined, this is increased to 20%, profile-profile searches
      detects 19%, whereas a linking procedure identifies 22% of these proteins. All
      three methods show equal performance, but the best combination of speed and
      accuracy seems to be obtained by the combined searches, because this method shows
      a good performance even at high specificity and the lowest computational cost. In
      addition, we show that the E-values reported by all these methods, including PSI
      BLAST, underestimate the true rate of false positives. This behavior is seen even
      if a very strict E-value cutoff and a limited number of iterations are used.
      However, the difference is more pronounced with a looser E-value cutoff and more
      iterations.

PMID- 14696197
TI  - A Shannon entropy-based filter detects high- quality profile-profile alignments
      in searches for remote homologues.
AB  - Detection of homologous proteins with low-sequence identity to a given target
      (remote homologues) is routinely performed with alignment algorithms that take
      advantage of sequence profile. In this article, we investigate the efficacy of
      different alignment procedures for the task at hand on a set of 185 protein pairs
      with similar structures but low-sequence similarity. Criteria based on the SCOP
      label detection and MaxSub scores are adopted to score the results. We
      investigate the efficacy of alignments based on sequence-sequence, sequence
      profile, and profile-profile information. We confirm that with profile-profile
      alignments the results are better than with other procedures. In addition, we
      report, and this is novel, that the selection of the results of the profile
      profile alignments can be improved by using Shannon entropy, indicating that this
      parameter is important to recognize good profile-profile alignments among a
      plethora of meaningless pairs. By this, we enhance the global search accuracy
      without losing sensitivity and filter out most of the erroneous alignments. We
      also show that when the entropy filtering is adopted, the quality of the
      resulting alignments is comparable to that computed for the target and template
      structures with CE, a structural alignment program.

PMID- 14696198
TI  - Evolutionary trace analysis of scorpion toxins specific for K-channels.
AB  - Scorpion alpha-K(+) channel toxins are a large family of polypeptides with a
      similar structure but diverse pharmacological activities. Despite many structural
      and functional data available at present, little progress has been made in
      understanding the toxin's molecular basis responsible for the functional
      diversification. In this paper, we report the first complete cDNA sequences of
      toxins belonging to subfamily 6 and identify five new members, called alpha-KTx
      6.6-6.10. By analyzing the rates of mutations that occurred in the corresponding
      cDNAs, we suggest that accelerated evolution in toxin-coding regions may be
      associated with the functional diversification of this subfamily. To pinpoint
      sites probably involved in the functional diversity of alpha-KTx family, we
      analyzed this family of sequences using the evolutionary trace method. This
      analysis highlighted one channel-binding surface common for all the members. This
      surface is composed of one conserved lysine residue at position 29 assisted by
      other residues at positions 10, 26, 27, 32, 34, and 36. Of them, the positions
      29, 32, and 34 have been reported to be the most major determinants of channel
      specificity. Interestingly, another contrary surface was also observed at a
      higher evolutionary time cut-off value, which may be involved in the binding of
      ERG (ether-a-go-go-related gene) channel-specific toxins. The good match between
      the trace residues and the functional epitopes of the toxins suggested that the
      evolutionary trace results reported here can be applied to predict channel
      binding sites of the toxins. Because, the side-chain variation in the trace
      positions is strongly linked with the functional alteration and channel-binding
      surface transfer of alpha-KTx family, we conclude that our findings should also
      be important for the rational design of new toxins targeting a given potassium
      channel with high selectivity.

PMID- 14696199
TI  - Crystal structure of the Escherichia coli YjiA protein suggests a GTP-dependent
      regulatory function.

PMID- 14696200
TI  - Chemical cross-linking and mass spectrometry for mapping three-dimensional
      structures of proteins and protein complexes.
AB  - Chemical cross-linking of proteins, an established method in protein chemistry,
      has gained renewed interest in combination with mass spectrometric analysis of
      the reaction products for elucidating low-resolution three-dimensional protein
      structures and interacting sequences in protein complexes. The identification of
      the large number of cross-linking sites from the complex mixtures generated by
      chemical cross-linking, however, remains a challenging task. This review
      describes the most popular cross-linking reagents for protein structure analysis
      and gives an overview of the strategies employing intra- or intermolecular
      chemical cross-linking and mass spectrometry. The various approaches described in
      the literature to facilitate detection of cross-linking products and also
      computer software for data analysis are reviewed. Cross-linking techniques
      combined with mass spectrometry and bioinformatic methods have the potential to
      provide the basis for an efficient structural characterization of proteins and
      protein complexes.

PMID- 14696202
TI  - Structural elucidation of natural 2-hydroxy di- and tricarboxylic acids and
      esters, phenylpropanoid esters and a flavonoid from Autonoe madeirensis using gas
      chromatographic/electron ionization, electrospray ionization and tandem mass
      spectrometric techniques.
AB  - The chemical composition of Autonoe madeirensis bulbs was characterized as part
      of a systematic phytochemical study of this species. The compounds reported were
      mainly identified on the basis of gas chromatography/electron ionization,
      electrospray ionization and tandem mass spectrometry. The structures of the pure
      compounds were also characterized by means of other physical and spectroscopic
      data (m.p., IR, UV, NMR). The compounds identified were 2-hydroxy di- and
      tricarboxylic acids and esters (malic acid, citric acid and their methyl and
      ethyl esters), cis- and trans-hydroxycinnamic esters (methyl and ethyl p
      coumarate and methyl ferulate) and a new flavone diglucoside, 7-O-[beta-glucosyl
      (1-->2)-O-beta-glucosyl]apigenin, the interglucosidic linkage (1-->2) of which
      is, to the best of our knowledge, reported for the first time in a diglucoside of
      apigenin. The results may contribute to the chemotaxonomy of the Autonoe genus
      and lead to a rapid tool for the systematic characterization of these compounds
      in plant extracts.

PMID- 14696203
TI  - Formation of solvated ions in the atmospheric interface of an electrospray
      ionization triple-quadrupole mass spectrometer.
AB  - A simple method capable of generating and investigating various solvent clusters
      and solvated ions was developed. The technique opens a door to studying these
      complexes on commercially available instruments. Formation of the desired
      solvated ion in the gas phase was achieved by introducing the appropriate
      volatile solvent vapour into the curtain gas stream. Capabilities of the
      technique are illustrated by generating alkali, alkaline earth and transition
      metal cations solvated by various volatile compounds such as water, methanol and
      acetonitrile. Depending on the ligands and on the experimental conditions,
      clusters of 2-100 molecules may be observed. Isotope labelling suggests that
      these are formed by a re-solvation process in the curtain gas region.

PMID- 14696204
TI  - Identification of anthraquinone coloring matters in natural red dyes by
      electrospray mass spectrometry coupled to capillary electrophoresis.
AB  - Capillary electrophoresis with UV/visible diode-array detection (DAD) and
      electrospray mass spectrometric (ESI-MS) detection were used for the
      identification of anthraquinone color components of cochineal, lac-dye and
      madder, natural red dyestuffs often used by ancient painters. For the purpose of
      such analysis, ESI-MS was found to be a much more appropriate detection technique
      than DAD one owing to its higher sensitivity (detection limits in the range 0.1
      0.5 micro g ml(-1)) and selectivity. The method developed made it possible to
      identify unequivocally carminic acid and laccaic acids A, B and E as coloring
      matters in the examined preparations of cochineal and lac-dye, respectively. In
      madder, European Rubia tinctorum, alizarin and purpurin were found. The method
      allows the rapid, direct and straightforward identification and quantification of
      components of natural products used in art and could be very helpful in
      restoration and conservation procedures.

PMID- 14696205
TI  - Two-dimensional microfabricated sources for nanoelectrospray.
AB  - The idea of a novel two-dimensional (2D) nanoelectrospray ionization emitter tip
      with the shape of a nib is explored here. This novel planar design is studied as
      an alternative to the needle-like standard emitter tips that suffer from a lack
      of reproducibility and robustness and from an inherent incompatibility with high
      throughput analysis. The composition of the micro-nib sources is analogous to the
      working of a simple fountain pen, with a liquid reservoir linked to a micro-nib
      tip from which the sample is electrosprayed via a capillary slot. The micro-nib
      prototypes described here were fabricated using microtechnology techniques and
      using the epoxy-based negative photoresist SU-8. The resulting free-standing
      micro-nib structure was supported by a silicon wafer. We present here two series
      of such micro-nib sources, the latter series exhibiting improved characteristics
      such as a 8 micro m source width of the nib tip. They were tested in mass
      spectrometry experiments on an ion trap mass spectrometer (LCQ Deca XP+, Thermo
      Finnigan) using standard peptide samples having concentrations down to 1 micro M
      and with a high voltage (HV) supply around 1 kV for the second series of micro
      nib sources. In addition to the stability of the spray, the obtained mass spectra
      showed the reliability of these sources for peptide analysis; the signal of the
      spectra was as intense and the signal-to-noise ratio (S/N) as high as that
      obtained with the use of standard emitter tips.

PMID- 14696206
TI  - Electrospray mass spectrometric investigation of the influence of the nature of
      mobile phase on the ionization of gallium and zirconium porphyrins.

PMID- 14696207
TI  - Improvement of quality of peptide mass spectra in matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry and post-source decay
      analysis of salty protein digests by using on-target washing.

PMID- 14696208
TI  - Miniature time-of-flight mass spectrometers.

PMID- 14696209
TI  - Liquid chromatographic/electrospray ionization mass spectrometric studies of
      proanthocyanidins in foods.
AB  - The proanthocyanidins in three foods (pinto beans, plums and cinnamon) were
      studied with electrospray ionization (ESI) mass spectrometry (MS) in the negative
      mode following separation by normal-phase high-performance liquid chromatography.
      The MS/MS analysis demonstrated that the major ions derived from heterocyclic
      ring fission and retro-Diels-Alder reaction of flavan-3-ol provided information
      about the hydroxylation pattern and type of interflavan bond. The connection
      sequence of the oligomers was identified through diagnostic ions derived from
      quinone methide (QM) cleavage of the interflavan bond. Novel heterogeneous B-type
      proanthocyanidins containing (epi)afzelechin as subunits were identified in pinto
      beans. Proanthocyanidins with interestingly different A-type linkages were
      identified in plums and cinnamon. In efforts aimed at extending the
      identification capacity of ESI-MS to polymers, we found that the polymeric
      procyanidins fragmented readily instead of forming multiply charged ions in the
      negative ESI mode. Fragmentation patterns were proposed based on our data
      obtained by ESI-MS/MS and ESI time-of-flight MS.

PMID- 14696210
TI  - Protein identification by peptide mass fingerprinting and peptide sequence
      tagging with alternating scans of nano-liquid chromatography/infrared multiphoton
      dissociation Fourier transform ion cyclotron resonance mass spectrometry.
AB  - We have developed a method for protein identification with peptide mass
      fingerprinting and sequence tagging using nano liquid chromatography (LC)/Fourier
      transform ion cyclotron resonance mass spectrometry (FTICR-MS). To achieve
      greater sensitivity, a nanoelectrospray (nano-ES) needle packed with reversed
      phase medium was used and connected to the nano-ES ion source of the FTICR mass
      spectrometer. To obtain peptide sequence tag information, infrared multiphoton
      dissociation (IRMPD) was carried out in nano-LC/FTICR-MS analysis. The analysis
      involves alternating nano-ES/FTICR-MS and nano-ES/IRMPD-FTICR-MS scans during a
      single LC run, which provides sets of parent and fragment ion masses of the
      proteolytic digest. The utility of this alternating-scan nano-LC/IRMPD-FTICR-MS
      approach was evaluated by using bovine serum albumin as a standard protein. We
      applied this approach to the protein identification of rat liver diacetyl
      reducing enzyme. It was demonstrated that this enzyme was correctly identified as
      3-alpha-hydroxysteroid dehydrogenase by the alternating-scan nano-LC/IRMPD-FTICR
      MS approach with accurate peptide mass fingerprinting and peptide sequence
      tagging.

PMID- 14696212
TI  - Current literature in mass spectrometry.

PMID- 14696211
TI  - Determination of the mandibular gland secretion of Polyergus rufescens queens by
      solid-phase microextraction and gas chromatography/mass spectrometry.

PMID- 14696213
TI  - MR safety.

PMID- 14696214
TI  - Clinical utility of the American College of Radiology MR Safe Practice
      Guidelines.

PMID- 14696215
TI  - Clinical applications of diffusion tensor imaging.
AB  - Directionally-ordered cellular structures that impede water motion, such as cell
      membranes and myelin, result in water mobility that is also directionally
      dependent. Diffusion tensor imaging characterizes this directional nature of
      water motion and thereby provides structural information that cannot be obtained
      by standard anatomic imaging. Quantitative apparent diffusion coefficients and
      fractional anisotropy have emerged from being primarily research tools to methods
      enabling valuable clinical applications. This review describes the clinical
      utility of diffusion tensor imaging, including the basic principles of the
      technique, acquisition, data analysis, and the major clinical applications.

PMID- 14696216
TI  - EPI-BOLD fMRI of human motor cortex at 1.5 T and 3.0 T: sensitivity dependence on
      echo time and acquisition bandwidth.
AB  - PURPOSE: To investigate the sensitivity dependence of BOLD functional imaging on
      MRI acquisition parameters in motor stimulation experiments using a finger
      tapping paradigm. MATERIALS AND METHODS: Gradient-echo echo-planar fMRI
      experiments were performed at 1.5 T and 3.0 T with varying acquisition echo time
      and bandwidth, and with a 4 mm isotropic voxel size. To analyze the BOLD
      sensitivity, the relative contributions of BOLD signal amplitude and thermal and
      physiologic noise sources were evaluated, and statistical t-scores were compared
      in the motor area. RESULTS: At 1.5 T, the number of activated pixels and the
      average t-score showed a relatively broad optimum over a TE range of 60-160 msec.
      At 3.0 T, an optimum range was observed between TEs of 30-130 msec. Averaged over
      nine subjects, maxima in the number of pixels and t-score values were 59% and 18%
      higher at 3.0 T than at 1.5 T, respectively, an improvement that was lower than
      the observed 100% to 110% increase in signal-to-noise ratio at 3.0 T. CONCLUSION:
      The somewhat disappointing increase in t-scores at 3.0 T was attributed to the
      increased contribution of physiologic noise at the higher field strength under
      the given experimental conditions. At both field strengths, reducing the
      effective image acquisition bandwidth from 35 to 17 Hz per pixel did not affect
      or only marginally affect the BOLD sensitivity.

PMID- 14696217
TI  - Asymmetry and gender effect in functionally lateralized cortical regions: a
      proton MRS imaging study.
AB  - PURPOSE: to compare metabolite concentrations and ratios in gray matter regions
      known for their anatomical/functional asymmetry and evaluate gender effect.
      MATERIALS AND METHODS: Proton MRS imaging was performed at 1.5 T with TR/TE
      2300/280 msec in 20 healthy right-handed subjects (mean age 29.6 +/- 5.3 years,
      10 men). Concentrations of N-acetyl aspartate (NAA), choline (Cho), and creatine
      (Cr), and the peak area ratios NAA/Cho, NAA/Cr, and Cho/Cr were evaluated in
      hippocampal and parahippocampal gyri, thalamus, insula, Broca's and Wernicke's
      areas (and corresponding contralateral areas), primary and secondary visual
      areas, temporal, inferior parietal, cingulate, supplemental motor, dorsolateral
      prefrontal, and sensorimotor areas. Linear mixed-effects regression models were
      used for statistical analyses. RESULTS: NAA concentration and NAA/Cho were higher
      in the left thalamus by 21.9% and 20%, respectively (both P < 0.001). NAA
      concentration was 13% higher in the region contralateral to Wernicke's area (P <
      0.02). No gender differences were found. CONCLUSION: Metabolite concentrations
      and ratios were symmetric and gender independent in most brain regions, however
      small hemispheric side differences in the thalamus and in Wernicke's area were
      found.

PMID- 14696218
TI  - Diffusion tensor imaging in the diagnosis of primary lateral sclerosis.
AB  - PURPOSE: To evaluate the utility of MR diffusion tensor imaging in diagnosing
      primary lateral sclerosis (PLS). MATERIALS AND METHODS: Five patients who met
      clinical criteria for a diagnosis of PLS, and two patients with possible PLS of
      less than three years duration and eight normal volunteers were studied using MR
      diffusion tensor imaging. RESULTS: All seven patients showed decreased diffusion
      anisotropy and increased diffusion constant in the PLIC, with complete separation
      from a normal control group, including patients early in the course of the
      illness. CONCLUSION: Quantitative diffusion tensor imaging appears to be a useful
      test to detect upper motor neuron damage and hence to help to establish the
      diagnosis of PLS.

PMID- 14696219
TI  - Comparison of spiral and FLASH phase velocity mapping, with and without breath
      holding, for the assessment of left and right coronary artery blood flow
      velocity.
AB  - PURPOSE: To develop high temporal resolution coronary artery spiral phase
      velocity mapping sequences and to compare the results obtained with those from
      FLASH sequences. MATERIALS AND METHODS: Velocity curves were obtained in eight
      left and eight right coronary arteries using breath-hold interleaved spiral
      (BH_SP), free-breathing interleaved spiral (FB_SP), breath-hold segmented FLASH
      (BH_FL), and free-breathing FLASH (FB_FL) sequences. Spatial resolution, temporal
      resolution, and acquisition durations (cardiac cycles) were as follows-BH_SP: 0.9
      mm x 0.9 mm, 30 msec, 20 cycles; FB_SP: 0.9 mm x 0.9 mm, 42 msec, 100 cycles;
      BH_FL: 0.9 mm x 1.8 mm, 70 msec (effective), 20 cycles; FB_FL: 0.9 mm x 1.8 mm,
      30 msec, 480 cycles. Peak systolic, peak diastolic, and mean velocities were
      compared between sequences. RESULTS: For left and right arteries, the FB_SP
      velocity profiles closely followed those from the FB_FL sequence. By comparison,
      the BH_FL sequence failed to resolve the sharp peaks in the temporal velocity
      profiles of the right coronary artery, significantly underestimating the peak
      systolic (88 mm/second vs. 252 mm/second, P < 0.001), peak diastolic (114
      mm/second vs. 153 mm/second, P < 0.01), and mean (56 mm/second vs. 93 mm/second,
      P < 0.001) velocities. For the less mobile left artery, the peak systolic, peak
      diastolic, and mean velocities were also underestimated by the BH_FL sequence,
      although this only reached statistical significance for the systolic peak (80
      mm/second vs. 135 mm/second, P < 0.01), 142 mm/second vs. 168 mm/second, (P =
      ns), and 87 mm/second vs. 101 mm/second, (P = ns) respectively. CONCLUSION: We
      have shown that the FB_SP sequence developed agrees well with the FB_FL sequence,
      while the study duration is reduced by a factor of 10 for the same spatial
      resolution. By comparison, the BH_FL sequence underestimates flow velocities,
      particularly in the more mobile right coronary artery.

PMID- 14696220
TI  - Mapping cyclic change of regional myocardial blood volume using steady-state
      susceptibility effect of iron oxide nanoparticles.
AB  - PURPOSE: To demonstrate an in vivo magnetic resonance imaging (MRI) technique
      that maps the cyclic change of regional myocardial blood volume (MBV) during the
      cardiac cycle. MATERIALS AND METHODS: The method is based on the dominant T(2)*
      shortening effect of iron oxide nanoparticle-induced magnetic susceptibility
      perturbation in myocardium in the steady state. The technique was demonstrated in
      vivo with normal mouse hearts at 9.4 T. The regional MBV maps in left ventricular
      myocardium were computed from the steady-state pre- and post-monocrystalline iron
      oxide nanoparticle (MION) gradient echo (GE) cine images. Cyclic changes of MBV
      in normal mice were analyzed quantitatively in different transmural and angular
      locations. RESULTS: High-resolution MBV maps at various cardiac points were
      obtained. The study showed a general regional MBV decrease from end-diastole (ED)
      to end-systole (ES). Percentage reductions were 18.2 +/- 6.6%, P < 0.03 in the
      lateral wall and 24.7 +/- 3.1%, P < 0.0002 in the interventricular septum. The
      heterogeneous characteristics of MBV transmural distribution were also reported.
      CONCLUSION: The steady-state susceptibility effect of intravascular
      superparamagnetic contrast agent (CA) can be used to map the cyclic change of
      regional MBV. This imaging approach is relatively simple and may provide a new
      perspective for functional assessment of the microvasculature in myocardium.

PMID- 14696221
TI  - Cine MR imaging of heart valve dysfunction with segmented true fast imaging with
      steady state free precession.
AB  - PURPOSE: To evaluate the value of cine true fast imaging with steady-state free
      precession (SSFP) for semiquantitative assessment of valvular dysfunction in the
      heart and to compare the results to that obtained with a standard breath-hold
      segmented gradient-recalled echo-planar imaging sequence (GE-EPI). MATERIALS AND
      METHODS: Twenty-three patients with known valvular dysfunction (main component:
      16 with aortic valve stenosis, nine with aortic valve insufficiency, three with
      mitral stenosis, two with mitral regurgitation, two with tricuspidal
      regurgitation, and one with pulmonary stenosis) and 23 control subjects with
      normal valvular function underwent MR imaging on a 1.5-T system (ACS-NT, Philips,
      Best, The Netherlands). Cine SSFP and GE-EPI images were acquired in identical
      long-axis views. Images were evaluated for the presence and extent of the signal
      void arising from the valves and for image quality consensus by two experienced
      radiologists. Results were compared to those obtained by cardiac catheterization
      (in 16 patients) or color Doppler (in the remaining seven patients). RESULTS: On
      SSPF images, the complex flow pattern in valvular regurgitant or stenotic lesions
      caused signal void within the bright blood pool of the atria or ventricles,
      similar to GE-EPI, in all patients. Valvular dysfunction was delineated using
      SSFP with the same high sensitivity (100%) as using the GE-EPI sequence. Results
      correlated to those obtained by cardiac catheterization or color Doppler
      ultrasonography (P < 0.001, r = 0.97). However, the jet phenomenon was slightly
      more pronounced in five patients on GE-EPI. There was no significant signal void
      in the 23 control subjects with both sequences. In all 46 subjects, the image
      quality of SSFP images was rated higher (P < 0.05; 2.6 +/- 0.1; using a scale
      ranging from 0-3) compared to GE-EPI (1.7 +/- 0.1). CONCLUSION: The results of
      this study suggest that valvular dysfunction can be semiquantitatively assessed
      using SSFP cine MR imaging.

PMID- 14696222
TI  - Proton magnetic resonance spectroscopic imaging of human breast cancer: a
      preliminary study.
AB  - PURPOSE: To investigate the diagnostic value of proton magnetic resonance
      spectroscopic imaging (MRSI) in patients with breast lesions. MATERIALS AND
      METHODS: Eighteen patients underwent breast MRSI and MRI at 1.5 T. Contrast
      enhanced MR was used to identify the lesion, after which single-slice MRSI (TR/TE
      = 2000/272 msec, 10-mm slice thickness) was performed. Water, lipid, and choline
      (Cho) images were reconstructed from MRSI data. The area of the Cho was measured
      in the lesion and expressed relative to the background noise level (signal-to
      noise ratio (SNR)), measured between 7.0 and 9.0 ppm. Cho SNRs were compared
      between benign and malignant lesions as determined by histopathology. RESULTS:
      Three cases were considered technical failures on MRSI. Of the remaining 15
      cases, on histopathology, eight were classified as malignant carcinoma and seven
      were benign. The Cho SNR from malignant tissue was significantly elevated
      compared to benign tissue (6.2 +/- 2.1 vs. 2.4 +/- 0.7, P < 0.0008). CONCLUSIONS:
      MRSI measurements of Cho are feasible in the human breast, and the SNR for Cho
      was significantly different between benign and malignant lesions. The potential
      advantages of MRSI over SV spectroscopy include the ability to assess multiple
      lesions as well as tissue with normal MRI appearance, as well as to perhaps gauge
      lesion borders and infiltration into surrounding tissue.

PMID- 14696223
TI  - Ferumoxide-enhanced MR imaging of hepatocellular carcinoma: correlation with
      histologic tumor grade and tumor vascularity.
AB  - PURPOSE: To evaluate ferumoxide-enhanced MR imaging findings of hepatocellular
      carcinomas (HCCs) in correlation with the histologic tumor grades and the tumor
      vascularity evaluated by CT hepatic arteriography (CTHA) and CT during arterial
      portography (CTAP) combined. MATERIALS AND METHODS: By searching the radiologic,
      surgical, and pathologic reports of our institution between January 1999 and
      February 2001, we identified 43 patients with 51 pathologically confirmed HCCs
      who underwent ferumoxide-enhanced MR imaging and combination CTHA and CTAP within
      two weeks. The HCCs consisted of 17 well-differentiated, 28 moderately
      differentiated, and six poorly differentiated tumors. The MR and CT were
      retrospectively reviewed by two radiologists in consensus for signal intensity on
      MR images and vascularity on CT. The Spearman's rank correlation coefficient was
      calculated to correlate the frequency of tumors with ferumoxide uptake with the
      histologic tumor grades and the tumor vascularity on CTHA and CTAP. RESULTS: A
      total of 45 tumors (88%) did not take up ferumoxide, and thus showed distinct,
      homogeneous hyperintensity. Six tumors (12%) ranging 5-16 mm in size (mean, 11
      mm) took up ferumoxide, and thus showed isointensity, mixed intensity, or
      hypointensity, including five of 17 (29%) well-differentiated tumors and one of
      28 (4%) moderately differentiated tumors. Five of the six tumors (83%) showed
      hyper- or hypovascularity on CTHA or hypovascularity on CTAP. The frequency of
      tumors with ferumoxide uptake showed weak correlation with tumor grades
      (coefficient = 0.26, P < 0.01) and vascularity on CTHA (-0.35, P < 0.05) and CTAP
      (0.39, P < 0.01). CONCLUSION: Although a small number of well-differentiated HCC
      take up ferumoxide and show iso-, mixed, or hypointensity, most such tumors show
      increased hepatic arterial or decreased portal venous perfusion. The present
      results suggest the limitation of reticuloendothelial contrast imaging,
      particularly in the diagnosis of small, well-differentiated HCC.

PMID- 14696224
TI  - Echo planar MR imaging of the liver: comparison of images with and without motion
      probing gradients.
AB  - PURPOSE: To determine whether MR images with motion-probing gradients (MPGs)
      usefully improve lesion detection in comparison with MR images without MPGs.
      MATERIALS AND METHODS: Echo planar (EP) images without MPGs and with small and
      intermediate MPGs (gradient factor b = 2, 18, and 188 second/mm(2), respectively)
      were acquired for 61 hepatic lesions (21 hepatocellular carcinomas (HCCs), 19
      metastases, eight hemangiomas, and 13 cysts). The lesion-to-liver signal
      intensity ratios (SIRs) of these lesions were calculated using EP images with and
      without MPGs. Qualitative analysis for detection of HCCs and metastases were also
      performed between the images without MPGs and with small MPGs. RESULTS: The SIRs
      of HCCs and metastases for the images with small MPGs were significantly higher
      than the values for the images without MPGs (P < 0.05), although no significant
      differences were found in the case of hemangiomas and cysts. In comparison to
      images without MPGs, images with small MPGs improved lesion detection of three
      metastases and six HCCs, and worsened lesion detection of two HCCs. CONCLUSION:
      Images with small MPGs may improve HCC and metastasis detection over images
      without MPGs.

PMID- 14696225
TI  - Assessment of anal fistulas with high-resolution subtraction MR-fistulography:
      comparison with surgical findings.
AB  - PURPOSE: To investigate a new MR-imaging protocol defined as subtraction MR
      fistulography for the detection of fistula-in-ano. MATERIALS AND METHODS: A total
      of 36 patients (18 men, 18 women) with the clinical diagnosis of anal fistula or
      abscess who were scheduled for surgical exploration were preoperatively imaged at
      1.5 T in the supine position; coronal STIR sequences and axial T1-weighted three
      dimensional FLASH sequences before and after intravenous injection of gadobenate
      dimeglumine (Gd-BOPTA) were obtained. Image subtraction was routinely used. The
      image findings were compared with the findings at surgical exploration according
      to a uniform classification system. RESULTS: A total of 46 fistulas were seen on
      subtraction MR-fistulography, whereas surgery described 41 fistulas. MRI and
      surgery concordantly depicted a total number of 40 fistulas, six fistulas were
      only described by MRI, and one fistula was only seen during surgery. A total of
      27 abscesses were detected with MRI, compared to 22 during surgery. A total of 22
      abscesses were concordantly diagnosed. Complete agreement between subtraction MR
      fistulography and surgery occurred in 32 (89%) of the 36 patients. The four
      patients in whom both procedures disagreed had complex anal sepsis with multiple
      fistulas and/or abscesses due to Crohn disease. CONCLUSION: High-resolution
      subtraction MR-fistulography is an important complement to surgical exploration
      and especially suitable for investigating complex anal sepsis.

PMID- 14696226
TI  - Magnetic resonance imaging of periosteum with ultrashort TE pulse sequences.
AB  - PURPOSE: To assess the values of pulse sequences with ultrashort echo times (0.08
      msec) for detecting and characterizing periosteum. MATERIALS AND METHODS: Two
      normal volunteers aged 33 and 58 years and 12 patients aged seven to 55 years
      were studied. A total of 10 of the patients had contrast enhancement with
      intravenous Gadodiamide. Two ovine tibias were examined before and after the
      periosteum was stripped from the bone. RESULTS: High signal regions were observed
      adjacent to cortical bone in all parts of the skeleton imaged. They were
      generally more conspicuous after fat suppression and contrast administration. In
      the ovine tibia there was a reduction in the high signal normally seen at the
      surface of the bone after periosteal stripping. The detached periosteum produced
      a high signal. Mean T(2)* values for adult human periosteum ranged from 5.3 to
      11.4 msec. After enhancement the signal intensity increased. In two patients with
      tibial fractures, increased periosteal signal was seen and this showed marked
      enhancement. Signals from periosteum could be simulated by fat, contrast-enhanced
      blood and artifacts. CONCLUSION: The periosteum can be visualized with ultrashort
      echo time pulse sequences in health and disease.

PMID- 14696227
TI  - Synovitis and soft tissue impingement of the ankle: assessment with enhanced
      three-dimensional FSPGR MR imaging.
AB  - PURPOSE: To assess soft tissue impingement as well as synovitis of the ankle
      associated with trauma by using contrast-enhanced (CE), fat-suppressed, three
      dimensional, fast gradient-recalled acquisition in the steady state with
      radiofrequency spoiling (FSPGR) magnetic resonance (MR) imaging. MATERIALS AND
      METHODS: A total of 36 patients who had had chronic ankle pain associated with a
      traumatic injury undertook fat-suppressed CE three-dimensional FSPGR MR imaging
      and then arthroscopy of the ankle. The ankle joint was divided into four
      compartments by anatomic details: the anterolateral gutter, anteromedial gutter,
      anterior recess, and posterior recess. Synovial enhancement was graded as
      follows: grade I, no enhancement; grade II, linear enhancement; grade III, focal
      nodular enhancement; and grade IV, irregular nodular enhancement. MR grading of
      the synovial enhancement (synovitis, grade III or IV; soft tissue impingement,
      grade III or IV with its intrusion from the capsular reflection) was compared
      with arthroscopic findings. A control study of twenty asymptomatic ankles was
      done for determining enhancement. Arthroscopy confirmed synovitis in 47
      compartments of 27 patients. Of the 27 patients, 15 revealed soft tissue
      impingement in 17 compartments. RESULTS: For the assessment of synovitis, fat
      suppressed CE three-dimensional FSPGR MR imaging had an accuracy of 72.9%,
      sensitivity of 91.5%, and specificity of 63.9%; whereas for that of soft tissue
      impingement it had an accuracy of 94.4%, sensitivity of 76.5%, and specificity of
      96.9%. All of the asymptomatic subjects showed grade I (81%) or II (19%) synovial
      enhancement. CONCLUSION: Fat-suppressed CE three-dimensional FSPGR MR imaging was
      sensitive for the evaluation of synovitis of the ankle associated with trauma,
      whereas it was specific for soft tissue impingement evaluation.

PMID- 14696228
TI  - Improved spectral selectivity and reduced susceptibility in SSFP using a near
      zero TE undersampled three-dimensional PR sequence.
AB  - PURPOSE: To improve the performance of fat/water separation and reduce the
      sensitivity to susceptibility variation in balanced SSFP sequences. MATERIALS AND
      METHODS: Decreasing the repetition time (TR) reduces susceptibility artifacts in
      SSFP imaging. A shorter TR may also improve the spectral selectivity obtained
      when linearly combining data acquired using different radiofrequency phase
      cycling schedules. The desired short TR is achieved by using an angularly
      undersampled three-dimensional radial acquisition sequence that achieves a near
      zero echo time (TE) and also a short TR. RESULTS: Images from human volunteers
      demonstrate broad coverage of the cervical spine and knee with isotropic
      resolution. Excellent fat/water separation is achieved in these studies.
      CONCLUSION: The short TR capability of the proposed sequence greatly improves the
      fat suppression in SSFP imaging. High-resolution volumetric T2-like contrast
      imaged with reduced susceptibility artifacts can be obtained from a single
      acquisition using this technique.

PMID- 14696229
TI  - Selective missing pulse steady state free precession (MP-SSFP): inner volume and
      chemical shift selective imaging in a steady state sequence.
AB  - PURPOSE: To examine new sequences that restrict acquisition of spins to those
      excited by both of the RF pulses in missing pulse steady state free precession
      (MP-SSFP) MRI. MATERIALS AND METHODS: New MP-SSFP sequences were created by
      replacing one of the slice selective pulses (SSPs) with an orthogonal SSP for
      inner volume imaging, and with a chemical shift selective (CHESS) pulse for
      chemical shift imaging. The inner volume sequence was applied to a reduced field
      of view at the center of a resolution phantom; resulting images were evaluated
      for differences in the aliased signal. The CHESS sequence was applied to
      volunteers, as well as to and fat, water, and acetic acid phantoms. Results were
      evaluated with SNR measurements. RESULTS: The inner volume sequence eliminated
      the aliased signal, while nonselected fat and water levels were suppressed to
      that of noise by the CHESS sequence. CONCLUSION: Results suggest a novel steady
      state technique for rapid inner volume or chemical shift imaging.

PMID- 14696230
TI  - Safety assessment of gadoversetamide (OptiMARK) administered by power injector.
AB  - PURPOSE: To evaluate the safety of OptiMARK (gadoversetamide injection)
      administered via power injector. MATERIALS AND METHODS: The study population
      included 144 healthy volunteers aged 18 years or older randomly assigned to one
      of seven treatment groups (N = 20/group). The safety assessment was based on
      changes in physical examination, vital signs, electrocardiograms (ECGs), standard
      clinical laboratory tests, and adverse events (AEs) through a 24-hour
      postinjection period. RESULTS: OptiMARK caused no serious AEs or unexpected
      changes in physical examinations or laboratory parameters. The changes observed
      in vital signs and ECG intervals did not vary with changes in injection rate and
      were not significantly (P < 0.05) different from those elicited by saline
      administration at the same rates. CONCLUSION: This study demonstrated the safety
      of OptiMARK when administered via a power injector at rates of 2, 4, and 6
      mL/second.

PMID- 14696231
TI  - Size "H" oxygen cylinder: accidental MR projectile at 1.5 Tesla.
AB  - The risks of ferromagnetic compressed gas cylinders becoming projectiles in an MR
      environment are well known (12). The recent death of a child from such an
      incident reinforces the potential for disaster (3).

PMID- 14696232
TI  - Effect of nitrogen application on flowering and yield of eggplant (Solanum
      melongena L.).
AB  - Effect of nitrogen application on number of flowers per plant, number of
      different types of flowers per plant, length of style, number of fruits per plant
      and fruit yield/ha of eggplant was investigated under controlled greenhouse
      conditions. Nitrogen was supplied at 50, 75, 100, 125, 150, 175 and 200 kg N/ha
      with one control (no nitrogen) treatment. Nitrogen supplied at 200 kg N/ha gave
      best results and significantly produced the highest number of flowers per plant,
      fruits per plant and yield (32.24 ton/ha) over control plants. Nitrogen failed to
      influence style length and type of flowers i.e. long, medium, pseudo-short and
      short styled flowers. Nitrogen application at 150 and 175 kg N/ha showed
      comparable results with nitrogen applied at 200 kg N/ha.

PMID- 14696233
TI  - Calibration and inverse modelling of soil physical and biological parameters of a
      nitrate leaching model with the pest programme.
AB  - This paper reports on experiences with the use of the PEST (Parameter ESTimation)
      programme to calibrate the soil physical parameters of a nitrate leaching model
      (the Burns alpha model) and to determine the N mineralization rate by inverse
      modelling. Parameter estimation was much more efficient and accurate with the
      PEST programme than with a built in "trial and error" calibration module. The
      determination of the N mineralization rate by inverse modelling with PEST using
      measured nitrate concentrations was not possible, and several reasons for this
      are given. With more suitable experimental fields (lighter soil texture and/or
      deeper groundwater level), more replications in the nitrate measurements and a
      one-step calibration of the alpha parameter and the N mineralization rate,
      determination of the N mineralization rate may become possible.

PMID- 14696234
TI  - Overview and quantification of the factors affecting the upstream and downstream
      movements of Gammarus pulex (Amphipoda).
AB  - Human activities have severely deteriorated the Flemish river systems, and many
      functions such as drinking water supply, fishing, ... are threatened. Because
      their restoration entails drastic social (e.g. change in habits with regard to
      water use and discharge, urban planning) and economical (e.g. investment in
      nature restoration, wastewater treatment system installation) consequences, the
      decisions should be taken with enough forethought. Ecosystem models can act as
      interesting tools to support decision-making in river restoration management. In
      particular models that can predict the habitat requirements of organisms are of
      considerable importance to ensure that the planned actions have the desired
      effects on the aquatic ecosystems. In preliminary studies, Artificial Neural
      Network (ANN) models were tested and optimized to obtain the best model
      configuration for the prediction of the habitat suitability for Gammarus pulex
      based on the abiotic characteristics of their aquatic environment in the Zwalm
      river basin (Flanders, Belgium). Although, these ANN models are in general quite
      robust with a rather high predictive reliability, the model performance has to be
      increased with regard to simulations for river restoration management. In
      particular, spatial-temporal expert-rules have to be included. Migration kinetics
      (downstream drift and upstream migration) of the organism and migration barriers
      along the river (weirs, impounded river sections, ...) can deliver important
      additional information on the effectiveness of the restoration plans, and also on
      the timing of the expected effects. This paper presents an overview and
      quantification of the factors affecting the upstream and downstream movements of
      Gammarus pulex. During further research, ANN models will be used to predict the
      habitat suitability for Gammarus pulex after several restoration options. The
      migration models, implemented in a Geographical Information System (GIS), are
      applied to calculate the migration time to the restored parts of the river. In
      this way, decision makers have an idea whether and when a selected restoration
      option has the desired effect.

PMID- 14696235
TI  - Evaluation of a synthetic wastewater with variable COD soluble/COD total and its
      use in a lab scale clarigester.

PMID- 14696236
TI  - In vitro effects of RH-0345 and KK-42 on ecdysteroid levels and cuticle synthesis
      by pupal integument of mealworms.
AB  - In this study, the effects of two insect growth regulators (KK-42 and RH-0345),
      applied either alone or in combination, were evaluated on the ecdysteroid
      production in vitro. Integument explants from the abdominal sternites of newly
      ecdysed pupae of mealworms, Tenebrio molitor, were cultured and the amounts of
      ecdysteroids, released into the culture medium, were determined by an enzyme
      immunoassay (EIA) after various intervals of incubation. In combined treatments,
      explants were cultured for the first two days in a medium added with the first
      compound and then transferred in new medium containing the second compound. EIA
      measurements showed that RH-0345, either alone or followed by KK-42, resulted in
      higher amounts of ecdysteroids as compared to controls. In contrast, KK-42 alone
      caused a significant reduction. But, when KK-42 was followed by RH-0345, the
      ecdysteroid amounts were equal to controls. In another series of experiments, the
      effects on cuticle secretion were examined. Only in the case that explants were
      treated with RH-0345, either alone or followed by KK-42, new cuticle synthesis
      was observed.

PMID- 14696237
TI  - Agricultural effects on yield and nutritive value of grassland under a limited
      fertilisation rate on sandy soils in Flanders.
AB  - From 1999 to 2002, we studied the yield production and quality parameters of
      grassland installed on sandy soils (1) under normal management (NM), (2) under
      management with respect to meadow birds (MBM) -first mowing date 15 June or later
      and (3) under botanical management (BM) -first mowing date 1 July or later. The
      experiments were conducted at two locations, Aalter and Geel. The biomass
      production under MBM and BM decreased by resp. 19% and 46% as compared to the NM.
      The nitrogen content in the vegetation of the delayed first cut (without
      fertilisation) of MBM (2.4%) and BM (2.3%) was much lower than under NM (3.3%).
      Since the first cut makes the major part of the total annual dry matter yield
      (43% for MBM and 59% for BM), the average nitrogen content of the overall DM
      yield dropped substantially if the first cut was delayed. The same phenomenon
      occurred for the digestibility of the organic matter: overall 66% for MBM and 59%
      for BM as compared to 69% for NM. The digestibility was partially influenced by
      the botanical composition. MBM resulted in a shift in botanical composition,
      favouring Poa trivialis L., Ranunculus repens L., and Holcus lanatus L. as
      compared to NM. BM mainly favoured Holcus lanatus L., and Ranunculus repens L. as
      compared to NM. Under the management types with delayed first cut, problems with
      residual mineral soil N never occurred.

PMID- 14696238
TI  - Patient safety alert. Pediatrics program just the beginning of safety overhaul.

PMID- 14696239
TI  - Data help case management demonstrate its contributions.

PMID- 14696241
TI  - Inpatient case managers handle discharges, review.

PMID- 14696240
TI  - Discharge planning system makes documenting easy.

PMID- 14696243
TI  - Computer documentation won't cure all problems.

PMID- 14696242
TI  - SSM slashes LOS almost two days in just two weeks.

PMID- 14696245
TI  - Hospitals seeking SNF beds think creatively.

PMID- 14696244
TI  - Do you offer a choice on home care services?

PMID- 14696246
TI  - Navigating the 'Bermuda Triangle' of ethics.

PMID- 14696247
TI  - Perspectives. Now what? Wonks weigh in on Rx bill's future.

PMID- 14696248
TI  - Transforming the revenue cycle through payer-provider collaboration.

PMID- 14696249
TI  - Billing and coding update.

PMID- 14696250
TI  - [Study of DNA-containing structures in the nucleus and cytoplasm of the Crithidia
      flagellates using the Miller method].
AB  - Weakly condensed interphase chromosomes made of chromatin, and the tightly packed
      kinetoplast DNA (kpDNA) of a single mitochondrion of Crithidia (Kinetoplastidea,
      Trypanosomatida) flagellates were studied on the Miller-type spread preparations
      by electron microscopy. Chromatin of organisms lysed at low ionic strength
      conditions for 5-10 min unfolds up to 10-nm nucleosomal filaments and 20-nm
      chromatin fibers. The initial indications of kpDNA decompaction become visible
      after a 10-13 min dispersion of lysed flagellates. However, at least a 15 min
      long procedure is required for well-defined identification of intrakinetoplast
      structures. In this case, the kinetoplast looks like a heterogeneous network
      disposed close to the kinetosome of a single flagellum. Cells with diameters of
      162.5 nm and contour wall length of 510 nm dominated within the network. With the
      prolongation of the dispersion time up to 20 min both these parameters increased
      up to 218 and 686 nm, respectively. Further prolongation of the treatment up to
      60 min results in wall disruption in many cells. Within these cells, some
      isolated circular kpDNA molecules appear with the contour length of 588-792 nm.
      The circles of this size correspond to individual minicircles of the Crithidia
      kpDNA. Partly unfolded maxicircles of the kpDNA can be found only at early stages
      of dispersion (10 min). Special features of compaction of DNA-containing
      structures in both the nucleus and cytoplasm of Crithidia are discussed.

PMID- 14696252
TI  - [Evolutionary regularities of the somatic polyploidy manifestation in salivary
      glands of gastropod molluscs. IV. A subclass of Pectinibranchia: Orders
      Hamiglossa and Toxoglossa (Neogastropoda)].
AB  - Salivary glands of 12 species of carnivorous gastropod molluscs, making the
      Neogastropoda group have been investigated by histochemical methods and DNA
      cytophotometry. We studied the anatomical and histological structure of ordinary
      (acinous) and accessory (tubular) salivary glands, and of unpaired glands
      (Leiblen's, "framboisee", and poisonous). Cells of three types were
      distinguished: granular cells (with glycoproteid granular inclusions), mucocytes
      I (with sulfatic acid mucopolysaccharides), and epithelial ciliated cells. In
      ordinary and accessory glands of the studied Neogastropods, polyploid cells with
      polyploidy levels from 4c to 16c were revealed together with diploid cells. The
      functional significance and phylogenetic tendencies of polyploidy manifestation
      in salivary glands of prosobranch gastropods are discussed.

PMID- 14696251
TI  - [Position of the satellite DNA relative to heterochromatin in the interphase
      nuclei in cultured cells].
AB  - It is considered that centromeric (CEN) regions play the leading role in the
      formation of chromocentres predominantly consisting of satellite DNA. Cloned
      mouse and human satellite DNA sequences from CEN and periGEN regions were used in
      order to trace their positions relative to chromocentres. Methods of fluorescent
      in situ hybridization (FISH) and immunoFISH with antibodies against CENP-B, known
      is a marker of prekinetochore, were employed. Peripheral position of the signals
      was observed at the chromocentres, but a combined signal of GEN and periGEN
      satellite DNAs never covered the whole brightly DAPI stained regions. A
      reasonable amount of the chromocentre body is not a satellite DNA. We suppose
      that the matrix-associated regions (MAR) of structural genes and, probably, the
      heavy methylated coding sequences of the genes, which are not expressed in the
      given cell type, are included in the chromocentres in addition to satellite DNAs.

PMID- 14696253
TI  - [Anti-apoptotic and antiproliferative effect of bcl-2 gene transferred to E1A+cHa
      ras-transformed cells].
AB  - Transformed rat embryo fibroblasts E1A + cHa-ras known to possess high
      proapoptotic sensitivity and not to be arrested after DNA damage or upon serum
      starvation, were transfected with bcl-2 gene using calcium-phosphate
      precipitation method. Triple transformants E1A + cHa-ras + bcl-2 appeared to be
      protected from damage- and serum depletion-induced apoptosis and to restore cell
      cycle checkpoint control. Using the method of flow cytometry we have shown that
      these transformants are arrested in different phases of cell cycle in response to
      irradiation, adriamycin treatment and serum deprivation. Overexpression of bcl-2
      in E1A + cHa-ras-transformed cells entirely suppresses adriamycin-induced
      apoptosis and significantly reduces the level of apoptosis triggered by
      irradiation and growth factor withdrawal, as we have revealed by the test of
      clonogenic survival and electrophoretic analysis of oligonucleosomal DNA
      fragmentation. Our results have demonstrated, for the first time, that the
      oncogenic Ras co-immunoprecipitates with transfected Bcl-2 in E1A + cHa-ras + bcl
      2 transformed cells after irradiation but not after adriamycin treatment. Bcl-2
      Ras complexes were also observed in transformants E1A + cHa-ras + bcl-2 after
      serum starvation. Taken together, these data suggest that Bcl-2 and Ras
      interaction might play a crucial role in the cell cycle checkpoints restoration
      and apoptotic events regulation in transformants E1A + cHa-ras + bcl-2 exposed to
      DNA-damaging factors or growth factor-deprived.

PMID- 14696254
TI  - [Mechanism of thermoresistance in Escherichia coli cells exposed to temperature
      elevation].
AB  - The influence of media with different osmotic pressure (NaCl water solution) and
      chloramphenicol (10 micrograms/ml) on the survival, permeability, and survival
      curve shape of Escherichia coli B/r and E. coli Bs-1 cells, heated up to 50, 52,
      and 60 degrees C was investigated. As shown, the survival curve of cells heated
      up to 60 degrees C in isotonic conditions was characterized by exponential shape,
      while the survival curves of cells heated up to 50 and 52 degrees C consisted of
      two components characterizing thermosensitive and thermoresistant parts of cell
      population. Hypertonic conditions of heat at 52 degrees C decreased cell
      lethality and permeability. In this case, survival curves were characterized by
      exponential shape. Chloramphenicol was shown to protect against damaging action
      of heat at 50 degrees C and not to affect the viability of cells heated at 52 and
      60 degrees C. It is proposed that the increase of cell thermoresistance with heat
      dose elevation at 50 and 52 degrees C in isotonic conditions, which is
      accompanied by the appearance of thermotolerant components on survival curves,
      may be associated with accommodational cell reactions. The essence of these
      reactions consists in stabilization of the osmotic cell homeostasis.

PMID- 14696255
TI  - [Delivery of "suicide" thymidine kinase gene of herpes virus in the complex with
      cationic peptide into human hepatoma cells in vitro].
AB  - The delivery of "suicide" herpes simplex virus type-1 thymidine kinase gene (tk)
      into tumor cells, followed by treatment with synthetic nucleotide analogues
      (gancyclovir, acyclovir), is a perspective approach to cancer therapy. Serious
      limitations in employment of the existing means of gene delivery into target
      cells constitute the main obstacle for cancer gene therapy development. In the
      present work a possibility to use a nonviral gene delivery system is shown based
      on the employment of lysine rich peptide K8 and amphipathic peptide JTS-1 for
      transferring tk gene into human hepatoma HepG2 cells. Cationic peptide K8 forms
      compact complexes with plasmid DNA, and JTS-1 acts as a pH-dependent endosomal
      releasing agent. Transfection of HepG2 cells by tk expression vector coupled with
      K8/JTS-1 peptides, followed by acyclovir administration (50-100 micrograms/ml)
      for 24 h leads to cell cycle arrest in the G1/S checkpoint of some cells, which
      eventually die through apoptosis. Treatment of HepG2 cells with higher acyclovir
      concentration (200 micrograms/ml) additionally results in a nonspecific toxic
      effect. The above results demonstrate the efficacy of K8/JTS-1 delivery system
      for the "suicide" cancer gene therapy, and may be regarded as a basis for further
      elaboration of "suicide" cancer approaches in vivo.

PMID- 14696256
TI  - [Stimulation of DNA repair in human cells damaged by UV and ionizing radiation
      with soluble growth factors of photomodified blood].
AB  - Exposure of a small skin area of volunteers to UV light in 1 minimal erythemal
      dose is accompanied by rapid appearance in the circulating blood of soluble
      factors able to restore proliferation of X-ray-damaged autologous lymphocytes, to
      decrease frequency of chromosome breaks, and to stimulate unscheduled DNA
      synthesis. The appearance of such an activity in the blood can be also induced
      without skin irradiation. For this, one volume of a directly UV-irradiated blood
      is to be mixed in vitro with 10-fold volumes of intact blood, thus modeling the
      in vivo situation, when a small amount of transcutaneously UV-irradiated blood
      mixes with intact blood in the circulation. It has been found that the platelet
      derived growth factor and epidermal growth factor, added at physiological
      concentrations to the culture medium, decrease chromosome break frequency in X
      damaged cells.

PMID- 14696257
TI  - [Evaluation criterion for nuclear chromatin state of human spermatozoa using flow
      cytometry--a fertility test].
AB  - On the basis of the previously described method for estimating the state of the
      human spermatozoan nuclear chromatin by flow cytometry, we developed a modified
      system of calculation and presentation of our data. We propose a criterion that
      allows to classify samples of seminal material according to their fertility
      potential that could be used for male sterility diagnostics and as a prognostic
      test for optimization of reproduction programs. The most important theoretical
      and methodical aspects of the suggested approach are discussed, and comparative
      analysis of suggested approach and routine flow cytometry SCSA method is made.

PMID- 14696258
TI  - [Ultrastructure of the flagellate Cruzella marina (Kinetoplastidea)].
AB  - The ultrastructure of a marine, free-living heterotrophic kinetoplastid Cruzella
      marina was investigated with special attention being paid to the mitochondrion
      and flagellar organization. The flagellates have a polykinetoplastidal
      mitochondrion. Two flagella emerge from the pocket; one of these turns anteriorly
      being forward-directed, while the other is posteriorly directed to be adjacent to
      the ventral cell surface. The transition zone of both the flagella includes
      central filaments. The cytostome opens on the tip of the rostrum. The cytostome
      leads to the channel of cytopharynx, which penetrates the rostrum and proceeds
      into the flagellate body cytoplasm. The comparison of the relevant morphological
      and molecular data suggest that C. marina may arise early in the Kinetoplastidea
      lineage, before divergence of the majority taxa of the kinetoplastid flagellates.

PMID- 14696259
TI  - [Effect of modification of cell calcium status on lectin activity].
AB  - Effects of oryzalin (10 microM), an inhibitor of microtubule polymerization, on
      the activity of soluble and cell wall lectins were studied in 7 day-old seedlings
      of unhardened (23 degrees C) and cold acclimated (7 days at 2-3 degrees C) winter
      wheat (Triticum aestivum L.). Seedlings were grown in the presence of 25 microM
      and 1 mM Ca2+, 500 microM verapamil, 250 microM chlorpromazine or without
      modifiers of calcium status in the medium. Inhibitor of the microtubule
      polymerization inhibitor, likely as inhibitors of Ca(2+)-signal, decreased the
      activity of soluble lectins and increased that of cell wall lectins. Apparently,
      injury of microtubule phosphorylation results in a more considerable microtubule
      disorganization, than that observed after oryzalin effect. A low Ca2+
      concentration (25 microM) depressed, while a high concentration (1 mM) prompted
      microtubule sensibility to oryzalin. Such an effect of high Ca2+ concentration
      may be related to destabilizative action of Ca(2+)-calmodulin in these
      conditions, because chlorpromazine decreased oryzalin-induced increase in the
      activity of cell wall lectins with 1 mM Ca2+. It is concluded that the activity
      of cell wall lectins depends on the microtubule status that is regulated by
      calcium signal.

PMID- 14696261
TI  - [Radioadaptive enhancement of the repair of UV-induced postreplication gaps in
      Escherichia coli cells deficient in DNA repair].
AB  - In UV-irradiated E. coli WP2 uvrA, deficient in excision repair of DNA with
      pyrimidine dimers, gamma-irradiation in low doses (radioadaptation) before UV
      irradiation leads to the intensification of postreplication repair of DNA. This
      process in WP2 uvrA polA and uvrA lexA mutants is less than in WP2 uvrA cells,
      but in WP2 uvrA recA both postreplication repair and its radioadaptive
      intensification are absent. In E. coli AB1157 excising pyrimidine dimers the
      radioadaptive intensification of postreplication repair of DNA is expressed
      almost to the same extent as in WP2 uvrA. In GW2100 umuC mutant, deficient in DNA
      polymerase V, postreplication repair of DNA is expressed, but its radioadaptive
      intensification is absent, while in AB2463 recA13 both postreplication repair of
      DNA and radioadaptive intensification of postreplication repair of DNA are
      absent. The above data suggest that DNA polymerase I and LexA protein are needed
      for radioadaptive intensification of postreplication repair of DNA in uvrA
      strain, and DNA polymerase V is needed for radioadaptive intensification in E.
      coli AB1157, and that RecA protein is required for postreplication repair and
      radioadaptive intensification of postreplication repair of DNA.

PMID- 14696260
TI  - [Effect of laminin on karyotypic variability in cell line of Indian muntjac skin
      fibroblasts].
AB  - The numerical and structural karyotypic variability has been investigated in the
      Indian muntjac skin fibroblasts cell line M and karyotypic variant of this line
      M' on cultivation on a laminin 2/4 coated surface. In cell line M, cultivated on
      the laminin-coated surface for 4 and 14 days, and in karyotypic variant M',
      cultivated for 2, 4 and 14 days, the character of cell distribution for the
      chromosome number has changed. These changes involve a significant decrease in
      frequency of cells with model numbers of chromosomes, and an increase in
      frequency of cells with lower chromosome numbers. As a result, new modal
      chromosome numbers form. The frequency of cells with 4 chromosomes increases
      significantly; as a rule, such cells are absent in the control cell variants.
      Many new additional structural variants of the karyotype (SVK) appear. Detachment
      of cells M' from the laminin-coated surface followed by a 2 day cultivation on a
      hydrophilic surface, commonly used for routine cell cultivation, does not restore
      the control cell distribution for chromosomal number. The frequency of
      chromosomal aberrations on cultivation of the laminin-coated surface does not
      change relatively to controls. The observed alterations seem to be due to both
      disturbances of mitotic apparatus and selection of SVK, which are more
      advantageous to changed culture conditions of the cell population.

PMID- 14696262
TI  - The UNI/CARE perspective. Software implementation consortiums: a cost saving
      opportunity.

PMID- 14696263
TI  - Accountability requirements for reimbursement. Is the trend successful?

PMID- 14696264
TI  - Behavioral healthcare finance in a technology environment.

PMID- 14696265
TI  - How changes in reimbursement have affected the state of Georgia.

PMID- 14696266
TI  - North Carolina public mental health reform: impact on reimbursement resources.

PMID- 14696267
TI  - The state wants what? Integrated payment and reporting system in North Carolina.

PMID- 14696268
TI  - Reimbursement challenges in the state of Indiana.

PMID- 14696269
TI  - Bioethics and human rights.

PMID- 14696270
TI  - Clinical equipoise and the therapeutic misconception.

PMID- 14696271
TI  - Clinical equipoise and the therapeutic misconception.

PMID- 14696272
TI  - Clinical equipoise and the therapeutic misconception.

PMID- 14696273
TI  - Compulsory medical treatment: the limits of bodily integrity.

PMID- 14696274
TI  - The abuse of alternative medicine?

PMID- 14696275
TI  - Bioethics as if relationships matter.

PMID- 14696276
TI  - Threats to the common good. Biochemical weapons and human subjects research.

PMID- 14696277
TI  - The smallpox vaccination of health care workers: professional obligations and
      defense against bioterrorism.

PMID- 14696278
TI  - Biotech & justice. Catching up with the real world order.

PMID- 14696279
TI  - Promoting patient safety. An ethical basis for policy deliberation.

PMID- 14696280
TI  - What's a hospitalist?

PMID- 14696281
TI  - Pediatric hospitalists.

PMID- 14696282
TI  - A 6-year-old with a complex medical history and recurrent strokes.

PMID- 14696283
TI  - Community pediatricians collaborate with hospitalists to build a ward service.
AB  - Variations in hospitalist models carry advantages and disadvantages, many of
      which can be elucidated through the guidance of an experienced consultant or
      director. Implementation presents several challenges. Although there are common
      themes among various types of hospitalist programs, the specific activities of
      the team must be carefully tailored to the needs of the ward. The ideal would be
      to dovetail the hospitalist's activities with those of other services in the
      hospital, according to the preferences and expressed needs of the medical staff
      and hospital administration. This is an ambitious and elusive goal. One common
      thread is that the choice of hospitalist service requires considerable input from
      the community physicians in order to ensure success of the program. Program
      directors, hospital administrators, and medical staff organizations are strongly
      encouraged to seek the pediatricians' input early in the planning stages and
      throughout the course of design and implementation. In the end, a hospitalist
      program may serve to raise the level of care on the ward, support the needs of
      community pediatricians, and bring a new level of efficiency, consistency, and
      specialization to the care of the community's children.

PMID- 14696284
TI  - Managing a pediatric hospitalist practice requires team approach.
AB  - Establishing and maintaining a productive hospitalist program relies on the
      forging of multiple partnerships involving pediatric hospitalists, community
      practitioners, and administrative organizations including hospitals and multiple
      practice groups. When these professional relationships are successful, everyone
      in the relationship benefits, especially the children and families who deserve
      the best medical practices that can be offered. Establishing these relationships
      within defined communities ultimately improves pediatric outcomes.

PMID- 14696285
TI  - Pediatric hospitalists fill varied roles in the care of newborns.
AB  - The use of hospitalists in the care of newborns appears to be increasing and may
      be advantageous for several reasons, including decreased cost, decreased length
      of stay, increased patient survival, increased availability, and greater
      experience among hospitalists. Research specific to the use of hospitalists in
      newborn medicine needs to be done to support this hypothesis. Non-clinical
      activities such as teaching, developing clinical guidelines, and taking an active
      role in hospital and academic leadership also may improve education and patient
      care. It is essential that hospitalists who provide care in nurseries work to
      smooth the transition to a PCP and not act as a barrier. Relatively speaking, the
      care provided by hospitalists is most often short-term, and the relationship
      between infants and their parents with the PCP should begin as soon as possible.

PMID- 14696286
TI  - Integrating hospitalists into the pediatric intensive care unit.
AB  - The role of the pediatric hospitalist has an extremely bright future in many
      facets of the pediatric healthcare spectrum. The role of the hospitalist in the
      PICU is only one of many that shows great promise and will likely change our
      current models of care for children. The greatest challenge will be the education
      of healthcare providers who may see these changes as erosion in care, rather than
      as an important asset in providing quality care for children.

PMID- 14696287
TI  - How pediatric hospitalist programs can affect graduate medical education.

PMID- 14696288
TI  - Eating disorders and substance use: be aware of this dual diagnosis.
AB  - In summary, dual-diagnosis patients are challenging; their symptoms interact and
      may lead to dangerous medical sequelae. Their addiction and addiction-like
      behaviors are therefore best addressed in settings equipped to offer a parallel
      and simultaneous treatment course for both ED and SUD.

PMID- 14696289
TI  - Medication developments in the treatment of mental illness.

PMID- 14696290
TI  - A court case that could galvanize a field. Raytheon v. Hernandez.

PMID- 14696291
TI  - A focus on overall wellness: new hope for the seriously ill. Pharmaceutical
      academic partnership moves well beyond symptom reduction.

PMID- 14696292
TI  - No time for time management? Behavioral agencies have several options for
      improving staff efficiency.

PMID- 14696293
TI  - Standardization in behavioral health and its impact on software systems.

PMID- 14696294
TI  - Technology vendors, provider group seek productive partnership.

PMID- 14696295
TI  - Technology pioneer foresees closer relationships with end users.

PMID- 14696296
TI  - Esophageal emergencies: things that will wake you from a sound sleep.
AB  - Esophageal emergencies are a common problem facing practicing gastroenterologists
      and it is important to know what therapies are indicated for different
      situations. Patients ingesting caustic agents should be monitored intensively for
      signs of perforation and ultimately for signs of stricture development. Foreign
      bodies impacted in the esophagus should be removed promptly to prevent
      perforation. Although esophageal perforations are generally managed surgically,
      conservative management of localized perforations has become more common
      especially with improved antibiotics and the use of nonsurgical interventional
      drainage techniques. In either elected course the gastroenterologist should work
      closely with the surgical team.

PMID- 14696297
TI  - Nonvariceal upper gastrointestinal bleeding.
AB  - Nonvariceal UGI bleeding is one of the most common emergencies that
      gastroenterologists encounter, and continues to be a significant cause of
      morbidity and mortality. The keys to management are rapid resuscitation and
      stabilization; appropriate triage based on pre-endoscopic risk factors; early
      endoscopy to achieve prompt diagnosis and implement hemostatic therapy to high
      risk lesions; and aggressive antisecretory therapy (in the case of peptic ulcer
      bleeding) to reduce the risk of continued or recurrent bleeding.

PMID- 14696298
TI  - Portal hypertensive bleeding.
AB  - Portal hypertension bleeding is a common and serious complication of cirrhosis.
      All patients with cirrhosis should undergo endoscopy and be evaluated for
      possible causes of current or future portal hypertensive bleeding. Possible
      causes of bleeding include esophageal varices, gastric varices, and PHG. Patients
      with esophageal varices at high risk of bleeding should be treated with
      nonselective beta-blockers for primary prevention of variceal hemorrhage. HVPG
      measurements represent the optimal way to monitor the success of pharmacologic
      therapy. EVL may be used in those with high-risk varices who do not tolerate beta
      blockers. When active bleeding develops, simultaneous and coordinated attention
      must be given to hemodynamic resuscitation, prevention and treatment of
      complications, and active control of bleeding. In cases of acute esophageal
      variceal (Fig. 5) and PHG bleeding, terlipressin, somatostatin, or octreotide
      should be started. Endoscopic treatment is provided for those with bleeding
      esophageal varices. If first-line therapy fails, TIPS or surgery may need to be
      performed. Unlike esophageal variceal or PHG bleeding, there is no established
      optimal treatment for gastric variceal bleeding. Individual and specific
      treatment modalities for acute gastric variceal bleeding must be calculated
      carefully after considering side effects.

PMID- 14696299
TI  - Lower gastrointestinal bleeding.
AB  - Lower gastrointestinal bleeding is defined as blood loss that originates from a
      source distal to the ligament of Treitz and results in hemodynamic instability or
      symptomatic anemia. Although approximately 10% to 15% of patients presenting with
      acute severe hematochezia have an upper gastrointestinal source of bleeding
      identified on upper endoscopy, the most common causes of lower gastrointestinal
      bleeding are diverticulosis, hemorrhoids, ischemic colitis, and angiodysplasia.
      As with upper gastrointestinal bleeding, lower gastrointestinal bleeding ceases
      spontaneously in most cases.

PMID- 14696300
TI  - Intestinal ischemia.
AB  - Ischemic injury to the gastrointestinal tract can threaten bowel viability with
      potential catastrophic consequences, including intestinal necrosis and gangrene.
      The presenting symptoms and signs are relatively nonspecific and diagnosis
      requires a high index of clinical suspicion. AMI often results from an embolus or
      thrombus within the SMA, although a low-flow state through an area of profound
      atherosclerosis may also induce severe ischemia. Because most laboratory and
      radiologic studies are nonspecific in early ischemia an aggressive approach to
      diagnosis with imaging of the splanchnic vasculature by mesenteric angiography is
      advocated. Various therapeutic approaches, including the infusion of vasodilators
      and thrombolytics, may then be used. Proper diagnosis and management of patients
      with AMI requires vigilance and a readiness to pursue an aggressive course of
      action.

PMID- 14696301
TI  - Diagnosis and management of cholecystitis and cholangitis.
AB  - Cholelithiasis is a prevalent condition in Western populations. Most cases are
      asymptomatic but complications can occur. Acute cholangitis, cholecystitis, and
      gallstone pancreatitis are the most common biliary tract emergencies and are
      usually caused by biliary calculi. Whenever possible, acute cholecystitis should
      be treated with early LC. AAC is an uncommon condition usually affecting patients
      with significant comorbidities. Treatment is usually with percutaneous
      cholecystostomy, which often is also the only required therapy. Endoscopic
      drainage is the preferred form of biliary decompression in acute cholangitis and
      these patients should subsequently undergo elective LC unless unfit for surgery.
      Effective and optimal management of biliary tract emergencies relies on close
      cooperation between gastroenterologist, surgeon, and radiologist.

PMID- 14696302
TI  - Emergency complications of acute and chronic pancreatitis.
AB  - Acute pancreatitis is a common disease with a relatively high morbidity and
      mortality. In contrast, chronic pancreatitis is a recurrent disease with multiple
      potential complications that occasionally require urgent intervention. This
      article focuses on the emergency complications of acute and chronic pancreatitis
      that require urgent intervention. Recent developments in the diagnosis and
      management of such complications are discussed.

PMID- 14696303
TI  - Fulminant hepatic failure.
AB  - FHF is a devastating illness of varied causes, carrying considerable mortality
      and affecting patients with previously healthy livers. The clinical presentation
      varies widely but encephalopathy is the defining criterion. Management requires a
      multidisciplinary approach, including rapid triage, monitoring, and referral to a
      transplantation center for further evaluation. Early prognostication and timely
      availability of donor livers are essential for a successful outcome. A donor
      shortage, however, continues to pose problems for both hepatologists and
      surgeons. Effective liver support devices may greatly prolong the window of
      opportunity to provide a donor liver, or alternatively to allow the native liver
      to regenerate. Despite decades of great progress in the field of liver support
      systems, the ideal system is still a long-cherished goal in hepatology. Hybrid
      systems have garnered most of the recent attention, but the quest for improved
      synthetic function has not yet been realized. It is hoped that rapid conceptual
      and technologic developments with respect to hybrid systems, hepatocyte
      transplantation, and xenografting will yield a safe and accessible tool for
      managing these critically ill patients. Controlled, multicenter trials in well
      defined patient groups and with standard outcome measures are essential to
      evaluate the clinical value of these devices. A better understanding of
      mechanisms responsible for liver cell death and multiorgan failure, and the
      development of strategies to enhance liver regeneration, may allow a more
      targeted approach to therapy.

PMID- 14696304
TI  - Liver emergencies during pregnancy.
AB  - Liver disease is an uncommon complication of pregnancy, although one that must be
      recognized early because of its potential for grave consequences for mother and
      child. Because of increased awareness and rapid triage of patients, maternal and
      fetal outcomes have improved significantly over the last 30 years.

PMID- 14696305
TI  - Bowel obstruction and pseudo-obstruction.
AB  - The gastroenterologist is frequently involved in the care of patients with bowel
      obstruction and pseudo-obstruction. In the case of obstruction, the central
      problem is determining which patients should be managed surgically. In both SBO
      and LBO, evidence of vascular compromise to the gut mandates surgical
      intervention. Most patients with pseudo-obstruction respond to conservative
      therapy or neostigmine. Endoscopic decompression is indicated in recalcitrant
      cases, with surgery reserved as a last resort.

PMID- 14696306
TI  - Severe acute diarrhea.
AB  - Acute diarrhea is commonly caused by an infection. Severe acute diarrhea warrants
      immediate medical evaluation and hospitalization. Indications for stool studies
      include fever; bloody diarrhea; recent travel to an endemic area; recent
      antibiotics; immunosuppression; and occupational risks, such as food handlers.
      Noninfectious causes include inflammatory bowel disease, radiation enteritis, and
      intestinal ischemia. Management of severe acute diarrhea includes intravenous
      fluid rehydration and empiric antibiotics. Use of antidiarrheal agents is
      controversial when invasive pathogens are suspected.

PMID- 14696307
TI  - Inflammatory bowel disease emergencies.
AB  - Emergency complications of IBD are rare, but may be life-threatening, require
      surgery, and result in permanent end organ damage. The most common complications
      associated with UC are fulminant colitis, toxic megacolon, and bleeding. Each of
      these complications may resolve with aggressive medical therapy but often result
      in a total proctocolectomy. The most common complications associated with CD are
      abscesses and intestinal obstruction. Although initial treatment includes medical
      treatment, these Crohn's-related complications usually require a surgical
      intervention and intestinal resection. Finally, the most common extraintestinal
      manifestations that present as an emergency include thromboembolic events, ocular
      complications, and hepatobiliary disease. Some of these complications may
      parallel the course of the underlying disease and respond to IBD treatment, but
      thromboemboli, uveitis, and PSC do not. In the last decade there has been an
      explosion of knowledge and discovery into the pathogenesis of IBD. These findings
      have led to better and earlier treatment of IBD that it is hoped will alter the
      natural course of disease and prevent many of the complications outlined in this
      article.

PMID- 14696308
TI  - Management of iatrogenic perforation.
AB  - Iatrogenic perforation of the gastrointestinal tract is a medical emergency and
      is inevitable. An endoscopist must maintain a high index of suspicion despite
      minimal or atypical symptoms and negative radiologic studies, because perforation
      is a complication with tremendous morbidity and mortality. The endoscopist must
      know how to manage this complication appropriately and to seek immediate surgical
      consultation. There is ongoing controversy about when a patient should undergo
      nonoperative or surgical therapy. An evidence-based approach to manage iatrogenic
      perforation is not possible. The trend in the modern era is to less invasive,
      nonoperative therapy, given advancements in ICU care and antibiotics. Laparoscopy
      or laparoscopic-assisted (minilaparotomy) surgery is also being increasingly used
      with outcomes comparable with conventional laparotomy. Experience and
      advancements in accessories have enabled endoscopic repair of iatrogenic
      perforation in many situations [84]. The management algorithms provided
      synthesize the pertinent literature into reasonable guidelines to follow.
      Ultimately, an individualized approach must be taken to manage the patient with
      an iatrogenic perforation.

PMID- 14696309
TI  - Behavioral mechanisms and the neurobiology of conditioned sexual responding.

PMID- 14696310
TI  - NMDA receptors in alcoholism.

PMID- 14696311
TI  - Processing and representation of species-specific communication calls in the
      auditory system of bats.

PMID- 14696312
TI  - Central nervous system control of micturition.

PMID- 14696313
TI  - The structure and physiology of the rat auditory system: an overview.

PMID- 14696314
TI  - Neurobiology of cat and human sexual behavior.

PMID- 14696315
TI  - Biodegradation of organic pollutants in the rhizosphere.

PMID- 14696316
TI  - Anaerobic dehalogenation of organohalide contaminants in the marine environment.
AB  - Microbially mediated dehalogenation processes contribute to the global cycling of
      both biogenic and anthropogenic halogenated organic compounds. Detailed
      information on biodegradation mechanisms for a variety of organohalides and on
      the microorganisms mediating these processes has greatly increased our
      understanding of the cycling and fate of these unique and widespread compounds in
      our environment. The marine environment appears to be a particularly rich source
      of dehalogenating microorganisms. It is well established by laboratory and field
      studies that anaerobic dehalogenation of sediment contaminants, such as PCBs,
      pesticides, and dioxins, occurs intrinsically and can be enhanced via various
      methods. Specific dehalogenating bacterial populations can be enriched on various
      organohalides. Biodehalogenation processes are likely to be significantly
      affected by the prevailing terminal electron-accepting condition, and thus,
      biotransformation of organohalide contaminants in marine and estuarine
      environments will vary as a function of the redox conditions within the sediment
      profile. Fundamental knowledge of the activities and interactions of
      dehalogenating microorganisms is providing a strong basis for development of new
      bioremediation technologies for removal of harmful halogenated compounds from our
      environment.

PMID- 14696317
TI  - Biotechnological application of metal-reducing microorganisms.

PMID- 14696318
TI  - Determinants of freeze tolerance in microorganisms, physiological importance, and
      biotechnological applications.

PMID- 14696319
TI  - Fungal osmotolerance.

PMID- 14696320
TI  - Mycotoxin research in South Africa.

PMID- 14696321
TI  - Electrophoretic karyotype analysis in fungi.
AB  - The resolution of chromosomal-sized DNAs by PFGE has many applications that
      include karyotyping, strain identification of similar species, characterization
      of transformed strains, building of linkage maps, and preparation of DNA for
      genomic analysis. Successful electrophoretic separation of chromosomes is an
      empiric process in which the initial concentration of intact chromosome-sized DNA
      and the optimization of electrophoretic parameters are the most important
      experimental variables. Nonetheless, inherent attributes of the genome
      architecture of certain species may thwart success. When a karyotype contains
      numerous chromosomes of the same size and/or many large (greater than 8 Mb)
      chromosomes, no amount of manipulation of the electrophoretic parameters will
      resolve individual chromosome bands using present technology. Further, fungi
      display a surprising amount of intraspecific variation in both chromosome number
      and size, making it difficult to establish a standard "reference" karyotype for
      many species. Although PFGE is not a panacea for bringing genetics to species
      that lack classical genetic systems, it often does provide a way for developing a
      molecular linkage map in the absence of a formal genetic system. It is far faster
      than parasexual analysis in the discovery of linkage relationships. For genomics
      projects, DNA can be recovered from pulsed field gels and used to prepare
      chromosome-specific libraries. Where whole genome sequencing strategies are used,
      chromosomes separated by PFGE provide an anchor for sequencing data.
      Electrophoretic karyotypes can be probed with anonymous pieces of DNA from
      bacterial artificial chromosome (BAC) contigs, thereby facilitating the building
      of physical maps. In conclusion, despite its shortcomings, the PFGE technique
      underlies much of our current understanding of the physical nature of the fungal
      genome.

PMID- 14696322
TI  - Tissue infection and site-specific gene expression in Candida albicans.
AB  - C. albicans is able to survive and proliferate in and on a range of different
      tissues, either as a commensal or as a pathogen. During the different stages and
      types of infection, the fungal cells need a broad flexibility since each anatomic
      site has its own set of environmental pressures (Calderone and Fonzi, 2001). The
      fact that C. albicans possesses gene families encoding known virulence factors
      may reflect an adaptation to the wide range of environmental pressures that a C.
      albicans cell is likely to encounter during growth in vivo. In fact, specific
      members of each family are likely to be differentially expressed in different
      tissues and at different stages of infection, suggesting that these features have
      evolved as a consequence of these pressures. It remains to be investigated
      whether the members of the families have different functions or if they are just
      proteins with the same function but adapted to the specific demands of each
      anatomical site. Furthermore, with a few exceptions, the regulatory mechanisms
      responsible for the differential expression of individual members within gene
      families are not clear. However, the use of microarrays and other high-throughput
      technologies will certainly accelerate our knowledge of tissue-specific gene
      expression in microorganisms and will therefore help to understand why C.
      albicans is such a successful fungal commensal and pathogen.

PMID- 14696323
TI  - LuxS and autoinducer-2: their contribution to quorum sensing and metabolism in
      bacteria.

PMID- 14696324
TI  - Microbiological contributions to the search for extraterrestrial life.

PMID- 14696325
TI  - Taxonomy of the virus family Flaviviridae.

PMID- 14696326
TI  - Molecular biology of flaviviruses.

PMID- 14696327
TI  - Flavivirus structure and membrane fusion.

PMID- 14696328
TI  - Kunjin RNA replication and applications of Kunjin replicons.
AB  - The Kunjin virus (KUNV) has provided a useful laboratory model for Flavivirus RNA
      replication. The synthesis of progeny RNA(+) strands occurs via asymmetric and
      semiconservative replication on a  template of recycling double-stranded RNA
      (dsRna) or replicative form (RF). Kinetics of viral RNA synthesis indicated a
      cycle period of about 15 min during which, on average, a single nascent RNA (+)
      strand displaces the pre-existing RNA(+) strand in the replicative intermediate.
      Data on the composition of the replication complex (RC) in KUNV-infected cells
      were obtained from several sources, including analyses of the partially-purified
      still active RC, immunogold labeling of cryosections using monospecific
      antibodies to the nonstructural proteins and to the dsRNA,
      radioimmunoprecipitations of cell lysates using antibodies to dsRNA and to an RC
      associated cell marker, and pull-down assays of cell lysates using fusion
      proteins GST-NS2A and GST-NS4A. These results yeilded a consensus composition of
      NS1, NS2A, NS3, NS4A, and NS5 strongly associated with the dsRNA template. The RC
      was located in induced membranes described as vesicle packets. The RNA-dependent
      RNA polymerase activity late in infection did not require continuing protein
      synthesis. Replication of genomic RNA was completely dependent on the presence of
      conserved complementary or cyclization sequences near the 5' and 3' ends.
      Assembly of the RC during translation in cis and the relationships, particularly
      those of NS1 and NS5 among the components, were deduced from an extensive set of
      complementation experiments in trans involving mutations/deletions in all the
      nonstructural proteins and use of KUN or alphahavirus replicons as helpers. The
      KUN replicon has found useful applications also as a noncytopathic vector for the
      continuing expression of foreign genes, delivered either as packaged RNA or as
      plasmid DNA.

PMID- 14696329
TI  - Antigenic structure of flavivirus proteins.
AB  - The increased activity of Dengue virus in the tropical regions of the world and
      the recent movement of West Nile virus from the eastern to the western hemisphere
      emphasize the fact that vector-borne flaviviruses are medically important
      emerging infectious diseases. These facts warrant continued efforts to decode all
      facets of flavivirus immunology. This chapter reviews current understanding of
      the antigenic fine structure of flaviviral structural and nonstructural (NS)
      proteins and their involvement in B- an T-cell host responses. The virion
      structural glycoprotein E elicits both virus-neutralizing antibodies and
      antiviral Th-cell responses. Consistent with the current hypothesis of the MHC
      class I pathway of protein processing, immunodominant flaviviral Tc-cell epitopes
      mainly reside on the NS proteins. To prepare effective and inexpensive subunit
      vaccines, we will need to continue to better understand these structure-function
      relationships of  flavivirus proteins.

PMID- 14696330
TI  - 5'- and 3'-noncoding regions in flavivirus RNA.

PMID- 14696331
TI  - Manipulation of cell surface macromolecules by flaviviruses.
AB  - Cell surface macromolecules play a crucial role in the biology and pathobiology
      of flaviviruses, both as receptors for virus entry and as signaling molecules for
      cell-cell interactions in the processes of vascular permeability and
      inflammation. This review examines the cell tropism and pathogenesis of
      flaviviruses from the standpoint of cell surface molecules, which have been
      implicated as receptors in both virus-cell as well as cell-cell interactions. The
      emerging picture is one that encompasses extensive regulation and interplay among
      the invading virus, viral immune complexes, Fc receptors, major
      histocompatibility complex antigens, and adhesion molecules.

PMID- 14696332
TI  - Origins, evolution, and vector/host coadaptations within the genus Flavivirus.
AB  - Although viruses in the genus Flavivirus share complex antigenic
      interrelationships, they can be divided into four phylogenetic/ecological groups:
      two mosquito-borne groups, a tick-borne group, and nonvectored viruses. These
      divisions largely reflect the selective constraints imposed on the viruses by the
      vertebrate hosts, the invertebrate vectors, and the associated ecologies.
      Phylogenetic trees based on the flavivirus genetic sequence show characteristic
      branching patterns that reflect these groupings. This review describes the
      evolution and possible origins of individual flaviviruses, correlating ecological
      and epidemiological characteristics with their phylogenies and geographic
      dispersal. It will also become apparent that many of the phylogenetic lineages
      that define species diverged relatively recently, and the subsequent dispersal
      and epidemiology of these viruses have therefore been significantly influenced by
      increasing human population densities and activities such as recreation,
      urbanization, land reclamation, transportation, and deforestation. This review
      also considers some of the likely implications of persistent/chronic infections
      in relation to virus dispersal and recombination between related flaviviruses on
      phylogenetic analysis and vaccine development strategies.

PMID- 14696334
TI  - Lineage specific differentiation of mouse ES cells: formation and differentiation
      of early primitive ectoderm-like (EPL) cells.

PMID- 14696333
TI  - Microevolution and virulence of dengue viruses.
AB  - The evolution of dengue viruses has had a major impact on their virulence for
      humans and on the epidemiology of dengue disease around the world. Although
      antigenic and genetic differences in virus strains had become evident, it is
      mainly due to the lack of animal models of disease that has made it difficult to
      detect differences in virulence of dengue viruses. However, phylogenetic studies
      of many different dengue virus samples have led to the association between
      specific genotypes (within serotypes) and the presentation of more or less severe
      disease. Currently, dengue viruses can be classified as being of
      epidemiologically low, medium, or high impact; i.e., some viruses may remain in
      sylvatic cycles of little or low transmissibility to humans, others produce
      dengue fever (DF) only, and some genotypes have been associated with the
      potential to cause the more severe dengue hemorrhagic fever (DHF) and dengue
      shock syndrome (DSS) in addition to DF. Although the factors that contribute to
      dengue virus epidemiology are complex, studies have suggested that specific viral
      structures may contribute to increased replication in human target cells and to
      increased transmission by the mosquito vector; however, the immune status and
      possibly the genetic background of the host are also determinants of virulence or
      disease presentation. As to the question of whether dengue viruses are evolving
      toward virulence as they continue to spread throughout the world, phylogenetic
      and epidemiological analyses suggest that the more virulent genotypes are now
      displacing those that have lower epidemiological impact; there is no evidence for
      the transmission of antigenically aberrant, new strains.

PMID- 14696335
TI  - Differentiation of F1 embryonic stem cells into viable male and female mice by
      tetraploid embryo complementation.

PMID- 14696336
TI  - Hematopoietic commitment of ES cells in culture.

PMID- 14696337
TI  - In vitro differentiation of mouse embryonic stem cells: hematopoietic and
      vascular cell types.

PMID- 14696338
TI  - In vitro differentiation of mouse embryonic stem cells to hematopoietic cells on
      an OP9 stromal cell monolayer.

PMID- 14696339
TI  - In vitro differentiation of mouse ES cells: hematopoietic and vascular
      development.

PMID- 14696340
TI  - In vitro differentiation of mouse ES cells into hematopoietic, endothelial, and
      osteoblastic cell lineages: the possibility of in vitro organogenesis.

PMID- 14696341
TI  - Development of hematopoietic repopulating cells from embryonic stem cells.

PMID- 14696342
TI  - The in vitro differentiation of mouse embryonic stem cells into neutrophils.
AB  - A reliable and effective in vitro differentiation system is described for the
      production of functional neutrophils from mouse embryonic stem (ES) cells. A
      three-step culture method was developed that enables abundant production and
      effective harvesting of mature neutrophils at high purity without sorting.
      Utilization of the OP9 stromal cell line, which does not produce macrophage
      colony stimulating factor (M-CSF) was found to enhance the number, percentage and
      duration of neutrophils produced. Based on a number of criteria, morphologically
      and functionally mature neutrophils can be produced using this method in
      approximately 16 days. This differentiation system provides a useful model system
      for studying neutrophil development and maturation in vitro and the many factors
      that regulate this process. Morphologically mature ES-derived neutrophils can be
      grown in culture that produce superoxide, flux calcium and directionally respond
      to the chemoattractant MIP-2. In addition, they express the granulocyte markers
      Gr-1 and the neutrophil specific antigen, as well as specific chloroacetate
      esterase. Interestingly, during their development in culture, regional areas of
      apparent neutrophil production can be identified that recapitulate certain
      aspects of the marrow environment. As ES cells can be genetically modified, this
      system enables evaluation of the effects of specific genetic alterations on
      neutrophil differentiation and function.

PMID- 14696343
TI  - Development and analysis of megakaryocytes from murine embryonic stem cells.

PMID- 14696344
TI  - Development of lymphoid lineages from embryonic stem cells in vitro.
AB  - Lymphocyte development proceeds through highly ordered and regulated stages, as
      multipotent hematopoietic progenitors differentiate into lineage-defined
      progenitors, and ultimately into mature effector cells. The ability to generate
      lymphocytes from embryonic stem (ES) cells in vitro should facilitate the study
      of these complex differentiation steps by providing a model system in which the
      effects of genetic and nongenetic manipulations can be examined in a controlled
      setting. These advances may also contribute to future therapeutic approaches. In
      this article, we describe the procedure for generating functional lymphocytes
      from mouse ES cells.

PMID- 14696345
TI  - Probing dendritic cell function by guiding the differentiation of embryonic stem
      cells.

PMID- 14696346
TI  - Gene targeting strategies for the isolation of hematopoietic and endothelial
      precursors from differentiated ES cells.

PMID- 14696347
TI  - Establishment of multipotent hematopoietic progenitor cell lines from ES cells
      differentiated in vitro.

PMID- 14696348
TI  - Vasculogenesis and angiogenesis from in vitro differentiation of mouse embryonic
      stem cells.

PMID- 14696349
TI  - ES cell differentiation to the cardiac lineage.

PMID- 14696350
TI  - Bone nodule formation via in vitro differentiation of murine embryonic stem
      cells.

PMID- 14696351
TI  - In vitro differentiation of mouse ES cells: bone and cartilage.

PMID- 14696352
TI  - Development of adipocytes from differentiated ES cells.

PMID- 14696353
TI  - In vitro differentiation of embryonic stem cells into hepatocytes.

PMID- 14696354
TI  - Differentiation of mouse embryonic stem cells into pancreatic and hepatic cells.
AB  - Here, we present efficient strategies to differentiate ES cells either into
      pancreatic or into hepatic cell types. We recommend a strategy to select nestin+
      cells, an early progenitor cell type with high developmental plasticity, followed
      by differentiation induction with specific growth and extracellular matrix
      factors into pancreatic and hepatic cell types. Cells differentiating via nestin+
      cells into the pancreatic and hepatic lineage expressed tissue-specific genes.
      Proteins characteristic for mature endocrine pancreatic or hepatic cells were
      synthesized and released. Further, a histotypic "spinner" culture system was
      introduced to generate mature insulin- and albumin-producing cells at high
      efficiency.

PMID- 14696355
TI  - Generating CNS neurons from embryonic, fetal, and adult stem cells.

PMID- 14696356
TI  - Defined conditions for neural commitment and differentiation.
AB  - The efficiency of monolayer differentiation establishes that commitment of ES
      cells to a neural fate needs neither multicellular aggregation nor extrinsic
      inducers. The entire process by which pluripotent ES cells acquire neural
      specification can be visualized and recorded at the level of individual colonies.
      Furthermore this simple culture system is amenable to cellular and molecular
      dissection, promising to yield new insights into the mechanism underlying neural
      determination in mammals and perhaps to deliver the goal of "directed"
      homogeneous differentiation of ES cells.

PMID- 14696357
TI  - Development of melanocytes from ES cells.

PMID- 14696358
TI  - Isolation and culture of embryonic germ cells.

PMID- 14696359
TI  - Gene trap mutagenesis in embryonic stem cells.

PMID- 14696361
TI  - Gene-based chemical mutagenesis in mouse embryonic stem cells.

PMID- 14696360
TI  - Gene trap vector screen for developmental genes in differentiating ES cells.

PMID- 14696362
TI  - Growth and differentiation of cynomolgus monkey ES cells.

PMID- 14696363
TI  - Isolation, characterization, and differentiation of human embryonic stem cells.

PMID- 14696364
TI  - Factors controlling human embryonic stem cell differentiation.

PMID- 14696365
TI  - Development of cardiomyocytes from human ES cells.

PMID- 14696366
TI  - How Bijvoet made the difference: the growing power of anomalous scattering.

PMID- 14696367
TI  - SOLVE and RESOLVE: automated structure solution and density modification.
AB  - SOLVE and RESOLVE have shown that it is possible to automate a significant part
      of the macromolecular X-ray structure determination process. The key elements of
      seamless and compatible subprograms, scoring algorithms, and error-tolerant
      software systems have been important in implementing these programs. The
      principles used in SOLVE and RESOLVE can be applied to other aspects of structure
      determination as well, suggesting that full automation of the entire structure
      determination process from scaling diffraction data to a refined model will be
      possible in the near future.

PMID- 14696368
TI  - Automatic solution of heavy-atom substructures.

PMID- 14696369
TI  - Use of noble gases xenon and krypton as heavy atoms in protein structure
      determination.

PMID- 14696370
TI  - Phasing on rapidly soaked ions.

PMID- 14696371
TI  - The Bijvoet-difference Fourier synthesis.

PMID- 14696372
TI  - Isomorphous difference methods.

PMID- 14696373
TI  - X-ray crystallographic structure determination of large asymmetric macromolecular
      assemblies.

PMID- 14696374
TI  - Multidimensional histograms for density modification.

PMID- 14696375
TI  - Docking of atomic models into reconstructions from electron microscopy.

PMID- 14696376
TI  - ARP/wARP and automatic interpretation of protein electron density maps.

PMID- 14696377
TI  - TEXTAL system: artificial intelligence techniques for automated protein model
      building.

PMID- 14696378
TI  - Applications for macromolecular map interpretation: X-AUTOFIT, X-POWERFIT, X
      BUILD, X-LIGAND, and X-SOLVATE.

PMID- 14696379
TI  - Macromolecular TLS refinement in REFMAC at moderate resolutions.

PMID- 14696380
TI  - Structural information content at high resolution: MAD versus native.

PMID- 14696381
TI  - Full matrix refinement as a tool to discover the quality of a refined structure.

PMID- 14696382
TI  - Validation of protein structures for protein data bank.

PMID- 14696383
TI  - New tools and data for improving structures, using all-atom contacts.

PMID- 14696384
TI  - Promise of advances in simulation methods for protein crystallography: implicit
      solvent models, time-averaging refinement, and quantum mechanical modeling.

PMID- 14696385
TI  - Modeller: generation and refinement of homology-based protein structure models.

PMID- 14696386
TI  - GRASP2: visualization, surface properties, and electrostatics of macromolecular
      structures and sequences.
AB  - The widespread use of the original version of GRASP revealed the importance of
      the visualization of physicochemical and structural properties on the molecular
      surface. This chapter describes a new version of GRASP that contains many new
      capabilities. In terms of analysis tools, the most notable new features are
      sequence and structure analysis and alignment tools and the graphical integration
      of sequence and structural information. Not all the new GRASP2 could be described
      here and more capabilities are continually being added. An on-line manual,
      details on obtaining the software, and technical notes about the program and the
      Troll software library can be found at the Honig laboratory Web site
      (http://trantor.bioc.columbia.edu).

PMID- 14696387
TI  - Simplicial neighborhood analysis of protein packing (SNAPP): a computational
      geometry approach to studying proteins.

PMID- 14696388
TI  - Tools and databases to analyze protein flexibility; approaches to mapping implied
      features onto sequences.

PMID- 14696389
TI  - Looking behind the beamstop: X-ray solution scattering studies of structure and
      conformational changes of biological macromolecules.

PMID- 14696390
TI  - Identifying importance of amino acids for protein folding from crystal
      structures.

PMID- 14696391
TI  - [Effect of painting work on alcoholic liver dysfunction].
AB  - The effect of painting on alcoholic liver dysfunction was investigated. The
      subjects were male workers engaged in small-scale enterprises under contract to
      with heavy industries. Painting involved metal cleaning and painting, and the air
      concentrations of organic solvents were frequently high. The study population
      consisted of 1,157 male workers over 40 yr of age. Of them, 85 were painters
      engaged for a mean duration of 20.9 +/- 9.8 yr. There was no significant
      difference in GOT and GPT between painters who did not drink and non-painters who
      did not drink, but GOT and GPT were significantly higher in painters drinking
      several days a week than in non-painters. A past history of hepatitis affected
      GOT, GPT and gamma-GTP. Painting, daily alcohol consumption, drinking frequency
      and body mass index affected gamma-GTP. A questionnaire survey of hepatitis was
      also conducted in 206 male workers (age range 18-67 yr). Of them, 134 were
      painters (mean duration of painting, 16.8 +/- 10.4 yr). This questionnaire survey
      showed that 13 painters (9.6% of the painters) and two non-painters (2.6% of the
      non-painters) had a history of hepatitis. Of the 13 painters, five painters had a
      history of hepatitis C and four had a history of alcoholic hepatitis. All of
      these 13 painters had the habit of drinking. This study indicated that painting
      had little effect on the liver function in painters not drinking, but increased
      alcoholic liver dysfunction in painters with the drinking habit.

PMID- 14696392
TI  - [Effect of professional oral prophylaxis on the general health perceptions and
      lifestyles in workers of a worksite].
AB  - The present study was undertaken to look at the effect of professional oral
      prophylaxis on the general health perceptions and lifestyle in workers at a
      worksite in Aichi-ken. Dental check-ups and three kinds of questionnaires (SAS:
      The Social Adjustment Scale, MOS: The Medical Outcomes Study and the nutrition)
      were used in this investigation for three years from 1998. By means of the
      stratified sampling method, the participants were 265 workers separated into a
      case and a control group, who work for a pharmaceutical company (201 males, 64
      females, average age 35.6 +/- 0.7 yr old). All participants gave their consent to
      the study. As in the case group, dental hygienists scaled their teeth and gave
      each of them appropriate advice about their oral health twice in a year. MOS,
      SAS, nutrition and oral health in the case and control groups were compared with
      the baseline, third and the final year. The results were as follows; 1) There was
      significant difference in energy, protein, fat, fish and meats sufficiency rates
      (p < 0.05) and a higher tendency towards consuming sugar, potassium (K), calcium
      (Ca), iron (Fe) and Fiber (p < 0.10) in the control group, but there were no
      significant differences in the other nutrients in the case and control groups. 2)
      There were significant differences in the number of decayed teeth in the case
      group, and in the number of filled teeth and decayed teeth in the control group.
      The gingival condition (CPI = 0) in the case group tended to be higher healthier
      than the control group, 3) In the MOS questionnaire, the case group was better or
      not worse in health perceptions scales, pain scales and mental health scales than
      the control group. 4) In the SAS questionnaire, the case group was better or not
      worse in the work and the social scales than the control group. It was concluded
      that oral health, social health and consciousness of health tended to improve by
      dental intervention.

PMID- 14696393
TI  - [Risk factors for low back pain among taxi drivers in Japan].
AB  - We conducted a questionnaire study on low back pain (LBP) and working conditions
      among male taxi drivers employed in the company in Fukuoka city in order to
      investigate the occurrence of LBP and occupational factors related to LBP among
      taxi drivers. The study was undertaken through two questionnaires, the first
      conducted in 1999 (n = 280, first cross-sectional study), the second conducted in
      2001 (n = 284, second cross-sectional study). The questionnaire results were used
      to conduct two analyses: 1) the one-year prevalence of LBP and the relationship
      between LBP and occupational factors in the second cross-sectional study, and 2)
      the incidence of LBP and the relationship between LBP and occupational factors
      from the first to the second cross-sectional study in the longitudinal study. The
      incidence cases were defined as subjects who met the following conditions: those
      who had never experienced LBP at the time of the first study but had experienced
      LBP during the previous year at the time of the 2nd study. The one-year
      prevalence (45.8%) of LBP among taxi drivers was comparable to rates reported for
      other occupational drivers in which LBP occurs frequently. This result indicates
      that LBP is an important health problem for taxi drivers, and an urgent
      occupational safety and health management issue. The two-year incidence of LBP
      among the taxi drivers was estimated at 25.9%. LBP was significantly related with
      the suitability of the driver's seat pan, total mileage on the taxi (total
      mileage), the level of uncomfortable vibrations on the road, job stress and time
      employed as a taxi driver. Importantly, the prevalence of LBP increased with
      increasing total mileage, a finding which had not previously been reported. The
      findings of this study also suggest that ergonomic problems with the driver's
      seat pan, whole-body vibration (WBV) and job stress may contribute to LBP among
      taxi drivers. Further study is needed to confirm how total mileage contributes to
      LBP. Furthermore, WBV during normal use of taxies should be measured in order to
      evaluate the association between WBV and LBP.

PMID- 14696394
TI  - [A cohort study on the relationship between microscopic work and decreased visual
      acuity].

PMID- 14696395
TI  - Carbon monoxide hemoglobin and bilirubin metabolism in adult living-related liver
      transplantation.
AB  - BACKGROUND/AIMS: Hemeoxygenase-1 produces carbon monoxide as a byproduct of
      hemoglobin metabolism. The present study examines the relationship between carbon
      monoxide production and hyperbilirubinemia following adult living-related liver
      transplantation with special attention to the contribution of shear stress in
      retarding regeneration. METHODOLOGY: Case records from 16 patients who underwent
      adult living-related liver transplantation from March 1999 to May 2001 were
      reviewed. Patients were divided into group A (graft weight: recipient body weight
      ratio > or = 1) and group B (graft weight: recipient body weight ratio < 1).
      Clinical characteristics and outcome in the two groups were compared. RESULTS:
      Total serum bilirubin concentration and the direct: total serum bilirubin
      concentration were higher in group B than group A (p < 0.01). Further, the carbon
      monoxide-hemoglobin concentration correlated with the total serum bilirubin
      concentration (r = 0.81, p < 0.0001) and also was higher in group B than group A
      (p < 0.05). The arterial: ketone body ratio rose similarly during the first week
      in both groups. CONCLUSIONS: Persistent hyperbilirubinemia in small-for-size
      grafts and concomitant carbon monoxide-hemoglobinemia reflect both parenchymal
      and Kupffer cell dysfunction. The role of shear stress in the portal system and
      its relationship to portal hypertension are discussed.

PMID- 14696396
TI  - Sporadic colorectal cancer in elderly people.
AB  - BACKGROUND/AIMS: The mechanism of the development of cancer in old age is not
      well understood in various cancers, especially colorectal cancer. Colorectal
      cancer in elderly patients often shows a high frequency of proximal colon cancer.
      Microsatellite instability cancers are often found in the proximal colon and show
      a lower incidence of p53 abnormality. While the aberrant expression of p53 is
      more frequent in the distal colon. To investigate the carcinogenesis of
      colorectal cancer in elderly patients, we studied the genetic background of these
      patients regarding microsatellite instability and the aberrant expression of p53.
      METHODOLOGY: In the present study, we examined the clinicopathological features
      and the frequency of p53 abnormality in elderly patients compared to younger
      patients, and the frequency of microsatellite instability in elderly patients. In
      microsatellite instability cancer, immunoreactivity of hMSH2 and hMLH1 were also
      examined. RESULTS: Colorectal cancer in elderly patients is associated with
      proximal location of the cancer (p = 0.008). Microsatellite instability was
      observed in only 1 case (2.8%). The immunoreactivity of hMLH1 showed negative
      staining in malignant glands. The frequency of aberrant expression of p53 showed
      no significant difference between two groups. CONCLUSIONS: We found colorectal
      cancer more frequently in proximal colon in elderly patients than in younger
      patients, and microsatellite instability frequency in elderly patients (2.8%) was
      lower than reported microsatellite instability frequency in sporadic colorectal
      cancer patients. Moreover, the frequency of aberrant expression of p53 did not
      differ between the two groups. In the present study, microsatellite instability
      appeared to be less important for the carcinogenesis of colorectal cancer in
      elderly patients as compared to younger patients.

PMID- 14696397
TI  - Type-2 hepatorenal syndrome and refractory ascites: role of transjugular
      intrahepatic portosystemic stent-shunt in eighteen patients with advanced
      cirrhosis awaiting orthotopic liver transplantation.
AB  - BACKGROUND/AIMS: TIPS (transjugular intrahepatic portosystemic stent-shunt) has
      been used increasingly in the management of refractory variceal bleeding. Its
      role in the management of refractory ascites and hepatorenal syndrome still
      awaits further prospective studies. Type-2 hepatorenal syndrome is a moderate
      steady renal impairment. It arises spontaneously and it is the main mechanism of
      refractory ascites. Precipitating factors may lead to type-1 hepatorenal
      syndrome. Hepatorenal syndrome is a common complication of advanced cirrhosis
      with a 3-month mortality of more than 90% unless treated by orthotopic liver
      transplantation. However, because of the short survival of patients with
      hepatorenal syndrome and the limited availability of organs, only a small
      percentage of patients with hepatorenal syndrome can actually reach orthotopic
      liver transplantation. That is why awaiting orthotopic liver transplantation we
      have submitted some suitable patients to a TIPS setting. METHODOLOGY: We have
      considered eighteen consecutive patients affected by advanced cirrhosis (Child
      Pugh 10-12) awaiting orthotopic liver transplantation and suitable for TIPS
      treatment for the presence of type-2 hepatorenal syndrome (10 males, average age
      44.5). The criteria for the diagnosis of hepatorenal syndrome and refractory
      ascites have been effected according to a consensus recommendation. Organic
      kidney disease was excluded. After mild intravenous sedation and analgesia a
      puncture needle was advanced transjugular in a catheter through the inferior cava
      into one of the three hepatic veins. Subsequently, an intrahepatic branch of the
      portal vein was punctured and the shunt was established by the implantation of
      Wallstent (diameter 10 mm; Boston, Scientific, Natick, MA). In all patients, we
      compared serum creatinine, creatinine-clearance, sodium excretion and urine
      volume before the intervention and 12 weeks after TIPS. The differences among
      groups were analyzed using paired Student's t-test. RESULTS: The stent shunt was
      successfully established in all eighteen patients. Complications occurred in 4
      patients (temperature above 38 degrees C or vomiting). No patients have developed
      hepatic encephalopathy resistant to medical treatment. As for the ascites a
      complete response with total remission of ascites was obtained in eight patients,
      while a partial response with the presence of sonographically detectable ascites-
      without the need of paracentesis--was obtained in ten patients. As regards renal
      functional parameters we have evidenced a significant improvement after TIPS.
      CONCLUSIONS: We can notice how the setting of TIPS, at least in the presented
      case, has allowed the treatment of ascites and, furthermore, has lead to
      improvement of the renal functional parameters. It all implies the enormous
      advantage of a better management of the patient waiting for orthotopic liver
      transplantation and, most of all, the advantage of preparing the patient for the
      surgical intervention with normal renal functional parameters: in fact, it is
      well known that the increase of serum creatinine influences the pre- and post
      orthotopic liver transplantation course, and in particular can modify the
      mortality rate of the patient list. The lack of effective alternative treatment
      modalities and the almost universally fatal outcome of hepatorenal syndrome make
      TIPS an attractive option in the treatment of hepatorenal syndrome as a bridge to
      orthotopic liver transplantation.

PMID- 14696398
TI  - Reduced p16 expression correlates with lymphatic invasion in colorectal cancers.
AB  - BACKGROUND/AIMS: P16, the tumor suppressor gene, plays a crucial role in the most
      important regulatory pathway involved in the G1/S transition, but its role in
      gastrointestinal neoplasia remains unclear. METHODOLOGY: To evaluate the possible
      p16 role in the development of colonic neoplasms, the authors studied p16
      immunohistochemical expression of 84 lesions of colorectal cancers, 6 lesions of
      hyperplastic polyps, 59 lesions of adenomas and 8 lesions of carcinoma in
      adenoma. Immunohistochemical staining was processed by streptavidin biotin
      technique. The degree of expression pattern was classified into four types:
      absent, scattered, or nested, diffuse. Also, the correlation between
      immunohistochemical expression pattern and clinicopathological features was
      evaluated. RESULTS: Compared with normal colonic mucosa, in which virtually no
      p16 expression was observed, p16 was overexpressed in hyperplastic polyps
      (33%:2/6) adenomas (46%:27/59), carcinoma in adenoma (88%:7/8) and in
      adenocarcinomas (98%:82/84). In colorectal cancers, when divided into positive
      (diffuse or nested) and negative (absent or scattered) subgroups, the negative
      group showed a higher ratio of lymphatic infiltration (p = 0.04), a higher ratio
      of deeper invasion (p < 0.01) and a higher ratio showing histology of mucinous
      carcinoma or poorly differentiated adenocarcinoma (p < 0.01). CONCLUSIONS: In
      colorectal cancers, a significant correlation of reduced p16 expression and
      lymphatic invasion was observed, which suggested and colorectal cancers with
      reduced p16 expression have more aggressive potential of lymphatic infiltration.
      Also a significant correlation between the overexpression of p16 and tumor
      progression was demonstrated.

PMID- 14696399
TI  - Evaluation of a newly developed office-based stool test for detecting
      Helicobacter pylori: an extensive pilot study.
AB  - BACKGROUND/AIMS: Several strategies have been used to detect Helicobacter pylori
      (Hp) infection along two lines: 1) direct detection of the bacteria, and 2)
      detection of antigen-antibody assay against Hp. The non-invasive methods include
      ELISA test of serum, salivary and urine, urea breath test, and detection of Hp
      antigen in stool. The latter method (HpSA) has been proven reliable and better
      than the ELISA test, for it can detect current Hp infection and is suitable for
      post-treatment follow-up. Now, a new commercial kit, ImmunoCard STAT HpSA
      (Meridian Bioscience Europe) has been developed to detect stool Hp antigen. It is
      simpler and less time-consuming than HpSA. The aim was to examine whether
      ImmunoCard STAT HpSA is qualified for diagnosis of Hp infection. METHODOLOGY: 253
      patients (163 men, 90 women, mean age: 53.3 +/- 13.9 y/o, range: 19-89 y/o) were
      enrolled in this study. All of them had undergone gastroendoscopy and urea breath
      test. 207 patients were diagnosed with peptic ulcer and 46 with gastritis. Stool
      samples were collected within 3 days of their visit for gastroendoscopy and were
      sent for the Immunocard test. RESULTS: 118 patients were diagnosed with Hp
      infection and of these, 113 were interpreted as positive by means of the
      Immunocard test. Among the other 135 patients without Hp infections, 123 were
      interpreted as negative by means of the Immunocard test. Sensitivity and
      specificity were 95.8% and 91.1%, and positive and negative predictive values
      were 90.4% and 96.1%. CONCLUSIONS: The ImmunoCard STAT HpSA had high sensitivity,
      and specificity and could be used for mass screening. We concluded that it is a
      rapid, simple, cheap, reliable, and non-invasive strategy to detect current Hp
      infection and can be used in post-Hp eradication follow-up in Taiwan.

PMID- 14696400
TI  - Prevention of variceal recurrence, bleeding, and death in cirrhosis patients with
      hypersplenism, especially those with severe thrombocytopenia.
AB  - BACKGROUND/AIMS: We investigated the impact of different treatments on the
      prognosis of cirrhosis patients with esophageal varices and thrombocytopenia.
      METHODOLOGY: This prospective study enrolled 52 cirrhosis patients with
      esophageal varices and hypersplenism (platelet count < 50,000/mm3). In 26
      patients, endoscopic variceal ligation plus partial splenic embolization were
      performed, while endoscopic variceal ligation alone was done in 26 patients.
      Endoscopic variceal ligation was repeated until complete eradication of varices
      was achieved. Partial splenic embolization was performed using the Seldinger
      method and embolic material was injected until a 60% to 80% reduction of splenic
      blood flow was achieved. The primary endpoints during the follow-up period
      included recurrence of varices, variceal bleeding, and death. RESULTS: Comparison
      of endoscopic variceal ligation plus partial splenic embolization with endoscopic
      variceal ligation alone by multivariate analysis showed a relative risk ratio of
      0.390 (95% CI [0.178-0.854]; p = 0.024) for new varices, 0.191 (95% CI [0.047
      0.780]; p = 0.021) for variceal bleeding, and 0.193 (95% CI [0.053-0.699]; p =
      0.012) for death. CONCLUSIONS: These results suggest that endoscopic variceal
      ligation plus partial splenic embolization can prevent variceal recurrence,
      bleeding, and death in cirrhosis patients with esophageal varices and
      thrombocytopenia.

PMID- 14696401
TI  - The Immunohistochemical expression of endothelial cell differentiation gene-2
      receptor in human colorectal adenomas.
AB  - BACKGROUND/AIMS: The EDG-2 (endothelial cell differentiation gene-2) has been
      characterized as one of the high-affinity receptors of lysophosphatidic acid: an
      extracellular lipid mediator which can induce tumor progression. Recent studies
      have revealed that EDG-2 plays an important role in various pathological events
      including cell proliferation and tumor development. The investigation of EDG-2 is
      thus considered important for eliciting the mechanism of tumorigenesis. However,
      in colorectal tissue, the clinical significance of EDG-2 expression remains
      unclear. In the current study, we examined the immunohistochemical expression of
      EDG-2 in colorectal mucosa and adenoma, and clarified its relation with the
      clinicopathological features. METHODOLOGY: One hundred and sixty-one colorectal
      polyps were resected endoscopically or surgically at our institute from 2000 to
      2001. According to the degree of dysplasia, adenomas were grouped into two
      categories: low-grade (mild or moderate dysplasia) and high-grade (severe
      dysplasia or carcinoma in situ). We investigated EDG-2 expression by
      immunohistochemistry. RESULTS: EDG-2 was expressed almost exclusively in the
      cytoplasm in colorectal normal mucosa and adenoma. EDG-2 expression in normal
      mucosa and adenoma was 8% and 76%, respectively. EDG-2 expression was increased
      in low-grade adenoma compared with that in normal mucosa (P < 0.001). EDG-2
      expression was significantly greater in adenomas with larger diameters (P <
      0.001). CONCLUSIONS: We demonstrated that EDG-2 expression was increased in the
      early stage of adenoma. A significant correlation between EDG-2 expression and
      the size of the adenomas suggests that EDG-2 may play an important role in the
      growth of these adenomas.

PMID- 14696403
TI  - Combined intraarterial 5-fluorouracil and intramuscular interferon-alpha therapy
      for advanced hepatocellular carcinoma.
AB  - We report the case of a 66-year-old man with hepatic cirrhosis and multiple
      hypervascular tumors in both lobes of the liver as well as tumor thrombi in the
      portal vein. After unresectable hepatocellular carcinoma was diagnosed,
      transcatheter arterial embolization was considered to be difficult, because he
      had major portal vein thrombosis. Conventional ultrasonically-guided local
      treatments, such as percutaneous ethanol injection therapy and radiofrequency
      ablation, were also of no value because the tumors were huge and multiple.
      Ultimately, he was treated with a combination of intraarterial 5-fluorouracil and
      intramuscular interferon-alpha. After treatment, the multiple tumors became non
      enhancing on contrast computed tomography scans and showed a marked decrease in
      size. There were no serious adverse effects (such as myelosuppression or
      hepatotoxicity) during treatment or follow-up and the patient is doing well at
      present. In conclusion, a combination of intraarterial 5-fluorouracil with
      intramuscular interferon-alpha appears to be useful for the management of
      advanced hepatocellular carcinoma, especially in patients for whom more
      aggressive treatment is not acceptable.

PMID- 14696402
TI  - Perforin and granzyme B of cytotoxic T lymphocyte mediate apoptosis irrespective
      of Helicobacter pylori infection: possible act as a trigger of peptic ulcer
      formation.
AB  - BACKGROUND/AIMS: The perforin/granzyme and Fas/Fas ligand pathways are two known
      major pathways of cytotoxic T lymphocyte-mediated apoptosis. We designed a
      clinical study to examine whether cytotoxic T lymphocyte-mediated apoptosis
      associated with peptic ulcer formation may occur via either or both of these two
      pathways. METHODOLOGY: Mucosal biopsy specimens were obtained endoscopically from
      the marginal zone of active stage gastric and duodenal ulcers in patients with or
      without Helicobacter pylori infection. RT-PCR, immunoblotting and
      immunohistochemistry were used to study the samples for the expression of
      apoptotic cells, perforin, granzyme B, Fas, Fas ligand and caspase 3. RESULTS:
      Apoptotic cells (Tunnel positive cells) appeared in the marginal zone of gastric
      and duodenal ulcers with and without H. pylori infection. Perforin/granzyme B and
      caspase 3 were expressed consistently, however Fas ligand was not. Furthermore,
      the immunohistochemical findings demonstrated apoptotic changes of target cells
      caused by perforin/granzyme B. CONCLUSIONS: These results suggest that the main
      pathway of cytotoxic T lymphocyte-mediated apoptosis in peptic ulcer formation is
      the perforin/granzyme pathway irrespective of H. pylori infection.

PMID- 14696404
TI  - Usefulness of per-rectal portal scintigraphy with technetium-99m pertechnetate
      for prognosis of primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: Conventional methods predicting survival in patients with
      primary biliary cirrhosis are based on the results of blood tests and on clinical
      condition, both of which may be affected by treatment. Portal circulation can be
      evaluated in a relatively noninvasive manner by per-rectal portal scintigraphy.
      We used this method to evaluate portal hemodynamics and assess prognosis in
      patients with primary biliary cirrhosis. METHODOLOGY: Per-rectal portal
      scintigraphy with Tc-99m pertechnetate was done in 51 patients with primary
      biliary cirrhosis. A solution containing Tc-99m pertechnetate was instilled into
      the rectum, and serial scintigrams were taken while radioactivity curves for the
      liver and heart were recorded sequentially. The per-rectal portal shunt index was
      calculated from the curves. RESULTS: The shunt index was higher in patients with
      stage IV primary biliary cirrhosis than in those with stage I, II, or III primary
      biliary cirrhosis. On the basis of portal shunt index, the patients were divided
      into those with a shunt index of less than 18%, and those with a shunt index of
      18% or more. The cumulative survival rate was lower among patients with the
      higher shunt index. On regression analysis, the portal shunt index was found to
      be significantly related to survival. CONCLUSIONS: Our results indicate that per
      rectal portal scintigraphy with Tc-99m pertechnetate can be used to non
      invasively evaluate the portal circulation of patients with primary biliary
      cirrhosis and is useful in establishing prognosis in such patients.

PMID- 14696405
TI  - Preserved function of the Oddi sphincter after endoscopic papillary balloon
      dilation.
AB  - BACKGROUND/AIMS: Endoscopic papillary balloon dilation (EPBD) is a safe and
      effective procedure for the treatment of bile duct stones that appears to be less
      hazardous to the sphincter of Oddi than endoscopic sphincterotomy. However,
      little is known about the function of Oddi muscle after EPBD. The aim of the
      present study is to evaluate Oddi muscle function using quantitative
      cholescintigraphy. METHODOLOGY: This study was conducted using 12 patients
      treated for bile duct stones by EPBD, and 8 patients treated by endoscopic
      sphincterotomy, followed by laparoscopic cholecystectomy thereafter. For the
      controls, 10 asymptomatic cholecystectomized patients were used. From 1-3 years
      after the interventional procedures, patients received a quantitative
      cholescintigraphy examination using 185 MBq of technetium-99m-N-pyridoxyl-5
      methyl-tryptophan. The hepatic hilum-duodenum transit time on quantitative
      cholescintigraphy was measured as the time interval between the initial
      appearance of isotope activity at the hepatic hilum and that at the duodenum.
      RESULTS: Mean hilum-duodenum transit time in patients after EPBD (6.3 min, 95%CI
      4.5-8.0) was not different from that in control patients (6.5 min, 95%CI 4.3
      8.7), whereas mean hilum-duodenum transit time in endoscopic sphincterotomy
      patients (3.2 min, 95%CI 2.4-4.0) was markedly shorter than both the control and
      EPBD groups (p = 0.0053). CONCLUSIONS: The function of the sphincter of Oddi may
      be preserved after endoscopic papillary balloon dilation.

PMID- 14696406
TI  - Prevalence of gallstone disease in patients with end-stage renal disease treated
      with hemodialysis in Korea.
AB  - BACKGROUND/AIMS: Gallstone disease is one of the major causes of morbidity in
      adults. Hemodialysis has been found to increase the risk of gallstone formation
      secondary to increased biliary cholesterol and biliary saturation index. However,
      there is very little data on the prevalence of gallstones in hemodialysis
      patients. METHODOLOGY: We compared the prevalence of gallstone disease in
      patients with end-stage renal disease treated with hemodialysis with that of 208
      age- and sex-matched controls (non-uremic group). Patients who had chronic liver
      disease, renal disease, and diabetes were excluded from the control group.
      RESULTS: In our study, we found a prevalence for gallstone of 18.2% in patients
      with end-stage renal disease treated with hemodialysis, which was significantly
      higher than 5.3% in the non-uremic control. Most of our hemodialysis patients had
      asymptomatic cholecystolithiasis. Hemodialysis patients with cholecystolithiasis
      were significantly older than patients without gallstones. We did not find a
      difference in sex and duration of hemodialysis treatment between patients with
      and without gallstones. CONCLUSIONS: Our results suggest that the prevalence of
      gallstone disease is higher in patients with end-stage renal disease treated with
      hemodialysis than in the non-uremic population in Korea.

PMID- 14696407
TI  - Risk factors for acute pancreatitis after endoscopic papillary balloon dilation.
AB  - BACKGROUND/AIMS: Although EPBD (endoscopic papillary balloon dilation) may cause
      acute pancreatitis, risk factors for post-EPBD pancreatitis have not been well
      described. We retrospectively analyzed risk factors predictive of acute
      pancreatitis after EPBD. METHODOLOGY: A total of 101 patients underwent EPBD for
      choledocholithiasis. Post-EPBD acute pancreatitis was investigated. Nineteen
      potential risk factors, related to clinical characteristics or procedures, were
      retrospectively analyzed univariately and multivariately. RESULTS: Bile duct
      clearance was achieved in 96 patients. Serum amylase was elevated after EPBD in
      69 patients. Early complications occurred in 11 patients (11%); 5 had minimal
      (pain persisting for only 12-24 hours) and 6 mild (requiring 1-3 days of
      treatment) pancreatitis. These 11 patients showed at least a three-fold elevation
      of serum amylase. Multivariate analysis identified two independent risk factors
      for pancreatitis (prior history of acute pancreatitis, and bile duct diameter <
      or = 9 mm). The risk for post-EPBD pancreatitis was not associated with young
      age, pre-EPBD hyperamylasemia, large or multiple stones, periampullary
      diverticulum, pancreatic contrast injection, mechanical lithotripsy or residual
      stones. CONCLUSIONS: Acute pancreatitis, usually mild or minimal, can be
      anticipated after EPBD for bile duct stones in approximately 10% of patients. In
      those with previous pancreatitis or a non-dilated bile duct, special care is
      necessary given the high incidence of pancreatitis.

PMID- 14696408
TI  - Evaluation of BAT-26 as an indicator of microsatellite instability in gallbladder
      carcinomas.
AB  - BACKGROUND/AIMS: The genetic pathways of gallbladder cancer are not yet well
      defined, since the contribution of genetic abnormalities, clarified in other
      organs, remains questionable. Our aim was to evaluate the role of microsatellite
      instability in this organs carcinogenesis. METHODOLOGY: We investigated a group
      of 20 gallbladder carcinomas from Greek patients with regard to alterations in
      length of the BAT-26 mononucleotide marker--as an indicator of microsatellite
      instability. The findings were correlated with the presence of p53 and ras
      mutations, alterations of the bax and TGF-beta RII genes and tumors'
      clinicopathological features. Polymerase chain reaction and electrophoretic
      analysis in a non-denaturating 25% polyacrylamide gel was performed for the
      detection of BAT-26 size variations. RESULTS: None of our specimens showed
      microsatellite instability at the BAT-26 marker. CONCLUSIONS: BAT-26, an
      indicator of high-level microsatellite instability, may not be sufficient, when
      used alone, for determining the microsatellite instability status of gallbladder
      carcinomas, since these may be characterized by low-level instability. Bax and
      TGF-beta RII genes may not also be targets of instability in this type of tumors.

PMID- 14696409
TI  - Evaluation of hepatic functions and biliary dynamics in patients with liver
      cirrhosis by quantitative scintigraphy.
AB  - BACKGROUND/AIMS: Aim of the study is to determine the changes in hepatocyte and
      gallbladder motor functions, and biliary dynamics in patients with liver
      cirrhosis. METHODOLOGY: The study group consisted of 17 patients with liver
      cirrhosis (12 males, 5 females) who were diagnosed by clinical, laboratory and
      histopathologic findings. Control group consisted of 20 healthy persons (14
      males, 6 females). Quantitative hepatobiliary scintigraphy was performed by using
      Tc99m-Mebrofenin i.v. and dynamic images were obtained and evaluated
      quantitatively by computer. Maximum excretion time of radiodiagnostic agent by
      liver (Tmax) and half excretion time of radio-diagnostic agent from liver (T
      1/2), gallbladder filling time, gallbladder ejection fraction and the transit
      time of bile to duodenum were determined. RESULTS: Mean values of Tmax was 25.76
      vs. 12.40 min, T 1/2 was 37.55 vs. 23.15 min, gallbladder filling time was 53.35
      vs. 30.57 min, and transit time of bile to duodenum was 39.88 vs. 25.00 min in
      the patients and control group, respectively. These values increased
      significantly in the patient group (p < 0.05) compared to controls. Mean
      gallbladder ejection fraction was 37.55% in the patient group and 41.84% in the
      control group without any statistical significance (p > 0.05). The incidence of
      gallbladder stone was 29.41% in the cirrhosis group and 5% in the control group
      (p < 0.05). CONCLUSIONS: The quantitative hepatobiliary scintigraphy is a simple
      and reliable method in evaluation of hepatic functions and biliary dynamics in
      cirrhotic patients. Although the incidence of gallbladder stone is significantly
      increased in cirrhotic patients, it seems that a stone in the gallbladder does
      not affect the gallbladder motor functions.

PMID- 14696410
TI  - A retrospective analysis of patients with gallbladder cancer treated with radical
      resection versus cholecystectomy plus external radiotherapy.
AB  - BACKGROUND/AIMS: To compare patients with gallbladder cancer treated with radical
      resection and regional lymphadenectomy (RR-RL) versus simple cholecystectomy and
      adjuvant external radiotherapy (SC-ERT) and determine outcome. METHODOLOGY:
      Presentation, operative data, complications and survival were examined in 137
      patients. In particular, the 45 patients treated with RR-RL or SC-ERT. RESULTS:
      Twenty-five had SC-ERT and 20 had a RR-RL. There were no epidemiological
      differences between groups. Resection of segments IV-b and V and en bloc
      dissection of regional lymph nodes was the most frequently used procedure (75%).
      The morbidity and mortality of the radical procedure were 25% and 10%. The
      morbidity of SC-ERT was 16%. All patients with Nevin I are alive. For lesions
      Nevin II and Nevin III RR-RL offered a 100% 5-year survival rate and SC-ERT had a
      62% and 39% 5-year survival rate respectively. For lesions Nevin IV and V there
      was no difference in long-term survival. CONCLUSIONS: RR-RL is better than SC-ERT
      in patients with Nevin II and III lesions because it improves survival rate. SC
      ERT can be recommended as an alternative treatment. For more advanced lesions
      further trials are needed.

PMID- 14696411
TI  - Quantitative analysis of ductus proliferation, proliferative activity, Kupffer
      cell proliferation and angiogenesis in differential diagnosis of biliary atresia
      and neonatal hepatitis.
AB  - BACKGROUND/AIMS: The clinical presentation of cholestasis in infancy caused by
      neonatal hepatitis and biliary atresia are very similar. Differential diagnosis
      is sometimes very difficult. The diagnostic accuracy is very important. The
      surgical treatment of biliary atresia should be performed as early as possible.
      If cases of biliary atresia are misdiagnosed, they will become progressive
      cirrhosis and if cases of neonatal hepatitis are misdiagnosed, they will result
      in unnecessary laparotomy. The aim of this study is to determine the role of
      quantitative analysis of ductus proliferation, proliferative activity, Kupffer
      cell proliferation and angiogenesis in the differential diagnosis of biliary
      atresia and neonatal hepatitis. METHODOLOGY: This study included 60 infants, 30
      with neonatal hepatitis and 30 with biliary atresia. Differential diagnosis was
      done by ultrasonography, cholescintigraphy and liver biopsy. The parafifin
      embedded tissue sections of liver biopsies underwent immunohistochemistry with
      Ki67 to mark proliferation activity, cytokeratin to mark the proliferating
      ductuli, vimentin to mark Kupffer cells, and CD34 to mark capillary vessels.
      Number of ductuli per high power field, number of Ki-67 positive cells per
      ductus, number of Kupffer cells per high power field and number of capillary
      vessels per high power field were calculated. Independent T test was used for
      statistical evaluation. RESULTS: Independent sample T test indicated that there
      is a significant difference for proliferating ductuli and proliferation activity
      between neonatal hepatitis and biliary atresia. Biliary atresia cases represent
      more proliferating ductuli and proliferation activity in ductal epithelial cells
      than neonatal hepatitis cases. There is no statistical significance for Kupffer
      cell proliferation and vascularization. CONCLUSIONS: Our results indicate that,
      quantitative analysis of proliferating ductuli and proliferation activity of
      ductal epithelial cells may be helpful in differential diagnosis of neonatal
      hepatitis and biliary atresia. Besides neither Kupffer cell proliferation nor
      vascularization are found to be useful in differential diagnosis.

PMID- 14696412
TI  - Coronary artery disease and upper abdominal surgery: impact of anesthesia on
      perioperative myocardial ischemia.
AB  - BACKGROUND/AIMS: Some papers claim that epidural anesthesia and analgesia lowers
      the incidence of perioperative ischemic events and may have a favorable effect on
      perioperative cardiac morbidity and mortality. We studied the effect of epidural
      anesthesia and analgesia on perioperative myocardial ischemia, in a group of
      patients with known coronary artery disease, who underwent upper abdominal
      surgery. METHODOLOGY: Fifty patients with coronary artery disease scheduled for
      elective upper abdominal surgery, were randomized to two study groups: Group A (n
      = 25) received general anesthesia plus epidural anesthesia and analgesia, while
      group B (n = 25) received general anesthesia with postoperative i.v. analgesia.
      All patients had Holter ECG recording from 24 hours preoperatively until 48 hours
      postoperatively. RESULTS: Preoperatively, no significant differences in ischemic
      burden were observed between the two groups. Intraoperatively, significantly
      fewer patients in group A had ischemic episodes (8% vs. 36%, p < 0.05) and there
      was also a significant reduction in the number of ischemic episodes and in mean
      duration of ischemia per hour of monitoring. Similar findings were observed in
      the first 24 hours postoperatively but not later on, with 12% of patients in
      group A having ischemic episodes vs. 60% in group B (p < 0.01). Group A had
      significantly better pain control postoperatively. Only one third of ischemic
      episodes were related to hemodynamic abnormality, and most of them were
      clinically silent. No serious cardiac morbidity or mortality was observed during
      the period of monitoring. CONCLUSIONS: Epidural anesthesia and analgesia reduces
      intraoperative and early postoperative ischemia in patients with known coronary
      artery disease undergoing upper abdominal surgery.

PMID- 14696413
TI  - Microbiology difference between colonized catheters and catheter-related
      bloodstream infections.
AB  - BACKGROUND/AIMS: Central vein catheters for patients receiving total parenteral
      nutrition have a high incidence of colonized catheters and catheter-related
      bloodstream infections. However, the actual incidence and bacterial pattern have
      not been well studied. This study was undertaken to investigate the difference in
      bacteriology between colonized catheters and catheter-related bloodstream
      infections. METHODOLOGY: From January 1997 to March 1998, 354 patients receiving
      total parenteral nutrition were included in this study. The patients ranged in
      age from 49 to 80 years, 151 women and 203 men. Colonized catheters and catheter
      related bloodstream infections were defined. RESULTS: The culture was performed
      in 249 catheter tips (249 of 614, 40.6%). Sixty tips were found to have
      organisms. The organisms cultured from colonized catheters were Gram(+) aerobic
      bacteria (34, 56.7%), fungi (14, 23.3%), and Gram(-) aerobic bacteria (12, 20%).
      The organisms cultured from catheter-related bloodstream infections were fungi
      (16, 64%), Gram(-) aerobic bacteria (5, 20%), and Gram(+) aerobic bacteria (4,
      16%). Dermatogenic infection in colonized catheters should be stressed, but
      systemic fungal infection in catheter-related bloodstream infections should be
      emphasized. CONCLUSIONS: A striking difference exists in bacterial species
      between colonized catheters and catheter-related bloodstream infections. Further
      studies on different treatment strategy for colonized catheters and catheter
      related bloodstream infections should be undertaken. The combined approach of a
      total parenteral nutrition team, sterile protocols, and early diagnosis of
      fungemia should be advocated for the total parenteral nutrition patients.

PMID- 14696414
TI  - Doppler ultrasonography for postoperative hepatofugal portal blood flow of the
      intrahepatic portal vein.
AB  - BACKGROUND/AIMS: The clinical significance of the hepatofugal portal blood flow
      after abdominal surgery involving other than portosystemic shunt was investigated
      in our hepatobiliary pancreatic surgical division. METHODOLOGY: Preoperative and
      postoperative Color and pulsed Doppler ultrasonography was performed on 101
      consecutive patients who underwent abdominal surgery. Preoperative Doppler
      ultrasonography was performed within one week before surgery. Basically,
      postoperative Doppler ultrasonography was performed every other day within one
      week after surgery and once a week 2 weeks after surgery. The portal flow
      direction was assessed in the right portal branch or the umbilical portion of the
      left portal branch. RESULTS: Of the 101 patients, 9 showed a hepatofugal flow in
      the intrahepatic portal vein, 5 of which showed a total hepatofugal flow, and 4
      of these 5 patients died of hepatic failure. The remaining 4 patients showed a
      partial hepatofugal flow and postoperative hyperbilirubinemia, but all 4
      survived. CONCLUSIONS: Postoperative total hepatofugal flow indicated a serious
      prognostic sign of critical liver damage. Postoperative partial hepatofugal flow
      induced postoperative hyperbilirubinemia which was not critical.

PMID- 14696415
TI  - Does colitis associated with primary sclerosing cholangitis represent an actual
      subset of ulcerative colitis?
AB  - BACKGROUND/AIMS: The clinical course and endoscopic features of colitis
      associated with primary sclerosing cholangitis have not been well documented.
      METHODOLOGY: Since 1980, a total of 485 patients with ulcerative colitis have
      been seen in our departments. During this period, we experienced 6 patients with
      primary sclerosing cholangitis, 4 of whom had ulcerative colitis concomitantly.
      RESULTS: Colitis preceded primary sclerosing cholangitis in 3 of the 4 patients.
      There were 2 males and 2 females. One patient had left-sided colitis while 3 had
      total colitis, 1 with a first attack and 3 with relapsing-remitting type. Two of
      the 4 patients had colonoscopically dominant inflammation in the proximal colon
      with continuous histological inflammation from the rectum to the proximal colon.
      Three colitic patients have been well controlled with oral sulfasalzine or
      mesalazine administration. Only 1 female patient had been hospitalized twice for
      moderately severe attacks of ulcerative colitis that required systemic
      prednisolone administration, however, this patient quickly responded to this
      treatment for each admission. CONCLUSIONS: Colitis associated with primary
      sclerosing cholangitis exhibited atypical colonoscopic findings and exhibited
      milder disease activity than ulcerative colitis without primary sclerosing
      cholangitis.

PMID- 14696417
TI  - Adenovirus expressing p27KIP1 induces apoptosis against cholangiocarcinoma cells
      by triggering Fas ligand on the cell surface.
AB  - BACKGROUND/AIMS: The prognosis of patients with cholangiocarcinoma is poor
      because of the difficulty of surgical curative resection. Therefore, other
      effective treatments must be developed especially those involving gene therapy.
      p27kip1, one of the cyclin-dependent kinase inhibitors, is known to limit
      proliferation of the cells. Our previous reports have shown that the
      overexpression of p27kip1 by a recombinant adenoviral vector expressing p27kip1
      (Adp27) induces apoptosis. However, the mechanism of the Adp27-mediated apoptosis
      is not still resolved. Activation of the Fas pathway is one of the important
      gates for apoptosis. In this report, we examined whether p27kip1-induced
      apoptosis is closely related to the Fas/Fas ligand (FasL) system. RESULTS: After
      infection of Adp27, flow cytometric analysis showed that Fas ligand was expressed
      on the cell surface of cholangiocarcinoma cell lines (TFK-1). In spite of
      detecting the cell surface expression of Fas ligand, overexpression of p27kip1
      increased no amount of Fas ligand in mRNA by quantitative RT-PCR and protein
      level by Western blot. In addition, the immunocytochemical analysis showed that
      Fas ligand was adequately stored within the cytosol of TFK-1 cells. More
      interestingly, Adp27-induced apoptosis was completely inhibited by the
      neutralizing antibody of Fas ligand (NOK-1). This result suggests that
      overexpression of p27kip1 may deliver Fas ligand to the cell surface and mainly
      utilizes the Fas pathway as a gate of apoptosis. CONCLUSIONS: This is the first
      report to prove that Adp27-mediated apoptosis utilizes the Fas pathway by
      delivering Fas ligand to the cell surface.

PMID- 14696416
TI  - Colorectal cancer metastases: surgical indications and multimodal approach.
AB  - BACKGROUND/AIMS: The therapeutic plan to follow in patients affected by hepatic
      and pulmonary metastases from colorectal cancer is based on prognostic factors
      and staging. METHODOLOGY: Our experience from January 1980 to January 2002
      underlines the effectiveness of combined multimodal therapy in the treatment of
      advanced metastatic stages. A total of 224 patients with metastases from
      colorectal cancer have been treated. Among these patients 160 underwent surgery
      (4 pulmonary and 156 hepatic resections), 17 have been reoperated for metastatic
      relapse, 14 with multiple metastases underwent locoregional therapy, while 33,
      deemed not resectable initially, have been treated with neoadjuvant chemo- and
      radio-therapy. RESULTS: For the operated patient group the 5-year actuarial
      survival was 22% with an operative morbidity of 17.5% and mortality of 3.8%. The
      17 patients reoperated for metastatic relapse had a 5-year actuarial survival of
      21% with an operative morbidity of 11.6% and mortality of 5.8%. The 14 patients
      treated with locoregional therapy had a median survival of 6 months whereas the
      33 patients treated with combined multimodal treatment in two different periods
      had a response rate of 57.57%. Five patients had a complete response and 4 are
      presently alive: 3 are disease free and 1 with disease. 1 died of pulmonary
      primitive neoplasm 24 months later. CONCLUSIONS: Surgical resection is presently
      the best known treatment for metastatic disease. In advanced, but not yet
      disseminated, stages in which there is no indication to surgery on metastases (II
      III stages according to Gennari's classification), a neoadjuvant treatment is
      proposed, if the primary tumor has already been completely resected. This
      therapeutic strategy, called combined multimodal therapy, has the aim to obtain
      the disease regression and to offer the chance of disease re-staging.

PMID- 14696418
TI  - Brain death-induced expression of ICAM-1 and VCAM-1 on rat hepatocytes.
AB  - BACKGROUND/AIMS: Brain death is a significant risk factor for donor organs used
      for transplantation. Adhesion molecules, ICAM-1 and VCAM-1 are induced in the
      liver of brain-dead patients, which have important roles in allograft rejection.
      However, the role of these molecules on hepatocytes has not been investigated. To
      investigate morphological changes and expression of ICAM-1 and VCAM-1 on
      hepatocytes, we employed a standardized rat model of brain death. METHODOLOGY:
      Isolated hepatocytes were examined by histology and immunohistology. RESULTS: The
      hepatocytes of brain-dead rats were less stained with eosin indicating the
      decreased permeability and impaired integrity of the cell membranes.
      Immunohistologically, expression of ICAM-1 was weak on hepatocytes of normal
      rats, and clearly enhanced and after brain death. Similarly, expression of VCAM-1
      was not identified in the normal, but strongly induced after brain death.
      CONCLUSIONS: These findings indicate the increased immunogenicity of donor
      hepatocytes after brain death. Immunomodulation before engraftment of cellular
      grafts to diminish or decrease the immunogenicity may result in better outcome of
      hepatocytes from brain-dead donor.

PMID- 14696420
TI  - Induction of apoptosis and inhibition of growth of human hepatoma HepG2 cells by
      heparin.
AB  - BACKGROUND/AIMS: Apoptotic and anti-proliferative effects of heparin on a number
      of cancers have been described. There have been no studies analyzing the effect
      of heparin on human hepatoma cells. The aim of this study was to investigate the
      effect of heparin on human hepatoma cell line, HepG2. METHODOLOGY: HepG2 cell
      line was cultured with different concentrations of heparin. Colony count,
      viability assay, percentage of the apoptosis and proliferative index were
      assessed at the end of the 7th day. Trypan blue was used to assess viability.
      Apoptosis and proliferative indexes were assessed by flow-cytometry. RESULTS:
      Hepatoma cells were arrested at the G0/G1 phase with heparin incubation and
      proliferative indexes decreased significantly in 20, 40 and 80 U/mL of heparin
      concentrations in comparison with the control (36 +/- 1%, 30 +/- 5% and 29 +/- 8%
      vs. 44 +/- 1%, p < 0.01). Flow cytometry revealed a statistically significant
      increase in apoptosis in groups incubated with 40 and 80 U/mL of heparin in
      comparison with the control (39 +/- 26% and 58 +/- 18% vs. 0.83 +/- 1.3%, p <
      0.01). Colony counts per well and viable cells per microL decreased significantly
      in 80 U/mL of heparin. CONCLUSIONS: Heparin leads to a significant anti
      proliferative and an apoptotic effect on human hepatoma cells in vitro.

PMID- 14696419
TI  - Chromosome arm 20q gains and other genomic alterations in esophageal squamous
      cell carcinoma, as analyzed by comparative genomic hybridization and fluorescence
      in situ hybridization.
AB  - BACKGROUND/AIMS: Our recent analysis of gastric cancers and colorectal cancers
      using comparative genomic hybridization revealed a novel, high frequent copy
      number increases the long arm of chromosome 20 in association with possible
      involvement of liver metastases and poor prognosis. This led to further
      comparative genomic hybridization analysis of chromosomal aberrations in primary
      tumors of esophageal squamous cell carcinoma. The aim of the study presented here
      was to analyze the chromosomal aberrations and to determine the numbers of copies
      of AIB1, BTAK, DcR3 and E2F1 as putative target genes on chromosome 20q as well
      as their expression and relation to clinicopathological features in 41 primary
      tumors of esophageal squamous cell carcinoma. METHODOLOGY: We used comparative
      genomic hybridization to screen 41 primary tumors of esophageal squamous cell
      carcinoma for changes in the number of copies of DNA sequences. To further
      characterize the gain of DNA sequences at 20q, we also performed fluorescence in
      situ hybridization analysis. We examined the relationship between these changes
      and clinicopathological factors. RESULTS: Gains in chromosome arm 20q were
      detected (34.1%) as well as a high level of gain in 20q12-13 (4.8%). AIB1
      amplification was observed in 4.9% (2/41), BTAK amplification in 9.8% (4/41),
      DcR3 amplification was in 4.9% (2/41), and E2F1 amplification in 7.3% (3/41). The
      survival of patients with BTAK or E2F1 amplification was significantly lower than
      that of patients without these abnormalities. CONCLUSIONS: These findings provide
      evidence for a number of previously unknown genomic aberrations in esophageal
      squamous cell carcinoma, suggesting the existence of target regions relevant to
      its progression. Esophageal squamous cell carcinoma with 20q gain showed
      extensive lung metastases, pleural effusion and liver metastases and poorer
      prognosis compared to cases without 20q gain. Our results suggest that
      amplification of BTAK or E2F1 are likely to lead to an increase in the number of
      malignant phenotypes of esophageal squamous cell carcinoma and that these
      aberrations can be expected to be useful as markers of poor prognosis.

PMID- 14696421
TI  - Usefulness of contrast-enhanced ultrasonography with dynamic flow imaging to
      evaluate therapeutic effects for hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: To examine the usefulness of dynamic flow imaging in identifying
      the therapeutic effects for hepatocellular carcinoma, we performed contrast
      enhanced ultrasonography with Levovist. METHODOLOGY: Tumor vascularity of 48
      hepatocellular carcinoma nodules in 27 patients infected with hepatitis C virus
      was assessed before and after radiofrequency ablation therapy by dynamic flow
      imaging with a wide-band power Doppler technology. RESULTS: All patients showed
      hypervascular enhancement of hepatocellular carcinoma on contrast-enhanced
      ultrasonography and/or dynamic computed tomography. The dynamic flow was obtained
      as vascular and perfusion images of hepatic tumors. The diameters of tumors were
      1.1-2.0 cm in 12 nodules, 2.1-3.0 cm in 28, and 3.1-5.0 cm in 8, respectively. We
      were able to assess the tumor vascularities in 45 of 48 nodules before
      radiofrequency ablation by the dynamic flow. Three nodules showed insufficient
      dynamic flow which was located approximately 9 cm in depth from the body surface.
      The dynamic flow study for the therapeutic efficacy indicated that the tumor
      vessels disappeared in 43 of the 45 visible nodules. The tumor vascularities were
      noted in the remaining 2 nodules, and they were successfully retreated by
      radiofrequency ablation. The frequencies detecting positive enhancement in
      pretreatment and post-treatment were almost equivalent between vascular phase of
      dynamic flow on ultrasonography and early phase on helical dynamic computed
      tomography, although 5 nodules gave different findings; 2 were positive only on
      ultrasonography, and 3 were positive only on computed tomography. A major
      complication of radiofrequency ablation procedure was noted in only one case
      associated with intestinal edema, but it was cured by medical treatment.
      CONCLUSIONS: The results indicated that contrast-enhanced dynamic flow imaging on
      ultrasonography is a reliable tool to evaluate intratumoral vascularity both
      before and after radiofrequency ablation treatment in patients with
      hepatocellular carcinoma.

PMID- 14696422
TI  - Trends in clinical characteristics, treatment and prognosis of hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: This study was undertaken to evaluate the serial changes of
      various factors in patients with hepatocellular carcinoma, including hepatitis
      viruses, age distribution, female-to-male ratio, size and the number of
      hepatocellular carcinoma tumors at initial detection, the types of treatment and
      survival during a 12-year period. METHODOLOGY: Seven hundred and four consecutive
      patients with hepatocellular carcinoma lesions observed from Jan 1989 to Dec 2000
      (12 years) at the Internal Medicine Department, Saga Prefectural Hospital
      Koseikan were retrospectively enrolled in the study. The follow-up period was
      divided into four terms as follows: 1989-91, 1992-94, 1995-97 and 1998-2000. The
      serial changes of causal hepatitis viruses, age distribution, gender ratio, tumor
      size, the number of hepatocellular carcinoma tumors at initial detection, the
      types of treatment and survival were analyzed and compared among the four
      different terms. RESULTS: Regarding viral markers, the association of an HCV
      infection has become more predominant in hepatocellular carcinoma cases, while
      the ratio of hepatocellular carcinoma patients infected with HBV has decreased
      during this 12-year period. In addition, the rate of hepatocellular carcinoma
      measuring 3 cm or less in diameter or solitary hepatocellular carcinoma at
      initial detection has increased during the 12-year period. The female-to-male
      ratio has increased from 33.6% in 1989-1991, 34.8% in 1992-1994, 48.7% in 1995
      1997 to 60.6% in 1998-2000, respectively. Due to increased early detection, the
      types of treatment for hepatocellular carcinoma have shifted from arterial
      interventional therapy to local ablation therapy combined with or without
      interventional therapy. Therefore, although the age distribution of all 704
      hepatocellular carcinoma patients has shifted to slightly older ages as shown by
      the ages of 64.1 years old, 63.4 years old, 66.6 years old and 67.3 years old in
      the four terms, respectively, the survival of the patients with hepatocellular
      carcinoma proved to had become significantly longer than before during the 12
      year period. CONCLUSIONS: Hepatocellular carcinoma patients tended to show an
      increased prevalence of HCV, a higher age distribution, an increasing female
      prevalence, an earlier detection, advanced multidisciplinary therapies and
      prolonged survival in the last 12 years.

PMID- 14696423
TI  - Stapled hemorrhoidectomy: surgical notes and results.
AB  - Recently the surgical treatment of hemorrhoids using a circular stapler device
      has gained increasing approval. The Longo's procedure reduces the rectal mucosal
      and hemorrhoid prolapse using a circular stapler to resect transversally a
      mucosal-submucosal rectal ring in order to restore the correct anatomical
      relationships of the anal canal structures. The recent availability of a
      dedicated instrument kit (PPH01 Ethicon Endo-Surgery) allowed an easy diffusion
      of this technique. From March 1999 to September 2001, 198 patients with III-IV
      degree hemorrhoids were treated by a single expert surgeon using the dedicated
      kit instrumentation (PPH01) according to the Longo's technique, adopting some
      variations from the original procedure: 1) The anal dilator is not fixed to the
      perianal skin with forceps or stitches but is kept by the assistant. 2) In
      performing the purse-string suture particular care must be given to the
      apposition of the stitches at the same level also in the posterolateral side
      where there is a natural trend to apply the stitches at a lower level;
      furthermore the last stitch of the purse-string suture must be overlapped to the
      first one in order to allow a better hemostasis when the knot is tightened. 3)
      After having performed the purse-string and having resected the mucosa and
      submucosa, an accurate hemostasis with U-shaped 3/0 vicryl stitches firmly
      reduces the postoperative bleeding. We recorded pain scores, short- and long-term
      complications (included moderate-severe pain, persistent pain), recurrences and
      postoperative hospital stay. The data of the last 40 consecutive patients who
      underwent stapled hemorrhoidectomy were compared with the data obtained by 40
      consecutive patients who underwent Milligan-Morgan diathermic hemorrhoidectomy
      for III-IV degree non-circumferential hemorrhoids by the same surgeon. In the 198
      stapled hemorrhoidectomy cases the rate of postoperative moderate-severe pain and
      persistent pain were 6% and 2.5% respectively, the rate of short-term and long
      term bleeding were 4.5% and 3.5%, the recurrence rate was 2.5%. The mean
      postoperative stay was 1.6 days. The stapled group had significantly lower
      postoperative moderate-severe pain, bleeding and soiling than the Milligan-Morgan
      group.

PMID- 14696424
TI  - Bile duct carcinoma arising in metaplastic biliary epithelium of the intestinal
      type: a case report.
AB  - We report herein a case of distal bile duct carcinoma showing intestinal
      differentiation diagnosed 3 years after endoscopic sphincterotomy for
      choledocholithiasis. The diagnostic problem in this case was that the granular
      mucosa, which is a typical finding of superficial mucosal extension of bile duct
      carcinoma in general, was interpreted as hyperplasia accompanying metaplasia in
      cholangioscopic biopsy. Discrimination of superficial mucosal cancer extension
      from hyperplastic mucosa with metaplastic changes was impossible using
      cholangioscopic examination. In our case, reflux and stasis of the duodenal and
      pancreatic juice into the biliary tract might have occurred because of abnormal
      function of the papilla of Vater following endoscopic sphincterotomy. It might be
      suggested that endoscopic sphincterotomy contributed to the metaplastic changes
      in the bile duct mucosa in our case.

PMID- 14696425
TI  - Fibrolamellar hepatocellular carcinoma: report of a case.
AB  - We report a case of fibrolamellar hepatocellular carcinoma, which occurred in a
      58-year-old man with normal liver function. Preoperative ultrasonography,
      computed tomography and magnetic resonance imaging depicted a large tumor in the
      left lateral segment, which was compatible with the typical radiological features
      of fibrolamellar hepatocellular carcinoma. He underwent left lobectomy and no
      lymphadenopathy or distant metastasis was demonstrated. Macroscopic findings of
      the resected liver demonstrated a well-defined whitish-yellow tumor with a
      central scar. Microscopic findings of the tumor showed cords of tumor cells,
      which were surrounded by abundant collagenous fibrous tissue arranged in a
      lamellar distribution. He has been doing well for approximately one year since
      the surgery without any signs of recurrence. In addition, we discuss the
      clinicopathological features of fibrolamellar hepatocellular carcinoma based on a
      review of 22 Japanese patients who have been previously reported.

PMID- 14696426
TI  - Liver resection for intrahepatic lithiasis. Report of a case.
AB  - Intrahepatic primary lithiasis is extremely rare in the Western world. The
      development of endoscopic technique permitted a conservative treatment for this
      disease. Because of the high recurrence rate after conservative treatment due to
      the remaining biliary stricture and the risk of incidental cholangiocarcinoma, we
      believe that hepatic resection is the treatment of choice of unilateral liver
      intrahepatic primary lithiasis. Herein we present a case affected with
      intrahepatic primary lithiasis localized into the left biliary system that
      successfully underwent left hepatic lobectomy.

PMID- 14696427
TI  - Conversion from external nasobiliary drainage to internal drainage using
      endoscopically available scissor forceps.
AB  - Endoscopic nasobiliary drainage may cause undue stress, such as pharyngeal
      discomfort. We converted external drainage to internal drainage by cutting the
      external drainage tube with endoscopically available scissor forceps. Endoscopic
      nasobiliary drainage tubes were cut in the vicinity of the papilla using scissor
      forceps in 4 patients. The drainage tube was successfully cut in all patients.
      The tube was left for short-term internal drainage in 3 patients until the
      operation or endoscopic treatment was performed. The remaining patient with
      pancreatic head cancer was followed as an outpatient and the tube stent was
      occluded 62 days after cutting. Although further studies using a larger number of
      patients are needed, our procedure is thought to be beneficial to patients
      undergoing endoscopic nasobiliary drainage.

PMID- 14696428
TI  - Resection of localized recurrences after hepatectomy of colorectal cancer
      metastases.
AB  - BACKGROUND/AIMS: Hepatectomy is generally considered the only mode of curative
      treatment available for patients with colorectal liver metastases, even though
      recurrence occurs in more than 60% of the patients. METHODOLOGY: This is a
      retrospective study examining the survival of 11 patients undergoing surgical
      excision of recurrences gained from 46 patients undergoing initial hepatectomy
      for metastatic colorectal cancer. These 46 patients had curative hepatectomy and
      no extrahepatic metastasis. RESULTS: Cancer recurred in 29 of the 46 patients
      after a median follow-up time of 29.5 months (range 2-183 months), and 11 had
      curative resection of localized recurrences. In 6 patients, the liver was the
      only site of recurrence and 4 patients had isolated lung metastases. One patient
      had liver and lung metastases. There was no perioperative mortality. The median
      survival time and cumulative 5-year survival rate for 11 patients after the
      repeated resection were 28 months and 43.8%, respectively. These results were
      comparable to the survival for 46 patients after the initial hepatectomy, in
      which the median survival was 29.5 months and the 5-year survival rate was 49.0%.
      CONCLUSIONS: In appropriately selected patients with colorectal cancer, surgical
      excision of localized recurrences after hepatectomy may be effective in
      prolonging survival.

PMID- 14696429
TI  - Long-term outcome of anastomosis leakage after curative resection for mid and low
      rectal cancer.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the relationship of the
      disease recurrence and prognosis of rectal cancer with anastomosis leakage after
      curative low anterior resection. METHODOLOGY: The records of 566 patients with
      primary rectal adenocarcinoma in the Veterans General Hospital-Taipei, Taiwan
      between 1991 and 1997 were reviewed. Patients who did not have anastomosis
      (abdominoperineal resection 72, Hartmann's operation 15), did not have curative
      resection (62) or expired within 30 days after operation (11) were excluded from
      the study. Another 34 patients were excluded because they did not visit our
      clinic or could not be reached by telephone or questionnaire after operation. 372
      patients who received restorative curative resection with a colorectal
      anastomosis were analyzed. The product-limit method (Kaplan-Meier) and Cox
      proportional hazard model were used to analyze survival rate and tumor
      recurrence. RESULTS: Twenty-five out of the 406 patients had anastomosis leakage
      after the operation. The 5-year disease-free, local recurrence-free survival of
      the leakage group (32.5%, 58.7%) was significantly lower than that of the non
      leakage group (71%, 88.3%). The multivariate analysis showed TNM staging (p =
      0.0001) and histological differentiation (p = 0.0002) were associated with
      overall tumor recurrence. The factors affected local tumor recurrence were TNM
      staging (p = 0.006) and anastomosis leakage (p = 0.014). CONCLUSIONS: These
      results suggested that anastomotic leakage after curative rectal surgery is
      associated with the local tumor recurrence-free survival rate even after
      adjusting for stage.

PMID- 14696430
TI  - Innovative chemotherapies for stage III colon cancer: a cost-effectiveness study.
AB  - BACKGROUND/AIMS: The lower mortality rate associated with Oxaliplatin or
      Irinotecan added to Fluorouracil chemotherapy for stage III colon cancer should
      outweigh significantly higher costs of these therapies. While efficacy data
      currently are lacking, our aim was to generate cost-effectiveness data about a
      range of potential benefits to define the increase in mortality reduction
      required for the future acceptance of these new chemotherapies. METHODOLOGY:
      Estimates of efficacy were derived from the literature. Forty-seven of our
      patients treated with Oxaliplatin or Fluorouracil/Leucovorin alone were evaluated
      for cost-analysis. RESULTS: Three scenarios for Oxaliplatin chemotherapies were
      constructed with a 20% to 50% increase of mortality reduction at 5 years after
      surgery when compared to Fluorouracil chemotherapy. The associated increase of
      cost-effectiveness ratio to Fluorouacil chemotherapy was 92% to 36%. A
      sensitivity analysis for various key input parameters demonstrated the robustness
      of the model overall. Only the choice of another chemotherapy schedule may
      significantly alter cost-effective ratios (p < 0.001). CONCLUSIONS: Even the most
      conservative scenario showed a discounted cost-effectiveness ratio of only 12,485
      per life year gained, when compared to best supportive care and therefore met
      strict cost-effectiveness standards. Oxaliplatin chemotherapy should be accepted
      for all patients with stage III colon cancer if the required 20% increase in
      mortality reduction is achieved. Because of the high impact on cost-effectiveness
      each more expensive chemo-therapy schedule with higher overall dosage should
      first prove its superior clinical efficacy.

PMID- 14696431
TI  - Significance of inflammatory cytokines in the progression of colorectal cancer.
AB  - BACKGROUND/AIMS: Circulating levels of inflammatory cytokines are associated with
      the disease status of cancer patients. Our purpose was to determine whether the
      profile of serum levels of interleukin-1 -2, -6, and -8, and tumor necrosis
      factor in patients with colorectal cancer correlated with tumor stages and
      survival. METHODOLOGY: Serum concentrations of individual cytokines in 164
      colorectal cancer patients were determined before operation by enzyme-linked
      immunosorbent assay. The clinical significance of each serum cytokine was
      evaluated in relation to tumor progression and survival. RESULTS: Levels of
      interleukin-6 and interleukin-8 were significantly higher in patients than in
      controls. The serum concentrations of interleukin-2 and interleukin-6 were
      correlated with Dukes' stages. Only the levels of interleukin-6 were found to be
      associated with patient survival by univariate analysis. However, multivariate
      analysis did not identify interleukin-6 level as an independent factor of
      prognosis. CONCLUSIONS: Elevation of serum cytokines, such as interleukin-6, may
      be related to the development and progression of colorectal cancer. Interleukin-6
      level is associated with the clinical outcome, but is not an effective prognostic
      predictor.

PMID- 14696432
TI  - Chemopreventive effect of a probiotic preparation on the development of
      preneoplastic and neoplastic colonic lesions: an experimental study.
AB  - BACKGROUND/AIMS: A number of studies have suggested a key role played by certain
      resident gut bacteria in the development of large bowel cancer. The aim of the
      present study was to test the effect of a novel symbiotic preparation, which has
      been recently shown to beneficially modify gut ecosystem and systemic immunity,
      on either preneoplastic and neoplastic changes in a colon carcinogenesis model.
      METHODOLOGY: Sprague-Dawley rats were fed a standard diet for 1 week and then
      were randomly assigned to three groups. The control diet was given to groups A
      and B, whereas in group C, the same diet plus 2 mL of a probiotic mixture was
      given throughout the experiment. Thirty rats (groups B, C) each received a weekly
      subcutaneous injection of azoxymethane at a dose of 15 mg/kg of body weight for
      10 weeks. Group A served as a control group and received a subcutaneous injection
      of saline for 10 weeks. Forty-five rats were sacrificed at 3-week observation and
      60 rats at 20-week observation for assessing metaphase index together with
      aberrant crypt foci and intestinal immune system markers from one hand and tumor
      occurrence from the other, respectively. RESULTS: Group A showed a significantly
      increased metaphase index either in aberrant crypt foci or in "normal appearing"
      crypts when compared to group A (p < 0.01). Group B rats caused a significant
      decrease at both sites (p < 0.05). The numbers of lymphocytes derived from the
      mesenteric lymph nodes in group B rats were significantly decreased (p < 0.01) as
      compared to either control and to group C. The percentage of CD8 lymphocytes in
      group C was significantly higher than that in group B. Group C showed a
      significantly reduced ratio of aberrant crypt foci/colon and of aberrant crypt
      per colon and per each single focus (p < 0.05). A total of 18 (90%) group B and
      10 (50%) group C rats had colon tumors, this difference was significant. The mean
      number of colon tumors per rat was 2.2 and 1.0 in group B and C, respectively.
      CONCLUSIONS: Effective probiotics treatment, through mechanisms still to be fully
      elucidated (decreased fecal pH, specific reduction of carcinogenetic bacterial
      enzymes, modulation of gut-associated and systemic immune system etc.) has the
      potential to exert significant antimutagenic properties against colon cancer.

PMID- 14696433
TI  - Repetitive chemoembolization with melphalan plus intra-arterial immuno
      chemotherapy within 5-fluorouracil and granulocyte-macrophage colony-stimulating
      factor (GM-CSF) as effective first- and second-line treatment of disseminated
      colorectal liver metastases.
AB  - BACKGROUND/AIMS: In order to improve local and systemic efficacy of
      chemotherapeutic interventions we have used a combination of high concentrated
      plus low continuous regional chemotherapy modulated by GM-CSF cytokine in the
      treatment of inoperable colorectal liver metastases. METHODOLOGY: Sixty-six
      patients with disseminated inoperable colorectal liver metastases received
      continuous intra-arterial chemotherapy with 5-FU plus GM-CSF short time
      application plus chemoembolization Melphalan via an angiographically positioned
      hepatic artery catheter. The regimen consisted of the following steps: On day 1 +
      2 1400 mg/m2 5-FU administered intra-arterially in a continuous circadian mode,
      60 mg/m2 Rescuvolin given i.v. as a 2-hour infusion, 80 micrograms/m2 GM-CSF
      given i.a. as a 1-hour infusion, day 3 chemoembolization with 25 mg/m2 Melphalan
      plus Lipiodol and Gelfoam. RESULTS: 66 patients (38 male/28 female) with a median
      age of 60.4 years and a median Karnofsky index of 87.3 were treated with 299
      cycles of immunochemoembolization. Fifty-four percent of these patients had
      received prior systemic chemotherapy. Side effects were manifested in all
      patients, mainly upper abdominal pain lasting one to four days and grade 1 or 2
      vomiting. Systemic side effects were mild and transient with a very low rate of
      leukopenia. Using World Health Organization response criteria, the following
      responses could be demonstrated CR 1.0%, PR 42.4%, MR 24.2%, SD 18.2%, NR 12.1%.
      Time to progression was 8 months. Median survival has not been reached after an
      observation time of 28 months. Two-year survival was 66%. There was no
      statistically significant difference between chemonaive patients and patients
      pretreated by any kind of systemic therapy. CONCLUSIONS: Repetitive high
      concentrated regional chemotherapy by use of chemoembolization combined with
      continuous administered 5-FU and supplemented with GM-CSF is an effective tool in
      the therapy of disseminated colorectal liver metastases as front line as well as
      a second-line treatment.

PMID- 14696434
TI  - Prognostic value of DNA ploidy patterns of colorectal adenocarcinoma.
AB  - BACKGROUND/AIMS: The significance of prognostic value of DNA ploidy patterns of
      colorectal cancer has not yet been fully understood. The present study was
      designed to determine the prognostic value of DNA ploidy patterns for colorectal
      adenocarcinomas after resection. METHODOLOGY: We have prospectively collected
      tumor specimens from 420 patients with colorectal cancer since 1996. The DNA
      ploidy patterns were determined with the use of DNA flow cytometry. The
      correlation of DNA ploidy pattern and various characteristics of tumors and the
      prognostic significance of DNA ploidy patterns were evaluated by univariate as
      well as Cox's proportional hazard model. The disease-free survival curves were
      calculated with Kaplan-Meier's analysis, and the survival difference was
      determined by log-rank test. RESULTS: DNA ploidy patterns were diploid in 115
      (27.4%) and aneuploid in 305 patients (72.6%). The pattern of DNA ploidy did not
      correlate with age, gender, location, differentiation, and stage of the tumors.
      In 146 patients who were followed up for at least 2 years, the disease-free
      survival curves were similar between the diploid and aneuploid group.
      Multivariate analysis disclosed that tumor staging was associated with the
      survival of patients but the DNA ploidy pattern had no prognostic significance.
      CONCLUSIONS: The DNA ploidy pattern was not a significant prognostic factor in
      short-term follow-up.

PMID- 14696435
TI  - A late complication of pelvic radiotherapy: leiomyosarcoma of the rectum. Report
      of a case and review of the literature.
AB  - Leiomyosarcoma of the rectum is an uncommon malignancy; it accounts for less than
      0.1% of all malignancies of the colon and rectum and only one case has been
      reported long-term following pelvic radiotherapy. We report a second case of
      leiomyosarcoma of the rectum after radiotherapy in an elderly women who received
      external radiation therapy eighteen years before, for endometrial carcinoma. We
      confirm that leiomyosarcoma may be a late uncommon effect of pelvic irradiation
      and suggest that close and long-term surveillance of irradiated patients is
      highly recommended.

PMID- 14696436
TI  - Radiofrequency ablation in the treatment of pelvic recurrence of rectal cancer.
AB  - The aim was to assess the response to the treatment using thermal radiofrequency
      ablation in patients with pelvic recurrent rectal cancer. The location of the
      lesions as well as the placement of the percutaneous probe were guided by
      computed tomography. All ablations were performed with a RITA Medical Systems
      Starburst XL (nine-array, 5-cm) thermal ablation catheter and the Model 1500
      generator (RITA Medical Systems, Inc.). The radiofrequency ablation treatment was
      performed in two patients with pelvic recurrent rectal cancer with poor response
      to chemoradiotherapy with no indication of new surgical treatment and suffering
      strong pain in the sacrum area. The serum carcinoembryonic antigen had a sharp
      reduction in a sixty-day period. The post-procedure tomography analysis showed
      the center of the tumor with necrosis and a ring of edema around it. Both
      patients had no complaints about the procedure, and they needed to take mild
      analgesics only on the first day right after the procedure for pain. In the
      follow-up one patient developed an abscess and needed to be readmitted but
      without recurrent pelvic pain. An effective response was shown by tumor necrosis
      and total relief of pain of the sacrum area.

PMID- 14696437
TI  - Endoscopic management of upper gastrointestinal bleeding from a duodenal
      diverticulum.
AB  - Hemorrhage from duodenal diverticulum is a rare cause of upper gastrointestinal
      hemorrhage. The side-viewing endoscope was used for almost all cases of diagnosis
      and endoscopic hemostasis. However, a forward-viewing endoscope is used in
      emergent endoscopic study for upper gastrointestinal hemorrhage. We report a case
      in which the endoscopic hemostasis of bleeding duodenal diverticulum was
      performed during emergent forward-viewing endoscopic study.

PMID- 14696438
TI  - Nutritional assessment in patients with squamous cell carcinoma of the esophagus.
AB  - BACKGROUND/AIMS: Protein-calorie malnutrition that occurs in patients with
      squamous cell carcinoma of the esophagus presents defined implications in
      surgical results. The present study aims to establish a nutritional score for
      malnutrition to measure the prevalence of protein-calorie malnutrition and to
      determine parameters with higher discriminatory power for protein-calorie
      malnutrition diagnosis. METHODOLOGY: Forty-five (45) patients with squamous cell
      carcinoma of the esophagus (cases) and 90 surgical patients (controls) were
      analyzed using twelve parameters: percentage of body weight loss, triceps and
      subscapular skin fold, mid arm circumference and arm muscle circumference, serum
      total proteins, albumin, transferin, pre-albumin, hematocrit, total lymphocyte
      count and late hypersensitivity skin tests. Prognostic Nutritional Index was
      calculated for all patients. RESULTS: There was a statistically significant
      difference between the two groups (p < 0.05) regarding all evaluated parameters
      except late hypersensitivity skin tests. Patients were classified as malnourished
      when presented with six or more altered parameters. Through the proposed score,
      the prevalence of protein-calorie malnutrition was defined in cases (57.8%) and
      in controls (7.8%) groups with statistic significant difference (p = 0.001).
      CONCLUSIONS: The proposed score allowed the diagnosis of malnourished patients,
      defined the malnutrition prevalence in both groups and established parameters
      with a greater discriminatory power for the protein-calorie malnutrition
      diagnosis.

PMID- 14696439
TI  - Outcome of patients with cancer of the esophagogastric junction in relation to
      histology and surgical strategy.
AB  - BACKGROUND/AIMS: The impact of histologic type and surgical strategy on survival
      of patients with cancer of the esophagogastric junction is debated. Thus, we
      evaluated the relationship between cancer histologic type (adenocarcinoma vs.
      squamous cell carcinoma) on long-term survival and the results of two different
      surgical techniques on outcome. METHODOLOGY: Two hundred and one patients with
      neoplasm of the esophagogastric junction were prospectively observed, and 133
      patients (66%) underwent operation with curative intent. The results of two
      resective techniques, total gastrectomy with a thoraco-abdominal approach and
      total gastrectomy with a trans-hiatal approach were also compared in a subgroup
      with Siewert's type II and III cancer. RESULTS: Seventy-seven patients had an
      adenocarcinoma and 56 a squamous cell carcinoma. The 5-year proportion of
      survival was 35% in the adenocarcinoma group versus 40% in the squamous group
      (log-rank = 0.92), and the mean length of survival was 35 +/- 3 months and 34 +/-
      5 months, respectively. The overall incidence of postoperative morbidity and the
      length of hospital stay were both significantly lower in the trans-hiatal group
      than in the thoraco-abdominal group (31% vs. 51%; p = 0.04; and 15.6 days vs.
      23.2 days; p = 0.02 respectively), while the 5-year patient survival was 37%
      thoraco-abdominal approach and 42% in the trans-hiatal approach (log-rank =
      0.62). CONCLUSIONS: In the present population, histologic type of the
      esophagogastric cancer was not a determinant factor for long-term survival. The
      transhiatal approach resulted in a better postoperative outcome without
      compromising surgical radicality and patient survival.

PMID- 14696440
TI  - Alcohol and esophageal cancer, is there an exaggerated accusation?
AB  - Difficulty in its early diagnosis, fast progression and high mortality makes
      esophageal carcinoma one of the most important fatal diseases in the world. Its
      unequal geographic distribution gives a hint to clinicians and epidemiologists an
      impression that this disease is definitely related to environmental factors.
      Deficiencies in essential vitamins and other substances in diet have been blamed
      for many years. Tobacco and alcohol were also found guilty for a long time. But a
      great majority of people in high-risk areas are Moslem and teetotalers. Therefore
      some other factors as nitrosamines, which were found to enhance the risk of
      esophageal carcinoma, should be also emphasized in the etiology of the disease.
      Nitrosamines are most likely acting as the promoters in the carcinogenesis of
      esophagus. It is difficult to explain the importance of alcohol in high-risk
      areas where most of the people are teetotalers.

PMID- 14696441
TI  - Surgery for perforated peptic ulcer in the elderly. Evaluation of factors
      influencing prognosis.
AB  - BACKGROUND/AIMS: The frequency of perforated peptic ulcer is decreasing among the
      overall population but it is becoming more frequent among old people. The higher
      mortality rate in the old population, justifies the search of prognostic factors
      specific for the elderly. Aim of this study is to analyze and define factors
      influencing surgical prognosis in patients older than 70 years who were operated
      for perforated peptic ulcer. METHODOLOGY: A retrospective analysis of 37 patients
      was performed: age, sex, ASA status, site of perforation, diameter of
      perforation, duration of symptoms, MPI score, surgical treatment (suture vs.
      resection) were studied. All patients were grouped as deceased and not deceased
      after surgery: a statistical univariate analysis was performed regarding the
      whole series and regarding the patients 70 years and older. RESULTS:
      Postoperative mortality rate was 18.92% in the whole series but 41.8% among the
      elderly. In the whole series age, ASA status, diameter of perforation, duration
      of symptoms, and MPI score were significantly related to postoperative death. In
      the patients 70 years and older the duration of symptoms, the size of perforation
      and the MPI score were significantly related to postoperative death. CONCLUSIONS:
      The duration of symptoms is a known factor that influences the prognosis after
      surgery for perforated peptic ulcer. This factor is still the most important in
      the elderly being responsible of the high mortality rate. The delay in treatment
      is due to a delayed hospitalization of old patients, who show a low reactivity to
      the disease.

PMID- 14696442
TI  - Upper gut motility of Hirschsprung's disease and its allied disorders in adults.
AB  - BACKGROUND/AIMS: To clarify the significance of upper gut motility for
      Hirschsprung's disease and its allied disorders in adults, we studied the upper
      esophagogastroduodenal motility of adult patients with Hirschsprung's disease and
      its allied disorders such as hypoganglionosis and intestinal neuronal dysplasia.
      METHODOLOGY: Twelve patients (7 men and 5 women, aged between 20 and 55 years
      with a mean age of 39.6 years) with Hirschsprung's disease (2 cases) or its
      allied disorders (8 cases of hypoganglionosis and 2 cases of intestinal neuronal
      dysplasia) were studied. As a control, 15 healthy volunteers (8 men and 7 women
      aged between 27 and 69 years with a mean age of 49.0 years) were also examined.
      To obtain the upper gut motility in Hirschsprung's disease, hypoganglionosis, and
      intestinal neuronal dysplasia, we performed gastrointestinal transit time study,
      esophageal manometry, and gastroduodenal manometry. RESULTS: On gastrointestinal
      transit time, barium stagnated in the upper jejunum in 2 cases of
      hypoganglionosis, in the terminal ileum in one case of hypoganglionosis and
      intestinal neuronal dysplasia, and in the colon in the remaining patients. In two
      of the 12 cases of Hirschsprung's disease and its allied disorders such as
      hypoganglionosis and intestinal neuronal dysplasia, abnormal esophageal
      motilities, and absence of interdigestive migrating motor complex, phase III from
      the stomach were observed. These findings suggested that the entire digestive
      tract might have been affected in these two cases, i.e., these 2 patients had
      total gut involvement type of hypoganglionosis. CONCLUSIONS: Gastrointestinal
      transit time and upper esophagogastroduodenal manometry should be performed
      because of the relatively frequent association of upper gut dysmotilities with
      these disorders.

PMID- 14696443
TI  - Significance of rapid turnover proteins in protein-losing gastroenteropathy.
AB  - BACKGROUND/AIMS: We investigated the significance of rapid turnover proteins
      (retinal-binding protein, pre-albumin and transferrin) in protein-losing
      gastroenteropathy. METHODOLOGY: We evaluated the levels of these proteins in 12
      patients with protein-losing gastroenteropathy. RESULTS: The protein-losing
      gastroenteropathy patients showed very low level of total serum protein of 4.3 +/
      0.7 g/dL, albumin 2.1 +/- 0.4 g/dL, and IgG 682 +/- 232 mg/dL. However, retinal
      binding protein was 4.4 +/- 1.9 mg/dL (normal range; 2.5-8.0 mg/dL), pre-albumin
      29.3 +/- 7.9 mg/dL (21-43 mg/dL) and transferrin 226 +/- 62 mg/dL (205-370
      mg/dL). The levels of rapid turnover proteins, particularly retinal-binding
      protein and pre-albumin were almost preserved within the normal range, despite
      hypoproteinemia. CONCLUSIONS: If there is a patient with severe hypoproteinemia
      and preserved levels of rapid turnover proteins, protein-losing gastroenteropathy
      should be suspected and we get a strong proof to do the following examinations
      such as a fecal clearance of alpha-1 antitrypsin.

PMID- 14696444
TI  - Study of the effect of jejuno-ileal distension on the motor activity of the
      stomach with evidence of "entero-gastric inhibitory reflex".
AB  - BACKGROUND/AIMS: In chronic constipation due to delayed colonic transit, stasis
      of the ileal contents with resulting ileal distension may occur. The current
      study investigated the effect of ileal and jejunal distension on the gastric
      motility, aiming at elucidating the possible existence of a relationship and its
      role in the flow through the gut. METHODOLOGY: The response of the gastric
      pressure to ileal and jejunal balloon distension in increments of 2 mL of saline
      was recorded in 12 mongrel dogs. The test was repeated after separate local
      anesthetization of the ileum, jejunum and stomach. RESULTS: 2- and 4-mL ileal
      balloon distension produced no significant gastric pressure response, while 6-
      and up to 10-mL distension effected decrease of the antral and corporeal
      pressures (p < 0.05, p < 0.05, respectively). Jejunal distension produced a
      gastric pressure decline (p < 0.05) with 4 and up to 10 mL of saline. The gastric
      pressure decrease did not show significant changes with the various distending
      volumes. It was maintained as long as ileal or jejunal distension was continued.
      Distension of the anesthetized ileum or jejunum caused no gastric pressure
      changes, nor did ileal or jejunal distension produce pressure changes in the
      anesthetized stomach. CONCLUSIONS: The gastric pressure decline and presumably
      hypotonia upon ileal or jejunal distension with big volumes postulate a reflex
      relationship which we call "entero-gastric inhibitory reflex". The small
      intestine is suggested to slow down gastric emptying through this reflex. A
      balance is thus created between chyme delivery from the stomach and chyme
      processing by the small intestine. Reflex derangement in neurogenic and myogenic
      diseases may result in gastrointestinal disorders, a point that needs to be
      investigated.

PMID- 14696445
TI  - The effects of a selective cyclooxygenase-2 inhibitor on small bowel ischemia
      reperfusion injury.
AB  - BACKGROUND/AIMS: The purpose of this study was to investigate the effects of a
      selective COX-2 inhibitor, FK3311, on warm ischemia-reperfusion injury of the
      canine small intestine. METHODOLOGY: Ten adult mongrel dogs were used. FK (1
      mg/kg) was administered intravenously 15 minutes prior to ischemia and 15 minutes
      prior to reperfusion in the FK group (n = 5), and only an inert vehicle was
      injected in the control group (n = 5). The superior mesenteric artery and vein
      were clamped closed for 2 hours and then unclamped for 12 hours of reperfusion.
      Arterial and intramucosal pH were measured, and samples were taken for
      histological examination at 1, 3, 6, and 12 hours after the start of reperfusion.
      Serum thromboxane B2 and 6-keto-prostaglandin F1 alpha (stable metabolites of
      TxA2 and PGI2) were measured 30 minutes after reperfusion began. RESULTS:
      Arterial and intramucosal pH changes were significantly (p < 0.05) smaller in the
      FK group than in the control group. Histological ischemia-reperfusion injury was
      significantly (p < 0.05) more severe in the control group than in the FK group.
      Serum thromboxane B2 and 6-keto-prostaglandin F1 alpha levels were significantly
      (p < 0.05) lower in the FK group compared to the control group. CONCLUSIONS: FK
      protects the small bowel from ischemia-reperfusion injury by suppression of
      prostanoid production.

PMID- 14696447
TI  - Effects of parasympathetic blockade on hepatic and portal venous flow.
AB  - BACKGROUND/AIMS: To investigate the effect of parasympathetic blockade on the
      hepatic circulation, a study was performed in healthy men because the precise
      knowledge of factors to affect the hepatic circulation is required for the
      evaluation of liver diseases. METHODOLOGY: Doppler measurements of the hepatic
      venous and portal venous flow were obtained with measurements of cardiac function
      before and after the administration of atropine sulfate, 0.02 mg/kg. RESULTS:
      Parasympathetic blockade increased heart rate and cardiac output and changed
      diastolic right ventricular filling pattern. However, portal venous flow remained
      unchanged. Hepatic venous flow was triphasic at rest in 15 of the 20 subjects
      (75%). The amplitude of the oscillation of hepatic venous flow velocity was
      significantly reduced in association with an increase in heart rate and the
      hepatic venous flow pattern was significantly influenced by parasympathetic
      blockade in accordance with a change in right ventricular filling pattern.
      CONCLUSIONS: The autoregulation of portal venous flow was suggested to exist and
      that the influences of parasympathetic activity and/or heart rate affected
      hepatic venous flow pattern.

PMID- 14696446
TI  - Multiple giant duodenal gallstones causing gastric outlet obstruction: Bouveret's
      minefield revisited.
AB  - Gastric outlet obstruction caused by a gallstone impacted in the duodenum is a
      rare entity known as Bouveret's syndrome. We report the unusual case of multiple
      large gallstones impacted in the duodenum from a cholecystoduodenal fistula in an
      83-year-old lady. A high index of suspicion allowed for prompt diagnosis. Early
      surgical intervention was instituted because if the size and number of gallstones
      with an excellent outcome. The surgical strategies and underlying pitfalls
      underlying the management of this syndrome are critically reviewed and discussed.

PMID- 14696448
TI  - Bone scintigraphy of skeletal metastasis in hepatoma patients treated by TAE.
AB  - BACKGROUND/AIMS: Skeletal metastasis in hepatocellular carcinoma patients has
      become clinically important as a result of advances in treatment modalities.
      However, the diagnostic accuracy of bone scintigraphy in hepatocellular carcinoma
      has been questioned. METHODOLOGY: 99mTc-MDP bone scintigraphy was performed in 63
      unresectable hepatocellular carcinoma patients treated by transcatheter arterial
      embolization who either developed musculoskeletal pain (n = 43) or elevated serum
      alpha-fetoprotein levels (n = 20) during follow-up. Results were categorized as
      positive or negative for metastases, and their accuracy was evaluated by
      radiological studies, biopsy, and clinical follow-up. RESULTS: Bone scintigraphy
      was positive in 22/43 (51.2%) subjects with pain and 2/20 with alpha-feto-protein
      elevation. Among 24 bone scintigraphy(+) patients, metastasis was confirmed in 17
      and excluded in 6. Frequent sites for metastatic bone scintigraphy lesions were
      the spine, pelvic bone and ribs. Although 8 metastatic lesions had low or mixed
      uptake, most had increased uptake on bone scintigraphy. Among 39 bone
      scintigraphy(-) patients, metastasis was excluded in 32 and confirmed in 1. The
      sensitivity and specificity of bone scintigraphy in this subset of patients was
      94.4% and 84.2%, respectively. CONCLUSIONS: Transcatheter arterial embolization
      treated hepatocellular carcinoma patients with musculoskeletal pain have a high
      likelihood of bone metastasis, and bone scintigraphy is a highly reliable method
      for its detection.

PMID- 14696449
TI  - Profile of hepatocyte growth factor in patients with obstructive jaundice.
AB  - BACKGROUND/AIMS: Hepatocyte growth factor is a potent growth-stimulating factor
      of many kinds of tissue. Hepatocyte growth factor was demonstrated in the blood
      of various liver diseases, and its concentration was reported to correlate with
      liver function after partial hepatectomy. In this study, we monitor the dynamics
      of bile hepatocyte growth factor in patients with obstructive jaundice.
      METHODOLOGY: In a university hospital, 68 paired blood and bile samples from 42
      patients with hyperbilirubinemia were determined with ELISA. The hepatocyte
      growth factor bile/blood ratio and both daily hepatocyte growth factor clearance
      and output were calculated for each pair. The correlations between these values
      with other biochemical parameters were then determined. RESULTS: The blood
      hepatocyte growth factor concentration correlated positively with serum bilirubin
      (r = 0.556, p < 0.001) level, whereas bile hepatocyte growth factor
      concentration, hepatocyte growth factor bile/blood ratio, hepatocyte growth
      factor clearance and daily hepatocyte growth factor output correlated negatively
      with serum bilirubin level (p = 0.006, < 0.001, < 0.001 and 0.002, respectively).
      Similar strong positive correlations also were found to exist between these
      hepatocyte growth factor measurements and other liver function parameters.
      CONCLUSIONS: In this study we demonstrated that the hepatocyte growth factor was
      significantly higher in bile than in blood and that the excretion of hepatocyte
      growth factor in the bile was decreased in patients with obstructive jaundice.
      The higher blood hepatocyte growth factor level in patients with obstructive
      jaundice might be due to decreased hepatocyte growth factor excretion. The higher
      hepatocyte growth factor level in bile also might explain why liver cirrhosis
      occurs after prolonged jaundice.

PMID- 14696450
TI  - Accompanying liver cirrhosis as a risk factor for recurrence after resection of
      solitary hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: A high recurrence rate after hepatic resection adversely
      influences the postoperative prognosis of patients with hepatocellular carcinoma.
      In the present study, long-term results and prognostic factors were evaluated in
      patients who underwent hepatic resection for solitary hepatocellular carcinoma.
      METHODOLOGY: The records of 105 patients who underwent hepatic resection for
      hepatocellular carcinoma between June 1978 and April 2000 were retrospectively
      reviewed. In 61 patients with solitary hepatocellular carcinoma who survived the
      curative operation, the prognostic significance of 11 clinicopathological
      parameters was investigated by univariate and multivariate analyses. RESULTS:
      After curative resection, the cumulative survival rate at 5 years in these 61
      patients with solitary hepatocellular carcinoma was significantly better than in
      25 patients with multiple hepatocellular carcinomas (44% vs. 25%, p = 0.01).
      However, even in the solitary group, the cumulative recurrence-free survival rate
      at 5 years was only 32%; and in 27 (75%) of 36 patients, in whom recurrence was
      confirmed within 5 years, hepatocellular carcinoma recurred within 2 years.
      Multivariate analysis disclosed that only accompanying liver cirrhosis was a
      variable having prognostic significance for overall and recurrence-free survival.
      A study of other clinicopathological factors, including tumor size, failed to
      demonstrate any prognostic value. CONCLUSIONS: The present result suggests that
      hepatic resection can be indicated in patients with solitary hepatocellular
      carcinoma, irrespective of its size. Though the postoperative recurrence
      associated with the underlying cirrhosis is still frequent, long-term survival
      can be expected if the recurrent tumors are successfully treated by a strategy
      using multiple modalities.

PMID- 14696451
TI  - Intraabdominal arterio-venous fistulae and their relation to portal hypertension.
AB  - BACKGROUND/AIMS: The aim of the study was to present, on the base of own
      experience, clinical importance of arterio-venous fistulae involving the vascular
      system of the abdomen. METHODOLOGY: Clinical material consists of 18 patients in
      whom abnormal arterio-venous leakage in the abdomen was disclosed by means of
      imaging diagnostic techniques and Doppler sonographic hemodynamic investigations.
      Three groups of patients were determined: 1. Patients in whom arterio-venous
      fistula was a primary cause of portal hypertension (N = 6), 2. Patients in whom
      the presence of arterio-venous fistulae aggravated portal hypertension due to
      other pathology (N = 7). 3. Patients in whom the arterio-venous fistulae did not
      directly affect portal flow (N = 5). As each case presented a different clinical
      problem, the therapeutic approach had to be individualized. In 12 patients
      perarterial embolization was performed, 13 patients were operated on, one patient
      was listed for liver transplantation. RESULTS: Perarterial embolization was fully
      effective only in 4 cases. In the remaining 8 cases its effect was transient, but
      in 4 cases of liver tumors it allowed us to proceed with chemoembolization and
      the others were subsequently treated surgically. In 12 surgically treated
      patients the operation proved to be curative. In 1 case of multiple arterio
      venous fistulae related to diffuse angiomatosis, surgical procedure was
      unfeasible. One patient, awaiting liver transplantation, died of liver failure.
      CONCLUSIONS: 1. Arterio-venous fistulae (of various etiology) are rarely found in
      the abdominal cavity, but their presence means usually serious consequences
      depending on their morphology and localization. 2. Arterio-venous fistulae
      involving the portal system may result in severe portal hypertension. 3.
      Individually chosen method of treatment, aimed at the occlusion of arterio-venous
      fistula often proves to be curative. 4. Overlooking or ignoring the presence of
      intraabdominal arterio-venous fistulae leads to unsuccessful, if not harmful
      treatment.

PMID- 14696452
TI  - Calibrated portacaval H-graft shunt in variceal hemorrhage. Long-term results.
AB  - BACKGROUND/AIMS: To analyze the long-term outcome of the calibrated portacaval
      shunt in the treatment of portal hypertension. METHODOLOGY: Between 1991 and 1996
      we undertook a prospective non-randomized study, including 37 cirrhotic patients
      who underwent small diameter portacaval shunt with polytetrafluoroethylene H
      graft, 24 cases with 8 mm and 13 cases with 10 mm. Early and late complications,
      and survival were analyzed. RESULTS: Overall, 28 corresponded to Child-Pugh class
      A, 5 to class B and 4 to class C. The cause of cirrhosis was alcoholic in 16
      cases, postnecrotic in 12, mixed in 5, primary biliary cirrhosis in 2 and unknown
      in 1. Postoperative mortality was 10%. Long-term results, after a follow-up of 3
      8 years, have shown a rebleeding rate of 12%, mainly after the third
      postoperative year. Some degree of encephalopathy occurred in 23% of the
      patients, but in no case was this chronic or incapacitating. The rate of early
      thrombosis was 5%, but in all cases it was repermeabilized with local
      thrombolysis. The late thrombosis rate was 6%. The 3-, 5- and 7-year survival
      rates were 79%, 57%, and 36%, respectively. These rates were not statistically
      related with the shunt diameter or the etiology of the cirrhosis. CONCLUSIONS:
      Partial portacaval shunt is a safe option for the treatment of variceal bleeding
      due to portal hypertension. We consider it to be the treatment of choice in a
      selected group of cirrhotic patients with well-preserved liver function, after
      previous failure of medical therapy. Furthermore, it can also be used as a bridge
      until liver transplantation.

PMID- 14696453
TI  - Clinical characteristics of patients with cryptogenic liver cirrhosis in Okinawa,
      Japan.
AB  - BACKGROUND/AIMS: The aims of the present study were to determine the prevalence
      of patients with cryptogenic liver cirrhosis, and to clarify the clinical
      characteristics of these patients, with special focus on obesity and type 2
      diabetes mellitus. METHODOLOGY: For the case-control study, we selected age- and
      sex-matched control patients with cirrhosis of known etiology. RESULTS: Of 404
      patients with liver cirrhosis, 40 (9.9%) were diagnosed as having cryptogenic
      cirrhosis. Of these 40 patients, 29 (73%) were female. The mean age was 66.1 +/-
      8.9 (range 40-87 years old), and was significantly higher than that of either
      virus, or alcohol-related liver cirrhosis patients. Both obesity and type 2
      diabetes mellitus were more common in patients with cryptogenic cirrhosis (53%
      and 40%, respectively) compared with the case-controls (20%, 18%, respectively).
      CONCLUSIONS: Cryptogenic liver cirrhosis accounted for approximately 10% of liver
      cirrhosis, and was associated with both obesity and type 2 diabetes mellitus.
      Nonalcoholic steatohepatitis sequelae may be the most important etiological
      factor in patients with cryptogenic liver cirrhosis in Okinawa, Japan, where
      virus-etiology is more predominant in liver cirrhosis compared with Western
      countries.

PMID- 14696454
TI  - Disease and treatment outcome in chronic active hepatitis C with occult HBV
      infection.
AB  - BACKGROUND/AIMS: To evaluate the clinical course and effect of antiviral
      treatment in chronic active hepatitis C with coexisting occult hepatitis B
      infection. METHODOLOGY: Basic liver enzymes, histological activity of hepatitis
      (Ishak score), biochemical and virological response rate at the end of treatment
      and 6 months later of 30 patients (15 of them positive for hepatitis B core
      antibody in serum) with chronic active hepatitis C are compared. All patients
      were treated with Interferon alpha-2b 3ME three times weekly and oral Ribavirin
      1000/1200 mg daily for six months. RESULTS: The pure hepatitis C group
      demonstrates markedly higher biochemical and histological (necroinflammatory)
      activity. After treatment the pure hepatitis C group shows normalization of serum
      ALT in 73% (vs. 66% in hepatitis B core antibody-positive patients); loss of
      detectable HCV-RNA in serum in 47% (vs. 35%) and sustained biochemical response 6
      months later in 28% vs. 40% respectively. CONCLUSIONS: Patients with circulating
      hepatitis B core antibodies might develop some degree of immune tolerance against
      hepatitis C virus, with less advanced hepatolysis and necroinflammation even in
      the presence of HCV viremia and worse virological therapeutic response,
      associated with frequent sustained ALT normalization.

PMID- 14696455
TI  - Long-term follow-up of patients with liver cirrhosis after endoscopic esophageal
      varices ligation therapy: comparison with ethanol injection therapy.
AB  - BACKGROUND/AIMS: Esophageal variceal hemorrhage is the most dreaded complication
      of liver disease. Prevention or emergency therapy of bleeding is important.
      METHODOLOGY: A group of 217 patients underwent endoscopic esophageal variceal
      therapy including endoscopic ethanol injection, endoscopic esophageal variceal
      ligation, or a combination of the two. RESULTS: Esophageal varices were
      eradicated by endoscopic esophageal variceal ligation with the least sessions
      required, and associated complications with endoscopic esophageal variceal
      ligation therapy were lower than with the other two approaches. However, the
      cumulative recurrence-free period of esophageal varices was significantly higher
      after endoscopic ethanol injection than after endoscopic esophageal variceal
      ligation and in some cases F3 varices were observed post-endoscopic esophageal
      variceal ligation hemorrhage. A combined endoscopic esophageal variceal ligation
      and endoscopic ethanol injection therapy had no advantage with respect to
      cumulative recurrence-free rate, session number, or complication frequency,
      relative to either therapy alone. CONCLUSIONS: While the combined observations
      indicate that endoscopic esophageal variceal ligation is safe and simple, we
      should consider additional therapy to achieve complete mucosal fibrosis of the
      esophagus after endoscopic esophageal variceal ligation.

PMID- 14696456
TI  - Liver stellate cells and aminoterminal peptide of type III procollagen in chronic
      hepatitis C treated with interferon.
AB  - BACKGROUND/AIMS: Fibrogenesis plays a crucial role in development of cirrhosis,
      and liver stellate cells, activated to myofibroblasts expressing alpha-smooth
      muscle actin, are responsible for deposition of fibrous matrix; aminoterminal
      peptide of type III procollagen is a serum marker of active fibrogenesis.
      Interferon can slow ongoing fibrogenesis in chronic viral hepatitis, but it
      remains unclear whether the drug acts by a direct effect on stellate cells or by
      inhibiting the necro-inflammatory process. The aim of this study was to evaluate,
      in selected cases of chronic hepatitis C, whether changes in stellate cell
      expression induced by interferon correlated with changes in serum levels of
      procollagen or with clinical response to the therapy, in order to further
      investigate the mechanism of interferon's effect on fibrogenesis. METHODOLOGY: We
      studied 30 patients with chronic hepatitis C, treated with interferon and
      followed for more than 6 months. Before and after-treatment evaluation included
      histological scores for portal activity, lobular activity and fibrosis;
      immunohistochemical scores for alpha-actin expression by activated stellate cells
      in liver biopsy; and radioimmunoassay for procollagen in serum. According to the
      clinical response to interferon, the patients were subdivided into sustained
      responders, delayed relapsers, early relapsers and non-responders. RESULTS: We
      found that alpha-actin scores, portal and lobular activity scores and procollagen
      levels were all significantly lower after the treatment in responder patients,
      whereas in non-responders the after-interferon values were not different from the
      basal values. Moreover we found that the patients who were still clinical
      responders at the time of after-therapy evaluation, but relapsed subsequently
      (delayed relap-sers), still showed a pattern of "low fibrogenesis", like the
      sustained responders. On the contrary, the patients who had already relapsed at
      the time of after-interferon evaluation (early relapsers) showed a pattern of
      "high fibrogenesis", like the non-responders. CONCLUSIONS: Since all the patients
      had received a similar treatment for a similar period, our results suggest that
      fibrogenesis activity in a defined time is related to the clinical response
      present in that time, and is influenced by short-term variations in necro
      inflammatory activity induced by interferon, rather than by interferon itself.

PMID- 14696457
TI  - Comparison of the clinical characteristics among hepatocellular carcinoma of
      hepatitis B, hepatitis C and non-B non-C patients.
AB  - BACKGROUND/AIMS: The present study was undertaken to compare the clinical
      characteristics, availability of initial treatment options and prognostic
      features of patients with hepatocellular carcinoma in relation to hepatitis B or
      C viral infection. METHODOLOGY: Six hundred and ninety-two patients with
      hepatocellular carcinoma treated during the 12-year-period from Jan 1989 to Dec
      2000 were categorized into three groups as follows: 1) 59 were classified as the
      HBV group: positive for hepatitis B surface antigen (HBsAg) and negative for
      antibody to hepatitis C (HCVAb), 2) 594 were placed in the HCV group: negative
      for HBsAg and positive for HCVAb, and 3) 39 were put into the Non-B, Non-C (NBNC)
      group: negative for both HBsAg and HCVAb. The age distribution, gender ratio,
      serum alpha-fetoprotein level, the presence of underlying cirrhosis, tumor size,
      the number of hepatocellular carcinoma tumors at the initial detection, the types
      of follow-up until the initial detection of hepatocellular carcinoma, the initial
      treatments chosen, and the survival were analyzed and compared among the three
      groups. RESULTS: Regarding age, the HBV group showed a younger age (56.3 +/- 12.2
      years old) than the other two groups (the HCV group: 66.3 +/- 8.3, the NBNC
      group: 67.9 +/- 8.5 years old), however, no difference was observed in the male
      to-female ratio of the three groups. The serum alpha-fetoprotein level, the
      prevalence of hepatocellular carcinoma measuring more than 3 cm in diameter, non
      solitary hepatocellular carcinoma and portal thrombosis were strongly
      demonstrated at the initial detection in the HBV group, which was most likely due
      to the poor follow-up until detection. Consequently, the 1-, 3-, 5- and 7-year
      survivals of the patients in the HBV group were 40.4, 25.1, 18.8 and 5.2%, and
      were significantly shorter than both the HCV group which were 72.6, 44.9, 25.0
      and 10.0%, and the NBNC group which were 71.2, 41.4, 31.1 and 31.1%,
      respectively. As for the NBNC group, in spite of the lack of a careful follow-up
      a longer survival was observed probably because they had a better preserved liver
      condition. CONCLUSIONS: Regarding the hepatocellular carcinoma patients, those
      infected with HBV presented at the advanced stage due to the lack of a careful
      follow-up, thus resulting in a shorter survival. As a result, hepatocellular
      carcinoma patients infected with HBV need to be strictly followed up.

PMID- 14696458
TI  - Prevalence of pulmonary hypertension in patients with hepatosplenic Mansonic
      schistosomiasis--prospective study.
AB  - BACKGROUND/AIMS: Thirty-four patients with portal hypertension and previous
      history of esophageal varices hemorrhage due to hepatosplenic Mansonic
      schistosomiasis were prospectively studied. METHODOLOGY: All patients underwent
      invasive hemodynamic monitoring with introduction of a pulmonary artery catheter.
      Hemodynamic evaluation was characterized by an increased cardiac index (4.90 +/-
      1.27 L/min/m2) associated to a decrease in systemic vascular resistance index
      (1461 +/- 443.04 dynes.sec/cm5.m2). RESULTS: Mean pulmonary artery pressure
      (17.97 +/- 6.97 mmHg) and right atrial pressure (7.65 +/- 3.67 mmHg) were
      increased while pulmonary vascular resistance index was decreased (147.95 +/-
      126.21 dynes.sec/cm5.m2). Twenty-four patients (70.5%) presented pulmonary
      hypertension (mean pulmonary artery pressure > 15 mmHg); in fifteen (44.1%)
      pulmonary pressure was between 15 and 20 mmHg, in three between 20 and 25 mmHg
      and, in four patients, pulmonary pressure was higher than 25 mmHg. CONCLUSIONS:
      In conclusion, pulmonary hypertension is a frequent complication in patients with
      portal hypertension due to hepatosplenic Mansonic schistosomiasis and, in 20.6%
      of the cases, it can be considered as moderate or severe. Our results suggest
      that shunt surgeries, which can aggravate pulmonary hypertension, should be
      employed very cautiously in the treatment of schistosomal portal hypertension.

PMID- 14696459
TI  - The in vitro effect of interferon-alpha 2a on CD95 expression of T cells in
      hepatitis B.
AB  - BACKGROUND/AIMS: In chronic hepatitis B, apoptotic rate of peripheral cytotoxic T
      cells may be related with hepatocyte injury. We aimed to investigate Fas (CD95)
      expression of peripheral cytotoxic T cells and to show the in vitro effect of
      interferon-alpha 2a on Fas expression and apoptosis. METHODOLOGY: The study group
      consisted of 17 patients with chronic hepatitis B and control group consisted of
      10 healthy subjects. Apoptotic cells were identified by flow-cytometric assay
      using Annexin V and propidium iodide. We used monoclonal antibodies stained by
      direct immunofluorescent method to show surface molecules. CH-11 monoclonal
      antibodies were used as anti-Fas antibodies. RESULTS: Basal expressions of CD95
      and CD8+ CD95+ in the peripheral mononuclear cells were higher in chronic
      hepatitis B patients than controls. In vitro treatment with interferon-alpha 2a
      increased the percentage of CD8+ 95+ peripheral mononuclear blood cells in
      controls; this effect was less remarkable in patients with chronic B hepatitis,
      and the difference was not statistically significant. The number of apoptotic
      cytotoxic T cells also increased in 5 subjects of the study group and 3 subjects
      of controls; the percentage of CD95+ cells increased in 7 of 17 patients and 8 of
      10 controls. The percentage of CD8+ 95+ cells and the apoptotic rate of CD8+
      cells were not different between study group and controls after combined
      treatment with interferon-alpha 2a and monoclonal stimulating anti-Fas
      antibodies. CONCLUSIONS: We suggest that interferon-alpha 2a does not induce Fas
      dependent apoptosis in CD8+ peripheral T cells of the patients with chronic
      hepatitis B, and CD95 molecules on peripheral cytotoxic T cells might be
      defective.

PMID- 14696460
TI  - Factors affecting the prognosis of patients with hepatocellular carcinoma
      invading the portal vein--a retrospective analysis using 952 consecutive HCC
      patients.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma with portal venous invasion has a very
      poor prognosis. The aim of this study is to clarify the factors contributing to
      the survival of hepatocellular carcinoma patients with portal venous invasion.
      METHODOLOGY: Out of 952 patients with hepatocellular carcinoma admitted to Tokyo
      University hospital and its affiliated hospitals from 1987 to 1999, 53 patients
      developed portal venous invasion until December 2000. The main portal vein was
      invaded in 33 patients, and the first branch was invaded in the 20 patients. The
      factors contributing to the prognosis of hepatocellular carcinoma patients with
      portal venous invasion were determined by univariate and multivariate analyses
      using 19 clinicopathological parameters. RESULTS: Overall survival rates of the
      53 patients at 6 months, and 1 and 2 years were 40%, 18%, and 12%, respectively.
      Univariate analysis indicated that the serum albumin level, Child classification,
      number of tumor foci, portal venous invasion-targeted irradiation, and
      percutaneous tumor ablation of the parenchymal main tumor were significant.
      Multivariate analysis showed that percutaneous tumor ablation (P = 0.033; risk
      ratio = 0.28) was the most important factor contributing to a favorable prognosis
      followed by number of tumor foci (P = 0.048; risk ratio = 0.41). CONCLUSIONS:
      This study showed the significance of treatment for the parenchymal main tumor in
      addition to portal venous invasion in patients with hepatocellular carcinoma
      involving portal venous invasion. Therefore, the efficacy of combined therapy
      using portal venous invasion-targeted irradiation and percutaneous tumor ablation
      for the parenchymal main tumor on survival of hepatocellular carcinoma patients
      with portal venous invasion is suggested.

PMID- 14696461
TI  - Treatment of chronic hepatitis B with the sequential administration of interferon
      and lamivudine.
AB  - BACKGROUND/AIMS: Interferon monotherapy has been shown to induce a sustained
      viral response in 30-40% of patients with HbeAg-positive chronic hepatitis B
      infection. Similarly, lamivudine monotherapy causes HBeAg seroconversion in less
      than 20% of patients treated for one year. This study aims to assess the efficacy
      and safety of the sequential administration of interferon alfa-2a plus lamivudine
      to patients with chronic hepatitis B in comparison to lamivudine monotherapy.
      METHODOLOGY: Sixty-one patients with HbeAg-positive chronic hepatitis B infection
      and raised ALT were randomized to receive either interferon Alfa-2a, 4.5 million
      units daily for 16 weeks plus lamivudine 100 mg daily starting from week 5 and
      continuing for 48 weeks (Group A, n = 32) or lamivudine monotherapy for 48 weeks
      (Group B; n = 29). Patients were followed for 48 weeks after completion of
      therapy. RESULTS: HBeAg seroconversion to anti-HB +ve was observed in 2 (6.2%)
      patients in Group A. Both patients remained HBeAg negative and HBV-DNA negative
      throughout the follow-up phase. None of the group B patients seroconverted at the
      end of therapy or during follow-up (P = NS). All group A patients experienced at
      least one side effect and as a result, one dropped out. All group B patients
      completed the study without side effects. CONCLUSIONS: The sequential
      administration of interferon plus lamivudine was not superior to lamivudine
      monotherapy for the treatment of chronic hepatitis B and was associated with more
      side effects.

PMID- 14696462
TI  - Prognostic factors for hepatocellular carcinoma < or = 3 cm in diameter.
AB  - BACKGROUND/AIMS: As surgical morbidity and mortality for hepatocellular carcinoma
      resection decline, we would like to analyze the possible prognostic factors for
      small hepatocellular carcinoma after curative resection. METHODOLOGY: A total of
      170 patients receiving primary hepatectomies for small hepatocellular carcinoma
      (< or = 3 cm in diameter) at the National Taiwan University Hospital from
      December 1987 to February 1997 were enrolled as Group 1. The other 281 patients
      receiving hepatectomies for hepatocellular carcinoma larger than 3 cm were
      enrolled as the control group (Group 2). The overall patient and disease-free
      survival rates were calculated and the possible prognostic factors analyzed.
      RESULTS: The 1-, 3-, 5-, and 10-year patient survival rates in Group 1 were 89.6,
      73.1, 55.7 and 34.0%, respectively. A safety margin > or = 1 cm (p = 0.0283),
      single tumor (p = 0.0324), and multiple hepatic resection (p = 0.0239) were
      factors favorable to patient survival by multivariate risk factor analysis. The
      disease-free survivals for Group 1 were 75.6, 41.4, 25.9 and 19.2% at 1, 3, 5,
      and 10 years, respectively. Significant factor for better disease-free survival
      included only euploid DNA content (p = 0.0026). The patient survival and disease
      free survival rates of Group 1 were significantly better than those of Group 2.
      CONCLUSIONS: We conclude that patients with small hepatocellular carcinoma have
      better prognosis than those patients with larger tumors. Early detection of
      hepatocellular carcinoma and its recurrence are crucial for both patient and
      disease-free survival. The only prognostic factors that can be manipulated are
      the keeping of adequate safety margin and repeated resection for recurrent
      hepatocellular carcinoma.

PMID- 14696463
TI  - Surgical and interventional radiological treatment of Budd-Chiari syndrome:
      report of nine cases.
AB  - BACKGROUND/AIMS: The authors present the methods and results of treatment of
      patients with Budd-Chiari syndrome. METHODOLOGY: From a group of 15 patients with
      Budd-Chiari syndrome, treated in our department from January 1996 to September
      2001, nine patients (6 females and 3 males, aged from 23 to 45 years) were
      qualified for surgical or radiological treatment. In 3 of them the hepatic vein
      thrombosis resulted from untreated polycythemia. In the remaining 6 cases the
      etiology of thrombosis remained unknown. In four patients with dominating portal
      hypertension symptoms, a meso-caval H-type graft was created. Four patients with
      severe liver insufficiency were qualified for orthotopic liver transplantation;
      all of them were transplanted. In 1 patient a balloon dilatation of the right and
      middle hepatic veins orifices was performed during the diagnostic cavography. The
      follow-up period ranged from 4 months to 5 years. RESULTS: In 2 patients with
      Budd-Chiari syndrome of unknown etiology, the "H"-shunt remained patent, and the
      patients were free of ascites and splenomegaly. During the period of follow-up
      (more than 5 years) they remained free of symptoms and demonstrated acceptable
      liver function parameters. Doppler sonography revealed the partial recanalization
      of the venous system. In 2 polycythemic patients, the shunt thrombosed, which was
      the indication for orthotopic liver transplantation in one of them. The
      transplantation was performed, but was unsuccessful because of hepatic graft
      artery thrombosis. The retransplantation in this case was also unsuccessful. The
      remaining 3 patients transplanted for cryptogenic Budd-Chiari syndrome are alive
      and well, 4, 5 and 11 months after orthotopic liver transplantation. In the
      patient subjected to interventional radiological hepatic veins dilation, the
      vessels remain patent 26 months post-procedure. The patient is free from ascites.
      CONCLUSIONS: Shunt surgery and liver transplantation are the valuable methods of
      treatment in selected cases of Budd-Chiari syndrome. In patients with
      polycythemia, however, thrombotic complications may occur in spite of
      anticoagulant and chemotherapeutic treatment. Balloon dilatation may appear an
      alternative to surgical treatment, but it seems that its indications should be
      limited to a highly selected group of patients.

PMID- 14696464
TI  - Hepatocellular carcinoma presenting with obstructive jaundice: a
      clinicopathological study of eight cases.
AB  - BACKGROUND/AIMS: The prognosis of icteric type hepatocellular carcinoma is
      extremely poor, not only because of obstructive jaundice, but also because of
      difficulties for early diagnosis. The aim of this study is to evaluate
      characteristics of icteric hepatocellular carcinoma for early diagnosis.
      METHODOLOGY: Eight patients with icteric hepatocellular carcinoma among 326
      patients with hepatocellular carcinoma in our hospitals were retrospectively
      examined by laboratory data, image studies and pathology studies. RESULTS: Most
      cases were already advanced, with a portal tumor thrombus at the time of
      diagnosis. Imaging studies fail to reveal tumors because this type of
      hepatocellular carcinoma has an irregular faint margin and has lost the
      characteristic pattern of hepatocellular carcinoma, such as capsular formation or
      early enhancement. Pathology observations demonstrated poorly or moderately
      differentiated hepatocellular carcinoma in all our cases. CONCLUSIONS: This type
      of hepatocellular carcinoma should be considered in cirrhotic patients with
      obstructive jaundice or in patients with high tumor marker levels even if image
      studies fail to reveal tumors. For better prognosis, combination therapies such
      as biliary drainage, support for portal flow as well as treatment for the
      hepatocellular carcinoma, are necessary.

PMID- 14696465
TI  - Protective effect of IGF-1 on experimental liver cirrhosis-induced common bile
      duct ligation.
AB  - BACKGROUND/AIMS: The causes of malnutrition in liver cirrhosis are
      multifactorial. Levels of IGF-1 (insulin like growth factor-1) that is a crucial
      regulator of intermediary metabolism decreases. The aim of this study was to
      analyze the effect of IGF-1 supplementation during liver cirrhosis induced by
      common bile duct ligation. METHODOLOGY: Rats were divided into five different
      groups: One sham and four experimental groups. Rats in three of four groups were
      treated with 2 micrograms/day IGF-1 with a different time of experiment in each
      group. Blood biochemical parameters, tissue malondialdehyde, glutathione levels
      and the activity of tissue antioxidant enzymes and conventional and
      immunohistochemical analysis of liver samples were studied for each group.
      RESULTS: Serum albumin, total protein, fibrinogen levels decreased and
      prothrombin time was prolonged in the bile duct ligated and transected
      experimental group but not in the IGF-I treated rats compared with the rats in
      sham group. Liver malondialdehyde levels significantly increased in control group
      but not in IGF-1 treated groups. The activities of antioxidant enzymes were
      decreased compared with the other groups. Histopathology findings of liver biopsy
      demonstrated intense degree fibrosis and overexpression of fibroblast growth
      factor and desmin in the control group but a lesser degree of those in the IGF-1
      treated groups. CONCLUSIONS: IGF-1 treatment improves liver function and
      decreases oxidative liver damage and histopathological findings. Further studies
      are required to delineate the mechanisms of protective effects of IGF-1.

PMID- 14696466
TI  - Liver metastases from colorectal cancer: present surgical approach.
AB  - BACKGROUND/AIMS: New developments in surgical techniques and strategies are
      modifying the indications to resection of liver metastases. METHODOLOGY: From
      January 1986 to December 2000, 246 consecutive patients with colorectal liver
      metastases underwent curative hepatic resection. Surgical strategies included
      simultaneous resection of primary and metastatic colorectal tumor, re-resection
      of colorectal liver recurrences, two-stage resection and resection of the
      inferior vena cava when involved by the tumor. Disease-free survival in relation
      to clinical, pathological and surgical factors was retrospectively assessed with
      univariate and multivariate analyses. RESULTS: The overall operative mortality
      was 0.8%. The 1-, 3- and 5-year disease-free survival rates were 75%, 47% and
      40%, respectively. Tumors larger than 7 centimeters, multiple lesions, tumors
      involving more than 2 segments and those requiring major hepatectomy had a worse
      prognosis at univariate analysis. A size of the tumor above 7 centimeters was the
      only independent prognostic factors at multivariate analysis. Two-stage and
      inferior vena cava resection increased operability; re-resection of recurrent
      colorectal secondaries prolonged survival. CONCLUSIONS: Resection of colorectal
      liver metastases is safe and effective; it should be considered the treatment of
      choice for this disease and proposed even for advanced lesions. Counseling of the
      hepatobilary surgeon should be asked for once a liver secondary is detected in
      the preoperative work-up of a colorectal cancer.

PMID- 14696467
TI  - Clinical characteristics among patients with hepatocellular carcinoma according
      to the serum levels of alpha-fetoprotein and des-y-carboxy prothrombin.
AB  - BACKGROUND/AIMS: Only limited amounts of data are available at present regarding
      the clinical differences in cases of hepatocellular carcinoma who have
      seropositivity or seronegativity for AFP (alpha-fetoprotein) and DCP (des-y
      carboxy prothrombin). In the current study we investigated the different clinical
      variables in patients with hepatocellular carcinoma according to the serum levels
      of AFP and DCP. METHODOLOGY: Analyses were performed based on 168 consecutive
      patients with hepatocellular carcinoma observed for 4 years between July 1997 and
      December 2000 at the Internal Medicine Department, Saga Prefectural Hospital
      Koseikan. They were retrospectively evaluated for the analysis in the study. They
      were classified into four groups according to their serum levels of positivity
      for AFP and DCP as follows: a Negative group; seronegative for both AFP below 20
      ng/mL and DCP below 40mAU/mL, an AFP group; seropositive for AFP above 100 ng/mL
      and seronegative for DCP, a DCP group; seronegative for AFP and seropositive for
      DCP above 100mAU/mL and an AFP/DCP group; seropositive for both AFP and DCP.
      Different clinical variables were compared among the four groups. RESULTS: There
      were no significant differences among the groups regarding age, viral markers or
      the presence of underlying cirrhosis. The DCP group and the AFP/DCP group
      occurred more often in male patients and they also tended to have a higher
      incidence of large hepatocellular carcinoma measuring 3 cm or more in greatest
      dimension compared to the Negative group and the AFP group. The AFP/DCP group
      showed higher incidences of non-solitary hepatocellular carcinoma and larger
      hepatocellular carcinoma measuring 3 cm or more in greatest dimension, and the
      presence of portal thrombosis in comparison to the other three groups and also
      showed a shorter survival. CONCLUSIONS: Hepatocellular carcinomas seropositive
      for DCP were predominantly found in male patients, and hepatocellular carcinoma
      seropositive for both DCP and AFP tended to be initially diagnosed at an advanced
      stage which resulted in a shorter survival.

PMID- 14696468
TI  - Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients
      with cirrhosis: evaluation of two kinds of dosages of anticancer drugs and
      analysis of prognostic factors.
AB  - BACKGROUND/AIMS: To evaluate the efficacy of TACE (transcatheter arterial
      chemoembolization) with use of low-dose versus conventional-dose anticancer drugs
      in hepatocellular carcinoma patients with cirrhosis and to analyze their
      prognostic factors. METHODOLOGY: Eight-two patients with unresectable
      hepatocellular carcinoma underwent super-selective TACE. Patients in group A (n =
      40) received low-dose anticancer drugs. Patients in group B (n = 42) were given
      conventional-dose of anticancer drugs. Tumor response and survival time in the
      two groups were compared. Cox proportion-hazards modeling was used to evaluate
      the relative importance of prognostic variables. RESULTS: There was no
      significant difference between the two groups in initial tumor response (P <
      0.05). The median survival in all patients was 18 months (mo). The median
      survival in groups A and B were 20 mo and 16 mo respectively. The cumulative
      survival rates at 6, 12, 18, 24, 30 mo were 68.4%, 57.6%, 38.4%, 26.6%, 19.9% in
      group A, and 62.6%, 43.8%, 31.9%, 26.5%, 26.5% in group B. There was no
      significant difference in survival between the two groups (P > 0.05). The factors
      influencing prognosis were Child-Pugh scores (P < 0.0001), tumor thrombus in the
      portal vein (P < 0.0001), tumor size (P < 0.0001), method of embolization (P <
      0.0001), TACE times (P < 0.001). The dosage of anticancer drugs employed in TACE
      was not relevant to the survival rates (P = 0.883). CONCLUSIONS: TACE with use of
      large-dose anticancer drugs does not significantly enhance the anticancer effects
      and survival compared that with lowdose anticancer drugs. The therapeutic effect
      of TACE was mainly attributed to embolization of the artery rather than to
      anticancer drugs.

PMID- 14696469
TI  - Heat shock protein 70 induction in hepatocytes after right portal vein
      embolization.
AB  - BACKGROUND/AIMS: Preoperative right portal vein embolization enhances remnant
      liver function following massive hepatectomy. Several studies have reported an
      increase in the volume of the left hepatic lobe after right portal vein
      embolization, but little information exists regarding heat shock protein
      induction in hepatocytes after right portal vein embolization. The objective of
      this study is to determine whether heat shock protein is induced in hepatocytes
      after right portal vein embolization in patients who underwent extended right
      hepatic lobectomy. METHODOLOGY: Four patients with gallbladder cancer and one
      patient with intrahepatic cholangiocellular carcinoma who underwent extended
      right hepatic lobectomy combined with caudate lobectomy and resection of the
      extrahepatic bile duct after right portal vein embolization were enrolled in this
      study. Operation was performed 21-36 days after right portal vein embolization.
      At operation, small liver specimens were taken immediately after laparotomy from
      both the right anterior segment (embolized lobe) and lower part of the left
      medial segment (non-embolized lobe) and heat shock protein 70 was induction in
      these specimens was measured by Western blotting. RESULTS: Heat shock protein 70
      was induced in the left lobe relative to the right lobe in four patients, three
      of whom had an uneventful postoperative course. CONCLUSIONS: This paper is the
      first report to show the induction of heat shock protein 70 in the non-embolized
      hepatic lobe after right portal vein embolization in the clinical cases.

PMID- 14696470
TI  - Laparoscopic liver resection with radiofrequency.
AB  - BACKGROUND/AIMS: In this report, the feasibility, efficacy and safety of
      laparoscopic liver resection with radiofrequency has been evaluated in a small
      series of patients. METHODOLOGY: From January 1993 to May 2002 we carried out 7
      laparoscopic liver resections (3 men and 4 women), five of which were for benign
      pathology and two for metastases from colorectal cancer. In four of the above
      resections we used an argon coagulator; the last three were accomplished by means
      of a radiofrequency instrument. RESULTS: We had no perioperative or postoperative
      complications in this small series of patients. There were no deaths.
      Perioperative blood loss was of 120 mL (range 80-200) and the procedure took
      about 90 minutes (range 80-110). Hospitalization was of 4 days and pain was
      adequately controlled by 2 mL of Toradol twice a day. CONCLUSIONS: We think that
      the advantages of laparoscopic techniques together with the efficacy of the
      radiofrequency instrument in hepatic surgery will allow the diffusion of this
      method and its extension to safe execution of major resections.

PMID- 14696471
TI  - Association of HCV and HBV markers in Spanish HIV-seropositive patients in
      relation to risk practices.
AB  - BACKGROUND/AIMS: HBV, HCV, and HIV have some transmission routes in common. Viral
      liver disease is a leading cause of mortality in HIV-infected patients. The study
      was aimed at evaluating the prevalence of HBV and HCV markers in subjects with
      different risk practices for HIV infection. METHODOLOGY: A total of 699 subjects
      were studied Of these subjects, 517 were intravenous drug users (373 HIV-positive
      and 144 HIV-negative), 127 had heterosexual risk practice (66 HIV-positive and 61
      HIV-negative), 31 had homosexual risk practice (all HIV-positive), 15 had post
      transfusional HIV infection, and nine had HIV infection of unknown source.
      Patients with anti-HBc antibody were considered HBV-positive, and cases with anti
      HCV antibodies were considered HCV-positive. RESULTS: Among patients with HIV
      infection, most intravenous drug users (79%) had markers of both HBV and HCV,
      compared with 20%, 11%, and 10% of cases infected by transfusional, heterosexual,
      and homosexual route, respectively (p < 0.001). Absence of both HBV and HCV
      markers was observed in most HIV-positive heterosexuals (62%) compared with 40%
      of post-transfusional cases, 32% of homosexuals and 4% of intravenous drug users
      (p: NS, p = 0.009, and p < 0.001, respectively). Isolated HBV-positivity was the
      most frequent pattern in HIV-infected homosexuals (58%), compared with 27% of
      post-transfusional, 21% of heterosexuals and 11% of intravenous drug users (p:
      NS, p < 0.001 and p < 0.001, respectively). HIV-negative intravenous drug users
      had a lower prevalence of HBV/HCV association than HIV-positive cases (p <
      0.001). Isolated HCV-positivity was more frequent in HIV-negative than in HIV
      positive intravenous drug users (27% vs. 6%, p < 0.001). In heterosexuals,
      isolated HBV-positivity was more prevalent in HIV-positive than in HIV-negative
      cases (21% vs. 7%, p = 0.04). CONCLUSIONS: HBV and HCV seroprevalence in HIV
      infected patients vary depending on the risk practice. This suggests a variable
      transmissibility depending on the route considered. Within the same risk
      practice, differences in HCV and HBV seroprevalence between HIV-positive and HIV
      negative cases suggest that some factors associated with HIV infection may
      influence the rate of infection by HCV and HBV.

PMID- 14696472
TI  - Thrombolytic treatment of portal thrombosis.
AB  - BACKGROUND/AIMS: The authors present their experience with thrombolytic treatment
      of "acute" portal thrombosis. METHODOLOGY: Since 1980, portal thrombosis has been
      diagnosed in 305 patients treated in our Department. Portal thrombosis, mostly
      chronic, was associated with liver cirrhosis, Budd-Chiari syndrome, inflammatory
      and malignant liver tumors, as well as hypercoagulation conditions. In half of
      the patients the etiology of portal thrombosis remained obscure. Herewith, the
      authors present a retrospective review of 33 cases of rapidly developing portal
      thrombosis. Abdominal pain, ascites and jaundice were the most frequent initial
      symptoms. Time interval from the first symptoms appearance to hospitalization
      ranged from 8 to 60 days. The acute form of portal thrombosis was confirmed by
      Doppler sonography, spiral computed tomography and angiography. Sixteen female
      patients were regularly using oral contraceptives, in 8--portal thrombosis
      coexisted with the Budd-Chiari syndrome, in another 8--with polycythemia or
      myeloproliferative disorders and in 1 was observed during acute liver failure
      following paracetamol ingestion. RESULTS: Conservative treatment was unsuccessful
      in the first 5 cases: all of them died from esophageal variceal bleeding and
      liver failure. The next 28 patients received fibrinolytic treatment with
      streptokinase (3 cases) or recombinated tissue plasminogen activator. The results
      of therapy were evaluated on the basis of clinical picture and Doppler sonography
      monitoring. Rapid improvement of general condition, with Doppler sonography signs
      of the portal vein recanalization was noted in 10 patients, in all of whom the
      history of the disease did not exceed 14 days. In 13 patients with the longer
      history, partial portal vein occlusion persisted, but restored hepatopetal flow
      was sufficient to assure normal liver function. In the remaining 5 patients, with
      the history of the disease lasting longer than 30-40 days, the treatment failed
      and no clinical or Doppler sonography evidence of restoring of the portal flow
      were demonstrated. Four patients died: 2 from portal rethrombosis, 1 from liver
      failure and 1 from cerebral stroke (12, 16 months, 3 months and 4 years after
      therapy, respectively). Twenty-four patients are alive, the time of follow-up
      ranging from 9 months to 6 years. In 8 cases, five years after portal system
      recanalization the first symptoms of portal hypertension occurred. CONCLUSIONS:
      Thrombolytic treatment of acute portal thrombosis, if administered promptly,
      appears to be the only way to improve, or even restore, the portal system
      patency.

PMID- 14696473
TI  - Prognosis of patients with a diagnosis of fatty liver--a registry-based cohort
      study.
AB  - BACKGROUND/AIMS: There are very limited data available regarding the prognosis of
      patients with fatty liver. We examined the overall and cause-specific mortality
      of fatty liver patients in a large Danish cohort. METHODOLOGY: In the Danish
      National Registry of Patients, we identified 7,372 patients discharged with a
      diagnosis of fatty liver from a Danish hospital between 1977 and 1993. Causes of
      death were identified in the Danish Death Registry. We estimated the standardized
      mortality ratio by comparing with the general population. RESULTS: Most patients
      (76%) had alcoholic fatty liver. During follow-up, 2,914 (40%) died. The
      commonest cause of death was hepatobiliary disease (25% of deaths). Mortality was
      increased 5.4-fold (95% CI 5.2-5.6) in patients with alcoholic fatty liver, and
      2.6-fold (95% CI 2.4-2.9) in patients with non-alcoholic or unspecified fatty
      liver. Overall, in the first year of follow-up, mortality was increased more than
      7-fold, almost 5-fold in the second to fifth years, and more than 3-fold after
      that. Mortality was similar among genders and among diabetics and non-diabetics,
      and remained increased after censoring patients upon diagnosis of liver
      cirrhosis. CONCLUSIONS: The mortality of patients with a hospital discharge
      diagnosis of fatty liver was higher than that of the general population.

PMID- 14696474
TI  - Treatment of chronic hepatitis B with high-dose intravenous N-acetyl-L-cysteine.
AB  - BACKGROUND/AIMS: Therapy of hepatitis B with alpha-interferon is only successful
      in 30-40%; therefore new therapeutic options are needed. N-acetyl-L-cysteine is
      well known as an antidote against paracetamol intoxication and as mucolytic agent
      in pulmonary diseases. Furthermore, it restrains human immunodeficiency virus
      replication and inhibits hepatitis B virus replication at a posttranscriptional
      level in vitro. This study aims to evaluate the efficacy of N-acetyl-L-cysteine
      in 5 patients chronically infected with hepatitis B virus. METHODOLOGY: N-acetyl
      L-cysteine was given intravenously at a daily dose of 150 mg/kg body weight.
      Treatment was performed for 28 days. RESULTS: The N-acetyl-L-cysteine infusions
      were tolerated without any side effects. Except a mild increase in thrombocyte
      counts within the last week of N-acetyl-L-cysteine infusion blood tests did not
      change. We could not detect any changes in quantitative hepatitis B virus-DNA
      levels as well as in the HBeAg-status. CONCLUSIONS: We conclude from our data
      that N-acetyl-L-cysteine given in a high dose intravenously for 28 days is well
      tolerated. In contrast to in vitro studies no significant effects on the
      hepatitis B-virus load were detectable in vivo.

PMID- 14696475
TI  - Surgical treatment of liver trauma (analysis of 244 patients).
AB  - BACKGROUND/AIMS: The liver is the most common injured intraabdominal organ after
      trauma. This retrospective study was designed to analyze the results of the
      surgical treatment of 244 cases of liver trauma operated between 1973 and 2001.
      METHODOLOGY: Two hundred and seventeen of the cases were male and 27 were female.
      Mean age of the patients was 29.6. Blunt injuries were responsible for liver
      trauma in 53.6% of the patients. According to the American Association for the
      Surgery of Trauma classification we evaluated the patients to two groups. The
      first one was Group A, minor hepatic injuries, which consisted of grade I, grade
      II and grade III injuries, and the second one was Group B, major hepatic
      injuries, which consisted of grade IV, grade V and grade VI injuries. There were
      238 cases in Group A and 6 cases in Group B. Primary suturing of the hepatic
      rupture was performed in 187 of 238 cases in group A. Liver injuries of the other
      50 cases did not require suturing so that we drained the suprahepatic and
      infrahepatic spaces during laparotomy. The remaining case in group A had
      resectional debridement and hemostasis. On the other hand we performed regular or
      irregular hepatic resection in all group B patients. RESULTS: Overall mortality
      rate was 16.3%. The mortality rate was higher in group B than group A (66.6% and
      15.1%, respectively). The mortality rate was also higher in the blunt abdominal
      trauma cases than penetrating injuries (25.9% and 5.3% consecutively).
      CONCLUSIONS: We concluded that the injury grade and the type of trauma influence
      the mortality rate. Careful clinical assessment and close radiological monitoring
      of the patients with minor hepatic injuries, may prevent unnecessary
      laparotomies.

PMID- 14696476
TI  - A pilot study of combination therapy with initial high-dose interferon and
      amantadine hydrochloride for patients with chronic hepatitis C with the genotype
      1b virus.
AB  - BACKGROUND/AIMS: Interferon monotherapy for patients with chronic hepatitis C has
      been suboptimal. We studied the effect of the combination therapy of an initial
      high-dose of interferon and amantadine. METHODOLOGY: We investigated the
      virological response of 20 patients with naive chronic hepatitis C with a high
      viral load of the genotype 1b virus. Seven patients were administered 6MU of
      interferon-beta once daily for 6 weeks and then thrice weekly for 20 weeks, and
      13 were administered 6 MU of interferon-beta daily for 4 or 6 weeks and then 10
      MU of natural interferon-alpha thrice weekly for 22 or 20 weeks. All patients
      were treated with amantadine hydrochloride (100 mg/day) for 26 weeks during
      interferon administration. RESULTS: The complete response, transient response and
      no response rate were 15.0%, 60.0%, and 25%, respectively. After daily
      administration of interferon-beta intravenously, 19 patients (95.0%) showed
      negative tests for serum HCV-RNA by the polymerase chain reaction method. At the
      end of treatment, the serum HCV-RNA was not detected in any patients treated with
      daily interferon-beta and intermittent interferon-alpha with amantadine. At 6
      month follow-up, three patients had eradicated HCV-RNA, who were in the group of
      daily interferon-beta and intermittent interferon-alpha with amantadine. In the
      patients treated with daily interferon-beta and intermittent interferon-alpha
      with amantadine, the complete response, transient response and no response rates
      were 23.1%,-76.9% and 0%, respectively. CONCLUSIONS: These findings suggest that
      the combination of an initial high-dose interferon and amantadine shows promising
      effects on the eradication of HCV-RNA in the chronic hepatitis C patients with a
      high viral load of the genotype 1b virus.

PMID- 14696477
TI  - Oxygen metabolism of the liver during an HA clamp: HV saturation and free
      radicals.
AB  - BACKGROUND/AIMS: To clarify changes in the hepatic oxygen metabolism and tissue
      damage resulting from oxygen-derived free radical generation from
      polymorphonuclear cells during a hepatic arterial clamp. METHODOLOGY: Subjects
      were 32 male Wistar rats. Hepatic tissue blood flow, and hepatic venous
      chemiluminescence, indicating oxygen-derived free radicals from polymorphonuclear
      cells, and liver lipid peroxide were measured, and hepatic and portal venous
      blood gas analysis were performed before and after 130 minutes of hepatic
      arterial clamping. RESULTS: Hepatic tissue blood flow decreased by hepatic
      arterial clamp. The values of hepatic arterial oxygen pressure (HTBF), hepatic
      venous oxygen saturation (ShvO2), and O2 contents after hepatic arterial clamp
      were lower than those before hepatic arterial clamp (P = 0.035, 0.024, and 0.028,
      respectively). Hepatic venous chemiluminescence decreased and the lipid peroxide
      level of the liver increased by hepatic arterial clamp (P = 0.001). CONCLUSIONS:
      ShvO2 is useful for the evaluation of hepatic oxygen metabolism and hepatic
      tissue blood flow during acute hepatic arterial clamp. This condition should
      prepare the following tissue damage due to oxygen-derived free radicals from
      polymorphonuclear cells.

PMID- 14696478
TI  - Serum immunoglobulins (IgG, IgA, IgM) in chronic hepatitis C. A comparison with
      non-cirrhotic alcoholic liver disease.
AB  - BACKGROUND/AIMS: Serum immunoglobulin concentrations are commonly elevated in
      patients with liver cirrhosis. Immunoglobulin class increase may vary depending
      on the cause of liver disease. Hepatitis C virus is, together with alcohol, a
      leading cause of chronic liver disease. The present study aimed to evaluate serum
      IgG, IgA and IgM levels in chronic hepatitis C. Results were compared with those
      of patients with non-cirrhotic alcoholic liver disease and healthy controls.
      Special attention was given to cases with minimal liver disease, as an approach
      to evaluate if the causing agent, independently of liver damage, influences serum
      immunoglobulin levels. METHODOLOGY: A total of 274 patients with histologically
      proven chronic hepatitis C, 121 alcoholics with non-cirrhotic liver disease
      (steatosis or alcoholic hepatitis), and 75 healthy controls were studied. Serum
      IgG, IgA, and IgM were assayed by nephelometry. RESULTS: Serum IgG was increased
      in patients with chronic hepatitis C with respect to both alcoholics (p < 0.001)
      and healthy controls (p < 0.001). IgG levels were similar in alcoholics and in
      controls. IgA was increased in patients with non-cirrhotic alcoholic liver
      disease with respect to both chronic hepatitis C patients (p < 0.001) and
      controls (p < 0.001). IgA values were similar in subjects with chronic hepatitis
      C and controls. Selective IgG or IgA alteration was present in cases with minimal
      liver disease (chronic hepatitis C with a Knodell index equal or lower than 3,
      and alcoholics with liver steatosis, respectively). CONCLUSIONS: Hepatitis C
      virus and alcohol are linked to a selective increase of serum IgG and IgA,
      respectively, even in cases with mild or minimal liver disease.

PMID- 14696479
TI  - Comparison of the effects of continuous and intermittent portal triad occlusion
      (PTO) in rats.
AB  - BACKGROUND/AIMS: It has previously been shown that prolonged ischemia of the
      liver had a mortal course and a method of intermittent occlusion of the hepatic
      pedicle was defined in order to minimize the damage to the liver. The present
      experimental study aimed to compare the effects of continuous and intermittent
      occlusion of the hepatic pedicle on the liver by measuring serum lactate, serum
      MDA malondialdehyde and glutathione levels and by evaluating the histologic
      changes in the liver tissue. METHODOLOGY: Thirty male Wistar albino rats weighing
      300 +/- 50 g were divided into three groups of ten animals. Group 1 underwent a
      sham operation. Animals in group 2 underwent continuous portal triad occlusion
      (PTO group) for 30 minutes following laparotomy. The remaining ten animals in
      group 3 underwent intermittent occlusion consisting of 10 minutes of occlusion
      followed by 10 minutes of reperfusion for a total period of 30 minutes of
      ischemia. Blood samples were collected at the 1st and 6th postoperative hour for
      analytical evaluation. After sacrificing the animals, liver samples were obtained
      for histologic evaluation. RESULTS: The serum lactate levels were significantly
      higher in both portal triad occlusion groups than in the control at the 1st hour.
      While lactate levels also increased at the 6th hour in the continuous PTO group,
      it decreased to the level of control values in the intermittent PTO group. The
      difference between continuous and intermittent groups was also significant.
      Despite the unchanged malondialdehyde levels in the control group,
      malondialdehyde levels were significantly increased at the first and sixth hour
      in both PTO groups and the levels were also significantly higher than control
      values. Malondialdehyde levels of intermittent PTO groups at the first and sixth
      hour were both significantly lower than continue PTO groups. Whole blood
      glutathione levels were not changed in control groups with time, levels increased
      significantly in both PTO groups. Glutathione levels were higher than control
      values in both PTO groups at the first hour. While it turned to its basal value
      in intermittent PTO groups at the 6th hour, it was still significantly higher in
      the continuous PTO group. When both PTO groups were compared, glutathione levels
      were found to be significantly higher in the continuous group both at the first
      and sixth hour than in the intermittent PTO group. Histopathologic evaluation
      also showed that there was less damage in the intermittent PTO group than in the
      continuous PTO group. CONCLUSIONS: Our results show that continuous portal triad
      occlusion resulted in significant oxidative stress and cell damage as confirmed
      by increased serum lactate and blood malondialdehyde levels. The blood
      glutathione levels are increased due to a greater requirement in response to
      increased oxidative stress induced by portal triad occlusion. It is also
      confirmed that intermittent portal triad occlusion is safer as it causes less
      oxidative stress and cell damage so that its use is strongly suggested whenever
      portal triad occlusion is required.

PMID- 14696480
TI  - Prognosis of patients with liver cirrhosis and spontaneous bacterial peritonitis.
AB  - BACKGROUND/AIMS: Patients with liver cirrhosis and ascites have a high risk of
      spontaneous bacterial peritonitis, but the prognostic impact of spontaneous
      bacterial peritonitis has not been well examined. METHODOLOGY: Patients with
      liver cirrhosis and ascites were included at the time of their first paracentesis
      during hospitalization in the Department of Hepatology, Aarhus University
      Hospital, Denmark, between September 1992 and September 2000. Cox regression was
      used to estimate the mortality of patients with spontaneous bacterial peritonitis
      (ascites leukocyte count > or = 250 per mm3) relative to controls without
      spontaneous bacterial peritonitis. Furthermore, we used Cox regression to
      estimate the change in mortality when controls developed spontaneous bacterial
      peritonitis during follow-up. RESULTS: Of 286 patients, 76 (27%) had spontaneous
      bacterial peritonitis at the first paracentesis. The mortality ratio of patients
      with spontaneous bacterial peritonitis relative to controls was 1.0 (95%
      confidence interval 0.7-1.5) after adjustment for age, gender, comorbidity, and
      alcohol abuse. Of the 210 controls, 42 (20%) were found to have spontaneous
      bacterial peritonitis at a later paracentesis. Their mortality rate more than
      doubled with the onset of spontaneous bacterial peritonitis. CONCLUSIONS:
      Spontaneous bacterial peritonitis at the first paracentesis did not affect the
      prognosis of patients with liver cirrhosis, whereas development of spontaneous
      bacterial peritonitis during follow-up doubled the mortality risk. This may be
      due to a longer diagnostic delay in those who developed spontaneous bacterial
      peritonitis during follow-up.

PMID- 14696481
TI  - Sister chromatid exchange and mitotic index in patients with cirrhosis related to
      hepatitis B and C viruses and in chronic carriers.
AB  - BACKGROUND/AIMS: It is controversial whether hepatitis B or C viruses induce
      liver cancer through non-specific mechanisms (inflammation and cell renewal) or
      direct genotoxicity. Considering that both viruses infect peripheral lymphocytes,
      studying sister chromatid exchange frequency and mitotic index in peripheral
      lymphocytes is a reasonable experimental approach to investigate their genotoxic
      potential separately. In the present study we investigated sister chromatid
      exchange frequency and mitotic index in the peripheral lymphocytes of patients
      with cirrhosis and chronic carriers with positive serology for HBV or HCV
      infections. METHODOLOGY: The study population consisted of 3 groups: group I
      involved 23 HBsAg positive chronic carriers; group II involved 30 HBsAg positive
      patients with cirrhosis and group III involved 9 HCV-positive patients with
      cirrhosis. The control group involved 30 healthy individuals. RESULTS: Sister
      chromatid exchange frequency was significantly higher in all the study groups
      than the control group (p < 0.05). The mitotic index was significantly lower in
      all the study groups than the control group (p < 0.05). CONCLUSIONS: The
      increased sister chromatid exchange frequency and low mitotic index may be
      reflecting a direct genotoxic effect of HBV and HCV in peripheral lymphocytes. We
      suggest that the same genotoxicity may also operate in the liver and contribute
      to hepatocarcinogenesis.

PMID- 14696482
TI  - Usefulness of biodegradable absorbable rib connecting pins in thoracoabdominal
      hepatectomy.
AB  - BACKGROUND/AIMS: Some patients who undergo thoracoabdominal hepatectomy suffer
      from pain and discomfort after because rib and/or costal cartilage was cut during
      the operation. The usefulness of absorbable rib connecting pins in
      thoracoabdominal hepatectomy was evaluated. METHODOLOGY: Of 18 patients who
      underwent thoracoabdominal hepatectomy, the stumps of ribs were not fixed in 9
      patients (group 1) and the stumps of ribs were fixed with the rib connecting pins
      in 9 other patients (group 2). We evaluated the usefulness of these pins in
      thoracoabdominal hepatectomy. RESULTS: In 8 patients in group 1 and 2 patients in
      group 2, pain continued for 1 month after the operation (p = 0.015). At 2 months
      after the operation, pain continued in 6 patients in group 1 and no patients in
      group 2 (p = 0.009). At 6 months after the operation, 2 patients in group 1 still
      had pain. Rib instability continued in 8 patients in group 1 at 6 months after
      the operation, although rib instability disappeared by 2 months after the
      operation in all group 2 patients (p = 0.0004). CONCLUSIONS: Biodegradable
      absorbable pins for rib fixation are useful for preventing pain and discomfort
      around the cut stumps of ribs in thoracoabdominal hepatectomy.

PMID- 14696483
TI  - Liver recipients undergoing hepatic transplantation and subsequent
      retransplantation: a comparison between clinical characteristics.
AB  - BACKGROUND/AIMS: In order to establish a rational strategy for organ distribution
      and optimal patient management, we postulate it is mandatory not only to
      understand the pathophysiology of failing grafts but also to better recognize the
      baseline clinical characteristics of the recipients shortly before receiving a
      second liver allograft. METHODOLOGY: Between March 1986 and December 1997, 1061
      patients underwent 1087 orthotopic liver transplantation at three Hospitals in
      Madrid (122 retransplants). RESULTS: Mean follow-up was 36 months (range, 1-90),
      40.6% of the recipients were alive and survival at 1, 3 and 5 years was 62%, 53%,
      and 46%. Almost 50% of the recipients were UNOS 1 before retransplantation. In
      comparison to p-OLT (15% UNOS 1), it is clearly shown that the retransplants have
      been performed in the sickest patients with more adverse prognostic indicators
      (higher AST, bilirubin, creatinine serum levels, higher Child-Pugh score, higher
      rate of ascites and lower serum levels of albumin and prothrombin activity).
      CONCLUSIONS: Liver retransplantation is acceptable and significant differences in
      recipients' baseline characteristics suggest an impact on lower survival.

PMID- 14696484
TI  - MR and 1H MR spectroscopy of the brain in patients with liver cirrhosis and early
      stages of hepatic encephalopathy.
AB  - BACKGROUND/AIMS: Hepatic encephalopathy is a serious problem in patients with
      liver cirrhosis and precise pathophysiological mechanisms responsible for
      encephalopathy are not fully understood. Magnetic resonance imaging and magnetic
      resonance spectroscopy can be used to detect specific morphological and metabolic
      abnormalities in the brain even in patients with early stages of hepatic
      encephalopathy. METHODOLOGY: Twenty patients with liver cirrhosis and 14 patients
      with grade I-II hepatic encephalopathy were studied with magnetic resonance and
      proton magnetic resonance spectroscopy. Localized magnetic resonance spectra were
      acquired in the parietal gray/white matter regions and basal ganglia. Control
      group consisted of 20 healthy volunteers. RESULTS: Frequency and degree of brain
      atrophy and bilateral signal hyperintensities in globus pallidus were similar in
      groups with liver cirrhosis and with encephalopathy. Decreased myoinositol,
      choline and increased glutamine levels were noted in both groups whereas N
      acetylaspartate levels were unchanged. The statistically significant differences
      between cirrhotic and encephalopathic groups were observed only in
      myoinositol/creatine ratio in basal ganglia. There were no significant
      differences in metabolic concentrations between parietal and basal ganglia
      regions. CONCLUSIONS: Metabolic brain alterations occur earlier than clinical
      evidence of hepatic encephalopathy but there is no correlation between presence
      of symptoms encephalopathy and magnetic resonance and magnetic resonance
      spectroscopy findings.

PMID- 14696485
TI  - Limited value of 18F-2-deoxyglucose positron emission tomography to detect
      hepatocellular carcinoma in hepatitis B virus carriers.
AB  - BACKGROUND/AIMS: The differentiation of hepatocellular carcinoma from benign
      liver diseases in hepatitis B virus carriers by imaging studies based upon
      morphological aspects can be difficult. METHODOLOGY: FDG-PET (18F-2-deoxyglucose
      positron emission tomographies) were performed in 48 hepatitis B virus carriers
      to detect hepatocellular carcinoma and differentiate other benign liver diseases.
      In each patient, the focal liver lesion was visible by ultrasound and an elevated
      serum alpha-fetoprotein level was noted. Definite diagnosis was established after
      ultrasound-guided liver biopsy followed by histopathological examination.
      RESULTS: The histopathological examination revealed hepatocellular carcinoma in
      36 patients and benign liver diseases in the remaining 12 patients. Twenty of 36
      hepatocellular carcinomas were detectable by FDG-PET and none of 12 benign liver
      diseases were visualized by FDG-PET. The detection sensitivity of FDG-PET was not
      related to the echogenicity and size of hepatocellular carcinoma. CONCLUSIONS:
      FDG-PET is not sensitive to but is more specific than ultrasound and serum alpha
      feto-protein level to detect hepatocellular carcinoma and differentiate from
      other benign liver diseases in hepatitis B virus carriers.

PMID- 14696486
TI  - Clinical features of patients with HCC who are negative for both HBV and HCV
      markers.
AB  - BACKGROUND/AIMS: The aim of this study is to clarify the clinical features of
      hepatocellular carcinoma that are negative for both hepatitis B surface antigen
      and anti-hepatitis C antibody. METHODOLOGY: Patients were classified according to
      viral markers: 45 patients (82%) had hepatitis B (B-HCC), 467 patients (82%) had
      hepatitis C (C-HCC), and 53 patients (9%) had neither hepatitis B nor hepatitis C
      (NBNC-HCC). Differences in clinical parameters among these three groups were
      analyzed. RESULTS: Patients with NBNC-HCC were older than B-HCC and C-HCC
      patients. The incidence of alcoholism in NBNC-HCC patients was higher than in C
      HCC patients. Patients with NBNC-HCC had similar rates of positive antibody to
      hepatitis B core antigen as did patients with C-HCC. NBNC-HCC patients were
      further classified according to median age. The younger group showed a greater
      tendency towards alcoholism than did the aged group. Liver functioning in the
      younger group was worse than in the older group. The older group had larger
      tumors than the younger group. CONCLUSIONS: The livers of younger NBNC-HCC
      patients were more cirrhotic, possibly because of alcoholism. Older NBNC-HCC
      patients presented with larger tumors, possibly because they did not receive
      regular medical check-ups due to their relatively preserved liver function.

PMID- 14696487
TI  - Macrochimerism of donor type CD56+ CD3+ T cells in donor specific transfusion via
      portal vein following living related donor liver transplantation.
AB  - Antigens given orally or through the portal vein are known to be less immunogenic
      and to induce immunologic unresponsiveness. The mechanisms responsible for graft
      enhancement are still unclear. Moreover, in actuality, it is difficult to perform
      transfer of donor antigens via the portal vein in clinical transplantation. We
      investigated the effect of transfer of donor blood via the portal vein intra- and
      post-operatively in living related donor liver transplantation for recurrent
      multiple hepatocellular carcinoma. A 62-year-old female, who suffered from
      recurrent multiple hepatocellular carcinoma with hepatitis C virus, underwent
      living related donor liver transplantation with the right lobe of her daughter.
      Eleven hepatocellular carcinomas were recognized in the resected specimen. Donor
      blood was administered via the portal vein using a catheter inserted in the
      middle colic vein intra- and postoperatively. Mononuclear cells were obtained by
      operative liver biopsy or postoperative biopsy using fine needle aspiration
      biopsy, and from peripheral blood. They were analyzed by two or three color-flow
      cytometry using several antibodies. The differentiation between donor and
      recipient was estimated by means of anti-HLA antibodies of donor and recipient.
      The postoperative course was uneventful. She did not suffer from acute cellular
      rejection and was discharged on day 30 the after operation. CD56+ CD3+ T cells in
      the liver increased notably from 20% to 50% after transplantation. One half of
      the CD56+ CD3+ T cells in the liver graft were of the donor type (donor anti-HLA
      A2 antibody) on day 8 after surgery. Donor type CD56+ CD3+ T cells occupied 17.4%
      of the total CD56+ CD3+ T cells even on day 42 after the operation. Stimulation
      index by mixed lymphocyte reaction continued at a low level (< 2) from day 1
      after the operation. Steroids were discontinued after 40 postoperative days.
      FK506 was also reduced to 0.5 mg/day 4 months after the operation. There was no
      recurrence of hepatocellular carcinoma and hepatitis C virus for two years after
      the operation. Macrochimerism of donor type CD56+ CD3+ T cells in a graft might
      be induced by the transfer of donor blood via the portal vein and may play an
      important role in transplantation tolerance. Inoculation of donor blood via the
      portal vein may also be very useful for rapid reduction of immunosuppression.

PMID- 14696488
TI  - Pancreatic carcinoid: transcatheter arterial chemoembolization of liver
      metastases.
AB  - Carcinoid tumors are a common disease in the gastrointestinal tract, but are
      extremely rare in pancreas. To our knowledge, only 33 carcinoid tumors of
      pancreas have been reported in the English literature. Complete surgical
      resection of pancreatic carcinoid contributes to prolonged survival. But distant
      metastases, including liver metastasis, prevent long-term survival. We report
      here one resected case of pancreatic carcinoid tumor with liver metastases.
      Postoperatively, multiple liver metastases had arisen in the bilateral lobe of
      the liver and were treated with transcatheter arterial chemoembolization. In this
      case, transcatheter chemoembolization was effective for palliation for
      postoperative liver metastases.

PMID- 14696489
TI  - Hepatic autotransplantation with ex situ neoplasm extirpation and vena cava
      replacement.
AB  - The treatment of a 64-year-old man with a retrohepatic neoplasm deemed not
      accessible by conventional in situ surgical techniques is presented to illustrate
      the potential benefit offered by techniques adapted from liver transplantation
      and vascular surgery. A computed tomography scan performed for uncharacteristic
      abdominal discomfort revealed a hepatic or retrohepatic tumor compressing the
      inferior vena cava. Biopsies were interpreted as probably leiomyoma or malignant
      schwannoma. The liver with neoplasm and retrohepatic inferior vena cava was
      removed en bloc and taken to the back table where the neoplasm invading the
      inferior vena cava wall was removed together with the inferior vena cava. The
      inferior vena cava was then replaced by a 22-mm polytetrafluoroethylene graft and
      the 3 hepatic veins were reconstructed with anastomoses to this graft. The liver
      was then autotransplanted by standard transplantation technique. The
      postoperative course was uneventful and the patient is in good health more than 2
      years after surgery.

PMID- 14696490
TI  - Hepatectomy with transcatheter arterial embolization for large hepatoma in the
      caudate lobe.
AB  - The prognosis of hepatocellular carcinoma originating from the caudate lobe
      (caudate HCC) is generally poor, and surgical treatment for caudate HCC is
      difficult to perform due to the location. We postulate that a combination of
      surgical resection and transcatheter arterial embolization improves the
      prognosis, and that operative procedure is straightforward. We examined three
      cases of large solitary caudate HCC. Three patients (a 68-year-old woman, 65-year
      old man, and 71-year-old man) with caudate HCC and viral chronic hepatitis were
      treated with preoperative transcatheter arterial embolization and partial
      resection of the caudate lobe. After transcatheter arterial embolization, the
      solitary hepatocellular carcinomas decreased in size (9 to 6, 10 to 8, and 7 to 5
      cm in diameter, respectively) which simplified surgical resection (1120, 3010,
      and 2110 cc blood loss; 4.5, 7, and 7 hours of operative time, respectively). All
      the hepatocellular carcinomas were poorly differentiated, and had infiltrated
      microscopically into the portal vein. The outcome was satisfactory (18, 16, and
      10 months after the operation, two cases were alive, and one dead, respectively).
      The combination of preoperative transcatheter arterial embolization and partial
      resection for caudate HCC, especially large solitary caudate HCC, works well as a
      multimodal therapy.

PMID- 14696491
TI  - Near total hepatectomy in two steps for surgical treatment of liver metastasis of
      colorectal tumor.
AB  - Liver resections for metastases of colorectal carcinomas are generally accepted.
      The 5-year survival rate is higher than 30 percent. Major resections can be
      performed safely with normal remnant liver. The liver regenerates following
      extended hepatectomies or other major resections. Authors operated on a 57-year
      old man for a secondary liver tumor. The primary tumor was in the colon
      sigmoideum and sigma-resection was made at another hospital 16 months before. The
      metastasis was in the right lobe of the liver. Authors performed right extended
      hepatectomy. After systemic chemotherapy, 4.5 months later a new metastasis
      developed in the left lobe. Despite locoregional chemotherapy, chemoembolization
      and radiofrequency treatment, the tumor was still growing so a left lobectomy was
      performed. The patient is macroscopically tumor-free 17 months after the first
      hepatic resection. The interest in this case is that segments IV to VIII were
      removed first time, and segments II and III at the second liver resection. Liver
      regeneration after the first resection made the second operation possible. Only
      segment I of the original segments remained. Utilizing the regeneration of the
      liver we can make an effort to perform a complete tumor ablation in two steps.

PMID- 14696492
TI  - Aggressive recurrence after radiofrequency ablation of liver neoplasms.
AB  - Radiofrequency ablation is considered safe for inoperable liver neoplasms; with
      small lesions the rate of success is very high, the local recurrence is marginal
      and generally suitable for a retreatment. We have little information about the
      possibility of rapid regrowth of the tumor after a response judged as complete.
      We present four patients, affected by primary (3 patients) and metastatic (1
      patient) uninodular cancer. All the lesions were small, superficial and well
      suited for surgery, but were treated by radiofrequency ablation elsewhere. The
      early instrumental evaluations stated a complete result in all the patients.
      Cancer regrowth was diagnosed at 3, 4, 6 and 12 months after radiofrequency
      ablation, always starting from the treated lesion. In case 1 the whole right lobe
      was involved together with a controlateral multinodular recurrence; cases 2 and 3
      presented an extensive liver and parietal wall involvement; while in the fourth
      patient a diffuse biliary colonization was observed. Only 1 patient was suitable
      for surgery; the others died 6, 2 and 4 months, respectively, after recurrence.
      Recurrence after radiofrequency ablation may show an aggressive evolution
      precluding any possibility of cure. Radiofrequency ablation must not be
      considered a suitable alternative to surgery in patients with a low surgical
      risk.

PMID- 14696493
TI  - Monolobar Caroli's disease in an adult. Case report.
AB  - Caroli's disease is the dilatation of the segmental intrahepatic bile ducts which
      generally presents in a diffuse form, but may occasionally involve only a single
      lobe, commonly the left one. We report the case of a 64-year-old male who
      presented with a clinical picture of obstructive jaundice, with Caroli's disease
      in segments II and III of the liver. Preoperative diagnosis was made using
      abdominal ultrasound and computed tomography scan, confirmed by endoscopic
      retrograde cholangiopancreatography. The treatment used was segmentectomy II and
      III (left lobectomy--Couinaud's classification) of the liver. Macroscopic
      examination of the resected specimen revealed cystic dilatation of the
      intrahepatic bile ducts and intrahepatic lithiasis. Histologically there was no
      evidence of malignancy. Liver resection is the treatment of choice for Caroli's
      disease confined to a single lobe or segment, eliminating the potential for
      cholangitis, lithiasis and carcinoma.

PMID- 14696494
TI  - Inferior vena cava thrombosis: an unusual complication of a large simple non
      parasitic liver cyst requiring an integrated approach.
AB  - Most of the simple hepatic cysts are asymptomatic and have a benign course.
      However, some exceptional life-threatening complications may occur. We herein
      report the successful management of a case who suffered from a cystic compression
      of the inferior vena cava complicated by thrombosis of the inferior vena cava
      itself. To our knowledge this is the first report of such a complication and
      diagnostic and therapeutic aspects are discussed. This case is paradigmatic of
      the possible complexity of the diagnosis and treatment of cystic lesions of the
      liver and should induce physicians to consider a therapeutic approach if a clear
      tendency to enlarge can be recognized.

PMID- 14696495
TI  - Refractory acute rejection in a living related liver transplantation.
AB  - Hepatic allograft rejection after liver transplantation remains an important
      problem. We report a case of corticosteroid and anti-T cell monoclonal antibody
      resistant acute cellular rejection in living related liver transplantation. A 57
      year-old female received a right liver graft from her daughter for hepatitis C
      related liver cirrhosis. Methylprednisolone and tracrolimus were used for
      immunosuppression. The patient experienced acute rejection 10 days after the
      operation. Rescue therapy was attempted using high doses of methylprednisolone
      and then monoclonal antibodies. Deterioration of graft function, however, was not
      prevented, resulting in graft and patient loss. Graft lost due to refractory
      acute rejection could also occur in living related liver transplantation,
      although it should be rare.

PMID- 14696496
TI  - Mucin-producing intrahepatic cholangiocarcinoma with portal vein thrombosis.
AB  - Mucin-producing intrahepatic cholangiocarcinoma is rare. Computed tomographic
      scan and magnetic resonance imaging showed a well-defined tumor with marked
      dilatation of the left intrahepatic bile duct and portal vein thrombosis. We
      performed extended left hepatectomy and portal vein thrombectomy. A massive
      amount of mucin was observed in the left intrahepatic bile duct. Histological
      examination revealed noninvasive and well differentiated tubular adenocarcinoma.

PMID- 14696498
TI  - Delayed massive arterial hemorrhage after pancreaticoduodenectomy for cancer.
      Management of a life-threatening complication.
AB  - BACKGROUND/AIMS: Delayed massive arterial hemorrhage from the operating field
      occurs in 1-4% of cases after pancreaticoduodenectomy, with a mortality rate up
      to 50%. The purpose of this study was to define diagnostic and treatment
      methodologies to maximize survival. METHODOLOGY: Between 1990 and 1999, 84
      pancreaticoduodenectomies were performed for periampullary and pancreatic head
      cancer. After surgery, massive bleeding occurred in two patients (2.3%), 30 and 8
      days after resection, respectively. RESULTS: Pancreatic leak and disruption of
      the pancreaticojejunostomy were reported in both cases. Bleeding was controlled
      by suture ligation of the stump of the gastroduodenal artery. Completion
      pancreatectomy and a new pancreaticojejunostomy were respectively performed.
      Hemorrhage recurred in both cases from a ruptured pseudoaneurysm of the hepatic
      artery, requiring re-exploration and surgical ligation. The first patient died of
      re-bleeding despite completion pancreatectomy, the other survived after
      oversewing the residual pancreatic stump at re-exploration. CONCLUSIONS: Early
      diagnosis and management of pancreatic leak represents the only means to prevent
      a delayed massive arterial hemorrhage. Transarterial embolization or surgical
      ligation of the hepatic artery proximal to the celiac axis represents the
      procedure of choice to control the bleeding. Taking down the pancreatic
      anastomosis and oversewing the pancreatic stump is safe and effective. Extensive
      drainage of the operating field should always be associated to prevent
      multisystem organ failure.

PMID- 14696499
TI  - Considerations on early diagnosis of carcinoma of the pancreas.
AB  - BACKGROUND/AIMS: Pancreas carcinoma is seldom recognized at an early stage.
      Through an attentive retrospective evaluation of the patient's history a frequent
      pattern of early presentation is sought. METHODOLOGY: A series of 64 patients (36
      males; 28 females) with histologically proven pancreas carcinoma seen in the
      Department of Surgery and the Oncology Department of the University of Milan
      (Ospedale "L. Sacco") in the years 1992 through 2001, is closely scrutinized,
      tracing the very initial signs and symptoms in each individual case. RESULTS:
      Weight loss is by far the most frequent early complaint, being the presenting
      symptom in more than 79% of cases, either alone or associated with one or more
      additional symptoms, followed by pain (56%), anorexia (28%), jaundice (25%) and
      asthenia (23%). However it appears that weight loss is often overlooked until
      other more suggestive symptoms ensue. In particular, slowly developing jaundice
      was the most common indication for ultrasound scan or computed tomography study,
      although jaundice was the presenting symptom in only 25% of cases. CONCLUSIONS:
      In patients presenting with unexplained weight loss, a more liberal use of
      diagnostic imaging techniques in the upper abdomen might be advisable.

PMID- 14696497
TI  - Clinical significance of the accessory pancreatic duct.
AB  - BACKGROUND/AIMS: The accessory pancreatic duct is the smaller and less constant
      pancreatic duct in comparison with the main pancreatic duct. We investigated the
      patency of the accessory pancreatic duct and its role in pancreatic
      pathophysiology. METHODOLOGY: Dye-injection endoscopic retrograde pancreatography
      was performed in 411 patients. In patients in whom the main pancreatic duct could
      be selectively cannulated, contrast medium with indigo carmine was injected
      through the catheter. Excretion of the dye from the minor duodenal papilla was
      observed endoscopically. RESULTS: Patency of the accessory pancreatic duct was
      43% of the 291 control cases. In the 46 patients with acute pancreatitis, 8 (17%)
      had a patent accessory pancreatic duct. The difference in patency between this
      group and the normal group was significant (p < 0.01). Especially, patency of the
      accessory pancreatic duct was only 8% of the 13 patients with acute biliary
      pancreatitis. In the patients with pancreaticobiliary maljunction, biliary
      carcinoma occurred in 72% of patients with a nonpatent accessory pancreatic duct,
      but in contrast, it occurred only in 30% of those with a patent accessory
      pancreatic duct. This difference was significant (p < 0.05). Lower amylase level
      in the bile of patients with pancreaticobiliary maljunction with a patent
      accessory pancreatic duct was frequently observed than those with a nonpatent
      accessory pancreatic duct. CONCLUSIONS: A patent accessory pancreatic duct may
      prevent acute pancreatitis by lowering the pressure in the main pancreatic duct.
      In cases of pancreaticobiliary maljunction with a patent accessory pancreatic
      duct, the incidence of carcinogenesis of the bile duct might be lower, as the
      reflux of the pancreatic juice to the bile duct might be reduced by the flow of
      the pancreatic juice into the duodenum through the accessory pancreatic duct.

PMID- 14696500
TI  - Management of postoperative hemorrhage after pancreatoduodenectomy.
AB  - BACKGROUND/AIMS: Hemorrhage after pancreatoduodenectomy is a severe, life
      threatening complication. This study was conducted to determine the guidelines
      appropriate for the prevention and management of hemorrhagic complications.
      METHODOLOGY: We reviewed the medical records of 456 patients who had undergone
      pancreatoduodenectomy at our hospital between 1991 and 2000. RESULTS: Significant
      postoperative bleeding occurred in 21 patients (4.6%). Early bleeding (within the
      5th postoperative day) caused by improper intraoperative hemostasis occurred in 5
      of these cases; 3 of whom were saved by prompt operation and one by conservative
      management. The other 16 cases consisted of late bleeding (after the 5th
      postoperative day), of which 12 patients (75%) experienced pancreatic leaks and 8
      pseudoaneurysms of major arteries. "Sentinel bleeding" was evident in 8 cases.
      Angiographic embolization was performed in 8 cases, 7 of which were successful.
      Reoperation was tried in 7 cases with complete hemostasis being achieved in 2. As
      a result, 15 of 21 patients obtained complete hemostasis and the mortality rate
      from hemorrhage was 28.6% (6/21). CONCLUSIONS: Rapid decision-making is mandatory
      when bleeding stigmata such as pseudoaneurysm on CT and sentinel bleeding are
      noted. Prompt operation for early bleeding and angiographic embolization for late
      bleeding are recommended. In order to prevent hemorrhage after
      pancreatoduodenectomy, meticulously performed hemostasis and the avoidance of
      pancreatic anastomotic leaks are essential.

PMID- 14696501
TI  - Pancreatoduodenectomy for chronic pancreatitis with an inflammatory mass of
      pancreatic head: preoperative and postoperative functional assessment.
AB  - BACKGROUND/AIMS: In chronic pancreatitis patients with an inflammatory mass of
      the pancreatic head receiving pancreatoduodenectomy, postoperative quality of
      life, including nutritional status, has become important. Pre- and postoperative
      evaluation of pancreatic function is essential as an effective means of proper
      nutritional management of patients following pancreatoduodenectomy. METHODOLOGY:
      Fifteen patients with chronic pancreatitis and inflammatory mass of the
      pancreatic head who had received standard pancreatoduodenectomy were enrolled in
      this investigation. All patients had their biliary and pancreatic ducts
      reconstructed according to Child's arrangement. Furthermore, all patients had
      smooth postoperative courses and were assessed for the pancreatojejunostomy by
      magnetic resonance cholangiopancreatography at least a month after the initial
      operation. Exocrine pancreas functions were clinically assessed with various
      clinical items and two indirect pancreatic function tests: the fecal elastase
      test and the Bentiromide test. Endocrine pancreas functions were assessed using
      serum C-peptide level, HbA1 level and the need for hypoglycemic therapy. RESULTS:
      The results indicated that the pancreatojejunostomies of all patients are patent
      magnetic resonance cholangiopancreatography. All patients benefited from the
      selected symptom relief and various clinical parameters, including medications,
      dietary restrictions, body mass index and plasma albumin levels, experiencing
      pain relief and improved exocrine and endocrine functions. CONCLUSIONS:
      Pancreatic function did not deteriorate after pancreatoduodenectomy for chronic
      pancreatitis with an inflammatory mass of pancreatic head, while quality of life
      was significantly improved.

PMID- 14696502
TI  - How many millimeters do atypical epithelia of the pancreas spread intraductally
      before beginning to infiltrate?
AB  - BACKGROUND/AIMS: The pathogenesis of ordinary duct cell carcinoma of the pancreas
      is still unclear. The aim of this study was to identify which epithelial lesion
      was a precursor of duct cell carcinoma and to determine how many millimeters
      atypical epithelia spread intraductally before beginning to infiltrate.
      METHODOLOGY: Small cystic dilated lesions were studied, using 1374 autopsied
      pancreata which were mainly taken from aged patients. Serial sections were taken
      at about 5-mm intervals. Small cystic dilated lesions were defined as restricted
      dilatations of the pancreatic branch duct, which were grossly recognizable and
      therefore larger than about 1-2 mm in diameter. The degree of epithelial atypia
      of the cystic dilated lesions was histologically divided into five groups (Group
      I to V). RESULTS: Comparing PanIN to our classification, normal and squamous
      metaplasias were almost the same as Group 1. PanIN 1A and 1B almost the same as
      Group 2 (benign hyperplasia). PanIN-2 is almost the same as Group 3, and PanIN-3
      is almost the same as Group 4, which is characterized by true cribriforming, and
      a loss of nuclear polarity. Of 1374 autopsy cases, small cystic dilated lesions
      were found in 378 pancreata (27.5%). Histological examination revealed that the
      incidence of each group was 47%, 33%, 18%, 2.4% and 0.6% of 507 cystic dilated
      lesions, respectively. Dilatation of the cystic lesion and surrounding dilated
      duct resembled a precursor of IPMT in four cases, but not in another five cases.
      Group IV epithelia just infiltrated in some of the latter cases. Invasion was
      found when Group IV epithelia spread about 5-8 mm, while it rarely infiltrated
      when it spread less than 4 mm. CONCLUSIONS: The pathogenesis of ordinary duct
      cell carcinoma of the pancreas was speculated to begin with papillary growth of
      duct epithelia. Papillary atypical epithelia then begins to infiltrate when they
      spread intraductally about 5-8 mm.

PMID- 14696503
TI  - Long-term follow-up of patients with necrotizing pancreatitis treated by
      percutaneous necrosectomy.
AB  - BACKGROUND/AIMS: The objective of this follow-up study was to assess the long
      term outcome of patients with infected necrotizing pancreatitis treated with
      percutaneous catheter drainage and necrosectomy. METHODOLOGY: Nine patients
      (median age 44 years, range 19-69) with infected pancreatic necrosis and catheter
      drainage for initial treatment were evaluated after a median follow-up of 30
      months (range 15-52) with respect to quality of life (pain, diarrhea, fat
      intolerance), morphology and endocrine and exocrine pancreatic function. RESULTS:
      At follow-up all 9 patients (100%) were in good general condition with respect to
      quality of life. Only 2/9 (22%) patients had moderate to marked changes in
      computed tomography. There was mild to moderate exocrine dysfunction in 5/8 (63%)
      patients, 2/8 (25%) patients had a severe restriction of the exocrine pancreatic
      function; in one patient the serum pancreoaryl test was normal. An oral glucose
      tolerance test was performed in 6/9 patients, with a normal result in 3/6 (50%)
      patients. 2/6 (33%) patients had an impaired oral glucose tolerance test with
      metabolic pathogenesis. One patient with diabetes in the oral glucose tolerance
      test had a preexisting type II diabetes requiring insulin therapy since the onset
      of acute pancreatitis. In 3/9 (33%) patients an oral glucose tolerance test was
      not performed due to known preexisting diabetes. CONCLUSIONS: Percutaneous
      drainage of infected necrotizing pancreatitis has given good long-term results
      with regard to quality of life, endocrine and exocrine pancreatic function and
      may be an alternative to surgical treatment.

PMID- 14696504
TI  - Comparison of the functional and morphological changes in the pancreatic remnant
      between pylorus-preserving pancreatoduodenectomy and pancreatoduodenectomy.
AB  - BACKGROUND/AIMS: Pylorus-preserving pancreatoduodenectomy preserves the secretion
      of gastrointestinal hormones from the distal stomach and duodenum, whereas after
      pancreatoduodenectomy they are no longer secreted. It has been suggested that
      some gastrointestinal hormones exert a trophic effect on the pancreas, although
      this effect has not been documented in man. It was postulated that the ablation
      of gastrointestinal hormones, such as gastrin by pancreatoduodenectomy is an
      important cause of postoperative pancreatic atrophy and, since pylorus-preserving
      pancreatoduodenectomy preserves the secretion of these hormones, it would be more
      effective than pancreatoduodenectomy for the maintenance of postoperative
      pancreatic function. METHODOLOGY: We measured postoperative pancreatic function,
      parenchymal thickness of pancreas and the release of gastrin in patients who
      underwent pancreatoduodenectomy or pylorus-preserving pancreatoduodenectomy who
      had survived > 1 year without tumor recurrence. RESULTS: After pylorus-preserving
      pancreatoduodenectomy, exocrine pancreatic function, parenchymal thickness of
      pancreas and gastrin release were significantly greater than after
      pancreatoduodenectomy. CONCLUSIONS: We concluded that postoperative atrophy of
      the distal pancreas after pancreatoduodenectomy occurs, in part because of
      resections of the duodenum and distal stomach, which is the source of trophic
      stimuli, gastrin.

PMID- 14696505
TI  - A novel reconstructive procedure after pancreaticoduodenectomy: J-pouch dunking
      pancreaticojejunostomy.
AB  - Leakage of the pancreaticojejunostomy remains a major complication after
      pancreaticoduodenectomy. Several methods have been advocated in order to reduce
      anastomotic fistula but none of them reached a significant difference in
      preventing the leakage. We developed a new technique called "J-pouch dunking
      pancreaticojejunostomy". A "J" pouch is made from the distal 20 to 30 cm of
      jejunum by using a GIA linear stapler. A transverse incision is made on the
      jejunal base. As a result, we have enough jejunal stoma to anastomose the
      pancreatic remnant. A soft pancreas and small pancreatic size are known to be
      risk factors in pancreatic anastomosis. This technique is designed to eliminate
      the several factors related to pancreatic anastomotic leakage.

PMID- 14696506
TI  - Partial pancreatic head resection for pancreatic metastasis from renal cell
      carcinoma.
AB  - We report partial pancreatic head resection for pancreatic metastasis of renal
      cell carcinoma. A 71-year-old man was admitted to our hospital without any
      complaint. Contrast-enhanced computed tomographic showed a hypervascular tumor
      1.5 cm in diameter in the head of the pancreas. We performed partial head
      resection preserving the duct of Wirsung and the duct of Santorini. He is
      presently alive and well without any evidence of recurrent disease 18 months
      after the operation. Isolated pancreatic metastasis of renal cell carcinoma
      enables surgeons to perform partial pancreatic head resection in selected cases.

PMID- 14696507
TI  - A case of solid-pseudopapillary tumor of the pancreas: preoperative cyst fluid
      analysis and treatment by enucleation.
AB  - The authors report a case of a 26-year-old female who had a solid-pseudopapillary
      tumor of the pancreas. The patient had preoperative cyst fluid analysis that
      demonstrated low levels of carcinoembryonic antigen and moderate elevation in
      cyst fluid carbohydrate antigen 19-9 and lipase. Cyst fluid cytology was
      diagnostic. The tumor was successfully treated by complete enucleation.

PMID- 14696508
TI  - Spleen-preserving distal pancreatectomy with preservation of the splenic artery
      and vein for intraductal papillary-mucinous tumor (IPMT): three interesting
      cases.
AB  - Preservation of the spleen at distal pancreatectomy has recently attracted
      considerable attention. Since our first trial and success with spleen-preserving
      distal pancreatectomy with conservation of the splenic artery and vein for tumors
      of the pancreas and chronic pancreatitis, this procedure has been performed more
      frequently. Three patients with intraductal papillary-mucinous tumor underwent
      spleen-preserving distal pancreatectomy with conservation of the splenic artery
      and vein. In this procedure, the splenic vein is identified behind the pancreas
      and the connective tissue membrane is cut longitudinally above the splenic vein.
      An important point is to remove the splenic vein from the pancreas from the body
      of the pancreas toward the spleen. In one patient with intraductal papillary
      mucinous tumor in the body of the pancreas who had undergone distal gastrectomy
      for duodenal ulcer 32 years previously, residual proximal gastrectomy could be
      avoided with this procedure. In this case, the histological diagnosis was a
      pseudocyst, and epithelial dysplasia was found in other pancreatic ductuli. In
      another case, epithelia were borderline between hyperplasia and adenoma. In both
      of these cases, the histological diagnosis was different from the preoperative
      diagnosis. Even with advances in imaging techniques, diagnosis of a cystic lesion
      of the pancreas is still very difficult. Ordinary distal pancreatectomy with
      splenectomy would have been oversurgery in these two cases, which could be
      avoided using our procedure. Severe complications were not found in any of the
      three cases and the postoperative course was uneventful. The patients have been
      followed as outpatients without any recurrence. Spleen-preserving distal
      pancreatectomy with conservation of the splenic artery and vein is easy and safe,
      and should be performed for some patients with intraductal papillary mucinous
      tumor of the pancreas.

PMID- 14696509
TI  - Postoperative evaluation of function-preserving gastrectomy for early gastric
      cancer.
AB  - BACKGROUND/AIMS: We evaluated the efficacy of the following three surgical
      options in gastrectomy for early gastric cancer; 1) reduction of the extent of
      gastrectomy, 2) preservation of the vagal nerve, and 3) preservation of the
      pylorus. METHODOLOGY: The postoperative physical conditions of patients who had
      undergone 6 kinds of operating methods incorporating elements 1), 2) and 3) were
      compared. The efficacy of elements 1) and 3) was evaluated by comparison among a
      2/3 proximal gastrectomy group (2/3-PG group, n = 5), 4/5 proximal gastrectomy
      group (4/5-PG group, n = 7), and total gastrectomy group (TG group, n = 12). The
      efficacy of elements 1), 2) and 3) was also evaluated by comparison among a
      pylorus-preserving gastrectomy (PPG) group with preservation of the vagal nerve
      (PPGV group, n = 15), 2/3 distal gastrectomy group with preservation of the vagal
      nerve (2/3-DGV group, n = 12), and 4/5 distal gastrectomy group without
      preservation of the vagal nerve (4/5-DG group, n = 15). RESULTS: Body weight loss
      and the incidence of abdominal symptoms and anemia in the 2/3-PG group, PPGV or
      2/3-DGV group were less frequent than in the TG group or 4/5-DG group. The
      increases in acetaminophen concentration in the 2/3-PG group, PPGV or 2/3-DGV
      groups, and the changes in blood sugar and insulin levels in the 2/3-PG or PPGV
      group were modest, while hypergastrinemia in the 2/3-PG group was remarkable. The
      insulinogenic index was high in the 2/3-DGV group, and the plasma cholecystokinin
      changes and contraction pattern of the gallbladder resembled their preoperative
      pattern in the PPGV and 2/3-DGV groups. These results indicated that the patients
      in the 2/3-PG group owed their benefits to elements 1) and 3), the 2/3-DGV group
      to elements 1) and 2), and the PPGV group to elements 1), 2) and 3). CONCLUSIONS:
      Three surgical options in gastrectomy procedures for early gastric cancer, 1)
      reduction of the extent of gastrectomy, 2) preservation of the vagal nerve, and
      3) preservation of the pylorus, were individually confirmed to have benefits for
      better postoperative quality of life.

PMID- 14696510
TI  - The benefit of laparoscopy-assisted distal gastrectomy compared with conventional
      open distal gastrectomy: a case-matched control study.
AB  - BACKGROUND/AIMS: Laparoscopy-assisted distal gastrectomy is a surgical procedure
      which is safe, useful, and technically feasible for patients with early gastric
      cancer. The aim of this study is to determine whether laparoscopy-assisted distal
      gastrectomy is also superior to conventional open distal gastrectomy.
      METHODOLOGY: The study comprised 27 consecutive patients with early gastric
      cancer who were admitted to our hospital from 1997 to 2000 and underwent distal
      gastrectomy. Ten patients underwent laparoscopy-assisted distal gastrectomy; and
      17 conventional open distal gastrectomy. RESULTS: Estimated blood loss was 17.7
      +/- 12.1 g during laparoscopy-assisted distal gastrectomy, and 250.0 +/- 160.8 g
      during conventional open distal gastrectomy. The difference was statistically
      significant (p < 0.001). The day of ambulation (2.7 +/- 0.7 vs. 1.0 +/- 0.0), and
      start of liquid diet (6.9 +/- 1.2 vs. 4.3 +/- 0.5) were significantly delayed in
      conventional open distal gastrectomy compared with laparoscopy-assisted distal
      gastrectomy (p < 0.001, p < 0.05). At the 3rd postoperative day, the serum C
      reactive protein level in laparoscopy-assisted distal gastrectomy decreased
      significantly more than that in conventional open distal gastrectomy (4.2 +/- 1.7
      vs. 9.4 +/- 2.5: p < 0.05). No postoperative complication was found in
      laparaoscopy-assisted distal gastrectomy. CONCLUSIONS: Laparoscopy-assisted
      distal gastrectomy is a safe and useful operation for most early gastric cancers.
      Laparoscopy-assisted distal gastrectomy has been superior to conventional open
      distal gastrectomy.

PMID- 14696511
TI  - Helicobacter pylori infection in hemodialysis patients.
AB  - BACKGROUND/AIMS: Studies on the relationship between high serum urea nitrogen,
      creatinine and Helicobacter pylori infection in hemodialysis patients still give
      conflicting results. In the present study we investigated the prevalence of
      Helicobacter pylori positivity in patients with hemodialysis [HD(+)] and without
      hemodialysis [HD(-)] and assessed the relationship between clinical factors,
      serum urea nitrogen, creatinine levels and Helicobacter pylori prevalence in
      these patients. METHODOLOGY: 117 patients with dyspeptic complaints were included
      in the study. They consisted of 36 HD(+) patients (31%) and 81 HD(-) patients
      (69%). Endoscopy was performed and gastric antral biopsies were obtained for
      immunohistochemical analysis for Helicobacter pylori in all patients. RESULTS:
      Helicobacter pylori was positive in 53(45%) of 117 patients [Hp(+)]. In
      univariate analysis Hp(+) patients received hemodialysis therapy significantly
      less often (P = 0.002) and had lower serum urea nitrogen (P = 0.0008) and
      creatinine (P = 0.003) levels than Hp(-) patients. There was no significant
      difference in age, gender, endoscopic findings or comorbid conditions
      (hypertension or diabetes mellitus) between these groups. Multivariate logistic
      regression analysis revealed that only the serum urea nitrogen level was
      significantly associated with Helicobacter pylori prevalence (P = 0.008).
      CONCLUSIONS: These results indicate that high serum urea nitrogen seems to
      correlate with a low prevalence of Helicobacter pylori infection and hemodialysis
      patients with high serum urea nitrogen may be protected against Helicobacter
      pylori infection.

PMID- 14696512
TI  - A combination immunochemotherapy of 5-fluorouracil, cisplatin, leucovorin, and OK
      432 for advanced and recurrent gastric carcinoma.
AB  - BACKGROUND/AIMS: Based on theories of biochemical modulation and immunotherapy, a
      novel regimen consisting of 5-fluorouracil, cisplatin, leucovorin, and OK-432
      (FLPO therapy) was devised for the treatment of patients with advanced and
      recurrent gastric carcinoma. METHODOLOGY: The 14-day combination therapy
      consisted of continuous infusion of 5-fluorouracil (250 mg/m2/day), a bolus
      injection of 10 mg cisplatin and 30 mg leucovorin every other day, and a
      subcutaneous injection or per oral administration of OK-432 (3KE or 5KE) every
      other day. Thirty patients completed 59 courses of treatment consisting of 2
      weeks of therapy followed by at least 2 weeks rest. RESULTS: The overall response
      rate was 40%, with 1 complete response and 11 partial responses observed. All
      twelve patients responded after 1 course of treatment. The response rate differed
      depending upon tumor location, 22.2% at the primary site, 60.0% in the lymph
      nodes, 45.5% with peritoneal dissemination, 44.4% with liver metastases, 50.0% in
      the lung, and 100.0% with skin metastases. The most frequently observed toxicity
      was stomatitis (53.3%). The overall incidence of toxicities of grade 3 or greater
      was 6.6%, including diarrhea (3.3%) and stomatitis (3.3%). One patient required
      treatment interruption because of the grade 3 toxicity of diarrhea. The median
      survival time was 198 days overall, 242 days for responders and 125 days for non
      responders. CONCLUSIONS: FLPO therapy seemed to be an effective regimen for the
      treatment of advanced and recurrent gastric carcinoma.

PMID- 14696513
TI  - Endoscopic findings in a biennial follow-up program in patients with pernicious
      anemia.
AB  - BACKGROUND/AIMS: It is known that patients with pernicious anemia have a higher
      risk of gastric neoplasms. However, the optimal endoscopic follow-up in these
      patients has not been properly defined. This study was aimed to assess the
      usefulness of an endoscopic follow-up program. METHODOLOGY: We analyzed the
      endoscopic and histological findings of the first endoscopy performed in a group
      of 128 patients with the diagnosis of pernicious anemia who were referred to the
      Endoscopic Unit, and we evaluated the results of the biannual follow-up
      endoscopies made to 68 of them. RESULTS: The initial endoscopy did not provide
      evidence of any lesions in 107 patients (83.5%), and polypoid lesions were found
      in 12 cases (9.4%). The histological results showed gastric dysplasia in 3
      patients (2.3%) and carcinoid tumor in 2 cases (1.6%). No cases of gastric
      carcinoma were found. During the endoscopic follow-up of 68 patients, in 52 of
      them (76.8%) there were no endoscopic findings, and raised lesions were detected
      in 8 patients (11.8%). Three cases of gastric dysplasia were found. No cases of
      gastric carcinoma or carcinoid were detected during the follow-up. CONCLUSIONS:
      We suggest that a biannual endoscopic follow-up in not useful for the early
      detection of gastric neoplasms in patients with pernicious anemia.

PMID- 14696514
TI  - How to eradicate Helicobacter pylori using amoxicillin and omeprazole in the
      remnant stomach.
AB  - BACKGROUND/AIMS: We previously investigated the effects of amoxicillin/omeprazole
      combined therapy on patients who were Helicobacter pylori (H. pylori) positive
      after gastrectomy for the treatment of gastric cancer, and we determined the
      difference in amoxicillin dosage between the therapeutic successes and failures.
      In the present study, assuming that amoxicillin dosage should be determined on
      the basis of body weight of each patient, we examined whether the eradication of
      H. pylori would be improved by using this novel dose-selection method.
      METHODOLOGY: We have previously reported about eradication of H. pylori of
      remnant stomach as follows. Patients who underwent gastrectomy for the treatment
      of gastric cancer were enrolled if H. pylori was detected in their remnant
      stomach after the operation. Of these patients, 22 were treated with amoxicillin
      at 750 mg/day for 2 weeks and omeprazole at 20 mg/day for 8 weeks. For the
      evaluation of H. pylori eradication, endoscopic examination and 13C-urea breath
      test were performed 12 weeks after the initiation of the treatment. The
      amoxicillin dosage in the therapeutic successes was compared with that in the
      therapeutic failures, and we found that the dosage was 14.1 +/- 1.5 and 12.5 +/-
      1.5 mg/kg/day in the successes and the failures, respectively. Following these
      results, another 10 H. pylori-positive patients were treated with amoxicillin
      greater than 16 mg/kg/day for 2 weeks and omeprazole at 20 mg/day for 8 weeks,
      and H. pylori eradication was evaluated as mentioned above. The efficacy of the
      drug therapy on H. pylori infection was compared between the two groups that one
      group (Group A) is treated with amoxicillin 750 mg/day for 2 weeks and omeprazole
      at 20 mg/day for 8 weeks and the other group (Group B) is treated with 1250
      mg/day for 2 weeks and omeprazole at 20 mg/day for 8 weeks. RESULTS: The
      eradication rate of H. pylori in Group B (84.6%) was higher than that in Group A
      (42.1%). There was significant difference between the two groups (p = 0.028).
      CONCLUSIONS: We assumed that the optimal dosage of amoxicillin was over 15.6
      mg/kg/day for omeprazole-amoxicillin combined therapy for gastrectomized patients
      who were H. pylori positive, and the favorable therapeutic effects could be
      obtained by applying this amoxicillin dosage to the eradication of H. pylori.

PMID- 14696515
TI  - Increased risk of rebleeding of peptic ulcer bleeding in patients with comorbid
      illness receiving omeprazole infusion.
AB  - BACKGROUND/AIMS: The study aimed to evaluate whether administration of
      intravenous omeprazole has different rebleeding rates for peptic ulcer bleeding
      of patients with and without comorbid illness. METHODOLOGY: A total of 80
      patients with peptic ulcer bleeding were enrolled after therapeutic endoscopy to
      achieve hemostasis. Each patient had received omeprazole 80 mg bolus loading and
      40 mg twice daily for three days (total dosage of 320 mg within 3 days). Two
      subgroups were divided, based on the absence (Group A) or presence (Group B) of
      one or more comorbid illnesses, such as chronic obstructive pulmonary disease,
      congestive heart failure, uremia, cirrhosis, diabetes mellitus, and old stroke.
      The 7-day and 28-day rebleeding rates were recorded. RESULTS: The presence of
      comorbid illness had a higher rebleeding rate than those without comorbid illness
      (7-day: 32.5 vs. 2.5%, p < 0.05; 28-day: 37.5 vs. 5.0%, p < 0.05). Patients with
      two or more comorbid diseases had an even higher risk of rebleeding than those
      with a single comorbid illness (66.7% vs. 26.5%, p < 0.05). CONCLUSIONS: Low-dose
      infusion of omeprazole can achieve favorable control of rebleeding in the
      patients with peptic ulcer bleeding but without comorbid diseases. As patients
      with comorbid illness had a higher risk of rebleeding, a higher dosage or
      prolonged duration of omeprazole infusion would be rationally indicated to
      prevent risk of rebleeding.

PMID- 14696517
TI  - Gasless laparoscopy-assisted distal gastrectomy for early cancer via mini
      laparotomy using an abdominal wall lift.
AB  - BACKGROUND/AIMS: To investigate the technical ease and results of gasless
      laparoscopy-assisted distal gastrectomy with lymph node dissection via mini
      laparotomy using abdominal wall lift for early gastric cancer. METHODOLOGY: We
      submitted 20 patients to laparoscopy-assisted distal gastrectomy for early
      gastric cancer located in the middle or lower stomach. The initial 10 cases
      underwent perigastric lymph node dissection (D1), and the subsequent 10 cases
      received further dissection around the left gastric and common hepatic arteries
      (D1 + a). Mini-laparotomy was placed at the beginning of the procedure. We lifted
      up the laparotomy and the subcutaneous tissue around the umbilicus by retractors.
      We accomplished the dissection, resection and reconstruction mainly via the mini
      laparotomy using a direct view and a laparoscopic image. RESULTS: Two cases were
      converted to open. The operative time was significantly longer in D1 + a (225 +/-
      49 min) than in D1 (172 +/- 38 min). Blood loss was significantly more in D1 + a
      (247 +/- 155 mL) than in D1 (109 +/- 60 mL). There was no difference between the
      two groups in terms of days to first flatus, first oral intake or discharge from
      the hospital. Postoperative complications included 2 wound infections each in D1
      and D1 + a group, and 1 anastomotic stenosis in D1 + a group. CONCLUSIONS:
      Gasless laparoscopy-assisted distal gastrectomy with D1 + a via mini-laparotomy
      using abdominal wall lift seems to be feasible and useful for early gastric
      cancer.

PMID- 14696516
TI  - High-dose rabeprazole/amoxicillin therapy as the second-line regimen after
      failure to eradicate H. pylori by triple therapy with the usual doses of a proton
      pump inhibitor, clarithromycin and amoxicillin.
AB  - BACKGROUND/AIMS: Some patients are refractory to the usual triple therapy for
      eradication of Helicobacter pylori, consisting of a proton pump inhibitor,
      amoxicillin and clarithromycin, so there needs to be an alternative strategy for
      retreatment after failure to eradicate the infection. METHODOLOGY: The study
      group comprised 17 H. pylori-positive patients who had failed to clear H. pylori
      infection after 1 week of treatment with usual doses of proton pump inhibitor,
      amoxicillin and clarithromycin. The sensitivity of H. pylori to clarithromycin
      and amoxicillin, and the CYP2C19 genotype status of each patient were determined
      and treatment with rabeprazole (10 mg qid) and amoxicillin (500 mg qid) for 2
      weeks was started. RESULTS: Eleven patients were infected with a clarithromycin
      resistant strain of H. pylori. Twelve patients had the homozygous extensive
      metabolizer genotype, 5 had the heterozygous extensive metabolizer genotype and
      there were none with the poor metabolizer genotype of CYP2C19. All patients were
      successfully cleared of their H. pylori infection without any adverse effects,
      irrespective of CYP2C19 genotype status (100%, 95% confidence interval: 76-100%).
      CONCLUSIONS: High-dose dual therapy with rabeprazole (10 mg qid) and amoxicillin
      (500 mg qid) for 2 weeks appears useful treatment strategy after failure of
      eradication of H. pylori by the usual triple proton pump
      inhibitor/amoxicillin/clarithromycin therapy.

PMID- 14696519
TI  - Kinetics of antibiotics release from ceramic implants.
AB  - Presented study describes kinetics of antibiotics release: cefazolin, gentamicin,
      netilmicin and vancomycin, from two types of ceramic implants: corundum and
      apatite cement prepared for osteosurgery. The experiments was based on our
      experimental model developed previously, in which the extraction of antibiotics
      from implants to polyurethane sponge was made for 3 days. The concentrations of
      antibiotics in the sponges were determined by spectrophotometric and biological
      methods. Among all ceramic materials tested, corundum implants with netilmicin
      and cement implants with gentamicin proved to be most efficacious regarding
      antibiotics release within 3 days of extraction to polyurethane sponge (yield of
      the release was 50% and 80% respectively). The lowest release was obtained in the
      case of cefazolin from cement disks (yield about 0.02%). The kinetics and
      effectiveness of antibiotics release from the ceramic implants tested depended on
      ceramic carrier and kind of the drug.

PMID- 14696518
TI  - Long-term survival after treatment of gastric carcinoma with liver metastases. A
      case report.
AB  - A 58-year-old fish dealer presented with epigastric pain. Radiographic and
      endoscopic studies showed a Borrmann type I gastric carcinoma on the anterior
      surface of the body of the stomach near the greater curvature, and a metastatic
      work-up demonstrated two masses in the right lobe of the liver (segment 6 and 8).
      The preoperative diagnosis was gastric carcinoma with liver metastasis (stage
      IV). At laparotomy no tumors were found in the left lobe of the liver or the
      peritoneum, and subtotal gastrectomy, D2 lymph node dissection, and segment 6 and
      8 partial resection was performed. Ligation of the right portal vein and
      intraoperative common hepatic artery chemotherapy (one shot) was performed to
      destroy any non-visible metastatic tumors in the right lobe of the liver.
      Histologically, both the gastric and the hepatic lesions were adenocarcinoma. An
      aneurysm of the common hepatic artery developed after another shot of
      chemotherapy through the celiac artery one month after the operation. The
      aneurysm ruptured, and a small fistula formed between the aneurysm and the
      duodenum. The aneurysm was successfully treated by aneurysmectomy, and the
      perforated duodenal wall was managed by catheter duodenostomy. The patient is
      alive and pursuing his previous occupation with no evidence of tumor recurrence.
      He has been attending the outpatient clinic for follow-up every 6 months for 17
      years since the operation. Removal of the primary and metastatic lesions with
      portal vein ligation and intra-arterial chemotherapy is therefore effective as an
      active measure to prolong the survival time of gastric carcinoma patients with
      metastases limited to a single lobe of the liver.

PMID- 14696520
TI  - [Investigation of biocompatibility of the apatite cement].
AB  - The results of experimental studies of biocompatibility of the apatite cement,
      implanted in the muscular tissue of rats and bone tissue of rabbits were
      presented in this study. Investigations of the local reactions of the muscular
      tissue were carried out on 18 rats of Wistar type by implanting samples from the
      apatite cement in the dorsal muscles. Macroscopic and microscopic investigations
      were carried out 7, 14, 30, 180, 270 days after the implantation. Investigations
      of local reactions of bone tissue were carried out on 12 rabbits of New Zealand
      breed. By implanting the tested material into the femoral bone in the region of
      trochanter. Sections of the animals were made 1, 3, 6, and 9 months after the
      surgery. In the early period active inflammatory process was seen in the muscles
      in the direct vicinity of the implant and then it disappeared leading to
      formation of a thin fibrous connective tissue capsule. Histological
      investigations made of bone tissue later showed, formation of young tissue with
      small focuses of fibrous connective tissue. In the carried out investigations it
      was shown that the apatite cement is characterized with a high degree of
      biocompatibility and osteoinductive activity.

PMID- 14696521
TI  - [Investigation of tissue reaction of apatite cement implants impregnated with
      vancomycin].
AB  - Investigation of biocompatibility degree of apatite cement as a carrier of
      antibiotic--vancomycin was the purpose of the experimental study. Investigation
      of local reactions of muscular tissue was carried out on 18 rats of Wistar type,
      by implanting samples of apatite cement with vancomycin in the dorsal muscles.
      Sections of the animals and microscopic investigations were made 7, 14, 30, 90,
      180 and 270 days after the implantation. Investigation of local reactions of bone
      tissue were carried out on 12 rabbits of New Zealand breed, by implanting the
      investigated samples into the femoral bone in the region of trochanter.
      Macroscopic, radiological and microscopic investigations were carried out 1, 3, 6
      and 9 months after the surgery. The obtained results of the investigations from
      muscular and bone tissue, were compared to the investigations in analogical
      tissues of apatite cement without the medication. In macro- and microscopic
      investigations in the early period inflammatory reaction of muscles was noticed
      to be stronger around the samples with vancomycin, in comparison to the control
      implant. In the later period there was no inflammatory reaction and a thin
      fibrous connective tissue surrounded the implant and a histological picture was
      similar, as in cases of an implant without the antibiotic. The local reaction of
      bone tissue both in the control and in the investigated group (apatite cement
      with vancomycin) was similar. In the early period the proliferation of rich
      cellular connective tissue, was noticed. In the later period starting from the
      3rd month, formation of young bone tissue was noticed and only locally there were
      focuses of fibrous tissue. The process observed after splitting of the tested
      materials into bone tissue, was very similar to healing processes after long bone
      fraction. The carried out investigations showed, that tissue reaction after
      implantation of apatite cement and its composite with vancomycin, was very
      similar and showed a high degree of tissue biocompatibility.

PMID- 14696522
TI  - Intraoperative hemostasis during kidney transplantation and the use collagen mesh
      dressing covered by fibrin glue (TachoComb).
AB  - In this paper we present influence of use of haemostatic dressing TachoComb, onto
      bleeding from surface of transplanted kidney. Kidney transplantation (KTX) seems
      to be main method of treatment of terminal renal failure. Enlarging number of KTX
      results in growing frequency of intra and postoperative complications.
      Hemorrhagic complications can impact clinical status of recipient and graft
      function. Haemostatic dressing was applied at 29 cases. Control group in which
      only gas compresses were used consisted of 25 patients. It was proved, that use
      of dressing from collagen mesh covered by fibrin glue TachoComb, after kidney
      transplantation diminished parenchymal bleeding and time necessary to get
      complete hemostasis.

PMID- 14696523
TI  - The modification of renal transplantation with the usage of own polyethylene
      receptacle.
AB  - In this study a method of elimination of the second warm ischemia is shown. The
      method is based on the application of a specially constructed polyethylene bag,
      in which the transplanted kidney is placed in the time course from a removal from
      ice to the reconstruction of vessel flow. The bag is built of polyethylene foil
      HDPE of low density produced under high pressure. Own construction of the bag
      (three spaces and polyethylene) enables the storage of a transplanted organ at
      the stable temperature +4 Celsius degrees. Thanks to the separation of containers
      for melting ice and for the kidney, possible becomes unrestrained performance of
      both venous and arterial anastomosis independently of existing operative
      conditions. Due to the applied method of the elimination of the second warm
      ischemia with the usage of own construction of polyethylene bag HDPE, one can
      expect better early renal function after transplantation--decrease in the number
      of cases and shortening of the time of acute tubular necrosis (ATN--Acute Tubular
      Necrosis).

PMID- 14696524
TI  - Effects of concentration boundary layers in a transport of electrolyte solutions
      through horizontal mounted polymeric membrane.
AB  - The results of experiment of diffusive transmembrane transport in a single
      membrane osmotic-diffusive electrochemical cell were presented. In all
      experiments one of the vessels was filed with pure water, and the second one-
      with aqueous potassium chloride solution in aqueous ammonia solutions of constant
      concentration. The flux of potassium chloride was assigned according to the
      following measure procedure. In a first step we assigned the time dependence of
      potassium chloride flux in conditions of uniform mechanically stirred solution
      with speed of 500 rpm. In a second step those characteristics were assigned in
      conditions of mechanically unstirred solution. Each experiment was made for two
      configurations of gravitational membrane system: (i) with the water in a vessel
      above the membrane and solution below it (configuration A) (ii) with the solution
      in a vessel above the membrane and water below it (configuration B). Taking under
      the consideration the values of potassium chloride flux in steady state for
      different solution concentration of the same substances and the same
      configurations of membrane system, the dependencies of potassium chloride flux
      from the solution concentration differences were made appropriately. On the base
      of those experiments the solute flux concentration boundary layers effects
      (jCBLE) were counted. Moreover it was shown that single-membrane osmotic
      diffusive electrochemical cell has rectifier and amplifying of diffusive flow
      features. The coefficients, appropriately, of asymmetry and amplification of
      diffusive flux are the measurements of those features.

PMID- 14696525
TI  - [In vitro study of polymer coatings on electronic elements].
AB  - The paper presents the results of investigations of polymer coatings used as
      capsules for implantable microelectronic devices for medical applications. Such
      devices work in artificial pacemakers and as feeding systems, in nerve ending
      stimulator sets. Biocompatible and biostable polysulfone capsules for integrated
      circuits and batteries have been prepared. Preliminary investigation of overall
      chemical stability of encapsulated electronic devices in Ringer's solutions, has
      been carried out as a function of immersion time. Influence of number of coating
      polysulfone layers on voltage-stability of batteries immersed in 0.9% NaCl
      solution has been measured with time. A comparative study of silicone (SIL)
      coating and double coating with silicone and polysulfone (SIL + PSU) in an in
      vitro test has been carried out.

PMID- 14696526
TI  - 'Pay for performance' brings new luster to capitation.

PMID- 14696527
TI  - Groups take steps to improve data collection, clinical scores.

PMID- 14696528
TI  - Tool allows capped groups to forecast resource consumption.

PMID- 14696529
TI  - New HEDIS data show system still falls short on 'best practice'.

PMID- 14696530
TI  - Top DRGs still drive hospital costs, LOS.

PMID- 14696531
TI  - Top hospitals show that quality, efficiency not always costly.

PMID- 14696532
TI  - Improved risk stratification boosts yield of DM, CM programs.

PMID- 14696533
TI  - Initiative gives a boost to e-health development and research.
AB  - Perhaps not, according to experts involved with a new e-health initiative aimed
      at beefing-up the research base for e-health development. Sponsors are aiming to
      go a long way towards bridging that gap, and they plan to produce--in a very
      short period of time--an array of tools that health care organizations can make
      use of right away, particularly with respect to chronic DM. Learn more about what
      researchers are tackling in this initiative and how it might help your
      organization's e-health plans.

PMID- 14696534
TI  - Epidemic of obesity fuels demand among payers for alternatives to bariatric
      surgery.
AB  - Why? Because they're finding that obesity is a significant factor involved with
      many costly chronic diseases, and financial decision-makers are concluding that
      bariatric surgery--while successful in many cases--is simply too expensive and
      too risky to cover for the large numbers of individuals who are morbidly obese.
      See how one EAP is attempting to meet this challenge by designing a program that
      incorporates the psychological and medical components of weight management.

PMID- 14696535
TI  - Health plan invests in prevention to boost outcomes in cardiac care.

PMID- 14696536
TI  - Multicampus outbreak of HIV in North Carolina spurs quick state action.
      Prevention, testing program targets black colleges.
AB  - Thanks to a statewide HIV RNA testing program, North Carolina public health
      officials learned earlier this year that there was a new outbreak of HIV
      infection among students at more than 10 colleges across the state. An
      investigation already has found links between many of the students, and the
      discovery has given rise to a stronger, statewide push for prevention, testing,
      and counseling programs at 12 minority colleges.

PMID- 14696537
TI  - State works with colleges on testing and prevention. State officials say more
      funding is needed.
AB  - An outbreak of HIV among college students has made the public health challenge
      clear: either make effective prevention, testing, and counseling services
      available to at-risk youths, or expect in a few years to add more young people to
      the state's waiting list for HIV medications.

PMID- 14696538
TI  - How a Nashville church became prevention leader. Faith ministry reaches out to
      MSM, prostitutes.
AB  - Twenty years after a founding member of the Metropolitan Interdenominational
      Church of Nashville, TN, died from AIDS, the church has paved new ground in
      showing what a faith-based institution can do to educate the public about
      HIV/AIDS and provide compassionate care to people who are infected.

PMID- 14696539
TI  - Special coverage of 41st IDSA conference. Study: Syphilitic hepatitis connected
      to liver disease. Diagnosis is uncommon, but does occur.
AB  - Investigators in Washington, DC, have discovered cases of HIV patients who have
      significant liver dysfunction that is caused by secondary syphilis instead of the
      usual suspects--hepatitis C, medication side effects, and substance abuse.

PMID- 14696541
TI  - AIDSinfo starts new Live Help web service.

PMID- 14696540
TI  - Special coverage of 41st IDSA conference. Primary care doctors fail to offer
      tests, survey says. Medical students need additional training.
AB  - A new survey shows that most family practitioners often fail to offer HIV testing
      to their sexually active patients, and many even neglect to offer the test to
      pregnant patients. But testing and counseling should be a routine part of
      physicals and physician-patient care, according to the CDC.

PMID- 14696542
TI  - FDA notifications. Gilead issues letter about virologic failure.

PMID- 14696543
TI  - Church becomes leader in mobilizing others.
AB  - When a Nashville, TN, church spreads the word about HIV/AIDS education, the
      repercussions can be felt hundreds of miles away. The Metropolitan
      Interdenominational Church mobilizes churches in Tennessee, Alabama, and
      elsewhere to offer their congregations and communities education, information,
      and understanding about HIV and AIDS.

PMID- 14696544
TI  - Web site promotes gay HIV-risk awareness.

PMID- 14696545
TI  - State department hit with second HIV discrimination suit.

PMID- 14696547
TI  - $5 million jury award overturned in HIV discrimination case.

PMID- 14696546
TI  - Protests launched against Cirque du Soleil for HIV bias.

PMID- 14696548
TI  - Gross negligence claim fails in failure to test blood claim.

PMID- 14696549
TI  - State department responds to HIV discrimination suit.

PMID- 14696550
TI  - New AIDS initiative responds to looming crisis in Asia.

PMID- 14696552
TI  - Auto sales company cleared of HIV discrimination.

PMID- 14696551
TI  - Intervention could halt India's rise to the top of new HIV cases.

PMID- 14696553
TI  - HIV-positive status could change prisoner's sentence.

PMID- 14696554
TI  - Insurance coverage. Penalty for failing to provide insurance upheld on appeal.

PMID- 14696555
TI  - Criminal exposure. Rare procedural tool denied man convicted of HIV exposure.

PMID- 14696556
TI  - Court order for juvenile offender's AIDS testing overturned.

PMID- 14696557
TI  - Disability benefits. Court orders review for HIV-positive man who lost benefits.

PMID- 14696558
TI  - Prisons. Failure to follow procedures bars inmate's HIV-exposure claim.

PMID- 14696559
TI  - AACTG A5095, Trizivir, and the role of all-nucleoside regimens: an editorial.

PMID- 14696560
TI  - Abandon Trizivir when it's working well? A rebuttal.

PMID- 14696561
TI  - Atazanavir: clinical use.

PMID- 14696562
TI  - Drug profile: atazanavir (Reyataz, ATV).

PMID- 14696563
TI  - HIV and solid organ transplantation.

PMID- 14696564
TI  - Treatment of chronic hepatitis B in the HIV-infected patient.

PMID- 14696565
TI  - The cure: we get what we demand.

PMID- 14696566
TI  - Enfuvirtide (Fuzeon).
AB  - The FDA approved enfuvirtide (Fuzeon) in spring 2003 to use with other anti-HIV
      drugs in children age six and older and in adults who have used anti-HIV therapy
      before. Enfuvirtide is in a new class of drugs called entry inhibitors. The drug
      works at the start of HIV's reproduction cycle by blocking its ability to infect
      an immune cell. This occurs at the point when HIV fuses to the cell's outer wall
      in order to gain entry into it.

PMID- 14696567
TI  - FTC (emtricitabine, Emtriva).
AB  - The FDA approved FTC (emtricitabine, Emtriva) in July 2003 for use by adults in
      combination with other anti-HIV drugs. FTC is a nucleoside analog reverse
      transcriptase inhibitor (NRTI). Other drugs in this class include 3TC, abacavir,
      AZT, Combivir, d4T, d4T XR, ddC, ddI, ddI EC and Trizivir.

PMID- 14696568
TI  - Atazanavir (Reyataz).
AB  - Atazanavir (Reyataz) is a protease inhibitor that received FDA approval in June
      2003. Other approved drugs in this class include amprenavir, indinavir, Kaletra
      (ritonavir + lopinavir), nelfinavir, ritonavir and saquinavir.

PMID- 14696569
TI  - Facial and limb fat loss: lipoatrophy.
AB  - Since the advent of potent anti-HIV therapy there have been increasing reports of
      changes in body composition among people living with HIV. These include increases
      in fat in various areas of the body (the stomach area, behind the base of the
      neck and/or breast enlargement) or decreases in body fat (in the face, arms,
      and/or legs) and changes in the way the body processes fats (called lipids). Any
      combination of these conditions is called lipodystrophy. While all these
      conditions have been lumped together, it's likely they are actually different
      syndromes which are caused by different things.

PMID- 14696570
TI  - Interfering with RNA: kill the messenger.
AB  - A number of scientific papers were published in 2002 describing the discovery of
      a process called RNA interference, or RNAi. The newly discovered process, whereby
      small strands of RNA can block the development of new genetic material, was
      called the "breakthrough of the year" in 2002 by Science magazine. RNAi has
      excited AIDS researchers because it has both short- and long-term potential for
      significantly improving the treatment of HIV disease.

PMID- 14696571
TI  - Interleukin-2: SILCAAT study to continue.
AB  - In late 2002, Chiron Corporation announced its decision to shut down a large
      pivotal study of the drug, interleukin-2 (IL-2, Proleukin). In the days and weeks
      following the announcement, researchers and community activists met with the
      company to negotiate for the SILCAAT study to continue. In February 2003, heroic
      efforts by non-Chiron scientists to continue this important study were
      successful, and a transition to the study from Chiron into independent hands was
      completed. The study will continue.

PMID- 14696572
TI  - Sex, gender and HIV.
AB  - There is an ongoing dialogue within HIV research about how HIV affects men and
      women differently and how they may respond to therapy differently. What is often
      overlooked is the difference between sex and gender. Sex is based in a person's
      biology. Gender is based in how society treats men and women because of their sex
      and how their roles and responsibilities are generally ascribed to them. Sex and
      gender may play a role in the differences seen between men and women living with
      HIV. So what are those differences and how do they impact the course of HIV in
      men and women? This article will attempt to answer some of those questions.

PMID- 14696573
TI  - Putting off for tomorrow...

PMID- 14696574
TI  - Sublime versus simple side effect stories (or, forget the adiponectin, just stop
      smoking). 5th International Workshop on Adverse Drug Reactions and Lipodystrophy
      in HIV. July 8-11, 2003, Paris.

PMID- 14696575
TI  - Surviving AIDS, and beyond. Interview by Dr. Deborah J. Cotton.

PMID- 14696576
TI  - HCV-coinfection is associated with diabetes and CD4 decline.
AB  - In February 2001, Dr. Robert Zackin became the first HIV-infected individual to
      receive a heart transplant. A biostatistician whose research focus is HIV, Dr.
      Zackin was the senior author of the paper published in the New England Journal of
      Medicine summarizing his case and providing 2-year follow-up from his successful
      transplant (N Engl J Med 2003;348:2323-8). Recently, Dr. Deborah J Cotton spoke
      with Dr. Zackin about life as both patient and researcher, the controversies
      surrounding solid-organ transplantation in HIV-infected individuals, and
      surviving AIDS and advanced cardiomyopathy.

PMID- 14696577
TI  - Larry Lehman receives John Kappers AIDS Community Service Award.

PMID- 14696578
TI  - "Hereby devised and bequeathed".

PMID- 14696579
TI  - Three new drugs approved by FDA.

PMID- 14696580
TI  - True or false: the HIV knowledge test.

PMID- 14696581
TI  - [The reorganization of dialysis in process. Interview by Bernadette Fabregas].

PMID- 14696582
TI  - [Dilated cardiomyopathy].

PMID- 14696583
TI  - [Ulcerative colitis].

PMID- 14696584
TI  - Analysis of recent papers in hypertension. Post menopausal hormone replacement
      therapy prevents diabetes.

PMID- 14696585
TI  - Microgravity and space processes.

PMID- 14696586
TI  - Life sciences.

PMID- 14696587
TI  - Space colonization.

PMID- 14696588
TI  - Materials trade study for lunar/gateway missions.
AB  - The National Aeronautics and Space Administration (NASA) administrator has
      identified protection from radiation hazards as one of the two biggest problems
      of the agency with respect to human deep space missions. The intensity and
      strength of cosmic radiation in deep space makes this a 'must solve' problem for
      space missions. The Moon and two Earth-Moon Lagrange points near Moon are being
      proposed as hubs for deep space missions. The focus of this study is to identify
      approaches to protecting astronauts and habitats from adverse effects from space
      radiation both for single missions and multiple missions for career astronauts to
      these destinations. As the great cost of added radiation shielding is a potential
      limiting factor in deep space missions, reduction of mass, without compromising
      safety, is of paramount importance. The choice of material and selection of the
      crew profile play major roles in design and mission operations. Material trade
      studies in shield design over multi-segmented missions involving multiple work
      and living areas in the transport and duty phase of space mission's to two Earth
      Moon co-linear Lagrange points (L1) between Earth and the Moon and (L2) on back
      side of the moon as seen from Earth, and to the Moon have been studied. It is
      found that, for single missions, current state-of-the-art knowledge of material
      provides adequate shielding. On the other hand, the choice of shield material is
      absolutely critical for career astronauts and revolutionary materials need to be
      developed for these missions. This study also provides a guide to the
      effectiveness of multifunctional materials in preparation for more detailed
      geometry studies in progress.

PMID- 14696589
TI  - HUMEX, a study on the survivability and adaptation of humans to long-duration
      exploratory missions, part I: lunar missions.
AB  - The European Space Agency has recently initiated a study of the human responses,
      limits and needs with regard to the stress environments of interplanetary and
      planetary missions. Emphasis has been laid on human health and performance care
      as well as advanced life support developments including bioregenerative life
      support systems and environmental monitoring. The overall study goals were as
      follows: (i) to define reference scenarios for a European participation in human
      exploration and to estimate their influence on the life sciences and life support
      requirements; (ii) for selected mission scenarios, to critically assess the
      limiting factors for human health, wellbeing, and performance and to recommend
      relevant countermeasures; (iii) for selected mission scenarios, to critically
      assess the potential of advanced life support developments and to propose a
      European strategy including terrestrial applications; (iv) to critically assess
      the feasibility of existing facilities and technologies on ground and in space as
      testbeds in preparation for human exploratory missions and to develop a test plan
      for ground and space campaigns; (v) to develop a roadmap for a future European
      strategy towards human exploratory missions, including preparatory activities and
      terrestrial applications and benefits. This paper covers the part of the HUMEX
      study dealing with lunar missions. A lunar base at the south pole where long-time
      sunlight and potential water ice deposits could be assumed was selected as the
      Moon reference scenario. The impact on human health, performance and well being
      has been investigated from the view point of the effects of microgravity (during
      space travel), reduced gravity (on the Moon) and abrupt gravity changes (during
      launch and landing), of the effects of cosmic radiation including solar particle
      events, of psychological issues as well as general health care. Countermeasures
      as well as necessary research using ground-based test beds and/or the
      International Space Station have been defined. Likewise advanced life support
      systems with a high degree of autonomy and regenerative capacity and synergy
      effects were considered where bioregenerative life support systems and
      biodiagnostic systems become essential. Finally, a European strategy leading to a
      potential European participation in future human exploratory missions has been
      recommended.

PMID- 14696590
TI  - Strong magnetic field effect on the dissolution process of tetragonal lysozyme
      crystals.
AB  - Either a homogeneous or inhomogeneous magnetic field has been known to dampen the
      protein crystal growth. To date the mechanism is not clear. However, it was
      generally proposed that the magnetic field may dampen the convection in the
      solution, resulting in a reduced crystal growth rate and possibly a good crystal
      quality, similar to the case of protein crystal growth in space. To understand
      the mechanism of the magnetic field effect on protein crystal growth, further
      explorations on the magnetic field effect on protein solution, on the processes
      of crystal growth and dissolution, and on different crystallization (solution)
      systems, should be valuable. In this paper we present our recent efforts to study
      magnetic field effects on the dissolution processes of tetragonal lysozyme
      crystals under a strong magnetic field. A layer of oriented tetragonal lysozyme
      crystals was prepared under a temperature gradient and magnetic field, after that
      the crystals were dissolved by increasing the temperature of the solution. The
      lysozyme molecules will diffuse upwards due to the steep concentration gradient
      at the lower side of the cell caused by the dissolution. The evolution of the
      concentration in the solution was measured in-situ using a Mach-Zehnder
      interferometer. The results confirmed that the dissolution process of the
      crystals was slowed by the magnetic field. Judging from the concentration
      evolution versus time at different positions in the solution, we concluded that
      the apparent diffusion coefficient of lysozyme molecules was decreased by the
      magnetic field. The results were discussed using a suspended crystal model in the
      initial dissolution stage.

PMID- 14696591
TI  - A Controllable and Observable Protein Cystallization Facility.
AB  - A Controllable and Observable Protein Crystallization Facility (ACOP) was
      developed in 1999 for space experiment in the Get Away Special canister of Space
      Shuttle. To regulate the vapor diffusion rate, in a crystallization chamber, five
      cells each containing precipitant solution of different concentrations, exposed
      to one protein cell in turn. Five layers of chambers were overlapped coaxially.
      The crystallization process was observed and recorded by digital cameras.
      Structure of facility and result of image sequence were given.

PMID- 14696592
TI  - Short message service (SMS): a useful communication tool for surgeons.

PMID- 14696593
TI  - Joint British Association of Dermatologists and U.K. Cutaneous Lymphoma Group
      guidelines for the management of primary cutaneous T-cell lymphomas.

PMID- 14696594
TI  - Industrial hygienists: who we are, priorities, goals, limitations.

PMID- 14696595
TI  - [As the eyes learned to speak].

PMID- 14696596
TI  - [What you should be aware of when changing your computer system--II].

PMID- 14696597
TI  - Medicare physician payment: practice expense.

PMID- 14696598
TI  - [Transparent ophthalmological practice].

PMID- 14696599
TI  - Psychiatry in pictures. Annie Altschul teaching psychiatric nurses, 1950's,
      Bethlem Hospital.

PMID- 14696600
TI  - Precedents for hospice and surrogate decision-making in Jewish law.

PMID- 14696601
TI  - Rapid nongenomic aldosterone effects in the human forearm?

PMID- 14696602
TI  - The case of the British conjoined twins.

PMID- 14696603
TI  - Animals in psychology education and student choice.
AB  - This article identifies some of the important issues that underlie student
      teacher conflicts regarding animal experimentation and dissection in psychology
      education. Understanding the reasons why students object to animal laboratories,
      why some teachers may refuse students access to non-animal alternatives, and why
      other teachers support student choice is an important first step in resolving
      student-teacher disputes regarding the use of animals in the psychology
      classroom. The article discusses why establishing an openly declared student
      choice policy at schools that use animals in psychology education is a reasonable
      thing to do and describes how a student choice policy works in practice.

PMID- 14696604
TI  - The future-like-ours argument, personal identity, and the twinning dilemma.

PMID- 14696605
TI  - Abortion, autonomy, and control over one's body.

PMID- 14696606
TI  - United Nations urged to ban all human cloning.

PMID- 14696607
TI  - Older women and mercy killing.

PMID- 14696609
TI  - Prenatal diagnosis--discrimination, deliverance or democracy?
AB  - Prenatal diagnosis utilizes invasive procedures such as amniocentesis, chorionic
      villus sampling, cord blood sampling and pre-implantation genetic diagnosis.
      These techniques can diagnose serious foetal illnesses and this therefore
      provides valuable information to couples, helping them to prepare for the birth
      of an affected child. It also affords women the freedom to decide whether to
      terminate a pregnancy. The selective termination of foetuses with serious
      disabilities does not represent disability discrimination because women and
      parents are actually rejecting the disability, rather than the foetus itself.
      More significantly, the choice to abort a foetus with a serious illness or
      disability is an intensely private and personal exercise that does not and cannot
      be reflective of a wider public morality. Exactly the same can be said of the
      choice to selectively abort foetuses based solely on their sex. The private
      choice of women in this respect does not amount to the social devaluation of
      women. Firstly, it is an erroneous assumption that women in Australia prefer male
      babies. Secondly, even if there is a preference for male babies, banning prenatal
      sex selection would be treating just one of many symptoms of sexism, rather than
      curing the primary causes. The moral right of all women to reproductive freedom
      is an embodiment of their equal value in society.

PMID- 14696610
TI  - ACOG practice bulletin. Benefits and risks of sterilization. Number 46, September
      2003 (replaces Technical Bulletin Number 222, April 1996).

PMID- 14696611
TI  - Bibliography of Toxinology.

PMID- 14696612
TI  - 'On the sharpest horns of a dilemma': Re A (conjoined twins).

PMID- 14696613
TI  - Was Mary's death murder?

PMID- 14696614
TI  - Human beings, persons and conjoined twins: an ethical analysis of the judgement
      in Re A.

PMID- 14696615
TI  - Conjoined twins: separation as mutilation.

PMID- 14696616
TI  - Murder by design: the 'feel-good factor' and the criminal law.

PMID- 14696617
TI  - Whose life is it anyway?

PMID- 14696618
TI  - Killing off Mary: was the Court of Appeal right?

PMID- 14696619
TI  - Xenotransplantation: consent, public health and charter issues.
AB  - There is a growing body of literature and commentary analyzing the ethical and
      public policy concerns associated with xenotransplantation. While this technology
      holds great promise to provide an almost limitless supply of organs for
      transplantation, there remains grave concern about possible public health
      ramifications. As a result, it has been recommended that patients who undergo
      xenotransplantations will need to agree, inter alia, to a lifetime of close
      health monitoring, participation in an international database and autopsy upon
      death. It has been suggested that this agreement would transform the nature of
      informed consent into a "binding contract." Though such draconian measures are
      understandable given the magnitude of the risks involved, would existing common
      law and legislation allow their implementation? This paper analyzes relevant
      Canadian consent and public health law in the context of the xenotransplantation.
      Canada is a country with a particularly rich body of informed consent
      jurisprudence--jurisprudence firmly rooted (rightly or not) in the ethical
      principle of autonomy. In this climate, many of the suggested monitoring
      strategies would find little support from Canadian law. Before
      xenotransplantations proceed, policy makers must be sensitive to the legal
      barriers which exist to the implementation [of] effective public health measures.
      Effective surveillance programs will require novel approaches to consent and the
      enactment of specific public health laws.

PMID- 14696620
TI  - Engineering human tissue and regulation: confronting biology and law to bridge
      the gaps.
AB  - There are a number of difficulties confronting the regulation of human tissue
      engineered products, from the scientific, ethical and legal perspectives. Many of
      these issues are international in scope and any responses must consider the
      global implications of marketing and monitoring these products. The article
      argues that as tissue engineered products become more available regulatory
      authorities should not be pressured into adopting possibly inappropriate
      measures, but must consider all the factors relevant to human health, including
      the need for innovative regulatory mechanisms as well as innovative tissue
      products themselves.

PMID- 14696621
TI  - Chest X-ray quiz. Aspects of a post-operative chest X-ray.

PMID- 14696622
TI  - "Wrongful life" a la francaise.
AB  - A recent decision of the French supreme court has recognised what has been termed
      in the common law system, a "wrongful life" action. Intentionally provocative,
      the decision shows how the desire for equitable or "corrective" justice poses a
      threat not only to established legal principles on civil liability, but also to
      the ethical framework in which both the medical and legal professions must
      operate.

PMID- 14696623
TI  - Combining doxorubicin and liposomal anti-HER-2/NEU antisense
      oligodeoxynucleotides to treat HER-2/NEU-expressing MDA-MB-435 breast tumor
      model.
AB  - This study assessed the in vivo therapeutic activity of an antisense molecule
      targeted against HER-2/neu expressing mRNA. Antisense activity was evaluated in
      female SCID/Rag2m mice bearing subcutaneous tumors derived from HER-2/neu
      transfected MDA-MB-435 (MDA-MB-435(HER2)) cells, a transfected line derived from
      the human breast cancer MDA-MB-435 cell line. Animals were treated with free or
      liposome-encapsulated antisense. The area under the curve (AUC(0-24h)) of the
      liposomal formulated antisense was demonstrated to be more than 30-fold greater
      than that of free antisense following intravenous administration. Efficacy was
      determined by assessing changes in tumor growth rate as well as by an
      immunohistological end-point evaluating HER-2/neu expression. HER-2/neu protein
      expression was reduced in mice bearing HER-2/neu-transfected MDA-MB-435 tumors
      when treated with liposomal antisense. However, tumors in these mice grew at a
      faster rate than the control, a result that was interpreted to be a consequence
      of selection of a more rapidly proliferating HER-2/neu-negative subpopulation of
      cells. Effective control of the MDA-MB-435(HER2) tumors was achieved when
      antisense treatment was combined with doxorubicin. Tumors derived from animals
      treated with the combination of doxorubicin and the liposomal antisense against
      HER-2/neu exhibited no detectable levels of HER-2/neu expression. Antisense
      targeted against HER-2/neu mRNA was effective in reducing or eliminating HER
      2/neu protein expression, and when combined wtih doxorubicin treatment was
      efficacious in the treatment of mice bearing HER-2/neu-overexpressing human
      xenograft tumors.

PMID- 14696624
TI  - A time to regulate? Possible implications of European human rights law on
      abortion in Northern Ireland.
AB  - Since the introduction of the Abortion Act 1967 the legality and status of
      abortion in Northern Ireland, being excluded from the provisions of the 1967 Act,
      has remained shrouded in uncertainty. In light of the introduction of the Human
      Rights Act 1998, this article will explore whether this inconsistency in the UK
      is in breach of the provisions laid down in Articles 8 and 14. It will be shown
      that while compelling arguments can be built under these provisions, perhaps the
      most persuasive arguments in favour of law reform are the inequities that the
      current legal regime has perpetuated.

PMID- 14696625
TI  - Antitumor effect of stilbenoids from Vateria indica against allografted sarcoma S
      180 in animal model.
AB  - Dipterocarpaceous plants contain various resveratrol oligomers that exhibit a
      variety of biological activities, such as antibacterial and antitumor effects.
      Previously, we found that vaticanol C, a resveratrol tetramer, exhibits strong
      cytotoxicity against various tumor cell lines. In the present study, we examined
      the antitumor activity of the ethanol extract from the stem bark of Vateria
      indica, which has been traditionally used for health and healing diseases as
      Ayurveda in India. High-performance liquid chromatography analysis showed that
      the extract contains bergenin, hopeaphenol, vaticanol B, vaticanol C, and epsilon
      viniferin. The in vitro assay displayed the extract's anti-cancer activity
      against mouse sarcoma 180 cells (IC50=29.5 microM). In the animal study, the
      tumor growth of sarcoma S-180 cells subcutaneously allografted in DDY mice was
      significantly retarded by oral administration of the extract (30 or 100 mg/kg
      body weight: P < 0.001). The extract did not show significant toxicity to mice
      even at a dosage of 1000 mg/kg body weight by daily oral administration for 28
      days. These results demonstrated that the ethanol extract containing various
      stilbenoids from the stem bark of V. indica has the potent antitumor activity.

PMID- 14696626
TI  - The pre-implantation embryo revisited: a two-celled individual or two individual
      cells?

PMID- 14696627
TI  - The technical child: in vitro fertilization and the personal subject.

PMID- 14696628
TI  - The tragic case of Jodie and Mary: questions about separating conjoined twins.

PMID- 14696629
TI  - Impact of statins on novel risk markers.
AB  - Long-and-short term trials with the 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors (statins) have demonstrated significant reductions in
      cardiovascular and cerebrovascular events in patients with and without
      preexisting heart disease. Beyond improving the lipid profile, statins have
      additional effects that may contribute to their overall clinical benefit. Statin
      treatment appears to reduce global risk profile by affecting both novel and
      established lipid, inflammatory, and morphologic markers including low-density
      lipoprotein subclasses, lipoprotein (a), markers of endothelial function,
      inflammatory mediators, intima-media thickening, and coronary calcification.
      Although statins may be regarded as a rather homogeneous drug class in terms of
      biological activity, some agents feature unique properties that have beneficial
      effects on selected important risk matters.

PMID- 14696630
TI  - Carbachol prolongs ventricular repolarisation through nitric oxide release in an
      intact heart.
AB  - AIMS: The primary ain of this study was to investigate the effect of carbachol on
      ventricular repolarisation in an intact animal heart. METHODS: In five sheep,
      carbachol was administered to the left circumflex coronary artery (LCX) at 1.0
      and 2.5 micromol/ml/min respectively for 3 min. Multiple unipolar ECGs were
      acquired from the epicardium of LCX territory. Administration of carbachol at 2.5
      micromol/ml/min was also repeated after pre-treatment with nitro-L-arginine (20
      mg/kg), a nitric oxide synthase inhibitor. RESULTS: Carbachol at 1.0 or 2.5
      micromol/ml/min resulted in a T wave inversion and ARI prolongation in the LCX
      territory. The increase in ARI at 1.0 and 2.5 micromol/ml/min was 38 +/- 17 and
      58 +/- 14 ms respectively (p<0.05). T wave inversion and ARI prolongation at 2.5
      micromol/ml/min was diminished by pre-treatment with nitro-L-arginine.
      CONCLUSIONS: Carbachol results in a dose-dependent prolongation in ventricular
      repolarisation in this open-chest animal model. This effect is partially mediated
      by endogenous nitric oxide.

PMID- 14696631
TI  - Nature of the placebo effect.

PMID- 14696632
TI  - Effects of trimetazidine on submaximal exercise test in patients with acute
      myocardial infarction.
AB  - BACKGROUND: It was demonstrated that the novel metabolic agent, trimetazidine,
      could lessen the incidence and severity of angina, whether used in monotherapy or
      combination. Although the animal studies demonstrated that trimetazidine reduces
      myocardial infarct size anf improves recovery of mechanic function after
      ischemia, little is known on the potential benefits of trimetazidine in patients
      with myocardial infarction (AMI). The aim of this study was to evaluate the
      efficacy of trimetazidine on AMI by sub-maximal exercise test. METHODS: A double
      blind crossover trimetazidine versus placebo trial was carried out in 44 patients
      with AMI. Patients with randomly allotted into trimetazidine (23 patients) or
      placebo (21 patients) for 5 days and underwent an initial sub-maximal exercise
      test. Exercise tests according to the modified Bruce protocol were performed.
      Exercise end points included completion of stage II or 75% of maximum predicted
      heart rate whichever came first. An average 12-lead ECG was obtained at rest,
      every minute during exercise, at the onset of anginal symptoms, at the onset of 1
      mm ST segment depression, at peak exercise and every 2-minute during recovery.
      After the initial exercise tests, study groups resumed the drugs in the opposite
      order for 4 to 5 days and underwent a second sub-maximal exercise test. RESULTS:
      Exercise induced ST segment depression was noted in 17 patients (38.6%) receiving
      placebo. However, exercise induced ST-segment depression was observed in 8
      patients (18.1%) taking TMZ. Positive exercise test results were significantly
      higher on placebo group than TMZ group (p=0.018). Additionally, trimetazidine
      prolonged the time to 1-mm ST-segment depression (6.1 +/-0.5 vs 4.9 +/-0.4, P<
      0.031) and exercise duration (7.2+/-0.9 vs 5.8 +/-0.9, p<0.025). CONCLUSION:
      Trimetazidine therapy improves the exercise capacity and reduces evidence
      ischemia derived from sub-maximal post-infarction exercise testing.

PMID- 14696633
TI  - Colon cancer and the Western diet.

PMID- 14696634
TI  - DNA repair in skin cancer prevention.

PMID- 14696635
TI  - More evidence for green tea's unusual chemoprevention activity.

PMID- 14696636
TI  - Eat your garlic!

PMID- 14696637
TI  - Low-dose systemic phosphodiesterase III inhibitor pimobendan combined with
      prostacyclin therapy in a patient with severe primary pulmonary hypertension.
AB  - Pimobendan, an oral inotropic drug with phosphodiesterase III-inhibitory
      activity, induces cAMP-dependent relaxation of vascular smooth muscle in the
      pulmonary artery, as well as in the systemic cardiovascular system. We report
      here a patient with severe primary pulmonary hypertension (PPH), who had
      developed right heart failure (New York Heart Association functional class IV)
      despite uptitrated intravenous epoprostenol, and who was treated with extremely
      low-dose (0.625-1.25 mg daily) pimobendan as an adjunct to prostacyclin therapy.
      The combination therapy of low-dose pimobendan, prostacyclin, intravenous
      epoprostenol and oral beraprost has been continued for over 2 years without
      occurrence of fatal arrhythmia, and her six-minute walk test has exceeded 400 m.
      We suggest that low-dose pimobendan may enhance the hemodynamic effect of
      prostacyclin in severe PPH.

PMID- 14696638
TI  - Cancer-related fatigue syndrome.

PMID- 14696640
TI  - Transient intraventricular conduction delay associated with concurrent intake of
      propafenone and antineoplastic agents.
AB  - An 82-year old man was admitted with acute pulmonary edema. Myocardial ischemia
      and electrolyte abnormalities were excluded and he responded promptly to
      frusemide, nitrates and morphine. On admission, the duration of the QRS interval
      was markedly abnormal at 240 ms with a nonspecific intraventricular conduction
      defect pattern, of left bundle branch block type. This finding was not present
      three weeks prior to his admission, and was felt to be the result of drug
      interaction between propafenone and antineoplastic agents, as evidenced by
      resolution of the clinical and electrocardiographic picture after discontinuation
      of these agents.

PMID- 14696641
TI  - Genetic information: what is the patient's family entitled to know?

PMID- 14696642
TI  - Traditional Tibetan health care.

PMID- 14696643
TI  - Has the CACR lived up to its mandate?

PMID- 14696644
TI  - Fetal intervention: Halacha's response to a new bioethical dilemma.

PMID- 14696645
TI  - The individual, health hazardous lifestyles, disease and liability.

PMID- 14696646
TI  - Devolution and distrust: managed care and the resurgence of physician power and
      authority.

PMID- 14696647
TI  - Racial distinctions in medicine.

PMID- 14696648
TI  - Rethinking legislative consent law?

PMID- 14696650
TI  - Tracking health care costs: trends slow in first half of 2003.
AB  - This Data Bulletin is based on data from the Milliman USA Health Cost Index (HCI)
      ($0 deductible), which is designed to forecast claims trends faced by private
      insurers and the U.S. Bureau of Labor Statistics' National Compensation Survey to
      track hourly compensation costs for nurses and Producer Price Index for general
      medical and surgical hospitals to track hospital prices. The HCI classifies
      spending on services performed in freestanding facilities in its hospital
      outpatient category, which is consistent with how insurers classify such
      services. Due to data limitations, the HCI includes spending for Medicaid and
      uninsured patients, which can cause HCI trends to differ from privately insured
      trends. The authors have adjusted the HCI estimates to remove the effect of
      distinct Medicaid hospital price trends. As with most economic data, the HCI is
      subject to periodic retroactive revisions.

PMID- 14696651
TI  - Patient cost sharing: how much is too much?
AB  - Responding to successive years of double-digit health insurance premium
      increases, employers continue to restructure health benefits to slow the rise in
      company costs by increasing patients' financial stake in their care. A new Center
      for Studying Health System Change (HSC) study examines how increased patient cost
      sharing through higher deductibles, copayments and coinsurance raises patients'
      out-of-pocket costs. Increased patient cost sharing creates more financial
      burdens for seriously ill and low-income workers. Concerns about financial
      hardships for seriously ill and low-income workers may limit employers' ability
      to slow rising premiums through increased patient cost sharing.

PMID- 14696649
TI  - WISP3 and RhoC guanosine triphosphatase cooperate in the development of
      inflammatory breast cancer.
AB  - BACKGROUND: Inflammatory breast cancer (IBC) is the most lethal form of locally
      advanced breast cancer. We found concordant and consistent alterations of two
      genes in 90% of IBC tumors when compared to stage matched, non-IBC tumors:
      overexpression of RhoC GTPase and loss of WISP3. Further work revealed that RhoC
      is a transforming oncogene for HME cells. Despite the aggressiveness of the RhoC
      driven phenotype, it does not quantitatively reach that of the true IBC tumors.
      We have demonstrated that WISP3 has tumor growth and angiogenesis inhibitory
      functions in IBC. We hypothesized that RhoC and WISP3 cooperate in the
      development of IBC. METHODS: Using an antisense approach, we blocked WISP3
      expression in HME cells (HME/AS WISP3). Cellular proliferation and anchorage
      independent growth were determined using the MTT assay and the anchorage
      independent growth in soft agar assay. VEGF was measured in the conditioned media
      of the HME/ AS WISP3 by ELISA. RESULTS: Antisense inhibition of WISP3 expression
      in HME cells increased the levels of RhoC mRNA and increased cellular
      proliferation, anchorage independent growth and secretion of VEGF in these cells.
      Conversely, restoration of WISP3 expression in the highly malignant IBC cell line
      SUM149 was able to decrease the expression of RhoC protein. CONCLUSION: WISP3
      modulates RhoC expression in HME cells and in the IBC cell line SUM149, and
      provide further evidence in support that these two genes act in concert to give
      rise to the highly aggressive IBC phenotype. We propose a model of this
      interaction as a starting point for further investigations.

PMID- 14696652
TI  - Promoting maternal health in the workplace.

PMID- 14696653
TI  - The changing face of implant dentistry.

PMID- 14696654
TI  - Placement of autogeneic bone chips or bovine bone mineral in guided bone
      augmentation: a rabbit skull study.
AB  - PURPOSE: Our primary aim was to use a rabbit guided bone augmentation model to
      evaluate whether use of autogeneic bone grafts or bovine bone mineral (BBM)
      combined with a space-making barrier enhances bone augmentation compared with a
      barrier alone. MATERIALS AND METHODS: Sixteen rabbits were studied. In each
      rabbit, 2 titanium cylinders, each with 1 titanium lid, were placed
      subcutaneously in perforated slits made in the cortical bones, with their open
      ends facing the parietal bones. One cylinder was left empty and the other was
      filled with either autogeneic skull bone chips or BBM. Bone labels were injected
      after 4 and 11 weeks. After 12 weeks, the animals were sacrificed to obtain
      ground sections for histology and histomorphometry. RESULTS: Significantly more
      tissue was augmented in the 2 test groups than in the control group. Most of the
      autografts were resorbed, leaving only minute amounts in the upper third of the
      cylinders. Slender new bone trabeculae were distributed mainly from the
      contiguous bone plate that had no contact with the remaining graft material. In
      the BBM group, most of the BBM remained evenly distributed in the cylinder. In
      the upper third of the cylinder, the BBM was surrounded by soft connective
      tissue, while in the lower two thirds, mainly mineralized bone enclosed the BBM.
      Equal amounts of mineralized bone were found in both test groups. Comparisons of
      contact between bone and BBM on one hand and bone and bone cylinder wall on the
      other revealed that the greatest bone contact was with the BBM in the lower third
      of the cylinder. In the middle and upper third of the cylinder, bone-BBM contact
      and bone-cylinder wall contact were similar. Fluorescent label intensity was
      higher in the autograft group than in the BBM group. In all 3 groups the
      intensity of the early label was similar to that of the late label, indicating
      that the graft materials do not seem to retard mineralization. DISCUSSION: BBM
      was found to promote as much new bone as did autogeneic bone. In addition, BBM
      appears to have at least the same osteoconductive properties as titanium,
      provided BBM is contained in a stable environment. CONCLUSIONS: Placement of
      autogeneic bone or BBM in conjunction with a stiff space-making barrier generated
      more tissue than a barrier only. In this model, autogeneic bone chips and BBM
      augmented similar amounts of new mineralized bone.

PMID- 14696655
TI  - Effects of local administration of growth hormone in peri-implant bone: an
      experimental study with implants in rabbit tibiae.
AB  - PURPOSE: The objective of this study was to evaluate the qualitative and
      quantitative differences that could appear in newly formed peri-implant bone
      around Screw-Vent implants placed in rabbit tibiae when treated with local
      administration of growth hormone (GH). MATERIALS AND METHODS: Eight New Zealand
      rabbits were randomly divided into 2 groups: the experimental group, which
      received 4 IU of GH in the form of lyophilized powder added to the ostectomy site
      before implant placement, and the control group, which did not receive GH before
      implant placement. Animals were sacrificed 2 weeks later, and histologic sections
      were obtained for histomorphometry and observation under light microscopy.
      RESULTS: The sections in the GH-treated group presented enhanced growth of new
      trabeculae from the periosteal tissue, and the bone-to-implant contact in the
      experimental group was significantly greater (P < .05). DISCUSSION: Local
      administration of GH stimulated a more dramatic effect than that seen previously
      with systemic GH administration, prompting growth from both the periosteum and
      endosteum. CONCLUSIONS: Local administration of GH at the time of implant
      placement could enhance peri-implant bone reaction.

PMID- 14696656
TI  - Immediate placement of implants into periodontally infected sites in dogs. Part
      2: A fluorescence microscopy study.
AB  - PURPOSE: Polychromatic sequence labeling of bone was used to study the effect of
      periodontal infection on the immediate placement of Frialit-2 implants. MATERIALS
      AND METHODS: In the surgical first phase, periodontitis was induced with
      ligatures involving the mandibular premolars of 5 mongrel dogs, and the
      contralateral teeth were used as controls (received only prophylaxis). After 3
      months, the second phase was initiated and 40 implants were placed in the alveoli
      of both experimental and control teeth. During the healing period, fluorescent
      bone markers were injected to study bone formation around the implants. The dyes
      were injected in the following sequence: oxytetracycline hydrochloride at 3 days
      after implant placement, calcein green 4 weeks after implant placement,
      oxytetracycline 8 weeks after implant placement, and alizarin red S 3 days before
      sacrifice. Following a healing period of 12 weeks, the animals were euthanized
      and the hemimandibles were removed, dissected, fixed, and prepared for
      histomorphometic analysis of the percentage of each bone marker present. RESULTS:
      Fluorescence microscopy showed a similar sequence of bone remodeling (Mann
      Whitney test) for both groups: experimental group, 9% bone formation at 3 days,
      29% at 4 weeks, 21.6% at 8 weeks, and 52% at 12 weeks; control group, 14% at 3
      days, 35.2% at 4 weeks, 32.3% at 8 weeks, and 45.8% at 12 weeks. DISCUSSION:
      Remodeling in both groups had similar characteristics in the degree of bone
      formation. CONCLUSIONS: It was concluded that periodontal disease does not affect
      bone remodeling around immediate implants. Although the healing in periodontally
      infected sites was slower initially, it reached the levels of the non-diseased
      sites after 12 weeks.

PMID- 14696657
TI  - Nitric acid passivation does not affect in vitro biocompatibility of titanium.
AB  - PURPOSE: In general, both chemical composition and surface features of implants
      affect cell response. The aim of this study was to evaluate the effect of
      titanium (Ti) passivation on the response of rat bone marrow cells, considering
      cell attachment, cell morphology, cell proliferation, total protein content,
      alkaline phosphatase (ALP) activity, and bonelike nodule formation. MATERIALS AND
      METHODS: Cells were cultured on both commercially pure titanium (cpTi) and
      titanium-aluminium-vanadium alloy (Ti-6Al-4V) discs, either passivated or not.
      For attachment evaluation, cells were cultured for 4 and 24 hours. Cell
      morphology was evaluated after 4 days. After 7, 14, and 21 days, cell
      proliferation, total protein content, and ALP activity were evaluated. Bonelike
      nodule formation was evaluated after 21 days. Data were compared by analysis of
      variance and the Duncan multiple range test. RESULTS: Cell attachment, cell
      morphology, cell proliferation, total protein content, ALP activity, and bonelike
      nodule formation all were unaffected by Ti composition or passivation. DISCUSSION
      AND CONCLUSION: Although the protocol for passivation used here could interfere
      with the pattern of ions released from Ti-6Al-4V and cpTi surfaces, the present
      study did not show any effect of this surface treatment on in vitro
      biocompatibility of Ti as evaluated by osteoblast attachment, proliferation, and
      differentiation.

PMID- 14696658
TI  - Long-term evaluation of submerged and nonsubmerged ITI solid-screw titanium
      implants: a 10-year life table analysis of 468 implants.
AB  - PURPOSE: Submerged and nonsubmerged ITI solid-screw titanium implants were
      followed retrospectively from 1989 to 1993 and prospectively from 1994 on to
      analyze long-term prognosis in partially and fully edentulous patients. MATERIAL
      AND METHODS: A total of 468 implants were consecutively inserted in 191 patients
      from 1989 to 1998. Two hundred twenty-eight successfully integrated fixed
      restoration implants and 238 with removable restorations were restored following
      a healing period of 4 to 6 months (9 months in sinus floor elevation sites). From
      1994 on all implants inserted were documented annually up to 9 years. During
      examination the clinical status of the implants was analyzed and evaluated
      according to predefined criteria of success and this allowed the calculation of
      10-year cumulative survival and success rates for 468 implants. RESULTS: Two
      implants (0.43%) did not successfully integrate during the healing period, and 8
      implants (1.7%) were classified as failures during follow-up (1 late failure
      under load, 7 with a progressive bone loss from 1 to 3 threads). Including 68
      implants in subjects who dropped out (with a dropout rate of 14.4%), the 10-year
      cumulative survival and success rates were 99.2% and 96.4%, respectively.
      DISCUSSION: Over the course of this long-term study, osseointegrated implants,
      once used as a last possible solution, became nearly standard in cases of single
      tooth implants because of the high rate of long-term success. Life table analysis
      not only determines whether an implant is functioning, it also makes a statement
      about its clinical status according to strict success criteria. CONCLUSION: The
      study demonstrated that ITI solid-screw titanium implants achieved success rates
      above 95% in a clinical center for an observation period of up to 10 years.

PMID- 14696659
TI  - Randomized multicenter comparison of 2 IMZ and 4 TPS screw implants supporting
      bar-retained overdentures in 425 edentulous mandibles.
AB  - PURPOSE: Two treatment concepts for implant-supported bar retention of mandibular
      overdentures-2 intramobile cylinder (IMZ) implants and a Dolder bar and 4
      titanium plasma-sprayed (TPS) screw implants and an angulated bar-were compared
      in a randomized controlled clinical trial with respect to postprosthetic efficacy
      and safety. MATERIALS AND METHODS: Four hundred twenty-five patients with
      edentulous mandibles were enrolled; 212 were randomized to TPS implants (control
      group) and 213 to IMZ implants (test group). Endpoints were occurrences of
      postprosthetic integration deficiency (ID), functional deficiency (FD), and
      complications. The trial was sized to detect a 10% difference in 5-year ID-free
      postprosthetic system lifetime with a power of 80%. RESULTS: With 340 protocol
      completed cases, the trial achieved its predetermined power. The 2 systems did
      not show statistically significant differences in occurrences of postprosthetic
      ID and FD; 5-year occurrence-free postprosthetic system lifetime probabilities
      were estimated as 42.5% with IMZ and 42.8% with TPS, for ID; and as 82.6% with
      IMZ and 87.2% with TPS, for FD. However, at 3 to 6 months after surgery, mean
      Periotest values were significantly higher (P = .0001 without adjustment) with
      IMZ implants (5.6, SD 4.2) than with TPS implants (0.8, SD 4.3). TPS implants
      showed a higher incidence of inflammation and recession, while IMZ implants had a
      higher incidence of implant fracture after functional loading. DISCUSSION: The
      system-wise approach overcomes potential bias with implant-wise analyses. A
      combination of radiographic and clinical criteria distinguishes between desirable
      integration and functional anchorage. The in situ survival rates at 5 years in
      this study (95% for IMZ, 92% for TPS) match rates reported in the literature.
      CONCLUSION: This study demonstrated equivalent efficacy of 2 IMZ cylinders and 4
      TPS screws in implant-supported, bar-retained mandibular overdentures and
      indicated a higher rate of complications with the TPS screw implants.

PMID- 14696660
TI  - Complications of dental implants: identification, frequency, and associated risk
      factors.
AB  - PURPOSE: This study sought to identify the types, frequencies, and risk factors
      associated with complications following placement of dental implants. It was
      hypothesized that one or more factors could be identified that are associated
      with an increased risk for complications and may be modified by the clinician to
      enhance outcome. MATERIALS AND METHODS: A retrospective cohort study design was
      used that included patients who received Bicon implants (Bicon, Boston, MA)
      between 1992 and 2000. Predictor variables were grouped into demographic, medical
      history, implant-specific, anatomic, prosthetic, and reconstructive categories.
      Complications were grouped into inflammatory, prosthetic, operative, and major or
      minor categories. Cox proportional hazards regression models were developed to
      identify risk factors for complications. RESULTS: The sample was composed of 677
      patients. The overall frequency of implant complications was 13.9% (10.2%
      inflammatory, 2.7% prosthetic, 1.0% operative), of which 53% were minor. The
      multivariate Cox model revealed that smoking, use of 1-stage implants, and
      reconstructive procedures were statistically associated with an increased risk
      for overall complications (P < or = .05). The median duration of follow-up was
      13.1 months (range 0 to 85.6 months). DISCUSSION: A lower frequency of
      complications was found compared to mean frequencies calculated from past
      reports. Investigations examining the influence of smoking and reconstructive
      procedures on implant complications are recommended. CONCLUSION: Of the 3 factors
      associated with an increased risk for complications, tobacco use and implant
      staging may be modified by the clinician to enhance outcome.

PMID- 14696661
TI  - Four-year follow-up of larger-diameter implants placed in fresh extraction
      sockets using a resorbable membrane or a resorbable alloplastic material.
AB  - PURPOSE: The aim of this randomized study was to evaluate and compare the long
      term success rates of cylindric, screw-type titanium implants with a larger
      diameter (5.9 mm) that were placed in fresh extraction sockets in association
      with resorbable bone substitutes or a resorbable membrane. MATERIALS AND METHODS:
      Eighty-three partially edentulous adult patients, selected from among those
      treated in 1997 and 1998 at the San Raffaele Institute in whom 1 or more implants
      had been placed into fresh posterior mandibular or maxillary sockets, were
      included in the study. A total of 111 implants were placed, 36 in mandibles and
      75 in maxillae. Fifty-six implants were placed in combination with resorbable
      hydroxyapatite (HA group) and 55 with a resorbable membrane (MR group). Intraoral
      radiographs and follow-up examinations, including verification of implant
      stability via the Periotest, were carried out at second-stage surgery 3, 6, 9,
      and 12 months later; and then annually up to 4 years after placement of the
      definitive restoration. The radiographic examination was conducted by means of a
      standardized procedure to verify osseointegration. RESULTS: There was 100%
      attendance at the follow-up examination after 4 years. At second-stage surgery,
      which was performed after 4 to 6 months' healing time, none of the implants
      showed any signs of mobility, peri-implantitis, or bone loss. Two implants failed
      in the MR group, one at 3 months and one at 9 months after placement; 1 implant
      failed in the HA group at 4 months after placement. After 4 years, the implant
      success rate was 97.3% (108 of 111 implants were considered successful). The
      success rate did not differ significantly between the HA group (98.2%) and the MR
      group (96.4%). DISCUSSION: The use of larger-diameter implants served to minimize
      the anatomic discrepancies that would have evolved when substituting a molar with
      a standard-diameter implant. According to the accepted criteria for success, the
      5-year success rate should be at least 85%; therefore both methods may be
      considered satisfactory. CONCLUSION: Implants placed in combination with a
      resorbable allogeneic material or with a resorbable membrane provided predictable
      long-term results when restored with a fixed partial denture.

PMID- 14696662
TI  - Evaluation of the ITI Morse taper implant/abutment design with an internal
      modification.
AB  - PURPOSE: The purpose of this study was to compare internal Morse taper
      connections in 2 separate modes: repeated torque/reverse-torque values and
      compressive bending at a 30-degree off-axis angle. MATERIALS AND METHODS: Three
      sample groups (n = 12 in each group)--a solid-screw implant paired with a 5.5-mm
      solid abutment (SSI), a synOcta implant with a 5.5-mm solid abutment (SOI), and a
      synOcta implant with a synOcta 5.5-mm solid abutment (SOSA)--were torqued to 35
      Ncm, and the reverse torque to remove the abutment was recorded. This was
      repeated for 3 trials. Additionally, the sample groups were loaded 30 degrees off
      axis, and the ultimate compressive values were recorded. RESULTS: There was a
      significant difference in the initial reverse-torque values. The SOSA setup
      showed significantly lower torque than the SOI and SSI setups (P < .05). In
      addition, the compressive bending test showed that the SOSA setup was
      significantly different (P < .05) from the SSI and SOI setups. Radiographic
      survey of the test groups following compressive bending revealed no implant
      fractures, but bending of the implant-abutment complex occurred. DISCUSSION: The
      alteration within the Morse taper did not reduce the strength of the implant
      abutment connection, ie, the reduction in surface area did not significantly
      reduce the torque properties or tensile properties. The new 2-piece synOcta 5.5
      mm solid abutment was shown to have a stronger implant-abutment connection when
      torqued down a second time. CONCLUSIONS: In this in vitro study, alteration of
      the Morse taper with an internal octagon indexing did not significantly reduce
      the strength of the implant connection. Sufficient strength was exhibited, which
      would indicate this implant-abutment design for anterior as well as posterior
      edentulous sites.

PMID- 14696663
TI  - Rotational panoramic versus intraoral rectangular radiographs for evaluation of
      peri-implant bone loss in the anterior atrophic mandible.
AB  - PURPOSE: In patients with atrophic mandibles, elevation of the floor of the mouth
      often prevents intraoral rectangular radiography for longitudinal follow-up
      studies, while extraoral techniques such as panoramic radiographs tend to produce
      distorted views of the interforaminal region. In this study, intraoral
      rectangular radiographs and panoramic radiographs were compared for their
      accuracy in evaluating peri-implant bone loss. MATERIALS AND METHODS: In a recall
      program, 22 patients with 88 screw-type implants (44 MKII and 44 Frios) were
      followed. Interforaminal marginal bone loss was evaluated by extraoral
      orthopantomograms and by intraoral rectangular radiographs. In addition, pocket
      depth, Periotest readings, and bleeding on probing were recorded. For statistical
      analysis, the Spearman coefficient of correlation was used. The effects on bone
      loss and clinical variables were computed with a mixed model and the Bland and
      Altman method. RESULTS: Computed as least square means, the mean difference
      between panoramic radiographs (2.4 +/- 0.2 mm for MKII implants and 1.6 +/- 0.2
      mm for Frios implants) and intraoral radiographs (2.6 +/- 0.2 mm and 1.4 +/- 0.2
      mm, respectively) was 0.2 mm (range, 0.1 to 0.8 mm). DISCUSSION: In this study,
      the 2 imaging techniques were comparable clinically in terms of the precision
      with which they could be used to measure marginal bone loss. CONCLUSION: For
      highly atrophic mandibles with unfavorable imaging conditions, rotational
      panoramic radiographs can be a useful alternative to intraoral small-format
      radiographs for evaluating peri-implant bone loss.

PMID- 14696664
TI  - Comparison of implant-retained mandibular overdentures and conventional complete
      dentures: a 10-year prospective study of clinical aspects and patient
      satisfaction.
AB  - PURPOSE: The aim of this prospective randomized clinical trial was to evaluate 10
      years of treatment of patients receiving a mandibular implant-retained
      overdenture (IRO) or a conventional complete denture (CD). MATERIALS AND METHODS:
      One hundred twenty-one edentulous patients were treated with an IRO (2 endosseous
      implants, n = 61) or a conventional CD (n = 60). Clinical aspects and patient
      satisfaction were evaluated. One year after placement of the denture, unsatisfied
      patients of the CD group were given the opportunity to receive implants. RESULTS:
      In the IRO group, 4 implants were lost during the first year and 4 implants were
      lost during the next 4 years. Between 5 and 10 years, no implants were lost
      (survival rate: 93%). In the CD group, 24 patients (40%) chose an IRO between 1
      and 10 years. DISCUSSION: Patients in the IRO group were significantly more
      satisfied than patients in the CD group after 1 year (satisfaction score 8.3
      versus 6.6 on a scale of 1 to 10), after 5 years (7.4 versus 6.4), and after 10
      years (7.7 versus 6.8). CONCLUSION: The mean satisfaction score of the CD group
      (including patients who later received implants) was still lower than that of the
      IRO group, in spite of the opportunity for retreatment with IROs. Endosseous
      implants had a high survival rate after 10 years of follow-up.

PMID- 14696665
TI  - Reliability of preoperative planning of an image-guided system for oral implant
      placement based on 3-dimensional images: an in vivo study.
AB  - PURPOSE: The purpose of this study was to assess the reliability of the planning
      software of an image-guided implant placement system based on a mechanical device
      coupled with a template stabilized on soft tissue during surgery. MATERIALS AND
      METHODS: Thirty consecutive partially or completely edentulous patients were
      treated with the image-guided system. For each patient, a study prosthesis was
      fabricated and duplicated in acrylic resin and served as a scanning template.
      Axial images were obtained from a computerized tomographic scan and transferred
      to planning software that provides real 3-dimensional information to plan implant
      position. Once the final position of the implant was defined, preoperative data
      such as the size of implants and anatomic complications were recorded using the
      planning software. The scanning template was then drilled in that exact position
      by a drilling machine. During surgery, the drilled template was used as a drill
      guide. After implant placement, intraoperative data were recorded and
      statistically compared with the preoperative data using the Kendall correlation
      coefficient for qualitative data and the Kappa concordance coefficient for
      quantitative data. RESULTS: Agreement between the preoperative and intraoperative
      data was high for both implant size and anatomic complications. The Kendall
      correlation coefficient was 0.8 for the diameter and 0.82 for the length. The
      Kappa concordance coefficient was 0.87 for both dehiscence and bone graft, 0.88
      for osteotomy, and 1.0 for fenestration. DISCUSSION: In the few instances where
      planning was not perfect, implant placement was completed in a clinically
      acceptable manner. CONCLUSION: The results suggest that the image-guided system
      presented is reliable for the preoperative assessment of implant size and
      anatomic complications. It may also be reliable for flapless surgery.

PMID- 14696666
TI  - Clinical evaluation of short, machined-surface implants followed for 12 to 92
      months.
AB  - PURPOSE: Bone resorption following tooth loss often limits the quantity of bone
      available for implant placement. The purpose of the present study was to evaluate
      the clinical outcome of 10-mm or shorter machined-surface implants when used
      exclusively in the treatment of various forms of edentulism. MATERIALS AND
      METHODS: Two hundred sixty-nine screw-type Branemark System implants (Nobel
      Biocare), 10 mm or shorter, were placed in 111 consecutively treated patients. Of
      the total, 88.8% were placed in the mandible and 11.2% were placed in the
      maxilla; 95.2% were used to treat partially edentulous situations, including
      single-tooth losses, of which 96.6% were in the premolar and molar regions. The
      patients were followed for periods of 12 to 92 months. RESULTS: Of the 269 placed
      implants, 12 were lost. The overall survival rate was 95.5%. Bone quality 2 and 3
      (Lekholm-Zarb classification of 1985) was found in 88.8% of the treated sites.
      There was no statistical difference in the survival rate of the 10-mm implants
      when compared to the shorter series (P > .05) or between the various implant
      diameters. The mean marginal bone loss was 0.71 +/- 0.65 mm. DISCUSSION: The
      failure rate of 4.5% compares favorably with that of implants of different shape,
      surface characteristics, and length. Bone quality appeared to be the critical
      factor in implant survival, rather than bone quantity, in this patient series.
      CONCLUSIONS: This study supports the survival of short, machined-surface implants
      when used for the treatment of partial edentulism in bone of good quality.

PMID- 14696667
TI  - Modified technique using multiple zygomatic implants in reconstruction of the
      atrophic maxilla: a technical note.
AB  - Zygomatic implants have been in use since the 1990s for the treatment of patients
      with severely resorbed maxillae. Here, the authors present a modification of the
      standard zygomatic implant technique that uses up to 3 implants on each side of
      the maxilla for support of a dental prosthesis.

PMID- 14696668
TI  - Two-year follow-up of a patient with oligodontia treated with implant- and tooth
      supported fixed partial dentures: a case report.
AB  - Dental implants have become an accepted treatment modality for aging patients
      with either completely or partially edentulous arches. However, growing patients
      with congenitally missing primary and/or permanent teeth often need dental
      implant treatment, even before puberty, for optimum functional and/or
      psychosocial development. From a developmental perspective, dental implants
      cannot accompany the physiologic differentiation of the alveolar bone because of
      the difference in anchorage between an osseointegrated dental implant and a tooth
      in bone. Nevertheless, reports in the literature suggest that dental implants can
      be used successfully in partially and completely edentulous arches affected by
      congenital disorders such as ectodermal dysplasia. In this case report, a
      multidisciplinary team approach, which included an orthodontist, an oral surgeon,
      and prosthodontists, in the treatment of a patient with oligodontia is discussed.
      The orthodontic and prosthodontic treatment sequence, growth analysis from age 14
      to 18 years, and successful therapy of an implant associated with late failure is
      presented.

PMID- 14696669
TI  - What measures are needed to reduce the costs of implant treatment so as to render
      it more affordable for the average-income patient and generally increase the
      demand for care?

PMID- 14696670
TI  - Locally administered nerve growth factor suppresses ginsenoside Rb1-enhanced
      peripheral nerve regeneration.
AB  - A high-dose of nerve growth factor (NGF) mixed with ginsenoside Rb1 (GRb1) was
      encapsulated by collagen and placed in silicone rubber chambers, which were used
      to repair dissected Sprague-Dawley rat sciatic nerves with 15 mm gaps. Six weeks
      after surgery, no axons or Schwann cells were seen in these chambers. By
      comparison, nerves treated with collagen-GRb1 alone had regenerated axons and
      Schwann cells in their endoneurial areas. We suggest that excessive NGF may not
      promote but, rather, suppress developing nerves.

PMID- 14696672
TI  - Antioxidant activity of methanol extract of the lotus leaf (Nelumbo nucifera
      Gertn.).
AB  - In this study, hydrogen peroxide (H2O2)-mediated Caco-2 cytotoxicity was employed
      to investigate the potential antioxidant activity of the methanol extract from
      the lotus leaf (Nelumbo nucifera Gertn.). A dose-dependent protective effect
      against reactive oxygen species (ROS)-induced cytotoxicity was observed when Caco
      2 cells were treated with 10 mM H2O2 in combination with the methanol extract of
      the lotus leaf (0.1-0.3 mg/ml). However, no significant effect was found when co
      treating Caco-2 cells with 10 mM H2O2 and alpha-tocopherol. In vitro assay
      revealed that the extract exhibited scavenging activities on free radicals and
      hydroxyl radicals, and metal binding ability as well as reducing power, which may
      explain in part the mechanism behind the extract's ability to protect cells from
      oxidative damage. In addition, the extract also exhibited concentration-dependent
      antioxidant activities against hemoglobin-induced linoleic acid peroxidation and
      Fenton reaction-mediated plasmid DNA oxidation.

PMID- 14696671
TI  - Protective effect of shenqi-wan against H2O2-induced apoptosis in hippocampal
      neuronal cells.
AB  - The present study investigated whether Shenqi-wan possesses a protective effect
      against hydrogen peroxide (H2O2)-induced apoptosis of the hippocampal cell line
      HiB5. Through morphological and biochemical analyses, it was demonstrated that
      HiB5 cells treated with H2O2 exhibited several apoptotic features, while cells
      pre-treated with Shenqi-wan prior to H2O2 exposure showed a decrease in the
      occurrence of apoptosis. In addition, a patch clamp study revealed that Shenqi
      wan inhibited profoundly N-methyl-D-aspartic acid (NMDA) receptor-activated ion
      current in acutely dissociated hippocampal CA1 neurons. These results suggest
      that Shenqi-wan may exert its protective effect against H2O2-induced apoptosis
      via inhibition of NMDA receptors in hippocampal neuronal cells.

PMID- 14696673
TI  - Prevention of experimentally-induced gastric ulcers in rats by an ethanolic
      extract of "Parsley" Petroselinum crispum.
AB  - An ethanolic extract of Parsley, Petroselinum crispum (Mill.) Nym.ex A.W. Hill
      (Umbelliferae), was tested for its ability to inhibit gastric secretion and to
      protect gastric mucosa against the injuries caused by pyloric ligation,
      hypothermic restraint stress, indomethacin and cytodestructive agents (80%
      ethanol, 0.2 M NaOH and 25% NaCl) in rats. The extract in doses of 1 and 2 g/kg
      body weight had a significant antiulcerogenic activity on the models used.
      Besides, ethanol-induced depleted gastric wall mucus and non-protein sulfhydryl
      contents were replenished by pretreatment with Parsley extract. Acute toxicity
      tests showed a large margin of safety for the extract. The phytochemical
      screening of Parsley leaves revealed the presence of tannins, flavonoids, sterols
      and/or triterpenes.

PMID- 14696674
TI  - Suppressive effects of a Chinese herbal medicine qing-luo-yin extract on the
      angiogenesis of collagen-induced arthritis in rats.
AB  - Qing-Luo-Yin (QLY), a traditional Chinese herbal medicine for the treatment of
      rheumatoid arthritis, is a combination of the extracts of Sophora flavescens
      Ait., Phellodendron amurense Rupr., Sinomenium acutum Rehd. et Wils. and
      Dioscorea hypoglauca Palib. The suppressive effect of QLY on the development of
      angiogenesis was investigated in a rat model of collagen-induced arthritis (CIA).
      QLY (0.3 g/kg) was orally administered daily for 27 days. Neo-angiogenesis,
      pannus and cartilage damage, the expression of metalloproteinases (MMP)-3
      messenger RNA (mRNA) and the level of the tissue inhibitor of matrix
      metalloproteinase (TIMP)-1 in the synovium were examined by histology, in situ
      hybridization and immunohistochemiscal assays, respectively. It was observed that
      the articular morphological alterations, the over-expression of MMP-3 mRNA and
      the reduced production of TIMP-1 in CIA rats were significantly ameliorated by
      QLY. QLY performed about as effectively as tripterygium glycosidorum tablets (0.1
      g/kg) extracted from Tripterygium wilfordii Hook. f.. These results indicate that
      QLY exerts a suppressive effect on the angiogenesis of CIA rats, and suggest that
      the therapeutic effect of QLY could be due to restoring the balance of MMP-3 and
      TIMP-1 in rheumatoid synovium.

PMID- 14696675
TI  - Protective effect of Nigella sativa seeds against carbon tetrachloride-induced
      liver damage.
AB  - It has been reported that Nigella sativa oil possesses hepatoprotective effects
      in some models of liver toxicity. However, it is N. sativa seeds that are used in
      the treatment of liver ailments in folk medicine rather than its oil. Therefore,
      the aim of this study was to investigate the effect of the aqueous suspension of
      N. sativa on carbon tetrachloride (CCL4)-induced liver damage. Aqueous suspension
      of the seeds was given orally at two dose levels (250 mg/kg and 500 mg/kg) for
      five days. CCL4 (250 microl/kg intraperitoneally / day in olive oil) was given to
      the experimental group on days 4 and 5, while the control group was only treated
      with the vehicles. Animals treated with CCL4 showed remarkable centrilobular
      fatty changes and moderate inflammatory infiltrate in the form of neutrophil and
      mononuclear cells when compared to the controls. This effect was significantly
      decreased in animals pretreated with N. sativa. Histopathological or biochemical
      changes were not evident following administration of N. sativa alone. Serum
      levels of aspartic transaminase (AST), and L-alanine aminotransferase (ALT) were
      slightly decreased while lactate dehydrogenase (LDH) was significantly increased
      in animals treated with CCL4 when compared to the control group. LDH was restored
      to normal but ALT and AST levels were increased in animals pretreated with N.
      sativa. In conclusion, N. sativa seeds appeared to be safe and possibly
      protective against CCL4-induced hepatotoxicity. However, further studies may
      still be needed prior to supporting its use in folk medicine for hepatic
      diseases.

PMID- 14696676
TI  - Effects of oral administration of Gardeniae fructus extract and intravenous
      injection of crocetin on lipopolysaccharide- and prostaglandin E2-induced
      elevation of aqueous flare in pigmented rabbits.
AB  - The purpose of this study was to evaluate the effects of extracts of Coptidis
      rhizoma, Phellodendri cortex and Gardeniae fructus, which are medicinal herbs in
      Orengedoku-to (Huanglin-Jie-Du-Tang in Chinese), and crocetin (a major component
      of Gardeniae fructus) on experimental elevation of aqueous flare in pigmented
      rabbits. To produce aqueous flare elevation, 0.5 microg/kg lipopolysaccharide
      (LPS) was injected into the ear vein, or prostaglandin E2 (PGE2) 25 microg/ml,
      was applied to the cornea by means of a glass cylinder. Animals were pretreated
      by oral administration of 150 g/day of food containing 0.15% (w/w) extract powder
      of Coptidis rhizoma, 0.10% (w/w) extract powder of Phellodendri cortex or 0.15%
      (w/w) extract powder of Gardeniae fructus for 4 days, or by intravenous injection
      of crocetin, 0.3, 3, 30 or 300 microg/kg, 30 minutes before aqueous flare
      elevation. Aqueous flare was measured with a laser flare-cell meter. Aqueous
      flare intensity was expressed as the area under the curve (AUC) in arbitrary
      units. The AUC of LPS- and PGE2-induced aqueous flare elevation was 4685 and 1386
      arbitrary units, respectively. Pretreatment by oral administration of 0.15% (w/w)
      extract of Coptidis rhizoma or 0.10% (w/w) extract of Phellodendri cortex did not
      inhibit LPS-induced aqueous flare elevation. Pretreatment by oral administration
      of 0.15% extract of Gardeniae fructus suppressed LPS-induced aqueous flare
      elevation (AUC: 1411 arbitrary units). Pretreatment by intravenous injection of
      3, 30 or 300 microg/kg of crocetin-inhibited LPS-induced aqueous flare elevation
      in a dose-dependent manner. Pretreatment with 3 or 30 microg/kg of crocetin did
      not inhibit PGE2-induced aqueous flare elevation, but 300 microg/kg of crocetin
      inhibited PGE2-induced aqueous flare elevation (AUC: 918 arbitrary units).

PMID- 14696677
TI  - Effects of traditional Chinese medicines on murine bone metabolism in a
      microgravity environment.
AB  - We investigated the effects of three traditional Chinese medicine prescriptions
      on changes of bone metabolism in mice, using a gravity device to produce a
      microgravity environment. We found that Hochu-ekki-to (TJ-41) and Hachimi-jio-gan
      (TJ-7) suppress the increase in the ratio of serum Ca/P and the increase of
      calcium in urine. Moreover, TJ-41 and Shin-bu-to (TJ-30) reversed the increase of
      alkaline phosphatase activity (ALP), and TJ-41 also reversed the decrease of
      estradiol in the serum. The mechanism may be that the traditional Chinese
      medicines increased estradiol, causing the decrease of ALP, which induced the
      changes of Ca and P in serum, leading to a decreased excretion of Ca in urine. In
      this study, TJ-41 was effective in every parameter while TJ-7 and TJ-30 was
      effective on some parameters, showing that traditional Chinese medicines have
      specificities in the space environment. In conclusion, this study suggests that
      some traditional Chinese medicines may be beneficial for adaptation to a space
      environment.

PMID- 14696678
TI  - The evaluation of Chinese herbal medicine effectiveness on periodontal pathogens.
AB  - The aim of this study was to evaluate the effects of herbal medicines in treating
      periodontal diseases. Three Chinese herbal composites [Conth Su (CS), Chi Tong
      Ning (CTN) and Xi Gua Shuang (XGS)], widely used for prevention and treatment of
      periodontal diseases, and the major components of these composites were tested
      for their ability to: (1) alleviate disease progression of experimental
      periodontitis in hamsters, (2) inhibit bacterial growth, and (3) induce
      mutations. Our results indicate that in treating experimental periodontitis,
      there were no significant differences between the animal groups with or without
      the use of Chinese herbal medicines in terms of the degree of inflammation,
      alveolar bone resorption, and rate of repair. However, hamsters treated with CS
      presented earlier regenerative epithelium. CTN demonstrated superior bacterial
      inhibition ability among all tested herbs (MIC 0.025 g/ml); CS showed good anti
      bacterial abilities at a concentration of 0.05 g/ml. It is interesting to note
      that while both CS and CTN were capable of inhibiting bacterial growth, none of
      the individual herb components showed comparable bacterial inhibition abilities.
      None of the tested herbal composites or their components showed signs of inducing
      cell mutations using the Ames test. These results indicated that traditional
      Chinese herbal medicines, which have been used to treat periodontal diseases for
      hundreds of years by Chinese people, can effectively inhibit bacterial growth
      without causing cell mutation. Further investigation into their possible clinical
      applications in periodontal therapy is encouraged.

PMID- 14696679
TI  - Effects of Unkei-to on FSH, LH and estradiol in anovulatory young women with
      hyper- or hypo-functioning conditions.
AB  - Eight weeks treatment with Unkei-to induced a significant increase in plasma
      follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol levels
      in hyper- (robust) and hypo- (asthenia) functioning patients with first- and
      second-grade amenorrhea. We observed no significant differences in the rate of
      change of these hormones between hyper- and hypo-functioning patients. Ovulation
      occurred in 61.3% and 66.7% of patients with first-grade amenorrhea, and in 27.3%
      and 22.4% of patients with second-grade amenorrhea, respectively. No significant
      difference was observed in the ovulation rate after an 8-week treatment with
      Unkei-to between hyper- and hypo-functioning patients. These results indicate
      that Unkei-to is effective in improving gonadotropin and estradiol secretion in
      the treatment of either hyper- or hypo-functioning anovulatory women.

PMID- 14696680
TI  - Heterogeneity of Chinese medical herbs in Singapore assessed by fluorescence AFLP
      analysis.
AB  - There are conflicting records on the identity of Chinese medical herbs, and it is
      known that different plant materials are used under the same common names in
      different regions in China. However, there is no study on the genetic
      heterogeneity of medical herbs in any market outside of China. In this report,
      Chinese medical herbs under common names Radix Quinquefolii (American Ginseng or
      Xiyangshen), Radix Astragali (Huangqi), Radix Notoginseng (Tianqi), Coxtex
      Cinnamomum (Guipi), Radix Isatidis (Banlangen), Radix Codonopsis (Dangshen) and
      Radix Rehmannia (Shengdi) were collected from three independent herbal shops in
      Singapore and their DNAs were isolated and subjected to fluorescence Amplified
      Fragment Length Polymorphism (AFLP) analysis. While samples for Radix
      Quinquefolii and Radix Astragali were homogenous genetically [similarity index
      (SI) = 0.85-1.00] across the three shops, genetic heterogeneity was found for the
      other herbs (SI < 0.7). For example, four samples of Radix Codonopsis were of
      three distinct patterns (SI < 0.6). Our results highlight the situation that
      genetically distinct herbal materials are labeled and marketed under the same
      common names in an international market of Chinese medical herbs, which may
      contribute to inconsistency in quality and efficacy.

PMID- 14696681
TI  - Use of acupressure to improve gastrointestinal motility in women after trans
      abdominal hysterectomy.
AB  - The purpose of this study was to evaluate the effectiveness of acupressure on
      gastrointestinal (GI) motility in women after trans-abdominal hysterectomy (TAH).
      Patients were randomly assigned into two groups of 21 and 20 patients each. The
      experimental group received acupressure for 3 minutes at each of three meridian
      points: Neiguan (PC-6), Zusanli (ST-36) and Sanyinjiao (SP-6). The control group
      received 3 minutes of acupressure on sham points. Acupressure was performed twice
      a day. A questionnaire was used to determine patients' satisfaction prior to and
      after afternoon acupressure. GI contractions were measured with a multifunctional
      stethoscope before and after acupressure. Acupressure of these three meridian
      points significantly (p < 0.05) increased GI motility in the experimental group,
      but there was little change in the control group (p > 0.05). Our conclusions are
      that non-invasive acupressure of these meridian points can significantly improve
      GI motility and can be incorporated into the technical curriculum and clinical
      education program of nursing schools. Patients and their family members can be
      taught to continue this procedure at home to enhance GI motility in patients who
      have undergone TAH.

PMID- 14696682
TI  - The pain-relieving effects induced by electroacupuncture with different
      intensities at homotopic and heterotopic acupoints in humans.
AB  - The purpose of the present study was to investigate the relationship between the
      distribution of the analgesic area when different intensities of stimulation were
      applied to homotopic and heterotopic acupoints. The experiments were performed on
      volunteers; the left sural nerve was stimulated by a volley of eight rectangular
      pulses delivered at a frequency of 400 Hz. Electromyographic reflex responses
      (EMGs) were recorded from the ipsi-lateral biceps femoris muscle.
      Electroacupuncture stimuli were given on the skin overlying the Zusanli point (St
      36), and the strengths chosen were times of the threshold eliciting a nociceptive
      reflex (T(RIII)) response (0.6, 0.8, 1.0, T(RIII) and T(supra-RIII),
      respectively). The effects of homotopic and heterotopic stimuli applied to St 36
      on the pain sensation and the R(III), reflex elicited by stimulation of the left
      sural nerve were observed to explore the pain-relief and R(III) reflex-inhibition
      produced by stimulation of the St 36 point with different intensities. Both the
      nociceptive reflex and painful sensation evoked by stimulating the sural nerve
      were similarly inhibited by electroacupuncture at less than T(RIII) applied to
      the ipsi-lateral acupoint. In other words, acupuncture with an innocuous
      intensity can produce homotopic pain-alleviating effects and reflex suppression.
      With contra-lateral electroacupuncture at the St 36 acupoint, innocuous
      intensities cannot produce heterotopic pain-relieving effects; these inhibitions
      were only observed at electroacupuncture intensities similar to the T(RIII)
      threshold. These results suggest that local acupuncture-induced analgesia is
      effective with activation of large afferent fibers, whereas heterotopic
      acupuncture-induced analgesia is only effective with intensities strong enough to
      excite small afferent fibers. Local analgesic effects of acupoint stimulation
      involve segmental inhibition, whereas systemic analgesic effects of acupoint
      stimulation are involved in contra-lateral effects. The latter may recruit the
      diffuse noxious inhibitory controls (DNIC) system. The specific function of an
      acupoint is determined by the anatomical relationship between the disease focus
      and the segmental location of the acupoint.

PMID- 14696683
TI  - Acupuncture for acute torticollis: a pilot study.
AB  - The use of subjective end-points such as VAS pain scales in studies of
      acupuncture for chronic neck pain have resulted in equivocal results. This study
      introduces an objective parameter as the primary end-point for the assessment of
      acupuncture in patients with acute torticollis (stiff neck). Eighteen patients
      underwent a single 20-minute treatment session, with needling of two acupuncture
      points Hou Hsi (SI-3) and Luo Zhen (M-UE-24), on the side ipsilateral to the
      predominantly involved side of the neck. Measuring the angle of lateral head
      rotation using a simple compass and protractor, a mean improvement of 52.9% was
      found, more so among those presenting earlier (< 24 hours) as opposed to later (>
      72 hours; p = 0.034). The use of objective parameters, as seen in acupuncture
      research of the gastrointestinal and respiratory tracts, should be incorporated
      into studies of acute and chronic neck pain. The use of sham needle points and
      placebo needles is problematic since both may elicit physiological responses.

PMID- 14696684
TI  - Retrospective survey on therapeutic efficacy of Qigong in Korea.
AB  - Qigong is a complementary intervention for preventing and curing disease, and
      protecting and improving health through regulation of body and mind. Recently, we
      have been studying the psychoneuroimmunological effects of Qigong on the
      promotion of health. However, there are not many studies on the therapeutic
      efficacy of Qigong on various symptoms in Korea, hence the need to survey the
      clinical efficacy of Qigong. To evaluate the impact of Qigong in health care we
      categorized its effectiveness on the basis of ten years of subjects' memoranda.
      Among the 768 subjects, the motivation for doing Qigong was mostly to attend to
      health problems (81.5%), and males were more likely to use Qigong than females.
      The most improved symptoms were associated with psychological and musculoskeletal
      problems. Furthermore 66.9% of subjects reported improvements of perceived
      physical health and 40.3% of perceived psychological health. Other symptoms
      reduced by Qigong were pain (43.1%), fatigue (22.1%), and insomnia (8.7%). Wound
      healing was also surveyed (n = 332), and 84% of respondents reported improvement
      in recovery time, 66.6% reported reduced inflammation after Qigong and 50.3%
      reported no scarring as compared to before. In addition, 59.9% of respondents
      reported an increase in resistance to the common cold after four months of
      Qigong. The limitation of the study is that it is a retrospective survey on the
      basis of trainees' experiences of Qigong. Although this may constitute a
      potential bias, the study despite its limitations does provide precious empirical
      evidence of the effectiveness of Qigong.

PMID- 14696685
TI  - Using a health questionnaire to evaluate the effect of acupuncture treatment on
      non-specific clinical complaints.

PMID- 14696686
TI  - An aging India: perspectives, prospects, and policies.

PMID- 14696687
TI  - Demography of Indian aging, 2001-2051.
AB  - India is the second largest country in the world, with 72 million elderly persons
      above 60 years of age as of 2001, compared to China's 127 million. One of the
      objectives of this paper is to assess the emerging scenario of elderly for the
      first half of the 21st century. According to projections, the elderly in the age
      group 60 and above is expected to increase from 71 million in 2001 to 179 million
      in 2031, and further to 301 million in 2051; in the case of those 70 years and
      older, they are projected to increase from 27 million in 2001 to 132 million in
      2051. Among the elderly persons 80 and above, they are likely to improve their
      numbers from 5.4 million in 2021 to 32.0 million in 2051. The increasing number
      and proportion of elderly will have a direct impact on the demand for health
      services and pension and social security payments. Mobilizing resources for
      geriatric care and providing sufficient maintenance for the elderly will emerge
      as a major responsibility for heath-care providers and pension economists.

PMID- 14696688
TI  - Perspectives of research on aging in India.
AB  - Any social action plan, scheme, or program for welfare or intervention can be
      formulated only on the basis of data generated by research findings. Empirical
      data forms the backbone of the formulation of policy. This paper outlines the
      summary of the Indian research effort in the area of aging. An examination of the
      research trends shows both strengths and weaknesses. The generation of large and
      varied pieces of data across disciplines is a strength, while the absence of
      methodological rigor, integration of research effort, and the building of theory
      are the lacunae. The needs of the elderly, elder-care issues, State vs. family
      care, elder abuse, interventional and action plan research are some areas that
      need accentuation. Documentation of data, creation of databases, and a national
      body for overseeing research are requirements that cannot be delayed any longer.

PMID- 14696689
TI  - Economic security for the elderly in India: an overview.
AB  - The basic concept of social security is not new in India. Traditionally, a sort
      of moral economy existed to provide security to older destitute and other
      vulnerable groups in society. However, gradually, traditional support systems are
      disappearing, and state-based social security systems have come into existence.
      Under standardized economic security policies, government is covering retirement
      benefits for those in the organized sector; economic security benefits for those
      in the unorganized sector; and old-age pension for rural elderly. These are
      contributory as well as non-contributory programs. Besides life insurance
      approaches, savings-linked insurance and Annapurna (food security) are other
      important programs. However, in terms of coverage, program quality and
      effectiveness have been largely criticized by social security experts, suggesting
      immediate reforms to old-age programs.

PMID- 14696690
TI  - Health status and health care services among older persons in India.
AB  - India is characterized by significant rural-based living, population
      heterogeneity, financial constraints, and reverse sex ratio. Traditions of joint
      families, life-long physical activity, vegetarianism, and social and spiritual
      enrichment, all known to promote healthy aging, are widely prevalent. With the
      increasing pace of population aging, the health of older persons in India has
      been the focus of recent attention. Existing data indicate a significant
      morbidity among the aged, much of which may remain subclinical. Considerable
      variations in morbidity exist with respect to gender, place of residence (rural
      vs. urban), and socioeconomic status. Rapid demographic transition without a
      concomitant epidemiological transition is responsible for the dual load of
      infections and degenerative diseases in older persons, these being common causes
      of death. Most age-related morbidity is preventable. Health promotion and cost
      effective interventions based on the primary health care approach over a lifelong
      course, especially at the village level, will greatly help towards achieving the
      goal of healthy aging. The rapidly changing socioeconomic scenario in India also
      calls for appropriate policy actions to achieve this goal.

PMID- 14696691
TI  - Aging, disability, and disabled older people in India.
AB  - India is witnessing a demographic revolution, leading to a considerable increase
      in the proportion of older people in the population. Similarly, life expectancy
      of both the mentally and physically disabled has improved considerably. About 5%
      of Indian older people have problems with physical mobility. Aging has become a
      gender issue in India not only because more women are surviving into old age;
      they are also vulnerable and disadvantaged in many ways. In most cases they are
      the only caregivers available for the old and disabled. Older Indians are
      considered a high-risk group for multiple morbidity. It is estimated that nearly
      four million Indians suffer from mental problems. India has around 12 million
      people designated as "handicapped." However, little information is available
      about disabled people who grow older. The National Policy on Older Persons, which
      has been recently formulated, aims at providing an improved quality of life for
      millions of older Indians. However, the concerns of older disabled and of the
      disabled who grow old are still treated separately in both policy and practice.

PMID- 14696692
TI  - Social networks of old people in India: research and policy.
AB  - This article presents a comparative analysis of the available research on the
      social networks of older persons in India. Most of this research has been done in
      North Indian cities. The research foci of the available studies include network
      size, core networks and beyond, life course changes in networks, impacts of
      residency in old-age homes, gender differences, and joint and nuclear family
      residence. This research is discussed in terms of its policy implications.
      Because the research demonstrates that social networks are important for the
      welfare of older Indians, one can conclude that social policy that encourages the
      maintenance of robust networks throughout the life course may be worth pursuing.
      One aspect of policy is discussed. The analysis of the relationship between
      social network and gender suggests that current policies that can be seen as
      supporting gender inequality in terms of property may have a negative impact on
      the networks of older women.

PMID- 14696693
TI  - Issues of elder care and elder abuse in the Indian context.
AB  - With 7% of the population of India being elderly, two-thirds of whom live in
      villages and nearly a half of them in poor conditions, the care of the elderly is
      a difficult problem to be tackled. The dwindling of the joint family, the rise of
      dual-career families, a possible shift in filial piety values, the increasing
      life expectancy with greater chances of a prolonged old age characterized by
      poverty, degeneration, more empty-nest years, and dependency, have all added to
      the seriousness of the problem and made the elderly more susceptible than ever to
      abusive treatment. This paper examines these issues as well as the issue of elder
      abuse in light of available data and suggests some strategies to meet the
      problem. Also discussed are the problems, stresses, and strains of caregivers of
      the elderly. A greater role is envisaged for Non-Governmental Organizations
      (NGOs) than the state in the care of the elderly, particularly in providing
      support services to family caregivers.

PMID- 14696694
TI  - Geriatric hospitals in India, today and in the future.
AB  - In a country that shuns hospitalization of the elderly, regarding it as
      disrespect of those who helped youngsters evolve, Heritage Hospital (HH) is a
      welcome change, a model and pioneer stand-alone geriatric hospital. With its non
      ambulatory services looking after sick elderly, HH is like an extended family of
      seniors. HH's love and fresh air complement its Meals-on-Wheels program, guided
      by the nutritionist's healthy food. HH's Volunteer Guild; its Diabetes Club, ever
      growing with India's dramatic rise in the number of diabetics; its Senior Net
      Club's Click@50, making elders computer savvy; and Grandparent-Grandchild and
      Golden and Silver Couple contests celebrated on October 1st, are all widely
      appreciated, enforcing strong values Indians still share on marriage and family.
      Heritage brings together 10,000 seniors in Hyderabad, strengthening its motto of
      Eastern philosophy with its strong emphasis on care for the elderly.

PMID- 14696695
TI  - Old-age homes and services: old and new approaches to aged care.
AB  - Although generational co-residence continues to be the dominant form of housing
      and care for Indian elders and only 1% live in old-age homes, the numbers and
      types of these homes are growing. This article describes a recent study of 48 old
      age homes in different parts of India, approximately 12%-15% of all homes. They
      included the more traditional free homes for the aged poor who have no family to
      care for them and the more recent for-pay homes for the middle-class. A small
      number of day-care centers, also a new phenomenon, were investigated. Two- to
      three-hour structured interviews were conducted with managers, supervisors, and
      trustees, augmented by a checklist of environmental and neighborhood features.
      Most homes house small numbers of residents, have common spaces for dining, TV
      and prayer, have access to medical care and transportation, provide meals and
      some assistance with activities of daily living, and are open to all castes. All
      are run by non-governmental organizations (NGOs), only one-third with any
      government assistance. Free homes tend to be bigger and older, serve nonaged
      clients, have less privacy and emphasize occupational therapy and income
      generating activities, and are more like board-and-care homes. For-pay homes have
      more privacy and western-style amenities, focus on local community outreach and
      provide fewer meals. The gradual increase of all old-age homes has given rise to
      debates about their appropriate roles in Indian society and about their quality.
      Government grants to NGOs for homes and day-care centers (often considered more
      appropriate support for elders) are limited. With the National Policy on Older
      Persons looking to NGOs and village councils to be the primary sources of non
      familial aged care, several ways to build their capacity are suggested.

PMID- 14696696
TI  - The role of non-governmental organizations for the welfare of the elderly: the
      case of HelpAge India.
AB  - Since there has been a gradual increase in the population aged 60 and older, a
      developing country like India is unable to cope with the needs and problems of
      its aged populations. While the government continues its efforts to introduce
      programs for the elderly, the non-governmental organizations (NGOs) have played a
      key role in bringing to the forefront the socioeconomic and health problems of
      older people in the society at large. This paper looks at the role of the NGOs
      through their various welfare activities and beneficial programs in carving out a
      place for the elderly in India. The work of HelpAge India is highlighted to
      examine how voluntary organizations have worked in the field of aging in India
      and made an impact on the lives of the senior citizens, especially those below
      the poverty line who are economically and socially deprived.

PMID- 14696697
TI  - Senior grassroots organizations in India.
AB  - Organizations for the elderly at the grassroots level began to function in India
      from the third decade of the 20th century. They belong to two major types:
      Pensioners' Associations (PAs) and Senior Citizens' Associations (SCAs). PAs
      claim a membership of approximately 13 million and are structured and vertically
      organized. The SCAs are loosely organized and most are unitary. They have
      together a membership of less than 5 million. Programs of PAs are mainly confined
      to members; those of SCAs are wider but mainly urban-biased and middle-class
      oriented. Neither of them is powerful in lobbying. Of late, Government of India's
      (GOI) policy on the elderly (NPOP, 2000) has given a fillip to the SCAs which are
      gathering strength, and some, at least, are vying for availing GOI program
      benefits.

PMID- 14696698
TI  - Towards a policy for aging in India.
AB  - India has been engaged in developing the National Policy for elderly for the last
      two decades. The efforts to establish a policy began building on traditional
      values, a small number of pre-independence enactments. Lawgivers of India spoke
      of the rights of the elderly and the responsibility of the state towards them
      almost 2000 years ago. Additional factors such as culture, social norms, and
      influence of international organizations, particularly the Vienna Plan of Action,
      have been responsible for shaping the Policy. The Plan of Action agreed upon at
      the end of the Vienna meeting could not come into being due to several reasons
      such as the size of the country and its federal structure. This article takes an
      overview of the efforts made by the federal government and the NGOs to create a
      National Policy. The article describes the process by which the National Policy
      came into being and provides an overview and critique of the present Policy. The
      author makes a summary of the major areas of action suggested by the Policy, the
      strategies designed, and the implementation roles of different Ministries. The
      author describes the steps taken since 1999 and provides the concluding remarks.

PMID- 14696699
TI  - Sex in Australia: a guide for readers.
AB  - The Australian Study of Health and Relationships (ASHR), a survey of 19,307
      people aged 16-59 years which had a broad focus across many aspects of sexual and
      reproductive health. Our primary goal in presenting these data is to describe the
      overall prevalence of key outcomes and the ways in which they are patterned with
      respect to a range of sociodemographic factors. The socio-demographic factors
      used include age, gender, language spoken at home, highest level of education
      completed, region of residence, household income and occupational category. Where
      appropriate we also include stated sexual identity. Our choice of these factors
      reflects the fact that they are major elements in the structure of the Australian
      population and Australian society. For the purpose of reporting the initial
      results, we have grouped these outcomes into 18 papers. They are bracketed by an
      introductory methods paper which provides a detailed account of the design and
      execution of the study, and a concluding paper reflecting on the key themes
      emerging from the findings, the strengths and limitations of our approach and
      recommendations for future research.

PMID- 14696700
TI  - Sex in Australia: the rationale and methods of the Australian Study of Health and
      Relationships.
AB  - OBJECTIVE: To describe the methods and process of the Australian Study of Health
      and Relationships. METHODS: A computer-assisted telephone interview was developed
      and applied to a stratified sample of the Australian population. After initially
      weighting to reflect the study design, the sample was further weighted to reflect
      the location, age and sex distribution of the 2001 Census. RESULTS: Interviews
      were completed with 10,173 men and 9,134 women aged 16-59 years from all states
      and Territories. The overall response rate was 73.1% (69.4% among men and 77.6%
      among women). After accounting for the survey design and weighting to the 2001
      Census, the sample appears broadly representative of the Australian population.
      CONCLUSION: The combination of methods and design in the Australian Study of
      Health and Relationships, coupled with the high response rate, strongly suggests
      that the results of the study are robust and broadly representative of the
      Australian population.

PMID- 14696701
TI  - Sex in Australia: attitudes towards sex in a representative sample of adults.
AB  - OBJECTIVE: To describe social attitudes towards sex of Australian adults and
      correlates of a scale of sexual liberalism. METHODS: Computer-assisted telephone
      interviews were completed by a representative sample of 10,173 men and 9,134
      women aged 16-59 years. The overall response rate was 73.1% (69.4% men, 77.6%
      women). Respondents were asked about their agreement with nine attitude
      statements. Factor analysis and examination of internal consistency resulted in a
      six-item scale of liberalism. Correlates of attitude statements and the
      liberalism scale were examined. RESULTS: Most people agreed that premarital sex
      was acceptable, that oral sex was considered 'sex', that sex was important for a
      sense of well-being and that extramarital sex was unacceptable. Men were more
      likely (36.9%) to disapprove of sex between two men than women were to disapprove
      of sex between two women (25.1%). Higher levels of education were associated with
      increased liberalism for men and women, as was speaking English at home,
      identifying as homosexual or bisexual, vaginal intercourse before age 16, having
      had more than one sexual partner in the year before interview, having had
      heterosexual anal intercourse, having no religion or faith, smoking tobacco, and
      drinking more alcohol. CONCLUSION: Sexual attitudes of Australians largely
      support a heterosexual paradigm with no sex outside the relationship. High levels
      of approval of premarital sex are consistent with decreasing age of first
      intercourse in Australia. Higher levels of liberalism were associated with
      greater sexual adventurism and health risk taking.

PMID- 14696702
TI  - Sex in Australia: selected characteristics of regular sexual relationships.
AB  - OBJECTIVE: To describe selected characteristics of Australian adults' regular or
      ongoing sexual relationships. METHOD: Computer-assisted telephone interviews were
      completed by a representative sample of 10,173 men and 9,134 women aged 16-59
      years. The overall response rate was 73.1% (69.4% men, 77.6% women). Respondents
      indicated how often they had sex in the past four weeks, contraceptive use, their
      own and their partners' expectations about having sex with other people during
      their relationship, whether they had discussed these expectations with their
      partners and whether they had an explicit agreement about sex with other people.
      RESULTS: 85.3% of men and 89.5% of women were in a regular heterosexual
      relationship, among whom 81.4% of men and 89.3% of women reported contraceptive
      use. Men and women who had a regular partner for the past 12 months had had sex
      with their partners an average of 1.84 times per week in the four weeks before
      interview; younger people had sex more often. Most respondents expected
      themselves and their partners to not have sex with other people, although men
      were less likely than women to have discussed these expectations with their
      partner. Bisexually identified men and women were significantly less likely than
      heterosexually identified men and women to support having sex only with their
      regular partner. Only 4.9% of men and 2.9% of women in regular heterosexual
      relationships had concurrent sexual partners in the past 12 months. CONCLUSION:
      Australians' attitudes to not having sex with people while in a regular
      relationship are highly consistent with their behaviour.

PMID- 14696703
TI  - Sex in Australia: first experiences of vaginal intercourse and oral sex among a
      representative sample of adults.
AB  - OBJECTIVE: To describe the characteristics of Australian adults' first vaginal
      intercourse and contraceptive use on that occasion, as well as first oral sex.
      METHOD: Computer-assisted telephone interviews were completed by a representative
      sample of 10,173 men and 9,134 women aged 16-59 years. The overall response rate
      was 73.1% (69.4% men, 77.6% women). Respondents indicated their age at first
      vaginal intercourse (if ever), the partner's age, their relationship to their
      partner, the duration of the relationship before first intercourse, and what
      contraception (if any) was used. Respondents also indicated their age when they
      first had oral sex. RESULTS: For men, the median age at first intercourse
      declined from 18 among men aged 50-59 to 16 for men aged 16-19. For women the
      decline in median age was from 19 to 16. For women born between 1941 and 1950 the
      difference in median age at first vaginal intercourse and subsequent first oral
      sex was six years but for women born between 1981 and 1986 the difference in
      medians was one year. For men, a similar convergence was observed. Contraceptive
      use at first intercourse has increased significantly, from less than 30% of men
      and women in the 1950s to over 90% in the 2000s. For men, first intercourse
      before age 16 was significantly associated with greater numbers of lifetime and
      recent sexual partners, ever having paid for sex and having had a sexually
      transmitted infection (STI), and for women, with greater numbers of lifetime and
      recent sexual partners, ever having been paid for sex and ever having had an STI.
      CONCLUSION: Sex education should be given so that all young people have
      information about contraception and disease prevention before they begin their
      sexual careers.

PMID- 14696704
TI  - Sex in Australia: sexual identity, sexual attraction and sexual experience among
      a representative sample of adults.
AB  - OBJECTIVE: To describe the prevalence of same-sex and opposite-sex attraction and
      experience in Australia and the prevalence of different sexual identities.
      METHOD: Computer-assisted telephone interviews were completed by a representative
      sample of 10,173 men and 9,134 women aged 16-59 years from all States and
      Territories of Australia. The overall response rate was 73.1% (men, 69.4%; women,
      77.6%). Men and women were asked about their experience of same-sex and opposite
      sex attraction and experience along with their sexual identity. The agreement and
      disagreement between sexual attraction and sexual experience were explored.
      RESULTS: Among men, 97.4% identified as heterosexual, 1.6% as gay or homosexual
      and 0.9% as bisexual. Among women, 97.7% identified as heterosexual, 0.8% as
      lesbian or homosexual and 1.4% as bisexual. Among men, 91.4% reported only
      opposite-sex attraction and experience, as did 84.9% of women. Thus, some same
      sex attraction or experience was reported by 8.60% of men and 15.1% of women. Of
      men, 4.2% reported sexual attraction and sexual experience that was inconsistent,
      as did 8.2% of women. Factors associated with this agreement or disagreement
      included age group, non-English-speaking background, education and socio-economic
      status. CONCLUSION: Relatively few Australians reported a sexual identity other
      than heterosexual. However, both same-sex attraction and homosexual experience
      are more common than homosexual or bisexual identity would suggest. Reporting
      same-sex attraction or experience was associated with poorer mental health and is
      likely to reflect responses to homophobia in Australian society.

PMID- 14696705
TI  - Sex in Australia: heterosexual experience and recent heterosexual encounters
      among a representative sample of adults.
AB  - OBJECTIVE: To describe numbers of opposite-sex partners, experiences of different
      heterosexual behaviours, and recent heterosexual experiences among a
      representative sample of Australian adults. METHODS: Computer-assisted telephone
      interviews were completed by a representative sample of 10,173 men and 9,134
      women aged 16-59 years from all States and Territories. The response rate was
      73.1% (69.4% among men and 77.6% among women). RESULTS: Men reported more sexual
      partners than women over their lifetime, in the past five years and in the past
      year. 15.1% of men and 8.5% of women reported multiple sexual partners in the
      past year. Reporting multiple opposite-sex partners was significantly associated
      with being younger, identifying as bisexual, living in major cities, having a
      lower income, having a blue-collar occupation, and not being married. All but a
      handful of respondents' most recent heterosexual encounters involved vaginal
      intercourse and condoms were used in one-fifth of these sexual encounters. Anal
      intercourse was very uncommon during respondents' most recent heterosexual
      encounters. CONCLUSION: Patterns of heterosexual experience in Australia are
      similar to those found in studies of representative samples in other countries.
      IMPLICATIONS: There may be a need for interventions targeted at people with
      multiple sexual partners to promote safer sexual behaviour and to reduce the
      likelihood of transmission of HIV and other sexually transmitted infections.

PMID- 14696706
TI  - Sex in Australia: homosexual experience and recent homosexual encounters.
AB  - OBJECTIVE: To describe the prevalence and features of homosexual experience and
      recent homosexual encounters among a representative sample of Australian adults.
      METHODS: Computer-assisted telephone interviews were completed by a
      representative sample of 10,173 men and 9,134 women aged 16-59 years from all
      States and Territories. The overall response rate was 73.1% (69.4% among men and
      77.6% among women). RESULTS: Overall, 8.6% of women and 5.9% of men reported some
      homosexual sexual experience in their lives (p<0.001); these figures fell to 5.7%
      and 5.0% respectively (p=0.106) when non-genital sexual experience was excluded.
      1.9% of men and 1.5% of women reported homosexual experience in the past year.
      Men who reported homosexual experience reported more same-sex partners than did
      women (means 31.6 and 3.2, p<0.001), and men and women who identified as
      homosexual or bisexual reported more sexual partners in total than those who
      identified as heterosexual. Respondents reporting homosexual experience were
      significantly more likely to be from an English-speaking background, have higher
      levels of education, live in a major city, and report a white-collar or
      managerial/professional occupation. Women who reported homosexual experience were
      less likely to have a middle or high income. In the most recent homosexual
      encounter, genital touching was the most commonly reported practice, and oral sex
      was reported much more frequently than in heterosexual encounters. CONCLUSION:
      Homosexually and bisexually identified men and women had higher total numbers of
      partners than heterosexuals. Improved societal attitudes towards homosexuality
      are likely to lead to further increases in estimates of the prevalence of
      homosexual experience in the community.

PMID- 14696708
TI  - Sex in Australia: sexual and emotional satisfaction in regular relationships and
      preferred frequency of sex among a representative sample of adults.
AB  - OBJECTIVES: To document sexual and emotional satisfaction with their
      relationships and desired and actual frequency of sex among a representative
      sample of Australian adults. METHOD: Between mid-2001 and mid-2002, computer
      assisted telephone interviews were completed by 10,173 men and 9,134 women aged
      16-59 years from all States and Territories selected by modified random-digit
      dialling of households (response rate 73.1%). Respondents in a regular
      relationship were asked how physically pleasurable they found sex with the
      partner to be and how emotionally satisfying the relationship was. All
      respondents were asked how often they would ideally like to have sex and how
      often they had sex in the past four weeks. RESULTS: Most people in heterosexual
      relationships found sex very or extremely pleasurable (90.3% men, 79.1% women)
      and the relationship emotionally satisfying (87.5% men, 79.2% women); men were
      more satisfied with both. Physical pleasure in sex was correlated with emotional
      satisfaction. One person in four had had no sex in the past four weeks; most
      people had had sex less than twice a week. Most people wanted ideally to have sex
      more often than they did. However, 24.3% of men but only 8.3% of women said they
      ideally wanted sex daily or more often. CONCLUSION: Men on average express higher
      levels of relationship satisfaction and of sexual interest, but the overlap
      between men and women is large.

PMID- 14696707
TI  - Sex in Australia: sexual difficulties in a representative sample of adults.
AB  - OBJECTIVES: The Australian Study of Health and Relationships reports on sexual
      behaviours in a representative sample of Australian adults. METHOD: Between May
      2000 and June 2001, computer-assisted telephone interviews were completed by a
      representative sample of 10,173 men and 9,134 women aged 16 to 59 years (response
      rate 73.1%). Respondents were asked whether in the past year they had for a
      period of at least one month experienced a range of sexual difficulties. RESULTS:
      The most common sexual difficulty was lack of interest in having sex (24.9% men,
      54.8% women). Women were more likely than men to report being unable to come to
      orgasm (28.6% vs. 6.3%), not finding sex pleasurable (27.3% vs. 5.6%), physical
      pain during intercourse (20.3% vs. 2.4%) or worrying during sex about their body
      looking unattractive (35.9% vs. 14.2%). Men were more likely to report coming to
      orgasm too quickly (23.8% vs. 11.7%). Men (16.0%) and women (17.0%) were equally
      likely to have felt anxious about their ability to perform sexually. Erectile
      difficulties and lack of interest in sex were higher among the over-40s. Anxiety
      about performance was highest among men under 20. Experience of sexual
      difficulties correlated with self-reported ill health. CONCLUSION: The assumption
      that everyone should be interested in sex, should want to have it and should
      enjoy having it is a socially normative prescription and not a description of the
      actual state of affairs. Women reported less interest in sex, less pleasure and
      more pain than men.

PMID- 14696709
TI  - Sex in Australia: autoerotic, esoteric and other sexual practices engaged in by a
      representative sample of adults.
AB  - OBJECTIVES: To describe the prevalence of a range of autoerotic and other non
      coital sexual practices among Australians. METHOD: Computer-assisted telephone
      interviews were completed by a representative sample of 10,173 men and 9,134
      women aged 16-59 years (response rate 73.1%). Respondents were asked whether in
      the past year they had: masturbated, engaged in various other autoerotic
      activities, or engaged in any of six other non-coital or esoteric practices.
      RESULTS: Half of the respondents (65% men, 35% women) had masturbated in the past
      year. Nearly half (48%) of the men and 25% of the women had masturbated in the
      past four weeks, among whom men had done so a mean of 5.8 times and women 3.3
      times. About a quarter of all respondents had watched an X-rated film (37% men,
      16% women), 12% of men and 14% of women had used a sex toy, and 17% of men and 2%
      of women had visited an Internet sex site. 17% of men and 14% of women had
      engaged in digital-anal stimulation with a partner. Phone sex, role play or
      dressing up, bondage and discipline, sadomasochism or dominance and submission
      (BDSM-DS), fisting (rectal or vaginal, insertive or receptive) and rimming (oral
      anal stimulation) were all engaged in by less than 5% of the sample. CONCLUSION:
      Most of the practices studied were engaged in by more men than women. A range of
      autoerotic activities are both substitutes for partnered sex and additional
      sources of pleasure for people with sexual partners.

PMID- 14696710
TI  - Sex in Australia: experiences of commercial sex in a representative sample of
      adults.
AB  - OBJECTIVE: To describe the characteristics of Australian adults' experience of
      commercial sex. METHOD: Telephone interviews were completed by a representative
      sample of 10,173 men and 9,134 women aged 16-59 years (response rate 73.1%; 69.4%
      men, 77.6% women). Respondents were asked about their experiences both as clients
      and as sex workers. Socio-demographic and health factors associated with
      experience of commercial sex were explored for men. RESULTS: Almost one in six
      Australian men (15.6%) have ever paid for sex; 1.9% had done so in the past year.
      Of men who had ever paid for sex, 97% had paid for sex with a woman and 3% for
      sex with a man. Very few women (0.1%) had ever paid for sex. Twice as many men
      (0.9%) as women (0.5%) had ever been paid for sex; two-thirds of these men (0.6%)
      were paid by other men. Condom use during vaginal sex was highest in parlours and
      brothels and with escorts, and lowest for street sex work. Two-thirds of women
      who had ever been paid for sex had done so only overseas. One in 10 men who had
      paid for sex had only done so overseas. Men who had paid for sex were more likely
      than other men to smoke, to drink more alcohol, to have had a sexually
      transmitted infection or been tested for HIV, to have more sexual partners, to
      have first had vaginal intercourse before 16, and to have had heterosexual anal
      intercourse. CONCLUSION: Sex work overseas, where condom use may not be common,
      represents a potential source of HIV or sexually transmitted infection.

PMID- 14696711
TI  - Sex in Australia: experiences of sexual coercion among a representative sample of
      adults.
AB  - OBJECTIVE: To provide reliable estimates of the prevalence, correlates and
      consequences of sexual coercion among a representative sample of Australian
      adults. METHODS: Computer-assisted telephone interviews were completed by a
      representative sample of 10,173 men and 9,134 women aged 16-59 years. The
      response rate was 73.1% (69.4% men, 77.6% women). RESULTS: Overall, 4.8% of men
      and 21.1% of women had experienced sexual coercion, i.e. being forced or
      frightened into unwanted sexual activity, and 2.8% of men and 10.3% of women had
      been coerced when aged 16 or younger. Although women were significantly more
      likely than men to have been sexually coerced, correlates of sexual coercion were
      similar for men and women and were not limited to effects on sexual behaviour.
      People who had been coerced reported greater psychosocial distress, were more
      likely to smoke, were more anxious about sex, and more likely to have acquired a
      sexually transmitted infection. Few people had talked to others about their
      experiences of sexual coercion and fewer had talked to a professional.
      CONCLUSION: Sexual coercion is an unacceptably common experience. Sexual coercion
      has detrimental effects on various aspects of people's lives. It most commonly
      occurs at the ages at which people become sexually active and women are more
      likely than men to be sexually coerced. IMPLICATIONS: There may be need for more
      readily accessible services that are better able to minimise the detrimental
      effects of sexual coercion. This is in addition to a more general need to reduce
      the incidence of sexual coercion.

PMID- 14696712
TI  - Sex in Australia: reproductive experiences and reproductive health among a
      representative sample of women.
AB  - OBJECTIVE: To document the reproductive experiences of a representative sample of
      Australian women aged 16-59 years. METHOD: Computer-assisted telephone interviews
      were completed by a representative sample of 10,173 men and 9,134 women aged 16
      59 years from all States and Territories. The overall response rate was 73.1%
      (69.4% among men, and 77.6% among women). Women were asked the number of times
      they had experienced a live birth, a still birth, a miscarriage and a termination
      of pregnancy. RESULTS: Of the women surveyed, 15.5% reported having experienced
      difficulty in becoming pregnant and 76.1% had been pregnant at least once. Nearly
      all the women who had been pregnant reported experiencing a live birth.
      Substantial minorities of women reported having experienced a miscarriage (33.4%)
      or a termination of pregnancy (22.6%). The percentage of women who reported
      becoming pregnant the first time as a teenager declined from 22.8% among women
      aged 50-59 to 16.9% among women aged 20-29. Of those who had had vaginal
      intercourse, 19.2% had used emergency contraception, 53.3% of them only once.
      CONCLUSION: There was clear evidence of substantial changes in the fertility of
      Australian women over the past 40 years.

PMID- 14696713
TI  - Sex in Australia: contraceptive practices among a representative sample of women.
AB  - OBJECTIVES: To document the use of contraception by a representative sample of
      Australian women aged 16-59 years. METHOD: Between mid-2001 and mid-2002,
      computer-assisted telephone interviews were completed by 9,134 women aged 16-59
      years from all States and Territories selected by modified random-digit dialling
      of households (response rate 77.6%). Respondents were asked about contraceptive
      methods used in their current regular relationship(s) and during recent sexual
      encounters, or in general, or their reasons for non-use. Responses were allocated
      to 14 categories. RESULTS: 70.8% of respondents were using a method of
      contraception, over 95% of those apparently at risk of pregnancy. Most common
      reasons for non-use were not having intercourse (41.6%) and being past menopause
      (21.6%). Among those apparently at risk of unplanned pregnancy (i.e. who were
      heterosexually active and fertile but not pregnant or trying to become pregnant;
      13.0% of non-users), the most common reasons for non-use were experience of side
      effects or contra-indications (23.0%), leaving it to chance (20.2%),
      forgetting/not caring (18.9%), breast feeding (16.5%) and believing it
      unnatural/unhealthy (13.7%). No women cited religious objections or lack of
      access to services. The most used methods were oral contraceptives (33.6% of
      users), tubal ligation/hysterectomy (22.5%), condom (21.4%) and vasectomy of
      partner (19.3%). Tubal ligation rates were higher and condom use lower in
      regional and remote areas. CONCLUSION: Given the high levels of use and knowledge
      and lack of evidence of unmet service need, most unplanned pregnancies in
      Australian adults are likely to be attributable to method failure or inconsistent
      use.

PMID- 14696714
TI  - Sex in Australia: experience of condom failure among a representative sample of
      men.
AB  - OBJECTIVE: Condom use is a central part of strategies to prevent the transmission
      of human immunodeficiency virus and other sexually transmissible infections. The
      objective of this study was to provide reliable estimates of the prevalence and
      correlates of condom failure among a representative sample of Australian men.
      METHODS: Computer-assisted telephone interviews were completed by a
      representative sample of 10,173 men aged 16-59 years from all States and
      Territories. The response rate was 69.4%. RESULTS: Among men who used condoms in
      the year prior to being interviewed, 23.8% experienced at least one condom
      breakage in the past year and 18.1% experienced at least one condom slippage in
      the past year. Experience of condom breakage in the past year was significantly
      related to younger age, having a blue-collar occupation, and using more condoms.
      Neither condom slippage nor condom failure was significantly related to use of
      water-based lubricants or oil-based lubricants. CONCLUSION: Condom failure is
      related to certain characteristics of individuals and is not randomly distributed
      across all condom users. Lubricant use did not affect condom failure.
      IMPLICATIONS: There may not be a need to promote lubricant use for vaginal
      intercourse, as there was no association between lubricant use and condom
      failure.

PMID- 14696715
TI  - Sex in Australia: safer sex and condom use among a representative sample of
      adults.
AB  - OBJECTIVE: To provide reliable estimates of the frequency of condom use and
      correlates of condom use among Australian adults. METHODS: Computer-assisted
      telephone interviews were completed by a representative sample of 10,173 men and
      9,134 women aged 16-59 years. The response rate was 73.1% (69.4% men, 77.6%
      women). RESULTS: Although the majority of respondents had used a condom at some
      time in their lives, fewer than half of the respondents who were sexually active
      in the year before being interviewed had used a condom in the past year. Condom
      use in the past year was associated with youth, greater education, residence in
      major cities, lower incomes, white-collar occupations, being a former smoker, and
      having more sexual partners in the past year. In the six months prior to
      interview, 7.1% of respondents always used condoms with regular cohabiting
      partners, 22.5% always used condoms with regular non-cohabiting partners, and
      41.4% always used condoms with casual partners. Approximately 20% of respondents
      used a condom the last time they had vaginal intercourse, and one in eight of
      these condoms were put on after genital contact. Condom use during the most
      recent sexual encounter was associated with youth, living in a major city, having
      a lower income, having sex with a casual partner, and not using another form of
      contraception. CONCLUSION: As in other studies, condom use was strongly
      associated with partner type and use of other contraception. IMPLICATIONS: People
      with multiple sexual partners need to be aware that non-barrier methods of
      contraception (and condoms applied late) do not protect against sexually
      transmitted infections.

PMID- 14696716
TI  - Sex in Australia: knowledge about sexually transmissible infections and blood
      borne viruses in a representative sample of adults.
AB  - OBJECTIVE: To describe knowledge related to sexually transmitted infection (STI)
      and blood-borne virus (BBV) infection in a representative sample of Australian
      adults. METHODS: Computer-assisted telephone interviews were completed by a
      representative sample of 10,173 men and 9,134 women aged 16-59 years from all
      States and Territories. The overall response rate was 73.1% (69.4% among men and
      77.6% among women). Respondents were read a series of statements about STIs and
      BBVs and asked to say if they believed they were true or false. Predictors of
      knowledge were examined. RESULTS: Respondents were more likely to answer
      correctly questions about hepatitis C than questions about herpes, gonorrhoea,
      genital warts and chlamydia. Women had better knowledge than men. Other
      predictors of better knowledge included speaking English at home, homosexual or
      bisexual identity, higher educational levels, higher income, higher occupational
      level and a previous STI diagnosis. CONCLUSION: Knowledge of transmission routes
      and health consequences of the most common STIs was poor. Although knowledge is
      only one prerequisite for effective disease prevention, the findings suggest that
      improving public knowledge of STIs is an urgent task in reducing the morbidity
      associated with these common infections. IMPLICATIONS: Education campaigns to
      increase knowledge of the transmission and health consequences of STIs are
      urgently required if the substantial morbidity associated with these common
      infections is to be reduced.

PMID- 14696717
TI  - Sex in Australia: sexually transmissible infection and blood-borne virus history
      in a representative sample of adults.
AB  - OBJECTIVE: To describe the lifetime and recent history of STIs and BBV, including
      place of seeking treatment, in a representative sample of Australian adults.
      METHODS: Computer-assisted telephone interviews were completed by a
      representative sample of 10,173 men and 9,134 women aged 16-59 years from all
      States and Territories. The overall response rate was 73.1% (69.4% among men and
      77.6% among women). RESULTS: Overall, 20.2% of men and 16.9% of women had ever
      been diagnosed with an STI or BBV, and 2.0% and 2.2% respectively had been
      diagnosed in the past year. The participant's usual general practitioner was the
      most common location of treatment. Sexual health clinics accounted for a small
      proportion of treatment locations. Predictors of recent STI or BBV diagnosis in
      men included homosexual or bisexual identity, a history of sex work as a worker
      or client, a history of injecting drugs and having more than one partner in the
      past year. In women, predictors included bisexual identity, history of sex work
      as a worker, injecting drug use, and having more than one partner in the past
      year. Around 40% of men and women had been tested for HIV and in homosexually
      identified men, 77% had been tested. CONCLUSION: STIs and BBVs are common
      infections in Australia and care is mostly received from general practitioners.
      Although a variety of predictors, including homosexual or bisexual identity,
      injecting drug use and sex work were related to STI diagnosis, STIs were not
      uncommon among people without these risk factors. IMPLICATIONS: General
      practitioners in Australia require a high level of expertise to recognise, offer
      testing, and manage common STIs and BBVs.

PMID- 14696718
TI  - Sex in Australia: injecting and sexual risk behaviour in a representative sample
      of adults.
AB  - OBJECTIVE: Some blood-borne and sexually transmissible agents may be spread by
      using non-sterile injecting equipment and by unprotected sexual intercourse. The
      objective of this study was to describe the prevalence of these risk factors in
      the general population of Australia. METHODS: Computer-assisted telephone
      interviews were completed by a representative sample of 10,173 men and 9,134
      women aged 16-59 years. The overall response rate was 73.1% (69.4% men, 77.6%
      women). RESULTS: 3% of respondents had ever injected non-prescription drugs; men
      were more likely than women to have done so. Predictors of injecting in men and
      women included being aged 20-29, homosexual or bisexual identity, and lower
      levels of education and income. Injecting was not more common in cities than
      elsewhere. Among people who had injected in the past year, 12.4% had shared
      needles and 43.0% had shared other paraphernalia. Sharing was significantly
      related to lower income. Unprotected sex with casual partners was more common in
      heterosexual activity than in male homosexual activity. Among heterosexually
      active respondents, 3.3% reported unprotected vaginal sex with casual partners
      (59% of those with such partners) and among homosexually active males 2.1%
      reported unprotected anal sex with casual partners (12% of those with such
      partners). Predictors of unprotected sex included indices of lower socio-economic
      status. CONCLUSION: Sexual and injecting risks are reported by substantial
      minorities of the Australian population and are associated with indices of lower
      socio-economic status and bisexual identity. Programs are needed to address
      vulnerabilities to these infections.

PMID- 14696719
TI  - Sex in Australia: reflections and recommendations for future research.
AB  - OBJECTIVE: To review the content, method and process of the Australian Study of
      Health and Relationships (ASHR). RESULTS: ASHR achieved a large sample, a high
      response rate and documented the sexual life histories and current sexual health
      related knowledge, attitudes and practices of the Australian population aged 16
      59. Its cross-sectional nature limited our ability to partition observed
      variation between age and time despite clear evidence of both age-related and
      cohort-related changes in sexual practice. Similarly, its reliance on a sample of
      individuals reporting on their sexual experiences rather than a sample of sexual
      relationships or encounters and their participants limits our ability to
      understand the dynamics of those relationships and encounters. Finally, our
      understanding of sexuality in Australia could have been improved through
      qualitative studies with a subsample of ASHR participants. CONCLUSION: ASHR
      represents a significant contribution to our understanding of sexual health
      related knowledge, attitudes and practices in Australia.

PMID- 14696720
TI  - Affective neuroscience and psychophysiology: toward a synthesis.
AB  - This article reviews the author's program of research on the neural substrates of
      emotion and affective style and their behavioral and peripheral biological
      correlates. Two core dimensions along which affect is organized are approach and
      withdrawal. Some of the key circuitry underlying approach and withdrawal
      components of emotion is reviewed with an emphasis on the role played by
      different sectors of the prefrontal cortex (PFC) and amygdala. Affective style
      refers to individual differences in valence-specific features of emotional
      reactivity and regulation. The different parameters of affective style can be
      objectively measured using specific laboratory probes. Relations between
      individual differences in prefrontal and amygdala function and specific
      components of affective style are illustrated. The final section of the article
      concludes with a brief discussion of plasticity in the central circuitry of
      emotion and the possibility that this circuitry can be shaped by training
      experiences that might potentially promote a more resilient, positive affective
      style. The implications of this body of work for a broader conception of
      psychophysiology and for training the next generation of psychophysiologists are
      considered in the conclusion.

PMID- 14696721
TI  - Mental rotation delays the heart beat: probing the central processing bottleneck.
AB  - We tested the hypothesis that mental rotation would delay response-related
      processing as indicated by transient slowing of the heart beat. Thirty college
      age subjects (half female) were presented with normal and mirror image letters
      rotated at 0, 60, 120, and 180 degrees. Three letters were assigned to a right
      hand response; a separate three to a left-hand response. Responses were only
      required for letters in one orientation, mirror or normal. Continuous measures of
      interbeat interval (IBI) of the heart, respiration, and muscle tension were
      collected. Performance results were largely consistent with prior findings.
      Greater angular displacement of the stimuli was associated with greater
      lengthening of IBI immediately after the stimulus. IBI was influenced equally by
      angle of rotation in respond and inhibit trials. The lengthening of IBI was
      interpreted as due to a delay in response selection and execution due to mental
      rotation.

PMID- 14696722
TI  - Correspondence between laboratory and ambulatory measures of cardiovascular
      reactivity: a multilevel modeling approach.
AB  - We examined the correspondence between laboratory measures of cardiovascular
      reactivity (CVR) and within-person changes in cardiovascular activity during the
      challenges of daily life, after adjustment for posture, activity, and other
      effects. Healthy adults (n = 335) were administered laboratory measures of CVR
      along with 6 days of ambulatory blood pressure monitoring and electronic diary
      reports. Compared with low reactors, high laboratory systolic blood pressure
      (SBP) reactors showed larger increases in SBP during periods of high task demand
      or low decisional control in daily life. High diastolic blood pressure (DBP)
      reactors showed larger increases in ambulatory DBP during situations rated as
      both low control and high demand. This multilevel modeling approach may enhance
      our ability to detect the correspondence between laboratory and ambulatory
      measures of CVR, and to identify the circumstances under which it may be most
      clearly observed.

PMID- 14696723
TI  - Meta-analysis of P300 and schizophrenia: patients, paradigms, and practical
      implications.
AB  - The goal of the present meta-analysis was to identify factors that contribute to
      P300 event-related brain potential (ERP) differences in patients with
      schizophrenia compared to unaffected controls in an attempt to characterize the
      clinically relevant dimensions underlying P300 deficits in patients with
      schizophrenia. P300 effect size (d) was smaller in amplitude and longer in
      latency in schizophrenic patients compared to normal controls, with the strongest
      effects obtained from the auditory oddball. Paranoid subtype demonstrated larger
      P300 amplitude effect sizes than other disease subtypes, and P300 latency effect
      size decreased with disease duration. Psychopathology severity and antipsychotic
      medications were unrelated to P300 amplitude effect size. Gender proportion,
      educational level, and stimulus and task variables also affected P300 amplitude
      and latency effect sizes. The findings are used to formulate a theoretical
      account of the empirical data and provide suggestions for maximizing the utility
      of the P300 component in the assessment of schizophrenia.

PMID- 14696724
TI  - Event-related potential correlates of impaired visuospatial working memory in
      schizophrenia.
AB  - Previous studies have reported that patients with schizophrenia demonstrate
      impaired performance during working memory (WM) tasks. The current study aimed to
      determine whether WM impairments in schizophrenia are accompanied by reduced slow
      wave (SW) activity during on-line maintenance of mnemonic information. Event
      related potentials were obtained from patients with schizophrenia and well
      controls as they performed a visuospatial delayed response task. On 50% of
      trials, a distractor stimulus was introduced during the delay. Compared with
      controls, patients with schizophrenia produced less SW memory negativity,
      particularly over the right hemisphere, together with reduced frontal enhancement
      of SW memory negativity in response to distraction. The results indicate that
      patients with schizophrenia generate less maintenance phase neuronal activity
      during WM performance, especially under conditions of distraction.

PMID- 14696725
TI  - Heart rate variability in acute psychosis.
AB  - Heart rate variability (HRV) provides reliable tools to assess the integrity and
      reactivity of autonomic nervous function. Our aim was to examine HRV in the
      resting condition and during different mental loads in acute psychosis compared
      to healthy controls. HRV was measured in 17 first-episode drug-naive patients
      with psychosis and 21 healthy controls during oddball tasks and while performing
      the Wisconsin Card Sorting Test. A discrete event series was constructed by an
      adaptive QRS detector algorithm and power spectrum estimation was carried out.
      The RMSSD (representing interval differences of successive heartbeats) and the
      amount of high frequency (HF) power were significantly reduced in patients.
      Moreover, the patients' HRV remained unaltered during the tasks, whereas in
      controls the HRV diminished with increasing mental load of the task. Patients
      with psychosis displayed less short-term HR reactivity than healthy controls.
      They also failed to adapt HRV according to the task-connected strain. Acute
      psychosis is characterized by a limited capacity to respond to external demands
      at the level of autonomic nervous system.

PMID- 14696726
TI  - Heritability and "environmentability" of electroencephalogram in infants: the
      twin study.
AB  - We estimated relative contribution of genetic and environmental factors to
      electroencephalogram (EEG) frequency and amplitude parameters in infants. EEG was
      registered in 49 pairs of monozygotic and 45 pairs of dizygotic twins aged 7-12
      months during (1) visual attention and (2) darkness. The variability of occipital
      alpha frequency depended mainly on genetic, probably nonadditive factors. The
      mean heritability for the spectral amplitudes in the delta, theta, and alpha
      bands were 0.37, 0.13, and 0.22 during visual attention, and 0.22, 0.40, and 0.10
      during darkness. The influence of shared environment was probable for many of the
      EEG parameters. It was greatest for the amplitude of the theta rhythm during
      visual attention. The theta amplitude depended on such a parameter of early
      social environmental enrichment as the number of caregivers in the family. The
      possible relationship between infant theta rhythm and developmental outcome is
      discussed. For many of the EEG parameters, heritability increased during the
      second half of the first year of life, thus supporting the hypothesis about
      amplification of genetic effects and decrease of common environmental influences
      with age.

PMID- 14696727
TI  - Let's face the music: a behavioral and electrophysiological exploration of score
      reading.
AB  - This experiment was carried out to determine whether reading diatonic violations
      in a musical score elicits similar endogenous ERP components when hearing such
      violations in the auditory modality. In the behavioral study, musicians were
      visually presented with 120 scores of familiar musical pieces, half of which
      contained a diatonic violation. The score was presented in a measure-by-measure
      manner. Self-paced reading was significantly delayed for measures containing a
      violation, indicating that sight reading a violation requires additional effort.
      In the ERP study, the musical phrases were presented in a "RSVP"-like manner. We
      predicted that diatonic violations would elicit a late positive component.
      However, the ERP associated with the measure where a violation was presented
      showed a negativity instead. The negativity started around 100 ms and lasted for
      the entire recording period. This long-lasting negativity encompassed at least
      three distinct effects that were possibly related to violation detection, working
      memory processing, and a further integration/interpretation process.

PMID- 14696728
TI  - Developmental differences in behavioral and event-related brain responses
      associated with response preparation and inhibition in a go/nogo task.
AB  - The present study investigated developmental trends in response inhibition and
      preparation by studying behavior and event-related brain activity in a cued
      go/nogo task, administered to nine-year-old children and young adults. Hits,
      false alarms, inattention, and impulsivity scores and ERP measures of inhibition
      (fronto-central nogo-N2 and P3), target selection (parietal go-nogo P3
      difference), and response preparation (contingent negative variation; CNV) were
      collected. Higher false alarm and impulsivity scores and the absence of the
      fronto-central nogo P3 all suggest a developmental lag in response inhibition in
      children. A developmental lag in sustained attention processes was suggested by
      worse target detection and larger parietal target/nontarget P3 effects in
      children. Cue orientation and response preparation processes were respectively
      measured by early and late CNV activity. Children displayed smaller early CNV
      amplitudes at fronto-central locations, but mature late CNV. The smaller early
      CNV activity might indicate inefficient cue-orientation processes caused by
      incomplete frontal lobe development.

PMID- 14696729
TI  - Effects of artificial and natural baroreceptor stimulation on nociceptive
      responding and pain.
AB  - The arterial baroreflex may mediate hypertensive hypoalgesia. Carotid
      baroreceptors can be artificially stimulated by neck suction and inhibited by
      compression. Effects of brief neck suction and compression on nociceptive
      responding and pain were studied in 25 normotensive adults. The sural nerve was
      electrocutaneously stimulated at threshold intensity during systole or diastole
      combined with neck suction, neck compression, or no pressure. Nociceptive
      responding was indexed by electromyographic activity elicited in the biceps
      femoris. Participants rated the intensity of sural stimulation. Although
      artificial baroreceptor stimulation (suction) did not affect nociceptive
      responding, baroreceptor inhibition (compression) reduced pain ratings. In
      contrast, natural baroreceptor stimulation during systole reduced nociceptive
      responding compared to diastole, but did not affect pain ratings. The data
      provide partial support for baroreflex modulation of pain.

PMID- 14696730
TI  - Event-related potentials reveal involuntary processing of orientation changes in
      the visual modality.
AB  - The present study investigated whether there is a visual counterpart of the
      auditory mismatch negativity. Event-related potentials were recorded while
      subjects performed a spatial frequency discrimination task. "Match" and
      "nonmatch" stimuli were specifically categorized according to whether the second
      stimulus had the same orientation as the first stimulus in each trial. Nonmatch
      stimuli elicited larger occipital P84 and occipital and temporal N192 components
      than match stimuli, indicating the existence of involuntary processing in the
      visual modality. Moreover, the amplitude of the change-related N 192 was larger
      at the short stimulus onset asynchrony (SOA) than at the long SOA, suggesting
      that the visual modality involves a mismatch process similar to that of the
      auditory modality. The underlying neural representation (i.e., the visual memory
      trace) seems to develop easier and decay faster than its auditory counterpart.

PMID- 14696731
TI  - Effects of positive and negative affect on electromyographic activity over
      zygomaticus major and corrugator supercilii.
AB  - Pleasant stimuli typically elicit greater electromyographic (EMG) activity over
      zygomaticus major and less activity over corrugator supercilii than do unpleasant
      stimuli. To provide a systematic comparison of these 2 measures, the authors
      examined the relative form and strength of affective influences on activity over
      zygomaticus major and corrugator supercilii. Self-reported positive and negative
      affective reactions and facial EMG were collected as women (n = 68) were exposed
      to series of affective pictures, sounds, and words. Consistent with speculations
      based on known properties of the neurophysiology of the facial musculature,
      results revealed a stronger linear effect of valence on activity over corrugator
      supercilii versus zygomaticus major. In addition, positive and negative affect
      ratings indicated that positive and negative affect have reciprocal effects on
      activity over corrugator supercilii, but not zygomaticus major.

PMID- 14696732
TI  - Action monitoring in motor control: ERPs following selection and execution errors
      in a force production task.
AB  - Action monitoring has been studied in many tasks by means of measuring the error
      related negativity (Ne/ERN), but never in a motor control task requiring precise
      force production. Errors in discrete choice reaction tasks are the result of
      incorrect selections, but errors in force production can also arise from
      incorrect executions. ERPs were obtained while participants produced low or high
      isometric forces with their left or right hand. As expected, incorrect choices of
      hand elicited an Ne/ERN. Interestingly, Ne/ERNs were also present in the less
      discrete selection error of an incorrect choice of force, but only when
      erroneously a low instead of a high force was chosen. In both force ranges, no
      Ne/ERNs were found after errors in execution. These errors showed a large
      positivity in feedback ERPs and, similar to correct responses, a prolonged
      negativity in response ERPs. We propose that, compared to selection errors, the
      time uncertainty aspects of execution errors and the resulting changing response
      representations prohibit error detection by the internal monitoring system
      responsible for generating the Ne/ERN.

PMID- 14696733
TI  - The nature of unilateral motor commands in between-hand choice tasks as revealed
      by surface Laplacian estimation.
AB  - From electroencephalographic recordings, we estimated the surface Laplacian over
      motor areas in a Stroop-like between-hand choice reaction time task in humans.
      Response-locked averages showed a (negative) "motor potential" over the primary
      motor areas contralateral to the response. At the same time, a positive wave was
      observed over the primary motor areas ipsilateral to the response. These data
      suggest that, when a between-hand choice is required, an inhibition of the
      primary motor cortex ipsilateral to the nonresponding hand is implemented. This
      observation is relevant to the interpretation of the lateralized readiness
      potential (LRP) because the LRP is blind to the respective contribution of the
      contralateral and ipsilateral motor cortices. In addition, a negative wave
      beginning about 200 ms before EMG onset and peaking about 50 ms before it
      occurred over the supplementary motor areas (FCz). This wave preceded the motor
      potential, which supports the view that the supplementary motor areas are
      upstream in a hierarchy of the motor command.

PMID- 14696734
TI  - Early processing stages are modulated when auditory stimuli are presented at an
      attended moment in time: an event-related potential study.
AB  - The present study investigated with event-related potentials whether attending to
      a moment in time modulates the processing of auditory stimuli at a similar early,
      perceptual level as attending to a location in space. The participants listened
      to short (600 ms) and long (1,200 ms) intervals marked by white noise bursts. The
      task was to attend in alternating runs either to the short or to the long
      intervals and to respond to rare offset markers that differed in intensity from
      the frequent standard offset markers. Prior to the to-be-attended moment, a slow
      negative potential developed over the frontal scalp. Stimuli presented at the
      attended compared to the unattended moments in time elicited an enhanced N1 and
      an enhanced posteriorly distributed positivity (300-370 ms). The results show
      that attention can be flexibly controlled in time and that not only late but also
      early perceptual processing stages are modulated by attending to a moment in
      time.

PMID- 14696735
TI  - Effects of information and reward on stimulus-preceding negativity prior to
      feedback stimuli.
AB  - The purpose of the present study was to investigate the effects of informational
      and motivational level of feedback stimuli on the stimulus-preceding negativity
      (SPN). In the time estimation task, in which a visual stimulus was presented 3 s
      after a voluntary movement, (a) the information level (high information and low
      information) and (b) the motivation level (reward and no-reward) for feedback
      stimuli were manipulated. Under the high-information condition, subjects received
      feedback information about (1) correctness (correct or incorrect), (2) direction
      of error (under- or overestimate), and (3) degree of accuracy (accurate or less
      accurate) of their time estimation. In the low-information condition, however,
      they received information about the correctness only. In the reward condition,
      they received a monetary reward for accurate time estimations but received
      nothing in the no-reward condition. The results demonstrated a significant
      interaction of information by motivation level, showing that the SPN amplitude
      under the reward/high-information was larger than that in the no-reward/high
      information condition. The results are discussed in terms of emotional
      anticipation, taking into consideration the result of self-report that subjects
      felt to be more motivated when they received precise information.

PMID- 14696736
TI  - Early posterior ERP components do not reflect the control of attentional shifts
      toward expected peripheral events.
AB  - Previous experiments investigating ERP correlates of anticipatory attention
      shifts triggered by central symbolic cues have identified a contralateral "early
      directing attention negativity," which was assumed to be generated by processes
      involved in the control of spatial orienting. Here we demonstrate that this
      component is not directly linked to the control of attentional shifts, but
      instead reflects the selection of task-relevant aspects of cue stimuli. In
      contrast, later ERP components triggered during covert attentional shifts are
      insensitive to physical cue attributes, and thus appear to be genuine
      electrophysiological correlates of covert attentional control mechanisms.

PMID- 14696737
TI  - The dental workforce in Europe (or most of it!).

PMID- 14696738
TI  - An assessment of the cost effectiveness of a postal toothpaste programme to
      prevent caries among five-year-old children in the North West of England.
AB  - OBJECTIVE: To assess the cost effectiveness of a postal toothpaste programme to
      prevent caries in 5-year-old children in the north west of England. PARTICIPANTS:
      Birth cohorts of children aged 12 months were recruited from high caries risk
      populations in nine health districts. DESIGN: The results of a randomised
      controlled trial to measure the effects of a postal toothpaste programme are used
      and related to the costs of running a similar programme. Children in the trial
      received free toothpaste on four occasions a year and a toothbrush once a year
      for four years from age 12 months to 5 years. When aged 5-6 years children were
      examined by trained, calibrated examiners using BASCD standards. Those who
      received toothpaste containing 1450 ppm F were found to have a significantly
      lower mean dmft than those who had not. The costs that would be incurred by a
      public dental service running such a postal toothpaste programme are identified,
      measured and related to the likely health improvement that could be achieved.
      MAIN OUTCOME MEASURES: The cost per tooth saved and the cost per child saved from
      caries experience and extraction experience. RESULTS: The estimated cost per
      tooth saved from carious attack was pounds sterling 80.83 and the cost per child
      of preventing caries experience was pounds sterling 424.38 and avoiding any
      extractions was pounds sterling 679.01. Analysis resulted in an overestimation of
      costs and underestimation of benefits. CONCLUSION: The programme achieved a
      significant caries reduction in children who received the 1450 ppm F toothpaste
      and the costs are now available to those considering provision of treatment
      services in areas where children are at high caries risk.

PMID- 14696739
TI  - Changing oral health status of 6- and 12-year-old schoolchildren in Portugal.
AB  - AIMS: To assess the actual oral health status of Portuguese schoolchildren aged 6
      and 12 years according to gender and urbanisation, to highlight the trend over
      time in dental caries prevalence of children, to assess the dental care habits
      and the provision of preventive services to children, and to analyse the effect
      of dental care habits on caries experience. BASIC RESEARCH DESIGN: Clinical
      examinations of oral health status were carried out in 1999 according to WHO
      criteria and included dental caries, enamel lesions, oral hygiene status (OHI-S)
      and Community Periodontal Index (CPI). Structured questionnaires for interviewing
      children on dental care habits and participation in preventive programmes at
      school were used. The study comprised 799 6 year olds and 800 12 year olds.
      RESULTS: In 1999, the prevalence proportion rates of dental caries were 46.9% in
      6 year olds and 52.9% in 12 year olds. Dental caries experience was 2.1 dmf-t and
      1.5 DMF-T, respectively. Significant reductions in caries prevalence rates took
      place over time; in 1984 the mean dmf-t of 6 year olds was 5.2 and for 12 year
      olds it was 3.7 DMF-T. Enamel opacities were found for 7.2% of children and 2.1%
      had moderate dental fluorosis. At age 12, 90% of children had poor oral hygiene,
      i.e. CPI Score 2 (bleeding and calculus). Toothbrushing twice a day was reported
      for 31% of 6-year-olds and 55.6% of 12-year-olds; 17.8% of children aged 6 had
      seen a dentist during the past year and this was found to be 58.3% at age 12.
      Substantial proportions of the children received preventive dental services in
      school. Multivariate analysis of dental caries experience showed that gender,
      location, nationality, dental visits and frequency of toothbrushing were
      significant independent variables. CONCLUSIONS: Further implementation of school
      based oral health promotion and application of population-directed preventive
      strategies are needed in Portugal.

PMID- 14696740
TI  - Factors associated with root caries incidence in an elderly population.
AB  - OBJECTIVE: To identify baseline factors associated with future root caries
      development in an elderly population. BASIC RESEARCH DESIGN: Oral health and
      general health status examinations were carried out at baseline and after one and
      two years. In order to identify risk predictors of root caries with a different
      degree of robustness, three multiple logistic regression analyses where the
      dependent variables were one, two and three or more disease events were
      performed. PARTICIPANTS: Six hundred noninstitutionalised adults aged 70 in
      Niigata, Japan took part in the baseline examination. A total of 373 subjects
      were followed up for two years and identified as dentate at the two-year
      examination. RESULTS: During the period of study, 35.9% of subjects developed at
      least one new root caries lesion. The mean number of new root caries lesions per
      subject was 0.9 (sd = 1.7). Logistic regression analyses indicated that having
      one or more root D surface and mean LA > or = 3.6 mm were the most robust risk
      predictors, having two or more prosthetic crowns, non use of interdental brushes
      or dental floss and LB > or = 10(5) CFU/ml were moderately robust risk
      predictors, and a Body Mass Index < 20 was the least robust risk predictor.
      CONCLUSIONS: These findings suggest that oral health status is a good risk
      predictor, and poor general health indicated by a low Body Mass Index may also
      contribute to root caries occurrence in this elderly population.

PMID- 14696741
TI  - Awareness of tooth erosion in 12 year old children and primary care dental
      practitioners.
AB  - OBJECTIVES: To compare the knowledge of tooth erosion in a sample of 12 year old
      children with that of the dentists responsible for their care and also to compare
      the giving and receiving of advice concerning erosion. METHOD: A random sample of
      1753 children from all 62 state maintained schools in Leicestershire completed
      questionnaires. Questionnaires were also sent to the 257 General Dental
      Practitioners in Leicestershire. RESULTS: 1686 (96.2%) of children and 227
      (82.5%) of dentists returned forms that could be analysed. 36% of dentists
      reported that they frequently noticed erosion on the teeth of their patients but
      67.7% of dentists believed that less than 25% of 12 year olds had any erosion.
      67.5% of dentists advised their patients about erosion only occasionally or
      rarely. Only 34.2% of the children had heard of tooth erosion and only 8.4% could
      recall their dentist mentioning the condition. 40% of children believed that the
      best way to avoid erosion was regular tooth brushing. CONCLUSION: The levels of
      awareness were low for both dentists and patients and the messages that were
      given by dentists were either forgotten or misunderstood by the children, or they
      were incorrect. Better communication and understanding is needed in this
      important area.

PMID- 14696742
TI  - Self-reported oral hygiene practices among adults in Denmark.
AB  - OBJECTIVES: To assess the present level of oral hygiene practices in the Danish
      adult population aged 16 or above, in particular to analyse how self-care
      practices in terms of oral hygiene habits and cleaning of dentures are affected
      by socio-economic factors, dental status, actual dental visiting habits, and the
      experience of oral health care during school years. BASIC RESEARCH DESIGN AND
      PARTICIPANTS: A cross-sectional study of 5802 persons, randomly sampled amongst
      the Danish population aged 16 years or above. Data were collected by means of
      personal interviews and self-administered questionnaires. The response rate was
      66%. RESULTS: Toothbrushing twice-a-day was reported by 68% of the dentates while
      32% brushed their teeth once-a-day or less frequent. Daily use of toothpicks was
      reported by 28% while daily use of dental floss was reported by 11%. Oral hygiene
      habits were more frequent amongst women. Toothbrushing twice-a-day was related to
      regular dental visits, dental care during school years, and a high level of
      education. Daily use of toothpicks was more common among females and older
      persons. Regular dental visits, having 20 or more teeth in situ, and regular
      dental service through school years were predictors for daily use of toothpicks.
      Amongst denture wearers, one-third cleaned their dentures twice-a-day. Frequency
      of denture cleaning was significantly associated with gender, age, number of
      teeth left, and educational level. CONCLUSION: Intensive population-directed
      strategies for oral health education should be considered in order to further
      improve the oral hygiene practices of the entire population.

PMID- 14696743
TI  - Prevalence of oral impacts in a Sinhala-speaking older population in urban Sri
      Lanka.
AB  - OBJECTIVES: To assess the impact of oral conditions on the quality of life in an
      urban older population in Sri Lanka. DESIGN: A cross-sectional study where the
      data were collected by means of an interviewer-administered questionnaire.
      PARTICIPANTS: A total of 585 Sinhala speaking older adults aged 60 years and
      above who were residents of a densely populated urban area. Of the 585, 475 were
      living at home and 110 were living in institutions. OUTCOME MEASURES: Psycho
      social and functional impacts of oral conditions were assessed using the
      Sinhalese translation of the OHIP-14 scale. RESULTS: 25% of subjects had
      experienced one or more impacts due to their oral conditions fairly often or very
      often during the preceding 6 months. Multiple impacts were reported by 17% of the
      subjects. The most commonly experienced impact item was "uncomfortable to eat"
      (17%). The mean OHIP score was 0.8 +/- 1.8. The prevalence of oral impacts and
      the OHIP scores were significantly associated with age, perceived oral health
      status, perceived need for dental care and dental visiting patterns. Those who
      visited a dentist during the past 12 months reported significantly more impacts
      than those who did not visit. CONCLUSIONS: Oral impacts that affected the quality
      of life were relatively common in this sample of older individuals.

PMID- 14696744
TI  - Translation and validation of an Arabic version of the UK oral health related
      quality of life measure (OHQoL-UK) in Syria, Egypt and Saudi Arabia.
AB  - OBJECTIVE: The aim of this study was to translate and evaluate the performance of
      an oral health related quality of life measure--an Arabic version of OHQoL-UK in
      three middle eastern countries: Syria, Egypt and Saudi Arabia. BASIC RESEARCH
      DESIGN: Following forward and backwards translation of OHQoL-UK into Arabic and
      pilot testing the Arabic version among focus groups, a questionnaire containing
      the instrument was administered to 1,000 adults from the three Arab countries. In
      addition, the study participants were interviewed about their oral health status,
      experience of oral health problems in the past year, self-rating of oral health
      and also some socio-demographic information was collected. RESULTS: Among the
      three study populations, variations in OHQoL-UK scores were apparent in relation
      to socio-demographic factors (p<0.01), self-reported number of teeth possessed
      (p<0.001) and experience of oral health problems in the past year (p<0.01) which
      supports the construct validity of the instrument. Furthermore, variations in
      OHQoL-UK scores were apparent in relation to self-rating of oral health status
      (p<0.01) which supports the criterion validity of the measure. The internal
      reliability of the instrument was high in the three groups with Cronbach alpha
      values of above 0.90, indicating good internal consistency. CONCLUSION: The
      Arabic version of OHQoL-UK, an index of oral health related quality of life
      demonstrated satisfactory construct validity, criterion validity and internal
      reliability in Syria, Egypt and Saudi Arabia. This provides further evidence of
      the instrument's psychometric properties and its cross cultural use.

PMID- 14696745
TI  - Promoting sugar-free medicines: evaluation of a multi-faceted intervention.
AB  - OBJECTIVE: To evaluate an intervention to increase the proportion of medicines
      prescribed as sugar-free formulations by general practitioners. BASIC RESEARCH
      DESIGN: Natural experiment. SETTING: Interventions were set in Camden and
      Islington Health Authority with comparator data within that and adjacent health
      authorities. PARTICIPANTS: General medical practices. INTERVENTIONS: Two
      interventions were employed. A prescribing incentive scheme that used the
      proportion of medicines prescribed as sugar-free formulations as a quality marker
      for general practitioners and a publicity campaign for health care workers and
      members of the public. MAIN OUTCOME MEASURES: The proportions of amoxycillin
      mixture and all paracetamol liquid preparations that were prescribed in sugar
      free formulations. RESULTS: Sugar-free prescribing in the practices participating
      in the incentive scheme increased from 27% to 45% whereas non-participating
      practices showed a decrease from 20% to 14%. The proportion of prescriptions for
      sugar-free formulations increased by approximately one half across the entire
      health authority so that after two years Camden and Islington had the highest
      level of prescribing of sugar-free paracetamol and amoxycillin in London.
      CONCLUSION: These data provide compelling evidence of the effectiveness of the
      prescribing incentive scheme whereas the publicity campaign did not change
      prescribing behaviour.

PMID- 14696746
TI  - Validation methodology in publications describing epidemiological registration
      methods of dental caries: a systematic review.
AB  - OBJECTIVE: The aim was to describe and systematically review the methodology and
      reporting of validation in publications describing epidemiological registration
      methods for dental caries. BASIC RESEARCH METHODOLOGY: Literature searches were
      conducted in six scientific databases. All publications fulfilling the
      predetermined inclusion criteria were assessed for methodology and reporting of
      validation using a checklist including items described previously as well as new
      items. The frequency of endorsement of the assessed items was analysed. Moreover,
      the type and strength of evidence, was evaluated. MAIN OUTCOME MEASURES:
      Reporting of predetermined items relating to methodology of validation and the
      frequency of endorsement of the assessed items were of primary interest. RESULTS:
      Initially 588 publications were located. 74 eligible publications were obtained,
      23 of which fulfilled the inclusion criteria and remained throughout the
      analyses. A majority of the studies reported the methodology of validation. The
      reported methodology of validation was generally inadequate, according to the
      recommendations of evidence-based medicine. The frequencies of reporting the
      assessed items (frequencies of endorsement) ranged from four to 84 per cent. A
      majority of the publications contributed to a low strength of evidence.
      CONCLUSION: There seems to be a need to improve the methodology and the reporting
      of validation in publications describing professionally registered caries
      epidemiology. Four of the items assessed in this study are potentially
      discriminative for quality assessments of reported validation.

PMID- 14696747
TI  - Pure red cell aplasia secondary to treatment with erythropoietin.
AB  - Pure red cell aplasia (PRCA) is a rare condition defined as severe anemia
      secondary to the virtual absence of red blood cell precursors in the bone marrow.
      In the setting of patients treated with rHuEPO, the disease is generated by
      epoetin-induced antibodies that neutralise all the exogenous rHuEPO and cross
      react with endogenous erythropoietin. As a result, serum erythropoietin levels
      are undetectable and erythropoiesis becomes ineffective. Only 4 cases of PRCA
      associated with rh-EPO have been reported before 1998. Thereafter, a sharp
      increase in the incidence of this rare condition has been reported, mainly
      associated with epoetin alpha use outside the United States. A number of possible
      mechanisms leading to PRCA development have been identified. Among these,
      modification of drug formulation and down stream processing probably has had a
      major role. Indeed, in 1998 the formulation of epoetin alpha in Europe was
      modified because of the fear of the "mad cow" syndrome. However, differences in
      molecule structure and glycosylation among different epoetins can not be
      excluded. It should also be underlined that the rise in the incidence of PRCA
      cases has been coincident with a major shift from intravenous to subcutaneous
      administration of rHuEPO. The abrupt rise in the incidence of PRCA cases observed
      in the last few years, deserves particular attention; however, we have to balance
      its severity, but extreme rarity, with the high number of chronic kidney disease
      patients who die each year because of cardiovascular disease that could partially
      be reduced by anemia treatment.

PMID- 14696748
TI  - Kinetics of hepatitis C virus load during hemodialysis: novel perspectives.
AB  - Hepatitis C virus (HCV) infection remains frequent among dialysis patients. The
      relationship between viral load and liver disease progression is currently a
      matter of debate; however, low HCV viral load (HCV RNA) is a well established
      predictor of successful antiviral treatment. Dialysis patients have immune
      compromise due to uremia; in spite of this, HCV viral load is not high and does
      not increase over time. A number of studies support the notion that this dynamics
      of HCV viral load may be related to lowering of HCV RNA titers during the HD
      procedure. It has been suggested that the intradialytic reduction of HCV is
      membrane-dependent; polysulphone (PS) and hemophan membranes appear more
      effective. Various mechanisms have been mentioned to explain the reduction of HCV
      RNA during hemodialysis (HD): adsorption of HCV onto dialysis membrane, HCV
      escape into spent dialysate, destruction of HCV particles or increased interferon
      (IFN) activity. Several investigators have noted that, at the end of the HD
      procedure, a virological rebound of HCV viremia occurs. Some suggestions have
      been made to minimize the risk for HCV escape into spent dialysate. However,
      controversial evidence on these issues exists: the HCV RNA reduction during HD
      procedures has not been seen in some studies and the relationship between the
      intra-dialytic reduction of HCV RNA titers and dialysis membrane is not
      completely understood. It is evident that additional long-term longitudinal
      studies by serial viral load estimations are needed to better define the dynamics
      of HCV viral load in the dialysis population.

PMID- 14696749
TI  - The challenge of cardiovascular risk factors in end-stage renal disease.
AB  - Due to the impressive cardiovascular (CV) morbidity and mortality in uremic
      patients, assessment of CV risk factors in the dialysis population is a crucial
      challenge in nephrology. Cardiovascular risk factors in dialysis patients may
      have a different significance in ESRD patients compared to the general
      population. The Framingham risk equation seems not to be valid in chronic uremia.
      Furthermore, new powerful outcome predictors have emerged in recent years: pulse
      pressure, dipping status, pulse wave velocity, augmentation index. The concept of
      "U"-shaped association between blood pressure (as well as cholesterolemia) and
      mortality are extensively discussed. The authors are focusing on the value of
      office and ambulatory blood pressure measurements in the uremic population. An
      extensive evaluation of blood pressure and vascular compliance in dialysis
      patients is proposed. Efficient dialysis, ACE-inhibitors and beta-blockers,
      statins, antiplatelet treatment and adequate control of calcium-phosphorus
      metabolism should be the mainstay of therapy in the ESRD patients with several CV
      risk factors.

PMID- 14696750
TI  - Clinical and therapeutic aspects of diabetic nephropathy.
AB  - The prognosis of renal survival in both type 1 and type 2 diabetes mellitus is
      not benign. Several factors characterize the increase in the risk of developing
      renal damage in diabetic patients, distinguished in diabetes-related factors,
      genetic factors and other factors. DIAGNOSIS: Diagnosis requires standard annual
      urinalysis and dipstick for albumin. In patients with negative urine dipstick,
      the routine approach is to evaluate the albumin/creatinine ratio (ACR) in the
      first voided urine. The degree of renal impairment is assessed by an annual
      evaluation of the glomerular filtration rate (GFR) by the Cockroft/Gault formula
      in normoalbuminuric patients. In patients with overt nephropathy this evaluation
      needs to be more frequent. THERAPY: A thorough therapeutic approach, in both the
      early and later stages of diabetic nephropathy, is fundamental because of the
      increased risk of morbidity and mortality. Renal damage (and the natural history
      of the disease) is approached on three different levels. Primary prevention, in
      patients with no clinical and biochemical signs of renal damage, is a strict
      glycemic control by oral antidiabetic agents or insulin, as required, together
      with the maintenance of blood pressure (BP) levels < 130/85 mmHg, preferably
      using ACE-inhibitors. Secondary prevention aims to prevent or slow the
      progresssion from micro- to macroalbuminuria. BP control is the first-line
      approach, along with a strict glycemic control. At this stage, it is necessary to
      use other anti-hypertensive agents besides ACE-inhibitors to achieve optimal BP
      levels of 130/85 mmHg. Tertiary prevention addresses the reduction in the rate of
      renal failure progression by optimal BP control, a slightly hypoproteic diet and
      the control of dyslipidemia, in the presence of a (non-fundamental) euglycemic
      state. PROMISING NEW TRENDS IN DIABETIC NEPHROPATHY TREATMENT: a pharmacological
      blockade of endothelin and/or sympathetic system, an amelioration of hypoxia by
      correcting reduced hemoglobin levels, an interference with the formation and
      accumulation of advanced glycosilation end-products (AGE). Finally, the
      manipulation of the sex hormone balance, genetic screening for a predisposition
      to progressive renal dysfunction and, eventually, gene therapy complete the
      scenario for future approaches to this major complication of diabetic disease.

PMID- 14696751
TI  - An evidence-based disease-management program for patients with diabetic
      nephropathy.
AB  - BACKGROUND: In Germany, a surge in the number of dialysis patients is expected
      over the next 10 years. This article aims to: (1) address this trend by
      developing an evidence-based disease-management program for patients with
      diabetic nephropathy and; (2) to identify areas for future research on disease
      management tools. METHODS: We conducted a systematic search of studies published
      between January 1966 and December 2001 investigating the relationship between
      disease management tools and clinical and economic outcomes of patients with
      diabetic nephropathy. Studies were categorized according to level of scientific
      evidence. As a disease management tool when scientific evidence was lacking,
      expert judgement was used. RESULTS: We identified 10 studies that formed the
      scientific basis of this program's recommendations. For patients with incipient
      or clinical nephropathy the program recommends the implementation of clinical
      guidelines, patient feedback to physicians and treatment documentation. For
      predialysis patients it suggests that specialists or a team of specialists
      coordinate patient care. Further, the program recommends educational sessions,
      use of case managers and regular quality circles for dialysis patients. Trial
      evidence suggests that the prospect of cost-saving is greatest for the management
      of pre-dialysis patients. CONCLUSIONS: High-quality studies on the use of many
      disease management tools are lacking, for example, on the role of case managers
      and primary care physicians in non-dialysis patients. To keep costs manageable
      the disease-management program can begin with enrolling predialysis patients.

PMID- 14696752
TI  - Family history of end-stage renal disease among hemodialyzed patients in Poland.
AB  - BACKGROUND: In previous reports of end-stage renal disease (ESRD) patients,
      family history of ESRD was associated with race, younger age, higher education
      levels and ESRD etiology. This study aimed to analyze how often Polish caucasian
      dialysis patients reported relatives with ESRD, and to evaluate which risk
      factors are associated with family history of ESRD. METHODS: 4808 ESRD patients
      provided data about renal disease etiology, diabetes and hypertensive status of
      first- and second-degree relatives, socioeconomic status and education level.
      RESULTS: Reported ESRD etiologies were: chronic glomerular disease, 19.4 %;
      diabetic nephropathy, 11.3%; interstitial nephritris, 11.2%; hypertension, 7.8%;
      polycystic kidney disease (PKD), 7.1%; other or no response, 40.0%. Positive ESRD
      family history was reported by 745 patients (15.5%); positive history of
      diabetes, 932 (19.4%); hypertension, 1904 (39%). Positive ESRD family history
      according to kidney disease etiology was: PKD, 53.1%; glomerulonephritis, 12%;
      diabetic nephropathy, 11.9%; hypertension, 11.8%; interstitial nephritis, 10.8%.
      PKD as ESRD etiology (odds ratio (OR) 8.06, 95% confidence interval (CI) 6.35
      10.23, p < 0.0001), positive family history of diabetes (OR 1.64, 95% CI 1.34
      1.99, p < 0.0001) and positive history of hypertension (OR 1.64, 95% CI 1.39
      1.95, p < 0.0001), were independently associated with positive ESRD history.
      Patients with later ESRD onset had a less frequent positive ESRD family history:
      for ESRD < 45 yrs, 16% (OR 1.0); 45-64 yrs, 14.4% (OR 0.83, 95% CI 0.70-0.99); >
      or = 65 yrs, 9.2 % (OR 0.5, 95% CI 0.35-0.72). CONCLUSIONS: Results of our study
      strongly support the contention that familial predisposition contributes to ESRD
      development.

PMID- 14696753
TI  - Hyperhomocysteinemia and protein damage in chronic renal failure and kidney
      transplant pediatric patients--Italian initiative on uremic hyperhomocysteinemia
      (IIUH).
AB  - BACKGROUND: Plasma homocysteine, a new cardiovascular risk factor in both
      children and adults, is higher in chronic renal failure or kidney transplant
      patients. This alteration has been linked, in chronic renal failure, to plasma
      protein damage, represented by increased L-isoaspartyl residues. We measured
      plasma homocysteine levels and plasma protein damage in pediatric patients from
      four different Italian regions with conservatively treated renal failure;
      hemodialysis, continuous ambulatory peritoneal dialysis (CAPD), or transplants,
      to establish the presence of protein damage and the relative role of
      hyperhomocysteinemia. METHODS: High performance liquid chromatography (HPLC)
      separation measured total plasma homocysteine levels, using precolumn
      derivatization with ammonium 7-fluorobenzo-2-oxa-1, 3-diazole-4-sulphonate (SBD
      F). Plasma protein L-isoaspartyl residues were quantitated using human
      recombinant protein carboxyl methyl transferase (PCMT). RESULTS: In all patient
      groups, homocysteine levels were significantly higher with respect to the control
      (Control: 6.87 +/- 0.73 microM) conservatively treated, 14.19 +/- 1.73 microM;
      hemodialysis, 27.03 +/- 4.32 microM; CAPD, 22.38 +/- 3.73 microM; transplanted,
      20.22 +/- 2.27 microM, p < 0.001 vs. control]. Plasma protein damage was
      significantly higher in conservatively treated, hemodialysis (HD) and CAPD
      patients, while in transplant patients it was no different from the control.
      CONCLUSIONS: We concluded that in pediatric patients of different Italian
      geographical origin, plasma homocysteine levels were significantly higher in all
      groups with respect to healthy children; therefore contributing to the elevated
      cardiovascular risk present in these patients. Plasma protein L-isoaspartyl
      content was higher in renal failure patients, but kidney transplant patients had
      normal levels, indicating that this kind of protein damage relates more to the
      toxic action of uremic retention solutes, than to plasma homocysteine levels.

PMID- 14696755
TI  - Intravenous administration of vitamin B12 in the treatment of
      hyperhomocysteinemia associated with end-stage renal disease.
AB  - BACKGROUND: High serum levels of total homocysteine (tHcy) are common in dialysis
      patients with end-stage renal disease (ESRD). We assumed that these patients may
      have decreased response to conventional folic acid (FOL) and vitamin B12 (B12)
      administered orally. This study aimed to evaluate the efficacy of an intravenous
      (i.v.) B12 regimen in ESRD patients and compare it with the conventional regimen.
      METHODS: We designed an open label, crossover, non-randomized study of 72 ESRD
      patients. Our patients were hemodialyzed in two hospitals (HOSP1 and HOSP2). In
      HOSP1, patients were on 1 mg of FOL and 600 micog of B12 orally for 3 months, and
      then switching to 1 mg of B12 i.v. for 3 additional months, while the FOL dosage
      was constant. In HOSP2, patients received the same treatment in reverse. RESULTS:
      Patients in HOSP1 (n = 37) after i.v. B12 treatment, had significantly lower tHcy
      (p < 0.001) and FOL (p < 0.05) serum levels, compared with those at the end of
      oral B12 treatment. On the contrary in HOSP2 patients, serum tHcy levels
      increased significantly (n = 35, p < 0.0001) when i.v. was switched to oral
      treatment. There was a significant inverse correlation between tHcy and B12 (p <
      0.0001) at the end of the i.v. treatment period; while treatment there was no
      correlation between tHcy and FOL serum levels. At the end of the oral treatment
      period, there was no significant correlation between tHcy and B12 serum levels,
      while tHcy and FOL serum levels had a significant inverse correlation (p =
      0.002). CONCLUSIONS: Our results suggest that ESRD patients on dialysis have 'B12
      resistance', and that they should have, in addition to their FOL therapeutic
      regimen, i.v. B12 treatment to reduce their elevated tHcy levels.

PMID- 14696754
TI  - Controlled trials of very high dose folic acid, vitamins B12 and B6, intravenous
      folinic acid and serine for treatment of hyperhomocysteinemia in ESRD.
AB  - BACKGROUND: Hyperhomocysteinemia is seen in most hemodialysis (HD) patients and
      is an independent risk factor for cardiovascular disease. Homocysteine metabolism
      via remethylation requires activated folate and vitamin B12 and metabolism via
      transsulfuration requires serine and vitamin B6. Prior studies have shown highly
      variable effects of supplemental B vitamin and folate therapy for
      hyperhomocysteinemia. We undertook a fully controlled trial with abnormally high
      doses of folic acid alone or with supplemental vitamin B6 and B12 compared with
      active folate alone or with serine. METHODS: Two prospective studies were
      undertaken in hemodialysis patients. In the first study (protocol A),
      hyperhomocysteinemia was treated in 77 patients with 30 or 60 mg folic acid with
      or without vitamins B6 and B12 for eight weeks and compared with matching
      placebos. In the second study (protocol B), hyperhomocysteinemia was treated in
      37 patients with intravenous folinic acid given alone or with serine and compared
      with matching placebos. All patients received the standard of care treatment with
      a multivitamin tablet before and throughout the protocol to test the hypothesis
      that additional therapy is required over and above the routine therapy for
      maximum reduction in total homocysteine (tHcy). RESULTS: Normal volunteers; The
      mean (SD) tHcy of 128 normal subjects was 6.5 (4) micromol/L. Protocol A; Plasma
      folate increased significantly in the groups given folic acid at both four and
      eight weeks (P = 0.0001 at both time points). Plasma vitamin B12 was
      significantly increased at four weeks (P = 0.0018) but not at eight weeks (P =
      0.064) in those given Vitamin B12. However, tHcy did not differ between treatment
      groups at baseline (P = 0.63), four weeks (P = 0.79) or eight weeks (P = 0.74).
      Protocol B: Plasma folate increased significantly at four weeks in those
      receiving folinic acid (P = 0.0001) but tHcy was not significantly different
      between groups (P = 0.92). In neither study was there any significant change in
      tHcy comparing before and during any treatment intervention. CONCLUSIONS: In our
      studies high dose oral folic acid, intravenous folinic acid, vitamins B6 and B12
      and oral serine were ineffective at lowering tHcy in patients on hemodialysis
      when given folic acid, folinic acid serine or B vitamins in addition to routine
      folic acid and B vitamin supplements.

PMID- 14696756
TI  - Raised plasma total sialic acid levels are markers of cardiovascular disease in
      renal dialysis patients.
AB  - Cardiovascular disease (CVD) rates in dialysis patients are very high. One of the
      many associated risk factors is chronic inflammation. The relationship of
      baseline markers of chronic inflammation with the presence of CVD was assessed in
      a large cohort of stable dialysis patients. Median time (IQR) on dialysis
      treatment was 20(9-52) months. Forty-one patients had CVD (as defined by the
      history / clinical presence of ischemic heart disease, peripheral vascular
      disease, or cerebrovascular disease). Patients with CVD were significantly older
      than patients without (67 + /- 11 vs. 54 + /- 10 yrs, p < 0.03). Time from
      dialysis, urea reduction ratio (hemodialysis only) and smoking history were
      similar between the two groups. Patients with CVD had significantly higher levels
      of sialic acid (SA) (91.2 +/- 24.2 vs. 82.0 + /- 18.2 mg/dL, p = 0.03). Body
      weight, plasma fibrinogen, C-reactive protein (CRP), homocysteine, creatinine,
      total-, LDL (low density lipoprotein)-, or HDL (high density lipoprotein)
      cholesterol, systolic, diastolic and pulse pressures did not differ between the
      CVD and CVD(-) groups. Patients on chronic ambulatory peritoneal dialysis (CAPD)
      had more elevated lipid fractions, inflammatory markers, and SA levels than did
      patients on hemodialysis (HD). The presence of diabetes, the use of lipid
      lowering therapy, and smoking history was not associated with any difference in
      SA levels. In contrast to C-reactive protein (CRP) concentrations, SA levels were
      unaffected by the hemodialysis session. SA was strongly correlated with CRP (r =
      0.59, p < 0.0001), but not with patient age, any measure of blood pressure (BP),
      urea reduction ratio, plasma creatinine, lipid fractions or homocysteine. Levels
      of the chronic inflammation marker sialic acid correlate strongly with CRP and
      are increased in patients with cardiovascular disease, but show no relationship
      to hemodialysis session. Thus sialic acid may be a superior marker to CRP for
      assessment of chronic inflammation in patients undergoing dialysis.

PMID- 14696757
TI  - Epoetin requirement does not depend on dialysis dose when Kt/N > 1.33 in patients
      on regular dialysis treatment with cellulosic membranes and adequate iron stores.
AB  - BACKGROUND: An inverse correlation between Kt/V and epoetin requirement has
      recently been demonstrated in stable hemodialysis (HD) patients with adequate
      iron stores, dialyzed with cellulosic membranes. However, there is no evidence as
      to whether or not this effect continues for Kt/V even in the adequate or higher
      range. METHODS: We investigated the relationship between Kt/V and the weekly
      epoetin dose in 85 stable HD patients (age 63 +/- 16 years) treated with
      bicarbonate HD and unsubstituted cellulose membranes for 6-338 months (median: 70
      months). INCLUSION CRITERIA: HD for at least 6 months, subcutaneous rHuEPO for at
      least 4 months, transferrin saturation (TSAT) > or = 20%, serum ferritin > or =
      100 ng/mL, hemoglobin (Hb) level targeted to approximately equal to 12 g/dL for
      at least 3 months. EXCLUSION CRITERIA: HBsAg and HIV positivity; need for blood
      transfusions or evidence of blood loss in the 3 months before the study, acute
      and chronic infections. To evaluate the effect of dialysis adequacy on the
      epoetin requirement, we also performed the same analysis after dividing of the
      patients according to Kt/V. Hematocrit (Hct) and Hb levels were evaluated weekly
      for 3 weeks; TSAT, serum ferritin, Kt/V, PCRn, serum albumin (sAlb), and weekly
      epoetin dose were evaluated at the end of observation. No change in dialysis or
      therapy prescription was made during the study. RESULTS: The results for all the
      patients were: Hct 36 +/- 2 %, Hb 12 +/- 0.7 g/dL, TSAT 28 +/- 7%, serum ferritin
      234 +/- 171 ng/mL, sAlb 4.2 +/- 0.4 g/dL, Kt/V 1.33 +/- 0.17, PCRn 1.15 +/- 0.28
      g/Kg/day, weekly epoetin dose 117 +/- 74 U/Kg. There was no correlation between
      Hb and Kt/V, whereas there was an inverse correlation between the reciprocal of
      the weekly epoetin dose and Kt/V (r = -0.448, p = 0.0001). Further regression
      line analysis showed a break-point for Kt/V at the level of 1.33. In the 52
      patients with Kt/V < 1.33, the correlation was confirmed between epoetin and Kt/V
      (r = - 0.563, p = 0.0001), while in the 33 patients with Kt/V > or = 1.33, there
      was no correlation between epoetin dose and Kt/V (r = 0.021, p = NS). In these
      patients, multiple regression analysis, with the weekly epoetin dose as a
      dependent variable, confirmed Kt/V as a non-significant factor. CONCLUSIONS: In
      iron-replete HD patients on cellulosic membranes and stabilized epoetin therapy,
      inadequate dialysis was associated with higher epoetin requirement, but for Kt/V
      values > or = 1.33, there was no further effect on epoetin responsiveness.

PMID- 14696758
TI  - Thermal effects of different dialysis techniques and blood pump speeds: an in
      vitro study.
AB  - Thermal effects have a pivotal impact on hemodynamic stability during dialysis
      procedures. In contrast to conventional dialysis techniques, there are no data in
      the literature regarding the thermal energy balance during on-line techniques.
      Secondly, little data exist on the effect of extracorporeal blood pump speed
      (EBPS) on thermal energy balance. In this study we assessed, first, relative
      differences in energy transfer rate (ETR) over the extracorporeal circuit during
      on-line hemo(dia)filtration (H(D)F) procedures and hemodialysis (HD) at different
      dialysate temperatures during an in vitro procedure using a blood temperature
      monitor (BTM). Secondly, we assessed the thermal effects of different blood pump
      speed (BPS) rates during the various treatment modalities. ETR was different
      among all treatment modalities (p < 0.05) studied, except for HD at 36.5 degrees
      C vs. pre-dilution hemofiltration (HF) and post-dilution HDF vs. HD at 37.5
      degrees C. ETR had the most negative result, indicating the largest energy loss,
      during HD at 35.5 degrees C (-58.5.2 +/- 2.6 W), whereas it was almost comparable
      between pre-dilution HF (-30.7 +/- 4.1 W) and HD at 36.5 degrees C (-35.1.2 +/-
      2.4 W). Post-dilution HDF (-17.7 +/- 1.2 W) resulted in an ETR comparable to that
      of HD at 37.5 degrees C (-15.0 +/- 3.9 W). ETR during post-dilution HF was -43.8
      +/- 1.3 W. The thermal effect of the BPS was more pronounced during the
      procedures with the more negative ETR. In conclusion, on-line techniques and BPS
      have widely varying effects on ETR during dialysis, which should be considered
      when the hemodynamic effects among different treatment modalities are compared.

PMID- 14696759
TI  - Role of serum creatinine and prognostic scoring systems in assessing hospital
      mortality in critically ill cirrhotic patients with upper gastrointestinal
      bleeding.
AB  - BACKGROUND: End-stage liver disease is frequently complicated by episodes of
      gastrointestinal hemorrhage that are often associated with multiple organ
      dysfunction and require intensive care. This study aimed to identify specific
      predictors of hospital mortality in critically ill cirrhotic patients with
      gastrointestinal bleeding, and compare the prediction accuracy of the Child-Pugh
      score and two illness severity scoring systems frequently used for intensive care
      unit (ICU) patients. METHODS: 76 patients with liver cirrhosis and upper
      gastrointestinal bleeding were admitted to the ICU from April 2001 to March 2002.
      In addition, 27 demographic, clinical and laboratory variables, including
      parameters assessing liver and renal function and systemic hemodynamics, were
      analyzed as survival predicators. Finally, information required, calculating the
      Child-Pugh, Sequential Organ Failure Assessment (SOFA), and Acute Physiology and
      Chronic Health Evaluation (APACHE) III score on the 1st day of ICU admission, was
      gathered prospectively. RESULTS: Overall, hospital mortality was 68.4%. Liver
      disease was generally attributed to hepatitis B viral infection. Furthermore,
      multiple logistic regression analysis showed that mean arterial pressure (MAP),
      Child-Pugh points, and serum creatinine (Cr) were significantly related to
      prognosis. The SOFA and APACHE III models displayed good areas under the receiver
      operating characteristic (ROC) curve. CONCLUSION: The rise of serum Cr levels
      above 1.5 mg/dL is common, and indicates a poor prognosis for critically ill
      cirrhotic patients with gastrointestinal bleeding. SOFA is a straightforward
      approach with excellent prognostic abilities for this homogeneous patient subset.

PMID- 14696760
TI  - Continuous renal replacement therapies: anticoagulation in the critically ill at
      high risk of bleeding.
AB  - BACKGROUND: The ongoing necessity for systemic heparinization is a well-known
      disadvantage of continuous renal replacement therapies (CRRT), and alternative
      methods of anticoagulation may be required. Our aim was to evaluate, in patients
      with a high risk of bleeding, the possibility of an acceptable filter life with
      non-anticoagulation CRRT and, in case of early filter failure, the efficacy and
      safety of bedside monitored regional anticoagulation with heparin and protamine.
      METHODS: Fifty-nine patients underwent CRRT for acute renal failure (ARF)
      following cardiac surgery. Patients who fulfilled one of the following criteria
      were selected for non-anticoagulation CRRT: spontaneous bleeding, aPTT > 45 sec,
      thrombocytopenia and recent surgery (< 48 hr). Filter life < 24 hr without
      anticoagulation was the cut-off point for starting the regional anticoagulation
      CRRT. Heparin was infused pre-filter and protamine post-filter at an initial
      ratio of 1 mg protamine:100 IU heparin. The ratio was adjusted to achieve a
      patient aPTT < 45 sec and a circuit > 55 sec. RESULTS: Twenty-two (37.3%)
      patients had been selected for non-anticoagulation. Of them, 12 patients
      continued to receive non-anticoagulation (filter life: 38.3 +/- 30.5 hr) while 10
      switched to regional anticoagulation (filter life: 38.6 +/- 25 hr). During
      regional anticoagulation no statistical difference was found between baseline
      aPTT (36.7 +/- 6.4 sec) and patient aPTT (41.5 +/- 12.6 sec) while circuit aPTT
      (77.7 +/- 43.3 sec) was significantly higher than patient aPTT (p < 0.0001). The
      probabilities of the circuits remaining free from clotting after 24, 48 and 72 hr
      were: a) non-anticoagulation: 55.5%, 30.1% and 16.6%, b) regional
      anticoagulation: 76.2%, 39.6% and 19.8%. There was no rebound anticoagulation
      observed after regional anticoagulation CRRT ended. CONCLUSIONS: Non
      anticoagulation CRRT allowed an adequate filter life in most patients with a high
      risk of bleeding for prolonged aPTT and/or thrombocytopenia. Despite concerns
      regarding the need for careful monitoring, regional anticoagulation with heparin
      and protamine can be considered as a safe and valid alternative when non
      anticoagulation is unsuitable because of early filter failure.

PMID- 14696761
TI  - Cost analysis of blood purification in intensive care units: continuous versus
      intermittent hemodiafiltration.
AB  - BACKGROUND: We implemented a program for continuous renal replacement therapies
      (CRRT) in intensive care units (ICU) based on the cooperative work of dialysis
      and ICU personnel. Our aim was to report the main details of this program and
      compare its cost with that of intermittent hemodiafiltration (IHDF). METHODS: The
      study referred to 181 ICU patients with renal failure. We considered the costs of
      both technical devices and assisting personnel. CRRT was performed as continuous
      veno-venous hemodiafiltration (CVVHDF) (24 hr daily); dialysis and ICU nurses
      shared surveillance. Only dialysis nurses performed IHDF (as acetate-free
      biofiltration, 4 hr daily) in the ICU. RESULTS: The daily cost of CRRT was Euro
      276.70; of which 79% was for devices and 21% was for human resources. Nurse
      surveillance required 141 min per day, ICU nurses supplied 55% (77 min) and
      dialysis nurses 45% (64 min). On average, CRRT surveillance required less than 1
      min/nurse/hr for both dialysis and ICU nurses. The daily cost of 4-hr IHDF
      sessions of was Euro 247.83, of which 44% was for technical devices and 56% was
      for human resources. CONCLUSIONS: The cooperation between dialysis and ICUs
      improved the use of human resources and allowed us to supply CRRT to all
      critically ill patients with acute renal failure. The expenditure for CRRT was
      12% higher than that for IHDF, due to the cost of technical devices.

PMID- 14696762
TI  - Tacrolimus-associated hemolytic uremic syndrome: a case analysis.
AB  - BACKGROUND: Tacrolimus is an effective organ transplantation immunosuppressant.
      Hemolytic uremic syndrome (HUS) is a rare but severe complication of tacrolimus.
      METHODS: We report a case of tacrolimus-associated HUS and review the 15
      previously reported cases. RESULTS: The results of the 16 cases indicated that
      tacrolimus-associated HUS is more frequent in females (56.3%), with the mean age
      at onset of 41.3 years. Forty-four percent of cases received renal
      transplantations. The average time from the first tacrolimus dose to HUS onset
      was 7.1 months. Prevalence was between 0.14.7%. The tacrolimus trough level did
      not predict the prognosis. Seven patients (43.7%) had improved graft function
      after treatment, including anticoagulation and antiplatelet therapy, reduction or
      discontinuation of tacrolimus, switch to cyclosporine (CyA), plasma exchange (PE)
      and dialysis. Five patients (31.3%) died and four patients (25%) lost their graft
      in spite of the above treatment. Mortality risk factors for transplant recipients
      with tacrolimus-associated HUS included: (1) non-renal transplant recipients
      (100% vs. 36.4%, p = 0.034); (2) lower peak serum Cr (2.58 +/- 1.23 vs. 6.16 +/-
      1.96, p < 0.002); (3) liver dysfunction (60% vs. 0, p < 0.02); (4) higher serum
      lactate dehydrogenase (LDH) level (3119 +/- 1019 vs. 982 +/- 522, p < 0.001). A
      lower platelet count carried borderline mortality risk (29500 +/- 14480 vs. 59625
      +/- 25584, p = 0.057). CONCLUSIONS: HUS should be included in the differential
      diagnosis of renal function deterioration in patients on tacrolimus post-organ
      transplantation. Frequent renal function monitoring and appropriate treatment
      should be performed aggressively to decrease morbidity and mortality, especially
      in patients with risk factors.

PMID- 14696763
TI  - Successful treatment of hemolytic uremic syndrome after liver-kidney
      transplantation.
AB  - INTRODUCTION: Hemolytic-uremic syndrome (HUS) is a rare complication in organ
      transplantation, characterized by hemolytic microangiopathic anemia,
      thrombocytopenia, and severe renal failure. The syndrome is a well-recognized
      complication in bone marrow transplantation, and has been likewise described in
      several cases of solid organs transplantation, but never in patients receiving
      combined liver and kidney transplantation. CASE REPORT: We describe a case of HUS
      in a 59-year-old woman who underwent combined liver-kidney transplantation for
      hepato-renal polycystic disease. Clinical and laboratory manifestations of the
      syndrome were severe and included renal failure, hemolytic anemia, severe
      thrombocytopenia, hypertension, and neurological damage. The initial treatment
      consisted of withdrawal of cyclosporine, introduction of low-dose tacrolimus, and
      administration of fresh frozen plasma (FFP) transfusion and heparin. Since there
      was no improvement in clinical or biochemical features, plasmapheresis with FFP
      replacement (2000 mL/day) followed by intravenous immunoglobulin (0.4 mg/Kg/day)
      was started. A rapid improvement in renal function, platelet count, and hemolytic
      anemia was observed. CONCLUSIONS: Based on the good response observed in our
      patient, we feel that an aggressive treatment with plasmapheresis and intravenous
      immunoglobulin should be offered to organ transplant recipients with severe HUS.

PMID- 14696764
TI  - CMV and BKV ureteritis: which prognosis for the renal graft?
AB  - This report describes two cases of ureteral stricture in renal graft recipients
      related to cytomegalovirus (CMV) and human polyoma BK virus (BKV) ureteritis with
      the same onset characterized by acute graft failure with no clinical signs of
      systemic viral infections. The histological analysis did not show other causes of
      graft impairment (i.e. drug toxicity and acute rejection). Ultrasound scan (US)
      revealed absent or mild hydronephrosis. The diuretic-MAG3 renal scan showed a
      urinary flow obstruction. The viral genomes were isolated from urine, peripheral
      blood and graft or ureteral tissues samples. A percutaneous nephrostomy confirmed
      the stricture, but it restored urine flow only in the graft affected by CMV
      ureteritis, the association with a specific antiviral therapy probably produced a
      stable restoration of graft function. In BKV ureteritis,the graft prognosis was
      poor; graft loss could be due to the progress of BKV nephropathy. A correct
      differential diagnosis of the etiologic agent responsible for the ureteritis is
      mandatory, because treatment and outcome of the infection are different.

PMID- 14696765
TI  - Spontaneous renal hemorrhage occurring during pregnancy.

PMID- 14696766
TI  - Nanotechnologies and microchips in genetic diseases.
AB  - Microarrays or microchips represent a new area of high technology, which will
      completely change the methodological approach to basic research and clinical
      diagnostics. This technology can be used for genotyping, expression profiling and
      proteome analysis. Genetics and molecular medicine have an expanding need for
      rapid genotyping, mutational analysis and DNA re-sequencing technologies, i.e.
      microarrays that have a clear potential for miniaturization, parallelization, and
      automation and enable high-throughput screening. Expression profiling technology
      is a new tool for investigating expression patterns, identifying new disease
      genes either for monogenic disorders or for complex traits, identifying new
      functional and cellular relationships and identifying new pathways and possible
      related drugs. This technology has been successfully applied to the study of
      complex traits, i.e. cardiovascular diseases, cancer and type II diabetes,
      providing new insights into possible pathogenetic mechanisms and new
      therapeutical approaches. Finally, microarray can further improve proteome
      analysis. This review discusses these points.

PMID- 14696767
TI  - Branchio-oto-renal syndrome.
AB  - Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized
      by the association of branchial cysts or fistulae, external ear malformation
      and/or preauricular pits, hearing loss and renal anomalies. Mutations in the EYA1
      gene, a human homologue of the drosophila "eyes absent" gene, are identified as
      the cause of BOR syndrome.

PMID- 14696768
TI  - Neonatal hypercalcemia.
AB  - The causes of hypercalcemia during the neonatal period are varied. Diagnosis is
      based on the plasma levels of parathyroid hormone (PTH). (a) PTH in plasma is
      diminished; exogenous o r endogenous calcium overloading is suspected. (b) PTH in
      plasma is increased; hyperparathyroidism caused by homozygous or heterozygousloss
      of-function mutations in the CaR gene is suspected. (c) PTH i n plasma is normal;
      low or normal urinary calcium excretion (i.e.relative hypocalciuria) and normal
      PTH plasma levelsare relevant findings of familial hypocalciuric hypercalcemia
      (FHH) syndrome.

PMID- 14696769
TI  - Genetics of human arterial hypertension.
AB  - Although everybody agrees that each individual's blood pressure variance is under
      substantial genetic control, its quantitative estimates vary from 35 to 70%,
      according to the different experimental designs. The problem is that, in spite of
      such substantial contribution, the discovery of the "genes that cause
      hypertension" has been quite discouraging. This is indeed caused by the
      multifactorial nature of the disease and no improvement is to be expected without
      dissecting hypertension in its major pathogenetic pathways. As a paradigm of such
      a dissection, we present the data on adducin system, that proved to be relevant
      for a common form of salt sensitive in humans and the genetic hypertension of MHS
      rats.

PMID- 14696770
TI  - Mortality risk after hip fracture. 2003.

PMID- 14696771
TI  - Outcome after hip fracture in individuals ninety years of age and older. 2001.

PMID- 14696772
TI  - Femoral neck stress fractures and metabolic bone disease. 2001.

PMID- 14696773
TI  - Quality of life related to fracture displacement among elderly patients with
      femoral neck fractures treated with internal fixation. 2002.

PMID- 14696774
TI  - Circumstances of falls causing hip fractures in the elderly. 1998.

PMID- 14696775
TI  - Body mass and fracture risk: a study of 330 patients. 1999.

PMID- 14696776
TI  - Outcomes of elderly patients with nondisplaced femoral neck fractures. 2002.

PMID- 14696777
TI  - Percutaneous treatment of peritrochanteric fractures using the gamma nail. 2000.

PMID- 14696778
TI  - Use of the gamma nail in the treatment of fractures of the proximal femur. 1998.

PMID- 14696779
TI  - Second generation intramedullary nailing of subtrochanteric femur fractures: a
      biomechanical study of fracture site motion. 2002.

PMID- 14696780
TI  - Clinical characteristics and mycology of onychomycosis in autoimmune patients.
AB  - Onychomycosis is the most common nail disorder in adults. Predisposing factors
      are immunosuppression, poor peripheral circulation, diabetes mellitus, increasing
      age, nail trauma, and tinea pedis. Autoimmune patients, who carry many of these
      predisposing factors, have never been studied. Autoimmune patients, with
      underlying autoimmune skin diseases; pemphigus, systemic lupus erythematosus
      (SLE), mixed connective tissue disease (MCTD), scleroderma, dermatomyositis and
      cutaneous vasculitis, as well as having abnormal-appearing nail(s) with suspicion
      of fungal nail infection were included. Clinical information was obtained. The
      causative organisms were identified by potassium hydroxide preparation and
      cultured. Duration of onychomycosis in autoimmune patients was twice longer than
      in non-autoimmune patients. Of those with mycological proven onychomycosis, the
      autoimmune patients had significantly more affected nails (p < 0.05; chi2, two
      sided) compared to the non-autoimmune patients but there was no difference in the
      affected fingernails or toenails and clinical type of onychomycosis. Candida spp
      was the most frequently found in autoimmune subjects compared to dermatophytes,
      Trichophyton rubrum. However, dermatophytes especially Trichophyton rubrum was
      the most common causative organism in non-autoimmune samples, followed by Candida
      spp. The causative organisms were more frequently discovered in autoimmune
      patients, whether by potassium hydroxide (KOH) or culture, than in non-autoimmune
      patients (p < 0.05; chi2, two-sided).

PMID- 14696781
TI  - The prevalence and risk factors of anemia in pregnant women.
AB  - OBJECTIVE: To determine the prevalence and risk factors of anemia in pregnant
      women. METHOD: The pregnant women were screened with complete blood count,
      hemoglobin electrophoresis and serology tests for hepatitis B, syphilis and HIV.
      In cases of anemia, serum for iron and ferritin were investigated. Anemia was
      defined as a hemoglobin level less than 11.0 g/dl in the first and third
      trimester of pregnancy or less than 10.5 g/dl in the second trimester. Factors
      associated with anemia were analyzed by using student's t-test and chi-square.
      The statistically significant factors were tested with the use of multiple
      logistic regression. RESULTS: A total of 1,304 pregnant women were recruited. The
      prevalence of anemia was 19.2 per cent (251 cases). Classified in each trimester,
      the prevalence was 14.8 per cent, 20.5 per cent and 38.6 per cent in the first,
      second and third trimester, respectively. One hundred and sixty-one cases of
      anemia were available for serum iron and ferritin levels. Iron deficiency anemia,
      by means of serum ferritin, was detected in 32 cases (19.9%). An abnormal pattern
      of hemoglobin electrophoresis was detected in 367 cases (28.1%). Gestational age
      at first prenatal visit, abnormal hemoglobin electrophoresis and educational
      status were associated with anemia during pregnancy. CONCLUSION: The prevalence
      of anemia in pregnant women who first attended the prenatal visit was 19.2 per
      cent. Factors associated with anemia during pregnancy were gestational age at
      first prenatal visit, abnormal hemoglobin electrophoresis and educational status.

PMID- 14696782
TI  - Prevalence of rabies virus and Hantaan virus infections in commensal rodents and
      shrews trapped in Bangkok.
AB  - Five hundred rodents and shrews (Rattus norvegicus: 458, Rattus rattus: 28,
      Rattus exulans: 5, Mus musculus: 4 and Suncus murine: 5) trapped from the fresh
      food markets around Bangkok area were investigated for rabies virus and Hantaan
      virus infections. No rabies viral antigens in the animals' brains were detected
      by direct immunofluorescence. On the other hand, antibodies to Hantaan virus were
      demonstrated in the sera of 7 (1.53%) R. norvegicus caught in various markets
      using a particle agglutination technique. Further determination of the viral
      genome in rat lung tissue was performed by reverse transcriptase-polymerase chain
      reaction (RT-PCR) and nested PCR, 3 (0.66%) out of 7 were positive. HindIII and
      HifI restriction enzyme analyses showed the pattern of the Hantaan virus genome
      in 2 samples and that of the Seoul virus genome in the other. The results of the
      present study suggest that rodents from Bangkok's fresh food markets did not
      carry rabies. Thus, getting rid of rabies in dogs or cats in the Bangkok area may
      be easier than anticipated because there are no sources of asymptomatic
      reservoirs. This may result in the low incidence of rabies patients observed in
      Bangkok. On the contrary, the presence of antibodies and the Hantaan virus genome
      and Seoul virus genome in R. norvegicus will definitely provide evidence for
      physicians to be aware of hemorrhagic fever with renal syndrome (HFRS) and other
      clinical settings of Hantaan/Seoul virus disease in patients with a history of
      having contact with rats or their excreta.

PMID- 14696783
TI  - Quality of life of middle-aged female staff officers in the Royal Thai Navy Base,
      Bangkok.
AB  - OBJECTIVES: To assess the level of quality of life and to determine the factors
      associated with the quality of life of middle-aged female staff officers.
      MATERIAL AND METHOD: The population was 309 females aged 40-60 years who were
      working in the Royal Thai Navy Base in Bangkok, excluding those at the Naval
      Medical Department. Data collection was by self-administered questionnaires from
      June to July 2000. The t-test, one way analysis of variance, and Pearson's
      product moment correlation were used for data analysis. RESULTS: The majority of
      middle-aged female staff officers (61.8%) had overall scores which indicated that
      they had a moderate quality of life. The factors which were significantly
      associated with quality of life were marital status, menopausal symptoms, self
      esteem, social support, and family income. The factors which were not associated
      with quality of life were rank, age, educational level, number of living
      children, chronic diseases, stage of menopause and club membership. CONCLUSIONS:
      These results suggest that the responsible organizations should improve females'
      the self esteem of middle-aged female staff officers, establishing social
      networks and providing health promotion programs to enhance their well being, as
      well as quality of life.

PMID- 14696784
TI  - Midfacial degloving surgical approach: experience at Siriraj Hospital.
AB  - Midfacial degloving surgical approach is an excellent alternative to the lateral
      rhinotomy in exposure to the nasal cavity, paranasal sinuses and the nasopharynx.
      By lifting the soft tissue from the midportion of the face, many extensive benign
      tumors such as inverted papilloma, nasopharyngeal angiofibroma and some limited
      malignant lesions could be safely removed. This procedure could be combined with
      other approaches such as transtemporal, intracranial approach to resect more
      extensive tumors around the orbit, central skull base, as well. This technique
      was applied in 40 cases, ranging from 12-72 years of age and in a variety of
      diseases in Siriraj Hospital from 1991 to 2000. Fifty five per cent were
      diagnosed as inverted papilloma and 20 per cent were nasopharyngeal angiofibroma.
      The surgical technique in this operation was emphasized and it has proved to be
      an extensively valuable procedure for wide exposure of the operative field
      without any external scar. Functional outcome was obtained in most of the cases
      with minimal complications.

PMID- 14696785
TI  - The cost-effectiveness of a questionnaire as a screening test for chronic
      obstructive pulmonary disease among the Bangkok elderly.
AB  - This study aimed to explore the cost-effectiveness of using a questionnaire as a
      screening test for Chronic Obstructive Pulmonary Disease (COPD) among the Bangkok
      elderly residing around Siriraj Hospital. The gold standard used for diagnosing
      COPD followed the guidelines of the Thoracic Society of Thailand. The
      questionnaire consisted of 10 questions on smoking status, respiratory symptoms
      and previous history of pulmonary tuberculosis. There were 3,094 elderly who
      participated, completed the questionnaire, and underwent spirometry as well as
      chest radiography in the community. The results showed that elderly individuals
      who are smokers (> 0.5 pack-year) or have ever experienced sudden cough with
      chest oppression or dyspnea when the weather changes or who have expectorated
      more than two tablespoons of sputum would be suspected of having COPD with a
      sensitiviy of 81.4 per cent (95% CI 79.4-83.4), specificity of 62.2 per cent (95%
      CI 60.4-64.0) false negative rate 1.2 per cent (95% CI 0.7-1.7) and false
      positive rate 38 per cent (95% CI 35.3-40.7) and subsequently required spirometry
      and chest X-ray for definitive diagnosis. The test needed to screen 17 elderly
      individuals to detect one COPD case at a cost of 1,538 baht. This questionnaire
      is also a self-assessment tool for COPD screening among the elderly in order to
      encourage them to seek for early medical attention and it is recommended that
      this should be publicized via the mass media.

PMID- 14696786
TI  - The cost-effectiveness of chest radiography as a screening test for chronic
      obstructive pulmonary disease among the Bangkok elderly.
AB  - Regular screening with chest radiography (CXR) in an annual physical check up of
      the elderly is most frequently practiced. This study aimed to identify the CXR
      indices and the cost-effectiveness of CXR as a screening test for Chronic
      Obstructive Pulmonary Disease (COPD) among the elderly in 124 urban communities
      of Bangkok around Siriraj Hospital. The gold standard for diagnosing COPD
      followed the guidelines of the Thoracic Society of Thailand. There were 3,094
      subjects who participated, completed spirometry and a CXR. The selected nine
      indices from PA and lateral CXR for diagnosing COPD were based on the presence of
      hyperinflation. The positive criteria of each index were reported. The cut-off
      point of best average accuracy ie, Z score of the CXR was 0.07 with a sensitivity
      of 75.9 per cent (95% CI 70.2-81.6%), specificity of 72.4 per cent (95% CI 70.8
      74.0%) and the best average accuracy of 74.1 per cent (95% CI 72.5-75.7%) whereas
      the cost-effective cut-off point of a Z score of CXR as a screening test for COPD
      was 0.04 at the lowest grand total cost. The cost to detect one case of COPD was
      2,008 baht and needed to screen 17 elderly. It is suggested that CXR is probably
      not a suitable screening test for COPD in the elderly due to the complicated
      derivation of the CXR indices. However, its efficacy may be of some value in in
      office diagnosis of COPD.

PMID- 14696787
TI  - Botulinum toxin treatment for upper lid retraction of dysthyroidism.
AB  - Six patients with upper eyelid retraction due to dysthyroidism at Siriraj
      Hospital received subcutaneous botulinum toxin treatment at a dosage of 5-20
      units per injection. Five patients experienced an improvement in the lid
      retraction lasting at least 40 months and 3 patients required more than one
      injection. Botulinum toxin injection is an alternative treatment for the upper
      eyelid retraction of dysthyroidism, which is effective and causes minimal side
      effects, particularly in patients with euthyroid status.

PMID- 14696788
TI  - Collection and processing of umbilical cord blood for cryopreservation.
AB  - Umbilical cord blood (UCB) is being increasingly used as an alternative source of
      hematopoietic stem cells for allogeneic bone marrow transplantation. UCB
      transplantation has been successfully used to treat a variety of genetic,
      hematological, and oncological disorders in children and adults. The objectives
      of this study was to establish a closed-system technique for UCB collection and
      buffy coat separation by Optipress I device. Thirty-four UCB were collected by
      triple-bag system from pregnant mothers whose fetuses were not affected by
      thalassemic diseases after prenatal diagnosis. The mean volumn of UCB collection
      were 120 +/- 5 ml (range 65-180 ml). Total WBC, CD34+ cells, the progenitor cell
      erythroid burst-forming unit (BFU-E) and granulocyte-macrophage colony-forming
      unit (CFU-GM) in the UCB units were (9.36 +/- 0.84) x 10(8), (3.61 +/- 0.52) x
      10(6), (9.12 +/- 1.60) x 10(5), and (5.32 +/- 1.23) x 10(5), respectively. Good
      correlation between the nucleated cell and net cord blood volume could be
      demonstrated (p < 0.0001). The correlation between CD34+ cells and the following
      parameters: nucleated cell, BFU-E or CFU-GM were also demonstrated (p = 0.001,
      0.0105 or 0.0001, respectively). Buffy coat was subsequently separated from 18
      UCB units by Optipress I device. 70 +/- 3 ml of buffy coat were collected and
      cryoprocessing was done by automatic controlled-rate freezer. Good recovery of
      total WBC, CD34+ cells, progenitor cells BFU-E and CFU-GM after buffy coat
      separation were observed 89 per cent, 95 per cent, 109 per cent, and 102 per cent
      respectively. There was no aerobic bacterial or fungal contamination in the
      separated blood products. By using this technique, the UCB units were easily
      collected, rapidly separated within one hour, and high recovery of the
      hematopoietic progenitor cells could be obtained.

PMID- 14696790
TI  - Medical residency training in the US: important considerations.
AB  - The United States attracts medical scholars from abroad. However, the previously
      open-armed welcome extended to medical residents in America no longer exists for
      a variety of reasons. A series of barriers based on high educational standards
      and a rigid system of testing scientific and clinical skills and communication
      abilities, now tend to eliminate many applicants. Added to this is that American
      medical colleges now produce a near adequate number of new graduates and that
      foreign trained residents are often relegated to less desirable programs. These
      may not provide the level of training expected by the applicant. Less attractive
      programs are also less likely to enhance the scholar's chances of gaining an
      academic career and professional recognition on returning home. Applicants for
      residencies in the US should now be aware that only the best are likely to gain
      entrance to highly desired posts and to quality fellowships after completing a
      residency in America. All of this should be weighed against the stress and high
      costs that are now entailed in obtaining postgraduate medical training in
      America. This study endeavors to summarize what a young doctor should know about
      the application process for an American residency position and what he might
      expect from it.

PMID- 14696789
TI  - A bioequivalence study of the cefuroxime axetil in healthy volunteers.
AB  - The bioequivalence of 250-mg cefuroxime axetil was evaluated; Furoxime (by the
      Siam Bheasach Company, Thailand) as the test and Zinnat (GlaxoWellcome) as the
      reference. The two products were administered as a single dose according to a two
      way crossover design, 1-week washout period to 12 healthy Thai male volunteers.
      Thereafter, serial blood samples were collected over a period of 15 hours. Plasma
      cefuroxime concentrations were measured by HPLC. The pharmacokinetic parameters
      were analyzed by noncompartmental analysis. RESULTS: The Tmax [median (range, h)]
      of Furoxime and Zinnat were 1.5 (1.0-3.0) and 1.75 (1.0-3.5), respectively. The
      Tmax of Furoxime was faster than Zinnat with the mean (90% CI) of difference in
      Tmax of -0.5 [(-1.01)-0.01] h. Bioequivalence analysis showed that the AUC(0
      infinity) and the Cmax of the two products were not significantly different. The
      point estimator (90% CI) for the ratio [Furoxime/Zinnat] of log transformed data
      of the AUC(0-infinity) and Cmax were 1.03 (0.98-1.20) and 1.09 (1.02-1.24),
      respectively and were within the bioequivalence range of 0.80-1.25.

PMID- 14696791
TI  - Leiomyosarcoma in peripheral nerve: the first case report.
AB  - A neoplasm of the peripheral nerves can be obscured, especially during the early
      phase. The authors report a patient with sciatic nerve leiomyosarcoma. The
      patient's presentation and initial management are unique. A 51-year-old man with
      clinical manifestations of von Recklinghausen's disease reported numbness and
      weakness of the left leg for one and a half years. The symptoms gradually
      progressed. The symptoms were consistent with peripheral neuritis. The patient
      developed foot drop one month before coming to our service. Two episodes of
      biopsy confirmed leiomyosarcoma. A long, large sciatic nerve leiomyosarcoma was
      found intra-operatively, positioned from the upper thigh to the point where the
      tibial nerve passes beneath the upper margin of the soleus muscle. Surgical
      resection was done and confirmed the diagnosis. Decreased sensation was still
      intact after resection.

PMID- 14696792
TI  - Tracheal agenesis: a case report.
AB  - Tracheal agenesis is a rare congenital anomaly and typically has fatal
      consequences. Associated congenital malformations are present in 90 per cent of
      cases, most frequently affecting the cardiovascular or gastrointestinal systems
      and the genitourinary tract. Affected infants lack prenatal symptoms and usually
      present with severe respiratory distress, absence of audible crying and difficult
      or impossible endotracheal intubation, leading to failed airway management and
      irreversible cerebral hypoxia. The authors report an infant with tracheal
      agenesis who presented with respiratory failure after birth. The clinical
      features, embryology and classification schemes are presented in the hope of
      increasing awareness, thus making earlier diagnosis possible and thereby
      improving survival.

PMID- 14696793
TI  - Ethics and policy.

PMID- 14696794
TI  - Tropical pediatrics: 2002 to 2015.
AB  - It also presents the challenges that confront children in the tropics and their
      effects on the health of these children. These challenges include the technology
      divide, economic disparity, ecological changes, urbanization and
      industrialization, globalization, political instability, population explosion,
      and gender inequality. The paper paints a scenario of tropical pediatrics into
      the year 2015. Problems brought about by both underdevelopment and modernization,
      with urbanization and industrialization, will persist. Infectious diseases will
      continue to be the leading causes of deaths. The paper presents some significant
      achievements in the fight against tropical diseases and tries to predict what
      future progress will contribute to the alleviation of such diseases. The paper
      also outlines the commitment of the International Society of Tropical Pediatrics
      (ISTP) to improve the state of tropical pediatrics in the next 15 years.

PMID- 14696795
TI  - Molecular analysis of neurofibromatosis type 1 in Turkish families using
      polymorphic markers.
AB  - Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder
      characterized by multiple neurofibromas, cafe-au-lait spots, and Lisch nodules of
      iris. The NF1 gene is located on chromosome 17q11.2 and encodes an 11-13 kb mRNA
      containing 60 exons. The NF1 gene product neurofibromin is a large protein of
      2818 amino acids which acts as a negative regulator in the ras signal
      transduction pathway. The disease has a high mutation rate and a wide range of
      expression. Because of the size and complexity of the gene, the variety of
      mutations and the need to identify the specific mutation in each family, indirect
      diagnosis using linked markers has an important part in genetic counseling. We
      analyzed 10 Turkish families with a total of 28 affected individuals and 34 non
      affected relatives using polymorphic sequences, four intragenic and five flanking
      markers. Intragenic microsatellite markers were highly informative for all
      families. As a result, prenatal and presymptomatic diagnoses for familial cases
      are being made available.

PMID- 14696796
TI  - Analysis of the modifying effects of SAA1, SAA2 and TNF-alpha gene polymorphisms
      on development of amyloidosis in FMF patients.
AB  - The aim of this study was to examine whether polymorphisms at serum amyloid A
      (SAA) and tumor necrosis factor-alpha (TNF-alpha) genes are associated with
      development of amyloidosis in familial Mediterranean fever (FMF) patients.
      Seventy-three FMF patients with amyloidosis and 100 other FMF patients without
      amyloidosis of known genotypes and 100 healthy control subjects were analyzed.
      There was a significant difference in the frequency of alpha/alpha genotype at
      the SAA1 locus between FMF patients with amyloidosis and controls and FMF
      patients without amyloidosis. The frequencies of the alpha/alpha genotype and
      alpha alleles at SAA1 locus were significantly higher in the FMF patients with
      amyloidosis. The frequencies of the alpha allele at SAA1 locus in FMF patients
      with amyloidosis, without amyloidosis and controls were 85.6%, 49.5% and 42.5%,
      respectively. We demonstrated that alpha/alpha genotype at SAA1 gene might have
      modifying effects on the development of amyloidosis. Determination of genotypes
      at SAA1 locus can play a key role in conferring genetic susceptibility and
      patient's prognosis to renal amyloidosis.

PMID- 14696797
TI  - Impact of migration on Helicobacter pylori seroprevalence in the offspring of
      Turkish immigrants in Germany.
AB  - Helicobacter pylori (H. pylori) infection rates differ markedly between distinct
      populations. Consistent with previous findings of high seroprevalences in less
      developed countries, Turkish people have been reported to constitute a high-risk
      population. H. pylori prevalence rates have tended to be lower in Turkish
      individuals living in Germany for more than one generation. We conducted a
      seroepidemiological study to determine the impact of ethnicity, environmental
      setting, and sociodemographic factors on H. pylori seropositivity. Three
      subgroups were recruited encompassing 675 Germans (402 males, 273 females), 260
      Turkish people born and raised in Germany (145 males, 115 females) and 148
      Turkish people living in Turkey (91 males, 57 females), Ages ranged from newborn
      to a maximum of 30 years in all subgroups. H. pylori immunoglobulin G serum
      antibodies were determined by a commercial ELISA. H. pylori age-adjusted overall
      seroprevalence clearly differed between Germans (13.1%) and Turkish subgroups,
      with prevalences of 30.4% (Turks in Germany) and 44.5% (Turks in Turkey)
      seropositive individuals (p<0.001). Infection occurred at a younger age in Turks
      independent of country. Besides age, ethnicity was the only independent and
      significant predictor of H. pylori seropositivity using multiple logistic
      regression analysis (odds ratio 2.5; 1.3-5.0 95% confidence interval CI). Place
      of residence and number of children tended to influence H. pylori seroprevalence
      but without achieving statistical significance. Our data suggest that high H.
      pylori seroprevalence in Turkish people depends on factors that are only
      insignificantly influenced by migration. The causal environmental factors within
      this cohort and/or sociocultural practices that perpetuate and encourage the
      spread of infection remain to be identified.

PMID- 14696798
TI  - The results of electrophysiological study and radio-frequency catheter ablation
      in pediatric patients with tachyarrhythmia.
AB  - A total of 135 consecutive pediatric patients (pts) with tachyarrhythmia ranging
      from two to 21 years of age (median age 11 years) underwent electrophysiological
      study (EPS) between January 1994 and July 2001. Tachycardia could not be induced
      in 38 of 135 pts (28%) and studies in these patients were accepted as the normal
      EPS. Supraventricular tachyarrhythmia mechanisms were atrioventricular (AV)
      accessory pathways in 47 patients (manifest accessory pathways in 23 patients,
      concealed accessory pathways in 17 patients, permanent junctional reciprocating
      tachycardia in 7 patients), re-entry without accessory pathway in 26 patients (AV
      nodal reentry tachycardia in 20 patients, atrial flutter in 5 patients, sinus
      node re-entry tachycardia in 1 patient) and atrial ectopic tachycardia in eight
      patients. The diagnosis of ventricular tachycardia (VT) was made in 16 patients.
      Seventy-three of the 97 patients with the diagnosis of tachyarrhythmia as a
      result of EPS underwent radiofrequency (RF) catheter ablation. The indications,
      early results, complications, safety and efficacy of RF catheter ablation were
      reviewed in these patients. Among the 73 patients who underwent RF ablation (85
      procedures), the overall final success rate for all the diagnoses was 82% (60 of
      73 patients). The median follow-up period for all patients was 16 months (range 2
      to 60 months). Total recurrence rate in 73 patients was 4% (3 patients). Re
      ablation was performed in only one of them and was successful. Procedure-related
      complications occurred in eight patients (11%): transient third-degree AV block
      in one patient, transient second-degree AV block in one patient, atrial flutter
      in two patients (1 needed direct current cardioversion), and atrial fibrillation
      in three patients (2 needed defibrillation and transient pacemaker implantation).
      In one patient with permanent third-degree AV block a transvenous pacemaker
      implantation was required. These midterm results suggest that RF catheter
      ablation has a good success rate and a low complication rate in pediatric
      patients, especially when it is carried out in experienced pediatric cardiology
      centers.

PMID- 14696799
TI  - Congenital cardiac defects with 22q11 deletion.
AB  - New cytogenetic techniques have promoted progress in determining the role of
      chromosomal abnormalities in the cause of congenital cardiac defects. Some
      patients with congenital cardiac defect have a microdeletion within chromosomal
      region 22q11, and a majority of them are conotruncal cardiac defects. To
      determine frequency in our population, we evaluated 36 patients with congenital
      cardiac defects, 23 of them with conotruncal cardiac defects. Microdeletion of
      22q11 was detected in seven of 36 patients (19.4%), and in all deleted cases
      cardiac pathology was conotruncal.

PMID- 14696800
TI  - Clinical, electrophysiological and neuropsychological findings of twenty-two
      children with mesial temporal sclerosis.
AB  - Twenty-two patients, followed with the diagnosis of epilepsy between the ages of
      8.5 and 19 years who were found to have mesial temporal sclerosis (MTS) on brain
      magnetic resonance imaging (MRI) were evaluated according to their clinical,
      electrophysiological and neuropsychological characteristics, and assessed for the
      significance of neuropsychological tests on lateralization. In both MTS groups, a
      remarkable number of patients had their intial seizure before one year of age
      (45.5% in the right MTS group, and 36.4% in the left MTS group). Half of the
      patients were seizure-free for a period of two months-9.5 years (average 3.9
      years). The duration between the febrile seizure and first non-febrile seizure
      was 6.2 years. Eleven patients had MTS on the left temporal lobe. Interictal EEG
      was normal in five (22.5%) patients; 10 (45.5%) had temporal spike on the
      corresponding side with MTS. Six (27.3%) patients had paroxysmal activity and
      voltage asymmetry on cortical areas other than temporal region. The Wechsler
      Memory Scale (WMS), Visual Reproduction Subtest and Auditory Verbal Learning Test
      (AVLT) Delayed Recall and Retrieval Subtest performances were poor in the right
      MTS group.

PMID- 14696801
TI  - Association between early childhood caries and clinical, microbiological, oral
      hygiene and dietary variables in rural Turkish children.
AB  - Mutans streptococci are the principal bacteria isolated from children with early
      childhood caries (ECC). The aim of this study, therefore, was to determine the
      relationships between factors related to ECC with salivary mutans streptococci
      (MS). A total of 95 children with ECC from low-income families in rural Ankara
      participated in this study. Breast and/or bottle-feeding habits continued in
      31.5% of the children beyond 37 months. Forty percent of the bottle-fed, 35.5% of
      the breast-fed, and 29.4% of the breast-and bottle-fed children continued their
      habits beyond 37 months. Caries prevalence was significantly related to the age
      and feeding habits. Eighty one percent of the children did not have a
      toothbrushing habit and 41% had been taking sweetened medicine. High counts of MS
      are determined with increasing age, bottle usage, and snacking habits. We
      concluded that factors related to ECC are common among Turkish children.

PMID- 14696802
TI  - Clinical analysis of the trigger thumb of childhood.
AB  - Trigger thumb of childhood, termed congenital trigger thumb, is a pathology of
      the flexor pollicis longus tendon with an unknown etiology. In this study,
      treatment outcomes of 47 trigger thumbs of 36 children were evaluated. There were
      18 males and 18 females with a mean age of 34 months (9 months-13 years). Average
      age of recognition of pathology by the family was 20.5 months (0-8 years). In
      seven of 11 bilateral cases pathology was recognized simultaneously while in the
      other four, diagnosis was made at different times. We used conservative treatment
      for all patients under three years of age, which was unsuccessful. Thus, surgical
      relase was performed in all cases. In the mean follow-up of seven years (range 5
      15), contracture and palpable nodules disappeared. In conclusion, we believe
      trigger thumb in childhood should be treated surgically and that the term
      "congenital trigger thumb" should be changed to "developmental trigger thumb".

PMID- 14696803
TI  - Evaluation of bone with quantitative ultrasound in healthy Turkish children.
AB  - In this study bone status was assessed using a quantitative ultrasound (QUS)
      technique at the calcaneus in 141 healthy, prepubertal, Turkish schoolchildren
      (80 girls, 61 boys) aged 6-12 years. Broadband ultrasound attenuation (BUA,
      DB/MHz) was measured with a prototype pediatric contact bone analyzer (CUBA,
      McCue Ultrasonics Ltd). The relation of age, body weight and height to BUA was
      assessed. BUA increased linearly with age in boys and girls (R=0.448, p=0.0001
      and R=0.382, p=0.002, respectively). BUA values in boys tended to be higher than
      in girls, reaching significance only at the age of seven years with a 95%
      confidence interval. In conclusion, the measurement of BUA in the calcaneus with
      QUS has important clinical implications in assessing bone mass in children.
      Further studies in not only healthy children but also in those with metabolic
      bone diseases would be helpful in order to evaluate its sensitivity and
      reproducibility.

PMID- 14696804
TI  - Topical N-acetylcysteine treatment in neonatal ichthyosis.
AB  - Unpredictable trancutaneous absorption of topically administered drugs and
      potential teratogenicity and toxicity of systemic drugs would make it mandatory
      to innovate more efficacious and less toxic drugs for the treatment of
      ichthyosis, which is not a fully curable disease in the neonatal period. In this
      article the clinical efficacy of 10% N-acetylcysteine emulsion in the topical
      treatment of congenital ichthyosis in a newborn was assessed, comparing
      simultaneously with 4% urea emulsion. After treating the skin of the left and
      right halves of the body with topical N-acetylcysteine and 4% urea, respectively,
      for nine days, the improvement was much more outstanding on the skin of the left
      half of the body when compared to the right half of the body. Topical N
      acetylcysteine, to our knowledge, has not been used in a newborn with ichthyosis
      before, and this is the first report of a case of neonatal ichthyosis
      successfully treated with topical N-acetylcysteine. We conclude that 10% N
      acetylcysteine emulsion, as an non-toxic and hypoallergic amino acid derivative,
      can be safely and efficaciously used in the topical treatment of neonatal
      ichthyosis, although the permanent cure may not always be possible.

PMID- 14696805
TI  - Successful medical management of neutropenic enterocolitis (typhlitis) in a child
      with acute lymphoblastic leukemia.
AB  - We report a case of acute lymphoblastic leukemia that was complicated by
      neutropenic enterocolitis (typhlitis) during the initial period of remission
      induction chemotherapy. The patient's clinical symptoms resolved after aggressive
      treatment with intravenous fluids and electrolytes, nasogastric decompression,
      bowel rest, total parenteral nutrition, broad-spectrum antibiotics, and
      granulocyte colony-stimulating factor. Netropenic enterocolitis should always be
      considered in neutropenic leukemic children with the triad of fever, vomiting,
      and abdominal pain. Gastrointestinal hemorrhage may also accompany the symptoms
      described above. Plain roentgenogram, ultrasonography and computed tomography of
      the abdomen are helpful for making the diagnosis of this clinical condition.
      Early recognition and proper medical management of neutropenic enterocolitis may
      prevent the need for surgical intervention, and/or be life-saving.

PMID- 14696806
TI  - Childhood lichen planus with nail involvement: a case.
AB  - Childhood lichen planus is a very rare entity which is characterized by
      violaceous, scaly, flat-topped polygonal papules commonly involving the flexor
      aspects of the wrists and legs, and oral and genital mucous embranes. The
      incidence of lichen planus peaks between the ages of 30 and 60 years, where as
      children comprise only 2% to 3% of reported cases. We report a nine-year-old girl
      with widespread lichen planus, involving the nails, with no mucosal involvement
      and regressing after treatment with a starting dosage of 20 mg/day systemic
      flucortolon (Ultralan) therapy.

PMID- 14696807
TI  - Endobronchial tuberculosis complicated with Staphylococcus aureus pneumonia and
      empyema in a child.
AB  - Childhood tuberculosis might have unusual clinical presentation. A seven-year-old
      female patient was admitted with fever and pleural effusion. Her pneumonia
      resolved following 21-day treatment period. An atelectatic appearance remained on
      the right middle zone in her chest X-ray. Tuberculin skin test showed 13 mm
      induration. Triple drug antituberculosis treatment was started. Since atelectasis
      persisted on her follow-up radiograph one month later, bronchoscopy was performed
      which revealed a hemorrhagic polypoid mass occluding the right upper lobe
      anterior segment orifice. Surgical removal was performed by right upper
      lobectomy. The pathological diagnosis was necrotizing granulomatous infection
      suggesting tuberculosis. The patient has been well on follow-up after completing
      a nine-month course of antituberculous treatment.

PMID- 14696808
TI  - A rare cause of protein-losing enteropathy and growth retardation in infancy:
      infantile systemic hyalinosis.
AB  - Infantile systemic hyalinosis is a rare, progressive, fatal condition with a
      presumably autosomal recessive mode of inheritance. It is characterized by
      widespread deposition of hyaline material in many tissues. We present a three
      month-old girl with hypoproteinemia, growth retardation, and generalized stiff
      and edematous skin, who was diagnosed as protein-losing enteropathy. A final
      diagnosis of systemic hyalinosis was made. In this report, we present a very rare
      entity of infantile systemic hyalinosis, which is a cause of protein-losing
      enteropathy and growth retardation in infancy, and review the relevant
      literature.

PMID- 14696809
TI  - A case of hereditary angioedema with recurrent arthritis, erythema marginatum
      like rash and chest pain.
AB  - Hereditary angioedema (HAE) results from a congenital deficiency of C1 inhibitor
      and is characterized by submucosal and subcutaneous edema of skin, larynx and
      abdomen. Occasional reports have appeared linking HAE with autoimmune diseases.
      We report a case of HAE presenting recurrent nondeforming polyarthritis, erythema
      marginatum-like rash and chest pain. There were no significant radiographic joint
      changes. Serologic tests for rheumatologic and autoimmune diseases were negative.
      After danazol treatment, physical examination and laboratory findings were normal
      over five years. We suggest that pediatricians should be aware of this rare
      disease and treat patients accordingly.

PMID- 14696810
TI  - Congenital cutis laxa syndrome: type II autosomal recessive inheritance.
AB  - Cutis laxa is a term that refers to markedly loose skin that is not hyperelastic.
      It is regarded as a genetically heterogeneous group of diseases and is presently
      divided into five types. We report a male patient with type II autosomal
      recessive disease. The patient was the third child of first-cousin
      consanguineous, healthy parents. His two siblings died a few hours after birth.
      One of the siblings also had similar features and wrinkled skin. Our case had
      markedly loose and wrinkled skin especially over the dorsum of the hands and
      feet, and on the face and abdomen, dolichocephaly, hypertelorism,
      blepharochalasis, long filtrum, pectus excavatus, large fontanelles, prominent
      low-set ears and umbilical hernia. These findings and skin biopsy were consistent
      with cutis laxa syndrome. In addition to these findings, consanguinity, atypical
      facies, large fontanelles and umbilical hernia were typical manifestations of
      type II autosomal recessive cutis laxa.

PMID- 14696811
TI  - Persistent elevated serum levels of intact parathyroid hormone after reoperation
      for primary hyperparathyroidism and after pamidronate therapy.
AB  - Primary hyperparathyroidism is a life-threatening rare disorder. It is seen as a
      result of neonatal primary hyperparathyroidism, familial hypocalciuric
      hypercalcemia, increased vitamin D levels and inactivation of calcium sensing
      receptor mutations. The clinical findings are hypotonia, bone demineralization,
      hypercalcemia and parathyroid hyperplasia. We present a six-month-old female
      patient, the first child of nonconsanguineous parents, who was referred for the
      investigation of failure to thrive, vomiting, constipation, fever, abdominal
      distention and hypotonia. Physical examination revealed weight under 3rd
      percentile, height 3rd-10th percentile, decreased subcutaneous fat, and
      distention of the abdomen. In neurological examination, hypotonia, motor-mental
      retardation, and active deep tendon reflexes were found. The biochemical values
      at the time of admission revealed primary hyperparathyroidism. Since
      hypercalcemia did not respond to calcitonin therapy and due to the mortality of
      hypercalcemia, parathyroidectomy was performed. Because hyperparathyroidism and
      hypercalcemia continued, angiography was done which revealed increased
      parathyroid hormone levels in the periphery of the innominate vein. Exploratory
      surgery followed, but hyperparathyroidism and hypercalcemia persisted after all
      of these procedures. Calcium-sensing receptor mutations and supernumerary gland
      were considered. Because hypercalcemia persisted, pamidronate therapy was
      initiated on a monthly basis.

PMID- 14696812
TI  - Bardet-Biedl syndrome associated with vaginal atresia: a case report.
AB  - This is a case report of Bardet-Biedl syndrome associated with vaginal atresia
      diagnosed in a 15-year-old girl. She had mild mental retardation; obesity;
      nistagmus, retinitis pigmentosa and optic atrophy in both eyes; accessory digit
      on the left hand; polydactyly in lower extremities; a mobile, painful, nonfixed
      mass of 6 cm in diameter in the pelvic region; a palpable cystic mass in front of
      the rectal wall; and no vaginal opening. Secondary sex characteristics were
      determined. The vaginal atresia was distinguished from vaginal agenesis by the
      presence of proximal vagina in radiological examination.

PMID- 14696813
TI  - Sacrococcygeal extraspinal ependymoma: a case report.
AB  - Ependymomas, the common glial tumors of the spinal cord, occur occasionally
      outside the central nervous system and are called extraspinal ependymomas (ESE).
      ESE, which are clinically confused with other sacrococcygeal tumors, are rarely
      seen and found primarily in the sacrococcygeal region during childhood. We report
      a case of a seven-year-old boy presenting with a midline mass (6 cm diameter)
      over his coccyx. The solid mass was diagnosed as maxillopapillary type of
      ependymoma. Clinical and histopathological features of the case are described and
      literature reviewed.

PMID- 14696814
TI  - Treatment of visceral leishmaniasis.

PMID- 14696815
TI  - Prevention of hyponatraemia in children receiving fluid therapy.

PMID- 14696816
TI  - A road less travelled by. A review lecture given to the Royal Irish Academy on
      the occasion of the Award of Merit and Silver Medal by the Consultative Committee
      for Pharmacology & Toxicology on 22 November 2001.

PMID- 14696817
TI  - Self-administration of epinephrine in children: a survey of current prescription
      practice and recommendations for improvement.
AB  - The prevalence of peanut allergy is increasing rapidly and many children are now
      prescribed self-injectable epinephrine as part of their management. We aimed to
      examine the current extent of self-injectable epinephrine dispensing to children
      in the Eastern Health and Social Services Board (EHSSB), Northern Ireland,
      including indications for prescription, investigations performed, information and
      training provided and actual usage. Dispensing records held by the EHSSB were
      examined for the period May to August 1998. All general practitioners prescribing
      'Epipens' during this period were contacted and asked to identify the patient and
      provide contact details. Information was gathered using postal questionnaires
      sent to General Practitioners and parents. A total of 104 'Epipen' prescriptions
      were dispensed. Thirty-seven (36%) general practitioners responded to the initial
      questionnaire; of these 36 (35%) were suitable for analysis. Thirty-four parents
      were then contacted; 28 (82%) returned questionnaires were reviewed. The
      commonest indication for 'Epipen' prescription was peanut allergy (32 of 36 (89%)
      general practitioner responses; 25 of 28 (89%) parent responses). Twenty-six
      (72%) children had been seen by a specialist; all except one had either blood or
      skin tests. Six of the remaining eight children had no investigations. General
      practitioners reported 14 (39%) parents to have basic life support training,
      compared with six (21%) parents. Eighteen (64%) parents had been given written
      information regarding their child's allergy, nine (32%) had been referred to a
      dietician and seven (25%) children wore a medical warning bracelet. The Epipen
      had been used by three children; all three had multiple food allergies. This
      study has identified a great variability in the management of children with
      allergy including the need for specialist referral, further investigation,
      written allergy advice, referral to a dietician and formalised training in basic
      life support and administration of epinephrine. It suggests a lack of consensus
      amongst health care professionals as to the best practice in the management of
      potentially life threatening food allergy and indicates, at least, a need for
      better multidisciplinary communication.

PMID- 14696818
TI  - Impact of serum troponin measurement on triage of chest pain in a district
      hospital.
AB  - AIM: To evaluate the impact on the clinical service of incorporating cardiac
      troponin T (cTnT) measurement into the existing chest pain care pathway in our
      district general hospital. METHODS: We randomised 200 consecutive patients
      admitted with acute chest pain, but without ST elevation on ECG, either to our
      existing chest pain care pathway (pathway 1) or to a new pathway incorporating
      semi-quantitative cTnT measurement (pathway 2). RESULTS: In comparison with
      pathway 1, in pathway 2 there was a strong trend towards reduced length of stay
      (3.13 v 4.36 days, p=0.08), and reduced usage of low molecular weight heparin
      (LMWH) (4.59 v 5.45 doses per patient, p=0.05). The number of cardiac events at
      three months in care pathway 1 (14/92) and care pathway 2 (22/108) did not
      significantly differ, p=0.34. In patients with atypical chest pain, there was a
      tendency for cardiologists to discharge earlier (1.75 v 2.03 days, p=0.07) and
      use less LMWH (2.04 v 2.97 doses, p=0.06) than general physicians. CONCLUSION: In
      this study, incorporation of cTnT measurement into a chest pain care pathway
      resulted in a strong trend towards reduced length of hospital stay and LMWH
      usage.

PMID- 14696819
TI  - Ovarian cancer--the need for change in service delivery in Northern Ireland.
AB  - This paper provides local data on the provision of services for patients
      diagnosed with ovarian cancer in 1996 prior to the reorganisation of cancer
      services. It documents a service for 140 patients provided by 80 consultant teams
      and illustrates the need for reorganisation to meet the evidence base already in
      existence for improvement in survival and will serve as a baseline for future
      audits in this area.

PMID- 14696820
TI  - John Pemberton and the flax industry in Northern Ireland.

PMID- 14696821
TI  - Palliation of terminal malignancy with shape memory alloy ureteric stents.

PMID- 14696822
TI  - Infectious mononucleosis, ruptured spleen and Cullen's sign.

PMID- 14696823
TI  - Mycobacterium celatum pulmonary infection.

PMID- 14696824
TI  - Entero-cutaneous-vesical fistula: an unusual presentation.

PMID- 14696825
TI  - Gastric volvulus complicating cerebral palsy with kyphoscoliosis.

PMID- 14696826
TI  - Squamous cell carcinoma of the bladder and prostatic urethra in a post renal
      transplant patient.

PMID- 14696827
TI  - Acute osteomyelitis of the ilium mimics septic arthritis of the hip in children.

PMID- 14696828
TI  - Treatment of co-existing thoracic and abdominal aortic aneurysms using combined
      endoluminal stent grafts and conventional surgery.

PMID- 14696829
TI  - When nobody's looking.

PMID- 14696830
TI  - Protection of the public.

PMID- 14696831
TI  - Source of Black Death revisited.

PMID- 14696832
TI  - Cone beam volume tomography: a new digital imaging option for dentistry.

PMID- 14696833
TI  - 3-D volume imaging for dentistry: a new dimension.
AB  - The use of computed tomography for dental imaging procedures has increased
      recently. Use of CT for even seemingly routine diagnosis and treatment procedures
      suggests that the desire for 3-D imaging is more than a current trend but rather
      a shift toward a future of dimensional volume imaging. Recognizing this shift,
      several imaging manufacturers recently have developed 3-D imaging devices
      specifically for dental purposes using cone-beam computerized tomography. This
      technology allows for 3-D imaging similar to CT, but at lower equipment cost,
      simpler image acquisition and lower patient radiation dose. Herein, an overview
      of these devices is provided such that potential users can be better informed
      about this emerging technology.

PMID- 14696834
TI  - Cone beam CT for pre-surgical assessment of implant sites.
AB  - The pre-surgical assessment of proposed implant sites requires very specific and
      accurate data. Imaging has always been used to assist with the implant site
      assessment but until the recent introduction of cone beam CT scanners, the
      available imaging had a low value when considering the ratio between diagnostic
      potential, cost of study, and risk to the patient. CBCT scanners are nearing the
      end of their first-generation dedicated maxillofacial imaging modalities and have
      proven to be an extremely useful imaging tool for pre-surgical assessment of
      implant sites. CBCT scanners are easy to use and produce a 3-D image volume that
      can be reformatted using software for customized visualization of the anatomy.
      Protocols have been developed that optimize the visualization of image for
      implant site assessment.

PMID- 14696835
TI  - Management of impacted cuspids using 3-D volumetric imaging.
AB  - Management of impacted cuspids is a complex clinical problem involving proper
      assessment and interdisciplinary treatment planning. In this paper, we describe
      the use of 3-D volumetric imaging in the management of impacted cuspids and
      illustrate this application in case reports of maxillary and mandibular impacted
      cuspids.

PMID- 14696836
TI  - Newtom QR-DVT 9000 imaging used to confirm a clinical diagnosis of iatrogenic
      mandibular nerve paresthesia.
AB  - This article describes conventional orthodontic treatment of an adult patient
      leading to lower lip paresthesia. The paresthesia subsided when the cross
      elastics to correct the patient's single molar crossbite were removed. It was
      determined with Digital Volumetric Tomography that the inferior alveolar nerve
      was located lingual to the lower second molar root and was impinged upon with the
      tipping force of the cross elastic. Treatment to resolve the crossbite without
      further paresthesia is discussed.

PMID- 14696837
TI  - Cone beam volume tomography: an imaging option for diagnosis of complex
      mandibular third molar anatomical relationships.
AB  - Complex impacted third molars present potential treatment complications and
      possible patient morbidity. Objectives of diagnostic imaging are to facilitate
      diagnosis, decision making, and enhance treatment outcomes. As cases become more
      complex, advanced multiplane imaging methods allowing for a 3-D view are more
      likely to meet these objectives than traditional 2-D radiography. Until recently,
      advanced imaging options were somewhat limited to standard film tomography or
      medical CT, but development of cone beam volume tomography (CBVT) multiplane 3-D
      imaging systems specifically for dental use now provides an alternative imaging
      option. Two cases were utilized to compare the role of CBVT to these other
      imaging options and to illustrate how multiplane visualization can assist the
      pretreatment evaluation and decision-making process for complex impacted
      mandibular third molar cases.

PMID- 14696838
TI  - Nematodes worm their way back to the top.

PMID- 14696839
TI  - Industrial and agricultural pollution: a threat to the health of children living
      in the Arctic region.
AB  - Various environmental pollutants of industrial or agricultural origin such as
      persistent organic pollutants (POCs) are causing great concern owing to their
      toxicity to humans and animals. At the Stockholm Convention on POCs in 2001, 12
      of these pollutants, i.e. dioxins, PCBs (polychlorinated biphenyls) and DDT were
      referred to as "the dirty dozen". CONCLUSION: Collaborative studies by scientists
      from Canada, Russia, Scandinavia and other countries representing different
      fields such as environmental chemistry, ecology and medical sciences may increase
      our knowledge about the present threat of toxic chemicals to ecology and human
      health in the Arctic region. It is hoped that improved understanding will promote
      preventive political decisions.

PMID- 14696840
TI  - Adolescent-friendly services.
AB  - The time has come to discuss adolescent-friendly services and what these should
      entail. CONCLUSION: The attitudes and skills of the staff are the keys to
      successful healthcare for the adolescent. Communication skills include providing
      time without parental presence. Confidentiality in the patient-provider context
      is important but rules and practices vary from country to country and have to be
      learned. The United Nations Convention on the Rights of Children is a generic
      framework that makes a good starting-point. Ambiguous cases should be referred to
      groups of professionals and lay people trained in medical ethics.

PMID- 14696841
TI  - Why women don't breastfeed: a national survey.
AB  - Breastfeeding is a behaviour that is influenced by many complex factors and
      confounders. Various social and psychological factors may thus be missed in
      studies of the prevalence and duration of breastfeeding. The prevalence of
      breastfeeding is extremely high in the rich Scandinavian countries where the
      mothers are given paid maternity leave for at least one year. CONCLUSION:
      National and international women's organizations could improve the conditions for
      breastfeeding by pressing for a prolongation of the period of maternity leave
      worldwide.

PMID- 14696842
TI  - The respiratory pump: past and present understanding.
AB  - The history of our understanding of the respiratory system has been long and
      progressive, probably starting with Galenus who did experimental spinal cord
      sections, and progressed through the poorly known work of Leonardo da Vinci on
      the structure-function relation of chest wall components. CONCLUSION: Despite
      numerous experiments in the past, the respiratory control system remains complex
      and poorly integrated because of the diversity of the afferent pathways and of
      the interacting respiratory centres.

PMID- 14696843
TI  - Age differences in human skeletal muscle fatigue during high-intensity
      intermittent exercise.
AB  - It has been shown at similar relative work rates that children have higher
      resistance to fatigue than adults during repeated bouts of high-intensity
      exercise. This age-related difference in fatigue resistance may be explained by
      factors including muscle mass, muscle morphology, energy metabolism and
      neuromuscular activation. CONCLUSION: During high-intensity intermittent
      exercise, recovery periods play an important role in limiting fatigue. Age
      related differences in fatigue resistance could also be explained by differences
      in the rates of resynthesis of some energetic substrates and the rates of removal
      of various muscle metabolites.

PMID- 14696844
TI  - The importance of diet on exposure to and effects of persistent organic
      pollutants on human health in the Arctic.
AB  - AIM: To describe the importance of diet on exposure to and possible health
      effects of persistent organic pollutants (POPs) in the Arctic. METHODS: The study
      is based on a literature review. RESULTS: Minor decreases in POPs and minor
      increases in Hg levels in Arctic populations in Greenland, Eastern Russia,
      Western Alaska and Eastern Canada are likely to occur by the year 2010 and major
      decreases in both POPs and Hg levels in these same populations by 2030. Levels of
      POPs and metals in populations in the Faeroe Islands and the Scandinavian
      countries are already reasonably low and are only likely to decline marginally by
      2030. Estimating the effects on the basis of current knowledge is difficult, but
      the combination of improved methodology and selection of risk groups will be a
      progressive step in the process. Any strategies based on traditional food
      substitution should ensure that the value of the dietary components is sustained.
      CONCLUSIONS: To improve our understanding of the health effects associated with
      exposure to contaminants in the Arctic, we recommend that circumpolar
      epidemiological studies should be implemented on a larger scale. MeHg- and POPs
      related effects are still the key issues. However, the role of newly discovered
      contaminants, such as PBDEs (polybrominated diphenyl ethers) and PCNs
      (polychlorinated naphthalenes), should be investigated. For exposure assessment,
      mixtures and nutritional interactions should be considered in epidemiological
      studies. Epidemiological studies on nutritional benefits of traditional foods
      should be incorporated in risk-assessment profiles. We need a more nuanced view
      on human dietary exposure to xenobiotics. Risk should not be evaluated alone, but
      seen in relation to benefits from specific diets. It is essential that countries
      ratify and implement multinational environmental agreements.

PMID- 14696845
TI  - Association between serum oncofetal antigens CA 19-9 and CA 125 and clinical
      status in patients with cystic fibrosis.
AB  - In cystic fibrosis (CF), mucus plugging in the airways and in the
      gastrointestinal tract leads to severe morbidity and mortality. The mucin
      associated antigens CA 19-9 and CA 125 are markers of gastrointestinal
      malignancy, and CA 19-9 has also been reported in association with pulmonary
      function in CF. AIM: To test whether these antigens might serve as markers for
      the severity of pulmonary and gastrointestinal disease in CF. METHODS: In 99
      patients, aged 1 to 48 y, serum levels of CA 19-9 and CA 125 were measured by RIA
      and ELISA and related to clinical data. RESULTS: Patients with severe mutations
      had significantly increased serum levels of CA 125, indicating an association
      with a more severe CF phenotype. This was further supported by the association
      with lung function, chronic pulmonary colonization of Pseudomonas aeruginosa and
      pancreatic insufficiency. CA 19-9 was also shown to be associated with lung
      function and Ps. aeruginosa colonization. No gastrointestinal malignancy was
      found in our patients despite very high values of CA 19-9 in some patients.
      During a 5-y follow-up, the very high serum levels of CA 19-9 decreased along
      with improved general condition of the patients. CONCLUSION: Increased serum
      levels of CA 125 in CF patients were associated with severe cystic fibrosis
      transmembrane conductance regulator mutations and a severe phenotype. Both
      antigens were associated with pseudomonas colonization and lung function and CA
      125 also with pancreatic insufficiency. The estimates of CA 19-9 are hampered by
      the influence of the Lewis histo-blood group system on the synthesis of CA 19-9.

PMID- 14696846
TI  - Beta-glucuronidase in the diagnosis of bacterial meningitis and response to
      treatment.
AB  - AIM: Beta-glucuronidase activity is increased in the cerebrospinal fluid (CSF) of
      patients with bacterial meningitis. The aim of this study was to investigate the
      beta-glucuronidase activity in the cell-free CSF of bacterial meningitis and its
      course during treatment, and compare it with other CSF parameters. METHODS: The
      beta-glucuronidase activity, cell number, protein concentration and CSF/blood
      glucose ratio were measured in 43 consecutive infants and children with bacterial
      meningitis, and 97 control subjects. Patients had one or two follow-up lumbar
      punctures. RESULTS: The beta-glucuronidase activity was increased early in
      bacterial meningitis, even when the other CSF parameters were undisturbed. Before
      treatment, the median activity in affected children was 136 micromoles 4
      methylumbelliferone l(-1) h(-1) (range 44-826) and in controls 14 (7-23). In all
      patients who improved, the activity was lower in the follow-up CSF samples. Six
      to 12 h after starting treatment, the median activity was already reduced by 59%.
      The other CSF parameters showed a variability during the first 24 h of treatment
      independently of the course of the disease. Multiple comparisons of the CSF
      parameters in 17 patients who had two follow-up punctures showed that the beta
      glucuronidase activity was the best prognostic index. CONCLUSION: Beta
      glucuronidase activity in the CSF is a reliable indicator of bacterial
      meningitis, which can identify the response to treatment early in the course of
      illness. The enzyme activity is increased early in the disease, even when the
      other laboratory parameters from the CSF remain normal.

PMID- 14696847
TI  - Adhesion molecules, endogenous granulocyte colony-stimulating factor levels and
      replating capacity of progenitors in autoimmune neutropenia of childhood.
AB  - AIM: To investigate the role of granulocyte colony-stimulating factor (G-CSF) and
      adhesion molecules and the response of bone marrow to peripheral cytopenia in
      autoimmune neutropenia of childhood (AIN). METHODS: Thirty-five children with
      AIN, 25 with acute leukaemia in remission, 10 of whom developed chemotherapy
      associated neutropenia, and 28 non-neutropenic age-matched children were studied.
      The methods included haemopoietic progenitor cells' colony growth, replating of
      colony-forming unit-granulocyte macrophage (CFU-GM) of the 7th day and ELISA for
      the detection of serum levels of cytokines and adhesion molecules. RESULTS: In
      cases of severe autoimmune neutropenia, haemopoietic progenitors showed increased
      proliferative capacity compared to the control group (p = 0.03). Intercellular
      adhesion molecule-1 (ICAM-1), E-selectin, tumour necrosis factor-alpha (TNF
      alpha) and interleukin-1beta (IL-1beta) levels inversely correlated with
      neutrophil counts (r = -0.8, p < 0.001 for ICAM-1, r = -0.5, p = 0.04 for E
      selectin, r = -0.58, p = 0.01 for TNF-alpha, r = -0.62, p = 0.04 for IL-1beta).
      Serum ICAM-1, TNF-alpha and IL-1beta levels correlated positively with G-CSF
      levels (r = 0.47, p = 0.03 for ICAM-1, r = 0.65, p = 0.01 for TNF-alpha, r =
      0.67, p = 0.04 for IL-1beta). Serum G-CSF levels were widely distributed and did
      not correlate with neutrophil counts (r = -0.44, p = 0.09). In secondary
      neutropenias the respective levels were lower than those in autoimmune
      neutropenia. CONCLUSIONS: Haemopoietic progenitors show increased proliferative
      capacity in cases of severe autoimmune neutropenia. G-CSF seems to act as an
      inducer of endothelium activation. The degree of neutropenia correlates with
      serum ICAM-1, E-selectin, TNF-alpha and IL-1beta levels, indicating the existence
      of an activated endothelium and presumably of a latent, low-grade, inflammatory
      process in severe autoimmune neutropenia.

PMID- 14696848
TI  - Serum thyroglobulin as a marker of thyroid neoplasms after childhood cancer.
AB  - AIM: To evaluate serum thyroglobulin (Tg) level as a marker of the development of
      thyroid disease when following individuals who received neck irradiation therapy
      in childhood. METHODS: In a non-randomized cross-sectional study Tg was assessed
      in 172 survivors of childhood cancer 10.8 y (1.9-24) median (range) after
      diagnosis and 7.9 y (0.9-24.3) median (range) after the end of treatment. The
      patients were divided into two groups: group 1 included 47 patients who had
      received irradiation to the neck and group 2 included 125 patients who did not
      receive irradiation to the neck. RESULTS: Patients who had received irradiation
      to the neck had significantly higher Tg levels compared with those who did not
      receive neck irradiation: median 14.0 (1.0-189.0) microg/L vs median 8.8, (0.7
      112.2) microg/L (p < 0.001). Six out of seven patients with elevated Tg levels
      (>70 microg/L) had received neck irradiation. Among these six patients, two
      patients developed secondary differentiated thyroid cancer and two patients
      developed benign thyroid neoplasms. None of the patients who had normal levels of
      Tg developed thyroid cancer. CONCLUSION: A high Tg level should be a cause for
      further investigation in the follow-up of individuals who have received
      irradiation therapy in childhood.

PMID- 14696849
TI  - Hand strength in juvenile chronic arthritis: a two-year follow-up.
AB  - AIM: To describe changes in muscle strength in the hands of children with
      juvenile chronic arthritis (JCA) and to examine the relationship between muscle
      strength, presence of local arthritis and disease subtype. METHODS: Twenty
      children (10 girls and 10 boys) with JCA aged 7 to 18 y were followed for two
      years. Isometric muscle strength in wrist dorsiflexors and handgrip strength were
      measured repeatedly. The results were compared with reference values for the same
      methods. Arthritis severity in the hand was scored every third month. Nerve
      conduction velocities were measured twice. RESULTS: Seven out of 20 patients had
      initially low or decreasing strength in one or both of the two tests. Five out of
      20 children had reduced strength (more than two standard deviations below the
      mean of the reference group) in at least one test. Four children showed a
      significant reduction in muscle strength in at least one test during the
      observation time. The greatest reduction in strength was measured in four
      children with polyarticular disease. These children also had local arthritis in
      the hand. A greater proportion of children with polyarthritis had low or
      decreasing strength compared with children with oligoarthritis. The same was true
      for children with active arthritis in the hand. Nerve conduction velocities were
      normal in all cases and did not change. CONCLUSION: The majority of children with
      JCA have normal strength in the hand. Some children, especially those with
      polyarthritis and hand arthritis, have reduced muscle strength in the hand. Risk
      factors for low or decreasing strength are polyarthritis and/or active arthritis
      in the hand.

PMID- 14696850
TI  - Laryngeal and diaphragmatic muscle activities after central nervous system
      lesions in cats.
AB  - AIM: To examine the central control and coordination of respiratory pump muscles
      and laryngeal valve muscles by systematic decerebration (DECER), cerebellectomy
      (CBELL), pontine respiratory group lesioning (PRG) and pontomedullary section
      (PMED). METHODS: Activities of posterior cricoarytenoid (PCA), thyroarytenoid
      (TA) and diaphragm (D) muscles and their responses to inspiratory (I) and
      expiratory (E) total occlusions were determined in 10 adult cats. RESULTS: INTACT
      anesthetized cats (n = 6) exhibited inspiratory PCA (PCA(I)) and D activities.
      Expiratory PCA (PCA(E)) was present but TA activity was absent. It was found that
      successive DECER, CBELL and PRG lesions attenuated PCA(E), the intact pattern
      being noted in 7/10, 4/10 and 0/6 cats, respectively. After PMED, variable PCA,
      TA and continuous D activities occurred only with blood gas abnormalities.
      Augmented PCA and D responses to I- and E-loads occurred after PRG lesions: the I
      load PCA(I) and D responses resembled apneusis and the E-load PCA(E) and D
      responses resembled central apnea. CONCLUSION: The decreasing PCA(E) activity
      observed with successive DECER, CBELL and PRG lesions suggests that these areas
      influence laryngeal abductor control of glottic size. The synchronous activities
      after PMED transection suggest a role for more rostral structures in coordinating
      laryngeal and diaphragmatic muscle activities.

PMID- 14696851
TI  - Why primiparous mothers do not breastfeed in the United States: a national
      survey.
AB  - AIM: To investigate primiparous women's primary reason for not breastfeeding.
      METHODS: We used the 1995 National Survey of Family Growth to analyze the
      breastfeeding behaviors of a national probability sample of 6733 first-time US
      mothers, aged 15 to 44 y. Main outcome measures in this cross-sectional study
      were the reasons for never breastfeeding and reasons for stopping breastfeeding
      using closed-ended, multiple choice questions. RESULTS: Most commonly, women did
      not breastfeed because they "preferred to bottle feed" (66.3%). The most common
      reason for stopping breastfeeding was that the child was "old enough to wean"
      (35.7%), although 15%, 34%, 54%, and 78% of those women had stopped breastfeeding
      by 3, 6, 9, and 12 mo, respectively. "Physical or medical problem" was reported
      by 14.9% of women who did not breastfeed and 26.9% of women who had stopped
      breastfeeding, making it the second most common reason for not breastfeeding in
      each group. There were significant differences across racial and ethnic groups.
      CONCLUSION: Additional studies are needed to better understand why women "prefer
      to bottle feed", especially black women. Increasingly effective programs and
      policies to promote breastfeeding will logically follow. Since physical and
      medical problems are such common reasons both for never breastfeeding and for
      stopping breastfeeding, individual healthcare providers can have a significant
      impact on breastfeeding rates and duration.

PMID- 14696852
TI  - Respiratory syncytial virus infection--risk factors for hospital admission: a
      case-control study.
AB  - Most infants are infected with respiratory syncytial virus (RSV) during the first
      2 y of life. The majority have only a mild upper respiratory tract infection, but
      1-2% develop a more severe illness and are admitted to hospital. AIM: To carry
      out a study of risk factors for hospital admission because of RSV infection in
      Denmark in children aged less than 2 y of age. METHODS: The study population
      included all 1252 children admitted to hospital with verified RSV infection in
      two Danish counties during the 5-y period 1990-1994. The investigation comprised
      a retrospective case-control study with five matched controls per case. In a
      multivariate analysis the risk factors included medical and demographic
      variables, and in infants <3 mo of age at hospitalization, two aspects of innate
      immunity: mannose-binding lectin (MBL) concentration and maternal RSV serum
      antibody titre, measured on eluates from stored dried blood from the infants' 4th
      day of life. The effect of each risk factor is expressed as an odds ratio,
      corresponding to the relative risk of being a case rather than a control if the
      risk factor is present. RESULTS: The following independent risk factors were
      identified: age, sex, month of birth, gestational age, birthweight, presence of a
      sibling, up to 5 y older than the case, and maternal smoking during pregnancy.
      There was a marginal effect of maternal RSV antibody levels, but no effect of
      neonatal serum MBL concentration or of crowding in the household. CONCLUSIONS:
      Ninety percent of cases and 80% of controls had one or more risk factors. Even
      though several factors were found to increase the risk for hospitalization for
      RSV disease, all the effects were small and no single specific factor could be
      identified to explain the hospitalization of the minority of children with RSV
      infection.

PMID- 14696854
TI  - Total energy expenditure, body composition and weight gain in moderately preterm
      and full-term infants at term postconceptional age.
AB  - AIM: To assess total energy expenditure (TEE) and body composition, i.e. total
      body water (TBW) and adipose tissue volume (ATV), at term age in 8 healthy
      preterm infants, born between gestational weeks 30 and 33, and in 9 healthy full
      term newborns. METHODS: Total and subcutaneous ATVs were assessed using magnetic
      resonance imaging, while TEE and TBW were estimated using doubly labelled water.
      RESULTS: Total ATV was 272 +/- 21 and 261 +/- 56 ml/kg body weight, while
      subcutaneous ATV was 88.9 +/- 1.6 and 89.7 +/- 2.0% of total ATV for preterm and
      full-term infants, respectively. The corresponding figures for TBW (as percentage
      of body weight) were 67.4 +/- 2.5 and 68.1 +/- 4.1, respectively. A significant
      correlation between ATV/kg body weight and body weight was found for full-term (p
      < 0.0001) but not for preterm infants. TEE for preterm infants was 315 +/- 20
      kJ/kg body weight/24 h, which was significantly higher (p < 0.05) than TEE for
      full-term infants (254 +/- 45 kJ/kg body weight/24 h). At the time of
      investigation preterm infants weighed significantly (p < 0.05) less (540 g) than
      full-term infants. After the time of investigation, weight gains of preterm and
      full-term infants were 38 +/- 12 and 24 +/- 14 g/24 h, respectively. CONCLUSION:
      When compared to full-term newborns, predominantly breastfed healthy preterm
      infants at term postconceptional age were significantly smaller, had a similar
      average proportion of body fat and showed catch-up growth. Their higher TEE/kg
      body weight can be explained by a higher growth rate and possibly also by higher
      physical activity.

PMID- 14696853
TI  - Consultations with adolescents: the gap between their expectations and their
      experiences.
AB  - AIM: To study the expectations and experiences of adolescents when in
      consultation with doctors, particularly with regard to issues of confidentiality.
      METHODS: In a cross-sectional study, 613 seventh- and ninth-grade students (347
      students aged 13 y and 266 students aged 15 y) completed a 40-item questionnaire
      specifically developed for this study. Students anonymously completed the self
      administered questionnaire at school. RESULTS: Of these adolescents, 89% aged 13
      y and 57% aged 15 y were accompanied by one of their parents to appointments with
      private practitioners. Of the respondents, 33%/52% (13-y-olds/15-y-olds) said
      that seeing the doctor alone for some time was important but only 18%/20% were
      given the opportunity to do so. Although 79%/90% of respondents stated that it
      was important for the doctor to keep information confidential, on request, only
      37%/40% of private practitioners had spoken about confidentiality; 64%/78% of
      adolescents said that doctors should give assurance of confidentiality even with
      regard to their parents. However, only 26%/27% of private practitioners
      explicitly assured confidentiality with regard to parents. Acceptance of
      conditional confidentiality was high in all subpopulations. Short waiting times
      and the opportunity to talk about topics such as nutrition, drugs and sexuality
      were rated as important. CONCLUSION: Physicians should adapt their consultation
      style to the needs of adolescents by seeing the adolescent patient alone for some
      time and by assuring them of conditional confidentiality. Furthermore, they
      should provide opportunities to talk specifically about issues of potential
      concern to adolescents such as nutrition, drugs and sexuality. To accomplish
      these tasks, educational curricula in adolescent healthcare are required for
      physicians.

PMID- 14696855
TI  - Preterm delivery and calculation of survival rate below 28 weeks of gestation.
AB  - AIM: To estimate the number of still- and live-births below 28 wk of gestation in
      a 2-y period in Denmark, and to determine how the calculated survival rates vary
      using three different denominators: 1) the number of infants actively treated in
      the Neonatal Care Units, NNUs, 2) the number of all live-born infants, and 3) the
      number of all births, including stillbirths. METHODS: The number of stillbirths
      and live-born infants at 20 to 27 wk of gestation was estimated over a 2-y period
      in Denmark. Data on live-born infants and survival rates were obtained from a
      national prospective study and the National Births Register. The number of women
      hospitalized owing to spontaneous abortion was obtained from The Danish National
      Health Register; the number of stillbirths was calculated from these data.
      RESULTS: The estimated number of both still- and live-births was similar in every
      week from 20 to 27 wk of gestation; approximately 1 per 1000 live-births at each
      gestational week. At from 23 to 25 wk of gestation the overall chances of
      survival varied significantly depending on the denominator: actively treated
      infants 46% (CI 95%; 37%-54%), all live-born infants 34% (CI 95%; 27%-41%), all
      births including stillbirths 14% (CI 95%: 11-17%). CONCLUSION: The chances of
      survival for the intrauterine fetus below 26 wk of gestation are significantly
      lower than the reported survival rates from the NNUs. The low percentage of
      fetuses delivered before 26 wk of gestation classified as live-born renders the
      reported birth-rates sensitive to differences in the way "live-born" is
      interpreted.

PMID- 14696856
TI  - Syncope in a child owing to intramural course of the left coronary artery.
AB  - Coronary abnormalities are a rare cause of syncope or sudden death in childhood
      or adolescence. We report on a 14-y-old girl who had suffered for many years from
      repeated syncope after or during exertion. She had to be resuscitated twice. The
      left coronary artery arose from the right coronary aortic sinus and took a
      proximal intramural course. After successful reimplantation, the patient has now
      been free of symptoms for 12 mo. The pitfalls of differential diagnosis of this
      rare anomaly are discussed. CONCLUSION: Investigation of the coronary anatomy is
      indicated in otherwise unexplained chest pain, syncope or life-threatening
      events.

PMID- 14696857
TI  - Mother-to-child transmission of HIV: developing integration of healthcare
      programmes with clinical, social and basic research studies. Report of the
      International Workshop held at Chobe Marina Lodge, Kasane, Botswana, 21-25
      January 2003.
AB  - Considerable efforts are still needed in the public health sector, as well as in
      clinical, social and basic research, to improve programmes for HIV-1 MTCT (mother
      to-child transmission) prevention and care. Advantage should be taken of the
      remarkable amount of expertise and resources that have accumulated over the past
      few years to accelerate the process of integration. Future initiatives should
      include integrating specialists and people with diverse backgrounds and targeting
      their scientific and programmatic ideas to address real-world problems in the
      area of MTCT of HIV-1.

PMID- 14696858
TI  - Do sensational media reports about severe acute respiratory syndrome affect the
      mindset of healthcare workers?

PMID- 14696859
TI  - VACTEL association at autopsy of a foetus.

PMID- 14696860
TI  - Fetal bradycardia at 28 weeks of gestation associated with cardiac glycogen
      phosphorylase b kinase deficiency.

PMID- 14696861
TI  - Recombinant human erythropoietin might induce strawberry haemangiomas in very-low
      birthweight preterm infants.

PMID- 14696862
TI  - The predominance of omega-6 polyunsaturated fatty acids in cystic fibrosis
      despite low arachidonic acid levels.

PMID- 14696863
TI  - Association between polymorphism of interleukin-1beta-511 promoter and
      susceptibility to febrile convulsions in Taiwanese children.

PMID- 14696864
TI  - Two cases of Salla disease in Danish children.

PMID- 14696865
TI  - Will advances in biotechnology usher in a new era of medicine?

PMID- 14696866
TI  - Stress and the obstetrician.

PMID- 14696867
TI  - Patient perception of physician appearance: a concern for all physicians.

PMID- 14696868
TI  - Biotechnology and drug discovery: from bench to bedside.
AB  - New biotechnology and drug discovery technologies are facilitating the rapid
      expansion of the clinical drug chest, empowering clinicians with a better
      understanding of disease as well as novel modalities for treating patients.
      Important research tools and themes include genomics, proteomics, ligand-receptor
      interaction, signal transduction, rational drug design, biochips, and
      microarrays. Emerging drug classes include monoclonal antibodies, cancer
      vaccines, gene therapy, antisense strands, enzymes, and proteins. In this
      article, we review these topics and illustrate their potential impact by
      presenting an overview of promising drugs in the pipeline. Clinicians who use
      these novel treatments must become familiar with these trends.

PMID- 14696869
TI  - Occupational stress among obstetrician/gynecologists.
AB  - OBJECTIVE: Our objective was to assess occupational stress in
      obstetrician/gynecologists using a standardized, validated tool. METHODS: The
      Osipow Occupational Stress Inventory, which measures occupational stress
      (occupational roles questionnaire [ORQ]), psychological strain (personal strain
      questionnaire), and coping resources (personal resources questionnaire), was
      distributed to 277 obstetrician/gynecologists in Houston. The chi2 or Fisher's
      exact test was used where appropriate. RESULTS: Sixty-nine surveys were analyzed.
      Median T scores for all subscales were within the normal range. Abnormal scores
      were recorded by 22 physicians (31%) on at least one subscale of the ORQ, by 5
      physicians (7%) on at least one subscale of the personal strain questionnaire,
      and by 6 physicians (9%) on at least one subscale of the personal resources
      questionnaire (P < 0.05). Abnormal scores occurred more frequently in the ORQ
      domain. Generalists had significantly more abnormal scores than did
      subspecialists (P < 0.05). CONCLUSION: Occupational stress is common among
      obstetrician/gynecologists. This appears to be balanced by good coping skills.

PMID- 14696870
TI  - Patients' attitudes regarding physical characteristics of family practice
      physicians.
AB  - BACKGROUND: This study examined patient perceptions and attitudes toward various
      aspects of the male and female physician's professional appearance in the family
      practice setting. METHODS: Four hundred ninety-six patients from two family
      practice clinics in Knoxville, Tennessee, completed a valid and reliable
      questionnaire. Questionnaires were offered to all patients on registering at
      their respective clinic during a 2-week period. RESULTS: Most patients had no
      preference regarding the age or sex of their medical care provider. A nametag,
      white coat, and visible stethoscope were the most desirable characteristics,
      whereas sandals, clogs, and tennis shoes were the least desirable items. Younger
      patients were generally more accepting of casual attire than were older patients.
      Office clinic location was the most important predictor of preferences in six of
      the significant characteristics. CONCLUSION: Our findings support the results of
      both studies published two decades earlier and more recently. Patients prefer a
      traditionally dressed physician as opposed to one who is dressed more casually.

PMID- 14696871
TI  - The impact of resident physician coverage on emergency department visits in South
      Carolina.
AB  - BACKGROUND: This study examines emergency department (ED) visits to assess the
      potential impact on rural and minority patients if the practice of resident
      moonlighting was limited. METHODS: Billing data from all South Carolina ED visits
      in 1998 were linked to the physician licensure file. Logistic regression analysis
      was performed to determine patient characteristics predictive of being seen by a
      resident physician. RESULTS: Resident physicians attended 3.4% of visits for
      patients residing in rural areas and 1.4% of those from urban areas. The odds of
      being treated by a resident were higher among persons living in health
      professional shortage-designated or rural areas, minorities, and persons with
      government insurance. CONCLUSION: Patients from vulnerable populations have
      greater odds of being seen by a resident physician for an ED visit. These
      populations may be placed at risk for reduced access to health care services if
      limitations on resident physician moonlighting impair the ability of rural
      hospitals to staff EDs.

PMID- 14696872
TI  - Agricultural tasks and injuries among Kentucky farm children: results of the Farm
      Family Health and Hazard Surveillance Project.
AB  - BACKGROUND: This population-based study reports the prevalent agricultural tasks
      and the 1-year cumulative incidence of injuries in a sample of 999 children < or
      = 18 years old living on family farms in Kentucky. METHODS: Data were collected
      in 1994 to 1995 for the National Institute for Occupational Safety and Health
      Farm Family Health and Hazard Surveillance Project. A random sample of farm
      children in 60 Kentucky counties was selected using a cross-sectional, two-stage
      cluster design. Respondents, primarily mothers, completed a 30-minute telephone
      interview about work-related tasks and injuries experienced by their children
      while working on the farm. RESULTS: Participation in chores related to tobacco
      and beef cattle production was common for children aged 5 to 18 years. In a 1
      year period, 29 children were injured while performing farm work, yielding a
      crude rate of 2.8 per 100 children (95% confidence interval, 1.7-3.8). Boys aged
      16 to 18 years had the highest injury rate (9.2 per 100 children). Farm
      machinery, cattle and horses, falls from heights, and contact with inanimate
      objects were the primary external causes of nonfatal farm work injuries.
      CONCLUSION: Rates of farm work injuries among adolescent boys may be higher than
      previously reported for Kentucky and other states. Injury prevention
      interventions targeted to chores related to tobacco and beef cattle production
      are particularly relevant for this population of young workers.

PMID- 14696874
TI  - The Confederate medical laboratories.
AB  - During the Civil War, the scarcity and expense of imported drugs forced the
      Confederate Army to establish several medical laboratories to manufacture drugs
      for military use. The laboratories produced medicines from indigenous plants and
      also made non-plant-based drugs. The Confederate Surgeon General and the Chief
      Purveyor in Richmond, VA, coordinated activities of most of the laboratories. The
      laboratories employed talented and resourceful personnel and manufactured a large
      volume and wide variety of drugs, the most useful of which included ether,
      chloroform, and opiates. The pharmaceutical quality of the laboratories' output
      was evidently uneven. Empirical testing in military hospitals helped determine
      the clinical value of indigenous remedies. The Confederate medical laboratories
      participated in a coordinated effort to supply the Army with substitutes for
      drugs whose availability was curtailed or uncertain.

PMID- 14696873
TI  - Work-related injury among south Texas middle school students: prevalence and
      patterns.
AB  - BACKGROUND: Work experiences among early adolescents are largely undocumented.
      Our purpose was to document the prevalence of work and work-related injury among
      lower-income Hispanic South Texas middle school students. METHODS: Anonymous
      surveys were conducted in classrooms of sixth- through eighth-grade students, and
      3,008 students reported current or recent employment. RESULTS: The prevalence of
      work was 56%; mean weekly work hours were 7.7. Increasing weekly work hours were
      significantly related to work injury (11-20 hours, odds ratio [OR], 1.5; 95%
      confidence interval [CI], 1.1-1.9; 21+ hours, OR, 2.4; 95% CI, 1.8-3.2, compared
      with 1-10 hours). The odds of injury were highest for agriculture (OR, 4.4; 95%
      CI, 3.3-6.0), followed by restaurant (OR, 3.8; 95% CI, 2.7-5.4), construction
      (OR, 3.6; 95% CI, 2.4-5.2), and yard work (OR, 1.7; 95% CI, 1.4-2.2). CONCLUSION:
      Working more than 20 hours weekly increased the likelihood of injury among middle
      school students. Parents and professionals should monitor weekly school-year work
      hours.

PMID- 14696875
TI  - Use of birth certificates and surveillance data to characterize reported
      pertussis among Texas infants and young children, 1995 to 2000.
AB  - BACKGROUND: Pertussis morbidity is increasing, especially among young infants and
      children, who are more likely to be hospitalized and have more severe
      complications. Maternal and pediatric factors associated with underimmunization
      and hospitalization for pertussis are poorly understood, but young maternal age
      and low birth weight have been associated with pertussis among young infants.
      METHODS: We used pertussis surveillance data, matching cases to the birth
      certificates of 416 Texas infants and children reported as pertussis cases during
      1995 to 2000. Maternal/pediatric information gathered from birth certificates
      included birth weight, gestational age, and maternal factors (age, birthplace and
      education level, prenatal care, and previous live births). We assessed the
      immunization status of the cases and maternal/pediatric factors associated with
      underimmunization with a pertussis-containing vaccine and hospitalization using
      descriptive statistics and logistic regression. RESULTS: The 416 cases
      represented 20% of the pertussis morbidity in Texas from 1995 through 2000. Most
      children had not been vaccinated (275 [66%]), even though 374 (90%) were old
      enough for at least one dose. Among those 374 children, only those younger than 6
      months were associated with underimmunization (odds ratio [OR], 9.98; 95%
      confidence interval [CI], 6.24-15.97). Most patients (253 [61%]) were
      hospitalized. Hospitalization was associated with complications of apnea (OR,
      2.13; 95% CI, 1.39 2.38), pneumonia (OR, 5.26; 95% CI, 2.94-11.59), and age
      younger than 6 months (OR, 2.11; 95% CI, 1.38-3.23). CONCLUSION: More than two
      thirds of the children reported as pertussis cases were old enough to have at
      least one dose of a pertussis-containing vaccine but were not immunized. Maternal
      and pediatric characteristics on birth certificates were not useful in predicting
      either underimmunization or hospitalization for pertussis complications. More
      current assessments of maternal and pediatric characteristics should be part of
      pertussis contact investigations.

PMID- 14696876
TI  - Reliability of a short gun questionnaire.
AB  - BACKGROUND: The purpose of the study was to develop and test a short gun
      questionnaire and compare its reliability to a long gun questionnaire to identify
      youths who may have access to or ownership of a gun. METHODS: A seven-question
      short gun questionnaire asking about gun accessibility, ownership, and usage was
      modified from the much longer gun questionnaire. To determine reliability of the
      short tool, the results of the short gun questionnaire were compared with the
      long gun questionnaire. Both the long and the short gun questionnaires were
      administered to a convenience sample of 100 consenting young people aged 10 to 24
      years old treated for any complaint. The study was approved by the institutional
      review board. RESULTS: Of the 100 youths, 66% of participants were black and 31%
      were Hispanic. The average age was 21 years and 39% were male. Two youths said
      that they had a gun, 38.0% said it would be easy to get a gun, and 25% said it
      would be impossible to obtain one. None of the youths had shared ownership of a
      gun and 4% said that there was a gun in their home, garage, or car. Eight percent
      of the youths had fired a gun in the past 6 months and 24% had fired a gun more
      than 6 months ago. The respondents' answers to all the questions in the short
      questionnaire were not statistically different from the responses in the long
      questionnaire at the P < 0.05 level. CONCLUSION: The developed short
      questionnaire provides results similar to the long questionnaire: a low number of
      gun owners but a high level of gun accessibility and availability.

PMID- 14696877
TI  - An overview of drug development in the United States and current challenges.
AB  - Drug development in the United States has undergone many changes in the past 25
      years, but relatively few fully realize the complexities involved in developing a
      new drug. Once a promising compound is identified, it must undergo preclinical
      testing, have an Investigational New Drug Application filed with the U.S. Food
      and Drug Administration (FDA), and proceed through clinical testing. When
      sufficient information is gained, a marketing application is filed with the FDA,
      who identifies it as a New Drug Application for drugs or a Biologics License
      Application for biologics. After FDA review and approval, postmarketing studies
      are frequently performed. The FDA and Congress have undertaken several
      initiatives to expand access and to accelerate drug development and review of
      investigational drugs for life-threatening and/or serious illnesses. Although the
      ultimate goal is to bring safer and more effective medical products to patients
      in a timely manner, multiple challenges face those who participate in drug
      development.

PMID- 14696878
TI  - Humor in medicine.
AB  - Humor and laughter have been a focus of attention in the popular media and in the
      medical literature. Despite statements about the health benefits of humor,
      current research is insufficient to validate such claims. There is support in the
      literature for the role of humor and laughter in other areas, including patient
      physician communication, psychological aspects of patient care, medical
      education, and as a means of reducing stress in medical professionals.

PMID- 14696879
TI  - The urban cowboy syndrome revisited: case report.
AB  - Inspired by the 1980 movie Urban Cowboy, many drinking establishments offered
      mechanical bull riding to their patrons. As the use of mechanical bulls became
      more popular, associated injuries became increasingly reported in the literature
      as the "urban cowboy syndrome." We report a case of severe straddle injury
      resulting in symphysis diastasis, urethral injury, and significant
      retroperitoneal hematoma resulting in cardiovascular instability secondary to
      mechanical bull riding. This unique case is the most severe mechanical bull
      injury reported in the literature and the only report of the urban cowboy
      syndrome since the early 1980s.

PMID- 14696880
TI  - Chinese red rice-induced myopathy.
AB  - A middle-aged man presented with joint pain and muscle weakness that had begun 2
      months before presentation. Three months before presentation, he had begun to
      take the herbal preparation Chinese red rice. Laboratory testing revealed a
      moderately elevated creatine phosphokinase level. Symptoms and laboratory
      abnormalities resolved with discontinuation of the Chinese red rice. Eight months
      later, he resumed the product and his creatine phosphokinase level rose again.
      Lovastatin is a naturally occurring component of Chinese red rice and was the
      probable cause of his myopathy.

PMID- 14696881
TI  - Ageing: the demographic volcano.

PMID- 14696882
TI  - Cutaneous leishmaniasis in Multan: species identification.
AB  - OBJECTIVE: To identify the Leishmania species being responsible for cutaneous
      leishmaniasis in Multan. METHOD: Parasites were isolated from clinically and
      parasitologically confirmed lesions of cutaneous leishmaniasis from 30 patients
      by fine needle aspiration (FNA). The bioptical materials were then cultured in
      Evans Tobie's medium and parasites isolated were identified by isoenzyme
      electrophoresis technique. RESULTS: Successful Leishmania isolates were obtained
      from 16 patients. All strains were identified by biochemical techniques as
      belonging to Leishmania tropica zimodeme MON7 variant PGD. CONCLUSION: The
      causative species was identified as Leishmania tropica.

PMID- 14696883
TI  - Effects of ciprofloxacin on foetal hepatocytes.
AB  - OBJECTIVE: To evaluate the hepatotoxic risk of Ciprofloxacin administration
      during gestation on Wistar albino rat foetuses. METHOD: An animal study carried
      on experimental pregnant female Wistar albino rats and their foetuses in the
      department of Anatomy, Basic Medical Sciences Institute, Jinnah Postgraduate
      Medical Centre, Karachi. Ciprofloxacin was administered to pregnant Wistar albino
      rats at a dose of 20 mg/kg body weight intraperitoneally (twice the therapeutic
      dose) from day-8 to day-18 of gestation. The intact rat foetuses were isolated on
      day-18 of gestation. These animals were killed by deep ether anaesthesia. Liver
      removed, weighed and fixed in 10% formalin, embedded in paraplast, 3 microm thick
      sections were cut on rotary microtome, and stained with haematoxylin and eosin.
      The histomorphological features of liver were compared with those of control
      animals and analyzed statistically. RESULTS: The study revealed that prenatal
      Ciprofloxacin produced degenerative changes in liver of foetuses. CONCLUSION: The
      results strongly suggest that Ciprofloxacin, given during pregnancy, causes
      severe liver damage in foetuses of Wistar albino rats.

PMID- 14696884
TI  - Hypoxia and pulmonary acclimatisation at 4578 m altitude: the role of
      acetazolamide and dexamethasone.
AB  - OBJECTIVES: To quantify the changes in ventilatory response and arterial blood
      gases in healthy male volunteers on acute ascent to 4578 meters altitude along
      with evaluating the role of acetazolamide and dexamethasone prophylaxis in
      acclimatisation. METHODS: Forty four lowlander male subjects participated as two
      groups in the study. Twenty four lowlander healthy male adults (age mean +/- SE
      27.8 +/- 1.24 years) comprised the non-acclimatised group. They were sub grouped
      in a double blind fashion into four. Each subgroup (n=6) received placebo
      (multivitamin) or acetazolamide (250 mg) or dexamethasone (4 mg) or combined
      regimen of the two drugs twice daily for 5 days commencing 24 hours before
      ascent. The volunteers reached the altitude of 4578 meters within a span of one
      day. The second group (acclimatised) comprised of age and height matched twenty
      volunteers who had arrived 4 and 8 weeks earlier at the same altitude. Arterial
      PO2, PCO2, SO2 and minute respiratory rate pH were measured. The pulmonary
      functions (FVC, %FEV1 PEF, FEF(25-75%) and MVV) were recorded by Compact
      Spirometer (Vitalograph). Pre and post ascent measurements were carried out in
      non-acclimatised group whereas one measurement of the same parameters were made
      in acclimatised group. RESULTS: The study revealed a significant increase in
      respiratory rate min-1 after 24 hours of ascent along with reduction in PaO2 and
      SaO2. The gradual increase in PaO2 and SaO2 and reduction in PaCO2 was observed
      after 4 weeks at the same altitude. The reduction in FVC, %FEV1, PEF, FEF(25-75%)
      and MW were recorded in our subjects after 24 hours of acute ascent.
      Nevertheless, all pulmonary parameters in volunteers having 8 weeks of stay at
      4578 m altitude, were found equivalent to the non-acclimatised group. The greater
      increase in minute respiratory rate, PaO2, SaO2 and pulmonary functions was found
      in volunteers taking acetazolamide. CONCLUSION: It is concluded that
      hyperventilation and increase in lung volumes are the adaptive pulmonary
      responses which help in improving levels of PaO2 and SaO2. The acetazolamide
      dexamethasone prophylaxis appears beneficial in promoting pulmonary
      acclimatisation during hypobaric hypoxia.

PMID- 14696885
TI  - An autopsy study of hypertrophic cardiomyopathy.
AB  - OBJECTIVE: To see the pathological features of this disease in our set up and to
      emphasise the importance of morphological examination in making the diagnosis of
      hypertrophic cardiomyopathy (HCM) especially in cases of sudden cardiac death.
      METHODS: A retrospective, descriptive study of 15 autopsies of this particular
      disease was carried out at the Armed Forces Institute of Pathology (AFI)
      Rawalpindi during the period from 1990 to 1995. The hearts along with blood
      vessels were fixed in 10% formalin and were dissected according to the modified
      Virchow's method for eliciting the gross appearance of cardiac chambers and
      valves. Representative sections were taken for histological examination. RESULTS:
      All the cases were young adult males. The age range was from 17-34 years (mean,
      26-6 years). Ten cases died suddenly and five cases had an evidence of moderate
      to severe exertion preceding their death. Symmetrical as well as asymmetrical
      hypertrophy was noted in this study. The thickness of inter ventricular septum
      (mean 20 mm) and left ventricular wall (mean 22.5 mm) was increased. All the
      specimens revealed disarray of hypertrophic myocardial fibres and patchy
      interstitial fibroses. CONCLUSION: Sudden death is usually the first
      manifestation of disease. The hearts showed asymmetric as well as concentric
      hypertrophy. Myofibre hypertrophy and disarray was an important pathological
      findings in our cases. While carrying out post-mortem examination of a case of
      sudden cardiac death one should also keep in mind the possibility of this
      disease.

PMID- 14696886
TI  - Comparison of retrobulbar anesthesia and intracameral anesthesia using
      preservative free bupivacaine hydrochloride 0.5% in phacoemulsification with
      posterior chamber intraocular lens implantation.
AB  - OBJECTIVE: To compare the retrobulbar anesthesia and intracameral anesthesia
      using preservative-free bupivacaine hydrochloride 0.5% in terms of effectiveness,
      complications and comfort to the patient during phacoemulsification with
      posterior chamber intraocular lens implantation. METHODS: This was a hospital
      based comparative study of two methods of anesthesia, conducted at LRBT Free Eye
      and Cancer Hospital, Lahore from January to July 2000. Study included 200
      patients with uncomplicated age-related cataract, equally divided in two groups
      on simple random basis. Group A (100 patients) received the retrobulbar
      anesthesia and Group B (100 patients) received the intracameral anesthesia with
      bupivacaine hydrochloride 0.5% for phacoemulsification with posterior chamber
      intraocular lens implantation. Outcome measures like pain, visual acuity,
      intraocular pressure and anterior chamber reaction were compared. RESULTS: On day
      1, 79% of the patients in group A and 82% patients in group B had unaided visual
      acuity ranging between 6/6-6/18. On day 7, this was 88% in group A and 89% group
      B. On day 1, 99% in group A and 98% in group B had <1+ cells in the anterior
      chamber while on day 7 this increased up to 100%. On day 1, 97% in group A and
      98% group B had intraocular pressure less than 20 mmHg. On day 7, it increased up
      to 100% in both groups. 97% patients in group A and 96% patients in group B had
      painless surgery. Results were analysed using computer software SPSS version
      10.0. Results showed no significant statistical difference between two groups in
      terms of pain, visual acuity, intraocular pressure, anterior chamber reaction and
      patient comfort. CONCLUSION: In the hands of expert surgeons and in selected
      patients, intracameral anesthesia with preservative-free bupivacaine
      hydrochloride 0.5% is a safe and effective technique of ocular anesthesia for
      phacoemulsification with posterior chamber intraocular lens implantation.

PMID- 14696887
TI  - Comparison of ketorolac with morphine for intra-operative analgesia in patients
      undergoing total abdominal hysterectomy.
AB  - OBJECTIVE: To compare ketorolac 0.35 mg x kg(-1) with morphine 0.1 mg x kg(-1)
      for hemodynamic stability, efficacy of analgesia and incidence of side effects in
      patients undergoing elective total abdominal hysterectomy. METHODS: Fifty ASA I
      and II patients, were enrolled in a prospective, randomized and double blind
      study. They were divided in two equal groups. Group K received Inj. Ketorolac
      0.35 mg x kg(-1) while group M received Inj. Morphine 0.1 mg x kg(-1) 5 minutes
      before induction of anaesthesia. Hemodynamic responses to laryngoscopy,
      endotracheal intubation, and surgical incision were noted. RESULTS: Data was
      entered and analysis was done using SPSS version 10.0. Student-t test and
      comparison of proportions were done where required. ANOVA was done and a p-value
      of <0.05 was considered statistically significant. There was a significant rise
      in heart rate, systolic, diastolic and mean arterial pressure in ketorolac group
      (K) as compared to baseline values at points of endotracheal intubation and
      surgical incision. Patients in Morphine group (M) showed a significant increase
      in heart rate only. There was no statistically significant difference between the
      two groups for supplemental analgesia requirement intraoperatively and
      postoperatively. Complications seen with group K were increased surgical wound
      bleeding in 2 patients (8%), nausea and vomiting in 4 patients (16%) while in
      group M there was nausea and vomiting in 5 patients (20%), and respiratory
      depression in 1 patient (4%). CONCLUSION: Although hemodynamic stability at
      points of painful stimulation was lower in patients given ketorolac as compared
      to morphine, Ketorolac has a place in the intraoperative pain relief in Pakistan
      and other developing countries where availability of powerful narcotics is
      erratic.

PMID- 14696888
TI  - Septic arthritis of the hip in children--Aga Khan University Hospital experience
      in Pakistan.
AB  - OBJECTIVE: To present clinical, radiological and bacteriological features and
      short term outcome of septic arthritis of the hip in children. METHODS: There
      were 23 male and 16 female children, including 6 neonates and 10 infants with a
      mean age of 3.9 years. Diagnosis of septic hip was made on clinical grounds,
      supplemented by X-rays, leukocyte count and the erythrocyte sedimentation rate
      (ESR). Thirty nine patients with 40 hips were followed for a mean time period of
      76 weeks. All patients had a positive joint aspirate (pus) and underwent surgical
      decompression along with intravenous antibiotic therapy. RESULTS: Symptoms of
      pain, fever and restricted range of hip motion were common to all patients. The
      mean leukocyte count was 14,000 and the mean ESR was 63 mm. Cultures of blood and
      joint aspirate were positive in 9 and 28 patients respectively. Staphylococus
      Aureus was the commonest organism (14 patients) identified, and only one patient
      had Hemophilus influenzae. Seven patients had a mixed osteoarticular infection.
      Positive clinical response was noted in the mean time period of 8.6 days. In
      follow-up, four cases developed myositis ossificans and 2 cases showed signs of
      partial growth plate destruction. CONCLUSION: Our findings of the absence of H.
      influenzae and the presence of a number of gut organisms are different from the
      previous studies. Duration of symptoms was an important prognostic factor and
      correlated well with the final outcome. Early surgical decompression was found to
      be the treatment of choice. A combined osteoarticular infection should be kept in
      mind in cases which show a poor response after the initial joint debridement.

PMID- 14696889
TI  - A differential study of breast cancer patients in Punjab, Pakistan.
AB  - OBJECTIVE: To determine the comparative pattern of distribution of four stages of
      breast cancer in 2 different hospitals in Lahore. METHODS: For all the variables
      under study test-statistic t has been used for stagewise comparisons between the
      Institute of Nuclear Medicine and Oncology (INMOL) and Shaukat Khanum Memorial
      Cancer Hospital (SKMCH) whereas the four stages of the disease were compared by
      using test-statistic F. RESULTS: The study is based on 1171 patients (672 from
      INMOL and 499 from SKMCH). This paper is an attempt to find out the pattern for
      the spread of breast cancer among its four stages and its comparative study
      between the two hospitals, at stage level. It unveils the important fact of late
      presentation of breast cancer (25% of INMOL and 36% at SKMCH) compared in 10% or
      less in international literature (18). No impact of the variables under study was
      observed (P>0.05) on the stage of the disease. CONCLUSION: Most of the cases (71%
      in INMOL and 63% (SKMCH) present at stage III and IV of breast cancer therefore
      it is necessary that attention should be made to increase the awareness about the
      need and benefits of early detection of breast cancer.

PMID- 14696890
TI  - Utility of endoscopy in infantile hypertrophic pyloric stenosis.

PMID- 14696891
TI  - Ethnopsychiatry--a review.

PMID- 14696892
TI  - Renal carcinoid tumour.

PMID- 14696893
TI  - Renal teratoma: a rare entity.

PMID- 14696894
TI  - Maffucci's syndrome--first case report from Pakistan.

PMID- 14696895
TI  - Fludarabine induced immune thrombocytopenia in a patient with CD5 positive B cell
      chronic lymphocytic leukemia.

PMID- 14696896
TI  - Widespread skeletal tuberculosis in a two years old girl.

PMID- 14696897
TI  - Depressive disorder: diagnosis and management in general practice in Pakistan.
AB  - OBJECTIVE: To formulate guidelines for diagnosis and management of depressive
      illness in general practice in Pakistan. METHODS: Using guidelines developed
      through research in primary care, this article explains how depressive illness
      could be diagnosed using diagnostic and statistical manual (DSM) criteria and
      managed systematically at general practice level in Pakistan. RESULTS: Diagnosing
      depression accurately and choosing the right anti-depressant and giving it for
      adequate length of time are crucial factors in effective management of
      depression. CONCLUSION: Depressive illness can be diagnosed and managed
      effectively in general practice in Pakistan and only a minority of patients would
      need to be referred to psychiatrists.

PMID- 14696898
TI  - Bidirectional cavopulmonary shunt for cyanotic heart disease: surgical experience
      from a developing country.
AB  - OBJECTIVE: The importance of bidirectional cavopulmonary anastomosis for
      palliation of complex cyanotic congenital heart disease is widely recognized.
      This study was conducted to highlight our surgical experience with this procedure
      in a developing country. METHODS: A retrospective study was conducted using
      medical records at the Aga Khan University Hospital, Karachi, Pakistan. Clinical
      findings at presentation, anatomical defects seen on transthoracic
      echocardiography, pre-operative McGoon index, cardiopulmonary bypass time, use of
      cardioplegia, post-procedure oxygen saturations and complications were evaluated.
      RESULTS: A total of 8 patients underwent bidirectional cavopulmonary anastomosis.
      There were 6 males (75%) and 2 females (25%). Ages and weights at operation
      averaged 5.7 +/- 3.7 years (range 2-14 years) and 18.6 +/- 10.4 kg (range 8.5
      35.5 kg) respectively. The most common symptoms were the presence of cyanosis in
      all (100%) patients followed by recurrent respiratory tract infections in 3
      (37.5%) patients. Transthoracic echocardiography revealed 6 (75%) patients with
      atrial septal defects, 5 (62.5%) with tricuspid atresia, 3 (37.5%) with
      ventricular septal defects, 3 (37.5%) with malposition of great vessels, 2 (25%)
      with pulmonary stenosis and 2 (25%) with double inlet left ventricles. The mean
      pre-procedure McGoon index was 2.1 +/- 0.5 (range 1.37-2.80). All patients
      received cardioplegia. Cardiopulmonary bypass was used in all patients for a mean
      time of 154.1 +/- 83.6 minutes (range 60-298 minutes). All patients were
      ventilated for a mean period of 1.5 +/- 0.7 days (range 1-3 days). The ICU stay
      was 3.0 +/- 0.6 days (range 2-5 days) with a total hospital stay of 9.8 +/- 3.8
      days (range 7-18 days). The mean post-procedure oxygen saturation was 82.6 +/-
      3.5% (range 76-86%). The most common post-operative complication was
      supraventricular arrhythmia in 2 (25.0%) patients. There were no intra-operative
      or early (within 7 days of procedure) deaths. One patient developed pulmonary
      artery hypertension and died 23 months later due to cardiac arrest. CONCLUSION:
      Patients tolerated the procedure well. After a mean follow-up of 10 months, 6
      patients were assessed to be in New York Heart Association (NYHA) functional
      class I and one patient in NYHA class II. Clinical and post-procedural data
      gathered from our experience confirms the safety of bidirectional cavopulmonary
      anastomosis.

PMID- 14696899
TI  - Functional magnetic resonance imaging of phonologic processing in
      neurofibromatosis 1.
AB  - Neurofibromatosis 1 is associated with reading disabilities, but few associations
      between neuroanatomic abnormalities and reading problems have been found. We
      examined the neuronal bases for phonologic processing, a core component of
      learning to read, in 15 individuals with neurofibromatosis 1 and 15 controls
      using functional magnetic resonance imaging (MRI). Our results revealed
      differential use of inferior and dorsolateral prefrontal cortical areas relative
      to posterior (temporal, parietal, and occipital) cortices for participants with
      neurofibromatosis 1 compared with controls during phonologic (rhyme) decisions.
      In addition, similar to previous brain imaging studies of reading deficits in the
      general population, poorer performance on one of the phonologic decision tasks
      was associated with increased signal change in the right superior temporal gyrus
      for the neurofibromatosis 1 group. Behavioral performance on the functional MRI
      tasks was related to academic reading measures for the neurofibromatosis 1 group.
      The differential patterns of functional connectivity observed here lend support
      to previous morphologic studies that suggested inferior frontal and superior
      temporal areas to be important mediators of reading and language development in
      neurofibromatosis 1.

PMID- 14696900
TI  - Epidemiology of childhood Guillain-Barre syndrome as a cause of acute flaccid
      paralysis in Honduras: 1989-1999.
AB  - The objective of this study was to investigate the incidence of acute flaccid
      paralysis in the pediatric population of Honduras over an 11-year period,
      determine what percentage of acute flaccid paralysis was Guillain-Barre syndrome,
      and identify the epidemiologic features of Guillain-Barre syndrome. There were
      546 childhood cases of acute flaccid paralysis seen between January 1989 and
      December 1999 at the Hospital Escuela Materno-Infantil in Tegucigalpa, Honduras.
      Of these cases with acute flaccid paralysis, 394 (72.2%) were diagnosed with
      Guillain-Barre syndrome. Our incidence of Guillain-Barre syndrome in the Honduran
      pediatric population (1.37/100,000 per year) is higher than that shown in other
      studies. There was a significantly higher incidence of Guillain-Barre syndrome in
      younger children (ages 1-4 years), a significant preponderance of cases from
      rural areas, and a mild predominance in boys but a typical clinical presentation.
      The Honduran pediatric Guillain-Barre syndrome population had an increased
      mortality rate. Guillain-Barre syndrome has become the leading cause of childhood
      paralysis in Honduras. A better understanding of the population at highest risk
      and opportunities for earlier intervention with more effective therapeutic
      modalities may permit reducing the mortality among Honduran children who develop
      Guillain-Barre syndrome.

PMID- 14696901
TI  - Regulatory disorders in Israeli infants: epidemiologic perspective.
AB  - The concept of regulatory disorders has been clinically defined. However,
      epidemiologic validity has not yet been investigated. Children between the ages
      of 6 and 36 months (N = 450) were included in the study. Two age groups were
      analyzed separately: 6 to 17 months (53%) and 18 to 36 months (47%). A specially
      designed questionnaire in Arabic and Hebrew pertaining to the physiologic and
      behavioral aspects of regulatory disorders was administered at the mother and
      child health clinics in northern Israel. It was established in the present study
      that a minimum of four regulatory items should be reported for the diagnosis of a
      regulatory disorder, as perceived by parents. Factor analysis revealed 6 and 10
      different aggregates of regulatory items in the young and older age groups,
      respectively. The general prevalence of regulatory disorder as defined in the
      present study was found to be 18%. Age, maternal education, and sex were found to
      be significantly related to the prevalence of regulatory disorders. No difference
      in the prevalence of regulatory disorders between Arab and Jewish infants was
      found. Further validations of the concept of regulatory disorder as well as
      devising appropriate measurements in well-designed studies are warranted.

PMID- 14696902
TI  - Vermian hypoplasia and arrested cerebral myelination in two sisters: variant of
      Joubert's syndrome or a new syndrome?
AB  - Two adult sisters have vermian hypoplasia, ataxia, nystagmus, pontine divergence
      insufficiency, and mild to moderate intellectual disability, with an arrest of
      cerebral myelination resembling the pattern of a 4-month-old infant. Other
      abnormalities include high myopia, optic nerve hypoplasia, decreased bone
      density, hypoplasia of the secondary teeth, and amenorrhea. We did not find
      matching patients described in the literature. The sisters could represent a
      variant of one of the described syndromes of the cerebellocerebro-oculorenal
      spectrum, such as a variant of Joubert's syndrome, or a disorder sui generis
      within the spectrum.

PMID- 14696903
TI  - Sleep organization in children with partial refractory epilepsy.
AB  - Although it is currently known that sleep can influence epilepsy and epilepsy can
      influence sleep organization, few data have been published on this mutual
      interaction concerning the pediatric population. The objective of this study was
      to verify the eventual presence of sleep alterations in children with partial
      refractory epilepsy. Seventeen patients with partial refractory epilepsy were
      submitted to whole-night polysomnography as part of their epilepsy investigation.
      Polysomnographic recordings were performed on a digital video
      electroencephalography (EEG) system and consisted of the registration of EEG (24
      channels), electro-oculogram, electromyogram, electrocardiogram, and nasal
      airflow and abdominal respiratory movements. Sleep stages were visually scored
      following standard criteria, and ictal events were classified according to the
      international classification of seizures. The patients were also subdivided into
      two subgroups based on the presence or absence of ictal episodes during the
      recording night. The results concerning sleep organization were compared with
      those obtained from a normal control group. The analysis of the sleep parameters
      showed a reduction of total time in bed and total sleep time in both subgroups of
      epileptic children; there was a higher number of stage shifts per hour in the
      control group than in both epileptic subgroups. The percentage of stage 2 shifts
      is significantly reduced in patients with epilepsy and seizures during the night
      and the percentage of stage 3 to 4 shifts is increased. Nonsignificant
      differences are evident for the number of awakenings per hour and the percentage
      of stage 1 shifts. The percentage of rapid eye movement (REM) sleep is reduced,
      and first REM latency is increased in both epileptic subgroups, compared with
      normal controls, without statistical significance. Nine of 17 patients had
      seizures during the polysomnographic recording; nocturnal ictal events occurred
      mostly during non-REM sleep stage 2. Our results show that patients with partial
      refractory epilepsies have only mild sleep structure abnormalities, and this can
      be considered as an effect of the epileptic syndrome per se or as a result of the
      chronic antiepilepsy drug treatment.

PMID- 14696904
TI  - Ten-year prospective study (clinical spectrum) of childhood Guillain-Barre
      syndrome in the Arabian peninsula: comparison of outcome in patients in the pre-
      and post-intravenous immunoglobulin eras.
AB  - A prospective study of Guillain-Barre syndrome from January 1992 to December 2001
      was undertaken. Intravenous immunoglobulins were used in all patients. All
      patients were followed up until complete recovery. Various parameters, such as
      onset of weakness, duration of hospital stay, ventilation requirement, residual
      deficit, and mortality, were recorded. Acute relapses and fluctuations were also
      noted. The pattern of this group was compared with patients before 1992, who were
      not given intravenous immunoglobulins in the Sultanate of Oman. Our data were
      compared with a few studies prior to 1992 from the medical literature. Our study
      revealed a definite benefit with intravenous immunoglobulins. The disease course
      and hospital stay were shortened. Fewer patients needed ventilation. There was no
      mortality, and the residual deficit was less than 5%. Occasional relapses at a
      later stage in the course of illness have been noted in acute Guillain-Barre
      syndrome. However, acute relapse, a new phenomenon that was not seen in the pre
      intravenous immunoglobulin era, stood at 11.9%. Intravenous immunoglobulins have
      made a significant difference in the outcome of Guillain-Barre syndrome, but one
      has to be aware of acute relapses, which usually occur in the first 2 to 3 weeks
      after administration.

PMID- 14696905
TI  - Parental satisfaction with sumatriptan nasal spray in childhood migraine.
AB  - Migraine headaches are a frequently encountered neurologic problem in children.
      The utility of the triptans has not been as clearly documented in this
      population, although it is well delineated in acute migraine attacks in adults.
      We conducted a retrospective chart review of our experience with using
      sumatriptan nasal spray in children aged 5 to 12 years from our headache clinic
      population with migraine headaches. The nasal spray formulation is used
      frequently in our clinic population with patients who have failed over-the
      counter therapy with ibuprofen or acetaminophen. None of the triptans are
      approved by the US Food and Drug Administration for use in children or
      adolescents (12 years and older). One hundred of these patients were identified,
      and their parents or guardians completed a standardized questionnaire regarding
      their child's response to sumatriptan nasal spray in acute migraine. Fifty-seven
      of 100 families completed the questionnaire, and 44 of 57 families (77%) reported
      good to excellent relief of their child's migraine attacks with sumatriptan nasal
      spray. In our cohort of pediatric patients, sumatriptan nasal spray was effective
      and well tolerated when used for abortive therapy of acute migraine attacks.

PMID- 14696906
TI  - Hemimegalencephaly: part 2. Neuropathology suggests a disorder of cellular
      lineage.
AB  - Cerebral tissue from hemispherectomy in three children (two 4-month-old girls and
      one 4-year-old boy) with hemimegalencephaly was studied using histochemical and
      immunocytochemical markers of neuronal and glial maturation and identity.
      Histologic abnormalities of cellular growth and cytomorphology, including
      "balloon cells," were present in both gray and white matter, in addition to
      disorganized tissue architecture. Cells in the mitotic cycle were absent. Many
      hypertrophic, atypical cells with enlarged processes exhibited mixed or ambiguous
      lineage, with immunoreactivity for both glial (glial fibrillary acidic protein
      [GFAP]; S-100beta) and neuronal proteins (microtubule-associated protein 2
      [MAP2], neuronal nuclear antigen, chromogranin A, and neurofilament protein
      [NFP]). Strong vimentin reactivity was present in neurons, as well as glial cells
      and cells of mixed lineage, suggesting incomplete maturation. Synaptophysin
      reactive axons terminated on a minority of balloon cells and on most heterotopic
      single neurons in white matter, confirmed by electron microscopy, demonstrating
      that single heterotopic neurons are not synaptically "isolated," as they may
      appear; thus, they are capable of contributing to epilepsy. Oligodendrocytes are
      the least affected cells, at least in some cases. The findings are reminiscent of
      the hamartomas of tuberous sclerosis. We conclude that hemimegalencephaly is a
      primary disorder of neuroepithelial lineage and cellular growth. A migratory
      disturbance contributes to disorderly tissue architecture but is secondary. No
      pathologic difference is detected between isolated and syndromic forms of
      hemimegalencephaly.

PMID- 14696907
TI  - The International Child Neurology Association: personal view.

PMID- 14696908
TI  - Impact of the Journal of Child Neurology: 2002 data.
AB  - The Journal of Child Neurology (JCN) began in 1986 as a quarterly publication
      focused on child neurology and the related clinical pediatric neuroscience areas
      of pediatric neurosurgery, child psychiatry, pediatric neuroradiology, and
      developmental and behavioral pediatrics. As submitted material increased, JCN
      expanded in publication frequency and now appears monthly. Article quality has
      always been high and many articles have been frequently cited. Over the years,
      the ratings produced for the ISI Journal Citation Reports have identified JCN as
      a high-ranking pediatric journal based upon the impact factor value. Currently
      (year 2002 figures), JCN (with its impact factor of 1.338) ranks 24th out of 68
      pediatric journals.

PMID- 14696909
TI  - Silent stroke in a case of beta-thalassemia major associated with chronic renal
      failure and diabetes mellitus.
AB  - Severe anemia, growth retardation, diabetes mellitus, cardiac disorders, and,
      infrequently, stroke are well-known complications of thalassemia major. We report
      a girl, age 7 years, 2 months, with beta-thalassemia major associated with
      chronic renal failure, diabetes mellitus, and cardiomyopathy in whom a silent
      stroke was noted during follow-up. She was diagnosed with thalassemia major at
      age 6 months, chronic renal failure at age 3 years, 3 months, and diabetes
      mellitus and cardiomyopathy at age 7 years. Although cranial computed tomography
      was found to be normal at the age of 3 years, 3 months, magnetic resonance
      imaging showed cerebral infarct in the right frontal region at 7 years, 2 months.
      A thrombophilic panel revealed increased factor VIII and decreased protein C
      concentrations. She died from disseminated intravascular coagulation at age 7
      years, 9 months. We did not record any clinical findings of stroke during her
      follow-up. We think that diabetes mellitus, dilated cardiomyopathy, and increased
      factor VIII and decreased protein C concentrations led to the occurrence of
      cerebral infarct. In conclusion, we emphasize that children with thalassemia
      major should be monitored closely for stroke. We also suggest that stroke can
      show a silent progression in severely affected children, as in our case.

PMID- 14696910
TI  - A child with Diamond-Blackfan anemia, methylenetetrahydrofolate reductase
      mutation, and perinatal stroke.
AB  - Diamond-Blackfan anemia is a congenital hypoproliferative anemia known to be
      associated with diverse physical anomalies affecting the thumb, craniofacial
      bones, urogenital system, and heart; prematurity; and fetal demise. We report the
      case of a 16-month-old boy with Diamond-Blackfan anemia noted to have decreased
      use of his right side since birth. Magnetic resonance imaging demonstrated a
      large area of encephalomalacia in the left middle cerebral artery territory.
      Magnetic resonance angiography showed marked attenuation of the left middle
      cerebral artery, suggesting a remote thromboembolic event. The laboratory results
      were remarkable for a decreased hemogolobin of 9.5 g/dL and increased platelets
      of 591,000/microL. He was heterozygous for the methylenetetrahydrofolate
      reductase gene C677T mutation. An echocardiogram demonstrated a patent foramen
      ovale versus an atrial septal defect with left to right shunting. Perinatal
      stroke may be a rare complication of Diamond-Blackfan anemia in the setting of
      other risk factors.

PMID- 14696911
TI  - Periodic lateralized epileptiform discharges in children.
AB  - Thirteen children in whom electroencephalography revealed periodic lateralized
      epileptiform discharges in the acute phase of cerebral involvement were included
      in this study. Four were diagnosed as having influenza-associated encephalopathy,
      two nonherpetic limbic encephalitis, two theophylline-associated seizures, one
      Mycoplasma pneumoniae encephalitis, one acute encephalopathy, and one bacterial
      meningitis. All patients developed seizures; six developed hemiconvulsions. As to
      prognosis, two died, six had some neurologic sequelae, and five had no neurologic
      sequelae. Although periodic lateralized epileptiform discharges are not disease
      specific, the importance of these disorders had not been focused on as a cause of
      periodic lateralized epileptiform discharges.

PMID- 14696912
TI  - Hydrogen peroxide neurotoxicity in childhood: case report with unique magnetic
      resonance imaging features.
AB  - Concentrated hydrogen peroxide (H2O2) intoxication is relatively rare in
      children. Serious irreversible neurotoxicity generally results. The case of an 11
      year-old boy who inadvertently drank a concentrated (35%) H2O2 solution is
      described. He exhibited signs of an acute encephalopathy with cortical visual
      impairment. Extensive cerebrocortical diffusion restriction with apparent gyral
      edema was evident at 3 days following ingestion, particularly in the parieto
      occipital regions bilaterally. Spontaneous neurologic improvement quickly
      followed, and nearly full clinical resolution was evident 1 month later. The
      pattern of imaging abnormalities closely resembles that of reversible posterior
      leukoencephalopathy. Concentrated H2O2 neurotoxicity in children can exhibit
      unique patterns (a reversible posterior leukoencephalopathy) and a better than
      expected outcome.

PMID- 14696913
TI  - Mild elevation of N-acetylaspartic acid and macrocephaly: diagnostic problem.
AB  - Patients with slightly increased excretion of N-acetylaspartic acid in urine,
      together with macrocephaly, present a dignostic dilemma for Canavan's disease. We
      describe a 13-year-old male patient with macrocephaly, mild developmental delay,
      increased signal intensity in the basal ganglia bilaterally, partial cortical
      blindness, and retinitis pigmentosa. Although the clinical course and magnetic
      resonance imaging findings did not resemble typical Canavan's disease, N
      acetylaspartic acid excretion in the patient's urine was slightly elevated, 99.90
      +/- 4.00 microg/mg creatinine, whereas the normal control range was < 83
      microg/mg creatinine. Cultured skin fibroblasts from the patient showed no
      aspartoacylase activity. Cloning of genomic DNA isolated from the patient's
      fibroblasts showed an intronic mutation, specifically deletion of -2A and -3C at
      the acceptor site of exon 3 and disrupting the normal splicing of the gene. A
      second mutation was found in exon 6, 863 A-->G in aspartoacylase complementary
      DNA, causing a tyrosine-to-cysteine (Y288C) amino acid substitution. Expression
      of the mutation on exon 6 showed normal aspartoacylase activity. These data
      suggest that expression of the mutation may help to understand the enzyme defect
      in a patient with slightly increased N-acetylaspartic acid excretion.

PMID- 14696914
TI  - Toxic pediatric parkinsonism: report of a child with metabolic studies and
      response to treatment.
AB  - We successfully treated a child with parkinsonism secondary to cytosine
      arabinoside with levodopa/carbidopa and attempted to elucidate the pathogenesis
      of the disorder by sequential analysis of cerebrospinal fluid biogenic amines,
      sequential magnetic resonance imaging, and fluorodopa positron emission
      tomography, which revealed both permanent and reversible biochemical and
      structural alterations. The parkinsonian disorder resolved in 9 months. Metabolic
      changes and structural abnormalities on imaging studies were chronologically
      correlated with the clinical course.

PMID- 14696915
TI  - Microanalysis of nucleic acids using the limulus G test.
AB  - The limulus G test has been used as a quantitative analysis of (1-->3)-beta-D
      glucans, including schizophyllan (SPG) and curdlan. The present work extended the
      limulus G test to detect polynucleotide/SPG complexes. The complex showed an
      extremely sensitive response to the test, compared with SPG itself. The minimum
      concentration of the complex to show the response is almost 10-times as small as
      that of SPG itself, indicating the possibility to detect (1-->3)-beta-D-glucans
      or/and polynucleotides on the pico gram/ml scale.

PMID- 14696916
TI  - Protein-immobilized electrode for rapid and convenient sensing of thyroid hormone
      receptor-ligand interaction.
AB  - The recombinant human thyroid hormone receptor (TR) was expressed as an in-frame
      fusion with ten consecutive histidine residues using a bacterial system; then the
      receptor was immobilized on an Au-electrode with Ni(II)-mediated chemisorption
      using the histidine tag and thiol-modified nitrilotriacetic acid. The receptor
      modified electrode could rapidly detect ligand binding to hTR without any
      separation procedures, and showed a good response in a concentration-dependent
      manner. The sensitivity of this biosensor based on ligand-receptor interactions
      was comparable to those of conventional competitive ligand binding assays using
      radio-labeled ligands. Our results strongly suggest that our new biosensor can be
      applied to the identification of new ligands for hTR.

PMID- 14696917
TI  - Presence of exclusively bacteriochlorophyll-c containing substrain in the culture
      of green sulfur photosynthetic bacterium Chlorobium vibrioforme strain NCIB 8327
      producing bacteriochlorophyll-d.
AB  - The light-dependent composition change of light harvesting
      bacteriochlorophyll(BChl)s in the present culture of a green sulfur
      photosynthetic bacterium Chlorobium (Chl.) vibrioforme f. sp. thiosulfatophilum
      strain NCIB 8327 was investigated by visible absorption spectroscopy and HPLC
      analyses. When the culture was repeatedly grown in liquid media under a low light
      condition, both the Soret and Qy absorption bands of the in vivo spectrum were
      shifted to longer wavelengths. Analysis of the extracted pigments by HPLC
      revealed that the ratio of the amount of BChl-c to that of BChl-d molecules
      gradually increased during repeated cultivation. In contrast, when the culture
      grown under a low light intensity was transferred to a high light condition and
      continued to be grown, the absorption bands were shifted to shorter wavelengths
      and the ratio of BChls-c/d decreased finally to the almost original value.
      Colonies were prepared on solid agar media from the liquid culture containing
      both BChls-c and d, which was grown under a low light intensity. Each colony
      obtained was found to contain either BChl-c or d, but not both of them. Two types
      of cells isolated in this study were derived from the same clone, judged from
      their genetic analyses. The variation of pigment composition in our liquid
      culture observed here could be ascribed to the difference of growth rates between
      two substrains containing BChl-c and BChl-d, respectively, depending on light
      conditions.

PMID- 14696918
TI  - Continuous measurement of glutamate and hydrogen peroxide using a microfabricated
      biosensor for studying the neurotoxicity of tributyltin.
AB  - We first measured the effects of trace levels of an endocrine disruptor,
      tributyltin (TBT), on the secretion response from nerve cells using a
      microfabricated biosensor designed for the continuous measurement of L-glutamate
      and hydrogen peroxide. We observed higher and long-lasting glutamate and hydrogen
      peroxide concentrations from the cells when cultured rat cortical neurons were
      exposed to TBT. Glutamate and hydrogen peroxide release was induced even when we
      reduced the TBT concentration to 10 nM. This concentration is about two orders of
      magnitude lower than the concentration that induced apoptosis-like cell death. We
      also report on the effects of NMDA and non-NMDA receptor antagonists, which can
      help us to understand the mechanism of TBT neurotoxicity.

PMID- 14696919
TI  - Determination of trace procaine hydrochloride by differential pulse adsorptive
      stripping voltammetry with a Nafion modified glassy carbon electrode.
AB  - A sensitive and selective method for the determination of procaine hydrochloride
      with a Nafion-modified glassy carbon electrode has been developed. The
      voltammetric behavior of procaine hydrochloride on the Nafion-modified electrode
      indicated that the modified electrode not only increased the sensitivity of the
      determination of procaine hydrochloride, but also catalyzed the electrode
      process. Procaine hydrochloride was accumulated in Britton-Robinson buffer (pH
      2.09) at a potential of -0.2 V (vs. SCE) for 180 s, and was then determined by
      differential pulse adsorptive stripping voltammetry. The effect of various
      parameters, such as the pH of the medium, the mass of drop-coated Nafion, the
      accumulation potential, the accumulation time and the scan rate, were
      investigated. Under the optimum conditions, a linear calibration graph was
      obtained in the concentration range of 6.0 x 10(-8) to 6.0 x 10(-6) mol l(-1)
      with a correlation coefficient of 0.9987. The relative standard deviation was
      4.18% for eight successive determinations of 1.0 x 10(-7) mol l(-1) procaine
      hydrochloride, and the detection limit (three times signal to noise) was 7.0 x
      10(-9) mol l(-1). A study of interfering substances was also performed, and the
      method was applied to the direct determinations of procaine hydrochloride in the
      injection solution of procaine hydrochloride and in rabbit serum.

PMID- 14696920
TI  - Analyses of anandamide and endocannabinoid-like compounds using collision-induced
      dissociation in fast atom bombardment ionization-mass spectrometry and gas
      chromatography/chemical ionization-mass spectrometry.
AB  - The utility of the collision-induced dissociation (CID) of two different forms of
      precursor cations generated by the fast atom bombardment (FAB) ionization of N
      arachidonylethanolamine (anandamide) and a series of endocannabinoid-like
      compounds, such as N-oleoylethanolamine, N-palmitoylethanolamine, N
      stearoylethanolamine, N-linoleoylethanolamine, N-oleoylpropanolamine, and N
      palmitoylpropanolamine, as a method of providing general information on their
      characterizations was examined. The CID spectra of lithium-adduct [M+Li]+ ions of
      the amines with unsaturated hydrocarbon chains were rich in structurally
      informative charge-site-remote (CSR) fragmentation patterns that provide
      information on the locations of double bonds in hydrocarbon chains. On the other
      hand, the CID reactions of [M+H]+ ions produced acylium ions that are derived
      from the cleavage of amide bonds, thus providing information on the size of the
      hydrocarbon chains, although CSR fragmentations were not observed. These
      compounds without derivatization were analyzed using gas chromatography/chemical
      ionization-mass spectrometry (GC/CI-MS) with a polyethylene glycol phased column
      with fused silica capillary pre-tubing. Identifiable molecular-related [M+H]+
      ions were observed.

PMID- 14696921
TI  - Structure identification of five unknown dilipo-alkaloids extracted from
      processed tuber of Aconitum Carmiechaeli by electrospray ionization tandem mass
      spectrometry.
AB  - The alkaloids in processed aconite tuber of Aconitum Carmiechaeli were studied,
      and five novel alkaloids in extract from processed aconite tuber were found. The
      first step involved the use of electrospray ionization mass spectrometry (ESI
      MS), and then multi-stage tandem mass spectrometry (MSn) was used to provide
      structural information. Based on their MSn spectra, the structures of the five
      novel compounds were elucidated to be C3,C8-difatty acid esters of mesaconitine,
      aconitine and 10-hydroxyaconitine.

PMID- 14696922
TI  - Development of a simultaneous analysis method for carbofuran and its three
      derivative pesticides in water by GC/MS with temperature programmable inlet on
      column injection.
AB  - A simultaneous analytical method was examined for carbofuran and its derivative
      pesticides in water. Since carbofuran derivatives are hydrolyzed to carbofuran in
      water, the liquid-liquid extraction method was used to obtain an accurate
      concentration value. Moreover, since these compounds are easily decomposed at the
      GC/MS injection port, temperature programmable inlet on-column injection was
      used. By combining the two methods, a sensitive analytical method was established
      without hydrolysis and thermal decomposition. As a result of recovery experiments
      using distilled water, river water and tap water, acceptable recovery rates and
      favorable reproducibility were obtained. This method was used in a field
      investigation to determine carbofuran and its derivative pesticides in river
      water taken from three points of the Y river over a period of one year.
      Carbofuran, benfuracarb, and carbosulfan were detected and corresponded to the
      period when these pesticides were used in the area. Although benfuracarb and
      carbosulfan using traditional methods are believed to easily hydrolyze and
      thermally decompose during the analytical process, by using our method they can
      be detected.

PMID- 14696923
TI  - Identification of a metallothionein in Synechococcus by capillary electrophoresis
      hyphenated with inductively coupled plasma mass spectrometry.
AB  - A home-made system hyphenating capillary electrophoresis with an inductively
      coupled plasma mass spectrometer (CE-ICP-MS) for cadmium speciation of protein
      binding and free cadmium ions in solution is presented. The CE-ICP-MS interface
      consisted of an acrylic block with an internal volume ca. 20 microL in which a
      platinum electrode, a capillary column, and a connection to an ICP nebulizer were
      inserted. A make-up electrolyte solution containing 50 mmol L(-1) Tris-HCl buffer
      solution (pH 9.0) was continuously flowed through the interface to the ICP
      nebulizer. The separation of free Cd ions, Cd-cysteine, and Cd bounded to
      metallothionein (MT) isoforms from rabbit liver was carried out by capillary
      electrophoresis, and the analytes were detected by ICP-MS. The feasibility to
      isolate metallothionein compounds extracted from the cyanobacterium Synechococcus
      PCC7942 was demonstrated. The Cd binding proteins were induced in Synechococcus
      PCC7942 and further analyzed by CE ICP-MS.

PMID- 14696924
TI  - Estimation of organophosphoric acid triesters in soft polyurethane foam using a
      concentrated sulfuric acid dissolution technique and gas chromatography with
      flame photometric detection.
AB  - A concentrated sulfuric acid dissolution technique and a GC method are described
      for the estimation of tributyl phosphate, tris(2-chloroethyl) phosphate,
      tris(chloropropyl) phosphate, tris(1,3-dichloro-2-propyl) phosphate, triphenyl
      phosphate and tris(butoxyethyl) phosphate in soft polyurethane foam. A soft
      polyurethane foam sample containing organophosphoric acid triesters was dissolved
      in concentrated sulfuric acid. The solution was added to water, where only the
      polyurethane was separated out. The pH of the solution was adjusted, and
      organophosphoric acid triesters were extracted with toluene. After purification,
      the compounds were determined by GC. The detection limits of the organophosphoric
      acid triesters were 0.3 - 0.9 microg g(-1). The recoveries of the
      organophosphoric acid triesters from a 0.05 g sample of soft polyurethane foam
      were 80.0 - 90.0%, when the spiked amounts were 0.25 - 1 microg. The compounds
      were detected from soft polyurethane foam at the level of 0.4 - 23.3 microg g(
      1).

PMID- 14696925
TI  - Separation of gold, palladium and platinum from metallurgical samples using an
      amberlite XAD-7 resin column prior to their atomic absorption spectrometric
      determinations.
AB  - A simple and sensitive method for the separation and preconcentration of gold,
      palladium and platinum has been established prior to their atomic absorption
      spectrometric determinations. Analytes from 0.5 mol dm(-3) KI in a 2 mol dm(-3)
      HCl solution were recovered using an Amberlite XAD-7 column as halogeno
      complexes. The effects of some analytical parameters, including reagent amounts,
      sample volume and flow rates, on the quantitative recoveries of gold, palladium
      and platinum were investigated. The influences of some diverse ions were also
      studied. The proposed method has been applied for the preconcentration and
      separation of analytes from pure copper and anodic slime samples with
      satisfactory results (recoveries > 95%, relative standard deviations < 9.0%,
      relative error < or = 5%).

PMID- 14696926
TI  - Determination of rare earth elements in geological samples by inductively coupled
      plasma atomic emission spectrometry with flow injection liquid-liquid extraction.
AB  - A direct sampling with organic solvent extracts for simultaneous multi-element
      determination implemented with inductively coupled plasma atomic emission
      spectrometry (ICP-AES) associated with a flow injection liquid-liquid extraction
      (FI-LLE) sample preconcentration method was studied. The "robustness" of the
      plasma discharge with tributyl phosphate (TBP) loading was diagnosed by using the
      Mg II 279.55 nm and Mg I 285.21 nm lines intensity ratio. A FI-LLE
      preconcentration system for rare earth elements (REEs)-nitrate-TBP was
      established by using a laboratory-designed phase separator. For these elements,
      an average sensitivity enhancement factor of 64 was obtained with respect to ICP
      AES sampling with aqueous solutions. The precision of the method was
      characterized by a relative standard deviation (%RSD) of 1.8 - 5.2%. A throughput
      of 27 samples per hour can be achieved with an organic solvent consumption of
      less than 200 microl per determination. Good results were obtained for the
      analysis of standard reference materials.

PMID- 14696927
TI  - Nickel as a chemical modifier for sensitivity enhancement and fast atomization
      processes in electrothermal atomic absorption spectrometric determination of
      cadmium in biological and environmental samples.
AB  - A systematic study of the efficiency of protons, Ni, Pd and Th as chemical
      modifiers for the determination of cadmium by electrothermal atomic absorption
      spectrometry (ETAAS) using fast temperature programs was made for platform
      atomization. A comparison was made in terms of the salt type, absorbance-time
      profiles and elimination of the sodium chloride interference. The results were
      adapted to develop a method for the ETAAS determination of cadmium in biological
      and environmental samples. The highest sensitivity to determine cadmium in
      biological and environmental samples was obtained using nickel (together with
      protons) as a chemical modifier. The accuracy of the method was tested by the
      determination of cadmium in different certified reference materials. The best
      detection limit and the characteristic mass of Cd were found to be 0.03 ng mL(-1)
      and 0.35 pg, respectively.

PMID- 14696928
TI  - Effects of the molecular properties of mixed solvents on the elution of alkyl
      benzoates in RPLC.
AB  - The retention behavior and mechanism of methyl, ethyl, propyl, isopropyl, buthyl
      and isobuthyl benzoates have been studied at different eluent compositions of
      aqueous mixtures with water-soluble organic solvents (methanol, ethanol, 1
      propanol, 2-propanol, acetonitrile (AN), 1,4-dioxane and tetrahydrofuran (THF))
      in RPLC. The retention of the solutes is discussed based on the solvent
      composition, solvent polarity (ETN value), preferential solvation, hydrogen
      bonding and solvent clusters of the eluents. The smaller ETN values and the
      larger preferential solvation of the mixed solvent eluted the solutes faster. The
      IR spectra of HDO suggested that the solvents, except for methanol and ethanol,
      break the hydrogen bonding between water molecules, resulting in fast elution of
      the solutes. Based upon the results, we chose an optimum solvent composition for
      the separation of benzoates and applied it to the determination of the benzoates
      in clove.

PMID- 14696929
TI  - Flow-injection chemiluminescence determination of formaldehyde with a bromate
      rhodamine 6G system.
AB  - In this paper, a novel flow-injection chemiluminescence (CL) system for the
      determination of formaldehyde is described. It is based on a strong enhance
      effect of formaldehyde on the weak CL emission of the reaction between potassium
      bromate and rhodamine 6G in a sulfuric acid medium. A possible mechanism for this
      CL reaction is proposed. A CL calibration graph was linear in the range of 0.8 -
      200 microg l(-1) and the detection limit was 0.3 microg l(-1) (3sigma). The
      relative standard deviation was less than 3% for 10 microg l(-1) formaldehyde (n
      = 11). The method has been applied to determine formaldehyde in the air samples.

PMID- 14696930
TI  - Simultaneous determination of choline and acetylcholine based on a trienzyme
      chemiluminometric biosensor in a single line flow injection system.
AB  - A detector for the simultaneous determination of choline (Ch) and acetylcholine
      (ACh) based on a sensitive trienzyme chemiluminometric biosensor in a single line
      flow injection (FI) system is described. Immobilized choline oxidase (ChOx),
      immobilized peroxidase (POx), immobilized acetylcholinesterase, and coimmobilized
      ChOx/POx were packed, in turn, in a transparent ETFE tube (1 mm i.d., 75 cm) and
      the tube was placed in front of a photomultipier tube as a flow cell. Two-peak
      response was obtained by one injection of the sample solution. The first and
      second peaks were dependent on the concentrations of Ch and ACh, respectively.
      The influence of some experimental parameters such as flow rate, amounts of
      immobilized enzymes on the behavior of the sensor was studied in order to
      optimize the sensitivity, sample throughput and resolution. Calibration curves
      were linear at 1 - 1000 nM for Ch and 3 - 3000 nM for ACh. The sample throughput
      was 25/h without carryover. The FI system was applied to the simultaneous
      determination of Ch and ACh in rabbit brain tissue homogenates.

PMID- 14696932
TI  - Detection of 27 molecules in a single injection volume by Hadamard transform
      capillary electrophoresis.
AB  - A concentration detection limit of 100 fM was achieved for the fluorescein ion by
      improving the experimental setup used for Hadamard transform capillary
      electrophoresis. Two argon-ion lasers, a gating laser for sample injection and a
      probe laser for the excitation of analyte molecules, were employed for the
      efficient photodegradation of analyte molecules in laser-induced fluorescence
      detection using an optically gated sample-injection method. In addition, a
      dichroic mirror, located in the pathway of the probe laser was used to exclude
      the other lines of the argon-ion laser. Using a Hadamard matrix on the order of
      2046, the concentration limit of detection for fluorescein ion was determined to
      be 100 fM at S/N = 3, in which the average number of molecules in a single
      injection volume was calculated to be 27. The influences of the output power in
      both the gating and probe lasers on the sensitivity are also discussed.

PMID- 14696931
TI  - Bead-injection determination of total mercury in river water samples.
AB  - A bead-injection system is proposed for total mercury determination in river
      water samples. The procedure is based on the introduction of a defined quantity
      of a resin suspension in the flow system. The selected beads are packed inside of
      a flow cell and the formed resin mini-column constitutes the optical path. The
      sample volume is then selected, and its passage by the mini-column allows
      retention of the mercury ions on the surfaces of the beads. The introduction of a
      spectrophotometric reagent in the flow system leads to the formation of a colored
      Hg-dithizone complex on the surface of the bead, which is spectrophotometricaly
      monitored. The spent beads are directed to waste, allowing the system to become
      ready to process another sample. The proposed system handles about 20
      measurements per hour, consuming 1000 microl of the sample, 1 mg of Chelex 100
      resin and 1.25 microg of Dithizone per determination. When 1000 microl of the
      sample is injected, a linear analytical curve is obtained (A = 0.0052[Hg] +
      0.1028, from 0 up to 30 microg l(-1), R2 = 0.995); the detection limit is
      estimated to be 0.9 microg l(-1). The results are precise, r.s.d. < 9%; spiked
      sample recoveries within 91.2 and 109% are found.

PMID- 14696933
TI  - Determination of bisphenol A and 4-nonylphenol in human milk using alkaline
      digestion and cleanup by solid-phase extraction.
AB  - A highly sensitive and selective method based on alkaline digestion for the
      simultaneous determination of bisphenol A (BPA) and 4-nonylphenol (NP) was
      developed. The method consists of digestion of the matrix with ethanolic KOH,
      extraction with diethyl ether under a mild alkaline condition, cleaning with
      successive aminopropyl (NH2) cartridges and derivatization followed by a GC-MS
      analysis. The assay accuracies, expressed as recoveries, were 82 - 113% for BPA
      and 89 - 97% for NP. The limits of detection of BPA and NP were 0.09 ng/g and
      0.50 ng/g, respectively. The procedure will be reliable for the trace analysis of
      BPA and NP in human milk, since alkaline digestion can diminish their documented
      association with protein.

PMID- 14696934
TI  - Adhesion of gold nanoparticles on an electrochemically pretreated glassy carbon
      electrode.
AB  - This study describes a simple new method for the adsorption of gold nanoparticles
      on a glassy carbon (GC) electrode. By electrochemically oxidizing the GC
      electrode and immersing it into a gold colloidal solution, one could induce the
      adhesion of the gold nanoparticles. The image of the field emission scanning
      electron microscopy confirmed that the nanoparticles were evenly distributed over
      the surface. A 2-aminoethanethiol self-assembled monolayer was formed on the
      surfaces of the adsorbed gold nanoparticles and a reductive desorption wave was
      observed during the reduction of the adsorbed 2-aminoethanethiol.

PMID- 14696935
TI  - Electrocatalytic determination of L-ascorbic acid by modified glassy carbon with
      Ni(Me2(CH3CO)2[14]tetraenoN4) complex.
AB  - A novel modified glassy carbon electrode containing Ni(Me2(CH3CO)2[14]tetraenoN4)
      complex was used as an electrocatalytic sensor for the determination of L
      ascorbic acid in pH = 6.6. The peak potential shifted to negative by 205 mV
      compared with that for a bare electrode in cyclic voltammograms. The calibration
      curve was linear up to 6.2 x 10(-3) M with a detection limit 3.1 x 10(-7) M and
      an RSD% better than 2.47%. This newly modified electrode was applied to
      commercial pharmaceutical tablets, injections and foods. The obtained results
      were identical to those obtained by the classical 2,6-dichlorophenolindophenol
      method.

PMID- 14696936
TI  - Determination of repaglinide in pharmaceutical formulations by HPLC with UV
      detection.
AB  - A simple, precise and rapid RP-HPLC method was developed for the determination of
      repaglinide in pharmaceutical dosage forms. The method was carried out on a Shim
      pack, RP-C18 column using a mixture of methanol: 0.1% v/v triethylamine (pH
      adjusted to 7 with orthophosphoric acid) and detection was done at 235 nm using
      nimesulide as internal standard. The linearity range was 0.1 to 0.5 microg/ml.
      The intra-day and inter-day precision were in the range of 0.48 to 1.01 and 0.15
      to 1.15, respectively.

PMID- 14696937
TI  - Determination of trace amount of carbon disulfide in water by the
      spectrophotometric reaction-rate method.
AB  - Carbon disulfide (CS2) was determined at trace levels by its induction effect on
      the reaction of triiodide with azide in acidic media. The reaction was monitored
      spectrophotometrically by the decreased absorbance of triiodide over a period of
      30 - 180 s from the initiation of the reaction at 350 nm, with calibration linear
      range of 0.020 - 1.870 microg/ml CS2. The limit of detection is 0.013 microg/ml
      CS2. A carbon-active column was used for sample solution clean up. The proposed
      method was successfully applied to the determination of trace carbon disulfide in
      natural water.

PMID- 14696938
TI  - Automatic procedure exploiting multicommutation in flow analysis for simultaneous
      spectrophotometric determination of nonstructural carbohydrates and reducing
      sugar in forage materials.
AB  - A multicommutated flow procedure for simultaneous spectrophotometric
      determination of nonstructural carbohydrates and reducing sugar in forage
      materials is proposed. Determination of both analytes was based on the neucroine
      method after acid hydrolysis of nonstructural carbohydrates. Results for both
      analytes presented the following features: no significant difference at 90%
      confidence level when compared with reference method, linear response between 0.2
      to 0.8% (w/v) (r = 0.999); relative standard deviations of < 2.0% (n = 10), and
      sampling rate of 32 determinations per hour.

PMID- 14696939
TI  - Determination of nitrite by flow injection spectrophotometry using a home-made
      flow cell detector.
AB  - A simple, rapid, low cost and accurate determination using flow injection
      spectrophotometry with a home made flow cell detector, in combination with green
      LED and photodiode, had been developed for nitrite based on the Griess-Saltzman
      reaction, measuring the absorbance at 525 nm. The proposed system is able to
      monitor nitrite in freshwater samples at a throughput of 60 samples per hour with
      a relative standard deviation (%RSD) of less than 2.4% and a detection limit of
      <7 microg dm(-3). The calibration graph was linear between 0.010 - 1.0 mg dm(-3).

PMID- 14696940
TI  - Bladder cancer in Kano--a histopathological review.
AB  - Malignant tumours of the bladder have been observed to be quite common in Kano
      but there has been no formal study. This four-year (1998-2001) retrospective
      review sought to document the pattern of these neoplasms. Vesical malignancies
      constituted 6.4% of all cancers in Kano with squamous (53%) and transitional
      (35%) carcinomas as the most common histological types. Males outnumbered females
      more than five times (M:F = 5.2.:1). Cancer of the bladder was most prevalent in
      the 5th and 6th decades with a mean age of 48.8 years. In general our findings
      are similar to bladder cancer in other schistosomal endemic regions of Africa.

PMID- 14696941
TI  - The pattern of infertility cases at a university hospital.
AB  - Pattern of infertility cases attending the gynaecologic out patient clinic of
      Ogun State University Teaching Hospital, Sagamu Nigeria is presented. The
      incidence of infertility was found to be 14.8% with a mean duration of 3.38 +/-
      1.65 years. Secondary infertility predominated with 78.3% incidence. About three
      quarters (71.1%) were between 25 and 34 years of age and only 6.0% were below 25
      years of age Nullipara constituted majority of cases with 56.6%. Past history of
      induced abortion was significantly present in those with tubal blockage. Male
      factor only was the cause in 26.8%, female factor only in 51.8% and both male and
      female factors were contributory in 21.4% cases. The male partners refused semen
      analysis in about one third of cases (32.5%).

PMID- 14696942
TI  - Blepharoptosis in Ibadan, Nigeria.
AB  - OBJECTIVE: To look into the cases of blepharoptosis in our environment as well as
      find out the causes and effects of the ptosis. DESIGN: Prospective clinic study
      and prospective cluster sampling method of school children. SETTING: University
      College Hospital, Ibadan and 3 schools in Ibadan, Nigeria. SUBJECT: Over a 5 year
      period, all patients who presented with blepharoptosis at the University College
      Hospital were recruited for the study. During the same period, a school survey
      was also done to find out the prevalence of blepharoptosis among school children.
      RESULTS: Twenty five cases of blepharoptosis were found during the 5 year period.
      Fifty two percent of the patients were found to be less than 16 years of age
      while only 8% were over 50 years of age. There was a 1:1 male to female ratio
      with majority of them (68%) having only one eye affected. The most common cause
      of blepharoptosis was found to be congenital, accounting for 56% of the patients.
      The prevalence in the school survey was found to be 1.2% higher than the
      incidence of 0.5% found in the eye clinic. CONCLUSION: Blepharoptosis is not an
      uncommon ocular problem. A detailed assessment of the cause, amount of ptosis and
      levator functions helps to determine the most appropriate surgical technique
      which would give the best functional and cosmetic result.

PMID- 14696943
TI  - Pharmacological strategies in treatment-resistant depression.
AB  - Treatment-resistant depression may be due to factors such as co-morbid
      psychiatric or medical illnesses, chronic psychosocial stresses, and medication
      nonadherence. Alternative treatment strategies such as optimization, switching to
      a different antidepressant, augmentation or combination with another
      antidepressant are strategies useful in such patients. The first strategy in
      treating resistant depression is to optimize monotherapy. A switch should be made
      to another agent if there is no response to treatment after an adequate duration.
      Augmentation and combination strategies are useful if there is sub-optimal
      response to the initial antidepressant. With several antidepressants (selective
      serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase
      inhibitors and the newer antidepresssants) and various antidepressant
      augmentation and combination strategies available to clinicians, the outcome of
      treating patients with depression should improve.

PMID- 14696944
TI  - Comparing permanent tooth sizes (mesio-distal) of males and females in a Nigerian
      population.
AB  - Two hundred and fifty school children in Ibadan metropolis, comprising of 125
      male and 125 females were chosen by modified random sampling to study their tooth
      sizes (mesiodistal width) and to establish if there is any appreciable sex
      difference in their permanent tooth sizes. The teeth measured were selected based
      on certain criteria. The mesio-distal width of a tooth was recorded as the
      maximum distance between the tooth sides (proximal) of a tooth on a line parallel
      to the occlusal and buccal surfaces. The result showed that the male teeth were
      consistently larger than the female teeth. The summed total maxillary and
      mandibular arch width of the males were 3.31 mm and 1.37 mm greater than those of
      the females respectively. The differences in tooth size between males and females
      have been established.

PMID- 14696945
TI  - Forceps delivery at the University College Hospital, Ibadan, Nigeria.
AB  - The incidence of forceps delivery has reduced in Nigeria and in the world in
      general. Some Obstetricians have not been trained in its use and lack the skill.
      OBJECTIVE: To determine the outcome of forceps delivery at this centre.
      METHODOLOGY: A retrospective analysis of all forceps delivery done at this centre
      between the 1st of January 1997 and 31st December 2001, a 5-year period was done.
      RESULTS: The incidence of forceps delivery was 1.57% or 16 per 1000 births and
      they were all low cavity deliveries. Most of the patients (68.5%) were booked at
      this centre. The mean age was 28.21 +/- 4.79 years and most (64.4%) were
      nulliparious. The mean gestational age at delivery was 38.7 +/- 3.0 weeks. The
      most common indications were prolonged second stage of labour (58.9%), maternal
      distress (43.8%) and fetal distress (15.1%). There were multiple indications in
      some patients. The mean birth weight was 3.03 +/- 0.69 kgs and 90.4% were live
      births. The main maternal complications were maternal injuries (8.1%), primary
      post partum haemorrhage (5.5%), anaemia (5.5%) and retained products of
      conception (4.1%). Maternal deaths occurred in 2 eclamptics and birth asphyxia in
      6.9% of babies. The perinatal mortality rate was 54.8 per 1000 births. There were
      no fetal injuries. CONCLUSION: Obstetrics forceps delivery is on the decline in
      Nigeria. It is an art that can safely and quickly deliver the fetus. It could be
      offered in the place of a caesarean section in some instances with a good outcome
      to both the mother and fetus in skilled hands. Obstetricians should be trained to
      use it more frequently.

PMID- 14696946
TI  - Psychosocial factors associated with perceived psychological health, perception
      of menopause and sexual satisfaction in menopausal women and controls.
AB  - OBJECTIVES: The study investigated factors associated with attitude towards sex
      role, self-image and marital satisfaction on psychological health status,
      perception of menopause and sexual satisfaction in climacteric women in Ibadan,
      Nigeria. SUBJECTS AND METHODS: 45 female participants were randomly selected from
      Ibadan. The mean age was 51.42 +/- 8.05 years (range = 36 - 70 years). The mean
      age for the 13 non-menopausal women was 42.79 +/- 3. 91 years (range = 42 - 47
      years) while the mean age for the 32 menopausal women was 5.16 +/- 6.08 years
      (range = 47 - 70 years). The mean age of the children of the participants was
      16.05 +/- 8.09 years (range = 1 - 36 years). A questionnaire having several
      subsections (consisting of the psychological health status of women in the
      climacteric, attitude towards sex role, perception of menopause, social support,
      marital satisfaction, self-image and sexuality scales was used for the
      assessment. RESULTS: Post-Menopausal women reported better psychological health
      compared to the pre-menopausal women (t = 1.86, p < .05) but no significant
      differences in their attitude to sex role. Post menopausal women had more
      positive attitude to sex (t = 3.15, p < .01) and were more knowledgeable about
      menopause (t = 2.15, p < .03). Women with conservative/reactionary preference for
      traditional sex roles reported negative perception of menopause compared to those
      with liberal attitude toward sex role (t = 1.82, p < 0.05). Menopausal Status,
      Educational level and social support predicted positive attitude to sex, (F =
      3.62, P < .01). Age, self-image and attitude to sex domain of the marital
      satisfaction scale predicted better psychological health, and marital cordiality
      predicted better psychological health as measured by GIIQ (R2 = 25, beta = -43, t
      = -2.38, P < .02). Marital satisfaction significantly predicted better sexuality,
      (F = 5.47, R square = 0.11, p <0.05). Sources of information on menopause
      included health institutions, books, doctors, and books/health workers.
      CONCLUSION: The study highlights the need for sensitizing menopausal Nigerian
      women on how to improve their self-image, marital satisfaction, and sexual
      satisfaction. Conventional treatment options emphasizing hormone replacement
      therapy, need for nutritional supplement, dietary changes, marital and sex
      therapy are emphasized.

PMID- 14696947
TI  - Primary caesarean section in nulliparous and grandmultiparous Saudi women from
      the Abha region: indications and outcomes.
AB  - OBJECTIVE: To assess the indications for and outcomes of primary caesarean
      section (PCS) perfomed in nulliparous and grandmultiparous women in the Abha
      region of Saudi Arabia. METHODS: A retrospective cohort study. MATERIALS: 393
      nulliparous women (para 0) (NPG) and 432 grandmultiparous women (parity>5) (GMPG)
      who had PCS at the Abha Maternity Hospital (AMH) over a 3-year period, (1997
      1999) formed the basis of the study. RESULTS: The PCS rates in NPG and GMPG were
      19.4% and 18.3% respectively with no statistically significant difference.
      (p>0.05). There were statistically significant differences between the two groups
      regarding the mean age, blood loss during surgery, post operative haemoglobin,
      and birth weight were compared, p<0.05. There was no statistically significant
      differences in the mean gestation at delivery, p>0.05. The most common indication
      for surgery in the two groups of patients was fetal distress (NPG=28%, GMPG=25%:
      p=NS), followed by failure of progress in labour. (NPG=22.7%, GMPG =21.6%, p=NS).
      Antepartum haemorrhage (APH) was the indication for PCS in 6.8% of the NPG and
      13.9% of the GMPG, (p<0.05). Multivariate linear regression analysis indicated
      that maternal age and booking status significantly affected birth weight
      (p=0.004,p=0.022 respectively). However, neither birth weight nor low Apgar score
      was affected by the indications for CS or parity. While there were no perinatal
      deaths in the series, no statistically significant difference was found between
      the two groups with regards to low Apgar score (<7 at 5 mins), p>0.05.
      CONCLUSION: The major indications for PCS were the same in the NPG and GMPG in
      our study while the CS rates were similar in both groups. However, APH and its
      inherent complications occured more commonly in the GMPG. Neonatal morbidity was
      similar in both groups of women, but the mean birth weight was significantly
      higher in the GMPG. However, in order to reduce the high CS rate in these groups
      of patients, and in our obstetric population in general, it is suggested that CTG
      be used appropriately in high risk women and that intermittent auscultation is
      recognized as a valid form of management for most low risk cases.

PMID- 14696948
TI  - Uterine rupture: UCH, Ibadan experience.
AB  - OBJECTIVES: To determine the incidence, predisposing factors, maternal and fetal
      outcome of uterine rupture patients at the University College Hospital (U. C.
      H.), Ibadan. MATERIALS AND METHODS: A 5-year retropective study of patients with
      uterine rupture in U. C. H., Ibadan between January 1996 - December, 2000 was
      done. RESULTS: Thirty five cases of uterine rupture out of a total delivery of
      4531 were recorded over the 5-year period. An incidence of 7.75/1000 deliveries
      or 0.72% was obtained and the yearly trend showss it's on the increase. 85.7% of
      the patients were unbooked. Common modes of presentation were bleeding per
      vaginam and abdominal pain. Spontaneous cause of rupture predominates. The
      interval between diagnosis and surgery was greater than 7 hours in 75% of cases.
      Uterine repair with or without tubal ligation was commonly employed. Case
      fatality rate was high at 17.9%. Perinatal mortality was 92.5%. Other maternal
      morbidities include anaemia, puerperal and wound sepsis, vesico-vaginal fistula
      and prolonged hospital stay. CONCLUSION: All the indice at the present time are
      higher than they were 10 years ago. The incidence is still high and is on the
      increase. Attributable reasons include type I, II, III delays in health care
      service utilization associated with poor socioeconomic status of patients and
      lack of essential drugs and compatible blood in the hospitals.

PMID- 14696949
TI  - Lupus anticoagulant in Nigerian women with preeclampsia.
AB  - OBJECTIVE: The Lupus Anticoagulant (LA) which used to be known for its
      interference with coagulation studies in the 1950s, has now been recognised to be
      associated also with diverse disease conditions in the developed countries. Our
      aim therefore was to determine the prevalence of the lupus anticoagulant (LA) in
      women with pre-eclampsia and controls. SUBJECT AND METHODS: A total of seventy
      six pregnant women, were studied, twenty-six pre-eclampsia and fifty who were
      apparently healthy served as controls. The Kaolin clotting time test (KCT) was
      performed in duplicates on plasma samples from subjects and controls. Mixing
      ratio was calculated in order to determine the presence of the lupus
      anticoagulant, Kaolin clotting time ratio of greater than or equal to 1.2 was
      taken to signify the presence of the lupus anticoagulant. RESULTS: Eleven (42.3%)
      of the women with pre-eclampsia had prolonged KCT as against 2(4%) of the
      pregnant control. The clotting time of 7 of the '11 pre-eclampsia with prolonged
      KCT, were correctd by normal plasma, while 4 were not corrected. The KCT ratio of
      all 4 were greater than 1.2 signifying the presence of LA (15.4% prevalence). One
      (2%) of the pregnant control had KCT ratio greater than 1.2 (2%) prevalence of
      LA). CONCLUSION: A number of Nigeria women with pre-eclampsia also have the lupus
      anti-coagulant therefore African women with pre-eclampsia should be screened for
      the presence of lupus anticoagulant.

PMID- 14696950
TI  - Pattern of semen analysis of male partners of infertile couples at the University
      College Hospital, Ibadan.
AB  - OBJECTIVES: To evaluate the seminal patterns of the male partners of the
      infertile couples, towards identifying the possible contribution of the male
      factors to overall infertility problem in our environment. METHODOLOGY: The study
      is a descriptive analysis of the seminal patterns of the partners of the
      infertile couples, who presented at the Fertility Research Unit (a WHO
      collaborating centre) of the Department of Obstetrics and Gynaecology, University
      College Hospital, Ibadan, Nigeria, between 1st January 1990 and 31st December,
      1999. RESULTS: Result of the seminal analysis of 824 male partners of infertile
      couples were retrieved for the study, of which 598 (73%) were referred for
      secondary infertility. Overall, 225 (27.3%) of these subjects had abnormal semen
      analyses, with Asthenozoospermia being the most common (27.8%) of the disorders
      observed. Fifty-four (6.7%) subjects of the study population had Azoospermia. The
      most common multiple factors abnormality in the study population was
      Astheno/Oligozoospermia (25.5%), while three factors defect-
      Oligo/Astheno/Teratozoospermia was noticed in 106 (13.1%) of the subjects.
      CONCLUSION: Abnormal semen quality remains a significant contribution to overall
      infertility in our environment and Asthenozoospermia is the most common seminal
      quality abnormality.

PMID- 14696951
TI  - Correlation of electrocardiogram with echocardiographic left ventricular mass in
      adult Nigerians with systemic hypertension.
AB  - Systemic hypertension, High Blood Pressure (HBP) is common in Nigeria with up to
      10 to 15% prevalence among adults. HBP is readily complicated by left ventricular
      hypertrophy (LVH), recognised to herald a series of adverse outcomes in
      cardiovascular health. In order to device a method of assessment of LVH that is
      objective, readily available, affordable and easily operable in the face of
      soaring cost of the more recent techniques, correlation of electrocardiographic
      (ECG) LVH parameters was done with echocardiographic (ECHO) left ventricular mass
      (LVM). ECG is objective, affordable and easily operable, while ECHO is highly
      accurate for measurement of LVM. One hundred and fifty-five hypertensives were
      studied (123m; 32f). A statistically significant correlation was found with a
      maximum coefficient of 0.36 in males only. ECG can thus offer an objective
      alternative for assessment of LVH in HBP in males where ECHO is not available or
      practicable.

PMID- 14696952
TI  - Interference by malaria in the diagnosis of typhoid using Widal test alone.
AB  - A total of 270 febrile patients (130 males and 140 females) aged between 15 and
      59 were screened using thick and thin blood film stains for malaria,
      bacteriologic culture and Widal test for enteric fevers. Sixty (22%) were
      positive for malaria while 38 (14%) were positive for enteric fevers out of which
      16 (26.6%) concomitantly had malaria parasite. Cases without malaria parasite
      (MP) or enteric fever organism were 172 (63.7%) and classified as pyrexia of
      unknown origin (PUO). Forty-four were strictly malaria cases out of which 36
      (82%) were due to Plasmodium falciparum, and all had antibody Widal titres > or =
      160 to 0 antigen while 4 (9%) were due to Plasmodium malariae, 3 (6.8%) were due
      to P. ovale and 1 (2.3%) was due to P. vivax. Twenty (52.6%) of the 38 patients
      with enteric fever had typhoid, all had Widal titres > or = 160 to 0 antigen. In
      all, antibody reaction Widal titres to H antigen were < 20. There was no
      statistical significant difference [chi2 = 327.2, P > 0.05] between Widal titres
      of malaria and typhoid cases. Hence using Widal test alone, one cannot
      differentiate typhoid fever from malaria. In another 250 healthy adults, of equal
      sex distribution, used as controls 12 (4.8%) had malaria parasite and 4 (1.6%)
      had enteric fever organisms. While only 4 (1.6%) gave Widal titre of 80 to 0
      antigen the rest had antibody titres of < 20 to O antigen. Malaria could
      interfere with serological diagnosis of typhoid and hence lead to over diagnosis
      of typhoid in Nigeria.

PMID- 14696953
TI  - Standard 12 lead and 24 hour Holter electrocardiographic observation in a
      biracial group of perinatally asphyxiated newborns.
AB  - AIM: To compare the cardiovascular responses to perinatal stress between two
      ethnic groups of newborns. STUDY POPULATION: 23 Nigerians and 14 Dutch perinally
      asphyxiated newborns together with their respective control of 12 healthy
      Nigerian and 16 Dutch newborns. METHOD: The study subjects and their controls
      were evaluated with standard 12-lead and 24-hour Holter electrocardiographic
      recordings within 36 hours of postnatal life. RESULT: Rhythm, rate, P-wave, P-R
      interval and QRS duration were normal in study subjects and their respective
      controls on standard ECG. The prevalence of ST-segment depression in the mid
      precordial lead V4 was significantly higher in the asphyxiated Nigerian infants
      (78%) than in the controls (42%); p < 0.05. Similarly, its prevalence in the
      Dutch infants (50%) was significanly different from the zero prevalence in the
      Dutch controls; p < 0.05. Long duration ECG recordings showed a 'fixed heart
      rate' phenomenon in the asphyxiated infants but not in their controls.
      CONCLUSION: ST-segment depression may imply myocardial ischaemia in asphyxiated
      Dutch newborns but such may not be inferred in asphydiated Nigerian newborns.
      'Fixed heart rate' phenomenon or loss of sinus arrhythmia appears to be causally
      related to hypoxaemia which results from perinatal asphyxia.

PMID- 14696954
TI  - A report of the consultative meeting and workshop for strengthening African
      Medical Journals. Salle A, WHO/HQ, Geneva 14 - 16 October, 2002.

PMID- 14696955
TI  - Your brother: Charles R. Drew, M.D., FACS an American surgeorn with Roman
      virtues.

PMID- 14696956
TI  - Unusual causes of acute abdomen in a Nigerian hospital.
AB  - Acute abdomen is the most common abdominal emergency associated with high
      morbidity and mortality in General surgical practice. Over a 7-year period, a
      study of unusual causes of acute abdomen was undertaken, with the aim of
      identifying these causes and outcome of operative management. Eleven cases were
      identified accounting for 4% of cases of acute abdomen seen during the period of
      the study. Four cases of liver diseases (33.3%) comprising 2 patients (16.7%)
      with ruptured primary liver cell carcinoma, 1 (one) case each of haemoperitoneum
      due to ruptured liver haemangioma and haemorrhagic disorders from liver
      cirrhosis. One patient had acute leukaemia with massive haemoperitoneum and acute
      abdomen. Five (45.5%) had gastrointestinal perforations; 1 patient (9%) each had
      multiple jejunal perforations, perforation of stomal ulcer at gastrojejunostomy
      site, perforation of gastric cancer; perforated carcinoid tumour of sigmoid colon
      and idiopathic perforation of the caecum. There was also a case of caecal
      volvulus. Mortality was 7 patients (63.6%). All patients with liver pathology and
      acute leukaemia died. The cases of malignant tumour perforation were well and
      alive 4-6 years after the operation. CONCLUSION: Operation could have been
      avoided in 45.5% of these cases if the appropriate investigations, had been
      available and carried out.

PMID- 14696957
TI  - Infective lumbar discitis in a sickler--an occult 'typhoid' spine?
AB  - Pyogenic infection of the intervertebral disc (discitis) is a rare infection and
      the diagnosis often depends on a high index of suspicion. The cases of infective
      discitis described in the modern literature are similar to, if not identical with
      what was described as 'typhoid spine'. Salmonella infection of the
      musculoskeletal system on the other hand is more common in patients with sickle
      cell anaemia. This case report highlights the bizarre presentation of infective
      lumbar discitis in a sickler (HbSS) and calls attention to the need for a
      thorough evaluation of low back pain in these patients.

PMID- 14696958
TI  - In vitro studies with the calcimimetic, cinacalcet HCl, on normal human adult
      osteoblastic and osteoclastic cells.
AB  - This study examined whether the calcium-sensing receptor (CaR) is expressed in
      normal adult human osteoblastic and osteoclastic cells in culture, and whether
      the calcimimetic, cinacalcet HCl (AMG 073), potentiates the effects of calcium
      (via CaR, or some other receptor/mechanism). When mouse or human osteoblastic
      cells were treated with higher concentrations of calcium (6.6 or 8.6 mM in alpha
      MEM/10% FBS) than present in control cultures (1.6 mM), the previously well
      documented increase in cell number was demonstrated. Cinacalcet HCl affected cell
      proliferation of CHO cells transfected with CaR, dose dependently, but had no
      effect on human or mouse osteoblastic cell proliferation in calcium-containing
      medium (1.6 or 8.6 mM). To test cinacalcet HCl and calcium on osteoclastic cells,
      peripheral blood mononuclear cells were cultured in medium containing RANK ligand
      and M-CSF, supplemented with calcium, and/or cinacalcet HCl. Tartrate-resistant
      acid phosphatase-positive multinucleated osteoclastic cells on plastic or bone
      were then counted at 11 and 21 days, respectively. Calcium (greater than 6.0 mM)
      inhibited osteoclast formation, but cinacalcet HCl (30-1000 nM) had no effect on
      osteoclastic formation or resorption in the presence of calcium (1.6 or 6.1 mM).
      RT-PCR did not detect CaR in human, rat, or mouse primary osteoblastic cells and
      cell lines or osteoclastic cells. In conclusion, these studies indicate that the
      calcium-induced increase in osteoblastic cell number, and the decrease in
      formation/function of osteoclastic cells, involves a mechanism or receptor other
      than CaR. In addition, the calcimimetic agent did not potentiate the effects of
      calcium on normal adult human bone cells in vitro.

PMID- 14696959
TI  - In collaboration: the Jackson Laboratory Craniofacial Resource.
AB  - Dr. Sandy C. Marks, Jr., has been a longtime collaborator of the Mouse Mutant
      Resource at The Jackson Laboratory and, most recently, was involved in the
      development of a Craniofacial Resource at TJL. The goals of this resource are to
      discover and supply to the scientific community mouse models of human
      craniofacial disease. A brief description of this collaboration is presented in
      Sandy's honor.

PMID- 14696960
TI  - Mineral changes in osteopetrosis.
AB  - Bones of animal models of osteopetrosis in a variety of animal species are
      characterized by increased density but impaired mechanical properties. Analysis
      of mineral properties by several physical-chemistry techniques has shown that the
      crystals in the hyper-mineralized bones are smaller and less perfect than those
      in age-matched normal animals. Here we review the data on mineral crystal changes
      in osteopetrosis and the techniques for determining these properties, and suggest
      that the small crystal size contributes to the bones' altered mechanical
      properties.

PMID- 14696961
TI  - The effects of colony-stimulating factor-1 (CSF-1) on the development of
      osteoclasts and their expression of tartrate-resistant acid phosphatase (TRAP) in
      toothless (tl-osteopetrotic) rats.
AB  - The osteopetrotic mutation toothless (tl) in the rat is characterized by a
      limited number of osteoclasts with reduced amounts and/or activity of tartrate
      resistant acid phosphatase (TRAP). Treatment of tl/tl mutants with the cytokine
      colony-stimulating factor (CSF)-1 increases both osteoclast number and enzyme
      activity, consistent with a loss-of-function mutation in the CSF-1 gene recently
      detected in this mutant. We have pursued these observations to demonstrate that
      there is a dose-dependent increase in osteoclast number, but not to normal
      levels. Osteoclasts in CSF-1-treated tl/tl mutants are large, have well-developed
      clear zones and ruffled borders, and secrete TRAP into resorption lacunae. The
      expression of TRAP mRNA, protein, and enzyme activity per bone appear normal
      after CSF-1 treatment. However, in contrast to the predominantly apical
      intracellular distribution in normal osteoclasts, an enrichment of TRAP enzyme
      activity in osteoclasts of CSF-1-treated tl/tl mutants is observed in the basal
      part of the cell. Our observations suggest that the CSF-1-treated mutant bones
      contain an abundance of mature osteoclasts, actively expressing markers for
      osteoclasts such as TRAP, cathepsin K, and matrix metalloproteinase (MMP)-9.
      Accumulation of TRAP at the end of the endocytic pathway in mature osteoclasts
      formed during CSF-1 treatment suggests that the TRAP enzyme has a rapid turnover
      in these highly active cells and uses a transcytotic pathway.

PMID- 14696962
TI  - Gap-junctional regulation of osteoclast function.
AB  - Previous research has shown that bone-resorbing osteoclasts contain connexin
      molecules that organize to hemichannel-forming connexons, which in turn form
      functional gap junctions in neighboring cells. So far only little is known about
      the role of gap junctions in osteoclasts. However, blocking of the gap-junctional
      communication inhibits bone resorption in vitro. Knockout mice deficient of
      Connexin-43, the major connexin in bone cells, show surprisingly little skeletal
      manifestations. Gap-junctional communication in osteoblasts and osteocytes is
      well documented and seems to be essential for the integrity of bone cells, as
      well as for the transfer of mechanical signals of bone loading. The role of gap
      junction in osteoclasts is unclear, so far, but some putative roles have been
      suggested, including their participation in osteoclast precursor fusion to
      multinucleated mature osteoclasts, communication in the bone multicellular unit
      in bone remodeling, osteoclast survival, and apoptosis.

PMID- 14696963
TI  - Osteoblast precursors at different anatomic sites.
AB  - Skeletal morphology depends on the local regulation of bone formation, both in a
      quantitative and qualitative sense. The formative cells, osteoblasts, adjust
      their synthetic activity in response to signals that influence cell
      differentiation and matrix production. Here, we review data concerning the
      morphological patterning during bone ontogenesis and its direct cause:
      osteoblasts at specific anatomic sites. An overview of the possible origins of
      osteogenic cells is presented, considering bone growth and homeostasis, and
      discussing the repair process. A testable model is proposed, in which functional
      differences between osteoblast populations are explained by homeobox-gene
      regulation. Newly developed markers for osteoblast recruitment and
      differentiation provide an experimental system to test the impact of homeobox
      gene expression on osteoblast differentiation and bone matrix production.

PMID- 14696964
TI  - Serum levels of TGF-beta and fibronectin in autosomal dominant osteopetrosis in
      relation to underlying mutations and well-described murine counterparts.
AB  - The study gives a further biochemical description of two different forms of
      autosomal dominant osteopetrosis (ADO) in relation to murine counterparts, with
      special attention to osteoblast function and the recent discovery of LRP5 gene
      mutations in ADO I. Patients and controls were investigated for markers of bone
      formation and resorption at baseline and following stimulation with thyroid
      hormone. Moreover, four different well-described murine models of osteopetrosis
      were investigated. Concerning the human forms, serum TSH levels decreased in all
      subjects, indicating effects on the target tissue. Osteocalcin and cross-linked
      collagen (NTx) were without significant differences among the groups. Significant
      increases in both markers were seen following stimulation. Baseline active TGF
      beta1 levels were increased in both types of ADO (60% in ADO I [P = 0.006]; 46%
      in ADO II [P = 0.001], respectively), whereas fibronectin levels were decreased
      in both (ADO I 58% and ADO II 63% of normal, respectively [P = 0.012 and P =
      0.001]). Following treatment, levels increased temporarily in all groups. In the
      murine models, active TGF-beta1 was significantly decreased in the tl- and ia
      rat, whereas fibronectin levels were decreased in the mi-mouse, however,
      increased in the ia-rat. In conclusion, both types of ADO showed the same
      qualitative biochemical differences compared to controls, except that OPG levels
      were higher in ADO I. The decreased fibronectin levels in both types and in
      murine models reflect decreased bone resorption; however, this may also indicate
      hitherto unrecognized alterations in bone formation. Biochemical differences
      among known syndromes related to mutations in the LRP5 gene indicate different
      underlying pathogenetic mechanisms.

PMID- 14696965
TI  - Expression of vascular endothelial growth factor in the dental follicle.
AB  - Tooth eruption requires the presence of the dental follicle to recruit
      mononuclear cells, which fuse to form osteoclasts that resorb the alveolar bone
      such that the tooth can erupt. In the rat first mandibular molar, there is a
      major burst of osteoclastogenesis at day 3 postnatally and a lesser burst at day
      10. Eruption molecules, such as CSF-1, are maximally expressed at day 3 in the
      dental follicle to promote this maximal osteoclast formation, but by the time of
      the secondary burst of osteoclastogenesis their expression is dramatically
      reduced. Because vascular endothelial growth factor (VEGF) can substitute for CSF
      1 to promote osteoclastogenesis, we examined its gene expression in vivo in the
      dental follicle and found that it and its two major isoforms (VEGF 120 and 164)
      were all maximally expressed at days 9-11, the time of the secondary burst.
      Treatment of the cells with phorbolmyristate acetate (PMA), a protein kinase C
      (PKC) activator, enhanced expression of the 2 major VEGF isoforms in the cultured
      dental follicle cells, whereas adding a specific PKC inhibitor prevented this.
      Treatment with PMA also increased the protein level of VEGF. Thus, VEGF may be
      involved in promoting the secondary burst of osteoclastogenesis, and activation
      of PKC may upregulate its expression.

PMID- 14696966
TI  - Perspective. Osteoclastogenesis and growth plate chondrocyte differentiation:
      emergence of convergence.
AB  - A "bone" is really a dynamic and highly interactive complex of many cell and
      tissue types. In particular, for the majority of skeletal elements to develop and
      grow, the process of endochondral ossification requires a constantly moving
      interface between cartilage, invading blood vessels, and bone. A great deal has
      been learned in recent years about the regulation of chondrocyte proliferation
      and differentiation by hormones, growth factors, and physiologic stimuli during
      skeletal development and growth. Likewise, the discovery that colony stimulating
      factor-1 (CSF-1, or M-CSF) and receptor activator of NF-kappaB ligand (RANKL, a
      tumor necrosis factor superfamily member also called TRANCE, ODF, OPGL, and
      TNFSF11) are pivotal in communicating from osteoblasts to osteoclasts has led to
      deeper insights into bone growth, turnover, and maintenance. Little is known,
      however, about how these two quite different systems communicate to solve the
      problem of providing integrated, continuous mechanical support during the dynamic
      invasion of cartilage by bone that characterizes endochondral bone growth.
      Evidence has accumulated in recent years that provides insight into the
      communication between growing bone and cartilage in the form of a subset of
      osteopetrotic mutations, which share a lack of osteoclasts and an accompanying
      chondrodysplasia of the growth plate. These mutations thus implicate some of the
      same gene products in regulating chondrocyte differentiation and bone resorption.
      We also consider expression studies of some known growth plate regulators, such
      as parathyroid hormone-related protein (PTHrP) and Indian hedgehog (Ihh), in
      light of this and propose a model in which the osteoclastogenic factors act also
      on chondrocytes, but downstream of PTRrP and Ihh in regulating proliferation and
      differentiation, and after early morphogenic patterns are established.

PMID- 14696967
TI  - Growth hormone receptor and insulin-like growth factor-I immunoreactivity in
      osteoclast-like cells during tooth eruption in the toothless (osteopetrotic) rat
      following treatment with colony-stimulating factor-1.
AB  - In the toothless (tl/tl) osteopetrotic rat, teeth form but fail to erupt.
      Treatment of tl/tl rats with colony-stimulating factor-1 (CSF-1) activates bone
      resorption by osteoclasts, permits tooth eruption, and up-regulates the
      immunoreactivity of bone marrow mononuclear cells to growth hormone receptor
      (GHr) and insulin-like growth factor (IGF)-I. This study examined the
      distribution of tartrate-resistant acid phosphatase (TRAP) and immunoreactivity
      for GHr and IGF-I in osteoclast-like cells located on the alveolar bone margin,
      adjacent to the lower first molar crown, in 14-day-old normal and tl/tl rats,
      following treatment with CSF-1. Osteoclast-like cells demonstrated a positive
      reaction for TRAP, GHr, and IGF-I in all groups. However, in tl/tl tissue,
      osteoclast-like cells were generally negative for GHr. There was no significant
      difference in the total number of TRAP-, GHr-, and IGF-I-positive osteoclast-like
      cells on the adjacent bone margin in normal, normal treated with CSF-1, and tl/tl
      rats. CSF-1 treatment of the tl/tl rat significantly increased the total number
      of osteoclast-like cells, which were positive for TRAP (p < 0.001), GHr (p <
      0.05) and IGF-I (p < 0.01).

PMID- 14696968
TI  - Identification and characterization of the genes encoding human and mouse
      osteoactivin.
AB  - Osteoactivin (OA) is more highly expressed in the bones of osteopetrotic mutant
      rats (op/op) than in those of their normal littermates and is the homologue of
      human nmb, a cDNA more highly expressed in melanoma-derived cell lines of low
      metastatic potential, and of mouse DC-HIL, which has been implicated in
      endothelial cell adhesion. The human OA gene is found on chromosome 7p15.1 and
      consists of 11 exons spanning 28.3 kb. Murine OA is encoded by a highly similar
      gene of 11 exons spanning 20.2 kb on mouse chromosome 6. Human OA uses the same
      transcriptional initiation site in both bone and kidney as was reported for
      melanoma cells. OA is expressed in primary human and mouse osteoblast cultures at
      all stages of differentiation, with increased levels observed concurrently with
      the expression of osteoblast phenotype markers. OA is also expressed in a wide
      variety of human and mouse tissues as determined by RT-PCR analysis.
      Immunohistochemical investigation of OA expression in late mouse embryonic
      development showed very high, cell-specific expression in the nervous system,
      basal layer of the skin, germinal cells of hair follicles, and in the forming
      nephrons of the kidney. Continuing investigation of the cell-specific expression
      of OA in bone as well as in other tissues will lead to a better understanding of
      its function in the development of these cell types.

PMID- 14696969
TI  - Role of apoptosis in glucocorticoid-induced osteoporosis and osteonecrosis.
AB  - Bone disease is a side effect of concern regarding chronic glucocorticoid (GC)
      administration. Most GC-treated patients exhibit a process of bone loss,
      frequently leading to osteoporosis, with increased fracture risk, especially in
      spinal vertebrae. Some GC-treated patients will develop osteonecrosis, a disease
      with distinct clinical and histopathological features, most often occurring
      underneath the articular surface of the femoral head. Remarkably, both of these
      GC-induced bone diseases are associated with osteoblast and osteocyte apoptosis,
      which is emerging as a potential primary pathogenic mechanism. Here, we review
      the evidence for osteoblast and osteocyte apoptosis in GC-induced bone disease
      and highlight current debates: (1) With recent reports describing the
      antiapoptotic effect of GCs in some in vitro osteoblast models, and with the
      known adverse effects of GCs on osteoblast cell cycle and differentiation, could
      the in vivo osteoblast apoptosis be an indirect rather than a direct effect of
      GCs? (2) What is the pathogenic relationship between GC-induced osteoporosis and
      osteonecrosis? Could the latter be a mere manifestation of the former? and (3)
      How does apoptosis fit into the traditional concept of ischemia as a key etiology
      in osteonecrosis? Regardless of the answers, recent studies with cells, animals,
      and humans point out bone cell apoptosis as a potential target in the design of
      treatment for GC-induced bone disease.

PMID- 14696970
TI  - P2 receptors in bone--modulation of osteoclast formation and activity via P2X7
      activation.
AB  - The concept that adenosine triphosphate (ATP) can act as an extracellular
      signaling molecule via interactions with specific purinergic receptors to mediate
      a wide variety of processes as diverse as neurotransmission (Edwards et al.,
      1992), inflammation (Perregaux et al., 1994), apoptosis (Chow et al., 1997), and
      bone remodelling (Jones et al., 1997; Morrison et al., 1998) is now widely
      accepted. Since the early work of Burnstock (Burnstock, 1972), the number of
      characterized P2 receptors responsive to extracellular nucleotides has increased
      dramatically. It is now known that both osteoblasts and osteoclasts express
      multiple P2 receptor subtypes, and the increasing number of nucleotide-induced
      effects reported to occur in bone serves to highlight the importance of these
      receptors in the bone microenvironment and the bone remodeling processes. In this
      article we will review work from our laboratory, and others, that has established
      nucleotides and P2 receptors as important signaling molecules in bone. In
      particular, we will focus on the expression of P2 receptors by osteoclasts and,
      more specifically, the P2X7 receptor and its paradoxical role in osteoclast
      function.

PMID- 14696971
TI  - Multinucleated osteoclast formation in vivo and in vitro by P2X7 receptor
      deficient mice.
AB  - The P2X7 receptor is a member of the family of P2X purinergic receptors, which
      upon sustained activation forms large pores in the plasma membrane. In cells of
      hematopoietic origin, P2X7 receptor activation has been shown to lead to multiple
      downstream events, including cytokine release, cell permeabilization, and
      apoptosis. This receptor has also been implicated in the generation of
      multinucleated giant cells, polykaryons, and osteoclasts. We have recently
      demonstrated that a blockade of this receptor inhibits osteoclast formation in
      vitro; therefore, we examined mice deficient in the P2X7 receptor in the context
      of bone. These mice were healthy and displayed no overt skeletal problems.
      Furthermore, we were able to demonstrate their ability to form multinucleated
      cells, in particular osteoclasts, both in vivo and in vitro. We also demonstrate
      the ability of P2X7R-/- multinucleated osteoclasts, upon stimulation with
      maitotoxin (MTX), to form pores in the plasma membrane in vitro. These findings
      are consistent with the existence of an endogenous pore structure present in
      osteoclast precursor cells that can be activated either by the P2X7 receptor, or
      in its absence, by alternative signals to mediate fusion and pore formation.
      These data provide further insight into the mode of action of the P2X7 receptor.

PMID- 14696972
TI  - Prostaglandin E--a powerful anabolic agent for generalized or site-specific bone
      formation.
AB  - Prostaglandins are locally secreted, rapidly metabolized, biologically active
      fatty acids first identified in the prostate. The role of prostaglandins in the
      inflammatory response has been widely studied. However, some prostaglandins,
      particularly those of the E series (PGEs), can suppress inflammation, making it
      difficult to understand the local events and their sequence. This bimodal
      potential of the PGEs has been poorly understood in skeletal biology, causing the
      initial report of PGEs as mediators of bone resorption to persist for more than
      two decades, despite ample evidence to the contrary. This resulted in part from
      the power of any initial report to overrule subsequent conflicting views and in
      part on the exclusive reliance on in vitro data to explain in vivo phenomena.
      Over a decade ago, the potential of PGEs as authentic anabolic skeletal agents
      was demonstrated convincingly in vivo by both systemic and local delivery. The
      potential clinical applications of the PGEs in skeletal biology have not yet been
      developed. Our purpose is to review the reasons for the delayed discovery of the
      true skeletal effects of the PGEs and to describe applications for this
      technology. With the development of appropriate delivery systems, one can
      anticipate widespread clinical applications of the PGEs to accelerate skeletal
      repair, and to treat skeletal pathologies and trauma.

PMID- 14696973
TI  - Anti-osteoactivin antibody inhibits osteoblast differentiation and function in
      vitro.
AB  - Osteoactivin (OA) is a novel protein identified by mRNA differential display
      using bone from osteopetrotic versus normal rats. Bioinformatic analysis showed
      that OA cDNA has an open reading frame of 1716 bp encoding a protein of 572 aa,
      the first 21 aa constitute a signal peptide. OA sequence analysis also
      demonstrated 13 putative N-glycosylation sites suggestive of a heavily
      glycosylated protein. In this study, we localized OA protein in primary
      osteoblast culture by immunofluorescent staining and Western blot analysis.
      Primary osteoblast cultures pass through three stages: proliferation from day 1
      to 7, matrix formation from day 7 to 14, and matrix mineralization from day 14 to
      21. OA protein was detected at all stages examined, with maximal expression at 3
      weeks when osteoblasts are terminally differentiated. Using the Chariot
      transfection reagent as a vehicle to deliver anti-OA antibody into the cells, we
      demonstrated that anti-OA antibody significantly inhibited osteoblast
      differentiation markers, including alkaline phosphatase activity, nodule
      formation, osteocalcin production, and calcium deposition, without affecting cell
      proliferation or viability. These data suggest that OA is an osteoblast-related
      protein that plays an important role in the regulation of osteoblast
      differentiation and function.

PMID- 14696974
TI  - The anabolic effects of vitamin D-binding protein-macrophage activating factor
      (DBP-MAF) and a novel small peptide on bone.
AB  - Vitamin D-binding protein-macrophage activating factor (DBP-MAF) has previously
      been shown to stimulate bone resorption and correct the skeletal defects
      associated with osteopetrosis in two nonallelic mutations in rats. This same
      protein and a small fragment of the protein have now been shown to demonstrate an
      anabolic effect on the skeleton of both newborn and young adult, intact rats. The
      novel peptide fragment was synthetically produced based on the human amino acid
      sequence at the site of glycosylation in the third domain of the native protein
      (DBP). The peptide tested is 14 amino acids in length and demonstrates no
      homologies other than to that region of DBP. Newborn rats were injected i.p. with
      saline, peptide (0.4 ng/g body wt.) or DBP-MAF (2 ng/g body wt.) every other day
      from birth to 14 days of age. On day 16 the rats were euthanized and the long
      bones collected for bone densitometry by pQCT. After 2 weeks of treatment with
      either the whole protein (DBP-MAF) or the small peptide, bone density was
      significantly increased in the treated animals compared to the saline controls.
      Young adult female rats (180 grams) were given s.c. injections of saline or
      peptide (0.4 ng/g body wt. or 5 ng/g body wt.) every other day for 2 weeks; 2
      days after the final injections, the rats were euthanized and the femurs and
      tibias collected for bone densitometry. Both doses of the peptide resulted in
      significant increases in bone density as determined by pQCT. Young adult rats
      were injected locally with a single dose of the peptide (1 microg) or saline into
      the marrow cavity of the distal femur. One week after the single injection, the
      bones were collected for radiographic and histological evaluation. The saline
      controls showed no evidence of new bone formation, whereas the peptide-treated
      animals demonstrated osteoinduction in the marrow cavity and osteogenesis of
      surrounding cortical and metaphyseal bone. These data suggest that DBP-MAF and
      the synthetic peptide represent therapeutic opportunities for the treatment of a
      number of bone diseases and skeletal disorders. Systemic administration could be
      used to treat osteoporosis and a number of other osteopenias, and local
      administration could be effective in fractures, bony defect repairs, spinal
      surgery, and joint replacement.

PMID- 14696975
TI  - Ultrastructure changes induced by dry film formation of a trisodium phosphate
      blend, antimicrobial solution.
AB  - Trisodium phosphate (TSP) has been reported to have antimicrobial activity and is
      approved by the U.S. Department of Agriculture for use in food processing
      applications. A novel (U.S. Patent 6,184,198), antimicrobial solution containing
      a blend of TSP, sodium bicarbonate, and sodium carbonate (TSP blend) has
      demonstrated effective inhibition of microbial contamination in a broad spectrum
      of applications. This high-resolution cold field emission scanning electron
      microcopy (LVSEM) investigation details structural changes and dry film formation
      in various classes of microbes as a mechanism for antimicrobial activity of this
      solution. The results showed that this TSP blend solution completely inhibited
      the growth of pathogenic E. coli O157:H7, and Salmonella bacteria, the mold
      Cryptococcus, as well as a Norwalk virus surrogate-feline calicivirus. Results by
      LVSEM confirmed that the antimicrobial effect was induced when encapsulating the
      target microbes in a high lubricity film that is formed around these organisms as
      the solution dries. The thickness of the film was estimated to be approximately
      60 nm.

PMID- 14696978
TI  - A microcantilever-based pathogen detector.
AB  - The ability to detect small amounts of materials, especially bacterial organisms,
      is important for medical diagnostics and national security issues. Engineered
      micromechanical systems provide one approach for constructing multifunctional,
      highly sensitive, real-time, immunospecific biological detectors. We present
      qualitative detection of specific Salmonella enterica strains using a
      functionalized silicon nitride microcantilever. Detection is achieved due to a
      change in the surface stress on the cantilever surface in situ upon binding of a
      small number of bacteria. Scanning electron micrographs indicate that less than
      25 adsorbed bacteria are required for detection.

PMID- 14696981
TI  - Brush-like fibers on the human chromosome periphery.
AB  - A brush-like border apparently composed of fibers protruding from metaphase
      chromosomes of human lymphocytes was observed for the first time using
      transmission (TEM) and scanning electron microscopy (SEM). On the basis of size
      and sensitivity to colcemid, the fibers may be related to microtubules and
      spindle organization. The brush-like fibers were observed when chemically fixed
      metaphase chromosome spreads were placed on glass slides and maintained under
      "wet" conditions (not allowed to air dry after fixation for conventional
      cytogenetic protocols) until postfixation protocols for TEM and SEM were
      performed. The purpose of this study was to establish the occurrence of the brush
      like fibers and to determine the effects of colcemid on these fibers.

PMID- 14696983
TI  - Completion of the consonant inventory of Arabic.
AB  - This study is a follow-up of previous research on the acquisition of Arabic
      consonants in normally developing children between the ages of 2 and 6 years. The
      purpose of this study was to provide normative data on the acquisition of late
      consonants that had not been acquired by the age of 6;4 (years;months). Speech
      samples from 60 Arabic-speaking children between ages 6;6 and 8;4, in Amman,
      Jordan, were analyzed to determine the age at which 10 late consonants had been
      acquired and to determine the error patterns and sound changes used. Five of
      these consonants had still not been acquired in their standard form (Educated
      Spoken Arabic) by even the oldest children. However, 8 of the late consonants
      were produced in their acceptable colloquial forms by age 7;4 and all 10 by age
      8;4. The late acquisition of these consonants was discussed from the point of
      view of functional load and markedness. Implications for diagnosis of
      articulation disorders and reading problems were considered.

PMID- 14696984
TI  - Specific language impairment in families: evidence for co-occurrence with reading
      impairments.
AB  - Two family aggregation studies report the occurrence and co-occurrence of oral
      language impairments (LIs) and reading impairments (RIs). Study 1 examined the
      occurrence (rate) of LI and RI in children with specific language impairment (SLI
      probands), a matched control group, and all nuclear family members. Study 2
      included a larger sample of SLI probands, as well as their nuclear and extended
      family members. Probands and their family members who met specific criteria were
      classified as language and/or reading impaired based on current testing. In Study
      1, the rates of LI and RI for nuclear family members (excluding probands) were
      significantly higher than those for control family members. In the SLI families,
      affected family members were more likely to have both LI and RI than either
      impairment alone. In Study 2, 68% of the SLI probands also met the diagnostic
      classification for RI. The language and RI rates for the other family members,
      excluding probands, were 25% and 23% respectively, with a high degree of co
      occurrence of LI and RI (46%) in affected individuals. Significant sex ratio
      differences were found across generations in the families of SLI probands. There
      were more male than female offspring in these families, and more males than
      females were found to have both LIs and RIs. Results demonstrate that when LIs
      occur within families of SLI probands, these impairments generally co-occur with
      RIs. Our data are also consistent with prior findings that males show impairments
      more often than females.

PMID- 14696985
TI  - Outcomes of early language delay: I. Predicting persistent and transient language
      difficulties at 3 and 4 years.
AB  - Parent-based assessments of vocabulary, grammar, nonverbal ability, and use of
      language to refer to post and future (displaced reference) were obtained for
      8,386 twin children at 2 years of age. Children with 2 year vocabulary scores
      below the 10th centile were designated the early language delay (ELD) group, and
      their outcomes at 3 and 4 years were contrasted with the remainder of the sample,
      the typical language (TL) group. At 3 and 4 years old, children were designated
      as language impaired if their scores fell below the 15th centile on at least 2 of
      the 3 parent-provided language measures: vocabulary, grammar, and use of abstract
      language. At 3 years, 44.1% of the ELD group (as compared to 7.2% of the TL
      group) met criteria for persistent language difficulties, decreasing slightly to
      40.2% at 4 years (as compared to 8.5% of the TL group), consistent with previous
      reports of frequent spontaneous resolution of delayed language in preschoolers.
      Although relations between language and nonverbal abilities at 2 years and
      outcome at 3 and 4 years within the ELD group were highly statistically
      significant, effect sizes were small, and classification of outcome on the basis
      of data on 2-year-olds was far too inaccurate to be clinically useful. Children
      whose language difficulties persisted were not necessarily those with the most
      severe initial difficulties. Furthermore, measures of parental education and the
      child's history of ear infections failed to substantially improve the prediction.

PMID- 14696986
TI  - Outcomes of early language delay: II. Etiology of transient and persistent
      language difficulties.
AB  - Genes are known to play an important role in causing specific language
      impairment, but it is unclear how far a similar etiology is implicated in
      transient language delay in early childhood. Two-year-old children with
      vocabulary scores below the 10th centile were selected from a cohort of over
      2,800 same-sex twin pairs whose language was assessed by parental report at 2, 3,
      and 4 years of age. These children with early language delay (ELD) were divided
      into cases of transient and persistent language difficulties on the basis of
      outcome at 3 and 4 years. A DeFries-Fulker analysis (J. C. DeFries & D. W.
      Fulker, 1985) was used to compute group heritability (h2g) of 2-year vocabulary
      delay separately for those with transient and persistent difficulties. When 3
      year and 4-year language attainments were used to categorize outcomes, h2g was
      similar and modest (.25 or less) for both transient and persistent difficulties.
      However, when persistent difficulties were defined according to whether parents
      expressed concern about language at 3 years or according to whether a
      professional had been consulted about language difficulties at 4 years,
      heritability was significantly higher. For 289 children with no professional
      involvement at 4 years, heritability of 2-year vocabulary delay was close to
      zero, whereas for 134 children with professional involvement, a significant h2g
      of .41 (SE = .127) was found. Early language delay appears largely environmental
      in origin for 2-year-olds whose parents do not go on to seek professional help.

PMID- 14696987
TI  - The performance of low-income, African American children on the Preschool
      Language Scale-3.
AB  - This study examined the performance of 701 low-income African American
      preschoolers (36 to 52 months old) on the Preschool Language Scale-3 (PLS-3, I.
      L. Zimmerman, V. G. Steiner, & R. E. Pond, 1992). On average, African American
      children performed about 1 SD below the expected means for their ages on both the
      Expressive Communication and Auditory Comprehension subscales. Independent sample
      t tests showed no significant differences between African American children and a
      comparison sample of 50 European American children. Item analysis was used to
      examine the potentially problematic items of the PLS-3 for each age cohort of
      children. We found that 6 items appeared to be particularly difficult for the
      African American sample. The findings suggest that the PLS-3 is generally an
      informative language test for African American preschoolers; however, scores
      should be interpreted with caution.

PMID- 14696988
TI  - The role of syntactic complexity in treatment of sentence deficits in agrammatic
      aphasia: the complexity account of treatment efficacy (CATE).
AB  - This experiment examined the hypothesis that training production of syntactically
      complex sentences results in generalization to less complex sentences that have
      processes in common with treated structures. Using a single subject experimental
      design, 4 individuals with agrammatic aphasia were trained to comprehend and
      produce filler-gap sentences with wh-movement, including, from least to most
      complex, object-extracted who-questions, object clefts, and sentences with object
      relative clausal embedding. Two participants received treatment first on the
      least complex structure (who-questions), and 2 received treatment first on the
      most complex form (object-relative constructions), while untrained sentences and
      narrative language samples were tested for generalization. When generalization
      did not occur across structures, each was successively entered into treatment.
      Results showed no generalization across sentence types when who-questions were
      trained; however, as predicted, object-relative training resulted in robust
      generalization to both object clefts and who-questions. These findings support
      those derived from previous work, indicating not only that generalization occurs
      across structures that are linguistically related, but also that generalization
      is enhanced when the direction of treatment is from more complex to less complex
      constructions. This latter finding supports the authors' newly coined "complexity
      account of treatment efficacy" (CATE).

PMID- 14696989
TI  - The role of semantic complexity in treatment of naming deficits: training
      semantic categories in fluent aphasia by controlling exemplar typicality.
AB  - The effect of typicality of category exemplars on naming was investigated using a
      single subject experimental design across participants and behaviors in 4
      patients with fluent aphasia. Participants received a semantic feature treatment
      to improve naming of either typical or atypical items within semantic categories,
      while generalization was tested to untrained items of the category. The order of
      typicality and category trained was counterbalanced across participants. Results
      indicated that patients trained on naming of atypical exemplars demonstrated
      generalization to naming of intermediate and typical items. However, patients
      trained on typical items demonstrated no generalized naming effect to
      intermediate or atypical examples. Furthermore, analysis of errors indicated an
      evolution of errors throughout training, from those with no apparent relationship
      to the target to primarily semantic and phonemic paraphasias. Performance on
      standardized language tests also showed changes as a function of treatment.
      Theoretical and clinical implications regarding the impact of considering
      semantic complexity on rehabilitation of naming deficits in aphasia are
      discussed.

PMID- 14696990
TI  - Phonological features of child African American English.
AB  - The production of phonological features of African American English (AAE) was
      examined for 64 typically developing African American children in the 2nd through
      the 5th grade. Students read aloud passages written in Standard American English.
      Sixty of the students read the passages using AAE, and 8 different phonological
      features were represented in their readings. Phonological features were more
      frequent than morphosyntactic features. The findings as a whole support use of
      the taxonomy developed for this investigation in characterizing the phonological
      features of child AAE.

PMID- 14696991
TI  - Labeling of /s/ and [see text] by listeners with normal and impaired hearing,
      revisited.
AB  - The two aims of this study were (a) to determine the perceptual weight given
      formant transition and relative amplitude information for labeling fricative
      place of articulation perception and (b) to determine the extent of integration
      of relative amplitude and formant transition cues. Seven listeners with normal
      hearing and 7 listeners with sensorineural hearing loss participated. The
      listeners were asked to label the fricatives of synthetic consonant-vowel stimuli
      as either /s/ or [see text]. Across the stimuli, 3 cues were varied: (a) The
      amplitude of the spectral peak in the 2500-Hz range of the frication relative to
      the adjacent vowel peak amplitude in the same frequency region, (b) the frication
      duration, which was either 50 or 140 ms, and (c) the second formant transition
      onset frequency, which was varied from 1200 to 1800 Hz. An analysis of variance
      model was used to determine weightings for the relative amplitude and transition
      cues for the different frication duration conditions. A 30-ms gap of silence was
      inserted between the frication and vocalic portions of the stimuli, with the
      intent that a temporal separation of frication and transition information might
      affect how the cues were integrated. The weighting given transition or relative
      amplitude differed between the listening groups and depended on frication
      duration. Use of the transition cue was most affected by insertion of the silent
      gap. Listeners with hearing loss had smaller interaction terms for the cues than
      listeners with normal hearing, suggesting less integration of cues.

PMID- 14696992
TI  - Spectral characteristics of speech at the ear: implications for amplification in
      children.
AB  - This study examined the long- and short-term spectral characteristics of speech
      simultaneously recorded at the ear and at a reference microphone position (30 cm
      at 0 degrees azimuth). Twenty adults and 26 children (2-4 years of age) with
      normal hearing were asked to produce 9 short sentences in a quiet environment.
      Long-term average speech spectra (LTASS) were calculated for the concatenated
      sentences, and short-term spectra were calculated for selected phonemes within
      the sentences (/m/, /n/, /s/, [see text], /f/, /a/, /u/, and /i/). Relative to
      the reference microphone position, the LTASS at the ear showed higher amplitudes
      for frequencies below 1 kHz and lower amplitudes for frequencies above 2 kHz for
      both groups. At both microphone positions, the short-term spectra of the
      children's phonemes revealed reduced amplitudes for /s/ and [see text] and for
      vowel energy above 2 kHz relative to the adults' phonemes. The results of this
      study suggest that, for listeners with hearing loss (a) the talker's own voice
      through a hearing instrument would contain lower overall energy at frequencies
      above 2 kHz relative to speech originating in front of the talker, (b) a child's
      own speech would contain even lower energy above 2 kHz because of adult-child
      differences in overall amplitude, and (c) frequency regions important to normal
      speech development (e.g., high-frequency energy in the phonemes /s/ and [see
      text]) may not be amplified sufficiently by many hearing instruments.

PMID- 14696993
TI  - The effect of short-term auditory deprivation on the control of intraoral
      pressure in pediatric cochlear implant users.
AB  - The purpose of this study was to determine whether 2 speech measures (peak
      intraoral air pressure [IOP] and IOP duration) obtained during the production of
      intervocalic stops would be altered as a function of the presence or absence of
      auditory stimulation provided by a cochlear implant (CI). Five pediatric CI users
      were required to produce repetitions of the words puppy and baby with their CIs
      turned on. The CIs were then turned off for 1 hr, at which time the speech sample
      was repeated with the CI still turned off. Seven children with normal hearing
      formed a comparison group. They were also tested twice, with a 1-hr intermediate
      interval. IOP and IOP duration were measured for the medial consonant in both
      auditory conditions. The results show that auditory condition affected peak IOP
      more so than IOP duration. Peak IOP was greater for /p/ than /b/ with the CI off,
      but some participants reduced or reversed this contrast when the CI was on. The
      findings suggest that different speakers with CIs may use different speech
      production strategies as they learn to use the auditory signal for speech.

PMID- 14696994
TI  - Three treatments for teachers with voice disorders: a randomized clinical trial.
AB  - Voice problems are a common occupational hazard of teaching school, yet few
      studies exist that have objectively evaluated treatment approaches aimed at
      rehabilitating these occupation-related voice disorders. This randomized clinical
      trial used patient-based treatment outcome measures to evaluate the effectiveness
      of three treatment programs. Sixty-four teachers with voice disorders were
      randomly assigned to 1 of 3 treatment groups: voice amplification using the
      ChatterVox portable amplifier (VA; n = 25), resonance therapy (RT; n = 19), and
      respiratory muscle training (RMT; n = 20). Before and after a 6-week treatment
      phase, all teachers completed (a) the Voice Handicap Index (VHI; B. H. Jacobson
      et al., 1997), an instrument designed to appraise the self-perceived psychosocial
      consequences of voice disorders, and (b) a voice severity self-rating scale. Both
      intention-to-treat and as-treated analyses revealed that only the VA and RT
      groups reported significant reductions in mean VHI scores and in voice severity
      self-ratings following treatment. Furthermore, results from a posttreatment
      questionnaire regarding the perceived benefits of treatment showed that compared
      to RT and RMT, teachers in the VA group reported significantly more overall voice
      improvement, greater vocal clarity, and greater ease of speaking and singing
      voice following treatment. These findings replicate previous results from an
      earlier clinical trial confirming the efficacy of VA and provide new evidence to
      support RT as an effective treatment alternative for voice problems in teachers.
      The results are discussed in the context of uneven levels of self-reported
      compliance and disparate dropout rates among the treatment groups.

PMID- 14696995
TI  - Changes in the human vocal tract due to aging and the acoustic correlates of
      speech production: a pilot study.
AB  - This investigation used a derivation of acoustic reflection (AR) technology to
      make cross-sectional measurements of changes due to aging in the oral and
      pharyngeal lumina of male and female speakers. The purpose of the study was to
      establish preliminary normative data for such changes and to obtain acoustic
      measurements of changes due to aging in the formant frequencies of selected
      spoken vowels and their long-term average spectra (LTAS) analysis. Thirty-eight
      young men and women and 38 elderly men and women were involved in the study. The
      oral and pharyngeal lumina of the participants were measured with AR technology,
      and their formant frequencies were analyzed using the Kay Elemetrics Computerized
      Speech Lab. The findings have delineated specific and similar patterns of aging
      changes in human vocal tract configurations in speakers of both genders. Namely,
      the oral cavity length and volume of elderly speakers increased significantly
      compared to their young cohorts. The total vocal tract volume of elderly speakers
      also showed a significant increment, whereas the total vocal tract length of
      elderly speakers did not differ significantly from their young cohorts. Elderly
      speakers of both genders also showed similar patterns of acoustic changes of
      speech production, that is, consistent lowering of formant frequencies
      (especially F1) across selected vowel productions. Although new research models
      are still needed to succinctly account for the speech acoustic changes of the
      elderly, especially for their specific patterns of human vocal tract dimensional
      changes, this study has innovatively applied the noninvasive and cost-effective
      AR technology to monitor age-related human oral and pharyngeal lumina changes
      that have direct consequences for speech production.

PMID- 14696996
TI  - The effect of pacing strategies on the variability of speech movement sequences
      in dysarthria.
AB  - There are many potential sources of variability in speech production,
      particularly in individuals with dysarthria. The degree and time course of
      stabilization of the speech production system during recovery from a neurological
      insult is not constant across individuals. Another source of variability in
      speech production is speaking rate. Although individuals with no neurological
      impairments typically show increased variability at reduced speaking rates, this
      phenomenon has not been explored extensively in individuals with dysarthria.
      Because rate control strategies are commonly used in dysarthria treatment, it is
      of clinical importance to know if individuals with dysarthria produce less
      variable speech with rate reduction. Six individuals with mild dysarthria, 6 with
      moderate-to-severe dysarthria, and 6 matched normal controls repeated an
      utterance in four speaking rate conditions: habitual, fast, breaks between words,
      and stretched. Data were analyzed using the spatiotemporal index (STI), a
      composite measure of spatial and temporal variability across token repetitions.
      The normal controls consistently demonstrated the least variability, regardless
      of rate condition. Both groups with dysarthria were the least variable in the
      stretched condition and the most variable in the fast condition. The STI values
      of the group with moderate-to-severe dysarthria were significantly different from
      both the individuals with mild dysarthria and the normal controls. There were no
      significant differences between the group with mild dysarthria and the normal
      controls. In general, slowing the speaking rate in individuals with dysarthria
      reduces spatiotemporal variability; however, the effect of reduced spatiotemporal
      variability on intelligibility requires further investigation.

PMID- 14696997
TI  - Generalizability Theory I: Assessing reliability of observational data in the
      communication sciences.
AB  - Perceptual rating scales can be valid, reliable, and convenient tools for
      evaluating speech outcomes in research and clinical practice. However, they
      depend on the perceptions of observers. Too few raters may compromise accuracy,
      whereas too many would be inefficient. There is therefore a need to determine the
      minimum number of raters required for a reliable result. In this context, the
      ideas of Generalizability Theory have become increasingly popular in the
      behavioral sciences; suggestions have been made for their application to the
      assessment of speech-language disorders. Here we review the concepts involved,
      which are applied in a companion article dealing with speech naturalness data
      obtained from clients who recently completed treatment for their stuttering. We
      pay particular attention to the statistical requirements of the theory, including
      some cautions about possible inappropriate use of these techniques. We also offer
      a new interpretation of the results of the analysis that aims to be more
      meaningful to most speech-language pathologists.

PMID- 14696998
TI  - Generalizability Theory II: Application to perceptual scaling of speech
      naturalness in adults who stutter.
AB  - Generalizability theory has been recommended as the most comprehensive method for
      assessing the reliability of observational data. It provides a framework for
      calculating the various sources of measurement error and allows further design of
      measurements for a particular purpose. This paper gives a practical illustration
      of how this method may be used in the analysis of observational data. We use the
      ratings of 15 unsophisticated raters using the 9-point speech naturalness scale
      of R. R. Martin, S. K. Haroldson, and K. A. Triden (1984) to evaluate the speech
      of adults before and after treatment for stuttering. We calculate various sources
      of measurement error and use these to estimate the minimum number of raters and
      ratings per rater for a reliable result. For posttreatment data, the average of
      three independent raters, and for pretreatment data, the average of five
      independent raters should give a result within one scale point of the
      hypothetical true score for the speaker in at least 80% of samples. The example
      illustrates the advantages of using this method of analysis.

PMID- 14696999
TI  - Articulation rate and speech-sound normalization failure.
AB  - Not all children with speech delay (SD) of unknown origin develop fully normal
      speech even with intervention. Many retain residual distortion errors into
      adolescence and ultimately into adulthood. The current study examined whether
      articulation rate distinguishes those children who retain residual errors from
      those who normalize. Two groups of speech-delayed children originally identified
      at preschool age were retested at age 9 years (the early follow-up group) and at
      age 12-16 years (the late follow-up group), respectively. No differences in
      articulation rate were observed at either test time in conversational speech
      between those children who continued to produce residual distortion errors (RE)
      compared to those children who had fully normalized speech (NSA). For the late
      follow-up group, children in the RE outcome group articulated speech at
      significantly slower rates than the children in the NSA outcome group in an
      embedded words task using both syllables per second and phones per second
      measures. Findings suggested that children with SD of unknown origin who fail to
      normalize may have relative speech-motor deficits and possibly deficits in
      language formulation skill. Alternatively, slower articulation rate in structured
      tasks may represent some sort of compensation for the continuing presence of
      speech-sound errors. Possible motivations for such compensation are discussed.

PMID- 14697000
TI  - Vowel category dependence of the relationship between palate height, tongue
      height, and oral area.
AB  - This article evaluates intertalker variance of oral area, logarithm of the oral
      area, tongue height, and formant frequencies as a function of vowel category. The
      data consist of coronal magnetic resonance imaging (MRI) sequences and acoustic
      recordings of 5 talkers, each producing 11 different vowels. Tongue height (left,
      right, and midsagittal), palate height, and oral area were measured in 3 coronal
      sections anterior to the oropharyngeal bend and were subjected to multivariate
      analysis of variance, variance ratio analysis, and regression analysis. The
      primary finding of this article is that oral area (between palate and tongue)
      showed less intertalker variance during production of vowels with an oral place
      of articulation (palatal and velar vowels) than during production of vowels with
      a uvular or pharyngeal place of articulation. Although oral area variance is
      place dependent, percentage variance (log area variance) is not place dependent.
      Midsagittal tongue height in the molar region was positively correlated with
      palate height during production of palatal vowels, but not during production of
      nonpalatal vowels. Taken together, these results suggest that small oral areas
      are characterized by relatively talker-independent vowel targets and that meeting
      these talker-independent targets is important enough that each talker adjusts his
      or her own tongue height to compensate for talker-dependent differences in
      constriction anatomy. Computer simulation results are presented to demonstrate
      that these results may be explained by an acoustic control strategy: When talkers
      with very different anatomical characteristics try to match talker-independent
      formant targets, the resulting area variances are minimized near the primary
      vocal tract constriction.

PMID- 14697001
TI  - Exchange of disfluency with age from function words to content words in spanish
      speakers who stutter.
AB  - The main purpose of the present study was to examine whether the developmental
      change in loci of disfluency from mainly function words to mainly content words,
      observed for English speakers who stutter (P. Howell, J. Au-Yeung, & S. Sackin,
      1999), also occurs for comparable Spanish speakers who stutter. The participants
      were divided into 5 age groups. There were 7 participants in Group 1, from 3 to 5
      years old; 11 in Group 2, from 6 to 9 years old; 10 in Group 3, from 10 to 11
      years old; 9 in Group 4, from 12 to 16 years old; and 9 in Group 5, from 20 to 68
      years old. Across all groups, 36 of the 46 participants were male. The study
      method involved segmenting speech into phonological words (PWs) that consist of
      an obligatory content word with optional function words that precede and follow
      it. The initial function words in the PWs were examined to establish whether they
      have a higher disfluency rate than the final ones (J. Au-Yeung, P. Howell, & L.
      Pilgrim, 1998). Disfluency on function words in a PW was higher when the word
      occurred before a content word rather than after a content word for all age
      groups. Disfluencies on function and content words were then examined to
      determine whether they change over age groups in the same way as for English
      speakers who stutter (Howell et al., 1999). The rate of disfluency on function
      words was higher than that on content words, particularly in the youngest
      speakers. Function word disfluency rate dropped off and content word disfluency
      rate increased across age groups. These patterns are similar to those reported
      for English. Possible explanations for these similarities across the two
      languages are discussed.

PMID- 14697002
TI  - Automatic brain tumor segmentation by subject specific modification of atlas
      priors.
AB  - RATIONALE AND OBJECTIVES: Manual segmentation of brain tumors from magnetic
      resonance images is a challenging and time-consuming task. An automated system
      has been developed for brain tumor segmentation that will provide objective,
      reproducible segmentations that are close to the manual results. Additionally,
      the method segments white matter, grey matter, cerebrospinal fluid, and edema.
      The segmentation of pathology and healthy structures is crucial for surgical
      planning and intervention. MATERIALS AND METHODS: The method performs the
      segmentation of a registered set of magnetic resonance images using an
      expectation-maximization scheme. The segmentation is guided by a spatial
      probabilistic atlas that contains expert prior knowledge about brain structures.
      This atlas is modified with the subject-specific brain tumor prior that is
      computed based on contrast enhancement. RESULTS: Five cases with different types
      of tumors are selected for evaluation. The results obtained from the automatic
      segmentation program are compared with results from manual and semi-automated
      methods. The automated method yields results that have surface distances at
      roughly 1-4 mm compared with the manual results. CONCLUSION: The automated method
      can be applied to different types of tumors. Although its performance is below
      that of the semi-automated method, it has the advantage of requiring no user
      supervision.

PMID- 14697003
TI  - Myocardial delineation via registration in a polar coordinate system.
AB  - RATIONALE AND OBJECTIVES: Cardiovascular disease is the number one cause of
      premature death in the western world. Analysis of cardiac function provides
      clinically useful diagnostic and prognostic information; however, manual analysis
      of function via delineation is prohibitively time consuming. This article
      describes a technique for analysis of dynamic magnetic resonance images of the
      left ventricle using a non-rigid registration algorithm. A manually delineated
      contour of a single phase was propagated through the dynamic sequence. MATERIALS
      AND METHODS: Short-axis cine magnetic resonance images were resampled into polar
      coordinates before all the time frames were aligned using a non-rigid
      registration algorithm. The technique was tested on 10 patient data sets, a total
      of 1,052 images were analyzed. RESULTS: Results of this approach were
      investigated and compared with manual delineation at all phases in the cardiac
      cycle, and with registration performed in a Cartesian coordinate system. The
      results correlated very well with manually delineated contours. CONCLUSION: A
      novel approach to the registration and subsequent delineation of cardiac magnetic
      resonance images has been introduced. For the endocardium, the polar resampling
      technique correlated well with manual delineation, and better than for images
      registered without radial resampling in a Cartesian coordinate system. For the
      epicardium, the difference was not as apparent with both techniques correlating
      well.

PMID- 14697004
TI  - Statistical validation based on parametric receiver operating characteristic
      analysis of continuous classification data.
AB  - RATIONALE AND OBJECTIVES: The accuracy of diagnostic test and imaging
      segmentation is important in clinical practice because it has a direct impact on
      therapeutic planning. Statistical validations of classification accuracy was
      conducted based on parametric receiver operating characteristic analysis,
      illustrated on three radiologic examples, MATERIALS AND METHODS: Two parametric
      models were developed for diagnostic or imaging data. Example 1: A semi-automated
      fractional segmentation algorithm was applied to magnetic resonance imaging of
      nine cases of brain tumors. The tumor and background pixel data were assumed to
      have bi-beta distributions. Fractional segmentation was validated against an
      estimated composite pixel-wise gold standard based on multi-reader manual
      segmentations. Example 2: The predictive value of 100 cases of spiral computed
      tomography of ureteral stone sizes, distributed as bi-normal after a non-linear
      transformation, under two treatment options received. Example 3: One hundred
      eighty cases had prostate-specific antigen levels measured in a prospective
      clinical trial. Radical prostatectomy was performed in all to provide a binary
      gold standard of local and advanced cancer stages. Prostate-specific antigen
      level was transformed and modeled by bi-normal distributions. In all examples,
      areas under the receiver operating characteristic curves were computed. RESULTS.
      The areas under the receiver operating characteristic curves were: Example 1:
      Fractional segmentation of magnetic resonance imaging of brain tumors:
      meningiomas (0.924-0.984); astrocytomas (0.786-0.986); and other low-grade
      gliomas (0.896-0.983). Example 3: Ureteral stone size for treatment planning
      (0.813). Example 2: Prostate-specific antigen for staging prostate cancer
      (0.768). CONCLUSION: All clinical examples yielded fair to excellent accuracy.
      The validation metric area under the receiver operating characteristic curves may
      be generalized to evaluating the performances of several continuous classifiers
      related to imaging.

PMID- 14697005
TI  - Analysis and 3-dimensional visualization of neurovascular compression syndromes.
AB  - RATIONALE AND OBJECTIVES: Neurovascular compression syndromes are currently
      examined with 2-dimensional representations of tomographic volumes. To overcome
      this drawback, coarse segmentation followed by direct volume rendering of
      magnetic resonance (MR) data is introduced supporting a detailed 3-dimensional
      analysis of the related structures. MATERIALS AND METHODS: This approach is based
      on MR-CISS (constructive interference in steady state) volumes providing the
      required high resolution to achieve an improved spatial understanding. In
      relation to the size of the involved nerves and vessels, an explicit segmentation
      is extremely difficult. Therefore, a semi-automatic preprocessing sequence was
      developed consisting of noise reduction, morphologic filtering, and volume
      growing. To delineate the target structures within the segmented and labeled
      subvolumes, interactive direct volume rendering was applied that allows
      delineating the target structures in the area of the cerebrospinal fluid with
      implicit segmentation based on predefined transfer functions assigning opacity
      and color values to the intensity values of the image data. For a further
      improved analysis, registration of the MR-CISS volumes with MR angiography is
      recommended to support differentiating vessels and nerves on the one side and
      arteries and veins on the other. RESULTS: The presented method was applied in a
      consecutive series of 47 cases of different neurovascular compression syndromes,
      supporting the presurgical analysis of the image data. Additionally, the results
      were compared with the operative findings. CONCLUSION: Overall, this approach
      contributes significantly to an optimized 3-dimensional analysis and
      understanding of neurovascular compression syndromes. Based on the obtained
      results, it is of high value for the planning of surgery.

PMID- 14697006
TI  - A method for detecting undisplayed regions in virtual colonoscopy and its
      application to quantitative evaluation of fly-through methods.
AB  - RATIONALE AND OBJECTIVES: When virtual endoscopy is used as a diagnostic tool,
      especially as a tool for detecting colon polyps, the user often performs
      automated fly-through based on automatically generated paths. In the case of
      automated fly-through in the colon, there are some blind areas at the backs of
      folds. The aim of this study is to detect undisplayed regions during fly-through
      and to perform quantitative evaluation. MATERIALS AND METHODS: Undisplayed
      regions are detected by marking displayed triangles for surface rendering or
      displayed voxels for volume rendering. The voxels or triangles not having
      displayed marks are considered to be undisplayed triangles or voxels. Various
      kinds of automated fly-through paths generated from medial axes of the colon and
      flattened views of the colon from the viewpoint of the rate of undisplayed
      regions are evaluated. RESULTS: The experiment results show that about 30% of
      colon regions are classified as undisplayed regions by the conventional automated
      fly-through along the medial axis and that the flattened view results in very few
      undisplayed regions. CONCLUSION: There is a possibility that the automated fly
      through methods may cause many undisplayed regions.

PMID- 14697007
TI  - Alzheimer's disease and frontotemporal dementia exhibit distinct atrophy-behavior
      correlates: a computer-assisted imaging study.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to test the hypothesis
      that distinct patterns of gray matter atrophy are responsible for unique
      interruptions of the naming process in Alzheimer's disease (AD) and
      frontotemporal dementia (FTD). MATERIALS AND METHODS: Voxel-based morphometry
      (VBM) was performed to characterize at the voxel level the neuroanatomic changes
      that occur in AD and FTD based on high-resolution T1-weighted three-dimensional
      (3D) spoiled-gradient echo images of patients (AD, n = 12; FTD, n = 29) and
      healthy control subjects (n = 12). The cortical atrophy measurements were
      correlated with performance on behavioral measures of naming and related
      processes to identify brain regions that may contribute to this language
      function. RESULTS: Both AD and FTD have significant naming difficulty, and this
      difficulty in naming correlates with a measure of lexical retrieval in both
      patient groups as well. However, only FTD patients showed a correlation with
      semantic memory. Areas of cortical atrophy common to AD and FTD were found in the
      anterior temporal, posterolateral temporal, and dorsolateral prefrontal regions
      of the left hemisphere. Correlation with naming in both AD and FTD was seen in
      the left anterior temporal cortex, suggesting that this area may play a role in
      the lexical retrieval component of naming. We also observed several unique areas
      of cortical atrophy in temporal and frontal cortices of these patients. Right
      anterior temporal and left posterolateral temporal regions of atrophy correlated
      with naming difficulty in FTD, suggesting that these areas may contribute to the
      semantic memory component of naming. Cortical areas correlating with naming that
      are not atrophic may represent regions that play an optional role in naming.
      CONCLUSION: VBM provides an important first step in analyzing brain-behavior
      relations in vivo in patients with neurodegenerative diseases. More refined
      analyses of brain morphology via high-dimensional normalization methods that are
      capable of modeling local as well as global variability in neuroanatomical
      structure promise to be even more informative.

PMID- 14697008
TI  - Example-based assisting approach for pulmonary nodule classification in three
      dimensional thoracic computed tomography images.
AB  - RATIONALE AND OBJECTIVES: An example-based assisting approach that supports
      decision making in classifying pulmonary nodules in 3-dimensional (3D) thoracic
      computed tomography images has been developed. MATERIALS AND METHODS: The example
      based assisting approach retrieves and displays nodules that exhibit morphologic
      and internal profiles consistent to the nodule in question. It uses a 3D computed
      tomography image database containing 143 pulmonary nodules for which diagnosis is
      known. The central module makes possible analysis of the query nodule image and
      extraction of the features of interest: shape, surrounding structure, and
      internal structure of the nodules. The principal axes and the compactness
      characterize the nodule shape. The surrounding and internal structures are
      represented by the distribution pattern of computed tomography density value and
      3D curvature indexes. The nodule representation is then used for computing a
      similarity measure such as a correlation coefficient and a malignant likelihood
      of the query nodule. The malignant likelihood is estimated by the difference
      between the representation patterns of the query case and the retrieved lesions.
      The Mahalanobis distance was adopted as the difference measure. The approach
      performance was assessed through leave-one-out method by the false-positive rate.
      RESULTS: Given a query nodule image, the proposed method retrieved benign and
      malignant images similar to the query case and provided its malignant likelihood.
      The number of cases that obtained enough number of the retrieved cases for
      estimating the malignant likelihood was 107 cases (malignant, 70; benign, 37) in
      our database. Sensitivity was 91.4% (64 of 70 malignant nodules), specificity was
      51.4% (19 of 37 benign nodules), and accuracy values were 77.6% (83 of 107
      nodules). CONCLUSION: Preliminary assessment of this approach showed that an
      example-based assisting approach is an effective tool for making the diagnostic
      decision in the classification of pulmonary nodules using the nodule image
      database.

PMID- 14697009
TI  - Level set-based integration of segmentation and computational fluid dynamics for
      flow correction in phase contrast angiography.
AB  - RATIONALE AND OBJECTIVES: A novel method to correct flow data from magnetic
      resonance phase contrast (MR-PC) angiography, based on combining computational
      fluid dynamics and segmentation in a level set framework, was developed and
      tested in this study. MATERIALS AND METHODS: The MR-PC velocity data was used in
      a partial differential equation-based level set method for vessel segmentation.
      The results were supplied as the quantitative description of the vessel wall to
      the flow field solver using computational fluid dynamics, based on the level set
      method, to obtain a physically meaningful flow. The most significant
      characteristic of our novel approach is that it requires light computational
      loads, especially insofar as it avoids generation of complex computational grid
      system. The integration of segmentation and computational fluid dynamics in a
      level set framework is shown to be both robust and economic, and yet yields a
      physically correct velocity field and optimal vessel geometry. RESULTS: The
      application to the flow field in a straight tube with circular cross section of
      constant radius demonstrated the validity of out new approach, especially the
      treatment of the velocity boundary conditions on the solid wall. Simulation of
      the velocity field in both common carotid artery and bifurcation of basilar and
      vertebral arteries, based on clinical MR-PC data, provided with smooth and stable
      results. CONCLUSION: Applying this procedure to both synthetic and clinical data,
      significant improvement of the blood velocity field, such as a smooth velocity
      distribution aligned along the vessels and removal of burst or error vectors,
      could be observed. This procedure also offers possibilities for improved vessel
      segmentation.

PMID- 14697010
TI  - Endpoint localization in guide wire tracking during endovascular interventions.
AB  - RATIONALE AND OBJECTIVES: A method is presented to track guide wires during
      endovascular interventions under X-ray fluoroscopy. Accurate guide wire tracking
      can be used to improve guide wire visualization in the low quality fluoroscopic
      images, and to estimate the position of the guide wire in world coordinates for
      navigation purposes. MATERIALS AND METHODS: A two-step procedure is used to track
      the guide wire in subsequent frames. First, the position of the guide wire is
      obtained by fitting a spline to the image. Subsequently, the spline is
      iteratively moved toward the tip of the guide wire for accurate tip localization.
      For both steps, a feature image is used in which line-like structures are
      enhanced. The method is validated using a reference standard, obtained by manual
      tracings of three observers. RESULTS: The method is evaluated on 20 image
      sequences, 10 sequences with a J-tipped guide wire and 10 with a straight guide
      wire. The tracking success was 96% for J-tipped and 100% for straight guide
      wires, whereas accurate endpoint localization could be performed in 91.3% and
      94.4% of the frames respectively, with a tip localization error of less than 1.5
      mm. CONCLUSIONS: Accurate endpoint localization can be performed for both J
      tipped and straight guide wires and therefore the presented tracking method can
      be used for navigation purposes.

PMID- 14697011
TI  - Intra-procedural coronary intervention planning using hybrid 3-dimensional
      reconstruction techniques.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to develop a method to
      assist the cardiologist in planning an interventional procedure while the patient
      is on the catheterization table. MATERIALS AND METHODS: A rotational single plane
      x-ray system is used to acquire images while rapidly rotating the C-arm around
      the patient. Based on electrocardiogram-selected projections, both a volumetric
      cone-beam reconstruction of the coronary tree as well as a three-dimensional
      model of the vessel segment of interest is generated. This information is used to
      compute the appropriateness of a range of different viewing angles with respect
      to the overlap and foreshortening of the vessel segment of interest during the
      cardiac cycle which results in an interactive optimal view map. RESULTS: The
      proposed method has been tested on patient data and several phantom objects. The
      results show that both an accurate 3D model of a vessel segment of interest and
      its associated optimal view map can be generated to predict an appropriate gantry
      angle for subsequent image acquisition. CONCLUSION: The method provides an
      appropriate and feasible tool to assist interventional cardiologists in planning
      a coronary intervention while the patient is still on the catheterization table
      following diagnostic coronary angiography.

PMID- 14697012
TI  - Advanced computer assistance for magnetic resonance-guided microwave
      thermocoagulation of liver tumors.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to utilize computer
      assistance effectively for both easy and accurate magnetic resonance (MR) image
      guided microwave thermocoagulation therapy of liver tumors. MATERIALS AND
      METHODS: An open configuration MR scanner and a microwave coagulator at 2.45 GHz
      were used. Navigation software, a 3D Slicer, was customized to combine
      fluoroscopic MR images and preoperative MR images for the navigation. New
      functions to display MR temperature maps with simple parameter setting, and to
      record and display the coagulated areas by multiple microwave ablations in the 3
      dimensional space (footprinting), were also introduced into the software. The VGA
      signal of the computer display was directly transferred to the surgeon's monitor.
      RESULTS: The customized software could be used for both accurate image navigation
      and convenient and easy temperature monitoring. Because repeated punctures and
      ablations are usually required in this procedure, the footprinting function made
      targeting of the tumors both easy and accurate and was quite effective in
      achieving the necessary and sufficient treatment. Furthermore, clear display on
      the surgeon's monitor, which was obtained by direct transfer of the VGA signal,
      enabled precise image navigation. CONCLUSION: The newly developed computer
      assistance was quite useful and helpful for this MR-guided procedure.

PMID- 14697013
TI  - Advances in contrast media research.

PMID- 14697014
TI  - Academic radiology: the reasons to stay or leave.
AB  - RATIONALE AND OBJECTIVES: To find major reasons why junior academic radiologists
      leave academia for private practice and to suggest future changes to motivate
      them to stay. MATERIALS AND METHODS: 2000 surveys were sent to every tenth member
      of the Radiological Society of North America (RSNA) who completed training within
      the past decade. Those in academic institutions and those who left within 5 years
      were asked to respond. RESULTS: 132 radiologists responded. Thirty-two percent of
      responders were in academic radiology. Of those in academic radiology, 71% plan
      to stay at the same institution, 7% are planning to move to another academic
      institution, 17% are considering private practice, and 5% are leaving for private
      practice. The main reasons to leave were low pay and lack of academic time. Sixty
      eight percent of responders already left academia after an average of 3.28 years.
      Ninety-five percent feel the decision was good, and 65% would not go back. Forty
      nine percent experienced more than 100% pay increase, 60% feel they work harder,
      and 62% feel quality of life is better. CONCLUSION: Significant changes should be
      made to motivate junior radiologists to stay in academia. Developing leaders in
      radiology is a must, and should be a top priority. Academic radiologists should
      not be expected to read private practice volumes and still have time to produce
      quality research and teaching. Clinical duties should be limited to 32 hours per
      week. At least 1 day a week should be protected academic time. Efforts should be
      made to decrease the discrepancy between incomes. Mentoring is important,
      allowing a smooth transition for junior faculty members to optimize academic
      progress and lead to promotion.

PMID- 14697015
TI  - The good, the bad and the... or just keeping up appearances!!

PMID- 14697016
TI  - Xerostomia: clinical aspects and treatment.
AB  - Xerostomia or dry mouth is a condition that is frequently encountered in dental
      practice. The most common cause is the use of certain systemic medications, which
      make the elderly at greater risk because they are usually more medicated. Other
      causes include high doses of radiation and certain diseases such as Sjogren's
      syndrome. Xerostomia is associated with difficulties in chewing, swallowing,
      tasting or speaking. This results in poor diet, malnutrition and decreased social
      interaction. Xerostomia can cause oral discomfort, especially for denture
      wearers. Patients are at increased risk of developing dental caries. A thorough
      intraoral and extra-oral clinical examination is important for diagnosis.
      Treatment may include the use of salivary substitutes (Biotene), salivary
      stimulants such as pilocarpine, ongoing dental care, caries prevention, a review
      of the current prescription drug regimen and possible elimination of drugs having
      anticholinergic effects. Because of the ageing population, and the concomitant
      increase in medicated individuals, dentists can expect to be presented with
      xerostomia in an increasing number of patients in the coming years and therefore
      should be familiar with its diagnosis and treatment. Therefore, the purpose of
      this review is to outline for clinicians the common aetiologies, clinical
      identification, and routine therapeutic modalities available for individuals with
      xerostomia.

PMID- 14697017
TI  - Association between dental health behaviours, mental/physical function and self
      feeding ability among the elderly: a cross-sectional survey.
AB  - OBJECTIVES: The aim of this study was to determine the association between dental
      health behaviour, mental/physical function and self-feeding ability among the
      elderly. SUBJECTS: A total of 414 elderly dental patients aged 65 years and older
      participated in this study. METHODS: A survey was carried out for three years and
      seven months starting in January 1998 at the Chubu National Hospital. The
      patients or their carers were examined/interviewed about the severity of senile
      dementia, dental health behaviour, ability to rinse their mouths, ability to
      manage dentures, and ability to sit at a table during meals. To assess the
      association with self-feeding ability among the elderly, cut-offs were given for
      these variables, and then the odds ratios were calculated. RESULTS: The strongest
      association to self-feeding ability was marked by inability to rinse their own
      mouth, followed by inability to manage dentures, inability to sit at a table
      during meals, severe senile dementia and less frequency of toothbrushing.
      CONCLUSION: Elderly who have lost the feeding ability often could not maintain
      their dental health by themselves. Carers must provide not only a feeding service
      with acknowledgement of aspiration but oral care to prevent dental disease and
      fatal pneumonia in the elderly.

PMID- 14697018
TI  - High correlation between the bacterial species in denture plaque and pharyngeal
      microflora.
AB  - OBJECTIVES: The morbidity and mortality of the dependent elderly that result from
      aspiration pneumonia are recognized as a major geriatric health problem. Most
      cases of bacterial pneumonia are initiated following colonization or
      superinfection of the pharynx by pathogenic bacteria, followed by aspiration of
      pharyngeal contents. A recent study revealed that bacteria, that commonly cause
      respiratory infection, colonized the dentures of dependent elderly. This suggests
      that denture plaque may function as a reservoir of potential respiratory
      pathogens to facilitate colonization on the pharynx. The purpose of this study
      was to determine the possible correlation between denture and pharyngeal
      microflora. STUDY DESIGN: The denture and pharyngeal bacterial flora of 50
      dependent elderly were examined, and the microorganisms identified by culturing.
      The agreement between the bacterial species in denture plaque and pharyngeal
      microflora was investigated using the Kappa method. RESULTS: The microorganism
      species on the dentures and pharyngeal mucosa of the subjects had an agreement
      rate of 68.5%. The agreement rate for each of the bacterial species of the
      dentures and pharynx was also demonstrated to be high. CONCLUSIONS: Dentures
      should be considered an important reservoir of organisations which could colonise
      the pharynx, and the importance of controlling denture plaque for the prevention
      of aspiration pneumonia cannot be overemphasized.

PMID- 14697019
TI  - Continuing dental care for Highlands elderly: current practice and attitudes of
      dental practitioners and home supervisors.
AB  - OBJECTIVE: To investigate current practice and attitudes of Highland dentists and
      home supervisors to continued dental care of elderly residents. METHODS: A cross
      sectional questionnaire was designed to survey the current practice and attitudes
      of Highland dentists and residential care supervisors in their provision of
      dental care for the elderly at home and in long stay accommodation. RESULTS: The
      response rate was 94% of dentists and 79% of homes. Despite 86% of dentists
      providing domiciliary care and 93% of homes transport to a surgery, no more than
      a quarter of residents had had contact with a dentist in the previous year. The
      distribution of residents varied with dependant individuals living in nursing
      units and the least dependant in residential homes. Only 1% of all residents were
      totally bed bound. Domiciliary patients were less likely to receive continuing
      care compared with those seen in a surgery and 75% of homes had to initiate
      dental care. In terms of patient referral, the majority of GDPs would refer
      uncooperative patients, salaried dentists would refer those with complex medical
      histories and community dentists would refer those requiring complex treatments.
      A dental assessment was undertaken in 46% of homes and 81% of these kept a record
      of dental care. CONCLUSION: This study highlights the need for a co-ordinated,
      seamless continuing dental care service, tailored to the actual needs of the
      elderly individuals it is designed to serve, particularly in a remote and rural
      area.

PMID- 14697020
TI  - Validation of a Sinhalese translation of the Oral Health Impact Profile-14 for
      use with older adults.
AB  - OBJECTIVE: To test the psychometric properties of a Sinhalese translation of the
      OHIP-14 scale for use among older adults in Sri Lanka. DESIGN: A cross-sectional
      survey. The English version of the OHIP-14 was translated in to Sinhalese, pre
      tested and subsequently administered to the subjects by a trained interviewer.
      SETTING: Moratuwa--a densely populated urban area in the Western province of Sri
      Lanka. SUBJECTS: 585 individuals aged 60 years and above. MAIN OUTCOME MEASURES:
      Reliability of the translated scale was assessed in terms of internal consistency
      using Cronbach's alpha. Construct validity was evaluated by examining the
      associations between perceived oral health status, perceived need for dental care
      and the OHIP scores. RESULTS: Cronbach's alpha of the translated scale was 0.93.
      Corrected item-total correlation coefficients ranged from 0.53-0.80. The highly
      significant associations between perceived oral health status, perceived need for
      dental care and the OHIP scores support the construct validity of the translated
      scale. CONCLUSION: The Sinhalese translation of the OHIP-14 is a valid and
      reliable instrument to measure oral health related quality of life in older
      adults of Sri Lanka.

PMID- 14697021
TI  - The influence of age and denture wear on the size of edentulous structures.
AB  - OBJECTIVES: This study was designed to evaluate the influence of age and denture
      use on the size of arches and residual ridges in edentulous patients. DESIGN: At
      two nursing homes, maxillary and mandibular stone casts of 302 fully edentulous
      patients were utilized to measure the size of the arches and residual ridges,
      according to age and use of complete dentures. Age cohorts were divided into
      three groups; 60-69, 70-79, and 80-89 years old. Two hundred and forty-nine
      denture wearers used complete dentures for at least 2 years before examinations.
      Fifty-three non-denture users had never worn removable prostheses. Chi-square
      analysis (p<0.05) was used to establish the possible relations between the linear
      values and the size indexes of the ridges and arches and the two examined
      parameters: age and denture wear. RESULTS: Young old patients possessed
      edentulous structures that were not significantly larger than elderly old
      patients in both the maxilla and the mandible. Non-denture users had
      significantly bigger arches and ridges in both edentulous jaws than denture
      users. CONCLUSIONS: Young old, non-denture users tended to have bigger residual
      edentulous tissues compared to elderly old patients who used complete dentures.

PMID- 14697022
TI  - Clinical reversal of root caries using ozone, double-blind, randomised,
      controlled 18-month trial.
AB  - OBJECTIVE: To assess the effect of an ozone delivery system, combined with the
      daily use of a remineralising patient kit, on the clinical severity of non
      cavitated leathery primary root carious lesions (PRCL's), in an older population
      group. DESIGN: A total of 89 subjects, (age range 60-82, mean +/- SD, 70.8 +/- 6
      years), each with two leathery PRCL's, were recruited. The two lesions in each
      subject were randomly assigned for treatment with ozone or air, in a double-blind
      design, in a general dental practice. Subjects were recalled at three, six, 12
      and 18 months. Lesions were clinically recorded at each visit as soft, leathery
      or hard, scored with a validated root caries severity index. RESULTS: There were
      no observed adverse events. After three months, in the ozone-treated group, 61
      PRCL's (69%) had become hard and none had deteriorated, whilst in the control
      group, four PRCL's (4%) had become worse (p<0.01). At the six-month recall, in
      the ozone group, seven PRCL's (8%) remained leathery, the remaining 82 (92%)
      PRCL's had become hard, whilst in the control group, 10 PRCL's had become worse
      (11%) and one had become hard (p<0.01). At 12 and 18 months, 87 Subjects
      attended. In the ozone group at 12 months, two PRCL's remained leathery, compared
      to 85 (98%) that had hardened, whilst in the control group 21 (24%) of the PRCL's
      had progressed from leathery to soft, i.e. became worse, 65 PRCL's (75%) were
      still leathery, and one remained hard (p<0.01). At 18 months, 87 (100%) of ozone
      treated PRCL's had arrested, whilst in the control group, 32 lesions (37%) of the
      PRCL's had worsened from leathery to soft (p<0.01), 54 (62%) PRCL's remained
      leathery and only one of the control PRCL's had reversed (p<0.01). CONCLUSIONS:
      Leathery non-cavitated primary root caries can be arrested non-operatively with
      ozone and remineralising products. This treatment regime is an effective
      alternative to conventional "drilling and filling".

PMID- 14697023
TI  - The importance of outcome measurement in evidence-based medicine.

PMID- 14697024
TI  - Satellite meeting in Gothenburg held by the European College of Gerodontology
      (ECG), the Prosthodontic Research Group (PRG) and Geriatric Oral Research Group
      (GORG) of the IADR.

PMID- 14697025
TI  - Quantitative submonolayer spatial mapping of Arg-Gly-Asp-containing peptide
      organomercaptan gradients on gold with matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - Peptides containing the tripeptide sequence Arg-Gly-Asp (RGD) have the ability to
      bind to members of the integrin superfamily of cell-surface receptors and direct
      cellular adhesion and haptotaxis. The goal of this work is the development of a
      rapid and effective method for the quantitative submonolayer spatial composition
      mapping of surfaces displaying molecular assemblies of RGD-containing
      organomercaptan peptides on a Au surface using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-MS). Quantitation
      of the RGD peptide is achieved by determining the peak intensity of the
      protonated molecular ion, (M + H)+, relative to the (M + H)+ peak for an internal
      standard, which is similar chemically but with glutamic acid (E) substituted for
      aspartic acid (D). Using optimized sample preparation procedures, a bilinear
      calibration was obtained between the quantitative peak intensity ratio and the
      mole fraction of the RGD-containing peptide. Quantitative compositions were
      determined with relative standard deviations of <10%, even in the presence of 10x
      spot-to-spot variations in the absolute signal intensities, by using this
      internal standard approach. This MALDI-MS quantitative analysis method was
      employed to probe variable-width two-component counterpropagating
      electrochemically generated gradients of the two peptides, prepared by coupling
      in-plane electrochemical potential gradients with the electrosorption reactions
      of organothiols to vary the composition laterally. The measured lateral
      composition profiles match the quasi-linear potential gradient model and yield
      profiles that overlap to a high degree of fidelity in potential space. Thus,
      MALDI-MS spatial composition mapping should become a powerful tool for the
      preparation of designed surfaces facilitating the study of cellular adhesion and
      motility and cell-cell interactions.

PMID- 14697026
TI  - Real-time nucleic acid sequence-based amplification in nanoliter volumes.
AB  - Real-time nucleic acid sequence-based amplification (NASBA) is an isothermal
      method specifically designed for amplification of RNA. Fluorescent molecular
      beacon probes enable real-time monitoring of the amplification process.
      Successful identification, utilizing the real-time NASBA technology, was
      performed on a microchip with oligonucleotides at a concentration of 1.0 and 0.1
      microM, in 10- and 50-nL reaction chambers, respectively. The microchip was
      developed in a silicon-glass structure. An instrument providing thermal control
      and an optical detection system was built for amplification readout. Experimental
      results demonstrate distinct amplification processes. Miniaturized real-time
      NASBA in microchips makes high-throughput diagnostics of bacteria, viruses, and
      cancer markers possible, at reduced cost and without contamination.

PMID- 14697027
TI  - Separation of long DNA molecules by quartz nanopillar chips under a direct
      current electric field.
AB  - We have established the nanofabrication technique for constructing nanopillars
      with high aspect ratio (100-500 nm diameter and 500-5000 nm tall) inside a
      microchannel on a quartz chip. The size of pillars and the spacing between
      pillars are designed as a DNA sieving matrix for optimal analysis of large DNA
      fragments over a few kilobase pairs (kbp). A chip with nanopillar channel and
      simple cross injector was developed based on the optimal design and applied to
      the separation of DNA fragments (1-38 kbp) and large DNA fragments (lambda DNA,
      48.5 kbp; T4 DNA, 165.6 kbp) that are difficult to separate on conventional gel
      electrophoresis and capillary electrophoresis without a pulsed-field technique.
      DNA fragments ranging from 1 to 38 kbp were separated as clear bands, and
      furthermore, the mixture of lambda DNA and T4 DNA was successfully separated by a
      380-microm-long nanopillar channel within only 10 s even under a direct current
      (dc) electric field. Theoretical plate number N of the channel (380-1450 microm
      long) was 1000-3000 (0.7 x 10(6)-2.1 x 10(6) plates/m). A single DNA molecule
      observation during electrophoresis in a nanopillar channel revealed that the
      optimal nanopillars induced T4 DNA to form a narrow U-shaped conformation during
      electrophoresis whereas lambda DNA kept a rather spherical conformation. We
      demonstrated that, even under a dc electric field, the optimal nanopillar
      dimensions depend on a gyration radius of DNA molecule that made it possible to
      separate large DNA fragments in a short time.

PMID- 14697028
TI  - Open tubular capillary electrochromatography of synthetic peptides on etched
      chemically modified columns.
AB  - Two sets of peptides, each having structurally similar amino acid sequences, have
      been investigated by capillary electrochromatography (CEC) using etched
      chemically modified capillaries as the separation medium. In comparison to
      gradient RP-HPLC, the resolving power of the described CEC methods has been found
      to be superior. A number of variables have been examined with respect to
      optimization of the separation of these closely related peptides with several
      different etched chemically modified capillaries. These experimental variables
      included the nature of the bonded moiety, the pH, the organic modifier type, and
      the amount of organic modifier in the buffer electrolyte. Systematic variation of
      these parameters results in significant changes in the migrational behavior of
      the investigated peptides and provides important insight into the underlying
      molecular separation processes that prevail in open tubular CEC. Moreover, under
      optimized conditions, efficient separations characterized by highly symmetrical
      peaks were achieved. In addition, this study has permitted the long-term
      stability as well as the short-term and long-term reproducibility of the etched
      chemically modified capillaries to be documented.

PMID- 14697030
TI  - Discrimination of bacteria using surface-enhanced Raman spectroscopy.
AB  - Raman spectroscopy has recently been shown to be a potentially powerful whole
      organism fingerprinting technique and is attracting interest within microbial
      systematics for the rapid identification of bacteria and fungi. However, while
      the Raman effect is so weak that only approximately 1 in 10(8) incident photons
      are Raman scattered (so that collection times are in the order of minutes), it
      can be greatly enhanced (by some 10(3)-10(6)-fold) if the molecules are attached
      to, or microscopically close to, a suitably roughened surface, a technique known
      as surface-enhanced Raman scattering (SERS). In this study, SERS, employing an
      aggregated silver colloid substrate, was used to analyze a collection of clinical
      bacterial isolates associated with urinary tract infections. While each spectrum
      took 10 s to collect, to acquire reproducible data, 50 spectra were collected
      making the spectral acquisition times per bacterium approximately 8 min. The
      multivariate statistical techniques of discriminant function analysis (DFA) and
      hierarchical cluster analysis (HCA) were applied in order to group these
      organisms based on their spectral fingerprints. The resultant ordination plots
      and dendrograms showed correct groupings for these organisms, including
      discrimination to strain level for a sample group of Escherichia coli, which was
      validated by projection of test spectra into DFA and HCA space. We believe this
      to be the first report showing bacterial discrimination using SERS.

PMID- 14697031
TI  - Isoelectric point determination of norovirus virus-like particles by capillary
      isoelectric focusing with whole column imaging detection.
AB  - A capillary isoelectric focusing-whole column imaging detection (CIEF-WCID)
      method was used to determine the isoelectric point (pI) of norovirus virus-like
      particles (VLPs). The VLPs were produced from noroviruses that represented the
      two genogroups, genogroup I (Funabashi, Seto, and Norwalk) and genogroup II
      (Hawaii, Kashiwa, and Narita). Using the imaged CIEF-WCID detection technique,
      separation was accomplished using a short (4-5 cm) internally coated capillary
      (100-microm diameter) and a whole-column optical absorption imaging detector
      operated at 280 nm. CIEF-WCID experiments showed the similarity of the pI values
      of VLPs from genogroups I and II, with pI values of 5.9, 5.9, 6.0, and 6.0 for
      Funabashi, Norwalk, Seto, and Hawaii. The two other VLPs displayed pI values of
      5.5 (Kashiwa) and 6.9 (Narita). The VLP peaks were shown to be reproducibility
      resolved. CIEF-WCID shows great promise for norovirus detection in public health,
      clinical, and food safety applications, as CIEF-WCID overcomes several
      limitations of the currently used genetic and immunological methods.

PMID- 14697035
TI  - A glucose biosensor based on surface-enhanced Raman scattering: improved
      partition layer, temporal stability, reversibility, and resistance to serum
      protein interference.
AB  - This work updates the recent progress made toward fabricating a real-time,
      quantitative, and biocompatible glucose sensor based on surface-enhanced Raman
      scattering (SERS). The sensor design relies on an alkanethiolate tri(ethylene
      glycol) monolayer that acts as a partition layer, preconcentrating glucose near a
      SERS-active surface. Chemometric analysis of the captured SERS spectra
      demonstrates that glucose is quantitatively detected in the physiological
      concentration range (0-450 mg/dL, 0-25 mM). In fact, 94% of the predicted glucose
      concentrations fall within regions A and B of the Clarke error grid, making
      acceptable predictions in a clinically relevant range. The data presented herein
      also demonstrate that the glucose sensor provides stable SERS spectra for at
      least 3 days, making the SERS substrate a candidate for implantable sensing.
      Glucose sensor reversibility and reusability is evaluated as the sensor is
      alternately exposed to glucose and saline solutions; after each cycle, difference
      spectra reveal that the partitioning process is largely reversible. Finally, the
      SERS glucose sensor successfully partitions glucose even when challenged with
      bovine serum albumin, a serum protein mimic.

PMID- 14697036
TI  - Synthesis/degradation ratio mass spectrometry for measuring relative dynamic
      protein turnover.
AB  - One of the major unanswered questions in quantitative proteomics is that of
      dynamic protein turnover in the cell. Here we present a new approach to
      quantitative proteomics that measures the relative dynamic turnover of proteins
      in cellular systems. In this approach, termed synthesis/degradation ratio mass
      spectrometry, stable isotope labeling is employed to calculate a relative
      synthesis/degradation ratio that reflects the relative rate at which 13C is
      incorporated into individual proteins in the cell. This synthesis/degradation
      ratio calculation is based on a Poisson distribution model that is designed to
      support high-throughput analysis. Protein separation and analysis is accomplished
      by utilizing one-dimensional SDS-PAGE gel electrophoresis followed by cutting the
      gel into a series of bands for in-gel digestion. The resulting peptide mixtures
      are analyzed via solid-phase MALDI LC-MS and LC-MS/MS using a tandem time-of
      flight mass spectrometer. A portion of the soluble protein fraction from an E.
      coli K-12 strain was analyzed with synthesis/degradation ratios varying from
      approximately 0.1 to 4.4 for a variety of different proteins. Unlike other
      quantitative techniques, synthesis/degradation ratio mass spectrometry requires
      only a single cell culture to obtain useful biological information about the
      processes occurring inside a cell. This technique is highly amenable to shotgun
      proteomics-based approaches and thus should allow relative turnover measurements
      for whole proteomes in the future.

PMID- 14697037
TI  - An analytical device for on-site immunoassay. Demonstration of its applicability
      in semiquantitative detection of aflatoxin B1 in a batch of samples with
      ultrahigh sensitivity.
AB  - A simple analytical device has been developed for performing noninstrumental
      immunofiltration-based assay on a batch of samples. The device consists of
      membrane strips, with antibody-immobilized zones, attached to a polyethylene
      card. A moist filter paper placed between the membrane and the polyethylene card
      acts as the absorbent body. The device was used to estimate very low
      concentrations of aflatoxin B1 (AFB1) present in food samples by using an
      improved catalyzed reporter deposition (Super-CARD) method of signal
      amplification involving biotinylated tyramine (B-T) and avidin-horseradish
      peroxidase conjugate. 4-chloro-1-naphthol was used as the substrate for
      visualization. Semiquantitative results are obtained by visual comparison of the
      color intensity (inversely related to the analyte concentration) of a sample spot
      with those of reference standards. Quantitative estimation is possible by
      densitometric analysis (detection limit 0.25 pg/spot, 0.01 ng mL(-1)). Dilute
      samples can be assayed by in situ concentration with improved dose-response
      characteristics. A batch of 12 extracted samples can be analyzed in a single test
      card within 12 min. Spiked and contaminated samples of groundnut, corn, wheat,
      cheese, and chilli were analyzed without sample cleanup. The matrix interferences
      were eliminated by using appropriate dilution of the aqueous methanol extracts.
      Mean recoveries from different food samples were between 91 and 104%. The values
      obtained for infected corn and groundnut samples correlated well (R2=0.99) with
      the estimates by HPLC. The method is well-suited for visual screening of
      agricultural and food samples for AFB1 under field conditions.

PMID- 14697043
TI  - Biosensor-based determination of riboflavin in milk samples.
AB  - An assay for quantification of riboflavin (Rf) in milk-based products has been
      developed using the principle of surface plasmon resonance with on-chip
      measurement. The quantification was done indirectly by measuring excess of Rf
      binding protein (RBP) that remains free after complexation with Rf molecules
      originally present in the sample solution. The chip was modified with covalently
      immobilized Rf in order to bind the RBP in excess. A chemical modification was
      performed to introduce a reactive ester group at the N-3 position of the natural
      Rf to bind amino groups present on the chip surface. Calibration solutions were
      prepared by mixing a range of Rf standard solutions with an optimized
      concentration of RBP. The Rf content in the milk-based products was then measured
      by comparison of the response against the calibration. Results obtained were very
      close to those from an official HPLC-fluorescence procedure. The limit of
      quantification was determined to 234 microg/L and the limit of detection to 70
      microg/L by an injection volume of 160 microL.

PMID- 14697044
TI  - Ultrasensitive proteomics using high-efficiency on-line micro-SPE-nanoLC-nanoESI
      MS and MS/MS.
AB  - Ultrasensitive nanoscale proteomics approaches for characterizing proteins from
      complex proteomic samples of <50 ng of total mass are described. Protein
      identifications from 0.5 pg of whole proteome extracts were enabled by ultrahigh
      sensitivity (<75 zmol for individual proteins) achieved using high-efficiency
      (peak capacities of approximately 10(3)) 15-microm-i.d. capillary liquid
      chromatography separations (i.e., using nanoLC, approximately 20 nL/min mobile
      phase flow rate at the optimal linear velocity of approximately 0.2 cm/s) coupled
      on-line with a micro-solid-phase sample extraction and a nanoscale electrospray
      ionization interface to a 11.4-T Fourier transform ion cyclotron resonance
      (FTICR) mass spectrometer (MS). Proteome measurement coverage improved as sample
      size was increased from as little as 0.5 pg of sample. It was found that a 2.5-ng
      sample provided 14% coverage of all annotated open reading frames for the
      microorganism Deinococcus radiodurans, consistent with previous results for a
      specific culture condition. The estimated detection dynamic range for detected
      proteins was 10(5)-10(6). An improved accurate mass and LC elution time two
      dimensional data analysis methodology, used to both speed and increase the
      confidence of peptide/protein identifications, enabled identification of 872
      proteins/run from a single 3-h nanoLC/FTICR MS analysis. The low-zeptomole-level
      sensitivity provides a basis for extending proteomics studies to smaller cell
      populations and potentially to a single mammalian cell. Application with ion trap
      MS/MS instrumentation allowed protein identification from 50 pg (total mass) of
      proteomic samples (i.e., approximately 100 times larger than FTICR MS),
      corresponding to a sensitivity of approximately 7 amol for individual proteins.
      Compared with single-stage FTICR measurements, ion trap MS/MS provided a much
      lower proteome measurement coverage and dynamic range for a given analysis time
      and sample quantity.

PMID- 14697046
TI  - A self-catalytic carbon paste electrode for the detection of vitamin B12.
AB  - A simple, sensitive, and selective method for the detection of vitamin B12
      (cyanocobalamin) is presented. A carbon paste electrode has been constructed with
      trans-1,2-dibromocyclohexane (DBCH) acting as both the paste binder and a
      reactive material facilitating the electrocatalytic detection of the target. The
      latter reaction is based on the electroreduction of the Co(III) center in vitamin
      B12 to Co(I), which specifically reacts with DBCH to produce electrocatalytic
      currents with the regeneration of Co (II); a detection limit of 8.5 x 10(-10) mol
      dm(-3) (based on 3sigma) was found. The electrode has been successfully used for
      the quantification of vitamin B12 in pharmaceutical products and biological
      matrix media.

PMID- 14697048
TI  - Subnanomolar cyanide detection at polyphenol oxidase/clay biosensors.
AB  - A novel, inexpensive, and simple amperometric biosensor based on immobilization
      of polyphenol oxidase (PPO) into Zn-Al layered double hydroxides, also called
      anionic clays, is applied for determination of cyanide. The detection of cyanide
      was performed via its inhibiting action on the PPO electrode. Measurement was
      carried out with 3,4-dihydroxyphenylacetic acid as enzyme substrate, the
      enzymatically generated quinoid products being electroreduced at -0.2 V. An
      extremely sensitive detection limit (0.1 nM) was obtained for cyanide. Enzyme
      immobilization into an anionic exchanger clay seems to cause an increase in
      cyanide inhibition effects because of anion accumulation in the clay matrix.

PMID- 14697050
TI  - Separation of long double-stranded DNA by nanoparticle-filled capillary
      electrophoresis.
AB  - We present the first example of the analysis of long double-stranded (ds) DNA
      molecules by nanoparticle-filled capillary electrophoresis (NFCE). To avoid
      aggregation of the gold nanoparticles (GNPs) and to allow strong interactions
      with the DNA molecules, the gold nanoparticles were modified with poly(ethylene
      oxide) (PEO) via noncovalent bonding to form gold nanoparticle/polymer composites
      (GNPPs). The neutral GNPPs are heavy (approximately 2.0 x 10(8) g/mol for the 32
      nm GNP) and thus slow the DNA molecules that they encounter during the
      electrophoretic process. Compared to linear polymer solutions, such as
      hydroxyethyl cellulose and PEO, the GNPPs provide greater efficiency and require
      significantly shorter times to separate long dsDNA. The separation of lambda-DNA
      (0.12-23.1 kbp) by NFCE at -250 V/cm was accomplished in 3 min. The ability to
      separate high molecular weight DNA markers (8.27-48.5 kbp) with plate numbers
      greater than 10(6) suggests that this novel method may hold great promise for the
      analysis of long-stranded DNA molecules such as chromosomes. Moreover, this
      method is simple and affordable when compared to those that use micro- and
      nanofabricated devices for separating long DNA molecules.

PMID- 14697051
TI  - Heterogeneous adsorption of 1-indanol on cellulose tribenzoate and adsorption
      energy distribution of the two enantiomers.
AB  - The distributions of the adsorption energies (AED) of two enantiomers, (R)-1-
      indanol and (S)-1-indanol, on a chiral stationary phase were measured and the
      results are discussed. The chiral phase used is made of cellulose tribenzoate
      coated on porous silica. The AEDs were determined using the expectation
      maximization method, a numerical method that uses directly the raw experimental
      isotherm data, inverts this set of data into an AED, and introduces no arbitrary
      information in the calculation. However, it uses the Langmuir equation as the
      local isotherm. The experimental data fit very well to the bi-Langmuir isotherm
      model for the more retained enantiomer. Our results show that the AEDs of these
      two enantiomers have no energy modes that would be identical (same mean energy,
      mode profile, and mode area), in contrast to numerous cases previously studied,
      e.g., that of the beta-blockers on a Cel7A column. This indicates a significantly
      different retention mechanism.

PMID- 14697052
TI  - Screening and identification of acidic carbohydrates in bovine colostrum by using
      ion/molecule reactions and Fourier transform ion cyclotron resonance mass
      spectrometry: specificity toward phosphorylated complexes.
AB  - A screening method was developed for the identification of acidic saccharides
      from biological mixtures utilizing gas-phase derivatization and mass
      spectrometry. Phosphorylated compounds were differentiated from other acidic
      species by exploiting the selective reactivity of chlorotrimethylsilane with the
      phosphate ions (phosphorylated compounds shift by 72 Da, allowing rapid compound
      detection). A 13-component mock mixture was used to demonstrate the viability of
      the method, and a detection limit of 600 nM (30 fmol) was determined. This method
      was applied to the identification of acidic compounds from bovine colostrum. To
      further verify the selectivity of the ion/molecule reaction, exact mass
      measurements were used to determine the elemental composition of 14 compounds.
      Eight novel acidic carbohydrate species were observed in bovine colostrum, six of
      which have never been reported previously in milks. Tandem mass spectrometric
      experiments allowed compound characterization for two of these components.

PMID- 14697053
TI  - The nature of phosphorylated chrysin-protein interactions involved in noncovalent
      complex formation by electrospray ionization mass spectroscopy.
AB  - In the work described in this paper, chrysin was phosphorylated by a modified
      Atheron-Todd reaction. The structure of phosphorylated chrysin was determined by
      elemental analysis, NMR, ESI-MS/MS, and X-ray data. Electrospray ionization
      results showed that the phosphorylated flavonoids could form noncovalent
      complexes with many proteins, such as lysozyme, myoglobin, bovine insulin, and
      cytochrome c, while noncovalent complexes were not detected in the mixed solution
      of the chrysin and proteins. The research shows that the phosphorylated
      flavonoids possess relatively stronger affinities and form noncovalent complexes
      with the proteins more easily than the non-phosphorylated compounds.

PMID- 14697054
TI  - Positively charged sol-gel coatings for on-line preconcentration of amino acids
      in capillary electrophoresis.
AB  - A novel on-line method is presented for the extraction and preconcentration of
      amino acids using a sol-gel-coated column coupled to a conventional UV/visible
      detector. The presented approach does not require any additional modification of
      the commercially available standard CE instrument. Extraction, stacking, and
      focusing techniques were used in the preconcentration procedures. Sol-gel
      coatings were created by using N-octadecyldimethyl[3
      (trimethoxysilyl)propyl]ammonium chloride (C18-TMS) in the coating sol solutions.
      Due to the presence of a positively charged quaternary ammonium moiety in C18
      TMS, the resulting sol-gel coating carried a positive charge. For extraction, the
      pH of the samples was properly adjusted to impart a net negative charge to amino
      acids. A long plug of the sample was then passed through the sol-gel-coated
      capillary to facilitate extraction via electrostatic interaction between the
      positively charged sol-gel coating and the negatively charged amino acid
      molecules. Focusing of the extracted amino acids was accomplished through
      desorption of the extracted amino acid molecules carried out by local pH change.
      Two different methods are described. Both methods showed excellent extraction and
      preconcentration effects. Preconcentration results obtained on sol-gel-coated
      columns were compared with the CZE analysis performed on bare fused-silica
      columns with traditional sample injections. The described procedure provided a
      150,000-fold enrichment effect for alanine. The two methods provided acceptable
      repeatability in terms of both peak height and migration time.

PMID- 14697055
TI  - Two-step liquid-liquid-liquid microextraction of nonsteroidal antiinflammatory
      drugs in wastewater.
AB  - A simple and novel two-step liquid-liquid-liquid microextraction technique
      combined with reversed-phase HPLC has been developed for the determination of the
      nonsteroidal antiinflammatory drugs ibuprofen and 2-(4-chlorophenoxy)-2
      methylpropionic acid in wastewater samples. In the first step, the analytes were
      extracted from an acidified sample (donor solution) into 1-octanol immobilized in
      the pores of 10 pieces of polypropylene hollow fiber and further into a basic
      acceptor phase inside the hollow fiber channels. This first extraction step,
      using 0.01 M NaOH as the acceptor phase and 0.1 M HCl within the donor phase, had
      a 100% relative recovery with an enrichment factor of 100-fold. The extract in
      the first step was then adjusted to acidic condition with HCl. It now represented
      the donor phase for the second step of the extraction, using a single piece of
      hollow fiber, with 2 microL of 0.01 M NaOH solution as the acceptor phase. This
      analyte-enriched acceptor phase was subsequently withdrawn into a microsyringe
      and directly injected into an HPLC system for analysis. With this two-step
      microextraction, sensitivity enhancement of >15,000-fold could be obtained.
      Detection limits of < or =100 ng/L could be achieved for both compounds. The
      method was applied to the analysis of wastewater.

PMID- 14697056
TI  - Enzymatic probe sonication: enhancement of protease-catalyzed hydrolysis of
      selenium bound to proteins in yeast.
AB  - This paper describes the dramatic activity enhancement of two proteolytic enzymes
      (protease XIV and subtilisin) when treated with an ultrasonic probe and their
      application to total Se determination and Se speciation in biological samples.
      Total Se extraction from enriched yeast is performed with 10 mg of yeast plus 1
      mg of protease with a sonication time of 5 s, whereas 30 s is needed for
      extracting selenomethionine. In both cases, aqueous media was used. This
      spectacular finding is important because the enzymatic procedure usually requires
      a long treatment period at 37 degrees C. In addition to this major advantage, no
      control temperature is needed and the risk of species interconversion is
      drastically reduced or inhibited (the same Se species were detected after
      different sonication times). Moreover, the extraction is performed in water,
      minimizing contamination risk and without further pH adjustment. The new sample
      treatment proposed has been successfully applied to selenium speciation in yeast
      using chromatographic separation (HPLC) coupled to inductively coupled plasma
      mass spectrometry.

PMID- 14697059
TI  - Submucous cleft with a perforation not "rarely" reported.

PMID- 14697060
TI  - The use of tongue-lip adhesions in the surgical treatment of Robin sequence.

PMID- 14697062
TI  - The use of tongue-lip adhesions in the surgical treatment of Robin sequence.

PMID- 14697063
TI  - Management of craniofacial development in the Parry-Romberg syndrome: report of
      two patients.
AB  - OBJECTIVE: The aim of this article is to describe the orthodontic therapy for
      Parry-Romberg syndrome. The therapeutic goal is to minimize the wasting effects
      of progressive atrophy on facial development of a part of the face. DESIGN: To
      correct problems affecting craniofacial development of these patients, occurring
      during puberty, an orthodontic appliance was employed, which helps maintain
      parallelism of the facial planes, in particular the mandibular plane. SETTING:
      Orthodontic care was carried out in the Dental Clinic of the Catholic University
      of the Sacred Heart of Rome. INTERVENTION: Two patients underwent orthodontic
      therapy for 6 years. Appliances were checked every month and modified
      periodically so as to adapt to facial bone growth. RESULTS: At the end of
      craniofacial growth, the mandible was almost symmetric and the problem relating
      to atrophy remained confined to the initial area. Cephalometric analyses
      demonstrated that the occlusal plane and the mandibular plane maintained a
      straight orientation in relation to the bizygomatic plane. The ratio between the
      left and right side of the ramus and condyle, in the mandible, improved.
      CONCLUSIONS: The use of orthodontic therapy allows patients affected by
      hemifacial progressive atrophy to present a more harmonic face at the end of
      puberty when final reconstruction can be planned. These results provide for a
      limitation of surgical intervention to the sclerodermic area alone.

PMID- 14697064
TI  - A case of oculo-facio-cardio-dental syndrome with integrated orthodontic
      prosthodontic treatment.
AB  - OBJECTIVE: Oculo-facio-cardio-dental (OFCD) syndrome is a very rare condition
      that requires comprehensive dental management because of associated multiple
      dental anomalies such as canine radiculomegaly, delayed dentition, oligodontia,
      persistent primary teeth, microdontia, and macrodontia. This report presents a
      case of OFCD in a Japanese girl (13 years 1 month old). We analyzed cephalograms,
      panoramic roentgenograms, and dental casts and discuss our integrated orthodontic
      prosthodontic treatment. DESIGN: The sizes of the tooth crown and root as well as
      lateral cephalograms were compared with those from a Japanese control group. The
      outcome of orthodontic treatment was evaluated by comparing cephalograms taken
      before and after treatment. RESULTS: Radiculomegaly was found not only in the
      upper and lower canines but also the upper central incisors and lower first
      premolars. Macrodontia was found in the upper central incisors, upper canines,
      lower canines, and lower first premolars. Microdontia was found in the upper
      lateral incisor. Lateral cephalometric analysis showed a remarkable hypoplastic
      midface in both the sagittal and vertical dimensions, coupled with a
      significantly decreased cranial base length and an increased gonial angle. Serial
      lateral cephalograms during orthodontic treatment from 13 to 23 years of age
      demonstrated only slight maxillary growth and significant downward mandibular
      growth with clockwise rotation in addition to pronounced labial tipping of the
      upper central incisors. CONCLUSIONS: Characteristic dental anomalies together
      with a unique craniofacial dysmorphology were clarified. Successful oral
      rehabilitation was achieved by integrated orthodontic-prosthodontic treatment.

PMID- 14697065
TI  - Choanal atresia and rare craniofacial clefts: report of three cases with a review
      of the literature.
AB  - OBJECTIVE: This retrospective study reports three cases associating choanal
      atresia (CA) and rare craniofacial clefts (RCFCs) described in Tessier's
      classification. Although still discussed, these two malformations could derive
      from the same embryopathogenic context, with an anomaly of migration of the
      neural crest cells as a common factor. In two of the three cases presented, the
      RCFC was diagnosed during the neonatal period, and the third case (case 3) was
      diagnosed at the age of 12 years. The knowledge of this malformative association
      must permit the diagnosis of CA as early as the neonatal period or through the
      thorough and directed examination of the children as part of the follow-up.

PMID- 14697066
TI  - Cost-effectiveness of infant orthopedic treatment regarding speech in patients
      with complete unilateral cleft lip and palate: a randomized three-center trial in
      the Netherlands (Dutchcleft).
AB  - OBJECTIVE: To investigate the cost-effectiveness of infant orthopedic treatment
      (IO), compared with no such treatment in children with complete unilateral cleft
      lip and palate (UCLP) focusing on the effects on speech development at age 2.5
      years. DESIGN: In a three-center prospective, randomized clinical trial
      (Dutchcleft), two groups of children with complete UCLP were followed
      longitudinally: one group was treated with IO based on a modified Zurich approach
      in the first year of life (IO group) and the other group did not receive this
      treatment (non-IO group). PATIENTS: The participants had complete UCLP without
      soft tissue bands or other malformations. They were born at term and their
      parents were native Dutch speakers. OUTCOME MEASURES: The effect of IO on speech
      development at age 2.5 years was measured blindly by five expert listeners
      judging the "total impression of speech quality" on a 10-point equal-appearing
      interval scale. Costs were measured from a societal viewpoint in Euro. RESULTS
      AND CONCLUSION: The IO group (n = 10) obtained a statistically significant higher
      rating, compared with the non-IO group (n = 10). The effect size was large,
      indicating that the improvement may be considered a clinically important change.
      The cost for treatment by the orthodontist was higher in the IO group. For both
      groups, the mean cost was related to the mean rating for "total impression of
      speech quality." The resulting cost-effectiveness for IO, compared to non-IO was
      1041 for 1.34 point speech quality improvement. The financial investment that is
      necessary to obtain this improvement seems limited. Thus, from the perspective of
      speech development, the cost-effectiveness of IO over non-IO seems acceptable at
      this point in time.

PMID- 14697067
TI  - Methodology for perceptual assessment of speech in patients with cleft palate: a
      critical review of the literature.
AB  - OBJECTIVE AND DESIGN: This review of 88 articles in three international journals
      was undertaken for the purpose of investigating the methodology for perceptual
      speech assessment in patients with cleft palate. The articles were published
      between 1980 and 2000 in the Cleft Palate-Craniofacial Journal, the International
      Journal of Language and Communication Disorders, and Folia Phoniatrica et
      Logopaedica. RESULTS AND CONCLUSIONS: The majority of articles (76) were
      published in the Cleft Palate-Craniofacial Journal, with an increase in articles
      during the 1990s and 2000. Information about measures or variables was clearly
      given in all articles. However, the review raises several major concerns
      regarding method for collection and documentation of data and method for
      measurement. The most distressing findings were the use of a cross-sectional
      design in studies of few patients with large age ranges and different types of
      clefts, the use of highly variable speech samples, and the lack of information
      about listeners and on reliability. It is hoped that ongoing national and
      international collaborative efforts to standardize procedures for collection and
      analysis of perceptual data will help to eliminate such concerns and thus make
      comparison of published results possible in the future.

PMID- 14697068
TI  - Oral health of individuals with cleft lip, cleft palate, or both.
AB  - OBJECTIVE: To evaluate the oral health of children with cleft lip and palate.
      DESIGN: DMFT (dmft) and DMFS (dmfs) were calculated on the basis of visual
      examination. Periodontal disease was assessed by classical clinical parameters:
      volume gain, bleeding, probing depth, loss of insertion, gingival recession. and
      calculus. PATIENTS: Seventy-eight individuals aged 1 to 32 years took part in the
      study. RESULTS: The dmft was 2.91 (+/- 3.99) in the 1- to 5-year-old age group
      and 2.77 (+/- 3.15) in the 6- to 12-year-old group. The DMFT averages for the age
      groups of 6 to 12 years, 13 to 18 years, and 19 to 32 years were 1.87 (+/- 1.78),
      6.46 (+/- 3.11), and 13.62 (+/- 6.51), respectively. A total of 5.3% of
      individuals presented a healthy periodontium, and 86.6% presented with gingivitis
      and 8% presented with periodontitis. CONCLUSIONS: The dental and periodontal
      condition of individuals with cleft lip and palate was similar to the general
      population in the region in which this study was conducted. Good preventive
      measures should result in improved oral health similar to the general population
      and should be emphasized.

PMID- 14697069
TI  - Growth of children with isolated Robin sequence treated by nasopharyngeal
      intubation: importance of a hypercaloric diet.
AB  - OBJECTIVE: To compare the growth curves (weight and length) of two groups of
      infants with isolated Robin sequence (RS) treated with nasopharyngeal intubation
      (NPI), one group receiving a hypercaloric diet and the other receiving a normal
      diet for age, and compare the growth rates and duration of NPI between the two
      groups. DESIGN: Prospective longitudinal study. SETTING: Hospital de Reabilitacao
      de Anomalias Craniofaciais, Universidade de Sao Paulo, Bauru, Brazil, 1998 to
      2000. PATIENTS: Twenty-three children with isolated RS treated by prolonged NPI.
      INTERVENTIONS: Nine children received a milk formula supplemented with 5% to 7%
      glucose polymers and 3% to 5% medium chain triglycerides (group 1), and 14
      children received a milk formula only (group 2). Weight and length were measured
      at birth and every month up to 6 months of life for the construction of weight
      and length growth curves. The time of use of the nasogastric tube, age at the
      beginning of NPI, and duration of NPI were also determined. RESULTS: No
      significant difference in length was observed between the two groups. The mean
      weight curves obtained for the two groups were below the 50th percentile of the
      National Center for Health Statistics, but weight gain was higher in group 1. The
      duration of NPI was shorter in this group. CONCLUSIONS: The hypercaloric diet led
      to an improvement in nutritional status, which in turn contributed to improved
      respiratory conditions in isolated RS.

PMID- 14697070
TI  - Pierre Robin sequence in Denmark: a retrospective population-based
      epidemiological study.
AB  - OBJECTIVE: To give an epidemiological description of the clinical entity given
      the name Pierre Robin sequence, defined by retro- and micrognathia, cleft palate,
      and respiratory distress and describe other malformations and possible
      intrauterine impairment. METHODS: Using the inclusion criteria of micrognathia,
      cleft palate, and neonatal respiratory distress, a retrospective population-based
      study of all Danish live births during 1990 through 1999 were carried out. We
      found 50 children, 25 boys and 25 girls, fulfilling the inclusion criteria,
      giving an incidence of 1 in 14,000 live births. RESULTS: Two-thirds (n = 33) of
      the children had the classical U-shaped cleft palate. More than one-third (n =
      19) had one or several other malformations, and in five patients the triad of
      Pierre Robin was a minor feature of a complex syndrome. The most common
      noncomplex syndrome was the Stickler syndrome found in 6 of the 50 patients. More
      than one-fourth (n = 17) had some kind of intrauterine impairment, with no
      specific obstetric diagnosis predominant. Consistent with this, the average birth
      weight was well below normal. CONCLUSIONS: Several authors have stated that the
      triad of Pierre Robin is not a nosological entity, in that it has diverse
      etiology and diverse pathogenesis. We conclude that the triad of Pierre Robin
      still can be regarded as a clinical entity, readily defined at birth,
      experiencing the same neonatal problems in varying degrees and hence the
      possibility of designing treatment protocols for later scientific evaluation.

PMID- 14697071
TI  - A comparison of craniofacial form in Northern Irish children with unilateral
      cleft lip and palate treated with different primary surgical techniques.
AB  - OBJECTIVE: The quality of outcomes in patients with unilateral cleft lip and
      palate (UCLP) was compared between two senior plastic surgeons. One surgeon
      carried out a one-stage Wardill-Kilner palate repair. The other surgeon employed
      a vomer flap hard palate repair followed by a von Langenbeck soft palate closure
      (Oslo protocol). DESIGN: Retrospective analysis. PATIENTS: Thirty-four children
      (mean age 9.7 years) born with complete skeletal UCLP in Northern Ireland from
      1983 to 1991 who received primary repair surgery from one of the two surgeons.
      MAIN OUTCOME MEASURES: Cephalometric analysis was used to determine the
      craniofacial form and soft tissue profile. The quality of the dental arch
      relationships was independently assessed using the Goslon ranking system.
      RESULTS: Twenty-nine of the 34 subjects had good or satisfactory arch
      relationships. Comparison between the surgeons revealed that the Wardill-Kilner
      group had a greater proportion of Goslon grades of greater than 3, indicating
      poor arch relationships. However, this difference failed to reach statistical
      significance. There were no significant cephalometric differences between
      patients treated by the two surgeons. CONCLUSIONS: Although the difference was
      not statistically significant, the highest proportion of patients likely to
      require orthognathic surgery was found in those treated using the Wardill-Kilner
      technique.

PMID- 14697072
TI  - Alveolar ridge notching as a predictor for secondary bone grafting in incomplete
      alveolar clefts.
AB  - OBJECTIVES: To clarify the need for secondary alveolar bone grafting (ABG) in
      incomplete alveolar clefts identified clinically from its appearance and test the
      usefulness of alveolar ridge notching in the edentulous stage as a predictor for
      ABG. DESIGN: A prospective, cross-sectional study comparing three groups of
      patients at two stages. PATIENTS: Twenty-four patients with unilateral incomplete
      cleft of primary palate who underwent either no surgery or cheiloplasty only.
      METHODS: Cleft severity was assessed at two stages. Initially, the appearance of
      untreated clefts was assessed before cheiloplasty or at 3 months of age in the
      patient without cheiloplasty and graded by severity into three groups. Later
      alveolar bone defects were assessed with computed tomography in the primary or
      mixed dentition period. A decision regarding the requirement for ABG was then
      made. Finally, the relationship between untreated clefts and the need for ABG was
      determined. MAIN OUTCOME MEASURES: Nine (75%) of 12 patients with alveolar ridge
      notching in the edentulous stage were diagnosed as fulfilling the criteria for
      ABG. RESULTS: The alveolar bone defects correlated with the severity of untreated
      cleft conditions (Spearman r = 0.65, p =.002). The need for ABG was greater in
      patients with alveolar ridge notching, compared with those without notching (9/12
      versus 0/12, p =.00034). CONCLUSIONS: Most patients with incomplete alveolar
      clefts clinically identified in the edentulous stage required ABG, and alveolar
      ridge notching in the edentulous stage could therefore serve as a predictor for
      ABG.

PMID- 14697073
TI  - Facial characterization of infants with cleft lip and palate using a three
      dimensional capture technique.
AB  - OBJECTIVE: To characterize the soft tissue features of infants with unilateral
      cleft lip (UCL) and unilateral complete cleft lip and palate (UCLP) prior to
      primary surgery and compare with noncleft controls. DESIGN: Prospective
      controlled capture of the facial morphology of infants using a noninvasive three
      dimensional stereophotogrammetry method. PARTICIPANTS: 23 children with
      presurgical cleft: 11 UCL (M = 6, F = 5); 12 UCLP (M = 9, F = 3), and 21 noncleft
      controls (M = 7, F = 14) were imaged at approximately 3 months of age (range 10
      to 16 weeks). MAIN OUTCOME MEASURE: Accurate, repeatable quantification of facial
      soft tissues in infants with clefts prior to surgery. RESULTS: Significant
      differences (p <.05) were found between the UCLP group and UCL and control groups
      in anatomical and soft nose width, cleft-side alar wing length, and nasal tip
      horizontal displacement. Both cleft groups were significantly different from
      controls and from each other in cleft-side nostril dimensions, alar wing
      angulation, columella angle, and alar base to corner of mouth dimension; alar
      base width; and soft tissue defect in nose and the lip and philtrum length
      bordering the cleft. Significant differences between clefts and controls were
      identified in the nostril and philtrum on the noncleft side. CONCLUSIONS: The use
      of children with UCL as controls for UCLP studies is inappropriate. This
      technique overcame the limitations of direct measurement of infant faces to aid
      the surgeon in the planning and subsequent re-evaluation of surgical rationale.

PMID- 14697074
TI  - Three-dimensional analysis of maxillary dental casts using Fourier transform
      profilometry: precision and reliability of the measurement.
AB  - OBJECTIVE: Fourier transform profilometry was used for the three-dimensional
      measurement of maxillary dental casts to analyze the size and shape of the
      palate. The objective of this study was to test the accuracy of the measuring
      system and determine the precision and reliability of the measurement METHODS:
      Images of dental casts were analyzed using newly developed measuring software.
      Based on five landmarks located on the alveolar ridge, the measuring software
      constructed 10 transversal sections of the palate. In each section profile, the
      width, area, and 23 height variables were assessed. SUBJECTS: Maxillary dental
      stone casts of 25 healthy girls, 14.1 to 15.3 years of age, were studied.
      RESULTS: The technical error of measurement exceeded 5% of the size of the
      measurement only in variables with means less than approximately 3 mm. In fact,
      such small absolute dimensions were exhibited only by the palate height in
      anterior profile 2 and the palate height at the margins of other profiles.
      Reliability of the measurements was found to be very high for the width and area
      of the profiles. For height measurements, the coefficient of reliability was
      slightly lower at the profile margins than near the midline. Nevertheless, only
      three height variables showed a coefficient of reliability lower than 0.90. The
      coefficients of reliability of other height measurements of profiles 3 through 10
      were only sporadically lower than 0.97. CONCLUSION: With regard to the accuracy
      of the measuring system as well as the precision and reliability of the
      measurement, this method proved to be a suitable tool for studying palatal
      morphology.

PMID- 14697075
TI  - Differential diagnosis of the trapezoid-shaped head.
AB  - OBJECTIVE: To recognize several conditions that result in a trapezoid head shape
      and review and contrast their various physical findings. METHODS: A detailed
      review of all patients seen in the Craniofacial Clinic at the Children's Hospital
      and Regional Medical Center in Seattle, Washington, over a 10-year period from
      1991 to 2001, with the diagnosis of craniosynostosis and plagiocephaly was
      performed. During this period, 690 patients had a surgical correction of
      craniosynostosis, and 1537 patients had posterior plagiocephaly. RESULTS AND
      CONCLUSIONS: The shape of the head when viewed from the vertex position in an
      axial plane can be a significant diagnostic aid when evaluating a patient with
      plagiocephaly. Positional molding causes the vast majority of plagiocephaly. This
      deformational change results in a parallelogram-shaped head. A much more rare
      cause of plagiocephaly is lambdoid synostosis. With premature fusion of one of
      the lambdoid sutures, the head takes on a very characteristic trapezoid shape
      when viewed from the vertex. Unilateral coronal synostosis that occurs on the
      same side as either posterior positional molding or unilateral lambdoid
      synostosis will also result in the trapezoid head shape. Furthermore, on the rare
      occasion when anterior and posterior deformational plagiocephaly occurs on the
      same side, the trapezoid head shape may be the consequence. The choice of
      appropriate treatment modality requires systematic evaluation of the patient with
      a trapezoid-shaped head to determine the etiology of the deformation.

PMID- 14697076
TI  - Correction of facial asymmetry with multiplanar mandible distraction: a one-year
      follow-up study.
AB  - OBJECTIVE: To assess the effectiveness of multiplanar mandibular distraction by
      evaluating the treatment effect and 1-year stability, measuring changes on the
      affected and nonaffected sides, and evaluating correction of the occlusal plane
      and oral commissure cant. PATIENTS AND METHOD: Eleven patients aged 5 to 9.4
      years (mean 6.7 years ) who underwent unilateral multiplanar mandibular
      distraction were included, 10 with hemifacial microsomia and one
      temporomandibular joint ankylosis. Intermaxillary elastics were applied to
      intraoral dental devices during and after distraction until bony consolidation
      and occlusal interdigitation were achieved. Radiographs were taken and measured
      before distraction, after vertical distraction, after completion of distraction,
      and 1 year after treatment. Frontal facial photographs were obtained to analyze
      the changes in the position of the oral commissure. RESULTS: The facial profile
      was improved by sagittal mandibular advancement. Although the facial height
      increased 6.6 mm during vertical distraction, with a net gain of 5.8 mm in follow
      up, the mandibular plane angle was maintained. The affected mandibular length
      increased 8.3 mm after distraction and remained unchanged after 1 year. Ramus
      height increased 12.7 mm after distraction and relapsed 3.8 mm at follow-up
      (30%). The affected body length demonstrated postoperative growth of 3.1 mm.
      Correction of the chin deviation was 9.8 mm after distraction and relapsed 1.6 mm
      (16.3%) after 1 year. Canting of the occlusal plane and oral commissure was
      corrected and remained stable. CONCLUSION: Multiplanar mandibular distraction is
      an effective treatment for correcting facial asymmetry in young children. The 1
      year follow-up revealed that the new sagittal jaw relation and mandibular body
      length were stable, and the achieved occlusal interdigitation was well
      maintained. However, the ramus height and chin deviation demonstrated some
      relapse.

PMID- 14697077
TI  - Veloplasty using the wave-line technique versus classic intravelar veloplasty.
AB  - OBJECTIVE: A well-known problem in primary surgery of the soft palate is its
      shortness and the deficit of local soft tissue. This article introduces a
      modification of the primary intravelar veloplasty, allowing lengthening of the
      soft palate, and compares this alternative technique to the classic intravelar
      veloplasty. METHOD: The soft palate wave-line technique adds a wavy incision at
      the velar cleft margins to the intravelar veloplasty. In 24 patients with
      complete clefts of the palate, either the newly developed or classic technique
      was performed. Four years following primary surgery, speech performance and type
      of breathing were analyzed. RESULTS: Even in wide clefts of the soft palate,
      repair was easily accomplished using the wave-line technique. Complete closure of
      the nasal, muscular, and oral layers was achieved, and no postoperative fistula
      was observed. An average lengthening of the soft palate of 56% (range 24% to 83%)
      was observed immediately following velar repair with the wave-line technique.
      Speech was significantly better in the wave-line group (p <.05). Furthermore,
      physiological breathing was observed more often in these patients. CONCLUSION:
      Primary repair of clefts of the soft palate using the wave-line technique is
      straightforward, safe, and easy. On the basis of the present results, this
      technique seems superior to the classic intravelar veloplasty.

PMID- 14697078
TI  - [Hepcidin, a new protein of body iron homeostasis].

PMID- 14697079
TI  - [Quality study of diagnostic and follow-up procedures of bone involvement in type
      1 Gaucher"s disease in Spain].
AB  - BACKGROUND: Bone involvement in type 1 Gaucher"s disease can be devastating and
      is oftenly silent. Bone MR is generally recommended. The aim of the study was to
      elucidate whether the size and location of hospitals in Spain implies any
      difference in management of GD patients. MATERIAL AND METHODS: We surveyed the
      type of facilities in the hospital (namely MRI) as well as for the presence,
      type, severity and methodology of follow-up of bone involvement associated to GD,
      according to the category of hospital (local or reference). RESULTS: 31 patients
      were followed in reference hospitals whereas 16 other were in local hospitals.
      70% of cases had some type of bone involvement, 60% had severe bone disease. MRI
      was the first choice for diagnosis in 65% and for follow-up in 93% of cases. MRI
      is less indicated among patients from local hospitals. Chitotriosidase is
      measured in a high, but insufficient, proportion of the followed patients (60%).
      CONCLUSIONS: The Spanish hospital network, either reference or local hospitals,
      have an adequate infrastructure for the management of GD patients. However, main
      diagnostic resources are being currently underused.

PMID- 14697080
TI  - [Varicella pneumonia in adults: 30 cases].
AB  - OBJECTIVES: During the past 10 years, 30 adults (age > 15 years) were treated for
      varicella pneumonia in our centre. METHODS: There were 16 males and 14 females.
      Ages ranged from 15 to 58 years (mean, 32.73+/-7.67 years). Twenty-seven patients
      (90%) were non-pregnant adult smokers and three patients (10%) were pregnant
      women. The hospital stay ranged from 4 to 57 days (mean, 14.96+/-12.02 days).
      RESULTS: Seven patients (23.3%) were managed in the intensive care unit and two
      patients (6,6%) required mechanical ventilation. The most common radiographic
      findings were interstitial infiltrates in twenty-one patients (70%) and
      interstitial-alveolar infiltrates in seven patients (23.3%). Physical examination
      of the chest did not reveal abnormalities in twenty patients (66,6%). Fifteen
      patients (50%) were severely hipoxic with pO2/FiO2 ratio less than 300. Twelve
      patients (40%) presented thrombocytopenia and fifteen (50%) presented
      hyponatremia. The most frequent clinical features included: fever (100%), dry
      cough (86.6%), dysnea (66.6%) and chest pain (50%). One patient (3.3%) died.
      Three patients (10%) developed asthma and one other patient developed pulmonary
      fibrosis. CONCLUSIONS: Smoking is associated with an increase incidence of
      varicella pneumonia in adults. A chest x-ray should be practised in all cases of
      varicella in adults and they all should also be admitted to hospital. Intravenous
      aciclovir is recommended for treatment of varicella pneumonia in adults and in
      seriously ill patients the association of corticosteroids should be considered.

PMID- 14697081
TI  - [Sarcoidosis in a sanitary area at Leon (Spain). Epidemiology and clinical
      features].
AB  - BACKGROUND: The incidence of sarcoidosis is different among distincts geographic
      areas, probably due to climate variations. At present, there is in Spain few
      studies that correlate the observed cases with a concrete population. The aim of
      this study is to investigate the epidemiology of sarcoidosis in Leon"s sanitary
      area, in comparison with others spanish geographic areas. Moreover, we present a
      description of the clinic and radiologic characteristics of the studied cases.
      METHOD: We analyzed the cases of sarcoidosis attended in the area from 1993 until
      2001. The incidence, age, sex, place of residence and clinic-radiologic
      characteristics are described. The population data of the sanitary area to
      calculate the incidence were obtain from the Insalud"s data base. The climatology
      values were collected from the National Institute of Meteorology. RESULTS: The
      incidence of sarcoidosis in Leon"s sanitary area was 1,37/100.000 habitants/year,
      and was similar to that founded in Catalonia, Galizia and others provinces of the
      Castilla and Leon community. We observed a higher incidence of sarcoidosis in
      female patients, because of predominance of cases among women aged forty years or
      more. No differences between rural and urban populations were founded. The
      clinical characteristics were similar those described in other geographics areas
      of our country. CONCLUSION: Although there are climate differences between the
      geographics areas of Spain, these aren"t enough to explain his influence in the
      incidence of sarcoidosis, which is similar in all of them, at least in the middle
      north of the country.

PMID- 14697082
TI  - [Intestinal invagination in adult patients due to jejunal tumor with neural
      differentiation of autonome system (GAN)].
AB  - We report two clinical cases of intestinal invagination due to jejunal GAN tumors
      that were operated on because of an intestinal obstruction. Diagnostic methods,
      differential diagnosis and therapeutic approach were analysed.

PMID- 14697083
TI  - [Pseudo-obstruction chronic disease, lymphoid hyperplasia of the gastrointestinal
      tract and intestinal endometriosis].
AB  - Nodular lymphoid hyperplasia of the gastrointestinal tract associated to
      endometriosis is an uncommon cause of chronic pseudo-obstruction and
      malabsortion. The case of a 32-year-old woman who suffered from this syndrome for
      one a half years is described. Diagnosis was achieved by laparotomy, which
      disclosed swelling and inflammation of the 30 cm terminal yeyunal portion.
      Removal of the involved intestine and side-to-side anastomosis were performed.
      The pathological findings were: follicular lymphoid hyperplasia with mucosal
      ulcers an fissures inflammatory pseudo-polyps, chronic deep enteritis and areas
      of endometriosis. A favourable outcome followed surgery.

PMID- 14697084
TI  - [Triiodothyronine intoxication. A clinical and phamacokinetic study].
AB  - A woman, thyroidectomised because of a thyroid papillary carcinoma, interrupted
      temporarily her levothyroxine intake in order to be subjected to an extension
      study five weeks later. To minimise her symptoms for the first three weeks, a
      treatment was prescribed consisting of one 25 micro g-capsule of triiodothyronine
      every 8 hours. Nine days later she complained of abdominal pain, nausea,
      vomiting, fever of 40 degrees C and chest discomfort. A serum total
      triiodothyronine of 575.2 nmol/l was measured by chemoluminiscent immunoassay
      eleven hours after the intake of the latest capsule (normal level: 1.1-2.9
      nmol/l). Along the following ten days the patient suffered from delirium,
      agitation, tachycardia, hypertension, constipation and later diarrhoea, but
      neither arrythmias nor axillary temperature over 38 degrees C. Fifty-nine
      measurements of the serum total triiodothyronine were performed in order to
      determine the kinetics of elimination of this drug. We estimate that the maximal
      serum concentration after the intake of the latest capsule could be 794.3 nmol/l,
      i.e. 397 times higher than the mean normal value. The elimination half-life was
      24 hours 40 minutes. The charcoal haemoperfusion had no impact on the velocity of
      elimination. The concentration of triiodothyronine became normal 200 hours after
      the intake of the latest capsule, but the clinical manifestations still lasted
      three days more. The pharmacokinetic data suggest that this intoxication could be
      due to the intake of capsules containing 5 mg of triiodothyronine, i.e. a dose
      200 times higher than that prescribed by her physician.

PMID- 14697085
TI  - [Septicemia caused by Vibrio cholerae non-01 in immunocompromised patient].
AB  - We describe the remarkable case of a patient with septicemia caused by Non 0-1
      Vibrio Cholerae associated with skin lesion of the lower and upper extremities.
      This patient suffered from chronic liver disease and a cervix carcinoma in IIIB
      stage, she had been admitted to the hospital the day before for dicompensated
      ascites. She received intravenous cefotaxime and had a satisfactory recovery and
      was completely free of signs and symptoms. We report its epidemiological
      discovery in inland freshwater and this is the first announced case in Spain with
      this confirmed environmental isolation and a rare report case in the literature.

PMID- 14697086
TI  - [Inclusion of health-related quality of life studies alongside clinical trials:
      basis and practical recommendations. Utilization of a check-list for their
      correct desing and evaluation].

PMID- 14697087
TI  - [Terminal sedation. Ethic aspects].
AB  - For better or for worse, bioethics is a discipline that, on occasion, presents
      more doubts and questions than solutions or answers for the variety of issues it
      implies. Sedation-as it concerns the terminally ill patient-is a clear example of
      one such issue. Sedation, used to diminish the intense suffering of those
      terminally ill patients who do not respond to conventional treatment, is a
      standard method by which the practice of palliative care presents often
      significant bioethical conflicts. I reconsider these ethical dilemmas that occur
      as a result of this decision.

PMID- 14697088
TI  - [Acute dystonic reaction due to quinine].

PMID- 14697089
TI  - [Localized Castleman's disease in the cervical region].

PMID- 14697090
TI  - [A new case of eosinophilic gastroenteritis].

PMID- 14697091
TI  - [Spontaneous dissection of carotid arteries. A case report].

PMID- 14697092
TI  - [Corynebacterium macginleyi as an exceptional cause of endocarditis: a case
      report].

PMID- 14697093
TI  - [Duodenal diverticula periampullary: new entity in the differential diagnosis of
      pancreatic abscess].

PMID- 14697094
TI  - [Enlargement of QT-interval in a patient with coronary disease treated with
      mianserin].

PMID- 14697095
TI  - [Capnocytophaga bacteriemia and pulmonary embolism].

PMID- 14697096
TI  - [Acromegaly presenting with severe hyperhidrosis].

PMID- 14697097
TI  - The Granzyme B ELISPOT assay: an alternative to the 51Cr-release assay for
      monitoring cell-mediated cytotoxicity.
AB  - BACKGROUND: The interferon-gamma (IFN-gamma) ELISPOT assay is one of the most
      useful techniques for immunological monitoring of cancer vaccine trials and has
      gained increased application as a measure of specific T cell activation. However,
      it does not assess cell-mediated cytotoxicity directly as IFN-gamma secretion is
      not limited to only cytolytic cells. Granzyme B (GrB) is a key mediator of target
      cell death via the granule-mediated pathway. Therefore, the release of GrB by
      cytolytic lymphocytes upon effector-target interaction may be a more specific
      indicator of CTL and NK cytotoxic ability than IFN-gamma secretion. METHODS: We
      assessed whether the GrB ELISPOT assay is a viable alternative to the 51Cr
      release and IFN-gamma ELISPOT assays for measuring antigen-specific CTL
      cytotoxicity. Direct comparisons between the three assays were made using human
      CTL cell lines (alphaEN-EBV and alphaJY) and an in vitro stimulated anti-Flu
      matrix peptide (FMP)-specific CTL. RESULTS: When the GrB ELISPOT was directly
      compared to the IFN-gamma ELISPOT and 51Cr-release assays, excellent cross
      correlation between all three assays was shown. However, measurable IFN-gamma
      secretion in the ELISPOT assay was observed only after 1 hour of incubation and
      cytotoxicity assessed via the 51Cr-release assay after 4 hours, whereas GrB
      secretion was detectable within 10 min of effector-target contact with
      significant secretion observed after 1 h. Titration studies demonstrated a strong
      correlation between the number of effector cells and GrB spots per well.
      Irrelevant targets or antigens did not induce significant GrB secretion.
      Additionally, GrB secretion was abrogated when CTL cultures were depleted of CD8+
      cells. CONCLUSION: Our findings demonstrate that the GrB ELISPOT assay is a
      superior alternative to the 51Cr-release assay since it is significantly more
      sensitive and provides an estimation of cytotoxic effector cell frequency.
      Additionally, unlike the IFN-gamma ELISPOT assay, the GrB ELISPOT directly
      measures the release of a cytotolytic protein. Detection of low frequency tumor
      specific CTL and their specific effector functions can provide valuable insight
      with regards to immunological responses.

PMID- 14697098
TI  - Heterogeneity within the Asian American community.
AB  - BACKGROUND: Educational interventions are grounded on scientific data and
      assumptions about the community to be served. While the Pan Asian community is
      composed of multiple, ethnic subgroups, it is often treated as a single group for
      which one health promotion program will be applicable for all of its cultural
      subgroups. Compounding this stereotypical view of the Pan Asian community, there
      is sparse data about the cultural subgroups' similarities and dissimilarities.
      The Asian Grocery Store based cancer education program evaluation data provided
      an opportunity to compare data collected under identical circumstances from
      members of six Asian American cultural groups. METHODS: A convenience sample of
      1,202 Asian American women evaluated the cultural alignment of a cancer education
      program, completing baseline and follow-up surveys that included questions about
      their breast cancer knowledge, attitudes, and screening behaviors. Participants
      took part in a brief education program that facilitated adherence to recommended
      screening guidelines. RESULTS: Unique recruitment methods were needed to attract
      participants from each ethnic group. Impressions gained from the aggregate data
      revealed different insights than the disaggregate data. Statistically significant
      variations existed among the subgroups' breast cancer knowledge, attitudes, and
      screening behaviors that could contribute to health disparities among the
      subgroups and within the aggregate Pan Asian community. CONCLUSION: Health
      promotion efforts of providers, educators, and policy makers can be enhanced if
      cultural differences are identified and taken into account when developing
      strategies to reduce health disparities and promote health equity.

PMID- 14697099
TI  - Uses of population census data for monitoring geographical imbalance in the
      health workforce: snapshots from three developing countries.
AB  - BACKGROUND: Imbalance in the distribution of human resources for health (HRH),
      eventually leading to inequities in health services delivery and population
      health outcomes, is an issue of social and political concern in many countries.
      However, the empirical evidence to support decision-making is often fragmented,
      and many standard data sources that can potentially produce statistics relevant
      to the issue remain underused, especially in developing countries. This study
      investigated the uses of demographic census data for monitoring geographical
      imbalance in the health workforce for three developing countries, as a basis for
      formulation of evidence-based health policy options. METHODS: Population-based
      indicators of geographical variations among HRH were extracted from census
      microdata samples for Kenya, Mexico and Viet Nam. Health workforce statistics
      were matched against international standards of occupational classification to
      control for cross-national comparability. Summary measures of inequality were
      calculated to monitor the distribution of health workers across spatial units and
      by occupational group. RESULTS: Strong inequalities were found in the
      geographical distribution of the health workforce in all three countries, with
      the highest densities of HRH tending to be found in the capital areas. Cross
      national differences were found in the magnitude of distributional inequality
      according to occupational group, with health professionals most susceptible to
      inequitable distribution in Kenya and Viet Nam but less so in Mexico compared to
      their associate professional counterparts. Some discrepancies were suggested
      between mappings of occupational information from the raw data with the
      international system, especially for nursing and midwifery specializations.
      CONCLUSIONS: The problem of geographical imbalance among HRH across countries in
      the developing world holds important implications at the local, national and
      international levels, in terms of constraints for the effective deployment,
      management and retention of HRH, and ultimately for the equitable delivery of
      health services. A number of advantages were revealed of using census data in
      health research, notably the potential for producing detailed statistics on
      health workforce characteristics at the sub-national level. However, lack of
      consistency in the compilation and processing of occupational information over
      time and across countries continues to hamper comparative analyses for HRH policy
      monitoring and evaluation.

PMID- 14697100
TI  - Bilateral asynchronous acute epidural hematoma : a case report.
AB  - BACKGROUND: Bilateral extradural hematomas have only rarely been reported in the
      literature. Even rarer are cases where the hematomas develop sequentially, one
      after removal of the other. Among 187 cases of operated epidural hematomas during
      past 4 years in our hospital, we found one case of sequentially developed
      bilateral epidural hematoma. CASE PRESENTATION: An 18-year-old conscious male
      worker was admitted to our hospital after a fall. After deterioration of his
      consciousness, an emergency brain CT scan showed a right temporoparietal epidural
      hematoma. The hematoma was evacuated, but the patient did not improve afterwards.
      Another CT scan showed contralateral epidural hematoma and the patient was
      reoperated. Postoperatively, the patient recovered completely. CONCLUSIONS: This
      case underlines the need for monitoring after an operation for an epidural
      hematoma and the need for repeat brain CT scans if the patient does not recover
      quickly after removal of the hematoma, especially if the first CT scan has been
      done less than 6 hours after the trauma. Intraoperative brain swelling can be
      considered as a clue for the development of contralateral hematoma.

PMID- 14697101
TI  - Severity of injury and mortality associated with pediatric blunt injuries:
      hospitals with pediatric intensive care units versus other hospitals.
AB  - OBJECTIVE: To a) compare in-hospital mortality rates for pediatric (age <13 yrs)
      patients with blunt injuries in the New York State Trauma Registry based on
      hospital type (dedicated pediatric intensive care unit [PICU] and designated
      trauma centers and noncenters that do not have a dedicated PICU) for the purpose
      of determining whether there is a reduction in mortality at a specialty hospital
      and b) determine the extent to which high-risk patients are admitted to specialty
      hospitals. DATA SOURCE: Inpatient data for the years 1994-1998 in the New York
      State Trauma Registry. STUDY SELECTION: A total of 8,180 pediatric inpatients who
      suffered blunt injury were selected to examine where patients were treated (PICU,
      regional trauma center without PICU, area trauma center without PICU, or
      noncenter without PICU) as a function of injury severity. DATA EXTRACTION: Data
      were extracted for inpatients aged <13 yrs who suffered blunt injury. DATA
      SYNTHESIS: The injury severity of inpatients treated at PICUs and regional
      centers without PICUs was significantly higher than at other hospitals. Risk
      factors that were independently related to survival of pediatric trauma
      inpatients were age <5 yrs, motor component of one to five, abnormal systolic
      blood pressure relative to age, and International Classification of Disease,
      Ninth Revision-Based Injury Severity Score. Of the total 136 deaths, 133 were
      among the patients <5 yrs old, motor score <6, and age-related abnormal systolic
      blood pressure. A total of 66.8% of these patients were treated at PICUs, and
      9.9% were treated at regional centers without PICUs. No statistically significant
      differences in risk-adjusted mortality rates were found by hospital type, but
      rates at PICUs were lower than for other types of hospitals except for noncenters
      without PICUs, whose patients were considerably less severely injured.
      CONCLUSIONS: There is significant triaging of the most seriously injured
      pediatric trauma inpatients to PICUs, and there is evidence that this policy is
      effective.

PMID- 14697102
TI  - Adenosine infusion for the management of persistent pulmonary hypertension of the
      newborn.
AB  - OBJECTIVE: To determine the effect of adenosine for the management of persistent
      pulmonary hypertension of the newborn. DESIGN: Prospective, observational case
      series report. SETTING: A single, tertiary referral neonatal intensive care unit.
      PATIENTS: Nine neonates with persistent pulmonary hypertension of the newborn
      requiring mechanical ventilation and inhaled nitric oxide at 20 parts per
      million. INTERVENTIONS: A continuous intravenous infusion of adenosine at 50
      microg/kg/min. MEASUREMENTS AND MAIN RESULTS: Peripheral arterial oxygen
      saturation, arterial oxygen tension, invasive systemic arterial blood pressure,
      and pulmonary arterial pressure, estimated using echocardiography, were recorded.
      There was a significant improvement in arterial oxygenation tension in six of
      nine neonates who responded to adenosine: PaO2 increased from 66.8 (range, 47
      70.5) torr (8.8 kPa) to 73.5 (range, 58.5-94.2) (p=.02) and pulmonary arterial
      pressure decreased significantly from 63 (range, 42.5-64.0) to 43.5 (range, 32.75
      49) mm Hg (p=.002). The pulmonary to systemic mean artery pressure ratio fell
      from 1.27 (range, 0.88-1.5) to 0.81 (range, 0.64-0.84) (p=.002). Three neonates
      did not respond to adenosine infusion. CONCLUSIONS: The use of adenosine infusion
      in combination with inhaled nitric oxide may be a potentially valuable
      therapeutic option for the treatment of pulmonary hypertension of the newborn.
      Neonates with irreversible lung pathology may not respond to adenosine infusion.

PMID- 14697103
TI  - Low inferior vena caval catheters for hemodynamic and pulmonary function
      monitoring in pediatric critical care patients.
AB  - OBJECTIVE: To assess the value of low inferior vena caval (LIVC) catheters for
      estimating central venous pressure in pediatric intensive care patients and to
      assess influences of intra-abdominal pressures and mean airway pressure on these
      measurements. DESIGN: Prospective cohort of consecutive patients. SETTING:
      Pediatric intensive care unit. PATIENTS: Thirty patients ranging in age (18, 0-1
      yrs; four, 1-3 yrs; four, 3-10 yrs; four, > or =10 yrs). INTERVENTIONS:
      Interventions included catheterizations via internal jugular, subclavian, and
      common femoral veins, as well as direct right atrial catheterization during
      surgery; arterial catheter placement; airway pressure monitoring during
      mechanical ventilation; indirect intra-abdominal pressure monitoring via bladder
      catheter pressure readings; and arterial and central venous blood gas analysis.
      LIVC vein catheters were placed below the origin of the renal veins. MEASUREMENTS
      AND MAIN RESULTS: LIVC pressure was highly correlated with central venous
      pressure (n=30, r2=.965, p=.0001). LIVC pressure did not correlate with intra
      abdominal pressure (n=18, r2=.000). Mean airway pressure did not correlate with
      central venous pressure (n=11, r2=.106). The pH of LIVC blood was similar to that
      of central venous blood (n=18, r2=.941, p=.0001). PCO2 values of inferior vena
      cava and central venous blood correlated (r2=.945, p=.0001). However, agreement
      between inferior vena cava and central venous PO2 and oxyhemoglobin saturation
      was poor (PO2, r2=.066; oxyhemoglobin saturation, r2=.000). CONCLUSIONS: LIVC
      catheters whose tips lie below the origin of the renal veins predict central
      venous pressure in pediatric intensive care unit patients. Intra-abdominal
      pressure and mean airway pressure do not affect this relationship, within the
      wide range of values for these variables included in this study. Blood samples
      drawn from femoral venous catheters can be used to monitor acid-base balance and
      partial pressure of carbon dioxide.

PMID- 14697104
TI  - Predicted versus measured energy expenditure by continuous, online indirect
      calorimetry in ventilated, critically ill children during the early postinjury
      period.
AB  - OBJECTIVE: Compare the energy expenditure, predicted by anthropometric equations,
      with that measured by continuous on-line indirect calorimetry in ventilated,
      critically ill children during the early postinjury period. DESIGN: Prospective,
      clinical study. SETTING: Pediatric intensive care unit of a pediatric university
      hospital. PATIENTS: A total of 43 ventilated, critically ill children during the
      first 6 hrs after injury. INTERVENTIONS: An indirect calorimeter was used to
      continuously measure the energy expenditure for 24 hrs. MEASUREMENTS AND MAIN
      RESULTS: Clinical data collected were age, gender, actual and ideal weight,
      height, and body surface. Nutritional status was assessed by Waterlow and Shukla
      Index. Severity of illness was determined by Pediatric Risk of Mortality,
      Physiologic Stability Index, and Therapeutic Intervention Scoring System. Energy
      expenditure was measured (MEE) by continuous on-line indirect calorimetry for 24
      hrs. Predicted Energy Expenditure (PEE) was calculated using the Harris-Benedict,
      Caldwell-Kennedy, Schofield, Food and Agriculture/World Health
      Organization/United Nation Union, Maffeis, Fleisch, Kleiber, Dreyer, and Hunter
      equations, using the actual and ideal weight. MEE and PEE were compared using
      paired Student's t-test, linear correlation (r), intraclass correlation
      coefficient (pI), and the Bland-Altman method. Mean MEE resulted in 674 +/- 384
      kcal/day. Most of the predictive equations overestimated MEE in ventilated,
      critically ill children during the early postinjury period. MEE and PEE differed
      significantly (p<.05) except when the Caldwell-Kennedy and the Fleisch equations
      were used. r2 ranged from 0.78 to 0.81 (p<.05), and pI was excellent (>.75) for
      the Caldwell-Kennedy, Schofield, Food and Agriculture/World Health
      Organization/United Nation Union, Fleisch, and Kleiber equations. The Bland
      Altman method showed poor accuracy; the Caldwell-Kennedy equation was the best
      predictor of energy expenditure (bias, 38 kcal/day; precision, +/- 179 kcal/day).
      The accuracy in the medical group was higher (pI range,.71-.94) than in surgical
      patients (pI range,.18-.75). CONCLUSIONS: Predictive equations do not accurately
      predict energy expenditure in ventilated, critically ill children during the
      early postinjury period; if available, indirect calorimetry must be performed.

PMID- 14697105
TI  - Glucocorticoids reduce cardiac dysfunction after cardiopulmonary bypass and
      circulatory arrest in neonatal piglets.
AB  - OBJECTIVE: The hypotheses were that glucocorticoid administration could improve
      ventricular recovery by reducing cardiopulmonary bypass (CPB)-induced
      inflammatory response and that presurgical administration might be more effective
      than intraoperative dosing. DESIGN: Animal case study. SUBJECTS: Crossbred
      piglets (5-7 kg). INTERVENTIONS: Piglets were cooled with CPB, followed by 120
      mins of deep hypothermic circulatory arrest (DHCA). Animals were rewarmed to 38
      degrees C, removed from CPB, and maintained for 120 mins. Methylprednisolone (60
      mg/kg) was administered in the CPB pump prime (intraoperative glucocorticoid
      [intraop GC]) or 6 hrs before CPB (30 mg/kg) in addition to the intraoperative
      dose (30 mg/kg; pre- and intraop GC). Controls (no GC) received saline.
      MEASUREMENTS AND MAIN RESULTS: In no GC, left ventricle (LV) positive change in
      pressure in time (+dP/dt) (mm Hg/sec) had a mean +/- SD of 1555 +/- 194 at
      baseline vs. 958 +/- 463 at 120 mins after CPB, p=.01). LV +dP/dt was maintained
      in glucocorticoid-treated animals (1262 +/- 229 at baseline vs. 1212 +/- 386 in
      intraop GC and 1471 +/- 118 vs. 1393 +/- 374 in pre-intraop GC). Glucocorticoids
      reduced myocardial interleukin-6 messenger RNA expression, measured by
      ribonuclease protection assay, at 120 mins after CPB compared with animals
      receiving saline (p<.05), although interleukin-6 plasma and LV protein
      concentrations were not affected. Interleukin-10 myocardial protein
      concentrations were elevated after CPB-DHCA with higher concentrations in
      glucocorticoid-treated animals (p<.05). Glucocorticoid treatment maintained
      myocardial concentrations of the inhibitor of nuclear factor-kappaB in the
      cytosol and decreased nuclear factor-kappaB concentrations detected in the
      nucleus in a DNA/protein interaction array. CONCLUSIONS: Glucocorticoids improved
      recovery of LV systolic function in neonatal animals undergoing CPB-DHCA. Animals
      receiving glucocorticoids before CPB had better postoperative oxygen delivery
      than those receiving only intraoperative treatment. Maintenance of cardiac
      function after glucocorticoids might be due, in part, to alterations in the
      balance of pro- and anti-inflammatory proteins, possibly through nuclear factor
      kappaB-dependent pathways.

PMID- 14697106
TI  - Use of the nursing acuity score in children admitted to a pediatric oncology
      intensive care unit.
AB  - OBJECTIVE: To determine whether a unit specific nursing acuity score is useful
      for assessing patients with cancer admitted to the pediatric intensive care unit.
      DESIGN: Prospective, cohort analysis. SETTING: The intensive care unit of a
      tertiary-care pediatric oncology hospital. PATIENTS: A total of 219 patients
      admitted to the pediatric intensive care unit with a diagnosis of cancer or after
      hematopoietic stem cell transplantation. INTERVENTIONS: The nursing acuity scores
      obtained during the second shift after admission were recorded and compared with
      rates of mortality. These nursing acuity scores were also compared with the
      Pediatric Risk of Mortality (PRISM III) and Therapeutic Intervention Scoring
      System (TISS-28) scores recorded during the first day of intensive care unit
      admission. MAIN RESULTS: Mortality differed across the nursing acuity categories
      (0%, 7.5%, 20.8%, and 47.4%; p=.0002). TISS-28 and PRISM III scores progressively
      increased with each increase in the categorical nursing score and differed
      significantly among these levels (TISS-28, p=.0078; PRISM III, p=.0327). The
      Spearman correlation coefficients between the nursing score and TISS-28 and PRISM
      III were 0.432 and 0.285, respectively (p<.0001). CONCLUSIONS: The nursing acuity
      score accurately predicts survival in pediatric patients with cancer, correlates
      with established indexes of severity of illness and predictors of mortality, and
      identifies different mortalities across the nursing acuity categories. Although
      its predictive value may have been enhanced by the use of a second shift score,
      these findings suggest that it may be a useful tool in this patient population
      and affirms the insight of the bedside nurse in assessing severity of illness.

PMID- 14697107
TI  - Decision making and satisfaction with care in the pediatric intensive care unit:
      findings from a controlled clinical trial.
AB  - OBJECTIVE: To facilitate critical decision making and improve satisfaction with
      care among families of patients in a pediatric intensive care unit. DESIGN:
      Prospective observational study followed by a nonrandomized controlled trial of a
      clinical intervention to identify conflicts and facilitate communication between
      families and the clinical team. SETTING: The pediatric intensive care unit of a
      Boston teaching hospital. PATIENTS: A total of 127 patients receiving care in the
      pediatric intensive care unit in 1998-1999 and their families. INTERVENTIONS:
      Interviews were conducted with surrogates and decisionally capable older children
      concerning the adequacy of information provided, understanding, communication,
      and perceived decisional conflicts. Findings were relayed to the clinical team,
      who then developed tailored follow-up recommendations. MEASUREMENTS AND MAIN
      RESULTS: A survey administered to surrogates at baseline and day 7 or intensive
      care unit discharge measured satisfaction with care. Information on patient
      acuity and hospital stay were extracted from medical records and hospital
      databases. Wilcoxon rank-sum tests and incidence rate comparisons were used to
      assess the impact of the intervention on satisfaction and sentinel decision
      making, respectively. Incidence rates of care plan decision making, including
      decisions to adopt a comfort-care-only plan and decisions to forego
      resuscitation, were lower among families who received the intervention. The
      intervention did not significantly affect satisfaction with care. CONCLUSIONS:
      Prospectively screening for and intervening to mitigate potential conflict did
      not increase decision making or parental satisfaction with the care provided in
      this pediatric intensive care unit.

PMID- 14697108
TI  - Exhaled nitric oxide reflects asthma severity and asthma control.
AB  - INTRODUCTION: This study was undertaken to a) evaluate whether exhaled nitric
      oxide (fraction of exhaled nitric oxide [FENO]) levels are reflective of asthma
      severity in concordance with the National Asthma Education and Prevention Program
      categorization and b) determine the usefulness of FENO using the single-breath
      exhalation technique for monitoring asthma control and compliance with steroid
      treatment. METHODS: Thirty patients with asthma (7-17 yrs old; 14 males and 16
      females) that was mild (n=8), moderate (n=17), or severe (n=5) were included in
      the study. Fifteen patients were seen on more than one occasion for a total of 53
      visits. Information obtained at each visit included asthma symptoms, beta
      agonists and corticosteroids use, compliance to steroids, and forced expiratory
      volume in 1 sec (FEV1) and FENO measurements. Asthma control was judged by a
      pulmonologist based on overall evaluation of symptoms, FEV1 measurements, and the
      frequency of beta-agonists use at each visit. RESULTS: The mean +/- SD FENO was
      significantly different in the mild, moderate, and severe asthma categories (30
      +/- 12, 65 +/- 48, 104 +/- 68, respectively; F(2,52)=6.02 p=.005). FENO was
      significantly correlated with asthma severity (r=.44, p=.001), compliance (r=
      .75, p=.001), and control (r=-.51, p=.001). There were no statistically
      significant differences between asthma severity and compliance or FEV1.
      DISCUSSION: Our data suggest that a) FENO may be a practical tool to evaluate
      asthma severity and asthma control over time and b) FENO may be used as a marker
      of compliance with steroids even when FEV1 has not decreased significantly.

PMID- 14697109
TI  - Cerebrospinal fluid levels of S-100beta in children and its elevation in
      pediatric meningitis.
AB  - OBJECTIVE: To describe normal cerebrospinal fluid (CSF) levels of S-100beta in
      children and determine whether CSF S-100beta levels are elevated in pediatric
      meningitis. DESIGN: Cohort study. SETTING: Children's teaching hospital.
      PATIENTS: A total of 141 children (107 controls and 34 meningitis patients).
      METHODS: CSF levels of S-100beta were measured in 107 control patients and 34
      children with meningitis. S-100beta levels were measured in CSF collected from a
      lumbar puncture to evaluate for meningitis. Patients were classified as controls
      if they did not have pleocytosis or an organism identified. Patients were
      classified as having meningitis if there was CSF pleocytosis. Those with
      meningitis were then categorized as having bacterial or aseptic meningitis. S
      100beta levels were measured by a commercial luminometric assay. Data are
      presented as median (interquartile range [IQ]) unless otherwise noted.
      MEASUREMENTS AND MAIN RESULTS: Normal CSF S-100beta levels were measured in 107
      children with a median age of 2.6 months (1.4 months to 1.5 yrs). The median CSF
      S-100beta was 0.71 microg/L (IQ range, 0.48-1.07) with a tenth to 90th percentile
      range of 0.35-1.8 microg/L. A correlation was measured between age and CSF S
      100beta levels in controls, (r2=.04, p=.037). Thirty-four children had meningitis
      with a median age of 4.0 yrs (2.0 months to 11.8 yrs). Ten were
      bacterial/mycobacterial, and 24 were aseptic. Children with meningitis had
      elevated S-100beta levels of 1.1 microg/L (IQ range, 0.9-1.6) compared with
      control levels of 0.71 microg/L (IQ range, 0.48-1.07) (p=.0001). Those with
      bacterial/mycobacterial meningitis had elevated S-100beta levels of 1.6 microg/L
      (IQ range, 0.78-3.0) compared with controls (p=.002). Children with aseptic
      meningitis also had S-100beta levels of 1.0 microg/L (IQ range, 0.91-1.4), which
      were elevated compared with controls, (p=.0003). CONCLUSIONS: CSF levels of S
      100beta are elevated in children with meningitis compared with controls.

PMID- 14697110
TI  - Decreasing unplanned extubations: utilization of the Penn State Children's
      Hospital Sedation Algorithm.
AB  - OBJECTIVE: To determine whether institution of a standardized algorithm of goal
      directed sedation impacted the incidence of unplanned extubations in critically
      ill pediatric patients. DESIGN: Prospective, observational study with historical
      controls. SETTING: Pediatric intensive care unit (PICU) in a tertiary care
      university-based children's hospital. PATIENTS: All mechanically ventilated
      children admitted to the PICU during a 10-yr period. INTERVENTIONS: After
      examining the data pertaining to unplanned extubations, the Penn State Children's
      Hospital Sedation Algorithm (PSCHSA) was instituted as an absolute requirement
      for all mechanically ventilated children. Physician orders for the goal sedation
      level and the appropriate medications to achieve that goal were obligatory for
      every ventilated patient. Data were then collected for 5 yrs after institution of
      the PSCHSA. MEASUREMENTS AND MAIN RESULTS: Before utilization of the PSCHSA,
      unplanned extubation rates ranged between 0.44 and 0.63 per 100 intubated patient
      days. In the 4 yrs after mandatory use of the PSCHSA for management of all
      ventilated patients, unplanned extubation rates were between 0 and 0.19 per 100
      intubated patient days, demonstrating a significant decrease (p<.001). Throughout
      the entire study period, no changes were made in the model of patient care that
      would alter the rate of unplanned extubations. Despite a higher percentage of
      PICU patients that were intubated, length of stay in the PICU did not increase,
      suggesting that oversedation did not led to increased ventilator days.
      CONCLUSIONS: Utilization of the PSCHSA resulted in a decreased number of
      unplanned extubations without increasing the length of PICU stay. Implementation
      of the PSCHSA is needed in other PICUs to validate these findings.

PMID- 14697111
TI  - Factors associated with early extubation after cardiac surgery in young children.
AB  - OBJECTIVE: Children undergoing congenital heart surgery require mechanical
      ventilation. We sought to identify pre- and intraoperative factors (PrO, IO)
      associated with successful early extubation <24 hrs. DESIGN AND PATIENTS: We
      performed a retrospective chart review of children <36 months old who underwent
      congenital heart surgery from January 1998 to July 1999. SETTING: Pediatric
      intensive care unit in a children's hospital. MEASUREMENTS: Generalized
      Estimating Equation models were fit to assess the association between PrO and IO
      and early extubation while accounting for the correlation between surgeries
      performed on the same patient. Estimated odds ratios (EOR) and 95% confidence
      intervals were calculated. Multivariable models were constructed using a forward
      selection process with inclusion criteria of p<.05. Multivariable models, which
      included PrO and IO variables, were adjusted for procedure group. The area under
      the receiver operating characteristic curve was computed for each model. RESULTS:
      A total of 203 children underwent 219 surgeries; 103 (47%) children were
      extubated in <24 hrs, with only one (1%) failed extubation. PrO variables
      associated with successful early extubation included age >6 months (EOR, 6.1),
      absence of pulmonary hypertension (EOR, 9.1), gestational age >36 wks (EOR, 4.6),
      and absence of congestive heart failure (EOR, 2.4). IO variables were less likely
      to be associated with successful early extubation. Our model of PrO variables
      with multiple factors showed that presence of two factors was associated with an
      EOR of 4.2 for successful early extubation compared with children with zero or
      one factor. Presence of three and four factors was associated with an EOR of 18.0
      and 76.5, respectively. The area under the receiver operating characteristic
      curve for this model is 0.816. Incision type, complex vs. simple procedure, and
      palliative vs. complete repair were not associated with success of early
      extubation. CONCLUSIONS: Early extubation is possible in many very young children
      undergoing congenital heart surgery, with a low rate of failed extubation. The
      model would be improved by prospective validation with larger numbers at multiple
      institutions.

PMID- 14697112
TI  - Feasibility of red blood cell transfusion through small bore central venous
      catheters used in neonates.
AB  - OBJECTIVE: To determine whether packed red blood cell transfusions through small
      bore central venous catheters used in critically ill neonates results in
      significant hemolysis. DESIGN: In vitro experimental study using a mock
      transfusion setup incorporating a syringe pump, prestorage leukoreduced fresher,
      and older CPDA-1 red blood cell units and pressure transducer simulating neonatal
      transfusion through 1.9-Fr NeoPICC central venous catheter. SETTING: Laboratory
      setting. SUBJECTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Spun
      hematocrit, plasma free hemoglobin (hemoglobin), lactate dehydrogenase, and
      potassium were analyzed pretransfusion, at various times during transfusion, and
      posttransfusion. Intraluminal pressures were measured using a TruWave Disposable
      Pressure Transducer. Using fresher (5-8 days old) and older (29-30 days old) CPDA
      1 red blood cells, we compared 2 and 20 mL/hr flow rates. Statistical analysis
      was performed using repeated measures of analysis of variance to compare the
      differences in means between flow rates. Mean intraluminal pressures at the end
      of each experiment were significantly higher at 20 mL/hr flow rates (>360 mm Hg)
      in both fresher and older red blood cells than at 2 mL/hr (range, 61-70 mm Hg).
      Overall, potassium, lactate dehydrogenase, and plasma free hemoglobin
      concentrations were significantly higher for older red blood cells at either 2 or
      20 mL/hr (p<.001). Both fresher and older red blood cells demonstrated higher
      potassium concentrations at 20 mL/hr (22.4%, p<.001;0.7%, p>.05, respectively);
      however, these increases were not clinically significant. Furthermore, lactate
      dehydrogenase, hematocrit, and plasma free hemoglobin differences seen at 2 and
      20 mL/hr did not coincide with changes in potassium. CONCLUSIONS: No clinically
      significant hemolysis was evidenced with red blood cell transfusion through small
      bore central venous catheters when using fresher or older CPDA-1 red blood cells
      at 2 or 20 mL/hr.

PMID- 14697113
TI  - Current limitations of volumetric capnography in surfactant-depleted small lungs.
AB  - OBJECTIVE: To investigate the suitability of volumetric capnography for assessing
      alveolar gas exchange in very small, surfactant-depleted lungs. DESIGN:
      Prospective animal trial. SETTINGS: Animal laboratory in a university setting.
      SUBJECTS: Twenty-one ventilated newborn piglets (age <12 hrs; median weight, 890
      g; range, 560-1435 g). INTERVENTIONS: Bronchoalveolar lavage with instillation of
      30 mL/kg normal saline. Ventilatory, circulatory, and lung mechanic variables
      were measured before and 0, 30, and 60 mins after bronchoalveolar lavage.
      MEASUREMENTS AND MAIN RESULTS: The alveolar deadspace fraction calculated by the
      Bohr and the Bohr/Enghoff equations increased three-fold (p<.001) after
      bronchoalveolar lavage in capnograms with distinct alveolar plateau, whereas in
      capnograms without alveolar plateau no statistical significant difference was
      seen. The main problem of capnography in small and especially stiff lungs was the
      high number of discarded records exclusively caused by a missing alveolar
      plateau. Rates of discarded records of capnography were 9.5% before lavage and
      increased (p<.01) to 52.4%, 47.6%,42.8% after bronchoalveolar lavage (0, 30, and
      60 mins). With decreasing exhalation time, the number of discarded records
      increased significantly. No plateau was seen in >75% of recorded files with
      exhalation times <200 msecs. The effect of bronchoalveolar lavage on all
      variables measured was quite different, with the highest impact on required
      ventilatory settings, calculated oxygenation variables, and compliance. The
      effect of bronchoalveolar lavage on arterio-alveolar CO2 difference, CO2
      production, and alveolar deadspace was much lower and statistically significant
      only in capnograms with alveolar plateau. CONCLUSIONS: Volumetric capnography is
      a useful tool to detect impaired alveolar gas exchange in surfactant-depleted
      small lungs. However, the method failed if there was no alveolar plateau in the
      volumetric capnogram especially in stiff lungs with short exhalation times.

PMID- 14697114
TI  - Hypokalemia in children with severe falciparum malaria.
AB  - OBJECTIVES: Acidosis is now recognized as an important component of the severe
      malaria syndrome and a predictor of fatal outcome. Alterations in plasma
      potassium concentrations are commonly associated with acidosis. To date, there is
      little information about the changes in potassium in severe malaria. DESIGN:
      Prospective study examining the changes in plasma potassium in the first 24 hrs
      following admission in children with severe malaria. Urinary fractional excretion
      of potassium and the transtubular gradient of potassium were examined at
      admission. SETTING: High-dependency unit on the coast of Kenya. PATIENTS: Kenyan
      children admitted to hospital with clinical features of severe malaria (impaired
      consciousness or deep breathing) complicated by acidosis (base deficit >8).
      INTERVENTIONS: Children received standard therapy for severe malaria; in
      addition, they received boluses of either 0.9% saline or 4.5% human albumin
      solution to correct hypovolemia, and intravenous potassium replacement was
      prescribed to children who developed hypokalemia (plasma potassium <3 mmol/L).
      MEASUREMENTS AND MAIN RESULTS: Thirty-eight Kenyan children were recruited with
      severe malaria and acidosis. At admission, serum potassium was normal (3-5.5
      mmol/L) in 31 (81.6%) and low (<3 mmol/L) in four (11%) children, and three
      (6.3%) children had hyperkalemia (>5.5 mmol/L). Plasma potassium decreased
      rapidly within 4-8 hrs of admission: 15 (40%) patients were hypokalemic (<3
      mmol/L); of these, five (13%) had plasma potassium of <2.5 mmol/L. Fractional
      excretion of potassium and the transtubular gradient of potassium were above
      normal range, indicating renal potassium loss. CONCLUSIONS: Hypokalemia is a
      common complication of severe malaria; however, it is often not apparent on
      admission. On correction of acidosis, plasma potassium decreases precipitously,
      and thus careful, serial monitoring of serum potassium is suggested in patients
      with severe malaria complicated by acidosis.

PMID- 14697115
TI  - Cavernous sinus thrombosis complicating sinusitis.
AB  - BACKGROUND: Septic cavernous sinus thrombosis is a rare complication of paranasal
      sinusitis. OBJECTIVE: To familiarize the clinician with the pathogenesis,
      diagnosis, and appropriate management of septic cavernous sinus thrombosis.
      DESIGN: Case report and literature review. SETTING: Pediatric intensive care unit
      in a university hospital. PATIENT: We present a 12-yr-old female with a 1 wk
      history of an upper respiratory tract infection with worsening dyspnea, cough,
      and swelling of the left eye progressing to adult respiratory distress syndrome.
      Secondary to the need for significant mechanical ventilatory support, venovenous
      extracorporeal membrane oxygenation was initiated. Computed tomography scan of
      the head and neck with contrast revealed bilateral cavernous sinus thrombosis.
      After broad-spectrum intravenous antibiotics and aggressive supportive care in
      conjunction with surgical intervention (maxillary sinus lavage and right orbital
      exploration) and anticoagulation therapy, the patient recovered. Blood cultures
      were positive for Viridans streptococcus. At discharge 3 wks later, the patient
      had improved, but had right-eye blindness. CONCLUSIONS: The diagnosis of septic
      cavernous sinus thrombosis requires a high index of suspicion and confirmation by
      imaging; early diagnosis and surgical drainage of the underlying primary source
      of infection in conjunction with long-term intravenous antibiotic therapy are
      critical for an optimal clinical outcome.

PMID- 14697116
TI  - Treatment of extreme hyperglycemia monitored with intracerebral microdialysis.
AB  - OBJECTIVE: Description of a pediatric patient with hyperosmolar hyperglycemic
      nonketotic syndrome where the treatment was monitored with intracerebral
      microdialysis. DESIGN: Case report. SETTING: Intensive care unit at a university
      hospital. PATIENT: An 11-yr-old boy with new-onset diabetes who presented with a
      blood glucose concentration of 100 mmol/L (1800 mg/dL) and a serum osmolality of
      448 mOsm/kg. INTERVENTIONS: Interventions included intracerebral and subcutaneous
      microdialysis as well as intracranial pressure monitoring during correction of
      the hyperosmolar condition. The strategy was to decrease osmolality by 1 mOsm.kg(
      1).hr(-1) and blood glucose by 1.5 mmol.L(-1).hr(-1) (27 mg/dL). MEASUREMENTS AND
      MAIN RESULTS: The concentrations of glucose in the subcutaneous dialysates
      corresponded to the blood glucose concentrations. The brain/subcutaneous glucose
      ratio varied between 0.20 and 1.28 (mean, 0.43; median, 0.4). When the blood
      glucose decreased quickly after steady state, the brain/subcutaneous ratio
      increased sharply, demonstrating that the normalization of glucose in the brain
      was slower than that in blood. CONCLUSIONS: Microdialysis can be used to monitor
      the brain/subcutaneous glucose ratio in patients with extreme hyperglycemia. A
      rapid decrease in blood glucose increases the brain/subcutaneous glucose ratio,
      which may be a potential risk factor for osmotic brain edema. Microdialysis may
      prove to be a valuable tool in treatment management. The child made a full
      recovery.

PMID- 14697117
TI  - Models of response to childhood sexual abuse: their implications for treatment.
AB  - Childhood sexual abuse (CSA) has been linked to adult mental health problems and
      indicators of severity of psychiatric illness. There exist large, unexplained
      individual differences in the presentation of mental health problems following
      CSA. Complex statistical methodologies allow researchers to examine models of
      response to CSA and its impact on mental health. Two early models are presented
      and critiqued. Two more recent models are then presented. It is concluded that
      whereas no single variable can, on its own, account for individual variation in
      symptom development, empirically tested models point toward a complex interaction
      between abuse-related factors, interactions with others (e.g., responses to
      disclosure, attachment), and individual factors (e.g., attributions, emotion
      focused coping) as mediators and moderators of outcome. The implications of
      increased understanding of the complex interaction of these factors in
      understanding clinical presentations and in the formulation of treatment plans
      are explored.

PMID- 14697118
TI  - Ask not for whom the bell tolls: controversy in post-traumatic stress disorder
      treatment outcome findings for war veterans.
AB  - This article reviews and analyzes two national studies of the efficacy of
      treatment for war veterans suffering from post-traumatic stress disorder (PTSD).
      A careful analysis of the studies conducted by the Department of Veterans Affairs
      (DVA) Northeast Program Evaluation Center (NEPEC) reveals conceptual,
      methodological, and design flaws in the research, which reports minimal treatment
      efficacy for PTSD. Based on this limited, if not biased, data, the results were
      used for policy purposes to dismantle inpatient PTSD hospital units and trauma
      focus treatments. A critique is offered as a review to suggest how future studies
      might be conducted, designed, and evaluated, including the need for independent,
      "outside" peer reviews inasmuch as the issue of treatment outcomes generalizes to
      many nonmilitary populations.

PMID- 14697119
TI  - Research and interventions to reduce domestic violence revictimization.
AB  - Despite decades of research on domestic violence, considerable challenges must be
      addressed to develop sound, theoretically and empirically based interventions for
      reducing domestic violence revictimization. Many basic and applied research
      issues remain unaddressed by existing studies, and evaluations frequently do not
      sufficiently highlight their limitations or program or policy implications.
      Nonetheless, progress has been made, and practitioners and policy makers
      increasingly have a wide range of promising interventions from which to select.
      This article reviews research on domestic violence and focuses particular
      attention on interventions aimed at reducing revictimization among individuals
      known to have been abused. It also provides a conceptual framework for
      practitioners and policy makers to situate existing evaluation research and
      highlights the need for better data to understand and assess efforts to reduce
      domestic violence revictimization. The author concludes by discussing directions
      for future research and recommendations for practice and policy.

PMID- 14697120
TI  - Stalking: knowns and unknowns.
AB  - The current work reviews literature on the nature of stalking. Despite its
      nebulous nature and differing legal and clinical definitions of stalking,
      researchers and practitioners are referring to the same phenomenon. Stalking is
      chronic, consisting of a number of nuisance behaviors that appear consistent over
      countries and samples. Different categorizations of stalkers and their victims
      exist, but ex-partner stalkers are a distinctive category with respect to their
      prevalence, violence risk, and attrition rate. Different samples and definitions
      and false victimization reports obscure reliable lifetime prevalence estimates,
      but these appear to be around 12%-16% among women and 4%-7% among men. Stalking
      has deleterious effects on victims but some of the effects may be the result of
      stalking's exacerbating of existing vulnerabilities. Future research should focus
      on subgroups of stalkers and their victims, on cross-cultural investigations, and
      on the co-occurrence of stalking with other crimes.

PMID- 14697121
TI  - Leaving an abusive partner: an empirical review of predictors, the process of
      leaving, and psychological well-being.
AB  - Four facets of leaving an abusive relationship are reviewed: (a). factors related
      to initially leaving an abusive partner; (b). the process of leaving an abusive
      relationship; (c). the psychological well-being of survivors after leaving; and
      (d). the predictors of this well-being. The conceptual and methodological
      limitations of studies in each of these areas are presented. Consistently found
      predictors of leaving include both material and psychological factors. Because
      battered women typically undergo several shifts in their thinking about the abuse
      before leaving permanently, research on leaving as a process is highlighted. A
      stress-process framework is used to explain the seemingly paradoxical finding
      that some women just out of the abusive relationship may have greater
      psychological difficulties than those who are still in it. For those experiencing
      the most stress, psychological health can worsen over time. Researchers and
      practitioners need to pay more attention to the plight of women who have left
      abusive partners.

PMID- 14697122
TI  - A review of the history of traumatic stress studies in Japan: from traumatic
      neurosis to PTSD.
AB  - Based on available literature, this review article investigates traumatic stress
      studies in Japan from the late 19th century to the present for English speaking
      audiences. First, traumatic neuroses of war victims, A-bomb survivors, and
      victims of work-related accidents are discussed. Second, traumatic stress studies
      of victims of other manmade disasters, such as the sarin gas attacks in Tokyo,
      domestic violence, and burn injuries. Third, psychological outcomes of natural
      disaster studies are discussed in relation to social support and help-seeking
      tendencies of Japan disaster victims.

PMID- 14697123
TI  - Community violence exposure in young adults.
AB  - The United States is one of the most violent countries in the world, and this is
      being reflected in rates of young adults' lifetime exposure ranging from 76% to
      82% for victimization and 93% to 96% for witnessing. These high rates are found
      despite these studies being conducted on relatively low-risk samples from rural
      areas, and the majority of violent acts reported being less life threatening than
      those reported by high-risk urban adolescents. Nonetheless, young adults with
      high levels of exposure report more psychological maladjustment including
      depressed mood, aggressive behavior, posttraumatic stress disorder
      symptomatology, and interpersonal problems. The cycle from exposure to later
      perpetration of aggression is discussed in terms of psychophysiological processes
      that may emerge from chronic violence exposure or interact with victimization to
      increase risk. Last, theoretical, clinical, and policy implications are suggested
      that include intervention and prevention programs targeting all forms of violence
      in urban and rural areas.

PMID- 14697124
TI  - Marital rape: history, research, and practice.
AB  - Despite the increased recognition that the topic of marital rape has generated in
      the past 2 decades, the literature in this area remains sparse. This article
      provides a comprehensive review of the current state of the marital rape
      literature. First, the lengthy history of legal, cultural, and professional
      invalidation of marital rape victims, and the resulting negative treatment
      implications, is discussed. Second, marital rape research is reviewed, including
      prevalence, descriptive, and comparison studies. This review highlights the
      seriousness of marital rape, in terms of prevalence and posttrauma distress, as
      well as the limitations of extant research. Finally, barriers to treatment and
      recommendations for professionals are discussed.

PMID- 14697125
TI  - Living in danger: the impact of chronic traumatization and the traumatic context
      on posttraumatic stress disorder.
AB  - In this article on the effects of chronic traumatization, research is reviewed
      regarding the association between chronicity of traumatization and posttraumatic
      stress disorder (PTSD) symptomatology. The contribution of the broader traumatic
      context to PTSD symptomatology is also examined. This review focuses on three
      populations: combat veterans, child sexual abuse survivors, and survivors of
      domestic violence. The challenges of defining chronicity of a traumatic event and
      traumatic context are addressed. Finally, suggestions for future directions are
      provided.

PMID- 14697126
TI  - Perpetrators of spousal homicide: a review.
AB  - It has been argued that individuals who engage in spouse abuse increase their
      violence toward their partners, which can culminate in the death of either the
      assaulter or the victim. The aim of this review is to identify risk factors that
      determine whether an abusive relationship will end in eventual death. An
      extensive search revealed 22 empirical research studies on risk factors for
      spousal homicide. The circumstances of spousal homicide are described and salient
      risk factors are highlighted. In the United Kingdom, 37% of all women were
      murdered by their current or former intimate partner compared to 6% of men. The
      most common cause of an intimate partner's death in England and Wales was being
      attacked with a sharp implement or being strangled. By contrast, the most common
      cause in the United States for spousal homicide was being shot. Nine major risk
      factors are found that may help predict the probability of a partner homicide and
      prevent future victims.

PMID- 14697127
TI  - [Assessment of non-surgery therapy for hepatocellular carcinoma].

PMID- 14697128
TI  - [Inhibition of survivin expression in liver cancer cells by shRNA].
AB  - OBJECTIVE: To construct the plasmid containing short hairpin RNA (shRNA) of
      survivin in order to suppress the expression of survivin gene in HepG2 and SMMC
      7721. METHODS: Two 20 to 21 bp reverse repeated motifs of survivin target
      sequence with 4 bp or 8 bp spacer were synthesized respectively and inserted into
      plasmid pTZU6+1 to generate the plasmid pshRNA-survivin1 and pshRNA-survivin2;
      plasmid pEGFP-C1-survivin and pshRNA-survivin1 or pshRNA-survivin2 plasmid were
      cotransfected into liver cancer cell HepG2 and SMMC-7721 to detect effect of GFP
      expression respectively and analyze the inhibition of survivin gene. RESULTS: The
      recombinant plasmid pshRNA-survivin1 and pshRNA-survivin2 were successfully
      constructed. The recombinant plasmids suppress the survivin expression by 80% in
      HepG2 and SMMC-7721. CONCLUSION: The result showed that the short hairpin RNA of
      survivin can efficiently suppress it's expression in HepG2 and SMMC-7721.

PMID- 14697129
TI  - [Therapeutic effect of secretive endostatin eukaryotic expressing plasmid on
      mouse hepatoma].
AB  - OBJECTIVE: To construct and express secretive endostatin eukaryotic plasmid for
      treatment of hepatoma. METHODS: Mouse Igk signal peptide sequence was synthesized
      and cloned into pcDNA3.1 with endostatin gene. The supernant of BHK-21
      transfected with recombinant was used to culture ECV304. The proliferation of
      latter was evaluated by MTT assay. H22 was inoculated intramusclely, then naked
      DNA of endostatin plasmid was injected into the inoculation site. Tumors were
      dissected and weighted after treatments. All data was analyzed by SPSS10.0.
      RESULTS: The supernant of BHK-21 transfected with recombinant can inhibit the
      proliferation of ECV304 by 29.2%. Tumor weight lighter after injected with naked
      pSecES (1.34 g+/-0.96g) compared with naked pcDNA3.1 (2.70g+/-0.82g) and saline
      (3.73g+/-1.41g). CONCLUSION: The endostatin eukaryotic plasmid was constructed
      and it can be used for gene therapy on hepatoma.

PMID- 14697130
TI  - [Synergism of an antisense oligodeoxynucleotides targeted to hTERT in combination
      with chemotherapeutic drugs on inhibiting the proliferation of HepG2 cells].
AB  - OBJECTIVE: To investigate the effect of a phosphorothioate antisense
      oligodeoxynucleotide "ASOND" combined with cis-Diamminedichloroplatinum (DDP), 5
      fluorouracil (5-FU) and adriamycin (ADM) respectively on inhibiting the
      proliferation of HepG2 cells. METHODS: A phosphorothioate antisense
      oligodeoxynucleotide (5'-ACTCACTCAGG CCTCAGACT-3') targeted to human telomerase
      reverse transcriptase (hTERT) mRNA, which named cantide, was synthesized. ASODN
      was transfected into HepG2 by lipofectin. And cell growth activity was evaluated
      by MTT assay. SAS software and Jin Zhengjun Method were used to evaluate the
      interaction of ASODN and these chemotherapeutic drugs. RESULTS: Combination
      treatments with 0.1micromol/L ASODN reduced the IC50 of DDP, 5-FU and ADM from
      1.07, 4.15 and 0.29microg/ml to 0.25, 1.52 and 0.12microg/ml respectively. The
      inhibitory ability of combination treatments on HepG2 cells was higher than that
      of these drugs alone (F=66.92, 25.96, 8.56, P<0.001). And synergism (Q>or=1.15)
      was observed at the lower concentration of DDP (<or=1microg/ml), 5-FU
      (<or=10microg/ml) and ADM (<or=0.1microg/ml) with combination of ASODN.
      CONCLUSION: ASODN may enhance therapeutic effectiveness of chemotherapeutic drugs
      in human hepatocellular carcinoma cells.

PMID- 14697131
TI  - [Inhibition of mutant p53 in hepatocellular carcinoma cells by hammerhead
      ribozyme].
AB  - OBJECTIVES: To investigate the inhibition of mutant type p53 in hepatocellular
      carcinoma by hammerhead ribozyme in both cell-free system and MHCC97 cells.
      METHODS: Hammerhead ribozyme genes (RZ) and control ribozyme (asRZ) directed
      against mutant p53 (249 codons, AGG --> AGT) were designed by computer. The in
      vitro transcription plasmid and eukaryotic expression plasmid were constructed
      into the vector pBSKU6 and pEGFPC1. Human mutant and wild type p53 gene fragment
      were cloned into the pGEM-T vector under T7 promoter control. In vitro cleavage
      reaction was carried out by mixing the RZ and target mRNAs which were labeled
      with [alpha-32P] dUTP. RZ was introduced into MHCC97 cells by LipofectAMINEAM2000
      and mtp53 expression was analyzed by RT-PCR. RESULTS: In cell-free systems, RZ
      showed a specific cleavage activity against mtp53 with cleavage efficiency of
      42%, while the wild type p53 was not cleaved. The mRNA level of mtp53 in MHCC97
      cells after transfection was reduced by RT-PCR analysis. CONCLUSION: These
      findings suggest that the hammerhead ribozyme against the mtp53 is a new
      promosing gene therapeutic agent against hepatocellular carcinoma.

PMID- 14697132
TI  - [Study on inhibitory effect of antisense VEGF RNA on the growth of hepatocellular
      in vitro in vivo].
AB  - OBJECTIVE: To determine the effects of PCMV-FGEV transfection on the profile of
      SMMC-7721 hepatocellular in vitro in vivo. METHODS: SMMC-7721 hepatocellular was
      transfected with PCMV-FGEV antisense, PCMV-VEGF sense and empty vector plasmid
      encapsulated by lipofectamine. The positive cell clones were selected with G418.
      The stable transfection and expression of VEGF in the SMMC-7721 hepatocellular
      were determined by in situ hybridization and immunochemical analysis. The effect
      of PCMV-FGEV transfection on SMMC-7721 hepatocellular proliferation was observed
      by MTT colorimetric assay. Flow cytometry was used to determine the effects of
      PCMV-FGEV transfection on cell apoptosis of SMMC-7721. The growth of transfected
      cells was also observed in nude mice. RESULTS: There was reduced VEGF expression
      in SMMC-7721 transfected with PCMV-FGEV confirmed by in situ hybridization and
      immunohistochemical analysis. There was no effect of PCMV-FGEV transfection on
      cell proliferation and cell apoptosis of SMMC-7721 in vitro. The growth of cell
      with PCMV-FGEV transfected was slow in nude mice (vivo) and accompanied with
      obvious apoptosis. The latent time of tumor in the antisense mice group was
      25.0+/-1.8 days, which was longer than that in sense and control group
      significantly (F=19.455, P<0.01). On the other hand, the average tumor weight in
      antisense group (0.96 g+/-0.28 g) was the smallest among the three groups
      (F=21.501, P<0.01). CONCLUSIONS: The expression of VEGF was inhibited by PCMV
      FGEV. There was no effect on cell proliferation and cell apoptosis of SMMC-7721
      by transferring PCMV-FGEV gene into SMMC-7721 cells in vitro. But in vivo it can
      inhibit tumor growth and induce cell apoptosis.

PMID- 14697133
TI  - [The primary study on the anti-HBV effect of whole recombinant yeast].
AB  - OBJECTIVES: Based on the immunologic character of Pichia pastoris yeast, a new
      therapeutic vaccine, whole recombinant yeast, was used to explore a new way to
      activate cell-mediated anti-viral immunity. METHODS: The recombinant plasmids,
      pPIC9K/S and PIC9K/hsp(1-370)-S, were constructed by inserting the gene encoding
      HBsAg, HSP70 (1-370) -HBsAg into vector pPIC9K and then the recombinants were
      transfected into Pichia pastoris yeast,GS115, respectively. Then that recombinant
      yeast immunized BALB/C mice were detected for humoral and cellular immunity to
      HBsAg. RESULTS: Recombinant yeast successfully activated the humoral immunity to
      HBsAg in mice, but failed to activate the cellular immunity. CONCLUSION: The
      whole recombinant yeast can be used as vaccine, but need further study for
      optimal way of immunization.

PMID- 14697134
TI  - [Effects of transforming growth factor beta1 on the proliferation and type I
      collagen expression at different differential rat hepatic stellate cells].
AB  - OBJECTIVES: To investigate the biological responses of cultured hepatic stellate
      cells (HSC) at different differentiated stages on exotic transforming growth
      factor (TGF-beta1). METHODS: HSC was isolated from rat and primarily cultured in
      uncoated disc for 1 d, 4 d and 7 d, when the cells were at quiescent,
      intermediate activated and full activated stages respectively. The cells were
      incubated with 10 pmol/L to 500 pmol/L TGF-beta1 for 24 h, cell proliferation was
      measured with [3H] TdR incorporation, alpha-smooth muscle actin (alpha-SMA) and
      type I collagen protein were assayed with Western blot, and total protein
      secretion in the culture supernatant was analyzed by [3H] proline pulse and
      collagenase digestion. HSC was treated with 100 pmol/L TGF- beta1 for 15 min to
      90 min, and type I pro-collagen mRNA level was assayed by Northern blot. RESULTS:
      TGF-beta1 remarkably inhibited d1 HSC proliferation, the percentage of [3H] TdR
      incorporation at 10 pmol/L to 500 pmol/L TGF-beta1 was 52.8% to 16.8% of the
      control, q value was 5.44 to 10.37 and P<0.01 vs control. But TGF-beta1 had no
      influence on d4 and d7 HSC. As the cells cultivation prolonged and activated, the
      basal levels of alpha-SMA, type I collagen and gene expression increased
      gradually. TGF-beta1 increased the above protein and gene expression. The basal
      and TGF-beta1 stimulated total protein secretion levels at d1-d7 HSC were 804+/
      274 vs 1200+/-708; 2966+/-1701 vs 6160+/-1123, t=3.84, P<0.01; 2580+/-767 vs
      4583+/-1467, t=2.96, P<0.05. While d4 HSC showed the strongest response of total
      protein secretion and alpha-SMA expression. CONCLUSIONS: TGF-beta1 remarkably
      inhibited quiescent HSC proliferation, and promoted HSC collagen production at
      both quiescent and activated HSC. Intermediate HSC had the strongest response to
      TGF-beta1, while activated HSC lost the response to TGF-beta1 inhibitory growth,
      and TGF-beta1 exerted divergent actions on HSC as the cells activated.

PMID- 14697135
TI  - [Study on the angiogenic ability of tumor fibroblasts].
AB  - OBJECTIVES: To explore the role of fibroblasts derived from tumor in the tumor
      angiogenesis. METHODS: Two-well co-culture system were used to detect the
      expression of MMP-9, TGF-beta1, TN and bcl-2 in L929-H22 cells, and their ability
      of promoting angiogenesis of ECV304 cells and invasion of MDA-MB-231 cells
      respectively, which were established in our laboratory before. Then their
      adhesion and the effect of their supernatant on H22 cells proliferation were
      analysed. RESULTS: Compared with L929 cells, the adhesion potential of L929-H22
      cells increased (F>or=104.32, P<0.001), with the higher level of expression of
      MMP-9, bcl-2, TN, and TGF-beta1 in L929-H22 cells in creased (t>or=3.3055,
      P<0.01). L929-H22 and L929 cells enhanced the invasiveness of human mammary
      cancer MDA-MB-231 cells through artificial basement membrane (Matrigel) 1.21 and
      0.48 times respectively (F=266.3, P<0.001). L929-H22 cells induced morphogenesis
      of ECV304 cells. L929-H22 stimulated endothelial cells to form more and longer
      tubes than L929 did (F>or=23.75, P<0.01). 25% CM of L929-H22 cells stimulated the
      growth of H22 cells (F=266.30, P<0.05). CONCLUSION: The results suggested that
      fibroblasts in tumors secrete more growth factors and angiogenic factors to
      promote the angiogenesis and invasion of solid tumors.

PMID- 14697136
TI  - [Changes of alkaline phosphatase sugar chains in hepatocellular carcinoma
      tissue].
AB  - OBJECTIVE: To investigate the changes of sugar chain structures of alkaline
      phosphatase (ALP) in hepatoma tissue and its relation to the invasiveness of
      hepatocellular carcinoma (HCC). METHODS: The binding ratios of ALP from 9 normal
      liver tissues, 16 hepatoma tissues and 16 noncancerous tissues surrounding
      hepatoma were analysed by affinity chromatography on various lectin columns
      including leukoagglutinating phytohemagglutinin (L-PHA), lentil lectin (LCA),
      Datura stramonium agglutinin (DSA), erythroagglutinating phytohemagglutinin (E
      PHA) and Sambucus nigra bark agglutinin (SNA). RESULTS: The binding ratios of ALP
      on L-PHA (22.94%+/-5.30%), DSA (55.97%+/-13.72%), LCA (38.16%+/-8.87%), E-PHA
      (11.56%+/-4.81%) and SNA (69.80%+/-13.71%) in HCC tissues were significantly
      increased (P<0.01) compared with that in normal liver tissues (L-PHA 5.89%+/
      2.75%, DSA 36.20%+/-11.58%, LCA 17.90%+/-6.71%, E-PHA 5.38%+/-2.20%, SNA 57.32%+/
      11.27%), respectively. t values between the two groups were 8.94, 3.64, 5.94,
      3.62 and 2.32, respectively. L-PHA-binding ratio (25.84%+/-4.67%) of ALP in HCC
      with invasiveness was significantly higher than that (18.10%+/-3.64%) without
      invasiveness (t=3.71, P<0.01). CONCLUSION: The changes of ALP sugar chain
      structures occur in HCC tissue. b1-6 branching sugar chain structure of ALP is
      related to the invasiveness of HCC.

PMID- 14697137
TI  - [Different effects of several signal pathway after liver transplantation].
AB  - OBJECTIVES: To explorer the change of several signal pathway and their signal
      after liver transplantation. METHODS: Classified 34 punctured donor liver samples
      and 10 normal liver samples as A (no rejection) groups, B (mild/moderate acute
      rejection) groups, C (serious acute rejection) groups, D (chronic
      rejection/fibrosis) groups and E (control) groups, MAPK, Ras and p53 were
      performed immunohistochemistry analysis and image analysis. MAPK and Ras were
      performed in situ hybridizition. Then image analysis was performed. RESULTS: The
      protein expression of MAPK, Ras, increase by turns of A, B and C groups (1.42+/
      0.28, 3.88+/-0.87, 6.68+/-0.57 in MAPK; 1.27+/-0.12, 2.80+/-0.30, 3.93+/-0.20 in
      Ras; corresponding), and decrease by turns of D and E groups (1.49+/-0.37, 0.88+/
      0.20 in MAPK; 1.47+/-0.21, 1.01+/-0.12 in Ras; corresponding, F=178.39 in MAPK
      and 320.59 in Ras, groups B, C vs groups A, D, E, P<0.001 in MAPK and Ras), The
      protein expression of p53 is higher in treated groups (The results of groups A to
      E are 2.09+/-0.13, 2.39+/-0.11, 2.03+/-0.19, 2.26+/-0.18 and 0.35+/-0.08,
      corresponding, F=360.08, groups E vs groups A, B, C, D, P<0.001). Expression of
      MAPK, Ras mRNA is as same as that of protein. CONCLUSION: The MAPKs pathway has
      role in rejection response after liver transplantation. And it seemed that the
      MAPKs and p53 are one regulation mechanism for protecting the hepatocyte from
      damage after liver transplantation.

PMID- 14697138
TI  - [The biological activity of MHC classII transactivator ribonuclease P: a novel
      approach for hepatic transplantation rejection].
AB  - OBJECTIVE: This paper studied the effect of RNaseP against CIITA on repressing
      class II MHC (MHCII) expression. METHODS: It was constructed that M1-RNA with
      guide sequences (GS), recognizing the 629 site of CIITA (M1-629-GS), by PCR from
      pTK117 plasmid, then was cloned into psNAV (psNAV-M1-629-GS). CIITA target gene
      was obtained from Raji cell by RT-PCR, and then inserted into pGEM-7zf (+) (pGEM
      800). psNAV-M1-629-GS and pGEM-800 were transcribed and then mixed up and
      incubated in vitro. Stable transfectants of hepatocyte with psNAV-M1-629-GS by
      nanometer were tested for MHCII induction by recombinant human interferon-gamma
      (IFN-gamma). mRNA abundance of CIITA was measured by RT-PCR. RESULTS: It showed
      that M1-629-GS could exclusively cleave pGEM-800 that formed a base pair with the
      GS. When induced with IFN-gamma, the expression of HLA-DR, -DP, -DQ on psNAV-M1
      629-GS+ hepatocyte was (1.01+/-0.51)%, (4.37+/-1.28)%, (1.98+/-0.42)%
      respectively, was down-modulated 90.65%, 89.11% and 65.32% compared with control,
      while the mRNA content of CIITA reduced significantly (P<0.01). CONCLUSION: M1
      629-GS could effectively repress MHCII expressing through cleaving CIITA mRNA.
      These results provided insight into the future application of it as a new nucleic
      acid drug against the rejection of hepatic transplantation.

PMID- 14697139
TI  - [Detection of platelet-derived growth factor-AB in patients'sera with hepatic
      cirrhosis pre- and post- splenectomy].

PMID- 14697140
TI  - [The clinical management of cardiovascular complications after orthotopic liver
      transplantation].
AB  - OBJECTIVE: To report the incidence and analyze the factor predisposing to
      cardiovascular complication after orthotopic liver transplantation (OLTx).
      METHODS: A retrospective study was made for the patients who develop of all cases
      in which patients presented with cardiovascular complications after OLTx from
      April 1993 to December 2001 in the First Affiliated Hospital of Sun Yat-sen
      University, Guangzhou. RESULTS: Eighty-nine liver transplants were performed in
      88 patients. Cardiovascular complications developed in 65 (73%) patients. Among
      these 65 complications, 6 were myocardiac ischemia, 9 were heart failure, 59 were
      hypertension and 5 were pulmonary hypertension. portoperative mortality rate
      related to cardiovascular complication was 12.4% (11/89). Except for the
      preexisting coronary artery disease, the unbalance between coagulant and
      anticoagulant function in patients after OLTx may play a role in myocardiac
      ischemia after OLTx. Heart failure was correlated with massive intraoperative
      blood transplantation (chi2=5.714, P<0.05). CONCLUSION: Cardiovascular
      complications are common after OLTx. They are severe and highly related to
      mortality. The unbalance between coagulant and anticoagulant function in patients
      after OLTx resulting in the thrombosis in coronary artery may be the cause of
      myocardiac ischemia. Massive intraoperative blood transplantation may be
      responsible for heart failure.

PMID- 14697141
TI  - [Effect of interferon combined with lamivudine in treatment of chronic hepatitis
      B patients infected with HBV with mutation of YMDD].

PMID- 14697142
TI  - [Therapeutic effect of lamivudine on liver fibrosis resulted from chronic
      hepatitis B].

PMID- 14697143
TI  - [Studies on the correlation between titer of antibodies against different
      function regions of hepatitis C virus and HCV RNA of chronic patients].
AB  - OBJECTIVE: To detect humoral immune response against different function regions
      of hepatitis C virus (HCV) in chronic patients, and further to investigate the
      correlativity between anti-HCV antibody titers and HCV RNA concentration.
      METHODS: Using recombinant dominate epitope antigens, e.g. HCV Core, NS3, NS4,
      NS5 and chimeric HVR1, a set of ELISA test reagents was formulated. Then, titers
      of antibodies against HCV different regions and the RNA concentration of HCV in
      chronic patient sera were detected by ELISA and quantitative RT-PCR technique,
      respectively. RESULTS: Great differences have been noted in antibody titers and
      positive rate of different HCV function regions in chronic patients. Antibodies
      against HCV Core and HVR1 have the highest positive rate, then NS3, NS4, and NS5
      in sequence. CONCLUSION: The titer of antibodies against different regions of HCV
      in chronic patients has good correlation with HCV RNA concentration.

PMID- 14697144
TI  - [Gene therapy for hepatocellular carcinoma].

PMID- 14697145
TI  - [Current status and progress of immunotherapy for hepatocellular carcinoma].

PMID- 14697146
TI  - [The relationship between plasma procalcitonin, endotoxin and renal function
      status in patients with cirrhotic ascites].

PMID- 14697147
TI  - [Correlation between thromboelastogram and activated clotting time in liver
      transplantation].

PMID- 14697148
TI  - [Radiofrequency ablation therapy of hepatic neoplasms].

PMID- 14697149
TI  - [Current status and progress of tumor vaccine for hepatocellular carcinoma].

PMID- 14697150
TI  - [Hepatocellular carcinoma: its blood supply and interventional management].

PMID- 14697151
TI  - [The molecular mechanism of warm ischemia-reperfusion injury in liver graft].

PMID- 14697152
TI  - Intensity-modulated radiation therapy for head and neck cancer.
AB  - Intensity-modulated radiation therapy (IMRT) involves the delivery of optimized
      nonuniform beam intensities to the patient. In the head and neck region, there
      are many critical structures in close proximity to the target, with little
      influence from internal organ motion. Because IMRT produces tightly conformal
      doses and steep-dose gradients next to normal tissues, it provides the potential
      for organ sparing and improved tumor control. The dosimetric superiority of head
      and neck IMRT over conventional techniques has been demonstrated. The initial
      results of clinical IMRT studies showed reduction in xerostomia with no
      compromise in locoregional control if caution and appropriate knowledge are
      exercised in target determination and delineation.

PMID- 14697153
TI  - Salivary gland neoplasms.
AB  - Treatment and cure of salivary gland neoplasms requires surgical intervention in
      most cases. For parotid neoplasms, the most common surgical procedure performed
      is the superficial parotidectomy with facial nerve preservation. Postoperative
      radiation therapy is indicated in high-grade salivary gland malignancies and
      malignancies with increased risk of locoregional recurrence. Primary radiation,
      including neutron beam techniques, may play a role in certain histologic types or
      nonoperative candidates. Chemotherapy has yet to result in improvements in
      survival or quality of life in the treatment of salivary gland malignancy.
      Advances in radiation therapy techniques, including intensity-modulated radiation
      therapy, provide opportunities for reduced morbidity.

PMID- 14697154
TI  - Costimulation-based immunotherapy for head and neck cancer.
AB  - Squamous cell carcinoma of the head and neck (SCCHN) is an important source of
      cancer-related morbidity and mortality worldwide. Current treatment options are
      founded on various combinations of surgery, radiation therapy, and chemotherapy,
      with implementation largely based on patient/disease-specific factors and
      provider/institutional bias. Despite improvements in surgical techniques and the
      development of novel chemoradiotherapy strategies for organ preservation,
      survival has remained relatively unchanged in the past 30 years. Additionally,
      the impact of these novel treatment approaches on the quality of life of patients
      remains largely unknown. Improvements in survival and the quality of life for
      patients with SCCHN will likely require the development of new therapeutic
      alternatives based on the improved understanding of the molecular pathogenesis of
      SCCHN and associated changes in the immune response.

PMID- 14697155
TI  - Controversies in management of the neck in head and neck cancer.
AB  - As definitive external radiation and multimodality organ preservation strategies
      (eg, combined chemotherapy and radiation therapy ) improve, the role of surgery
      is being re-examined in the management of locally advanced head and neck cancer.
      Consensus regarding the use of neck dissections for complete responders and
      incomplete responders has yet to be achieved and the data are surprisingly
      controversial. A possible benefit from neck dissection after a complete response
      of the primary tumor after CCRT or definitive external radiation for advanced
      squamous cell carcinoma of the head and neck may only be anticipated in patients
      with persisting subclinical neck disease who have no other sites of disease. Some
      clinicians have even argued that the salvage rate for clinically detectable
      residual neck disease does not justify neck dissection. Randomized data
      addressing these questions and a trial addressing the accuracy of new imaging
      modalities, such as postchemotherapy and postradiation positron emission
      tomography scanning, across multiple institutions would be appropriate. As a
      department, we are aggressive in our treatment of isolated residual neck disease
      after CCRT or definitive external radiation and for patients initially diagnosed
      with N3 nodal disease. We are investigating the use of adjuvant neck
      brachytherapy at the time of neck dissection and we are pleased with our early
      results.

PMID- 14697156
TI  - Prophylactic cranial irradiation in lung cancer.
AB  - Patients with locally advanced lung cancer (non-small cell lung cancer or small
      cell lung cancer ) are threatened by concurrent risks of local, regional, and
      distant failure. By improving locoregional and systemic control within
      multimodality protocols, the brain emerges as one of the major relapse sites;
      therefore, prevention of brain relapse has become a primary focus of attention.
      Prophylactic cranial irradiation (PCI) has a high potential to reduce the risk of
      brain metastases. Clear evidence exists from meta-analysis that PCI improves
      overall and disease-free survival rates for patients with SCLC in complete
      remission. Long-term toxicities, predominantly neurocognitive impairments,
      represent potential risks, but within large prospective trials, including
      adequate control groups, late complications of clinical significance rarely have
      been observed. PCI is the recommended standard of care for the patients with
      limited disease SCLC in complete remission. As long as the optimal dose and
      fractionation remain to be defined in this setting, conventional fractionation
      with moderate total doses of approximately 30 Gy is preferred. In patients with
      locally advanced stage III non-small cell lung cancer treated within
      multimodality protocols, comparable relative risks for cumulative brain relapse
      have been demonstrated in long-term survivors. Although not the standard of care
      in this situation, the scientific community should be encouraged to further
      investigate PCI in these patient subgroups within carefully designed clinical
      trials, including untreated control arms.

PMID- 14697157
TI  - Management of paraneoplastic syndromes in lung cancer.
AB  - Paraneoplastic syndromes are common complications of lung cancer. Although most
      frequently associated with advanced disease, paraneoplastic syndromes may also
      occur at early stages. Occasionally, the paraneoplastic syndrome may be the
      presenting symptom of lung cancer. For most paraneoplastic syndromes, the best
      treatment is to treat the underlying malignancy. However, in many cases,
      treatment of moderate efficacy or urgent therapy is required. Specific
      recommendations for the management of the most common paraneoplastic syndromes,
      including cachexia, hypercalcemia, and hyponatremia, are provided.

PMID- 14697158
TI  - Positron emission tomography scanning for the diagnosis and management of lung
      cancer.
AB  - The dissemination of positron emission tomography (PET) technology has enabled a
      functional approach to the evaluation of lung cancer that complements the
      anatomic assessment provided by chest radiography, computed tomography (CT)
      scanning, and magnetic resonance imaging. PET has excellent sensitivity and good
      specificity for the determination of malignancy in the solitary pulmonary nodule,
      but these data must be weighed against the evidence of instances of false
      positive results because of inflammatory lesions and false-negative results in
      small- or low-metabolism neoplasms. Therefore, PET may not be advisable when
      these scenarios apply. Furthermore, in a patient with a very high pretest
      likelihood of lung cancer (eg, a new or enlarging spiculated nodule in a long
      time smoker), the value of PET is less certain because a negative result may be
      discounted. PET has altered the approach to the staging of lung cancer. It adds
      value to the evaluation of the mediastinum and extrathoracic structures compared
      to conventional methods by upstaging or downstaging a substantial proportion of
      patients. If the staging assessment is negative on PET, the use of
      mediastinoscopy may be obviated in selected cases. Histologic confirmation of
      positive PET findings should be obtained before excluding patients from curative
      resection. PET provides incremental information to CT in the evaluation of
      persistent and recurrent disease, and response measured on PET appears more
      accurate as a predictor of ultimate survival. The more recent development of PET
      CT permits fusion of anatomic and functional information. Early investigations
      suggest that this strategy provides superior results compared to either technique
      alone.

PMID- 14697159
TI  - Cardiopulmonary rehabilitation after treatment for lung cancer.
AB  - Lung cancer is the leading cause of cancer-related death in women and men in the
      United States. As of 1987, lung cancer deaths in women exceeded deaths caused by
      breast cancer. Despite years of research and improvements in surgical,
      chemotherapeutic, and radiation treatments, this fact remains unchanged. Equally
      dismal is that the expected 5-year survival rate for all patients with lung
      cancer is 15%. Although hidden in this number is improved survival for many
      patients who have early disease, it still translates into significant morbidity
      and early mortality for many patients. Although prevention is key, optimizing the
      care of these patients with lung cancer is also paramount. Cardiopulmonary
      rehabilitation programs have been shown to be effective in treating patients with
      chronic heart and lung diseases, among other illnesses, regardless of
      prerehabilitation functioning. Not only do morbidity and mortality from cancer
      hinge directly on premorbid functioning, health, and status, but functional
      status as a measure of baseline health is a reliable prognostic indicator for
      patients with lung cancer. As a result, including a program of exercise in any
      treatment regimen for cancer is sensible. However, rehabilitation in patients
      with lung cancer has not been studied well. Data on rehabilitation in patients
      with other cancers and illnesses (eg, chronic obstructive pulmonary disease) are
      clear in the beneficial effects of supervised exercise on quality of life (QOL).
      To assess the role of cardiopulmonary rehabilitation in patients with lung cancer
      undergoing treatment, it is necessary to meld studies regarding patients with
      noncancerous conditions with studies addressing rehabilitation in patients with
      cancer. This fusion of information demonstrates that rehabilitation results in
      significant improvements in QOL in patients who participate, regardless of the
      disease in question. Although QOL may not always have been an obvious endpoint
      for treating patients with lung cancer, it is apparent from studies of the
      patients themselves that an improved QOL is far more important than other goals
      of therapy.

PMID- 14697160
TI  - [Randomized, prospective and comparative clinical trial of
      piperacillin/tazobactam versus ceftriaxone plus ornidazole in the treatment of
      biliary tract infections].
AB  - BACKGROUND AND OBJECTIVE: The treatment of biliary tract infections requires
      antibiotics and an appropriate surgical procedure. The aim of this study was to
      evaluate the efficacy and safety of piperacillin/tazobactam versus ceftriaxone
      plus ornidazole in the treatment of biliary tract infections. PATIENTS AND
      METHOD: This was a randomized, prospective and comparative clinical trial of two
      antibiotic regimens in the treatment of biliary tract infection. One hundred and
      fifty three patients were randomly allocated into two groups; three patients were
      excluded after randomization. One group (n = 75) received piperacillin/tazobactam
      (4 g/8 h iv) and the other group (n = 75) was administered a combination of
      ceftriaxone (2 g/24 h iv) plus ornidazole (1 g/24 h iv). In both groups,
      protocolized surgical or endoscopic procedures were carried out. Clinical
      efficacy and safety were assessed at the end of treatment. RESULTS: Demographic
      data and severity of disease were similar in both groups. Three patients were
      excluded of the study by deviations from the protocol. Sixty-seven patients
      (89.3%) out of the piperacillin/tazobactam group and sixty-six patients (88%) out
      of the ceftriaxone plus ornidazole group were clinically cured (OR = 0.87 [95%
      CI, 0.31-2.4]). Twelve patients died, seven in the piperacillin/tazobactam group
      and five in the ceftriaxone plus ornidazole group. Adverse events were similar in
      both groups (OR = 1.18 [95% CI, 0.37-3.7]). CONCLUSIONS: This study suggests that
      piperacillin/tazobactam is as efficacious and safe as ceftriaxone plus ornidazole
      in the treatment of biliary tract infections.

PMID- 14697162
TI  - [Analysis of the Spanish situation regarding folic acid/calcic folinate
      consumption for birth defects prevention].
AB  - BACKGROUND AND OBJECTIVE: Since 1992, the recommendation on the ingestion of
      folic acid (FA) to prevent congenital defects has become general in developed
      countries. In this paper, we analyze such a situation in Spain in most recent
      years. PATIENTS AND METHOD: We used the information concerning mothers of infants
      selected as controls in the ECEMC database. These mothers make up a sample of
      pregnant women of the general population. We analyzed the evolution of the
      consumption of FA/calcic folinate (CF) by pregnant women over the last 22 years,
      considering the period of pregnancy during which this vitamin was taken and the
      dosage. RESULTS: The proportion of women who take FA/CF during the first
      trimester of pregnancy increased dramatically in the last 9 years, up to 80% in
      2002. However, only about 9% took the vitamin before becoming pregnant. Moreover,
      many daily doses are much higher than those internationally recommended for the
      general population of women planning pregnancy. CONCLUSIONS: In our country, the
      use of FA/CF to prevent congenital defects is correct in a small part of the
      population of pregnant women. Therefore, it is necessary to continue
      disseminating appropriate guidelines not only among gynecologists but also among
      family and general practitioners and health professionals working at family
      planning centers. Thus, they can transmit to women the need of using FA/CF and
      the right way to do it.

PMID- 14697161
TI  - [Prospective validation of a clinical scoring system for the diagnosis of organic
      dyspepsia].
AB  - BACKGROUND AND OBJECTIVE: Predictive symptomatic scoring models have been
      proposed to select patients with dyspepsia, who may be candidates to endoscopy.
      In a previous study performed by gastroentrologists from our group, we obtained
      three scales of symptoms to predict organic dyspepsia, peptic ulcer and
      esophagitis, respectively. Here we analyze the reproducibility of those scoring
      models of symptoms when used either by other gastroenterologists or general
      practitioners. PATIENTS AND METHOD: It was a clinical prospective study of 230
      patients from the Viladecans hospital area (120 from primary healthcare and 110
      from the gastroenterologist's consultation). The three validation scales were
      performed in each patient. Then, we performed a diagnostic gastroscopy which
      allowed to classify patients into those with organic dyspepsia (ulcer,
      esophagitis, cancer) or those with functional dyspepsia. We calculated the
      overall predictive accuracy for the gastroenterologist and the general
      practitioner and for the three diagnoses (organic dyspepsia, ulcer or
      esophagitis) using the C statistic. RESULTS: Discriminative capacities were 0.75
      and 0.82 for organic dyspepsia, 0.78 and 0.86 for ulcer disease, and 0.78 and
      0.82 for esophagitis, for the general practitioner and the gastroenterologist,
      respectively. In this validation study, the best cut-off value, namely the one
      combining good sensitivity and specificity, was found to be 7. CONCLUSIONS: A
      correct predictive capacity of the symptomatic score models when used by other
      gastroenterologists or by primary healthcare practioners confirms its
      reproducibility and transferability. The use of predictive symptomatic score
      models in everyday clinical practice can allow to rationalize the referral for
      endoscopy in our local setting.

PMID- 14697163
TI  - [Somu's formula in the diagnosis of hypertension in Spanish children and
      adolescents].
AB  - BACKGROUND AND OBJECTIVE: Several formulae for the diagnosis of hypertension in
      children and adolescents have recently been published. We analyzed the usefulness
      of the formulae as a tool for the diagnosis of hypertension. MATERIAL AND METHOD:
      Concordance analysis between formula's predicted values for 95 percentile values
      in Spanish reference charts (RICARDIN study) for each age and sex and its
      diagnostic efficiency in the diagnosis of hypertension. RESULTS: Concordance
      values between pairs were: systolic blood pressure (SBP) 6 to 17 years 0.87 (95%
      CI, 0.73-0.94; p < 0.0001), diastolic blood pressure (DBP) 6-10 years 0.89 (95%
      CI, 0.63-0.97; p < 0.0001), and DBP 11-17 years 0.54 (95% CI, 0.03-0.82; p <
      0.05). Taking the formula's predicted value as a cut point, area under ROC values
      were: SBP 0.929 (95% CI, 0.895-0.962), DBP 6-10 years 0.8 (95% CI, 0.663-0.937)
      and DBP 11-17 years 0.518 (95% CI, 0.394-0.642). CONCLUSIONS: An adecuate
      concordance was obtained. However, the application of the formulae to Spanish
      children and adolescents leads to several false positive results for SBP and
      false negative results for DBP, mainly in children over 11-years-old. Alternative
      formulae based on data obtained in Spanish children and adolescents are proposed.

PMID- 14697164
TI  - [Biliary tract infection: which antibiotics and in which setting].

PMID- 14697166
TI  - [Comittment with suffering and empathy].

PMID- 14697165
TI  - [Primary prevention of neural tube defects].

PMID- 14697167
TI  - [Hepatitis E virus: current status].
AB  - In areas with tropical or subtropical climate and poor sanitary conditions,
      hepatitis E is the major cause of enterically transmitted non-A, non-B hepatitis,
      and is responsible for both water-borne outbreaks and sporadic cases of acute
      hepatitis. The causative agent is the hepatitis E virus (HEV), a non-enveloped,
      single-stranded, positive-sense RNA molecule of an approximately 7.2 kb length.
      Recently, HEV strains have been isolated in swine in industrialized countries. In
      addition, cases of acute hepatitis due to novel HEV variants have been reported
      in humans without recognized risk factors for hepatitis E in Europe, Japan and
      the US. Some of the novel strains were found to be closely related to swine HEV
      isolates from the same area, suggesting that hepatitis E is a zoonotic disease.
      Thus hepatitis E is becoming a concern in countries where HEV is not,
      traditionally, believed to be endemic. This review summarizes the current
      knowledge of the biology, structure and transmission of the virus as well as the
      diagnosis of the infection. We also analyze the present status in areas with a
      low incidence of acute hepatitis E and the role of animals as potencial vectors
      of the virus.

PMID- 14697168
TI  - [Evaluation of external reliability between two scientific journal publications
      in the last five years].

PMID- 14697169
TI  - [Adrenal carcinoma: an unfrequent cause of severe hypokalemia].

PMID- 14697170
TI  - [Treatment of empyema and complicated parapneumonic effusions with pleural
      fibrinolytics].

PMID- 14697171
TI  - [Treatment of empyema and complicated parapneumonic effusions with pleural
      fibrinolytics].

PMID- 14697173
TI  - [Mortality due to heatstroke in forensic medicine. Epidemiological implications].

PMID- 14697174
TI  - [Primary MALT lymphoma arising in dura in a 33 years old woman].

PMID- 14697175
TI  - [Observation areas in emergency department. Review of their use].

PMID- 14697176
TI  - [Family medicine and adolescence].

PMID- 14697177
TI  - [Good morning, Mr. Representative. Anything new to tell us about? Analysis of the
      pharmacological products introduced by the drugs industry into a health
      district].
AB  - OBJECTIVE: To study whether the visits of technical health representatives (ITS)
      mean that new drugs are introduced. Design. Prospective, descriptive study.
      SETTING: Urban health centre. PARTICIPANTS: The products presented by 137 ITS
      from 83 drug laboratories in weekly sessions for a year were studied. MAIN
      MEASUREMENTS: The products presented, the year they were first marketed,
      intrinsic value (IV), newness and use potential, cost per package and defined
      daily dose and material handed over were studied. RESULTS: 472 drug products were
      introduced. The most common ones belonged to the cardiovascular group (27.3%),
      digestion and metabolism (14.8%) and anti-infection drugs (13.3%). 65.5% had been
      on the market for <5 years. 84.3% had a high IV. Only 31 products (6.6%) were new
      (95% CI, 4.5-9.2). 71% of these supposed no or very slight therapeutic
      improvement, 25.8% a modest improvement and 3.2% a major improvement. Mean cost
      was 19.3 euros per package and 2 euros per DDD, with significant differences
      found (P<.006) on stratifying by date of marketing (more recently marketed
      products cost more). 61% of the products were presented with additional material
      (leaflets, monographs, journals), 21.6% with gifts of symbolic value, and 19.9%
      with samples of the product. There were significant differences (P<.03) between
      the new drugs and the normal prescriptions issued at the centre. In the new
      drugs, there were fewer products with high IV and cost per package and per DDD
      was higher. CONCLUSIONS: The products introduced by the reps do not include any
      important new drugs. They are presented with abundant back-up and are more
      expensive than those normally prescribed.

PMID- 14697178
TI  - [The regulation of medical visits: necessary but insufficient].

PMID- 14697179
TI  - [Validation of the Spanish version of the Modified Stanford Health Assessment
      Questionnaire (MSHAQ), an instrument to measure people's satisfaction at their
      ability to perform normal day-to-day activities].
AB  - OBJECTIVES: To design a Spanish version of the Modified Stanford Health
      Assessment Questionnaire (MSHAQ), and to evaluate its reliability, internal
      consistency and validity of construction. DESIGN: Adaptation using the
      translation and back-translation method, which focused on ensuring the conceptual
      equivalence of each item. For the validation study, a cross-sectional study was
      conducted.Participants. 52 people over 65 being monitored for a chronic clinical
      condition. MAIN MEASUREMENTS: As well as anamnesis and the Barthel index,
      subjects were asked to answer the Spanish version of the MSHAQ on the day of
      their visit and three days afterwards to evaluate test-retest reliability.
      RESULTS: A sample of 52 people, 23 men and 29 women, with a mean age of 74.2 (SD,
      5.8) was examined. Study of test-retest reliability showed an intra-class
      correlation coefficient (ICC) of 0.89, 0.82, 0.88 and 0.51 for Tables A
      (capacity), B (satisfaction), C (need for help), and D (change in the last 6
      months) of the MSHAQ. These four sub-scales were internally consistent, with
      Crombach's alpha of 0.83, 0.76, 0.61, and 0.82, respectively. There was a
      statistically significant correlation between all the tables in the questionnaire
      and between these and Barthel's index. CONCLUSIONS: It can be concluded that the
      Spanish version of the MSHAQ is a valid and reliable measuring instrument, which
      enables studies performed in various countries to be compared.

PMID- 14697180
TI  - [Pre-malignant and malignant lesions in minor surgery at a health centre.
      Appearances can't be trusted].
AB  - OBJECTIVE: To describe the characteristics of the malignant and pre-malignant
      lesions found in the minor surgical interventions performed at a health centre.
      DESIGN: Retrospective, descriptive study. PARTICIPANTS: 682 lesions: all the
      lesions extirpated and referred to pathology except for epidermal and
      trichilemmal cysts, lipomas, molluscum, common warts, and nails. SETTING:
      Rochapea Health Centre, Pamplona.Main measurements. We analysed the anatomical
      pathological results and the distribution by sex, age-group, location, technique
      and edges affected in 27 dysplasias and 11 malignant lesions. RESULTS: We found
      that malignant and pre-malignant lesions were more common in women, aged 15 to 44
      for dysplasias and 45-64 for malignant lesions. The most common location was on
      the back; the most frequent technique, fusiform excision. This technique had the
      highest percentage of edges without lesion in dysplasias. The lesions whose edges
      were affected corresponded to punch and circular excision samples. None of the
      malignant lesions had their edges affected. CONCLUSIONS: Most malignant lesions
      are not suspected. They appear in samples referred with a diagnosis of benign.
      Employment of techniques such as fusiform excision in lesions which are
      potentially malign, even though in principle they seem benign, enables them to be
      extirpated with free edges.

PMID- 14697181
TI  - [Calculation of coronary risk in the 35-60 year old population registered at a
      health centre].
AB  - OBJECTIVES: To stratify the population between 35 and 60 years old according to
      their coronary risk (CR) and to identify the modifiable cardiovascular risk
      factors that affect our population. DESIGN: Transversal, descriptive study.
      SETTING: Cabanaquinta Health Centre, in a rural health district in Asturias area
      VII.Participants. Simple randomised sampling based on the health cards of the
      population between 35 and 60 years old assigned to a health centre. Total number
      of people included was 205, and 95 did not reply. MAIN MEASUREMENTS: The
      variables were: age, sex, total cholesterol, HDL-cholesterol, triglycerides,
      diastolic blood pressure, systolic blood pressure, tobacco dependency, diabetes,
      hypertension treatment, treatment for lipaemia, and personal background of
      cardiovascular disease (CVD). CR was calculated with the ATP-III tables (Adult
      Treatment Panel III). High CR was understood as over 20% likelihood of developing
      CVD or having recurrent episodes of CVD in the next 10 years. RESULTS: A simple
      descriptive study was conducted. 53% were women; mean age was 48. 37% were
      smokers, 27% with lipaemia and 29% with hypertension. Mean systolic pressure was
      126 mm Hg, mean diastolic pressure was 80 mm Hg. Cholesterol was 213 mg/dL
      (confidence interval [CI], 174-252), HDL-cholesterol 52.64 mg/dL (CI, 39.94
      65.34), LDL-cholesterol 139 mg/dL (CI, 104-174) and triglycerides 106.02 mg/dL
      (CI, 19.72-192.32). 45% of the sample had two or more CV risk factors. Mean CV
      risk in the population was 5.3% (CI, <1%-11.3%). According to the table used, 2%
      of the population had high CR. CONCLUSIONS: Most of our population had moderate
      risk. The most common group of patients is a young woman smoker with moderate
      risk. Tobacco is the most prevalent modifiable risk factor.

PMID- 14697182
TI  - [Repercussions on primary care of Act 41/2002 on patient autonomy, right to
      information and clinical documents (I)].

PMID- 14697183
TI  - [Evaluation of cardiovascular risk. What table to use?].

PMID- 14697184
TI  - [Cannabis consumers: a therapeutic intervention based on programmes of damage and
      risk reduction].

PMID- 14697185
TI  - [What style of consultation with my patients should I adopt? Practical
      reflections on the doctor-patient relationship].

PMID- 14697186
TI  - [Accidental poisoning of children at Requena General Hospital (1997-2002)].

PMID- 14697187
TI  - [Clinical scales in patients with multiple sclerosis in primary care].

PMID- 14697188
TI  - [Inappropriate ADH secretion syndrome associated with sertraline].

PMID- 14697189
TI  - [Functional status after hip fracture in the elderly].

PMID- 14697192
TI  - [Improper consumption of macrolides].

PMID- 14697190
TI  - [Use of viagra as treatment for erectile dysfunction as a side-effect of anti
      depressants].

PMID- 14697193
TI  - [Further thoughts on sampling techniques].

PMID- 14697195
TI  - Memory, synaptic translation, and...prions?
AB  - Two papers from Kausik Si, Eric Kandel, Susan Lindquist, and colleagues set forth
      a bold new idea for thinking about the mechanisms underlying the generation and
      maintenance of long-term memories (Si et al., 2003a, 2003b [this issue of Cell]).

PMID- 14697196
TI  - The enemy at the gates. Ca2+ entry through TRPM7 channels and anoxic neuronal
      death.
AB  - In brain ischemia, gating of postsynaptic glutamate receptors is thought to
      initiate Ca2+ overload leading to excitotoxic neuronal death. In this issue,
      Aarts and colleagues describe a novel mechanism, whereby gating of TRPM7, a Ca2+
      permeable nonselective cation channel, mediates Ca2+ overload and demise of
      anoxic neurons.

PMID- 14697197
TI  - Plasmodium biology: genomic gleanings.
AB  - The highly A+T rich genomes of human and rodent malarial parasites offer
      unprecedented glimpses of a lineage that is distinct from other model organisms.
      Plasmodium is distinguished by the presence of numerous low complexity inserts
      within globular domains of proteins. It displays several peculiarities in its
      transcription apparatus, and its DNA repair system appears to favor a certain
      innate level of mutability. Plasmodium possesses many cell surface molecules with
      "animal-like" adhesion modules. Potential genetic footprints of the ancestral
      eukaryotic algal precursor of the apicoplast are also detectable in its genome.

PMID- 14697198
TI  - Prediction of mammalian microRNA targets.
AB  - MicroRNAs (miRNAs) can play important gene regulatory roles in nematodes,
      insects, and plants by basepairing to mRNAs to specify posttranscriptional
      repression of these messages. However, the mRNAs regulated by vertebrate miRNAs
      are all unknown. Here we predict more than 400 regulatory target genes for the
      conserved vertebrate miRNAs by identifying mRNAs with conserved pairing to the 5'
      region of the miRNA and evaluating the number and quality of these complementary
      sites. Rigorous tests using shuffled miRNA controls supported a majority of these
      predictions, with the fraction of false positives estimated at 31% for targets
      identified in human, mouse, and rat and 22% for targets identified in pufferfish
      as well as mammals. Eleven predicted targets (out of 15 tested) were supported
      experimentally using a HeLa cell reporter system. The predicted regulatory
      targets of mammalian miRNAs were enriched for genes involved in transcriptional
      regulation but also encompassed an unexpectedly broad range of other functions.

PMID- 14697199
TI  - Size selective recognition of siRNA by an RNA silencing suppressor.
AB  - RNA silencing in plants likely exists as a defense mechanism against molecular
      parasites such as RNA viruses, retrotransposons, and transgenes. As a result,
      many plant viruses have adapted mechanisms to evade and suppress gene silencing.
      Tombusviruses express a 19 kDa protein (p19), which has been shown to suppress
      RNA silencing in vivo and bind silencing-generated and synthetic small
      interfering RNAs (siRNAs) in vitro. Here we report the 2.5 A crystal structure of
      p19 from the Carnation Italian ringspot virus (CIRV) bound to a 21 nt siRNA and
      demonstrate in biochemical and in vivo assays that CIRV p19 protein acts as a
      molecular caliper to specifically select siRNAs based on the length of the duplex
      region of the RNA.

PMID- 14697200
TI  - Cell cycle regulated transport controlled by alterations in the nuclear pore
      complex.
AB  - Eukaryotic cells have developed mechanisms for regulating the nuclear transport
      of macromolecules that control various cellular events including movement through
      defined stages of the cell cycle. In yeast cells, where the nuclear envelope
      remains intact throughout the cell cycle, these transport regulatory mechanisms
      must also function during mitosis. We have uncovered a mechanism for regulating
      transport that is controlled by M phase specific molecular rearrangements in the
      nuclear pore complex (NPC). These changes allow a transport inhibitory
      nucleoporin, Nup53p, to bind the karyopherin Kap121p specifically during mitosis,
      slowing its movement through the NPC and inducing cargo release. Yeast strains
      that possess defects in the function of Kap121p or the fidelity of the inhibitory
      pathway are delayed in mitosis. We propose that fluctuations in Kap121p transport
      mediated by the NPC contribute to controlling the subcellular distribution of
      molecules that direct progression through mitosis.

PMID- 14697202
TI  - An intrinsic adenylate kinase activity regulates gating of the ABC transporter
      CFTR.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel in
      the ATP binding cassette (ABC) transporter family. Like other ABC transporters,
      it can hydrolyze ATP. Yet while ATP hydrolysis influences channel gating, it has
      long seemed puzzling that CFTR would require this reaction because anions flow
      passively through CFTR. Moreover, no other ion channel is known to require the
      large energy of ATP hydrolysis to gate. We found that CFTR also has adenylate
      kinase activity (ATP + AMP <=> ADP + ADP) that regulates gating. When functioning
      as an adenylate kinase, CFTR showed positive cooperativity for ATP suggesting its
      two nucleotide binding domains may dimerize. Thus, channel activity could be
      regulated by two different enzymatic reactions, ATPase and adenylate kinase, that
      share a common ATP binding site in the second nucleotide binding domain. At
      physiologic nucleotide concentrations, adenylate kinase activity, rather than
      ATPase activity may control gating, and therefore involve little energy
      consumption.

PMID- 14697201
TI  - The C. elegans hook protein, ZYG-12, mediates the essential attachment between
      the centrosome and nucleus.
AB  - The centrosome and nucleus are intimately associated in most animal cells, yet
      the significance of this interaction is unknown. Mutations in the zyg-12 gene of
      Caenorhabditis elegans perturb the attachment of the centrosome to the nucleus,
      giving rise to aberrant spindles and ultimately, DNA segregation defects and
      lethality. These phenotypes indicate that the attachment is essential. ZYG-12 is
      a member of the Hook family of cytoskeletal linker proteins and localizes to both
      the nuclear envelope (via SUN-1) and centrosomes. ZYG-12 is able to bind the
      dynein subunit DLI-1 in a two-hybrid assay and is required for dynein
      localization to the nuclear envelope. Loss of dynein function causes a low
      percentage of defective centrosome/nuclei interactions in both Drosophila and
      Caenorhabditis elegans. We propose that dynein and ZYG-12 move the centrosomes
      toward the nucleus, followed by a ZYG-12/SUN-1-dependent anchorage.

PMID- 14697203
TI  - Serotonylation of small GTPases is a signal transduction pathway that triggers
      platelet alpha-granule release.
AB  - Serotonin is a neurotransmitter in the central nervous system. In the periphery,
      serotonin functions as a ubiquitous hormone involved in vasoconstriction and
      platelet function. Serotonin is synthesized independently in peripheral tissues
      and neurons by two different rate-limiting tryptophan hydroxylase (TPH)
      isoenzymes. Here, we show that mice selectively deficient in peripheral TPH and
      serotonin exhibit impaired hemostasis, resulting in a reduced risk of thrombosis
      and thromboembolism, although the ultrastructure of the platelets is not
      affected. While the aggregation of serotonin-deficient platelets in vitro is
      apparently normal, their adhesion in vivo is reduced due to a blunted secretion
      of adhesive alpha-granular proteins. In elucidating the mechanism further, we
      demonstrate that serotonin is transamidated to small GTPases by transglutaminases
      during activation and aggregation of platelets, rendering these GTPases
      constitutively active. Our data provides evidence for a receptor-independent
      signaling mechanism, termed herein as "serotonylation," which leads to alpha
      granule exocytosis from platelets.

PMID- 14697204
TI  - A key role for TRPM7 channels in anoxic neuronal death.
AB  - Excitotoxicity in brain ischemia triggers neuronal death and neurological
      disability, and yet these are not prevented by antiexcitotoxic therapy (AET) in
      humans. Here, we show that in neurons subjected to prolonged oxygen glucose
      deprivation (OGD), AET unmasks a dominant death mechanism perpetuated by a Ca2+
      permeable nonselective cation conductance (IOGD). IOGD was activated by reactive
      oxygen/nitrogen species (ROS), and permitted neuronal Ca2+ overload and further
      ROS production despite AET. IOGD currents corresponded to those evoked in HEK-293
      cells expressing the nonselective cation conductance TRPM7. In cortical neurons,
      blocking IOGD or suppressing TRPM7 expression blocked TRPM7 currents, anoxic
      45Ca2+ uptake, ROS production, and anoxic death. TRPM7 suppression eliminated the
      need for AET to rescue anoxic neurons and permitted the survival of neurons
      previously destined to die from prolonged anoxia. Thus, excitotoxicity is a
      subset of a greater overall anoxic cell death mechanism, in which TRPM7 channels
      play a key role.

PMID- 14697205
TI  - A neuronal isoform of the aplysia CPEB has prion-like properties.
AB  - Prion proteins have the unusual capacity to fold into two functionally distinct
      conformations, one of which is self-perpetuating. When yeast prion proteins
      switch state, they produce heritable phenotypes. We report prion-like properties
      in a neuronal member of the CPEB family (cytoplasmic polyadenylation element
      binding protein), which regulates mRNA translation. Compared to other CPEB family
      members, the neuronal protein has an N-terminal extension that shares
      characteristics of yeast prion-determinants: a high glutamine content and
      predicted conformational flexibility. When fused to a reporter protein in yeast,
      this region confers upon it the epigenetic changes in state that characterize
      yeast prions. Full-length CPEB undergoes similar changes, but surprisingly it is
      the dominant, self-perpetuating prion-like form that has the greatest capacity to
      stimulate translation of CPEB-regulated mRNA. We hypothesize that conversion of
      CPEB to a prion-like state in stimulated synapses helps to maintain long-term
      synaptic changes associated with memory storage.

PMID- 14697207
TI  - A cell-based model of coagulation and the role of factor VIIa.
AB  - Our cell-based model of haemostasis replaces the traditional 'cascade'
      hypothesis, and proposes that coagulation takes place on different cell surfaces
      in three overlapping steps: initiation, amplification, and propagation. In
      highlighting the importance of cellular control during coagulation, the cell
      based model allows a more thorough understanding of how haemostasis works in
      vivo, and sheds light on the pathophysiological mechanisms behind certain
      coagulation disorders. For instance, this model proposes that haemophilia
      involves a failure of platelet-surface FXa generation, leading to a lack of
      platelet-surface thrombin production. Our data suggest that high-dose FVIIa is
      able to bind weakly to activated platelets, independently of tissue factor, in
      order to generate sufficient amounts of FXa to support a burst bf thrombin
      generation in the absence of FIXa/FVIIIa. The considerable success of high-dose
      recombinant FVIIa (rFVIIa; NovoSeven, Novo Nordisk, Copenhagen, Denmark) as a
      therapy for patients with haemophilia and inhibitors has led to its use in a
      growing number of alternative indications. We believe that even in the presence
      of the FIXa/FVIIIa complex, rFVIIa may be able to enhance both FXa and FIXa
      levels on the surface of activated platelets, thus increasing the production of
      thrombin.

PMID- 14697206
TI  - A neuronal isoform of CPEB regulates local protein synthesis and stabilizes
      synapse-specific long-term facilitation in aplysia.
AB  - Synapse-specific facilitation requires rapamycin-dependent local protein
      synthesis at the activated synapse. In Aplysia, rapamycin-dependent local protein
      synthesis serves two functions: (1) it provides a component of the mark at the
      activated synapse and thereby confers synapse specificity and (2) it stabilizes
      the synaptic growth associated with long-term facilitation. Here we report that a
      neuron-specific isoform of cytoplasmic polyadenylation element binding protein
      (CPEB) regulates this synaptic protein synthesis in an activity-dependent manner.
      Aplysia CPEB protein is upregulated locally at activated synapses, and it is
      needed not for the initiation but for the stable maintenance of long-term
      facilitation. We suggest that Aplysia CPEB is one of the stabilizing components
      of the synaptic mark.

PMID- 14697208
TI  - Haemopoietic stem cell transplants: the impact of haemorrhagic complications.
AB  - Acute graft-versus-host disease (GVHD) is the most important complication of
      allogeneic haemopoietic stem cell transplantation (HSCT), increasing
      susceptibility to haemorrhage and risk of early mortality. We evaluated 807
      allogeneic HSCT patients to assess both the association between bleeding and
      GVHD, and the influence of haemorrhagic complications on clinical outcome. Up to
      55% of patients with grade III-IV GVHD experienced bleeding, compared with 23% of
      patients with grades 0-l. Furthermore, 45% of patients receiving non-HLA
      identical transplants suffered haemorrhage, whereas only 23% of patients
      receiving transplants from HLA-identical donors experienced bleeding. This can be
      explained by the higher incidence of severe GVHD among recipients of non-HLA
      identical transplants. Our findings also demonstrated that haemorrhagic
      complications--particularly bleeding from the GI tract--markedly increase patient
      mortality. An ongoing, multi-centre, randomised, double-blind trial is currently
      investigating the efficacy and safety of recombinant factor VIIa (rFVIIa;
      NovoSeven) in the treatment of HSCT-associated bleeding. The trial will examine
      the ability of three dose levels of rFVIIa to reduce--or even eliminate entirely-
      the incidence and severity of haemorrhage following such procedures. A total
      enrollment of 100 patients is anticipated, and preliminary data are expected at
      the end of 2003.

PMID- 14697209
TI  - Recombinant factor VIIa (rFVIIa) and its use in severe bleeding in surgery and
      trauma: a review.
AB  - Haemorrhage is a potential complication of any surgical procedure, presenting a
      major challenge to the surgeon and anaesthetist. In addition, uncontrolled
      bleeding accounts for at least 40% of the mortality associated with military and
      civilian trauma. Despite the widespread availability of standard interventions
      for the control of bleeding in such circumstances, there still remains an urgent
      need for an effective haemostatic agent that is safe, easy to use, and able to
      enhance local thrombotic processes without causing generalised arterial or venous
      thrombosis. Recombinant factor VIIa (rFVIIa; NovoSeven) has been successfully
      used in the management of haemophilia patients with inhibitors for many years.
      This review will explore its use in the control of surgery- and trauma-associated
      haemorrhage in patients without pre-existing coagulopathy, and will highlight the
      growing realisation that rFVIIa may have a major role not only as a treatment for
      haemophilia, but also as a universal haemostatic agent. This paper will also
      briefly explore those unanswered questions that should be resolved by future
      trials aiming to further clarify the safety, efficacy, and optimal dosing
      strategies of rFVIIa in the surgical and trauma settings.

PMID- 14697210
TI  - Cancer metabolism: facts, fantasy, and fiction.
AB  - The concept of a glycolytic cancer cell was introduced by Warburg over 70 years
      ago. This perception has since become the rationale that drives a considerable
      proportion of basic research on cancer, and it influences the current strategies
      for the diagnosis, monitoring, and treatment of cancer. Here we review the data
      from the last 40 years on this issue. We conclude that there is no evidence that
      cancer cells are inherently glycolytic, but that some tumours might indeed be
      glycolytic in vivo as a result of their hypoxic environment.

PMID- 14697211
TI  - Purification and crystallization of haemoglobin from donkey (Equus asinus).
AB  - Haemoglobin acts as an important protein for oxygen carrier in all living beings.
      Purification of donkey haemoglobin was done using PEG 4000 as a separating
      medium. Crystallization was achieved using hanging drop vapor diffusion method
      using 2.8 M phosphate buffer, pH 6.8. Data collection was done using mar345 image
      plate detector system. The crystals grown under 2.8 M phosphate buffer are
      monoclinic with space group C2 and cell dimensions a=107.664 A, b=63.084 A,
      c=54.042 A, and beta=111.747 degrees.

PMID- 14697212
TI  - FBP11 regulates nuclear localization of N-WASP and inhibits N-WASP-dependent
      microspike formation.
AB  - WASP family proteins are involved in cortical actin cytoskeleton reorganization.
      Neural Wiskott-Aldrich syndrome protein (N-WASP), a ubiquitously expressed WASP
      homologous protein, directly binds with Cdc42, activating Arp2/3 complex. In this
      study, we show that N-WASP-dependent microspike formation is inhibited by formin
      binding protein 11 (FBP11). Endogenous FBP11 localizes with nuclear-speckles, and
      co-localization of N-WASP and FBP11 was observed when they were co-expressed.
      Epidermal growth factor (EGF) induced actin-microspike formation in COS7 cells.
      However, transient expression of FBP11 suppressed N-WASP-dependent actin
      microspike formation by trapping N-WASP in the nucleus. These results indicate
      that FBP11 regulates localization of N-WASP, thus negatively regulating the
      function of N-WASP in the cytoplasm.

PMID- 14697213
TI  - Involvement of Ras in extraembryonic endoderm differentiation of embryonic stem
      cells.
AB  - Embryonic stem (ES) cells, derived from the inner cell mass of blastocyst can
      differentiate into multiple cell lineages. In this study, we examined the
      possible involvement of Ras in ES cell differentiation. We found that Ras was
      activated upon formation of embryoid bodies (EBs), an initial step in ES cell
      differentiation. When expressed during EB differentiation, a dominant-negative
      mutant of Ras suppressed induction of marker genes for extraembryonic endoderm
      differentiation, including GATA-4, GATA-6, alpha-fetoprotein, and hepatocyte
      nuclear factor 3beta, while an activated mutant promoted their induction.
      Expression of a Ras mutant that selectively activates the Raf/MEK/Erk pathway
      also enhanced induction of extraembryonic endoderm markers, and treatment with a
      MEK inhibitor resulted in their decreased expression. In addition, Ras stimulated
      downregulation of Nanog, a suppressor of endoderm differentiation in ES cells.
      These data suggest that Ras activation during EB differentiation plays a crucial
      role in initiation of extraembryonic endoderm differentiation.

PMID- 14697214
TI  - A novel nuclear localization signal in the human single-minded proteins SIM1 and
      SIM2.
AB  - Human Single-minded 1 (SIM1) and SIM2 genes were found as homologs of Drosophila
      sim gene which plays a key role in the midline cell lineage of the central
      nervous system. SIM proteins belong to a family of transcription factors, called
      bHLH/PAS. Here we examined the intracellular localization of SIM proteins using
      the expression constructs of whole SIM2 or SIM1 protein fused with enhanced green
      fluorescent protein (EGFP). The transient expression analysis revealed the
      nuclear localization of SIM proteins in the cultured cells. To identify the
      nuclear localization signal, we made expression constructs of EGFP-fusion protein
      consisting of various portions of SIM proteins. Transfection assay showed the
      presence of NLS activity in the small region of 23 and 21 amino acid residues at
      the central part of SIM2 and SIM1 proteins, respectively. Further analysis with
      amino acid substitution of this small region of SIM2 protein revealed the
      critical role of five amino acid residues (Arg367, Lys373, Pro385, Tyr386, and
      Gln389) in NLS activity. The consensus sequence of RKxxKx[K/R]xxxxKxKxRxxPY was
      estimated as a presumptive NLS in SIM proteins from various species. Thus, the
      NLS consisting of a cluster of basic amino acids with Pro and Tyr at the C
      terminal end is novel and well conserved in the SIM proteins during evolution.

PMID- 14697215
TI  - Two distinct methods analyzing chromatin structure using centrifugation and
      antibodies to modified histone H3: both provide similar chromatin states of the
      Rit1/Bcl11b gene.
AB  - Chromatin state of a 2-Mb region harboring Rit1/Bcl11b on mouse chromosome 12 was
      examined using two distinct methods. One is ChIP assay examining the degree of
      enrichment with histone H3 methylated at lysine 9 (H3-mLys9) in chromatin and the
      other is H/E (heterochromatin/euchromatin) assay that measures a chromatin
      condensation state by using centrifugation. The ChIP assay showed that a 50-kb
      interval covering the gene and an upstream region constituted chromatin enriched
      with unmethylated H3-mLys9 in cells expressing Rit1 compared to cells not
      expressing Rit1. In contrast, regions other than the 50-kb interval did not show
      much difference in the enrichment between the two different types of cells. On
      the other hand, H/E assay of two expressing and two non-expressing tissues
      provided compatible fractionation patterns, suggesting that the chromatin
      condensation state detected by H/E assay is correlated with the chromatin state
      controlled by histone H3 tail modification linked to gene expression. These
      results indicate that the centrifugation-based H/E assay should provide a new
      approach to the regulation of chromatin structure with respect to its
      condensation state, complementing ChIP assays.

PMID- 14697216
TI  - Tyrosine-728 and glutamic acid-735 are essential for the metalloproteolytic
      activity of the lethal factor of Bacillus anthracis.
AB  - The lethal factor (LF) of Bacillus anthracis is a Zn2+-endopeptidase specific for
      the MAPK-kinase family of proteins. The catalytic zinc atom is coordinated by a
      first shell of residues including the two histidines and the glutamate of the
      zinc-binding motif HExxH and by Glu-735. A characteristic feature of LF is the
      presence, within the second shell of residues, of a tyrosine (Tyr-728) in close
      proximity (3.3 A) to the zinc atom. To investigate the role of Tyr-728 and Glu
      735, LF mutants with one or both of these two residues replaced by Ala were
      cloned, expressed, and purified from Escherichia coli. A fourth mutant was
      obtained by replacing Tyr-728 with Phe. Spectroscopic analysis of these mutants
      indicates that they fold in the same way as the parental molecule and that zinc
      stabilizes the structure of LF. These mutants have neither proteolytic activity
      nor in vivo toxicity. The possible role of Tyr-728 in catalysis is discussed.

PMID- 14697218
TI  - Trigger factor-assisted folding of bovine carbonic anhydrase II.
AB  - Spontaneous refolding of GdnHCl denatured bovine carbonic anhydrase II (BCA II)
      shows at least three phases: a burst phase, a fast phase, and a slow phase. The
      fast and slow phases are both controlled by proline isomerization. However, we
      find that in trigger factor (TF)-assisted BCA II folding, only the fast phase is
      catalyzed by wild-type TF, suggesting that certain proline residues are
      accessible in folding intermediates. The refolding yields of BCA II assisted by
      wild-type TF and TF mutants which lack PPIase activity are about the same, which
      provides further experimental evidence that the PPIase and chaperone activities
      of TF are independent. The binding of TF to folding intermediates during BCA II
      refolding was characterized by chemical crosslinking and Western blotting. A
      scheme for TF-assisted BCA II folding is proposed and the possible role of the TF
      dimer as a "binding" chaperone in vivo is discussed.

PMID- 14697217
TI  - A new technique to expand human mesenchymal stem cells using basement membrane
      extracellular matrix.
AB  - Mesenchymal stem cells (MSC) show a very short proliferative life span and
      readily lose the differentiation potential in culture. However, the growth rate
      and the proliferative life span of the stem cells markedly increased using tissue
      culture dishes coated with a basement membrane-like extracellular matrix, which
      was produced by PYS-2 cells or primary endothelial cells. Furthermore, the stem
      cells expanded on the extracellular matrix, but not those on plastic tissue
      culture dishes, retained the osteogenic, chondrogenic, and adipogenic potential
      throughout many mitotic divisions. The extracellular matrix had greater effects
      on the proliferation of MSC and the maintenance of the multi-lineage
      differentiation potential than basic fibroblast growth factor. Mesenchymal stem
      cells expanded on the extracellular matrix should be useful for regeneration of
      large tissue defects and repeated cell therapies, which require a large number of
      stem or progenitor cells.

PMID- 14697219
TI  - Overproduction of PU.1 in mast cell progenitors: its effect on monocyte- and mast
      cell-specific gene expression.
AB  - The Ets family transcription factor PU.1 is required for development of various
      lymphoid and myeloid cell lineages, and regulates the expression of several genes
      in a cell type-specific manner. Mouse bone marrow-derived hematopoietic
      progenitor cells are programmed to differentiate into mast cells, when the cells
      are maintained in the presence of pokeweed mitogen-stimulated spleen-conditioned
      medium. However, by retroviral introduction of PU.1 cDNA, the progenitor cells
      expressed MHC class II, CD11b, CD11c, and F4/80, and acquired the ability to
      stimulate T cells. Furthermore, PU.1-overproducing cells exhibited the
      morphology, in part, similar to that of monocyte. These results indicate that the
      mast cell progenitors still have the ability to express monocyte-specific genes
      by increased expression of PU.1.

PMID- 14697220
TI  - Transduction of anti-apoptotic proteins into chondrocytes in cartilage slice
      culture.
AB  - Peptides of the protein transduction domain (PTD) mediate the introduction of
      passenger proteins into cells in vitro and in vivo, where the domains are
      positively charged. This unusual ability can be exploited for medical
      applications in protein therapeutics. Chondrocytes are embedded in a dense
      extracellular matrix, whose components are highly negatively charged. We examined
      whether PTD mediates the delivery of functional proteins into chondrocytes
      through the matrix using the super anti-apoptotic protein FNK fused with Tat/PTD
      peptide (PTD-FNK), the FNK protein being constructed from anti-apoptotic Bcl-xL
      to enhance its activity. The PTD-FNK protein labeled with a fluorescent dye was
      incorporated into chondrocytes through the matrix and immunostaining confirmed
      the transduction into the cells. The PTD-FNK protein protected chondrocytes from
      cell death induced by Fas antibody and nitrogen oxide (NO). Thus, the PTD peptide
      has the ability to deliver passenger proteins into chondrocytes by penetrating
      the extracellular matrix of cartilage.

PMID- 14697221
TI  - Potential for germ line transmission after intramyocardial gene delivery by adeno
      associated virus.
AB  - Intramyocardial injection of adeno-associated virus (AAV) has been shown to be an
      effective strategy for cardiac gene delivery. This approach leads to long-term
      gene expression in the heart, offering the possibility of chronic gene therapy.
      However, the long-term safety of this approach with regard to vector bio
      distribution and extracardiac transgene expression has not been evaluated. To
      examine these issues, 8-week-old male Sprague-Dawley rats were injected
      intramyocardially with either 4x10(11) particles of AAV-2-lacZ or saline at five
      locations in the anterioposterior apical region of the left ventricle. Animals
      were sacrificed at 3 and 6 months after gene transfer, tissues were harvested and
      analyzed for lacZ expression by semi-quantitative RT-PCR and beta-galactosidase
      activity using X-gal staining. We observed high level of transgene expression in
      the myocardium at 3 months after gene transfer, which persisted up to 6 months of
      follow-up. Also, significantly we detected lacZ expression and beta-galactosidase
      activity in extracardiac tissues such as liver, kidney, and testes at 6 months.
      More significantly, late transgene expression was detected in cellular elements
      of the seminiferous tubule, including Sertoli cells and spermatogonia like cells.
      These data demonstrate the efficacy of AAV-2 delivery for long-term myocardial
      gene therapy, but raise concerns about the possibility of ectopic transgene
      expression and germ cell line infection.

PMID- 14697222
TI  - Human apolipoprotein(a) kringle V inhibits angiogenesis in vitro and in vivo by
      interfering with the activation of focal adhesion kinases.
AB  - Apolipoprotein(a) [apo(a)] contains the largest numbers of kringle domains
      identified to date. Of these, apo(a) kringle V shows significant sequence
      homology with plasminogen kringle 5, which is reported to be a potent
      angiogenesis inhibitor. To determine the effects of apo(a) kringle V on
      angiogenesis, it was expressed as a soluble protein (termed rhLK8) in Pichia
      pastoris and its in vitro and in vivo anti-angiogenic properties were examined.
      rhLK8 inhibited the migration of human umbilical vein endothelial cells in vitro
      in a dose-dependent manner. This function was associated with the down-regulation
      of the activation of focal adhesion kinase and the inhibition of the consequent
      formation of actin stress fibers/focal adhesions. rhLK8 also inhibited new
      capillary formation in vivo, as assessed by the chick chorioallantoic membrane
      assay and the Matrigel plug assay. These results indicate that rhLK8 may be an
      effective angiogenesis inhibitor both in vitro and in vivo.

PMID- 14697223
TI  - Evaluation of penicillin-based inhibitors of the class A and B beta-lactamases
      from Bacillus anthracis.
AB  - Bacillus anthracis contains a class A (Bla1) and class B (Bla2) beta-lactamase,
      which confer resistance to beta-lactam antibiotics when expressed in Escherichia
      coli. In an effort to find new beta-lactamase inhibitors, several penicillin
      derivatives have been evaluated including experimental compounds incorporating a
      6-mercaptomethyl group or a 6-pyridylmethylidene group, along with clavulanate
      and tazobactam, as inhibitors against Bla1 and Bla2. The 6-mercaptomethyl
      substituted penicillins showed much greater activity against the zinc-containing
      Bla2 than Bla1. The compound that incorporated a 6-pyridylmethylidene substituent
      and a catecholic substituent at the 2' position was the most effective inhibitor
      of Bla1 with Ki=0.057 microM. Inhibitors containing iron-chelating functional
      groups have previously been shown to work in combination with antibiotics to
      inhibit growth of antibiotic-resistant bacteria expressing beta-lactamase. The
      development of similar compounds, incorporating these types of substituents, may
      help overcome resistance to currently used antibiotics.

PMID- 14697224
TI  - Cirrhotic hepatocytes exhibit decreased TGFbeta growth inhibition associated with
      downregulated Smad protein expression.
AB  - TGFbeta controls hepatocyte growth through cell cycle arrest and apoptosis, and
      resistance to TGFbeta is a mechanism of malignant transformation. The aim of this
      study was to assess differences in TGFbeta-mediated growth inhibition in normal
      and cirrhotic hepatocytes. Cirrhosis was induced in mice and normal and cirrhotic
      hepatocytes were isolated by collagenase perfusion and treated with or without
      TGFbeta (5 ng/ml). DNA synthesis, Smad protein expression, and DNA binding
      activity were determined. TGFbeta reduced DNA synthesis to a greater degree in
      normal hepatocytes than in cirrhotic hepatocytes (87% vs. 68%; p<0.05). Smad
      protein expression was decreased in cirrhotic hepatocytes and Smad 2/3/4 complex
      formation was suppressed. Furthermore, cirrhotic hepatocytes had decreased DNA
      binding activity at 120 min following TGFbeta treatment. In conclusion, decreased
      Smad protein expression may impair TGFbeta-mediated growth inhibition in
      cirrhotic hepatocytes.

PMID- 14697225
TI  - Defective RNA-mediated c-myc gene silencing pathway in Burkitt's lymphoma.
AB  - Keeping in view the fact that molecular basis of Burkitt's lymphoma (BL) is
      poorly understood, we attempted to explore the small interfering RNA (siRNA)
      mediated c-myc gene regulation using BL-derived EB-3 cell line as archetype
      cellular model. Such a study revealed that EB-3 cells possess 4-fold higher
      expression of Dicer gene coupled with 2-fold higher activity of RNA polymerase
      III than that observed in normal human lymphocytes. siRNAs derived from EB-3
      cells had the inherent capacity to suppress c-myc gene expression in normal cells
      but not in native cells. Based on these findings we have proposed a novel RNA
      mediated c-myc gene regulation pathway that may be responsible for BL.

PMID- 14697226
TI  - Affinity labeled glutaryl-7-amino cephalosporanic acid acylase C130 can hydrolyze
      the inhibitor during crystallization.
AB  - 7Beta-bromoacetyl amino cephalosporanic acid (BA-7-ACA), an analog of glutaryl-7
      amino cephalosporanic acid (GL-7-ACA), can inhibit and specifically alkylate GL-7
      ACA acylase (C130) from Pseudomonas sp.130, forming a carbon-carbon bond between
      BA-7-ACA and the C-2 on indole ring of Trp-beta4 residue of C130. Here we
      reported that BA-7-ACA labeled C130 (BA-C130) could self-catalyze the hydrolysis
      of BA-7-ACA during crystallization process. The hydrolysis was confirmed to be a
      reaction analogous to the one of GL-7-ACA by comparative matrix-assisted laser
      desorption/ionization-time of flight (MALDI-TOF) spectrometry analysis. BA-C130
      was inactive at room temperature, but in the process of crystallization at 18
      degrees C it catalyzed the hydrolysis of BA-7-ACA, and thus made the latter
      become a substrate. Meanwhile, in crystals, 7-ACA was released but the acetic
      acid still bound with Trp-beta4, and as a result, the enzyme remained to be
      inactive. These results demonstrated that Trp-beta4 in the alphabetabetaalpha
      motif was critical and sensitive for the activity of C130 and also suggested that
      there was a conformational change induced by deacylation during the process of
      crystallization.

PMID- 14697227
TI  - Binding of prion proteins to lipid membranes.
AB  - A key molecular event in prion diseases is the conversion of the normal cellular
      form of the prion protein (PrPC) to an aberrant form known as the scrapie
      isoform, PrPSc. Under normal physiological conditions PrPC is attached to the
      outer leaflet of the plasma membrane via a GPI-anchor. It has been proposed that
      a direct interaction between PrP and lipid membranes could be involved in the
      conversion of PrPC to its disease-associated corrupted conformation, PrPSc.
      Recombinant PrP can be refolded into an alpha-helical structure, designated alpha
      PrP isoform, or into beta-sheet-rich states, designated beta-PrP isoform. The
      current study investigates the binding of recombinant PrP isoforms to model lipid
      membranes using surface plasmon resonance spectroscopy. The binding of alpha- and
      beta-PrP to negatively charged lipid membranes of POPG, zwitterionic membranes of
      DPPC, and model raft membranes composed of DPPC, cholesterol, and sphingomyelin
      is compared at pH 7 and 5, to simulate the environment at the plasma membrane and
      within endosomes, respectively. It is found that PrP binds strongly to lipid
      membranes. The strength of the association of PrP with lipid membranes depends on
      the protein conformation and pH, and involves both hydrophobic and electrostatic
      lipid-protein interactions. Competition binding measurements established that the
      binding of alpha-PrP to lipid membranes follows a decreasing order of affinity to
      POPG>DPPC>rafts.

PMID- 14697228
TI  - Alterations in blood pressure due to chronic exposure to natural sour gas leakage
      containing sulfur compounds.
AB  - In order to show the alteration of blood pressure in subjects chronically exposed
      to natural gas containing sulfur compounds, the present study was done. The blood
      pressure of 94 (43 males, 51 females) of healthy individuals living in the
      polluted area of Masjid-i-Sulaiman (Khozestan province, southwest of Iran) was
      measured. The non-parametric Sign test was applied in order to detect differences
      between the study subjects and the normal mean values according to the sex and
      age of subjects. Statistical analysis showed that the systolic blood pressure
      significantly decreased (Z=-2.74; P=0.0031) while the diastolic blood pressure
      (Z=+2.11; P=0.0174) and heart rate (Z=+3.62; P<0.001) significantly increased in
      individuals living in the contaminated areas compared with those of normal mean
      values. The systolic and diastolic blood pressure decreased and increased,
      respectively, in individuals chronically exposed to natural sour gas containing
      sulfur compounds.

PMID- 14697229
TI  - Cloning of a gene encoding flavin reductase coupling with dibenzothiophene
      monooxygenase through coexpression screening using indigo production as selective
      indication.
AB  - The thermophilic dibenzothiophene (DBT)-desulfurizing bacterium, Bacillus
      subtilis WU-S2B, possesses the ability to convert DBT to 2-hydroxybiphenyl with
      the release of inorganic sulfur over a wide temperature range up to 50 degrees C.
      The conversion is initiated by consecutive sulfur atom-specific oxidations by two
      monooxygenases, and flavin reductase is essential in combination with these
      flavin-dependent monooxygenases. The recombinant Escherichia coli cells
      expressing the DBT monooxygenase gene (bdsC) from B. subtilis WU-S2B also oxidize
      indole to blue pigment indigo in the presence of a heterologous flavin reductase.
      Thus, to clone a gene encoding flavin reductase from B. subtilis WU-S2B, indigo
      production by coexpression of the gene with bdsC in E. coli was used as a
      selection. Using this method, the corresponding gene (frb) was obtained from a
      recombinant strain forming a blue colony due to indigo production on a nutrient
      agar plate, and it was confirmed that this gene product Frb exhibited flavin
      reductase activity. The deduced amino acid sequence of frb consists of 174 amino
      acid residues and shares 61% identity with that of nitroreductase (YwrO) of
      Bacillus amyloliquefaciens. In addition, coexpression of frb with the DBT
      desulfurization genes (bdsABC) from B. subtilis WU-S2B was critical for high DBT
      desulfurizing ability over a wide temperature range of 20-55 degrees C. This
      coexpression screening using indigo production as selective indication may be
      widely applicable for cloning novel genes encoding either component of flavin
      reductase or flavin-dependent monooxygenase which efficiently couples with the
      other component in two-component monooxygenases.

PMID- 14697230
TI  - Chromosome positional effects of gene expressions after cellular senescence.
AB  - Normal human fibroblasts stop dividing after a limited number of cell divisions
      termed cellular senescence. Telomere shortening has been shown to be the main
      factor that causes cellular senescence, however, the molecular mechanism of how
      telomere shortening causes cellular senescence is unclear. Here we analyze the
      relationship between gene expressions and their chromosomal locations during
      cellular senescence. It appears that the expression of genes located in
      chromosome 4 is preferentially altered after senescence. Moreover, we identify
      four chromosomal loci in which gene expressions are affected by senescence.
      Finally, we show that there is no preferential alteration of telomere-proximal
      genes during cellular senescence, implying that cellular senescence is not caused
      by derepression of telomere-proximal genes.

PMID- 14697231
TI  - Perturbation of ATP-induced tetramerization of human cytosolic thymidine kinase
      by substitution of serine-13 with aspartic acid at the mitotic phosphorylation
      site.
AB  - Human cytosolic thymidine kinase (TK1) is tightly regulated in the cell cycle by
      multiple mechanisms. Our laboratory has previously shown that in mitotic-arrested
      cells human TK1 is phosphorylated at serine-13, accompanied by a decrease in
      catalytic efficiency. In this study we investigated whether serine-13
      phosphorylation regulated TK1 activity and found that substitution of serine-13
      with aspartic acid (S13D), which mimics phosphorylation, not only diminished the
      ATP-activating effect on the enzyme, but also decreased its thymidine substrate
      affinity. Our experimental results further showed that the S13D mutation
      perturbed ATP-induced tetramerization of TK1. Given that the dimeric form of TK1
      is less active than the tetrameric, we propose that mitotic phosphorylation of
      serine-13 is of physiological importance, in that it may counteract ATP-dependent
      activation of TK1 by affecting its quaternary structure, thus attenuating its
      enzymatic function at the G2/M phase.

PMID- 14697232
TI  - Increased expression and activity of 11beta-HSD-1 in diabetic islets and
      prevention with troglitazone.
AB  - To determine if increased local production of glucocorticoids by the pancreatic
      islets might play a role in the spontaneous noninsulin-dependent diabetes
      mellitus of obesity, we compared islet 11beta-HSD-1 mRNA and activity in islets
      of obese prediabetic and diabetic Zucker Diabetic Fatty (ZDF) (fa/fa) rats and
      lean wild-type (+/+) controls. In diabetic rat islets, both mRNA and enzymatic
      activity of the enzyme were increased in proportion to the hyperglycemia.
      Troglitazone (TGZ) treatment, beginning at 6 weeks of age, prevented the
      hyperglycemia, the hyperlipidemia, and the increase in 11beta-HSD-1. To determine
      if the metabolic abnormalities had caused the 11beta-HSD-1 increase, prediabetic
      islets were cultured in high or low glucose or in 2:1 oleate:palmitate for 3
      days. Neither nutrient enhanced the expression of 11beta-HSD-1. We conclude that
      11beta-HSD-1 expression and activity are increased in islets of diabetic, but not
      prediabetic ZDF rats, and that TGZ prevents both the increase in 11beta-HSD-1 and
      the diabetes.

PMID- 14697233
TI  - SREBP contributes to induction of collagen VI transcription by serum starvation.
AB  - Collagen VI is a main extracellular matrix protein whose mutation is linked to
      myopathic diseases. In myoblasts and other cell types, collagen VI gene
      transcription peaks during cell-cycle exit that precedes differentiation, upon
      serum withdrawal or confluence. To get insight into this transcriptional
      regulation, we characterized a growth arrest responsive region (GARR) in the
      Col6a1 promoter responsible for this effect. In this work, we identify sterol
      regulatory element binding protein (SREBP) as a GARR binding protein and provide
      evidence that SREBP contributes to induction of Col6a1 transcription in serum
      free conditions. Furthermore, our data unveil a previously unexpected link
      between extracellular matrix production and LDL signaling.

PMID- 14697234
TI  - Soluble HLA-G generated by proteolytic shedding inhibits NK-mediated cell lysis.
AB  - In contrast to the classical HLA class Ia molecules, the nonclassical HLA-G
      primary transcript is alternatively spliced to generate several mRNAs that encode
      four membrane-bound and three soluble isoforms. This study demonstrated that the
      soluble form of HLA-G can also be generated by metalloproteinase-dependent
      shedding at post-translational level. These soluble HLA-G1 molecules generated by
      the cleavage of membrane-bound HLA-G1 associate with beta2-microglobulin and
      contain bound peptides that are stable at physiological conditions. This report
      further showed that the soluble HLA-G1 is able to protect HLA class I-negative
      K562 cells from NK lysis, suggesting that soluble HLA-G could act as an
      immunoregulator in NK cell recognition and possibly in other immune responses.

PMID- 14697235
TI  - SP3 acts as a positive regulator on the core promoter of human ZPK gene.
AB  - ZPK (zipper protein kinase)/MUK/DLK/MAP3K12, a member of mixed-lineage kinases
      (MLKs), is expressed in a tissue-specific manner, particularly in developing
      brain, and likely to contribute to cytodifferentiation, apoptotic elimination,
      and migration. To understand the preferential expression of ZPK in neuronal
      tissues, we have analyzed the putative core promoter region upstream of the first
      exon of the human ZPK gene. The core promoter region is TATA-less, but contains
      several potential transcription factor-binding motifs such as a GC-box, all of
      which are well conserved between human and mouse. Reporter assays and 'gel-shift'
      analysis using SH-SY5Y cells revealed that a xenobiotic responsive element (XRE)
      like motif (GGGCGTGTCC) was preferentially recognized by Sp3, and enhanced the
      core promoter activity. However, the core promoter activity was still potent even
      in HeLa cells which barely express ZPK. Our results suggest that, for the
      selective expression of ZPK gene, cell-specific negative regulatory element(s)
      which locate outside of the core promoter region repress the potent basic
      promoter activity.

PMID- 14697236
TI  - HuB localizes to polysomes and alters C/EBP-beta expression in 3T3-L1 adipocytes.
AB  - The RNA binding protein HuB was ectopically expressed in 3T3-L1 preadipocytes and
      localized primarily to the nucleus, as the cells differentiated HuB redistributed
      to the cytosol and on analysis localized to the dense polysomes. Electron
      micrographs confirm association of HuB with the ribosomes in the adipocytes
      consistent with a proposed role in control of translation and mRNA stability.
      Examination of the expression of C/EBP-beta in the cells expressing HuB relative
      to the parental 3T3-L1 adipocytes demonstrated an alteration in the LAP to LIP
      ratio. The data support a role for endogenous Hu proteins in the differentiation
      process, potentially affecting the rate of differentiation by controlling the
      concentration of the dominant negative transcription inhibitor, LIP.

PMID- 14697237
TI  - Central angiotensin II increases biosynthesis of tyrosine hydroxylase in the rat
      adrenal medulla.
AB  - Angiotensin II acting centrally contributes to the regulation of blood pressure
      and water intake and stimulates the release of catecholamines from the adrenal
      medulla. We hypothesized that the central angiotensin II is one mediator of
      biosynthesis of catecholamines in the adrenal medulla. Rats were administered
      i.c.v. angiotensin II or saline, and TH mRNA and protein levels in adrenal
      medulla were measured 1 or 3 h later. Angiotensin II did not change TH mRNA or
      protein 1 h later. However, by 3 h, angiotensin II increased TH mRNA and protein
      levels. Centrally administered angiotensin II elevates TH mRNA expression and
      protein levels in the adrenal medulla. In conclusion, one component of central
      angiotensin II elevation of blood pressure may be the result of increased
      catecholamine synthesis in the adrenal gland and elevated TH synthesis represents
      one underlying mechanism.

PMID- 14697238
TI  - Involvement of NF-kappaB in TGF-beta-mediated suppression of IL-4 signaling.
AB  - Control of immune response requires the coordinated integration of both
      stimulatory and inhibitory factors. Therefore, the cross-talk of different
      signaling pathways is critical in providing an integrated cellular response to
      multiple external signals. Both interleukin-4 (IL-4) and transforming growth
      factor (TGF-beta) are pleiotropic cytokines and play critical roles in
      controlling immune responses. For example, IL-4 mediates important pro
      inflammatory functions in asthma including induction of the IgE isotype switch
      and expression of vascular cell adhesion molecules. Whereas, TGF-beta is secreted
      from B, T, and dendritic cells as well as macrophages, and negatively regulates
      their proliferation, differentiation, and activation by other cytokines. In this
      study, we examined the effect of TGF-beta on IL-4 signaling using B cells as well
      as embryonic kidney cells. TGF-beta inhibited IL-4-induced IgG1 production and
      gene expression of germline epsilon transcripts in B cells. In embryonic kidney
      cells, TGF-beta signals suppressed IL-4-induced transcription, when we monitored
      using germline epsilon promoter DNA. Furthermore, activation of NF-kappaB
      resulted in a resistance to TGF-beta-mediated suppression of IL-4 signaling.
      These results indicate that TGF-beta-mediated regulation of IL-4 signaling may
      act by targeting NF-kappaB signaling.

PMID- 14697239
TI  - Differential role of the hippocampus, amygdala, and dorsal raphe nucleus in
      regulating feeding, memory, and anxiety-like behavioral responses to ghrelin.
AB  - Ghrelin is a peptide hormone produced and secreted from the stomach. Hypothalamic
      injection of the peptide increases food intake but it is not known if the peptide
      affects other brain regions. We measured several behavioral parameters such as
      anxiety (elevated plus maze), memory retention (step down test), and food intake
      after injections of different doses of the peptide in the hippocampus, amygdala,
      and dorsal raphe nucleus (DRN). The injection of ghrelin in the hippocampus and
      DRN significantly and dose dependently increased food intake in relation to
      controls rats, while injections into the amygdala did not affect the food intake.
      We also show for the first time that ghrelin clearly and dose dependently
      increases memory retention in the hippocampus, amygdala, and DRN. Moreover,
      ghrelin at different potencies induced anxiogenesis in these brain structures
      while the highest dose of 3 nmol/microl was effective in all of them. The
      comparison of sensitivity of each brain structure indicates a specific role of
      them for each of the behaviors studied. The results provide new insight in to the
      anatomical substrate and the functional role of extrahypothalamic ghrelin targets
      in the CNS.

PMID- 14697240
TI  - Dimerization of human recombinant resistin involves covalent and noncovalent
      interactions.
AB  - Resistin, an adipocyte secreted cysteine rich hormone has been implicated as
      molecular link between obesity and type 2 diabetes in a murine model. Although,
      at the protein level mouse and human resistin show remarkable similarities with
      respect to conserved cysteine residues, the physiological role of human resistin
      is not yet clear. In the present study we describe the purification and refolding
      of human recombinant resistin using two different refolding processes. Gel
      filtration analysis of protein refolded by both the methods revealed that human
      recombinant resistin, like mouse resistin, has a tendency to form dimers.
      Interestingly, dimerization of resistin appears to be mediated by both covalent
      (disulfide bond mediated) and non-covalent interactions as seen on reducing and
      non-reducing SDS-PAGE. Circular dichroism spectral analysis revealed that human
      resistin peptide backbone is a mixture of alpha-helical and beta-sheet
      conformation with significant amounts of unordered structure, similar to the
      mouse resistin. It is likely that the first cysteine (Cyst22) of human resistin,
      which is equivalent to mouse Cyst26, may be involved in stabilizing the dimers
      through covalent interaction.

PMID- 14697241
TI  - Pyridoxine 5'-phosphate oxidase is a candidate gene responsible for hypertension
      in Dahl-S rats.
AB  - To identify candidate genes responsible for hypertension in Dahl salt-sensitive
      rats (Dahl-S), an oligonucleotide microarray analysis was performed to find
      differentially expressed genes in kidneys of Dahl-S and Lewis rats. We obtained
      101 F2 male rats from Dahl-S and Lewis rats and performed precise measurements of
      blood pressure (BP) and heart rate by telemetric monitoring at 14 weeks of age
      after 9 weeks of salt-loading. The correlation analysis between genotypes of
      differentially expressed genes and BP in F2 rats indicated that pyridoxine 5'
      phosphate oxidase (Pnpo) and catecholamine-O-methyltransferease (Comt) showed a
      highly significant association with BP. However, in the case of Comt, the Dahl-S
      genotype correlated with low BP. Short/branched chain acyl-CoA dehydrogenase and
      Sah also showed a significant association with systolic blood pressure. The
      present study provided evidence that Pnpo is a candidate gene responsible for
      hypertension in Dahl-S rats.

PMID- 14697242
TI  - Chromosome 13q12 encoded Rho GTPase activating protein suppresses growth of
      breast carcinoma cells, and yeast two-hybrid screen shows its interaction with
      several proteins.
AB  - We have characterized the cDNA for a Rho GTPase activating protein (GAP) mapping
      to chromosome 13q12. The cDNA was characterized by determining the complete
      sequence of a 4.8 kb cDNA clone that represents the 5' untranslated region (UTR),
      the translated region, and the 3' UTR. The protein has a sterile alpha-motif
      (SAM), a distinct GAP domain, and a conserved START (StAR related lipid transfer)
      domain. The cDNA has 5 instability motifs (ATTTA) in the 3' UTR and one motif in
      the translated region between GAP and START domains. The RhoGAP transcript is
      truncated in some breast carcinoma cell lines and it has low expression in other
      breast cancer cell lines as compared to a normal breast cell line. We have
      previously observed the absence of RhoGAP transcript in a breast tumor specimen.
      A GST-fusion of the RhoGAP was tested for its specificity on RhoA, Cdc42, and
      Rac1. The protein was most active for RhoA. Transfection of RhoGAP into MCF7
      cells significantly inhibited cell growth. The introduction of the RhoGAP
      construct into MDAMB231 cells that had previously been transfected with a p21
      construct did not affect cell proliferation, indicating the involvement of p21 in
      Rho-mediated proliferation of cancer cells. NIH3T3 cells overexpressing RhoGAP
      showed considerable inhibition of stress fiber formation. Several cDNAs were
      identified as RhoGAP interactors by using the yeast two-hybrid assay system.
      These cDNAs correspond to SWI/SNF, alpha-tubulin, HMG CoA reductase, and TAX1
      binding protein (TAX1BP1). The interaction with HMG CoA reductase may partially
      explain the growth inhibition of breast carcinoma cells by statin class of
      cholesterol lowering drugs. The biological significance of the interacting
      proteins is discussed in the context of their involvement in tumorigenesis. Our
      results indicate that loss of RhoGAP or its altered activity suppresses the
      growth of breast tumor cells. The presence of various motifs in RhoGAP and its
      interaction with several other proteins suggest that the protein may regulate Rho
      signaling in multiple ways and possibly function in a Rho-independent manner.

PMID- 14697243
TI  - Pregnancy-associated changes in genome-wide gene expression profiles in the liver
      of cow throughout pregnancy.
AB  - The objective of the present study was to fabricate and use a bovine liver
      complementary DNA (cDNA) microarray to profile genome-wide gene expressions in
      the liver of cow throughout pregnancy. A cDNA library was prepared from liver
      total RNA collected from cows during estrous cycle and pregnancy, and from
      fetuses at different stages of pregnancy. The sequenced clones were compiled and
      annotated by basic local alignment search tool (BLASTn) and spotted onto glass
      slides. The annotated liver array represented 2675 genes. Of which, 1442 were
      known genes while 617 sequences had matches with sequences found in expressed
      sequence tags databases. In addition, 616 unknown sequences were found and these
      sequences may possibly be identified as candidates for novel bovine genes. For
      gene expression profiling studies, total RNA from livers of cows slaughtered on
      days 19, 27-28, 49-58, 150, and 245 of pregnancy (test RNAs) was separately
      reverse transcribed and labeled with either cyanine 5-fluorescent dye (Cy5) or
      Cy3. The test samples were individually compared with liver total RNA collected
      from nonpregnant cycling cows (control RNA) after reverse transcription and
      labeling with the opposite dye following a two-color hybridization method. After
      scanning, image acquisition, and normalization, genes that showed either more
      than 1.5-fold (test/control) induction or repression were selected for further
      analyses. Hierarchical clustering algorithm showed a clear induction of most
      liver genes on days 27-28 of pregnancy. Self-organizing maps algorithm identified
      groups of genes whose differential expression patterns were similar across
      pregnancy. In conclusion, we described fabrication of a bovine liver cDNA
      microarray, and demonstrate, for the first time, differential expression patterns
      of a large number of coregulated liver genes in parallel throughout pregnancy in
      the bovine.

PMID- 14697244
TI  - Characterization of a novel CI-976-sensitive lysophospholipid acyltransferase
      that is associated with the Golgi complex.
AB  - Recent studies have identified a novel lysophospholipid acyltransferase (LPAT)
      that is associated with the Golgi complex and that is sensitive to the previously
      characterized acyl-CoA cholesterol acyltransferase inhibitor, 2,2-methyl-N-(2,4,6
      trimethoxyphenyl)dodecanamide (CI-976). Here we show that besides acting on
      exogenous lysophospholipid (LPL) substrates, the CI-976-sensitive LPAT is also
      capable of reacylating endogenous Golgi LPL substrates, preferentially
      lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE). Moreover,
      using exogenous substrates, we find that the CI-976-sensitive LPAT is capable of
      using a variety of fatty acyl-CoA donors ranging in chain length from 10 to 20
      carbons. Additional characterization demonstrates that the CI-976-sensitive LPAT
      is ubiquitously expressed in rat tissues, is tightly associated with Golgi
      membranes, and has a pH optimum between pH 7.0 and 8.0. These studies further
      define a unique LPC/LPE-specific LPAT from Golgi membranes that likely has a
      novel function in membrane trafficking.

PMID- 14697245
TI  - GUG is an efficient initiation codon to translate the human mitochondrial ATP6
      gene.
AB  - A maternally inherited and practically homoplasmic mitochondrial (mtDNA)
      mutation, 8527A>G, changing the initiation codon AUG into GUG, normally coding
      for a valine, was observed in the ATP6 gene encoding the ATPase subunit a. No
      alternate Met codon could replace the normal translational initiator. The patient
      harboring this mutation exhibited clinical symptoms suggesting a mitochondrial
      disease but his mother who carried the same mtDNA mutation was healthy. The
      mutation was absent from 100 controls and occurred once amongst 44 patients
      suspected of Leber Hereditary Optic Neuropathy (LHON) but devoid of typical LHON
      mutations. In patient fibroblasts, no effect of 8527A>G mutation could be
      demonstrated on the biosynthesis of mtDNA-encoded proteins, on size and the
      content of ATPase subunit a, on ATP hydrolysis and on mitochondrial membrane
      potential. In addition, ATP synthesis was barely decreased. Therefore, GUG is a
      functional initiation codon for the human ATP6 gene.

PMID- 14697246
TI  - Methyl jasmonate treatments reduce chilling injury and activate the defense
      response of guava fruits.
AB  - Tropical fruits cannot be stored at low temperatures due to the chilling injury
      phenomena. With the goal of reducing the chilling injury, we tested 10(-4) and
      10(-5) M of methyl jasmonate (MJ) treatment before the storage of red and white
      cultivars of guava fruits at 5 degrees C for up to 15 days plus two days at 20
      degrees C. Every five days, we evaluated chilling injury index, ion leakage
      percentage, vitamin C, sugars, total phenols, and the activity of the enzymes
      lipoxygenase (LOX) and phenylalanine-ammonia lyase (PAL). We found that methyl
      jasmonate treatments reduce the chilling injury index and the ion leakage
      percentage. Furthermore, MJ did not affect vitamin C, chlorophyll, and total
      phenols. MJ increased sugar content, PAL, and LOX activities. We concluded that
      MJ reduces chilling injury and activates the fruit defense response as indicated
      by the behavior of total phenols and the increase in sugar content, PAL, and LOX
      activities.

PMID- 14697247
TI  - Regulation of haptoglobin gene expression in 3T3-L1 adipocytes by cytokines,
      catecholamines, and PPARgamma.
AB  - Factors which regulate expression of the haptoglobin (acute phase reactant) gene
      in adipocytes have been examined using 3T3-L1 cells. Haptoglobin expression was
      observed by Northern blotting in each of the major white adipose tissue depots of
      mice (epididymal, subcutaneous, mesenteric, and perirenal) and in interscapular
      brown fat. Expression occurred in mature adipocytes, but not in the stromal
      vascular fraction. In 3T3-L1 cells, haptoglobin mRNA was detected from day 4
      after the induction of differentiation into adipocytes. Lipopolysaccharide and
      the cytokines, TNFalpha and interleukin-6, resulted in substantial increases in
      haptoglobin mRNA in 3T3-L1 adipocytes; the increase (7-fold) was highest with
      TNFalpha. Increases in haptoglobin mRNA level were also induced by dexamethasone,
      noradrenaline, isoprenaline, and a beta3-adrenoceptor agonist. In contrast,
      haptoglobin mRNA was reduced by nicotinic acid and the PPARgamma agonist,
      rosiglitazone. RT-PCR showed that the haptoglobin gene was expressed in human
      adipose tissue (subcutaneous, omental). It is concluded that haptoglobin gene
      expression in adipocytes is stimulated by inflammatory cytokines,
      glucocorticoids, and the sympathetic system, while activation of the PPARgamma
      nuclear receptor is strongly inhibitory.

PMID- 14697248
TI  - Overexpression of ErbB2 receptor inhibits IGF-I-induced Shc-MAPK signaling
      pathway in breast cancer cells.
AB  - Overexpression of the ErbB2 receptor in one-third of human breast cancers
      contributes to the transformation of epithelial cells and predicts poor prognosis
      for breast cancer patients. We report that the overexpression of ErbB2 inhibits
      IGF-I-induced MAPK signaling. IGF-I-induced MAPK phosphorylation and MAPK kinase
      activity are reduced in ErbB2 overexpressing MCF-7/HER2-18 cells relative to
      control MCF-7/neo cells. In SKBR3/IGF-IR cells, reduction of ErbB2 by antisense
      methodology restores the IGF-I-induced MAPK activation. The inhibition of IGF-I
      induced MAP kinase activation in ErbB2 overexpressing breast cancer cells is
      correlated with decreased IGF-I-induced Shc tyrosine-phosphorylation, leading to
      a decreased association of Grb2 with Shc and decreased Raf phosphorylation.
      However, IGF-I-induced tyrosine-phosphorylation of IGF-I receptor and IRS-I and
      AKT phosphorylation were unaffected by ErbB2 overexpression. Consistent with
      these results, we observed that the proportion of IGF-I-stimulated proliferation
      blocked by the MAPK inhibitor PD98059 fell from 82.6% in MCF-7/neo cells to 41.2%
      in MCF-7/HER2-18 cells. These data provide evidence for interplay between the IGF
      IR and ErbB2 signaling pathways. They are consistent with the view that the IGF
      IR mediated attenuation of trastuzumab-induced growth inhibition we recently
      described is dependent on IGF-I-induced PI3K signaling rather than IGF-I-induced
      MAPK signaling.

PMID- 14697249
TI  - Retrovirus vector-mediated stable gene silencing in human cell.
AB  - RNA interference (RNAi) is the mechanism of sequence-specific, post
      transcriptional gene silencing initiated by short interfering RNAs (siRNAs)
      homologous to the gene being suppressed. siRNAs, which mediate sequence-specific
      mRNA degradation, are duplexes of about 21-23 nucleotides with 3'-overhangs
      synthesized in vitro or expressed by DNA-based vector. However, these systems
      rely on transfection for delivery and cannot generate long-term gene silencing in
      vivo. This obstacle may be circumvented by recently developed retrovirus- and
      lentivirus-delivered RNAi. Here, we describe a retroviral system for delivery of
      siRNA into cells, which can substantially down-regulate the expression of human
      p53 gene in human HepG2 cells. What's more, the G1 and S phases of cell cycle
      change dramatically in p53-down-regulated cells. These results indicate that
      retrovirus vector-delivered RNAi may be used in functional genomics and in gene
      therapy.

PMID- 14697251
TI  - Control of pulmonary surfactant secretion in adult California sea lions.
AB  - Marine mammals have a spectacular suite of respiratory adaptations to deal with
      the extreme pressures associated with deep diving. In particular, maintaining a
      functional pulmonary surfactant system at depth is critical for marine mammals to
      ensure that inspiration is possible upon re-emergence. Pulmonary surfactant is
      secreted from alveolar type II (ATII) cells and is crucial for normal lung
      function. It is not known whether ATII cells have the ability to continue to
      secrete pulmonary surfactant under pressure, or how secretion is maintained and
      controlled. We show here that surfactant secretion in California sea lions
      (Zalophus californianus) was increased after high pressures (25 and 50 atm) of
      short duration (30 min), but was unaffected by high pressures of long duration (2
      h). This is in contrast to a similar sized terrestrial mammal (sheep), where
      surfactant secretion was increased after high pressures of both long and short
      duration. Z. californianus and terrestrial mammals also show similar responses to
      stimulatory hormones and autonomic neurotransmitters. It therefore seems that an
      increase in the quantity of surfactant in seal lungs after diving is most likely
      caused by mechanostimulation induced by pressure and volume changes, and that
      seals are adapted to maintain constant levels of surfactant under long periods of
      high pressure.

PMID- 14697250
TI  - Multi-wavelength immunoassays using surface plasmon-coupled emission.
AB  - We describe a new method for multi-wavelength immunoassays using surface plasmon
      coupled emission (SPCE). This phenomenon is coupling of excited fluorophores with
      a nearby thin metal film, in our case silver, resulting in strongly directional
      emission into the underlying glass substrate. The angle at which the radiation
      propagate through the prism depends on the surface plasmon angle for the relevant
      wavelength. These angles depend on emission wavelength, allowing measurement of
      multiple analytes using multiple emission wavelengths. We demonstrated this
      possibility using antibodies labeled with either Rhodamine Red-X or AlexaFluor
      647. These antibodies were directed against an antigen protein bound to the
      silver surface. The emission from each labeled antibody occurred at a different
      angle on the glass prism, allowing independent measurement of surface binding of
      each antibody. This method of SPCE immunoassays can be readily extended to 4 or
      more wavelengths.

PMID- 14697252
TI  - A study on the fabrication of chemically modified bacteriorhodopsin film and its
      photochemical properties.
AB  - Chemically modified bacteriorhodopsin (BR) films embedded in gelatin matrix were
      fabricated. It was found that chemically modified BR/gelatin film remained the
      original conformation of BR and possessed homogeneity. Then, the photochemical
      conversion from all-trans O state to 9-cis P state in the chemically modified BR
      film/gelatin was investigated. For comparison purpose, the same conversion in the
      wild-type BR (BRwt) film was also presented here. To our know, it is the first
      report to show that the absorption changes of the P state in the chemically
      modified BR film were larger than in the BRwt film upon illumination with red
      light at the low actinic power density.

PMID- 14697253
TI  - Identification of a tissue-non-specific homologue of axonal fasciculation and
      elongation protein zeta-1.
AB  - Fasciculation and elongation protein zeta-1 (FEZ1) is a mammalian orthologue of
      the Caenorhabditis elegans UNC-76 protein involved in the axonal outgrowth and
      fasciculation and promotes neurite extension of PC12 cells through interaction
      with protein kinase C zeta (PKCzeta). The gene coding for FEZ2, a homologue of
      FEZ1, has also been reported in rat and human. In this study, we compared mRNA
      expression of FEZ1 and FEZ2 in adult rat tissues and mouse embryos by Northern
      blot and in situ hybridization analyses. In contrast to FEZ1 whose mRNA is
      expressed almost exclusively in rat brain and temporarily around the neurogenesis
      stage of mouse embryos, the message for FEZ2 is detected weakly in most tissues
      and abundantly throughout the mouse embryonic stages. Similar to FEZ1, FEZ2
      interacted with PKCzeta and induced neurite extension of PC12 cells when
      coexpressed with a constitutively active mutant of PKCzeta. These results suggest
      that FEZ2 plays an important role in the morphological changes of various cells
      by associating with PKCzeta in a tissue-non-specific manner.

PMID- 14697254
TI  - Yeast Agp2p and Agp3p function as amino acid permeases in poor nutrient
      conditions.
AB  - The gene AGP2 and the ORF YFL055w (here named AGP3) are classified as members of
      the yeast amino acid permease gene family. Analysis of the growth of multiply
      mutant strains in which these genes are disrupted shows that both encode
      permeases capable of supplying branched chain, and other, amino acids as nitrogen
      source. Both Agp2p and Agp3p are low affinity permeases for leucine (Kmapp 0.2
      0.5 mM) and are expressed at lower levels than other permeases on all media
      tested. Thus, it appears that these two permeases can function as low affinity,
      relatively non-specific, permeases with redundant functions in the cell.
      Transcription of AGP2 and AGP3 is very low but is increased in cells lacking
      other functional general amino acid permeases (Gap1p or Agp1p). These results
      suggest Agp2p and Agp3p function in amino acid transport when nitrogen sources
      are limiting and/or other permeases are inactive.

PMID- 14697255
TI  - Phe356 in the yeast Ca2+ channel component Mid1 is a key residue for viability
      after exposure to alpha-factor.
AB  - The yeast Mid1 protein is an integral membrane protein required for the viability
      of differentiated cells and Ca2+ influx induced by mating pheromone. Our previous
      study has identified a loss-of-function mutation, F356S. The F356S mutant is
      completely unable to maintain viability, but still has Ca2+ accumulation activity
      near the wild-type level. Here we further examined in detail the F356S mutation
      to unravel the function of Phe356. After exposure to the pheromone, the F356S
      mutant was not fully rescued by high extracellular Ca2+, like the mid1 null
      mutant, suggesting that Phe356 and Mid1 itself are also required for viability
      maintenance mechanism that does not involve Ca2+ signalling. Substitutions of
      hydrophilic amino acids for Phe356 caused lethality and low Ca2+ accumulation,
      but those of hydrophobic amino acids did not. Substitutions of small amino acids
      for Phe356 caused a significantly reduced viability, but did not affect Ca2+
      accumulation. We suggest that the hydrophobicity of the Phe356 residue is
      important for both viability maintenance and Ca2+ uptake, and that its size for
      viability maintenance.

PMID- 14697256
TI  - Mechanical properties of individual focal adhesions probed with a magnetic
      microneedle.
AB  - A permanent magnetic microneedle was developed to apply tensional forces to
      integrin receptors via ligand-coated magnetic microbeads while optically
      analyzing the mechanical properties of individual focal adhesions. Force
      application (130 pN for 3 s) through activated beta1 integrins produced less bead
      displacement than when unligated integrins were stressed. This strengthening
      response differed markedly on a bead-by-bead basis, correlated directly with
      local focal adhesion assembly, and was similar when analyzed at 4 degrees C,
      indicating that it was due to passive material properties of the cell.
      Viscoelastic analysis clarified that recruitment of focal adhesion proteins
      increased the local elastic stiffness of the adhesion complex without changing
      its viscous behavior. These data indicate that individual focal adhesions exhibit
      distinct mechanical properties that depend upon local focal adhesion assembly,
      and that these local variations in micromechanics can be detected and analyzed
      within living cells using the permanent magnetic microneedle technique.

PMID- 14697257
TI  - p73: in silico evidence for a putative third promoter region.
AB  - The TP73 gene, first identified in 1997, encodes the p73 protein, a p53 tumour
      suppressor homologue. The lack of mutations in the TP73 gene in cancers and the
      developmentally abnormal phenotype of the TP73 knockout mouse suggest a different
      function for TP73 gene derived proteins. An alternative promoter in the third
      intron of the TP73 gene, which produces a transcription deficient and dominant
      negative protein (DeltaNp73), produces increased complexity in the function of
      p73 proteins. Functional studies of transcriptionally active (TAp73; regulated by
      the first promoter) and DeltaNp73 (regulated by the second promoter) show that
      the TP73 gene encodes both a candidate tumour suppressor (TAp73) and an oncogene
      (DeltaNp73), with pro-apoptotic and anti-apoptotic properties, respectively. This
      "two in one" gene architecture leads us to make an in silico search for other
      probable promoter regions and transcription start sites in different introns of
      the TP73 gene. To identify such regulatory regions, we have analysed the genomic
      structure of human and mouse TP73 genes. We have found introns 1 and 4 to be
      extremely large and relatively conserved in size in mouse and human, in addition
      to intron 3, which includes the DeltaNp73 promoter. We have further characterized
      these introns by transcription factor binding motifs, transcription initiation
      sites, open reading frames, and splicing using six programs that can successfully
      identify the already characterized promoters. Our results suggest the presence of
      a candidate 2 kbp genomic DNA in the first intron of human TP73 gene, harbouring
      2 putative promoter regions, together with a similar region within intron 1 of
      the mouse gene.

PMID- 14697258
TI  - A hitherto unknown transketolase-catalyzed reaction.
AB  - Yeast transketolase, in addition to catalyzing the transferase reaction through
      utilization of two substrates--the donor substrate (ketose) and the acceptor
      substrate (aldose)--is also able to catalyze a one-substrate reaction with only
      aldose (glycolaldehyde) as substrate. The interaction of glycolaldehyde with
      holotransketolase results in formation of the transketolase reaction
      intermediate, dihydroxyethyl-thiamin diphosphate. Then the glycolaldehyde residue
      is transferred from dihydroxyethyl-thiamin diphosphate to free glycolaldehyde. As
      a result, the one-substrate transketolase reaction product, erythrulose, is
      formed. The specific activity of transketolase was found to be 0.23 U/mg and the
      apparent Km for glycolaldehyde was estimated as 140 mM.

PMID- 14697259
TI  - Intron-less processed Pcdhalpha genes in the central nervous system.
AB  - The genomic organization of the Pcdhalpha is remarkably similar to those of T
      cell receptor and immunoglobulin genes. To elucidate the somatic rearrangements
      of the genomic DNAs of Pcdhalphas in the central nervous system, we screened a
      genomic brain library of the C57BL/6 mouse strain. From this screening we
      isolated an unusual, rearranged genomic Pcdhalpha DNA. This clone contained an
      intron-less Pcdhalpha v6 gene resembling the cDNA generated from its mRNA,
      inserted into the 28S rDNA gene locus. The intron-less Pcdhalpha v6 gene
      possessed a putative promoter region and 10 nucleotide substitutions but no
      poly(A) signal. Both edges of the integration site had additional 5-bp duplicated
      sequences. PCRs that were performed using primers for intron-less Pcdhalphas
      amplified products from genomic DNAs only in the brain; moreover, using the size
      fractionated genomic DNA by sucrose density gradient centrifugation, intron-less
      Pcdhalpha is mainly amplified in the small size fraction of the genomic DNA.
      Inverted PCR for this small size fraction also amplifies the Pcdhalphas
      connecting the both ends with repeat sequences. These features suggest the
      somatic reverse-transcription, circularization, and rare occasion of integration
      into the genome of Pcdhalpha in the brain.

PMID- 14697260
TI  - NO-donating aspirin inhibits intestinal carcinogenesis in Min (APC(Min/+)) mice.
AB  - The chemopreventive effect of nitric oxide-releasing aspirin (NO-ASA) against
      gastrointestinal tumorigenesis was evaluated in Min (APC(Min/+)) mice. NO-ASA
      consists of a traditional ASA that bears covalently attached to it an NO
      releasing moiety. Four groups (N=10) of six-week-old female C57BL/6J APC(Min/+)
      and the corresponding C57BL/6J(+/+) wild type mice were treated either with
      vehicle or NO-ASA 100 mg/kg/day intrarectally for 21 days. There were no signs of
      overt toxicity including gastrointestinal toxicity from NO-ASA. Vehicle treated
      Min mice had 24.7 +/- 3.8 tumors (mean +/- SEM) and NO-ASA treated Min mice had
      10.1 +/- 1.4 tumors (59% reduction; P<0.001). Wild type mice showed no tumors. NO
      ASA did not affect cell proliferation in small intestinal mucosa, determined by
      immunohistochemical staining for PCNA. Our findings establish the strong
      inhibitory effect of NO-ASA in intestinal carcinogenesis in the Min mouse and
      suggest that this agent merits further evaluation as a chemopreventive agent
      against colon cancer.

PMID- 14697261
TI  - Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1)
      affecting transport functions.
AB  - Organic cation transporter OCT1 (SLC22A1) plays an essential role in absorption,
      distribution, and excretion of various xenobiotics including therapeutically
      important drugs. In the present study, we analyzed the functional properties of
      the single nucleotide polymorphisms (SNPs) in SLC22A1 gene found in Japanese
      control individuals. Four mutations resulting in the amino acid changes (F160L,
      P283L, R287G, and P341L) were functionally characterized in Xenopus oocyte
      expression system. Two new SNPs, identified in Japanese population, P283L and
      R287G exhibited no uptake of both [14C]TEA and [3H]MPP+, although their protein
      expressions were detected in the plasma membrane of the oocytes injected with
      their cRNAs. Uptake of [14C]TEA by P341L was reduced to 65.1% compared to wild
      type, whereas F160L showed no significant change in its transport activity. This
      study suggests that the newly found OCT1 variants will contribute to inter
      individual variations leading to the differences in cationic drug disposition and
      perhaps certain disease processes.

PMID- 14697262
TI  - An amino acid substitution attributable to insecticide-insensitivity of
      acetylcholinesterase in a Japanese encephalitis vector mosquito, Culex
      tritaeniorhynchus.
AB  - A cDNA sequence encoding a Drosophila Ace-paralogous acetylcholinesterase (AChE)
      precursor of 701 amino acid residues was identified as the second AChE gene
      (Ace2) transcript from Culex tritaeniorhynchus. The Ace2 gene is tightly linked
      to organophosphorus insecticide (OP)-insensitivity of AChE on chromosome 2. The
      cDNA sequences were compared between an insecticide-susceptible strain and the
      resistant strain, TYM, that exhibits a 870-fold decrease in fenitroxon
      sensitivity of AChE. Two amino acid substitutions were present in TYM mosquitoes.
      One is F455W whose homologous position in Torped AChE (Phe331) is located in the
      vicinity of the catalytic His in the acyl pocket of the active site gorge. The
      other substitution is located to a C-terminal Ile697 position that apparently
      seems to be excluded from the mature protein and is irrelevant to catalytic
      activity. The F455W replacement in the Ace2 gene is solely responsible for the
      insecticide-insensitivity of AChE in TYM mosquitoes.

PMID- 14697263
TI  - Temperature may influence and regulate NF-YB expression in toad oocyte.
AB  - Fully grown oocytes derived from Bufo gargarizans maintained at relatively low
      temperatures (4 degrees C, LTE-oocytes) acquire the competence to resume normal
      meiosis. In contrast, fully grown oocytes derived from toads maintained at
      relatively high temperatures (28 degrees C, HTE-oocytes) never acquire maturation
      competence. By suppression subtractive hybridization, we obtained 18 ESTs
      preliminarily thought to be preferentially expressed in LTE-oocytes; of these,
      TS1-4 shared homology with the human and mouse NF-YB genes. We cloned the full
      length toad NF-YB gene by RACE and identified three alternatively spliced
      transcripts: tNF-YB1, tNF-YB2, and tNF-YB3 (GenBank Accession Nos. AY442015,
      AY442016, and AY442017, respectively). Toad NF-YB was differentially transcribed
      and translated in LTE-oocytes versus HTE-oocytes, likely resulting in
      differential CCAAT-binding and/or transcriptional activity of NF-Y. Furthermore,
      toad cyclin B2 was differentially transcribed at high and low temperatures. Taken
      together, this report of the differential expression of toad NF-YB at different
      temperatures is the first evidence that temperature may influence and regulate NF
      YB expression.

PMID- 14697264
TI  - NAD(P)H oxidase inhibitor prevents blood pressure elevation and cardiovascular
      hypertrophy in aldosterone-infused rats.
AB  - Increased bioavailability of reactive oxygen species (ROS) has been implicated in
      the pathogenesis of mineralocorticoid hypertension. To find out the source of
      ROS, we evaluated the role of NAD(P)H oxidase in blood pressure (BP) elevation,
      cardiovascular hypertrophy, and fibrosis in aldosterone-salt rats. Aldosterone
      infusion (0.75 microg/h) significantly increased BP, which is attenuated by
      apocynin (1.5 mmol/L). Cardiac hypertrophy developed by aldosterone infusion was
      also normalized with apocynin. Greater mRNA for p22phox and NAD(P)H oxidase
      activity (more than twofold) in aorta of aldosterone-infused rats was reduced in
      apocynin-treated rats. Aldosterone infusion increased marginally procollagen I
      and III expression in LV compared to controls and apocynin decreased procollagen.
      Masson's Trichrome stain showed increased cardiac perivascular fibrosis, which
      was reduced by apocynin. These results suggest that NAD(P)H oxidase plays an
      important role in cardiovascular damage associated with mineralocorticoid
      hypertension.

PMID- 14697265
TI  - Microtubules-associated intracellular localization of the NH2-terminal cellular
      prion protein fragment.
AB  - By utilizing double-labeled fluorescent cellular prion protein (PrPC), we
      revealed that the NH2-terminal and COOH-terminal PrPC fragments exhibit distinct
      distribution patterns in mouse neuroblastoma neuro2a (N2a) cells and HpL3-4, a
      hippocampal cell line established from prnp gene-ablated mice [Nature 400 (1999)
      225]. Of note, the NH2-terminal PrPC fragment, which predominantly localized in
      the intracellular compartments, congregated in the cytosol after the treatment
      with a microtubule depolymerizer (nocodazole). Truncated PrPC with the amino acid
      residues 1-121, 1-111, and 1-91 in mouse (Mo) PrP exhibited a proper distribution
      profile, whereas those with amino acid residues 1-52 and 1-33 did not. These data
      indicate the microtubules-associated intracellular localization of the NH2
      terminal PrPC fragment containing at least the 1-91 amino acid residues.

PMID- 14697267
TI  - Cupins: the most functionally diverse protein superfamily?
AB  - The cupin superfamily of proteins, named on the basis of a conserved beta-barrel
      fold ('cupa' is the Latin term for a small barrel), was originally discovered
      using a conserved motif found within germin and germin-like proteins from higher
      plants. Previous analysis of cupins had identified some 18 different functional
      classes that range from single-domain bacterial enzymes such as isomerases and
      epimerases involved in the modification of cell wall carbohydrates, through to
      two-domain bicupins such as the desiccation-tolerant seed storage globulins, and
      multidomain transcription factors including one linked to the nodulation response
      in legumes. Recent advances in comparative genomics, and the resolution of many
      more 3-D structures have now revealed that the largest subset of the cupin
      superfamily is the 2-oxyglutarate-Fe(2+) dependent dioxygenases. The substrates
      for this subclass of enzyme are many and varied and in total amount to probably
      50-100 different biochemical reactions, including several involved in plant
      growth and development. Although the majority of enzymatic cupins contain iron as
      an active site metal, other members contain either copper, zinc, cobalt, nickel
      or manganese ions as a cofactor, with each cofactor allowing a different type of
      chemistry to occur within the conserved tertiary structure. This review discusses
      the range of structures and functions found in this most diverse of
      superfamilies.

PMID- 14697268
TI  - Purification and characterization of phytocystatins from kiwifruit cortex and
      seeds.
AB  - Kiwifruit cysteine proteinase inhibitors (KCPIs) were purified from the cortex
      and seeds of kiwifruit after inactivation of the abundant cortex cysteine
      proteinase actinidain. One major (KCPI1) and four minor cystatins were identified
      from Actinidia deliciosa ripe mature kiwifruit cortex as well as a seed KCPI from
      A. chinensis. The predominant cortex cystatin, KCPI1, inhibited clan CA, family
      C1 (papain family) cysteine proteinases (papain, chymopapain, bromelain, ficin,
      human cathepsins B, H and L, actinidain and the house dust mite endopeptidase 1),
      while cysteine proteinases belonging to other families, [clostripain (C11),
      streptopain (C10) and calpain (C2)] were not inhibited. Inhibition constants
      (K(I)) ranged between 0.001 nM for cathepsin L and 0.98 nM for endopeptidase 1.
      The K(I) (14 nM) for KCPI1 inhibiting actinidain is at least 2 orders of
      magnitude higher than for other plant proteinases measured. The cortex KCPI1 and
      a seed KCPI purified from seeds had the same N-terminal sequence
      (VAAGGWRPIESLNSAEVQDV). BLAST-matching the peptide sequence against an in-house
      generated Actinidia EST database, identified 81 cDNAs that exactly matched the
      measured KCPI1 peptide sequence. Peptide sequences of two other cortex KCPIs each
      exactly matched a predicted peptide sequence of a cDNA from kiwifruit. The
      predicted peptide sequence of KCPI1 of 116 amino acids encodes a signal peptide
      and does not contain cysteine. Without the signal peptide (mature protein), KCPI1
      has a molecular mass of approximately 11 kDa, possesses the consensus sequence
      characteristic for the phytocystatins and shows the highest homology to a
      cystatin from Citrusxparadisi (52% identity). This is the first report of
      phytocystatins from the Ericales.

PMID- 14697269
TI  - Bio-fermentation of modified flavonoids: an example of in vivo diversification of
      secondary metabolites.
AB  - A bio-fermentation technique was used for the in vivo diversification of
      flavonoid structures based on expression in Escherichia coli of six O
      methyltransferases (OMTs) from Mentha x piperita and one O-glucosyltransferase
      (GT) each from Arabidopsis thaliana and Allium cepa. Enzymes were shown to be
      regio-specific in in vitro experiments and modified a broad range of flavonoid
      substrates at various positions. Using the flavonol quercetin as a model
      substrate, we show that the product spectrum produced with the in vivo approach
      is identical to that found in vitro. Additionally, using mixed cultures of E.
      coli expressing different classes of modifying genes (OMTs and GTs), the
      production of polymethylated flavonoid glucosides was observed. This report
      demonstrates the potential to increase the structural diversity of plant
      secondary metabolites using a multi-enzyme, bio-fermentation approach.

PMID- 14697270
TI  - The S8 serine, C1A cysteine and A1 aspartic protease families in Arabidopsis.
AB  - The Arabidopsis thaliana genome has over 550 protease sequences representing all
      five catalytic types: serine, cysteine, aspartic acid, metallo and threonine
      (MEROPS peptidase database, http://merops.sanger.ac.uk/), which probably reflect
      a wide variety of as yet unidentified functions performed by plant proteases.
      Recent indications that the 26S proteasome, a T1 family-threonine protease, is a
      regulator of light and hormone responsive signal transduction highlight the
      potential of proteases to participate in many aspects of plant growth and
      development. Recent discoveries that proteases are required for stomatal
      distribution, embryo development and disease resistance point to wider roles for
      four additional multigene families that include some of the most frequently
      studied (yet poorly understood) plant proteases: the subtilisin-like, serine
      proteases (family S8), the papain-like, cysteine proteases (family C1A), the
      pepsin-like, aspartic proteases (family A1) and the plant matrixin,
      metalloproteases (family M10A). In this report, 54 subtilisin-like, 30 papain
      like and 59 pepsin-like proteases from Arabidopsis, are compared with S8, C1A and
      A1 proteases known from other plant species at the functional, phylogenetic and
      gene structure levels. Examples of structural conservation between S8, C1A and A1
      genes from rice, barley, tomato and soybean and those from Arabidopsis are noted,
      indicating that some common, essential plant protease roles were established
      before the divergence of monocots and eudicots. Numerous examples of tandem
      duplications of protease genes and evidence for a variety of restricted
      expression patterns suggest that a high degree of specialization exists among
      proteases within each family. We propose that comprehensive analysis of the
      functions of these genes in Arabidopsis will firmly establish serine, cysteine
      and aspartic proteases as regulators and effectors of a wide range of plant
      processes.

PMID- 14697271
TI  - Relationships in subtribe Diocleinae (Leguminosae; Papilionoideae) inferred from
      internal transcribed spacer sequences from nuclear ribosomal DNA.
AB  - The complete sequences of nuclear ribosomal DNA (nrDNA) internal transcribed
      spacer regions (ITS/5.8S) were determined for species belonging to six genera
      from the subtribe Diocleinae as well as for the anomalous genera Calopogonium and
      Pachyrhizus. Phylogenetic trees constructed by distance matrix, maximum parsimony
      and maximum likelihood methods showed that Calopogonium and Pachyrhizus were
      outside the clade Diocleinae (Canavalia, Camptosema, Cratylia, Dioclea,
      Cymbosema, and Galactia). This finding supports previous morphological,
      phytochemical, and molecular evidence that Calopogonium and Pachyrhizus do not
      belong to the subtribe Diocleinae. Within the true Diocleinae clade, the
      clustering of genera and species were congruent with morphology-based
      classifications, suggesting that ITS/5.8S sequences can provide enough
      informative sites to allow resolution below the genus level. This is the first
      evidence of the phylogeny of subtribe Diocleinae based on nuclear DNA sequences.

PMID- 14697272
TI  - A rac-like small G-protein from Brassica campestris activates a PKC-dependent
      phospholipase D.
AB  - A cDNA clone encoding a rac-like small GTP binding protein was isolated from a
      cDNA library of Chinese cabbage (Brassica campestris L. ssp. pekinensis) flower
      buds and named Brac1. The Brac1 cDNA contains an open reading frame encoding 198
      amino acid residues with an estimated molecular mass of 21,690 Da and this coding
      region has conserved residues and motifs unique to the Rho subfamily of proteins.
      The deduced amino acid sequence of the Brac1 protein is closely related to that
      of Arabidopsis thaliana Arac3 (91%), but it shares relatively little homology
      with other members of the Ras superfamily (about 30% identity). To further
      characterize Brac1, a pGBrac1 expression vector consisting of PCR-amplified Brac1
      cDNA plus glutathione S-transferase (GST) and pBKS(+)II was used to purify the
      protein. Using a PEI-cellulose/TLC plate, GTPase activity of this protein was
      confirmed and competition binding studies, using the guanine nucleotides, ATP,
      UTP and CTP, revealed that the di- and triphosphate forms of guanine nucleotides
      strongly bind Brac1. Membrane-bound PLD activity was synergistically enhanced by
      Brac1 in the presence of protein kinase C, but not in the presence of ARF (ADP
      ribosylation factor). Genomic analysis indicated that Brac1 belongs to a
      multigene family. Brac1 transcripts were expressed in all the organs of Brassica,
      but were especially prevalent in flower buds.

PMID- 14697273
TI  - Effects of soybean Kunitz trypsin inhibitor on the cotton boll weevil (Anthonomus
      grandis).
AB  - The cotton boll weevil, Anthonomus grandis, is an economically important pest of
      cotton in tropical and subtropical areas of several countries in the Americas,
      causing severe losses due to their damage in cotton floral buds. Enzymatic assays
      using gut extracts from larval and adult boll weevil have demonstrated the
      presence of digestive serine proteinase-like activities. Furthermore, in vitro
      assays showed that soybean Kunitz trypsin inhibitor (SKTI) was able to inhibit
      these enzymes. Previously, in vivo effects of black-eyed pea trypsin chymotrypsin
      inhibitor (BTCI) have been demonstrated towards the boll weevil pest. Here, when
      neonate larvae were reared on an artificial diet containing SKTI at three
      different concentrations, a reduction of larval weight of up to 64% was observed
      for highest SKTI concentration 500 microM. The presence of SKTI caused an
      increase in mortality and severe deformities of larvae, pupae and adult insects.
      This work therefore represents the first observation of a Kunitz trypsin
      inhibitor active in vivo and in vitro against A. grandis. Bioassays suggested
      that SKTI could be used as a tool in engineering crop plants, which might exhibit
      increased resistance against cotton boll weevil.

PMID- 14697274
TI  - Isolation of alpha-glusosidase inhibitors from hyssop (Hyssopus officinalis).
AB  - alpha-Glucosidase inhibitory activity was found in aqueous methanol extracts of
      dried hyssop (Hyssopus officinalis) leaves. Active principles against alpha
      glucosidase, prepared from rat small intestine acetone powders, were isolated and
      characterized. The structures of these isolated compounds were determined to be
      (7S, 8S)-syringoylglycerol-9-O-(6'-O-cinnamoyl)-beta-D-glucopyranoside and (7S,
      8S)-syringoylglycerol 9-O-beta-D-glucopyranoside by analysis of physical and
      spectroscopic data (FDMS, 1H NMR, 13C NMR, HMQC, and HMBC experiments) together
      with chemical syntheses.

PMID- 14697275
TI  - Dihydrophenanthrenes and other antifungal stilbenoids from Stemona cf. pierrei.
AB  - Three new dihydrophenanthrenes, stemanthrenes A-C, along with the new
      dihydrostilbene stilbostemin G were isolated and identified from the underground
      parts of Stemona cf. pierrei together with the known pinosylvin, 4'
      methylpinosylvin, dihydropinosylvin, stilbostemins B, D, and E as well as the
      pyrrolo[1,2-a]azepine alkaloids protostemonine and stemonine. The structures of
      all new stilbenoids, elucidated by NMR analyses, showed a common substitution
      pattern for aromatic ring A and characteristic C-methylations for ring B. The
      trivial name racemosol, previously reported for S. collinsae, was renamed to
      stemanthrene D due to its priority for another compound. Bioautographic tests on
      TLC plates with Cladosporium herbarum displayed high antifungal activity for
      compounds with an unsubstituted aromatic ring A, e.g. pinosylvin, but only weak
      effects for the higher substituted stilbostemin G and stemanthrenes A-C. Similar
      results were obtained by germ tube inhibition of five microfungi using 2-fold
      serial broth dilutions determined by a microplate reader. Because of weak
      inhibition and chemical instability of stemanthrenes, no EC(50) and EC(90) values
      could be calculated.

PMID- 14697276
TI  - Biotransformation of ent-13-epi-manoyl oxides difunctionalized at C-3 and C-12 by
      filamentous fungi.
AB  - Biotransformation of ent-3beta,12alpha-dihydroxy-13-epi-manoyl oxide with
      Fusarium moniliforme gave the regioselective oxidation of the hydroxyl group at C
      3 and the ent-7beta-hydroxylation. The action of Gliocladium roseum in the 3,12
      diketoderivative originated monohydroxylations at C-1 and C-7, both by the ent
      beta face, while Rhizopus nigricans produced hydroxylation at C-7 or C-18,
      epoxidation of the double bond, reduction of the keto group at C-3, and combined
      actions as biohydroxylation at C-2/epoxidation of the double bond and
      hydroxylation at C-7/reduction of the keto group at C-3. In the ent-3-hydroxy-12
      keto epimers, G. roseum originated monohydroxylations at C-1 and C-7 and R.
      nigricans originated the oxidation at C-3 as a major transformation, epoxidation
      of double bond and hydroxylation at C-2. Finally, in the ent-3beta-hydroxy epimer
      R. nigricans also originated minor hydroxylations at C-1, C-6, C-7 and C-20 and
      F. moniliforme produced an hydroxylation at C-7 and a dihydroxylation at C-7/C
      11.

PMID- 14697277
TI  - Long-chain alkenones and related compounds in the benthic haptophyte Chrysotila
      lamellosa Anand HAP 17.
AB  - The neutral lipid compositions of the coastal haptophyte Chrysotila lamellosa HAP
      17 grown in batch culture at 10 and 20 degrees C have been determined. A
      comparison was also made between the lipid compositions of cells harvested in
      early and late stationary phase. This species contains a suite of very long-chain
      C(37)-C(40) alkenones and alkenoates as found in a few microalgae from the
      Haptophyta. The distributions of these compounds show some differences to earlier
      reports of different strains of this alga, which are only in part attributable to
      culture conditions. A suite of long-chain alkenols, the reduced form of the
      alkenones, was characterized for the first time. The abundance of these compounds
      was only 1.5% of that of the corresponding alkenones, and the relative proportion
      of C(37)-C(38) constituents depended on growth temperature. These data show that
      haptophyte algae are a possible source of the alkenols found in some marine
      sediments, but the small amounts found suggest that other sources such as
      bacterial reduction of alkenones are more likely in highly reducing sediments. A
      mixture of C(29)-C(33) n-alkenes, dominated by the C(31:1) monoene, was found in
      marked contrast to previous analyses of other strains which reported only the
      presence of a C(31:2) diene. The sterol distribution included the common
      haptophyte sterol 24alpha-methylcholesta-5,22E-dien-3beta-ol (epi-brassicasterol)
      as well as significant amounts of Delta(5)- and Delta(5,22)-C(29) sterols.

PMID- 14697278
TI  - ent-Clerodane diterpenes and other constituents from the liverwort Adelanthus
      lindenbergianus (Lehm.) Mitt.
AB  - Eleven ent-clerodanes, 13-hydroxy-cis-ent-cleroda-3,14-diene, 15-hydroxy-cis-ent
      cleroda-3,13(E)-diene, 1beta,12:15,16-diepoxy-cis-ent-cleroda-13(16),14-dien
      18alpha,6alpha-olide, 8beta,12:15, 16-diepoxy-cis-ent-cleroda-13(16),14-dien
      18alpha,6alpha-olide, 1beta,16:15,16-diepoxy-cis-ent-cleroda-12,14-dien
      18alpha,6alpha-olide, 7beta,12:8beta,12-diepoxy-15-hydroxy-cis-ent-cleroda-13-en
      16,15:18alpha,6alpha-diolide, 7beta,12:8beta,12-diepoxy-16-hydroxy-cis-ent
      cleroda-13-en-15,16:18alpha,6alpha-diolide, 1alpha-acetoxy-8beta,12-epoxy-15
      hydroxy-cis-ent-cleroda-13-en-16,15:18alpha,6alpha-diolide, 1beta,12-epoxy-16
      hydroxy-cis-ent-cleroda-13-en-15,16:18alpha,6alpha-diolide, 8beta,12-epoxy-15
      hydroxy-trans-cleroda-13-en-16,15:18alpha,6alpha-diolide, 8beta,12-epoxy-16
      hydroxy-trans-cleroda-13-en-15,16:18alpha,6alpha-diolide along with the known
      clerodane diterpenes anastreptin and orcadensin have been isolated from the
      liverwort Adelanthus lindenbergianus (Lehm.) Mitt. Furthermore, three eudesmane
      sesquiterpenes together with the known (-)-1beta,10-epoxyaristolan, 3,4-seco
      4(23),20(29)-lupadien-3,28-dicarboxylic acid dimethyl ester and two acetophenone
      derivatives were identified by spectroscopic methods, essentially MS and NMR
      experiments.

PMID- 14697280
TI  - Academic medicine's core values: what do they mean?

PMID- 14697281
TI  - Increased platelet aggregation and production of platelet-derived microparticles
      after surgery for upper gastrointestinal malignancy.
AB  - BACKGROUND: Since platelet function is known to play a major role in arterial
      thrombosis, we investigated postsurgery alterations in platelet function that
      might predispose patients with upper gastrointestinal malignancy to postoperative
      thrombotic complications. SUBJECTS AND METHODS: Shear-induced platelet
      aggregation (SIPA) in platelet-rich plasma was measured in 23 patients who
      elected to undergo abdominal surgery. Measurement was done by cone-plate
      viscometer under low shear stress (12 dyn/cm(2)), a physiological condition, and
      under high shear stress (108 dyn/cm(2)), a pathological condition that simulates
      in vivo conditions such as those in stenotic arteries. Platelet microparticle
      (PMP) formation was analyzed by flow cytometry. Plasma von Willebrand factor
      (vWF) was also measured. RESULTS: SIPA under high shear stress was significantly
      enhanced from 44.0 +/- 13.4% preoperatively to 69.5 +/- 15.8% on postoperative
      day (POD) 1, and it returned to preoperative levels on POD 14. PMP formation
      under high shear stress was enhanced before surgery (140.8 +/- 38.7%) compared to
      that under a static condition, and the enhancement was further augmented on POD 1
      (219.1 +/- 49.3%). The enhancement of SIPA and PMP formation had no association
      with disease stage. vWF levels increased significantly on POD 1. Exogenous vWF
      augmented SIPA and PMP formation under high shear stress, and this augmentation
      was inhibited by anti-vWF antibody. CONCLUSIONS: Because PMPs are highly
      procoagulant, increased SIPA and PMP formation induced by surgical intervention
      possibly contribute to thrombotic complications. Blockage of platelet interaction
      with vWF may prevent arterial thrombus formation perioperatively.

PMID- 14697282
TI  - Involvement of superoxide anion in the pathogenesis of simple mechanical
      intestinal obstruction.
AB  - BACKGROUND: Mechanism underlying the pathogenesis of mechanical intestinal
      obstruction has been suggested to be closely associated with bowel inflammatory
      response in which reactive oxygen metabolites might play an important role. This
      study was designed to examine the involvement of superoxide anion in the
      obstruction-induced intestinal injury. MATERIALS AND METHODS: Rats were randomly
      aasigned to four groups: sham, obstruction, obstruction with polyethylene glycol
      (PEG), and obstruction with polyethylene glycol-superoxide dismutase (PEG-SOD)
      groups. A ligation at the ileum 20 cm proximal to the cecum was created under
      anesthesia. The superoxide anion production and the pathological manifestations
      in the obstructed intestine were measured after 24 h of ligation. RESULTS: There
      were significant intestinal shortening, distension, fluid accumulation and
      mucosal damage in the segment proximal to the ligation site. Pronounced
      generation of superoxide anion was found in the obstructed intestinal segment.
      Supplement of SOD, a superoxide free radicals scavenger, ameliorated obstruction
      induced bowel distension, fluid accumulation and mucosal damage. CONCLUSION:
      These data suggest superoxide anion is one of the important mediators in the
      pathophysiologic changes of simple mechanical intestinal obstruction.

PMID- 14697283
TI  - Satellite cell proliferation, reinnervation, and revascularization in human free
      microvascular muscle flaps.
AB  - BACKGROUND: Satellite cell proliferation, reinnervation, and revascularization
      were studied in human nonreinnervated free microvascular muscle flaps to
      characterize mechanisms of muscle regeneration after flap surgery. MATERIALS AND
      METHODS: Patient biopsies (n = 19) were taken at operation and five timepoints up
      to 9 months after operation, and corresponding clinical data were obtained.
      Immunohistochemistry for Ki-67 was used to detect proliferating satellite cells,
      CD-31 to identify endothelial cells, and S-100 and PGP 9.5 proteins to detect
      reinnervation. RESULTS: Two weeks after operation, the expression of PGP 9.5 and
      S-100 had virtually disappeared in all larger nerve fibers and half of smaller
      nerve fibers. By 6 months, however, a strong expression of PGP 9.5 and S-100 had
      reappeared in larger nerve fibers in three of four flaps, suggesting that
      reinnervation had taken place. The number of mitotic satellite cells already
      peaked at 2 weeks, indicating onset of muscle regeneration. The number of
      intramuscular capillaries first increased but later decreased to lower than
      original level. Flaps with more muscle volume showed more reinnervation and
      satellite cell mitotic activity. In cases of a delay occurring in reconstructive
      surgery, a low level of reinnervation was seen. CONCLUSION: Three patients of
      four showed spontaneous muscle reinnervation in microvascular free flaps with
      satellite cell activation followed by restored morphology. Late reconstruction
      and obesity lead to poor reinnervation, placing emphasis on timing of surgery and
      patient selection.

PMID- 14697284
TI  - Inhibitory effect of brachytherapy on intimal hyperplasia in arteriovenous
      fistula.
AB  - PURPOSE: To determine whether endovascular radiation can inhibit intimal
      hyperplasia in a swine model of hemodialysis access. MATERIALS AND METHODS:
      Polytetrafluoroethylene arteriovenous grafts (6 mm in diameter) were placed
      between the common carotid artery and the external jugular vein bilaterally in 8
      pigs. Two days after the surgery, fistulography was performed. Gamma radiation
      (12 Gy) was delivered endovascularly to one of the grafts at the venous
      anastomosis by using an iridium(192) source. Thus, the other graft in each pig
      served as an untreated control. Fistulas were evaluated with fistulography or
      venography 6 week after radiation. All grafts were then harvested for
      histological and immunohistochemical examination. RESULTS: Seven grafts on the
      treated side and 5 grafts on the control side remained patent for at least 6
      weeks. Angiography demonstrated that the percentage stenosis at the venous
      anastomosis was significantly lower for the treated group (15.9 +/- 14.1 versus
      32.6 +/- 16.7%, P = 0.045). Histopathologic analyses revealed that the mean
      intimal area and maximal intimal thickness were significantly lower with reduced
      smooth muscle cell proliferation at the venous anastomosis on the treated side
      compared to the control side (0.68 +/- 0.30 versus 1.06 +/- 0.29 mm(2), P =
      0.017, and 0.18 +/- 0.08 versus 0.26 +/- 0.07 mm, P = 0.004, respectively). The
      residual lumen was significantly greater for the treated group (1.59 +/- 0.42
      versus 1.06 +/- 0.37 mm(2), P = 0.031). No significant differences were found in
      the area, nor maximal thickness in the vein either proximal or distal to the
      anastomosis between the two groups. CONCLUSIONS: In an animal model of
      hemodialysis access, brachytherapy with iridium(192) delivered 2 days after graft
      implantation reduces intimal hyperplasia and stenosis at the venous anastomosis.
      The reduced smooth-muscle cells found in the radiated veins suggests that
      brachytherapy may exert its effect on neointimal formation by inhibition of
      smooth muscle cell proliferation.

PMID- 14697285
TI  - Hemodynamic effects of the vacuum-assisted closure device on open mediastinal
      wounds.
AB  - BACKGROUND: Application of the Vacuum-Assisted Closure device (VAC) to open
      sternal wounds has negative hemodynamic effects. We hypothesized that the
      interposition of a muscle flap attenuates these negative hemodynamic effects.
      MATERIALS AND METHODS: After institutional approval, monitoring lines were placed
      in anesthetized, ventilated pigs. Through a median sternotomy, sonometric
      crystals were strategically positioned around the left ventricle. A rectus flap
      was rotated over the mediastinal wound, and the VAC was placed over the flap.
      After baseline measurements, a vacuum of 125 mmHg [Group (GP) 1, n = 5] or 50
      mmHg (GP2, n = 6) was initiated. Hemodynamics were recorded every 15 min for 1.5
      h, and 15 min after cessation of the vacuum therapy. GP3 (n = 6) underwent
      intermittent VAC cycling (on 5 min/off 2 min). Significance determined by t test.
      RESULTS: While non-flapped animals had significant detriment in both left
      ventricular filling volume and cardiac output, flapped animals had insignificant
      depression of both parameters. CONCLUSION: Application of muscle flaps to sternal
      wounds prior to VAC therapy significantly attenuates the negative hemodynamic
      effects seen when the VAC is used alone.

PMID- 14697286
TI  - Effective use of human simulators in surgical education.
AB  - BACKGROUND: We initiated a teaching module utilizing a human simulator midway
      through 2001-2002 to improve student skills specific to the evaluation of
      patients in shock during a required clerkship in surgery for fourth-year medical
      students. We tested the hypothesis that student skills would improve after
      implementation of this module and identified factors that predicted student
      performance. MATERIALS AND METHODS: Students (n = 86) chose one of two hospital
      sites for a clerkship that focuses on the care of acutely ill surgical patients.
      A case-based lecture focusing on the diagnosis and management of a patient in
      shock was replaced midway through the academic year by a simulator session with a
      computerized life-sized mannequin. A standardized clinical final evaluation
      (OSCE) was used to assess student skills. We evaluated the effect of the
      simulator session and other factors on student exam performance using univariate
      and multivariate analysis. RESULTS: The site of the clerkship and the simulator
      session were significant factors affecting the OSCE score identified by ANOVA, P
      < 0.05. A stepwise multiple regression analysis testing the effect of simulator
      module, site, time of year, prior NBME subject exam, and prior OSCE during the
      third year clerkship identified that the simulator module was the only
      independent factor that modeled performance on all shock stations, P < 0.01.
      CONCLUSIONS: In a clerkship that already emphasized faculty facilitated case
      based learning, the use of a teaching module employing a human simulator
      significantly improved test scores. This study supports the efficacy of human
      simulators to improve student skills related to the management of complex
      critically ill patients.

PMID- 14697287
TI  - The efficacy of tyrosine kinase inhibitors on human pancreatic cancer cell lines.
AB  - We attempted to determine potential therapeutic targets in pancreatic cancer by
      performing microarray analysis and targeted chemotherapy on three human
      pancreatic cancer cell lines. We used a microarray to screen 847 genes involved
      in cytokine signaling, signal transduction, and transcription. Tyrosine kinases
      represented a common target driving proliferation among the three cell types. We
      tested the ability of Gleevec (STI-571), Lavendustin, Herbimycin, and Genistein
      to inhibit the proliferation of cells in culture as assessed by the MTT
      assay.Eighteen genes were found to be commonly expressed by the three cell lines.
      Of these, six (33%) included tyrosine phosphorylation signaling as part of the
      pathway. The most highly expressed common transcript was the EphB3 receptor,
      which is a tyrosine kinase. Herbimycin and Genistein were able to inhibit the
      proliferation of all three cell lines in a dose dependent manner, with a mean
      IC(50) of 1.71 microM and 223 microM, respectively; whereas Lavendustin and
      Gleevec were ineffective in the inhibition of proliferation. Transcriptional
      profiling yielded common targets and insights into the biology of cells in
      culture. Herbimycin- and Genistein-based kinase inhibitors may offer potential
      and should be tested in other in vivo models for their ability to inhibit the
      growth of pancreatic cancer.

PMID- 14697288
TI  - Up-regulation of hepatocyte growth factor caused by an over-expression of
      transforming growth factor beta, in the rat model of fulminant hepatic failure.
AB  - BACKGROUND: The role of transforming growth factor beta (TGF-beta), a potent
      regulator of cellular growth, was investigated in the rat model of fulminant
      hepatic failure (FHF). MATERIALS AND METHODS: The rat FHF model was created by a
      combination of a 68% partial hepatectomy (PH) and 7% of necrosis (each n = 25 in
      Groups 1, 2 and 3). Adenovirus mediated gene transfer of mature human TGF-beta1
      gene was performed by the systemic injection of AxCAhTGFb1 (1 x 10(9) pfu) in
      Group 1, 3 days before FHF. In control Groups 2 and 3, recombinant lacZ
      adenovirus (AxCAlacZ, Group 2) and normal saline (1 ml, Group 3) were used,
      instead of AxCAhTGFb1. RESULTS: An excessive expression of TGF-beta1 in Group 1
      resulted in an inhibition of hepatocyte proliferation (24-48 h after FHF) and
      gaining of liver weight (24-48 h), increased expression of HGF in liver tissue
      (24 h), and decreased expression of TGF-alpha (24 h), compared to those in
      control Groups 2 and 3. Serum IL-6 levels were also elevated by a TGF-beta1 over
      expression at 24 hrs after FHF in Group 1. CONCLUSIONS: The forced expression of
      TGF-beta1 in the FHF liver yields both a secondary increase of HGF production and
      a suppression of liver regeneration, which might explain the mechanism of
      increased serum HGF observed in a clinical FHF. TGF-beta1 is thus thought to have
      an important role in inhibiting liver regeneration after FHF.

PMID- 14697289
TI  - Macrophage overgrowth affects neighboring nonovergrown encapsulated islets.
AB  - BACKGROUND: Encapsulation significantly prolongs islet graft survival in the
      absence of immunosuppression. However, encapsulated islet graft survival is
      limited to periods of several months. Part of the encapsulated islet graft is
      affected by a nonprogressive pericapsular overgrowth. To investigate whether
      macrophages on overgrown capsules affect neighboring nonovergrown encapsulated
      islets, encapsulated islets were studied during coculture. MATERIALS AND METHODS:
      Encapsulated islet function, islet vitality, and islet cell replication were
      assessed, as well as the mRNA expression of Bcl-2, Bax, inducible nitric oxide
      synthase, and monocyte chemoattractant protein-1 in encapsulated islets after 48
      h of culture together with microcapsules with macrophage overgrowth. Overgrown
      capsules were retrieved from the rat peritoneum, three weeks after implantation
      of an encapsulated islet graft. RESULTS: Coculture was associated with inhibition
      of the stimulated insulin secretion, with decreased cell replication, and with
      increased cell necrosis, but not with apoptosis of encapsulated islet cells. mRNA
      expression levels in encapsulated islets after coculture were not different from
      controls, except for a decrease in Bax mRNA. We found a high level of nitrite, as
      an indicator of nitric oxide production, but not an increase in inducible nitric
      oxide synthase mRNA in islets. This, in combination with the absence of increase
      in monocyte chemoattractant protein-1 mRNA and the lack of apoptosis, indicates
      that neither interleukin-1beta nor tumor necrosis factor-alpha was responsible
      for the deleterious effects of coculture on encapsulated islets. CONCLUSIONS:
      Nonovergrown encapsulated islets are affected by the overgrowth on encapsulated
      islets in their close proximity. This overgrowth contains macrophages that
      produce nitric oxide which, rather than cytokines, may be held responsible for
      the deleterious effect on the neighboring encapsulated islets.

PMID- 14697290
TI  - Gut glutathione metabolism and changes with 7,12-DMBA and glutamine.
AB  - INTRODUCTION: The mechanism by which oral glutamine (GLN) prevents 7,12
      dimethylbenz(a)anthracene (DMBA)-induced breast cancer is unknown. While GLN
      triples the negative extraction of gut glutathione (GSH) in rats, DMBA
      significantly disrupts it. Actual gut GSH flux has not been reported. We
      hypothesized that the gut is a producer of GSH; DMBA blocks gut GSH production
      and supplemental oral GLN antagonizes this effect. MATERIALS AND METHODS: Eighty
      Sprague-Dawley rats were randomized to four groups (n = 20/group): DMBA + GLN,
      DMBA + FA, OIL + GLN, OIL + FA. Rats (age 50 days) were gavaged with a one-time
      dose of 100 mg/kg DMBA or oil. Rats were gavaged with AES-14 as GLN (1 gm/kg/day)
      or an isonitrogenous amount of Freamine (FA) from 1 week before till sacrifice at
      1 week after DMBA (greatest effect on gut GSH extraction). Arterial and portal
      blood was taken for GLN and GSH levels, and blood flow was measured using (14)C
      PAH. Gut GLN and GSH fluxes (uptake or production) were calculated. RESULTS: DMBA
      abrogated the normal GSH production (negative flux) in OIL + FA while not
      affecting GLN metabolism. GLN maintained GSH production in DMBA + GLN.
      CONCLUSIONS: Oral GLN restores to normal GSH production in DMBA-treated animals
      suggesting one of the mechanism(s) by which GLN prevents breast cancer in this
      model. Unchanged uptake of GLN in the DMBA-treated animals may indicate a block
      in GSH transport rather than actual intracellular production.

PMID- 14697291
TI  - Human C1 esterase inhibitor attenuates murine mesenteric ischemia/reperfusion
      induced local organ injury.
AB  - BACKGROUND: Complement activation contributes to ischemia and reperfusion (IR)
      initiated organ injury. C1 inhibitor (C1 Inh) inhibits the earliest steps of the
      classical and the mannose binding lectin pathways. MATERIALS AND METHODS: To
      determine whether C1 Inh prevented tissue injury, we performed intestinal IR
      experiments in BALB/c and C57BL/6 mice. RESULTS: We found that C1 Inh limits
      mucosal injury in the two strains in a dose dependent manner. Tissue damage was
      associated with the accumulation of functional polymorphonuclear cells, which was
      reduced following C1 Inh treatment. Constitutive nitric oxide synthase activity
      correlated with the development of injury in the C57BL/6 but not in the BALB/c
      mouse. CONCLUSIONS: These findings emphasize the importance of complement
      activation in ischemia/reperfusion and highlight the potential therapeutic use of
      C1 Inh in limiting or preventing damage caused by IR.

PMID- 14697292
TI  - Laser revascularization of ischemic skeletal muscle.
AB  - BACKGROUND: Clinical trials have shown that transmyocardial laser
      revascularization is an effective secondary treatment for ischemic heart disease
      patients. Laser revascularization may also provide an alternative method for
      treating peripheral vascular disease. METHODS: The purpose of this study was to
      investigate the potential for laser revascularization in ischemic skeletal
      muscle. Eighteen rabbits (3-4 kg) were instrumented chronically with transit time
      ultrasound flowprobes on both common iliac arteries. All rabbits performed graded
      exercise tests on a treadmill where maximal blood flow was recorded. Unilateral
      hindlimb ischemia was produced by ligation of one femoral artery. At week 3
      postligation, 10 rabbits received laser therapy and 8 underwent a sham surgery.
      In each of four muscles (gracilius, medialis, sartorius, and biceps femoris) 5 to
      22 laser channels were created (average = 52 channels per leg). RESULTS: At week
      3 postligation the maximal blood flow of the ischemic limb for the treated group
      was 64 +/- 3 ml/min (mean +/- SEM) and at 6 weeks postlaser therapy maximal blood
      flow increased to 75 +/- 5 ml/min. The sham surgery group had a maximal blood
      flow of 58 +/- 4 ml/min at week 3 postligation and 66 +/- 3 ml/min at week 6
      postsham surgery. CONCLUSION: These results indicate that laser therapy does not
      induce angiogenesis and vascular remodeling in the ischemic hindlimb of a rabbit
      which exceeds that seen with a sham surgery.

PMID- 14697293
TI  - Hepatic vascular inflow occlusion enhances tissue destruction during cryoablation
      of porcine liver.
AB  - BACKGROUND: Local recurrences after cryoablation of liver tumors have been
      reported at rates from 5% to 44% and can be caused by inadequate coverage of the
      tumor by the frozen region. Hepatic vascular inflow occlusion may facilitate
      ablation by enlarging the size of the frozen region and the tissue necrosis
      induced by freezing. Few studies have documented these effects of inflow
      occlusion during liver cryoablation. MATERIALS AND METHODS: Two cryolesions were
      induced in the liver of 12 pigs in a standardized set-up. Vascular inflow
      occlusion was used in six pigs during freezing. Two freeze cycles were performed
      at each location. Ice-ball volume was estimated by intraoperative magnetic
      resonance imaging. Cryolesion volume was estimated from histopathologic
      examination of the lesions 4 days after ablation. RESULTS: The median volume of
      ice-balls produced during inflow occlusion was 107% larger than for ice-balls
      produced without occlusion (P < 0.001). The median volume of cryolesions made
      during inflow occlusion was 195% larger than for cryolesions induced without
      occlusion (P < 0.001). The geometry of the ice-balls was more regular if produced
      during inflow occlusion than if not. The ice-balls produced during the second
      freeze cycle were 17% and 20% larger than the ice-ball produced during the first
      freeze for lesions made with (P = 0.01) and without (P = 0.03) inflow occlusion.
      CONCLUSIONS: Hepatic vascular inflow occlusion enables freezing of larger volumes
      of liver tissue andincreases the volume of tissue necrosis induced during
      cryoablation of porcine liver.

PMID- 14697294
TI  - Impaired gastric motility in the gastroesophageal reflux rat model: an in vitro
      study.
AB  - PURPOSE: The present study investigated the effects of acid and mixed reflux on
      the responsiveness of gastric smooth muscle in the gastroesophageal reflux (GER)
      rat model. MATERIAL AND METHODS: Three groups of rat were studied encompassing
      acid reflux, mixed reflux and sham operation. Acid reflux was induced by pyloric
      ligation (AR group) and mixed reflux was induced by jejunal ligation 1 cm distal
      to Treitz ligament (MR group). Similar surgical manipulations were carried out in
      the sham operated rats (SO group). Carbachol-, serotonin-, KCl-induced
      contractile response and nicotine-, sodium nitroprusside-, papaverine-induced
      relaxant response in isolated gastric fundus smooth muscle strips were determined
      using in vitro muscle technique 24 h after surgery. RESULTS: Isolated gastric
      fundus smooth muscle contractility to serotonin, carbachol or KCl was
      significantly reduced in the AR and MR groups with decreased Emax and pD(2)
      values compared with the SO group. Relaxant responses to nicotine was
      significantly increased in the AR and MR groups with increased Emax and pD(2)
      values compared with the SO group. Sodium nitroprusside and papaverine-induced
      relaxant responses were similar in all of the groups and there was no change in
      agonist potency. CONCLUSION: The present study indicates that decreased
      contractile and increased nicotine-induced relaxant response of the gastric
      smooth muscle in the surgically created GER model. These findings suggest that
      impaired gastric smooth muscle reactivity at least in part may play a role in
      gastric dysmotility in GER.

PMID- 14697295
TI  - Salvianolic acid B enhances in vitro angiogenesis and improves skin flap survival
      in Sprague-Dawley rats.
AB  - Insufficient angiogenesis and microcirculatory intravascular clotting have been
      implicated in the pathophysiology of skin flap failure. Salvianolic acid B (Sal
      B), isolated from Salvia miltiorrhiza, has been reported to enhance angiogenesis
      in vitro. This study was aimed to determine the efficacy of Sal B on ischemia
      reperfusion injury of the skin flap in Sprague-Dawley rats. Sal B was
      administered intraperitoneally 2 h before operation, and on the 2nd and 4th days
      after surgical elevation of an extended epigastric adipocutaneous flap (5 x 7 cm)
      in ketamine-anesthetized rats. Flap ischemia was achieved by ligating the right
      superficial epigastric artery and vein and clamping the left superficial
      epigastric artery and vein for 3 h and then released. Percentage of flap necrosis
      area (FNA) and plasma levels of aspartate aminotransferase, alanine
      aminotransferase, creatinine, and malondialdehyde were measured at 7 days after
      the operation. Animals were divided into six groups, including: vehicle, Sal B
      low dose (5 mg/kg), Sal B high dose (50 mg/kg) and each with [mesh(+)] or without
      mesh [mesh(-)] placement. In the three groups with mesh(+), FNA in control flaps
      was 53.7 +/- 6.9%, whereas low-dose and high-dose Sal B significantly improved
      flap survival with FNA 27.4 +/- 3.8% and 25.3 +/- 4.3%, respectively (P < 0.05,
      one-way ANOVA). In the three groups with mesh(-), control flaps were 35.9 +/-
      4.5%, whereas high-dose Sal B also significantly improved flap survival with FNA
      17.9 +/- 4.7% (P < 0.05, one-way ANOVA). There were no differences in aspartate
      aminotransferase, alanine aminotransferase, creatinine, or malondialdehyde
      between groups. We conclude that Sal B attenuates ischemia-reperfusion injury of
      skin flap, and provides therapeutic potential in reconstructive plastic surgery.

PMID- 14697296
TI  - The effects of gingko biloba extract (EGb 761) on experimental acute
      pancreatitis.
AB  - BACKGROUND AND OBJECTIVE: Acute pancreatitis is an important and fatal disease
      with high mortality and morbidity. Although the pathogenesis of acute
      pancreatitis is poorly understood, there are many studies that suggest the role
      for oxygen free radicals (OFRs) in the development of pancreatitis and its
      complications and show beneficial effects of scavenger treatment. In the present
      study, we aimed to investigate whether Egb761, the standardized extract of gingko
      biloba, restrains the generation of OFRs and ameliorates the histopathologic
      findings of acute pancreatitis. MATERIALS AND METHODS: Sixty male Sprague Dawley
      rats were randomly assigned to one of the following experimental groups. In early
      and late pancreatitis and treatment groups, acute pancreatitis was induced by
      retrograde infusion of 3% sodium taurocholate. In treatment groups, 100 mg/kg Egb
      761 was given intraperitoneally (IP) 24 h and immediately before induction of
      pancreatitis. Sham-operated rats received isotonic saline instead of sodium
      taurocholate. After observation times of 3.5 and 12 h, the pancreas was removed
      for light microscopy and determination of malondialdehyde (MDA) levels as a
      marker for OFRs-induced lipid peroxidation. Serum samples also were obtained for
      amylase and lipase levels. RESULTS: There was no significant difference in
      control and sham-operated groups in terms of histopathologic findings and serum
      enzyme levels. The tissue concentrations of MDA and serum enzyme levels were
      significantly elevated in early and late treatment groups as compared with the
      control group. The treatment with Egb 761 caused significant decrease in serum
      amylase and lipase levels and histopathologic scores as compared with early and
      late pancreatitis groups. CONCLUSIONS: Prophylactic application of Egb761 exerts
      highly beneficial influence on the course of acute pancreatitis, and this seems
      to be related to the oxygen radical scavenger effect of Egb761.

PMID- 14697297
TI  - Egr-1 in vascular smooth muscle cell proliferation in response to allo-antigen.
AB  - BACKGROUND: Early growth response factor-1 (Egr-1) plays an important role in
      regulating multiple factors involved in the progression of vascular lesions. This
      study examined our hypothesis that Egr-1 plays a critical role in the early stage
      of chronic cardiac allograft rejection and in the proliferation of the smooth
      muscle cell response to alloantigen. MATERIALS AND METHODS: Antisense Egr-1
      oligodeoxynucleotide (ODN) was ex vivo gene transfected into the donor hearts
      from DBA/2 mice, followed by heterotopic allografting into B10.D2 recipients. The
      allografts were harvested on day 30. Egr-1 and its target molecules, such as
      platelet-derived growth factor (PDGF)-A, basic fibroblastic growth factor (bFGF),
      vascular cell adhesion molecule (VCAM)-1, transforming growth factor (TGF)-beta
      and nonmuscle myosin heavy chain B (SMemb), were identified
      immunohistochemically, and the percentage of the lumen occluded by the intima was
      calculated. For the cell proliferation assay, sensitized T cells were harvested
      from B10.D2 recipients as stimulator and then added to the SMCs, which were
      harvested from DBA/2 mouse aorta. Cellular proliferation was measured and Egr-1
      and its target gene expression were examined by real-time RT-PCR. RESULTS: Egr-1
      and its target genes were expressed in the thickened intima from untreated
      recipients. Egr-1 antisense ODN inhibited not only Egr-1 expression but also its
      target genes and significantly suppressed intimal thickening of coronary
      arteries. Egr-1 antisense ODN also significantly inhibited cell proliferation and
      expressions of Egr-1 and Egr-1 target genes in a mixed cell culture model.
      CONCLUSION: We conclude that Egr-1 plays an important role in the formation of
      the cardiac allograft vasculopathy responding to alloantigens.

PMID- 14697298
TI  - Induction of cytokine tolerance requires internalization of Chylomicron-Bound LPS
      into hepatocytes.
AB  - BACKGROUND: Chylomicron-bound LPS (CM-LPS) renders hepatocytes unresponsive to
      stimulation by proinflammatory cytokines, a process termed cytokine tolerance. We
      have shown that cytokine tolerance is a time- and dose-dependent process
      requiring functional low-density lipoprotein receptors (LDLR). Thus, we
      hypothesized that cytokine tolerance directly correlates with the internalization
      of CM-LPS complexes, and inhibition of lipoprotein binding and/or internalization
      inhibits the induction of cytokine tolerance in hepatocytes. MATERIALS AND
      METHODS: We correlated the rate of internalization of radioiodinated CM-LPS
      complexes with hepatocellular NO production as a measure of cytokine
      responsiveness. In additional studies, we used four different strategies to
      inhibit binding/internalization of CM-LPS via LDLR and then determined the effect
      of each strategy on the induction of cytokine tolerance. RESULTS: There was a
      strong inverse correlation between the internalization of CM-LPS and the
      responsiveness of hepatocytes to proinflammatory cytokines (r(2) = -0.997).
      Furthermore, the greater the degree of LDLR inhibition, the less susceptible
      hepatocytes were to the induction of cytokine tolerance by CM-bound LPS.
      Accordingly, cytokine tolerance induction was inhibited in hepatocytes with
      decreased membrane expression of LDLR as compared to control cells (69 versus 12%
      control; P = 0.005). Competitive inhibition of CM-LPS binding prevented
      internalization of CM-LPS and resulted in loss of the cytokine-tolerant
      phenotype. Whereas CM-LPS successfully induced cytokine tolerance in ldlr(-/-)
      hepatocytes, it only occurred after a prolonged pretreatment period of 8 h. CM
      LPS complexes containing apolipoprotein (apo) E(2) also required a prolonged
      pretreatment period to induce a level of cytokine tolerance comparable to that
      induced by CM-LPS complexes containing either apo E(3) or E(4). CONCLUSION:
      Lipoprotein-bound LPS inhibits the responsiveness of hepatocytes to
      proinflammatory cytokines in a manner directly correlated with the
      internalization of LPS. Furthermore, inhibition of lipoprotein
      binding/internalization prevents this LPS-mediated induction of cytokine
      tolerance in rodent hepatocytes.

PMID- 14697299
TI  - Induction of heme oxygenase-1 and dilatation of hepatic sinusoids by an
      administration of pyrrolidine dithiocarbamate in rat livers.
AB  - INTRODUCTION: Inducing heme oxygenase-1 (HO-1) provides the liver with various
      protective effects against stressful conditions. In this article, we report our
      use of pyrrolidine dithiocarbamate (PDTC) to induce HO-1 in the liver in vivo and
      its impact on hepatic microcirculation. MATERIALS AND METHODS: PDTC was injected
      intramuscularly into rats and the expression of HO-1 in liver tissue was assessed
      by measuring both mRNA and protein levels. The distribution of induced HO-1 was
      evaluated immunohistochemically. The effect of PDTC administration on hepatic
      microcirculation was evaluated using intravital microscopy (IVM). Rats were
      divided into three groups: PDTC administration (group P), vehicle administration
      only (group C), and ZnPP-an inhibitor of HO-1-administration after PDTC treatment
      (group Z). Sinusoidal diameters were measured 24 h after the injections. RESULTS:
      PDTC administration induced HO-1 strongly in the liver, but not in other organs.
      HO-1 mRNA expression in liver tissue peaked 3 h after PDTC injection and then
      gradually decreased. The protein expression reached a maximum level at 24-48 h
      after the injection, and its expression was dose-dependent with PDTC.
      Immunohistochemistry revealed that HO-1 was induced not only in Kupffer cells,
      but also in hepatocytes in the pericentral area. IVM showed that in group P,
      sinusoidal diameters in zone 3 (21.94 +/- 1.29 microm) were twice as large as
      those in group C (11.14 +/- 0.28 microm, P < 0.0001). This dilation of sinusoids
      was completely reversed by ZnPP (10.95 +/- 0.37 microm, P < 0.0001). CONCLUSION:
      A single administration of PDTC induced HO-1 in the liver with remarkable
      sinusoidal dilation. PDTC administration, therefore, may be a useful, new
      strategy in place of other stress preconditioning.

PMID- 14697300
TI  - Regulation of murine endogenous retroviruses in the thymus after injury.
AB  - We recently reported the induction of murine endogenous retroviruses (murine AIDS
      related) in several distant organs of mice after burn injury. The regulation of
      endogenous retroviruses in response to burn injury was further investigated in
      the thymus. Female C57BLKS/J mice were subjected to 18% total body surface area
      flame burn injury. Thymus tissues collected at several time points (3 h to 7
      days) were analyzed for the expression of subgenomic transcripts of murine
      endogenous retroviruses by RT-PCR. Interestingly, a novel 1.7-Kb subgenomic
      transcript and a recently described 1.1 Kb subgenomic transcript of murine
      endogenous retroviruses were transiently down-regulated in the thymus at day 1
      after injury. The 1.7 Kb transcript has a coding potential for a truncated form
      of the envelope protein (total 214 amino acids) with a deletion of 418 amino
      acids near the C-terminus. The second transcript of 1.1 Kb has an open reading
      frame for the C-terminal transmembrane domain of the envelope protein including
      the p2E protein (R peptide). These data suggest the pathophysiologic effects of
      burn injury on the differential expression of murine endogenous retroviruses in
      the thymus after injury.

PMID- 14697301
TI  - The role of estrogen in cardiovascular disease.
AB  - Cardiovascular disease is the number one cause of death among women, accounting
      for nearly 50% of female deaths. Statistics show that women on average develop
      cardiovascular disease 10 to 15 years later in life than men, and that the risk
      may increase after menopause. This observation has led to much speculation as to
      what physiological change(s) associated with menopause is responsible for the
      higher risk of atherosclerosis. Estrogen, with its potential as a
      cardioprotective agent and as an immunomodulator of the inflammatory response in
      atherosclerosis, has received the most attention. Understanding the mechanisms
      that lead to these differences may allow beneficial therapeutic intervention to
      enhance this effect in females and evoke this protection in males. This review
      will do the following: (1) characterize mechanisms of atherosclerosis, (2)
      explore the role of estrogen-replacement therapy, (3) define the effect of gender
      on inflammation, (4) compare and contrast the effects of estrogen and
      testosterone on endothelial functional, and (5) suggest mechanistic based
      therapeutic opportunities.

PMID- 14697302
TI  - Cloning and sequencing of the FSH-beta and LH beta-subunit in the three-spined
      stickleback, Gasterosteus aculeatus, and effects of photoperiod and temperature
      on LH-beta and FSH-beta mRNA expression.
AB  - The aim of this study was to characterize the FSH-beta and LH-beta subunit in the
      three-spined stickleback, a fish used extensively in experimental studies, and to
      use the cloned cDNAs as probes for measuring FSH-beta and LH-beta mRNA expression
      in sticklebacks treated with different photoperiods and temperatures. A first
      strand cDNA was prepared from 10 pituitaries from male sticklebacks, and cDNA
      fragments were amplified by PCR using degenerated primers based on highly
      conserved regions of known teleost FSH-beta and LH-beta cDNA sequences. To obtain
      full-length cDNAs of FSH-beta and LH-beta, RACE amplifications were performed.
      The cDNA of FSH-beta was 540 bp long, encoding a protein of 122 amino acids and
      LH-beta cDNA was 568 bp long, encoding a protein of 148 amino acids. Of
      gonadotropin (GTH) beta-subunits published so far, those most similar to
      stickleback GTHs are found among other percomorph fishes, with amino acid
      similarities of 46-55% for FSH-beta and 75-77% for LH-beta subunits.The cloned
      cDNAs were used as probes to analyze LH and FSH mRNA expression in pituitaries
      from sticklebacks exposed to different photoperiods and temperatures. Two hundred
      males were divided into four groups and kept under different photoperiods and
      temperatures; light:dark (LD) 16:8, 20 degrees C; LD 16:8, 7 degrees C; LD 8:16,
      20 degrees C, and LD 8:16, 7 degrees C. Red breeding colors and a marked kidney
      hypertrophy, androgen-dependent male secondary sexual characters in the
      stickleback, appeared in the group kept under LD 16:8 at 20 degrees C, but not in
      the other groups. The kidney epithelium height (KEH) was significantly lower in
      the LD 8:16, 20 degrees C group than in all other groups, and this was also the
      only group with active spermatogenesis. The LD 8:16 20 degrees C had
      significantly lower expression of both FSH-beta and LH-beta than all other
      groups. Thus, both GTHs displayed their lowest expression when spermatogenesis
      was active and when low KEH indicated that androgens levels were at their lowest.

PMID- 14697303
TI  - Hormonal correlations at transition from reproduction to molting in an annual
      life cycle of Humboldt penguins (Spheniscus humboldti).
AB  - To understand the hormonal mechanism behind a unique strategy of breeding and
      molting in Humboldt penguins, six pairs of captive Humboldt penguins kept in an
      outdoor open display pen were observed and blood collected weekly for a year.
      They all molted between the middle of June and the middle of August within 10
      days except one pair that molted about a month later. The late pair had been
      rearing a hatchling until July due to the successful second clutch after the
      first clutch failed. A peak of plasma levels of thyroxine and triiodothyronine,
      respectively, overlapped a period of molting in both sexes. Plasma testosterone
      concentrations in the males and females were lowest for two month during a period
      of pre-molt and molting. Plasma concentrations of estradiol were also lowest
      during the molt in both sexes. Except for the period of molting, sex steroid
      hormone concentrations were high although there was great individual variation.
      During the molt, the birds were forced to fast since they did not enter the pool
      in the display pen where they usually forage live fish. To compensate this forced
      fasting, they took more food than usual during pre-molting period and gained body
      mass to about 20% more than the baseline value. Increased flipper thickness was
      parallel to increased body mass indicating that the gained body mass attributed
      to fat reservoir. These data indicate that rapid molting in Humboldt penguins is
      correlated with a drastic increase and decrease of thyroid hormones during the
      period of lowest concentrations in sex steroid hormones.

PMID- 14697304
TI  - Localization of orexin-A-like immunoreactivity in prolactin cells in the bullfrog
      (Rana catesbeiana) pituitary.
AB  - Immunohistochemical techniques were employed to investigate the distribution of
      orexin-A-like immunoreactivity in the bullfrog (Rana catesbeiana) pituitary.
      Orexin-A-immunoreactive cells were scattered throughout the pars distalis. We
      found that these cells corresponded to the cells immunostained with antiserum
      against bullfrog prolactin (fPRL). Immunoelectron microscopic analysis indicated
      that an orexin-A-like substance coexisted with fPRL within secretory granules.
      Western blot analysis of bullfrog pituitary extract revealed that anti-human
      orexin-A antiserum labeled two separate bands which were not labeled with anti
      fPRL antiserum. The present study has, for the first time, provided evidence of
      the intragranular colocalization of orexin-A-like and PRL immunoreactivities in
      the bullfrog pituitary.

PMID- 14697305
TI  - Seasonal changes in adrenocortical responses to acute stress in polygynous male
      bush warblers (Cettia diphone).
AB  - The adrenocortical response to acute stress as measured by increase in plasma
      levels of corticosterone following capture, handling, and restraint over an hour
      was estimated in free-living male bush warblers at different times of the
      breeding season on their breeding ground in Chichibu, Honshu, Japan. Initial
      plasma levels of corticosterone showed a seasonal change, being moderate in
      April, highest in May to July and declined in late August. In contrast, the
      stress response was suppressed at the early stage of the breeding season, April
      and May, and just after the breeding season, late August. In June, July, and
      early August, the response was obvious although the initial levels of
      corticosterone were high. These results are different from those of monogamous
      passerine birds so far studied in which adrenocortical response is obvious at the
      early stage of breeding season and the response is suppressed later stage when
      the male is involved in parental care. The results suggest that during a course
      of the breeding season, male bush warblers that take a polygynous breeding
      strategy may decrease the amplitude of the adrenocortical response to acute
      stress at the early stage of the breeding season so as to allow establishment and
      defense of a territory. The birds became more sensitive to acute stress later the
      breeding season when they already had females incubating, feeding hatchlings or
      even fledgling. This change of stress response is likely to be a reflection of
      polygynous breeding strategy of the species.

PMID- 14697306
TI  - Effects of iodothyronines on the hepatic outer-ring deiodinating pathway in
      killifish.
AB  - Substrate availability has been thought to be a major regulator of the outer-ring
      deiodinating pathway (ORD) in fish. However, current information strongly
      suggests that while fish iodothyronine deiodinase type 2 (D2) responds to
      iodothyronines in the same manner as its mammalian counterpart, fish deiodinase
      type 1 (D1) exhibits a distinct response. Furthermore, 3,5-T2, generally
      considered to be an inactive product of iodothyronine metabolism, has recently
      been described as bioactive, but its effects upon D1 and D2 are not yet known. We
      examined the effect that short-term immersion in T4, T3, and 3,5-T2 (0.1 microM;
      12 or 24 h) exerts on both D1 and D2 activities and on the levels of expression
      of D1 and D2 mRNAs in killifish liver. In agreement with previous reports in
      teleosts, no iodothyronine exerted a significant effect on D1 enzymatic activity.
      However, all three iodothyronines significantly decreased D2 activity.
      Furthermore, at 24 h post-immersion T4, T3, and 3,5-T2 inhibited both D1 and D2
      transcription. Together, the present results confirm the differential effect of
      iodothyronines upon the hepatic ORD pathway in fish and show that this effect can
      occur at a transcriptional level. Furthermore, we provide the first evidence that
      3,5-T2 can affect both activity and transcription of hepatic deiodinases in
      teleosts.

PMID- 14697307
TI  - Short-term responses of coronary circulation to cortisol and estrogen in trout
      (Oncorhynchus mykiss).
AB  - This study was designed to investigate the short-term effects of cortisol and 17
      beta-estradiol on the intact coronary tree of rainbow trout (Oncorhynchus
      mykiss). A non-working, isolated, and perfused heart preparation was used. The
      coronary pressure was monitored together with the coronary flow in order to
      calculate the coronary resistance. The drug effects were expressed as percent
      change in coronary resistance. At concentrations higher than 10(-5) mol l(-1),
      cortisol elicited a significant vasoconstriction (p<0.001) within 10 min of
      perfusion. The simultaneous administration of cortisol and adenosine (both at 10(
      4) mol l(-1)) induced a significant reduction (p<0.001) of the coronary tree
      response elicited by each drug alone. The perfusion of the intact coronary trout
      system with 20 ng ml(-1) of 17-beta-estradiol elicited a significant vasodilative
      response (p<0.001) within 5-15 min of perfusion. This vasodilation did not
      involve nitric oxide, because no significant effect of Nomega-nitro-L-arginine (L
      NA, a nitric oxide synthase inhibitor) in presence of the estrogen was observed.
      17-beta-estradiol was also able to reduce the vasoconstriction induced by 10(-3)
      mol l(-1) acetylcholine. From these results it is possible to suggest that the
      steroid hormones, cortisol and 17-beta-estradiol, expound their action on the
      trout coronary tree through a non-genomic mechanism.

PMID- 14697308
TI  - Rapid suppression of testosterone secretion after capture in male American
      alligators (Alligator mississippiensis).
AB  - All reptiles studied to date show an increase in circulating corticosterone
      following capture. This rise in corticosterone has also been shown in a number of
      instances to result in a decline in reproductive steroids within hours after
      capture. As a result of these observations it has been considered imperative to
      collect blood samples as soon as possible after capture to get reliable measures
      of reproductive hormones. It has been claimed, however, that there is no effect
      of capture stress on reproductive steroids in juvenile alligators held for 2 h
      following capture. As we generally reject blood samples that are not collected
      within 15 min of capture we decided to reinvestigate the effect of short-term
      capture (2 h) on corticosterone and testosterone in male alligators. Four groups
      of alligators, ranging in size from 74 to 212 cm total length were captured in a
      2-week period in May, the time of year when testosterone levels are highest. Two
      groups were captured during the day (eight bled at capture and again at 2 h,
      eight bled at 2 h only) and two at night (10 bled at capture and again at 2 h, 10
      bled at 2 h only). Testosterone and corticosterone in alligators bled immediately
      on capture and at 2 h were not significantly different in the AM and PM samples
      so the results were combined (Initial bleed: corticosterone, 0.95 +/- 0.09 ng/ml,
      n=18; testosterone, 6.06 +/- 2.09 ng/ml, n=18. Two-hour bleed: corticosterone
      15.68 +/- 1.91, n=18; testosterone, 2.75 +/- 0.79, n=18). Both the increase in
      corticosterone and the decline in testosterone at 2 h were significant (p<0.05).
      Corticosterone and testosterone in the alligators sampled only once at 2 h were
      not significantly different from the 2-h values in alligators sampled twice
      (corticosterone 15.04 +/- 1.29, n=18; testosterone, 1.85 +/- 0.62, n=18). These
      results clearly demonstrate that short-term capture stress results in a
      significant decline in testosterone in male alligators.

PMID- 14697309
TI  - The effects of combined aromatase inhibitor and anti-androgen on male territorial
      aggression in a tropical population of rufous-collared sparrows, Zonotrichia
      capensis.
AB  - Territorial aggression, exhibited by male vertebrates in a reproductive context,
      is generally thought to be mediated by elevated levels of the gonadal steroid
      hormone testosterone. Rufous-collared sparrows from Papallacta, Ecuador are only
      aggressive during the breeding season when plasma testosterone concentrations are
      elevated. However, previous experiments have determined that during the breeding
      season testosterone does not increase in response to territorial challenges and
      testosterone implants do not make males more aggressive. This relationship
      between testosterone and aggression is different from closely related northern
      latitude species. We conducted another experiment investigating the role of
      testosterone in mediating territorial aggression, during the breeding season, in
      male rufous-collared sparrows. We predicted that blocking the actions of the
      testosterone would suppress aggression in response to territorial challenges.
      During the early breeding season males were captured using a simulated
      territorial intrusion and there was no relationship between time to capture and
      plasma testosterone, dihydrotestosterone, and corticosterone concentrations.
      Individual males were then implanted with both the aromatase inhibitor ATD and
      the anti-androgen Flutamide or empty implants as a control. After one week, birds
      were challenged with a simulated territorial intrusion and the aggressive
      responses measured. There were no differences in individual behavioral responses
      (number of songs, flights, closest approach, or time within 5 m) or overall
      aggression between the two groups. Androgen levels were elevated, post-implant,
      in the experimental group suggesting that the treatment was successful by
      blocking the negative feedback system. We conclude that pharmacologically
      inhibiting testosterone during the breeding season does not affect territorial
      aggression in these birds.

PMID- 14697310
TI  - Effects of cortisol on food intake, growth, and forebrain neuropeptide Y and
      corticotropin-releasing factor gene expression in goldfish.
AB  - Although elevated plasma cortisol levels and a reduction in food intake are
      common features of the response to stress in fish, the potential role of cortisol
      in the regulation of food intake in these animals is poorly understood. In this
      study, goldfish (Carassius auratus) were fed ad libitum for 21 days diets
      prepared to contain 0 (Control), 50 (Low) or 500 (High) microg cortisol/g of
      food. While feeding remained unchanged in controls and in fish fed the High
      cortisol diet, daily food intake gradually increased in the Low cortisol diet
      group and was significantly elevated between days 9 and 21. At the end of the
      feeding trial, specific growth rate was lowest in fish fed the High cortisol
      diet, intermediate in those fed the Low cortisol diet, and highest in the
      controls. Feed conversion efficiency, on the other hand, was significantly
      reduced in both groups of fish fed the cortisol diets. After 3 weeks on the diets
      and relative to controls, the Low cortisol diet group was characterized by a 34%
      increase in neuropeptide Y (NPY) and a 22% decrease in corticotropin-releasing
      factor (CRF) mRNA levels in the telencephalon-preoptic brain region. In contrast,
      the High cortisol diet group was characterized by a 46% decrease in CRF mRNA
      levels and no significant change in NPY gene expression. In a separate
      experiment, intraperitoneal implants of cortisol (150 and 300 microg cortisol/g
      body weight) elicited a dose-dependent increase in NPY and decrease in CRF mRNA
      levels in the telencephalon-preoptic region at 72 h post-treatment. These results
      show that while moderate increases in plasma cortisol can stimulate food intake
      slowly over days, larger catabolic doses of glucocorticoids may mask the appetite
      stimulatory effects of cortisol. Therefore, excess cortisol in goldfish can be
      associated with poor growth despite normal food intake. Furthermore, our results
      indicate that forebrain NPY and CRF may play a role in mediating the effects of
      cortisol on food intake in goldfish.

PMID- 14697311
TI  - Cloning of zebrafish ovarian P450c17 (CYP17, 17alpha-hydroxylase/17, 20-lyase)
      and characterization of its expression in gonadal and extra-gonadal tissues.
AB  - Cytochrome P450c17 (CYP17, 17alpha-hydroxylase/17, 20-lyase) has been viewed as a
      critical enzyme for the biosynthesis of gonadal and adrenal steroids in
      vertebrates. A full-length cDNA coding for P450c17 has been cloned from the
      zebrafish ovary. It encodes 519 amino acids and shares high sequence identity
      with that of fathead minnow (92%), rainbow trout (74%), chicken (64%), rat (47%),
      and human (48%). Northern blot analysis demonstrated that it is predominantly
      expressed in the ovary and testis; however, a weak hybridization signal was also
      detected in the whole kidney of the zebrafish, suggesting a role for P450c17 in
      the steroidogenesis of both gonads and renal/interrenal tissues. We further
      examined the expression of P450c17 in the developing ovarian follicles. Northern
      analysis and RT-PCR revealed abundant expression of the enzyme in the follicles
      of all major stages including pre-vitellogenic, vitellogenic and post
      vitellogenic full-grown follicles; however, unlike P450c17 in the rainbow trout
      and eel, the expression of zebrafish P450c17 did not show significant temporal
      difference among different developmental stages, similar to the finding in the
      fathead minnow. The constitutive nature of P450c17 expression during zebrafish
      follicle development may partly explain the poor transcriptional response of the
      enzyme to the treatments with gonadotropin or activin, both of which enhance
      oocyte maturation in this species. It is also of interest to note that when
      assayed by RT-PCR, the enzyme P450c17 also seemed to be expressed in several
      other non-gonadal tissues including the brain, gill, liver and intestine, and its
      expression did not show significant sexual dimorphism in the brain of adult
      zebrafish. The physiological relevance of these findings remains to be further
      elucidated.

PMID- 14697312
TI  - Primary structure of stanniocalcin in two basal Actinopterygii.
AB  - The primary structure of stanniocalcin (STC), the principal product of the
      corpuscles of Stannius (CS) in ray-finned fishes, was deduced from STC cDNA
      clones for two species of holostean, the gar, Lepisosteus osseus and the bowfin,
      Amia calva. Overlapping partial cDNA clones were amplified by polymerase chain
      reaction (PCR) from single-strand cDNA of the CS. Excluding the poly(A) tail, the
      cDNAs of 1863 base pairs [bp] (gar) and 914 bp (bowfin) contained the 5'
      untranslated region followed by the coding region and the 3' untranslated region.
      Both the gar and bowfin STC cDNA encode a prehormone of 252 amino acids (aa) with
      a signal peptide of 32 aa and a mature protein of 220 aa. The deduced aa sequence
      of gar STC shows 87% identity with bowfin STC, 60-72% identity with most
      vertebrate STCs and 26% identity with mouse STC2. Phylogenetic analysis of the
      sequences support a view that the gar and bowfin form a monophyletic holostean
      clade. RT-PCR revealed in the gar and bowfin that, just as in mammals and rainbow
      trout, the expression of STC mRNA is widely spread in many tissues and organs.
      Since the gar and bowfin are representatives of the most ancient fishes known to
      possess CS, the corpuscular-derived STC molecule in fish has had a conserved
      evolution.

PMID- 14697313
TI  - The potential of GDNF as a treatment for Parkinson's disease.

PMID- 14697314
TI  - Survival of neuronal tissue following xenograft implantation into the adult rat
      inner ear.
AB  - The poor regenerative capacity of the spiral ganglion neurons of the mammalian
      inner ear has initiated research on how to assist the functional recovery of the
      injured auditory system. A possible treatment is to use a biological implant with
      a potential to establish central or peripheral synaptic contacts to develop into
      a functional auditory unit. The feasibility of this approach was tested by
      xenograft implantation of dorsal root ganglion (DRG) neurons from embryonic days
      13 to 14, mouse expressing either LacZ or enhanced green fluorescent protein
      (EGFP) into the scala tympani of the adult rat inner ear. Transplanted DRG
      neurons survived in the scala tympani for a postoperative period ranging from 3
      to 10 weeks, as verified by histochemical detection of LacZ, EGFP fluorescence
      and immunohistochemical labeling of the neuronal markers neurofilament and Thy
      1.2. DRG neurons were found close to structures near the sensory epithelium (the
      organ of Corti) as well as adjacent to the spiral ganglion neurons with their
      peripheral dendrites. These results illustrate not only the survival of
      xenografted DRG neurons in the adult inner ear but also the feasibility of a
      neuronal transplantation strategy in the degenerated auditory system, thereby
      creating possibilities to replace spiral ganglion neurons.

PMID- 14697315
TI  - Olfactory ensheathing cells promote collateral axonal branching in the injured
      adult rat spinal cord.
AB  - In recent years, injection of olfactory ensheathing cells (ECs) into the spinal
      cord has been used as an experimental strategy to promote regeneration of injured
      axons. In this study, we have compared the effects of transplanting encapsulated
      ECs with those injected directly into the spinal cord. The dorsal columns of
      adult rats were cut at T(8-9) and rats in experimental groups received either EC
      filled porous polymer capsules or culture medium (CM)-filled capsules with ECs
      injected at the injury site. Control rats were in three groups: (1) uninjured,
      (2) lesion with transplantation of CM-filled capsules and (3) lesion with
      transplantation of CM-filled capsules and injections of CM. Three weeks after
      injury, Fluororuby was injected into the hindlimb motor and somatosensory cortex
      to label corticospinal neurons. Observations indicated that there were a few
      regenerating fibres, up to 10, in the EC-treated groups. In rats that received
      encapsulated ECs, regenerating fibres were present in close association with the
      capsule. Rats that received EC injections demonstrated a significant increase in
      the number of collateral branches from the intact ventral corticospinal tract
      (vCST) compared with the corresponding control, CM-injected group (P=0.003),
      while a trend for increased collateral branches was observed in rats that
      received encapsulated ECs (P=0.07).

PMID- 14697316
TI  - Long-term lentiviral-mediated expression of ciliary neurotrophic factor in the
      striatum of Huntington's disease transgenic mice.
AB  - Ciliary neurotrophic factor (CNTF) has been shown to prevent behavioral deficits
      and striatal degeneration in neurotoxic models of Huntington's disease (HD), but
      its effect in a genetic model has not been evaluated. Lentiviral vectors
      expressing the human CNTF or LacZ reporter gene were therefore injected in the
      striatum of wild-type (WT) and transgenic mice expressing full-length huntingtin
      with 72 CAG repeats (YAC72). Behavioral analysis showed increased locomotor
      activity in 5- to 6-month-old YAC72-LacZ mice compared to WT-LacZ animals.
      Interestingly, CNTF expression reduced the activity levels of YAC72 mice compared
      to control animals. In both WT and YAC72 mice, CNTF expression was demonstrated
      in striatal punches, up to a year after lentiviral injection. Stereological
      analysis revealed that the number of LacZ and DARPP-32-positive neurons were
      decreased in YAC72-LacZ mice compared to WT-LacZ animals. Assessment of the
      benefit of CNTF expression in the YAC72 mice was, however, complicated by a down
      regulation of DARPP-32 and to a lesser extent of NeuN in all mice treated with
      CNTF. The expression of the neuronal marker NADPH-d was unaffected by CNTF, but
      expression of the astrocytic marker glial fibrillary acidic protein (GFAP) was
      increased. Finally, a reduction of the number of striatal dark cells was observed
      in YAC mice treated with CNTF compared to LacZ. These data indicate that
      sustained striatal expression of CNTF can be achieved with lentiviruses. Further
      studies are, however, needed to investigate the intracellular signaling pathways
      mediating the long-term effects of CNTF expression on dopamine signaling, glial
      cell activation and how these changes may affect HD pathology.

PMID- 14697317
TI  - Ropinirole versus L-DOPA effects on striatal opioid peptide precursors in a
      rodent model of Parkinson's disease: implications for dyskinesia.
AB  - The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), remains the most
      common treatment for Parkinson's disease. However, following long-term treatment,
      disabling side effects, particularly L-DOPA-induced dyskinesias, are encountered.
      Conversely, D2/D3 dopamine receptor agonists, such as ropinirole, exert an anti
      parkinsonian effect while eliciting less dyskinesia when administered de novo in
      Parkinson's disease patients. Parkinson's disease and L-DOPA-induced dyskinesia
      are both associated with changes in mRNA and peptide levels of the opioid peptide
      precursors preproenkephalin-A (PPE-A) and preproenkephalin-B (PPE-B).
      Furthermore, a potential role of abnormal opioid peptide transmission in
      dyskinesia is suggested due to the ability of opioid receptor antagonists to
      reduce the L-DOPA-induced dyskinesia in animal models of Parkinson's disease. In
      this study, the behavioural response, striatal topography and levels of
      expression of the opioid peptide precursors PPE-A and PPE-B were assessed,
      following repeated vehicle, ropinirole, or L-DOPA administration in the 6-OHDA
      lesioned rat model of Parkinson's disease. While repeated administration of L
      DOPA significantly elevated PPE-B mRNA levels (313% cf. vehicle, 6-OHDA-lesioned
      rostral striatum; 189% cf. vehicle, 6-OHDA-lesioned caudal striatum) in the
      unilaterally 6-OHDA-lesioned rat model of Parkinson's disease, ropinirole did
      not. These data and previous studies suggest the involvement of enhanced opioid
      transmission in L-DOPA-induced dyskinesia and that part of the reason why D2/D3
      dopamine receptor agonists have a reduced propensity to elicit dyskinesia may
      reside in their reduced ability to elevate opioid transmission.

PMID- 14697318
TI  - MPTP potentiates 3-nitropropionic acid-induced striatal damage in mice: reference
      to striatonigral degeneration.
AB  - Striatonigral degeneration (SND) is a parkinsonian disorder due to the combined
      degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc)
      and striatal output neurons. The aims of this study were to explore (1) the
      behavioral and histopathological consequences of combined MPTP plus 3
      nitropropionic acid (3-NP) intoxication in C57/Bl6 mice and (2) its ability to
      reproduce the neuropathological hallmarks of SND. 3-NP was administered i.p.
      every 12 h (total dose=450 mg/kg in 9 days) and MPTP i.p. at 10 mg/(kg day)
      (total dose=90 mg/kg in 9 days). Four groups of mice (n=10) were compared:
      control, 3-NP alone, MPTP alone, MPTP + 3-NP. Mice intoxicated with 3-NP and MPTP
      + 3-NP developed motor symptoms, including hindlimb dystonia and clasping,
      truncal dystonia and impaired balance adjustments. The severity of motor disorder
      was worse and lasted longer in MPTP + 3-NP-treated mice compared to 3-NP alone,
      MPTP alone and controls. 3-NP and MPTP + 3-NP-treated mice also displayed altered
      gait patterns, impaired motor performance on the pole test, rotarod and
      traversing a beam tasks and activity parameters. Several of these sensorimotor
      deficits were also more severe and lasted longer in MPTP + 3-NP-treated mice.
      Histology demonstrated increased neuronal loss along with astrocytic activation
      (glial fibrillary acid protein, GFAP) and a higher incidence of circumscribed
      striatal lateral lesions in MPTP + 3-NP-treated mice compared to 3-NP. Neuronal
      loss and astrocytic activation were increased in the lateral part of the striatum
      in 3-NP-intoxicated mice while observed both in the medial and lateral part in
      MPTP + 3-NP-intoxicated mice. There was also a significant loss of SNc
      dopaminergic neurons and striatal terminals, similar to that in MPTP-treated
      mice. Altogether, these results suggest that MPTP potentiates striatal damage and
      behavioral impairments induced by 3-NP intoxication in mice and constitutes a
      useful model of the motor disorder and its histopathological correlates in SND.

PMID- 14697319
TI  - Impact of the selective estrogen receptor modulator, raloxifene, on neuronal
      survival and outgrowth following toxic insults associated with aging and
      Alzheimer's disease.
AB  - The current study investigated the estrogen agonist-antagonist properties of the
      selective estrogen receptor modulator, raloxifene (Ral), on neuroprotection and
      neuronal markers of memory function. Low concentrations of raloxifene
      significantly reduced basal markers of membrane damage and had no deleterious
      effect on neuronal survival. However, high concentrations of raloxifene (1000
      5000 ng/ml) induced a significant increase in markers of membrane damage and a
      significant decrease in neuronal survival. At subtoxic concentrations, raloxifene
      induced significant neuroprotection against beta amyloid(25-35)-, hydrogen
      peroxide- and glutamate-induced toxicity. Results of analyses to determine
      whether raloxifene acted competitively or synergistically with 17 beta-estradiol
      revealed that a postmenopausal level of 17 beta-estradiol exerted a significantly
      greater increase in neuronal survival against beta-amyloid- and glutamate-induced
      toxicity compared to 50 ng/ml raloxifene. The combined presence of raloxifene and
      17 beta-estradiol was significantly neuroprotective against beta amyloid(25-35)-
      and glutamate-induced excitotoxicity but was significantly lower than 17 beta
      estradiol alone while not significantly different than raloxifene alone.
      Morphologic analyses demonstrated that raloxifene significantly increased
      neuronal outgrowth of hippocampal neurons within a narrow dose range that was
      blocked by a glutamate NMDA receptor antagonist. Raloxifene did not promote the
      outgrowth of basal forebrain or cortical neurons. Results of this study indicate
      that raloxifene exerted partial estrogen agonist action in the absence of 17 beta
      estradiol whereas in the presence of 17 beta-estradiol, raloxifene exerted a
      mixed estrogen agonist-antagonist effect.

PMID- 14697320
TI  - Mediators of ischemic preconditioning identified by microarray analysis of rat
      spinal cord.
AB  - Spinal ischemia is a frequent cause of paralysis. Here we explore the biological
      basis of ischemic preconditioning (IPC), the phenomenon in which a brief period
      of ischemia can confer protection against subsequent longer and normally
      injurious ischemia, to identify mediators of endogenous neuroprotection. Using
      microarrays, we examined gene expression changes induced by brief spinal ischemia
      using a rat balloon occlusion model. Among the nearly 5000 genes assayed,
      relatively few showed two-fold changes, and three groups stood out prominently.
      The first group codes for heat shock protein 70, which is induced selectively and
      robustly at 30 min after brief ischemia, with increases up to 100-fold. A second
      group encodes metallothioneins 1 and 2. These mRNAs are increased at 6 and 12 h
      after ischemia, up to 12-fold. The third group codes for a group of immediate
      early genes not previously associated with spinal ischemia: B-cell translocation
      gene 2 (BTG2), the transcription factors early growth response 1 (egr-1) and
      nerve growth factor inducible B (NGFI-B), and a mitogen-activated protein kinase
      phosphatase, ptpn16, an important cell signaling regulator. These mRNAs peak at
      30 min and return to baseline or are decreased 6 h after ischemia. Several other
      potentially protective genes cluster with these induced mRNAs, including small
      heat shock proteins, and many have not been previously associated with IPC. These
      results provide both putative mediators of IPC and molecular targets for testing
      preconditioning therapies.

PMID- 14697321
TI  - Characterization of spinal HSP72 induction and development of ischemic tolerance
      after spinal ischemia in rats.
AB  - Induction of heat shock protein (HSP72) has been implicated in the development of
      ischemic tolerance in several tissue organs including brain and spinal cord. In
      the present study, using an aortic balloon occlusion model in rats, we
      characterized the effect of transient noninjurious (3 or 6 min) or injurious
      intervals (10 min) of spinal ischemia followed by 4-72 h of reflow on spinal
      expression of HSP72 and GFAP protein. In a separate group of animals, the effect
      of ischemic preconditioning (3 or 6 min) on the recovery of function after
      injurious interval of spinal ischemia (10 min) was studied. After 3 min of
      ischemia, there was a modest increase in HSP72 protein immunoreactivity in the
      dorsal horn neurons at 12 h after reperfusion. After 6 min of ischemia, a more
      robust and wide spread HSP72 protein expression in both dorsal and ventral horn
      neurons was detected. The peak of the expression was seen at 24 h after ischemia.
      At the same time point, a significant increase in spinal tissue GFAP expression
      was measured with Western blots and corresponded morphologically with the
      presence of activated astrocytes in spinal segments that had been treated
      similarly. After 10 min of ischemia and 24 h of reflow, a significant increase in
      spinal neuronal HSP72 expression in perinecrotic regions was seen. Behaviorally,
      3 min preconditioning ischemia led to the development of a biphasic ischemic
      tolerance (the first at 30 min and the second at 24 h after preconditioning) and
      was expressed as a significantly better recovery of motor function after exposure
      to a second 10-min interval of spinal ischemia. After 6 min ischemic
      preconditioning, a more robust ischemic tolerance at 24 h after preconditioning
      then seen after 3-min preconditioning was detected. These data indicate that 3
      min of spinal ischemia represents a threshold for spinal neuronal HSP72
      induction, however, a longer sublethal interval (6 min) of preconditioning
      ischemia is required for a potent neuronal HSP72 induction. More robust
      neurological protection, seen after 6 min of preconditioning ischemia, also
      indicates that HSP72 expression in spinal interneurons seen at 24 h after
      preconditioning may represent an important variable in modulating ischemic
      tolerance observed during this time frame.

PMID- 14697322
TI  - The dual response of protein kinase Fyn to neural trauma: early induction in
      neurons and delayed induction in reactive astrocytes.
AB  - In the developing central nervous system, a src-related protein-tyrosine kinase
      fyn participates in the myelination process, neuronal growth, and cytoskeletal
      organization. In adults, fyn has been implicated in learning and memory
      formation. To test if fyn expression is modulated by neuronal activity, we
      performed quantitative in situ hybridization (ISH) using brain sections of the
      adult rats that had undergone either kainic acid (KA)-induced seizures or
      neuronal deafferentation (entorhinal cortex lesion, ECL). In the KA model, a few
      hours after seizure activities, fyn mRNA was elevated in the dentate gyrus (DG)
      (+45%), cerebral cortex layer III (+35%), and piriform cortex (+25%). Conversely,
      fyn mRNA consistently decreased in the hippocampal neurons after transection of
      the major axonal inputs from the entorhinal cortex. Although fyn expression in
      the brain has been allegedly limited to neurons and oligodendrocytes, we provide
      in this study the first evidence that fyn mRNA is highly expressed in the
      astrocytes involved in reactive gliosis. In the KA model, the occurrence of fyn
      overexpressing astrocytes increased with the progress of neuronal damage in the
      CA1 and CA3 regions of the hippocampus. In contrast, fyn-overexpressing
      astrocytes were not observed in the granular cell layer of dentate gyrus (DG),
      where neurons were not damaged. Likewise, in the ECL model, the most drastic
      change in fyn mRNA expression took place at the reactive astrocytes near the stab
      wound sites, where fyn mRNA levels were doubled 4-10 d after the lesion.
      Collectively, our data suggest that (i) an early induction of fyn mRNA in neurons
      is linked to neuronal activity, and (ii) the delayed induction of fyn mRNA in
      reactive astrocytes near the damaged cells may play novel signaling roles during
      glial response.

PMID- 14697323
TI  - Injury severity and cell death mechanisms: effects of concomitant hypovolemic
      hypotension on spinal cord ischemia-reperfusion in rats.
AB  - A number of previous studies indicated that ischemia-reperfusion injury causes
      two distinct types of cell death--necrosis and apoptosis--in the central nervous
      system. It was also implicated that the intensity of injury can somehow affect
      the cell death mechanisms. By occluding the descending thoracic aorta with or
      without simultaneously induced hypovolemic hypotension in rats, we established a
      model of experimental spinal cord ischemia-reperfusion (I/R) in which the injury
      severity can be controlled. Recordings of carotid blood pressure (CBP) and spinal
      cord blood flow (SCBF) showed that aortic occlusion induced dramatic CBP
      elevation but SCBF drop in both the normotensive (NT) and hypotensive (HT) groups
      of rats. However, the HT group demonstrated significantly lower SCBF during
      aortic occlusion, and much slower elevation of SCBF after reperfusion, and
      extremely poor neurological performance. Spinal cord lesions were characterized
      by infarction associated with extensive necrotic cell death, but little apoptosis
      and caspase-3 activity. In contrast, in the NT group, I/R injury resulted in
      minor tissue destruction associated with persistent abundant apoptosis, augmented
      caspase-3 activity, and favorable functional outcome. The relative sparing of
      motoneurons in the ventral horns from apoptosis might have accounted for the
      minor functional impairment in the NT group. The severity of I/R injury was found
      to have substantial impact on the histopathological changes and cell death
      mechanisms, which correlate with neurological performance. Our results implicate
      that injury severity and duration after injury are two critical factors to be
      considered in therapeutic intervention.

PMID- 14697324
TI  - Improved neural progenitor cell survival when cografted with chromaffin cells in
      the rat striatum.
AB  - Transplantation of stem and neural progenitor cells hold great promise in the
      repair of neuronal tissue lost due to injury or disease. However, survival
      following transplantation to the adult CNS has been poor, likely due to a lack of
      neurotrophic factors, such as basic fibroblast growth factor (FGF-2), that are
      used to maintain and expand these cells in culture. Chromaffin cells produce
      several neurotrophic agents, including FGF-2, which may aid in both
      neuroprotection following injury and progenitor cell proliferation and survival.
      In addition, increased CNS catecholamines have been shown to improve functional
      recovery following insult. Thus, cotransplants of neural progenitor cells and
      chromaffin cells may be a useful clinical strategy. To address this, the survival
      of rat cortical progenitors transplanted to the adult rat striatum with and
      without bovine chromaffin cell cografts was assessed. Progenitors obtained from
      E14 embryos were prelabeled with bromodeoxyuridine (BrdU) before transplantation
      to enable later identification. Transplants were made both unilaterally and
      bilaterally, where animals received a monograft (progenitor cells alone) on one
      side and a cograft (progenitors + chromaffin cells) on the other. Histological
      results after 7, 17, and 30 days posttransplant revealed greatly improved
      survival of BrdU-labeled cells in the cografts and also less infiltration of
      presumptive immune cells. In addition, perivascular cuffing was seen in the
      monografts. In vitro progenitor cohorts stained positive for nestin, GFAP, and
      beta-tubulin III, but in vivo very few cells were found that were double labeled
      with BrdU and one of these markers. Thus, in contrast to in vitro findings,
      chromaffin cells did not enhance differentiation of progenitors in vivo during
      the 30 days posttransplantation. The results of these studies suggest that
      chromaffin cells may provide neurotrophic support to enhance survival, but not
      differentiation, of cortical progenitor grafts in the adult CNS.

PMID- 14697325
TI  - Effects of unilateral and bilateral labyrinthectomy on rat postural muscle
      properties: the soleus.
AB  - The aim of our study was to determine whether the suppression of the vestibular
      inputs could have effects on the soleus muscle properties similar to the
      modifications observed after an episode of microgravity. The inner ear lesion was
      performed by surgical labyrinthectomy. Twenty-nine male Wistar rats were used for
      this study and were divided into three experimental groups: control (CONT, n=7),
      unilateral labyrinthectomized (UL, n=14) and bilateral labyrinthectomized (BL,
      n=8). Mechanical, histochemical and electrophoretic parameters were determined 17
      days after the operation. Furthermore, electromyographic (EMG) activity of the
      soleus muscle was examined at 1 h, 1 day and 17 days. Our results showed that UL
      and BL groups did not present any sign of muscle atrophy when compared to CONT
      group. However, the contractile and phenotypical characteristics of UL and BL
      soleus muscles revealed that the muscle evolved from slow toward a slower type.
      This transition was correlated with a more tonic EMG activity pattern. To
      conclude, our data demonstrated that soleus muscle transformations observed after
      microgravity (muscle atrophy, slow-to-fast transition, phasic EMG activity) were
      not directly the consequence of a vestibular silence.

PMID- 14697326
TI  - Comparison of Tenecteplase with Alteplase on clinical rating scores following
      small clot embolic strokes in rabbits.
AB  - Tenecteplase (TNK) was engineered to have increased fibrin specificity and an
      increased half-life compared to Alteplase. Although Tenecteplase is currently
      being tested in a Phase II clinical trial in acute ischemic stroke patients,
      little is known about the pharmacology and dose-response or therapeutic window
      for Tenecteplase in embolic stroke models. In the present study, we compared
      Tenecteplase with Alteplase on behavioral outcome in rabbits with embolic
      strokes. Male New Zealand white rabbits were embolized by injecting a suspension
      of small blood clots into the middle cerebral artery (MCA) via a catheter. The
      rabbit small clot embolic stroke model (RSCEM) was used for a dose-response
      profile analysis of Tenecteplase (0.1 mg/kg-3.3 mg/kg) and Alteplase (0.9 mg/kg
      3.3 mg/kg) given intravenously 1 h following embolization. In additional studies,
      Tenecteplase (0.9 mg/kg) or Alteplase (3.3 mg/kg) was administered 3 (or 6) h
      following embolization to determine the therapeutic window for the thrombolytics.
      For both studies, behavioral analysis was conducted 24 h following embolization,
      allowing for the determination of the effective stroke dose (P50) or clot amount
      (mg) that produces neurological deficits in 50% of the rabbits. Using the RSCEM,
      a drug is considered beneficial if it significantly increases the P50 compared
      with the control group. The P50 of controls 24 h after embolization was 1.13 +/-
      0.15 mg. Rabbits treated 1 h post-embolization with Tenecteplase (0.1, 0.25, 0.9,
      1.5 or 3.3 mg/kg) had P50 values of 1.48 +/- 0.33, 2.20 +/- 0.44, 2.76 +/- 0.37,
      2.15 +/- 0.29 and 2.78 +/- 0.31 mg, respectively. In Alteplase-treated rabbits,
      only the 3.3 mg/kg dose significantly increased the group P50 by 189% compared to
      control. Tenecteplase was also effective at increasing the P50 value to 2.21 +/-
      0.43 mg if there was a 3-h delay following embolization, but not if there was a 6
      h delay before administration. Alteplase was only effective if administered 1 h
      following embolization where it significantly increased the P50 value to 3.27 +/-
      0.40 mg. This study indicates that Tenecteplase has a wide therapeutic range, a
      therapeutic window of at least 3 h and a durable effect. Moreover, the safety
      profile for Tenecteplase is similar to that of Alteplase. Tenecteplase does not
      increase the rate of intracerebral hemorrhage (ICH) above that produced by
      Alteplase. However, the therapeutic range and window for Alteplase is more
      limited than that for Tenecteplase. Our preclinical studies suggest that
      Tenecteplase has a better pharmacological profile than Alteplase and supports
      further investigation of Tenecteplase in randomized double-blinded clinical
      trials in stroke patients.

PMID- 14697327
TI  - Cyclooxygenase inhibition in nerve-injury- and TNF-induced hyperalgesia in the
      rat.
AB  - After nerve injury, cyclooxygenase-2 (COX-2) is upregulated in spinal cord and
      peripheral nerve, the latter being dependent on tumor necrosis factor-alpha
      (TNF). Here we asked whether COX inhibitors attenuate pain behavior induced by
      chronic constrictive sciatic nerve injury (CCI) or intraneural injection of TNF
      (2.5 pg/ml). Rats received either 0.9% saline, the nonselective COX inhibitor
      ibuprofen (40 mg/kg) or the selective COX-2 inhibitor celecoxib (10 or 30 mg/kg)
      twice daily by gavage started 2 days before, 12 h or 7 days after surgery.
      Mechanical allodynia and thermal hyperalgesia induced by CCI was moderately, but
      consistently attenuated by early (day -2 or 12 h after CCI), but not late (7 days
      after CCI) ibuprofen and celecoxib treatment. Mechanical allodynia, but not
      thermal hyperalgesia induced by intraneural TNF, was reduced by ibuprofen, but
      not by celecoxib treatment 5 and 7 days after injection. Sciatic nerves, lumbar
      dorsal root ganglia (DRG) and spinal cords from rats with treatment started 12 h
      after surgery were analyzed for prostaglandin E2 (PGE2) levels 10 days after CCI.
      In injured nerves and ipsilateral DRG, PGE2 levels were increased. Ibuprofen
      treatment reversed PGE2 levels in injured nerves and DRG, whereas celecoxib
      blocked increased PGE2 levels only in nerves. In spinal cord, no change in PGE2
      levels was observed. In contrast to the marked inhibition of nerve-injury-induced
      upregulation of PGE2 by COX inhibitors, the effect on pain behavior was modest.
      Nerve-injury- and TNF-induced pain-related behavior seem to be only partly
      dependent on peripheral prostaglandins.

PMID- 14697328
TI  - Early ionic and membrane potential changes caused by the pesticide rotenone in
      striatal cholinergic interneurons.
AB  - Mitochondrial metabolism impairment has been implicated in the pathogenesis of
      several neurodegenerative disorders. In the present work, we combined
      electrophysiological recordings and microfluorometric measurements from
      cholinergic interneurons obtained from a rat neostriatal slice preparation. Acute
      application of the mitochondrial complex I inhibitor rotenone produced an early
      membrane hyperpolarization coupled to a fall in input resistance, followed by a
      late depolarizing response. Current-voltage relationship showed a reversal
      potential of -80 +/- 3 mV, suggesting the involvement of a potassium (K+)
      current. Simultaneous measurement of intracellular sodium [Na+]i or calcium
      [Ca2+]i concentrations revealed a striking correlation between [Na+]i elevation
      and the early membrane hyperpolarization, whereas a significant [Ca2+]i rise
      matched the depolarizing phase. Interestingly, ion and membrane potential changes
      were mimicked by ouabain, inhibitor of the Na+-K+ATPase, and were insensitive to
      tetrodotoxin (TTX) or to a combination of glutamate receptor antagonists. The
      rotenone effects were partially reduced by blockers of ATP-sensitive K+ channels,
      glibenclamide and tolbutamide, and largely attenuated by a low Na+-containing
      solution. Morphological analysis of the rotenone effects on striatal slices
      showed a significant decrease in the number of choline acetyltransferase (ChAT)
      immunoreactive cells. These results suggest that rotenone rapidly disrupts the
      ATP content, leading to a decreased Na+-K+ATPase function and, therefore, to
      [Na+]i overload. In turn, the hyperpolarizing response might be generated both by
      the opening of ATP-sensitive K+ channels and by Na+-activated K+ conductances.
      The increase in [Ca2+]i occurs lately and does not seem to influence the early
      events.

PMID- 14697329
TI  - Axotomy abolishes NeuN expression in facial but not rubrospinal neurons.
AB  - The neuronal nuclei (NeuN) antibody, which binds to a poorly characterized
      antigen/antigens, is increasingly being used in several areas of study as a
      specific marker to identify neuronal populations. Despite the increasing reliance
      on NeuN as a panneuronal marker, changes of NeuN expression following axonal
      injury have not yet been examined. In the present study, NeuN immunoreactivity
      was analyzed in adult rodent facial motoneurons [peripheral nervous system (PNS)
      model] following nerve resection or crush and in rubrospinal neurons [central
      nervous system (CNS) model] after lesion of the dorsal lateral funiculus at the
      cervical level of the spinal cord. Peripheral nerve resection in the rat and
      mouse resulted in an almost complete loss of NeuN immunoreactivity in facial
      motoneurons by 3 days postinjury and remained absent at 28 days post-resection
      despite the survival of the neurons as evidenced by neuronal tracing. These
      results were confirmed with Western blot. In the peripheral nerve crush model of
      injury, there was an initial decline in NeuN immunoreactivity in facial
      motoneurons, but unlike the resection model, NeuN immunoreactivity began to
      return within 7 days postinjury and returned to the uninjured level of expression
      by 28 days. In contrast, axotomy in the CNS model resulted in little decline in
      NeuN immunoreactivity in the rubrospinal neurons, even after 28 days postaxotomy.
      These results indicate that NeuN expression in response to axonal injury is
      different in separate neuronal populations (PNS and CNS), and that care must be
      taken when addressing cell survival based on NeuN staining alone.

PMID- 14697330
TI  - Expression of brain natriuretic peptide by human bone marrow stromal cells.
AB  - Bone marrow stromal cells (BMSC) have been shown to generate neural cells under
      experimental conditions in vitro and following transplantation into animal models
      of stroke and traumatic CNS injury. Hastened recovery from the neurological
      deficit has not correlated with structural repair of the lesion in the stroke
      model. Secretory functions of BMSC, such as the elaboration of growth factors and
      cytokines, have been hypothesized to play a role in the enhanced recovery of
      neurological function. Using gene expression arrays, real time RT-PCR and
      radioimmunoassay, we have found that brain natriuretic peptide (BNP) is
      synthesized and released by BMSC at physiologically relevant levels in vitro.
      BNP, like its close homolog atrial natriuretic peptide (ANP), exerts powerful
      natriuretic, diuretic and vasodilatory effects. We speculate that transplanted
      BMSCs facilitate recovery from brain and spinal cord lesions by releasing BNP and
      other vasoactive factors that reduce edema, decrease intracranial pressure and
      improve cerebral perfusion.

PMID- 14697331
TI  - Protective effect of the alpha2-adrenoceptor antagonist, dexefaroxan, against
      spatial memory deficit induced by cortical devascularization in the adult rat.
AB  - The alpha2-adrenoceptor antagonist, dexefaroxan, has been shown in the rat to
      have neuroprotective and plastic effects against degenerative structural changes
      in elements of the basalocortical cholinergic system that result from cortical
      devascularization [Neuroscience 115 (2002) 41]. The present study, using the same
      experimental protocol, examined the functional consequences of cortical
      devascularization and dexefaroxan treatment in the Morris water maze memory test.
      Rats were first trained to find the hidden platform in the test, and then
      subjected to the devascularization procedure. Thirty-one days later, lesioned
      rats exhibited a significant deficit in recalling the platform location, compared
      with sham control animals. A 28-day subcutaneous infusion with dexefaroxan (0.63,
      2.5, and 10 mg rat(-1) day(-1)), starting from the moment of the
      devascularization, protected against this spatial memory deficit.

PMID- 14697332
TI  - Enhanced adhesion of monocytes via reverse signaling triggered by decoy receptor
      3.
AB  - Decoy receptor 3 (DcR3), a newly identified soluble protein belonging to the
      tumor necrosis factor receptor (TNFR) superfamily, is a receptor for Fas ligand
      (FasL), LIGHT and TL1A. It has been demonstrated that DcR3 is frequently
      overexpressed by malignant tumors arising from lung, gastrointestinal tract,
      neuronal glia and virus-associated leukemia. Recently, we demonstrated that DcR3
      is able to modulate the differentiation and activation of dendritic cells (DCs),
      and that DcR3-treated DCs skew naive T cell differentiation towards a Th2
      phenotype. In this study, we further demonstrate that DcR3 is able to induce
      actin reorganization and enhance the adhesion of monocytes and THP-1 cells by
      activating multiple signaling molecules, such as protein kinase C (PKC),
      phosphatidylinositol 3-kinase (PI3K), focal adhesion kinase (FAK) and Src
      kinases. This provides the first evidence that the soluble DcR3, like other
      immobilized members of TNFR superfamily, is able to trigger 'reverse signaling'
      to modulate cell function.

PMID- 14697333
TI  - Phenobarbital responsiveness as a uniquely sensitive indicator of hepatocyte
      differentiation status: requirement of dexamethasone and extracellular matrix in
      establishing the functional integrity of cultured primary rat hepatocytes.
AB  - We used a serum-free, highly defined primary hepatocyte culture model to
      investigate the mechanisms whereby dexamethasone (Dex) and extracellular matrix
      (ECM) coordinate cell differentiation and transcriptional responsiveness to the
      inducer, phenobarbital (PB). Low nanomolar levels of Dex and dilute
      concentrations of ECM overlay were essential in the maintenance of normal
      hepatocyte physiology, as assessed by cell morphology, LDH release, expression of
      the hepatic nuclear factors C/EBPalpha, -beta, -gamma, HNF-1alpha, -1beta, 
      4alpha, and RXRalpha, expression of prototypical hepatic marker genes, including
      albumin and transferrin, and ultimately, cellular capacity to respond to PB. The
      loss of hepatocyte integrity produced by deficiency of these components
      correlated with the activation of several stress signaling pathways including the
      MAPK, SAPK/JNK, and c-Jun signaling pathways, with resulting nuclear recruitment
      of the activated protein-1 (AP-1) complex. In Dex-deficient cultures, normal
      cellular function, including the PB induction response, was largely restored in a
      dose-dependent manner by reintroduction of nanomolar additions of the hormone, in
      the presence of ECM. Our results demonstrate critical and cooperative roles for
      Dex and ECM in establishing hepatocyte integrity and in the coordination of an
      array of liver-specific functions. These studies further establish the PB gene
      induction response as an exceptionally sensitive indicator of hepatocyte
      differentiation status.

PMID- 14697334
TI  - Stretch activation of GTP-binding proteins in C2C12 myoblasts.
AB  - Mechanical stimulation has been proposed as a fundamental determinant of muscle
      physiology. The mechanotransduction of strain and strain rate in C2C12 myoblasts
      were investigated utilizing a radiolabeled GTP analogue to detect stretch-induced
      GTP-binding protein activation. Cyclic uniaxial strains of 10% and 20% at a
      strain rate of 20% s(-1) rapidly (within 1 min) activated a 25-kDa GTPase (183 +/
      17% and 186 +/- 19%, respectively), while 2% strain failed to elicit a response
      (109 +/- 11%) relative to controls. One, five, and sixty cycles of 10% strain
      elicited 187 +/- 20%, 183 +/- 17%, and 276 +/- 38% increases in activation. A
      single 10% stretch at 20% s(-1), but not 0.3% s(-1), resulted in activation.
      Insulin activated the same 25-kDa band in a dose-dependent manner. Western blot
      analysis revealed a panel of GTP-binding proteins in C2C12 myoblasts, and
      tentatively identified the 25-kDa GTPase as rab5. In separate experiments, a 40
      kDa protein tentatively identified as Galpha(i) was activated (240 +/- 16%) by
      10% strain at 1 Hz for 15 min. These results demonstrate the rapid activation of
      GTP-binding proteins by mechanical strain in myoblasts in both a strain magnitude
      and strain rate-dependent manner.

PMID- 14697335
TI  - HGF and ligation of alphavbeta5 integrin induce a novel, cancer cell-specific
      gene expression required for cell scattering.
AB  - Hepatocyte growth factor (HGF), a cytokine involved in tumorigenesis and most
      metastases, initiates cell migration by binding to the protooncogene c-Met
      receptor. In epithelial carcinoma cells, c-Met activation causes the breakdown of
      E-cadherin cell-cell contacts leading to cell spreading. While the breakdown of E
      cadherin contacts is immediate, HGF-induced migration requires transcription. To
      test the hypothesis that this de novo mRNA synthesis includes cancer cell
      specific transcripts, we performed subtraction hybridization to isolate HGF
      induced transcripts from an endometrial epithelial carcinoma cell line, RL95-2
      (RL95), known to migrate but not to proliferate with HGF treatment. One novel
      cDNA we call Mig-7 is induced by HGF in endometrial epithelial carcinoma cell
      lines RL95 and HEC-1A before migration ensues. Ovarian, oral squamous cell, and
      colon metastatic tumors but not normal tissues express Mig-7. HGF did not induce
      Mig-7 in normal primary endometrial epithelial cells. In addition, blocking
      antibodies to alphavbeta5 integrin inhibited HGF induction of Mig-7 in RL95
      cells. Most importantly, Mig-7-specific antisense oligonucleotides inhibited
      scattering of RL95 cells in vitro. These results are the first to demonstrate
      that Mig-7 expression may be used as a cancer cell-specific target to inhibit
      cell scattering.

PMID- 14697336
TI  - Differentiation of skeletal muscle from pituitary folliculo-stellate cells and
      endocrine progenitor cells.
AB  - We previously reported the ectopic differentiation of skeletal muscle cells in a
      pituitary gland transplanted beneath a kidney capsule. Morphological observation
      suggested that the skeletal muscle cells may have differentiated from folliculo
      stellate (FS) cells in the anterior pituitary gland. However, at that time, we
      did not confirm this directly with an in vitro system. To obtain direct evidence,
      we used the Tpit/F1 cell line. The Tpit/F1 cell line was recently established
      from the pituitary gland of a temperature-sensitive T antigen transgenic mouse
      and has the characters of pituitary FS cells. Using Tpit/F1 cells, we have found
      that FS cells of the pituitary are able to differentiate into muscle cells in
      vitro. Additionally, we showed that the cells have some characteristics of
      pituitary FS cells and also express pituitary endocrine cell-specific
      transcription factor (pit-1) and prolactin genes, and can differentiate into
      striated muscle cells. The anterior pituitary gland is known to be of ectodermal
      origin, so the differentiation of its cells into striated muscle is completely
      unexpected. This is the first report of direct evidence of ectopic
      differentiation of skeletal muscle cells from pituitary cells.

PMID- 14697337
TI  - EphA3 is induced by CD28 and IGF-1 and regulates cell adhesion.
AB  - Stimulation of CD28 alone has been shown to regulate cytokine gene transcription
      and expression of the type 1 insulin-like growth factor receptor (IGF-1R) in
      lymphocytes. In this study, the ephrin receptor tyrosine kinase ephA3, was
      identified as a new CD28-responsive gene in Jurkat cells by using a human
      cytokine/receptor array. EphA3 was not detected in normal peripheral T cells, in
      any subset of thymus-derived developing T cells, or in Hodgkin's lymphoma.
      However, contrary to previous findings, EphA3 was detected in a panel of T-cell
      lymphomas. Stimulation of Jurkat cells with ephrin-A5 resulted in loss of cell
      adhesion to fibronectin and recruitment of the adapter protein CrkII to EphA3.
      Interestingly, EphA3 expression in CD28-stimulated Jurkat cells was enhanced by
      IGF-1 or by overexpression of the IGF-1R, and was suppressed by anti-IGF-1R
      blocking antibodies. The data suggest that CD28- and IGF-1-regulated expression
      of EphA3 is associated with adherence and that it may be involved in the motility
      of malignant T cells.

PMID- 14697339
TI  - Ultrastructural characterisation of a nuclear domain highly enriched in survival
      of motor neuron (SMN) protein.
AB  - Mutations in the survival of motor neuron (SMN) gene are the major cause of
      spinal muscular atrophy (SMA). The SMN gene encodes a 38-kDa protein that
      localises in the cytoplasm and in nuclear bodies termed Gemini of coiled bodies
      (gems). When visualised by immunofluorescence microscopy, gems often appeared
      either in close proximity to, or entirely overlapping with coiled (Cajal) bodies
      (CBs) implying a possible functional relationship between these nuclear domains.
      With the aim of identifying subnuclear compartments corresponding to gems, we
      have investigated the intranuclear localisation of SMN and of its interacting
      protein Gemin2 by immunoelectron microscopy in cultured cells and in liver cells
      of hibernating dormouse. These antigens are highly enriched in round-shaped
      electron-dense fibro-granular clusters (EFGCs), which also display a biochemical
      composition similar to gems visualised by immunofluorescence microscopy. Our data
      reveal a novel SMN/Gemin2 containing nuclear domain and support the idea that it
      represents the structural counterpart of gems seen in the light microscope.

PMID- 14697338
TI  - Multiple independent kinase cascades are targeted by hyperosmotic stress but only
      one activates stress kinase p38.
AB  - In this report, we analyse the effects of osmotic shock on signal transduction in
      CHO cells. We demonstrate that at least three different kinase cascades are
      switched on upon osmotic shock, namely PKA, AMPK, and MLTK. Whereas PKA from
      cells treated with forskolin activated stress kinase p38, PKA from cells treated
      with sorbitol did not activate p38, although the enzyme is activated in both
      cases as analysed in vitro using a specific peptide target. Further, osmolar
      shock activated AMPK but treatment of the cells with the AMPK activator 5-amino-4
      imidazolecarboxamide (AICAr) did not result in p38 activation, strongly
      suggesting that AMPK is not involved in stress kinase activation. Transfection of
      CHO cells with dominant negative recombinants of MLTKalpha resulted in inhibition
      of sorbitol-mediated p38 activation, indicating that the mixed-lineage kinase is
      involved in the activation of p38 by sorbitol. Finally, in CHO cells
      overexpressing wild-type MLTKalpha, no activation of AMPK of PKA could be
      demonstrated, indicating that the activated kinase cascades are not involved in a
      cross-talk process.

PMID- 14697340
TI  - Effects of Kaposi's sarcoma-associated herpesvirus ORF K1 on differentiating
      endothelium in murine embryoid bodies and teratomas.
AB  - Infection with Kaposi's sarcoma-associated herpesvirus (KSHV) is a prerequisite
      for Kaposi's sarcoma, a multicentric endothelial tumor of mixed blood vessel
      lymphatic phenotype with a marked production of endothelial basement membrane
      proteins. The viral K1 gene encodes a unique transmembrane protein capable of
      transforming T lymphocytes experimentally. We studied the effects of K1 regulated
      by the endothelium-specific tie-1 promoter in the embryonic stem cell (ES)
      derived endothelium of subcutaneous murine teratomas and in embryoid body
      cultures with and without supplemental basic fibroblast growth factor and
      vascular endothelial growth factor. K1 embryoid bodies showed no difference in
      endothelial BM protein expression, formation of basal lamina by electron
      microscopy or fractional area of endothelial growth in comparison with vector
      controls, but maturation into branching pseudovascular tubes was mildly impaired.
      Moreover, the marked increase in endothelial fraction induced by both growth
      factors in the early growth period was absent in K1 clones. Teratoma endothelium,
      which is partly derived from ES, showed increased proliferation and apoptosis in
      K1 tumors, coinciding with a possible increased tendency for microhemorrhages. K1
      can thus modulate endothelial cell turnover and growth factor response, but does
      not alter the extracellular matrix of differentiating endothelial cells.

PMID- 14697341
TI  - Characterization of the antigenicity of the formiminotransferase-cyclodeaminase
      in type 2 autoimmune hepatitis.
AB  - Human formiminotransferase-cyclodeaminase (hFTCD) is the autoantigen recognized
      by anti-liver cytosol type 1 (LC1) autoantibodies in type 2 autoimmune hepatitis
      (AIH) patients. In rats, this octameric protein is localized on the Golgi
      apparatus and binds brain microtubules (MTs) and vimentin. Subcellular
      localization of human formiminotransferase-cyclodeaminase and its implication in
      the pathogenesis of autoimmune hepatitis are unknown. Localization of the human
      formiminotransferase-cyclodeaminase in human hepatocytes was done using indirect
      immunofluorescence and subcellular fractionations followed by in vitro binding
      techniques. The formiminotransferase-cyclodeaminase antigen at two distinct
      locations in hepatocytes, free in the cytosol and associated with the Golgi
      membranes are recognized by anti-liver cytosol type 1 autoantibodies. The human
      formiminotransferase-cyclodeaminase binds reversibly to the Golgi membranes and
      this complex formation is increased by anti-liver cytosol type 1 autoantibodies.
      Finally, human formiminotransferase-cyclodeaminase does not interact with liver
      specific cytoskeleton proteins. Anti-liver cytosol type 1 autoantibodies are
      directed against the mature high molecular form of human formiminotransferase
      cyclodeaminase. Therefore, the subcellular location of the protein may influence
      the production of autoantibodies and their role in the pathogenesis of type 2
      autoimmune hepatitis. This antigen-driven response does not appear to be
      facilitated or enhanced by a possible interaction between human
      formiminotransferase-cyclodeaminase and hepatocyte cytoskeleton proteins.

PMID- 14697342
TI  - Induction and regulation of acute phase proteins in transdifferentiated
      hepatocytes.
AB  - Acute phase proteins (APPs) are predominantly synthesized in the liver and play
      an important role in restoring homeostasis. In the present study, we set out to
      answer two questions using transdifferentiated hepatocytes induced from
      pancreatic cells as a model for studying the acute phase response. Firstly, do
      transdifferentiated hepatocytes express acute phase proteins following culture
      with glucocorticoid and cytokines? Secondly, what is the molecular basis of the
      induction of acute phase proteins in transdifferentiated hepatocytes? Hepatic
      transdifferentiation was induced in 11.5-day mouse embryonic pancreas or the
      pancreatic cell line AR42J-B13 (B13) by culture with dexamethasone. We found that
      acute phase proteins [alpha2-macroglobulin (MG), haptoglobin (Hp)] were induced
      in both systems following culture with dexamethasone. The combined treatment of
      dexamethasone and oncostatin M (OSM) enhanced the expression of the acute phase
      proteins in B13 cells and the mechanism of the up-regulation by the cytokine is
      probably mediated by phosphorylation of STAT3 and STAT1. In addition, ectopic
      expression of either C/EBPbeta or C/EBPalpha in B13 cells induced haptoglobin
      expression and culture with oncostatin M was sufficient to enhance the expression
      of haptoglobin in C/EBPbeta transfected cells from 18% to 43%. The results of the
      present study indicate transdifferentiated hepatocytes have the potential to be a
      useful model to study liver function in vitro.

PMID- 14697343
TI  - Limited expression of nuclear pore membrane glycoprotein 210 in cell lines and
      tissues suggests cell-type specific nuclear pores in metazoans.
AB  - The nuclear pore complex (NPC) is the only known gateway for nucleocytoplasmic
      traffic. The nuclear pore membrane glycoprotein 210 (POM210/gp210) is considered
      to be important for the assembly and structure of pore complexes in metazoan
      cells. However, here we demonstrate cell-type specific expression of the gp210
      protein during mouse organogenesis. As shown previously for its mRNA, distinct
      expression of the gp210 was seen in developing epithelia and some other cell
      types, whereas it was undetectable in nuclei of several other embryonic tissue
      compartments. In sharp contrast, monoclonal antibody 414 recognizing four non
      membrane nucleoporins, stained the nuclear envelope of all cell types. In four
      cultured mouse cell lines, gp210 mRNA and protein were below detection levels, in
      contrast to some other nucleoporins tested. Distinct expression of gp210 mRNA and
      protein was seen in cultured mouse embryonic stem (ES) cells. These findings
      support the view of cell-type specific NPCs in metazoans and that the gp210 gene
      is regulated by cell-type specific control elements not shared by other
      nucleoporins. Although it cannot be excluded that very low expression levels of
      gp210 are sufficient to allow attachment of NPCs, a more likely alternative is
      that it has cell-type specific functions.

PMID- 14697344
TI  - RGD- and MLD-disintegrins, jarastatin and EC3, activate integrin-mediated
      signaling modulating the human neutrophils chemotaxis, apoptosis and IL-8 gene
      expression.
AB  - The effects of jarastatin (JT), a monomeric RGD-disintegrin, were compared with
      those of the heterodimeric MLD-disintegrin, EC3, on human neutrophil activation
      and functions. Both disintegrins inhibited neutrophil chemotaxis induced by fMet
      Leu-Phe and were also potent chemotactic agents. These effects were accompanied
      by an increase in actin polymerization, and both were inhibited by genistein, a
      tyrosine kinase inhibitor. While JT, but not other RGD-disintegrins, inhibited
      EC3-induced chemotaxis, EC3 was not able to inhibit JT effect. The chemotactic
      effect of JT was blocked by anti-alpha(M) antibody whereas anti-alpha(9)beta(1)
      inhibited EC3 effect. Both JT and EC3 induced focal adhesion kinase (FAK) and
      phosphoinositide 3-kinase (PI3K) activation. Accordingly, LY294002, a PI3K
      inhibitor, impaired their chemotactic effect on neutrophils. JT induced Erk-2
      translocation to nucleus and a delay of the spontaneous apoptosis of neutrophils
      in vitro. In contrast, EC3 inhibited Erk-2 activation and had a proapoptotic
      effect. These effects were reverted by PD98059, an MEK 1/2 inhibitor and blocked
      by z-VAD-FMK, a caspase inhibitor. In addition, JT, but not EC3, increased the IL
      8 mRNA levels in neutrophils. The data indicate that JT and EC3 directly activate
      an integrin-coupled signaling and modulate the MAPK pathway in different ways,
      leading the neutrophils to express different functional response.

PMID- 14697345
TI  - Sphingomyelin synthase as a potential target for D609-induced apoptosis in U937
      human monocytic leukemia cells.
AB  - Tricyclodecan-9-yl-xanthogenate (D609) is a selective tumor cytotoxic agent.
      However, the mechanisms of action of D609 against tumor cells have not been well
      established. Using U937 human monocytic leukemia cells, we examined the ability
      of D609 to inhibit sphingomyelin synthase (SMS), since inhibition of SMS may
      contribute to D609-induced tumor cell cytotoxicity via modulating the cellular
      levels of ceramide and diacylglycerol (DAG). The results showed that D609 is
      capable of inducing U937 cell death by apoptosis in a dose- and time-dependent
      manner. The induction of U937 cell apoptosis was associated with an inhibition of
      SMS activity and a significant increase in the intracellular level of ceramide
      and decrease in that of sphingomyelin (SM) and DAG, which resulted in an
      elevation of the ratio between ceramide and DAG favoring the induction of
      apoptosis. In addition, incubation of U937 cells with C(6)-ceramide and/or H7 (a
      selective PKC inhibitor) reduced U937 cell viability; whereas pretreatment of the
      cells with a PKC activator, PMA or 1-oleoyl-2-acetylglycerol (OAG), attenuated
      D609-induced U937 cell apoptosis. These results suggest that SMS is a potential
      target of D609 and inhibition of SMS may contribute to D609-induced tumor cell
      death via modulation of the cellular levels of ceramide and DAG.

PMID- 14697346
TI  - NIP1/XB51/NECAB3 is a potential substrate of Nek2, suggesting specific roles of
      Nek2 in Golgi.
AB  - Nek2 is a mammalian protein kinase structurally homologous to Aspergillus NIMA.
      We previously observed that the Nek2 protein was localized in multiple sites
      within a cell in a cell cycle stage-specific manner. Such dynamic behavior of
      Nek2 allowed us to propose that Nek2 may be a mitotic regulator that is involved
      in diverse cell cycle events. To better understand the cellular processes in
      which Nek2 participates, we carried out yeast two-hybrid screening and isolated
      Nek2-Interacting Protein 1 (NIP1), which has been also named as XB51 and NECAB3.
      Physical interactions of Nek2 with NIP1 were confirmed. In fact, Nek2 can
      phosphorylate NIP1 in vivo. Immunostaining experiments revealed that NIP1 is a
      Golgi protein. These results propose a possible involvement of Nek2 in biological
      processes of the Golgi body, perhaps in relation to the inheritance of Golgi
      during mitosis or to cell cycle stage-specific regulation of exocytosis.

PMID- 14697347
TI  - The opsonin MFG-E8 is a ligand for the alphavbeta5 integrin and triggers DOCK180
      dependent Rac1 activation for the phagocytosis of apoptotic cells.
AB  - Opsonization of apoptotic cells facilitates recognition by phagocytes for the
      rapid clearance of potentially inflammatory cellular material. The secreted
      glycoprotein Milk Fat Globule Factor-E8 (MFG-E8) is a member of this family of
      bridging molecules and is believed to bind phosphatidylserine (PS) on the dying
      cell, linking it to integrin receptors on the phagocyte. Here we report the
      characterization of a functional signaling module involving MFG-E8, alphavbeta5
      integrin, and DOCK180 for the activation of Rac1. We show that MFG-E8 and DOCK180
      are both expressed in phagocytic-competent primary immature dendritic cells (DCs)
      and DC2.4 cells, and are potently down-regulated upon DC maturation, consistent
      with their role in phagocytosis and antigen capture. Coexpression of MFG-E8 with
      alphavbeta5 integrin potentiated integrin-mediated Rac1 activation, which was
      abrogated by mutagenesis in the RGD motif in MFG-E8. Moreover, expression of
      antisense DOCK180 abrogated MFG-E8-alphavbeta5-mediated Rac activation and
      impaired the phagocytosis of apoptotic cells. These data demonstrate a
      biochemical link between an opsonin of apoptotic cells, the alphavbeta5 integrin,
      and the Crk-DOCK180-Rac1 pathway, and importantly, show that MFG-E8 and DOCK180
      are expressed according to the functional status of the phagocyte.

PMID- 14697349
TI  - A Notch feeling of somite segmentation and beyond.
AB  - Vertebrate segmentation is manifested during embryonic development as serially
      repeated units termed somites that give rise to vertebrae, ribs, skeletal muscle
      and dermis. Many theoretical models including the "clock and wavefront" model
      have been proposed. There is compelling genetic evidence showing that Notch-Delta
      signaling is indispensable for somitogenesis. Notch receptor and its target
      genes, Hairy/E(spl) homologues, are known to be crucial for the ticking of the
      segmentation clock. Through the work done in mouse, chick, Xenopus and zebrafish,
      an oscillator operated by cyclical transcriptional activation and delayed
      negative feedback regulation is emerging as the fundamental mechanism underlying
      the segmentation clock. Ubiquitin-dependent protein degradation and probably
      other posttranslational regulations are also required. Fgf8 and Wnt3a gradients
      are important in positioning somite boundaries and, probably, in coordinating
      tail growth and segmentation. The circadian clock is another biochemical
      oscillator, which, similar to the segmentation clock, is operated with a negative
      transcription-regulated feedback mechanism. While the circadian clock uses a more
      complicated network of pathways to achieve homeostasis, it appears that the
      segmentation clock exploits the Notch pathway to achieve both signal generation
      and synchronization. We also discuss mathematical modeling and future directions
      in the end.

PMID- 14697350
TI  - Cell migration: Rho GTPases lead the way.
AB  - Rho GTPases control signal transduction pathways that link cell surface receptors
      to a variety of intracellular responses. They are best known as regulators of the
      actin cytoskeleton, but in addition they control cell polarity, gene expression,
      microtubule dynamics and vesicular trafficking. Through these diverse functions,
      Rho GTPases influence many aspects of cell behavior. This review will focus
      specifically on their role in cell migration.

PMID- 14697351
TI  - Getting a GR(i)P on oligodendrocyte development.
AB  - One of the most extensively studied of mammalian cells is the oligodendrocyte,
      the myelin-forming cell of the central nervous system. The ancestry and
      development of this cell have been studied with every approach utilized by
      developmental biologists. Such detailed efforts have the potential of providing
      paradigms of relevance to those interested in analyzing the ancestry and
      development of any cell type. One of the striking features of studies on the
      development of oligodendrocytes is that different analytical approaches have led
      to strikingly different theoretical views regarding the ancestry of these cells.
      On one extreme is the hypothesis that the steps leading to the generation of
      oligodendrocytes begin with the generation of a glial-restricted precursor (GRP)
      cell from neuroepithelial stem cells. GRP cells are thought to be capable of
      giving rise to all glial cells (including oligodendrocytes and multiple astrocyte
      populations), but not to neurons, a process that appears to require progression
      through further stages of greater lineage restriction. On the other extreme is
      the hypothesis that oligodendrocytes are derived from a precursor cell that
      generates only motor neurons and oligodendrocytes, with astrocytes being
      generated through a separate lineage. In this review, we critically consider the
      various contributions to understanding the ancestry of oligodendrocytes, with
      particular attention to the respective merits of the GRP cell vs. the motor
      neuron-oligodendrocyte precursor (MNOP) cell hypothesis. We draw the conclusion
      that, at present, the strengths of the GRP cell hypothesis outweigh those of the
      MNOP hypothesis and other hypotheses suggesting oligodendrocytes are
      developmentally more related to motor neurons than to astrocytes. Moreover, it is
      clear from existing data that, following the period of motor neuron generation,
      the major glial precursor cell in the embryonic spinal cord is the GRP cell, and
      that multiple previous studies on the earliest stages of oligodendrocyte
      generation in the developing spinal cord have been focused on a differentiation
      stage of GRP cells.

PMID- 14697352
TI  - Integrins on eggs: the betaC subunit is essential for formation of the cortical
      actin cytoskeleton in sea urchin eggs.
AB  - Eggs of several metazoans have been demonstrated to express integrins; however,
      their function is unclear. Previous studies have shown that the betaC integrin
      subunit is expressed on unfertilized sea urchin eggs and proteolytically removed
      at fertilization. Here we report that the betaC subunit is reexpressed on the egg
      surface immediately after fertilization. Using morpholino antisense
      oligonucleotides to block translation, we show that without betaC expression,
      eggs undergo cleavage resulting in loosely adherent cells that fail to develop
      beyond a blastula. Without betaC containing integrins, the cortical actin network
      of the egg does not form, yet contractile rings appear. Coinjection of RNA
      encoding the betaC or chicken beta1 subunit, but lacking the morpholino target
      sequence, rescues the cortical actin network and normal embryos result.
      Coinjection of RNA encoding the betaC subunit lacking the cytoplasmic domain
      fails to rescue. These studies demonstrate that the cortical actin cytoskeleton
      is anchored by betaC integrins and contractile ring actin is not. We suggest that
      one important function of egg integrins is to organize the actin cortex.

PMID- 14697353
TI  - Requirement for fibroblast growth factor 10 or fibroblast growth factor receptor
      2-IIIb signaling for cecal development in mouse.
AB  - Epithelial-mesenchymal interactions are critical for the formation of
      gastrointestinal buds such as the cecum from the midgut, but the mechanisms
      regulating this process remain unclear. To investigate this problem, we have
      studied the temporal and spatial expression of key genes known to orchestrate
      branching morphogenesis. At E10.5, Fibroblast growth factor 10 (Fgf10) is
      specifically expressed in the mesenchyme above the future cecal epithelial bud,
      whereas Fgfr2b is found throughout the gut epithelium. From E11.5 onwards, Fgf10
      expression is found throughout the cecum mesenchyme. Other relevant signaling
      molecules such as Sonic hedgehog, Wnt2b, and Tbx4 transcripts are found
      throughout the gut epithelium, including the cecum. Epithelial expression is also
      seen for Sprouty2, but only from E14.5 onwards. By contrast, Bone morphogenetic 4
      (Bmp4) and Pitx2 are specifically expressed in the mesenchyme of the cecal bud at
      E11.5. Abrogation of either Fgf10 or Fgfr2b leads to similar phenotypes
      characterized by an arrest of epithelial invasion into the cecal mesenchymal
      tissue. However, a bud of undifferentiated cecal mesenchymal tissue is maintained
      throughout development. Our results further indicate that mesenchymal FGF10 acts
      mostly through the epithelial FGFR2b receptor; thereby triggering invasion of the
      midgut epithelium into the adjacent mesenchyme via an increased rate of
      epithelial proliferation at the tip of the cecum. Thus, FGF10 signaling via
      FGFR2b appears to be critical in the extension of the epithelium into the
      mesenchyme during cecal development.

PMID- 14697354
TI  - Imaging filopodia dynamics in the mouse blastocyst.
AB  - During mammalian development, the first cell lineage diversification event occurs
      in the blastocyst, when the trophectoderm (TE) and the inner cell mass (ICM)
      become established. Part of the TE (polar) remains in contact with the ICM and
      differs from the mural TE (mTE) which is separated from the ICM by a cavity known
      as the blastocoele. The presence of filopodia connecting ICM cells with the
      distant mural TE cells through the blastocoelic fluid was investigated in this
      work. We describe two types of actin-based cell projections found in freshly
      dissected and in vitro cultured expanding blastocysts: abundant short filopodia
      projecting into the blastocoelic cavity that present a continuous undulating
      behavior; and long, thin traversing filopodia connecting the mural TE with the
      ICM. Videomicroscopy analyses revealed the presence of vesicle-like structures
      moving along traversing filopodia and dynamic cytoskeletal rearrangements. These
      observations, together with immunolocalization of the FGFR2 and the ErbB3
      receptors to these cell extensions, suggest that they display signal transduction
      activity. We propose that traversing filopodia are employed by mitotic mTE cells
      to receive the required signals for cell division after they become distant to
      the ICM.

PMID- 14697355
TI  - Inhibition of mesodermal fate by Xenopus HNF3beta/FoxA2.
AB  - The winged-helix transcription factor HNF3beta/FoxA2 is expressed in embryonic
      organizing centers of the gastrulating mouse, frog, fish, and chick. In the
      mouse, HNF3beta is required for the formation of the mammalian node and
      notochord, and can induce ectopic floor plate formation when misexpressed in the
      developing neural tube; HNF3beta expression in the extraembryonic endoderm is
      also necessary for the proper morphogenesis of the mammalian primitive streak. In
      the frog Xenopus laevis, several lines of evidence suggest that the related
      winged-helix factor Pintallavis functions as the ortholog of mammalian HNF3beta
      in both axial mesoderm and neurectoderm; the role of Xenopus HNF3beta itself,
      however, has not been clearly defined, and is the subject of this study. HNF3beta
      is widely expressed in the vegetal pole but, as previously suggested, is excluded
      from the gastrula-stage mesoderm. We find that expression of an HNF3beta
      Engrailed repressor fusion protein induces ectopic axes and inhibits head
      formation in Xenopus embryos, while ectopic HNF3beta inhibits mesoderm and
      anterior endoderm formation in explant assays and in vivo. Our studies suggest
      that HNF3beta target genes function to limit the extent of mesoderm formation in
      the Xenopus gastrula, and point to related roles for Xenopus HNF3beta and the
      extraembryonic component of mammalian HNF3beta during vertebrate gastrulation.

PMID- 14697356
TI  - FLASH, a component of the FAS-CAPSASE8 apoptotic pathway, is directly regulated
      by Hoxb4 in the notochord.
AB  - The Hox genes are a family of homeodomain-containing transcription factors that
      confer positional identity during development. Although their regulation and
      function have been extensively studied, very little is known of their downstream
      target genes. Here we show that Hoxb4 directly induces the expression of FLASH in
      the notochord of embryos after neurulation. FLASH is a component of the FAS
      CAPSASE8 apoptotic pathway, and blocking its activity, or that of Hoxb4, prevents
      apoptosis in the notochord.

PMID- 14697357
TI  - The two steps of vulval induction in Oscheius tipulae CEW1 recruit common
      regulators including a MEK kinase.
AB  - The cell interactions that specify the spatial pattern of vulval precursor cell
      (VPC) fates differ between the nematodes Oscheius tipulae CEW1 and Caenorhabditis
      elegans. In the former, the centered pattern of fates is obtained by two
      successive inductions from the gonadal anchor cell, whereas in the latter, a
      single inductive step by the anchor cell (EGF-Ras-MAP kinase pathway) can act as
      a morphogen and is reinforced by lateral signaling between the vulval precursors
      (Notch pathway). We performed a genetic screen for vulva mutants in O. tipulae
      CEW1. Here we present the mutants that specifically affect the vulval induction
      mechanisms. Phenotypic and epistatic analyses of these mutants show that both
      vulval induction steps share common components, one of which appears to be MEK
      kinase(s). Moreover, the inductive pathway (including MEK kinase) influences the
      competence of the vulval precursor cells and more strikingly their division
      pattern as well, irrespective of their vulval fate. Finally, a comparison of
      vulval mutant phenotypes obtained in C. elegans and O. tipulae CEW1 highlights
      the evolution of vulval induction mechanisms between the two species.

PMID- 14697358
TI  - The minibrain kinase homolog, mbk-2, is required for spindle positioning and
      asymmetric cell division in early C. elegans embryos.
AB  - In the newly fertilized Caenorhabditis elegans zygote, cytoplasmic determinants
      become localized asymmetrically along the anterior-posterior (A-P) axis of the
      embryo. The mitotic apparatus then orients so as to cleave the embryo into
      anterior and posterior blastomeres that differ in both size and developmental
      potential. Here we describe a role for MBK-2, a member of the Dyrk family of
      protein kinases, in asymmetric cell division in C. elegans. In mbk-2 mutants, the
      initial mitotic spindle is misplaced and cytoplasmic factors, including the
      germline-specific protein PIE-1, are mislocalized. Our findings support a model
      in which MBK-2 down-regulates the katanin-related protein MEI-1 to control
      spindle positioning and acts through distinct, as yet unknown factors, to control
      the localization of cytoplasmic determinants. These findings in conjunction with
      work from Schizosaccharomyces pombe indicate a possible conserved role for Dyrk
      family kinases in the regulation of spindle placement during cell division.

PMID- 14697359
TI  - Annexin II-mediated plasmin generation activates TGF-beta3 during epithelial
      mesenchymal transformation in the developing avian heart.
AB  - Epithelial-mesenchymal transformation (EMT), the process by which epithelial
      cells are converted into motile, invasive mesenchymal cells, is critical to
      valvulogenesis. Transforming growth factor-beta3 (TGF-beta3), an established
      mediator of avian atrioventricular (AV) canal EMT, is secreted as a latent
      complex. In vitro, plasmin-mediated proteolysis has been shown to release active
      TGF-betas from the latent complex. Annexin II, a co-receptor for tissue
      plasminogen activator (tPA) and plasminogen, promotes cell-surface generation of
      the serine protease plasmin. Here, we show that annexin II-mediated plasmin
      activity regulates release of active TGF-beta3 during chick AV canal EMT. Primary
      embryonic endocardial-derived cells express annexin II which promotes plasminogen
      activation in vitro. Incubation of heart explant cultures with either
      alpha(2)antiplasmin (alpha(2)AP), a major physiological plasmin inhibitor, or
      anti-annexin II IgG, blocked EMT by approximately 80%, and 50%, respectively.
      Anti-annexin II IgG-mediated inhibition of EMT was overcome by the addition of
      recombinant TGF-beta3. Upon treatment with anti-annexin II IgG or alpha(2)AP,
      conditioned medium from heart explant cultures showed absence of the active
      fragment of TGF-beta3 by Western blot analysis and a approximately 50% decrease
      in TGF-beta specific bioactivity. Our results suggest that annexin II-mediated
      plasmin activity regulates the release of active TGF-beta during cardiac valve
      development in the avian heart.

PMID- 14697360
TI  - Xenopus tropicalis nodal-related gene 3 regulates BMP signaling: an essential
      role for the pro-region.
AB  - In vertebrates, nodal-related genes are crucial for specifying mesendodermal cell
      fates. Six nodal-related genes have been identified in Xenopus, but only one,
      nodal, has been identified in the mouse. The Xenopus nodal-related gene 3 (Xnr3),
      however, lacks the mesoderm-inducing activity of the other five nodal-related
      genes in Xenopus, and can directly induce neural tissue in animal caps by
      antagonizing BMP signals. In this study, we isolated three clones of the Xenopus
      (Silurana) tropicalis nodal-related gene 3 (Xtnr3) and analyzed their function.
      The Xtnr3 genes show high homology to Xnr3 and have the same activity. Southern
      blot and genomic PCR analyses indicate that the X. tropicalis genome has
      duplications in the Xtnr3 gene sequences and our three clones represent separate
      gene loci. We also found a partial clone of Xtnr3 that coded for the N-terminal
      part of its pro-region. Surprisingly, this sequence also induced neural tissue by
      antagonizing BMP signals, and its coded protein physically associated with BMP4
      mature protein. Furthermore, we showed that the pro-region of Xnr5 has the same
      activity. Together, these findings indicate that the pro-region of nodal-related
      genes acts antagonistically towards BMP signals, which identifies a novel
      mechanism for the inhibition of BMP signaling.

PMID- 14697361
TI  - Neurotrophin-independent attraction of growing sensory and motor axons towards
      developing Xenopus limb buds in vitro.
AB  - The mechanisms for directing axons to their targets in developing limbs remain
      largely unknown though recent studies in mice have demonstrated the importance of
      neurotrophins in this process. We now report that in co-cultures of larval
      Xenopus laevis limb buds with spinal cords and dorsal root ganglia of Xenopus and
      axolotl (Ambystoma mexicanum) axons grow directly to the limb buds over distances
      of up to 800 microm and in particular to sheets of epidermal cells which migrate
      away from the limb buds and also tail segments in culture. This directed axonal
      growth persists in the presence of trk-IgG chimeras, which sequester
      neurotrophins, and k252a, which blocks their actions mediated via trk receptors.
      These findings indicate that developing limb buds in Xenopus release diffusible
      factors other than neurotrophins, able to attract growth of sensory and motor
      axons over long distances.

PMID- 14697363
TI  - Expression of the soluble adenylyl cyclase during rat spermatogenesis: evidence
      for cytoplasmic sites of cAMP production in germ cells.
AB  - To gain insight into the mechanisms of cAMP signaling in germ cells, the
      expression and subcellular localization of the full-length form of the soluble
      adenylyl cyclase (sAC) was investigated during rat spermatogenesis and in
      spermatozoa. A full-length sAC-specific antibody was generated by using a
      glutathione S-transferase (GST)-sAC carboxyl-terminal region (1399aa-1608aa)
      fusion protein as the antigen. The selectivity of the purified antibody was
      confirmed by immunoblotting with lysates from HEK293 cells overexpressing full
      length sAC or truncated sAC. Western blot analysis demonstrated that full-length
      sAC protein appeared on day 25 during testis development. The expression levels
      increased progressively on days 30 and 35 and remained elevated in adult testis.
      Full-length sAC protein is retained in spermatozoa from the cauda epididymis.
      Consistent with the timing of the appearance of the Western blot signal,
      immunohistochemistry with testis sections at different stages of development
      detected sAC in late pachytene spermatocytes as well as round and elongating
      spermatids. Further experiments on the subcellular localization of native or
      recombinant enzymes revealed that full-length sAC is not only recovered in
      soluble fractions but also in particulate fractions of testis extracts.
      Immunofluorescence detection showed localization of the protein in the cytoplasm
      as well as in organelles of pachytene spermatocytes and spermatids. These
      findings indicate that cAMP production in spermatids and spermatozoa may occur at
      sites other than the plasma membrane and suggest that full-length sAC may play a
      role during spermatid differentiation.

PMID- 14697362
TI  - HB-EGF directs stromal cell polyploidy and decidualization via cyclin D3 during
      implantation.
AB  - Stromal cell polyploidy is a unique phenomenon that occurs during uterine
      decidualization following embryo implantation, although the developmental
      mechanism still remains elusive. The general consensus is that the aberrant
      expression and altered functional activity of cell cycle regulatory molecules at
      two particular checkpoints G1 to S and G2 to M in the cell cycle play an
      important role in the development of cellular polyploidy. Despite the compelling
      evidence of intrinsic cell cycle alteration, it has been implicated that the
      development of cellular polyploidy may be controlled by specific actions of
      extracellular growth regulators. Here we show a novel role for heparin-binding
      EGF-like growth factor (HB-EGF) in the developmental process of stromal cell
      polyploidy in mice. HB-EGF, which is one of the earliest known molecular
      mediators of implantation in mice and humans, promotes stromal cell polyploidy
      via upregulation of cyclin D3. Adenoviral delivery of antisense cyclin D3
      attenuates cyclin D3 expression and abrogates HB-EGF-induced stromal cell
      polyploidy in vitro and in vivo. Collectively, the results demonstrate that the
      regulation of stromal cell polyploidy and decidualization induced by HB-EGF
      depend on cyclin D3 induction.

PMID- 14697364
TI  - Snail family members and cell survival in physiological and pathological cleft
      palates.
AB  - Palate fusion is a complex process that involves the coordination of a series of
      cellular changes including cell death and epithelial to mesenchymal transition
      (EMT). Since members of the Snail family of zinc-finger regulators are involved
      in both triggering of the EMT and cell survival, we decided to study their
      putative role in palatal fusion. Furthermore, Snail genes are induced by
      transforming growth factor beta gene (TGF-beta) superfamily members, and TGF
      beta(3) null mutant mice (TGF-beta(3)-/-) show a cleft palate phenotype. Here we
      show that in the wild-type mouse at the time of fusion, Snail is expressed in a
      few cells of the midline epithelial seam (MES), compatible with a role in
      triggering of the EMT in a small subpopulation of the MES. We also find an
      intriguing relationship between the expression of Snail family members and cell
      survival associated to the cleft palate condition. Indeed, Snail is expressed in
      the medial edge epithelial (MEE) cells in TGF-beta(3)-/-mouse embryo palates,
      where it is activated by the aberrant expression of its inducer, TGF-beta(1), in
      the underlying mesenchyme. In contrast to Snail-deficient wild-type pre-adhesion
      MEE cells, Snail-expressing TGF-beta(3) mutant MEE cells survive as they do their
      counterparts in the chick embryo. Interestingly, Slug is the Snail family member
      expressed in the chick MEE, providing another example of interchange of Snail and
      Slug expression between avian and mammalian embryos. We propose that in the
      absence of TGF-beta(3), TGF-beta(1) is upregulated in the mesenchyme, and that in
      both physiological (avian) and pathological (TGF-beta(3)-/-mammalian) cleft
      palates, it induces the expression of Snail genes promoting the survival of the
      MEE cells and permitting their subsequent differentiation into keratinized
      stratified epithelium.

PMID- 14697365
TI  - Dlx genes integrate positive and negative signals during feather bud development.
AB  - In the embryonic chicken skin, feather buds and the intervening interbud tissue
      form in a reiterated and sequential pattern that is dependent on interactions
      between the epidermis and dermis. Feather promoting and inhibiting signals such
      as fibroblast growth factors (FGF) and bone morphogenetic proteins (BMP),
      respectively, direct the formation of this periodic pattern. However, the
      transcription factors that mediate the response to these signals and transmit
      this information to downstream effector genes are largely unknown. Here we have
      explored the DLX transcription factors as candidate transcriptional mediators
      downstream of the described feather patterning signals. We show that several Dlx
      members are expressed in the dermis and epidermis of the developing feather buds
      and their expression is induced in embryonic chick skin by the ectopic activation
      of BMP and FGF signaling. Misexpression of Dlx in the chick skin leads to both
      feather loss and feather bud fusions, suggesting that DLX proteins play a
      negative as well as a positive role in feather development. Moreover, DLX
      regulates the expression of NCAM and tenascin, molecules that are important for
      feather bud initiation as well as bud outgrowth and morphogenesis. Our results
      suggest that DLX transcription factors serve to integrate and transduce feather
      patterning signals to downstream effector molecules.

PMID- 14697366
TI  - Regulation of neuroD2 expression in mouse brain.
AB  - The basic helix-loop-helix (bHLH) transcription factor, neuroD2, induces neuronal
      differentiation and promotes neuronal survival. Reduced levels of neuroD2 were
      previously shown to cause motor deficits, ataxia, and seizure propensity. Because
      neuroD2 levels may be critical for brain function, we studied the regulation of
      neuroD2 gene in cell culture and transgenic mouse models. In transgenic mice, a
      10-kb fragment of the neuroD2 promoter fully recapitulated the endogenous neuroD2
      staining pattern. A 1-kb fragment of the neuroD2 promoter drove reporter gene
      expression in most, but not all neuroD2-positive neuronal populations. Mutation
      of two critical E-boxes, E4 and E5 (E4 and E5 situated 149 and 305 bp upstream of
      the transcriptional start site) eliminated gene expression. NeuroD2 expression
      was diminished in mice lacking neurogenin1 demonstrating that neurogenin1
      regulates neuroD2 during murine brain development. These studies demonstrate that
      neuroD2 expression is highly dependent on bHLH-responsive E-boxes in the proximal
      promoter region, that additional distal regulatory elements are important for
      neuroD2 expression in a subset of cortical neurons, and that neurogenin1
      regulates neuroD2 expression during mouse brain development.

PMID- 14697367
TI  - Transcription factor Ap-2alpha is necessary for development of embryonic
      melanophores, autonomic neurons and pharyngeal skeleton in zebrafish.
AB  - The genes that control development of embryonic melanocytes are poorly defined.
      Although transcription factor Ap-2alpha is expressed in neural crest (NC) cells,
      its role in development of embryonic melanocytes and other neural crest
      derivatives is unclear because mouse Ap-2alpha mutants die before melanogenesis.
      We show that zebrafish embryos injected with morpholino antisense
      oligonucleotides complementary to ap-2alpha (ap-2alpha MO) complete early
      morphogenesis normally and have neural crest cells. Expression of c-kit, which
      encodes the receptor for the Steel ligand, is reduced in these embryos, and,
      similar to zebrafish c-kit mutant embryos, embryonic melanophores are reduced in
      number and migration. The effects of ap-2alpha MO injected into heterozygous and
      homozygous c-kit mutants support the notion that Ap-2alpha works through C-kit
      and additional target genes to mediate melanophore cell number and migration. In
      contrast to c-kit mutant embryos, in ap-2alpha MO-injected embryos, melanophores
      are small and under-pigmented, and unexpectedly, analysis of mosaic embryos
      suggests Ap-2alpha regulates melanophore differentiation through cell non
      autonomous targets. In addition to melanophore phenotypes, we document reduction
      of other neural crest derivatives in ap-2alpha MO-injected embryos, including jaw
      cartilage, enteric neurons, and sympathetic neurons. These results reveal that Ap
      2alpha regulates multiple steps of melanophore development, and is required for
      development of other neuronal and non-neuronal neural crest derivatives.

PMID- 14697368
TI  - Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies
      cardiac SP cells in the developing and adult heart.
AB  - Stem cells are important in the maintenance and repair of adult tissues. A
      population of cells, termed side population (SP) cells, has stem cell
      characteristics as they have been shown to contribute to diverse lineages. In
      this study, we confirm that Abcg2 is a determinant of the SP cell phenotype.
      Therefore, we examined Abcg2 expression during murine embryogenesis and observed
      robust expression in the blood islands of the E8.5 yolk sac and in developing
      tissues including the heart. During the latter stages of embryogenesis, Abcg2
      identifies a rare cell population in the developing organs. We further establish
      that the adult heart contains an Abcg2 expressing SP cell population and these
      progenitor cells are capable of proliferation and differentiation. We define the
      molecular signature of cardiac SP cells and compare it to embryonic stem cells
      and adult cardiomyocytes using emerging technologies. We propose that the cardiac
      SP cell population functions as a progenitor cell population for the development,
      maintenance, and repair of the heart.

PMID- 14697369
TI  - Hedgehog signaling is required for the differentiation of ES cells into
      neurectoderm.
AB  - Mouse embryonic stem cells can differentiate in vitro into cells of the nervous
      system, neurons and glia. This differentiation mimics stages observed in vivo,
      including the generation of primitive ectoderm and neurectoderm in embryoid body
      culture. We demonstrate here that embryonic stem cell lines mutant for components
      of the Hedgehog signaling cascade are deficient at generating neurectoderm
      containing embryoid bodies. The embryoid bodies derived from mutant cells are
      also unable to respond to retinoic acid treatment by producing nestin-positive
      neural stem cells, a response observed in cultures of heterozygous cells, and
      contain cores apparently arrested at the primitive ectoderm stage. The mutant
      cultures are also deficient in their capacity to differentiate into mature
      neurons and glia. These data are consistent with a role for Hedgehog signaling in
      generating neurectoderm capable of producing the appropriate neuronal and glial
      progenitors in ES cell culture.

PMID- 14697370
TI  - The current status of digital mammography.
AB  - Digital imaging has shown rapid advances in recent years. Various different
      digital mammography systems are now available for clinical use. Digital
      mammography does have clear advantages over traditional screen film mammography,
      but this is yet to convincingly translate into improved cancer detection rates.
      This review aims to describe the different technologies, introduce concepts
      related to image quality and review the current evidence for the use of digital
      mammography systems in clinical practice. Advanced applications of digital
      mammography such as computer-aided detection (CAD) are also discussed.

PMID- 14697371
TI  - Fibro-osseous lesions of the face and jaws.
AB  - Maxillofacial fibro-osseous lesions (FOL) consists of lesions that differ, with
      the exception of fibrous dysplasia, to those found in the rest of the skeleton.
      FOLs of the face and jaws are cemento-osseous [corrected] dysplasia, fibrous
      dysplasia and cemento-ossifying fibroma. Radiology is central to their diagnosis
      because the pathology for all FOLs is similar, although they range widely in
      behaviour, from dysplasia, hamartoma to benign neoplasia with occasional
      recurrence. Furthermore, once diagnosed the management of each is different. For
      cemento-ossifying dysplasia, this may mean doing nothing, simply because no
      treatment is generally appropriate. Almost all cemento-osseous [corrected]
      fibromas should be treated surgically, whereas cases of fibrous dysplasia are
      treated according to their clinical presentation, ranging from review and follow
      up to surgery necessary to save the patient's sight or reduce deformity. The most
      important and frequent features of the FOLs differential diagnosis is discussed
      with assistance of a flow-chart.

PMID- 14697372
TI  - Imaging of pancreatic adenocarcinoma with emphasis on multidetector CT.
AB  - Pancreatic adenocarcinoma is the fourth most frequent cause of cancer-related
      death. The incidence is increasing and the overall survival has altered little in
      recent years. Moreover, patients usually present late with inoperable disease and
      curative resection by standard pancreatico-duodenectomy (Whipple's procedure) is
      associated with significant morbidity. It should only be attempted in that small
      group of patients lacking radiological evidence of advanced disease. Despite the
      recent advances in body magnetic resonance imaging (MRI) and endoscopic
      ultrasound (EUS), computed tomography (CT) is the mainstay of staging in most
      centres and the recent development of multidetector CT machines (MDCT) has raised
      hope of an improvement in preoperative staging. This review focuses on the CT of
      pancreatic adenocarcinoma with particular emphasis on examination technique and
      on those criteria that determine resectability.

PMID- 14697373
TI  - CT colonography practice in the UK: a national survey.
AB  - AIM: To determine the provision of computed tomography (CT) colonography in UK
      radiology departments. MATERIALS AND METHODS: A questionnaire relating to the
      availability of CT colonography, barriers to implementation, clinical
      indications, technique, and practitioners was posted to clinical directors of UK
      radiology departments. RESULTS: One hundred and thirty-eight departments
      responded. Fifty (36%) offered CT colonography in day-to-day clinical practice.
      Of those that did not, 68 of 87 (64%) cited limited scanner capacity as the main
      barrier. Of the 50 departments offering a service, 39 (78%) offered CT after
      incomplete colonoscopy, 36 (72%), after failed barium enema, and 37 (74%) as an
      alternative to barium enema. Of those offering a service, the number of studies
      performed varied between one per month (38%) to more than one per day (8%). Total
      experience varied between 20 or fewer studies (28%) to more than 300 (12%). Full
      bowel preparation was common (92%), as was dual positioning (90%). Colonography
      was interpreted by radiologists with a subspecialty interest in gastrointestinal
      imaging in 64% of centres offering a service. CONCLUSION: CT colonography is
      widely available in the UK, with approximately one-third of responders offering a
      service. Experience and throughput varies considerably. Limited CT scanner
      capacity is the major barrier to further dissemination.

PMID- 14697374
TI  - Minimal preparation computed tomography instead of barium enema/colonoscopy for
      suspected colon cancer in frail elderly patients: an outcome analysis study.
AB  - AIM: To evaluate the efficacy of minimal preparation computed tomography (MPCT)
      in diagnosing clinically significant colonic tumours in frail, elderly patients.
      MATERIALS AND METHODS: A prospective study was performed in a group of
      consecutively referred, frail, elderly patients with symptoms or signs of
      anaemia, pain, rectal bleeding or weight loss. The MPCT protocol consisted of 1.5
      l Gastrografin 1% diluted with sterile water administered during the 48 h before
      the procedure with no bowel preparation or administration of intravenous contrast
      medium. Eight millimetre contiguous scans through the abdomen and pelvis were
      performed. The scans were double-reported by two gastrointestinal radiologists as
      showing definite (>90% certain), probable (50-90% certain), possible (<50%
      certain) neoplasm or normal. Where observers disagreed the more pessimistic of
      the two reports was accepted. The gold standard was clinical outcome at 1 year
      with positive end-points defined as (1) histological confirmation of CRC, (2)
      clinical presentation consistent with CRC without histological confirmation if
      the patient was too unwell for biopsy/surgery, and (3) death directly
      attributable to colorectal carcinoma (CRC) with/without post-mortem confirmation.
      Negative end-points were defined as patients with no clinical, radiological or
      post-mortem findings of CRC. Patients were followed for 1 year or until one of
      the above end-points were met. RESULTS: Seventy-two patients were included (mean
      age 81; range 62-93). One-year follow-up was completed in 94.4% (n=68). Mortality
      from all causes was 33% (n=24). Five histologically proven tumours were diagnosed
      with CT and there were two probable false-negatives. Results were analysed twice:
      assuming all CT lesions test positive and considering "possible" lesions test
      negative [brackets] (95% confidence intervals): sensitivity 0.88 (0.47-1.0) [0.75
      (0.35-0.97)], specificity 0.47 (0.34-0.6) [0.87 (0.75-0.94)], positive predictive
      value 0.18 [0.43], negative predictive value 0.97 [0.96], positive likelihood
      ratio result 1.6 [5.63], negative likelihood ratio result 0.27 [0.29], kappa 0.31
      [0.43]. Tumour prevalence was 12%. A graph of conditional probabilities was
      generated and analysed. A variety of unsuspected pathology was also found in this
      series of patients. CONCLUSIONS: MPCT should be double-reported, at least
      initially. "Possible" lesions should be ignored. Analysis of the graph of
      conditional probability applied to a group of frail, elderly patients with a high
      mortality from all causes (33% in our study) suggests: (1) if MPCT suggests
      definite or probable carcinoma, regardless of the pre-test probability, the post
      test probability is high enough to warrant further action, (2) frail, elderly
      patients with a low pre-test probability for CRC and a negative MPCT should not
      have further investigation, (3) frail, elderly patients with a higher pre-test
      probability of CRC (such as those presenting with rectal bleeding) and a negative
      MPCT should have either double contrast barium enema (DCBE) or colonoscopy as
      further investigations or be followed clinically for 3-6 months. MPCT was
      acceptable to patients and clinicians and may reveal significant extra-colonic
      pathology.

PMID- 14697375
TI  - Ultrasound-guided percutaneous thermal ablation of hepatocellular carcinoma using
      microwave and radiofrequency ablation.
AB  - AIM: To investigate the therapeutic efficacy of thermal ablation for treatment of
      hepatocellular carcinoma (HCC) using microwave and radiofrequency (RF) energy
      application. MATERIALS AND METHODS: A total of 190 nodules in 97 patients (84
      male, 13 female; mean age 53.4 years, range 24-74 years) with HCC were treated
      with microwave or RF ablation in the last 4 years. The applicators were
      introduced into the tumours under conscious analgesic sedation by intravenous
      administration of fentanyl citrate and droperidol and local anaesthesia in both
      thermal ablation procedures. The patients were then followed up with contrast
      enhanced computed tomography (CT) to evaluate treatment response. Survival was
      analysed using the Kaplan-Meier method. RESULTS: Complete ablation was obtained
      in 92.6% (176/190) nodules. The complete ablation rates were 94.6% (106/112) in
      microwave ablation and 89.7% (70/78) in RF ablation. The complete ablation rates
      in tumours</=2.0, 2.1-3.9 and >/=4.0 cm were 93.1, 93.8 and 86.4%, respectively.
      Local recurrence was found in 9.5% nodules and the rates in tumours</=2.0, 2.1
      3.9 and >/=4.0 cm in diameter were 3.4, 9.9 and 31.8%, respectively. In the
      follow-up period, 7.1% nodules ablated by microwave and 12.8% by RF presented
      local recurrence. The 1, 2 and 3-year distant recurrence-free survivals were
      47.2, 34.9 and 31.0%, respectively. Estimated mean survival was 32 months, and 1,
      2 and 3-year cumulative survivals were 75.6, 58.5, and 50.0%, respectively. One
      and 2 years survivals of Child-Pugh class A, B and C patients were 83.8 and
      70.4%, 78.2 and 53.2%, 36.3 and 27.3%, respectively. CONCLUSION: Thermal ablation
      therapy by means of microwave and RF energy application is an effective and safe
      therapeutic technique for hepatocellular carcinoma. Large tumours can be
      completely ablated, but have a significantly higher risk of local recurrence at
      follow-up.

PMID- 14697377
TI  - How to synthesize evidence for imaging guidelines.
AB  - AIM: To provide guidance on how to gather and evaluate evidence from the
      literature on the efficacy of imaging, using as an example the assessment of the
      role of magnetic resonance imaging (MRI) in the diagnosis of osteomyelitis. This
      method was adopted for evaluating evidence for the musculoskeletal section of the
      5th edition of the Royal College of Radiologists' (RCR) guidelines. MATERIALS AND
      METHODS: A systematic review of the literature published between 1966 and July
      2001 was carried out. Eligible articles described studies in patients with
      suspected osteomyelitis and who were diagnosed using MRI. Search strategies were
      developed to identify relevant imaging studies. Studies included in the
      systematic review were selected using predefined criteria. The sensitivity,
      specificity, accuracy and likelihood ratios for MRI reported in the studies were
      used to evaluate the value of the procedure in osteomyelitis. Where the above
      were not reported, they were calculated by the reviewers. RESULTS: The average
      sensitivity of MRI in osteomyelitis was 91% (range 76-100%), the average
      specificity was 82% (range 65-96%), average accuracy was 88% (range 71-97%), and
      the average positive likelihood ratio was 7.8 (range 2.3-21.1). Four studies
      evaluated the use of MRI in the diagnosis of osteomyelitis in the diabetic foot,
      two in osteomyelitis of the lower extremities, while four each evaluated the use
      of MRI in vertebral osteomyelitis, in the diagnosis of any form of osteomyelitis,
      osteomyelitis in spinal cord-injured patients and in cranial osteomyelitis.
      CONCLUSION: Systematic reviews of literature can be used to obtain evidence on
      the value of imaging procedures. The quality of the studies included in the
      review should always be considered when selecting studies to limit bias. In our
      example, MRI appears sensitive, specific and accurate in the diagnosis of
      osteomyelitis at different sites.

PMID- 14697378
TI  - Evidence against the use of lumbar spine radiography for low back pain.
AB  - AIM: To review abnormalities reported on plain radiographic examination of the
      lumbar spine in patients referred with low back pain by general practitioners.
      Additionally, we evaluated and stratified the prevalence of these abnormalities
      by age. Finally, the diagnostic impact of lumbar spine radiography for the
      diagnosis of degenerative change, fracture, infection and possible tumour, was
      modelled. MATERIALS AND METHODS: A retrospective review of 2007 radiographic
      reports of patients referred with low back pain for lumbar spine radiography to a
      large radiology department was performed. The reports were classified into
      different diagnostic groups and subsequently stratified according to age. The
      potential diagnostic impact of lumbar spine radiography was modelled by using the
      prevalence of conditions studied as pre-test probabilities of disease. RESULTS:
      The prevalence of reported lumbar spine degeneration increased with age to 71% in
      patients aged 65-74 years. The overall prevalence of fracture, possible
      infection, possible tumour was low in our study population: 4, 0.8 and 0.7%,
      respectively. Fracture and possible infection showed no association with age.
      Possible tumour was only reported in patients older than 55 years of age.
      CONCLUSION: Although the prevalence of degenerative changes was high in older
      patients, the therapeutic consequences of diagnosing this abnormality are minor.
      The prevalence of possible serious conditions was very low in all age categories,
      which implies radiation exposure in many patients with no significant lesions.

PMID- 14697379
TI  - In vivo single-voxel proton MR spectroscopy in the differentiation of high-grade
      gliomas and solitary metastases.
AB  - AIM: To determine whether single-voxel proton magnetic resonance spectroscopy
      (1HMRS) could be used to differentiate gliomas from metastases on the basis of
      differences in metabolite levels in the different involved regions. MATERIALS AND
      METHODS: Twenty-two patients (age range from 32 to 62 years, with a median age of
      46.7 years) with a solitary brain tumour (14 gliomas, eight metastases) underwent
      conventional, gadolinium-DTPA enhanced T1-weighted images, and 1HMRS before
      surgical resection. Spectra from the enhancing tumour, the peritumoural region,
      and normal brain were obtained from 1HMRS. A point resolved spectroscopy sequence
      was required for 1HMRS. The metabolites in the spectra include: N-acetylaspartate
      (NAA), choline (CHO), creatine compounds (CR), myo-inositol (MI), lactate (LAC),
      glutamate and glutamine (Glu-n). Relative concentrations of metabolites were
      related to the peak area, and expressed with reference to CR. Student's t-test
      was used to determine whether there was a statistically significant difference in
      relative metabolic ratios between high-grade gliomas and metastases. Meanwhile,
      16 of all 22 patients were re-examined using magnetic resonance imaging (MRI)
      within 6 months of surgical resection. Recurrence was present in three patients
      (two gliomas, one metastasis). RESULTS: Of the 14 patients with gliomas, the
      peaks of NAA were reduced in three cases; the peaks of LAC, which were elevated,
      appeared as typical double-peaks in the peritumoural region in nine cases; the
      peaks of Glu-n, which were also elevated, had a zigzag appearance in seven cases.
      The peaks of MI were increased in the tumoural region in eight cases, and CHO
      levels were elevated in all 14 cases. Of the eight patients with metastases, Glu
      n peaks in the tumoural region in three cases and CHO peaks in the tumoural
      region in four cases were elevated, respectively, while the peaks of CR were
      reduced in three cases, and the peaks of NAA were markedly reduced in four cases
      within the enhancing tumoural region. Elevated CHO levels (CHO-to-CR ratio was
      4.98:1.46, 2.65:0.32) in both the tumoural and peritumoural regions of gliomas
      but not in the metastases (CHO-to-CR ratio was 1.37:0.92, 1.22:0.38), and
      elevated MI levels were present (MI-to-CR ratio was 1.67:0.35) within the
      enhancing foci of gliomas but not in the metastases (MI-to-CR ratio was
      0.89:0.31). The difference was statistically significant (p<0.01). Elevated Glu-n
      and lipid levels were present in all three patients with recurrences. CONCLUSION:
      1HMRS is a useful method in the distinction of these two kinds of tumours. It may
      also may provide useful prognostic information.

PMID- 14697380
TI  - Pathological axillary lymph nodes detected at mammographic screening.
AB  - AIM: To investigate the significance of abnormal axillary lymph nodes detected at
      mammographic screening in the absence of a concomitant breast lesion. METHODS:
      Twenty-three thousand, seven hundred and seven women were screened at the Merrion
      Unit as part of the Irish National Breast Screening Programme ("BreastCheck") in
      the period June 2000 to July 2002. Nine women (0.4 per 1000 women screened) were
      found to have an abnormal axillary lymph node(s) in the absence of a mammographic
      breast lesion and were recalled for assessment. The radiological criteria for
      recall included: size greater than or equal to 15 mm, round or irregular shape,
      increased node density and absence of hilar lucency. Each woman underwent further
      mammographic views, ultrasound examination of axilla and breast, clinical
      examination and lymph node biopsy either by 14G needle core biopsy (NCB) or open
      excision. RESULTS: The final pathological diagnoses in the nine patients were
      oestrogen receptor (OR) positive metastatic breast carcinoma (two patients),
      metastatic malignant melanoma (one patient), malignant lymphoma (two patients),
      caseating granulomatous lymphadenitis suggestive of tuberculosis (one patient),
      and other benign conditions (three patients). CONCLUSION: Abnormal axillary lymph
      nodes, in the absence of an accompanying breast lesion, are rarely identified on
      screening mammogram, but may harbour significant pathology and their presence on
      screening mammogram merits further investigation including biopsy.

PMID- 14697381
TI  - Prevalence of breast arterial calcification in hypertensive patients.
AB  - AIM: To determine the age-specific prevalence of breast arterial calcifications
      in patients with systemic hypertension. METHODS: The mammograms and patient
      records of 2406 women who underwent screening or diagnostic mammography were
      reviewed retrospectively. Mammograms were evaluated for the presence of arterial
      calcification and results were coded. Hypertension was defined as use of anti
      hypertensive agents and diabetes was defined as use of oral hypoglycaemic agents
      or insulin. RESULTS: The prevalence of breast arterial calcification among
      hypertensives (17.6%) was lower than among diabetics (25.4%). The prevalence in
      the non-diabetic, non-hypertensive group was lowest (7.3%). The prevalence
      increased with age in all three groups. The highest prevalence was found in
      diabetics older than 60 years (81.8%). Breast arterial calcification was not
      found among women younger than 40 years. CONCLUSION: Breast arterial
      calcification is associated with hypertension and prevalence increases with age.
      Breast arterial calcification on mammograms may indicate unsuspected hypertension
      especially in non-diabetic patients.

PMID- 14697382
TI  - Uterine artery embolization: an effective treatment for intractable obstetric
      haemorrhage.
AB  - AIM: To present the findings of uterine artery embolization (UAE) in the
      management of obstetric haemorrhage. MATERIALS AND METHODS: From October 1999 to
      February 2003, 10 women with postpartum haemorrhage (n=7) and post-abortion
      haemorrhage with placenta accreta (n=3), were referred to our department for
      pelvic angiography and possible arterial embolization. RESULTS: Angiography
      revealed engorged and tortuous uterine arteries in all patients; and contrast
      medium extravasation in three patients. Eight patients (three with and five
      without detectable active bleeding) then underwent bilateral UAE. Medium-sized
      (250-355 microm) polyvinyl alcohol particles were injected via a coaxial catheter
      into the uterine arteries, followed by gelatin sponge pieces via a 4F Cobra
      catheter. Microcoil devascularization was also performed in the two patients with
      visible, active bleeding. The vaginal bleeding resolved in all patients, without
      any ischaemic complications. At follow-up, all patients who underwent UAE had
      normal menstruation; three of them subsequently gave birth to full-term healthy
      babies. CONCLUSION: Selective UAE by the coaxial method is safe and effective to
      control obstetric haemorrhage, with the potential to preserve fertility.

PMID- 14697383
TI  - Trans-oral embolization of a post-operative duodenocutaneous fistula.

PMID- 14697384
TI  - Osteoblastoma like osteosarcoma.

PMID- 14697385
TI  - Abdominal amyloidosis.

PMID- 14697386
TI  - Imaging in prostate cancer--a reply.

PMID- 14697387
TI  - Mediastinal schwannoma: MR imaging findings of an unusual case presenting as a
      lobulated mass with internal fibrous septa.

PMID- 14697394
TI  - Two brains, one clock.
AB  - A recent study has shown that information about the duration of brief time
      intervals acquired by one side of the brain is readily available to the other
      cerebral hemisphere in a patient in which the corpus callosum and the other
      forebrain commissures have been sectioned. This strongly suggests that the
      internal clock that measures time duration is subcortical, and that its output
      can be easily projected to both hemispheres via subcortical commissures.

PMID- 14697395
TI  - Is speech perception modular or interactive?
AB  - Norris et al. recently reported experimental evidence that listeners learn
      phoneme categories in response to lexical feedback. To reconcile these findings
      with their modular account of speech perception, the authors argue that top-down
      feedback can be used to support phoneme learning, but not to influence on-line
      phonemic processing. We suggest that these findings have broader implications
      than the authors assume, and we discuss potential challenges for integrating a
      modular theory with top-down learning.

PMID- 14697397
TI  - Why is conversation so easy?
AB  - Traditional accounts of language processing suggest that monologue--presenting
      and listening to speeches--should be more straightforward than dialogue--holding
      a conversation. This is clearly not the case. We argue that conversation is easy
      because of an interactive processing mechanism that leads to the alignment of
      linguistic representations between partners. Interactive alignment occurs via
      automatic alignment channels that are functionally similar to the automatic links
      between perception and behaviour (the so-called perception-behaviour expressway)
      proposed in recent accounts of social interaction. We conclude that humans are
      "designed" for dialogue rather than monologue.

PMID- 14697398
TI  - The development of conscious control in childhood.
AB  - Developmental data suggest that the growth of executive function in childhood can
      be understood in terms of the development of consciousness. According to the
      "levels of consciousness" (LOC) model, there are age-related increases in the
      highest degree of self-reflection or LOC that children are able to muster in
      response to situational demands. These increases in LOC with age have
      consequences for the quality of experience, the potential for recall, the
      complexity of children's explicit knowledge structures, and the possibility of
      the conscious control of thought, emotion, and action. The hierarchical LOCs
      identified by this analysis are also useful for understanding the complex
      structure of conscious experience in adults, and they provide a metric for
      measuring the level at which consciousness is operating in specific situations.

PMID- 14697399
TI  - Two hands, one brain: cognitive neuroscience of bimanual skill.
AB  - Bimanual coordination, a prototype of a complex motor skill, has recently become
      the subject of intensive investigation. Whereas past research focused mainly on
      the identification of the elementary coordination constraints that limit
      performance, the focus is now shifting towards overcoming these coordination
      constraints by means of task symbolization or perceptual transformation rules
      that promote the integration of the task components into a meaningful "gestalt".
      The study of these cognitive penetrations into action will narrow the brain-mind
      gap and will facilitate the development of a cognitive neuroscience perspective
      on bimanual movement control.

PMID- 14697400
TI  - Executive dysfunction in autism.
AB  - "Executive function" is an umbrella term for functions such as planning, working
      memory, impulse control, inhibition and mental flexibility, as well as for the
      initiation and monitoring of action. The primacy of executive dysfunction in
      autism is a topic of much debate, as are recent attempts to examine subtypes of
      executive function within autism and other neurodevelopmental disorders that are
      considered to implicate frontal lobe function. This article will review cognitive
      behavioural studies of planning, mental flexibility and inhibition in autism. It
      is concluded that more detailed research is needed to fractionate the executive
      system in autism by assessing a wide range of executive functions as well as
      their neuroanatomical correlates in the same individuals across the lifespan.

PMID- 14697401
TI  - How social perception can automatically influence behavior.
AB  - Do we always know the reasons for our actions? Or is our behavior sometimes
      unknowingly and unintentionally influenced by what we have recently perceived? It
      has been traditionally assumed that the automatic influence of knowledge in
      memory is limited to people's interpretation of the world, and stops short of
      shaping their actual behavior. Researchers in experimental social psychology have
      begun to challenge this assumption by documenting how people's behaviors can be
      unknowingly influenced by knowledge that is incidentally activated in memory
      during social perception. We review findings that suggest that the social
      knowledge that is incidentally activated while reading words or imagining events
      subsequently affects participants' behaviors across a range of ostensibly
      unrelated domains.

PMID- 14697402
TI  - The cognitive foundations of cultural stability and diversity.
AB  - The existence and diversity of human cultures are made possible by our species
      specific cognitive capacities. But how? Do cultures emerge and diverge as a
      result of the deployment, over generations and in different populations, of
      general abilities to learn, imitate and communicate? What role if any do domain
      specific evolved cognitive abilities play in the emergence and evolution of
      cultures? These questions have been approached from different vantage points in
      different disciplines. Here we present a view that is currently developing out of
      the converging work of developmental psychologists, evolutionary psychologists
      and cognitive anthropologists.

PMID- 14697403
TI  - Lethal quercetin-digoxin interaction in pigs.
AB  - Digoxin is a popular cardiac glycoside with very narrow therapeutic range.
      Quercetin is an ubiquitous antioxidant flavonoid. Digoxin is a substrate of P
      glycoprotein (P-gp), a multi-drug efflux transporter, and quercetin was reported
      to be a modulator of P-gp. The aim of this study was to investigate the effect of
      quercetin on the absorption and disposition of digoxin in pigs. Pigs were orally
      given digoxin (0.02 mg/kg) with and without quercetin in crossover designs. The
      blood was collected via jugular vein and fluorescence polarization immunoassay
      was used to determine the serum concentration of digoxin. The pharmacokinetic
      parameters were calculated using WINNONLIN. The paired Student's t-test was used
      for statistical comparison. The coadministration of 50 mg/kg quercetin
      unexpectedly resulted in sudden death of two among three pigs within 30 min after
      digoxin administration. The coadministration of 40 mg/kg quercetin significantly
      elevated the Cmax of digoxin by 413% and increased the AUC0-t by 170%. The
      results indicated that a very serious pharmacokinetic interaction occurred
      between quercetin and digoxin. The concomitant administration of digoxin and
      quercetin or quercetin-containing herbs and dietary supplement should be avoided.

PMID- 14697404
TI  - Peroxynitrite induces arteriolar smooth muscle cells membrane hyperpolarization
      with arteriolar hyporeactivity in rats.
AB  - Peroxynitrite (ONOO-) has been recently known to act as a potent cytotoxin during
      pathogenesis of various diseases. This study aimed to investigate the possible
      effect of ONOO- on the cremaster muscle arteriolar reactivity in response to
      noradrenaline and subsequently determined whether membrane hyperpolarization and
      potassium channel activation were involved in ONOO(-)-induced alteration of
      arteriolar reactivity. The results demonstrated that 1) ONOO- could decrease
      arteriolar reactivity in a time- and concentration-dependent manner with no
      significant alteration of arteriolar diameter; 2) Superfusion with 20 microM ONOO
      over 40 minutes showed slight but not significant influence on the resting
      potential (Em) of arteriolar smooth muscle cells (ASMCs). However, ASMCs
      subjected to 50 or 100 microM ONOO- administration were significantly
      hyperpolarized. As control, treatment with 50 microM decomposed ONOO- or Kreb's
      solution had little effect on the Em of ASMCs; 3) ONOO(-)-induced arteriolar
      hyporeactivity could be greatly reversed by co-administration of KCl and
      partially by TEA. The above results indicated that membrane hyperpolarization and
      potassium channel activation were preferentially responsible for the reduction of
      cremaster muscle arteriolar reactivity after exposure to ONOO-.

PMID- 14697405
TI  - Effect of simvastatin on remodeling of the left ventricle and aorta in L-NAME
      induced hypertension.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been
      shown to prevent or reverse hypertrophy of the LV in several models of left
      ventricular hypertrophy. The aim of the present study was to determine whether
      treatment with simvastatin can prevent hypertension, reduction of tissue nitric
      oxide synthase activity and left ventricular (LV) remodeling in NG-nitro-L
      arginine methyl ester(L-NAME)-induced hypertension. Four groups of rats were
      investigated: control, simvastatin (10 mg/kg), L-NAME (40 mg/kg) and L-NAME +
      simvastatin (in corresponding doses). Animals were sacrificed and studied after 6
      weeks of treatment. The decrease of NO-synthase activity in the LV, kidney and
      brain was associated with hypertension, LV hypertrophy and fibrosis development
      and remodeling of the aorta in the L-NAME group. Simvastatin attenuated the
      inhibition of NO-synthase activity in kidney and brain, partly prevented
      hypertension development and reduced the concentration of coenzyme Q in the LV.
      Nevertheless, myocardial hypertrophy, fibrosis and enhancement of DNA
      concentration in the LV, and remodeling of the aorta were not prevented by
      simultaneous simvastatin treatment in the L-NAME treated animals. We conclude
      that the HMG-CoA reductase inhibitor simvastatin improved nitric oxide production
      and partially prevented hypertension development, without preventing remodeling
      of the left ventricle and aorta in NO-deficient hypertension.

PMID- 14697406
TI  - Effects of endogenous carbon monoxide on collagen synthesis in pulmonary artery
      in rats under hypoxia.
AB  - To study the role of endogenous carbon monoxide (CO) in collagen metabolism
      during hypoxic pulmonary vascular remodeling, a total of 18 Wistar rats were used
      in the study and they were randomly divided into three groups: hypoxia group (n =
      6), hypoxia with zinc protoporphyrin-IX (ZnPP-IX) group (n = 6) and control group
      (n = 6). The measurement of mean pulmonary artery pressure (mPAP) and
      carboxyhemoglobin (HbCO) formation in lung tissue homogenates was measured. A
      morphometric analysis of pulmonary vessels was performed, in which the percentage
      of muscularized arteries (MA); partially muscularized arteries (PMA) and
      nonmuscularized arteries (NMV) in small and median pulmonary vessels, relative
      medial thickness (RMT) and relative medial area (RMA) of pulmonary arteries were
      analyzed. Collagen type I and III and transforming growth factor-beta3 (TGF
      beta3) expressions were detected by immunohistochemical assay. The expressions of
      procollagen type I and III and TGF-beta3 mRNA were detected by in situ
      hybridization. The results showed that ZnPP-IX significantly increased mPAP and
      markedly decreased HbCO formation in lung tissue homogenates in rats under
      hypoxia (P < 0.01). In the hypoxia rats treated with ZnPP-IX, the percentage of
      muscularized arteries of small and median pulmonary vessels was obviously
      increased, and RMT and RMA of intra-acinar muscularized pulmonary arteries were
      markedly increased compared with hypoxic rats. Ultrastructural changes, such as
      hyperplasia and hypertrophy of endothelial cells (ECs) and smooth muscle cells
      (SMCs) and the increased number of SMCs in synthetic phenotype were found in
      intra-acinar pulmonary muscularized arteries of hypoxic rats treated with ZnPP
      IX. Meanwhile, ZnPP-IX promoted the expression of collagen type I and III and TGF
      beta3 protein in pulmonary arteries of rats under hypoxia (P < 0.01).
      Furthermore, ZnPP-IX elevated obviously the expressions of procollagen type I and
      III mRNA, and TGF-beta3 mRNA in pulmonary arteries of rats under hypoxia (P <
      0.01). The results of this study suggested that ZnPP-IX played an important role
      in promoting collagen synthesis in pulmonary arteries of rats with hypoxic
      pulmonary structural remodeling by increasing the expression of TGF-beta3. The
      above findings also suggested a possible role of endogenous CO in the
      pathogenesis of chronic hypoxic pulmonary hypertension.

PMID- 14697407
TI  - Adrenalectomy affects pain behavior of rats after formalin injection.
AB  - Stressful stimuli can activate the hypothalamo-pituitary-adrenal-axis and the
      endogenous opioid system. In addition, corticosterone and opioid release might
      cause analgesia. This rat study used adrenalectomy for corticosterone withdrawal
      and naloxone administration for opioid antagonism in order to study pain behavior
      and hypophyseal hormone release in the plasma after a formalin test. Twelve days
      before the formalin testing, male Sprague Dawley rats underwent adrenalectomy or
      sham-adrenalectomy, and non-operated rats were used as reference. The number of
      flinches and the duration of licking or biting behavior were measured during the
      early and late phase. In reference and sham-operated rats, injection of formalin
      5% resulted in a marked pain behavior in the early and late phase with
      significant increases in ACTH and corticosterone plasma levels. In
      adrenalectomized rats, pain behavior was decreased during both phases. Naloxone,
      administered before the late phase, did not alter pain behavior in sham or
      reference rats, whereas in adrenalectomized rats pain reactivity returned to
      those levels observed in reference rats. Beta-endorphin plasma levels above the
      detection limit were more frequently found in adrenalectomized rats. Thyrotropin
      and prolactin levels were not different between studied groups. We speculate that
      the observed reduced pain behavior in adrenalectomized rats after formalin, is
      the result of an increased production of pro-opiomelanocortin, the pro-drug of
      both adrenocorticotrophic hormone and beta-endorphin.

PMID- 14697408
TI  - Levetiracetam protects against kainic acid-induced toxicity.
AB  - We investigated the Levetiracetam (LVT) ability to protect the brain against
      kainic acid (KA) induced neurotoxicity. Brain injury was induced by
      intraperitoneal administration of KA (10 mg/kg). Sham brain injury rats were used
      as controls. Animals were randomized to receive either LVT (50 mg/kg) or its
      vehicle (1 ml/kg) 30 min. before KA administration. Animals were sacrificed 6
      hours after KA injection to measure brain malonildialdehyde (MDA), glutathione
      levels (GSH) and the mRNA for interleukin-1beta (IL-1beta) in the cortex and in
      the diencephalon. Behavioral changes were also monitored. Intraperitoneal
      administration of LVT decreased significantly MDA in the cortex (KA + vehicle =
      0.25 +/- 0.03 nmol/mg protein; KA + LVT = 0.13 +/- 0.01 nmol/mg protein; P <
      0.005), and in the diencephalons (KA + vehicle = 1,01 +/- 0.2 nmol/mg protein; KA
      + LVT = 0,33 +/- 0,08 nmol/mg protein; P < 0.005), prevented the brain loss of
      GSH in both cortex (KA + vehicle = 5 +/- 1 micromol/g protein; KA + LVT = 15 +/-
      2 micromol/g protein; P < 0.005) and diencephalons (KA + vehicle = 9 +/- 0.8
      micromol/g protein; KA + LVT = 13 +/- 0.3 micromol/g protein; P < 0.05), reduced
      brain IL-1beta mRNA and markedly controlled seizures. Histological analysis
      showed a reduction of cell damage in LVT treated samples. The present data
      indicate that LVT displays neuro-protective effects against KA induced brain
      toxicity and suggest that these effects are mediated, at least in part, by
      inhibition of lipid peroxidation.

PMID- 14697409
TI  - Age-related changes of serum lipoprotein oxidation in rats.
AB  - Oxidation of low-density lipoprotein (LDL) may be a prelude to atherogenesis and
      directly age related. To assess whether there may be relationship between age and
      plasma lipoprotein (LP) oxidation, we studied copper-mediated LP oxidation
      isolated from the blood of 2 months, 7 months, and 15 months old rats. We
      determined whether the susceptibility of LP to oxidation might be related to
      vitamin C levels in serum, vitamin E levels in LP, or the total antioxidant
      capacity (TAC) of serum or LP. Serum vitamin C content was inversely related to
      age, malondialdehyde (MDA) propagation rate, and maximum change of MDA
      concentrations. However, there were no significant relationships between age and
      serum TAC, LP TAC, serum vitamin E, or the ratio of LP vitamin E to serum vitamin
      C content. The lag phase of MDA formation was significantly decreased with age
      and the ratio of LP vitamin E content to serum vitamin C content, increased with
      age. Maximum change of MDA concentration was positively correlated with the ratio
      of LP vitamin E contents to serum vitamin C concentration. Thus, as the rat ages,
      vitamin C status decreases with an increased LP susceptibility to oxidation. It
      is tempting to speculate that enhanced LP oxidation in older rats may reflect a
      reduced amount of recycling of LDL vitamin E by serum vitamin C.

PMID- 14697410
TI  - Involvement of K+ channels and calcium-dependent pathways in the action of T3 on
      amino acid accumulation and membrane potential in Sertoli cells of immature rat
      testis.
AB  - The purpose of this study was to investigate the involvement of calcium in K+
      currents and its effects on amino acid accumulation and on the membrane potential
      regulated by tri-iodo-L-thyronine (T3) in Sertoli cells. Immature rat testes were
      pre-incubated for 30 min in Krebs-Ringer bicarbonate buffer and incubated for 60
      min in the presence of [14C]methylaminoisobutyric acid with and without T3 or T4
      (dose-response curve). Specific channel blockers or chelating agents were added
      at different concentrations during pre-incubation and incubation periods to study
      the basal amino acid accumulation and a selected concentration of each drug was
      chosen to analyze the influence on the stimulatory hormone action. All amino acid
      accumulation experiments were carried out in a Dubnoff metabolic incubator at 32
      degrees C, pH 7.4 and gassed with O2:CO2 (95:5; v/v). Seminiferous tubules from
      immature Sertoli cell-enriched testes were used for the electrophysiology
      experiments. Intracellular recording of the Sertoli cells was carried out in a
      chamber perfused with KRb with/without T3, T4 or blockers and the membrane
      potential was monitored. We found that T3 and T4 stimulated alpha-[1-14C]
      methylaminoisobutyric acid accumulation in immature rat testes and induced a
      membrane hyperpolarization in Sertoli cells. The action of T3 on amino acid
      accumulation and on the hyperpolarizing effect was inhibited by the K(+)-ATP
      channel blocker tolbutamide as well as the voltage-dependent Ca2+ channel blocker
      verapamil. These results clearly demonstrate for the first time the existence of
      an ionic mechanism related to Ca2+ and K+ fluxes in the rapid, nongenomic action
      of T3.

PMID- 14697411
TI  - Hyaluronic acid and chondroitin-4-sulphate treatment reduces damage in carbon
      tetrachloride-induced acute rat liver injury.
AB  - Oxidative stress is involved in the pathogenesis of chemically mediated liver
      injury. Since glycosaminoglycans possess antioxidant activity, the aim of this
      work was to assess the protective effects of hyaluronic acid and chondroitin-4
      sulphate treatment in a model of carbon tetrachloride-induced liver injury. Liver
      damage was induced in male rats by an intraperitoneal injection of carbon
      tetrachloride (1 ml/kg in vegetal oil). Serum alanine aminotransferase and
      aspartate aminotransferase, hepatic malondialdehyde, plasma TNF-alpha, hepatic
      reduced glutathione and catalase, and myeloperoxidase, an index of
      polymorphonuclear infiltration in the jeopardised hepatic tissue, were evaluated
      24 h after carbon tetrachloride administration. Carbon tetrachloride produced a
      marked increase in serum alanine aminotransferase and aspartate aminotransferase
      activities, primed lipid peroxidation, enhanced plasma TNF-alpha levels, induced
      a severe depletion of reduced glutathione and catalase, and promoted neutrophil
      accumulation. Intraperitoneal treatment of rats with hyaluronic acid (25 mg/kg)
      or chondroitin-4-sulphate (25 mg/kg) failed to exert any effect in the considered
      parameter, while the combination treatment with both glycosaminoglycans (12,5 +
      12,5 mg/kg) decreased the serum levels of alanine aminotransferase and aspartate
      aminotransferase, inhibited lipid peroxidation by reducing hepatic
      malondialdehyde, reduced plasma TNF-alpha, restored the endogenous antioxidants,
      and finally decreased myeloperoxidase activity. These results suggest that
      hyaluronic acid and chondroitin-4-sulphate possess a different antioxidant
      mechanism and consequently the combined administration of both glycosaminoglycans
      exerts a synergistic effect with respect to the single treatment.

PMID- 14697412
TI  - Conjugation metabolism of acetaminophen and bilirubin in extrahepatic tissues of
      rats.
AB  - An anhepatic rat model was used to explore the extrahepatic conjugating
      metabolism of acetaminophen and serum bilirubin. The recovery of glucuronide- and
      sulfate-acetaminophen was 47.5% in normal control and 13.4% in model rats in the
      urine collected for 6 h after administration of acetaminophen 20 mg kg(-1).
      Following the increase of acetaminophen dose to 150 mg kg(-1), the recovery of
      urinary glucuronide-acetaminophen increased by 53.9% in normal control; but it
      decreased by 36.4% in model rats. In contrast to normal control, the pretreatment
      with phenobarbital did not affect acetaminophen and its metabolite levels in
      plasma and urine in model rats. After the establishment of anhepatic model the
      serum direct bilirubin rose dramatically. Urinary bilirubin test was positive in
      model rats, but not in normal control. No changes were observed in serum total
      bilirubin and ratio of direct/total bilirubin after the pretreatment with
      ranitidine or phenobarbital 50 mg kg (-1), i.p. for 5 days in model rats. The
      results indicate that the glucuronide- and sulfate-acetaminophen formed in the
      extrahepatic tissues of model rats is 28.2% of normal control, serum free
      bilirubin can be transformed into conjugated bilirubin in extrahepatic tissues,
      and the regulation mechanism of phase II conjugating enzymes is different between
      the hepatic and extrahepatic tissues.

PMID- 14697413
TI  - Where are the at-risk cervical nodes?

PMID- 14697414
TI  - Is there a favorable subset of patients with prostate cancer who develop
      oligometastases?
AB  - OBJECTIVE: To analyze, retrospectively, the patterns and behavior of metastatic
      lesions in prostate cancer patients treated with external beam radiotherapy and
      to investigate whether patients with < or =5 lesions had an improved outcome
      relative to patients with >5 lesions. METHODS AND MATERIALS: The treatment and
      outcome of 369 eligible patients with Stage T1-T3aN0-NXM0 prostate cancer were
      analyzed during a minimal 10-year follow-up period. All patients were treated
      with curative intent to a mean dose of 65 Gy. The full history of any metastatic
      disease was documented for each subject, including the initial site of
      involvement, any progression over time, and patient survival. RESULTS: The
      overall survival rate for the 369 patients was 75% at 5 years and 45% at 10
      years. The overall survival rate of patients who never developed metastases was
      90% and 81% at 5 and 10 years, respectively. However, among the 74 patients (20%)
      who developed metastases, the survival rate at both 5 and 10 years was
      significantly reduced (p <0.0001). The overall survival rate for patients who
      developed bone metastases was 58% and 27% at 5 and 10 years, respectively, and
      patients with bone metastases to the pelvis fared worse compared with those with
      vertebral metastases. With regard to the metastatic number, patients with < or =5
      metastatic lesions had superior survival rates relative to those with >5 lesions
      (73% and 36% at 5 and 10 years vs. 45% and 18% at 5 and 10 years, respectively; p
      = 0.02). In addition, both the metastasis-free survival rate and the interval
      measured from the date of the initial diagnosis of prostate cancer to the
      development of bone metastasis were statistically superior for patients with < or
      =5 lesions compared with patients with >5 lesions (p = 0.01 and 0.02,
      respectively). However, the survival rate and the interval from the date of
      diagnosis of bone metastasis to the time of death for patients in both groups
      were not significantly different, statistically (p = 0.17 and 0.27,
      respectively). CONCLUSIONS: Patients with < or =5 metastatic sites had
      significantly better survival rates than patients with >5 lesions. Because
      existing sites of metastatic disease may be the primary sites of origin for
      additional metastases, our findings suggest that early detection and aggressive
      treatment of patients with a small number of metastatic lesions is worth testing
      as an approach to improving long-term survival.

PMID- 14697415
TI  - What defines intermediate-risk prostate cancer? Variability in published
      prognostic models.
AB  - PURPOSE: To assess the efficacy of a variety of prognostic models in the
      definition of intermediate-risk prostate cancer and to compare them to our own
      empiric model. METHODS AND MATERIALS: Two hundred fifty-six consecutive men with
      prostate adenocarcinoma treated with external beam radiotherapy alone were
      studied. Biochemical failure (defined as 3 consecutive PSA rises or the
      initiation of androgen deprivation therapy) was examined using univariate,
      multivariate, and recursive partitioning analyses. The risk classification model
      used in our department was then compared to a number of published models to
      assess the relative performance of each in discriminating risk groups. RESULTS:
      At a median follow-up of 62.4 months, the 5-year Biochemical failure-free
      survival (bFFS) was 46.8% for the overall group. This relates to 5-year bFFS of
      77.8%, 51.1%, and 33.8% based on our institutional criteria for low-,
      intermediate-, and high-risk features, respectively. All the models examined
      showed an outcome group with a comparatively similar poor outcome when applied to
      our data. Large variation was seen in the intermediate-risk groups, with 5-year
      bFFS ranging from 38.1% to 51.1%. Good risk categories had similar large
      variations. All published models showed inability to delineate three
      significantly different outcome groups. Recursive partitioning analysis derived
      categories based on combinations of PSA (with cutpoints at 42.4, 20, and 10.6
      ng/mL) and Gleason score (with cutpoints at 2-6 and 7-10) only. CONCLUSIONS:
      Large variations in the relative performance of a number of prognostic models are
      shown when applied to our local data. The prognostic efficacy of PSA and biopsy
      Gleason score is reiterated, although other factors will need to be explored to
      further improve the performance of prognostic models, particularly in defining
      the intermediate-risk subset of prostate cancer.

PMID- 14697416
TI  - Perineural invasion is associated with increased relapse after external beam
      radiotherapy for men with low-risk prostate cancer and may be a marker for
      occult, high-grade cancer.
AB  - PURPOSE: To investigate the risk of postradiotherapy prostate-specific antigen
      (PSA) failure on the basis of pretreatment risk factors in prostate cancer
      patients with and without perineural invasion (PNI) in prostate biopsy specimens
      and to explain the observation that otherwise low-risk patients with PNI
      experience decreased freedom from PSA failure after external beam radiotherapy
      (RT). METHODS AND MATERIALS: The study cohort consisted of 381 patients who
      underwent RT between 1989 and 2000 for clinically localized prostate cancer. A
      single genitourinary pathologist scored the absence or presence of PNI on all
      prostate biopsy specimens. Patients were divided into low-, intermediate- and
      high-risk subgroups on the basis of their 1992 American Joint Committee on Cancer
      T-stage, pretreatment PSA level, and Gleason score. Cox regression uni- and
      multivariate analyses were performed to evaluate whether the presence or absence
      of PNI in the biopsy specimen was a predictor of the time to post-RT PSA failure
      for patients in each pretreatment risk group. PSA failure was defined using the
      American Society for Therapeutic Radiology and Oncology consensus definition.
      Actuarial PSA failure-free survival was estimated using the Kaplan-Meier method,
      and comparisons were performed using the log-rank test. RESULTS: Cox regression
      univariate analysis revealed that PNI was a significant predictor of the time to
      PSA failure in the low-risk (p = 0.04) and high-risk (p = 0.03) cohorts. The 5
      year PSA failure-free survival rate was 50% vs. 80% (p = 0.04) in low-risk
      patients, 70% vs. 75% (p = 0.72) in intermediate-risk patients, and 29% vs. 53%
      (p = 0.03) in high-risk patients with and without PNI, respectively. Cox
      regression multivariate analysis within the high-risk group revealed that a PSA
      level > or =20 ng/mL (p = 0.01) and Gleason score > or =8 (p = 0.02), but not
      PNI, were the only significant predictors of the time to PSA failure after RT.
      However, an association was found between the presence of PNI in the needle
      biopsy specimen and a biopsy Gleason score of 8-10 (p = 0.06). The association
      was stronger between the presence of PNI in the needle biopsy specimen and a
      biopsy Gleason score of 7-10 (p = 0. 033). CONCLUSION: A decrement in PSA outcome
      after RT for low-risk patients with PNI-positive biopsy specimens was found. The
      association between PNI and high Gleason score provides a possible explanation
      for the loss of statistical significance of PNI in the Cox regression
      multivariate analysis of the high-risk cohort. The data suggest that PNI found in
      the biopsy specimen of an otherwise low-risk patient predicts for occult high
      grade disease that is missed owing to the sampling error associated with prostate
      biopsy. The association between PNI and a high Gleason score argues for the use
      of more aggressive therapy, such as hormonal therapy with RT and/or dose
      escalation, in these select patients.

PMID- 14697417
TI  - Radical prostatectomy, external beam radiotherapy <72 Gy, external beam
      radiotherapy > or =72 Gy, permanent seed implantation, or combined seeds/external
      beam radiotherapy for stage T1-T2 prostate cancer.
AB  - PURPOSE: To review the biochemical relapse-free survival (bRFS) rates after
      treatment with permanent seed implantation (PI), external beam radiotherapy
      (EBRT) <72 Gy (EBRT <72), EBRT > or =72 Gy (EBRT > or =72), combined seeds and
      EBRT (COMB), or radical prostatectomy (RP) for clinical Stage T1-T2 localized
      prostate cancer treated between 1990 and 1998. METHODS AND MATERIALS: The study
      population comprised 2991 consecutive patients treated at the Cleveland Clinic
      Foundation or Memorial Sloan Kettering at Mercy Medical Center. All cases had
      pretreatment prostate-specific antigen (iPSA) levels and biopsy Gleason scores
      (bGSs). Neoadjuvant androgen deprivation for < or =6 months was given in 622
      cases (21%). No adjuvant therapy was given after local therapy. RP was used for
      1034 patients (35%), EBRT <72 for 484 (16%), EBRT > or =72 for 301 (10%), PI for
      950 (32%), and COMB for 222 patients (7%). The RP, EBRT <72, EBRT > or =72, and
      154 PI patients were treated at Cleveland Clinic Foundation. The median radiation
      doses in EBRT <72 and EBRT > or =72 case was 68.4 and 78.0 Gy, respectively. The
      median follow-up time for all cases was 56 months (range 12-145). The median
      follow-up time for RP, EBRT <72, EBRT > or =72, PI, and COMB was 66, 75, 49, 47,
      and 46 months, respectively. Biochemical relapse was defined as PSA levels >0.2
      for RP cases and three consecutive rising PSA levels (American Society for
      Therapeutic Radiology Oncology consensus definition) for all other cases. A
      multivariate analysis for factors affecting the bRFS rates was performed using
      the following variables: clinical T stage, iPSA, bGS, androgen deprivation, year
      of treatment, and treatment modality. The multivariate analysis was repeated
      excluding the EBRT <72 cases. RESULTS: The 5-year bRFS rate for RP, EBRT <72,
      EBRT > or =72, PI, and COMB was 81%, 51%, 81%, 83%, and 77%, respectively (p
      <0.001). The 7-year bRFS rate for RP, EBRT <72, EBRT > or =72, PI, and COMB was
      76%, 48%, 81%, 75%, and 77%, respectively. Multivariate analysis, including all
      cases, showed iPSA (p <0.001), bGS (p <0.001), year of therapy (p <0.001), and
      treatment modality (p <0.001) to be independent predictors of relapse. Because
      EBRT <72 cases had distinctly worse outcomes, the analysis was repeated after
      excluding these cases to discern any differences among the other modalities. The
      multivariate analysis excluding the EBRT <72 cases revealed iPSA (p <0.001), bGS
      (p <0.001), and year of therapy (p = 0.001) to be the only independent predictors
      of relapse. Treatment modality (p = 0.95), clinical T stage (p = 0.09), and
      androgen deprivation (p = 0.56) were not independent predictors for failure.
      CONCLUSION: The biochemical failure rates were similar among PI, high-dose (> or
      =72 Gy) EBRT, COMB, and RP for localized prostate cancer. The outcomes were
      significantly worse for low-dose (<72 Gy) EBRT.

PMID- 14697418
TI  - Predictors of preferences and utilities in men treated with 3D-CRT for prostate
      cancer.
AB  - PURPOSE: To assess the preferences and utilities for prostate cancer health state
      scenarios of men treated with three-dimensional conformal radiotherapy and the
      predictors of treatment preferences. METHODS AND MATERIALS: The preferences and
      utilities for probabilistic health states of impotence and incontinence
      associated with prostate cancer therapies were elicited from prostate cancer
      registry participants using a modified time trade-off interview.
      Sociodemographic, disease, and treatment characteristics, as well as quality-of
      life scores, were assessed to determine the predictors of preferences. RESULTS:
      Fifty-seven men treated with three-dimensional conformal radiotherapy completed
      the time trade-off interview. Of these men, 83% had Stage T1-T2 and 30% were
      receiving hormonal therapy. The utilities followed a linear trend with declining
      scores for increasing risk of poorer health states. Men showed an increased
      preference for health states associated with radiotherapy compared with surgery
      or hormonal therapy. Univariate predictors of preference included income and
      marital status. Multivariate predictors of preferences included more aggressive
      therapy and better prognostic indicators. Current quality-of-life scores in terms
      of global, sexual, or urinary function were poor predictors of preferences.
      CONCLUSION: Preference elicitation can assist in decision-making, and
      understanding the predictors of patient preferences can assist in identifying
      factors that may increase patient perceptions of poorer outcomes.

PMID- 14697419
TI  - Short-term androgen deprivation and PSA doubling time: their association and
      relationship to disease progression after radiation therapy for prostate cancer.
AB  - PURPOSE: The goal of this study was to investigate the relationship between PSA
      doubling time (PSADT) and initial management of prostate cancer with short-term
      androgen deprivation (STAD) and the impact of these factors on disease
      progression after radiation therapy. METHODS AND MATERIALS: Between May 1989 and
      October 1998, 284 patients treated with 3D-CRT experienced biochemical failure
      (BF) as defined under the ASTRO consensus statement. All patients had sufficient
      follow-up data for PSADT calculations. Linear regression was used to assess
      predictors of PSADT among STAD, time to biochemical failure (TTBF), Gleason
      Score, tumor stage, dose, posttreatment PSA nadir, pretreatment PSA, and age. A
      composite covariate was created from the various combinations of factors found to
      be predictive of PSADT. The composite covariate was then included, along with
      PSADT and the factors previously mentioned, in proportional hazards modeling of
      freedom from distant metastasis (FDM), cause-specific survival (CSS), and overall
      survival (OS). RESULTS: Fifty-four (19%) patients developed distant metastasis,
      20 (7%) died of prostate cancer, and 53 (19%) died of any cause. The median PSADT
      was 12 months. Predictors of a longer PSADT were TTBF >12 months, Gleason Score 2
      6, and STAD. An ordinal composite covariate was created with eight levels on the
      basis of the magnitude of observed mean PSADT within the eight possible
      combinations of the three dichotomized predictors. The most significant predictor
      of higher FDM rates in Cox modeling was the composite covariate, followed by
      longer PSADT, STAD, lower PSA nadir, higher RT dose, and Gleason Score 2-6.
      Predictors of higher CSS rates were lower nadir, longer PSADT, T1/T2ab tumors,
      the composite covariate, and STAD. The most significant predictor of a higher OS
      rate was STAD, followed by longer PSADT, younger age at diagnosis, the composite
      covariate, lower nadir, and T1/T2ab tumors. CONCLUSIONS: Longer TTBF, Gleason
      Score 2-6 tumors, and STAD were predictive of longer PSADT. Even after adjusting
      for these factors in the capacity of their predictive properties for PSADT, STAD
      and observed PSADT continued to be significant independent predictors of FDM,
      CSS, and OS. STAD appears to have a pronounced impact on disease progression,
      probably the result partly of the prolongation of PSADT.

PMID- 14697420
TI  - The role of hemoglobin concentration in clinically localized prostate cancer
      treated with radical radiotherapy +/- neoadjuvant androgen deprivation.
AB  - PURPOSE: Serum hemoglobin level (Hb) is a significant determinant of treatment
      outcome after radical radiotherapy (RT) for several cancer types, but its
      importance in prostate cancer is not well established. METHODS AND MATERIALS: Two
      treatment-specific cohorts of men with localized prostate cancer (T1-4, Nx/N0,
      M0) were analyzed. Seven hundred six men who received radical RT at Princess
      Margaret Hospital between 1987 and 2000 comprise the RT-alone cohort, of whom 536
      had a pre-RT Hb. Six hundred fifty-eight men received 3-6 months' neoadjuvant
      androgen deprivation (NAD) and radical RT at Royal Marsden Hospital between 1989
      and 2000 and comprise the NAD + RT cohort, of whom 475 had a pre-NAD Hb and 513 a
      pre-RT Hb. Time to biochemical failure (TTBF) was the primary end point.
      Univariate and multivariate analyses using the Cox proportional hazards
      regression model were used for each data set independently to study the
      prognostic role of pre-RT Hb, pre-NAD Hb, nadir Hb (lowest Hb during RT), Hb
      decrement (pre-NAD Hb - pre-RT Hb), Gleason score, presenting PSA, and T stage.
      RESULTS: On univariate analysis, no significant association was seen between TTBF
      and any of the Hb variables for either data set. On multivariate analysis, TTBF
      was associated with presenting PSA (p < 0.001), Gleason score (p < 0.01), and
      (for the NAD + RT data set) T stage (p < 0.001), but not pre-NAD Hb (p = 0.24) or
      pre-RT Hb (p > 0.3). CONCLUSION: Hemoglobin level is not an important determinant
      of RT outcome in localized prostate cancer.

PMID- 14697421
TI  - Impact of neoadjuvant androgen ablation and other factors on late toxicity after
      external beam prostate radiotherapy.
AB  - PURPOSE: To evaluate the late toxicity profile of prostate cancer patients
      treated with external beam radiotherapy, to investigate the possible risk factors
      for late toxicity, and to determine whether neoadjuvant androgen ablation (NAA)
      is a factor. METHODS AND MATERIALS: The study population consisted of 1192
      patients with > or =24 months' follow-up. Late GI and GU toxicities were scored
      with a modified Radiation Therapy Oncology Group/Subjective, Objective,
      Management, and Analytic scale. All patients were treated with external beam
      radiotherapy (52.5 Gy in 20 fractions to 72 Gy in 36 fractions), using either
      conventional or three-dimensional conformal techniques. Of the 1192 patients, 40%
      received NAA (median 5 months). Risk factors investigated on multivariate
      analysis were age, past medical history, use of pelvic fields, dose,
      fractionation, use and duration of neo- and adjuvant androgen ablation, and acute
      toxicity (Grade 2 or greater). RESULTS: The median follow-up for the group was 49
      months (range 24-105). The incidence of late Grade 2-3 GI or GU toxicity was 30%
      at 5 years (GI 12% and GU 20%). The incidence of late Grade 3 GI or GU toxicity
      was 8% at 5 years (GI 2.7% and GU 5.5%). No Grade 4 toxicity occurred. The risk
      factors of significance in relation to the development of late Grade 3 GU
      toxicity were coexisting GU disease (p = 0.02), prior transurethral resection of
      the prostate or transurethral resection of bladder tumor (p <0.0001), and
      presence of acute GU toxicity (p = 0.012). For late Grade 3 GI toxicity, short
      term (< or =2 months) NAA (p = 0.0002) and coexisting GI disease (p = 0.017) were
      risk factors. CONCLUSION: Short-term (< or =2 months) NAA, but not longer
      durations of NAA, increases the risk of developing Grade 3 GI late toxicity. The
      possible mechanism of this phenomenon is unclear.

PMID- 14697422
TI  - Influence of hormonal therapy on late rectal function after permanent prostate
      brachytherapy with or without supplemental external beam radiotherapy.
AB  - PURPOSE: Recent clinical studies have reported a relationship between the use of
      hormonal therapy and degradation in rectal function after external beam
      radiotherapy. Using a patient-administered quality-of-life instrument, we
      evaluated the effect of hormonal therapy on late rectal function after permanent
      prostate brachytherapy with or without supplemental external beam radiotherapy.
      METHODS AND MATERIALS: A total of 189 patients were mailed the Rectal Function
      Assessment Score (R-FAS), which consists of nine questions (score range 0-27,
      with higher scores indicative of poorer bowel function). Of the 189 surveys sent
      out, 187 (98.4%) were returned. Of the 187 patients, 149 (79.7%) were hormone
      naive, and 38 (20.3%) had received hormonal manipulation (median duration 4
      months, range 3-36). The median follow-up for the entire group was 66.3 months.
      The effect of hormonal therapy on bowel function was evaluated by comparing the R
      FAS scores across time, by each of the individual nine questions, and by means of
      a summary question evaluating the patient's perception of overall bowel function.
      The two groups were also evaluated in terms of clinical, treatment, and
      dosimetric parameters, including follow-up, age, Gleason score, clinical stage,
      pretreatment prostate-specific antigen level, number of pretreatment bowel
      movements/d, prostate volume, and rectal dosimetry. RESULTS: The two groups were
      well matched in all clinical, treatment, and dosimetric parameters, except the
      patients receiving hormonal therapy had a statistically shorter follow-up (63.9
      vs. 69.4 months, p <0.001) and higher pretreatment prostate-specific antigen
      level (12.0 vs. 9.8 ng/mL, p = 0.024). The R-FAS scores for the hormone-naive and
      hormonally manipulated patients were comparable (3.76 vs. 4.55, p = 0.083). In
      terms of the nine individual R-FAS questions, no statistically significant
      difference was reported for any question when stratified by hormonal status,
      including rectal bleeding (p = 0.735). Only 12% and 13% of hormone-naive and
      hormonally manipulated patients, respectively, reported bowel function to be
      worse after implantation. With time, a trend for improvement in the R-FAS was
      noted in both cohorts. CONCLUSION: After permanent prostate brachytherapy, no
      statistically significant difference in bowel habits was discerned when
      stratified by hormonal status. In addition, only 12% of brachytherapy patients
      reported deterioration in bowel function after implantation.

PMID- 14697423
TI  - Spontaneous improvement in late rectal mucosal changes after radiotherapy for
      prostate cancer.
AB  - PURPOSE: To describe the natural history of mucosal changes, in particular the
      development of telangiectases in the rectum, after radiotherapy (RT) for prostate
      cancer. METHODS AND MATERIALS: Twenty patients undergoing local-field,
      nonconformal RT for prostate cancer underwent flexible sigmoidoscopy every 6
      months for up to 3 years after RT completion. Telangiectasis was scored as
      absent, single, multiple, or multiple confluent. The site and circumferential
      extent were also documented. The patients filled in a diary to document the
      symptoms they were experiencing, including rectal bleeding. RESULTS: Of the 20
      patients, 12 developed multiple telangiectases, and 10 of these had rectal
      bleeding, which in all cases was mild. Telangiectasis was most commonly seen
      between 4 (anorectal junction) and 8 cm from the anal verge. In 5 patients, 4 of
      whom had multiple telangiectases, spontaneous resolution occurred. CONCLUSION:
      Late radiation effects in the rectum do not appear to be permanent in all cases.
      This first prospective prolonged evaluation may provide an explanation for the
      observation that rectal bleeding resolves in a large proportion of patients with
      mild symptoms after RT. The reasons for improvement in the late radiation changes
      in the rectum compared with the permanent changes seen in organs such as the skin
      are unknown.

PMID- 14697424
TI  - Effect of transurethral resection on urinary quality of life after permanent
      prostate brachytherapy.
AB  - PURPOSE: To determine the effect of transurethral resection on urinary function
      after permanent prostate brachytherapy using a validated, patient-administered,
      quality-of-life (QOL) instrument. METHODS AND MATERIALS: Twenty-seven consecutive
      brachytherapy patients with clinical T1b-T2b (1997 American Joint Commission on
      Cancer) prostate cancer and a history of either preimplant or postimplant
      transurethral resection of the prostate (TURP) were evaluated. Of the 27
      patients, 1 continued to be catheter dependent and was excluded from analysis. Of
      the remaining 26 patients, each was mailed the urinary function component of the
      Expanded Prostate Cancer Index (EPIC) and the International Prostate Symptom
      Score (IPSS). Twenty-six surveys (100%) were returned. The mean and median follow
      up was 44.8 and 39.8 months, respectively. The clinical, treatment, and
      dosimetric parameters evaluated included age, pretreatment prostate-specific
      antigen level, Gleason score, stage, risk group, prostate volume, presence of
      diabetes and hypertension, tobacco consumption, number of TURPs, number of grams
      resected, ultrasound planning volume, hormonal status, supplemental external beam
      radiotherapy, isotope, follow-up (in months), minimal dose received by 90% of the
      prostate gland, percentage of prostate volume receiving 100%, 150%, and 200% of
      the prescribed minimal peripheral dose, and the average and maximal urethral
      dose. Because baseline IPSSs, but not EPIC scores, were available, a cross
      sectional survey was performed in which 51 newly diagnosed prostate cancer
      patients yet to receive any therapeutic intervention and 195 non-TURP
      brachytherapy patients served as controls. RESULTS: For all evaluated parameters,
      superior urinary scores were noted in the preimplant TURP group, with
      intermediate scores in the postimplant TURP patients and poor urinary QOL scores
      in the pre- and postimplant TURP patients. With time, the EPIC scores improved in
      the pre- and postimplant TURP cohorts. In multivariate linear regression analysis
      of the EPIC urinary summary score, the number of TURPs and supplemental external
      beam radiotherapy were the strongest predictors for diminished QOL. CONCLUSION:
      TURP results in diminished urinary QOL after brachytherapy. However, patients who
      underwent preimplant TURP had urinary QOL approaching that of non-TURP
      brachytherapy patients. Significant urinary dysfunction was noted in
      approximately one-half of patients who underwent postimplant TURP (especially pre
      and postimplant TURP). Because most patients with brachytherapy-related urinary
      obstruction will eventually spontaneously void, TURP should be approached with
      extreme caution and only after substantial time has transpired.

PMID- 14697425
TI  - Evaluation of therapeutic potential of heavy ion therapy for patients with
      locally advanced prostate cancer.
AB  - PURPOSE: To investigate the feasibility of raster scanned heavy charged particle
      therapy in the treatment of prostate cancer (PCa,) with special regard to the
      influence of internal organ motion on the dose distribution. METHODS AND
      MATERIALS: The CT data of 8 patients with PCa who underwent three-dimensional
      conformal radiotherapy (RT) were chosen. In addition to the routine treatment
      planning scan, three to five additional positioning control CT scans were
      performed. The organs at risk and the target volumes were defined on all CT
      scans. Primary and boost carbon ion plans were calculated to deliver 66 Gy to the
      clinical target volume/planning target volume, with an additional 10 Gy to the
      gross tumor volume (GTV). To estimate the influence of internal organ motion on
      plan quality, the dose was recalculated on the basis of the control CT scans. The
      comparative analysis was based on the dose-volume histogram-derived physical
      parameters. RESULTS: The average 90% target coverage was 99.1% for the GTV. The
      maximal dose to the rectum was 71.8 Gy. The average rectal mean dose was 19 Gy.
      The volume of the rectum receiving 70 and 68 Gy was 0.1 and 0.3 cm3. The average
      difference in the 90% coverage for the GTV on control CT cubes was 3.6%. The
      maximal rectal dose increased to 76.2 Gy. The deviation in the mean rectal dose
      was <1 Gy on average. The rectal volume receiving 70 and 68 Gy increased to 2.5
      and 3.3 cm3. CONCLUSION: The investigation demonstrated the feasibility of raster
      scanned carbon ions for PCa RT. Excellent coverage of the target volume and
      optimal sparing of the rectum were acquired. The combination of photon intensity
      modulated RT and a carbon ion boost to the GTV is the most rational solution for
      the gain of clinical experience in heavy ion RT for PCa patients.

PMID- 14697426
TI  - Rectal bleeding and its management after irradiation for uterine cervical cancer.
AB  - PURPOSE: To present an evaluation of the risk factors of radiation-induced rectal
      bleeding and discuss its optimal management in patients with cancer of the
      cervix. METHODS AND MATERIALS: A total of 213 patients treated with radiotherapy
      (RT) alone were included. All patients underwent external beam radiotherapy with
      high-dose-rate brachytherapy. The rectal dose was calculated by both the
      International Commission on Radiation Units and Measurements (ICRU) Report 38
      guidelines and the anterior rectal wall point on radiographs. Rectal bleeding was
      scored using the late effects normal tissue-subjective, objective, management,
      and analytic criteria. RESULTS: The incidence was 12.7% (27 of 213; Grade 1 in 9,
      Grade 2 in 16, and Grade 3 in 2). Most (92.6%) developed rectal bleeding within 2
      years after RT completion (median 16 months). In univariate analysis, three
      significant factors were found: ICRU cumulative rectal biologically equivalent
      dose (CRBED) >100 Gy (19.7% vs. 4.2%), external beam RT dose to the parametrium
      >55 Gy (22.1% vs. 5.1%), and advanced stage (III-IV; 31.8% vs. 10.5%). In
      multivariate analysis, the ICRU-CRBED was the only significant factor. Six
      patients with Grade 1 bleeding experienced immediate relief with sucralfate enema
      for 1 month. For Grade 2 bleeding, sucralfate enema and/or coagulation were
      effective. Grade 3 bleeding lasted for 1 year despite frequent transfusions and
      coagulation. CONCLUSION: Grade 2 and 3 rectal bleeding occurred in 8.5% of
      patients. The most significant risk factor was the ICRU-CRBED. Prompt treatment
      with a combination of sucralfate enema and coagulation was effective in
      controlling Grade 1 and 2 rectal bleeding without the development of fistula or
      stricture.

PMID- 14697427
TI  - High-dose-rate intraoperative radiotherapy for close or positive margins in
      patients with locally advanced or recurrent rectal cancer.
AB  - PURPOSE: A high-dose-rate intraoperative radiotherapy (HDR-IORT) technique for
      rectum cancer was developed and the technique, local failure, and survival were
      analyzed. METHODS AND MATERIALS: After the exclusion of metastatic patients, 37
      patients were treated with external beam RT, surgery, and HDR-IORT between 1997
      and 2000. Primary locally advanced rectum cancer was found in 18 patients and
      recurrent disease in 19. HDR-IORT was only administered if the resection margins
      were < or =2 mm. The flexible intraoperative template is a 5-mm-thick pad with 1
      cm-spaced parallel catheters. Clips were placed during surgery to define the
      target area. A dose of 10 Gy was prescribed at a 1 cm depth from the template
      surface and calculated using standard plans. After treatment, the dose at the
      clips was calculated using the reconstructed template geometry and the actual
      treatment dwell times. The median follow-up of surviving patients was 3 years. No
      patients were lost to follow-up. RESULTS: Overall, 12 patients (32%) had local
      recurrence, 5 (14%) of which were in the HDR-IORT field. The 3-year local failure
      rate for primary tumors and recurrent tumors was 19% and 52%, respectively (p =
      0.0042). The 3-year local failure rate was 37% for negative margins and 26% for
      positive margins (p = 0.51). A high mean dose at the clip (17.3 Gy) was found.
      The overall survival was significantly different for primary vs. recurrent
      tumors, stage, and grade. CONCLUSION: Because of the HDR technique, a high dose
      at the clips was found, with good local control. More out-of-field than in-field
      failures were seen. The local failure rate was significantly different for
      primary vs. recurrent disease.

PMID- 14697428
TI  - Rotterdam and Brussels CT-based neck nodal delineation compared with the surgical
      levels as defined by the American Academy of Otolaryngology-Head and Neck
      Surgery.
AB  - PURPOSE/OBJECTIVE: Rotterdam and Brussels have independently published guidelines
      for the definition and delineation of CT-based neck nodal Levels I-VI. This paper
      first reports on the adequacy of contouring of the Rotterdam delineation
      protocol. Rotterdam and Brussels differed slightly in translating the original
      surgical level definitions as proposed by the 2002 American Academy of
      Otolaryngology-Head and Neck Surgery (AAO-HNS) to CT guidelines. To adapt to the
      surgical level definitions to come to a unifying concept, adjustments of both CT
      based classifications are proposed. METHODS AND MATERIALS: The clinical neck
      nodal target volumes of patients irradiated in Rotterdam by three-dimensional
      conformal radiotherapy (3D-CRT) between December 1998 and March 2001 were
      reviewed. Thirty-four patients with N0 and 27 patients with N+ disease with
      primary tumors located in the oral cavity (n = 1) oropharynx (n = 24),
      hypopharynx (n = 7), and larynx (n = 29) were evaluated. Seven patients underwent
      unilateral (3 N0 patients, 4 N+ patients) and 54 underwent bilateral (31 N0
      patients, 23 N+ patients) irradiation of the neck. In 11 N+ patients, 3D-CRT of
      the neck was followed by unilateral neck dissection. The dose to the primary and
      nonresected N+ necks was 70 Gy and to the N0 neck was 46 Gy. Neck levels were
      analyzed for adequacy of contouring, dose distribution, and patterns of relapse.
      The mean dose and the percentage of the volume receiving a minimum of 95% (V95)
      or >107% (V107) of the prescribed dose was computed. RESULTS: In 4 patients
      treated with bilateral 3D-CRT, contouring was not in concordance with the
      guidelines of the protocol. The V95 and V107 in the 81 adequately contoured N0
      necks (63 irradiated N0 necks from 33 N0 patients, 18 irradiated N0 necks from 24
      N+ patients) was 95.6% and 6.3%, respectively. For the 26 N+ necks (15 N+ necks
      from 13 N+ RT-only patients, 11 N+ necks from 11 preoperatively irradiated
      patients), the V95 and V107 was 94.6% and 6.7%, respectively. With a median
      follow-up of 29 months, in 4 (8.6%) of 46 patients treated by 3D-CRT only,
      regional relapse was found. An actuarial regional and locoregional relapse-free
      survival and disease-free survival rate at 3 years of 90%, 78%, and 68%,
      respectively, was observed. All regional relapses were observed in the N0 necks
      of patients with supraglottic laryngeal carcinoma. Taking the surgical 2002 AAO
      HNS classification as a reference, adjustments are proposed for the Rotterdam and
      Brussels delineation protocols to arrive at a unified CT-based neck nodal
      classification. CONCLUSION: Adequate dose coverage for the Rotterdam CT-based
      contours of the neck nodal levels was found. In the RT-only patients, only four
      failures were observed: one regional and three locoregional relapses. As a next
      step in optimizing the current Rotterdam and Brussels CT-based delineation
      protocols, adaptations are proposed to resolve the discrepancies compared with
      the 2002 AAO-HNS surgical classification.

PMID- 14697429
TI  - Level II lymph nodes and radiation-induced xerostomia.
AB  - PURPOSE: To investigate the influence of the cranial border of electively
      irradiated Level II lymph nodes on xerostomia in patients with oropharyngeal
      cancer using three-dimensional conformal and intensity-modulated radiotherapy (3D
      CRT and IMRT). METHODS AND MATERIALS: The target volumes and organs at risk were
      delineated on the planning CT scans of 12 patients. Two elective target volumes
      were delineated. The first had the transverse process of the C1 atlas and the
      second had the transverse process of the C2 axis as cranial border of the Level
      II lymph nodes. 3D-CRT and IMRT planning were performed for both elective
      volumes, resulting in two plans per patient and technique, called the C1 and C2
      plans, respectively. Irradiation of the ipsilateral elective volume up to C1 and
      the contralateral up to C2 was also performed for IMRT. The normal tissue
      complication probability (NTCP) for xerostomia 1 year after RT was calculated
      using the parotid mean dose. RESULTS: The average mean dose +/- standard
      deviation (SD) to the contralateral parotid gland was reduced from 33 +/- 5 Gy
      for the IMRT C1 plans to 26 +/- 4 Gy for the IMRT C2 plans and from 51 +/- 6 Gy
      to 49 +/- 7 Gy for the 3D-CRT C1 and C2 plans, respectively. The associated NTCP
      +/- SD for xerostomia was 38% +/- 10% for IMRT C1 plans and 24% +/- 6% for IMRT
      up to C2 on the contralateral side, regardless of which cranial border was
      irradiated on the ipsilateral side. For the 3D-CRT C1 and C2 plans, an NTCP value
      of 74% +/- 12% and 71% +/- 15% was obtained, respectively. The NTCP for
      xerostomia of the ipsilateral parotid gland was 53% +/- 17% and 45% +/- 20% for
      the IMRT C1 and C2 plans and 89% +/- 11% and 87% +/- 12% for the 3D-CRT C1 and C2
      plans, respectively. CONCLUSION: Lowering the cranial border of the Level II
      lymph nodes from C1 to C2, in the case of bilateral elective neck irradiation,
      could be considered on the contralateral side when the risk of metastasis on that
      side is very low. This is especially true when IMRT is used, because the relative
      reduction of NTCP for xerostomia 1 year after RT could be up to 68% compared with
      conventional conformal RT up to C1.

PMID- 14697430
TI  - Location of cervical lymph node metastases in oropharyngeal and hypopharyngeal
      carcinoma: implications for cranial border of elective nodal target volumes.
AB  - PURPOSE: To analyze the exact location of the most cranial metastatic cervical
      lymph node in patients with oropharyngeal or hypopharyngeal carcinoma. This was
      done to specify the cranial border of the elective nodal target volume for
      improvement of parotid-sparing irradiation. METHODS AND MATERIALS: The most
      cranial metastatic lymph node, ipsilateral and, when present, contralateral, was
      delineated on 58 diagnostic CT scans of patients with node-positive oropharyngeal
      or hypopharyngeal carcinoma. The distances from the delineated lymph node to the
      base of the skull were measured in all planes. RESULTS: The mean ipsilateral and
      contralateral distance to the base of the skull in the coronal plane was 25.6 mm
      (range 2.6-73.8; SD 14.7) and 34.7 mm (range 10.4-78.9; SD 14.0), respectively (p
      = 0.002). Ipsilateral and contralateral metastatic lymph nodes were located
      within 20 mm below the base of the skull in 24 patients (41%) and 3 patients
      (5%), respectively. CONCLUSION: Contralateral metastatic lymph nodes are more
      caudally located than are ipsilateral metastatic lymph nodes. In elective
      irradiation, lowering the cranial border of the contralateral nodal target volume
      with 20 mm below the base of the skull should be considered.

PMID- 14697431
TI  - Lymph node metastasis of early oral tongue cancer after interstitial
      radiotherapy.
AB  - PURPOSE: To examine the prognostic factors for lymph node metastasis after
      brachytherapy for early (T1-T2N0M0) oral tongue cancer. METHODS AND MATERIALS: We
      reviewed the records of 571 patients (500 low dose rate and 71 high dose rate)
      treated at Osaka University Hospital between 1967 and 1999. RESULTS: Patients
      with lymph node metastasis had tumor with an average diameter of 26 +/- 8 mm and
      a thickness of 9 +/- 5 mm; for patients without lymph node metastasis, the
      corresponding dimensions were 23 +/- 8 mm and 7.5 +/- 4 mm (p = 0.0004 and 0.001,
      respectively). After 5 years, the ulcerative (48%) and indurative/infiltrative
      (39%) types showed a higher ratio of nodal involvement than the exophytic (31%)
      and superficial (19%) types (p <0.0001). Multivariate analysis showed ulceration
      (p = 0.006) and a thickness of <or =6 mm (p = 0.04) to be statistically
      significant predisposing factors for lymph node metastasis. The lymph node
      control rate was 68% in 1967-1979, 71% in 1980-1990, and 66% in 1990-1999; the
      corresponding successful salvage rates for lymph node metastasis were 43%, 33%,
      and 58% (p = 0.04). CONCLUSION: The appearance of the tumor, especially the
      presence or absence of ulceration and the diameter and thickness, are useful
      prognostic indicators for lymph node metastasis. Although the rates of lymph node
      metastasis did not change, the salvage outcome for recurrence after interstitial
      radiotherapy has recently improved.

PMID- 14697432
TI  - Treatment planning comparison of conventional, 3D conformal, and intensity
      modulated photon (IMRT) and proton therapy for paranasal sinus carcinoma.
AB  - PURPOSE: To determine the potential improvements in patients with paranasal sinus
      carcinoma by comparing proton and intensity-modulated radiotherapy (IMRT) with
      conventional and conformal photon treatment planning techniques. METHODS AND
      MATERIALS: In 5 patients, comparative treatment planning was performed by
      comparing proton plans and related conventional, conformal, and IMRT photon
      plans. The evaluations analyzed dose-volume histogram findings of the target
      volumes and organs at risk (OARs, i.e., pituitary gland, optical pathway
      structures, brain, nontarget tissue). RESULTS: The mean and maximal doses, dose
      inhomogeneities, and conformity indexes for the planning target volumes were
      comparable for all techniques. Photon plans resulted in greater volumes of
      irradiated nontarget tissues at the 10-70% dose level compared with the
      corresponding proton plans. The volumes thereby increased by a factor of 1.3-3.1
      for conventional, 1.1-3.8 for conformal, and 1.1-3.7 for IMRT. Compared with
      conventional techniques, conformal and IMRT photon treatment planning options
      similarly reduced the mean dose to the OARs. The use of protons further reduced
      the mean dose to the OARs by up to 65% and 62% compared with the conformal and
      IMRT technique, respectively. CONCLUSION: Compared with conventional treatment
      techniques, conformal RT and IMRT similarly enabled dose reductions to the OARs.
      Additional improvements were obtained using proton-based treatment planning
      modalities.

PMID- 14697433
TI  - Intraoperative high-dose-rate brachytherapy for paranasal sinus tumors.
AB  - PURPOSE: Advanced and recurrent tumors of the paranasal sinuses can be difficult
      to irradiate to high doses with standard external beam radiotherapy (EBRT),
      conventional brachytherapy, or intraoperative electron beams. We, therefore,
      explored the role of intraoperative high-dose-rate brachytherapy (IOHDR) as a
      boost to EBRT in primary tumors or as sole adjuvant treatment in recurrent
      disease. METHODS AND MATERIALS: Between 1992 and 1998, 34 patients with locally
      advanced tumors arising in the paranasal sinuses were treated with IOHDR after
      maximal surgical excision. Twenty-seven patients with new primaries underwent
      gross resection and 10-12.5 Gy IOHDR followed by 45-50 Gy EBRT. Seven previously
      irradiated (45-63 Gy) patients with recurrent disease were treated with 15-20 Gy
      of IOHDR alone after gross excision. Local control and overall survival were
      analyzed using the Kaplan-Meier method and compared using the log-rank test.
      RESULTS: After a mean follow-up of 6 years (range 34-120 months), the 1-, 3-, and
      5-year actuarial survival rate was 80%, 62%, and 44%, respectively. The overall
      local control rate at 1 and 5 years was 75% and 65%, respectively, and distant
      failure was documented in 44% of patients. Subgroup analysis revealed that the
      presence of gross disease after surgical resection was the strongest
      prognosticator, with a 5-year survival and local control rate of 17% and 50%,
      respectively, compared with 60% and 68%, respectively, for microscopic disease.
      The local control rates of patients with new primaries were similar to those of
      patients treated for recurrent disease (63% vs. 71%), probably because gross
      residual disease occurred only in the group of patients with new primaries. The
      addition of EBRT to IOHDR increased the 5-year disease-free survival rate from
      27% to 44% but had no effect on local control (64% vs. 65%). CONCLUSION: IOHDR
      can be safely used to deliver a high radiation dose to locally advanced and
      recurrent tumors in the paranasal sinuses. In an attempt to improve outcome, we
      are now adding limited-dose EBRT (20-30 Gy) after 17.5 Gy of IOHDR in previously
      irradiated patients and increasing the EBRT dose for both microscopic (50-54 Gy)
      and gross residual disease (60-65 Gy) after 15 Gy of IOHDR in previously
      unirradiated patients. Chemosensitization should also be considered in previously
      irradiated patients and in those with gross residual disease. Interstitial
      boosting techniques, which can deliver higher doses at depth, should also be
      considered in patients with gross residual disease.

PMID- 14697434
TI  - Radiotherapy with concomitant weekly docetaxel for Stages III/IV oropharynx
      carcinoma. Results of the 98-02 GORTEC Phase II trial.
AB  - PURPOSE: We designed a prospective Phase II clinical trial to evaluate the
      addition of weekly chemotherapy using Docetaxel during standard radiation therapy
      in patients with Stages III and IV oropharynx carcinoma. METHODS: A total of 63
      patients have been entered in a Phase II multicenter trial. Radiotherapy
      delivered, with conventional fractionation, 70 Gy in 35 fractions. Patients
      received during the period of radiotherapy seven cycles of Docetaxel (20 mg/m2
      each week). RESULTS: Radiotherapy compliance was good in respect to total dose,
      treatment duration, and treatment interruption. The rate of Grade 3 and 4
      mucositis was 84%. Grade 3 and 4 skin toxicity occurred in 53% of the patients.
      Hematologic toxicity was infrequent, with only a 5% rate of Grade 3 or 4
      neutropenia. Three-year overall actuarial survival and disease-free survival
      rates were, respectively, 47% (95% CI = 39-68%) and 39% (95% CI = 30-57%). The
      local and regional control rate was 64%. CONCLUSION: The adjunction of weekly
      Docetaxel to conventional radiotherapy is feasible. Mucositis and skin toxicity
      were the major acute toxic effects. Therapeutic results were similar to those
      observed with concomitant chemotherapy using platinum and/or 5-FU. Further trials
      using Docetaxel in combination with other cytotoxic agents are needed.

PMID- 14697435
TI  - Zinc sulfate in the prevention of radiation-induced oropharyngeal mucositis: a
      prospective, placebo-controlled, randomized study.
AB  - PURPOSE: To determine the effect of oral zinc sulphate supplementation on
      radiation-induced oropharyngeal mucositis in patients with head-and-neck cancer.
      MATERIALS AND METHODS: Thirty patients with head-and-neck cancer were randomly
      assigned to receive either zinc sulfate or placebo. Primary tumors were localized
      in the larynx in 14 patients, in the nasopharynx in 4, in the oral cavity in 4,
      in a salivary gland in 1, in the maxillary sinus in 1, in neck nodes (lymphoma
      presenting primarily) in 3 and in neck metastases from an unknown primary in 3.
      In the placebo group, 3 patients were excluded; 1 patient died during treatment,
      1 left the study, and 1 did not come to the 6 week control visit. The patients
      were treated with telecobalt radiotherapy at conventional fractionation (2
      Gy/fraction, five fractions weekly, for 20-35 fractions within 4-7 weeks). The
      median radiation dose was 6400 cGy (4000-7000 cGy). Oral mucositis was assessed
      by two independent physicians, experts in radiation oncology, using the Radiation
      Therapy Oncology Group Acute Radiation Morbidity Scoring criteria. RESULTS: In
      the zinc sulfate group, Grade 3-4 mucositis was not detected in any patient;
      Grade 0 mucositis was detected in 2, and Grade 1 in 8, and Grade 2 in 5 patients.
      In the placebo group, Grade 2 mucositis was detected in 4 and Grade 3 in 8
      patients. We observed that the degree of mucositis in the patients in the zinc
      sulfate group was significantly lower than that in the placebo group (p < 0.05).
      Confluent mucositis developed earlier in the placebo group than in the zinc
      sulfate group after the onset of treatment (p < 0.05) and started to improve
      sooner in the zinc sulfate group than in the placebo group (p < 0.05).
      CONCLUSIONS: Zinc sulfate is beneficial in decreasing the severity of radiation
      induced mucositis and oral discomfort. These results should be confirmed by
      additional evaluation in randomized studies with a larger number of patients.

PMID- 14697436
TI  - Evaluation of salivary gland function after treatment of head-and-neck tumors
      with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy.
AB  - PURPOSE: To evaluate salivary gland function after inversely planned stereotactic
      intensity-modulated radiotherapy (IMRT) for tumors of the head-and-neck region
      using quantitative pertechnetate scintigraphy. METHODS AND MATERIALS: Since
      January 2000, 18 patients undergoing IMRT for cancer of the head and neck
      underwent pre- and posttherapeutic scintigraphy to examine salivary gland
      function. The mean dose to the primary planning target volume was 61.5 Gy (range
      50.4-73.2), and the median follow-up was 23 months. In all cases, the parotid
      glands were directly adjacent to the planning target volume. The treatment
      planning goal was for at least one parotid gland to receive a mean dose of <26
      Gy. Two quantitative parameters (change in maximal uptake and change in the
      relative excretion rate before and after IMRT) characterizing the change in
      salivary gland function after radiotherapy were determined. These parameters were
      compared with respect to the dose thresholds of 26 and 30 Gy for the mean dose.
      In addition, dose-response curves were calculated. RESULTS: Using IMRT, it was
      possible in 16 patients to reduce the dose for at least one parotid gland to < or
      =26 Gy. In 7 patients, protection of both parotid glands was possible. No
      recurrent disease adjacent to the protected parotid glands was observed. Using
      the Radiation Therapy Oncology Group/European Organization for the Research and
      Treatment of Cancer scoring system, only 3 patients had Grade 2 xerostomia. No
      greater toxicity was seen for the salivary glands. The change in the relative
      excretion rate was significantly greater, if the parotid glands received a mean
      dose of > or =26 Gy or > or =30 Gy. For the change in maximal uptake, a
      statistically significant difference was seen only for the parotid glands and a
      dose threshold of 30 Gy. For the end point of a reduction in the parotid
      excretion rate of >50% and 75%, the dose-response curves yielded a dose at 50%
      complication probability of 34.8 +/- 3.6 and 40.8 +/- 5.3 Gy, respectively.
      CONCLUSION: Using IMRT, it is possible to protect the parotid glands and reduce
      the incidence and severity of xerostomia in patients. Doses <26-30 Gy
      significantly preserve salivary gland function. The results support the
      hypothesis that application of IMRT does not lead to increased local failure
      rates.

PMID- 14697437
TI  - Loss of cervical spinal curvature during radiotherapy for head-and-neck cancers:
      the neck moves, too.
AB  - PURPOSE: We became concerned about our observation of the loss of the normal
      lordotic cervical spinal curvature during the course of radiotherapy (RT) for
      head-and-neck tumors. Our goal was to evaluate formally the cervical lordotic
      curve in 50 random patients by comparing the cervical spinal angles (CSAs)
      measured at the initiation of RT with the CSAs measured during the last week of
      RT. METHODS AND MATERIALS: Fifty patients treated mono-isocentrically for head
      and-neck cancer were selected randomly for review. All patients had custom-made
      masks, shoulder pulls, and multiple tattoos to ensure reproducibility. The CSA
      was defined as the angle formed by the line projected parallel to the posterior
      surface of C2 and the line projected parallel to C6. The measurements were done
      on the simulation film and the first and last port films. RESULTS: The average
      decrease in the CSA was 2.26 degrees (SD +/-2.19 degrees ). In patients with the
      isocenter placed as low as possible, the change was significantly more compared
      with the remaining population. (3.8 degrees vs. 1.7 degrees, p = 0.004).
      CONCLUSION: Despite customized immobilization, the neck position changes during
      the course of RT for head-and-neck tumors. Patients with the isocenter placed
      very low have the least long-term reproducibility and a comfortable position may
      be best suited to intensity-modulated RT for such head-and-neck cancer patients.

PMID- 14697438
TI  - Nasopharyngeal carcinoma in children: ten years' experience at the Tata Memorial
      Hospital, Mumbai.
AB  - PURPOSE: To evaluate the disease characteristics and outcome of children with
      nasopharyngeal carcinoma treated at the Tata Memorial Hospital, Mumbai. METHODS
      AND MATERIALS: Between 1990 and 2000, 81 pediatric patients with a diagnosis of
      nasopharyngeal carcinoma were treated at the Tata Memorial Hospital. The median
      age was 14 years. The male/female ratio was 2.8:1. Of the 81 patients, 32 (39%),
      21 (26%), and 28 (35%) had T1-T2, T3, and T4 (TNM International Union Against
      Cancer staging system, 1997), respectively. Ninety-one percent presented with
      nodal metastasis. Thirty patients (37%) had lymph nodes >6 cm, and 45 (56%) had
      bilateral nodes at presentation. Histologically, 77 patients (95%) had
      undifferentiated carcinoma. Eighty-five percent received neoadjuvant multiagent
      chemotherapy containing bleomycin, methotrexate, and cisplatin, followed by
      radiotherapy (RT). RESULTS: After a median follow-up of 50 months, the disease
      free survival (DFS) and overall survival (OS) rate for the entire group was 45%
      and 54%, respectively. Kaplan-Meier curves were used for evaluation of prognostic
      factors and were compared using the log-rank test. Nodal status had a significant
      impact on DFS (p = 0.021) and OS (p = 0.006). Complete responders to chemotherapy
      had superior DFS (p = 0.000) and OS (p = 0.000). RT doses >60 Gy resulted in
      better DFS (p = 0.020) and OS (p = 0.012). Combined chemotherapy plus RT resulted
      in improved DFS (p = 0.457) and OS (p = 0.296), although the difference was not
      statistically significant. CONCLUSION: Combined modality management using
      chemotherapy and RT resulted in satisfactory locoregional control and OS in
      pediatric patients with nasopharyngeal carcinoma. Nodal involvement, response to
      chemotherapy, and RT dose were important prognostic factors.

PMID- 14697439
TI  - Comparison of the efficacy and acute toxicity of weekly versus daily
      chemoradiotherapy for non-small-cell lung cancer: a meta-analysis.
AB  - PURPOSE: Recent studies have reported improved survival with concurrent
      chemoradiotherapy (ChRT) for inoperable non-small-cell lung cancer (NSCLC). ChRT
      includes the delivery of low-dose chemotherapy given daily during radiotherapy
      (RT) or higher doses administered weekly. It remains unknown whether a difference
      in efficacy or toxicity exists between these approaches. A systematic review was
      performed to compare the efficacy and toxicity of weekly vs. daily ChRT. METHODS
      AND MATERIALS: The results from randomized studies comparing ChRT to RT for NSCLC
      were pooled using meta-analyses. The relative risk (RR) of death at 1, 2, and 3
      years and of acute esophagitis, pneumonitis, or neutropenia (World Health
      Organization Grade 3 or greater) were determined. RESULTS: Ten studies involving
      1802 patients were included. No significant difference in mortality or toxicity
      was observed between the weekly and daily regimens: RR of death at 2 years-weekly
      0.93, 95% confidence interval [CI] 0.87-0.99; daily 0.92, 95% CI 0.85-1.00; RR of
      death at 3 years-weekly 0.93, 95% CI 0.89-0.98; daily 0.90, 95% CI 0.81-1.01; RR
      of esophagitis-weekly 2.07, 95% CI 0.96-4.46; daily 1.70, 95% CI 1.17-2.48; RR of
      pneumonitis-weekly 1.52, 95% CI 0.93-2.48; daily 1.17, 95% CI 0.65-2.09; and RR
      of neutropenia-weekly 8.57, 95% CI 3.75-19.58; daily 11.93, 95% CI 1.55-92.12.
      CONCLUSION: No statistically significant difference in efficacy or acute toxicity
      was observed to suggest the superiority of daily vs. weekly ChRT regimens for
      NSCLC.

PMID- 14697440
TI  - Equivalent outcome of patients with clinical Stage IIIA non-small-cell lung
      cancer treated with concurrent chemoradiation compared with induction
      chemotherapy followed by surgical resection.
AB  - PURPOSE: To compare the outcome of induction chemotherapy followed by surgery
      (C/S) and concurrent chemoradiotherapy (CRT) for clinical Stage IIIA non-small
      cell lung cancer (NSCLC). METHODS AND MATERIALS: Between 1990 and 2000, 107
      patients underwent either induction C/S (n = 55) or concurrent CRT (n = 52) for
      clinical Stage IIIA NSCLC at The University of Texas M. D. Anderson Cancer
      Center. Patient and tumor characteristics were balanced in the two treatment
      groups with respect to T and N stage, race, median age, performance status,
      weight loss, and histologic findings. In the C/S group, induction chemotherapy
      included two to four cycles of cisplatin-based chemotherapy followed by lobectomy
      and mediastinal lymph node dissection. Postoperative RT was delivered in 35
      patients, with referral for RT made at the discretion of the treating physician.
      CRT consisted of three cycles of cisplatin-based chemotherapy given every 3 weeks
      concurrent with RT to 60-63 Gy in 30-35 fractions in 27 patients and 69.6 Gy in
      58 fractions (b.i.d.) in 25 patients. Local control, overall disease-free
      survival, and distant metastasis-free survival rates were calculated using the
      Kaplan-Meier method. The median follow-up duration was 20 months in all patients
      and 32 months in surviving patients. RESULTS: No statistically significant
      differences were found in the end points measured in the two treatment groups.
      Specifically, the median survival time was 31 and 27 months and the 5-year
      overall survival rate was 33% and 30% in the C/S and CRT groups, respectively.
      Likewise, the 5-year local control (58% vs. 61%), disease-free (24% vs. 23%), and
      distant metastasis-free (44% vs. 36%) survival rates in the two groups were not
      significantly different. In the C/S group, postoperative RT significantly
      improved the 5-year local control rate from 33.8% to 81.5% (p = 0.007) but did
      not significantly improve overall survival. Additionally, patients in the C/S
      group whose disease responded to induction chemotherapy had a significantly
      improved 5-year overall survival rate (50%) compared with those who had stable or
      progressive disease (16%, p = 0001). CONCLUSION: Treatment of Stage IIIA NSCLC
      using either induction C/S or CRT resulted in similar outcomes in terms of local
      control and median overall, 5-year overall, distant metastasis-free, and disease
      free survival. However, patients undergoing induction C/S often needed
      postoperative RT to achieve local control equivalent to that achieved with
      concurrent CRT. Advances in radiation-based treatment as reflected in this study
      have resulted in similar outcomes compared with modern induction C/S. To improve
      survival, however, newer systemic agents that reduce and control distant
      metastasis are required.

PMID- 14697441
TI  - Pentoxifylline in prevention of radiation-induced lung toxicity in patients with
      breast and lung cancer: a double-blind randomized trial.
AB  - PURPOSE: Pentoxifylline (Ptx) is thought to be helpful in preventing
      radiotoxicity by inhibiting platelet aggregation and tumor necrosis factor. We
      assessed whether prophylactic use of Ptx could prevent early and late normal lung
      tissue damage due to radiotherapy in a double-blind, randomized trial. METHODS
      AND MATERIALS: A total of 40 patients with lung or breast cancer were randomized
      to receive Ptx (400 mg) or a placebo, 3 times daily, during the entire period of
      radiotherapy. We used the late effects normal tissue-subjective, objective,
      management, and analytic (LENT-SOMA) scale to evaluate and compare toxicity,
      including the findings of pulmonary function tests and radiologic and
      scintigraphic evaluations performed before and at 3 and 6 months of follow-up.
      RESULTS: According to the LENT score, a statistically significant difference was
      found between the two groups in favor of Ptx (p = 0.016). The difference in
      diffusing capacity of the lung for carbon monoxide and regional perfusion scan
      results were found to be statistically significant between the groups at 3 and 6
      months (p <0.05). The use of Ptx resulted in a noticeable reduction in the higher
      degrees of lung injury detected radiologically. CONCLUSION: Our study showed a
      significant protective effect of Ptx for both early and late lung radiotoxicity.
      We recommend the prophylactic use of Ptx, finding it to be safe and effective.

PMID- 14697442
TI  - Optimization of MammoSite therapy.
AB  - PURPOSE: Radiation source anisotropy causes about 10% of a spherically shaped
      planning target volume surrounding a MammoSite balloon to receive less than the
      prescribed dose. The principal dose-limiting factor for MammoSite therapy is the
      dose to the overlying skin. Additional limiting factors potentially include the
      dose to portions of the heart and lung. The goal of optimization is to deliver
      the prescribed dose to as much of the planning target volume as possible while
      avoiding toxicity to adjacent organs. METHODS AND MATERIALS: An experimental CT
      based high-dose-rate brachytherapy treatment planning system was used to
      investigate optimization strategies for MammoSite treatment. This system
      implements a linear optimization of high-dose-rate dwell times on the basis of
      constraints assigned to points of interest and a set of potential dwell
      positions. RESULTS: The cylindrical symmetry of the MammoSite catheter limits the
      optimization process to creating spherical, ellipsoidal, or egg-shaped isodose
      distributions whose major axis is oriented along the catheter axis. If the dose
      to a limiting structure, such as skin, is not an issue, the use of multiple dwell
      positions can compensate for source anisotropy and create a more spherical
      isodose surface enclosing the planning target volume compared with a single dwell
      position. When skin becomes a dose-limiting factor, the catheter axis
      orientation, source anisotropy, dwell position, and dwell weighting can be
      exploited to limit the skin dose while simultaneously preserving the prescribed
      dose to as much of the target volume as possible. CONCLUSION: Optimization of
      MammoSite therapy using multiple dwell positions within the balloon is both
      possible and practical.

PMID- 14697443
TI  - Fifteen-year results of breast-conserving surgery and definitive irradiation for
      Stage I and II breast carcinoma: the University of Pennsylvania experience.
AB  - PURPOSE: To determine the 15-year outcomes for women with early stage breast
      cancer after breast conservation therapy. METHODS AND MATERIALS: Between 1977 and
      1990, 937 women with Stage I and II breast carcinoma (55% T1N0, 16% T2N0, 18%
      T1N1, and 11% T2N1) underwent lumpectomy, axillary lymphadenectomy, and
      definitive irradiation. The median patient age was 52 years. Of the 937 patients,
      375 (40%) received adjuvant chemotherapy and/or hormonal therapy, including 249
      (92%) of the 270 women with pathologically positive nodes. The median follow-up
      was 10.1 years. RESULTS: For the overall group, the 15-year overall survival rate
      was 71%, and the rate of freedom from distant metastases was 76%. The 15-year
      local failure rate was 19%. The 15-year contralateral breast cancer rate was 12%.
      The most common first events were distant failure (13%), local failure (10%),
      contralateral breast cancer (7%), and second malignant neoplasms (6%). The local
      failure rate at 10 years for favorable subsets of tumors characterized by
      mammographic detection, resection with negative margins, treatment with
      chemotherapy, and treatment with hormones was 8%, 10%, 10%, and 7%, respectively.
      Local failures were most commonly observed within (true recurrence), or just
      outside (marginal miss), the primary tumor bed (66%, 85 of 128). The rate of true
      recurrence or marginal miss at 5, 10, and 15 years was 5%, 10%, and 12%,
      respectively. CONCLUSION: These high rates of survival and local control confirm
      that breast conservation therapy yields favorable results in women with early
      breast cancer into the second decade after treatment.

PMID- 14697444
TI  - Randomized, paired comparison of No-Sting Barrier Film versus sorbolene cream
      (10% glycerine) skin care during postmastectomy irradiation.
AB  - PURPOSE: Postmastectomy irradiation provides an excellent model for irradiated
      skin care practices because of the relatively uniform surface and radiation
      compared with other situations in which radiation-induced moist desquamation is
      common. We designed a study to test the effect of prophylactic 3M Cavilon No
      Sting Barrier Film (No-Sting) on the rates of moist desquamation compared with
      sorbolene cream (with 10% glycerin). METHODS AND MATERIALS: The irradiated chest
      wall was divided into medial and lateral halves. Sixty-one women were randomized
      to have No-Sting applied to either the medial or lateral half, with the alternate
      half treated with sorbolene. RESULTS: For all patients, the skin toxicity,
      calculated as the area under the curve, mean No-Sting and sorbolene score was 8.1
      vs. 9.2, respectively (p = 0.005, Wilcoxon signed rank test). The total number of
      weeks of moist desquamation for the 61 patients was 40 vs. 45, equating to a mean
      of 0.65 week vs. 0.74 week per patient in the No-Sting and sorbolene-treated
      areas, respectively. The rates of moist desquamation were 33% vs. 46% (p = 0.096,
      McNemar's Exact test). For 58 fully assessable patients (minimum of 7 weekly
      observations), the area under the curve and rates of moist desquamation were
      significantly different statistically (p = 0.002 and 0.049, respectively). No
      statistically significant differences were noted in the pain scores. The pruritus
      scores were significantly reduced in the No-Sting area (area under the curve, p =
      0.011). CONCLUSION: No-Sting reduces the duration and frequency of radiation
      induced moist desquamation.

PMID- 14697445
TI  - The use of hypofractionated intensity-modulated irradiation in the treatment of
      glioblastoma multiforme: preliminary results of a prospective trial.
AB  - PURPOSE: Despite major advances in treatment modalities, the prognosis of
      patients with glioblastoma multiforme (GBM) remains poor. Exploring
      hypofractionated regimens to replace the standard 6-week radiotherapy schedule is
      an attractive strategy as an attempt to prevent accelerated tumor cell
      repopulation. There is equally interest in dose escalation to the gross tumor
      volume where the majority of failures occur. We report our preliminary results
      using hypofractionated intensity-modulated accelerated radiotherapy regimen in
      the treatment of patients with GBM. METHODS AND MATERIALS: Between July 1998 and
      December 2001, 25 patients with histologically proven diagnosis of GBM, Karnofsky
      performance status > or =60, and a postoperative tumor volume < or =110 cm3 were
      treated with a hypofractionated accelerated course of radiotherapy. The gross
      tumor volume (GTV) was defined as the contrast-enhancing lesion on the
      postoperative MRI T1-weighted images with the latter fused with computed
      tomography images for treatment planning. The planning target volume was defined
      as GTV + 1.5-cm margin. Using forward-planning intensity modulation (step-and
      shoot technique), 60 Gy in 20 daily fractions of 3 Gy each were given to the GTV,
      whereas the planning target volume received a minimum of 40 Gy in 20 fractions of
      2 Gy each at its periphery. Treatments were delivered over a 4-week period using
      5 daily fractions per week. Dose was prescribed at the isocenter (ICRU point).
      Three beam angles were used in all of the cases. RESULTS: Treatments were well
      tolerated. Acute toxicity was limited to increased brain edema during
      radiotherapy in 2 patients who were on tapering doses of corticosteroids. This
      was corrected by increasing the steroid dose. At a median follow-up of 8.8
      months, no late toxicity was observed. One patient experienced visual loss at 9
      months after completion of treatment. MRI suggested nonspecific changes to the
      optic chiasm. On review of the treatment plan, the total dose to the optic chiasm
      was confirmed to be equal to or less than 40 Gy in 20 fractions. When Radiation
      Therapy Oncology Group recursive partitioning analysis was used, 10 patients were
      class III-IV, and 15 patients were class V-VI. To date, 21 patients have had
      clinical and/or radiologic evidence of disease progression, and 16 patients have
      died. The median survival was 9.5 months (range: 2.8-22.9 months), the 1-year
      survival rate was 40%, and the median progression-free survival was 5.2 months
      (range: 1.9-12.8 months). CONCLUSION: This hypofractionated accelerated
      irradiation schedule using forward planning (step-and-shoot) hypofractionated,
      intensity-modulated accelerated radiotherapy is feasible and seems to be a safe
      treatment for patients with GBM. A 2-week reduction in the treatment time may be
      of valuable benefit for this group of patients. However, despite this accelerated
      regimen, no survival advantage has been observed.

PMID- 14697446
TI  - Results of whole brain radiotherapy and recursive partitioning analysis in
      patients with brain metastases from renal cell carcinoma: a retrospective study.
AB  - PURPOSE: To determine the benefit of whole brain radiotherapy (WBRT) and the use
      of the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis
      (RPA) classification system in patients with brain metastases from renal cell
      carcinoma. METHODS AND MATERIALS: We identified 46 consecutive patients with
      brain metastases from renal cell carcinoma who were treated with WBRT at the
      Cleveland Clinic Foundation between 1983 and 2000. We reviewed their charts for
      patient and tumor characteristics and categorized them according to the RTOG RPA
      classes. RESULTS: The median follow-up and survival time for all 46 patients (15
      women and 31 men) was 3.0 months. The median radiation dose was 3000 cGy in 10
      fractions. Patients who received higher radiation doses (>3000 cGy) survived
      longer than those who received 3000 cGy or less than 3000 cGy (8.5 months vs. 2.7
      months vs. 0.4 months, p = 0.0289). However, the Karnofsky performance status and
      RPA class were confounding factors in these data. The median survival for
      patients by RTOG RPA class was 8.5 months for Class I (n = 2), 3 months for Class
      II (n = 37), and 0.6 months for Class III (n = 7, p = 0.0834). CONCLUSION:
      Despite the relatively poor prognosis of patients who receive WBRT alone, it
      appears that they benefit from this palliative treatment. The RTOG RPA
      classification system may be a useful tool in assessing prognosis in this patient
      population.

PMID- 14697447
TI  - Late neointimal tissue growth behind the stent after intravascular gamma
      radiation.
AB  - PURPOSE: To determine the nature of the changes of the vascular wall after
      intravascular brachytherapy in stented arteries leading to incomplete stent
      apposition. METHODS AND MATERIALS: Stents were implanted in the infrarenal aortas
      of rabbits, and gamma-intravascular brachytherapy (18 Gy) or a sham radiation
      procedure was immediately implemented. The arteries were harvested at 6 months
      for histologic analyses. RESULTS: The external elastic lamina area, as well as
      the vascular wall area behind the stent, were significantly greater in irradiated
      vs. control arteries (8.94 +/- 0.68 mm2 vs. 6.87 +/- 0.40 mm2 [p <0.001] and 1.56
      +/- 0.13 mm2 vs. 0.72 +/- 0.07 mm2 [p <0.001], respectively). The ratio of the
      intimal area behind the stent related to the total intimal area was greater in
      the irradiated segments (control vs. irradiated: 9.0% +/- 5.9% vs. 55.3% +/-
      15.5%, p <0.05). Neointimal growth of the irradiated vessels outside the stent
      was characterized by marked fibrin depositions and an inflammatory response
      around the stent struts. CONCLUSION: Our study revealed the presence of a
      neointimal layer specifically located behind the stent, which represented the
      result of an unhealed fibrin-rich tissue growth process 6 months after
      intravascular brachytherapy.

PMID- 14697448
TI  - Combination of boron neutron capture therapy and external beam radiotherapy for
      brain tumors.
AB  - PURPOSE: Boron neutron capture therapy (BNCT) has been used clinically as a
      single modality treatment for high-grade gliomas and melanomas metastatic to the
      brain. The purpose of the present study was to determine whether its efficacy
      could be enhanced by an X-ray boost administered after BNCT. Two brain tumor
      models were used, the F98 glioma as a model for primary brain tumors and the MRA
      27 human melanoma as a model for metastatic brain tumors. METHODS AND MATERIALS:
      For biodistribution studies, either 10(5) F98 glioma cells were implanted
      stereotactically into the brains of syngeneic Fischer rats or 10(6) MRA 27
      melanoma cells were implanted intracerebrally into National Institutes of Health
      (NIH)-rnu nude rats. Biodistribution studies were performed 11-13 days after
      implantation of the F98 glioma and 20-24 days after implantation of the MRA 27
      melanoma. Animals bearing the F98 glioma received a combination of two boron
      containing drugs, sodium borocaptate at a dose of 30 mg/kg and boron
      phenylalanine (BPA) at a dose of 250 mg/kg. MRA 27 melanoma-bearing rats received
      BPA (500 mg/kg) containing an equivalent amount of 10B (27 mg B/kg). The drugs
      were administered by either intracarotid or i.v. injection. RESULTS: The tumor
      boron concentration after intracarotid injection was approximately 50% greater in
      the F98 glioma and MRA 27 melanoma after intracarotid injection (20.8 and 36.8
      microg/g, respectively) compared with i.v. injection (11.2 and 19.5 microg/g,
      respectively). BNCT was carried out at the Brookhaven National Laboratory Medical
      Research Reactor approximately 14 days after tumor implantation of either the F98
      glioma or the MRA 27 melanoma. Approximately 7-10 days after BNCT, subsets of
      animals were irradiated with 6-MV photons, produced by a linear accelerator at a
      total dose of 15 Gy, delivered in 5-Gy daily fractions. F98 glioma-bearing rats
      that received intracarotid or i.v. sodium borocaptate plus BPA, followed 2.5 h
      later by BNCT and 7-10 days later by X-rays, had similar mean survival times (61
      days and 53 days, respectively, p = 0.25), and the non X-irradiated, BNCT-treated
      animals had a mean survival time of 52 and 40 days, respectively, for
      intracarotid vs. i.v. injection; the latter was equivalent to that of the
      irradiated animals. The corresponding survival time for MRA 27 melanoma-bearing
      rats that received intracarotid or i.v. BPA, followed by BNCT and then X
      irradiation, was 75 and 82 days, respectively (p = 0.5), 54 days without X
      irradiation (p = 0.0002), 37 days for X-irradiation alone, and 24 days for
      untreated controls. In contrast to the data obtained with the F98 glioma, MRA 27
      melanoma-bearing rats that received i.v. BPA, followed by BNCT, had a highly
      significant difference in mean survival time compared with the irradiated
      controls (54 vs. 37 days, p = 0.008). CONCLUSION: Our data are the first to
      suggest that a significant therapeutic gain may be obtained when BNCT is combined
      with an X-ray boost. Additional experimental studies are required to determine
      the optimal combination of X-radiation and neutron doses and whether it is more
      advantageous to administer the photon boost before or after BNCT.

PMID- 14697449
TI  - A biplane angiographic study on cardiac motion of coronary artery stents: options
      to minimize the target volume for high-precision external beam radiotherapy of
      coronary artery in-stent restenosis.
AB  - PURPOSE: High-precision external beam radiotherapy (EBRT) has been suggested as a
      potential alternative to endovascular brachytherapy for the treatment of coronary
      artery in-stent restenosis. The purpose of our study was to investigate and
      compare different options to define a smallest feasible target volume. METHODS
      AND MATERIALS: The cardiac motion of 17 coronary artery stents in 17 patients was
      studied by use of biplane conventional angiography, recorded during breath-hold.
      Each stent was reconstructed in three dimensions by use of biplane sets of frames
      covering an entire cardiac cycle. The volume traversed by the stent during the
      entire or part of the cardiac cycle was determined. Four options to define the
      stent-traversed volume (STV) as a target for high-precision EBRT were
      investigated. RESULTS: The mean STV during the entire cardiac cycle was 3.5 cm3;
      the STV represented less than 1% of the heart volume in all patients. The STV
      during the diastolic and systolic phase resulted in a mean reduction of 26.6% and
      29.1%, respectively, compared with the STV during the entire cardiac cycle. The
      smallest STV, measured during a 160-ms interval within the cardiac cycle,
      resulted in a mean maximal reduction of 75.9% compared with the STV during the
      entire cardiac cycle. CONCLUSIONS: The STV during the entire cardiac cycle
      represents a small potential target volume for high-precision EBRT. A significant
      reduction of this target volume is possible in case of definition during a
      selected interval within the cardiac cycle.

PMID- 14697450
TI  - A modified relocatable stereotactic frame for irradiation of eye melanoma: design
      and evaluation of treatment accuracy.
AB  - PURPOSE: To describe a reliable, patient-friendly relocatable stereotactic frame
      for irradiation of eye melanoma and to evaluate the repositioning accuracy of the
      stereotactic treatment. METHODS AND MATERIALS: An extra construction with a
      blinking light and a camera is attached to a noninvasive relocatable Gill-Thomas
      Cosman stereotactic frame. The position of the blinking light is in front of the
      unaffected eye and can be adjusted to achieve an optimal position for
      irradiation. The position of the diseased eye is monitored with a small camera. A
      planning CT scan is performed with the affected eye in treatment position and is
      matched with an MR scan to improve the accuracy of the delineation of the tumor.
      Both the translation and rotation of the affected eye are calculated by comparing
      the planning CT scan with a control CT scan, performed after the radiation
      therapy is completed. RESULTS: Nineteen irradiated eye melanoma patients were
      analyzed. All patients received 5 fractions of 10 Gy within 5 days. The depth
      confirmation helmet measurements of the day-to-day treatment position of the
      skull within the Gill-Thomas-Cosman frame were analyzed in the anteroposterior,
      lateral, and vertical directions and were 0.1 +/- 0.3, 0.0 +/- 0.2, and 0.2 +/-
      0.2 mm (mean +/- SD), respectively. The average translations of the eye on the
      planning and control CT scan were 0.1 +/- 0.3 mm, 0.1 +/- 0.4, and 0.1 +/- 0.5
      mm, respectively. The median rotation of the diseased eye was 8.3 degrees.
      CONCLUSIONS: The described Rotterdam eye fixation system turned out to be a
      feasible, reliable, and patient-friendly system.

PMID- 14697451
TI  - Influence of prostate volume on dosimetry results in real-time 125I seed
      implantation.
AB  - PURPOSE: Achieving a minimal dose of 140 Gy to 90% of the prostate (D90) on
      postimplant dosimetry has been shown to yield improved biochemical control by
      125I brachytherapy, and a D90 >180 Gy can be associated with increased long-term
      toxicity of seed implantation. Significant enlargement of the prostate on
      postimplant CT compared with the ultrasound (US) volume at implantation (CT/US
      ratio) has been associated with lower dose results, but other factors predicting
      for high or low doses are not well established. We determined whether the
      prostate size at implantation influenced the CT/US ratio results affecting
      postimplant dosimetry or predicted for D90 values <140 or >180 Gy in patients
      implanted with 125I in a community hospital setting. METHODS AND MATERIALS: The
      dosimetry results from 501 patients from 33 community hospitals were analyzed
      after full dose 125I implantation. Implant radioactivity was obtained from
      reference tables relating millicuries to prostate volume (PV). Seeds were placed
      under real-time US guidance with peripheral weighting in a uniform method for all
      prostate sizes. CT-based dosimetry was performed 1 month after implantation. Dose
      volume histogram parameters were analyzed for volume effects, including D90, the
      dose to 10% and 30% of the rectal wall, and the dose to 30% of the urethra and
      bladder. The PV was defined as small (<25 cm3), medium (25 to <40 cm3), or large
      (> or =40 cm3). RESULTS: The PV ranged from 9 to 79 cm3 (median 32.7). A D90 > or
      =140 Gy was achieved in 452 patients (90%). The median D90 was 164 Gy (range 90
      230) and increased from 149.5 Gy in small prostates to 164 Gy in medium (p
      <0.001) and 176 Gy in large (p <0.001) prostates. A D90 <140 Gy occurred in 20%
      of small vs. 9% of medium and 3% of large prostates (p = 0.003). A D90 >180 Gy
      occurred in 7% of small and 10% of medium vs. 25% of large glands (p <0.001). The
      rectal dose increased significantly with an enlarging PV. The bladder and
      urethral doses increased from the small to medium PVs, although did not increase
      further in the large glands. The median CT/US ratios showed a significant volume
      relationship, decreasing with enlarging PVs, but were not associated with a D90
      <140 or >140 Gy. The D90 results for <140 Gy and >140 Gy occurred at equal
      activities per volume. CONCLUSION: Ninety percent of patients implanted by
      community-level practitioners using reference tables and real-time US-guided
      implantation achieved a D90 outcome of > or =140 Gy. Significant differences in
      dose outcomes <140 Gy and >180 Gy occurred related to PV. Those with prostates
      <25 cm3 had a 20% frequency of D90 <140 Gy, unrelated to excessive postimplant
      volume enlargement or insufficient activity per reference table, suggesting that
      the activity-to-volume recommendations may not allow for much variance in final
      seed position. Such seed displacement may contribute to lower doses, most
      commonly in small glands. One may consider increasing the activity implanted in
      small prostates, because a D90 >180 Gy occurred in only 7% of these cases.
      Patients with glands >40 cm3 were 25% likely to have a D90 result >180 Gy and
      were at only 3% risk of a D90 <140 Gy. These patients may benefit from
      intraoperative dosimetry or a reduction in implant activity.

PMID- 14697452
TI  - Streptokinase--a clinically useful thrombolytic agent.
AB  - A failure of hemostasis and consequent formation of blood clots in the
      circulatory system can produce severe outcomes such as stroke and myocardial
      infraction. Pathological development of blood clots requires clinical
      intervention with fibrinolytic agents such as urokinase, tissue plasminogen
      activator and streptokinase. This review deals with streptokinase as a clinically
      important and cost-effective plasminogen activator. The aspects discussed
      include: the mode of action; the structure and structure-function relationships;
      the structural modifications for improving functionality; recombinant
      streptokinase; microbial production; and recovery of this protein from crude
      broths.

PMID- 14697456
TI  - Circadian variation of plaque rupture in acute myocardial infarction.
AB  - Studies have reported a circadian variation in the onset of acute myocardial
      infarction (AMI). Pathologic studies have revealed that plaque rupture is 1 of
      the major causes of AMI, but none of these has looked specifically at the
      circadian variation of plaque rupture. The aim of this study was to use
      intravascular ultrasound (IVUS) to investigate the circadian variation of plaque
      rupture in AMI. This study included 174 consecutive patients with AMI who
      underwent preinterventional IVUS. All patients were assigned to either a rupture
      group or a nonrupture group according to the preinterventional IVUS. In the 81
      patients (47%) in the rupture group, the frequency of the onset of AMI increased
      significantly in the period from 6 A.M. to 12 P.M. compared with all other time
      periods (p <0.05). The clinical features of AMI in the rupture group were
      characterized as occurring significantly more at rest (67% vs 31%, p <0.01) and
      after significantly less preinfarction angina (22% vs 57%, p <0.01) compared with
      the nonrupture group. A different circadian variation was identified in the
      nonrupture group, characterized as a significant nocturnal nadir (12 to 6 A.M.
      compared with all other periods, p <0.05). The circadian variation of AMI is the
      result of a morning increase in incidence of plaque rupture.

PMID- 14697457
TI  - Increased coronary arterial release of interleukin-1 receptor antagonist and
      soluble CD40 ligand indicative of inflammation associated with culprit coronary
      plaques.
AB  - Blood taken from the coronary artery ostium reflects biochemical changes
      indicative of thrombosis in the culprit vessel. We sought to determine whether
      inflammation is manifested by increased concentrations of selected markers in
      ostial blood sampled from a culprit coronary artery proximal to an
      atherosclerotic plaque. The concentrations of C-reactive protein (CRP),
      interleukin (IL)-6, IL-1 receptor antagonist, and soluble CD40 ligand (sCD40L)
      were measured in blood drawn from 75 patients before percutaneous coronary
      intervention from the femoral artery and from a guide catheter after engagement
      of the culprit coronary artery. Results were compared using Student's t tests. An
      acute coronary syndrome was present in 88% of patients. The concentrations of CRP
      and IL-6 were similar in coronary ostial and peripheral blood. Concentrations of
      IL-1 receptor antagonist were consistently greater in coronary arterial compared
      with peripheral arterial blood (peripheral 545 +/- 378 vs coronary 595 +/- 388
      pg/ml, p = 0.003). Concentrations of sCD40L were also greater in the coronary
      compared with peripheral blood (peripheral 0.80 +/- 0.46 vs coronary 2.12 +/-
      2.77 ng/ml, p <0.0001). The increased concentration of IL-1 receptor antagonist
      and sCD40L in blood drawn from the culprit coronary artery compared with that
      taken from the peripheral artery suggests that these cytokines contribute
      directly to inflammation in response to coronary intervention and may potentiate
      a systemic inflammatory state.

PMID- 14697458
TI  - Usefulness of attenuated heart rate recovery immediately after exercise to
      predict endothelial dysfunction in patients with suspected coronary artery
      disease.
AB  - Attenuated heart rate recovery after graded exercise, which is associated with
      decreased vagal activity, is a powerful predictor of overall mortality.
      Endothelial function plays a key role in determining the clinical manifestations
      of established atherosclerotic lesions and has shown to be suppressed by
      increased sympathetic tone. We designed this study to determine whether patients
      with an attenuated heart rate recovery after exercise could predict endothelium
      dysfunction. Sixty-six patients with suspected coronary artery disease were
      enrolled, and a noninvasive method of brachial ultrasound was used to measure
      endothelium-dependent flow-mediated vasodilation and endothelium-independent
      nitroglycerin-mediated vasodilation. The patients were divided equally into 3
      groups according to heart rate recovery in 1 minute after peak exercise (n = 22
      in each group): group 1 had heart rate recovery of </=19 beats in the first
      minute; group 2, 20 to 28 beats; and group 3 had >/=29 beats. The endothelium
      dependent flow-mediated vasodilation responses were significantly decreased in
      group 1 compared with groups 2 and 3 (2.5 +/- 3.0 vs 5.0 +/- 3.4 vs 5.4 +/- 2.7%,
      p = 0.006), but responses to sublingual nitroglycerin showed no difference among
      the 3 groups (p = 0.332). According to multivariate analysis, heart rate recovery
      after exercise was an independent predictor of endothelial function.

PMID- 14697459
TI  - Incidence of recovery of contractile function following revascularization in
      patients with ischemic left ventricular dysfunction.
AB  - Contractile function in patients with ischemic left ventricular (LV) dysfunction
      may improve after myocardial revascularization. Currently, the incidence of
      contractile function recovery after revascularization in these patients is
      unclear. The aim of this study was to assess the incidence of function
      improvement after myocardial revascularization in patients with ischemic LV
      dysfunction. A total of 258 consecutive patients (aged 59 +/- 12 years) with
      severely depressed LV ejection fractions (EFs) due to chronic coronary artery
      disease and heart failure symptoms were studied. All patients underwent
      radionuclide ventriculography and 2-dimensional echocardiography at rest before
      and 3 to 6 months after revascularization. At baseline, 1,330 segments (32%) were
      normal and 2,775 segments (68%) were dysfunctional. Improvement after
      revascularization occurred in 736 of the 2,775 dysfunctional segments (27%).
      Overall, LVEF improved from 29 +/- 7 to 32 +/- 9 (p <0.0001). A clinically
      significant improvement of LVEF (>/=5% postrevascularization) was present in 101
      patients (39%). Improvement of LVEF after revascularization was frequently
      observed in patients with a more severely impaired baseline LVEF. At least 3
      segments with improvement of function were needed for an improvement of LVEF of
      >/=5%.

PMID- 14697460
TI  - Correlation of postpercutaneous coronary intervention creatine kinase-MB and
      troponin I elevation in predicting mid-term mortality.
AB  - Creatine kinase-MB (CK-MB) and troponin I elevations after successful
      percutaneous coronary intervention (PCI) are common, and different gradations
      have been correlated with mortality. To establish which of these 2 markers of
      myonecrosis, CK-MB and troponin I, accurately predicts mortality after successful
      PCI, we analyzed 2,873 patients without acute myocardial infarction who underwent
      PCI for in-hospital events and mid-term mortality. Patients were stratified into
      4 groups based on peak post-PCI cardiac markers values: group I: normal CK-MB
      (<16 U/L) or troponin I (<2 ng/ml); group II: CK-MB or troponin I levels 1 to 3
      times normal; group III: >3 to 5 times normal; and group IV: >5 times normal. CK
      MB elevation occurred in 16.1% of patients, with 12.2%, 2.3%, and 1.6% in groups
      II to IV, respectively. Troponin I elevation was detected in 38.9% of patients,
      with 16.4%, 8.4%, and 14.1% in groups II to IV, respectively. There was poor
      correlation between postprocedural CK-MB and troponin I values (r = 0.10) and in
      their individual subgroups. Kaplan-Meier estimates of death for postprocedure CK
      MB were 2.1%, 2.7%, 1.7%, and 10.3% (p = 0.002) for groups I to IV, respectively;
      for troponin I, these estimates were 2.2%, 2.3%, 2.9%, and 2.1% for groups I to
      IV, respectively (p = 0.58). A Cox proportional hazards model showed that CK-MB
      >5 times normal was the strongest predictor of mortality (hazard ratio 6.7, 95%
      confidence interval 1.9 to 22.9; p = 0.002), although heart failure, peripheral
      vascular disease, pre-PCI digoxin therapy, and post-PCI renal failure also
      predicted mortality. However, neither troponin I peak elevation nor any subgroup
      predicted mortality. Troponin I is frequently elevated after PCI, but does not
      predict mortality. Periprocedural CK-MB elevation >5 times normal remains an
      independent predictor of mid-term mortality and a valuable marker for PCI
      prognosis in low-to-medium risk patients.

PMID- 14697461
TI  - Usefulness of dipyridamole stress echocardiography for predicting graft patency
      after coronary artery bypass grafting.
AB  - Noninvasive techniques often provide controversial results in patients who have
      coronary artery bypass grafts (CABGs). Vasodilator stress echocardiography allows
      semi-simultaneous imaging of CABG flow and segmental left ventricular wall
      motion. To assess the comparative and additive value of regional flow and
      function for noninvasive evaluation of graft patency status, we evaluated 110
      consecutive patients who underwent CABG and who were scheduled for coronary
      angiography. All patients underwent stress echocardiography with dipyridamole
      (0.84 mg/kg) and atropine (1 mg), including wall motion analysis by 2-dimensional
      echocardiography and Doppler evaluation of flow reserve of each CABG.
      Echocardiographic findings were compared with angiographic data. Four patients
      had inadequate acoustic windows. The remaining 106 patients had 226 grafts
      performed. Stress echocardiography showed 67% sensitivity, 91% specificity, and
      71% accuracy for identification of 50% to 100% stenosis in the graft or in the
      recipient coronary vessel. There was a fair agreement with angiography (kappa
      coefficient 0.60). Identification of impaired coronary bypass flow reserve (i.e.,
      <1.9 for internal mammary grafts and <1.6 for saphenous vein grafts) by Doppler
      had 91% sensitivity, 88% specificity, and 89% accuracy for graft stenosis. There
      was good agreement with angiographic findings (kappa 0.77). The combination of
      the 2 techniques achieved 93% sensitivity, 93% specificity, and 93% accuracy,
      showing a very good agreement with the patency status of the grafts as evaluated
      at angiography (kappa 0.85). The combined assessment of wall motion and flow
      reserve in patients who underwent CABG is feasible and provides an accurate
      estimate of graft patency status by increasing sensitivity of stress
      echocardiography and specificity of Doppler flow reserve.

PMID- 14697462
TI  - Comparisons of effects of statins (atorvastatin, fluvastatin, lovastatin,
      pravastatin, and simvastatin) on fasting and postprandial lipoproteins in
      patients with coronary heart disease versus control subjects.
AB  - The effects of atorvastatin at 20, 40, and 80 mg/day on plasma lipoprotein
      subspecies were examined in a randomized, placebo-controlled fashion over 36
      weeks in 97 patients with coronary heart disease (CHD) with low-density
      lipoprotein (LDL) cholesterol levels of >130 mg/dl and compared directly with the
      effects of fluvastatin (n = 28), pravastatin (n = 22), lovastatin (n = 24), and
      simvastatin (n = 25). The effects of placebo and 40 mg/day of each statin were
      also examined in subjects with CHD with subjects in the fasting state and in the
      fed state 4 hours after a meal rich in saturated fat and cholesterol and compared
      with results in age- and gender-matched control subjects. At all doses tested in
      the fasting and fed states, atorvastatin was significantly (p <0.01) more
      effective in lowering LDL cholesterol and non-high-density lipoprotein (HDL)
      cholesterol than all other statins, and significantly (p <0.05) more effective
      than all statins, except for simvastatin, in lowering triglyceride and remnant
      lipoprotein (RLP) cholesterol. At 40 mg/day in the fasting state, atorvastatin
      was significantly (p <0.01) more effective than all statins, except for
      lovastatin and simvastatin, in lowering cholesterol levels in small LDL, and was
      significantly (p <0.05) more effective than all statins, except for simvastatin,
      in increasing cholesterol in large HDL and in lowering LDL particle numbers. Our
      data indicate that atorvastatin was the most effective statin tested in lowering
      cholesterol in LDL, non-HDL, and RLP in the fasting and fed states, and getting
      patients with CHD to established goals, with fluvastatin, pravastatin,
      lovastatin, and simvastatin having about 33%, 50%, 60%, and 85% of the efficacy
      of atorvastatin, respectively, at the same dose in the same patients.

PMID- 14697463
TI  - Comparison of cardiac structure and function in American Indians with and without
      the metabolic syndrome (the Strong Heart Study).
AB  - The metabolic syndrome (MS) is linked to cardiovascular risk. Recently, the Adult
      Treatment Panel (ATP) III provided new criteria for the definition of the MS. We
      analyzed the impact of the MS on cardiac structure and function and the
      independent association of the 5 different components of the ATP III-defined MS
      with cardiac markers of preclinical disease. Echocardiographic examination was
      performed in 612 nondiabetic participants with ATP III-defined MS and in 824
      participants without the MS. Participants with the MS were more often women (p
      <0.001) and had similar ages compared with those without the MS. After
      controlling for confounders, participants with the MS had greater left
      ventricular (LV) dimension, mass, and relative wall thickness, and left atrial
      diameter (all p </=0.01), and a higher prevalence of LV hypertrophy (p <0.001),
      with lower ejection fraction (p <0.05), midwall shortening (p <0.001), and mitral
      E/A ratio (p <0.05) than participants who did not have the MS. In multiple
      regression modeling, high blood pressure (BP) and abdominal obesity were the only
      components of the MS associated with increased LV diameter; only high BP was
      associated with increased LV mass and prevalence of LV hypertrophy (both p
      <0.001). When high to normal BP was present in the absence of hypertension, the
      MS exhibited LV geometry similar to hypertensive participants without the MS.
      Therefore, abnormal LV geometry and function are related to the MS. Increased BP
      is the component of the MS most strongly associated with cardiac markers of
      preclinical disease, even in the absence of traditionally defined hypertension.

PMID- 14697464
TI  - Comparison of recurrence rates after direct-current cardioversion for new-onset
      atrial fibrillation in patients receiving versus those not receiving rhythm
      control drug therapy.
AB  - The AFFIRM investigators have recommended rate control as the preferred strategy
      for recurrent atrial fibrillation (AF), but the appropriate strategy for new
      onset persistent AF is uncertain. Our study evaluated the AF recurrence rate and
      the impact of rhythm-control drugs (class 1A, 1C, and 3 antiarrhythmic drugs) on
      patients with new-onset persistent AF after successful direct-current (DC)
      cardioversion. Consecutive patients who underwent DC cardioversion of AF from
      January 1, 1996 to December 31, 1999 were screened for new-onset persistent AF,
      and 150 patients met the inclusion criteria. After the first DC cardioversion, 50
      patients received rhythm-control drugs (rhythm-control group) and the other 100
      did not (rate-control group). The 2 groups had similar clinical characteristics
      except for a lower ejection fraction (44 +/- 14% vs 49 +/- 14%, p <0.01) and a
      higher proportion of idiopathic dilated cardiomyopathy (20% vs 1%, p = 0.03) in
      the rhythm-control group versus the rate-control group. During the follow-up
      period there was a trend toward a lower rate of early AF recurrence at 24 hours
      after DC cardioversion in the rhythm-control group versus the rate-control group
      (6% vs 16%, p = 0.11), but there was a high recurrence rate of AF in both groups
      at 1 month (30% for the rhythm-control group vs 41% for the rate-control group, p
      = 0.25). At the end of the follow-up period, rhythm-control therapy was abandoned
      in 78% of the rhythm-control group patients after the failure of 1 to 3 rhythm
      control drugs. In the rate-control group, rhythm-control therapy was attempted
      after AF recurrence in 62 patients but was later abandoned in 48 patients (77%)
      because of treatment failure. Therefore, the high incidence of treatment failure
      with rhythm-control therapy suggests that rate control with anticoagulation
      should be preferred in patients with new-onset persistent AF if AF recurs after
      DC cardioversion.

PMID- 14697465
TI  - A comparison of pulmonary vein ostial anatomy by computerized tomography,
      echocardiography, and venography in patients with atrial fibrillation having
      radiofrequency catheter ablation.
AB  - Accurate assessment of pulmonary vein anatomy is important to procedures that
      isolate these structures in patients with atrial fibrillation. Various modalities
      of pulmonary vein (PV) imaging are employed in clinical practice; however, the
      consistency of findings among the different modalities is unknown. The purpose of
      this study is to compare PV ostial anatomy by 4 common imaging techniques. Twenty
      four patients undergoing catheter-based PV isolation procedures for atrial
      fibrillation had their PV ostial anatomy determined by cardiac computerized
      tomography (CT) and transesophageal echocardiography (TEE) before ablation and by
      intracardiac echocardiography (ICE) and venography during the ablation procedure.
      The number and maximal dimension of the PV ostia were determined by each imaging
      modality. In the 24 patients, 98 PV ostia were visualized by CT, 93 by ICE, 81 by
      TEE, and 71 by venography. The average ostial diameters were similar between CT
      (1.45 +/- 0.29 cm) and ICE (1.51 +/- 0.22 cm, p = 0.066). Compared with CT or
      ICE, the ostial diameters were larger with venography (1.67 +/- 0.32 cm) and
      smaller with TEE (1.16 +/- 0.28 cm, all p <0.001). PV ostial diameters as
      determined by ICE were significantly correlated with CT measurements (r = 0.57, p
      <0.001) and venography (r = 0.52, p <0.001). Venography measures of PV diameter
      were correlated with measures by CT (r = 0.33, p = 0.03). TEE measures were not
      correlated with any other modality (all p >/=0.43). CT identifies the greatest
      number of PV ostia followed by ICE. Venography overestimates and TEE
      underestimates ostial diameters compared with CT or ICE. The PV ostial dimensions
      obtained by ICE, CT, and venography are all significantly correlated.

PMID- 14697466
TI  - Risks for atrial fibrillation and congestive heart failure in patients >/=65
      years of age with abnormal left ventricular diastolic relaxation.
AB  - We sought to determine the risk for the first episodes of atrial fibrillation
      (AF) and congestive heart failure (CHF) in a cohort of patients aged >/=65 years
      who had abnormal left ventricular (LV) diastolic relaxation. Records were
      reviewed for all residents of Olmsted County, Minnesota, who had >/=1
      transthoracic echocardiogram performed at the Mayo Clinic between 1990 and 1998,
      and who were in sinus rhythm and did not have a history of AF, CHF, valvular or
      congenital heart disease, permanent pacemaker, or stroke. Of 994 patients who
      qualified and had LV diastolic function assessment, abnormal LV relaxation was
      identified in 569 (57%), 105 of whom (18%) developed a first episode of AF or CHF
      over a mean follow-up of 4.0 +/- 2.7 years. Age (p <0.0001), history of
      myocardial infarction (p <0.0001), history of diabetes mellitus (p = 0.041),
      electrocardiographic LV hypertrophy (p = 0.0223), and indexed left atrial (LA)
      volume (p = 0.0003) were independent predictors. A stepwise increase in age
      adjusted risk was evident when stratified by tertiles of indexed LA volume (<27
      ml/m(2); 27 to 37 ml/m(2); >37 ml/m(2)). Compared with patients with normal LV
      diastolic function (n = 148, 15%), the risks for first episodes of AF or CHF were
      not different in those with abnormal diastolic relaxation if LA volume was <27
      ml/m(2) (p = 0.303). In conclusion, these data suggest the presence of a wide
      spectrum of risks for AF or CHF in the elderly who have abnormal LV diastolic
      relaxation, with the highest risks evident in those with the largest left atria.
      When LA volume was <27 ml/m(2), however, the risks for these events were not
      different from those with normal LV diastolic function.

PMID- 14697467
TI  - Measures of heart period variability as predictors of mortality in hospitalized
      patients with decompensated congestive heart failure.
AB  - Depressed heart rate variability (HRV) is a powerful independent predictor of a
      poor outcome in patients with chronic and stable congestive heart failure (CHF).
      However, the prognostic value of HRV analysis in patients hospitalized for
      decompensated CHF is not known. The aim of this study was to investigate whether
      HRV parameters obtained during admission for decompensated CHF could predict
      survival after hospital discharge. We studied 199 patients (131 men, aged 60 +/-
      14 years) with a previous diagnosis of New York Heart Association class III or IV
      CHF who were admitted to the hospital for decompensated CHF. Twenty-four-hour
      Holter recordings were obtained on admission, and measures of HRV were calculated
      in the time and frequency domain. During a mean follow-up of 312 +/- 150 days, 40
      patients (21.1%) died. Kaplan-Meier analysis indicated that patients with SD of
      the RR intervals over a 24-hour period (p = 0.027), SD of all 5-minute mean RR
      intervals (p = 0.043), total power (p = 0.022), and ultra-low-frequency power (p
      = 0.008) in the lower tertile were at a higher risk of death. In a multivariate
      Cox regression model, the same indexes in the lower tertile were independent
      predictors of mortality: SD of the RR intervals over a 24-hour period (risk ratio
      [RR] 2.2, 95% confidence interval [CI] 1.05 to 4.3, p = 0.036), SD of all 5
      minute mean RR intervals (RR 2.1, 95% CI 1.05 to 4.2, p = 0.04), total power (RR
      2.2, 95% CI 1.08 to 4.2, p = 0.03), and ultra-low-frequency power (RR 2.6, 95% CI
      1.3 to 5.3, p = 0.007). Therefore, the severity of autonomic perturbations during
      hospital admission for CHF decompensation, as reflected by measures of overall
      HRV, can predict survival after hospital discharge. Together with previous
      studies, our findings suggest that indexes of overall HRV provide useful
      prognostic information in the full spectrum of CHF severity.

PMID- 14697468
TI  - Myocardial perfusion reserve and peripheral endothelial function in patients with
      idiopathic dilated cardiomyopathy.
AB  - The aim of this study was to assess the relation between peripheral endothelial
      function and myocardial perfusion reserve in patients with mild heart failure due
      to idiopathic dilated cardiomyopathy (IDC). Myocardial perfusion and brachial
      artery flow mediated dilation (FMD) were measured in 20 clinically stable
      patients with IDC (New York Heart Association classes I to III, ejection fraction
      35 +/- 9%) and 13 apparently healthy subjects who were matched for age and lipid
      profile. Resting and hyperemic (dipyridamole; 0.56 mg/kg/min) perfusion were
      measured using oxygen-15-labeled water and positron emission tomography (PET).
      Perfusion reserve was calculated as the ratio of hyperemic to resting perfusion.
      FMD was assessed by measuring the change in brachial artery diameter in response
      to reactive hyperemia. Patients with IDC had lower hyperemic perfusion (1.73 +/-
      0.83 vs 3.01 +/- 1.20 ml/min/g, p <0.001) and perfusion reserve (2.01 +/- 0.91 vs
      3.08 +/- 1.35, p <0.01) compared with healthy subjects. Brachial artery FMD,
      however, was not different from that of the healthy subjects. Furthermore,
      neither hyperemic perfusion nor perfusion reserve was correlated with FMD in the
      patients with IDC, whereas the healthy subjects demonstrated a positive
      correlation between FMD and perfusion reserve (r = 0.57; p = 0.04). Thus,
      abnormal myocardial perfusion characterizes patients with IDC. Myocardial
      perfusion reserve and peripheral endothelial function do not parallel each other
      in patients with IDC.

PMID- 14697469
TI  - Practical approach to incorporating new studies and guidelines for antiplatelet
      therapy in the management of patients with non-ST-segment elevation acute
      coronary syndrome.

PMID- 14697470
TI  - Atherosclerotic risk factors revisited.

PMID- 14697471
TI  - Influence of conduction disturbances on clinical outcome in patients with acute
      myocardial infarction receiving thrombolysis (results from the ARGAMI-2 study).
AB  - Right bundle branch block and complete atrioventricular (AV) block are conduction
      disorders (CDs) that have been observed in 14% of patients admitted with ST
      elevation acute myocardial infarction. CDs carry a poor prognosis, with a
      threefold increase in the mortality rate, mainly due to cardiogenic shock and
      recurrent fatal myocardial infarction at 1-year follow-up. According to
      multivariable analysis, CD was the second strongest predictor of death, after
      high Killip class. Compared with patients without CD, the 1-year outcome of
      patients with CD was identically worse, irrespective of whether CD appeared
      during admission, disappeared, or remained constant. Similar adverse outcomes
      were seen in patients with complete AV block and right bundle branch block.

PMID- 14697472
TI  - Results of cardiac rehabilitation in patients with diabetes mellitus.
AB  - To study the prevalence, risk profile, and outcomes of diabetics in cardiac
      rehabilitation, data on 952 consecutively enrolled patients were evaluated.
      Diabetics on entry had poor glycemic control, and compared with nondiabetics, had
      a greater adverse risk profile (body mass index, waist circumference,
      hypertension, triglycerides, peripheral vascular disease, and lower fitness
      levels), and a lower program adherence rate. Although exercise capacity
      significantly improved, it is clear from the outcomes reported in this study that
      more effective interventions in weight management, lipid lowering, and glycemic
      control are needed. This study emphasizes the need to identify diabetic patients
      in contemporary cardiac rehabilitation programs and target them for an aggressive
      program of risk factor management, including exercise training.

PMID- 14697473
TI  - Effect of atorvastatin 80 mg on endothelial cell function (forearm blood flow) in
      patients with pretreatment serum low-density lipoprotein cholesterol levels <130
      mg/dl.
AB  - The effect of 6-week treatment with 80 mg/day atorvastatin on vascular function
      in the forearm was investigated in 18 patients with mean pretreatment serum low
      density lipoprotein cholesterol concentrations of 112 +/- 4 mg/dl in a double
      blind, placebo-controlled, randomized study. Statin treatment improved hyperemic
      forearm blood flow and decreased serum markers of oxidative stress and
      inflammation.

PMID- 14697474
TI  - Comparison of ischemia-modified albumin levels in patients undergoing
      percutaneous coronary intervention for unstable angina pectoris with versus
      without coronary collaterals.
AB  - This study compared ischemia-modified albumin levels, a marker of ischemia in
      patients undergoing percutaneous coronary intervention. Ischemia-modified albumin
      levels were significantly lower in patients with collateral circulation compared
      with those without collateral circulation.

PMID- 14697475
TI  - Effectiveness of percutaneous coronary intervention in cardiac allograft
      vasculopathy.
AB  - Twenty-five heart transplant recipients underwent 45 coronary interventions at a
      mean of 7.8 +/- 2.2 years from time of transplant. Periprocedural success was
      high, and there was a trend toward better outcomes in the group that underwent
      stent deployment compared with conventional balloon angioplasty.

PMID- 14697476
TI  - Effect of fluvastatin on long-term outcome after coronary revascularization with
      stent implantation.
AB  - We assessed the impact of long-term fluvastatin treatment on adverse
      atherosclerotic cardiac events (cardiac death, myocardial infarction, and
      revascularization excluding repeat interventions due to restenosis in the first 6
      months) in 847 patients (fluvastatin [n = 417] or placebo [n = 430]) with average
      cholesterol levels treated with stents in the Lescol Intervention Prevention
      Study (LIPS). During the 4-year follow-up period, fluvastatin significantly
      decreased total cholesterol and low-density lipoprotein cholesterol levels and
      decreased the risk of first adverse atherosclerotic cardiac events by 30%
      compared with placebo (95% confidence interval -49 to -3.4, p = 0.03).

PMID- 14697477
TI  - Effectiveness and safety of manual hemostasis facilitated by the SyvekPatch with
      one hour of bedrest after coronary angiography using six-French catheters.
AB  - Manual hemostasis facilitated by a SyvekPatch with 1 hour of bedrest after
      coronary angiography using 6Fr catheters was evaluated in a study of 200
      patients. There were no major adverse events and 2% minor adverse events, all of
      which were managed successfully with additional bedrest of 1 to 2 hours. The
      findings suggest that the 1-hour bedrest protocol using the SyvekPatch is safe
      and effective in low-risk patients.

PMID- 14697478
TI  - Comparison of the effects of removal of chest hair with not doing so before
      external defibrillation on transthoracic impedance.
AB  - Chest hair contributes significantly to transthoracic impedance (TTI) during
      defibrillation. The magnitude of this effect has not been established using
      external paddles. We compared TTI in 40 men before elective cardiac surgery, and
      before and after shaving their chests. Chest hair causes a significant increase
      in TTI during external defibrillation, the magnitude of the effect being related
      to both the quantity of hair and force applied to the defibrillation paddles.
      When the chests of nonhirsute patients were shaved, a decrease in TTI occurred,
      which was probably related to the creation of low-impedance pathways through skin
      abrasions.

PMID- 14697479
TI  - Relation of response of subclinical atherosclerosis detected by electron beam
      tomography to baseline low-density lipoprotein cholesterol levels.
AB  - Calcified plaque progression by electron beam tomography was evaluated in 176
      aggressively treated asymptomatic patients. Similar plaque progression was noted
      irrespective of baseline low-density lipoprotein cholesterol levels, including
      those with low-density lipoprotein cholesterol <100 mg/dl. These findings
      indicate that subclinical atherosclerosis may respond to drug therapy in a
      fashion parallel to that of clinical disease demonstrated in the Heart Protection
      Study.

PMID- 14697480
TI  - CYP3A4 genotypes and plasma lipoprotein levels before and after treatment with
      atorvastatin in primary hypercholesterolemia.
AB  - To test whether genetic variation in the CYP system may influence the statin
      response, a promoter (A-290G) and 2 nonsynonymous polymorphisms (F189S and M445T)
      in the CYP3A4 gene locus were examined in 340 hypercholesterolemic patients who
      were treated with atorvastatin 10 mg. The A-290G variant allele was significantly
      associated with higher levels of post-treatment low-density lipoprotein
      cholesterol, whereas the M445T variant was associated with lower levels of low
      density lipoprotein cholesterol before and after treatment.

PMID- 14697481
TI  - Electrophysiologic predictors of the recurrence of persistent atrial fibrillation
      within 30 days of cardioversion.
AB  - Patients with recurrence of persistent atrial fibrillation within 30 days of
      cardioversion had slower atrial conduction, a slower sinus rate, no difference in
      the absolute value of the effective refractory period, greater early reverse
      remodeling of the effective refractory period, and more premature atrial
      contractions than those who did not. These findings highlight the role of slow
      conduction and premature atrial contractions in the pathophysiology of atrial
      fibrillation and suggest a possible proarrhythmic effect of reverse remodeling.

PMID- 14697482
TI  - New method for real-time discrimination and management of ventricular and
      supraventricular tachyarrhythmias applicable to patients with dual-chamber
      cardioverter-defibrillators.
AB  - In this study we describe a highly sensitive and specific method for
      discriminating between ventricular and supraventricular tachyarrhythmias based on
      the response to simultaneous atrial and ventricular antitachycardia pacing. This
      new method, which can terminate supraventricular tachycardias in >50% of
      patients, can be easily implemented in a new generation of dual-chamber
      defibrillators.

PMID- 14697483
TI  - Right ventricular diastolic function in patients with chronic aortic
      regurgitation.
AB  - Right ventricular diastolic function was evaluated using Doppler echocardiography
      in 40 patients with aortic regurgitation. Abnormal right ventricular relaxation
      and filling were the main findings of our study.

PMID- 14697484
TI  - Incidence, outcome, and risk factors for stroke after the Fontan procedure.
AB  - We reviewed records on patients who underwent hemi-Fontan and Fontan procedures
      over a 13-year period at a single institution to examine the incidence and
      outcome of stroke and to attempt to identify risk factors for stroke. A history
      of pulmonary artery banding was associated with an increased risk of stroke.

PMID- 14697485
TI  - Comparison of perception of health status by physicians, nurses, and patients in
      the Dual-chamber And VVI Implantable Defibrillator (DAVID) trial.
AB  - Previous studies have shown a poor correlation between health and quality-of-life
      assessments by patients, physicians, and nurses. Some have argued that patients
      are treated impersonally in clinical trials. Because one would expect that
      patient care would be compromised if this were the case, we used the Dual-chamber
      And VVI Implantable Defibrillator (DAVID) clinical trial setting to see if these
      assertions truly reflect the assessments of quality of life by health care
      professionals. Physicians, nurses, and patients in the DAVID trial had concordant
      assessments of the patients' perception of health status. The findings dispel
      assertions that patient concerns are not reliably assessed.

PMID- 14697486
TI  - Immunohistochemical testing for Helicobacter pylori infection in ascending aortic
      aneurysms and penetrating aortic ulcers.
AB  - Evidence implicating Helicobacter pylori (H. pylori) in coronary artery disease
      and aneurysmal lesions is controversial. No published data have related H. pylori
      infection to ascending aortic aneurysms and penetrating ulcers, although both of
      these lesions may have an infectious components in their initiating process. We
      sought to investigate possible H. pylori infection in 54 human specimens of 42
      aortic aneurysms and 12 penetrating ulcers. No evidence of H. pylori was found in
      these specimens.

PMID- 14697487
TI  - Miscellany.

PMID- 14697488
TI  - Evaluation of patients with chest pain.

PMID- 14697489
TI  - There is no "insignificant" coronary artery disease.

PMID- 14697491
TI  - Effects of dietary folic acid supplementation on cerebrovascular endothelial
      dysfunction in rats with induced hyperhomocysteinemia.
AB  - This study shows, for the first time, that hyperhomocysteinemia induces
      endothelial dysfunction in a rat brain, and that this can be alleviated by
      dietary folic acid supplementation. Our experiments examined the effects of folic
      acid supplementation on the endothelial nitric oxide synthase (eNOS) expression
      in the hyperhomocysteinemic rat brain, and related the observed changes in eNOS
      expression to the expression of the cell adhesion molecule and the glucose
      transporter protein. The animals were raised on an experimental diet containing
      0.3% homocystine for 2 weeks and then they were placed either on a 0.3%
      homocystine, 0.3% homocystine with 8 mg/kg folic acid, or folic acid (8 mg/kg)
      diet for 2 weeks. The cerebrovascular eNOS activity was examined
      immunohistochemically. Cerebral levels of eNOS, glucose transporter-1 (GLUT-1),
      and the vascular cell adhesion molecule-1 (VCAM-1) proteins were evaluated by
      Western blot analysis. At 4 weeks, the homocystine diet induced a fourfold
      increase in plasma homocysteine (control: 6.5+/-0.4 micromol/l, homocystine:
      26.2+/-2.5 micromol/l), and a reduction in the cerebral eNOS and GLUT-1
      expression levels with a concomitant increase in the level of VCAM-1 expression.
      Dietary folic acid supplementation caused a significant decrease in the plasma
      homocysteine levels, a concomitant increase in the hyperhomocysteinemia-induced
      reduction in the cerebral eNOS and GLUT-1 expression levels, and a decrease in
      the hyperhomocysteinemia-induced VCAM-1 expression levels.

PMID- 14697492
TI  - Discharge of inferior olive cells during reaching errors and perturbations.
AB  - It is widely believed that inferior olive (IO) neurons signal the occurrence of
      movement errors. The IO compares descending motor commands with information about
      movement and detects mismatches. Presumably, this error signal is used by the
      cerebellum to improve motor performance. To test this theory, we trained cats to
      reach out, grasp and retrieve a handle on cue. After training, the handle was
      displaced on selected trials so the cats would reach but miss the handle. Fifty
      five IO cells with receptive fields on the forelimb were tested with the
      displaced handle condition. No cell fired at or near the time of "expected"
      contact, but some cells fired when the cats struck objects while attempting to
      grasp. A mismatch between a motor command and expected result is not sufficient
      to activate IO neurons; appropriate stimulation must occur. To define conditions
      for appropriate stimulation, the limb was stimulated at various times during the
      task. Sixty-six cells (including the 55 tested under the displaced handle
      condition) were tested with mechanical stimulation during quiet stance, and 98%
      responded to stimulation. A smaller percentage (68%) fired when stimulation was
      introduced during the reaching task, and the probability of these responses
      varied with the subdivision of the olive as well as the phase of the task. We
      conclude that it is unlikely that IO discharge provides information about
      movement or movement error. Olivary cells respond reliably to appropriate
      somatosensory stimulation but not to active movement or movement error.

PMID- 14697494
TI  - Disposition of 1,2,3,4,-tetrahydroisoquinoline in the brain of male Wistar and
      Dark Agouti rats.
AB  - Direct evidence for accumulation of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endo
      and exogenous substance suspected of producing Parkinsonism in humans, has not
      yet been shown. This study aimed to examine TIQ disposition in the whole rat
      brain and in the striatum and substantia nigra (SN). TIQ was administered to male
      Wistar and Dark Agouti rats (20, 40 and 100 mg/kg i.p.) alone or jointly with
      specific CYP2D inhibitor quinine (20, 40, 80 mg/kg i.p.), acutely or chronically.
      TIQ concentration in brain of both strains was several-fold higher than in
      plasma. The level of its metabolite, 4-OH-TIQ, was very low in the brain and
      plasma of TIQ-treated Wistar while in those receiving additionally quinine or in
      Dark Agouti rats, 4-OH-TIQ was absent or negligible. Inhibition of CYP2D
      catalyzing TIQ 4-hydroxylation in the liver had no influence on TIQ accumulation
      in the brain. Exogenous TIQ was actively transported from periphery into the
      brain by the organic cation transporter system, mainly OCT3, and quickly
      eliminated from it by P-glycoprotein. TIQ accumulation after chronic injection to
      Wistar rats was short-lasting and limited to SN. High concentration of TIQ in SN
      induces while in the liver inhibits the nigral and hepatic activity CYP2D,
      respectively.

PMID- 14697493
TI  - Local anesthetic effects of cocaethylene and isopropylcocaine on rat peripheral
      nerves.
AB  - Cocaethylene is a naturally occurring cocaine derivative that has been used as a
      tool in both clinical studies of cocaine reward and as a potential model compound
      for agonist substitution therapy in cocaine dependence. It is equipotent to
      cocaine at inhibiting dopamine uptake in-vitro and in-vivo. Because it has been
      reported that local anesthetic properties may influence the reinforcing effects
      of dopamine uptake inhibitors, we investigated the local anesthetic properties of
      cocaethylene as well as isopropylcocaine, another potential pharmacological tool
      in studies of cocaine reward and agonist substitution therapy. We compared the
      efficacy of nerve impulse blockade by lidocaine, cocaine, cocaethylene and
      isopropylcocaine using rat sciatic nerves and dorsal roots (DRs). Nerves were
      placed in a modified sucrose gap chamber and repetitively stimulated at high
      frequency. The amplitude of compound action potentials (CAPs) at the beginning
      and end of each stimulus train was measured before and after exposure to each
      compound. All compounds produced concentration-dependent and use-dependent
      decrements in CAP amplitude, but cocaethylene and isopropylcocaine at medium to
      high concentration (0.375-1.875 mM) showed a more prolonged block after washout
      relative to cocaine or lidocaine. Patch clamp studies on dorsal root ganglion
      (DRG) neurons indicated a use-dependent blockade of sodium channels. These
      studies provide a more complete understanding of the pharmaocology of potential
      agonist treatment candidates, and suggest a mechanism whereby cocaethylene
      produces a decreased euphoria in humans compared to cocaine.

PMID- 14697495
TI  - Food deprivation after treatment blocks the multiple-day hyperphagic response to
      SHU9119 administration.
AB  - The multiple-day hyperphagic effect of the melanocortin 3/4 receptor antagonist,
      SHU9119, is apparently abolished when rats are food-deprived for 24 h after
      central (4th-ventricular) injection. Here, we affirmed this indication, and
      addressed the possibility that the orexigenic potency of SHU9119 is simply masked
      by the refeeding hyperphagia that follows food deprivation. This explanation is
      discounted by our finding that the drug response in ad libitum-fed rats and the
      deprivation response are expressed at different, and non-overlapping, times of
      day. We then asked whether food consumption during a hypothesized critical period
      in the hours after treatment is necessary for expression of the hyperphagic
      response to SHU9119, or alternatively, whether blood-borne signals that emerge
      only after an extended period of food restriction underlie the drug-state
      interaction. Evidence favoring the latter interpretation was derived from a
      series of four experiments over which the timing and duration of food access
      after drug administration was varied. The results indicate an interaction between
      melanocortin receptor activity and the metabolic state of the animal, and
      constrain our thinking about the peripheral signals and central mechanisms that
      underlie this interaction.

PMID- 14697496
TI  - Simultaneous analysis of the time course for changes in core body temperature,
      activity, and nociception following systemic administration of interleukin-1beta
      in the rat.
AB  - The aches and pains that accompany fever appear to be mediated, at least in part,
      by the peripheral release of cytokines such as interleukin-1beta (IL-1beta). The
      objective of this study was to determine, whether changes in nociceptive
      sensitivity produced by IL-1beta administration are temporally linked to changes
      in core body temperature. Experiment 1 examined nociceptive responsiveness for a
      period of 3 h following systemic administration of IL-1beta (1, 3, 10 and 20
      microg/kg). The two highest doses of IL-1beta produced a drop in temperature
      beginning approximately 60 min after cytokine administration. This hypothermia
      lasted 90 min and was associated with hyperalgesia. Experiment 2 examined changes
      in temperature and nociception for 12 h following administration of IL-1beta (10
      microg/kg). An early, short-lived hypothermia was followed by a significant
      hyperthermia from 3.25 to 6.5 h following IL-1beta administration. This late
      occurring fever was accompanied by hyperalgesia. Both the hypo- and hyperthermia
      phases were associated with a reduction in locomotor activity. Given that
      repeated nociceptive testing may confound assessment of temperature and activity,
      Experiment 3 examined the effects of IL-1beta (10 microg/kg) administration on
      temperature and activity in rats that remained in their home cages. The biphasic
      change in temperature and the reduction in activity were nearly identical to that
      reported in Experiment 2, indicating that repeated nociceptive testing did not
      confound these data. The results of this study demonstrate that, two phases of
      hyperalgesia occur and coincide with the periods of altered thermoregulation
      produced by systemic administration of IL-1beta.

PMID- 14697497
TI  - Prenatal protein deprivation in rats induces changes in prepulse inhibition and
      NMDA receptor binding.
AB  - Epidemiological studies suggest that prenatal malnutrition increases the risk of
      developing schizophrenia. Animal models indicate that prenatal protein
      deprivation (PPD) affects many aspects of adult brain function. We tested the
      hypothesis that PPD in rats would alter prepulse inhibition (PPI), which is an
      operational measure of sensorimotor gating that is deficient in schizophrenia
      patients. Additionally, we examined dopaminergic and glutaminergic receptor
      binding in the striatum and hippocampus, which have been suggested to play a role
      in the etiology of schizophrenia. Rat dams were fed normal (25%) or low (6%)
      protein diets beginning 5 weeks prior to, and throughout pregnancy. The pups were
      tested at postnatal days (PND) 35 and 56 for PPI. Striatal and hippocampal NMDA
      receptor, and striatal dopamine receptor binding were quantified post-mortem in a
      subset of these rats. Female rats exposed to PPD had reduced levels of PPI at PND
      56, but not PND 35, suggesting the emergence of a sensorimotor gating deficit in
      early adulthood. Striatal NMDA receptor binding was increased in PPD females. A
      decrease in initial startle response (SR) was also observed in all PPD rats
      relative to control rats. These results suggest that PPD causes age- and sex
      dependent decreases in PPI and increases in NMDA receptor binding. This animal
      model may be useful for the investigation of neurodevelopmental changes that are
      associated with schizophrenia in humans.

PMID- 14697498
TI  - Role of tumor necrosis factor receptor-1 in the death of retinal ganglion cells
      following optic nerve crush injury in mice.
AB  - To assess the specific role of tumor necrosis factor (TNF) death receptor
      signaling in the induction of retinal ganglion cell (RGC) death, optic nerves of
      mice deficient for TNF receptor-1 (TNF-R1-/-) and control mice (C57BL/6J) were
      unilaterally subjected to crush injury. Counts of RGCs and their axons 6 weeks
      after the injury demonstrated that their loss was significantly less in TNF-R1-/-
      mice compared to controls. The most prominent decrease in neuronal loss detected
      in TNF-R1-/- mice was beyond the initial 2-week period after the injury. This
      time period was correlated with the period of glial activation and increased
      glial immunolabeling for TNF-alpha in these eyes. No further protection against
      neuronal loss was detectable in TNF-R1-/- mice treated with D-JNKI1, a specific
      inhibitor of c-Jun N-terminal protein kinase (JNK). However, anti-JNK treatment
      of control animals provided a significant protection against neuronal loss during
      the same secondary degeneration period. Phospho-JNK immunolabeling of RGCs in
      control mice subjected to optic nerve crush significantly decreased following
      their treatment with D-JNKI1, and anti-JNK treatment protected RGCs from
      degeneration in these animals, similar to the lack of TNF-R1. These findings
      provide evidence that TNF death receptor signaling is involved in the secondary
      degeneration of RGCs following optic nerve injury, and is associated with JNK
      signaling. Since secondarily degenerating neurons are viable targets for
      neuroprotection, inhibition of TNF death receptor signaling may be an effective
      strategy to protect RGCs in several neurodegenerative injuries.

PMID- 14697499
TI  - Migration patterns of subventricular zone cells in adult mice change after
      cerebral cortex injury.
AB  - The subventricular zone (SVZ) generates the largest number of migratory cells in
      the adult brain. SVZ neuroblasts migrate to the olfactory bulbs (OB) in the
      adult, whereas during development, SVZ cells migrate into many adjacent nuclei.
      Previously, we showed that cerebral cortex injury in the adult causes molecular
      and cellular changes which may recapitulate the developmental migratory
      directions. Consistent with this, growth factors, as well as models of illness or
      injury can cause adult SVZ cells to migrate into non-olfactory bulb nuclei. Here,
      we tested the hypothesis that cerebral cortex injury in the adult mouse induces
      changes in migration, by labeling adult SVZ cells with a retroviral vector and
      examining the distribution of cells 4 days and 3 weeks later. Four days after
      cortical lesions, disproportionately fewer retrovirally-labeled cells had
      migrated to the olfactory bulb in lesioned mice than in controls. Conversely, the
      number of cells found in non-olfactory bulb regions (primarily the area of the
      lesion and the corpus callosum) was increased in lesioned mice. The morphology of
      these emigrated cells suggested that they were differentiating into glial cells.
      Three weeks after cortical injury, the majority of retrovirally-labeled cells in
      both groups of mice had migrated into the granule and periglomerular layers of
      the olfactory bulb. At 3 weeks, we still observed retrovirally-labeled glial
      cells in the corpus callosum and in the area of the injury in lesioned mice.
      These results suggest that cortical lesions cause a transient change in migration
      patterns of SVZ progeny, which is characterized by decreases in migration to the
      olfactory bulb but increased migration towards the injury. Our studies also
      suggest that cortical lesions induce the production of new glial cells which
      survive for at least 3 weeks after injury. The data support the concept that in
      the adult, SVZ cells can generate progeny that migrate towards injured areas and
      thus potentially be harnessed for neural repair.

PMID- 14697500
TI  - Antidromic discharges in dorsal roots of decerebrate cats. II: studies during
      treadmill locomotion.
AB  - In a previous companion paper [Brain Res. 846 (1999) 87-105] we have shown that
      the dorsal root activity of a decerebrate cat is composed of both orthodromic and
      antidromic discharges as determined by spike triggered averaging (STA).
      Furthermore we have shown that, during fictive locomotion in decerebrate and
      paralyzed cats, antidromic discharges peak in different parts of locomotion cycle
      but mainly in the flexion phase. In the present study, we have recorded unit
      potentials from dorsal rootlets during treadmill locomotion in order to
      understand better the role of movement-related feedback in the generation of
      antidromic potentials. The unitary activity of 92 antidromically discharging
      units was recorded in proximal stumps of cut dorsal roots, and that of 20 such
      units was recorded in uncut roots using two bipolar Ag/AgCl electrodes in both
      cases. The activity of 80% (74/92) units in cut filaments and of 70% (14/20)
      units in uncut ones was phasewise related to stepping movements. The peaks of
      activity of different units occurred during different phases of the step cycle
      both in cut and uncut filaments. In most cases, the peak of activity was
      superimposed upon a background of sustained discharge. After blocking the
      orthodromic flow in a filament (local anesthesia or distal section), the
      antidromic discharges continued to peak during the same phase but the rate of the
      discharges increased. We conclude that movement-related afferent feedback
      significantly modulates the antidromic discharges in dorsal roots during
      treadmill locomotion. We suggest that these antidromic discharges have a role in
      controlling afferent feedback during movement.

PMID- 14697501
TI  - 6-Hydroxydopamine increases the level of TNFalpha and bax mRNA in the striatum
      and induces apoptosis of dopaminergic neurons in hemiparkinsonian rats.
AB  - This study was focused on the apoptosis (programmed cell death) induction
      involved in the loss of dopaminergic (DA-ergic) neurons in 6-hydroxydopamine (6
      OHDA) hemiparkinsonian rats. The apoptosis in the striatum and substantia nigra
      pars compacta (SNpc), was examined 6, 24 h and 7 days after the 6-OHDA lesions
      employing the TUNEL method. The changes in mRNA levels of pro-apoptotic protein
      tumor necrosis factor alpha (TNFalpha) and its "death receptor" TNFalphaRI and
      then bax mRNA, as an important regulator of apoptotic neurodegeneration were
      followed by RT-PCR procedure. In situ analysis revealed an increased number of
      TUNEL-positive neurons in 6-OHDA-treated animals in all examined time points. The
      highest number of apoptotic neurons was detected 24 h after the lesion, both in
      the ipsilateral striatum (3.41+/-0.18) and SNpc (5.8+/-0.79). A significant
      increase in the level of TNFalpha mRNA was observed in 6-OHDA-lesioned striatum,
      with maximal value after 24 h (46%) comparing to the control. In contrast, 6-OHDA
      did not significantly change the level of TNFalphaRI mRNA in any time point. Six
      and 24 h post-operatively, we observed a significant increase of bax mRNA
      expression (40% and 45%, respectively) in the ipsilateral striatum of treated
      animals in comparison with the right striatum of the controls. However, the
      highest level of the bax mRNA expression was reached 7 days after the surgery
      (94%) in the ipsilateral striatum of 6-OHDA-treated animals. These results
      suggest that striatal injection of 6-OHDA can induce early changes that would be
      an important regulator of apoptotic neurodegeneration of dopamine-producing
      neurons, during the first post-operative week.

PMID- 14697502
TI  - Septal infusions of glucose or pyruvate with muscimol impair spontaneous
      alternation.
AB  - This experiment examined the effects of co-infusing the GABA agonist muscimol
      (0.5 nmol) with 33 nmol of glucose, pyruvate, fructose or sorbitol into the
      medial septum on spontaneous alternation. Only co-infusions of muscimol with
      glucose or pyruvate impaired spontaneous alternation performance; none of the
      other infusions had any significant effects. The findings suggest that glucose
      metabolism rather than hyperosmolarity is involved in the memory-impairing
      interaction between glucose and muscimol.

PMID- 14697503
TI  - Vesicular glutamate transporters in the lateral geniculate nucleus: expression of
      VGLUT2 by retinal terminals.
AB  - We used immunohistochemistry to localize vesicular glutamate transporters VGLUT1
      and VGLUT2 in the rat lateral geniculate nucleus. The lateral geniculate nucleus
      is intensely immunoreactive for both transporters. Monocular eye removal
      abolished staining for VGLUT2 in a pattern corresponding to the distribution of
      terminals from the missing eye, without affecting distribution of VGLUT1
      immunoreactivity. These data indicate retinal ganglion cells are the source of
      VGLUT2-containing synapses in the lateral geniculate nucleus.

PMID- 14697504
TI  - Low-frequency stimulation of trigeminal afferents induces long-term depression of
      human sensory processing.
AB  - Electric low-frequency stimulation (LFS) of afferent nerve fibers reliably
      induces long-term depression (LTD) of synaptic transmission in vitro. LTD is
      suggested to be one important mechanism of synaptic plasticity in the mammalian
      brain. The study demonstrated an LTD of evoked cortical potentials (-30%) and
      perception ratings (-25%) by noxious electric LFS of trigeminal afferents in man,
      indicating that LTD may also be involved in human synaptic plasticity.

PMID- 14697505
TI  - Pediatric neuroblastomas: genetic and epigenetic 'danse macabre'.
AB  - Neuroblastomas are the most frequently occurring solid tumors in children under 5
      years. Spontaneous regression is more common in neuroblastomas than in any other
      tumor type, especially in young patients under 12 months. Unfortunately, the full
      clinical spectrum of neuroblastomas also includes very aggressive tumors,
      unresponsive to multi-modality treatment and accounting for most of the pediatric
      cancer mortalities under 5 years of age. It is generally emphasized that more
      than one biological entity of neuroblastoma exists. Structural genetic defects
      such as amplification of MYCN, gain of chromosome 17q and LOH of 1p and several
      other chromosomal regions have proven to be valuable as prognostic factors and
      will be discussed in relation to their clinical relevance. Recent research is
      starting to uncover important molecular pathways involved in the pathogenesis of
      neuroblastomas. The aim of this review is to discuss several important aspects of
      the biology of the neuroblast, such as the role of overexpressed oncogenes like
      MYCN and cyclin D1, the mechanisms leading to decreased apoptosis, like
      overexpression of BCL-2, survivin, NM23, epigenetic silencing of caspase 8 and
      the role of tumor suppressor genes, like p53, p73 and RASSF1A. In addition, the
      role of specific proteins overexpressed in neuroblastomas, such as the
      neurotrophin receptors TrkA, B and C in relation to spontaneous regression and
      anti-angiogenesis will be discussed. Finally, we will try to relate these
      pathways to the embryonal origin of neuroblastomas and discuss possible new
      avenues in the therapeutic approach of future neuroblastoma patients.

PMID- 14697506
TI  - Genomic organization of a novel root alliinase gene, ALL1, in onion.
AB  - Alliinase operates in the biochemical pathway that produces the compounds
      responsible for the characteristic flavor of onion. We isolated and characterized
      the 86-kb BAC clone containing a novel onion alliinase gene, ALL1. Identity of
      deduced amino acid sequence of ALL1 with a bulb alliinase is 65.4% and with a
      root alliinase is 67.3%. The ALL1 gene is expressed specifically in onion roots
      and estimated pI value of mature ALL1 protein is similar to that of root
      alliinase isoform I, which is an uncharacterized protein having alliinase
      activity. The highly repetitive sequences around the ALL1 gene was observed from
      sequence and DNA gel blot analyses. The 33.2% G+C content of the 35-kb ALL1
      region is similar to that of dicot plants and lower than that of monocot cereal
      plants, although onion is classified into monocots. The present study shows the
      first evidence of the onion genomic sequences around genes differed from the
      cereal genome.

PMID- 14697507
TI  - Gene structure and evolution of Tieg3, a new member of the Tieg family of
      proteins.
AB  - TGF beta-inducible immediate early gene, Tieg, belongs to the superfamily of Sp1
      like transcription factors containing three C(2)H(2)-zinc finger DNA binding
      motifs close to the C-terminus. So far, Tieg1 and Tieg2 have been identified in
      human and mouse. We identified Tieg3, a new member of the Tieg protein family by
      screening a mouse cDNA library. Tieg3 has almost all the known features of the
      Tieg protein family: it shares a highly conserved C(2)H(2) zinc finger DNA
      binding domain and is 96% identical to Tieg2 and 86% to Tieg1, respectively. In
      addition, the three repression domains at the N-terminus, R1, R2 and R3 are
      conserved in all the Tiegs. Similar to Tieg1 and Tieg2, Tieg3 mRNA is up
      regulated in response to TGF beta 1 treatment and can perform the Sp1 sites
      mediated repression of transcription. A 4 kilobase (kb) long transcript of mouse
      Tieg3 can be detected using Northern-blot analysis. The gene of mouse Tieg3
      contains four exons. Due to the amino acid sequence similarity, mouse Tieg2 is
      regarded as an orthologue of human Tieg2. However, the mouse Tieg3 gene is
      localized in a conserved segment on mouse chromosome 12 corresponding to human
      Tieg2 on chromosome 2 with the same gene order. An interesting explanation for
      this apparent contradiction might be a homologous recombination leading to loci
      exchange between the mouse Tieg3 and Tieg2.

PMID- 14697508
TI  - Cloning, sequencing, and biochemical characterization of the nostocyclopeptide
      biosynthetic gene cluster: molecular basis for imine macrocyclization.
AB  - Nostocyclopeptides A1 and A2 are novel cyclic heptapeptides produced by the
      terrestrial cyanobacterium Nostoc sp. ATCC53789 that possess a unique imino
      linkage in the macrocyclic ring. Herein we report the cloning, sequencing,
      annotation, and biochemical analysis of the 33-kb nostocyclopeptide (ncp)
      biosynthetic gene cluster, which includes seven open reading frames predicted to
      be involved in the biosynthesis and transport of these natural products. The
      genetic architecture and domain organization of the ncpA-B nonribosomal peptide
      synthetase (NRPS) is co-linear in arrangement with respect to the putative order
      of the biosynthetic assembly of the cyclic peptide. A reductase domain identified
      at the C-terminal end of the NRPS NcpB is predicted to catalyze an NAD(P)H
      mediated hydride transfer to the heptapeptidyl-S-enzyme intermediate NH(2)-Tyr
      Gly-DGln-Ile-Ser-mPro-Leu/Phe-S-NRPS to yield a linear heptapeptide aldehyde that
      is subsequently captured intramolecularly with the amino group of the N-terminal
      amino acid residue tyrosine to form a stable imine bond. While a few C-terminal
      reductases associated with NRPSs have been identified, the ncp reductase is the
      first to mediate imine macrocyclization involving peptide N- and C-termini.
      Biochemical analysis of the NcpA1 and NcpB1 adenylation domains coupled with the
      recent characterization of the (2S,4S)-5-hydroxyleucine dehydrogenase NcpD, which
      is involved in the biosynthesis of the nonproteinogenic amino acid residue L-4
      methylproline from L-leucine, support the involvement of this cluster in
      nostocyclopeptide biosynthesis.

PMID- 14697509
TI  - Identification and expression analysis of two IFN-inducible genes in crucian carp
      (Carassius auratus L.).
AB  - Interferon (IFN) exerts its antiviral effects mainly through activation of a
      subset of IFN-stimulated genes (ISG), but relatively few of fish ISGs have been
      isolated and characterized so far. Here, we report two fish ISGs, termed CaIFI58
      and CaIFI56, cloned from a subtractive cDNA library constructed with mRNAs
      obtained from crucian carp (Carassius auratus L.) blastulae embryonic (CAB) cells
      infected by UV-inactivated GCHV and mock-infected cells. Database search revealed
      that both ISGs had a high-level homology with all members of a well conserved
      gene family with multiple tetratricopeptide repeat (TPR) motifs, including human
      IFI60, IFI58, IFI56, IFI54 and their homologues in some other mammalian species.
      The transcripts of CaIFI58 and CaIFI56 were undetectable in CAB cells but could
      be induced by active GCHV, UV-inactivated GCHV or CAB IFN. Analysis of expression
      difference between them and IFN signal factors, CaSTAT1 and CaIRF7, indicated
      that their transcriptions were mediated possibly through JAK-STAT signal pathway,
      which was further supported by the induction analysis in UV-inactivated GCHV
      infected, IFN-treated and untreated cells in the presence or absence of
      cycloheximide (CHX), a potent inhibitor of protein synthesis. In addition, a
      pufferfish (Fugu rubrides) DNA sequence representing putative FrIFI56 was also
      revealed when CaIFI58 and CaIFI56 were used to search the pufferfish genome
      database. Phylogenetic analysis showed that these fish ISGs form a unique clad
      independent of mammalian homologues, reflecting a distant evolutionary
      relationship from mammals. These studies identified the first teleost IFI56 and
      IFI58 orthologues.

PMID- 14697510
TI  - Genomic organization and characterization of the promoter for the E2A gene.
AB  - Although E2A gene products are ubiquitously expressed, E2A-deficient mice display
      selective abnormalities in lymphocyte development, suggesting a certain
      requirement of the E2A gene products during lymphocyte development. To gain
      insights into the mechanisms of E2A transcriptional regulation, we isolated the
      genomic clones which are composed of four exons and one noncoding exon and span
      approximately 16 kb. The promoter region of E2A gene lacks a TATA box, and primer
      extension analysis showed several transcription initiation sites, a feature that
      characterizes TATA-less promoters. The transient transfection assay using the 5'
      flanking region (positions -2994/+62) revealed that both positive (-357/-158) and
      negative (-831/-358) regulatory segments control E2A transcription in B-cell
      (WEHI-231) and T-cell (DO11.10) lines. However, contribution of a certain segment
      to promoter activity was different between lymphocytes and fibroblasts (NIH-3T3).
      Sequential deletion analysis of the constructs spanning the positive regulatory
      segments showed that the segment -257/-238 played a critical role in the basal
      promoter activity of the E2A gene, although other segments within -337 to -158
      also appeared to be involved. Mutational analysis using the -257/-238 fragment
      failed to demonstrate a single cis-element responsible for the basal promoter
      activity, suggesting that E2A promoter requires the interaction of multiple
      regulatory elements. Electrophoretic mobility shift assay (EMSA) demonstrated a
      highly specific complex comprised of a positive regulatory segment (-267/-238)
      and putative transcription factor(s), which might be necessary for the basal
      promoter activity of the E2A gene.

PMID- 14697511
TI  - Identification of Krit1B: a novel alternative splicing isoform of cerebral
      cavernous malformation gene-1.
AB  - Cerebral cavernous malformations (CCM) are vascular malformations, mostly located
      in the central nervous system, which occur in 0.1-0.5% of the population. They
      are characterized by abnormally enlarged and often leaking capillary cavities
      without intervening neural parenchyma. Some are clinically silent, whereas others
      cause seizures, intracerebral haemorrhage or focal neurological deficits. These
      vascular malformations can arise sporadically or may be inherited as an autosomal
      dominant condition with incomplete penetrance. At least 45% of families affected
      with cerebral cavernous malformations harbour a mutation in Krev interaction
      trapped-1 (Krit1) gene (cerebral cavernous malformation gene-1, CCM1). This gene
      contains 16 coding exons which encode a 736-amino acid protein containing three
      ankyrin repeats and a FERM domain. Neither the CCM1 pathogenetic mechanisms nor
      the function of the Krit1 protein are understood so far, although several
      hypotheses have been inferred from the predicted consequences of Krit1 mutations
      as well as from the identification of Krit1 as a binding partner of Rap1A, ICAP1A
      and microtubules. Here, we report the identification of Krit1B, a novel Krit1
      isoform characterized by the alternative splicing of the 15th coding exon. We
      show that the Krit1B splice isoform is widely expressed in mouse cell lines and
      tissues, whereas its expression is highly restricted in human. In addition, we
      developed a real-time PCR strategy to accurately quantify the relative ratio of
      the two Krit1 alternative transcripts in different tissues, demonstrating a
      Krit1B/Krit1A ratio up to 20% in mouse thymus, but significantly lower ratios in
      other tissues. Bioinformatic analysis using exon/gene-prediction, comparative
      alignment and structure analysis programs supported the existence of Krit1
      alternative transcripts lacking the 15th coding exon and showed that the splicing
      out of this exon occurs outside of potentially important Krit1 structural domains
      but in a region required for association with Rap1A, suggesting a subtle, yet
      important effect on the protein function. Our results indicate that maintenance
      of a proper ratio between Krit1A and Krit1B could be functionally relevant and
      suggest that the novel Krit1B isoform might expand our understanding of the role
      of Krit1 in CCM1 pathogenesis.

PMID- 14697512
TI  - An atypical topoisomerase II sequence from the slime mold Physarum polycephalum.
AB  - We have determined the complete nucleotide sequence of the cDNA encoding DNA
      topoisomerase II from Physarum polycephalum. Using degenerate primers, based on
      the conserved amino acid sequences of other eukaryotic enzymes, a 250-bp fragment
      was polymerase chain reaction (PCR) amplified. This fragment was used as a probe
      to screen a Physarum cDNA library. A partial cDNA clone was isolated that was
      truncated at the 3' end. Rapid amplification of cDNA ends (RACE)-PCR was employed
      to isolate the remaining portion of the gene. The complete sequence of 4613 bp
      contains an open reading frame of 4494 bp that codes for 1498 amino acid residues
      with a theoretical molecular weight of 167 kDa. The predicted amino acid sequence
      shares similarity with those of other eukaryotes and shows the highest degree of
      identity with the enzyme of Dictyostelium discoideum. However, the enzyme of P.
      polycephalum contains an atypical amino-terminal domain very rich in serine and
      proline, whose function is unknown. Remarkably, both a mitochondrial targeting
      sequence and a nuclear localization signal were predicted respectively in the
      amino and carboxy-terminus of the protein, as in the case of human topoisomerase
      III alpha. At the Physarum genomic level, the topoisomerase II gene encompasses a
      region of about 16 kbp suggesting a large proportion of intronic sequences, an
      unusual situation for a gene of a lower eukaryote, often free of introns.
      Finally, expression of topoisomerase II mRNA does not appear significantly
      dependent on the plasmodium cycle stage, possibly due to the lack of G1 phase or
      (and) to a mitochondrial localization of the enzyme.

PMID- 14697513
TI  - Structural characterization and promoter analysis of human potassium channel
      Kv8.1 (KCNV1) gene.
AB  - The voltage-gated K(+) channel (Kv) family comprises four subfamilies: Kv1, Kv2,
      Kv3 and Kv4. Kv6, Kv7, Kv8 and Kv9 subfamilies have also recently been reported.
      The gene for Kv8.1 (KCNV1) maps onto chromosome 8q23.3, a locus for benign adult
      familial myoclonic epilepsy. Despite sequence identity with other K(+) channel
      genes, KCNV1 does not display K(+) channel activity when expressed in Xenopus
      oocytes, instead inhibiting activity of Kv2 and Kv3 channels. The present study
      investigated the molecular structure of KCNV1. In silico analysis detected a new
      5' noncoding exon, which extended the reported cDNA sequence to approximately 600
      bp. A promoter motif was found only in the upstream region of the newly detected
      exon 1. To determine the transcriptional mechanism of KCNV1, we generated a
      series of deletion mutants and random mutants, and examined promoter activities
      using the luciferase system. Three Sp1 motifs were found to be active in the core
      promoter sequence, spanning from nt -1350 to -911 (A of the ATG initiation codon
      was counted as +1). At least two additional sequences were detected as essential
      elements for promoter activity. A possible alternative 3' end was also detected
      at 280 bp downstream from the reported 3' end. These results provide useful
      information in developing KCNV1 screening for epileptic disease.

PMID- 14697514
TI  - The bovine (Bos taurus) CD11a-encoding cDNA: molecular cloning, characterisation
      and comparison with the human and murine glycoproteins.
AB  - The bovine cDNA encoding CD11a, a cell-surface glycoprotein involved in multiple
      leukocyte functions, was sequenced and compared with the human and murine
      sequences. Despite some focal differences, it shares all the main characteristics
      of its known mammalian homologs. Along with the bovine CD18-encoding cDNA, which
      is available for a long time, the sequence data provided here will allow the
      successful expression of bovine CD11a, thus giving the first opportunity to
      express the Bos taurus beta(2)-integrin CD11a/CD18 (LFA-1, alpha(L)beta(2)) in
      vitro as a tool to examine the specificities of inflammation in the bovine
      species.

PMID- 14697515
TI  - An abundant placental transcript containing an IAP-LTR is allelic to mouse
      pregnancy-specific glycoprotein 23 (Psg23): cloning and genetic analysis.
AB  - Several families of endogenous retroviruses (ERVs) are expressed in mammalian
      placental tissues, and are implicated in aspects of placental development and
      function. We characterized the structure of abundant ERV-related transcripts in
      mouse placenta. In addition to the 7 kb full-length type I and 5 kb type I
      deleted intracisternal A-particle (IAP) transcripts, we identified and cloned an
      abundant 2 kb transcript encoding a novel member of the pregnancy-specific
      glycoprotein (Psg) gene family, which contains an IAP long terminal repeat (LTR)
      in the 3' untranslated region (UTR). The polyadenylation signal for the
      transcript is provided by the inserted LTR sequence. This sequence is allelic to
      Psg23 and is therefore denoted as Psg23(LTR). The transcript encodes a protein of
      471 amino acids and has a domain organisation similar to previously described Psg
      proteins. Modelling of the protein N-domain produced a structure in good
      agreement with an existing crystalline structure for mouse sCEACAM1a. The LTR
      insertion is widely distributed among inbred mouse strains but is not found in
      129/sv, CBA/2, or in wild mice. Cloning of the genomic region downstream of the
      LTR insertion site from the C57Bl/6J strain indicates that the insertion consists
      of a solo LTR without additional IAP sequence, and identified the original Psg23
      polyadenylation signal sequence downstream of the insertion site. Psg23(LTR) was
      mapped to proximal chromosome 7 using the European collaborative interspecific
      mouse backcross (EUCIB) panel, and to yeast artificial chromosome (YAC) E072,
      which contains other members of the Psg gene family, by polymerase chain reaction
      (PCR). Northern blot analysis of RNA from adult and fetal mouse tissues and in
      situ hybridization to mid-gestation mouse embryos indicated that Psg23(LTR) is
      expressed predominantly in placental spongiotrophoblast. We detected a small, but
      statistically non-significant, bias in favour of transmission of Psg23(LTR) to
      the offspring of heterozygous parents. However, a larger study would be required
      to determine whether this allele is selectively advantageous to the developing
      embryo.

PMID- 14697516
TI  - Characterization of the Anaplasma marginale msp2 locus and its synteny with the
      omp1/p30 loci of Ehrlichia chaffeensis and E. canis.
AB  - Major surface protein 2 (MSP2) is an immunodominant and antigenically variant
      protein in the outer membrane of the rickettsia Anaplasma marginale. MSP2
      variation is generated by recombination into a single operon-linked genomic
      expression site. The complete 5.6-kb msp2 locus was identified by sequencing a 90
      kb region of the St. Maries strain of A. marginale. The locus encoded, in a 5' to
      3' direction, a transcriptional regulator followed by five outer membrane
      proteins, OMP1, OpAG3, OpAG2, OpAG1, and MSP2. The sequences of this entire locus
      were analyzed using six genetically and phenotypically distinct strains of A.
      marginale. The overall locus structure was highly conserved with 100% identity
      among strains in the transcriptional regulator. Synonymous and nonsynonymous
      exchanges were infrequent in omp1 and rare in opag1 and opag2 among the six
      strains without strong bias for either type of exchange (neutral mutations). In
      contrast, mutations in opag3 seem to underlie purifying (negative) selection
      reflecting pressure to retain protein structure, in marked contrast to the highly
      antigenically variant MSP2. Interestingly, the 5' structure of this A. marginale
      msp2 locus is conserved in the omp1 gene locus of Ehrlichia chaffeensis and p30
      gene locus of E. canis despite marked divergence between genera in the structure
      of the 3' region of the loci. This supports the hypothesis that the expression
      sites of these important immunogenic proteins are derived from a common precursor
      with later divergent evolution along genus lines.

PMID- 14697517
TI  - Identification of 24 genes and two pseudogenes coding for olfactory receptors in
      Japanese loach, classified into four subfamilies: a putative evolutionary process
      for fish olfactory receptor genes by comprehensive phylogenetic analysis.
AB  - Twenty-four olfactory receptor (OR) genes and two pseudogenes have been
      identified in the genome of Japanese loach (Misgurnus anguillicaudatus). The
      genes were classified into four subfamilies according to the similarity of the
      amino acid sequences. In each subfamily, members showed high sequence similarity
      not only to each other but also to orthologues of other fish species. The number
      of members in each OR subfamily was roughly estimated to be from 3 to 10 by
      genomic Southern blot analysis. The genes of all four OR subfamilies were shown
      to express on olfactory neurons of the olfactory epithelium by in situ
      hybridization analysis. Two major features of fish OR genes were found by
      comprehensive and comparative analyses on OR genes of Japanese loach and other
      fish species including catfish, zebrafish and pufferfish. First, the phylogenetic
      tree comprising of representative subfamily members suggests the existence of
      several prototype genes common to the genomes of many fish species. Second, when
      all members of orthologous subfamilies identified in each clade of the tree are
      integrated, the members of a single species comprise a monophyletic group. This
      means that 'intraspecies' sequence homology, that is, homology among paralogous
      genes of the same subfamily in a species, is higher than 'interspecies' homology,
      that is, homology between orthologous genes of different species. This suggests
      that the subfamily members of a species have evolved recently. Taken together,
      fish OR genes have evolved from a limited number of prototype genes common to
      most fish species, and several genes in a subfamily have diversely evolved in
      each species from each prototype.

PMID- 14697518
TI  - The global regulator GacS of a biocontrol bacterium Pseudomonas chlororaphis O6
      regulates transcription from the rpoS gene encoding a stationary-phase sigma
      factor and affects survival in oxidative stress.
AB  - The global regulator, GacS (global activator for antibiotics and cyanide sensor
      kinase), of the rhizosphere bacterium Pseudomonas chlororaphis O6 (Pc O6) was
      required for increased resistance to hydrogen peroxide as cultures mature.
      Specific bands of peroxidase and catalase activity were absent in the stationary
      phase cells of the Pc O6 gacS mutant, whereas a manganese superoxide dismutase
      (MnSOD) isozyme was expressed earlier and to a greater extent than in the wild
      type. In the wild-type cell, transcript accumulation of rpoS was higher in late
      logarithmic (log)-phase cells than cells from mid log-phase or stationary-phase.
      Transcript abundance from rpoS was reduced in the gacS mutant throughout the
      growth phase compared to the wild-type expression. The sequence of a small RNA,
      rsmZ, found downstream of rpoS in other pseudomonads was lacking in Pc O6. This
      RNA is implicated in the control of genes activated by the GacS system. Thus, the
      mechanism by which GacS mediates the activation of genes under its control
      requires further investigation in Pc O6.

PMID- 14697519
TI  - Genomic organization and differential splicing of the mouse and human Pcyt2
      genes.
AB  - CTP: ethanolaminephosphate cytidylyltransferase (Pcyt2) is an important
      regulatory enzyme in phosphatidylethanolamine and plasmalogen biosynthesis. We
      cloned the mouse gene mPcyt2 and established its relationship with the human
      homolog PCYT2. The two genes share similar size and contain two conserved
      catalytic domains but exhibit different exon/intron organization. An internal
      region could be alternatively spliced producing a longer mouse transcript, mPcyt2
      alpha, and a shorter human transcript, PCYT2 beta. The spliced region is entirely
      made from mPcyt2 Exon 7 and encodes the peptide PPHPTPAGDTLSSEVSSQ, located
      upstream of the second catalytic motif HIGH. Mouse and human proteins also differ
      in amino acid composition at the C-terminus due to an additional splicing between
      Exons 13 and 14 in PCYT2. The 5' RACE analyses and subsequent cloning of the
      promoter regions demonstrated that the mPcyt2 and PCYT2 promoters are located
      immediately upstream of the first exon. There is no sequence homology between the
      two promoters but they are both TATA-less, have conserved CAAT boxes at a
      matching distance (-85/-70 bp) from the transcription start site and contain cis
      elements for transcription factors of the CAAT, Sp1 and NF1 family, all in
      accordance with ubiquitous expression of both genes. The mPcyt2 gene is highly
      expressed in liver, brain, adipose tissues, heart, skeletal muscle, spleen, lungs
      and kidney. In THP-1 and U937 cells, PCYT2 expression could vary with the stage
      of cell differentiation. Luciferase reporter analyses show that the Pcyt2 and
      PCYT2 promoters are strong promoters similar to other ubiquitous promoters, such
      as those of Pcyt1 and SV-40.

PMID- 14697520
TI  - Cloning, characterization and comparative analysis of pig plasma apolipoprotein A
      IV.
AB  - Pig apolipoprotein (apo) A-IV cDNA was cloned, characterized and compared to the
      human ortholog. Mature porcine apo A-IV consists of 362 amino acids and displays
      a 75.6% sequence identity with human protein. Pig apo A-IV is the smallest
      reported mammalian apo A-IV because it lacks the repeated motifs of glutamine and
      glutamic acid at the carboxyl terminus. A phylogenic tree of apo A-IV mammalian
      proteins reveals that porcine apo A-IV is more closely related to humans and
      primates than to rodents. This protein is highly hydrophobic and is mainly
      associated with lipoproteins.

PMID- 14697521
TI  - Base composition and expression level of human genes.
AB  - It is well known that the gene distribution is non-uniform in the human genome,
      reaching the highest concentration in the GC-rich isochores. Also the amino acid
      frequencies, and the hydrophobicity, of the corresponding encoded proteins are
      affected by the high GC level of the genes localized in the GC-rich isochores. It
      was hypothesized that the gene expression level as well is higher in GC-rich
      compared to GC-poor isochores [Mol. Biol. Evol. 10 (1993) 186]. Several features
      of human genes and proteins, namely expression level, coding and non-coding
      lengths, and hydrophobicity were investigated in the present paper. The results
      support the hypothesis reported above, since all the parameters so far studied
      converge to the same conclusion, that the average expression level of the GC-rich
      genes is significantly higher than that of the GC-poor genes.

PMID- 14697522
TI  - Two novel isoforms of Adam23 expressed in the developmental process of mouse and
      human brains.
AB  - A metalloprotease and disintegrin (ADAM) is a family of membrane-anchored
      proteins and all family members have a multi-domain structure containing a zinc
      metalloprotease domain and a disintegrin domain that may serve as an integrin
      ligand. Here we reported two novel mammalian transcripts of Adam23, named Adam23
      beta and Adam23 gamma, to be involved in the development and functional
      activities of mammalian brains. Adam23 gamma was isolated from a 22-week human
      fetal brain cDNA library, using an EST homologous to Adam as a probe, and is 100%
      homologous to human Adam23 (Adam23 alpha) except that it lacks a fragment of 91
      bp near the C-terminal, thus it could not form obvious transmembrane domain.
      Adam23 beta was discovered while the diversity at the transmembrane domain (TM)
      was analyzed. Adam23 beta has a different sequence in the 91 nucleotides and thus
      encode different transmembrane domain. Adam23 beta and Adam23 gamma are mainly
      expressed in brain like Adam23 alpha. RT-PCR experiments in mouse brain also
      detected the two isoforms, consistent with observation of Northern analysis of
      human RNAs. Furthermore, results of RT-PCR amplification of Adam23 gamma in mouse
      brains of different developmental stages revealed a developmentally regulated
      expression pattern: Adam23 gamma is expressed in embryonic and infant brain, and
      disappeared after the 10th postnatal day. This temporally changing expression
      pattern of Adam23 gamma suggests that ADAM23 gamma likely plays an important role
      in brain development.

PMID- 14697523
TI  - Divergent evolution of the prolactin-inducible protein gene and related genes in
      the mouse genome.
AB  - The prolactin-inducible protein (PIP/GCDFP15) family consists of small secretory
      polypeptides that are found in various body fluids. In order to study
      evolutionary events to this family, we cloned member genes and analyzed their
      sequences. A database search revealed the presence of a novel paralogous gene on
      mouse chromosome 6q34 and a nonprocessed pseudogene adjacent to PIP on human
      chromosome 7q34. The mouse PIP and four related genes displayed higher
      nonsynonymous and synonymous substitution ratios in comparison to other mammalian
      PIP orthologues; furthermore, these genes exhibited distinct distributions among
      tissues such as seminal vesicle, colon, and mammary gland. A pair of duplicated
      genes could have existed prior to radiation to the human and rodents. While only
      PIP is active in the human lineage, species-specific gene duplications have given
      rise to functional variants in rodents. Adaptive evolution potentially has
      occurred among the PIP and its related genes in the mouse genome.

PMID- 14697524
TI  - Development of a rapid yeast estrogen bioassay, based on the expression of green
      fluorescent protein.
AB  - The aim of this study was to develop an estrogen transcription activation assay
      that is sensitive, fast and easy to use in the routine screening of estrogen
      activity in complex matrices such as agricultural products. Recombinant yeast
      cells were constructed that express the human estrogen receptor alpha (ER alpha)
      and beta-Galactosidase (beta Gal), Luciferase (Luc) or yeast Enhanced Green
      Fluorescence Protein (yEGFP) as a reporter protein. Compared to other yeast
      assays, these new cells contain both the receptor construct as well as the
      reporter construct stably integrated in the genome with only one copy of the
      reporter construct. Dose-response curves for 17beta-estradiol (E2) obtained with
      the beta Gal assay were similar to those reported and the calculated EC(50) of
      0.2 nM was even slightly better. However, 5 days of incubation were required
      before the chlorophenol red product could be measured. The Luc assay was as
      sensitive as the beta Gal assay and gave an EC(50) of 0.2 nM, but the signals
      were rather low and, although the assay can be performed within 1 day, the
      procedure is laborious and caused variability. The yEGFP revealed an EC(50) of
      0.4 nM, but compared to the beta Gal and the Luc assay, the response was much
      better. This yEGFP assay can be performed completely in 96 well plates within 4 h
      and does not need cell wall disruption nor does it need the addition of a
      substrate. This makes the test sensitive, rapid and convenient with high
      reproducibility and small variation. These qualities make that this yEGFP assay
      is suited to be used as a high throughput system.

PMID- 14697634
TI  - A novel tricolor, dual-fusion fluorescence in situ hybridization method to detect
      BCR/ABL fusion in cells with t(9;22)(q34;q11.2) associated with deletion of DNA
      on the derivative chromosome 9 in chronic myelocytic leukemia.
AB  - Dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) can
      accurately detect and quantify cells with BCR/ABL fusion in <1% of 500 nuclei in
      80% of patients with chronic myelocytic leukemia (CML) and t(9;22)(q34;q11.2).
      The remaining patients have one of three forms of atypical D-FISH patterns; these
      patterns have different sensitivities to detect disease. Neoplastic cells with
      one ABL, one BCR, and one BCR/ABL fusion are particularly problematic, because
      normal cells with coincidental overlap have the same pattern. For these patients,
      the normal cutoff for D-FISH is >23%. We tested a new method that incorporates an
      aqua-labeled probe for the argininosuccinate synthetase (ASS) gene into the
      conventional BCR/ABL D-FISH probe set. This tricolor D-FISH (TD-FISH) method
      takes advantage of the aqua-labeled ASS probe to distinguish between neoplastic
      and normal cells. We used TD-FISH to study 20 normal specimens and 35 specimens
      from 20 patients with known loss of both BCR and ABL from the derivative
      chromosome 9. The results show that TD-FISH effectively discriminates between
      cells with overlapping BCR and ABL signals from cells with true BCR/ABL fusion
      and improves the ability to quantify minimal residual disease from >23% to >1% of
      500 interphase nuclei.

PMID- 14697636
TI  - Characterization of gains, losses, and regional amplification in testicular germ
      cell tumor cell lines by comparative genomic hybridization.
AB  - We have performed comparative genomic hybridization on 12 testicular germ cell
      tumor (TGCT) cell lines and one paraffin-embedded surgical specimen to identify
      and characterize genome-wide gains and losses of chromosomes in these specimens.
      All specimens demonstrated overrepresentation of 12p. Other significant
      chromosomal gains, apart from 12p, included the X chromosome and chromosome arms
      1q and 20q. Chromosomal losses were observed for chromosomes 4 and 18 and
      chromosome arms 2q, 9q, and 13q. Genomic differences were observed between an
      embryonal carcinoma component of a mixed tumor, 833K, and its cisplastin
      resistant derivative line, 64CP, including losses of 6q23 approximately qter and
      9p22 approximately q21. Five lines also demonstrated gain of 12p and additional
      12p12 approximately p13 material. Similarly, two lines demonstrated gain of 12p
      and additional 12p11.2 approximately p12 material. The data supports the
      consistent gain of 12p in adult TGCT cell lines and additional regional
      amplification of 12p in some lines. This regional amplification has been observed
      in both primary tumor specimens and TGCT cell lines and may support a hypothesis
      that at least two different regions of 12p, one proximal and one distal, harbor
      genes important for the pathogenesis of testicular germ cell neoplasia.

PMID- 14697635
TI  - A recurrent gain of chromosome arm 3q in primary squamous carcinoma of the
      vagina.
AB  - Primary carcinomas of the vagina are rare tumors, accounting for 2%-3% of all
      gynecologic malignancies. Only a few karyotypes based on chromosome banding
      techniques have been reported. We have, therefore, used comparative genomic
      hybridization to establish a pattern of genomic imbalances in vaginal squamous
      cell carcinomas. Analysis of 16 formalin-fixed and paraffin-embedded tumors
      revealed that 70% of vaginal carcinomas carry relative copy number increases that
      map to chromosome arm 3q. Other recurring gains were observed on chromosome arms
      5p and 19p. Chromosomal losses were infrequent. Most tumors were aneuploid, as
      measured by image cytometry on Feulgen-stained tissue sections. The cytogenetic
      data were related to the presence of human papillomavirus genomes, expression of
      laminin-5 as a marker for invasiveness, and expression levels of markers for
      proliferative activity and mutated TP53. All relevant clinical data were
      recorded. The results suggest that vaginal carcinomas are defined by a specific
      distribution of chromosomal aneuploidies and that the pattern of genomic
      imbalances is strikingly similar to that observed in squamous cell carcinomas of
      the uterine cervix. Age at diagnosis (P=0.031), tumor size (P=0.025), and
      increased laminin-5 expression (P=0.006) have a significant influence on the
      survival time.

PMID- 14697637
TI  - Cytogenetic and fluorescence in situ hybridization characterization of clonal
      chromosomal aberrations and CCND1 amplification in esophageal carcinomas.
AB  - Cytogenetic analyses of four squamous cell carcinomas (SCC) of the esophagus
      showed complex numerical and structural abnormalities. Chromosomal bands or
      regions preferentially involved were 11q13, 8q10, 21q10, 3p10 approximately p11,
      1p11 approximately q11, 5p11 approximately q11, and 14p11 approximately q11. For
      the first time, to our knowledge, recurrent aberrations were identified in
      esophageal SCC, including homogeneous staining region (hsr), isochromosomes i(3q)
      and i(21q), and ring chromosome. Losses of chromosomal material dominated over
      gains. Recurrent imbalances included under-representation of 4p13 approximately
      pter, 5q14 approximately qter, 9p22 approximately pter, 10p, 11p13 approximately
      pter, 12p13 approximately pter, 17p10 approximately pter, 18p11 approximately
      pter, 21p, and 22p, as well as over-representation of 1q25 approximately qter,
      3q, 7q, and 8q. Interestingly, hsr at different chromosomal regions occurred in
      three of four cases. With the application of fluorescence in situ hybridization
      (FISH) and multicolor combined binary ratio labeling-FISH with specific DNA
      probes, it could be shown that in two cases the hsr was derived from chromosome
      11 material and that the amplicon included CCND1. Our results, together with
      previous molecular genetic findings, indicate that CCND1might be a prime target
      in 11q13 amplification, and that amplification of this gene might be crucial in
      the tumorigenesis of esophageal SCC. These observed chromosomal aberrations and
      imbalances thus provide important information for further molecular genetic
      investigation of esophageal SCC.

PMID- 14697638
TI  - Massive hyperdiploidy and tetraploidy in acute myelocytic leukemia and
      myelodysplastic syndrome.
AB  - Massive hyperdiploidy (>50 chromosomes) and tetraploidy (4n) are rare cytogenetic
      abnormalities in myelocytic malignancies, and their significance is unknown. We
      report on 11 patients with acute myelocytic leukemia (AML) and two patients with
      a myelodysplastic syndrome (MDS) with massive hyperdiploidy (10 patients) or
      tetraploidy (3 patients) seen at our institution over a 12-year period. Eleven
      patients were male and two were female. Age range was 44-84 years (median, 70
      years). Only one AML patient had a previous MDS, and no patient had therapy
      related disease. One or more copies of chromosomes 8 and 19 were gained in eight
      patients each; other frequently gained chromosomes included 13, 15, and 21. Eight
      patients had structural abnormalities in addition to chromosome gain; del(5q) was
      most common (five patients). Eleven patients received induction chemotherapy, but
      only four achieved complete remission. Survival ranged from 1 to 22 months, with
      a median of 6 months. We conclude that massive hyperdiploidy and tetraploidy are
      infrequent abnormalities in AML and MDS, are seen primarily in de novo disease in
      older male patients and are associated with a low remission rate and short
      survival. Massive hyperdiploidy and tetraploidy define a prognostically
      unfavorable cytogenetic group in de novo AML.

PMID- 14697639
TI  - Molecular cytogenetic characterization of rhabdomyosarcoma cell lines.
AB  - Alveolar rhabdomyosarcomas (ARMS) are soft-tissue tumors that are genetically
      characterized by the presence of reciprocal translocations that generate the
      fusion gene PAX3-FOXO1A or PAX7-FOXO1A. For the study of the biologic
      consequences of such rearrangements, several cell lines have been generated.
      However, established cell lines accumulate chromosome and genetic aberrations
      that make it difficult to draw significant conclusions. We have applied a set of
      techniques that includes spectral karyotyping, fluorescence in situ hybridization
      (FISH), comparative genomic hybridization (CGH), and microarray CGH, to the most
      commonly used cell lines carrying the two fusion genes that are present in ARMS.
      We have identified the bacterial artificial chromosomes that cover the
      breakpoints at genes PAX3, PAX7, and FOXO1A, which can be used as FISH probes for
      the translocations. The RH30 cell line, positive for the PAX3-FOXO1A fusion gene,
      was found to be highly complex: wide range of chromosome number, more than 50
      chromosome rearrangements, amplification of the hybrid gene, 24 DNA changes
      detected by conventional CGH, and 21 gene copy changes detected by microarray CGH
      (including several high-level amplifications). RMZ-RC2 cell line, positive for
      the PAX7-FOXO1A, was in the near-tetraploid range with only nonclonal structural
      rearrangements, amplification of the hybrid gene, 24 DNA changes by CGH, and 8
      gene copy changes, confirming the previously reported high-level amplification of
      MYCN.

PMID- 14697640
TI  - Molecular cytogenetic abnormalities in patients with concurrent chronic
      lymphocytic leukemia and multiple myeloma shown by interphase fluorescence in
      situ hybridization: evidence of distinct clonal origin.
AB  - The coexistence of chronic lymphocytic leukemia (CLL) and multiple myeloma (MM)
      is rare, and there is no consensus about the clonal relationship of the two
      disorders when they occur in the same individual. We investigated chromosomal
      abnormalities in two patients with concurrent CLL and MM using interphase
      fluorescence in situ hybridization (FISH) with a panel of region-specific DNA
      probes. In patient 1, the clonal plasma cells harbored IgH translocations
      (14q32); however, FISH with probes for the four most frequent IgH partner genes
      in MM (CCND1, FGFR3, MAF, and MYC) did not detect translocations involving any of
      them. The CLL cells were characterized by deletions of 13q14, 11q23, and 17p13,
      as well as trisomy 12, none of which were found in the MM cells. In patient 2,
      deletions of 13q14 and 17p13 were detected in CLL cells, but no cytogenetic
      abnormalities were found in the MM cells. Both patients had relapsed MM following
      chemotherapy and had autologous stem-cell transplant, whereas their CLL has been
      stable and not requiring treatment. Our results show that the cytogenetic
      profiles differ between CLL and MM within the same patients, and provide evidence
      for two distinct malignant clones in both patients.

PMID- 14697641
TI  - Characterization of psu dic(6;5)(p21.3;q13) with reverse chromosome painting in a
      patient with secondary myelodysplastic syndrome following treatment for multiple
      myeloma.
AB  - We report a case of a psu dic(6;5)(p21.3;q13) in a patient with secondary
      myelodysplastic syndrome (sMDS) following treatment for multiple myeloma. The
      abnormal chromosome was isolated by flow karyotyping and initially identified by
      reverse chromosome painting. The findings were then confirmed by forward
      painting. The value of flow karyotyping as a diagnostic technique in hematologic
      malignancies is discussed.

PMID- 14697642
TI  - Chromosomal comparative genomic hybridization abnormalities in early- and late
      onset human breast cancers: correlation with disease progression and TP53
      mutations.
AB  - Nearly 30% of the breast cancer patients in the Taiwanese community have their
      diseases diagnosed before the age of 40. Their 5-year survival rate is poorer
      than that of their late-onset breast cancer counterparts. Genomic abnormalities
      between these two breast cancer age groups were compared using comparative
      genomic hybridization (CGH) analyses. The sample set was made up of 44 early
      onset (<35 years old) and 54 late-onset cases (>63 years old). Frequent CGH
      changes were noted, such as gains on 8q, 1q, and 17q and losses on 16q, 17p, and
      8p. These were very similar for the two age groups, as well as for Taiwanese
      women and other ethnic populations. In contrast, several less common lesions,
      such as gains on 16p and 8p and losses on 11q and 9p, were significantly
      different between the early- and late-onset breast tumors. In addition, more
      profound chromosomal changes were consistently associated with the more advanced
      stage tumors, and less expression of the estrogen and the progesterone receptors,
      and of HER-2/neu. About 19% of the breast cancers examined carried a TP53
      mutation in exons 4-9. Of these, 88% (15/17) were missense point mutations and
      these were distributed randomly along the tested gene fragments without apparent
      clustering, as has been shown in certain other ethnic or regional studies. On
      average, patients carrying these TP53 mutations had 9.5 CGH lesions per case,
      compared to only 2.8 changes in samples that had no TP53 mutation. Our results
      indicate that certain genomic lesions, especially 11q loss, may play a role in
      early-onset breast tumor formation, and that combined use of genomic patterns and
      molecular targets may provide a useful tool for diagnostic, therapeutic, and
      prognostic purposes.

PMID- 14697643
TI  - Chromosome analyses of 16 cases of Wilms tumor: different pattern in unfavorable
      histology.
AB  - Cytogenetic analyses of 16 cases of Wilms tumor with abnormal karyotypes were
      reviewed, 15 cases of unilateral tumor and 1 bilateral. Three tumors exhibited an
      unfavorable histology (i.e., anaplastic changes); the rest fell into the
      favorable histology group. Of the 17 tumors with abnormal clonal aberrations, 9
      tumors were hyperdiploid (53%), 7 had pseudodiploid karyotypes (41%), and 1 was
      hypodiploid (6%). The most common numerical aberrations in descending order of
      frequency were gain of chromosomes 12, 8, and 6 and loss of chromosome 16.
      Structural rearrangements mostly involved chromosome 1, followed by chromosomes
      7, 14, and 17. Clustering of breaks around 1p22 approximately p31-->pter
      resulting in partial loss of 1p was the most frequent structural aberration.
      Additionally, i(7q) was observed as a sole abnormality in two tumors and a 7p
      translocation in two other tumors. Two other recurrent abnormalities were a
      partial deletion of 14q, seen in three tumors, and complete loss of chromosome 14
      in one tumor. All three Wilms tumors with unfavorable histology had abnormalities
      of 17p, resulting in TP53 gene deletion. These findings provide further support
      for the importance of gains of chromosomes 12, 8, and 6 and loss of 1p in the
      development of Wilms tumor. The results also support the association of
      unfavorable-histology Wilms tumors with TP53 deletion. The nonrandom losses of
      16/16q, 7p, and 14q may point to the importance of genomic imbalance in the
      pathogenetic consequences and progression of Wilms tumor.

PMID- 14697644
TI  - Cytogenetic and fluorescence in situ hybridization studies in 60 patients with
      multiple myeloma and plasma cell leukemia.
AB  - We report cytogenetic results in a series of 60 patients affected with multiple
      myeloma (MM) and plasma cell leukemia (PCL) and compare the results with those
      previously reported. In our series, a total of 41% of MM patients and 71% of PCL
      patients displayed chromosome abnormalities. To evaluate the clinical value of
      monosomy 18, we obtained fluorescence in situ hybridization results (using
      centromeric probe for chromosome 18) of 22 MM patients who displayed a normal
      karyotype. Monosomy 18 was present in 3 of 22 patients (14%). Using conventional
      cytogenetics, we detected monosomy 18 in one patient affected with PCL. Two of
      four cases with monosomy 18 followed an aggressive course, with overall survival
      of 1 and 9 months. The remaining two are in follow-up and remain stable. The
      association of monosomy 18 with IgA subtype predominance and poor prognosis was
      not observed in this series of MMs and PCLs. Although these results do not
      confirm our previous hypothesis, further observations of this group of patients
      (with monosomy 18) regarding malignant transformation is warranted.

PMID- 14697645
TI  - A novel t(2;17) in transformation of essential thrombocythemia to acute
      myelocytic leukemia.
AB  - A transformation of essential thrombocythemia to acute myelocytic leukemia (AML),
      myelodysplastic syndrome, or agnogenic myelocytic metaplasia is a relatively rare
      event. It occurs in 1%-4.5% of all patients with either treated or untreated
      essential thrombocythemia. Cytogenetic changes in the transformation to AML are
      common. We report the case of a patient treated for essential thrombocythemia
      with hydroxyurea for 49 months. He developed AML with a t(2;17), which to our
      knowledge has not been described in the literature.

PMID- 14697646
TI  - Establishment of cell lines from a primary hepatocellular carcinoma and its
      metastatis.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies in the
      world with a very poor prognosis that has been associated with tumor metastasis.
      The molecular mechanism of HCC metastasis is still unclear. In this study, we
      established cell lines from a primary tumor (H2-P) and its metastasis (H2-M). G
      banding karyotyping, comparative genomic hybridization, and fluorescence in situ
      hybridization were applied to study these two cell lines and the results
      demonstrated that they are of the same origin. These cell lines provide a very
      useful tool to identify genetic alterations associated with HCC metastasis.

PMID- 14697647
TI  - Neuroblastoma in chromosomal breakage syndromes.

PMID- 14697648
TI  - Re: Characterization of the A673 cell line (Ewing tumor) by molecular cytogenetic
      techniques.

PMID- 14697649
TI  - Constitutional t(8;22) in a patient with myasthenia gravis, leukocytosis, and
      thrombocytosis.

PMID- 14697650
TI  - Acute myelocytic leukemia with rare t(2;11)(q31;p13), skin rash, and fever of
      unknown origin.

PMID- 14697653
TI  - The neuronal adaptor protein Fe65 is phosphorylated by mitogen-activated protein
      kinase (ERK1/2).
AB  - Fe65 is a neuronal adaptor protein that binds a number of ligands and which
      functions in both gene transcription/nuclear signalling and in the regulation of
      cell migration and motility. These different functions within the nucleus and at
      the cell surface are mediated via Fe65's different binding partners. An
      Fe65/APP/TIP60 complex is transcriptionally active within the nucleus and an
      Fe65/APP/Mena complex probably regulates actin dynamics in lamellipodia. The
      mechanisms that regulate these different Fe65 functions are unclear. Here, we
      demonstrate that Fe65 is a phosphoprotein and, using mass spectrometry
      sequencing, identify for the first time in vivo phosphorylation sites in Fe65. We
      also show that Fe65 is a substrate for phosphorylation by the mitogen-activated
      protein kinases ERK1/2. Our results provide a mechanism by which Fe65 function
      may be modulated to fulfil its various roles.

PMID- 14697654
TI  - Neurotrophin-3 signaling maintains maturational homeostasis between neuronal
      populations in the olfactory epithelium.
AB  - Neurons within the olfactory system undergo functional turnover throughout life.
      This process of cell death and compensatory neurogenesis requires feedback
      between neuronal populations of different developmental ages. We examined the
      role of NT-3 in this process. NT-3 was localized within both the olfactory bulb
      and olfactory epithelium. Mice null for NT-3 showed increased numbers of immature
      neurons, without change in the number of mature neurons. This was due to
      compensatory alterations in apoptosis of mature and immature neuronal
      populations. Using a primary olfactory neuronal culture, NT-3 was found to
      directly activate the PI3K/Akt pathway and indirectly activate the MAPK and PLC
      pathways. Activated PI3K/Akt promoted mature neuronal survival and induced the
      release of secondary factors, which activated the MAPK and PLC pathways to reduce
      neuronal precursor proliferation and inhibit neuronal maturation. These effects
      of NT-3 serve to maintain homeostasis between neuronal populations within the
      olfactory epithelium.

PMID- 14697655
TI  - Response of motoneurons to neonatal sciatic nerve axotomy in Bax-knockout mice.
AB  - Neonatal motoneurons (MNs) die rapidly after axotomy, a response that is mediated
      by the pro-apoptotic gene Bax and is followed by a mitochondria-mediated
      apoptotic cascade. Although motoneurons in neonatal Bax-deficient mice fail to
      degenerate following axotomy, it has not been previously examined whether the
      rescued MNs can regenerate following injury. We report here that although spinal
      MNs in Bax-knockout (Bax-KO) mice survive indefinitely, they undergo severe
      atrophy by 14 days after axotomy. By 1 month following axotomy, MN regeneration
      was observed and cellular atrophy was partially reversed. Interestingly, we
      observed that all MNs, including those previously rescued from normal
      developmental cell death in the embryo by Bax deletion, exhibit a regenerative
      response to peripheral nerve injury. The regenerative response may be mediated by
      specific trophic factors because the expression of glial cell line-derived
      neurotrophic factor (GDNF) was greatly increased in the proximal stump of injured
      nerves and application of a GDNF-blocking antibody greatly reduced
      regeneration/regrowth of rescued MNs in Bax-KO mice. These results indicate that
      MNs rescued from developmental or injury-induced cell death by Bax deletion have
      the potential to regenerate or regrow in response to nerve-derived signals
      following neonatal axotomy.

PMID- 14697656
TI  - Development of cerebellar modules: extrinsic control of late-phase zebrin II
      pattern and the exploration of rat/mouse species differences.
AB  - The vertebrate cerebellum is divided into a characteristic set of 13 parasagittal
      "bands" or modules that are revealed in many different domains-ranging from
      patterns of gene and protein expression to the organization of afferent input. We
      have used the expression of Zebrin II/aldolase C in Purkinje cells as a marker of
      these bands and have discovered several new features of their regulation. We find
      that appearance of the banded expression of aldolase C during development differs
      between rat and mouse. In agreement with previous reports there is, in rat, a
      transient period during which all Purkinje cells are positive for aldolase C
      expression. By contrast, in mouse, the pattern emerges in its adult (banded) form
      from the earliest postnatal times. This species difference is found in both mRNA
      and protein expression. There also appears to be a transition that occurs in vivo
      between postnatal days 8 and 10. Slice cultures established from cerebella at the
      younger age do not develop a complete banding pattern, even after 6 days in
      culture. Slice cultures established from postnatal day 10 mice develop the full
      pattern within 2 days. This difference cannot be overcome by manipulating the
      levels of neuronal activity in the cultures. Thus some event must occur in vivo
      that "releases" the adult pattern and allows it to be realized in the more
      artificial situation of the slice culture. Taken together the results offer a
      more complete picture of the regulation of the aldolase C gene in cerebellar
      Purkinje cells and suggest important species differences in its developmental
      expression pattern.

PMID- 14697657
TI  - Meningeal cell-derived semaphorin 3A inhibits neurite outgrowth.
AB  - The neural scar that forms after injury to the mammalian central nervous system
      is a barrier to sprouting and regenerating axons. In addition to reactive
      astrocytes that are present throughout the lesion site, leptomeningeal
      fibroblasts invade the lesion core. When isolated in vitro, these cells form a
      very poor substrate for growing neurites, even more so than reactive astrocytes.
      Nevertheless the molecular mechanisms involved in this growth inhibition are not
      well understood. Semaphorins have been reported to be upregulated in meningeal
      cells (MCs) on mechanical injury to the brain and spinal cord. In the present
      study, we show that Sema3A mRNA and active protein are produced by cultured
      meningeal cells. A protein extract from these cells induces the collapse of
      embryonic dorsal root ganglion (DRG) growth cones. This collapsing activity is
      partially blocked by neuropilin-1 antibodies and is absent in meningeal cells
      derived from Sema3A-knockout mice. In addition to growth cone collapse,
      recombinant Sema3A but not Sema3C inhibits neurite outgrowth of embryonic DRGs.
      Consistent with this result we find that the inhibitory effect of meningeal cells
      on neurite outgrowth is partially overcome on Sema3A-deficient MCs. Furthermore
      we show that the inhibitory effect of MC-derived Sema3A on neurite outgrowth is
      modulated by nerve growth factor. Our results show that Sema3A, a chemorepellent
      during nervous system development, is a major neurite growth-inhibitory molecule
      in meningeal fibroblasts and is therefore likely to contribute to the inhibitory
      properties of the neural scar.

PMID- 14697658
TI  - The astrocyte/meningeal cell interface is a barrier to neurite outgrowth which
      can be overcome by manipulation of inhibitory molecules or axonal signalling
      pathways.
AB  - Invading meningeal cells form a barrier to axon regeneration after damage to the
      spinal cord and other parts of the CNS, axons stopping at the interface between
      meningeal cells and astrocytes. Axon behavior was examined using an in vitro
      model of astrocyte/meningeal cell interfaces, created by plating aggregates of
      astrocytes and meningeal cells onto coverslips. At these interfaces growth of
      dorsal root ganglion axons attempting to grow from astrocytes to meningeal cells
      was blocked, but axons grew rapidly from meningeal cells onto astrocytes.
      Meningeal cells were examined for expression of axon growth inhibitory molecules,
      and found to express NG2, versican, and semaphorins 3A and 3C. Astrocytes express
      growth promoting molecules, including N-Cadherin, laminin, fibronectin, and
      tenascin-C. We treated cultures in various ways to attempt to promote axon growth
      across the inhibitory boundaries. Blockade of NG2 with antibody and blockade of
      neuropilin 2 but not neuropilin 1 both promoted axon growth from astrocytes to
      meningeal cells. Blockade of permissive molecules on astrocytes with N-Cadherin
      blocking peptide or anti beta-1 integrin had no effect. Manipulation of axonal
      signalling pathways also increased axon growth from astrocytes to meningeal
      cells. Increasing cAMP levels and inactivation of rho were both effective when
      the cultures were fixed in paraformaldehyde, demonstrating that their effect is
      on axons and not via effects on the glial cells.

PMID- 14697659
TI  - RNA transport in oligodendrocytes from the taiep mutant rat.
AB  - The results presented here identify a new RNA trafficking phenotype in taiep
      oligodendrocytes that increases the frequency of reversals and restricts the
      extent of transport of RNA containing the A2RE transport signal from MBP mRNA.
      The taiep rat is a myelin mutant characterized by excessive accumulation of
      microtubules in oligodendrocytes and myelin deficiency in the central nervous
      system. The taiep RNA trafficking is developmentally correlated with the
      microtubule accumulation in oligodendrocytes and can be partially suppressed by
      reducing microtubule density with nocodazole or inhibiting dynein activity by
      coinjecting anti-dynein antibodies. These results suggest that RNA trafficking in
      taiep oligodendrocytes is inhibited by enhanced dynein activity that neutralizes
      or lessens the normal overriding power of the plus-end directed motor kinesin.
      Altered orientation of microtubules in oligodendrocyte fine processes and a
      physical barrier created by densely packed microtubules may also contribute to
      the inhibition of RNA trafficking in taiep oligodendrocytes.

PMID- 14697660
TI  - NCAM180 and glutamate receptor subtypes in potentiated spine synapses: an
      immunogold electron microscopic study.
AB  - Activity-dependent changes in expression and localization of the largest major
      isoform of the neural cell adhesion molecule NCAM180 and three subtypes of
      glutamate receptors predominantly expressed in the outer part of the molecular
      layer of the dentate gyrus of adult rats-the NMDA receptor NR2A, the AMPA
      receptor GluR2/3, and the metabotropic glutamate receptor mGluR1 - were
      investigated using postembedding immunogold labeling, and electron microscopy. In
      synaptic membranes of nonstimulated spine synapses, NCAM180 and NR2A accumulated
      in the center of the postsynaptic density, whereas GluR2/3 and mGluR1 were
      distributed evenly. Twenty-four hours following induction of long-term
      potentiation in vivo, NCAM180 and NR2A accumulated at the edges of postsynaptic
      densities, whereas GluR2/3 was localized more centrally. Also, the distribution
      of gold particles per synapse significantly changed for NCAM180, NR2A, and
      mGluR1. Thus, changes in synaptic strength are associated with concomitant
      changes in the expression and distribution of NCAM180 and glutamate receptors,
      particularly of the NR2A subtype.

PMID- 14697661
TI  - Regulation of RPTPbeta/phosphacan expression and glycosaminoglycan epitopes in
      injured brain and cytokine-treated glia.
AB  - Several chondroitin sulfate proteoglycans (CSPGs) are upregulated after CNS
      injury and are thought to limit axonal regeneration in the adult mammalian CNS.
      Therefore, we examined the expression of the CSPG, receptor protein tyrosine
      phosphatase beta (RPTPbeta)/phosphacan, after a knife lesion to the cerebral
      cortex and after treatment of glial cultures with regulatory factors. The three
      splice variants of this CSPG gene, the secreted isoform, phosphacan, and the two
      transmembrane isoforms, the long and short RPTPbeta, were examined. Western blot
      and immunostaining analysis of injured and uninjured tissue revealed a transient
      decrease of phosphacan protein levels, but not of short RPTPbeta, in the injured
      tissue from 1 to 7 days postlesion (dpl). By real time RT-PCR, we show that
      phosphacan and long RPTPbeta mRNA levels are transiently down-regulated at 2 dpl,
      unlike those of short RPTPbeta which increased after 4 dpl. In contrast to the
      core glycoprotein, the phosphacan chondroitin sulfate (CS) glycosaminoglycan
      epitope DSD-1 was up-regulated after 7 dpl. Phosphacan was expressed by
      cultivated astrocytes and oligodendrocyte precursors but was more glycanated in
      oligodendrocyte precursors, which produce more of DSD-1 epitope than astrocytes.
      Epidermal growth factor/transforming growth factor alpha strongly increased the
      astrocytic expression of long RPTPbeta and phosphacan and slightly the short
      RPTPbeta protein levels, while interferon gamma and tumor necrosis factor alpha
      reduced astrocytic levels of phosphacan, but not of the receptor forms. Examining
      the effects of phosphacan on axon growth from rat E17 cortical neurons, we found
      that phosphacan stimulates outgrowth in a largely CS dependent manner, while it
      blocks the outgrowth-promoting effects of laminin through an interaction that is
      not affected by removal of the CS chains. These results demonstrate complex
      injury-induced modifications in phosphacan expression and glycanation that may
      well influence axonal regeneration and repair processes in the damaged CNS.

PMID- 14697662
TI  - The anterogradely transported BDNF promotes retinal axon remodeling during eye
      specific segregation within the LGN.
AB  - Neurotrophins have been implicated in regulating many aspects of neuronal
      development and plasticity, including dendritic and axonal elaboration, by acting
      primarily as target derived trophic factors. Recently, we have shown that brain
      derived neurotrophic factor (BDNF) is produced by retinal ganglion cells (RGCs)
      and travels in an anterograde direction along the optic nerve in neonatal rats.
      Here, we have assessed whether the anterogradely transported BDNF plays a role in
      shaping the retinogeniculate connectivity during development. We used intraocular
      injections of antisense oligonucleotides to suppress selectively retinal
      synthesis and anterograde transport of BDNF in rat pups. We found that in the
      absence of endogenous BDNF, RGC axons retract from their target in the dorsal
      lateral geniculate nucleus (dLGN). The blockade of BDNF action at the retinal
      level with the tyrosine kinase inhibitor, K252a, failed to produce this effect,
      suggesting an anterograde action of the endogenous BDNF. Moreover, the effects of
      BDNF removal on RGC fibers were evident only during a narrow temporal window
      coincident with the critical period for the retinothalamic refinement, indicating
      a role for BDNF on growth and elaboration of RGC axons rather than on their
      maintenance. Altogether these results propose a novel role for BDNF in the
      elaboration of retinogeniculate axons.

PMID- 14697663
TI  - EphA/ephrin-A interactions regulate epileptogenesis and activity-dependent axonal
      sprouting in adult rats.
AB  - The Eph family of tyrosine kinase receptors and their ligands, ephrins, are
      distributed in gradients and serve as molecular guidance cues for axonal
      patterning during neuronal development. Most of these molecules are also
      expressed in mature brain. Thus, we examine here the potential roles of such
      molecules in plasticity and activity-dependent mossy fiber sprouting of adult
      CNS. We show that the ligand ephrin-A3 and the receptor EphA5 are expressed in
      complementary gradients in the adult rat mossy fiber system. Using the kindling
      model, we demonstrate that exogenous immunoadhesins that affect the interaction
      of endogenous EphA receptors and ephrin-A ligands modulate the development of
      kindling, one type of long-term plasticity, in mature rat brain. These
      immunoadhesins, combined with epileptogenic stimulations, alter both the extent
      and the pattern of collateral axonal sprouting in the mossy fiber pathway. Our
      results suggest that EphA receptors and ephrin-A ligands modify neuronal
      plasticity and may serve as spatial cues that modulate the development and
      pattern of activation-dependent axonal growth in adult CNS.

PMID- 14697664
TI  - Targeting the EphA4 receptor in the nervous system with biologically active
      peptides.
AB  - EphA4 is a member of the Eph family of receptor tyrosine kinases and has
      important functions in the developing and adult nervous system. In the adult,
      EphA4 is enriched in the hippocampus and cortex, two brain structures critical
      for learning and memory. To identify reagents that can discriminate between the
      many Eph receptors and selectively target EphA4, we used a phage display
      approach. We identified three 12-amino acid peptides that preferentially bind to
      EphA4. Despite lack of a common sequence motif, these peptides compete with each
      other for binding to EphA4 and antagonize ephrin binding and EphA4 activation at
      micromolar concentrations, indicating that they bind with high affinity to the
      ephrin-binding site. Furthermore, one of the peptides perturbs the segmental
      migration of EphA4-positive neural crest cells in chick trunk organotypic
      explants. Hence, this peptide can disrupt the physiological function of
      endogenous EphA4 in situ. We also identified additional peptides that bind to
      EphA5 and EphA7, two other receptors expressed in the nervous system. This panel
      of peptides may lead to the development of pharmaceuticals that differentially
      target Eph receptors to modulate neuronal function in specific regions of the
      nervous system.

PMID- 14697665
TI  - Selective and persistent activation of extracellular signal-regulated protein
      kinase by nitric oxide in glial cells induces neuronal degeneration in
      glutathione-depleted midbrain cultures.
AB  - Intracellular glutathione (GSH) levels determine whether nitric oxide (NO) is
      neurotrophic for dopamine neurons or triggers a cell death cascade in primary
      midbrain cultures. We have investigated herein the role of the extracellular
      signal regulated protein kinase (ERK) 1/2 pathway in this GSH switching effect.
      The short-lived NO donor DEA/NO induces a transient activation of ERK-1/2 that
      totally disappears 2 h after NO administration. The depletion of GSH increases
      and the supplementation of GSH suppresses ERK-1/2 activation in response to NO
      treatment. More interestingly, GSH depletion changes the kinetic of
      phosphorylation leading to a second prolonged phase of ERK-1/2 activation from 2
      to 16 h after NO addition. This change of kinetic is ultimately responsible for
      NO toxicity under GSH-depleted conditions, because selective blockade of the
      second and persistent phase of activation prevents cell death. In addition, the
      only transient ERK activation, induced by NO under normal GSH conditions, did not
      cause ERK-dependent cell death. Immunocytochemical colocalization studies
      demonstrate that ERK activation takes place exclusively in glial cells, mainly in
      astrocytes and less frequently in oligodendrocytes and glial progenitors.
      Furthermore, glial cell elimination or inactivation in the culture, by gliotoxic
      drugs, abrogates NO-induced ERK activation. Our results indicate that
      neurotrophism of NO switches into neurotoxicity after GSH depletion due to
      persistent activation of the ERK-1/2 signaling pathway in glial cells. The
      implication of these results in pathological conditions like Parkinson's disease,
      where GSH depletion and NO overproduction have been documented, are discussed.

PMID- 14697666
TI  - Glutamate excitotoxicity attenuates insulin-like growth factor-I prosurvival
      signaling.
AB  - Recent evidence suggests that impaired insulin/insulin-like growth factor I (IGF
      I) input may be associated to neurodegeneration. Several major neurodegenerative
      diseases involve excitotoxic cell injury whereby excess glutamate signaling leads
      to neuronal death. Recently it was shown that glutamate inactivates Akt, a serine
      kinase crucially involved in the prosurvival actions of IGF-I. We now report that
      excitotoxic doses of glutamate antagonize Akt activation by IGF-I and inhibit the
      neuroprotective effects of this growth factor on cultured neurons. Glutamate
      induces loss of sensitivity to IGF-I by phosphorylating the IGF-I receptor
      docking protein insulin-receptor-substrate (IRS)-1 in Ser(307) through a pathway
      involving activation of PKA and PKC in a hierarchical fashion. Administration of
      Ro320432, a selective PKC inhibitor, abrogates the inhibitory effects of
      glutamate on IGF-I-induced Akt activation in vitro and in vivo and is sufficient
      to block the neurotoxic action of glutamate on cultured neurons. Notably,
      administration of Ro320432 after ischemic insult, a major form of excitotoxic
      injury in vivo, results in a marked decrease ( approximately 50%) in infarct
      size. Therefore, uncoupling of IGF-I signaling by glutamate may constitute an
      additional route contributing to excitotoxic neuronal injury. Further work should
      determine the potential use of PKC inhibitors as a novel therapeutic strategy in
      ischemia and other excitotoxic insults.

PMID- 14697667
TI  - Rb binding protein Che-1 interacts with Tau in cerebellar granule neurons.
      Modulation during neuronal apoptosis.
AB  - Che-1 is a recently identified human Rb binding protein that inhibits the Rb
      growth-suppressing function and regulates cell proliferation. Che-1 contacts the
      Rb and competes with HDAC1 for Rb-binding site, removing HDAC1 from the Rb/E2F
      cell cycle-regulated promoters. We have investigated the expression of Che-1 in
      neuronal cells and we showed that Che-1 directly interacts with Tau. Tau is a
      microtubule-associated protein involved in the assembly and stabilization of
      neuronal microtubules network that plays a crucial role modulating neuronal
      morphogenesis, axonal shape, and transport. In rat cerebellar granule neurons
      (CGNs) Che-1 partially colocalizes with Tau in the cytoplasm. Che-1 binds the
      amino-terminal region of Tau protein, which is not involved in microtubule
      interactions. Tau and Che-1 endogenous proteins coimmunoprecipitate from CGNs
      cellular lysates. In addition, Che-1/Tau interaction was demonstrated both in
      overexpressing COS-7 cells and CGNs by FRET analysis. Finally, we observed that
      Tau/Che-1 interaction is modulated during neuronal apoptosis.

PMID- 14697668
TI  - Profiling of genes expressed by PTEN haploinsufficient neural precursor cells.
AB  - PTEN is a lipid phosphatase, and PTEN mutations are associated with gliomas,
      macrocephaly, and mental deficiencies. We have used PTEN +/- and PTEN +/+ mice to
      prepare subventricular zone (SVZ) precursor cells. Using DNA microarrays, we
      compared the expression profiles of PTEN +/+ and PTEN +/- cells and identified 91
      differentially expressed genes in PTEN +/- precursor cells. Many of the PTEN
      regulated genes are involved with signaling, cytoskeleton, extracellular matrix,
      metabolism, and transcription factors. Some of these changes are likely mediated
      by the transcription factor, HIF-1. We confirmed a subset of these changes by
      real-time PCR. In addition, we examined protein levels for two of the PTEN-up
      regulated genes, vascular endothelial growth factor (VEGF) and doublecortin
      (DCX). PTEN haploinsufficiency increases immunostaining for VEGF for both
      cultured precursor cells and sections of the SVZ. PTEN haploinsufficiency shifted
      most of the DCX-positive cells from the SVZ to the olfactory bulb. These
      observations indicate that even a small decrease in PTEN levels results in
      substantial changes in gene expression and precursor cell function.

PMID- 14697669
TI  - N-terminal alpha-dystroglycan binds to different extracellular matrix molecules
      expressed in regenerating peripheral nerves in a protein-mediated manner and
      promotes neurite extension of PC12 cells.
AB  - alpha-dystroglycan is a cell surface receptor that is expressed in many tissues
      including the nervous system. The study shows that a recombinant, non
      glycosylated N-terminal fragment of alpha-dystroglycan comprising residues 30 to
      315 [alphaDG (30-315)] bound to laminin-2/-4 and laminin-1, fibronectin and
      fibrinogen, all molecules highly upregulated in the regenerating peripheral
      nerve. The interaction was concentration dependent and saturable and could not be
      inhibited by heparin suggesting only minor involvement of sulfated carbohydrate
      moieties. In contrast to published data, addition of bivalent cations increased
      the binding affinity by only ten fold.alphaDG (30-315) promotes neurite extension
      of PC12 cells in a similar amount as described for laminin isoforms and could be
      inhibited in a concentration dependent manner by alphaDG (30-315) itself, soluble
      laminin-1, partially by heparin, EDTA, and an RGD-peptide. Furthermore, co
      immunoprecipitations between alpha-dystroglycan and beta1-integrin from PC12 cell
      surfaces suggested complex interactions between neuronal dystroglycan, integrins,
      and the ECM that induce neurite extension in vitro.

PMID- 14697670
TI  - Intraventricular transplantation of neural precursor cell spheres attenuates
      acute experimental allergic encephalomyelitis.
AB  - Brain transplantation of neural precursor cells (NPCs) has been proposed to
      enhance CNS regeneration. As the pathogenesis of most acute CNS diseases involves
      an inflammatory component, we studied whether NPC transplantation affects brain
      inflammation. Newborn rat multipotential NPCs were transplanted intraventriculary
      into acute experimental allergic encephalomyelitis (EAE) rats, a model for
      disseminated brain inflammation. Cells migrated into inflamed white matter and
      differentiated into glial cells. NPC transplantation attenuated the clinical
      severity of EAE and the brain inflammation, indicated by reduction in
      perivascular infiltrates and decreased expression of ICAM-1 and LFA-1. NPCs
      inhibited basal proliferation and proliferative responses to Concavalin-A and to
      MOG peptide of EAE rat-derived lymphocytes in vitro. Purified astrocytes
      inhibited lymphocyte proliferation in vitro, but did not migrate into EAE brains
      in vivo, and did not reduce EAE severity or brain inflammation. Thus,
      transplanted NPCs attenuate acute EAE via an anti-inflammatory mechanism which
      depends on cell ability to migrate into inflamed brain tissue.

PMID- 14697671
TI  - Nogo-A expression in the intact and injured nervous system.
AB  - The expression of Nogo-A mRNA and protein in the nervous system of adult rats and
      cultured neurons was studied by in situ hybridisation and immunohistochemistry.
      Nogo-A mRNA was expressed by many cells in unoperated animals, including spinal
      motor, DRG, and sympathetic neurons, retinal ganglion cells, and neocortical,
      hippocampal, and Purkinje neurons. Nogo-A protein was strongly expressed by
      presumptive oligodendrocytes, but not by NG2+glia and was abundant in motor, DRG,
      and sympathetic neurons, retinal ganglion cells, and many Purkinje cells, but was
      difficult to detect in dentate gyrus neurons and some neocortical neurons.
      Cultured fetal mouse neocortical neurons and adult rat DRG neurons strongly
      expressed Nogo-A in their perikarya, growth cones, and axonal varicosities. All
      axons in the intact sciatic nerve contained Nogo-A and many but not all
      regenerating axons were strongly Nogo-A immunopositive after sciatic nerve
      transection. Ectopic muscle fibres that developed among the regenerating axons
      were also Nogo-A immunopositive. Following injury to the spinal cord, Nogo-A mRNA
      was upregulated around the lesion and Nogo-A protein was strongly expressed in
      injured dorsal column fibres and their sprouts which entered the lesion site.
      Following optic nerve crush, Nogo-A accumulated in the proximal and distal stumps
      bordering the lesions.

PMID- 14697672
TI  - Calcium-dependent mitochondrial superoxide modulates nuclear CREB phosphorylation
      in hippocampal neurons.
AB  - We report evidence that mitochondrially produced superoxide (O(2)(-)) is involved
      in signaling in hippocampal neurons by examining the relationship between strong
      but physiological increases in cytosolic free Ca(2+), mitochondrial calcium
      accumulation, O(2)(-) production, and CREB phosphorylation. Strong depolarization
      induced Ca(2+) entry through NMDA or L-type Ca(2+) channels evoked large Ca(2+)
      transients, a sustained increase in O(2)(-), and a large rise in nuclear CaM and
      pCREB. Under these conditions, inhibition of mitochondrial Ca(2+) uptake and
      consequent O(2)(-) production suppressed Ca(2+) entry-induced pCREB elevation,
      indicating that O(2)(-) produced by mitochondria supports CREB phosphorylation.
      Similarly, inhibiting mitochondrial respiration blocked O(2)(-) production and
      also depressed the elevation of pCREB. Blocking calcineurin reversed this
      depression. We conclude that strong Ca(2+) entry promotes mitochondrial calcium
      accumulation and the subsequent enhancement of mitochondrial O(2)(-) production,
      which in turn prolongs the lifetime of pCREB by suppressing calcineurin-dependent
      pCREB dephosphorylation.

PMID- 14697673
TI  - Constitutive EGFR signaling confers a motile phenotype to neural stem cells.
AB  - The epidermal growth factor receptor (EGFR) has been shown to play an important
      role in brain development, including stem and precursor cell survival,
      proliferation, differentiation, and migration. To further examine the temporal
      and spatial requirements of erbB signals in uncommitted neural stem cells (NSCs),
      we expressed the ligand-independent EGF receptor, EGFRvIII, in C17.2 NSCs. These
      NSCs are known to migrate and to evince a tropic response to neurodegenerative
      environments in vivo but for which an underlying mechanism remains unclear. We
      show that enhanced erbB signaling via constitutive kinase activity of EGFRvIII in
      NSCs sustains an immature phenotype and enhances NSC migration.

PMID- 14697674
TI  - Cell surface trafficking of the antidepressant-sensitive norepinephrine
      transporter revealed with an ectodomain antibody.
AB  - The antidepressant-sensitive L-norepinephrine (NE) transporter (NET;SLC6A2) is a
      critical determinant of neurotransmitter inactivation following NE release at
      synapses. Although regulated trafficking of NET has been documented in
      transfected cells, a lack of reagents suitable for reporting native NET surface
      exposition has limited validation of this concept in neurons. In the current
      report, we document the utility of a novel antibody (43408) directed at conserved
      sequences in the NET second extracellular loop. Using human NET (hNET) stably
      transfected cells, we document loss of NET surface expression following acute (30
      min) phorbol ester treatments. In superior cervical ganglion (SCG) cultures, NET
      surface expression is prominent on varicosities defined by FM1-43 labeling of
      living neurons or synaptophysin labeling of fixed preparations. Moreover, NET
      surface density can be rapidly augmented by brief depolarization (5 min, 40 mM
      K(+)). Similarly, in brainstem cultures, we demonstrate an increase in NET
      surface labeling following either depolarization or angiotensin II stimulation.
      These findings provide the first evidence for regulated trafficking of NET in
      neurons and support the suggestion that activity-dependent NET trafficking may
      provide additional modulatory capacity for noradrenergic signaling.

PMID- 14697675
TI  - Nitric-oxide-induced depolarization of neuronal mitochondria: implications for
      neuronal cell death.
AB  - Nitric oxide (NO(*)) has known toxic effects on central nervous system neurons.
      This study characterized the effect of NO(*) on mitochondrial membrane changes by
      exploring the relationship among NO(*), excitatory receptor activation, and the
      induction of peroxynitrite, a highly toxic NO(*) reactant, to neuronal injury.
      Cultured rat cortical neurons were exposed to the NO(*) generator,
      diethylenetriamine/nitric oxide adduct, and were examined for signs of cell
      death, mitochondrial membrane potential changes (Deltapsi(m)), and the induction
      of a mitochondrial permeability transition (MPT). Neurons were also examined for
      nitrotyrosine (NT) immunoreactivity, a marker of reactive nitrogen species (RNS)
      formation. Neurons exposed to NO(*) or to N-methyl-D-aspartate (NMDA) exhibited
      similar rapid depolarization of mitochondria, which was prevented by an NMDA
      receptor antagonist. Electrophysiological studies demonstrated NO(*) potentiation
      of NMDA-induced NMDA receptor currents. NO(*) and NMDA-treated neurons had
      evidence of mitochondrial-specific NT immunoreactivity that was prevented by a
      SOD/catalase mimetic (EUK-134). EUK-134 treatment reduced both NO(*) and NMDA
      induced NT formation and neuronal cell death. EUK-134 did not prevent NO-induced
      Deltapsi(m) but partially prevented NMDA-induced Deltapsi(m) loss. Although NO(*)
      and NMDA both induced MPT and MPT inhibitors prevented NO-induced Deltapsi(m),
      they did not result in significant neuroprotection, in contrast to treatment
      designed to decrease peroxynitrite formation. These data suggest that NO-induced
      NMDA receptor activation is closely linked to intramitochondrial NO
      peroxynitrite/RNS formation and thereby acts as a major mediator of neuronal cell
      death.

PMID- 14697676
TI  - LPA1 receptor-deficient mice have phenotypic changes observed in psychiatric
      disease.
AB  - Several psychiatric diseases, including schizophrenia, are thought to have a
      developmental aetiology, but to date no clear link has been made between
      psychiatric disease and a specific developmental process. LPA(1) is a G(i)
      coupled seven transmembrane receptor with high affinity for lysophosphatidic
      acid. Although LPA(1) is expressed in several peripheral tissues, in the nervous
      system it shows relatively restricted temporal expression to neuroepithelia
      during CNS development and to myelinating glia in the adult. We report the
      detailed neurological and behavioural analysis of mice homozygous for a targeted
      deletion at the lpa(1) locus. Our observations reveal a marked deficit in
      prepulse inhibition, widespread changes in the levels and turnover of the
      neurotransmitter 5-HT, a brain region-specific alteration in levels of amino
      acids, and a craniofacial dysmorphism in these mice. We suggest that the loss of
      LPA(1) receptor generates defects resembling those found in psychiatric disease.

PMID- 14697677
TI  - Targeting of recombinant agrin to axonal growth cones.
AB  - Targeting of proteins to specific subcellular locations within pre- and
      postsynaptic neurons is essential for synapse formation. The heparan sulfate
      proteoglycan agrin orchestrates postsynaptic differentiation of the neuromuscular
      junction and may be involved in synaptic development and signaling in the central
      nervous system (CNS). Agrin is expressed as transmembrane and secretory isoforms
      with distinct N-termini. We examined the distribution of recombinant agrin in
      cultured motor and hippocampal neurons by transfection with agrin-GFP constructs.
      Immunostaining revealed a vesicular transport compartment within all neurites.
      Plasma membrane insertion and secretion of recombinant agrin were targeted to
      axonal growth cones of motor neurons; transmembrane agrin-GFP was targeted
      predominantly to axons and axonal growth cones in hippocampal neurons. We used
      agrin deletion mutants to show that axonal targeting of agrin depends on multiple
      domains that function in an additive fashion, including the very N-terminal
      portions and the C-terminal half of the molecule.

PMID- 14697678
TI  - Cell death in cartilage.

PMID- 14697679
TI  - Increased presence of cells with multiple elongated processes in osteoarthritic
      femoral head cartilage.
AB  - OBJECTIVE: This study examined the morphology of chondrocytes in articular
      cartilage from osteoarthritic (OA) and non-OA human femoral heads and in
      particular the appearance of a sub-population of cells with multiple elongated
      processes radiating up to 30 microm into the extracellular matrix. METHODS:
      Cartilage explants were removed from 8 anatomical sites over the surface of OA
      (n=6) and non-OA (n=5) femoral heads. Cells were labeled for vimentin
      intermediate filaments and visualized using epi-fluorescence and confocal
      microscopy. The percentage of cells with elongated processes was correlated with
      macroscopic and histological indicators of osteoarthritis. RESULTS: Cells with
      processes accounted for less than 10% of the total cell population in non-OA
      cartilage. By contrast, in the peripheral regions of the OA femoral head these
      cells accounted for 20-45% of the total cell population, the differences being
      statistically significant. These peripheral areas are habitually non-load bearing
      and were also the most likely to show gross fibrillation and pannus formation. A
      statistically significant correlation was demonstrated between the percentage of
      cells with processes and the histological extent of the OA degradation,
      quantified in terms of the Mankin score. CONCLUSIONS: The extension of cell
      processes, which may be associated with localized breakdown of the pericellular
      matrix, will undoubtedly alter numerous aspects of cell function including
      phenotypic expression and mechanotransduction. Hence these significant changes in
      chondrocyte morphology are likely to have important implications for the
      aetiology of osteoarthritis and the development of potential treatment
      strategies.

PMID- 14697680
TI  - Establishment of a bipotent cell line CL-1 which differentiates into chondrocytes
      and adipocytes from adult mouse.
AB  - OBJECTIVE: Establishment of a clonal bipotent chondroprogenitor cell line from
      adult mouse to provide a new tool for the elucidation of chondrogenesis in adult
      animal. DESIGN: A clonal cell line CL-1 was established from tibia of adult
      mouse. Differentiation of CL-1 was characterized in monolayer culture. Effects of
      growth factors (TGF-beta(1), IGF-I, bFGF) and hormones (all trans retinoic acid,
      1 alpha.25(OH)(2)D(3), PTH (1-34)) on the growth and differentiation of CL-1 were
      examined. Bipotency of CL-1 in vivo was examined by transplantation into SCID
      mice. RESULTS: CL-1 formed alcian blue (pH1.0) positive nodules spontaneously.
      The nodules were mineralized in the presence of ascorbic acid and beta
      glycerophosphate. CL-1 differentiated also into oil red O positive adipocytes
      spontaneously. CL-1 cells expressed specific genes of chondrocytes (collagen type
      II, X, aggrecan) and adipocytes (PPAR-gamma(2), aP(2)). Hyaline cartilage and
      adipose tissue formation was observed also in subcutaneously transplanted CL-1
      cells into SCID mice. These data demonstrate that CL-1 has bipotency either in
      vitro or in vivo. TGF-beta(1)suppressed growth of CL-1 and induced dominant
      chondrogenesis accompanied with marked suppression of adipogenesis in 10% FCS.
      IGF-I stimulated both growth (in 3% FCS) and differentiation of CL-1 into both
      lineages (in 10% FCS). 1 alpha.25(OH)(2)D(3)and all trans retinoic acid acted as
      negative regulators on proliferation and differentiation of CL-1 in 10% FCS.
      CONCLUSIONS: CL-1 will be a useful tool for the understanding of chondrogenesis
      in adult animal. Furthermore, CL-1 can be also a powerful tool for screening of
      the chondrogenic agent.

PMID- 14697681
TI  - Characterization of cells from pannus-like tissue over articular cartilage of
      advanced osteoarthritis.
AB  - OBJECTIVE: To identify the characteristics of cells isolated from pannus-like
      soft tissue on osteoarthritic cartilage (OA pannus cells), and to evaluate the
      role of this tissue in osteoarthritis (OA). METHODS: OA pannus cells were
      isolated from pannus-like tissues in five joints obtained during arthroplasty.
      The phenotypic features of the isolated cells were characterized by safranin-O
      staining and immunohistochemical studies. Expression of MMP-1, MMP-3 and MMP-13
      was also assessed using reverse transcriptase-polymerase chain reactions (RT
      PCR), enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry. RESULTS:
      Foci and plaque formation of pannus-like tissue over cartilage surface were found
      in 15 of 21 (71.4%) OA joints macroscopically, and among them, only five samples
      had enough tissue to be isolated. OA pannus cells were positive for type I
      collagen and vimentin, besides they also expressed type II collagen and aggrecan
      mRNA. Spontaneous expression of MMP-1, MMP-3 and MMP-13 was detected in OA pannus
      cells. Similar or higher levels of MMPs were detected in the supernatant of
      cultured OA pannus cells compared to OA chondrocytes, and among these MMP-3
      levels were relatively higher in OA pannus cells. Immunohistochemically, MMP-3
      positive cells located preferentially in pannus-like tissue on the border of
      original hyaline cartilage. CONCLUSION: Our results showed that OA pannus cells
      shared the property of mesenchymal cells and chondrocytes; however, their origin
      seemed different from chondrocytes or synoviocytes. The spontaneous expression of
      MMPs suggests that they are involved in the articular degradation in OA.

PMID- 14697682
TI  - Laterally elevated wedged insoles in the treatment of medial knee osteoarthritis.
      A two-year prospective randomized controlled study.
AB  - OBJECTIVE: To compare the clinical effects of laterally wedged insoles and
      neutrally wedged insoles (used as control) in patients with medial femoro-tibial
      knee osteoarthritis. METHODS:  STUDY DESIGN: 24-month prospective randomized
      controlled study. PATIENTS: Outpatients with painful medial femoro-tibial knee
      osteoarthritis. OUTCOME MEASURES: Patient's overall assessment of disease
      activity (5 grade scale), WOMAC index subscales and concomitant treatments.
      STATISTICAL ANALYSIS: Performed as an intention-to-treat analysis, with the last
      observation carried forward (LOCF). Main symptomatic criterion: Improvement in
      the patient's assessment of activity (defined as a reduction of one grade or more
      at the end of the study as compared to baseline, and no intra-articular injection
      or lavage during the 6 months previous to the last visit). Secondary criteria for
      assessment: (a) Changes in the WOMAC subscales at month 24, and (b) concomitant
      therapies (analgesics, NSAIDs and intra-articular injections or lavages).
      Structural criterion: Joint space width (JSW) at the narrowest point. Non
      compliance was defined as intermittent or lack of insole fitting at two
      consecutive visits. Compliance within groups was compared by using a life table
      analysis technique (Log-Rank). RESULTS: The baseline characteristics of the 156
      recruited patients (41 males, 115 females, mean age 64.8 years) were not
      different in the 2 treatment groups. At year 2, there was no statistically
      significant difference between the 2 groups concerning the percentages of
      patients with improvement in both global assessment of disease activity and in
      WOMAC subscales (pain, stiffness, function). The number of days with NSAIDs
      intake was lower in the group with laterally wedged insoles than in the neutrally
      wedged group (71+/-173 days vs. 127+/-193 days, P=0.003, Mann-Whitney test). The
      mean joint space narrowing rate did not differ between the two groups: 0.21+/
      0.59 mm/year in the laterally wedged group vs 0.12+/-0.32 mm/year in the
      neutrally wedged group. Compliance and tolerance were satisfactory. Compliance
      was different between the 2 groups at month 24, with a greater frequency of
      patients who wore insoles permanently in the laterally wedged insole group than
      in the other group (85.8% vs 71.9%, P=0.023). CONCLUSION: This study failed to
      demonstrate a relevant symptomatic and/or structural effect of laterally-wedged
      insoles in medial femoro-tibial OA. However, the reduced NSAIDs intake and the
      better compliance in the treatment group are in favor of a beneficial effect of
      laterally-wedged insoles in medial femoro-tibial OA.

PMID- 14697683
TI  - Chondrocytes attach to hyaline or calcified cartilage and bone.
AB  - OBJECTIVE: The initial attachment of transplanted chondrocytes to the surface of
      a cartilage defect is crucial for the success of chondrocyte transplantation. The
      purpose of this study was to investigate the early interaction of chondrocytes
      with the deep or calcified zones of cartilage or the subchondral bone, joint
      surfaces to which transplanted chondrocytes might have to attach in vivo. DESIGN:
      Freshly isolated (primary) or passaged (P1) chondrocytes were seeded on the top
      of bone plugs having either a surface composed of mid-deep zone hyaline cartilage
      or calcified cartilage or bone only. The percent of cells that attached, the role
      of integrins in cell attachment, and gene expression after placement of the cells
      on the different surfaces were determined. RESULTS: Both primary and passaged
      chondrocytes attached efficiently to all three surfaces (over 88% of seeded
      cells). The chondrocytes showed a punctate distribution of beta 1-integrin and
      vinculin, which in areas co-localized with actin, suggesting that the cells
      formed focal adhesions. The primary chondrocytes had a different shape,
      appearance of focal contacts, and actin distribution when compared to passaged
      cells and these did not appear to be influenced by the type of surface to which
      the cells attached. Blocking either beta 1-integrin or alpha v beta 5 integrin
      partially inhibited (between 27 to 48% and 26 to 37% respectively) attachment of
      both primary and passaged chondrocytes to all surfaces. Blocking alpha v beta 3
      had no effect on adhesion. There was expression of type II collagen and aggrecan
      core protein mRNA by 2h. The different surfaces did not appear to affect the
      expression of these genes up to 24h although gene levels were lower in passaged
      cells. CONCLUSIONS: Chondrocytes, either freshly isolated or passaged, have the
      potential to adhere to the different joint surfaces that could be exposed in a
      cartilage defect. Understanding how chondrocytes adhere and interact with damaged
      joint surfaces may help identify methods to enhance the retention of transplanted
      cells in the defect site and cartilage tissue formation.

PMID- 14697684
TI  - Mechanical response of bovine articular cartilage under dynamic unconfined
      compression loading at physiological stress levels.
AB  - OBJECTIVE: The objective of this study was to characterize the dynamic modulus
      and compressive strain magnitudes of bovine articular cartilage at physiological
      compressive stress levels and loading frequencies. DESIGN: Twelve distal femoral
      cartilage plugs (3mm in diameter) were loaded in a custom apparatus under load
      control, with a load amplitude up to 40 N and loading frequencies of 0.1, 1, 10
      and 40 Hz, resulting in peak Cauchy stress amplitudes of 4.8 MPa (engineering
      stress 5.7 MPa). RESULTS: The equilibrium Young's modulus under a tare load of
      0.4N was 0.49+/-0.10 MPa. In the limit of zero applied stress, the incremental
      dynamic modulus derived from the slope of the stress-strain curve increased from
      14.6+/-6.9 MPa at 0.1 Hz to 28.7+/-7.8 MPa at 40 Hz. At 4 MPa of applied stress,
      the corresponding increase was from 48.2+/-13.5 MPa at 0.1 Hz to 64.8+/-13.0 MPa
      at 40 Hz. Peak compressive strain amplitudes varied from 15.8+/-3.4% at 0.1 Hz to
      8.7+/-1.8% at 40 Hz. The phase angle decreased from 28.8 degrees +/-6.7 degrees
      at 0.1 Hz to-0.5 degrees +/-3.8 degrees at 40 Hz. DISCUSSION: These results are
      representative of the functional properties of articular cartilage under
      physiological load magnitudes and frequencies. The viscoelasticity and
      nonlinearity of the tissue helps to maintain the compressive strains below 20%
      under the physiological compressive stresses achieved in this study. These
      findings have implications for our understanding of cartilage metabolism and
      chondrocyte viability under various loading regimes. They also help establish
      guidelines for cartilage functional tissue engineering studies.

PMID- 14697685
TI  - Distribution of Endo180 receptor and ligand in developing articular cartilage.
AB  - OBJECTIVE: To investigate the expression of a novel member of the mannose
      receptor family, Endo180 (also known as uPARAP), and the distribution of Endo180
      ligand(s) in the articular cartilage and growth plate of normal CBA mice and
      STR/ort mice, a well characterized model of spontaneous osteoarthritis. DESIGN: A
      polyclonal anti-Endo180 antibody was used to determine receptor expression. The
      Endo180 extracellular domain fused to a human immunoglobulin Fc tail was used to
      detect ligand. RESULTS: Endo180 receptor was strongly expressed in chondrocytes
      both in vitro and throughout the articular cartilage of young CBA and STR/ort
      mice. Expression decreased in older animals. In STR/ort mice with osteoarthritic
      lesions, no upregulation of Endo180 was detected. In the developing growth plate,
      Endo180 was expressed strongly by the proliferating chondrocytes. In contrast,
      Endo180 ligand was detected most strongly in hypertrophic zone of the growth
      plate and only at low levels in articular cartilage. In cultured chondrocytes,
      Endo180 was localized on the cell surface and in intracellular vesicles.
      CONCLUSION: Constitutively recycling endocytic receptors function to internalize
      ligand from the extracellular milieu and the ability of Endo180 to bind both
      glycosylated ligands and collagens suggests a role in extracellular matrix
      remodeling. Expression of Endo180 in articular cartilage chondrocytes of young,
      but not old, mice and the reciprocal expression of Endo180 and its ligands in the
      growth plate suggest that this receptor is involved in cartilage development but
      not in cartilage homeostasis. In addition, our data indicates that Endo180 does
      not appear to play a role in the development or progression of murine
      osteoarthritis.

PMID- 14697686
TI  - Adsorption of three azo reactive dyes by metal hydroxide sludge: effect of
      temperature, pH, and electrolytes.
AB  - Adsorption of azo reactive dyes by metal hydroxide sludge were investigated using
      CI Reactive Red 2 (RR-2), CI Reactive Red 120, (RR-120), and CI Reactive Red 141
      (RR-141). The adsorption isotherms, including the Langmuir constants (Q degrees
      and b) and the Freundlich constant (K(f)), for RR-2 decreased with increasing
      temperature, but this was reversed for RR-120 and RR-141. This behavior implied
      an exothermic process for RR-2 but an endothermic process for RR-120 and RR-141.
      The enthalpy value of adsorption for RR-2, RR-120, and RR-141 was -5.56, 2.77,
      and 6.41 kJ/mol, respectively, indicating that the adsorption of the less charged
      dyes (RR-2) was mainly physical, but that of the more charged dyes (RR-120 and RR
      141) was chemical. The optimum system pH of 8.6+/-0.3 was maintained even when
      the solution pH was varied from 3 to 10. Higher concentration or more valence of
      anions of electrolytes in dye solution caused decreasing dye adsorption
      efficiency of metal hydroxide sludge. A higher dosage of sludge is required for
      real textile wastewater (>1% w/v) than for the synthetic dye solution (0.2% w/v).
      The leachates of heavy metals from metal hydroxide sludge to the environment are
      very low, which are within the standard limit of industrial effluent and
      leachable substances.

PMID- 14697687
TI  - Aggregate formation in oil and adsorption at oil/water interface: thermodynamics
      and its application to the oleyl alcohol system.
AB  - The thermodynamic equations for examining aggregate formation in an oil phase and
      adsorption at the oil/water interface of a nonionic solute were derived. The
      total differentials of chemical potentials of species and the oil/water
      interfacial tension were expressed as functions of temperature, pressure, and the
      total concentration of solute in the oil phase after explicit consideration of
      aggregate formation. The partial derivatives of the chemical potentials and the
      interfacial tension with respect to the independent variables were found to
      provide the thermodynamic quantities of aggregate formation and adsorption from
      oil phase to the interface by introducing the concept of an ideally dilute
      associated solution. These equations were applied to the cyclohexane solution of
      oleyl alcohol/water system, and the adsorption and aggregate formation was
      examined.

PMID- 14697688
TI  - Shear-induced phase transitions in sucrose ester surfactant.
AB  - The behavior of a commercial sucrose stearate blend has been examined by means of
      various experimental techniques (differential scanning calorimetry, light
      polarization and electron microscopy, and rotational rheometry). A partial phase
      diagram in water has been established. It shows that the binary system forms a
      lamellar lyotropic mesophase and that the melting behavior is characterized by a
      lamellar gel-lamellar liquid crystalline phase transition. The identification of
      the liquid crystalline phase has been carried out from textural observation using
      polarization microscopy and freeze-fracture electron microscopy. At low
      surfactant concentrations, the phase transition has been followed through
      rheological experiments. Furthermore, a shear-induced transition, from the
      lamellar phase (sheets of surfactant bilayers including a few large multilamellar
      vesicles) to an onion phase, has been observed above a critical temperature of 43
      degrees C. The vesicles so obtained did not relax over more than 3 weeks. The
      presence of a small ratio of distearate in the sugar ester blend seems to be the
      key to vesicle formation at low surface-active material concentration.

PMID- 14697689
TI  - Characterization and determination of the thermodynamic and kinetic properties of
      the adsorption of the molybdenum(VI)-calmagite complex onto active carbon.
AB  - The extraction of the Mo(VI)-calmagite complex by adsorption onto active carbon
      is investigated in the present paper. Thermodynamic and kinetic properties and
      different adsorption isotherms were determined. The adsorption studies have shown
      that both the empirical Freundlich and the classical Langmuir isotherms
      successfully fit the experimental results. The overall adsorption process was
      exothermic and spontaneous in the temperature range from 283 to 323 K; namely,
      DeltaH(0) and DeltaS(0) values were found to be -8.15 kJ mol(-1) and -3.86 J mol(
      1) K, respectively. The high activation energy demanded for desorption of the
      Mo(VI)-calmagite complex surface indicated that the overall process was
      controlled by the slow desorption, while a fast and low activated adsorption of
      the complex onto active carbon surface was fairly favored. These features
      indicate that active carbon may be very useful for preconcentration of molybdenum
      from diluted solutions.

PMID- 14697690
TI  - Determination of acidic sites and binding toxic metal ions on cumin surface using
      nonideal competitive adsorption model.
AB  - A fundamental study of the application of cumin biomass in the recovery of Cu and
      Zn metal ion uptake from food and drinks is carried out at different pH's and at
      fixed ionic strength. The chemical characteristics of protein in cumin seeds were
      investigated. Results showed that cumin contains 18.25% crude protein, which
      includes 18 amino acids. The main reactive groups on protein cumin are amino and
      carboxylic groups of dicarboxylic amino acids, leading to a pH-dependent charge.
      Therefore, the cumin surface is considered as a heterogeneous system. To describe
      protonation behavior in a heterogeneous cumin biomass (cumin/0.1 M NaNO(3))
      system, acid-base titrations have been performed with conductometric and
      potentiometric titration. Measurement of the reactivity of cumin surface in the
      adsorption of Cu and Zn metal ions and determination of metal binding at
      different pH's were also carried out. To solve broad and ill-defined titration
      curves, a simplified version of nonideal competitive analysis (NICA) by Plette et
      al.) was applied. The results show that the sorption of the bivalent metal ions
      onto the whole surface of cumin could be attributed to a monodentate binding to
      one site mainly carboxylic-type site.

PMID- 14697691
TI  - Thermal and mechanical interfacial properties of the DGEBA/PMR-15 blend system.
AB  - In this work, the blend system of diglycidyl ether of bisphenol A and PMR-15
      polyimide is investigated in terms of thermal and dynamic mechanical interfacial
      properties of the casting specimens. The thermal stabilities are studied by
      thermogravimetric and thermomechanical analyses, and the dynamic mechanical
      properties are carried out by dynamic mechanical analysis. The results show that
      the thermal stabilities based on the initial decomposition temperature, the
      integral procedural decomposition temperature, and the glass transition
      temperature are increased with increasing PMR-15 content. The crosslinking
      density (rho) of the blend system is increased at 10 phr of PMR-15, compared with
      that of neat epoxy. Mechanical interfacial properties measured in the context of
      critical stress intensity factor and critical strain energy release rate show
      similar behaviors with E(a) and rho, probably due to the increase in
      intermolecular interactions or hydrogen bondings in polymer chains.

PMID- 14697692
TI  - A study of dilational rheological properties of polymers at interfaces.
AB  - Viscoelastic properties of two polymers, partially hydrolyzed polyacrylamide and
      partially hydrolyzed modified polyacrylamide, widely used in chemical flooding in
      the petroleum industry, were investigated at three interfaces, water-air, water
      dodecane, and water-crude oil, by means of a dilational method provided by I.T.
      Concept, France, at 85 degrees C. Polymer solutions were prepared in brine with
      10,000 mg/l sodium chloride and 2000 mg/l calcium chloride. It has been shown
      that the viscoelastic modulus increases with the increment of polymer
      concentration in the range of 0-1500 mg/l at the water-air interface. Each
      polymer shows different viscoelatic behavior at different interfaces. Generally
      speaking, values of the viscoelastic modulus (E), the real part (E'), and the
      imaginary part (E") at the crude oil-water interface for each polymer are lower
      than at the air-water or water-dodecane interface. The two polymers display
      different interfacial properties at the same interface. Polymer No. 2 gives more
      viscous interfaces than polymer No. 1. All the information obtained from this
      paper will be helpful in understanding the interfacial rheology of ultra-high
      molecular-weight polymer solutions.

PMID- 14697693
TI  - Preparation of a biodegradable matrix through polyion complex formation by mixing
      polylactide-based microspheres having oppositely charged surfaces.
AB  - The aggregation of polyions into microsphere (MS) complexes was studied as a
      preparative method for the construction of a biodegradable matrix. Aqueous
      suspensions of polylactide (PLA)-based MSs with positively and negatively charged
      surfaces, MS(K(3)(4+)-PLA) and MS(E(3)(4-)-PLA), respectively, immediately formed
      aggregates when mixed. The effects of the stoichiometry of the charged groups on
      the surfaces of the MSs and the ionic strength of the medium on aggregate
      formation, as well as the degradation behavior of the polyion complex (PIC)
      matrix over time, were investigated.

PMID- 14697694
TI  - Adsorption of egg albumin onto methylated yeast biomass.
AB  - A new biosorbent, methylated yeast (MeYE), was prepared for the adsorptive
      separation of proteins from aqueous solutions. Yeast was methylated in a 0.1 M
      HCl methyl alcohol solution at room temperature. About 80% of the carboxylic
      groups of yeast could be methylated within 9 h. The adsorption of egg albumin
      onto MeYE was studied to evaluate the protein adsorption ability of MeYE. At near
      neutral pH, egg albumin was scarcely adsorbed onto unmethylated yeast and the
      adsorbed amount of egg albumin increased with increasing methylation degree. The
      amount of egg albumin adsorbed onto MeYE increased with increasing pH from 4 to 7
      and steeply decreased above pH 7. The Langmuir isotherm was applied to determine
      the apparent adsorption constant and the saturated adsorbed amount of egg albumin
      on MeYE. Both the apparent adsorption constant and the saturated adsorbed amount
      increased with the degree of methylation. The saturated adsorbed amount of egg
      albumin onto MeYE having methylation degree 77% was 8.41 x 10(-6) mol g(-1) or
      0.378 gg(-1) at near neutral pH.

PMID- 14697695
TI  - Fourier transform surface-enhanced Raman scattering of single-layer nucleolipid
      Langmuir-Blodgett films on silver island film substrates.
AB  - Surface-enhanced Raman scattering (SERS) spectra of four amphiphilic nucleolipids
      in single-layer Langmuir-Blodgett (LB) films deposited on silver island film
      substrates from pure water and complementary nucleotide-containing subphase and
      corresponding powder normal Raman spectra were obtained. The analysis of these
      spectra indicates that the SERS effect is mainly caused by a charge-transfer
      mechanism, and only the nucleobase headgroup moieties and complementary bases
      combined with them through hydrogen bonds, which are directly in contact with the
      silver island film substrates, could be enhanced. For the amphiphilic
      nucleolipids with the identical nucleobase headgroups, the SERS spectra of the LB
      films are similar, implying that the orientations of these nucleobase moieties on
      the silver substrates are analogous. However, the nucleobase takes different
      orientations on the silver substrates before and after complementary binding. The
      nucleobases in the LB films deposited from pure water are nearly lying flat on
      the silver surface, while the complementary binding pairs transferred from the
      air/water interface tend to take an end-on orientation on the metal surface.

PMID- 14697696
TI  - Avidin self-associates with boric acid gel suspensions: an affinity boron carrier
      that might be developed for boron neutron-capture therapy.
AB  - It has been shown in preliminary studies that the antibacterial protein avidin
      self-associates with the boric acid gel polymer, and avidin-coated gel particles
      in the micrometer and submicrometer size ranges are of interest for boron neutron
      capture therapy (BNCT), which is neutron-induced fission of boron-10 to produce
      intense alpha radiation for tumor destruction. The gel particles carry large
      amounts of boron-10 and are theoretically able effect a meaningful tissue dosing
      through BNCT. A gross precipitation of gel particles occurs within 46 min of
      mixing when the avidin/colloid ratio is about 0.34 g avidin/g colloid. This is a
      minimum time if gel and avidin concentrations are in the low microgram/milliliter
      range, but at higher proportions of avidin the time delay to precipitation
      increases significantly; i.e., the colloid surface becomes blocked, inhibiting
      lattice formation. The avidin-coated gel particles eventually cross-link, forming
      a solid matrix and precipitating on a timescale measured on the order of an hour.
      At shorter exposure times rapid agglutination-like reactions were observed with
      biotinylated bovine albumin, suggesting that two-stage pretargeting of specific
      tissues should be possible with biotinylated antitumor antibodies. However, for
      BNCT to be practical, avidin's interaction with the gel needs to be strengthened,
      and all aryl-B(OH)(2) groups on the particle surfaces must be blocked, or else
      the particles will interact strongly and nonspecifically with each other and with
      the carbohydrate groups present on most cell surfaces. Glyceric acid delays the
      precipitation of the particle suspensions while most simple and complex
      carbohydrates accelerate it.

PMID- 14697697
TI  - Excluded volume effect of rat intestinal mucin on
      taurocholate/phosphatidylcholine mixed micelles.
AB  - The interaction of bile salt/phospholipid mixed micelles with an intestinal mucin
      has been investigated to provide the foundation for the transport of ingested fat
      and poorly water-soluble drugs through the intestinal mucous layer. Egg
      phosphatidylcholine (PC) was equilibrated with sodium taurocholate (TC) to
      generate several series of solutions, which had different intermicellar
      concentrations of TC. Within each series, each solution had the same IMC and
      thereby micelle sizes, but varied with respect to micelle concentration. These
      solutions were combined with isolated rat intestinal mucin, equilibrated, and
      then separated by centrifugation. The supernatant and mucin pellet were assayed
      for PC and TC, and the diffusion coefficient of PC was measured in the
      supernatant by PFG-SE NMR spectroscopy. For each series, four linear
      relationships were found; TC supernatant concentration plotted as a function of
      PC supernatant concentration; TC pellet concentration plotted as a function of PC
      pellet concentration; TC pellet concentration plotted as a function of TC
      supernatant concentration; and PC pellet concentration plotted as a function of
      PC supernatant concentration. Theoretical analysis of these results indicated
      that mucin excludes from 25 to 80% of the bile salt/phospholipid mixed micelles
      with greater exclusion observed with larger micelle size. There is preferential
      association of the taurocholate with intestinal mucin, when present in the mixed
      micelle region of the phase diagram. The association coupled with exclusion would
      allow mucin to modulate the concentration of bile salt at the epithelial surface.

PMID- 14697698
TI  - Investigation of structure factors in dense colloidal suspensions using frequency
      domain photon migration: polydisperse systems.
AB  - Frequency domain photon migration (FDPM) technique was employed to investigate
      the structure factors of dense, polydisperse colloidal suspensions. The angle
      integrated structure factors, [S(q)], extracted from FDPM measurements of
      scattering properties at volume fractions ranging from 0.05 to 0.4, were compared
      with the values predicted from the polydisperse hard sphere Percus-Yevick (HSPY)
      model, as well as decoupling approximation (DA) and local monodisperse
      approximation (LMA) models that incorporated independently measured particle size
      information. Results show that the polydisperse HSPY model is the most suitable
      for accounting for particle interactions which predominantly arise from volume
      exclusion effects. Furthermore, the influence of size polydispersity upon [S(q)]
      is most significant at high volume fractions. The static structure factors at
      small wave vector q, S(0), were also assessed from dual wavelength FDPM
      measurements by using the small wave number approximation as well as the local
      monodisperse approximation. The measured S(0) agrees well with the values
      predicted by the polydisperse HSPY model.

PMID- 14697699
TI  - Modification of low- and high-defect kaolinite surfaces: implications for
      kaolinite mineral processing.
AB  - A comparison is made of the mechanochemical activation of three low- and one high
      defect kaolinite using a combination of X-ray diffraction, thermal analysis, and
      DRIFT spectroscopy. The effect of mechanochemical alteration of the kaolinites is
      greater for the low-defect kaolinites. The effectiveness of the mechanochemical
      treatment is represented by the slope of the d(001) peakwidth-grinding time line.
      High-defect kaolinite is not significantly altered by the grinding treatment. The
      effect of mechanochemical treatment on peakwidth was independent of the presence
      of quartz; the quartz acts as an additional grinding medium. The effectiveness of
      the mechanochemical treatment depends on the crystallinity of the kaolinite. Two
      processes are identified in the mechanochemical activation of the kaolinite:
      first the delamination of kaolinite appears to take place in the first hour of
      grinding and second a recombination process results in the reaggregation of the
      ground crystals. During this process proton hopping occurs and reaction to form
      water takes place. This water is then adsorbed and coordinated to surface-active
      sites created during mechanochemical treatment.

PMID- 14697700
TI  - Mathematical modeling of polymer-induced flocculation by charge neutralization.
AB  - A detailed mathematical model for flocculation of colloidal suspensions in
      presence of salts and polymers is described and validated. In former case, the
      classical DLVO theory, which accounts for relevant variables such as pH and salt
      concentration, is incorporated into a geometrically sectioned discrete population
      balance model. For processes involving polymers, flocculation via simple charge
      neutralization is modeled using a modified DLVO theory in which the effect of
      adsorbed polymer layers on van der Waals attraction is included. The fractal
      dimension of aggregates is obtained by dynamic scaling of experimental data for
      time evolution of mean aggregate size. The particle surface potential is assumed
      to be approximately equal to the zeta potential. The model predictions are in
      close agreement with experimental results for flocculation of colloidal hematite
      suspensions in the presence of KCl and polyacrylic acid at different
      concentrations. In particular, given values of model parameters, e.g., Hamaker
      constant, fractal dimension, surface potential, and thickness of adsorbed polymer
      layer, the model can realistically describe the kinetics of flocculation by a
      simple charge neutralization mechanism and track the evolution of floc size
      distribution. Representative examples of sensitivity of the flocculation model to
      perturbations in surface potential and fractal dimension and to modification in
      the DLVO theory for polymer-coated particles are included.

PMID- 14697701
TI  - Flocculation of diatomite by methylated milk casein in seawater.
AB  - A new biodegradable flocculant was prepared from a common and inexpensive
      protein. Milk casein was methylated in a 0.05 M HCl methyl alcohol solution at
      room temperature. The methylated milk casein (MeCS), having a methylation degree
      of 81%, was applied to the separation or flocculation of diatomite in seawater
      (pH 8.1+/-0.1) at room temperature (18-23 degrees C). The flocculating ability of
      MeCS was evaluated by a sedimentation balance method (cumulative measurement
      method). The diatomite suspension was effectively flocculated by the addition of
      a small amount of MeCS (0.25 wt% of the diatomite weight). The results of
      sedimentation analysis showed that the size-frequency curve had a very sharp and
      high peak; thus the diatomite floc formed by MeCS had a rather uniform size. The
      settling velocity of diatomite floc at the appropriate MeCS dosages (0.25-2 wt%
      of diatomite) was about 3 x 10(-3) ms(-1).

PMID- 14697702
TI  - Luminescence quenching of tris(2,2'-bipyridine)ruthenium(II) by 2,6
      dimethylphenol and 4-bromo-2,6-dimethylphenol in sol-gel-processed silicate thin
      films.
AB  - The luminescence properties of tris(1,2-bipyridine)ruthenium(II)
      (Ru(bpy)(3)(2+)), included in different organically modified silicate gel
      matrixes were investigated. Spin and dip-coated thin films were prepared from
      methyltrimethoxysilane (MTMOS) and methyltriethoxysilane (MTEOS). A blue shift in
      the emission spectrum of the MLCT excited state of Ru(bpy)(3)(2+) with respect to
      the aqueous solution was observed in all the films, practically independent of
      the reaction pH used to prepare the "sol," silane-derived precursor, and
      procedure used (dip-coating or spin-coating) to obtain the film. A bimodal
      distribution of probe sites in the films was obtained from modeling of the
      emission decays by a double exponential and from application of the exponential
      series method. The parameters of the decay components depended principally on the
      thermal treatment used in the processing of the films. The lifetimes decreased
      with the increase in the drying temperature of the films; at the same time, the
      emission spectra showed a red shift and the luminescence efficiency decreased. A
      luminescence quenching of the ruthenium complex in the films by 4-bromo-2,6
      dimethylphenol and 2,6-dimethylphenol in aerated aqueous solution at pH 12 in
      contact with the film was also observed. The quenching plots obtained from
      luminescence intensities or luminescence intensity decay measurements showed a
      downward curvature. These plots could be fitted satisfactorily by a sum of two
      Stern-Volmer terms with quenching constants K(SV1) and K(SV2) associated with two
      different binding sites of the ruthenium complex. This result is indicative of
      the matrix microheterogeneity in the films and is fully consistent with the
      biexponential nature of the luminescence intensity decay profiles. The Stern
      Volmer parameter values for both sites in the films suggest that only a low
      percentage of the probe is accessible to the quencher and its respective constant
      K(SV1) is lower than in water.

PMID- 14697703
TI  - A triple-layer model of the surface electrochemical properties of clay minerals.
AB  - We propose an electrical triple-layer model (TLM) to describe the electrochemical
      properties of clay minerals. This model includes a speciation model of the active
      crystallographic surface sites plus a classical description of the Stern and
      diffuse layers. In addition to the surface charges associated with the surface
      groups (aluminols, silanols, and Al--O--Si sites), the model takes into account
      the degree of isomorphic substitution rate inside the crystalline network. The
      model computes both the zeta potential and the low-frequency (few kHz) surface
      conductivity as these two properties are equally important to interpret
      electrokinetic properties of colloids and clay-rich porous materials. For surface
      conductivity, the model comprises two contributions; one is associated with the
      Stern layer (dynamic Stern layer) and the second is associated with the excess of
      counterions located in the diffuse Gouy-Chapman layer. The parameters of the TLM
      model are optimized using the Simplex algorithm. Comparison between the model and
      the experimental data shows good agreement for a reasonable choice of parameters
      close to the a priori values determined from quartz and gibbsite. Surface
      conductivity of smectite appears rather independent of salinity, while for
      kaolinite, surface conductivity increases with salinity. In both cases, the Stern
      layer contribution to surface conductivity dominates but the contribution
      associated with the diffuse layer cannot be neglected.

PMID- 14697704
TI  - Clay-catalyzed reactions of coagulant polymers during water chlorination.
AB  - The influence of suspended clay/solid particles on organic-coagulant reactions
      during water chlorination was investigated by analyses of total product formation
      potential (TPFP) and disinfection by-product (DBP) distribution as a function of
      exchanged clay cation, coagulant organic polymer, and reaction time.
      Montmorillonite clays appeared to act as a catalytic center where the reaction
      between adsorbed polymer and disinfectant (chlorine) was mediated closely by the
      exchanged clay cation. The transition-metal cations in clays catalyzed more
      effectively than other cations the reactions between a coagulant polymer and
      chlorine, forming a large number of volatile DBPs. The relative catalytic effects
      of clays/solids followed the order Ti-Mont > Fe-Mont > Cu-Mont > Mn-Mont > Ca
      Mont > Na-Mont > quartz > talc. The effects of coagulant polymers on TPFP follow
      the order nonionic polymer > anionic polymer > cationic polymer. The catalytic
      role of the clay cation was further confirmed by the observed inhibition in DBP
      formation when strong chelating agents (o-phenanthroline and ethylenediamine)
      were added to the clay suspension. Moreover, in the presence of clays, total DBPs
      increased appreciably when either the reaction time or the amount of the added
      clay or coagulant polymer increased. For volatile DBPs, the formation of
      halogenated methanes was usually time-dependent, with chloroform and
      dichloromethane showing the greatest dependence.

PMID- 14697706
TI  - Penetration into three-dimensional complex porous structures.
AB  - The short-term uptake of a fluid by porous media is important in a number of
      processes, such as in coating and printing operations. We present a new model to
      predict short-term absorption into real pore geometries taking into account fluid
      properties, surface forces, and the complex pore geometry. Two assumptions are
      made to reduce the complexity of the situation: (1) the flow resistance between
      pores can be estimated from pore geometry or air permeability measurements, and
      (2) the volume of fluid in the constrictions between pores is small. Pores can be
      connected in any manner and can be in any arrangement. The absorption rates
      predicted by the model are compared to experimental values obtained with coating
      layers of plastic, kaolin, and calcium carbonate pigments. These coatings are
      characterized in terms of void fraction, pore size, contact angle, and
      permeability. The comparison is good for water and inks when the air permeability
      of the porous layer is used to determine the average resistance to flow in the
      sample. These resistance values are close to the values obtained from pore
      geometries estimated from particle packing simulations.

PMID- 14697705
TI  - The critical gas saturation in a porous medium in the presence of gravity.
AB  - The critical gas saturation, S(gc), denotes the volume fraction of the gas phase
      at the onset of bulk gas flow during the depressurization of a supersaturated
      liquid in a porous medium. In the absence of gradients due to viscous or gravity
      forces, S(gc) is controlled by nucleation, capillary forces, and the rate of
      decline of the supersaturation. In this paper we address one important additional
      effect, that of buoyancy. We use 2-D pore-network simulations, based on invasion
      percolation in a gradient (IPG), and corresponding scaling relations to obtain
      the dependence of S(gc) on the gravity Bond number, B, under conditions of slow
      growth, namely when mass transfer is sufficiently fast. The critical gas
      saturation approaches two plateau values at low and high Bond numbers. In the in
      between region it scales as a power law of B, which for a 2-D lattice is S(gc)
      approximately B(-0.91).

PMID- 14697707
TI  - Influences of colloidal stability and electrokinetic property on electrodialysis
      performance in the presence of silica sol.
AB  - Negatively charged silica sol is known to lead to fouling of anion exchange
      membranes during electrodialysis (ED) as a result of its deposition on the
      membrane surface. It is known that the fouling potential is related to the
      physical and electrochemical properties of the silica particles as well as those
      of the anion exchange membranes. In this study, the properties of the silica sol
      were characterized in terms of its particle size, turbidity, and zeta potential
      in order to predict their effects on the electrodialysis performance. In the
      stability of colloidal particles, the critical coagulation concentrations of
      silica sol were determined as functions of ionic strength, cation species, and
      solution pH. In the electrodialysis of NaCl solution containing silica sol with
      various concentrations of CaCl(2), the colloidal behavior related to deposition
      and transport was examined during and after electrodialysis. The electrodialysis
      experiments clearly showed that the deposition and transport of silica sol during
      electrodialysis were related to the colloidal stability of dispersion.

PMID- 14697708
TI  - Effect of a static magnetic field on ion transport in a cellulose membrane.
AB  - A cellulose membrane was exposed to the static magnetic field (SMF) in the
      presence of KCl solution and ion transport through the membrane was measured
      before and after the SMF exposure. SMF at 0.24 T significantly enhanced the rate
      of ion transport, especially after the first exposure (p<0.05), while the
      increased ion transport rate did not return to the initial basal level after
      exchange of the aqueous medium. These results suggest that an irreversible,
      temporal conformation change took place on the cellulose membrane or on the water
      bound to the cellulose surface. The accelerating effect of SMF on the ion
      transport seems to have occurred as a result of stabilized hydration layer on the
      cellulose surface.

PMID- 14697709
TI  - Memory effects on the interfacial characteristics of dioctadecyldimethylammonium
      bromide monolayers at the air-water interface.
AB  - The structural and dynamic characteristics of dioctadecyldimethylammonium bromide
      (DODAB) monolayers on a pure water subphase were investigated by surface film
      balance, Brewster angle microscopy, and relaxation in area and surface pressure
      at constant surface pressure and area, respectively. The first compression
      expansion cycle of the monolayer is not reversible and the second pi-A
      compression isotherm deviates to larger molecular areas relative to the first
      one. At a microscopic level this hysteresis may be assigned to an irreversible
      hydration of the ammonium groups of DODAB. The morphology and reflectivity of
      DODAB monolayers during compression and expansion on the monolayer depend on the
      monolayer history. Bright domains randomly dispersed were observed during
      compression before collapse. Surprisingly, this random distribution of domains
      changes into a fractal-like structure during the monolayer expansion in a narrow
      range of surface pressures. This morphology does not form when the monolayer is
      previously compressed above the collapse surface pressure. 2D foam-like structure
      is often observed when the film is expanded at maximum area. Relaxation phenomena
      in DODAB monolayers are attributed to monolayer reorganization and nucleation of
      liquid-condensed domains from the liquid-expanded phase. These time-dependent
      processes are irreversible.

PMID- 14697710
TI  - On the calculation of disjoining pressure isotherms for nonaqueous films.
AB  - A review of the methods of London and Hamaker and of Lifshitz for calculating
      disjoining pressure isotherms of nonaqueous liquid films is presented. The
      disjoining pressure isotherms for films of n-octane and of three triglycerides
      (tributyrin, tricaprylin, and triolein) on glass were calculated using both
      methods. The disjoining pressure isotherms for films on silanized glass were
      calculated using only the London-Hamaker approach. The refractive indices and
      static dielectric constants, necessary for the calculations, were measured. The
      silanized glass was considered to be the original glass covered by a layer with
      the same characteristic frequency as the underlying glass and a smaller limiting
      value of the dielectric constant epsilon(0). The limiting dielectric constant
      epsilon(0) and the thickness of the surface layer were taken as adjustable
      parameters. The disjoining pressure isotherms indicate that all films are stable
      on glass. In contrast, the stability of the films formed on silanized glass was
      found to depend mainly on the value of epsilon(0) and, less strongly, on the
      thickness of the surface layer. The stability of the films decreased with the
      decrease of epsilon(0) and, for each value of epsilon(0), was maximal for the
      thinnest surface layer.

PMID- 14697711
TI  - A comparative study on textural characterization: cation-exchange and sorption
      properties of crystalline alpha-zirconium(IV), tin(IV), and titanium(IV)
      phosphates.
AB  - Tetravalent metal phosphates (M=Zr, Ti, and Sn) were prepared and characterized
      by XRD, surface properties, and TG-DTA. The cation exchange and sorption behavior
      of these metal phosphates toward transition metal ions such as Cu(2+), Co(2+),
      and Ni(2+) have been studied comparatively as a function of temperature and
      concentration. The adsorption process was found to increases with increase in
      temperature and concentration. The selectivity order for alpha-titanium and alpha
      tin phosphates is Cu(2+)>Co(2+)>Ni(2+), whereas for alpha-zirconium phosphate it
      is Cu(2+)>Ni(2+)>Co(2+). The ion exchange capacity of alpha-titanium phosphate is
      greater than those of other phosphates, which is explained on the basis of the
      surface behavior, disorderness of the system, degree of hydrolysis of incoming
      guest adsorbate metal ions, and structural steric hindrance of the exchangers
      during adsorption and sorption. The distribution coefficient, Gibbs free energy,
      enthalpy, and entropy values indicate that the ion-exchange processes are
      spontaneous.

PMID- 14697712
TI  - Development of urethane acrylate composite ion-exchange membranes and their
      electrochemical characterization.
AB  - With the objective of introducing antifouling characteristics into interpolymer
      types of cation and anion exchange membranes, the surface of these membranes was
      coated with a 12-microm-thick urethane acrylate layer and was cured by UV
      radiation of wavelengths 308 and 172 nm under a complete inert atmosphere.
      Different urethane acrylate composite ion exchange membranes developed were
      characterized in NaCl solution by measuring their ion-exchange capacity, volume
      fraction of water, contact angle with water, membrane conductance, and membrane
      potential. It was found that the electrochemical transport properties of urethane
      acrylate composite cation-exchange membranes were increased due to resonance
      stabilization of the urethane group, which acts as a weak acid and dissociates as
      a negatively charged urethane ion and a positively charged proton. This
      contributes toward the net charge density of the membrane matrix responsible for
      enhanced selectivity and conductivity, while for urethane acrylate composite
      anion-exchange membranes reduction in net charge density was responsible for
      reduction in electrochemical transport properties. Counterion transport number,
      permselectivity, and counterion diffusion coefficient values for these membranes
      were also estimated. Experiments were also carried out in higher homologs of
      sodium carboxylate solutions in order to observe the fouling tendencies of these
      membranes. It was concluded that it is possible to obtain antifouling
      characteristics of ion-exchange membranes by coating and curing thin hydrophilic
      layers of urethane acrylate on their surfaces without sacrificing their
      electrochemical transport properties.

PMID- 14697713
TI  - Surface energy of solid catalysts measured by inverse gas chromatography.
AB  - The time separation of experimental surface energy on Pt-Rh bimetallic catalysts,
      together with the time-independent rate constants for adsorption and desorption
      of O(2), CO, and CO(2) on them, is described, applying the reversed-flow version
      of inverse gas chromatography. The standard free energy of adsorption
      DeltaG(z.plims;) and its probability density function over time, together with
      the geometrical mean of the London parts of the total surface free energy
      (gamma(L)(1)gamma(L)(2))(1/2) of the adsorbed probe and the solid surface,
      accompanied by the relevant probability density functions over time are also
      calculated. The time-resolved phenomena lead to quite varying values of
      DeltaG(z.plims;), (gamma(L)(1)gamma(L)(2))(1/2), and the distribution functions
      as time passes, their maximum values being given by the catalyst containing a
      Pt:Rh = 3:1 weight ratio of the active phase for all adsorbed gases. The
      conclusion is reached that the surface energy measured as described can be used
      as a good measure for catalyst characterization.

PMID- 14697714
TI  - Microscale thermoviscosity and evaporation at the three-phase contact zone.
AB  - A microscale model of wetting at the three-phase contact zone that incorporates
      the thermoviscosity effect under nonisothermal and evaporation conditions is
      presented. The thermoviscosity effect is shown to change the content of both
      governing equations and boundary conditions. The differential equation of the
      liquid-vapor interface profile is expressed in terms of previously defined
      dimensionless groups and the new thermoviscosity change factor D(s). The
      temperature-dependent viscosity eta(T), and capillary number C(*) are defined as
      a product of eta and C and of 1-D(s)Theta(I), respectively. Model outputs show
      that increase of D(s) decreases the wave length and amplitude of the solution
      profile as well as the film thickness and slope. In the tested cases of water,
      nitrogen, and helium, increase of D(s) extends the physically feasible range of
      contact angle and wall temperature versus fluid velocity. Under rewetting
      conditions, the effect of increased D(s) is to shift the allowable range of wall
      temperatures toward smaller values, concurrent with increasing the feasible
      values of corresponding quench velocities. The capacity of the dimensionless
      groups, C, Ctheta(2)/F, N, and A, to change the liquid-vapor interface profile is
      diminished by D(s), the capillary number C and the Hamaker constant being most
      and least sensitive in this respect.

PMID- 14697715
TI  - Interpretation of surface dilational elasticity data based on an intrinsic two
      dimensional interfacial compressibility model.
AB  - The present analysis shows that the introduction of intrinsic two-dimensional
      compressibility of a surfactant adsorption layer allows a much better
      interpretation of experimental data on the limiting (high-frequency) elasticity
      and characteristic frequency of diffusional relaxation than models using
      Frumkin's or other adsorption isotherms. The proposed model describes
      experimental data on surface dilational elasticity, as well as on surface
      pressure, sufficiently well at low and high surfactant concentrations, assuming
      the Lucassen and van den Tempel model of surface dilational elasticity is
      realized.

PMID- 14697716
TI  - Phase diagrams and microstructure of aggregates in mixed ionic surfactant/foam
      booster systems.
AB  - The phase behavior and microstructure of surfactant systems containing a new
      alkanolamide-type foam booster, dodecanoyl N-methyl ethanolamide (NMEA-12), were
      investigated by means of phase study and small angle X-ray scattering. Different
      from other similar alkanolamides, NMEA-12 possesses a low melting point and forms
      a lyotropic liquid-crystalline phase (L(alpha) phase) at room temperature. This
      is attributed to the attached methyl group, which increases the fluidity of the
      molecule. In the SDS/NMEA-12/water system, hexagonal and lamellar (L(alpha))
      liquid-crystalline phases are obtained at significantly low surfactant
      concentrations. The stability of these phases decreases when SDS is replaced with
      a nonionic surfactant (C12EO8). However, for both ionic and nonionic surfactants,
      the effective area per surfactant molecule at the interface shrinks upon addition
      of NMEA-12, indicating that the surfactant layer is getting more compact. The
      possible implications of these results on the potential applications of NMEA-12
      as foam stabilizer are discussed.

PMID- 14697717
TI  - Interaction between pentaethylene glycol n-octyl ether and low-molecular-weight
      poly(acrylic acid).
AB  - The interaction between pentaethylene glycol n-octyl ether (C8E5) and low
      molecular-weight poly(acrylic acid) (PAA, M(w)=2000) in aqueous solution has been
      investigated by various experimental techniques at constant polymer concentration
      (0.1% w/w) with varying surfactant molality. Spectrofluorimetry, using pyrene as
      molecular probe, shows (i) the formation of surfactant-polymer aggregates at a
      surfactant molality (T(1)) lower than the critical micelle concentration (cmc) of
      C8E5 in water and (ii) the formation of free micelles at a surfactant molality
      (T(2)) slightly higher than the cmc. Fluorescence quenching measurements indicate
      that the presence of PAA induces a lowering of the C8E5 aggregation number.
      Calorimetry confirms spectrofluorimetric evidence; in addition, it shows the
      presence of weak interactions below T(1) between monomeric surfactant molecules
      and the polymer chains. Tensiometry shows that, above T(1), only a low fraction
      of surfactant molecules interact with the polymer and that free micelle formation
      occurs before polymer saturation. The peculiarities of the interaction between
      surfactants and low-molecular-weight polymers have been discussed.

PMID- 14697718
TI  - Resistance in series model for micellar enhanced ultrafiltration of eosin dye.
AB  - A study has been performed to quantify the extent of flux decline during micellar
      enhanced ultrafiltration (MEUF) of an acid dye (eosin red) using hexadecyl
      (cetyl) pyridinium chloride as the cationic surfactant. Effects of the operating
      conditions, e.g., transmembrane pressure drop and feed-surfactant-to-dye ratio,
      on the permeate flux profile and observed retention have been investigated in an
      unstirred batch ultrafiltration (UF) cell. A simple resistance-in-series model
      has been used to quantify the flux decline. From the flux decline history, it has
      been found that the membrane permeability decreases rapidly due to reversible
      pore blocking and further flux decline is caused by the growth of a gel-type
      layer over the membrane surface. The different resistances and growth kinetics of
      the gel layer have been investigated as functions of the operating conditions.

PMID- 14697719
TI  - Paraseptal accessory connections in the proximity of the atrioventricular node
      and the His bundle. Additional observations in relation to the ablation technique
      in a high risk area.
AB  - INTRODUCTION: Paraseptal pathways, namely, accessory connections (AC) in the
      vicinity of the atrioventricular node (AVN) and the bundle of His, are associated
      with a high risk of complete atrioventricular block (AVB) during transcatheter
      radiofrequency ablation (RFA) in the Electrophysiology Laboratory. In previously
      reported series of ablation of paraseptal ACs, the coexistence of multiple ACs in
      this high-risk region has rarely been mentioned. METHODS AND RESULTS: We studied
      15 patients undergoing RFA of paraseptal ACs 2 of whom had dual pathways with an
      additional midseptal pathway revealed after the elimination of the anteroseptal
      target AC. The fundamental goal of the pre-ablation electrophysiological mapping
      was the clear-cut determination of anatomical site with His bundle recording
      activity. This required unique pharmacological and programmed electrical
      stimulation manipulations in 8 patients in whom His bundle recording activity was
      only temporarily possible. After identifying the corresponding His bundle site,
      special attention was given to the ablation catheter being situated at least 3 mm
      away, thus recording minimal or no His bundle activity. Additional precautions
      were taken so that the delivered therapy was of minimal duration and powered by
      temperature regulation with immediate interruption in case of AVB or nodal rhythm
      appearance. With this therapeutic approach, 16 of the 17 paraseptal ACs were
      ablated successfully with the inadvertent induction of AVB in only 1 patient. In
      the patient with persistent ventricular preexcitation after the ablation session,
      modification of both the AC and the AVN was noted so that the previously easily
      induced reciprocating atrioventricular tachycardia was no longer so, using
      programmed stimulation. CONCLUSION: Transcatheter radiofrequency ablation is a
      feasible and effective radical therapy for patients with paraseptal ACs, provided
      the His bundle site has first been clearly defined and the coexistence of other
      nearby tracts has been excluded.

PMID- 14697720
TI  - Modulation of the slow pathway in the presence of a persistent left superior
      caval vein using the novel magnetic navigation system Niobe.
AB  - AIMS: This is the first report of a young female with typical AVNRT in the
      presence of a persistent left superior caval vein that underwent catheter
      ablation using the novel magnetic navigation system (MNS) Niobe (Stereotaxis
      Inc.). METHODS: The MNS consists of two outer permanent magnets (about 0.1 T)
      that align a third small magnet integrated in the tip of a mapping and ablation
      catheter along its magnetic field lines. By changing the orientation of the outer
      magnets, the orientation of the magnetic field lines also change, thereby
      allowing navigation of the ablation catheter. In combination with an automated
      advancer system, this novel technique allows for the first time complete remote
      catheter ablation. RESULTS: Successful slow pathway modulation was performed
      using a total of seven radiofrequency current applications via the magnetic
      ablation catheter. No complication occurred. CONCLUSIONS: The novel magnetic
      navigation system proved to be a safe and feasible tool for remote catheter
      ablation of common type AVNRT in the presence of a persistent left superior caval
      vein.

PMID- 14697721
TI  - Incidence and management of early recurrent atrial fibrillation (ERAF) after
      transthoracic electrical cardioversion.
AB  - AIMS: The purpose was to determine the incidence of early recurrent atrial
      fibrillation (ERAF) after transthoracic cardioversion (CV) of persistent atrial
      fibrillation (AF) and to evaluate the efficacy of a predefined strategy for its
      management. METHODS AND RESULTS: Consecutive patients (n=135) underwent elective
      CV of AF. CV was performed according to a predefined step-up protocol with rising
      energy delivery (200 J to 360 J). ERAF was defined as a relapse of AF within 1
      min after at least two sinus beats. For proper identification of success of CV,
      additional endocardial recordings were obtained by an electrode catheter
      positioned in the high right atrium. In case of ERAF, further CVs were attempted,
      first with higher energy delivery only, second after intravenous flecainide. If
      transthoracic CV was ineffective, an internal CV was scheduled. All patients
      could be converted into sinus rhythm. Sixteen patients (12%) had ERAF. ERAF could
      be suppressed by further shock delivery in 31% of them. In the remaining 69%, a
      combination of i.v. flecainide and repeated CV was effective in controlling ERAF.
      Clinical and echocardiographic parameters were comparable in patients with or
      without ERAF. CONCLUSION: (1) In the patient population studied, transthoracic CV
      of AF was technically highly efficacious, so that an internal CV was not
      necessary in any of the cases. (2) Clinical success of transthoracic
      cardioversion was limited by ERAF in 12% of the patients. (3) Using the described
      protocol, ERAF could be suppressed in all patients.

PMID- 14697722
TI  - Evaluation of body weight as a predictive factor for transvenous ventricular
      defibrillation characteristics.
AB  - AIMS: To investigate the correlation between body weight and defibrillation
      threshold (DFT) for transvenous lead systems using a porcine model. METHODS AND
      RESULTS: Twenty-eight pigs were anaesthetised and DFTs assessed in single and
      dual coil configurations using a four-reversal binary search method. DFT was
      correlated with body weight in the RV --> Can and RV --> SVC + Can
      configurations. A Pearson correlation coefficient and a two-sided p-value were
      calculated. A positive correlation exists between body weight and DFT in RV -->
      Can (r=0.66, p<0.000) and RV --> SVC + Can (r=0.44, p=0.018). CONCLUSION: There
      is a significant correlation between body weight and DFT in swine. This tends to
      be greater in the two-electrode than in the three-electrode configuration. With
      these and previous human observations, one may predict a higher DFT in heavy
      individuals and make appropriate procedural adjustments.

PMID- 14697723
TI  - Incidence of venous obstruction following insertion of an implantable
      cardioverter defibrillator. A study of systematic contrast venography on patients
      presenting for their first elective ICD generator replacement.
AB  - AIMS: The number of implantable cardioverter defibrillator (ICD) implantations,
      as well as follow-up procedures such as generator exchanges, lead revisions and
      lead system upgrades, is ever-increasing. Lead revisions and implantation of
      additional leads require venous access at the site of the previous ICD
      implantation. The aim of our study was therefore to evaluate the incidence of
      venous obstruction after chronic transvenous ICD system implantation. METHODS AND
      RESULTS: One hundred and five consecutive patients admitted for their first
      elective ICD generator replacement were included. All patients underwent
      bilateral contrast venography and the images were analyzed by two attending
      radiologists. Venous obstruction was classified as moderate stenosis (50-75%
      diameter reduction), severe stenosis (>75%) or total occlusion. Venous
      obstruction of various degrees was found in 25% of the patients. Complete
      occlusion was found in 9%, severe stenosis in 6% and moderate stenosis in 10% of
      the patients. The incidence of venous obstruction was increased in patients with
      a pacemaker prior to the initial ICD system implantation (67%). No difference was
      found in patients with a single defibrillator lead compared with patients who had
      an additional superior vena cava (SVC) shocking coil. However, the presence of a
      second shocking coil in the SVC incorporated in a single ICD lead was associated
      with an increased incidence of venous obstruction. No difference was found
      between silicone and polyurethane insulated leads. CONCLUSION: This study shows
      that venous obstruction occurs relatively frequently after ICD implantation.
      Therefore, contrast venography should always be obtained if malfunction of a
      preexistent lead is suspected or a system upgrade is considered.

PMID- 14697724
TI  - Performance of a dual-chamber implantable defibrillator algorithm for
      discrimination of ventricular from supraventricular tachycardia.
AB  - BACKGROUND: Inappropriate therapies remain a major problem in patients with
      implantable cardioverter defibrillators (ICDs). Decreasing the proportion of
      inappropriate therapies is a major objective. With the addition of atrial
      detection and advanced algorithms, dual-chamber ICDs are designed to offer better
      discrimination of ventricular (VT) and supraventricular (SVT) arrhythmias. The
      present multicentre, open study aimed to evaluate the performance of a dual
      chamber detection algorithm, the Atrial View algorithm, incorporated in a dual
      chamber ICD, the Ventak AV (Guidant Inc., St. Paul, Minnesota, USA). METHODS AND
      RESULTS: Fifty-one patients (45 males, 62+/-11 years, ejection fraction 42+/-15%)
      with standard indications received a Ventak AV ICD which analyzes, within the VT
      zone RR stability, tachycardia onset, atrial rate and AV relationship.
      Predischarge enhanced-detection algorithms were prospectively programmed:
      stability 24 ms, onset 9%, atrial fibrillation threshold 200 beats/min, and
      Vrate>Arate. An additional sustained rate duration criterion was programmed at
      least at 30 s. ICDs were interrogated every 3 months or when patients received
      shocks. A blinded review of electrograms for arrhythmia diagnosis and
      appropriateness of therapy was performed by 2 experts. Over the follow-up period
      (12+/-3.6 months), a total of 400 tachycardia episodes was recorded within the VT
      zone. After the review of stored electrograms, 237 (59%) true positive, 143 (36%)
      true negative, 17 (4%) false positive and 3 (1%) false negative episodes were
      diagnosed. Considering the 3 VTs incorrectly detected by the detection
      algorithms, therapy was delivered in 2 cases after sustained rate duration and 1
      VT reverted spontaneously. Inappropriate therapy occurred in 17 cases. All but 1
      were related to SVT with 1:1 atrioventricular relationship. Finally, on a per
      episode basis, the detection algorithm sensitivity was 99% and specificity was
      89%. CONCLUSIONS: Programming of detection criteria based on stability, onset,
      atrial fibrillation rate threshold and Vrate>Arate allows a 99% sensitivity and
      an 89% specificity in Guidant ICDs. Discrimination of SVT with 1:1
      atrioventricular relationship, however, remains a challenge for which new
      algorithms have to be designed.

PMID- 14697725
TI  - Major dissection of the coronary sinus and its tributaries during lead
      implantation for biventricular stimulation: angiographic follow-up.
AB  - Dissection of the coronary sinus during lead implantation for biventricular
      pacemaker implantation in patients with advanced heart failure is a serious
      complication that has occasionally been reported. We report on the clinical
      outcome and angiographic follow-up in a series of 7 patients with acute major
      dissection from 103 consecutive attempts (incidence 6.8%). Serial
      echocardiography was performed in all patients and all underwent follow-up
      angiography 2-3 months after the procedure. In 1 patient, pericardial
      extravasation was seen during retrograde venography. Clinical follow-up was
      uneventful except for one other patient who complained of prolonged chest
      discomfort for several hours after the procedure. In none of the patients were
      there signs of pericardial effusion or tamponade demonstrated on
      echocardiography. Venograms during the procedure and after follow-up were
      analysed using a quantitative coronary angiography system (CAAS II). Parameters
      included minimal luminal diameter, diameter stenosis, minimal cross-sectional
      area and an estimation of the reference diameter. There were no significant
      differences in all analysed parameters, although in 1 patient a small partial
      dissection was present. Thus, although dissection of the coronary sinus following
      lead implantation for biventricular stimulation is not an uncommon complication,
      it is usually well tolerated. Long-term angiographic follow-up demonstrated no
      significant vessel damage or vessel remodeling.

PMID- 14697726
TI  - Transient modification of baroreceptor response during tilt-induced vasovagal
      syncope.
AB  - AIMS: Normally, arterial baroreceptors attempt to minimize systemic hypotension
      by initiating reflex vasoconstriction and tachycardia. However, in the setting of
      vasovagal syncope (VVS), these usual compensatory mechanisms either fail to be
      triggered or the response is inadequate. We hypothesized that in VVS prone
      individuals, arterial baroreceptor response (BRR) is normal under most
      conditions, but that a transient functional BRR disturbance occurs during an
      evolving vasovagal faint and may in part account for failure of the usual
      compensatory response. METHODS AND RESULTS: This study assessed BRR in the
      baseline state and again in association with either VVS induced head-up tilt
      (HUT) or after a prolonged period of upright posture without VVS. To minimize
      impact on HUT outcome, BRR was estimated non-pharmacologically by measuring blood
      pressure and heart rate changes, induced when subjects were returned to the
      supine position after undergoing diagnostic 70 degrees HUT evaluation. Beat to
      beat heart rate and arterial blood pressure changes were recorded in 13 patients
      with syncope and another 16 individuals with negative HUT (control group).
      Baseline BRR was initially evaluated at the end of a 3 min symptom free HUT
      (HUT#1), and the measurement was repeated after a 45 min duration HUT in the
      control group or in conjunction with syncope in VVS prone individuals (HUT#2).
      Baseline BRR did not differ significantly in controls and VVS prone individuals
      (controls: 3.37+/-1.56, VVS prone: 6.0+/-2.02 ms/mmHg, p=0.27). Further, at the
      end of 45 min HUT#2, BRR was unaltered from baseline in control subjects (4.92+/
      1.36 ms/mmHg, p=0.48), but was markedly reduced from baseline value in
      individuals who experienced a faint, -3.30+/-0.81 ms/mmHg (p<0.0003 vs baseline).
      CONCLUSION: Compared with individuals who do not manifest VVS during HUT, VVS
      prone individuals appear to demonstrate functional diminution of baroreceptor
      responsiveness. This altered response may undermine the normal expected
      compensatory response to evolving systemic hypotension. The basis for this
      transient disturbance in baroreceptor responsiveness is currently unknown.

PMID- 14697727
TI  - Clinical spectrum of neurally mediated reflex syncopes.
AB  - AIMS: The clinical features of the various types of neurally mediated reflex
      syncope have not been systematically investigated and compared. We sought to
      assess and compare the clinical spectrum of neurally mediated reflex syncopes.
      METHODS AND RESULTS: Four hundred sixty-one patients with syncope were
      prospectively evaluated and 280 had neurally mediated reflex syncope. Each
      patient was interviewed using a standard questionnaire. A cause of syncope was
      assigned using standardized diagnostic criteria. Typical vasovagal syncope was
      diagnosed in 39 patients, situational syncope in 34, carotid sinus syncope in 34,
      tilt-induced syncope in 142 and complex neurally mediated syncope (positive
      response to both carotid sinus massage and tilt test) in 31. The clinical
      features of situational, carotid sinus, tilt-induced and complex neurally
      mediated syncope were very similar. By contrast, typical vasovagal syncope
      differed from other neurally mediated syncopes not only in terms of its
      precipitating factors (fear, strong emotion, etc.), which constituted predefined
      diagnostic criteria, but also in the variety of its clinical features (lower age
      and prevalence of organic heart disease, higher prevalence of prodromal symptoms,
      and of autonomic prodromes, longer duration of prodromes, higher prevalence of
      symptoms during the recovery phase and lower prevalence of trauma). CONCLUSION:
      The clinical spectrum of neurally mediated reflex syncopes demonstrates much
      overlap between them. However, when the afferent neural signals are localized in
      cortical sites, as in typical vasovagal syncope, symptoms are more frequent and
      of longer duration.

PMID- 14697728
TI  - Transcranial Doppler monitoring during head upright tilt table testing in
      patients with suspected neurocardiogenic syncope.
AB  - The aim of the present study was to evaluate the mechanism of cerebrovascular
      autoregulation in patients with neurocardiogenic syncope using bilateral
      transcranial Doppler (TCD) monitoring during head upright tilt table testing
      (HUT). Two hundred and six patients were prospectively studied. One hundred and
      fifty-nine subjects (77%) had a prior history of syncope and 47 (23%) had
      presyncope. Ninety-nine patients (48%) had syncope or presyncope during HUT with
      a 76% fall in diastolic middle cerebral artery blood flow velocity (D-MCA-BFV).
      Systolic MCA-BFV (S-MCA-BFV) fell by 33%. Deepening of the dicrotic notch in the
      Doppler waveform always preceded the fall in D-MCA-BFV. Patients without syncope
      or presyncope (n=96) had smaller changes in cerebral blood flow velocities during
      HUT and only twenty-two subjects had transient deepening of the dicrotic notch.
      Eleven subjects had presyncope during HUT due to an exaggerated response to
      nitrates with progressive arterial hypotension without bradycardia and changes
      during TCD monitoring that were intermediate between positive and negative HUT.
      In conclusion, patients with neurocardiogenic syncope have changes in cerebral
      blood flow during the event. TCD monitoring during HUT helps to assess these
      alterations.

PMID- 14697729
TI  - Value of the implantable loop recorder for the management of patients with
      unexplained syncope.
AB  - AIM: Recurrent syncope often remains unexplained despite extensive
      multidisciplinary screening. The implantable loop recorder (ILR) may be a tool to
      define the cardiac arrhythmias underlying syncope. METHODS AND RESULTS: The study
      population consisted of 43 consecutive patients with unexplained syncope who
      underwent extensive cardiological screening and were followed with an ILR. During
      follow-up, 5 patients had only presyncope, 4 had palpitations, and 15 had a true
      recurrence of syncope. In all patients with palpitations, 3 with presyncope, and
      7 with a recurrence of syncope, the ILR excluded arrhythmias. In the patients
      with a true recurrence, 1 had symptomatic paroxysmal atrial fibrillation (PAF)
      treated with drugs, 1 had polymorphic ventricular tachycardia (VT) and received
      an implantable cardioverter defibrillator (ICD), and 7 had asystole and received
      a pacemaker. Two patients with presyncope received a pacemaker for Mobitz II
      block and PAF with brady-tachycardia syndrome. One asymptomatic patient received
      a pacemaker for significant nocturnal asystole recorded by ILR. Abnormalities in
      the cardiac screening were observed both in patients with and without syncope,
      but none of these had a predictive value. CONCLUSION: The ILR is a valuable and
      effective tool to establish an arrhythmic cause for unexplained syncope. The
      results of head-up tilt testing (HUTT) and electrophysiological study (EPS) are
      neither sufficiently sensitive nor specific enough in this patient group.

PMID- 14697730
TI  - Images in pacing. Fusion of permanent pacing leads.

PMID- 14697731
TI  - Cryoprotectin protects thylakoids during a freeze-thaw cycle by a mechanism
      involving stable membrane binding.
AB  - Chloroplast thylakoid membranes of higher plants are damaged by freezing both in
      vivo and in vitro. The resulting inactivation of photosynthetic electron
      transport has been related to transient membrane rupture, leading to the loss of
      soluble electron transport proteins and osmotically active solutes from the
      thylakoid lumen. We have recently purified and sequenced a protein from cold
      acclimated cabbage, that protects thylakoids from this freeze-thaw damage. The
      protein belongs to the WAX9 family of nonspecific lipid transfer proteins, but
      has no detectable lipid transfer activity. Conversely, other transport-active
      lipid transfer proteins show no cryoprotective activity. We show here that
      cryoprotectin binds to thylakoid membranes. Both cryoprotective activity and
      membrane binding were inhibited in the presence of specific sugars, most
      effectively by Glc-6-S. The binding of cryoprotectin to thylakoids reduced the
      fluidity of the membrane lipids close to the membrane/solution interface, but not
      in the hydrophobic core region. Using immobilized liposomes we could show that
      cryoprotectin was able to bind to pure lipid membranes.

PMID- 14697732
TI  - Effect of different cryoprotectants and vitrificant solutions on the hatching
      rate of turbot embryos (Scophthalmus maximus).
AB  - Vitrification could provide a promising tool for the cryopreservation of fish
      embryos. However, in order to achieve a vitrifiable medium, a high concentration
      of permeable cryoprotectants must be employed, and the incorporation of high
      molecular weight compounds should also be considered. The toxicity of these
      permeable and non-permeable agents has to be assessed, particularly when high
      concentrations are required. In the present study, permeable and non-permeable
      cryoprotectant toxicity was determined in turbot embryos at two development
      stages (F stage-tail bud and G stage-tail bud free). Embryos treated with pronase
      (2mg/ml, 10 min at 22 degrees C) were incubated in dimethyl sulfoxide (Me2SO),
      methanol (Meth.) or ethylene glycol (EG) in concentrations ranging from 0.5 to 6M
      for periods of 10 or 30 min, and in 5, 10, and 15% polyvinylpyrrolidone (PVP),
      10, 15, and 20% sucrose or 0.1, 1, and 2% X-1000 for 2 min. The embryos were then
      washed well and incubated in seawater until hatching. The toxicity of permeable
      cryoprotectants increased with concentration and exposure time. There were no
      significant differences between permeable cryoprotectants. However, embryos
      tolerated higher concentrations of Me2SO than other cryoprotectants. Exposure to
      permeable cryoprotectants did not affect the hatching rate except at G stage with
      X-1000 treatment and 20% sucrose. Taking into account the cryoprotectant toxicity
      and the vitrification ability of cryoprotectant mixtures, three vitrification
      solutions (V1, V2, and V3), and one protocol for stepwise incorporation were
      designed. The tested solutions contained 5M Me2SO+2M Meth+1M EG plus 5% PVP, 10%
      sucrose or 2% X-1000. The hatching rate of embryos that had been exposed to the
      the vitrification solutions was analyzed and no significant differences were
      noticed compared with the controls. Our results demonstrate that turbot embryos
      can be subject to this cryoprotectant protocol without deleterious effect on the
      hatching rate.

PMID- 14697733
TI  - A pig model of hepatic cryotherapy. In vivo temperature distribution during
      freezing and histopathological changes.
AB  - We aimed to assess the temperature distribution in the cryolesion during hepatic
      cryotherapy and the association with postoperative histological changes to
      optimise the technique and allow better preoperative planning. Hepatic
      cryolesions were produced in 22 pigs following laparotomy using a CMS-cryosystem
      and 8mm-AccuProbe-Cryoprobes. The temperature was measured in 1 min intervals at
      different distances from the probe during freezing. The animals were treated in 5
      groups: (i) single freezing of 20 min; (ii) double freezing of 20 min each; (iii)
      single freezing of 40 min; (iv) single freezing of 20 min (n=4), histology at 1
      week p.o., and (v) single freezing of 20 min and Pringle manoeuvre; [(i)-(iii)
      and (v): histology at 24 h p.o.]. The mean diameter of the -38 degrees C
      isotherm, i.e., the zone of effective treatment for colorectal metastases was 37
      mm for group (i) with a mean iceball diameter of 59 mm and about 46 mm for groups
      (ii, iii, and v) with mean iceball diameters of 78, 75, and 75 mm, respectively.
      At 7 days postoperatively secondary necrosis was seen in the largest central part
      of the lesion, wherever temperatures of -15 degrees C or lower were achieved
      during cryosurgery. Under the hypothesis that -38 degrees C is the effective
      temperature for the destruction of colorectal liver metastases, a lesion of 37-mm
      diameter may be effectively treated with a single 8mm-AccuProbe-Cryoprobe and a
      20 min single freeze cycle and a lesion of 46 mm may be effectively treated when
      a double freeze-thaw cycle of 20 min each, a single freeze cycle of 40 min, or a
      20 min single freeze cycle with additional Pringle manoeuvre is used, when it is
      perfectly placed in the lesion.

PMID- 14697734
TI  - Evaluation of DNA damage in Dicentrarchus labrax sperm following
      cryopreservation.
AB  - In this paper, DNA laddering analysis and single-cell gel electrophoresis (SCGE)
      or Comet assay, were used to detect DNA damage in response to a cryopreservation
      process in sea bass spermatozoa. The results obtained demonstrate that the
      cryopreservation protocol used to cryopreserve the sea bass sperm cause
      significantly damage at DNA level. In fact, the degree of DNA damage in frozen
      thawed sperm (%DNAT=38.2+/-11.2, MT=498.9+/-166.4, n=3) was different (P<0.01)
      from that measured in fresh sperm (%DNAT=32.7+/-11.1, MT=375.2+/-190.7, n=3).
      Data here reported also demonstrated the fundamental role played by
      cryoprotectants (BSA and Me2SO) in reducing fish sperm DNA fragmentation.
      Finally, from our results, the ability of SCGE to reveal DNA fragmentation in
      fish sperm is also confirmed.

PMID- 14697735
TI  - The role of glutathione in yeast dehydration tolerance.
AB  - Among the factors that affect cell resistance against dehydration, oxidation is
      considered to be of great importance. In this work, we verified that both control
      and glutathione deficient mutant strains were much more oxidized after
      dehydration. Moreover, cells lacking glutathione showed a twofold higher increase
      in oxidation and lipid peroxidation than the control strain. While glucose 6
      phosphate dehydrogenase and glutathione reductase activities did not change in
      response to dehydration in the control strain, the mutant strain gsh1
      (glutathione deficient) showed a reduction of 50% in both activities, which could
      explain the high levels of oxidation shown by gsh1 cells. In conformity with
      these results, the mutant lacking GSH1 showed a high sensitivity to dehydration.
      Furthermore, the addition of glutathione to gsh1 cells restored survival rates to
      the levels of the control strain. We conclude that glutathione plays a
      significant role in the maintenance of intracellular redox balance during
      dehydration.

PMID- 14697736
TI  - Enzymatic digestion--a safe and rapid technique for individual separation of
      Macrobrachium rosenbergii embryos for cryopreservation studies.
AB  - A new, safe, and rapid technique for the individual separation of the embryos of
      giant freshwater prawn Macrobrachium rosenbergii de Man is described. Two
      protease enzymes, e.g., trypsin and collagenase were used. Embryos in the
      advanced stage of development (gray embryos with eyespot and heart beat) were
      selected for the study. Treatment with collagenase and trypsin at respective
      concentrations of 0.05 and 0.25% for 30 min resulted in 100% separation of 35-40
      mg of embryonic mass (approximately 180 embryos). A chelating agent, EDTA
      (ethylenediaminetetraacetic acid disodium salt: dihydrate) at 400 mg l(-1)
      enhanced the activity of trypsin. Trypsin and collagenase, when used together,
      were found to act synergistically. The separated embryos revealed no
      morphological injury when observed under the microscope. Further, in vitro
      hatching of the separated embryos was successful indicating that the present
      technique is safe and effective in achieving individual separation of prawn
      embryos.

PMID- 14697738
TI  - Primary immunodeficiencies: rare disorders in the era of global medicine.

PMID- 14697739
TI  - Particulate air pollutants and asthma. A paradigm for the role of oxidative
      stress in PM-induced adverse health effects.
AB  - Asthma is a chronic inflammatory disease, which involves a variety of different
      mediators, including reactive oxygen species. There is growing awareness that
      particulate pollutants act as adjuvants during allergic sensitization and can
      also induce acute asthma exacerbations. In this communication we review the role
      of oxidative stress in asthma, with an emphasis on the pro-oxidative effects of
      diesel exhaust particles and their chemicals in the respiratory tract. We review
      the biology of oxidative stress, including protective and injurious effects that
      explain the impact of particulate matter-induced oxidative stress in asthma.

PMID- 14697740
TI  - Curative effects of sodium fusidate on the development of dinitrobenzenesulfonic
      acid-induced colitis in rats.
AB  - Fusidic acid and sodium fusidate (fusidin) are antibiotics with low toxicity and
      powerful immunomodulatory activities in vitro and in vivo. In this study we have
      evaluated the effect of fusidin on the development of dinitrobenzenesulfonic acid
      (DNB)-induced colitis in rats that serves as a preclinical model of human
      inflammatory bowel disease (IBD). The data show that when administered orally at
      the dose of 80 (but not 40) mg/kg body wt under a "therapeutic" regimen soon
      after DNB application, fusidin significantly ameliorates clinical, histological,
      and seroimmunological signs of disease. These entailed a significant reduction in
      body weight loss, smaller increase in colon weights, milder macroscopic damage,
      and lower histological scores. In addition, when sacrificed at the end of the
      study, fusidin-treated rats had significantly lower blood levels of tumor
      necrosis factor alpha and interferon-gamma compared with untreated controls. The
      present findings concur with the beneficial actions of fusidin in a pilot study
      conducted in patients with Crohn's disease and warrant controlled studies in
      humans with IBD.

PMID- 14697741
TI  - An international study examining therapeutic options used in treatment of Wiskott
      Aldrich syndrome.
AB  - Wiskott-Aldrich syndrome is a rare immunodeficiency characterized by
      thrombocytopenia, eczema, recurrent infections, autoimmunity, and an increased
      incidence of malignancy. Clinical severity is highly variable. As a first step
      toward the development of therapeutic guidelines, an international study to
      evaluate current treatment strategies was undertaken. A total of 73 centers from
      24 countries participated. These centers provide care for 507 patients with
      Wiskott-Aldrich syndrome. Treatment strategies were strikingly variable in both
      small and large centers. Most options were used in at least some patients in the
      majority of centers, indicating that treatment is individualized; however, there
      were some clear trends. Most centers use intravenous gammaglobulin and
      prophylactic antibiotics in the majority of patients. Splenectomy was used more
      sparingly. Stem cell transplant was more likely to be used in centers providing
      care for 10 or more patients. Studies that better define prognostic markers and
      optimal therapy are needed.

PMID- 14697742
TI  - Specificity and immunochemical properties of anti-DNA antibodies induced in
      normal mice by immunization with mammalian DNA with a CpG oligonucleotide as
      adjuvant.
AB  - To elucidate the role of DNA antigen drive in the anti-DNA response, the
      specificity and immunochemical properties of anti-DNA antibodies induced in
      normal mice by immunization with double stranded (ds) mammalian DNA with a CpG
      oligonucleotide (ODN) adjuvant were characterized. Like spontaneous anti-DNA from
      MRL/lpr mice, the induced anti-DNA bound cross-reactively to DNA from five
      different species by ELISA. The induced antibodies displayed a predominance of
      IgG2a and had much lower amount of IgG3 than spontaneous antibodies. Surface
      plasmon resonance indicated that the induced and spontaneous anti-DNA antibodies
      have a similar range of avidity and binding kinetics. While sera from the MRL/lpr
      mice had substantial binding to histones and nucleosomes, the immunized mice had
      antibody levels to these antigens similar to those of mice treated only with
      incomplete Freund's adjuvant. Together, these results indicate that normal mice
      can produce autoantibodies to dsDNA, with a CpG ODN allowing the generation of
      antibodies resembling those in spontaneous autoimmunity.

PMID- 14697743
TI  - The immunosuppressive potential of misoprostol--efficacy and variability.
AB  - Existing evidence on the immunosuppressive efficacy of prostaglandin E (PGE) and
      its analogues in vivo is conflicting. We investigated the effect of misoprostol,
      an orally available PGE1 analogue, on T-cell proliferation, Th cell-derived
      cytokine production, and phagocytosis in healthy volunteers. All participants
      (n=20) received increasing doses of misoprostol (0-400 microg). Blood was drawn
      before and after intake. Misoprostol intake caused a time- and dose-dependent
      reduction of anti-CD3-stimulated cell proliferation. Whereas the synthesis of Th1
      cytokines (IL-2 and IFN-gamma) was dose-dependently reduced, IL-10 expression was
      increased at lower misoprostol doses. Concerning IL-4 expression, we observed an
      increased IL-4 production in males, but a decreased IL-4 production in females.
      Misoprostol intake also reduced phagocytosis activity in a dose-dependent manner.
      At least in part our results explain the immunosuppressive effects of misoprostol
      observed in vivo. The considerable interindividual variability as well as gender
      specific differences seem to account for the variability of clinical study
      results.

PMID- 14697744
TI  - Amelioration of graft versus host disease by galectin-1.
AB  - Graft versus host disease is a significant cause of morbidity and mortality
      following allogeneic hematopoietic stem cell transplantation. Galectin-1, a
      mammalian lectin that modulates T cell function and apoptosis, has been shown to
      be immunomodulatory in animal models of autoimmune disease. We investigated the
      efficacy of galectin-1 in a murine model of graft versus host disease and found
      that 68% of galectin-1-treated mice survived, compared to 3% of vehicle-treated
      mice. Galectin-1-treated animals also had reduced inflammatory infiltrates in
      tissues compared to animals treated with vehicle alone. Galectin-1 did not affect
      engraftment of donor hematopoietic cells. However, galectin-1-treated animals
      demonstrated increased cellularity in bone marrow and spleen with increased
      numbers of splenic B cells and CD4 T cells compared to those animals treated with
      vehicle alone. Galectin-1 treatment also significantly improved reconstitution of
      normal splenic architecture following transplant. Production of type I cytokines
      interleukin-2 (IL-2) and interferon-gamma was reduced in splenocytes derived from
      galectin-1-treated transplanted mice when compared to animals treated with
      vehicle alone, while production of the type II cytokines, IL-4 and IL-10, was
      similar between the two groups of animals. Although splenocytes from galectin-1
      treated transplanted animals responded to both third party antigens and leukemic
      challenge, host alloreactivity was significantly reduced when compared to cells
      from vehicle-treated animals. These results demonstrate that galectin-1 therapy
      is capable of increasing survival and suppressing the graft versus host immune
      response without compromising engraftment or immune reconstitution following
      allogeneic hematopoietic stem cell transplant.

PMID- 14697745
TI  - Severe phenotype of chronic granulomatous disease presenting in a female with a
      de novo mutation in gp91-phox and a non familial, extremely skewed X chromosome
      inactivation.
AB  - Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting
      from defects in the multienzyme complex NADPH-oxidase (phagozyte oxidase, phox),
      which normally produces microbicidal reactive oxygen metabolites (ROM). The
      reason for our patient's CGD was unusual, as revealed by the following in vitro
      findings in neutrophils and EBV-transformed B-cells: lack of flavocytochrome
      b(558) expression, restoration of significant ROM production after transduction
      with gp91-phox cDNA by a retrovirus vector, an 879G-->A, Trp289-->Stop mutation
      in one X chromosomal gp91-phox allele, a one-sided paternal X chromosome
      inactivation, as shown by a lyonization assay at the HUMARA locus, and the result
      of a dihydrorhodamine 123 flow cytometry assay revealing consistently that 1 in
      2500 neutrophils produced ROM at normal levels. Our conclusion: A presumed
      autosomal form of CGD has been excluded. Instead, a spontaneous mutation in gp91
      phox coinciding with an extreme X chromosome inactivation ratio resulted in X
      linked CGD in this young woman.

PMID- 14697746
TI  - Celiac disease-associated transglutaminase autoantibody target domains at
      diagnosis are age and sex dependent.
AB  - The contribution of age and/or sex to the transglutaminase (tTG) autoantibody
      response in celiac disease (CD) is not known. To gain insights into
      transglutaminase humoral autoimmunity at CD diagnosis, our aim was to
      characterize the autoimmune response against three tTG constructs [(full-length
      tTG(a.a.1-687), tTG(a.a.227-687), and tTG(a.a.473-687)] and to investigate into
      its relationship with CD patients' age and sex. One hundred seventy-five newly
      diagnosed CD patients (115 females and 60 males), subdivided into different
      groups according to age and sex, were studied using a serum 35S-radioimmunoassay.
      We found that among full-length tTG autoantibody-positive CD subjects (175/175),
      50.9% (89/175) and 83.4% (146/175) had autoantibodies against tTG(227-687) and
      tTG(473-687) domains, respectively. Female patients of less than 4 years
      expressed tTG(227-687)Abs in significantly higher percentage and mean
      autoantibody titers vs. all other groups investigated, and tTG(473-687)Abs in
      significantly higher titers with respect to adult female patients. Our data
      identify a subset of CD patients showing a strong humoral tTG immunoreactivity at
      diagnosis, thus suggesting that age and sex influence the anti-tTG autoantibody
      response.

PMID- 14697747
TI  - Prevalence of the chemokine receptor CCR5-Delta32 gene mutation in periodontal
      disease.
AB  - A 32-base-pair deletion in the CCR5 gene was previously shown to influence the
      susceptibility for several infectious diseases. The present study compared the
      frequency of the CCR5-Delta32 mutation among subjects with periodontal disease
      and healthy control individuals. The prevalence of the CCR5-Delta32 mutation was
      determined in 81 patients with generalized periodontitis and 121 healthy
      controls. Standardized clinical and radiographic criteria were used for the
      diagnosis of periodontitis for each subject. The CCR5-Delta32 mutation was
      identified by PCR amplification and subsequent agarose gel electrophoresis.
      Genotype and allele frequencies among both study groups were compared using
      Fisher's exact test at a level of significance of 5% (P<0.05). The frequency of
      the CCR5-Delta32 allele was 9.9% (16/162) for periodontitis patients and 10.7%
      (26/216) for the healthy controls. The allele frequencies between periodontitis
      patients and the control group for the CCR5-Delta32 mutation were not
      significantly different (P=0.801). The present study revealed no association
      between the CCR5-Delta32 mutation and susceptibility to periodontal disease.

PMID- 14697748
TI  - Different gender-associated genotype risks of Wegener's granulomatosis and
      microscopic polyangiitis.
AB  - Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are systemic
      small vessel vasculitides associated with ANCA (AAV). Predominant Th1 and Th2
      cytokine patterns have been reported for WG and MPA, respectively. Consequently,
      genotypes suppressing Th1 responses or augmenting Th2 responses may be more
      frequent in MPA than in WG. Transforming growth beta1 (TGF-beta1) and interleukin
      10 (IL-10) genes may modify the course of vasculitis. Therefore, we investigated
      associations between genotype frequencies of functional polymorphisms of these
      cytokine genes and clinical manifestations in AAV. One hundred sixty-one AAV
      patients and 153 healthy blood donors were genotyped for the biallelic
      polymorphism in codon 25 of the TGF-beta1 gene and the biallelic polymorphism at
      position -1082 of the IL-10 gene. No difference was found for TGF-beta1 codon 25
      polymorphism between control and patient groups. In contrast, a significant shift
      toward the homozygous AA genotype of the IL-10 (-1082) polymorphism was found in
      WG (25%, p<0.005) and MPA patients (39%; p<0.00001) compared to controls (10.5%).
      Furthermore, in MPA the AA homozygous genotype was significantly more frequent in
      females (62.5%) compared to males (20%, p<0.05). A contribution of the TGF-beta1
      codon 25 polymorphism to the susceptibility-defining genetic backgrounds of AAV
      appears unlikely. In contrast, our findings suggest a role of the enhanced IL-10
      (-1082) PM in WG and MPA with a significant gender difference in MPA.

PMID- 14697749
TI  - Immunophenotyping of blood lymphocytes at birth, during childhood, and during
      adulthood in HIV-1-uninfected Ethiopians.
AB  - To obtain more insight into blood lymphocyte subpopulations of Ethiopians, we
      studied the immunologic profile of children and neonates and compared these data
      with those obtained from adults. Peripheral blood mononuclear cells (PBMCs) and
      cord blood mononuclear cells (CBMCs) were collected from 137 HIV-1-uninfected
      subjects aged 0 (cord blood) up to 40 years. Lymphocyte subsets (T, B, and NK
      cells, CD4+ and CD8+ T cells) were determined and T cell activation (CD38 and HLA
      DR) and differentiation (CD45RO and CD27) markers were measured on CD4+ and CD8+
      T cells. The absolute number and percentage values of most lymphocyte
      subpopulations differed substantially with age. Neonates and children were found
      to have significantly higher CD4+ T cell counts compared to adults. The median
      absolute CD4 count at birth was comparable to those reported for Caucasians. At
      birth 97% of the CD4+ T cells were naive and this proportion significantly
      declined to 14.2% during adulthood. In addition, activation of both CD4+ and CD8+
      T cells, as determined by the double expression of HLA-DR and CD38, was observed
      in children under the age of 16 and adults, but not in neonates. A more
      differentiated phenotype (CD27-) was observed in adults compared to children for
      both CD4+ and CD8+ T cells. The immune alterations including the remarkably low
      CD4 count with highly depleted naive phenotype and a persistently activated
      immune system seen in adult Ethiopians are not apparent at birth, but rather
      develop over time.

PMID- 14697750
TI  - Regulatory effects of osteoprotegerin on cellular and humoral immune responses.
AB  - The interaction between receptor activator of nuclear factor-kappaB ligand
      (RANKL) and RANK has been reported to regulate immunity in addition to bone
      metabolism. The aim of this study was to determine if osteoprotegerin (OPG), an
      inhibitor of the RANKL-RANK interaction and possibly a new drug against
      osteoporosis, would adversely affect immunity. OPG was used to treat mice
      developing different models of cellular and humoral immune responses and also in
      vitro in T and B cell assays. In mice, OPG does not affect cell-mediated
      reactions such as contact hypersensitivity to the hapten oxazolone and liver
      damage, granuloma formation, and infectious load induced by mycobacterial
      infection. However, OPG increases humoral reactions such as the production of
      IgM, IgG, and IgE against the T cell dependent antigen keyhole limpet hemocyanin
      and the production of IgM against the T cell independent antigen Pneumovax. In
      vitro, OPG modestly co-stimulates T cells but does not affect the proliferation
      of B cells. OPG has modest immunoregulatory effects that seem to be confined to
      the humoral response to specific antigens.

PMID- 14697751
TI  - In vivo modulation of leukocyte trafficking receptor following therapeutic
      purging of myeloid cells: implications for treatment of HIV infection and other
      immune disorders.
AB  - Therapeutic purging of myeloid cells (monocytes and granulocytes) (MYP) has been
      proposed as a treatment of severe inflammatory conditions like ulcerative colitis
      and rheumatoid arthritis. Although direct purging of inflammatory cells
      contributes to its efficacy, the precise mechanism of action is still unclear. We
      have tested MYP in a pilot study on 12 patients with chronic HIV infection, of
      whom 6 underwent MYP. Three/6 MYP patients and none of the controls displayed a
      strong and long-lasting decrease of cells expressing CXCR3, a major chemokine
      receptor responsible for trafficking of inflammatory cells. In these three
      patients, the number of circulating CD4 T cells increased during treatment. The
      data provide a rational for the use of MYP as a therapeutic tool acting via the
      modulation of immune cell trafficking.

PMID- 14697752
TI  - Influenza vaccination and Guillain Barre syndrome.

PMID- 14697754
TI  - Abasic sites in DNA: repair and biological consequences in Saccharomyces
      cerevisiae.
AB  - Apurinic/apyrimidinic (AP) sites are one of the most frequent spontaneous lesions
      in DNA. They are potentially mutagenic and lethal lesions that can block DNA
      replication and transcription. In addition, cleavage of AP sites by AP
      endonucleases or AP lyases generates DNA single-strand breaks (SSBs) with 5'- or
      3'-blocked ends, respectively. Therefore, we suggest that AP sites and 3'- or 5'
      blocked SSBs, we name "honorary AP sites", constitute a single class of lesions.
      In this review, we describe the different mechanisms used by the budding yeast
      Saccharomyces cerevisiae to remove or tolerate AP sites and related SSBs. In wild
      type cells, AP sites are primarily repaired by the base excision repair (BER)
      pathway, with the nucleotide excision repair (NER) pathway as a back up activity.
      BER is initiated by one of the two AP endonucleases, Apn1 or Apn2. Three DNA N
      glycosylases/AP lyases, Ntg1, Ntg2 and Ogg1, can also incise AP sites in DNA.
      Rad27, a structure specific endonuclease, is involved in the repair of 5'-blocked
      ends, whereas Apn1, Apn2 and Rad1-Rad10 are involved in the removal of 3'-blocked
      ends using their 3'-phosphodiesterase and 3'-flap endonuclease activities,
      respectively. AP sites can stall DNA replication forks, as well as they block in
      vitro DNA synthesis by DNA polymerase delta. Restart of stalled forks can occur
      through a recombination-associated pathway initiated by the Mus81-Mms4
      endonuclease or mutagenic translesion DNA synthesis (TLS). The mutagenic bypass
      of AP sites is a two-polymerases affair with an inserter DNA polymerase
      (Poldelta, Poleta or Rev1) and an extender DNA polymerase (Polzeta). Under normal
      growth conditions, inactivation of Apn1, Apn2 and Rad1-Rad10 causes cell death.
      Therefore, the burden of spontaneous AP sites is not compatible with life, in the
      absence of excision repair pathways. These results in yeast demonstrate that AP
      sites are critical endogenous DNA damages that cause genetic instability and by
      analogy could be associated with degenerative pathologies in human.

PMID- 14697755
TI  - High G/C content of cohesive overhangs renders DNA end joining Ku-independent.
AB  - Ku plays an important role in the repair of double strand DNA breaks by non
      homologous DNA end joining (NHEJ). Ku is thought to exert its function by
      aligning the two DNA ends. A previous study showed that the joining of certain
      cohesive DNA ends in cell-free in vitro reactions was independent of Ku [Mol.
      Cell. Biol. 19 (1999) 2585]. To investigate a possible correlation between Ku
      dependence of DNA end joining reactions and the strength of base pair
      interactions between cohesive ends, we constructed a series of repair substrates
      with either 3'- or 5'-overhangs, which consisted entirely of either A/T or G/C
      residues. We found that after Ku-immunodepletion of the extract, the joining of
      cohesive ends that associate by the formation of four A:T base pairs was reduced,
      while the joining of ends that associate through four G:C base pairs was
      unaffected or slightly stimulated. The precision of the repair was not reduced in
      Ku-independent reactions. Our results indicate that the requirement for Ku is
      dependent on how stably the two cohesive DNA ends can associate by base-pairing.
      Two independent assays for protein-DNA interactions did not reveal any
      differences in Ku binding to substrates with A/T and G/C overhangs, suggesting
      that in this system Ku is recruited to the repair site regardless of whether it
      is functionally required or not. The finding that Ku is dispensable for efficient
      and precise joining of ends with cohesive G/C overhangs also suggests that
      alignment of DNA ends may be the sole function of Ku during NHEJ.

PMID- 14697756
TI  - Orchestration of base excision repair by controlling the rates of enzymatic
      activities.
AB  - Base excision repair (BER) is one of the major pathways for repair of simple DNA
      base lesions and is carried out through a series of coordinated reactions relying
      on several different enzymatic activities and accessory proteins. Imbalance of
      BER activities has been reported to be linked to genetic instability and cancer.
      To experimentally address the mechanisms orchestrating BER, we monitored both the
      overall rate and the rate-limiting steps in the repair in cell-free extracts of
      five different endogenously occurring DNA lesions (abasic site, uracil, 8
      oxoguanine, hypoxanthine and 5,6-dihydrouracil) and the effect of addition of
      rate-limiting BER components on the rate and co-ordination of BER reactions. We
      find that several mechanisms including regulation of DNA glycosylase turnover and
      involvement of poly(ADP-ribose) polymerase participate in synchronization of the
      repair events. We also find that repair of different DNA lesions involves
      different mechanisms for optimizing repair rates without accumulation of
      intermediates. Repair of some lesions such as 8-oxoguanine is regulated by
      glycosylase turnover and progress without substantial accumulation of repair
      intermediates. However, during repair of the apurinic/apyrimidinic (AP) sites or
      5,6-dihydrouracil, poly(ADP-ribose) polymerase plays an important role in the
      coordination of the rates of repair reactions.

PMID- 14697757
TI  - Identification of DNA-PK in the arthropods. Evidence for the ancient ancestry of
      vertebrate non-homologous end-joining.
AB  - Cellular life depends upon the preservation and transmission of genetic material.
      Double stranded DNA breaks (DSBs) cause catastrophic gene loss in cell division
      and must be promptly and accurately repaired. In eukaryotes DSBs may be repaired
      by either non-homologous end-joining (NHEJ), single strand annealing or
      homologous recombination (HR). Vertebrate NHEJ has been shown to depend upon the
      DNA-dependent protein kinase (DNA-PK) consisting of the phosphatidylinositol 3
      (PI 3)-kinase like (PIKK) catalytic sub-unit (DNA-PKcs) and the DNA targeting
      factor Ku. Our analysis of recently completed genomes found several novel PIKKs
      in Anopheles gambiae and Drosophila melanogaster including a novel mosquito DNA
      PKcs orthologue, the first non-vertebrate DNA-PKcs described to date. We also
      detected a DNA-PKcs fragment in the high quality EST set of Apis mellifera
      ligustica (honey bee) suggesting that DNA-PK is a far older and more important
      eukaryotic complex than previously thought.

PMID- 14697758
TI  - End-joining of blunt DNA double-strand breaks in mammalian fibroblasts is precise
      and requires DNA-PK and XRCC4.
AB  - DNA double-strand break repair by non-homologous end-joining (NHEJ) is generally
      considered to be an imprecise repair pathway. In order to study repair of a
      blunt, 5' phosphorylated break in the DNA of mammalian fibroblasts, we used the
      E. coli cut-and-paste type transposon Tn5. We found that the Tn5 transposase can
      mediate transposon excision in Chinese hamster cell lines. Interestingly, a blunt
      5' phosphorylated break could efficiently be repaired without loss of nucleotides
      in wild type fibroblasts. Catalytic subunit of DNA-dependent protein kinase (DNA
      PK(CS)) deficiency reduced the efficiency of joining four-fold without reducing
      precision, whereas both efficiency and accuracy of joining were affected in Ku80
      or XRCC4 mutant cell lines. These results show that both the DNA-PK and the
      XRCC4/ligase IV complexes are required for NHEJ and that other, more error-prone,
      repair processes cannot efficiently substitute for joining of blunt breaks
      produced in living cells. Interestingly, the severity of the end-joining defect
      differs between the various mutants, which may explain the difference in the
      severity of the phenotypes, which have been observed in the corresponding mouse
      models.

PMID- 14697760
TI  - RecA mediated initial alignment of homologous DNA molecules displays apparent
      first order kinetics with little effect of heterology.
AB  - The mechanism and determinants of RecA mediated initial alignment of homologous
      DNA molecules were studied by performing Monte Carlo simulations of the dynamics
      of DNA molecules. The simulation procedure was used to assess the effect of
      heterologous DNA and dilution on the rate of formation and yield of homologous
      alignments. The results show that the apparent first order kinetic behavior and
      the impact of heterologous DNA, reported in literature [J. Biol. Chem. 261 (1986)
      1025], can be observed even if the conversion of the initially aligned molecules
      into a stable joint is not rate-determining. The present study is the first step
      towards developing rigorous computational models to describe the process of
      homologous recombination, and theoretical frameworks to retrieve biophysical
      parameters of strand pairing and exchange proteins from in vitro assays of joint
      molecule formation.

PMID- 14697759
TI  - Involvement of two endonuclease III homologs in the base excision repair pathway
      for the processing of DNA alkylation damage in Saccharomyces cerevisiae.
AB  - DNA base excision repair (BER) is initiated by DNA glycosylases that recognize
      and remove damaged bases. The phosphate backbone adjacent to the resulting
      apurinic/apyrimidinic (AP) site is then cleaved by an AP endonuclease or
      glycosylase-associated AP lyase to invoke subsequent BER steps. We have used a
      genetic approach in Saccharomyces cerevisiae to determine whether or not AP sites
      are blocks to DNA replication and the biological consequences if AP sites persist
      in the genome. We previously reported that yeast cells deficient in the two AP
      endonucleases (apn1 apn2 double mutant) are extremely sensitive to killing by a
      model DNA alkylating agent methyl methanesulfonate (MMS) and that this
      sensitivity can be reduced by deleting the MAG1 3-methyladenine DNA glycosylase
      gene. Here we report that in the absence of the AP endonucleases, deletion of two
      Escherichia coli endonuclease III homologs, NTG1 and NTG2, partially suppresses
      MMS-induced killing, which indicates that the AP lyase products are deleterious
      unless they are further processed by an AP endonuclease. The severe MMS
      sensitivity seen in AP endonuclease deficient strains can also be rescued by
      treatment of cells with the AP lyase inhibitor methoxyamine, which suggests that
      the product of AP lyase action on an AP site is indeed an extremely toxic lesion.
      In addition to the AP endonuclease interactions, deletion of NTG1 and NTG2
      enhances the mag1 mutant sensitivity to MMS, whereas overexpression of MAG1 in
      either the ntg1 or ntg2 mutant severely affects cell growth. These results help
      to delineate alkylation base lesion flow within the BER pathway.

PMID- 14697761
TI  - Kinetic analysis of the nicking and hairpin formation steps in V(D)J
      recombination.
AB  - The complete cleavage phase of V(D)J recombination includes four phases: binding
      of the active RAG complexes to the 12- or 23-signals, nicking of the signals,
      synapsis of the two signals, and hairpin formation at both signals concurrently.
      We have done time courses for the complete cleavage phase of the V(D)J
      recombination reaction and quantitated the amount of active RAG enzyme. We have
      also formulated a kinetic model for the binding, nicking, synapsis, and hairpin
      formation phases. We have utilized free solution enzymatic measurements for the
      binding and nicking phases as we do mathematical simulations of the kinetic
      model. This permits iteration of rate constants for the synapsis and hairpin
      formation phases until the model fits the observed overall cleavage time course.
      This process yields a rate constant for the hairpin formation that is 0.004 min(
      1), which corresponds to an average catalytic cycle time of 250 min. This value
      is exceedingly close to a measured value of this constant that relied on wash-out
      of an inhibitory cofactor. The agreement indicates that this is likely to be the
      rate of the hairpin step over a wide range of range of conditions and
      irrespective of the DNA sequence of the V, D or J coding end located adjacent to
      the signal. These findings indicate that, under optimal in vitro conditions, the
      core RAG proteins carry out nicking at a rate which is nearly 150-fold faster
      than hairpin formation. The physiologic implications of this and other kinetic
      inferences of these time courses are discussed.

PMID- 14697762
TI  - Multiple TPR motifs characterize the Fanconi anemia FANCG protein.
AB  - The genome protection pathway that is defective in patients with Fanconi anemia
      (FA) is controlled by at least eight genes, including BRCA2. A key step in the
      pathway involves the monoubiquitylation of FANCD2, which critically depends on a
      multi-subunit nuclear 'core complex' of at least six FANC proteins (FANCA, -C, 
      E, -F, -G, and -L). Except for FANCL, which has WD40 repeats and a RING finger
      domain, no significant domain structure has so far been recognized in any of the
      core complex proteins. By using a homology search strategy comparing the human
      FANCG protein sequence with its ortholog sequences in Oryzias latipes (Japanese
      rice fish) and Danio rerio (zebrafish) we identified at least seven
      tetratricopeptide repeat motifs (TPRs) covering a major part of this protein.
      TPRs are degenerate 34-amino acid repeat motifs which function as scaffolds
      mediating protein-protein interactions, often found in multiprotein complexes. In
      four out of five TPR motifs tested (TPR1, -2, -5, and -6), targeted missense
      mutagenesis disrupting the motifs at the critical position 8 of each TPR caused
      complete or partial loss of FANCG function. Loss of function was evident from
      failure of the mutant proteins to complement the cellular FA phenotype in FA-G
      lymphoblasts, which was correlated with loss of binding to FANCA. Although the
      TPR4 mutant fully complemented the cells, it showed a reduced interaction with
      FANCA, suggesting that this TPR may also be of functional importance. The
      recognition of FANCG as a typical TPR protein predicts this protein to play a key
      role in the assembly and/or stabilization of the nuclear FA protein core complex.

PMID- 14697763
TI  - DNA-cytosine deaminases: from antibody maturation to antiviral defense.
AB  - The deamination of cytosines in DNA to uracil, thought to be initiated by free
      water within the cells, is a well studied pathway by which C to T mutations
      occur. Until recently, this conversion was frequently referred to as being
      spontaneous because of the involvement of cellular water. The recent discovery of
      a family of enzymes in mammalian cells that catalyze this reaction was unexpected
      and has created excitement in at least two areas of biology, immunology and
      virology. One of these enzymes, activation-induced cytidine deaminase (AID), is
      required for the final steps in the maturation of antibodies. The key features of
      this process include the introduction of a wide variety of base substitutions in
      the immunoglobulin genes and the creation of region-specific double-strand
      breaks. Another member of this family, Apobec3G, is involved in the mutational
      inactivation and degradation of the human immunodeficiency virus (HIV-1). Among
      the many intriguing features of these processes is the likely involvement of the
      enzyme that is thought to "protect" cellular DNA against the accumulation of
      uracils, uracil-DNA glycosylase (UDG). It appears that in certain situations, the
      newly discovered DNA-cytosine deaminases can team up with UDG to extensively
      mutate and degrade DNA. This article discusses the many questions raised
      regarding the role of these enzymes in protecting cells against infections, and
      about their possible roles in genome evolution and carcinogenesis.

PMID- 14697764
TI  - Excision repair--the first steps into mammalian cells. 1968.

PMID- 14697765
TI  - Discovery of novel modulators of metabotropic glutamate receptor subtype-5.
AB  - A series of potent and selective mGluR5 antagonists were synthesized and
      evaluated in vitro and in vivo. It was found that a pyridyl functionality is a
      potential replacement for acetonitrile in the lead structure, with 2-pyridyl
      being most favored. Additionally, the benzoxazole moiety could also be replaced
      by other heterobicyclic rings such as imidazothiazole.

PMID- 14697766
TI  - A transesterification reaction is implicated in the covalent binding of
      benzo[b]acronycine anticancer agents with DNA and glutathion.
AB  - The benzo[b]acronycine derivative S23906-1 has been recently identified as a
      promising antitumor agent, showing remarkable in vivo activities against a panel
      of solid tumors. The anticancer activity is attributed to the capacity of the
      drug to alkylate DNA, selectively at the exocyclic 2-amino group of guanine
      residues. Hydrolysis of the C-1 and C-2 acetate groups of S23906-1 provides the
      diol compound S28907-1 which is inactive whereas the intermediate C-2 monoacetate
      derivative S28687-1 is both highly reactive toward DNA and cytotoxic. The
      reactivity of this later compound S28687-1 toward two bionucleophiles, DNA and
      the tripeptide glutathion, has been investigated by mass spectrometry to identify
      the nature of the (type II) covalent adducts characterized by the loss of the
      acetate group at position 2. On the basis of NMR and molecular modeling analyses,
      the reaction mechanism is explained by a transesterification process where the
      acetate leaving group is transferred from position C-2 to C-1. Altogether, the
      study validates the reaction scheme of benzo[b]acronycine derivative with its
      target.

PMID- 14697767
TI  - Occurrence of antioxidant and radical scavenging proanthocyanidins from the
      Indian minor spice nagkesar (Mammea longifolia planch and triana syn).
AB  - Nagkesar (buds of Mammea longifolia) is extensively used in culinary preparations
      especially in spice blend in India. Previously thirteen compounds were identified
      from the medium polar fractions of methanol extract of buds of M. longifolia. In
      continuation of the study, the polar fraction of methanol extract exhibited
      stronger antioxidative and radical scavenging activities. An attempt was made to
      separate and identify the active compounds and found that those were
      proanthocyanidin oligomers with mean degree of polymerisation ranges from 2 to
      10. This is the first report to indicate that Mammea buds contain antioxidant and
      radical scavenging procyanidin oligomers.

PMID- 14697768
TI  - Structure-activity relationships by mass spectrometry: identification of novel
      MMP-3 inhibitors.
AB  - A novel class of nonpeptide inhibitors of stromelysin (MMP-3) has been discovered
      with the use of mass spectrometry. The method relies on the development of
      structure-activity relationships by mass spectrometry (SAR by MS) and utilizes
      information derived from the binding of known inhibitors to identify novel
      inhibitors of a target protein with a minimum of synthetic effort. Noncovalent
      complexes of known inhibitors with a target protein are analyzed; these
      inhibitors are deconstructed into sets of fragments which compete for common or
      overlapping binding sites on the target protein. The binding of each fragment set
      can be studied independently. With the use of competition studies, novel members
      of each fragment set are identified from compound libraries that bind to the same
      site on the target protein. A novel inhibitor of the target protein was then
      constructed by chemically linking a combination of members of each fragment set
      in a manner guided by the proximity and orientation of the fragments derived from
      the known inhibitors. In the case of stromelysin, a novel inhibitor composed of
      favorably linked fragments was observed to form a 1:1 complex with stromelysin.
      Compounds that were not linked appropriately formed higher order complexes with
      stoichiometries of 2:1 or greater. These linked molecules were subsequently
      assessed for their ability to block stromelysin function in a chromogenic
      substrate assay.

PMID- 14697769
TI  - (3Z)-2-Acetylamino-3-octadecen-1-ol as a potent apoptotic agent against HL-60
      cells.
AB  - (2R,3Z)-, (2R,3E)-, (2S,3Z) and (2S,3E)-2-Acetylamino-3-octadecen-1-ol, and (2R)-
      and (2S)-2-acetylamino-octadecan-1-ol were prepared using the Wittig olefination
      of Garner's aldehyde (N-Boc-N,O-isopropylidene-L- or D-serinal) from L- or D
      serine. The apoptotic activities of these saturated and unsaturated 2
      acetylaminoalcohols were examined in human leukemia HL-60 cells using MTT assay.
      Among the newly synthesized compounds, the cis-isomers were the most potent.
      Despite their simple structures, (2R,3Z)- and (2S,3Z)-2-acetylamino-3-octadecen-1
      ol showed high and comparable apoptotic activities compared with N-acetyl-D
      erythro-sphingosine (D-e-C2-Cer, a well-known inducer of apoptosis). Their
      apoptotic activities were in the order D-e-C2-Cer approximately L-e-C2-Cer
      approximately (2R,3Z)- approximately (2S,3Z)->>(2R,3E)- approximately (2S,3E)-
      approximately (2R)- approximately (2S)-derivative. Qualitative analysis of DNA
      fragmentation caused by these compounds was conducted using agarose gel
      electrophoresis, and typical DNA fragmentation was found in the cases of (2R,3Z)-
      and (2S,3Z)-isomers such as C2-Cer, but not trans and saturated isomers. The
      morphological features of the cells, the proteolytic processing of pro-caspase-3,
      and the cleavage of PARP as a result of exogenous treatment with (2R,3Z)- and
      (2S,3Z)-isomers indicated that cell death induced by these compounds was
      apoptosis. These observations suggest that these newly synthesized compounds,
      (3Z)-2-Acetylamino-3-octadecen-1-ol, have similar characteristics and apoptosis
      inducing activities against HL-60 cells with C2-Cer.

PMID- 14697770
TI  - DNA sequence-specific recognition of peptides incorporating the HPRK and
      polyamide motifs.
AB  - Three peptide amides, HPRK(Py)(4)HPRK-NH(2) (PyH-12), HPRK(Py)(3)HPRK-NH(2) (PyH
      11) and HPRK(Py)(2)HPRK-NH(2) (PyH-10), incorporating two HPRK motifs and various
      4-amino-1-methylpyrrole-2-carboxylic acid residues (Py) were synthesized by solid
      phase peptide methodology. The binding of these three peptides to a 5'-32P
      labeled 158-mer DNA duplex (Watson fragment) and to a 5'-32P-labeled 135-mer DNA
      duplex (complementary Crick fragment) was investigated by quantitative DNase I
      footprinting. On the 158-mer Watson strand, the most distinctive DNase I
      blockages seen with all three peptides occur around positions 105-112 and 76-79,
      corresponding to the sequences 5'-GAGAAAAT-3' and 5'-CGGT-3', respectively.
      However, on the complementary Crick strand, only PyH-12 strongly discriminates
      the 5'-TTT-3' site around positions 108-110 whereas both PyH-11 and PyH-10 have
      moderate binding around positions 102-112 comprising the sequence 5'-ATTTTCTCCTT
      3'. Possible bidentate and single interactions of the side-chain functions and
      alpha-amino protons of the peptides with DNA bases are discussed.

PMID- 14697771
TI  - Pharmacophore identification and 3D-QSAR studies in N-(2-benzoyl phenyl)-L
      tyrosines as PPAR gamma agonists.
AB  - The identification of pharmacophore and three dimensional quantitative structure
      activity studies have been performed on a set of N-(2-Benzoylphenyl)-L-tyrosine
      for their PPARgamma agonist activity by using the logico-structural based
      software Apex 3D-which describes the properties and distribution of primary and
      secondary biophore sites in the three dimensional space. Among several models,
      two models of comparable probability were selected on the basis of R(2)>0.60,
      chance </=0.04, size <4, match >0.20. These models showed a good correlation
      between the observed and predicted biological activity both for training and test
      sets.

PMID- 14697773
TI  - Quantitative structure-activity relationship in aziridinyl-1,4-naphthoquinone
      antimalarials: study of theoretical correlations by the PM3 method.
AB  - Several molecular parameters for 2,3,5-substituted 1,4-naphthoquinones including
      2-aziridinyl and 2,3-aziridinyl-1,4-naphthoquinones with antimalarial activities
      were obtained with the semi-empirical PM3 method. The descriptor related to the
      Gibbs free energy of an isodesmic equation defining the reduction of the
      naphthoquinones was found to have high correlation with activity. The
      quantitative models reported clearly show a dependence of activity on the redox
      potential for reduction of the naphthoquinones. Compounds with lower values of
      DeltaG for reduction are more active than those with higher values of DeltaG.

PMID- 14697772
TI  - Structure-activity relationship studies on unifiram (DM232) and sunifiram
      (DM235), two novel and potent cognition enhancing drugs.
AB  - Structure-activity relationships on two novel potent cognition enhancing drugs,
      unifiram (DM232, 1) and sunifiram (DM235, 2), are reported. Although none of the
      compounds synthesised reached the potency of the parent drugs, some fairly active
      compounds have been identified that may represent new leads to develop other
      cognition enhancing drugs. An interesting result of this research is the
      identification of two compounds (13 and 14) that are endowed with amnesing
      activity (the opposite of the activity of the original molecules) and are nearly
      equipotent to scopolamine. Moreover, two compounds of the series (5 and 6) were
      found endowed with analgesic activity on a rat model of neuropathic pain at the
      dose of 1 mg/kg.

PMID- 14697774
TI  - 11C-Fallypride: radiosynthesis and preliminary evaluation of a novel dopamine
      D2/D3 receptor PET radiotracer in non-human primate brain.
AB  - Fallypride [benzamide, 5-(3-fluoropropyl)-2,3-dimethoxy-N-[(2S)-1-(2-propenyl)-2
      pyrrolidinyl]methyl]-, CAS RN 166173-78-0] is a selective dopamine D2/D3 receptor
      antagonist. Carbon-11 labeled fallypride may serve as a radiotracer for use in
      biomedical imaging technique positron emission tomography (PET). The precursor, 5
      (3-fluoropropyl)-2-hydroxy-3-methoxy-N-[(2S)-1-(2-propenyl)-2
      pyrrolidinyl]methyl]benzamide was synthesized from 2-hydroxy-3-methoxy-5-(2
      propenyl)benzoic acid, methyl ester in seven steps with approximately 10% overall
      chemical yield. Using this precursor (11)C-fallypride was produced by
      radiolabeling with (11)C-methyl iodide in 25-40% radiochemical yields with
      specific activities of 200-1000 Ci/mmol. PET imaging studies in nonhuman primates
      with (11)C-fallypride showed radiotracer localization in dopaminergic brain
      regions such as caudate, putamen, thalamus and cortex. This regional localization
      of (11)C-fallypride is similar to that observed previously for (18)F-fallypride.
      The results suggest (11)C-fallypride is a useful PET radiotracer for imaging
      dopamine D2/D3 receptors.

PMID- 14697775
TI  - Synthesis and antiviral evaluation of benzimidazoles, quinoxalines and indoles
      from dehydroabietic acid.
AB  - Several heterocycles, such as benzimidazoles, quinoxalines and indoles
      incorporated into a hydrophenanthrene and naphthalene skeleton, were synthesised
      from two useful ortho-bromonitro precursors derived from dehydroabietic acid:
      methyl 12-bromo-13-nitro-deisopropyldehydroabietate and methyl 12-bromo-13,14
      dinitro-deisopropyldehydroabietate. The new heterocycles were evaluated for their
      activity in vitro against several RNA and DNA viruses.

PMID- 14697776
TI  - Analogues of FAUC 73 revealing new insights into the structural requirements of
      nonaromatic dopamine D3 receptor agonists.
AB  - Employing the nonaromatic D3 agonist FAUC 73 as a lead compound, the dopaminergic
      enynes 1a,b and the diene 2 (FAUC 206) were synthesized via palladium-catalyzed
      cross-coupling. FAUC 206 showed remarkable D3 affinity and enhanced selectivity
      over D4 when compared to the lead compound. To learn more about the bioactive
      structure of the diene moiety, computational studies including DFT-based
      conformational analysis and calculations of the magnetic shielding properties
      were performed. The electrostatic properties of the pharmacophoric pi-systems
      were visualized by diagnostic MEP maps.

PMID- 14697777
TI  - Erythrocyte membrane modifying agents and the inhibition of Plasmodium falciparum
      growth: structure-activity relationships for betulinic acid analogues.
AB  - The natural triterpene betulinic acid and its analogues (betulinic aldehyde,
      lupeol, betulin, methyl betulinate and betulinic acid amide) caused concentration
      dependent alterations of erythrocyte membrane shape towards stomatocytes or
      echinocytes according to their hydrogen bonding properties. Thus, the analogues
      with a functional group having a capacity of donating a hydrogen bond (COOH,
      CH(2)OH, CONH(2)) caused formation of echinocytes, whereas those lacking this
      ability (CH(3), CHO, COOCH(3)) induced formation of stomatocytes. Both kinds of
      erythrocyte alterations were prohibitive with respect to Plasmodium falciparum
      invasion and growth; all compounds were inhibitory with IC(50) values in the
      range 7-28 microM, and the growth inhibition correlated well with the extent of
      membrane curvature changes assessed by transmission electron microscopy.
      Erythrocytes pre-loaded with betulinic acid or its analogues and extensively
      washed in order to remove excess of the chemicals could not serve as hosts for P.
      falciparum parasites. Betulinic acid and congeners can be responsible for in
      vitro antiplasmodial activity of plant extracts, as shown for Zataria multiflora
      Boiss. (Labiatae) and Zizyphus vulgaris Lam. (Rhamnaceae). The activity is
      evidently due to the incorporation of the compounds into the lipid bilayer of
      erythrocytes, and may be caused by modifications of cholesterol-rich membrane
      rafts, recently shown to play an important role in parasite vacuolization. The
      established link between erythrocyte membrane modifications and antiplasmodial
      activity may provide a novel target for potential antimalarial drugs.

PMID- 14697778
TI  - Synthesis and evaluation of N1/C4-substituted beta-lactams as PPE and HLE
      inhibitors.
AB  - 4-(Alkylamino)carbonyl-1-(alkoxy)carbonyl-2-azetidinones (9-11) have been
      prepared in five steps from 4-(benzyloxy)carbonyl-1-(t-butyldimethyl)silyl-2
      azetidinone (1). The beta-lactam reactivity of 9 has been established by 1H NMR
      experiment. Compound 11 was a good reversible inhibitor of PPE and HLE. Based on
      theoretical design, series of 2-azetidinones (12-17) and 4-(alkoxy)carbonyl-2
      azetidinones (18-21) bearing various carbonyl (ester, thiolester, amide) and
      thiocarbonyl (thioamide) functionalities at position N1 were similarly prepared.
      In the absence of C4-substituent, the compounds were inactive against elastases.
      On the other hand, 4-(benzyloxy)carbonyl-1-(ethylthioxy)carbonyl-2-azetidinone
      (19) and 4-(benzyloxy)carbonyl-1-(benzylamino)thiocarbonyl-2-azetidinone (21)
      were both good reversible inhibitors, but acting most probably via different
      mechanisms (enzymic processing of the exocyclic ester function or beta-lactam
      ring opening).

PMID- 14697779
TI  - Synthesis and biological evaluation of disubstituted N6-cyclopentyladenine
      analogues: the search for a neutral antagonist with high affinity for the
      adenosine A1 receptor.
AB  - Novel 3,8- and 8,9-disubstituted N(6)-cyclopentyladenine derivatives were
      synthesised in moderate overall yield from 6-chloropurine. The derivatives were
      made in an attempt to find a new neutral antagonist with high affinity for
      adenosine A(1) receptors. N(6)-Cyclopentyl-9-methyladenine (N-0840) was used as a
      lead compound. Binding affinities of the new analogues were determined for human
      adenosine A(1) and A(3) receptors. Their intrinsic activity was assessed in
      [35S]GTPgammaS binding experiments. Elongation of the 9-methyl of N-0840 to a 9
      propyl substituent was very well tolerated. A 9-benzyl group, on the other hand,
      caused a decrease in adenosine A(1) receptor affinity. Next, the 8-position was
      examined in detail, and affinity was increased with appropriate substitution.
      Most derivatives were A(1)-selective and 20 of the new compounds (6-9, 15-21, 23
      26, 28, 31, 33, 35, and 36) had higher adenosine A(1) receptor affinity than the
      reference substance, N-0840. Compound 31 (N(6)-cyclopentyl-8-(N
      methylisopropylamino)-9-methyladenine, LUF 5608) had the highest adenosine A(1)
      receptor affinity, 7.7 nM. In the [35S]GTPgammaS binding experiments, derivatives
      5, 14, 22, 23, 25, 26, 33 and 34 did not significantly change basal
      [35S]GTPgammaS binding, thus behaving as neutral antagonists. Moreover, four of
      these compounds (23, 25, 26, and 33) displayed a 4- to 10-fold increased
      adenosine A(1) receptor affinity (75-206 nM) compared to N-0840 (852 nM). In
      summary, we synthesised a range of N-0840 analogues with higher affinity for
      adenosine A(1) receptors. In addition, four new derivatives, LUF 5666 (23), LUF
      5668 (25), LUF 5669 (26) and LUF 5674 (33), behaved as neutral antagonists when
      tested in [35S]GTPgammaS binding studies. Thus, these compounds have improved
      characteristics as neutral adenosine A(1) receptor antagonists.

PMID- 14697780
TI  - Interactions between 1-benzoyl-4-p-chlorophenyl thiosemicarbazide and serum
      albumin: investigation by fluorescence spectroscopy.
AB  - The interactions between 1-benzoyl-4-p-chlorphenyl thiosemicarbazide (BCPT) and
      bovine serum albumin (BSA) or human serum albumin (HSA) have been studied by
      fluorescence spectroscopy. By the analysis of fluorescence spectrum and
      fluorescence intensity, it was showed that BCPT has a strong ability to quench
      the intrinsic fluorescence of both bovine serum albumin and human serum albumin
      through a static quenching procedure. The binding constants of BCPT with BSA or
      HSA were determined at different temperatures based on the fluorescence quenching
      results. The binding sites were obtained and the binding force were suggested to
      be mainly hydrophobic. The effect of common ions on the binding constants was
      also investigated. A new fluorescence spectroscopy assay of the proteins is
      presented. The linear range is 5.36-67.0 microg mL(-1) with recovery of 101.1%
      for BSA, and the linear range is 8.28-144.9 microg mL(-1) with recovery of 102.6%
      for HSA. Determination of the proteins in bovine serum or in human serum by this
      method gives results which are very close to those obtained by using Coomassie
      Brilliant Blue G-250 colorimetry. A practical method was proposed for the
      determination of BCPT in human serum samples.

PMID- 14697781
TI  - Water-soluble prodrugs of dipeptide HIV protease inhibitors based on O-->N
      intramolecular acyl migration: Design, synthesis and kinetic study.
AB  - To improve the low water-solubility of HIV protease inhibitors, we synthesized
      water-soluble prodrugs of KNI-727, a potent small-sized dipeptide-type HIV-1
      protease inhibitor consisting of an Apns-Dmt core (Apns; allophenylnorstatine,
      Dmt; (R)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid) as inhibitory
      machinery. These prodrugs contained an O-acyl peptidomimetic structure with an
      ionized amino group leading to an increase in water-solubility, and were designed
      to regenerate the corresponding parent drugs based on the O-->N intramolecular
      acyl migration reaction via a five-membered ring intermediate at the alpha
      hydroxy-beta-amino acid residue, that is Apns. The synthetic prodrug 3a improved
      the water-solubility (13 mg/mL) more than 8000-fold in comparison with the parent
      compound, which is the practically acceptable value as water-soluble drug.
      Furthermore, to understand the structural effects of the O-acyl moiety on the
      migration rate, we evaluated several phenylacetyl-type and benzoyl-type prodrugs.
      These prodrugs were stable as an HCl salt and in a strongly acidic solution
      corresponding to gastric juice (pH 2.0), and could be converted to the parent
      compounds promptly under aqueous conditions from slightly acidic to basic pH at
      37 degrees C.

PMID- 14697782
TI  - DFT-based QSAR study of testosterone and its derivatives.
AB  - QSAR study of derivatives of testosterone has been made with the help of quantum
      mechanical parameters such as Absolute Hardness (eta) and Electronegativity
      (chi). These two parameters have been derived with the help of density functional
      theory. The 3-D modeling and geometry optimization of all the compounds have been
      done with the help of PCMODEL software and semiempirical PM3 calculations
      performed with the help of WinMOPAC-7.21 software. The absolute hardness provides
      valuable information due to maximum hardness principle and used in development of
      QSAR. The information provided by electronegativity is not as clear as in case of
      absolute hardness.

PMID- 14697783
TI  - Homoepiboxidines: further potent agonists for nicotinic receptors.
AB  - Homoepiboxidine (3) and the corresponding N-methyl (4) and N-benzyl (5)
      derivatives were prepared from a 6beta-carbomethoxynortropane (8). Affinities and
      functional activities at neuromuscular, central neuronal and ganglionic-type
      nicotinic receptors were compared to those of epibatidine 1, and epiboxidine 2.
      Homoepiboxidine had equivalent affinity/activity to epiboxidine at neuromuscular,
      neuronal alpha4beta2, and most alpha3-containing ganglionic-type nicotinic
      receptors. The N-substituted derivatives showed reduced affinity/activity at most
      receptor subtypes. Replacement of the methylisoxazole moiety of 3 and 4 with a
      methyloxadiazole moiety provided analogues 6 and 7, which had greatly reduced
      affinity/activity in virtually all assays at nicotinic receptors. Marked
      analgetic activity in mice occurred at the following ip doses: epibatidine 10
      microg/kg; epiboxidine 25 microg/kg; homoepiboxidine 100 microg/kg; N
      methylhomoepiboxidine 100 microg/kg; the methyloxadiazole (6) 100 microg/kg. The
      time course at such ip doses was significantly longer for homoepiboxidine 3 with
      marked analgesia still manifest at 30 min post-injection. Epiboxidine and the
      homoepiboxidines were less toxic than epibatidine.

PMID- 14697784
TI  - One-pot synthesis of functionalized 4,5-dihydroisoxazole derivatives via nitrile
      oxides and biological evaluation with plant cells.
AB  - 1,3 Dipolar cycloadditions of nitrile oxides generated in situ in the presence of
      a variety of olefins provided 4,5-dihydroisoxazoles. The whole procedure could be
      performed in a practical and efficient one-pot operation. The products are of
      excellent purity (95%) and are isolated in 60-83% yields. Some of them enhanced
      the accumulation of indole alkaloids in periwinkle cell cultures.

PMID- 14697785
TI  - 2,6-Bis(3,4,5-trihydroxybenzylydene) derivatives of cyclohexanone: novel potent
      HIV-1 integrase inhibitors that prevent HIV-1 multiplication in cell-based
      assays.
AB  - A number of 2,6-bisbenzylidenecyclohexane-1-one derivatives have been synthesized
      and tested as HIV-1 integrase (IN) inhibitors with the aim of obtaining compounds
      capable to elicit antiviral activity at non-cytotoxic concentrations in cell
      based assays. 3,5-Bis(3,4,5-trihydroxybenzylidene)-4-oxocyclohexaneacetic acid
      (20d) resulted one of the most potent and selective derivatives in acutely
      infected MT-4 cells (EC(50) and CC(50) values of 2 and 40 microM, respectively).
      In enzyme assays with recombinant HIV-1 integrase (rIN), this compound proved
      able to inhibit both 3'-processing and disintegration with IC(50) values of 0.2
      and 0.5 microM, respectively. In order to develop a model capable to predict the
      anti HIV-IN activity and useful to design novel derivatives, we performed a
      comparative molecular field analysis (CoMFA) like 3-D-QSAR. In our model the
      ligands were described quantitatively in the GRID program, and the model was
      optimized by selecting only the most informative variables in the GOLPE program.
      We found the predictive ability of the model to increase significantly when the
      number of variables was reduced from 20,925 to 1327. A Q(2) of 0.73 was obtained
      with the final model, confirming the predictive ability of the model. By studying
      the PLS coefficients in informative 3-D contour plots, ideas for the synthesis of
      new compounds could be generated.

PMID- 14697786
TI  - Effect of abietane diterpenes from Plectranthus grandidentatus on T- and B
      lymphocyte proliferation.
AB  - Five known abietane diterpenes of the royleanone and coleon type, namely, fatty
      acid esters of 7alpha-acyloxy-6beta-hydroxyroyleanone (1), grandidone A (2),
      7alpha-acetoxy-6beta-hydroxyroyleanone (3), 6beta,7alpha-dihydroxyroyleanone (4)
      and coleon U (5), isolated from Plectranthus grandidentatus, were evaluated for
      their effect on the proliferation of human lymphocytes induced by the mitogen
      PHA. All except 4, showed a dose-dependent suppressor effect, with 3 yielding the
      most potent antiproliferative activity, followed by 5. These two compounds, that
      represent diterpenes of the royleanone and coleon type respectively, were also
      shown to be potent inhibitors of mouse splenocyte proliferation induced by ConA
      or LPS mitogens. However, the sensitivity of ConA-stimulated splenocytes to their
      suppressive effect was higher, suggesting a preferential inhibition of T
      lymphocyte proliferation. The antiproliferative activity of 3 seemed to be
      exerted without affecting the expression of the lymphocyte activation marker
      CD69. On the contrary, 5 was shown to reduce the expression of CD69 of TCD8(+)
      and B-cells, suggesting a relationship between its antiproliferative effect and
      the expression of this early marker of activation on these cell populations. The
      capacity of 5 to induce apoptosis on ConA-stimulated splenocytes could also be
      related with its antiproliferative activity.

PMID- 14697787
TI  - Syntheses of tetrahydroxyazepanes from chiro-inositols and their evaluation as
      glycosidase inhibitors.
AB  - Two pairs of C(2)-symmetric tetrahydroxyazepanes [(-), (+)-1 and (-), (+)-2] have
      been synthesized from the enantiomeric chiro-inositols and evaluated as
      glycosidase inhibitors. Alternative syntheses of ido-tetrahydroxyazepanes (-)-
      and (+)-2 from myo-inositol were also developed. The key synthetic
      transformations were glycol fission and cyclization of the derived dialdehydes by
      double reductive amination. The D-manno-tetrahydroxyazepane [(-)-1] showed
      selective inhibition of alpha-L-fucosidase and beta-D-galactosidase, while the
      enantiomer [(+)-1] was a selective inhibitor of an alpha-D-galactosidase. In
      contrast, the L-ido-tetrahydroxyazepane (+)-2 was a broad spectrum hexosidase
      inhibitor, but showed none of the reported hexosaminidase inhibition. Its
      enantiomer (-)-2 is a poor hexosidase inhibitor.

PMID- 14697788
TI  - A novel and facile preparation of bremazocine enantiomers through optically pure
      N-norbremazocines.
AB  - In order to provide ready access to multigram quantities of the optically pure
      bremazocines [(-)- and (+)-9,9-dimethyl-5-ethyl-2-hydroxy-2-(1-hydroxy
      cyclopropylmethyl)-6,7-benzomorphan)], we have developed an improved non
      chromatographic synthesis, and determined the optical purity of their N-nor
      precursors using a rapid and relatively simple 1H NMR method based on
      diastereomeric derivatization with optically pure 1-phenylethylisocyanate. This
      method of determining optical purity should be readily amenable to similar
      systems containing phenolic amino functionalities. Finally, a greatly simplified
      methodology for introduction of the N-(1-hydroxycyclopropylmethyl) substituent in
      bremazocine is described. The improved synthetic method-the overall yield was
      increased about 3-fold-combined with the practical methodology to determine
      optical purity will considerably facilitate the employment of these enantiomers
      as pharmacological tools for examination of the kappa-opioid receptor system, as
      well as their evaluation as drug abuse treatment agents. This synthesis will also
      enable the study of these enantiomers for other, non-classical applications
      (e.g., treatment agents for HIV).

PMID- 14697789
TI  - 8-Quinolinamines conjugated with amino acids are exhibiting potent blood
      schizontocidal antimalarial activities.
AB  - Alanine, lysine, ornithine and valine conjugated to primaquine and other 8
      quinolinamine antimalarials were prepared for blood-schizontocidal antimalarial
      activity evaluation. The analogues were examined in vivo against Plasmodium
      berghei (drug-sensitive strain) and Plasmodium yoelii nigeriensis (highly
      virulent multi-drug-resistant strain) infected mice models. N(1)-[4-(5-Butoxy-4
      ethyl-6-methoxy-8-quinolylamino)pentyl]-(2S)-2,6-diaminohexanamide (20) which
      showed curative activity at 5mg/kg in the P. berghei test emerged as the most
      effective compound. N(1)-[4-(4-Ethyl-5-hexoxy-6-methoxy-8-quinolylamino)pentyl]
      (2S)-2,6-diaminohexanamide (22) exhibited curative activity at 50mg/kg against P.
      yoelii nigeriensis in mice and emerged as the most potent analogue against multi
      drug resistant strain. The results of this study represent development of highly
      potent 8-quinolinamines for antimalarial drug development.

PMID- 14697790
TI  - Relationship between structure and permeability of dipeptide derivatives
      containing tryptophan and related compounds across human intestinal epithelial
      (Caco-2) cells.
AB  - The permeability of dipeptide derivatives containing tryptophans and indole
      derivatives through Caco-2 cells was used as an in vitro intestinal absorption
      model in order to clarify structural factors which influence their intestinal
      epithelial permeation and metabolism. Most peptide derivatives were hydrolysed
      not only by the cytosolic enzymes in Caco-2 cells during permeation but also by
      enzymes released to the apical solution before cell permeation. The N-terminal
      blocked dipeptides were more resistant to hydrolases expressed in the Caco-2
      cells and indole derivatives were not entirely degraded. Based on compound
      concentration dependency and comparison of permeability coefficients in apical-to
      basolateral and basolateral-to-apical directions, the main absorption mechanism
      of compounds were determined. Compounds were then classified into three groups;
      (1) passively transported compounds, (2) actively transported compounds and (3)
      compounds excreted by P-glycoprotein.

PMID- 14697791
TI  - Relationships between structure and high-throughput screening permeability of
      peptide derivatives and related compounds with artificial membranes: application
      to prediction of Caco-2 cell permeability.
AB  - To evaluate absorption of compounds across the membrane via a transcellular
      route, the permeability of peptide derivatives and related compounds was measured
      by the parallel artificial membrane permeation assay (PAMPA). The permeability
      coefficients by PAMPA were analyzed quantitatively using classical QSAR and
      Volsurf approaches with the physicochemical parameters. The results from both
      approaches showed that hydrogen bonding ability of molecules in addition to
      hydrophobicity at a particular pH were significant in determining variations in
      PAMPA permeability coefficients. The relationship between Caco-2 cell
      permeability and artificial lipid membrane permeability was then determined. The
      compounds were sorted according to their absorption pathway in the plot of the
      Caco-2 cell and PAMPA permeability coefficients.

PMID- 14697792
TI  - Synthesis and pharmacological assessment of derivatives of isoxazolo[4,5
      d]pyrimidine.
AB  - A series of new 5-alkyl and 5-arylisoxazolo[4,5-d]pyrimidinones (5a-g, 6-8) were
      prepared from 4-amino-3-oxo-isoxazolidine-5-carboxylic acid amide. Some of the
      aryl derivatives of isoxazolo[4,5-d]pyrimidine were tested pharmacologically in
      comparison with Diazepam. Compounds 5b-d and 7 demonstrated interesting
      anxiolytic activity.

PMID- 14697793
TI  - Synthesis of 4-methyl-thio-phenyl-propylamine and the evaluation of its
      interaction with different amine oxidases.
AB  - A new molecule, the 4-methyl-thio-phenyl-propylamine (PrNH(2)) was synthesized
      and its biological interaction with different amine oxidases such as
      semicarbazide sensitive amine oxidase (SSAO) [E.C.1.4.3.6], and monoamine oxidase
      [E.C.1.4.3.4] under its two isoforms, MAO A and MAO B, has been assessed. The
      substrate specifities of MAO and SSAO overlap to some extent. In this context,
      the search of new molecules, able to discriminate between these different amine
      oxidases is very important as it will allow greater elucidation of the SSAO's
      role in physiological and pathological conditions. We report for the first time,
      the synthesis and evaluation of a new molecule which has a high affinity towards
      the SSAO family of enzymes, more so than previously described and furthermore an
      ability to discriminate between the different amine oxidases.

PMID- 14697794
TI  - Structure-activity and structure-metabolism relationships of HIV protease
      inhibitors containing the 3-hydroxy-2-methylbenzoyl-allophenylnorstatine
      structure.
AB  - A series of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors
      containing substituted all-phenylnorstatine [APNS: (2S,3S)-3-amino-2-hydroxy-4
      phenylbutyric acid] were designed and synthesized. From the structure-metabolism
      relationship of this type of HIV protease inhibitors, the compounds having para
      substitution of the phenyl ring of Apns and/or 2,6-disubstitution of the P2'
      benzylamine were found to be able to avoid the P2 phenol glucuronidation that
      occurs with SM-319777 (formerly named JE-2147, KNI-764); one of the main
      metabolic pathways of SM-319777. These new analogues, such as SM-322377, had more
      desirable pharmacokinetic profiles and more potent antiviral activity against not
      only wild type HIV-1 but also the multi-drug-resistant HIV-1 than SM-319777.

PMID- 14697795
TI  - Saturation-transfer difference NMR studies for the epitope mapping of a
      carbohydrate-mimetic peptide recognized by an anti-carbohydrate antibody.
AB  - Saturation-transfer difference NMR spectroscopy (STD-NMR) experiments have been
      performed to analyze the topography or epitope of the octapeptide MDWNMHAA
      recognized by the anti-carbohydrate antibody SYA/J6 in solution; the antibody is
      directed against the Shigella flexneri Y O-antigen polysaccharide. The results
      permit a valuable comparison of solution versus crystal-structure data, and
      provide insight for the design of the next-generation binding ligands.

PMID- 14697796
TI  - Mexico, 2004: research for global health and security.

PMID- 14697797
TI  - Inequality and road-traffic injuries: call for action.

PMID- 14697798
TI  - Antimalarial activity of artemisinins: identification of a novel target?

PMID- 14697799
TI  - Innovation and placebos in research: a new design of clinical trial.

PMID- 14697800
TI  - A riddle wrapped in a mystery inside an enigma: Brainerd diarrhoea turns 20.

PMID- 14697802
TI  - Frequency of venous thromboembolism in low to moderate risk long distance air
      travellers: the New Zealand Air Traveller's Thrombosis (NZATT) study.
AB  - BACKGROUND: The frequency and role of risk factors for venous thromboembolism
      related to air travel is uncertain. We aimed to establish the frequency of this
      disorder in a group of long distance air travellers and to investigate the role
      of potential risk factors. METHODS: We designed a prospective study into which we
      recruited individuals aged between 18 and 70 years, travelling for 4 h or more by
      aircraft. D-dimer measurement was done before and after travel. Participants with
      a negative D-dimer (<500 ng/L) before travel were included in the study. Those
      who became D-dimer positive or developed high clinical probability symptoms
      during the 3 months after travel were investigated with bilateral compression
      ultrasonography and CT pulmonary angiography. Suspected clinical and
      thrombophilic risk factors, and use of prophylactic measures, were assessed.
      FINDINGS: 1000 individuals were recruited, with 878 meeting inclusion criteria
      and completing the study. All participants travelled at least 10 h, with a mean
      total duration of air travel of 39 h (SD 12.5). 112 patients underwent
      radiological assessment on return. Frequency of venous thromboembolism associated
      with travel was 1.0% (9/878, 95% CI 0.5-1.9), which included four cases of
      pulmonary embolism and five of deep venous thrombosis. Six patients with venous
      thromboembolism had pre-existing clinical risk factors, two had a recognised
      thrombophilic risk factor, two travelled exclusively in business class, five used
      aspirin, and four wore compression stockings. INTERPRETATION: Our results suggest
      an association between multiple long distance air flights and venous
      thromboembolism, even in individuals at low to moderate risk. The role of
      traditional risk factors and prophylactic measures in air travel-related venous
      thromboembolism needs further investigation.

PMID- 14697803
TI  - Long-term effects of protease-inhibitor-based combination therapy on CD4 T-cell
      recovery in HIV-1-infected children and adolescents.
AB  - BACKGROUND: There is limited evidence about longer-term effects of combination
      antiretroviral therapy that includes protease inhibitors (PIs) on the
      immunological status of HIV-1-infected children. Better understanding might help
      to resolve questions on when to initiate treatment. METHODS: The change in
      percentage of CD4-positive T lymphocytes (CD4%) was investigated in 1012
      previously treated HIV-1-infected children (aged 0-17 years) who were enrolled in
      research clinics in the USA before 1996 and followed up to 2000. 702 started PI
      based combination therapy. Data analyses ignored subsequent treatment changes.
      FINDINGS: Among the 1012 children, the median CD4% increased from 22% to 28%
      between 1996, when PIs were first prescribed, and 2000. For the 702 who started
      PI-based therapy, the mean CD4% increase after 3 years was largest among
      participants with the greatest immunosuppression (15.7%, 10.6%, 5.1%, and 2.0%
      for participants with CD4% before therapy of <5%, 5-14%, 15-24%, and >25%;
      p<0.0001). After adjustment for pre-PI CD4%, the mean increase was largest among
      the youngest participants (9.2%, 8.0%, and 4.3% for ages <5 years, 5-9 years, and
      >10 years; p=0.001). However, only a minority of significantly immunocompromised
      participants (33%, 26%, and 49% of those with pre-PI CD4% of <5%, 5-14%, or 15
      24%) achieved CD4% values above 25%, whereas 84% of those with pre-PI values
      above 25% maintained such values. INTERPRETATION: Although PI-based therapy was
      associated with substantial improvements in CD4%, initiation before severe
      immunosuppression and at younger ages may be more effective for recovery or
      maintenance of normal CD4%. Randomised investigation of when to start combination
      therapy in children, particularly infants, is needed.

PMID- 14697804
TI  - Effects of subclinical infection on plasma retinol concentrations and assessment
      of prevalence of vitamin A deficiency: meta-analysis.
AB  - BACKGROUND: Vitamin A deficiency adversely affects child morbidity and survival.
      This deficiency is estimated by measurement of plasma retinol concentrations, but
      because plasma retinol is reduced by clinical and subclinical infection, this
      proxy measure can lead to overestimation. Infection and trauma are accompanied by
      rises in concentrations of acute-phase proteins in plasma. We aimed to estimate
      vitamin A deficiency more accurately by measuring changes in plasma retinol and
      acute-phase proteins associated with subclinical infection or convalescence.
      METHODS: We analysed data for concentrations of plasma retinol and one or more
      acute-phase proteins (alpha1-acid-glycoprotein, alpha1-antichymotrypsin, C
      reactive protein, or serum amyloid A) from 15 studies of apparently healthy
      individuals. We generated summary estimates of differences in retinol
      concentrations for incubation, early, and late convalescent phases of infection
      between people with none and those with one or more raised acute-phase proteins.
      We compared these groups in two, three, and four group analyses. We also compared
      a subgroup of apparently healthy preschool (1-5 years) children with results from
      all other studies. FINDINGS: For all four proteins, retinol values were much
      higher in people with normal concentrations of protein, than in individuals with
      raised concentrations (16% higher for alpha1-antichymotrypsin, 18% for alpha1
      acid-glycoprotein, 25% for C-reactive protein, and 32% for serum amyloid A).
      Estimates of the reduction in plasma retinol for individuals with infection
      compared with healthy individuals, were 13% (incubation), 24% (early
      convalescent), and 11% (late convalescent). Estimates of vitamin A deficiency in
      individuals with no raised acute-phase proteins (healthy group) were much the
      same as those obtained by adjustment of plasma retinol concentrations in the
      whole group using acute-phase proteins. INTERPRETATION: We recommend that surveys
      to estimate vitamin A deficiency should include measurements of serum C-reactive
      protein and alpha1-acid-glycoprotein concentrations. Information about acute
      phase proteins will enable plasma retinol concentrations to be corrected where
      sub-clinical infection exists, and the healthy sub-group to be identified.

PMID- 14697805
TI  - Rescue of defective pancreatic secretion in cystic-fibrosis cells by suppression
      of a novel isoform of phospholipase C.
AB  - BACKGROUND: Cystic fibrosis is caused by mutations in the gene encoding an ion
      transport protein, the cystic-fibrosis transmembrane conductance regulator
      (CFTR). Defective secretion of anions is the primary cause of many of the
      clinical manifestations of cystic fibrosis, including pancreatic insufficiency.
      We aimed to identify a molecular mechanism from which a new method to circumvent
      defective pancreatic secretion could be derived. METHODS: Multiple-human-tissue
      RT-PCR and semiquantitative RT-PCR analyses were used to examine gene expression.
      An antisense technique was used in conjunction with radioimmunoassay, Fura-2
      spectrofluorometry, immunohistochemistry, and the short-circuit current technique
      (Ussing chamber) for elucidation of gene function and its application in rescuing
      defective pancreatic secretion. FINDINGS: We cloned a newly identified gene, NYD
      SP27, which has structural similarity to an isoform of phospholipase C. NYD-SP27
      was expressed endogenously in human pancreatic-duct cells and upregulated in
      cystic fibrosis. Suppression of NYD-SP27, by transfection of its antisense into
      human cystic-fibrosis pancreatic-duct cells, resulted in augmentation of
      phospholipase-C-coupled calcium-ion release and protein kinase C activity,
      improvement in the amount of mutated CFTR reaching the plasma membrane, and
      restoration of cAMP-activated pancreatic anion secretion. INTERPRETATION: NYD
      SP27 exerts an inhibitory effect on phospholipase-C-coupled processes that depend
      on calcium ions and protein kinase C, including CFTR trafficking and function.
      Its upregulation in pancreatic-duct cells may reveal a previously unsuspected
      defect in cystic fibrosis contributing to pancreatic insufficiency, and thus
      represents a new target for pharmacological intervention in cystic fibrosis.

PMID- 14697806
TI  - Intracranial haemopoiesis.

PMID- 14697807
TI  - An explosive case.

PMID- 14697808
TI  - Whole blood versus plasma spots for measurement of HIV-1 viral load in HIV
      infected African patients.
AB  - The increasing availability of antiretroviral drugs to HIV-infected populations
      in developing countries highlights the need to develop field-friendly practical
      methods for HIV-1 viral load measurements to monitor the effects of treatment. We
      compared use of whole-blood spots versus plasma dried on filter paper to quantify
      HIV-1 viral load in 51 African patients with HIV-1. The mean log10 HIV-1 viral
      loads were 4.22 for dried plasma spots (DPS) and 4.20 for dried whole-blood spots
      (DBS). The difference between the pairs of log10 viral load for DPS and DBS were
      significantly correlated with their mean (Spearman's r=0.31, p=0.03). This
      correlation between the difference and mean of viral load was no longer evident
      for values of log10 DPS that were less than 5 (r=0.01, p=0.93). For the 38 paired
      values with log10DPS of less than 5, the mean difference (log10DPS-log10DBS) was 
      0.04 (SD 0.29). Dried whole blood stored on filter paper at room temperature
      shows potential as a field-friendly alternative to plasma for measurement of HIV
      1 viral load.

PMID- 14697809
TI  - Steroid-free liver transplantation in children.
AB  - Although corticosteroids have been part of immunosuppressive regimens since the
      early days of transplantation, steroid avoidance could be beneficial. To test
      this hypothesis in paediatric liver transplantation, we compared liver
      transplantation under steroid-free immunosuppression in 20 children, who received
      combined tacrolimus and basiliximab, with that under tacrolimus and steroids in
      20 matched historical recipients as a historical control group. 12-month
      rejection-free survival was 75% in the tacrolimus-basiliximab group compared with
      50% in the steroid group (p=0.05). Growth in the first year after transplantation
      was significantly better in the tacrolimus-basiliximab group than in the steroid
      group. Steroid avoidance was, therefore, not harmful to our patients, and
      combining tacrolimus with basiliximab as a steroid substitution seems a safe
      alternative to tacrolimus and steroid immunosuppression.

PMID- 14697810
TI  - Ask the elephant.

PMID- 14697811
TI  - TB and you and me...personal reflections.

PMID- 14697812
TI  - Global health improvement and WHO: shaping the future.
AB  - A world torn by gross health inequalities is in serious trouble. The global
      health community can do much to reduce suffering and death among vulnerable
      groups. WHO is changing its way of working, alongside member states and financial
      and technical partners, to reach key national health goals and strengthen equity.
      The most urgent objectives include the health-related Millennium Development
      Goals, the 3 by 5 target in HIV/AIDS treatment (to provide 3 million people in
      developing regions with access to antiretroviral treatment by the end of 2005),
      and addressing the growing epidemics of non-communicable diseases. The key to
      achieving these objectives is strengthening of health systems guided by the
      values of Health For All.

PMID- 14697813
TI  - Viral hepatitis B.
AB  - More than 400 million people worldwide are chronically infected by the hepatitis
      B virus. The virus is responsible for more than 300000 cases of liver cancer
      every year and for similar numbers of gastrointestinal haemorrhage and ascites.
      Major breakthroughs have been achieved in diagnosis and treatment of this virus.
      Hepatitis B vaccine reduces incidence of liver cancer. As with hepatitis C,
      advances have been made in molecular virology, especially for naturally occurring
      and treatment-induced mutant viruses. The clinical significance of low viral load
      and genotypes are also under investigation. Currently available monotherapies
      interferon, lamivudine, and adefovir dipivoxil-very rarely eradicate the virus,
      but greatly reduce its replication, necroinflammatory histological activity, and
      progression of fibrosis. Lamivudine, and presumably other nucleoside analogues,
      can reverse cirrhosis of the liver.

PMID- 14697814
TI  - Viral hepatitis C.
AB  - More than 170 million people worldwide are chronically infected with the
      hepatitis C virus (HCV), which is responsible for more than 100000 cases of liver
      cancer per year, with similar numbers of digestive haemorrhage and ascites
      episodes. Major breakthroughs have been made in diagnosis and treatment, and
      advances in molecular biology mean that the replicative state of the virus can
      now be assessed. Genotype and serum viral load are useful predictors of response
      to treatment. The combination of pegylated interferon and ribavirin can eradicate
      the virus in more than 50% of patients. These antiviral treatments reduce liver
      fibrosis progression and can reverse cirrhosis. Unfortunately, even in developed
      countries, death due to hepatitis C is increasing because of inadequate detection
      and treatment.

PMID- 14697815
TI  - Read all about it: The Lancet's Paper of the Year, 2003.

PMID- 14697816
TI  - Benjamin Jesty: new light in the dawn of vaccination.

PMID- 14697817
TI  - Remember to look below.

PMID- 14697818
TI  - Virtual dissection: a lesson from the 18th century.

PMID- 14697819
TI  - William Blake's Milton, John Birch's "Electrical Magic", and the "falling star".

PMID- 14697820
TI  - Selective decontamination of digestive tract in intensive care.

PMID- 14697821
TI  - Post-conference thoughts from Malawi.

PMID- 14697822
TI  - Selective decontamination of digestive tract in intensive care.

PMID- 14697823
TI  - Selective decontamination of digestive tract in intensive care.

PMID- 14697824
TI  - Selective decontamination of digestive tract in intensive care.

PMID- 14697825
TI  - Selective decontamination of digestive tract in intensive care.

PMID- 14697827
TI  - Paulesco: science and political views.

PMID- 14697828
TI  - Contract for UK consultants.

PMID- 14697829
TI  - The selection of doctors.

PMID- 14697830
TI  - Primary prevention of stroke.

PMID- 14697831
TI  - Effect of Estonian law on prospects for public health research.

PMID- 14697832
TI  - A bad dose of the 'flu.

PMID- 14697835
TI  - Rest In Peace, without comment.

PMID- 14697844
TI  - Frank Buckland (1826-80).

PMID- 14697845
TI  - Confused about Christmas.

PMID- 14697848
TI  - Special issue: animal models for tissue engineering applications.

PMID- 14697849
TI  - Bone tissue engineering and spinal fusion: the potential of hybrid constructs by
      combining osteoprogenitor cells and scaffolds.
AB  - In this paper, we discuss the current knowledge and achievements on bone tissue
      engineering with regard to spinal fusion and highlight the technique that employs
      hybrid constructs of porous scaffolds with bone marrow stromal cells. These
      hybrid constructs potentially function in a way comparable to the present golden
      standard, the autologous bone graft, which comprises besides many other factors,
      a construct of an optimal biological scaffold with osteoprogenitor cells.
      However, little is known about the role of the cells in autologous grafts, and
      especially survival of these cells is questionable. Therefore, more research will
      be needed to establish a level of functioning of hybrid constructs to equal the
      autologous bone graft. Spinal fusion models are relevant because of the
      increasing demand for graft material related to this procedure. Furthermore, they
      offer a very challenging environment to further investigate the technique.
      Anterior and posterolateral animal models of spinal fusion are discussed together
      with recommendations on design and assessment of outcome parameters.

PMID- 14697850
TI  - Spinal fusion surgery: animal models for tissue-engineered bone constructs.
AB  - Animal models have been used extensively to investigate the biology of fracture
      healing and spinal fusion. The goal of each spinal fusion model is to try and
      reproduce the correct sequence of events during osseous healing in humans. Animal
      models allow us the capability of dialing in fusion rates and fusion parameters
      depending upon the study conditions. These models have become invaluable in
      assessing the clinical potential of emerging technologies such as recombinant
      growth factors and gene therapy.

PMID- 14697851
TI  - Skeletal tissue engineering-from in vitro studies to large animal models.
AB  - Bone is a tissue with a strong regenerative potential. New strategies for tissue
      engineering of bone should therefore only focus on defects with a certain size
      that will not heal spontaneously. In the development of tissue-engineered
      constructs many variables may play a role, e.g. the source of the cells used, the
      design and mechanical properties of the scaffold and the concentration and mode
      of application of growth factor(s). Models for studying new strategies for tissue
      engineering of bone should be based on the target tissue to be restored. However,
      in light of the many potential variables, which may also interact if used in
      combination(s), there is also a large need for relatively simple models in which
      variables can be tested in a limited number of animals. Moreover, in compromised
      bone there may be a problem with the load-bearing capacity of the remaining
      healthy bone. In this light, an important prerequisite for tissue-engineering
      constructs is that they can be tested in loaded conditions. Particularly, this
      latter prerequisite is very difficult to achieve. Therefore, in vitro tests for
      mechanical stability are very useful for evaluating the mechanical consequences
      of a particular reconstruction procedure prior to the animal experiment. Before a
      tissue-engineered construct can be introduced into a clinical trial, a final test
      should be available in a large animal model that is as close and relevant to a
      particular problematic clinical situation as possible.In the past, a series of
      models were developed in our laboratory that are very useful for testing tissue
      engineered constructs. In this paper, we focus on the use of relatively new
      simple in vitro and in vivo models for hip revision surgery, segmental bone
      defect restoration and tumour surgery.

PMID- 14697852
TI  - Role of gene therapy in tissue engineering procedures in rheumatology: the use of
      animal models.
AB  - Tissue engineering is not only the application of cells and scaffolds to generate
      a new tissue but should also bring into play biological principles to guide
      cellular behavior. A way to modify cellular behavior is genetic modification of
      the cells used for tissue engineering (gene therapy). In the field of rheumatic
      diseases, cellular modification by overexpressing anabolic factors, such as
      insulin-like growth factor-I or transforming growth factor beta, or inhibitors of
      catabolic cytokines or proteolytic enzymes can protect tissues form further
      destruction and stimulate tissue repair. To test the effect of transgenes on
      tissue engineering adequate test systems have to be available. Initial testing
      can be done in simple in vitro systems. However, animal models are unavoidable to
      study the interaction between the environment and tissue engineering. Optimal
      models to study gene therapy in combination with tissue engineering in the field
      of rheumatology are not available at this moment. Arthritis models are mainly
      developed in small animals while high-quality tissue engineering experiments ask
      for a large animal model. Development of animal models that can be used for
      tissue engineering experiments and mimic end stage arthritic diseases is needed.

PMID- 14697853
TI  - Animal models of spinal cord injury for evaluation of tissue engineering
      treatment strategies.
AB  - Tissue engineering approaches to spinal cord injury (SCI) treatment are
      attractive because they allow for manipulation of native regeneration processes
      involved in restoration of the integrity and function of damaged tissue. A
      clinically relevant spinal cord regeneration animal model requires that the model
      mimics specific pathologic processes that occur in human SCI. This manuscript
      discusses issues related to preclinical testing of tissue engineering spinal cord
      regeneration strategies from a number of perspectives. This discussion includes
      diverse causes, pathology and functional consequences of human SCI, general and
      species related considerations, technical and animal care considerations, and
      data analysis methods.

PMID- 14697854
TI  - Animal models for cartilage reconstruction.
AB  - Animal models are widely used to develop and evaluate tissue-engineering
      techniques for the reconstruction of damaged human articular cartilage. For the
      purpose of this review, these model systems will include in vitro culture of
      animal cells and explants, heterotopic models of chondrogenesis, and articular
      cartilage defect models. The objectives for these preclinical studies are to
      engineer articular cartilage for the functional restoration of a joint surface
      that appears anatomically, histologically, biologically, biochemically, and
      mechanically to resemble the original joint surface. While no animal model
      permits direct application to humans, each is capable of yielding principles on
      which decisions can be made that might eventually translate into a human
      application. Clearly, the use of animal models has and will continue to play a
      significant role in the advancement of this field. Each animal model has specific
      advantages and disadvantages. The key issue in the selection of an appropriate
      animal model is to match the model to the question being investigated and the
      hypothesis to be tested. The purpose of this review is to discuss issues
      regarding animal model selection, the benefits and limitations of these model
      systems, scaffold selection with emphasis on polymers, and evaluation of the
      tissue-engineered articular cartilage.

PMID- 14697855
TI  - Tissue engineering of the meniscus.
AB  - Meniscus lesions are among the most frequent injuries in orthopaedic practice and
      they will inevitably lead to degeneration of the knee articular cartilage. The
      fibro-cartilage-like tissue of the meniscus is notorious for its limited
      regenerative capacity. Tissue engineering could offer new treatment modalities
      for repair of meniscus tears and eventually will enable the replacement of a
      whole meniscus by a tissue-engineered construct. Many questions remain to be
      answered before the final goal, a tissue-engineered meniscus is available for
      clinical implementation. These questions are related to the selection of an
      optimal cell type, the source of the cells, the need to use growth factor(s) and
      the type of scaffold that can be used for stimulation of differentiation of cells
      into tissues with optimal phenotypes. Particularly in a loaded, highly complex
      environment of the knee, optimal mechanical properties of such a scaffold seem to
      be of utmost importance. With respect to cells, autologous meniscus cells seems
      the optimal cell source for tissue engineering of meniscus tissue, but their
      availability is limited. Therefore research should be stimulated to investigate
      the suitability of other cell sources for the creation of meniscus tissue. Bone
      marrow stroma cells could be useful since it is well known that they can
      differentiate into bone and cartilage cells. With respect to growth factors, TGF
      beta could be a suitable growth factor to stimulate cells into a fibroblastic
      phenotype but the problems of TGF-beta introduced into a joint environment should
      then be solved. Polyurethane scaffolds with optimal mechanical properties and
      with optimal interconnective macro-porosity have been shown to facilitate
      ingrowth and differentiation of tissue into fibro-cartilage. However, even these
      materials cannot prevent cartilage degeneration in animal models. Surface
      modification and/or seeding of cells into the scaffolds before implantation may
      offer a solution for this problem in the future.This review focuses on a number
      of specific questions; what is the status of the development of procedures for
      lesion healing and how far are we from replacing the entire meniscus by a (tissue
      engineered) prosthesis. Subquestions related to the type of scaffold used are: is
      the degree of tissue ingrowth and differentiation related to the initial
      mechanical properties and if so, what is the influence of those properties on the
      subsequent remodelling of the tissue into fibro-cartilage; what is the ideal pore
      geometry and what is the optimal degradation period to allow biological
      remodelling of the tissue in the scaffold. Finally, we will finish with our
      latest results of the effect of tear reconstruction and the insertion of
      prostheses on articular cartilage degradation.

PMID- 14697856
TI  - Animal models for tracheal research.
AB  - Tracheal research covers two main areas of interest: tracheal reconstruction and
      tracheal fixation. Tracheal reconstructions are aimed at rearranging or replacing
      parts of the tracheal tissue using implantation and transplantation techniques.
      The indications for tracheal reconstruction are numerous: obstructing tracheal
      tumors, trauma, post-intubation tissue reactions, etc. Although in the past years
      much progress has been made, none of the new developed techniques have resulted
      in clinical application at large scale. Tissue engineering is believed to be the
      technique to provide a solution for reconstruction of tracheal defects. Although
      developing functional tracheal tissue from different cultured cell types is still
      a challenge. Tracheal fixation research is relatively new in the field and
      concentrates on solving fixation-related problems for laryngectomized patients.
      In prosthetic voice rehabilitation tracheo-esophageal silicon rubber speech
      valves and tracheostoma valves are used. This is often accompanied by many
      complications. The animal models used for tracheal research vary widely and in
      most publications proper scientific arguments for animal selection are never
      mentioned. It showed that the choice on animal models is a multi-factorial
      process in which non-scientific arguments tend to play a key role. The aim of
      this study is to provide biomaterials scientists with information about tracheal
      research and the animal models used.

PMID- 14697857
TI  - Tissue engineering auricular reconstruction: in vitro and in vivo studies.
AB  - Although investigators have demonstrated that neocartilage can be constituted in
      a predetermined shape and in complex three-dimensional structures, such as a
      human ear, by using cell transplantation on polymer constructs, many unsolved
      problems still remain. The crucial issues for auricular tissue engineering
      consisted of optimal cell culture environment, choice of polymers, behavior of
      chondrocytes, study of cell-polymer constructs in an acceptable animal model, and
      long-term structural integrity. Here we describe our tissue engineering
      approaches for auricular reconstruction including auricular scaffold fabrication,
      in vitro chondrogenesis, in vivo immunocompromized xenograft and immunocompetent
      autologous animal models, and long-term follow-up. Though many current obstacles
      regarding auricular tissue engineering still exist, we demonstrate techniques of
      auricular scaffold fabrication with promising in vitro and in vivo neocartilage
      formation, optimal selection and application of animal models, and, to the best
      of our knowledge, the first report of different biodegradable biomaterial trials
      and the longest in vivo results (10 months) for auricular tissue engineering.

PMID- 14697858
TI  - Porcine wound models for skin substitution and burn treatment.
AB  - Skin regeneration is an important field of tissue engineering. Especially in
      larger burns and chronic wounds, present treatments are insufficient in
      preventing scar formation and promoting healing. Initial screening of potentially
      interesting products for skin substitution is usually done by in vitro tests.
      Before entering the clinic, however, in vivo studies in immunocompetent animals
      are necessary to prove efficacy and provide information on safety aspects. We
      have obtained extensive experience using the domestic pig as test animal for
      studies on skin replacement materials, including tissue engineered skin
      substitutes, and burn wound treatment. Two models are described: an excisional
      wound model for testing of dermal and epidermal substitutes and a burn wound
      model for contact and scald burns, which allows testing of modern wound dressings
      in comparison to the present gold standards in burn treatment. The results of
      these experiments show that in vivo testing was able to reveal (dis)advantages of
      the treatments which were not detected during in vitro studies.

PMID- 14697859
TI  - Freeze-dried poly(D,L-lactic acid) macroporous guidance scaffolds impregnated
      with brain-derived neurotrophic factor in the transected adult rat thoracic
      spinal cord.
AB  - The effects of poly(D,L-lactic acid) macroporous guidance scaffolds (foams) with
      or without brain-derived neurotrophic factor (BDNF) on tissue sparing, neuronal
      survival, axonal regeneration, and behavioral improvements of the hindlimbs
      following implantation in the transected adult rat thoracic spinal cord were
      studied. The foams were embedded in fibrin glue containing acidic-fibroblast
      growth factor. One group of animals received fibrin glue with acidic-fibroblast
      growth factor only. The foams were prepared by a thermally induced polymer
      solvent phase separation process and contained longitudinally oriented macropores
      connected to each other by a network of micropores. Both foams and fibrin only
      resulted in a similar gliotic and inflammatory response in the cord-implant
      interfaces. With BDNF foam, up to 20% more NeuN-positive cells in the spinal
      nervous tissue close to the rostral but not caudal spinal cord-implant interface
      survived than with control foam or fibrin only at 4 and 8 weeks after
      implantation. Semithin plastic sections and electron microcopy revealed that
      cells and axons more rapidly invaded BDNF foam than control foam. Also, BDNF foam
      contained almost twice as many blood vessels than control foam at 8 weeks after
      implantation. Tissue sparing was similar in all three implantation paradigms;
      approximately 42% of tissue was spared in the rostral cord and approximately 37%
      in the caudal cord at 8 weeks post grafting. The number of myelinated and
      unmyelinated axons was low and not different between the two types of foams. Many
      more axons were found in the fibrin only graft. Serotonergic axons were not found
      in any of the implants and none of the axons regenerated into the caudal spinal
      cord. The behavioral improvements in the hindlimbs were similar in all groups.
      These findings indicated that foam is well tolerated within the injured spinal
      cord and that the addition of BDNF promotes cell survival and angiogenesis.
      However, the overall axonal regeneration response is low. Future research should
      explore the use of poly(D,L-lactic acid) foams, with or without axonal growth
      promoting factors, seeded with Schwann cells to enhance the axonal regeneration
      and myelination response.

PMID- 14697860
TI  - Transection of peripheral nerves, bridging strategies and effect evaluation.
AB  - Disruption of peripheral nerves due to trauma is a frequently occurring clinical
      problem. Gaps in the nerve are bridged by guiding the regenerating nerves along
      autologous grafts or artificial guides. This review gives an overview on the
      different methods of nerve repair techniques. Conventional suturing techniques
      are discussed as well as the use of e.g. biological, synthetic, non-degradable or
      degradable nerve guides. Functional assessment showed that repair of a gap with a
      bio-degradable guide is superior to that with autologous grafts. But still, long
      lasting changes were observed in the Sciatic Function Index (SFI), abnormal
      walking patterns, disturbed Electro Myo Graphic (EMG) patterns, next to shifts in
      the histochemical properties of the muscles and longlasting abnormalities in
      neuromuscular contacts. These phenomena are explained by an at-random
      reinnervation. When transecting the nerve at young ages, this did not lead to
      enhanced recovery. Rearing rats operated at adult age in an enriched environment,
      also had no beneficial effect. Future research should aim at developing longer
      guides, possibly lined with Schwann cells, or additives, improving specific
      reinnervation of the former target areas.

PMID- 14697861
TI  - Selection of biomaterials for peripheral nerve regeneration using data from the
      nerve chamber model.
AB  - Peripheral nerve regeneration has been studied in a variety of animal models. Of
      these, the nerve chamber model has clearly dominated. It has been used to
      generate a large base of data that, however, cannot be analyzed usefully due to
      lack of standardization of experimental conditions and assays. Lack of
      standardization of critical experimental parameters of the model has, however,
      greatly limited the opportunity to compare directly data from independent
      investigators; as a result, progress in understanding conditions for optimal
      nerve regeneration has been stunted. In this article, we provide an overview of
      the major experimental parameters that must be controlled in order to generate
      data from independent investigators that can be compared directly (normalized
      data). Such parameters include the gap length, animal species, and the identity
      of assays used to evaluate the product of the regenerative process. Use of the
      recently introduced concept of critical axon elongation, the gap length at which
      the probability of axonal outgrowth (reinnervation) across the gap is 50%, leads
      to generation of a normalized database that includes data from several
      independent investigators. Conclusions are drawn about the relative efficacy of
      the various biomaterials and devices employed. Nerve chamber configurations that
      had the highest regenerative activity were those in which the tube wall comprised
      collagen and certain synthetic biodegradable polymers rather than silicone, and
      was cell-permeable rather than protein-permeable. In addition, the following tube
      fillings showed very high regenerative activity: suspensions of Schwann cells; a
      solution either of acidic or basic fibroblast growth factor; insoluble ECM
      substrates rather than solutions or gels; polyamide filaments oriented along the
      tube axis; highly porous, insoluble analogs of the ECM with specific structure
      and controlled degradation rate.

PMID- 14697862
TI  - Animal models of liver regeneration.
AB  - Owing to its powers of regeneration, the liver is capable of in vivo "tissue
      engineering" which enables complete restoration of liver architecture and re
      establishment of the specific functions of the liver after various types of liver
      injury. Our current understanding of liver regeneration forms the basis of modern
      liver surgery and is now taken into consideration in the treatment of many liver
      diseases, in liver transplantation and hepatic tissue engineering. These advances
      have been achieved primarily by studies of liver regeneration in animal models
      after partial hepatectomy, attention being focused on the general mechanisms of
      cell proliferation. In recent years, however, toxin-induced models of liver
      regeneration have assumed growing importance, and by studying the interaction
      between cell damage and cell regeneration have made possible an investigation of
      liver regeneration of greater clinical relevance. However, the mechanisms of
      liver regeneration in patients with pre-existing chronic liver damage such as
      liver cirrhosis are still largely unexplored. This review examines and critically
      appraises the various approaches to the study of liver regeneration in animal
      models, including both surgical and pharmacological approaches.

PMID- 14697863
TI  - Large animal models of fulminant hepatic failure in artificial and bioartificial
      liver support research.
AB  - Among the large range of organs involved in the field of tissue engineering
      (skin, blood vessels, cartilage, etc.) the liver has been given broad attention
      in the last decade. Liver support systems encompassing artificial and
      bioartificial systems are applied to treat patients with fulminant hepatic
      failure (FHF) as a bridge to orthotopic liver transplantation or to liver
      regeneration. To test safety, technical applicability and therapeutic effect of
      liver support systems, reliable animal models are needed. Due to the complexity
      of FHF many diverse attempts have been made to develop an adequate animal model
      to study liver failure, liver regeneration and liver support systems. In this
      paper an overview is given of the different models and their advantages and
      disadvantages are discussed. Suggestions are made for the most suitable large
      animal model to test liver support systems.

PMID- 14697864
TI  - The use of animal models in developing the discipline of cardiovascular tissue
      engineering: a review.
AB  - Cardiovascular disease remains one of the major causes of death and disability in
      the Western world. Tissue engineering offers the prospect of being able to meet
      the demand for replacement of heart valves, vessels for coronary and lower limb
      bypass surgery and the generation of cardiac tissue for addition to the diseased
      heart. In order to test prospective tissue-engineered devices, these constructs
      must first be proven in animal models before receiving CE marking or FDA approval
      for a clinical trial. The choice of animal depends on the nature of the tissue
      engineered construct being tested. Factors that need to be considered include
      technical requirements of implanting the construct, availability of the animal,
      cost and ethical considerations. In this paper, we review the history of animal
      studies in cardiovascular tissue engineering and the uses of animal tissue as
      sources for tissue engineering.

PMID- 14697865
TI  - Engineered heart tissue for regeneration of diseased hearts.
AB  - Cardiac tissue engineering aims at providing contractile heart muscle constructs
      for replacement therapy in vivo. At present, most cardiac tissue engineering
      attempts utilize heart cells from embryonic chicken and neonatal rats and
      scaffold materials. Over the past years our group has developed a novel technique
      to engineer collagen/matrigel-based cardiac muscle constructs, which we termed
      engineered heart tissue (EHT). EHT display functional and morphological
      properties of differentiated heart muscle and can be constructed in different
      shape and size from collagen type I, extracellular matrix proteins
      (Matrigel((R))), and heart cells from neonatal rats and embryonic chicken. First
      implantation studies in syngeneic Fischer 344 rats provided evidence of EHT
      survival and integration in vivo. This review will focus on our experience in
      tissue engineering of cardiac muscle. Mainly, EHT construction, matrix
      requirements, potential applications of different cell types including stem
      cells, and our first implantation experiences will be discussed. Despite many
      critical and unresolved questions, we believe that cardiac tissue engineering in
      general has an interesting perspective for the replacement of malfunctioning
      myocardium and reconstruction of congenital malformations.

PMID- 14697866
TI  - A comparative study of three different biomaterials in the engineering of
      skeletal muscle using a rat animal model.
AB  - Defects caused by traumatic or postsurgical loss of muscle mass may result in
      severe impairments of the functionality of skeletal muscle. Tissue engineering
      represents a possible approach to replace the lost or defective muscle. The aim
      of this study was to compare the suitability of three different biomaterials as
      scaffolds for rat myoblasts, using a new animal model. PKH26-fluorescent-stained
      cultured rat myoblasts were either seeded onto polyglycolic acid meshes or,
      alternatively, suspended in alginate or in hyaluronic acid-hydrogels. In each of
      the eight Fisher CDF-344 rats, four capsule pouches were induced by subcutaneous
      implantation of four silicone sheets. After two weeks the silicone sheets were
      removed and myoblast-biomaterial-constructs were implanted in the preformed
      capsules. Specimens were harvested after four weeks and examined histologically
      by H&E-staining and fluorescence microscopy. All capsules were well-vascularized.
      Implanted myoblasts fused by forming multinucleated myotubes. This study
      demonstrates that myoblasts seeded onto different biomaterials can be
      successfully transplanted into preformed highly vascularized capsule pouches. Our
      animal model has paved the way for studies of myoblast-biomaterial
      transplantations into an ectopic non-muscular environment.

PMID- 14697867
TI  - A rabbit model to tissue engineer the bladder.
AB  - A rabbit model was used for the evaluation of a collagen-based biomatrix of small
      intestinal submucosa (SIS, COOK) in comparison to a biochemically reconstructed
      biomatrix for bladder tissue regeneration. Rabbits underwent partial cystectomy
      and cystoplasty with SIS patch graft or with a biochemically defined collagen
      biomatrix. The grafts of the regenerated bladder wall were harvested at different
      intervals and tissue regeneration was evaluated. The results of the SIS and
      biochemically defined biomatrix grafts were comparable. At harvesting, we found
      five bladder stones and encrustation of the biomatrix in 21/56 animals. No stone
      formation was observed in the control group. The results of the molecularly
      defined biomatrix are thus far comparable to SIS. Both matrices show good
      epithelialization and ingrowth of smooth muscle cells. Both biomatrices show
      considerable encrustation, which appears to disappear in time. The rabbit model
      is suitable for bladder tissue engineering studies as it is an easy model to use.
      In this model, besides tissue regeneration, also some of the clinical problems
      are seen such as encrustation of foreign body material in the bladder. These
      aspects are subject for further pre-clinical studies in this animal model.

PMID- 14697868
TI  - Capsule induction technique in a rat model for bladder wall replacement: an
      overview.
AB  - The search for a reliable technique for functional genitourinary tissue
      replacement remains a challenging task. The most recent advances in cell biology
      and tissue engineering have utilized various avascular and acellular collagen
      scaffolds with or without seeded cells. These techniques, however, are frequently
      complicated by tissue necrosis, contracture and resorption due to limited
      vascularization. We employed a new three-stage, evolving animal model with stage
      I optimizing the culture delivery vehicle, stage II employing a seeded
      vascularized capsule flap, and stage III adding a contractile matrix in the form
      of pedicled gracilis muscle prelaminated with autologous, in vitro-expanded
      urothelial cells to reconstruct an entire supratrigonal bladder-wall defect in
      rats.Specimens stained with hematoxylin and eosin (H&E), alpha(1)-actin staining,
      and a specific immunohistochemical staining (AE(1)&AE(3)-anticytoceratin
      monoclonal antibody stain) showed a continuous, multilayered, functioning
      urothelial lining along the transposed prelaminated gracilis flap in the animals
      of the final-stage experiment. Successful urinary reconstruction requires a
      contractile neoreservoir resistant to resorption over time and a stable,
      protective urothelial lining. We demonstrated that a gracilis muscle flap can be
      seeded with autologous cultured urothelial cells suspended in fibrin glue. This
      prelaminated flap can be safely transposed onto its pedicle and become
      successfully integrated into the remaining bladder wall, demonstrating urothelial
      lining and the potential to contract. Further studies in larger animals with
      urodynamic assessment is warranted to determine if this type of bladder-wall
      replacement technique is suitable for urinary reconstruction in humans.

PMID- 14697869
TI  - Animal models for intestinal tissue engineering.
AB  - Although total parenteral nutrition prevents patients with short bowel syndrome
      from dying of starvation, having short bowel remains a severely debilitating
      condition. The best current treatment for inadequate absorptive surface area is
      through intestinal transplantation. However, this therapy is associated with
      significant morbidity and patients suffer from consequences of long-term
      immunosuppression. Additionally, the numbers of organs are limited. A new
      frontier in medicine is the field of tissue engineering. We will review the
      progress of intestinal bioengineering with a focus on the use of animal models.
      Investigators initially used autologous tissue as a patch to study intestinal
      regeneration. Subsequent studies focused on the use of absorbable biomaterials as
      a patch for tissue ingrowth. The most novel methodology consists of seeding a
      resorbable scaffold and implanting this construct to observe the regeneration of
      neointestine. Successful creation of esophagus, stomach, small bowel and colon
      has been demonstrated. Although these studies are preliminary, the results
      suggest that tissue-engineered intestine will become a real therapeutic option in
      the not too distant future for patients with inadequate intestinal tissue.

PMID- 14697870
TI  - Individualised, micro CT-based finite element modelling as a tool for
      biomechanical analysis related to tissue engineering of bone.
AB  - Load-bearing tissues, like bone, can be replaced by engineered tissues or tissue
      constructs. For the success of this treatment, a profound understanding is needed
      of the mechanical properties of both the native bone tissue and the construct.
      Also, the interaction between mechanical loading and bone regeneration and
      adaptation should be well understood. This paper demonstrates that microfocus
      computer tomography (microCT) based finite element modelling (FEM) can have an
      important contribution to the field of functional bone engineering as a
      biomechanical analysis tool to quantify the stress and strain state in native
      bone tissue and in tissue constructs. Its value is illustrated by two cases: (1)
      in vivo microCT-based FEM for the analysis of peri-implant bone adaptation and
      (2) design of biomechanically optimised bone scaffolds. The first case involves a
      combined animal experimental and numerical study, in which the peri-implant bone
      adaptive response is monitored by means of in vivo microCT scanning. In the
      second case microCT-based finite element models were created of native trabecular
      bone and bone scaffolds and a mechanical analysis of both structures was
      performed. Procedures to optimise the mechanical properties of bone scaffolds, in
      relation to those of native trabecular bone are discussed.

PMID- 14697871
TI  - Biomechanical considerations of animal models used in tissue engineering of bone.
AB  - Tissue engineering combines the aspects of cell biology, engineering, material
      science, and surgery to generate new functional tissue, and provides an important
      approach to the repair of segmental defects and in restoring biomechanical
      function. The development of tissue-engineering strategies into clinical
      therapeutic protocols requires extensive, preclinical experimentation in
      appropriate animal models. The ultimate success of any treatment strategy must be
      established in these animal models before clinical application. It is clear that
      the demands of the biological and mechanical environment in the clinical repair
      of critical size defects with tissue-engineered materials is significantly
      different from those existing in experimental animals. The major considerations
      facing any tissue-engineering testing logic include the choice of the defect, the
      animal, the age of the animal, the anatomic site, the size of the lesion, and
      most importantly, the micro-mechanical environment. With respect to biomechanical
      considerations when selecting animals for tissue- engineering of bone, it is
      evident that no common criteria have been reported. While in smaller animals due
      to size constraint only structural properties of whole bones can be measured, in
      larger animals and humans both material properties and structural properties are
      of interest. Based on reported results, comparison between the tissue-engineered
      bone across species may be of importance in establishing better model selection
      criteria. It has already been found that the deformation of long bones is fairly
      constant across species, and that stress levels during gait are dependent on the
      weight of the animal and the material properties of the bone tissue. Future
      research should therefore be geared towards developing better biomechanical
      testing systems and then finding the right animal model for the existing
      equipment.

PMID- 14697872
TI  - Animal models of tendon and ligament injuries for tissue engineering
      applications.
AB  - Animal modeling continues to be an important component to the critical evaluation
      of new techniques to treat tendon and ligament injuries. Appropriate choice and
      analysis of these models is essential. Factors that should be considered in
      assessing a potential model include the tissue type (ligament versus tendon and
      intrasynovial versus extrasynovial), the type of injury to be modeled, the
      techniques of measuring the response to treatment, the ease of comparison to
      previously published models and finally, the ease of translation to human trials
      and eventually to clinical usage.

PMID- 14697873
TI  - Moral imagination in tissue engineering research on animal models.
AB  - Animal experimentation is an integrated part of tissue engineering research. This
      paper investigates what scientists conducting such experimentation should
      reasonably take into consideration from an ethical point of view. It is argued
      that scientists should use their moral imagination in making fundamental ethical
      choices, in reflecting on legal regulation, in taking public opinion seriously,
      and in balancing human benefit and animal harm as expected outcomes of the
      experiments.

PMID- 14697874
TI  - Monoamine oxidases: molecular, pharmacological and neurotoxicological aspects. A
      tribute to Professor Merton Sandler.

PMID- 14697875
TI  - My fifty years (almost) of monoamine oxidase.

PMID- 14697876
TI  - Progress in monoamine oxidase (MAO) research in relation to genetic engineering.
AB  - Monoamine oxidase (MAO) is an enzyme that oxidizes various physiologically and
      pathologically important monoamine neurotransmitters and hormones such as
      dopamine, noradrenaline, adrenaline, and serotonin. Two types of MAO, i.e. type A
      (MAO-A) and type B (MAO-B), were first discovered pharmacologically. MAO-A is
      inhibited by clorgyline; and MAO-B, by deprenyl. cDNAs MAO-A and MAO-B were
      cloned and their structures determined. MAO-A and MAO-B are made of similar but
      different polypeptides and encoded by different nuclear genes located on the X
      chromosome (Xp11.23). MAO-A and MAO-B genes consist of 15 exons with identical
      intron-exon organization, suggesting that they were derived from a common
      ancestral gene. Both enzymes require a flavin cofactor, flavin adenine
      dinucleotide (FAD), which binds to the cysteine residue of a pentapeptide
      sequence (Ser-Gly-Gly-Cys-Tyr). Both enzymes exist on the outer membrane of
      mitochondria of various types of cells in various tissues including the brain. In
      humans, MAO-A is abundant in the brain and liver, whereas the liver, lungs and
      intestine are rich in MAO-B. MAO-A oxidizes noradrenaline and serotonin; and MAO
      B, mainly beta-phenylethylamine. In the human brain, MAO-A exists in
      catecholaminergic neurons, but MAO-B is found in serotonergic neurons and glial
      cells. MAO-A knockout mice exhibit increased serotonin levels and aggressive
      behavior, whereas MAO-B knockout mice show little behavioral change. The gene
      knockout mice of MAO-A or MAO-B, together with the observation that some humans
      lack MAO-A, MAO-B, or both have contributed to our understanding of the function
      of MAO-A and MAO-B in health and disease. MAO-A and MAO-B may be closely related
      to various neuropsychiatric disorders such as depression and Parkinson's disease,
      and inhibitors of them are the subject of drug development for such diseases.

PMID- 14697877
TI  - Cloning, after cloning, knock-out mice, and physiological functions of MAO A and
      B.
AB  - Cloning of MAO A and B has demonstrated clearly that MAO A and B are coded by
      different proteins with 70% amino acid identity. With the MAO A and B cDNA
      clones, we showed the tissue distribution and genomic structure of MAO A and B,
      the latter suggesting that they are derived from the same ancestral gene. The
      active sites, the role of cysteine residues, the three-dimensional models and the
      mitochondria targeting domains of both isoenzymes have been established. The
      transcriptional regulation of MAO A and B has been studied. MAO A KO mice showed
      increased levels of serotonin (5-HT), norepinephrine (NE), dopamine (DA) whereas
      MAO B KO mice showed increased phenylethylamine (PEA) levels only. Both MAO A and
      B KO mice showed increased response to stress. MAO A KO mice showed increased
      emotional learning and memory and aggressive behavior, but the vesicular
      monoamine transporter (VMAT2), 5-HT1A, 5-HT2A and 5-HT2C receptors were down
      regulated. 5-HT2A antagonist, ketanserin and MDL100907 were able to abolish the
      aggression, suggesting that the aggressive behavior may be mediated by 5-HT2A
      receptor. In contrast, MAO B KO mice are resistant to MPTP, a toxin which induces
      Parkinson's syndromes. Studies of these mice suggest that MAO A and B have
      distinct biochemical and physiological functions.

PMID- 14697878
TI  - Organization of MAO A and MAO B promoters and regulation of gene expression.
AB  - Monoamine oxidase (MAO) A and B play important roles in the metabolism of
      catecholamines and xenobiotics in the central nervous system and peripheral
      tissues. The ubiquitous presence of low level of MAO in all cells suggests
      essential functional for house keeping. Higher level of expression of MAO A and B
      also were observed in tissue and cell specific manner. The core promoter of human
      MAO A and B promoters have been characterized. Sp1 binding motifs were present in
      both promoters which constituted the major binding sites for Sp1 and Sp1-like
      family transcription factor binding, and other interaction proteins like Egr-1 in
      MAO B promoter. The presence of repeat units within the 2 kb human MAO A promoter
      which is associated with promoter activity and enzymatic activity in human
      fibroblast culture provided a tool to study human population with abnormal
      behaviors related to serotonin and other neurotransmitters. Conflicting results
      were reported from these studies due to the lack of basic understanding of MAO A
      promoter and the factors such as glucocorticoid which influences MAO A activity.
      Hopefully the enthusiasm will lead to more reliable tools to identify the major
      factor which caused the large difference in MAO A activity among human
      population. The overlapping Sp1/Egr-1/Sp1 binding site within MAO B promoter has
      been identified as the responsible element for PMA response. MAO B expression is
      selectively induced by the activation of protein kinase C and MAPK signal
      pathway.

PMID- 14697879
TI  - Computer modelling and visualization of active site of monoamine oxidases.
AB  - In spite of significant progress in MAO research culminating in the
      crystallization of the MAO B, many structure-functional aspects of these enzymes
      still require better characterization. Computer modelling of the
      substrate/inhibitory binding region of the active site includes consensus overlay
      of several series of fully reversible and/or tightly bound inhibitors onto a
      rigid referent inhibitor(s). The shape of resultant mould obviously reflects
      spatial characteristic features of the substrate/inhibitor binding region. The
      comparison of the active site mould of MAO B with its crystal structure revealed
      correctness of this approach. The resultant moulds may be effectively used for
      virtual screening of molecular databases for new lead-structures. Using this
      approach we have found several selective MAO A inhibitors in databases and these
      compounds have never been tested for MAO inhibitory activity.

PMID- 14697880
TI  - Modeling of human monoamine oxidase A: from low resolution threading models to
      accurate comparative models based on crystal structures.
AB  - The recently published crystal structure of monoamine oxidase (MAO) B was a major
      breakthrough for structural and functional understanding of flavin containing
      amine oxidases: it opens a new era of research and provides new opportunities to
      those interested in the biochemistry and pharmacology of those important drug
      targets. In particular, it allowed accurate modeling of human MAO A, both
      proteins sharing over 70% sequence identity. In the present contribution, we
      summarize the efforts made in order to obtain structural information on the human
      MAO A, including sequence analysis, secondary structure predictions, and
      preliminary models obtained by fold recognition and comparative modeling based on
      proteins sharing low sequence identity.

PMID- 14697881
TI  - The FAD binding sites of human monoamine oxidases A and B.
AB  - The structural details of the interactions of the covalent 8alpha-S-cysteinyl-FAD
      with the protein moiety in monoamine oxidase B (MAO B) based on the MAO B crystal
      structure are described. The dinucleotide is bound to the protein in an extended
      conformation with the majority of the bonds to the protein identified as hydrogen
      bonds with amino acid side chains, amide bonds, and water molecules. Since those
      amino acids interacting with the FAD are conserved in monoamine oxidase A (MAO
      A), it is proposed that the FAD binding site in MAO A is quite similar to that in
      MAO B. The redox-active isoalloxazine ring is buried in the protein without
      direct access to bulk solvent. An electrostatic interaction is observed between
      the anionic pyrophosphate moiety and Arg42. The normally flat oxidized flavin
      ring is in a bent, puckered conformation in the MAO B binding site which is
      suggested to contribute to its reactivity in catalysis. This structural
      information is then used to explain previous studies on flavin analog
      incorporation into either MAO B or into MAO A.

PMID- 14697882
TI  - Conserved elements of the cytochrome P-450 superfamily found in monoamine oxidase
      B.
AB  - Monoamine oxidases A and B (MAO A and B) are the major enzymes in mammals that
      catalyze the oxidative deamination or oxidation of neurotransmitters, peripheral
      vasoactive amines, and xenobiotics (e.g. MPTP). Although these enzymes are among
      the most widely studied flavoproteins, their integral association with the outer
      mitochondrial membrane has deterred knowledge of their structures until recent
      work yielded the three-dimensional structure of MAO B [Nat. Struct. Biol. 9
      (2002) 22]. In our study, we compared the primary sequence in different regions
      of MAO B to those in selected proteins of known structure, including cytochrome P
      450. Using site-directed mutagenesis [Prog. Nucleic Acid Res. Mol. Biol. 65
      (2001) 129], we have identified three amino acids residues (Phe 423, Glu 427, and
      Thr 428) that appear to play a role in generating catalytically active MAO B.
      However, examination of models of the MAO B structure show that these residues
      lie outside the substrate binding site. Thus, it appears that Phe 423, Glu 427
      and Thr 428 do not directly affect the active site, but they could modulate
      activity through an independent function such as non-covalent binding of FAD
      during synthesis of the MAO B polypeptide chain.

PMID- 14697883
TI  - Platelet monoamine oxidase, personality and alcoholism: the rise, fall and
      resurrection.
AB  - The history of research on the association between platelet monoamine oxidase
      (MAO) activity and personality traits, such as sensation seeking and
      impulsiveness, is reviewed. The effects of MAO-inhibiting compounds in cigarette
      smoke for the interpretation of this association are discussed. Recent results
      confirming a true association between platelet MAO activity and personality are
      presented. From a clinical point of view, this association has had its greatest
      impact on the understanding of the nature of constitutional factors making
      individuals vulnerable for e.g. substance abuse and the link between low platelet
      MAO activity and type 2 alcoholism, recently confirmed on non-human primates, is
      discussed. The molecular mechanisms underlying the association between platelet
      MAO and behaviour are discussed and evidence that common transcriptional factors,
      e.g. within the AP-2 family, regulating both the expression of platelet MAO and
      components of central monoaminergic systems, such as synthetizing enzymes,
      receptors and transporters, are presented. A hypothesis is put forward, that such
      common transcription factors may not directly regulate platelet MAO expression,
      but rather mitochondrial number or outer membrane surface.

PMID- 14697884
TI  - Link between monoamine oxidase and nitric oxide.
AB  - For the last few decades, there has been extensive research and supporting
      evidence for the role of monoamine oxidase (MAO) activity and its' possible
      manipulation in the pathophysiology of neurodegenerative disorders. Although, the
      role of dopaminergic, noradrenergic and serotonergic systems in central nervous
      system (CNS) and neurodegenerative diseases have been mostly demonstrated, the
      intrinsic mechanisms in these systems with relation to other molecules in CNS
      have received less attention. A more recently discovered molecule, nitric oxide
      (NO) has also gained attraction in a number of physiological and pathological
      states. Much of this attraction is due to the role of NO as a
      neurotransmitter/neuromodulator in the CNS. This review will describe our current
      state of knowledge about the established biochemical mechanisms of MAO and NO,
      with particular emphasis on aging and neurodegenerative disorders. Possible
      intrinsic mechanisms which are likely to be of crucial importance will also be
      discussed and a link in between will be proposed based on the evidence derived
      from recent basic and clinical research.

PMID- 14697885
TI  - Neurotoxicity of MAO metabolites of catecholamine neurotransmitters: role in
      neurodegenerative diseases.
AB  - The monoamine oxidase (MAO) metabolites of norepinephrine (NE) or epinephrine
      (EPI) and of dopamine (DA) are 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL) and
      3,4-dihydroxyphenylacetaldehyde (DOPAL), respectively. The toxicity of these
      catecholamine (CA) MAO metabolites was predicted over 50 years ago. However,
      until our recent chemical synthesis of these CA aldehyde metabolites, the
      hypothesis about their toxicity could not be tested. The present paper reviews
      recent knowledge gained about these compounds. Topics to be reviewed include:
      chemical synthesis and properties of DOPEGAL and DOPAL; in vitro and in vivo
      toxicity of CA aldehydes; subcellular mechanisms of toxicity; free radical
      formation by DOPEGAL versus DOPAL; mechanisms of accumulation of CA aldehydes in
      Alzheimer's disease (AD) and Parkinson's disease (PD) and potential therapeutic
      targets in Alzheimer's disease and Parkinson's disease.

PMID- 14697886
TI  - Tetrahydropapaveroline in Parkinson's disease and alcoholism: a look back in
      honor of Merton Sandler.
AB  - Although Dr. Merton Sandler's extensive and vigorous research program over the
      years has been concerned mainly with classical biogenic amines, monoamine oxidase
      (MAO), and MAO inhibitors, he and his group contributed a significant early
      Parkinson's disease-related study of a non-classical or "aberrant" biogenic
      amine. The formation and production of this amine, the dopamine-derived mammalian
      alkaloid, tetrahydropapaveroline (THP), is in fact dependent on MAO activity. As
      reviewed here, that study provided the groundwork for and indeed stimulated many
      later investigations of mammalian alkaloids in numerous laboratories around the
      world.

PMID- 14697887
TI  - Neurotoxicity, oxidative stress and cerebrovascular disorders.

PMID- 14697888
TI  - Monoamine oxidase (MAO) in human peripheral tissues.

PMID- 14697889
TI  - Immunohistochemical localization of monoamine oxidase type B in the taste bud of
      the rat.
AB  - We have used immunohistochemistry to examine the subcellular localization of
      monoamine oxidase type B (MAO-B) in the taste bud of the rat circumvallate
      papilla. Electron microscopy showed that MAO-B was localized to the outer
      membranes of mitochondria in nerve terminals of afferent and efferent fibers, as
      well as in taste bud cells. MAO-B also existed on the mitochondrial outer
      membranes within myelinated and unmyelinated axons in the lamina propria beneath
      the taste bud. It is suggested that MAO-B-containing mitochondria are localized
      in peripheral branches and their terminals of sensory neurons for taste. The
      present study is the first to reveal the localization of MAO-B in sensory organs.

PMID- 14697890
TI  - Monoamine oxidase expression during development and aging.
AB  - Monoamine oxidase (MAO) isoenzymes play a major role in regulating the
      concentration of several bioactive amines, including serotonin and
      catecholamines. Both in the nervous system and in peripheral organs, MAOs can
      potentially modulate all the processes involving these bioactive amines. In the
      present article, we review some of the most significant articles published so far
      on changes in MAOs during development and aging. The data available on
      development refer mainly to the mammal brain at fetal and post-fetal stages. Very
      little work has been done on studying MAO ontogenesis during early development,
      that is, at stages prior to organogenesis, and what has been done refers to non
      mammal vertebrates such as fish, amphibians and birds. MAO A and MAO B changes
      have been measured as values of enzymatic activity, as amount of protein or, more
      rarely, as amount of mRNAs. A knowledge of MAO developmental changes not only
      provides a basis for the investigation of factors regulating MAO expression, but
      can also contribute to a better understanding of the possible trophic and/or
      morphogenetic role of monoaminergic neurotransmitters in the developing brain.
      Transgenic mice lacking MAO A and rodents treated with MAO inhibitors during
      gestation have been very useful in this second case. The investigations of
      changes in MAO A and MAO B during aging in the literature refer mostly to humans,
      mice and rats. Interest in studies on aging is stimulated, among other things, by
      the observation that age-related diseases leading to neurodegenerative phenomena
      could be accompanied by changes in MAO activity.

PMID- 14697891
TI  - The effect of diabetes mellitus on the morphology and physiology of monoamine
      oxidase in the pancreas.
AB  - Monoamine oxidase (MAO) is an ubiquitous, non-soluble, membrane-bound enzyme,
      located in the outer membrane of mitochondria. MAO consists of two subtypes, MAO
      A and MAO-B, depending on their substrates and sensitivity to inhibitors. MAO
      consists of two units joined together by a disulphide bond. The two units of MAO
      and flavin adenine dinucleotide (FAD) form a polymer in the outer membrane of
      mitochondria. The function of MAO-A is highly dependent on the lipid constituent
      of mitochondrial membrane, whereas the function of MAO-B does not depend on the
      lipid status of mitochondrial membrane. Hydrogen peroxide and ammonia are
      generated during MAO-induced metabolism of its substrates. MAO and its substrates
      are present in both the exocrine as well as the endocrine parts of the pancreas.
      In the islet of Langerhans, MAO-A is observed in about 50% of the cells, whereas
      MAO-B is less abundant and located mainly in the periphery of pancreatic islets.
      MAO-B is also demonstrated in centroacinar cells and in pancreatic ducts.
      Electron microscopy studies suggest that MAO is co-localised with insulin in
      secretory granules of pancreatic beta cells. Pharmacologically, beta-2
      adrenoreceptors agonists such as terbutaline can stimulate MAO activity. In
      contrast, cholinergic muscarinic stimulation does not affect islet MAO activity.
      MAO activity in pancreatic tissue is significantly reduced in diabetes. This
      decrease in MAO activity is associated with an increase in pancreatic tissue
      levels of adrenaline (ADR) and noradrenaline (NA). Studies on the level of 5
      hydroxyindoleacetic acid of pancreatic tissues suggest that serotonin level is
      also increased in diabetics. Many studies show that MAO inhibits insulin
      secretion. However, some of its substrates including, serotonin, adrenaline and
      noradrenaline have been shown to stimulate insulin secretion. In conclusion, the
      activity and subcellular localisation of MAO suggests that MAO may play an
      important role in pancreatic beta cell function and hence in the pathogenesis of
      diabetes mellitus.

PMID- 14697892
TI  - Metabolism of monoamines in invertebrates: the relative importance of monoamine
      oxidase in different phyla.
AB  - A review of the occurrence of monoamine oxidase activity in invertebrates is
      presented. In contrast to vertebrates, invertebrates use a variety of enzymatic
      routes to metabolise monoamines. These routes include N-acetylation, gamma
      glutamyl conjugation, sugar conjugation, sulphation, beta-alanyl conjugation as
      well as oxidative deamination. Some of these enzymatic routes appear to be
      strictly catabolic whereas others result in metabolites used for structural and
      pigmentation purposes. The development of the various catabolic routes for
      monoamines in different groups of invertebrates may be dependent on the physical
      requirements of the diverse excretory organs used by these animals.

PMID- 14697893
TI  - Tribulin and endogenous MAO-inhibitory regulation in vivo.
AB  - Tribulin is the name given to a family of endogenous nonpeptide substances which
      inhibit monoamine oxidase (MAO) and benzodiazepine binding. It is widely
      distributed in mammalian tissues and body fluids, and exhibit some species and
      tissue variations. Several components selectively inhibiting MAO A, MAO B,
      central and peripheral benzodiazepine binding (tribulins A, B, BZc and BZp,
      respectively) have been recognised. Tribulin A represents some tissue-specific
      metabolites of trace amines, whereas isatin is the major component of tribulin B.
      Tribulin content increases in brain under conditions of stress and anxiety and is
      reduced under sedation. Changes in tribulin content in the brain are accompanied
      by corresponding changes in the content of monoamines and their acidic
      metabolites, and also by altered susceptibility of MAO to specific mechanism
      based inhibitors. This suggests that tribulin is involved in MAO inhibitory
      regulation in vivo.

PMID- 14697894
TI  - Dopamine-derived salsolinol derivatives as endogenous monoamine oxidase
      inhibitors: occurrence, metabolism and function in human brains.
AB  - Salsolinol, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, is an
      endogenous catechol isoquinoline detected in humans by M. Sandler. In human
      brain, a series of catechol isoquinolines were identified as the condensation
      products of dopamine or other monoamines with aldehydes or keto-acids. Recently
      selective occurrence of the (R)enantiomers of salsolinol derivatives was
      confirmed in human brain, and they are synthesized by enzymes in situ, but not by
      the non-enzymatic Pictet-Spengler reaction. A (R)salsolinol synthase catalyzes
      the enantio-specific synthesis of (R)salsolinol from dopamine and acetaldehyde,
      and (R)salsolinol N-methyltransferase synthesizes N-methyl(R)salsolinol, which is
      further oxidized into 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion by non
      enzymatic and enzymatic oxidation. The step-wise reactions, N-methylation and
      oxidation, induce the specified distribution of the N-methylated and oxidized
      derivatives in the human nigro-striatum, suggesting that these derivatives may be
      involved in the function of dopamine neurons under physiological and pathological
      conditions. As shown by in vivo and in vitro experiments, salsolinol derivatives
      affect the levels of monoamine neurotransmitters though the inhibition of enzymes
      related in the metabolism of catechol- and indoleamines. In addition, the
      selective neurotoxicity of N-methyl(R)salsolinol to dopamine neurons was
      confirmed by preparation of an animal model of Parkinson's disease in rats. The
      involvement of N-methyl(R)salsolinol in the pathogenesis of Parkinson's disease
      was further indicated by the increase in the N-methyl(R)salsolinol levels in the
      cerebrospinal fluid and that in the activity of its synthesizing enzyme, a neural
      (R)salsolinol N-methyltransferase, in the lymphocytes prepared from parkinsonian
      patients. N-methyl(R)salsolinol induces apoptosis in dopamine neurons, which is
      mediated by death signal transduction in mitochondria. In addition, salsolinol
      was found to function as a signal transmitter for the prolactin release in the
      neuro-intermediate lobe of the brain. These results are discussed in relation to
      role of dopamine-derived endogenous salsolinol derivatives as the regulators of
      neurotransmission, dopaminergic neurotoxins and neuro-hormonal transmitters in
      the human brain.

PMID- 14697895
TI  - Comparative study of the effects of isatin, an endogenous MAO-inhibitor, and
      selegiline on bradykinesia and dopamine levels in a rat model of Parkinson's
      disease induced by the Japanese encephalitis virus.
AB  - We previously reported that exogenously administered isatin, an endogenous
      monoamine oxidase (MAO) inhibitor, significantly increased acetylcholine (ACh)
      and dopamine (DA) levels in the rat striatum. Selegiline [(-)-deprenil] was
      developed as a MAO-B inhibitor more than 30 years ago and widely used in the
      treatment of Parkinson's disease. Effects of isatin or selegiline were
      investigated in Japanese encephalitis virus (JEV)-induced post-encephalitic
      parkinsonism rats by a pole test for detecting motor activity and by the
      determination of biogenic amine levels. Motor activity of JEV-induced rats
      receiving isatin (100 mg/kg per day for 1 week, i.p.) or selegiline (0.2 mg/kg
      per day for 1 week, i.p.) was significantly improved compared with that of
      untreated JEV-infected rats. Both isatin and selegiline prevented the decrease in
      striatal DA levels in JEV-rats. The increased turnover of DA (DOPAC/DA) induced
      by JEV was significantly inhibited by isatin, but not by selegiline. These
      results suggested that exogenously administered isatin and selegiline can improve
      JEV-induced parkinsonism by increasing DA concentrations in the striatum.

PMID- 14697896
TI  - Clinical pharmacology of MAO inhibitors: safety and future.
AB  - In this article, we review the clinical pharmacology of monoamine oxidase
      inhibitors (MAOIs). Now, MAOIs are used for the treatment of depressive
      disorders, anxiety disorders, Parkinson's disease, and Alzheimer's disease. The
      selective monoamine oxidase-B inhibitor selegiline and the selective and
      reversible inhibitor of monoamine oxidase-A (RIMA) moclobemide are free from the
      hypertensive crisis, the so-called "cheese effect." Therefore, selective MAO-B
      inhibitors and RIMAs hold promise as safer alternatives to classical MAOIs. It is
      clear that much remains to be investigated with regard to the clinical
      pharmacology of MAOIs. It seems obvious that a greater understanding of the
      pharmacodynamics and pharmacokinetics of MAOIs could result in improved treatment
      of the patients in the future.

PMID- 14697897
TI  - Monoamine oxidase and head-twitch response in mice. Mechanisms of alpha
      methylated substrate derivatives.
AB  - It is well known that head-twitch response (HTR) in mice represents
      hallucinations, since administration of lysergic acid diethylamide (LSD) produces
      hallucinations in humans, and the HTR in mice is induced by administration of LSD
      as a hallucinogen. The HTR is produced by excitation of 5-hydroxytryptamine (5
      HT)2A receptors. In this paper, we review the mechanisms of HTR induced by
      various drugs such as 5-HT precursor, 5-HT receptor agonist, 5-HT releaser,
      hallucinogenic compounds, benzodiazepins and cannabinoid. The response induced by
      HTR-inducers is significantly enhanced by combined treatment with a non-selective
      form of monoamine oxidase (MAO) inhibitor. Thus, the relationship between MAO
      activity and HTR caused by these drugs (especially, alpha-methylated analogous
      compounds which 5-fluoro-alpha-methyltryptamine, 6-fluoro-alpha-methyltryptamine
      and p-hydroxyamphetamine) is presented in detail.

PMID- 14697898
TI  - (-)-Deprenyl, a selective MAO-B inhibitor, with apoptotic and anti-apoptotic
      properties.
AB  - (-)-Deprenyl (selegiline) is an irreversible inhibitor of monoamine oxidase (MAO)
      B, which was discovered in 1962 and become the "golden standard" of MAO research.
      Like the other MAO-B inhibitors, it was synthesized as an antidepressant, but in
      a selective MAO-B inhibitory dose it does not act in depression. It is used in
      the treatment of Parkinson's disease. (-)-Deprenyl potentiates the effect of
      dopamine, it has antioxidant activity and prevents the toxicity of the
      dopaminergic (6-OH-dopamine; 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine
      (MPTP)), the noradrenergic (DSP-4) and cholinergic (AF64A) neurotoxins after pre
      treatment. When (-)-deprenyl was administered with levodopa in a long-term
      treatment of Parkinsonian patients, it induces adverse events (nausea, dizziness,
      confusion, hallucination, insomnia and cardiovascular changes), which could be
      due to dopamine potentiation in dopaminergic systems (limbic system), other than
      the nigrostriatal pathway. (-)-Deprenyl in much lower concentrations needed to
      induce MAO-B inhibition (10(-9) to 10(-13) M) potently inhibits MPTP or serum
      withdrawal induced apoptosis in tissue cultures of neuro-ectodermal origin (PC12,
      M1, M2058). The (+)-enantiomer of deprenyl lacks of this property. The anti
      apoptotic activity of (-)-deprenyl can be prevented by inhibiting the metabolism
      of the drug with SKF-525A pre-treatment, which suggests that some of the
      presently unknown metabolites could be responsible for the anti-apoptotic
      activity. In high concentration (10(-3) M), (-)-deprenyl and its metabolites
      induce apoptosis in tissue cultures without serum withdrawal (biphasic action).
      Our findings support the view that 100, or even 1000 times lower dose of (-)
      deprenyl can be offered in human therapy to protect, or slow down neuronal
      degeneration, than it is presently used. With low dose of the drug the
      dopaminergic adverse events could be avoided, while anti-apoptotic activity might
      be preserved.

PMID- 14697899
TI  - Therapeutic applications of selective and non-selective inhibitors of monoamine
      oxidase A and B that do not cause significant tyramine potentiation.
AB  - The major side effect with the use of first generation of non selective monoamine
      oxidase (MAO) inhibitors as neuropsychiatric drugs was what became known as the
      "cheese reaction". Namely, potentiation of sympathomimetic activity of ingested
      tyramine present in cheese and other food stuff, resulting from its ability to
      release noradrenaline, when prevented from metabolism by MAO. The identification
      of two forms of MAO, termed types A and B and their selective irreversible
      inhibitors resolved some of this problems. However irreversible MAO-A inhibitors
      continue to induce a cheese reaction, whereas MAO-B inhibitors at their selective
      dosage did not and led to introduction of L-deprenyl (selegiline) as an anti
      Parkinson drug, since dopamine is equally well metabolized by both enzyme forms.
      The cheese reaction is a consequence of inhibition of MAO-A, the enzyme
      responsible for metabolism of noradrenaline and serotonin, located in peripheral
      adrenergic neurons. The consequence of these findings were the development of
      reversible MAO-A inhibitors (RIMA), moclobemide and brofaromin, as
      antidepressants and possible anti-Parkinson activity, with limited tyramine
      potentiation, since the amine can displace the inhibitor from its binding site on
      the enzyme. It has always been deemed a greater pharmacological advantage to
      inhibit both forms of the enzymes to get the full functional activities of the
      amine neurotransmitters, and without inducing a "cheese reaction". This was not
      possible until recently, with the development of the novel cholinesterase-brain
      selective MAO-AB inhibitor, TV3326 (N-propargyl-(3R)-aminoidnan-5-yl-ethyl
      methylcarbamate hemitartiate), a carbamate derivative of the irreversible MAO-B
      inhibitor anti-Parkinson drug, rasagiline. This drug is a brain selective MAO-A
      and B inhibitor, with little inhibition of liver and small intestine enzymes.
      Pharmacologically it has limited tyramine potentiation, very similar to
      moclobemide and being a MAO-AB inhibitor it has the antidepressant, anti
      Parkinson and anti-Alzheimer activities in the respective models used to develop
      such drugs.

PMID- 14697900
TI  - On the binding of monoamine oxidase inhibitors to some sites distinct from the
      MAO active site, and effects thereby elicited.
AB  - Many inhibitors of monoamine oxidase, particularly those developed during the
      past three decades, are often referred to as being "selective" for one or other
      isoform of the enzyme. However true this may be, selectivity within the EC
      1.4.3.4 family does not preclude the possibility of interactions of these drugs
      with other proteins unrelated to monoamine oxidase. Indeed, evidence exists which
      either suggests or demonstrates directly that many of these inhibitors do
      interact with, and affect the behaviour of, other enzymes, receptor systems and
      uptake pumps, with potentially interesting consequences, desirable or otherwise,
      for the patient or the pharmacologist. An overview of many such interactions, and
      speculation upon some of the possible consequences, are provided in this review.

PMID- 14697901
TI  - Monoamine oxidase inhibition and CNS immunodeficiency infection.
AB  - HIV invades CNS subcortical areas, particularly the dopamine-rich basal ganglia
      and induces a subcortical dementia. Data suggest that the basal ganglia
      dysfunction plays a critical role in the neuropsychiatric manifestation of HIV
      infection. Therefore, therapeutic approaches for HIV dementia nowadays wish to
      include apart from the highly active antiretroviral therapy (HAART) also
      adjunctive medication. In this short article, we report briefly on neurotoxicity
      associated with the immunodeficiency virus and discuss the effects of selegiline,
      a monoamine oxidase inhibitor which enhances dopamine availability in CNS on
      immunodeficiency virus-induced neurological disease.

PMID- 14697902
TI  - Monoamine oxidase-B inhibition in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia in late life. There
      is still no clear-cut consensus whether this disease involves genetic or
      environmental factors or both. There is a great need to find a way to delay the
      disease, as delaying the onset of the disease will bring a great relieve on
      social and medical resources. The monoamine oxidase-B (MAO-B) inhibitors were
      shown to be effective in treating Parkinson's disease and possibly AD, with
      concomitant extension of life span. This article gives a short review on MAO-B
      inhibitors and their mechanism for neuroprotective effects in AD.

PMID- 14697903
TI  - Tobacco leaf, smoke and smoking, MAO inhibitors, Parkinson's disease and
      neuroprotection; are there links?
AB  - The potential neuroprotective properties of monoamine oxidase B (MAO-B)
      inhibitors have been of interest in part because of the role that this enzyme
      plays in the bioactivation of the parkinsonian inducing neurotoxin 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP). Interestingly, tobacco smokers have
      lowered levels of brain and blood platelet MAO-B activity and a well documented
      lowered incidence of Parkinson's disease (PD) compared to non-smokers. This
      correlation has led to the intriguing question of whether there are possible
      relationships between smoking, MAO-B activity and PD. Recent studies have
      evaluated specific components of tobacco smoke for their MAO inhibiting and
      neuroprotective properties. This chapter summarizes the relevant literature
      relating to the basic questions in these areas. We have undertaken studies to
      identify possible inhibitors of MAO-B in the tobacco leaf and tobacco smoke and
      have evaluated one such compound in the MPTP PD mouse model. In this chapter we
      report on the results of these studies and present a discussion of potential
      avenues of research and their implication with respect to PD, smoking and
      monoamine oxidase.

PMID- 14697904
TI  - A screening system of prodrugs selective for MAO-A or MAO-B.
AB  - We synthesized several prodrugs of glycine and gamma-aminobutyric acid. In order
      to establish a screening system from the prodrugs of selective activity to MAO-A
      or MAO-B, we examined purification conditions such as solubilization with Triton
      X-100, precipitation with ammonium sulfate, gel filtration and anion exchange
      chromatography. MAO-B was purified from various tissues such as guinea pig brain,
      kidney and spleen. MAO-A from human placenta without MAO-B was unstable in above
      purifications and used as crude. At each purification step, we checked
      sensitivity of the enzyme to specific inhibitors by developing a convenient
      fluorescence assay, in which hydrogen peroxide produced by the enzyme was reacted
      with p-hydroxyphenylpropionic acid. A fluorescence microplate reader measured a
      fluorescence of the fluorescent product from p-hydroxyphenylpropionic acid with
      horseradish peroxidase. In comparison with milacemide, N,N-bis(carbamoylmethyl)-N
      pentylamine was the best and exclusive substrate for MAO-B. 2-N
      (phenylethylamino)-acetoamide was the good substrate for MAO-A and MAO-B same as
      milacemide. 4-N-(n-pentylamino)-butyric acid and 4-(N-phenylethylamino)-butyric
      acid were the moderate substrates for both enzymes, which should release gamma
      aminobutyric acid. These drugs will be new leading compounds.

PMID- 14697905
TI  - Semicarbazide-sensitive amine oxidases: enzymes with quite a lot to do.
AB  - The semicarbazide-sensitive amine oxidases (SSAO) (EC 1.4.3.6) were believed to
      be detoxifying enzymes, primarily involved in the oxidative deamination of
      endogenous amines, such as methylamine and aminoacetone, together with some
      xenobiotic amines. However, it appears that the reaction products may have
      important signalling functions in the regulation of cell development and glucose
      homeostasis. Furthermore, enzyme, from some sources, behaves as a cellular
      adhesion protein under inflammatory and it may also be involved in lipid
      transport. This review considers what is known about the activities and potential
      functions of this hardworking protein.

PMID- 14697906
TI  - Amine oxidases and tumors.
AB  - The physiological function in living organisms of amine oxidases, is not
      completely established but is certainly related to the biogenic amines metabolism
      and therefore involved in essential processes such as the cell growth and
      differentiation. A correlation between degree of tumor malignancy and level of AO
      activity has been reported. The catalytic products of oxidative deamination of
      amines (hydrogen peroxide and aminoaldehyde) exert a cytotoxic effect and are
      considered cell growth inhibitors. The biogenic amines in same way could be
      considered in the cells as both poisons and protectors. A balance of oxidant and
      antioxidant enzymes appears to be very important in carcinogenesis and cell
      growth regulation.

PMID- 14697907
TI  - Selective inhibitors of membrane-bound semicarbazide-sensitive amine oxidase
      (SSAO) activity in mammalian tissues.
AB  - Semicarbazide-sensitive amine oxidase (SSAO, EC 1.4.3.6) is a group of enzymes
      highly sensitive to inhibition by semicarbazide. This high sensitivity
      distinguishes these enzymes from monoamine oxidase (MAO). Various mammalian
      tissues contain membrane-bound SSAO which metabolizes only the primary
      monoamines. Vascular and non-vascular smooth muscle cells have particularly high
      SSAO activity, but recently the enzyme activity has also been found in non
      vascular smooth muscle cells. The substrate specificity of SSAO shows
      considerable species-related variations. A variety of compounds inhibiting MAO
      activity has also been identified as SSAO inhibitors. Among inhibitors, there is
      no specific SSAO inhibitor so far tested. Many studies reinforce the conclusion
      that inhibitory properties of some compounds against MAO activities has been
      markedly differed from their properties as SSAO inhibitors. 2-bromoethylamine has
      been recently developed with a potent, selective and suicide SSAO inhibitor
      without any inhibitory effect on MAO activity Using this inhibitor, it is
      possible to study the role of the enzyme in mammalian tissues. As physiological
      role the increased concentrations of SSAO, especially in blood plasma, have been
      found in diabetic patients and experimental animals. This enzyme was found to be
      associated with translocation of the glucose transporter GLUT 4 into the adipose
      cell surface and involved in the signaling of glucose uptake. Recent studies
      showed that vascular SSAO metabolizes endogenous primary amines, allylamine,
      methylamine and aminoacetone, to the corresponding cytotoxic aldehydes. These
      aldehydes have been linked to the ability of diabetic complications such as
      neuropathy, retinopathy and nephropathy. Overproduction of such toxic aldehydes
      produced by increased SSAO activity was proposed to be potentially hazardous in
      diabetic complications. Thus, reduction or inhibition of SSAO may be beneficial
      in these pathological conditions. Clearly species-related differences in
      properties of SSAO must be taken into account in this respect, particularly when
      assessing if SSAO inhibition may have great application in human.

PMID- 14697908
TI  - Persistency and tolerability of ocular hypotensive agents: population-based
      evidence in the management of glaucoma.

PMID- 14697909
TI  - Patient persistency with topical ocular hypotensive therapy in a managed care
      population.
AB  - PURPOSE: To evaluate persistency with topical ocular hypotensive therapies in
      patients new to pharmacological management of elevated intraocular pressure
      (IOP). DESIGN: Retrospective, cohort study; Protocare Sciences managed care
      database; approximately 3 million members in commercial health maintenance
      organizations and preferred provider organizations and in Medicare risk plans.
      METHODS: Patients were at least 20 years of age initiating therapy between July
      1, 1996, and June 30, 2002, with betaxolol, bimatoprost, brimonidine,
      dorzolamide, latanoprost, timolol, or travoprost as monotherapy. Patients must
      have been continuously enrolled and not have received glaucoma surgery in the 180
      days before the index prescription fill. Prescription refill records for all
      ocular hypotensive drugs were extracted through June 30, 2002. Outcome measures
      were (1) discontinuation of index drug, and (2) either discontinuation or change
      in index drug. Changing therapy was defined as switching to or adding another
      ocular hypotensive. Rates of discontinuation and discontinuation/change were
      compared using Cox regression models. RESULTS: In all, 28,741 patients met the
      inclusion criteria. Compared with latanoprost, those treated with other drugs
      were from 37% (timolol) to 72% (bimatoprost) more likely to discontinue and from
      20% (timolol) to 58% (dorzolamide) more likely to discontinue/change therapy (P
      <.001 for all comparisons). At 12 months, 33% of patients treated with
      latanoprost and 19% of those receiving other ocular hypotensives had not
      discontinued therapy; 23% and 13%, respectively, had not discontinued or changed
      therapy. Compared with latanoprost, significantly higher percentages of patients
      treated with each alternate agent had only one fill of their index drugs (P
      <.001). CONCLUSIONS: Although persistency rates were low across agents,
      latanoprost-treated patients demonstrated significantly greater persistency than
      did those treated with other topical ocular hypotensive therapies.

PMID- 14697910
TI  - Persistency with latanoprost or timolol in primary open-angle glaucoma suspects.
AB  - PURPOSE: To evaluate persistency of pharmacotherapy in primary open-angle
      glaucoma suspects (glaucoma suspects) treated with latanoprost and timolol.
      DESIGN: Retrospective, cohort study using the Protocare Sciences managed care
      database; approximately 3 million members in commercial health maintenance
      organizations and preferred provider organizations and in Medicare risk plans.
      METHODS: Patients 20 years of age or older beginning therapy between January 1,
      1997, and June 30, 2002, with latanoprost or timolol monotherapy were included.
      Patients must have been continuously enrolled and not undergone glaucoma surgery
      in the year preceding the index prescription fill and had glaucoma suspect
      diagnoses before and after the index date. Prescription refill records for all
      ocular hypotensives were extracted through June 30, 2002. The two outcome
      measures were (1) discontinuation of index drug, and (2) either discontinuation
      or change in index drug. Changing therapy was defined as switching to or adding
      another ocular hypotensive. Rates of discontinuation and discontinuation/change
      were compared using Cox regression models. RESULTS: In all, 1,474 patients met
      the inclusion criteria. Latanoprost was prescribed for 583 patients (40%) and
      timolol for 891 (60%). Compared with latanoprost, those treated with timolol were
      39% more likely to discontinue and 27% more likely to discontinue/change therapy
      (P <.001 for both comparisons). At 12 months, 39% of patients receiving
      latanoprost and 25% of those treated with timolol had not discontinued therapy;
      no discontinuation or change in therapy was seen in 30% and 18%, respectively.
      CONCLUSIONS: Latanoprost-treated glaucoma suspects demonstrated significantly
      greater persistency than did patients treated with timolol. The reasons for this
      difference and its impact on intraocular pressure control and disease progression
      require further research.

PMID- 14697911
TI  - Observed time between prescription refills for newer ocular hypotensive agents:
      the effect of bottle size.
AB  - PURPOSE: To describe prescription refill patterns of ocular hypotensive therapies
      and to measure differences among refill rates across bottle sizes. DESIGN:
      Retrospective, population-based, cohort study. METHODS: This study included
      patients dispensed bimatoprost, brimonidine, dorzolamide/timolol, latanoprost,
      timolol gel (XE) 0.5%, or travoprost between January 1, 1996, and March 30, 2002.
      The initial fill date was identified for the cohort-defining ocular hypotensive,
      and the number of days between each subsequent refill was calculated. The
      analysis was repeated in patients with at least four refills to evaluate
      potential bias. Descriptive and survival analyses evaluated differences in refill
      rates across bottle sizes. RESULTS: In the 27,387 patients contributing up to
      four evaluable refill sequences, the amount of drug contained in bottles did not
      predict the number of days between fills. Patients dispensed larger bottles
      typically refilled sooner than drop-count studies would predict; results for
      patients with at least four refills (n = 12,976) confirmed these findings.
      Survival analysis demonstrated that the bottle size trend held across classes of
      therapy. Compared with 5.0-ml bottles, patients dispensed 10.0-ml and 15.0-ml
      bottles returned for refills at approximately 1.5 times the expected rate. When
      average wholesale prices were applied to refill intervals for selected agents, a
      45% excess cost per month was found for the larger bottle sizes (10.0 ml vs 5.0
      ml or 5.0 ml vs 2.5 ml). CONCLUSIONS: Expected refill patterns predicted by
      bottle size and mean number of drops do not reflect observed refill patterns.
      Patients dispensed larger bottle sizes return for refills much sooner than
      expected, regardless of the class of therapy.

PMID- 14697912
TI  - Evidence-based treatment algorithm for mild to moderate Crohn's disease.
AB  - Therapies demonstrated to be effective in randomized, controlled trials for
      induction of remission in patients with mildly to moderately active Crohn's
      disease include sulfasalazine, budesonide, and oral corticosteroids administered
      for 8-16 wk. Patients who relapse within 6-12 months after discontinuation of
      induction therapy should be treated with another cycle of induction therapy and
      then receive maintenance therapy with an immunosuppressive agent (azathioprine, 6
      mercaptopurine, or methotrexate). Long term treatment with budesonide 6-9 mg q.d.
      might be an alternative to immunosuppressive maintenance therapy in patients who
      relapse within 6-12 months after discontinuation and in prednisone-dependent
      patients.

PMID- 14697913
TI  - Maintenance therapy for inflammatory bowel disease.
AB  - Crohn's disease and ulcerative colitis frequently recur after effective induction
      therapy. Accordingly, improved maintenance therapy remains the greatest unmet
      medical need in treating these disorders. Although 5-aminosalicylate compounds
      are widely used to maintain remission in Crohn's disease, the scientific evidence
      supporting this practice is poor. Antimetabolites (azathioprine, 6
      mercaptopurine, and methotrexate) and infliximab are moderately effective in high
      risk patients; however, these drugs might cause significant adverse effects. For
      patients with ulcerative colitis, maintenance therapy with 5-aminosalicylate
      compounds is a mainstay of treatment, being both effective and safe. However,
      this approach is not effective in a minority of patients. Although the purine
      metabolites can be used to treat these patients, strong scientific evidence that
      supports this practice is lacking. An initial experience with probiotic bacteria
      for maintenance of remission in ulcerative colitis seems promising. This article
      reviews the data from randomized, controlled trials of maintenance therapy in
      inflammatory bowel disease.

PMID- 14697914
TI  - Treatment of inflammatory bowel disease: safety and tolerability issues.
AB  - An examination is needed of the potential adverse effects of the agents most
      commonly used to treat inflammatory bowel disease. Most of these therapies can be
      used safely to induce or maintain remissions, although some aspects of monitoring
      for toxicity are necessary. Aminosalicylates, including sulfasalazine and
      mesalamine delivery systems, are most commonly associated with sulfa-related
      effects (sulfasalazine) or intolerance, with rare instances of nephritis,
      pulmonitis, hepatitis, or worsening colitis. The immunomodulators are most
      commonly associated with bone marrow suppression, hepatitis, and the risk of
      opportunistic infections. Methotrexate is contraindicated in pregnancy.
      Antibiotics used for inflammatory bowel disease are generally safe and well
      tolerated, although metronidazole carries a long-term risk of peripheral
      neuropathy. The well-recognized multitude of adverse effects from corticosteroids
      are eliminated or minimized when rapidly metabolized steroids, such as
      budesonide, are used.

PMID- 14697915
TI  - Evaluation of bone mineral density in inflammatory bowel disease: current safety
      focus.
AB  - Crohn's disease and ulcerative colitis constitute a group of disorders
      collectively known as inflammatory bowel disease. Men and women are equally
      affected, and no socioeconomic classes are spared. The age of disease onset is
      relatively young, frequently in the second and third decade of life. The
      constellation of nonspecific symptoms that constitute the prototypic symptoms of
      patients afflicted with inflammatory bowel disease are often overlooked and not
      attributed to their correct origin. These multisystem disorders commonly involve
      the musculoskeletal system. The skeletal system can be involved by the disease
      itself or by the medications used in the treatment of the disease. The finding of
      abnormal bone mineral density in patients with either ulcerative colitis or
      Crohn's disease is a relatively commonplace finding. This review discusses the
      pathophysiology involved in the formation of abnormal bone mineral density and
      the treatment of this condition in patients with inflammatory bowel disease.

PMID- 14697916
TI  - Microscopic colitis: epidemiology and treatment.
AB  - Microscopic colitis, a chronic diarrheal condition, is characterized by colonic
      intraepithelial lymphocytosis, expansion of the lamina propria with acute and
      chronic inflammatory cells, and preserved crypt architecture. These changes, in
      association with a thickened subepithelial collagen band, are termed collagenous
      colitis, whereas changes occurring without a thickened collagen band are
      classified as lymphocytic colitis. Population-based epidemiologic studies confirm
      that microscopic colitis is most frequently diagnosed in middle-aged or elderly
      women and that its incidence is rising. Although these disorders diminish
      patients' quality of life, they are not associated with an increased risk of
      colorectal cancer, and survival is not diminished. Clinical and histologic
      improvement after therapy have been noted in one randomized trial of bismuth
      subsalicylate and three randomized clinical trials of oral delayed-release
      budesonide. A treatment algorithm for microscopic colitis is proposed.

PMID- 14697917
TI  - Cell therapy of renal failure.
AB  - The kidney is unique in that it is the first organ for which long-term ex vivo
      substitutive therapy has been available. The first hemodialyzer was successfully
      applied to a human patient with acute renal failure in 1948, and the first
      successful allograft transplantation was performed with a kidney in 1951. Both
      treatments are used today. There is ample evidence that the small solute
      clearance function provided by hemodialysis does not confer the same survival
      advantage as a functional kidney, both in acute and in chronic renal failure. To
      mimic the metabolic, endocrine, and immunologic functions of the kidney, our
      group has successfully engineered a bioartificial device that includes a
      conventional dialysis filter and a bioreactor containing 10(9) renal proximal
      tubule cells. We have demonstrated differentiated activity of these cells both in
      vitro and ex vivo in a large animal model. The bioreactor has been shown to
      confer a survival advantage in two large animal models of gram-negative sepsis,
      seemingly due to modulation of inflammatory mediators. This bioartificial kidney
      has now completed a Phase I clinical trial in acute renal failure.

PMID- 14697918
TI  - Influence of knowledge and religiousness on attitudes toward organ donation.
AB  - There remains a great need for organ donation. Each year thousands of individuals
      wait for organs to be donated for transplantation. In this study, the Organ
      Donation Attitude Survey (ODAS) was developed. One hundred ninety undergraduate
      students (114 women with a mean age of 20.0 and 76 men with a mean age of 20.5
      years) enrolled in general education classes at a small midwestern university
      participated. The present study determined that ODAS is a reliable and valid
      instrument to assess attitudes regarding organ donation. The data were analyzed
      by stepwise regression to determine which variables were related to attitudes
      regarding organ donation. The results indicated the impact of four variables:
      education regarding organ donation, knowledge of someone who had donated an organ
      after death, awareness of anyone who received a donated organ, and religious
      beliefs. These significant variables in the regression analysis explained 24.95%
      of the ODAS total score variability. The most important results of the present
      study indicated that the ODAS was psychometrically valid and it could be used to
      evaluate attitudes regarding organ donation.

PMID- 14697919
TI  - Results from the organ and tissue transplant program in Nuevo Leon, Mexico, 1996
      to 2001.
AB  - BACKGROUND: Before 1996, solid organs from cadaveric donors (CD) did not account
      for more than 2% of all transplants. The need for more transplants led the state
      to undergo several legislative, societal, organizational, and infrastructure
      changes. OBJECTIVES: A descriptive analysis of the evolution of the transplant
      program in the State of Nuevo Leon, Mexico, from 1996 to 2001. PATIENTS AND
      METHODS: Trimester reports have been routinely performed since 1996 from the 14
      institutions that are licensed to perform organ and tissue transplants in the
      State of Nuevo Leon, Mexico. All reports were concentrated and a descriptive
      analysis is presented herein. RESULTS: From 1996 until 2001, a total of 1457
      organ and tissue (OT) transplants have been performed. At the end of this period,
      there was a 214% increase in the total number of transplants. By 2001, 73% of the
      program's total of 1457 OT transplants came from cadaveric donors. CONCLUSIONS:
      The state transplant program of Nuevo Leon has experienced a dramatic growth
      since 1996. The percent of organs transplanted from cadaveric donors is one of
      the highest in Mexico. There is still much work to be done at the state and
      national levels; better epidemiological studies and dialysis registries are
      needed as well as investment in transplant research.

PMID- 14697920
TI  - 20-year experience with elderly donors in living renal transplantation.
AB  - PURPOSE: This study evaluates the impact of living renal donors (LD) aged 60
      years and older on graft performance and patient survival in an old-for-young
      constellation. PATIENTS AND METHODS: We analyzed 144 consecutive LDs between
      January 1983 and December 2002 (19 patients 60+/125 controls). RESULTS: Mean
      donor age in the 60+ group was 63.7 (+/- 2.6) years and 43.7 (+/- 9.0) years for
      the <60 group. Mean recipient age was 42.4 (+/- 15.2) years versus 32.6 (+/-
      15.3) years HLA-A, -B, and DR-mismatches were 3.16 (+/- 1.3) for the 60+ group
      and 3.13 (+/- 1.7) for the controls (P = NS). Rejection episodes in the first
      year following LD did not differ (53% versus 33%, P =.25). Mean serum creatinine
      for 65+ versus <65 after 1, 3, and 12 months was 1.91 +/- 1.2 versus 1.48 +/-
      0.85 mg/dL (P =.16), 1.82 +/- 0.89 versus 1.29 +/- 0.35 mg/dL (P <.05) and 1.80
      +/- 0.31 versus 1.37 +/- 0.38 mg/dL (P <.05) and mean creatinine clearance at 12
      months 62 versus 82 mL/min (P =.06). Censored 1-, 3-, and 5-year graft survival
      was 100% versus 95% (P = NS), 100% versus 93% (P = NS) and 100% versus 83% (P =
      NS) with no significant difference in the log-rank test for Kaplan Meier.
      CONCLUSION: No impact of donor age was found for graft survival but function of
      the 65+ kidneys at 3 and 12 months was reduced. Living renal donors 60+ are
      acceptable for carefully allocated recipients.

PMID- 14697921
TI  - Renal artery aneurysm in hand-assisted laparoscopic donor nephrectomy: case
      report.
AB  - We report a living donor who underwent laparoscopic nephrectomy using a hand
      assisted device (HALD). At preoperative arteriography the donor showed a renal
      artery aneurysm. The patient was a 37-year-old female, 166 cm height, white,
      weighing 87 kg, HLA identical to the recipient. HALD was indicated due to the
      better visualization of renal pedicle and greater security in an obese patient.
      Renal artery aneurysm is a rare condition, with many possible complications. The
      method proved to be adequate and safe for donor nephrectomy, despite a renal
      artery aneurysm.

PMID- 14697922
TI  - Living donor nephrectomy--no impact of genetic relationship.
AB  - PURPOSE: A retrospective, single-center analysis was conducted to compare the
      results of living donor kidney transplantation between living unrelated (LURD)
      and living related (LRD) donors. PATIENTS AND METHODS: One hundred forty-seven
      consecutive living renal transplantations were performed at our institution,
      starting in 1983. Graft and patient survival were assessed as well as transplant
      function, including a subgroup analysis for the period of kidney transplantation.
      RESULTS: Mean follow up for the LRD group was 88.5 months and for the LURD cohort
      34.4 months. One- and 3-year graft survival (censored for death with functioning
      graft) for LRD versus LURD was 97.5% versus 94.4% (P =.4) and 95.3% versus 88.8%
      (P =.35). Patient survival at 1 and 3 years was 95.1% versus 94.7% (P =.91) and
      87.8% versus 90.0% (P =.79). Of the related recipients, 37% experienced at least
      one episode of rejection in the first year following renal transplantation,
      compared to 34% in the LURD group (P =.80). Mean serum creatinine for LRD versus
      LURD after 1, 3, and 12 months () was 1.52 +/- 0.81 versus 1.59 +/- 1.17 mg/dL (P
      =.98), 1.41 +/- 0.55 versus 1.30 +/- 0.40 mg/dL (P =.51), and 1.44 +/- 0.39
      versus 1.40 +/- 0.40 mg/dL (P =.75). Mean creatinine clearance after 1 year was
      82.2 versus 71.7 mL/min (P =.26). Subgroup analysis for the time between 1996 and
      2002 revealed no difference between LURD and LRD. Multivariate analysis could
      exclude an impact of the significantly different recipient age and of
      first/second warm ischemic time on the endpoints described above. CONCLUSION:
      LURD is a good way to meet the growing organ shortage and should be encouraged.

PMID- 14697923
TI  - One-year posttransplant renal function is a strong predictor of long-term kidney
      function: results from the Neoral-MOST Observational Study.
AB  - BACKGROUND: Peritransplant risk factors influence short-term and long-term graft
      survival, and 1-year serum creatinine is known to predict long-term graft
      survival. To examine interrelationships between risk factors, renal function at 1
      year, and long-term graft function in patients maintained on cyclosporine, we
      analyzed data collected from 10,692 de novo or maintenance renal transplant
      recipients in an ongoing international, prospective, observational study--Neoral
      MOST (Multinational Observational Study in renal Transplantation). The effect of
      donor age, delayed graft function, acute rejection, donor type, panel-reactive
      antibodies, and previous graft on 1- and 5-year renal function and their
      relationship to 1-year serum creatinine was assessed. RESULTS: Donor age, delayed
      graft function, acute rejection, and donor type significantly increased the risk
      for serum creatinine > 130 micromol/L at 1 year posttransplant, and 1-year serum
      creatinine was the strongest predictor of 5-year renal function. After adjustment
      for 1-year serum creatinine, an ongoing influence was observed for donor age,
      donor type, and previous graft. Delayed graft function and acute rejection had a
      significant effect on serum creatinine at year 1 but no additional impact on long
      term graft function. CONCLUSIONS: Serum creatinine at 1 year is influenced by
      risk factors known to affect overall graft survival and is predictive of 5-year
      renal graft function. The effects of delayed graft function and acute rejection
      appear to be limited to their influence on serum creatinine at 1 year, whereas
      donor type and previous graft predominantly affect later stages of graft life.

PMID- 14697924
TI  - Noncompliance after kidney transplantation: a systematic review.
AB  - We performed a systematic review of the literature on medical noncompliance after
      kidney transplantation in the cyclosporine era. We wished to define commonalities
      that may help the clinician identify patients for early intervention. We found
      that patients who were at a higher risk of noncompliance after kidney transplants
      were younger, female, unmarried, and non-Caucasians. Patients who were recipients
      of living donor transplants and had been transplanted for a longer time with a
      history of a previous transplant were also at risk of noncompliance. We also
      found that patients displaying emotional problems, such as anxiety, hostility,
      depression, distress, lack of coping, and avoidant behaviors, were also at risk
      for noncompliance after kidney transplantation.

PMID- 14697925
TI  - Beneficial pharmacokinetic interaction between cyclosporine and itraconazole in
      renal transplant recipients.
AB  - BACKGROUND: Itraconazole is often given for fungal prophylaxis to renal
      transplant recipients, who require concomitant cyclosporine in the immediate
      posttransplant period. We determined the extent of the pharmacokinetic
      interaction between cyclosporine and itraconazole oral solution in renal
      transplant recipients and the effect on daily drug costs. METHOD: This was a
      single-center, open-label, nonrandomized study. Posttransplantation, renal
      transplant recipients received itraconazole solution 200 mg twice daily and
      cyclosporine, dosed to achieve target concentrations. Once at steady state, blood
      samples were collected over 12 hours for pharmacokinetic evaluation of
      cyclosporine, itraconazole, and hydroxy-itraconazole. Itraconazole was
      discontinued after approximately a 3-month prophylaxis regimen. Cyclosporine
      doses were titrated to achieve target concentrations and cyclosporine
      concentrations were once again determined when steady state was achieved. A
      noncompartmental analysis was used to analyze cyclosporine pharmacokinetic
      parameters. The pharmacoeconomic impact was measured based on the percent change
      in dose of cyclosporine when administered with and without itraconazole. Drug
      costs were calculated using the average wholesale price. The cost per patient, as
      well as the average cost, was calculated for the cyclosporine/itraconazole
      combination, as well as the cyclosporine regimen alone. RESULTS: Eight renal
      transplant recipients completed the study. All were included for itraconazole
      analyses and seven for cyclosporine analyses. Mean peak and trough itraconazole
      levels were 1.64 +/- 0.82 and 1.23 +/- 0.90 microg/mL respectively. Mean peak and
      trough hydroxy-itraconazole levels were 2.37 +/- 1.55 and 2.20 +/- 1.48
      microg/mL, respectively. While on itraconazole, a 48% reduction in the mean total
      daily dose of cyclosporine was necessary to maintain target concentrations (171
      +/- 63.6 versus 329 +/- 103.5 mg, P =.003). This reduction in cyclosporine dose
      resulted in a discounted itraconazole daily drug cost of approximately 29.5%.
      CONCLUSION: Administering itraconazole with cyclosporine allows for a decrease in
      the cyclosporine dose, thus lowering daily drug costs and providing adequate
      antifungal coverage with itraconazole and hydroxy-itraconazole trough
      concentrations above the MIC(90) of Candida and Aspergillus spp.

PMID- 14697926
TI  - Triple immunosuppression with or without basiliximab in pediatric renal
      transplantation: acute rejection rates at one year.
AB  - Acute rejection (AR) is a major determinant of chronic allograft dysfunction and
      graft survival. This study evaluated the effect of basiliximab on AR in pediatric
      renal transplantation on triple immunosuppression. Forty-three transplantations
      (25 males and 18 females; mean age 14.9 +/- 3.6 years) were performed between
      1996 and 2002. Thirteen of the grafts came from cadaveric donors and 30 from
      living-related donors. All patients were placed on immunosuppression with
      prednisolone + (azathioprine or mycophenolate mofetil) + (cyclosporine [CYA] or
      tacrolimus). Basiliximab was also administered in 20 cases. The respective rates
      of biopsy-proven AR in the basiliximab group (BG) and the standard-regimen group
      (N-BG) were 0% vs 17.4% (P >.05) at 1 month posttransplantation; 0% vs 26.1% (P
      <.05) at 3 months; 0% vs 26.1% (P <.05) at 6 months, and 7.1% vs 26.1% (P >.05)
      at 12 months. In the N-BG group the 1- and 3-year graft survival rates were 91.3%
      (21/23) and 83.3% (15/18), respectively. The mean glomerular filtration rate
      (GFR) in the first year after the transplantation was 75 +/- 33 mL/min/1.73 m(2)
      in the N-BG and 98 +/- 21 mL/min/1.73 m(2) in the BG patients (P <.05).
      Basiliximab significantly reduced the rates of acute rejection at 3 and 6 months
      after pediatric renal transplantation. The GFR in the first year was
      significantly higher among the patients treated with basiliximab, which was well
      tolerated by all patients and caused no significant adverse effects. The effect
      of basiliximab on long-term graft survival and chronic allograft dysfunction
      deserves further investigation.

PMID- 14697927
TI  - Use of basiliximab with mycophenolate mofetil in kidney transplantation.
AB  - INTRODUCTION: Randomized, placebo-controlled studies have determined that
      administration of basiliximab (chimeric IL-2 receptor antagonist) decreases the
      acute rejection rate in kidney transplantation when used in combination with
      cyclosporine, azathioprine, and steroids. We report our experience using
      basiliximab with mycophenolate mofetil, a calcineurin inhibitor, and steroids in
      kidney transplantation. METHODS: We retrospectively analyzed 127 patients who
      received their first kidney transplant between September 1, 1998, and December
      30, 2000, including 59 who received basiliximab (22 living and 37 cadaveric donor
      recipients) and the 68 that did not receive this antibody (31 living and 37
      cadaveric donor recipients). The groups were demographically comparable for risk
      factors such as race, peak of panel-reactive antibody, delayed graft function,
      donor age, and cold ischemia time. The analysis assessed serum creatinine levels,
      acute rejection, cytomegalovirus infection, and posttransplant
      lymphoproliferative disease incidence as well as patient and graft survival at 6
      months. RESULTS: Serum creatinine levels were 3 +/- 3.1 and 2.6 +/- 2.5 mg/dL (P
      =.346) at discharge, 1.5 +/- 0.6 and 1.7 +/- 1.1 mg/dL (P =.098) at 1 month, and
      1.5 +/- 0.7 and 1.6 +/- 0.7 mg/dL (P =.454) at 6 months posttransplantation for
      patients treated with versus without basiliximab, respectively. Only one episode
      of acute rejection was seen among patients treated with basiliximab within 1
      month posttransplantation versus three episodes among patients treated without
      basiliximab (P =.382). Three patients (5.1%) treated with basiliximab and two
      patients (2.9%) treated without basiliximab developed acute rejection within 6
      months posttransplantation (P =.536). Patient and graft survivals at 6 months
      posttransplantation were not significantly different between patients treated
      with versus without basiliximab (100% and 100% versus 100% and 98.3%,
      respectively). There was no increased incidence of cytomegalovirus infection with
      the use of basiliximab (5.1% vs 5.9%, P =.844). There was only one case of
      posttransplant lymphoproliferative disease within 6 months posttransplantation in
      a patient treated without basiliximab. CONCLUSION: These data suggest that the
      routine addition of basiliximab to a mycophenolate mofetil-based regimens does
      not appear to be warranted. A larger prospective randomized study with longer
      follow-up is needed to confirm these results.

PMID- 14697928
TI  - Influence of 1,25-dihydroxyvitamin D3 as an immunomodulator in renal transplant
      recipients: a retrospective cohort study.
AB  - Many studies suggest that 1,25-dihydroxyvitamin D3 (1,25-[OH](2) D3) and its
      analogues are potent dose-reducing drugs for other immunomodulators, helping to
      prevent graft rejection. In this study, we retrospectively grouped renal
      transplant recipients into two cohorts based on 1,25-[OH](2) D3 use to analyze
      the immunomodulatory effects. Ninety-two subjects were initially enrolled: group
      A (n = 43) recipients who had osteoporosis and were treated with 1,25-[OH](2) D3,
      and group B (n = 49) was a control group. We evaluated the effects on the number
      of acute rejection episodes, the immunosuppressive drug doses, serum calcium
      levels, and overall graft survival. Although before treatment the number of acute
      rejection episodes was statistically higher among group A than group B patients,
      after introduction of 1,25-[OH](2) D3, the difference became nonsignificant. This
      study showed that osteoporotic renal transplant recipients experienced fewer
      acute rejection episodes after 1,25-[OH](2) D3 treatment.

PMID- 14697929
TI  - Recurrent minimal change disease post-allograft renal transplant.
AB  - A young adult was diagnosed with steroid-resistant minimal change disease (MCD)
      without evidence of focal segmental glomerulosclerosis (FSGS) despite serial and
      detailed sectioning and screening of the renal biopsy. He received initial
      treatment with steroids and then cyclosporine plus low-dose steroids for 2 years.
      Renal function progressively deteriorated due to resistance to steroid and
      cyclosporine. Two months after initiation of hemodialysis, the patient received a
      living-related allogenic kidney transplant. However, recurrent nephrotic syndrome
      and renal insufficiency occurred after transplantation. In spite of aggressive
      treatment, renal function showed no significant improvement. The kidney graft was
      removed 2 weeks after transplantation. Serial sectioning and thorough sampling
      and screening revealed no evidence of FSGS, but light microscopy and electron
      microscopy showed the typical morphologic pattern of MCD, corresponding to the
      pretransplant diagnosis. We believe that this is the first reported case of
      recurrent MCD after renal transplant.

PMID- 14697930
TI  - High-grade renal transplant artery stenosis after suboptimal angioplasty:
      favourable long-term outcome.
AB  - The purpose of our report is to present the long-term outcomes of three renal
      transplant recipients with high-grade stenosis and suboptimal percutaneous
      angioplasty (PTA) because of technical difficulties. Two men and one woman of age
      67, 53, and 54 years, who maintained functional cadaveric graft for 17, 9, and 13
      years, and had diagnosed significant renal transplant artery stenosis at 2, 1,
      and 2 years after renal transplantation, respectively, were studied. Stenoses
      were diagnosed angiographically in the first patient and by Doppler in other two
      patients, then confirmed by angiography. All three patients had difficult-to
      treat hypertension with deterioration of graft function in the presence of or
      after introducing ACE-inhibitor therapy. PTA was performed in all patients with
      suboptimal or unsuccessful results as assessed by angiography or control Doppler
      examination--the residual stenosis was significant and practically unchanged.
      Surgery was not performed because of high risk, so patients were further treated
      conservatively. Hypertension was treated avoiding ACE inhibitors. Twelve, 7, and
      7 years after angioplasty the serum creatinine is stable in all patients, even
      decreased compared to pre-PTA and early post-PTA levels, namely, 134, 102, and 75
      micromol/L, respectively. Control Doppler examinations revealed a residual
      stenotic jet in all patients, with slightly decreased peak systolic velocity over
      time, indicating a slightly decreased grade of stenosis. These observations
      suggest that renal transplant artery stenosis, even of high grade, can be stable,
      or even regress with time with excellent long-term graft survival. Randomized
      studies comparing conservative treatment versus revascularization are warranted.

PMID- 14697931
TI  - Long-term predictive value of cyclosporine microemulsion C2 level for chronic
      renal allograft dysfunction.
AB  - This observational study was undertaken in maintenance renal transplant
      recipients to assess the relationship between cyclosporine C(2) and the long-term
      risk of chronic renal allograft dysfunction (CRAD). Pharmacokinetic profiling was
      undertaken twice yearly in 79 patients with stable graft function receiving
      cyclosporine microemulsion (Neoral) and steroids. Mean time since transplantation
      at study entry was 56 +/- 49 months posttransplant. At the end of the
      observational period (mean 43 +/- 14 months) 24 patients (30%) had developed
      CRAD, defined as proteinuria > 500 mg/24 hours associated with a rising serum
      creatinine and confirmed by graft biopsy. There were no significant differences
      at baseline between patients who did vs did not develop CRAD, except for reduced
      incidence of acute rejection in CRAD-free patients. The cyclosporine AUC was
      significantly higher among patients without CRAD (5707 ng. h/mL vs 3994 ng. h/mL,
      P =.0007). Mean C(2) was also significantly higher: 1001 ng/mL in the CRAD-free
      group versus 640 ng/mL in the CRAD group (P =.002). There was no significant
      difference in C(0). Regression analysis showed that the best predictors for the
      occurrence of CRAD were a low AUC (relative risk [RR] 1.54, P <.0001), a low C(2)
      (RR 1.30, P <.0001) and proteinuria (RR 4.95, P <.0001). Probability of freedom
      from CRAD was 90% for C(2) > 900 ng/mL. C(2) appears to be a superior strategy to
      C(0) monitoring of cyclosporine in stable renal transplant patients with regard
      to the risk of CRAD. C(2) values above 900 ng/mL are appropriate to minimize the
      risk of CRAD among patients receiving cyclosporine microemulsion and steroids.

PMID- 14697932
TI  - Testing switchability of a new microemulsion formulation of cyclosporine.
AB  - We assessed the bioavailability of cyclosporine (CyA) in the test formulation
      (Cap Arpimune ME) relative to the reference formulation (Cap Sandimmune Neoral)
      to ascertain the switchability between the two formulations in patients. The
      study population included 30 patients on maintenance hemodialysis awaiting renal
      transplantation. The study adopted a randomized open-label, two-way, two-period,
      two-sequence crossover design. The dose administered was 8 mg/kg/d in two divided
      doses for 5 days in each study period with a washout period of 1 week between the
      two periods. A five-point blood sampling (at 0, 1, 2, 3, and 4 hours postdose)
      was done on the last day of each study period for CyA level monitoring. The study
      measures included C(max) (maximum blood concentration), AUC (area under the blood
      CyA concentration versus time curve, 0 to 4 hours) and actual time concentrations
      at individual sampling times. The differences in mean values for all parameters
      and the least significant differences were less than 20% of reference mean.
      Assessment of bioequivalence using log-transformed data showed that the point
      estimate (ratio test: reference) for C(max) was 0.9717 with a 90% confidence
      interval (CI) of 0.88 to 1.06 and that for AUC was 1.0053 with a 90% CI of 0.90
      to 1.12. The bioequivalence obtained suggests that the test formulation can
      replace the reference formulation in patients who require CyA therapy.

PMID- 14697933
TI  - The expansion of CD4+CD28- T cells in patients with chronic kidney graft
      rejection.
AB  - CD4+CD28- T cells are oligoclonal lymphocytes rarely found in healthy subjects,
      but are present in high frequencies in patients with inflammatory diseases.
      Contrary to paradigm, they are functionally active and produce interferon gamma
      and cytolytic proteins, are cytotoxic in vessels and may contribute to tissue
      damage. The size of the peripheral blood CD4+CD28- T cell compartments was
      determined in 20 healthy individuals, 20 patients after renal transplantation
      with stable graft function, and 20 with chronic graft rejection by two-color FACS
      analysis. In patients with stable graft function, the median frequency of
      CD4+CD28- T cells was 3.1% and was significantly higher in comparison to the
      control group (1.4%) (P <.01). The highest subset CD4+CD28- cells was detected in
      patients with chronic graft rejection (10.65%). The amount of CD4+CD28- cells was
      significantly higher in this group in comparison to patients with stable graft
      function (P <.01). The evaluated number of CD4+CD28- cells in patients after
      renal transplantation, especially in graft recipients with chronic graft
      rejection, suggests a role of these cells in chronic graft destruction.

PMID- 14697934
TI  - Influence of age, sex, and hepatitis C virus infection on peripheral blood
      lymphocyte subsets in stable kidney transplantation.
AB  - BACKGROUND: Young age and hepatitis C virus infection (HCVI) are believed to be
      risk factors in kidney transplantation recipients. The first group is treated
      empirically with an intensive immunosuppressive regimen, because it is considered
      to have high immune alloreactivity. The other cohort usually receives a less
      intensive regimen to avoid excessive immunosuppressive effects. Our aim was to
      investigate the influence of age, sex, and HCVI on immune status in stable kidney
      transplant recipients through measurement of peripheral blood lymphocyte subsets.
      METHODS: Absolute CD3+, CD3+, CD4+, CD3+, CD8+, CD19+, CD16+ CD3- lymphocyte
      counts and CD4/CD8 ratios were assessed at five time points in 65 stable kidney
      allograft patients over 12 months. The subsets were compared according to age,
      sex, and HCVI of the recipients. RESULTS: An inverse association was observed
      between recipient age and absolute CD19+ and CD3+ CD4+ lymphocyte counts, which
      was significant at all time points with respect to CD19+ counts, and at three
      time points with respect to CD3+ CD4+ counts. A significant positive association
      was observed between recipient age and absolute CD3- CD16+ lymphocyte counts at
      three time points. Female recipients showed significantly lower CD3+ CD8+ counts
      and significantly higher CD4/CD8 ratios than male recipients at four time points.
      HCVI recipients showed significantly lower CD16+ CD3- counts at four time points.
      CONCLUSIONS: We observed links between immune status and age, sex and HCVI in
      stable kidney transplant recipients that could offer new insights into
      recommendations for maintenance immunosuppression.

PMID- 14697935
TI  - Frequencies at three polymorphic sites of interleukin-10 gene promoter in
      Brazilian renal recipients.
AB  - We genotyped by PCR-RFLP 141 renal patients (77 men and 64 women with ages
      between 12 and 58, predominantly Caucasians) for allelic variants of three
      polymorphic sites of the interleukin-10 gene promoter, previously showed to be
      associated with different production of IL-10 cytokine: -1082 (G/A), -819 (C/T),
      and -592 (C/A). These polymorphisms may confer flexibility in the common immune
      responses and influence the outcome of allo-responses after transplantation. Our
      aim was to determine the frequencies of three functional polymorphic sites -1082,
      -819, and -592 of the interleukin-10 gene promoter in renal recipients of
      Curitiba, Parana. Parana State is located in southern Brazil, and its capital is
      Curitiba with approximately 1.5 million inhabitants. Genotypes were classified as
      follows: "low" IL-10 producer genotypes (ATA/ATA, ACC/ATA, ACC/ACC),
      "intermediate" genotypes (GCC/ACC, GCC/ATA), and "high" IL-10 producer genotype
      (GCC/GCC). In our population we observed linkage disequilibrium between alleles 
      819C and -592C and this haplotypic combination was more frequent (65%) than -819T
      and -592A. We found significantly reduced frequency of the genotype and haplotype
      responsible for high production of interleukin-10, maybe because we have a
      selected group (only renal patients) or maybe because Brazilian people are very
      heterogeneous (miscegenational), which may differ from other groups.

PMID- 14697936
TI  - Persistent high plasma levels of interleukins 18 and 4 in children with recurrent
      infections of the upper respiratory tract.
AB  - The aim of this study was to examine whether children with recurrent infections
      of the upper respiratory tract might have alterations in the systemic immune
      response to viral infections as compared with healthy control children. We
      quantitated plasma levels of interferon-gamma, interleukin-12, interleukin-18,
      interleukin-4, lymphocyte subpopulations, serum immunoglobulins, and subclasses
      of immunoglobulin G in 30 children under the age of 6 years with recurrent
      infections of the upper respiratory tract, both during the acute phase of the
      infection and 4 weeks later, when clinical symptoms had resolved, as well as in
      20 normal controls. We found elevated levels of immunoglobulin G primarily due to
      increased levels of immunoglobulin G(1). Moreover, significantly higher levels of
      interleukin-18 and interleukin-4 were noted during the acute phase of infection
      among children with an increased incidence of respiratory infections as compared
      with the controls (P =.022 and P =.0001, respectively), while plasma levels of
      interferon-gamma and interleukin-12 were significantly lower (P =.034 and P
      =.0001, respectively) than in controls. We suggest that an imbalance between T
      cell helper type-1 and T-cell helper type-2 immune responses might be responsible
      for the perpetuation of recurrent infections of the upper respiratory tract.

PMID- 14697937
TI  - Development of diabetes mellitus post-renal transplantation is associated with
      poor short-term clinical outcomes.
AB  - BACKGROUND: Although posttransplant diabetes mellitus (PTDM) is associated with
      poor long-term outcomes short-term outcomes are not well studied in renal
      transplant recipients (RTRs). METHODS: RTRs between January 1999 and December
      2000 (n = 181) stratified according to the occurrence of diabetes mellitus (DM),
      namely, non-DM (n = 72), previous DM (n = 88), and PTDM (n = 21) were compared
      for infections, hospital readmissions, and graft rejections during the first 6
      months posttransplantation. RESULTS: PTDM showed patients affected by a
      significantly higher rate of infections (57.1% vs 29.2%) and recurrent infections
      (28.5% vs 11.1%) compared to non-DM and a trend toward an increase compared to
      previous DM. PTDM patients had a significantly higher incidence of multiple
      readmissions compared to both previous DM (52.4% vs 20.5%) and non-DM (52.4% vs
      23.6%). Subjects with PTDM showed a significantly higher occurrence of rejection
      (28.6% vs 9.1%) and recurrent rejection (14.3% vs 2.3%) than previous DM and a
      greater trend compared to non-DM. CONCLUSION: PTDM is associated with poorer
      short-term outcomes than either non-DM or previous DM.

PMID- 14697938
TI  - De novo diabetic nephropathy on renal allografts.
AB  - BACKGROUND: Posttransplant diabetes mellitus (PTDM) is a well-recognized clinical
      problem following renal transplantation. Long-term risks of PTDM are similar to
      those of diabetes mellitus in general population. The aim of our study was to
      identify de novo diabetic nephropathy (DN) in our group of patients with PTDM.
      METHODS: Thirty-four patients with PTDM were reviewed retrospectively. Light
      microscopy, immunofluorescence, and electron microscopy techniques were performed
      in 10 of 21 patients with graft biopsy. RESULTS: Five patients (four women, one
      man), aged 47.4 years (range, 29 to 58), four of whom received cadaveric grafts,
      were found to have de novo DN. Their serum creatinine was 211.4 micromol/L
      (range, 140 to 294). Three patients were slightly proteinuric (0.3 to 0.5 g/L).
      PTDM was diagnosed 2.4 months after transplantation (range, 1 to 6). Histologic
      diagnosis of de novo DN was made, on average, 52.6 months after transplantation
      (range, 8 to 115), and 50.2 months (range, 2 to 114) after PTDM. De novo DN
      presented as diffuse diabetic glomerulosclerosis in four patients and nodular
      diabetic sclerosis in one patient, and combined with transplant glomerulopathy in
      all five patients. The mean graft survival time for this group of patients was
      equivalent with a control group. Although the difference in slopes of serum
      creatinine between the studied groups was clinically relevant, it was not
      statistically significant. CONCLUSION: In view of our findings, when histologic
      de novo DN was found in 5 out of 10 patients, one could conclude that de novo DN
      could be a frequent complication of PTDM.

PMID- 14697939
TI  - Obesity as an independent predictor of posttransplant diabetes mellitus.
AB  - BACKGROUND: In the general population, there is a clear association between
      obesity and type 2 diabetes mellitus. However, the evidence of relationship
      between body mass index (BMI: weight/height(2)) and the risk of posttransplant
      diabetes mellitus (PTDM) is inconsistent when studied at a level of single
      center. The aim of our study was to determine if pretransplant BMI is an
      independent risk factor for PTDM at our center and to demonstrate the pattern of
      weight gain in patients who develop PTDM. METHODS: This is a retrospective
      analysis of renal allograft recipients at University of Colorado Hospital. The
      medical records of patients who received a kidney transplant from January 1998 to
      March 2001 were screened to identify the cases of PTDM. Controls were matched for
      immunosuppressive regimen, gender, and type of donor. A total of 18 cases and 36
      controls were identified. RESULTS: The incidence of PTDM in our transplant
      population was 10%. Of these cases, 72% developed PTDM in the first 2 months
      after transplant, and 38% of them required insulin. On multivariate analysis, BMI
      was significantly associated with PTDM (adjusted odds ratio 1.22, 95% confidence
      interval 1.04-1.42) while controlling for number of rejections, age, and other
      factors. We also noticed that weight gain was significantly lower in patients who
      developed PTDM after transplantation. CONCLUSIONS: We conclude that obesity is an
      independent predictor of PTDM. The weight gain was significantly poor among
      patients who developed PTDM. Among all the risk factors for PTDM, obesity is the
      only modifiable risk factor before transplantation. Obese patients should be
      treated with a less diabetogenic immunosuppressive regimen and be counseled to
      lose weight before transplant.

PMID- 14697940
TI  - Gastric emptying time in renal transplant recipients treated with cyclosporine.
AB  - Gastric emptying time (GET) appears to be a rate-limiting factor in the
      absorption of cyclosporine-A (CsA) and may be responsible for intra- and
      interpatient variability of CsA bioavailability. Few studies have assessed
      gastric motility after renal transplantation. The purpose of this study was to
      evaluate gastric emptying of semi-solid material in stable renal transplant
      patients with reference to blood CsA levels. The GET of semi-solids (GET t(1/2),
      half emptying time) was measured in 16 transplant recipients who were taking CsA
      (Neoral), prednisolone and azathioprine (or mycophenolate mofetil). The GET
      (t(1/2)) measured by radionuclide methods, was analyzed with reference to the
      daily CsA doses, levels of CsA (C(0)), and serum creatinine concentrations. The
      mean GET (t(1/2)) was 89.1 +/- 26.4 minutes. Twelve patients exhibited delayed
      gastric emptying with a mean CsA level of 171.8 +/- 56 ng/mL and a mean dose of
      4.1 +/- 1.1 mg/kg/d. The GET (t(1/2)) was not significantly correlated with the
      serum creatinine levels, the time since transplantation, or the CsA
      concentration. In addition, the correlation between the mean daily CsA dose and
      the GET (t(1/2)) was only weakly positive, (r =.33, P =.2) and therefore,
      statistically insignificant. In conclusion, it could not be ascertained whether a
      higher dose of CsA delays gastric emptying or whether patients with delayed
      emptying require higher doses of CsA. However, it is believed that determining
      the GET after transplantation helps in the adjustment of immunosuppressant doses.

PMID- 14697941
TI  - Plasma tissue-type plasminogen activator, fibrinogen, and time on dialysis prior
      to transplantation are related to carotid intima media thickness in renal
      transplant recipients.
AB  - The majority of deaths among patients after renal transplantation is attributed
      to cardiovascular disease (CVD). Intima media thickness (IMT) of the common
      carotid artery is related to coronary and cerebrovascular arterial disease. One
      of the major causes of death due to CVD is acute coronary syndrome, which is
      precipitated by coronary plaque rupture and subsequent thrombosis. The aim of the
      study was to evaluate associations between some fibrinolytic factors: antigens of
      tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI
      1), and thrombin-activatable fibrinolysis inhibitor (TAFI), and IMT in a
      population of renal transplant recipients. The study was performed on 33
      Caucasian, clinically stable kidney transplant recipients (11 women, mean age 43
      years, range 26 to 62 years). All the patients were on triple immunosuppressive
      regimen (cyclosporine, prednisone, and azathioprine) and had stable graft
      function (serum creatinine 1.7 +/- 0.7 mg/dL). The mean time since
      transplantation was 49.9 months (range 4.1 to 131.8 months). In univariate
      analysis IMT correlated significantly with age (r =.5; P =.001), pulse pressure
      (PP) (r =.4; P =.05), time on dialysis prior to transplantation (r =.6; P =.001),
      fibrinogen (r =.4; P =.02), and t-PA (r =.6; P =.001). Multiple regression
      analysis showed that t-PA antigen concentration (P =.001), fibrinogen (P <.05),
      and time on dialysis prior to transplantation (P <.05) were positive independent
      predictors of IMT. These data support the concept of the coincidence of
      disturbances in fibrinolysis and arterial remodelling in patients after kidney
      transplantation. On the other hand the study shows that the duration of dialysis
      therapy before transplantation is detrimental to the arterial vasculature.

PMID- 14697942
TI  - West Nile meningo-encephalitis infection in a kidney transplant recipient.
AB  - West Nile virus is an arbovirus known to cause meningo-encephalitis in immuno
      competent as well as in immunocompromised patients. Herein, we describe a kidney
      transplant recipient in whom meningo-encephalitis infection was caused by the
      West Nile virus. The clinical presentation was fever, headache, photophobia,
      confusion, neck stiffness, and positive Kerning test. The patient was treated
      with IV acyclovir, cefuroxime, ampicillin, and fluids. During hospital stay, the
      patient did not experience any episode of allograft rejection. Fever resolved and
      at follow up he was doing well. West Nile virus infection should be considered in
      immunocompromised patients including transplant recipients with meningo
      encephalitis, especially during epidemic outbreaks.

PMID- 14697943
TI  - Reflex sympathetic dystrophy syndrome in renal transplanted patients under
      immunosuppression with tacrolimus.
AB  - Reflex sympathetic dystrophy syndrome (RSDS), which probably has a multifactorial
      etiology, may appear after kidney transplantation. Its clinical manifestations
      include severe periarticular pain with inflammatory signs, especially in knees
      and ankles, causing functional disability. Symptoms develop during the first 3
      months after transplantation and usually disappear 3 to 6 months later without
      sequelae. In renal transplant recipients it has previously been related to
      immunosuppressive treatment with cyclosporine. Therefore we had suggested that
      introducing tacrolimus could be a therapeutic option. We now present four cases
      of RSDS in kidney transplant recipients treated with tacrolimus. All but one
      patient were receiving tacrolimus monotherapy, excluding other drugs that might
      have been involved to cause the syndrome. It is also interesting that one of our
      cases develop RSDS long after transplantation when immunosuppressive treatment
      was changed. Symptoms correlated with an increase in alkaline phosphatase and
      with bone scintigraphy findings. All patients recovered without sequels 3 to 6
      months afterward. In conclusion, RSDS is a relevant osteoarticular complication
      in patients receiving either anticalcineurinic drug (CyA or tacrolimus), even
      under monotherapy or with a low steroid dose.

PMID- 14697944
TI  - Some aspects of hemostasis in kidney transplant recipients maintained on
      cyclosporine, azathioprine, and prednisone in comparison to patients treated with
      cyclosporine and prednisone.
AB  - Cyclosporine (CyA) has been implicated to increase cardiovascular morbidity and
      mortality after renal transplantation. Impairment of the fibrinolytic system is
      one factor involved in the development of thrombotic complications. The aim of
      this study was to compare hematological and hemostatic parameters among patients
      on CyA, azathioprine, and prednisone (n = 31) versus CyA and steroids (n = 14).
      Using commercially available kits we evaluated thrombin activity as thrombin
      antithrombin complexes (TAT), prothrombin fragments (1 + 2), thrombin activatable
      fibrinolysis inhibitor-(TAFI), TAFI activator, thrombomodulin (TM)-a marker for
      endothelial cell injury,-plasmin generation (plasmin-antiplasmin complex PAP), a
      glycoprotein linking coagulation and fibrinolysis. We observed that patients not
      treated with azathioprine displayed longer prothrombin times and activated
      partial thromboplastin times; higher fibrinogen, platelet counts and fibrinolytic
      activity index (FAI); shorter euglobulin clot lysis time; as well as lower
      thrombin generation markers namely, prothrombin fragments 1 + 2 and thrombin
      antithrombin complexes. Although patients in the non-AZA group tended to have
      been engrafted for a longer time (P =.086), the groups did not differ with regard
      to age, BMI, erythrocyte count, hematocrit, leukocyte count, creatinine
      clearance, alanine and asparagine aminotransferase activities mean arterial blood
      pressure, fibrinogen, TAFI, thrombomodulin, or plasmin-antiplasmin complexes.
      These findings suggest that kidney transplant recipients on triple therapy are at
      greater risk of cardiovascular disease than those without azathioprine treatment,
      despite the lower fibrinolytic activity.

PMID- 14697945
TI  - Xanthogranulomatous pyelonephritis in nonfunctioning transplanted kidney.
AB  - Xanthogranulomatous pyelonephritis in native and allografted kidneys is a rare
      variant of severe chronic infection of the renal parenchyma. In a native kidney
      the diagnosis may sometimes be established by ultrasonography and computed
      tomography. In the renal allograft, the diagnosis could only be established by
      histologic evaluation of the transplant biopsy or nephrectomy. The reported case
      presents a febrile patient with a failing renal graft, in whom
      xanthogranulomatous pyelonephritis was established by histologic evaluation of
      transplantectomy specimens. Xanthogranulomatous pyelonephritis should therefore
      be included in the list of possible etiologies of the fever in patient with
      nonfunctioning transplanted kidney.

PMID- 14697946
TI  - Thyroid function and morphology in kidney transplant recipients, hemodialyzed,
      and peritoneally dialyzed patients.
AB  - Disturbances in thyroid function are common among patients on renal replacement
      therapy. The aim of the present study was to compare thyroid stimulating hormone
      (TSH) and thyroid morphology among patients on hemodialysis (HD), peritoneal
      dialysis (CAPD), and after kidney transplantation. The study was performed on
      three groups of patients: 48 transplant recipients (Tx) (receiving cyclosporine,
      azathioprine, and prednisone); 32 HD, and 26 CAPD patients. The control group
      included 40 healthy volunteers. Thyroid examinations were performed with a 7.5
      MHz probe and the thyroid volume was calculated. Among Tx patients the thyroid
      volume was 25.16 +/- 12.27mL; 21.60 +/- 10.33mL in HD; 19.70 +/- 8.46 mL in CAPD;
      and 16.34 +/- 5.46mL in the healthy volunteers. Serum TSH was within the normal
      range in each group. Goiter was diagnosed in the majority of Tx, most HD
      patients, and some CAPD patients. Single and multiple nodules were found in 21
      Tx, 12 HD, and 2 CAPD patients. Moreover, parathyroid glands were visualized on
      sonography in 10 Tx, 12 HD, and 8 CAPD subjects. In Tx observed correlations were
      positive between thyroid volume and creatinine, negative between thyroid volume
      and TSH. The time after transplantation correlated negatively with TSH. No
      correlation between TSH, thyroid volume, and time on dialysis was observed. The
      prevalence in patients on renal replacement therapy was higher than that in the
      general population. These findings suggest that screening for abnormal thyroid
      morphology should be performed in kidney patients and that iodide supplementation
      should be considered in Tx patients.

PMID- 14697947
TI  - Human cytomegalovirus-associated periodontitis in renal transplant patients.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) infection is associated with renal
      transplant failure. Periodontal pockets may be reservoirs for HCMV replication.
      OBJECTIVES: This study was done to determine active HCMV replication in saliva
      and gingival crevicular fluid of renal transplant patients affected by
      periodontitis. METHODS: HCMV pp67-mRNA amplification was analyzed in oral fluids
      of 38 transplant recipients at 6 months' posttransplantation. Patients received
      antiviral therapy until 3 months' posttransplantation. The HCMV-positive cell
      line VR-977 was the positive control, and oral fluids from healthy volunteers
      served as the negative control. Periodontitis was diagnosed by clinical
      examination. Serum HCMV IgG and IgM were analyzed to differentiate recent and
      latent infection. RESULTS: Prevalence of gingival overgrowth was 68.4%. HCMV gene
      transcripts were detected in the saliva of 21% and the gingival crevicular fluid
      of 18% of patients. All patients (100%) with HCMV pp67-mRNA detected in saliva
      demonstrated clinical manifestations of viral infection, as did 86% of patients
      with HCMV pp67-mRNA detected in the gingival crevicular fluid. Serum IgM was
      positive in 7.9% of patients and IgG in 65.8%; however, associations with active
      mRNA replication were not statistically significant. CONCLUSIONS: Renal
      transplant patients affected by periodontitis are at risk of viral replication
      within the periodontal tissues despite antiviral therapy. This study suggests
      that use of HCMV pp67-mRNA detection in saliva and gingival crevicular fluid
      provides markers of active viral infection, and evidence for a link between HCMV
      associated periodontitis and renal transplant complications.

PMID- 14697948
TI  - Surgery for aortoiliac aneurysm after kidney transplant.
AB  - OBJECTIVE: Although aortoiliac aneurysm in kidney transplant patients is
      uncommon, aortic clamping during the surgical repair of an aneurysm could pose a
      risk to the grafted kidney and might also increase the risk of vascular
      prosthesis infection due to immunosuppression. Herein, we present our results
      related to the treatment of the aortoiliac aneurysm subsequent to kidney
      transplant. MATERIAL AND METHODS: Four male kidney transplant recipients
      underwent surgery for aortoiliac aneurysm repair. RESULTS: In the first patient,
      we protected the kidney graft by perfusion with cold physiological saline. No
      such protective measures were taken in the remaining three patients other than
      reducing warm ischemia to a minimum. In one patient with occlusive disease and
      impaired graft function, renal function improved after surgery. In the other
      three patients renal function was unaffected by surgery. Despite
      immunosuppression, no infection of the prostheses was observed. CONCLUSIONS:
      Surgery for aortoiliac aneurysm can be safely performed in kidney transplant
      patients. No ischemic damage is incurred by the graft and perioperative infection
      can be easily avoided. The need to protect the graft during the surgical
      procedure should be evaluated in each individual case according to predicted
      times of ischemia and vascular reconstruction and preoperative graft function.

PMID- 14697949
TI  - Quality of life of living donors before and after living donor liver
      transplantation.
AB  - Living donor liver transplantation (LDLT) is becoming an established method for
      treatment of terminal liver disease in adults. After resection of the right
      hepatic lobe, postoperative complications can arise in healthy donors, and even
      individual cases of death have been recorded. There remains, however, little
      research on the psychosocial aspects in living donors before and after LDLT.
      Using the WHOQOL questionnaire, this prospective study investigates the quality
      of life (QoL) in a sample of 28 living donors, including the relationship between
      postoperative complications and QoL before and 6 months after donation. Before
      LDLT, the donor QoL is high, above that of the general healthy population. After
      LDLT, a significant reduction in the QoL appears in the areas of "physical
      health" and "living conditions." Nevertheless, the QoL remains above the level of
      the general population. Only two donors showed general QoL values below those of
      the general population. The postoperative complications had no significant
      influence on the QoL after transplantation. The high QoL of donors following LDLT
      indicates a positive psychosocial outcome for the majority of donors,
      irrespective of donation-related complications. Additional psychosocial studies
      will be necessary to disclose predictors for an unfavorable psychosocial outcome
      following LDLT.

PMID- 14697950
TI  - Preservation injury patterns in liver transplantation associated with poor
      prognosis.
AB  - Preservation injury (PI) is defined as hepatic dysfunction that occurs within 10
      days of liver transplantation (OLT) but spontaneously resolves. However, we noted
      two new patterns: one characterized by histologic evidence of preservation injury
      that occurs at later than 10 days post-OLT (late PI), and a second, of persistent
      charge in liver biopsies > 10 days post-OLT (persistent PI). To characterize
      these new patterns, we performed a retrospective study of patients who underwent
      liver biopsies for hepatic dysfunction post-OLT from September 1993 to March
      1998. The outcome of the 61 patients with preservation injury on liver biopsy
      after OLT was followed until the last clinic visit or death. Thirty patients had
      early PI, 16 patients had persistent preservation injury and 15 patients, late
      onset preservation injury. There were no significant differences in the age (P
      =.28), sex (P =.77), follow-up time (P =.78), cold ischemia (P =.3), or warm
      ischemia time (P =.16) between these groups. There was also no significant
      association between early preservation injury or persistent preservation injury
      with the development of acute or chronic rejection (P =.19). The overall survival
      rates at 1, 3, and 5 years was 52%, 45%, and 45%, respectively. There was no
      significant difference in survival between early, persistent, and late PI
      patterns (P =.59), although there was a trend toward better survival for patients
      with early preservation injury. The survival of OLT patients with persistent or
      late preservation injury is poor and should prompt consideration for
      retransplantation.

PMID- 14697951
TI  - Serum matrix metalloproteinase MMP-2 and MMP-9 in the late phase of ischemia and
      reperfusion injury in human orthotopic liver transplantation.
AB  - INTRODUCTION: Ischemia and reperfusion (I/R) injury during orthotopic liver
      transplantation (OLT) is accompanied by neutrophil infiltration and degradation
      of extracellular matrix. Matrix metalloproteinases (MMP) play an important role
      in the turnover of extracellular matrix components. We assessed the changes in
      level and composition of serum MMP-2 and MMP-9 in relation with I/R injury after
      human OLT. METHODS: Thirty-three patients were separated into two groups
      according to their peak level of aspartate aminotransferase (AST) after OLT (AST
      < 1500 IU/L: n = 22; AST > 1500 IU/L: n = 11). Serum MMP-2 and MMP-9 were
      measured before transplantation as well as 2 days and 1 week after OLT using
      ELISA (MMP protein) and BIA (enzymatic activity of MMP). RESULTS: MMP-2 and MMP-9
      protein concentrations were comparable before and 2 days after OLT, whereas at 1
      week MMP-2 decreased and MMP-9 increased significantly. However, there were no
      significant differences between patients with high or low peak AST at all time
      points. Also, the composition of MMP-2 and MMP-9 did not differ over time between
      the groups of patients. CONCLUSION: Serum MMP-2 and MMP-9 do not relate to the
      late phase of hepatic I/R injury after human OLT.

PMID- 14697952
TI  - Anesthetic management and complications in living donor hepatectomy.
AB  - A total of 112 living donor hepatectomies (LDHs) performed from October 1999 to
      April 2003 at Ege University Hospital Organ Transplantation Center were reviewed
      and perioperative anesthetic courses and complications were determined. There was
      no perioperative mortality. Mean duration of operations was 333 +/- 77 minutes
      (range, 160 to 540 minutes) for right lobectomies and 277 +/- 88 minutes (range,
      150 to 500 minutes) for left lateral segment plus left lobe operations. The
      remnant liver volume ratios of the patients was 0.58 +/- 0.16 (range, 0.30 to
      0.91) after harvesting. Crystalloids, colloid infusions, and transfusions aimed
      to keep hematocrit >25%, central venous pressure (CVP) <5 mm Hg and to maintain a
      urine output >1 mL/kg(-1) while nitroglycerin was infused (0.5 to 2.0 microg/kg(
      1)h(-1)) when needed to allow fluid infusions freely without increasing the CVP
      values. No transfusion was needed for 91 patients (81%) and 21 right lobectomy
      patients needed transfusion of blood products. Initial mean hematocrit of 38.9 +/
      4.9% (range, 27% to 50%) for all patients was found 31.5% +/- 5% (21% to 44%) at
      the end of the operation. Albumin blood levels averaged 4.27 +/- 0.49 g/dL(-1) at
      the beginning and 3.28 +/- 0.45 g/dL(-1) after hepatic resection. Perioperative
      complications were one air embolism, postoperative systemic inflammatory response
      syndrome in one patient, transient but severe hemoglobinuria due to a predonated
      autologous blood transfusion in another, prolonged recovery for neuromuscular
      blocker overdose in one patient, and postoperative atelectasis in three patients,
      two of whom had pneumonia later while two other patients had pleural effusions.
      One required a drainage. Living donor hepatectomies were performed with
      acceptable complications in anesthetic management during this study. The
      operation provides us with an optimal liver segment without resulting in
      mortality.

PMID- 14697953
TI  - Orthotopic liver transplantation from a donor with a history of schistosomiasis.
AB  - The shortage of liver donors and the increasing number of patients on the waiting
      list for liver transplantation have led to a widening of the definition of
      suitable liver donors. In this case report, we describe transplantation of a
      liver from a 20-year-old brain-dead donor with a past history of schistosomiasis.
      Careful evaluation for schistosomiasis-related hepatic complications using
      hepatic function tests, clinical assessment for manifestations of portal
      hypertension, as well as abdominal ultrasound, and liver biopsy were performed.
      At 7 months follow-up, the recipient is doing well with normal liver function.
      Liver transplantation from a donor with a history of schistosomiasis is
      acceptable in carefully screened cases.

PMID- 14697954
TI  - Outcomes of liver transplantation for cryptogenic cirrhosis: a single-center
      study of 71 patients.
AB  - Cryptogenic cirrhosis (CC) is emerging as an important indication for orthotoptic
      liver transplantation (OLT) in the United States. Our aim was to identify risk
      factors associated with nonalcoholic steatohepatitis (NASH) in patients with CC
      and to evaluate outcomes following OLT. PATIENTS AND METHODS: A chart review was
      performed on patients transplanted for CC at the University of Nebraska Medical
      Center between October 1993 and May 2003. RESULTS: Seventy-one patients were
      identified (37 were men and 34 women). Average age was 53.5 years. Mean
      cholesterol and triglyceride levels increased from 174.8 to 222.3 mg/dL (P <.05)
      and from 162.60 to 279.66 mg/dL (P <.05), respectively. The prevalence of
      diabetes mellitus also increased from 37.14% to 54.93% (P <.05). Incidental
      hepatocellular carcinoma was present in six patients and high-grade dysplasia in
      one patient. Steatohepatitis developed in eight patients and recurrent
      cryptogenic disease in four, of whom one required retransplantation for
      decompensated liver disease. Rejection occurred in 24 patients. Cumulative
      incidence of graft failure at 1 year was 4% (95% CI 0% to 10%) and at 5 years was
      7% (95% CI 0% to 18%). Survival at 1 year was 85% (95% CI 77% to 94%) and at 5
      years was 73% (95% CI between 61% to 86%). CONCLUSIONS: Cryptogenic liver disease
      is an important cause of decompensated cirrhosis; NASH appears to be an
      intermediate stage in the development of this disease in a subset of patients.
      Short-term and 5-year survival rates in this series appear comparable to other
      liver transplant recipients, supporting liver transplantation as an acceptable
      treatment for CC.

PMID- 14697955
TI  - Duct-to-duct biliary reconstruction for living donor liver transplantation:
      experience of 92 cases.
AB  - Bile duct-to duct reconstruction is now performed in living donor liver
      transplantation (LDLT) for adult patients. To confirm the feasibility, the
      results after the reconstruction were retrospectively analyzed. The subjects were
      92 adult patients who underwent LDLT at the University of Tokyo Hospital. During
      the observation period (median 546 days), biliary complications were observed in
      28 cases (30%). The complications included bile juice leakage in 11, stenosis at
      the anastomotic site in 9, and tube trouble in 8. Of these, 20 patients required
      surgical revision. The results suggest that duct-to-duct reconstruction provides
      satisfactory results, although long-term observation will be necessary.

PMID- 14697956
TI  - Liver transplantation for the management of hepatoblastoma.
AB  - INTRODUCTION: Hepatoblastoma (HEP) is the most frequent liver malignancy
      occurring in childhood. Surgical resection currently represents the gold standard
      for treatment. In patients with initially unresectable tumors, chemotherapy may
      induce remarkable reductions in size. In nonresponder patients, liver
      transplantation (OLTx) may offer a chance of cure. MATERIALS AND METHODS: From
      1990 to 2003, a total of 400 OLTx (31 pediatric transplants) have been performed
      at Padua University. Seven patients (4 males and 3 females) underwent OLTx for
      hepatoblastoma. All patients presented with bilobar liver involvement and had
      received chemotherapy according to the SIOPEL-1. In all patients preoperative
      staging was negative for extrahepatic involvement. RESULTS: The mean age of the
      pts was 8.2 years (range 6.4 months to 34 years). Mean follow-up after OLTx was
      41.4 months (median 36, range 3 to 108 months). Actuarial patient survival rates
      after OLTx for hepatoblastoma are 83.3%, 83.3%, and 56% at 1, 3, and 5 years,
      respectively. Five of seven subjects with HEP are alive after transplant at 3,
      12, 36, 65, and 108 months. Two patients died owing to recurrent disease after 6
      and 60 months, respectively, from transplantation. Another subject, primarily
      treated with surgical resection, shows HEP recurrence at 40 months after OLTx.
      The remaining 4 patients are alive and well at a mean follow-up of 28 months
      (median 24, range 3 to 65 months). CONCLUSIONS: Liver transplantation may
      represent a valid therapeutic option for patients with unresectable HEP, but it
      is contraindicated in cases of recurrence following previous resection surgery.
      Neo-adjuvant chemotherapy is of paramount importance to obtain good long-term
      results.

PMID- 14697957
TI  - Hepatocellular carcinoma in liver transplant era: a clinicopathologic analysis.
AB  - Hepatocellular carcinoma (HCC) is one of the most common tumors in the world, and
      the prognosis is usually poor. Today, liver transplantation (LT) is a radical but
      frequently curative treatment modality for HCC. In selected patients, it cures
      HCC and the underlying cirrhosis at the same time. The present
      clinicopathological study examined the importance of tumor characteristics for
      their effects on recurrence and survival rates after LT for HCC. Forty-two native
      hepatectomy specimens among 250 consecutive orthotopic liver transplantations
      contained HCC. Patients were predominantly men (30 men, 12 women), ranging in age
      from 1 to 61 years (median 51). While 20 patients received cadaveric organs, 22
      were transplanted from living donors. In 14 patients (33%) HCC presented as a
      solitary nodule, 5 (12%) as two nodules; 2 (5%) as three nodules; and 21 patients
      (50%) as more than three nodules. The maximal diameter of the largest tumor not
      larger than 3 cm in 28 patients (66%), exceeding this size in 14 patients (34%).
      There was a significant correlation between nodule number and tumor size (r =
      0.36, P = 0.05). While 23 patients had no sign of vascular involvement, 17 tumors
      showed microscopic invasion and two large vessel involvement. There was a
      positive correlation between vascular invasion and nodule number (r = 0.41, P =
      0.05). The histopathological grade of differentiation of the tumors was assessed
      as "well" in seven patients (14%), moderate in 28 (72%), and poor in 7 (14%). The
      differentiation was significantly poorer when vascular invasion was observed (r =
      0.43, P =.01). According to the TNM classification, 11 patients (26%) were stage
      I, 6 (14%) stage II, 13 (31%) stage III, and 12 (29%) stage IV. After a median
      follow-up of 10 months (1-50 months), the overall mortality was 18% (n = 8).
      Patient survival at 6 month, 1, and 4 years was 88%, 80%, and 60%, respectively.
      The outcome was significantly poorer for TNM stage IV versus stage I,II, and III
      tumors to (P =.02). Tumor recurred in three patients at 4,6, and 50 months after
      liver transplantation. The sites of recurrence were bone, lung, and adrenal
      glands. In conclusion, liver transplantation represents a safe and feasible
      treatment for hepatocellular carcinoma with excellent outcomes compared with
      other treatment modalities. Liver transplantation offers excellent survival rates
      and chance for cure in stages I, II, and III hepatocellular carcinoma in
      cirrhotic patients.

PMID- 14697958
TI  - Adjuvant chemotherapy for transplanted hepatocellular carcinoma patients: impact
      on survival or HCV recurrence timing.
AB  - INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common tumors
      worldwide. In the Western world the current epidemic of cirrhosis due to the
      hepatitis C virus (HCV) is increasing the number of new cases. Liver
      transplantation (OLTx) represents a radical treatment for HCC and the underlying
      cirrhosis. Whether adjuvant chemotherapy is indicated in the postoperative period
      to prevent recurrence is controversial. MATERIAL AND PATIENTS: Forty-eight HCC
      patients underwent liver transplantation during 11 years, including 21 who were
      chemo-treated (CT) patients. Thirty-one patients (65%) had post-necrotic virus-C
      cirrhosis (PNC-C). Twenty-one cases (44%) were p-TNM stages III-IV, and 15 cases
      (31%) incidental HCC detected in the explanted liver. Seven HCV patients (15%)
      received chemotherapy (before 1998). RESULTS: One-, 3-, and 5-year overall
      survival rates were 100%, 85%, 79% (CT group), and 89%, 71%, 71% (no CT group),
      respectively. The HCV recurrence-free survival rates at 3, 6, and 12 months were
      29%, 14%, 0% for the CT group, versus 76%, 38%, 25% for the no CT group (P
      =.005). CONCLUSIONS: Discontinuation of HCV-HCC patients by chemotherapeutic
      adjuvant protocols after transplantation appears rational due to the early
      hepatitis C recurrence confirmed in our series. Moreover, few studies have
      demonstrated that CT prolongs survival of HCC transplanted patients. New
      pharmacological approaches are necessary to solve these questions.

PMID- 14697959
TI  - Positron emission tomography for detecting occult hepatocellular carcinoma in
      hepatitis C cirrhotics awaiting for liver transplantation.
AB  - Patients with hepatitis C cirrhosis may sometimes have persistently elevated
      alpha feto protein (AFP) despite a lack of evidence for disease by ultrasound or
      computed tomography (CT). While this pattern may represent a benign manifestation
      of hepatitis C cirrhosis (HCC), it raises concern for the possibility of an
      occult hepatocellular carcinoma. It has previously been shown that positron
      emission tomography (PET scan) may detect occult cholangiocarcinoma in high-risk
      patients with primary sclerosing cholangitis. We hypothesized that PET scanning
      might similarly serve for occult HCC in hepatitis C cirrhotics. PET scanning was
      performed on eight hepatitis C cirrhotics who were on the liver transplantation
      list and displayed persistently elevated AFP (>100 ng/mL) but no detectable
      lesions on abdominal CT scan. The results of PET detection of occult HCC were
      compared to those obtained with lipiodol-enhanced CT scanning and with histologic
      examination of the live explant. Explant histology or prolonged clinical follow
      up showed two subjects to have conclusive evidence of HCC; the remainder, no
      evidence of malignancy. Although PET imaging did not reveal abnormal lesions in
      any subject; lipiodol-enhanced CT scans revealed abnormal lipiodol retention in
      both subjects with HCC. These preliminary findings suggest that PET has no role
      in detecting occult HCC in high-risk patients. Additionally, these data suggest
      that some hepatitis C cirrhotics with persistently elevated AFP but no detectable
      lesions by conventional CT scan may show occult HCC using lipiodol-enhanced CT
      scans.

PMID- 14697960
TI  - Survival and resource utilization in liver transplant recipients: the impact of
      admission to the intensive care unit.
AB  - The organ allocation system for liver transplantation was recently changed to
      address criticisms that it was too subjective and relied too heavily on total
      waiting time. The new system, Model for End-Stage Liver Disease and Pediatric
      Model for End-Stage Liver Disease (MELD/PELD), stratifies patients based on the
      risk of 3-month pretransplant mortality, allocating livers thereby. There is
      concern that such a scheme gives priority to the sickest patients, who may not
      enjoy good posttransplant outcomes. The aim of the present study was to compare
      the outcomes of liver transplant recipients who had been admitted to the
      intensive care unit (ICU) to those who had not. Admission to the ICU is
      considered here to be another indicator of the severity of illness. Patients who
      underwent liver transplantation at the Cleveland Clinic between January 1, 1993
      and October 31, 1998 and were at least 18 years of age were coded for liver
      transplantation as status 2, 2A, and 2B (n = 112). These patients fell into three
      groups: those who had been admitted to an ICU before transplantation (group A, n
      = 16), those who had been admitted to the hospital but not to an ICU (group B, n
      = 63), and those who were living at home and had undergone an elective transplant
      (group C, n = 33). Clinical and demographic information (age, sex, race, disease
      severity, disease etiology, and cold ischemia time) were associated with patient
      survival, patient/graft survival, and posttransplant resource utilization
      (hospital length of stay and hospital charges). Age, sex, race, etiology of
      disease, and cold ischemia time were similar among the three groups. Patient
      survival, patient/graft survival, and hospital charges were not statistically
      different between the three groups. The median length of stay was statistically
      different only between groups B and C (P =.006). Our data support the idea that
      if severely ill patients with end-stage liver disease are selected appropriately,
      liver transplant outcomes are similar to those observed among subjects who are
      less ill and are transplanted electively from home.

PMID- 14697961
TI  - Living related liver transplantation in 13 cases of progressive familial
      intrahepatic cholestasis.
AB  - Progressive familial intrahepatic cholestasis (PFIC) is a heterogenous group of
      disorders with various etiologies. Recent molecular and genetic studies have
      categorized the spectrum of types. Liver transplantation is a curative modality
      of treatment in this disease. We report our experience with 13 patients with PFIC
      who underwent living related liver transplantation. The follow-up periods ranged
      from 12 to 50 months. Two children died at 1 and 2 years posttransplantation,
      leading to a decrease in survival rate from 100% in the first year to 84.6%.

PMID- 14697962
TI  - Duct-to-duct biliary anastomosis for patients with sclerosing cholangitis
      undergoing liver transplantation.
AB  - BACKGROUND: Due to the association of strictures within the biliary ductal
      system, Roux-en-Y choledochojejunostomy has been the preferred method of
      anastomosis for liver transplant recipients with primary sclerosing cholangitis
      (PSC). The aim of this study was to evaluate duct-to-duct anastomosis in patients
      with PSC who undergo liver transplantation. METHODS: Data were collected and
      evaluated based on demographics, type of anastomosis preformed, malignancies,
      outcomes comparisons, and survival. RESULTS: Of the 60 patients transplanted for
      PSC, 58 were diagnosed PSC prior to transplantation and 2 were diagnosed on
      explant. The Roux-en-Y group (n = 38) were similar in age, gender, and race when
      compared to the duct-to-duct (d-d) group (n = 22). There were similar rates of
      anastomotic revisions when comparing d-d anastomosis with Roux-en-Y (2 [9.1%]
      versus 2 [5.3%], P = NS) owing to bile leaks. Based on radiologic interventions
      of the bile ducts, seven (18.4%) in the Roux-en-Y group had interventions
      compared to two (9.1%) in the duct-to-duct group (P = NS). There was also no
      difference in recurrence of PSC: three (7.9%) in the Roux-en-Y group compared to
      two (5.3%) in the duct-to-duct group (P = NS). Survival at 4 years were similar
      between each group (76.5% [+/- 0.07] Roux-en-Y versus 84.9% [+/- 0.08] duct-to
      duct, P = NS). CONCLUSION: Duct-to-duct anastomosis at the time of liver
      transplantation is both safe and efficacious when used in patients with PSC.
      Outcomes as described by surgical interventions, radiologic interventions,
      retransplantation, and survival were similar between groups.

PMID- 14697963
TI  - Liver transplantation in a patient with Budd-Chiari syndrome secondary to factor
      V Leiden mutation.
AB  - A point mutation in the factor V Leiden gene is the most common hereditary
      thrombophilic state and an important risk factor for Budd-Chiari syndrome. We
      report on a patient with Budd-Chiari syndrome secondary to factor V Leiden
      mutation, who underwent successful liver transplantation. Following liver
      transplantation, his thrombophilic state was corrected and he did not require
      anticoagulation therapy. There has been no recurrent venous thrombosis for 14
      months after transplantation. Although his activated protein C sensitivity was
      normal, showing the normalization of protein C-factor V interaction, PCR analysis
      demonstrated that heterozygosity for factor V Leiden mutation was still present.
      We suggest checking resistance to activated protein C, rather than PCR analysis
      of factor V Leiden mutation in patients with Budd-Chiari syndrome after liver
      transplantation; the presence of the second does not effect clinical outcome.

PMID- 14697964
TI  - Combined twice-daily plasma exchange and continuous veno-venous hemodiafiltration
      for bridging severe acute liver failure.
AB  - Aiming to remove the toxins produced during the course of severe hepatic failure,
      we combined hemodiafiltration and plasma exchange (patient plasma replaced by
      fresh frozen plasma in a twice-daily regimen) for treatment of five patients: two
      affected by primary nonfunction of a liver graft and three by fulminant hepatic
      failure. The simultaneous use of the two extracorporeal techniques allowed a
      rapid reduction in the administration of vasoactive drugs and a rapid,
      significant decrease in the indices of liver necrosis. Native liver functional
      recovery occurred in one case, and the wait for a second graft was made possible
      in the other four. Although it has been reported that the detoxifying efficacy of
      plasma exchange is optimal when the replaced volume of plasma is high, such a
      technique requires both long treatment times and high blood flows in the
      extracorporeal circuit, making it often hemodynamically intolerable. Our approach
      leads to replacement of smaller volumes, allowing lower blood flows that are
      better tolerated despite the often unstable hemodynamics of these patients. Liver
      transplantation and retransplantation remains the definite therapy for severe
      liver failure or primary nonfunction. However, the organ waiting time is
      unpredictable and often does not coincide with the patients' clinical needs. Thus
      alternative strategies must be developed until a suitable donor is found or there
      is spontaneous recovery. From this point of view, in our albeit limited
      experience, twice-daily plasma exchange combined with hemodiafiltration has
      proved to be an effective therapeutic approach.

PMID- 14697965
TI  - Portal vein pressure and graft oxygen consumption monitoring during liver
      transplantation.
AB  - Abnormal splanchnic circulation (ASC) is often detected too late, when hepatic
      circulation is already irreversibly compromised. If we could detect surgical or
      metabolic problems early after graft reperfusion, we might be able to correct
      them immediately before the damage becomes irreversible. The aim of this study
      was to determine if ASC can be predicted early after liver transplantation (LT)
      using portal vein pressure measurements and graft oxygen consumption monitoring.
      PATIENTS AND METHODS: Twenty-patients (13 men, 7 women of mean age 46 years)
      undergoing LT with the piggyback technique for hepatitis C virus (HCV)/hepatitis
      B virus (HBV)-related cirrhosis were retrospectively divided in two groups. Group
      A (16 patients), in which LT was successful, and group B (4 patients) in which LT
      was unsuccessful because of primary nonfunction (2 patients), infrahepatic portal
      vein thrombosis (1 patient), or hepatic vein kinking (1 patient). We then
      compared the portal blood pressure values and the prehepatic and posthepatic
      oxygen content difference (p-pDO(2)) before portal clamping; at the end of
      anhepatic phase; 5, 15, and 25 minutes after portal vein (PV) reperfusion; and 5,
      20, 40, and 100 minutes after hepatic artery anastomosis. RESULTS: Early after
      graft reperfusion; portal pressure decreased to levels lower than that at
      baseline in group A, but remained high until the end of surgery in group B. At
      the end of surgery, p-pDO(2) increased more among group B than group A.
      CONCLUSION: ASC, specifically an increased PV resistance, can be predicted early
      after LT by portal vein pressure measurements and graft oxygen consumption
      monitoring.

PMID- 14697966
TI  - Perioperative cytokines during orthotopic liver transplantation without
      venovenous bypass.
AB  - Since most of studies investigating cytokine levels during human orthotopic liver
      transplantation used venovenous bypass (VVB), it may be difficult to distinguish
      between the increase in proinflammatory mediators induced by VVB, by ischemia
      reperfusion injury or by splanchnic venous congestion in the anhepatic phase. The
      goal of this investigation was to assess the levels of interleukin-6 (IL-6) and
      soluble interleukin-2 receptors (sIL-2r) during OLT procedures routinely
      performed without VVB. PATIENTS AND METHODS: Twenty-one consecutive patients
      underwent OLT with cross clamping of the inferior caval vein without VVB. Soluble
      IL-2r concentrations were measured by means of luminescence enzyme immunometric
      assay and IL-6 by means of a sequential immunometric assay. Time points (TP) of
      sampling were before induction of anesthesia (TP1), after cross-clamping of the
      inferior vena cava (TP2), 15 minutes after reperfusion (TP3), and 24 hours after
      the transplant procedure (TP4). RESULTS: Soluble IL-2r increased significantly 24
      hours after transplantation (P =.02) compared to TP1, TP2, and TP3. IL-6
      increased significantly during the anhepatic period (TP2 vs TP1, P =.003) and
      again in the reperfusion period (TP2 vs TP3, P =.002). Twenty-four hours after
      surgery IL-6 declined significantly (TP3 vs TP4, P =.001), but remained
      significantly higher (P = 0.04) compared to TP1. Furthermore, we examined the
      relative changes (DeltaTP %) in perioperative levels of cytokines compared with
      those previously published in studies using VVB. We observed higher values of
      DeltaTP % of IL-6 in TP2 and TP4 among our group of patient without VVB. The data
      on sIL-2r were similar, suggesting no major effects of the operative technique on
      sIL-2r levels. CONCLUSION: The two interleukins showed different perioperative
      trends. Our data suggest that cross clamping contributes more to cell activation,
      namely, increased release of IL-6 in the anhepatic phase than the use of VVB.
      However, no major differences were observed during the reperfusion period. The
      extent of clinical effect on graft function of higher IL-6 levels in the
      anhepatic period among recipients not supported with VVB remains to be clarified.

PMID- 14697967
TI  - Hepatocyte growth factor in hepatic allograft biopsies: an immunohistochemical
      study.
AB  - Hepatocyte growth factor (HGF) is a multipotent growth factor that is a powerful
      stimulator of DNA synthesis in a variety of cell types, especially hepatocytes.
      This factor is produced by nonparenchymal cells in the liver, presumably Kupffer
      cells, Ito cells, and sinusoidal endothelial cells. Research has shown that HGF
      is involved in tissue regeneration, wound healing, normal tissue growth, tumor
      progression, embryogenesis, and tumor invasion. Elevated serum levels of HGF have
      been documented in patients with acute renal failure and in renal transplant
      recipients; however, the importance of HGF in liver transplantation is unknown.
      The aim of this study was to determine whether induction of HGF expression is
      associated with acute rejection in liver transplants. We assessed the presence
      and density of HGF in hepatic allograft biopsy specimens compared with those from
      a control group of healthy patients.

PMID- 14697968
TI  - Influence of Th1, Th2, and Th3 cytokines during the early phase after liver
      transplantation.
AB  - To investigate the change of Th1, Th2, Th3 cytokines during early liver
      transplantation. IFN-r, IL-4, TGF-beta production by CD4+ T cells were determined
      by fluorescence activated cell sorter analysis. Comparing the acute rejection
      with the non-acute rejection groups on the 7th, 14th, and 28th day showed that
      high interferon-gamma production associated with acute rejection in the early
      posttransplant period. There was no evidence of significant changes in
      interleukin-4 and transforming growth factor beta (TGF-beta) levels between non
      acute rejection groups with acute rejection groups. Th1 cytokine high production
      is significantly associated with acute rejection in liver transplant recipients.

PMID- 14697969
TI  - Reduction of naive CD4/CD45RA+ T cells in children with biliary atresia before
      and after liver transplantation.
AB  - The aim of this study was to examine whether liver transplantation reverses the
      abnormal distribution of lymphocyte subsets previously observed in biliary
      atresia children, namely a selective decrease in the naive CD4/CD45RA+ T cell
      subset and an increase in the B and natural killer cell subpopulations. Eight
      biliary atresia children aged 1.08 to 6 years were studied before and 1 year
      after LTx for comparison with 15 age-matched healthy controls. The posttransplant
      immunosuppressive regimens included prednisone [0.1 mg/kg] and tacrolimus (level
      range: a 10-12 microg/dL). The percentage, absolute cell number, and receptor
      density were assessed by the use of double color flow cytometry (EPICS-XL MCL
      fluorocytometer). Biliary atresia patients were compared after LTx with subjects
      before LTx, essentially showing no statistically significant changes in
      lymphocyte subsets. We conclude that LTx of biliary atresia children does not
      reverse the abnormal lymphocyte subset distribution present before
      transplantation. Hence, these changes may reflect either their independence from
      the liver status or may result from immunosuppressive treatment that contributes
      to defective CD4+ T cell regeneration reflected by a deficiency in CD4/CD45RA+
      naive T cells.

PMID- 14697970
TI  - Sirolimus therapy in orthotopic liver transplant recipients with calcineurin
      inhibitor related chronic renal insufficiency.
AB  - Calcineurin inhibitor-related renal toxicity affects patient and graft survival
      in transplant recipients. Our clinical experience has revealed sirolimus to be an
      effective agent in treating renal insufficiency related to calcineurin inhibitor
      toxicity. METHODS: We performed a retrospective review of the medical records of
      OLT recipients suffering from chronic renal insufficiency and treated with
      sirolimus at the University of Miami. RESULTS: Fourteen patients (nine men and
      five women) of mean age 57 years who had been treated with tacrolimus for at
      least 30 days were converted to sirolimus after developing nephrotoxicity. Mean
      creatinine clearances collected on day 0, 30, 60, and 90 after conversion were
      40.1 mL/min, 49.6 mL/min, 53.9 mL/min, and 51.4 mL/min, respectively. Episodes of
      acute cellular rejection were not increased during the sirolimus conversion.
      CONCLUSION: This retrospective review suggests that OLT patients suffering from
      tacrolimus-related renal insufficiency successfully converted to sirolimus may
      benefit from this therapy.

PMID- 14697971
TI  - Does conversion of immunosuppressive monotherapy from cyclosporine A to
      tacrolimus improve bone mineral density in long-term stable liver transplant
      recipients?
AB  - The effects of converting cyclosporine A to tacrolimus on bone mineral density
      (BMD) have not yet been evaluated thoroughly in liver transplant patients.
      Interfering factors in this patient population often are concomitant
      glucocorticoid treatment or exposure to estrogens. Here, we investigated in a
      homogeneous population of 10 male liver transplant recipients the impact of
      converting low-dose cyclosporine A monotherapy to low-dose tacrolimus monotherapy
      on BMD by using dual-energy x-ray absorptiometry. During the 12-month study
      period, an increase in BMD at the lumbar spine was observed in 9 out of 10 men (P
      <.01), whereas BMD at the femoral neck remained stable. Converting cyclosporine A
      to tacrolimus appears to be safe and efficaceous with regard to maintaining or
      even increasing BMD in male liver transplant recipients.

PMID- 14697972
TI  - Should we biopsy kidneys of patients post-liver transplant?
AB  - Thirty days after orthotropic liver transplantation, a 52-year-old Hispanic male
      developed full-blown nephrotic syndrome. Although the patient was
      posttransplantation, he underwent a kidney biopsy under real-time ultrasound
      guidance. The pathological specimen revealed membranous nephropathy. A change in
      the immunosuppressive regimen resulted in a rapid decrease in urinary protein
      excretion, leading to resolution of the nephrotic syndrome. We report this case
      to illustrate the precautions that need to be taken when liver transplant
      patients require a kidney biopsy.

PMID- 14697973
TI  - Allergic disease after pediatric liver transplantation with systemic tacrolimus
      and cyclosporine a therapy.
AB  - Cyclosporine A (CsA) and tacrolimus (Tac), both calcineurin inhibitors, have been
      used extensively for immunosuppressive therapy in pediatric liver transplant
      recipients. They share a similar mechanism of action, the inhibition of cytokine
      gene transcription primarily interleukin-2 (IL-2) in T lymphocytes. Despite the
      strong immunosuppressive property, there are several reports of food allergy in
      pediatric transplant recipients under Tac immunosuppression, but not CsA. In this
      paper we report on 3 of 50 pediatric liver transplant recipients diagnosed with
      food allergy and asthma while receiving systemic Tac/CsA immunosuppression and
      the discuss the role of calcineurin inhibitors in this situation.

PMID- 14697974
TI  - Pilot study of pegylated interferon alfa-2b and ribavirin for recurrent hepatitis
      C after liver transplantation.
AB  - Recurrent hepatitis C is often treated with an interferon and ribavirin
      combination therapy, but the results have been disappointing. Given the promising
      results reported with pegylated interferon and ribavirin for hepatitis C, we were
      interested in evaluating the effectiveness of this treatment in liver transplant
      recipients with recurrent hepatitis C (HCV). METHODS: Between November 2001 and
      September 2002, patients with recurrent HCV were screened to determine if they
      were eligible for treatment. Liver function tests, HCV-RNA, and liver biopsies
      were performed on all patients prior to treatment. HCV-RNA was repeated at 3
      months, the end of treatment (EOT), and 6 months after EOT for patients who were
      HCV-RNA negative at EOT. Patients were prospectively followed after starting
      weekly pegylated interferon alfa-2b 1.5 mcg/kg per week and ribavirin 800 mg per
      day (Schering-Plough, Kenilworth, NJ, USA) with folic acid 1 mg per day. RESULTS:
      Thirty-nine patients eligible for treatment displayed a median age of 50.4 years.
      Eighteen patients completed treatment, 4 remain on treatment, and 17 were
      intolerant. Sustained HCV-RNA eradication occurred in 66.7% of patients who
      completed treatment. Side effects led to treatment withdrawal in 17 patients
      (43.6%) In an intention-to treat analysis, sustained HCV-RNA eradication occurred
      in 30.8% of patients. CONCLUSION: Side effects are an important limiting factor
      in the treatment of recurrent HCV with pegylated interferon and ribavirin.
      However, these results are encouraging as sustained HCV eradication occurred in
      at least 66.7% of patients who completed treatment. Prospective randomized trials
      are required to assess the effectiveness of this treatment and its impact on
      quality of life and histology.

PMID- 14697975
TI  - Prevalence of liver complications in pediatric patients on home parenteral
      nutrition: indications for intestinal or combined liver-intestinal
      transplantation.
AB  - Parenteral nutrition (PN) is the only treatment for patients affected by chronic
      intestinal failure (CIF). Home parenteral nutrition (HPN) programs are started
      when patients need prolonged PN. Unfortunately, many patients on prolonged PN
      develop liver disease (LD). The aim of our study was to assess the prevalence of
      LD in our series of patients on HPN. We reviewed our records of patients
      discharged from the hospital on HPN for CIF. HPN was started when one parent was
      fully trained in the use of this treatment and if the social and familial home
      environment was reliable. All patients received total PN by a central venous
      catheter. All patients with abnormal AST, ALT, ALK, gammaGT, and bilirubin values
      for more than 3 months were considered affected by PN-related LD. Thirty-six
      patients (23 of whom were boys and 13 girls) were discharged on HPN. During the
      study period, for CIF, 16 were affected by short bowel syndrome (SBS), of whom 6
      had ultra-short bowel; 16 with functional intestinal failure, and 4 with chronic
      intestinal pseudobstruction (CIPO). Mean duration of HPN was 2.1 years/patient.
      Nine of 36 patients (25%) on HPN for CIF showed LD. Seven of the 16 patients
      (43%) with LD were affected by SBS and 2 (12.5%) patients by functional
      intestinal failure. No patients with CIPO developed LD. In patients affected by
      SBS, the onset of LD was very earlier than in patients with ID.

PMID- 14697976
TI  - Complications of home parenteral nutrition in a large pediatric series.
AB  - When adequate nutrition cannot be provided by enteral route as a consequence of
      failure of intestinal functions, parenteral nutrition (PN) become the only way to
      maintain adequate nutrition; however, prolonged periods of PN can lead to severe
      complications. Furthermore, long hospital admissions for this form of nutrition
      can be detrimental for the child and the family. In the past 20 years, home
      parenteral nutrition (HPN) programs have been developed. The aim of our study was
      to retrospectively evaluate the kind and the frequency of complications in a HPN
      pediatric case series. We had 61 patients on HPN. Total duration of the program
      was 27,740 days (76 total years, mean 1.2 years per patient). We observed a total
      of 58 complications; mean 0.79 per patient per year with a prevalence of central
      venous catheter-related complications (mechanical, 52%; infective, 26%). We had a
      very low incidence of metabolic complications (3%) and a low incidence of PN
      related hepatic complications (19%). None of the complications described was the
      cause of death. Half of our patients have been able to stop the program. We had a
      low incidence (0.20 per patient per year) of septic episodes, lower than we had
      in patients on hospital PN in the same period (0.38 per patient per year). We had
      to replace 20 catheters, 18 of them for mechanical problems. Our study shows that
      HPN still can be a valid alternative to small intestinal transplantation in
      patients affected by intestinal failure and that only patients with PN-related
      liver disease must be considered early candidates for combined liver-small bowel
      transplant.

PMID- 14697977
TI  - Intractable diarrhea of infancy with congenital intestinal mucosa abnormalities:
      outcome of four cases.
AB  - Microvillous inclusion disease (MID) and epithelial dysplasia (ED) or tufting
      enteropathy are the most frequent causes of intractable diarrhea with persistent
      villous atrophy and indefinite dependence on total parenteral nutrition (PN) from
      early infancy. Since these are intractable diseases, they have been proposed to
      be elective indication for early bowel transplantation in order to avoid
      complications, such as PN-related liver disease, that would require a combined
      small bowel-liver transplant. We describe four cases of intractable diarrhea, two
      with MID and two with ED, seeking to discover whether these diseases are really
      elective, early indications for bowel transplant. Among our four patients, only
      one with ED underwent transplantation. The prognosis of small bowel transplant is
      still poor and worse than that of prolonged HPN. Further study is necessary to
      achieve a safe HPN program. Referral for transplant (small bowel only or combined
      with liver) should be considered when there is a venous access reduction and/or
      severe and irreversible liver disease.

PMID- 14697978
TI  - Evaluation of the outcomes of short bowel syndrome and indications for intestinal
      transplantation.
AB  - Long-term parenteral nutrition (PN) and intestinal transplantation (IT) are life
      saving therapies for patients with short bowel syndrome (SBS). However,
      indications and timing of these therapies are controversial. In this study we
      aimed to evaluate the indications for IT. Forty-two patients, each with <100 cm
      of small bowel, were divided into three groups according to the length of
      remnant: group I patients (n = 18): colon plus 50 to 100 cm of small bowel (SB);
      group II patients (n = 14): colon plus <50 cm of SB; and group III patients (n =
      10): <50 cm of SB without colon. One-year mortality rates for groups I, II, and
      III were 50%, 72%, and 100%, respectively. All group I survivors developed
      intestinal adaptation, returning to regular oral feedings at 1 year.
      Interestingly, three of four surviving patients in group II developed adaptation
      and were fed an oral short bowel diet (SBD) at 1 year. None of the group III
      patients survived >1 year, dying due to multiorgan failure in the early
      postoperative period or from sepsis within 1 year. We conclude that patients with
      a very short bowel are candidates for IT when stable. If the colon is intact,
      however, regardless of small bowel remnant length, the patient should be given a
      chance to develop intestinal adaptation before making the decision for permanent
      PN or IT.

PMID- 14697979
TI  - Sclerosing mesenteritis in small bowel transplantation: possible manifestation of
      acute vascular rejection.
AB  - BACKGROUND: Acute rejection of human small bowel allografts is characterized by
      clinical symptoms combined with characteristic morphologic alterations. The
      typical geographic distribution of acute rejection in the bowel is involvement of
      the intestinal parenchyma, which can be transmural, particularly when the
      rejection is more severe. However, little is known concerning the potential for
      donor-derived soft tissue adjacent to the bowel to become involved by the host
      alloimmune response. METHODS: We describe a male patient who, several weeks after
      combined small bowel and liver transplantation, demonstrated sclerosing
      mesenteritis with vasculitis and acute rejection of the bowel. RESULTS: The
      vascular lesions in the mesentery demonstrated increased IgG deposition and the
      patient developed an alloantibody to the donor. CONCLUSIONS: The changes
      described herein may represent a novel presentation of acute vascular rejection.

PMID- 14697980
TI  - Granzyme B and perforin as predictive markers for acute rejection in human
      intestinal transplantation.
AB  - In human heart and kidney transplantations, granzyme B (GrB) and perforin have
      both been shown to be predictive markers for acute cellular rejection (ACR). We
      investigated the tissue expression and possible relationship of GrB and perforin
      to the clinical outcome, histopathology, and function of intestinal transplants.
      In 13 consecutive patients undergoing small intestine transplantation,
      histologic/immunohistochemical rejection monitoring was performed together with
      GrB and perforin immunostaining (score "0", 0%-10% positive lymphocytes; "1", 10%
      25%; "2", 25%-50%; "3", >50%). Eleven patients are currently alive and well. All
      11 had at least one episode of ACR: one patient had 6 episodes of severe ACR
      requiring retransplantation; the remaining 10 experienced only mild or moderate
      rejection. Both GrB and perforin were always co-expressed. A highly significant
      correlation was observed between GrB/perforin scores and histological severity of
      ACR (Pearson's coefficient, R < 0.0009). Interestingly, score 3 GrB/perforin
      immunostaining was recorded only in the context of severe ACR; all the
      histologically negative or "indeterminate" biopsies (n = 6) taken from a single
      affected patient showed GrB/perforin scores of 1 or 2. By contrast, none of the
      other tested histologically negative/"indeterminate" biopsies (n = 350),
      including those performed during graft stabilization, had raised GrB or perforin
      scores. We conclude that in intestinal transplantation recipients, a direct
      correlation seems to exist between histologically confirmed ACR and raised
      GrB/perforin immunohistochemical scores. Our findings suggest the need to
      investigate the possibility of predicting ACR by routine serum polymerase chain
      reaction (PCR) monitoring, which would reduce discomfort to patients.

PMID- 14697981
TI  - Challenges in heart transplantation: now and the future.
AB  - Little more than 30 years after the first human operation, heart transplantation
      continues to be the gold standard treatment for heart failure disease. During
      these years, surgical procedures and immunosuppressive treatment have improved
      and the survival rate continues to improve despite transplanting older and sicker
      patients. However, there are still many challenges that we are currently facing.
      Regarding organ shortage, donor heart acceptance criteria have been reconsidered.
      Better donor management could increase the organ pool, maximizing the use of
      hearts recovered from cadaveric donors. Concerning organ allocation, recent
      improvements in medical treatment could restrict transplantation procedures to
      the patients at greatest risk of dying. Controlling allograft rejection,
      vasculopathy, and malignancies are current challenges. Cyclosporine,
      azathioprine, and corticosteroids have been the mainstay of immunosuppression,
      but carry severe adverse systemic effects. Today, new pharmacologic agents have
      become available and hold the possibility to improve the length and quality of
      recipient life.

PMID- 14697982
TI  - Alteration of the left ventricular contractile reserve in heart transplant
      patients: a dobutamine stress strain rate imaging study.
AB  - BACKGROUND: Strain rate imaging (SRI), a recently developed Doppler-derived
      process, allows quantification of myocardial systolic function. We investigate
      whether SRI quantifies the contractile reserve during dobutamine stress tests in
      heart transplant patients (HT), when compared with normal individuals. METHODS:
      An incremental dobutamine test (5 to 40 microg/kg per minute) was performed in 10
      HT and 15 control subjects, all of whom displayed normal coronary angiography.
      Gray-scale and color myocardial Doppler data were acquired in standard B-mode
      views at baseline, low-dose, peak, and recovery. Longitudinal SR was processed
      from the myocardial velocities for each segment. The changes in maximal systolic
      SR were used to quantify myocardial contractile reserve. RESULTS: Dobutamine
      infusion failed to induce clinical symptoms or electrocardiographic (ECG) changes
      in either group. Visually determined wall motion score was considered normal in
      all segments for each stage of the dobutamine stress. Heart rate was augmented
      similarly in both groups during dobutamine infusion. In controls, systolic SR
      increased gradually with incremental dobutamine dose and returned to baseline
      values upon recovery. Conversely, in HT patients, the increase in systolic SR was
      blunted at peak dobutamine, at which point it was significantly different vs
      controls. CONCLUSIONS: Quantitative assessment of myocardial function using SRI
      during dobutamine stress revealed an impaired contractile reserve in HT patients
      with normal coronary angiography. These subtle changes in regional myocardial
      function could not be identified using visual wall motion scoring. Additional
      studies are necessary to evaluate whether SR imaging detection of contractile
      reserve impairment will improve clinical efficiency or event prediction in this
      population.

PMID- 14697983
TI  - Utility of biochemical markers in the follow-up of heart transplant recipients.
AB  - Endomyocardial biopsy (EMB) is currently the standard method to diagnose acute
      graft rejection. However, considering the potential complications of this
      procedure, a noninvasive marker of rejection would be an ideal alternative or at
      least a helpful adjunct to posttransplant management. We measured myoglobin
      (Myo), creatine kinase MB mass (CK-MBm), troponin T (cTnT), serum amyloid A
      (SAA), and C-reactive protein (CRP) in 57 patients (mean age 37.5 years) who
      underwent orthotopic heart transplantation for end-stage cardiac failure between
      January and December 2001.Endomyocardial biopsies were performed routinely after
      surgery and histologically diagnosed rejection was graded according to the
      criteria of the International Society of Heart and Lung Transplantation.
      Concomittant with the biopsies, blood samples were drawn from the coronary sinus
      (central blood samples) and from a peripheral vein (peripheral blood samples) to
      assay biochemical markers. Among 149 EMB evaluated, 87 were negative (grade 0);
      28 showed grade 1a rejection; 26 showed grade 1b; and 8 showed grade > 1b (2 were
      grade 2, 6 were grade 3a). Grades 0 and 1a were considered to be negative, while
      grades 1b and >1b were considered positive indicating potential acute graft
      rejection. cTnT, Myo, CK-MBm, SAA, and CRP levels were measured in 149 central
      blood samples and 149 peripheral blood samples. Myo and CK-MBm did not show
      significant changes. cTnT seems to be a potentially useful addition to the EMB
      results, while SAA and CRP showed variations with respect to EMB grade both in
      central and peripheral samples.

PMID- 14697984
TI  - Improved ultrasound examination of pancreas grafts in type 1 (insulin-dependent)
      diabetic patients using tissue harmonic imaging.
AB  - BACKGROUND: Combined kidney/pancreas transplantation is an established therapy
      for type 1 diabetic patients with end-stage renal disease. Ultrasound
      examinations are valuable noninvasive methods for postoperative monitoring of
      transplant recipients. Kidney grafts are easily to detect, whereas pancreas
      grafts are surrounded or covered by small bowel loops, which makes the
      examination much more difficult. PATIENTS AND METHODS: Thirty-three simultaneous
      pancreas and kidney recipients (SPK) were examined by conventional sonography at
      3.4 MHz and THI sonography (pulse inversion, 2.3 MHz) by an investigator
      experienced in abdominal ultrasound. The images were graded by two "blinded
      readers" using a scale (1-best image quality, 2-second best, 3-worst) with regard
      to tissue penetration and detail characterization of the pancreas grafts. The
      graders were unaware of the sonographic technique, respectively. Statistical
      evaluation was performed by the Mann-Whitney U test. RESULTS: In 25 cases (78%)
      pancreas grafts were detected by conventional sonography. The detection rate was
      higher using THI sonography, namely 29 cases (91%). Grading for tissue
      penetration revealed a mean value of 2.05 +/- 0.5 for conventional and 1.94 +/-
      0.5 for THI sonography (P =.27). Detail characterization of the pancreas grafts
      was determined to show a mean value of 2.50 +/- 0.5 for conventional sonography
      and a significantly better mean value of 1.78 +/- 0.6 for THI sonography (P
      <.0001). CONCLUSION: THI sonography improves the detection and the judgment of
      tissue characteristics of pancreas grafts. Penetration of ultrasound waves is not
      relevantly decreased by this new technique.

PMID- 14697985
TI  - Effect on growth parameters of bone marrow transplantation with a chemotherapy
      only conditioning regimen.
AB  - INTRODUCTION: The increasing use of bone marrow transplantation (BMT) has
      increased survival among a growing number of children and young adults afflicted
      by malignant and nonmalignant hematologic disorders. Accordingly, quality of life
      has emerged as an important issue. Because they are a concern in this group, we
      assessed growth and development, following chemotherapy-only conditioning
      regimens. MATERIALS AND METHODS: Twelve prepubertal children (8 boys, G(1)P(1)
      and 4 girls, B(1)P(1)) with a mean age of 6 +/- 2 years (age range: 3.5 to 10
      years) before and at 3, 6, 9, and 12 months post-BMT. RESULTS: Growth velocity at
      1 year posttransplant was 10.0 +/- 3.5 cm/y. One year post-BMT, the statistical
      deviation saturation for growth velocity was 4.31 +/- 4.21. Height standard
      deviation score was -1.4 +/- 1.2 before and -0.5 +/- 1.3 1 year post-BMT (P
      <.004). The average weight of our subjects was 20 +/- 6 kg before and 26 +/- 9.5
      kg 1 year post-BMT. DISCUSSION: BMT with a chemotherapy-only conditioning regimen
      not only does not disturb growth in children; it is actually associated with a
      relative growth spurt afterward.

PMID- 14697986
TI  - Autologous bone marrow transplant in a patient with sickle cell disease and
      diffuse large B-cell lymphoma.
AB  - As the life expectancy of patients with homozygous sickle cell anemia (SCA)
      improves, SCA care providers are confronted with diseases of the adult SCA
      population rarely seen before. We report here a 40-year-old woman with SCA who
      developed diffuse large B-cell non-Hodgkin's lymphoma (NHL) that was treated with
      eight cycles of chemotherapy consisting of cyclophosphamide, doxorubicin,
      vincristine, prednisone, and etoposide (CHOPE), without complete remission. She
      subsequently underwent high-dose cyclophosphamide and total-body irradiation
      followed by autologous bone marrow transplantation (BMT). To reduce the risk of
      sickle cell crisis precipitated by G-CSF, she underwent hypertransfusion to
      maintain a low % hemoglobin S throughout her treatment course. Although she has
      required iron chelation therapy and shows no sign of modification of her
      underlying SCA, she remains in remission from NHL 12 years posttransplant. To our
      knowledge, this is the first reported case of autologous BMT in a patient with
      SCA. Our patient illustrates that SCA in itself does not preclude autologous stem
      cell transplantation for lymphoma in selected patients, and this report should
      encourage others to consider autologous BMT in adults with SCA where it
      represents a lifesaving therapy for malignant diseases.

PMID- 14697987
TI  - B-cell lymphoproliferative syndrome and peripheral blood CD20+ cells expansion
      after hematopoietic stem cell transplantation: association with fludarabine and
      anti-thymocyte globulin containing conditioning regimen.
AB  - Fifty-eight patients who received hematopoietic stem cell transplants during a 3
      year period in our unit were followed for the symptoms of posttransplant B-cell
      lymphoproliferative syndrome (B-cell PTLD). Three cases showed lymph node
      enlargement; in 14, there was an excess of B cells in the blood. Histochemical
      staining of lymph nodes revealed CD20+ cell expansion in two cases, and in one,
      CD38+ and CD138+ cells. Kappa and lambda staining revealed poly- or oligoclonal
      expansion, which was characterized by the presence of Ki67+ cells in 10% to 50%
      of cells. In 14 cases, an excess of CD20+ cells were observed in blood. Clinical
      analysis revealed that patients with B-cell expansion in blood and/or in lymph
      nodes frequently showed fever and that some subjects displayed arthralgia,
      hemolytic anemia, and hepatitis. LMP-1-positive cells were observed in lymph
      nodes as well as EBV copies, whereas only a proportion of patients with the
      excessive CD20+ cells in blood were EBV positive. Notably, lymph node enlargement
      and CD20+ blood excess occurred significantly more frequently among patients
      receiving a Fludarabine (Flu) and anti-thymocyte globulin (ATG) conditioning
      regimen than those whose treatment lacked Flu independent of whether they
      received ATG (0.80 vs 0.44; P =.036).

PMID- 14697988
TI  - An optimization of isolation of early hematopoietic cells from heparinized
      cadaveric organ donors.
AB  - Heparinized cadaveric organ donors are a potential source of hematopoietic cells
      for transplantation purposes. The aim of this study was to optimize the harvest
      of early hematopoietic cells from cadaver donors. Accordingly, we noticed that
      bone marrow cells harvested from cadaver donors should be resuspended in RPMI or
      Iscove's medium supplemented with heparin or ACD. Bags with harvested marrow
      should contain 20% atmosphere air during short-term storage/transportation.
      Finally, we noticed that BMMNC survive short-term storage better if the collected
      marrow is not depleted of erythrocytes.

PMID- 14697990
TI  - Magnetic resonance imaging of hyaline cartilage regeneration in neocartilage
      graft implantation.
AB  - BACKGROUND: The purpose of this study was to investigate the regenerative
      potential of hyaline cartilage in a neocartilage graft implant with the aid of MR
      cartilage imaging using a rabbit model. METHODS: Surgical osteochondral defects
      were created in the femoral condyles of 30 mature New Zealand rabbits. The
      findings of neocartilage in autologous cartilage grafts packed into osteochondral
      defects were compared with control group of no implant to the osteochondral
      defect. The outcome of the implantations was correlated with histologic and MR
      cartilage imaging findings over a 3-month interval. RESULTS: Neocartilage grafts
      packed into osteochondral defects showed regeneration of hyaline cartilage at the
      outer layer of the implant using MR cartilage imaging. Fibrosis of fibrocartilage
      developed at the outer layer of the autologous cartilage graft together with an
      inflammatory reaction within the osteochondral defect. CONCLUSION: This animal
      study provides evidence of the regenerative ability of hyaline cartilage in
      neocartilage transplants to repair articular cartilage.

PMID- 14697989
TI  - Thyroid, parathyroid, gonadal, and pancreatic beta-cell function after bone
      marrow transplantation with chemotherapy-only conditioning.
AB  - INTRODUCTION: Radiation and cytotoxic chemotherapy can provoke short- and long
      term endocrine dysfunction. We studied the prevalence of thyroid, parathyroid,
      gonadal, and pancreatic beta-cell function in patients undergoing bone marrow
      transplantation (BMT). MATERIALS AND METHOD: Forty-six patients (12 women, 34
      men), aged 1.5 to 49 years (mean, 15.1 years), were evaluated for thyroid,
      parathyroid, gonadal, and pancreatic beta-cell function before and 3, 6, and 12
      months after BMT with a little busulfan-cyclophosphamide conditioning regimen.
      RESULTS: Thyroid and parathyroid function was unaltered by BMT. Leydig cell
      function was normal in 11 adult men (G5P5) before and at 3, 6, and 12 months
      after BMT, but injury to the germinal epithelium (oligo- or azoospermia) was seen
      before and 12 months after BMT. There was no relationship between serum FSH and
      germinal epithelial injury. Maturation was normal in six boys (G2P2 or G3P3 at
      BMT) 12 months post-BMT. Primary hypogonadism was seen in four adult women (B5P5)
      after BMT. One 14-year-old girl continued to have regular menstrual periods
      during the 24 months after BMT. Another girl (P1B1 pre-BMT) developed ovarian
      failure 12 months post-BMT. Pancreatic beta-cell function was normal pre- and
      post-BMT in 12 thalassemic patients with serum ferritin > 1000 ng/mL. CONCLUSION:
      BMT with chemotherapy-only conditioning seems primarily to affect gonadal
      function, without having any significant effect on thyroid, parathyroid, or
      pancreatic beta-cell function.

PMID- 14697991
TI  - Biphasic behavior of the kinetics of 31P-containing metabolites in ischemic
      porcine kidneys.
AB  - The assessment of kidney viability before transplantation (with a view of
      discarding nonviable organs) remains an obstacle to confidently extending organ
      harvesting to marginal donors. In the present study phosphorus magnetic resonance
      spectroscopy was used to monitor metabolic changes in (31)P-containing
      metabolites in isolated porcine kidneys. After various warm ischemia times, the
      organs were stored at 0 degrees C. Time-dependent changes in the
      phosphomonoester/inorganic-phosphate ratio were recorded at 0 degrees C were
      shown to follow a biexponential decay. The first-order kinetic rate constant of
      the short-time decay was strongly dependent on the warm ischemia time, a result
      that was discreted in terms of the underlying biochemistry. The metabolic events
      responsible for the dramatic decrease in phosphomonoester/inorganic phosphate
      ratio that occur immediately after organ perfusion and storage, suggest that any
      procedure to minimize organ damage must occur immediately after harvesting.

PMID- 14697992
TI  - Epigallocatechin gallate can significantly decrease free oxygen radicals in the
      reperfusion injury in vivo.
AB  - OBJECTIVE: There is experimental evidence that oxygen-derived free radicals
      (Superoxide (O(2)(-))) play a key role in tissue damage in ischemia-reperfusion
      injury. Among various antioxidants tested in vitro, natural polyphenols like
      Epigallocatechine gallate (EGCG) show a 164-fold higher scavenging activity for
      O(2)(-) than ascorbic acid We therefore conducted an animal study in order to
      investigate the impact of EGCG on O(2)(-) production during reperfusion after
      defined periods of ischemia in the muscle tissue of the rat, using a recently
      developed cytochrome c-based biosensor for on-line in vivo monitoring of O(2)(-).
      MATERIALS AND METHODS: Femoral artery and vein were dissected below the inguinal
      ligament in male Wistar rats. The cytochrome c-based biosensor was placed in the
      gastrocnemius muscle. Ischemia was induced by clamping the femoral vessels.
      Ischemia times were either 60 (n = 14) or 120 (n = 14) minutes. Six animals in
      each group received 4 mg/kg body weight EGCG intravenously at the time of
      reperfusion, another six animals in each group served as controls (no treatment).
      Additionally, two animals in each group received the same volume of saline
      instead of EGCG. The current response of the biosensor corresponding to the O(2)(
      ) concentrations in vivo was recorded on a PC. The gastrocnemius muscles were
      harvested for histological evaluation. RESULTS: The average maximum O(2)(-)
      concentration after 60 minutes of ischemia was 188, 18 nmol/L (23 pA) compared to
      90 nmol/L (11 pA) (P <.01) with EGCG application. The mean O(2)(-) value after
      120 minutes was 220 nmol/L (27 pA) versus 135 nmol/L (16.5 pA) (P <.01) with
      EGCG, respectively. Histological analysis showed advanced muscle cell injury and
      neutrophil infiltration in the group without EGCG. No O(2)(-) reduction could be
      verified administering saline instead of EGCG. CONCLUSION: For the first time the
      scavenging activity of an antioxidant was verified in vivo on-line. EGCG
      significantly diminished O(2)(-) tissue concentrations after 60 or 120 minutes of
      ischemia by an average of nearly 50%, suggesting its therapeutic potential.

PMID- 14697994
TI  - Can ischemia-reperfusion syndrome in transplanted kidneys procured from non-heart
      beating donors be influenced by adding selenium into the reperfusion solution? An
      experimental study.
AB  - Ischemia-reperfusion syndrome significantly influences the function of a kidney
      transplanted from a non-heart-beating donor (NHBD). An animal model of NHBD was
      used to monitor the influence of the exogenous addition of selenium in the
      perfusion solution (HTK, Custodiol) on the generation of free oxygen radicals
      between 0 and 120 minutes after transplantation of the NHBD organ. During this
      interval, the malondialdehyde concentration, an indicator of free oxygen radicals
      in the venous blood of the transplanted kidney, significantly decreased. The
      augmentation of the anti-oxidant capacity of the preservation solution might
      represent a possible improvement in the function of kidneys transplanted from
      NHBDs.

PMID- 14697993
TI  - Pravastatin decreases cold ischemia--but not alloantigen-dependent transplant
      arteriosclerosis.
AB  - BACKGROUND: Alloantigen mismatch and cold ischemia have been shown to induce
      transplant arteriosclerosis. Pravastatin (PR) decreases arteriosclerosis probably
      related to an immunosuppressive effect. Statins possess other nonimmune
      properties that may be beneficial to transplantation. We studied the effect of PR
      on cold ischemia and alloantigen-induced transplant arteriosclerosis in syngeneic
      (SYN) and allogeneic (ALLO) aortic transplantation models. METHODS: Lewis rats
      served as the donors and recipients for SYN transplants and Brown Norway rats
      were donors for ALLO transplants. Aortic segments that had been preserved at 4
      degrees C in Euro-Collins solution for 0 or 24 hours were transplanted to the
      infrarenal aorta of the recipients PR (10 mg/kg/d) was administered for 12 weeks
      prior to morphometric studies. Areas of intimal thickness and its relation to
      total vessel area were calculated. Lipid levels were measured at 12 weeks.
      RESULTS: Aorta rings preserved for 24 hours showed marked intimal thickening
      compared to controls (SYN, CI 0 hours = 21.5% +/- 16.5% vs SYN, CI 24 hours =
      50.7 +/- 9.5%, P <.05). PR significantly decreased thickening (SYN, CI 24 hours +
      PR = 41.7 +/- 12.2 (P <.05) vs SYN, CI 0 hours on SYN, CI 24 hours). There was a
      nonsignificant decrease in thickening among ALLO transplants treated with PR
      (ALLO = 31.4 +/- 15.9 vs ALLO + PR = 23.8 +/- 18.8; P >.05). PR had no effect on
      lipid levels. PR decreases cold ischemia induced transplant arteriosclerosis in
      this syngeneic aortic transplant model, but does not affect an alloantigen
      mediated process. The beneficial effect of PR is not related to its lipid
      lowering properties but probably to a nonimmune effect.

PMID- 14697995
TI  - Cyclosporine A toxicity in association with reduced renal mass.
AB  - The long-term effect of cyclosporine A (CsA) in male Wistar rats with reduced
      renal mass was studied. The aim of the study was to highlight the relationship of
      CsA effect on rats, simulating patients with two functioning kidneys (eg, heart,
      liver transplant recipients) and one kidney (renal transplant recipients). The
      Wistar rats were subjected to unilateral nephrectomy (Unx, n = 14) and to 5/6
      nephrectomy (STnx, n = 14). Half of these rats and half of the sham operated ones
      (control, n = 13) were administered CsA (10 mg/kg/d) for 28 days IP. The serum
      creatinine (S(CR)), total protein (S(P)), and urine protein (U(P)) values as well
      as the whole blood CsA levels were determined on the 28th day of the study. The
      remnant kidneys were evaluated by image analyses and semiquantitative methods
      after sacrifice on the 28th day. In the three non-CsA-treated groups (Unx, STnx,
      and control) S(CR) was significantly higher in STnx rats than in Unx rats (P
      =.011). Percent of renal scarring (PRS) was significantly higher in Unx (P =.02)
      and in STnx rats (P =.017), compared with the control group. Among CsA-treated
      three groups S(CR) was significantly higher in STnx rats compared with Unx (P
      =.017). In addition, segmental sclerosis rate (SSR) was higher in STnx rats,
      compared with the control group (P =.008), whereas S(P) was higher in the control
      group (P =.005). When CsA-treated groups were compared with non-CsA-treated ones,
      U(P) of the Unx rats not receiving CsA were significantly higher than the Unx
      rats receiving CsA (P =.026). Also, U(P) was higher in non-CsA-treated groups (P
      =.014), whereas S(CR) (P =.001), S(P) (P =.001), and PRS (P =.001) were higher in
      CsA-treated rats. In conclusion, we suggest that preserved renal mass is not
      enough to prevent CsA toxicity and that CsA should be administered to patients
      with both kidneys (eg, heart, pancreas recipients) as carefully as to patients
      with one functioning kidney (renal transplant recipients).

PMID- 14697996
TI  - The Na+/H+ exchange inhibitor: a new therapeutic approach for hepatic ischemia
      injury in rats.
AB  - BACKGROUND: Na+/H+ exchanger (NHE) is one of the major mechanisms for restoring
      pH after ischemia-induced intracellular acidosis. However, activation of NHE
      during ischemia and reperfusion (I/R) is also involved in the paradoxical
      induction of cell injury. This study was designed to evaluate the effects of 5-(N
      ethyl-N-isopropyl)-amiloride (EIPA), an NHE inhibitor, on hepatic I/R injury.
      METHODS: Partial hepatic ischemia was induced in male Wistar rats by cross
      clamping the hepatic arterial and portal venous branches to the left lateral and
      median lobes of the liver for 120 minutes. The caudate and right lateral lobes
      were removed immediately after reperfusion. The concentrations of serum enzymes
      and ATP levels and energy charge in the live tissue were examined after 1-hour
      reperfusion. RESULT: EIPA afforded considerable protection against I/R injury, as
      demonstrated by decreased transaminase release and reduced histologic hepatocyte
      damage and increased energy charge. The 7-day survival rate was significantly
      improved from 15.4% to 55.6% (P <.05). CONCLUSIONS: This study shows for the
      first time that NHE may play an important role in the hepatic I/R injury and that
      EIPA should be considered as a new therapeutic approach to prevent hepatic I/R
      injury.

PMID- 14697997
TI  - Effect of sirolimus on the cholesterol content of aortic arch in ApoE knockout
      mice.
AB  - Chronic inflammatory responses involving the immune system have been implicated
      in the process of atherosclerosis. Sirolimus (Rapamycin, Rapamune), a potent
      immunosuppressant used to prevent rejection of transplanted kidneys, has also
      proven effective at inhibiting restenosis in humans when eluted from implanted
      stents. The aim of this study was to evaluate the effect of sirolimus treatment
      on the development of atherosclerosis in the aortic arch of apo E-/- mice fed a
      high-fat (Western) diet. Following 12 weeks of treatment with sirolimus (4
      mg/kg/d), the cholesterol content of the arch was reduced by 36% compared to
      untreated control mice fed the Western diet only. Although the murine model is
      not comparable to the human situation, the results of this study suggest that
      sirolimus may exert beneficial effects on atherosclerosis in transplant patients.

PMID- 14697998
TI  - Cyclosporine enhances vasorelaxation in coronary but not pulmonary artery after
      16-hour preservation with UW solution.
AB  - Cyclosporine (CsA), a calcineurin inhibitor, has been associated with endothelial
      dysfunction in transplant patients. Human and in vitro studies suggest that CsA
      produces endothelial dysfunction by impairing vascular endothelium-dependent
      relaxation. However, little is know about the CsA effects to modulate the
      vasorelaxation after prolonged graft preservation. In this study using a protocol
      designed to eliminate the influences of infusion pressure and shear stress, we
      evaluated the effect of CsA on vasorelaxation of coronary and pulmonary arteries
      after 16-hour University of Wisconsin (UW) solution preservation.

PMID- 14697999
TI  - Development and evaluation of an experimental model for investigating the
      pathogenesis and therapeutic strategies of acute liver failure.
AB  - Because of the various etiologies of acute liver failure (ALF) a clinically
      relevant model must fulfill four criteria--reversibility, reproducibility, ALF
      induced death, and a sufficient time interval for diagnosis and therapy between
      induction and death. In this study an experimental model was evaluated for these
      criteria. A total of 49 rats were randomized into seven groups: First, a pilot
      study was performed regarding the survival rate after different treatments: In
      group I, animals underwent a 70% liver resection. In group II, 70% liver
      resection was combined with ascending doses of postoperative endotoxin
      administration up to 400 microg/kg (group IIc). In group III, animals only
      underwent liver mobilization. In group IV, ALF was induced according to the
      protocol of group IIc, but with additional treatment of an endothelin-A-receptor
      (ETAR) antagonist. Animals in group V received only 400 microg endotoxin. After
      induction of ALF, all animals died within the first day, showing significantly
      elevated bilirubin and ammonium levels and severe damage to hepatocellular
      integrity. Application of the ETAR antagonist resulted in the survival of 6/7
      animals until the 14th day; the biochemical and histomorphological changes were
      reversible. All other animals survived to the 14th day. A clinically relevant
      model of ALF in rats can be created by the combination of 70% liver resection and
      endotoxin application to produce an inflammatory component.

PMID- 14698001
TI  - Break of tolerance via donor-specific blood transfusion by high doses of
      steroids: a differential effect after intestinal transplantation and heart
      transplantation.
AB  - Tolerance requires active mechanisms. How immunosuppressors affects tolerance is
      poorly understood. METHODS: RA (RT1(p))/PVG (RT1(c)) rats were used as
      donor/recipient. Intestinal and heart transplant model were selected as highly
      and poorly immunogenic organs. Studied groups were 1, rejecting control; 2,
      received peritransplant steroids; 3, donor-specific blood transfusion (DSBT); 4,
      DSBT plus peritransplant steroids; and 5, DSBT+periDSBT Ste. RESULTS: Intestinal
      transplant recipients in group 1 died on posttransplant day (d) 18. In group 2,
      steroids did not change survival (17 days, P >.05 versus group 1). With DSBT
      (group 3), all rats survived >75 days, whereas with steroids those in group 4
      survived 59 days (P >.05 vs group 3) and group 5 survived 51 days (P <.05 versus
      group 3). Survivors in group 2 were tolerant as evidenced by acceptance of
      secondary donor-specific (not third-party) graft. However, 100% and 33% of donor
      specific secondary grafts were rejected in groups 4 and 5 (P <.05 and P >.05
      versus group 3). In heart transplants, steroid treatment had no effect on graft
      survival (group 1 9 days; group 2 9 days; P >.05). DSBT (group 3) induced 100%
      tolerance (primary: >100 days, secondary: 100%). Unlike in intestinal
      transplantation, adjunction peritransplant steroids (group 4) allowed 100% of
      primary and 83% of secondary graft acceptance (P >.05 versus group 3). In group
      5, (DSBT+periDSBT steroids) acceptance of primary and secondary grafts tended to
      be reduced (primary: 77 days; P >.05 versus group 3; secondary: 67%, P >.05
      versus group 3). CONCLUSION: Steroid induction did not prolong graft survival
      after either intestinal or heart transplant. Adjunction of steroids to a DSBT
      tolerogenic regimen caused rejection of primary and secondary grafts,
      particularly after intestinal transplantation. Routine use of steroids in the
      clinics must be reconsidered, particularly when immunogenic organs are
      transplanted and when immunomodulation is applied.

PMID- 14698000
TI  - Time frame of pancreas allograft rejection: an immunogenetic analysis in MHC
      disparate, presensitized inbred rat strains.
AB  - AIM: The pattern of rejection of vascularized pancreas allografts in
      presensitized recipients was studied among congeneic and recombinant rat strains
      in order to establish the time frame of rejection. Donors and recipients differed
      either in their entire MHC or in class I or class II MHC antigens. MATERIAL AND
      METHODS: Streptozotocin diabetic (55 mg/kg bone weight) recipients underwent an
      intra-abdominal heterotopic pancreas whole organ transplantation. The exocrine
      secretion of the pancreas was suppressed by ligation of the duct. Rejection was
      defined as recurrence of diabetic hyperglycemia exceeding 14 mmol/L, which was
      subsequently confirmed by histologic examination. The pancreas recipients were
      presensitized by repetitive donor-specific skin transplants performed 12, 8, and
      4 weeks prior to pancreas grafting. RESULTS: The results shown accelerated
      rejection in all instances. Animals with incompatibility for the entire MHC
      showed a median rejection time in naive recipients of 12.5 days and in
      presensitized recipients of 8 days. Class I MHC incompatible native recipients
      rejected the allografts after 16.5 days (median) and presensitized recipients
      after 9 days (median). Concerning class II MHC incompatibility rejection appeared
      in naive recipients after 16 days (median) and in presensitized recipients after
      7 days (median). Hyperacute rejection, however, was not observed. DISCUSSION:
      These results show an accelerated pattern of rejection in all instances caused by
      donor MHC antigens. Hyperacute rejection, however, was not observed. The effect
      is slightly pronounced in class II MHC incompatibility. Acceleration of rejection
      may be caused by stimulation of the humoral as well as the cellular pathway of
      the immune response. The underlying mechanisms concerning the different MHC
      incompatibilities, however, remain speculative.

PMID- 14698002
TI  - Low-dose donor bone marrow cells and splenocytes plus adenovirus encoding for
      CTLA4Ig gene promote stable mixed chimerism and long-term survival of rat cardiac
      allografts.
AB  - Co-stimulatory blockade combined with donor bone marrow transfusion engenders
      stable mixed chimerism and robust tolerance to various organ and cell
      transplants. However, repeated administration of costly agents to block the co
      stimulatory pathway and the high doses of donor bone marrow cells (BMCs) used in
      most protocols are impeding clinical development of this strategy. To circumvent
      these shortcomings, we developed a plan in which repeated administration of
      costly agents was replaced by a single injection of adenovirus containing the
      gene of interest, and the high dose of donor BMCs replaced by a mixture of low
      dose donor BMCs and splenocytes (SPLCs). Cardiac allografts from DA(RT-1(a)) rats
      were transplanted heterotopically into the abdomens of LEW(RT-1(1)) rats. A
      cocktail of adenovirus containing CTLA4Ig gene (AdCTLA4Ig), donor BMCs (100 x
      10(6)), and SPLCs (50 x 10(6)) was administered to recipients via the portal vein
      immediately after grafting (n = 6). Treatment with regimens, including AdCTLA4Ig
      only, AdCTLA4Ig plus donor BMCs, and AdCTLA4Ig plus donor SPLCs, significantly
      prolonged cardiac allograft survival in recipient rats, while animals that
      received no treatment or treatment with control adenovirus (AdLacZ) promptly
      rejected their allografts. Nevertheless, LEW recipients treated with AdCTLA4Ig
      and the mixture of a low dose of donor BMCs and SPLCs developed stable mixed
      chimerism, rendering them long-term survivors of cardiac allografts that also
      accepted skin grafts from the donor but not the third-party strain. We conclude
      that blockade of CD28-B7 pathway with AdCTLA4Ig plus a mixture of low doses of
      donor BMCs and SPLCs is a feasible strategy to induce long-term mixed chimerism
      with a potential application for clinical development.

PMID- 14698003
TI  - Prolonged retention of vaccinia virus complement control protein following IP
      injection: implications in blocking xenorejection.
AB  - The vaccinia virus complement control protein (VCP) blocks classic and alternate
      complement pathways by binding to the third and fourth complement components and
      by blocking the formation of the C3-convertase as well as by accelerating the
      decay of the C3 and C4 convertase. The therapeutic potential of VCP has been
      extensively studied for brain injury, xenotransplantation, Alzheimer's disease,
      and spinal cord injury. We investigated the pharmacokinetic behavior of rVCP in
      mice. Dosage of rVCP was studied by injecting different concentrations of rVCP. A
      25 mg/kg or greater dose injected intraperitoneally was found to be adequate to
      suppress complement for more than 8 hours.

PMID- 14698004
TI  - Bicistronic adenovirus-mediated gene transfer of CTLA4Ig gene and CD40Ig gene
      result in indefinite survival of islet xenograft.
AB  - Blockade of CD40-CD154 costimulatory pathway in mice and primates with anti-CD154
      monoclonal antibodies results in prolonged survival of vascularized organs and
      islet grafts. CD40Ig, a recombinant fusion protein comprised of the extracellular
      domain of human CD40 molecule in frame fused with the site-mutated human IgG1 Fc
      region, abrogated the cognate interaction of CD40-CD154 pathway by binding the
      CD154 molecule. In this study, replication-defective adenovirus containing the
      CD40Ig gene was prepared by homologous recombination and used to infect freshly
      isolated islets from LEW rats (RT-1(1)) in vitro using a titered dose. The islet
      transfectants (500 per recipient) were transplanted under the left kidney capsule
      of streptozocin-rendered diabetic C57BL/6 mouse recipient (H-2(b)). The mean
      survival time of AdCD40Ig-transfected islet grafts was significantly prolonged,
      while mock-infected grafts and AdEGFP-transfected grafts were rejected in normal
      fashion. Additionally, dose-dependent prolongation of islet graft survival was
      observed in mice receiving AdCD40Ig-transfected grafts. In conclusion, local
      production of Cd40Ig via adenoviral-mediated gene transfer induced dose-dependent
      prolongation of LEW --> Balb-c islet xenografts.

PMID- 14698005
TI  - Individual differences in the response to ingested nutrients.

PMID- 14698006
TI  - Nutrigenomics: unraveling man's constitution in relation to food.

PMID- 14698007
TI  - Nutrigenomics: exploiting systems biology in the nutrition and health arenas.

PMID- 14698008
TI  - Genome scans for human nutritional traits: what have we learned?

PMID- 14698009
TI  - Application of genomic technologies: DNA microarrays and metabolic profiling of
      obesity in the hypothalamus and in subcutaneous fat.

PMID- 14698010
TI  - Diet-disease gene interactions.

PMID- 14698011
TI  - Gene and bacterial identification using high-throughput technologies: genomics,
      proteomics, and phonemics.

PMID- 14698012
TI  - Targeting autoimmune diseases through nutraceuticals.

PMID- 14698013
TI  - Genetic variations and inflammation: a practical nutrigenomics opportunity.

PMID- 14698014
TI  - Applications of microarray and bioinformatics tools to dissect molecular
      responses of the central nervous system to antioxidant micronutrients.

PMID- 14698015
TI  - Chromatin effects in nutrition, cancer, and obesity.

PMID- 14698016
TI  - Early nutrition, epigenetic changes at transposons and imprinted genes, and
      enhanced susceptibility to adult chronic diseases.

PMID- 14698017
TI  - Reporting of model validation procedures in human studies of genetic
      interactions.

PMID- 14698018
TI  - Epistasis among genes is a universal phenomenon in obesity: evidence from rodent
      models.

PMID- 14698019
TI  - Elucidating the role of nutraceuticals in overexpressing antiapoptotic proteins
      in prostate cancer.

PMID- 14698020
TI  - Activation of MAP kinases, apoptosis and nutrigenomics of gene expression
      elicited by dietary cancer-prevention compounds.

PMID- 14698021
TI  - Cancer prevention by food factors through targeting signal transduction pathways.

PMID- 14698022
TI  - Nutraceuticals, apoptosis, and disease prevention.

PMID- 14698023
TI  - Nutrigenomic approach to understanding the mechanisms by which dietary long-chain
      fatty acids induce gene signals and control mechanisms involved in
      carcinogenesis.

PMID- 14698024
TI  - Identification of candidate genes involved in the regulation of adipocyte
      differentiation using microarray-based gene expression profiling.

PMID- 14698025
TI  - Gene expression profiling of adipose tissue: individual, depot-dependent, and sex
      dependent variabilities.

PMID- 14698026
TI  - Genetically modified mouse models for disorders of fatty acid metabolism:
      pursuing the nutrigenomics of insulin resistance and type 2 diabetes.

PMID- 14698027
TI  - Genetic architecture of ingestive behavior in humans.

PMID- 14698028
TI  - Microarray gene expression profiling in obesity and insulin resistance.

PMID- 14698030
TI  - Genetic variation and statistical considerations in relation to overfeeding and
      underfeeding in humans.

PMID- 14698029
TI  - Role of UCP2 and UCP3 in nutrition and obesity.

PMID- 14698031
TI  - Proteomics and mass spectrometry in nutrition research.

PMID- 14698032
TI  - Nutritional genomics in yeast models.

PMID- 14698033
TI  - Nuclear receptor signaling in macrophages.
AB  - Macrophages play diverse roles in host defense and in maintenance of homeostasis.
      Based on their ability to promote inflammatory responses, inappropriate
      macrophage function also contributes to numerous pathological processes,
      including atherosclerosis, rheumatoid arthritis and inflammatory bowel disease.
      Members of the nuclear receptor superfamily of ligand-dependent transcriptions
      factors have emerged as key regulators of inflammation and lipid homeostasis in
      macrophages. These include the glucocorticoid receptor (GR), which inhibits
      inflammatory programs of gene expression in response to natural corticosteroids
      and synthetic anti-inflammatory ligands such as dexamethasone. Also, in response
      to endogenous eicosanoids and oxysterols, respectively, peroxisome proliferator
      activated receptors (PPARs) and liver X receptors (LXRs) regulate transcriptional
      programs involved in inflammatory responses and lipid homeostasis. Identification
      of their mechanisms of action should help guide the development of new
      therapeutic agents useful in the treatment of diseases in which macrophages play
      critical pathogenic roles.

PMID- 14698034
TI  - Opposite regulation of the rat and human cytosolic aspartate aminotransferase
      genes by fibrates.
AB  - Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARalpha)
      activator, increases the expression of the cytosolic aspartate aminotransferase
      (cAspAT) gene in human liver cells, which may partially explain the increase of
      this enzyme in the serum of individuals undergoing fenofibrate treatment.
      Conversely, in rodents, fenofibrate represses the expression of the cAspAT gene.
      We compared the mechanisms of fenofibrate action in human and rat hepatoma cells.
      Transfection assays of the wild-type and mutated rat promoters in Fao and H4IIEC3
      cells established a critical role for sequences similar to nuclear receptor
      responsive elements in the -404/-366 bp region. Nuclear proteins bound to these
      sequences and the amounts of protein bound were decreased by fenofibrate
      treatment, probably accounting for the decreased gene expression. Pharmacological
      studies confirmed the involvement of PPARalpha. However, this receptor did not
      bind directly to these sequences. The human promoter was cloned and the
      regulatory region localized between -2663/-706 bp. Co-transfection assays
      suggested that, in humans, the PPARalpha was also involved in the increase in
      expression of the cAspAT gene due to fibrates, without the presence of a
      canonical PPAR responsive element.

PMID- 14698035
TI  - A new structural class of proteasome inhibitors identified by microbial screening
      using yeast-based assay.
AB  - A yeast-based growth interference assay was developed utilizing a yeast strain in
      which expression of Xenopus cyclin A1 was induced to elevate cell division cycle
      28 (Cdc28) kinase activity. Since the hyperactivation of Cdc28 kinase in yeast
      results in a growth-arrest phenotype, compounds which could rescue the cyclin A1
      induced growth arrest might be potential new, antitumor drug candidates acting on
      the cyclin-dependent, kinase-mediated, cell cycle regulation pathway. In the
      course of our microbial screening program, the new Streptomyces metabolites,
      belactosins, were identified. As reported previously, belactosin A induced cell
      cycle arrest at G2/M phase in human cancer cells. However, the molecular
      mechanism of action was unknown. We herein demonstrate the proteasome inhibition
      by belactosin A. Belactosin A did not inhibit yeast Cdc28 kinase and human cyclin
      dependent kinase in vitro. On the other hand, it inhibited the chymotrypsin-like
      activity of the rabbit 20S proteasome. From the initial SAR studies, we
      identified a hydrophobic belactosin A derivative, KF33955, which exhibited a 100
      fold greater growth-inhibitory activity against HeLa S3 cells than belactosin A,
      presumably due to its higher cell permeability. The biochemical analysis using
      KF33955 suggested that the proteasome inhibitory activity of KF33955 were
      irreversible and required the beta-lactone moiety to inhibit the proteasome.
      KF33955 increased the intracellular levels of protein ubiquitination in NIH3T3
      cells. In addition, KF33955 treatment resulted in the accumulation of known
      proteasome substrates in HeLa S3 cells. These results identify belactosin A as a
      useful lead compound to target proteasome for the treatment of disease whose
      etiology is dependent on the unregulated ubiquitin-proteasome pathway.

PMID- 14698036
TI  - Cytochrome P450 dependent metabolism of the new designer drug 1-(3
      trifluoromethylphenyl)piperazine (TFMPP). In vivo studies in Wistar and Dark
      Agouti rats as well as in vitro studies in human liver microsomes.
AB  - 1-(3-Trifluoromethylphenyl)piperazine (TFMPP) is a designer drug with
      serotonergic properties. Previous studies with male Wistar rats (WI) had shown,
      that TFMPP was metabolized mainly by aromatic hydroxylation. In the current
      study, it was examined whether this reaction may be catalyzed by cytochrome P450
      (CYP)2D6 by comparing TFMPP vs. hydroxy TFMPP ratios in urine from female Dark
      Agouti rats, a model of the human CYP2D6 poor metabolizer phenotype (PM), male
      Dark Agouti rats, an intermediate model, and WI, a model of the human CYP2D6
      extensive metabolizer phenotype. Furthermore, the human hepatic CYPs involved in
      TFMPP hydroxylation were identified using cDNA-expressed CYPs and human liver
      microsomes. Finally, TFMPP plasma levels in the above mentioned rats were
      compared. The urine studies suggested that TFMPP hydroxylation might be catalyzed
      by CYP2D6 in humans. Studies using human CYPs showed that CYP1A2, CYP2D6 and
      CYP3A4 catalyzed TFMPP hydroxylation, with CYP2D6 being the most important enzyme
      accounting for about 81% of the net intrinsic clearance, calculated using the
      relative activity factor approach. The hydroxylation was significantly inhibited
      by quinidine (77%) and metabolite formation in poor metabolizer genotype human
      liver microsomes was significantly lower (63%) compared to pooled human liver
      microsomes. Analysis of the plasma samples showed that female Dark Agouti rats
      exhibited significantly higher TFMPP plasma levels compared to those of male Dark
      Agouti rats and WI. Furthermore, pretreatment of WI with the CYP2D inhibitor
      quinine resulted in significantly higher TFMPP plasma levels. In conclusion, the
      presented data give hints for possible differences in pharmacokinetics in human
      PM and human CYP2D6 extensive metabolizer phenotype subjects relevant for risk
      assessment.

PMID- 14698037
TI  - COX-2-mediated PGD2 synthesis regulates phosphatidylcholine biosynthesis in rat
      renal papillary tissue.
AB  - Phosphatidylcholine (PC) is the major membrane phospholipid in mammalian cells.
      Previous works from our laboratory demonstrated a close metabolic relationship
      between the maintenance of PC biosynthesis and the prostaglandins endogenously
      synthesized by cyclooxygenase (COX) in rat renal papilla. In the present work, we
      studied the COX isoform involved in papillary PC biosynthesis regulation. The
      incorporation of [methyl-3H]choline and [32P]orthophosphate to PC was determined
      in the absence and presence of SC-560 and NS-398, COX-1 and COX-2 specific
      inhibitors. PC synthesis was highly sensitive to COX-2 inhibition, while COX-1
      inhibition only reduced PC synthesis at high SC-560 concentration. The analysis
      of choline-containing metabolites showed that COX-2 inhibition affected the
      formation of CDP-choline intermediary. The evaluation of PC biosynthetic enzymes
      revealed that microsomal, as well as nuclear, CTP:phosphocholine
      cytidylyltransferase (CCT), and nuclear-CDP-choline:1,2-diacylglycerol
      cholinephosphotransferase (CTP) activities were affected by COX-2 inhibition. The
      addition of exogenous prostaglandin D(2) (PGD(2)) restored nuclear-CCT and -CPT
      activities but not microsomal CCT. Papillary synthesis of PGD(2) was only
      detected in nuclear fraction where it was blocked by COX-2 inhibitor NS-398, but
      not by COX-1 inhibitor. All together, the present results demonstrated that COX-2
      mediated PGD(2) synthesis is a PC biosynthesis regulator in rat renal papilla.
      Considering the importance of the maintenance of PC biosynthesis for the
      preservation of cell membrane homeostasis to ensure cell viability, and the
      extensive use of COX-2 inhibitors in therapeutics, the present results could have
      great pharmacological implications, and can constitute a biochemical explanation
      for the nephrotoxic effect of non-steroidal anti-inflammatory drugs.

PMID- 14698038
TI  - Indinavir alters sterol and fatty acid homeostatic mechanisms in primary rat
      hepatocytes by increasing levels of activated sterol regulatory element-binding
      proteins and decreasing cholesterol 7alpha-hydroxylase mRNA levels.
AB  - Human immunodeficiency virus protease inhibitors induce hyperlipidemia in many
      patients treated with these drugs. We examined the effects of indinavir on
      cholesterol and bile acid homeostatic mechanisms in a primary rat hepatocyte
      (PRH) culture model. In PRH, indinavir up-regulated (2.5-fold) 3-hydroxy-3
      methylglutaryl-Coenzyme A reductase mRNA levels 24hr after drug addition. In
      these same experiments, cholesterol 7alpha-hydroxylase (CYP7A1) mRNA levels, the
      rate-limiting enzyme in bile acid biosynthesis, was decreased up to 10-fold.
      Fatty acid synthase mRNA levels were up-regulated more than 3-fold under these
      conditions. Indinavir did not alter CYP7A1 transcriptional activity, but
      decreased CYP7A1 mRNA half-life in PRH from 1.5hr to less than 0.5hr. Sterol
      regulatory element-binding protein-1 (SREBP-1) mature form was increased
      approximately 6-fold by this drug. Indinavir-induced mRNA changes and SREBP-1
      mature protein levels were significantly abated by the addition of cholesterol,
      solubilized in beta-cyclodextrin, to culture medium. Indinavir markedly decreased
      endogenous cholesterol esterification and increased cholesterol in intracellular
      membranes in primary hepatocytes. Indinavir gavaged into intact mice also
      markedly increased SREBP-1 and SREBP-2 (mature forms) in hepatic nuclei. CYP7A1
      mRNA was also decreased approximately 52% in indinavir-treated animals. We
      propose that indinavir disrupts cellular cholesterol homeostasis by increasing
      SREBP's and decreasing CYP7A1 mRNA.

PMID- 14698039
TI  - Variable modulation of opioid brain uptake by P-glycoprotein in mice.
AB  - The efflux transporter P-glycoprotein (P-gp) is an important component of the
      blood-brain barrier (BBB) that limits accumulation of many compounds in brain.
      Some opioids have been shown to interact with P-gp in vitro and in vivo. Genetic
      or chemical disruption of P-gp has been shown to enhance the antinociceptive
      and/or toxic effects of some opioids, although the extent of this phenomenon has
      yet to be understood. The purpose of this study was to assess quantitatively the
      influence of mdr1a P-gp on initial brain uptake of chemically diverse opioids in
      mice. The brain uptake of opioids selective for the mu (fentanyl, loperamide,
      meperidine, methadone, and morphine), delta (deltorphin II, DPDPE, naltrindole,
      SNC 121) and kappa (bremazocine and U-69593) receptor subtypes was determined in
      P-gp-competent (wild-type) and P-gp-deficient [mdr1a(-/-)] mice with an in situ
      brain perfusion model. BBB permeability of the opioids varied by several orders
      of magnitude in both mouse strains. The difference in brain uptake between P-gp
      competent and P-gp-deficient mice ranged from no detectable effect (meperidine)
      to >/=8-fold increase in uptake (DPDPE, loperamide, and SNC 121). In addition,
      loperamide efflux at the BBB was inhibited by quinidine. These results
      demonstrate that P-gp modulation of opioid brain uptake varies substantially
      within this class of compounds, regardless of receptor subtype. P-gp-mediated
      efflux of opioids at the BBB may influence the onset, magnitude, and duration of
      analgesic response. The variable influence of P-gp on opioid brain distribution
      may be an important issue in the context of pharmacologic pain control and drug
      interactions.

PMID- 14698040
TI  - Effect of vascular endothelial growth factor and epidermal growth factor on
      iatrogenic apoptosis in human endothelial cells.
AB  - To study the effect of growth factors on iatrogenic apoptosis, we examined the
      influence of vascular endothelial growth factor (VEGF) and epidermal growth
      factor (EGF) on staurosporine-induced apoptosis in primary cultures of human
      umbilical vein endothelial cells (HUVEC). Apoptosis was evaluated by a cell
      viability test, the TUNEL-POD assay and the activation of the pro-apoptotic
      caspase-3. Staurosporine (10-100nM) caused the activation of caspase-3. This
      effect was manifest after 2hr of incubation and reached its maximum after 5hr.
      Severe loss of viability followed within 18hr. VEGF or EGF (10-100ng/mL) added
      together with staurosporine decreased the activation of caspase-3. The loss of
      viability was 24hr delayed. The action of growth factors was observed at 1% serum
      concentration but also at concentration optimal for HUVEC survival (10%, v/v).
      Furthermore, the inhibition of PI-3 kinase (PI-3K) by wortmannin or LY294002 as
      well as the inhibition of MEK by PD098059 or U0126 prevented the protective
      effect of VEGF and EGF. Western blotting analysis showed that after 3hr of
      incubation with staurosporine the level of the anti-apoptotic protein Mcl-1
      decreased and this effect was reverted by VEGF. It is concluded that VEGF and EGF
      antagonize the pro-apoptotic action of staurosporine by the combined signalling
      of PI-3K and ERKs pathways.

PMID- 14698041
TI  - Influence of lipid lowering fibrates on P-glycoprotein activity in vitro.
AB  - Statin/fibrate combinations are frequently used to treat mixed dyslipidemia.
      However, these combinations may cause life-threatening drug interactions (e.g.
      rhabdomyolysis) possibly induced by modifications of cytochrome P450 isozyme
      activities. Some statins are also transported by P-glycoprotein (Pgp) and may act
      as inhibitors of this drug efflux pump. So far, nothing is known about possible
      Pgp modulating effects of fibrates. We tested whether gemfibrozil, fenofibrate,
      fenofibric acid, and bezafibrate inhibit Pgp in vitro using a calcein
      acetoxymethylester (calcein-AM) uptake assay and confocal laser scanning
      microscopy with bodipy-verapamil as substrate in L-MDR1 cells, which overexpress
      human Pgp. In uptake assays in cells with (L-MDR1) and without (LLC-PK1) human
      Pgp we also investigated whether these compounds are transported by Pgp.
      Intracellular concentrations were measured by liquid chromatography tandem mass
      spectrometry. Of the tested fibrates, only fenofibrate increased calcein-AM
      uptake into cells indicating an inhibition of Pgp mediated transport by this
      compound. The potency of fenofibrate (mean+/-SD: 7.1+/-3.2 microM), evaluated by
      calculating the concentration needed to double baseline fluorescence (f2), was
      similar to that of simvastatin (5.8+/-1.5 microM), lovastatin (10.1+/-1.0), and
      verapamil (4.7+/-0.8 microM). For simvastatin and fenofibrate Pgp inhibition was
      confirmed with confocal laser scanning microscopy. Fenofibrate, fenofibric acid,
      gemfibrozil, and bezafibrate showed no difference in the cellular uptake between
      LLC-PK1 and L-MDR1, indicating that the tested fibrates are not Pgp substrates.
      In conclusion, this study demonstrates that fenofibrate inhibits Pgp in vitro
      with a potency similar to simvastatin.

PMID- 14698042
TI  - Structure-activity relationships for substrate recognition by the human dopamine
      transporter.
AB  - Information is available on the structure-activity relationships for dopamine as
      a substrate for uptake by the dopamine transporter. However, dopamine transport
      is a complex process involving substrate binding, translocation, release as well
      as transporter reorientation. The present study examines only the substrate
      recognition step by assessment of the potency of various dopamine-related
      compounds in inhibiting the binding of the cocaine analog [3H]2beta-carbomethoxy
      3beta-(4-fluorophenyl)tropane ([3H]WIN 35,428) to human dopamine transporters
      expressed in HEK-293 cells. alpha-Methylation of the side chain, the presence of
      the amine, and the 2-carbon-length of the side chain were found to be important
      for binding affinity, whereas beta-hydroxylation of the side chain and
      methoxylation at the phenyl ring generated weaker compounds. In addition, the
      presence of both m- and p-OH at the phenyl ring bestowed an increase in potency
      but the presence of p-OH alone a decrease. N-alkylation (propylation or
      methylation) had little or an even slightly beneficial effect on affinity,
      whereas alpha-carbonylation and alpha-methanoylation reduced affinity. Amino
      naphthalene compounds with a fused benzenoid ring system retained some potency
      consonant with the extended (i.e. beta-rotameric) trans (=anti) form of the side
      chain in dopamine when interacting with the transporter. In a second series of
      experiments, the interaction between dopamine and structural variants was
      assessed by monitoring the capability of a compound to shift the dopamine
      inhibition curve to the right as expected for a competitive inhibitor acting at
      the same site. Appreciable deviation from competitive interaction was observed by
      removal of the amine from the side chain, by alpha-carbonylation, and by alpha
      methanoylation. Two blocker-type compounds, semi-rigid variants of cocaine, also
      displayed significant deviation. A substrate-based compound, inhibiting cocaine
      analog binding without interfering with dopamine recognition, could be a cocaine
      antagonist allowing conformational changes to occur during dopamine uptake.

PMID- 14698043
TI  - Statins upregulate CD36 expression in human monocytes, an effect strengthened
      when combined with PPAR-gamma ligands Putative contribution of Rho GTPases in
      statin-induced CD36 expression.
AB  - Scavenger receptor CD36 plays important roles in atherosclerosis, inflammation,
      thrombosis, and angiogenesis. Statins besides lowering serum cholesterol levels,
      exhibit a variety of effects on inflammation, coagulation and atherosclerosis
      lesion stability. PPAR-gamma ligands influence macrophage responses to many
      inflammatory stimuli. Herein, we investigated in human monocytes the effect of
      statins alone, and in combination with PPAR-gamma ligands on CD36 expression, as
      well as the molecular mechanisms underlying the regulatory action of statins. Our
      results demonstrate that statins upregulate both CD36 surface protein and mRNA by
      potentiating the transcription of the CD36 gene. Furthermore, the combination of
      statins and PPAR-gamma ligands has an additive effect on CD36 expression. Effects
      of statins on CD36 expression were prevented by mevalonate and geranylgeraniol,
      indicating the requirement of geranylgeranylated proteins for CD36 regulation.
      Rho GTPases inhibitor C3 exoenzyme reproduced the effect of statins, while Rho
      activator lysophosphatidic acid downregulated CD36. Transient expression of
      dominant-negative mutants of RhoA and RhoB induced a significant increased in
      CD36 promoter activity. Finally, the actin cytoskeleton disrupter cytochalasin D
      upregulated CD36. These data indicate that Rho proteins are important modulators
      of CD36 expression, and strongly suggest that statins increased CD36 expression
      by disrupting cytoskeleton organization by inactivating Rho GTPases. These
      features prompt to investigate the roles of Rho GTPases and actin cytoskeleton
      modulators on monocytic functions affected by statins.

PMID- 14698044
TI  - Disruption of mitochondria during tocotrienol-induced apoptosis in MDA-MB-231
      human breast cancer cells.
AB  - Tocotrienols, which are Vitamin E isoforms, are known to inhibit the growth of
      human breast cancer cells due partly to apoptosis. However, the characterization
      of tocotrienol-induced apoptosis is incomplete, particularly what happens during
      the initiation phase that precedes execution of the cells. The objective of this
      study was to clarify the apoptotic effects of tocotrienols, with especial
      emphasis in determining if the mitochondria-mediated death pathway is activated
      when human breast cancer cells are incubated with a specific tocotrienol isomer.
      During incubation with gamma-tocotrienol, MDA-MB-231 human breast cancer cells
      showed membrane blebbing, and apoptotic bodies were present. Upon 4',6-diamidino
      2-phenylindole staining of the cells, chromatin condensation and fragmentation
      were observed. Additionally, the annexin V-binding assay detected the
      translocation of membrane phospholipid during earlier analysis of the cells.
      Taken together, these results further establish that gamma-tocotrienol can induce
      apoptosis in human breast cancer cells. To help elucidate how gamma-tocotrienol
      induced the apoptosis, some important parameters related to the mitochondria
      mediated death pathway were examined next. In gamma-tocotrienol-treated cells,
      the mitochondria were disrupted. Collapse of the mitochondrial membrane potential
      was detected, and cytochrome c was released later from mitochondria. However,
      expression of Bax and Bcl-2 (mRNA and protein) did not change. Furthermore, poly
      (ADP-ribose)-polymerase cleavage was not detected, suggesting that caspases were
      not involved in the gamma-tocotrienol-induced apoptosis. These results imply that
      cytochrome c is not the critical protein released from mitochondria that triggers
      gamma-tocotrienol-induced apoptosis in MDA-MB-231 cells.

PMID- 14698046
TI  - Cell cycle arrest and autoschizis in a human bladder carcinoma cell line
      following Vitamin C and Vitamin K3 treatment.
AB  - Exponentially growing cultures of human bladder tumor cells (T24) were treated
      with Vitamin C (VC) alone, Vitamin K(3) (VK(3)) alone, or with a VC:VK(3)
      combination for 1, 2, or 4hr. Flow cytometry of T24 cells exposed to the vitamins
      for 1h revealed a growth arrested population and a population undergoing cell
      death. Cells in G(1) during vitamin treatment arrested in G(1) while those in S
      phase progressed through S phase and arrested in G(2)/M. DNA synthesis decreased
      to 14 to 21% of control levels which agreed with the percent of cells in S phase
      during treatment. Annexin V labeling demonstrated the majority of the cells died
      by autoschizis, but necrosis and apoptosis also were observed. Catalase treatment
      abrogated both cell cycle arrest and cell death which implicated hydrogen
      peroxide (H(2)O(2)) in these processes. Redox cycling of VC and VK(3) increased
      H(2)O(2) production and decreased cellular thiol levels and DNA content, while
      increasing intracellular Ca(2+) levels and lipid peroxidation. Feulgen staining
      of treated cells revealed a time-dependent decrease in tumor cell DNA, while
      electrophoresis revealed a spread pattern. These results suggest that Ca(2+)
      disregulation activates at least one DNase which degrades tumor cell DNA and
      induces tumor cell death.

PMID- 14698045
TI  - Potent, selective and cell-mediated inhibition of human herpesvirus 6 at an early
      stage of viral replication by the non-nucleoside compound CMV423.
AB  - CMV423 (2-chloro-3-pyridin-3-yl-5,6,7,8-tetrahydroindolizine-1-carboxamide) is a
      new antiviral agent with potent and selective in vitro activity against the beta
      herpesvirus human cytomegalovirus (HCMV), but not against alpha- or gamma
      herpesviruses. Here we report that its activity also extends to human herpesvirus
      6 (HHV-6) and 7 (HHV-7). When compared in vitro to ganciclovir and foscarnet (the
      standard drugs recommended for treatment of HHV-6 infections), CMV423 showed a
      superior selectivity, due to its high activity (antiviral IC(50): 53nM) and low
      cytotoxicity (CC(50): 144microM), both in continuous cell lines and in CBLCs
      infected with HHV-6. From mechanistic experiments at the level of viral mRNA and
      protein expression, we learned that CMV423 targets an event following viral entry
      but preceding viral DNA replication. Its antiviral action was dependent on the
      cell line used, implying involvement of a cellular component. When compared to a
      panel of known protein kinase inhibitors, CMV423 was found to share anti-HHV-6
      characteristics with herbimycin A, which affects tyrosine kinase activity through
      heat shock protein 90 (Hsp90) inhibition. We demonstrated that high
      concentrations of CMV423 have an inhibitory effect on the total cellular protein
      tyrosine kinase activity, and that CMV423 and herbimycin A, when combined, act
      synergistically against HHV-6. The activities of cyclin-dependent kinases,
      protein kinases A and C, and the HHV-6-encoded pU69 kinase were not affected. We,
      therefore, conclude that CMV423 exerts its activity against HHV-6 through
      inhibition of a cellular process that is critical at early stages of viral
      replication and that may affect protein tyrosine kinase activity.

PMID- 14698047
TI  - Evidence that activation of nuclear factor-kappaB is essential for the cytotoxic
      effects of doxorubicin and its analogues.
AB  - Several reports within the last 5 years have suggested that nuclear factor (NF)
      kappaB activation suppresses apoptosis through expression of anti-apoptotic
      genes. In the present report, we provide evidence from four independent lines
      that NF-kappaB activation is required for the cytotoxic effects of doxorubicin.
      We used doxorubicin and its structural analogues WP631 and WP744, to demonstrate
      that anthracyclines activate NF-kappaB, and this activation is essential for
      apoptosis in myeloid (KBM-5) and lymphoid (Jurkat) cells. All three
      anthracyclines had cytotoxic effects against KBM-5 cells; analogue WP744, was
      most potent, with an IC(50) of 0.5 microM, and doxorubicin was least active, with
      an IC(50) of 2 microM. We observed maximum NF-kappaB activation at 1 microM with
      WP744 and at 50 microM with doxorubicin and WP631, and this activation correlated
      with the IkappaBalpha degradation. Because the anthracycline analogue (WP744),
      most active as a cytotoxic agent, was also most active in inducing NF-kappaB
      activation and the latter preceded the cytotoxic effects, suggests that NF-kappaB
      activation may mediate cytotoxicity. Second, receptor-interacting protein
      deficient cells, which did not respond to doxorubicin-induced NF-kappaB
      activation, were also protected from the cytotoxic effects of all the three
      anthracyclines. Third, suppression of NF-kappaB activation by pyrrolidine
      dithiocarbamate, also suppressed the cytotoxic effects of anthracyclines. Fourth,
      suppression of NF-kappaB activation by NEMO-binding domain peptide, also
      suppressed the cytotoxic effects of the drug. Overall our results clearly
      demonstrate that NF-kappaB activation and IkappaBalpha degradation are early
      events activated by doxorubicin and its analogues and that they play a critical
      pro-apoptotic role.

PMID- 14698048
TI  - Novel N-thiolated beta-lactam antibiotics selectively induce apoptosis in human
      tumor and transformed, but not normal or nontransformed, cells.
AB  - Historically, it has been shown that the beta-lactam antibiotics play an
      essential role in treating bacterial infections while demonstrating selectivity
      for prokaryotic cells. We recently reported that certain N-methylthio-substituted
      beta-lactam antibiotics had DNA-damaging and apoptosis-inducing activities in
      various tumor cells. However, whether these compounds affect human normal or
      nontransformed cells was unknown. In the current study, we first show that a lead
      compound (lactam 1) selectively induces apoptosis in human leukemic Jurkat T, but
      not in the nontransformed, immortalized human natural killer (NK) cells.
      Additionally, we screened a library of other N-methylthiolated beta-lactams to
      determine their structure-activity relationships (SARs), and found lactam 12 to
      have the highest apoptosis-inducing activity against human leukemic Jurkat T
      cells, associated with increased DNA-damaging potency. Furthermore, we
      demonstrate that lactam 12, as well as lactam 1, potently inhibits colony
      formation of human prostate cancer cells. We also show that lactam 12 induces
      apoptosis in human breast, prostate, and head-and-neck cancer cells. Finally,
      lactam 12 induces apoptosis selectively in Jurkat T and simian virus 40
      transformed, but not in nontransformed NK and parental normal fibroblast, cells.
      Our results suggest that there is potential for developing this class of beta
      lactams into novel anticancer agents.

PMID- 14698049
TI  - Modulation of A1 adenosine receptor signaling by peroxynitrite.
AB  - Nitric oxide (NO) is a gaseous free radical involved in many pathophysiological
      processes. During oxidative stress, NO, its derivatives and adenosine are
      released. Considering adenosine neuroprotective role in the central nervous
      system (CNS) and toxicity of NO, we investigated the effect of a NO/peroxynitrite
      (ONOO(-)) donor, 3-morpholinosydnonimine (SIN-1), on A(1) adenosine receptor
      (A(1)AR) signaling pathway in rat cortical membranes. Membrane treatment with
      0.5mM SIN-1 for various periods of time (0-240min) decreased specific binding of
      the radiolabeled A(1)AR agonist, [3H]N(6)-cyclohexyladenosine ([3H]CHA), in a
      time-dependent manner, reaching the steady state after 120min. The inhibitory
      effect of SIN-1 was concentration-dependent, with an EC(50) value of 0.60+/
      0.30mM (N=3). Membrane pre-incubation with the superoxide anion (O(2)z.rad;(-))
      scavenger superoxide dismutase (SOD) followed by SIN-1 addition, abolished SIN-1
      inhibition of [3H]CHA binding. Membrane treatment with 0.5mM SIN-1 for 120min
      caused a significant 2-fold increase of the K(D) value for [3H]CHA without
      changing the B(max) value. Moreover, pre-incubation of membranes with A(1)AR
      agonists, CHA or N(6)-(2-phenylisopropyl)-adenosine (R-PIA) before SIN-1 addition
      increased the inhibitory effect while the selective A(1)AR antagonist, 8
      cyclopentyl-1,3-dipropylxanthine (DPCPX) had no activity. Membrane treatment with
      SIN-1 decreased receptor-stimulated guanosine 5'-O-(gamma[35S]thio)triphosphate
      ([35S]GTPgammaS) binding in a concentration-dependent manner. This treatment
      influenced [35S]GTPgammaS binding affinity for A(1)AR activated G(i) proteins in
      cortical membranes. These findings suggest that ONOO(-) modulates A(1)AR
      signaling pathways by affecting receptor G(i) protein coupling.

PMID- 14698050
TI  - Role of sodium in intracellular calcium elevation and leukotriene B4 formation by
      receptor-mediated activation of human neutrophils.
AB  - The role of Na(+) and Na(+) exchangers in intracellular Ca(2+) elevation and
      leukotriene B(4) (LTBs) formation was investigated in granulocyte macrophage
      colony-stimulating factor (GM-CSF)-primed, fMLP-stimulated human neutrophils.
      Isotonic substitution of extracellular Na(+) with N-methyl-D-glucamine(+)
      (NMDG(+)) resulted in over 85% inhibition of the LTBs generation observed (from
      14.1+/-0.9pmol/10(6) neutrophils to 1.7+/-1.0pmol/10(6) neutrophils at 0.3 microM
      fMLP). Isotonic substitution of Na(+) with NMDG(+) also induced a significant
      inhibition of fMLP-induced rise in cytosolic Ca(2+) concentration ([Ca(2+)](i))
      (from 2.17- to 0.78-fold increase over basal levels). Pretreatment with an
      inhibitor of the Na(+)/Ca(2+) exchanger (benzamil) did not inhibit either
      [Ca(2+)](i) rise or LTBs production, indicating that the observed effects of
      extracellular Na(+)-deprivation were unrelated to the Na(+)/Ca(2+) exchanger in
      receptor-mediated Ca(2+) influx, as previously hypothesized. LTBs production by
      thapsigargin-activated neutrophils was not affected by Na(+) depletion, but was
      totally abolished in the presence of EGTA, suggesting that store depletion-driven
      extracellular Ca(2+) influx is required for leukotriene synthesis and that this
      process is independent of Na(+)-deprivation. Exposure to Na(+)-free medium for
      the time of GM-CSF priming led to a significant decrease of intracellular pH
      values, suggesting a role of the Na(+)/H(+) exchanger in intracellular Na(+)
      depletion. Reducing the time of Na(+)-deprivation totally reversed the observed
      effect on LTBs production, resulting in enhanced, rather than inhibited,
      formation of LTBs. These results indicate that LTBs generation and [Ca(2+)](i)
      rise in human neutrophils primed by GM-CSF and stimulated with fMLP is dependent
      on intracellular Na(+) concentration, and, at variance with previously published
      results, unrelated to the Ca(2+) influx through the Na(+)/Ca(2+) exchanger.

PMID- 14698052
TI  - Epidemiology of Tritrichomonas foetus in beef bull populations in Florida.
AB  - The objectives of this study were to estimate the prevalence of herd and
      individual bull infection with Tritrichomonas foetus in a survey of beef bulls in
      the state of Florida and to perform an epidemiological investigation of risk
      factors for the disease. Bulls were tested for T. foetus colonization by a single
      preputial scraping and culture. Bull infection prevalence within herds was
      calculated and relationships with bull, herd factors, and production measurements
      were determined. The survey included 1984 beef bulls in 59 herds throughout
      Florida; nine bulls in three small herds (<100 cows) were later excluded from the
      models. An overall prevalence for T. foetus-infected bulls was 6.0% (within-herd
      prevalence ranged from 0 to 27%). The herd prevalence was 30.4% (i.e. at least
      one infected bull); infected bulls were found in 11.1 and 39.5% of herds sampled
      in North and South Florida, respectively. The likelihood of disease was greatest
      in larger herds in more extensive management settings (> or = 500 cows, 53.9%
      prevalence; medium-sized herds of 100-499 cows, 10.0% prevalence). Tritrichomonas
      foetus infection was associated with several bull factors, including age, breed,
      herd, and herd management practices (bull-to-cow ratio, bulls per breeding
      group). Tritrichomonas foetus infection continues to be prevalent in beef herds
      in Florida that use natural service.

PMID- 14698053
TI  - Risk factors and reproductive disorders associated with canine herpesvirus-1 (CHV
      1).
AB  - Canine herpesvirus-1 (CHV-1) is presumed to be enzootic in the dog population and
      is associated with fertility disorders and neonatal mortality. In this study we
      screened for risk factors affecting CHV-1 antibody titers and investigated the
      association between antibody titers and reproductive disorders. Therefore, serum
      from 545 dogs used for reproduction was analysed with an ELISA. Using a forward
      stepwise procedure and retaining significant risk factors (P<0.05), best fitting
      multifactorial generalized linear model (glm) procedures were built for males and
      females. The effect of antibody titers on reproductive disorders was analysed
      with logistic regression analysis. The association between reproductive disorders
      and seroprevalence was analysed in chi-square analyses using contingency tables.
      In both sexes, kennel cough and breeding management were found to have an impact
      on the CHV-1 antibody titer. Also, the influence of kennel cough on the antibody
      titer was correlated to the hygienic status of the kennel. In females, age,
      kennel size and cycle stage had an effect on CHV-1 antibody titers. Furthermore,
      kennel size and hygiene were found to be correlated. In males, mating experience
      had an impact on CHV-1 antibody titers. An association was observed between
      serological status and a history of abortion in bitches. In conclusion, this
      study suggests CHV-1 antibody titers may be affected by many factors, both on an
      environmental and host level. Therefore, interpretation of the serological status
      requires precaution. Furthermore, oronasal and venereal transmission seem to play
      a role in the spreading of infection.

PMID- 14698054
TI  - Resumption of postpartum ovarian cyclicity in high-producing Holstein cows.
AB  - The objective of this study was to investigate the resumption of ovarian
      cyclicity postpartum in high-producing dairy cows in commercial dairy farms under
      subtropical conditions. The cows were kept in a free-stall or tie-stall barn.
      Milk samples were collected from cows twice weekly, and progesterone in the skim
      milk was assayed by double-antibody ELISA. Cows were examined rectally and
      vaginoscopically at 2-week intervals after calving. Body condition score (BCS)
      and body weights were taken before and after calving. A cow was considered to
      have resumed ovarian cyclicity on the day of ovulation if followed by regular
      ovarian cycles. Thirty seven percent (n=20/54) of the cows had normal resumption
      of ovarian cyclicity (resumption within 45 days after calving), and 63% (n=34/54)
      had delayed resumption (resumption did not occur until >45 days after calving).
      Delayed resumption Type I (one or more ovarian cycles with luteal phase >20 days,
      i.e. prolonged luteal phase; 31.5%) and delayed resumption Type II (first
      ovulation did not occur until > or =45 days after calving, i.e. delayed first
      ovulation; 24.1%) were the most common types of delayed resumptions. Almost half
      (46.3%) of the cows did not resume their ovarian cyclicity until >65 days
      postpartum. Cows with delayed resumption Type I had a higher incidence of
      abnormal cervico-vaginal discharge (64.7%) and incomplete uterine involution
      (94.1%) compared to cows with normal resumption (P<0.01). The BCS of cows with
      delayed resumption Type II were lower than those of normal resumption cows at 5
      weeks and later in the postpartum period (P<0.05). Approximately two-thirds of
      high-producing cows had delayed resumption of ovarian cyclicity postpartum.
      Prolonged luteal phase and delayed first ovulation were two important ovarian
      dysfunctions that delayed postpartum resumption of cyclicity in high-producing
      dairy cows.

PMID- 14698055
TI  - Effects of feeding endophyte-infected fescue seed on reproductive traits of male
      mice divergently selected for resistance or susceptibility to fescue toxicosis.
AB  - Our objective was to determine whether consumption of endophyte-infected fescue
      seed affected male reproduction differently in a mouse line previously selected
      for susceptibility (S) to fescue toxicosis than in a line previously selected for
      fescue toxicosis resistance (R). For 8 weeks following weaning, 48 males per line
      were provided diets containing 50% of either endophyte-infected (E+) or endophyte
      free (E-) fescue seed. Each male was then paired with a female for 1 week, with
      litter size and weight recorded from subsequent births. Males were then killed,
      testes and seminal vesicles were weighed, cauda epididymal sperm were collected
      and testis cross-sections were fixed. The E+ diet reduced litter size by 0.5 in
      mates of S males but increased it by 1.0 in mates of R males (line by diet
      interaction P=0.05). Testis traits were not affected by diet or the line by diet
      interaction. Sperm integrity was adversely affected by the E+ diet (P<0.01) but
      did not differ significantly between lines, nor were line by diet interactions
      important. In earlier work, the E+ diet reduced long-term reproduction by a
      larger amount in S- than in R-line mated pairs. Because the E+ diet had similar
      effects on reproductive traits in R and S males in the current experiment, we
      infer that the differential impact previously reported acted primarily through
      traits expressed in females.

PMID- 14698056
TI  - Follicular activity and hormonal secretory profile in vicuna (Vicugna vicugna).
AB  - The objective of the present study was to characterize ovarian activity in non
      mated vicunas, relating ovarian structures (evaluated by transrectal
      ultrasonography, daily for 30 days) to changes in plasma concentrations of
      estradiol-17beta and progesterone. Ovarian follicular activity occurred in waves,
      characterized by the follicle emergence, growth and regression. The mean duration
      of follicular waves was 7.2+/-0.5 days (mean+/-S.E.M.), with a range of 4-11
      days. The follicular growth phase averaged 3.0+/-0.2 days, the static phase 1.4+/
      0.1, the regression phase 2.9+/-0.3 days, and the inter-wave interval was 4.2+/
      0.3 days. The mean growth rate during the growing phase was 1.8+/-0.1mm/day,
      while the duration of the interval from 6mm to maximum diameter was 1.4+/-0.1
      days. The mean maximum diameter of the dominant follicle was 8.4+/-0.3mm (range:
      6.2-11.2) and mean diameter of the largest subordinate follicle was 5.4+/-0.1mm.
      There was an inverse relationship between the size of the largest follicle and
      the total number of follicles (r=-0.21, P=0.002). Follicle activity alternated
      between ovaries in 77% of the waves, with 40% of dominant follicles present in
      the left ovary and 60% in the right ovary. Plasma estradiol-17beta concentrations
      also had a wave-like pattern, varying between 12.0 and 62.8 pmol/l. Plasma
      progesterone concentrations remained below 5.0 nmol/l and there was no
      ultrasonographic evidence of ovulation during the study.

PMID- 14698057
TI  - Regression analyses and motile sperm subpopulation structure study as improving
      tools in boar semen quality analysis.
AB  - A precise estimation of the fertilizing ability of a boar ejaculate would be very
      useful to improve pig assisted reproduction results. For this purpose, we tested
      the mathematical combination of several parameters of the boar semen quality
      analysis, including the computer-assisted semen motility analysis (CASA), as a
      predictive fertility tool. The utilized mathematical relations among parameters
      were logistic and linear regressions. Two mathematical models obtained by
      logistic regression involving Osmotic Resistance Test (ORT Test), Hyperosmotic
      Resistance Test (HRT Test) and viability of fresh samples, showed a significant
      (P<0.05) correlation between semen characteristics and conception rate. However,
      none of the obtained models produced a significant correlation model between
      semen characteristics and prolificacy. The CASA analyses show that three separate
      subpopulations of spermatozoa with different motility characteristics coexist in
      boar ejaculates. There were significant (P<0.001) differences in the distribution
      of these subpopulations among boars, but no clear relationship between motile
      subpopulation structure and fertility was obtained. Our results support the
      belief that the predictive use of the results obtained in a standard boar semen
      quality analysis can reasonably be achieved by applying logistic correlation
      analyses among several function parameters of boar semen quality analysis and in
      vivo conception rates obtained after artificial insemination (AI).

PMID- 14698058
TI  - Determining sample size for the morphological assessment of sperm.
AB  - Morphologic assessment of spermatozoa is an integral component in the analysis of
      semen. Whether a technician rapidly screening semen quality at a commercial stud,
      a veterinarian performing breeding soundness examinations, a clinician at a
      reference andrology laboratory providing auditing or diagnostic services, or a
      researcher evaluating morphology as a part of a fertility study, it is important
      to make an informed decision regarding the number of spermatozoa to include in
      the morphology assessment. Application of basic statistical principles such as
      the nature of proportions, level of confidence in an observed value, and the
      interaction of sample size with precision, can and should be used in the decision
      process. This paper outlines in detail the application of these statistical
      principles in relation to the morphologic assessment of spermatozoa. Guidelines
      on how these principles can be utilized in practical situations are discussed.
      Additionally, methodologies for comparison of results within and between
      laboratories (an area easily prone to misinterpretation) are reviewed. It is
      hoped that through the use of these fundamental statistical principles, this
      paper will bring clarity and delineation to the science of quantifying the
      morphology of spermatozoa.

PMID- 14698059
TI  - Oocyte transfer in mares with intrauterine or intraoviductal insemination using
      fresh, cooled, and frozen stallion semen.
AB  - The objectives were to compare embryo development rates after oocyte transfer
      with: (1) intrauterine or intraoviductal inseminations of fresh semen versus
      intraoviductal insemination of frozen semen; (2) intraoviductal versus
      intrauterine inseminations of cooled semen. In Experiment I, oocytes were
      transferred into the oviduct, and recipients were inseminated into the uterus
      with 1 x 10(9) fresh spermatozoa, or into the oviduct with 2 x 10(5) fresh or
      frozen-thawed spermatozoa. In Experiment II, semen was cooled to 5 degrees C
      before intrauterine insemination with 2 x 10(9) spermatozoa or intraoviductal
      inseminations of 2 x 10(5) spermatozoa (deposited with the oocytes). In
      Experiment I, embryo development rates were similar (P>0.05) for intrauterine
      versus intraoviductal inseminations when fresh semen was used (8/14, 57% and
      9/11, 82%, respectively). However, embryo development rates were lower (P<0.05)
      when frozen spermatozoa were placed within the oviduct (1/12, 8%). In Experiment
      II, embryo development rates were higher (P<0.05) when cooled semen was used for
      intrauterine (19/23, 83%) versus intraoviductal (4/16, 25%) inseminations. We
      concluded that intraoviductal insemination can be successfully performed using
      fresh spermatozoa. However, the use of cooled and frozen spermatozoa for
      intraoviductal inseminations was less successful, and needs further
      investigation.

PMID- 14698060
TI  - Epididymal sperm from the African buffalo (Syncerus caffer) can be frozen
      successfully with AndroMed and with Triladyl but the addition of bovine seminal
      plasma is detrimental.
AB  - Numerous diseases are carried and can be transmitted from the African buffalo
      (Syncerus caffer) to livestock. Buffaloes free of specific diseases (BFSD) are
      thus in demand amongst game farmers. Current BFSD derive from a small genetic
      pool and hence there is a special interest in bringing new genetic material into
      such herds. In this study epididymal sperm from 16 mature African buffalo bulls
      was frozen with Triladyl and AndroMed extender (Minitub, Tiefenbach, Germany)
      with and without addition of bovine seminal plasma. Post-thaw motility, longevity
      and acrosomal integrity were compared. In all but one animal, post-thaw motility
      was higher, although not always significant, if sperm was frozen with Triladyl
      than with AndroMed. Seminal plasma was detrimental to the post-thaw motility.
      Neither semen extender nor seminal plasma had an influence on post-thaw acrosomal
      integrity. It can be concluded that bovine seminal plasma at a concentration of
      10% is detrimental rather than beneficial for the post-thaw motility of African
      buffalo sperm. Even though being inferior AndroMed does, however, have the
      advantage that it is a defined semen extender and therefore clearly has a lower
      risk of contamination.

PMID- 14698061
TI  - The effect of eCG or estradiol at or after norgestomet removal on follicular
      dynamics, estrus and ovulation in early post-partum beef cows nursing calves.
AB  - In post-partum anestrous beef cows suckling calves, neither the choice of
      hormonal regime to ensure the presence of a healthy dominant follicle at the end
      of a progestagen treatment nor the optimum hormone to induce estrus and ovulation
      is clear. Twenty-eight beef cows, in good body condition, 25-30 days post-partum,
      were assigned to one of four treatments: (i) 3mg norgestomet (N) implant with 5mg
      estradiol valerate (EDV) and 3mg N injection at the time of insertion (Crestar)
      for 5 days followed by 600 IU eCG at the time of implant removal; (ii) Crestar
      for 5 days as in (i) followed by 0.75 mg estradiol benzoate (EDB) 24h later;
      (iii) Crestar for 9 days followed by 600 IU eCG at the time of implant removal;
      and (iv) Crestar for 9 days followed by 0.75 mg EDB 24h later. Ovarian scanning
      was preformed from 4 days before implant insertion until ovulation and 4 days
      postovulation to detect the CL. Daily blood samples were collected from day 20
      post-partum until second ovulation for FSH and E(2) assay. Data were analyzed
      using analysis of variance. There was no effect of the stage of follicle wave at
      the time of implant insertion on interval to new follicle wave emergence (range 1
      7 days; mean 4.7 days). FSH concentrations were decreased to 5.9+/-2.0 and 7.7+/
      1.1 ng/ml for pre- and post-selection cows 1 day after start of treatment;
      thereafter, they increased on Day 2 to 7.9+/-2.0 and 11.0+/-1.1 ng/ml and on Day
      3 to 10.3+/-2.7 and 11.4+/-1.7 ng/ml for pre- and post-selection cows,
      respectively, despite high-estradiol concentrations at that time. There was no
      effect of treatment on the interval from implant removal to ovulation (3.2-4.0
      days) or on the number of cows detected in estrus (26 of 27 cows). The size of
      the ovulatory follicle in cows given 0.75 mg EDB 24h post implant removal was
      decreased in animals at the pre-selection stage (12.2+/-0.1mm) of the follicle
      wave compared with those at the post-selection stage (15.3+/-0.9 mm) at implant
      removal. Cows given 600 IU eCG at the pre-selection phase of follicular growth
      had multiple ovulations (4.0+/-1.1). Cows given EDV at the start of a 5-day
      implant period had higher estradiol concentrations before and on the day of
      implant removal than those given EDV at the start of a 9-day implant period. The
      injection of 0.75 mg EDB 1 day after implant removal tended to increase
      concentrations of estradiol one day later. In conclusion, 5mg EDV and 3mg N at
      insertion of a 3mg N implant resulted in variable new follicle wave emergence 1-7
      days later in post-partum beef cows nursing calves (22 of 27); both eCG and EDB
      were equally effective at inducing estrus after implant removal in cows in good
      BCS, but eCG resulted in a significant increase in ovulation rate in cows treated
      before dominant follicle selection.

PMID- 14698062
TI  - Developmental competence of heifer oocytes selected using the brilliant cresyl
      blue (BCB) test.
AB  - The aim of this study was to evaluate the usefulness of the brilliant cresyl blue
      (BCB) test in the selection of more competent heifer oocytes for in vitro embryo
      production (IVEP). IVEP from selected BCB heifer oocytes was compared to IVEP
      from morphologically selected heifer (control group) and cow oocytes. BCB
      staining determines the activity of glucose-6-phosphate dehydrogenase (G6PD), an
      enzyme synthesized in growing oocytes but with less activity in grown oocytes.
      Six hundred and fifty seven heifer cumulus-oocyte complexes (COC) were classified
      morphologically as Grade 1-3 and exposed to 26 microM of BCB and classified as:
      blue (or grown) oocytes (BCB+) or unstained oocytes or growing oocytes (BCB-).
      Grade 1-3 heifer oocytes showed significantly different percentages of BCB+
      oocytes (78.6, 66.2, and 51.1%, respectively; P<0.05). The diameter of BCB+
      oocytes was significantly higher than BCB- oocytes (152.6+/-5.8 microm and 147+/
      5.9 microm, respectively; P<0.001). The percentage of BCB+ oocytes reaching the
      blastocyst stage was significantly higher than those of BCB- and control heifer
      oocytes (12.3, 1.6, and 5.2%, respectively; P<0.05), but lower than those of cow
      oocytes (30.0%; P<0.05). In conclusion, heifer oocytes selected by the BCB test
      (BCB+) are larger and more competent for IVEP than control heifer oocytes.
      However, fewer heifer oocytes selected using the BCB test develop to blastocyst
      stage compared to cow oocytes.

PMID- 14698063
TI  - Inhibitory effect of IGF-I on induced apoptosis in mouse preimplantation embryos
      cultured in vitro.
AB  - Insulin-like growth factor I (IGF-I) has been shown to promote mammalian early
      embryo development. Increased cell division or decreased cell death have been
      proposed as two main possible mechanisms in its effect. Here we examine the
      nature of this promoting effect in a model situation. Camptothecin (0.01
      microg/ml) and actimomycin D (0.005 microg/ml) were used to induce apoptosis.
      Four-cell mouse embryos were cultured in vitro to blastocyst stage in the
      temporary (15 h) presence or absence of apoptotic inductors and in the permanent
      presence or absence of IGF-I (100 ng/ml). Embryos were assessed by morphological
      triple staining (Hoechst 33342, propidium iodide, Calcein AM) and comet assay on
      Day 5, 120 h after administration of hCG. The number of nuclei, the blastocyst
      formation, the proportion of embryos containing fragmented DNA and the percentage
      of apoptotic and secondary necrotic nuclei were assessed. Both inductors of
      apoptosis significantly increased the percentage of apoptotic and secondary
      necrotic cells and reduced total cell counts (camptothecin, P>0.001; actinomycin
      D, P>0.001). When IGF-I was added to the culture medium in the presence of an
      apoptosis inductor, apoptosis incidence was significantly decreased (P<0.001).
      The addition of IGF-I into control samples also decreased the percentage of
      apoptotic and secondary necrotic cells. In contrast, IGF-I addition had no
      significant influence on embryo development (P>0.05). Our data suggest a primary
      role for IGF-I as an apoptotic survival factor in mouse preimplantation embryos
      in specific conditions.

PMID- 14698065
TI  - Effect of semen collection practices on sperm characteristics before and after
      storage and on fertility of stallions.
AB  - This study analyzed effects of different methods and intervals of semen
      collection on the quantity and quality of fresh, cool-stored, and frozen-thawed
      sperm and fertility of AI stallions. In Experiment 1, ejaculates were obtained
      from six stallions (72 ejaculates per stallion) using fractionated versus non
      fractionated semen collection techniques. Initial sperm quality of the first
      three jets of the ejaculate was not different from that of total ejaculates.
      Centrifugation of sperm-rich fractions before freezing improved post-thaw
      motility and sperm membrane integrity when compared to non-centrifuged sperm-rich
      fractions or non-fractionated centrifuged ejaculates (P<0.05). In Experiment 2,
      semen from four stallions (60-70 ejaculates per stallion) was collected either
      once daily or two times 1h apart every 48 h. The first ejaculates of double
      collections had significantly higher sperm concentrations, percentages of
      progressively motile sperm (PMS) after storage for 24h at 5 degrees C and lower
      percentages of midpiece alterations than single daily ejaculates. Semen collected
      once daily showed significantly lower values of live sperm after freezing and
      thawing than the first ejaculate of two ejaculates collected 1h apart every 48 h.
      In Experiment 3, semen was collected from 36 stallions (> or =12 ejaculates per
      stallion) during the non-breeding season and the time to ejaculation and the
      number of mounts was recorded. When time to ejaculation and the number of mounts
      increased, volume and total sperm count (TSC) also increased (P<0.05), whereas a
      decrease was observed in sperm concentration, percentage of PMS after storage for
      24 h at 5 degrees C, percentage of membrane-intact sperm in fresh semen (P<0.05)
      as well as motility and percentage of membrane-intact sperm of frozen-thawed
      sperm (P<0.05). In Experiment 4, AI data of 71 stallions were retrospectively
      analyzed for the effect of number of mounts per ejaculation and frequency, time
      interval of semen collections on pregnancy, and foaling rates (FRs) of mares.
      Semen volume increased, but sperm concentration and percentage of PMS after 24-h
      cool-storage decreased with increasing number of mounts on the phantom (P<0.05).
      A statistically significant inter-relationship was demonstrated between frequency
      and interval of semen collection and FR. Mares inseminated with stallions from
      which semen was collected frequently (> or =1 on an average per day) showed
      significantly higher FRs than mares inseminated with semen from stallions with a
      daily collection frequency of 0.5-1 or <0.5. FR of mares inseminated with
      stallions having 0.5-1 days between semen collections was significantly better
      than FR of mares that were inseminated with stallions having semen collection
      intervals of 1-1.5 days or >2.5 days.

PMID- 14698064
TI  - The impact of induced stress during days 13 and 14 of pregnancy on the
      composition of allantoic fluid and conceptus development in sows.
AB  - Stress due to regrouping of breeding females is difficult to avoid completely in
      loose-housing systems. The effects of stress during the maternal recognition of
      pregnancy on fetal development and survival at Day 30 of pregnancy was,
      therefore, studied in 17 sows allocated into one control (C-) group, one group
      deprived of food during Days 13 and 14 (FD-), and one group (A-), which was
      treated with ACTH (0.01 mg/kg body weight of Synacthen Depot) every sixth hour
      during the same period. Total number of fetuses, fetal survival rate, volume of
      allantoic fluid, and the weight and length of total fetal unit, placentas,
      allantochorion and fetuses were determined. The concentrations of progesterone
      (P4), PGFM, PGF2, PGE, estrone-sulfate, and estradiol-17beta in the allantoic
      fluid were analyzed. No significant differences between groups were found for any
      parameter measured except for P4. Food deprivation increased P4 concentration in
      the allantoic fluid, and there was a positive correlation between the P4
      concentration and the weight of the placenta. It is, therefore, suggested that P4
      influences the placenta size among food-deprived sows.

PMID- 14698066
TI  - Ultrasonography in early pregnancy diagnosis and measurements of fetal size in
      reindeer (Rangifer tarandus tarandus).
AB  - Transrectal or transabdominal examinations of 13 pluriparous reindeer (Rangifer
      tarandus tarandus) by ultrasonography from the start of mating until week 20 of
      gestation were conducted to find out when pregnancy could first be detected and
      to describe fetal development in early pregnancy. The examinations (n=35 per
      animal) were performed with a 5 MHz linear transducer from 7th October until 1st
      January and with a 3 MHz sector transducer from that time until 24th February.
      Time of pregnancy diagnosis by ultrasonography, the first fetal heartbeat and
      measurements of crown-rump length, chest width and chest depth were recorded
      during the examinations. Pregnancy was diagnosed by transrectal ultrasonography
      between the weeks 3 and 7 of gestation. The accuracy of the pregnancy diagnosis,
      defined as the proportion of females correctly detected to be pregnant, was 15%
      at week 3, 46% at week 4, 77% at week 5, and 92% at week 6 of gestation. Fetal
      heartbeat was first detected between the weeks 5 and 8 of gestation. The first
      measurements of crown-rump length were made on week 3 of gestation, of chest
      width on week 4 and of chest depth on week 5 of gestation. Chest width and depth
      were detectable until the end of the study at week 20 of gestation. Transrectal
      ultrasonography is an efficient tool in early pregnancy diagnosis of reindeer.
      The fetal growth curves obtained by ultrasonography resembled those obtained in
      previous morphological studies.

PMID- 14698067
TI  - The use of mifepristone to reduce unwanted pregnancy and associated health and
      social risks.

PMID- 14698068
TI  - Reducing the need for abortion.

PMID- 14698069
TI  - Summary of evidence and research needs on the use of mifepristone in fertility
      regulation: consensus from the conference.
AB  - The conference on the use of mifepristone to reduce unwanted pregnancy, sponsored
      by the World Health Organization, Concept Foundation and the Rockefeller
      Foundation, took place in Bellagio, Italy, between 24 and 28 September 2001. The
      objective of the conference was to review the scientific information and to
      evaluate the use of mifepristone for emergency contraception, luteal
      contraception and menstrual induction. Mifepristone is highly effective for
      emergency contraception but its advantages and disadvantages in comparison with
      levonorgestrel need to be further studied. Data indicate that mifepristone alone
      or in combination with misoprostol has potential for occasional use for women
      seeking help following repeated unprotected intercourse and/or when the interval
      between intercourse and treatment is more then 120 h. Administration of
      mifepristone immediately after ovulation seems to be an effective contraceptive
      method. However, before it can be used commonly, there is a need for a simple and
      inexpensive method to identify the right time in the cycle. Once-a-month
      treatment with mifepristone and misoprostol at the expected time of menstruation
      is not a practical method due to bleeding irregularities and timing of treatment.
      Menstrual induction with mifepristone and a suitable prostaglandin analogue is
      highly effective. A randomized comparison with manual vacuum aspiration is,
      however, needed before it can be recommended for routine use.

PMID- 14698070
TI  - Pharmacological properties of mifepristone: toxicology and safety in animal and
      human studies.
AB  - Roussel Uclaf in partnership with the INSERM unit of Prof. E.E. Baulieu first
      discovered mifepristone (RU486) as part of a large research program on steroidal
      compounds with antihormone properties. Exhibiting a strong affinity to the
      progesterone and the glucocorticoid receptors, mifepristone exerted competitive
      antagonism to these hormones both in in vitro and in animal experiments. Due to
      its antiprogesterone activity, it was proposed that mifepristone be used for the
      termination of early human pregnancy. Mifepristone, at a dose of 600 mg initially
      used alone, was then used with a subsequent low dose of prostaglandin that led to
      a success rate of 95% as a medical method for early termination of pregnancy
      (TOP). Its use was extended to other indications, such as cervical dilatation
      prior to surgical TOP in the first trimester, therapeutic TOP for medical reasons
      beyond the first trimester, and for labor induction in case of fetal death in
      utero. The efficacy and safety of this treatment has been confirmed based on its
      use for over a decade, with close adherence to the approved recommendations. This
      paper describes the safety studies conducted in animals as well as the safety
      follow-up and side effects reported with use of the compound in various
      indications either approved or unapproved. The rationale for warnings and
      contraindications for use of the product are also explained. At lower doses, the
      molecule has proven promising for contraceptive purposes with few reported side
      effects. However, development of the product for this indication would require
      long-term studies. Although political and philosophical obstacles have delayed
      research, the use of mifepristone for other potential indications in gynecology
      or oncology should be investigated.

PMID- 14698071
TI  - The pharmacokinetics of mifepristone in humans reveal insights into differential
      mechanisms of antiprogestin action.
AB  - The pharmacokinetics of mifepristone is characterized by rapid absorption, a long
      half-life of 25-30 h, and high micromolar serum concentrations following
      ingestion of doses of >/=100 mg of the drug. The serum transport protein-alpha 1
      acid glycoprotein (AAG)-regulates the serum kinetics of mifepristone in man.
      Binding to AAG limits the tissue availability of mifepristone, explaining its low
      volume of distribution and low metabolic clearance rate of 0.55 L/kg per day. In
      addition, the similar serum levels of mifepristone following ingestion of single
      doses exceeding 100 mg can be explained by saturation of the binding capacity of
      serum AAG. Mifepristone is extensively metabolized by demethylation and
      hydroxylation, the initial metabolic steps being catalyzed by the cytochrome P
      450 enzyme CYP3A4. The three most proximal metabolites, namely, monodemethylated,
      didemethylated and hydroxylated metabolites of mifepristone, all retain
      considerable affinity toward human progesterone and glucocorticoid receptors.
      Also, the serum levels of these three metabolites are in ranges similar to those
      of the parent mifepristone. Thus, the combined pool of mifepristone-plus its
      metabolites-seems to be responsible for the biological actions of mifepristone.
      Recent clinical studies on pregnancy termination and emergency contraception have
      focused on optimization of the dose of mifepristone. In these studies it has
      become apparent that the doses efficient for pregnancy termination differ from
      those needed in emergency contraception-mifepristone is effective in emergency
      contraception at a dose of 10 mg, which results in linear pharmacokinetics.
      However, the >/=200 mg doses of mifepristone needed for optimal abortifacient
      effects of mifepristone result in saturation of serum AAG and thus nonlinear
      pharmacokinetics. In view of the pharmacokinetic data, it may be speculated that
      dosing of mifepristone for pregnancy termination and for emergency contraception
      could be reduced to approximately 100 mg and 2-5 mg, respectively. It remains to
      be seen whether the newly synthesized, more selective antiprogestins will prove
      more efficacious in the clinical arena.

PMID- 14698072
TI  - Pharmacokinetics of 10 mg of mifepristone.
AB  - The results of several randomized studies have verified the efficacy of 10 mg
      mifepristone in emergency contraception. In the present study we characterized
      the pharmacokinetics of 10 mg mifepristone. Eight healthy female volunteers
      received a single oral dose of mifepristone on the day 10 or 11 of their
      menstrual cycle. Blood samples were collected at 0, 1, 2, 4 and 8 h, daily for
      the next 6 days and on day 10 after mifepristone. Mifepristone concentrations
      were determined by radioimmunoassay preceded by column chromatography. A peak
      level of 1.41 +/- 0.31 micromol/L (mean +/- SD) was measured at 1 h. Individual
      elimination phase half-lives varied from 15.3 to 26.8 h, the mean (+/- SD) value
      being 19.6 +/- 4.50 h. Serum mifepristone concentrations exceeded 10 nmol/L in
      all volunteers for an average of 4.9 days. The pharmacokinetic data on 10 mg
      mifepristone are in line with previous pharmacokinetic and clinical data, and
      encourage further development of the 10-mg dose in emergency contraception.

PMID- 14698073
TI  - Expanded clinical trial of emergency contraception with 10 mg mifepristone.
AB  - We conducted a clinical single-arm trial to evaluate the effectiveness of 10 mg
      mifepristone for emergency contraception (EC) in a large population in China. The
      participating centers were 31 family-planning clinics and hospitals in the
      following 19 provinces or municipalities in China: Beijing, Shanghai, Tianjin,
      Harbin, Changchun, Shengyang, Shijiazhuang, Zhengzhou, Taiyuan, Nanjing, Jinan,
      Hangzhou, Guangzhou, Wuhan, Changsha, Chongqing, Guiyang, Chengdu, Kunming. A
      total of 4945 women requesting EC within 120 h after a single act of unprotected
      intercourse were recruited and treated with 10 mg mifepristone. A total of 28
      women were lost to follow-up, and 4917 women were included in the analysis, of
      whom, 69 became pregnant. The combined pregnancy rate was 1.4 [95% confidence
      interval (CI): 1.0-1.9] and the percentage of pregnancies prevented was 82.2%
      (95% CI: 77.5-86.2%). There was a significant inverse trend in pregnancy rate
      with body mass index that disappeared when adjusted for other variables. The
      pregnancy risk was double among nulliparous women compared to parous women (2.3%
      compared to 1.0%), and it increased by a factor of 1.5 when the treatment was
      administered at 25-48 h and at 49-72 h compared to administration within 24 h,
      although this association was not significant. The risk of pregnancy was higher
      if intercourse took place during the follicular or preovulatory phase of the
      cycle. Women having repeated intercourse after treatment without any
      contraceptive methods had a dramatic increase in the risk of pregnancy, while
      those who used contraceptives had similar risk to those without acts. Side
      effects were mild and present in only small proportions of women: nausea and
      vomiting in 9% and other side effects in 2-3%. Delay of menstruation of 7 days or
      more occurred in 6.5% of women. The expanded study confirmed the high efficacy
      and safety of 10 mg mifepristone for EC.

PMID- 14698075
TI  - Meta-analyses of randomized trials comparing different doses of mifepristone in
      emergency contraception.
AB  - There is some evidence from randomized trials that different doses of
      mifepristone for emergency contraception do not differ in efficacy in the range
      from 10 mg to 600 mg. Lower doses have a better side effect profile and are
      cheaper and therefore they would be preferable in the absence of a dose effect.
      However, the lack of significance is not evidence of absence of an effect. More
      evidence can be obtained by combining results of trials. We present meta-analyses
      of randomized trials comparing doses of mifepristone for emergency contraception
      from 5 mg to 600 mg, with regard to the efficacy to prevent unwanted pregnancies.
      We use two approaches for analysis, one using only within-trial information and
      another one combining within-trial with between-trial information. We discuss the
      results in terms of equivalence. There is some evidence of a small dose effect on
      efficacy in the lower range of doses (<50 mg). The pregnancy rate increases by a
      factor of 1.6 when the dose of 10 mg is used instead of 25 mg (95% confidence
      interval: 1.1-2.4). In terms of the number of women needed to treat, however,
      using 10 mg in the place of 25 mg implies having one extra pregnancy every 146
      women requesting emergency contraception, which might be a low cost compared to
      the benefit of more women having access to treatment.

PMID- 14698074
TI  - Combined estimates of effectiveness of mifepristone 10 mg in emergency
      contraception.
AB  - The present paper combines the estimates of efficacy and side effects of 10 mg
      mifepristone for emergency contraception obtained from randomized trials. A total
      of 6083 women participating in 12 randomized trials and receiving 10 mg
      mifepristone for emergency contraception up to 120 h after intercourse, were
      analyzed for efficacy. Between 4188 and 5833 women were analyzed for side effects
      and 3601 for delay of menses of more than 7 days. Prevented fractions, the effect
      of delay and of further acts of intercourse after treatment administration were
      analyzed in 3440 women, using individual data. The combined pregnancy rate from
      all the 12 trials was 1.7% [101/6083, 95% confidence interval (CI): 1.3-2.2].
      From the three trials providing individual data, the combined pregnancy rate was
      1.3% (45/3440, 95% CI: 0.9-1.7) and the estimate of pregnancies prevented was
      83.4% (95% CI: 77.4-87.8). There was a sharp decline in efficacy when treatment
      was administered during the 5th day after intercourse compared to administration
      during the 1st day, the odds of pregnancy increasing by a factor of 5.3 (95% CI:
      1.9-14.9). The relative risk of pregnancy was about 28 times higher among women
      with unprotected acts of coitus between treatment administration and the onset of
      next menses, compared with women reporting none [odds ratio (OR) = 27.6, 95% CI:
      12.7-60.2]. The increase in risk for women reporting protected acts of
      intercourse during this interval was not statistically significant (OR = 1.8, 95%
      CI: 0.9-3.8). There was a large heterogeneity among trials in all side effects
      and delay of menses of more than 7 days (all had p < 0.0001 for the test of
      homogeneity). The percentage of women with nausea ranged from 0.0-19.4% (highest
      upper 95% confidence limit: 23.0%), that of vomiting from 0.0-4.3% (highest upper
      95% confidence limit: 6.1%), that of lower abdominal pain from 4.3-19.1% (highest
      upper 95% confidence limit: 22.7%). The percentage of women with delay of menses
      of more than 7 days ranged from 4.3-25.8% (highest upper 95% confidence limit:
      34.1%). We conclude that 10 mg mifepristone is an effective emergency
      contraception regimen, with an acceptable side-effects profile. Postponing
      treatment until the 5th day seriously decreases efficacy. The risk of pregnancy
      is dramatically increased among women having unprotected acts of intercourse
      between treatment administration and the onset of next menses. This risk may be
      enhanced for women whose ovulation is postponed by treatment.

PMID- 14698076
TI  - A multiparametric study of the action of mifepristone used in emergency
      contraception using the Rhesus monkey as a primate model.
AB  - Mifepristone is a potent agent used in emergency contraception (EC). In the
      present study, we examined the contraceptive efficacy of mifepristone used in EC
      and then, using the model of mifepristone-based EC, we investigated its mechanism
      of action in the rhesus monkey. Sexually mature females were allowed to
      cohabitate with male animals from 1600 to 900 h of any one day of days 8-17 of
      cycle without (Group I; n = 6) and with a single dose of mifepristone (Group II,
      n = 31, 25 mg per animal, subcutaneous) 72 h postcoitus. Blood samples from all
      animals of Groups I and II were used to determine the concentrations of estradiol
      (E), progesterone (P) and chorionic gonadotrophin in peripheral circulation for
      retrospective analysis of the days of ovulation and blastocyst implantation. Four
      out of six animals (66.6%) in Group I became pregnant, while all 31 monkeys in
      Group II failed to establish pregnancy along with marginal changes in serum
      concentrations of E and P. In the second part of the study, animals were
      subjected to the same experimental protocol followed by collection of endometrial
      tissue samples on cycle day 22 from animals of both Group I (n = 6) and Group II
      (n = 24). Endometrial samples were subjected to morphological analysis including
      mitotic index, immunohistochemistry for vascular endothelial growth factor
      (VEGF), leukemia inhibitory factor (LIF), transforming growth factor beta1,
      estradiol receptor (ER), progesterone receptor (PR), proliferating cell nuclear
      antigen, placental protein 14 (PP 14) and detection of apoptosis by terminal nick
      end labeling method followed by histometric analysis. The results were
      retrospectively analyzed between the two groups on the basis of the day of
      treatment after ovulation: early luteal phase (days 0-3 postovulation) and mid
      luteal phase (days 4-7 after ovulation). Mifepristone used in EC in the present
      study resulted in general loss of functional integrity of epithelial compartment
      characterized by loss of secretory maturation, increased apoptosis and higher
      degree of degeneration along with decreased expression of VEGF, LIF, PP14 and ER,
      while PR level increased as compared to control samples. The vascular compartment
      appeared to be compromised along with affected morphological features and
      decreased expression of VEGF, LIF, ER and PR following the administration of
      mifepristone. It appears that mifepristone used in EC alters the physiological
      homeostasis in epithelial and vascular compartments of implantation stage
      endometrium rendering it hostile to blastocyst implantation. Furthermore, the
      degree to which the endometrial function is affected largely depends on the day
      of mifepristone treatment in a parameter-specific manner resulting in a higher
      degree of degenerative changes in samples obtained from animals who received
      mifepristone during mid-luteal phase of cycles.

PMID- 14698077
TI  - Mechanisms of action of mifepristone when used for emergency contraception.
AB  - An emergency contraceptive method is used after coitus but before pregnancy
      occurs. The use of emergency contraception is largely underutilized worldwide.
      Recently, treatment with 10 mg mifepristone as a single dose has emerged as one
      of the most effective hormonal methods for emergency contraception, with very low
      side effects. However, the mechanism of action of mifepristone in humans when
      used for contraceptive purposes and especially for emergency contraception
      remains largely unknown. The objective of this review is to summarize available
      data on the effect of mifepristone on female reproductive functions relevant to
      emergency use of the compound. Taken together, available data from studies in
      humans indicate that the contraceptive effect of mifepristone used as a single
      low dose for emergency contraception is mainly due to impairment of ovarian
      function, either by blocking or postponing the luteinizing hormone surge, rather
      than to inhibiting of implantation.

PMID- 14698078
TI  - Luteal phase treatment with mifepristone and misoprostol for fertility
      regulation.
AB  - Emergency contraception (EC) with 10 mg mifepristone can prevent pregnancy up to
      5 days after a single act of unprotected intercourse. No methods have been shown
      to be effective when treatment is administered more than 5 days after a single
      unprotected act or after several unprotected acts. Therefore, we tested, among
      699 Chinese women requesting EC and exposed to the risk of pregnancy described,
      the potential of 100 mg mifepristone followed 2 days later by 0.4 mg misoprostol
      orally, when administered in the luteal phase of the cycle. At the time of
      treatment urinary pregnancy test had to be negative. Despite treatment, 25 women
      (2.7%) became pregnant. Among women with treatment delayed more than 5 days, the
      pregnancy rate was related to the number of acts of intercourse before treatment,
      being 1.4% with one episode and increasing to 6.5% when the number of episodes
      was two or more (relative risk = 4.62, 95% CI: 1.06-20.18). Side effects within a
      week after treatment were mild, and most women (57.2%) had menstruation within 3
      days as expected. An occasional treatment with mifepristone in combination with
      misoprostol could provide an option for preventing unwanted pregnancies in women
      who are late for EC.

PMID- 14698079
TI  - Mifepristone for luteal phase contraception.
AB  - The concept of luteal phase contraception and the use of mifepristone in clinical
      trials, which allows for testing of its validity, as well as clinical
      pharmacological research designed to understand its mode of action, are reviewed.
      Early luteal phase administration has a variety of morphological, physiological
      and biochemical effects on the endometrium that are likely to interfere with
      embryonic-endometrial interactions. In fact, specifically designed pilot clinical
      trials as well as data derived from emergency contraception studies indicate that
      early luteal phase administration of mifepristone is highly effective in
      preventing pregnancy, with minimal disturbance of hormonal parameters or
      menstrual cyclicity. Mid and late luteal phase administration of mifepristone at
      doses above 25 mg are highly effective in inducing endometrial bleeding in
      nonconceptional cycles. However, administration of mifepristone within the period
      between implantation and expected menses fails to induce bleeding in a
      significant proportion of cases, and furthermore the bleeding induced does not
      insure the termination of pregnancy. While the data suggest there is potential
      for a once-a-month contraceptive pill, it is likely that no molecule endowed with
      partial agonistic properties, like mifepristone, will completely and reliably
      suppress the essential functions of progesterone in order to achieve
      contraceptive efficacy comparable to that of modern contraceptive methods.

PMID- 14698080
TI  - Menstrual induction with mifepristone and misoprostol.
AB  - Menstrual induction refers to early uterine evacuation without laboratory
      confirmation of pregnancy in women with delayed menses. Mechanical aspiration is
      the method used in many countries but, as suggested by a pilot study,
      mifepristone followed by a prostaglandin analogue could also be effective. We
      launched the present study to evaluate the efficacy and side effects of 150 mg of
      mifepristone, followed 2 days later by 0.4 mg misoprostol vaginally, for
      menstrual induction among women with a menstrual delay of up to 7 days. The
      outcome of treatment was uterine evacuation, which could mean menstruation or
      termination of early pregnancy. A total of 720 women were recruited. The mean
      delay of menstruation at recruitment was 4.9 (SD = 1.7) days. Retrospective
      analysis of human chorionic gonadotropin from serum samples taken at admission
      showed that 492 (68.3%) women were pregnant at admission, and 228 (31.7%) women
      had delayed menstruation without pregnancy. One nonpregnant woman was lost to
      follow-up. Bleeding was induced in 479 (97.4%) pregnant women and in 222 (97.8%)
      nonpregnant women. Among the pregnant women, 455 (92.5%) had complete abortion,
      12 (2.4%) had incomplete abortion and pregnancy continued in 25 (5.1%) women,
      including one ectopic pregnancy. Side effects were mild and uncommon. We conclude
      that 95.8% of the women treated had the expected outcome. Further research is
      needed to compare the efficacy, safety and acceptability of the medical regimen
      to vacuum aspiration. A rather high continuing pregnancy rate in this study is a
      concern.

PMID- 14698081
TI  - The possibility of using mifepristone for menstrual induction.
AB  - Menstrual induction is a variant of suction aspiration that was originally
      defined to be performed in women with a menstrual delay of up to 2-3 weeks
      without knowing if the women is pregnant or not. Prerequisites for a
      pharmacological method for menstrual induction are a high efficacy to induce a
      bleeding in nonpregnant women and an expulsion of the pregnancy in pregnant
      women. Treatment with prostaglandins, specifically intramuscular sulprostone, can
      be as effective as suction aspiration for menstrual induction. However, the
      administration of prostaglandin in therapeutically effective doses was associated
      with a high frequency of gastrointestinal side effects and, to a lesser extent,
      of strong abdominal pain, which limited their routine use. More recent studies
      indicate that mifepristone in combination with either misoprostol or gemeprost is
      a more promising alternative. Further studies to identify the best treatment
      schedule are, however, needed, as is a randomized comparison with suction
      aspiration before a pharmaceutical method can be recommended.

PMID- 14698082
TI  - Expression of Trk A receptors in the mammalian inner ear.
AB  - Tyrosine kinase receptors, including Trk A, Trk B and Trk C, participate in many
      different biological processes that are regulated by neurotrophic factors. Nerve
      growth factor (NGF)-triggered Trk A signaling is involved in growth, survival and
      differentiation of neurons in the central nervous system and in neural crest
      derived cells. Trk A, Trk B and Trk C expression has been reported in the rat
      ventral cochlear nucleus. In the present study, we explored the
      immunocytochemical distribution of Trk A in the rodent inner ear. Rat and mouse
      cochleae were immunolabeled with a rabbit anti-Trk A polyclonal antibody
      (Chemicon) that has no reported cross-reactivity with Trk B and Trk C. In
      embryonic day 16 mice, no Trk A immunolabeling could be detected in the
      developing neuroepithelium. At postnatal day 6, weak Trk A labeling could be
      observed in both inner and outer hair cells. At postnatal day 12, enhanced
      punctate Trk A immunoexpression was present in hair cells. In adult mice and
      rats, intense Trk A labeling was observed in outer and inner hair cell bodies, in
      supporting cell bodies throughout the cochlea, and in spiral ganglion neurons.
      Trk A was not observed in stria vascularis, hair cell stereocilia, nor in the Trk
      B- and Trk C-rich cerebellum. This distribution pattern of Trk A suggests that
      its ligand, NGF, exerts significant trophic effects in the rodent inner ear.

PMID- 14698084
TI  - Expression patterns of claudins, tight junction adhesion molecules, in the inner
      ear.
AB  - Tight junctions (TJs) are indispensable for the establishment of compositionally
      distinct fluid compartments in the inner ear, but our knowledge of the claudins,
      TJ adhesion molecules, in the inner ear is still fragmentary. We examined the
      expression and distribution of claudin-1 to claudin-18 (except for claudin-7, -13
      and -17) in the inner ear by immunofluorescence microscopy. In the cochlea, the
      organ of Corti expressed claudin-1, -2, -3, -9, -10, -12, -14 and -18. In the
      stria vascularis, claudin-1, -2, -3, -8, -9, -10, -12, -14 and -18 were expressed
      in the marginal cells, whereas the basal cells were positive only for claudin-11.
      In Reissner's membrane and the spiral limbus, the expression of claudin-1, -2, 
      3, -8, -9, -10, -12, -14 and -18 was detected. Furthermore, in the vestibule,
      claudin-1, -3, -9, -12, -14 and -18 were expressed in the sensory epithelia,
      whereas in the dark cell area claudin-1, -3, -8, -9, -12, -14 and -18 were
      detectable. These findings, i.e., very complex expression patterns of claudin
      species in the inner ear, would reflect the importance and the complexity of the
      barrier function of TJs in the inner ear.

PMID- 14698083
TI  - The use of distortion product otoacoustic emissions in the estimation of hearing
      and sensory cell loss in noise-damaged cochleas.
AB  - Distortion product otoacoustic emissions (DPOAE), permanent threshold shifts
      (PTS) and outer hair cell (OHC) losses were analyzed in a population of 187 noise
      exposed chinchillas to determine the predictive accuracy (sensitivity and
      specificity) of the DPOAE for PTS and OHC loss. Auditory evoked potentials (AEP)
      recorded from the inferior colliculus of the brainstem were used to estimate
      hearing thresholds and surface preparation histology was used to determine
      sensory cell loss. The overlapping cumulative distributions and high variability
      in emission responses for both PTS and OHC loss made it difficult to predict AEP
      threshold and OHC loss from DPOAE level measurements alone. Using a strict
      criterion (i.e. emissions better than the 5th percentile of the preexposure DPOAE
      level, and PTS< or = 5 dB or OHC loss< or = 5%), it was found that the
      postexposure DPOAE level could be used with reasonable confidence to determine if
      the status of peripheral auditory system was either normal (i.e. PTS< or = 5 dB)
      or abnormal (PTS>30 dB or OHC loss>40%). However, the high variability of
      individual DPOAE responses resulted in a broad region of 'uncertainty' (i.e.
      5<PTS< or = 30 dB and 5%<OHC loss< or = 40%) making it difficult in the
      chinchilla model to use the postexposure DPOAE level with confidence to predict
      in individual subjects the amount of PTS or OHC loss. Our results also indicate
      that significant reductions in the amplitude of the DPOAE are related primarily
      to a systematic loss of OHCs, and that a postexposure DPOAE level< or = 10 dB
      SPL, obtained with a low frequency primary level of 65 dB SPL, represents a
      criterion value which can serve as an indication of significant OHC loss (> or =
      50%) or PTS (> or = 35 dB) in noise-exposed chinchillas. Based on an exponential
      regression analysis of individual subjects, correlations were higher for
      PTS/DPOAE than for OHC loss/DPOAE.

PMID- 14698085
TI  - BK channels mediate the voltage-dependent outward current in type I spiral
      ligament fibrocytes.
AB  - Recent experimental and clinical studies have provided considerable evidence to
      support the phenomenon of K(+) recycling in the mammalian cochlea. However, the
      precise cellular and molecular mechanisms underlying and regulating this process
      remain only partially understood. Here, we report that cultured type I spiral
      ligament fibrocytes (SLFs), a major component of the K(+) recycling pathway, have
      a dominant K(+) membrane conductance that is mediated by BK channels. The
      averaged half-maximal voltage-dependent membrane potential for the whole-cell
      currents was 70+/-1.2 mV at 1 nM intracellular free Ca(2+) and shifted to 38+/
      0.2 mV at 20 microM intracellular free Ca(2+) (n=4-6). The reversal potential of
      whole-cell tail currents against different bath K(+) concentrations was 52 mV per
      decade (n=3-6). The sequence of relative ion permeability of the whole-cell
      conductance was K(+)>Rb(+)z.Gt;Cs(+)>Na(+) (n=5-17). The whole-cell currents were
      inhibited by extracellular tetraethylammonium and iberiotoxin (IbTx) with IC(50)
      values of 0.07 mM and 0.013 microM, respectively (n=3-7). The membrane potentials
      of type I SLFs measured with conventional zero-current whole-cell configuration
      were highly K(+)-selective and sensitive to IbTx (n=4-9). In addition, the BK
      channels in these cells exhibited voltage-dependent and incomplete inactivation
      properties and the recovery time was estimated to be approximately 6 s with
      repetitive voltage pulses from -70 to 80 mV (n=3). These data suggest that BK
      channels in type I SLFs play a major role in regulating the intracellular
      electrochemical gradient in the lateral wall syncytium responsible for
      facilitating the K(+) movement from perilymph to the stria vascularis.

PMID- 14698086
TI  - Round window pH manipulation alters the ototoxicity of systemic cisplatin.
AB  - The effect of manipulation of pH on the ototoxicity of systemic cisplatin was
      studied in Wistar rats. After control auditory brainstem responses (ABR) were
      performed, the auditory bullae were opened and acidic (pH 6.0), neutral (pH 7.4)
      or basic (pH 9.0) phosphate-buffered saline (PBS) was applied to fill the round
      window niche (RWN). After 30 min, 13 mg/kg cisplatin solution or saline was
      administered intraperitoneally. After 3 days, follow-up ABRs were performed and
      cochleae were processed for morphological analysis. Animals that received basic
      PBS on the RWN and cisplatin intraperitoneally had significantly smaller ABR
      threshold shifts compared to rats pretreated with neutral pH buffer (P<0.05).
      Animals that received acidic PBS on the RWN and systemic cisplatin showed
      significantly greater ABR threshold shifts compared to those pretreated with
      neutral pH buffer (P<0.05). No significant threshold changes were observed in
      animals that received buffer of any pH on the RWN, followed by saline
      intraperitoneally. Semiquantitative analysis of hair cell survival confirmed a
      protective effect by basic PBS against cisplatin and a synergistic effect by
      acidic PBS on cisplatin ototoxicity (P<0.05). It appears that changes in cochlear
      pH can modulate the ototoxic effects of systemically applied cisplatin.

PMID- 14698087
TI  - Imaging of the cortical cytoskeleton of guinea pig outer hair cells using atomic
      force microscopy.
AB  - Mammalian outer hair cells (OHCs) are known to respond to acoustical stimulation
      with elongation and contraction of the cells' cylindrical soma in vivo, and this
      motility is related to both the protein motors distributed along the OHC plasma
      membrane and the cytoskeleton beneath it. Therefore, the cytoskeleton seems to
      play an important role in the motility of the OHC. Recently, an atomic force
      microscope (AFM) was used to investigate the OHC cytoskeleton under physiological
      conditions. However, details were not made clear in that study. In this study,
      the ultrastructure of the cytoskeleton of fixed OHCs of guinea pigs, which were
      extracted with Triton X-100, was investigated using the AFM. As a result, the
      cortical cytoskeleton, which is formed by discrete oriented domains, was imaged,
      and circumferential filaments and cross-links were observed within the domain.
      Morphological change of the cytoskeleton of the OHC induced by diamide treatment
      was then examined using the AFM, and reduction of cross-links was observed. The
      examination indicates that the cortical cytoskeleton comprises circumferential
      actin filaments and spectrin cross-links.

PMID- 14698088
TI  - Interaural time coincidence detectors are present at birth: evidence from
      binaural interaction.
AB  - Binaural processing of sounds in mammals is presumably initiated within the
      auditory nuclei of the caudal pons. The binaural difference waveform (BD) can be
      derived from the sum of the waveforms evoked by right monaural clicks plus left
      monaural clicks minus the waveform evoked by binaural clicks. In adults, the BD's
      first positive peak (beta) is large only for stimuli with interaural time
      differences (ITDs) that produce a fused acoustic percept. Humans at birth can
      localize and discriminate sound sources, but their head circumference is about
      two-thirds of an adult head. In order to test whether beta is related to head
      circumference, we recorded beta in human neonates as a function of ITD. Binaural
      clicks with ITDs ranging between 0 and 1000 micros were used to derive BD
      waveforms in 34 neonates. For ITD=0, beta was detectable in 56% of newborns. The
      incidence of beta detection then decreased as ITD increased. Only 9% of the
      babies had detectable beta for all ITDs. No correlation was found between the
      existence of beta and other properties of the monaural or binaural auditory
      brainstem response. The finding that for some infants beta was present for all
      ITDs up to 1.0 ms suggests that there is no recalibration of brainstem delay
      lines with head growth. Our data suggest that the brainstem auditory pathway for
      detecting interaural time differences in the adult is probably present at birth.
      Maturational factors such as increased myelination and greater firing synchrony
      probably improve the detectability of beta with age. The second peak in the BD
      waveform (delta) was highly correlated with the existence of wave VI in the
      binaural and monaural waveforms.

PMID- 14698089
TI  - Effects of reverberation on fusion of lead and lag noise burst stimuli.
AB  - The purpose of this investigation was to determine the effects of reverberation
      on the precedence effect by obtaining thresholds for perception of leading and
      lagging noise burst stimuli as separate auditory events. In Experiment 1, lag
      burst thresholds for 4-ms noise bursts were measured in a simulated reverberant
      and anechoic environment for nine subjects with normal hearing at presentation
      levels of 10, 20, and 30 dB SL. Results indicated that lag burst thresholds
      obtained in the reverberant environment were higher than those obtained in the
      anechoic environment, with no effect of sensation level. In Experiment 2, three
      new stimulus conditions, two monaural and one binaural control, were employed.
      For one monaural condition, the stimuli were equal in level and for the other,
      the leading stimulus was more intense than the lagging stimulus. For the binaural
      control condition, the stimuli were presented from a perceived spatial location
      of 0 degrees azimuth. In the monaural and binaural control conditions, lag burst
      thresholds were lower than those obtained in the reverberant environment of
      Experiment 1. There was no difference between lag burst thresholds obtained in
      either environment for the monaural and binaural control conditions compared to
      the anechoic condition of Experiment 1. Results of Experiment 2 indicate that the
      higher lag burst thresholds observed in Experiment 1 are not fully explained by a
      peripheral masking effect.

PMID- 14698090
TI  - A normative study of tympanic membrane motion in humans using a laser Doppler
      vibrometer (LDV).
AB  - Laser Doppler vibrometry was used to measure the sound-induced tympanic membrane
      (TM) velocity, assessed near the umbo, in 56 normal hearing human subjects at
      nine sound frequencies. A second series of measurements was made in 47 subjects
      with sensorineural hearing loss (SNHL). Each set of measurements has features in
      common with previously published results. The measured velocity magnitude
      (normalized by the stimulus sound pressure) at any one frequency ranged among
      subjects by factors of 3-0.3 (+/-10 dB) from the mean and the phase angle of the
      normalized velocity ranged from +/-15 degrees around the mean at low frequencies
      to more than +/-200 degrees around the mean at 6 kHz. Measurements repeated after
      intervals of minutes to months were generally within 40% in magnitude (+/-3 dB)
      and 20 degrees in phase. Sources of variability included the effect of small
      differences in the location of the measurement on the TM and small static middle
      ear pressures. No effects of stimulus level, ear sidedness (right or left),
      gender, age or the presence or absence of SNHL were found. These results provide
      a baseline normal response for studies of TM velocity with conductive hearing
      losses of different etiologies.

PMID- 14698091
TI  - Semicircular canal fenestration - improvement of bone- but not air-conducted
      auditory thresholds.
AB  - Auditory stimulation can, under certain circumstances, activate the vestibular
      end organs and this is facilitated by fenestration of a semicircular canal (SCC).
      Several fenestrated profoundly deaf patients reported improvements in their bone-
      (BC) but not air-conducted (AC) thresholds. Bone conduction auditory thresholds
      have been reported to be better than normal in several patients with thinning or
      absence of bone over a SCC (dehiscence). This phenomenon was carefully studied in
      the fat sand rat (Psammomys obesus) by recording auditory brainstem evoked
      responses to BC and AC auditory stimulation, before and after SCC fenestration.
      Fenestration would be expected to decrease the pressure difference across the
      cochlear partition, causing a reduction in the amplitude of the classical base to
      apex input traveling wave, and should therefore lead to an elevation in AC and BC
      thresholds. Instead, BC thresholds decreased (i.e. improved) following
      fenestration (by 7.0+/-4.2 dB; P<0.005), while AC thresholds did not change. Thus
      the cochlea becomes more sensitive to BC, but not AC, stimulation in the presence
      of a SCC fenestration. This may be due to the removal by the fenestration of a
      factor impeding BC cochlear responses, or by the addition of a facilitating
      factor. The result that the SCC fenestration did not affect AC threshold provides
      support for the concept that at low intensities the outer hair cells are directly
      activated by components of the fluid pressures surrounding them, which alternate
      at audio-frequencies. These cochlear fluid audio-frequency pressures are induced
      by stapes footplate movement and not by a base to apex input traveling wave. The
      audio-frequency pressures would not be affected by SCC fenestration. The outer
      hair cell motility thus induced somehow excites the inner hair cells and the
      auditory nerve fibers. At low intensities the outer hair cell motility causes
      localized displacement at the appropriate position on the basilar membrane.

PMID- 14698092
TI  - Immunocytochemical distribution of Met-enkephalin-Arg6-Gly7-Leu8 (Met-8) in the
      auditory system of the rat.
AB  - Methionine-enkephalin-Arg(6)-Gly(7)-Leu(8) (Met(8)) is known to act as a
      neurotransmitter or neuromodulator and it has been implicated in pain,
      cardiovascular and motor mechanisms, but its role in audition is currently
      unknown. In the present study we have applied an immunocytochemical technique and
      describe the distribution of cell bodies and fibers containing Met(8) in the
      auditory pathway of the rat. The main finding is that we found either Met(8)
      immunoreactive fibers or cell bodies or both in virtually all nuclei of the rat
      auditory system except for the medial superior olive and the ventral division of
      the medial geniculate body in which we did not find any immunoreactivity for
      Met(8). This suggests that the neuropeptide Met(8) is widely distributed
      throughout the auditory system of the rat. Our results suggest that Met(8) could
      play at least two roles in hearing. It seems to be involved in the processing of
      the descending auditory pathway, and it may be implicated in the multisensory
      integration of auditory information that takes place in the non-lemniscal
      auditory pathway.

PMID- 14698093
TI  - Dopaminergic olivocochlear neurons originate in the high frequency region of the
      lateral superior olive of guinea pigs.
AB  - Dopaminergic neurons are known to exist within the lateral superior olive (LSO).
      The LSO is the nucleus of origin of the lateral olivocochlear neurons, which
      project to the cochlea and synapse onto the primary afferents contacting the
      inner hair cells. We investigated whether the dopaminergic neurons in the LSO are
      part of the lateral olivocochlear neuron population. We combined intracochlear
      injections of a fluorescent retrograde tracer with immunofluorescent staining of
      tyrosine hydroxylase (TH). TH was used as a marker for dopaminergic neurons.
      After the injection with retrograde tracer most of the TH-labelled neurons in the
      LSO also contained the tracer, which directly demonstrates for the first time
      that the TH-labelled, dopaminergic neurons in the LSO are lateral olivocochlear
      neurons. TH-labelled neurons were not equally distributed over the LSO as is
      observed for the lateral olivocochlear neurons in general. TH-labelled neurons
      were almost exclusively seen in the medial, high frequency, limb of the LSO.
      Since the projection of the lateral olivocochlear neurons to the cochlea is known
      to be tonotopic, we investigated the TH-labelling in the cochlea as well. We
      found that the staining pattern of TH in the cochlea is in broad agreement with
      the distribution of TH-labelling in the LSO. Cochlear sections showed dense
      labelling in the basal and second, high frequency, turns and decreasing intensity
      of staining in the third turn, while the extreme apical, low frequency, turn was
      almost devoid of any positive TH-labelling. These observations imply that the
      dopaminergic neurons of the lateral olivocochlear system may play a role in the
      selective suppression of the high frequency fibers of the auditory system.

PMID- 14698094
TI  - Co-administration of kanamycin and ethacrynic acid as a deafening method for
      acute animal experiments.

PMID- 14698095
TI  - Freezing: an underutilized food safety technology?
AB  - Freezing is an ancient technology for preserving foods. Freezing halts the
      activities of spoilage microorganisms in and on foods and can preserve some
      microorganisms for long periods of time. Frozen foods have an excellent overall
      safety record. The few outbreaks of food-borne illness associated with frozen
      foods indicate that some, but not all human pathogens are killed by commercial
      freezing processes. Freezing kills microorganisms by physical and chemical
      effects and possibly through induced genetic changes. Research is needed to
      better understand the physical and chemical interactions of various food matrices
      with the microbial cell during freezing and holding at frozen temperatures. The
      literature suggests that many pathogenic microorganisms may be sublethally
      injured by freezing, so research should be done to determine how to prevent
      injured cells from resuscitating and becoming infectious. Studies on the genetics
      of microbial stress suggest that the induction of resistance to specific stresses
      may be counteracted by, for example, simple chemicals. Research is needed to
      better understand how resistance to the lethal effect of freezing is induced in
      human pathogens and means by which it can be counteracted in specific foods.
      Through research, it seems possible that freezing may in the future be used to
      reliably reduce populations of food-borne pathogens as well as to preserve foods.

PMID- 14698096
TI  - Flavours of cheese products: metabolic pathways, analytical tools and
      identification of producing strains.
AB  - Aroma development in cheese products results from the metabolic activities of
      cheese bacteria, by glycolysis, lipolysis and proteolysis. To respond to the
      increasing demand for products with improved aroma characteristics, the use of
      bacterial strains for cheese ripening with enhanced flavour production is seen as
      promising. In this review, the catabolism of amino acids, presumably the origin
      of some major aroma compounds, is discussed. The techniques of detection of
      flavour-producing strains are then presented. Their detection may be achieved
      either by genotyping, by enzymatic analysis, or by physico-chemical analysis such
      as HPLC, TLC, GC, and electronic nose.

PMID- 14698097
TI  - Inhibition of Listeria monocytogenes by enterocin EJ97 produced by Enterococcus
      faecalis EJ97.
AB  - Enterocin EJ97 from Enterococcus faecalis EJ97 showed a concentration-dependent
      antimicrobial activity against Listeria monocytogenes CECT 4032. Activity of
      enterocin EJ97 against L. monocytogenes CECT 4032 increased slightly at 4 degrees
      C, and cold-adapted cells did not show any increased resistance. Sensitivity of
      L. monocytogenes CECT 4032 to enterocin EJ97 was not modified by the addition of
      sodium benzoate, sodium acetate, NaCl or sodium tripolyphosphate. Anti-listeria
      activity was enhanced by potassium nitrate, and especially by sodium nitrite at
      concentrations of 50 microg/ml or above. E. faecalis EJ97 produced bacteriocin
      activity during cocultivation with L. monocytogenes CECT 4032 at 37 degrees C and
      also at 15 degrees C, but not at 4 degrees C. Growth of L. monocytogenes CECT
      4032 was inhibited by bacteriocin produced during cocultivation at 37 and 15
      degrees C, and the degree of inhibition was influenced by the incubation
      temperature and the initial concentrations of enterococci and listeria. E.
      faecalis EJ97 also produced bacteriocin during cocultivation in half-skimmed
      milk, although its capacity to control L. monocytogenes was limited to
      populations of 10(3) CFU/ml or lower.

PMID- 14698098
TI  - Considering the complexity of microbial community dynamics in food safety risk
      assessment.
AB  - The potential for competitive inhibition to limit the growth of microbial
      pathogens in food raises questions about the external validity of typical
      predictive microbiology studies and suggests the need to consider microbial
      community dynamics in food safety risk assessment. Ecological theory indicates,
      however, that community dynamics are highly complex and may be very sensitive to
      initial conditions and random variation. Seemingly incongruous empirical results
      for Escherichia coli O157:H7 in ground beef are shown to be consistent with a
      simple theoretical model of interspecific competition. A potential means of
      incorporating community-level microbial dynamics into the food safety risk
      assessment process is explored.

PMID- 14698099
TI  - The presence of Penicillium and Penicillium mycotoxins in food wastes.
AB  - A total of 97 samples (48 summer and 49 winter) of food waste from private
      households were investigated for Penicillium and for mycotoxins. Twenty-five
      Penicillium species were isolated and Penicillium crustosum, Penicillium
      brevicompactum, Penicillium chrysogenum, Penicillium expansum, Penicillium
      roqueforti, Penicillium spinulosum, Penicillium viridicatum, Penicillium commune,
      Penicillium citrinum and Penicillium solitum were, in decreasing order, the most
      frequently identified species. Mycotoxins produced by several of these species,
      including mycophenolic acid, roquefortine C, penitrems A-F and thomitrems A and
      E, were detected. Of the 48 summer samples, 36 were severely infected and
      contained more than 10(5) colony forming units (CFU) Penicillium/g sample. The
      levels of mycotoxins in these samples were in the range 75-19000 microg/kg
      mycophenolic acid, 40-920 microg/kg roquefortine C, 35-7500 microg/kg penitrem A,
      20-2100 microg/kg thomitrem A and 20-3300 microg/kg thomitrem E. Of the 49 winter
      samples, only one was found to contain mycophenolic acid (4800 microg/kg) and
      roquefortine C (190 microg/kg), and this sample was severely infected with P.
      roqueforti. Thirty samples of food waste collected from the food manufacturing
      industry were also investigated. The number of Penicillium in these samples was
      between 10(5) and 10(6) colony forming units (CFU)/g sample. Seven of these
      samples contained mycophenolic acid ranging from 50 to 600 microg/kg and three of
      these samples also contained roquefortine C in the range 100-250 microg/kg.

PMID- 14698100
TI  - Survival and growth of acid-adapted and unadapted Shigella flexneri in a
      traditional fermented Ghanaian weaning food as affected by fortification with
      cowpea.
AB  - Shigellae are among the major causes of diarrheal diseases in infants and young
      children in developing countries. We conducted a study to determine the effect of
      fermentation of corn and corn/cowpea doughs used to prepare a traditional weaning
      porridge on the survival and growth characteristics of acid-adapted and unadapted
      Shigella flexneri. Porridges were prepared from doughs fermented for 0, 24, and
      48 h at 30 degrees C. Four-strain mixtures of acid-adapted and unadapted S.
      flexneri cells were separately inoculated (10(4)-10(5) and 10(6)-10(7) cfu/ml)
      into porridges made from unfermented (pH 5.74-6.05) and fermented (pH 4.07-4.38)
      doughs. Viability of acid-adapted cells was retained at higher levels in porridge
      made from fermented dough, compared to unfermented dough, regardless of
      composition of the porridge or incubation temperature. Cells inoculated into the
      porridges containing fermented dough were not detected (<1 cfu/ml) within 4 h at
      48 degrees C. Results indicate that prior exposure of cells to acid stress
      renders them more resistant to subsequent acidic conditions. The addition of
      cowpea flour to corn dough followed by fermentation had little effect on the
      survival of S. flexneri in porridges made from the dough.

PMID- 14698101
TI  - Genotyping of starter cultures of Bacillus subtilis and Bacillus pumilus for
      fermentation of African locust bean (Parkia biglobosa) to produce Soumbala.
AB  - Bacillus spp. are the predominant microorganisms in fermented African locust bean
      called Soumbala in Burkina Faso. Ten strains selected as potential starter
      cultures were characterised by PCR amplification of the16S-23S rDNA intergenic
      transcribed spacer (ITS-PCR), restriction fragment length polymorphism of the ITS
      PCR (ITS-PCR RFLP), pulsed field gel electrophoresis (PFGE) and sequencing of the
      968-1401 region of the 16S rDNA. In previous studies, the isolates were
      identified by phenotyping as Bacillus subtilis and Bacillus pumilus. The
      phenotyping was repeated as a reference in the present study. The ITS-PCR and ITS
      PCR RLFP allowed a typing at species level. The PFGE was more discriminative and
      allowed a typing at strain level. Full agreement with the phenotyping was
      observed in all cases. The sequencing of the 16S rDNA allowed the identification
      at species level with an identity from 97% to 100% comparing the sequences to
      those from the GenBank databases. The desired cultures of B. subtilis and B.
      pumilus from African locust bean fermentation were distinguished by ITS-PCR and
      ITS-PCR RLFP from Bacillus cereus and Bacillus sphaericus which sometimes occur
      in the beginning of the fermentation.

PMID- 14698102
TI  - Leuconostoc gelidum and Leuconostoc gasicomitatum strains dominated the lactic
      acid bacterium population associated with strong slime formation in an acetic
      acid herring preserve.
AB  - Spoilage characterised by strong slime and gas formation affected some
      manufacture lots of an acetic-acid Baltic herring (Culpea haerengus membras)
      preserve after few weeks of storage at 0-6 degrees C. The product consisted of
      herring filets in acetic acid marinade containing sugar, salt, allspice and
      carrot slices. Microbiological analyses of the spoiled product showed high lactic
      acid bacterium (LAB) levels ranging from 4.5x10(8) to 2.4x10(9) CFU/g. Yeasts
      were not detected in any of the herring samples. Since LAB contaminants are
      seldom associated with fresh fish, LAB populations associated with marinade
      ingredients (carrots, allspice) were also analyzed. The highest LAB levels
      exceeding 10(7) CFU/g were detected in equilibrium modified atmosphere packaged
      baby carrots whereas the levels detected in the allspice samples did not exceed
      4.3x10(5). A total of 176 randomly selected LAB isolates originating from
      herring, carrot and allspice samples were further identified to species level
      using a 16 and 23S rRNA gene RFLP (ribotyping) database. Leuconostoc gelidum and
      Leuconostoc gasicomitatum strains dominated both in the spoiled herring and
      carrot samples. These species are heterofermentative-producing CO(2) from glucose
      and they also produce dextran from sucrose. Inoculation of some commercial
      herring products with spoilage-associated L. gelidum and L. gasicomitatum strains
      verified that these strains have the capability of producing slime and gas in
      herring preserves although slime formation was not as strong as in the original
      samples. Since L. gelidum and L. gasicomitatum strains were commonly detected in
      carrots, carrot slices used for the fish marinade were considered to be the
      probable source of these specific spoilage organisms.

PMID- 14698103
TI  - Evaluation of a challenge testing protocol to assess the stability of ready-to
      eat cooked meat products against growth of Listeria monocytogenes.
AB  - Challenge testing of ready-to-eat (RTE) foods with Listeria monocytogenes is
      recommended to assess the potential for growth. The present study was undertaken
      to evaluate a protocol for challenge testing applied to RTE cooked meat products.
      In order to choose L. monocytogenes strains with a representative behaviour,
      initially, the variability of the response of multiple L. monocytogenes strains
      of human and food origin to different stress and growth conditions was
      established. The strains were not inhibited in their growth at moderate acid pH
      (5.25) and the four strains tested in particular showed a similar acid-adaptive
      response. Growth of the various strains under four different combined stress
      conditions indicated that no L. monocytogenes strain had consistently significant
      longer or shorter lag phase or higher or lower maximum specific growth rates. The
      effect of choice of strain and history (pre-incubation temperature 7 or 30
      degrees C) on growth of L. monocytogenes under optimum conditions (Brain Heart
      Infusion, BHI) and modified BHI simulating conditions of cooked ham and pate was
      studied. In general, all four L. monocytogenes strains behaved similarly. In BHI,
      no difference in lag phase was observed for the cold-adapted and standard
      inoculum, whereas in BHI adjusted to ham and pate conditions, a ca. 40-h
      reduction of the lag phase was noted for the cold-adapted inoculum. Subsequently,
      microbial challenge testing of L. monocytogenes in modified atmosphere packaged
      sliced cooked ham and pate was performed. A mixed inoculum of four L.
      monocytogenes strains and an inoculum level of ca. 1-10 cfu/g was used. On vacuum
      packed sliced cooked ham, the concentration of 100 cfu/g, the safety limit
      considered as low risk for causing listeriosis, was exceeded after 5 days whereas
      ca. 10(5) cfu/g were obtained after 14 days when also LAB spoilers reached
      unacceptable numbers (ca. 10(7) cfu/g) whether standard or cold-adapted inoculum
      was used. The concentration of sodium lactate determined the opportunities for
      growth of L. monocytogenes in pate. If growth of L. monocytogenes in pate was
      noticed, the threshold of 100 cfu/ml was crossed earlier for the cold-adapted
      inoculum compared to the standard inoculum.

PMID- 14698105
TI  - Extreme medicine.
AB  - Extreme Adj Very high or highest in degree or intensity. Very far, or furthest,
      in any direction, especially out from the centre. Very violent or strong. Not
      moderate; severe.

PMID- 14698104
TI  - High efficiency transformation of Penicillium nalgiovense with integrative and
      autonomously replicating plasmids.
AB  - Penicillium nalgiovense is a filamentous fungus that is acquiring increasing
      biotechnological importance in the food industry due to its widespread use as
      starter culture for cured and fermented meat products. Strains of P. nalgiovense
      can be improved by genetic modification to remove the production of penicillin
      and other potentially hazardous secondary metabolites, to improve its capacity to
      control the growth of undesirable fungi and bacteria on the meat product, and
      other factors that contribute to the ripening of the product in order to get
      safer and better quality foods. Genetic manipulation of P. nalgiovense has been
      limited by the lack of molecular genetics tools that were available for this
      fungus, particularly for "self-cloning" avoiding the use of exogenous DNAs. In
      this article we describe a series of vectors, selectable markers and
      transformation methods that can be used for efficient transformation of P.
      nalgiovense, gene cloning and expression. A uridine auxotrophic P. nalgiovense
      mutant with an inactive pyrG gene has been isolated. The P. nalgiovense wild-type
      pyrG gene was cloned and sequenced, and vectors carrying the gene were shown to
      complement the pyrG mutant. Autonomously replicating plasmids carrying the AMA1
      region from Aspergillus nidulans transformed P. nalgiovense very efficiently;
      these plasmids were shown to be maintained as stable extrachromosomal elements in
      P. nalgiovense and could be rescued in Escherichia coli. The mitotic stability of
      self-replicative AMA1 plasmids in P. nalgiovense was higher than that reported
      for Penicillium chrysogenum.

PMID- 14698106
TI  - SARS: aftermath of an outbreak.

PMID- 14698107
TI  - The Gobi Desert medical kit.

PMID- 14698108
TI  - Wilderness medicine.

PMID- 14698109
TI  - Medicine and space exploration.

PMID- 14698110
TI  - Human reactions to deep-water conditions.

PMID- 14698111
TI  - Cold water immersion: sudden death and prolonged survival.

PMID- 14698112
TI  - High-altitude adaptations.

PMID- 14698113
TI  - Physiological hazards of flight at high altitude.

PMID- 14698114
TI  - Use of amphetamines in the military environment.

PMID- 14698115
TI  - Non-lethal weapons: operational and policy developments.

PMID- 14698116
TI  - Prisoners of war: long-term health outcomes.

PMID- 14698117
TI  - The death penalty.

PMID- 14698118
TI  - Female genital mutilation.

PMID- 14698119
TI  - When clinical medicine collides with religion.

PMID- 14698120
TI  - Tuberculosis treatment in complex emergencies: South Sudan.

PMID- 14698121
TI  - Child labour in India: a health and human rights perspective.

PMID- 14698122
TI  - Medicine for refugees.

PMID- 14698123
TI  - Health care in remote Australian Indigenous communities.

PMID- 14698124
TI  - Health care in indigenous populations: the Xingu Indian park.

PMID- 14698125
TI  - Can famine relief meet health and hunger goals simultaneously?

PMID- 14698126
TI  - The importance of being earnest.

PMID- 14698127
TI  - Treatment of children with severe burns.

PMID- 14698128
TI  - Deafblindness: living with sensory deprivation.

PMID- 14698129
TI  - Brain surgery for epilepsy.

PMID- 14698130
TI  - Olympic medicine.

PMID- 14698131
TI  - Realities of rodeo.

PMID- 14698132
TI  - Health and safety in hostile environments.

PMID- 14698133
TI  - Surviving a disaster.

PMID- 14698134
TI  - Transforming growth factor-beta1 inhibits thrombin activation of endothelial
      cells.
AB  - Transforming growth factor-beta1 (TGF-beta1) is reported to exert both pro- and
      anti-inflammatory effects on the chronic activation of endothelial cells (ECs) in
      vitro by cytokines such as tumour necrosis factor-alpha (TNF-alpha). However, the
      effects of TGF-beta1 on acute inflammatory responses of ECs in vitro (e.g. to
      thrombin) have not been characterised. Pretreatment with TGF-beta1 (10 ng/mL)
      effectively inhibited all the thrombin-stimulated responses in rat aortic
      endothelial cells (RAECs) examined: adhesion and migration of polymorphonuclear
      leukocytes, adhesion of platelets and lymphocytes. Substantial inhibition of
      thrombin stimulation occurred after 30 min of pretreatment with TGF-beta1 and
      maximal inhibition was obtained after 1-20 h of pretreatment. Inhibition by TGF
      beta1 pretreatment for 30 min was not affected by cycloheximide and was therefore
      independent of protein synthesis. Treatment with TGF-beta1 for 20 h did not
      affect the total levels of P-selectin and von Willebrand factor (vWF) in RAECs,
      but reduced thrombin-stimulated recruitment of P-selectin and vWF to the cell
      surface. The data demonstrate that TGF-beta1 exerts a potent anti-thrombin effect
      on ECs, effective after long and short pretreatment times.

PMID- 14698136
TI  - IL-10 haplotypes as possible predictors of spontaneous clearance of HCV
      infection.
AB  - BACKGROUND: In hepatitis C virus infection an inappropriate ratio of pro
      inflammatory and anti-inflammatory cytokines may either determine different
      outcomes of the infection or affect the benefit of antiviral treatment. Given
      that polymorphisms in regulatory regions of cytokine genes influence cytokine
      production, we determined frequency of polymorphisms of IL-10, IFNgamma, and
      TNFalpha genes in HCV-infected patients and healthy controls, and investigated
      their association with either ongoing or cleared HCV infection, or with response
      to treatment. METHODS: Genomic DNA from 270 patients and 145 controls sharing the
      same ethnic background was studied by polymerase chain reaction, restriction
      enzyme digestion, direct sequencing, and microsatellite analysis. RESULTS: The IL
      10 ATA haplotype was more frequent in patients with spontaneous HCV RNA clearance
      (36.0%) than in patients with persistent infection (23%) (p=0.009, p corrected =
      0.036). Neither TNF -308 and -238 polymorphisms nor IFNgamma alleles variability
      were associated with different HCV outcome. However, the combination of ATA
      homozygous state and IFNgamma 119 allele was more frequent in patients with
      spontaneous HCV clearance than in patients with ongoing disease (p=0.012; p
      corrected = 0.048). We could not confirm the reported effect of genetic influence
      on the response to treatment. CONCLUSIONS: Our findings indicate that
      heterogeneity in the promoter region of the IL-10 gene has a role in determining
      a spontaneous favourable outcome of HCV infection.

PMID- 14698135
TI  - Changes in plasma levels of inflammatory cytokines in response to paclitaxel
      chemotherapy.
AB  - BACKGROUND: Flu-like symptoms are common, early transient side effects of
      paclitaxel chemotherapy. We hypothesized that these symptoms may be due to
      release of inflammatory cytokines in response to treatment. The objective of this
      study was to assess changes in plasma levels of interleukin (IL)-1beta, IL-6, IL
      8, IL-10, IL-12, and TNF-alpha during chemotherapy and to correlate these changes
      with musculoskeletal symptoms. METHODS: Ninety patients with breast cancer were
      included; 70 patients received single agent paclitaxel either weekly or every 3
      weeks and 20 received FAC (5-FU, doxorubicin, cyclophosphamide) chemotherapy.
      Fifteen healthy volunteers were included as controls. Cytokines and symptoms were
      measured before starting therapy, on day 3 and on the last day of one treatment
      cycle. RESULTS: At baseline, all subjects had measurable levels of IL-8 but only
      49% had IL-12, 45% had IL-10, 32% had IL-6, and 21% had IL-1beta or TNF-alpha in
      their plasma. There was no difference in baseline cytokine levels between cancer
      patients and the healthy volunteers. Schedule-dependent transient changes in the
      levels of 3 cytokines were observed in the paclitaxel treated patients. In the
      every 3-week paclitaxel group, IL-6 and IL-8 increased whereas in the weekly
      paclitaxel group IL-10 increased significantly compared to baseline. Fatigue and
      flu-like symptoms were also worse on day 3. In the weekly paclitaxel group,
      increase in IL-10 level correlated positively with joint pain (p=0.003). In the
      every 3-week paclitaxel group, increase in IL-8 level correlated positively with
      flu-like symptom (p=0.008). In the FAC-treated group and among the healthy
      volunteers none of these cytokines increased significantly. CONCLUSIONS: Weekly
      paclitaxel induces transient increase in IL-10 levels whereas every 3-week higher
      dose treatments induce IL-8 and IL-6 in the plasma. These changes correlate with
      joint pain and flu-like symptoms.

PMID- 14698137
TI  - Sex steroid-mediated regulation of macrophage/monocyte function in a two-hit
      model of trauma-hemorrhage and sepsis.
AB  - Studies have shown that 17beta-estradiol has salutary effects on immune functions
      after trauma-hemorrhage (TH). It remains unknown, however, whether 17beta
      estradiol has a similar effect in a double-hit model of TH and subsequent sepsis.
      It is also unknown if under those conditions the circulating immune cells
      accurately represent immunological responses occurring in fixed tissues, such as
      the spleen. To study this, pre-castrated mice were hormonally treated and then
      subjected to soft-tissue trauma (i.e. midline laporatomy), hemorrhagic shock (MAP
      35+/-5mmHg for 90 min followed by resuscitation) and 24 h later sepsis was
      induced by cecal ligation and puncture (CLP). Splenic macrophages (SMphi) and
      peripheral blood mononuclear cells (PBMC) were isolated and cultured with LPS.
      5alpha-Dihydrotestosterone-treated mice showed a depressed pro-inflammatory
      cytokine production after TH-sepsis in both SMphi and PBMC. In contrast, the
      17beta-estradiol treated groups showed suppressed pro-inflammatory cytokine
      production in the PBMC population under those conditions. In summary, 17beta
      estradiol was able to prevent immune dysfunction after TH and subsequent sepsis.
      However, the beneficial effects of 17beta-estradiol were limited to tissue-fixed
      Mphi, suggesting compartmentalization of the response. Thus, events occurring in
      the tissue-fixed cells are not necessarily reflected in the circulating PBMC
      population.

PMID- 14698138
TI  - Pretreatment with granulocyte-colony stimulating factor decreases
      lipopolysaccharide-induced interferon-gamma production in mice in association
      with the production of interleukin-18.
AB  - We studied the effects of pretreatment with granulocyte-colony stimulating factor
      (G-CSF) on the production of pro- and anti-inflammatory cytokines induced by
      lipopolysaccharide (LPS). Mice received G-CSF or control saline once a day for 7
      days or once at 1 h before the injection of LPS. Cytokines were measured by
      enzyme-linked immunosorbent assay or antibody-based electrochemiluminescence
      assay and cytokine mRNA was measured by RNAse protection assay. Mice pretreated
      with G-CSF for 7 days before LPS had lower serum levels of LPS-induced interferon
      gamma (IFN-gamma) and higher levels of interleukin (IL)-6 and IL-10 than
      controls. G-CSF-pretreated mice also had lower mRNA levels of IFN-gamma and
      higher mRNA levels of IL-6 and IL-10 in the spleen and/or liver than controls. G
      CSF-pretreated mice had serum levels of tumor necrosis factor, IL-12 p70 and IL
      12 p40 similar to controls. G-CSF-pretreated mice had lower levels of spleen IL
      18 than controls-serum IL-18 being undetectable in mice after LPS-and lower
      levels of IL-18 mRNA in the spleen. Mice pretreated with G-CSF 1 h before LPS had
      lower levels of serum IFN-gamma and spleen IL-18 than controls. G-CSF
      pretreatment alters the expression of LPS-induced cytokines with a decrease in
      pro-inflammatory IFN-gamma and an increase in anti-inflammatory IL-6 and IL-10. G
      CSF decrease of IL-18 production may be a major mechanism explaining the effects
      of G-CSF on the production of IFN-gamma.

PMID- 14698139
TI  - Glial activation and TNFR-I upregulation precedes motor dysfunction in the spinal
      cord of mnd mice.
AB  - Mice homozygous for the spontaneous motor neuron degeneration mutation (mnd) show
      at the age of 8 months a marked impairment of the motor function and accumulation
      of lipofuscin granules in the cytoplasm of almost all neurons of the central
      nervous system. We previously reported a significant increase in GFAP protein
      levels in the lumbar spinal cord homogenates by western blot analysis and
      upregulation of TNF, a proinflammatory cytokine, in the motor neurons of lumbar
      spinal cord of mnd mice, already in a presymptomatic stage (4 months of age). In
      the present study, using immunohistochemical analysis, we performed a time course
      in mnd mice (1, 4 and 9 months of age) evaluating the expression and the
      distribution of astroglial and microglial cells and the expression of both TNF
      receptors, TNFR-I and TNFR-II. We observed a marked increase in astroglial and
      microglial cells and in TNFR-I immunoreactivity already at the 4th month. Since
      motor neuron dysfunction occurs in mnd mice in the absence of evident loss of
      spinal motor neurons, the present results indicate that the activation of
      microglial cells and astrocytes is independent from neuronal degeneration. The
      role of TNF and TNFR-I on motor neurons is still to be demonstrated.

PMID- 14698140
TI  - Stat3-dependent induction of interleukin-3 receptor expression in leukemia
      inhibitory factor-stimulated M1 mouse leukemia cells.
AB  - M1 mouse leukemia cells differentiate to macrophages/monocytes by the stimulation
      of interleukin-6 (IL-6)/leukemia inhibitory factor (LIF). To identify new LIF
      induced genes, we have performed representational difference analysis using M1
      cells and cloned mouse interleukin-3 (IL-3) receptor beta subunit gene. The mRNA
      expression of both IL-3 receptor (IL-3R) alpha and beta subunits is upregulated
      after 1 h stimulation of LIF and remains to be elevated along the differentiation
      of M1 cells. This induction is almost completely suppressed in M1 cells
      expressing a dominant negative form of Stat3. Furthermore, we show that IL-3
      induced Stat5 phosphorylation increases in LIF-stimulated M1 cells. These results
      suggest that Stat3 may play a role in the differentiation of myeloid cells by
      regulating IL-3R expression.

PMID- 14698141
TI  - Electrofusion of syngeneic dendritic cells and tumor generates potent therapeutic
      vaccine.
AB  - Antigen presentation by dendritic cells (DCs) has the potential to elicit
      therapeutic immune responses against malignant tumors. One strategy utilizing DC
      tumor fusion hybrids as cancer vaccine is particularly attractive because of
      polyclonal presentation of a diverse array of unaltered tumor antigens. We have
      recently developed a large-scale electrofusion technique for generating DC-tumor
      heterokaryons and demonstrated their superb immunogenicity. Here, employing the
      weakly immunogenic MCA205 sarcoma, a single vaccination with electrofusion
      hybrids eradicated tumors established in the lung, skin, and brain. Immunotherapy
      required intra-lymphoid vaccine delivery and co-administration of adjuvants such
      as OX-40R antibody. Tumor eradication was immunologically specific and involved
      the participation of both CD4 and CD8 T cells. Consistent with DC's functionality
      of MHC-restriction, the use of syngeneic DCs for fusion was an obligatory
      requirement. Fusion with allogeneic DCs completely lacked therapeutic effects.
      These findings provide a strong impetus for treating cancer patients with
      similarly generated DC-tumor hybrids.

PMID- 14698142
TI  - Identical alpha-chain T-cell receptor transcripts are present on T cells
      infiltrating coronary arteries of human cardiac allografts with chronic
      rejection.
AB  - Chronic cardiac allograft rejection is characterized by graft arteriopathy and is
      a major obstacle of graft survival. We investigated T-cell receptor (TCR) alpha
      chain transcripts of T cells infiltrating human epicardial coronary arteries from
      cardiac allografts with chronic rejection. The non-palindromic adaptor-polymerase
      chain reaction (NPA-PCR) was used to specifically amplify TCR alpha-chain
      transcripts from five explanted cardiac allografts with chronic rejection. The
      amplified products were cloned and sequenced to obtain the entire ValphaJalpha
      region. Immuno-histochemistry was used to identify the mononuclear cell
      infiltrates in the coronary arteries. All the five coronary artery specimens
      exhibited large populations of infiltrating mononuclear cells, which were
      primarily comprised of T cells and macrophages. In three specimens, high
      proportions ( approximately 80%) of identical alpha-chain TCR transcripts were
      detected. In peripheral blood mononuclear cells from a healthy individual, alpha
      chain TCR transcripts were unique when compared to each other. Endomyocardial
      biopsies collected from one patient six months before the allograft was
      explanted, contained identical alpha-chain TCR transcripts to those found to be
      clonally expanded in the coronary arteries from this patient. These results
      indicate that T cells infiltrating the epicardial arteries of cardiac allografts
      with chronic rejection undergo proliferation and clonal expansion in response to
      a specific antigen, which very likely is an (allo)antigen(s).

PMID- 14698143
TI  - Concerted expression of eotaxin-1, eotaxin-2, and eotaxin-3 in human bronchial
      epithelial cells.
AB  - Eotaxin-1/CCL11, eotaxin-2/CCL24, and eotaxin-3/CCL26 bind specifically and
      exclusively to CC chemokine receptor (CCR) 3, which is a potential therapeutic
      target in treating the peribronchial eosinophilia associated with allergic airway
      diseases. Bronchial epithelial cells represent an important source of chemokines,
      and thus we investigated in vitro and in vivo expression of eotaxin-2 and eotaxin
      3 in bronchial epithelial cells in comparison with that of eotaxin-1.
      Immunohistochemistry showed increased expression of both eotaxin-2 and eotaxin-3
      in addition to eotaxin-1 in asthmatics. Considerable amounts of eotaxins were
      secreted by bronchial epithelial lineage. As with eotaxin-1 production,
      generation of eotaxin-2 and eotaxin-3 by bronchial epithelial cells was up
      regulated by IL-4 and IL-13, and attenuated by IFN-gamma and glucocorticoids. In
      addition to eotaxin-1 expression, but also eotaxin-2 and eotaxin-3 expression in
      the bronchial epithelium should be taken into consideration when developing the
      therapeutic strategies to treat eosinophilic airway diseases.

PMID- 14698144
TI  - Activated peripheral T lymphocytes undergo apoptosis when cultured with monocytes
      activated by HLA class II ligation.
AB  - We treated PBMC with anti-MHC class II mAb known to inhibit T lymphocyte
      proliferation. Adherent cells from mAb-treated PBMC showed increased metabolic
      activity by the MTS assay that was not due to cell proliferation. PBMC cultured
      with solid-phase anti-class II mAb in chamber inserts inhibited, across a
      membrane, the proliferation of PBMC cultured with soluble anti-CD3 mAb. PBMC
      treated with both soluble mAb underwent apoptosis as shown by nucleosomal DNA
      fragmentation. The monocytes formed multinucleated giant cells as shown by
      fluorescent microscopy, and contained apoptotic bodies as shown by the TUNEL
      method and by electron microscopy. The apoptotic cells were identified as T cells
      by double-staining with anti-CD4/CD8-PE and annexin-V-FITC. Thus, MHC class II
      ligation stimulates monocytes to increase their metabolic activity, induce
      apoptosis of activated T lymphocytes, and phagocytize the apoptotic cells. TCR
      mediated ligation of MHC class II may play a role in the downregulation of immune
      responses.

PMID- 14698145
TI  - CD8+ T-cell mediated anti-tumor responses cross-reacting against 9L and RT2 rat
      glioma cell lines.
AB  - We have shown that vaccination of animals with two distinct commonly used glioma
      cell lines, 9L and RT2, generated cross-reactive cellular anti-tumor immunity.
      Peripheral vaccination with either cell line 9L or RT2 resulted in MHC Class I
      restricted effector cells capable of in vitro cytolytic activity against both
      target 9L and RT2 cells but not the syngeneic F98 glioma cell line. In vitro
      cross-reactive cytolytic activity could be measured for as long as 6 months from
      the time of initial vaccination. Fractionation of splenic effector cells revealed
      the cytolytic activity to be CD8+ T-cell mediated but required CD4+ T-cells for
      effective antigen presentation. Anti-tumor immunity generated after vaccination
      with either 9L or RT2 was completely protective against subsequent subcutaneous
      inoculation of animals with either 9L or RT2 cells and resulted in prolonged
      survival in animals inoculated intracranially with either cell line. Our results
      suggest that despite the different methods used in their derivation, 9L and RT2
      glioma cells share a common glioma antigen recognized by the cellular arm of the
      immune response.

PMID- 14698147
TI  - Synthesis of potent and selective 2-azepanone inhibitors of human tryptase.
AB  - The serine protease tryptase has been associated with a broad range of allergic
      and inflammatory diseases and, in particular, has been implicated as a critical
      mediator of asthma. The inhibition of tryptase therefore has the potential to be
      a valuable therapy for asthma. The synthesis, employing solution phase parallel
      methods, and SAR of a series of novel 2-azepanone tryptase inhibitors are
      presented. A member of this series, 8t, was identified as a potent inhibitor of
      human tryptase (IC(50)=38 nM) with selectivity >/=330-fold versus related serine
      proteases (trypsin, plasmin, uPA, tPA, APC, alpha-thrombin, and FXa) [corrected].

PMID- 14698146
TI  - The chemokine CX3CL1 regulates NK cell activity in vivo.
AB  - In vitro, chemokines can both activate and induce migration of NK cells. However,
      little is known about how chemokines influence NK cell activity in vivo. We
      studied the role of CX(3)CL1 and its receptor, CX(3)CR1, in modulating NK cell
      activity in an established in vivo model of tumour cell clearance. Radiolabelled
      YAC-1 target cells intravenously injected into C57BL/6 mice rapidly localize to
      the lungs and are cleared by NK cells. In mice pre-treated with blocking anti
      CX(3)CL1 or anti-CX(3)CR1 Ab, target cell clearance decreased by four- to
      fivefold (p<0.001). In vitro, we found no effect of anti-CX(3)CL1 or anti
      CX(3)CR1 Ab on NK lysis of target cells. We further examined adhesion of NK cells
      to Py-4-1 endothelial cells. NK cell binding to activated endothelial monolayers
      was significantly inhibited by anti-CX(3)CR1 Ab or soluble CX(3)CL1 (p<0.001).
      These studies identify a critical role for CX(3)CL1 in modulating NK cell
      activity in vivo.

PMID- 14698148
TI  - 4,5-Disubstituted-1,3-oxazolidin-2-imine derivatives: a new class of orally
      bioavailable nitric oxide synthase inhibitor.
AB  - In our search for a novel class of inducible nitric oxide synthase (iNOS)
      inhibitors, 1,3-oxazolidin-2-imine was found to weakly inhibit iNOS. Further
      modifications of this compound resulted in a remarkable increase in both the in
      vivo and in vitro inhibitory activity and selectivity for iNOS.

PMID- 14698149
TI  - Parallel solid-phase synthesis of disubstituted (5-biphenyltetrazolyl) hydantoins
      and thiohydantoins targeting the growth hormone secretagogue receptor.
AB  - An efficient solid-phase protocol for the synthesis of substituted (5
      biphenyltetrazolyl)-hydantoins and -thiohydantoins has been developed. Suzuki
      cross-coupling between resin-bound 2-(tetrazol-5-yl)-phenylborinane and 4
      bromobenzaldehyde gave the corresponding tetrazolylbiphenyl aldehyde. Subsequent
      reductive amination using amino acid esters gave the pivotal resin bound amino
      acid esters which were transformed to hydantoins or thiohydantoins via two
      routes: (i) treatment with isocyanates or isothiocyanates or (ii) successive
      treatment with triphosgene and primary amines. Using molecular modeling, we were
      able to jump from L-692,429, a well known non-peptidyl growth hormone
      secretagogue (GHS), to biphenyltetrazolyl hydantoins, obtaining compounds with
      IC(50) values below 600 nM after two iterative cycles only.

PMID- 14698150
TI  - Pyridazines. Part 36: Synthesis and antiplatelet activity of 5-substituted-6
      phenyl-3(2H)-pyridazinones.
AB  - A convenient and efficient palladium-catalysed retro-ene-assisted method has been
      developed to prepare a series of 5-substituted-6-phenyl-3(2H)-pyridazinones as
      potential antiplatelet drugs. The most active compounds were those that contain a
      3-phenyl-3-oxo-propenyl fragment or a phenylthio group at position 5 of the
      heterocyclic ring.

PMID- 14698151
TI  - Adenine derived inhibitors of the molecular chaperone HSP90-SAR explained through
      multiple X-ray structures.
AB  - Multiple co-crystal structures of an adenine-based series of inhibitors bound to
      the molecular chaperone Hsp90 have been determined. These structures explain the
      observed SAR for previously described compounds and new compounds, which possess
      up to 8-fold improved potency against the isolated enzyme. Anti-tumour cell
      potency and mechanism of action data is also described for the most potent
      compounds. These data should enable the design of more potent Hsp90 inhibitors.

PMID- 14698152
TI  - Synthesis of galactopyranosyl amino alcohols as a new class of antitubercular and
      antifungal agents.
AB  - The galactopyranosyl amino alcohols (3-16) were synthesised by regioselective
      oxirane ring opening of compound 2 with variety of amines and screened for
      antitubercular and antifungal activities. One of the compounds (16) showed potent
      activity against Mycobacterium tuberculosis H37 Rv in vitro and also displayed
      activity in MDR TB. The compound (16) was found to be superior to ethambutol
      clinically used anti TB drug in in vitro screen.

PMID- 14698153
TI  - Imidazole derivatives as new potent and selective 20-HETE synthase inhibitors.
AB  - In a previous paper, we reported that an imidazole derivative 1 exhibited a
      potent inhibitory activity of 20-HETE synthase (1; IC(50) value of 5.7 nM), but
      this compound also exhibited little selectivity for cytochrome P450s (CYPs). We
      examined some derivatives of imidazole 1 which had an amino group on the side
      chain, and found that a dimethylaminohexyloxy derivative (3g; IC(50) value of 8.8
      nM) showed potent and selective inhibitory activity.

PMID- 14698154
TI  - Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of
      human isozyme II with the antipsychotic drug sulpiride.
AB  - The X-ray crystal structure for the adduct of human carbonic anhydrase (hCA) II
      with sulpiride, a sulfonamide derivative clinically used as antipsychotic drug,
      has been resolved at a resolution of 1.6 A. This compound is an effective
      inhibitor of the physiologically most relevant isozyme hCA II (K(i) of 40 nM),
      being only a moderate or moderate-weak inhibitor of the cytosolic isozyme hCA I
      (K(i) of 1200 nM) and the membrane-bound isozyme hCA IV (K(i) of 620 nM).
      Sulpiride shows CA inhibitory properties of the same magnitude as
      dichlorophenamide, a clinically used antiglaucoma sulfonamide, or valdecoxib, a
      COX-2 selective inhibitor recently shown to inhibit CA. The binding of sulpiride
      to the hCA II active site is similar to that of other sulfonamide inhibitors,
      considering the interactions of the sulfonamide zinc anchoring group, but differs
      considerably when the organic scaffold of the molecule is analyzed. Indeed, one
      unprecedented hydrogen bond involving the imino moiety of the carboxamido group
      of sulpiride and a water molecule was observed, together with a unique stacking
      interaction of the N-methyl-pyrrolidine ring of the inhibitor and the aromatic
      ring of Phe 131 of the enzyme active site, which has been observed only recently
      in another CA-sulfonamide complex.

PMID- 14698155
TI  - Synthesis and evaluation of indenopyrazoles as cyclin-dependent kinase
      inhibitors. Part 4: Heterocycles at C3.
AB  - New indeno[1,2-c]pyrazol-4-one cyclin dependent kinase inhibitors have been
      disclosed. The most promising compounds are nanomolar enzyme inhibitors with
      excellent activity against tumor cells. The most advanced compound retains cell
      culture activity even in the presence of human serum proteins. The most advanced
      compound did not kill the normal fibroblast line AG1523.

PMID- 14698156
TI  - Triaryl methane derivatives as antiproliferative agents.
AB  - Clotrimazole (CLT) 1, a synthetic anti-fungal imidazole derivative, inhibits
      tumor cell proliferation and angiogenesis. In the current study, flow cytometric
      analysis demonstrated that the decrease in tumor cell growth by CLT 1 was
      associated with inhibition of cell cycle progression at the G(1)-S phase
      transition, resulting in G(0)-G(1) arrest. A series of CLT 1 analogues has been
      generated in order to develop CLT 1 derivatives that are devoid of the imidazole
      moiety which is responsible for the hepatoxicity associated with CLT 1 while
      retaining CLT 1 efficacy. The majority of these analogues demonstrate in vitro
      antiproliferative activity ranging from submicromolar to micromolar
      concentrations.

PMID- 14698158
TI  - A novel Pd-catalyzed cyclization reaction of ureas for the synthesis of
      dihydroquinazolinone p38 kinase inhibitors.
AB  - A series of potent p38 inhibitors based on the dihydroquinazoline scaffold was
      synthesized using a novel Pd-catalyzed cyclization reaction of aryl-benzyl ureas.
      Optimization of this compound class led to compound 20, which inhibits p38alpha
      in vitro with IC(50)=14 nM and is active in the mouse TNFalpha-release model.

PMID- 14698159
TI  - Synthesis and evaluation as sialidase inhibitors of xylo-configured
      cyclohexenephosphonates carrying glycerol side-chain mimics.
AB  - Based on a strategy previously reported by us, we have synthesized D-xylo
      configured cyclohexenephosphonates designed to mimic the transition state of the
      sialidase reaction. The double bond orientation corresponds to the benchmark
      inhibitor Neu5Ac2en and we could selectively introduce hydroxyalkyl substituents
      in order to simulate the glycerol side-chain of neuraminic acid. The inhibitory
      activity of a set of compounds towards bacterial sialidases was tested and
      interesting differences in activity were found.

PMID- 14698157
TI  - Optimization of the indolyl quinolinone class of KDR (VEGFR-2) kinase inhibitors:
      effects of 5-amido- and 5-sulphonamido-indolyl groups on pharmacokinetics and
      hERG binding.
AB  - Modifications to the basic side-chain of early lead structures of the indolyl
      quinolinone class of KDR kinase inhibitors resulted in improved pharmacokinetic
      and ancillary profiles. Specifically, compounds bearing 5-amido- and 5
      sulphonamido-indolyl substituents exhibited lower plasma clearance and weaker
      binding affinity for the I(Kr) potassium channel hERG.

PMID- 14698160
TI  - Covalent binding of the 13C-labeled skin sensitizers 5-chloro-2-methylisothiazol
      3-one (MCI) and 2-methylisothiazol-3-one (MI) to a model peptide and glutathione.
AB  - The reactivity of 4-[13C]- and 5-[13C]-5-chloro-2-methylisothiazol-3-one (MCI)
      and 2-methylisothiazol-3-one (MI) towards a model peptide and glutathione was
      followed by 13C and 1H[13C] NMR spectroscopy. Both molecules were found to react
      with GSH but in addition MCI was found to react with histidine and lysine to form
      adducts of a different nature. Reaction with histidine led to stable substitution
      adducts through an addition-elimination reaction at position 5 while reaction
      with lysine led to the formation of open adducts of the thioamide or amide type.

PMID- 14698161
TI  - Synthesis and biological characterisation of [3H]BBL454, a new CCK2 selective
      radiolabelled agonist displaying original pharmacological properties.
AB  - [(3)H]BBL454, a new CCK(2) selective tritiated agonist was prepared via the
      reductive tritiation of a 5-aminopentyn-1-yl moiety introduced on the N-terminal
      end of a pentapeptide derivative of cholecystokinin. The binding properties of
      this labelled compound were determined on CHO cells transfected with the rat
      CCK(2) receptor. [(3)H]BBL454 is able to discriminate two affinity states of the
      CCK(2) receptor a supplementary indication of its validity for further exploring
      the heterogeneity of this receptor.

PMID- 14698162
TI  - Acetylene-based analogues of thiolactomycin, active against Mycobacterium
      tuberculosis mtFabH fatty acid condensing enzyme.
AB  - Analogues of the natural antibiotic thiolactomycin, with acetylene-based side
      chains, have the highest recorded in vitro inhibitory activity against the
      recombinant Mycobacterium tuberculosis beta-ketoacyl-ACP synthase mtFabH
      condensing enzyme. In particular, 5-[3-(4-acetyl-phenyl)-prop-2-ynyl]-4-hydroxy
      3,5-dimethyl-5H-thiophen-2-one exhibited more than an 18-fold increased potency,
      compared to thiolactomycin, against this key condensing enzyme, involved in M.
      tuberculosis mycolic acid biosynthesis. Analogues of the antibiotic
      thiolactomycin, with acetylene-based side chains, have the highest recorded
      activity against cloned mtFabH condensing enzyme.

PMID- 14698163
TI  - Synthesis of novel melanocortin 4 receptor agonists and antagonists containing a
      succinamide core.
AB  - A novel series of piperazines appended to a succinamide backbone were synthesized
      and found to have a high affinity for the melanocortin-4 receptor (IC(50)s
      ranging from <0.1 to 200 nM). Both agonists and antagonists of MC4R were prepared
      by modifying the groups attached to the right-hand side of the succinamide. This
      series also exhibits a high level of selectivity (up to 7000-fold) over mouse
      MC1R and human MC3R.

PMID- 14698164
TI  - Synthesis and biological evaluation of nonpeptide integrin antagonists containing
      spirocyclic scaffolds.
AB  - Analogues of isoxazoline alpha(v)beta(3) antagonist 1 designed to further
      restrict the four carbon alkyl tether were prepared by incorporating two
      spirocyclic scaffolds, 1-oxa-2-azaspiro[4,5]dec-2-ene and 1-oxa-2,7
      diazaspiro[4,4]non-2-ene. Additional optimization provided potent antagonists of
      both alpha(v)beta(3) and alpha(5)beta(1) which are selective over GPIIb/IIIa.

PMID- 14698165
TI  - Discovery of novel PTP1b inhibitors.
AB  - A small library of 19 compounds was designed based on unique structural features
      of PTP1b. Utilizing electrospray ionization mass spectrometry (ESI-MS) to provide
      binding information about complexes of enzyme and small molecule ligands, two
      classes of lead compounds were discovered.

PMID- 14698166
TI  - Synthesis and antibacterial activity of 7-(substituted)aminomethyl quinolones.
AB  - A series of 7-(substituted)aminomethyl quinolones was synthesized and evaluated
      for antibacterial activity. Derivatives with (monoalkyl)aminomethyl substituent
      at C-7 displayed high in vitro activities comparable to Lomefloxacin against gram
      negative organisms, whereas those bearing a [(substituted)phenyl]aminomethyl side
      chain at C-7 demonstrated good activities against gram-positive organisms as
      potent as Lomefloxacin and Vancomycin.

PMID- 14698167
TI  - Design and synthesis of novel cyanoguanidine ATP-sensitive potassium channel
      openers for the treatment of overactive bladder.
AB  - Thiourea derivatives were identified as glyburide-reversible potassium channel
      openers through high-throughput screening. Based on these findings, a number of
      novel cyanoguanidines were designed and synthesized, which hyperpolarized human
      bladder K(ATP) channels. These agents are potent full agonists in relaxing
      electrically-stimulated pig bladder strips. The synthesis, SAR and biological
      properties of these agents are discussed.

PMID- 14698168
TI  - Binding of a homologous series of anthraquinones to DNA.
AB  - The DNA binding characteristics of a series of homologous 2,6-disubstituted
      anthraquinone threading intercalators bearing one to four ethylene glycol units
      in their side chains have been studied. Binding constants were measured via
      surface plasmon resonance (SPR). These compounds bind to an AT-rich hairpin with
      slightly higher affinity than to a GC-rich hairpin. The binding constants
      decrease as the length of the side chain increases.

PMID- 14698169
TI  - N-Benzylindole-2-carboxylic acids: potent functional antagonists of the CCR2b
      chemokine receptor.
AB  - Screening of the corporate database led to the discovery of a novel series of N
      benzylindole-2-carboxylic acid CCR2b chemokine receptor antagonists. These
      compounds demonstrate high affinity and functional inhibition of the CCR2b
      receptor. A discussion of the structure-activity relationships is presented,
      together with evidence for a highly selective receptor binding profile.

PMID- 14698170
TI  - A novel series of potent and selective IKK2 inhibitors.
AB  - A novel series of aminopyrimidine IKK2 inhibitors have been developed which show
      excellent in vitro inhibition of this enzyme and good selectivity over the IKK1
      isoform. The relative potency and selectivity of these compounds has been
      rationalized using QSAR and structure-based modelling.

PMID- 14698171
TI  - 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta.
AB  - Kenpaullone derivatives with a modified parent ring system were synthesized in
      order to develop kinase inhibitors with enhanced selectivity. Among the novel
      structures, 1-azakenpaullone was found to act as a selective GSK-3beta versus
      CDK1 inhibitor. The charge distribution within the 1-azakenpaullone molecule is
      discussed as a possible explanation for the enhanced GSK-3beta selectivity of 1
      azakenpaullone compared to other paullone derivatives.

PMID- 14698172
TI  - Aspermytin A: a new neurotrophic polyketide isolated from a marine-derived fungus
      of the genus Aspergillus.
AB  - A new polyketide, aspermytin A (1), was isolated from a cultured marine fungus,
      Aspergillus sp., which was separated from the mussel, Mytilus edulis. Its
      structure was elucidated on the basis of their spectral data, and the absolute
      configuration of 1 was determined by the CD spectrum. Aspermytin A induced
      neurite outgrowth in rat pheochromocytoma (PC-12) cells at concentration of 50
      microM.

PMID- 14698173
TI  - Inhibition of angiogenesis by THAM-derived cotelomers endowed with thalidomide
      moieties.
AB  - The synthesis of a tris(hydroxymethyl)acrylamidomethane (THAM)-derived cotelomer
      endowed with thalidomide units and a preliminary assessment of its biological
      activity are described. 4-Carboxy thalidomide and 4-(N-acryloyl) lysine
      thalidomide derivatives were prepared. The polymerization of these compounds with
      THAM in the presence of octanethiol as transfer reagent provided a water-soluble
      telomer bearing several thalidomide units. The ability of this telomer to inhibit
      angiogenesis in a mouse model of corneal neovascularization was compared to 4
      carboxy thalidomide and thalidomide. A significant inhibition in area of
      neovascularization stimulated by a bFGF pellet was observed only in the mice
      treated with the telomer.

PMID- 14698174
TI  - A novel protein crosslinking reagent for the determination of moderate resolution
      protein structures by mass spectrometry (MS3-D).
AB  - A new approach to the determination of moderate resolution protein structures,
      termed MS3-D-Mass Spectrometry in 3 Dimensions-has recently been disclosed. The
      method involves the formation of covalent crosslinks between reactive residues on
      the protein surface, the determination of the location of those crosslinks in
      primary sequence space by mass spectrometry, and then the imposition of a
      distance constraint upon the location of the respective side chains during
      distance geometry calculations of protein structure. MS3-D is rapid, requires
      small amounts of protein, and works in native biochemical conditions. Therefore,
      it offers the potential for determination of the structures of all proteins
      expressed by an organism in a high throughput manner. However, the methodology is
      completely dependent upon the production of chemical crosslinks and technical
      limitations of available crosslinkers have proven problematic in generalization
      and automation of the method for the determination of the structures of complete
      proteomes. Presented herein is the design, synthesis, and proofing of a novel
      modular protein crosslinking reagent designed to enhance hydrophilicity, provide
      an increased effective signal to noise ratio for MS3-D, and allow the sampling of
      a wider variety of side chains during the process.

PMID- 14698175
TI  - Synthesis and pharmacological evaluation of prenylated and benzylated
      pterocarpans against snake venom.
AB  - Edunol (3), a pterocarpan isolated from Harpalyce brasiliana, a plant used in the
      northeast of Brazil against snakebites, was obtained by synthesis and showed
      antimyotoxic, antiproteolytic and PLA2 inhibitor properties. These proprieties
      could be improved through the synthesis of a bioisoster (5), where the prenyl
      group was replaced by the benzyl group.

PMID- 14698176
TI  - Effects of fluorine substitution of cytosine analogues on the binding affinity to
      HIV-1 reverse transcriptase.
AB  - In order to find out the possible role of fluorine substituent in binding of the
      fluorinated cytidine analogues at the active site of HIV-1 RT, binding modes of
      several 5-fluoro cytidine analogues, such as FTC, D-dioxolane 5-FC and D-2'F-d4FC
      to the active site of HIV-1 reverse transcriptase, were compared by molecular
      dynamics studies.

PMID- 14698177
TI  - The solid-phase conjugation of purpurin-18 with a synthetic targeting peptide.
AB  - It has been demonstrated that efficient site-specific coupling of the highly
      active photodynamic therapy sensitiser purpurin-18 to the synthetic targeting
      peptide G-G-V-K-R-K-K-K-P-G-Y-G can be achieved with greater than 85% purity.

PMID- 14698178
TI  - 1,2-Diaryl-1-ethanone and pyrazolo [4,3-c] quinoline-4-one as novel selective
      cyclooxygenase-2 inhibitors.
AB  - Novel 1,2-diaryl-1-ethanone 1 and pyrazolo [4,3-c] quinoline-4-one 2, with
      pharmacophores different from the known COX inhibitors were identified as
      selective COX-2 inhibitors. The communication briefly describes SAR of both the
      series.

PMID- 14698179
TI  - Design, synthesis, and activity of HDAC inhibitors with a N-formyl hydroxylamine
      head group.
AB  - Histone deacetylases (HDAC) are promising targets for cancer chemotherapy. HDAC
      inhibitors are thought to act in part by disrupting normal cell cycle regulation,
      resulting in apoptosis and/or differentiation of transformed cells. Several HDAC
      inhibitors, which contain hydrophobic tails and the Zn(2+) chelator hydroxyamic
      acid as a head group, are potent inhibitors of HDACs both in vitro and in vivo.
      In this study, a related class of compounds with a N-formyl hydroxylamino head
      group has been synthesized and their ability to inhibit HDACs have been assayed
      in biochemical and cellular assays. These compounds were found to have comparable
      activities to suberoylanilide hydroxyamic acid (SAHA) in HDAC enzymatic assays
      and histone hyperacetylation cellular assays.

PMID- 14698180
TI  - 4-Hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives
      as potent anti-tumor agents.
AB  - Based on the structure of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid
      ethyl ester (1), which exhibits selective cytotoxicity against a tumorigenic cell
      line, (2,4-dimethoxyphenyl)-(4-hydroxy-3-methyl-6-phenylbenzofuran-2-yl)
      methanone (18m) was designed and synthesized as a biologically stable derivative
      containing no ester group. Although the potency of 18m was almost the same as our
      initial hit compound 1, 18m is expected to last longer in the human body as an
      anticancer agent.

PMID- 14698181
TI  - Orally active amino functionalized antimalarial 1,2,4-trioxanes.
AB  - Using readily available trioxanes 6a-b, a new series of amino functionalized
      1,2,4-trioxanes 8a-e and 9a-e have been prepared and evaluated for antimalarial
      activity against multi-drug resistant Plasmodium yoelii in Swiss mice model.
      Several of these novel trioxanes are orally more active than the parent trioxanes
      6a-b. Antimalarial activity of amino functionalized trioxane 9a, the most potent
      compound in the series, is very close to that of beta-arteether.

PMID- 14698182
TI  - Syntheses and radical scavenging activities of resveratrol derivatives.
AB  - Nine new resveratrol derivatives, having bromo, iodo, and fluoroethyl groups,
      were designed and synthesized. All compounds having free phenol groups showed
      good free radical scavenging activity. Among them, 2-bromoresveratrol 19 has a
      similar free radical scavenging activity to (+)-catechin.

PMID- 14698183
TI  - Synergistic effect of CMP/KDO synthase inhibitors with antimicrobial agents on
      inhibition of production and release of Vero toxin by enterohaemorrhagic
      Escherichia coli O157:H7.
AB  - Synergistic effect of CMP/KDO synthase inhibitors in LPS biosynthesis of Gram
      negative bacteria with kanamycin (KM) and fosfomycin (FOM) on the production and
      release of Vero toxins (VTs) by Escherichia coli O157 was evaluated in vitro.
      While CMP/KDO synthase inhibitors, KM and FOM showed no inhibitory effect on the
      production/release of VTs by themselves alone, both KM and FOM showed the
      remarkable inhibition of VT2 release through synergistic collaboration with
      CMP:KDO synthase inhibitor.

PMID- 14698184
TI  - Synthesis and antitumour activity of pyrene-linked pyrrolo [2,1-c]benzodiazepine
      hybrids.
AB  - Pyrene-linked pyrrolobenzodiazepine hybrids have been synthesized that exhibit
      potential anticancer activity in a number of human tumour cell lines. These
      hybrids also exhibit much enhanced DNA-binding ability in comparison to the
      parent pyrrolobenzodiazepine ring system (DC-81).

PMID- 14698185
TI  - MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 3:
      Optimization of potency in the pyridopyrimidine series through the application of
      a pharmacophore model.
AB  - The addition of substituents to the pyridopyrimidine scaffold of MexAB-OprM
      specific efflux pump inhibitors was explored. As predicted by a pharmacophore
      model, the incorporation substituents at the 2-position improved potency.
      Piperidines were found to be optimal, and further introduction of polar groups
      without compromising the activity was shown to be feasible. Careful positioning
      of the essential acidic moiety of the pharmacophore relative to the scaffold led
      to the discovery of vinyl tetrazoles with still greater potency.

PMID- 14698186
TI  - Enzymatic and hyperglycemia stability of chemically modified insulins with
      hydrophobic acyl groups.
AB  - The acylated insulins were synthesized by the reaction of insulin protected by p
      methoxybenzoxy carbonyl azide at Gly-A1 site with N-hydroxysuccinimide ester of
      caproic acid or benzoic acid (Cap-insulin and Bz-insulin). The noteworthy aspects
      are as follows: (a) the acylated insulins were more stable to the decomposition
      by various digestive enzymes as compared with native insulin in vitro. (b) Animal
      experiments using normal rats in vivo revealed that the Bz-insulin had an
      effective hypoglycemia activity almost similar to that of native insulin.

PMID- 14698187
TI  - Interaction assay of oligosaccharide with lectins using glycosylasparagine.
AB  - Glycosyl amino acids having natural glycan were useful for the interaction assay
      of oligosaccharides. A glycochip containing the whole structure of an
      oligosaccharide was easily prepared by the immobilization of the glycosyl amino
      acid. Furthermore, fluorescence probes were introduced into the glycosyl amino
      acid while maintaining the whole structure of oligosaccharide. By using these
      labeled oligosaccharides, fluorescence polarization (FP) and fluorescence
      correlation spectroscopy (FCS) analyzed the carbohydrate-lectin interaction in a
      solution assay system.

PMID- 14698188
TI  - Fentanyl derivatives bearing aliphatic alkaneguanidinium moieties: a new series
      of hybrid molecules with significant binding affinity for mu-opioid receptors and
      I2-imidazoline binding sites.
AB  - A new series of fentanyl derivatives [i.e., N-[1-(2-phenethyl)-4-piperidyl]-N
      (guanidinoalkyl)propanamide] bearing aliphatic alkaneguanidinium moieties were
      prepared. Their affinities for the micro opioid receptors and for the I(2)
      imidazoline binding sites (I(2)-IBS) were determined on human post-mortem
      prefrontal cortex membranes. All of these hybrid compounds had significant and/or
      very high affinity for both receptors in the nanomolar range, meaning an
      improvement compared to the prototype N-[1-(2-phenethyl)-4-piperidyl]-N
      (guanidinopropyl)propanamide previously reported.

PMID- 14698189
TI  - New bicyclam-GalCer analogue conjugates: synthesis and in vitro anti-HIV
      activity.
AB  - The synthesis of bipharmacophore anti-HIV compounds which, in a single molecule,
      combine two ligands, that is, the bicyclam AMD3100 and a GalCer analogue, that
      might inhibit several steps of the complex virus/cell cascade interactions has
      been performed. The 'double-drug' Gal-AMD3100 conjugates elicited inhibitory
      effects on T (or X4)-tropic HIV-1 replication in all CXCR4 expressing cell lines
      with EC(50) values ranging from 0.25 to 6.0 microM which were however
      approximately 40- to 125-fold lower than that of AMD3100. Concerning the
      mechanism of inhibition of the Gal-AMD3100 conjugates, experiments performed with
      X4 or R5HIV-1 strains and GHOST cells genetically modified to express CD4 and
      CXCR4 or CCR5 indicated clearly that the conjugates interact with CXCR4 and not
      with CCR5.

PMID- 14698190
TI  - Polar substitutions in the benzenesulfonamide ring of celecoxib afford a potent
      1,5-diarylpyrazole class of COX-2 inhibitors.
AB  - Several chemical modifications in the N(1)-benzenesulfonamide ring of celecoxib
      are presented. The series with a hydroxymethyl group adjacent to the sulfonamide
      was found to be the most potent modification that yielded many compounds
      selectively active against COX-2 enzyme in vitro.

PMID- 14698191
TI  - Effect of digestive site acidity and compatibility on the species, lipopily and
      bioavailability of iron, manganese and zinc in Prunus persica Batsch and
      Carthamus tinctorus.
AB  - The effects of compatibility, that is combination of Prunus persica Batsch (L.)
      and Carthamus tinctorus (L.), and different acidity of digestive site on the
      species, lipopily and bioavailability of coordinated complex of iron, manganese,
      and zinc in medical decoction were studied. In view of octanol, a long-chain
      alkanol, resembled as the configuration of carbohydrate and adipose in human
      body, the octanol- and water-solubility were used to define the species of trace
      element in phytomedicine, to identify the lipopily and bioavailability of trace
      element, and octanol-water system was adopted to study the distribution of trace
      element in decoction of P. persica Batsch (L.) (A), C. tinctorus (L.) (B), and
      combination of medicine A and B (C) in stomach and intestine. The total
      concentration, water- and octanol-solubility concentration of iron, manganese,
      and zinc in medicinal material A, B and C or its decoction under gastric and
      intestinal acidity, were determined respectively by flame atomic absorption
      spectrometry, analyzed and compared. The compatibility of medicine A and B
      enhances the extract percent, octanol-solubility concentration, and stability of
      coordinated complex of iron, manganese, and zinc. Different acidity of digestive
      site and compatibility of medicines impact on the ligands of iron, manganese, and
      zinc, then greatly affect the species and its quantification, the lipopily and
      bioavailability of trace element. Such influence is quite different for different
      trace element. Such factors, especially the concentration of octanol-solubility
      trace element, could be the basis of the dosage to avoid trace element overload.

PMID- 14698192
TI  - The design and synthesis of novel inhibitors of NADH:ubiquinone oxidoreductase.
AB  - Potent new inhibitors of NADH:ubiquinone oxidoreductase (complex I) have been
      designed, with the help of molecular modelling, by hybridisation of known complex
      I inhibitors with inhibitors of cytochrome c oxidoreductase. The most interesting
      compound was the chromone 7 which was a selective inhibitor of complex I (IC(50)
      15 nM) and showed acaricidal activity against spider mites.

PMID- 14698193
TI  - Modulation of selective serotonin reuptake inhibitor and 5-HT1A antagonist
      activity in 8-aza-bicyclo[3.2.1]octane derivatives of 2,3-dihydro-1,4
      benzodioxane.
AB  - 2,3-Dihydro-1,4-benzodioxanes with aryl 8-aza-bicyclo[3.2.1]oct-3-ene attachments
      2 produce compounds with potent 5-HT-T affinity, and weak 5-HT(1A) affinity and
      alpha(1) affinity. This compares with 2,3-dihydro-1,4-benzodioxanes containing 8
      aza-bicyclo[3.2.1] octan-3-ol attachments 4 which possess potent 5-HT(1A)
      affinity, moderate to good selectivity over alpha(1) and little 5-HT-T affinity.
      A 3-benzothiophene analogue of 4 (30) was synthesized which possesses potent 5
      HT(1A) affinity and especially good selectivity over both alpha(1) and 5-HT-T.

PMID- 14698194
TI  - Synthesis of novel 4'-substituted 16-membered ring macrolide antibiotics derived
      from leucomycins.
AB  - A series of novel 4'-substituted 16-membered ring macrolides was synthesized by
      the cleavage of the mycarose sugar and subsequent modification of 4'-hydroxyl
      group. This new class of macrolides antibiotics is acid stable. The synthetic
      methodology described here is expected to find application in the synthesis of
      new generation of macrolides that target the emerging bacterial resistance.

PMID- 14698195
TI  - 3-(4-Aminobutyn-1-yl)pyridines: binding at alpha 4 beta 2 nicotinic cholinergic
      receptors.
AB  - The binding of a series pyridylbutynylamines 6 was examined at alpha4beta2 nACh
      receptors. Structural modifications, comparing 6 with pyridyl ethers 2, did not
      consistently result in parallel effects on receptor affinity, suggesting possible
      differences in their modes of binding. Furthermore, the binding of amine 6a
      seemed to be accounted for by the newer vector pharmacophore models.

PMID- 14698196
TI  - Binding of an imidazopyridoindole at imidazoline I2 receptors.
AB  - 3,5,6,11-Tetrahydro-2H-imidazo[1',2':1,2]pyrido[3,4-b]indole (10) might be viewed
      as a fusion structure of two classes of I(2) imidazoline receptor ligands: 2-(2
      benzofuranyl)-2-imidazolines and beta-carbolines. Its high affinity (K(i)=7.3 nM)
      provides insight to how the two classes of agents might bind relative to one
      another at I(2) receptors.

PMID- 14698197
TI  - 7-Hydroxynaphthalen-1-yl-urea and -amide antagonists of human vanilloid receptor
      1.
AB  - A series of structurally simple 7-hydroxynaphthalenyl ureas and amides were
      discovered to be potent ligands of human vanilloid receptor 1 (VR1). 1-(7
      Hydroxynaphthalen-1-yl)-3-(4-trifluoromethylbenzyl)urea 5f exhibited nanomolar
      binding affinity (K(i)=1.0nM) and upon capsaicin challenge, behaved as a potent
      functional antagonist (IC(50)=4nM). The synthesis and structure-activity
      relationships (SARs) for the series are described.

PMID- 14698198
TI  - Affinity and intrinsic efficacy (IE) of 5'-carbamoyl adenosine analogues for the
      A1 adenosine receptor--efforts towards the discovery of a chronic ventricular
      rate control agent for the treatment of atrial fibrillation (AF).
AB  - The SAR for the affinity to the A(1) adenosine receptor and relative intrinsic
      efficacy (IE, [(35)S]-GTPgammaS binding) of a series of 5'-carbamate and 5'
      thionocarbamate derivatives of tecadenoson is described. Based on this SAR,
      selected compounds were evaluated in guinea pig isolated hearts to determine
      whether they were partial or full agonists with respect to their negative
      dromotropism, an A(1) AdoR mediated effect. Progress towards obtaining a partial
      A(1) AdoR agonist to potentially control ventricular rate during atrial
      fibrillation has been made with the discovery of several potent partial A(1) AdoR
      agonists (compounds 13, 14, and 17).

PMID- 14698199
TI  - Synthesis and biological activity of new quinoxaline antibiotics of echinomycin
      analogues.
AB  - Novel quinoxaline antibiotics having the methylenedithioether bridge as an
      analogue of echinomycin have been synthesized by insertion of methylene moiety
      between -S-S- bond. The compound 1a shows remarkable cytotoxicities against human
      tumor various cell lines, and is active VRE (vancomycin-resistant enterococci)
      within MIC range 0.5-8 microg/mL. According to the eukaryotic or prokaryotic
      data, 1a might be a first analogue to replace echinomycin.

PMID- 14698200
TI  - 2-(Aminomethyl)-benzamide-based glycine transporter type-2 inhibitors.
AB  - Structure-activity studies on benzamide 1 obtained from library screening led to
      the discovery of a novel series of potent and selective glycine transporter type
      2 inhibitors.

PMID- 14698201
TI  - New fatty acid oxidation inhibitors with increased potency lacking adverse
      metabolic and electrophysiological properties.
AB  - New inhibitors of palmitoylCoA oxidation were synthesized based on a structurally
      novel lead, CVT-3501 (1). Investigation of structure-activity relationships was
      conducted with respect to potency of inhibition of cardiac mitochondrial
      palmitoylCoA oxidation and metabolic stability. Potent and metabolically stable
      analogues 33, 42, and 43 were evaluated in vitro for cytochrome P450 inhibition
      and potentially adverse electrophysiological effects. Compound 33 was also found
      to have favorable pharmacokinetic properties in rat.

PMID- 14698202
TI  - Use of a modified yeast one-hybrid screen to identify BAF60a interactions with
      the Vitamin D receptor heterodimer.
AB  - A modified yeast one-hybrid screen was used to isolate proteins capable of
      interacting with the Vitamin D receptor (VDR) heterodimer complex while driving
      expression from a repressor Vitamin D response element (VDRE). Four of nine
      independent colonies recovered in the screen coded for full-length BAF60a, a
      component of the mammalian SWI/SNF complex. Deletion studies in yeast were unable
      to localize a unique region of BAF60a responsible for interaction with the
      heterodimer complex, as only the full-length protein would support reporter gene
      expression. Pull-down analyses revealed that BAF60a displayed strong interactions
      with either the unliganded or liganded heterodimer complex, but neither
      individual receptor component alone. Transient transfection analysis in opossum
      kidney (OK) cells indicated that BAF60a decreased basal transcriptional activity
      from the negative VDRE, but had no effect on hormone-induced repression.
      Transcriptional activity from an enhancer VDRE also exhibited decreased basal
      transcriptional activity, but also augmented hormone-dependent enhancer activity,
      resulting in an overall increased sensitivity to hormone. In summary, BAF60a has
      been identified as a factor that specifically interacts with the VDR heterodimer
      complex using a modified yeast one-hybrid selection strategy. This suggests that
      BAF60a may be a link between mammalian SWI/SNF-like chromatin remodeling
      complexes and the VDR heterodimer.

PMID- 14698203
TI  - Differential expression of Akt/protein kinase B, Bcl-2 and Bax proteins in human
      leiomyoma and myometrium.
AB  - The expression and activation of serine/threonine protein kinase, Akt, in
      leiomyoma and in adjacent myometrium of human uteri was studied parallel with the
      changes of Bcl-2, Bax proteins, estrogen and progesterone receptors during
      menstrual cycle and early stage of the menopause. Abundant expression of Akt
      protein was detected in the studied tissues during menstrual cycle, the rate of
      increase was higher in leiomyoma than in corresponding myometrium. The expression
      of estrogen receptor alpha, progesterone receptor and of Bcl-2 protein changed
      parallel with that of Akt protein. The level of phosphorylated Akt (pAkt(473))
      was seen only in leiomyoma samples from the growing period of tumors. At early
      stage of menopause levels of all studied proteins were lower than that in the
      menstrual cycle with the exception of Bax protein expression, which was high in
      leiomyoma. Our data suggest the involvement of phosphatidylinositol 3-kinase/Akt
      signaling in the pathomechanism of leiomyoma.

PMID- 14698204
TI  - Expression of P450 aromatase and 17beta-hydroxysteroid dehydrogenase type 1 at
      fetal-maternal interface during tubal pregnancy.
AB  - Steroidogenesis in the placenta has been studied widely, but little is known
      about steroid metabolism in ectopic pregnancy. Previous studies have indicated
      that trophoblast invasion and placentation in the uterus and the fallopian tube
      may be controlled by similar mechanisms. As far as 17beta-estradiol (E(2))
      production is concerned, it has been well demonstrated that its biosynthesis in
      the placenta involves the action of P450 aromatase (P450arom) and 17beta
      hydroxysteroid dehydrogenase type 1 (17HSD1). The purpose of this study was to
      characterize the expression pattern of P450arom and 17HSD1 at the fetal-maternal
      interface, particularly in various trophoblast cells, in tubal pregnancy. Using
      in situ hybridization, P450arom mRNA was localized in syncytiotrophoblast (ST)
      cells, which are mainly responsible for hormone production during pregnancy,
      whereas no signal was detected in villous cytotrophoblast (VCT), column CT and
      extravillous CT (EVCT) cells. Immunohistochemical assays revealed that 17HSD1 is
      present in ST cells, a large portion of EVCT cells and 20% of column CT cells. On
      the other hand, no expression of 17HSD1 was detected in VCT cells. In addition,
      17HSD1 was found in epithelial cells of the fallopian tube. Interestingly, the
      expression level of 17HSD1 in fallopian tube epithelium during tubal pregnancy
      was significantly higher than that during normal cycle. Our data provide the
      first evidence that normal and tubal pregnancies possess identical expression of
      P450arom and 17HSD1 in ST cells and therefore, similar E(2) production in the
      placenta. Further, the association of 17HSD1 with EVCT cells indicates that
      17HSD1 perhaps play a role in trophoblast invasion. Finally, increased expression
      of 17HSD1 in epithelial cells of fallopian tube may lead to a local E(2) supply
      sufficient for the maintenance of tubal pregnancy.

PMID- 14698205
TI  - In vitro farnesoid X receptor ligand sensor assay using surface plasmon resonance
      and based on ligand-induced coactivator association.
AB  - Ligand binding to nuclear receptors leads to a conformational change that
      increases the affinity of the receptors to coactivator proteins. We have
      developed a ligand sensor assay for farnesoid X receptor (FXR) in which the
      receptor-coactivator interaction can be directly monitored using surface plasmon
      resonance biosensor technology. A 25-mer peptide from coactivator SRC1 containing
      the LXXLL nuclear receptor interaction motif was immobilized on the surface of a
      BIAcore sensor chip. Injection of the FXR ligand binding domain (FXRLBD) with or
      without the most potent natural ligand, chenodeoxycholic acid (CDCA), over the
      surface of the chip resulted in a ligand- and LXXLL motif-dependent interaction.
      Kinetic analysis revealed that CDCA and its conjugates decreased the equilibrium
      dissociation constant (K(d)) by 8-11-fold, indicating an increased affinity.
      Using this technique, we found that a synthetic bile acid sulfonate,
      3alpha,7alpha-dihydroxy-5beta-cholane-24-sulfonate, which was inactive in a FXR
      response element-driven luciferase assay using CV-1 cells, caused the most potent
      interaction, comparable to the reaction produced by CDCA. This method provides a
      rapid and reliable in vitro ligand assay for FXR. This kinetic analysis-featured
      technique may be applicable to mechanistic studies.

PMID- 14698206
TI  - Photoaffinity labeling identification of thyroid hormone-regulated glucocorticoid
      binding peptides in rat liver endoplasmic reticulum: an oligomeric protein with
      high affinity for 16beta-hydroxylated stanozolol.
AB  - Steroid-binding proteins unrelated to the classical nuclear receptors have been
      proposed to play a role in non-genomic actions of the17alpha-alkylated
      testosterone derivative (17alpha-AA) stanozolol (ST). We have previously reported
      that male rat liver endoplasmic reticulum contains two steroid-binding sites
      associated with high molecular mass oligomeric proteins: (1) the ST-binding
      protein (STBP); and (2) the low-affinity glucocorticoid-binding protein (LAGS).
      To further explore the role of LAGS on the mechanism of action of ST, we have now
      studied: (1) the interaction of ST and its hydroxylated metabolites with
      solubilized LAGS and the cytosolic glucocorticoid receptor (GR); and (2) the
      effects of hormones on the capability of STBP to bind ST. We found that, unlike
      17alpha-methyltestosterone, neither ST nor its hydroxylated metabolites bind to
      GR. However, the 16beta-hydroxylation of ST significantly increases the
      capability of LAGS to bind ST. Interestingly, 3'-hydroxylation of ST abrogates
      the capability of LAGS to bind ST. ST (k(i)=30 nM) and 16beta-hydroxystanozolol
      (k(i)=13 nM) bind with high affinity to LAGS, and are capable of accelerating the
      rate of dissociation of previously bound dexamethasone from the LAGS. STBP and
      LAGS are strongly induced by ethinylestradiol. However, unlike STBP, LAGS is
      regulated by thyroid hormones and growth hormone, which proves that these steroid
      binding activities are associated with different binding sites. These findings
      seem to suggest a novel mechanism for ST whereby membrane-associated
      glucocorticoid-binding activity is targeted by the 16beta-hydroxylated metabolite
      of ST. ST and its 16beta-hydroxylated metabolite modulate glucocorticoid activity
      in the liver through negative allosteric modulation of LAGS, with the result of
      this interaction an effective increase in classical GR-signaling by increasing
      glucocorticoid availability to the cytosolic GR.

PMID- 14698207
TI  - Effects of leptin and leptin fragments on steroid secretion of freshly dispersed
      rat adrenocortical cells.
AB  - The biological actions of leptin on target tissues are mediated via several
      isoforms of receptors (Ob-Rs), which may differently interact with native leptin
      and its fragments. Based on the presence in the rat adrenals of at least two Ob-R
      isoforms and the conflicting findings on the effect of leptin on adrenocortical
      secretion, we investigated the effects of the native leptin and several leptin
      fragments (10(-8) and 10(-6)M) on aldosterone and corticosterone secretion from
      freshly dispersed rat zona glomerulosa (ZG) and zona fasciculata-reticularis
      (ZF/R) cells. Reverse transcription (RT)-polymerase chain reaction (PCR) showed
      the expression of Ob-Ra and Ob-Rb mRNAs in both ZG and ZF/R cells. Native murine
      leptin (1-147) enhanced aldosterone and corticosterone secretion from dispersed
      ZG and ZF/R cells, and similar effects were elicited by murine leptin fragment
      116-130, and human leptin fragments 138-167, 150-167 and [Tyr] 26-39. Human
      leptin fragment 93-105 was ineffective, while fragment 22-56 decreased
      corticosterone output without affecting aldosterone secretion. Taken together,
      our findings indicate that in rat adrenocortical cells leptin and leptin
      fragments may differently interact with Ob-Rs or interact with different Ob-R
      isoforms. Moreover, they suggest that (1) the direct adrenocortical secretagogue
      effect of leptin mainly depends on the C-terminal sequence 116-166; and (2) the N
      terminal sequence is not needed for leptin to activate Ob-Rs positively coupled
      to steroidogenesis, but is possibly responsible for a direct inhibitory effect on
      glucocorticoid secretion.

PMID- 14698208
TI  - Effects of prolonged stanozolol treatment on antioxidant enzyme activities,
      oxidative stress markers, and heat shock protein HSP72 levels in rat liver.
AB  - The abuse of anabolic-androgenic steroids (AAS) to enhance physical performance
      is widespread in sport communities despite their reported side effects. Since the
      biochemical bases for the hepatotoxic effects of these compounds are largely
      unknown, this investigation was aimed at testing whether prolonged (8 weeks)
      treatment with high doses (2 mg kg(-1) body weight; 5 d wk(-1)) of stanozolol
      (ST), either alone or in conjunction with treadmill-exercise training, induced
      changes in oxidative stress biomarker levels and antioxidant defence systems in
      rat liver. After ST oral administration, the mean values of serum parameters
      related to hepatic function were within normal ranges. No changes in protein
      carbonyl content and in the reduced to oxidized glutathione (GSH/GSSG) ratio were
      detected in liver homogenates of ST-treated rats, whereas thiobarbituric acid
      reactive substances (TBARS) levels resulted increased (P<0.05). Total superoxide
      dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities were
      higher (P<0.05) in the liver of treated rats but mitochondrial SOD and
      glutathione reductase (GR) activities, and the 72 kDa heat shock protein (HSP72)
      level were not modified. Chronic exercise alone did not change any of the above
      parameters except for a remarkable enhancement of HSP72 expression; in no case
      training modified the effects of ST treatment. The present data show that 8 wk
      ingestion of ST, either with or without concurrent exercise training, can induce
      oxidative stress in rat liver despite the up-regulation of enzymatic antioxidant
      activities.

PMID- 14698209
TI  - Dehydroepiandrosterone as an inducer of mitochondrial permeability transition.
AB  - This paper reports an investigation upon the effect of dehydroepiandrosterone
      (DHEA) on some mitochondrial membrane functions, such as electron transport,
      transmembrane electric gradient and calcium permeability. It was found that the
      hormone induced the efflux of accumulated matrix Ca(2+), inhibited Site I of the
      respiratory chain, as well as bringing about the collapse of the transmembrane
      potential, and mitochondrial swelling. Taking into account that cyclosporin A
      (CSA) inhibited Ca(2+) release and the collapse of the transmembrane potential,
      it is concluded that the hormone may induce the opening of a non-specific
      transmembrane pore. The mechanism of pore opening is ascribed to peroxidation of
      the membrane lipid bilayer. It should be mentioned that estrone, even at the
      concentration of 200 microM, failed to reproduce the behavior of
      dehydroepiandrosterone on mitochondrial functions.

PMID- 14698210
TI  - Metabolism of the soy isoflavones daidzein, genistein and glycitein in human
      subjects. Identification of new metabolites having an intact isoflavonoid
      skeleton.
AB  - Epidemiological studies have associated high soy intake with a lowered risk for
      certain hormone-dependent diseases. Soy and soy foods are rich sources of
      isoflavones, which have been shown to possess several biological activities. In
      this study, the metabolism of soy isoflavones daidzein, genistein and glycitein
      was investigated in human subjects. The aim was to find and identify urinary
      phase I metabolites of isoflavones, which have an intact isoflavonoid skeleton,
      and which might possess some bioactivity. Six volunteers included three soy bars
      per day into their normal western diet for a 2-week period. Daily urine samples
      were collected before, and after the supplementation period. Urine samples were
      hydrolyzed with Helix pomatia, extracted with diethyl ether, purified with
      Sephadex LH-20 chromatography, and analyzed as trimethylsilyl derivatives using
      gas chromatography-mass spectrometry (GC-MS). The structures of the isoflavone
      metabolites were identified using authentic reference compounds. The metabolites,
      for which authentic reference compounds were not available, were identified by
      the interpretation of mass spectra. Several new isoflavone metabolites were
      identified, and the presence of previously reported metabolites confirmed. The
      metabolic pathways of daidzein, genistein and glycitein are presented on the
      basis of the identification of the metabolites in human urine after soy
      supplementation.

PMID- 14698211
TI  - Flexibility of the endogenous progesterone lactonisation pathway in Aspergillus
      tamarii KITA: transformation of a series of cortical steroid analogues.
AB  - A range of cortical steroids have been transformed by the fungus Aspergillus
      tamarii, which has the ability to convert progesterone to testololactone in high
      yield through a four step enzymatic pathway. 16alpha,17alpha-Epoxyprogesterone
      underwent a rare epoxide opening resulting in a unique inversion of
      stereochemistry to give 16beta-hydroxy-17alpha-oxa-D-homo-androst-4-en-3,17
      dione. The metabolism of deoxycorticosterone resulted in relatively efficient
      transformation to testololactone with no other products isolated. Transformation
      of 17alpha-hydroxyprogesterone yielded 17alpha-oxa-D-homo-androst-1,4-dien-3,17
      dione, a lactone not previously isolated from A. tamarii. Cortexolone was
      transformed to the 20(R)-alcohol with no further transformation observed.
      Evidence is also presented for the presence of a highly flexible but
      stereospecific keto-reductase. All metabolites were isolated by column
      chromatography and were identified by 1H, 13C NMR, DEPT analysis and other
      spectroscopic data.

PMID- 14698213
TI  - 21-Acetoxy-pregna-4(5),9(11),16(17)-triene-21-ol-3,20-dione conversion by
      Nocardioides simplex VKM Ac-2033D.
AB  - The conversion of 21-acetoxy-pregna-4(5),9(11),16(17)-triene-21-ol-3,20-dione (I)
      by Nocardioides simplex VKM Ac-2033D was studied purposed selective production of
      its 1(2)-dehydroanalogues-value precursors in the synthesis of modern
      glucocorticoids starting from 9alpha-hydroxyandrostenes. 21-Acetoxy-pregna
      1(2),4(5),9(11),16(17)-tetraene-21-ol-3,20-dione (II), pregna-4(5),9(11),16(17)
      triene-21-ol-3,20-dione (III) and pregna-1(2),4(5),9(11),16(17)-tetraene-21-ol
      3,20-dione (IV) were revealed as metabolites, and the structures were confirmed
      by mass spectrometry and (1)H nuclear magnetic resonance (NMR) spectroscopy. The
      metabolic pathways of I by N. simplex included 1(2)-dehydrogenation and
      deacetylation. The sequence of the reactions was shown to depend on the
      transformation conditions. The presence of both soluble and membrane associated
      steroid esterases in N. simplex was demonstrated using cell fractionation. Unlike
      inducible 1(2)-dehydrogenase, steroid esterase was shown to be constitutive. The
      conditions providing selective accumulation of II from I by whole N. simplex
      cells were determined.

PMID- 14698212
TI  - Tetrahydrocortisol-apolipoprotein A-I complex specifically interacts with
      eukaryotic DNA and GCC elements of genes.
AB  - Tetrahydrocortisol stimulates DNA and protein biosynthesis in hepatocytes only
      when it enters the complex with apolipoprotein A-I. Tetrahydrocortisol
      apolipoprotein A-I (THC-apoA-I) complex specifically interacts with eukaryotic
      DNA isolated from rat liver. In the process of interaction, rupture of hydrogen
      bonds between the pairs of nitrous bases occurs with the formation of single
      stranded DNA structures. In such state DNA forms complexes with DNA-dependent RNA
      polymerase. The most probable site of binding the tetrahydrocortisol
      apolipoprotein A-I complex with DNA is the sequence of CC(GCC)(n) type entering
      the structure of many genes, among them the structure of human apolipoprotein A-I
      gene. Oligonucleotide of this type has been synthesized. Association constant
      (K(ass)) of it with tetrahydrocortisol-apolipoprotein A-I complex was shown to be
      1.66 x 10(6)M(-1). Substitution of tetrahydrocortisol for cortisol in the complex
      results in a considerable decrease of K(ass). It was assumed that in the GC-pairs
      of the given sequence tetrahydrocortisol itself participates in the formation of
      hydrogen bonds with cytosine, favoring their rupture with complementary base
      guanine.

PMID- 14698214
TI  - Production of malodorous steroids from androsta-5,16-dienes and androsta-4,16
      dienes by Corynebacteria and other human axillary bacteria.
AB  - The biotransformations of a number of steroids, chiefly 5,6,16,17-tetradehydro
      androstanes, are reported. The strains investigated were Corynebacteria sp. G38,
      G40, G41, B, Brevis sp. CW5 and Micrococcus sp. M-DH2. Corynebacterium sp. G41
      proved remarkably efficient in effecting oxidative isomerisation of 5-ene-3
      sterols into the corresponding 4-en-3-ones. The main biochemical reactions
      involved were oxidation at C-3; no reduction processes were observed. Conversions
      of 3beta-sterols into the C-3 oxo-steroids were high, but were correspondingly
      low for the 3alpha-sterol epimers. Androsta-4,16-dien-3-one and 5beta-androsta-16
      en-3-one are crucial to the formation of malodour. The rate of formation of these
      compounds was measured over 72 h incubation periods using three substrates:
      androsta-5,16-dien-3beta-ol, androsta-4,16-dien-3beta-ol and androsta-5,16-dien-3
      one. Induction studies of the transformation of the androsta-5,16-dien-3beta-ol
      into the very odorous compound androsta-4,16-dien-3-one showed that cells
      incubated with a mixture of antibiotics displayed the same extent of
      biotransformation as normal cells if the concentration of antibiotic was low (1,
      3, 5 and 7 microg/ml), although at concentrations higher than 10 microg/ml,
      biotransformation yields were reduced. Pre-incubation with a 3beta-fluoro-steroid
      inhibited the formation of the odorous androsta-4,16-dien-3-one.

PMID- 14698215
TI  - Molecular cloning and characterization of tiger shrimp (Penaeus monodon)
      transglutaminase.
AB  - Transglutaminases (TG) are important for blood coagulation and post-translation
      remodeling of proteins. Using a plaque screening assay, we isolated cDNA encoding
      a novel TG from a shrimp (Penaeus monodon) hemocyte cDNA library. The TG cDNA
      consists of 2988 bp with an open reading frame of 2271 bp. The deduced protein
      has 757 amino acid residues, a calculated molecular mass of 84,713 Da and an
      isoelectric point of 5.56. Neither a typical hydrophobic leader sequence nor a
      transmembrane domain could be identified from the deduced sequence. Thus, shrimp
      TG may be a typical cytoplasmic protein. The sequence of shrimp TG was similar to
      crayfish, other invertebrate and vertebrate TG sequences. Enzyme activity was
      detected in all organs tested. This is consistent with the widespread, low-level
      expression of TG mRNA. However, high levels of TG expression were detected in
      hematopoietic tissue. TG signals were stronger in mitotic cells, indicating that
      cell proliferation and TG synthesis are associated. Preliminary data showed that
      recombinant TG existed the enzyme activity but lacked coagulation activity.

PMID- 14698216
TI  - Cloning and characterization of an Mx gene and its corresponding promoter from
      the zebrafish, Danio rerio.
AB  - Type I interferons (IFNs) represent a crucial component of the innate immune
      response to viruses. An important downstream effector of IFN is the Mx gene,
      which is activated solely through this pathway. Mx proteins are characterized by
      a tripartite GTP-binding domain, dynamin family signature, and leucine zipper
      motif. Mx genes are transcribed upon activation of an interferon-stimulated
      response element (ISRE) located in the Mx promoter region. In this article, we
      describe the cloning and analysis of an Mx gene and its corresponding promoter
      from the zebrafish (Danio rerio). The deduced amino acid sequence of zebrafish Mx
      contains the conserved GTP-binding domain, dynamin family signature, and leucine
      zipper motif common to Mx proteins, and shows a 50% identity to human MxA and 69%
      identity both to rainbow trout and to Atlantic salmon. Zebrafish liver cells
      produced high levels of Mx mRNA in response to induction by the known IFN-inducer
      polyinosinic-polycytidylic acid (Poly[I:C]). The zebrafish Mx promoter contains
      two ISREs homologous to those found in the promoter regions of many IFN-inducible
      genes, and was able to drive transcription of a luciferase reporter gene when
      induced by either purified zebrafish IFN or Poly[I:C].

PMID- 14698217
TI  - Cloning and analyses of a BPI/LBP cDNA of the Atlantic cod (Gadus morhua L.).
AB  - Using the differential screening technique, a cDNA related to the mammalian
      family of lipid transfer/lipopolysaccharide-binding proteins was cloned from the
      Atlantic cod (Gadus morhua L.). The gene is an ortholog of a recently identified
      gene of rainbow trout (Oncorhynchus mykiss). Phylogenetic analyses suggest that
      teleost BPI/LBP are modern descendants of the ancestor of mammalian
      bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding
      protein (LBP), and a gene of the urochordate Ciona intestinalis is related to
      this gene family. Molecular modeling suggests that the structure of cod BPI/LBP
      is similar to mammalian BPI and LBP, while its highly basic character is similar
      to BPI. Cod BPI/LBP is constitutively expressed in head-kidney (HK) leukocytes.
      After intraperitoneal injection of bacterin high levels of cod BPI/LBP mRNA were
      detected also in peripheral blood cells and spleen, while moderate to low levels
      of transcript were found in heart, liver, gills, skin, brain, and intestine. We
      conclude that the patterns of charge and expression of cod BPI/LBP are more
      similar to mammalian BPI than to mammalian LBP.

PMID- 14698218
TI  - Characteristics and primary structure of a galectin in the skin mucus of the
      Japanese eel, Anguilla japonica.
AB  - The characteristics and primary structure of AJL-1, one of the lectins in the
      skin mucus of the Japanese eel (Anguilla japonica), were examined. This lectin
      exhibited beta-galactoside specific activity in a Ca2+ independent manner. We
      previously reported that its molecular mass was 16,091Da, although it was
      approximately 30 kDa as determined by gel filtration, indicating that it is a
      homodimer having non-covalent bonds. This lectin was composed of 142 amino acid
      residues having no half-cystinyl residues, and showed homology to members of the
      galectin family, especially to proto-type galectins. Gene expression of this
      lectin was detected in skin only, and relative expression was high in an
      individual that exhibited resistance to infectious disease. AJL-1 showed
      agglutinating activity against pathogenic bacteria, Streptococcus difficile. This
      suggests that AJL-1 functions as an important defensive factor at the body
      surface.

PMID- 14698219
TI  - Immunohistochemical assessment of the neurosecretory cells of the chicken thymus
      using a novel monoclonal antibody against avian chromogranin A.
AB  - An immunocytochemical approach to the identification of neuroendocrine cells in
      the thymus of the chicken was taken based on a novel monoclonal antibody against
      turkey chromogranin A (CgA), a classic marker protein for neuroendocrine cells.
      CgA-immunoreactive cells were readily observed in the thymus, and were typically
      confined to the medullary side of the corticomedullary junction of the thymic
      lobules. Reversed transcription PCR confirmed local production of CgA in the
      thymus. The majority of CgA+ cells were small and round or oval in shape but some
      cells were larger and had conspicuous extensions. Immunofluorescent double
      staining experiments with antibodies against Neuron-specific enolase and with a
      neural crest marker (HNK-1) indicated no demonstrable overlap between the CgA
      positive cells and either of the above cell populations, demonstrating the
      existence of three distinct neuronal/neuroendocrine cell populations in the avian
      thymus.

PMID- 14698220
TI  - A developmental investigation of the liver, bone marrow and spleen of the stripe
      faced dunnart (Sminthopsis macroura).
AB  - The development of the liver, bone marrow and spleen have been investigated in
      the stripe-faced dunnart. At birth, the liver was undergoing haematopoiesis but
      the level declined rapidly and by day 50 after birth the liver was histologically
      mature. Both the bone marrow and spleen were non-haematopoietic at birth but
      initiated haematopoiesis shortly thereafter. Bone marrow was initially detected
      at day 11 postpartum. By 57 days after birth, adipocytes had infiltrated the
      marrow and were abundant by day 60 after birth. Mitotic cells were observed in
      remaining areas of marrow until at least 170 days postpartum. The spleen at birth
      was undifferentiated, with trabeculae appearing by day 42. Red and white pulp
      areas became apparent by day 43 and were well defined by day 57 after birth. In
      summary, the pattern of the development of the liver, bone marrow and spleen in
      the stripe-faced dunnart were similar to that observed in eutherians and other
      metatherians studied to date.

PMID- 14698221
TI  - Histological studies on the ontogeny of bovine gut-associated lymphoid tissue:
      appearance of T cells and development of IgG+ and IgA+ cells in lymphoid
      follicles.
AB  - The development and distribution of lymphocyte subsets in bovine gut-associated
      lymphoid tissues (ileal and jejunal Peyer's patches (PP)) were examined. Before
      birth, the composition of lymphocyte subsets in both PP follicles did not differ
      except for the dimensions of the interfollicular area and the dome region. Many
      IgM+ cells were observed in these follicles, but very few CD3+, IgG+, and IgA+
      cells could be found. At neonatal period, the IgG+ cells, which did not produce
      IgG mRNA, were dominant within both PP follicles. From 1 month after birth, many
      CD3+ cells, IgG mRNA expression, and IgA mRNA expression were detected within the
      jejunal PP follicles, but very few were in the ileal PP follicles. These data
      suggest that the characteristics of the jejunal PP follicles metamorphose into
      secondary lymphoid tissue such as germinal centers at around 1 month after birth,
      whereas the characteristics of ileal PP follicles were distinct from those of
      germinal centers.

PMID- 14698223
TI  - Innate immunity: an overview.
AB  - Though sometimes portrayed as "new," the science of innate immunity made its
      start more than 100 years ago. Recent progress has reflected the application of
      new methods to old problems. In particular, genetic dissection of innate immune
      pathways has been pursued with great success in model organisms. This has opened
      the way to an understanding of innate immune sensing. The effector arm of innate
      immunity has also been tackled, largely though the use of biochemical methods.

PMID- 14698224
TI  - TIR domain-containing adaptors define the specificity of TLR signaling.
AB  - The concept that Toll-like receptors (TLRs) recognize specific molecular patterns
      in various pathogens has been established. In signal transduction via TLRs,
      MyD88, which harbors a Toll/IL-1 receptor (TIR)-domain and a death domain, has
      been shown to link between TLRs and MyD88-dependent downstream events leading to
      proinflammatory cytokine production and splenocyte proliferation. However, recent
      studies using MyD88-deficient mice have revealed that some TLRs possess a MyD88
      independent pathway, which is represented by interferon (IFN)-beta production
      induced by LPS stimulation. This indicates that additional signaling molecules
      other than MyD88 exist in the TLR signaling pathway. Indeed, two additional TIR
      domain-containing adaptors, TIRAP/Mal and TRIF, have recently been identified.
      Both define the specific biological responses of each TLR.

PMID- 14698225
TI  - Dectin-1 and its role in the recognition of beta-glucans by macrophages.
AB  - beta-Glucans are well known leukocyte activators that have shown protective
      benefits in a variety of animal disease models, yet the mechanism of action of
      these carbohydrates remains unknown. We have shown that Dectin-1, a murine type
      II C-type lectin-like receptor, was able to non-opsonically recognize beta-1,3
      and beta-1,6 linked glucan rich particles and intact yeast. Dectin-1 is widely
      expressed in murine tissues, particularly on the monocyte/macrophage and
      neutrophil lineages, on dendritic cells (DC) and at a lower level on a sub
      population of T cells. The human homologue of Dectin-1 was identified and is
      functionally similar to the murine molecule. Human Dectin-1 differs from the
      murine molecule in that it is expressed as two major splice variants that are
      selectively expressed in particular leukocyte populations. In addition to beta
      glucans, Dectin-1 also recognizes an endogenous ligand on T cells. The ligand and
      the immunological role of Dectin-1 mediated T cell interactions remain to be
      described.

PMID- 14698226
TI  - Peptidoglycan recognition proteins (PGRPs).
AB  - Innate immune system recognizes microorganisms through a series of pattern
      recognition receptors that are highly conserved in evolution. Peptidoglycan
      recognition proteins (PGRPs) are pattern recognition molecules that are conserved
      from insects to mammals and recognize bacteria and their unique cell wall
      component, peptidoglycan (PGN). Drosophila, mosquito, and mammals have families
      of 13, 7, and 4 PGRP genes, respectively, and some of these genes are
      alternatively spliced. PGRPs are differentially expressed in various cells and
      tissues, their expression is often upregulated by bacteria, and they mediate host
      responses to bacterial infections. Insect PGRPs have four known effector
      functions that are unique for insects: activation of prophenoloxidase cascade,
      activation of Toll receptor, activation of Imd pathway, and induction of
      phagocytosis. One function, amidase activity, is shared by some insect and
      mammalian PGRPs, whereas antibacterial activity of some mammalian PGRPs is unique
      for mammals.

PMID- 14698227
TI  - Antimicrobial defences in Drosophila: the story so far.
AB  - Drosophila has recently emerged as an important model for the study of innate
      immunity. Two signalling pathways triggered by different classes of
      microorganisms control its antimicrobial defence. This phenomenon has been
      recently shown to reflect specificity in pathogen recognition and in subsequent
      induction of the systemic immune response. In the following we will review recent
      developments in the field, which give a more defined picture of how the
      Drosophila innate immune system works both in terms of microbe perception and
      effector molecules, as well as point to the missing pieces of the puzzle.

PMID- 14698228
TI  - Evolution of the complement system.
AB  - The human complement system is composed of more than 30 serum and cell surface
      components, and most of these components show a characteristic domain structure,
      enabling us to trace the evolution of the genes based on their structures.
      Ongoing genome projects in both vertebrates and invertebrates revealed that most
      domains used by mammalian complement components are found in both protostomes and
      deuterostomes. However, the unique combinations of them as found in mammalian
      complement components are present only in deuterostomes, indicating that the
      complement system was established in the deuterostome lineage. Unexpectedly, the
      complement system of an invertebrate deuterostome, ascidian, shows a similar
      level of complexity as that of mammals. However, phylogenetic analysis suggested
      that expansion of complement genes by gene duplications occurred independently
      both in the ascidian and vertebrate lineages. Although most characteristic domain
      structures of the mammalian complement components are found in ascidians,
      detailed evolutionary analysis casts doubt on their mutual reactivity. Thus, the
      vertebrate complement system seems to be established by integrating some
      independent parts into one reaction system.

PMID- 14698229
TI  - Thioester-containing proteins and insect immunity.
AB  - Here, we discuss the role of thioester-containing proteins in innate immune
      responses of insects. TEPs are represented by multi-member families both in the
      fruitfly, Drosophila melanogaster, and in the mosquito, Anopheles gambiae.
      Phylogenetic analysis of the family suggests that in these two dipteran species
      evolution of TEPs followed independent scenarios as a result of specific
      adaptation to distinct ecological environments. Research on these two relatively
      simple model systems, which lack adaptive immunity, may provide new insights into
      the evolutionary origins and functions of this important protein family.

PMID- 14698231
TI  - Separation and analysis of colloidal/nano-particles including microorganisms by
      capillary electrophoresis: a fundamental review.
AB  - A review is presented on the CE analysis of colloidal/nano particles. Topics
      discussed include the CE separation of polymeric, inorganic, microbial (i.e.
      viruses, bacteria, fungi, and whole cells), and sub-cellular particles (i.e.
      mitochondria and nuclei). Several of the encountered difficulties in analysis are
      presented as well as the methods employed to overcome them.

PMID- 14698233
TI  - Micro-thermal focusing field-flow fractionation.
AB  - Focusing mechanism was effectively exploited to separate large (micrometer-size)
      particles by using new micro-thermal field-flow fractionation (micro-TFFF). It
      has been shown that the retention order of micrometer-size particles at high
      field strength can be explained by the mechanism of steric exclusion only at
      lowest flow rates of the carrier liquid. A simplistic, purely mechanical model of
      steric exclusion is not accurate to describe the retention at higher flow rates
      where the focusing phenomenon appears. Despite the fact that the thickness of the
      channel for micro-FFF cannot be reduced without taking into account a possible
      deterioration of the separation due to the contribution of "steric exclusion"
      mechanism, this paper demonstrates, in agreement with our previous results, that
      if the operational conditions were conveniently chosen, namely a low flow rate, a
      reasonable fit of the experimental retention data with the theory of steric
      exclusion mechanism in FFF was found and the separation of micron-size particles
      can be accomplished. However, high selectivity and resolution and high-speed
      separation were achieved if the focusing effect has clearly dominated the FFF
      mechanism. As a result, it seems that the micro-TFFF is the most universal
      technique which can be applied for the separation of the synthetic and natural
      macromolecules within an extended range of molar masses up to ultra-high molar
      masses and for the particles of various chemical nature and origin in a nano-size
      range as well as for large (micrometers) particles. Until nowadays, only
      sedimentation and flow field-flow fractionation techniques in so called "steric"
      modes were applied for the separations of large size particles. This application
      of micro-TFFF in focusing mode for the separation of large size particles is the
      first one described in the literature.

PMID- 14698232
TI  - Magnetic hydrophilic methacrylate-based polymer microspheres designed for
      polymerase chain reactions applications.
AB  - Magnetic hydrophilic non-porous P(HEMA-co-EDMA), P(HEMA-co-GMA) and PGMA
      microspheres were prepared by dispersion (co)polymerization of 2-hydroxyethyl
      methacrylate (HEMA) and ethylene dimethacrylate (EDMA) or glycidyl methacrylate
      (GMA) in the presence of several kinds of magnetite. It was found that some
      components used in the preparation of magnetic carriers interfered with
      polymerase chain reaction (PCR). Influence of non-magnetic and magnetic
      microspheres, including magnetite nanoparticles and various components used in
      their synthesis, on the PCR course was thus investigated. DNA isolated from
      bacterial cells of Bifidobacterium longum was used in PCR evaluation of non
      interfering magnetic microspheres. The method enabled verification of the
      incorporation of magnetite nanoparticles in the particular methacrylate-based
      polymer microspheres and evaluation of suitability of their application in PCR.
      Preferably, electrostatically stabilized colloidal magnetite (ferrofluid) should
      be used in the design of new magnetic methacrylate-based microspheres by
      dispersion polymerization.

PMID- 14698234
TI  - Neurophysiologic detector-a selective and sensitive tool in high-performance
      liquid chromatography.
AB  - In the present study neurons from the olfactory system of the fish crucian carp,
      Carassius carassius L. were used as components in an in-line neurophysiologic
      detector (NPD) to measure physiological activities following the separation of
      substances by high-performance liquid chromatography (HPLC). The skin of crucian
      carp, C. carassius L. contains pheromones that induce an alarm reaction in
      conspecifics. Extra-cellular recordings were made from neurons situated in the
      posterior part of the medial region of the olfactory bulb known to mediate this
      alarm reaction. The nervous activity of these specific neurons in the olfactory
      bulb of crucian carp was used as an in-line neurophysiologic detector. HPLC was
      performed with an HP 1100 model equipped with a diode array detector (DAD) and
      ChemStation software. An adsorbosphere nucleotide-nucleoside 7 microm column was
      used to separate the substances in the skin extract using artificial pound water
      (APW) as the mobile phase. UV spectral detection was performed at 214, 254 and
      345 nm, and scans (190-400 nm) were collected continuously. This system enabled
      the selection of peaks in the chromatogram with fish alarm pheromone activity.
      The neurons in parts of the olfactory system from different aquatic organisms and
      vertebrates can be used for the detection of species-specific stimuli such as
      sexual and alarm signals, food odours, and other physiologically significant
      substances. NPDs clearly offer new and promising options for in-line HPLC as
      highly selective and sensitive detectors in biological, medical and
      pharmaceutical research.

PMID- 14698235
TI  - Bionanocompositional chitosan-silica sorbent for liquid chromatography.
AB  - Preparation of hybrid nanocompositional chitosan/silica sorbent was carried out.
      It was shown that formation of gel in sol-gel process of hydrolytic
      polycondensation of tetraethoxysilane (TEOS) with including of chitosan consists
      of two stages. Suppression of crystallization of chitosan in obtained two-phase
      system and changes in IR spectra are evidenced of interactions between molecules
      of chitosan and silanol groups of silica network. The resulting hybrid
      chitosan/silica sorbent was tested by high-performance liquid chromatography
      (HPLC).

PMID- 14698236
TI  - Field gas chromatography-mass spectrometry for fast analysis.
AB  - The objective of this presentation is to demonstrate the original device and
      procedure for fast gas chromatography-mass spectrometry (GC-MS) analysis of
      gaseous and liquid samples and to discuss its features and capabilities. The
      concept was developed in order to expand the range of compounds suitable for GC
      separation and to reduce the time of analysis. Field GC-MS, consisting of
      original "concentrator-thermodesorber" (CTD) unit, multiple module GC system and
      compact magnetic mass spectrometer with powerful two-stage vacuum system and
      multicollector ion detector, is represented. The whole weight of the device is 90
      kg. Power consumption is 250 W. The device and analytical procedures allow high
      speed screening of toxic substances in air and extracts within 100 s per sample.
      The examples of applications are described, including fast screening of tributyl
      phosphate (TBP) in air at low ppt level at the rate 1 sample/min.

PMID- 14698237
TI  - Miniaturized mass-selective detector with atmospheric pressure chemical
      ionization.
AB  - The miniaturized mass-spectrometric detector with atmospheric pressure chemical
      ionization (APCI) is described. The analyzer employed in this instrument is the
      monopole with rod 54 mm in length and 2 mm in radius, which retains its
      efficiency up to 0.13 Pa ( approximately 10(-3)Torr). Together with the ion
      source, channeltron ion detector, radio frequency power supply and preamplifier,
      it is packed into a case with dimension of 185 mm x 100 mm x 70 mm. Mass
      spectrometer with the whole vacuum system weighs about 20 kg. In spite of low
      power of the vacuum system, the limit of detection at ppt level is achieved. The
      "strong" fragmentation mode is suggested for high-specific detection of phosphor
      containing substances. The detector conforms to multicapillary column attachment.

PMID- 14698238
TI  - Evaluation of liquid chromatography column retentivity using macromolecular
      probes. IV. Poly(ethylene glycol) bonded phase.
AB  - Interaction properties of the novel HPLC silica gel-poly(ethylene glycol) (PEG)
      bonded phase were evaluated applying polymeric test substances, viz.
      polystyrenes, poly(methyl methacrylate)s, poly(ethylene oxide)s and poly(2-vinyl
      pyridine)s, and eluents of different polarities. Silanols on the silica gel
      surface are well shielded by the PEG phase, and silanophilic adsorption of
      macromolecules is suppressed in comparison with most silica C(18) bonded phases.
      The adsorption of solutes on the -OH groups of the PEG phase seems to be low as
      well. The partition of macromolecules in favor of the PEG phase is inferior to
      that observed in case of the silica C(18) phases. The volume of the PEG bonded
      phase is small and it is supposed that the PEG chains assume flat conformation on
      the silica gel surface.

PMID- 14698239
TI  - Express analysis of explosives, chemical warfare agents and drugs with
      multicapillary column gas chromatography and ion mobility increment spectrometry.
AB  - Description of a gas chromatograph designed for express analysis of explosives
      (2,4-dinitrotoluene, 2,4,6-trinitrotoluene, pentaerythritol tetranitrate),
      chemical warfare agents (mustard gas, lewisite, sarin) and drugs (heroin, cocaine
      hydrochloride, crack) is given. The devices comprises a multicapillary
      chromatographic column and an ion mobility increment spectrometer (MCC-IMIS). The
      main analytical characteristics of an IMIS (estimated detection limit (DL),
      linear dynamic range (LDR), speed of response) and a chromatographic column
      (separation power, degree of separation, a number of possible peaks at a
      chromatogram section, divided by analysis time) are determined. The maximum value
      of DL equal to 5 pg/ml was registered for cis-alpha-LW, and the lowest one of
      0.001 pg/ml was for cocaine. The maximum value of LDR equal to 1000 was
      registered for sarin and the lowest one of 150 was for the ions of lewisite.
      Speed of response of one compound detection with the IMIS was 0.7 s.

PMID- 14698240
TI  - Plastic substrates based separation channels in electromigration techniques.
AB  - Three types of plastic materials (polyester, polyurethane and
      polymethylmethacrylate) were tested as materials for manufacturing separation
      columns (polyester and polyurethane capillaries were used) or separation channels
      (polymethylmethacrylate) in the chip format. A set of 11 fluorescein
      isothiocyanate amino acid derivatives was used as the test mixture. Using alpha
      cyclodextrin additive to the background electrolyte in the case of the chip
      separation was also tested. The main problem with all plastic separation media
      was the selectivity of the separation. The best results, practically identical
      with bare fused silica capillary, were obtained with the polymethylmethacrylate
      chip, provided that alpha-cyclodextrin in a concentration 40 mmol/l was added to
      the background electrolyte. An important observation was that in SDS containing
      background electrolyte all the plastic materials used exhibited a distinct
      electroosmotic flow, which was ascribe to the sorption of the negatively charged
      constituents of the background electrolyte to the capillary wall. Regarding the
      order in which the individual components of the test mixture were brought to the
      detector only a single change was observed. Histidine migrated in the polystyrene
      and polymethylmethacrylate separation channels more slowly than in the bare
      silica or polyurethane based capillaries.

PMID- 14698241
TI  - Micellar electrokinetic chromatography with polyelectrolyte complexes as micellar
      pseudo-stationary phases.
AB  - The separation of dansyl (DNS-AAs) and carbobenzoxy (CBZ-AAs) amino acids using
      micellar electrokinetic chromatography employing polyelectrolyte-surfactant
      complexes (PSC) formed in the reaction between polyacrylic acid (PAA) and
      dodecyltrimethylammonium bromide (DTAB) as pseudo-stationary phases was
      described. The PSCs were stabilized by hydrophobic interactions of alkyl chains
      of the surfactant ions and converted to an intramolecular micellar-like phase.
      The running buffer was a 50mM solution of sodium phosphate (pH 6.0) containing
      4.6-20.2mM PSC, in which a part of carboxyl groups of PAA was blocked by
      aliphatic amines. For the systems with 7.9mM of PAA/DTAB complex (phi=0.30, phi
      composition of water-soluble polyelectrolyte complex) as a pseudo-stationary
      phase, the peaks of six dansyl amino acids (DNS-AAs) were baseline resolved. The
      separation in this case is based on a complex distribution mechanism of the
      dansyl derivatives between the free buffer and the intramolecular micellar-like
      phase of the water-soluble PSC. On the other hand, the additives of PAA/DTAB
      complex (phi=0.30) to the running buffer does not essentially affect on the
      electrophoretic behaviour of the CBZ-AAs, the variant MEKC is not realized. The
      influence of the concentration of the complex of PAA/DTAB on the electrophoretic
      behaviour of analytes was investigated. Relative retentions and relative
      selectivities were used for describing electrophoretic behaviour of the amino
      acid derivatives.

PMID- 14698242
TI  - Simultaneous determination of fatty, dicarboxylic and amino acids based on
      derivatization with isobutyl chloroformate followed by gas chromatography
      positive ion chemical ionization mass spectrometry.
AB  - Gas chromatography-mass spectrometry (GC-MS) with positive ion chemical
      ionization (PICI) using isobutane as reagent gas was applied for analysis of
      isobutoxycarbonyl/isobutyl derivatives of 13 fatty, 6 dicarboxylic and 13 amino
      acids in a single run. For all investigated compounds (except several amino
      acids) the quasimolecular ions [MH](+) were registered. Asparagine underwent
      fragmentation via decarboxylation followed by elimination of OC(4)H(9) ([M
      117](+)), whereas serine and tyrosine produced the cluster ions
      [M+C(4)H(9)OCO](+). Estimated detection limits were 6-250 pg in the total ion
      current (TIC) mode and 3-10 times lower using the selected-ion monitoring (SIM)
      mode.

PMID- 14698243
TI  - Affinity chromatography of porcine pepsin and pepsinogen using immobilized
      ligands derived from the specific substrate for this enzyme.
AB  - Affinity chromatography of porcine protease and its zymogen was carried out on
      immobilized components of specific substrate used for the pepsin determination.
      For the immobilization of N-acetyl-L-phenylalanine and iodinated derivative of L
      tyrosine, divinyl sulfone activated Sepharose was used. Ligands with blocked
      amino group and free carboxyl one were linked to Sepharose via ethylene diamine
      spacer using carbodiimide reaction. Conditions of affinity chromatography of
      porcine pepsin and pepsinogen on the prepared carriers were optimized: the effect
      of pH, ionic strength and a nature of the buffers used on adsorption of the
      enzyme and zymogen to an affinity carrier, as well as their elution was studied.
      The following parameters were taken into consideration: capacity of the prepared
      affinity matrices, reproducibility of experiments and the enzyme stability.
      Pepsin was adsorbed to both immobilized ligands at pH 3.5-4.0; for the elution of
      the enzyme it was necessary to increase ionic strength (up to 0.5 M). For the
      adsorption of pepsinogen pH 5.2 was found to be optimum, for its desorption, an
      increase of ionic strength was used.

PMID- 14698244
TI  - Optimum separation condition of peptides in reversed-phase liquid chromatography.
AB  - An efficient optimization method was suggested to separate biologically active
      peptides by RP-HPLC. In this work, the binary mobile phase of water and
      acetonitrile was used with the buffer of trifluoroacetic acid (TFA). The elution
      profiles were calculated by the plate theory based on the linear and quadratic
      equations of retention factor, lnk=A+BF, lnk=A+BF+CF(2), and F was the vol.% of
      acetonitrile. We modified the plate theory to calculate elution profile in both
      isocratic and gradient mode. From the final calculated results, the first mobile
      phase composition was water in 0.1% TFA/acetonitrile in 0.1% TFA, 81/19vol.%,
      then after 7-8 min, the second composition of mobile phase was linearly changed
      to 79/21vol.%, and finally after 8 min, it was kept at the isocratic mode. In the
      experimental conditions, the agreement between the experimental data and the
      calculated values was relatively good.

PMID- 14698246
TI  - 3-Amino derivative of beta-cyclodextrin: thermodynamics of copper(II) complexes
      and exploitation of its enantioselectivity in the separation of amino acid
      racemates by ligand exchange capillary electrophoresis.
AB  - The systems that the 3-amino derivative of beta-cyclodextrin (CD3NH2) forms with
      the proton, the copper(II) ion and each of the enantiomers of certain amino acids
      (alanine, phenylalanine, tyrosine and tryptophan) were investigated. The
      enantioselectivity shown by the potentiometric measurements carried out on the
      phenylalanine ternary systems was exploited in capillary electrophoresis by
      ligand exchange capillary electrophoresis (LECE) to obtain the separation of
      phenylalanine racemate. The tyrosine racemate was also separated by LECE. The
      comparison between thermodynamic and capillary electrophoresis (CE) results is
      discussed, in order to get a better insight into the separation mechanism.

PMID- 14698245
TI  - Heterologous overexpression and purification of four common subunits of nuclear
      RNA polymerases I, II and III of Schizosaccharomyces pombe.
AB  - Four subunits of Schizosaccharomyces pombe RNA polymerases I-III shared by all
      three enzymes (Rpb5, Rpb8, Rpb10 and Rpc10 [Rpb12]) have been overexpressed in
      Escherichia coli expression vectors pQE or pET as hexahistidine fusions. The
      recombinant proteins have been purified to near homogeneity using metal-chelate
      affinity chromatography and gel filtration. Homogeneity and identity of the
      purified protein preparations was demonstrated by denaturing polyacrylamide gel
      electrophoresis and TOF-MALDI mass spectrometry. The proteins were obtained in
      large amounts, and their preparations are currently in use for monoclonal
      antibody production and physico-chemical studies of these individual components
      of eukaryotic transcription enzymes.

PMID- 14698247
TI  - Determination of amino acids in fodders and raw materials using capillary zone
      electrophoresis.
AB  - Two schemes were offered for analysis of amino acid contents in fodders and raw
      materials for mixed fodders by capillary zone electrophoresis (CZE). The first
      variant provides express analysis of four technologically important amino acids
      (lysine, methionine, threonine, cystine) in borate buffer on characteristic
      absorption of aminogroup (190 nm), with limits of quantitation being on average
      0.2%. The second scheme includes pre-capillary derivatization of amino acids
      using phenylisothiocyanate (PITC) and separation of phenylthiocarbamyl (PTC)
      derivatives obtained by CZE with a detection on 254 nm, which allows to widen a
      list of detectable components up to 19 (without tryptophan) and significantly
      improve detection limits down to 0.01%. Acid hydrolysis was used for a sample
      preparation. The results of analysis of fodders were compared using such methods,
      as CZE, ion exchange chromatography (amino acid analyzer) and reversed-phase (RP)
      HPLC (with gradient technique of elution).

PMID- 14698248
TI  - Application of liquid chromatography-electrospray ionization mass spectrometry
      for study of steroid-converting enzymes.
AB  - A high-performance liquid chromatography-atmospheric pressure ionization
      electrospray ionization mass spectrometry (HPLC-API-ESI-MS) method was developed
      for the analysis of steroids in a study of steroid-converting enzymes.
      Separations ware done on a Zorbax Eclipse XDB-C18 column (eluted with a linear
      methanol-water-acetic acid gradient) and identification of the steroids involved
      was done by API-ESI-MS using positive ion mode and extracted ion analysis. The
      applicability of the present method for studying steroid metabolism was proven in
      assaying two steroid-converting enzymes (20beta-hydroxysteroid dehydrogenase and
      11beta-hydroxysteroid dehydrogenase) in various biological samples (rat and
      chicken intestine, chicken oviduct).

PMID- 14698249
TI  - Peptide mapping by capillary electrophoresis with Pluronic F127.
AB  - Separation of peptides and proteins by capillary zone electrophoresis suffers
      from the interaction of these solutes with the capillary wall which results in
      the formation of broad peaks and low resolution. To minimize the protein/peptide
      capillary wall interaction we tried to use Pluronic F127, a triblock copolymer of
      the general formula (polyethylene oxide)(x)(polypropylene oxide)(y)(polyethylene
      oxide)(z) when x=106, y=70 and z=106 which can be considered a surfactant capable
      of self-association both into isotropic and anisotropic gels. The analytes
      studied were enzymatic digests (obtained by trypsin or pepsin treatment) of
      insoluble matrix proteins from avian eggshell. The best separations were obtained
      by a system exploiting 10% Pluronic F127 in 20 mmol/l phosphate buffer, pH 2.5.
      Electrophoretic peptide profiles obtained were very complex owing to the
      complicated nature of the samples (the exact composition of the proteinous
      insoluble part of the eggshell is still unknown). The separation in phosphate
      buffer only offered complex maps of incompletely resolved peaks. The use of
      Pluronic F127 distinctly improved the separation with a considerably better
      resolution regarding both the number of peaks obtained and the quality of the
      separation.

PMID- 14698250
TI  - Capillary electrophoretic separation of proteins and peptides by ion-pairing with
      heptanesulfonic acid.
AB  - Heptanesulfonic acid as ion-pairing agent was used for the separation of mixtures
      of low and high molecular mass peptides/proteins by capillary electrophoresis.
      The separation conditions used were: capillary 37 cm (30 cm to the detector) x 75
      microm i.d., voltage 10 kV, phosphate buffer 50 mmol/l, ion-pairing agent
      heptanesulfonic acid at three different concentrations, namely, 0, 20 or 100
      mmol/l, pH 2.5. The separation reflected the ion-pairing equilibria between the
      ion-pairing agent and the peptide/protein analytes. The influence of ion-pairing
      on sample mobility (running time) was more pronounced in case of the higher
      molecular peptides as compared to the low molecular ones. This difference offers
      the possibility to separate low and high molecular peptides/proteins that under
      the absence of the ion-pairing agent would co-migrate. The principle of this
      approach was demonstrated on a randomly selected set of peptides/proteins; the
      practical applicability was demonstrated on a set of CNBr peptides arising from a
      naturally occurring mixture of collagen types I and III.

PMID- 14698252
TI  - Investigation of chromatographic conditions for the separation of cefuroxime
      axetil and its geometric isomer.
AB  - The optimal chromatographic conditions for the separation of the syn- and anti
      geometric isomers of cefuroxime axetil applying RP-HPLC and micellar liquid
      chromatography (MLC) methods were investigated. The possibility to separate
      diastereoisomers of syn- and anti-cefuroxime axetil was observed. Investigations
      were performed using three columns, two classical silicas and one with hybrid
      particle technology. Three aqueous-organic and one micellar mobile phases were
      used. The best results were achieved using micellar mobile phase. Optimization
      study was performed using different micellar mobile phases. MLC method is
      sensitive and applicable in purity and stability testing.

PMID- 14698251
TI  - Cleavage of double stranded plasmid DNA by lanthanide complexes.
AB  - The use of free lanthanide ions and their complexes for plasmid DNA pBR322 and
      chromosomal DNA cleavage was studied. Plasmid pBR322 DNA was treated by
      lanthanide chlorides (Eu(3+), La(3+), Nd(3+), Pr(3+), Gd(3+)) in HEPES buffer (pH
      7.0, 7.5 and 8.0) at 24, 37, 50, 63, and 76 degrees C. The formation of linear
      and nicked plasmid forms was investigated depending on the reaction conditions.
      Heterogeneous lanthanide complexes of ethylenediamine tetraacetic acid (EDTA)
      immobilized on insoluble methacrylate support and iminodiacetic acid (IDA)
      immobilized on styrene support were used as catalysts plasmid for DNA pBR322
      cleavage, too. The temperature of reaction mixture had substantial influence on
      cleavage rate. The precipitation of DNA occurred during the measurement of
      interactions between chromosomal DNA and La(3+) ions.

PMID- 14698253
TI  - Influence of the extraction mode on the yield of some furanocoumarins from
      Pastinaca sativa fruits.
AB  - Analysis of plant material is an important task in chemotaxonomical
      investigations, in search of plants with pharmacological activity or in
      standardisation of plant drugs. The choice of optimal conditions for the analysis
      of plant material and effect of extraction method on the yield of furanocoumarins
      from Pastinaca sativa fruits were examined. The following extraction methods were
      used in experiments: exhaustive extraction in Soxhlet apparatus,
      ultrasonification (USAE) at 25 and 60 degrees C, microwave-assisted solvent
      extraction in open and closed system (MASE) and accelerated solvent extraction
      (ASE). In most cases, the yield of furanocoumarins was highest by use of ASE
      method as well as by ultrasonification at 60 degrees C.

PMID- 14698254
TI  - Liquid chromatography method for determination of mefenamic acid in human serum.
AB  - A simple, rapid and specific method for analysis of mefenamic acid (I) in serum
      by a sensitive high-performance liquid chromatography is described. Only 70
      microl of serum and a little sample work-up is required. A simple procedure of
      extraction by dichloromethane followed by evaporation to dryness under gentle
      stream of nitrogen and dissolving the dried residue in mobile phase was used. The
      mefenamic acid peak was separated from endogenous peaks on a C(8) column by a
      mobile phase of acetonitrile-water (50:50, v/v, pH 3). Mefenamic acid and
      internal standard (IS) (diclofenac) were eluted at 7.4 and 5.4 min, respectively.
      The limit of quantitation of mefenamic acid in serum was 25 ng/ml at 280 nm. The
      method was linear over the range of 25-2000 ng/ml with r(2) of 0.998. Mean
      recovery for mefenamic acid was 110%.

PMID- 14698255
TI  - Direct separation and quantitative analysis of thyroxine and triiodothyronine
      enantiomers in pharmaceuticals by high-performance liquid chromatography.
AB  - A rapid reversed-phase type HPLC method for the simultaneous separation and
      analysis of D- and L-thyroxine (D- and L-T(4)) and triiodothyronine (T(3)) was
      developed using a quinine-derived chiral stationary phase and applied for a
      quantitative assay of the enantiomeric impurity of the drugs in pharmaceutical
      formulations of levothyroxine. The influence of operating parameters has been
      studied for the optimization of the separation and also in order to gain an
      insight into the retention mechanism. Validation of the method included
      linearity, precision and accuracy which revealed R.S.D. values of <3.3% for intra
      assay precision and percent error ranging from -6 to +2.1% for various defined
      validation samples, proving satisfactory accuracy. Quantitation was performed
      over the range of 0.5-500 microg ml(-1) with limits of detection and quantitation
      lower than 0.1 and 0.5 microg ml(-1), respectively, for both analytes. Further,
      the determination of 0.1% impurity, of D-T(4) as well as L- and D-T(3) in
      levothyroxine sodium tablets proved to be feasible.

PMID- 14698256
TI  - Capillary electrophoresis method for simultaneous determination of penicillin G,
      procaine and dihydrostreptomycin in veterinary drugs.
AB  - Capillary electrophoresis method for identification and simultaneous
      determination of procaine, dihydrostreptomycin and penicillin G, present in
      multiantibiotic veterinary preparations, was elaborated. The influence of pH (5.0
      9.75) and concentration of disodium tetraborate decahydrate in running buffers
      (0.02-0.1 M) as well as temperatures (25-40 degrees C) on separation efficacy
      were analyzed. For quantitative analysis, 0.08 M borate buffer (pH 8.0) at 35
      degrees C and 15 kV were chosen. Method was validated, selectivity, precision,
      linearity, LOD, LOQ, accuracy and specificity of capillary zone electrophoresis
      (CZE) were evaluated.

PMID- 14698257
TI  - Nature of the main contaminant in the anti malaria drug primaquine diphosphate: a
      qualitative isomer analysis.
AB  - The main contaminant of primaquine (CAS 90-34-6) has been tentatively identified,
      by using two liquid chromatography (LC) methods and liquid chromatography-mass
      spectrometry (LC-MS), as the positional isomer quinocide (CAS 525-61-1). The
      first LC system was equipped with a chiral Chirex (S)-VAL and (R)-NEA column and
      the second system was equipped with an Adsorbosphere Nucleotide-Nucleoside 7
      micro column. Comparison of the main contaminant of primaquine with an authentic
      quinocide standard by using co-chromatography in both LC systems and LC-MS (mass
      fragmentation) supported the hypothesis. The toxicity of quinocide batch 17172,
      primaquine batch 16039, and the drug primaquine diphosphate batch 20107 used in
      pharmaceutical industry, and the effect of the substances on respiratory and
      electron transport chain were compared in the eucaryotic unicellular fresh water
      green alga Chlamydomonas reinhardtii as a model system. These studies suggest
      that minor amount of other related substances can contribute more to the toxicity
      of the drug primaquine diphosphate than the positional isomer quinocide.

PMID- 14698258
TI  - Direct liquid chromatography method for retinol, alpha- and gamma-tocopherols in
      rat plasma.
AB  - An HPLC method for Vitamins A and E in rat plasma has been developed. The main
      goals of the method are the small amount of sample, 50 microl, and the direct
      extraction of analytes in one step with acetone, which is a solvent compatible
      with the reverse-phase mobile phases. Recoveries, as compared with classical and
      more tedious methods, were near 100%. The method employs a Supelco Discovery C18
      column and methanol/water (95:5, v/v) as mobile phase. After being developed, the
      method was validated following ICH guidelines, with UV, fluorescence and
      electrochemical detectors. It proved to be selective, lineal, accurate and
      precise. This method greatly simplifies sample treatment and that is a critical
      point when working with a large number of samples.

PMID- 14698259
TI  - New terpenoids in cultivated and wild chamomile (in vivo and in vitro).
AB  - The effect of Chamomilla recutita (L.) Rauschert is made up by several groups of
      active substances, among which terpenoids in the inflorescences are of greatest
      importance. Among cultivated species, the Hungarian BK-2 contains more
      chamazulene in its essential oil than the German Degumil type, which is mainly
      cultivated for its (-)-alpha-bisabolol. Both components have important
      antiinflammatory activities. Among wild chamomile populations in Hungary, a
      population was found in the area of Szabadkigyos containing significant amounts
      on average 48%-of (-)-alpha-bisabolol in its inflorescence oil. In vitro cultures
      were made from this population to obtain propagation material containing a high
      number of active substances. The intact roots contained no (-)-alpha-bisabolol
      but the sesquiterpene alcohol beta-eudesmol as new compound was identified by our
      group. Sterile plantlets, cultured in vitro, were multiplied for phytochemical
      investigations. Pharmacologically important compounds of the essential oils were
      followed in great detail. The amount of in vitro cultured terpenoids and polyin
      compounds was compared with that of in vivo plants. These volatile compounds were
      identified by comparing their retention times with those of authentic standards,
      essential oils of known composition and peak enrichment. The confirmation of
      identity was done by comparison of their mass spectra with those reported in the
      literature and reference compounds. The percentage evaluation of each component
      was made by area normalisation. Gas chromatography (GC) and mass spectrometry
      (MS) showed that sterile chamomile cultures generated the most important
      terpenoid and polyin compounds characteristic of the parent plant. We identified
      germacrene-D, berkheyaradulene, 4-(2', 4', 4'-trimethyl-bicyclo[4.1.0]hept-2'-en
      3'-yl)-3-buten-2-one, geranyl-isovalerate and cedrol as new components in these
      sterile cultures.

PMID- 14698260
TI  - Determination of gamma-hydroxybutyric acid in biological fluids by using
      capillary electrophoresis with indirect detection.
AB  - gamma-Hydroxybutyric acid (GHB) is a central nervous system (CNS) depressant and
      hypnotic which, in recent times, has shown an increasing abuse either as
      recreational drug (due to its euphoric effects and ability to reduce inhibitions)
      or as doping agent (enhancer of muscle growth). Analogues of GHB, namely gamma
      butyrolactone (GBL) and 1,4-butanediol (1,4-BD), share its biological activity
      and are rapidly converted in vivo into GHB. At present, GHB and analogues are
      placed in the Schedules of Controlled Substances. Numerous intoxications in GHB
      abusers have been reported with depressive effects, seizures, coma and possibly
      death. The purpose of the present work was the development of a rapid analytical
      method based on capillary zone electrophoresis for the direct determination of
      GHB in human urine and serum at potentially toxic concentrations. Analytical
      conditions were as follows. Capillary: length 40 cm (to detector), 75 microm
      i.d.; buffer: 5.0 mM Na(2)HPO(4), 15 mM sodium barbital adjusted to pH 12 with
      1.0 M NaOH; voltage: 25 kV at 23 degrees C; indirect UV detection at 214 nm;
      injection by application of 0.5 psi for 5 s. alpha-Hydroxyisobutyric acid was
      used as internal standard (IS). Sample pretreatment was limited to 1:8 dilution.
      Under these conditions, the sensitivity was approximately 3.0 microg/ml (signal
      to-noise ratio >3). Calibration curves prepared in water, urine and serum were
      linear over concentration ranges 25-500 microg/ml with R(2)>/=0.998. Analytical
      precision was fairly good with R.S.D.<0.60% (including intraday and day-to-day
      tests). Quantitative precision in both intraday and day-to-day experiments was
      also very satisfactory with R.S.D.</=4.0%. No interferences were found neither
      from the most common "drugs of abuse" nor from endogenous compounds. In
      conclusion, capillary electrophoresis can offer a rapid, precise and accurate
      method for GHB determination of biological fluids, which could be important for
      screening purposes in clinical and forensic toxicology.

PMID- 14698261
TI  - Selective reversed-phase liquid chromatography method for the kinetic
      investigation of 3-hydroxyflavone photostability.
AB  - This paper reports a fast and accurate RP-HPLC chromatographic method for the
      simultaneous determination of 3-hydroxyflavone (3-OH F) and its photodegradation
      products. Solutions (5 x 10(-5) M) in acetonitrile (ACN) of the molecule were
      subjected to forced degradation by exposure to artificial UV-A light source
      (black-light, lambda(max) 354 nm) and the changes appearing in chromatograms were
      monitored at selected irradiation times. A multistep gradient was optimised to
      achieve complete elution of all photoproducts in the shortest analysis time. UV
      spectra recorded by the diode array detector system (285 and 340 nm) clearly
      showed the structural changes in the new species formed, with respect to the
      parent compound. The analytical method was subjected to a validation procedure in
      which linearity and range, as well as specificity, precision and accuracy were
      determined according to ICH guidelines. Quantitative evaluation of the
      photochemical process was performed on the basis of the calculated kinetic
      parameters: photodegradation rate constant k, half-life time t(0.5), time
      degradation of 10% of the drug t(0.1).

PMID- 14698262
TI  - Reversed-phase liquid chromatography analysis of imatinib mesylate and impurity
      product in Glivec capsules.
AB  - The reversed-phase high-performance liquid chromatographic (RP-HPLC) method has
      been developed and validated for the simultaneous determination of imatinib
      mesylate and of the impurity product in Glivec capsules (Novartis, Switzerland).
      Separations were performed on a X Terra 150 mm x 4.6 mm, 5 microm particle size
      column at 25 degrees C. The mobile phase was a mixture of methanol-water
      triethylamine (25:74:1, v/v/v) with flow rate of 1.0 ml min(-1). pH value of
      water-triethylamine (TEA) was adjusted to 2.4 with orthophosphoric acid before
      adding of methanol. UV detection was performed at 267 nm. Acetaminophen was used
      as an internal standard. The method was validated statistically for its
      selectivity, linearity, precision, accuracy and robustness. Due to its speed and
      accuracy, the method may be used for quality control analyses.

PMID- 14698263
TI  - Simultaneous effect of organic modifier and physicochemical parameters of
      barbiturates on their retention on a narrow-bore PGC column.
AB  - The retention time of 22 barbituric acid derivatives was measured on a narrow
      bore porous graphitized carbon (PGC) column using water-dioxane mixtures as
      mobile phases. The capacity factor (k), theoretical plate number (N), and
      asymmetry factor (AF) were calculated for each solute in each mobile phase. The
      relationships between chromatographic characteristics and physicochemical
      parameters of solutes were elucidated by stepwise regression analysis (SRA). SRA
      indicated that the binding of barbiturates to the PGC surface is of mixed
      character electrostatic and apolar interactive forces are equally involved.
      Sterical correspondence between the surface of the stationary phase and the
      solutes also exert a significant influence on the retention behavior.

PMID- 14698264
TI  - Use of the affinity chromatography principle in creating new thromboresistant
      materials.
AB  - The principle of affinity chromatography was used for preparation of
      thromboresistant bilayer coatings. The outer biospecific layer containing epsilon
      aminocaproic acid residues (from 2.2 up to 5.5 nmol/cm2) was synthesized using a
      copolymer of maleic anhydride with N-vinylpyrrolidone and L-lysine
      dihydrochloride or N-epsilon-tert-BOC-L-lysine. This surface can selectively
      adsorb plasminogen (fibrinolytic zymogen) from blood. The biospecific layer (from
      2.0 up to 3.6 microg/cm2) was applied for covering chitosan (native or modified)
      or albumin interlayer. Such bilayer coatings (BCs) were stable and represented
      the insoluble polyelectrolyte complexes. BCs were proposed for bilayer
      modification of synthetic vascular grafts, polyethylene, and other materials
      contacting with blood. This technique allowed us to significantly reduce
      thrombogenic properties of polyethylene surfaces.

PMID- 14698265
TI  - Determination of isosorbide-5-mononitrate in human plasma by high-resolution gas
      chromatography.
AB  - A method for the determination of isosorbide-5-mononitrate (5-ISMN) in human
      plasma by capillary gas chromatography with electron-capture detection was
      developed and applied to clinical samples. 9-Fluorenone was used as an internal
      standard, ethyl acetate was employed for liquid-liquid extraction. The advantage
      of the extraction procedure is the possibility of a direct injection of the
      plasma extract, without solvent removal/reconstitution of the sample. The
      precision and accuracy of the method were satisfactory in the concentration range
      10-1600 ng/ml. The lower limit of quantification was 10 ng/ml.

PMID- 14698266
TI  - Liquid chromatographic determination of total homocysteine in blood plasma with
      photometric detection.
AB  - A rapid and sensitive method for quantification of homocysteine total forms and
      glutathione levels in blood plasma via HPLC was developed. Dithiotreitol as a
      water soluble agent has been used as a reductant for both protein and nonprotein
      disulphides. Dithiotreitol reacts with the mixed disulphides under 60 degrees C
      treatment within 10 min. Reduced aminothiols and homocystein were easily
      derivated with 5,5'-dithiobis-(2-nitrobenzoic acid) and the resultant ultraviolet
      absorbance within 330 nm was detected by the HPLC method. The concentration of
      total plasma homocysteine was significantly higher in groups of patients: with
      the end stage of renal disease: 45.5+/-40.9 micromol/l (n=79), with cerebral
      vascular disorders 12.3+/-7.0 micromol/l (n=65), and with coronary
      atherosclerosis 15.4+/-10.9 micromol/l (n=15) than that in healthy subjects
      (6.2+/-1.74 micromol/l, n=20). Some major advantages of the method include:
      simultaneous measurement of both total homocysteine and total glutathione, no
      loss of oxidized form during processing of blood plasma for aminothiols
      measurement, use of protein-bound aminothiols solution as a calibrator.

PMID- 14698267
TI  - Liquid chromatography-electrospray ionization ion trap mass spectrometry for
      analysis of mesocarb and its metabolites in human urine.
AB  - A method is described for the determination of metabolites of mesocarb in human
      urine by combining gradient liquid chromatography and electrospray ionization
      (ESI)-ion trap mass spectrometry. Seven metabolites (two isomers of
      hydroxymesocarb, p-hydroxymesocarb, two isomers of dihydroxymesocarb and two
      isomers of trihydroxymesocarb) and parent drug were detected in human urine after
      the administration of a single oral dose 10 mg of mesocarb (Sydnocarb, two
      tablets of 5 mg). Various extraction techniques (free fraction, enzyme hydrolyses
      and acid hydrolyses) and their comparison were carried out for investigation of
      the metabolism of mesocarb. After extraction procedure the residue was dissolved
      in methanol and injected into the column HPLC (Zorbax SB-C18 (Narrow-Bore 2.1 x
      150 mm i.d., 5 microm particles)) with mobile phase (0.2 ml/min) of methanol/0.2
      mM ammonium acetate. Conformation of the results and identification of all
      metabolites are performed by LC-MS and LC-MS/MS. The major metabolites of
      mesocarb in urine of the human were p-hydroxylated derivative of the
      phenylcarbamoyl group of the parent drug (p-hydrohymesocarb) and dihydroxylated
      derivative of mesocarb (two isomers of dihydroxymesocarb). This analytical method
      for dihydrohymesocarb was very sensitive for discriminating the ingestion of
      mesocarb longer than the parent drug or other metabolites in human urine. The
      dihydroxymesocarb was detected in urine until 168-192 h after administration of
      the drug.

PMID- 14698268
TI  - Standardless screening of chemical warfare agents based on gas chromatographic
      data.
AB  - A method for calculation of the retention time of a compound in a temperature
      programmed mode of GC analyses is proposed. The method is based on a detailed
      consideration of thermodynamics of chromatographic process and account of the
      actual state of a capillary column. The suggested approach permits estimation of
      probability of a poisonous agent in tests by means of information stored in the
      database, eliminating a need for reference standard of such an agent.

PMID- 14698269
TI  - Needle concentrator for gas chromatographic determination of BTEX in aqueous
      samples.
AB  - A simple method of solventless extraction of volatile organic compounds (BTEX)
      from aqueous samples was developed and validated. A new arrangement of the full
      volume inside needle capillary adsorption trap (INCAT) device with Porapak Q as a
      sorbent material and wet alumina as a source of desorptive water vapour flow in a
      closed analytical system is presented. The analytical characteristics of
      developed device and of compared purge-and-trap (PTI) device for BTEX compounds
      are similar; the limits of detection as well as quantification are lower than 1
      microg l(-1).

PMID- 14698270
TI  - Multivariate analysis of fatty acids in spores of higher basidiomycetes: a new
      method for chemotaxonomical classification of fungi.
AB  - The aim of the present work was to study the possibility of using the fatty acid
      content in the basidiospores as a taxonomic tool. Basidiospores of Armillaria
      borealis, Amanita muscaria, Agaricus sylvicola, Hypholoma capnoides, Cortinarius
      nemorensis and Russula delica were used. The content of fatty acids as well as
      other substances may vary to a certain degree depending on the part (pileus,
      stipe, lamella) or stage of development of the actual basidiocarp analysed.
      Moreover, substances from fungivorous invertebrates, parasitic fungi or bacteria
      may be found in the chemical analyses of the basidiocarps. Chemotaxonomic
      conclusions may, therefore, be burdened with serious uncertainties. On the other
      hand, the ripe basidiospores are terminated structures and belong to the most
      homogenous structures encountered from a basidiocarp. Their shape, size, colour
      and ornamentation are considerably homogenous within an actual species.
      Therefore, the basidiospores are often used as a reliable differentiating
      characteristic separating species as well as taxa of higher categories. From a
      practical point of view, ripe spores are easy to obtain in relatively large
      quantities with simple techniques, and they are not so prone to decay as the
      carpophore tissue. In the present study, gas chromatography (GC) and gas
      chromatography-mass spectrometry (GC-MS), after methanolysis of the fungus
      spores, were used to map essential fatty acids in basidiomycetes. Gas
      chromatography and gas chromatography-mass spectrometry revealed the presence of
      fatty acids of C12:0-C24:0 size in the basidiospores of these higher
      basidiomycetes. The major fatty acid in H. capnoides is C18:2, and the major
      fatty acid in the other species is C18:1. The basidiospores proved to be a good
      source of fatty acids for chemotaxonomic investigations of agarics.

PMID- 14698271
TI  - Optimization of a matrix solid-phase dispersion method for the determination
      analysis of carbendazim residue in plant material.
AB  - The objective of this paper was to prove that matrix solid-phase dispersion
      (MSPD) coupled with high performance liquid chromatography (HPLC) and column
      switching could be used for the determination and quantification of carbendazim
      residue in plant samples. By comparing results obtained after optimization of the
      extraction conditions on an acidic silica gel column, it was determined that
      sorption and retention of carbendazim were achieved via specific interactions.
      The method of standard additions was used for quantitative analysis. Its
      performance was evaluated and validated: the detection limit (UV-Vis detection at
      lambda=279 nm) was 0.02 microg/g, the relative standard deviations (R.S.D.) were
      between 2.7 and 4.1% and the recoveries were ranging from 84.3 to 90.7% at the
      0.04, 0.08 and 0.1 microg/g fortification levels. The method was successfully
      tested on cereal samples, and the results obtained with the present off-line MSPD
      HPLC procedure were found to compare well with those obtained with procedure
      involving LLE.

PMID- 14698272
TI  - Reversed-phase liquid chromatographic-mass spectrometric determination of
      microcystin-LR in cyanobacteria blooms under alkaline conditions.
AB  - Reversed-phase HPLC coupled to the atmospheric pressure ionization-electrospray
      ionization (API-ESI) MS was used for microcystin-LR detection and quantitation in
      samples of dried Microcystis aeruginosa cells. An alkaline linear gradient (20
      mmol/l ammonium hydroxide-acetonitrile, pH 9.7) was used for elution of the toxic
      peptides. Limit of detection was 1 microg/ml (20 ng per injection) in the scan
      mode of MS and 0.1 microg/ml (2 ng per injection) in the case of selective ion
      monitoring.

PMID- 14698273
TI  - Simultaneous determination of fluoride, chloride, nitrite, bromide, nitrate,
      phosphate and sulfate in aqueous solutions at 10(-9) to 10(-8)% level by ion
      chromatography.
AB  - The method of simultaneous determination of F-, Cl-, NO2-, Br-, NO3-, HPO(4)2-,
      SO(4)2- ions on trace level by IC using preliminary concentration and water
      removal from concentrating column was proposed. Detection limits were 10(-9) to
      10(-8)% for sample volume 10 ml depending on the anion.

PMID- 14698274
TI  - Gas chromatography-mass spectrometry with headspace for the analysis of volatile
      organic compounds in waste water.
AB  - Headspace analysis combined with high-resolution gas chromatography and detection
      by mass spectrometry was evaluated for the analysis of 53 volatile organic
      compounds (VOCs) in river waters, waste waters and treated water samples down to
      0.1 microgl(-1) concentration levels. The conditions optimised included sample
      thermostatting time and temperature, autosampler parameters and the nature of
      salt, added to the sample. The pollutions origin and their seasonal rippling have
      been done. It was shown that the content of VOCs in river water mainly correlates
      to the content of these compounds in waste waters, which shows the anthropogenic
      character of the pollutions.

PMID- 14698275
TI  - Genetic knock out of 60kD Ro (or SSA), a common lupus autoantigen, induces lupus.
AB  - Systemic lupus erythematosus (SLE) could have the most complicated phenotype and
      the most diverse genetics of any genetically complex human disease. Recent
      research shows that genetic ablation of the gene encoding 60kD Ro, a common
      autoantigen for SLE patients, results in an SLE-like illness in Ro-/- mice. These
      data add to the expanding cooperation between mouse and human SLE genetic studies
      and are the first in which ablation of an autoantigen induces an autoimmune
      disease.

PMID- 14698276
TI  - Inflammation: the link between insulin resistance, obesity and diabetes.
AB  - Recent data have revealed that the plasma concentration of inflammatory
      mediators, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL
      6), is increased in the insulin resistant states of obesity and type 2 diabetes,
      raising questions about the mechanisms underlying inflammation in these two
      conditions. It is also intriguing that an increase in inflammatory mediators or
      indices predicts the future development of obesity and diabetes. Two mechanisms
      might be involved in the pathogenesis of inflammation. Firstly, glucose and
      macronutrient intake causes oxidative stress and inflammatory changes. Chronic
      overnutrition (obesity) might thus be a proinflammatory state with oxidative
      stress. Secondly, the increased concentrations of TNF-alpha and IL-6, associated
      with obesity and type 2 diabetes, might interfere with insulin action by
      suppressing insulin signal transduction. This might interfere with the anti
      inflammatory effect of insulin, which in turn might promote inflammation.

PMID- 14698277
TI  - Distinguishing the tritope from the interaction antigen models.

PMID- 14698279
TI  - On the origins of adaptive immunity: innate immune receptors join the tale.
AB  - Among members of the Ig superfamily (IgSF), antigen receptors have the unique
      capacity to rearrange their variable domains, thereby creating an extensive
      repertoire for antigen recognition. It is assumed that antigen receptors evolved
      from a non-rearranging IgSF member by insertion of a transposable element.
      Although the nature of this predecessor is unknown, two multigene families of
      innate immune receptors that bear a close structural resemblance to antigen
      receptor chains have been identified in mammals and bony fish, respectively:
      signal-regulatory proteins (SIRPs) and novel immune-type receptors (NITRs).
      Members of both families encode V-set Ig domains with a typical antigen receptor
      like joining (J) motif and possess the potential to signal through immunoreceptor
      tyrosine-based inhibition motifs (ITIMs) or immunoreceptor tyrosine-based
      activation motifs (ITAMs). By analogy to the T-cell receptor (TCR) and certain
      innate receptors [e.g. killer cell inhibitory receptors (KIRs)] that recognize
      MHC molecules, SIRP members regulate immune function by interaction with broadly
      expressed 'self' ligands. We propose the existence of an evolutionary and
      functional link between innate and adaptive immune receptors that sheds light on
      the nature of the antigen receptor predecessor(s).

PMID- 14698280
TI  - Stressed-out B cells? Plasma-cell differentiation and the unfolded protein
      response.
AB  - Plasma cells operate as factories where large quantities of Ig heavy and light
      chains are made and assembled into functional antibodies. The finished products
      are shipped out with impressive efficiency. A major component of the machinery
      necessary for high-rate antibody secretion is an elaborate network of endoplasmic
      reticulum (ER), the site of antibody biosynthesis. Recent discoveries have
      provided insights into how this expansive secretory machinery is built, equipped
      and maintained. The unfolded protein response (UPR) pathway, a stress-induced
      signaling cascade emanating from the ER, regulates the expression and activity of
      X-box binding protein 1, a transcription factor required for plasma-cell
      development. The UPR pathway therefore senses conditions in the ER--the very
      compartment where antibodies are formed--and directs events required for humoral
      immunity.

PMID- 14698281
TI  - The double life of NK receptors: stimulation or co-stimulation?
AB  - Stimulatory killer immunoglobulin-like receptors, NKG2D and stimulatory receptors
      of the CD94-NKG2 family have duplicity in function. On natural killer (NK) cells,
      these receptors act as independent and competent recognition units. Stimulatory
      NK receptors also appear on subsets of effector T cells, particularly those that
      have replicated extensively. When expressed on T cells, they amplify signals
      mediated through the T-cell antigen receptor and, thus, function as co
      stimulatory, but not direct stimulatory, molecules. One mechanism responsible for
      this dichotomy is the differential expression of adaptor molecules. This
      duplicity in function, which is not seen for other co-stimulatory molecules, is
      responsible for the unique context information provided by the NK receptors, and
      it could explain their involvement in chronic inflammation and autoimmunity.

PMID- 14698282
TI  - Adenosine: an endogenous regulator of innate immunity.
AB  - Although inflammatory and immunological reactions protect the host from invasion
      by microorganisms and eliminate debris at sites of tissue injury, they can also
      be responsible for significant tissue damage. Thus, regulatory mechanisms that
      limit damage from an overly exuberant immune response have evolved. It is
      increasingly apparent that adenosine, a purine nucleoside that is elaborated at
      injured and inflamed sites, has a central role in the regulation of inflammatory
      responses and in limiting inflammatory tissue destruction. Adenosine, called a
      'retaliatory metabolite' because it is a regulatory autocoid that is generated as
      a result of cellular injury or stress, interacts with specific G protein-coupled
      receptors on inflammatory and immune cells to regulate their function. The
      effects of adenosine, acting at its receptors, on the functions of the cells that
      mediate innate immune responses, will be reviewed.

PMID- 14698283
TI  - The lung as a privileged site for the beneficial actions of PGE2.
AB  - Prostaglandin E2 (PGE2) is commonly considered a potent proinflammatory mediator
      and is involved in several inflammatory diseases. In the lung, as opposed to many
      other parts of the body, PGE2 has a role in limiting the immune-inflammatory
      response as well as tissue repair processes. Understanding the full implications
      of the regulatory role of PGE2 and how beneficial processes, such as inflammation
      and tissue repair, become dysregulated to the point of causing disease, might
      disclose new perspectives in the treatment of pulmonary diseases.

PMID- 14698284
TI  - NK cell and DC interactions.
AB  - Recent interest has focused on interactions between natural killer (NK) cells and
      dendritic cells (DCs). In vitro and in vivo studies have demonstrated various
      effects of NK-DC interactions, including activation and cytokine production,
      maturation of DCs and NK-cell lysis of certain autologous DCs. These interactions
      are important during an immune response in vivo, however, it remains unclear
      where in the body NK cells and DCs might interact and whether observed in vitro
      crosstalk between these cell types happens in vivo. We propose evidence for at
      least two potential locations of in vivo interactions for human NK cells and DCs,
      including sites of inflammation and lymph nodes.

PMID- 14698285
TI  - Are residues in a protein folding nucleus evolutionarily conserved?
AB  - Protein is the working molecule of the cell, and evolution is the hallmark of
      life. It is important to understand how protein folding and evolution influence
      each other. Several studies correlating experimental measurement of residue
      participation in folding nucleus and sequence conservation have reached different
      conclusions. These studies are based on assessment of sequence conservation at
      folding nucleus sites using entropy or relative entropy measurement derived from
      multiple sequence alignment. Here we report analysis of conservation of folding
      nucleus using an evolutionary model alternative to entropy-based approaches. We
      employ a continuous time Markov model of codon substitution to distinguish
      mutation fixed by evolution and mutation fixed by chance. This model takes into
      account bias in codon frequency, bias-favoring transition over transversion, as
      well as explicit phylogenetic information. We measure selection pressure using
      the ratio omega of synonymous versus non-synonymous substitution at individual
      residue site. The omega-values are estimated using the PAML method, a maximum
      likelihood estimator. Our results show that there is little correlation between
      the extent of kinetic participation in protein folding nucleus as measured by
      experimental phi-value and selection pressure as measured by omega-value. In
      addition, two randomization tests failed to show that folding nucleus residues
      are significantly more conserved than the whole protein, or the median omega
      value of all residues in the protein. These results suggest that at the level of
      codon substitution, there is no indication that folding nucleus residues are
      significantly more conserved than other residues. We further reconstruct
      candidate ancestral residues of the folding nucleus and suggest possible test
      tube mutation studies for testing folding behavior of ancient folding nucleus.

PMID- 14698286
TI  - The translation initiation functions of IF2: targets for thiostrepton inhibition.
AB  - Bacterial translation initiation factor IF2 was localized on the ribosome by rRNA
      cleavage using free Cu(II):1,10-orthophenanthroline. The results indicated
      proximity of IF2 to helix 89, to the sarcin-ricin loop and to helices 43 and 44,
      which constitute the "L11/thiostrepton" stem-loops of 23S rRNA. These findings
      prompted an investigation of the L11 contribution to IF2 activity and a re
      examination of the controversial issue of the effect on IF2 functions of
      thiostrepton, a peptide antibiotic known primarily as a powerful inhibitor of
      translocation. Ribosomes lacking L11 were found to have wild-type capacity to
      bind IF2 but a strongly reduced ability to elicit its GTPase activity. We found
      that thiostrepton caused a faster recycling of this factor on and off the 70S
      ribosomes and 50S subunits, which in turn resulted in an increased rate of the
      multiple turnover IF2-dependent GTPase. Although thiostrepton did not inhibit the
      P-site binding of fMet-tRNA, the A-site binding of the EF-Tu-GTP-Phe-tRNA or the
      activity of the ribosomal peptidyl transferase center (as measured by the
      formation of fMet-puromycin), it severely inhibited IF2-dependent initiation
      dipeptide formation. This inhibition can probably be traced back to a
      thiostrepton-induced distortion of the ribosomal-binding site of IF2, which leads
      to a non-productive interaction between the ribosome and the aminoacyl-tRNA
      substrates of the peptidyl transferase reaction. Overall, our data indicate that
      the translation initiation function of IF2 is as sensitive as the translocation
      function of EF-G to thiostrepton inhibition.

PMID- 14698287
TI  - Identification of the subunit-subunit interface of Xenopus Rad51.1 protein:
      similarity to RecA.
AB  - Rad51, like its prokaryotic homolog RecA, forms a helical filament for homologous
      DNA recombination and recombinational DNA repair. Comparison of the three
      dimensional structures of human Rad51 and Escherichia coli RecA indicated that
      the tyrosine residue at position 191 in human Rad51 lies at the centre of a
      putative subunit-subunit contact interface. We inserted a tryptophan residue as a
      fluorescent probe at the corresponding position in Xenopus Rad51.1 and found that
      its fluorescence depended upon the protein concentration, indicating that the
      residue is truly in the subunit-subunit interface. We also found that 3 M urea,
      which promoted the dissociation of Rad51 filament without complete unfolding of
      the protein, exposed the tryptophan residue to solvent. The fluorescence was not
      modified by binding to DNA and only slightly modified by ATP, indicating that the
      same site is used for formation of the active ATP-Rad51-DNA filament. The slight
      changes in fluorescence caused by ATP and ADP suggest that the subunit-subunit
      contact is altered, leading to the elongation of the filament by these
      nucleotides, as with the RecA filament. Thus, Rad51 forms filaments by subunit
      subunit contact much like RecA does.

PMID- 14698289
TI  - GTP-dependent recognition of the methionine moiety on initiator tRNA by
      translation factor eIF2.
AB  - Eukaryotic translation initiation factor 2 (eIF2) is a G-protein that functions
      as a central switch in the initiation of protein synthesis. In its GTP-bound
      state it delivers the methionyl initiator tRNA (Met-tRNA(i)) to the small
      ribosomal subunit and releases it upon GTP hydrolysis following the recognition
      of the initiation codon. We have developed a complete thermodynamic framework for
      the assembly of the Saccharomyces cerevisiae eIF2.GTP.Met-tRNA(i) ternary complex
      and have determined the effect of the conversion of GTP to GDP on eIF2's affinity
      for Met-tRNA(i) in solution. In its GTP-bound state the factor forms a positive
      interaction with the methionine moiety on Met-tRNA(i) that is disrupted when GTP
      is replaced with GDP, while contacts between the factor and the body of the tRNA
      remain intact. This positive interaction with the methionine residue on the tRNA
      may serve to ensure that only charged initiator tRNA enters the initiation
      pathway. The toggling on and off of the factor's interaction with the methionine
      residue is likely to play an important role in the mechanism of initiator tRNA
      release upon initiation codon recognition. In addition, we show that the
      conserved base-pair A1:U72, which is known to be a critical identity element
      distinguishing initiator from elongator methionyl tRNA, is required for
      recognition of the methionine moiety by eIF2. Our data suggest that a role of
      this base-pair is to orient the methionine moiety on the initiator tRNA in its
      recognition pocket on eIF2.

PMID- 14698288
TI  - Interactions at the dimer interface influence the relative efficiencies for
      purine nucleotide synthesis and pyrophosphorolysis in a
      phosphoribosyltransferase.
AB  - Enzymes that salvage 6-oxopurines, including hypoxanthine
      phosphoribosyltransferases (HPRTs), are potential targets for drugs in the
      treatment of diseases caused by protozoan parasites. For this reason, a number of
      high-resolution X-ray crystal structures of the HPRTs from protozoa have been
      reported. Although these structures did not reveal why HPRTs need to form dimers
      for catalysis, they revealed the existence of potentially relevant interactions
      involving residues in a loop of amino acid residues adjacent to the dimer
      interface, but the contributions of these interactions to catalysis remained
      poorly understood. The loop, referred to as active-site loop I, contains an
      unusual non-proline cis-peptide and is composed of residues that are structurally
      analogous with Leu67, Lys68, and Gly69 in the human HPRT. Functional analyses of
      site-directed mutations (K68D, K68E, K68N, K68P, and K68R) in the HPRT from
      Trypanosoma cruzi, etiologic agent of Chagas' disease, show that the side-chain
      at position 68 can differentially influence the K(m) values for all four
      substrates as well as the k(cat) values for both IMP formation and
      pyrophosphorolysis. Also, the results for the K68P mutant are inconsistent with a
      cis-trans peptide isomerization-assisted catalytic mechanism. These data,
      together with the results of structural studies of the K68R mutant, reveal that
      the side-chain of residue 68 does not participate directly in reaction chemistry,
      but it strongly influences the relative efficiencies for IMP formation and
      pyrophosphorolysis, and the prevalence of lysine at position 68 in the HPRT of
      the majority of eukaryotes is consistent with there being a biological role for
      nucleotide pyrophosphorolysis.

PMID- 14698290
TI  - The rad50 signature motif: essential to ATP binding and biological function.
AB  - The repair of double-strand breaks in DNA is an essential process in all
      organisms, and requires the coordinated activities of evolutionarily conserved
      protein assemblies. One of the most critical of these is the Mre11/Rad50 (M/R)
      complex, which is present in all three biological kingdoms, but is not well
      understood at the biochemical level. Previous structural analysis of a Rad50
      homolog from archaebacteria illuminated the catalytic core of the enzyme, an ATP
      binding domain related to the ABC transporter family of ATPases. Here, we present
      the crystallographic structure of the Rad50 mutant S793R. This missense signature
      motif mutation changes the key serine residue in the signature motif that is
      conserved among Rad50 homologs and ABC ATPases. The S793R mutation is analogous
      to the mutation S549R in the cystic fibrosis transmembrane conductance regulator
      (CFTR) that results in cystic fibrosis. We show here that the serine to arginine
      change in the Rad50 protein prevents ATP binding and disrupts the communication
      among the other ATP-binding loops. This structural change, in turn, alters the
      communication between Rad50 monomers and thus prevents Rad50 dimerization. The
      equivalent mutation was made in the human Rad50 gene, and the resulting mutant
      protein did form a complex with Mre11 and Nbs1, but was specifically deficient in
      all ATP-dependent enzymatic activities. This signature motif structure-function
      homology extends to yeast, because the same mutation introduced into the
      Saccharomyces cerevisiae RAD50 gene generated an allele that failed to complement
      a rad50 deletion strain in DNA repair assays in vivo. These structural and
      biochemical results extend our understanding of the Rad50 catalytic domain and
      validate the use of the signature motif mutant to test the role of Rad50 ATP
      binding in diverse organisms.

PMID- 14698291
TI  - Most chloroplast DNA of maize seedlings in linear molecules with defined ends and
      branched forms.
AB  - We used pulsed-field gel electrophoresis, restriction fragment mapping, and
      fluorescence microscopy of individual DNA molecules to analyze the structure of
      chloroplast DNA (cpDNA) from shoots of ten to 14 day old maize seedlings. We find
      that most of the cpDNA is in linear and complex branched forms, with only 3-4% as
      circles. We find the ends of linear genomic monomers and head-to-tail (h-t)
      concatemers within inverted repeat sequences (IRs) near probable origins of
      replication, not at random sites as expected from broken circles. Our results
      predict two major and three minor populations of linear molecules, each with
      different ends and putative origins of replication. Our mapping data predict
      equimolar populations of h-t linear concatemeric molecules differing only in the
      relative orientation (inversion) of the single copy regions. We show how
      recombination during replication can produce h-t linear concatemers containing an
      inversion of single copy sequences that has for 20 years been attributed to
      recombinational flipping between IRs in a circular chromosome. We propose that
      replication is initiated predominantly on linear, not circular, DNA, producing
      multi-genomic branched chromosomes and that most replication involves strand
      invasion of internal regions by the ends of linear molecules, rather than the
      generally accepted D-loop-to-theta mechanism. We speculate that if the minor
      amount of cpDNA in circular form is useful to the plant, its contribution to
      chloroplast function does not depend on the circularity of these cpDNA molecules.

PMID- 14698292
TI  - Inhibition of E6-induced degradation of its cellular substrates by novel blocking
      peptides.
AB  - The E6 oncoprotein derived from the tumour-associated human papillomavirus (HPV)
      types induces the ubiquitin-mediated degradation of several cellular proteins by
      conjugating them with the cellular ubiquitin ligase E6-AP. This is a HECT domain
      containing ligase that was originally identified through its involvement in the
      E6-mediated degradation of the cellular tumour suppressor protein p53. Here we
      have investigated, in more detail, the nature of the E6/E6-AP interaction using
      binding peptides isolated from an E6-specific library. The selected peptides were
      either predicted or shown to have an alpha-helical core resembling the E6-binding
      motif on E6-AP, as well as amino acid alterations that increased their affinity
      for E6. These peptides were potent inhibitors of the E6/E6-AP interaction.
      Further analysis of the effects of these peptides on the ability of E6 to direct
      the proteolytic degradation of its various substrates, including p53, Dlg and the
      MAGI family of proteins, as well as using E6-AP immunodepletion, revealed
      striking differences in the mechanism by which E6 targets its cellular substrates
      for degradation. These results suggest that the site on E6 bound by E6-AP is also
      most likely occupied by other, as yet unidentified, ubiquitin ligases.

PMID- 14698293
TI  - The invertase inhibitor Nt-CIF from tobacco: a highly thermostable four-helix
      bundle with an unusual N-terminal extension.
AB  - Plant invertases are sucrolytic enzymes essential for plant metabolism and
      development. Enzyme activity is regulated on a posttranslational level via
      inhibitory proteins, referred to as invertase inhibitors. Ectopic expression of
      invertase inhibitors in crop plants has high biotechnological potential. However,
      little biochemical and up to now no detailed structural information is available
      about this class of plant regulatory proteins. Here, we present the crystal
      structure of the cell wall-associated invertase inhibitor Nt-CIF from tobacco at
      a resolution of 1.87A. The structural model reveals an asymmetric four-helix
      bundle with an uncommon N-terminal extension that appears to be critical for the
      structural integrity of the protein. Structure analysis of a second crystal form
      grown in the presence of CdCl(2) reveals two metal binding sites. Nt-CIF is
      highly thermostable and retains full inhibitory activity after cooling to ambient
      temperatures. The structure of Nt-CIF provides the first three-dimensional
      information source for the posttranslational regulation of plant invertases.
      Based on the recently discovered sequence homology between inhibitors of
      invertases and pectin methylesterases, our structural model is likely to
      represent a scaffold also used for the regulation of the latter enzymes, which do
      not share sequence similarity with invertases. Thus, our structural model sets
      the 3D-stage for the investigation of posttranslational regulation of invertases
      as well as pectin methylesterases.

PMID- 14698294
TI  - Effect of different anti-Abeta antibodies on Abeta fibrillogenesis as assessed by
      atomic force microscopy.
AB  - Extensive data suggest that the conversion of the amyloid-beta (Abeta) peptide
      from soluble to insoluble forms is a key factor in the pathogenesis of
      Alzheimer's disease (AD). In recent years, atomic force microscopy (AFM) has
      provided useful insights into the physicochemical processes involving Abeta
      morphology, and it can now be used to explore factors that either inhibit or
      promote fibrillogenesis. We used ex situ AFM to explore the impact of anti-Abeta
      antibodies directed against different domains of Abeta on fibril formation. For
      the AFM studies, two monoclonal antibodies (m3D6 and m266.2) were incubated in
      solution with Abeta(1-42) with a molar ratio of 1:10 (antibody to Abeta) over
      several days. Fibril formation was analyzed quantitatively by determining the
      number of fibrils per microm(2) and by aggregate size analysis. m3D6, which is
      directed against an N-terminal domain of Abeta (amino acid residues 1-5) slowed
      down fibril formation. However, m266.2, which is directed against the central
      domain of Abeta (amino acid residues 13-28) appeared to completely prevent the
      formation of fibrils over the course of the experiment. Inhibition of fibril
      formation by both antibodies was also confirmed by thioflavin-T (ThT)
      fluorescence experiments carried out with Abeta(1-40) incubated for five days.
      However, unlike AFM results, ThT did not differentiate between the samples
      incubated with m3D6 versus m266.2. These results indicate that AFM can be not
      only reliably used to study the effect of different molecules on Abeta
      aggregation, but that it can provide additional information such as the role of
      epitope specificity of antibodies as potential inhibitors of fibril formation.

PMID- 14698295
TI  - Evolution of aldolase antibodies in vitro: correlation of catalytic activity and
      reaction-based selection.
AB  - Aldolase antibodies that operate via an enamine mechanism were developed by in
      vitro selection. Antibody Fab phage display libraries were created where the
      catalytic active site residues of aldolase antibodies 38C2 and 33F12 were
      combined with a naive human antibody V gene repertoire. Selection from these
      libraries with 1,3-diketones covalently trapped the amino groups of reactive
      lysine residues by formation of stable enaminones. The selected aldolase
      antibodies retained the essential catalytic lysine residue and its function in
      altered and humanized primary antibody structures. The substrate specificity of
      the aldolase antibodies was directly related to the structure of the diketone
      used for selection. The k(cat) values of the antibody-catalyzed retro-aldol
      reactions were correlated with the K(d) values, i.e. the reactivities of the
      selected aldolase antibodies for the corresponding diketones. Antibodies that
      bound to the diketone with a lower K(d) value displayed a higher k(cat) value in
      the retro-aldol reaction, and a linear relationship was observed in the plots of
      logk(cat) versus logK(d). These results indicate that selections with diketones
      directed the evolution of aldolase antibodies in vitro that operate via an
      enamine mechanism. This strategy provides a route to tailor-made aldol catalysts
      with different substrate specificities.

PMID- 14698296
TI  - Structure of the integrin alpha2beta1-binding collagen peptide.
AB  - We have determined the 1.8A crystal structure of a triple helical integrin
      binding collagen peptide (IBP) with sequence (Gly-Pro-Hyp)(2)-Gly-Phe-Hyp-Gly-Glu
      Arg-(Gly-Pro-Hyp)(3). The central GFOGER hexapeptide is recognised specifically
      by the integrins alpha2beta1, alpha1beta1, alpha10beta1 and alpha11beta1. These
      integrin/collagen interactions are implicated in a number of key physiological
      processes including cell adhesion, cell growth and differentiation, and
      pathological states such as thrombosis and tumour metastasis. Comparison of the
      IBP structure with the previously determined structure of an identical collagen
      peptide in complex with the integrin alpha2-I domain (IBP(c)) allows the first
      detailed examination of collagen in a bound and an unbound state. The IBP
      structure shows a direct and a water-mediated electrostatic interaction between
      Glu and Arg side-chains from adjacent strands, but no intra-strand interactions.
      The interactions between IBP Glu and Arg side-chains are disrupted upon integrin
      binding. A comparison of IBP and IBP(c) main-chain conformation reveals the
      flexible nature of the triple helix backbone in the imino-poor GFOGER region.
      This flexibility could be important to the integrin-collagen interaction and
      provides a possible explanation for the unique orientation of the three GFOGER
      strands observed in the integrin-IBP(c) complex crystal structure.

PMID- 14698297
TI  - Temperature dependence of the thermodynamics of helix-coil transition.
AB  - The temperature-induced helix to coil transition in a series of host peptides was
      monitored using circular dichroism spectroscopy (CD) and differential scanning
      calorimetry (DSC). Combination of these two techniques allowed direct
      determination of the enthalpy of helix-coil transition for the studied peptides.
      It was found that the enthalpy of the helix-coil transition differs for different
      peptides and this difference is related to the difference in the temperature for
      the midpoint of helix-coil transition. The enthalpy of the helix-coil transition
      decreases with the increase in temperature, thus providing the first experimental
      estimate for the heat capacity changes upon helix-coil transition, DeltaC(p). The
      values for DeltaC(p) of helix-coil transition are found to be negative, which is
      in contrast to the positive DeltaC(p) for protein unfolding. Analysis suggests
      that this negative DeltaC(p) of helix-coil transition is due to the exposure of
      the polar peptide backbone to solvent upon helix unfolding.

PMID- 14698298
TI  - Two types of Alzheimer's beta-amyloid (1-40) peptide membrane interactions:
      aggregation preventing transmembrane anchoring versus accelerated surface fibril
      formation.
AB  - The 39-42 amino acid long, amphipathic amyloid-beta peptide (Abeta) is one of the
      key components involved in Alzheimer's disease (AD). In the neuropathology of AD,
      Abeta presumably exerts its neurotoxic action via interactions with neuronal
      membranes. In our studies a combination of 31P MAS NMR (magic angle spinning
      nuclear magnetic resonance) and CD (circular dichroism) spectroscopy suggest
      fundamental differences in the functional organization of supramolecular Abeta(1
      40) membrane assemblies for two different scenarios with potential implication in
      AD: Abeta peptide can either be firmly anchored in a membrane upon proteolytic
      cleavage, thereby being prevented against release and aggregation, or it can have
      fundamentally adverse effects when bound to membrane surfaces by undergoing
      accelerated aggregation, causing neuronal apoptotic cell death. Acidic lipids can
      prevent release of membrane inserted Abeta(1-40) by stabilizing its hydrophobic
      transmembrane C-terminal part (residue 29-40) in an alpha-helical conformation
      via an electrostatic anchor between its basic Lys28 residue and the negatively
      charged membrane interface. However, if Abeta(1-40) is released as a soluble
      monomer, charged membranes act as two-dimensional aggregation-templates where an
      increasing amount of charged lipids (possible pathological degradation products)
      causes a dramatic accumulation of surface-associated Abeta(1-40) peptide followed
      by accelerated aggregation into toxic structures. These results suggest that two
      different molecular mechanisms of peptide-membrane assemblies are involved in
      Abeta's pathophysiology with the finely balanced type of Abeta-lipid interactions
      against release of Abeta from neuronal membranes being overcompensated by an
      Abeta-membrane assembly which causes toxic beta-structured aggregates in AD.
      Therefore, pathological interactions of Abeta peptide with neuronal membranes
      might not only depend on the oligomerization state of the peptide, but also the
      type and nature of the supramolecular Abeta-membrane assemblies inherited from
      Abeta's origin.

PMID- 14698299
TI  - beta2-microglobulin H31Y variant 3D structure highlights the protein natural
      propensity towards intermolecular aggregation.
AB  - beta2-Microglobulin (beta2m) is the non-covalently bound light chain of the human
      class I major histocompatibility complex (MHC-I). The natural turnover of MHC-I
      gives rise to the release of beta2m into plasmatic fluids and to its catabolism
      in the kidney. beta2m dissociation from the heavy chain of the complex is a
      severe complication in patients receiving prolonged hemodialysis. As a
      consequence of renal failure, the increasing beta2m concentrations can lead to
      deposition of the protein as amyloid fibrils. Here we characterize the His31-
      >Tyr human beta2m mutant, a non-natural form of beta2m that is more stable than
      the wild-type protein, displaying a ten-fold acceleration of the slow phase of
      folding. We report the 2.9A resolution crystal structure and the NMR
      characterization of the mutant beta2m, focussing on selected structural features
      and on the molecular packing observed in the crystals. Juxtaposition of the four
      mutant beta2m molecules contained in the crystal asymmetric unit, and specific
      hydrogen bonds, stabilize a compact protein assembly. Conformational
      heterogeneity of the four independent molecules, some of their mutual
      interactions and partial unpairing of the N-terminal beta-strand in one protomer
      are in keeping with the amyloidogenic properties displayed by the mutant beta2m.

PMID- 14698301
TI  - A novel database of disulfide patterns and its application to the discovery of
      distantly related homologs.
AB  - Disulfide bonds are conserved strongly among proteins of related structure and
      function. Despite the explosive growth of protein sequence databases and the vast
      numbers of sequence search tools, no tool exists to draw relations between the
      disulfide patterns of homologous proteins. We present a comprehensive database of
      disulfide bonding patterns and a search method to find proteins with similar
      disulfide patterns. The disulfide database was constructed using disulfide
      annotations extracted from SwissProt, and was expanded significantly from 16,736
      to 94,499 disulfide-containing domains by an inference method that combines
      SwissProt annotations with Pfam multiple alignments. To search the database, we
      define a disulfide description, called the disulfide signature, which encodes
      both spacings between cysteine residues and cysteine connectivity. A web tool was
      developed that allows users to search for related disulfide patterns and for
      subpatterns resulting from the removal of one or more disulfides from the
      pattern. We explore the possibility of using disulfide pattern conservation to
      identify protein homologs that are undetectable by PSI-BLAST. Examples include
      the homology between a sea anemone antihypertensive/antiviral protein and a sea
      anemone neurotoxin, and the homology between tick anticoagulant peptide and
      bovine trypsin inhibitor. In both examples, there is a clear structural
      similarity and a functional relationship. We used the database to find structural
      homologs for the Cripto CFC domain. The identification of a von Willebrand Factor
      C (VWFC)-like domain agrees with its functional role and explains mutation data.
      We believe that the rapid increase in structure determinations arising from
      structural genomics efforts and advances in mass spectrometry techniques will
      greatly increase the number of disulfide annotations. This information will
      become a valuable resource for structural and functional annotations of proteins.
      The availability of a searchable disulfide pattern database will thus provide a
      powerful new addition to existing homolog discovery methods.

PMID- 14698300
TI  - Folding mechanism of FIS, the intertwined, dimeric factor for inversion
      stimulation.
AB  - FIS, the factor for inversion stimulation, from Escherichia coli and other
      enteric bacteria, is an interwined alpha-helical homodimer. Size exclusion
      chromatography and static light scattering measurements demonstrated that FIS is
      predominately a stable dimer at the concentrations (1-10 microM monomer) and
      buffer conditions employed in this study. The folding and unfolding of FIS were
      studied with both equilibrium and kinetic methods by circular dichroism using
      urea and guanidinium chloride (GdmCl) as the perturbants. The equilibrium folding
      is reversible and well-described by a two-state folding model, with stabilities
      at 10 degrees C of 15.2 kcal mol(-1) in urea and 13.5 kcal mol(-1) in GdmCl. The
      kinetic data are consistent with a two-step folding reaction where the two
      unfolded monomers associate to a dimeric intermediate within the mixing time for
      the stopped-flow instrument (<5 ms), and a slower, subsequent folding of the
      dimeric intermediate to the native dimer. Fits of the burst phase amplitudes as a
      function of denaturant showed that the free energy for the formation of the
      dimeric intermediate constitutes the majority of the stability of the folding
      (9.6 kcal mol(-1) in urea and 10.5 kcal mol(-1) in GdmCl). Folding-to-unfolding
      double jump kinetic experiments were also performed to monitor the formation of
      native dimer as a function of folding delay times. The data here demonstrate that
      the dimeric intermediate is obligatory and on-pathway. The folding mechanism of
      FIS, when compared to other intertwined, alpha-helical, homodimers, suggests that
      a transient kinetic dimeric intermediate may be a common feature of the folding
      of intertwined, segment-swapped, alpha-helical dimers.

PMID- 14698302
TI  - Mapping of unit boundaries of a protein: exhaustive search for permissive sites
      for duplication by complementation analysis of random fragment libraries of
      tryptophan synthase alpha subunit.
AB  - To identify peptide units that make up a single-domain protein, we searched for
      possible combinations of N and C-fragments that exhibit functional
      complementation, and attempted an exhaustive evaluation of peptide unit
      boundaries. The tryptophan synthase alpha subunit was used as a model enzyme,
      which has a single TIM (beta8/alpha8) barrel domain. Libraries comprising
      randomly digested N and C-fragments were constructed, and clones expressing
      enzymatic activity were selected by the ability to confer growth of the
      Escherichia coli trpA mutant on a medium lacking tryptophan. More than 50 clones
      were obtained, and two cleavable positions were found on the loops after extra
      helix 2' and helix 5. Half of the clones harbored N and C-fragments having an
      overlap between two fragments. The remaining clones harbored one fragment made by
      the fusion of N and C-fragments with insertional sequence duplication. Mapping
      the frequency of occurrence of fragment overlap and insertional duplication
      showed significant peaks at two loops, which coincide with the cleavable sites.
      These results suggest that the boundaries of unit fragments are located at these
      positions, and that bisection, fragment overlap and insertion are all possible at
      the unit boundaries.

PMID- 14698303
TI  - Ligand-dependent dynamics and intramolecular signaling in a PDZ domain.
AB  - Allosteric communication is a fundamental process that proteins use to propagate
      signals from one site to functionally important distal sites. Although allostery
      is usually associated with multimeric proteins and enzymes, "long-range"
      communication may be a fundamental property of proteins. In some cases,
      communication occurs with minimal structural change. PDZ (post-synaptic density
      95/discs large/zonula occludens-1) domains are small, protein-protein binding
      modules that can use multiple surfaces for docking diverse molecules.
      Furthermore, these domains have long-range energetic couplings that link the
      ligand-binding site to distal regions of the structure. Here, we show that
      allosteric behavior in a representative member of the PDZ domain family may be
      directly detected using side-chain methyl dynamics measurements. The changes in
      side-chain dynamics parameters in the second PDZ domain from the human tyrosine
      phosphatase 1E (hPTP1E) were determined upon binding a peptide target. Long-range
      dynamic effects were detected that correspond to previously observed pair-wise
      energetic couplings. These results provide one of the first experimental examples
      for the potential role of ps-ns timescale dynamics in propagating long-range
      signals within a protein, and reinforce the idea that dynamic fluctuations in
      proteins contribute to allosteric signal transduction.

PMID- 14698304
TI  - Role of the lysine-rich cluster of the C2 domain in the phosphatidylserine
      dependent activation of PKCalpha.
AB  - The C2 domain of PKCalpha is a Ca(2+)-dependent membrane-targeting module
      involved in the plasma membrane localization of the enzyme. Recent findings have
      shown an additional area located in the beta3-beta4 strands, named the lysine
      rich cluster, which has been demonstrated to be involved in the PtdIns(4,5)P(2)
      dependent activation of the enzyme. Nevertheless, whether other anionic
      phospholipids can bind to this region and contribute to the regulation of the
      enzyme's function is not clear. To study other possible roles for this cluster,
      we generated double and triple mutants that substituted the lysine by alanine
      residues, and studied their binding and activation properties in a
      Ca(2+)/phosphatidylserine-dependent manner and compared them with the wild-type
      protein. It was found that some of the mutants exerted a constitutive activation
      independently of membrane binding. Furthermore, the constructs were fused to
      green fluorescent protein and were expressed in fibroblast cells. It was shown
      that none of the mutants was able to translocate to the plasma membrane, even in
      saturating conditions of Ca(2+) and diacylglycerol, suggesting that the
      interactions performed by this lysine-rich cluster are a key event in the
      subcellular localization of PKCalpha. Taken together, the results obtained showed
      that these lysine residues might be involved in two functions: one to establish
      an intramolecular interaction that keeps the enzyme in an inactive conformation;
      and the second, once the enzyme has been partially activated, to establish
      further interactions with diacylglycerol and/or acidic phospholipids, leading to
      the full activation of PKCalpha.

PMID- 14698305
TI  - Crystal structure of MshB from Mycobacterium tuberculosis, a deacetylase involved
      in mycothiol biosynthesis.
AB  - All living species require protection against the damaging effects of the
      reactive oxygen species that are a natural by-product of aerobic life. In most
      organisms, glutathione is a critical component of these defences, maintaining a
      reducing environment inside cells. Some bacteria, however, including pathogenic
      mycobacteria, use an alternative low molecular mass thiol compound called
      mycothiol (MSH) for this purpose. Enzymes that synthesize MSH are attractive
      candidates for the design of novel anti-TB drugs because of the importance of MSH
      for mycobacterial life and the absence of such enzymes in humans. We have
      determined the three-dimensional structure of MshB (Rv1170), a metal-dependent
      deacetylase from Mycobacterium tuberculosis that catalyses the second step in MSH
      biosynthesis. The structure, determined at 1.9A resolution by X-ray
      crystallography (R=19.0%, R(free)=21.4%), reveals an alpha/beta fold in which
      helices pack against a seven-stranded mostly parallel beta-sheet. Large loops
      emanating from the C termini of the beta-strands enclose a deep cavity, which is
      the location of the putative active site. At the bottom of this cavity is a metal
      binding site associated with a sequence motif AHPDDE that is invariant in all
      homologues. An adventitiously bound beta-octylglucoside molecule, used in
      crystallization, enables us to model the binding of the true substrate and
      propose a metal-dependent mechanistic model for deacetylation. Sequence
      comparisons indicate that MshB is representative of a wider family of enzymes
      that act on substituted N-acetylglucosamine residues, including a deacetylase
      involved in the biosynthesis of glycosylphosphatidylinositol (GPI) anchors in
      eukaryotes.

PMID- 14698306
TI  - Is surgical science dead? The Excelsior Society lecture.

PMID- 14698307
TI  - Trauma fatalities: time and location of hospital deaths.
AB  - BACKGROUND: Analysis of the epidemiology, temporal distribution, and place of
      traumatic hospital deaths can be a useful tool in identifying areas for research,
      education, and allocation of resources. STUDY DESIGN: Trauma registry-based study
      of all traumatic hospital deaths at a Level I urban trauma center during the
      period 1993 to 2002. The time and hospital location where deaths occurred were
      analyzed according to mechanism of injury, age, Glasgow Coma Score, and body
      areas with severe injury (Abbreviated Injury Scale [AIS] >/= 4). Logistic
      regression analysis was used to identify risk factors associated with death at
      various times after admission. RESULTS: During the study period there were 2,648
      hospital trauma deaths. The most common body area with critical injuries (AIS >/=
      4) was the head (43%), followed by the chest (28%) and the abdomen (19%).
      Overall, 37% of victims had no vital signs present on admission. Chest AIS >/= 4,
      penetrating trauma, and age greater than 60 years were significant risk factors
      associated with no vital signs on admission. Patients with severe chest trauma
      (AIS >/= 4) reaching the hospital alive were significantly more likely to die
      within the first 60 minutes than were patients with severe abdominal or head
      injuries (17% versus 11% versus 7%). In patients reaching the hospital alive, the
      time and place of death varied according to mechanism of injury and injured body
      area. Deaths caused by severe head trauma peaked at 6 to 24 hours, and deaths
      caused by severe chest or abdominal trauma peaked at 1 to 6 hours after
      admission. CONCLUSIONS: The temporal distribution and location of trauma deaths
      are influenced by the mechanism of injury, age, and the injured body area. These
      findings may help in focusing research, education, and resource allocation in a
      more targeted manner to reduce trauma deaths.

PMID- 14698308
TI  - Endogenous immune response to early- and intermediate-stage melanoma is
      correlated with outcomes and is independent of locoregional relapse and standard
      prognostic factors.
AB  - BACKGROUND: Standard prognostic factors, including precise staging of the
      regional lymph nodes, cannot accurately determine which early-stage melanomas
      will metastasize. The immune response to a 90-kd tumor-associated antigen
      correlates with occult nodal disease and survival of patients receiving vaccine
      therapy for melanoma. We hypothesized that this response might have prognostic
      significance independent of standard prognostic features. STUDY DESIGN: Patients
      with primary melanomas 1.01 to 2.00 mm and tumor-negative regional lymph nodes
      were identified. Group 1 comprised 50 patients who died of metastases within 7
      years after complete surgical treatment; group 2 comprised 50 patients who were
      matched with group 1 for six standard prognostic features but who lived at least
      10 years without recurrence. Postoperative sera were analyzed for an immune
      complex to TA90 and for immunoglobulin-G and immunoglobulin-M antibodies against
      TA90. RESULTS: Median thickness of the primary melanoma was 1.40 +/- 0.31 mm and
      1.42 +/- 0.32 mm in groups 1 and 2, respectively; median Clark's level of
      invasion was III in both groups, and 26 patients in each group had ulcerated
      primaries. Median TA90-IC level and rate of TA90-IC positivity (optical density
      greater than 0.410) were 0.557 +/- 0.43 and 82%, respectively, in group 1 and
      0.305 +/- 0.15 and 18%, respectively, in group 2 (p < 0.001). The anti-TA90 IgM
      level was significantly elevated in 12% of group 1 (median titer 1:150) and 62%
      of group 2 (median titer 1:800) (p < 0.001). There was no significant difference
      in anti-TA90 IgG levels between the two groups. CONCLUSIONS: A positive TA90-IC
      level and absence of an anti-TA90 IgM response correlate with distant metastasis
      when melanoma is low risk or intermediate risk by standard prognostic factors.

PMID- 14698309
TI  - Carotid body tumor excisions: adverse outcomes of adding carotid endarterectomy.
AB  - BACKGROUND: Carotid body tumors (CBT) are rare, infrequently malignant vascular
      neoplasms that are near the carotid bifurcation. Surgical excision is the
      treatment of choice, but individual surgeons or an institution cannot accumulate
      sufficient expertise to evaluate their outcomes with confidence. Our purpose was
      to report outcomes of surgical procedures for CBT from a nationwide dataset.
      STUDY DESIGN: Data were retrieved from the Nationwide Inpatient Sample from
      nonfederal hospital discharge abstracts. Data were queried for ICD-9-CM code
      39.8, operations on the carotid body and vascular bodies, and code 38.2, carotid
      endarterectomy. Outcomes analyzed were length of stay, charges, and in-hospital
      mortality. RESULTS: An estmated 4,601 operations were identified, 3,746 for CBT
      surgical procedures only, and in 855 a carotid endarterectomy was also performed.
      Overall morbidity was 3.3%. Mortality with CBT alone was 2.0% but was 8.8% if
      carotid endarterectomy was also performed. CBT surgical procedures are most
      commonly performed in western states where higher elevations are found. Women
      constituted 59% of the population; mortality for women was higher than for men
      (12.4% versus 7.9%). Mortality in urban teaching hospitals was 2.1% and in
      nonteaching hospitals 4.9%. CONCLUSIONS: CBT surgical procedures are rare but are
      performed across a broad age spectrum. Mortality rate is low for patients having
      CBT alone but rises when CE is added. Women are more commonly affected and fare
      less well. Addition of CE to CBT surgical procedures and the resulting poor
      outcomes have not been previously described. Consideration should be given to
      referral of CBT patients to hospitals where mortality rates are low.

PMID- 14698310
TI  - The impact of complications on outcomes after resection for esophageal and
      gastroesophageal junction carcinoma.
AB  - BACKGROUND: Efforts to improve surgical outcomes have traditionally focused on
      improving preoperative patient selection and reducing the risk of postoperative
      medical complications. Strategies to optimize surgical technique have been less
      well studied. We sought to assess the relation between complications related to
      surgical technique and outcomes after esophagogastrectomy for cancer. STUDY
      DESIGN: Medical records of 510 consecutive patients undergoing
      esophagogastrectomy for invasive squamous cell carcinoma or adenocarcinoma at
      Memorial Sloan-Kettering Cancer Center from 1996 to 2001 were reviewed. Data on
      diagnosis, stage of disease, therapies received, surgical approach, patient
      comorbidities, technical complications, and postoperative medical complications
      and outcomes including length of stay and overall survival were determined by one
      reviewer of the medical records. The primary predictor was surgical complications
      and the primary outcome was survival. RESULTS: Of the 150 patients studied 138
      (27%) had complications directly attributable to surgical technique, such as an
      anastomotic leak, a paralyzed vocal cord, or chylothorax. At 3 years 43 of 138
      patients (31%) with technical complications were alive, whereas 179 of 372
      patients (48%) without technical complications were alive. Technical
      complications were associated with increased length of stay (median 23 days
      versus 11 days, p < 0.001), increased in-hospital mortality (12.3% versus 3.8%, p
      < 0.001), and a higher rate of medical complications (77.5% versus 47.3%, p <
      0.001). After controlling for age, medical comorbidities, use of induction
      therapy, tumor stage, histology, and location, and completeness of resection the
      presence of a technical complication was highly predictive of poorer overall
      survival; the multivariable hazard ratio was 1.41 (1.22 to 1.63, p = 0.008).
      CONCLUSIONS: Technical complications have a large negative impact on survival
      after esophagogastrectomy for cancer. Strategies to optimize surgical technique
      and minimize complications should improve outcomes in this cancer operation.

PMID- 14698311
TI  - Risk factors for liver metastases after curative surgical procedures for gastric
      cancer: a prospective study of 208 patients treated with surgical resection.
AB  - BACKGROUND: The aim of this study was to evaluate the risk of liver metastases
      after radical surgical treatment for gastric cancer, the potential risk factors
      involved, and the sensitivity of serum tumor markers during followup. STUDY
      DESIGN: A total of 208 patients who had undergone curative resection for primary
      gastric cancer and a prospective followup protocol were studied. The association
      between clinicopathologic variables and hepatic recurrence was investigated using
      standard univariate methods and multivariate Cox regression analysis. RESULTS:
      Mean followup time (+/- SD) for the entire patient population was 51 +/- 38
      months (median 52 months) and was 88 +/- 24 months (median 81 months) for disease
      free patients. Recurrence of gastric cancer was documented in 109 of 208 patients
      (52.4%). Liver metastases were found in 28 of 208 patients (13.5%); in most of
      these patients (82.1%) diagnosis was made within 2 years after surgical
      treatment. The estimated cumulative risk of liver metastases after 5 years was
      16.4%. Cox regression analysis identified lymph node involvement (adjusted
      relative risk [RR] = 6.28, 95% confidence interval [CI] = 2.11 to 18.70, p =
      0.001), preoperative positivity for CEA, CA 19-9, or CA 72-4 (RR = 5.18, 95% CI =
      1.75 to 15.37, p = 0.003), and intestinal histotype (RR = 3.08, 95% CI = 1.06 to
      8.96, p = 0.039) as independent predictors of hepatic recurrence. In 27 of 28
      cases hepatic recurrence was associated with an increase in CEA, CA 19-9, or CA
      72-4 serum levels above the cutoff, either before or at the time of the clinical
      diagnosis (sensitivity 96.4%). CONCLUSIONS: Preoperative positivity for serum
      tumor markers, lymph node involvement, and intestinal histotype are risk factors
      for liver metastases after radical surgical treatment for gastric cancer.
      Postoperative measurement of serum tumor markers may be useful for an early
      diagnosis of hepatic recurrence during followup.

PMID- 14698312
TI  - Intraoperative identification and neurophysiologic parameters to verify pelvic
      autonomic nerve function during total mesorectal excision for rectal cancer.
AB  - BACKGROUND: Preservation of parasympathetic and sympathetic nerves is required to
      avoid urogenital function disturbances after total mesorectal excision (TME) for
      rectal carcinoma. This study sought to determine whether intraoperative
      stimulation of parasympathetic nerves with monitoring of bladder contraction is
      useful in meeting this demand. STUDY DESIGN: In a prospective pilot study, 17
      patients, 11 men and 6 women, underwent TME with pelvic autonomic nerve
      preservation performed by an experienced surgeon. The parasympathetic nerves were
      stimulated by an electrostimulation device (Screener 3625, Medronic), and the
      resulting bladder contraction was measured manometrically in all patients.
      Variations in pulse rate and voltage were measured to determine optimal
      stimulation parameters. A standardized questionnaire was used to record
      urogenital function disturbances. Residual urine volume was measured by
      ultrasound pre- and postoperatively. Shortterm outcomes data were evaluated to
      establish a possible association between intraoperative test results and
      postoperative bladder function. RESULTS: In 15 of 17 patients undergoing TME with
      pelvic autonomic nerve preservation for rectal carcinoma, the parasympathetic
      nerves were identified based on nerve stimulation-induced bladder contraction.
      Two patients with negative results on intraoperative nerve stimulation had
      persisting bladder dysfunction requiring an indwelling catheter after discharge
      from hospital. In spite of a short median followup of 2 months (range 1 to 4
      months), in 7 of 10 men with intact erectile function prior to surgery,
      postoperative erectile dysfunction could be excluded. The study showed a pulse
      rate of 35 Hz and an electric potential of 12 V to be optimal stimulation
      parameters, associated with a mean intravesical pressure rise of 12.7 cm H(2)O
      (range 2.8 to 18.0 cm H(2)O). CONCLUSIONS: Intraoperative nerve stimulation with
      monitoring of intravesical pressure represents a technically simple procedure for
      the identification and verification of function of pelvic parasympathetic nerves
      during TME for rectal carcinoma.

PMID- 14698313
TI  - Protection against concanavalin A-induced hepatocyte apoptosis by molsidomine is
      time-dependent.
AB  - BACKGROUND: Viral hepatitis and autoimmune liver diseases cause hepatocyte
      apoptosis. Concanavalin A (Con A)-induced hepatitis resembles human viral
      hepatitis and autoimmune hepatitis. The role of nitric oxide (NO) in liver injury
      was controversial in different liver injury models. We hypothesize both
      endogenous and exogenous NO protect liver against Con A-induced liver injury.
      Molsidomine is metabolized into SIN-1 by the liver, and SIN-1 subsequently
      generates NO. So, molsidomine was used as a NO donor in this study. STUDY DESIGN:
      To study a protective role of endogenous NO in Con A-induced liver injury, mice
      were pretreated with a specific inducible nitric oxide synthase (iNOS) inhibitor,
      L-N(6)-(1-iminoethyl)-lysine (L-NIL), before Con A challenge. To study a time
      dependent protection against Con A-induced liver injury, animals were either
      given molsidomine, a NO donor, before or after Con A administration. Serum
      alanine aminotranferase (ALT) was analyzed. Liver samples were subjected to DNA
      fragmentation assay, terminal deoxynucleotidyl transferase-mediated dUTP-biotin
      nick end labeling stain, Western blot analysis, and caspase activity assays.
      RESULTS: Animals pretreated with L-NIL had significantly increased serum ALT
      levels compared with those challenged with Con A alone; but pretreatment with
      molsidomine dramatically decreased ALT levels in L-NIL-pretreated animals or in
      animals that received Con A alone. Administration of molsidomine 30 minutes
      before or 1, 2, and 3 hours after Con A injection significantly reduced serum ALT
      levels and attenuated hepatocyte apoptosis from caspase inactivation. The ALT
      reduction was associated with inhibition of both caspase-3 and caspase-8
      activation and reduction of hepatocyte apoptosis. CONCLUSIONS: Endogenous NO
      plays an important protective role against Con A-induced liver injury by reducing
      hepatocyte apoptosis. Administration of a NO donor early after Con A injection
      protects the liver from injury. This is the first study demonstrating a time
      dependent inhibition of liver injury induced by Con A administration.

PMID- 14698314
TI  - Iatrogenic bladder perforations: longterm followup of 65 patients.
AB  - BACKGROUND: We reviewed our experience with bladder perforations to better
      understand the causes of these injuries and to describe their management and its
      effect on longterm outcomes. STUDY DESIGN: Our bladder trauma database yielded 65
      patients during a 12-year period, followed for a mean of 36 months, who had
      sustained iatrogenic bladder perforations. Endourologic procedures were excluded.
      Demographic data, surgical details, mechanism of injury, anatomic location,
      grading, diagnosis, management, and outcomes were assessed. RESULTS: Gynecologic
      procedures accounted for 40 perforations (61.5%), general surgical procedures for
      17 (26.2%), and urologic procedures for 8 (12.3%). The type of gynecologic
      surgery included abdominal hysterectomy in 16 (40%), resection of a pelvic mass
      in 12 (30%), cesarean section in 10 (25%), and diagnostic laparoscopy in 2 (5%).
      Of the general surgical procedures, eight were for colon cancer (47.1%), six for
      diverticulitis (35.3%), and three for inflammatory bowel disease (17.6%); of the
      urologic injuries, six occurred during vaginal surgery and two during
      laparoscopy. Predisposing factors were identified in 52 patients (80%).
      Intraoperative urologic consultation was obtained in 63 of 65 patients, with
      prompt identification and repair. In two cases a concurrent left ureteral injury
      was identified and managed by reimplantation. The sole complication was a
      vesicovaginal fistula 2 months postoperatively, so the success rate for repair
      was 98.4%. CONCLUSIONS: Although infrequent, iatrogenic bladder perforations can
      occur during any pelvic, abdominal, or vaginal procedure. Prompt intraoperative
      recognition is paramount to ensure satisfactory outcomes. Adequate repair usually
      can be achieved simply by vesicorrhaphy, limiting unnecessary extravesical
      dissection. With this approach, morbidity can be minimized.

PMID- 14698315
TI  - Prognostic significance of p53, bcl-2, and Bax expression in early breast cancer.
AB  - BACKGROUND: The use of adjuvant chemotherapy in early breast carcinoma is
      controversial, with most advocating its use in high-risk patients as defined by
      specific clinicopathologic parameters. Both bcl-2 and p53, which play a role in
      determining tumor growth by their effects on apoptosis and cell proliferation
      respectively, may serve to delineate this subset more accurately. The purpose of
      this study was to determine the prognostic value of bcl-2, Bax, and mutant p53 in
      stage I breast cancer. STUDY DESIGN: A total of 75 patients with stage Ic breast
      carcinoma diagnosed from 1989 to 1992 were identified retrospectively and
      clinicopathologic parameters such as age, tumor size, estrogen receptor (ER) and
      progesterone receptor (PR) status, disease-free survival and overall survival
      obtained. Paraffin-embedded formalin-fixed tissues were immunostained with bcl-2,
      Bax and p53 monoclonal antibodies using a standard avidin biotin peroxidase
      reaction. Stained slides were evaluated by two independent pathologists for
      staining intensity and percentage of cells staining positively. Cox regression
      was used for multivariate survival analysis using the clinicopathologic
      parameters and molecular markers. Chi-square tests were used for frequency
      tables. RESULTS: Mean patient age was 58 years (range 29 to 79 years) with a
      median followup of 80 months from time of diagnosis. The most common
      histopathology was infiltrating ductal carcinoma. Neither bcl-2 nor Bax
      expression was associated statistically with disease-free or overall survival.
      Expression of mutant p53 was associated with a significant decrease in both 5
      year disease-free survival (70% versus 98%, p </= 0.01 in multivariate analysis)
      and 5-year overall survival (74% versus 100%, p = 0.03). Expression of bcl-2 was
      associated with hormone receptor expression and tumor diploid status. Of tumors
      expressing bcl-2, 36 of 49 (73%) were ER+ (p = 0.017, versus tumors not
      expressing bcl-2, 6 of 15 [40%]), 22 of 49 (45%) PR+ (p = 0.027 versus tumors not
      expressing bcl-2, 2 of 15 [13%]) and 28 of 44 (64%) diploid (p = 0.004 versus
      tumors not expressing bcl-2, 1 of 9 [11%]). CONCLUSIONS: These results indicate
      that bcl-2 expression is significantly associated with hormonal receptor status
      and that p53 is a significant prognostic marker for survival in early breast
      cancer.

PMID- 14698316
TI  - What's new in colon and rectal surgery.

PMID- 14698317
TI  - Relationship between objective assessment of technical skills and subjective in
      training evaluations in surgical residents.
AB  - BACKGROUND: Technical skills of residents have traditionally been evaluated using
      subjective In-Training Evaluation Reports (ITERs). We have developed the McGill
      Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS), an
      objective measure of laparoscopic technical ability. The purpose of the study was
      to assess the concurrent validity of the MISTELS by exploring the relationship
      between MISTELS score and ITER assessment. STUDY DESIGN: Fifty surgery residents
      were assessed on the MISTELS system. Concurrent ITER assessments of technical
      skill were collected, and the proportion of superior ratings for the year was
      calculated. Statistical comparisons were performed by ANOVA and chi-square
      analysis. The Pearson correlation coefficient was used to compare the scores in
      the MISTELS with the ITER ratings. RESULTS: The 50 residents received 277 ITERs
      for the year, of which 103 (37%) were "superior," 170 (61%) "satisfactory," 4
      (1%) "borderline," and 0 "unsatisfactory." The MISTELS score correlated
      moderately well with the proportion of superior ITER scores (r = 0.51, p < 0.01).
      Residents who passed the MISTELS had a higher proportion of superior ITER
      assessments than those who failed the MISTELS (p = 0.02), but residents who
      performed below their expected level on the MISTELS still received mainly
      satisfactory ITERs (82 +/- 18%). CONCLUSIONS: The ITER assessment is poor at
      identifying residents with below-average technical skills. Residents who perform
      well in the MISTELS laparoscopic simulator also have better ITER evaluations,
      providing evidence for the concurrent validity of the MISTELS. Multiple
      assessment instruments are recommended for assessment of technical competency.

PMID- 14698318
TI  - Surgeon workhours in the era of limited resident workhours.
AB  - BACKGROUND: Resident workhours have received much attention, yet there is little
      information concerning faculty workhours. In addition, the perspectives of
      surgical faculty on the anticipated effects of reducing resident hours have not
      been studied. STUDY DESIGN: An anonymous survey was distributed to all clinical
      faculty in the Departments of Surgery, Neurosurgery, Orthopaedics, and
      Otolaryngology at a single, large academic institution. Surgeons completed a
      detailed retrospective report of hours worked during a 1-week period. Opinions
      regarding resident workhour restrictions were also elicited. Chi-square or
      Student's t-tests were used to determine p values as appropriate, with p </= 0.05
      considered significant. RESULTS: Of 120 surveys distributed, 102 (85%) were
      returned. Subspecialty departments comprised 51% of respondents with 49% from
      general surgeons. The mean number of hours worked per week by faculty was 70.4 +/
      12.5 (SD) (73.8 +/- 14.1 for general surgeons versus 67.1 +/- 9.9 for
      subspecialists, p = 0.006), with only 44.1% having at least 1 day per week free
      from clinical duties. Up to 95% of general surgeons are paged overnight at least
      once per week (mean 13.6 +/- 11.2 calls/week), with 73% returning from home at
      least once during the week (mean 1.8 +/- 1.1 returns/week). Importantly, 84% of
      general surgeons believe reducing resident workhours will increase faculty hours,
      compared with 57% of subspecialists (p = 0.004). In addition, 87% predict that
      reducing resident hours will compromise surgical education, with only 11%
      believing the benefits of hour reduction will outweigh the negatives.
      CONCLUSIONS: The recommended limit for resident workhours closely approximates
      the average number of hours worked by surgical faculty in an academic center.
      Despite this, significant concern exists among the majority of surgical faculty
      regarding the impact of resident workhour restriction, both on faculty workhours
      and on resident education.

PMID- 14698320
TI  - Gastrointestinal injury secondary to extracorporeal shock wave lithotripsy: a
      review of the literature since its inception.

PMID- 14698321
TI  - Current management of esophageal leiomyoma.

PMID- 14698322
TI  - An evolving strategy for surgical care.

PMID- 14698323
TI  - Esophagopericardial fistula in a partially excluded esophagus.

PMID- 14698324
TI  - Symptomatic persistent sciatic artery.

PMID- 14698325
TI  - A technique of enteroenterostomy to prevent alimentary limb obstruction in
      laparoscopic Roux-en-Y gastric bypass.

PMID- 14698326
TI  - Trocar placement for laparoscopic abdominal procedures: a simple standardized
      method.

PMID- 14698327
TI  - Multiple gastric carcinoids.

PMID- 14698328
TI  - Incisional hernia and small bowel obstruction.

PMID- 14698330
TI  - Churchill's inguinal hernia repair.

PMID- 14698332
TI  - Nuchal translucence incorporated into a one-stage multifactorial screening model
      for Down syndrome prediction at second-trimester pregnancy.
AB  - The aim of this study was to achieve one-stage screening for trisomy 21 using a
      combination of nuchal translucency (NuT) measurement and maternal serum alpha
      fetoprotein (AFP) and free beta-human chorionic gonadotrophin (hCG) biochemistry
      levels in the second trimester among a high-risk study population. From January
      1998 to June 2001, 45 cases of trisomy 21 were prenatally found and confirmed in
      the hospital-based cytogenetic diagnosis laboratory. A total of 867 normal
      singleton pregnancies were enrolled as controls from the antenatal care clinics
      in the hospital. All study and control subjects between 13 weeks and 18 weeks of
      gestation with a mean age of 15.2 +/- 1.3 weeks underwent one-stage nuchal
      translucence measurements and maternal serum biochemical screening for Down
      syndrome. The final logistic model contained beta-hCG (multiples of the
      gestational median or MoM), maternal age (matA), nuchal translucence (NuT MoM)
      and AFP (MoM) as covariates. Also, the estimated coefficients of the regression
      were highly significant. This model provided the estimated probability of Down
      syndrome as follows: Pr (Down syndrome) = exp (Z)/ [1 + exp (Z)], where Z = 
      11.18 + 0.64 x (beta-hCG MoM) + 0.25 x matA + 1.32 x NuT MoM -2.23 x AFP MoM. The
      logistic regression with estimated coefficients was installed in a Palm digital
      assistant (PDA) equipped with Excel (Microsoft). The risk probability of Down
      syndrome could be readily calculated after inputting data for all four predictor
      variables.

PMID- 14698333
TI  - Prenatal assessment of normal fetal humerus volume by three-dimensional
      ultrasound.
AB  - Because fetal humerus dysplasia is associated with a variety of congenital
      syndromes, prenatal assessment of the fetal humerus growth is very important. The
      fetal humerus volume is one of the indexes in evaluating the humerus growth, but
      it has never been studied by 3-D ultrasound (US) in utero. To establish a normal
      reference chart of the fetal humerus volume for clinical use, we undertook a
      prospective and cross-sectional study using 3-D US to assess the fetal humerus
      volume in normal pregnancy. A total of 216 singleton fetuses that ranged between
      20 and 40 weeks of gestation and fit the criteria of normal pregnancies were
      included in this study. Our results showed that the fetal humerus volume is
      highly correlated with the gestational age (GA). Using GA as the independent
      variable and the humerus volume as the dependent variable, the best-fit
      regression equation was humerus volume (mL) = 0.0044GA(2) - 0.0841GA + 0.6874 (r
      = 0.97, n = 216, p < 0.0001). For clinical use, a chart of normal growth centiles
      of the fetal humerus volume was then established based on this equation. In
      addition, the common indexes of fetal biometry, such as biparietal diameter,
      occipitofrontal diameter, head circumference, abdominal circumference, femur
      length and estimated fetal weight, were all highly correlated with the humerus
      volume (all p < 0.0001). In conclusion, our data of the fetal humerus volume
      assessed by 3-D US can serve as a useful reference in evaluating the fetal
      humerus growth during normal gestation.

PMID- 14698334
TI  - Accuracy of three-dimensional transvaginal ultrasound in uterus volume
      measurements; comparison with two-dimensional ultrasound.
AB  - The purpose of this study was to document the accuracy of 3-D uterus volume and
      to compare it with 2-D measurements. Transvaginal ultrasound (US) examinations
      were performed in 48 consecutive patients before hysterectomy. The examinations
      were stored digitally on an internal disk drive for subsequent measurements in
      virtual organ computer-aided analysis (VOCAL) program. Immediately after the
      hysterectomy, the true volume was measured in a water bath. A total of 5 patients
      were excluded due to difficulty of identifying the borders of their uterus; 8
      patients were excluded because of too large fibroids or diffuse hypertrophic
      enlargement of uterus (volume > 220 mL). Although the volumes estimated by the 3
      D method were not significantly different (p = 0.126 first measurement, p = 0.561
      second measurement), the volumes estimated by the 2-D method were significantly
      different (p = 0.005 first measurement, p = 0.012 second measurement). The mean
      error rates of the two 3-D volume measurements by the same observer were 7.4% and
      7.9%, and they were 22.2% and 21.0% for the 2-D volume measurements. It may be
      concluded that the volume of the uterus can be measured more accurately by 3-D US
      than by 2-D US.

PMID- 14698335
TI  - The interobserver reliability of ovarian volume measurement is improved with
      three-dimensional ultrasound, but dependent upon technique.
AB  - The effect of measurement technique on the interobserver reliability of ovarian
      volume calculation from three-dimensional (3-D) ultrasound (US) data was
      investigated. Ovarian volume was calculated in 20 patients by two observers using
      both the "prolate ellipsoid formula" and a new 3-D rotational technique (VOCAL).
      There was a significant difference between observers in mean ovarian volume
      calculated by the prolate ellipsoid formula (31.54 mL vs. 26.54 mL: p < 0.05),
      which proved to be a significantly less reliable technique than 3-D rotational
      volume calculation with VOCAL. Image quality was significantly better (p < 0.001)
      and measurements were significantly more reliable (p < 0.05) in the B-plane than
      in the C- plane of the multiplanar display. Rotational measurement of ovarian
      volume from 3-D US data is significantly more reliable between observers than
      volume estimation from 2-D parameters using the prolate ellipsoid formula, but is
      dependent upon image quality, which is significantly better in the B-plane than
      in the C-plane.

PMID- 14698336
TI  - Quantitative ultrasound at the hand phalanges in women on hormone replacement
      therapy.
AB  - The aim of the observational study was to evaluate the influence of hormone
      replacement therapy (HRT) on the results of quantitative ultrasound (US) at the
      hand phalanges in 732 women (mean age about 53 years). Among them were 228
      postmenopausal women treated within 6 months after the last menstrual bleeding
      (group 1), 90 postmenopausal women taking HRT after a break between menopause and
      the onset of the therapy of about 2 years (group 2) and 414 controls. Mean age
      and body size did not differ significantly between groups studied. Years since
      menopause (YSM) did not differ significantly between group 2 and controls.
      Skeletal status was assessed using DBM Sonic 1200 (IGEA, Carpi, Italy), which
      measures amplitude-dependent speed of sound (Ad-SoS) in m/s. Ad-SoS was
      significantly higher in both groups on HRT than in controls (p < 0.000001), and
      in group 1 compared with group 2 (p < 0.05). The duration of HRT did not affect
      Ad-SoS values. The influence of age on Ad-SoS values was significantly weaker in
      women on HRT than in controls and YSM did not influence Ad-SoS value in
      postmenopausal women taking HRT. In controls, YSM negatively and significantly
      affected Ad-SoS value. In conclusion, HRT administered in perimenopause or early
      postmenopause had a significant influence on quantitative US measurements at the
      hand phalanges, and the difference between both treated groups suggests that HRT
      ought to be indicated directly after the last menstrual bleeding.

PMID- 14698337
TI  - Validation of ultrasound contrast destruction imaging for flow quantification.
AB  - Our purpose was to validate in vitro a kinetic flow model based on microbubble
      signal decay curve. Using a 3.5 MHz transducer and phase-inversion (1.8 MHz
      central transmit frequency), a renal dialysis cartridge oriented vertically was
      imaged in the transverse plane as 1:1000 dilution of AF0150 was infused at 50,
      100, 200, 300 and 400 mL/min. Ten gray-scale images were acquired at each
      infusion rate using 2.5, 5 and 10 frames/s at 100%, 40%, 15% or 1% of maximum
      transmit power. Video-intensity measured on each 10 images was fit to a kinetic
      model using Sigma Plot that yielded microbubble concentration, velocity and
      destruction per frame. These were correlated with the experimental conditions. At
      100% power, video-intensity on the first frame (microbubble concentration at
      equilibrium) was similar for all flow and frame rates. The model fit the
      experimental data for all flows at 10 frames/s and for flows lower than 400 and
      100 mL/min at 5 frames/s and 2.5 frames/s, respectively. The calculated flow was
      similar to the experimental flow rates, regardless of technique (r(2) = 0.98).
      Microbubble fraction destroyed per frame was similar for all flow and frame rates
      and increased linearly with transmit power (r(2) > 0.98). These results suggest
      that using appropriate power and frame rate for a given flow rate, estimates of
      fractional blood volume, flow and destruction fraction can be calculated from the
      decay curve using 10 frames that can be acquired in 1 to 4 s.

PMID- 14698338
TI  - Transient elastography: a new noninvasive method for assessment of hepatic
      fibrosis.
AB  - Chronic hepatitis is accompanied by progressive deposit of hepatic fibrosis,
      which may lead to cirrhosis. Evaluation of liver fibrosis is, thus, of great
      clinical interest and, up to now, has been assessed with liver biopsy. This work
      aims to evaluate a new noninvasive device to quantify liver fibrosis: the shear
      elasticity probe or fibroscan. This device is based on one-dimensional (1-D)
      transient elastography, a technique that uses both ultrasound (US) (5 MHz) and
      low-frequency (50 Hz) elastic waves, whose propagation velocity is directly
      related to elasticity. The intra- and interoperator reproducibility of the
      technique, as well as its ability to quantify liver fibrosis, were evaluated in
      106 patients with chronic hepatitis C. Liver elasticity measurements were
      reproducible (standardized coefficient of variation: 3%), operator-independent
      and well correlated (partial correlation coefficient = 0.71, p < < 0.0001) to
      fibrosis grade (METAVIR). The areas under the receiver operating characteristic
      (ROC) curves were 0.88 and 0.99 for the diagnosis of patients with significant
      fibrosis (>/= F2) and with cirrhosis ( = F4), respectively. The Fibroscan is a
      noninvasive, painless, rapid and objective method to quantify liver fibrosis.

PMID- 14698339
TI  - Shear-wave generation using acoustic radiation force: in vivo and ex vivo
      results.
AB  - Acoustic radiation force impulse (ARFI) imaging involves the mechanical
      excitation of tissue using localized, impulsive radiation force. This results in
      shear-wave propagation away from the region of excitation. Using a single
      diagnostic transducer on a modified commercial ultrasound (US) scanner with
      conventional beam-forming architecture, repeated excitations with multiple look
      directions facilitate imaging shear-wave propagation. Direct inversion methods
      are then applied to estimate the associated Young's modulus. Shear-wave images
      are generated in tissue-mimicking phantoms, ex vivo human breast tissue and in
      vivo in the human abdomen. Mean Young's modulus values of between 3.8 and 5.6
      kPa, 11.7 kPa and 14.0 kPa were estimated for fat, fibroadenoma and skin,
      respectively. Reasonable agreement is demonstrated between structures in matched
      B-mode and reconstructed modulus images. Although the relatively small magnitude
      of the displacement data presents some challenges, the reconstructions suggest
      the clinical feasibility of radiation force induced shear-wave imaging.

PMID- 14698340
TI  - In vitro evaluation of ultrasound Doppler strain rate imaging: modification for
      measurement in a slowly moving tissue phantom.
AB  - Doppler strain rate imaging (SRI) was evaluated in vitro using a silicone strip
      phantom mimicking slowly moving tissue. A test apparatus was developed that
      enabled controlled strain experiments with variable strain and strain rate to be
      performed. SRI strain was measured at eight different calculated strains (range
      5.7 to 63.4 %) at three different pump speeds with tissue velocity 0.1, 0.5 and
      1.0 mm/s. The effect of varying tissue velocity and strain sample size on the
      measured SRI strain was elaborated. SRI strains agreed well with calculated
      values for strain when SRI strain was measured as the average over the whole
      strip cross-section and the strain sample size was 1.9 mm (mean difference =
      2.78%, limits of agreement +/- 9.97% for tissue velocity 1.0 mm/s, n = 8). The
      variance was substantial if single central samples were used, especially for
      strain sample size of 0.8 mm (mean difference = -7.47%, limits of agreement +/-
      20.90 for tissue velocity 0.5 mm/s, n = 24). Increasing the strain sample size to
      1.9 mm removed some of the underestimation (giving mean difference of -4.46%, n =
      24). We found low intra- and interobserver variation. This study indicates that,
      for the SRI method to give accurate estimates of strain, strain sample size
      should be in the region of 2 mm. Averaging over several ultrasound (US) beams
      increased the accuracy further.

PMID- 14698341
TI  - Visualisation of 4-D colour and power Doppler data.
AB  - Mechanically scanned, cardiac-gated, 4-D colour Doppler and power Doppler data
      were acquired and rendered using multiplanar slice display, surface-fitting (S-F)
      and direct volume rendering (DVR), with interactive viewpoint control or tool
      command language (Tcl)-scripted generation of animation sequences across the
      cardiac cycle. S-F applied the marching cubes algorithm within a YCbCr colour
      space to extract time-varying Doppler regions; supplementally generated surfaces
      enclosed all regions across the full cardiac cycle, partially to alleviate the
      problem of incomplete vessel filling. DVR used integrated intensity, maximum
      intensity and front-to-back projection; the latter applied an opacity function to
      the Cb, Cr and Y colour channels to control the appearance of the blood flow
      signal relative to the background B-mode image. Our most detailed display was a
      hybrid approach that combined multiplanar slicing and DVR.

PMID- 14698343
TI  - Targeted tissue transfection with ultrasound destruction of plasmid-bearing
      cationic microbubbles.
AB  - The aim of this study was to assess the relative efficacy and mechanism of gene
      transfection by ultrasound (US) destruction of plasmid-bearing microbubbles.
      Luciferase reporter plasmid was charge-coupled to cationic lipid microbubbles.
      Rat hindlimb skeletal muscle was exposed to intermittent high-power US during
      dose-adjusted intra-arterial (IA) or IV administration of plasmid-bearing
      microbubbles via the carotid artery or jugular vein, respectively. At 4 days,
      luciferase activity in US-exposed skeletal muscle was 200-fold greater with IA
      than with IV administration of plasmid-bearing microbubbles, and was similar to
      transfection achieved by IM injection of plasmid (positive control). No
      transfection occurred with US and IA injection of plasmid alone. Intravital
      microscopy of the cremaster muscle in mice following administration of
      microbubbles and US exposure demonstrated perivascular deposition of fluorescent
      plasmid, the extent of which was twofold greater for IA compared to IV injection.
      Electron microscopy demonstrated a greater extent of myocellular microporations
      in US-exposed muscle after IA injection of microbubbles. We conclude that muscle
      transfection by US destruction of plasmid-bearing cationic microbubbles is
      amplified by IA, rather than IV, injection of microbubbles due to greater
      extravascular deposition of plasmid and to greater extent of myocellular
      microporation.

PMID- 14698342
TI  - A Newtonian rheological model for the interface of microbubble contrast agents.
AB  - A quantitative model of the dynamics of an encapsulated microbubble contrast
      agent will be a valuable tool in contrast ultrasound (US). Such a model must have
      predictive ability for widely varying frequencies and pressure amplitudes. We
      have developed a new model for contrast agents, and successfully investigated its
      applicability for a wide range of operating parameters. The encapsulation is
      modeled as a complex interface of an infinitesimal thickness. A Newtonian
      rheology with surface viscosities and interfacial tension is assumed for the
      interface, and a modified Rayleigh-Plesset equation is derived. The rheological
      parameters (surface tension and surface dilatational viscosity) for a number of
      contrast agents (Albunex, Optison and Quantison) are determined by matching the
      linearized model dynamics with experimentally obtained attenuation data. The
      model behavior for Optison (surface tension 0.9 N/m and surface dilatational
      viscosity 0.08 msP) was investigated in detail. Specifically, we have carried out
      a detailed interrogation of the model, fitted in the linear regime, for its
      nonlinear prediction. In contrast to existing models, the new model is found to
      capture the characteristic subharmonic emission of Optison observed by. A
      detailed parametric study of the bubble behavior was executed using the ratio of
      scattering to attenuation (STAR). It shows that the encapsulation drastically
      reduces the influence of resonance frequency on scattering cross-section,
      suggesting possible means of improvement in imaging at off-resonant frequencies.
      The predictive capability of the present model indicates that it can be used for
      characterizing different agents and designing new ones.

PMID- 14698344
TI  - Cell detachment method using shock-wave-induced cavitation.
AB  - The detachment of adherent HeLa cells from a substrate after the interaction with
      a shock wave is analyzed. Cavitation bubbles are formed in the trailing, negative
      pressure cycle following the shock front. We find that the regions of cell
      detachment are strongly correlated with spatial presence of cavitation bubbles.
      It is shown that the cavitation bubble collapse generates a transient high-speed
      flow along the substrate surface leading to rapid detachment of the cells. Flow
      trajectories are reconstructed from the video recordings using robust image
      processing methods. From these trajectories, an estimate of the shear stress
      acting on the cells is obtained and the area of detachment is estimated with a
      kinetic model. Furthermore, it is suggested that the application of shock waves
      extends the known methods of cell detachment with the ability to control the
      process in space and time.

PMID- 14698345
TI  - Effect of trabecular orientation on mechanical resistance and ultrasound
      propagation in specimens of equine vertebrae.
AB  - Osteoporosis involves alterations, not only in density, but also in the
      architectural organisation of the bone; in particular, trabecular orientation,
      following the skeletal load directions, lends a high degree of stiffness to the
      whole bone. We investigated the relationship between trabecular orientation,
      density, stiffness and ultrasound (US) propagation in two orthogonal directions
      (par. = parallel to, and ort. = orthogonal to the main orientation of the
      trabeculae) in cylindrical equine bone specimens (thoracic vertebrae) where a
      preferential orientation is present. A total of 15 cylinders were progressively
      decalcified with 0.2 mol/L ethylenediaminetetraacetic acid (EDTA). At different
      levels of decalcification, we measured the apparent density (g/cm(3)), bone
      mineral density or BMD (g/cm(2)), stiffness coefficient (MPa) and various US
      parameters. Before decalcification, stiffness values were the same in all
      directions. As the decalcification proceeded, the stiffness declined and, at low
      BMD values, it was significantly different in the two directions, being the
      highest in the par. one. Different behaviours of US parameters were observed in
      the two directions: SoS (speed of sound) was closely related to apparent density,
      BMD and stiffness in the par. direction (r = 0.88, 0.92 and 0.88, respectively, p
      < 0.0001). In the ort. direction, no significant association has been found
      between SoS and apparent density, BMD or stiffness. In the same experimental
      setup, US fast wave amplitude (FWA) was related to apparent density and BMD in
      the par. direction (r = 0.72 and 0.67, respectively, p < 0.0001) and in the ort.
      direction (r = 0.83 and r = 0.84 respectively, p < 0.0001). FWA was also
      correlated to stiffness in both directions (r = 0.61 par.; 0.81 ort., p <
      0.0001). These results show that trabecular orientation strongly influences both
      mechanical properties of bone and US propagation. Furthermore, we found that US
      parameters can be predictors of mechanical properties of the bone independent of
      bone density.

PMID- 14698346
TI  - On the ultrasonic properties of tendon.
AB  - The strong dependence of tendon echogenicity on insonation angle is explored by
      analyzing echo spectra. Combining echo spectra with high-resolution images from
      several modalities reveals that fluid spaces surrounding fascicles and bundles
      are likely sources of ultrasonic scatter. Mathematical models of tendon structure
      are proposed to explain how the anisotropic microstructure of tendon gives rise
      to angle-dependent echogenicity. Echo spectra from spontaneously damaged equine
      tendon samples were compared with normal equine tendon and found to exhibit a
      dramatic decrease in anisotropic properties that appears to be related to the
      spatial organization and type of collagen generated during repair. Variation in
      echo spectra with insonation angle is a robust indicator of mechanical damage.

PMID- 14698348
TI  - Spatial-temporal display of colour-flow ultrasound for the assessment of the
      effects of intermittent pneumatic compression in limbs.
AB  - Colour-flow M-mode ultrasonography in three dimensions (two spatial, one
      temporal) was used to assess the effects of intermittent pneumatic compression on
      the blood flow velocities in the common femoral vein and artery. The linear array
      of a standard 3-D system was held in place over the vessels, to record while a
      calf and thigh cuff compressed to 60 mmHg. The data was reconstructed in 3-D and,
      subsequently, sliced in different planes. The technique effectively demonstrated
      the emptying of distal veins during compression, and hyperaemia in the artery on
      deflation, in the coronal and sagittal planes. Reconstructions of this type may
      be of use in visualising the distribution of flow changes within blood vessels.

PMID- 14698347
TI  - Ultrasound-mediated release of iron from ferritin.
AB  - We investigated the release of iron from ferritin in aqueous solutions exposed to
      high-frequency ultrasound (US). Our data suggests that superoxide produced as a
      result of ultrasonic cavitation acts as a reducing agent, enabling the release of
      iron from ferritin. We also found that the release of ferritin iron during US
      exposure is enhanced by the addition of 5-hydroxy-1,4-naphthoquinone. We
      hypothesize that this quinone is ultrasonically transformed into a semiquinone
      radical capable of directly and indirectly reducing Fe(3+) in ferritin to soluble
      Fe(2+). Our proposed mechanism for the release of iron from ferritin adds new
      insight to the synergistic effect of quinone-containing cancer drugs with US.

PMID- 14698351
TI  - Fos-like immunoreactive neurons following electrical stimulation of the dorsal
      periaqueductal gray at freezing and escape thresholds.
AB  - Electrical stimulation of the dorsal regions of the periaqueductal gray (PAG)
      leads to defensive reactions characterized as freezing and escape responses.
      Until recently it was thought that this freezing behavior could be due to the
      recruitment of neural circuits in the ventrolateral periaqueductal gray (vlPAG),
      while escape would be mediated by other pathways. Nowadays, this view has been
      changing mainly because of evidence that freezing and escape behaviors thus
      elicited are not altered after lesions of the vlPAG. It has been suggested that
      there are at least two pathways for periaqueductal gray-mediated defensive
      responses, one involving the hypothalamus and the cuneiform nucleus (CnF) which
      mediates responses to immediate danger and another one involving the amygdala and
      vlPAG which mediates cue-elicited responses, either learned or innate. To examine
      this issue further we measured Fos protein expression in brain areas activated by
      electrical stimulation of the dorsolateral PAG (dlPAG) at the freezing and escape
      thresholds. The data obtained showed that freezing-provoking stimulation caused
      increases in Fos expression in the dorsomedial PAG (dmPAG), while escape
      provoking stimulation led to increases at both dmPAG and dlPAG. Surprisingly,
      neither escape- nor freezing-provoking stimulations altered Fos expression in the
      central nucleus of amygdala (CeA). Escape-provoking stimulation caused increased
      Fos expression in the ventromedial hypothalamus (VMH), dorsal premammilary
      nucleus (PMd) and in the cuneiform nucleus. Significant increases in Fos labeling
      were found in the dmPAG and PMd following freezing-provoking stimulation.
      Therefore, the present data support the notion of a neural segregation for
      defensive behaviors in the dorsal columns of PAG, with increased Fos expression
      in the dmPAG following freezing, while dlPAG is affected by both freezing and
      escape responses. dlPAG, CnF, VMH and PMd are part of a brain aversion network
      activated by fear unconditioned stimuli. The present data also suggests that the
      defensive responses generated at the dlPAG level do not recruit the neural
      circuits of the vlPAG and CeA usually activated by conditioned fear stimuli.

PMID- 14698350
TI  - Chronic psychosocial stress down-regulates central cytokines mRNA.
AB  - Brain cytokines have been implicated in brain plasticity and mood alterations. We
      present here the first evidence of a chronic stress-induced modulation of central
      cytokines, in absence of experimentally induced inflammatory processes. Several
      brain areas were extracted from stressed and control mice and cytokines mRNA
      analyzed with semi-quantitative RT-PCR. Mice subjected to chronic psychosocial
      stress showed decreased interleukin (IL)-1beta mRNA levels in the hippocampus,
      decreased IL-1Receptor antagonist in the striatum and pituitary, decreased tumor
      necrosis factor (TNF)-alpha in the striatum and hippocampus, and decreased
      glucocorticoid receptor (GR) in the striatum and hippocampus compared to group
      housed sibling mice. An independent group of mice subjected to chronic
      psychosocial stress also showed increased plasma corticosterone. These findings
      may open new perspectives for understanding the pathophysiological basis of
      chronic stress-induced disorders.

PMID- 14698352
TI  - Inverse relation between postural variability and difficulty of a concurrent
      short-term memory task.
AB  - We measured postural stability while participants simply stood or stood while
      performing a digit rehearsal task of varying levels of difficulty in order to
      examine the effects on postural control of concurrent short-term memory demands.
      The rehearsal task manipulation avoided factors that contaminate postural sway
      measurements, such as vocal articulation or visual fixation during posture data
      collection. When participants performed the more difficult digit tasks (longer
      digit strings), postural sway was reduced relative to when performing an easy
      version of the task (few digits). The results identified a complex relation
      between postural control and cognitive or attentional demands.

PMID- 14698353
TI  - Open field locomotor effects in rats after intraventricular injections of ethanol
      and the ethanol metabolites acetaldehyde and acetate.
AB  - The typical response to acute peripheral administration of low to high doses of
      ethanol in rats is a dose-dependent depression of motor activity. Nevertheless,
      recent studies indicate that intraventricular (ICV) injections of ethanol can
      produce signs of behavioral activation. In addition, considerable evidence
      indicates that brain metabolism of ethanol is involved in modulating some of the
      behavioral effects of this drug, which suggests that ethanol may have active
      metabolites with central actions. The present study was undertaken to investigate
      the effects of ICV ethanol, and its two major metabolites acetaldehyde and
      acetate, on open field locomotor activity in rats. Male Sprague-Dawley rats
      received different doses of ethanol, acetaldehyde or acetate ICV and immediately
      were placed in an open field chamber in which locomotion was measured. Rats
      injected with ICV ethanol or acetaldehyde showed an inverted U-shaped dose
      response curve, with moderate doses increasing motor activity. In contrast,
      acetate produced a dose-dependent decrease in motor activity. These results
      demonstrate that central administration of low doses of ethanol can increase
      locomotor activity in rats, and suggest that acetaldehyde may be an active
      metabolite of ethanol that also can facilitate locomotor activity. Moreover, it
      is possible that some of the motor suppression or sedation produced by ethanol is
      due to the central actions of acetate.

PMID- 14698354
TI  - Fos and FRA protein expression in rat precerebellar structures during the
      Neurolab Space Mission.
AB  - Changes in gene expression were examined in precerebellar structures during and
      after space flight. These structures included the inferior olive (IO), the source
      of climbing fibers, and the lateral reticular nucleus (LRt) and basilar pontine
      nuclei (PN), sources of mossy fibers. We examined two immediate early gene
      products with two different time courses of expression: Fos, which persists only
      for a few (6-8)h after activation and FRA expression, which lasts for longer
      periods of time, i.e. hours and/or days after activation. Gravity effects on Fos
      and FRA gene expression were evident in vestibular and visual areas of the IO,
      including the dorsomedial cell column, the beta subnucleus and the dorsal cap of
      Kooy of the medial nucleus (which projects to the flocculonodular lobe, i.e. to
      the vestibular area of the IO involved in the olivary control of the vestibulo
      ocular reflex (VOR)). Gene expression also affected the subnuclei A, B, and C and
      the caudal part of the medial IO. These olivary regions do not receive vestibular
      afferents, but rather spinal afferents, and are particularly involved in the
      olivary control of the vestibulospinal reflex (VSR). Changes in Fos expression
      were also observed in the LRt and the PN. We suggest that sensory substitution,
      in which signals produced by a subject's own activity replace activity normally
      provided by macular stimulation, contributes to the recovery of microgravity
      related postural and motor deficits. While no consistent increases in FRA
      expression occurred in vestibular IO regions 24h after launch, consistent
      increases in FRA expression occurred 24h after landing. We hypothesize that this
      asymmetrical pattern of gene expression resulted from (i). tonic microgravity
      experienced after launch counteracting the effects of increased phasic
      gravitational forces experienced during launch, and (ii). the tonic gravitational
      field experienced after landing potentiating the effects of increased phasic
      gravitational forces experienced during landing. The specificity of these results
      is demonstrated by an absence of direct gravity-related changes in Fos expression
      in other precerebellar structures such as the external cuneate nucleus, group X,
      and the dorsal column nuclei that transmit exteroceptive and proprioceptive
      signals to thalamic nuclei and somatosensory areas of the cerebral cortex. The
      gravity-related Fos and FRA expression changes in the IO and the LRt seen here
      are of interest in view of the important role their projections play in adaptive
      gain changes of the VOR and VSR during sustained visuo-vestibular and neck
      vestibular stimulation.

PMID- 14698355
TI  - Method for measuring neurotoxicity of aggregating polypeptides with the MTT assay
      on differentiated neuroblastoma cells.
AB  - Reliable in vitro assays are essential for study of the effects of neurotoxic
      compounds such as beta-amyloid peptides (Abeta). The MTT assay has been used in
      cultures of different cells, e.g. SH-SY5Y neuroblastoma cells, for the
      quantitative measurement of Abeta toxicity. In our laboratory differentiated SH
      SY5Y cells were used in the MTT assay. Cell differentiation with 10 microM all
      trans-retinoic acid resulted in a constant cell number. The cells possess highly
      developed neurites and exhibit high sensitivity against Abeta. Owing to the
      constant cell number in differentiated SH-SY5Y cultures the decrease of the redox
      activity is directly proportional to the neurotoxicity of the substances, no
      correction is needed. The results of the MTT assay of Abeta peptides on
      differentiated SH-SY5Y cells displayed a good correlation also with the in vivo
      results. The present experiments reveal an effective assay for the study of
      potentially neurotoxic compounds.

PMID- 14698356
TI  - White matter lesions in Fabry disease occur in 'prior' selectively hypometabolic
      and hyperperfused brain regions.
AB  - Fabry disease is an X-linked disorder associated with early onset stroke. We
      previously found a significantly elevated cerebral blood flow (CBF) in patients
      with Fabry disease. We set to determine whether elevated resting CBF in Fabry
      disease is primarily a cerebrovascular abnormality or is secondary to enhanced
      neuronal metabolism. The relationship of cerebral metabolism and blood flow to
      Fabry leukoencephalopathy was also investigated. We measured the global and
      regional cerebral metabolic rate of glucose using 18-fluoro-deoxyglucose (FDG)
      and PET in 16 patients with Fabry disease (7 patients with leukoaraiotic lesions
      and 9 without) and in 7 control subjects. MRI fluid attenuated inversion recovery
      (FLAIR) studies were also performed in the patient and control groups. All
      control subjects had normal MRI FLAIR studies with no high-signal deep white
      matter lesions (WML). Patients were partitioned into FLAIR lesion and non-FLAIR
      lesion groups. We found no evidence of cerebral glucose hypermetabolism in Fabry
      disease. On the contrary, significantly decreased regional cerebral glucose
      metabolism (rCMRGlu) was found particularly in the deep white matter in the Fabry
      non-lesion group and exacerbated in the lesion group. Lesion-susceptible regions
      were relatively hyperperfused in non-lesion patients compared to the control
      group. We conclude that the elevated rCBF and decreased white matter rCMRGlu
      indicates a dissociation between metabolism and blood flow suggesting chronic
      deep white matter metabolic insufficiency.

PMID- 14698357
TI  - The impact of self-hypnosis and Johrei on lymphocyte subpopulations at exam time:
      a controlled study.
AB  - In a prospective randomised controlled trial, 48 students were randomly assigned
      to stress reduction training before exams with self-hypnosis, Johrei or a mock
      neurofeedback relaxation control. Peripheral blood lymphocyte subpopulations and
      self-reported stress (Perceived Stress Scale) were measured before training and 1
      2 months later as exams approached. Absolute number and percentages of
      CD3(+)CD4(+) and CD3(+)CD8(+) T lymphocytes, CD3(-)CD56(+) Natural Killer cells
      (NK cells) and NK cell cytotoxic activity was measured from venous blood.
      Stressed participants showed small but significant declines in both CD3(-)CD56(+)
      NK cell percentages and NK cell cytotoxic activity levels while CD3(+)CD4(+) T
      cell percentages increased, changes supported by correlations with perceived
      stress. The effects of stress were moderated in those who learned Johrei at exam
      time; 11/12 showed increases in CD3(-)CD56(+) NK cell percentages with decreased
      percentages of CD3(+)CD4(+) T cells, effects not seen in the relaxation control
      group. Stress was also buffered in those who learned and practised self-hypnosis
      in whom CD3(-)CD56(+) NK cell and CD3(+)CD4(+) T cell levels were maintained, and
      whose CD3(+)CD8(+) T cell percentages, shown previously to decline with exams,
      increased. The results compliment beneficial effects on mood of self-hypnosis and
      Johrei. The results are in keeping with beneficial influences of self-hypnosis
      and provide the first evidence of the suggestive value of the Japanese Johrei
      procedure for stress reduction, which clearly warrants further investigation.

PMID- 14698358
TI  - Postsynaptic dopamine (D(2))-mediated behavioural effects of high acute doses of
      artemisinin in rodents.
AB  - Artemisinin or qinghaosu is the active principle of quinghao (Artemisia annua L.)
      developed from Chinese traditional medicine, which is now widely used around the
      world against falciparum malaria. Behavioural effects of high acute doses of
      artemisinin were studied on spontaneous motor activity (SMA), exploratory
      behavior, apomorphine-induced stereotype behavior and pentobarbital sleeping time
      in mice and rats in order to provide additional evidence on its safety profile on
      the central nervous system (CNS). Effects of the drug on bromocriptine-induced
      hyperactivity in short term reserpinised mice were also evaluated.
      Intraperitoneal (i.p.) injection of artemisinin at doses of 50 and 100mg/kg,
      significantly (P<0.05) reduced the SMA in mice, prolonged the pentobarbital
      sleeping time in rats, and attenuated the apomorphine-induced stereotypy in mice.
      Mice pretreated with reserpine, showed a significant decrease in locomotor
      activity compared to the saline-treated group. Bromocriptine, a D(2) receptor
      agonist, induced locomotor activity in mice pretreated with reserpine which was
      attenuated by artemisinin. The results suggest that artemisinin possesses
      sedative property, which may be mediated via postsynaptic dopamine (D(2))
      receptor in the CNS.

PMID- 14698359
TI  - The mother of all breathing problems.

PMID- 14698360
TI  - Role of cross-allergies to latex in clinical routine of anesthesia.
AB  - STUDY OBJECTIVE: To determine the applicability and reliability of a screening
      questionnaire to detect patients at high-risk of latex allergy; to assess the
      importance of other allergies such as profilin allergies (pollinosis) for
      presence of latex sensitization; and to determine the clinical effectiveness of
      preemptive avoidance of latex exposure in high-risk patients. DESIGN:
      Prospective, clinical trial. SETTING: Operative theater of a university hospital.
      PATIENTS: 95 adult patients. INTERVENTIONS: Patients were preoperatively screened
      and classified for present latex allergy (high-risk and low-risk group) according
      to a specially designed screening questionnaire. Anesthesia and surgery in the
      high-risk group were performed strictly avoiding latex-containing materials. The
      low-risk group (other allergies including pollinosis) received routine treatment,
      without latex-avoidance. Effects of latex avoidance or exposure were evaluated by
      measuring specific IgE titers perioperatively. MEASUREMENTS AND MAIN RESULTS:
      According to the questionnaire, 45 patients at high risk were defined. Validity
      of classification of high-risk patients is supported by significantly higher
      total IgE and latex and grass profilin specific IgE compared to the low-risk
      group. There were no significant differences in other profilin-specific IgEs. In
      one case of severe anaphylactic reaction a drop of latex-specific IgE during
      surgery could be observed. CONCLUSION: The questionnaire allowed the
      identification of most patients at high risk for latex allergy. In isolated
      pollinosis no changes in any specific IgE levels were detectable. Strict
      avoidance of perioperative latex exposure in high-risk patients increases safety
      during anesthesia and surgery.

PMID- 14698361
TI  - Sleeping characteristics of adults undergoing outpatient elective surgery: a
      cohort study.
AB  - STUDY OBJECTIVE: To describe sleeping patterns of adults before and after
      outpatient surgery. DESIGN: Observational cohort study. SETTING: Outpatient
      surgical facility. PATIENTS: 127 consenting adults, including 92 surgery patients
      and 35 community controls. INTERVENTIONS: Participants' sleep was measured for
      two days before and 2 days after outpatient surgery. MEASUREMENTS: Sleep was
      measured using actigraphy; additional measurements were made of anxiety (STAI),
      pain and energy (VAS), recovery (PHRI), and sleep history. MAIN RESULTS:
      Approximately 23% of patients experienced clinically significant sleep impairment
      after surgery, a more difficult recovery, increased pain, and lower energy. In
      contrast, only 2.9% of the community control group experienced clinically
      significant sleep impairment during the same time period. Also, patients in the
      surgery group experienced significantly more True Wake Time postoperatively than
      did control patients (p = 0.029). The surgery group also experienced more Night
      Awakenings >5 minutes than the control group (p = 0.006), but not more overall
      Night Awakenings (p = 0.106). Finally, of the patients in the surgery group,
      those who had higher state anxiety in the holding area also had more difficulty
      sleeping over the 4-day monitoring period (True Sleep Time was lower, 352 +/- 187
      vs. 229 +/- 225, p = 0.009). CONCLUSIONS: A moderate proportion of adults
      experience postoperative sleeping problems.

PMID- 14698363
TI  - Criteria for immediate postoperative extubation in adult recipients following
      living-related liver transplantation with total intravenous anesthesia.
AB  - STUDY OBJECTIVE: To evaluate whether our criteria for immediate postoperative
      extubation predicts successful extubation in living-related liver transplantation
      of the right lobe, and to test the effects of our standardized anesthetic
      technique on the success of immediate postoperative extubation. DESIGN: Open
      label, descriptive study. SETTING: University hospital. PATIENTS: 6 ASA physical
      status III and IV patients with end-stage liver disease undergoing living-related
      liver transplantation of the right lobe. INTERVENTIONS: Patients received a
      standardized anesthetic technique with propofol, remifentanil, and cisatracurium.
      They were extubated when they met our criteria for immediate postoperative
      extubation: good donor liver function, <10 U packed red blood cells administered,
      hemodynamic stability, and alveolar-arterial oxygen gradient <200 mmHg.
      MEASUREMENTS AND MAIN RESULTS: At the end of surgery, four of the six patients
      fulfilled our criteria for immediate postoperative extubation. They were
      uneventfully extubated rapidly after surgery and soon arrived in the intensive
      care unit. Their postoperative stay in the operating room was only 36 minutes
      (range: 30 to 42 min). No patient required reintubation in the operating room or
      the intensive care unit. They had no recorded hemodynamic or respiratory problems
      postoperatively. CONCLUSIONS: Immediate extubation of selected living-related
      liver transplant recipients can be a safe procedure. Anesthetic management to
      immediate extubation seems appropriate and the derived guidelines appear
      acceptable.

PMID- 14698362
TI  - Epidural infusion of clonidine or clonidine plus ropivacaine for postoperative
      analgesia in children undergoing major abdominal surgery.
AB  - STUDY OBJECTIVE: To investigate the analgesic efficacy and safety of epidural
      infusion of clonidine in children undergoing major abdominal surgery. DESIGN:
      Randomized open-label study. SETTING: Postoperative anesthetic unit and pediatric
      ward of a metropolitan hospital. PATIENTS: Forty children aged 0 to 3 years
      undergoing major abdominal surgery. INTERVENTIONS: Children were randomly
      allocated to receive a 24-hour epidural infusion of clonidine 1 microg.mL(-1) at
      rate of 0.2 mL.kg -1.h -1 preceded by a bolus of 2 microg.kg -1 (CLON group) or a
      mixture of clonidine 1 microg.mL -1 and ropivacaine 0.1% at rate of 0.2 mL.kg 
      1.h -1. Both groups received intravenous (IV) ketoprofen 2 mg.kg -1 every 8
      hours. Breakthrough pain was treated with IV tramadol 1 mg.kg(-1). MEASUREMENTS:
      Tramadol requirement, sedation and respiratory and hemodynamic changes were
      measured. MAIN RESULTS: Approximately 77% and 59.3% of the CLON and CLON+ROPIV
      groups, respectively, required no tramadol or only one dose over a 24-hour
      period. Except for those patients who exhibited frequent coughing during the
      night (4 and 5 patients in the CLON and CLON+ROPIV groups, respectively), no
      study patients required an analgesic and all had good sleep quality during the
      first night. Sedation and decreased systolic blood pressure were observed after
      the clonidine bolus was given. CONCLUSION: For children undergoing major
      abdominal surgery, the addition of epidural infusion of clonidine or clonidine
      plus ropivacaine to IV ketoprofen provided good analgesia quality for
      postoperative rest pain.

PMID- 14698364
TI  - Diabetes attenuates the hemodynamic stabilizing effects of oral clonidine during
      off-pump coronary artery bypass surgery.
AB  - STUDY OBJECTIVE: To investigate the influence of diabetes mellitus on the
      hemodynamic-stabilizing effect of clonidine during off-pump coronary artery
      bypass (OPCAB) surgery. DESIGN: Prospective study. SETTING: Public, university
      affiliated hospital. PATIENTS: 40 patients (32 male, 8 female) scheduled for
      OPCAB surgery. INTERVENTIONS AND MEASUREMENTS: Patients were divided into equal
      groups of diabetic and nondiabetic patients. All patients were given 150 microg
      oral clonidine 1 hour before induction. Anesthesia was induced and maintained
      with fentanyl, propofol, and sevoflurane. Propranolol was administered
      intermittently to maintain an adequate heart rate (HR; 50 to 70 bpm).
      Preoperative demographic data (fasting blood glucose concentration and hemoglobin
      A1c), dose of intraoperative drugs (propofol and propranolol), and outcome data
      (duration of intubation and duration of hospital stay after surgery) were
      analyzed. MAIN RESULTS: In the diabetic and nondiabetic groups, the mean (+/-SD)
      plasma glucose values were 7.8 +/- 2.3 mmoL. L(-1) and 5.4 +/- 0.7 mmoL. L(-1),
      respectively (p < 0.05), and the mean (+/-SD) HbA1c values were 7.1 +/- 1.3% and
      5.2 +/- 0.4%, respectively (p < 0.05). The mean propofol infusion rate was 2.8 +/
      0.9 mg. kg(-1). h(-1) in diabetic patients and 3.1 +/- 1.0 mg. kg(-1). h(-1) in
      nondiabetics (NS, p > 0.05). The total requirement for propranolol was 5.1 +/-
      2.4 mg in diabetic patients and 1.6 +/- 1.1 mg in nondiabetics (p < 0.05).
      CONCLUSIONS: Diabetes attenuates the hemodynamic stabilizing effects of
      preanesthetic oral clonidine in the clinical setting.

PMID- 14698365
TI  - Preoperative droperidol improved postoperative pain relief in patients undergoing
      rotator-cuff repair during general anesthesia using intravenous morphine.
AB  - STUDY OBJECTIVE: To demonstrate the effect of preoperative and intraoperative,
      small-dose intravenous (IV) droperidol on postoperative pain relief in orthopedic
      patients given general anesthesia with morphine. DESIGN: Randomized, double
      blind, prospective study. SETTING: University-affiliated hospital. PATIENTS: 84
      ASA physical status I and II patients undergoing shoulder rotator-cuff repair
      with general anesthesia. INTERVENTIONS: Patients were randomly assigned to one of
      three groups: Group P (n = 27) wee given droperidol 10 microg/kg IV before skin
      incision; Group A (n = 30) received droperidol 10 microg/kg IV after skin
      incision; and Group C (n = 27) served as controls. General anesthesia consisted
      of sevoflurane and nitrous oxide in oxygen and IV morphine 0.2 mg/kg, which was
      given before skin incision. MEASUREMENTS: The degree of postoperative pain as
      assessed by postoperative pain scores and the number of supplemental analgesics
      given, and the frequency of postoperative nausea and vomiting, nightmares, and
      respiratory depression were compared among the three groups. A p-value < 0.05 was
      considered statistically significant. MAIN RESULTS: The postoperative pain score
      distribution was significantly greater in smaller values in Groups P and A than
      in Group C (p < 0.01). The number of supplemental analgesics given in the first
      18 hours postoperatively was significantly smaller in Group P than in Groups A or
      C (p < 0.05). CONCLUSIONS: Preoperative IV droperidol resulted in improved
      postoperative pain relief inpatients undergoing shoulder rotator cuff surgery
      with general anesthesia using IV morphine.

PMID- 14698366
TI  - Hemoptysis following extracorporeal shock wave lithotripsy: a case of lithotripsy
      induced pulmonary contusion in a pediatric patient.
AB  - We present an unusual case in which a pediatric patient sustained iatrogenic
      pulmonary contusion resulting in severe hemoptysis. Aside from being a rare
      complication of pediatric extracorporeal shock wave lithotripsy, our case is
      unique in regard to the timing and apparent severity of hemoptysis.

PMID- 14698367
TI  - Anesthesia induction for a difficult intubation infant with a laryngeal cyst.
AB  - We report a case of difficult airway in a 37-day-old female with a laryngeal cyst
      during induction of general anesthesia. This case illustrates that upper airway
      obstruction can occur during induction of anesthesia with an unusual infantile
      aryepiglottic fold cyst. In this case, successful orotracheal intubation was
      achieved with spontaneous respiration, and preoperative information on
      orientation of the lesion assisted in positioning the patient to minimize the
      degree of dynamic obstruction.

PMID- 14698368
TI  - Myocardial stunning during abdominal hysterectomy in a healthy woman.
AB  - We report a case of myocardial stunning in a healthy patient. During gynecologic
      surgery, two brief episodes of asystole occurred. Following resuscitation there
      was a short period of severe hypertension and tachycardia. Electrocardiographic
      changes and elevations in troponin T and creatine-kinase-MB were observed.
      Angiography revealed normal coronary arteries and multiple areas of hypokinesis.
      Within 2 weeks, all abnormal values had returned to normal and the patient
      underwent an uneventful surgery.

PMID- 14698369
TI  - Hypertensive crisis inducing rhabdomyolysis during laparoscopic resection of a
      large pheochromocytoma: a case report.
AB  - Intense vasospasm during hypertensive crisis as a cause for rhabdomyolysis has
      been described in ambulatory patients with pheochromocytoma. We report this
      phenomenon as an intraoperative complication in a patient during laparoscopic
      pheochromocytoma resection and discuss patient and procedure related risk
      factors. Unexplained intraoperative hyperkalemia following a severe hypertensive
      episode during surgery may be a first sign of rhabdomyolysis. Anesthesiologists
      should be aware of such a possibility. Intra- and postoperative serial
      electrolyte determinations and if suspected, timely screening for myoglobiuria,
      may aid in early detection and treatment of intraoperative rhabdomyolysis during
      pheochromocytoma resections.

PMID- 14698370
TI  - Massive pulmonary embolism presented as sudden cardiac arrest in the immediate
      postoperative period after laparoscopic hysterectomy.
AB  - A rare case of postoperative cardiac arrest in an otherwise healthy, 49-year-old
      female patient who had a laparoscopic hysterectomy, is presented. The cause of
      cardiac arrest was due to massive pulmonary embolism, which was detected by
      transesophageal echocardiography. Laparoscopic surgery is regarded as a less
      invasive procedure and provides a lower risk for postoperative complications.
      However, our is a case reminer that pneumoperitoneum may interfere with venous
      flow of lower extremities and predispose one to deep vein thrombosis or pulmonary
      embolism.

PMID- 14698371
TI  - Kentucky association of health plans v. Miller: any willing provider laws survive
      supreme court review.

PMID- 14698372
TI  - Airway problems and new solutions for the obstetric patient.
AB  - Anesthesia-related complications are the sixth leading cause of pregnancy-related
      maternal mortality in the United States. Difficult or failed intubation following
      induction of general anesthesia for cesarean delivery remains the major
      contributory factor to anesthesia-related maternal complications. Although the
      use of general anesthesia has been declining in obstetric patients, it may still
      be required in selected cases. Because difficult intubation in obstetric
      anesthesia practice is frequently unexpected, careful and timely preanesthetic
      evaluation of all parturients should identify the majority of patients with
      difficult airway and avoid unexpected difficult airway management.

PMID- 14698373
TI  - Complications of ophthalmologic nerve blocks: a review.
AB  - Complications of ophthalmologic nerve blocks are rare, but they can have serious
      life- and sight-threatening consequences. Knowledge of the potential
      complications is essential for the anesthesiologist who performs ophthalmologic
      nerve blocks. However, most anesthesiologists are unfamiliar with these
      complications because the majority have been reported in the ophthalmology
      literature. We review the complications that may occur during the placement of
      ophthalmologic blocks and their appropriate prompt treatment.

PMID- 14698374
TI  - Comment on "A comparison of the effects of droperidol and the combination of
      droperidol and ondansetron on postoperative nausea and vomiting for patients
      undergoing laparoscopic cholecystectomy".

PMID- 14698375
TI  - Detection of flatus using a portable hydrogen gas analyzer.

PMID- 14698376
TI  - A knotty problem.

PMID- 14698377
TI  - Molecular dynamics in solid pyridoxine as studied by 1H NMR.
AB  - Spin-lattice relaxation times T1 and T1d as well as NMR second moment were
      employed to study molecular dynamics of pyridoxine (vitamin B6) in the
      temperature range 10-350 K. The T1 minimum observed at low temperatures at 200
      MHz is attributed to a motion of methyl group. The motion is interpreted in terms
      of Haupt's theory, which takes into account the tunneling assisted relaxation. At
      low temperatures, where T1 is temperature independent, occupation of the ground
      state only is assumed. A motion of proton of the hydroxyl groups or CH2OH groups
      probably provides additional mechanism of relaxation, in the high-temperature
      region.

PMID- 14698378
TI  - Dynamic aspect of bacteriorhodopsin as a typical membrane protein as revealed by
      site-directed solid-state 13C NMR.
AB  - We demonstrate here a general feature of dynamic aspect of membrane proteins as
      revealed by site-directed 13C NMR studies on bacteriorhodopsin (bR) as a typical
      membrane protein and a variety of mutants at ambient temperature. 13C NMR signals
      of [3-13C]Ala- or [1-13C]Val-labeled proteins were assigned regio-specifically
      with reference to the data of the conformation-dependent 13C chemical shifts from
      model polypeptides, followed by site-specific assignment based on site-directed
      mutants. Revealed picture of membrane protein at ambient temperature is not
      static in contrast to anticipation from crystalline structures but flexible
      enough to undergo a variety of local fluctuations with frequencies from 10(2) to
      10(8)Hz, as pointed out already. This picture was further refined by taking into
      account of residue-specific dynamics of interfacial domains between the surface
      and inner part of the transmembrane helices and conformational fluctuation
      induced by the presence of a kinked structure. The residue-specific dynamics of
      the former was revealed by observation of broadened or suppressed peaks from the
      interfacial domains caused by acquisition of internal fluctuation motions
      interfered with frequencies of proton decoupling or magic angle spinning. The
      presence of such suppressed peaks due to molecular fluctuations in the
      interfacial domains was further confirmed by insensitivity of the peak
      intensities from the interfacial domains in spite of the presence of accelerated
      relaxation rate to nearby residues from surface bound Mn2+ ion. Further,
      conformational change of the transmembrane alpha-helix F due to a plausible
      kinked structure at Pro 186 was confirmed in view of specific displacements of
      Ala 184 and Val 187 13C NMR peaks from chemically synthesized [3-13C]Ala(184)-,
      [1-13C]Val(187)-labeled wild type and P186L mutant of transmembrane fragment
      F(164-194) incorporated into lipid bilayer. It is emphasized that the observed
      displacement of [3-13C]-labeled Ala 184 peak at 17.4 ppm in the presence of
      kinked structure in this model peptide is consistent with that of intact protein
      at 17.27 ppm.

PMID- 14698379
TI  - Calculation of dipolar correlation function in solids with internal mobility.
AB  - A general equation for the dipolar correlation function, to be used to analyze
      various kinds of independent internal motions, described by some correlation
      times tau(cm) (m = 1,2 em...k), has been obtained. The obtained expression has
      been used to analyze the temperature dependencies of different NMR measured
      values: second moment: spin-lattice relaxation times; amplitude of solid echoes
      signals.

PMID- 14698380
TI  - NMR and inelastic incoherent neutron scattering (IINS) studies of monohydroxy-17
      and -21-substituted derivatives of progesterone.
AB  - Internal dynamics of 17- and 21-substituted progesterone derivatives was studied
      by the methods NMR, inelastic incoherent neutron scattering (IINS) and quantum
      chemical calculations. Comparison of the computer simulation of the phonon
      density of states (PDS) spectrum performed by the density functional theory (DFT)
      method with the spectrum obtained after a transformation of the experimental
      results permits an interpretation of subsequent modes. Only for 17OH prg the
      second moment of NMR line decreases to 10 G2 near room temperature, most probably
      because of the oscillations about direction of inter-molecular hydrogen bond.
      Significant mobility of protons in this compound is also confirmed by a low
      intensity of the elastic peak in INS and broadening of this spectrum.

PMID- 14698381
TI  - Visualization of transport: NMR microscopy experiments with model objects for
      porous media with pore sizes down to 50 microm.
AB  - Hydrodynamic flow and electric currents through model porous media were
      investigated. The transport rates through the individual pathways of the pore
      network are determined by the local width of the pore channels and by the driving
      mechanism. The model objects represent quasi two-dimensional random site
      percolation clusters. The calculated design was realized by milling the structure
      in polystyrene sheets. Velocity maps of stationary flow and current density maps
      of stationary currents through the cluster were acquired by magnetic resonance
      imaging methods. The findings were compared to the results of numerical
      simulations based on the same structure. Since the difference in the transport
      patterns of the different driving mechanisms are expected to be more pronounced
      in smaller pore spaces, ultra deep X-ray lithography has been used for the
      fabrication of downsized model objects with a spatial resolution of better than
      50 microm and an aspect ratio as large as 20. First results obtained with these
      objects are reported.

PMID- 14698382
TI  - The swelling properties of hydroxypropyl methyl cellulose loaded with
      tetracycline hydrochloride: magnetic resonance imaging study.
AB  - Magnetic resonance imaging was used to study the behavior of the gel layer
      thickness in hydroxypropyl methyl cellulose (HPMC) matrices loaded with different
      amounts of soluble tetracycline hydrochloride. The time dependence of the
      diffusion front, effective T2, and proton-density analysis clearly indicates a
      Case II diffusion mechanism in the system composed of water solution of
      hydrochloric acid (pH = 2) and HPMC. The solvent penetration front was used to
      describe the swelling properties as well as the integrity of the HPMC matrices.
      The results show that the tetracycline hydrochloride decreases the resistance of
      the HPMC network structure against the movement of solvent molecules. On the
      other hand the swelling properties of the matrix increase with the amount of drug
      in the matrix.

PMID- 14698383
TI  - NMR study of molecular dynamics in selected hydrophilic polymers.
AB  - The temperature dependencies of the 1H spin-lattice relaxation times T1 and of
      the proton NMR second moment M2 in the temperature range from about 90 to 420 K
      were measured for methyl cellulose, hydroxypropyl cellulose and hydroxypropyl
      methyl cellulose. The proton spin-lattice relaxation measurements reveal two
      minima due to the C3 reorientation of the methyl groups of the methoxy,
      methylenemethoxy or propylene oxide groups and the restricted motion of the
      segment of the polymer chain. The activation energy barriers for these motions
      were calculated.

PMID- 14698384
TI  - Proton longitudinal NMR relaxation of poly(p-phenylene sulfide) in the laboratory
      and the rotating frames reference.
AB  - Spin-lattice NMR relaxation times T1 in the laboratory frame and T1rho(off) as
      well as T1rho(off) in the rotating frame off-resonance were employed to the study
      of molecular dynamics of both pristine PPS and thermally treated poly(p-phenylene
      sulfide) (PPS). The temperature dependence of T1 was exponential in the whole
      temperature range studied, whereas T1rho only in low temperatures. In the high
      temperature range the distribution of relaxation times T1rho and correlation
      times tau(c) as well as activation energy Ea was observed. The distribution of
      activation energy determined from T1 minima at 15 and 30 MHz and from low
      temperature slopes of T1rho dependence as well as from spectral density functions
      (estimated from proton off-resonance technique) was attributed to the
      reorientation of phenylene groups around the sulfur-phenyl-sulfur axis in
      amorphous and crystalline phases of PPS. Furthermore, it is suggested that an
      additional relaxation mechanism related to interactions of protons with
      paramagnetic centers is operative in a low temperature range. After thermal
      treatment of PPS the low temperature minima disappeared and the relaxation times
      shortened in the low temperature regime. Both these facts were attributed to an
      increased contribution of spin diffusion in the relaxation process.

PMID- 14698385
TI  - Investigation of metabolic changes in irradiated rat brain tissue by means of 1H
      NMR in vitro relaxation study.
AB  - The effect of irradiation on concentrations and relaxation behaviour of brain
      metabolites was studied by means of high-resolution 1H NMR in vitro. The studies
      were performed on rat brains irradiated with the doses of 20 Gy applied in
      fractions of 2 Gy. Standard procedures were used to obtain HClO4 extracts of rat
      brains. The 1H NMR studies of the extracts solutions in D2O were performed using
      a Varian Inova-300 NMR spectrometer. The integral intensities of the metabolite
      signals were found to change during the irradiation cycle and after it. These
      changes are accompanied by the variations in the T1 relaxation times. N
      acetylaspartate, glycerophosphocholine, phosphocholine, choline, creatine and
      phosphocreatine, myoinositol and taurine were analysed as potential markers of
      irradiation injury.

PMID- 14698386
TI  - Comparative experimental analysis of composite pulses in 14N NQR.
AB  - Experimental results of comparing composite pulses in nitrogen-14 NQR, that are
      analogous to common 90 degrees RF pulses in powder, are presented. All tested
      pulses have been taken from publications in journals. Comparative diagrams of the
      measurement results for induction signals and echo signals are presented. The
      results of the measurements demonstrate that the best outcomes are achieved when
      the composite pulse (45)0(95)180(164)0 is used.

PMID- 14698387
TI  - NMR relaxation dispersion of vulcanized natural rubber.
AB  - The dependence of the 1H spin-lattice relaxation time on the magnetic field
      strength has been determined for linear and cross-linked polyisoprene for Larmor
      frequencies between 5 kHz and 20 MHz. Universal power-law relations are found for
      all temperatures and cross-link densities under investigation and are compared to
      published results of rotating-frame experiments on similar natural rubber
      samples. The shape of the individual dispersion functions can be superposed into
      a master curve using appropriate shift factors. While addition of filler
      particles even at large weight fractions has only a minor effect on the
      relaxation times, uniaxial deformation and swelling are demonstrated to alter the
      molecular dynamics significantly.

PMID- 14698388
TI  - 125Te NMR tomography of [Re6] cluster in Re6Te15 and related cluster compounds.
AB  - The static and magic angle spinning NMR solid-state spectra of Re6Te15 and a
      series of Re(6)-Te cluster compounds demonstrate the positive and negative 125Te
      NMR chemical shifts indicating that the [Re6] cluster distorts strongly magnetic
      field at the neighboring Te sites. The local magnetic field is decreased at the
      facial tellurium sites (Teface) and enhanced at the apexial tellurium sites
      (Teapex). The facial and sagittal sections of the Re(6)-Te clusters were
      reconstructed from analysis of Teface and Teapex NMR spectra, respectively.

PMID- 14698389
TI  - Simple two-pulse time-reversal sequence for dipolar and quadrupolar-coupled spin
      systems.
AB  - We demonstrate, both theoretically and experimentally, that two-pulse sequence
      (2n+1) X 90 degrees(Y) - 90 degrees(X) -Acq(t) without delay between pulses,
      yields the reverse of time evolution of spin system with dipolar and quadrupole
      interactions. This process results in refocusing of the spin magnetization into
      magic echo at te = t1/2 after the second pulse, where t1 is the length of the
      first pulse.

PMID- 14698390
TI  - NMR relaxometry study of cement hydration in the presence of different oxidic
      fine fraction materials.
AB  - NMR relaxometry has been applied to study hydrating cements for about 25 years
      now. The most important advantage over other experimental approaches is the
      possibility to conduct non-destructive measurements with a time resolution of
      minutes. NMR relaxometry data thus can help to identify details in the time
      course of cement hydration that possibly would be overlooked in other experiments
      with lower temporal resolution. Time-resolved information on cement hydration
      kinetics can provide interesting insights into the impact of oxidic additive
      materials on cement hydration. For PbO, a very strong delay was observed which
      then was systematically studied. An explanation for this delay is suggested.

PMID- 14698391
TI  - 3D MR imaging of dental cavities-an in vitro study.
AB  - A 3D spin-echo (3D SE) pulse sequence was used on a 4.7 T research MRI system to
      produce images of extracted human first molar tooth placed in CuSO4 water
      solution. The maximal resolution achieved was 35 x 63 x 300 microm3 in read and
      two phase directions, respectively. The high-intensity signal from water in
      solution together with the lack of signal from mineralized tooth tissue produce
      very good contrast allowing to visualize topography of outer and inner surfaces
      of the tooth. The 3D MR data were median filtered, binarized and then divided
      into separate segments corresponding to the inner tooth cavities and the hard
      tooth tissue. The topography of the root canals was visualized and the canals
      volume was calculated. The presented technique may be used for quantitative
      analysis of the root canal cavities shape and volume. The results of such an
      analysis may be applied for estimation of the quality of the impressional mapping
      methods in restorative dentistry or as an alternative non-impressional 3D mapping
      method.

PMID- 14698392
TI  - Analysis of the diffusion weighted MR microscopy data of excised spinal cord of a
      rat on the basis of the model of restricted diffusion.
AB  - Anisotropic diffusion in the excised rat spinal cord saturated with 0.9% saline
      was investigated using MR microimaging with b-values up to 8000 s/mm2 for
      different diffusion times. Non-exponential transversal diffusion decay found in
      white matter (WM) and gray matter (GM) was fitted with 2 components (the "fast"
      and the "slow"). Significantly smaller non-exponential dependence was found for
      the longitudinal diffusion in the WM. Obtained results corresponding to
      restricted diffusion in the range from approximately 2 to approximately 7 microm
      were correlated with axon diameter distribution in the WM obtained from
      transmission electron micrographs. It was concluded that observed diffusion
      anisotropy in the spinal cord might be entirely explained by presence of the slow
      transversal component, arising from the restricted diffusion. The strict
      analytical description of the diffusion decay in nervous tissue requires taking
      into account continuous distribution of the space-scale of the restricting
      barriers. The simplified two-component analysis may be applicable for
      visualization of the nervous tissue in clinical practice.

PMID- 14698393
TI  - Modified steady-state free precession pulse sequences for the detection of pure
      nuclear quadrupole resonance.
AB  - Modifications of the steady-state free precession multi-pulse technique for the
      effective detection of the nuclear quadrupole resonance (NQR) signals are
      proposed. These modifications are based on the use of composite pulses and enable
      the suppression of the coherent noise signals such as the magneto-acoustic and
      piezo-electric signals or the ringing signal from the NQR probe. Experimental
      results of applying the proposed technique to nitrogen-14 NQR in the sample of
      C6H12N4 are also presented and convincingly demonstrate its effectiveness.

PMID- 14698394
TI  - Study of quasistationary and stationary states in the short-repetition-time
      sequences in the NQR of nitrogen.
AB  - Experimental and theoretical study of quasistationary and stationary states that
      are established in the quadrupolar spin system subjected to the steady-state
      sequences which consist of a chain of identical pulses and can be preceded by a
      preparatory pulse. We have obtained theoretical expressions for the magnetisation
      of the spin system that take into account off-resonance conditions during the
      effect of the pulses. Frequency dependencies of the NQR signal in the
      quasistationary and stationary states are shown for C3H6N6O6 (RDX) and NaNO2, and
      compared with theoretical results.

PMID- 14698395
TI  - Spin-echoes in nitrogen-14 quadrupolar spin-system with axially symmetric
      electric field gradient tensor.
AB  - The behaviour of the magnetisation in the spin-1 system with the axial symmetry
      of the electric field gradient (EFG) tensor was analysed theoretically. The
      behaviour of the NQR signals in hexamethylenetetramine (C6H12N4) was also studied
      experimentally using the pulse NQR technique and sensitive equipment. It was
      shown that the axial symmetry of the EFG in a sample could not be the reason why
      spin-echo signals were not observed in conventional pulse experiments for the
      same type of sample. A very short spin-spin relaxation time T2 seems to be the
      reason of that. The signal-to-noise ratio was sufficient for measuring T2 in
      C6H12N4, which had not been reported earlier. Experimental results of applying
      certain pulse sequences to the 14N NQR in a sample are also presented.

PMID- 14698396
TI  - NMR strong off-resonance irradiation without sample overheating.
AB  - A prototype NMR probe for long RF pulse has been constructed. Its main elements
      are two coils mounted in the concentric position. The first bigger coil is wound
      around a glass dewar tube and the second smaller coil is placed inside the dewar.
      These two coils are thermally isolated by the dewar. A long and strong RF pulse
      is applied to the bigger coil. The smaller detection coil inside the dewar
      contains a sample and to this coil a short RF pulse is applied. The two coils are
      independently tuned and electrically isolated. During the operation of the strong
      RF pulse the smaller coil has a high resistance to ground (very low Q factor) and
      does not absorb energy from the bigger coil. During the operation of the short on
      resonance RF pulse the bigger coil is detuned to a higher frequency, but the
      resonance circuit with the small coil is in the electrical resonance. The NMR
      probe may be used in off-resonance experiments in which long and strong RF pulses
      are applied to the bigger coil and thereby the problem of the sample overheating
      is avoided.

PMID- 14698397
TI  - NMR study of triglycine sulphate (TGS) in electric field perpendicular to the
      ferroelectric axis.
AB  - The electric field applied perpendicular to the ferroelectric axis bHOP (in
      Hoshino, Okaya, Pepinsky notation) of the TGS crystal, results new domain
      structure-striped domains with walls parallel to the cHOP axis. The process is
      accompanied by changes of the dielectric properties. We present the results of
      NMR study of TGS crystal with electric field applied parallel to the cHOP or to
      the cHOP x bHOP directions. After 12 h application of the DC field, a decrease in
      amplitude of the 1H NMR central line is observed.

PMID- 14698398
TI  - 1H NMR studies on molecular motions of 4-aminopyridinium and pyrrolidinium
      cations in new ferroics.
AB  - The aim of the study was to check the effect of the cation on the molecular
      dynamics of the anion, which is not directly observed, in different phases of the
      following compounds: (C4H8NH2)SbCl6(C4H8NH2)Cl, (C4H8NH2)SbCl6 and (4-apyH)ClO4,
      (4-apyH)SbCl4.

PMID- 14698399
TI  - Van Vleck second moments and hydrogen diffusion in YH2.1--measurements and
      simulations.
AB  - Proton magnetic resonance absorption spectra of yttrium dihydride (YH(2+x)), with
      x = 0.10, were recorded in the temperature ranges 4.2-310 K at 36.01 MHz and 150
      400 K at 299.8 MHz. The evidence of proton self-diffusion follows from the
      changes of linewidth with temperature. The second moment of the resonance lines
      was determined from the experimental spectra and was compared with values
      calculated from the crystallographic data. The averaging effect of diffusion on
      the second moment was taken into account through Monte Carlo simulations of the
      diffusion process. The simulation was performed in a block of unit cells 5 x 5 x
      5 with periodic boundary conditions. They compensated the effect of finite
      dimensions of the block. The calculated temperature dependence of the proton
      second moment values was fitted to the experimental ones. The fitting parameters
      were: the attempt frequency v0 and the activation energy Ea for hydrogen
      diffusion, assuming Arrhenius behavior of the jump frequencies vc = v0 exp(
      Ea/k(B)T). In these preliminary studies, the Monte Carlo simulations were
      performed for tetrahedral-octahedral exchanges while direct tetrahedral
      tetrahedral jumps were neglected for simplicity. Three models of hydrogen
      diffusion, differing in the maximum jump lengths allowed for a given model, were
      considered. These lengths were taken as the distances from the hydrogen
      attempting to jump to the first (1NN), second (2NN), and third (3NN) nearest
      neighbor position able to accept the jumping atom. Assuming the same attempt
      frequency v0 = 6.0 x 10(12)s(-1) for all three models, the activation energies
      giving the best fit to experimental data were 0.5, 0.54, and 0.55 eV for 1NN,
      2NN, and 3NN models, respectively.

PMID- 14698400
TI  - 3D micron-scale MRI of single biological cells.
AB  - We report MRI microscopy images of single biological cells with micron-scale
      resolution in all three dimensions. Sub-cellular organelles are observed,
      including a spiral-shaped array of chloroplasts on the inner surface of the cell
      wall of a Spirogyra alga.

PMID- 14698401
TI  - The effect of polysialic acid on molecular dynamics of model membranes studied by
      31P NMR spectroscopy.
AB  - The paper reports the results of our study on the dynamics of model phospholipid
      membranes studied by 31P NMR spectroscopy. The 31P NMR spectra of multilamellar
      vesicles in temperatures below the main phase transition of PC are reported. The
      31P NMR spectra revealed changes caused by an increase of the membrane fluidity
      when polysialic acid (polySia) was applied as a modifying agent. The presence of
      polySia in the external environment of the phospholipid vesicles changes the
      motional freedom in the region of phosphate group of lipids. Increase of
      polysialic acid concentration changes structural properties of a membrane by
      increasing its fluidity.

PMID- 14698402
TI  - 1H and 2H NMR studies of benzene confined in porous solids: melting point
      depression and pore size distribution.
AB  - The pore size distributions of four controlled pore glasses and three silica gels
      with nominal diameters in the range 4-24 nm were determined by measuring the 1H
      and 2H NMR signals from the non-frozen fraction of confined benzene and
      perdeuterated benzene as a function of temperature, in steps of ca. 0.1-1 K. The
      liquid and solid components of the adsorbate were distinguished, on the basis of
      the spin-spin relaxation time T2, by employing a spin-echo sequence. The
      experimental intensity curves of the liquid component are well represented by a
      sum of two error functions. The mean melting point depression of benzene and
      perdeuterated benzene confined in the four controlled pore glasses, with pore
      radius R, follows the simplified Gibbs-Thompson equation DeltaT=kp/R with a kp
      value of 44 K nm. As expected, the kp value mainly determines the position of the
      pore size distribution curve, i.e., the mean pore radius, while the transition
      width determines the shape of the pore size distribution curve. The excellent
      agreement between the results from the 1H and 2H measurements shows that the
      effect of the background absorption from protons in physisorbed water and silanol
      groups is negligible under the experimental conditions used. The overall pore
      size distributions determined by NMR are in reasonable agreement with the results
      specified by the manufacturer, or measured by us using the N2 sorption technique.
      The NMR method, which is complementary to the conventional gas sorption method,
      is particularly appropriate for studying pore sizes in the mesoporous range.

PMID- 14698403
TI  - New openings for porous systems research from intermolecular double-quantum NMR.
AB  - It has been recently recognized that residual intermolecular double-quantum
      coherences (iDQcs) provide a novel contrast mechanism to study heterogeneity in
      liquid systems. This is of much interest in the field of the physics of matter
      and biomedicine. Nowadays, literature concerning the behaviour of the iDQc signal
      originated by highly heterogeneous systems such as fluids in porous media is
      scarce. In this paper, we report and discuss our principal results about iDQc
      signal behaviour in confined liquid systems (trabecular bone, travertine, porous
      standard systems) and also some new results obtained on doped water in glass
      capillary pipes.

PMID- 14698404
TI  - Novel pulsed switched power supply for a fast field cycling NMR spectrometer.
AB  - In this paper, we outline the operating principles of a pulsed switched power
      supply for a fast field-cycling nuclear magnetic resonance spectrometer. The
      power supply uses a variant of a four-quadrant chopper with a duty cycle that
      defines the average output current. With this topology only two semiconductors
      are necessary to drive hundreds of amperes with an output power of several
      kilowatts. The output current ripple has a well-defined shape that can be reduced
      to acceptable values by a careful design of the semiconductors' controlling
      circuits and drivers. A power supply prototype was tested with a home build air
      core magnet operating with fields between 0 and 0.21 T. The system is computer
      controlled using pulse generator and data acquisition PC cards, and specific user
      friendly home-developed software. A comparative proton relaxometry study in two
      well-known liquid crystal compounds 5CB and MBBA was performed to check the
      reproducibility of the T1 measurements.

PMID- 14698405
TI  - An NQR study of the polymorphism of triphenylchloromethane.
AB  - This work is a study of the polymorphic transformations of triphenylchloromethane
      (TPCM) as well as the structure and dynamics of this molecular solid. Crystalline
      TPCM has been studied by a variety of techniques and many of its physical
      properties have been characterized. Previous crystallographic studies have
      reported the existence of two crystalline phases. Phase II, stable above 372 K,
      is trigonal with space group P3; and Z = 6. The compound associates pairwise
      (halogen-to-halogen and triphenylmethyl-to-triphenylmethyl) and linearly with all
      carbon-halogen bonds aligned with C3 and S6 axes of the lattice. Below 372 K, a
      triclinic modification (phase III) is found (P1;, Z = 10) where the molecules are
      also aligned pairwise with close Cl cdots, three dots, centered Cl interactions.
      However, the C-Cl bonds were no longer parallel. On the other hand, DTA studies
      have also reported a phase transition at 381 K (to phase I) that can been
      obtained from slow evaporation of pentane or ether solutions. Crystallographic
      information about these phases has not been obtained in the literature. Five NQR
      lines have been observed from liquid nitrogen temperature to 372 K in good
      agreement with phase III that has Z = 10. Above 372 K, three lines are observed
      which are related to phase II. Any effort to observe phase I through NQR failed;
      phase II remains until the sample is melted. Instead, if phase II is cooled down,
      a second-order phase transition to a new phase at 259 K is observed through NQR
      studies. The temperature dependence of experimental data in the phase transition
      region is well explained assuming the transitions occur when molecules in the
      crystal lattice change their direction uniformly with a change in temperature and
      the liberational modes, coupled in an anharmonic way with the uniform mode,
      change their frequencies in such a way that entropy compensates the unfavorable
      potential energy increase due to the uniform angular tilt.

PMID- 14698406
TI  - Studies of water penetration into LDPE--calcium lactate composite.
AB  - Penetration of water into low-density polyethylene-calcium lactate composite is
      studied with NMR techniques. The presence of filler speeds up the water uptake by
      the polymer matrix and facilitates polyethylene degradation. Spatial distribution
      of absorbed water molecules within the composite visualised with MRI corroborates
      differences in dynamical behaviour of the absorbed water molecules revealed by T2
      measurements.

PMID- 14698407
TI  - Molecular dynamics of tert-butyl chloride confined in CPG studied by NMR.
AB  - The molecular dynamics of tert-butyl chloride (TBC) confined to Controlled Pore
      Glass matrices of 25 and 7.5 nm were investigated by measuring NMR linewidths,
      lineshapes, and 1H and 2H spin--lattice relaxation times. The behaviour of
      confined TBC can be explained assuming that the guest molecules form two distinct
      phases; the surface-affected phase, composed of molecules located at the pore
      surface, and the bulk-like phase located at the centre of the pores. The bulk
      like component of confined TBC, at the temperatures corresponding to the phase
      III, is characterized by two dynamically different subphases.

PMID- 14698408
TI  - Field cooled and zero field cooled 207Pb NMR of the relaxor ferroelectric PMN.
AB  - A 2.8 kV/cm electric field has been applied parallel to the external magnetic
      field along the [111] direction of a PMN single crystal and the 207Pb NMR spectra
      were measured at 9.1 T. Whereas the zero field cooled (ZFC) spectrum exhibits a
      Gaussian-like line shape, the FC spectrum clearly shows a two peak structure. One
      of the two peaks coincides with the ZFC spectrum. The other peak is shifted by
      about 100 kHz towards lower frequencies with respect to the ZFC peak and seems to
      be characteristic for the ferroelectric state. The ferroelectric shift agrees
      with the predictions of the spherical random bond-random field model.

PMID- 14698409
TI  - Studies of gelation process investigated by fast field cycling relaxometry and
      dynamical rheology: the case of aqueous low methoxyl pectin solution.
AB  - The Fast Field Cycling Relaxometry and the dynamical rheology were applied to
      study the gelation process in aqueous low methoxyl pectin solution in the
      presence of divalent cations from the calcium chloride. The model-free approach
      to the analysis of 1H NMRD data was used to separate the information on the
      static and dynamic behaviour of the system provided by the dispersion profiles of
      the systems tested. Mechanical spectroscopy was applied as a complementary method
      to probe the network formation. The structural changes were most pronounced for
      the concentration of calcium chloride between 10 and 15 mM (the static parameter
      beta was found to vary from 0.936 x 10(7) to 1.27 x 10(7) 1/s2) revealing the sol
      gel transition on visual inspection. The presence of the gel network was
      confirmed by the rheological measurements. All mechanical spectra exhibited the
      gel like character, and the solid like response was more evident at higher
      concentrations of calcium cations. The mean correlation time <tau(c)> increased
      with increasing salt concentration, but remained unchanged for the concentrations
      above 15 mM. The dynamical changes were most significant at the phase transition
      from the sol to the gel state.

PMID- 14698410
TI  - Rheological and NMR studies of polyethylene/calcium carbonate composites.
AB  - Rheometry, 13C CP/MAS NMR spectra and 1H spin-lattice relaxation times T1 and
      T1rho have been employed to study the structure and molecular dynamics in
      composites of polyethylene (LDPE) with calcium carbonate filler. It has been
      found that the addition of the filler into the polymer leads to an increase in
      composite rigidity and a decrease in mobility in its crystalline regions. The
      presence of the filler affects the crystallization process making the crystal
      structure less perfect and reduces the size of the crystallites.

PMID- 14698411
TI  - Molecular dynamics of n-dodecylammonium chloride in aqueous solutions
      investigated by 2H NMR and 1H NMR relaxometry.
AB  - Molecular dynamics in n-dodecylammonium chloride/water solutions for
      concentrations of 34 and 45 wt% was studied by 2H NMR and by 1H NMR dispersion of
      spin-lattice relaxation in the 2 kHz-90 MHz frequency range. The system exhibits
      a number of lyotropic liquid crystalline phases, which differ in symmetry and
      involve motions characterized by a wide frequency scale. The analysis of 2H NMR
      lineshapes of selectively deuterated DDACl molecules gave us an evidence for
      local trans-gauche conformational changes in the chains, whereas the dispersion
      of spin-lattice relaxation times T1 explored by fast field cycling method
      revealed fast local motions, translational diffusion and collective molecular
      dynamics of the chains. In particular, we have found that the order director
      fluctuation mechanism in smectic and nematic phases dominates spin-lattice
      relaxation below 1 MHz and that local motions and translational diffusion are
      responsible for the spin-lattice relaxation in the higher Larmor frequency range.

PMID- 14698412
TI  - Evaluation of chromosome painting to assess the induction and persistence of
      chromosome aberrations in bone marrow cells of mice treated with benzene.
AB  - Fluorescence in situ hybridization with chromosome-specific painting probes (FISH
      painting) has been successfully applied to detect radiation-induced stable
      aberrations in humans and mice, whereas a few mouse studies with chemicals mostly
      failed to show any increase in chromosome-painting-detectable changes, especially
      in bone marrow cells. To further explore the feasibility of the painting approach
      to detect chemically induced stable aberrations, we treated mice with a single
      high dose of benzene, a potent bone-marrow-targeting clastogenic chemical and
      sacrificed them 24, 36 h or 15 days later to collect bone marrow cells and
      analyze chromatid- and chromosome-type aberrations by FISH painting. In addition,
      we treated another group of mice with 18 daily low doses to show the potential
      for aberration induction and accumulation under chronic exposure. Chromatid-type
      aberrations were significantly increased 24 and 36 h after acute treatment while
      chromosome-type ones were elevated above control values 36 h and 15 days after
      exposure, showing that at least part of benzene-induced chromatid exchanges were
      converted into potentially stable chromosome aberrations. The most common
      aberration was an extra copy of one painted chromosome in a metaphase with the
      euploid number of centromeres which was interpreted as the consequence of a
      symmetric recombination between pericentromeric regions of one painted and one
      unpainted chromatid. Under chronic exposure, neither chromosome- nor chromatid
      type aberrations were significantly elevated over control values, suggesting that
      the probability of enough primary lesions and secondary DNA double strand breaks
      occurring close enough together in time to allow chromosome exchanges to form is
      a critical limiting factor especially in a cycling cell population.

PMID- 14698413
TI  - Mutagenicity of benzo[b]phenanthro[2,3-d]thiophene (BPT) and its metabolites in
      TA100 and base-specific tester strains (TA7001-TA7006) of Salmonella typhimurium:
      evidence of multiple pathways for the bioactivation of BPT.
AB  - Benzo[b]phenanthro[2,3-d]thiophene (BPT), and a number of its metabolites,
      including BPT-3,4-diol, BPT sulfoxide, BPT sulfone, and 3-hydroxyBPT were
      assessed for their mutagenic activity in Salmonella typhimurium strain TA100, and
      S. typhimurium base-specific strains TA7001, TA7002, TA7003, TA7004, TA7005, and
      TA7006. Among the compounds tested in strain TA100, BPT, BPT sulfone, and 3
      hydroxyBPT did not show any significant mutagenic response in the presence of S9.
      In contrast BPT sulfoxide and BPT-3,4-diol (a precursor to the bay-region diol
      epoxide of BPT) showed significant mutagenic activity in the presence of S9.
      Surprisingly, BPT sulfoxide was nearly 3.3-fold more mutagenic than BPT-3,4-diol
      in the presence of S9. BPT sulfoxide also displayed intrinsic mutagenic activity,
      which was nearly 1.5-fold less than that displayed by BPT-3,4-diol in the
      presence of S9. In base specific tester strains, BPT sulfoxide was the most
      active metabolite in strains TA7002, TA7004, and TA7005 with S9 activation. In
      these strains, BPT-3,4-diol was 2- to 7-fold less mutagenic than BPT sulfoxide in
      the presence of S9. Only in strain TA7006, BPT-3,4-diol was four-fold more
      mutagenic than BPT sulfoxide. The fact that BPT sulfoxide is significantly more
      mutagenic than BPT-3,4-diol in S. typhimurium strain TA100 suggests that the
      formation of sulfoxide may be the principal pathway for the metabolic activation
      of BPT to mutagenic products. Based on the results from Tester Strain TA7005, it
      indicate that BPT and its most mutagenic metabolite BPT sulfoxide induce
      predominantly CG --> AT transversion, which is observed as the most frequent base
      substitution mutation of p53 tumor-suppressor gene in human lung cancer.

PMID- 14698414
TI  - Genetic and metabolic effects of gluconasturtiin, a glucosinolate derived from
      cruciferae.
AB  - It is thought that induction of detoxifying phase-II drug metabolizing enzymes or
      inhibition of bioactivating phase-I by phytoalexins could protect against
      mutagens and neoplasia. In the search for potential naturally occurring molecular
      chemoprevention agents, particular attention has been devoted to isothiocyanates,
      which are breakdown products-via myrosinase-of glucosinolates such as
      gluconasturtiin (GNST), a natural constituent of cruciferae. Here, we first
      investigated the ability of GNST to modulate metabolizing enzymes in male Swiss
      Albino CD1 mice injected by gavage (24 mg/kg or 48 mg/kg b.w.) with GNST either
      in single or repeated (daily for four consecutive days) dose. Using selected
      probes to various cytochrome P450 (CYP) isoforms, a marked and generalized
      decrease of CYP content, NADPH-(CYP)-c-reductase and various CYP-linked
      monooxygenases (measuring CYP1A1, CYP2B1/2, CYP3A1/2, CYP1A2 and CYP2E1), was
      observed in hepatic, renal and pulmonary subcellular preparations (up to
      approximately 66% loss, liver). Similar behavior was recorded using the regio-
      and stereo-selective hydroxylation of testosterone as multibiomarker (CYP2A1 and
      CYP2B9, up to approximately 96% loss), as well as with the phase-II marker
      glutathione S-transferase (up to approximately 50% loss, liver). We also
      performed genotoxicity investigations, using the diploid D7 strain of yeast
      Saccharomyces cerevisiae as a biological test system. GNST was able to
      significantly induce point reverse mutation in growing cells without myrosinase,
      thus suggesting either a direct GNST or a CYP-linked metabolite role in the
      genotoxic response. On the contrary, in suspension test, the addition of
      myrosinase significantly increased mitotic gene conversion, probably due to the
      formation of GNST-derived phenylethyl isothiocyanate (PEITC) breakdown product.
      Taken together, our data suggest that GNST exerts a dual effect: while strongly
      inhibiting the microsomal (bioactivating) metabolism, GNST also possesses
      genotoxic activity. This concomitant mutagenic activity underlines the necessity
      of overall toxicological characterization of this (or any other molecule) prior
      to mass chemopreventive use.

PMID- 14698415
TI  - Biphasic effects of the flavonoids quercetin and naringenin on the metabolic
      activation of 2-amino-3,5-dimethylimidazo[4,5-f]quinoline by Salmonella
      typhimurium TA1538 co-expressing human cytochrome P450 1A2, NADPH-cytochrome P450
      reductase, and cytochrome b5.
AB  - Heterocyclic amines (HCAs) produced by cooking meat products at high temperatures
      are promutagens that are activated by cytochrome P450 (CYP) lA2. Using a newly
      developed Salmonella typhimurium TA1538/1A2bc-b5 strain, we tested the effect of
      quercetin and naringenin on the mutagenicity of 2-amino-3,4-dimethylimidazo[4,5
      f]quinoline (MeIQ). TA1538/1A2bc-b5 bears two plasmids, one expressing human
      CYP1A2 and NADPH-P450 reductase (NPR), and the other plasmid which expresses
      human cytochrome b5 (cyp b5). TA1538/1A2bc-b5 cells showed high activities of 7
      ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD)
      associated with CYP1A2 and are very sensitive to mutagenesis induced by several
      HCAs. MeIQ was found to be the strongest mutagen among the HCAs tested in this
      system. Mutagenicity of MeIQ was enhanced 50 and 42% by quercetin at 0.1 and 1
      microM, respectively, but suppressed 82 and 96% at 50 and 100 microM. Naringenin
      also increased the MeIQ-induced mutation about 37 and 22% at 0.1 and 1 microM,
      but suppressed it 32 and 63% at 50 and 100 microM concentrations, respectively,
      in TA 1538/1A2bc-b5 cells. Thus, they stimulated the MeIQ induced mutation at low
      concentrations, but strongly suppressed it at high concentrations. This biphasic
      effect of flavonoids was due to the stimulation or the inhibition of CYP1A2
      activity in a dose-dependent manner judging by the activities of EROD or MROD in
      the Salmonella cells. These results indicate that quercetin and naringenin can
      exhibit inhibitory or stimulating effects on CYP1A2 mediated mutagenesis by MeIQ,
      depending on their concentrations.

PMID- 14698416
TI  - DNA repair gene polymorphisms, pre-natal factors and the frequency of somatic
      mutations in the glycophorin-A gene among healthy newborns.
AB  - This study investigates variation in somatic mutation frequency, as measured by
      the glycophorin-A (GPA) somatic mutation assay, in relation to polymorphic
      variation among 435 newborn babies in DNA repair genes XRCC1, XRCC3 and XRCC4 and
      gender, parental age, social class and smoking habits. The three polymorphisms
      under investigation were an Arg --> Gln substitution at codon 399 in exon 10 of
      XRCC1, a Thr --> Met substitution at codon 241 in exon 7 of XRCC3 and an Ile -->
      Thr substitution at codon 401 in exon 4 of XRCC4. The study population is an
      extension of that previously analysed for GPA mutations and XRCC1 polymorphisms.
      A significant difference was seen in the earlier work in the genotype
      distribution for the XRCC1 Arg399Gln polymorphism between the main population and
      the small number with extreme values for NN variant frequency and this was
      maintained in the larger study group (OR 3.20 [95% CI: 1.16, 8.81]) P = 0.043).
      No such association was seen for XRCC3 or XRCC4 polymorphisms. When adjustments
      were made for multiple testing, neither N0 nor NN variant frequencies in the main
      study population were found to be influenced by the polymorphisms in XRCC1,
      XRCC3, or XRCC4. In addition, neither maternal or paternal smoking, age or social
      class nor the gender of the offspring were found to affect variant frequencies
      nor were variant frequencies influenced by any interaction between any of these
      factors and genotype. It is concluded that the genotypic variation in DNA repair
      genes examined in this study has no discernable effect on the genesis of the
      somatic mutations observed at birth.

PMID- 14698417
TI  - Female germ cell mutagenicity of model chemicals in Drosophila melanogaster:
      mechanistic information and analysis of repair systems.
AB  - In spite of differences between female and male germ cells, and although both of
      them contribute to the gene pool of future generations, most germ cell
      mutagenicity studies in higher eukaryotes have been carried out on males. To
      study the response of female germ cells to mutagen/carcinogen exposure, the
      mutagenicity of two model chemicals like diethyl sulfate (DES) and
      hexamethylphosphoramide (HMPA), and the monofunctional methylating
      chemotherapeutic drug streptozotocin (STZ), has been analysed on repair efficient
      females of Drosophila melanogaster. Results previously obtained with N-ethyl-N
      nitrosourea (ENU), another model chemical, have also been included in the
      analysis. The activity of bypass tolerance mechanism (BTM; represented by the
      mus308 locus) and nucleotide excision repair (NER) on the removal of oxygen and
      nitrogen ethylations was studied by determining DES mutagenicity in NER deficient
      females, comparing it with existing results for ENU, and by analysing both
      chemicals on BTM deficient females. Results indicate that (1) all chemicals are
      mutagenic on repair efficient females; (2) a measure of mutagenic activity ranked
      from the lowest DES to STZ, HMPA, and ENU as the highest. This order correlates
      with the repair of the respectively induced DNA damages, and with the mutagenic
      and carcinogenic potency of these compounds, considering the toxicity of cross
      linking agents; (3) NER efficiently repairs nitrogen ethylation damage and seems
      to contribute to the processing of oxygen damage in female germ cells; and (4)
      BTM is involved on the processing of oxygen ethylation damage, whereas the
      results on nitrogen ethylation are not clear. Finally, these results indicate
      that differences between male and female germ cells affect the response to
      chemical exposure, and therefore demonstrate the necessity of analysing also
      female cells in germinal mutagenicity studies. In addition, these studies can
      provide important mechanistic information about germ cell chemical mutagenesis,
      and even when the analysis of oogonia is not possible, since all female germ
      cells are pre-meiotic, studies of oocytes could be a model for pre-meiotic cells.

PMID- 14698418
TI  - Individual variation in microsatellite mutation rate in barn swallows.
AB  - The hypermutable nature of some microsatellite loci implies realistic
      possibilities for the large-scale detection of germline mutations by pedigree
      analysis. We have developed a model system for mutation analysis by the
      characterisation of patterns of mutation at three hypervariable microsatellites
      (two tetranucleotide and one pentanucleotide repeat loci) in barn swallows, all
      three markers having mutation rates at the percentage level. Here, we study how
      the mutation rate varies between individual birds of a Spanish population of barn
      swallows. A total of 53 mutations were identified from 2920 germline
      transmissions in 90 families with a total of 694 offspring. Mutations were not
      randomly distributed among individuals (P = 0.020). Attempts to correlate
      mutation rate with allele size, degree of inbreeding, immunocompetence and male
      age only revealed a strong effect of allele size. The mean mutation rate differed
      between colonies of breeding swallows which was probably due to a corresponding
      variation in allele size between colonies. There was no difference in the mean
      mutation rate between the Spanish and an Italian population. These results
      corroborate earlier findings, at the population level, of an allele size effect
      on the microsatellite mutation rate.

PMID- 14698419
TI  - Tests of induction in mice by acute and chronic ionizing radiation and
      ethylnitrosourea of dominant mutations that cause the more common skeletal
      anomalies.
AB  - Assessment-of-Dominant-Damage (ADD) experiments explored induction by proven
      specific-locus mutagens of dominant mutations that cause skeletal anomalies,
      cataracts, and stunted growth in offspring of mutagenized male mice. The data set
      reported here includes 6134 offspring. Mutagenic treatments included 600 R (i.e.,
      approximately 6 Gy) of X-rays delivered in about 7 min, 600 R of gamma rays
      delivered over about 110 days, and four weekly intraperitoneal (i.p.) injections
      of 77.5 mg/kg of ethylnitrosourea (ENU). The results reported in this paper are
      restricted to mutations induced in stem-cell spermatogonia and to the 34 more
      common skeletal anomalies (i.e., those found in 0.5% or more of the control
      offspring). Mutation induction was demonstrated for eight anomalies in the acute
      X-ray experiment and for 17 anomalies (including those same eight anomalies) in
      the ENU experiment. In spite of the surprisingly high mutation rates found for
      these treatments, there was no hint of any induction of such dominant mutations
      by 600 R of chronic gamma radiation. Our results suggest that several anomalies
      related to variation in the sacralization pattern may be particularly useful for
      revealing induction of dominant mutations.

PMID- 14698420
TI  - Description of first germinal mosaic mutation identified in dominant skeletal
      mutation experiments and considerations about how to deal with this kind of
      spontaneous mutation in analyses.
AB  - Germinal mosaicism is a well-established mechanism by which new spontaneous
      mutations enter the human population, but it is only rather recently that
      clusters of mutations arising in that way have been acknowledged and dealt with
      in specific-locus experiments on male mice. This paper reports the first cluster
      of germinal mosaic mutations to have been identified in experiments on the
      induction of dominant skeletal mutations. The mutation was detected in six
      offspring of a control male from the radiation part of an Assessment-of-Dominant
      Damage (ADD) experiment. Reasons are provided to explain why this one litter of
      six mutants was excluded from the analysis of induction of dominant mutations
      causing the more common skeletal anomalies, which is reported in another paper.
      The effects of excluding this litter from that analysis are fully described.
      There is discussion of why such clusters should be included in some analyses but
      omitted in others. They should certainly always be reported because, in some
      cases, they can have a major impact on conclusions. Details on this one cluster
      of FCGM mutations provide numerous examples of how a dominant skeletal mutation
      that causes rare effects can also cause many of the more common anomalies.

PMID- 14698421
TI  - Mutation rates in the complex microsatellite MYCL1 and related simple repeats in
      cultured human cells.
AB  - Microsatellite instability is a phenotype observed in tumors cells that have
      defects in DNA mismatch repair (MMR). Most markers used for detecting
      microsatellite instability are mono- and dinucleotide repeats, but one
      tetranucleotide repeat (MYCL1) has been reported to be useful for this purpose.
      The MYCL1 repeat is actually a complex repeat, made up of approximately 14 GAAA
      tetranucleotides plus various other GA-rich repeats. In order to determine the
      nature of the instability of the this sequence, we have used a frameshift
      reversion assay in MMR-proficient and -deficient human cells to compare the
      mutation rates and the types of mutation of MYCL1 to those of the related simple
      repeats (GAAA)17, (GA)17, and (CA)17. We found that the complex repeat was the
      most stable of the repeats examined in cells deficient in MMR; the
      tetranucleotide was less stable, while the dinucleotides were the least stable.
      In MMR-proficient cells, the relative rates were reversed; the MYCL1 repeat was
      the least stable, the tetranucleotide was more stable, and the dinucleotides were
      the most stable. These results suggest that MYCL1 and the pure tetranucleotide
      have relatively low rates of errors during replication, but that the errors in
      these repeats are corrected less efficiently than those in the smaller repeats.
      Because of their high rate of instability in MMR-proficient cells, MYCL1 and
      other tetranucleotide repeats appear to lack specificity for detection of tumors
      with defective MMR.

PMID- 14698422
TI  - Radio frequency radiation effects on protein kinase C activity in rats' brain.
AB  - The present work describes the effect of amplitude modulated radio frequency (rf)
      radiation (112 MHz amplitude-modulated at 16 Hz) on calcium-dependent protein
      kinase C (PKC) activity on developing rat brain. Thirty-five days old Wistar rats
      were used for this study. The rats were exposed 2 h per day for 35 days at a
      power density of 1.0 mW/cm2 (SAR = 1.48 W/kg). After exposure, rats were
      sacrificed and PKC was determined in whole brain, hippocampus and whole brain
      minus hippocampus separately. A significant decrease in the enzyme level was
      observed in the exposed group as compared to the sham exposed group. These
      results indicate that this type of radiation could affect membrane bound enzymes
      associated with cell signaling, proliferation and differentiation. This may also
      suggest an affect on the behavior of chronically exposed rats.

PMID- 14698423
TI  - Human gene variation: from SNPs to phenotypes.

PMID- 14698424
TI  - On the excess of G --> T transversions in the p53 gene in lung cancer cell lines.
      Reply to Pfeifer and Hainaut.
AB  - Our recent retrospective analysis of the lung cancer-associated p53 mutation data
      [Mutat. Res. 508 (2002) 1] showed the possibility of (i) inhibiting action of
      tobacco smoke on repair of G --> T primary lesions in the non-transcribed strand
      of the p53 gene and (ii) the origin of new p53 mutations, predominantly G --> T
      transversions, in lung cancer cell lines apparently unexposed to tobacco smoke.
      In summary, our arguments suggest that (i) in addition to polycyclic aromatic
      hydrocarbons (PAH)-DNA adducts there exist other lung cancer-specific, rather
      than smoke-specific sources of G --> T transversions and (ii) a direct mutagenic
      action is not the only smoke-associated cause of the prevalence of this class of
      p53 mutations in lung cancer. In the subsequent critical commentary [Mutat. Res.
      526 (2003) 39], Pfeifer and Hainaut suggested our arguments to be "incompatible
      with available evidence". We would like to address their critique, and appreciate
      the editors of Mutation Research giving us an opportunity to do so.

PMID- 14698427
TI  - Cholesterol is required for Leishmania donovani infection: implications in
      leishmaniasis.
AB  - Leishmania donovani is an obligate intracellular parasite that infects
      macrophages of the vertebrate host, resulting in visceral leishmaniasis in
      humans, which is usually fatal if untreated. The molecular mechanisms involved in
      host-parasite interaction leading to attachment on the cell surface and
      subsequent internalization of the parasite are poorly characterized. Cholesterol
      is a major constituent of eukaryotic membranes and plays a crucial role in
      cellular membrane organization, dynamics, function, and sorting. It is often
      found distributed non-randomly in domains in membranes. Recent observations
      suggest that cholesterol exerts many of its actions by maintaining a specialized
      type of membrane domain, termed "lipid rafts", in a functional state. Lipid rafts
      are enriched in cholesterol and sphingolipids, and have been thought to act as
      platforms through which signal transduction events are coordinated and pathogens
      gain entry to infect host cells. We report here that cholesterol depletion from
      macrophage plasma membranes using methyl-beta-cyclodextrin (MbetaCD) results in a
      significant reduction in the extent of leishmanial infection. Furthermore, the
      reduction in the ability of the parasite to infect host macrophages can be
      reversed upon replenishment of cell membrane cholesterol. Interestingly, these
      effects were not observed when parasites were serum-opsonized, indicating a
      specific requirement of cholesterol to mediate entry via the non-opsonic pathway.
      Importantly, we show that entry of Escherichia coli remains unaffected by
      cholesterol depletion. Our results therefore point to the specific requirement of
      plasma membrane cholesterol in efficient attachment and internalization of the
      parasite to macrophage cells leading to a productive infection. More importantly,
      these results are significant in developing novel therapeutic strategies to
      tackle leishmaniasis.

PMID- 14698428
TI  - Molecular cloning, expression and characterization of a serine proteinase
      inhibitor gene from Entamoeba histolytica.
AB  - Serine proteinase inhibitors (serpins) are irreversible suicide inhibitors of
      proteinases that regulate a wide range of biological processes, including
      pathogen evasion of the host defence system. We report the cloning and
      characterization of a gene encoding a serpin from the protozoan parasite
      Entamoeba histolytica (Ehserp) that may function in this manner. The protein
      encoded by Ehserp contains 371 amino acids with a predicted mass of 42.6 kDa.
      Antibodies to a 42 kDa recombinant Ehserp react specifically with two bands of 42
      and 49 kDa in trophozoite extracts. Ehserp has a cytoplasmic localization and is
      secreted by trophozoites incubated in the presence of mammalian cells, but not by
      resting trophozoites. A panel of mammalian serine proteinases was screened, but
      none of them was inhibited by the recombinant Ehserp. In contrast, the 49 kDa
      Ehserp present in the secretion product (SP) of activated macrophages interacted
      with human neutrophil cathepsin G to form a complex resistant to sodium dodecyl
      sulphate. We discuss the nature of the 42 and 49 kDa Ehserp and the possible
      roles that Ehserp may play in the survival of the parasite inside the host.

PMID- 14698429
TI  - An unusual mosaic structure of the PIM gene of Theileria parva and its
      relationship to allelic diversity.
AB  - Genetic diversity and structural organisation of the polymorphic immunodominant
      molecule (PIM) gene of the protozoan parasite Theileria parva was studied in
      isolates from sympatric and allopatric areas. The analyses revealed a mosaic
      structure consisting of highly conserved regions shared among some of the
      isolates from geographically different areas and homologous sequence runs shared
      among isolates from one area. The specific pattern of diversity in which large
      insertions and deletions were observed, giving a mosaic structure to the PIM
      locus, is quite exceptional for single-locus genes. The polymorphic middle region
      of the gene was characterised by large deletions or insertions in many isolates.
      There was no correlation between the copy number of the tetrapeptide repeats in
      this region and the total length of the sequence. The gene was highly polymorphic
      when compared with sequences from other known T. parva antigenic regions. The
      findings support the concept that as yet unidentified mechanisms are generating
      extensive diversity and shaping the PIM locus. The relevance of this finding for
      diagnosis and the relationship between these mechanisms and the possible role of
      this protein in host immune responses is discussed.

PMID- 14698430
TI  - Tests of cytoplasmic RNA interference (RNAi) and construction of a tetracycline
      inducible T7 promoter system in Trypanosoma cruzi.
AB  - The technique of RNA interference (RNAi) is exceedingly useful for knocking down
      the expression of a specific mRNA in African trypanosomes and other organisms for
      the purpose of examining the function of its gene. However, when we attempted to
      apply RNAi in the Latin American trypanosome, Trypanosoma cruzi, to diminish
      expression of mRNA encoding the surface protein amastin, we found that the
      amastin double-stranded RNA (dsRNA) was not efficiently degraded in either
      epimastigotes or amastigotes, and the level of amastin mRNA remained unchanged.
      We generated a strain of T. cruzi CL-Brener in which the T7 promoter and
      tetracycline operator could be used to maximize tetracycline-regulated dsRNA
      synthesis and constructed plasmids that direct dsRNA against four different T.
      cruzi endogenous genes (encoding beta-tubulin, GP72 (flagellar adhesion protein),
      ribosomal protein P0 and amastin) and an exogenously added gene (GFP; green
      fluorescent protein). After either stable or transient transfection of these
      plasmids into T. cruzi, the expected RNAi phenotype was not observed for any of
      the five genes, although the T. cruzi beta-tubulin RNAi plasmid did give the
      expected FAT cell phenotype in the African trypanosome, Trypanosoma brucei. These
      data indicate that, similar to Leishmania, T. cruzi lacks one or more components
      necessary for the RNAi pathway and that these components will need to be
      engineered into T. cruzi, or compensated for, before RNAi can be used to study
      gene function in this organism.

PMID- 14698431
TI  - Genes induced by a high-oxygen environment in Entamoeba histolytica.
AB  - Entamoeba histolytica, although a microaerophilic protozoan parasite, encounters
      a high-oxygen environment, during invasive amoebiasis. The parasite requires
      specific regulation of certain proteins to maintain its physiological functions
      to survive in the more oxygenated condition. Our endeavor was to know how does
      amoeba adapt itself in a high-oxygen environment. Reactive oxygen species (ROS)
      was found to accumulate in an increasing concentration within the stressed
      trophozoites in a time-dependent manner. Increased cytopathic activity was
      detected at 2h in high-oxygen-exposed E. histolytica lysate compared to lysate of
      normal E. histolytica trophozoites by Ussing chamber assay. The differential
      display and semi-quantitative polymerase chain reaction showed overexpression in
      the mRNA levels of thiol-dependent peroxidase (Eh29), superoxide dismutase (SOD),
      EhCP5, G protein, HSP70, and peptidylprolyl isomerase at different time periods
      of oxidative stressed trophozoites compared to normally cultured E. histolytica.
      Analyses of the up-regulated genes that are associated with stress response,
      viz., signal transduction, tissue destruction, and oxidative stress management,
      including enhanced expression of a 29-kDa Eh29, suggest that this organism has
      several protective mechanisms to deal with oxidative stress during invasion.

PMID- 14698432
TI  - The 6-phosphogluconate dehydrogenase from Trypanosoma cruzi: the absence of two
      inter-subunit salt bridges as a reason for enzyme instability.
AB  - The third enzyme of the pentose phosphate pathway (PPP), 6-phosphogluconate
      dehydrogenase (6PGDH), is present in the four major stages of Trypanosoma cruzi,
      CL Brener clone. The enzyme was too unstable to be purified from epimastigote
      cell-free extracts. Two genes encoding 6PGDH were cloned and sequenced; the
      predicted amino acid sequences differ only in five non-essential residues. Since
      Southern blots suggested the presence of a single copy per haploid genome, the
      two genes found are probably alleles. One of these genes, encoding a protein with
      78.6% identity with the Trypanosoma brucei 6PGDH, was expressed in Escherichia
      coli as an active recombinant enzyme, which was as unstable as the native 6PGDH.
      Modeling of the T. cruzi enzyme using the three-dimensional structure of the T.
      brucei 6PGDH as template suggested the lack of two out of five salt bridges
      proposed to strengthen subunit interactions in the active dimer. Restoring of
      these bridges by site-directed mutagenesis resulted in a more stable recombinant
      T. cruzi 6PGDH, which was used to determine the kinetic parameters. The K(m)
      value for 6-phosphogluconate (22.2+/-0.4 microM) was identical to the values
      reported for 6PGDHs from mammals, but the K(m) for NADP (5.9+/-0.2 microM) was
      significantly lower than the value reported for the human enzyme, and closer to
      that for the T. brucei enzyme. This suggests the possibility that inhibitors of
      the T. brucei 6PGDH, under development as potential drugs against African
      Trypanosomiasis, might also be successful for the chemotherapy of Chagas disease.

PMID- 14698433
TI  - An amino acid substitution in the Babesia bovis dihydrofolate reductase
      thymidylate synthase gene is correlated to cross-resistance against pyrimethamine
      and WR99210.
AB  - The genomic locus and cDNA encoding Babesia bovis dihydrofolate reductase
      thymidylate synthase (DHFR-TS) were cloned and sequenced. A single dhfr-ts gene,
      composed of four exons, encodes a 511 aa protein that is most closely related to
      Plasmodium falciparum DHFR-TS. The genomic locus is characterized by the presence
      of four other genes of which at least three are expressed during the erythrocytic
      cycle. Three of the genes were highly conserved in closely related Theileria
      species and for two of the genes and dhfr-ts, gene synteny was observed between
      B. bovis and Theileria parva, B. bovis in vitro cultures displaying approximately
      10-20-fold decreased sensitivity towards the antimalarial drugs WR99210 and
      pyrimethamine were selected repeatedly after prolonged growth in presence of
      drugs. Five cultures examined in detail were shown to encode a DHFR-TS carrying
      amino acid substitution S125F. Three-dimensional-modelling, using the P.
      falciparum DHFR structure as a template, suggests that substitution S125F
      protrudes into the binding site of NADPH. The S125F mutant could be isolated by
      growth under pyrimethamine or WR99210 pressure conferring cross-resistance to
      both drugs. Although opposing selection for pyrimethamine or WR99210 resistance
      was reported recently using P. falciparum or P. vivax strains carrying wildtype
      dhfr, the results obtained here are reminiscent of a quadruple mutant of P.
      falciparum dhfr displaying strong resistance to pyrimethamine and 10-fold
      enhanced resistance against WR99210. Wildtype B. bovis DHFR carries three
      mutations present in this mutant possibly explaining the low sensitivity to
      pyrimethamine and the ease by which moderately WR99210 resistant mutants could be
      isolated.

PMID- 14698434
TI  - Expression of Babesia equi EMA-1 and EMA-2 during merozoite developmental stages
      in erythrocyte and their interaction with erythrocytic membrane skeleton.
AB  - In the present study, we investigated the cellular localizations and expression
      patterns of equi merozoite antigens (EMA) -1 and -2 of Babesia equi during its
      asexual erythrocytic-developmental cycle using anti-EMA-1t or -2t mono-specific
      mouse serum. Indirect fluorescent antibody tests demonstrated that EMA-1 and EMA
      2 were not expressed in all the erythrocytic-developmental stages of the
      merozoites and that these two antigens were co-expressed during the early
      developmental stages. Additionally, it was shown that EMA-1 and EMA-2 were
      mutually expressed on the surface of extra-erythrocytic merozoites and also that
      the intra-erythrocytic merozoites shed only EMA-2 antigen in the infected
      erythrocytic cytoplasm or inside the membrane surface. The specific binding of
      EMA-2 to a Triton X-100-insoluble horse erythrocyte membrane fraction was also
      demonstrated. These findings facilitate our understanding of the biological roles
      of merozoite surface proteins of B. equi and our investigation for new drug
      targets.

PMID- 14698436
TI  - Ectopic expression of a Haemonchus contortus GATA transcription factor in
      Caenorhabditis elegans reveals conserved function in spite of extensive sequence
      divergence.
AB  - Comparative analysis between Caenorhabditis elegans and other nematode species
      offers a powerful approach to study gene function. C. elegans also has great
      potential as a surrogate expression system to study the function of genes from
      parasitic nematode species where transgenic methodologies are unavailable.
      However there is little information on the extent to which the biology of C.
      elegans is conserved with other nematode species and very few parasitic nematode
      genes have yet been functionally expressed in C. elegans. We have identified and
      characterised a homologue of the C. elegans GATA transcription factor elt-2, a
      central regulator of endoderm development, from the parasitic nematode Haemonchus
      contortus. The H. contortus ELT-2 polypeptide is present in endoderm nuclei
      throughout embryonic and post-embryonic development, except for in the infective
      L3 stage, and our experiments reveal that the development of the H. contortus
      endodermal lineage is strikingly similar to that of C. elegans. Sequence
      conservation between the H. contortus and C. elegans ELT-2 polypeptides broadly
      reflects function since the major region of sequence identity corresponds to the
      DNA binding domain. However, the overall level of sequence identity is remarkably
      low with the only other major region of identity corresponding to an unusual zinc
      finger domain. In spite of this, ectopic expression of the H. contortus elt-2
      gene in transgenic C. elegans is sufficient to activate a programme of endodermal
      differentiation demonstrating that function is highly conserved. This approach of
      ectopic expression using an inducible promoter provides an effective way in which
      to use C. elegans for the in vivo functional analysis of parasitic nematode
      genes.

PMID- 14698435
TI  - Trypanosome apoptotic factor mediates apoptosis in human brain vascular
      endothelial cells.
AB  - Human African trypanosomiasis (HAT, sleeping sickness) is a devastating disease
      caused by infection with Trypanosoma brucei ssp. These hemoflagellates invade the
      central nervous system (CNS) and induce meningo-encephalitis, neuronal
      demyelination, blood-brain-barrier (BBB) dysfunction, peri-vascular infiltration,
      astrocytosis and apoptosis. The molecular basis of these manifestations is
      unclear. We previously reported T. brucei-induced apoptosis in cerebella and
      brain-stem nuclei in mice at peak parasitemia. Here, we identify and characterize
      a trypanosome apoptotic factor (TAF) expressed by T. brucei that mediates
      apoptosis in mouse-brain and human-brain vascular endothelial cells (HBVEC).
      Molecular, biochemical and apoptotic assays, coupled with surface enhanced laser
      desorption ionization (SELDI), and protein database analyses were utilized to
      show that TAF is a soluble, non-serum, parasite-derived, heat-labile protein that
      causes DNA laddering and apoptosis in HBVEC. Protein-chip assay analysis of the
      SELDI spectrum of infected mouse serum and procyclic culture supernatants
      revealed a single major peak at 8652.7 Da. Further database analysis indicated
      that the TAF may be a procyclin or procyclin derivative. A synthetic 27 mer
      peptide (ProEP2-1), corresponding to a region common to EP procyclins (EP2-1),
      induced apoptosis in HBVEC and in cerebella of mice similar to that induced in T.
      brucei-infected mice. Western blot analysis utilizing an anti-procyclin
      monoclonal antibody (mAb) revealed that TAF is present in infected but not
      uninfected brain tissue lysates. Furthermore, this mAb blocked T. brucei- and
      ProEP2-1-induced apoptosis in HBVEC in vitro. We conclude that T. brucei TAF or
      its derivative(s) play a major role in the apoptosis associated with HAT
      pathology.

PMID- 14698437
TI  - Molecular analysis of the cytoadherence phenotype of a Plasmodium falciparum
      field isolate that binds intercellular adhesion molecule-1.
AB  - The ability of Plasmodium falciparum-infected erythrocytes to adhere to
      endothelial receptors and sequester in diverse host organs is an important
      pathogenic mechanism. Cytoadherence is mediated by variant surface antigens,
      which are referred to as PfEMP-1 and are encoded by var genes. The extracellular
      regions of PfEMP-1 contain multiple conserved cysteine-rich domains that are
      referred to as Duffy-binding-like (DBL) domains. Here, we analyze the adhesive
      phenotype of an Indian P. falciparum field isolate, JDP8, which binds ICAM-1 but
      does not bind CD36. This is a unique cytoadherence phenotype because P.
      falciparum strains that bind ICAM-1 described thus far usually also bind CD36.
      Moreover, binding to both receptors is thought to be important for static
      adhesion under flow. The ICAM-1 binding population of P. falciparum JDP8 adheres
      to endothelial cells under flow despite poor binding to CD36. We have also
      identified an expressed var gene, JDP8Icvar, which mediates the ICAM-1 binding
      phenotype of JDP8. Expression of different regions of JDP8Icvar on the surface of
      COS-7 cells followed by binding assays demonstrates that the ICAM-1 binding
      domain maps to the DBL2betaC2 domain of JDP8Icvar. Sequence comparison with two
      previously identified ICAM-1 binding domains of PfEMP-1, which also map to
      DBLbetaC2 domains, suggests that diverse P. falciparum isolates use a
      structurally conserved domain to bind ICAM-1. It thus appears that functional
      constraints may place limits on the extent of sequence diversity in receptor
      binding domains of PfEMP-1.

PMID- 14698438
TI  - High throughput immuno-screening of cDNA expression libraries produced by in
      vitro recombination; exploring the Plasmodium falciparum proteome.
AB  - Improved Plasmodium falciparum cDNA expression libraries were constructed by
      combining mRNA oligo-capping with in vitro recombination and directional cloning
      of cDNA inserts into a plasmid vector that expresses sequences as thioredoxin
      fusion proteins. A novel procedure has also been developed for the rapid
      identification of seropositive clones on high-density filters, using direct
      labelling of P. falciparum immune immunoglobulin with fluorescein isothiocynate
      (FITC). This approach combines the advantages of recombination-assisted cDNA
      cloning with high throughput, non-radioactive serological screening of expression
      libraries. Production of replicate colony matrices allows the identification of
      antigens recognised by different pools with different specificities from
      residents of a malaria endemic region. Analyses of DNA sequences derived from
      sero-reactive colonies indicate that this is an effective method for producing
      recombinant proteins that react with antibodies from malaria-exposed individuals.
      This approach permits the systematic construction of a database of antigenic
      proteins recognised by sera from malaria-exposed individuals.

PMID- 14698439
TI  - Functional analysis of Plasmodium falciparum parasitophorous vacuole membrane
      protein (Pfs16) during gametocytogenesis and gametogenesis by targeted gene
      disruption.
AB  - Gametocytogenesis is a tightly regulated process marked by differentiation
      through distinct morphological forms and coordinated expression of sexual stage
      gene products. The earliest known gene product expressed at the onset of
      Plasmodium falciparum gametocytogenesis is Pfs16 localized on the parasitophorous
      vacuole membrane (PVM). Targeted gene disruption was undertaken to disrupt
      expression of Pfs16 and examine its potential role during sexual development.
      Three independent clones were demonstrated to have the coding sequence of Ps16
      gene disrupted by the targeting plasmid by homologous recombination. No full
      length transcripts and PVM localized 16 kDa protein were detected. Instead, all
      three "16ko" clones expressed a protein of 14 kDa recognized by Pfs16 specific
      antibodies that was mislocalized to an unidentified double membrane compartment
      in the parasites. Disruption of Pfs16 gene resulted in a significant reduction in
      gametocyte production, although the small number of gametocytes produced appeared
      to be normal by molecular and phenotypic evidences. Preliminary observation also
      suggested impaired ability of male gametocytes to exflagellate in vitro. Pfs16
      does not appear to be essential for sexual development, instead may be required
      for optimal production of sexual parasites. Understanding mechanisms involved in
      the development of sexual stages of P. falciparum may identify novel targets for
      drugs and vaccines effective in reducing malaria transmission.

PMID- 14698440
TI  - Rapid evolution of an erythrocyte invasion gene family: the Plasmodium reichenowi
      Reticulocyte Binding Like (RBL) genes.
AB  - Malarial merozoites use an array of ligands, including members of the
      Reticulocyte Binding Like (RBL) super-family of invasion proteins, to identify
      and invade erythrocytes. RBL family members are large Type I membrane anchored
      proteins expressed at the invasive end of merozoites that share homology with the
      Reticulocyte Binding Proteins 1 and 2 (PvRBP1 and 2) of Plasmodium vivax.
      Plasmodium species vary widely both in the number and sequence of their RBL
      genes, with the recently completed Plasmodium falciparum genome containing five
      RBL genes. Of these, three encode proteins shown to be involved in erythrocyte
      invasion, a fourth is a pseudogene, and the role of the fifth is as yet unclear.
      In order to identify sequence similarities and differences that may have
      functional implications for erythrocyte invasion as well as to gain insights into
      the recent evolutionary history of the P. falciparum RBL genes, we have sequenced
      all five corresponding RBL genes from the chimpanzee parasite Plasmodium
      reichenowi, which is the closest phylogenetic relative of P. falciparum, yet is
      unable to invade human erythrocytes. Two of the five P. falciparum RBL genes have
      highly conserved complete open reading frames in both species, while the other
      three genes show evidence of gene conversion and rapid evolution. The RBL super
      family, therefore, appears to be surprisingly dynamic and divergent, implying
      that it is involved in species-specific aspects of erythrocyte recognition and
      invasion.

PMID- 14698441
TI  - A zinc-binding dual-specificity YVH1 phosphatase in the malaria parasite,
      Plasmodium falciparum, and its interaction with the nuclear protein, pescadillo.
AB  - Biochemical evidence revealed protein tyrosine kinase and phosphatase activities
      in the human malarial parasite Plasmodium falciparum, a member of the
      Apicomplexa. A novel cDNA sequence of a dual-specificity phosphatase was
      identified in both sexual and asexual stages of P. falciparum, and named PfYVH1,
      since the predicted primary structure of the 278-amino acid polypeptide showed
      significant similarity to the human and yeast YVH1 phosphatases. The N-terminal
      half of PfYVH1 contained a conserved tyrosine phosphatase catalytic domain within
      a dual-specificity phosphatase domain. The C-terminal region, consisting of one
      histidine and eight cysteines, represented a zinc-binding domain with a
      potentially unconventional architecture. Recombinant PfYVH1 contained 2mol of
      zinc per mol protein and dephosphorylated both phosphoserine and phosphotyrosine
      residues. Mutation of specific Cys residues in the putative zinc finger region
      abolished zinc binding and drastically reduced phosphatase activity, suggesting
      an allosteric role of zinc in catalysis. PfYVH1 was expressed in essentially all
      erythrocytic stages of the parasite, and shuttled between the nucleus and the
      cytoplasm in a stage-specific manner. A Plasmodium ortholog of the nuclear
      pescadillo protein (PfPES) was also characterized and shown to interact with
      PfYVH1, thus implicating PfYVH1 in the regulation of parasitic development.
      PfYVH1 represents the first dual-specificity zinc-finger phosphatase
      characterized in the protozoan kingdom.

PMID- 14698442
TI  - Regulation of carbohydrate metabolism in Ascaris suum body wall muscle: a role
      for the FMRFamide AF2, not serotonin.

PMID- 14698443
TI  - Furosemide analogues as potent inhibitors of the new permeability pathways of
      Plasmodium falciparum-infected human erythrocytes.

PMID- 14698444
TI  - Anticoagulant peptides from Ancylostoma caninum are immunologically distinct and
      localize to separate structures within the adult hookworm.

PMID- 14698445
TI  - Substance P immunoreactive nerve fibres in the domestic chick ankle joint before
      and after acute urate arthritis.
AB  - Substance P immunoreactive (SP-IR) nerve fibres were identified using
      fluorescence immunohistochemistry and the length of the labelled individual nerve
      fibres was measured using confocal microscopy of whole mounts of the lateral wall
      of the ankle joint in 2-week-old domestic chicks. In the normal ankle there was
      an extensive network of SP-IR fibres in the synovial and subsynovial tissue of
      the joint capsule. Fours hours after injection of sodium urate into the joint
      space the joint was inflamed and there was a significant reduction in the
      labelled nerve fibres. These results demonstrate experimentally that painful
      gouty arthritis produces a neurogenic depletion of substance P from peripheral
      nerve fibres in the synovial and subsynovial tissue.

PMID- 14698446
TI  - Intracranial measurement of current densities induced by transcranial magnetic
      stimulation in the human brain.
AB  - Transcranial magnetic stimulation (TMS) is a non-invasive technique that uses the
      principle of electromagnetic induction to generate currents in the brain via
      pulsed magnetic fields. The magnitude of such induced currents is unknown. In
      this study we measured the TMS induced current densities in a patient with
      implanted depth electrodes for epilepsy monitoring. A maximum current density of
      12 microA/cm2 was recorded at a depth of 1 cm from scalp surface with the optimum
      stimulation orientation used in the experiment and an intensity of 7% of the
      maximal stimulator output. During TMS we recorded relative current variations
      under different stimulating coil orientations and at different points in the
      subject's brain. The results were in accordance with current theoretical models.
      The induced currents decayed with distance form the coil and varied with
      alterations in coil orientations. These results provide novel insight into the
      physical and neurophysiological processes of TMS.

PMID- 14698448
TI  - Alpha-synuclein immunoreactivity in neuronal nuclear inclusions and neurites in
      multiple system atrophy.
AB  - We examined neuronal and oligodendroglial nuclear inclusions and neurites in the
      pontine base of multiple system atrophy brains using an antibody to alpha
      synuclein. Immunohistochemistry showed alpha-synuclein positive inclusions in the
      nuclei of some neurons and oligodendroglia. Immunoelectron microscopy showed that
      the labeled inclusions were composed of bundles of tightly packed straight
      filaments with a diameter of 10-20 nm. The filaments were similar, if not
      identical, in morphology and immunoreactivity, to those found in the soma of
      neurons and oligodendrocytes with glial cytoplasmic inclusions. In addition,
      similar immuno-positive filaments were found in dendrites or unmyelinated axons,
      but not in myelinated axons. The functional significance of these inclusions in
      terms of transcriptional and axonal dysfunction is unknown.

PMID- 14698447
TI  - Hypoxia-induced apoptosis of dorsal root ganglion neurons is associated with DNA
      damage recognition and cell cycle disruption in rats.
AB  - The metabolic effects of hyperglycemia and hypoxia are important in the
      pathogenesis of diabetic neuropathy. We demonstrated apoptosis in dorsal root
      ganglion neurons in vitro by employing an oxygen-glucose deprivation model that
      uses dorsal root ganglia incubated in room air (pO2=150 torr) followed by hypoxic
      conditions (pO2=7.6 torr). Apoptosis was confirmed by demonstrating caspase-3
      activation by immunocytochemistry. Immunocytochemistry and western blot analysis
      demonstrated an increase in activated p53, suggesting that DNA damage was
      occurring. Cell cycle disruption was examined by cyclin D1 expression. Neuronal
      death was associated with up-regulation of markers associated with DNA damage and
      aberrant entry into G1 of the cell cycle.

PMID- 14698449
TI  - A polymorphism in the angiotensin 1-converting enzyme gene is associated with
      damage to cerebral cortical white matter in Alzheimer's disease.
AB  - The impact of the insertion (I)/deletion (D) (I/D) polymorphism in the
      angiotensin 1-converting enzyme (ACE) gene on the extent of white matter myelin
      loss (ML) was investigated in four regions of the cerebral cortex in an autopsy
      confirmed series of 93 patients with Alzheimer's disease (AD). The possible
      influence of APO E epsilon4 allele acting in concert with ACE D allele was
      assessed. The extent of ML did not differ between D/D, I/D and I/I genotype
      groups when data from all four brain regions were combined. However, separate
      analysis showed that the frontal and temporal cortex tended to be affected more
      severely by ML in patients with D/D genotype compared to those with I/D and I/I
      genotypes. Stratification according to APO E epsilon4 allele revealed a greater
      overall ML in patients bearing at least one copy of ACE D allele and one APO E
      epsilon4 allele, especially in individuals homozygous for both. The APO E
      epsilon4 allele may therefore act synergistically in patients with AD (and other
      subjects) bearing ACE D/D genotype to increase the risk of ML, perhaps through
      transient ischaemic episodes consequent upon poor cardiac output associated with
      coronary atherosclerosis in patients with the APO E epsilon4 allele.

PMID- 14698450
TI  - Lovastatin and mevastatin reduce basal and cytokine-stimulated production of
      prostaglandins from rat microglial cells in vitro: evidence for a mechanism
      unrelated to the inhibition of hydroxy-methyl-glutaryl CoA reductase.
AB  - Statins were recently shown to possess anti-inflammatory activities, which might
      be responsible for their favourable effects in cardiovascular or CNS disorders
      independently from the inhibition of hydroxy-methyl-glutaryl CoA reductase. Here
      we investigated the effects of the statins lovastatin and mevastatin on
      prostanoid production in primary cultures of rat cortical microglia and
      astrocytes. We found that both statins significantly reduce prostaglandin E2
      (PGE2) release from microglia, either under basal conditions or after stimulation
      by interleukin-1beta. Lovastatin also tends to reduce, although not in a
      significant manner, basal and interleukin-1beta-stimulated PGE2 release from
      astrocytes. Precursors and intermediates in cholesterol biosynthesis--mevalonic
      acid and geranyl and farnesyl pyrophosphate--also reduce PGE2 production, and
      potentiate the inhibitory effects of statins, suggesting that the latter might
      not depend on the inhibition of hydroxy-methyl-glutaryl CoA reductase.

PMID- 14698451
TI  - EEG power and coherence analysis of visually presented nouns and verbs reveals
      left frontal processing differences.
AB  - Spectral power and coherence of the electroencephalogram was measured while
      subjects read either a verb or a noun which initiated a short meaningful phrase.
      For both types of words theta-power decreased substantially relative to a
      prestimulus baseline at left anterior electrode sites. All other frequency bands
      showed less (alpha, beta) or no effects at all (gamma). The theta-power
      attenuation was more pronounced for verbs than for nouns, thus indicating a
      stronger desynchronization for verbs at left frontal sites. Coherence of the
      theta-band revealed that these left anterior electrodes became decoupled from
      left and right posterior sites, again more for verbs than for nouns. These
      spectral changes are assumed to reflect processing differences due to the
      grammatical status of the two word categories.

PMID- 14698452
TI  - Perception of apparent motion in depth: a high-density electrical mapping study
      in humans.
AB  - We evaluated brain activity using 64-channel visual evoked potentials (VEPs)
      while subjects perceived apparent motion in depth. Checkerboard patterns (CBPs)
      within small and large circles were presented in turn as experimental conditions.
      Motion in depth was perceived when the CBP in the large circle was coarser than
      in the small circle; when coarseness did not change, no motion in depth was
      perceived. As control conditions only fine or coarse CBPs were presented. We used
      ANOVA to compare VEPs associated with experimental vs. control conditions and
      with coarse vs. fine CBPs. Negative potentials at a latency near 190 ms showed
      statistically significant interactions between these comparisons in the right
      lateral occipital and posterior parietal areas when apparent motion in depth was
      perceived. This suggests that higher tiers of the dorsal stream mediate this
      motion perception.

PMID- 14698453
TI  - Decrease in haemoglobin oxygenation during absence seizures in adult humans.
AB  - Near-infrared spectroscopy (NIRS) is a noninvasive method that allows the
      assessment of activation-induced cortical oxygenation changes in humans. It has
      been demonstrated that an increase in oxygenated and a decrease in deoxygenated
      haemoglobin can be expected over an area activated by functional stimulation.
      Likewise, an inverse oxygenation pattern has been shown to be associated with
      cortical deactivation. The aim of the current study was to determine the
      oxygenation changes that occur during absence seizures. We performed ictal NIRS
      simultaneously with video-EEG telemetry in three adult patients with typical
      absence seizures. NIRS probes were placed over the frontal cortex below the F1/F2
      leads. During all absence seizures studied, pronounced changes in cerebral Hb
      oxygenation were noted and there were no changes in the interval. We observed a
      reproducible decrease in [oxy-Hb] and an increase in [deoxy-Hb] during absence
      seizures indicating a reduction of cortical activity. Oxygenation changes started
      several seconds after the EEG-defined absence onset and outlasted the clinically
      defined event by 20-30 s.

PMID- 14698454
TI  - Theta coupling in the human electroencephalogram during a working memory task.
AB  - The role of coupling between prefrontal and temporo-parietal brain areas within
      the theta frequency range of the human electroencephalogram was explored in a
      working memory task. During encoding of visual information higher theta
      amplitudes were observed in the right compared to the left hemisphere. Retrieval
      of visuospatial and verbal information elicited a more bilateral activation
      pattern. These effects were accompanied by theta coupling between dorsolateral
      prefrontal and right posterior temporal electrode sites during encoding. During
      retrieval prefrontal and bilateral temporo-parietal brain areas were coupled.
      These results support the idea of working memory functions being dependent on
      distributed prefrontal-temporal networks.

PMID- 14698455
TI  - Differences in calcium signalling in rat peripheral sensory neurons.
AB  - Calcium influx and the resulting increase in intracellular calcium concentration
      [Ca2+]i can induce enhanced sensitivity to temperature increases in nociceptive
      neurons. Using the patch-clamp technique and simultaneous calcium
      microfluorimetry we show that experimental elevation of [Ca2+]i using the calcium
      ionophore ionomycin resulted in a significant potentiation of heat-activated
      currents. This was not the case when rises in [Ca2+]i were elicited by
      depolarization of the cell membrane by current injection via the patch pipette.
      Our data provide first, however, indirect evidence that in sensory neurons
      calcium ions may be guided into different intracellular microdomains depending on
      the type of ion channel or pore through which they enter the cell. We conclude
      that the compartmentalization of sensory neurons for calcium ions may be decisive
      on further signalling cascades accounting, for example, for neuronal plasticity.

PMID- 14698456
TI  - Alteration of striatal dopaminergic function induced by glioma development: a
      microdialysis and immunohistological study in the rat striatum.
AB  - Tumoral growth effects on brain circuitry and neurochemical activities remain
      poorly documented. This study evaluates C6 graft effects on striatal dopaminergic
      afferent projections at both anatomical and functional levels.
      Immunohistochemistry was performed to investigate changes in neurofilament (NF),
      tyrosine hydroxylase (TH) and dopamine transporter (DAT) expression. Dopaminergic
      turnover was assessed using multiprobe microdialysis in freely-moving rat. In C6
      graft striatum, dopamine (DA) catabolites were reduced in glioblastoma (DOPAC: 
      61%, HVA: -62%). In contrast, the DA level remained unchanged. Staining for NF,
      TH and DAT was drastically decreased inside the tumor. Our histological data
      report that striatal tumoral growth is associated with a decrease in the density
      of dopaminergic endings which can explain, at least in part, the decrease in DA
      turnover. The decrease in DAT transporter expression and the lack of change in DA
      level may result from an increase in DA diffusion from the peripheral areas of
      the tumor. In conclusion, glioblastoma growth has major consequences on the local
      neuronal circuitry and its neurochemistry. Changes in inter-connections and
      neurotransmitter turnover may result in abnormal neuronal firing activity and
      participate in clinical disorders associated with glioblastoma diagnosis.

PMID- 14698457
TI  - Diversity of the muscarinic and nicotinic responses of subfornical organ neurons
      in rat slice preparations.
AB  - Recently we found that subfornical organ (SFO) neurons were activated through
      nicotinic receptors as well as muscarinc. In this study, the preferential
      responses of single SFO neurons to both muscarine and nicotine were examined by
      using rat slice preparations, and current and voltage clamp recordings. When the
      amplitudes of the depolarizations and inward currents by muscarine and nicotine
      in single SFO neurons were compared, some neurons showed a higher sensitivity to
      muscarine than to nicotine while others showed vice versa. These data indicate
      that acetylcholine activates SFO neurons preferentially through either muscarinic
      or nicotinic receptors and suggest a diversity of cholinergic responses in the
      SFO.

PMID- 14698458
TI  - Distinct regions of periaqueductal gray (PAG) are involved in freezing behavior
      in hooded PVG rats on the cat-freezing test apparatus.
AB  - The periaqueductal gray (PAG) is considered to be an exit relay for defensive
      responses. Studies have shown that the ventrolateral periaqueductal gray (vlPAG)
      plays a role in the expression of freezing behavior whereas dorsolateral
      periaqueductal gray (dlPAG) is involved on both freezing and active forms of
      defensive behaviors. To further elucidate this theory, lesioned vlPAG and dlPAG
      rats were exposed to a cat in the cat-freezing test apparatus. Subsequently, a 7
      day repeated exposure to a cat was done on the vlPAG and dlPAG lesioned rats.
      Results showed that the vlPAG lesioned rats demonstrated significant decrease in
      freezing behavior and corresponding increase in locomotor activity, while the
      dlPAG lesioned rats failed to show any significance. Subsequent repeated exposure
      of the vlPAG lesioned rats to a cat for 7 days showed a gradual decrease in
      freezing behavior with significance shown at days 5, 6 and 7 while the dlPAG
      lesioned rats failed to show any changes. These results suggest that vlPAG
      regulates freezing behavior in hooded PVG rats.

PMID- 14698459
TI  - Activity-inducible protein Homer1a/Vesl-1S promotes redistribution of
      postsynaptic protein Homer1c/Vesl-1L in cultured rat hippocampal neurons.
AB  - In cultured rat hippocampal neurons, overexpression of Homer1a/Vesl-1S, an
      inducible protein upregulated by seizure or long-term potentiation, caused a
      reduction of punctate distribution of a postsynaptic protein Homer1c/Vesl-1L,
      without significant decrease in its total amount. Clusters of F-actin were also
      decreased. Treatments of cells with BDNF or a proteasome inhibitor, which cause
      increase in the expression level of endogenous Homer1a, also resulted in the
      reduction of Homer1c puncta. These results indicate that the accumulation of
      Homer1a, either exogenously expressed or endogenously induced, caused
      redistribution and dispersion of postsynaptic clusters of Homer1c and F-actin,
      suggesting an important role of Homer1a in synaptic remodeling.

PMID- 14698460
TI  - Increased phosphorylated-mu-opioid receptor immunoreactivity in the mouse spinal
      cord following sciatic nerve ligation.
AB  - The present study was designed to determine whether a state of neuropathic pain
      induced by sciatic nerve ligation could alter phosphorylated-mu-opioid receptor
      like immunoreactivity in the superficial dorsal horn of the mouse spinal cord.
      Mice with sciatic nerve ligation exhibited a significant suppression of the
      morphine-induced antinociception. Under this condition, phosphorylated-mu-opioid
      receptor-like immunoreactivity was clearly increased on the ipsilateral side in
      the superficial laminae of the L5 lumbar spinal dorsal horn in nerve-ligated
      mice. These findings suggest that the phosphorylation of the mu-opioid receptor
      in the spinal cord under a neuropathic pain-like state may, at least in part,
      contribute to the reduction in the antinociceptive effect produced by morphine in
      the mouse.

PMID- 14698461
TI  - Agmatine reduces only peripheral-related behavioral signs, not the central signs,
      of morphine withdrawal in nNOS deficient transgenic mice.
AB  - Agmatine inhibits morphine tolerance/dependence and potentiates morphine
      analgesia. This study was designed to investigate whether neuronal nitric oxide
      mediates the actions of agmatine in morphine dependence by using mice lacking a
      functional form of this enzyme. Mice received agmatine just after the morphine
      pellet implantation for 3 days twice daily or single injection 30 min before
      naloxone. In both genotypes treated for 3 days with morphine pellets, naloxone
      administration precipitated clear signs of withdrawal. Both acute and chronic
      administration of agmatine reduced withdrawal signs in wild type mice and reduced
      only peripheral signs of morphine dependence in neuronal nitric oxide synthase
      knockout mice. Withdrawal signs, that are related to central nervous system
      activity were not affected. These findings indicate that neuronal nitric oxide
      synthase partly mediates the effects of agmatine in morphine physical dependence.

PMID- 14698462
TI  - Electroacupuncture reduces the extent of lipid peroxidation by increasing
      superoxide dismutase and glutathione peroxidase activities in ischemic-reperfused
      rat brains.
AB  - Reactive oxygen species can be scavenged by superoxide dismutase (SOD) and
      glutathione peroxidase (GPx). During ischemia-reperfusion, the normal functioning
      of these antioxidant enzymes may be insufficient for the prevention of oxidant
      induced peroxidation of membrane lipids and hence cerebral infarction. We
      therefore investigated whether electroacupuncture (EA) treatment at Fengchi
      points in post-ischemic rats could increase the antioxidant enzyme activities and
      thereby reduce the extent of lipid peroxidation. The results indicated that while
      EA did not alter the antioxidant enzyme activities in non-ischemic normal rat
      brains, ischemia-reperfusion caused significant increases in SOD and GPx
      activities. EA treatment further increased the antioxidant enzyme activities in
      ischemic-reperfused brain tissues, with a concomitant decrease in the extent of
      lipid peroxidation. Our finding suggests that EA treatment at Fengchi reduced the
      extent of lipid peroxidation in ischemic-reperfused rat brains, possibly by
      increasing the activities of SOD and GPx.

PMID- 14698463
TI  - Glutathione monoethyl ester provides neuroprotection in a rat model of stroke.
AB  - Oxidative stress plays an important role in the development of tissue damage
      following transient focal cerebral ischaemia. Glutathione is a central component
      in the antioxidant defence of cells. We have previously shown a close association
      between mitochondrial glutathione loss and cell death following middle cerebral
      artery (MCA) occlusion. Glutathione monoethyl ester increases cellular
      glutathione and is particularly effective in increasing the mitochondrial pool.
      In the present investigation, we infused glutathione monoethyl ester into the
      third ventricle during 2 h of MCA occlusion and 48 h of reperfusion. Infarct size
      was reduced from 46% of the total ischaemic hemisphere in saline-treated animals
      to 16% following ester treatment. Thus, glutathione monoethyl ester provides
      neuroprotection following transient focal cerebral ischaemia.

PMID- 14698464
TI  - Central administration of leucine, but not isoleucine and valine, stimulates
      feeding behavior in neonatal chicks.
AB  - Branched-chain amino acids (BCAAs) are essential amino acids that play a major
      role in brain energy metabolism. This study was done to elucidate whether central
      injection of BCAAs influences feeding behavior in chicks. We found that the
      intracerebroventricular injection of leucine (200 microg) significantly
      stimulated food intake in neonatal chicks during 30 min postinjection.
      Additionally, the starting time of feeding and pecking rhythm after injection
      were significantly accelerated by leucine. In contrast, isoleucine and valine had
      no effect on ingestive response during experiment periods. Moreover, a metabolite
      of leucine (alpha-ketoisocaproic acid) at an equimolar concentration of leucine
      also did not increase food intake in chicks. These results suggest that leucine
      induces hyperphagia of neonatal chicks and it may be due to the synthesized
      glutamate by exogenous leucine.

PMID- 14698465
TI  - Impulsive-like behavior in differential-reinforcement-of-low-rate 36 s responding
      in mice depends on training history.
AB  - Prior behavioral history in operant conditioning paradigms may induce impulsive
      like responding as shown in rats. Little is known to what extent behavioral
      history influences subsequent behavior in mice, therefore the present study
      investigated the effects of lever-pressing under a fixed-ratio 5 schedule of
      reinforcement on subsequent differential-reinforcement-of-low-rate (DRL) 36 s
      performance in wild type mice compared to the behavior of 5-HT1B receptor
      knockout mice. Acquisition of both autoshaping and fixed-ratio 5 training was
      faster in 5-HT1B receptor knockout compared to wild type mice. Nevertheless, in
      the DRL 36 s procedure no differences were observed between genotypes. Both wild
      type and 5-HT1B receptor knockout mice displayed premature or impulsive-like
      responding in the DRL 36 s procedure, for example a peak location of responses
      around 20 s and high rates of responding. Taken together, the present data
      suggest that impulsive-like responding in the DRL 36 s procedure in mice depends
      on prior behavioral history.

PMID- 14698466
TI  - Effects of experimentally induced inflammation on temporomandibular joint
      nociceptors in rats.
AB  - Response properties of nociceptors in the temporomandibular joint (TMJ) and
      surrounding area under experimental inflammation were investigated using an in
      vitro TMJ-nerve preparation in the rat. Nociceptive units (receptor and
      innervating nerve fiber) were classified into the following subtypes: Adelta-high
      threshold mechanonociceptor (HTM), Adelta-polymodal nociceptor (POLY), C-HTM and
      C-POLY. In the inflamed joint, mechanical thresholds tended to be lower; however,
      the reaction to bradykinin was not identified as clearly as in control.
      Experimentally induced inflammation increased the proportion of heat-sensitive
      units and lowered heat threshold significantly. These results suggest that
      inflammation may sensitize nociceptors in the temporomandibular joint, and cause
      hyperalgesia and allodynia.

PMID- 14698468
TI  - Serotonergic genes and personality traits in the Korean population.
AB  - Serotonergic genes have been implicated in mood disorders, alcoholism and certain
      personality traits. The goal of this study was to investigate the relationship
      between personality traits and several important genes in the serotonin system.
      The participants included 146 healthy adults with no history of psychiatric
      disorders or other physical illness during the last 6 months. All participants
      were tested by the Temperament and Character Inventory (TCI) and genotyped
      serotonin transporter, serotonin receptors (5-HT(2A) and 5-HT(6)) and tryptophan
      hydroxylase gene polymorphisms. Genotyping was analyzed with polymerase chain
      reaction. Differences in TCI dimensions and sub-scales among three groups were
      examined with ANOVA. Our result suggested that 5-HT(2A) receptor gene
      polymorphism (A-1438G) appears to be associated with self-determinism and self
      transcendence (ST). Our result also indicated a significant relationship between
      5-HT(6) receptor gene polymorphism (C267T) and ST. Further studies of
      polymorphisms of other genes and their interactions may clarify the complex
      relationship between personality and genes.

PMID- 14698469
TI  - Modafinil prevents the MPTP-induced increase in GABAA receptor binding in the
      internal globus pallidus of MPTP-treated common marmosets.
AB  - The psychostimulant drug modafinil induces a reversal of motor deficits in MPTP
      treated primates and prevents MPTP toxicity to substantia nigra but its mechanism
      of action is not clear. In common marmosets acutely treated with MPTP in the
      presence or absence of modafinil, we have studied changes in GABA(A) receptor
      binding in the basal ganglia. MPTP treatment had no effect on [(3)H]
      flunitrazepam (FNZ) binding density in the striatum or external globus pallidus
      (GPe) but increased [(3)H]-FNZ binding density in the internal globus pallidus
      (GPi). Administration of modafinil (10-100 mg/kg) with MPTP did not alter [(3)H]
      FNZ binding density in the striatum or GPe. Low doses of modafinil (10 and 30
      mg/kg) had no effect on the increased [(3)H]-FNZ binding density in the GPi but
      high dose modafinil (100 mg/kg) significantly decreased [(3)H]-FNZ binding
      density in GPi. These findings suggest that modafinil can selectively alter GABA
      binding density in the GPi either by preventing MPTP-induced toxicity or through
      an action on striatal output pathway related to its antiparkinsonian activity and
      its ability to inhibit MPTP toxicity.

PMID- 14698470
TI  - Increase of spiny I activity in striatum after development of context-dependent
      sensitization of catalepsy in rats.
AB  - In this study, it was investigated whether context-dependent sensitization of
      catalepsy changes the firing pattern in striatum. Rats were treated with either
      haloperidol (0.5 mg/kg i.p.) or saline, and tested on catalepsy with a
      concomitant single-unit measurement of the spiny I activity. Administration of
      haloperidol caused sensitization of catalepsy as measured on bar and grid.
      Concurrent within this behavioral change, spike-frequency increased over the
      course of the testing days in haloperidol-treated rats whereas the spike
      frequency remained unchanged in saline-treated animals. Burst-frequency remained
      unchanged within both treatment groups over the days. In conclusion,
      sensitization of catalepsy is represented by striatal cellular activity as
      indicated by increases in spike-frequency of spiny I neurons.

PMID- 14698471
TI  - Human non-phase-locked gamma oscillations in experience-based perception of
      visual scenes.
AB  - Perception results from ongoing interactions between stimulus-driven visual
      processes and cognitive context. These reciprocal relations are emphasized when a
      visual stimulus is degraded, forcing the perceiver to fill the missing
      information in, based on internal representations. The neural mechanisms by which
      internal representations facilitate visual perception are still unclear. Here we
      investigated the role of EEG oscillations in the gamma band, thought to reflect
      the elaboration of internal visual representations, in the experience-based
      perception of visual scenes. Twelve subjects were trained with degraded images of
      natural scenes. EEG was recorded while they performed a detection task on trained
      and untrained degraded stimuli. Non-phase-locked gamma band responses in a large
      frequency spectrum (55-85 Hz) were observed around 200 ms post-stimulus onset at
      posterior sites, and were larger when subjects reported an accurate perception
      based on previous experience. These results suggest that mid-latency gamma
      oscillations in the visual cortex underlie the experience-based perception of
      visual scenes.

PMID- 14698472
TI  - Visual completion of three-dimensional, chromatic, moving stimuli in humans.
AB  - We studied whether visual completion can be produced within three-dimensional (3
      D), moving, chromatic objects. Rotating thin and thick discs with red sectors,
      forming the corners of Kanizsa triangle, were presented on a display. Observers
      also rotated a hand-held real thin Kanizsa triangle. An illusory, moving contour
      encompassing an illusory colourful triangle was generally observed. This
      indicates that the visual system is capable of filling in complex (3-D, moving,
      chromatic) percepts.

PMID- 14698473
TI  - Persistence of visual-tactile enhancement in humans.
AB  - We report two experiments in which non-informative vision of the finger enhanced
      tactile acuity on the fingertip. The right index finger was passively lifted to
      contact a grating. Twelve participants judged orientations of tactile gratings
      while viewing either the fingertip, or a neutral object presented via a mirror at
      the fingertip's location. In Expt. 1, tactile orientation discrimination for near
      threshold gratings was improved when viewing the fingertip, compared to viewing
      the neutral object. Experiment 2 examined the temporal persistence of this
      effect, and found significant visual-tactile enhancement when a dark interval of
      up to 10 s intervened between viewing the finger and tactile stimulation. These
      results suggest that viewing the body modulates the neural circuitry of primary
      somatosensory cortex, outlasting visual inputs.

PMID- 14698474
TI  - Ketamine attenuates hypocapnia-induced neuronal damage in the caudoputamen in a
      rat model of chronic cerebral hypoperfusion.
AB  - We previously demonstrated that the caudoputamen was exclusively further damaged
      by hypocapnia in a rat with chronic cerebral hypoperfusion which is characterized
      by white matter lesions (WML) and a well-established model for patients with
      cerebrovascular diseases and/or dementia, and suggest that this process may be
      the cause of long lasting postoperative delirium or brain dysfunction in such
      patients. In the present study, we investigated whether ketamine, a non
      competitive N-methyl-D-aspartate receptor antagonist, could attenuate the
      neuronal damage in the caudoputamen. Ketamine, at doses of 10 and 20 mg/kg, which
      was given intraperitoneally before hypocapnia induction, attenuated the
      aggravation of WML score, neuronal damage, and astroglial proliferation in the
      rat caudoputamen. These results suggest that ketamine may be beneficial for
      preventing postoperative brain dysfunction, especially in patients with
      cerebrovascular diseases and/or dementia induced by hypocapnia, which is likely
      to occur in the mechanical ventilation used during surgery.

PMID- 14698475
TI  - Analgesic and behavioral effects of a 100 microT specific pulsed extremely low
      frequency magnetic field on control and morphine treated CF-1 mice.
AB  - Diverse studies have shown that magnetic fields can affect behavioral and
      physiological functions. Previously, we have shown that sinusoidal extremely low
      frequency magnetic fields and specific pulsed magnetic fields (Cnps) can produce
      alterations in the analgesia-related behavior of the land snail. Here, we have
      extended these studies to show an induction of analgesia in mice equivalent to a
      moderate dose of morphine (5 mg/kg), and the effect of both Cnp exposure and
      morphine injection on some open-field activity. Cnp exposure was found to prolong
      the response latency to a nociceptive thermal stimulus (hot plate). Cnp+morphine
      offset the increased movement activity found with morphine alone. These results
      suggest that pulsed magnetic fields can induce analgesic behavior in mice without
      the side effects often associated with opiates like morphine.

PMID- 14698476
TI  - alpha-Synuclein selectively increases manganese-induced viability loss in SK-N-MC
      neuroblastoma cells expressing the human dopamine transporter.
AB  - The established or potentially toxic agents implicated in the nigral cell death
      in Parkinson's disease, dopamine, 1-methyl-4-phenylpyridinium (MPP(+)), iron, and
      manganese, were examined as to their effects on the viability of cells
      overexpressing alpha-synuclein. SK-N-MC neuroblastoma cells stably expressing the
      human dopamine transporter were transfected with human alpha-synuclein and cell
      clones with and without alpha-synuclein immunoreactivity were obtained. Cells
      were exposed for 24-72 h to 1-10 microM dopamine, 0.1-3 microM MPP(+), 0.1-1 mM
      FeCl(2) or 30-300 microM MnCl(2) added to the culture medium. There was no
      difference between cells expressing alpha-synuclein and control cells after
      exposure to dopamine, MPP(+) or FeCl(2). However, MnCl(2) resulted in a
      significantly stronger decreased viability of cells overexpressing alpha
      synuclein after 72 h. These findings suggest that manganese may co-operate with
      alpha-synuclein in triggering neuronal cell death such as seen in manganese
      parkinsonism. The relevance of our observations for the pathoetiology of
      Parkinson's disease proper remains to be determined.

PMID- 14698477
TI  - An electrophysiological correlate of human visual awareness.
AB  - In order to shed more light on the neural correlates of human visual awareness,
      event-related potentials (ERPs) were recorded in a perceptual threshold
      experiment. The masked stimuli (line-drawings of coherent, familiar objects and
      scrambled, meaningless non-objects) were presented below, near, and above the
      subjective perceptual threshold. A prominent negative ERP deflection, peaking
      around 260-270 ms from stimulus onset, was observed only for the stimuli reaching
      subjective visual awareness. The results indicate a direct relationship between
      the crossing of the subjective threshold and this negative ERP deflection. A
      similar ERP response called 'visual awareness negativity' (VAN) has been observed
      in recent studies, using completely different stimulus manipulations (change
      blindness, reduced contrast stimuli). Hence, VAN appears to be a general
      electrophysiological correlate of visual awareness, observed in any experimental
      design that contrasts consciously perceived vs. unperceived visual stimuli.

PMID- 14698478
TI  - Neural networks engaged in short-term memory rehearsal are disrupted by
      irrelevant speech in human subjects.
AB  - Rehearsal mechanisms in human short-term memory are increasingly understood in
      the light of both behavioural and neuroanatomical findings. However, little is
      known about the cooperation of participating brain structures and how such
      cooperations are affected when memory performance is disrupted. In this paper we
      use EEG coherence as a measure of synchronization to investigate rehearsal
      processes and their disruption by irrelevant speech in a delayed serial recall
      paradigm. Fronto-central and fronto-parietal theta (4-7.5 Hz), beta (13-20 Hz),
      and gamma (35-47 Hz) synchronizations are shown to be involved in our short-term
      memory task. Moreover, the impairment in serial recall due to irrelevant speech
      was preceded by a reduction of gamma band coherence. Results suggest that the
      irrelevant speech effect has its neural basis in the disruption of left
      lateralized fronto-central networks. This stresses the importance of gamma band
      activity for short-term memory operations.

PMID- 14698479
TI  - Artificially produced meteorological changes aggravate pain in adjuvant-induced
      arthritic rats.
AB  - To examine the effects of change in meteorological parameters on pain-related
      behaviors in a simulated arthritic condition, rats with an injection of complete
      Freund's adjuvant into the tibio-tarsal joint were exposed to low barometric
      pressure (20 mmHg below the natural atmospheric pressure) and low ambient
      temperature (7 degrees C lower than 22 degrees C) in a climate-controlled room.
      When the arthritic rats were exposed to these environments, the already increased
      number of hindpaw withdrawals in response to noxious mechanical stimulation
      (hyperalgesia) was further increased, and a hindpaw withdrawal response to
      innocuous mechanical stimulation (allodynia) began to occur. Such exposures did
      not influence any of the pain-related behaviors of the control rats. These
      results show that lowering barometric pressure and ambient temperature within the
      range of natural environmental fluctuation intensify pain in arthritic rats.

PMID- 14698480
TI  - Evidence from brain imaging with fMRI supporting functional specificity of
      acupoints in humans.
AB  - We tested whether the stimulation of acupoints in the same spinal segments could
      induce different central responses with functional magnetic resonance imaging
      (fMRI) study. Stimulation of acupoints ST36/SP6 (Zusanli/Sanyinjiao) or GB34/BL57
      (Yanglingquan/Chengshan) both activated primary and secondary somatosensory area,
      insula, ventral thalamus, parietal Brodmann Area 40, temporal lobe, putamen, and
      cerebellum, while de-activated amygdala. Nevertheless, ST36/SP6 stimulation
      specifically activated orbital frontal cortex and de-activated hippocampus.
      Alternatively, stimulation of GB34/BL57 activated dorsal thalamus and inhibited
      those of primary motor area and premotor cortex. Thus, stimulation of acupoints
      in the same spinal segments induced distinct though overlapped cerebral response
      patterns, which indicated the existence of acupoint specificity.

PMID- 14698481
TI  - The effect of polyglutamine expansion in the human androgen receptor on its
      ability to suppress beta-catenin-Tcf/Lef dependent transcription.
AB  - Expansion of the polyglutamine repeat region of the androgen receptor (AR)
      results in Kennedy's disease, a neurological disorder typified by degeneration of
      motor neurons in the brain stem and spinal cord. As the AR has been shown to
      inhibit beta-catenin dependent (Wnt) signalling we asked if expansion of the
      polyglutamine repeats might affect this property of the protein. Using the
      TOPflash/FOPflash reporter assay we found that a pathogenic form of the AR
      containing 51 glutamine repeats showed a consistent, though minimal, reduction in
      its ability to inhibit beta-catenin-mediated transcription, in comparison to a
      non-pathogenic form with 20 repeats. A reduced ability to inhibit Wnt signalling
      may thus contribute in part to the underlying aetiology of Kennedy's disease.

PMID- 14698482
TI  - Rotenone induces disassembly of the Golgi apparatus in the rat dopaminergic
      neuroblastoma B65 cell line.
AB  - It has been reported that the Golgi apparatus (GA) is fragmented in some
      neurodegenerative diseases. However, the significance of the GA fragmentation or
      disassembly in neurodegeneration is still obscure. To clarify the involvement of
      this organelle in apoptosis of neuronal cells, we examined the morphological
      changes in the GA induced by rotenone, a pesticide that produces selective
      dopaminergic neurodegeneration. In dopaminergic neuroblastoma B65 cells, a 5-day
      rotenone treatment (50 nM) promoted cell damage. Rotenone-treated cells showed
      round nuclei, diffuse signals of the GA and cytosolic redistribution of
      cytochrome c. Nevertheless, these type of cells without nuclear fragmentation did
      not show any caspase-3 expression. These results indicate that rotenone induces
      disassembly of the GA in the early stages of the apoptotic process.

PMID- 14698483
TI  - Protective effect of growth hormone on neuronal apoptosis after hypoxia-ischemia
      in the neonatal rat brain.
AB  - Recent studies have shown that growth hormone (GH) can reduce neuronal loss after
      hypoxic-ischemic injury (HI) in neonatal and juvenile rat brains. Here, we
      investigated whether GH exerts its neuroprotective role through an anti-apoptotic
      effect in neonatal rat brains damaged by severe HI. Gross and histological
      observations showed that the extent of brain damage was found to be reduced in GH
      treated brain at E7 after injury. In a terminal transferase-mediated dUTP nick
      end-labeling (TUNEL) study, TUNEL-positive apoptotic cells were localized only at
      the damaged region in animals treated with saline, which was confirmed by an
      electron microscopy. In an immunohistochemical study with anti-bcl-2, -bax, -bad,
      -neuronal nitric oxide synthase (nNOS), -inducible NOS (iNOS) and -endothelial
      NOS (eNOS) antibodies, we observed that bax, bad, iNOS and eNOS were elevated in
      the saline-treated group. This study thus suggests that the protective role of GH
      against HI injury is mediated thorough an anti-apoptotic effect, which offers the
      possibility of a GH application for the treatment of neonatal HI encephalopathy.

PMID- 14698484
TI  - Target evaluation processing and serum levels of nerve tissue protein S100B in
      patients with remitted major depression.
AB  - Selective attention processes (N2 and P3 components of event-related potentials
      (ERPs)) have been shown to be impaired in depressed patients but findings have
      been mixed. Part of this variability might be explained by neurobiological
      factors. ERPs (Go/Nogo paradigm) were investigated in patients with remitted
      major depression in relation to S100B. S100B, an astroglial protein with
      neuroplastic properties, has been shown to be increased in depression. Its
      pathophysiologic role in depression, however, is not yet sufficiently understood.
      Patients with increased S100B serum levels (n=6) showed a normal N2- and P3
      amplitude in contrast to a reduced N2- and P3-amplitude in patients with normal
      S100B serum levels (n=6). These findings provide evidence of a correlation
      between S100B levels and attentional processes in patients with recurrent
      depression and further substantiate S100B's role as a marker in the course of
      affective disorders.

PMID- 14698485
TI  - Activation of cerebral cortex during acoustic challenge or acute foot-shock in
      freely moving, nontethered rats.
AB  - Most brain mapping techniques require immobilization of the subject, which
      extinguishes all but the simplest behaviors. We applied in freely moving rats an
      implantable microbolus infusion pump (MIP) which can be triggered by remote
      activation for the injection of the cerebral blood flow tracer
      [(14)C]iodoantipyrine during behavioral activation. Consistent with previous
      electrophysiological, metabolic and brain anatomic studies, CBF-related tissue
      radioactivity (CBF-TR) increased in acoustic cortex during a 1000 Hz/8000 Hz
      alternating tone. In response to an acute foot-shock, CBF-TR increased in visual
      cortex, parietal association cortex, and extended into primary motor cortex, and
      primary somatosensory cortex mapping the trunk. These results support the utility
      of implantable pumps as adjunct tools for studying cerebral activation during
      behavioral challenges in nontethered, nonrestrained animals.

PMID- 14698487
TI  - Involvement of the medial amygdaloid nucleus in restraint stress-induced pressor
      responses in rats.
AB  - Restraint stress increased the number of neurons with Fos immunoreactivity in the
      medial amygdaloid nucleus in rats and caused an increase in blood pressure. The
      stress-induced pressor response was inhibited by muscimol (80 pmol), a
      neuroinhibitory compound, injected bilaterally into the medial amygdaloid area,
      whereas muscimol (8 pmol) similarly injected had only a tendency of inhibition of
      the pressor response. These data suggest that the medial amygdaloid nucleus is
      involved in mediation of the restraint stress-induced pressor response.

PMID- 14698486
TI  - Hemorrhagic sympathoinhibition mediated through the periaqueductal gray in the
      rat.
AB  - In response to hemorrhage in the anesthetized rat, an initial renal
      sympathoexcitation is followed by profound sympathoinhibition and hypotension
      with increasing blood loss. Microinjection of the gamma-aminobutyric acid(A)
      agonist muscimol to block neurotransmission through the sympathoinhibitory region
      of the ventrolateral periaqueductal gray matter (vlPAG) did not alter resting
      sympathetic nerve activity or blood pressure. However, the response to hemorrhage
      was converted to a maintained renal sympathoexcitation with a delayed and
      attenuated accompanying hypotension. These data indicate that neurons in the
      vlPAG mediate the sympathetic and cardiovascular responses to severe hemorrhage.

PMID- 14698488
TI  - Effect of long-term care insurance on communication/recording tasks for in-home
      nursing care services.
AB  - The purpose of this research was to clarify the possible changes brought about by
      the introduction of the long-term care insurance system in terms of number of
      communication/recording tasks, related nursing services in use, and when and
      where these tasks were performed. By examining the detailed content of
      communication/recording tasks, this study also sought to explore the advantages
      of introducing information technology (IT) systems in nursing service settings.
      The study was designed before-and-after study in two sessions, February 2000 and
      August 2000, namely before and after the introduction of Japan's long-term care
      insurance system. Participants were clients using the institution's in-home
      nursing services and all staff in a medical institution located in the Mikawa
      region of Aichi Prefecture, Japan. Following measurements were performed: (1).
      nursing service in use, (2). type of job, (3). date and time, (4). from whom,
      (5). to whom, (6). communication tool and (7). content, related to a particular
      communication. Communication/recording tasks were frequently performed around the
      starting and closing time of services. Following the adoption of the new system,
      these tasks tended to occur mostly around the starting time of services. As for
      the staff, the involvement of the professional carers increased. Regarding
      content of communication/recording, reports, confirmation and instruction
      increased. In conclusion, the use of IT driven devices is recommended to
      streamline the performance of communication/recording tasks as well as to ease
      the rush of these tasks thereby improving the quality of nursing services.

PMID- 14698489
TI  - Effect of donor age on cultivation of human oral mucosal keratinocytes.
AB  - Cultured mucosal grafts (CMG) are among recently developed biological grafting
      materials to cover large oral mucosal defects following resection of mucosal
      pathology. This study evaluates the effect of donor's age on the cultivation
      process of oral mucosal keratinocytes for grafting. Human mucosal epithelial
      cells were utilized and classified into three donor age groups: 3-30 years (14
      patients); 31-60 years (9 patients); and >60 years (6 patients) (11 males and 18
      females). Isolation and cultivation of oral mucosal keratinocytes were according
      to Rheinwald and Green [Cell 6 (1975) 331], originally developed for epidermal
      keratinocytes. Isolated primary cell lines were seeded and cultivated.
      Propagation of cell lines ("passages"), time period required to reach confluence,
      yield of cells and plating efficiency were recorded. All cells propagated well up
      to the fourth passage. Thereafter, a decline was observed and was more distinct
      with age. Period to confluence was longer among the old age group. Yield of cells
      in fourth passage was high among the young age group and decreased with age.
      Plating efficiency in passages 4-6 decreased with age. These results suggest that
      age-related changes in cultivation of oral keratinocytes are not general
      phenomena, but rather limited to the donor age of 60 years and above. In this age
      group all the parameters studied were adversely affected. Oral mucosal
      keratinocytes may be a useful model for oral aging.

PMID- 14698490
TI  - Measuring the suffering of end-stage dementia: reliability and validity of the
      Mini-Suffering State Examination.
AB  - Assessment of suffering is extremely important in dying end-stage dementia
      patients (ESDP). We have developed and examined the reliability and validity of
      the Mini-Suffering State Examination (MSSE), in 103 consecutive bedridden ESDP.
      Main outcome measures included inter-observer reliability and concurrent
      validity. Reliability of the MSSE questionnaire was satisfactory, with Cronbach
      alpha values of 0.735 and 0.718 for the two physicians (Ph-1, Ph-2),
      respectively. The kappa agreement coefficient was 0.791. There was a high
      agreement for seven items (kappa 0.882-0.972) and a substantial agreement for the
      other three items (kappa 0.621-0.682) of the MSSE. MSSE was validated versus the
      comfort assessment in dying with dementia (CAD-EOLD) scale and resulted in a
      significant Pearson correlation (r=-0.796, P<0.001). We conclude that the MSSE
      scale is a reliable and valid clinical tool, recommended for evaluating the
      severity of the patient's condition and the level of suffering of ESDP. Use of
      MSSE may improve medical management and facilitate communication between patients
      and caregivers.

PMID- 14698491
TI  - Histopathological investigation of salivary glands in the asymptomatic elderly.
AB  - The significance of labial gland biopsies (LGBs) in the diagnosis of Sjogren's
      syndrome (SS) in the elderly has been a controversial subject since it is
      complicated by age-related histopathological changes. In an attempt to clarify
      the appropriateness of LGBs in present diagnosis criteria, we evaluated the
      specificity of LGBs using autopsied tissues. This was done by taking labial,
      sublingual and submandibular salivary glands from 53 autopsy subjects (24 males
      and 29 females) with an average age of 84 years, and testing them
      histopathologically with reference to a previously reported grading system. None
      had any sicca symptoms (oral dryness or dry eye). In subjects up to 75 years old,
      acinar atrophy was more frequent in labial glands than in the two major salivary
      glands (P=0.0098 for sublingual and P=0.0009 for submandibular glands). Also,
      while there were significant differences in frequency of such atrophy between the
      sublingual and submandibular salivary glands of subjects younger and older than
      75, the labial glands showed no such variation. Taking grade 3 (focus score of 1)
      as the diagnosis criterion, two subjects were determined to have SS in which case
      the specificity was 95%. Using contemporaneous serological test results for anti
      SSA/Ro antibodies as a diagnostic criterion raised specificity to 98%. For both
      major and minor glands, these appeared to be no relationship between degree of
      lymphocytic infiltration and age. Our results thus suggest that it is appropriate
      to adopt a focus score of 1 as a diagnostic criterion for SS in the elderly, and
      that serological test results can improve specificity.

PMID- 14698492
TI  - A polar diagram for comprehensive geriatric assessment.
AB  - Comprehensive geriatric assessment has become synonymous with geriatric practice.
      This includes evaluation of the older person's physical and mental health, and
      the functional and social status. We propose a new way of representing a person's
      condition, called the "polar diagram". This shows the subject's scores on the
      evaluation scales that are arranged in radial positions inside a circle. The
      outer part of the circle corresponds to the best condition. Gaps between the best
      condition and the actual scores are easily identified. The diagram can be
      employed to monitor the subject's condition and to assess any changes in
      outcomes.

PMID- 14698493
TI  - Is a Type A behavior pattern associated with falling among the community-dwelling
      elderly?
AB  - The aim of this report is to investigate the relationship between Type A behavior
      patterns and the likelihood of falling among community-dwelling elderly, and to
      compare differences in the prevalence, reasons, locations, injuries and frequency
      of falls between Type A and non-Type A personalities. Persons aged 60 or older
      living in 3 communities of Nanjing, China participated in a baseline survey
      conducted in 2000 (n=879), and falling incidents were followed for 1 year. The
      survey employed a self-administered questionnaire designed to elicit demographic
      data, current health problems and medications taken, intake of alcohol, exercise
      habits, physical function, environmental hazards and Type A behavior patterns.
      Several factors associated with falling such as health condition, physical
      function and environmental factors did not differ between the Type A and non-Type
      A groups except in the male tendency toward heart disease and their inability to
      walk fast. The results of logistic regression analyses showed that a Type A
      behavior pattern was independently associated with falling in males but not in
      females. Findings in the present study suggest that a Type A behavior pattern
      might play an important role in the rate of falling incidents in elderly males,
      since some characteristics of this personality pattern might lead to risk-taking
      behavior. More studies are needed to evaluate the association of certain behavior
      patterns with falling incidents.

PMID- 14698494
TI  - Functional status and active life expectancy among senior citizens in a small
      town in Japan.
AB  - The objectives of this study were to understand transition patterns and
      mechanisms of functional status, and to estimate active life expectancy (ALE)
      among senior citizens in a small town in Japan. With data drawn from surveys
      conducted annually from 1998 to 2002 (n=638 at baseline), prevalence and
      incidence of functional disability in activities of daily living (ADL) and
      instrumental activities of daily living (IADL) were described and compared
      between the sexes. Then relationships between potential predictors and functional
      decline through a 4-year follow-up were examined using logistic regression.
      Finally, active and disabled life expectancy was estimated by Katz's method. At
      baseline, 9 and 12% of subjects were dependent in performing ADL and IADL,
      respectively. Prevalence and incidence rates increased with age. The risk of
      mortality increased by 2.2-5.0-fold when the subject was functionally dependent
      at the previous year. Advanced age, difficulty in walking and poor interest were
      shown to be significant predictors of loss of independence in ADL. Mean durations
      with disability in ADL and IADL among women were longer than among men by around
      1 year. Population-specific preventive care programs considering physical,
      cognitive and social aspects are needed not only to maximize ALE but also to
      improve quality of life during survival period with disability especially in old
      women.

PMID- 14698495
TI  - Hypodermoclysis (subcutaneous infusion) effective mode of treatment of
      dehydration in long-term care patients.
AB  - Dehydration is associated with morbidity and mortality in frail elderly patients.
      Intravenous fluid administration in these patients is sometimes hard, especially
      in agitated patients. The purpose of this study was to review of 57 long-termed
      care patients received hypodermoclysis infusion on 118 different occasions during
      the 9 months. Data collection included: demographic data, functional and mental
      status, indication hypodermoclysis, duration of the infusion, type of solution,
      laboratory data, adverse effects, and outcome. The main reasons for initiation of
      the hypodermoclysis were either dehydration (64%) or febrile illness (21%). The
      average duration of infusions was 15.9 days and average daily volume was 1161 ml
      per day. After hydration by hypodermoclysis, in 77% of the patients, clinical
      improvement occurred manifested as general improvement (88%), cognitive status
      improvement (84%), and improved oral intake (81%). During the course of the
      study, failure of the treatment was observed in 12% of the patients, mortality of
      11% was observed. Nobody developed signs of fluid overload. Local complications
      were reported in 12% of patients: local swelling (6/57), complain of local pain
      at site (3/57) and local inflammation (2/57). Hypodermoclysis is a safe,
      effective and suitable alternative to intravenous re-hydration in long-term care
      patients.

PMID- 14698496
TI  - Frail elderly, nutritional status and drugs.
AB  - This review focuses on the interactions between nutritional status and drugs in
      frail elderly persons. Impairment of nutritional status, a component of clinical
      presentation in the frail elderly, has a major impact on the pharmacology of many
      drugs devolving from the physiological alterations it generates. Food itself
      plays a central role in nutritional status and in possible interactions with
      drugs. Conversely, drugs have often, directly and indirectly, a deleterious
      effect on the nutritional state of the elderly. However, research in this domain
      is scarce, and future clinical studies will need to include more elderly and
      frail elderly individuals, to help clinicians to better understand these
      interactions.

PMID- 14698497
TI  - Oxidative stress-associated vascular aging is independent of the protein kinase
      C/NAD(P)H oxidase pathway.
AB  - Aging is an independent risk factor for the development of cardiovascular
      disease. Vascular aging is mainly characterized by endothelial dysfunction,
      which, in turn, is primarily attributable to increased superoxide (O(2)(*)(-))
      formation with age. To date, the source of this age-associated increased O(2)(*)(
      ) production remains obscure. We investigated whether like in hyperglycemia or
      hypertension protein kinase C (PKC)-mediated activation of the NAD(P)H oxidase
      system is involved. Here we show that both PKC translocation, necessary for its
      activation, and expression of the cytosolic subunits of the NAD(P)H oxidase,
      p47(phox) and p67(phox), remain unchanged with age. Therefore, we suggest that
      oxidative stress-associated vascular aging mechanistically differs from
      endothelial dysfunction seen in the context of other cardiovascular risk factors,
      for which the PKC/NAD(P)H oxidase pathway has been shown responsible.

PMID- 14698498
TI  - Do systolic murmurs predict mortality in the elderly? A 15-year longitudinal
      population study of 70-year-olds.
AB  - Systolic murmurs are common in the elderly but there is a striking paucity
      regarding published reports on their clinical significance and relation with
      mortality. This study describes prevalence of systolic murmurs in the elderly and
      cardiovascular diseases in 70-year-olds with or without systolic murmurs, and
      investigates the relation between systolic murmurs at age 70 and 15-year
      mortality. This cohort study is based on 973 (449 males and 524 females) 70-year
      olds from Goteborg, Sweden who were examined in 1971/1972 at the Department of
      Geriatric Medicine, Goteborg University, and was followed-up to the year 2001.
      The prevalence of systolic murmur was 31% (females 36.4%, males 23.9%). Among
      subjects with systolic murmurs the prevalence of coronary heart disease (CHD) and
      hypertension was significantly higher in both sexes and congestive heart failure
      (CHF) in females only. Systolic murmur was a predictor for mortality in females
      (RR 1.49, 95% CI 1.17-1.91) but not in males (RR 1.14, 95% CI 0.89-1.49).
      Diagnosis of a cardiovascular disease was a significant predictor in both sexes
      for mortality irrespective of having systolic murmurs. In conclusion, there is a
      significant positive association of cardiovascular diseases with systolic murmurs
      in the elderly. The increased risk for mortality due to the presence of systolic
      murmur at age 70 is mediated through cardiovascular diseases.

PMID- 14698501
TI  - Anti-inflammatory activity of Jatropha curcas roots in mice and rats.
AB  - Anti-inflammatory activity of topical application of Jatropha curcas L. root
      powder in paste form in TPA-induced ear inflammation was confirmed in albino mice
      and the successive solvent extraction of these roots was carried out by ether and
      methanol. The methanol extract exhibited systemic and significant anti
      inflammatory activity in acute carrageenan-induced rat paw edema. It also showed
      activity against formalin-induced rat paw edema, as well as, turpentine-induced
      exudative changes and cotton pellet-induced granular tissue formation after oral
      treatment for 7 days in albino rats. Thus, resultant anti-inflammatory activity
      might be due to effects on several mediators and arachidonic acid metabolism
      involving cyclo-oxygenase pathway resulting in prostaglandin formation, anti
      proliferative activity leading to reduction in granular tissue formation and
      leukocyte migration from the vessels.

PMID- 14698500
TI  - Endothelium mediated vasorelaxant response of garlic in isolated rat aorta: role
      of nitric oxide.
AB  - The vasorelaxant effect of garlic (Alium sativum L.) has been suggested to be
      partially mediated through endothelium. The present study was designed to
      evaluate the role of various endothelium-mediated mechanisms in vasorelaxant
      response of garlic on isolated aortic rings of rats. In tissues precontracted
      with phenylephrine (PE) 10(-6)M, concentration-response curve for different
      concentrations of garlic (1, 5, 10, 20 and 50 microg/ml) was examined. In all the
      preparations garlic showed a concentration-dependent vasorelaxant response. There
      was a significant attenuation of vasorelaxation in tissues pretreated with K(+)
      channel blocker, glybenclamide (10(-6)M). Indomethacin (10(-5)M) enhanced the
      relaxant response of garlic. N(G)-Monomethyl-L-arginine (L-NMMA) 30 microM, a
      potent inhibitor of nitric oxide synthase, did not produce any significant effect
      on the response of garlic. However, cGMP blocker methylene blue (10(-5)M) showed
      a strong vasoconstriction and inhibited the vasorelaxant response of garlic. The
      results indicate that endothelium modulated vasorelaxation of garlic is partly
      mediated through EDHFs and cycloxygenase pathways. However, relaxing factor(s)
      other than NO, mediated through cGMP has a major role in the vasorelaxant
      response of garlic.

PMID- 14698502
TI  - Anti-angiogenic and inhibitory activity on inducible nitric oxide production of
      the mushroom Ganoderma lucidum.
AB  - Fresh fruit bodies of Ganoderma lucidum were extracted with 70% ethanol at room
      temperature. The extract (GL) showed significant anti-angiogenic activity, which
      was detected using a chick embryo chorioallantoic membrane assay. GL
      significantly inhibited LPS-induced NO production in RAW 264.7 macrophages. These
      results support the anti-tumor effect of Ganoderma lucidum.

PMID- 14698503
TI  - Anti-steroidogenic activity of the two Indian medicinal plants in mice.
AB  - The chloroform extract of Croton roxburghii bark (CECR, Euphorbiaceae) and ethyl
      acetate extract of Zizyphus jujuba bark (EAZJ, Rhamnaceae) were evaluated for
      anti-steroidogenic activity in the adult female mouse. This study was designed to
      assess the effects of CECR and EAZJ on ovarian steroidogenisis. Antifertility
      activity was evaluated by observing the estrus cycle, body weight, wet weight of
      ovaries, steroidogenic enzymes, and substrates. Blood profiles were estimated to
      find out the toxic manifestations of the extracts. CECR and EAZJ each arrested
      the normal estrus cycle of adult female mouse at diestrus stage and reduced the
      wet weight of ovaries significantly. Cholesterol and ascorbic acid content in
      ovaries of crude extract-treated mice were significantly elevated. The
      significant inhibition of delta(5)-3beta-hydroxysteroid dehydrogenase (delta(5)
      3beta-HSD) and glucose-6-phosphate dehydrogenase (G-6-PDH), the two key enzymes
      involved in ovarian steroidogenisis, were also observed in mouse after 18 days of
      treatment. Hematological profiles, biochemical estimations of whole blood and
      serum remains unaltered in extract-treated mouse. Normal estrus cycle and ovarian
      steroidogenisis were restored after withdrawal of treatment with CECR and EAZJ on
      average 27 and 32 days, respectively. Antifertility activities of crude extracts
      were found to be reversible.

PMID- 14698504
TI  - Pharmacological screening of six Amaryllidaceae species.
AB  - Dichloromethane and 90% methanol extracts of different parts of 6 Amaryllidaceae
      species were investigated for anti-inflammatory (COX-1 and COX-2), antibacterial
      and mutagenic (Salmonella/microsome test strain TA98) activities. Antibacterial
      activity was carried out using disc diffusion assay against three Gram-positive
      (Bacillus subtilis, Staphylococcus aureus and Microccus luteus) and two Gram
      negative (Escherichia coli, Klebsiella pneumoniae) bacteria. With the exception
      of the leaf of Cyrtanthus mackenii, all CH(2)Cl(2) extracts of different parts of
      Cyrtanthus species inhibited the growth of at least one bacterium, with the
      CH(2)Cl(2) bulb/root extracts of Cyrtanthus suaveolens showing broad-spectrum
      antibacterial activity. In the anti-inflammatory assay, CH(2)Cl(2) extracts,
      resuspended at 500 microg/ml, from different parts of all species under
      investigation, inhibited activity of both COX-1 and COX-2 by at least 70%. The
      most active, 90% methanolic extracts (resuspended at 500 microg/ml) were from the
      leaves (78%) and roots (76%) of Cyrtanthus falcatus and the leaves of Gethyllis
      ciliaris (70%). Only CH(2)Cl(2) extracts of Cyrtanthus falcatus (leaf and root)
      and Cyrtanthus suaveolens (bulb/root and leaf) had a mutagenic effect in the
      Salmonella/microsome assay strain TA98.

PMID- 14698505
TI  - In vitro cytotoxic activity of Thai medicinal plants used traditionally to treat
      cancer.
AB  - The SRB assay was used to test cytotoxicity against three human cancer cell lines
      and one normal cell line of 11 Thai medicinal plant species used by traditional
      doctors in treating cancer patients. The extraction procedures used were similar
      to those practised by Thai traditional doctors (ethanolic and water extracts).
      Extracts were tested against the human large cell lung carcinoma cell line COR
      L23, the human breast adenocarcinoma cell line MCF-7 and human colon
      adenocarcinoma cell line LS-174T and normal human keratinocytes SVK-14. The
      results showed that three plants; Dioscorea membranacea Pierre ex Prain &
      Burkill, Dioscorea birmanica Prain & Burkill (Dioscoreaceae) and Siphonodon
      celastrineus Griff. (Celastraceae), exhibited high cytotoxic activity showing a
      certain degree of selectivity against the different cell types.

PMID- 14698506
TI  - Hypoglycemic effect of Rehmannia glutinosa oligosaccharide in hyperglycemic and
      alloxan-induced diabetic rats and its mechanism.
AB  - The hypoglycemic and anti-diabetic effect of Rehmannia glutinosa oligosaccharide
      (ROS) in glucose-induced hyperglycemic and alloxan-induced diabetic rats and its
      mechanism was investigated in this paper. It was found that pretreatment of ROS
      in normal rats with 100 mg/kg for 3 days, i.p., induced a partial prevention of
      hyperglycemia caused by glucose (2g/kg, i.p.), while when hyperglycemia was
      induced in adrenalectomized (ADX) rats, the preventive effect of ROS on
      hyperglycemia was lost. In alloxan-induced diabetic rats, ROS (100 mg/kg for 15
      days, i.p.) showed a significant decrease in blood glucose level and hepatic
      glucose-6-phosphatase activity with an increase in hepatic glycogen content.
      Furthermore, ROS raised plasma insulin level and lowered plasma corticosterone
      level in alloxan-induced diabetic rats. The results indicated that
      oligosaccharide of Rehmannia glutinosa Libosch. exerted a significant
      hypoglycemic effect in normal and alloxan-induced diabetic rats. The regulatory
      mechanism of ROS on glucose metabolism was adrenal dependent and had a close
      relation with the neuroendocrine system.

PMID- 14698507
TI  - The analgesic effect of the methanolic extract of Acanthus montanus.
AB  - The analgesic effect of the methanolic leaf extract of Acanthus montanus was
      studied in rats using the cold water tail flick assay, and in mice using the tail
      immersion, tail clip, acetic acid induced writhing and formalin pain tests. The
      results showed dose-dependent and significant (P<0.05) increases in pain
      threshold, at 60 min post treatment, with doses of 200 and 400 mg/kg of the
      extract in tail flick, tail immersion and tail clip methods. The effects of the
      extract were significantly (P<0.05) lower than those produced by morphine (10
      mg/kg) in the same tests. The extract (100-400 mg/kg) exhibited a dose-dependent
      inhibition of writhing and also showed a significant (P<0.001) inhibition of both
      phases of the formalin pain test, but with a less intense effect on the first
      than on the second phase. The results indicate that the analgesic effect of
      Acanthus montanus methanolic extract is both centrally and peripherally mediated.

PMID- 14698508
TI  - Immunoprotection by botanical drugs in cancer chemotherapy.
AB  - Most of the synthetic chemotherapeutic agents available today are
      immunosuppressants, cytotoxic, and exert variety of side effects that are
      particularly evident in cancer chemotherapy. Botanical based immunomodulators are
      often employed as supportive or adjuvant therapy to overcome the undesired
      effects of cytotoxic chemotherapeutic agents and to restore normal health. Total
      extract, polar and non-polar extracts, and their formulations, prepared from
      medicinal plants mentioned in Ayurveda, namely, Withania somnifera (Linn Dunal)
      (Solanaceae), Tinospora cordifolia (Miers) (Menispermaceae), and Asparagus
      racemosus (Willd.) (Liliaceae), exhibited various immunopharmacological
      activities in cyclophosphamide (CP)-treated mouse ascitic sarcoma. Treatment of
      ascitic sarcoma-bearing mice with a formulation of total extracts of Withania
      somnifera and Tinospora cordifolia (80:20) and alkaloid-free polar fraction of
      Withania somnifera resulted in protection towards CP-induced myelo- and
      immunoprotection as evident by significant increase in white cell counts and
      hemagglutinating and hemolytic antibody titers. Treatment with these candidate
      drugs will be important in development of supportive treatment with cancer
      chemotherapy.

PMID- 14698509
TI  - Cordyceps sinensis extracts do not prevent Fas-receptor and hydrogen peroxide
      induced T-cell apoptosis.
AB  - Aqueous and alcohol extracts of Cordyceps sinensis (Berk) Succ. are used as a
      traditional medicine in China for the treatment of a wide range of diseases and
      are reported to have antioxidant and antiapoptotic properties. We therefore
      examined the ability of aqueous, organic, and alcohol extracts of Cordyceps
      sinensis to inhibit apoptosis induced either by hydrogen peroxide or Fas-receptor
      ligation; both stimuli induce apoptosis dependent on reactive oxygen species.
      Cells pre-incubated with Cordyceps sinensis extracts were equally sensitive to
      hydrogen peroxide and Fas-mediated apoptosis. Thus, the putative antioxidant and
      antiapoptotic properties of Cordyceps sinensis are insufficient to rescue cells
      from apoptosis induced by these stimuli in vitro.

PMID- 14698510
TI  - Hypolipidemic effect of different extracts of Clerodendron colebrookianum Walp in
      normal and high-fat diet fed rats.
AB  - Clerodendron colebrookianum Walp (family, Verbenaceae) has been used as a home
      remedy by the Mizo people of north eastern (NE) region of India in their folklore
      medicine as a cardioprotective (mainly against high blood pressure) agent. The
      scientific basis for their use has yet to be established. Therefore, in this
      investigation an attempt has been made to study the effect of different extracts
      of the leaves of Clerodendron colebrookianum Walp (CC) on serum lipid profile
      which is closely associated with many cardiovascular diseases. It was found that
      after administration of both crude and organic extracts the serum lipid profile,
      i.e. total cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL)
      lowered significantly (P<0.001) from their respective control except TG in
      methanol extract (ME)-treated rats. The decreased percentage of TC, TG and LDL
      after administration of crude extract (CE) and ethylacetate extract (EE) with
      normal diet were found to be 35, 39 and 48%, and 33, 18 and 91%, respectively,
      after 7 days of treatment. In case of ME the lowering of TC and LDL were noted to
      be 41 and 85%, respectively. Both TC and TG were lowered significantly (P<0.001)
      even after the administration of crude extract against high-fat diet. Significant
      increase of cardioprotective lipid, i.e high density lipoprotein (HDL) after
      administration of EE (46%) and ME (38%) was another interesting finding of this
      experiment. Total cholesterol:HDL and LDL:HDL ratios were significantly lower in
      the experimental group. Therefore, it was concluded that the leaves of CC have
      definite cardioprotective potentiality, and there is a valid scientific basis for
      consuming it for better health in NE region of India.

PMID- 14698511
TI  - Anti-inflammatory and analgesic activities of Mallotus spodocarpus Airy shaw.
AB  - The chloroform extract from the roots of Mallotus spodocarpus was investigated
      for anti-inflammatory and analgesic activities in animal models. In acute
      inflammatory models, the extract significantly inhibited ethyl phenylpropiolate
      induced ear edema and carrageenin- and arachidonic acid-induced hind paw edema in
      rats. In the chronic inflammatory model using the cotton pellet-induced granuloma
      in rats, the extract exhibited inhibitory activity on the formation of granuloma.
      The extract also elicited pronounced inhibitory effect on acetic acid-induced
      writhing response in mice in the analgesic test. The results obtained suggest
      marked anti-inflammatory and analgesic activity of the extract.

PMID- 14698512
TI  - Antimutagenic activity of flavonoids from the heartwood of Rhus verniciflua.
AB  - Pretreatment of the methanolic extract of the heartwood of Rhus verniciflua
      (Anacardiaceae) to rats prevented the activation of hepatic microsomal cytochrome
      p(450) enzymes, inhibition of hepatic glutathione S-transferase by bromobenzene
      treatment, respectively, and therefore significantly decreased malondialdehyde
      content in the rat. The Ames test showed that the addition of 1.0 mg/plate of the
      methanolic extract or the EtOAc fraction of the Rhus verniciflua heartwood
      extract potentially inhibited the mutagenicity by aflatoxin B(1). Column
      chromatography of the EtOAc fraction yielded four flavonoids, garbanzol (1),
      sulfuretin (2), fisetin (3), fustin (4), mollisacasidin (5). When these
      components were subjected to the Ames test, it was found that sulfuretin might
      effectively prevent the metabolic activation or scavenge electrophilic
      intermediates capable of causing mutation. In contrast, fustin showed a dose
      independent antimutagenic activity and it has mutagenic/antimutagenic activity.
      However, a mixture of sulfuretin and fustin (1:1) exhibited dose-dependent
      antimutagenicity indicating that sulfuretin inhibited the mutagenicity of fustin.
      These results suggest that the extract of Rhus verniciflua heartwood containing
      flavonoid complex could be a potent anticarcinogen.

PMID- 14698513
TI  - Effect of Aerva lanata on cisplatin and gentamicin models of acute renal failure.
AB  - The ethanol extract of the entire plant of Aerva lanata was studied for its
      nephroprotective activity in cisplatin- and gentamicin-induced acute renal injury
      in albino rats of either sex. In the curative regimen, the extract at dose levels
      of 75, 150 and 300 mg/kg showed dose-dependent reduction in the elevated blood
      urea and serum creatinine and normalized the histopathological changes in the
      curative regimen. In the gentamicin model the rats in the preventive regimen also
      showed good response to the ethanol extract at 300 mg/kg. The findings suggest
      that the ethanol extract of Aerva lanata possesses marked nephroprotective
      activity with minimal toxicity and could offer a promising role in the treatment
      of acute renal injury caused by nephrotoxins like cisplatin and gentamicin.

PMID- 14698514
TI  - Mosquitocidal activities of octacosane from Moschosma polystachyum Linn
      (lamiaceae).
AB  - The toxicity of the plant Moschosma polystachyum was evaluated against mosquito
      Culex quinquefasciatus. The crude leaf extract and active compound octacosane
      showed negligible mortality against early third instar larvae of Culex
      quinquefasciatus. The 24 h LC(50) value was observed at 153.2+/-1.3 mg/l and
      7.2+/-1.7 mg/l for crude leaf extract and active compound octacosane,
      respectively. The repellent activity of active compound octacosane at 1.0 and 2.5
      mg/cm(2) concentration gave 85.2+/-1.7 min and 54.6+/-2.3 min protection,
      respectively. The total percentage protection of octacosane was 96.2+/-0.9 at 2.5
      mg/cm(2) and 86.4+/-1.3 at 1.0 mg/cm(2) concentration.

PMID- 14698515
TI  - Antiparasitic activities of medicinal plants used in Ivory Coast.
AB  - During an ethnopharmacological survey of antiparasitic medicinal plants used in
      Ivory Coast, 17 plants were identified and collected. Polar, non-polar and
      alkaloidic extracts of various parts of these species were evaluated in vitro in
      an antiparasitic drug screening. Antimalarial, leishmanicidal, trypanocidal,
      antihelminthiasis and antiscabies activities were determined. Among the selected
      plants, Anogeissus leiocarpus and Terminalia glaucescens were strongly active
      against Plasmodium falciparum. Lawsonia inermis, selectively prescribed against
      trypanosomiasis shows interesting trypanocidal activities as did other 15 plants.
      Anthelmintic activities were found for 10 active species and 2 species (Uvaria
      afzelli and Monodora myristica) were actives against mites.

PMID- 14698516
TI  - Evaluation of antiplaque activity of Azadirachta indica leaf extract gel--a 6
      week clinical study.
AB  - Various chemical agents have been evaluated over the years with respect to their
      antimicrobial effects in the oral cavity; however, all are associated with side
      effects that prohibit regular long-term use. Therefore, the effectiveness of neem
      (Azadirachta indica A. Juss) leaf extract against plaque formation was assessed
      in males between the age group of 20-30 years over a period of 6 weeks. Present
      study includes formulation of mucoadhesive dental gel containing Azadirachta
      indica leaf extract (25 mg/g). A 6-week clinical study was conducted to evaluate
      the efficacy of neem extract dental gel with commercially available chlorhexidine
      gluconate (0.2% w/v) mouthwash as positive control. Microbial evaluation of
      Streptococcus mutans and Lactobacilli species was carried out to determine the
      total decrease in the salivary bacterial count over a period of treatment using a
      semi-quantitative four quadrant streaking method. The results of the study
      suggested that the dental gel containing neem extract has significantly (P<0.05)
      reduced the plaque index and bacterial count than that of the control group.

PMID- 14698517
TI  - Amrita Bindu--an antioxidant inducer therapy in asthma children.
AB  - Studies all over the world on the therapeutic use of antioxidants as supplements
      has revealed their capacity to control inflammatory processes. Amrita Bindu an
      Ayurvedic health food supplement has already shown to be an antioxidant inducer
      and to combat free radical-mediated tissue damage studied in rats. Amrita Bindu
      is a salt-spice herbal mixture designed for positive health. It was tested as a
      supplement to therapy for a period of 12 months in 36 children suffering from
      asthma. Asthma is a chronic inflammatory disease with excessive free radical
      generation in lungs and blood cells. The patients were followed up by monitoring
      their clinical conditions, therapeutic doses of anti-asthmatic drugs, free
      radical generation, lipid peroxidation (LPO) and antioxidants in blood. At the
      end of 3 months of Amrita Bindu supplementation, the patients had stopped all
      anti-asthmatic medications and were free from attacks of asthma.

PMID- 14698518
TI  - Anti-nociceptive and anti-inflammatory activities of the methanolic extract of
      Parinari polyandra stem bark in rats and mice.
AB  - The methanolic extract of the stem bark of Parinari polyandra (family Rosaceae)
      was investigated for possible anti-nociceptive and anti-inflammatory effects in
      mice and rats. Three models were used to study the extracts effects on
      nociception which were the acetic acid-induced abdominal constriction test, hot
      plate method (both in mice) and the formalin test in rats. The anti-inflammatory
      effects were investigated employing the albumin-induced hind-paw oedema in rats.
      Results of the study revealed the extract to have significant (P<0.05) anti
      nociceptive effect at a dose of 200 mg/kg p.o. in mice and rats in all the models
      for anti-nociception while 100 mg/kg p.o. showed significant (P<0.05) effect in
      the acetic acid-induced abdominal constriction test and in phase I of the
      formalin test. The extract also exhibited anti-inflammatory effects which were
      found to be significant (P<0.05) at 200 mg/kg p.o. in the rats tested.
      Preliminary phytochemical screening of the extract showed the presence of
      flavonoids, tannins, and saponin glycoside. The results suggest the extract
      contains pharmacologically active principles. The result is in agreement with the
      local application of the plant in painful and inflammatory conditions.

PMID- 14698519
TI  - Anti-ulcer and antioxidant activity of DHC-1, a herbal formulation.
AB  - DHC-1, a herbal formulation, was tested for its anti-ulcer and antioxidant
      activity in rats. Effect of various doses (125, 250, 500, and 1000 mg/kg, p.o.)
      of DHC-1 was studied on gastric secretion and gastric ulcers in pylorus-ligation
      and on ethanol-induced gastric mucosal injury in rats. The reduction in ulcer
      index in both the models along with the reduction in volume and total acidity,
      and an increase in the pH of gastric fluid in pylorus-ligated rats proved the
      anti-ulcer activity of DHC-1. The increase in the levels of superoxide dismutase
      (SOD), catalase (CAT), reduced glutathione (GSH) and membrane bound enzymes like
      Ca(2+)ATPase, Mg(2+)ATPase, and Na(+)K(+)ATPase and decrease in lipid
      peroxidation (MDA) in both the models showed the antioxidant activity of the
      formulation. Thus, it can be concluded that DHC-1 possesses anti-ulcer activity,
      which can be attributed to its antioxidant mechanism of action.

PMID- 14698520
TI  - Brine shrimp toxicity and antiplasmodial activity of five Kenyan medicinal
      plants.
AB  - The organic extracts of leaves and roots of five plants used for treating malaria
      in Central, Nairobi and Rift Valley Provinces, Kenya were tested for brine shrimp
      lethality and in vitro antiplasmodial activity against chloroquine sensitive and
      resistant strains of Plasmodium falciparum. Of the plants tested, 60% were toxic
      to the brine shrimp (LC(50)<30 microg/ml) and eight out of ten plant parts (80%)
      showed in vitro antiplasmodial activity (IC(50)<50 microg/ml). Among the extracts
      screened, the leaves of Cyathula polcephala had the highest toxicity to the brine
      shrimp (LC(50)=2.9 microg/ml) while the leaves of Pentas longiflora had the best
      antiplasmodial activity (IC(50)=11. /ml). The plant extracts with low IC(50)
      values are potential sources for novel antiplasmodial compounds.

PMID- 14698521
TI  - Ethnopharmacological studies of antimicrobial remedies in the south of Brazil.
AB  - This study reports the antimicrobial evaluation of the species most commonly used
      in Rio Grande do Sul (RS), the southernmost state of Brazil, for treating
      conditions likely to be associated with microorganisms. A four-stage process of
      documentation and evaluation was conducted: (a). review of RS ethnobotanical
      studies; (b). analysis of traditional uses; (c). literature survey on
      phytochemical and pharmacological data; (d). microbiological screening of
      selected plants. From the 149 species initially identified, 49 were cited as
      being used for microbial associated conditions in at least two other regions in
      RS, and 18 were further selected for screening. The crude methanol extract of
      these 18 plants were evaluated against seven microorganisms using the diffusion
      agar test. Extracts from Chaptalia nutans, Cordia monosperma, Echinodorus
      grandiflorus, Eugenia uniflora, Leonurus sibiricus, Luehea divaricata, Malva
      sylvestris, Ocotea odorifera, Parapiptadenia rigida, Pluchea sagittalis, Psidium
      cattleyanum and Senna neglecta were active against at least one microorganism.
      Although preliminary, these results are useful for rationalizing the use of
      medicinal plants in established systems of traditional medicine in primary health
      care.

PMID- 14698522
TI  - The effects of Cassia auriculata and Cardiospermum halicacabum teas on the steady
      state blood level and toxicity of carbamazepine.
AB  - A study was conducted using male Wistar rats as the experimental model, to
      compare the effects of concurrent administration of herbal tea prepared from
      dried flowers of Cassia auriculata or aerial parts of Cardiospermum halicacabum
      and carbamazepine, on (a). steady state serum levels of the prescription drug,
      and (b). changes in toxicity (as assessed by changes in general behaviour,
      haematological parameters, and liver and kidney function) that may occur due to
      drug interaction. Results demonstrate that in rats receiving the Cassia
      auriculata tea and carbamazepine, the blood levels of the prescription drug were
      significantly enhanced by 47.1% (P<0.04), when compared with the levels in
      animals receiving only carbamazepine for the same time period, with no apparent
      changes in toxicity. In animals receiving the Cardiospermum halicacabum tea,
      there were no significant changes in the blood levels of carbamazepine or drug
      related toxicity. Cassia auriculata tea has therefore the potential to influence
      the bioavailability of carbamazepine, and hence its therapeutic actions.
      Concurrent ingestion of carbamazepine with herbal teas containing Cassia
      auriculata is therefore best avoided by patients under treatment for epilepsy.

PMID- 14698523
TI  - Hepatoprotective effect of allicin on tissue defense system in
      galactosamine/endotoxin challenged rats.
AB  - Allicin (diallythiosulfinate) is the main biologically active component of
      freshly crushed garlic (Alliaceae Allium sativum Linn.) cloves. It is produced by
      the interaction of the non-protein amino acid alliin with the enzyme alliinase
      (alliin lyase, EC 4.4.1.4). D-Galactosamine highly sensitizes the host response
      of the experimental animal to endotoxin (lipopolysaccharide) and causes fulminant
      hepatitis within 8h after administration. In D-galactosamine/lipopolysaccharide
      (D-GalN/LPS)-induced hepatitis rats, a significant increase of lipid peroxidation
      and decreased liver antioxidant enzyme levels are observed. Pretreatment with
      allicin, the active component of freshly crushed garlic cloves, prevented these
      alterations.

PMID- 14698524
TI  - Ethanolic extract of Ocimum sanctum leaves partially attenuates streptozotocin
      induced alterations in glycogen content and carbohydrate metabolism in rats.
AB  - Ocimum sanctum (OS) has been mentioned in Indian system of traditional medicine
      to be of value in the treatment of diabetes mellitus. We have previously shown
      that OS shows a dose-dependent hypoglycemic effect and prevented rise in plasma
      glucose in normal rats. It also showed significant antihyperglycemic effect in
      STZ-induced diabetes. The present study was undertaken to assess the effect of OS
      on three important enzymes of carbohydrate metabolism [glucokinase (GK) (EC
      2.7.1.2), hexokinase (HK) (EC 2.7.1.1) and phosphofructokinase (PFK) (EC
      2.7.1.11)] along with glycogen content of insulin-dependent (skeletal muscle and
      liver) and insulin-independent tissues (kidneys and brain) in STZ (65 mg/kg)
      induced model of diabetes for 30 days. Administration of OS extract 200mg/kg for
      30 days led to decrease in plasma glucose levels by approximately 9.06 and 26.4%
      on 15th and 30th day of the experiment. Liver and two-kidney weight expressed as
      percentage of body weight significantly increased in diabetics (P<0.0005) versus
      normal controls. OS significantly decreased renal (P<0.0005) but not liver
      weight. Renal glycogen content increased by over 10 folds while hepatic and
      skeletal muscle glycogen content decreased by 75 and 68% in diabetic controls
      versus controls. OS did not affect glycogen content in any tissue. Activity of
      HK, GK and PFK in diabetic controls was 35, 50 and 60% of the controls and OS
      partially corrected this alteration.

PMID- 14698525
TI  - Antiproliferation, antioxidation and induction of apoptosis by Garcinia
      mangostana (mangosteen) on SKBR3 human breast cancer cell line.
AB  - This study was designed to determine the antiproliferative, apoptotic and
      antioxidative properties of crude methanolic extract (CME) from the pericarp of
      Garcinia mangostana (family Guttiferae) using human breast cancer (SKBR3) cell
      line as a model system. SKBR3 cells were cultured in the presence of CME at
      various concentrations (0-50 microg/ml) for 48 h and the percentage of cell
      viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-di phenyl tetrazolium
      bromide (MTT) assay. CME showed a dose-dependent inhibition of cell proliferation
      with ED(50) of 9.25+/-0.64 microg/ml. We found that antiproliferative effect of
      CME was associated with apoptosis on breast cancer cell line by determinations of
      morphological changes and oligonucleosomal DNA fragments. In addition, CME at
      various concentrations and incubation times were also found to inhibit ROS
      production. These investigations suggested that the methanolic extract from the
      pericarp of Garcinia mangostana had strong antiproliferation, potent
      antioxidation and induction of apoptosis. Thus, it indicates that this substance
      can show different activities and has potential for cancer chemoprevention which
      were dose dependent as well as exposure time dependent.

PMID- 14698526
TI  - Effects of Azadirachta indica extract on gastric ulceration and acid secretion in
      rats.
AB  - The effect of Azadirachta indica extract on gastric ulceration was studied in
      albino rats. Azadirachta indica extract (100-800 mg/kg p.o., 100-25 mg/kg i.p.)
      significantly inhibited gastric ulceration induced by indomethacin (40 mg/kg).
      Administration of 800 mg/kg p.o. and 250 mg/kg i.p. caused 100% cytoprotection
      against indomethacin (40mg/kg, i.p.)-induced gastric ulceration. This action was
      accompanied by a dose-dependent decrease in total gastric acidity. In order to
      investigate the probable mechanism of Azadirachta indica antiulcer activity, the
      effect of the extract alone and in combination with histamine (1mg/kg) and
      cimetidine (0.12 mg/kg) on gastric acid secretion in situ was studied.
      Azadirachta indica (250 mg/kg) significantly inhibited the basal and histamine
      induced gastric acid secretion. Cimetidine seemed to augment Azadirachta indica
      inhibition of gastric acid secretion. The results suggest that the stem bark
      extract of Azadirachta indica possesses antiulcer agents, which probably act via
      histamine H(2) receptor.

PMID- 14698527
TI  - Folk herbal medicines used in birth control and sexual diseases by tribals of
      southern Rajasthan, India.
AB  - An ethnobotanical survey of tribal area of southern Rajasthan was carried out
      during the year 2001-2002 for ethnosexicological herbal medicines. The
      information on ethnosexicological herbs is based on the exhaustive interview with
      local medicine-men and -women, birth attendants and other knowledgeable persons
      who prescribe their own herbal preparation to check birth control, including
      abortion at initial stages, preventing conception or by making either member of
      the couple sterile and to cure various sexual diseases like leucorrhoea,
      gonorrhoea, menorrhagia, to regularize menses and syphilis in both the sexes.
      During ethnobotanical survey, 53 plants belonging to 33 families have been
      reported from the study area, which are used to cure sexual diseases, and for
      family planning. A list of plant species along with their local name, habit,
      flowering and fruiting period, plant part/s used and the mode of administration
      to cure the sexual diseases are given.

PMID- 14698531
TI  - Women's susceptibility to tobacco carcinogens.
AB  - STUDY OBJECTIVES: To assess lung cancer risk of smoking women relative to that of
      equally smoking men. METHODS: The study base was constituted by baseline CT
      screenings for lung cancer on 1202 women and 1288 men, at least 40 years of age
      and with at least 10 pack-years of cigarette smoking. The prevalence-odds
      (incidence-density) ratio contrasting women with men was calculated. Confoundings
      by age and the particulars of smoking history were controlled in logistic
      regression analysis. RESULTS: For the prevalence-odds ratio contrasting women
      with men, upon control of age and smoking history, the point estimate was 2.7 and
      the 95% interval estimate 1.6-4.7. The diagnosed cancers were of equally
      'aggressive' types between the two genders. CONCLUSIONS: At variance with
      evidence from cohort studies, this evidence from a screening experience calls for
      further consideration of the hypothesis that women are more susceptible to
      tobacco carcinogens than are men.

PMID- 14698532
TI  - Population-based outcomes for small cell lung cancer: impact of standard
      management policies in British Columbia.
AB  - Survival data for small cell lung cancer (SCLC) is typically reported from
      clinical trials or institutional series that include patients fit enough to meet
      treatment criteria. The denominator of all SCLC patients from which the treated
      population is derived is rarely reported and the impact of new treatment
      strategies on population-based outcomes is difficult to measure. The British
      Columbia Cancer Agency (BCCA) is a single centralized agency that coordinates
      cancer treatment services in the province and develops and circulates province
      wide treatment guidelines. All SCLC cases diagnosed in BC in 1990 and 1995 (n=331
      and 297, respectively) were identified. These 2 years were chosen specifically to
      examine the impact of a change in practice guidelines from consolidative to early
      concurrent thoracic radiation (RT) for patients with limited stage disease.
      Demographic, staging, treatment, and outcome details were obtained for 100% of
      cases. A total of 628 patients were reviewed, 207 with limited stage disease
      (LSCLC) and 407 with extensive stage disease (ESCLC); 14 cases diagnosed at post
      mortem were excluded. Of the 207 patients with LSCLC disease, 170 (82%) received
      chemotherapy, and 138 (81%) of those that received chemotherapy also received
      thoracic radiation. A similar proportion (73 and 70%) of LSCLC patients received
      thoracic RT in both years but more patients in 1995 received early concurrent
      versus consolidative thoracic RT compared to those treated in 1990 (64% versus
      17%, respectively, P=0.001). Of the 407 patients with ESCLC, 71% received
      chemotherapy. The median overall survival for all patients was 7 months. Patients
      with LSCLC who received any chemotherapy had a median survival of 14.3 months
      (26.9 and 9.9% for 2- and 5-year survival, respectively). Patients with LSCLC who
      received chemotherapy plus thoracic RT had a median survival of 15.1 months (32
      and 12% for 2- and 5-year survival, respectively). Early concurrent thoracic RT
      in LSCLC was associated with an improved 5-year survival from 9.6 to 16.3%
      (P=0.91). Patients with ESCLC who received any chemotherapy had a median survival
      of 8.4 months (7.3 and 2.3% for 2- and 5-year survival, respectively). Standard
      treatment guidelines generated population-based survival outcomes that are
      similar to published clinical trials.

PMID- 14698533
TI  - Dexamethasone regulation of gastrin-releasing peptide receptor in human lung
      cells.
AB  - We investigated the effects of the glucocorticoid, dexamethasone (Dex), on
      expression of the gastrin-releasing peptide (GRP) receptor by human small cell
      lung carcinoma (SCLC) SHP77 cells. After 12h of 10nM Dex exposure, a six-fold
      increase in the peak of GRP receptor mRNA compared with untreated controls
      (10.5+/-4 versus 1.65+/-0.15 attomols/microg total RNA, respectively, P<0.05)
      occurred. GRP receptor mRNA levels fell to less than 0.5 attomols/microg total
      RNA after 24h; in Dex-treated cells, these levels rose to 1.2 compared with 0.12
      attomols/microg total RNA in the absence of Dex after 7 days. A significant
      increase (P<0.05) in the GRP receptor-specific binding was also found.
      Stimulation of SHP77 cell proliferation (25-35% in the presence of 10-100 nM Dex;
      P<0.0001) was observed after 4-8 days of exposure; this stimulation was inhibited
      by GRP receptor antagonists. SHP77 cell content and concentration of bombesin
      like peptides (BLP) in conditioned medium (approximately 4 nM) was unchanged by
      Dex. Stimulation of human SCLC SHP77 cell proliferation by Dex may, in part,
      occur via effects on the GRP autocrine system in these cells.

PMID- 14698534
TI  - Lung cancer detection by a RT-nested PCR using MAGE A1--6 common primers.
AB  - BACKGROUND: Since the mortality of lung cancer patients remains very high, the
      development of a sensitive detection method remains an urgent task. The authors
      have designed common melanoma antigen gene (MAGE) primers that enable the
      detection of MAGE A1 to A6 subtypes simultaneously. These primers were applied to
      the detection of lung cancer using sputum specimens. METHODS: The study involved,
      53 cancer patients and three non-cancer groups (193 healthy people, 235 lung
      cancer screening group and 140 patients with benign lung diseases) were
      investigated. One hundred and thirty-six respiratory specimens (55 random sputa,
      33 induced sputa, 40 broncho-alveolar lavage (BAL) fluids, and 8 pleural fluids)
      from different lung cancer patients were blindly tested. The MAGE assay was
      performed by RT-nested PCR, and the results obtained from sputum were compared
      with those obtained by telomerase assay and conventional cytology. RESULTS: In
      the sputum of the non-cancer groups, the positive rates were less than 2.1%,
      while the detection rates were 83.3% in the cancer tissues and 54.3% in the sputa
      of lung cancer patients. For the random sputum samples of lung cancer patients,
      the detection rate was 47.5%, but in the induced sputum, BAL and pleural fluids,
      the detection rate was up to over 70.0%. The MAGE assay produced a higher
      detection rate than the telomerase assay and conventional cytology. CONCLUSIONS:
      MAGE A1-6 RT-PCR, which showed high sensitivity and specificity, provides an
      effective means for the lung cancer detection in sputum.

PMID- 14698535
TI  - Clinical-radiological presentation and outcome of surgically treated pulmonary
      carcinoid tumours: a long-term single institution experience.
AB  - PURPOSE: To determine the presenting features and the outcome of surgically
      treated pulmonary carcinoid tumours. METHODS: Retrospective analysis of all
      consecutive cases with preoperatively suspected or proven pulmonary carcinoid,
      treated between 1964 and 1994, in order to have full 5-year survival data.
      RESULTS: Seventy-three patients were retrieved, six had a postoperative histology
      other than carcinoid. The mean age of the 67 eligible cases was 44 years (range
      17-74). There were 59 typical and eight atypical carcinoids. The most frequent
      presenting symptom was infection, followed by haemoptysis. Sixteen patients were
      asymptomatic, 15 of these had an abnormal chest X-ray, showing a solitary nodule
      in 13. Bronchoscopy was abnormal in almost all symptomatic patients. Bronchial
      biopsy results suggested a malignancy other than carcinoid in seven of eight
      patients whose postoperative histology was found to be atypical carcinoid. There
      were 40 lobectomies, 14 bi-lobectomies, nine pneumonectomies, and four limited
      resections. Ten patients had lymph node involvement (seven typical and three
      atypical). There was no correlation between the diameter of the primary tumour
      and the presence of nodal involvement. In particular, three of eight peripheral
      lesions <30 mm were found to have metastatic lymph nodes. The 5-year survival was
      92% (95% in N0 versus 56% in N1-2; 92% in typical versus 67% in atypical). The 10
      year survival was 84%. CONCLUSION: The specific diagnosis of atypical carcinoid
      cannot be reliably made on bronchial biopsies. No relationship was found between
      tumour size and the presence of lymph node metastases, suggesting that radical
      excision with detailed lymph node sampling is as important in carcinoids as in
      other lung cancers. Long-term survival was excellent, nodal status and pathology
      (typical/atypical) were independent prognostic factors.

PMID- 14698536
TI  - Association of macrophages, mast cells and eosinophil leukocytes with
      angiogenesis and tumor stage in non-small cell lung carcinomas (NSCLC).
AB  - The association between inflammatory cells, including tumor associated macrophage
      (TAM), mast cell (MC) and eosinophil leucocyte (EL) densities and angiogenesis,
      as well as the relation of TAM, MC and EL densities and angiogenesis to tumor
      stage were investigated in specimens of 63 non-small cell lung carcinoma (NSCLC).
      Fifteen cases were in stage I, 12 were in stage II, 33 were in stage III and 3
      were in stage IV. ELs and MCs were identified by hematoxilen-eosin and toluidine
      blue histochemical stains, respectively. TAMs were shown by immunohistochemistry
      for CD68. Microvessels demonstrated by immunohistochemistry for CD31 were
      quantified by a stereological method and vascular surface density (VSD) and
      microvessel number (NVES) were calculated. There was not any statistically
      significant correlation between tumor's stage and VSD, TAM and EL counts. MC
      count and NVES were found to be higher in early stages. VSD and NVES were not
      associated with EL, MC and TAM counts. The lack of consistent correlation of
      angiogenesis to the stage of disease in this study supports the view that tumor
      angiogenesis is not a significant prognostic factor in NSCLCs. The absence of
      correlation between MCs, ELs and TAM counts and angiogenesis and absence of any
      relation between ELs and TAMs and tumor stage are discordant with the results of
      some of the previous studies in NSCLCs and in other tumors. The differing results
      may be due to wide variations in methodologies which were used for demonstration
      of inflammatory cells and vessels and variations in the degree of activation and
      complexity of functions of these cells.

PMID- 14698537
TI  - Serum VEGF and bFGF adds prognostic information in patients with normal platelet
      counts when sampled before, during and after treatment for locally advanced non
      small cell lung cancer.
AB  - Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor
      (bFGF) have both been implicated to have roles in tumour angiogenesis. In the
      present retrospective study, serum VEGF and bFGF from patients with locally
      advanced non-small cell lung cancer (NSCLC) were analysed before, during and
      after treatment. Seventy-three patients and a total of 460 serum samples were
      analysed for VEGF and 443 serum samples were analysed for bFGF. Pre-treatment
      bFGF levels in patients with normal platelet counts, were correlated to poorer
      survival, P-value = 0.047. During chemotherapy, each rise of one unit bFGF
      corresponded to a hazard ratio of 4.06 (P=0.022). In patients with normal
      platelet counts, VEGF levels after radiotherapy significantly correlated to good
      prognosis (P=0.023), during radiotherapy VEGF levels indicated the same
      correlation (P=0.085). We conclude that serum VEGF and especially bFGF are of
      clinical interest as prognostic factors, especially in patients presenting with
      normal platelet counts.

PMID- 14698538
TI  - Inadequacy of the RECIST criteria for response evaluation in patients with
      malignant pleural mesothelioma.
AB  - The newly introduced Response Evaluation Criteria in Solid Tumors (RECIST), which
      relies on a single largest dimension of tumor rather than on the product of
      perpendicular diameters World Health Organisation (WHO) is intended to simplify
      the assessment of tumor response. PURPOSE: Is to evaluate the performance and
      validity of the RECIST compared to the WHO criteria. DESIGN: Thirty-four
      consecutive patients with bidimensionally measurable malignant pleural
      mesothelioma (MPM) were evaluated prospectively. RESULTS: In 27% (9/34) a
      discrepancy was found between the WHO and RECIST response evaluation 9% (3/34)
      concerned best responses and 18% (6/34) objective confirmed responses. In 24%
      (8/34) disease progression was missed by RECIST. The percentage of patients in
      whom one or more discordance's between WHO and RECIST were detected was 47, 88%
      due to underscoring by RECIST. In a subgroup of 24 MPM patients with
      bidimensionally measurable pleural lesions only, the discrepancy rate was 29%,
      always due to underscoring by RECIST. However, when in the same subgroup the
      modified RECIST response evaluation was used the discrepancy rate was 21% and in
      all cases due to underscoring by WHO. CONCLUSION: For MPM bidimensional WHO
      response evaluation cannot automatically be replaced by RECIST because MPM has a
      non-spherical growth pattern. Our recommendation is to use the WHO criteria for
      bidimensional measurable lesions, RECIST for unidimensional measurable lesions
      and a modified RECIST response evaluation, in which the short axis perpendicular
      to the chest wall is used, for thickened pleural rind disease, according to the
      method used in the recently completed pemetrexed (Alimta) trial for MPM.

PMID- 14698539
TI  - Inadequacy of the new Response Evaluation Criteria in Solid Tumors (RECIST) in
      patients with malignant pleural mesothelioma: report of four cases.
AB  - Unidimensional Response Evaluation Criteria in Solid Tumor (RECIST) has been
      recently proposed in the attempt to simplify the standardized bidimensional World
      Health Organization (WHO) criteria. The complete accord between these two
      measurement systems was established in a large comparative study [J. Natl. Cancer
      Inst. 92(3) (2000) 205] that demonstrated the validity and the good performance
      of RECIST criteria. We report four cases of inadequacy of RECIST criteria in the
      evaluation of response to chemotherapy in patients with malignant pleural
      mesothelioma. These four patients were enrolled in two consecutive multicenter
      phase II clinical trials investigating the activity of a novel chemotherapy
      regimen in advanced pleural mesothelioma. They were judged as having an objective
      response to chemotherapy according to WHO criteria. Reassessed according to both
      methods, we found that results obtained with RECIST criteria do not correspond to
      WHO underestimating response to chemotherapy. Our data raise doubts about the
      applicability of unidimensional RECIST response criteria to mesothelioma and,
      possibly, to any tumor involving the chest wall.

PMID- 14698540
TI  - Staging and evaluating responses in malignant pleural mesothelioma.

PMID- 14698541
TI  - Photodynamic therapy for peripheral lung cancer.
AB  - Photodynamic therapy (PDT) has now achieved the status of a standard treatment
      modality for centrally located early-stage lung cancer. In the last decade, CT
      screening for lung cancer has attracted much attention for its ability to detect
      early peripheral lung cancer. Extremely recently, treatment using PDT has been
      introduced for the first time in patients with peripheral lung cancer, who did
      not meet the previous criteria for surgery. The procedure was carried out with
      local anesthesia with xylocain infiltrated into the chest wall, 48 h after
      Photofrin administration. Needles (19 gauge) containing an internal catheter were
      inserted percutaneously under CT guidance. The needles were then extracted and a
      diffuser fiber with a 2 cm long tip for light delivery was positioned in the
      tumor through the catheter. Of the nine patients enrolled in this trial, seven
      achieved partial remission (PR). No serious complications, except for two cases
      of pneumothorax, were noted. As an increasing number of patients consider quality
      of life after therapy, the indications for PDT are expected to expand. We
      conclude that PDT is a promising new technique for curative treatment of
      localized, peripheral lung cancer less than 1cm in size in patients who are unfit
      for surgery or radiotherapy.

PMID- 14698542
TI  - Cisplatin versus carboplatin in combination with mitomycin and vinblastine in
      advanced non small cell lung cancer. A multicenter, randomized phase III trial.
AB  - BACKGROUND: In advanced not selected NSCLC chemotherapy achieved an advantage of
      approximately 1-2 months on median survival versus best supportive care.
      Chemotherapy seems to improve symptoms control, even if randomised studies with
      quality of life as first endpoint are lacking and often chemotherapy toxicity
      compromises the frail cost/benefit ratio. The aim of the present study is to
      evaluate the impact on QoL, substituting cisplatin, a pivot drug in NSCLC
      therapy, with carboplatin, an analogue with an improved toxicity profile. The
      combination of cisplatin with Mitomycin and Vinblastine was one of the most
      frequently used in the palliative setting at the time of design of our study.
      METHODS: Patients were randomized to receive MVP regimen (Mitomycin-C 8 mg/m2 d1,
      Vinblastine 4 mg/m2 d 1-8, Cisplatin 100 mg/m2 d1) or MVC regimen (Mitomycin-C 8
      mg/m2 d1, Vinblastine 4 mg/m2 d 1-8, Carboplatin 300 mg/m2 d1) every 3 weeks. The
      QoL was evaluated by the Spitzer QL-Index and by the EORTC QLQ-C30+LC 13
      questionnaires before chemotherapy, after one cycle, after three cycles, and then
      every 6 weeks in the first 6 months and every 3 months thenafter. RESULTS: From
      September 1994 to July 1997, 153 consecutive patients were randomized to MVP (75
      patients) or MVC arm (78 patients). Despite difficulties in carrying out and
      analysing QoL items in such patients, the global QoL evaluated by the Spitzer's
      questionnaire suggested an advantage for MVC regimen (P=0.05) and a significant
      difference was observed in global health subdomain (P=0.04). The disease-related
      symptoms improved with time, and the benefits lasted for the entire treatment
      period. When evaluated with the EORTC questionnaire there was significantly less
      nausea and vomiting (P=0.0001), appetite loss (P=0.01), insomnia (P=0.03),
      constipation (P=0.01) and peripheral neuropathy (P=0.01) in favour of MVC, and a
      trend for less hair loss (P=0.05). The advantage lasted for all the duration of
      chemotherapy. No differences were observed in global quality of life subdomain
      (P=0.40) between the two regimen. QoL was the first endpoint and the statistical
      power was inadequate to assess other parameters. However, we reported a response
      rate of 43.1 and 38.6%, respectively, in MVP and MVC arm (P=0.59) and a median
      survival of 10.2 and 7.2 months, respectively, for cisplatin and carboplatin arm
      (P=0.39). CONCLUSIONS: The carboplatin containing regimen (MVC) has a significant
      better toxicity profile than the cisplatin containing (MVP) regimen as proven
      both by the EORTC questionnaires and by the WHO toxicity data reported by
      physicians. No significant differences in terms of response rate, time to
      progression and overall survival were observed between the two regimen. The two
      chemotherapy regimen showed a similar effectiveness in symptom palliation when
      evaluated with C30 addendum of EORTC QOL questionnaire. With the Spitzer's
      questionnaires a trend towards an improved quality of life index was observed
      during treatment with the carboplatin combination in comparison to the cisplatin
      combination. This difference, however, was not observed when the global quality
      of life was evaluated with the EORTC patients compiled questionnaires. A
      carboplatin containing regimen with better toxicity profile and a similar
      potentiality for symptoms control offers an option in comparison to similar
      cisplatin containing combinations in the palliative treatment of advanced NSCLC.

PMID- 14698544
TI  - Retrospective cost analysis of gemcitabine in combination with cisplatin in non
      small cell lung cancer compared to other combination therapies in Europe.
AB  - In two recent randomised trials, gemcitabine plus cisplatin (Gem/Cis) was found
      to be at least as effective as vinorelbine plus cisplatin (Vin/Cis), paclitaxel
      plus cisplatin (Pac/Cis), paclitaxel plus carboplatin (Pac/Carbo), or docetaxel
      plus cisplatin (Doc/Cis) in patients with advanced non-small cell lung cancer
      (NSCLC). In cost-minimisation analyses of these studies from the perspectives of
      the national health services of five European countries (France, Germany, Italy,
      Spain, UK), Gem/Cis was associated with lower average treatment-related costs
      than Vin/Cis, Pac/Cis, and Pac/Carbo, and similar or lower costs than Doc/Cis.
      The incremental cost savings per patient of Gem/Cis compared to Vin/Cis ranged
      from 827 Euro to 2055 Euro per patient and from 1616 Euro to 5342 Euro compared
      to the paclitaxel-containing regimens. Overall, results were generally similar
      between countries, and were robust to univariate sensitivity analyses. Although
      differences in healthcare systems mean that the results may not be generalisable
      to all countries/settings, these results provide an economic rationale for the
      use of Gem/Cis as a first-line treatment option in Europe for patients with
      NSCLC.

PMID- 14698543
TI  - Combination chemotherapy of gemcitabine and vinorelbine for patients in stage
      IIIB-IV non-small cell lung cancer: a phase II study of the West Japan Thoracic
      Oncology Group (WJTOG) 9908.
AB  - OBJECTIVES: Vinorelbine (V) and gemcitabine (G) are two active single agents used
      in the treatment of non-small cell lung cancer (NSCLC). A multicenter clinical
      trial (West Japan Thoracic Oncology Group (WJTOG) 9908) was conducted to evaluate
      the efficacy and toxicity of V and G in patients (pts) with advanced NSCLC.
      METHODS:  ELIGIBILITY CRITERIA: no previous chemotherapy; performance status (PS)
      0 or 1; age <75 years old. V, 25mg/m2, was given as a 2-3 min IV infusion,
      followed by a 30 min IV infusion of G, 1000 mg/m2, on days 1 and 8 of each 21-day
      cycle. RESULTS: From April 2000 to September 2000, 52 pts were enrolled in the
      study. Two pts were ineligible. Baseline characteristics: median age 60, males 30
      (60%), Eastern Cooperative Oncology Group (ECOG) PS 0/1=21/29 (58%), stage
      IIIB/IV=12/38 (76%), adenocarcinoma=35 (70%). The median number of cycles
      administered was 2. Fifty pts were evaluable for response. The response rate was
      18% by the Response Evaluation Criteria in Solid Tumors (RECIST) (no complete
      response (CR), 9 partial response (PR), 25 stable disease, 12 progressive
      disease, 4 not evaluable). Grade III/IV toxicities were as follows: neutropenia
      grade III/IV=66%, anemia grade III/IV=16%, thrombocytopenia grade III/IV=2%,
      nausea grade III/IV=10%, vomiting grade III/IV=0%, documented infection grade
      III/IV=10%, skin rash grade III/IV=2%, and hepatic grade III/IV=8%. There were no
      treatment-related deaths. The median time to progression was 4.1 months. The
      overall median survival time (MST) was 13.9 months (range, 2.4 to >16.2 months)
      with a median follow-up time of 13.9 months. The MST for stage IIIB and stage IV
      was >14.5 and 12.7 months, respectively. The overall estimated 1-year survival
      rate was 55.4%. CONCLUSIONS: This regimen has modest activity and is very well
      tolerated, with an encouraging 1-year survival rate.

PMID- 14698545
TI  - Taking ACTION to establish direct costs and outcomes of treating advanced non
      small cell lung cancer in routine clinical practice.

PMID- 14698546
TI  - Reply to "Radiation pneumonitis and docetaxel".

PMID- 14698549
TI  - Characterization of acylphosphatidylglycerols from Salmonella typhimurium by
      tandem mass spectrometry with electrospray ionization.
AB  - Acylphosphatidylglycerol (Acyl-PG), a polar lipid class containing three fatty
      acyl groups, was isolated from Salmonella bacteria and characterized by tandem
      quadrupole and quadrupole ion-trap mass spectrometric methods with electrospray
      ionization. The structural characterization of the acyl-PG with various acyl
      groups (A-B/C-PG, where A not equal B not equal C) is based on the findings that
      the carboxylate anions (R(x)CO(2)(-)) arising from sn-2 (R(2)CO(2)(-)) is more
      abundant than that arising from sn-3' (R(3')CO(2)(-)), which is much more
      abundant than that arising from sn-1 (R(1)CO(2)(-)). This information provides a
      simple method for determination of the fatty acyl moieties and their positions in
      the molecule. The structural identification of the molecule can also be achieved
      by the findings that the fragment ion reflecting the ketene loss at sn-2 is more
      prominent than that reflecting the acid loss (i.e., [M - H - R'(2)CH=CO](-) > [M 
      H - R(2)CO(2)H](-)), while the ion arising from acid loss at sn-1 or sn-3' is,
      respectively, more abundant than the corresponding ketene loss (i.e., [M - H -
      R(1)CO(2)H](-) > [M - H - R'(1)CH=CO](-); [M - H - R(3')CO(2)H](-) > [M - H 
      R'(3')CH=CO](-)). The identity of the acyl moiety at sn-3' can be confirmed by an
      acyl-glycerophosphate anion observed in the product-ion spectrum obtained with a
      triple-stage quadrupole (TSQ) instrument, but not in that obtained with an ion
      trap mass spectrometer (ITMS). However, the MS(2)-spectrum obtained with an ITMS
      is featured by the ion series that abundances of [M - H - R'(2)CH=CO - R(3)CO(2)H
      - 74](-) > [M - H - R'(2)CH=CO - R(1)CO(2)H - 74](-) z.Gt; [M - H - R'(1(or
      3'))CH=CO - R(3'(or 1))CO(2)H - 74](-). This information also facilitates
      structural elucidation of the acyl-PG subclass that contains various acyl
      substituents. Structural identifications of molecular species having two
      identical fatty acyl substituents at sn-1, sn-2, or sn-3' or consisting of more
      than one isomeric structures are also demonstrated. The identities of the minor
      isomeric species in the molecules can be revealed by the aforementioned
      structural information arising from the various ion series combined.

PMID- 14698550
TI  - Isotopic compositions and accurate masses of single isotopic peaks.
AB  - This paper presents and proves an algorithm to calculate the isotopic composition
      of individual (nominal) isotopic peaks. From this information one can calculate
      the accurate masses of isotopic peaks. This opens the way to use accurate mass
      measurements to determine chemical compositions of compounds using non-mono
      isotopic peaks. The algorithm is computationally efficient and rigorously correct
      in the absence of roundoff error. Highly effective error correction strategies
      are described to detect and correct computational errors arising in practical
      calculations. Results from theoretical calculations of isotopic masses for a
      krypton inclusion complex agreed well with experimental measurements.

PMID- 14698551
TI  - An electrospray ionization mass spectrometric study of the subunit structure of
      the giant hemoglobin from the leech Nephelopsis oscura.
AB  - The subunit structure of the giant, extracellular hexagonal bilayer (HBL)
      hemoglobin (Hb) from the leech Nephelopsis oscura was investigated by
      electrospray ionization mass spectrometry (ESI-MS) employing a maximum entropy
      deconvolution of its complex, multiply charged ESI spectra. The denatured
      unreduced Hb consisted of three monomer globin chains (M), a1 = 16535 Da, a2 =
      17171 Da and a3 = 17315 Da, five nonglobin linker chains, L1 = 24512 Da, L2 =
      24586 Da, L3 = 24979 Da, L4 = 25006 Da, and L5 = 25566 Da and two subunits of
      32950 Da and 33125 Da. ESI-MS of the denatured, reduced Hb showed that the latter
      were disulfide-bonded heterodimers (D) of globin chains b1 = 16322 Da and b2 =
      16499 Da with chain c = 16632 Da. Time-of-flight ESI-MS of the Hb at pH 3.8, 4.5,
      5.0, 5.8 and 7.0 revealed a distribution of charge states from 32(+) to 37(+)
      with masses decreasing from 211 to 208.5 kDa with increase in cone voltage from
      60 to 160 V, indicating the presence of a subassembly comprising 12 globin
      chains. The subunit composition 6M + 3D + 12h, where M = 16993 Da and D = 33004
      Da are the weighted masses and h = 616.5 Da, provides a calculated mass, 208.37
      kDa that is closest to 208.5 kDa. Our experimental findings are consistent with
      the bracelet model of HBL Hbs, verified by the recent low-resolution crystal
      structure of Lumbricus Hb, wherein an HBL arrangement of 12 globin dodecamer
      subassemblies is tethered to a central complex of 36 linker chains for a total
      mass of 208.37 x 12 + 24.94 x 36 = 3398 kDa.

PMID- 14698552
TI  - Detection of specific noncovalent interaction of peptide with DNA by MALDI-TOF.
AB  - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry was used to
      obtain spectra of peptide-DNA complexes formed by basic domain (BD15) of c-Fos
      protein and DNA AP-1 site (5'-TGAGTCA-3'). The noncovalent interaction between
      single stranded DNA and BD15 was observed and confirmed to be an ionic one
      between the negatively charged sugar-phosphate backbone of DNA and positively
      charged side chains of Arg- and lys-rich peptides as demonstrated by Vertes and
      coworkers and Woods and coworkers. But the specific noncovalent interaction
      between DNA AP-1 site and the dimer of BD15 was firstly detected in this paper.
      Various different sequence DNAs were studied and it was found that this
      interaction is a sequence-specific one, and AP-1 site was essential for this
      interaction. This specific interaction depends on the matrix. It was only
      observed in the ATT matrix and not in the other two matrixes (CHCA and DHBA).

PMID- 14698553
TI  - Automated de novo sequencing of nucleic acids by liquid chromatography-tandem
      mass spectrometry.
AB  - We present the first global computer-aided sequencing algorithm for the de novo
      determination of short nucleic acid sequences. The method compares the fragment
      ion spectra generated by collision-induced dissociation of multiply charged
      oligodeoxynucleotide-ions to the m/z values predicted employing established
      fragmentation pathways from a known reference sequence. The closeness of matching
      between the measured spectrum and the predicted set of fragment ions is
      characterized by the fitness, which takes into account the difference between
      measured and predicted m/z values, the intensity of the fragment ions, the number
      of fragments assigned, and the number of nucleotide positions not covered by
      fragment ions in the experimental spectrum. Smaller values for the fitness
      indicate a closer match between the measured spectrum and predicted m/z values.
      In order to find the sequence most closely matching the experimental spectrum,
      starting from a given nucleotide composition all possible oligonucleotide
      sequences are assembled followed by identification of the correct sequence by the
      lowest fitness value. Using this concept, sequences of 5- to 12-mer
      oligodeoxynucleotides were successfully de novo determined. High sequence
      coverage with fragment ions was essential for obtaining unequivocal sequencing
      results. Moreover, the collision energy was shown to have an impact on the
      interpretability of tandem mass spectra by the de novo sequencing algorithm.
      Experiments revealed that the optimal collision energy should be set to a value
      just sufficient for complete fragmentation of the precursor ion.

PMID- 14698554
TI  - Structural differentiation of uronosyl substitution patterns in acidic
      heteroxylans by electrospray tandem mass spectrometry.
AB  - The structures of two oligomers of acidic xylo-oligosaccharides (XOS) of the same
      molecular weight (634 Da), Xyl(2)MeGlcAHex and Xyl(2)GlcA(2) were differentiated
      by electrospray tandem mass spectrometry (ESI-MS/MS). These oligomers were
      present in a mixture of XOS obtained by acid hydrolysis of heteroxylans extracted
      from Eucalyptus globulus wood (Xyl(2)MeGlcAHex) and Olea europaea olive fruit
      (Xyl(2)GlcA(2)). In the ESI-MS spectra of the XOS, ions at m/z 657 and 652 were
      observed and assigned to [M + Na](+) and [M + NH(4)](+), respectively. The ESI
      MS/MS spectrum of [M + Na](+) ion of Xyl(2)MeGlcAHex showed the loss of Hex
      residue from the reducing end followed by the loss of MeGlcA moiety.
      Simultaneously, the loss of a Xyl residue from either the reducing or the non
      reducing ends was detected. On the other hand, the fragmentation of Xyl(2)GlcA(2)
      occurs mainly by the loss of one and two GlcA residues or by the loss of the
      GlcAXyl moiety, due to the glycosidic bond cleavage between the two Xyl residues.
      Loss of one and two CO(2) molecules was only observed for this oligomer, where
      the GlcA are in vicinal Xyl residues. The ESI-MS/MS spectra of [M + NH(4)](+) of
      both oligomers showed the loss of NH(3), resulting in the protonated molecule,
      where the presence of ions assigned as protonated molecules of aldobiuronic acid
      residues, [MeGlcA - Xyl + H](+) and [GlcA - Xyl + H](+), are diagnostic ions of
      the presence of MeGlcA and GlcA moieties in XOS. Since these structures occur in
      small amounts in complex acidic XOS mixtures and are very difficult, if possible,
      to isolate, tandem mass spectrometry revealed to be a powerful tool for the
      characterization of these types of substitution patterns present in heteroxylans.

PMID- 14698555
TI  - Ion energy in quadrupole mass spectrometry.
AB  - Application of an analytical solution of the Mathieu equation in conjunction with
      algebraic presentation of the Mathieu functions for description of the ion energy
      in a radiofrequency quadrupole field is discussed in this work. The analytical
      approach is used to express the ion energy averaged over the initial ion velocity
      distribution function, field phase and ion residence time. Comparisons with the
      approximate solutions for potential ion energy are presented with demonstration
      of their limits. Application of the method for different stability regions is
      discussed.

PMID- 14698556
TI  - Arrhenius activation parameters for the loss of neutral nucleobases from
      deprotonated oligonucleotide anions in the gas phase.
AB  - Arrhenius activation parameters (E(a) and A) for the loss of neutral nucleobase
      from a series of doubly deprotonated oligodexoynucleotide 10-mers of the type
      XT(9), T(9)X, and T(5)XT(4), where X = A, C, and G, have been determined using
      the blackbody infrared radiative dissociation technique. At temperatures of 120
      to 190 degrees C, the anions dissociate exclusively by the loss of a neutral
      nucleobase (XH), followed by cleavage of the sugar 3' C-O bond leading to (a-XH)
      and w type ions or, in the case of the T(9)X(2-) ions, the loss of H(2)O. The
      dissociation kinetics and energetics are sensitive to the nature and position of
      X. Over the temperature range investigated, the kinetics for the loss of AH and
      GH were similar, but approximately 100 times faster than for the loss of CH. For
      the loss of AH and GH, the values of E(a) are sensitive to the position of the
      base. The order of the E(a)s for the loss of XH from the 5' and 3' termini is: C
      > G > A; while for T(5)XT(4) the order is: C > A > G. The trends in the values of
      E(a) do not parallel the trend in deprotonation enthalpies or proton affinities
      of the nucleobases in the gas phase, indicating that the energetic differences do
      not simply reflect differences in their gas phase acidity or basicity. The pre
      exponential factors (A) vary from 10(10) to 10(15) s(-1), depending on the nature
      and position of X. These results suggest that the reactivity of individual
      nucleobases is influenced by stabilizing intramolecular interactions.

PMID- 14698557
TI  - Gas-phase reactions of protonated tryptophan.
AB  - The gas phase reactions of protonated tryptophan have been examined in a
      quadrupole ion trap using a combination of collision induced dissociation,
      hydrogen-deuterium exchange, regiospecific deuterium labeling and molecular
      orbital calculations (at the B3LYP/6-31G* level of theory). The loss of ammonia
      from protonated tryptophan is observed as the primary fragmentation pathway, with
      concomitant formation of a [M + H - NH(3)](+) ion by nucleophilic attack from the
      C3 position of the indole side chain. Hydrogen-deuterium exchange and
      regiospecific deuterium labeling reveals that scrambling of protons in the C2 and
      C4 positions of the indole ring, via intramolecular proton transfer from the
      thermodynamically preferred site of protonation at the amino nitrogen, precedes
      ammonia loss. Molecular orbital calculations have been employed to demonstrate
      that the activation barriers to intramolecular proton transfer are lower than
      that for NH(3) loss.

PMID- 14698558
TI  - Differential expression of histone post-translational modifications in acute
      myeloid and chronic lymphocytic leukemia determined by high-pressure liquid
      chromatography and mass spectrometry.
AB  - The post-translational modification of the core histones is critical to the
      regulation of chromatin structure. Traditional methods for the determination of
      histone modification utilize immunoassay techniques to determine the extent and
      site of post-translational modification. These methods, though sensitive, require
      site-specific antibodies. This manuscript describes the application of reverse
      phase high-pressure liquid chromatography and mass spectrometry (LC-MS) to
      analyze global modification levels of core histones. The method is fast,
      sensitive, and easily automated. Furthermore, the technique gives the global
      patterns of modification for all four core histones in a single experiment. The
      LC-MS method was optimized using histones extracted from bovine thymus. These
      methods were then applied to the characterization of changes in histone
      modification in acute myeloid leukemia (AML) cell lines treated with histone
      deacetylase (HDAC) inhibitors. Dose-dependent changes in the distribution of
      modified core histones were observed. These results were validated in primary
      leukemia cells from patients with refractory or relapsed AML or chronic
      lymphocytic leukemia (CLL) treated on a Phase I clinical trial of the HDAC
      inhibitor depsipeptide. An increase in the relative abundance of specific
      acetylated forms of histone H4 was readily observable in these patients at
      intervals of 4 and 24 h after treatment.

PMID- 14698559
TI  - Millisecond pulsed radio frequency glow discharge time of flight mass
      spectrometry: temporal and spatial variations in molecular energetics.
AB  - The internal energy distributions, P(epsilon), of a millisecond pulsed radio
      frequency glow discharge plasma were investigated using tungsten hexcarbonyl
      W(CO)(6) as a "thermometer molecule". Vapor of the probe molecule, W(CO)(6), was
      introduced into the plasma and subjected to various ionization and excitation
      processes therein. The resultant molecular and fragment ions were monitored using
      a Time-of-Flight mass spectrometer. Ion abundance data were utilized in
      combination with the known energetics of W(CO)(6) to construct the P(epsilon)
      plots. The P(epsilon) of W(CO)(6) exhibited strong temporal dependence over the
      pulse cycle: Distinct internal energy distributions were found at the discharge
      breakdown period (prepeak), the steady state period (plateau), and the post-pulse
      period (afterpeak). Spatial variation in P(epsilon) was also observed, especially
      during the plateau regime. The observations suggest that this pulsed glow
      discharge affords excellent energy tunability that can be used to perform
      selective ionization and fragmentation for molecular, structural, and elemental
      information. Parametric studies were performed to evaluate the effects of
      discharge pressure and operating power on P(epsilon). These studies also provided
      insight into the correlation of the observed P(epsilon)s with the fundamental
      ionization and excitation mechanisms in the plasma. The temporal and spatial
      variations in P(epsilon) were hence attributed to changes in the dominant energy
      transfer processes at specific times in specific regions of the plasma. These
      data will be useful in future efforts to optimize the analytical performance of
      this source for chemical speciation.

PMID- 14698560
TI  - Towards understanding the tandem mass spectra of protonated oligopeptides. 1:
      mechanism of amide bond cleavage.
AB  - The mechanism of the cleavage of protonated amide bonds of oligopeptides is
      discussed in detail exploring the major energetic, kinetic, and entropy factors
      that determine the accessibility of the b(x)-y(z) (Paizs, B.; Suhai, S. Rapid
      Commun. Mass Spectrom. 2002, 16, 375) and "diketopiperazine" (Cordero, M. M.;
      Houser, J. J.; Wesdemiotis, C. Anal. Chem. 1993, 65, 1594) pathways. General
      considerations indicate that under low-energy collision conditions the majority
      of the sequence ions of protonated oligopeptides are formed on the b(x)-y(z)
      pathways which are energetically, kinetically, and entropically accessible. This
      is due to the facts that (1).the corresponding reactive configurations (amide N
      protonated species) can easily be formed during ion excitation, (2). most of the
      protonated nitrogens are stabilized by nearby amide oxygens making the spatial
      arrangement of the two amide bonds (the protonated and its N-terminal neighbor)
      involved in oxazolone formation entropically favored. On the other hand,
      formation of y ions on the diketopiperazine pathways is either kinetically or
      energetically or entropically controlled. The energetic control is due to the
      significant ring strain of small cyclic peptides that are co-formed with y ions
      (truncated protonated peptides) similar in size to the original peptide. The
      entropy control precludes formation of y ions much smaller than the original
      peptide since the attacking N-terminal amino group can rarely get close to the
      protonated amide bond buried by amide oxygens. Modeling the b(x)-y(z) pathways of
      protonated pentaalanine leads for the first time to semi-quantitative
      understanding of the tandem mass spectra of a protonated oligopeptide. Both the
      amide nitrogen protonated structures (reactive configurations for the amide bond
      cleavage) and the corresponding b(x)-y(z) transition structures are energetically
      more favored if protonation occurs closer to the C-terminus, e.g., considering
      these points the Ala(4)-Ala(5) amide bond is more favored than Ala(3)-Ala(4), and
      Ala(3)-Ala(4) is more favored than Ala(2)-Ala(3). This fact explains the
      increasing ion abundances observed for the b(2)/y(3), b(3)/y(2), and b(4)/y(1)
      ion pairs in the metastable ion and low-energy collision induced mass spectra
      (Yalcin, T.; Csizmadia, I. G.; Peterson, M. B.; Harrison, A. G. J. Am. Soc. Mass
      Spectrom. 1996, 7, 233) of protonated pentaalanine. A linear free-energy
      relationship is used to approximate the ratio of the b(x) and y(z) ions on the
      particular b(x)-y(z) pathways. Applying the necessary proton affinities such
      considerations satisfactorily explain for example dominance of the b(4) ion over
      y(1) and the similar b(3) and y(2) ion intensities observed for the metastable
      ion and low-energy collision induced mass spectra.

PMID- 14698561
TI  - Reactions of diacetylene radical cation with ethylene.
AB  - Ion-molecule reactions and energy-resolved mass spectrometry have been used to
      determine the structures of the products formed in the reaction of diacetylene
      radical cation with ethylene in a flowing afterglow-triple quadrupole instrument.
      The structure of the adduct ion, C(6)H(6)(.+), has been determined to be that of
      singly ionized benzene. The reaction thus presents a first example of the ability
      of diacetylene radical cation to undergo an aromatic ring forming reaction. The
      other products formed in the reaction are m/z 52, C(4)H(4)(.+), and m/z 39,
      C(3)H(3)(+). Isotopic labeling studies show that C(4)H(4)(.+) and C(3)H(3)(+) are
      formed with nearly statistical hydrogen incorporation, indicating a complex
      mechanism that scrambles all protons.

PMID- 14698562
TI  - Determination of the relative energies of activation for the dissociation of
      aromatic versus aliphatic phosphopeptides by ESI-FTICR-MS and IRMPD.
AB  - Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (ESI-FTICR-MS)
      coupled with infrared multiphoton dissociation (IRMPD) is potentially a powerful
      method for rapid phosphopeptide mapping of complex proteolytic digests. The
      dissociation of deprotonated phosphopeptides by IRMPD is energetically favorable
      over unmodified deprotonated peptides because of a lower energy of activation and
      a higher internal energy under identical irradiation conditions. The energies of
      activation for dissociation are determined for model peptides phosphorylated on
      an aliphatic side chain (serine) and an aromatic side chain (tyrosine). The
      determination of phosphorylation location provides important biochemical
      information identifying the kinase involved in specific phosphorylation
      mechanisms. The data presented in this manuscript also support the theory that
      for phosphopeptides, the phosphate moiety's P-O stretch is in direct resonance
      with the infrared laser (10.6 microm), thus increasing the relative absorptivity
      of the modified species. A greater extinction coefficient affords more extensive
      photon absorption and subsequently a greater internal energy at the rapid
      exchange limit.

PMID- 14698563
TI  - A high pressure matrix-assisted laser desorption ion source for Fourier transform
      mass spectrometry designed to accommodate large targets with diverse surfaces.
AB  - A new design for a high pressure MALDI-FTMS instrument is described and initial
      data are shown. The instrument incorporates a large, 10 cm x 10 cm, sample
      translation stage to accommodate and position the MALDI target. The new
      instrument allows coupling to a wide variety of surface techniques such as gel
      electrophoresis or surface plasmon resonance. Coupling to thin layer
      chromatography is shown. Furthermore, a new nozzle design allows high pressure
      collisional cooling sufficient to stabilize gangliosides while minimizing the gas
      load on the system.

PMID- 14698564
TI  - Protein kinase C delta is activated in mouse ovarian surface epithelial cancer
      cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
AB  - Interactions between the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and protein
      kinase C (PKC) signaling pathways are governed in cell and tissue-specific
      manners, albeit the physiological significance of which is unclear. This research
      sought to define the effects of TCDD on the PKC pathway using a mouse ovarian
      surface epithelial cancer cell line (ID8). Phorbol-12-myristate-13-acetate (PMA)
      potentiated (1 nM) TCDD-induced 7-ethoxyresorufin-O-deethylase (EROD) activity
      after 24h of treatment, and pre-treatment with (1 microM) of either a general PKC
      inhibitor (BisI) or PKCdelta-specific inhibitor (Rotterlin) abolished the
      potentiation indicating that activation of PKC enhances TCDD signal transduction.
      Western blot analysis revealed that unstimulated ID8 cells express PKCalpha,
      beta, epsilon, tau, lambda and RACK1. PKCgamma, eta, theta and DGKtheta were not
      detected. TCDD (1 nM) increased PKCdelta protein approximately eight-fold after
      24h of treatment and this effect was dose-dependent (0.1-100 nM); other PKC
      isoforms and related signaling proteins tested were unaffected by TCDD treatment.
      Immunofluorescent microscopy revealed that TCDD (1 nM) promoted the subcellular
      redistribution of PKCdelta, from the cytoplasm and the nucleus to the perinuclear
      area after 2h of treatment, however, after 24h of treatment PKCdelta was observed
      in nuclear structures that resembled nucleoli. TCDD (1 nM) also increased total
      PKC and PKCdelta-specific kinase activities in biphasic time-responsive manners.
      Total PKC and PKCdelta-specific activities increased after 1-2h of treatment.
      Then TCDD increased the total PKC activity again after 12h of treatment, whereas,
      PKCdelta-specific activity resurged at 24h and remained elevated at 48 h after
      treatment. The results indicate that TCDD preferentially induces PKCdelta protein
      expression and phosphotransferase activity, and its membrane translocation,
      indicating a potential intracellular role for PKCdelta as an effector molecule
      for TCDD-mediated biological events in this ovarian cancer cell line.

PMID- 14698566
TI  - Chemical composition, cytotoxicity and mutagenicity of smoke from US commercial
      and reference cigarettes smoked under two sets of machine smoking conditions.
AB  - Eight blended US market cigarettes, two blended reference cigarettes, one Bright
      tobacco only reference cigarette and an electrically heated prototype cigarette
      (EHC) were smoked under US Federal Trade Commission (FTC)/International
      Organisation for Standardisation (ISO) conditions and under Massachusetts
      Department of Public Health (MDPH) conditions. Smoke was analysed for chemical
      composition and in vitro toxicity. Yields (quantity/cigarette) of smoke
      constituents were higher under MDPH conditions compared to FTC/ISO conditions
      (market and reference average approximately 2.5 times; EHC approximately 1.6
      times). Consistent with the higher yields, in vitro toxicity per cigarette was
      also higher under MDPH conditions. Concentrations (quantity/mg TPM) of nearly all
      smoke constituents measured decreased with increasing total particulate matter
      (TPM) yields as regression analyses indicated. Higher TPM yields also tended to
      be associated with slightly less cytotoxic and mutagenic activity per milligram
      TPM. Blended reference cigarettes tracked market cigarettes with similar TPM
      yield. The Bright cigarette displayed high cytotoxicity but low mutagenicity,
      while in vitro activity of the EHC was remarkably low. The TPM-dependent
      decreases for the market range of 5-20 mg TPM/cigarette were about 20%,
      irrespective of whether the increased yields were due to smoking conditions or
      cigarette construction. At the same TPM yield, the smoke constituent
      concentrations and in vitro toxicity were similar for low- and high-yield
      cigarettes.

PMID- 14698565
TI  - Exacerbation of benzene pneumotoxicity in connexin 32 knockout mice: enhanced
      proliferation of CYP2E1-immunoreactive alveolar epithelial cells.
AB  - The pulmonary pathogenesis triggered by benzene exposure was studied. Since the
      role of the connexin 32 (Cx32) gap junction protein in mouse pulmonary
      pathogenesis has been suggested, in the present study, we explored a possible
      role of Cx32 in benzene-induced pulmonary pathogenesis using the wild-type (WT)
      and Cx32 knockout (KO) mice. The mice were exposed to 300 ppm benzene by
      inhalation for 6 h per day, 5 days per week for a total of 26 weeks, and then
      sacrificed to evaluate the pneumotoxicity or allowed to live out their life span
      to evaluate the reversibility of the lesions and tumor incidence. Our results
      clearly revealed exacerbated pneumotoxicity in the benzene-exposed Cx32 KO mice,
      characterized by diffuse granulomatous interstitial pneumonia, markedly increased
      mucin secretion of bronchial/bronchiolar and alveolar epithelial cells, and
      hyperplastic alveolar epithelial cells positive for CYP2E1. But the results did
      not indicate any enhancement of pulmonary tumorigenesis in the Cx32 KO mice
      though the number of animals was small.

PMID- 14698567
TI  - Epigallocatechin 3-gallate attenuates neuronal damage induced by 3
      hydroxykynurenine.
AB  - 3-Hydroxykynurenine (3-HK), which is an endogenous metabolite of tryptophan in
      the kynurenine pathway, is a potential neurotoxin in several neurodegenerative
      disorders. Epigallocatechin 3-gallate (EGCG), a major compound of green tea, is
      recognized as a promising natural substance for protection against neuronal
      diseases. This study investigated the possible protective roles and mechanism of
      EGCG, against 3-HK-induced cell death. It was found that 3-HK induces neuronal
      cell death in the human neuroblastoma SH-SY5Y cell line. The reduced cell
      viability produced characteristic features such as cell shrinkages, plasma
      membrane blebbing, chromatin condensation, and nuclear fragmentation. The cells
      treated with 3-HK showed an increase in the concentration of reactive oxygen
      species (ROS) as well as in caspase activity. In addition, both are involved in
      the 3-HK-induced apoptosis. EGCG attenuated the cell viability reduction by 3-HK
      in both a dose- and time-dependent manner. Optical microscopy showed that EGCG
      inhibited the cell morphological features in the 3-HK-treated cells. Furthermore,
      the increase in the ROS concentration and the caspase activities by 3-HK were
      also attenuated by EGCG. These results showed that EGCG has a protective effect
      on the 3-HK induced cell death by inhibiting ROS production and caspase activity.
      The results suggest that EGCG might be a promising protective substance against
      the neuronal degenerative diseases.

PMID- 14698568
TI  - A recombinant model for assessing the role of GSTM1 in styrene-7,8-oxide toxicity
      and mutagenicity.
AB  - Styrene-7,8-oxide (SO) is a highly reactive epoxide able to undergo reactions
      with endogenous nucleophiles, such as DNA. SO is inactivated by glutathione-S
      transferase M1 (GSTM1). This detoxification enzyme is absent in approximately one
      half of Caucasian (49%) populations. A GSTM1 recombinant human lymphoblastoid
      cell line (FB7) was generated from a GSTM1 negative parental cell line (WIL2NS).
      GSTM1 status was determined using RT-PCR and immunochemistry. Cells were
      challenged with a range of SO doses and subsequent toxicity (population growth in
      flasks) and genotoxicity (mutations at the HPRT locus) were monitored. FB7 (GSTM1
      positive) exhibited greater cell survival after SO exposure relative to the GSTM1
      negative parental line. The IC50 following a 1 h exposure to SO was 0.5 mM for
      WIL2NS, compared to greater than 2.5 mM for FB7. The extrapolated IC50 for FB7
      was 5.5 mM. Significantly fewer mutant cells were induced by SO for FB7 than for
      WIL2NS at equivalent doses of SO. These findings suggest that the sensitivity of
      cells to styrene-7,8-oxide is influenced by GSTM1 status and that a recombinant
      GSTM1 positive cell line can efficiently detoxify styrene-7,8-oxide.

PMID- 14698569
TI  - Opposite effects of zinc and melatonin on thyroid hormones in rats.
AB  - The present study was conducted to investigate how thyroid function in rats is
      affected by administration of 3 mg per kg per day of zinc and/or melatonin. The
      study was conducted with 40 Sprague-Dawley adult male rats equally divided into
      four groups: 1 (controls), 2 (zinc-only), 3 (melatonin-only) and 4 (zinc- and
      melatonin-supplemented). The supplementation was continued for 4 weeks after
      which the animals were sacrificed and plasma samples were obtained for
      determination of zinc, melatonin, free- and total triiodothyronine (T3),
      thyroxine (T4) and thyroid-stimulating hormone (TSH) levels. The free T3, T4 and
      TSH levels were lower in the melatonin group than in all other groups (P<0.01),
      while free- and total T3 levels were higher in the zinc group (P<0.01). The group
      that received zinc and melatonin combined had free thyroid hormone levels higher
      than the only melatonin group. These results show that melatonin has a thyroid
      function suppressing action, just the opposite to the actions of zinc. When zinc
      is administered along with melatonin, its thyroid function suppression is
      diminished.

PMID- 14698570
TI  - Effect of thimerosal, a preservative in vaccines, on intracellular Ca2+
      concentration of rat cerebellar neurons.
AB  - The effect of thimerosal, an organomercurial preservative in vaccines, on
      cerebellar neurons dissociated from 2-week-old rats was compared with those of
      methylmercury using a flow cytometer with appropriate fluorescent dyes.
      Thimerosal and methylmercury at concentrations ranging from 0.3 to 10 microM
      increased the intracellular concentration of Ca2+ ([Ca2+]i) in a concentration
      dependent manner. The potency of 10 microM thimerosal to increase the [Ca2+]i was
      less than that of 10 microM methylmercury. Their effects on the [Ca2+]i were
      greatly attenuated, but not completely suppressed, under external Ca(2+)-free
      condition, suggesting a possibility that both agents increase membrane Ca2+
      permeability and release Ca2+ from intracellular calcium stores. The effect of 10
      microM thimerosal was not affected by simultaneous application of 30 microM L
      cysteine whereas that of 10 microM methylmercury was significantly suppressed.
      The potency of thimerosal was similar to that of methylmercury in the presence of
      L-cysteine. Both agents at 1 microM or more similarly decreased the cellular
      content of glutathione in a concentration-dependent manner, suggesting an
      increase in oxidative stress. Results indicate that thimerosal exerts some
      cytotoxic actions on cerebellar granule neurons dissociated from 2-week-old rats
      and its potency is almost similar to that of methylmercury.

PMID- 14698572
TI  - Solid state study of hydrogen bonding in dichlorophen crystals.
AB  - An X-ray crystallographic study of dichlorophen has been performed.
      Intramolecular hydrogen bonding is found within the molecule and intermolecular
      hydrogen bonding is present between molecules. The formation of dimers within the
      crystal lattice has been established.

PMID- 14698571
TI  - Vesicular systems in ocular drug delivery: an overview.
AB  - The main aim of pharmacotherapeutics is the attainment of effective drug
      concentration at the intended site of action for a sufficient period of time to
      elicit a response. Poor bioavailability of drugs from ocular dosage form is
      mainly due to the tear production, non-productive absorption, transient residence
      time, and impermeability of corneal epithelium. Though the topical and localized
      application are still an acceptable and preferred way to achieve therapeutic
      level of drugs used to treat ocular disorders but the primitive ophthalmic
      solution, suspension, and ointment dosage form are no longer sufficient to combat
      various ocular diseases. This article reviews the constraints with conventional
      ocular therapy and explores various novel approaches, in general, to improve
      ocular bioavailability of the drugs, advantages of vesicular approach over these
      and the future challenges to render the vesicular system more effective.

PMID- 14698573
TI  - V-blender segregation patterns for free-flowing materials: effects of blender
      capacity and fill level.
AB  - Stable segregation patterns are shown to form in V-blenders over a wide range of
      vessel capacities, fill levels, and rotation rates. Slight changes in either
      rotation rate or fill level induce changes in pattern formation. Trajectory
      segregation in two regions of the flow, accumulating over many flow periods,
      drives segregation pattern formation. Scaling criteria derived to relate particle
      velocities to vessel size and rotation rate in rotating cylinders successfully
      predict the rotation rate for the transition between patterns across V-blenders
      of 0.8-26.5 quart total capacity. This agreement suggests that pattern formation
      is governed by the magnitude of particle velocities. Regardless of vessel size,
      when particle velocities at specific regions of the blender are below a certain
      value, one particular pattern appears, and when they increase beyond that speed
      (i.e. by changing the rotation rate or the vessel size), a different pattern
      emerges. A scaling relation between segregation pattern formation and blender
      fill level was not identified because the complex flow patterns in the V-blender
      (the length of the flowing layer and the mixture center of mass relative to the
      blender are constantly oscillating) preclude the determination of a relationship
      between blender fill level and particle velocities.

PMID- 14698574
TI  - Percutaneous absorption of drugs used in atopic eczema: pimecrolimus permeates
      less through skin than corticosteroids and tacrolimus.
AB  - For treatment of skin diseases with topical drugs, penetration of the agents into
      the relevant layers of the skin is required. Permeation through the skin should,
      however, be kept to a minimum, in order to avoid the risk of systemic side
      effects. Here we compared the in vitro skin penetration and permeation of two
      novel drugs used in the therapy of atopic eczema (pimecrolimus and tacrolimus)
      and three representative corticosteroids (betamethasone-17-valerate, clobetasol
      17-propionate, and diflucortolon-21-valerate). Drug concentrations of
      pimecrolimus and corticosteroids in human skin were found to be in the same order
      of magnitude. Permeation of pimecrolimus through human skin was, however, lower
      by factors of 70-110 as compared to the steroids. When pimecrolimus was compared
      with tacrolimus in human, pig, or rat skin, similar concentrations of the two
      compounds were measured in the skin, whereas permeation of pimecrolimus through
      skin was consistently lower by factors of 9-10. Lipophilicity was found to be
      highest for pimecrolimus, its octanol-water distribution coefficient being higher
      by factors of 8 and 25-450 than that of tacrolimus and the corticosteroids,
      respectively. The low permeation of pimecrolimus may be explained by its higher
      lipophilicity (compared to tacrolimus and the corticosteroids) and higher
      molecular weight (compared to steroids). In conclusion, pimecrolimus appears to
      have a favourable skin penetration/permeation profile, featuring a low degree of
      percutaneous absorption.

PMID- 14698575
TI  - Design of liposomal aerosols for improved delivery of rifampicin to alveolar
      macrophages.
AB  - The present study was aimed at preparation, characterization, and performance
      evaluation of rifampicin-loaded aerosolized liposomes for their selective
      presentation to alveolar macrophages, that being the most dense site of
      tuberculosis infection. Egg phosphatidylcholine (PC)- and cholesterol (Chol)
      based liposomes were modified by imparting negative charge (using
      dicetylphosphate, DCP) or by coating them with alveolar macrophage-specific
      ligands (maleylated bovine serum albumin, MBSA; and O-steroyl amylopectin, O
      SAP). The prepared formulations were characterized in vitro for vesicle
      morphology, mean vesicle size, and percent drug entrapment. Pressurized packed
      systems based on preformed liposomal formulations in chlorofluorocarbon aerosol
      propellants were prepared. In vitro airway penetration efficiency of the
      liposomal aerosols was determined by percent dose reaching the base of the lung,
      it was recorded 1.5-1.8 times higher as compared to plain drug solution-based
      aerosol. Percent viability of Mycobacterium smegmatis inside macrophages (in
      vitro) after administration of drug (in vivo) was in the range of 7-11% in the
      case of ligand-anchored liposomal aerosols, while it was recorded to be 45.7 and
      31.6% in case of plain drug and plain neutral liposomal aerosol (based on
      PC:Chol)-treated macrophages. Results suggest the preferential accumulation of
      MBSA- and O-SAP-coated formulations in the lung macrophages, which was further
      reflected in the periodically monitored in vivo tissue distribution studies.
      Higher lung drug concentration was recorded in case of ligand-anchored liposomal
      aerosols and negatively charged liposomal aerosols (based on PC:Chol:DCP) as
      compared to plain drug and plain liposome-based aerosols. The drug was estimated
      in the lung in high concentration even after 24h. The drug localization index
      calculated after 6h was nearly 1.4- and 3.5-fold, respectively, for both ligand
      appended liposome-based systems as compared to negatively charged and plain
      neutral liposome-based aerosolized systems. These results suggest that the ligand
      anchored liposomal aerosols are not only effective in rapid attainment of high
      drug concentration in lung with high population of alveolar macrophages but also
      maintain the same over prolonged period of time. The significance of targeting
      potential of the developed systems was established.

PMID- 14698576
TI  - Similarity approach to QSAR. Application to antimycobacterial benzoxazines.
AB  - The antimycobacterial activity in six series of substituted 3-phenyl-2H
      benzoxazine-2,4(3H)-dithiones and 3-(phenyl)-4-thioxo-2H-benzoxazine-2,4(3H)
      diones has been studied using a quantum molecular similarity approach. The
      approach is based on the use of fragment self-similarity measures as new
      universal molecular descriptors applicable for the design of novel theoretical
      QSAR models. Using this approach it was possible to show that while traditional
      QSAR models were able to describe the activity only within each of the six sets
      of studied molecules individually, the proposed approach is much more general and
      a single universal QSAR model describing the activity of all the 39 studied
      molecules in all the studied series together was built. The replacement of the
      oxo group by the thioxo group in position 4 on the benzoxazine ring of the
      antitubercular 3-(phenyl)-2H-benzoxazine-2,4(3H)-diones increases the activity,
      as well as the similar replacement in position 2.

PMID- 14698577
TI  - Stability and release characteristics of poly(D,L-lactide-co-glycolide)
      encapsulated CaPi-DNA coprecipitation.
AB  - The aims of this work were to determine the stability of DNA-calcium-phosphate
      coprecipitation (CaPi-DNA) against various conditions during double
      emulsification microencapsulation and assess the release and physicochemical
      characteristics of poly(D,L-lactide-co-glycolide) (PLGA) microparticles loading
      CaPi-DNA. CaPi-DNA prepared at pH 6.5 showed a good stability with over 60% CaPi
      DNA remained after emulsification, but no more than 40% at pH 8.0. Polyvinyl
      alcohol (PVA, 1-5%) could make over 80% CaPi-DNA (pH 7.0) preserved after
      homogenization. The dichloromethane (DCM), mixture of DCM and ethyl acetate,
      ether and n-hexane (1:1) exhibited neglectable influence on CaPi-DNA under
      homogenization. PLGA had influenced on CaPi-DNA without any additional
      stabilizer, in particular, PLGA (75:25, 4%, w/v) demonstrated a profound damage
      with only about 10% of the original CaPi-DNA remained. PLGA microparticles
      loading CaPi-DNA were spherical in shape with size range of 2.0-5.0microm, and
      entrapment efficiency 30-50%. CaPi-DNA was found to increase the stability of
      pDNA in PLGA microparticles without losing its structure integrity. The release
      of CaPi-DNA from microparticles showed a low burst release (<7.5%) within 24h and
      following sustained release process. The amount of cumulated CaPi-DNA release
      over 30 days was: 17.6% for PLGA (lactide:glycolide=50:50), 27.3% for PLGA
      (65:35) and 44.8% for PLGA (75:25) microparticles, respectively. The
      encapsulation of CaPi-DNA in microparticles could significantly protect CaPi-DNA
      from degradation of nuclease with average over 80% of total DNA recovery. These
      results suggested that the encapsulation of CaPi-DNA in PLGA microparticles could
      improve stability of pDNA.

PMID- 14698578
TI  - Effect of oligopeptides on gene expression: comparison of DNA/peptide and
      DNA/peptide/liposome complexes.
AB  - Plasmid DNA is known to form complexes with a variety of cationic peptides and
      lipids, which have been explored as possible carriers for DNA transfection in
      mammalian cells. We synthesized oligopeptides consisting of nine amino acid
      residues including lysine (K), tryptophan (W), and cysteine (C), and also their
      symmetrical dimmers with a disulfide bond as possible carriers. The
      pDNA(pGL3)/oligopeptide complexes generally showed poor transfection efficiencies
      but little cytotoxicity for HeLa S3. The ternary system of
      pDNA/oligopeptide/liposome containing cationic liposomes formulated from the
      cholesterol derivative (DMB-Chol) and dioleoylphosphatidylethanolamine (DOPE)
      showed 10(4)-10(5)-fold greater effective gene expression (10(8)-10(9) level,
      RLU/min/mg protein) than those of the corresponding pDNA/oligopeptide complexes.
      In the presence of 10% serum, the ternary complexes were maintained at 10(7)
      levels. The ethidium bromide exclusion studies showed the ternary complexes have
      much greater affinity to pDNA than the corresponding pDNA/oligopeptide complexes.
      Plasmid sensitivity against DNase I degradation showed that the ternary complexes
      were well protected from the digestion. Synthetic oligopeptides are active as
      potential enhancers for DOPE-containing cationic liposome-mediated transfection.
      These findings have implications for successful in vivo transfection.

PMID- 14698579
TI  - Determination of the changes in surface energetics of cefditoren pivoxil as a
      consequence of processing induced disorder and equilibration to different
      relative humidities.
AB  - The change in surface energy of cefditoren pivoxil powder as a consequence of
      changes in crystallinity (caused by milling duration) was studied using inverse
      gas chromatography (IGC) under dry conditions. The surface of the powder became
      more basic with decreasing crystallinity. It was suggested by considering the
      results of IR spectra that this resulted from exposure of the carbonyl groups,
      which have electron donating nature, on the particle surface. There was a direct
      correlation between surface energy and the % amorphous content induced during
      milling, giving the opportunity to use IGC to quantify amorphous content for this
      material. Furthermore, the changes in the acidic and basic properties on the
      surface of amorphous cefditoren pivoxil powder were investigated using IGC under
      various relative humidities (RHs). The basic nature on the surface of amorphous
      cefditoren pivoxil decreased with increasing RH, with a dramatic fall between 0
      and 10% RH, this was attributed to water preferentially shielding the exposed
      carbonyl groups from acidic polar probes. Since water molecules would be adsorbed
      to the most hydrophilic sites at initial RH increment, it seems reasonable to
      suppose that the most hydrophilic adsorption sites on the surface of amorphous
      cefditoren pivoxil are the exposed carbonyl groups.

PMID- 14698580
TI  - Synthesis and characterization of polyurethane and poly(ether urethane)
      nanocapsules using a new technique of interfacial polycondensation combined to
      spontaneous emulsification.
AB  - Polyurethane polymers and poly(ether urethane) copolymers were chosen as drug
      carriers for alpha-tocopherol. This active ingredient is widely used as a strong
      antioxidant in many medical and cosmetic applications, but is rapidly degraded,
      because of its light, heat and oxygen sensitivity. Polyurethane and poly(ether
      urethane)-based nanocapsules were synthesized by interfacial reaction between two
      monomers. Interfacial polycondensation combined with spontaneous emulsification
      is a new technique for nanoparticles formation. Nanocapsules were characterized
      by studying particle size (150-500 nm), pH, yield of encapsulation and
      morphologies. Polyurethanes (PUR) were obtained from the condensation of
      diisocyanate (isophorone diisocyanate: IPDI) and polyol: 1,2-ethanediol (EG), 1,4
      butanediol (BD), 1,6-hexanediol (HD). Poly(ether urethane) copolymers were
      obtained by replacing diols by polyethylene glycol oligomers (PEG) M(w) 200, 300,
      400 and 600. Molecular weights of di- and polyols have a considerable influence
      on nanocapsules characteristics cited above. The increase of molecular weight of
      polyols tends to increase the mean size of nanocapsules from (232+/-3)nm using EG
      to (615+/-39)nm using PEG 600, and led to the apparition of a population of
      agglomerate particles. We also noted that the yield of encapsulation increases
      with the increase of polyol length (from 85.6 to 92.2% w/w). Microscopic
      observations confirmed particle size analysis, but cannot predict the membrane
      structure owing the small size of the particles.

PMID- 14698581
TI  - Colonic drug delivery of 5-fluorouracil: an in vitro evaluation.
AB  - Compression coating has been found to be useful for colonic drug delivery. The
      aim of the present investigation was to design a formulation with a considerably
      reduced coat weight and gum concentration for colonic delivery of 5-fluorouracil
      for the treatment of colorectal cancer. Rapidly disintegrating core tablets
      containing 50 mg of 5-fluorouracil were prepared and compression coating with 175
      mg of granules containing a mixture of xanthan gum (XG) and guar gum (GG) in
      varying proportions was done. With this coat weight, a highly retarded drug
      release was observed. After 24h of dissolution the mean percent drug release from
      the compression coated XG:GG 20:20, 20:10 and 10:20 tablets were found to be
      around 18+/-1.23%, 20+/-1.54% and 30+/-1.77%, respectively. So, the coat weight
      was further reduced to 150 mg. It was observed that reduction of coat weight did
      not affect the initial drug release rate in simulated upper gastrointestinal
      tract (GIT) conditions. At the end of 24h of dissolution the amount of drug
      released increased to 25+/-1.22%, 36.6+/-1.89% and 42.6+/-2.22%, respectively in
      XG:GG 20:20, 20:10 and 10:20 tablets. Studies of XG:GG (10:20) tablets in
      presence of colonic contents showed an increased cumulative percent drug release
      of 67.2+/-5.23% in presence of 2% cecal content and 80.34+/-3.89% in presence of
      4% cecal content after 19 h of incubation.

PMID- 14698582
TI  - Transdermal iontophoresis of insulin: IV. Influence of chemical enhancers.
AB  - Transdermal iontophoresis per se may not be able to achieve significant
      permeation of large peptides like insulin, thereby necessitating the use of
      combination strategies involving chemical enhancers and iontophoresis. The study
      investigated effect of pre-treatment with commonly used vehicles such as ethanol
      (EtOH), propylene glycol (PG), water and their binary combinations, dimethyl
      acetamide (DMA), 10% dimethyl acetamide in water, ethyl acetate (EtAc) and
      isopropyl myristate (IPM) on insulin iontophoresis. Solvents, which acted on the
      lipid bilayer, were able to produce a synergistic enhancement with iontophoresis.
      The binary solvent systems produced either additive or no effect, when combined
      with iontophoresis. FT-IR studies showed that EtOH, DMA, EtAc caused lipid
      extraction and the former two also caused changes in skin proteins, whereas IPM
      caused increase in lipid fluidity. TGA studies showed that EtOH and PG caused
      dehydration of skin. Skin barrier property was severely compromised with DMA,
      followed by EtOH and EtAc, while IPM and PG had relatively minimum skin barrier
      altering potential. Thus, this study demonstrates the possibility of achieving
      higher permeation of large peptides like insulin by combining iontophoresis with
      chemical enhancers that act on the intercellular lipids.

PMID- 14698583
TI  - A mathematical approach to predicting the percutaneous absorption enhancing
      effect of sodium lauryl sulphate.
AB  - A study has been made of the effect of sodium lauryl sulphate (SLS) at several
      concentrations from 0.24 to 5% (w/w) on skin permeability. Seven model drugs were
      selected for this study on the basis of their lipophilicity as represented by
      their logP(oct) values (from -0.95 to 4.2). Skin pre-treatment with aqueous
      solutions of SLS does not increase the permeability coefficient of the most
      lipophilic compounds (logP(oct)> or =3). For the other compounds assayed the
      increase in the permeability coefficients depends on the concentration of SLS
      used in the skin pre-treatment, and on the lipophilicity of the compounds
      tested.The correlation between the inverse of SLS efficacy as an enhancer (1/ER)
      and the lipophilicity (logP(oct)) of the model permeants was established via a
      hyperbolic equation. This model makes it possible to predict the percutaneous
      absorption enhancing effect of SLS, expected for a compound of specific
      lipophilicity, according to the concentration used in skin pre-treatment. An
      excellent accuracy (r(2)>0.94) for the linear relationship between the
      experimental (n=15) and theoretical (ER) values predicted by the equation was
      obtained. The model proposed was also useful for experimental data obtained
      previously using Azone and compounds with the same range of lipophilicity.

PMID- 14698584
TI  - Preparation and in vitro evaluation of Eudragit microspheres containing
      acetazolamide.
AB  - The aim of this study was to prepare and evaluate Eudragit (RS and RL)
      microspheres containing acetazolamide. Microspheres were prepared by solvent
      evaporation method using acetone/liquid paraffin system. The influence of
      formulation factors (stirring speed, polymer:drug ratio, type of polymer, ratio
      of the combination of polymers) on particle size, encapsulation efficiency and in
      vitro release characteristics of the microspheres were investigated. The yields
      of preparation and the encapsulation efficiencies were high for all formulations
      the microspheres were obtained. Mean particle size changed by changing the
      polymer:drug ratio or the stirring speed of the system. Although acetazolamide
      release rates from Eudragit RS microspheres were very slow and incomplete for all
      formulations, they were fast from Eudragit RL microspheres. When Eudragit RS was
      added to Eudragit RL microsphere formulations, release rates slowed down and
      achieved the release profile suitable for peroral administration.

PMID- 14698585
TI  - Combined effect of SLS and (SBE)(7M)-beta-CD on the solubilization of NSC-639829.
AB  - Complexation and micellization are two effective ways of solubilizing drugs. In
      this study, the combined effect of surfactant and complexant on the
      solubilization of a poorly water soluble compound (NSC-639829) is investigated.
      With increasing concentration of sodium lauryl sulphate (SLS) in solutions of
      fixed concentration of (SBE)(7M)-beta-CD, the total solubility of the drug
      decreases linearly, reaches a minimum and then increases linearly. At each
      minimum, the molar ratio of SLS to (SBE)(7M)-beta-CD is close to unity. The above
      observation is attributed to the fact that the surfactant molecule competes with
      the drug to "fit" in the non-polar cyclodextrin cavity. The surfactant depletes
      cyclodextrin to form a 1:1 complex. Once the concentration of free SLS reaches
      the CMC, it starts forming micelles and hence, solubilizes the drug. A slight
      decrease of the solubilizing power is noticed in the presence of SLS/(SBE)(7M)
      beta-CD complex. The combined use of two solubilizing agents, a surfactant and a
      complexant, results in a much lower solubility than when either one is used alone
      at the same concentration. The surfactant molecule acts as a competitive
      inhibitor in the solubilization of the drug by the complexant. Similarly the
      complexant "pulls" the surfactant out of solution, making it unavailable for
      solubilizing the drug.

PMID- 14698586
TI  - The improvement of aqueous chemical stability of a model basic drug by ion
      pairing with acid groups of polyelectrolytes.
AB  - Carbomer (C) and procaine (P) were selected respectively as models of
      polyelectrolyte (PE) and basic drug (B) of low stability in aqueous solution. The
      purpose of this investigation was to test if a (C-P) aqueous system provides a
      microenvironment in which P is less exposed to hydroxyl ion catalyzed
      degradation, its main degradation pathway over a wide pH range. It was determined
      that in (C-P) a high fraction of P was present in the form of ion pairs [RCOO
      PH+] with the carboxylate groups of C. The [RCOO-PH+] fraction was above 97% for
      compositions containing higher than 50 mol% of P. The chemical stability of C-P
      was assayed at two selected pHs (7.5 and 8.5) in comparison with conventional
      reference solutions (RS) without C. Procaine in (C-P) was 4.2 and 6.2 times more
      stable than in its respective RS at the two conditions assayed. The stabilizing
      factor was calculated as the ratio of the rate constants k(obs)(RS)/k(obs)(C
      P).Since C-B systems exhibit negative electrokinetic potential that attracts
      positive ions such as (H+) and repels negative ones such as (OH(-)), the
      stabilizing effect would be associated with the higher acidity of (C-P)
      environment, in which PH+ molecules attached to the PE should also have lower
      kinetic energy than those in the bulk medium.

PMID- 14698587
TI  - Aqueous solubility study of salts of benzylamine derivatives and p-substituted
      benzoic acid derivatives using X-ray crystallographic analysis.
AB  - Twenty two p-substituted benzoic acid derivates were used to prepare salts of N
      methylbenzylamine (II) and N,N-dimethylbenzylamine (III), respectively. Only five
      salts of (II) and two salts of (III) were obtained in a crystalline state. The
      solubility of these salts was orders of magnitude higher than those reported for
      the corresponding salts of benzylamine (I). Thermal analysis indicated that the
      increased solubility was caused by reduced crystal lattice energy, which was most
      likely due to the reduced number of strong hydrogen bonds of the salt of (II) and
      (III). X-ray crystallographic analysis of p-hydroxybenzoic acid salt of (I), (II)
      and (III) suggested that the reduced number of hydrogen bonds caused the apparent
      higher solubility. Further analyses of seven salts of (I) were performed. It was
      not possible to identify any relationship between the number of hydrogen bonds
      and the corresponding solubility of the salts.

PMID- 14698588
TI  - Enhanced rectal bioavailability of ibuprofen in rats by poloxamer 188 and
      menthol.
AB  - To improve the bioavailability of poorly water-soluble ibuprofen in the rectum
      with poloxamer and menthol, the effects of menthol and poloxamer 188 on the
      aqueous solubility of ibuprofen were investigated. The dissolution and
      pharmacokinetic study of ibuprofen delivered by the poloxamer gels composed of
      poloxamer 188 and menthol were then performed. In the absence of poloxamer, the
      solubility of ibuprofen increased until the ratio of menthol to ibuprofen
      increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the
      ratio of 4:6, indicating that four parts menthol formed eutectic mixture with six
      parts ibuprofen. In the presence of poloxamer, the solutions with the same ratio
      of menthol to ibuprofen showed abrupt increase in the solubility of ibuprofen.
      The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15%
      poloxamer 188 showed the maximum solubility of ibuprofen, 1.2mg/ml. Menthol
      improved the dissolution rates of ibuprofen from poloxamer gels. Release
      mechanism showed that the release rate of ibuprofen from the poloxamer gels
      without menthol was independent of the time but the drug might be released from
      the poloxamer gels with menthol by Fickian diffusion. Furthermore, the poloxamer
      gel with menthol (poloxamer/menthol/ibuprofen (15%/0.25%/2.5%)) gave
      significantly higher initial plasma concentrations, C(max) and AUC of ibuprofen
      than did solid suppository, indicating that the drug from poloxamer gel could be
      more absorbed than that from solid one in rats. Thus, the poloxamer gel with
      poloxamer 188 and menthol was a more effective rectal dosage form for ibuprofen.

PMID- 14698589
TI  - The covalent coupling of HAV-VP3 (110-121) synthetic peptide to liposomes:
      physicochemical studies.
AB  - In this work we have studied the conjugation of the immunogenic peptide sequence
      (110-121) belonging to the VP3 capsid protein of hepatitis A virus to the surface
      of preformed liposomes by means of an amide bond between the vesicles and the
      synthetic peptide. The surface activity of the conjugate at air/water interface
      was determined. Moreover, the interaction of the conjugate with lipids was also
      studied recording the pressure increases produced after the injection of the
      liposome-peptide preparation under dipalmitoylphosphatidylcholine (DPPC),
      dipalmitoylphosphatidylglycerol (DPPG) and stearylamine (SA) monolayers at
      different initial surface pressures. As expected, due to the negative net charge
      of the liposome-peptide complex, the higher interaction was found with positive
      charge monolayers (SA). However, the conjugate was also able to incorporate to
      zwitterionic and anionic lipids. This behaviour was also confirmed performing
      compression isotherms of monolayers of these lipids spread on subphases
      containing the conjugate. These results suggest that the coupling of VP3 (110
      121) to liposomes does not influence its ability to interact with membrane lipids
      such as DPPC and DPPG. Then it can be assumed that its immunogenicity will be
      preserved or even increased after this modification. All these results are also
      useful in the preparation of liposome-based synthetic peptide vaccines.

PMID- 14698590
TI  - Dual-stimuli-responsive hydrogels based on poly(N-isopropylacrylamide)/chitosan
      semi-interpenetrating networks.
AB  - The synthesis and characterisation of semi-interpenetrating polymeric networks
      obtained by the radical-induced polymerisation of N-isopropylacrylamide in the
      presence of chitosan using tetraethyleneglycoldiacrylate as the crosslinker is
      described. The influence of the degree of crosslinking and that of the ratio of
      chitosan to poly(N-isopropylacrylamide) on the "pH/temperature induced" phase
      transition behaviour and swelling characteristics of the hydrogel system are
      investigated. The ability of the same system to act as a controlled release
      vehicle for pilocarpine hydrochloride is evaluated.

PMID- 14698591
TI  - Importance of using physiologically relevant volume of dissolution medium to
      correlate the oral exposure of formulations of BMS-480188 mesylate.
AB  - BMS-480188 is a weak base. The aqueous solubility of BMS-480188 is 0.036 mg/ml at
      pH 6.5 at 37 degrees C. The mesylate salt of BMS-480188 was prepared to improve
      its solubility. Capsules containing mesylate salt alone (Formulation A) or
      mesylate salt with excipients, including lactose, croscarmellose sodium, sodium
      lauryl sulfate, syloid and magnesium stearate (Formulation B), were prepared.
      Both formulations show similar dissolution profiles in 1l 0.01N HCl at 37 degrees
      C. However, the bioavailability of Formulations A and B is 5.7 and 24%,
      respectively, in monkeys. Since very small amount of fluid is available in the
      stomach of monkeys in fasted state, 30 ml of 0.01N HCl was used as the
      dissolution medium to simulate the ratio of the drug to dissolution medium in
      vivo. The dissolution studies in 30 ml of 0.01N HCl show that the amount of drug
      dissolved from the Formulation B is 80% greater than the Formulation A after 2h.
      These results are consistent with the higher bioavailability of the formulated
      capsules. The pK(a) of the free base is 3.0 and the apparent solubility of the
      mesylate salt (>20mg/ml) is much greater than the equilibrium solubility of BMS
      480188 (1.08 mg/ml) in 0.01N HCl at 37 degrees C. Therefore, the mesylate salt of
      BMS-480188 converts to the free base in 0.01N HCl. The presence of excipients
      delays the conversion of the mesylate salt to the free base in the dissolution
      test using 30 ml medium, leading to a greater percentage of the dissolved drugs.
      This inhibitory effect of excipients is masked during the dissolution using 1l
      medium because the concentration of the dissolved drug is below the solubility
      limit of BMS-480188. This study demonstrates the importance of the volume of the
      dissolution medium for the in vitro dissolution test to qualitatively predict the
      bioavailability of a salt of weak base with low intrinsic aqueous solubility.

PMID- 14698592
TI  - Is the use of a 200 ml vessel suitable for dissolution of low dose drug products?
AB  - This work evaluated the use of a commercially available 200 ml vessel for
      dissolution of five drug products with various solubilities. Each of the five
      drug products (four with USP monographs and one proprietary tablet formulation)
      was run at four different conditions (USP 25 monograph, six dosage units in
      single 1l vessel, 200 ml at the USP Monograph speed, and 200 ml at calculated
      paddle speed which matches the hydrodynamics of the USP vessel). Six dosage units
      in a single vessel were used as a comparison to increase the drug concentration
      for dissolution testing. Due to the different dissolution hydrodynamics, drug
      dissolution from the dosage forms was slower using the 200 ml conversion kit than
      when the USP method with a 1l vessel was used. However, use of the 200 ml vessel
      at higher paddle speeds calculated by the power/volume equation, yielded similar
      results as the monograph method. Thus, it appears that using the power/volume
      ratio calculation to obtain comparable hydrodynamics lends utility to the 200 ml
      vessel as a means for characterizing the dissolution profile of low dose solid
      oral drug products. The results of the multiple dosage units per vessel also gave
      similar results to that of the USP monograph method.

PMID- 14698593
TI  - The influence of transferrin stabilised magnetic nanoparticles on human dermal
      fibroblasts in culture.
AB  - Magnetic nanoparticles have been used for bio-medical purposes including drug
      delivery, cell destruction and as MRI contrast agents for several years. A more
      recent biological application has focused on targeted drug delivery. To this end,
      a wide variety of iron oxide nanoparticles have been synthesised. This study
      involves the use of magnetic nanoparticles synthesised and derivatised with human
      transferrin, compared to identical underivatised particles. Human fibroblasts
      were used, representative of a tissue cell-type. The influence in vitro was
      determined using light and fluorescence microscopy, scanning and transmission
      electron microscopy, and 1718 gene microarray. The results indicate that the
      transferrin derivatised particles appear to localise to the cell membrane without
      instigating receptor-mediated endocytosis, and also induce up-regulation in the
      cells for many genes, particularly in the area of cytoskeleton and cell
      signalling. The microscopy results further support these findings.

PMID- 14698594
TI  - Formation and characterization of three-component-sorbitan monoester surfactant,
      oil and water-creams.
AB  - The effect of molecular structure of four sorbitan monoester surfactants
      (sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate and sorbitan
      monooleate) on the formation of simple three-component creams is presented.
      Interfacial properties of the surfactants were determined using a du Nouy
      tensiometer and rheological properties of selected creams with oscillation stress
      sweep, creep recovery and viscosity tests. Depending on the composition, sorbitan
      monolaurate and sorbitan monooleate formed both o/w creams and w/o creams, while
      sorbitan monopalmitate and sorbitan monostearate formed only o/w creams. Sorbitan
      monostearate and sorbitan monopalmitate had the smallest cmc and A(cmc) values
      and they were the most effective surfactants in lowering the interfacial tension.
      These surfactants formed the most stable and elastic creams with clear linear
      viscoelastic regions and small compliance values. Sorbitan monolaurate and
      sorbitan monooleate formed viscous creams without elastic properties.

PMID- 14698595
TI  - Integrated oral bioavailability projection using in vitro screening data as a
      selection tool in drug discovery.
AB  - The objective of the analysis described herein is to examine the in vitro/in vivo
      relationship of estimated bioavailability values and also the applicability of
      the estimated in vitro bioavailability to lead candidate selection in drug
      discovery. To this end, in vitro ADME data from screening assays as well as in
      vivo rat pharmacokinetic (PK) data were compiled for 140 compounds across
      therapeutic areas from the Pfizer library in Ann Arbor. The compounds span a
      broad range of structural types, including neutral, basic, and acidic compounds.
      Solubility and Caco-2 permeability data from in vitro ADME screening were used to
      calculate the fraction dose absorbed (FDp) using the physiologically based IDEA
      model. In vitro metabolic stability (t(1/2)) from human and rat liver microsomal
      incubations was converted to an in vitro intrinsic clearance value (CL(int)'),
      which was then scaled up to reflect in vivo clearance (CL) and hepatic extraction
      as described by Obach et al. [J. Pharmcol. Exp. Ther. 283 (1997) 46].
      Subsequently, the in vitro/in vivo relationship between the measured
      bioavailability (F(obs)) in rats and the estimated bioavailability (F(est)) from
      FDp and predicted CL values was examined. The observed data suggest that
      compounds with low estimated in vitro bioavailability (F(est)<15%) are more
      likely to have low in vivo bioavailability (F(obs)<30%). Therefore, the present
      study indicates that in vitro estimation of bioavailability is an efficient tool
      to eliminate compounds having low bioavailability prior to in vivo
      characterization and therefore can be used to reduce attrition due to poor ADME
      properties in drug development.

PMID- 14698596
TI  - Bioavailability enhancement of a poorly water-soluble drug by solid dispersion in
      polyethylene glycol-polysorbate 80 mixture.
AB  - Oral bioavailability of a poorly water-soluble drug was greatly enhanced by using
      its solid dispersion in a surface-active carrier. The weakly basic drug (pK(a)
      approximately 5.5) had the highest solubility of 0.1mg/ml at pH 1.5, < 1
      microg/ml aqueous solubility between pH 3.5 and 5.5 at 24+/-1 degrees C, and no
      detectable solubility (< 0.02 microg/ml) at pH greater than 5.5. Two solid
      dispersion formulations of the drug, one in Gelucire 44/14 and another one in a
      mixture of polyethylene glycol 3350 (PEG 3350) with polysorbate 80, were prepared
      by dissolving the drug in the molten carrier (65 degrees C) and filling the melt
      in hard gelatin capsules. From the two solid dispersion formulations, the PEG
      3350-polysorbate 80 was selected for further development. The oral
      bioavailability of this formulation in dogs was compared with that of a capsule
      containing micronized drug blended with lactose and microcrystalline cellulose
      and a liquid solution in a mixture of PEG 400, polysorbate 80 and water. For
      intravenous administration, a solution in a mixture of propylene glycol,
      polysorbate 80 and water was used. Absolute oral bioavailability values from the
      capsule containing micronized drug, the capsule containing solid dispersion and
      the oral liquid were 1.7+/-1.0%, 35.8+/-5.2% and 59.6+/-21.4%, respectively.
      Thus, the solid dispersion provided a 21-fold increase in bioavailability of the
      drug as compared to the capsule containing micronized drug. A capsule formulation
      containing 25 mg of drug with a total fill weight of 600 mg was subsequently
      selected for further development. The selected solid dispersion formulation was
      physically and chemically stable under accelerated storage conditions for at
      least 6 months. It is hypothesized that polysorbate 80 ensures complete release
      of drug in a metastable finely dispersed state having a large surface area, which
      facilitates further solubilization by bile acids in the GI tract and the
      absorption into the enterocytes. Thus, the bioavailability of this poorly water
      soluble drug was greatly enhanced by formulation as a solid dispersion in a
      surface-active carrier.

PMID- 14698597
TI  - Immobilisation of GM-CSF onto particulate vaccine carrier systems.
AB  - Physical connection of vaccine carriers with immunostimulating cytokines may
      provide an interesting possibility to enhance the immune response of protective
      or therapeutic vaccines. As a first evaluation, various aluminium hydroxide
      adjuvants and poly(D,L-lactide-co-glycolide) (PLGA) microparticulates with
      modified positively and negatively charged surfaces were prepared to adsorb
      granulocyte-macrophage colony-stimulating factor (GM-CSF) under different pH
      conditions. Negatively charged surfaces were chosen to resemble physiological
      binding of GM-CSF to extracellular glycosaminoglycans, while modified positively
      charged surfaces may enhance GM-CSF adsorption due to electrostatic interaction.
      Release of GM-CSF was checked in vitro in a simulated interstitial environment.
      Anionic and cationic surfaces efficiently attracted GM-CSF to the carrier surface
      independently of the pH, while the composition of the carrier largely influenced
      the release of GM-CSF over time. Thus, the adsorption of GM-CSF to aluminium
      hydroxide adjuvants and PLGA microparticulates provides a simple and efficient
      possibility to physically connect the cytokine with these commonly used and
      potential vaccine carriers and may enable its localised delivery to the side of
      action.

PMID- 14698598
TI  - Feasibility of preparing nanodrugs by high-gravity reactive precipitation.
AB  - To study the feasibility of producing nanoparticles of organic pharmaceuticals
      using a novel high-gravity reactive precipitation (HGRP) technique, reactive
      precipitation of benzoic acid as a model compound was carried out in a rotating
      packed bed under high gravity. The main factors such as the rotating bed speed,
      concentration and volume flow rate of the reactants (sodium benzoate and HCl)
      affecting the particle size of the precipitate were studied. Particle size was
      measured by transmission electron microscopy. Benzoic acid was precipitated as
      nanoparticles as fine as 10nm. The particle size was decreased with increasing
      rotating bed speed, concentration and volume flow rate of the reactants. The
      formation of ultrafine particles was due to intensified micro-mixing of reactants
      in the rotating bed to enhance nucleation while suppressing crystal growth. The
      results have demonstrated the feasibility to produce nanodrugs by the principle
      of acid-base precipitating reaction using HGRP.

PMID- 14698599
TI  - Living with the enemy: a physiological role for the beta-amyloid peptide.

PMID- 14698600
TI  - Deconstructing the axon: Wallerian degeneration and the ubiquitin-proteasome
      system.

PMID- 14698601
TI  - NMDA receptor subunit gating--uncovered.

PMID- 14698603
TI  - Coding and learning of behavioral sequences.

PMID- 14698605
TI  - Spines and dendrites cannot be assumed to distribute dye evenly.

PMID- 14698606
TI  - Excitotoxic and oxidative cross-talk between motor neurons and glia in ALS
      pathogenesis.

PMID- 14698607
TI  - Synaptic frailty and clathrin-mediated synaptic vesicle trafficking in
      Alzheimer's disease.

PMID- 14698608
TI  - Interneuron Diversity series: Fast in, fast out--temporal and spatial signal
      processing in hippocampal interneurons.

PMID- 14698609
TI  - Functional organization of PLC signaling microdomains in neurons.

PMID- 14698610
TI  - GPCR-mediated transactivation of RTKs in the CNS: mechanisms and consequences.

PMID- 14698611
TI  - Olfactory ensheathing cells and CNS repair: going solo or in need of a friend?

PMID- 14698612
TI  - The origins and implications of Aluternative splicing.
AB  - Ten percent of the human genome is composed of highly repetitive DNA sequences
      called Alu elements. It has recently been found that at least 5% of all human
      alternative exons are derived from Alu elements. Moreover, single nucleotide
      mutations can convert either alternative or otherwise silent Alu elements into
      constitutive exons and this can lead to the development of human disease. These
      results provide new insights into the function and dangers of 'junk DNA' in the
      human genome.

PMID- 14698613
TI  - The ins and outs of transcriptional control: nucleocytoplasmic shuttling in
      development and disease.
AB  - Recent findings relating to SOX transcription factors indicate that defects in
      organogenesis can be caused not only by impairment of the biochemical properties
      of transcription factors but also, in some cases, by deficient nuclear import. In
      addition, experimentally interfering with the nuclear export signals of some SOX
      factors has now been found to cause developmental defects. Controlling the
      balance of nuclear import and export might be a common means by which
      transcription factor activity can be regulated during development, and defects in
      these processes might underlie a broader spectrum of inherited developmental
      disorders.

PMID- 14698614
TI  - L1 (LINE-1) retrotransposon diversity differs dramatically between mammals and
      fish.
AB  - L1 retrotransposons replicate (amplify) by copying (reverse transcribing) their
      RNA transcript into genomic DNA. The evolutionary history of L1 in mammals has
      been unique. In mice and humans approximately 80 million years of L1 evolution
      and replication produced a single evolutionary lineage of L1 elements while
      generating approximately 20% of the genomic mass in each species. By contrast,
      zebrafish contain >30 distinct L1 lineages that have generated approximately one
      tenth as much DNA. We contend that, by becoming far more permissive of
      interspersed repeated DNA than other organisms, mammals are conducive to
      competition between L1 families for replicative dominance, and that this
      competition, perhaps for the host factors required for L1 replication, results in
      a single L1 lineage.

PMID- 14698615
TI  - Anything else but GAGA: a nonhistone protein complex reshapes chromatin
      structure.
AB  - The packaging of DNA in the cell nucleus is a major obstacle, but also a crucial
      means of control in processes such as DNA replication, recombination and gene
      transcription. Studies in recent years have revealed that dynamic changes in the
      basic nucleosome structure of chromatin play a key role, particularly in the
      activation and silencing of gene expression. It is widely assumed that these
      changes are often linked to equally important, but as yet poorly understood,
      modifications of higher-order chromatin architecture. Recent studies in the fruit
      fly Drosophila melanogaster show how protein complexes that bind to 'GAGA' DNA
      elements can replace nucleosomes to create a local chromatin environment that
      facilitates a variety of site-specific regulatory responses. In this article, I
      will summarize recent insights into the composition and architecture of GAGA
      binding protein complexes, and discuss their multifaceted role in homeotic gene
      regulation.

PMID- 14698616
TI  - Acquiring signalling specificity from the cytokine receptor gp130.
AB  - Repeated use of a relatively small number of intracellular signalling molecules
      specifies tissue- and cell-type-specific responses to pleiotropic-acting growth
      factors and cytokines. Currently, gaining a better understanding of these
      mechanisms is a major challenge. The IL-6 family of cytokines shares a common
      receptor subunit called gp130. Phenotypic comparisons of mice with amino acid
      knock-in substitutions that disable individual signalling modules in gp130, with
      knockout mice lacking ligand-specific gp130 activation or transgenic mice with
      constitutive gp130 activation, has led to the identification of two molecular
      mechanisms. One mechanism is based on differential target-gene responsiveness to
      signalling threshold levels transduced by either the STAT1/3 or the SHP2/ERK
      cascade, which are under reciprocal negative regulation and together account for
      the majority of intracellular gp130 signalling. The second mechanism is based on
      the capacity of certain cell types to integrate the often-conflicting information
      transduced by these two pathways, and to prevent pathological responses.

PMID- 14698617
TI  - Collagens, modifying enzymes and their mutations in humans, flies and worms.
AB  - Collagens and proteins with collagen-like domains form large superfamilies in
      various species, and the numbers of known family members are increasing
      constantly. Vertebrates have at least 27 collagen types with 42 distinct
      polypeptide chains, >20 additional proteins with collagen-like domains and
      approximately 20 isoenzymes of various collagen-modifying enzymes. Caenorhabditis
      elegans has approximately 175 cuticle collagen polypeptides and two basement
      membrane collagens. Drosophila melanogaster has far fewer collagens than many
      other species but has approximately 20 polypeptides similar to the catalytic
      subunits of prolyl 4-hydroxylase, the key enzyme of collagen synthesis. More than
      1300 mutations have so far been characterized in 23 of the 42 human collagen
      genes in various diseases, and many mouse models and C. elegans mutants are also
      available to analyse the collagen gene family and their modifying enzymes.

PMID- 14698618
TI  - Riboswitches: the oldest mechanism for the regulation of gene expression?
AB  - Riboswitches are structures that form in mRNA and regulate gene expression in
      bacteria. Unlike other known RNA regulatory structures, they are directly bound
      by small ligands. The mechanism by which gene expression is regulated involves
      the formation of alternative structures that, in the repressing conformation,
      cause premature termination of transcription or inhibition of translation
      initiation. Riboswitches regulate several metabolic pathways including the
      biosynthesis of vitamins (e.g. riboflavin, thiamin and cobalamin) and the
      metabolism of methionine, lysine and purines. Candidate riboswitches have also
      been observed in archaea and eukaryotes. The taxonomic diversity of genomes
      containing riboswitches and the diversity of molecular mechanisms of regulation,
      in addition to the fact that direct interaction of riboswitches with their
      effectors does not require additional factors, suggest that riboswitches
      represent one of the oldest regulatory systems.

PMID- 14698619
TI  - Alanine tracts: the expanding story of human illness and trinucleotide repeats.
AB  - Expansions of polyglutamine repeats are known to cause a variety of human
      neurodegenerative diseases. More recently, expansions of alanine tracts,
      particularly in transcription factor genes, have been shown to cause at least
      nine human conditions, including mental retardation and malformations of the
      brain, digits and other structures. Present knowledge suggests that alanine tract
      expansions generally, but not always, arise through unequal recombination as
      opposed to replication slippage, the most likely mechanism in other triplet
      repeat expansions. The function of alanine tracts is unknown but when alanine
      expansions occur in transcription factor genes, alanine tracts can result in
      either loss-of-function or gain of an abnormal function. Given the frequency of
      alanine tracts in proteins, it is likely that more alanine tract expansions will
      be discovered in disease genes.

PMID- 14698620
TI  - Serpin identification, production, and characterization.

PMID- 14698621
TI  - Computational analysis of evolution and conservation in a protein superfamily.
AB  - Many gene superfamilies have hundreds or thousands of members and hence pose a
      significant challenge when performing a large-scale phylogenetic analysis.
      Derivation of the most accurate alignment possible and inference of evolutionary
      relationships (with an appropriate measure of confidence) are significant
      "bottlenecks" in the process. A generally applicable strategy is outlined for
      identifying and aligning sequences, performing simple analysis of the resulting
      alignment, and inferring evolutionary relationships. Reference is made to the
      serpin superfamily. The 'partition cluster' method, a relatively rapid technique
      for extracting underlying associations from phylogenetic bootstrap trees, is also
      presented.

PMID- 14698622
TI  - Serpin-ligand interactions.
AB  - One of the more common features of serpins is the ability to bind various
      ligands. Ligand binding can occur so that the inhibitory properties of the serpin
      are regulated, so that the serpin can be localized, or to produce or modulate
      some other biological function of the serpin. Ligands known to affect serpin
      biologic activity include glycosaminoglycans such as heparin, heparan sulfate and
      dermatan sulfate, DNA, extracellular matrix proteins such as vitronectin and
      collagen, and small organic molecule hormones. Many different biochemical and
      biophysical techniques in conjunction with molecular biology and cell biology
      approaches have been used to study the binding of various ligands to serpins and
      to assess the influence of this binding on activity and structure. We summarize
      here the different approaches that have been used to identify serpin ligands and
      the many methods that have been used to characterize the interactions of these
      ligands with their cognate serpins.

PMID- 14698623
TI  - Use of fluorescence resonance energy transfer to study serpin-proteinase
      interactions.
AB  - One of the important questions in the serpin mechanism of inhibition of serine
      and cysteine proteinases of different specificities and structural classes is
      whether a common "crushing" mechanism of proteinase inactivation is used in all
      cases. This mechanism was seen in an X-ray structure of the complex between
      alpha(1)-proteinase inhibitor and trypsin and required the full insertion of the
      reactive center loop into beta-sheet A and translocation of the proteinase from
      one pole of the serpin to the other. However, it has yet to be shown to be
      general for serine proteinases of structural classes other than the trypsin-fold
      or for cysteine proteinases with the papain-fold or for the caspases.
      Fluorescence resonance energy transfer offers a potential means of obtaining an
      answer to this question for each of these classes, without the concern for the
      effect that increasing size has on the observed signal that applies to NMR
      spectroscopy. However, care must be taken to ensure that measurements made
      represent sufficient overdetermination that the answer obtained is unambiguous.

PMID- 14698624
TI  - Use of NMR to study serpin function.
AB  - Two-dimensional heteronuclear [1H,15N] single quantum correlation NMR spectra of
      serpins show dramatic changes between native and loop-inserted conformations,
      making them very sensitive reporters of the serpin conformation. Much of the
      spectral overlap that arises when all amides are 15N labelled can be removed by
      use of selective labelling of a single type of amino acid, such as alanine. The
      method allows ready determination of whether loop insertion is present, and to
      what extent, as well as providing information on motional freedom of components
      of the complex and of the reactive center loop. With label introduced separately
      into the proteinase, information can also be obtained on the conformational
      changes brought about in that moiety by complex formation. In addition, with the
      use of cryoprobes, high field spectrometers, TROSY-based signal detection and
      deuteration, samples as small as 1-2mg can easily be examined, making it
      applicable to a wide range of serpins, including those that can only be expressed
      in mammalian cells.

PMID- 14698625
TI  - Serpin mutagenesis.
AB  - Mutagenesis represents a powerful methodology for the analysis of protein
      structural and functional relationships and dissection of complex protein-protein
      interactions. The suicide substrate-like inhibitory mechanism of the proteins of
      the serpin superfamily offers unique challenges for the design of mutagenesis
      studies. All serpins share a well-characterized core structure and most adopt a
      metastable conformation that is required for inhibitory activity. Mutagenesis
      studies focused on the reactive center loop, the hinge region, protease-binding
      exo-sites, conformational stability, and accessory ligand binding domains have
      led to a well-established serpin inhibitory mechanism and have defined specific
      biological interactions and functions for a number of serpins in development,
      homeostasis, and host defense. Nonetheless, great care must be taken in the
      design and interpretation of serpin mutagenesis studies, since the rapid
      conformational changes that occur during serpin inhibition can be affected at
      many levels.

PMID- 14698626
TI  - Production, characterization, and use of serpin antibodies.
AB  - Serine protease inhibitors (serpins) constitute a still expanding superfamily of
      structural similar proteins, which are localized extracellularly and
      intracellularly. Serpins play a central role in the regulation of a wide variety
      of (patho) physiological processes including coagulation, fibrinolysis,
      inflammation, development, tumor invasion, and apoptosis. Serpins have a unique
      mechanism of inhibition that involves a profound change in conformational state
      upon interaction with their protease. This conformational change enables the
      production of monoclonal antibodies specific for native, complexed, and
      inactivated serpins. Antibodies, and assays based on these antibodies, have been
      helpful in elucidating the (patho) physiological function of serpins in the last
      decade. Serpin-specific antibodies can be used for: (1) structure-function
      studies such as detection of conformational changes; (2) identification of target
      proteases; (3) the detection and quantification of serpin and serpin-protease
      complexes in bodily fluids by immunoassays such as ELISA, RIA or FACS; (4)
      detection of serpins in tissues by immunohistochemistry; and (5) possible
      therapeutical interventions. This review summarizes the techniques we have used
      to obtain and screen antibodies against extra- and intracellular serpins, as well
      as the use of these antibodies for some of the above-mentioned purposes.

PMID- 14698627
TI  - Physical characterization of serpin conformations.
AB  - The native serpin fold is characterized by being metastable. This thermodynamic
      characteristic is manifested in the conversion of the native state to other more
      stable conformations. Whilst this structural transition is required for
      proteinase inhibition and regulation of a range of biological phenomena,
      inappropriate structural changes can result in a number of disease states.
      Identification of these alternative conformations has been essential in our
      understanding of serpin structure and function. However, identifying these
      alternative forms is also important if we are not to misinterpret data due to the
      formation of these states during in vitro studies. The different physical
      properties of these alternative serpin conformational states make it possible to
      use a range of standard laboratory techniques to identify these structures. In
      this chapter, we will outline these general approaches that can be used routinely
      to identify the alternative serpin conformational states.

PMID- 14698628
TI  - Measurement of the kinetic parameters mediating protease-serpin inhibition.
AB  - Serine protease inhibition by proteins of the serpin family is a unique and
      complex process involving physical, chemical, and conformational changes. After
      encounter with the reactive site of inhibitor, the protease is conformationally
      trapped as a covalent complex resembling the acyl-protease intermediate of
      catalysis. The stability of the trap is not permanent and may vary for different
      proteases. In addition, the trapping mechanism is not 100% efficient and a
      fraction of the serpin may be consumed like a substrate before inactivation is
      complete. Characterization of protease-serpin inhibition therefore requires the
      measurement of three parameters: the apparent second order rate constant of
      inhibition (k(inh)), the stoichiometry of inhibition (SI), and the rate of
      complex breakdown (k(brkdn)). The basic kinetic methods to establish these
      parameters are described.

PMID- 14698629
TI  - Production of recombinant serpins in Escherichia coli.
AB  - Expression systems based on Escherichia coli offer fast, cheap, and convenient
      means for the production of recombinant serpins. Over 30 active serpins from
      prokaryotic and eukaryotic organisms have been produced in this way, using a
      variety of vectors, promoters, fusion partners, and host strains. Serpins forming
      insoluble inclusion bodies in E. coli can generally be solubilized and refolded.
      Here, we outline the general approaches and procedures to be considered when
      contemplating the use of E. coli for recombinant serpin production.

PMID- 14698630
TI  - Production of serpins using baculovirus expression systems.
AB  - Headpin is a novel serine proteinase inhibitor (serpin) that is downregulated in
      many established HNSCC tumor cell lines and human oral SCC specimens. The use of
      the bacterial and yeast expression systems for headpin resulted in poor yields
      and proteins with low inhibitory activity. To circumvent these problems, we have
      developed a baculovirus-insect cell system for high-yield expression as well as
      fully functional protein. Here, we describe the strategies and methods used to
      express headpin in an insect cell heterologous system. In addition, procedures to
      purify the recombinant proteins are described. A metal affinity column followed
      by a gel-filtration chromatography provides a rapid and efficient method for
      large quantity preparation of headpin. This method should be useful as an
      alternative expression system for those serpins that are not purifiable when
      expressed using the Escherichia coli or yeast expression system.

PMID- 14698631
TI  - Production of serpins using yeast expression systems.
AB  - Serpins occupy a unique niche in the field of biology. As more of them are
      discovered, the need to produce sufficient quantities of each to aid experimental
      and therapeutic research increases. Yeast expression systems are well suited for
      the production of recombinant serpins. The genetics of many yeast species is well
      understood and readily manipulated to induce the targeted over-production of many
      different serpins. In addition, protease-deficient strains of certain species are
      available and a few species carry out post-translational modifications resembling
      those of humans. Yeasts are easy to grow and multiply readily in simple culture
      media hence the cost of production is low, while the scale of production can be
      small or large. The disadvantages are the inability of most yeast(s) to perform
      complex post-translational modifications and a lower product yield of secreted
      protein compared to intracellular protein production. However, for the
      intracellular production of serpins, in particular the clade B serpins that do
      not have complex post-translational modifications, yeast expression systems
      should be among the first systems considered.

PMID- 14698632
TI  - Serpin production using rapid in vitro transcription/translation systems.
AB  - In vitro transcription/translation systems are becoming more useful to produce
      proteins and determine the protein function. Expression of proteins in vitro
      provides a rapid and controllable system to express proteins. The ability to
      control the system by addition of other compounds has allowed for the production
      of proteins that had been difficult to produce by conventional expression
      systems. More recently, the development of continuous in vitro systems has
      allowed the production of larger quantities of proteins for downstream
      purification techniques. Also, the use of different cell lysates allows for
      specific post-translational modifications of the synthesized proteins. The
      ability to label the translated proteins can aid structural analysis and allow
      tracking of specific proteins.

PMID- 14698634
TI  - The role of bone in osteoarthritis. Proceedings of the 2001 Coral Gables
      Symposium.

PMID- 14698633
TI  - Production and activation of recombinant papain-like cysteine proteases.
AB  - Papain-like cysteine proteases are the most numerous family of the cysteine
      protease class. They are expressed throughout the animal and plant kingdoms as
      well as in viruses and bacteria. More recently, this protease family has drawn
      attention as a potential pharmaceutical drug target in diseases characterized by
      excessive extracellular matrix degradation such as in osteoporosis, arthritis,
      vascular diseases, and cancer. Moreover, papain-like cysteine proteases have been
      identified as critical components of the life cycle and invasive potential of
      various human and live stock pathogens as well as major allergens. Therefore,
      this protease class is rigorously studied and requires sufficient amounts of
      protease protein to analyze structure-activity relationships, their 3-D
      structures as well as to screen for and optimize potent and selective inhibitors.
      This review summarizes approaches to generate active papain-like cysteine
      proteases by heterologous expression in a variety of expression systems.

PMID- 14698635
TI  - The role of joint architecture in the etiology of arthritis.
AB  - Focal degenerative changes occur in some joints very early in life. These changes
      in the articular cartilage appear to occur in the unloaded, rather than the
      loaded, areas of the joint. One possible cause for this pattern of degeneration
      is lack of use or stress in these particular areas of the joint; just as unused
      bone and unused muscle atrophy, so may unused cartilage. If these unloaded areas
      were never subjected to mechanical stress, degeneration at these sites perhaps
      would not be important. However, bones, including their articular ends, are in a
      constant state of change through the process of remodeling, which continues
      throughout life. Joint surfaces are not, in general, spherical, and therefore
      must be incongruent during most of their arc of movement. In the young person,
      this incongruity maintains physiologic loading and joint nutrition. Studies have
      shown age-related changes in the remodeling process that lead to increasing joint
      congruity in old age. These age-related increases in congruity may result in a
      redistribution of load in the joint such that there is an increased stress on
      formerly unloaded atrophic cartilage. Arthritis always results in a change in
      joint shape. It is suggested that a change in shape caused by a disturbance in
      the remodeling process may itself be an important contributing cause of
      osteoarthritis.

PMID- 14698636
TI  - Subchondral bone changes in hand and knee osteoarthritis detected by radiography.
AB  - OBJECTIVE: To describe the changes in subchondral bone that occur with the onset
      and progression of osteoarthritis (OA) from macroradiographic assessment of
      patient's hand and knee joints. DESIGN: The high magnification and spatial
      resolution of macroradiography permits detailed anatomical changes to be detected
      in OA joints. Data on the subchondral cortical and cancellous bone, recorded from
      both cross-sectional and longitudinal studies of hand and knee OA, are described
      and discussed with reference to recent findings on the altered biomechanical
      properties of OA bone. RESULTS: In OA joints, both subchondral cortical plate and
      subjacent horizontal trabeculae increase in thickness early, prior to joint space
      narrowing (JSN). With progression, cortical plate sclerosis increased in 60% of
      OA hands and did not change in knee OA until JSN <1.5mm in the medial diseased
      compartment. In knee OA, trabeculae, at sites of tibial subchondral sclerosis,
      increased in number and extent, changes that overlay a subarticular region that
      was osteoporotic. With cartilage loss, the articular surfaces in some knees
      appeared corrugated, and later, with bone-on-bone, the surfaces became flattened
      and deformed. CONCLUSIONS: The weaker than normal bone within thickened
      subchondral cortical plate and trabeculae of OA joints leads, in advanced OA, to
      deformation of the articular surfaces and absorption of local stresses producing
      an effect similar to stress-shielding. This effect, it is suggested, results in
      the subarticular osteoporosis.

PMID- 14698637
TI  - Anatomy and physiology of the mineralized tissues: role in the pathogenesis of
      osteoarthrosis.
AB  - Synovial joints are composed of several different kinds of tissue that interact
      to protect normal joint function. Three subchondral mineralized tissues can be
      identified-calcified cartilage, subchondral cortical bone, and subchondral
      trabecular bone-which are distinguished morphologically, physiologically, and
      mechanically. Each responds to mechanical and pharmaceutical stimuli in different
      ways through processes of growth, modeling, and remodeling, and changes in each
      may have a distinct effect on the health of the joint. It is important to
      distinguish between the structural properties of these tissues and their material
      properties as these change differently in osteoarthrosis (OA). It is likely that
      changes in the mineral content and thickness of the calcified cartilage play a
      greater role in the pathogenesis of OA than has been realized, whereas changes in
      trabecular bone are probably not causative. Changes in the subchondral cortical
      bone may accelerate progression of pre-existing disease, but the combined effects
      of increased subchondral bone turnover and greater subchondral bone volume are
      not at all clear. Ultimately, the efficacy of bone anti-resorptive therapies for
      OA will depend upon whether the increased structural stiffness of the subchondral
      mineralized tissues predisposes the cartilage to deteriorate, whether the
      increased bone turnover that occurs in OA is itself a causative factor, or
      whether the lower tissue elastic modulus offsets the increased structural
      stiffness of the subchondral plate in an attempt to protect the cartilage from
      damage.

PMID- 14698638
TI  - Pathophysiology of osteoarthritis.

PMID- 14698639
TI  - The role of bone in the treatment of osteoarthritis.
AB  - Bone, and especially the subchondral bone plate, is involved in the pathogenesis
      of osteoarthritis (OA). OA bone tissue is sclerotic yet undermineralized
      indicating abnormal bone cell metabolism. Studies in both human and animal models
      of OA support the concept that bone sclerosis could precede cartilage degradation
      and loss. Clinical studies show that the indices of bone resorption and formation
      are increased in OA patients. A working hypothesis of the sequence of changes
      leading to OA holds that enhanced bone remodeling is the initiating event
      triggering cartilage damage. The attempt to repair the damaged cartilage then
      leads to a number of biochemical adaptations in bone and cartilage. In bone, this
      repair attempt modifies insulin-like growth factor 1 (IGF-1), IGF binding
      proteins (IGFBPs), and transforming growth factor-beta (TGF-beta), and alters the
      urokinase plasminogen activator (uPA)/plasmin system. In the cartilage, it also
      modifies IGF-1/IGFBP levels and the uPA/plasmin system. However, bone changes may
      overwhelm the attempts to repair cartilage, and lead to further sclerosis and
      damage. Some of these specific pathways have been investigated, and indeed are
      modified in OA subchondral osteoblasts. Thus, subchondral bone sclerosis in OA
      may be due to abnormal osteoblasts characterized by increased metabolic
      activities that result in an increase in osteoid matrix that is undermineralized.
      The exact role played by cytokines and prostaglandins remains controversial.
      However, restraining collagen deposition and mineral removal, and/or improving
      mineral deposition, could provide a better, more mineralized, bone matrix in OA
      patients.

PMID- 14698640
TI  - Risk factors for osteoarthritis: genetics.
AB  - Although the multifactorial nature of osteoarthritis (OA) is well recognized,
      genetic factors have been found to be strong determinants of the disease.
      Evidence of a genetic influence of OA comes from a number of sources, including
      epidemiological studies of family history and family clustering, twin studies,
      and exploration of rare genetic disorders. Classic twin studies have shown that
      the influence of genetic factors is between 39% and 65% in radiographic OA of the
      hand and knee in women, about 60% in OA of the hip, and about 70% in OA of the
      spine. Taken together, these estimates suggest a heritability of OA of 50% or
      more, indicating that half the variation in susceptibility to disease in the
      population is explained by genetic factors. Studies have implicated linkages to
      OA on chromosomes 2q, 9q, 11q, and 16p, among others. Genes implicated in
      association studies include VDR, AGC1, IGF-1, ER alpha, TGF beta, CRTM (cartilage
      matrix protein), CRTL (cartilage link protein), and collagen II, IX, and XI.
      Genes may operate differently in the two sexes, at different body sites, and on
      different disease features within body sites. OA is a complex disease, and
      understanding its complexity should help us find the genes and new pathways and
      drug targets.

PMID- 14698641
TI  - Bone mineral density and osteoarthritis: data from the Baltimore Longitudinal
      Study of Aging.
AB  - BACKGROUND: Numerous cross-sectional studies have shown that persons with
      radiographic features of osteoarthritis (OA) of the hips and knees have higher
      adjusted levels of bone mineral density (BMD). OBJECTIVE: Data from the Baltimore
      Longitudinal Study of Aging were examined to determine (1) whether persons with
      radiographic features of OA of the hands and knees had different rates of bone
      loss than subjects with normal knee radiographs, and (2) whether persons with
      normal knee radiographs who had higher adjusted levels of BMD were at greater
      risk of developing radiographic features of knee OA. DESIGN: Longitudinal cohort
      study. SUBJECTS: 298 Caucasian men and 139 Caucasian women aged 20 and above who
      had radiographs of the hands and knees read for features of OA and two or more
      measurements of BMD at the forearm at least 4 years apart. 179 Caucasian men and
      110 Caucasian women aged 20 and above who had longitudinal knee radiographs on
      average 10 years apart, a subgroup of whom had baseline measurement of lumbar
      spine and/or femoral neck BMD. RESULTS: Women with radiographic OA of the hand
      had a significantly greater adjusted rate of bone loss at the radius than women
      with normal hand radiographs; no such differences were noted in men for hand OA.
      There were no significant differences in adjusted rate of bone loss at the radius
      in men or women by presence of radiographic knee OA. Higher BMD at the lumbar
      spine but not at the femoral neck was associated with an increased risk of
      developing incident radiographic knee OA after adjustment for age, gender, and
      body mass index. CONCLUSIONS: These data demonstrate that persons with
      radiographic OA lose bone at different rates than those with normal radiographs
      and that this relationship varies between the site of OA and the site of
      measurement of BMD. In addition, they further support a role for higher bone mass
      in the development of radiographic knee OA. Further studies are needed to examine
      the relationship between changes in bone mass and radiographic progression of OA.

PMID- 14698642
TI  - Can we identify a 'high risk' patient profile to determine who will experience
      rapid progression of osteoarthritis?
AB  - Disease modifying drugs for osteoarthritis (OA) that may halt or retard joint
      destruction and at the same time possibly improve symptoms are being developed
      and tested at various stages in clinical trials. This has, for at least two
      reasons, focused attention on the need for identification of patient groups at
      high risk for incident or progressive OA. First, well characterized such groups
      may be useful in clinical trials. Second, assuming that disease modifying OA
      drugs become available in the future, primary target groups in need of such
      therapy have to be identified. Risk factors for incident OA may differ from those
      for OA progression. Interactions between risk factors for OA is little
      understood. Factors that have consistently been reported as associated with
      radiographic OA progression are obesity, generalized OA, alignment and synovitis.
      Other factors such as bone scintigraphic lesions, joint injury nad biomarkers
      (such as type II collagen fragments, COMP and HA) show promise. Further
      evaluation of these variables and their individual and combined influence will be
      useful to design a risk profile for OA incidence and progression.

PMID- 14698643
TI  - Are osteophytes good or bad?

PMID- 14698644
TI  - Monitoring osteoarthritis progression and therapy.
AB  - Monitoring the progression of osteoarthritis (OA) and the effects of therapy
      during clinical trials requires valid and reliable outcome measurements. This
      paper discusses the selection of outcome measures in Phase III clinical trials of
      OA, the importance of presenting these variables in terms of the response of
      individual patients, and the combination of information from several outcome
      measures into a composite index. Four domains-pain, physical function, patient
      global assessment, and joint imaging (for studies >;1 year in duration)-have been
      identified as core outcome measures for Phase III clinical trials of OA. Within
      the symptom severity domains, several measurement instruments may be considered,
      including visual analog scales (VAS), the Western Ontario McMasters Universities
      Osteoarthritis (WOMAC) Index, the Lequesne Functional Severity Index, and the
      Arthritis Impact Measurement Scales (AIMS). Imaging techniques consist of
      radiography, magnetic resonance imaging (MRI), or other techniques. Although
      evaluation of these variables is often based on the average improvement in the
      study population as a whole, evaluation in terms of individual patients is more
      relevant. Therefore, continuous data collected from individuals (e.g., pain VAS 0
      100mm) require conversion to a dichotomous variable (e.g., improvement yes/no) so
      that the percentage of responders can be determined. Continuous data from
      individual patients' data may be converted to a dichotomous variable based on
      global assessments, statistical modeling, or predictive capacities. Such methods
      suggest that a change in joint space width of >/=0.5mm may be considered
      clinically relevant. A composite index combining symptomatic and structural
      efficacy variables, adverse events, costs, and the requirement for surgery into a
      single variable would be useful. The requirement for total hip arthroplasty has
      been evaluated as a composite outcome measure for trials of hip OA and found to
      be valid, simple, and clinically pertinent.

PMID- 14698645
TI  - How do we best measure the clinical benefit of a structure-modifying
      osteoarthritis drug?

PMID- 14698646
TI  - Rationale for the use of structure-modifying drugs and agents in the treatment of
      osteoarthritis.
AB  - This paper summarizes our current stand on potential pathophysiological targets
      for osteoarthritis (OA) therapies. Although OA is a complicated disease,
      involving the cartilage, synovial membrane, and subchondral bone, a number of
      interactive pathways have been found to explain the structural changes in the
      disease process. Study of these three tissues has yielded a list of targets to
      examine for their potential to affect disease progression. At the cartilage
      level, therapeutic agents, such as growth factors, could be targeted to increase
      chondrocyte anabolism. At the synovial level, cytokines and cytokine receptor
      antagonists are potential targets for therapy. In the subchondral bone,
      cytokines, growth factors and eicosanoids, and locally synthesized factors
      affecting bone metabolism are also potential targets of therapy. Recent progress
      in the understanding of the pathophysiology of OA has led to exploration of
      several interesting new approaches toward the treatment of this disease. New
      classes of molecules that inhibit one or more OA disease processes are under
      evaluation for their potential to alter the degenerative process. The prospect of
      finding a cure for OA is more promising than ever. Based on the discovery of
      major pathophysiological pathways leading to the structural changes observed in
      OA, novel ways to treat the progression of OA lesions are emerging.

PMID- 14698647
TI  - Measurement of structure (disease) modification in osteoarthritis.
AB  - Osteoarthritis (OA) research is beginning to focus on developing structure
      (disease) modifying treatments that will stabilize or reverse morphological
      changes, thereby altering the underlying pathologic process. The ability of anti
      arthritic agents to modify the course of disease has been investigated in a
      limited number of clinical trials. Agents studied in published clinical trials
      include glycosaminoglycan-peptide complex (GP-C), glycosaminoglycan polysulfate
      (GAGPS), diacerein, and glucosamine sulphate. These clinical trials have been
      difficult to interpret and compare because the patients studied are often
      inadequately characterized or are not comparable across studies. Studies also
      vary with respect to the outcome measures analyzed and the methodology applied to
      measurement and data analysis. Further, in general, the rate of radiographic
      progression of OA is slow and is not consistent across populations and patients
      with varying disease severity. In man, the radiograph has been the gold standard
      for evaluating treatments. Further longitudinal validation of the radiograph is
      needed. As techniques improve, variation in the system and the number of patients
      needed in studies are decreasing. It may be that the radiograph will not achieve
      the needed degree of validation and will be supplanted by magnetic resonance
      imaging as the surrogate marker of joint status.

PMID- 14698648
TI  - Thrombosis in children with acute lymphoblastic leukemia Part III. Pathogenesis
      of thrombosis in children with acute lymphoblastic leukemia: effects of host
      environment.
AB  - This concluding section of the series will evaluate the role of host environment
      in the development of thromboembolism (TE) in children with acute lymphoblastic
      leukemia (ALL). The available evidence suggests that TE in association with
      childhood ALL is a multifactorial entity resulting from the interaction of the
      disease, chemotherapy and its effects, and possible prothrombotic states inherent
      to the host. The few studies conducted so far in children with ALL have reported
      wide variability in the prevalence of prothrombotic defects and its impact on the
      risk of TE. The prevalence of prothrombotic defects varies in different ethnic
      population. Since different ALL therapy studies use different chemotherapeutic
      agents in various dosage and combination, it is important that every major study
      group assesses the risk of TE, including the prevalence of prothrombotic defects,
      within their therapy plan. This will help to identify the population at risk for
      TE and for thromboprophylaxis, if indicated.

PMID- 14698649
TI  - Bedside monitoring of coagulation activation after challenging healthy volunteers
      with intravenous endotoxin.
AB  - INTRODUCTION: In the intensive care, many patients are at risk of developing
      procoagulant changes leading to severe coagulopathy and disseminated
      intravascular coagulation (DIC). Close monitoring of the coagulation is therefore
      crucial. In this study, we assess a novel bedside instrument based on free
      oscillating rheometry, measuring the degree of coagulation activity as clotting
      onset time, COT. COT measurements are conducted in whole blood, and thus reflect
      the overall hemostasis. MATERIALS AND METHODS: Nine healthy volunteers were
      subjected to intravenous injection of 2 ng/kg endotoxin. To quantify the
      activation of the coagulation system, COT was assessed along with prothrombin
      fragment 1 + 2 (F1 + 2) and activated partial thromboplastin time (aPTT).
      RESULTS: Baseline COT was 10.6 +/- 3.6 min. Three hours after endotoxin
      injection, maximal body temperature and heart rate were registered. At this time,
      an activation of the coagulation was observed as a significant decrease in COT to
      8.0 +/- 1.0 min, a decrease in aPTT and increased levels of F1 + 2. COT levels,
      body temperature and heart rate subsequently normalized towards initial levels.
      F1 + 2 however continued to increase throughout the study. CONCLUSIONS: COT is a
      rapid test, performed in less than 15 min. COT was superior to F1+ 2 in
      monitoring the endotoxin-induced activation of the coagulation, since COT
      covariated with clinical symptoms, whereas F1 + 2 did not. This is, to our
      knowledge, the first time an overall coagulation monitoring method has been
      assessed bedside to detect endotoxin-induced activation of the coagulation. The
      COT test shows promising results, but further studies are needed to reveal its
      potential in the intensive care monitoring arsenal.

PMID- 14698650
TI  - Signs of thrombin generation in pediatric cardiac catheterization with
      unfractionated heparin bolus or subcutaneous low molecular weight heparin for
      antithrombotic cover.
AB  - INTRODUCTION: Thrombosis is one of the most frequent adverse events after cardiac
      catheterization, which can be reduced by anticoagulation with unfractionated
      heparin (UFH) in both children and adults. Low molecular weight heparin (LMWH)
      might possibly offer advantages. Laboratory signs of thrombin generation during
      pediatric cardiac catheterization, with unfractionated heparin (UFH) bolus or
      subcutaneous LMWH for thrombosis prophylaxis, were determined in a first step to
      investigate the potential of LMWH for antithrombotic cover. MATERIALS AND
      METHODS: Signs of thrombin generation (D-dimer and F1+2), anti-Xa activity and
      activated clotting time (ACT) were measured in 65 patients with congenital heart
      disease. A total of 40 patients were treated with a UFH bolus of 100 IU/kg
      bodyweight and, in 25 children, enoxaparin was subcutaneously administered at a
      dosage of 1/1.6 mg/kg bodyweight. RESULTS: The dose to plasma activity of
      enoxaparin was more consistent than in the UFH group. Only a slight elevation of
      F1+2 was found in some patients, which was a little higher in the enoxaparin
      group, but no difference of incidence of increased F1+2 generation was detected
      between the two groups. D-dimer was elevated in three children after UFH bolus
      application, but no such effect was observed in any child after LMWH
      administration. CONCLUSIONS: Application of LMWH was equally efficacious during
      pediatric cardiac catheterization than UFH bolus administration, as determined by
      plasma levels and markers of clotting activation. In contrast to UFH bolus, no
      further monitoring was necessary after the application of LMWH during cardiac
      catheterization due to a consistent dose to plasma activity.

PMID- 14698651
TI  - Preserved endothelial vasomotion and fibrinolytic function in patients with acute
      stent thrombosis or in-stent restenosis.
AB  - INTRODUCTION: Acute stent thrombosis and in-stent restenosis are serious
      complications of percutaneous coronary intervention (PCI) and may be associated
      with vascular or platelet abnormalities. We aimed to assess endothelium-dependent
      vasomotion, endogenous fibrinolysis and platelet function in patients with acute
      stent thrombosis or in-stent restenosis. MATERIALS AND METHODS: Thirty-six
      subjects were enrolled into four groups: acute stent thrombosis, in-stent
      restenosis, uncomplicated PCI with stent implantation and healthy matched
      controls. Forearm blood flow was measured using bilateral venous occlusion
      plethysmography during intra-brachial acetylcholine, substance P and sodium
      nitroprusside infusion. Venous blood samples were withdrawn for estimation of
      plasma fibrinolytic variables and platelet aggregometry. RESULTS: Acetylcholine,
      substance P and sodium nitroprusside caused dose-dependent increases in blood
      flow (P < 0.001) and substance P caused a dose-dependent increase in tissue-type
      plasminogen activator (t-PA) release (P < 0.001) in all groups. Thrombin,
      collagen, adenosine diphosphate (ADP) and the thromboxane A2 analogue, U46619,
      caused dose-dependent platelet aggregation (P < 0.001) in all groups. There were
      no significant between group differences in these responses except that, in
      keeping with aspirin therapy, collagen-induced platelet aggregation was impaired
      in patient groups compared with healthy controls (P < 0.01). Post-hoc analysis
      demonstrated a significant impairment of acute t-PA release in current smokers
      compared to non-smokers (P < 0.05). CONCLUSIONS: Despite previous reports
      suggesting impaired vascular function, endothelium-dependent vasomotion,
      endogenous fibrinolysis and platelet aggregation do not appear to play a major
      role in the pathogenesis of acute stent thrombosis or in-stent restenosis.

PMID- 14698652
TI  - Prevalence of hyperhomocysteinemia and the MTHFR C677T polymorphism in patients
      with arterial and venous thrombosis from North Western Russia.
AB  - Conflicting data from Western European and USA population studies led us to
      investigate hyperhomocysteinemia (HHcy), the methylenetetrahydrofolate reductase
      (MTHFR) C677T polymorphisms and thrombotic disease in North Western Russia.
      Plasma total homocysteine (tHcy) levels, MTHFR C677T genotype, selected life
      style determinants and haemostatic factor activity were determined in patients
      with arterial (n = 33), venous (n = 40), arterial + venous (n = 11) thrombosis
      and healthy controls (n = 30). We found raised median tHcy levels in all patient
      groups vs. controls (p < 0.05), with odds ratios (95% CI) for vascular disease
      among patients with HHcy (defined as > 15 micromol/l) of 3.9 (0.6 - 14.3), 4.8
      (1.2 - 18.8) and 15.8 (2.8 - 87.3) respectively. tHcy levels were a function of
      MTHFR C677T genotype, and all patients with tHcy levels > 30 micromol/l had the
      MTHFR C677T homozygous substitution. Elevated tHcy levels (p < 0.05) were
      identified in smokers and coffee drinkers, with the degree of elevation dependent
      on MTHFR C677T genotype. Of the studied haemostatic parameters increased factor
      VIII activity and vWF antigen and activity was observed in HHcy subjects. We
      conclude that HHcy and MTHFR C677T genotype are positively associated with
      arterial and venous thrombotic disease in the population of North Western Russia.

PMID- 14698653
TI  - Possible contribution of acetylamrinone and its enhancing effects on platelet
      aggregation under shear stress conditions in the onset of thrombocytopenia in
      patients treated with amrinone.
AB  - BACKGROUND: Thrombocytopenia is recognized as one of the most common
      complications when the patients with severe heart failure are treated with
      cardiotropic phosphodiesterase (PDE)-3 inhibitors. To understand the mechanism of
      the onset of this complication, we focused on the effects of various PDE-3
      inhibitors and its stable metabolite of acetylamrinone on platelet aggregation
      occurring under physiological shear stress conditions. METHOD: Blood specimens
      were obtained from eight apparently healthy adult donors. Platelet-rich plasma
      was separated after anticoagulation by citrate. The effects of PDE-3 inhibitors
      of amrinone and olprinone, as well as the stable metabolite of the former of
      acetylamrinone, on platelet aggregation induced by its exposure to a shear rate
      of 1200 and 10,800 s(-1) were determined by optically modified cone-plate
      viscometer. RESULTS: Both olprinone and amrinone inhibited platelet aggregation
      at 10,800 s(-1) in a dose-dependent manner with the IC(50) value of 14 +/- 1 and
      61 +/- 8 microM (mean +/- S.D.), respectively, while amrinone significantly
      inhibited platelet aggregation at 1200 s(-1) only at highest concentration tested
      (100 microM). Contrary to the effects shown with PDE-3 inhibitors, acetylamrinone
      did not inhibit platelet aggregation at all. Moreover, it even enhanced the
      aggregation at 1200 s(-1) when used with 5 microM. CONCLUSIONS: Our results
      demonstrate possible contribution of the enhancing effects of acetylamrinone on
      platelet aggregation occurring under blood flow conditions, which reduced the
      platelet count when occurring in real circulation, to the higher incidence of
      thrombocytopenia in patients treated with amrinone.

PMID- 14698654
TI  - Effect of sodium selenite treatment on platelet aggregation of streptozotocin
      induced diabetic rats.
AB  - INTRODUCTION: There is a well-known association between diabetes and
      atherosclerosis. Platelets are involved in the development of atherosclerotic
      vascular diseases and play a key role in atherosclerotic complications. Diabetes
      mellitus is related to alteration in the homeostasis of selenium and the
      protective role of selenium against lipid peroxidation in diabetes is reported.
      In the present study, thrombin-induced platelet aggregation and thromboxane A2
      (TxA2) formation in diabetes and the effect of sodium selenite were evaluated.
      MATERIALS AND METHODS: Diabetes was induced by intraperitoneal injection of
      streptozotocin (STZ) in Wistar rats (n = 21). Thirty of them were used as control
      rats. A week after streptozotocin injection, 11 of the control rats and 12 of the
      diabetics were injected with 5 micromol/kg/day of sodium selenite for 4 weeks.
      Thrombin-induced aggregation of the platelets was evaluated by optical technique.
      Thromboxane B2 (TxB2), TxA2 metabolite, was measured by enzyme-linked immunoassay
      (EIA) in thrombin-induced platelets. RESULTS AND CONCLUSION: The platelet
      aggregation and TxB2 level increased in diabetic rats. Sodium selenite reversed
      the increase in platelet aggregation and TxB2 and caused a small but significant
      (p < 0.05) decrease in the glucose level. The hyperaggregability of platelets in
      STZ-induced diabetic rats was thought to be related to the enhanced TxA2
      formation of platelets. Increase in TxA2 formation implies lipid peroxidation.
      Sodium selenite decreased the TxA2 formation. Besides its antioxidative effect,
      further studies are needed to establish the insulin-like effect of selenite
      because of a small decrease in blood glucose.

PMID- 14698655
TI  - Soluble tissue factor as predictor of future events in patients with acute
      myocardial infarction.

PMID- 14698656
TI  - Template-directed dye-terminator incorporation with fluorescence polarization
      detection for analysis of single nucleotide polymorphisms associated with
      cardiovascular and thromboembolic disease.

PMID- 14698657
TI  - Lipopolysaccharide attenuates thrombolysis in batroxobin-induced lung vasculature
      fibrin deposition but not in ferrous chloride-induced carotid artery thrombus in
      rats: role of endogenous PAI-1.
AB  - In this study, we investigated if elevation of endogenous plasminogen activator
      inhibitor type 1 (PAI-1) by lipopolysaccharide (LPS) can retard thrombolysis in
      both a rat model of lung vasculature fibrin deposition and a platelet-rich
      thrombus model induced by endothelial injury. By 3 h following an intravenous
      bolus injection of 0.5 mg/kg LPS, the plasma PAI-1 level had increased to
      approximately 8 ng/ml. 125I-labeled fibrinogen was injected intravenously
      followed by an injection of batroxobin. Batroxobin converts fibrinogen into
      insoluble fibrin, which was then deposited in the lungs within 5 min, followed by
      spontaneous fibrinolysis that completely cleared fibrin deposition in the lungs
      by 30 min. In rats pre-treated with LPS, spontaneous fibrinolysis was
      significantly retarded. In the endothelial injury model, topical application of
      FeCl2 on the carotid artery induced an occlusive platelet-rich thrombus, which
      was not sensitive to endogenous thrombolysis. Exogenous tissue-type plasminogen
      activator (tPA) was required to recanalize the occlusive thrombus in a dose
      dependent manner. Pre-treatment with LPS did not alter the dose-response curve of
      exogenous tPA-induced thrombolysis. These data indicate that batroxobin-induced
      lung vasculature fibrin deposition in rats, unlike the FeCl2 model, is sensitive
      to the impact of endogenous PAI-1 on fibrinolysis.

PMID- 14698658
TI  - Evidence for genetic susceptibility to thrombosis in idiopathic intracranial
      hypertension.

PMID- 14698659
TI  - New insights into the evolutionary relationships between arenaviruses provided by
      comparative analysis of small and large segment sequences.
AB  - Arenaviruses are rodent-borne negative-stranded bisegmented RNA viruses. Five
      arenaviruses are etiologic agents of hemorrhagic fever in humans and are
      potential agents of bioterrorism. They are classified as Biosafety level 4 agents
      and listed in the category A of the Pathogen Agents edited by the Center for
      Disease Control and Prevention. To date, evolution and phylogeny of arenaviruses
      have been based on the analysis of sequences derived from structural genes (small
      RNA segment) exclusively, due to the lack of sequences available for the large
      RNA segment. In this study, partial sequences of the polymerase gene were
      determined for 18 species of arenaviruses and used to investigate phylogenetic
      relationships. Comparative analysis of topologies obtained from polymerase and
      structural gene analyses permitted us to determine the evolutionary origin of the
      major parent of the North American recombinant arenaviruses, and to investigate
      the role of genetic exchange (reassortment and recombination) in the evolutionary
      mechanisms driving the evolution of the genus Arenavirus.

PMID- 14698660
TI  - Quasispecies variation of porcine reproductive and respiratory syndrome virus
      during natural infection.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) displays notorious
      genetic, antigenic, and clinical variability. Little is known, however, about the
      nature and extent of viral variation present within naturally infected animals.
      By amplifying and cloning the open reading frame 5 gene from tonsils of naturally
      infected swine, and by sequencing individual clones, we characterized viral
      diversity in nine animals from two farms. All animals harbored multiple PRRSV
      variants at both the nucleic and the amino acid levels. Structural variation and
      rates of synonymous and nonsynonymous nucleotide substitution were no different
      within known epitopes than elsewhere. Analysis of molecular variance indicated
      that differences between farms, among animals within farms, and within individual
      animals accounted for 92.94, 3.84, and 3.22% of the total viral genetic
      variability observed, respectively. PRRSV exists during natural infection as a
      quasispecies distribution of related genotypes. Positive natural selection for
      immune evasiveness does not appear to maintain this diversity.

PMID- 14698661
TI  - Identification of amino acids essential for the human parainfluenza type 2 virus
      V protein to lower the intracellular levels of the STAT2.
AB  - The V protein of SV41 targets STAT1, while a specific loss of STAT2 is induced by
      the hPIV2 V protein. We established HeLa cells constitutively expressing various
      chimeric proteins between the hPIV2 and SV41 V proteins, and which STAT (STAT1 or
      2) was expressed in these cells was analyzed. Both the P-V common domain and the
      V specific domain of hPIV2 V protein are necessary for STAT2 lowering. The
      internal domain (aa145-173) containing a large number of nonidentical amino acids
      between hPIV2 and SV41 does not direct STAT tropism, and the regions necessary
      for STAT2 lowering are discontinuous. The N-terminal domain (aa1-104) and the
      internal domain (aa126-196) of the hPIV2 V protein do not determine STAT tropism.
      HeLa cells expressing A105E or H108P show distinct expression of STAT2, but do
      show low expression or a loss of STAT1, indicating that the amino acid residues
      105 and 108 of the hPIV2 V protein are essential for STAT2 lowering.
      Interestingly, there is an important amino acid(s) in the region (aa121-125) for
      STAT2 lowering, and the presence of either amino acid residue 123 or 125 of the
      hPIV2 V protein is necessary for lowering of STAT2. In addition, HeLa cells
      expressing S216D or 1217R expressed STAT2, but no STAT1, indicating that the
      amino acid residues 216 and 217 of the hPIV2 V protein are indispensable for
      STAT2 lowering. HeLa/hPIV2V cells and HeLa/S104/P are resistant to IFN-beta,
      while they are sensitive to IFN-gamma. On the other hand, HeLa/SV41V, HeLa/S216D,
      and HeLa1217R cells are resistant to both IFNs. Intriguingly, HeLa/A105E and
      HeLa/H108P cells were found to be sensitive to IFN-gamma.

PMID- 14698662
TI  - The genome of the Cryptophlebia leucotreta granulovirus.
AB  - The genome of the Cryptophlebia leucotreta granulovirus (CrleGV) was sequenced
      and analyzed. The double-stranded circular genome contains 110907 bp and
      potentially encodes 129 predicted open reading frames (ORFs), 124 of which were
      similar to other baculovirus ORFs. Five ORFs were CrleGV specific and 26 ORFs
      were common to other granulovirus genomes. One ORF showed a significant
      similarity to a nonstructural protein of Bombyx mori densovirus-2. A baculovirus
      chitinase gene was identified, which is most likely not functional, because its
      central coding region including the conserved chitinase active site signature is
      deleted. Three gene copies (Crle20, 23, and 24) containing the Baculo PEP N
      domain of the polyhedron envelope protein were identified in CrleGV and other GV
      genomes. One of them (Crle23) appeared also to contain a p10-like sequence
      encoding of a number of leucine-rich heptad repeats and a proline-rich domain.
      Another striking feature of the genome is the presence of a hypervariable non-hr
      ori-like region of about 1800 bp consisting of different kinds of repeats and
      palindromes. Three other repeat-rich regions were identified within the genome
      and are considered as homologous regions (hrs). CrleGV is most closely related to
      the Cydia pomonella granulovirus (CpGV) as revealed by genome order comparisons
      and phylogenetic analyses. However, the AT content of the CrleGV genome, which is
      67.6% and the highest found so far in baculoviruses, differed by 12.8% from the
      AT content of CpGV. This resulted in a major difference in the codon usage of
      both viruses and may reflect adaptive selection constraints to their particular
      hosts.

PMID- 14698664
TI  - Identification and molecular characterization of a naturally occurring RNA virus
      mutant defective in the initiation of host recovery.
AB  - The host recovery response is characterized by the disappearance of disease
      symptoms and activation of the RNA silencing virus resistance in the new growth
      following an initial symptomatic infection. However, it is not clear what
      triggers the initiation of recovery, which occurs naturally only in some virus
      host interactions. Here we report the identification and characterization of a
      spontaneous mutant of Tobacco streak virus (TSV) that became defective in
      triggering recovery in tobacco plants. Infectious full-length cDNA clones
      corresponding to the tripartite RNA genome were constructed from both the wild
      type and the nonrecovery mutant of TSV (TSVnr), the first sets of infectious cDNA
      clones from an Ilarvirus. Genetic and molecular analyses identified an A --> G
      mutation in the TSVnr genome that was sufficient to confer nonrecovery when
      introduced into TSV. The mutation was located in the intergenic region of RNA 3
      upstream of the mapped transcriptional start site of the coat protein mRNA.
      Intriguingly, induction of recovery by TSV was not accompanied by virus clearance
      and TSV consistently accumulated to significantly higher levels than TSVnr did
      even though TSVnr-infected plants displayed severe symptoms throughout the course
      of infection. Thus, our findings indicate that recovery of host can be initiated
      by minimal genetic changes in a viral genome and may occur in the absence of
      virus clearance. Mechanisms possibly involved in the initiation of host recovery
      are discussed.

PMID- 14698663
TI  - Overexpression of gK in gK-transformed cells collapses the Golgi apparatus into
      the endoplasmic reticulum inhibiting virion egress, glycoprotein transport, and
      virus-induced cell fusion.
AB  - Intracellular transport and egress of alphaherpesviruses require the coordinate
      function of multiple proteins and glycoproteins. Recently, we showed that gK is
      expressed on infected cell surfaces and that gK cell-surface expression required
      the presence of the UL20 protein [J. Virol. 77 (2003), 499]. Overexpression of gK
      by gK-transformed cells blocked transport of enveloped virions from perinuclear
      spaces and inhibited virus-induced cell fusion caused by gK syncytial mutants [J.
      Virol. 69 (1995), 5401]. Therefore, we investigated whether altered synthesis and
      transport of gK was responsible for the observed gK-mediated interference
      phenomena. HSV-1 infection of the gK-transformed cell line Vero (gK9) caused a
      profound entrapment of gK in the endoplasmic reticulum and total inhibition of gK
      cell surface expression. In addition, gK drastically inhibited intracellular
      transport and maturation of gD and caused substantial defects in Golgi-dependent
      glycosylation of gB. Visualization of intracellular organelles via confocal
      microscopy revealed a profound collapse of the Golgi apparatus into the
      endoplasmic reticulum. These results were analogous to those observed in the
      presence of brefeldin A, a known Golgi disruptor. Therefore, virion entrapment
      within perinuclear spaces and inhibition of glycoprotein transport are due to gK
      mediated collapse of the Golgi apparatus.

PMID- 14698665
TI  - The double-stranded RNA-activated protein kinase mediates viral-induced
      encephalitis.
AB  - The double-stranded (ds) RNA-activated protein kinase (PKR) plays an important
      role in control of viral infections and cell growth. We have studied the role of
      PKR in viral infection in mice that are defective in the PKR signaling pathway.
      Transgenic mice were derived that constitutively express a trans-dominant
      negative kinase-defective mutant PKR under control of the beta-actin promoter.
      The trans-dominant-negative PKR mutant expressing transgenic mice do not have a
      detectable phenotype, similar to observations with PKR knock-out mice. The
      requirement for PKR in viral pathogenesis was studied by intracerebral infection
      of mice with a mouse-adapted poliovirus. Histopathological analysis revealed
      diffuse encephalomyelitis with severe inflammatory lesions throughout the central
      nervous system (CNS) in infected wild-type mice. In contrast, histopathological
      evaluation of virus-injected trans-dominant-negative PKR transgenic mice as well
      as PKR knock-out mice yielded no signs of tissue damage associated with
      inflammatory host responses. However, the virus did replicate in both models of
      PKR-deficient mice at a level equal to that observed in wild-type infected mice.
      Although the results indicate a clear difference in susceptibility to poliovirus
      induced encephalitis, this difference manifests clinically as a slight delay in
      fatal neuropathy in trans-dominant-negative PKR transgenic and PKR knock-out
      animals. Our observations support the finding that viral-induced PKR activation
      may play a significant role in pathogenesis by mediating the host response to
      viral CNS infection. They support PKR to be an effective target to control tissue
      damage due to deleterious host responses to viral infection.

PMID- 14698666
TI  - Translation efficiency determines differences in cellular infection among dengue
      virus type 2 strains.
AB  - We have investigated the molecular basis for differences in the ability of
      natural variants of dengue virus type 2 (DEN2) to replicate in primary human
      cells. The rates of virus binding, virus entry, input strand translation, and RNA
      stability of low-passage Thai and Nicaraguan and prototype DEN2 strains were
      compared. All strains exhibited equivalent binding, entry, and uncoating, and
      displayed comparable stability of positive strand viral RNA over time in primary
      cells. However, the low-passage Nicaraguan isolates were much less efficient in
      their ability to translate viral proteins. Sequence analysis of the full-length
      low-passage Nicaraguan and Thai viral genomes identified specific differences in
      the 3' untranslated region (3'UTR). Substitution of the different sequences into
      chimeric RNA reporter constructs demonstrated that the changes in the 3'UTR
      directly affected the efficiency of viral translation. Thus, differences in
      infectivity among closely related DEN2 strains correlate with efficiency of
      translation of input viral RNA.

PMID- 14698667
TI  - A duck hepatitis B virus strain with a knockout mutation in the putative X ORF
      shows similar infectivity and in vivo growth characteristics to wild-type virus.
AB  - Hepadnaviruses including human hepatitis B virus (HBV) and duck hepatitis B virus
      (DHBV) express X proteins, HBx and DHBx, respectively. Both HBx and DHBx are
      transcriptional activators and modulate cellular signaling in in vitro assays. To
      test whether the DHBx protein plays a role in virus infection, we compared the in
      vivo infectivity and growth characteristics of a DHBV3 strain with a stop codon
      in the X-like ORF (DHBV3-X-K.O.) to those of the wild-type DHBV3 strain. Here we
      report that the two strains showed no significant difference in (i). their
      ability to induce infection that resulted in stable viraemia measured by serum
      surface antigen (DHBsAg) and DHBV DNA, and detection of viral proteins and
      replicative DNA intermediates in the liver; (ii). the rate of spread of infection
      in liver and extrahepatic sites after low-dose virus inoculation; and (iii). the
      ability to produce transient or persistent infection under balanced age/dose
      conditions designed to detect small differences between the strains. Thus, none
      of the infection parameters assayed were detectably affected by the X-ORF
      knockout mutation, raising the question whether DHBx expression plays a
      physiological role during in vivo infection with wild-type DHBV.

PMID- 14698668
TI  - Species-specific transformation of T cells by HV(MNE).
AB  - HV(MNE) is an Epstein-Barr virus (EBV)-like lymphocryptovirus (LCV) originally
      isolated from a Macaca nemestrina with CD8(+) T cell mycosis fungoides/cutaneous
      T cell lymphoma (Blood 98 (2001), 2193). HV(MNE) transforms rabbit T cells in
      vitro and causes T cell lymphoma in New Zealand white rabbits. Here we
      demonstrate that HV(MNE) also immortalizes T cells from mustached tamarins but
      not those from owl monkeys, common marmosets, squirrel monkeys, black-capped
      capuchins, and humans. Cytogenetic and FACS analysis revealed the true origin and
      T cell lineage of the transformed tamarin T cell lines. Tamarin T cells contained
      HV(MNE) DNA sequence and displayed a decreased requirement for the IL-2 cytokine
      for growth. Thus, this EBV-like virus from M. nemestrina differs from the other
      EBV-like viruses found in nonhuman primates inasmuch as it appears to
      preferentially transform T cells.

PMID- 14698669
TI  - Formation of P10 tubular structures during AcMNPV infection depends on the
      integrity of host-cell microtubules.
AB  - During infection of insect cells with Autographa californica nucleopolyhedrovirus
      (AcMNPV), the very late protein P10 forms large fibrillar structures in the
      cytoplasm and nuclei of infected cells. In this study we have used confocal
      microscopy in association with a novel P10 antiserum to localise and study P10 in
      virus-infected cells. P10 was shown to be a component of tubular-like structures
      that spiralled throughout the cytoplasm and nucleus of AcMNPV-infected cells.
      These structures were observed to colocalise partly with cortical microtubules.
      When microtubules were depolymerised with the drug nocodazole, P10 tubules failed
      to form and the protein appeared concentrated in cytoplasmic foci. For the first
      time, we provide direct evidence using both antibody pulldown and yeast two
      hybrid experiments for the interaction of P10 with host-cell tubulin. It is
      suggested that this interaction may be a critical factor in AcMNPV-induced cell
      lysis.

PMID- 14698670
TI  - Promoter analysis of the Chilo iridescent virus DNA polymerase and major capsid
      protein genes.
AB  - The DNA polymerase (DNApol) and major capsid protein (MCP) genes were used as
      models to study promoter activity in Chilo iridescent virus (CIV). Infection of
      Bombyx mori SPC-BM-36 cells in the presence of inhibitors of DNA or protein
      synthesis showed that DNApol, as well as helicase, is an immediate-early gene and
      confirmed that the major capsid protein (MCP) is a late gene. Transcription of
      DNApol initiated 35 nt upstream and that of MCP 14 nt upstream of the
      translational start site. In a luciferase reporter gene assay both promoters were
      active only when cells were infected with CIV. For DNApol sequences between
      position -27 and -6, relative to the transcriptional start site, were essential
      for promoter activity. Furthermore, mutation of a G within the sequence TTGTTTT
      located just upstream of the DNApol transcription initiation site reduced the
      promoter activity by 25%. Sequences crucial for MCP promoter activity are located
      between positions -53 and -29.

PMID- 14698671
TI  - Full-length genome sequence of Mossman virus, a novel paramyxovirus isolated from
      rodents in Australia.
AB  - Mossman virus (MoV) was isolated on two occasions from wild rats trapped in
      Queensland, Australia, during the early 1970s. Together with Nariva virus and J
      virus MoV belongs to a group of novel paramyxoviruses isolated from rodents
      during the last 40 years, none of which had been characterized at the molecular
      level until now. cDNA subtraction strategies used to isolate virus-specific cDNA
      derived from both MoV-infected cells and crude MoV pellets were pivotal steps in
      rapid characterization of the complete genome sequence. Analysis of the full
      length genome and its encoded proteins confirmed that MoV is a novel member of
      the subfamily Paramyxovirinae which cannot be assigned to an existing genus. MoV
      appears to be more closely related to another unclassified paramyxovirus Tupaia
      paramyxovirus (TPMV), isolated from the tree shrew Tupaia belangeri. Together
      with Salem virus (SalV), a further unclassified paramyxovirus that was isolated
      from a horse, MoV and TPMV make up a new collection of paramyxoviruses situated
      evolutionally between the genus Morbillivirus and the newly established genus
      Henipavirus.

PMID- 14698672
TI  - An adenine-to-guanine nucleotide change in the IRES SL-IV domain of
      picornavirus/hepatitis C chimeric viruses leads to a nonviable phenotype.
AB  - The inability for the internal ribosomal entry site (IRES) of hepatitis C virus
      (HCV) to be readily studied in the context of viral replication has been
      circumvented by constructing chimeras such as with poliovirus (PV), in which
      translation of the genome polyprotein is under control of the HCV IRES. During
      our attempts to configure the PV/HCV chimera for our drug discovery efforts, we
      discovered that an adenine- (A) to-guanine (G) change at nt 350 in domain IV of
      the HCV IRES resulted in a nonviable phenotype. Similarly, a mengovirus (MV)/HCV
      chimera using the same configuration with a G at nt 350 (G-350) was found to be
      nonviable. In contrast, a bovine viral diarrhea virus (BVDV)/HCV chimera remained
      viable with G-350 in the HCV IRES insert. Second-site, resuscitating mutations
      were identified from the G-350 PV/HCV and MV/HCV viruses after blind passaging.
      For both viruses, the resuscitating mutations involved destabilization of domain
      IV in the HCV IRES. The nonviability of G-350 in the picornavirus/HCV chimeric
      background might be linked to translation efficiency as indicated by analyses
      with dual reporter and PV/HCV replicon constructs.

PMID- 14698673
TI  - Mutations in the RNA-binding domains of tombusvirus replicase proteins affect RNA
      recombination in vivo.
AB  - RNA recombination, which is thought to occur due to replicase errors during viral
      replication, is one of the major driving forces of virus evolution. In this
      article, we show evidence that the replicase proteins of Cucumber necrosis virus,
      a tombusvirus, are directly involved in RNA recombination in vivo. Mutations
      within the RNA-binding domains of the replicase proteins affected the frequency
      of recombination observed with a prototypical defective-interfering (DI) RNA, a
      model template for recombination studies. Five of the 17 replicase mutants tested
      showed delay in the formation of recombinants when compared to the wild-type
      helper virus. Interestingly, two replicase mutants accelerated recombinant
      formation and, in addition, these mutants also increased the level of subgenomic
      RNA synthesis (Virology 308 (2003), 191-205). A trans-complementation system was
      used to demonstrate that mutation in the p33 replicase protein resulted in
      altered recombination rate. Isolated recombinants were mostly imprecise
      (nonhomologous), with the recombination sites clustered around a replication
      enhancer region and a putative cis-acting element, respectively. These RNA
      elements might facilitate the proposed template switching events by the
      tombusvirus replicase. Together with data in the article cited above, results
      presented here firmly establish that the conserved RNA-binding motif of the
      replicase proteins is involved in RNA replication, subgenomic RNA synthesis, and
      RNA recombination.

PMID- 14698674
TI  - In vitro inhibition of fish rhabdoviruses by Japanese flounder, Paralichthys
      olivaceus Mx.
AB  - A homologous fish cell line stably expressing the recombinant Japanese flounder
      Mx (JFMx) was infected with hirame rhabdovirus (HIRRV) and viral hemorrhagic
      septicemia virus (VHSV), both of which are negative single-stranded RNA viruses
      belonging to the Rhabdoviridae family. Analysis of primary transcription of the
      two rhabdoviruses showed that there was lower expression level and copy number of
      the viral nucleoprotein transcript in the JFMx-transfected cell line than the
      infected, control cells, although no significant difference was observed. This
      suggests that JFMx may not be a potent inhibitor of rhabdoviral primary
      transcription. Kinetics of rhabdovirus expression by RT-PCR and quantitative real
      time RT-PCR showed reduced levels of the rhabdoviral glycoprotein and
      nucleoprotein transcripts over time, indicating the possible role of JFMx in
      blocking rhabdoviral replication by interfering with the transcription of the
      viral subgenomic mRNAs. Significant inhibition in rhabdovirus replication
      consequently resulted in the synthesis of fewer viral particles. This may explain
      why JFMx-expressing cells are less susceptible to virus-induced cell lysis, and
      thus, why they would have a significantly higher survival than the infected,
      control cells. These results provide direct evidence that JFMx has an antiviral
      effect in vitro.

PMID- 14698675
TI  - Alcoholism and obesity: overlapping neuropeptide pathways?
AB  - Ethanol is a caloric compound, and ethanol drinking and food intake are both
      appetitive and consummatory behaviors. Furthermore, both ethanol and food have
      rewarding properties. It is therefore possible that overlapping central pathways
      are involved with uncontrolled eating and excessive ethanol consumption. A
      growing list of peptides has been shown to regulate food intake and/or energy
      homeostasis. Peptides such as the melanocortins, corticotropin releasing factor,
      and cholecystokinin promote reductions of food intake while others such as
      galanin and neuropeptide Y stimulate feeding. The present review highlights
      research aimed at determining if ingestive peptides also regulate voluntary
      ethanol intake, with an emphasis on the melanocortins and neuropeptide Y. It is
      suggested that research directed at ingestive peptides may expand our
      understanding of the neurobiological mechanisms that drive ethanol self
      administration, and may reveal new therapeutic candidates for treating alcohol
      abuse and alcoholism.

PMID- 14698676
TI  - MTII-induced reduction of voluntary ethanol drinking is blocked by pretreatment
      with AgRP-(83-132).
AB  - Over the last 30 years, evidence has emerged indicating that the central
      melanocortin (MC) peptide system is involved with neurobiological responses to
      drugs of abuse. Recently, rats selectively bred for high ethanol preference were
      shown to have altered brain levels of MC receptor (MCR) and central infusion of
      the potent non-selective MCR agonist, melanotan-II (MTII), attenuates their high
      ethanol drinking. The goal of the present report was to further characterize the
      effects of MTII on voluntary ethanol consumption. In alcohol preferring C57BL/6
      mice with an established history of ethanol drinking, intracerebroventricular
      (i.c.v.) infusion of a 5.0 microg dose of agouti-related protein (AgRP)-(83-132),
      a non-selective MCR antagonist, has no effect on 8-h ethanol drinking or food
      intake. However, pre-treatment with a 5.0 microg dose of (AgRP)-(83-132)
      significantly blocks MTII-induced (1.0 microg) reduction of 8-h ethanol drinking
      and food intake, consistent with a competitive antagonist action. I.c.v. infusion
      of MTII does not cause alteration of blood ethanol levels 2- or 4-h following
      intraperitoneal (i.p.) injection of a 4.0 g ethanol/kg dose. Finally, when given
      in an i.p. injection, a 150 microg dose of MTII reduces 8-h ethanol drinking.
      These data extend recent findings by showing that both central and peripheral
      administration of MTII reduces ethanol drinking by mice. Additionally, the
      ability of (AgRP)-(83-132) to block the effects of MTII implies that MTII-induced
      reduction of ethanol drinking is receptor mediated.

PMID- 14698677
TI  - Cardiovascular and behavioural effects induced by naloxone-precipitated morphine
      withdrawal in rat: characterization with tachykinin antagonists.
AB  - This study examined the intracerebroventricular (i.c.v.) effects of three
      selective tachykinin receptor antagonists on the cardiovascular and behavioural
      responses induced by naloxone-precipitated morphine withdrawal in rats. I.c.v.
      injection of naloxone (10 microg) to morphine pre-treated rats (i.c.v. for 5
      days) induced an immediate increase in blood pressure ( approximately 10 mmHg)
      and behavioural activity (sniffing > rearing > face washing approximately
      grooming approximately wet dog shake) without causing significant heart rate
      changes. The prior i.c.v. injection of the NK(1) receptor antagonist (6.5 nmol
      LY306740) reduced face washing and grooming during morphine withdrawal. NK(2) and
      NK(3) receptor antagonists (6.5 nmol SR48968 and R820) did not affect behavioural
      effects, yet the co-injection of the three tachykinin antagonists reduced all
      behavioural activity. The pressor response was not affected by the selective
      inhibition of NK(1) and NK(3) receptors while both blood pressure and heart rate
      were markedly enhanced by SR48968 during morphine withdrawal. The potentiating
      effect of SR48968 was prevented following simultaneous blockade of the three
      tachykinin receptors. In addition to confirming the involvement of central
      tachykinins in behavioural manifestations to morphine withdrawal, data suggest a
      modulatory function for tachykinins, especially the NK(2) receptor, in brain
      autonomic control of blood pressure and heart rate in supraspinal noloxone
      precipitated withdrawal.

PMID- 14698678
TI  - Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and
      interleukin 6 by rat leukocyte subpopulations after exposure to substance P.
AB  - The interaction between components of the nervous system and multiple target
      cells in the cutaneous immune system has been receiving increasing attention.
      Recently, the involvement of neuropeptides has been demonstrated to play an
      important role in the inflammatory cascade. Neuropeptides such as Substance P are
      released by cutaneous neurons and modulate the function of immunocompetent and
      inflammatory cells as well as epithelial and endothelial cells. Substance P has
      been shown to function as a mediator for cell proliferation, cytokine production,
      and as an upregulator of various cell surface receptors. In this study, we show
      the effect of Substance P on the production of Tumor Necrosis Factor-alpha,
      Interleukin 1-beta, Interleukin 2, and Interleukin 6 by T-lymphocytes,
      macrophages and neutrophils. These data demonstrate that pathophysiological
      levels of Substance P induce production of cytokines in all three cell
      populations tested. Interestingly, T-cells demonstrated the highest percentage of
      cells expressing all four cytokines. In contrast, macrophages and neutrophils
      produced the highest absolute levels of cytokines. The elucidation of mediating
      mechanisms of Substance P activation of leukocytes is crucial to the
      understanding of the cutaneous inflammatory cascade and involvement of the
      peripheral nervous system on the immune system. These findings suggest that
      Substance P participates in the complex network of mediators that regulate
      cutaneous inflammation and potentially the rate of wound healing.

PMID- 14698679
TI  - Modulation of sympathetic activity by corticotropin-releasing hormone and atrial
      natriuretic peptide.
AB  - BACKGROUND: Heart rate variability represents a reliable marker to delineate the
      status of autonomic nervous system (ANS) function and alterations due to stress
      in vivo. Interestingly, up to now the effects of corticotropin-releasing hormone
      (CRH), a key regulator of the stress hormone system, upon heart rate variability
      are not sufficiently described. Hence, we attempted to investigate the ANS
      effects of a CRH bolus and the modulatory influences of atrial natriuretic
      peptide (ANP), one of the most important functional antagonist of CRH actions.
      METHODS: 12 healthy male volunteers were administered 100 microg CRH as bolus
      injection at 15:00. Six randomly chosen subjects received 150 microg ANP
      dissolved in normal saline and six subjects a normal saline infusion from 14:45
      to 15:15. From 13:00 to 17:00 an ECG was recorded and mean heart rate (HR), total
      power (TP), very low frequency (VLF), low frequency (LF), LF in normalized units
      (LF [nu]), high frequency (HF) domains and the LF/HF-ratio in the interval from
      14:00 to 16:00 were determined. RESULTS: After administration of CRH a
      significant increase in HR and a fast reduction of TP were observed, which lasted
      about 1 h. Based upon spectral domain analyses the sympathetic activity after CRH
      administration as indicated by LF [nu] increased by 31% (mean location) during
      saline. Applying ANP this increase was reduced to 19% (mean location). The VLF
      component, which is considered to be based in part also on sympathetic
      influences, indicates comparable effect. During saline the VLF after CRH bolus
      remained largely unchanged, but was reduced to 66% by ANP. Though the vagal
      activity indicated by the HF component was reduced after CRH, no significant
      differences emerged between both treatments. The changes of the LF/HF-ratio were
      pronounced in both groups. During saline this ratio increased by about 111%,
      during ANP only by 43% (mean location). CONCLUSIONS: Based upon HRV analysis the
      CRH administration induced sympathotonic effects which were antagonized by ANP.
      The observed vagal changes were less pronounced and need further investigation.
      Further studies of autonomic effects by alterations of CRH secretion in
      depression and anxiety disorder are strongly warranted.

PMID- 14698680
TI  - Microinjection of CART peptide 55-102 into the nucleus accumbens blocks
      amphetamine-induced locomotion.
AB  - The role played by the biologically active CART 55-102 peptide in NAcc AMPH
      induced locomotion was investigated. When microinjected alone into this site,
      none of the doses of CART 55-102 tested (0.1, 0.4, 1.0 or 2.5 microg/0.5
      microl/side) produced effects on locomotion during a two-h test. However, when co
      injected with AMPH (2.5 microg/0.5 microl/side) into the NAcc, moderately high
      (2.5 microg/side) and middle to high (0.4-2.5 microg/side) doses of CART 55-102
      significantly attenuated the effects of AMPH on locomotion and rearing,
      respectively. These results indicate that CART peptides can exert an antagonistic
      effect on the generation of locomotion by AMPH in the NAcc.

PMID- 14698681
TI  - The cholecystokinin system in the rat retina: receptor expression and in vivo
      activation of tyrosine phosphorylation pathways.
AB  - High levels of endogenous cholecystokinin (CCK) are present in the rat retina and
      restricted to amacrine cells. Two types of CCK receptors exist but their
      expression and intracellular transduction pathways coupled in the rat retina are
      unknown. The aims of this study were to investigate CCK receptors expression in
      rat retina and to study downstream tyrosine phosphorylation pathways. For this
      purpose, total mRNA isolated from rat retina was subjected to RT-PCR analysis.
      Isolated rat retinas were incubated in presence of CCK. Soluble proteins in
      retinal homogenates were immunoprecipitated with anti-phoshpotyrosine or anti
      p130(Cas) specific monoclonal antibodies and subjected to SDS-PAGE, followed by
      Western blotting analysis. Both types of CCK receptor mRNAs, A and B, are present
      in the rat retina. Incubation of retina with CCK induced a rapid increase in
      several phosphotyrosine-containing bands with molecular masses greater than 30
      kDa. Western Blotting and immunoprecipitation with a specific monoclonal antibody
      identified one of the phosphotyrosine bands as the adapter protein p130(Cas).
      Tyrosine phosphorylation of p130(Cas) induced by CCK in rat retina was time and
      concentration dependent: CCK induced tyrosine phosphorylation of p130(Cas)
      occurred rapidly with the maximum effect observed at 2.5 min incubation with 1
      microM CCK. Our data clearly identified CCK-A and CCK-B receptor mRNAs in the rat
      retina and demonstrated that they are functional, stimulating tyrosine
      phosphorylation pathways. Our results provide novel biochemical information to
      further understand the physiological role of CCK A and B receptors in rat retina.

PMID- 14698683
TI  - The paleobiology of Amphipithecidae, South Asian late Eocene primates.
AB  - Analysis of the teeth, orbital, and gnathic regions of the skull, and fragmentary
      postcranial bones provides evidence for reconstructing a behavioral profile of
      Amphipithecidae: Pondaungia, Amphipithecus, Myanmarpithecus (late middle Eocene,
      Myanmar) and Siamopithecus (late Eocene, Thailand). At 5-8 kg, Pondaungia,
      Amphipithecus, and Siamopithecus are perhaps the largest known Eocene primates.
      The dental and mandibular anatomy suggest that large-bodied amphipithecids were
      hard-object feeders. The shape of the mandibular corpus and stiffened symphysis
      suggest an ability to resist large internal loads during chewing and to recruit
      significant amounts of muscle forces from both the chewing and non-chewing sides
      of the jaw so as to increase bite force during mastication. The large spatulate
      upper central incisor of Pondaungia and projecting robust canines of all the
      larger amphipithecids suggest that incisal food preparation was important. The
      molars of Siamopithecus, Amphipithecus, and Pondaungia have weak shearing crests.
      This, and the thick molar enamel found in Pondaungia, suggests a diet of seeds
      and other hard objects low in fiber. In contrast, Myanmarpithecus was smaller,
      about 1-2 kg; its cheek teeth suggest a frugivorous diet and do not imply seed
      eating. Postcranial bones (humerus, ulna, and calcaneus) of a single large
      amphipithecid individual from Myanmar suggest an arboreal quadrupedal locomotor
      style like that of howler monkeys or lorises. The humeral head is rounded,
      proximally oriented, and the tuberosities are low indicating an extremely mobile
      glenohumeral joint. The great thickness of the midshaft cortical bone of the
      humerus implies enhanced ability to resist bending and torsion, as seen among
      slow moving primate quadrupeds. The elbow joint exhibits articular features for
      enhanced stability in habitually flexed positions, features also commonly found
      in slow moving arboreal quadrupeds. The short distal load arm of the calcaneus is
      consistent with, but not exclusive to, slow, arboreal quadrupedalism, and
      suggests no reliance on habitual leaping.

PMID- 14698684
TI  - New discoveries and interpretations of hominid fossils and artifacts from Vindija
      Cave, Croatia.
AB  - Beginning with excavations during the 1970s, Vindija Cave (Croatia) has yielded
      significant Middle and Upper Paleolithic fossil and archaeological finds. We
      report on seven recently identified hominid fossils, a newly associated partial
      hominid cranial vault from level G(3), nine possible bone retouchers, and a
      revised interpretation of the Mousterian artifact assemblage from the site. This
      new information reinforces our knowledge of the complex biocultural phenomena
      revealed in unit G and earlier deposits at Vindija. Six of the new hominid
      fossils derive from stratigraphic units G and I, while one lacks exact
      provenience. All specimens preserving diagnostic anatomy are from Neandertals.
      One of the postcranial remains, a radius fragment which exhibits Neandertal-like
      anatomy, comes from level G(1)and is congruent with the previously established
      association of Neandertals with an early Upper Paleolithic industry at the site.
      The partial cranial vault represents the most complete Neandertal from Vindija.
      The possible retouchers derive from unit G. Our analysis of these artifacts
      suggests that both percussion and pressure techniques may have been used by
      Neandertals in the final stage of tool production (retouching). This paper also
      presents a revision of the artifact analysis for late Mousterian level G(3). We
      separated raw materials into two main groups due to the differing ways that the
      materials fracture and the differing morphology of the debitage. The use of raw
      material in level G(3)is different from earlier Middle Paleolithic levels at
      Vindija. This indicates that the G(3)late Neandertals were making choices
      regarding source material somewhat more like the Upper Paleolithic people at the
      site. When interpreted within a larger regional framework, the Vindija
      archaeological and hominid fossil remains demonstrate a complex, mosaic pattern
      of biocultural change in the Late Pleistocene of south-central Europe.

PMID- 14698685
TI  - Nacholapithecus skeleton from the Middle Miocene of Kenya.
AB  - An almost entire skeleton of a male individual of Nacholapithecus kerioi (KNM-BG
      35250) was discovered from Middle Miocene (approximately 15 Ma) sediments at
      Nachola, northern Kenya. N. kerioi exhibits a shared derived subnasal morphology
      with living apes. In many postcranial features, such as articular shape, as well
      as the number of the lumbar vertebrae, N. kerioi resembles Proconsul heseloni
      and/or P. nyanzae, and lacks suspensory specializations characteristic of living
      apes. Similarly, N. kerioi shares some postcranial characters with Kenyapithecus
      spp. However, despite the resemblance, N. kerioi and Proconsul spp. are quite
      different in their body proportions and some joint morphologies. N. kerioi has
      proportionally large forelimb bones and long pedal digits compared to its
      hindlimb bones and lumbar vertebrae. Its distinctive body proportions suggest
      that N. kerioi was more derived for forelimb dominated arboreal activities than
      P. nyanzae and P. heseloni. On the other hand, it exhibits a mixture of derived
      and primitive cranio-dental and postcranial features relative to the
      contemporaneous Kenyapithecus and Early MioceneMorotopithecus. While the
      phylogenetic position of N. kerioi is unsettled, it seems necessary to posit
      parallel evolution of cranio-dental and/or postcranial features in fossil and
      living apes.

PMID- 14698686
TI  - Oreopithecus bambolii: an unlikely case of hominid-like grip capability in a
      Miocene ape.
AB  - Oreopithecus bambolii, an ape from the late Miocene of Italy, is said to possess
      a hand capable of a precision grip like that of humans. Relative hand length,
      proportions of the thumb, and morphological features of the thumb and wrist were
      adduced to support the idea that Oreopithecus had a hand that closely matched the
      pattern in Australopithecus. A reappraisal of earlier arguments and comparisons
      of Oreopithecus with humans, apes, and Old World monkeys, reveals that
      Oreopithecus had an essentially ape-like hand that emphasized ape-like power
      grasping over human-like precision grasping.

PMID- 14698687
TI  - Knowing the limits of one's understanding: the development of an awareness of an
      illusion of explanatory depth.
AB  - Adults overestimate the detail and depth of their explanatory knowledge, but
      through providing explanations they recognize their initial illusion of
      understanding. By contrast, they are much more accurate in making self
      assessments for other kinds of knowledge, such as for procedures, narratives, and
      facts. Two studies examined this illusion of explanatory depth with 48 children
      each in grades K, 2, and 4, and also explored adults' ratings of the children's
      explanations. Children judged their understanding of mechanical devices (Study 1)
      and procedures (Study 2). Second and fourth graders showed a clear illusion of
      explanatory depth for devices, recognizing the inaccuracy of their initial
      impressions after providing explanations. The illusion did not occur for
      knowledge of procedures.

PMID- 14698688
TI  - A timing-specific memory distortion effect in young children.
AB  - It has been suggested that there are systematic distortions in children's memory
      for temporal durations, such that children's memory is not just less accurate
      than that of adults but qualitatively different. Experiment 1 replicated the
      memory distortion effect by demonstrating developmental change in the tendency to
      confuse a reference duration with one that is shorter rather than longer than it.
      When the long-term memory demands of the task were reduced by providing reminders
      of the reference duration on every trial, there were no such qualitative changes
      in error patterns (Experiment 2). Further evidence for developmental changes in
      memory distortion was found in the temporal generalization task of Experiment 3,
      in which stimuli were spaced logarithmically rather than linearly. In Experiment
      4, a similar distortion pattern was absent in a task in which children made
      judgments about the pitch rather than the duration of stimuli, suggesting the
      effect may be specific to time estimation.

PMID- 14698689
TI  - Magnitude comparison in preschoolers: what counts? Influence of perceptual
      variables.
AB  - This study examined numerosity comparison in 3-year-old children. Predictions
      derived from the analog numerical model and the object-file model were contrasted
      by testing the effects of size and ratio between numerosities to be compared.
      Different perceptual controls were also introduced to evaluate the hypothesis
      that comparison by preschoolers is based on correlated perceptual variables
      rather than on number per se. Finally, the relation between comparison
      performance and verbal counting knowledge was investigated. Results showed no
      evidence that preschoolers use an analog number magnitude or an object-file
      mechanism to compare numerosities. Rather, their inability to compare sets
      controlled for surface area suggests that they rely on perceptual cues.
      Furthermore, the development of numerosity-based representations seems to be
      related to some understanding of the cardinality concept.

PMID- 14698690
TI  - From the epilepsy foundation.

PMID- 14698691
TI  - When did neurologists and psychiatrists stop talking to each other?
AB  - Patients with epilepsy have a significantly higher prevalence of psychiatric
      comorbid disorders involving depression, anxiety, psychotic, and attention
      deficit disorders. Accordingly, one would expect that psychiatrists would be
      actively involved in the evaluation and management of these patients. This,
      however, is hardly the case. Patients who undergo temporal lobectomies, for
      example, are known to experience postsurgical depression and occasionally
      psychotic disorders. Yet, most epilepsy centers in North America do not include a
      psychiatric evaluation as part of the presurgical work-up. Collaboration between
      epileptologists and psychiatrists is often sparse, despite the intimate
      relationship between psychiatric comorbidities and epilepsy. The purpose of this
      paper is to highlight this bizarre phenomenon and to identify some of the reasons
      behind it.

PMID- 14698692
TI  - Regulation, religious experience, and epilepsy: a lens on complementary
      therapies.
AB  - Complementary and alternative medical (CAM) therapies include chiropractic,
      acupuncture and traditional Oriental medicine, massage therapy, and herbal
      remedies; mind-body therapies (such as meditative practices and visualization);
      and folk practices and religious healing. Of these, modalities based on spiritual
      healing create a number of conundrums for the clinician, including legal,
      regulatory, and ethical issues. Further, the historic relationship between the
      study of epilepsy and religious experience suggests particular, potential
      associations between CAM therapies (and especially spiritual healing) and care
      for epileptic patients. There are at least two dimensions to this exploration:
      first, the widespread use of spiritual healing for treatment of epilepsy; and
      second, the hypothesized connection between epileptic seizures and mystical
      states. A number of legal rules help address potential abuse of authority by
      health care professionals, and include: (1) medical licensure; (2) scope of
      practice; (3) professional discipline; (4) malpractice; and (5) fraud. This
      article offers a preliminary resource for clinicians interested in these topics.

PMID- 14698693
TI  - Callosal lesions and behavior: history and modern concepts.
AB  - Callosotomy has played a unique role in the treatment of epilepsy and in the
      understanding of human brain function. The pioneering work of Dejerine and
      Liepmann presenting the first findings of callosal lesion pathology at the turn
      of the 20th century was accepted but then quickly forgotten. Two schools
      resurrected the phoenix of callosal syndromes: Roger Sperry and Michael Gazzaniga
      leading in experimental neuroscience, and Norman Geschwind leading in clinical
      neurology. Callosotomy remains an effective technique to treat atonic, tonic, and
      tonic-clonic seizures, especially in patients with symptomatic generalized
      epilepsies such as Lennox-Gastaut syndrome. Neurologic, cognitive, and behavioral
      complications limit its use given that precise characterization of these
      complications as well as their frequency is difficult. The high frequencies of
      developmental delays, severe seizures, head injuries, antiepileptic drug burden,
      and other factors limit the ability to attribute a specific change to surgical
      intervention, since surgery can change multiple factors. For example, subtle
      behavioral changes in executive function and personality are difficult to
      delineate in a population with preexisting neurologic and psychiatric disorders.
      Despite this, a clearer picture of the effects of callosotomy, as defined by
      clinical neurology and neuropsychology as well as cognitive neuroscience, is
      emerging.

PMID- 14698694
TI  - Mapping form and function in the human brain: the emerging field of functional
      neuroimaging in cortical malformations.
AB  - Malformations of cortical development (MCDs) are increasingly being recognized as
      a common cause of epilepsy in cases previously felt to be cryptogenic. MCDs occur
      when the normal process of cerebral cortical development is disrupted, and
      include disorders of neuronal proliferation, migration, and organization. Many
      have a genetic basis and the genes responsible for some MCDs have been
      identified. MCDs represent a unique and valuable substrate in functional brain
      mapping studies, since as developmental lesions they provide complementary
      information to studies performed on patients with acquired brain lesions. In
      recent years an increasing number of functional neuroimaging methods, including
      positron emission tomography, single photon emission computed tomography,
      magnetic resonance spectroscopy, and functional magnetic resonance imaging, have
      been applied to patients with MCDs. In this review we highlight some of the
      prominent findings in this emerging field by presenting the functional
      neuroimaging characteristics of selected MCDs.

PMID- 14698695
TI  - Health-related quality of life in senior adults with epilepsy: what we know from
      randomized clinical trials and suggestions for future research.
AB  - OBJECTIVE: The goal of this work was to review the randomized controlled trial
      (RCT) literature on antiepileptic medication effects on health-related quality of
      life in seniors with epilepsy. METHODS: Studies published from 1998 to June 2002
      were identified by searching through Medline and the Cochrane Clinical Trials
      Register. Pre-1998 RCTs identified by Baker et al. [Epilepsia 41 (2003) 1357]
      were also examined for relevance to the present review. Studies were reviewed if
      they included a RCT design and included epilepsy patients over the age of 60.
      RESULTS: A total of 85 clinical trials were reviewed. Of the 85 studies reviewed
      only 37 RCT studies included patients over the age of 60. However, formal quality
      of-life outcome assessment was not performed in any of the RCTs that included
      senior adults, and only six studies provided formal quantitative analyses of AED
      effects in the form of adverse events incidence and participant withdrawal rates.
      For the most part, early study withdrawal rates were substantial for seniors and
      adverse events were very common. Two studies reporting on the cognitive and
      behavioral effects of study AEDs indicated only modest impact when AED
      monotherapy was kept at therapeutic levels. CONCLUSIONS: Despite growing
      appreciation for quality-of-life, issues in the management of epilepsy little
      current empirical guidance is available for elderly with epilepsy. There exists
      virtually no information on elderly patient preferences and goals for epilepsy
      treatment outcomes, and available data primarily concerns younger adults. Despite
      some encouraging preliminary evidence from this review suggesting that
      conservative AED treatment may have a more favorable quality of life-related
      outcome, more conclusive statements await further systematic investigation.

PMID- 14698696
TI  - The expression of interictal, preictal, and postictal facial-wiping behavior in
      temporal lobe epilepsy: a neuro-ethological analysis and interpretation.
AB  - By videotape recordings analysis we investigated the frequencies of interictal,
      preictal, and postictal wiping or rubbing movements targeting the face region
      (face wiping, FW) in 17 right and 13 left mesial temporal lobe epilepsy (MTLE)
      patients. Patients' data were compared with FW frequencies obtained in 22 healthy
      controls listening to a presentation. Results showed that: (1) FW movements were
      present in both controls and patients; however, the patient groups showed lower
      interictal and preictal FW rates relative than controls; (2) right and left
      temporal lobe seizures were followed by a marked increase in the expression of
      wiping activities directed to the nose as well as to other face regions with
      respect to the interictal-preictal period; (3) during the first 5min postictal FW
      was performed preferentially with the hand ipsilateral to the seizure focus; (4)
      postictal examination of the patient by an observer, especially if of the
      opposite sex, resulted in a higher incidence of FW acts. After temporal lobe
      seizures there is an exaggerated expression of movements targeting the face
      region, and not exclusively directed to the nose. According to an ethological
      interpretation of the FW behavior as a motor behavior present throughout the
      phylogenetic scale, from rodents to primates, we suggest the postictal emergence
      of an innate action pattern modulated by external emotional-cognitive stimuli.

PMID- 14698697
TI  - Posttraumatic stress disorder, dissociation, and sexual abuse history in
      epileptic and nonepileptic seizure patients.
AB  - Rates of posttraumatic stress disorder (PTSD), dissociative symptoms, and
      childhood sexual abuse (CSA) are believed to be higher among patients with
      nonepileptic seizures (NES) than those with epileptic seizures (ES). However,
      women have higher rates of CSA and sexual assault than men. Comparisons of
      seizure type controlling for gender may produce different results. Data from an
      opportunity sample of 34 patients with ES and 17 with NES evaluated during or
      following phase 1 video-EEG monitoring demonstrated that patients with NES had
      statistically higher rates of PTSD and CSA and higher Dissociative Experiences
      Scale (DES) scores than patients with ES. No differences were found between women
      with NES and ES for histories of PTSD or CSA. Mean between-group DES score
      differences remained. Results indicated that PTSD, dissociation, and CSA may be
      common among women presenting to a tertiary epilepsy referral center for both ES
      and NES. Neither a positive history of CSA nor a history of PTSD was evidence
      against epilepsy.

PMID- 14698698
TI  - Sleep disturbance in children with epilepsy.
AB  - This study employed a validated pediatric sleep questionnaire to evaluate for
      sleep-disordered symptoms in children with epilepsy (n=14). Results were compared
      with those for age-matched children (n=14) with known obstructive sleep apnea.
      Subjects were enrolled from an outpatient epilepsy clinic and a pediatric sleep
      disorders clinic. We hypothesized that children with epilepsy would (1) report
      symptoms of sleep disturbance similar to those of children with documented
      obstructive sleep apnea, and (2) display behavioral disturbances on parent and
      child behavioral symptom measures. Results indicate that more than 50% of
      children with epilepsy had behavioral problems (n=14). No differences in snoring,
      excessive daytime sleepiness, and restless sleep were seen between the two
      subject groups. Results suggest that neurobehavioral problems in children with
      epilepsy may in part be attributed to an underlying sleep disturbance.

PMID- 14698699
TI  - Lamotrigine monotherapy compared with carbamazepine, phenytoin, or valproate
      monotherapy in patients with epilepsy.
AB  - OBJECTIVE: This open-label study evaluated the efficacy and tolerability of
      lamotrigine monotherapy compared with monotherapy with conventional antiepileptic
      drugs in patients converting from previous monotherapy because of inadequate
      seizure control or unacceptable side effects. METHODS: This study was conducted
      in 26 neurology clinics and epilepsy centers throughout the United States. The
      study enrolled 115 patients with epilepsy converting from previous monotherapy
      because of inadequate seizure control or unacceptable side effects. Patients were
      randomized 1:1 to receive 24 weeks of lamotrigine monotherapy or monotherapy with
      a conventional antiepileptic drug (carbamazepine, phenytoin, or valproate based
      on physician's choice). Patients were converted during an </=8-week
      Escalation/Taper Phase from their prestudy antiepileptic drug (carbamazepine,
      phenytoin, or valproate) to lamotrigine via a protocol-specified dosing algorithm
      or to conventional therapy via standard dosing guidelines. After monotherapy was
      achieved, patients continued in the study for a 24-week Maintenance Phase.
      RESULTS: More lamotrigine patients (65%) than conventional therapy patients (57%)
      completed the 24-week Maintenance Phase (primary efficacy endpoint). The mean
      time to withdrawal from the study was 175 days (SD=83.1) for lamotrigine patients
      compared with 156 days (SD=80.7) for conventional therapy patients. Adverse
      events, the most common reason for discontinuing the Maintenance Phase, accounted
      for 16% of withdrawals among lamotrigine patients compared with 26% of
      withdrawals among conventional therapy patients. The mean reduction in seizure
      frequency was 53% (SD=55.1) for patients using lamotrigine compared with 32%
      (SD=149.9) for patients using conventional therapy. Humanistic measures including
      investigator global assessment, the patient self-assessment, and QOLIE-31 scores
      show that lamotrigine monotherapy was perceived by both physicians and patients
      to have benefits over monotherapy with conventional antiepileptic drugs.
      CONCLUSIONS: Converting from monotherapy with a less effective or poorly
      tolerated conventional antiepileptic drug to monotherapy with lamotrigine is
      associated with better clinical and humanistic outcomes than converting to an
      alternative conventional antiepileptic drug.

PMID- 14698700
TI  - Partial epilepsy with "ecstatic" seizures.
AB  - Reports focusing on auras of ecstasy or pleasure have been limited largely to
      single case descriptions. We examined 11 consecutive patients with such ictal
      symptoms. Eight had sensory hallucinations, four had erotic sensations, five
      described "a religious/spiritual experience," and several had symptoms that were
      felt to have no counterpart in human experience. Ictal EEG recordings were
      performed in four patients; two had seizure onset in the right temporal lobe and
      two in the left. In seven the onset could not be definitely localized. The
      diagnosis of epilepsy was often delayed. Eight patients wished to experience
      seizures; self-induction was possible in five and four showed treatment
      noncompliance. In patients with insufficient drug intake, in whom good compliance
      should be expected, it is relevant to consider seizures with pleasant
      symptomatology. According to the literature, experiential and ecstatic seizures
      seem to have had a substantial impact on our cultural and religious history.

PMID- 14698701
TI  - Antidepressive treatment in patients with temporal lobe epilepsy and major
      depression: a prospective study with three different antidepressants.
AB  - Major depression (MD) is underdiagnosed and undertreated in patients with
      temporal lobe epilepsy (TLE). Side effects of some antidepressants, like
      increased risk of seizures and drug-drug interactions with anticonvulsants,
      contribute to undertreatment of MD in patients with TLE. We analyzed post hoc the
      data from 2 years of treatment of inpatients with MD and TLE. Seventy-five
      patients received standard treatment with citalopram, mirtazapine, or reboxetine,
      respectively, at recommended dosage. Examinations were done with the Hamilton
      Rating Scale for Depression at admission and after 4 and 20-30 weeks. Plasma
      levels of anticonvulsants were examined at admission and discharge. Seizures were
      documented. The antidepressive treatment was efficacious in all antidepressant
      groups. No case of serious adverse event or drug interaction occurred. There was
      no increase in frequency or severity of seizures. At endpoint the dropout rate
      for mirtazapine was significantly higher than that for reboxetine or citalopram.
      Reboxetine showed a trend to be more efficacious than citalopram but not
      mirtazapine at Week 4.

PMID- 14698703
TI  - The localizing value of auditory event-related potentials (P300) in patients with
      medically intractable temporal lobe epilepsy.
AB  - The localizing value of postictal versus interictal event-related potentials
      (ERPs) was studied in patients with medically intractable TLE admitted for long
      term video EEG monitoring. Ten patients with partial seizures and secondary
      generalization underwent preictal (upon hospital admission), postictal (</=6h
      after seizure), and interictal (7-48h after seizure) ERP recordings of an
      auditory oddball paradigm. Preictal ERPs were compared to postictal and
      interictal recordings. Intraclass correlations, transformed into z scores, were
      utilized to analyze amplitude differences between electrodes placed on the
      hemisphere ipsilateral versus contralateral to the epileptogenic focus. The
      results showed that in 9 out of 10 patients the ERP amplitude was reduced in
      postictal compared to preictal recordings for electrodes placed ipsilateral to
      the epileptogenic focus (P<0.0001). However, there was no difference in amplitude
      between ipsilateral and contralateral electrodes in preictal and interictal
      recordings. These findings suggest that postictal ERPs are of localizing value in
      patients with TLE while interictal ERPs are not.

PMID- 14698702
TI  - Validation of the quality of life in childhood epilepsy questionnaire in American
      epilepsy patients.
AB  - The aim of this study was to adapt the Australian Quality of Life in Childhood
      Epilepsy Questionnaire (QOLCE) and determine its psychometric properties in a
      North American population. Participants were North American families with
      children diagnosed with epilepsy. Parents were asked to complete the American
      QOLCE (USQOLCE) and the Child Health Questionnaire (CHQ). Seventy-one families
      completed the USQOLCE. The internal consistency reliability of the subscales was
      good. USQOLCE subscales correlated highly with theoretically similar subscales
      contained in the CHQ. Theoretically dissimilar subscales on the two instruments
      did not correlate as well. USQOLCE correlated significantly with a parental
      rating of seizure severity and an independent measure of degree of postoperative
      seizure control. This study demonstrated that the USQOLCE is suitable for a North
      American population with evidence of its reliability and validity including its
      sensitivity to seizure burden.

PMID- 14698704
TI  - Use of levetiracetam in a population of patients aged 65 years and older: a
      subset analysis of the KEEPER trial.
AB  - Levetiracetam (Keppra) was evaluated in a subset of patients aged >/=65 years
      (n=78) enrolled in a large (n=1030) open-label, phase IV trial (the KEEPER
      trial). A 4-week dose adjustment was followed by a 12-week evaluation period. An
      overall median reduction in partial seizures of 80.1% (n=65) was observed.
      Overall, 76.9% of patients were >/=50% responders, 56.9% were >/=75% responders,
      and 40.0% were 100% responders. Levetiracetam was well tolerated, with 42.3% of
      patients reporting one or more adverse events. A total of 15 patients (19.2%)
      experienced an adverse event that led to discontinuation. Somnolence (n=13,16.7%)
      and dizziness (n=7,9.0%) were the most commonly reported adverse events. Despite
      the limitations of the open-label study design, these data provide information
      regarding the use of levetiracetam as add-on therapy for the treatment of partial
      onset seizures in patients >/=65 years of age, including those requiring
      concomitant medications.

PMID- 14698705
TI  - Compliance and satisfaction with switching from an immediate-release to sustained
      release formulation of valproate in people with epilepsy.
AB  - OBJECTIVE: The goal of our work was to assess compliance and patient satisfaction
      with switching from sodium valproate to Depakine Chrono in patients with
      epilepsy. METHODS: Clinical, demographic, and behavioral details assessing
      compliance and satisfaction were collected using self-completion questionnaires
      at the time of inclusion in the study and 3 months after the inclusion day.
      RESULTS: Data were collected from 2031 respondents from eight European countries.
      There were significant differences between time 1 and time 2 of the study in
      seizure frequency, reported side effects, compliance, and patient satisfaction.
      CONCLUSION: Findings suggest that switching from sodium valproate to Depakine
      Chrono results in an increase in seizure-free rates, a reduction in reported side
      effects, an improvement in the level of compliance, and a modest improvement in
      patient satisfaction.

PMID- 14698706
TI  - Mesial temporal lobe epilepsy and hippocampal sclerosis: cognitive function
      assessment in Hispanic patients.
AB  - PURPOSE: The goal of this study was to assess the cognitive function status in
      patients with mesial temporal lobe epilepsy and hippocampal sclerosis (TLE+HS) to
      determine their cognitive function profile and to correlate material-specific
      memory deficits with HS laterality diagnosed by MRI. METHODS: Seventy-one
      patients were assessed with a neuropsychological protocol that includes IQ,
      attention, handedness, verbal memory, visual memory, language, and the executive
      function. chi(2) and correlation tests were used. RESULTS: Memory impairment was
      found in 46 patients (66%): patients without any memory deficit (n=25), patients
      with verbal memory deficit (n=21), patients with visual memory deficit (n=17),
      patients with deficit for both types of memory (n=8). Correlation between MRI
      lesion and memory was 66%. Language was impaired in 33 patients (46%). Eighteen
      patients (25%) had a deficit of the executive function. CONCLUSIONS: Patients
      with TLE+HS presented with a deficit in material-specific episodic memory
      correlating in large proportion with HS lateralization. We also found language
      and executive function impairments.

PMID- 14698707
TI  - Epilepsy surgery outcome among US veterans.
AB  - We retrospectively studied the outcome of anterior temporal lobectomy (ATL) among
      a population of veterans and evaluated outcome related to comorbidities. Veterans
      who underwent ATL between 1990 and 2001 at the Veterans Administration Hospital
      in Madison, Wisconsin, were included. Data related to postoperative seizure
      outcome, quality of life outcome, and employment outcome were collected. Factors
      associated with favorable outcome and outcome related to comorbidities were
      evaluated. Twenty-seven patients were entered into the study. The mean age at
      onset of seizures was 25 years (+/-10.2). History of a non-substance abuse
      psychiatric diagnosis, and substance abuse was present in 26% (7/27) and 30%
      (9/27), respectively, prior to surgery. While 66.6% (18/27) had a good outcome
      (Engel's Class I), no difference in the frequency of good outcome was seen among
      the patients with a history of substance abuse, other psychiatric diagnosis
      (71%), or no psychiatric diagnosis (67%). There was a significant correlation
      between seizure outcome and quality of life score (r(s)=0.67, p<0.001) and
      postoperative employment gains (r(s)=0.48, p=0.01). Outcomes among veterans that
      underwent ATL can be satisfactory even in the context of the late mean age of
      epilepsy onset and the psychiatric diagnoses that were present in this sample.

PMID- 14698708
TI  - Anxiety in children with epilepsy.
AB  - Although the prevalence is unknown, affective disorders are more common in
      children with epilepsy than in healthy controls. The purpose of the present study
      was to examine the occurrence of anxiety in children and adolescents with
      epilepsy and to determine factors associated with elevation of these symptoms.
      Children and adolescents (n=101) between the ages of 6 and 16 years were given
      the Revised Children's Manifest Anxiety Scale (RCMAS). Mild to moderate symptoms
      of anxiety were reported by 23% of the patients. Based on regression analysis,
      factors significantly associated with increased anxiety included the presence of
      comorbid learning or behavioral difficulties, ethnicity, and polytherapy. Results
      suggest the need to monitor children and adolescents with epilepsy for affective
      symptoms in order to provide appropriate interventions.

PMID- 14698710
TI  - A retrospective analysis of the effects of magnet-activated stimulation in
      conjunction with vagus nerve stimulation therapy.
AB  - Vagus nerve stimulation (VNS) therapy offers two methods to help control
      seizures, automatic stimulation delivered at programmed intervals and on-demand
      stimulation initiated with a magnet. This study retrospectively analyzes magnet
      use during the E03 and E04 clinical trials of VNS therapy. Magnet activation that
      aborted, decreased, terminated, or diminished a seizure was classified as an
      improvement; for purposes of evaluation, the patient was considered to have
      received a benefit. When patients in the E03 trial used magnets to activate
      stimulation, patients with active magnets were more likely to report seizure
      improvement than patients with inactive magnets (P=0.0479, Fisher's test). In the
      E04 trial, 22% of patients using the magnet reported seizure termination and 31%
      reported seizure diminution. Unrelated to seizure reduction with programmed VNS
      therapy, approximately half of the patients who used the magnet in this study
      received some benefit. Additional studies can provide a better understanding of
      this unique mode of delivering antiseizure therapy.

PMID- 14698711
TI  - Clinical and neuropsychological characteristics of pediatric epilepsy patients
      with atypical language dominance.
AB  - Studies on intracarotid amobarbital procedures (IAP) in pediatric patients are
      rare and mainly focus on practicability aspects. Very few studies have reported
      characteristics of children with atypical language dominance. We compared
      children with left-sided focal epilepsy and atypical (i.e., right or bilateral)
      versus left-sided language representation (n=12 versus 17). Our results indicate
      a higher incidence of left handedness, extratemporal lesions, an earlier onset of
      epilepsy, and a neuropsychological "crowding effect" with distinct nonverbal
      memory deficits in the atypical group. We conclude that atypical language
      representation in children with left-sided epilepsy is associated with similar
      characteristics as in adults. It is recommended that the possibility of a
      language shift in the presurgical workup of pediatric patients be considered,
      particularly if a left-hemispheric epileptic focus is suspected.

PMID- 14698712
TI  - Frequency of secondary conversion symptoms in children with psychogenic
      nonepileptic seizures.
AB  - We retrospectively identified 22 patients (19 were girls) with psychogenic
      nonepileptic seizures (NES) studied with video EEG telemetry over a 24-month
      period. A history of other conversion symptoms was identified in 11 of 22
      patients. Symptoms were frequently neurological in nature. A strong association
      with depression and history of abuse was noted in children with multiple
      conversion manifestations. These NES patients with secondary conversion symptoms
      may require more intensive psychological therapy and be at risk for long-term
      pathology.

PMID- 14698709
TI  - Comparison between the results of the Symptom Checklist-90 in two different
      populations with temporal lobe epilepsy.
AB  - We performed a prospective psychopathological analysis of two distinct
      populations with temporal lobe epilepsy (TLE), medically treated patients (n=18)
      and patients surgically treated for mesial temporal sclerosis (n=19), and
      compared the psychopathology in the surgical population pre- and postoperatively.
      The Symptom Checklist-90 (SCL-90) was administered to both groups, with the
      surgical patients being tested before and 6 months after surgery. A multivariant
      comparison of the SCL-90 subscales was made between medically treated patients
      and patients before and after surgical treatment. Surgically treated patients had
      less psychopathology after surgery than before. The comparison of surgically
      treated patients with medically treated patients showed statistically significant
      differences in most subscales. Except for the subscale of Hostility, no
      statistically significant differences were found between medically treated
      patients and the surgical population before lobectomy.

PMID- 14698713
TI  - Topiramate and status epilepticus: report of three cases.
AB  - OBJECTIVE: The goal of this study was to report the effectiveness of topiramate
      in treating status epilepticus. METHODS: Three patients with status epilepticus
      were treated with topiramate 500 mg twice daily for 2-5 days, with the dose
      gradually tapered thereafter to 200 mg twice daily. The patients' clinical status
      and EEG recordings were followed. RESULTS: Patient 1 was admitted for subacute
      encephalopathy that was complicated by secondarily generalized status epilepticus
      resistant to lorazepam, fosphenytoin, and pentobarbital coma. Topiramate was
      added and, 2 days later, pentobarbital was tapered with no recurrence of ictal
      discharges as the patient improved clinically. Patient 2 had end-stage liver
      disease and was hospitalized for peritonitis, and his course was complicated by
      partial status epilepticus. Topiramate was started and, 2 days later, his mental
      status improved as repeat EEG showed no further ictal discharges although
      periodic epileptiform discharges were seen in the left centroparietal area. The
      patient later died from complications of variceal bleeding. Patient 3 suffered
      cardiopulmonary arrest, and developed postanoxic seizures, which did not respond
      to lorazepam, fosphenytoin, valproate, and propofol coma as continuous EEG
      recordings showed recurrent generalized ictal discharges. Two days after
      topiramate was started, propofol was tapered and discontinued and EEG showed
      generalized slow wave activity and no ictal discharges. The patient was
      discharged to another facility 12 days later. CONCLUSIONS: Topiramate was
      effective in treating two patients with refractory generalized status epilepticus
      and one with complex partial status epilepticus. It should therefore be
      considered as an option in these situations, especially when other medications
      cannot be used.

PMID- 14698714
TI  - Car drivers with epilepsy (Pilot Hungarian EPIMED Database Evaluation).
AB  - We investigated aspects of driving among Hungarian patients with epilepsy.
      Nineteen percent (148/753) of our population had a driving license (DL),
      including 26% (38/148) who used it. Among persons without a DL, 29% (178/605)
      desired one. Among those who drove (n=38), 24 worked and 8 had experienced
      seizures in the last 3 months. Each of these seizures occurred during sleep
      (5/8), were preceded by known auras and warning signs (2/8) or were provoked by
      extreme external factors (1/8).

PMID- 14698715
TI  - Health care of illegal immigrants post 9-11.

PMID- 14698716
TI  - Adjunctive oxcarbazepine in comorbid anxiety and affective disorder with
      hyponatremic seizure: case analysis and literature review.
AB  - Rational polypharmacy is required for management of refractory psychiatric
      disorders. Antiepileptic drugs are increasingly used as primary or adjunctive
      agents in the treatment of affective, schizoaffective, anxiety, and impulse
      control disorders. In this case report, the authors present the first case of
      hyponatremic seizure associated with oxcarbazepine in adjunctive treatment of
      comorbid affective/anxiety disorders.

PMID- 14698717
TI  - Acute psychosis due to treatment with phenytoin in a nonepileptic patient.
AB  - The development of psychosis related to antiepileptic drug treatment is usually
      attributed to the interaction between the epileptic brain substratum and the
      antiepileptic drugs. The case of a nonepileptic patient who developed psychosis
      following phenytoin treatment for trigeminal neuralgia is described. This case
      suggests that the psychotic symptoms that occur following phenytoin treatment in
      some epileptic patients may be the direct result of medication, unrelated to
      seizures.

PMID- 14698718
TI  - Postictal laughter following absence status epilepticus.
AB  - Acute pathologic neurologic laughter has been described as an ictal phenomenon in
      epilepsy, as a result of electrical brain stimulation to the cortex and to deep
      brain structures, in brain tumors, and in stroke. We report what is, to our
      knowledge, the first report of a case of postictal pathologic laughter.
      Previously diagnosed with medically refractory complex partial seizures, our
      patient was admitted to the hospital with phenytoin toxicity. During video-EEG
      monitoring she experienced multiple brief absence seizures as well as a prolonged
      episode of absence status epilepticus. Immediately following cessation of the
      seizure she began to laugh. Her laughter was mirthful and infectious. This lasted
      several minutes and was followed immediately by several minutes of crying and
      then a return to normal. We propose that diffuse cortical inhibition led to
      release of subcortical structures involved in emotional expression. Possible
      neural substrates of laughter are discussed.

PMID- 14698719
TI  - Functional MRI reveals an interhemispheric dissociation of frontal and temporal
      language regions in a patient with focal epilepsy.
AB  - We report the case of a patient with frontal lobe epilepsy in whom the Wada test
      failed to lateralize representation of language (fluent speech was observed after
      amobarbital injection on both the right and left side). Functional magnetic
      resonance imaging (fMRI) during a lexical processing task revealed an atypical
      organization of language represented by an interhemispheric dissociation of
      language regions with a right frontal dominance and a left temporal dominance.
      Consistent with the fMRI results, the patient's ability to name pictures was not
      reliably impaired by electrocortical stimulation (ECS) of left frontal cortex.
      The findings from Wada, fMRI, and ECS were confirmed by a lack of language
      impairment after left frontal lobectomy for seizures. This case illustrates that
      fMRI can precisely map cortical language networks in epileptic patients and that
      fMRI may be used to help interpret laterality results provided by the Wada
      procedure.

PMID- 14698720
TI  - Resolution of eating disorders after right temporal lesions.
AB  - We report two patients whose eating disorder resolved after right temporal lobe
      lesions. The first case report involves a woman with a history of bulimia nervosa
      and partial seizures arising from the occipital and right temporal regions. The
      second case is a woman with a history of anorexia nervosa that resolved after a
      head injury that resulted in right-sided inferofrontal and temporal
      encephalomalacia. Not only did both patients' eating disorders resolve, but their
      moods and libidos improved.

PMID- 14698721
TI  - Sleep disorders: a sometimes forgotten cause of nonepileptic spells.
AB  - We present a patient with spells of loss of awareness in which the initial
      diagnostic consideration was partial epilepsy. The patient underwent video-EEG
      long-term monitoring which raised suspicion of nonepileptic events, but could not
      exclude simple partial seizures. A failed therapeutic trial with antiepileptic
      medication and adverse events prompted reevaluation of the case. Sleep studies,
      including polysomnography and multiple sleep latency testing (MSLT), confirmed a
      sleep disorder, i.e., narcolepsy, which responded to specific therapy with
      resolution of the spells.

PMID- 14698722
TI  - Rasmussen's syndrome and new-onset narcolepsy, cataplexy, and epilepsy in an
      adult.
AB  - We report a case of new-onset seizures and narcolepsy in a previously healthy 40
      year-old man. He developed severe daytime somnolence and cataplexy over the
      course of a few months. Brain MRI was normal, and polysomnography with multiple
      sleep latency testing confirmed a diagnosis of narcolepsy. His HLA haplotype is
      DQB1*0602 and cerebrospinal fluid analysis showed no detectable hypocretin.
      Approximately 18 months later, he developed complex partial seizures. Further MRI
      showed a progressively enlarging lesion involving the left frontotemporal and
      insular areas. Pathology from a partial resection was consistent with Rasmussen's
      syndrome. Evaluation for tumor, infectious, and paraneoplastic etiologies was
      negative. There was no further progression of the residual lesion on serial MRI.
      Although the pathophysiologic bases of narcolepsy and Rasmussen's syndrome are
      unknown, they may have an autoimmune basis. This unique case of both disorders in
      a single patient suggests the possibility of a common underlying disease process.

PMID- 14698723
TI  - Emperor Napoleon Bonaparte: did he have seizures? Psychogenic or epileptic or
      both?
AB  - Napoleon Bonaparte was a general in the French army at 24 years of age, later
      conquering most of Europe. He was one of the greatest military geniuses the world
      has ever known, but also an extremely intelligent individual. Did he have
      seizures? The evidence shows that he had both psychogenic and epileptic attacks.
      The psychogenic attacks were likely related to the tremendous stress in his life,
      and the epileptic seizures were the result of chronic uremia from a severe
      urethral stricture caused by gonorrhea that was transmitted from his wife,
      Empress Josephine.

PMID- 14698724
TI  - Delineating the functions of the nondominant hemisphere.

PMID- 14698725
TI  - Visual recognition and recall after right temporal-lobe excision in man.
AB  - A further effort was made to determine the effects of right anterior temporal
      lobectomy in man on visual perception and visual memory. Groups of patients with
      cortical resections from right or left temporal, frontal, or parietal regions
      were required to recognize photographs of faces within a larger array, after
      having been shown the faces previously. Three variations of this task were used:
      in the first, the interval between initial presentation and recognition test was
      filled with an irrelevant visual task. In the second, the delay remained but the
      interpolated task was omitted. In the third, there was only minimal delay
      ("immediate recognition"). On the first two tasks, patients with right temporal
      lobe lesions had marked deficits compared with all other groups, but on the third
      task (minimal delay) no clearcut group differences were seen, because the normal
      control group did worse than with delay. Normal subjects (unlike patients with
      right temporal-lobe excisions) apparently use the delay period to consolidate and
      possibly recode their visual impressions. In the context of other tasks sensitive
      to right temporal-lobe lesions, the findings suggest a mild impairment in the
      perception of complex patterns after right anterior temporal lobectomy, and a
      much more severe one in the retention of the perceived material.

PMID- 14698726
TI  - Verb deficits in Alzheimer's disease and agrammatism: implications for lexical
      organization.
AB  - This study examined the nature of verb deficits in 14 individuals with probable
      Alzheimer's Disease (PrAD) and nine with agrammatic aphasia. Production was
      tested, controlling both semantic and syntactic features of verbs, using noun and
      verb naming, sentence completion, and narrative tasks. Noun and verb
      comprehension and a grammaticality judgment task also were administered. Results
      showed that while both PrAD and agrammatic subjects showed impaired verb naming,
      the syntactic features of verbs (i.e., argument structure) influenced agrammatic,
      but not Alzheimer's disease patients' verb production ability. That is,
      agrammatic patients showed progressively greater difficulty with verbs associated
      with more arguments, as has been shown in previous studies (e.g., Kim & Thompson,
      2000; Thompson, 2003; Thompson, Lange, Schneider, & Shapiro, 1997), and suggest a
      syntactic basis for verb production deficits in agrammatism. Conversely, the
      semantic complexity of verbs affected PrAD, but not agrammatic, patients'
      performance, suggesting "bottom-up" breakdown in their verb lexicon, paralleling
      that of nouns, resulting from the degradation or loss of semantic features of
      verbs.

PMID- 14698727
TI  - Effect of intensive training on auditory processing and reading skills.
AB  - This study assessed the ability of seven children to accurately judge relative
      durations of auditory and visual stimuli before and after participation in a
      language remediation program. The goal of the intervention program is to improve
      the children's ability to detect and identify rapidly changing auditory stimuli,
      and thereby improve their language-related skills. Children showed improved
      accuracy on a test of auditory duration judgement following the intervention
      without analogous improvements in the visual domain, supporting the assertion
      that intensive training with modified speech improves auditory temporal
      discrimination. However, these improvements did not generalize to reading skills,
      as assessed by standard measures of phonological awareness and non-word reading.

PMID- 14698728
TI  - Phoneme perception in a neonate with a left sylvian infarct.
AB  - We report the case of a neonate tested three weeks after a neonatal left sylvian
      infarct. We studied her perception of speech and non-speech stimuli with high
      density event-related potentials. The results show that she was able to
      discriminate not only a change of timbre in tones but also a vowel change, and
      even a place of articulation contrast in stop consonants. Moreover, a
      discrimination response to stop consonants was observed even when syllables were
      produced by different speakers. Her intact right hemisphere was thus able to
      extract relevant phonetic information in spite of irrelevant acoustic variation.
      These results suggest that both hemispheres contribute to phoneme perception
      during the first months of life and confirm our previous findings concerning
      bilateral responses in normal infants.

PMID- 14698729
TI  - Electrophysiological evidence of automatic early semantic processing.
AB  - This study investigates the automatic-controlled nature of early semantic
      processing by means of the Recognition Potential (RP), an event-related potential
      response that reflects lexical selection processes. For this purpose tasks
      differing in their processing requirements were used. Half of the participants
      performed a physical task involving a lower-upper case discrimination judgement
      (shallow processing requirements), whereas the other half carried out a semantic
      task, consisting in detecting animal names (deep processing requirements).
      Stimuli were identical in the two tasks. Reaction time measures revealed that the
      physical task was easier to perform than the semantic task. However, RP effects
      elicited by the physical and semantic tasks did not differ in either latency,
      amplitude, or topographic distribution. Thus, the results from the present study
      suggest that early semantic processing is automatically triggered whenever a
      linguistic stimulus enters the language processor.

PMID- 14698730
TI  - Sublexical processing in visual recognition of Chinese characters: evidence from
      repetition blindness for subcharacter components.
AB  - Repetition blindness (RB) refers to the failure to detect the second occurrence
      of a repeated item in rapid serial visual presentation (RSVP). In two experiments
      using RSVP, the ability to report two critical characters was found to be
      impaired when these two characters were identical (Experiment 1) or similar by
      sharing one repeated component (Experiment 2), as opposed to when they were
      different characters with no common components. RB for the whole character
      occurred when the exposure duration was more than 50 ms with one intervening
      character between the two critical characters (lag=1), whereas RB for
      subcharacter components was more evident at exposure durations shorter than 50 ms
      with no intervening character (lag=0). These results provide support for the
      model of sublexical processing in Chinese character recognition.

PMID- 14698731
TI  - Pre-attentive auditory processing of lexicality.
AB  - The effects of lexicality on auditory change detection based on auditory sensory
      memory representations were investigated by presenting oddball sequences of
      repeatedly presented stimuli, while participants ignored the auditory stimuli. In
      a cross-linguistic study of Hungarian and German participants, stimulus sequences
      were composed of words that were language-familiar, lexical, meaningful in
      Hungarian but language-unfamiliar, not lexical, meaningless in German, and words
      with the opposite characteristics. The roles of frequently presented stimuli
      (Standards) and infrequently presented one (Deviants) were fully crossed.
      Language-familiar and language-unfamiliar Deviants elicited the Mismatch
      Negativity component of the event-related brain potential. We found differences
      in processes of change detection depending on whether the Standard was language
      familiar, or not. Whereas, the lexicality of the Deviant had no effect on the
      processes of change detection. Also, language-familiar Standards processed
      differently than language-unfamiliar ones. We suggest that pre-attentive
      (default) tuning to meaningful words sets up language-specific preparatory
      processes that affect change detection in speech sequences.

PMID- 14698732
TI  - Recovery and predictors of language skills two years following pediatric
      traumatic brain injury.
AB  - Subtle language processing difficulties may adversely affect scholastic
      performance, as well as communication and social skills. It is therefore crucial
      that language skills are monitored following traumatic brain injury (TBI) in
      childhood. The present study examined language skills in a group of 68 children
      who had sustained a mild, moderate or severe TBI. Results indicated that during
      the acute stage a dose-response relationship was evident, where severe TBI was
      associated with poorest performance and mild TBI with least deficits. By 24
      months post-TBI, it was clear that for some language functions, the severe TBI
      group showed substantial recovery, and at times performed better than the
      moderate TBI group. Predictors of language and literacy skills at 24 months post
      TBI included pre-injury communication skills, socio-economic status, age at
      injury, and Vocabulary, as measured by the Wechsler Intelligence Scale for
      Children (WISC-111).

PMID- 14698733
TI  - On the prevalence of magnocellular deficits in the visual system of non-dyslexic
      individuals.
AB  - Numerous studies have found visual deficits associated with dyslexia. This has
      made it important to understand how these deficits may be related to reading
      difficulties. A widely held theory is that dyslexia is the result of a deficit in
      the magnocellular part of the visual system (earlier called the transient
      system). In support for this theory, the prevalence of magnocellular deficits has
      been reported to be high among dyslexic readers and very low among non-dyslexic
      ones. This creates the impression that in the population as a whole dyslexic
      individuals have magnocellular deficits and non-dyslexic individuals do not.
      However, we show that because the prevalence of dyslexia itself is low this need
      not be the case. On the basis of previously published data we have estimated the
      number of non-dyslexic and dyslexic individuals with magnocellular deficits. Our
      estimates indicate that there should be a large number of non-dyslexic
      individuals with magnocellular deficits. Paradoxically more individuals without
      dyslexia have magnocellular deficits than individuals with dyslexia. This poses a
      challenge to the view that dyslexia is the result of a magnocellular deficit.

PMID- 14698734
TI  - Linguistic and neuropsychological deficits in crossed conduction aphasia. Report
      of three cases.
AB  - This study describes the linguistic and neuropsychological findings in three
      right-handed patients with crossed conduction aphasia. Despite the location of
      the lesion in the right hemisphere, all patients displayed a combination of
      linguistic deficits typically found in conduction aphasia following analogous
      damage to the left hemisphere. Associated cognitive deficits varied across the
      three patients. In addition, all cases showed deficits classically attributed to
      non-dominant hemisphere damage (visuoperceptual deficits and reduced figural
      memory). As a result, lesion-behaviour relationships in our study sample indicate
      both dominant and non-dominant qualities of the right hemisphere.

PMID- 14698735
TI  - Deficits in thematic integration processes in Broca's and Wernicke's aphasia.
AB  - This study investigated how normal subjects and Broca's and Wernicke's aphasics
      integrate thematic information incrementally using syntax, lexical-semantics, and
      pragmatics in a simple active declarative sentence. Three priming experiments
      were conducted using an auditory lexical decision task in which subjects made a
      lexical decision on a 'target' (the last word of each sentence) preceded by a
      'prime' (a subject noun phrase and verb). The presence and magnitude of priming
      was compared to a baseline condition in which non-words systematically replaced
      real word primes. Normal subjects showed evidence for combinatorial thematics by
      exhibiting significant and larger amounts of thematic priming in the condition
      where two real words were present in the prime than in the conditions in which
      only one real word was present in the prime. Additionally, normal subjects showed
      sensitivity to both syntactic structures and pragmatics. In contrast, Broca's
      patients did not show significant priming for any condition nor did they show a
      difference in the magnitude of priming among the conditions. Nonetheless, they
      showed sensitivity to pragmatics. Wernicke's patients showed significant priming
      for all conditions, but did not show differences in the magnitude of priming
      among the conditions. However, they showed sensitivity to sentence grammaticality
      and pragmatics. The distinct patterns of performance of Broca's and Wernicke's
      aphasics are discussed in terms of the nature of their impairments in the
      processes of combinatorial thematics.

PMID- 14698737
TI  - Reduction of left visual field lexical decision accuracy as a result of
      concurrent nonverbal auditory stimulation.
AB  - To investigate whether concurrent nonverbal sound sequences would affect visual
      hemifield lexical processing, lexical-decision performance of 24 strongly right
      handed students (12 men, 12 women) was measured in three conditions: baseline,
      concurrent neutral sound sequence, and concurrent emotional sound sequence. With
      the neutral sequence, Naveteru, Roy, Ovelac, and Steinling (1992) had observed a
      right greater than left cerebral blood flow, and an opposite pattern with the
      emotional sequence. In the present study, the neutral sound sequence induced a
      significant accuracy reduction for lexical decisions to stimuli presented in the
      left visual field. It is hypothesized that RH activation in response to neutral
      sounds interferes with the limited lexical processing resources of that
      hemisphere.

PMID- 14698736
TI  - The resolution and recovery of filler-gap dependencies in aphasia: evidence from
      on-line anomaly detection.
AB  - This study examines the on-line processing of sentences with movement using an
      auditory anomaly detection task (after Borland, Tanenhaus, Garnsey, & Carlson,
      1995). Eight agrammatic aphasic participants (four of whom had undergone
      treatment focused on comprehension and production of filler-gap sentences) and 24
      young normal participants listened to sentences and pressed a button when the
      sentences "stopped making sense." Critical sentences contained an anomaly in
      object relative clauses or conjoined clauses. Results showed that both young
      normals and aphasic participants were able to reject anomalous sentences of both
      types. In addition, both groups showed evidence of filler-gap resolution on-line.
      Importantly, however, there was evidence of a treatment effect for the aphasic
      patients: those who received treatment showed better performance than those who
      had not. Treated patients were more successful than the untreated patients in
      detecting the anomaly in filler-gap conditions, rejecting the anomalous filler
      gap sentences reliably more often than the non-anomalous ones, like the young
      normals. This effect was not noted for untreated participants, i.e., there was no
      statistical difference between their rejection of anomalous and non-anomalous
      filler gap sentences. Further, the reaction time data showed that the treated
      aphasic patients' rejections came before sentence's end (within 2000 ms), while
      the majority of responses made by untreated patients did not. These results
      indicate that individuals with agrammatic aphasia appear to retain some gap
      filling capacity and that treatment can improve their ability to make use of this
      capacity.

PMID- 14698738
TI  - When is all understood and done? The psychological reality of the recognition
      point.
AB  - Using lexical decision, the effects of primes of different length on spoken word
      recognition were evaluated in three partial repetition priming experiments. Prime
      length was determined via gating (Experiments 1a and 2a). It was shorter than,
      equivalent to, or longer than the recognition point (RP), or a complete word. In
      Experiments 1b and 1c, priming increased with prime length and was independent of
      reaction time. The influence of sensory information following the RP was
      investigated in Experiment 2b. Latencies decreased with increasing prime length,
      but priming decreased only for complete words. RP and complete words have a
      special status. Lexical representations are activated to different degrees at the
      RP and at word offset.

PMID- 14698739
TI  - Syllable frequency and syllable structure in apraxia of speech.
AB  - Recent accounts of the pathomechanism underlying apraxia of speech (AOS) were
      based on the speech production model of Levelt, Roelofs, and Meyer, and Meyer
      (1999)1999. The apraxic impairment was localized to the phonetic encoding level
      where the model postulates a mental store of motor programs for high-frequency
      syllables. Varley and Whiteside (2001a) assumed that in patients with AOS
      syllabic motor programs are no longer accessible and that these patients are
      required to use a subsyllabic encoding route. In this study, we tested this
      hypothesis by exploring the influence of syllable frequency and syllable
      structure on word repetition in 10 patients with AOS. A significant effect of
      syllable frequency on error rates was found. Moreover, apraxic errors on
      consonant clusters were influenced by their position relative to syllable
      boundaries. These results demonstrate that apraxic patients have access to the
      syllabary, but that they fail to retrieve the syllabic motor patterns correctly.
      Our findings are incompatible with a subsyllabic route model of apraxia of
      speech.

PMID- 14698740
TI  - Impact of D1-class dopamine receptor on striatal processing of cortical input in
      experimental parkinsonism in vivo.
AB  - Recent in vivo electrophysiological studies suggest that chronic dopamine
      depletion alters profoundly the firing pattern of basal ganglia neurons. These
      changes may disrupt the processing of cortical information flow from the striatum
      to the output nuclei, and presumably underlie the clinical manifestations of
      Parkinson's disease. We have recently reported that chronic nigrostriatal lesions
      induce changes in the functional state of striatal medium-spiny neurons (MSNs)
      that could facilitate spreading of cortical synchronous activity (approximately 1
      Hz) to striatal target nuclei. Here we show that systemic administration of D1
      dopamine agonists was sufficient to restore the changes induced by chronic
      nigrostriatal lesions on striatal neuronal activity into the normal state.
      Following systemic administration of SKF38393 or SKF81279 the membrane potential
      of striatal MSNs was upheld into a more hyperpolarized value and action potential
      firing probability decreased. D1 agonists also increased the latency to the
      cortically driven plateau depolarization and reduced the peak potential of the
      short latency depolarizing postsynaptic response to a more hyperpolarized value.
      The present study provides in vivo evidence indicating that pharmacological
      stimulation of D1-class dopamine receptors can modulate the flow of cortical
      information through the striatum in the parkinsonian state.

PMID- 14698741
TI  - Neocortical seizures: initiation, development and cessation.
AB  - Different forms of electrical paroxysms in experimental animals mimic the
      patterns of absence seizures associated with spike-wave complexes at
      approximately 3 Hz and of Lennox-Gastaut seizures with spike-wave or polyspike
      wave complexes at approximately 1.5-2.5 Hz, intermingled with fast runs at 10-20
      Hz. Both these types of electrical seizures are preferentially generated during
      slow-wave sleep. Here, we challenge the hypothesis of a subcortical pacemaker
      that would account for suddenly generalized spike-wave seizures as well as the
      idea of an exclusive role of synaptic excitation in the generation of paroxysmal
      depolarizing components, and we focus on three points, based on multiple
      intracellular and field potential recordings in vivo that are corroborated by
      some clinical studies: (a) the role of neocortical bursting neurons, especially
      fast-rhythmic-bursting neurons, and of very fast oscillations (ripples, 80-200
      Hz) in seizure initiation; (b) the cortical origin of both these types of
      electrical paroxysms, the synaptic propagation of seizures from one to other,
      local and distant, cortical sites, finally reaching the thalamus, where the
      synchronous cortical firing excites thalamic reticular inhibitory neurons and
      thus leads to steady hyperpolarization and phasic inhibitory postsynaptic
      potentials in a majority of thalamocortical neurons, which might explain the
      obliteration of signals from the external world and the unconsciousness during
      absence seizures; and (c) the cessation of seizures, whose cellular mechanisms
      have only begun to be investigated and remain an open avenue for research.

PMID- 14698743
TI  - Allopregnanolone and progesterone decrease cell death and cognitive deficits
      after a contusion of the rat pre-frontal cortex.
AB  - We compared the effects of three different doses of allopregnanolone (4, 8 or 16
      mg/kg), a metabolite of progesterone, to progesterone (16 mg/kg) in adult rats
      with controlled cortical impact to the pre-frontal cortex. Injections were given
      1 h, 6 h and every day for 5 consecutive days after the injury. One day after
      injury, both progesterone-treated (16 mg/kg) and allopregnanolone (8 or 16 mg/kg)
      treated rats showed less caspase-3 activity, and rats treated with
      allopregnanolone (16 mg/kg) showed less DNA fragmentation in the lesion area,
      indicating reduced apoptosis. Nineteen days after the injury, rats treated with
      progesterone and allopregnanolone (8 or 16 mg/kg) showed no difference in
      necrotic cavity size but had less cell loss in the medio-dorsal nucleus of the
      thalamus and less learning and memory impairments compared with the injured
      vehicle-treated rats. On that same day the injured rats treated with progesterone
      showed more weight gain compared with the injured rats treated with the vehicle.
      These results can be taken to show that progesterone and allopregnanolone have
      similar neuroprotective effects after traumatic brain injury, but
      allopregnanolone appears to be more potent than progesterone in facilitating CNS
      repair.

PMID- 14698742
TI  - Involvement of peripheral neuropeptide Y receptors in sympathetic modulation of
      acute cutaneous flare induced by intradermal capsaicin.
AB  - In a recent study, we have demonstrated that the dorsal root reflex (DRR)
      mediated acute cutaneous neurogenic inflammation following intradermal injection
      of capsaicin (CAP) is sympathetically dependent and subject to modulation by
      peripheral alpha(1)-adrenoceptors. Postganglionic sympathetic neurons contain not
      only adrenergic neurotransmitters, but also non-adrenergic substances, including
      neuropeptide Y (NPY). In this study, we examined if peripheral NPY receptors
      participate in the flare following CAP injection. Different NPY receptor subtypes
      were studied by using relatively specific agonists and antagonists for the Y(1)
      and Y(2) subtypes. Changes in cutaneous blood flow on the plantar surface of the
      foot were measured using a laser Doppler flowmeter. Following CAP injection,
      cutaneous flare spread more than 20 mm away from the site of CAP injection.
      Removal of the postganglionic sympathetic nerves by surgical sympathectomy
      reduced dramatically the CAP-evoked flare. If the foot of sympathectomized rats
      was pretreated with either NPY or Y(2) receptor agonists by intra-arterial
      injection, the spread of flare induced by CAP injection could be restored and
      prolonged. However, if the spinal cord was pretreated with a GABA(A) receptor
      antagonist, bicuculline, to prevent DRRs, NPY or an Y(2) receptor agonist no
      longer restored the CAP-evoked flare. A Y(1) receptor agonist did not affect the
      CAP-evoked flare in sympathectomized rats. In sympathetically intact rats,
      blockade of either peripheral NPY or Y(2) receptors with [D-Trp(32)]-NPY or
      BIIE0246 markedly reduced the flare induced by CAP injection, whereas blockade of
      peripheral Y(1) receptors by BIBP3226 did not obviously affect the flare. It is
      suggested that NPY is co-released with NE from the postganglionic sympathetic
      terminals to activate NPY Y(2) and alpha(1) receptors following CAP injection.
      Both substances are involved, at least in part, in modulation of the responses of
      CAP sensitive afferents thereby affecting their ability to evoke the release of
      inflammatory agents from primary afferents.

PMID- 14698744
TI  - The diurnal rhythm of adenosine levels in the basal forebrain of young and old
      rats.
AB  - There are significant decrements in sleep with age. These include fragmentation
      of sleep, increased wake time, decrease in the length of sleep bouts, decrease in
      the amplitude of the diurnal rhythm of sleep, decrease in rapid eye movement
      sleep and a profound decrease in electroencephalogram Delta power (0.3-4 Hz). Old
      rats also have less sleep in response to 12 h-prolonged wakefulness (W)
      indicating a reduction in sleep drive with age. The mechanism contributing to the
      decline in sleep with aging is not known but cannot be attributed to loss of
      neurons implicated in sleep since the numbers of neurons in the ventral lateral
      preoptic area, a region implicated in generating sleep, is similar between young
      (3.5 months) and old (21.5 months) rats. One possibility for the reduced sleep
      drive with age is that sleep-wake active neurons may be stimulated less as a
      result of a decline in endogenous sleep factors. Here, we test this hypothesis by
      focusing on the purine, adenosine (AD), one such sleep factor that increases
      after prolonged W. In experiment 1, microdialysis measurements of AD in the basal
      forebrain at 1 h intervals reveal that old (21.5 months) rats have more
      extracellular levels of AD compared with young rats across the 24 h diurnal
      cycle. In experiment 2, old rats kept awake for 6 h (first half of lights-on
      period) accumulated more AD compared with young rats. If old rats have more AD
      then why do they sleep less? To investigate whether changes in sensitivity of the
      AD receptor contribute to the decline in sleep, experiments 3 and 4 determined
      that for the same concentration of AD or the AD receptor 1 agonist,
      cyclohexyladenosine, old rats have less sleep compared with young rats. We
      conclude that even though old rats have more AD, a reduction in the sensitivity
      of the AD receptor to the ligand does not transduce the AD signal at the same
      strength as in young rats and may be a contributing factor to the decline in
      sleep drive in the elderly.

PMID- 14698745
TI  - Expression of c-jun, mitogen-activated protein kinase phosphatase-1, caspase-3
      and glial fibrillary acidic protein following cortical cold injury in rats:
      relationship to metabolic disturbances and delayed cell death.
AB  - The expression of c-jun, mitogen-activated protein kinase phosphatase-1 (mkp-1),
      caspase-3 and glial fibrillary acidic protein (gfap) was examined at 1, 3 and 7
      days after cortical cold injury in rats by in situ hybridisation and
      immunocytochemistry. Alterations of gene expression were related to metabolic
      disturbances and delayed cell death, as revealed by cerebral protein synthesis
      autoradiography, ATP bioluminescence, pH fluorescence and terminal transferase
      biotinylated dUTP nick end labelling (TUNEL). Protein synthesis autoradiographies
      depicted sharply demarcated cortex lesions, which were almost congruent with
      areas exhibiting ATP depletion (lesion volume: 16.9+/-11.8 mm(3) after 7 days).
      Lesions were surrounded by a region of tissue alkalosis, which was most prominent
      1 day after trauma. Delayed cell injury, as revealed by TUNEL, was noticed in a
      thin rim around the lesion border on day 1 (tissue volume: 1.7+/-0.8 mm(3)) and,
      to lesser extent, days 3 and 7 post-lesioning. However, only a small percentage
      of cells in this area were positive for activated caspase-3 protein. TUNEL(+)
      cells were further seen in the ventrobasal thalamus after 7 days. In the
      thalamus, the appearance of DNA-fragmented cells was closely accompanied by
      activated caspase-3 expression. In situ hybridisations revealed that cell injury
      both in the peri-lesion rim and ventrobasal thalamus was associated with
      increased c-jun and gfap, but not mkp-1 and caspase-3 mRNA levels. Gene responses
      were not confined to areas revealing irreversible cell death: mkp-1 mRNA was
      bilaterally upregulated in the lesion-remote entorhinal cortex, cingulate cortex
      and reticular thalamus at 7 days after trauma, and caspase-3 mRNA was slightly,
      but significantly downregulated in the entorhinal cortex after 3 and 7 days. Gfap
      mRNA was elevated in all regions exhibiting tissue alkalosis. Our data suggest
      that delayed cell injury after cortex trauma may be apoptotic in the ventrobasal
      thalamus, but not the peri-lesion rim. The dissociated responses of c-jun, mkp-1
      and caspase-3 mRNAs may represent important factors influencing tissue viability.

PMID- 14698746
TI  - Localization of the KCC4 potassium-chloride cotransporter in the nervous system.
AB  - Potassium-chloride cotransporters (KCCs) collectively play a crucial role in the
      function and development of both the peripheral and central nervous systems. KCC4
      is perhaps the least abundant KCC in the adult mammalian brain, where its
      localization is unknown. In the embryonic brain, KCC4 mRNA is found in the
      periventricular zone, cranial nerves and choroid plexus [Eur J Neurosci 16 (2002)
      2358]. To investigate the distribution of KCC4 protein in the nervous system we
      developed a rabbit polyclonal antibody directed against a short N-terminal
      peptide. Western blot analysis of brain microsomal protein using purified
      antibody revealed the presence of a band at approximately 145 kDa, consistent
      with the size of a glycosylated K-Cl cotransporter. Western blot analysis of
      brain, spinal cord and peripheral nerves revealed high expression levels in
      peripheral nerves and spinal cord, with low levels in whole brain. Within the
      brain, the cerebral cortex, hippocampus, and cerebellum revealed minimal KCC4
      expression, whereas midbrain and brainstem demonstrated higher levels. In the
      adult mouse brain, KCC4 staining was observed on the apical membrane of choroid
      plexus epithelial cells as well as in cranial nerves. All other brain structures,
      e.g. cortex, hippocampus, cerebellum showed no KCC4 immunoreactivity, suggesting
      very low or absent expression of the cotransporter in these regions. Co-staining
      of KCC4 with anti-MAP2, GFAP and CNPase revealed that KCC4 is expressed in
      peripheral neurons. Thus, KCC4 is expressed on the apical membrane of the choroid
      plexus, where it likely participates to K(+) reabsorption. KCC4 is also expressed
      in peripheral neurons, where its function remains to be determined.

PMID- 14698747
TI  - Axotomy dependent purinergic and nitrergic co-expression.
AB  - Different lines of evidence indicate that ATP and nitric oxide (NO) play key
      roles in mediating neuronal responses after cell damage. Purinergic and nitrergic
      interactions have been proposed in non neural tissues physiological functions
      and, in different experimental models of brain injury, both purinergic and
      nitrergic activations have been reported. The present study was planned to
      ascertain possible relations of these two systems after brain damage. Variations
      in the expression of the nitric oxide synthase neuronal isoform (nNOS) enzyme,
      and of two subunits of purinergic ionotrophic receptors (P2X) namely P2X(1) and
      P2X(2) in precerebellar stations after cerebellar lesion in rats were analyzed
      and compared. After the lesion nNOS positive cells presented a clear increment
      followed by a decrement. Conversely, nNOS negative cells presented a rapid
      decrement in the first postlesional weeks that continued less pronounced
      afterward. Postlesional nNOS activation was related with time course of P2X(1)
      and P2X(2) activations. The capacity of the same cells to express both nNOS and
      P2X markers was investigated immunocytochemically. Confocal microscopy of double
      immunofluorescence showed a high percentage of co-localization among P2X(1)/nNOS,
      P2X(2)/nNOS and P2X(1)/P2X(2) in olivary and pontine neurons. In addition,
      NeuN/P2X(1) and NeuN/P2X(2) double immunofluorescence showed P2X(1) expressed
      only in neurons while P2X(2) expressed by both neurons and glia. Present data
      demonstrate that after cerebellar lesion nitrergic and purinergic systems are
      activated with similar time courses in precerebellar stations. Further, time
      differences in the relation between nNOS expression and cell survival suggest a
      multifarious role of NO in mediating cell reaction to axotomy. The tight cellular
      co-localization and temporal co-activation of purinergic and nitrergic markers
      indicate possible interactions between these two systems also in the CNS.

PMID- 14698748
TI  - alpha2a adrenoceptors regulate phosphorylation of microtubule-associated protein
      2 in cultured cortical neurons.
AB  - Adrenoceptors have been suggested to mediate neuronal development. This study
      revealed the expression of alpha2A adrenoceptors in the cortical plate of fetal
      mouse cerebral wall. The effects of alpha2A adrenoceptor on dendrite growth were
      investigated in primary neuronal cultures. Application of alpha2 adrenoceptor
      agonists, BHT 933 or UK 14304 for 24 or 72 h resulted in a 1.5-2-fold increase in
      dendrite lengths. This effect was blocked by alpha2 adrenergic antagonists, RX
      821002 or yohimbine, as well as a alpha2A selective antagonist, BRL 44408, but
      not by alpha2B/alpha2C selective antagonists ARC 239, imiloxan and rauwolscine.
      Guanfacine, a alpha2A selective agonists, also significantly increased the
      dendrite lengths in culture. These results suggest that the morphological effect
      is wholly attributable to alpha2A adrenoceptor activation. We further tested the
      hypothesis that alpha2A adrenoceptors act through altering the phosphorylation
      state of microtubule-associated protein 2. The results showed that the
      phosphorylation of microtubule-associated protein 2 was significantly reduced on
      both serine and threonine residues by over 40% after 2 h of application of
      guanfacine and was maintained at this low level for a prolonged time up to 96 h.
      These findings suggest that alpha2A adrenoceptors regulate the phosphorylation of
      microtubule-associated protein 2, which in turn mediates dendrite growth of
      cortical neurons.

PMID- 14698749
TI  - Neuronal calcium sensor-1 is expressed by dorsal root ganglion cells, is axonally
      transported to central and peripheral terminals, and is concentrated at nodes.
AB  - Neuronal calcium sensor-1 (NCS-1) is a member of the EF-hand calcium-binding
      protein superfamily which has been implicated in the modulation of a number of
      neuronal functions. In this study we have examined the expression of NCS-1 in
      adult rat dorsal root ganglion (DRG) neurons. NCS-1 immunoreactivity was present
      in most DRG neurons, including many calcitonin gene-related peptide (CGRP)
      expressing ones. NCS-1 showed some colocalization with the synaptic vesicle
      protein synaptophysin and underwent both anterograde and retrograde axonal
      transport. NCS-1 immunoreactivity was also present in the dorsal horn of the
      spinal cord, and in peripheral cutaneous terminals innervating blood vessels,
      where it was coexpressed with CGRP. In addition, NCS-1 in peripheral nerves was
      concentrated at nodes and adjoining paranodes. These results suggest novel roles
      for NCS-1, particularly in relation to channel function at nodes and to the
      peripheral release of vasoactive peptides.

PMID- 14698750
TI  - Exercise reverses the harmful effects of consumption of a high-fat diet on
      synaptic and behavioral plasticity associated to the action of brain-derived
      neurotrophic factor.
AB  - A diet high in total fat (HF) reduces hippocampal levels of brain-derived
      neurotrophic factor (BDNF), a crucial modulator of synaptic plasticity, and a
      predictor of learning efficacy. We have evaluated the capacity of voluntary
      exercise to interact with the effects of diet at the molecular level. Animal
      groups were exposed to the HF diet for 2 months with and without access to
      voluntary wheel running. Exercise reversed the decrease in BDNF and its
      downstream effectors on plasticity such as synapsin I, a molecule with a key role
      in the modulation of neurotransmitter release by BDNF, and the transcription
      factor cyclic AMP response element binding protein (CREB), important for learning
      and memory. Furthermore, we found that exercise influenced the activational state
      of synapsin as well as of CREB, by increasing the phosphorylation of these
      molecules. In addition, exercise prevented the deficit in spatial learning
      induced by the diet, tested in the Morris water maze. Furthermore, levels of
      reactive oxygen species increased by the effects of the diet were decreased by
      exercise. Results indicate that exercise interacts with the same molecular
      systems disrupted by the HF diet, reversing their effects on neural function.
      Reactive oxygen species, and BDNF in conjunction with its downstream effectors on
      synaptic and neuronal plasticity, are common molecular targets for the action of
      the diet and exercise. Results unveil a possible molecular mechanism by which
      lifestyle factors can interact at a molecular level, and provide information for
      potential therapeutic applications to decrease the risk imposed by certain
      lifestyles.

PMID- 14698751
TI  - Excitotoxic insults to the optic nerve alter visual evoked potentials.
AB  - Excitotoxic oligodendroglial death is one of the mechanisms which has been
      proposed to underlie demyelinating diseases of the CNS. We describe here
      functional consequences of excitotoxic lesions to the rabbit optic nerve by
      studying the visual evoked potentials (VEPs) measured in the visual cortex.
      Nerves were slowly infused with the excitotoxin kainate a subcutaneously
      implanted osmotic pump which delivered the toxin through a cannula onto the optic
      nerve. Records of VEPs were obtained before pump implantation and at 1, 3 and 7
      days post-implantation, and weekly evaluated thereafter for up to 4 months. We
      observed that the VEPs generated by light stimuli progressively changed in both
      amplitude and profile after the lesion as well as in comparison to those
      generated in control animals infused with vehicle. Histological examination of
      the damage caused by the excitotoxic insult showed that large areas of the optic
      nerve were demyelinated and their axons distorted. These observations were
      confirmed and extended by immunohistochemical analyses using markers to
      neurofilaments, myelin basic protein and the oligodendrocyte marker APC. The
      results of the present paper indicate that the consequences of excitotoxicity in
      the optic nerve share functional and morphological alterations which are found in
      demyelinating disorders. In addition, this experimental paradigm may be useful to
      evaluate the functional recovery of demyelinated optic nerves following various
      repair strategies.

PMID- 14698752
TI  - Disinhibition of ventrolateral preoptic area sleep-active neurons by adenosine: a
      new mechanism for sleep promotion.
AB  - The ventrolateral preoptic area of the hypothalamus (VLPO) contains a population
      of sleep-active neurons and is hypothesized to be an important part of the
      somnogenic process. Adenosine (AD) is an endogenous sleep-promoting factor and
      may play an important role in promoting natural sleep. We hypothesize that AD may
      promote sleep, in part, by activating the VLPO sleep-active neurons. Although, in
      the CNS, AD is generally regarded as an inhibitory neuromodulator, it is possible
      for AD to be directly excitatory via A2 receptors or indirectly via
      disinhibition. In order to test the hypotheses that AD can excite VLPO neurons we
      made intracellular recordings from the VLPO in vitro and examined the effects of
      AD on VLPO neural activity. Whole cell patch-clamp recordings were obtained from
      rat brain slices and drugs were bath applied. VLPO neurons were
      electrophysiologically heterogeneous. Depolarizing current steps elicited
      rhythmic firing (25 of 57), spike frequency adaptation or accommodation (24 of
      57), or an unusual burst firing response (eight of 57). Spontaneous synaptic
      activity was pronounced in most recorded neurons and consisted of either fast
      excitatory post-synaptic potentials/currents (EPSP/C's) and/or fast inhibitory
      post-synaptic potentials/currents (IPSP/C's). The IPSC's were fully blocked by 30
      microM bicuculline suggesting they are GABA(A)-mediated events, and the EPSC's
      were blocked by 40 microM DNQX suggesting they are mediated by the AMPA subtype
      of glutamate receptor (five of five). AD (20-100 microM) reduced the frequency of
      spontaneous IPSC's in 11 of 17 VLPO neurons (28-100%; mean reduction=63%) without
      significant effects on resting membrane potential. IPSC was unaffected in five
      neurons and one neuron displayed increases in spontaneous IPSC's. In contrast, AD
      decreased EPSC frequency in seven cells (36-73%; mean=59%), increased frequency
      in five cells (30-236%; mean 83%) and had no effect in six cells. AD application
      increased the firing rate in two of four cells tested. These data are consistent
      with the hypothesis that one mechanism which AD may promote sleep is by blocking
      inhibitory inputs on VLPO sleep-active neurons.

PMID- 14698753
TI  - Over-expression of parvalbumin in transgenic mice rescues motoneurons from injury
      induced cell death.
AB  - Following nerve injury in neonatal rats, a large proportion of motoneurons die,
      possibly as a consequence of an increase in vulnerability to the excitotoxic
      effects of glutamate. Calcium-dependent glutamate excitotoxicity is thought to
      play a significant role not only in injury-induced motoneuron death, but also in
      motoneuron degeneration in diseases such as amyotrophic lateral sclerosis (ALS).
      Motoneurons are particularly vulnerable to calcium influx following glutamate
      receptor activation, as they lack a number of calcium binding proteins, such as
      calbindin-D(28k) and parvalbumin. Therefore, it is possible that increasing the
      ability of motoneurons to buffer intracellular calcium may protect them from cell
      death and prevent the decline in motor function that usually occurs as a
      consequence of motoneuron loss. In this study we have tested this possibility by
      examining the effect of neonatal axotomy on motoneuron survival and muscle force
      production in normal and transgenic mice that over-express parvalbumin in their
      motoneurons.The sciatic nerve was crushed in one hindlimb of new-born transgenic
      and wildtype mice. The effect on motoneuron survival was assessed 8 weeks later
      by retrograde labelling of motoneurons innervating the tibialis anterior muscle.
      Following nerve injury in wildtype mice, only 20.2% (+/-2.2, S.E.M.; n=4) of
      injured motoneurons survive long term compared with 47.2% (+/-4.4, S.E.M.; n=4)
      in parvalbumin over-expressing mice. Surprisingly, this dramatic increase in
      motoneuron survival was not reflected in a significant improvement in muscle
      function, since 8 weeks after injury there was no improvement in either maximal
      twitch and tetanic force, or muscle weights.Thus, inducing spinal motoneurons to
      express parvalbumin protects a large proportion of motoneurons from injury
      induced cell death, but this is not sufficient to restore muscle function.

PMID- 14698754
TI  - Development and aging of N-methyl-D-aspartate receptor expression in the
      prefrontal/frontal cortex of mice.
AB  - The present study was designed to determine whether the changes that occur during
      aging in the expression of the N-methyl-D-aspartate (NMDA) receptor and two NMDA
      receptor subunits, zeta1 and epsilon2, are a continuation of developmental
      processes and whether protein and mRNA expression patterns of the subunits are
      similar across the lifespan. The prefrontal/frontal cortex of C57BL/6 mice of
      eight different ages (7-8, 13-15, 30-32, 49-53, and 70-72 days and 4.5, 11, and
      25 months of age) were used to examine NMDA-displaceable [(3)H]glutamate binding
      and mRNA in tissue sections and mRNA and protein from homogenates. The lateral
      prefrontal/frontal cortex of C57BL/6 mice showed more significant declines in
      density of agonist binding to NMDA receptors during both development and aging
      than the medial cortex. Changes in mRNA expression for the epsilon2 subunit
      across the lifespan appeared to be related to the changes in NMDA receptor
      binding in the lateral cortex, even though the protein expression of the epsilon2
      subunit did not show the same pattern of expression as the mRNA during
      development. The changes in epsilon2 subunit mRNA expression during adult aging
      may be a continuation of developmental processes, but there was also evidence
      that expression levels plateaued during early adulthood. The developmental
      expression of the zeta1subunit in the prefrontal/frontal cortex was influenced by
      gender and there was no significant effect of adult aging on either the protein
      or mRNA expression of this subunit. Determining how the expression of the NMDA
      receptor and its subunits change throughout the lifespan can help us to better
      understand the processes affecting the receptor during aging. These results
      should be useful for designing interventions into the aging process to repair or
      prevent changes in the NMDA receptor and its associated functions, such as
      learning and memory.

PMID- 14698755
TI  - Prenatal cocaine exposure alters potassium-evoked dopamine release dynamics in
      rat striatum.
AB  - The emerging profile for the effects of prenatal cocaine exposure presents two
      prominent features in the exposed offspring: cognitive/attention deficits and an
      age-associated trend toward motor/tone abnormalities up to 2 years of age. One
      candidate mechanism underlying these clinical features is long-lasting
      alterations to dopamine (DA) neuron function. However, the impact of prenatal
      cocaine exposure on DA release in dopaminergic terminal fields in vivo in mature
      offspring is poorly understood. Long-Evans female rats were implanted with an
      i.v. access port, bred, and given saline or cocaine-HCl (3 mg/kg/ml) for
      gestational days (GD) 8-14 (1x/day), GD 15-21 (2x/day), or GD 8-21 (1x/day-GD 8
      14, 2x/day-GD 15-21). Using in vivo high-speed chronoamperometric recordings,
      potassium-stimulated DA release was measured in striatum of anesthetized male
      offspring 90-150 days after birth. There was a trend toward increased potassium
      evoked DA signal amplitudes in offspring exposed to cocaine at any time period
      examined. In offspring exposed to cocaine during GD 8-21 and GD 15-21, but not at
      GD 8-14, there were significant decreases in the clearance capacity of the
      potassium-evoked DA signal compared with control offspring. The time required to
      clear 80% of the evoked DA signal (T(80)) in striatum for DA was significantly
      prolonged (approximately 150% of control) and this effect was further increased
      in the mean-evoked DA concentration range for these two groups. We also measured
      total dopamine transporter (DAT) and tyrosine hydroxylase protein levels in these
      offspring by blot immunolabeling and found a small, but significant, decrease in
      DAT protein in striatum from offspring exposed at GD 8-21 and GD 15-21.
      Collectively, these data demonstrate that prenatal cocaine exposure during
      dopamine neuron neurogenesis has long-lasting effects on DA neuron function
      lasting into early adulthood which may be related in part to steady state DAT
      protein levels. These molecular events may be associated with established
      cognitive deficits and perhaps the trends seen in altered motor behavior.

PMID- 14698756
TI  - Activaton of GABAB receptor inhibits the excitability of rat small diameter
      trigeminal root ganglion neurons.
AB  - A selective GABA(B) receptor agonist, baclofen, is known to suppress neuropathic
      pain. In the present study, we investigated the effect of baclofen on the
      excitability of trigeminal root ganglion (TRG) neurons by using the whole cell
      and perforated patch-clamp recording techniques. Under voltage-clamp (V(h)=-60
      mV), voltage-dependent K(+) currents were recorded in the small diameter TRG
      neurons (<30 microm) and isolated by blocking Na(+) and Ca(2+) currents with
      appropriate ion replacement. Separation of the K(+) current components was
      achieved by the response to variation in the conditioning voltage. Two distinct
      K(+) current components, a transient (I(A)) and a sustained (I(k)), were
      identified. Baclofen significantly increased I(A) by 74.8% (50 microM) and in a
      dose-dependent manner (1-50 microM). Similarly, I(K) was also enhanced by
      baclofen administration (41.8%: 50 microM). The relative amplitude of
      potentiation of I(A) was significantly higher than that of I(K) (P<0.05).
      Baclofen-sensitive I(A) and I(K) currents were antagonized by K(+) channel
      blockers, 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The augmentation
      of K(+) currents was antagonized by 3-amino-2-(4-chlorophenyl)-2
      hydroxypropylsulfonic acid (saclofen; GABA(B) antagonist). In the current clamp
      mode, the resting membrane potential was -62+/-1.6 mV (n=24). Hyperpolarization
      of the membrane potential was elicited by baclofen (10-50 microM), and the
      response was associated with a decrease in the input resistance. Baclofen induced
      hyperpolarization was blocked by saclofen (100 microM). In the presence of both 4
      AP and TEA, no significant changes in membrane potential induced by baclofen
      application were observed. In the presence of BaCl(2), baclofen-evoked
      hyperpolarization with decreased resistance was observed. During application of
      baclofen, the firing rate of the action potentials by depolarizing step pulses
      was decreased. Application of baclofen reduced action potential duration evoked
      by a depolarization current pulse.These results indicated that activation of
      GABA(B) receptors inhibits the excitability of rat small diameter TRG neurons and
      this inhibitory action is mediated by potentiation of voltage-dependent K(+)
      currents. We therefore concluded that modification of nociceptive transmission in
      the trigeminal system by activation of GABA(B) receptors occurs at the level of
      small TRG neuron cell bodies and/or their primary afferent terminals, which are
      potential targets of analgesia by baclofen.

PMID- 14698757
TI  - Synaptically stimulated induction of group I metabotropic glutamate receptor
      dependent long-term depression and depotentiation is inhibited by prior
      activation of metabotropic glutamate receptors and protein kinase C.
AB  - We have investigated metaplasticity of the group I metabotropic glutamate
      receptor (mGluR)-dependent long-term depression (LTD) and depotentiation (DP)
      induced by physiological synaptic stimulation in the medial perforant path of the
      dentate gyrus in vitro. Group I mGluR-LTD/DP was inhibited by prior
      preconditioning brief high frequency stimulation (HFS) if the preconditioning HFS
      induced long-term potentiation (LTP) or if the induction of LTP was inhibited by
      an NMDA receptor antagonist. The inhibitory effect of the preconditioning HFS on
      LTD/DP was dependent upon activation of mGluRs, as it was blocked by the presence
      of the mGluR antagonist (S)-alpha-methyl-4-carboxyphenylglycine during the
      preconditioning stimulation. The inhibitory effect of the preconditioning HFS
      involved stimulation of PKC, as the presence of the PKC inhibitor
      bisindolylmaleimide (BIS) during the preconditioning stimulation prevented the
      inhibitory effect of such preconditioning stimulation. Activation of PKC was also
      necessary for the induction of mGluR-LTD itself, as the PKC inhibitor BIS
      prevented the induction of the mGluR-LTD. We suggest that the physiological
      stimulation of mGluRs by the preconditioning stimulation produces a PKC-dependent
      inactivation of subsequent group I mGluR functioning and thereby an inhibition of
      induction of group I mGluR-dependent LTD/DP induction.

PMID- 14698758
TI  - Effects of estrone on N-methyl-D-aspartic acid- and staurosporine-induced changes
      in caspase-3-like protease activity and lactate dehydrogenase-release: time- and
      tissue-dependent effects in neuronal primary cultures.
AB  - A growing body of evidence indicates that estrogens affect apoptotic processes in
      neuronal cells. However, their effects seem to depend on type of neuronal tissue,
      stage of development and apoptosis inducing factors. In the present study we
      compared effects of estrone (100 and 500 nM) on N-methyl-D-aspartic acid (NMDA)
      (1 mM)- and staurosporine (1 microM)-induced caspase-3-like activity and lactate
      dehydrogenase (LDH)-release in primary cultures of rat hippocampal and
      neocortical neurons. Fluorometric and colorimetric determination of enzyme
      activity was performed 6 h, 14 h, and 24 h after exposure to apoptotic agents. In
      the hippocampal cell cultures on 7 days in vitro (DIV), a time-dependent NMDA
      induced activation of caspase-3-like proteases was accompanied by increased LDH
      release. In neocortical cell cultures on 7 DIV NMDA did not affect caspase
      activity and decreased LDH-release. In neocortical cell cultures on 12 DIV NMDA
      inhibited spontaneous caspase activity, but was toxic to neurons after 24 h
      exposure suggesting that these cells underwent necrotic rather than apoptotic
      death. Estrone has attenuated both pro- and anti-apoptotic NMDA-induced changes
      in rat primary neuronal cultures acting independently of estrogen receptors, as
      detected with ICI 182, 780. In hippocampal neurons estrone antagonized not only
      the NMDA-induced caspase-3-like activity, but also NMDA-mediated LDH-release.
      However, in neocortical neurons estrone either attenuated NMDA-induced inhibition
      of caspase-3-like activity (12 DIV) or partly blocked NMDA-mediated decrease in
      LDH-release (7 DIV). In contrast to NMDA, staurosporine elevated caspase-3-like
      activity and LDH-release in a time-dependent manner in all used culture systems.
      Estrone inhibited pro-apoptotic effects of staurosporine in neocortical neurons,
      but only at later stage of development in vitro, which points to the protective
      role of estrogens during the brain tissue maturation. Since estrone triggered its
      effects via non-genomic mechanisms, it suggests that the other estradiol
      metabolites exhibiting low affinity to hormone receptors may be potent
      neuroprotective agents, which could retain the favorable and minimize the adverse
      side effects of estrogens.

PMID- 14698759
TI  - The involvement of the blood-brain and the blood-cerebrospinal fluid barriers in
      the distribution of leptin into and out of the rat brain.
AB  - Leptin is a 16 kDa hormone that is produced by adipose tissue and has a central
      effect on food intake and energy homeostasis. The ability of leptin to cross the
      blood-brain and blood-cerebrospinal fluid (CSF) barriers and reach or leave the
      CNS was studied by the bilateral in situ brain perfusion and isolated incubated
      choroid plexus techniques in the rat. Brain perfusion results indicated that
      [(125)I]leptin reached the CNS at higher concentrations than the vascular marker,
      confirming that [(125)I]leptin crossed the brain barriers. Leptin distribution
      varied between CNS regions and indicated that the blood-brain barrier, in
      contrast to the blood-CSF route, was the key pathway for [(125)I]leptin to reach
      the brain. Further perfusion studies revealed that [(125)I]leptin movement into
      the arcuate nucleus, thalamus, frontal cortex, choroid plexuses and CSF was
      unaffected by unlabelled human or murine leptin at a concentration that reflects
      the upper human and rat plasma leptin concentration (2.5 nM). In contrast, the
      cerebellum uptake of [(125)I]leptin was decreased by 73% with 2.5 nM human
      leptin. Thus, this site of dense leptin receptor expression would be sensitive to
      physiological changes in leptin plasma concentrations. The highest rate (K(in))
      of [(125)I]leptin uptake was into the choroid plexuses (307.7+/-68.0
      microl/min/g); however, this was not reflected in the CSF (8.9+/-4.1
      microl/min/g) and indicates that this tissue tightly regulates leptin
      distribution. The multiple-time brain uptake of [(125)I]leptin was non-linear and
      suggested leptin could also be removed from the CNS. Studies using the incubated
      rat choroid plexus model found that [(125)I]leptin could cross the apical
      membrane of the choroid plexus to leave the CSF. However, this movement was not
      sensitive to unlabelled human leptin or specific transport inhibitors/modulators
      (including probenecid, digoxin, deltorphin II, progesterone and
      indomethacin).This study supports the concept of brain-barrier regulation of
      leptin distribution to the CNS, and highlights an important link between leptin
      and the cerebellum.

PMID- 14698760
TI  - Altered neurotensin mrna expression in mice lacking the dopamine transporter.
AB  - Psychostimulants and antipsychotic drugs increase mRNA expression of the
      neuropeptide neurotensin (NT) in the striatum and nucleus accumbens. In the
      present study, we used mice lacking the dopamine transporter (DAT) to investigate
      the consequences of a chronic hyperdopaminergic state on NT gene expression. NT
      mRNA expression was examined under basal conditions and after administration of
      haloperidol or amphetamine using in situ hybridization with a digoxigenin-labeled
      NT cRNA probe. DAT-/- mice exhibited a striking increase in the number of NT mRNA
      expressing perikarya in the substantia nigra and ventral tegmental area, as well
      as a less pronounced increase in the lateral septum compared with wild-type
      littermates. No changes were detected in other regions expressing NT mRNA. Acute
      administration of haloperidol (1 mg/kg) induced a significant increase in the
      number of NT mRNA-expressing neurons in the dorsomedial and dorsolateral striatum
      of wild-type mice but failed to stimulate NT gene expression in DAT mutants. In
      contrast, a higher dose of haloperidol (5 mg/kg) stimulated striatal NT mRNA
      expression both in DAT+/+ and DAT-/- mice. Amphetamine (10 mg/kg) increased the
      number of hybridized neurons in the nucleus accumbens shell and fundus striati of
      wild-type and DAT-/- mice, indicating that the drug acted through a target other
      than DAT, such as the serotonin or the norepinephrine transporters. The up
      regulation of NT mRNA observed in DAT-/- mice may represent an adaptive mechanism
      in response to constitutive hyperdopaminergia. These results illustrate the
      profound alterations in the NT system induced by chronic stimulation of DA
      receptors and underscore the potential clinical relevance of NT/DA interactions
      in schizophrenia and drug abuse.

PMID- 14698761
TI  - Perisomatic glutamatergic axon terminals: a novel feature of cortical synaptology
      revealed by vesicular glutamate transporter 1 immunostaining.
AB  - The cellular localization of the vesicular glutamate transporter 1, VGLUT1, was
      studied in the rat cerebral cortex with immunocytochemical techniques. VGLUT1
      immunoreactivity (ir) was localized to punctate structures dispersed in the
      neuropil of all cortical layers as well as around the profile of somata and
      proximal dendritic segments of virtually all pyramidal neurons. Using a
      correlative light and electron microscopic method, we found that VGLUT1 ir is
      expressed in axon terminals forming synapses exclusively with dendritic shafts
      and spines. Perisomatic VGLUT1-positive terminals never formed synapses with the
      pyramidal cell bodies to which they were in apposition, but formed asymmetric
      synapses with adjacent neuropilar dendritic elements. The high probability of a
      close spatial relationship between glutamatergic and GABAergic terminals in
      perisomatic regions suggests that spilled-out glutamate may act on inhibitory
      axon terminals innervating the soma of cortical pyramidal neurons.

PMID- 14698762
TI  - Glutamic acid decarboxylase immunoreactivity in callosal projecting neurons of
      cat and rat somatic sensory areas.
AB  - The distribution of GABAergic callosally projecting neurons was analysed in the
      somatic sensory areas of cat and rat cerebral cortex by combining retrograde
      tracing of nerve cell bodies and glutamic acid decarboxylase (GAD)
      immunocytochemistry. A retrograde tracer (colloidal gold- labelled wheat germ
      agglutinin conjugated to enzymatically inactive horseradish peroxidase) was
      injected in the first or second somatic sensory area. Brain sections were
      processed for the simultaneous visualisation of the retrograde tracer and GAD
      immunoreactivity. In all animals, double-labelled neurons were found in the
      hemisphere contralateral to the injection site (double-labelled callosal
      neurons). Their proportion was similar in both species (0.8% of all retrogradely
      labelled neurons in cat, 0.7% in rat). These results: 1) confirm the existence of
      a small proportion of GABAergic callosally projecting neurons in rat somatic
      sensory cortices; 2) indicate the presence of a small but significant proportion
      of GAD-positive callosally projecting neurons in cat somatic sensory cortices;
      and 3) show that the proportion of GAD-positive callosal neurons is similar in
      the two species.

PMID- 14698763
TI  - Cortical spreading depression blocks the hyperthermic reaction induced by orexin
      A.
AB  - This experiment tested the effect of cortical spreading depression on the
      sympathetic and thermogenic effects induced by orexin A. The firing rates of the
      sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT
      and colonic temperatures and heart rate were monitored in urethane-anesthetized
      male Sprague-Dawley rats before and 5 h after an injection of orexin A (1.5 nmol)
      into the lateral cerebral ventricle. The same variables were monitored in rats
      with cortical spreading depression, induced by an application of cotton pellets
      soaked with 2 M KCl to the frontal cortex. The results show that orexin A
      increases the sympathetic firing rate, IBAT and colonic temperatures and heart
      rate. The increases in firing rate, IBAT and colonic temperatures are blocked by
      cortical spreading depression, while the increase in heart rate is not affected
      by cortical spreading depression. These findings suggest that the cerebral cortex
      is involved in the control of the orexin A-induced hyperthermia. Furthermore, we
      suggested the name "hyperthermine A," as additional denomination of "orexin A."

PMID- 14698764
TI  - Hypothalamic contribution to sleep-wake cycle development.
AB  - Infant mammals cycle rapidly between sleep and wakefulness and only gradually
      does a more consolidated sleep pattern develop. The neural substrates responsible
      for this consolidation are unknown. To establish a reliable measure of sleep-wake
      cyclicity in infant rats, nuchal muscle tone was measured in 2-, 5-, and 8-day
      old rats, as were motor behaviors associated with sleep (i.e. myoclonic
      twitching) and wakefulness (e.g. kicking, stretching). Sleep-wake cycles of 2-day
      old rats were characterized by short periods of muscle atonia followed by equally
      short periods of high tone. In 8-day-olds, sleep periods lengthened significantly
      and disproportionately in relation to awake periods. Next, locus coeruleus (LC)
      lesions in 8-day-olds resulted in rapid sleep-wake cycling similar to that
      exhibited by 2-day-olds; in addition, LC lesions had no effect on the duration of
      awake periods. Finally, transections caudal, but not rostral, to the anterior
      hypothalamus also reinstated rapid cycling in 8-day-olds, again without affecting
      the duration of awake periods. This last finding implicates neural structures
      within the anterior hypothalamus (e.g. ventrolateral preoptic area) in the
      modulation of sleep-wake cyclicity. The temporal coherence of atonia and
      myoclonic twitching was not disrupted by any of the manipulations. These results
      suggest the presence of a bistable mesopontine circuit governing rapid sleep-wake
      cycling that does not include the LC and that comes increasingly under
      hypothalamic control during the first postnatal week. This circuit may represent
      a basic building block with which other sleep components become integrated during
      ontogeny.

PMID- 14698765
TI  - Loading and recycling of synaptic vesicles in the Torpedo electric organ and the
      vertebrate neuromuscular junction.
AB  - In vertebrate motor nerve terminals and in the electromotor nerve terminals of
      Torpedo there are two major pools of synaptic vesicles: readily releasable and
      reserve. The electromotor terminals differ in that the reserve vesicles are twice
      the diameter of the readily releasable vesicles. The vesicles contain high
      concentrations of ACh and ATP. Part of the ACh is brought into the vesicle by the
      vesicular ACh transporter, VAChT, which exchanges two protons for each ACh, but a
      fraction of the ACh seems to be accumulated by different, unexplored mechanisms.
      Most of the vesicles in the terminals do not exchange ACh or ATP with the
      axoplasm, although ACh and ATP are free in the vesicle interior. The VAChT is
      controlled by a multifaceted regulatory complex, which includes the proteoglycans
      that characterize the cholinergic vesicles. The drug (-)-vesamicol binds to a
      site on the complex and blocks ACh exchange. Only 10-20% of the vesicles are in
      the readily releasable pool, which therefore is turned over fairly rapidly by
      spontaneous quantal release. The turnover can be followed by the incorporation of
      false transmitters into the recycling vesicles, and by the rate of uptake of FM
      dyes, which have some selectivity for the two recycling pathways. The amount of
      ACh loaded into recycling vesicles in the readily releasable pool decreases
      during stimulation. The ACh content of the vesicles can be varied over eight-fold
      range without changing vesicle size.

PMID- 14698766
TI  - Paying attention to consciousness.
AB  - An engineering control approach is developed for the movement of attention, based
      on several features: experimental data indicating separate sites for attention
      modulation and for the creation of that modulation; the resulting analogy with
      motor control, to which an engineering approach has been applied; simulation and
      qualitative results supporting the presence of several of the necessary modules.
      These features are reviewed in the paper and a control model developed for the
      movement of attention. The engineering control framework is extended to the
      attended learning of motor control, again with description of support arising
      from simulations and qualitative analysis of several paradigms. The framework is
      even further extended to analyze how consciousness could arise during attentive
      processing, using the COrollary Discharge of Attention Movement (CODAM) model.
      This model is extended to encompass the temporal development of activity in
      various brain sites. Particular signals of the CODAM model are described and
      related to paradigms such as the attentional blink (AB) and features of
      simultaneous experience in neglect. A program of future explorations of the CODAM
      model and a set of open questions conclude the paper.

PMID- 14698768
TI  - Marginal and flexural integrity of three classes of luting cement, with early
      finishing and water storage.
AB  - OBJECTIVES: The aims of this investigation were to clarify the effects of
      finishing-time and 24 h water-storage on mechanical properties and marginal
      adaptation to dentin of seven modern luting cements, representing three chemical
      types. METHODS: Bistite II, Chemiace II, Compolute, XenoCem, PermaCem, Fuji Cem
      and Fuji Plus were investigated with specimen sub-groups (N=10) for each property
      measured. The principal series of experiments was conducted in dentin cavities
      with interfacial polishing either immediately (3 min) after setting or after 24 h
      water-storage. After the finishing procedure, the maximum marginal gap width and
      the opposing width (if any) per cavity were measured microscopically, and summed.
      Then the overall sum of gap-widths (per group; N=10) was calculated. Marginal
      gaps were similarly measured in Teflon cavities, together with shear-bond
      strengths to dentin and early flexural strengths, moduli and swelling data.
      RESULTS: For specimen-sets polished immediately after setting, summed marginal
      gaps of 23-121 microm were observed, for all luting cements except Compolute. A
      significantly different (p<0.05) result of either no gap or 6-28 microm summed
      gap-widths occurred in specimens polished after 24 h. For all materials, their
      shear-bond-strengths, flexural strength and moduli significantly increased after
      24 h storage. SIGNIFICANCE: The marginal behavior can be interpreted in terms of
      the contributions of bonding, shrinkage, swelling and compliance of components,
      along with compositional features of the cements. With these types of cement it
      is generally inadvisable to polish the interfacial luting surface immediately
      after cementing. The polishing procedures should be carried out not less than 24
      h later. One resin-cement was able to withstand immediate finishing.

PMID- 14698769
TI  - Resin composite monomers alter MTT and LDH activity of human gingival fibroblasts
      in vitro.
AB  - OBJECTIVES: Substances such as monomers may be released from composite resin
      systems and may induce adverse effects in biological tissues. The aim of this
      study is to investigate the cytotoxic concentrations of resin composite monomers
      on cultures of human gingival fibroblasts. METHODS: A range of dilutions of five
      resin composite monomers (HEMA, HPMA, DMAEMA, TEGDMA, and Bis-GMA) were added to
      the culture medium of human gingival fibroblasts for 24 h. Their cytotoxic
      effects were measured by using two colorimetric functional assays, mitochondrial
      dehydrogenase activity (MTT) and lactate dehydrogenase activity (LDH) assay. The
      logP values (water/octanol partition) of test monomers were also calculated
      computationally. RESULTS: Mitochondrial reducing activity assessed with the MTT
      test was inhibited by all monomers and all the monomers increased the LDH release
      in a reproducible dose dependent manner. A wide range of TC 50 values
      (concentrations altering MTT and LDH activity by 50%) (0.32-5.8 mM by MTT assay
      and 0.36-6.7 mM by LDH assay) was observed. Ranking of composite resin monomer
      cytotoxicities (TC 50) were similar for both the MTT and LDH assays, (Bis
      GMA>TEGDMA>DMAEMA>HPMA >HEMA). However, the MTT assay was found to be more
      sensitive than the LDH assay, particularly when lower doses of the tested
      monomers were determined. The ranking of TC 50 concentrations correlated with the
      calculated logP values. SIGNIFICANCE: Monomers used in dental restorative
      materials show a variety of toxic effects on gingival fibroblasts. A combination
      approach using MTT and LDH assays provides valuable information about their toxic
      effects.

PMID- 14698771
TI  - Flexural properties of fiber reinforced root canal posts.
AB  - OBJECTIVES: Fiber-reinforced composite (FRC) root canal posts have been
      introduced to be used instead of metal alloys and ceramics. The aim of this study
      was to investigate the flexural properties of different types of FRC posts and
      compare those values with a novel FRC material for dental applications. METHODS:
      Seventeen different FRC posts of various brands (Snowpost, Carbopost, Parapost, C
      post, Glassix, Carbonite) and diameters, (1.0-2.1 mm) and a continuous
      unidirectional E-glass FRC polymerized by light activation to a cylindrical form
      (everStick, diameter 1.5 mm) as a control material were tested. The posts (n=5)
      were stored at room's humidity or thermocycled (12.000 x, 5 degrees C/55 degrees
      C) and stored in water for 2 weeks before testing. A three-point bending test
      (span=10 mm) was used to measure the flexural strength and modulus of FRC post
      specimens. RESULTS: Analysis of ANOVA revealed that thermocycling, brand of
      material and diameter of specimen had a significant effect (p<0.001) on the
      fracture load and flexural strength. The highest flexural strength was obtained
      with the control material (everStick, 1144.9+/-99.9 MPa). There was a linear
      relationship between fracture load and diameter of posts for both glass fiber and
      carbon fiber posts. Thermocycling decreased the flexural modulus of the tested
      specimens by approximately 10%. Strength and fracture load decreased
      approximately 18% as a result of thermocycling. SIGNIFICANCE: Considerable
      variation can be found in the calculated strength values of the studied post
      brands. Commercial prefabricated FRC posts showed lower flexural properties than
      an individually polymerised FRC material.

PMID- 14698770
TI  - The influence of storage and indenter load on the Knoop hardness of dental
      composites polymerized with LED and halogen technologies.
AB  - OBJECTIVES: The mechanical properties of light cured dental composites are
      greatly influenced by the light curing unit (LCU) used for the polymerization.
      Previous studies have shown that for some composites lower mechanical properties
      were obtained if light emitting diode (LED) LCUs were used for the polymerization
      instead of halogen LCUs. Previous studies have also shown that light cured
      composites improve their mechanical properties through a post-curing process
      after the initial illumination with the LCUs. Therefore, this study investigated
      the post-curing process, to ascertain if it can compensate for the lower
      mechanical properties of composites polymerized with LED LCUs. METHODS: The Knoop
      hardness was measured for four dental composites (Z100, Spectrum, Definite,
      Solitaire2) polymerized with an LED LCU (LED63 prototype) or a halogen LCU
      (Trilight), directly after the curing process and after 5 days of storage. In
      addition, the load on the indenter was varied from 200 to 400 gf to investigate
      the influence of the load on the measured hardness on the top and bottom of the 2
      mm thick samples. RESULTS: In general the Knoop hardness at the bottom of the
      stored samples, cured with the LED LCU, was the same or statistically
      significantly greater than for the samples cured with the halogen LCU. A
      statistically significantly lower (p<0.0001) Knoop hardness was obtained on the
      top of the samples if the composite Definite was polymerized with the LED LCU
      instead of the halogen LCU. The load of 200 or 400 gf on the indenter had a
      statistically significant influence (p<0.0001) on the measured Knoop hardness for
      the composite Z100. The Knoop hardness measured with an indenter load of 400 gf
      increased statistically significantly (p<0.0001) for all composites after the 5
      days' storage, whether cured with the LED LCU or halogen LCU. SIGNIFICANCE: The
      post-curing effect cannot compensate for the lower hardness of composites
      containing co-initiators if polymerized with an LED LCU instead of a halogen LCU.
      The indenter load had a statistically significant influence on the measured Knoop
      hardness of composites and has the potential to falsify results if not selected
      carefully.

PMID- 14698772
TI  - Effects of saliva contamination on resin-resin bond strength.
AB  - OBJECTIVE: The purpose of this study is to evaluate the effects of saliva
      contamination on microtensile bond strength (microTBS) between resin interfaces
      and to determine which decontamination methods best re-established the original
      resin-resin bond strength. MATERIALS AND METHODS: Ninety-six light-cured resin
      composite cylinders of Z-250, Renew, Clearfil APX, and Pertac II were randomly
      divided into six groups. For each material, one group of specimens was not
      contaminated, serving as the control. For the other specimens, the top surface of
      each block was treated with saliva that was slowly dried (Treatment 1); dried
      forcefully (Treatment 2); slowly dried, rinsed, and dried (Treatment 3); slowly
      dried, rinsed, dried, and bonded with Single Bond, One-Step, Clearfil SE Bond, or
      Prompt L-Pop (Treatment 4); or slowly dried, but not rinsed, and bonded using the
      same adhesives (Treatment 5). Two 2-mm increments of resin composite were applied
      and light-cured. After 24 h, the assemblies were trimmed for microtensile bond
      testing and were loaded to failure at 1 mm/min. Data were analyzed using two-way
      and one-way ANOVA and Fisher's PLSD (p<0.05). RESULTS: Control values ranged from
      45.1 MPa for Pertac II to 71.5 MPa for APX. Treatment 1 caused significant
      reduction in resin-resin bond strength for all materials tested but for two of
      the materials in treatment 2. Pertac II was the only material that did not show a
      statistical difference from control group for treatment 3. Treatment 4 re
      established the control values for Z-250 and Renew and treatment 5 was the only
      one to show no statistical difference for all materials tested. SEM observation
      revealed a smooth surface in treatment 1, but treatment 3 showed a few craters.
      Treatment 4 and 5 showed a mixture of cohesive failure in the composite and
      adhesive. SIGNIFICANCE: The most reliable method for decontaminating saliva from
      resin surfaces involves the application of adhesives.

PMID- 14698773
TI  - Mechanical properties of glass ionomer cements affected by curing methods.
AB  - OBJECTIVE: The primary objective of the study was to assess the influence of
      externally applied 'command' set applications on the mechanical properties of
      several commercially available conventional glass ionomer cement (GIC). METHODS:
      Four different restorative GICs cements (Fuji IX FAST, Fuji IX, Ketac Molar
      Quick, Ketac Molar) were cured using three different methods, e.g. standard
      curing conditions (SC), ultrasonic excitation (UC) and by an external heat source
      (HC). The compressive strength of these samples was measured and the groups were
      compared using one-way ANOVA. A standard thermocouple (K-type) measured the
      temperature in GIC during curing. RESULTS: In general all experiments showed an
      increase in strength going from SC, UC to HC. Especially, the compressive
      strength of Fuji IX FAST and Ketac Molar increased by UC and HC compared to the
      SC values. The compressive strength of Fuji IX FAST as a function of time showed
      an increase in strength during 28d. There was a clear relationship between the
      temperature in the sample (SC<UC<HC) and the compressive strength of the GICs.
      SIGNIFICANCE: An increase in strength was found, especially at the early curing
      time. Enhanced material properties at early curing time can improve the survival
      rate of GICs in the clinical situation. Ultrasonic excitation can be used as a
      'command' set method and improves the properties of GIC at early setting time.

PMID- 14698774
TI  - Determining the slow crack growth parameter and Weibull two-parameter estimates
      of bilaminate disks by constant displacement-rate flexural testing.
AB  - OBJECTIVES: This study examined the influence of displacement-rate and relative
      layer heights (RLH) on the slow crack growth exponent and Weibull two-parameter
      estimates of bilayered ceramic composite disks composed of In-Ceram Alumina and
      Vitadur Alpha porcelain. METHODS: Equibiaxial disks were fabricated with RLH of
      1:2, 1:1 and 2:1, for In-Ceram Alumina and Vitadur Alpha porcelain, respectively.
      Ninety specimens each (30 1:2, 30 1:1, and 30 2:1) were tested in an equibiaxial
      ring-on-ring testing apparatus at displacement-rates of 0.127, 1.27 and 12.7 mm
      min(-1). RESULTS: Weibull parameters were statistically significantly affected by
      changes in RLH at a constant displacement-rate and the slow crack growth
      parameters were significantly affected by RLH. Many specimens exhibited
      nonbrittle failure modes. Nonbrittle failures usually exhibited a fall, followed
      by a rise in load prior to catastrophic failure, and most occurred in specimens
      with thicker cores at low displacement-rates. SIGNIFICANCE: Geometries of layered
      materials may affect their reliability and longevity.

PMID- 14698775
TI  - In vitro contact wear of dental composites.
AB  - OBJECTIVE: The aim of this study is to determine the in vitro two-body contact
      wear mechanisms of three medium filled composites and compare these with a highly
      filled composite previously investigated. MATERIALS AND METHODS: Three commercial
      dental composites with filler mass fraction loading of 75-76% were evaluated. Two
      of the composites contained Ba-B-Al-silicate glass fillers and fumed silica with
      different particle sizes and distributions. One of these composites contained a
      fairly uniform distribution of filler particles ranging in size from 1 to 5
      microm, whereas the particle size distribution in the second composite was
      bimodal consisting of small (less than 1 microm) and large (about 10 microm)
      particles. The third composite contained Ba-Al-silicate glass and silica with a
      filler particle size of approximately 1 microm. The composite disks were tested
      for wear against harder alumina counterfaces. Wear tests were conducted in
      distilled water using a pin-on-disk tribometer under conditions that represented
      typical oral conditions (sliding speed of 2.5 mm/s and contact loads ranging from
      1 to 20 N). The wear tracks were analyzed by scanning electron microscopy (SEM)
      and Fourier transform infrared (FTIR) spectroscopy to elucidate the wear
      mechanisms. The chemical composition of the water solution collected after the
      tests was determined using an inductively coupled plasma-mass spectrometer (ICP
      MS) to detect possible chemical changes, e.g. dissolution of trace elements due
      to submersion or wear. The wear results were compared with those reported in an
      earlier study on a highly filled composite containing predominately alumino
      silicate glass fillers and alumina at a filler loading of 92%. RESULTS: The
      differences in two-body wear rates between the three medium filled composites
      were not statistically significant (p<0.05) indicating that the variations in
      filler particle size and slight differences in chemical composition of the glass
      fillers do not affect the in vitro wear rates of these composites. Wear rates of
      these medium filled composites, however, were significantly lower than the highly
      filled composite (p<0.05). SEM, FTIR and ICP-MS analyses suggested that wear in
      the medium filled composites occurs by a complex set of processes involving
      tribochemical reactions between filler particles and water, formation of surface
      films containing a mixture of filler fragments and reaction products, and film
      delamination, as well as dissolution of the reaction products. SIGNIFICANCE: This
      study reveals that subtle changes in the filler particle size and small
      differences in filler composition do not significantly affect the two-body wear
      behavior of medium filled composites. However, the chemistry of filler particles
      plays an important role in altering the wear performance of composites when
      significant changes are made in the chemical composition of the fillers and when
      the filler loading is increased.

PMID- 14698776
TI  - Performance of two blue light-emitting-diode dental light curing units with
      distance and irradiation-time.
AB  - OBJECTIVES: To assess the performance of two blue light-emitting-diode (LED)
      curing units, in terms of their spectral output and irradiance and the depth of
      cure (dcure) produced in standard hybrid and modified composites, compared with a
      conventional quartz tungsten halogen (QTH) light curing unit. METHODS: The
      following light curing units (LCUs) were studied: Elipar-Freelight-1 LED (LED-1)
      3 M-ESPE, Ultralume-2 LED (LED-2) Optident, and the Optilux-500 QTH (QTH-1)
      Sybron-Kerr. For each LCU, using a UV-visible spectrophotometer, the output
      spectrum was measured and the irradiance of emitted light as a function of source
      detector distance. Three composites were studied of similar formulation but
      differing in their initiator concentrations and/or opacity. These were: Tetric
      Ceram (A3), Tetric Ceram HB containing an additional photoinitiator responding to
      approximately 435 nm (A3) and Tetric Ceram Bleach (L). dcure was measured using a
      calibrated digital needle-penetrometer, as a function of source-specimen distance
      and for irradiance periods of 10, 20 and 40 s. RESULTS: Each unit delivered a
      single peak in the blue region of the visible spectrum. The wavelength maxima for
      LED-1, LED-2 and QTH-1 were 486.4, 458.2 and 495.2 nm, respectively. Cure-depth
      (dcure) values varied significantly (p<0.001) with irradiance times and source
      specimen distance for both LED and QTH sources. The percentage reduction in dcure
      values resulting from LED versus QTH irradiance increased with source-specimen
      distance. SIGNIFICANCE: The LED-LCUs had an energy-efficient spectral output for
      conventional composite curing but had a lower irradiance compared with the QTH
      LCU, leading to reduced performance in depths of cure. Design improvements to
      provide greater irradiance from the LED-1 and to a lesser extent LED-2, should
      result in increased performance.

PMID- 14698777
TI  - Second generation LEDs for the polymerization of oral biomaterials.
AB  - OBJECTIVES: New blue, so called second generation light emitting diodes (LEDs)
      are now available with a high optical power output. These LEDs will potentially
      find widespread application in commercially available light curing units (LCUs).
      This study, therefore, investigated the curing performance of a prototype LCU
      containing one high power LED and a conventional halogen LCU (Polofil). METHODS:
      The performances of the LCUs were evaluated by measuring the Knoop hardness and
      depth of cure of the composites. Three dental composites were selected (Z100,
      Admira and Revolcin Flow) in a light (A2) and a dark shade (A3.5 or A4),
      respectively, and were polymerized for 40 s each. RESULTS: The LED prototype
      (irradiance=901 mW/cm2) achieved a statistically significantly greater (p<0.05)
      depth of cure than the halogen LCU (irradiance=860 mW/cm2) for all composites.
      Generally, there was no statistically significant difference in Knoop hardness on
      the top and bottom of a 2 mm thick disk for the composites Z100 and Admira if
      polymerized with the LED prototype or halogen LCU. The composite Revolcin Flow,
      however, showed in general a statistically significant lower Knoop hardness if
      polymerized with the LED LCU. SIGNIFICANCE: The present study shows that second
      generation LEDs have the potential to replace halogen LCUs if the composites are
      selected carefully. Furthermore, this study confirmed that the depth of cure test
      does not discriminate between LCU's performance for composites containing co
      initiators, but the Knoop hardness test does.

PMID- 14698778
TI  - Polymerization shrinkage-strain kinetics of temporary crown and bridge materials.
AB  - OBJECTIVE: The purpose of this study was to measure the polymerization shrinkage
      kinetics of four commercially available polymer-based temporary crown and bridge
      materials, including the effect of ambient temperature. METHODS: Three
      dimethacrylate-based materials and one monomethacrylate-based material were
      investigated. The polymerization shrinkage-strains were measured by using the
      Bonded-disk method with initial specimen temperature at both 23 and 37 degrees C,
      with values particularly noted at 5, 10, and 120 min after mixing. Five
      recordings were taken for each material. The progress of the setting reaction and
      its temperature-dependence were evaluated by the kinetic curves, and net
      shrinkage and total shrinkage (inclusive of expansion magnitude) of each material
      were compared by independent sample t-test and one-way ANOVA. RESULTS: Most
      shrinkage occurred in the first 10 min after mixing although there was an early
      expansion especially with the monomethacylate in the first 5 min. At 120 min, the
      net shrinkage-strain at 23 and 37 degrees C of the materials used in this test
      ranged from 3.54 to 4.13%. The fastest setting dimethacrylate-based material and
      the monomethacrylate-based material showed higher shrinkage-strain than other
      materials. No significant differences of net shrinkage-strain were found between
      23 and 37 degrees C, but higher shrinkage rates were measured at 37 degrees C
      than at 23 degrees C. SIGNIFICANCE: The Bonded-disk method is a suitable method
      for measuring temperature-dependence of shrinkage-strain of polymer-based
      temporary materials. The dimethacrylate-based materials are preferable to
      monomethacrylates for temporary restoration as judged by the magnitude of
      polymerization shrinkage-strain, the majority of which is apparent within 10 min
      from the start of mixing and may affect the clinical outcome.

PMID- 14698779
TI  - Effect of energy density on properties and marginal integrity of posterior resin
      composite restorations.
AB  - OBJECTIVES: The purpose of this study was to determine the minimal extent of cure
      required by the base of a Class 2 resin composite restoration (Z250, 3M ESPE, St
      Paul, MN, USA) that allows it to support the rest of the restoration and maintain
      its marginal seal under simulated clinical conditions. METHODS: Resin composite
      (Z250, 3M ESPE, St Paul, MN, USA) was placed incrementally or in bulk into Class
      2 preparations in extracted human molar teeth and exposed to various light-curing
      energy densities. The restorations were subjected to 1000 thermal cycles (5-55
      degrees C) and 500,000 fatigue cycles from 18 to 85 N using a stainless-steel
      sphere. Marginal integrity was evaluated using visual rating (ridit analysis) and
      microleakage. Degree of conversion (DC) and Knoop hardness (KHN) were determined
      at the occlusal and gingival surfaces using a reusable tooth template with
      identical preparation dimensions. Percentage of maximum DC and KHN were
      determined. Mechanical properties were tested in resin composite bars having
      similar KHN values as the resin composite at the gingival margins. RESULTS:
      Energy density had a significant effect on gingival marginal defects as
      determined by ridit analysis but not on microleakage. Water had a significant
      dissolving effect on gingival margin integrity at very low degrees of conversion
      and energy densities (4000 mJ/cm2). There was no overall significant effect of
      thermal-mechanical stressing on gingival marginal defects or microleakage.
      SIGNIFICANCE: Based on ridit analysis, a recommended lower limit of gingival
      margin acceptability in the bulk-filled Z250 resin composite restoration was
      created by 80% of maximum conversion, 73% of maximum hardness and approximately
      70% of maximum flexural strength and modulus in the gingival marginal area.

PMID- 14698781
TI  - From bench to bedside.

PMID- 14698782
TI  - PET measures of pre- and post-synaptic cardiac beta adrenergic function.
AB  - Positron Emission Tomography was used to measure global and regional cardiac beta
      adrenergic function in 19 normal subjects and 9 congestive heart failure
      patients. [(11)C]-meta-hydroxyephedrine was used to image norepinephrine
      transporter function as an indicator of pre-synaptic function and [(11)C]
      CGP12177 was used to measure cell surface beta-receptor density as an indicator
      of post-synaptic function. Pre-synaptic, but not post-synaptic, function was
      significantly different between normals and CHF patients. Pre-synaptic function
      was well matched to post-synaptic function in the normal hearts but significantly
      different and poorly matched in the CHF patients studied. This imaging technique
      can help us understand regional sympathetic function in cardiac disease.

PMID- 14698784
TI  - The folate receptor as a molecular target for tumor-selective radionuclide
      delivery.
AB  - The cell-membrane folate receptor is a potential molecular target for tumor
      selective drug delivery, including radiolabeled folate-chelate conjugates for
      diagnostic imaging. We review here some background on the folate receptor as
      tumor-associated molecular target for drug delivery, and briefly survey the
      literature on tumor-targeting with radiolabeled folate-chelate conjugates.

PMID- 14698783
TI  - Dose-dependent biodistribution of [(99m)Tc]DTPA-mannosyl-dextran for breast
      cancer sentinel lymph node mapping.
AB  - [(99m)Tc]DTPA-mannosyl-dextran is a receptor-binding radiopharmaceutical
      specifically designed for sentinel lymph node mapping. The purpose of this study
      was to test the biodistribution and safety of [(99m)Tc]DTPA-mannosyl-Dextran at
      different molar doses. Twenty-four female breast cancer patients participated in
      this study. Four groups of 6 patients received an injection of 0.2, 1.0, or 5.0
      nmol of [(99m)Tc]DTPA-mannosyl-Dextran or filtered [(99m)Tc]sulfur colloid. The
      injection site clearance was monitored by dynamic imaging for three hours. Whole
      body scans were acquired at 2.5 and 12, and lymph nodes were assayed for
      radioactivity after gamma-guided sentinel lymph node biopsy. Injection site
      clearance of [(99m)Tc]DTPA-mannosyl-Dextran was not statistically different in a
      dose-dependent manner. Dose-dependent sentinel node uptake was observed (p =
      0.03). There were no clinically significant alterations in laboratory parameters
      among all dose levels at 4 h or 24 h post injection compared to preoperative
      levels. Radiation absorbed doses did not differ among the three dose levels, but
      were lower than filtered [(99m)Tc]sulfur colloid.

PMID- 14698785
TI  - Interpreting enzyme and receptor kinetics: keeping it simple, but not too simple.
AB  - The hyperbolic parabola is commonly used to summarize kinetics for enzyme
      reactions and receptor binding kinetics. Depending on the experimental
      conditions, certain assumptions are valid but others might be violated so that
      the parameters used to fit this hyperbolic function, the maximum asymptote and
      the equilibrium constant, require different interpretations. The first topic of
      this review compares enzyme-induced transformations and receptor binding in terms
      of the appropriate assumptions. The second topic considers the complication of
      adding a competitive inhibitor as an enzyme substrate or a receptor ligand and
      the subtleties of inferring the equilibrium dissociation constant from the
      concentration of inhibitor (for example unlabeled drug) that leads to the
      midpoint, IC(50,) of an inhibition curve. Receptor binding may be measured
      directly by a concentration assay or as a pharmacodynamic response variable.

PMID- 14698786
TI  - Identifiability analysis of second-order systems.
AB  - Models provide a means to represent our understanding of the interaction among
      the components of a system. Individual instantiations of a system are captured by
      allowing the model to have parameters that may be different for each
      instantiation. Included in the model is a representation of the means to observe
      certain aspects of a system. Given the observations, successful estimation of the
      parameters requires that the parameters be identifiable. This is an important
      consideration for potential use of the model in diagnostic medicine or analysis
      and planning of experiments. Models considered here are typical of those used to
      describe flows and concentrations associated with ligand-receptor interactions.

PMID- 14698788
TI  - Clinical application of TcGSA.
AB  - Asialoglycoprotein receptor (ASGP-R) is a hepatic cell surface receptor specific
      for galactose-terminated glycoprotein. The (99m)Tc-labeled asialoglycoprotein
      analog, TcGSA (galactosyl-human serum albumin-diethylenetriamine-pentaacetic
      acid) has been applied to human hepatic receptor imaging. This method is unique
      and provides information that is totally independent of the ICG test or Child
      Turcotte Score. However, simple parameters, HH15 or LHL15 are no better than
      conventional Child-Turcotte Score. Parameters obtained from kinetic modeling were
      useful in detecting liver cirrhosis or postoperative liver failure. They provide
      quantitative data on functioning liver mass. Considering the moderate cost and
      widespread availability of gamma cameras, a TcGSA test should be performed on
      patients whose liver function are not adequately estimated by an ICG test or a
      Child-Turcotte score.

PMID- 14698787
TI  - A review of graphical methods for tracer studies and strategies to reduce bias.
AB  - Graphical techniques provide simple methods for the analysis of data from tracer
      studies. They provide considerable ease of computation compared to the
      optimization of individual model parameters in the solution of the differential
      equations generally used to describe the binding of tracers. The theoretical work
      of Patlak which was applied to irreversible tracers formed the basis for
      extensions of graphical techniques to reversibly binding tracers. The advantage
      of graphical methods is that they are not dependent upon a particular model
      structure but provide a measure of tracer binding that can be interpreted in
      terms of a model structure if desired. They provide a visual way to distinguish
      the type of binding whether reversible or irreversible in the initial studies of
      new ligands. Conditions under which the graphical techniques can be applied are
      considered as well as problems encountered with slow binding components. One
      problem in the use of these methods particularly the method for reversible
      tracers is the bias generated due to the presence of statistical noise. Some
      recently proposed techniques for reducing the noise are considered.

PMID- 14698789
TI  - The use of gene-manipulated mice in the validation of receptor binding
      radiotracer.

PMID- 14698790
TI  - Gastrin releasing peptide (GRP) receptor targeted radiopharmaceuticals: a concise
      update.
AB  - The gastrin releasing peptide (GRP) receptor is becoming an increasingly
      attractive target for development of new radiolabeled peptides with diagnostic
      and therapeutic potential. The attractiveness of the GRP receptor as a target is
      based upon the functional expression of GRP receptors in several tumors of
      neuroendocrine origin including prostate, breast, and small cell lung cancer.
      This concise review outlines some of the efforts currently underway to develop
      new GRP receptor specific radiopharmaceuticals by employing a variety of
      radiometal chelation systems.

PMID- 14698791
TI  - Imaging the PCP site of the NMDA ion channel.
AB  - The N-methyl-D-aspartate (NMDA) ion channel plays a role in neuroprotection,
      neurodegeneration, long-term potentiation, memory, and cognition. It is
      implicated in the pathophysiology of several neurological and neuropsychiatric
      disorders including Parkinson's Disease, Huntington's Chorea, schizophrenia,
      alcoholism and stroke. The development of effective radiotracers for the study of
      NMDA receptors is critical for our understanding of their function, and their
      modulation by endogenous substances or therapeutic drugs. Since the NMDA/PCP
      receptor lies within the channel, it is a unique target and is theoretically
      accessible only when the channel is in the active and "open" state, but not when
      it is in the inactive or "closed" state. The physical location of the NMDA/PCP
      receptor not only makes it an important imaging target but also complicates the
      development of suitable PET and SPECT radiotracers for this site. An intimate
      understanding of the biochemical, pharmacological, physiological and behavioral
      processes associated with the NMDA ion channel is essential to develop improved
      imaging agents. This review outlines progress made towards the development of
      radiolabeled agents for PCP sites of the NMDA ion channel. In addition, the
      animal and pharmacological models used for in vitro and in vivo assessment of
      NMDA receptor targeted agents are discussed.

PMID- 14698792
TI  - In vivo molecular-genetic imaging: multi-modality nuclear and optical
      combinations.
AB  - Multi-modality, noninvasive in vivo imaging is increasingly being used in
      molecular-genetic studies and will soon become the standard approach for reporter
      gene imaging studies in small animals. The coupling of nuclear and optical
      reporter genes, as described here, represents only the beginning of a far wider
      application of this technology in the future. Optical imaging and optical
      reporter systems are cost-effective and time-efficient; they require less
      resources and space than PET or MRI, and are particularly well suited for imaging
      small animals, such as mice. Optical reporter systems are also very useful for
      the quantification and selection of transduced cells using FACS, and for
      performing in vitro assays to validate the function and sensitivity of
      constitutive and specific-inducible reporter systems. However, optical imaging
      techniques are limited by depth of light penetration and do not yet provide
      optimal quantitative or tomographic information. These issues are not limiting
      for PET- or MRI-based reporter systems, and PET- and MRI-based animal studies are
      more easily generalized to human applications. Many of the shortcomings of each
      modality alone can be overcome by the use of dual- or triple-modality reporter
      constructs that incorporate the opportunity for PET, fluorescence and
      bioluminescence imaging.

PMID- 14698793
TI  - Small animal imaging with high resolution single photon emission tomography.
AB  - Molecular imaging of small animals in vivo is vital in the study of mouse and rat
      models of human diseases, and will provide important clues to the pathogenesis,
      progression and treatment of many disorders. Functional imaging of small animals
      using ultra-high resolution single photon emission tomography (SPECT) should be a
      valuable tool in the molecular imaging armamentarium. SPECT has been used to
      study cerebral binding sites, to image the expression of reporter genes, and in
      applications in cardiology and oncology. In this review, we summarize the most
      recent developments in SPECT imaging of small animals, with particular reference
      to the types of systems available, their application, and some of the potential
      limitations.

PMID- 14698795
TI  - Predicting treatment noncompliance among criminal justice-mandated clients: a
      theoretical and empirical exploration.
AB  - Compliance with therapeutic regimens constitutes an important but infrequently
      studied precursor of treatment engagement and is a necessary condition of
      successful treatment. This study builds on recent treatment process research and
      provides a theory-driven analysis of treatment compliance. Five hypotheses are
      formulated to predict treatment noncompliance among criminal justice-mandated
      clients. These hypotheses tap different determinants of treatment progress,
      including physical prime, supportive social network, conventional social
      involvement, treatment motivation, and risk-taking propensity. Data from 150
      addicted felons participating in a diversion program are analyzed to test the
      hypotheses. Predictors related to these hypotheses correctly identify 58% of the
      fully compliant clients and 55-88% of the noncompliant clients. Most hypotheses
      are at least partially corroborated and a few strong correlates emerge across
      analyses. Clients in their physical prime, those with poorer social support, and
      those lacking internal desires for change were found especially likely to violate
      treatment program rules. Clinical implications are discussed.

PMID- 14698794
TI  - The role of family history in addiction severity and treatment response.
AB  - This study examined the relationship between familial history of substance use
      and addiction severity and treatment outcomes of opiate-dependent patients. The
      sample was comprised of 281 methadone maintenance patients at a VA or community
      based clinic. Using the family history section of the Renard Diagnostic
      Interview, three familial risk groups were identified based on patients' self
      report of their relatives' substance use. The three groups considered both the
      number and type (e.g., first vs. second degree) of biological relatives with a
      substance use problem. These three risk groups included: (1) high risk (HR, n =
      111), (2) medium risk (MR, n = 80), and (3) low risk (LR, n = 90). HR patients
      reported a history of more severe asocial behavior at baseline and they reported
      more medical problems and a greater degree of concurrent alcohol use both prior
      to and after 6 months of treatment compared to LR patients. In addition, the HR
      group reported more family/social problems at baseline compared to the MR and LR
      group and both HR and MR patients reported more psychological problems than LR
      patients after 6 months of treatment. However, when accounting for baseline
      differences, the regression analyses demonstrated that familial risk was not
      predictive of drug treatment outcomes after 6 months of methadone maintenance
      treatment.

PMID- 14698796
TI  - Specialized drug liaison midwife services for pregnant opioid dependent women in
      Dublin, Ireland.
AB  - The health needs of pregnant opioid dependent women are increasingly being
      recognized by health care professionals. These women generally receive limited
      antenatal care. Maternal and neonatal outcomes are also poorer compared to non
      drug using women. The number of pregnant opioid dependent women accessing drug
      treatment services in the Irish Republic has increased. A specialist Drug Liaison
      Midwife service was created in March 1999 to liaise between the three Dublin
      Maternity hospitals and the Drug Treatment Services. This paper surveys the first
      year of operation of one of these posts. It documents sociodemographic
      background, substance use, and medical histories of these women in addition to
      maternal and neonatal outcomes. Higher maternal methadone dose was associated
      with an increased risk of neonatal withdrawals among these women. The experience
      of this specialist liaison service indicates that it is possible to build
      effective working relationships between opioid dependent pregnant women and the
      Obstetric and Drug services involved in their care. This has resulted in benefit
      to these women, their children and the Irish Health Care system.

PMID- 14698797
TI  - The relationship of legal coercion to readiness to change among adults with
      alcohol and other drug problems.
AB  - Prior research on legally coerced treatment for substance abuse tends to find no
      difference between coerced and non-coerced clients with respect to treatment
      retention and treatment outcomes. There is less known about the relationship
      between coercion and a client's motivation to change. We considered the
      relationship of legal coercion and readiness to change among 295 consecutive
      admissions to five publicly funded outpatient treatment programs. A logistic
      regression analysis indicated that legal coercion was associated with greater
      readiness to change after controlling for addiction severity, prior treatment
      history, and gender. Persons entering treatment due to legal coercion were over
      three times more likely to have engaged in recovery-oriented behavior in the
      month preceding admission. Entering treatment more prepared to benefit from the
      experience could contribute to outcomes that are more positive.

PMID- 14698798
TI  - The effects of time and money prices on treatment attendance for methadone
      maintenance clients.
AB  - Many methadone maintenance clients are required to visit a clinic daily, so
      treatment attendance is essential for clients' compliance and treatment
      effectiveness. Using data derived from a unique survey, this study provides
      evidence of economic barriers to regular treatment attendance. Hypotheses tested
      are (1) higher personal costs reduce treatment attendance, and (2) willingness to
      pay (WTP) provides better time price estimates than wage rates. The findings
      suggest that both time and money function as rationing devices for methadone
      maintenance clients. The study finds WTP preferable to wage rate in measuring
      time price as evaluated by the effects of time price on treatment attendance.

PMID- 14698799
TI  - Modeling the use of innovations in private treatment organizations: the role of
      absorptive capacity.
AB  - Few studies have identified the organizational characteristics that are
      associated with the transfer of research-based treatment techniques into
      practice. One potentially fruitful concept is absorptive capacity, referring to
      an organization's ability to seek and utilize information, which may be
      positively associated with the use of innovative treatment techniques. This paper
      examines the associations between an additive measure of innovation use and three
      measures of absorptive capacity: environmental scanning, collection of
      satisfaction data, and the level of workforce professionalism. Data from a
      nationally representative sample of 322 privately funded substance abuse
      treatment centers indicate that treatment organizations use a greater number of
      innovations when they engage in more environmental scanning, survey referral
      sources, and third party payers for satisfaction, and have a more professional
      workforce. These results indicate the importance of absorptive capacity in
      predicting organizational innovativeness.

PMID- 14698800
TI  - Twelve-month maintenance treatment of opium-dependent patients.
AB  - The goal of this study was to compare the effects of 1, 3 and 8 mg per day doses
      of buprenorphine in the maintenance treatment of opium-dependent subjects in Iran
      over a treatment period of 12 months. Participants were randomized to three equal
      groups (171 subjects per group) of opium-dependent individuals who met the DSM-IV
      criteria for opioid dependence and were seeking treatment. They were treated in
      an urban outpatient clinic, offering a 1-hour weekly individual counseling
      session. Overall, 282 subjects (55%) completed the 12 months study. Completion
      rates by dosage group were 46 (26.9%) for the 1 mg dose group, 102 (59.6%) for
      the 3 mg dose group, and 134 (78.4%) for the 8 mg dose group (p =.000). These
      findings are consistent with previous reports of effective buprenorphine use in
      western countries as a suitable maintenance treatment for opium dependence.

PMID- 14698801
TI  - View of a young biogerontologist on the in vitro biogerontological model systems.

PMID- 14698802
TI  - Living forever and dying in the attempt.
AB  - Since the first cell culture was set at the beginning of the twentieth century it
      was believed that all cultured cells, if provided with the proper conditions,
      would replicate indefinitely. Sixty years later we overthrew this dogma by
      finding that normal cells have a finite capacity to replicate and that only
      abnormal or cancer cell populations can replicate indefinitely. We interpreted
      these findings to bear on our understanding of the aging process. If, as had been
      previously thought, normal cells can replicate indefinitely, then age changes
      could not have an intracellular origin. Our findings demonstrated that, on the
      contrary, age changes do have an intracellular origin. The hundreds of changes
      that were subsequently found to precede the loss of replicative capacity have
      been interpreted to be age changes and the finitude of replication to be an
      expression of longevity determination. Subsequent findings by others have
      determined the molecular mechanism that governs the finitude of normal cell
      replicative capacity and how immortal cancer cells escape this inevitability.
      Thus, key events in our understanding of aging, longevity determination and
      cancer have been revealed.

PMID- 14698803
TI  - In vitro senescence of immune cells.
AB  - Immune cells are eminently suitable model systems in which to address the
      possible role of replicative senescence during in vivo aging. Since there are
      more than 10(8) unique antigen specificities present within the total T
      lymphocyte population of each individual, the immune response to any single
      antigen requires massive clonal expansion of the small proportion of T cells
      whose receptors recognize that antigen. The Hayflick Limit may, therefore,
      constitute a barrier to effective immune function, at least for those T cells
      that encounter their specific antigen more than once over the life course.
      Application of the fibroblast replicative senescence model to the so-called
      cytotoxic or CD8 T cell, the class of T cells that controls viral infection and
      cancer, has revealed certain features in common with other cell types as well as
      several characteristics that are unique to T cells. One senescence-associated
      change that is T cell-specific is the complete loss of expression of the
      activation signaling surface molecule, CD28, an alteration that enabled the
      documentation of high proportions of senescent T cells in vivo. The T cell model
      has also provided the unique opportunity to analyze telomere dynamics in a cell
      type that has the ability to upregulate telomerase yet nevertheless undergoes
      senescence. The intimate involvement of the immune system in the control of
      pathogens and cancer as well as in modulation of bone homeostasis suggests that
      more extensive analysis of the full range of characteristics of senescent T cells
      may help elucidate a broad spectrum of age-associated physiological changes.

PMID- 14698804
TI  - Molecular mechanisms of replicative senescence in endothelial cells.
AB  - As human somatic cells age, they stop replicating and enter an irreversible state
      of growth arrest known as replicative senescence. Senescent cells are viable,
      metabolically active, and display altered gene and protein expression compared to
      proliferating cells. Endothelial cells, both in vitro and in vivo, are known to
      undergo senescence. As endothelial cells are a critical component of the
      vasculature, senescence of these cells can have a significant impact of vascular
      integrity, function, and overall homeostasis. This review will summarize recent
      work to understand the molecular mechanisms of endothelial cell senescence and
      the resulting alterations in gene/protein expression in these cells. Endothelial
      cell senescence will then be discussed in the context of disease development with
      a focus on atherosclerosis, an important age-associated disease of the
      vasculature.

PMID- 14698805
TI  - Replicative senescence and the art of counting.
AB  - The idea that aging is largely the result of (endogenous) stress appears to be at
      odds with the concept of biological 'clocks', which seem to programme and
      terminate cellular aging processes. Here, data are reviewed that show that
      telomeres, the major clock identified in human cells so far, do in fact measure
      stress and damage accumulation much more than simple mitotic time. Telomere
      shortening is significantly stress-dependent due to a telomere-specific damage
      repair deficiency. This identifies telomere-driven human cell replicative
      senescence as a stress response with high potential importance for human aging.

PMID- 14698806
TI  - Photoaging as a consequence of natural and therapeutic ultraviolet irradiation-
      studies on PUVA-induced senescence-like growth arrest of human dermal
      fibroblasts.
AB  - Premature aging of the skin is a prominent side effect of psoralen
      photoactivation, a therapy widely and successfully used for different skin
      disorders. Recently, we demonstrated that treatment of fibroblasts with 8
      methoxypsoralen and ultraviolet A irradiation resulted in growth arrest with
      morphological and functional changes reminiscent of replicative senescence. In
      this minireview we will focus on the similarities between intrinsic and extrinsic
      aging and PUVA-induced senescence-like growth arrest both resulting in the loss
      of the structural integrity of the dermal connective tissue as a hallmark of
      intrinsic aging and photoaging (extrinsic aging) of the skin, and we will discuss
      the important role of oxidative stress related telomere attrition in the PUVA
      induced phenotype of dermal fibroblasts. With the PUVA-induced growth arrest of
      fibroblasts a new model has been added to the growing number of in vitro models
      with longterm growth arrest upon exposure to sublethal stressors (i.e. hyperoxia,
      hydrogen peroxide, ethanol), which are characterized by morphological and
      functional changes common for cellular senescence. This model may be particularly
      suited for further studies addressing mechanisms of stress-induced senescence
      like growth arrest in vitro and in vivo, since many dermatological patients are
      treated with PUVA allowing the analysis of putative stress-induced premature
      senescence in vivo.

PMID- 14698807
TI  - Involvement of Rel/NF-kappa B transcription factors in senescence.
AB  - Senescence is now established as a genetically controlled phenomenon that alters
      different cell functions, including proliferation, apoptosis, resistance to
      stress, and energetic metabolism. Underlying changes in gene expression are
      governed by some transcription factors, whose expression or activity must change
      with senescence as well. Transcription factors of the Rel/NF-kappa B family are
      good candidates to participate in the establishment of senescence. Arguments
      range from correlation between cell functions controlled by these factors and
      cell functions altered during senescence, to phenotypes resulting from in vitro
      manipulations of Rel/NF-kappa B activity.

PMID- 14698808
TI  - Replicative enzymes, DNA polymerase alpha (pol alpha), and in vitro ageing.
AB  - Normal cells in culture are used to investigate the underlying mechanisms of DNA
      synthesis because they retain regulatory characteristics of the in vivo
      replication machinery. During the last few years new studies have identified a
      number of genetic changes that occur during in vitro ageing, providing insight
      into the progressive decline in biological function that occurs during ageing.
      Maintaining genomic integrity in eukaryotic organisms requires precisely
      coordinated replication of the genome during mitosis, which is the most
      fundamental aspect of living cells. To achieve this coordinated replication,
      eukaryotic cells employ an ordered series of steps to form several key protein
      assemblies at origins of replication. Major progress has recently been made in
      identifying the enzymes, and other proteins, of DNA replication that are
      recruited to origin sites and the order in which they are recruited during the
      process of replication. More than 20 proteins, including DNA polymerases, have
      been identified as essential components that must be preassembled at replication
      origins for the initiation of DNA synthesis. Of the polymerases, DNA polymerase
      alpha-primase (pol alpha) is of particular importance since its function is
      fundamental to understanding the initiation mechanism of eukaryotic DNA
      replication. DNA must be replicated with high fidelity to ensure the accurate
      transfer of genetic information to progeny cells, and decreases in DNA pol alpha
      activity and fidelity, which are coordinated with cell cycle progression, have
      been shown to be important facets of a probable intrinsic cause of genetic
      alterations during in vitro ageing. This has led to the proposal that pol alpha
      activity and function is one of the crucial determinants in ageing. In this
      review we summarize the current state of knowledge of DNA pol alpha function in
      the regulation of DNA replication and focus in particular on its interactive
      tasks with other proteins during in vitro ageing.

PMID- 14698809
TI  - The emerging role of epigenetics in cellular and organismal aging.
AB  - Genome modifications resulting from epigenetic changes appear to play a critical
      role in the development and/or progression of cancer. Scatter experimental
      evidence suggests that epigenetic changes could also be critical determinants of
      cellular senescence and organismal aging. Here we review the current evidence and
      discuss how imbalances in chromatin remodelers might trigger irreversible growth
      arrest in proliferating cells and tissues. Experimental data using drugs that
      target specific chromatin remodeling enzymes suggest that such approach could
      lead to the development of novel therapeutic modalities for the prevention or
      amelioration of some age-related dysfunctions.

PMID- 14698810
TI  - In vitro models of age-related neurodegenerative disorders.
AB  - Aging is the major risk factor for numerous brain diseases. This is especially
      true for Alzheimer's disease (AD), a peculiar neurodegenerative disorder in that
      it results from the synergy of two simultaneous but distinct degenerating
      processes: A beta and tau pathologies. For AD, and for most neurodegenerative
      disorders, aggregation of full length or truncated proteins, in neurons or glial
      cells, or in the parenchyma, is central, but still a mystery. In addition, the
      late onset of these pathologies links them to ageing processes. Cause or
      consequence? Experimental models, that allow us to dissect these
      pathophysiological defects, are presented.

PMID- 14698811
TI  - Can we say that senescent cells cause ageing?
AB  - Replicative senescence, the irreversible loss of proliferative capacity, is a
      common feature of somatic cells derived from many different species. The
      molecular mechanisms controlling senescence in mammals, and especially in humans,
      have now been substantively elucidated. However, to date, attempts to link the
      senescence of cells with the ageing of the organisms they comprise has not met
      with any similar degree of success, largely due to a lack of systematic
      investigation and the absence of the necessary biochemical tools. This review
      will summarise current data linking replicative senescence and organismal ageing.
      It will also suggest some essential tests of the cell senescence hypothesis and
      some necessary ground work which must be carried out before such tests can be
      fruitfully performed. It will not discuss the detailed molecular 'clockwork'
      controlling the decision to exit the cell cycle irreversibly because this is
      covered by other authors in this special issue.

PMID- 14698812
TI  - Introduction to animal models.

PMID- 14698813
TI  - Advantages and disadvantages of Caenorhabditis elegans for aging research.
AB  - The nematode Caenorhabditis elegans has been the organism of choice for most
      aging research, especially genetic approaches to aging. More than 70 longevity
      genes have been identified, with more to come, and these genes have been the
      subjects of intense study. I identify the major reasons for this and discuss
      limitations of this organism for future progress in research on aging.

PMID- 14698814
TI  - Comparative aspects of zebrafish (Danio rerio) as a model for aging research.
AB  - The zebrafish has emerged over the past decade as a major model system for the
      study of development due to its invertebrate-like advantages coupled with its
      vertebrate biology. These features also make it a potentially valuable organism
      for gerontological research. The main advantages of zebrafish include its
      economical husbandry, small yet accessible size, high reproductive capacity,
      genetic tractability, and a large and growing biological database. Although
      zebrafish life span is longer than rodents, it shares the feasibility of large
      scale mutational analysis with the extremely short-lived invertebrate models.
      This review compares zebrafish with the more widely used model organisms used for
      aging research, including yeast, worms, flies, mice, and humans.

PMID- 14698815
TI  - The retardation of aging by caloric restriction: its significance in the
      transgenic era.
AB  - The retardation of aging and diseases by caloric restriction (CR) is a widely
      studied and robust phenomenon. Recent publications describe transgenic and other
      mutant rodents displaying lifespan extension, and the rapid pace at which these
      animals are being generated raises the possibility that the importance of the CR
      paradigm is declining. Here we discuss these models and evaluate the evidence
      whether or not the aging process is retarded based on longevity, disease patterns
      and age-associated biological changes. A comparison to rodents on CR is made.
      Because CR has been investigated for approximately 70 years with increasing
      intensity, there exists extensive data to document aging retardation. In
      contrast, for nearly all of the genetically abnormal models of lifespan
      extension, such data are minimal and often unconvincing; additional studies will
      be required to validate these strains as suitable models for aging research.

PMID- 14698816
TI  - Genetic mouse models of extended lifespan.
AB  - Since 1996, seven genetic mouse models have been reported to show increased
      lifespan: Ames and Snell dwarf mice, the 'little mouse' (Ghrhr(lit/lit)), mice
      null for either growth hormone receptor/binding protein (GHR/BP(-/-)) or p66(shc)
      (p66(shc-/-)), mice heterozygous for the IGF-I receptor (Igf1r(+/-)), and fat
      specific insulin receptor knockout mice. In this article, we describe and
      evaluate these mouse models with respect to their relevance for aging studies.
      While these seven genetic models all show a significant increase in lifespan,
      issues of sample size and animal husbandry procedures require further evaluation
      before firm conclusions can be drawn on the reproducibility of life extension in
      most of these mouse models. Because data on the age-related pathology and
      physiological functions are lacking for all of the models, except the dwarf mice,
      it is too early to conclude that aging is retarded in these mouse models.
      However, these mouse models are already providing new information about the
      mechanism underlying mammalian aging.

PMID- 14698822
TI  - FIGO and the IJGO 2003 and 2004.

PMID- 14698817
TI  - Birds as long-lived animal models for the study of aging.
AB  - Despite their high lifetime energy expenditures, most birds can be characterized
      as long-lived homeotherms with moderately slow aging. A growing body of research
      confirms the prediction that birds have special adaptations for preventing aging
      related oxidative and glycoxidative damage. Nonetheless, biogerontologists have
      been slow to develop avian laboratory models. A number of domestic poultry and
      cage bird species represent either established or very promising animal models
      for studies of basic aging processes and their prevention, including degenerative
      neurobiological, behavioral and reproductive processes. Several kinds of birds
      have also been used in studies of cellular resistance to oxidative stressors in
      vitro. Results of preliminary studies on chickens and quail suggest that caloric
      restriction may extend the reproductive life span of hens, but its long-term
      effects on life span remain unstudied. Birds' innate anti-aging mechanisms may
      actually make them more suitable in some respects as models of longevity than
      short-lived laboratory rodents, and bird studies may ultimately reveal routes for
      therapeutic intervention in diseases of human aging and infertility.

PMID- 14698823
TI  - Pregnancy outcomes with increased nuchal translucency after routine Down syndrome
      screening.
AB  - OBJECTIVES: The purpose of this study was to evaluate the outcomes of pregnancies
      with nuchal translucency greater or equal to 3 mm for routine first trimester
      screening in unselected populations. METHODS: A total of 2980 pregnant women for
      first trimester ultrasonography were routinely offered crown-rump length (CRL)
      and nuchal translucency (NT) for screening for Down syndrome between 11 and 14
      weeks' gestation. A complete follow-up was obtained in all cases by a review of
      medical records. RESULTS: Using a cut-off value of 3 mm, the prevalence of
      increased fetal NT was 0.7% (n=22). Among the 22 cases, there were five (22.7%)
      chromosomal abnormalities. Of the 17 chromosomally normal pregnancies, four
      resulted in fetal demise (spontaneous abortion, intrauterine death or termination
      of pregnancy due to fetal abnormalities). The remaining 13 pregnancies resulted
      in live births, including one gestational hypertension and one preterm delivery,
      respectively. The total incidence of an adverse outcome in the group of increased
      fetal NT was 45.5%. CONCLUSIONS: In a routine population with first-trimester
      ultrasonography, fetal NT measuring greater than or equal to 3 mm was associated
      with a poor pregnancy outcome with not only chromosomal abnormalities and
      congenital cardiac diseases, but also poor maternal and fetal health or adverse
      pregnancy outcomes. In addition, this study also demonstrated the necessity for
      fetal assessment and follow-up in cases where the fetal NT is increased in the
      first trimester.

PMID- 14698824
TI  - Maternal and fetal outcome in valvular heart disease.
AB  - OBJECTIVES: To compare the pregnancy outcomes of women having valvular heart
      disease with the pregnancy outcomes of healthy women. METHODS: A retrospective
      comparison of the maternal and fetal pregnancy outcomes of 312 women with
      valvular heart disease and 321 healthy women cared for at a tertiary care
      hospital during the same period. Statistical analysis was done using the chi(2)
      test, with significance fixed at 0.05. RESULTS: Women with valvular heart disease
      had a significantly higher incidence of surgical interventions during pregnancy
      than women in the control group [13.4% (balloon mitral valvotomy) vs. 0.6%
      (ovarian cystectomy)], congestive heart failure (5.1% vs. 0%, P<0.001), and
      mortality [0.64% (two women) vs. 0%]. Perinatal outcome was also more adverse in
      the valvular heart disease group than in the control group, with increased
      preterm delivery rate (48.3% vs. 20.5%), reduced birth weight (2434+/-599 g vs.
      2653+/-542 g; P<0.001), and a higher incidence of APGAR scores less than 8 (8.3%
      vs. 4%; P<0.01). There was also a higher rate of instrumental delivery (9.9% vs.
      3.4%). However, the rate of cesarean deliveries was similar in the two groups.
      CONCLUSIONS: Pregnancy in women with valvular heart disease is associated with
      significantly higher maternal morbidity and adverse fetal outcomes and requires a
      team approach for optimal management.

PMID- 14698825
TI  - Drotaverine hydrochloride for augmentation of labor.
AB  - OBJECTIVES: To study the use of drotaverine hydrochloride for acceleration of
      labor and relief of labor pains. METHODS: In this double-blind placebo-controlled
      randomized study, 100 primigravidas in uncomplicated spontaneous labor at term
      were given drotaverine hydrochloride or placebo (distilled water)
      intramuscularly. Labor events, including pain (assessed by a visual analog scale
      and a verbal rating scale), neonatal outcome, and side effects of the drug were
      recorded. Student's t-test was used for analysis. RESULTS: Forty-four patients in
      the drug group and 40 in the placebo group had complete data for analysis after
      decoding. In drotaverine group, there was a mean 15% reduction in the duration of
      the first stage of labor and a mean 19% reduction in the second stage. The
      maximum shortening of the first stage (28%) was observed when drotaverine was
      administered when cervical dilatation was 4 cm (P=0.044). There were no adverse
      fetal effects, but atonic postpartum hemorrhage was more common in the
      drotaverine group. There was no relief of pain with the drug except in the fourth
      stage of labor. CONCLUSIONS: Drotaverine hydrochloride is safe and effective in
      accelerating labor, but not effective in lessening labor pain.

PMID- 14698826
TI  - A community-based obstetric ultrasound service.
AB  - OBJECTIVES: To investigate the impact of an ultrasound dating service on
      obstetric services. METHODS: A prospective trial with 3009 unselected women
      presenting for antenatal care at two Midwife Obstetric Units in a
      socioeconomically deprived urban area, South Africa. In the study unit, student
      ultrasonographers provided a basic ultrasound service. In the control unit,
      obstetric ultrasound was only available for specific indications. The main
      outcome measures were number of antenatal visits and referrals for fetal
      surveillance. RESULTS: The two cohorts were comparable except for the number of
      primigravidas but stratified analysis according to parity did not affect the
      results. Ultrasonography did not alter pregnancy outcome but reduced the number
      of perceived preterm labors/ruptured membranes (12.0 vs. 16.7%, P<0.003), post
      term deliveries (8.1 vs. 10.8%, P<0.04) and referrals for fetal surveillance
      [15.9 vs. 29.6%, P<0.000, RR 0.79 (0.71-0.88)]. CONCLUSIONS: This community-based
      basic ultrasound service significantly reduced referrals to a regional center for
      fetal surveillance and delivery.

PMID- 14698827
TI  - Maternal self-administered fetal heart rate monitoring and transmission from home
      in high-risk pregnancies.
AB  - OBJECTIVES: To evaluate the feasibility of high-risk pregnancy surveillance by
      patient-directed fetal heart rate monitoring and transmission, and to assess
      patient satisfaction with this technology. METHODS: Thirty-six women with high
      risk pregnancies performed daily non-stress tests at home and transmitted the
      data to our perinatal care center by telephone. At each transmission, patients
      were asked by a physician about perceived fetal movements and uterine
      contractions and given the results. If the tracing was unsatisfactory, further
      evaluation was performed. In addition, patients completed a questionnaire on
      quality of life and anxiety state before and after the study. RESULTS: All
      patients were able to perform the tests and transmissions. The quality of
      recorded data was significantly correlated with maternal body mass index, but not
      with gestational age at the time of monitoring or birth weight. Thirty-nine of
      the total 562 tracings (6.9%) were inconclusive or non-reassuring. After repeated
      testing, 32 of them (82%) were considered normal, and seven patients (18%) were
      referred for additional in-hospital evaluation. Of this group, four were
      discharged for further surveillance with routine home monitoring and the
      remaining three were hospitalized for continued evaluation. There were no
      significant immediate adverse maternal or neonatal outcomes as a result of the
      monitoring. Patient satisfaction was high. CONCLUSIONS: Daily home FHR monitoring
      in high-risk patients is safe and feasible at all gestational ages, based on this
      initial pilot evaluation. It is easily and reliably performed and accepted by
      patients with a high level of satisfaction.

PMID- 14698828
TI  - Chemical ablation of endometrium with trichloroacetic acid.
AB  - OBJECTIVES: The aim of this study was to assess the efficacy of topically applied
      trichloroacetic acid (TCA) for endometrial ablation in patients with
      dysfunctional uterine bleeding (DUB). This trial has also compared the advantages
      of prethinning the endometrium with danazol and goserelin acetate before ablation
      with TCA. METHODS: This prospective trial was conducted on 90 volunteer cases.
      Patients were allocated into three treatment groups comprised of 30 patients. In
      group I cases underwent dilatation and curettage before endometrial ablation. In
      group II cases were administered danazol before ablation. Cases in group III
      received goserelin acetate on the same day and 28 days after ablation.
      Endometrium was evaluated by biopsy, transvaginal ultrasonography and
      hysteroscopy. Endometrial ablation was performed with 95% TCA. All of the
      patients were evaluated 3 and 6 months after TCA application. RESULTS: After 6
      months of treatment, the success rate was recorded as 83% in the first group,
      92.3% in the second group and 96.6% in the third group. The mean length of
      uterine cavity was reduced in all groups, being only significant in Goserelin
      group (P<0.5). Endometrial thickness was decreased significantly in all treatment
      groups (P<0.001). CONCLUSIONS: This study concluded that endometrial ablation by
      TCA may readily be performed as an alternative treatment method in the management
      of DUB. Moreover, suppression of endometrium with danazol or especially with
      goserelin acetate before ablation, resulted in significant success rate.

PMID- 14698829
TI  - Pulmonary thromboembolism following gynecologic surgery and cesarean section.
AB  - OBJECTIVE: To investigate the incidence and risk factors of symptomatic pulmonary
      thromboembolism (PTE) in patients following gynecologic surgery or cesarean
      section in Japan. METHOD: We examined the clinical records of all patients who
      have undergone gynecologic surgery or cesarean section at 32 hospitals affiliated
      with the Tohoku University Hospital between 1990 and 1999. RESULT: The total
      number of gynecologic surgical procedures and cesarean sections were 61648 and
      26502, respectively. Twenty-five of the 88150 (0.028%) patients developed
      clinical PTE. Among the PTE patients who underwent gynecologic surgery, 86% were
      more than 40 years of age, 36% were obese (BMI>25 kg/m(2)) and 43% had uterine
      body cancer. Among the PTE patients who underwent cesarean section, 36% were more
      than 35 years of age and 55% were obese (BMI>29 kg/m(2)). CONCLUSION: Risk
      factors in Japanese patients undergoing gynecologic surgery may include age and
      cancer of the uterine body; risk factors for the development of PTE following
      cesarean section may include age and obesity.

PMID- 14698830
TI  - Endogenous urinary steroids in premenopausal women with uterine leiomyomas.
AB  - OBJECTIVES: To study the effect of endogenous steroids on the presence of uterine
      leiomyomas. METHODS: Urine samples of 27 premenopausal women with leiomyomas and
      25 age-matched healthy premenopausal women were collected. The concentration of
      estrogens and androgens in the urine samples of the two groups were determined
      using a gas chromatography mass spectrometer and the two groups were compared. To
      study metabolic changes in patients indirectly, the concentration ratios of
      precursor metabolite to product metabolite of the two groups were also compared.
      RESULTS: Urinary concentrations of 17beta-estradiol, 5-androstene-3beta, 16beta,
      17beta, triol, 11-keto-ethiocholanolone, 11beta-hydroxy-androsterone, 11beta
      hydroxy-etiocholanolone, THS, THA, THE, alpha-cortol and beta-cortol were
      significantly higher in patients than in controls. The concentration ratios of
      17beta-estradiol/estrone and 11/beta-hydroxy-ethiocholanolone/11beta-hydroxy
      androsterone increased in patients. CONCLUSIONS: The presence of uterine
      leiomyomas correlates with an increase in urinary concentrations of estrogens and
      androgens, and it appears to be caused by a decrease in patients' metabolism of
      steroids.

PMID- 14698831
TI  - Familial risk among Japanese patients with endometriosis.
AB  - OBJECTIVES: This study was designed to examine the prevalence of endometriosis
      among female siblings of patients with endometriosis in Japan. METHODS: A total
      of 339 patients with endometriosis were questioned about endometriosis in their
      sisters. The control group consisted of 284 Japanese healthy fertile women with
      no history of endometriosis. Similarly, the controls were interviewed about their
      sisters. RESULTS: We detected sisters with endometriosis in 8.8% of cases and
      1.5% of the control population. The relative risk of endometriosis in female
      siblings was 5.7. However, a significant difference was not seen in age at
      diagnosis and clinical stage between patients with or without a family history of
      endometriosis. CONCLUSIONS: These data demonstrate a familial tendency for
      endometriosis and suggest that endometriosis has a genetic factor in the
      pathogenesis.

PMID- 14698832
TI  - Resectoscopic treatment of complete longitudinal vaginal septum.
AB  - Every gynecologist can easily recognize vaginal abnormalities and the subsequent
      disturbances of sexual function, such as dyspareunia and apareunia, arising from
      them. In the case of congenital vaginal septum, it is extremely important to
      completely assess the abnormality before planning for surgical treatment. Because
      normal vaginal development is subsequent to the canalization and fusion of the
      two Mullerian ducts once vacuolization has occurred, but not their union, a
      duplication of different degree will be the consequence. If the defect is
      complete, a didelphys uterus with a double vagina will result. The aim of our
      report is to describe the endoscopic technique used to treat three cases of
      complete longitudinal vaginal septum and to highlight the main differences
      between our technique and the standard surgical procedure.

PMID- 14698833
TI  - Maternal complications of twin pregnancy.

PMID- 14698834
TI  - C-reactive protein and body mass index in women with pre-eclampsia.

PMID- 14698835
TI  - Cobalamin (vitamin B12) metabolism during pregnancy.

PMID- 14698836
TI  - Preferences for cesarean section or symphysiotomy for obstructed labor among
      Nigerian women.

PMID- 14698837
TI  - Vaginal treatment with povidone--iodine suppositories during pregnancy.

PMID- 14698838
TI  - Comparison of intramural myomectomy scar after laparotomy or laparoscopy.

PMID- 14698839
TI  - Sublingual misoprostol for second-trimester abortion.

PMID- 14698840
TI  - The effects of armed conflict on pregnancy outcomes in the Congo.

PMID- 14698841
TI  - Critical role of mast cells in inflammatory diseases and the effect of acute
      stress.
AB  - Mast cells are not only necessary for allergic reactions, but recent findings
      indicate that they are also involved in a variety of neuroinflammatory diseases,
      especially those worsened by stress. In these cases, mast cells appear to be
      activated through their Fc receptors by immunoglobulins other than IgE, as well
      as by anaphylatoxins, neuropeptides and cytokines to secrete mediators
      selectively without overt degranulation. These facts can help us better
      understand a variety of sterile inflammatory conditions, such as multiple
      sclerosis (MS), migraines, inflammatory arthritis, atopic dermatitis, coronary
      inflammation, interstitial cystitis and irritable bowel syndrome, in which mast
      cells are activated without allergic degranulation.

PMID- 14698842
TI  - Dual effects of morphine on permeability and apoptosis of vascular endothelial
      cells: morphine potentiates lipopolysaccharide-induced permeability and apoptosis
      of vascular endothelial cells.
AB  - Vascular endothelial cells (VEC) provide an essential protective barrier between
      the vascular system and underlying tissues. Using VEC barrier models of human
      coronary artery cells and human and rat brain microvascular endothelial cells, we
      investigated the mechanism by which morphine affects lipopolysaccharide (LPS)
      induced VEC permeability. We demonstrated that co-administration of morphine and
      LPS induced greater VEC apoptosis and permeability than morphine or LPS alone.
      The extent of induced apoptosis appeared to be cell-type dependent. Furthermore,
      RT-PCR analysis revealed that morphine and LPS up-regulated Fas expression. These
      data suggest potential crosstalk between the signaling pathways that mediate
      morphine- and LPS-triggered apoptosis in brain VEC.

PMID- 14698843
TI  - Antigenic profile of human recombinant PrP: generation and characterization of a
      versatile polyclonal antiserum.
AB  - We describe the quality of a rabbit polyclonal antiserum (Sal1) that was raised
      against mature human recombinant prion protein (rhuPrP). Epitope mapping
      demonstrated that the Sal1 antiserum recognized six to eight linear antigenic
      sites, depending on the animal species. The versatility of the antiserum was
      evident from the range of animal species and immunochemical techniques where it
      could be applied successfully. Antigen absorption studies revealed differences in
      the location and number of epitopes remaining after incubation with soluble or
      aggregated antigen.Our knowledge concerning immunoprophylaxis against prion
      diseases and the important role played by conformational changes of PrP is
      increasing rapidly. The findings reported here should add to this body of
      knowledge.

PMID- 14698844
TI  - Reduced susceptibility to kainic acid-induced excitoxicity in T-cell deficient
      CD4/CD8(-/-) and middle-aged C57BL/6 mice.
AB  - Kainic acid (KA)-induced hippocampal injury is a good model for studying human
      neurodegenerative diseases. To investigate the roles of immune cells and age
      related changes in neurodegeneration, we used this model to assess reactions in
      young and middle-aged wild-type and CD4/CD8(-/-) mice by intranasal
      administration of KA. We found that CD4/CD8-deficiency resulted in a significant
      reduction of the severity of clinical signs and pathological changes in KA
      treated young, but not in KA-treated middle-aged mice. Middle-aged wild-type mice
      had a similar reaction to KA insult as young and middle-aged CD4/CD8(-/-) mice.
      CD4/CD8(-/-) mice exhibited decreased locomotor and rearing activities as they
      approached to middle-aged state, which was not seen in wild-type mice. In
      addition, CD4/CD8-deficiency and increased age prevented KA-induced increase of
      both locomotor and rearing activities. The results suggest that a decline of
      immunological function is associated with aging, and both of them may contribute
      to the relative resistance to KA-induced neurotoxicity.

PMID- 14698845
TI  - Expression of interleukin-16 by microglial cells in inflammatory, autoimmune, and
      degenerative lesions of the rat brain.
AB  - Here we report a comparative analysis of interleukin-16 (IL-16) expression by
      microglial cells of the normal rat brain in trimethyltin (TMT) neurotoxicity,
      experimental autoimmune uveitis (EAU), encephalomyelitis (EAE), and viral
      infection (Borna disease, Borna disease virus) by immunohistochemistry. Striking
      differences were observed. In contrast to the human brain, IL-16 was not
      expressed constitutively in the rat brain. Remote activation of microglial cells
      of the optic tract in EAU did not result into IL-16 expression. TMT intoxication
      induced expression in microglial cells of the hippocampus. In EAE and BDV,
      massive IL-16(+) microglial cells could be seen. Thus, IL-16 is a descriptor of
      microglial cell activation that discriminates between different disease models,
      and might be a valuable marker for the detection of microglia activation in human
      and rat central nervous system (CNS) diseases.

PMID- 14698846
TI  - Proximity between 5-HT secreting enteroendocrine cells and lymphocytes in the gut
      mucosa of rhesus macaques (Macaca mulatta) is suggestive of a role for
      enterochromaffin cell 5-HT in mucosal immunity.
AB  - The involvement of serotonin (5-hydroxytryptamine; 5-HT) in immunoregulation has
      been well documented. Gut mucosa is a large reservoir of 5-HT most of which is
      attributed to gut endocrine cells. In this study, we examined the anatomical
      relationship among 5-HT immunoreactive cells and T and B lymphocytes in the gut
      mucosa of rhesus monkeys (Macaca mulatta). 5-HT, CD3 and CD20 immunoreactive
      cells were immunofluorescently labeled and visualized by confocal microscopy. 5
      HT immunoreactive cells were primarily found within the epithelium of the
      intestine and were present at all levels of the gastrointestinal tract. Many 5-HT
      immunoreactive cells were in contact with, or very close proximity to CD3(+) and
      CD20(+) lymphocytes. These results provide morphological evidence to suggest
      interactions between 5-HT secreting enteroendocrine cells and lymphocytes in the
      gut mucosa. This further supports a possible role of 5-HT in mucosal immune
      responses.

PMID- 14698847
TI  - c-Jun N-terminal kinase and, to a lesser extent, p38 mitogen-activated protein
      kinase regulate inducible nitric oxide synthase expression in hyaluronan
      fragments-stimulated BV-2 microglia.
AB  - Lower molecular weight of hyaluronan (HA) fragments are capable of activating
      macrophages to express a number of inflammatory mediators through the interaction
      with the HA receptor CD44. Recent evidence has demonstrated that concomitant
      induction of CD44 and HA synthase 2 (HAS-2) mRNA in microglia of the ischemic
      brain. However, the influence of HA fragments on the activation of microglia is
      poorly understood. In this study, we demonstrated that HA fragments induced
      inducible NO synthase (iNOS) expression in BV-2 microglia in a dose-dependent
      manner and was synergized with interferon-gamma (IFN-gamma). Moreover, HA
      fragments could induce the activation of p38 mitogen-activated protein kinase
      (MAPK), extracellular signal-regulated kinase (ERK1/ERK2), and c-Jun N-terminal
      kinase (JNK) in a time and dose-dependent fashion. The HA fragments-induced iNOS
      expression was suppressed by the selective inhibitors of JNK and, to a lesser
      extent, p38 MAPK. These results suggest that the induction of iNOS by HA
      fragments is significantly dependent on JNK than on p38 MAPK signaling pathways
      and support the hypothesis that HA fragments may be an important regulator in the
      activation of microglia at sites of ischemic brain.

PMID- 14698848
TI  - Induction of human IgM and IgG anti-GM1 antibodies in transgenic mice in response
      to lipopolysaccharides from Campylobacter jejuni.
AB  - Campylobacter jejuni lipopolysaccharides (LPS) are implicated in the development
      of autoantibodies to GM1 ganglioside in patients with neuropathy following C.
      jejuni infection. CjLPS bears oligosaccharides that are cross reactive with GM1
      ganglioside and presumably exerts its effects via molecular mimicry. To study the
      mechanisms that are involved in development of the autoantibody response, a
      transgenic mouse line was developed that expresses an IgM anti-GM1 antibody
      derived from a patient with multifocal motor neuropathy (MMN). In vivo
      stimulation of the transgenic mice with C. jejuni lipopolysaccharides (CjLPS),
      but not of wild-type mice readily elicited high serum titers of anti-GM1 IgM
      antibodies, followed by IgG anti-GM1 antibodies after two booster injections. In
      in vitro experiments, CjLPS stimulated the transgenic B-cells at lower
      concentration than control LPS. The increased sensitivity to CjLPS and the
      induction of IgG anti-GM1 by CjLPS but not control LPS are consistent with a
      mechanism of B-cell activation that involves both the LPS and the antigen
      specific surface Ig receptors, with possible participation of T-cells.

PMID- 14698849
TI  - Opposite effects of IFN beta on cytokine homeostasis in LPS- and T cell contact
      activated human monocytes.
AB  - Multiple sclerosis (MS) is an immune-mediated disease improved by interferon-beta
      (IFNbeta) therapy. IFNbeta may owe its anti-inflammatory property to its ability
      to induce interleukin-1 receptor antagonist (IL-1Ra) without triggering IL-1beta
      synthesis in human monocytes. Furthermore, we recently demonstrated that IFNbeta
      inhibits the production of IL-1beta and tumor necrosis factor-alpha (TNF) in
      human monocytes activated by cellular contact with stimulated T cells, a
      mechanism which we suspected of playing an important part in the pathogenesis of
      chronic inflammatory diseases including MS. Here we compare modulatory effects of
      IFNbeta on the production of proinflammatory cytokines (IL-1beta, IL-1alpha, TNF,
      and IL-6) and IL-1Ra in human monocytes stimulated by lipopolysaccharides (LPS)
      and isolated plasma membranes of stimulated T cells (msHUT), which are likely to
      reflect monocyte activation in acute and chronic inflammation, respectively. In
      monocytes activated by either LPS or msHUT, IFNbeta did not modulate the
      secretion of IL-1alpha and IL-6, but it enhanced the production of IL-1Ra in a
      dose-dependent manner. However, in monocytes activated by msHUT, the expression
      of cell-associated and intracellular IL-1alpha was inhibited by IFNbeta,
      correlating with the inhibition of IL-1alpha transcript. IFNbeta inhibited the
      expression (mRNA) and production (protein) of IL-1beta and TNF, while enhancing
      those of IL-1Ra in monocytes activated by msHUT. In contrast, in monocytes
      activated by LPS, IFNbeta enhanced the expression and production of IL-1beta,
      TNF, and IL-1Ra, suggesting that it did not display anti-inflammatory properties
      in these conditions. This study demonstrates that IFNbeta displays opposite
      effects depending on the type of activation of human monocytes, suggesting that
      it may affect different pathogenic mechanisms in opposite ways.

PMID- 14698850
TI  - Early activation of microglia as antigen-presenting cells correlates with T cell
      mediated protection and repair of the injured central nervous system.
AB  - After an injury to the central nervous system (CNS), activated microglia have
      been shown to contribute to the ongoing destructive processes leading to
      secondary neuronal degeneration. They can, however, also express neuroprotective
      activity. Studies from our laboratory point to the existence of a physiological T
      cell-mediated neuroprotective mechanism (adaptive immunity) that is amenable to
      boosting. We postulate that the beneficial or destructive outcome of the local
      microglial (innate) response is determined by a well-controlled dialog between
      the innate and the adaptive immune players. Here, we show that spontaneous or
      exogenously boosted T cell-mediated neuroprotection is correlated with early
      activation of microglia as antigen-presenting cells. We suggest that such
      microglial activity, if well controlled, is a crucial step in determining the
      fate of the neurons in a hostile environment.

PMID- 14698851
TI  - Presence of spinal B7.2 (CD86) but not B7.1 (CD80) co-stimulatory molecules
      following peripheral nerve injury: role of nondestructive immunity in neuropathic
      pain.
AB  - Previous work in our laboratory demonstrated spinal neuroimmune activation and
      leukocyte trafficking into the central nervous system (CNS) parenchyma in a rat
      model of neuropathic pain. Recent studies suggest that co-stimulatory molecules
      B7.1 (CD80) and B7.2 (CD86) play a differential role in the effect of beneficial
      versus deleterious CNS autoimmune responses. In the present study, we determined
      the lumbar spinal expression of the co-stimulatory molecules B7.1 and B7.2 in a
      rat model of neuropathy. We observed intense B7.2 microglial immunoreactivity in
      the lumbar spinal cord following the injury but no expression of B7.1. These data
      suggest a role of protective CNS autoimmunity following peripheral nerve injury.

PMID- 14698852
TI  - Neuronal expression of caspase-1 immunoreactivity in the rat central nervous
      system.
AB  - Caspase-1/interleukin-1beta (IL-1beta)-converting enzyme (ICE) cleaves IL-1beta
      and IL-18 precursor proteins to the active forms of these proinflammatory
      cytokines. Since both cytokines are constitutively expressed in the brain, we
      investigated whether this is also the case for caspase-1. Using an antibody
      raised against the p10-subunit of the active enzyme, constitutive expression of
      caspase-1 immunoreactivity was found in nerve cells in the arcuate nucleus and in
      nerve fibres throughout the brain. Co-localisation with alpha-melanocyte
      stimulating hormone was demonstrated. The distribution pattern of caspase-1
      immunoreactive structures is consistent with a role to produce mature IL-1beta in
      regions where IL-1beta mediates fever and sleep.

PMID- 14698853
TI  - IL-1 beta-mediated neuropeptide and immediate early gene mRNA induction is
      defective in Lewis hypothalamic cell cultures.
AB  - We previously found that Lewis (LEW/N) hypothalamic cells respond to interleukin
      1beta (IL-1beta) with reduced corticotropin-releasing hormone (CRH) and arginine
      vasopressin (AVP) peptide synthesis and secretion compared to Fischer (F344/N)
      cells. To investigate whether this peptide hyporesponsiveness in LEW/N cells is
      secondary to their deficient mRNA expression, temporal mRNA expression patterns
      of CRH, AVP, and several hypothalamic neuropeptides induced by IL-1beta in LEW/N
      and F344/N hypothalamic dissociated cell cultures were delineated by quantitative
      real-time polymerase chain reaction (RT-PCR). To investigate the molecular
      mechanisms underlying neuropeptide mRNA induction in cells of both strains,
      temporal mRNA expression patterns of immediate early genes (IEGs) and several
      signal transduction-associated molecules were also examined. We found that LEW/N
      hypothalamic cells were hyporesponsive to IL-1beta induction of neuropeptide and
      IEG mRNA, while LEW/N cells transcribed more IL-1 receptor and inducible nitric
      oxide synthase (iNOS) compared to F344N/N cells, suggesting that LEW/N and F344/N
      hypothalamic cells are differentially activated by IL-1beta.

PMID- 14698854
TI  - In vitro adrenergic modulation of cellular immune functions in experimental
      autoimmune encephalomyelitis.
AB  - OBJECTIVE: To analyze the effects in vitro of alpha- and beta-adrenoceptor
      agonists on splenocyte proliferation and on proinflammatory cytokine production
      in splenocytes and peritoneal macrophages (MF) in different stages of EAE.
      METHODS: Splenocytes and peritoneal macrophages were harvested in the acute phase
      of EAE and in remission, and from controls. The beta-agonist terbutaline, the
      alpha(1)-agonist methoxamine, and the alpha(2)-agonist UK-14304 were added with
      ConA or lipopolysaccharide (LPS). TNF-alpha and IFN-gamma contents in supernatant
      and splenocyte proliferation were determined. RESULTS: Terbutaline and UK-14304
      significantly suppressed TNF-alpha production by MF. However, EAE acute phase
      rats were resistant to the suppressive effect of UK-14304. Terbutaline
      significantly suppressed IFN-gamma and TNF-alpha production by splenocytes. EAE
      acute phase and remission animals showed reduced terbutaline-induced inhibition
      of IFN-gamma production. CONCLUSIONS: Disturbed sympathetic-immune communication
      in EAE is characterized by alterations in adrenergic sensitivity via both alpha-
      and beta-adrenergic pathways.

PMID- 14698855
TI  - B and T cells in the brains of autoimmune mice.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disorder that can involve the
      central nervous system (CNS). Recently, we reported the presence of
      autoantibodies bound to the brain tissue of murine models of lupus; MRL/lpr and
      BXSB. We postulated that the source of these autoantibodies was in part due to in
      situ production, caused by the entry of B and T cells. Frozen brain sections of
      MRL/lpr and BXSB at 1 and 4 months of age were stained for CD3 (T cells) and CD19
      (B cells) markers using an immunofluorescent antibody binding assay. Confocal
      fluorescence microscopy showed both CD3(+) and CD19(+) cells at 4 months of age
      only in MRL/lpr mice. There were no lymphocytes seen in the other autoimmune
      model, BXSB. Results suggest a difference in the mechanisms by which
      autoantibodies access the brain in these two autoimmune models of lupus.

PMID- 14698856
TI  - Coronavirus-induced demyelination occurs in the absence of CD28 costimulatory
      signals.
AB  - Infection of mice with mouse hepatitis virus (MHV) strain A59 results in acute
      encephalitis, hepatitis, and chronic demyelinating disease. T lymphocytes play an
      important role in MHV infection, and costimulatory signals are an important
      component of T cell function. To elucidate the role of the main costimulatory
      molecule, CD28, in MHV pathogenesis and demyelination, we examined the kinetics
      of MHV-A59 infection in CD28 knockout mice. MHV-A59-infected CD28 knockout mice
      developed acute encephalitis and hepatitis, and the same degree of chronic
      demyelination as normal C57Bl/6 (B6) mice. Thus, CD28, the costimulatory T cell
      molecule, is not required for MHV infection and MHV-induced demyelination.

PMID- 14698857
TI  - Androgens are protective in experimental autoimmune encephalomyelitis:
      implications for multiple sclerosis.
AB  - A gender difference prevails in some murine strains of experimental autoimmune
      encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). Our results
      showed that castration of SJL males, a strain characterized by decreased
      susceptibility of males as compared to females, displayed increased disease
      severity. In contrast, castration had no effect on disease in C57BL/6 males, a
      strain in which no gender difference in EAE is observed. Regardless of whether
      endogenous androgens were protective in a given genetic background, supplemental
      androgen treatment was protective in gonadally intact males of both strains.
      These data provide a basis for the novel therapeutic use of supplemental
      testosterone for men with MS.

PMID- 14698858
TI  - Antibody-mediated remyelination operates through mechanism independent of
      immunomodulation.
AB  - A set of antibodies capable of binding glial cells promotes remyelination in
      models of multiple sclerosis (MS). Within this set, the mouse antibody, SCH94.03,
      was immunomodulatory implying that immune system mobilization might be integral
      to remyelination. We evaluated whether the human remyelination-promoting antibody
      rHIgM22 influences acquired immunity. The antibody did not bind to immune cells,
      or influence humoral immune responses, antigen presentation, T cell proliferation
      or cytokine production. Treatment with rHIgM22 had no effect on demyelination or
      virus infection in two disease models. These results demonstrate that the
      remyelination-promoting activity of antibody rHIgM22 is not dependent on
      immunomodulation.

PMID- 14698859
TI  - CD95 polymorphisms are associated with susceptibility to MS in women. A
      population-based study of CD95 and CD95L in MS.
AB  - CD95/CD95L interaction results in activation-induced apoptosis thereby regulating
      clonal expansion of T cells outside the thymus. Genetic defects in this system
      result in autoimmune lymphoproliferation in mice and men. CD95-induced cell death
      may be defective in MS. We studied the association of CD95 and CD95L
      polymorphisms with MS in 221 unique patients representing 79% ascertainment in
      Olmsted County, MN, and 442 gender-, age- and ethnicity-matched controls. Being a
      homozygote for the G allele of CD95 5'(-670)*A-->G SNP (p=0.034; OR: 1.59, 95%
      CI: 1.06-2.38) and for the C allele of CD95 E7(74)*C-->T SNP (p=0.007; OR: 1.73,
      95% CI: 1.17-2.56) increased susceptibility to MS exclusively in women. There was
      strong but incomplete linkage disequilibrium between the two markers (p<0.001;
      D'=0.546). Homozygosity for 5'(-670)*A or E7(74)*C explained 28% of risk of MS in
      women but 0% of the risk in men in Olmsted County, MN. Our results agree with the
      previously published studies and highlight that the association of the
      polymorphisms is restricted to women with MS. We did not find an association
      between CD95L and susceptibility to MS nor CD95 or CD95L and age of onset,
      disease course and disease severity.

PMID- 14698860
TI  - Increase of matrix metalloproteinase-9 in peripheral blood of multiple sclerosis
      patients treated with high doses of methylprednisolone.
AB  - Matrix metalloproteinases (MMPs) are believed to play a role in the pathogenesis
      of multiple sclerosis (MS). As methylprednisolone is the treatment of choice for
      a relapse, we investigated the effect of methylprednisolone on blood levels of
      MMPs. Baseline TIMP-1 and MMP-2 levels were lower in MS patients than in healthy
      controls. MMP-9 levels tended to be elevated. During therapy, MMP-9 levels
      demonstrate a dose-dependent increase. No effect was noted on TIMP-1 and MMP-2
      levels. The short-lived increase of MMP-9 plasma levels may be at least in part
      due to an activation and an increase of granulocytes and monocytes by
      methylprednisolone.

PMID- 14698861
TI  - Impact of type-I-interferon on monocyte subsets and their differentiation to
      dendritic cells. An in vivo and ex vivo study in multiple sclerosis patients
      treated with interferon-beta.
AB  - In addition to CD14++ "classical" monocytes, human peripheral blood contains
      CD14+CD16+ "pro-inflammatory" monocytes, which may be influenced by IFNb
      treatment. By fluorescence activated cell sorting (FACS) analysis, 94 multiple
      sclerosis (MS) patients revealed normal absolute and relative numbers of both
      monocyte populations (71 untreated, 23 IFNb-treated). In IFNb-treated patients,
      CD14+CD16+ monocytes consistently expressed higher CD14, confirmed in 16 patients
      analyzed longitudinally. Ex vivo, CD1a+CD14+ dendritic cells (DC) were
      efficiently differentiated from peripheral blood cells from controls and
      untreated patients, but at considerably reduced efficiency in IFNb-treated
      patients. Addition of IFNb to the medium further reduced the induction of
      CD1a+CD14+ cells.IFNb induces a novel immunophenotypic shift in pro-inflammatory
      monocytes, which appears to be related to reduced formation of dendritic cell
      precursors.

PMID- 14698862
TI  - Cyclophosphamide modulates CD4+ T cells into a T helper type 2 phenotype and
      reverses increased IFN-gamma production of CD8+ T cells in secondary progressive
      multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system considered to be mediated by T helper type-1 cells. Several agents have
      been found to modify the disease course of MS, including interferon-beta1 (IFN
      beta1), glatiramer acetate mitoxantrone. We have employed pulse therapy with
      cyclophosphamide in a selected group of patients with actively progressive
      disease. Chemokine receptors have been found to differentiate between polarized T
      helper type-1 (Th1) and type-2 (Th2) lymphocytes. The chemokine receptors CCR5
      and CXCR3 are expressed primarily on Th1 cells and CCR3, CCR4 and CCR8 on Th2
      cells. Previous studies of the expression of chemokine receptors in MS have shown
      that active MS plaques are infiltrated by CCR5(+) and CXCR3(+) T cells. Some of
      these T cells may express both CCR5 and CXCR3. These T cells are major producers
      of IFN-gamma, which worsens the clinical condition of patients with MS. We
      previously found that patients with MS had a high proportion of CXCR3(+) T cells
      and that those with chronic progressive MS had a high proportion of CCR5(+) T
      cells in their peripheral blood. We report here that in patients with secondary
      progressive MS, cyclophosphamide induces a marked increase in the percentage of
      CCR4(+) T cells that produce high levels of IL-4 and reverses the increase in the
      percentages of IFN-gamma-producing CCR5(+) and CXCR3(+) CD8(+) T cells.
      Furthermore, therapy with cyclophosphamide increases IL-4-producing CD4(+) T
      cells and reverses the increase in IFN-gamma-producing CD8(+) T cells. Our study
      shows that cyclophosphamide has immunomodulatory properties besides its
      suppressive effects, and that chemokine receptors can be important tools both for
      understanding the immune dysregulation in MS and for monitoring response to
      therapy.

PMID- 14698863
TI  - Altered levels of nerve growth factor in the thymus of subjects with myasthenia
      gravis.
AB  - We have previously reported that nerve growth factor (NGF), a polypeptide known
      for its neurotrophic activities, is also involved in the differentiation and
      survival of immune cells, and that NGF and its high-affinity receptor are present
      in the thymus. We here demonstrate that the thymus of humans affected by
      myasthenia gravis (MG) contains significant concentrations of NGF. These
      observations support our hypothesis of a role for NGF in the thymus and suggest
      that the changes observed in the thymus of subject with MG may have functional
      significance.

PMID- 14698864
TI  - Induction of beta-chemokine secretion by human brain microvessel endothelial
      cells via CD40/CD40L interactions.
AB  - beta-chemokines play an important role during the course of central nervous
      system (CNS) inflammation. Using primary cultures of human cerebral microvascular
      endothelial cells, we detected increased monocyte chemoattractant protein-1 (MCP
      1) and regulated upon activation normal T cell expressed and secreted (RANTES)
      production following incubation with soluble CD40L. These results suggest a
      potential mechanism by which activated CD40L positive T cells may enhance beta
      chemokine expression and thus influence the recruitment of mononuclear cells
      across the human blood-brain barrier.

PMID- 14698865
TI  - Dysregulation of IL-10 and IL-12p40 in secondary progressive multiple sclerosis.
AB  - Multiple sclerosis (MS) is a putative T helper 1 (Th-1) mediated inflammatory
      disorder of the central nervous system, and levels of pro-inflammatory and anti
      inflammatory cytokines have been found to correlate with changes in MS relapses.
      However, it is unclear if cytokine profiles differ between relapsing-remitting
      (RRMS) versus secondary progressive (SPMS) disease stages. Cytokine production
      (IL-2, IL-4, IL-5, IL-10, IL-12p40, TNF-alpha, and IFN-gamma) was assessed by
      cytometric bead array (CBA) and intracellular cytokine staining from alphaCD3
      antibody and mitogen stimulated peripheral blood mononuclear cells (PBMCs) from
      female RRMS and SPMS patients, and healthy controls. Significantly increased
      production of IL-12p40 and decreased production of IL-10 were observed in SPMS
      patients. Differences in immune responsiveness in RRMS and SPMS are important in
      the understanding of the evolution of the immunopathogenesis of the disease and
      for the development of disease type specific treatments.

PMID- 14698868
TI  - Noninvasive monitoring of DNAPL migration through a saturated porous medium using
      electrical impedance tomography.
AB  - Electrical impedance tomography (EIT) was used to monitor the movement of a
      fluorinated hydrocarbon dense nonaqueous phase liquid (DNAPL) through a saturated
      porous medium within a laboratory column. Impedance measurements were made using
      a horizontal plane of 12 electrodes positioned at regular intervals around the
      centre of the column. A 2D inversion algorithm, which incorporated the
      cylindrical geometry of the column, was used to reconstruct resistivity and phase
      images from the measured data. Differential time-lapse images of DNAPL movement
      past the plane of electrodes were generated by the cell-by-cell subtraction of
      resistivity and phase baseline models from those associated with the DNAPL
      release stage of the experiment. The DNAPL pulse was clearly delineated as
      resistive anomalies in the differential time-lapse resistivity images. The
      spatial extent of the resistive anomalies indicated that in addition to vertical
      migration, some lateral spreading of the DNAPL had occurred. Residual
      contamination could be detected after quasi-static conditions were reestablished.
      Residual DNAPL saturation was estimated from the resistivity model data by
      applying Archie's second equation.Despite significant measured phase changes due
      to DNAPL contamination, the differential phase images revealed only weak
      anomalies associated with DNAPL flow; these anomalies could be seen only in the
      initial stages of the experiment during peak flow through the plane of
      electrodes.

PMID- 14698869
TI  - Study on anisotropy of effective diffusion coefficient and activation energy for
      deuterated water in compacted sodium bentonite.
AB  - To quantify the effects of temperature on the diffusivity of deuterated water
      (HDO) in compacted sodium bentonite, through-diffusion experiments were conducted
      at elevated temperatures ranging from 298 to 333 K. Kunipia F (Na-montmorillonite
      content>98 wt.%; Kunimine Industries) was compacted to a dry density of 0.9 or
      1.35 Mg/m(3). As montmorillonite particles were oriented perpendicular to the
      direction of compaction, the anisotropy of diffusivity was investigated both
      parallel and normal to the preferred orientation of the montmorillonite. The
      effective diffusion coefficient D(e) of HDO was larger when the diffusional
      direction was parallel as opposed to normal to the preferred orientation for both
      dry densities. The magnitude of D(e) and the anisotropy for HDO were in good
      accordance with previously reported results for tritiated water at room
      temperature. Activation energies of D(e) were isotropic and increased with
      increasing dry density over the range of 19-25 kJ/mol. This relationship was
      considered to be due to both pore structure development and the high activation
      energy of water near the montmorillonite surface.

PMID- 14698870
TI  - DNAPL remediation with in situ chemical oxidation using potassium permanganate.
      Part I. Mineralogy of Mn oxide and its dissolution in organic acids.
AB  - Previous studies on in situ chemical oxidation of trichloroethylene (TCE) with
      potassium permanganate indicated that the solid reaction product, Mn oxide, could
      reduce the permeability of the porous medium and impact the success of dense non
      aqueous phase liquid (DNAPL) removal. In order to address the issue of
      permeability reduction caused by precipitation, this study investigated the
      mineralogy of Mn oxides and the possibilities of removing the solid precipitates
      by dissolution. The solid reaction product from the oxidation of TCE by
      permanganate is semi-amorphous potassium-rich birnessite, which has a layered
      mineral structure with an interlayer spacing of 7.3 A. The chemical formula is
      K(0.854)Mn(1.786)O(4).1.55H(2)O. It has a relatively small specific surface area
      at 23.6+/-0.82 m(2)/g. Its point of zero charge (pzc) was measured as 3.7+/-0.4.
      This birnessite is a relatively active species and could participate in various
      reactions with existing organic and inorganic matter. The dissolution kinetics of
      Mn oxide was evaluated in batch experiments using solutions of citric acid,
      oxalic acid, and ethylenediaminetetraacetic acid (EDTA). Initial dissolution
      rates were determined to be 0.126 mM/m(2)/h for citric acid, 1.35 mM/m(2)/h for
      oxalic acid, and 5.176 mM/m(2)/h for EDTA. These rates compare with 0.0025
      mM/m(2)/h for nitric acid at pH=2. Organic acids dissolve Mn oxide quickly.
      Reaction rates increase with acid concentration, as tested with citric acid. The
      dissolution mechanism likely involves proton and ligand-promoted dissolution and
      reductive dissolution. Citric and oxalic acid can induce ligand-promoted
      dissolution, while EDTA can induce ligand-promoted and reductive dissolutions. At
      low pH, proton-promoted dissolution seems to occur with all the acids tested, but
      this process is not dominant. Reductive dissolution appears to be the most
      effective process in dissolving the solid, followed by ligand-promoted
      dissolution. These experiments indicate the significant potential in using these
      organic acids to remove precipitates formed during the oxidation reaction.

PMID- 14698871
TI  - The use of laboratory-determined ion exchange parameters in the predictive
      modelling of field-scale major cation migration in groundwater over a 40-year
      period.
AB  - An attempt has been made to estimate quantitatively cation concentration changes
      as estuary water invades a Triassic Sandstone aquifer in northwest England.
      Cation exchange capacities and selectivity coefficients for Na(+), K(+), Ca(2+),
      and Mg(2+) were measured in the laboratory using standard techniques. Selectivity
      coefficients were also determined using a method involving optimized back
      calculation from flushing experiments, thus permitting better representation of
      field conditions; in all cases, the Gaines-Thomas/constant cation exchange
      capacity (CEC) model was found to be a reasonable, though not perfect, first
      description. The exchange parameters interpreted from the laboratory experiments
      were used in a one-dimensional reactive transport mixing cell model, and
      predictions compared with field pumping well data (Cl and hardness spanning a
      period of around 40 years, and full major ion analyses in approximately 1980).
      The concentration patterns predicted using Gaines-Thomas exchange with calcite
      equilibrium were similar to the observed patterns, but the concentrations of the
      divalent ions were significantly overestimated, as were 1980 sulphate
      concentrations, and 1980 alkalinity concentrations were underestimated. Including
      representation of sulphate reduction in the estuarine alluvium failed to
      replicate 1980 HCO(3) and pH values. However, by including partial CO(2)
      degassing following sulphate reduction, a process for which there is 34S and 18O
      evidence from a previous study, a good match for SO(4), HCO(3), and pH was
      attained. Using this modified estuary water and averaged values from the
      laboratory ion exchange parameter determinations, good predictions for the field
      cation data were obtained. It is concluded that the Gaines-Thomas/constant
      exchange capacity model with averaged parameter values can be used successfully
      in ion exchange predictions in this aquifer at a regional scale and over extended
      time scales, despite the numerous assumptions inherent in the approach; this has
      also been found to be the case in the few other published studies of regional ion
      exchanging flow.

PMID- 14698872
TI  - An analytical solution for estimating percolation rate by fitting temperature
      profiles in the vadose zone.
AB  - We present a simple analytical solution for one-dimensional steady heat transfer
      with convection and conduction through a multilayer system such as a vadose zone.
      We assume that each layer is homogeneous and has a constant thermal diffusivity.
      The mass/heat flow direction is perpendicular to the layers, and the mass flow
      rate is a constant. The analytical solution presented in this study also assumes
      constant known temperatures at the two boundaries of the system. Although the
      analytical solution gives the temperature as a function of a few parameters, we
      focus on the inverse application to estimate the percolation rate in a vadose
      zone. Example applications have shown that with reliable field observation data,
      the solution can be used to determine the percolation rate to high degree of
      accuracy (e.g., to mm/year). In some other cases, the solution may also be
      helpful in characterizing potential lateral flow along layer divides.

PMID- 14698873
TI  - Modelling the solute transport under nonequilibrium conditions on the basis of
      mass transfer equations.
AB  - A solute transport model that describes nonequilibrium adsorption in
      soil/groundwater systems by mass transfer equations for film and intraparticle
      diffusion is presented. The model is useful in cases where breakthrough curve
      spreading cannot be explained by dispersion only. To evaluate its validity, the
      model was applied to several data sets from column experiments. The validity was
      also proved by a comparison with an analytical solution for the limiting case of
      predominating dispersion. Furthermore, a sensitivity analysis was performed to
      illustrate the influence of different process and sorption parameters (pore water
      velocity, intraparticle mass transfer coefficient, isotherm nonlinearity) on the
      shape of the calculated breakthrough curves. The application of the proposed
      model is discussed in comparison to the widely used dispersed flow/local
      equilibrium model, and a relationship between both models, which is based on a
      lumped parameter approach, is shown.

PMID- 14698874
TI  - Bioremediation of chlorobenzene-contaminated ground water in an in situ reactor
      mediated by hydrogen peroxide.
AB  - New in situ reactive barrier technologies were tested nearby a local aquifer in
      Bitterfeld, Saxonia-Anhalt, Germany, which is polluted mainly by chlorobenzene
      (CB), in concentrations up to 450 microM. A reactor filled with original aquifer
      sediment was designed for the microbiological remediation of the ground water by
      indigenous bacterial communities. Two remediation variants were examined: (a) the
      degradation of CB under anoxic conditions in the presence of nitrate; (b) the
      degradation of CB under mixed electron acceptor conditions (oxygen+nitrate) using
      hydrogen peroxide as the oxygen-releasing compound. Under anoxic conditions, no
      definite degradation of CB was observed. Adding hydrogen peroxide (2.94 mM) and
      nitrate (2 mM) led to the disappearance of CB (ca. 150 microM) in the lower part
      of the reactor, accompanied by a strong increase of the number of cultivable
      aerobic CB degrading bacteria in reactor water and sediment samples, indicating
      that CB was degraded mainly by productive bacterial metabolism. Several aerobic
      CB degrading bacteria, mostly belonging to the genera Pseudomonas and
      Rhodococcus, were isolated from reactor water and sediments. In laboratory
      experiments with reactor water, oxygen was rapidly released by hydrogen peroxide,
      whereas biotic-induced decomposition reactions of hydrogen peroxide were almost
      four times faster than abiotic-induced decomposition reactions. A clear chemical
      degradation of CB mediated by hydrogen peroxide was not observed. CB was also
      completely degraded in the reactor after reducing the hydrogen peroxide
      concentration to 880 microM. The CB degradation completely collapsed after
      reducing the hydrogen peroxide concentration to 440 microM. In the following, the
      hydrogen peroxide concentrations were increased again (to 880 microM, 2.94 mM,
      and 880 microM, respectively), but the oxygen demand for CB degradation was
      higher than observed before, indicating a shift in the bacterial population.
      During the whole experiment, nitrate was uniformly reduced during the flow path
      in the reactor.

PMID- 14698875
TI  - A convergent strategy for the preparation of N-glycan core di-, tri-, and
      pentasaccharide thioaldoses for the site-specific glycosylation of peptides and
      proteins bearing free cysteines.
AB  - Mammalian glycoprotein biosynthesis produces heterogeneous ranges of proteins
      that possess the same peptide backbone but differ in the nature and site of
      glycosylation. This feature has frustrated efforts to develop therapeutic
      glycoproteins as well as the elucidation of biological functions of individual
      glycoforms. We have developed an attractive approach to well-defined glycoforms
      of glycoproteins by oxidative coupling of thioaldoses to cysteine-containing
      peptides and proteins to give disulfide-linked neoglycoconjugates. To this end,
      the chemical synthesis di-, tri-, and pentasaccharide N-glycan thioaldoses was
      undertaken. A convergent approach was used for the preparation of the
      pentasaccharide containing a 'synthetically difficult' beta-mannoside linkage.
      This linkage was installed by forming initially the corresponding beta-glucoside
      containing pentasaccharide, followed by inversion of configuration at C-2. This
      approach exploited a levulonyl ester at C-2 of a glucosyl donor, which directed
      the coupling to give the beta-glucoside exclusively and could be removed
      selectively using hydrazine acetate without affecting other base-labile
      functionalities. The resulting alcohol was converted into a triflate, which was
      displaced by tri-n-butylammonium acetate to give a beta-mannosidic linkage. The
      trisaccharide N-glycan was prepared in a similar manner. Thioaldoses were
      prepared by displacing the peracetylated alpha-glycosyl chlorides with
      thioacetate to give the peracetylated beta-thioacetates, which upon
      saponification gave the desired compounds. The incubation of molar excesses of
      chitobiose thioaldose with cysteine-containing glutathione and BSA resulted in
      the site-specific formation of a disulfide-linked neoglycopeptide and
      neoglycoprotein, respectively.

PMID- 14698876
TI  - Structure of the O-polysaccharide of Providencia stuartii O4 containing 4-(N
      acetyl-L-aspart-4-yl)amino-4,6-dideoxy-D-glucose.
AB  - The O-polysaccharide of Providencia stuartii O4 was obtained by mild acid
      degradation of the lipopolysaccharide, and the following structure of the
      pentasaccharide repeating unit was established: [structure: see text] where D
      Qui4N(L-AspAc) is 4-(N-acetyl-L-aspart-4-yl)amino-4,6-dideoxy-D-glucose, which
      has not been hitherto found in bacterial polysaccharides. Structural studies were
      performed using sugar and methylation analyses, Smith degradation and NMR
      spectroscopy, including conventional 2D 1H,1H COSY, TOCSY, NOESY and 1H,13C HSQC
      experiments as well as COSY and NOESY experiments run in an H(2)O-D(2)O mixture
      to reveal correlations for NH protons.

PMID- 14698877
TI  - Structural investigation of hemicellulosic polysaccharides from Argania spinosa:
      characterisation of a novel xyloglucan motif.
AB  - Hemicellulose polymers were isolated from Argania spinosa leaf cell walls by
      sequential extractions with alkali. The structure of the two main polymers, xylan
      and xyloglucan, was investigated by enzyme degradation with specific
      endoglycosidases followed by analysis of the resulting fragments by high
      performance anion exchange chromatography (HPAEC) and matrix-assisted laser
      desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS). The
      results show that A. spinosa xylan is composed of a beta-(1-->4)-linked-D
      xylopyranose backbone substituted with 4-O-methyl-D-glucuronic acid residues.
      Xyloglucan oligosaccharide subunits were generated by treatment with an endo-(1-
      >4)-beta-D-glucanase of the xyloglucan-rich hemicellulosic fractions. MALDI-TOF
      mass spectra and HPAE-PAD chromatography of the pool of endoglucanase-generated
      xyloglucan oligomers indicated that A. spinosa cell wall contains a XXXG-type
      xyloglucan. In addition to XXXG, XXFG, XLXG/XXLG, XLFG fragments previously
      characterised in various plants, a second group of XXXG-type fragments was
      detected. The primary structure of the major subunit was determined by a
      combination of sugar analysis, methylation analysis, post-source decay (PSD)
      fragment analysis of MALDI-TOF MS and 1H NMR spectroscopy. This fragment, termed
      XUFG, contains a novel beta-D-Xylp-(1-->2)-alpha-D-Xylp side chain linked to C-6
      of the second glucose unit from the nonreducing end of the cellotetraose
      sequence.

PMID- 14698878
TI  - Physicochemical studies of pectin/poly-L-lysine gelation.
AB  - The effect of poly-L-lysine concentration and degree of polymerisation on the
      gelation of pectins differing in charge density and distribution was examined,
      through the determination of gel stiffness, swelling behaviour and the binding of
      poly-L-lysine to the gel network. Poly-L-lysine acts as a crosslinker of
      concentrated pectin solutions, with its effectiveness showing dependencies on pH
      and charge distribution on the pectin. Neutralisation of the anionic charge on
      the pectin with the polycationic peptide leads to gel opacity and eventually
      network collapse.

PMID- 14698879
TI  - The composition of 2-keto aldoses in organic solvents as determined by NMR
      spectroscopy.
AB  - The composition of the 2-keto aldoses D-glucosone (1), 6-deoxy-D-glucosone (2), D
      allosone (3), and D-galactosone (4) in organic solvents has been determined using
      NMR spectroscopy. Whereas these keto aldoses form mixtures with up to 15
      different isomers in water, the number of forms is significantly decreased in
      organic solvents. Equilibrium mixtures of 1, 2, and 4 in Me(2)SO, DMF, and
      pyridine consist to 70-90% of the prevailing alpha-1,5-pyranose form. Two
      bicyclic forms with a proportion of 80% are the main isomers of 3 in pyridine.
      Generally, forms with non-hydrated keto functions prevail in non-aqueous
      solutions.

PMID- 14698880
TI  - Neutral, acidic, and basic derivatives of anthranilamide that confer different
      formal charge to reducing oligosaccharides.
AB  - To facilitate the use of oligosaccharides as analytical tools in biological
      studies, we have designed, synthesized, and conjugated to maltosaccharides a
      novel series of homologous small fluorescent moieties that differ in formal
      charge. These moieties are amide derivatives of anthranilic acid: uncharged N-(2
      aminobenzoyl)glycinamide (ABGlyAmide; 2), acidic N,N-dimethyl-N(')-(2
      aminobenzoyl)ethylenediamine (ABGlyDIMED; 3), and basic N-(2-aminobenzoyl)glycine
      (ABGly; 1). Routes for synthesis and optimal reaction conditions for
      glycoconjugation by conventional reductive amination are presented, as is the
      compatibility of these adducts with common analytical and preparative
      chromatographic methods, including RP-HPLC and HPAEC-PAD. These novel anthranilic
      acid derivatives confer both fluorescence and defined charge to oligosaccharides,
      and so enhance the repertoire of chromatographic and analytical methods for which
      anthranilic acid can be used. Furthermore, because glucosaccharides have rigid
      solution structure, these small fluorescent adducts with different formal charge
      are ideal tools for molecular sizing studies of membrane pores.

PMID- 14698881
TI  - Structure of the inclusion complexes of heptakis(2,3,6-tri-O-methyl)-beta
      cyclodextrin with indole-3-butyric acid and 2,4-dichlorophenoxyacetic acid.
AB  - The crystal structures of the complexes of heptakis(2,3,6-tri-O-methyl)-beta
      cyclodextrin with indole-3-butyric acid and with 2,4-dichlorophenoxyacetic acid
      were studied by X-ray diffraction. The complexes crystallize in the monoclinic
      P2(1) space group. The host molecules are elliptically puckered and stacked along
      the a crystal axis, in a head-to-tail fashion, forming columns. One primary
      methoxy group of the host molecule of the complex with indole-3-butyric acid has
      the unusual trans-gauche conformation for permethylated CDs. All the secondary O
      3-CH(3) methoxy groups, some secondary O-2-CH(3) and some primary methoxy groups
      pointing inwards the cavity enclose the indole or the 2,4-dichlorophenoxy
      moieties of the guest molecules inside the cavity, while the chains of the guests
      protrude between two adjacent host molecules of the columns. The mean planes of
      the indole and 2,4-dichlorophenoxy moieties of the guests are nearly
      perpendicular to the mean planes of the elliptical heptagons defined by the O-4n
      atoms of the hosts. The carboxyl group of the guests form hydrogen bonds with
      oxygen atoms of the host molecules or with the water molecules found in the space
      between the complexes of the same column.

PMID- 14698883
TI  - Rod-like architecture and helicity of the poly(C)/schizophyllan complex observed
      by AFM and SEM.
AB  - Microscopic studies of the complex between poly(C) and schizophyllan (SPG),
      employing both AFM and SEM, revealed that the complex takes the same rod-like
      architecture on the mica surface as those of the renatured SPG and the original
      triple helix of SPG, indicating that the complex also has a helical structure.
      The SEM observations showed the helical pattern on the rod surface, only when the
      sample was metal shadowed. The pitch evaluated from the image is comparable with
      that obtained from crystallographic data. The ability to visualize the helical
      structure can be explained from the hypothesis that the platinum grains may
      assemble on the sample using the molecular surface of the SPG (or complex) as the
      template.

PMID- 14698882
TI  - Evaluation of newly synthesized and commercially available charged
      cyclomaltooligosaccharides (cyclodextrins) for capillary electrokinetic
      chromatography.
AB  - A highly new charged cyclodextrin (CD) derivatives, (6-O-carboxymethyl-2,3-di-O
      methyl)cyclomaltoheptaoses (CDM-beta-CDs), was synthesized and characterized as
      anionic reagents for capillary electrophoresis (CE) in an electrokinetic
      chromatography mode of separation. Substitution with dimethyl groups at the
      secondary hydroxyl sites of the CD is aimed at influencing the magnitude and
      selectivity of analyte-CD interactions, while substitution by carboxymethyl
      groups at the primary hydroxyl sites provides for high charge and electrophoretic
      mobility. Full regioselective methylation at the secondary hydroxyl sites was
      achieved in this work, while substitution at the primary hydroxyl sites generated
      a mixture of multiply charged products. The separation performance of CDM-beta-CD
      was evaluated using a variety of analyte mixtures. The results obtained from
      commercially available negatively charged cyclodextrins, heptakis(2,3-di-O-methyl
      6-O-sulfo)cyclomaltoheptaose (HDMS-beta-CD) and O
      (carboxymethyl)cyclomaltoheptaose (CM-beta-CD) with an average degree of
      substitution one (DS 1), were compared to CDM-beta-CD using a sample composed of
      eight positional isomers of dihydroxynaphthalene. Four hydroxylated
      polychlorobiphenyl derivatives, a group of chiral and isomeric catchecins, and
      chiral binaphthyl compounds were also separated with CDM-beta-CD. The effect of
      adding neutral beta-cyclodextrin (beta-CD) into the running buffer containing
      charged cyclodextrins was investigated and provided evidence of significant inter
      CD interactions. Under certain running buffer conditions, the charged
      cyclodextrins also appear to adsorb to the capillary walls to various degrees.

PMID- 14698884
TI  - Saturation transfer difference NMR and computational modeling of a sialoadhesin
      sialyl lactose complex.
AB  - The siglecs are a family of I-type lectins binding to sialic acids on the cell
      surface. Sialoadhesin (siglec-1) is expressed at much higher levels in
      inflammatory macrophages and specifically binds to alpha-2,3-sialylated N-acetyl
      lactosamine residues of glycan chains. The terminal disaccharide alpha-D-Neu5Ac
      (2-->3)-beta-D-Gal is thought to be the main epitope recognized by sialoadhesin.
      To understand the basis of this biological recognition reaction we combined NMR
      experiments with a molecular modeling study. We employed saturation transfer
      difference (STD) NMR experiments to characterize the binding epitope of alpha-2,3
      sialylated lactose, alpha-D-Neu5Ac-(2-->3)-beta-D-Gal-(1-->4)-D-Glc 1 to
      sialoadhesin at atomic resolution. The experimental results were compared to a
      computational docking model and to X-ray data of a complex of sialyl lactose and
      sialoadhesin. The data reveal that sialoadhesin mainly recognizes the N-acetyl
      neuraminic acid and a small part of the galactose moiety of 1. The crystal
      structure of a complex of sialoadhesin with sialyl lactose 1 was used as a basis
      for a modeling study using the FlexiDock algorithm. The model generated was very
      similar to the original crystal structure. Therefore, the X-ray data were used to
      predict theoretical STD values utilizing the CORCEMA-STD protocol. The good
      agreement between experimental and theoretical STD values indicates that a
      combined modeling/STD NMR approach yields a reliable structural model for the
      complex of sialoadhesin with alpha-D-Neu5Ac-(2-->3)-beta-D-Gal-(1-->4)-D-Glc 1 in
      aqueous solution.

PMID- 14698885
TI  - QSPR models for various physical properties of carbohydrates based on molecular
      mechanics and quantum chemical calculations.
AB  - Quantitative Structure-Property Relationships (QSPR) have been developed for a
      series of monosaccharides, including the physical properties of partial molar
      heat capacity, heat of solution, melting point, heat of fusion, glass-transition
      temperature, and solid state density. The models were based on molecular
      descriptors obtained from molecular mechanics and quantum chemical calculations,
      combined with other types of descriptors. Saccharides exhibit a large degree of
      conformational flexibility, therefore a methodology for selecting the
      energetically most favorable conformers has been developed, and was used for the
      development of the QSPR models. In most cases good correlations were obtained for
      monosaccharides. For five of the properties predictions were made for
      disaccharides, and the predicted values for the partial molar heat capacities
      were in excellent agreement with experimental values.

PMID- 14698886
TI  - Molecular dynamics simulation of a decasaccharide fragment of heparin in aqueous
      solution.
AB  - Molecular dynamics (MD) simulations on heparin-water-sodium systems were carried
      out in order to establish a simulation protocol able to represent heparin
      solution conformation under physiological conditions. Atomic charges suitable for
      heparin oligosaccharides were obtained from ab initio quantum-mechanical
      computations, at the 6-31G(**) level. The GROMACS forcefield, the SPC, and SPC/E
      water models were employed. Also heparin was simulated with IdoA residues in
      1C(4) or 2S(0) conformational states. The results of the performed MD simulations
      are in agreement with the available experimental data, suggesting that this
      approach can be applied for the study of heparin interactions with its target
      proteins and thus play a role in the development of new antithrombotic agents.

PMID- 14698887
TI  - Fractional and physico-chemical characterization of hemicelluloses from
      ultrasonic irradiated sugarcane bagasse.
AB  - The present study was undertaken to investigate the extractability of the
      hemicelluloses from bagasse obtained by ultrasound-assisted extraction methods.
      The results showed that the ultrasonic treatment and sequential extractions with
      alkali and alkaline peroxide under the conditions given led to a release of over
      90% of the original hemicelluloses and lignin. This fact as well as the sugar
      composition and structural features of the isolated seven hemicellulosic
      fractions indicated that ultrasonication attacked the integrity of cell walls,
      cleaved the ether linkages between lignin and hemicelluloses, and increased
      accessibility and extractability of the hemicelluloses. Increasing alkali
      concentration from 0.5 to 2M and alkaline peroxide percentage from 0.5% to 3.0%
      resulted in degradation of hemicellulosic backbone as shown by a decrease in
      their molecular weights from 43,580 to 14,470 and 30,180 to 18,130gmol(-1),
      respectively. However, there were no significant differences in the structural
      features of the seven sequential alkali- or alkaline peroxide-soluble
      hemicellulosic fractions, which are composed mainly of L-arabino-(4-O-methyl-D
      glucurono)-D-xylans. Ferulic and p-coumaric acids were found to be chemically
      linked with hemicelluloses.

PMID- 14698888
TI  - NMR structural determination of dissolved O-acetylated galactoglucomannan
      isolated from spruce thermomechanical pulp.
AB  - Water-soluble O-acetylated galactoglucomannan (GGM) isolated from spruce
      thermomechanical pulp (TMP) by hot-water extraction was characterized by 1D and
      2D (homo- and heteronuclear) NMR analysis. The backbone was found to consist of
      (1-->4)-linked mannopyranosyl and glucopyranosyl units in a ratio of 10:1.9-2.6.
      The mannopyranosyl units were acetylated at C-2 and C-3 with a degree of
      acetylation around 0.28-0.37 as determined by NMR. A slightly larger amount of 2
      O-acetylated mannopyranosyl was detected when compared to the 3-O-acetylated
      component. Approximately every 10th mannopyranosyl unit was substituted at C-6 by
      a single alpha-galactopyranosyl unit. Fine structure determination based on
      sequence-specific chemical shift variations showed that the distribution of
      glycosyl residues is random. Small amounts of other minor polysaccharide species
      including xylans and galactans could also be identified by NMR.

PMID- 14698889
TI  - Synthesis and antimicrobial activity of a water-soluble chitosan derivative with
      a fiber-reactive group.
AB  - A novel fiber-reactive chitosan derivative was synthesized in two steps from a
      chitosan of low molecular weight and low degree of acetylation. First, a water
      soluble chitosan derivative, N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan
      chloride (HTCC), was prepared by introducing quaternary ammonium salt groups on
      the amino groups of chitosan. This derivative was further modified by introducing
      functional (acrylamidomethyl) groups, which can form covalent bonds with
      cellulose under alkaline conditions, on the primary alcohol groups (C-6) of the
      chitosan backbone. The fiber-reactive chitosan derivative, O-acrylamidomethyl
      HTCC (NMA-HTCC), showed complete bacterial reduction within 20 min at the
      concentration of 10ppm, when contacted with Staphylococcus aureus and Escherichia
      coli (1.5-2.5 x 10(5) colony forming units per milliliter [CFU/mL]).

PMID- 14698890
TI  - Structure of the O-polysaccharide of Citrobacter youngae O1 containing an alpha-D
      ribofuranosyl group.
AB  - The lipopolysaccharide of Citrobacter youngae O1, strain PCM 1492 was degraded
      with acid or alkali under mild conditions, and the resultant polysaccharide was
      isolated by GPC and studied by sugar and methylation analyses and 1H and 13C NMR
      spectroscopies, including 2D COSY, TOCSY, NOESY and 1H, 13C HSQC experiments. The
      following structure of the branched tetrasaccharide repeating unit of the O
      polysaccharide was established: [structure: see text] where substitution with the
      alpha-D-Ribf group is nonstoichiometric. This group occurs rarely in bacterial
      polysaccharides and is easily cleaved under mild acidic conditions. Studies with
      polyclonal rabbit antisera against whole cells of C. youngae PCM 1492 and PCM
      1506 showed the serological identity of the lipopolysaccharides of C. youngae PCM
      1492, PCM 1493 and PCM 1506, which are classified in serogroup O1.

PMID- 14698891
TI  - Chemical components and molecular mass of six polysaccharides isolated from the
      sclerotium of Poria cocos.
AB  - Six polysaccharides were extracted sequentially from the fresh sclerotium of
      Poria cocos cultivated in China using 0.9% NaCl (PCS1), hot water (PCS2), 0.5M
      NaOH (PCS3-I and PCS3-II), and 88% formic acid (PCS4-I and PCS4-II). Their
      chemical and physical characteristics were determined using infrared spectroscopy
      (IR), gas chromatography (GC), GC-MS methylation analysis, 13C NMR spectroscopy,
      elementary analysis (EA), protein analysis, size exclusion chromatography
      combined with laser light scattering (SEC-LLS), light scattering (LS), and
      viscometry. The results indicated that the polysaccharides PCS1, PCS2, and PCS3-I
      were heteropolysaccharides containing D-glucose, D-galactose, D-mannose, D
      fucose, and D-xylose; the predominant monosaccharide was D-glucose except for
      PCS1 where it was D-galactose. PCS3-II, the main component of the sclerotium of
      P. cocos, was a linear (1-->3)-beta-D-glucan of high purity. PCS4-I consisted of
      (1-->3)-beta-D-glucan with some beta-(1-->6) linked branches. PCS4-II was mainly
      composed of (1-->3)-beta-D-glucan containing some glucose branches. The M(w)
      values of the six polysaccharides PCS1, PCS2, PCS3-I, PCS4-I in 0.2M NaCl aqueous
      solution, PCS3-II, and PCS4-II in dimethyl sulfoxide (Me(2)SO) were determined to
      be 11.6 x 10(4), 20.8 x 10(4), 17.1 x 10(4), 9.1 x 10(4), 12.3 x 10(4), and 21.1
      x 10(4), respectively. The six polysaccharides in aqueous solution or Me(2)SO
      exist as flexible chains.

PMID- 14698893
TI  - An expeditious preparation of various sulfoforms of the disaccharide beta-D-Galp
      (1-->3)-D-Galp, a partial structure of the linkage region of proteoglycans, as
      their 4-methoxyphenyl beta-D-glycosides.
AB  - An expeditious preparation of various sulfoforms of the disaccharide 4
      methoxyphenyl O-(beta-D-galactopyranosyl)-(1-->3)-beta-D-galactopyranoside,
      namely the 4(I)- and 6(I)-sulfate, the 4(II)- and 6(II)-sulfate, and the
      6(I),6(II)-disulfate derivatives, is reported for the first time. These molecules
      will be useful for the study of the early steps of the biosynthesis and sorting
      of proteoglycans. All target compounds were readily obtained from the common key
      intermediate 4-methoxyphenyl O-(2,3-di-O-benzoyl-4,6-di-O-levulinoyl-beta-D
      galactopyranosyl)-(1-->3)-2-O-benzoyl-4,6-O-benzylidene-beta-D-galactopyranoside,
      easily prepared from the common starting material 4-methoxyphenyl 4,6-O
      benzylidene-beta-D-galactopyranoside. Noticeable is the possible preparation of
      the different 6-O-sulfonated species through a one-pot procedure starting from a
      tetrol precursor.

PMID- 14698892
TI  - The structure of the agaran sulfate from Acanthophora spicifera (Rhodomelaceae,
      Ceramiales) and its antiviral activity. Relation between structure and antiviral
      activity in agarans.
AB  - The sulfated agaran isolated by water extraction from the red seaweed,
      Acanthophora spicifera (Rhodomelaceae, Ceramiales), is made up of A-units highly
      substituted with sulfate groups on C-2 (28-30%), sulfates on C-2 and 4,6-O-(1'
      carboxyethylidene) groups (9-15%), and only the C-2 sulfate groups (5-8%) with
      small amounts of C-6 sulfate, 6-O-methyl, and nonsubstituted residues. B-units
      are formed mainly by 3,6-anhydro-alpha-L-galactose (15-16%) and its precursor,
      alpha-L-galactose 6-sulfate (10-17%), together with lesser amounts of 3,6-anhydro
      alpha-L-galactose 2-sulfate, alpha-L-galactose 2,6-disulfate, alpha-L-galactose
      2,3,6-tri-sulfate, alpha-L-galactose 2,6-disulfate 3-xylose, 2-O-methyl-alpha-L
      galactose, and unsubstituted alpha-L-galactose. Small, but significant quantities
      of beta-D-xylose were found in all the fractions, together with small amounts to
      traces of D-glucose. Some of the fractions have high antiviral activity. Attempts
      to correlate structure and antiviral activity in agarans are presented.

PMID- 14698894
TI  - Synthesis of (+)-(2R,3S,4R)-2,3,4-trihydroxycyclohexanone from D-glucose.
AB  - We have described the synthesis of (+)-(2R,3S,4R)-2,3,4-trihydroxycyclohexanone
      by the reduction of a keto-conduritol derivative, the latter being prepared in
      five steps from (-)-(2S,3R,4S,5S)-2,3,4-tribenzyloxy-5-hydroxycyclohexanone,
      which is in turn readily synthesized from D-glucose.

PMID- 14698895
TI  - Synthesis of N-(fluoren-9-ylmethoxycarbonyl)glycopyranosylamine uronic acids.
AB  - The synthesis of 10 N-(fluoren-9-ylmethoxycarbonyl)glycopyranosylamine uronic
      acids that are amenable to solid-phase synthesis is described. The general
      synthetic strategy involves initial incorporation of the protected amine,
      followed by selective TEMPO oxidation of C-6 hydroxyl groups to give the
      corresponding Fmoc-protected sugar amino acids. Amine incorporation may be
      accomplished from aminolysis of the free sugar or from glycosyl azide reduction.
      The reactions can be carried out on multigram scale, providing access to unique
      monomer units for future incorporation into combinatorial library syntheses.

PMID- 14698896
TI  - Synthesis of mannose-containing analogues of (1-->6)-branched (1-->3)
      glucohexaose.
AB  - Coupling of the trisaccharide acceptor 2,4,6-tri-O-acetyl-beta-D-glucopyranosyl
      (1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-5-O-acetyl-1,2-O
      isopropylidene-alpha-D-glucofuranose (2) with the trisaccharide donor 2,3,4,6
      tetra-O-benzoyl-alpha-D-annopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D
      glucopyranosyl-(1-->6)]-2,4-di-O-acetyl-alpha-D-glucopyranosyl
      trichloroacetimidate (1) gave an alpha-linked hexasaccharide 3, while coupling of
      2 with the trisaccharide donor 2,3,4,6-tetra-O-benzoyl-alpha-D-mannopyranosyl-(1-
      >3)-[2,3,4,6-tetra-O-benzoyl-alpha-D-mannopyranosyl-(1-->6)]-2,4-di-O-acetyl
      alpha-D-glucopyranosyl trichloroacetimidate (7) produced alpha- 8 and beta-linked
      12 hexasaccharides in a ratio of 3:2. Deprotection of 3, 8, and 12 afforded the
      analogues of the immunomodulator beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-alpha
      D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-D-Glcp (A).

PMID- 14698897
TI  - Synthesis and evaluation of a mechanism-based inhibitor of KDO8P synthase.
AB  - The enzyme 3-deoxy-D-manno-2-octulosonate-8-phosphate (KDO8P) synthase catalyzes
      the condensation reaction between phosphoenolpyruvate (PEP) and D-arabinose 5
      phosphate (A5P) to produce KDO8P and inorganic phosphate. In attempts to
      investigate the lack of antibacterial activity of the most potent inhibitor of
      KDO8P synthase, the amino phosphonophosphate 3, we have synthesized its
      hydrolytically stable isosteric phosphonate analogue 4 and tested it as an
      inhibitor of the enzyme. The synthesis of 4 was accomplished in a one step
      procedure by employing the direct reductive amination in aqueous media between
      unprotected sugar phosphonate and glyphosate. The analogue 4 proved to be a
      competitive inhibitor of KDO8P synthase with respect to both substrates A5P and
      PEP binding. In vitro antibacterial tests against a series of different Gram
      negative organisms establish that both inhibitors (3 and 4) lack antibacterial
      activity probably due to their reduced ability to penetrate the bacterial cell
      membrane.

PMID- 14698898
TI  - Synthesis of the pentasaccharide repeating unit of the major O-antigen component
      from Pseudomonas syringae pv. ribicola NVPPB 1010.
AB  - The synthesis of the repeating unit of the major O-antigen component from
      Pseudomonas syringae pv. ribicola NVPPB 1010 is reported. The strategy used was
      based on the successive coupling of a trisaccharide rhamnosyl
      trichloroacetimidate with a rhamnosyl acceptor with a free hydroxyl group on C-2.
      The pentasaccharide was then obtained by coupling with a N-Troc-tri-O-acetyl
      glucosamine trichloroacetimidate. The synthesis allowed the oligomerisation of
      the repeating unit.

PMID- 14698899
TI  - Synthesis of a novel class of sulfonium ions as potential inhibitors of UDP
      galactopyranose mutase.
AB  - Two sulfonium salts of 1,4-anhydro-4-thio-D-galactitol, with structures related
      to the known sulfonium salt glycosidase inhibitor, salacinol, have been
      synthesized as potential inhibitors of UDP-galactopyranose mutase. The synthetic
      strategy relies on the alkylation reaction of 1,4-anhydro-2,3,5,6-tetra-O-benzyl
      4-thio-D-galactitol at the sulfur atom with 2,4-O-benzylidene-D- or -L-erythritol
      1,3-cyclic sulfate. In each case, the reaction proceeded stereoselectively to
      yield only one stereoisomer at the stereogenic sulfur atom. The effect of the
      polar solvent, 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), in promoting high
      yielding reactions is highlighted. The target compounds are then obtained by
      hydrogenolysis.

PMID- 14698900
TI  - Structure and cross-reactivity of the O-antigen of Providencia stuartii O18
      containing 3-acetamido-3,6-dideoxy-D-glucose.
AB  - The O-polysaccharide (O-antigen) of Providencia stuartii O18 was obtained by mild
      acid degradation of the lipopolysaccharide and studied by chemical methods and
      NMR spectroscopy, including 2D 1H,1H COSY, TOCSY, NOESY and 1H,13C HSQC
      experiments. The following structure of the tetrasaccharide repeating unit of the
      polysaccharide was established: [structure: see text] where Qui3NAc is 3
      acetamido-3,6-dideoxyglucose. Anti-P. stuartii O18 serum cross-reacted with the O
      antigen of Proteus genomospecies 4, which could be accounted for the marked
      structural similarities of the main chain.

PMID- 14698901
TI  - Structure of the O-polysaccharide of Providencia alcalifaciens O19.
AB  - Studies of the O-polysaccharide chain of the lipopolysaccharide (O-antigen) of
      Providencia alcalifaciens O19 by sugar and methylation analyses along with NMR
      spectroscopy, including 2D 1H,1H COSY, TOCSY, NOESY and 1H,13C HSQC experiments,
      showed that the pentasaccharide repeating unit of the polysaccharide has the
      following structure: [structure: see text] where Fuc3NAc is 3-acetamido-3,6
      dideoxygalactose. The unique structure of the O-antigen and serological data are
      in consistence with classification of this bacterium in a separate Providencia
      serogroup.

PMID- 14698902
TI  - Characterization of a beta-D-(1-->3)-glucan from the marine diatom Chaetoceros
      mulleri by high-resolution magic-angle spinning NMR spectroscopy on whole algal
      cells.
AB  - High-resolution magic-angle spinning (hr-MAS) NMR spectroscopy was used to record
      NMR spectra of a cell paste from the marine diatom Chaetoceros mulleri. This gave
      information on a cellular storage polysaccharide identified as a beta-D-(1-->3)
      linked glucan, using hr-MAS one-dimensional 1H and 13C, two-dimensional 1H,1H
      COSY and 13C,1H-correlation spectroscopy. The same structural information was
      deduced from the liquid state NMR data on the glucan extracted from C. mulleri.
      The extracted glucan proved to be a beta-D-(1-->3)-linked glucan with a degree of
      polymerization of 19 and a degree of beta-D-(1-->6) branching of 0.005. The hr
      MAS spectrum of the diatom showed several nonglucan resonances in the
      carbohydrate region of the NMR spectrum (60-103 ppm) that were shown to be
      noncarbohydrate resonances by means of two-dimensional 13C,1H- and 1H,1H
      correlated NMR data.

PMID- 14698903
TI  - An efficient chemoenzymatic route to methyl 4-O-benzyl-2,3-anhydro-beta-D
      lyxopyranoside from methyl beta-D-xylopyranoside.
AB  - Methyl 4-O-benzyl-2,3-anhydro-beta-D-lyxopyranoside, an intermediate for the
      preparation of methyl beta-D-xylopyranoside derivatives modified at C-2, was
      obtained in five steps in 58% yield. The synthetic sequence starts from methyl
      beta-D-xylopyranoside through two main steps involving regioselective enzymatic
      acetylation and deacetylation catalyzed by lipase PS.

PMID- 14698904
TI  - Conversion of diacetyl-C-(beta-D-glucopyranosyl)phloroglucinol to spiroketal
      compounds.
AB  - Diacetyl-C-(beta-D-glucopyranosyl)phloroglucinol was converted by refluxing in
      water to spiro(benzofuran-[2H]furan) a new compound, along with spiro(benzofuran
      [2H]pyran). The stereochemistry of the quaternary carbon of both spiro compounds
      had an S-configuration.

PMID- 14698906
TI  - Molecular analysis of a major soluble egg protein in the scleractinian coral
      Favites chinensis.
AB  - Soluble proteins were extracted from eggs of the scleractinian coral Favites
      chinensis, and analyzed using SDS-polyacrylamide gel electrophoresis. Two major
      proteins, named FcEP-1 and 2, were detected, and two partial amino acid sequences
      of FcEP-1 were determined. A cDNA encoding FcEP-1 was identified, using reverse
      transcription PCR with degenerate oligonucleotide primers designed based on the
      amino acid sequences, and rapid amplification of cDNA ends. Upon translation of
      the cDNA, FcEP-1 was predicted to consist of 648 amino acids, and the protein
      sequence exhibited similarity to vertebrate and invertebrate vitellogenins. FcEP
      1 transcripts were already present approximately 6 months before spawning, when
      the size of oocytes was approximately 1/60 of the mature egg, and could be
      detected throughout the vitellogenic period. These observations suggest that
      detection of FcEP-1 transcripts may be useful to monitor the vitellogenic
      activity in F. chinensis.

PMID- 14698907
TI  - Shrimp cathepsin L encoded by an intronless gene has predominant expression in
      hepatopancreas, and occurs in the nucleus of oocyte.
AB  - We have cloned the cDNA and genomic DNA of an active intronless cathepsin L from
      Metapenaeus ensis. The encoded enzyme has the shortest prosequence among
      cathepsin L subgroup. It was predominantly expressed in hepatopancreas with an
      expression level of at least 10 times higher than in any other tissues. It also
      has expression in stomach, intestine, eye, testis, ovary and muscle. Western
      blots visualized the mature enzyme in hepatopancreas and a procathepsin L in
      ovary, intestine and stomach. Metapenaeus cathepsin L (MeCatL) is localized in
      the large digestive vacuole of the digestive B cell of hepatopancreas. MeCatL has
      a role in food digestion. An interesting finding is that it exists in the nucleus
      of oocyte. MeCatL might have a specified physiological role in the nucleus of
      oocyte. MeCatL might also have a house-keeping function as is suggested for
      mammalian cathepsin L.

PMID- 14698908
TI  - Ascorbic acid decreases heat shock protein 70 and plasma corticosterone response
      in broilers (Gallus gallus domesticus) subjected to cyclic heat stress.
AB  - It is known that ascorbic acid (AA) supplementation can ameliorate the chicken's
      responses to heat stress. The influence of AA on heart heat shock protein 70
      (hsp70) and plasma corticosterone (CS) was evaluated in young male broiler
      chickens fed either no AA (N-AA) or 500 mg AA /kg (AA) and exposed to cyclic high
      temperatures (21 to 30 to 21 degrees C) over a 3.5 h period on three consecutive
      days. Dietary AA supplementation elevated plasma AA and maintained it at high
      levels after heating, but in N-AA birds, only heat elevated plasma AA. In N-AA
      fed chickens, plasma CS was elevated and was further increased by heat stress as
      compared with AA-fed birds. Heart hsp70 expression was greater in N-AA-fed
      chickens compared to AA-fed chickens, and heat stress further elevated hsp70 in
      both N-AA- and AA-fed birds. The hsp70 increase after heat was two-fold greater
      in N-AA- vs. AA-fed birds. Plasma CS and heart hsp70 were positively correlated,
      plasma AA and heart hsp70 were negatively correlated, and plasma CS and AA were
      negatively correlated. It was concluded that chickens experience a less severe
      stress response after exposure to high temperatures when they are provided
      dietary AA.

PMID- 14698909
TI  - Influence of exogenous thyroxine on plasma melatonin in juvenile Atlantic salmon
      (Salmo salar).
AB  - One of the most clearly defined endocrine changes during the parr-smolt
      transformation of anadromous salmonids is an increase in plasma levels of thyroid
      hormones. The role of pineal hormone melatonin in timing and synchronisation of
      smoltification is widely discussed. The effect of administration of exogenous
      thyroxine (T4) on plasma melatonin was investigated in juvenile Atlantic salmon
      (Salmo salar) at the early stages of parr-smolt transformation. Fish were kept in
      fresh water under simulated-natural photoperiod and exposed to exogenous T4. Fish
      were sampled at 12.00 and 24.00 h from treatment and control tanks, 2 and 14 days
      after treatment started. Plasma melatonin and L-thyroxine were measured using RIA
      and competitive enzyme immunoassay, respectively. After 2 days of T4 treatment,
      marked difference in plasma melatonin concentration measured at 12.00 and 24.00 h
      was still observed in both groups. However, 2-week exposure to T4 caused a
      reduction in night-time plasma melatonin level and thus, probably, inhibited
      melatonin related time-keeping system in juvenile salmon. Additional studies are
      needed to clarify the mechanism of the described phenomenon.

PMID- 14698910
TI  - Effects of water temperature and diets containing palm oil on fatty acid
      desaturation and oxidation in hepatocytes and intestinal enterocytes of rainbow
      trout (Oncorhynchus mykiss).
AB  - Food grade fisheries have reached their sustainable limits while aquaculture
      production has increased to meet consumer demands. However, for growth in
      aquaculture to continue and utilise sustainable, feeding ingredients,
      alternatives to fish oil (FO), the predominant lipid component of fish diets,
      must be developed. Therefore, there is currently considerable interest in the
      regulation of fatty acid metabolism in fish in order to determine strategies for
      the best use of plant oils in diets for commercially important cultured fish
      species. Plant oils are characteristically rich in C18 polyunsaturated fatty
      acids (PUFA) but devoid of C20 and C22 highly unsaturated fatty acids (HUFA)
      found in FO. The fatty acyl desaturase enzyme activities involved in the
      biosynthesis of HUFA from PUFA are known to be under nutritional regulation and
      can be increased in fish fed diets rich in plant oils. However, fatty acid
      desaturase activity is also known to be modulated by water temperature in fish.
      The present study aimed to investigate the interaction between water temperature
      and diet in the regulation of fatty acid metabolism in rainbow trout. Trout,
      acclimatized to 7, 11 or 15 degrees C, were fed for 4 weeks on diets in which the
      FO was replaced in a graded manner by palm oil. At the end of the trial, fatty
      acyl desaturation/elongation and beta-oxidation activities were determined in
      isolated hepatocytes and intestinal enterocytes using [1-14C]18:3n-3 as
      substrate, and samples of liver were collected for analysis of lipid and fatty
      acid composition. The most obvious effect of temperature was that fatty acid
      desaturation/elongation and beta-oxidation were reduced in both hepatocytes and
      intestinal enterocytes from fish maintained at the highest water temperature (15
      degrees C). There were differences between the two tissues with the highest
      desaturation/elongation and beta-oxidation activities tending to be in fish held
      at 11 degrees C in the case of hepatocytes, but 7 degrees C in enterocytes.
      Correlations between fatty acid metabolism and dietary palm oil were most clearly
      observed in desaturation/elongation activities in both hepatocytes and
      enterocytes at 11 degrees C. The highest beta-oxidation activities were generally
      observed in fish fed FO alone in both hepatocytes and enterocytes with palm oil
      having differential effects in the two cell types.

PMID- 14698911
TI  - Identification of hypothalamic genes implicated in the development of obesity in
      Psammomys obesus using differential display PCR.
AB  - The hypothalamus is a key central controller of energy homeostasis and is the
      source and/or site of action of many neuropeptides involved in this process. The
      aim of this study was to isolate hypothalamic genes differentially expressed
      between lean and obese Psammomys obesus, a polygenic animal model of obesity and
      type 2 diabetes. Differential display PCR was used to compare hypothalamic gene
      expression profiles of lean and healthy, obese and hyperinsulinemic, and obese,
      diabetic P. obesus in both the fed and fasted states. We conducted differential
      display with 180 separate primer combinations to amplify approximately 9,000
      expressed transcripts. Sixty differentially expressed bands were excised. Taqman
      PCR was performed on 36 of these transcripts to confirm differential gene
      expression in a larger sample population. Of these 36 transcripts, 9 showed
      homology to known genes, and 27 were considered to be novel sequences. Gene
      expression profiles for two of these genes are presented here. In conclusion,
      differential display PCR was successfully used to isolate several transcripts
      that may be involved in the central regulation of energy balance. We are
      currently conducting numerous studies to further investigate the role of these
      genes in the development of obesity in P. obesus.

PMID- 14698912
TI  - Polyamines of primitive apterygotan insects: springtails, silverfish and a
      bristletail.
AB  - Polyamines extracted from whole bodies of four springtails, Tomocerus ishibashii,
      Hypogastrura communis, Sinella cruviseta and Folsomia candida, a bristletail,
      Pedetontus nipponicus, and two silverfish, Lepisma saccharina and Thermobia
      domestica, were analyzed by high-performance liquid chromatography and gas
      chromatography. All seven apterous insect species contained putrescine,
      cadaverine and spermidine as the common major polyamines, detected at the level
      of micromol/g wet mass. T. ishibashii also contained spermine, S. cruviseta
      contained norspermidine and norspermine and H. communis, F. candida and P.
      nipponicus contained diaminopropane, norspermidine and norspermine, as minor
      polyamines above the detection limit (0.01 micromol/g wet mass). The occurrence
      of diaminopropane, norspermidine, norspermine, spermine and thermospermine was
      confirmed in L. saccharina and T. domestica. The novel polyamines norspermidine,
      norspermine and thermospermine, widespread in higher insects, were also
      distributed within the primitive apterygotan insects.

PMID- 14698913
TI  - Protection of neuronal cells against reactive oxygen species by carnosine and
      related compounds.
AB  - Carnosine and related compounds were compared in terms of their abilities to
      decrease the levels of reactive oxygen species (ROS) in suspensions of isolated
      neurons activated by N-methyl-D-aspartic acid (NMDA) using both stationary
      fluorescence measurements and flow cytometry. Carnosine was found to suppress the
      fluorescent signal induced by ROS production and decreased the proportion of
      highly fluorescent neurons, while histidine showed opposite effects. N-Acetylated
      derivatives of both carnosine and histidine demonstrated weak (statistically
      indistinguishable) suppressive effects on the ROS signal. N-Methylated
      derivatives of carnosine suppressed intracellular ROS generation to the same
      extent as carnosine. This rank of effectiveness is distinct from that previously
      obtained for the anti-radical ability of CRCs (anserine>carnosine>ophidine).
      These differences suggest that the similar ability of carnosine and its N
      methylated derivatives to protect neuronal cells against the excitotoxic effect
      of NMDA is not solely related to the antioxidant properties of these compounds.

PMID- 14698914
TI  - A chicken mRNA similar to heterogeneous nuclear ribonucleoprotein H1.
AB  - Heterogeneous nuclear ribonucleoproteins are predominantly nuclear RNA-binding
      proteins that function in a variety of cellular activities. The objective of
      these experiments was to clone a cDNA for a chicken protein similar to other
      previously reported heterogeneous ribonucleoproteins for other species. The 5'
      and 3' ends of the chicken mRNA were cloned using Rapid Amplification of cDNA
      Ends (RACE). Subsequently, the expression of the mRNA sequence was confirmed via
      Northern analysis. The deduced amino acid sequence was approximately 86%
      identical to corresponding regions of human, mouse, or zebrafish proteins similar
      to heterogeneous nuclear ribonucleoprotein H1. The expression data confirmed the
      size of the predicted mRNA sequence. The newly identified sequence may be
      employed in future studies aimed at understanding the role of heterogeneous
      nuclear ribonucleoproteins in avian species.

PMID- 14698915
TI  - Purification and characterization of glutathione S-transferases from two syrphid
      flies (Syrphus ribesii and Myathropa florae).
AB  - Glutathione S-transferases (GST) play an important role in the detoxification of
      many substances including organic pollutants and plant secondary metabolites. We
      compared the GST of two syrphid species, the aphidophagous Syrphus ribesii and
      the saprophagous Myathropa florea to assess the relation between feeding type and
      GST patterns. Differences between the GST of the hoverfly species were observed
      after purification by affinity chromatography, SDS-PAGE and kinetic studies.
      While the specific activities of the purified enzymes were different, the
      purification yields were similar. The variation in specific activities was
      related to the presence of different isoenzymes in both syrphid species by SDS
      PAGE. While two bands of 24 and 32 kDa were observed for M. florea, one more band
      of 26 kDa was present in S. ribesii. When a range of substrate and glutathione
      concentrations was tested, differences in Km and Vmax between the glutathione S
      transferases from both hoverfly species were also observed. These results are
      discussed in terms of adaptations to the feeding habit and the habitat of the two
      syrphid species.

PMID- 14698916
TI  - Sex-specific metabolic changes in the annual reproductive cycle of a freshwater
      catfish.
AB  - Sex-specific enzymatic and other biochemical changes were studied in the annual
      reproductive cycle of the freshwater catfish, Clarias batrachus. Citrate synthase
      (CS) activity of brain, liver and skeletal muscle was maximum in spawning and
      minimum in postspawning showing a sharp decline in aerobic capacity after
      spawning. Similar CS activity in remaining phases of the annual reproductive
      cycle reflects similar energy need during regressed, preparatory and prespawning
      phases. Glucose 6-phosphate dehydrogenase (G6-PDH) activity declined in spawning
      and postspawning indicating a possible decrease in lipid and nucleic acid
      syntheses. The subsequent increase in G6-PDH activity with onset of resting and
      maintenance of the increased level throughout preparatory and prespawning phases
      shows restoration of biosynthetic activity. Higher activity of G6-PDH in female
      than male may be to satisfy a greater biosynthetic need of female reproduction
      and breeding. The decreased RNA content of tissues showed reduction in protein
      synthesis capacity during spawning and subsequent increase through postspawning
      until resting phase. The RNA content of brain and liver was higher in female than
      male during preparatory and prespawning, which may be associated with higher
      protein synthesis requirement of female for preparation of reproductive
      activities. The requirement based sex related changes in metabolism of catfish
      may be enzyme, tissue or reproductive phase-specific.

PMID- 14698917
TI  - Molecular characterization of cathepsin L from hepatopancreas of the carp
      Cyprinus carpio.
AB  - Purified cathepsin L from carp, Cyprinus carpio, consists of a 28 kDa single
      chain form that is different from the 24 and 5 kDa mammalian two-chain form. We
      cloned cathepsin L from carp hepatopancreas. The sequence consisted of a 1490 bp
      cDNA and a 1014 bp open reading frame, encoding a deduced protein of 337 amino
      acids that is likely processed to an active enzyme (single-chain form) with 222
      amino acids. Its similarity to other types of vertebrate cathepsin L is less than
      69%. Mammalian cathepsin L is further processed to a two-chain form, but possibly
      this is not the case with carp cathepsin L: the P1 site where cleavage occurred
      in the two-chain form of mammalian cathepsin L contains a serine, while carp
      cathepsin L processes a valine. Therefore, carp cathepsin L may have a different
      mechanism of action from mammalian cathepsin L.

PMID- 14698918
TI  - The interaction of FBPase with aldolase: a kinetic and fluorescence investigation
      on chicken muscle enzymes.
AB  - Fructose-1,6-bisphosphatase (FBPase; EC 3.1.3.11) is strongly inhibited by AMP in
      vitro and, therefore, at physiological concentrations of substrate and AMP,
      FBPase should be completely inhibited. Desensitization of rabbit muscle FBPase
      against AMP inhibition was previously observed in the presence of rabbit muscle
      aldolase. In this study, we analysed the kinetics of an FBPase catalyzed reaction
      and interaction between chicken muscle FBPase and chicken muscle aldolase. The
      initial rate of FBPase reaction vs. substrate concentration shows a maximum
      activity at a concentration of 20 microM Fru-1,6P2 and then decreases. Assuming
      rapid equilibrium kinetics, the enzyme-catalyzed reaction was described by the
      substrate inhibition model, with Ks approximately 5 microM and Ksi approximately
      39 microM and factor beta approximately 0.2, describing change in the rate
      constant (k) of product formation from the ES and ESSi complexes. Based on
      ultracentrifugation studies, aldolase and FBPase form a hetero-complex with
      approximately 1:1 stoichiometry with a dissociation constant (Kd) of 3.8 microM.
      The FBPase-aldolase interaction was confirmed via fluorescence investigation. The
      aldolase-FBPase interaction results in aldolase fluorescence quenching and its
      maximum emission spectrum shifting from 344 to 356 nm. The Kd of the FBPase
      aldolase complex, determined on the basis of fluorescence changes, is 0.4 microM
      at 25 degrees C with almost 1:1 stoichiometry. This interaction increases the
      I(0.5) for the AMP inhibition of FBPase threefold, and slightly affects FBPase
      affinity to magnesium ions, increasing the Ka and Hill coefficient (n). No effect
      of aldolase on the FBPase pH optimum was observed. Thus, the decrease in FBPase
      sensitivity to AMP inhibition enables FBPase to function in vivo thanks to
      aldolase.

PMID- 14698919
TI  - Evolution and expression of the amphioxus AmphiHMGB gene encoding an HMG-box
      protein.
AB  - Amphioxus HMGB gene, AmphiHMGB, encoding a high mobility group (HMG) protein was
      identified from the gut cDNA library of Branchiostoma belcheri tsingtauense.
      Primary structural examination indicates that it is a member of HMGB family.
      Molecular phylogenetic analysis suggests that AmphiHMGB represents the archetype
      of chordate HMGB genes including HMGB1, HMGB2 and HMGB3 although it may have lost
      its C-terminal domain during evolution. Northern blotting revealed that AmphiHMGB
      expression was restricted mainly to guts in the adult, and AmphiHMGB transcripts
      were in greater abundance in gastrula and neurula though they were markedly low
      in 1-day larva.

PMID- 14698920
TI  - Purification and characterization of myofibril-bound serine protease from lizard
      fish (Saurida undosquamis) muscle.
AB  - Myofibril-bound serine protease (MBSP) from lizard fish (SAURIDA UNDOSQUAMIS:
      Synodontidae) skeletal muscle was purified to homogeneity with higher
      purification (1260-fold) and higher recovery (7%) than our previous report in
      lizard fish (Saurida wanieso). The new purification method combines a heat
      treatment for dissociation from washed myofibrils, acid-treatment at pH 5.0
      before and after lyophilization, and alcohol-treatment, followed by two column
      chromatographies. The molecular mass of the enzyme was estimated to be 50 kDa
      under non-reducing conditions and 28 kDa under reducing conditions by SDS-PAGE.
      The N-terminal amino acid sequence of the MBSP was determined to be 22 residues
      (IVGGYEXEAYSKPYQVSINLGY) and the sequence showed high homology to carp and other
      fish trypsins (64-77%), but did not show high homology to carp MBSP (41%). The
      enzyme activity was inhibited by serine protease inhibitors such as Pefabloc SC,
      leupeptin, TLCK and native protein inhibitors (soybean trypsin inhibitor,
      alpha(1)-antitrypsin and aprotinin). The purified enzyme specifically hydrolyzed
      at the carboxyl side of the arginine residue of synthetic 4-methyl-coumaryl-7
      amide substrate. When purified MBSP was stored at -35 degrees C in the presence
      of 50% ethylene glycol (V/V), the enzyme activity was entirely preserved over 6
      months and stable against freezing and thawing. Activities for both casein and
      the synthetic substrate were most active at pH 9.0, and the enzyme was most
      active approximately 55 degrees C with casein and between 35 and 45 degrees C for
      synthetic substrate. When myofibrils were incubated with purified MBSP, myosin
      heavy chain was mostly degraded approximately 55 degrees C, but the degradation
      of actin was very slow.

PMID- 14698921
TI  - Identification of histone H1.z components in a Muscovy duck (Cairina moschata L.)
      population.
AB  - The general patterns of histone H1 proteins from erythrocyte nuclei of Muscovy
      duck individuals were similar to those of Pekin type ducks both in acetic acid
      urea and 2D polyacrylamide gels. We show here that Muscovy duck histone H1.z in
      the tested population was represented by three different electromorphs, each
      presumably encoded by a distinct allelic gene. Accordingly, we have identified
      six phenotypes consisting of the homodimeric and heterodimeric combinations of
      the three isoforms. The frequency of the presumptive alleles ranged from 0.506
      for the main allele z1 to 0.379 for allele z2 and only 0.113 for the rarest
      allele z3. In addition to a standard set of somatic H1 variants, an unusual
      protein X, absent in other avian species, was also revealed.

PMID- 14698922
TI  - "Getting the lead out" in Hartford, Connecticut: a multifaceted lead-poisoning
      awareness campaign.
AB  - As part of a citywide effort to increase lead poisoning awareness within the city
      of Hartford, Connecticut, the Hartford Health Department implemented a
      multifaceted public health campaign involving several novel elements and
      partnerships, including the use of municipal sanitation trucks to disseminate
      lead-poisoning prevention messages throughout the city. To evaluate campaign
      reach and effectiveness, Health Department personnel collected measures of lead
      poisoning knowledge, recall of campaign components, and reports of steps taken to
      prevent lead poisoning from 180 largely ethnic minority parents of preschool-age
      children. Key results were as follows: a) Recall of campaign components ranged
      from 21.5 to 62.6%, with newspaper advertisements and signs on buses and
      billboards recalled most often and a video broadcast on public-access television
      recalled least often. b) More than 45% of respondents reported that they took
      steps to prevent lead poisoning because of at least one of the campaign
      components, with the newspaper advertisements being the most effective component
      in terms of prompting lead-poisoning prevention behavior. c) Respondents'
      awareness was particularly low in terms of how medical personnel and procedures
      can and cannot detect and prevent lead poisoning in children. This campaign
      prompted caregivers to take steps to prevent lead poisoning and may help public
      health professionals in other communities to develop novel ideas through which to
      embark on similar initiatives.

PMID- 14698923
TI  - A retrospective assessment of mortality from the London smog episode of 1952: the
      role of influenza and pollution.
AB  - The London smog of 1952 is one of history's most important air pollution episodes
      in terms of its impact on science, public perception of air pollution, and
      government regulation. The association between health and air pollution during
      the episode was evident as a strong rise in air pollution levels was immediately
      followed by sharp increases in mortality and morbidity. However, mortality in the
      months after the smog was also elevated above normal levels. An initial
      government report proposed the hypothesis that influenza was responsible for high
      mortality during these months. Estimates of the number of influenza deaths were
      generated using multiple methods, indicating that only a fraction of the deaths
      in the months after the smog could be attributable to influenza. Sensitivity
      analysis reveals that only an extremely severe influenza epidemic could account
      for the majority of the excess deaths for this time period. Such an epidemic
      would be on the order of twice the case-fatality rate and quadruple the incidence
      observed in a general medical practice during the winter of 1953. These results
      underscore the need for diligence regarding extremely high air pollution that
      still exists in many parts of the world.

PMID- 14698924
TI  - Brominated flame retardants: cause for concern?
AB  - Brominated flame retardants (BFRs) have routinely been added to consumer products
      for several decades in a successful effort to reduce fire-related injury and
      property damage. Recently, concern for this emerging class of chemicals has risen
      because of the occurrence of several classes of BFRs in the environment and in
      human biota. The widespread production and use of BFRs; strong evidence of
      increasing contamination of the environment, wildlife, and people; and limited
      knowledge of potential effects heighten the importance of identifying emerging
      issues associated with the use of BFRs. In this article, we briefly review
      scientific issues associated with the use of tetrabromobisphenol A,
      hexabromocyclododecane, and three commercial mixtures of polybrominated diphenyl
      ethers and discuss data gaps. Overall, the toxicology database is very limited;
      the current literature is incomplete and often conflicting. Available data,
      however, raise concern over the use of certain classes of brominated flame
      retardants.

PMID- 14698925
TI  - Mean total arsenic concentrations in chicken 1989-2000 and estimated exposures
      for consumers of chicken.
AB  - The purpose of this study was to estimate mean concentrations of total arsenic in
      chicken liver tissue and then estimate total and inorganic arsenic ingested by
      humans through chicken consumption. We used national monitoring data from the
      Food Safety and Inspection Service National Residue Program to estimate mean
      arsenic concentrations for 1994-2000. Incorporating assumptions about the
      concentrations of arsenic in liver and muscle tissues as well as the proportions
      of inorganic and organic arsenic, we then applied the estimates to national
      chicken consumption data to calculate inorganic, organic, and total arsenic
      ingested by eating chicken. The mean concentration of total arsenic in young
      chickens was 0.39 ppm, 3- to 4-fold higher than in other poultry and meat. At
      mean levels of chicken consumption (60 g/person/day), people may ingest 1.38-5.24
      microg/day of inorganic arsenic from chicken alone. At the 99th percentile of
      chicken consumption (350 g chicken/day), people may ingest 21.13-30.59 microg
      inorganic arsenic/day and 32.50-47.07 microg total arsenic/day from chicken.
      These concentrations are higher than previously recognized in chicken, which may
      necessitate adjustments to estimates of arsenic ingested through diet and may
      need to be considered when estimating overall exposure to arsenic.

PMID- 14698927
TI  - Closing the research loop: a risk-based approach for communicating results of air
      pollution exposure studies.
AB  - Communities have long been concerned about the environmental health and
      environmental quality of their neighborhoods. Community-based exposure
      assessments have the potential to be an effective way to address these concerns.
      The success of such studies depends critically on the effective translation and
      communication of study results back to the study participants and the community.
      In this article we describe the communication approach applied as part of the
      South Baltimore Community Exposure Study. Specifically, in conjunction with
      collecting measurements, we asked the community to define questions they wanted
      answered and the way in which they wanted to receive study results. To meet their
      needs, we applied the risk assessment framework. The approach we developed helped
      residents interpret exposure assessment measurements and gave them the raw
      materials to effect change in their community. The risk-based approach to
      presenting participant and community results provides the means to move beyond
      traditional reporting of concentration values in three important ways. First,
      risk takes into consideration toxicity, thereby enabling a dialogue about
      community health concerns. Second, risk provides a common denominator so that
      exposure and risk can be compared and priorities identified. Third, exposure and
      risk can be summed, thereby meeting the community's need for information
      regarding cumulative exposure. This approach may be a useful model for other
      researchers conducting exposure assessments in response to community concerns.

PMID- 14698926
TI  - Relationship of serum TCDD concentrations and age at exposure of female residents
      of Seveso, Italy.
AB  - In 1976, a chemical plant explosion near Seveso, Italy, resulted in the highest
      known exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in residential
      populations. In 1996, we initiated the Seveso Women's Health Study (SWHS), a
      historical cohort study of females who were 40 years old at the time of explosion
      and residents of the most heavily contaminated areas, zones A and B. Serum
      samples collected near the time of the explosion were analyzed for TCDD. We also
      analyzed pooled serum samples collected in 1976 from females who resided in zone
      non-ABR, the "unexposed" zone, to assess concurrent background exposures to other
      dioxins, furans, and coplanar polychlorinated biphenyls (PCBs). The median lipid
      adjusted TCDD level for residents of zones A and B combined was 56 ppt (range =
      2.5-56,000 ppt). Zone A residents had 5-fold higher TCDD levels (n = 67, median =
      272 ppt) than did zone B residents (n = 814, median = 47 ppt). The youngest
      children had the highest TCDD levels, which decreased with age at explosion until
      approximately 13 years of age and were constant thereafter. Therefore, children
      living in zones A and B received a disproportionately higher exposure to TCDD as
      a result of the explosion. Zone of residence and age were the strongest
      predictors of TCDD level. Chloracne, nearby animal mortality, location (outdoors
      vs. indoors) at the time of explosion, and consumption of homegrown food were
      also related to serum TCDD levels. The serum pools from zone non-ABR residents
      had an average TCDD concentration of 20.2 ppt, and average total toxic equivalent
      (TEQ) concentration of 100.4 ppt. Therefore, background exposure to dioxins,
      furans, and PCBs unrelated to the explosion may have been substantial. As a
      consequence, previous SWHS studies that considered only TCDD exposure may have
      underestimated health effects due to total TEQ concentrations.

PMID- 14698928
TI  - Lead, arsenic, and polycyclic aromatic hydrocarbons in soil and house dust in the
      communities surrounding the Sydney, Nova Scotia, tar ponds.
AB  - This study evaluated lead, arsenic, and polycyclic aromatic hydrocarbon (PAH)
      contamination in the residential communities adjacent to the Sydney, Nova Scotia,
      tar ponds, the area considered Canada's worst contaminated site. The tar pond
      remediation policy has been limited to the site and some residential properties.
      We compared background concentrations in 91 soil samples taken 5-20 km from the
      coke oven site with those in soil samples from the three communities surrounding
      the tar ponds: Whitney Pier, Ashby, and North End. These surrounding communities
      were statistically different from background regarding arsenic, lead, and PAHs.
      Twenty percent of the background soil samples and 95% of the tar pond soil
      samples were above the Canadian health-risk-based soil guidelines for arsenic (12
      ppm), and 5% of the background samples and 80% of the tar pond soil samples were
      above the Canadian guidelines for lead (140 ppm). Regarding dust lead and arsenic
      loading, the results provide no evidence that Whitney Pier is significantly
      different than Ashby and North End. Children in these communities are predicted
      to have a 1-15% chance of blood lead > 10 microg/dL. The results suggest that
      lead and arsenic found in the homes originate outside. The lead content of paint
      in the homes was not evaluated, but consideration of painted wood at the doorway
      did not confound the results of the study. The results indicate that the
      residential environment has been adversely affected by PAHs, lead, and arsenic
      and should be considered for remediation.

PMID- 14698929
TI  - Correlation between blood ethylenethiourea and thyroid gland disorders among
      banana plantation workers in the Philippines.
AB  - Ethylenebisdithiocarbamates (EBDCs) are metabolized into ethylenethiourea (ETU),
      a possible human carcinogen and an antithyroid compound. In this study our goal
      was to correlate ETU levels with the incidence of thyroid gland disorders among
      banana plantation workers exposed to EBDC. We randomly selected 57 directly
      exposed workers and 31 indirectly exposed workers from four banana plantations
      and 43 workers from an organic farm; all subjects underwent complete medical
      examinations and laboratory tests. Results showed a higher mean thyroid
      stimulating hormone measurement among exposed workers compared with the control
      group, although the levels were well within normal range. Nine of the exposed
      farmers had abnormal thyroid ultrasound findings, consisting mostly of solitary
      nodules, compared with three among the control group. Analysis of variance showed
      significantly different blood ETU levels among the directly exposed, indirectly
      exposed, and control groups (p < 0.001), but ETU levels in urine were not
      significantly different (p = 0.10). Environmental ETU levels were below the U.S.
      Environmental Protection Agency remediation levels. Among farmers with solitary
      thyroid nodules, we found a very good direct correlation between the size of the
      nodule and blood ETU level. In this study we showed that blood ETU is a more
      reliable biomarker for EBDC exposure than urinary ETU; therefore, the
      determination of blood ETU should be part of medical surveillance efforts among
      workers exposed to EBDC to detect occurrences of thyroid gland disorders.

PMID- 14698930
TI  - Long-term neurobehavioral health effects of methyl parathion exposure in children
      in Mississippi and Ohio.
AB  - Methyl parathion (MP), an organophosphate pesticide licensed only for
      agricultural uses, was sprayed illegally for pest control in Mississippi and Ohio
      residences. To evaluate the association between MP exposure and neurobehavioral
      development, we assessed children 6 years or younger at the time of the spraying
      and local comparison groups of unexposed children using the Pediatric
      Environmental Neurobehavioral Test Battery (PENTB). The PENTB is composed of
      informant-based procedures (parent interview and questionnaires) and performance
      based procedures (neurobehavioral tests for children 4 years or older) that
      evaluate cognitive, motor, sensory, and affect domains essential to
      neurobehavioral assessment. Children were classified as exposed or unexposed on
      the basis of urinary para-nitrophenol levels and environmental wipe samples for
      MP. Exposed children had more difficulties with tasks involving short-term memory
      and attention. Additionally, parents of exposed children reported that their
      children had more behavioral and motor skill problems than did parents of
      unexposed children. However, these effects were not consistently seen at both
      sites. There were no differences between exposed and unexposed children in tests
      for general intelligence, the integration of visual and motor skills, and
      multistep processing. Our findings suggest that MP might be associated with
      subtle changes to short-term memory and attention and contribute to problems with
      motor skills and some behaviors, but the results of the study are not conclusive.

PMID- 14698931
TI  - Identification of sources of lead in children in a primary zinc-lead smelter
      environment.
AB  - We compared high-precision lead isotopic ratios in deciduous teeth and
      environmental samples to evaluate sources of lead in 10 children from six houses
      in a primary zinc-lead smelter community at North Lake Macquarie, New South
      Wales, Australia. Teeth were sectioned to allow identification of lead exposure
      in utero and in early childhood. Blood lead levels in the children ranged from 10
      to 42 micro g/dL and remained elevated for a number of years. For most children,
      only a small contribution to tooth lead can be attributed to gasoline and paint
      sources. In one child with a blood lead concentration of 19.7 microg/dL, paint
      could account for about 45% of lead in her blood. Comparison of isotopic ratios
      of tooth lead levels with those from vacuum cleaner dust, dust-fall accumulation,
      surface wipes, ceiling (attic) dust, and an estimation of the smelter emissions
      indicates that from approximately 55 to 100% of lead could be derived from the
      smelter. For a blood sample from another child, > 90% of lead could be derived
      from the smelter. We found varying amounts of in utero-derived lead in the teeth.
      Despite the contaminated environment and high blood lead concentrations in the
      children, the levels of lead in the teeth are surprisingly low compared with
      those measured in children from other lead mining and smelting communities.

PMID- 14698932
TI  - Proximity of California public schools to busy roads.
AB  - Residential proximity to busy roads has been associated with adverse health
      outcomes, and school location may also be an important determinant of children's
      exposure to traffic-related pollutants. The goal of this study was to examine the
      characteristics of public schools (grades K-12) in California (n = 7,460) by
      proximity to major roads. We determined maximum daily traffic counts for all
      roads within 150 m of the school using a statewide road network and a geographic
      information system. Statewide, 173 schools (2.3%) with a total enrollment of
      150,323 students were located within 150 m of high-traffic roads (greater than or
      equal to 50,000 vehicles/day); 536 schools (7.2%) were within 150 m of medium
      traffic roads (25,000-49,999 vehicles/day). Traffic exposure was related to
      race/ethnicity. For example, the overall percentage of nonwhite students was 78%
      at the schools located near high-traffic roads versus 60% at the schools with
      very low exposure (no streets with counted traffic data within 150 m). As the
      traffic exposure of schools increased, the percentage of both non-Hispanic black
      and Hispanic students attending the schools increased substantially. Traffic
      exposure was also related to school-based and census-tract-based socioeconomic
      indicators, including English language learners. The median percentage of
      children enrolled in free or reduced-price meal programs increased from 40.7% in
      the group with very low exposure to 60.5% in the highest exposure group. In
      summary, a substantial number of children in California attend schools close to
      major roads with very high traffic counts, and a disproportionate number of those
      students are economically disadvantaged and nonwhite.

PMID- 14698933
TI  - Our once-in-a-lifetime opportunity.
AB  - Longitudinal studies of the determinants of children's health are complex,
      costly, infrequent, and incredibly valuable. It has become clear in recent years
      that the periconceptional environment plays a surprisingly large role in the
      health of the resulting child. This short introduction to this mini-monograph
      briefly recaps the articles included herein and reminds us that adequate
      forethought and planning will result in a study that could shed new light on the
      earliest determinants of children's health and thereby fill critical data gaps.

PMID- 14698935
TI  - Prospective pregnancy study designs for assessing reproductive and developmental
      toxicants.
AB  - The determinants of successful human reproduction and development may act as
      early as periconceptionally, underscoring the need to capture exposures during
      these critical windows when assessing potential toxicants. To identify such
      toxicants, couples must be studied longitudinally prior to conception without
      regard to a couple's ability to ascertain a clinically recognized pregnancy. We
      examined the utility and feasibility of prospective pregnancy study designs by
      conducting a systematic review of the literature to summarize relevant
      information regarding the planning, implementation, and success of previously
      published prospective pregnancy studies. Information concerning design elements
      and participation was abstracted from 15 eligible studies (from a total of 20
      identified studies) using a standardized form. The primary author of each study
      was contacted to review our summary of their work and obtain missing information.
      Our findings confirm the ability to recruit women/couples from diverse
      populations using a variety of recruitment strategies. Among the studies we
      reviewed, 4-97% of eligible individuals were successfully contacted, with
      enrollment rates ranging from 42 to 100%. Length of follow-up varied from 3 to 12
      months. A high percentage of women provided urine (57-98%) and blood (86-91%)
      specimens and most male partners (94-100%) provided semen samples. These data
      support the feasibility of this design.

PMID- 14698934
TI  - Off to a good start: the influence of pre- and periconceptional exposures,
      parental fertility, and nutrition on children's health.
AB  - The scientific community is developing a compelling body of evidence that shows
      the importance of the in utero environment (including chemical and hormonal
      levels) to the ultimate health of the child and even of the aging adult. This
      article summarizes the evidence that shows this impact begins with conception.
      Only a full life-cycle evaluation will help us understand these impacts, and only
      such an understanding will produce logically prioritized mitigation strategies to
      address the greatest threats first. Clearly, the time for analysis begins when
      the next generation is but a twinkle in the eye.

PMID- 14698936
TI  - Methodologic and statistical approaches to studying human fertility and
      environmental exposure.
AB  - Although there has been growing concern about the effects of environmental
      exposures on human fertility, standard epidemiologic study designs may not
      collect sufficient data to identify subtle effects while properly adjusting for
      confounding. In particular, results from conventional time to pregnancy studies
      can be driven by the many sources of bias inherent in these studies. By
      prospectively collecting detailed records of menstrual bleeding, occurrences of
      intercourse, and a marker of ovulation day in each menstrual cycle, precise
      information on exposure effects can be obtained, adjusting for many of the
      primary sources of bias. This article provides an overview of the different types
      of study designs, focusing on the data required, the practical advantages and
      disadvantages of each design, and the statistical methods required to take full
      advantage of the available data. We conclude that detailed prospective studies
      allowing inferences on day-specific probabilities of conception should be
      considered as the gold standard for studying the effects of environmental
      exposures on fertility.

PMID- 14698939
TI  - Embedded in nature: human health and biodiversity.

PMID- 14698937
TI  - The value of home-based collection of biospecimens in reproductive epidemiology.
AB  - Detection, quantification, and prognosis of environmental exposures in humans has
      been vastly enhanced by the ability of epidemiologists to collect biospecimens
      for toxicologic or other laboratory evaluation. Ease of collection and level of
      invasiveness are commonly cited reasons why study participants fail to provide
      biospecimens for research purposes. The use of methodologies for the collection
      of biospecimens in the home offers promise for improving the validity of health
      effects linked to environmental exposures while maximizing the number and type of
      specimens capable of being collected in a timely and cost-effective manner. In
      this review we examine biospecimens (urine and blood) that have been successfully
      collected from the home environment. Related issues such as storage and
      transportation will also be examined as well as promising new approaches for
      collecting less frequently studied biospecimens (including hair follicles, breast
      milk, semen, and others). Such biospecimens are useful in the monitoring of
      reproductive development and function.

PMID- 14698938
TI  - Biomarkers for assessing reproductive development and health: Part 1--Pubertal
      development.
AB  - The proposed National Children's Study has helped raise awareness of the issues
      related to children's health and the importance of monitoring the growth and
      development of children from preconception through adulthood. Many genetic
      predispositions can adversely impact the normal development process, and various
      environmental exposures have been linked to adverse reproductive health in rodent
      models and a small number of accidental human exposures. To monitor reproductive
      health and identify adverse effects at the earliest possible juncture,
      investigators must develop a network of biomarkers covering all stages and
      aspects of reproductive development and function. Biomarkers are biological
      indicators that can be measured repeatedly and are informative on one or more
      aspects of biological development or function. They can range from the anatomical
      level down to the molecular level and may provide information on the nature of an
      exposure, the effect of an exposure, or the susceptibility of individuals or
      populations to the toxic effects of an exposure. In theory, biomarkers can be
      used to monitor a wide variety of conditions and responses ranging from abnormal
      development to early indicators of late-onset disease. The main stumbling block
      with this theory has been finding appropriate biomarkers for particular
      conditions and exposures. Such biomarkers must be easily accessible, robust, and
      sensitive. Ideally, they will be expressed across a large section of the
      population, and can be monitored quickly, easily, conveniently, and with minimal
      cost. In this review, we discuss some of the current and emerging biomarkers of
      human pubertal development.

PMID- 14698941
TI  - The Center for Regulatory Effectiveness invokes the Data Quality Act to reject
      published studies on atrazine toxicity.

PMID- 14698943
TI  - Risk of arsenic contamination in groundwater affecting the Ganga Alluvial Plain,
      India.

PMID- 14698947
TI  - Paying attention to neglected diseases.

PMID- 14698945
TI  - Re: "Increased concentrations of polychlorinated biphenyls, hexachlorobenzenes,
      and chlordanes in mothers of men with testicular cancer".

PMID- 14698948
TI  - The link between disparity and disease.

PMID- 14698949
TI  - Infectious disease: the human costs of our environmental errors.

PMID- 14698950
TI  - Diet and dioxins: the need to cut back.

PMID- 14698951
TI  - Constructed wetlands: borrowing a concept from nature.

PMID- 14698953
TI  - Risk management frameworks for human health and environmental risks.
AB  - A comprehensive analytical review of the risk assessment, risk management, and
      risk communication approaches currently being undertaken by key national,
      provincial/state, territorial, and international agencies was conducted. The
      information acquired for review was used to identify the differences,
      commonalities, strengths, and weaknesses among the various approaches, and to
      identify elements that should be included in an effective, current, and
      comprehensive approach applicable to environmental, human health and occupational
      health risks. More than 80 agencies, organizations, and advisory councils,
      encompassing more than 100 risk documents, were examined during the period from
      February 2000 until November 2002. An overview was made of the most important
      general frameworks for risk assessment, risk management, and risk communication
      for human health and ecological risk, and for occupational health risk. In
      addition, frameworks for specific applications were reviewed and summarized,
      including those for (1)contaminated sites; (2) northern contaminants; (3)
      priority substances; (4) standards development; (5) food safety; (6) medical
      devices; (7) prescription drug use; (8) emergency response; (9) transportation;
      (10) risk communication. Twelve frameworks were selected for more extensive
      review on the basis of representation of the areas of human health, ecological,
      and occupational health risk; relevance to Canadian risk management needs;
      representation of comprehensive and well-defined approaches; generalizability
      with their risk areas; representation of "state of the art" in Canada, the United
      States, and/or internationally; and extent of usage of potential usage within
      Canada. These 12 frameworks were: 1. Framework for Environmental Health Risk
      Management (US Presidential/Congressional Commission on Risk Assessment and Risk
      Management, 1997). 2. Health Risk Determination: The Challenge of Health
      Protection (Health and Welfare Canada, 1990). 3. Health Canada Decision-Making
      Framework for Identifying, Assessing and Managing Health Risks (Health Canada,
      2000). 4. Canadian Environmental Protection Act: Human Health Risk Assessment of
      Priority Substances(Health Canada, 1994). 5. CSA-Q8550 Risk Management:
      Guidelines for Decision-Makers (Canada Standards Association, 1997). 6. Risk
      Assessment in the Federal Government: Managing the Process (US National Research
      Council, 1983). 7. Understanding Risk: Informing Decisions in a Democratic
      Society (US National Research Council, 1996). 8. Environmental Health Risk
      Assessment (enHealth Council of Australia, 2002). 9. A Framework for Ecological
      Risk Assessment (CCME, 1996). 10. Ecological Risk Assessments of Priority
      Substances Under the Canadian Environmental Protection Act (Environment Canada,
      1996).11. Guidelines for Ecological Risk Assessment (US EPA, 1998b). 12. Proposed
      Model for Occupational Health Risk Assessment and Management (Rampal & Sadhra,
      1999). Based on the extensive review of these frameworks, seven key elements that
      should be included in a comprehensive framework for human health, ecological, and
      occupational risk assessment and management were identified: 1. Problem
      formulation stage. 2. Stakeholder involvement. 3. Communication. 4. Quantitative
      risk assessment components. 5. Iteration and evaluation. 6. Informed decision
      making. 7. Flexibility. On the basis of this overarching approach to risk
      management, the following "checklist" to ensure a good risk management decision
      is proposed: - Make sure you're solving the right problem. - Consider the problem
      and the risk within the full context of the situation, using a broad perspective.
      - Acknowledge, incorporate, and balance the multiple dimensions of risk. - Ensure
      the highest degree of reliability for all components of the risk management
      process. - Involve interested and effected parties from the outset of the
      process. - Commit to honest and open communication between all parties. - Employ
      continuous evaluation throughout the process (formative, process, and outcome
      evaluation), and be prepared to change the decision if new information becomes
      available. Comprehensive and sound principles are critical to providing structure
      and integrity to risk management frameworks. Guiding principles are intended to
      provide an ethical grounding for considering the many factors involved in risk
      management decision making. Ten principles are proposed to guide risk management
      decision making. The first four principles were adapted and modified from Hattis
      (1996) along with the addition of two more principles by Hrudey (2000). These
      have been supplemented by another four principles to make the 10 presented. The
      principles are based in fundamental ethical principles and values. These
      principles are intended to be aspirational rather than prescriptive--their
      application requires flexibility and practical judgement. Risk management is
      inherently a process in search of balance among competing interests and concerns.
      Each risk management decision will be "balancing act" of competing priorities,
      and trade-offs may sometimes have to be made between seemingly conflicting
      principles. The 10 decision-making principles, with the corresponding ethical
      principle in italics are: 1. Do more good than harm (beneficence,
      nonmalificence).- The ultimate goal of good risk management is to prevent or
      minimize risk, or to "do good" as much as possible. 2. Fair process of decision
      making (fairness, natural justice). - Risk management must be just, equitable,
      impartial, unbiased, dispassionate, and objective as far as possible given the
      circumstances of each situation. 3. Ensure an equitable distribution of risk
      (equity). - An equitable process of risk management would ensure fair outcomes
      and equal treatment of all concerned through an equal distribution of benefits
      and burdens (includes the concept of distributive justice, i.e., equal
      opportunities for all individuals). 4. Seek optimal use of limited risk
      management resources (utility). - Optimal risk management demands using limited
      resources where they will achieve the most risk reduction of overall benefit. 5.
      Promise no more risk management that can be delivered (honesty).- Unrealistic
      expectations of risk management can be avoided with honest and candid public
      accounting of what we know and don't know, and what we can and can't do using
      risk assessment and risk management. 6. Impose no more risk that you would
      tolerate yourself (the Golden Rule). - The Golden Rule is important in risk
      management because it forces decision makers to abandon complete detachment from
      their decisions so they may understand the perspectives of those affected. 7. Be
      cautious in the face of uncertainty ("better safe than sorry"). - Risk management
      must adopt a cautious approach when faced with a potentially serous risk, even if
      the evidence is uncertain. 8. Foster informed risk decision making for all
      stakeholders (autonomy). - Fostering autonomous decision making involves both
      providing people with the opportunity to participate, and full and honest
      disclosure of all the information required for informed decisions. 9. Risk
      management processes must be flexible and evolutionary to be open to new
      knowledge and understanding (evolution, evaluation, iterative process). - The
      incorporation of new evidence requires that risk management be a flexible,
      evolutionary, and iterative process, and that evaluation is employed at the
      beginning and througthout the process. 10. the complete elimination fo risk is
      not possible (life is not risk free).- Risk is pervasive in our society, and
      cannot be totally eliminated despite an oft-expressed public desire for "zero
      risk". However, the level of risk that may ve tolerable by any individual is
      dependent on values of beliefs, as well as scientific information. Each agency
      must continue to employ a process that meets the needs of their specific
      application of risk management. A single approach cannot satisfy the diverse
      areas to which risk decisions are being applied. However, with increasing
      experience in the application of the approaches, we are evolving to a common
      understanding of the essential elements and principles required for successful
      risk assessment, risk management, and risk communication. Risk management will
      continue to be a balancing act of competing priorities and needs. Flexibility and
      good judgement are ultimately the key to successfully making appropriate risk
      decisions.

PMID- 14698954
TI  - Cellular origin of ionizing radiation-induced NF-kappaB activation in vivo and
      role of NF-kappaB in ionizing radiation-induced lymphocyte apoptosis.
AB  - PURPOSE: To investigate the cellular origin of ionizing radiation (IR)-induced NF
      kappaB activation in vivo and the role of NF-kappaB in IR-induced lymphocyte
      apoptosis. MATERIALS AND METHODS: NF-kappaB activities were analysed by gel
      shift/supershift assay in isolated murine T- and B-cells, macrophages (MPhi) and
      tissues from normal and T- and B-cell-deficient Rag1 mice with or without
      exposure to IR. IR-induced lymphocyte apoptosis was determined by analysis of
      3,3'-dihexyloxacarbocyanine iodide (DiOC(6)) uptake, annexin-V staining and the
      sub-G0/1 population, or by TUNEL assay. RESULTS: The results showed that IR
      activated NF-kappaB in lymphocytes, including both T- and B-cells, but failed to
      do so in MPhi. Furthermore, T- and B-cell-deficient Rag1 mice exposed to IR
      exhibited a significant reduction in NF-kappaB activation as compared with normal
      mice. Although NF-kappaB1 (p50) gene knockout or NF-kappaB decoy oligonucleotide
      treatment specifically inhibited IR-induced lymphocyte NF-kappaB activation, they
      had no significant effect on IR-induced lymphocyte apoptosis. CONCLUSIONS: This
      finding suggests that lymphocytes are the main cellular origin of IR-induced NF
      kappaB activation in vivo. However, NF-kappaB activation has no significant
      effect on IR-induced lymphocyte apoptosis.

PMID- 14698956
TI  - Inhibition of cyclooxygenase-2 with NS-398 and the prevention of radiation
      induced transformation, micronuclei formation and clonogenic cell death in C3H
      10T1/2 cells.
AB  - PURPOSE: Abnormally high levels of the cyclooxygenase (COX)-2 isozyme as well as
      the prostaglandin metabolites produced by the COX pathway have been observed in a
      variety of malignancies, including cancers of the skin, pancreas, colon, breast,
      cervix, prostate, and head and neck. Furthermore, exogenous genotoxic agents,
      including ionizing radiation (IR), have been shown to induce cellular
      transformation and to elevate COX-2 activity, whereas exposure to agents that
      specifically inhibit COX-2 activity have been shown to inhibit transformation.
      These data suggest a possible role of COX-2 both in IR-mediated cellular
      transformation processes and cell death. MATERIALS AND METHODS: C3H 10T1/2 and/or
      HeLa cells were treated with N-[2-(cyclohexyloxy)-4-nitrophenyl]
      methanesulfonamide (NS-398) and/or exposed to IR. Following treatment, cells were
      assayed for neoplastic transformation, clonogenicity, growth rates, cell cycle
      distribution, micronuclei formation and DNA damage by established methodologies.
      Statistical tests were performed on data as described. RESULTS: In the present
      study, experiments in normal murine fibroblast C3H 10T1/2 cells demonstrated that
      the chemical inhibition of COX-2 activity with moderate doses of NS-398 abrogated
      IR-induced transformation events by fourfold and protected irradiated C3H 10T1/2
      cells from clonogenic cell death. Considering that these doses of NS-398 had no
      significant effect on cellular proliferation or cell cycle distribution in C3H
      10T1/2 cells, the results suggest that inhibition of COX-2 either increases DNA
      repair or prevents the accumulation of DNA damage. In supplemental experiments,
      treatment with NS-398 caused a 1.5-fold reduction in IR-induced micronuclei
      formation and a significant decrease in DNA damage. CONCLUSIONS: These results
      suggest a role for COX-2 inhibitors in the normal tissue response to IR when
      administered at therapeutically achievable doses and therefore may have clinical
      implications for radiation oncology patients in the prevention of IR-induced
      malignancy.

PMID- 14698955
TI  - Sustained elevation of NF-kappaB DNA binding activity in radiation-induced lung
      damage in rats.
AB  - PURPOSE: To characterize the cellular distribution and DNA binding activity of
      the nuclear factor kappaB (NF-KappaB) in a model of radiation-induced lung damage
      in the rat. MATERIAL AND METHODS: The right lung of Fischer rats was irradiated
      with a single dose of 20 Gy. The cellular distributions of NF-KappaB proteins and
      mRNA were detected with immunohistochemistry and in-situ hybridization
      respectively. The DNA binding activity of NF-KappaB, nuclear and cytoplasmic
      levels of NF-KappaB proteins, and kinase activity towards IkappaBalpha
      (IKappaBAlpha) were determined using electrophoretic mobility shift assays
      (EMSA), Western blots and kinase assays, respectively. The mRNA level of
      interleukin 6 (IL-6) was determined using quantitative room temperature
      polymerase chain reaction. RESULTS: There was a continuous elevation of NF-KappaB
      DNA binding activity in the rat lung after ionizing irradiation over 6 months.
      The irradiated lung tissue exhibited an increased kinase activity towards
      IKappaBAlpha and a selective loss of nuclear IKappaBAlpha. The NF-KappaB-DNA
      binding complex switched from p50-p65 heterodimers in normal lung tissue to p50
      homodimers in irradiated lung tissue. The increased level of IL-6 mRNA suggests
      transcriptional activation of NF-KappaB-dependent genes in the irradiated rat
      lung. CONCLUSIONS: The DNA binding activity of NF-KappaB is continuously
      activated after irradiation of the rat lung by loss of nuclear IKappaBAlpha. This
      might play a role in sustaining chronic inflammation and hyperproliferation of
      mesenchymal cells after irradiation.

PMID- 14698957
TI  - Effects of multiple doses of ionizing radiation on cytokine expression in rat and
      human cells.
AB  - PURPOSE: To determine the effect of daily fractionated irradiation on the
      expression of growth factors and cytokines in different cardiac and vascular cell
      types. MATERIALS AND METHODS: Cell cultures of rat cardiac myocytes, fibroblasts,
      a rat cardiac microvascular endothelial cell line and human artery endothelial
      cells were irradiated with doses of 2 Gy, given daily during 5 consecutive days.
      Twenty-four hours after each fraction, gene expression was determined by
      competitive or semiquantitative polymerase chain reaction. Protein secretion into
      culture media was determined by enzyme-linked immunoabsorbant assay. RESULTS: Of
      all investigated mRNA levels, transforming growth factor (TGF)-ss1 and fibroblast
      growth factor (FGF)-2 were slightly upregulated in the rat cardiac endothelial
      cell line after irradiation. TGF-ss1 protein secretion by these cells was
      slightly, but non-significantly, elevated. Interleukin 1ss protein levels in
      myocyte culture media were decreased in control cultures at days 3 and 4 compared
      with day 2. No significant changes were observed in expression of FGF-2 in either
      of the four cell types. Moreover, no changes were observed in gene expression of
      platelet-derived growth factors A, B and interleukin 8 in the human artery
      endothelial cells. CONCLUSIONS: Fractionated irradiation leads to minor changes
      in the expression of specific cytokines in cardiac myocytes, fibroblasts and
      endothelial cells.

PMID- 14698958
TI  - Time- and dose-dependent changes of intracellular cytokine and cytokine receptor
      profile of Ewing tumour subpopulations under the influence of ionizing radiation.
AB  - PURPOSE: Cytokines and their corresponding cell surface receptors are involved in
      intercellular signalling pathways and in the radioresistance of normal and
      malignant cells. The aim was the characterization of the expression of
      intracellular cytokines, their receptors and apoptosis-associated markers under
      the influence of radiation. MATERIAL AND METHODS: Two Ewing tumours were
      characterized in vitro before and 4, 24 and 72 h after radiation with 5 and 10
      Gy, and in vivo 4, 6 and 15 days after radiation with 5 and 30 Gy by five
      parameter flow cytometry. Direct fluorescence-conjugated antibodies directed
      against intracellular cytokines (interferon-gamma, tumour necrosis factor [TNF]
      alpha, interleukin 1) and their receptors (CD119, CD120a, CD121a) were used.
      Annexin V and 7-amino-actinomycin D were used to identify radiation-induced
      apoptosis. RESULTS: Inter- and intra-individual heterogeneities were identified
      by the expression of cytokine receptors and the intracellular cytokine profile
      before radiation. Time- and dose-dependent up-regulation of the cytokines TNF
      alpha and interleukin 1 were found in vitro. In vivo, an up-regulation of CD120a
      and CD121a was detectable on tumour cell subpopulations. For interferon-gamma and
      CD119, no changes were seen. CONCLUSIONS: The observed radiation-induced changes
      of cytokine and receptor profile are an indication for complex intercellular
      interactions in view of radioresistance-associated mechanisms between cell
      populations within one individual tumour. The observed heterogeneous response on
      radiation might have therapeutic implications for an individualized therapy based
      on combined radiation and cytokine modulation, defined by flow cytometric
      characterization of markers potentially informative for radioresistance.

PMID- 14698959
TI  - Mutagenic effect of low energy neutrons on human chromosome 11.
AB  - PURPOSE: The shape of the dose-effect curve for neutrons, i.e. the question as to
      whether the curve is linear or supralinear in the low-dose region, is still not
      clear. Therefore, the mutagenic effect of very low doses of low-energy neutrons
      was determined. MATERIALS AND METHODS: Human-hamster hybrid A(L) cells contain
      human chromosome 11, which expresses the membrane protein CD59. This membrane
      protein can be detected immunologically and quantified by flow cytometry. The
      A(L) cells were irradiated with neutrons of 0.565, 2.5 or 14.8 MeV and the
      results were compared with those after 200 kVp X-rays. Before irradiation, cells
      spontaneously mutated in the CD59 gene were removed by magnetic cell sorting
      (MACS). RESULTS: The relative biological effectiveness (RBE) for CD59 mutation
      induction was 19.8 (+/-2.7) for 0.565 MeV, 10.2 (+/-1.9) for 2.5 MeV, and 10.2
      (+/-1.6) for 14.8 MeV neutrons. Linear mutation responses were obtained with all
      radiations except for 14.8 MeV neutrons where a supralinear curve may be a better
      fit. The deletion spectrum of mutated cell clones showed 29 Mbp deletions on
      average after irradiation with 0.069 Gy of 0.565 MeV neutrons. This scale of
      deletions is similar to that after 3 Gy 100 kV X-rays (=34 Mbp). For 50% cell
      survival, the RBE of the neutrons was 11 compared with 200 kV X-rays.
      CONCLUSIONS: Neutrons of low energies (0.565 or 2.5 MeV) produce a linear dose
      response for mutation in the tested dose range of 0.015-0.15 Gy. The neutron
      curve of 14.8 MeV can be approximated by a curvilinear or linear function.

PMID- 14698960
TI  - Inhibition of UV-induced G1 arrest by exposure to 50 Hz magnetic fields in repair
      proficient and -deficient yeast strains.
AB  - PURPOSE: To assess the possibility that extremely low frequency (ELF) magnetic
      fields obstruct the damage repair process, the gene conversion frequency and cell
      cycle kinetics in a DNA repair-proficient and nucleotide excision repair (NER)
      deficient strain of diploid yeast Saccharomyces cerevisiae. MATERIALS AND
      METHODS: DNA repair- or NER-deficient cells were irradiated with sublethal doses
      of ultraviolet light (UV) radiation followed by exposure to 50 Hz magnetic fields
      up to 30 mT for 48 h. After exposure, colony-forming ability was scored as
      revertants in which gene conversion had restored the functional allele of the
      ARG4 gene conversion hotspot. Cell cycle analysis was performed using flow
      cytometry. RESULTS: Gene conversion rate was increased by the combined exposure
      in DNA repair-proficient cells, whereas it remained unchanged between UV alone
      and the combined exposure in NER-deficient cells. The UV-induced G1 arrest was
      inhibited by exposure to 30 mT ELF magnetic fields in both repair-proficient and 
      deficient cells. CONCLUSIONS: The results suggest that exposure to high-density
      (30 mT) ELF magnetic fields decreases the efficiency of NER by suppressing G1
      arrest, which in turn led to enhancement of the UV-induced gene conversion.

PMID- 14698962
TI  - The urea transporter (UT) family: bioinformatic analyses leading to structural,
      functional, and evolutionary predictions.
AB  - We have identified all currently sequenced members of the urea transporter (UT)
      family (TC #1.A.28). Homologues occur exclusively in vertebrate animals and
      bacteria but not in other eukaryotic kingdoms or archaea. Sequence, structural,
      and phylogenetic analyses reveal conserved regions and residues and suggest that
      a primordial 5 transmembrane helical segment (TMS)-encoding genetic element
      duplicated to give a 10 TMS-encoding element early during evolutionary history,
      at about the time when eukaryotes diverged from prokaryotes. Two well-conserved,
      strongly amphipathic, putative alpha-helices that precede both 5 TMS repeat
      elements are predicted to be of structural, functional, or biogenic significance.
      A second duplication event (or a gene fusion event) occurred during development
      of the vertebrate lineage, giving rise to 20 TMS mammalian homologues. The
      results suggest that vertebrates acquired UT genetic information from bacteria
      only once and that all current orthologues and paralogues in the animal kingdom
      arose from this one primordial system.

PMID- 14698963
TI  - Stoichiometry of recombinant heteromeric glycine receptors revealed by a pore
      lining region point mutation.
AB  - Heteromeric glycine receptors mediate synaptic inhibition in the caudal areas of
      the adult mammalian central nervous system (CNS). These channels resemble other
      receptors in the nicotinic superfamily in that they are pentamers, but may differ
      in that they contain alpha and beta subunits in a 3:2 rather than a 2:3 ratio.
      Evidence in favor of a 3alpha:2beta stoichiometry of heteromeric glycine
      receptors comes from biochemical data and from the expression of chimeric
      subunits. We investigated this question using a potentially more direct approach
      and mutated the highly conserved hydrophobic residues in the middle (position 9')
      of the pore-lining domain. This mutation increases agonist potency in all
      channels in the nicotinic superfamily and its effects are in first approximation
      proportional to the number of mutant subunit incorporated into the receptor. We
      expressed in HEK 293 cells wild-type glycine alpha1beta receptors or receptors
      bearing the 9' mutation on either the alpha or the beta subunit, using an
      alpha:beta plasmid ratio of 1:40 in the transfection. This resulted in negligible
      levels of contamination by homomeric alpha1 receptors, as proven by low
      picrotoxin potency and by the extreme rarity of high conductances in single
      channel recording. Our data show that the effects of the 9' mutation on the
      receptor sensitivity to glycine were more marked when the alpha subunit bore the
      mutation. The magnitude of the leftward shift in the agonist dose-response curve
      for the two mutant combinations was in agreement with a subunit stoichiometry of
      3alpha:2beta.

PMID- 14698964
TI  - Phylogenomic analysis and evolution of the potassium channel gene family.
AB  - Potassium channels govern the permeability of cells to potassium ions, thereby
      controlling the membrane potential. In metazoa, potassium channels are encoded by
      a large, diverse gene family. Previous analyses of this gene family have focused
      on its diversity in mammals. Here we have pursued a more comprehensive study in
      Caenorhabditis elegans, Drosophila melanogaster, and mammalian genomes. The
      investigation revealed 164 potassium channel encoding genes in C. elegans, D.
      melanogaster, and mammals, classified into seven conserved families, which we
      applied to phylogenetic analysis. The trees are discussed in relation to the
      assignment of orthologous relationships between genes and vertebrate genome
      duplication.

PMID- 14698965
TI  - Melatonin for the treatment of disorders in circadian rhythm and sleep: could it
      form a basis for medication?
AB  - The various aspects of the existing knowledge on the physiological role of
      melatonin and its mode of action in circadian rhythms and sleep are presented.
      Furthermore, the possibility of its clinical application in maintenance of sleep
      under regular and environmental changes is discussed.

PMID- 14698966
TI  - Biophysical properties of Kv3.1 channels in SH-SY5Y human neuroblastoma cells.
AB  - Biophysical properties of delayed rectifier K channels in the human neuroblastoma
      SH-SY5Y were established using patch clamp recordings. The whole cell K+
      conductance activated at membrane potentials positive to -20 mV. The midpoint of
      current activation was 9.6 +/- 5.1 mV, the equivalent charge was 3.7 +/-.6. Whole
      cell currents inactivated slightly with time constants of 700 ms and 5 s. The K+
      currents were sensitive to micromolar concentrations of TEA and 4-aminopyridine.
      RT-PCR experiments amplified a cDNA fragment specific for human Kv3.1 channels.
      Activation gating parameters in outside-out patches were shifted by approximately
      14 mV in the hyperpolarizing direction.

PMID- 14698968
TI  - Proceedings of the American College of Endocrinology Insulin Resistance Syndrome
      Conference. Washington, DC, USA. August 25-26, 2002.

PMID- 14698969
TI  - Insulin resistance syndrome: the public health challenge.

PMID- 14698970
TI  - Insulin resistance syndrome: implications for the Latino/Hispanic population.

PMID- 14698971
TI  - Insulin resistance syndrome: implications for the African American population.

PMID- 14698973
TI  - Genetics of insulin resistance syndrome.

PMID- 14698972
TI  - Insulin resistance syndrome: implications for the Asian American population.

PMID- 14698974
TI  - Insulin signaling and the link to endothelial dysfunction.

PMID- 14698975
TI  - Analysis of data on insulin resistance from the European group for the study of
      insulin resistance: focus on obesity and hypertension.

PMID- 14698976
TI  - Insulin resistance syndrome and the prothrombotic state: a Framingham
      perspective.

PMID- 14698977
TI  - The link between insulin resistance syndrome and inflammatory markers.

PMID- 14698978
TI  - Insulin resistance syndrome and obesity.

PMID- 14698979
TI  - Insulin resistance syndrome and dyslipidemia.

PMID- 14698980
TI  - Insulin resistance syndrome and type 2 diabetes.

PMID- 14698981
TI  - Insulin resistance syndrome: a pediatric perspective.

PMID- 14698982
TI  - Adolescents, polycystic ovary syndrome, and insulin resistance syndrome.

PMID- 14698983
TI  - Insulin resistance syndrome and polycystic ovary syndrome.

PMID- 14698984
TI  - Insulin resistance syndrome and gestational diabetes.

PMID- 14698985
TI  - Insulin resistance syndrome and nonalcoholic fatty liver disease.

PMID- 14698986
TI  - Therapeutic lifestyle changes in the management of obesity.

PMID- 14698987
TI  - Treatment of the insulin resistance syndrome.

PMID- 14698988
TI  - Emerging concepts in management of the insulin resistance syndrome.

PMID- 14698989
TI  - Spatial distribution of hypoxic pulmonary vasoconstriction in the supine pig.
AB  - Hypoxic pulmonary vasoconstriction (HPV) serves to maintain optimal gas exchange
      by decreasing perfusion to hypoxic regions. However, global hypoxia and
      nonuniform HPV may result in overperfusion of poorly constricted regions leading
      to local edema seen in high-altitude pulmonary edema. To quantify the spatial
      distribution of HPV and its response to regional Po2 (Pr(O2)) among small lung
      regions, five pigs were anesthetized and mechanically ventilated in the supine
      posture. The animals were ventilated with an inspired O2 fraction (Fi(O2)) of
      0.50 and 0.21 and then (in random order) 0.15, 0.12, and 0.09. Regional blood
      flow (Q) and alveolar ventilation (Va) were measured by using intravenous
      infusion of 15 microm and inhalation of 1-microm fluorescent microspheres,
      respectively. Pr(O2) was calculated for each piece at each Fi(O2). Lung pieces
      differed in their Q response to hypoxia in a manner related to their initial Va/Q
      with Fi(O2) = 0.21. Reducing Fi(O2) < 0.15 decreased Q to the initially high Va/Q
      (higher Pr(O2)) regions and forced Q into the low Va/Q (dorsal-caudal) regions.
      Resistance increased in most lung pieces as Pr(O2) decreased, reaching a maximum
      resistance when Pr(O2) is between 40 and 50 Torr. Local resistance decreased at
      PrO2 < 40 Torr. Pieces were statistically clustered with respect to their
      relative Q response pattern to each Fi(O2). Some clusters were shown to be
      spatially organized. We conclude that HPV is spatially heterogeneous. The
      heterogeneity of Q response may be related, in part, to the heterogeneity of
      baseline Va/Q.

PMID- 14698990
TI  - Exercise training attenuated the PKB and GSK-3 dephosphorylation in the
      myocardium of ZDF rats.
AB  - Cardiac dysfunction is a severe secondary effect of Type 2 diabetes. Recruitment
      of the protein kinase B/glycogen synthase kinase-3 pathway represents an integral
      event in glucose homeostasis, albeit its regulation in the diabetic heart remains
      undefined. Thus the following study tested the hypothesis that the regulation of
      protein kinase B/glycogen synthase kinase-3 was altered in the myocardium of the
      Zucker diabetic fatty rat. Second, exercise has been shown to improve glucose
      homeostasis, and, in this regard, the effect of swimming training on the
      regulation of protein kinase B/glycogen synthase kinase-3 in the diabetic rat
      heart was examined. In the sedentary Zucker diabetic fatty rats, glucose levels
      were elevated, and cardiac glycogen content increased, compared with wild type. A
      13-wk swimming regimen significantly reduced plasma glucose levels and cardiac
      glycogen content and partially normalized protein kinase B-serine473, protein
      kinase B-threonine308, and glycogen synthase kinase-3alpha phosphorylation in
      Zucker diabetic fatty rats. In conclusion, hyperglycemia and increased cardiac
      glycogen content in the Zucker diabetic fatty rats were associated with
      dysregulation of protein kinase B/glycogen synthase kinase-3 phosphorylation.
      These anomalies in the Zucker diabetic fatty rat were partially normalized with
      swimming. These data support the premise that exercise training may protect the
      heart against the deleterious consequences of diabetes.

PMID- 14698991
TI  - Fluorescent microsphere method is suitable for chronic bone blood flow
      measurement: a long-term study after meniscectomy in rabbits.
AB  - The fluorescent microsphere (FM) method is considered a reliable technique to
      determine regional bone blood flow (RBBF) in acute experiments. In this study, we
      verified the accuracy and validity of this technique for measurement of RBBF in a
      long-term experiment and examined RBBF after meniscectomy. Twenty-four
      anesthetized female New Zealand white rabbits (3 groups, each n = 8) received
      consecutive left ventricular injections of FM in defined time intervals after
      meniscectomy: group 1 from preoperation to 3 wk postoperation; group 2 from 3 to
      7 wk postoperation; and group 3 from 7 to 11 wk postoperation. To test the
      precision of the FM method, two FM species were injected simultaneously at the
      first and last measurement. After the experiment, humeri, femora, tibiae, and
      reference organs (kidney, lung, brain) were removed and dissected according to
      standardized protocols. Fluorescence was determined in each reference blood and
      tissue sample, and blood flow values were calculated. Blood flow in kidney, lung,
      and brain revealed no significant difference between right and left side and
      remained unchanged during the observation period, thus excluding errors due to
      shunting and dislodging of spheres in our experiments. Comparison of relative
      bone blood flow values obtained by simultaneously injected FM showed an excellent
      correlation at the first and last injection, indicating valid RBBF measurements
      in long-term experiments. We found a significant increase in RBBF 3 wk after
      meniscectomy in the right tibial condyles compared with the nonoperated left
      side. Similar changes were found in the femoral condyles. RBBF in other regions
      of tibia, femur, and humerus revealed no significant differences between right-
      and left-sided bone samples of the same region. Our results demonstrate that the
      FM method is valid for measuring RBBF in long-term experiments. In addition, we
      were able to demonstrate that meniscectomy leads to an increase in RBBF in the
      tibial condyles at a very early stage. This increase might be caused by stress
      induced alterations of the subchondral bone.

PMID- 14698992
TI  - Cooling vest worn during active warm-up improves 5-km run performance in the
      heat.
AB  - We investigated whether a cooling vest worn during an active warm-up enhances 5
      km run time in the heat. Seventeen competitive runners (9 men, maximal oxygen
      uptake = 66.7 +/- 5.9 ml x kg(-1) x min(-1); 8 women, maximal oxygen uptake =
      58.0 +/- 3.2 ml x kg(-1) x min(-1)) completed two simulated 5-km runs on a
      treadmill after a 38-min active warm-up during which they wore either a T-shirt
      (C) or a vest filled with ice (V) in a hot, humid environment (32 degrees C, 50%
      relative humidity). Wearing the cooling vest during warm-up significantly (P <
      0.05) blunted increases in body temperature, heart rate (HR), and perception of
      thermal discomfort during warm-up compared with control. At the start of the 5-km
      run, esophageal, rectal, mean skin, and mean body temperatures averaged 0.3, 0.2,
      1.8, and 0.4 degrees C lower; HR averaged 11 beats/min lower; and perception of
      thermal discomfort (5-point scale) averaged 0.6 point lower in V than C. Most of
      these differences were eliminated during the first 3.2 km of the run, and these
      variables were not different at the end. The 5-km run time was significantly
      lower (P < 0.05) by 13 s in V than C, with a faster pace most evident during the
      last two-thirds of the run. We conclude that a cooling vest worn during active
      warm-up by track athletes enhances 5-km run performance in the heat. Reduced
      thermal and cardiovascular strain and perception of thermal discomfort in the
      early portion of the run appear to permit a faster pace later in the run.

PMID- 14698993
TI  - Influence of fingertip contact on illusory arm movements.
AB  - Recent evidence suggests that reaching movements are more accurate when end point
      contact occurs, suggesting that fingertip contact contributes to a final
      estimation of arm position. In the present study we tested two hypotheses: 1).
      that fingertip contact influences illusions of arm movement produced by muscle
      vibration and 2). that this influence depends on the a priori context of the
      stability of the contact surface. Subjects sat with their elbows on a table and
      eyes closed. They demonstrated the perceived orientation of the left (cue) arm by
      mirroring the location with the right (report) arm. We manipulated deep
      proprioceptive cues by vibrating the left biceps brachia, causing illusions of
      elbow extension, and tested whether these illusions were altered when the
      fingertip remained in contact with a stable external surface. The context at this
      point represents a prior assumption that the external contact surface is stable.
      Midway through the experiment, the context was changed by challenging the prior
      assumption that the contact surface was stable by demonstrating that it could
      move. Unbeknownst to the subject, the external contact surface remained stable
      during data collection throughout the experiment. As expected, without tactile
      cues, biceps vibration caused illusory elbow extension. Conditions with fingertip
      contact and biceps vibration in the stable context demonstrated that contact
      largely eliminated the overestimation of cue arm elbow angle. However, in the
      context of a possibly unstable (movable) contact surface, the reports of elbow
      extension returned. Thus a priori notions about the stability context of an
      external contact surface influence how this tactile cue is integrated with
      proprioceptive sensory modalities to generate an estimate of arm location in
      space. These findings support the notion that tactile cues are used to calibrate
      proprioception against external spatial frameworks.

PMID- 14698994
TI  - Ionotropic excitatory amino acid receptors in pre-Botzinger complex play a
      modulatory role in hypoxia-induced gasping in vivo.
AB  - Activation of ionotropic excitatory amino acid (EAA) receptors in pre-Botzinger
      complex (pre-BotC) not only influences the eupneic pattern of phrenic motor
      output but also modifies hypoxia-induced gasping in vivo by increasing gasp
      frequency. Although ionotropic EAA receptor activation in this region appears to
      be required for the generation of eupneic breathing, it remains to be determined
      whether similar activation is necessary for the production and/or expression of
      hypoxia-induced gasping. Therefore, we examined the effects of severe brain
      hypoxia before and after blockade of ionotropic EAA receptors in the pre-BotC in
      eight chloralose-anesthetized, deafferented, mechanically ventilated cats. In
      each experiment, before blockade of ionotropic EAA receptors in the pre-BotC,
      severe brain hypoxia (6% O2 in a balance of N2 for 3-6 min) produced gasping.
      Although bilateral microinjection of the broad-spectrum ionotropic EAA receptor
      antagonist kynurenic acid (20-100 mM; 40 nl) into the pre-BotC eliminated basal
      phrenic nerve discharge, severe brain hypoxia still produced gasping. Under these
      conditions, however, the onset latency to gasping was increased (P < 0.05), the
      number of gasps was reduced for the same duration of hypoxic gas exposure (P <
      0.05), the duration of gasps was prolonged (P < 0.05), and the duration between
      gasps was increased (P < 0.05). These findings demonstrate that hypoxia-induced
      gasping in vivo does not require activation of ionotropic EAA receptors in the
      pre-BotC, but ionotropic EAA receptor activation in this region may modify the
      expression of the hypoxia-induced response. The present findings also provide
      additional support for the pre-BotC as the primary locus of respiratory rhythm
      generation.

PMID- 14698995
TI  - Physiological and inflammatory response to instillation of an oxidized surfactant
      in a rat model of surfactant deficiency.
AB  - Pulmonary surfactant is a mixture of phospholipids ( approximately 90%) and
      surfactant-associated proteins (SPs) ( approximately 10%) that stabilize the lung
      by reducing the surface tension. One proposed mechanism by which surfactant is
      altered during acute lung injury is via direct oxidative damage to surfactant. In
      vitro studies have revealed that the surface activity of oxidized surfactant was
      impaired and that this effect could be overcome by adding SP-A. On the basis of
      this information, we hypothesized that animals receiving oxidized surfactant
      preparations would exhibit an inferior physiological and inflammatory response
      and that the addition of SP-A to the oxidized preparations would ameliorate this
      response. To test this hypothesis, mechanically ventilated, surfactant-deficient
      rats were administered either bovine lipid extract surfactant (BLES) or in vitro
      oxidized BLES of three doses: 10 mg/kg, 50 mg/kg, or 10 mg/kg + SP-A. When
      instilled with 10 mg/kg normal surfactant, the rats had a significantly superior
      arterial Po2 responses compared with the rats receiving oxidized surfactant.
      Interestingly, increasing the dose five times mitigated this physiological
      effect, and the addition of SP-A to the surfactant preparation had little impact
      on improving oxygenation. There were no differences in alveolar surfactant pools
      and the indexes of pulmonary inflammation between the 10 mg/kg dose groups, nor
      was there any differences observed between either of the groups supplemented with
      SP-A. However, there was significantly more surfactant and more inflammatory
      cytokines in the 50 mg/kg oxidized BLES group compared with the 50 mg/kg BLES
      group. We conclude that instillation of an in vitro oxidized surfactant causes an
      inferior physiological response in a surfactant-deficient rat.

PMID- 14698996
TI  - Kallikrein gene transfer protects against ischemic stroke by promoting glial cell
      migration and inhibiting apoptosis.
AB  - Kallikrein/kinin has been shown to protect against ischemia/reperfusion-induced
      myocardial infarction and apoptosis. In the present study, we examined the
      potential neuroprotective action of kallikrein gene transfer in cerebral
      ischemia. Adult, male Sprague-Dawley rats were subjected to a 1-hour occlusion of
      the middle cerebral artery followed by intracerebroventricular injection of
      adenovirus harboring either the human tissue kallikrein gene or the luciferase
      gene. Kallikrein gene transfer significantly reduced ischemia-induced locomotor
      deficit scores and cerebral infarction after cerebral ischemia injury. Expression
      of recombinant human tissue kallikrein was identified and localized in
      monocytes/macrophages of rat ischemic brain by double immunostaining.
      Morphological analyses showed that kallikrein gene transfer enhanced the survival
      and migration of glial cells into the ischemic penumbra and core, as identified
      by immunostaining with glial fibrillary acidic protein. Cerebral ischemia
      markedly increased apoptotic cells, and kallikrein gene delivery reduced
      apoptosis to near-normal levels as seen in sham control rats. In primary cultured
      glial cells, kinin stimulated cell migration but inhibited hypoxia/reoxygenation
      induced apoptosis in a dose-dependent manner. The effects of kinin on both
      migration and apoptosis were abolished by icatibant, a bradykinin B2 receptor
      antagonist. Enhanced cell survival after kallikrein gene transfer occurred in
      conjunction with markedly increased cerebral nitric oxide levels and phospho-Akt
      and Bcl-2 levels but reduced caspase-3 activation, NAD(P)H oxidase activity, and
      superoxide production. These results indicate that kallikrein gene transfer
      provides neuroprotection against cerebral ischemia injury by enhancing glial cell
      survival and migration and inhibiting apoptosis through suppression of oxidative
      stress and activation of the Akt-Bcl-2 signaling pathway.

PMID- 14698997
TI  - Evidence for a causal role of the renin-angiotensin system in vascular
      dysfunction associated with insulin resistance.
AB  - Excess production of superoxide anion in response to angiotensin II plays a
      central role in the transduction of signal molecules and the regulation of
      vascular tone. We examined the ability of insulin resistance to stimulate
      superoxide anion production and investigated the identity of the oxidases
      responsible for its production. Rats were fed diets containing 60% fructose
      (fructose-fed rats) or 60% starch (control rats) for 8 weeks. In aortic
      homogenates from fructose-fed rats, the superoxide anion generated in response to
      NAD(P)H was more than 2-fold higher than that of control rats. Pretreatment of
      the aorta from fructose-fed rats with inhibitors of NADPH oxidase significantly
      reduced superoxide anion production. In the isolated aorta, contraction induced
      by angiotensin II was more potent in fructose-fed rats compared with control
      rats. Losartan normalized blood pressure, NAD(P)H oxidase activity, endothelial
      function, and angiotensin II-induced vasoconstriction in fructose-fed rats. To
      elucidate the molecular mechanisms of the enhanced constrictor response to
      angiotensin II, expressions of angiotensin II receptor and subunits of NADPH
      oxidase were examined with the use of angiotensin II type 1a receptor knockout
      (AT1a KO) mice. Expression of AT1a receptor mRNA was enhanced in fructose-fed
      mice, whereas expression of either AT1b or AT2 was unaltered. In addition,
      protein expression of each subunit of NADPH oxidase was increased in fructose-fed
      mice, whereas the expression was significantly decreased in fructose-fed AT1a KO
      mice. The novel observation of insulin resistance-induced upregulation of AT1
      receptor expression could explain the association of insulin resistance with
      endothelial dysfunction and hypertension.

PMID- 14698998
TI  - Nitric oxide synthesis inhibition promotes renal production of carbon monoxide.
AB  - We tested the hypothesis that the status of NO synthesis influences the renal
      heme-heme oxygenase system. Studies were conducted in untreated rats and rats
      treated with the NO synthesis inhibitor N(G)-nitro-L-arginine methyl ester for 2
      days. Treated and untreated rats were contrasted in terms of renal expression of
      heme oxygenase-1 and -2, renal carbon monoxide (CO)-generating activity, and
      urinary CO concentration and excretion rate. Heme oxygenase-1 and -2 proteins
      were similarly expressed in the kidneys of untreated and treated rats. In
      contrast, the NADPH-dependent component of the CO-generating activity of renal
      homogenates incubated with heme (a measure of heme oxygenase activity) was higher
      (P<0.05) in kidneys from rats treated with the NO synthesis inhibitor relative to
      corresponding data in untreated rats (1015+/-95 versus 379+/-111 pmol CO/mg per
      hour). Similarly, relative to corresponding data in untreated rats, rats treated
      with the NO synthesis inhibitor displayed increased (P<0.05) urinary CO
      concentration (920+/-174 versus 2286+/-472 pmol/mL) and urinary CO excretion
      (4.7+/-0.4 versus 14.3+/-2.7 pmol/min). This study demonstrates that NO synthesis
      inhibition upregulates the urinary concentration and excretion rate of CO, and
      the HO-dependent generation of CO by renal homogenates, without affecting the
      expression of renal heme oxygenase isoforms. Our findings imply that endogenous
      NO is an inhibitory regulator of renal CO generation by HO.

PMID- 14698999
TI  - Increased central artery stiffness in impaired glucose metabolism and type 2
      diabetes: the Hoorn Study.
AB  - Impaired glucose metabolism (IGM) and type 2 diabetes (DM-2) are associated with
      high cardiovascular disease risk. Increases in peripheral and central artery
      stiffness may represent pathophysiologic pathways through which glucose tolerance
      status leads to cardiovascular disease. Peripheral artery stiffness increases
      with deteriorating glucose tolerance status, whereas this trend remains unclear
      for central artery stiffness. Therefore, we investigated the associations between
      glucose tolerance status and estimates of central arterial stiffness. We
      performed a population-based study of 619 individuals (normal glucose metabolism,
      n=261; IGM, n=170; and DM-2, n=188) and assessed central artery stiffness by
      measuring total systemic arterial compliance, aortic pressure augmentation index,
      and carotid-femoral transit time. After adjustment for sex, age, heart rate,
      height, body mass index, and mean arterial pressure, DM-2 was associated with
      decreased total systemic arterial compliance, increased aortic augmentation
      index, and decreased carotid-femoral transit time. IGM was borderline
      significantly associated with decreased total systemic arterial compliance.
      Respective regression coefficients (95% confidence intervals) for IGM and DM-2
      compared with normal glucose metabolism were -0.05 (-0.11 to 0.01) and -0.13 (
      0.19 to -0.07) mL/mm Hg for total systemic arterial compliance; 1.1 (-0.2 to 2.5)
      and 1.6 (0.2 to 3.0) percentage points for aortic augmentation index; and -0.85 (
      5.20 to 3.49) and -4.95 (-9.41 to -0.48) ms for carotid-femoral transit time. IGM
      and DM-2 are associated with increased central artery stiffness, which is more
      pronounced in DM-2. Deteriorating glucose tolerance is associated with increased
      central and peripheral arterial stiffness, which may partly explain why both DM-2
      and IGM are associated with increased cardiovascular risk.

PMID- 14699000
TI  - Pressure-independent effects of angiotensin II on hypertensive myocardial
      fibrosis.
AB  - Angiotensin II (Ang II) is implicated in the proinflammatory process in various
      disease situations. Thus, we sought to determine the role of Ang II in early
      inflammation-induced fibrosis of pressure-overloaded (PO) hearts. PO was induced
      by suprarenal aortic constriction (AC) at day 0 in male Wistar rats, and they
      were orally administered 0.1 mg/kg per day candesartan every day from day -7.
      This was the maximum dose of candesartan that did not change arterial pressure in
      hypertensive rats with AC (AC rats). In AC rats, cardiac angiotensin-converting
      enzyme (ACE) activity was transiently enhanced after day 1 and peaked at day 3,
      declining to lower levels by day 14, whereas serum ACE activity was not changed.
      In AC rats, PO induced early fibroinflammatory changes (monocyte chemoattractant
      factor [MCP]-1 and transforming growth factor [TGF]-beta expression, perivascular
      macrophage accumulation, and fibroblast proliferation), and thereafter, left
      ventricular hypertrophy developed, featuring myocyte hypertrophy, intramyocardial
      arterial wall thickening, and perivascular and interstitial fibroses. Candesartan
      suppressed the induction of MCP-1 and TGF-beta and reduced macrophage
      accumulation and fibroblast proliferation in PO hearts. Candesartan significantly
      prevented perivascular and interstitial fibrosis. However, candesartan did not
      affect myocyte hypertrophy and arterial wall thickening. In conclusion, a
      subdepressor dose of candesartan prevented the MCP-1-mediated inflammatory
      process and reactive myocardial fibrosis in PO hearts. Ang II might play a key
      role in reactive fibrosis in hypertensive hearts, independent of arterial
      pressure changes.

PMID- 14699001
TI  - Age-related reduction in estrogen receptor-mediated mechanisms of vascular
      relaxation in female spontaneously hypertensive rats.
AB  - Hypertension increases with aging, and changes in vascular estrogen receptors
      (ERs) may play a role in age-related hypertension in women. We tested whether age
      related increases in blood pressure in female spontaneously hypertensive rats
      (SHRs) are associated with reduction in amount and/or vascular relaxation effects
      of estrogen and ER. Arterial pressure and plasma estradiol were measured in adult
      (12 weeks) and aging (16 months) female SHRs, and thoracic aorta was isolated for
      measurement of active stress, 45Ca2+ influx, and ERs. Arterial pressure was
      greater and plasma estradiol was less in aging females than in adult females. In
      aorta of adult females, Western blots revealed alpha- and beta-ERs that were
      slightly reduced in aging rats. In endothelium-intact vascular strips,
      phenylephrine (Phe; 10(-5) mol/L) caused greater active stress in aging rats
      (9.3+/-0.2) than in adult rats (6.2+/-0.3x10(4) N/m2). 17beta-estradiol (E2)
      caused relaxation of Phe contraction and stimulation of vascular nitrite/nitrate
      production, which was reduced in aging rats. In endothelium-denuded strips, E2
      still caused relaxation of Phe contraction, which was smaller in aging rats than
      adult rats. KCl (51 mmol/L), which stimulates Ca2+ influx, produced greater
      active stress in aging rats (9.1+/-0.3) than in adult rats (5.9+/-0.2x10(4)
      N/m2). E2 caused relaxation of KCl contraction and inhibition of Phe- and KCl
      induced 45Ca2+ influx, which were reduced in aging rats. Thus, aging in female
      SHR is associated with reduction in ER-mediated NO production from endothelial
      cells and decrease in inhibitory effects of estrogen on Ca2+ entry mechanisms of
      smooth muscle contraction. The age-related decrease in ER-mediated vascular
      relaxation may explain the increased vascular contraction and arterial pressure
      associated with aging in females.

PMID- 14699002
TI  - Ganglionic action of angiotensin contributes to sympathetic activity in renin
      angiotensinogen transgenic mice.
AB  - In addition to central nervous system actions, angiotensin (Ang) II may increase
      sympathetic nerve activity (SNA) via a direct action on sympathetic ganglia. We
      hypothesized that sympathetic ganglionic actions of endogenous Ang II contribute
      to SNA in transgenic mice that overexpress renin and angiotensinogen (R+A+ mice).
      Renal SNA and arterial pressure were recorded in anesthetized R+A+ and littermate
      control mice before and after ganglionic blockade, and after additional blockade
      of angiotensin type 1 (AT1) receptors with losartan. Ganglionic blockade
      essentially abolished SNA in control mice, but only reduced SNA to 47+/-18% of
      baseline in R+A+ mice. The residual SNA remaining after ganglionic blockade in
      R+A+ mice was reduced from 47+/-18% to 8+/-6% of baseline by losartan (P<0.05).
      The sympathoinhibitory response to losartan was accompanied by an enhanced
      decrease in arterial pressure in R+A+ mice compared with that observed in control
      mice. AT1 receptor expression in sympathetic ganglia, as measured by real-time
      reverse transcription-polymerase chain reaction, was increased approximately 3
      fold in R+A+ versus control mice. The results demonstrate that, as anticipated,
      essentially all of the renal postganglionic SNA in control mice is driven by
      preganglionic input. The major new finding is that Ang II-evoked ganglionic
      activity accounts for approximately 40% of total SNA in R+A+ mice. The
      significant contribution of the direct ganglionic action of Ang II in R+A+ mice
      likely reflects both increased levels of Ang II and upregulation of AT1 receptors
      in sympathetic ganglia.

PMID- 14699004
TI  - Angiotensin-converting enzyme inhibitors and 3-hydroxy-3-methylglutaryl coenzyme
      A reductase in cardiac Syndrome X: role of superoxide dismutase activity.
AB  - BACKGROUND: Morbidity of patients with Syndrome X (SX; chest pain and normal
      coronary angiograms) is high and is associated with continuing episodes of chest
      pain and hospitalization. Impairment of microvascular endothelial function caused
      by increased oxidative stress has been suggested to be a mechanism of the
      disease. Superoxide dismutase (SOD) is the major antioxidant enzyme system of the
      vascular wall. This study sought to establish whether combination treatment with
      ACE inhibitors and statins reduces oxidative stress and improves quality of life
      of patients with cardiac SX. METHODS AND RESULTS: Forty-five patients with SX
      were randomly assigned to receive either a combination of ramipril (10 mg/d) and
      atorvastatin (40 mg/d) or placebo for 6 months. We determined the activity of
      extracellular SOD and its relation to flow-dependent endothelium-mediated
      dilation (FMD) and quality of life (exercise capacity and score with Seattle
      Angina Questionnaire [SAQ]) before and after treatment. After 6 months, patients
      with SX who received atorvastatin and ramipril had significantly reduced
      (P=0.001) SOD levels (188.1+/-29.6 U/mL). No significant changes were seen on
      placebo (262.9+/-48.8 U/mL). Reduction of SOD after therapy was negatively
      correlated with FMD (r=0.38; P=0.01) and positively with total cholesterol (r=
      0.56; P<0.001). At follow-up, patients taking atorvastatin and ramipril improved
      their quality of life both in terms of exercise duration (by 23.46%) and SAQ (by
      64.1%). CONCLUSIONS: Six months of therapy with atorvastatin and ramipril
      improves endothelial function and quality of life of patients with SX. Reduced
      SOD activity may reflect low superoxide anion production. Benefits of these drugs
      may be related to reduction of oxidative stress.

PMID- 14699005
TI  - Estradiol and progestins differentially modulate leukocyte infiltration after
      vascular injury.
AB  - BACKGROUND: Inflammation plays an important role in the response to endoluminal
      vascular injury. Estrogen (17beta-estradiol, E2) inhibits neointima formation in
      animal models, and the progestin medroxyprogesterone acetate (MPA) blocks this
      effect. This study tested the hypothesis that E2 inhibits the migration of
      inflammatory cells, particularly granulocytes, into the rat carotid arteries
      after acute endoluminal injury and that MPA blocks this effect. METHODS AND
      RESULTS: Ovariectomized rats were randomly divided into subgroups and treated
      with E2, MPA, E2+MPA, or vehicle and subjected to balloon injury of the right
      carotid artery. After 1, 3, or 7 days, rats were euthanized, and carotid arteries
      (injured and control) were analyzed for inflammatory cells by flow cytometry. At
      1 day, granulocytes (HIS48+ and CD45+), monocyte/macrophages (Mar1+ and CD45+),
      and T lymphocytes (CD3+ and CD45+) were increased 26-fold, 12-fold, and 3-fold,
      respectively, in injured compared with contralateral control arteries of vehicle
      treated rats. Granulocytes and monocyte/macrophages decreased markedly by 3 days.
      E2 reduced the granulocyte and monocyte/macrophage populations of injured vessels
      by approximately 50% and increased T lymphocytes. MPA had no independent effect
      on inflammatory cells but completely blocked the effect of E2.
      Immunohistochemical examination verified these findings and localized
      inflammatory cells to the adventitial and periadventitial domains of injured
      vessels. CONCLUSIONS: E2 may limit the neointimal response to endoluminal
      vascular injury, at least in part, by limiting leukocyte entry from
      adventitial/periadventitial tissues into injured vessels early in the injury
      response.

PMID- 14699006
TI  - Toll-like receptor 4 is involved in outward arterial remodeling.
AB  - BACKGROUND: Toll-like receptor 4 (Tlr4) is the receptor for exogenous
      lipopolysaccharides (LPS). Expression of endogenous Tlr4 ligands, heat shock
      protein 60 (Hsp60) and extra domain A of fibronectin, has been observed in
      arthritic and oncological specimens in which matrix turnover is an important
      feature. In atherosclerosis, outward remodeling is characterized by matrix
      turnover and a structural change in arterial circumference and is associated with
      a vulnerable plaque phenotype. Since Tlr4 ligands are expressed during matrix
      turnover, we hypothesized that Tlr4 is involved in arterial remodeling. METHODS
      AND RESULTS: In a femoral artery cuff model in the atherosclerotic ApoE3 (Leiden)
      transgenic mouse, Tlr4 activation by LPS stimulated plaque formation and
      subsequent outward arterial remodeling. With the use of the same model in wild
      type mice, neointima formation and outward remodeling occurred. In Tlr4-deficient
      mice, however, no outward arterial remodeling was observed independent of
      neointima formation. Carotid artery ligation in wild-type mice resulted in
      outward remodeling without neointima formation in the contralateral artery. This
      was associated with an increase in Tlr4 expression and EDA and Hsp60 mRNA levels.
      In contrast, outward remodeling was not observed after carotid ligation in Tlr4
      deficient mice. CONCLUSIONS: These findings provide genetic evidence that Tlr4 is
      involved in outward arterial remodeling, probably through upregulation of Tlr4
      and Tlr4 ligands.

PMID- 14699007
TI  - Exercise training reduces neointimal growth and stabilizes vascular lesions
      developing after injury in apolipoprotein e-deficient mice.
AB  - BACKGROUND: Population-based studies have shown that exercise reduces
      cardiovascular morbidity and mortality. However, it is unknown whether these
      effects are solely a result of risk factor modification or whether exercise
      directly affects the homeostasis of the vessel wall. METHODS AND RESULTS: We
      subjected 19-week-old apolipoprotein E (apoE)-knockout mice (apoE(-/-); n=25) to
      a 6-week training program on a motorized treadmill. The control group consisted
      of 17 sedentary mice. After 3 weeks in the program, training and sedentary mice
      underwent carotid artery injury with ferric chloride. Training was then resumed
      for another 3 weeks. Exercise did not change body weight or lipid levels in apoE(
      /-) mice but resulted in upregulated expression of nitric oxide synthase in the
      endothelium. Physical training did not significantly affect the thrombotic
      response to injury. However, morphometric analysis of vessels harvested 3 weeks
      after injury showed that neointima formation was reduced in the exercising group.
      This resulted in a lower intima/media ratio (0.29+/-0.03 versus 0.41+/-0.03 in
      sedentary mice; P=0.008) and less luminal stenosis (21+/-2.7% versus 33+/-2.3%;
      P=0.003). Importantly, exercise reduced the number of Mac-3-positive, oxidized
      LDL-containing macrophages in the vessel wall while increasing the content in
      collagen fibers (14.1+/-0.9% versus 4.8+/-0.8%; P<0.001). Plasminogen activator
      inhibitor-1, tissue factor, and fibrinogen were all significantly reduced in the
      lesions of trained mice. CONCLUSIONS: In the apoE(-/-) mouse, exercise training
      reduces neointimal growth and stabilizes vascular lesions after injury. These
      effects appear to be at least partly independent of changes in lipid levels or
      the initial thrombotic response to injury.

PMID- 14699008
TI  - Targeted overexpression of noncleavable and secreted forms of tumor necrosis
      factor provokes disparate cardiac phenotypes.
AB  - BACKGROUND: Recent studies suggest that posttranslation processing or "shedding"
      (ie, secretion) of tumor necrosis factor (TNF) by tumor necrosis factor-alpha
      converting enzyme (TACE) may contribute to the left ventricular (LV) remodeling
      that occurs in the failing human heart. METHODS AND RESULTS: To address the
      functional significance of TNF shedding, we generated lines of transgenic mice
      with targeted overexpression of secreted wild-type (MHCsTNF2) TNF and
      overexpression of a mutated noncleavable transmembrane form of TNF (MHCmTNF).
      Both lines of mice had overlapping levels of myocardial TNF protein; however, the
      phenotypes of the MHCsTNF2 and MHCmTNF mice were strikingly disparate. Whereas
      the MHCmTNF mice developed a concentric LV hypertrophy phenotype, the MHCsTNF2
      mice developed a dilated LV phenotype. The fibrillar collagen weave in MHCmTNF
      mice with concentric hypertrophy was characterized by thick collagen fibrils and
      increased collagen content, whereas the fibrillar collagen weave in the MHCsTNF2
      mice with LV dilation was characterized by a diminished collagen content.
      Inhibition of matrix metalloproteinases with a broad-based matrix
      metalloproteinase inhibitor prevented LV dilation in the MHCsTNF2 mice.
      CONCLUSIONS: These findings suggest that posttranslational processing of TNF, as
      opposed to TNF expression per se, is responsible for the adverse cardiac
      remodeling that occurs after sustained TNF overexpression.

PMID- 14699009
TI  - Preoperative partitioning of pulmonary vascular resistance correlates with early
      outcome after thromboendarterectomy for chronic thromboembolic pulmonary
      hypertension.
AB  - BACKGROUND: Pulmonary thromboendarterectomy (PTE) is the preferred treatment for
      chronic thromboembolic pulmonary hypertension (CTEPH), but persistent pulmonary
      hypertension after PTE, as a result of either inaccessible distal thrombotic
      material or coexistent intrinsic small-vessel disease, remains a major
      determinant of poor outcome. Conventional preoperative evaluation is unreliable
      in identifying patients at risk for persistent pulmonary hypertension or
      predicting postoperative hemodynamic outcome. We postulated that pulmonary
      arterial occlusion pressure waveform analysis, a technique that has been used for
      partitioning pulmonary vascular resistance, might identify CTEPH patients with
      significant distal, small-vessel disease. METHODS AND RESULTS: Twenty-six
      patients underwent preoperative right heart catheterization before PTE. Pulmonary
      artery occlusion waveform recordings were performed in triplicate. Postoperative
      hemodynamics after PTE were compared with preoperative partitioning of pulmonary
      vascular resistance derived from the occlusion data. Preoperative assessment of
      upstream resistance (Rup) correlated with both postoperative total pulmonary
      resistance index (R2=0.79, P<0.001) and postoperative mean pulmonary artery
      pressure (R2=0.75, P<0.001). All 4 postoperative deaths occurred in patients with
      a preoperative Rup <60%. CONCLUSIONS: Pulmonary arterial occlusion pressure
      waveform analysis may identify CTEPH patients at risk for persistent pulmonary
      hypertension and poor outcome after PTE. Patients with CTEPH and Rup value <60%
      appear to be at highest risk.

PMID- 14699010
TI  - Isoprenylcysteine carboxyl methyltransferase modulates endothelial monolayer
      permeability: involvement of RhoA carboxyl methylation.
AB  - RhoA and Rac1 regulate formation of stress fibers and intercellular junctions,
      thus modulating endothelial monolayer permeability. Posttranslational
      modifications of RhoA and Rac1 regulate enzyme activity and subcellular
      localization, resulting in altered cellular function. The role of RhoA and Rac1
      carboxyl methylation in modulating endothelial monolayer permeability is not
      known. In this study, we found that inhibition of isoprenylcysteine-O-carboxyl
      methyltransferase (ICMT) with adenosine plus homocysteine or N-acetyl-S
      geranylgeranyl-l-cysteine decreased RhoA carboxyl methylation, RhoA activity, and
      endothelial monolayer permeability, suggesting that RhoA carboxyl methylation may
      play a role in the ICMT-modulated monolayer permeability. Similar studies showed
      no effect of ICMT inhibition on Rac1 carboxyl methylation or localization. Bovine
      pulmonary artery endothelial cells (PAECs) stably overexpressing ICMT-GFP cDNA
      were established to determine if increased ICMT expression could alter RhoA or
      Rac1 carboxyl methylation, activation, and endothelial monolayer permeability.
      PAECs stably overexpressing ICMT demonstrated increased RhoA carboxyl
      methylation, membrane-bound RhoA, and RhoA activity. Additionally, PAECs stably
      overexpressing ICMT had diminished VE-cadherin and beta-catenin at intercellular
      junctions, with resultant intercellular gap formation, as well as enhanced
      monolayer permeability. These effects were blunted by adenosine plus homocysteine
      and by inhibition of RhoA, but not by inhibition of Rac1. These results indicate
      that ICMT modulates endothelial monolayer permeability by altering RhoA carboxyl
      methylation and activation, thus changing the organization of intercellular
      junctions. Therefore, carboxyl methylation of RhoA may modulate endothelial
      barrier function.

PMID- 14699011
TI  - Regulation of connexin43 protein complexes by intracellular acidification.
AB  - Ischemia-induced acidification of astrocytes or cardiac myocytes reduces
      intercellular communication by closing gap junction channels and subsequently
      internalizing gap junction proteins. To determine whether such coupling changes
      might be attributable to altered interactions between connexin43 (Cx43) and other
      proteins, we applied the nigericin/high K+ method to vary intracellular pH (pHi)
      in cultured cortical astrocytes. Intracellular acidification was accompanied by
      internalization of Cx43 with retention of Cx43 scaffolding protein Zonula
      Occludens-1 (ZO-1) at cell surfaces, suggesting that ZO-1 and Cx43 dissociate at
      low pHi. Coimmunoprecipitation studies revealed decreased binding of ZO-1 and
      increased binding of c-Src to Cx43 at low pHi. Resonant mirror spectroscopy was
      used to quantify binding of the SH3 domain of c-Src and the PDZ domains of ZO-1
      to the carboxyl terminal domain of Cx43 (Cx43CT). Data indicate that the c
      Src/Cx43CT interaction is highly pH dependent whereas the ZO-1/Cx43CT interaction
      is not. Moreover, binding of c-Src to Cx43CT prevented and reversed ZO-1/Cx43CT
      binding. We hypothesize that increased affinity of c-Src for Cx43 at low pHi aids
      in separation of Cx43 from ZO-1 and that this may facilitate internalization of
      Cx43. These data suggest that protracted acidification may remodel protein
      protein interactions involving Cx43 and thus provide an important protective
      mechanism to limit lesion spread after ischemic injury.

PMID- 14699012
TI  - NADH oxidase activity of rat cardiac sarcoplasmic reticulum regulates calcium
      induced calcium release.
AB  - NADH and Ca2+ have important regulatory functions in cardiomyocytes related to
      excitation-contraction coupling and ATP production. To elucidate elements of
      these functions, we examined the effect of NADH on sarcoplasmic reticulum (SR)
      Ca2+ release and the mechanisms of this regulation. Physiological concentrations
      of cytosolic NADH inhibited ryanodine receptor type 2 (RyR2)-mediated Ca2+
      induced Ca2+ release (CICR) from SR membranes (IC50=120 micromol/L) and
      significantly lowered single channel open probability. In permeabilized single
      ventricular cardiomyocytes, NADH significantly inhibited the amplitude and
      frequency of spontaneous Ca2+ release. Blockers of electron transport prevented
      the inhibitory effect of NADH on CICR in isolated membranes and permeabilized
      cells, as well as on the activity of RyR2 channels reconstituted in lipid
      bilayer. An endogenous NADH oxidase activity from rat heart copurified with SR
      enriched with RyR2. A significant contribution by mitochondria was excluded as
      NADH oxidation by SR exhibited >9-fold higher catalytic activity (8.8 micromol/mg
      protein per minute) in the absence of exogenous mitochondrial complex I
      (ubiquinone) or complex III (cytochrome c) electron acceptors, but was inhibited
      by rotenone and pyridaben (IC50=2 to 3 nmol/L), antimycin A (IC50=13 nmol/L), and
      diphenyleneiodonium (IC50=28 micromol/L). Cardiac junctional SR treated with
      [3H](trifluoromethyl)diazirinyl-pyridaben specifically labeled a single 23-kDa
      PSST-like protein. These data indicate that NADH oxidation is tightly linked to,
      and essential for, negative regulation of the RyR2 complex and is a likely
      component of an important physiological negative-feedback mechanism coupling SR
      Ca2+ fluxes and mitochondrial energy production.

PMID- 14699013
TI  - Alpha4beta1 integrin mediates selective endothelial cell responses to
      thrombospondins 1 and 2 in vitro and modulates angiogenesis in vivo.
AB  - We examined the function of alpha4beta1 integrin in angiogenesis and in mediating
      endothelial cell responses to the angiogenesis modulators, thrombospondin-1 and
      thrombospondin-2. Alpha4beta1 supports adhesion of venous endothelial cells but
      not of microvascular endothelial cells on immobilized thrombospondin-1, vascular
      cell adhesion molecule-1, or recombinant N-terminal regions of thrombospondin-1
      and thrombospondin-2. Chemotactic activities of this region of thrombospondin-1
      and thrombospondin-2 are also mediated by alpha4beta1, whereas antagonism of
      fibroblast growth factor-2-stimulated chemotaxis is not mediated by this region.
      Immobilized N-terminal regions of thrombospondin-1 and thrombospondin-2 promote
      endothelial cell survival and proliferation in an alpha4beta1-dependent manner.
      Soluble alpha4beta1 antagonists inhibit angiogenesis in the chick chorioallantoic
      membrane and neovascularization of mouse muscle explants. The latter inhibition
      is thrombospondin-1-dependent and not observed in explants from thrombospondin-1
      /- mice. Antagonizing alpha4beta1 may in part block proangiogenic activities of
      thrombospondin-1 and thrombospondin-2, because N-terminal regions of
      thrombospondin-1 and thrombospondin-2 containing the alpha4beta1 binding sequence
      stimulate angiogenesis in vivo. Therefore, alpha4beta1 is an important
      endothelial cell receptor for mediating motility and proliferative responses to
      thrombospondins and for modulation of angiogenesis.

PMID- 14699014
TI  - Homocysteine induces endothelial cell detachment and vessel wall thickening
      during chick embryonic development.
AB  - Homocysteine affects the migration and differentiation of neural crest cells in
      vitro and can result in neural tube defects in vivo. Furthermore, homocysteine
      has been described as an important determinant in vascular disease in human
      adults. However, little is known about the effects of homocysteine on the
      development of embryonic vessels. In this study, we injected homocysteine (30
      micromol/L) into the neural tube lumen of chick embryos at the time point of
      neural crest cell emigration, and analyzed the effects on the neural crest
      derived pharyngeal arch arteries, like the brachiocephalic arteries, and the
      mesoderm-derived arteries, such as the dorsal aorta. By stage HH35, we observed
      detachment of the endothelium, decreased expression of the extracellular matrix
      proteins fibrillin-2, and fibronectin in the pharyngeal arch arteries, whereas
      the dorsal aorta was identical in homocysteine-neural tube-injected and control
      embryos. No effect of homocysteine on endothelin-1 mRNA expression was observed.
      By stage HH40, the brachiocephalic arteries of homocysteine-neural tube-injected
      embryos displayed a decreased lumen diameter, an increased intima- and media
      thickness, and an increased number of actin layers compared with the
      brachiocephalic arteries in control embryos. We propose that homocysteine affects
      the neural crest-derived smooth muscle cells and their extracellular matrix
      proteins in the pharyngeal arch arteries, resulting in an abnormal smooth muscle
      to endothelial cell interaction, leading to endothelial cell detachment. We
      suggest that, as in adult life, increased homocysteine concentrations lead to
      vascular damage in the embryo. This prenatal damage might increase the
      susceptibility to develop vessel pathology later in life.

PMID- 14699015
TI  - Interleukin-6 induces oxidative stress and endothelial dysfunction by
      overexpression of the angiotensin II type 1 receptor.
AB  - Angiotensin II type 1 (AT1) receptor activation as well as proinflammatory
      cytokines such as interleukin-6 (IL-6) are involved in the development and
      progression of atherosclerosis. The detailed underlying mechanisms including
      interactions between inflammatory agonists and the renin-angiotensin system are
      poorly understood. Stimulation of cultured rat aortic vascular smooth muscle
      cells (VSMCs) with IL-6 led to upregulation of AT1 receptor mRNA and protein
      expression, as assessed by Northern and Western blot experiments. Nuclear run-on
      and transcription blockade experiments showed that IL-6 increases AT1 receptor
      mRNA de novo synthesis but not mRNA stability. Preincubation of VSMCs with IL-6
      resulted in an enhanced angiotensin II-induced production of reactive oxygen
      species, as assessed by DCF fluorescence laser microscopy. Treatment of C57BL/6J
      mice with IL-6 for 18 days increased vascular AT1 receptor expression (real-time
      RT-PCR) and angiotensin II-induced vasoconstriction, enhanced vascular superoxide
      production (L-012 chemiluminescence, DHE fluorescence), and impaired endothelium
      dependent vasodilatation. These effects were completely omitted in AT1 receptor
      knockout mice (AT1A-/- mice). Upregulation of vascular AT1 receptor expression in
      vitro and in vivo is decisively involved in IL-6-induced propagation of oxidative
      stress and endothelial dysfunction. This interaction of the proinflammatory
      cytokine IL-6 with the renin-angiotensin system may represent an important
      pathogenetic mechanism in the atherosclerotic process.

PMID- 14699016
TI  - Adenoviral transfer of endothelial nitric oxide synthase attenuates lesion
      formation in a novel murine model of postangioplasty restenosis.
AB  - OBJECTIVE: Restenosis remains a major late complication of percutaneous
      transluminal coronary angioplasty (PTCA), for which the development of prevention
      strategies has thus far been hampered by the lack of a representative and
      practical animal model. We have, therefore, developed a murine model of PTCA
      induced restenosis. METHODS AND RESULTS: Rigid probe angioplasty of pre-existing
      atherosclerotic lesions in the carotid arteries of ApoE-deficient mice was found
      to result in an increase in lesion size (0.14+/-0.04x10(5) microm2 to 0.42+/
      0.09x10(5) microm2, P=0.007) with a smooth muscle cell-rich, fibrotic lesion
      morphology. In an additional experiment, lesions were incubated immediately after
      angioplasty with adenovirus bearing an endothelial nitric oxide synthase (eNOS)
      transgene (Ad.APT.eNOS), or an "empty" control virus (Ad.APT.empty) at a titer of
      1.5x10(9) pfu/mL. Ad.APT.eNOS treatment was seen to lead to a 73.1% reduction in
      plaque size (0.27+/-0.04x10(5) microm2 versus 1.02+/-0.39x10(5) microm2, P=0.07),
      which translated to a significantly lowered average degree of stenosis (33.6+/
      4.1% versus 74.6+/-14.0%, P=0.02). Ad.APT.eNOS also decreased lesional collagen
      content from 29.1% to 4.8% (P<0.001). CONCLUSIONS: We believe that we have
      established a representative murine model of postangioplasty restenosis, which
      may serve to elucidate the mechanisms underlying restenosis and to evaluate
      potential antirestenotic therapies.

PMID- 14699017
TI  - Characterization of two types of endothelial progenitor cells and their different
      contributions to neovasculogenesis.
AB  - OBJECTIVE: Endothelial progenitor cells (EPC) in one study group is not the same
      as EPC in other investigators, suggesting that EPC is not a single type of cell
      population. In this study, we tried to demonstrate the heterogeneity of EPC.
      METHODS AND RESULTS: We cultured total mononuclear cells from human peripheral
      blood to get two types of EPC sequentially from the same donors. We called them
      early EPC and late EPC. Early EPC with spindle shape showed peak growth at 2 to 3
      weeks and died at 4 weeks, whereas late EPC with cobblestone shape appeared late
      at 2 to 3 weeks, showed exponential growth at 4 to 8 weeks, and lived up to 12
      weeks. Late EPC was different from early EPC in the expression of VE-cadherin,
      Flt-1, KDR, and CD45. Late EPC produced more nitric oxide, incorporated more
      readily into human umbilical vein endothelial cells monolayer, and formed
      capillary tube better than early EPC. Early EPC secreted angiogenic cytokines
      (vascular endothelial growth factor, interleukin 8) more so than late EPC during
      culture in vitro. Both types of EPC showed comparable in vivo vasculogenic
      capacity. CONCLUSIONS: We found two types of EPC from a source of adult
      peripheral blood that might have different roles in neovasculogenesis based on
      the identified differences.

PMID- 14699018
TI  - Upregulation of SR-PSOX/CXCL16 and recruitment of CD8+ T cells in cardiac valves
      during inflammatory valvular heart disease.
AB  - OBJECTIVE: SR-PSOX/CXCL16 is a transmembrane chemokine and is implicated in
      activated CD8+ T cell trafficking. In the present study, we examined the
      expression pattern of SR-PSOX/CXCL16 in the heart and investigated a potential
      role of SR-PSOX/CXCL16 in inflammatory valvular heart disease. METHODS AND
      RESULTS: Initial expression of SR-PSOX/CXCL16 in murine embryos was detected in
      endothelial cells lining endocardial cushions in the forming heart at E11.5. From
      mid-gestation to adult, expression of this gene in the heart was exclusively
      observed in valvular endothelial cells. Examination of SR-PSOX/CXCL16 expression
      in human cardiac valves demonstrated that SR-PSOX/CXCL16 was strongly expressed
      in valvular and neocapillary endothelial cells in patients with infective
      endocarditis. SR-PSOX/CXCL16 expression in neocapillary endothelial cells was
      also observed in patients with rheumatic and atherosclerotic valvular disease.
      Moreover, CD8+ T cells were distributed closely to endothelial cells expressing
      SR-PSOX/CXCL16. In vitro adhesion assays showed that SR-PSOX/CXCL16 induced
      adhesion of activated CD8+ T cells to vascular cell adhesion molecule-1 (VCAM-1)
      through very late antigen-4 (VLA-4) activation. Furthermore, SR-PSOX/CXCL16
      stimulated interferon-gamma (IFN-gamma) production by CD8+ T cells. CONCLUSIONS:
      SR-PSOX/CXCL16 may be involved in CD8+ T cell recruitment through VLA-4
      activation and stimulation of IFN-gamma production by CD8+ T cells during
      inflammatory valvular heart disease.

PMID- 14699019
TI  - Transforming growth factor beta and atherosclerosis: so far, so good for the
      protective cytokine hypothesis.
AB  - The role of the anti-inflammatory cytokine transforming growth factor beta (TGF
      beta) in atherosclerosis has been the subject of considerable debate for a
      decade. In the early 1990s, we postulated that TGF-beta played an important role
      in maintaining normal vessel wall structure and that loss of this protective
      effect contributed to the development of atherosclerosis. We termed this the
      protective cytokine hypothesis. This proposal was slow to gain broad acceptance,
      however, because at that time there were little data available on the role of TGF
      beta during the development of atherosclerosis but much information about its
      role during trauma-induced neointima formation. Because TGF-beta apparently
      aggravates neointima formation, both by inhibiting endothelial regeneration and
      by promoting fibrosis, it was difficult to accept that its presence might
      ameliorate the superficially similar atherogenesis process. But several recent
      studies revealed beyond doubt the fact that TGF-beta protects against lipid
      lesion formation, at least in mouse models of atherosclerosis. Therefore, two
      important questions remain. First, is the role of TGF-beta in vascular biology
      similar in humans and in mice? Secondly, how important, compared with defects in
      thrombosis or lipoprotein metabolism, is the protective role of TGF-beta during
      atherogenesis?

PMID- 14699020
TI  - Betaine as a determinant of postmethionine load total plasma homocysteine before
      and after B-vitamin supplementation.
AB  - OBJECTIVE: Betaine is a substrate in the betaine-homocysteine methyltransferase
      reaction, converting homocysteine to methionine. There are only sparse data on
      plasma betaine as a determinant of the plasma total homocysteine (tHcy)
      concentration. METHODS AND RESULTS: Ninety patients undergoing coronary
      angiography were randomized into 4 groups administered oral: (1) folic acid (0.8
      mg), vitamin B12 (0.4 mg), and vitamin B6 (40 mg); (2) folic acid and vitamin
      B12; (3) vitamin B6 alone; or (4) placebo. Nonfasting blood samples were
      collected at baseline and 3, 14, and 28 days and 3, 6, and 12 months after
      treatment start. A 4-hour methionine-loading test (0.1 g/kg) was performed at
      baseline and after 3 months. At baseline, median (interquartile range) plasma
      betaine was 36.9 micromol/L (range: 30.3 to 46.8) and was increased by 15% after
      methionine loading. The postmethionine load (PML) increase in tHcy was inversely
      related to plasma betaine (beta=-0.29, P=0.02) and even more strongly to PML
      betaine (beta=-0.47, P<0.001). After 3 months of intervention, the relation
      between the PML increase in tHcy and PML betaine was weakened (beta=-0.33,
      P=0.007). CONCLUSIONS: Plasma betaine is a strong determinant of the PML increase
      in tHcy in subjects not supplemented with B-vitamins.

PMID- 14699023
TI  - Detection and treatment of the micrometastases of gastric cancer.

PMID- 14699021
TI  - Effect of lower dosage of oral conjugated equine estrogen on inflammatory markers
      and endothelial function in healthy postmenopausal women.
AB  - OBJECTIVE: Although oral estrogen replacement therapy (ERT) in postmenopausal
      women improves endothelial function, it also increases plasma C-reactive protein
      (CRP) and interleukin-6 (IL-6) concentration. The proinflammatory effect of oral
      ERT may explain the increased risk of coronary heart disease (CHD) associated
      with this treatment. Recent observational studies have demonstrated that a lower
      dose of oral estrogen reduces the risk for CHD. The purpose of the present study
      was to investigate the effects of low-dose oral estrogen on vascular inflammatory
      markers and endothelium-dependent vasodilation in postmenopausal women. METHODS
      AND RESULTS: Postmenopausal women were randomized into 3 groups to receive no
      treatment (n=14) or oral conjugated equine estrogen (CEE) at a dosage of 0.625 mg
      (n=15) or 0.3125 mg (n=15) daily for 3 months. CEE at a dosage of 0.625 mg
      resulted in significant increases in plasma concentrations of CRP from 690.9+/
      749.5 to 1541.9+/-1608.0 ng/mL, serum amyloid A from 6.12+/-4.15 to 8.25+/-4.40
      microg/mL, and IL-6 from 1.45+/-0.73 to 2.35+/-1.16 pg/mL. In contrast, CEE at a
      dosage of 0.3125 mg had no effect on these inflammatory markers. Both dosages of
      estrogen significantly decreased E-selectin concentration, whereas the
      concentrations of intercellular and vascular cell adhesion molecules remained
      unchanged. In both CEE groups, flow-mediated vasodilation in the brachial artery
      was increased significantly, whereas nitroglycerine-induced vasodilation was
      unaltered. CONCLUSIONS: Oral CEE at a low dose of 0.3125 mg in postmenopausal
      women eliminated the adverse effects of high-dosage oral CEE on vascular
      inflammatory markers in addition to preserving the favorable effects of estrogen
      on cell adhesion molecules and endothelial function.

PMID- 14699024
TI  - Primary vaginal melanoma: a rare and problematic clinical entity.

PMID- 14699025
TI  - In search of better outcome predictors for patients following resection of
      colorectal metastases.

PMID- 14699026
TI  - Hormone replacement therapy: a promoter and modulator of breast cancer.

PMID- 14699027
TI  - Locoregional control of breast cancer: surgical technique does matter.

PMID- 14699028
TI  - Application of molecular diagnosis for detection of peritoneal micrometastasis
      and evaluation of preoperative chemotherapy in advanced gastric carcinoma.
AB  - BACKGROUND: In advanced gastric cancer, peritoneal recurrence is the main cause
      of death after curative surgical resection. The aim of this report was to
      describe a novel approach for quantitative genetic diagnosis using peritoneal
      lavage for the identification of patients at high risk for peritoneal recurrence
      and for evaluation of the clinical response to intraperitoneal chemotherapy in
      advanced gastric cancer. METHODS: Nineteen patients with advanced gastric cancer
      who underwent staging laparoscopy and intraperitoneal chemotherapy before
      surgical resection or systemic chemotherapy between June 1999 and September 2001
      were enrolled in this study. All peritoneal lavage specimens, collected at both
      staging laparoscopy and gastrectomy, were subjected to real-time quantitative
      genetic diagnosis. RESULTS: The reverse transcriptase polymerase chain reaction
      (RT-PCR) values decreased in 8 cases, stabilized as negative in 5, and increased
      in 6 during therapy. Patients whose RT-PCR values diminished and were ultimately
      negative survived except for one, and all but one patient whose values increased
      during treatment died of recurrence. CONCLUSIONS: Quantitative evaluation of
      genetic changes can provide accurate, useful information on the effects of
      preoperative intra-abdominal chemotherapy and overall prognosis for patients with
      advanced gastric cancer.

PMID- 14699029
TI  - Lymphazurin 1% versus 99mTc sulfur colloid for lymphatic mapping in colorectal
      tumors: a comparative analysis.
AB  - BACKGROUND: The combination of isosulfan blue (Lymphazurin) 1% and 99(m)Tc sulfur
      colloid (TSC) may improve the feasibility and accuracy of lymphatic mapping for
      colorectal cancer. METHODS: At laparotomy, 1 to 2 mL of isosulfan blue and 1 mCi
      of TSC were injected subserosally. Sentinel lymph node (SLN) designation was
      based on blue staining for isosulfan blue and increased radioactivity for TSC.
      Focused pathologic analysis of the SLNs and standard pathologic examination of
      the remaining specimen were performed. RESULTS: A total of 57 consecutive
      patients were studied (median age, 71 years; 27 men and 30 women). Mapping was
      successful in 100% of patients with isosulfan blue and in 89% with TSC (P =.47).
      Lymphatic mapping was accurate in 93% of patients with isosulfan blue versus 92%
      with TSC (P =.53). The combined accuracy was 95%. A total of 709 lymph nodes were
      found (12.4 per patient): 553 non-SLNs (5.6% nodal positivity) versus 156 SLNs
      (16.7% nodal positivity; P <.0001). Isosulfan blue detected 152 SLNs, TSC
      detected 100, and both modalities detected 96. Of the SLNs detected by isosulfan
      blue only, 10.7% had nodal metastases, whereas 19.8% of SLNs detected with both
      modalities had nodal metastases (P =.028). Nodal disease was detected in 41% of
      patients with invasive carcinoma. Metastases were detected only in the SLNs in
      26% and only by micrometastases in 11% of these patients. CONCLUSIONS: These data
      confirm the efficacy of isosulfan blue and TSC for SLN mapping in colorectal
      tumors. No significant difference with respect to feasibility or accuracy exists
      between isosulfan blue and TSC. The metastatic yield is significantly higher in
      SLNs identified by both modalities compared with isosulfan blue only.

PMID- 14699030
TI  - Composite pelvic exenteration: is it worthwhile?
AB  - BACKGROUND: In locally advanced pelvic cancer, tumor fixation to the bony pelvis
      is regarded as unresectable and often inoperable. Few data exist regarding the
      futility or utility of pelvic exenteration with en bloc resection of involved
      portions of the bony pelvis. METHODS: Thirty-four of 625 patients undergoing
      radical pelvic procedures had an en bloc resection of pelvic organs with portions
      of the bony pelvis. There were 19 female and 15 male patients, and the median age
      was 59 years. Primary neoplasms included 19 rectal, 6 cervicouterine, 4 anal, 3
      vaginal, 1 sarcoma, and 1 penile. All but three patients underwent preoperative
      pelvic irradiation. Pelvic exenterations were posterior in 7 patients, anterior
      in 3, supralevator in 3, and total in 21 patients. Pelvic bony resections
      included portions of the sacrum-coccyx in 18 patients, ischium in 5, pubic
      symphysis in 4, and ischial pubic rami in 4, and hemipelvectomy was performed in
      3. RESULTS: Surgical morbidity occurred in 67.6% (23) of 24 patients. Median
      follow-up was 37 months. Pelvic or perineal tumor recurrence was concurrent with
      distant metastases in 9 patients (26.4%); 6 (17.6%) had only distant relapse, and
      2 (5.8%) died with local recurrence alone. Overall cancer-related mortality rate
      was 50%. Five-year overall and cancer-specific survival rates were 44% and 52%,
      respectively. CONCLUSIONS: Substantial survival can be accomplished for patients
      whose tumors are fixed to limited portions of the bony pelvis. These procedures
      are still associated with substantial morbidity, but operative mortality is
      infrequent.

PMID- 14699031
TI  - Primary vaginal melanoma: a critical analysis of therapy.
AB  - BACKGROUND: Primary vaginal melanoma is a rare and highly malignant disease. The
      impact of therapy on outcomes is poorly understood. METHODS: Records of all
      patients treated for primary vaginal melanoma at Memorial Sloan-Kettering Cancer
      Center from 1977 to 2001 were reviewed. Survival analysis was performed based on
      appropriate patient, tumor, and treatment variables. Pathologic materials were
      reviewed to confirm the original diagnosis and examine appropriate
      clinicopathologic features. RESULTS: Thirty-five women were treated for vaginal
      melanoma; the primary treatment selected was surgical for 69% (24) and
      radiotherapy for 31% (11) of the patients. Surgical removal of the tumor was
      achieved in 92% (22) of the 24 patients selected for surgical therapy. At
      operation, radical excision with en bloc removal of involved pelvic organs was
      performed in 50% (12) of the 24 patients, a wide excision was performed in 42%
      (10), and a total vaginectomy was performed in 8% (2). Elective pelvic lymph node
      dissection was performed in 74% (26) of the 35 cases. Lymph node metastasis was
      found in only 8% (2) of these 26 patients. The overall median survival was 20
      months. Primary surgical therapy was associated with longer overall survival (25
      vs. 13 months; P =.039). Recurrence-free survival was not associated with the
      extent of surgery. None of the examined clinicopathologic features were
      associated with survival differences. CONCLUSIONS: The prognosis is poor for
      patients with primary vaginal melanoma. Improved clinical outcomes were
      associated with surgical removal of gross disease whenever possible. Because of
      the low rate of lymph node metastasis, elective pelvic lymph node dissection is
      not obligatory. In cases of surgically unresectable disease, primary radiation
      therapy is indicated.

PMID- 14699032
TI  - Correlation between MUC5AC expression and the prognosis of patients with
      adenocarcinoma of the uterine cervix.
AB  - BACKGROUND: Mucin expression shows some correlation with prognosis in patients
      with various cancers. However, few studies have been conducted on adenocarcinomas
      of the uterine cervix. METHODS: An immunohistochemical study with a monoclonal
      anti-MUC5AC antibody, 45M1, was performed on 47 adenocarcinomas of the uterine
      cervix and on 40 specimens of normal endocervical epithelium. The correlations
      between clinicopathologic variables and MUC5AC expression were evaluated in the
      cervical adenocarcinomas. RESULTS: A significant reduction of MUC5AC expression
      was evident in the adenocarcinomas of the cervix in comparison with that in the
      normal endocervical epithelium (53.2% vs. 100%; P <.001). MUC5AC expression was
      correlated with paracervical invasion and histological type. Patients with
      negative MUC5AC expression showed poorer survival than those with positive MUC5AC
      expression (P =.03). However, multivariate analysis revealed that only the depth
      of invasion was an independent prognostic variable. CONCLUSIONS: MUC5AC
      expression was suppressed in adenocarcinoma of the uterine cervix. Absence of
      MUC5AC expression seems correlated with worse survival.

PMID- 14699033
TI  - Human telomerase reverse transcriptase (hTERT) and Ki-67 are better predictors of
      survival than established clinical indicators in patients undergoing curative
      hepatic resection for colorectal metastases.
AB  - BACKGROUND: We evaluated hTERT and Ki-67 expression in patients who underwent
      curative resection of hepatic colorectal metastases to determine if these markers
      of cell proliferation correlated better with survival than an established scoring
      system that is based on clinical predictors. METHODS: Patients operated on
      between 1993 and 1997 whose survival time was known were analyzed. For each
      patient, the clinical prognostic score was derived on the basis of primary node
      status, disease-free interval, number of hepatic tumors, largest tumor, and
      carcinoembryonic antigen level, and tumor specimens were analyzed for Ki-67 and
      hTERT with use of standard immunohistochemical techniques. The
      immunohistochemical analysis was blinded to all patient characteristics. RESULTS:
      The study included 66 patients. Twenty-six survived less than 2 years after
      surgery, 19 survived 2-5 years, and 21 survived more than 5 years. Ki-67
      positivity and hTERT positivity (labeling indexes greater than or equal to 50%)
      were observed in 24 patients and 23 patients, respectively. The clinical score
      did not predict survival, although there was a weak trend toward a lower score in
      patients with better survival. Both Ki-67 (P =.04) and hTERT (P =.0001)
      correlated better with survival than did the clinical score. CONCLUSIONS: In
      patients undergoing curative resection of hepatic colorectal metastases, hTERT
      and Ki-67 are better predictors of survival than is a score based on clinical
      features.

PMID- 14699034
TI  - The characteristics of malignant breast tumors in hormone replacement therapy
      users versus nonusers.
AB  - BACKGROUND: The purpose of this study was to investigate the characteristics of
      breast cancer in hormone replacement therapy (HRT) users vs. nonusers. METHODS:
      We investigated the characteristics of all patients between the ages of 50 and 75
      years with breast tumors. Then, an age-adjusted group of 55 nonusers was chosen
      to match and compare with HRT users. RESULTS: Of the 243 patients available for
      evaluation, 55 (22.6%) used HRT. Disease stages in HRT users vs. nonusers were as
      follows: ductal carcinoma in situ (DCIS), 20% and 17.1%; stage I, 45.5% and
      41.7%; stage II, 30.9% and 26.2%; stage III, 3.6% and 13.4%; and stage IV, 0% and
      1.6% (P =.27). In the age-adjusted cohort, stages in nonusers were as follows:
      DCIS, 7.3%; stage I, 47.3%; stage II, 25.5%; stage III, 20%; and stage IV, 0% (P
      =.03). Tumor grades in HRT users vs. nonusers were as follows: grade I, 30.4% and
      15.7%; grade II, 52.2% and 52.2%; and grade III, 17.4% and 32.1% (P =.035).
      Grades in cohort nonusers were as follows: I, 13.2%; II, 52.8%; and III, 34% (P
      =.05). In the invasive tumors, the positive estrogen receptor (ER) rates were
      81.6% and 85.7% (P =.89); positive progesterone receptor (PR) rates were 53.1%
      and 54% (P =.95); and Her 2-neu positive rates were 18.4% and 17.6% (P =.95),
      respectively. No significant difference was found in intratumor DCIS, vascular
      invasion, and Ki-67 (P =.14,.9, and.79, respectively). The rate of lobular and
      favorable histological types was higher in the HRT user group: 26.6% vs. 15%.
      CONCLUSIONS: Breast tumors in HRT users vs. nonusers were of a significantly
      lower stage and grade and accounted for a higher number of favorable histological
      types, but all other parameters were similar in the two groups.

PMID- 14699035
TI  - Breast cancer in patients with residual invasive carcinoma is more accurately
      staged with additive tumor size assessment.
AB  - BACKGROUND: Accurate assessment of tumor size for patients with breast cancer
      undergoing re-excision following breast-conserving therapy is important for
      appropriate staging and adjuvant treatment. We investigated the accuracy of
      additive vs. nonadditive size assessment in determining final tumor stage.
      METHODS: Patients with infiltrating carcinoma in the initial excision and in at
      least one additional re-excision (re-excision positive; n = 89) had tumor size
      assessed with additive and nonadditive techniques. This group was compared with
      patients undergoing re-excision but without identifiable residual carcinoma (re
      excision negative; n = 105) regarding rates of lymph node (LN) metastasis.
      RESULTS: The re-excision positive patients had a different median final tumor
      size depending on the size assessment technique used (nonadditive: 1.8 cm;
      additive: 3.0 cm; P <.0001). Both groups of patients had a median tumor size
      consistent with T1c staging in nonadditive size assessment. However, re-excision
      positive patients had a significantly higher incidence of LN metastasis (P <.05)
      than did re-excision negative patients. Both groups were then separated into T1
      and T2 stages and the LN metastasis rates were assessed. Compared with
      nonadditive size assessment, additive size assessment distributed re-excision
      positive patients into T stages whereby the LN metastasis rates more closely
      approximated those of re-excision negative patients (T1, 3% vs. 6% difference;
      T2, 4% vs. 13% difference). CONCLUSIONS: With regard to LN metastasis, staging
      for patients with residual invasive carcinoma in re-excision specimens is more
      accurate with additive tumor size assessment.

PMID- 14699036
TI  - Autofluorescence and diffuse reflectance properties of malignant and benign
      breast tissues.
AB  - BACKGROUND: Fluorescence spectroscopy is an evolving technology that can rapidly
      differentiate between benign and malignant tissues. These differences are thought
      to be due to endogenous fluorophores, including nicotinamide adenine
      dinucleotide, flavin adenine dinucleotide, and tryptophan, and absorbers such as
      beta-carotene and hemoglobin. We hypothesized that a statistically significant
      difference would be demonstrated between benign and malignant breast tissues on
      the basis of their unique fluorescence and reflectance properties. METHODS:
      Optical measurements were performed on 56 samples of tumor or benign breast
      tissue. Autofluorescence spectra were measured at excitation wavelengths ranging
      from 300 to 460 nm, and diffuse reflectance was measured between 300 and 600 nm.
      Principal component analysis to dimensionally reduce the spectral data and a
      Wilcoxon ranked sum test were used to determine which wavelengths showed
      statistically significant differences. A support vector machine algorithm
      compared classification results with the histological diagnosis (gold standard).
      RESULTS: Several excitation wavelengths and diffuse reflectance spectra showed
      significant differences between tumor and benign tissues. By using the support
      vector machine algorithm to incorporate relevant spectral differences, a
      sensitivity of 70.0% and specificity of 91.7% were achieved. CONCLUSIONS: A
      statistically significant difference was demonstrated in the diffuse reflectance
      and fluorescence emission spectra of benign and malignant breast tissue. These
      differences could be exploited in the development of adjuncts to diagnostic and
      surgical procedures.

PMID- 14699037
TI  - Effect of papillary and chromophobe cell type on disease-free survival after
      nephrectomy for renal cell carcinoma.
AB  - BACKGROUND: The clinical staging of renal cortical tumors traditionally has not
      evaluated the potential effect of histological subtypes on survival. Evidence
      suggests that conventional clear cell renal cell carcinoma (RCC) and
      nonconventional clear cell RCC (chromophobe and papillary) have different
      metastatic potential. Using a large renal tumor database, we examined the effect
      of tumor histology on the pattern of metastasis and patient survival. METHODS:
      All patients with nonmetastatic renal cortical tumors undergoing partial or
      radical nephrectomy were identified from a renal tumor database between July 1989
      and July 2002. Kaplan-Meier and Cox regression tests were used for statistical
      analysis. RESULTS: Analysis revealed 1057 patients: 794 with conventional clear
      cell RCC, 157 with papillary RCC, and 106 with chromophobe RCC. Metastasis
      occurred in 95 conventional clear cell RCC, 9 papillary RCC, and 6 chromophobe
      RCC with a median follow-up of 34.6, 43.0, and 33.2 months, respectively. Using
      log-rank analysis, chromophobe and papillary RCC were associated with an improved
      disease-free survival at 5 years (P =.009 and.015, respectively). Multivariate
      analysis revealed tumor size, stage, and chromophobe histology as significant
      variables for disease progression. CONCLUSIONS: Renal cortical tumors have
      distinct histological subtypes with varying degrees of metastatic potential.
      Conventional clear cell RCC, which comprises two thirds of renal cortical tumors
      presenting with localized disease, has a less favorable outcome when compared
      with papillary and chromophobe RCC. Controlling for size and stage, chromophobe,
      and not papillary, RCC was a significant variable for disease progression
      compared with conventional clear cell RCC. Knowledge of renal cortical tumor
      histological subtype is critical for projecting prognosis, tailoring follow-up
      strategies, and designing clinical trials.

PMID- 14699038
TI  - Atypical lipomatous tumor/well-differentiated liposarcoma of the extremity and
      trunk wall: importance of histological subtype with treatment recommendations.
AB  - BACKGROUND: This study defines the behavior and classification of atypical
      lipomatous tumors (ALT) and well-differentiated liposarcomas (WDLS) of the
      extremity and trunk. METHODS: A total of 91 well-differentiated lipomatous tumors
      of the extremity and trunk were identified from a soft tissue tumor database
      between July 1982 and June 2001. A soft tissue pathologist, blinded to prior
      diagnosis and clinical outcome, reviewed histology. Those composed predominantly
      of mature adipose tissue with scattered atypical stromal cells and scant
      lipoblasts or fibrosis were ALTs. Tumors with lipoblasts but <25% fibrosis were
      termed lipoma-like WDLS, and those with >/=25% fibrosis were identified as
      sclerosing WDLS. Clinical factors were analyzed to assess effects on local
      recurrence-free survival (LRFS). RESULTS: Histological review identified 34 ALTs
      and 57 WDLSs. Of the WDLSs, 29 were lipoma-like and 28 were sclerosing. Five-year
      and 10-year LRFS were 100% +/- 0% and 78% +/- 9%, respectively. Factors evaluated
      were age, sex, tumor site, tumor size, histology, presentation status, margin
      status, and adjuvant radiotherapy. Positive resection margins and sclerosing
      histology were associated with reduced LRFS. Dedifferentiation was observed in
      three tumors (3%). CONCLUSIONS: Lipoma-like WDLSs and ALTs share similar
      histological features and favorable behavior. Margin-positive sclerosing WDLSs
      have a 10-year LRFS of only 17% and should undergo function-preserving re
      excision when possible, or adjuvant radiotherapy.

PMID- 14699039
TI  - Melanoma-inhibiting activity assay predicts survival in patients receiving a
      therapeutic cancer vaccine after complete resection of American Joint Committee
      on Cancer Stage III Melanoma.
AB  - BACKGROUND: More than half of melanoma patients rendered disease free by lymph
      node dissection will experience disease recurrence. We hypothesized that serum
      levels of melanoma-inhibiting activity (MIA) protein might be useful to stratify
      risk and identify subclinical recurrence in patients undergoing adjuvant
      immunotherapy. We examined MIA levels in the serum of stage III patients treated
      after surgery with a therapeutic cancer vaccine. METHODS: Three cohorts of 25
      patients were randomly selected from our melanoma database on the basis of time
      to death (group 1, <1 year; group 2, 1-5 years; group 3, >5 years.) Prospectively
      collected serum samples were assayed in a blinded fashion for MIA by enzyme
      linked immunosorbent assay. RESULTS: MIA was increased at any time in 19 (76%) of
      25, 4 (16%) of 25, and 1 (4%) of 25 patients in groups 1, 2, and 3, respectively.
      The median survival was 11 months for the 25 patients with increased MIA and >75
      months for the 50 patients with normal MIA. MIA increased above normal a median
      of 1 month (mean, 75 days) before clinical recurrence. All patients with
      increased MIA after 2 months of treatment subsequently died of melanoma. One
      patient in whom initially increased levels decreased to normal within 2 months is
      disease free. CONCLUSIONS: Serum MIA levels provide important prognostic
      information early in the course of stage III melanoma and often detect melanoma
      recurrences before clinical evidence of disease.

PMID- 14699040
TI  - The utility of frozen section evaluation for follicular thyroid lesions.
AB  - BACKGROUND: Because fine-needle aspiration cannot reliably discriminate between
      benign and malignant follicular thyroid lesions, some surgeons use intraoperative
      frozen section (FS) to guide operative management. To determine the utility of FS
      for these lesions, we reviewed our institutional experience. METHODS: Between
      1994 and 2001, 152 patients underwent surgical resection for follicular
      neoplasms. RESULTS: The mean age of the patients was 47 years, and 76% were
      female. Forty-one (32%) FSs were reported as benign, 5 (4%) as malignant, and 3
      (2%) as indeterminate, and in 80 (62%), the diagnosis was "follicular lesion,
      deferred to permanent histology." On paraffin section, all patients with
      malignant FSs had thyroid cancer, and all 41 patients with benign FSs had benign
      lesions. Thus, FS for diagnosis of follicular thyroid cancer had a sensitivity,
      specificity, positive predictive value, and accuracy of 67%, 100%, 100%, and 96%,
      respectively. In most cases (64%), FS rendered no additional information at the
      time of operation. Therefore, the cost per useful FS was $7800, which is higher
      than the charge of a completion thyroidectomy (approximately $6000). CONCLUSIONS:
      FS analysis for follicular lesions seems to be highly specific and accurate.
      However, because of the low sensitivity, routine use of FS is not cost-effective
      in patients with follicular thyroid lesions.

PMID- 14699041
TI  - A new in vitro assay for human tumor angiogenesis: three-dimensional human tumor
      angiogenesis assay.
AB  - BACKGROUND: A human tissue-based angiogenesis assay is needed to study the
      biology of angiogenesis in human tumor tissue and to tailor drug selection for
      patients. METHODS: Fragments of tumor tissue are embedded in fibrin gels
      containing medium 199, endothelial growth medium, fetal bovine serum, and epsilon
      aminocaproic acid. Tumor implants sprout angiogenic vessels that progressively
      grow into the fibrin matrix. The differential growth pattern of tumor cells and
      angiogenic vessels in the fibrin gel matrix separates the angiogenic vessels and
      the tumor stroma into independently observable regions (vessel and tumor
      compartments). The reproducibility of the assay was tested by using fresh tissue
      obtained from human tumor xenografts (IMR-32 [neuroblastoma], MDA-MB-231 [breast
      cancer], and LNCaP [prostate cancer]) grown in nude mice and from fresh surgical
      breast and thyroid cancer specimens. RESULTS: All tumor fragments studied showed
      angiogenic sprouting into the fibrin matrix. This created an angiogenic vessel
      compartment, which was separate from the tumor fragment. The capillary nature of
      sprouting was confirmed histologically by factor VIII immunohistochemistry. The
      angiogenic growth fraction was >80% in all groups studied. CONCLUSIONS: This
      assay may allow functional assessment of the angiogenic potential of human tumors
      and simultaneous evaluation of a therapeutic agent's antitumor and antiangiogenic
      effects by virtue of its dual-compartmental structure.

PMID- 14699042
TI  - Protein phosphatase 2A inhibition induces cerebellar long-term depression and
      declustering of synaptic AMPA receptor.
AB  - Phosphorylation of synaptic (RS)-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid) (AMPA) receptors (AMPARs) is an essential component of
      cerebellar long-term depression (LTD), a form of synaptic plasticity involved in
      motor learning. Here, we report that protein phosphatase 2A (PP-2A) plays a
      specific role in controlling synaptic strength and clustering of AMPARs at
      synapses between granule cells and Purkinje cells. In 22- to 35-day cerebellar
      cultures, specific inhibition of postsynaptic PP-2A by fostriecin (100 nM) or
      cytostatin (10-60 microM) induced a gradual and use-dependent decrease of
      synaptic current evoked by the stimulation of a single granule cell, without
      altering receptor kinetics nor passive electrical properties. By contrast, PP-2A
      inhibition had no effect on immature Purkinje cells (12-15 days). Concurrent PP
      2A inhibition and AMPAR stimulation induced a reduction of miniature synaptic
      currents and a reduction of AMPAR density at synapses. Either PP-2A inhibitor
      alone or AMPA stimulation alone had no significant effect. Inhibition of PP-1 by
      inhibitor 1 (10-27 units/microl) had no effect on synaptic current. Synaptic
      depression induced by PP-2A inhibition occluded subsequent induction of LTD by
      conjunctive stimulation and was abolished by a calcium chelator or a protein
      kinase inhibitor, suggesting a shared molecular pathway and involvement of PP-2A
      in LTD induction.

PMID- 14699043
TI  - A functional Ni-Ni-[4Fe-4S] cluster in the monomeric acetyl-CoA synthase from
      Carboxydothermus hydrogenoformans.
AB  - In anaerobic microorganisms employing the acetyl-CoA pathway, acetyl-CoA synthase
      (ACS) and CO dehydrogenase (CODH) form a complex (ACS/CODH) that catalyzes the
      synthesis of acetyl-CoA from CO, a methyl group, and CoA. Previously, a [4Fe-4S]
      cubane bridged to a copper-nickel binuclear site (active site cluster A of the
      ACS component) was identified in the ACS(Mt)/CODH(Mt) from Moorella thermoacetica
      whereas another study revealed a nickel-nickel site in the open form of ACS(Mt),
      and a zink-nickel site in the closed form. The ACS(Ch) of the hydrogenogenic
      bacterium Carboxydothermus hydrogenoformans was found to exist as an 82.2-kDa
      monomer as well as in a 1:1 molar complex with the 73.3-kDa CODHIII(Ch).
      Homogeneous ACS(Ch) and ACS(Ch)/CODHIII(Ch) catalyzed the exchange between [1
      (14)C]acetyl-CoA and (12)CO with specific activities of 2.4 or 5.9 micromol of CO
      per min per mg, respectively, at 70 degrees C and pH 6.0. They also catalyzed the
      synthesis of acetyl-CoA from CO, methylcobalamin, corrinoid iron-sulfur protein,
      and CoA with specific activities of 0.14 or 0.91 micromol of acetyl-CoA formed
      per min per mg, respectively, at 70 degrees C and pH 7.3. The functional cluster
      A of ACS(Ch) contains a Ni-Ni-[4Fe-4S] site, in which the positions proximal and
      distal to the cubane are occupied by Ni ions. This result is apparent from a
      positive correlation of the Ni contents and negative correlations of the Cu or Zn
      contents with the acetyl-CoA/CO exchange activities of different preparations of
      monomeric ACS(Ch), a 2.2-A crystal structure of the dithionite-reduced monomer in
      an open conformation, and x-ray absorption spectroscopy.

PMID- 14699044
TI  - IL-13 receptor alpha 2 down-modulates granulomatous inflammation and prolongs
      host survival in schistosomiasis.
AB  - An important feature of many chronic parasitic infections is the ability of the
      invading pathogen and host to establish a compromise, which ensures successful
      parasitism without killing the infected host. For many helminth infections, down
      modulating the immune response is critical because persistent inflammation can
      become more damaging to the host than the invading pathogen itself. Such is the
      case with schistosomiasis mansoni, where chronic granulomatous inflammation in
      the liver causes portal hypertension, porto-pulmonary shunting, bleeding from
      collateral bypass vessels, and eventual death if not suppressed effectively.
      CD4(+) T helper type 2 cells (Th2) (secreting IL-4, IL-5, and IL-13) characterize
      the host response after Schistosoma mansoni infection, and recent studies have
      identified IL-13 as the principal mediator of hepatic fibrosis. Here, we show
      that the IL-13 receptor alpha 2 (IL-13R alpha 2) is a critical mediator of immune
      down-modulation, identifying the receptor as a life-sustaining off signal for
      chronic and pernicious inflammation in schistosomiasis.

PMID- 14699045
TI  - Hatching failure increases with severity of population bottlenecks in birds.
AB  - Severe bottlenecks can reduce genetic diversity and increase inbreeding as
      individuals are forced to mate with close relatives, but it is unknown at what
      minimum population size the negative fitness consequences of bottlenecks are
      expressed. The New Zealand avifauna contains a large number of species that have
      gone through bottlenecks of varying severity, providing an exceptional
      opportunity to test this question by using the comparative method. Using
      decreased hatchability as a measure of fitness costs, we found that hatching
      failure was significantly greater among both native and introduced species that
      had passed through bottlenecks of <150 individuals. Comparisons between pre- and
      postbottleneck populations of introduced species suggest that hatching problems
      arise even in populations founded by <600 individuals. Our study confirms that
      hatching failure is widespread and persistent among birds passing through severe
      bottlenecks and that the population sizes at which this fitness cost is expressed
      are several times greater than the number of individuals currently used to found
      most new populations of endangered species. We recommend that conservation
      managers revise the protocols they use for reintroductions or they may
      unwittingly reduce the long-term viability of the species they are trying to
      save.

PMID- 14699046
TI  - Entropic switch regulates myristate exposure in the HIV-1 matrix protein.
AB  - The myristoylated matrix protein (myr-MA) of HIV functions as a regulator of
      intracellular localization, targeting the Gag precursor polyprotein to lipid
      rafts in the plasma membrane during virus assembly and dissociating from the
      membrane during infectivity for nuclear targeting of the preintegration complex.
      Membrane release is triggered by proteolytic cleavage of Gag, and it has, until
      now, been believed that proteolysis induces a conformational change in myr-MA
      that sequesters the myristyl group. NMR studies reported here reveal that myr-MA
      adopts myr-exposed [myr(e)] and -sequestered [myr(s)] states, as anticipated.
      Unexpectedly, the tertiary structures of the protein in both states are very
      similar, with the sequestered myristyl group occupying a cavity that requires
      only minor conformational adjustments for insertion. In addition, myristate
      exposure is coupled with trimerization, with the myristyl group sequestered in
      the monomer and exposed in the trimer (K(assoc) = 2.5 +/- 0.6 x 10(8) M(-2)). The
      equilibrium constant is shifted approximately 20-fold toward the trimeric,
      myristate-exposed species in a Gag-like construct that includes the capsid
      domain, indicating that exposure is enhanced by Gag subdomains that promote self
      association. Our findings indicate that the HIV-1 myristyl switch is regulated
      not by mechanically induced conformational changes, as observed for other
      myristyl switches, but instead by entropic modulation of a preexisting
      equilibrium.

PMID- 14699047
TI  - The catalytic cycle of cytochrome c oxidase is not the sum of its two halves.
AB  - Membrane-bound cytochrome c oxidase catalyzes cell respiration in aerobic
      organisms and is a primary energy transducer in biology. The two halves of the
      catalytic cycle may be studied separately: in an oxidative phase, the enzyme is
      oxidized by O(2), and in a reductive phase, the oxidized enzyme is reduced before
      binding the next O(2) molecule. Here we show by time-resolved membrane potential
      and pH measurements with cytochrome oxidase liposomes that, with both phases in
      succession, two protons are translocated during each phase, one during each
      individual electron transfer step. However, when the reductive phase is not
      immediately preceded by oxidation, it follows a different reaction pathway no
      longer coupled to proton pumping. Metastable states with altered redox properties
      of the metal centers are accessed during turnover and relax when external
      electron donors are exhausted but recover after enzyme reduction and reoxidation
      by O(2). The efficiency of ATP synthesis might be regulated by switching between
      the two catalytic pathways.

PMID- 14699048
TI  - Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly
      fatal myeloproliferative disorder.
AB  - RAS mutations are common in myeloid malignancies; however, it is not known
      whether oncogenic RAS can initiate leukemia. We show that expressing mutant K
      Ras(G12D) protein from the endogenous murine locus rapidly induces a fatal
      myeloproliferative disorder with 100% penetrance characterized by tissue
      infiltration, hypersensitivity to growth factors, and hyperproliferation.
      Hematopoietic cells from diseased mice demonstrated increased levels of Ras-GTP,
      but effector kinases were not constitutively phosphorylated and responded
      normally to growth factors. Oncogenic RAS is sufficient to initiate myeloid
      leukemogenesis in mice, and this provides an in vivo system for biologic and
      preclinical studies.

PMID- 14699049
TI  - Demonstration of mammalian protein O-mannosyltransferase activity: coexpression
      of POMT1 and POMT2 required for enzymatic activity.
AB  - Defects in O-mannosylation of alpha-dystroglycan are thought to cause certain
      types of congenital muscular dystrophies with neuronal migration disorders. Among
      these muscular dystrophies, Walker-Warburg syndrome is caused by mutations in the
      gene encoding putative protein O-mannosyltransferase 1 (POMT1), which is
      homologous to yeast protein O-mannosyltransferases. However, there is no evidence
      that POMT1 has enzymatic activity. In this study, we first developed a method to
      detect protein O-mannosyltransferase activity in mammalian cells. Then, using
      this method, we showed that coexpression of both POMT1 and POMT2 (another gene
      homologous to yeast protein O-mannosyltransferases) was necessary for the enzyme
      activity, but expression of either POMT1 or POMT2 alone was insufficient. The
      requirement of an active enzyme complex of POMT1 and POMT2 suggests that the
      regulation of protein O-mannosylation is complex. Further, protein O
      mannosylation appears to be required for normal structure and function of alpha
      dystroglycan in muscle and brain. In view of the potential importance of this
      form of glycosylation for a number of developmental and neurobiological
      processes, the ability to assay mammalian protein O-mannosyltransferase activity
      should greatly facilitate progress in the identification and localization of O
      mannosylated proteins and the elucidation of their functional roles.

PMID- 14699050
TI  - Residual integrated viral DNA after hepadnavirus clearance by nucleoside analog
      therapy.
AB  - We determined the frequency of integrated viral DNA in the livers of three
      woodchucks chronically infected with the woodchuck hepatitis virus before and
      during 30 weeks of therapy with the nucleoside analog L-FMAU [1-(2-fluoro-5
      methyl-beta, L-arabinofuranosyl)uracil, clevudine]. We found that although viral
      covalently closed circular DNA declined 20- to 100-fold, integrated viral DNA
      showed no discernable decrease over the course of treatment. Thus,
      chemotherapeutic clearance of covalently closed circular DNA did not involve the
      replacement of the infected hepatocyte population with uninfected progenitors,
      but rather, uninfected hepatocytes in the treated liver were derived from the
      infected hepatocyte population. The frequency of integrated DNA in chronically
      infected woodchucks was found to be 1 or 2 orders of magnitude higher than that
      in transiently infected woodchucks, implying that integration and other genomic
      damage accumulate over the duration of infection. Our results indicate that
      genetic changes from this damage remain in the liver even while virus infection
      is cleared and argue for early antiviral intervention in chronic hepatitis.

PMID- 14699051
TI  - Analysis of C5a-mediated chemotaxis by lentiviral delivery of small interfering
      RNA.
AB  - Immune cells respond to chemotactic signals by means of G protein-coupled
      receptors. Attempts to elucidate the function of specific G protein family
      members in these responses is complicated by redundancy among the different G
      protein isoforms. We have used lentiviral-based RNA interference to eliminate
      expression of specific G protein subunits selectively in J774A.1 mouse
      macrophages. The chemotactic response to the complement factors C5a and C3a is
      ablated in cells lacking G beta(2) but is unaffected in cells lacking G beta(1),
      G alpha i(2), or G alpha i(3). Similarly, the C5a-mediated calcium response of
      single cells is either absent or significantly delayed and weakened by G beta(2)
      knockdown. Assessment of Akt1 phosphorylation levels in response to C5a shows
      rapid and sustained phosphorylation in both wild-type cells and cells lacking G
      beta(1). Cells lacking G beta(2) retain the rapid response but cannot sustain
      phospho-Akt1 levels. The phenotype of cells lacking G beta(2) can be reversed by
      overexpression of either human G beta(2) or mouse G beta(1). These data
      demonstrate the usefulness of lentiviral-based RNA interference in the systematic
      analysis of a signaling pathway, and they suggest that in J774A.1 cells, G
      beta(2)-derived G beta gamma is the most effective mediator of chemotaxis to C5a.

PMID- 14699052
TI  - The chitinolytic cascade in Vibrios is regulated by chitin oligosaccharides and a
      two-component chitin catabolic sensor/kinase.
AB  - Chitin, a highly insoluble polymer of GlcNAc, is produced in massive quantities
      in the marine environment. Fortunately for survival of aquatic ecosystems, chitin
      is rapidly catabolized by marine bacteria. Here we describe a bacterial two
      component hybrid sensor/kinase (of the ArcB type) that rigorously controls
      expression of approximately 50 genes, many involved in chitin degradation. The
      sensor gene, chiS, was identified in Vibrio furnissii and Vibrio cholerae
      (predicted amino acid sequences, full-length: 84% identical, 93% similar).
      Mutants of chiS grew normally on GlcNAc but did not express extracellular
      chitinase, a specific chitoporin, or beta-hexosaminidases, nor did they exhibit
      chemotaxis, transport, or growth on chitin oligosaccharides such as (GlcNAc)(2).
      Expression of these systems requires three components: wild-type chiS; a
      periplasmic high-affinity chitin oligosaccharide, (GlcNAc)(n) (n > 1), binding
      protein (CBP); and the environmental signal, (GlcNAc)(n). Our data are consistent
      with the following model. In the uninduced state, CBP binds to the periplasmic
      domain of ChiS and "locks" it into the minus conformation. The environmental
      signal, (GlcNAc)(n), dissociates the complex by binding to CBP, releasing ChiS,
      yielding the plus phenotype (expression of chitinolytic genes). In V. cholerae, a
      cluster of 10 contiguous genes (VC0620-VC0611) apparently comprise a (GlcNAc)(2)
      catabolic operon. CBP is encoded by the first, VC0620, whereas VC0619-VC0616
      encode a (GlcNAc)(2) ABC-type permease. Regulation of chiS requires expression of
      CBP but not (GlcNAc)(2) transport. (GlcNAc)(n) is suggested to be essential for
      signaling these cells that chitin is in the microenvironment.

PMID- 14699053
TI  - Soot climate forcing via snow and ice albedos.
AB  - Plausible estimates for the effect of soot on snow and ice albedos (1.5% in the
      Arctic and 3% in Northern Hemisphere land areas) yield a climate forcing of +0.3
      W/m(2) in the Northern Hemisphere. The "efficacy" of this forcing is
      approximately 2, i.e., for a given forcing it is twice as effective as CO(2) in
      altering global surface air temperature. This indirect soot forcing may have
      contributed to global warming of the past century, including the trend toward
      early springs in the Northern Hemisphere, thinning Arctic sea ice, and melting
      land ice and permafrost. If, as we suggest, melting ice and sea level rise define
      the level of dangerous anthropogenic interference with the climate system, then
      reducing soot emissions, thus restoring snow albedos to pristine high values,
      would have the double benefit of reducing global warming and raising the global
      temperature level at which dangerous anthropogenic interference occurs. However,
      soot contributions to climate change do not alter the conclusion that
      anthropogenic greenhouse gases have been the main cause of recent global warming
      and will be the predominant climate forcing in the future.

PMID- 14699054
TI  - Defective lysosomal targeting of activated fibroblast growth factor receptor 3 in
      achondroplasia.
AB  - Mutations of fibroblast growth factor receptor 3 (FGFR3) are responsible for
      achondroplasia (ACH) and related dwarfing conditions in humans. The pathogenesis
      involves constitutive activation of FGFR3, which inhibits proliferation and
      differentiation of growth plate chondrocytes. Here we report that activating
      mutations in FGFR3 increase the stability of the receptor. Our results suggest
      that the mutations disrupt c-Cbl-mediated ubiquitination that serves as a
      targeting signal for lysosomal degradation and termination of receptor signaling.
      The defect allows diversion of actively signaling receptors from lysosomes to a
      recycling pathway where their survival is prolonged, and, as a result, their
      signaling capacity is increased. The lysosomal targeting defect is additive to
      other mechanisms proposed to explain the pathogenesis of ACH.

PMID- 14699055
TI  - Endoplasmic reticulum quality control of unassembled iron transporter depends on
      Rer1p-mediated retrieval from the golgi.
AB  - Endoplasmic reticulum (ER) quality control is a conserved process by which
      misfolded or unassembled proteins are selectively retained in the endoplasmic
      reticulum (ER). Failure in oligomerization of multisubunit membrane proteins is
      one of the events that triggers ER quality control. The transmembrane domains
      (TMDs) of unassembled subunits are determinants of ER retention in many cases,
      although the mechanism of the TMD-mediated sorting of unassembled subunits
      remains elusive. We studied a yeast iron transporter complex on the cell surface
      as a new model system for ER quality control. When Fet3p, a transmembrane
      subunit, is not assembled with the other membrane subunit, Ftr1p, unassembled
      Fet3p is exclusively localized to the ER at steady state. The TMD of Fet3p
      contains a determinant for this process. However, pulse-chase analysis and in
      vitro budding assays indicate that unassembled Fet3p rapidly escapes from the ER.
      Furthermore, Rer1p, a retrieval receptor for ER-resident membrane proteins in the
      Golgi, is responsible for the TMD-dependent ER retrieval of unassembled Fet3p.
      These findings provide clear evidence that the ER quality control of unassembled
      membrane proteins can be achieved by retrieval from the Golgi and that Rer1p
      serves as a specific sorting receptor in this process.

PMID- 14699056
TI  - The alpha- and beta'-COP WD40 domains mediate cargo-selective interactions with
      distinct di-lysine motifs.
AB  - Coatomer is required for the retrieval of proteins from an early Golgi
      compartment back to the endoplasmic reticulum. The WD40 domain of alpha-COP is
      required for the recruitment of KKTN-tagged proteins into coatomer-coated
      vesicles. However, lack of the domain has only minor effects on growth in yeast.
      Here, we show that the WD40 domain of beta'-COP is required for the recycling of
      the KTKLL-tagged Golgi protein Emp47p. The protein is degraded more rapidly in
      cells with a point mutation in the WD40 domain of beta'-COP (sec27-95) or in
      cells lacking the domain altogether, whereas a point mutation in the Clathrin
      Heavy Chain Repeat (sec27-1) does not affect the turnover of Emp47p. Lack of the
      WD40 domain of beta'-COP has only minor effects on growth of yeast cells;
      however, absence of both WD40 domains of alpha- and beta'-COP is lethal. Two
      hybrid studies together with our analysis of the maturation of KKTN-tagged
      invertase and the turnover of Emp47p in alpha- and beta'-COP mutants suggest that
      the two WD40 domains of alpha- and beta'-COP bind distinct but overlapping sets
      of di-lysine signals and hence both contribute to recycling of proteins with di
      lysine signals.

PMID- 14699057
TI  - Mitochondrial localization of the mevalonate pathway enzyme 3-Hydroxy-3-methyl
      glutaryl-CoA reductase in the Trypanosomatidae.
AB  - 3-Hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) is a key enzyme in the sterol
      biosynthesis pathway, but its subcellular distribution in the Trypanosomatidae
      family is somewhat controversial. Trypanosoma cruzi and Leishmania HMGRs are
      closely related in their catalytic domains to bacterial and eukaryotic enzymes
      described but lack an amino-terminal domain responsible for the attachment to the
      endoplasmic reticulum. In the present study, digitonin-titration experiments
      together with immunoelectron microscopy were used to establish the intracellular
      localization of HMGR in these pathogens. Results obtained with wild-type cells
      and transfectants overexpressing the enzyme established that HMGR in both T.
      cruzi and Leishmania major is localized primarily in the mitochondrion and that
      elimination of the mitochondrial targeting sequence in Leishmania leads to
      protein accumulation in the cytosolic compartment. Furthermore, T. cruzi HMGR is
      efficiently targeted to the mitochondrion in yeast cells. Thus, when the gene
      encoding T. cruzi HMGR was expressed in a hmg1 hmg2 mutant of Saccharomyces
      cerevisiae, the mevalonate auxotrophy of mutant cells was relieved, and
      immunoelectron analysis showed that the parasite enzyme exhibits a mitochondrial
      localization, suggesting a conservation between the targeting signals of both
      organisms.

PMID- 14699058
TI  - In vivo analysis of autophagy in response to nutrient starvation using transgenic
      mice expressing a fluorescent autophagosome marker.
AB  - Macroautophagy mediates the bulk degradation of cytoplasmic components. It
      accounts for the degradation of most long-lived proteins: cytoplasmic
      constituents, including organelles, are sequestered into autophagosomes, which
      subsequently fuse with lysosomes, where degradation occurs. Although the possible
      involvement of autophagy in homeostasis, development, cell death, and
      pathogenesis has been repeatedly pointed out, systematic in vivo analysis has not
      been performed in mammals, mainly because of a limitation of monitoring methods.
      To understand where and when autophagy occurs in vivo, we have generated
      transgenic mice systemically expressing GFP fused to LC3, which is a mammalian
      homologue of yeast Atg8 (Aut7/Apg8) and serves as a marker protein for
      autophagosomes. Fluorescence microscopic analyses revealed that autophagy is
      differently induced by nutrient starvation in most tissues. In some tissues,
      autophagy even occurs actively without starvation treatments. Our results suggest
      that the regulation of autophagy is organ dependent and the role of autophagy is
      not restricted to the starvation response. This transgenic mouse model is a
      useful tool to study mammalian autophagy.

PMID- 14699059
TI  - Repression of Na,K-ATPase beta1-subunit by the transcription factor snail in
      carcinoma.
AB  - The Na,K-ATPase consists of two essential alpha- and beta-subunits and regulates
      the intracellular Na+ and K+ homeostasis. Although the alpha-subunit contains the
      catalytic activity, it is not active without functional beta-subunit. Here, we
      report that poorly differentiated carcinoma cell lines derived from colon,
      breast, kidney, and pancreas show reduced expression of the Na,K-ATPase beta1
      subunit. Decreased expression of beta1-subunit in poorly differentiated carcinoma
      cell lines correlated with increased expression of the transcription factor Snail
      known to down-regulate E-cadherin. Ectopic expression of Snail in well
      differentiated epithelial cell lines reduced the protein levels of E-cadherin and
      beta1-subunit and induced a mesenchymal phenotype. Reduction of Snail expression
      in a poorly differentiated carcinoma cell line by RNA interference increased the
      levels of Na,K-ATPase beta1-subunit. Furthermore, Snail binds to a noncanonical E
      box in the Na,K-ATPase beta1-subunit promoter and suppresses its promoter
      activity. These results suggest that down-regulation of Na,K-ATPase beta1-subunit
      and E-cadherin by Snail are associated with events leading to epithelial to
      mesenchymal transition.

PMID- 14699060
TI  - Methionine sulfoxide reduction in mammals: characterization of methionine-R
      sulfoxide reductases.
AB  - Methionine residues in proteins are susceptible to oxidation by reactive oxygen
      species, but can be repaired via reduction of the resulting methionine sulfoxides
      by methionine-S-sulfoxide reductase (MsrA) and methionine-R-sulfoxide reductase
      (MsrB). However, the identity of all methionine sulfoxide reductases involved,
      their cellular locations and relative contributions to the overall pathway are
      poorly understood. Here, we describe a methionine-R-sulfoxide reduction system in
      mammals, in which two MsrB homologues were previously described. We found that
      human and mouse genomes possess three MsrB genes and characterized their protein
      products, designated MsrB1, MsrB2, and MsrB3. MsrB1 (Selenoprotein R) was present
      in the cytosol and nucleus and exhibited the highest methionine-R-sulfoxide
      reductase activity because of the presence of selenocysteine (Sec) in its active
      site. Other mammalian MsrBs contained cysteine in place of Sec and were less
      catalytically efficient. MsrB2 (CBS-1) resided in mitochondria. It had high
      affinity for methionine-R-sulfoxide, but was inhibited by higher concentrations
      of the substrate. The human MsrB3 gene gave rise to two protein forms, MsrB3A and
      MsrB3B. These were generated by alternative splicing that introduced contrasting
      N-terminal and C-terminal signals, such that MsrB3A was targeted to the
      endoplasmic reticulum and MsrB3B to mitochondria. We found that only
      mitochondrial forms of mammalian MsrBs (MsrB2 and MsrB3B) could compensate for
      MsrA and MsrB deficiency in yeast. All mammalian MsrBs belonged to a group of
      zinc-containing proteins. The multiplicity of MsrBs contrasted with the presence
      of a single mammalian MsrA gene as well as with the occurrence of single MsrA and
      MsrB genes in yeast, fruit flies, and nematodes. The data suggested that
      different cellular compartments in mammals maintain a system for repair of
      oxidized methionine residues and that this function is tuned in enzyme- and
      stereo-specific manner.

PMID- 14699061
TI  - Coactivation of Rac1 and Cdc42 at lamellipodia and membrane ruffles induced by
      epidermal growth factor.
AB  - A major function of Rho-family GTPases is to regulate the organization of the
      actin cytoskeleton; filopodia, lamellipodia, and stress fiber are regarded as
      typical phenotypes of the activated Cdc42, Rac, and Rho, respectively. Using
      probes based on fluorescent resonance energy transfer, we report on the
      spatiotemporal regulation of Rac1 and Cdc42 at lamellipodia and membrane ruffles.
      In epidermal growth factor (EGF)-stimulated Cos1 and A431 cells, both Rac1 and
      Cdc42 were activated diffusely at the plasma membrane, followed by lamellipodial
      protrusion and membrane ruffling. Although Rac1 activity subsided rapidly, Cdc42
      activity was sustained at lamellipodia. A critical role of Cdc42 in these EGF
      induced morphological changes was demonstrated as follows. First, phorbol 12
      myristate 13-acetate, which activated Rac1 but not Cdc42, could not induce full
      grown lamellipodia in Cos1 cells. Second, a GTPase-activating protein for Cdc42,
      KIAA1204/CdGAP, inhibited lamellipodial protrusion and membrane ruffling without
      interfering with Rac1 activation. Third, expression of the Cdc42-binding domain
      of N-WASP inhibited the EGF-induced morphological changes. Therefore, Rac1 and
      Cdc42 seem to synergistically induce lamellipodia and membrane ruffles in EGF
      stimulated Cos1 cells and A431 cells.

PMID- 14699062
TI  - A cell-specific transgenic approach in Xenopus reveals the importance of a
      functional p24 system for a secretory cell.
AB  - The p24alpha, -beta, -gamma, and -delta proteins are major multimeric
      constituents of cycling endoplasmic reticulum-Golgi transport vesicles and are
      thought to be involved in protein transport through the early secretory pathway.
      In this study, we targeted transgene overexpression of p24delta2 specifically to
      the Xenopus intermediate pituitary melanotrope cell that is involved in
      background adaptation of the animal and produces high levels of its major
      secretory cargo proopiomelanocortin (POMC). The transgene product effectively
      displaced the endogenous p24 proteins, resulting in a melanotrope cell p24 system
      that consisted predominantly of the transgene p24delta2 protein. Despite the
      severely distorted p24 machinery, the subcellular structures as well as the level
      of POMC synthesis were normal in these cells. However, the number and pigment
      content of skin melanophores were reduced, impairing the ability of the
      transgenic animal to fully adapt to a black background. This physiological effect
      was likely caused by the affected profile of POMC-derived peptides observed in
      the transgenic melanotrope cells. Together, our results suggest that in the early
      secretory pathway an intact p24 system is essential for efficient secretory cargo
      transport or for supplying cargo carriers with the correct protein machinery to
      allow proper secretory protein processing.

PMID- 14699063
TI  - Positive role of IQGAP1, an effector of Rac1, in actin-meshwork formation at
      sites of cell-cell contact.
AB  - The small guanosine triphosphatase Rac1 is activated by E-cadherin-mediated cell
      cell adhesion and is required for the accumulation of actin filaments, E
      cadherin, and beta-catenin at sites of cell-cell contact. However, the modes of
      activation and action of Rac1 remain to be clarified. We here found that
      suppression of IQGAP1, an actin-binding protein and an effector of Rac1, by small
      interfering RNA apparently reduced the accumulation of actin filaments, E
      cadherin, and beta-catenin at sites of cell-cell contact in Madin-Darby canine
      kidney II epithelial cells under the conditions in which knockdown of Rac1
      reduced them. Knockdown of Rac1 did not affect the localization of these
      junctional components in cells expressing a constitutively active IQGAP1 mutant
      defective in Rac1/Cdc42 binding. Knockdown of either Rac1 or IQGAP1 accelerated
      the 12-O-tetradecanoylphorbol-13-acetate-induced cell-cell dissociation. The
      basal Rac1 activity, which was maintained by E-cadherin-mediated cell-cell
      adhesion, was inhibited in the IQGAP1-knocked down cells, whereas the Rac1
      activity was increased in the cells overexpressing IQGAP1. Together, these
      results indicate that Rac1 enhances the accumulation of actin filaments, E
      cadherin, and beta-catenin by acting on IQGAP1 and suggest that there exists a
      positive feedback loop comprised of "E-cadherin-mediated cell-cell adhesion -->
      Rac1 activation --> actin-meshwork formation by IQGAP1 --> increasing E-cadherin
      mediated cell-cell adhesion."

PMID- 14699064
TI  - Depletion of centromeric MCAK leads to chromosome congression and segregation
      defects due to improper kinetochore attachments.
AB  - The complex behavior of chromosomes during mitosis is accomplished by precise
      binding and highly regulated polymerization dynamics of kinetochore microtubules.
      Previous studies have implicated Kin Is, unique kinesins that depolymerize
      microtubules, in regulating chromosome positioning. We have characterized the
      immunofluorescence localization of centromere-bound MCAK and found that MCAK
      localized to inner kinetochores during prophase but was predominantly centromeric
      by metaphase. Interestingly, MCAK accumulated at leading kinetochores during
      congression but not during segregation. We tested the consequences of MCAK
      disruption by injecting a centromere dominant-negative protein into prophase
      cells. Depletion of centromeric MCAK led to reduced centromere stretch, delayed
      chromosome congression, alignment defects, and severe missegregation of
      chromosomes. Rates of chromosome movement were unchanged, suggesting that the
      primary role of MCAK is not to move chromosomes. Furthermore, we found that
      disruption of MCAK leads to multiple kinetochore-microtubule attachment defects,
      including merotelic, syntelic, and combined merotelic-syntelic attachments. These
      findings reveal an essential role for Kin Is in prevention and/or correction of
      improper kinetochore-microtubule attachments.

PMID- 14699066
TI  - X-ray tomography generates 3-D reconstructions of the yeast, saccharomyces
      cerevisiae, at 60-nm resolution.
AB  - We examined the yeast, Saccharomyces cerevisiae, using X-ray tomography and
      demonstrate unique views of the internal structural organization of these cells
      at 60-nm resolution. Cryo X-ray tomography is a new imaging technique that
      generates three-dimensional (3-D) information of whole cells. In the energy range
      of X-rays used to examine cells, organic material absorbs approximately an order
      of magnitude more strongly than water. This produces a quantifiable natural
      contrast in fully hydrated cells and eliminates the need for chemical fixatives
      or contrast enhancement reagents to visualize cellular structures. Because
      proteins can be localized in the X-ray microscope using immunogold labeling
      protocols (Meyer-Ilse et al., 2001. J. Microsc. 201, 395-403), tomography enables
      3-D molecular localization. The time required to collect the data for each cell
      shown here was <15 min and has recently been reduced to 3 min, making it possible
      to examine numerous yeast and to collect statistically significant high
      resolution data. In this video essay, we show examples of 3-D tomographic
      reconstructions of whole yeast and demonstrate the power of this technology to
      obtain quantifiable information from whole, hydrated cells.

PMID- 14699065
TI  - Specific N-glycans direct apical delivery of transmembrane, but not soluble or
      glycosylphosphatidylinositol-anchored forms of endolyn in Madin-Darby canine
      kidney cells.
AB  - The sialomucin endolyn is a transmembrane protein with a unique trafficking
      pattern in polarized Madin-Darby canine kidney cells. Despite the presence of a
      cytoplasmic tyrosine motif that, in isolation, is sufficient to mediate
      basolateral sorting of a reporter protein, endolyn predominantly traverses the
      apical surface en route to lysosomes. Apical delivery of endolyn is disrupted in
      tunicamycin-treated cells, implicating a role for N-glycosylation in apical
      sorting. Site-directed mutagenesis of endolyn's eight N-glycosylation sites was
      used to identify two N-glycans that seem to be the major determinants for
      efficient apical sorting of the protein. In addition, apical delivery of endolyn
      was disrupted when terminal processing of N-glycans was blocked using glycosidase
      inhibitors. Missorting of endolyn occurred independently of the presence or
      absence of the basolateral sorting signal, because apical delivery was also
      inhibited by tunicamycin when the cytoplasmic tyrosine motif was mutated.
      However, we found that apical secretion of a soluble mutant of endolyn was N
      glycan independent, as was delivery of glycosylphosphatidylinositol-anchored
      endolyn. Thus, specific N-glycans are only essential for the apical sorting of
      transmembrane endolyn, suggesting fundamental differences in the mechanisms by
      which soluble, glycosylphosphatidylinositol-anchored, and transmembrane proteins
      are sorted.

PMID- 14699067
TI  - A single amino acid change (Asp 53 --> Ala53) converts Survivin from anti
      apoptotic to pro-apoptotic.
AB  - Survivin is a member of the inhibitor of apoptosis protein (IAP) family that has
      been implicated in both apoptosis inhibition and cell cycle control. Recently,
      Survivin has attracted growing attention because of its tumor-specific expression
      and potential applications in tumor therapy. However, its inhibitory mechanism
      and subcellular localization remain controversial. Here, we report a novel
      Survivin mutant Surv-D53A, which displays a function opposite to Survivin and a
      distinctive subcellular distribution compared with its wild-type counterpart.
      Surv-D53A was shown to induce apoptosis in a p53-independent manner, indicating
      that tumor suppressor p53 is not involved in its apoptosis pathway. Surv-D53A was
      shown to markedly sensitize apoptosis induced by TRAIL, doxorubicin, and RIP3. We
      also demonstrated that similar to wild-type Survivin, Surv-D53A was localized in
      cytoplasm in interphase and to midbody at telophase. However, it fails to
      colocalize in chromosomes with Aurora-B in metaphase as wt-Survivin. Surv-D53A
      mutant is less stable than wt-Survivin and is degraded more rapidly by ubiquitin
      proteasome pathway. Additionally, we found that Surv-D53A interacts with wt
      Survivin to form heterodimer or with itself to form mutant homodimer, which may
      account for the loss of its antiapoptotic function. Finally, unlike
      Survivin*Survivin, neither Surv-D53A*Survivin nor Surv-D53A*Surv-D53A is able to
      bind to Smac/DIABLO, which may explain the underlying mechanism for its
      abolishment of antiapoptotic activity of Survivin.

PMID- 14699068
TI  - Tumor necrosis factor-alpha promotes survival of opossum kidney cells via Cdc42
      induced phospholipase C-gamma1 activation and actin filament redistribution.
AB  - Although the renal proximal tubular epithelial cells are targeted in a variety of
      inflammatory diseases of the kidney, the signaling mechanism by which tumor
      necrosis factor (TNF)-alpha exerts its effects in these cells remains unclear.
      Here, we report that TNF-alpha elicits antiapoptotic effects in opossum kidney
      cells and that this response is mediated via actin redistribution through a novel
      signaling mechanism. More specifically, we show that TNF-alpha prevents apoptosis
      by inhibiting the activity of caspase-3 and this effect depends on actin
      polymerization state and nuclear factor-kappaB activity. We also demonstrate that
      the signaling cascade triggered by TNF-alpha is governed by the
      phosphatidylinositol-3 kinase, Cdc42/Rac1, and phospholipase (PLC)-gamma1. In
      this signaling cascade, Cdc42 was found to be selectively essential for PLC
      gamma1 activation, whereas phosphatidylinositol-3,4,5-triphosphate alone is not
      sufficient to activate the phospholipase. Moreover, PLC-gamma1 was found to
      associate in vivo with the small GTPase(s). Interestingly, PLC-gamma1 was
      observed to associate with constitutively active (CA) Cdc42V12, but not with CA
      Rac1V12, whereas no interaction was detected with Cdc42(T17N). The inactive
      Cdc42(T17N) and the PLC-gamma1 inhibitor U73122 prevented actin redistribution
      and depolymerization, confirming that both signaling molecules are responsible
      for the reorganization of actin. Additionally, the actin filament stabilizer
      phallacidin potently blocked the nuclear translocation of nuclear factor-kappaB
      and its binding activity, resulting in abrogation of the TNF-alpha-induced
      inhibition of caspase-3. To conclude, our findings suggest that actin may play a
      pivotal role in the response of opossum kidney cells to TNF-alpha and implicate
      Cdc42 in directly regulating PLC-gamma1 activity.

PMID- 14699069
TI  - Interaction with Smad4 is indispensable for suppression of BMP signaling by c
      Ski.
AB  - c-Ski is a transcriptional corepressor that interacts strongly with Smad2, Smad3,
      and Smad4 but only weakly with Smad1 and Smad5. Through binding to Smad proteins,
      c-Ski suppresses signaling of transforming growth factor-beta (TGF-beta) as well
      as bone morphogenetic proteins (BMPs). In the present study, we found that a
      mutant of c-Ski, termed c-Ski (ARPG) inhibited TGF-beta/activin signaling but not
      BMP signaling. Selectivity was confirmed in luciferase reporter assays and by
      determination of cellular responses in mammalian cells (BMP-induced osteoblastic
      differentiation of C2C12 cells and TGF-beta-induced epithelial-to-mesenchymal
      transdifferentiation of NMuMG cells) and Xenopus embryos. The ARPG mutant
      recruited histone deacetylases 1 (HDAC1) to the Smad3-Smad4 complex but not to
      the Smad1/5-Smad4 complex. c-Ski (ARPG) was unable to interact with Smad4, and
      the selective loss of suppression of BMP signaling by c-Ski (ARPG) was attributed
      to the lack of Smad4 binding. We also found that c-Ski interacted with Smad3 or
      Smad4 without disrupting Smad3-Smad4 heteromer formation. c-Ski (ARPG) would be
      useful for selectively suppressing TGF-beta/activin signaling.

PMID- 14699070
TI  - ago1 and dcr1, two core components of the RNA interference pathway, functionally
      diverge from rdp1 in regulating cell cycle events in Schizosaccharomyces pombe.
AB  - In the fission yeast Schizosaccharomyces pombe, three genes that function in the
      RNA interference (RNAi) pathway, ago1+, dcr1+, and rdp1+, have recently been
      shown to be important for timely formation of heterochromatin and accurate
      chromosome segregation. In the present study, we present evidence that null
      mutants for ago1+ and dcr1+ but not rdp1+, exhibit abnormal cytokinesis, cell
      cycle arrest deficiencies, and mating defects. Subsequent analyses showed that
      ago1+ and dcr1+ are required for regulated hyperphosphorylation of Cdc2 when
      encountering genotoxic insults. Because rdp1+ is dispensable for this process,
      the functions of ago1+ and dcr1+ in this pathway are presumably independent of
      their roles in RNAi-mediated heterochromatin formation and chromosome
      segregation. This was further supported by the finding that ago1+ is a multicopy
      suppressor of the S-M checkpoint deficiency and cytokinesis defects associated
      with loss of Dcr1 function, but not for the chromosome segregation defects of
      this mutant. Accordingly, we conclude that Dcr1-dependent production of small
      interfering RNAs is not required for enactment and/or maintenance of certain cell
      cycle checkpoints and that Ago1 and Dcr1 functionally diverge from Rdp1 to
      control cell cycle events in fission yeast. Finally, exogenous expression of
      hGERp95/EIF2C2/hAgo2, a human Ago1 homolog implicated in posttranscriptional gene
      silencing, compensated for the loss of ago1+ function in S. pombe. This suggests
      that PPD proteins may also be important for regulation of cell cycle events in
      higher eukaryotes.

PMID- 14699071
TI  - Induction of apoptosis in starfish eggs requires spontaneous inactivation of MAPK
      (extracellular signal-regulated kinase) followed by activation of p38MAPK.
AB  - Mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinase)
      prevents DNA replication and parthenogenesis in maturing oocytes. After the
      meiotic cell cycle in starfish eggs, MAPK activity is maintained until
      fertilization. When eggs are fertilized, inactivation of MAPK occurs, allowing
      development to proceed. Without fertilization, highly synchronous apoptosis of
      starfish eggs starts 10 h after germinal vesicle breakdown, which varies
      according to season and individual animals. For induction of the apoptosis, MAPK
      should be activated for a definite period, called the MAPK-dependent period,
      during which eggs develop competence to die, although the exact duration of the
      period was unclear. In this study, we show that the duration of the MAPK
      dependent period was approximately 8 h. Membrane blebbing occurred approximately
      2 h after the MAPK-dependent period. Surprisingly, when MAPK was inhibited by
      U0126 after the MAPK-dependent period, activation of caspase-3 occurred earlier
      than in the control eggs. Thus, inactivation of MAPK is a prerequisite for
      apoptosis. Also, even in the absence of the inhibitor, MAPK was inactivated
      spontaneously when eggs began to bleb, indicating that inactivation of MAPK after
      the MAPK-dependent period acts upstream of caspase-3. Inactivation of MAPK also
      resulted in the activation of p38MAPK, which may contribute to apoptotic body
      formation.

PMID- 14699072
TI  - Estradiol and selective estrogen receptor modulators differentially regulate
      target genes with estrogen receptors alpha and beta.
AB  - Estrogens and selective estrogen receptor modulators (SERMs) interact with
      estrogen receptor (ER) alpha and beta to activate or repress gene transcription.
      To understand how estrogens and SERMs exert tissue-specific effects, we performed
      microarray analysis to determine whether ERalpha or ERbeta regulate different
      target genes in response to estrogens and SERMs. We prepared human U2OS
      osteosarcoma cells that are stably transfected with a tetracycline-inducible
      vector to express ERalpha or ERbeta. Western blotting, immunohistochemistry, and
      immunoprecipitation studies confirmed that U2OS-ERalpha cells synthesized only
      ERalpha and that U2OS-ERbeta cells expressed exclusively ERbeta. U2OS-ERalpha and
      U2OS-ERbeta cells were treated either with 17beta-estradiol (E2), raloxifene, and
      tamoxifen for 18 h. Labeled cRNAs were hybridized with U95Av2 GeneChips
      (Affymetrix). A total of 228, 190, and 236 genes were significantly activated or
      repressed at least 1.74-fold in U2OS-ERalpha and U2OS-ERbeta cells by E2,
      raloxifene, and tamoxifen, respectively. Most genes regulated in ERalpha cells in
      response to E2, raloxifene, and tamoxifen were distinct from those regulated in
      ERbeta cells. Only 38 of the 228 (17%) genes were regulated by E2 in both U2OS
      ERalpha and U2OS-ERbeta cells. Raloxifene and tamoxifen regulated only 27% of the
      same genes in both the ERalpha and ERbeta cells. A subset of genes involved in
      bone-related activities regulated by E2, raloxifene, and tamoxifen were also
      distinct. Our results demonstrate that most genes regulated by ERalpha are
      distinct from those regulated by ERbeta in response to E2 and SERMs. These
      results indicate that estrogens and SERMs exert tissue-specific effects by
      regulating unique sets of targets genes through ERalpha and ERbeta

PMID- 14699073
TI  - Nonmuscle myosin IIb is involved in the guidance of fibroblast migration.
AB  - Although myosin II is known to play an important role in cell migration, little
      is known about its specific functions. We have addressed the function of one of
      the isoforms of myosin II, myosin IIB, by analyzing the movement and mechanical
      characteristics of fibroblasts where this protein has been ablated by gene
      disruption. Myosin IIB null cells displayed multiple unstable and disorganized
      protrusions, although they were still able to generate a large fraction of
      traction forces when cultured on flexible polyacrylamide substrates. However, the
      traction forces were highly disorganized relative to the direction of cell
      migration. Analysis of cell migration patterns indicated an increase in speed and
      decrease in persistence, which were likely responsible for the defects in
      directional movements as demonstrated with Boyden chambers. In addition, unlike
      control cells, mutant cells failed to respond to mechanical signals such as
      compressing forces and changes in substrate rigidity. Immunofluorescence staining
      indicated that myosin IIB was localized preferentially along stress fibers in the
      interior region of the cell. Our results suggest that myosin IIB is involved not
      in propelling but in directing the cell movement, by coordinating protrusive
      activities and stabilizing the cell polarity.

PMID- 14699074
TI  - A novel role of nectins in inhibition of the E-cadherin-induced activation of Rac
      and formation of cell-cell adherens junctions.
AB  - Nectins are Ca(2+)-independent immunoglobulin (Ig)-like cell-cell adhesion
      molecules. The trans-interactions of nectins recruit cadherins to the nectin
      based cell-cell adhesion, resulting in formation of cell-cell adherens junctions
      (AJs) in epithelial cells and fibroblasts. The trans-interaction of E-cadherin
      induces activation of Rac small G protein, whereas the trans-interactions of
      nectins induce activation of not only Rac but also Cdc42 small G protein. We
      showed by the fluorescent resonance energy transfer (FRET) imaging that the trans
      interaction of E-cadherin induced dynamic activation and inactivation of Rac,
      which led to dynamic formation and retraction of lamellipodia. Moreover, we found
      here that the nectins, which did not trans-interact with other nectins (non-trans
      interacting nectins), inhibited the E-cadherin-induced activation of Rac and
      reduced the velocity of the formation of the E-cadherin-based cell-cell AJs. The
      inhibitory effect of non-trans-interacting nectins was suppressed by the
      activation of Cdc42 induced by the trans-interactions of nectins. These results
      indicate a novel role of nectins in regulation of the E-cadherin-induced
      activation of Rac and formation of cell-cell AJs.

PMID- 14699075
TI  - Routing of Hansenula polymorpha alcohol oxidase: an alternative peroxisomal
      protein-sorting machinery.
AB  - Import of Hansenula polymorpha alcohol oxidase (AO) into peroxisomes is dependent
      on the PTS1 receptor, HpPex5p. The PTS1 of AO (-LARF) is sufficient to direct
      reporter proteins to peroxisomes. To study AO sorting in more detail, strains
      producing mutant AO proteins were constructed. AO containing a mutation in the
      FAD binding fold was mislocalized to the cytosol. This indicates that the PTS1 of
      AO is not sufficient for import of AO. AO protein in which the PTS1 was destroyed
      (-LARA) was normally sorted to peroxisomes. Moreover, C-terminal deletions of up
      to 16 amino acids did not significantly affect AO import, indicating that the
      PTS1 was not necessary for targeting. Consistent with these observations we found
      that AO import occurred independent from the C-terminal TPR-domain of HpPex5p,
      known to bind PTS1 peptides. Synthesis of the N-terminal domain (amino acids 1
      272) of HpPex5p in pex5 cells restored AO import, whereas other PTS1 proteins
      were mislocalized to the cytosol. These data indicate that AO is imported via a
      novel HpPex5p-dependent protein translocation pathway, which does not require the
      PTS1 of AO and the C-terminal TPR domains of HpPex5p, but involves FAD binding
      and the N-terminus of HpPex5p.

PMID- 14699076
TI  - Two motifs target Batten disease protein CLN3 to lysosomes in transfected
      nonneuronal and neuronal cells.
AB  - Batten disease is a neurodegenerative disorder resulting from mutations in CLN3,
      a polytopic membrane protein, whose predominant intracellular destination in
      nonneuronal cells is the lysosome. The topology of CLN3 protein, its lysosomal
      targeting mechanism, and the development of Batten disease are poorly understood.
      We provide experimental evidence that both the N and C termini and one large loop
      domain of CLN3 face the cytoplasm. We have identified two lysosomal targeting
      motifs that mediate the sorting of CLN3 in transfected nonneuronal and neuronal
      cells: an unconventional motif in the long C-terminal cytosolic tail consisting
      of a methionine and a glycine separated by nine amino acids [M(X)9G], and a more
      conventional dileucine motif, located in the large cytosolic loop domain and
      preceded by an acidic patch. Each motif on its own was sufficient to mediate
      lysosomal targeting, but optimal efficiency required both. Interestingly, in
      primary neurons, CLN3 was prominently seen both in lysosomes in the cell body and
      in endosomes, containing early endosomal antigen-1 along neuronal processes.
      Because there are few lysosomes in axons and peripheral parts of dendrites, the
      presence of CLN3 in endosomes of neurons may be functionally important. Endosomal
      association of the protein was independent of the two lysosomal targeting motifs.

PMID- 14699077
TI  - Ca2+/calmodulin modulates TRPV1 activation by capsaicin.
AB  - TRPV1 ion channels mediate the response to painful heat, extracellular acidosis,
      and capsaicin, the pungent extract from plants in the Capsicum family (hot chili
      peppers) (Szallasi, A., and P.M. Blumberg. 1999. Pharmacol. Rev. 51:159-212;
      Caterina, M.J., and D. Julius. 2001. Annu. Rev. Neurosci. 24:487-517). The
      convergence of these stimuli on TRPV1 channels expressed in peripheral sensory
      nerves underlies the common perceptual experience of pain due to hot
      temperatures, tissue damage and exposure to capsaicin. TRPV1 channels are
      nonselective cation channels (Caterina, M.J., M.A. Schumacher, M. Tominaga, T.A.
      Rosen, J.D. Levine, and D. Julius. 1997. Nature. 389:816-824). When activated,
      they produce depolarization through the influx of Na+, but their high Ca2+
      permeability is also important for mediating the response to pain. In particular,
      Ca2+ influx is thought to be required for the desensitization to painful
      sensations over time (Cholewinski, A., G.M. Burgess, and S. Bevan. 1993.
      Neuroscience. 55:1015-1023; Koplas, P.A., R.L. Rosenberg, and G.S. Oxford. 1997.
      J. Neurosci. 17:3525-3537). Here we show that in inside-out excised patches from
      TRPV1 expressed in Xenopus oocytes and HEK 293 cells, Ca2+/calmodulin decreased
      the capsaicin-activated current. This inhibition was not mimicked by Mg2+,
      reflected a decrease in open probability, and was slowly reversible. Furthermore,
      increasing the calmodulin concentration in our patches by coexpression of wild
      type calmodulin with TRPV1 produced inhibition by Ca2+ alone. In contrast,
      patches excised from cells coexpressing TRPV1 with a mutant calmodulin did not
      respond to Ca2+. Using an in vitro calmodulin-binding assay, we found that TRPV1
      in oocyte lysates bound calmodulin, although in a Ca2+-independent manner.
      Experiments with GST-fusion proteins corresponding to regions of the channel NH2
      terminal domain demonstrated that a stretch of approximately 30 amino acids
      adjacent to the first ankyrin repeat bound calmodulin in a Ca2+-dependent manner.
      The physiological response to pain involves an influx of Ca2+ through TRPV1. Our
      results indicate that this Ca2+ influx may feed back on the channels, inhibiting
      their gating. This type of feedback inhibition could play a role in the
      desensitization produced by capsaicin.

PMID- 14699078
TI  - In intact mammalian photoreceptors, Ca2+-dependent modulation of cGMP-gated ion
      channels is detectable in cones but not in rods.
AB  - In the mammalian retina, cone photoreceptors efficiently adapt to changing
      background light intensity and, therefore, are able to signal small differences
      in luminance between objects and backgrounds, even when the absolute intensity of
      the background changes over five to six orders of magnitude. Mammalian rod
      photoreceptors, in contrast, adapt very little and only at intensities that
      nearly saturate the amplitude of their photoresponse. In search of a molecular
      explanation for this observation we assessed Ca2+-dependent modulation of ligand
      sensitivity in cyclic GMP-gated (CNG) ion channels of intact mammalian rods and
      cones. Solitary photoreceptors were isolated by gentle proteolysis of ground
      squirrel retina. Rods and cones were distinguished by whether or not their outer
      segments bind PNA lectin. We measured membrane currents under voltage-clamp in
      photoreceptors loaded with Diazo-2, a caged Ca2+ chelator, and fixed
      concentrations of 8Br-cGMP. At 600 nM free cytoplasmic Ca2+ the midpoint of the
      cone CNG channels sensitivity to 8BrcGMP, 8BrcGMPK1/2, is approximately 2.3
      microM. The ligand sensitivity is less in rod than in cone channels. Instantly
      decreasing cytoplasmic Ca2+ to <30 nM activates a large inward membrane current
      in cones, but not in rods. Current activation arises from a Ca2+ -dependent
      modulation of cone CNG channels, presumably because of an increase in their
      affinity to the cyclic nucleotide. The time course of current activation is
      temperature dependent; it is well described by a single exponential process of
      approximately 480 ms time constant at 20-21 degrees C and 138 ms at 32 degrees C.
      The absence of detectable Ca2+-dependent CNG current modulation in intact rods,
      in view of the known channel modulation by calmodulin in-vitro, affirms the
      modulation in intact rods may only occur at low Ca2+ concentrations, those
      expected at intensities that nearly saturate the rod photoresponse. The
      correspondence between Ca2+ dependence of CNG modulation and the ability to light
      adapt suggest these events are correlated in photoreceptors.

PMID- 14699079
TI  - Sensitivity of volume-regulated anion current to cholesterol structural
      analogues.
AB  - Depletion of membrane cholesterol and substitution of endogenous cholesterol with
      its structural analogues was used to analyze the mechanism by which cholesterol
      regulates volume-regulated anion current (VRAC) in endothelial cells. Depletion
      of membrane cholesterol enhanced the development of VRAC activated in a swelling
      independent way by dialyzing the cells either with GTPgammaS or with low ionic
      strength solution. Using MbetaCD-sterol complexes, 50-80% of endogenous
      cholesterol was substituted with a specific analogue, as verified by gas-liquid
      chromatography. The effects of cholesterol depletion were reversed by the
      substitution of endogenous cholesterol with its chiral analogue, epicholesterol,
      or with a plant sterol, beta-sitosterol, two analogues that mimic the effect of
      cholesterol on the physical properties of the membrane bilayer. Alternatively,
      when cholesterol was substituted with coprostanol that has only minimal effect on
      the membrane physical properties it resulted in VRAC enhancement, similar to
      cholesterol depletion. In summary, our data show that these channels do not
      discriminate between the two chiral analogues of cholesterol, as well as between
      the two cholesterols and beta-sitosterol, but discriminate between cholesterol
      and coprostanol. These observations suggest that endothelial VRAC is regulated by
      the physical properties of the membrane.

PMID- 14699080
TI  - Impaired development of CD4+ CD25+ regulatory T cells in the absence of STAT1:
      increased susceptibility to autoimmune disease.
AB  - Type I and II interferons (IFNs) exert opposing effects on the progression of
      multiple sclerosis, even though both IFNs use the signal transducer and activator
      of transcription 1 (STAT1) as a signaling mediator. Here we report that STAT1
      deficient mice expressing a transgenic T cell receptor against myelin basic
      protein spontaneously develop experimental autoimmune encephalomyelitis with
      dramatically increased frequency. The heightened susceptibility to this
      autoimmune disease appears to be triggered by a reduced number as well as a
      functional impairment of the CD4+ CD25+ regulatory T cells in STAT1-deficient
      animals. Adoptive transfer of wild-type regulatory T cells into STAT1-deficient
      hosts is sufficient to prevent the development of autoimmune disease. These
      results demonstrate an essential role of STAT1 in the maintenance of
      immunological self-tolerance.

PMID- 14699081
TI  - BH3-only protein Noxa is a mediator of hypoxic cell death induced by hypoxia
      inducible factor 1alpha.
AB  - Hypoxia is a common cause of cell death and is implicated in many disease
      processes including stroke and chronic degenerative disorders. In response to
      hypoxia, cells express a variety of genes, which allow adaptation to altered
      metabolic demands, decreased oxygen demands, and the removal of irreversibly
      damaged cells. Using polymerase chain reaction-based suppression subtractive
      hybridization to find genes that are differentially expressed in hypoxia, we
      identified the BH3-only Bcl-2 family protein Noxa. Noxa is a candidate molecule
      mediating p53-induced apoptosis. We show that Noxa promoter responds directly to
      hypoxia via hypoxia-inducible factor (HIF)-1alpha. Suppression of Noxa expression
      by antisense oligonucleotides rescued cells from hypoxia-induced cell death and
      decreased infarction volumes in an animal model of ischemia. Further, we show
      that reactive oxygen species and resultant cytochrome c release participate in
      Noxa-mediated hypoxic cell death. Altogether, our results show that Noxa is
      induced by HIF-1alpha and mediates hypoxic cell death.

PMID- 14699082
TI  - Toll-like receptors induce a phagocytic gene program through p38.
AB  - Toll-like receptor (TLR) signaling and phagocytosis are hallmarks of macrophage
      mediated innate immune responses to bacterial infection. However, the
      relationship between these two processes is not well established. Our data
      indicate that TLR ligands specifically promote bacterial phagocytosis, in both
      murine and human cells, through induction of a phagocytic gene program.
      Importantly, TLR-induced phagocytosis of bacteria was found to be reliant on
      myeloid differentiation factor 88-dependent signaling through interleukin-1
      receptor-associated kinase-4 and p38 leading to the up-regulation of scavenger
      receptors. Interestingly, individual TLRs promote phagocytosis to varying degrees
      with TLR9 being the strongest and TLR3 being the weakest inducer of this process.
      We also demonstrate that TLR ligands not only amplify the percentage of
      phagocytes uptaking Escherichia coli, but also increase the number of bacteria
      phagocytosed by individual macrophages. Taken together, our data describe an
      evolutionarily conserved mechanism by which TLRs can specifically promote
      phagocytic clearance of bacteria during infection.

PMID- 14699083
TI  - Surrogate light chain expressing human peripheral B cells produce self-reactive
      antibodies.
AB  - Human B cells that coexpress surrogate and conventional light chains (V-preB+L+)
      show an unusual heavy and light chain antibody repertoire that display evidence
      of receptor editing. However, it is unclear whether V-preB+L+ B cells have been
      silenced by receptor editing or still express autoreactive antibodies. Here we
      report that 68% of the antibodies expressed by V-preB+L+ B cells are
      autoreactive. A majority of these autoantibodies are true antinuclear antibodies
      (ANA), and 50% of the ANAs are also reactive with a diverse group of antigens
      that include dsDNA, ssDNA, immunoglobulin, insulin, and bacterial
      lipopolysaccharide. Such antibodies are rarely encountered among conventional B
      cells. We conclude that V-preB+L+ B cells are a unique subset of normal
      circulating human B cells that escape central tolerance mechanisms and express
      self-reactive antibodies including potentially harmful ANAs.

PMID- 14699084
TI  - Cytomegalovirus misleads its host by priming of CD8 T cells specific for an
      epitope not presented in infected tissues.
AB  - Cytomegaloviruses (CMVs) code for several proteins that inhibit the presentation
      of antigenic peptides to CD8 T cells. Although the molecular mechanisms of CMV
      interference with the major histocompatibility complex class I pathway are long
      understood, surprisingly little evidence exists to support a role in vivo. Here
      we document the first example of the presentation of an antigenic peptide being
      blocked by a CMV immune evasion protein in organs relevant to CMV disease.
      Although this Db-restricted peptide, which is derived from the antiapoptotic
      protein M45 of murine CMV (mCMV), is classified as an immunodominant peptide
      based on response magnitude and long-term memory, adoptive transfer of M45
      epitope-specific CD8 T cells did not protect against infection with wild-type
      mCMV. Notably, the same cells protected C57BL/6 mice infected with an mCMV mutant
      in which immune evasion protein m152/gp40 is deleted. These data indicate that
      direct presentation or cross-presentation of an antigenic peptide by professional
      antigen-presenting cells can efficiently prime CD8 T cells that fail in
      protection against CMV organ disease because m152/gp40 prevents presentation of
      this peptide in pathogenetically relevant tissue cells.

PMID- 14699085
TI  - Essential role of survivin, an inhibitor of apoptosis protein, in T cell
      development, maturation, and homeostasis.
AB  - Survivin is an inhibitor of apoptosis protein that also functions during mitosis.
      It is expressed in all common tumors and tissues with proliferating cells,
      including thymus. To examine its role in apoptosis and proliferation, we
      generated two T cell-specific survivin-deficient mouse lines with deletion
      occurring at different developmental stages. Analysis of early deleting survivin
      mice showed arrest at the pre-T cell receptor proliferating checkpoint. Loss of
      survivin at a later stage resulted in normal thymic development, but peripheral T
      cells were immature and significantly reduced in number. In contrast to in vitro
      studies, loss of survivin does not lead to increased apoptosis. However, newborn
      thymocyte homeostatic and mitogen-induced proliferation of survivin-deficient T
      cells were greatly impaired. These data suggest that survivin is not essential
      for T cell apoptosis but is crucial for T cell maturation and proliferation, and
      survivin-mediated homeostatic expansion is an important physiological process of
      T cell development.

PMID- 14699086
TI  - Stress-induced transcription of satellite III repeats.
AB  - Exposure of mammalian cells to stress induces the activation of heat shock
      transcription factor 1 (HSF1) and the subsequent transcription of heat shock
      genes. Activation of the heat shock response also correlates with a rapid
      relocalization of HSF1 within a few nuclear structures termed nuclear stress
      granules. These stress-induced structures, which form primarily on the 9q12
      region in humans through direct binding of HSF1 to satellite III repeats, do not
      colocalize with transcription sites of known hsp genes. In this paper, we show
      that nuclear stress granules correspond to RNA polymerase II transcription
      factories where satellite III repeats are transcribed into large and stable RNAs
      that remain associated with the 9q12 region, even throughout mitosis. This work
      not only reveals the existence of a new major heat-induced transcript in human
      cells that may play a role in chromatin structure, but also provides evidence for
      a transcriptional activity within a locus considered so far as heterochromatic
      and silent.

PMID- 14699087
TI  - Ca2+-dependent redox modulation of SERCA 2b by ERp57.
AB  - We demonstrated previously that calreticulin (CRT) interacts with the lumenal
      COOH-terminal sequence of sarco endoplasmic reticulum (ER) calcium ATPase (SERCA)
      2b to inhibit Ca2+ oscillations. Work from other laboratories demonstrated that
      CRT also interacts with the ER oxidoreductase, ER protein 57 (also known as ER
      60, GRP58; ERp57) during folding of nascent glycoproteins. In this paper, we
      demonstrate that ERp57 overexpression reduces the frequency of Ca2+ oscillations
      enhanced by SERCA 2b. In contrast, overexpression of SERCA 2b mutants defective
      in cysteines located in intralumenal loop 4 (L4) increase Ca2+ oscillation
      frequency. In vitro, we demonstrate a Ca2+-dependent and -specific interaction
      between ERp57 and L4. Interestingly, ERp57 does not affect the activity of SERCA
      2a or SERCA 2b mutants lacking the CRT binding site. Overexpression of CRT
      domains that disrupt the interaction of CRT with ERp57 behave as dominant
      negatives in the Ca2+ oscillation assay. Our results suggest that ERp57 modulates
      the redox state of ER facing thiols in SERCA 2b in a Ca2+-dependent manner,
      providing dynamic control of ER Ca2+ homeostasis.

PMID- 14699088
TI  - i-SNAREs: inhibitory SNAREs that fine-tune the specificity of membrane fusion.
AB  - A new functional class of SNAREs, designated inhibitory SNAREs (i-SNAREs), is
      described here. An i-SNARE inhibits fusion by substituting for or binding to a
      subunit of a fusogenic SNAREpin to form a nonfusogenic complex. Golgi-localized
      SNAREs were tested for i-SNARE activity by adding them as a fifth SNARE together
      with four other SNAREs that mediate Golgi fusion reactions. A striking pattern
      emerges in which certain subunits of the cis-Golgi SNAREpin function as i-SNAREs
      that inhibit fusion mediated by the trans-Golgi SNAREpin, and vice versa.
      Although the opposing distributions of the cis- and trans-Golgi SNAREs themselves
      could provide for a countercurrent fusion pattern in the Golgi stack, the
      gradients involved would be strongly sharpened by the complementary
      countercurrent distributions of the i-SNAREs.

PMID- 14699089
TI  - AHNAK interaction with the annexin 2/S100A10 complex regulates cell membrane
      cytoarchitecture.
AB  - Remodelling of the plasma membrane cytoarchitecture is crucial for the regulation
      of epithelial cell adhesion and permeability. In Madin-Darby canine kidney cells,
      the protein AHNAK relocates from the cytosol to the cytosolic surface of the
      plasma membrane during the formation of cell-cell contacts and the development of
      epithelial polarity. This targeting is reversible and regulated by Ca(2+)
      dependent cell-cell adhesion. At the plasma membrane, AHNAK associates as a
      multimeric complex with actin and the annexin 2/S100A10 complex. The S100A10
      subunit serves to mediate the interaction between annexin 2 and the COOH-terminal
      regulatory domain of AHNAK. Down-regulation of both annexin 2 and S100A10 using
      an annexin 2-specific small interfering RNA inhibits the association of AHNAK
      with plasma membrane. In Madin-Darby canine kidney cells, down-regulation of
      AHNAK using AHNAK-specific small interfering RNA prevents cortical actin
      cytoskeleton reorganization required to support cell height. We propose that the
      interaction of AHNAK with the annexin 2/S100A10 regulates cortical actin
      cytoskeleton organization and cell membrane cytoarchitecture.

PMID- 14699090
TI  - The Omp85 family of proteins is essential for outer membrane biogenesis in
      mitochondria and bacteria.
AB  - Integral proteins in the outer membrane of mitochondria control all aspects of
      organelle biogenesis, being required for protein import, mitochondrial fission,
      and, in metazoans, mitochondrial aspects of programmed cell death. How these
      integral proteins are assembled in the outer membrane had been unclear. In
      bacteria, Omp85 is an essential component of the protein insertion machinery, and
      we show that members of the Omp85 protein family are also found in eukaryotes
      ranging from plants to humans. In eukaryotes, Omp85 is present in the
      mitochondrial outer membrane. The gene encoding Omp85 is essential for cell
      viability in yeast, and conditional omp85 mutants have defects that arise from
      compromised insertion of integral proteins like voltage-dependent anion channel
      (VDAC) and components of the translocase in the outer membrane of mitochondria
      (TOM) complex into the mitochondrial outer membrane.

PMID- 14699091
TI  - Assembly, maturation, and turnover of K(ATP) channel subunits.
AB  - ATP-sensitive K(+), or K(ATP), channels are comprised of K(IR)6.x and
      sulfonylurea receptor (SUR) subunits that assemble as octamers, (K(IR)/SUR)(4).
      The assembly pathway is unknown. Pulse-labeling studies show that when K(IR)6.2
      is expressed individually, its turnover is biphasic; approximately 60% is lost
      with t((1/2)) approximately 36 min. The remainder converts to a long-lived
      species (t((1/2)) approximately 26 h) with an estimated half-time of 1.2 h.
      Expressed alone, SUR1 has a long half-life, approximately 25.5 h. When K(IR)6.2
      and SUR1 are co-expressed, they associate rapidly and the fast degradation of
      K(IR)6.2 is eliminated. Based on changes in the glycosylation state of SUR1, the
      half-time for the maturation of K(ATP) channels, including completion of
      assembly, transit to the Golgi, and glycosylation, is approximately 2.2 h.
      Estimation of the turnover rates of mature, fully glycosylated SUR1 associated
      with K(IR)6.2 and of K(IR)6.2 associated with Myc-tagged SUR1 gave similar values
      for the half-life of K(ATP) channels, a mean value of approximately 7.3 h. K(ATP)
      channel subunits in INS-1 beta-cells displayed qualitatively similar kinetics.
      The results imply the octameric channels are stable. Two mutations, K(IR)6.2 W91R
      and SUR1 DeltaF1388, identified in patients with the severe form of familial
      hyperinsulinism, profoundly alter the rate of K(IR)6.2 and SUR1 turnover,
      respectively. Both mutant subunits associate with their respective partners but
      dissociate freely and degrade rapidly. The data support models of channel
      formation in which K(IR)6.2-SUR1 heteromers assemble functional channels and are
      inconsistent with models where SUR1 can only assemble with K(IR)6.2 tetramers.

PMID- 14699092
TI  - Purification and characterization of a barley aleurone abscisic acid-binding
      protein.
AB  - A protein designated ABAP1 and encoded by a novel gene (GenBank accession number
      AF127388) was purified and shown to specifically bind abscisic acid (ABA). ABAP1
      protein is a 472-amino acid polypeptide containing a WW protein interaction
      domain and is induced by ABA in barley aleurone layers. Polyclonal antiidiotypic
      antibodies (AB2) cross-reacted with purified ABAP1 and with a corresponding 52
      kDa protein associated with membrane fractions of ABA-treated barley aleurones.
      ABAP1 genes were detected in diverse monocot and dicot species, including wheat,
      tobacco, alfalfa, garden pea, and oilseed rape. The recombinant ABAP1 protein
      optimally bound (3)H-(+)-ABA at neutral pH. Denatured ABAP1 protein did not bind
      (3)H-(+)-ABA, nor did bovine serum albumin. The maximum specific binding as shown
      by Scatchard plot analysis was 0.8 mol of ABA mol(-1) protein with a linear
      function of r(2) = 0.94, an indication of one ABA-binding site with a
      dissociation constant (K(d)) of 28 x 10(-9) m. ABA binding in aleurone plasma
      membranes showed a maximum binding capacity of 330 nmol of ABA g(-1) protein with
      a K(d) of 26.5 x 10(-9) m. The similarities in the dissociation constants for ABA
      binding of the recombinant protein and that of the plasma membranes suggest that
      the protein within the plasma membrane fraction is the native form of ABAP1. The
      stereospecificity of ABAP1 was established by the incapability of ABA analogs and
      metabolites, including (-)-ABA, trans-ABA, phaseic acid, dihydrophaseic acid, and
      (+)-abscisic acid-glucose ester, to displace (3)H-(+)-ABA bound to ABAP1.
      However, two ABA precursors, (+)-ABA aldehyde and (+)-ABA alcohol, were able to
      displace (3)H-(+)-ABA, an indication that the structural requirement of ABAP1 at
      the C-1 position is not strict. Our data show that ABAP1 exerts high binding
      affinity for ABA. The interaction is reversible, follows saturation kinetics, and
      has stereospecificity, thus meeting the criteria for an ABA-binding protein.

PMID- 14699093
TI  - Protease nexin-1 inhibits plasminogen activation-induced apoptosis of adherent
      cells.
AB  - Degradation of adhesive glycoproteins by plasmin is implicated in cell migration.
      In this study, we further explored the role of plasminogen activation in cell
      adhesion and survival and show that uncontrolled plasminogen activation at the
      cell surface may induce cell detachment and apoptosis. We hypothesized that this
      process could be prevented in adherent cells by expression of protease nexin-1, a
      potent serpin able to inhibit thrombin, plasmin, and plasminogen activators.
      Using two- and three-dimensional culture systems, we demonstrate that Chinese
      hamster ovary fibroblasts constitutively express tissue-type plasminogen
      activator and efficiently activate exogenously added plasminogen in a specific
      and saturable manner (K(m) = 46 nm). The formation of plasmin results in
      proteolysis of fibronectin and laminin, which is followed by cell detachment and
      apoptosis. Protease nexin-1 expressed by transfected cells significantly
      inhibited the activity of plasmin and tissue-type plasminogen activator via the
      formation of inhibitory complexes and prevented cell detachment and apoptosis. In
      conclusion, protease nexin-1 may be an important anti-apoptotic factor for
      adherent cells. This cell model could be a useful tool to evaluate therapeutic
      agents such as serpins in vascular pathologies involving pericellular protease
      protease inhibitor imbalance.

PMID- 14699094
TI  - Chondroitin sulfate/dermatan sulfate hybrid chains from embryonic pig brain,
      which contain a higher proportion of L-iduronic acid than those from adult pig
      brain, exhibit neuritogenic and growth factor binding activities.
AB  - We have shown that over-sulfated chondroitin sulfate/dermatan sulfate (CS/DS)
      chains from various marine organisms exhibit growth factor binding activities and
      neurite outgrowth-promoting activities in embryonic mouse hippocampal neurons in
      vitro. In this study we demonstrated that CS/DS hybrid chains purified from
      embryonic pig brain displayed marked neuritogenic activity and growth factor
      binding activities toward fibroblast growth factor 2 (FGF2), FGF10, FGF18,
      pleiotrophin, and midkine, all of which exhibit neuroregulatory activities in the
      brain. In contrast, the CS/DS preparation from adult pig brain showed
      considerably less activity to bind these growth factors and no neuritogenic
      activity. Structural analysis indicated that the average size of the CS/DS chains
      was similar (40 kDa) between these two preparations, but the disaccharide
      compositions differed considerably, with a significant proportion of l-iduronic
      acid (IdoUA)-containing disaccharides (8 approximately 9%) in the CS/DS chains
      from embryos but not in those from adults (<1%). Interestingly, both neurite
      outgrowth-promoting activity and growth factor binding activities of the CS/DS
      chains from embryos were abolished by digestion not only with chondroitinase ABC
      but also with chondroitinase B, suggesting that the IdoUA-containing motifs are
      essential for these activities. These findings imply that the temporal expression
      of CS/DS hybrid structures containing both GlcUA and IdoUA and binding activities
      toward various growth factors play important roles in neurogenesis in the early
      stages of the development of the brain.

PMID- 14699095
TI  - The lipid body protein, PpoA, coordinates sexual and asexual sporulation in
      Aspergillus nidulans.
AB  - The coexistence of sexual and asexual reproductive cycles within the same
      individual is a striking phenomenon in numerous fungi. In the fungus Aspergillus
      nidulans (teleomorph: Emericella nidulans) endogenous oxylipins, called psi
      factor, serve as hormone-like signals that modulate the timing and balance
      between sexual and asexual spore development. Here, we report the identification
      of A. nidulans ppoA, encoding a putative fatty acid dioxygenase, involved in the
      biosynthesis of the linoleic acid derived oxylipin psiBalpha. PpoA is required
      for balancing anamorph and teleomorph development. Deletion of ppoA significantly
      reduced the level of psiBalpha and increased the ratio of asexual to sexual spore
      numbers 4-fold. In contrast, forced expression of ppoA resulted in elevated
      levels of psiBalpha and decreased the ratio of asexual to sexual spore numbers 6
      fold. ppoA expression is mediated by two developmental regulators, VeA and the
      COP9 signalosome, such that ppoA transcript levels are correlated with the
      initiation of asexual and sexual fruiting body formation. PpoA localizes in lipid
      bodies in these tissues. These data support an important role for oxylipins in
      integrating mitotic and meiotic spore development.

PMID- 14699096
TI  - Requirements for West Nile virus (-)- and (+)-strand subgenomic RNA synthesis in
      vitro by the viral RNA-dependent RNA polymerase expressed in Escherichia coli.
AB  - RNA-dependent RNA polymerases (RdRPs) of the Flaviviridae family catalyze
      replication of positive (+)- strand viral RNA through synthesis of minus (-)-and
      progeny (+)-strand RNAs. West Nile virus (WNV), a mosquito-borne member, is a
      rapidly re-emerging human pathogen in the United States since its first outbreak
      in 1999. To study the replication of the WNV RNA in vitro, an assay is described
      here that utilizes the WNV RdRP and subgenomic (-)- and (+)-strand template RNAs
      containing 5'- and 3'-terminal regions (TR) with the conserved sequence elements.
      Our results show that both 5'- and 3'-TRs of the (+)-strand RNA template
      including the wild type cyclization (CYC) motifs are important for RNA synthesis.
      However, the 3'-TR of the (-)-strand RNA template alone is sufficient for RNA
      synthesis. Mutational analysis of the CYC motifs revealed that the (+)-strand 5'
      CYC motif is critical for (-)-strand RNA synthesis but neither the (-)-strand 5'-
      nor 3'-CYC motif is important for the (+)-strand RNA synthesis. Moreover, the 5'
      cap inhibits the (-)-strand RNA synthesis from the 3' fold-back structure of (+)
      strand RNA template without affecting the de novo synthesis of RNA. These results
      support a model that "cyclization" of the viral RNA play a role for (-)-strand
      RNA synthesis but not for (+)-strand RNA synthesis.

PMID- 14699097
TI  - Prevention of ginsenoside-induced desensitization of Ca2+-activated Cl- current
      by microinjection of inositol hexakisphosphate in Xenopus laevis oocytes:
      involvement of GRK2 and beta-arrestin I.
AB  - We demonstrated that ginsenosides, the active ingredient of Panax ginseng,
      enhance endogenous Ca(2+)-activated Cl(-) currents via Galpha(q/11)-phospholipase
      C-beta3 pathway in Xenopus laevis oocytes. Moreover, prolonged treatment of
      ginsenosides induced Cl(-) channel desensitization. However, the molecular
      mechanisms involved in ginsenoside-induced Cl(-) channel desensitization have not
      yet been determined precisely. To provide answers to these questions, we
      investigated the changes in ginsenoside-induced Cl(-) channel desensitization
      after intraoocyte injection of inositol hexakisphosphate (InsP(6)), which is
      known to bind beta-arrestins and interfere with beta-arrestin-induced receptor
      down-regulation, and cRNAs coding beta-arrestin I/II and G-protein receptor
      kinase 2 (GRK2), which is known to phosphorylate G protein-coupled receptors and
      attenuate agonist stimulations. When control oocytes were stimulated with
      ginsenosides, the second, third, and fourth responses to ginsenosides were 69.6
      +/- 4.1, 9.2 +/- 2.3, and 2.6 +/- 2.2% of the first responses, respectively.
      Preintraoocyte injection of InsP(6) before ginsenoside treatment restored
      ginsenoside effect to initial response levels in a concentration-, time-, and
      structurally specific manner, in that inositol hexasulfate had no effect. The
      EC(50) was 13.9 +/- 8.7 microM. Injection of cRNA coding beta-arrestin I but not
      beta-arrestin II blocked InsP(6) effect on prevention of ginsenoside-induced Cl(
      ) channel desensitization. Injection of cRNA coding GRK2 abolished ginsenoside
      effect enhancing Cl(-) current. However, the GRK2-caused loss of ginsenoside
      effect on Cl(-) current was prevented by coinjection of GRK2 with GRK2-K220R, a
      dominant-negative mutant of GRK. These results indicate that ginsenoside-induced
      Cl(-) channel desensitization is mediated via activation of GRK2 and beta
      arrestin I.

PMID- 14699098
TI  - Lectin-deficient calnexin is capable of binding class I histocompatibility
      molecules in vivo and preventing their degradation.
AB  - Calnexin is a membrane-bound lectin of the endoplasmic reticulum (ER) that binds
      transiently to newly synthesized glycoproteins. By interacting with
      oligosaccharides of the form Glc(1)Man(9)GlcNAc(2), calnexin enhances the folding
      of glycoprotein substrates, retains misfolded variants in the ER, and in some
      cases participates in their degradation. Calnexin has also been shown to bind
      polypeptides in vivo that do not possess a glycan of this form and to function in
      vitro as a molecular chaperone for nonglycosylated proteins. To test the relative
      importance of the lectin site compared with the polypeptide-binding site, we have
      generated six calnexin mutants defective in oligosaccharide binding using site
      directed mutagenesis. Expressed as glutathione S-transferase fusions, these
      mutants were still capable of binding ERp57, a thiol oxidoreductase, and
      preventing the aggregation of a nonglycosylated substrate, citrate synthase. They
      were, however, unable to bind Glc(1) Man(9)GlcNAc(2) oligosaccharide and were
      compromised in preventing the aggregation of the monoglucosylated substrate jack
      bean alpha-mannosidase. Two of these mutants were then engineered into full
      length calnexin for heterologous expression in Drosophila cells along with the
      murine class I histocompatibility molecules K(b) and D(b) as model glycoproteins.
      In this system, lectin site-defective calnexin was able to replace wild type
      calnexin in forming a complex with K(b) and D(b) heavy chains and preventing
      their degradation. Thus, at least for class I molecules, the lectin site of
      calnexin is dispensable for some of its chaperone functions.

PMID- 14699099
TI  - The eag potassium channel binds and locally activates calcium/calmodulin
      dependent protein kinase II.
AB  - Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the
      regulation of neuronal excitability in many systems. Recent studies suggest that
      local regulation of membrane potential can have important computational
      consequences for neuronal function. In Drosophila, CaMKII regulates the eag
      potassium channel, but if and how this regulation was spatially restricted was
      unknown. Using coimmunoprecipitation from head extracts and in vitro binding
      assays, we show that CaMKII and Eag form a stable complex and that association
      with Eag activates CaMKII independently of CaM and autophosphorylation.
      Ca(2+)/CaM is necessary to initiate binding of CaMKII to Eag but not to sustain
      association because binding persists when CaM is removed. The Eag CaMKII-binding
      domain has homology to the CaMKII autoregulatory region, and the constitutively
      active CaMKII mutant, T287D, binds Eag Ca(2+)-independently in vitro and in vivo.
      These results favor a model in which the CaMKII-binding domain of Eag displaces
      the CaMKII autoinhibitory region. Displacement results in autophosphorylation
      independent activation of CaMKII which persists even when Ca(2+) levels have gone
      down. Activity-dependent binding to this potassium channel substrate allows
      CaMKII to remain locally active even when Ca(2+) levels have dropped, providing a
      novel mechanism by which CaMKII can regulate excitability locally over long time
      scales.

PMID- 14699100
TI  - Identification of free radicals on hemoglobin from its self-peroxidation using
      mass spectrometry and immuno-spin trapping: observation of a histidinyl radical.
AB  - In an effort to understand the mechanism of radical formation on heme proteins,
      the formation of radicals on hemoglobin was initiated by reaction with hydrogen
      peroxide in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide
      (DMPO). The DMPO nitrone adducts were analyzed by mass spectrometry (MS) and
      immuno-spin trapping. The spin-trapped protein adducts were then subjected to
      tryptic digestion and MS analyses. When hemoglobin was reacted with hydrogen
      peroxide (H(2)O(2)) in the presence of DMPO, a DMPO nitrone adduct could be
      detected by immuno-spin trapping. To verify that DMPO adducts of the protein free
      radicals had been formed, the reaction mixtures were analyzed by flow injection
      electrospray ionization mass spectrometry (ESI/MS). The ESI mass spectrum of the
      hemoglobin/H(2)O(2)/DMPO sample shows one adduct each on both the alpha chain and
      the beta chain of hemoglobin which corresponds in mass to the addition of one
      DMPO molecule. The nature of the radicals formed on hemoglobin was explored using
      proteolysis techniques followed by liquid chromatography/mass spectrometry
      (LC/MS) and tandem mass spectrometry (MS/MS) analyses. The following sites of
      DMPO addition were identified on hemoglobin: Cys-93 of the beta chain, and Tyr
      42, Tyr-24, and His-20 of the alpha chain. Because of the pi-pi interaction of
      Tyr-24 and His-20, the unpaired electron is apparently delocalized on both the
      tyrosine and histidine residue (pi-pi stacked pair radical).

PMID- 14699101
TI  - Physicochemical features of the HERG channel drug binding site.
AB  - Blockade of hERG K(+) channels in the heart is an unintentional side effect of
      many drugs and can induce cardiac arrhythmia and sudden death. It has become
      common practice in the past few years to screen compounds for hERG channel
      activity early during the drug discovery process. Understanding the molecular
      basis of drug binding to hERG is crucial for the rational design of medications
      devoid of this activity. We previously identified 2 aromatic residues, Tyr-652
      and Phe-656, located in the S6 domain of hERG, as critical sites of interaction
      with structurally diverse drugs. Here, Tyr-652 and Phe-656 were systematically
      mutated to different residues to determine how the physicochemical properties of
      the amino acid side group affected channel block by cisapride, terfenadine, and
      MK-499. The potency for block by all three drugs was well correlated with
      measures of hydrophobicity, especially the two-dimensional approximation of the
      van der Waals hydrophobic surface area of the side chain of residue 656. For
      residue 652, an aromatic side group was essential for high affinity block,
      suggesting the importance of a cation-pi interaction between Tyr-652 and the
      basic tertiary nitrogen of these drugs. hERG also lacks a Pro-Val-Pro motif
      common to the S6 domain of most other voltage-gated K(+) channels. Introduction
      of Pro-Val-Pro into hERG reduced sensitivity to drugs but also altered channel
      gating. Together, these findings assign specific residues to receptor fields
      predicted by pharmacophore models of hERG channel blockers and provide a refined
      molecular understanding of the drug binding site.

PMID- 14699102
TI  - Termination of protease-activated receptor-1 signaling by beta-arrestins is
      independent of receptor phosphorylation.
AB  - Protease-activated receptor 1 (PAR1), a G protein-coupled receptor (GPCR) for
      thrombin, is the prototypic member of a family of protease-activated receptors.
      PAR1 is irreversibly proteolytically activated; thus, the magnitude and duration
      of thrombin cellular responses are determined primarily by mechanisms responsible
      for termination of receptor signaling. Both phosphorylation and beta-arrestins
      contribute to rapid desensitization of PAR1 signaling. However, the relative
      contribution of each of these pathways to the termination of PAR1 signaling is
      not known. Co-expression of PAR1 with beta-arrestin 1 (betaarr1) in COS-7 cells
      resulted in a marked inhibition of PAR1 signaling, whereas beta-arrestin 2
      (betaarr2) was essentially inactive. Strikingly, signaling by a PAR1 cytoplasmic
      tail mutant defective in agonist-induced phosphorylation was also attenuated more
      effectively by betaarr1 compared with betaarr2. In contrast, both beta-arrestin
      isoforms were equally effective at desensitizing the substance P receptor, a
      classic reversibly activated GPCR. PAR1 coimmunoprecipitated betaarr1 in an
      agonist-dependent manner, whereas betaarr2 association was virtually
      undetectable. Remarkably, betaarr1 also interacted with phosphorylation defective
      PAR1 mutant, whereas betaarr2 did not. Moreover, constitutively active beta
      arrestin mutants, betaarr1 R169E and betaarr2 R170E, that bind to activated
      receptor independent of phosphorylation failed to enhance either wild type or
      mutant PAR1 desensitization compared with normal versions of these proteins. In
      contrast, beta-arrestin mutants displayed enhanced activity at desensitizing the
      serotonin 5-hydroxytryptamine(2A) receptor. Taken together, these results suggest
      that, in addition to PAR1 cytoplasmic tail phosphorylation itself, beta-arrestin
      binding independent of phosphorylation promotes desensitization of PAR1
      signaling. These findings reveal a new level of complexity in the regulation of
      protease-activated GPCR signaling.

PMID- 14699104
TI  - The structural GDP/GTP cycle of Rab11 reveals a novel interface involved in the
      dynamics of recycling endosomes.
AB  - The small GTP-binding protein Rab11 is an essential regulator of the dynamics of
      recycling endosomes. Here we report the crystallographic analysis of the GDP/GTP
      cycle of human Rab11a, and a structure-based mutagenesis study that identifies a
      novel mutant phenotype. The crystal structures show that the nucleotide-sensitive
      switch 1 and 2 regions differ from those of other Rab proteins. In Rab11-GDP,
      they contribute to a close packed symmetrical dimer, which may associate to
      membranes in the cell and allow Rab11 to undergo GDP/GTP cycles without recycling
      to the cytosol. The structure of active Rab11 delineates a three-dimensional site
      that includes switch 1 and is separate from the site defined by the
      Rab3/Rabphilin interface. It is proposed to form a novel interface for a Rab11
      partner compatible with the simultaneous binding of another partner at the
      Rabphilin interface. Mutation of Ser(29) to Phe in this epitope resulted in
      morphological modifications of the recycling compartment that are distinct from
      those induced by the classical dominant-negative and constitutively active Rab11
      mutants. Recycling endosomes condensed in the perinuclear region where they
      retained recycling transferrin, and they clustered Rab11- and EEA1-positive
      membranes. Altogether, our study suggests that this mutation impairs a specific
      subset of Rab11 interactions, possibly those involved in cytoskeleton-based
      movements driving the slow recycling pathway.

PMID- 14699103
TI  - Transcription of the vascular endothelial growth factor gene in macrophages is
      regulated by liver X receptors.
AB  - Macrophages are an important source of angiogenic activity in wound healing,
      cancer, and chronic inflammation. Vascular endothelial growth factor (VEGF), a
      cytokine produced by macrophages, is a primary inducer of angiogenesis and
      neovascularization in these contexts. VEGF expression by macrophages is known to
      be stimulated by low oxygen tension as well as by inflammatory signals. In this
      study, we provide evidence that Vegfa gene expression is also regulated by
      activation of liver X receptors (LXRs). VEGF mRNA was induced in response to
      synthetic LXR agonists in murine and human primary macrophages as well as in
      murine adipose tissue in vivo. The effects of LXR ligands on VEGF expression were
      independent of hypoxia-inducible factor HIF-1alpha activation and did not require
      the previously characterized hypoxia response element in the VEGF promoter.
      Rather, LXR/retinoid X receptor heterodimers bound directly to a conserved
      hormone response element (LXRE) in the promoter of the murine and human Vegfa
      genes. Both LXRalpha and LXRbeta transactivated the VEGF promoter in transient
      transfection assays. Finally, we show that induction of VEGF expression by
      inflammatory stimuli was independent of LXRs, because these effects were
      preserved in LXR null macrophages. These observations identify VEGF as an LXR
      target gene and point to a previously unrecognized role for LXRs in vascular
      biology.

PMID- 14699105
TI  - Multiple actions of imperatoxin A on ryanodine receptors: interactions with the
      II-III loop "A" fragment.
AB  - Imperatoxin A is a high affinity activator of ryanodine receptors. The toxin
      contains a positively charged surface structure similar to that of the A fragment
      of skeletal dihydropyridine receptors (peptide A), suggesting that the toxin and
      peptide could bind to a common site on the ryanodine receptor. However, the
      question of a common binding site has not been resolved, and the concentration
      dependence of the actions of the toxin has not been fully explored. We
      characterize two novel high affinity actions of the toxin on the transient gating
      of cardiac and skeletal channels, in addition to the well documented lower
      affinity induction of prolonged substates. Transient activity was (a) enhanced
      with 0.2-10 nm toxin and (b) depressed by >50 nm toxin. The toxin at >/=1 nm
      enhanced Ca(2+) release from SR in a manner consistent with two independent
      activation processes. The effects of the toxin on transient activity, as well as
      the toxin-induced substate, were independent of cytoplasmic Ca(2+) or Mg(2+)
      concentrations or the presence of adenine nucleotide and were seen in
      diisothiocyanostilbene-2',2'-disulfonic acid-modified channels. Peptide A
      activated skeletal and cardiac channels with 100 nm cytoplasmic Ca(2+) and
      competed with Imperatoxin A in the high affinity enhancement of transient channel
      activity and Ca(2+) release from SR. In contrast to transient activity, prolonged
      substate openings induced by the toxin were not altered in the presence of
      peptide A. The results suggest that Imperatoxin A has three independent actions
      on ryanodine receptor channels and competes with peptide A for at least one
      action.

PMID- 14699106
TI  - Role of the transmembrane domain in the stability of TrwB, an integral protein
      involved in bacterial conjugation.
AB  - TrwB is an integral membrane protein encoded by the conjugative plasmid R388.
      TrwB binds ATP and is essential for R388-directed bacterial conjugation. The
      protein consists of a cytosolic domain, which contains an ATP-binding site, and a
      transmembrane domain. The complete protein has been purified in the presence of
      detergents, and in addition, the cytosolic domain has also been isolated in the
      form of a soluble truncated protein, TrwBDeltaN70. The availability of intact and
      truncated forms of the protein provides a convenient system to study the role of
      the transmembrane domain in the stability of TrwB. Protein denaturation was
      achieved by heat, in the presence of guanidinium HCl, or under low salt
      conditions. In all three cases TrwB was significantly more stable than
      TrwBDeltaN70 with other conditions being the same. IR spectroscopy of the native
      and truncated forms revealed significant differences between them. In addition,
      it was found that TrwBDeltaN70 was stabilized in dispersions of non-ionic
      detergent, suggesting the presence of hydrophobic patches on the surface of the
      truncated protein. IR spectroscopy also confirmed the conformational stability
      provided by the detergent. These results suggest that in integral membrane
      proteins consisting of a transmembrane and a cytosolic domain, the transmembrane
      portion may have a role beyond the mere anchoring of the protein to the cell
      membrane. In addition, this study indicates that the truncated soluble parts of
      two-domain membrane proteins may not reflect the physiological conformation of
      their native counterparts.

PMID- 14699107
TI  - Optimum amyloid fibril formation of a peptide fragment suggests the amyloidogenic
      preference of beta2-microglobulin under physiological conditions.
AB  - Beta(2)-microglobulin (beta(2)m) is a major component of amyloid fibrils
      deposited in patients with dialysis-related amyloidosis. Although full-length
      beta(2)m readily forms amyloid fibrils in vitro by seed-dependent extension with
      a maximum at pH 2.5, fibril formation under physiological conditions as detected
      in patients has been difficult to reproduce. A 22-residue K3 peptide of beta(2)m,
      Ser(20)-Lys(41), obtained by digestion with Acromobacter protease I, forms
      amyloid fibrils without seeding. To obtain further insight into the mechanism of
      fibril formation, we studied the pH dependence of fibril formation of the K3
      peptide and its morphology using a ThT fluorescence assay and electron
      microscopy, respectively. K3 peptide formed amyloid fibrils over a wide range of
      pH values with an optimum around pH 7 and contrasted with the pH profile of the
      seed-dependent extension reaction of full-length beta(2)m. This suggests that
      once the rigid native-fold of beta(2)m is unfolded and additional factors
      triggering the nucleation process are provided, full-length beta(2)m discloses an
      intrinsic potential to form amyloid fibrils at neutral pH. The fibril formation
      was strongly promoted by dimerization of K3 through Cys(25). The morphology of
      the fibrils varied depending on the fibril formation conditions and the presence
      or absence of a disulfide bond. Various fibrils had the potential to seed fibril
      formation of full-length beta(2)m accompanied with a characteristic lag phase,
      suggesting that the internal structures are similar.

PMID- 14699108
TI  - Interaction between amino propeptides of type XI procollagen alpha1 chains.
AB  - Type XI collagen is a quantitatively minor yet essential constituent of the
      cartilage extracellular matrix. The amino propeptide of the alpha1 chain remains
      attached to the rest of the molecule for a longer period of time after synthesis
      than the other amino propeptides of type XI collagen and has been localized to
      the surface of thin collagen fibrils. Yeast two-hybrid system was used to
      demonstrate that a homodimer of alpha1(XI) amino propeptide (alpha1(XI)Npp) could
      form in vivo. Interaction was also confirmed using multi-angle laser light
      scattering, detecting an absolute weight average molar mass ranging from the size
      of a monomer to the size of a dimer (25,000-50,000 g/mol), respectively. Binding
      was shown to be saturable by ELISA. An interaction between recombinant
      alpha1(XI)Npp and the endogenous alpha1(XI)Npp was observed, and specificity for
      alpha1(XI)Npp but not alpha2(XI)Npp was demonstrated by co-precipitation. The
      interaction between the recombinant form of alpha1(XI)Npp and the endogenous
      alpha1(XI)Npp resulted in a stable association during the regeneration of
      cartilage extracellular matrix by fetal bovine chondrocytes maintained in pellet
      culture, generating a protein that migrated with an apparent molecular mass of 50
      60 kDa on an SDS-polyacrylamide gel.

PMID- 14699109
TI  - Receptor/transporter-independent targeting of functional peptides across the
      plasma membrane.
AB  - Targeting of peptides, proteins, and other functional cargo into living cells is
      contingent upon efficient transport across the plasma membrane barrier. We have
      harnessed the signal sequence hydrophobic region (SSHR) to deliver functional
      cargoes to cultured cells and to experimental animals. We now report evidence
      that two chirally distinct forms of SSHR composed of all l or all d amino acids
      showed similar membrane-translocating activity as assessed by confocal
      microscopy, flow cytometry, and direct fluorescence measurement. An attached
      nuclear localization sequence ferried by the SSHR enantiomers displayed similar
      intracellular function by inhibiting inducible nuclear import of transcription
      factor nuclear factor kappa B and suppressing nuclear factor kappa B-dependent
      gene expression of cytokines. A nuclear localization sequence comprised of a
      positively charged cluster of amino acids was rapidly translocated by SSHR
      enantiomers to the interior of unilamellar phospholipid vesicles. These findings
      indicate that the SSHR translocates functional peptides directly through the
      plasma membrane phospholipid bilayer without involving chirally specific
      receptor/transporter mechanisms. This mechanism of SSHR translocation is suitable
      for facile delivery of biologically active peptides for cell-based and animal
      based functional proteomic studies.

PMID- 14699110
TI  - Evidence for up-regulation of the endogenous Na-K-2Cl co-transporter by molecular
      interactions with the anion exchanger tAE1 expressed in Xenopus oocyte.
AB  - Expression of trout anion exchanger 1 (tAE1) in Xenopus oocyte led to the
      stimulation of a Na(+)- and Cl(-)-dependent Rb influx. Functional features and
      pharmacological data strongly suggest that this Rb influx is mediated by the
      endogenous Na-K-2Cl (NKCC) co-transporter. The functional relationship between
      expression of tAE1 and activation of the NKCC co-transporter was investigated.
      Indeed, it was shown previously that tAE1 expressed in Xenopus oocyte induces a
      strong anion conductance which is correlated with an increased taurine
      permeability. Measurements of intracellular ion contents ruled out the
      involvement of any modification of known electrochemical parameters in NKCC co
      transporter activation by tAE1. Furthermore, using chimera of tAE1 made with AE1
      from other species unable to exhibit anion conductance led to the conclusion that
      there was no correlation between tAE1 anion conductance and NKCC co-transporter
      stimulation. Therefore, a possible molecular interaction between tAE1 and the
      NKCC co-transporter was investigated. Our results clearly show that NKCC
      activation is dependent upon the C-terminal part of tAE1. Chimeric constructions
      where tAE1 C-terminal part was substituted by the corresponding part of mouse AE1
      abolished co-transporter activation. Moreover, steric encumbrance on the C
      terminal end of tAE1 with a specific antibody or with a protein fusion also
      prevented the co-transporter activation. These data suggest a new role for some
      anion exchangers in controlling other transporter activity by molecular
      interactions.

PMID- 14699111
TI  - Docking interactions in the c-Jun N-terminal kinase pathway.
AB  - The c-Jun N-terminal kinase (JNK) signaling pathway is a major mediator of stress
      responses in cells. Similar to other mitogen-activated protein kinases (MAPKs),
      JNK activity is controlled by a cascade of protein kinases and by protein
      phosphatases, including dual-specificity MAPK phosphatases. Components of the JNK
      pathway associate with scaffold proteins that modulate their activities and
      cellular localization. The JNK-interacting protein-1 (JIP-1) scaffold protein
      specifically binds JNK, MAPK kinase 7 (MKK7), and members of the mixed lineage
      kinase (MLK) family, and regulates JNK activation in neurons. In this study we
      demonstrate that distinct regions within the N termini of MKK7 and the MLK family
      member dual leucine zipper kinase (DLK) mediate their binding to JIP-1. We have
      also identified amino acids in JNK required for: (a) binding to JIP-1 and for JIP
      1-mediated JNK activation, (b) docking to MAPK kinase 4 (MKK4) and efficient
      phosphorylation by MKK4, and (c) docking to its substrate c-Jun and efficient c
      Jun phosphorylation. None of the amino acids identified were essential for JNK
      docking to MKK7 or the dual-specificity phosphatase MAPK phosphatase 7 (MKP7).
      These findings uncover molecular determinants of JIP-1 scaffold complex assembly
      and demonstrate that there are overlapping, but also distinct, binding
      determinants within JNK that mediate interactions with scaffold proteins,
      activators, phosphatases, and substrates.

PMID- 14699112
TI  - ZmYS1 functions as a proton-coupled symporter for phytosiderophore- and
      nicotianamine-chelated metals.
AB  - Among higher plants graminaceous species have the unique ability to efficiently
      acquire iron from alkaline soils with low iron solubility by secreting
      phytosiderophores, which are hexadentate metal chelators with high affinity for
      Fe(III). Iron(III)-phytosiderophores are subsequently taken up by roots via YS1
      transporters, that belong to the OPT oligopeptide transporter family. Despite its
      physiological importance at alkaline pH, uptake of Fe-phytosiderophores into
      roots of wild-type maize plants was greater at acidic pH and sensitive to the
      proton uncoupler CCCP. To access the mechanism of Fe-phytosiderophore
      acquisition, ZmYS1 was expressed in an iron uptake-defective yeast mutant and in
      Xenopus oocytes, where ZmYS1-dependent Fe-phytosiderophore transport was
      stimulated at acidic pH and sensitive to CCCP. Electrophysiological analysis in
      oocytes demonstrated that Fephytosiderophore transport depends on proton
      cotransport and on the membrane potential, which allows ZmYS1-mediated transport
      even at alkaline pH. We further investigated substrate specificity and observed
      that ZmYS1 complemented the growth defect of the zinc uptake-defective yeast
      mutant zap1 and transported various phytosiderophore-bound metals into oocytes,
      including zinc, copper, nickel, and, at a lower rate, also manganese and cadmium.
      Unexpectedly, ZmYS1 also transported Ni(II), Fe(II), and Fe(III) complexes with
      nicotianamine, a structural analog of phytosiderophores, which has been shown to
      act as an intracellular metal chelator in all higher plants. Our results show
      that ZmYS1 encodes a proton-coupled broad-range metal-phytosiderophore
      transporter that additionally transports Fe- and Ni-nicotianamine. These
      biochemical properties indicate a novel role of YS1 transporters for heavy metal
      homeostasis in plants.

PMID- 14699113
TI  - Formation of highly stable chimeric trimers by fusion of an adenovirus fiber
      shaft fragment with the foldon domain of bacteriophage t4 fibritin.
AB  - The folding of beta-structured, fibrous proteins is a largely unexplored area. A
      class of such proteins is used by viruses as adhesins, and recent studies
      revealed novel beta-structured motifs for them. We have been studying the folding
      and assembly of adenovirus fibers that consist of a globular C-terminal domain, a
      central fibrous shaft, and an N-terminal part that attaches to the viral capsid.
      The globular C-terminal, or "head" domain, has been postulated to be necessary
      for the trimerization of the fiber and might act as a registration signal that
      directs its correct folding and assembly. In this work, we replaced the head of
      the fiber by the trimerization domain of the bacteriophage T4 fibritin, termed
      "foldon." Two chimeric proteins, comprising the foldon domain connected at the C
      terminal end of four fiber shaft repeats with or without the use of a natural
      linker sequence, fold into highly stable, SDS-resistant trimers. The structural
      signatures of the chimeric proteins as seen by CD and infrared spectroscopy are
      reported. The results suggest that the foldon domain can successfully replace the
      fiber head domain in ensuring correct trimerization of the shaft sequences.
      Biological implications and implications for engineering highly stable, beta
      structured nanorods are discussed.

PMID- 14699114
TI  - Fibrillar amyloid protein present in atheroma activates CD36 signal transduction.
AB  - The self-association of proteins to form amyloid fibrils has been implicated in
      the pathogenesis of a number of diseases including Alzheimer's, Parkinson's, and
      Creutzfeldt-Jakob diseases. We recently reported that the myeloid scavenger
      receptor CD36 initiates a signaling cascade upon binding to fibrillar beta
      amyloid that stimulates recruitment of microglia in the brain and production of
      inflammatory mediators. This receptor plays a key role in the pathogenesis of
      atherosclerosis, prompting us to evaluate whether fibrillar proteins were present
      in atherosclerotic lesions that could initiate signaling via CD36. We show that
      apolipoprotein C-II, a component of very low and high density lipoproteins,
      readily forms amyloid fibrils that initiate macrophage inflammatory responses
      including reactive oxygen production and tumor necrosis factor alpha expression.
      Using macrophages derived from wild type and Cd36(-/-) mice to distinguish CD36
      specific events, we show that fibrillar apolipoprotein C-II activates a signaling
      cascade downstream of this receptor that includes Lyn and p44/42 MAPKs.
      Interruption of this signaling pathway through targeted deletion of Cd36 or
      blocking of p44/42 MAPK activation inhibits macrophage tumor necrosis factor
      alpha gene expression. Finally, we demonstrate that apolipoprotein C-II in human
      atheroma co-localizes to regions positive for markers of amyloid and macrophage
      accumulation. Together, these data characterize a CD36-dependent signaling
      cascade initiated by fibrillar amyloid species that may promote atherogenesis.

PMID- 14699115
TI  - Mitochondrial import receptors Tom20 and Tom22 have chaperone-like activity.
AB  - Mitochondrial preproteins are synthesized in the cytosol with N-terminal signal
      sequences (presequences) or internal targeting signals. Generally, preproteins
      with presequences are initially recognized by Tom20 (translocase of the outer
      membrane) and, subsequently, by Tom22, whereas hydrophobic preproteins with
      internal targeting signals are first recognized by Tom70. Recent studies suggest
      that Tom70 associates with molecular chaperones, thereby maintaining their
      substrate preproteins in an import-competent state. However, such a function has
      not been reported for other Tom component(s). Here, we investigated a role for
      Tom20 in preventing substrate preproteins from aggregating. In vitro binding
      assays showed that Tom20 binds to guanidinium chloride unfolded substrate
      proteins regardless of the presence or absence of presequences. This suggests
      that Tom20 functions as a receptor not only for presequences but also for mature
      portions exposed in unfolded preproteins. Aggregation suppression assays on
      citrate synthase showed that the cytosolic domain of Tom20 has a chaperone-like
      activity to prevent this protein from aggregating. This activity was inhibited by
      a presequence peptide, suggesting that the binding site of Tom20 for presequence
      is identical or close to the active site for the chaperone-like activity. The
      cytosolic domain of Tom22 also showed a similar activity for citrate synthase,
      whereas Tom70 did not. These results suggest that the cytosolic domains of Tom20
      and Tom22 function to maintain their substrate preproteins unfolded and prevent
      them from aggregating on the mitochondrial surface.

PMID- 14699116
TI  - Cytoplasmic domain-mediated dimerizations of toll-like receptor 4 observed by
      beta-lactamase enzyme fragment complementation.
AB  - Toll-like receptors (TLRs) detect the presence of microbial challenge and
      initiate innate immune defensive responses. In this work we have explored the
      mechanism and role of TLR dimerization in signal transduction using the newly
      developed technique of beta-lactamase protein fragment complementation, among
      others. We observed that TLR4 interactions with itself, with MyD88, or with TLR2
      were accurately reported by the enzyme complementation technique. That technique,
      as well as co-immunoprecipitation, transfection-initiated cell activation, and
      site-directed mutagenesis all suggest an important role for TLR intracellular
      domains in receptor dimerization. These findings broaden our understanding of TLR
      self-interactions as well as heterodimer formation.

PMID- 14699118
TI  - Enhancement of phototransduction g protein-effector interactions by
      phosphoinositides.
AB  - Light responses in photoreceptor cells are mediated by the action of the G
      protein transducin (G(t)) on the effector enzyme cGMP phosphodiesterase (PDE6) at
      the surface of disk membranes. The enzymatic components needed for
      phosphoinositide-based signaling are known to be present in rod cells, but it has
      remained uncertain what role phosphoinositides play in vertebrate
      phototransduction. Reconstitution of PDE6 and activated G(alphat), on the surface
      of large unilamellar vesicles containing d-myo-phosphatidylinositol-4,5
      bisphosphate (PI(4,5)P(2)), stimulated PDE activity nearly 4-fold above the level
      observed with membranes containing no phosphoinositides, whereas G protein
      independent activation by trypsin was unaffected by the presence of
      phosphoinositides. PDE activity was similarly stimulated by d-myo
      phosphatidylinositol-3,4-bisphosphate and d-myo-phosphatidylinositol-4-phosphate
      (PI(4)P), but much less by d-myo-phosphatidylinositol-5-phosphate (PI(5)P) or d
      myo-phosphatidylinositol-3,5-bisphosphate. Incubation of rod outer segment
      membranes with phosphoinositide-specific phospholipase C decreased G protein
      stimulated activation of endogenous PDE6, but not trypsin-stimulated PDE
      activity. Binding experiments using phosphoinositide-containing vesicles revealed
      patterns of PDE6 binding and PDE6-enhanced G(alphat)-GTPgammaS binding,
      consistent with the activation profile PI(4,5)P(2) > PI(4)P > PI(5)P
      approximately control vesicles. These results suggest that enhancement of
      effector-G protein interactions represents a possible mechanism for modulation of
      phototransduction gain by changes in phosphoinositide levels, perhaps occurring
      in response to longterm changes in illumination or other environmental cues.

PMID- 14699117
TI  - Role of the histidine triad-like motif in nucleotide hydrolysis by the rotavirus
      RNA-packaging protein NSP2.
AB  - Octamers formed by the nonstructural protein NSP2 of rotavirus are proposed to
      function as molecular motors in the packaging of the segmented double-stranded
      RNA genome. The octamers have RNA binding, helix unwinding, and Mg(2+)-dependent
      NTPase activities and play a crucial role in assembly of viral replication
      factories (viroplasms). Comparison of x-ray structures has revealed significant
      structural homology between NSP2 and the histidine triad (HIT) family of
      nucleotidyl hydrolases, which in turn has suggested the location of the active
      site for NTP hydrolysis in NSP2. Consistent with the structural predictions, we
      show here using site-specific mutagenesis and ATP docking simulations that the
      active site for NTP hydrolysis is localized to residues within a 25-A-deep cleft
      between the C- and N-terminal domains of the NSP2 monomer. Although lacking the
      precise signature HIT motif (HOHOHOO where O is a hydrophobic residue), our
      analyses demonstrate that histidines (His(221) and His(225)) represent critical
      residues of the active site. Similar to events occurring during nucleotide
      hydrolysis by HIT proteins, NTP hydrolysis by NSP2 was found to produce a short
      lived phosphorylated intermediate. Evaluation of the biological importance of the
      NTPase activity of NSP2 by transient expression in mammalian cells showed that
      such activity has no impact on the ability of NSP2 to induce the
      hyperphosphorylation of NSP5 or to interact with NSP5 to form viroplasm-like
      structures. Hence the NTPase activity of NSP2 probably has a role subsequent to
      the formation of viroplasms, consistent with its suspected involvement in RNA
      packaging and/or replication.

PMID- 14699119
TI  - Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase
      MELK and involvement of splicing factor NIPP1.
AB  - NIPP1 is a ubiquitous nuclear protein that is required for spliceosome assembly.
      We report here that the phosphothreonine-binding Forkhead-associated domain of
      NIPP1 interacts with the cell cycle-regulated protein Ser/Thr kinase MELK
      (maternal embryonic leucine zipper kinase). The NIPP1-MELK interaction was
      critically dependent on the phosphorylaton of Thr-478 of MELK and was increased
      in lysates from mitotically arrested cells. Recombinant MELK was a potent
      inhibitor of an early step of spliceosome assembly in nuclear extracts. This
      splicing defect was also seen with a kinase-dead mutant but was absent after
      mutation (T478A) of the NIPP1 binding site of MELK, indicating a mediatory role
      for NIPP1. Our data suggest that MELK has a role in the cell cycle-regulated
      control of pre-mRNA splicing.

PMID- 14699120
TI  - Tyrosine kinase, p56lck-induced cell motility, and urokinase-type plasminogen
      activator secretion involve activation of epidermal growth factor
      receptor/extracellular signal regulated kinase pathways.
AB  - We have recently reported that tyrosine kinase, p56(lck) regulates cell motility
      and nuclear factor kappaB-mediated secretion of urokinase-type plasminogen
      activator (uPA) through tyrosine phosphorylation of IkappaBalpha following
      hypoxia/reoxygenation (Mahabeleshwar, G. H., and Kundu, G. C. (2003) J. Biol.
      Chem. 278, 52598-52612). However, the role of hypoxia/reoxygenation (H/R) on
      ERK1/2-mediated uPA secretion and cell motility and the involvement of p56(lck)
      and EGF receptor in these processes in breast cancer cells is not well defined.
      We provide here evidence that H/R induces Lck kinase activity and Lck-dependent
      tyrosine phosphorylation of EGF receptor in highly invasive (MDA-MB-231) and low
      invasive (MCF-7) breast cancer cells. H/R also stimulates MEK-1 and ERK1/2
      phosphorylations, and H/R-induced phosphorylations were suppressed by the
      dominant negative form of Lck (DN Lck, K273R) as well as pharmacological
      inhibitors of EGF receptor and Lck indicating that EGF receptors and Lck are
      involved in these processes. Transfection of these cells with wild type Lck or
      Lck F505 (Y505F) but not with Lck F394 (Y394F) induced phosphorylations of EGF
      receptor followed by MEK-1 and ERK1/2, suggesting that Lck is upstream of EGF
      receptor and Tyr-394 of Lck is crucial for these processes. H/R also induced uPA
      secretion and cell motility in these cells. DN Lck and inhibitors of Lck, EGF
      receptor, and MEK-1 suppressed H/R-induced uPA secretion and cell motility. To
      our knowledge, this is the first report that p56(lck) in presence of H/R
      regulates MEK-1-dependent ERK1/2 phosphorylation and uPA secretion through
      tyrosine phosphorylation of EGF receptor, and it further demonstrates that all of
      these signaling molecules ultimately control the motility of breast cancer cells.

PMID- 14699121
TI  - The thrH gene product of Pseudomonas aeruginosa is a dual activity enzyme with a
      novel phosphoserine:homoserine phosphotransferase activity.
AB  - The thrH gene product of Pseudomonas aeruginosa has been shown to complement both
      homoserine kinase (thrB gene product) and phosphoserine phosphatase (serB gene
      product) activities in vivo. Sequence comparison has revealed that ThrH is
      related to phosphoserine phosphatases (PSP, EC 3.1.3.3) and belongs to the l-2
      haloacid dehalogenase-like protein superfamily. We have solved the crystal
      structures of ThrH in the apoform and in complex with a bound product phosphate.
      The structure confirms an overall fold similar to that of PSP. Most of the
      catalytic residues of PSP are also conserved in ThrH, suggesting that similar
      catalytic mechanisms are used by both enzymes. Spectrophotometry-based in vitro
      assays show that ThrH is indeed a phosphoserine phosphatase with a K(m) of 0.207
      mm and k(cat) of 13.4 min(-1), comparable with those of other PSPs. More
      interestingly, using high pressure liquid chromatography-based assays, we have
      demonstrated that ThrH is able to further transfer the phosphoryl group to
      homoserine using phosphoserine as the phosphoryl group donor, indicating that
      ThrH has a novel phosphoserine:homoserine phosphotransferase activity.

PMID- 14699122
TI  - Induced fit movements and metal cofactor selectivity of class II aldolases:
      structure of Thermus aquaticus fructose-1,6-bisphosphate aldolase.
AB  - Fructose-1,6-bisphosphate (FBP) aldolase is an essential glycolytic enzyme that
      reversibly cleaves its ketohexose substrate into triose phosphates. Here we
      report the crystal structure of a metallo-dependent or class II FBP aldolase from
      an extreme thermophile, Thermus aquaticus (Taq). The quaternary structure reveals
      a tetramer composed of two dimers related by a 2-fold axis. Taq FBP aldolase
      subunits exhibit two distinct conformational states corresponding to loop regions
      that are in either open or closed position with respect to the active site. Loop
      closure remodels the disposition of chelating active site histidine residues. In
      subunits corresponding to the open conformation, the metal cofactor, Co(2+), is
      sequestered in the active site, whereas for subunits in the closed conformation,
      the metal cation exchanges between two mutually exclusive binding loci,
      corresponding to a site at the active site surface and an interior site vicinal
      to the metal-binding site in the open conformation. Cofactor site exchange is
      mediated by rotations of the chelating histidine side chains that are coupled to
      the prior conformational change of loop closure. Sulfate anions are consistent
      with the location of the phosphate-binding sites of the FBP substrate and
      determine not only the previously unknown second phosphate-binding site but also
      provide a mechanism that regulates loop closure during catalysis. Modeling of FBP
      substrate into the active site is consistent with binding by the acyclic keto
      form, a minor solution species, and with the metal cofactor mediating keto bond
      polarization. The Taq FBP aldolase structure suggests a structural basis for
      different metal cofactor specificity than in Escherichia coli FBP aldolase
      structures, and we discuss its potential role during catalysis. Comparison with
      the E. coli structure also indicates a structural basis for thermostability by
      Taq FBP aldolase.

PMID- 14699123
TI  - Identification of the IgE-binding epitope in omega-5 gliadin, a major allergen in
      wheat-dependent exercise-induced anaphylaxis.
AB  - Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a severe IgE-mediated
      allergic reaction provoked by the combination of wheat-ingestion with intensive
      physical exercise over the next few hours. Among wheat proteins, omega-5 gliadin,
      which is one of the components of fast omega-gliadin, has been reported as a
      major allergen in the anaphylaxis. In this study, we detected IgE-binding
      epitopes within the primary sequence of omega-5 gliadin using arrays of
      overlapping peptides synthesized on derivatized cellulose membranes. Sera from
      four patients with WDEIA having specific IgE to the fast omega-gliadin were used
      to probe the membrane. Seven epitopes, QQIPQQQ, QQLPQQQ, QQFPQQQ, QQSPEQQ,
      QQSPQQQ, QQYPQQQ, and PYPP, were detected within the primary sequence of omega-5
      gliadin. By using sera of 15 patients, 4 of them, QQIPQQQ, QQFPQQQ, QQSPEQQ, and
      QQSPQQQ, were found to be dominant epitopes. Mutational analysis of the QQIPQQQ
      and QQFPQQQ indicated that amino acids at positions Gln(1), Pro(4), Gln(5),
      Gln(6), and Gln(7) were critical for IgE binding. These results will provide a
      useful tool for developing safer wheat products in addition to diagnostic and
      immunotherapy techniques for WDEIA.

PMID- 14699124
TI  - DUB-3, a cytokine-inducible deubiquitinating enzyme that blocks proliferation.
AB  - Previous studies have identified the DUB family of cytokine-regulated murine
      deubiquitinating enzymes, which play a role in the control of cell proliferation
      and survival. Through data base analyses and cloning, we have identified a human
      cDNA (DUB-3) that shows significant homology to the known murine DUB family
      members. Northern blotting has shown expression of this gene in a number of
      tissues including brain, liver, and muscle, with two transcripts being apparent
      (1.6 and 1.7 kb). In addition, expression was observed in cell lines including
      those derived from a number of hematopoietic tumors such as the Burkitt's
      lymphoma cell line RAJI. We have also demonstrated that DUB-3, which was shown to
      be an active deubiquitinating enzyme, is induced in response to interleukin-4 and
      interleukin-6 stimulation. Finally, we have demonstrated that constitutive
      expression of DUB-3 blocks proliferation and can initiate apoptosis in both IL-3
      dependent Ba/F3 cells and NIH3T3 fibroblasts. These findings suggest that human
      DUB-3, like the murine DUB family members, is transiently induced in response to
      cytokines and can, when constitutively expressed, block growth factor-dependent
      proliferation.

PMID- 14699125
TI  - The yeast Pdr15p ATP-binding cassette (ABC) protein is a general stress response
      factor implicated in cellular detoxification.
AB  - ATP-binding cassette (ABC) transporters play important roles in drug efflux, but
      some may also function in cellular detoxification. The Pdr15p ABC protein is the
      closest homologue of the multidrug efflux transporter Pdr5p, which mediates
      pleiotropic drug resistance to hundreds of unrelated compounds. In this study, we
      show that the plasma membrane protein Pdr15p displays limited drug transport
      capacity, mediating chloramphenicol and detergent tolerance. Interestingly,
      Pdr15p becomes most abundant when cells exit the exponential growth phase,
      whereas its closest homologue, Pdr5p, disappears after exponential growth.
      Furthermore, in contrast to Pdr5p, Pdr15p is strongly induced by various stress
      conditions including heat shock, low pH, weak acids, or high osmolarity. PDR15
      induction bypasses the Pdr1p/Pdr3p regulators but requires the general stress
      regulator Msn2p, which directly decorates the stress response elements in the
      PDR15 promoter. Remarkably, however, Pdr15p induction bypasses upstream
      components of the high osmolarity glycerol (HOG) pathway including the Hog1p and
      Pbs2p kinases as well as the dedicated HOG cell surface sensors. Our data provide
      evidence for a novel upstream branch of the general stress response pathway
      activating Msn2p. In addition, the results demonstrate a cross-talk between
      stress response and the pleiotropic drug resistance network.

PMID- 14699126
TI  - Role of mitogen-activated protein kinases in 4-hydroxy-2-nonenal-induced actin
      remodeling and barrier function in endothelial cells.
AB  - In vivo and in vitro studies indicate that 4-hydroxy-2-nonenal (4-HNE), generated
      by cellular lipid peroxidation or after oxidative stress, affects endothelial
      permeability and vascular tone. However, the mechanism(s) of 4-HNE-induced
      endothelial barrier function is not well defined. Here we provide evidence for
      the first time on the involvement of mitogen-activated protein kinases (MAPKs) in
      4-HNE-mediated actin stress fiber formation and barrier function in lung
      endothelial cells. Treatment of bovine lung microvascular endothelial cells with
      hydrogen peroxide (H(2)O(2)), as a model oxidant, resulted in accumulation of 4
      HNE as evidenced by the formation of 4-HNE-Michael protein adducts. Exposure of
      cells to 4-HNE, in a dose- and time-dependent manner, decreased endothelial cell
      permeability measured as transendothelial electrical resistance. The 4-HNE
      induced permeability changes were not because of cytotoxicity or endothelial cell
      apoptosis, which occurred after prolonged treatment and at higher concentrations
      of 4-HNE. 4-HNE-induced changes in transendothelial electrical resistance were
      calcium independent, as 4-HNE did not alter intracellular free calcium levels as
      compared with H(2)O(2) or diperoxovanadate. Stimulation of quiescent cells with 4
      HNE (1-100 microm) resulted in phosphorylation of ERK1/2, JNK, and p38 MAPKs, and
      actin cytoskeleton remodeling. Furthermore, pretreatment of bovine lung
      microvascular endothelial cells with PD 98059 (25 microm), an inhibitor of
      MEK1/2, or SP 600125 (25 microm), an inhibitor of JNK, or SB 202190 (25 microm),
      an inhibitor of p38 MAPK, partially attenuated 4-HNE-mediated barrier function
      and cytoskeletal remodeling. These results suggest that the activation of ERK,
      JNK, and p38 MAP kinases is involved in 4-HNE-mediated actin remodeling and
      endothelial barrier function.

PMID- 14699127
TI  - The embryotrophic activity of oviductal cell-derived complement C3b and iC3b, a
      novel function of complement protein in reproduction.
AB  - The oviduct-derived embryotrophic factor, ETF-3, enhances the development of
      trophectoderm and the hatching process of treated embryos. Monoclonal anti-ETF-3
      antibody that abolishes the embryotrophic activity of ETF-3 recognized a 115-kDa
      protein from the conditioned medium of immortalized human oviductal cells. Mass
      spectrometry analysis showed that the protein was complement C3. Western blot
      analysis using an antibody against C3 confirmed the cross-reactivities between
      anti-C3 antibody with ETF-3 and anti-ETF-3 antibody with C3 and its derivatives,
      C3b and iC3b. Both derivatives, but not C3, were embryotrophic. iC3b was most
      efficient in enhancing the development of blastocysts with larger size and higher
      hatching rate, consistent with the previous reported embryotrophic activity of
      ETF-3. Embryos treated with iC3b contained iC3b immunoreactivity. The oviductal
      epithelium produced C3 as evidenced by the presence of C3 immunoreactivity and
      mRNA in the human oviduct and cultured oviductal cells. Cyclical changes in the
      expression of C3 immunoreactivity and mRNA were also found in the mouse oviduct
      with the highest expression at the estrus stage. Molecules involving in the
      conversion of C3b to iC3b and binding of iC3b were present in the human oviduct
      (factor I) and mouse preimplantation embryo (Crry and CR3), respectively. In
      conclusion, the present data showed that the oviduct produced C3/C3b, which was
      converted to iC3b to stimulate embryo development.

PMID- 14699128
TI  - Complex distribution, not absolute amount of adiponectin, correlates with
      thiazolidinedione-mediated improvement in insulin sensitivity.
AB  - Adiponectin is an adipocyte-specific secretory protein that circulates in serum
      as a hexamer of relatively low molecular weight (LMW) and a larger multimeric
      structure of high molecular weight (HMW). Serum levels of the protein correlate
      with systemic insulin sensitivity. The full-length protein affects hepatic
      gluconeogenesis through improved insulin sensitivity, and a proteolytic fragment
      of adiponectin stimulates beta oxidation in muscle. Here, we show that the ratio,
      and not the absolute amounts, between these two oligomeric forms (HMW to LMW) is
      critical in determining insulin sensitivity. We define a new index, S(A), that
      can be calculated as the ratio of HMW/(HMW + LMW). db/db mice, despite similar
      total adiponectin levels, display decreased S(A) values compared with wild type
      littermates, as do type II diabetic patients compared with insulin-sensitive
      individuals. Furthermore, S(A) improves with peroxisome proliferator-activated
      receptor-gamma agonist treatment (thiazolidinedione; TZD) in mice and humans. We
      demonstrate that changes in S(A) in a number of type 2 diabetic cohorts serve as
      a quantitative indicator of improvements in insulin sensitivity obtained during
      TZD treatment, whereas changes in total serum adiponectin levels do not correlate
      well at the individual level. Acute alterations in S(A) (DeltaS(A)) are strongly
      correlated with improvements in hepatic insulin sensitivity and are less relevant
      as an indicator of improved muscle insulin sensitivity in response to TZD
      treatment, further underscoring the conclusions from previous clamp studies that
      suggested that the liver is the primary site of action for the full-length
      protein. These observations suggest that the HMW adiponectin complex is the
      active form of this protein, which we directly demonstrate in vivo by its ability
      to depress serum glucose levels in a dose-dependent manner.

PMID- 14699129
TI  - Identification of two novel components of the human NDC80 kinetochore complex.
AB  - Proper kinetochore function is essential for the accurate segregation of
      chromosomes during mitosis. Kinetochores provide the attachment sites for spindle
      microtubules and are required for the alignment of chromosomes at the metaphase
      plate (chromosome congression). Components of the conserved NDC80 complex are
      required for chromosome congression, and their disruption results in mitotic
      arrest accompanied by multiple spindle aberrations. To better understand the
      function of the NDC80 complex, we have identified two novel subunits of the human
      NDC80 complex, termed human SPC25 (hSPC25) and human SPC24 (hSPC24), using an
      immunoaffinity approach. hSPC25 interacted with HEC1 (human homolog of yeast
      Ndc80) throughout the cell cycle and localized to kinetochores during mitosis.
      RNA interference-mediated depletion of hSPC25 in HeLa cells caused aberrant
      mitosis, followed by cell death, a phenotype similar to that of cells depleted of
      HEC1. Loss of hSPC25 also caused multiple spindle aberrations, including
      elongated, multipolar, and fractured spindles. In the absence of hSPC25, MAD1 and
      HEC1 failed to localize to kinetochores during mitosis, whereas the kinetochore
      localization of BUB1 and BUBR1 was largely unaffected. Interestingly, the
      kinetochore localization of MAD1 in cells with a compromised NDC80 function was
      restored upon microtubule depolymerization. Thus, hSPC25 is an essential
      kinetochore component that plays a significant role in proper execution of
      mitotic events.

PMID- 14699130
TI  - Glitazones differentially regulate primary astrocyte and glioma cell survival.
      Involvement of reactive oxygen species and peroxisome proliferator-activated
      receptor-gamma.
AB  - The glitazones or thiazolidinediones are ligands of the peroxisome proliferator
      activated receptor gamma (PPARgamma). The glitazones are used in the treatment of
      diabetes, regulate adipogenesis, inflammation, cell proliferation, and induce
      apoptosis in several cancer cell types. High grade astrocytomas are rapidly
      growing tumors derived from astrocytes, for which new treatments are needed. We
      determined the effects of two glitazones, ciglitazone and the therapeutic
      rosiglitazone, on the survival of serum-deprived primary rat astrocytes and
      glioma cell lines C6 and U251, which were assessed by the methylthiazolyl
      tetrazolium assay and lactate dehydrogenase release. Rosiglitazone (5-20 microM)
      decreased survival of glioma cells without affecting primary astrocytes, whereas
      ciglitazone at 20 microM was toxic for both cell types. Ciglitazone at 10 microM
      was cytoprotective for primary astrocytes but toxic to glioma cells. Cell death
      induced by ciglitazone, but not rosiglitazone, presented apoptotic features
      (Hoechst staining and externalization of phosphatidylserine). Two mechanisms to
      explain cytotoxicity were investigated: activation of PPARgamma and production of
      reactive oxygen species (ROS). PPARgamma does not seem to be the main mechanism
      involved, because the order of efficacy for cytotoxicity, ciglitazone >
      rosiglitazone, was inverse of their reported affinities for activating PPARgamma.
      In addition, GW9662, an inhibitor of PPARgamma, only slightly attenuated
      cytotoxicity. However, the rapid increase in ROS production and the marked
      reduction of cell death with the antioxidants ebselen and N-acetylcysteine,
      indicate that ROS have a key role in glitazone cytotoxicity. Ciglitazone caused a
      dose-dependent and rapid loss (in minutes) of mitochondrial membrane potential in
      glioma cells. Therefore, mitochondria are a likely source of ROS and early
      targets of glitazone cytotoxicity. Our results highlight the potential of
      rosiglitazone and related compounds for the treatment of astrogliomas.

PMID- 14699132
TI  - Microtubule depolymerization rapidly collapses capillary tube networks in vitro
      and angiogenic vessels in vivo through the small GTPase Rho.
AB  - Maintenance of endothelial cell tube integrity is dependent on an intact
      cytoskeleton. We present data indicating that rapid collapse of endothelial
      tubular networks in vitro occurs in a dose-dependent manner after administration
      of microtubule-depolymerizing reagents but not after actin depolymerization.
      Pretreatment of endothelial cell networks with C3 exoenzyme or recombinant
      adenoviruses expressing dominant negative RhoA resulted in complete blockade of
      tube collapse, indicating a role for RhoA in these events. Microtubule
      depolymerization also resulted in activation of RhoA, whereas increased
      expression of constitutively active RhoA induced cell rounding and apoptosis of
      endothelial cells. Furthermore, following treatment with the chemotherapeutic
      agent vinblastine, rapid capillary tube network collapse occurred followed by
      endothelial cell apoptosis. Vinblastine, but not control agents, induced cleavage
      of procaspase-3, procaspase-9, and procaspase-8, along with the known caspase
      targets p21-activated kinase-2 and gelsolin, indicating that tube collapse caused
      a defined apoptotic response. Using a model of vascular endothelial growth factor
      stimulated angiogenesis in vivo, vinblastine treatment also resulted in collapse
      and apoptosis of angiogenic blood vessels. Apoptotic endothelial cells stained
      strongly for cleaved caspase-3, and terminal dUTP nick-end labeling staining
      revealed fragmented nuclei in vinblastine-treated but not control angiogenic
      areas. Together, these findings indicate that microtubule-depolymerizing agents
      directly induce endothelial network collapse in vitro and in vivo leading to
      endothelial cell apoptosis in a manner dependent on the small GTPase, RhoA. In
      addition, these findings reveal a novel function for microtubule disrupting
      chemotherapeutic agents, namely their ability to rapidly collapse newly formed
      angiogenic vessels, which may contribute to their effectiveness in limiting
      angiogenesis and tumor growth.

PMID- 14699131
TI  - Interaction of TRPC2 and TRPC6 in erythropoietin modulation of calcium influx.
AB  - Erythropoietin (Epo) modulates calcium influx through voltage-independent calcium
      permeable channel(s). Here, we characterized the expression of transient receptor
      potential channels (TRPCs) in primary erythroid cells and examined their
      regulation. Erythroblasts were isolated from the spleens of phenylhydrazine
      treated mice, and Epo stimulation resulted in a significant and dose-dependent
      increase in [Ca](i). Among the classical TRPC channels, expression of three N
      terminal splice variants of TRPC2 (clones 14, 17, and alpha) and of TRPC6 were
      demonstrated in these erythroblasts by both reverse transcriptase-PCR and Western
      blotting. Confocal microscopy confirmed localization to the plasma membrane. To
      determine the function of individual TRPC channels in erythropoietin modulation
      of calcium influx, digital video imaging was used to measure calcium influx
      through these TRPCs in a Chinese hamster ovary (CHO) cell model. Single CHO-S
      cells, expressing transfected Epo-R, were identified by detection of green
      fluorescent protein. Cells that express transfected TRPCs were identified by
      detection of blue fluorescent protein. [Ca](i) was monitored with Fura Red. Epo
      stimulation of CHO-S cells transfected with single TRPC2 isoforms (clone 14, 17,
      or alpha) and Epo-R resulted in a significant increase in [Ca](i). This was not
      observed in cells transfected with Epo-R and TRPC6. In addition, coexpression of
      TRPC6 with TRPC2 and Epo-R inhibited the increase in [Ca](i) observed after Epo
      stimulation. Immunoprecipitation experiments demonstrated that TRPC2 associates
      with TRPC6, indicating that these TRPCs can form multimeric channels. These data
      demonstrate that specific TRPCs are expressed in primary erythroid cells and that
      two of these channels, TRPC2 and TRPC6, can interact to modulate calcium influx
      stimulated by erythropoietin.

PMID- 14699133
TI  - Comparative kinetics of nucleotide analog incorporation by vent DNA polymerase.
AB  - Comparative kinetic and structural analyses of a variety of polymerases have
      revealed both common and divergent elements of nucleotide discrimination.
      Although the parameters for dNTP incorporation by the hyperthermophilic archaeal
      Family B Vent DNA polymerase are similar to those previously derived for Family A
      and B DNA polymerases, parameters for analog incorporation reveal alternative
      strategies for discrimination by this enzyme. Discrimination against
      ribonucleotides was characterized by a decrease in the affinity of NTP binding
      and a lower rate of phosphoryl transfer, whereas discrimination against ddNTPs
      was almost exclusively due to a slower rate of phosphodiester bond formation.
      Unlike Family A DNA polymerases, incorporation of 9-[(2-hydroxyethoxy)methyl]X
      triphosphates (where X is adenine, cytosine, guanine, or thymine; acyNTPs) by
      Vent DNA polymerase was enhanced over ddNTPs via a 50-fold increase in phosphoryl
      transfer rate. Furthermore, a mutant with increased propensity for nucleotide
      analog incorporation (Vent(A488L) DNA polymerase) had unaltered dNTP
      incorporation while displaying enhanced nucleotide analog binding affinity and
      rates of phosphoryl transfer. Based on kinetic data and available structural
      information from other DNA polymerases, we propose active site models for dNTP,
      ddNTP, and acyNTP selection by hyperthermophilic archaeal DNA polymerases to
      rationalize structural and functional differences between polymerases.

PMID- 14699134
TI  - A gibberellin-induced nuclease is localized in the nucleus of wheat aleurone
      cells undergoing programmed cell death.
AB  - The aleurone layer of cereal grains undergoes a gibberellin-regulated process of
      programmed cell death (PCD) following germination. We have applied a combination
      of ultrastructural and biochemical approaches to analyze aleurone PCD in intact
      wheat grains. The terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling assay revealed that PCD was initiated in aleurone cells proximal to the
      embryo and then extended to distal cells. DNA fragmentation and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis revealed
      PCD of aleurone cells in maize grains, although the process was delayed as
      compared with wheat. Aleurone cells undergoing PCD showed a rapid vacuolation
      with high lytic activity in the cytoplasm, whereas the nucleus, which adopted an
      irregular shape, appeared essentially intact and showed symptoms of degradation
      at the end of the process. A nuclease activity was identified localized in the
      nucleus of aleurone cells undergoing PCD, just prior to the appearance of DNA
      laddering. This nuclease was induced by gibberellic acid treatment and was not
      detected when gibberellin synthesis was inhibited or in gibberellic acid
      insensitive mutants. This nuclease was activated by Ca(2+) and Mg(2+), strongly
      inhibited by Zn(2+), and showed optimum activity at neutral pH, resembling
      nucleases involved in apoptosis of animal cells.

PMID- 14699135
TI  - Tyrosine-to-cysteine modification of human alpha-synuclein enhances protein
      aggregation and cellular toxicity.
AB  - The deposition of alpha-synuclein and other cellular proteins in Lewy bodies in
      midbrain dopamine neurons is a pathological hallmark of Parkinson's disease.
      Nitrative and oxidative stress can induce alpha-synuclein protein aggregation,
      possibly initiated by the formation of stable cross-linking dimers. To determine
      whether enhanced dimer formation can accelerate protein aggregation and increase
      cellular toxicity, we have substituted cysteine for tyrosine at positions 39,
      125, 133, and 136 in human wild-type (WT) alpha-synuclein, and in A53T and A30P
      mutant alpha-synuclein. To reduce the likelihood of cross-linking, phenylalanine
      was substituted for tyrosine at the same sites. We have found that overexpression
      of Y39C or Y125C mutant proteins leads to increased intracellular inclusions and
      apoptosis in a rat dopaminergic cell line (N27 cells) and in human embryonic
      kidney 293 cells. Expression of Y133C, Y136C, and all four Tyr-to-Phe mutations
      were not more cytotoxic than WT control. Exposure to oxidative stress increased
      Y39C and Y125C alpha-synuclein aggregation and toxicity. Dimers and oligomers
      were found in Triton X-100-soluble fractions from adenovirus-mediated
      overexpression of Y39C and Y125C in N27 cells. In contrast, WT beta-synuclein and
      all four Tyr-to-Cys mutant beta-synucleins did not cause protein aggregation and
      cell death. We conclude that cysteine substitution at critical positions in the
      alpha-synuclein molecule can increase dimer formation and accelerate protein
      aggregation and cellular toxicity of alpha-synuclein.

PMID- 14699136
TI  - A cluster of aromatic amino acids in the i2 loop plays a key role for Gs coupling
      in prostaglandin EP2 and EP3 receptors.
AB  - To assess the structural requirements for G(s) coupling by prostaglandin E
      receptors (EPs), the G(s)-coupled EP2 and G(i)-coupled EP3beta receptors were
      used to generate hybrid receptors. Interchanging of the whole i2 loop and its N
      terminal half (i2N) had no effect on the binding of both receptors expressed in
      HEK293 cells. Agonist-induced cAMP formation was observed in wild type EP2 but
      not in the i2 loop- or i2N-substituted EP2. Wild type EP3beta left cAMP levels
      unaffected, whereas i2 loop- and i2N-substituted EP3 gained agonist-induced
      adenylyl cyclase stimulation. In EP2, the ability to stimulate cAMP formation was
      lost by mutation of Tyr(143) into Ala but retained by mutations into Phe, Trp,
      and Leu. Consistent with this observation, substitution of the equivalent
      His(140) enabled EP3beta to stimulate cAMP formation with the rank order of Phe >
      Tyr > Trp > Leu. The point mutation of His(140) into Phe was effective in another
      EP3 variant in which its C-terminal tail is different or lacking. Simultaneous
      mutation of the adjacent Trp(141) to Ala but not at the following Tyr(142)
      weakened the acquired ability to stimulate cAMP levels in the EP3 mutant.
      Mutation of EP2 at adjacent Phe(144) to Ala but not at Tyr(145) reduced the
      efficiency of agonist-induced cAMP formation. In Chinese hamster ovary cells
      stably expressing G(s)-acquired EP3 mutant, an agonist-dependent cAMP formation
      was observed, and pertussis toxin markedly augmented cAMP formation. These
      results suggest that a cluster of hydrophobic aromatic amino acids in the i2 loop
      plays a key role for G(s) coupling.

PMID- 14699137
TI  - Inhibition of human p53 basal transcription by down-regulation of protein kinase
      Cdelta.
AB  - In response to DNA damage, signal transduction pathways are activated that result
      in the increase of p53 protein levels, leading to either growth arrest or
      apoptosis. Protein kinase C (PKC) delta has been implicated as a tumor suppressor
      that is down-regulated by tumor-promoting phorbol esters in both mouse skin and
      cell culture models. We report here that the tumor-promoting phorbol ester 12-O
      tetradecanoylphorbol-13-acetate prevents DNA damage-induced up-regulation of p53
      by down-regulating PKC delta. Regulation of p53 in response to stress most
      commonly occurs by preventing ubiquitination and degradation of the p53 protein.
      Surprisingly, suppression of p53 expression by inhibition of PKC delta was caused
      by the inhibition of p53 synthesis, not increased degradation of p53 protein.
      Inhibiting PKC delta blocked both basal transcription of the human p53 gene and
      initiation of transcription from the human p53 promoter. Therefore, the tumor
      suppressing effects of PKC delta are mediated at least in part through activating
      p53 transcription.

PMID- 14699138
TI  - Ki-1/57 interacts with RACK1 and is a substrate for the phosphorylation by
      phorbol 12-myristate 13-acetate-activated protein kinase C.
AB  - Ki-1/57, the 57-kDa human protein antigen recognized by the CD30 antibody Ki-1,
      is a cytoplasmic and nuclear protein that is phosphorylated on serine and
      threonine residues. When isolated from the Hodgkin's lymphoma analogous cell line
      L540 Ki-1/57 co-immunoprecipitated with a Thr/Ser protein kinase activity. It has
      been also found to interact with hyaluronic acid and has therefore been termed
      intracellular IHABP4 (hyaluronan-binding protein 4). Recent studies demonstrated,
      however, that Ki-1/57 engages in specific interaction with the chromo-helicase
      DNA-binding domain protein 3, a nuclear protein involved in chromatin remodeling
      and transcription regulation. We used the yeast two-hybrid system to find
      proteins interacting with Ki-1/57 and identified the adaptor protein RACK1
      (receptor of activated kinase 1). Next, we confirmed this interaction in vitro
      and in vivo, performed detailed mapping studies of the interaction sites of Ki
      1/57 and RACK-1, and demonstrated that Ki-1/57 also co-precipitates with protein
      kinase C (PKC) when isolated from phorbol 12-myristate 13-acetate (PMA)-activated
      L540 tumor cells and is a substrate for PKC phosphorylation in vitro and in vivo.
      Interestingly, the interaction of Ki-1/57 with RACK1 is abolished upon activation
      of L540 cells with PMA, which results in the phosphorylation of Ki-1/57 and its
      exit from the nucleus. Taken together, our data suggest that Ki-1/57 forms a
      stable complex with RACK-1 in unstimulated cells and upon PMA stimulation gets
      phosphorylated on threonine residues located at its extreme C terminus. These
      events associate Ki-1/57 with the RACK1/PKC pathway and may be important for the
      regulation of its cellular functions.

PMID- 14699139
TI  - Low density lipoprotein receptor-related protein-1 promotes beta1 integrin
      maturation and transport to the cell surface.
AB  - Low density lipoprotein receptor-related protein-1 (LRP-1) mediates the
      endocytosis of multiple plasma membrane proteins and thereby models the
      composition of the cell surface. LRP-1 also functions as a catabolic receptor for
      fibronectin, limiting fibronectin accumulation in association with cells. The
      goal of the present study was to determine whether LRP-1 regulates cell surface
      levels of the beta(1) integrin subunit. We hypothesized that LRP-1 may down
      regulate cell surface beta(1) by promoting its internalization; however,
      unexpectedly, LRP-1 expression was associated with a substantial increase in cell
      surface beta(1) integrin in two separate cell lines, murine embryonic fibroblasts
      (MEFs) and CHO cells. The total amount of beta(1) integrin was unchanged because
      LRP-1-deficient cells retained increased amounts of beta(1) in the endoplasmic
      reticulum (ER). Expression of human LRP-1 in LRP-1-deficient MEFs reversed the
      shift in subcellular beta(1) integrin distribution. Metabolic labeling
      experiments demonstrated that the precursor form of newly synthesized beta(1)
      integrin (p105) is converted into mature beta(1) (p125) more slowly in LRP-1
      deficient cells. Although low levels of cell surface beta(1) integrin, in LRP-1
      deficient MEFs, were associated with decreased adhesion to fibronectin, the
      subcellular distribution of beta(1) integrin was most profoundly dependent on LRP
      1 only after the cell cultures became confluent. A mutagen-treated CHO cell line,
      in which LRP-1 is expressed but retained in the secretory pathway, also
      demonstrated nearly complete ER retention of beta(1) integrin. These studies
      support a model in which LRP-1 either directly or indirectly promotes maturation
      of beta(1) integrin precursor and thereby increases the level of beta(1) integrin
      at the cell surface.

PMID- 14699140
TI  - Coronavirus replication complex formation utilizes components of cellular
      autophagy.
AB  - The coronavirus mouse hepatitis virus (MHV) performs RNA replication on double
      membrane vesicles (DMVs) in the cytoplasm of the host cell. However, the
      mechanism by which these DMVs form has not been determined. Using genetic,
      biochemical, and cell imaging approaches, the role of autophagy in DMV formation
      and MHV replication was investigated. The results demonstrated that replication
      complexes co-localize with the autophagy proteins, microtubule-associated protein
      light-chain 3 and Apg12. MHV infection induces autophagy by a mechanism that is
      resistant to 3-methyladenine inhibition. MHV replication is impaired in autophagy
      knockout, APG5-/-, embryonic stem cell lines, but wild-type levels of MHV
      replication are restored by expression of Apg5 in the APG5-/-cells. In MHV
      infected APG5-/-cells, DMVs were not detected; rather, the rough endoplasmic
      reticulum was dramatically swollen. The results of this study suggest that
      autophagy is required for formation of double membrane-bound MHV replication
      complexes and that DMV formation significantly enhances the efficiency of
      replication. Furthermore, the rough endoplasmic reticulum is implicated as the
      possible source of membranes for replication complexes.

PMID- 14699141
TI  - Laminar shear stress differentially modulates gene expression of p120 catenin,
      Kaiso transcription factor, and vascular endothelial cadherin in human coronary
      artery endothelial cells.
AB  - We demonstrated previously that laminar shear stress (LSS) enhances human
      coronary artery endothelial cell (HCAEC) wound closure via a vascular endothelial
      cadherin (VE-cadherin)-dependent mechanism. VE-cadherin can interact with p120
      catenin (p120(ctn)) to mediate cell locomotion and proliferation. In this study,
      we hypothesized that p120(ctn) and an interacting protein, Kaiso, a
      transcriptional factor with which p120(ctn) may interact, would be expressed
      differentially at the wound border and away from the wound border in HCAEC
      exposed to LSS. One of the major goals in this study was to assess the
      differential gene expression of p120(ctn), Kaiso, and VE-cadherin in HCAEC at
      specific locations along the wound border to further our understanding of the
      molecular mechanisms involved in wound closure. We combined the technique of
      laser capture microdissection with quantitative real time PCR to compare
      p120(ctn), Kaiso, and VE-cadherin mRNA expression in HCAEC at and away from the
      wound border under LSS. Total RNA was isolated from 200-1,000 laser-captured
      HCAEC and reverse transcribed into cDNA. Detection of p120(ctn), Kaiso, and VE
      cadherin mRNA was carried out using quantitative real time PCR. Normalization of
      cDNA templates was achieved by glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      quantification. Quantitative real time PCR analysis revealed p120(ctn):GAPDH
      ratios, Kaiso: GAPDH ratios, and VE-cadherin:GAPDH ratios, relative to static
      control for each set, of 0.99-4.18 (mean +/- S.E., 1.94 +/- 0.404), 1.0-5.24
      (2.11 +/- 0.51), and 0.99-1.42 (1.09 +/- 0.09) after 3 h of LSS, respectively.
      With these techniques, we found that p120(ctn) and Kaiso transcripts were
      increased in laser-captured HCAEC at the wound border compared with HCAEC away
      from the wound border. In addition, differential expression of p120(ctn) and
      Kaiso mRNA was observed in HCAEC depending on how LSS was applied in relation to
      the wounding process. These techniques may have wide applicability for studying
      wound healing because gene expression of key adhesion molecules in HCAEC may now
      be determined from select regions of the endothelial wound border.

PMID- 14699142
TI  - Amphetamine regulation of dopamine transport. Combined measurements of
      transporter currents and transporter imaging support the endocytosis of an active
      carrier.
AB  - Dopaminergic neurotransmission is fine-tuned by the rate of removal of dopamine
      (DA) from the extracellular space via the Na(+)/Cl(-)-dependent DA transporter
      (DAT). DAT is a target of psychostimulants such as amphetamine (AMPH) and
      cocaine. Previously, we reported that AMPH redistributes the human DAT away from
      the cell surface. This process was associated with a reduction in transport
      capacity. This loss of transport capacity may result either from a modification
      of the function of DAT that is independent of its cell surface redistribution
      and/or from a reduction in the number of active transporters at the plasma
      membrane that results from DAT trafficking. To discriminate between these
      possibilities, we stably transfected HEK-293 cells with a yellow fluorescent
      protein (YFP)-tagged human DAT (hDAT cells). In hDAT cells, acute exposure to
      AMPH induced a time-dependent loss of hDAT activity. By coupling confocal imaging
      with patch-clamp whole-cell recordings, we have demonstrated for the first time
      that the loss of AMPH-induced hDAT activity temporally parallels the accumulation
      of intracellular hDAT. In addition, presteady-state current analysis revealed a
      cocaine-sensitive, voltage-dependent capacitance current that correlated with the
      level of transporter membrane expression and in turn served to monitor the AMPH
      induced trafficking of hDAT. We found that the decrease in hDAT cell surface
      expression induced by AMPH was not paralleled by changes in the ability of the
      single transporter to carry charges. Quasi-stationary noise analysis of the AMPH
      induced hDAT currents revealed that the unitary transporter current remained
      unaltered during the loss of hDAT membrane expression. Taken together, these data
      strongly suggest that the AMPH-induced reduction of hDAT transport capacity
      results from the removal of active hDAT from the plasma membrane.

PMID- 14699143
TI  - Functional role for heat shock factors in the transcriptional regulation of human
      RANK ligand gene expression in stromal/osteoblast cells.
AB  - RANK Ligand (RANKL) is a critical osteoclastogenic factor that is expressed on
      stromal cells and osteoblasts. Most resorption stimuli induce osteoclast
      formation by modulating RANKL gene expression in marrow stromal/osteoblast cells.
      However, it is unclear how these stimuli modulate RANKL gene expression in the
      bone microenvironment. To characterize the transcriptional control of human RANKL
      gene expression in stromal/osteoblast cells, we PCR-amplified and cloned a 2-kb
      5'-flanking sequence of the RANKL gene, using normal human osteoblast derived
      genomic DNA as a template. Sequence analysis identified the presence of several
      potential Heat Shock Factor (HSF) responsive elements (HSE) in the human RANKL
      gene promoter region. Co-expression of HSF-1 or HSF-2 with the RANKL gene
      promoter-luciferase reporter plasmid in human osteoblastic cells (NOBC)
      demonstrated a 2-fold and 4.5-fold increase in promoter activity, respectively.
      RT-PCR analysis for HSF-1 and 2 mRNA expression in human bone marrow-derived
      stromal cells (SAKA-T) and osteoblast cells detected only HSF-2 expression. As
      evident from EMSA analysis, in contrast to 1,25(OH)(2)D(3) SAKA-T cells treated
      with b-FGF demonstrated increased levels of HSF-2 binding to the HSE present in
      the RANKL gene promoter region. Immunocytochemical staining further confirmed
      nuclear localization of HSF-2 in both SAKA-T transformed stromal cells and human
      bone marrow derived primary stromal/preosteoblastic cells in response to b-FGF
      treatment. Furthermore, b-FGF treatment of SAKA-T cells transfected with the
      luciferase reporter plasmid containing the hRANKL HSE region (-2 kb to -1275 bp)
      upstream to a heterologous promoter showed increased levels of transactivation.
      Western blot analysis further demonstrated enhanced levels of RANKL expression
      and HSP-27 phosphorylation in SAKA-T cells treated with b-FGF. In addition,
      overexpression of HSF-2 in SAKA-T cells resulted in a 5-fold increase in the
      levels of RANKL expression in these cells. These data further suggest that HSF-2
      is a downstream target of b-FGF to induce RANKL expression in stromal/osteoblast
      cells, and that HSF may play an important role in modulating RANKL gene
      expression in the bone microenvironment.

PMID- 14699144
TI  - Receptor trafficking via the perinuclear recycling compartment accompanied by
      cell division is necessary for permanent neurotensin cell sensitization and leads
      to chronic mitogen-activated protein kinase activation.
AB  - Most G protein-coupled receptors are internalized after interaction with their
      respective ligand, a process that subsequently contributes to cell
      desensitization, receptor endocytosis, trafficking, and finally cell
      resensitization. Although cellular mechanisms leading to cell desensitization
      have been widely studied, those responsible for cell resensitization are still
      poorly understood. We examined here the traffic of the high affinity neurotensin
      receptor (NT1 receptor) following prolonged exposure to high agonist
      concentration. Fluorescence and confocal microscopy of Chinese hamster ovary,
      human neuroblastoma (CHP 212), and murine neuroblastoma (N1E-115) cells
      expressing green fluorescent protein-tagged NT1 receptor revealed that under
      prolonged treatment with saturating concentrations of neurotensin (NT) agonist,
      NT1 receptor and NT transiently accumulated in the perinuclear recycling
      compartment (PNRC). During this cellular event, cell surface receptors remained
      markedly depleted as detected by both confocal microscopy and (125)I-NT binding
      assays. In dividing cells, we observed that following prolonged NT agonist
      stimulation, NT1 receptors were removed from the PNRC, accumulated in dispersed
      vesicles inside the cytoplasm, and subsequently reappeared at the cell surface.
      This NT binding recovery allowed for constant cell sensitization and led to a
      chronic activation of mitogen-activated protein kinases p42 and p44. Under these
      conditions, the constant activation of NT1 receptor generates an oncogenic
      regulation. These observations support the potent role for neuropeptides, such as
      NT, in cancer progression.

PMID- 14699145
TI  - Phospholipids can switch the GTPase substrate preference of a GTPase-activating
      protein.
AB  - The major cellular inhibitors of the small GTPases of the Ras superfamily are the
      GTPase-activating proteins (GAPs), which stimulate the intrinsic GTP hydrolyzing
      activity of GTPases, thereby inactivating them. The catalytic activity of several
      GAPs is reportedly inhibited or stimulated by various phospholipids and fatty
      acids in vitro, indicating a likely physiological role for lipids in regulating
      small GTPases. We find that the p190 RhoGAP, a potent GAP for the Rho and Rac
      GTPases, is similarly sensitive to phospholipids. Interestingly, however, several
      of the tested phospholipids were found to effectively inhibit the RhoGAP activity
      of p190 but stimulate its RacGAP activity. Thus, phospholipids have the ability
      to "switch" the GTPase substrate preference of a GAP, thereby providing a novel
      regulatory mechanism for the small GTPases.

PMID- 14699146
TI  - SOCS3 is a physiological negative regulator for granulopoiesis and granulocyte
      colony-stimulating factor receptor signaling.
AB  - The suppressor of cytokine signaling-3 (SOCS3/CIS3) has been shown to be an
      important negative regulator of cytokines, especially cytokines that activate
      STAT3. To examine the role of SOCS3 in neutrophils and the granulocyte colony
      stimulating factor (G-CSF) signaling in vivo, we compared neutrophils from two
      types of conditional knockout mice, LysM-Cre:SOCS3(fl/fl) mice and Tie2
      Cre:SOCS3(fl/fl) mice, in which the Socs3 gene had been deleted in mature
      neutrophils and hematopoietic stem cells, respectively. The size of the G-CSF
      dependent colonies from Tie2-Cre:SOCS3(fl/fl) mouse bone marrow was much larger
      than that of colonies from control wild-type mice, while the size of interleukin
      3-dependent colonies was similar. Moreover, LysM-Cre:SOCS3(fl/fl) mice had more
      neutrophils than SOCS3(fl/fl) mice, suggesting that SOCS3 is a negative regulator
      of G-CSF signaling in neutrophils. Consistent with this notion, G-CSF-induced
      STAT3 as well as mitogen-activated protein kinase activation was much stronger
      and prolonged in SOCS3-deficient mature neutrophils than in wild-type
      neutrophils. The preventive effect of G-CSF on apoptosis was more prominent in
      SOCS3-deficient mature neutrophils than in control neutrophils. These data
      indicate that SOCS3 negatively regulates granulopoiesis and G-CSF signaling in
      neutrophils and may contribute to neutrophilia or neutropenia.

PMID- 14699147
TI  - Engineered human IgG antibodies with longer serum half-lives in primates.
AB  - The neonatal Fc receptor (FcRn) plays an important role in regulating the serum
      half-lives of IgG antibodies. A correlation has been established between the pH
      dependent binding affinity of IgG antibodies to FcRn and their serum half-lives
      in mice. In this study, molecular modeling was used to identify Fc positions near
      the FcRn binding site in a human IgG antibody that, when mutated, might alter the
      binding affinity of IgG to FcRn. Following mutagenesis, several IgG2 mutants with
      increased binding affinity to human FcRn at pH 6.0 were identified at Fc
      positions 250 and 428. These mutants do not bind to human FcRn at pH 7.5. A
      pharmacokinetics study of two mutant IgG2 antibodies with increased FcRn binding
      affinity indicated that they had serum half-lives in rhesus monkeys approximately
      2-fold longer than the wild-type antibody.

PMID- 14699148
TI  - Poly(ADP-ribose) reactivates stalled DNA topoisomerase I and Induces DNA strand
      break resealing.
AB  - Regulating the topological state of DNA is a vital function of the enzyme DNA
      topoisomerase I. However, when acting on damaged DNA, topoisomerase I may get
      trapped in a covalent complex with nicked DNA (stalled topoisomerase I), that, if
      unrepaired, may lead to genomic instability or cell death. Here we show that ADP
      ribose polymers target specific domains of topoisomerase I and reprogram the
      enzyme to remove itself from cleaved DNA and close the resulting gap. Two members
      of the poly(ADP-ribose) polymerase family, PARP-1 and 2, act as poly(ADP-ribose)
      carriers to stalled topoisomerase I sites and induce efficient repair of enzyme
      associated DNA strand breaks. Thus, by counteracting topoisomerase I-induced DNA
      damage, PARP-1 and PARP-2 act as positive regulators of genomic stability in
      eukaryotic cells.

PMID- 14699149
TI  - The cavity structure for docking the K(+)-competitive inhibitors in the gastric
      proton pump.
AB  - 2-Methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile (SCH 28080) is a
      reversible inhibitor specific for the gastric proton pump. The inhibition pattern
      is competitive with K(+). Here we studied the binding sites of this inhibitor on
      the putative three-dimensional structure of the gastric proton pump alpha-subunit
      that was constructed by homology modeling based on the structure of sarcoplasmic
      reticulum Ca(2+) pump. Alanine and serine mutants of Tyr(801) located in the
      fifth transmembrane segment of the gastric proton pump alpha-subunit retained the
      (86)Rb transport and K(+)-dependent ATPase (K(+)-ATPase) activities. These
      mutants showed 60-80-times lower sensitivity to SCH 28080 than the wild type in
      the (86)Rb transport activity. The K(+)-ATPase activities of these mutants were
      not completely inhibited by SCH 28080. The sensitivity to SCH 28080 was dependent
      on the bulkiness of the side chain at this position. Therefore, the side chain of
      Tyr(801) is important for the interaction with this inhibitor. In the three
      dimensional structure of the E(2) form (conformation with high affinity for K(+))
      of the gastric proton pump, Tyr(801) faces a cavity surrounded by the first,
      fourth, fifth, sixth, and eighth transmembrane segments and fifth/sixth,
      seventh/eighth, and ninth/tenth loops. SCH 28080 can dock in this cavity.
      However, SCH 28080 cannot dock in the same location in the E(1) form
      (conformation with high affinity for proton) of the gastric proton pump due to
      the drastic rearrangement of the transmembrane helices between the E(1) and E(2)
      forms. These results support the idea that this cavity is the binding pocket of
      SCH 28080.

PMID- 14699151
TI  - Interaction of bcl-2 with Paxillin through its BH4 domain is important during
      ureteric bud branching.
AB  - bcl-2 protects cells from apoptosis initiated by a variety of stimuli including
      loss of cell adhesion. Mice deficient in bcl-2 (bcl-2-/-) develop renal
      hypoplastic/cystic dysplasia, a condition that leads to significant morbidity and
      mortality in children. The precise mechanism of action of bcl-2 has not been
      elucidated. bcl-2 may merely facilitate survival of precursor cells and/or may
      play a more "active" role during morphogenesis by interacting with other proteins
      such as paxillin. Recent work in this laboratory demonstrated that bcl-2 directly
      associates with paxillin. The data presented here demonstrate that the bcl-2
      homology 4 (BH4) domain, specifically amino acids 17-31, is necessary for the bcl
      2 interaction with paxillin. Paxillin also associated with the BH4 domains of
      more closely related bcl-2 family members, bcl-xL and bcl-w, compared with that
      from the non-mammalian homologue ced9. Tyrosines 21 and 28 in the bcl-2 BH4
      domain were essential for interaction with paxillin. In embryonic kidney organ
      culture, incubation with the bcl-2 BH4 domain resulted in inhibition of ureteric
      bud branching. Therefore, these data suggest that the interaction of bcl-2 with
      paxillin plays an important role during nephrogenesis.

PMID- 14699150
TI  - Accelerated cell cycle progression in osteoblasts overexpressing the c-fos proto
      oncogene: induction of cyclin A and enhanced CDK2 activity.
AB  - Transgenic mice overexpressing the c-Fos oncoprotein develop osteosarcomas that
      are associated with deregulated expression of cell cycle genes. Here we have
      generated osteoblast cell lines expressing c-fos under the control of a
      tetracycline-regulatable promoter to investigate the role of c-Fos in osteoblast
      cell cycle control in vitro. Three stable subclones, AT9.2, AT9.3, and AT9.7,
      derived from MC3T3-E1 mouse osteoblasts, expressed high levels of exogenous c-fos
      mRNA and protein in the absence of tetracycline. Functional contribution of
      ectopic c-Fos to AP-1 complexes was confirmed by electromobility shift assays and
      transactivation of AP-1 reporter constructs. Induction of exogenous c-Fos in
      quiescent AT9.2 cells caused accelerated S-phase entry following serum
      stimulation, resulting in enhanced growth rate. Ectopic c-Fos resulted in
      increased expression of cyclins A and E protein levels, and premature activation
      of cyclin A-, cyclin E-, and cyclin-dependent kinase (CDK) 2-associated kinase
      activities, although cyclin D levels and CDK4 activity were not affected
      significantly in these cell lines. The enhanced CDK2 kinase activity was
      associated with a rapid, concomitant dissociation of p27 from CDK2-containing
      complexes. Deregulated cyclin A expression and CDK2 activity was also observed in
      primary mouse osteoblasts overexpressing c-Fos, but not in fibroblasts, and c-Fos
      transgenic tumor-derived osteosarcoma cells constitutively expressed high levels
      of cyclin A protein. These data suggest that overexpression of c-Fos in
      osteoblasts results in accelerated S phase entry as a result of deregulated
      cyclin A/E-CDK2 activity. This represents a novel role for c-Fos in osteoblast
      growth control and may provide c-Fos-overexpressing osteoblasts with a growth
      advantage during tumorigenesis.

PMID- 14699152
TI  - Pleckstrin homology domain diffusion in Dictyostelium cytoplasm studied using
      fluorescence correlation spectroscopy.
AB  - The translocation of pleckstrin homology (PH) domain-containing proteins from the
      cytoplasm to the plasma membrane plays an important role in the chemotaxis
      mechanism of Dictyostelium cells. The diffusion of three PH domain-green
      fluorescent protein (GFP) fusions (PH2-GFP, PH10-GFP, and PH-CRAC (cytosolic
      regulator of adenylyl cyclase)-GFP) in the cytoplasm of vegetative and
      chemotaxing Dictyostelium cells has been studied using fluorescence correlation
      spectroscopy to gain a better understanding of the functioning of the domains and
      to assess the effect of initiation of chemotaxis on these domains in the cell.
      PH2-GFP was homogeneously distributed in vegetative as well as chemotaxing cells,
      whereas PH10-GFP and PH-CRAC-GFP showed translocation to the leading edge of the
      chemotaxing cell. The diffusion characteristics of PH2-GFP and PH-CRAC-GFP were
      very similar; however, PH10-GFP exhibited slower diffusion. Photon counting
      histogram statistics show that this slow diffusion was not due to aggregation.
      Diffusion of the three PH domains was affected to similar extents by
      intracellular heterogeneities in vegetative as well as chemotaxing cells. From
      the diffusion of free cytoplasmic GFP, it was calculated that the viscosity in
      chemotaxing cells was 1.7 times lower than in vegetative cells. In chemotaxing
      cells, PH2-GFP showed increased mobility, whereas the mobilities of PH10-GFP and
      PH-CRAC-GFP remained unchanged.

PMID- 14699153
TI  - Cleavage of amyloid-beta precursor protein and amyloid-beta precursor-like
      protein by BACE 1.
AB  - Site-specific proteolysis of the amyloid-beta precursor protein (APP) by BACE 1
      and gamma-secretase, a central event in Alzheimer disease, releases a large
      secreted extracellular fragment (called APP(S)), peptides of 40-43 residues
      derived from extracellular and transmembrane sequences (Abeta), and a short
      intracellular fragment (APP intracellular domain) that may function as a
      transcriptional activator in a complex with the adaptor protein Fe65 and the
      nuclear protein Tip60. APP is closely related to APP-like protein (APLP) 1 and
      APLP2, but only APP is known to be cleaved by BACE 1 and to be involved in
      Alzheimer disease. We now demonstrate that similar to APP, APLP1 and APLP2 are
      also cleaved by BACE 1 but not by ADAM 9, another APP protease, and also
      transactivate nuclear Tip60 in a complex with Fe65. Paradoxically, although BACE
      1 cleavage appears to be specific for APP and APLPs, their cleavage sequences
      exhibit no homology, and a short sequence (7 amino acids) from APP that when
      placed close to the membrane converts a membrane protein that is normally not
      cleaved by BACE 1 into a BACE 1 substrate. Our data demonstrate that APLPs and
      APP are processed similarly to act via the same nuclear target, suggesting that
      BACE 1 cleavage regulates a common function of APP and APLPs in neurons.

PMID- 14699154
TI  - Ceramide selectively displaces cholesterol from ordered lipid domains (rafts):
      implications for lipid raft structure and function.
AB  - Ceramide is a membrane lipid involved in a number of crucial biological
      processes. Recent evidence suggests that ceramide is likely to reside and
      function within lipid rafts; ordered sphingolipid and cholesterol-rich lipid
      domains believed to exist within many eukaryotic cell membranes. Using lipid
      vesicles containing co-existing raft domains and disordered fluid domains, we
      find that natural and saturated synthetic ceramides displace sterols from rafts.
      Other raft lipids remain raft-associated in the presence of ceramide, showing
      displacement is relatively specific for sterols. Like cholesterol-containing
      rafts, ceramide-rich "rafts" remain in a highly ordered state. Comparison of the
      sterol-displacing abilities of natural ceramides with those of saturated
      diglycerides and an unsaturated ceramide demonstrates that tight lipid packing is
      critical for sterol displacement by ceramide. Based on these results, and the
      fact that cholesterol and ceramides both have small polar headgroups, we propose
      that ceramides and cholesterol compete for association with rafts because of a
      limited capacity of raft lipids with large headgroups to accommodate small
      headgroup lipids in a manner that prevents unfavorable contact between the
      hydrocarbon groups of the small headgroup lipids and the surrounding aqueous
      environment. Minimizing the exposure of cholesterol and ceramide to water may be
      a strong driving force for the association of other molecules with rafts.
      Furthermore, displacement of sterol from rafts by ceramide is very likely to have
      marked effects upon raft structure and function, altering liquid ordered
      properties as well as molecular composition. In this regard, certain previously
      observed physiological processes may be a result of displacement. In particular,
      a direct connection to the previously observed sphingomyelinase-induced
      displacement of cholesterol from plasma membranes in cells is proposed.

PMID- 14699155
TI  - Lipopolysaccharide-induced c-Jun NH2-terminal kinase activation in human
      neutrophils: role of phosphatidylinositol 3-Kinase and Syk-mediated pathways.
AB  - Polymorphonuclear leukocytes (neutrophils) respond to lipopolysaccharide (LPS)
      through the up-regulation of several pro-inflammatory mediators. We have recently
      shown that LPS-stimulated neutrophils express monocyte chemoattractant protein 1
      (MCP-1), an AP-1-dependent gene, suggesting that LPS activates the c-Jun N
      terminal kinase (JNK) pathway in neutrophils. Previously, we have shown the
      activation of p38 MAPK, but not JNK, in suspended neutrophils stimulated with LPS
      but have recently shown activation of JNK by TNF-alpha in an adherent neutrophil
      system. We show here that exposure to LPS activates JNK in non-suspended
      neutrophils and that LPS-induced MCP-1 expression, but not tumor necrosis factor
      alpha (TNF-alpha) or interleukin-8 (IL-8), is dependent on JNK activation. In
      addition, LPS stimulation of non-suspended neutrophils activates Syk and
      phosphatidylinositol 3-kinase (PI3K). Inhibition of Syk with piceatannol or PI3K
      with wortmannin inhibited LPS-induced JNK activation and decreased MCP-1
      expression after exposure to LPS, suggesting that both Syk and PI3K reside in a
      signaling pathway leading to LPS-induced JNK activation in neutrophils. This Syk-
      and PI3K-dependent pathway leading to JNK activation after LPS exposure in non
      suspended neutrophils is specific for JNK, because inhibition of neither Syk nor
      PI3K decreased p38 activation after LPS stimulation. Furthermore we show that
      PI3K inhibition decreased LPS-induced Syk activation suggesting that PI3K resides
      upstream of Syk in this pathway. Finally, we show that Syk associates with Toll
      like receptor 4 (TLR4) upon LPS stimulation further implicating Syk in the LPS
      induced signaling pathway in neutrophils. Overall our data suggests that LPS
      induces JNK activation only in non-suspended neutrophils, which proceeds through
      Syk- and PI3K-dependent pathways, and that JNK activation is important for LPS
      induced MCP-1 expression but not for TNF-alpha or IL-8 expression.

PMID- 14699156
TI  - Participation of p97Eps8 in Src-mediated transformation.
AB  - Histone acetylase and histone deacetylase are two crucial enzymes that determine
      the structure of chromatin, regulating gene expression. In this study, we
      observed that trichostatin A (TSA), a specific histone deacetylase inhibitor,
      could effectively inhibit the growth of v-Src-transformed (IV5) cells and
      abrogate their ability to form colonies in soft agar. Further analysis
      demonstrated that, although TSA reduced the expression of Eps8 in a dose- and
      time-dependent manner, both the protein expression and kinase activity of v-Src
      remained constant, and the abundance and phosphotyrosine levels of Src
      substrates, including cortactin, focal adhesion kinase, p130(Cas), paxillin, and
      Shc, were not altered. Notably, removal of TSA from the medium restored not only
      the expression of Eps8, but also cellular growth. Northern and reverse
      transcription-PCR analyses revealed the significant reduction of eps8 transcripts
      in TSA-treated IV5 cells relative to control cells. When active Src-expressing
      chicken embryonic cells were forced to overexpress p97(Eps8), they became
      resistant to TSA-mediated anti-proliferation. Furthermore, using small
      interference RNA of eps8, we demonstrated the requirement for Eps8 in IV5 cell
      proliferation. Thus, our results highlight a critical role for p97(Eps8) in TSA
      exerted growth inhibition of v-Src-transformed cells.

PMID- 14699157
TI  - Human homolog of disc-large is required for adherens junction assembly and
      differentiation of human intestinal epithelial cells.
AB  - We and others have shown that phosphatidylinositol 3-kinase (PI3K) is recruited
      to and activated by E-cadherin engagement. This PI3K activation is essential for
      adherens junction integrity and intestinal epithelial cell differentiation. Here
      we provide evidence that hDlg, the homolog of disc-large tumor suppressor, is
      another key regulator of adherens junction integrity and differentiation in
      mammalian epithelial cells. We report the following. 1) hDlg co-localizes with E
      cadherin, but not with ZO-1, at the sites of cell-cell contact in intestinal
      epithelial cells. 2) Reduction of hDlg expression levels by RNA(i) in intestinal
      cells not only severely alters adherens junction integrity but also prevents the
      recruitment of p85/PI3K to E-cadherin-mediated cell-cell contact and inhibits
      sucrase-isomaltase gene expression. 3) PI3K and hDlg are associated with E
      cadherin in a common macromolecular complex in living differentiating intestinal
      cells. 4) This interaction requires the association of hDlg with E-cadherin and
      with Src homology domain 2 domains of the p85/PI3K subunit. 5) Phosphorylation of
      hDlg on serine and threonine residues prevents its interaction with the p85 Src
      homology domain 2 in subconfluent cells, whereas phosphorylation of hDlg on
      tyrosine residues is essential. We conclude that hDlg may be a determinant in E
      cadherin-mediated adhesion and signaling in mammalian epithelial cells.

PMID- 14699158
TI  - A recA-LexA-dependent pathway mediates ciprofloxacin-induced fibronectin binding
      in Staphylococcus aureus.
AB  - Subinhibitory concentrations of ciprofloxacin (CPX) raise the fibronectin
      mediated attachment of fluoroquinolone-resistant Staphylococcus aureus by
      selectively inducing fnbB coding for one of two fibronectin-binding proteins:
      FnBPB. To identify candidate regulatory pathway(s) linking drug exposure to up
      regulation of fnbB, we disrupted the global response regulators agr, sarA, and
      recA in the highly quinolone-resistant strain RA1. Whereas agr and sarA mutants
      of RA1 exposed to CPX still displayed increased adhesion to fibronectin, the CPX
      triggered response was abolished in the uvs-568 recA mutant, but was restored
      following complementation with wild type recA. Steady-state levels of recA and
      fnbB, but not fnbA, mRNA were co-coordinately increased >3-fold in CPX-exposed
      strain RA1. Electrophoretic mobility shift assays revealed specific binding of
      purified S. aureus SOS-repressor LexA to recA and fnbB, but not to fnbA or rpoB
      promoters. DNase I footprint analysis showed LexA binding overlapping the core
      promoter elements in fnbB. We conclude that activation of recA and derepression
      of lexA-regulated genes by CPX may represent a response to drug-induced damage
      that results in a novel induction of a virulence factor leading to increased
      bacterial tissue adherence.

PMID- 14699159
TI  - Underglycosylation of ATF6 as a novel sensing mechanism for activation of the
      unfolded protein response.
AB  - ATF6 is a key transcriptional activator of the unfolded protein response (UPR),
      which allows mammalian cells to maintain cellular homeostasis when they are
      subjected to a variety of environmental and physiological stresses that target
      the endoplasmic reticulum (ER). ATF6, a 90-kDa ER transmembrane protein, contains
      three evolutionarily conserved N-linked glycosylation sites within its carboxyl
      luminal domain. Although it is well established that p90ATF6 activation requires
      transit from the ER to the Golgi, where it is cleaved by the S1P/S2P protease
      system to generate a nuclear form p60ATF6 that acts as a transcriptional
      activator, the functional significance of p90ATF6 N-linked glycosylation is
      unknown. Here we show that ER Ca(2+) depletion stress, a triggering mechanism for
      the UPR, induces the formation of ATF6(f), which represents de novo partial
      glycosylation of newly synthesized p90ATF6. By mutating a single amino acid
      within the N-linked glycosylation site closest to the carboxyl terminus of
      p90ATF6, we recreated ATF6(f). This mutation sharply reduces p90ATF6 association
      with calreticulin, a major Ca(2+)-binding chaperone for N-glycoprotein. We
      further determined that ATF6(f) exhibits a faster rate of constitutive transport
      to the Golgi, resulting in a higher level of p60ATF6 in the nucleus and stronger
      transactivating activity in the absence of ER stress. Additional analysis of
      p90ATF6 mutants targeting single or multiple N-glycosylation sites also showed
      higher constitutive transactivating activity than wild type ATF6. Because
      accumulation of underglycosylated proteins in the ER is a potent inducer for the
      UPR, these studies uncover a novel mechanism whereby the glycosylation status of
      p90ATF6 can serve as a sensor for ER homeostasis, resulting in ATF6 activation to
      trigger the UPR.

PMID- 14699160
TI  - Activation and localization of inositol phosphosphingolipid phospholipase C,
      Isc1p, to the mitochondria during growth of Saccharomyces cerevisiae.
AB  - Sphingomyelinases (SMases) generate ceramides, which are known to regulate cell
      cycle and growth. Only one enzyme that belongs to the extended family of SMases
      is present in S. cerevisiae, Isc1p; however, little is known about its regulation
      or physiologic function. Deletion of ISC1 in S. cerevisiae resulted in a growth
      defect, and the slow growth phenotype was rescued by plasmid-borne expression of
      Isc1, confirming its role in growth. The levels of phytoceramide exhibited an
      Isc1p-dependent increase of approximately 4-fold after 24 h of growth. In
      addition, the specific activity of Isc1p was significantly elevated (>3-fold)
      between the early logarithmic and the late logarithmic/start of stationary phases
      of growth. The activation of the enzyme was not associated with increased levels
      of the protein, indicating that the mechanism is independent of
      transcription/translation. Interestingly, this activation was lost upon
      delipidation of the enzyme, raising the possibility of regulation by associated
      lipids. Confocal microscopy revealed that the enzyme was predominantly in the ER
      during early growth but became associated with mitochondria in late logarithmic
      growth. These results were also supported by differential centrifugation and
      isolation of mitochondria and further confirmed in mitochondria purified using
      sucrose gradients at the different stages of growth. These results reveal that
      the activity and localization of Isc1p are regulated in a growth-dependent
      manner. A novel mechanism for activation of Isc1p through localization to
      mitochondria is proposed. The results also suggest a role for Isc1p-generated
      ceramides in optimal regulation of growth.

PMID- 14699161
TI  - Pro-nucleotide inhibitors of adenylyl cyclases in intact cells.
AB  - 9-substituted adenine derivatives with protected phosphoryl groups were
      synthesized and tested as inhibitors of adenylyl cyclase in isolated enzyme and
      intact cell systems. Protected 3'-phosphoryl derivatives of 2',5'
      dideoxyadenosine (2',5'-dd-Ado) and beta-l-2',5'-dd-Ado, protected 5'-phosphoryl
      derivatives of beta-l-2',3'-dd-Ado, and protected phosphoryl derivatives of two 9
      (2-phosphonomethoxy-acyl)-adenines were synthesized. Protection was afforded by
      two cyclosaligenyl- or three S-acyl-2-thioethyl-substituents. These pro
      nucleotides were tested for their capacity to block forskolin-induced increases
      in [(3)H]cAMP in OB1771 and F442A preadipocytes and human macrophages prelabeled
      with [(3)H]adenine. A striking selectivity for 2',5'-dd-Ado-3'-phosphoryl
      derivatives was observed. Cyclosaligenyl-derivatives (IC(50) approximately 2
      microm) were much less potent than S-acyl-2-thioethyl-derivatives. Best studied
      of these was 2',5'-dd-Ado-3'-O-bis(S-pivaloyl-2-thioethyl)-phosphate, which
      blocked [(3)H]cAMP formation in preadipocytes (IC(50) approximately 30 nm) and
      suppressed opening of cAMP-dependent Cl(-) channels in cardiac myocytes (IC(50)
      approximately 800 nm). None of the pro-nucleotides inhibited adenylyl cyclase per
      se, whether isolated from rat brain or OB1771 cells. These compounds exhibit the
      hallmarks of prodrugs. Data suggest they are taken up, are deprotected, and are
      converted to a potent inhibitory form to inhibit adenylyl cyclase, but only by
      intact cells. The availability and characteristics of these prodrugs should make
      them useful for blocking cAMP-mediated pathways in intact cell systems, in
      biochemical, pharmacological, and potentially therapeutic contexts.

PMID- 14699162
TI  - Munc13-4 is a GTP-Rab27-binding protein regulating dense core granule secretion
      in platelets.
AB  - Platelets store self-agonists such as ADP and serotonin in dense core granules.
      Although exocytosis of these granules is crucial for hemostasis and thrombosis,
      the underlying mechanism is not fully understood. Here, we show that incubation
      of permeabilized platelets with unprenylated active mutant Rab27A-Q78L, wild type
      Rab27A, and Rab27B inhibited the secretion, whereas inactive mutant Rab27A-T23N
      and other GTPases had no effects. Furthermore, we affinity-purified a GTP-Rab27A
      binding protein in platelets and identified it as Munc13-4, a homologue of Munc13
      1 known as a priming factor for neurotransmitter release. Recombinant Munc13-4
      directly bound to GTP-Rab27A and -Rab27B in vitro, but not other GTPases, and
      enhanced secretion in an in vitro assay. The inhibition of secretion by
      unprenylated Rab27A was rescued by the addition of Munc13-4, suggesting that
      Munc13-4 mediates the function of GTP-Rab27. Thus, Rab27 regulates the dense core
      granule secretion in platelets by employing its binding protein, Munc13-4.

PMID- 14699163
TI  - Stopped-flow fluorescence studies of inhibitor binding to tyrosinase from
      Streptomyces antibioticus.
AB  - Tyrosinase (Ty) is a type 3 copper protein involved in the rate-limiting step of
      melanin synthesis. It is shown that the endogenous Trp fluorescence of tyrosinase
      from Streptomyces antibioticus is remarkably sensitive to the redox state. The
      fluorescence emission intensity of the [(Cu(I) Cu(I)] reduced species is more
      than twice that of the oxygen-bound [Cu(II)-O(2)(2-)-Cu(II)] form. The emission
      intensity of the oxidized [Cu(II)-OH(-)-Cu(II)] protein (Ty(met)) appears to be
      dependent on an acid-base equilibrium with a pK(a) value of 4.5 +/- 0.1. The
      binding of fluoride was studied under pseudo first-order conditions using stopped
      flow fluorescence spectroscopy. The kinetic parameters k(on), K(d), and the
      fraction of fluorescence emission quenched upon fluoride binding show a similar
      pH dependence as above with an average pK(a) value of 4.62 +/- 0.05. Both
      observations are related to the dissociation of Cu(2)-bridging hydroxide at low
      pH. It is further shown that Ty is rapidly inactivated at low pH and that halide
      protects the enzyme from this inactivation. All results support the hypothesis
      that halide displaces hydroxide as the Cu(2)-bridging ligand in Ty(met). The
      relevance of the experimental findings for the catalytic cycle is discussed. The
      data are consistent with the data obtained from other techniques, validating the
      use of fluorescence quenching as a sensitive and effective tool in studying
      ligand binding and substrate conversion.

PMID- 14699165
TI  - Dentin matrix protein 1 immobilized on type I collagen fibrils facilitates
      apatite deposition in vitro.
AB  - During bone and dentin mineralization, the crystal nucleation and growth
      processes are considered to be matrix regulated. Osteoblasts and odontoblasts
      synthesize a polymeric collagenous matrix, which forms a template for apatite
      initiation and elongation. Coordinated and controlled reaction between type I
      collagen and bone/dentin-specific noncollagenous proteins are necessary for well
      defined biogenic crystal formation. However, the process by which collagen
      surfaces become mineralized is not understood. Dentin matrix protein 1 (DMP1) is
      an acidic noncollagenous protein expressed during the initial stages of
      mineralized matrix formation in bone and dentin. Here we show that DMP1 bound
      specifically to type I collagen, with the binding region located at the N
      telopeptide region of type I collagen. Peptide mapping identified two acidic
      clusters in DMP1 responsible for interacting with type I collagen. The collagen
      binding property of these domains was further confirmed by site-directed
      mutagenesis. Transmission electron microscopy analyses have localized DMP1 in the
      gap region of the collagen fibrils. Fibrillogenesis assays further demonstrated
      that DMP1 accelerated the assembly of the collagen fibrils in vitro and also
      increased the diameter of the reconstituted collagen fibrils. In vitro
      mineralization studies in the presence of calcium and phosphate ions demonstrated
      apatite deposition only at the collagen-bound DMP1 sites. Thus specific binding
      of DMP1 and possibly other noncollagenous proteins on the collagen fibril might
      be a key step in collagen matrix organization and mineralization.

PMID- 14699164
TI  - The Ddx20/DP103 dead box protein represses transcriptional activation by
      Egr2/Krox-20.
AB  - The early growth response 2 (Egr2/Krox-20) transcription factor is essential for
      myelination of the peripheral nervous system and segmentation of the vertebrate
      hindbrain. To probe the mechanism by which Egr2 is regulated, we used a yeast two
      hybrid assay and identified an RNA helicase, Ddx20 (DP103/Gemin3), as an Egr2
      interacting protein. Mammalian two-hybrid assays indicated that Ddx20 can
      interact with Egr1, Egr3, and Egr4, in addition to Egr2, making it the only known
      cofactor that interacts with all four Egr family members. Using several Egr2
      target promoters, we found that Ddx20 repressed Egr2-mediated transcriptional
      activation with significant promoter specificity. In addition, Ddx20 repressed
      Egr2-mediated activation of the endogenous insulin-like growth factor 2 (IGF2)
      gene. Interestingly, the C-terminal segment of Ddx20, which lacks the DEAD box
      helicase domain, was sufficient for its robust and specific repression. We also
      examined possible interactions between Ddx20 and Nab proteins, the only other
      known corepressors of the Egr family, and found that these two corepressors act
      independently. Finally, transcriptional repression assays performed in the
      presence of a histone deacetylase inhibitor (trichostatin A) indicate that
      although repression of certain promoters by Ddx20 requires histone deacetylase
      activity, another repression mechanism must also be involved. Because Egr2 is
      critical for hindbrain development and peripheral nerve myelination, modulation
      of Egr2 by Ddx20 may play an important role in maintaining the correct expression
      level of Egr2 target genes.

PMID- 14699166
TI  - Effective dephosphorylation of Src substrates by SHP-1.
AB  - The protein-tyrosine phosphatase SHP-1 is a negative regulator of multiple signal
      transduction pathways. We observed that SHP-1 effectively antagonized Src
      dependent phosphorylations in HEK293 cells. This occurred by dephosphorylation of
      Src substrates, because Src activity was unaffected in the presence of SHP-1. One
      reason for efficient dephosphorylation was activation of SHP-1 by Src.
      Recombinant SHP-1 had elevated activity subsequent to phosphorylation by Src in
      vitro, and SHP-1 variants with mutated phosphorylation sites in the C terminus,
      SHP-1 Y538F, and SHP-1 Y538F,Y566F were less active toward Src-generated
      phosphoproteins in intact cells. A second reason for efficient dephosphorylation
      is the substrate selectivity of SHP-1. Pull-down experiments with different GST
      SHP-1 fusion proteins revealed efficient interaction of Src-generated
      phosphoproteins with the SHP-1 catalytic domain rather than with the SH2 domains.
      Phosphopeptides that correspond to good Src substrates were efficiently
      dephosphorylated by SHP-1 in vitro. Phosphorylated "optimal Src substrate"
      AEEEIpYGEFEA (where pY is phosphotyrosine) and a phosphopeptide corresponding to
      a recently identified Src phosphorylation site in p120 catenin, DDLDpY(296)GMMSD,
      were excellent SHP-1 substrates. Docking of these phosphopeptides into the
      catalytic domain of SHP-1 by molecular modeling was consistent with the
      biochemical data and explains the efficient interaction. Acidic residues N
      terminal of the phosphotyrosine seem to be of major importance for efficient
      substrate interaction. Residues C-terminal of the phosphotyrosine probably
      contribute to the substrate selectivity of SHP-1. We propose that activation of
      SHP-1 by Src and complementary substrate specificities of SHP-1 and Src may lead
      to very transient Src signals in the presence of SHP-1.

PMID- 14699167
TI  - Modulation of [Ca2+]i signaling dynamics and metabolism by perinuclear
      mitochondria in mouse parotid acinar cells.
AB  - Parotid acinar cells exhibit rapid cytosolic calcium signals ([Ca2+]i) that
      initiate in the apical region but rapidly become global in nature. These
      characteristic [Ca2+]i signals are important for effective fluid secretion, which
      critically depends on a synchronized activation of spatially separated ion
      fluxes. Apically restricted [Ca2+]i signals were never observed in parotid acinar
      cells. This is in marked contrast to the related pancreatic acinar cells, where
      the distribution of mitochondria has been suggested to contribute to restricting
      [Ca2+]i signals to the apical region. Therefore, the aim of this study was to
      determine the mitochondrial distribution and the role of mitochondrial Ca2+
      uptake in shaping the spatial and temporal properties of [Ca2+]i signaling in
      parotid acinar cells. Confocal imaging of cells stained with MitoTracker dyes
      (MitoTracker Green FM or MitoTracker CMXRos) and SYTO dyes (SYTO-16 and SYTO-61)
      revealed that a majority of mitochondria is localized around the nucleus.
      Carbachol (CCh) and caged inositol 1,4,5-trisphosphate-evoked [Ca2+]i signals
      were delayed as they propagated through the nucleus. This delay in the CCh-evoked
      nuclear [Ca2+]i signal was abolished by inhibition of mitochondrial Ca2+ uptake
      with ruthenium red and Ru360. Likewise, simultaneous measurement of [Ca2+]i with
      mitochondrial [Ca2+] ([Ca2+]m), using fura-2 and rhod-FF, respectively, revealed
      that mitochondrial Ca2+ uptake was also inhibited by ruthenium red and Ru360.
      Finally, at concentrations of agonist that evoke[Ca2+]i oscillations,
      mitochondrial Ca2+ uptake, and a nuclear [Ca2+] delay, CCh also evoked a
      substantial increase in NADH autofluorescence. This autofluorescence exhibited a
      predominant perinuclear localization that was also sensitive to mitochondrial
      inhibitors. These data provide evidence that perinuclear mitochondria and
      mitochondrial Ca2+ uptake may differentially shape nuclear [Ca2+] signals but
      more importantly drive mitochondrial metabolism to generate ATP close to the
      nucleus. These effects may profoundly affect a variety of nuclear processes in
      parotid acinar cells while facilitating efficient fluid secretion.

PMID- 14699168
TI  - ATP binding at human P2X1 receptors. Contribution of aromatic and basic amino
      acids revealed using mutagenesis and partial agonists.
AB  - P2X receptors comprise a family of ATP-gated ion channels with the basic amino
      acids Lys-68, Arg-292, and Lys-309 (P2X(1) receptor numbering) contributing to
      agonist potency. In many ATP-binding proteins aromatic amino acids coordinate the
      binding of the adenine group. There are 20 conserved aromatic amino acids in the
      extracellular ligand binding loop of at least 6 of the 7 P2X receptors. We used
      alanine replacement mutagenesis to determine the effects of individual conserved
      aromatic residues on the properties of human P2X(1) receptors expressed in
      Xenopus oocytes. ATP evoked concentration-dependent (EC(50) approximately 1
      microm) desensitizing currents at wild-type receptors and for the majority of
      mutants there was no change (10 residues) or a <6-fold decrease in ATP potency (6
      mutants). Mutants F195A and W259A failed to form detectable channels at the cell
      surface. F185A and F291A produced 10- and 160-fold decreases in ATP potency. The
      partial agonists 2',3'-O-(4-benzoyl)-ATP (BzATP) and P(1),P(5)-di(adenosine 5')
      pentaphosphate (Ap(5)A) were tested on a range of mutants that decreased ATP
      potency to determine whether this resulted predominantly from changes in agonist
      binding or gating of the channel. At K68A and K309A receptors BzATP and Ap(5)A
      had essentially no agonist activity but antagonized, or for R292A potentiated,
      ATP responses. At F185A receptors BzATP was an antagonist but Ap(5)A no longer
      showed affinity for the receptor. These results suggest that residues Lys-68, Phe
      185, Phe-291, Arg-292, and Lys-309 contribute to ligand binding at P2X(1)
      receptors, with Phe-185 and Phe-291 coordinating the binding of the adenine ring
      of ATP.

PMID- 14699169
TI  - Editorial comment--cerebral near-infrared spectroscopy: how far away from a
      routine diagnostic tool?